PMID- 27863337
TI  - Lead accumulation and metallothionein content in female rats of different ages
      and generations after daily intake of Pb-contaminated food.
AB  - Female Wistar rats of different ages (45, 90 and 140 days) and generations
      (mothers and offspring) were fed a feed containing 2.0mg of Pb kg-1 daily from
      weaning and the Pb accumulation was determined in different organs and in
      maternal milk, in addition metallothioneins (MTs) content was determined in the
      liver and kidneys. The results showed that Pb accumulation exhibited the
      following pattern: bone>liver>kidney>gut>blood cells>muscle>brain>ovary. Bones
      accumulated the most Pb in all animals, with its concentration increasing with
      age and prenatal exposure. Pb accumulation in the liver, kidney and blood cells,
      did not follow a consistent pattern with increasing age and our data did not
      indicate a relationship between the presence of MTs in liver and kidney and metal
      accumulation in these organs. However, in the offspring and with increasing age,
      Pb accumulated in more organs. Mothers fed with Pb produced contaminated milk,
      exposing their offspring to the metal via nursing Thus, increasing age and
      prenatal exposure increases susceptibility to Pb toxicity-induced damage.

PMID- 27863336
TI  - A potentially protective role of IL-18 Binding Protein in HIV-infected Long-Term
      Non-Progressors.
AB  - An imbalance between IL-18 and its antagonist, IL-18 Binding Protein, occurs in
      the circulation of HIV-infected individuals. We show here for the first time that
      HIV-infected Long Term Non-Progressors (LTNPs) do not develop this imbalance, and
      maintain normal levels of IL-18BP in the circulation. Their circulating levels of
      the antagonist correlate negatively with viral loads and show a positive trend
      with CD4+ T cells counts. The maintenance of normal production of IL-18BP may
      contribute, at least in part, to the ability of LTNPs to delay AIDS progression.

PMID- 27863338
TI  - Improved building up a model of toxicity towards Pimephales promelas by the Monte
      Carlo method.
AB  - By optimization of so-called correlation weights of attributes of simplified
      molecular input-line entry system (SMILES) quantitative structure - activity
      relationships (QSAR) for toxicity towards Pimephales promelas are established. A
      new SMILES attribute has been utilized in this work. This attribute is a
      molecular descriptor, which reflects (i) presence of different kinds of bonds
      (double, triple, and stereo chemical bonds); (ii) presence of nitrogen, oxygen,
      sulphur, and phosphorus atoms; and (iii) presence of fluorine, chlorine, bromine,
      and iodine atoms. The statistical characteristics of the best model are the
      following: n=226, r2=0.7630, RMSE=0.654 (training set); n=114, r2=0.7024,
      RMSE=0.766 (calibration set); n=226, r2=0.6292, RMSE=0.870 (validation set). A
      new criterion to select a preferable split into the training and validation sets
      are suggested and discussed.

PMID- 27863339
TI  - Classifying injury narratives of large administrative databases for surveillance
      A practical approach combining machine learning ensembles and human review.
AB  - Injury narratives are now available real time and include useful information for
      injury surveillance and prevention. However, manual classification of the cause
      or events leading to injury found in large batches of narratives, such as workers
      compensation claims databases, can be prohibitive. In this study we compare the
      utility of four machine learning algorithms (Naive Bayes, Single word and Bi-gram
      models, Support Vector Machine and Logistic Regression) for classifying
      narratives into Bureau of Labor Statistics Occupational Injury and Illness event
      leading to injury classifications for a large workers compensation database.
      These algorithms are known to do well classifying narrative text and are fairly
      easy to implement with off-the-shelf software packages such as Python. We propose
      human-machine learning ensemble approaches which maximize the power and accuracy
      of the algorithms for machine-assigned codes and allow for strategic filtering of
      rare, emerging or ambiguous narratives for manual review. We compare human
      machine approaches based on filtering on the prediction strength of the
      classifier vs. agreement between algorithms. Regularized Logistic Regression (LR)
      was the best performing algorithm alone. Using this algorithm and filtering out
      the bottom 30% of predictions for manual review resulted in high accuracy
      (overall sensitivity/positive predictive value of 0.89) of the final machine
      human coded dataset. The best pairings of algorithms included Naive Bayes with
      Support Vector Machine whereby the triple ensemble NBSW=NBBI-GRAM=SVM had very
      high performance (0.93 overall sensitivity/positive predictive value and high
      accuracy (i.e. high sensitivity and positive predictive values)) across both
      large and small categories leaving 41% of the narratives for manual review.
      Integrating LR into this ensemble mix improved performance only slightly. For
      large administrative datasets we propose incorporation of methods based on human
      machine pairings such as we have done here, utilizing readily-available off-the
      shelf machine learning techniques and resulting in only a fraction of narratives
      that require manual review. Human-machine ensemble methods are likely to improve
      performance over total manual coding.

PMID- 27863340
TI  - Solder joint failure localization of welded joint based on acoustic emission
      beamforming.
AB  - A localization approach of welded joint damage is proposed based on acoustic
      emission (AE) beamforming. In this method, a uniform line array is introduced to
      detect the AE signal of welded joints in specified area. In order to investigate
      the influence of fillet and crimping commonly existing in a welded plate
      structure during the AE wave propagation process, the finite element method (FEM)
      is applied to simulate the behavior of AE wave in the specimen. The simulation
      localization results indicate that the proposed localization approach can
      effectively localize AE sources although there exist the fillet and crimping, and
      it is also validated by the pencil-lead-broken test on rectangular steel tube
      with welded joints. Finally, the proposed method is adopted to localize the
      failure of solder joint in operation vibration condition. The proposed method is
      successful to localize the compact AE source caused by the cracked joint based on
      wavelet packet transform.

PMID- 27863341
TI  - Physical constraints on the non-dimensional absorption coefficients of
      compressional and shear waves for viscoelastic cylinders.
AB  - BACKGROUND: Normalized absorption coefficients for the longitudinal and shear
      waves in viscoelastic (polymer-type) materials, extracted from non-fictional
      experimental data showed anomalous effects, such as the generation of a negative
      radiation force (NRF) in plane progressive waves, negative energy absorption and
      extinction efficiencies and a scattering enhancement, not in agreement with
      energy conservation. OBJECTIVE: The objective of this work is directed towards
      analyzing those anomalies from the standpoint of energy conservation. Physical
      conditions which demonstrate that the ratio of the normalized absorption
      coefficients cannot be of arbitrary value but depends on the ratio of the square
      of the compressional and shear wave speeds, are established and discussed.
      METHOD: The necessary physical condition for the validity of the linear
      viscoelastic (VE) model for any passive (i.e. that does not generate energy)
      polymeric cylinder with an ultrasonic absorption of hysteresis-type submerged in
      a non-viscous fluid requires that the absorption efficiency be positive (Qabs>0)
      since there are no active radiating sources inside the core material. This
      condition imposes restrictions on the values attributed to the normalized
      absorption coefficients for the compressional and shear-wave wavenumbers for each
      partial-wave mode n. The forbidden values produce anomalous/unphysical NRF,
      negative absorption and extinction efficiencies, as well as an enhancement of the
      scattering efficiency using plane progressive waves, not in agreement with energy
      conservation. RESULTS: Based on the partial wave series expansion method in
      cylindrical coordinates, numerical results for the radiation force, extinction,
      absorption and scattering energy efficiencies assuming plane progressive wave
      incidence are performed for three VE polymer cylinders immersed in a non-viscous
      host liquid (i.e. water) with particular emphasis on the shear-wave absorption
      coefficient, the dimensionless size parameter ka (where k is the wavenumber and a
      is the radius of the cylinder) and the partial-wave mode number n. Physical and
      mathematical conditions are established for the non-dimensional absorption
      coefficients of the longitudinal and shear waves for a cylinder (i.e. the 2D
      case) in terms of the sound velocities in the VE material. The physical condition
      for the spherical 3D case is also noted. CONCLUSION: For passive materials, the
      physical conditions must be always satisfied to allow accurate computations of
      the acoustic radiation force, torque, and energy absorption, extinction and
      scattering efficiencies for VE cylinders having a hysteresis type of absorption
      (such as polymers and plastics), and submerged in a non-viscous fluid. The
      physical conditions must be always satisfied regardless of the shape of the
      incident field. They also serve to validate and verify experimental data for VE
      materials and test the accuracy of related numerical computations.

PMID- 27863342
TI  - A case report describing diverticulosis of the appendix presenting as acute
      appendicitis.
AB  - INTRODUCTION: Diverticulosis of the appendix (DA) is a rare clinical finding
      which is often confused with acute or chronic appendicitis and is usually only
      identified during or after appendectomy. The symptoms of DA can last for up to
      two weeks and laboratory studies tend to reflect a more chronic inflammation.
      Distinguishing the two entities is important as DA has a higher risk for
      perforation and may be associated with an underlying malignancy. PRESENTATION OF
      CASE: A 54--year old African--American male presented with three--days of right
      sided abdominal pain, nausea, and vomiting. Physical exam and abdominal CT
      imaging were concerning for early acute appendicitis. The patient was taken
      emergently to the operating room for laparoscopic appendectomy. Extensive
      adhesions were found around the Appendix which was grossly abnormal with multiple
      diverticula. The patient had an uneventful recovery. DISCUSSION: Patients with DA
      are often misdiagnosed with chronic or acute appendicitis based on their
      presenting symptoms and imaging. While appendectomy is the definitive treatment,
      diagnosing DA before surgery is important in determining the patient's risks and
      potential complications. CONCLUSION: Diverticulosis of the Appendix is a rare
      clinical entity which is often misdiagnosed. Better imaging techniques and higher
      indices of clinical suspicion are needed to make the appropriate diagnoses before
      patients are taken for surgery.

PMID- 27863343
TI  - Acrometastasis following colorectal cancer: A case report and review of
      literature.
AB  - INTRODUCTION: Colorectal cancer commonly metastasises to the liver, peritoneum
      and lungs. Bony metastases are uncommon in colorectal cancer and in particular
      metastases to the hands or feet (acrometastasis) are an extremely rare
      occurrence. CASE PRESENTATION: A 65-year-old male with a colonic malignancy
      underwent elective anterior resection. Intra-operatively he was found to have a
      pelvic collection necessitating an end colostomy. Histology confirmed complete
      Dukes B tumour excision with no evidence of lymph node metastases. The patient
      underwent chemo-radiotherapy but was unsuitable for reversal of Hartmann's due to
      elevated CEA levels and asymmetrical thickening of the rectal stump with a
      solitary lung nodule identified at a one-year surveillance CT. The lung nodule
      was resected revealing metastatic adenocarcinoma and biopsies from the rectal
      stump showed chronic inflammatory changes. The patient was offered further
      chemotherapy. However, six years after his original surgery the patient presented
      with an acutely painful left foot with radiographic appearances of an
      infiltrative sclerotic and lucent lesion confirmed as a calcaneal acrometastasis
      on Magnetic Resonance Imaging (MRI). DISCUSSION: Diagnosis of acrometastasis is
      challenging and generally constitutes a wider metastatic process with poor
      prognosis. Patients are often asymptomatic or present with symptoms mimicking
      benign lesions such as arthritis, infection or ligamentous sprains of the hands
      or feet. Therefore, there should be a high index of suspicion and prompt
      radiological investigation is warranted in order to exclude disease recurrence.
      CONCLUSION: Although acrometastasis may indicate a poor prognosis, timely
      diagnosis and intervention may facilitate improvement of long-term survival and
      symptomatic management.

PMID- 27863344
TI  - Selection criteria limit generalizability of smoking pharmacotherapy studies
      differentially across clinical trials and laboratory studies: A systematic review
      on varenicline.
AB  - BACKGROUND: The selection criteria used in clinical trials for smoking cessation
      and in laboratory studies that seek to understand mechanisms responsible for
      treatment outcomes may limit their generalizability to one another and to the
      general population. METHODS: We reviewed studies on varenicline versus placebo
      and compared eligibility criteria and participant characteristics of clinical
      trials (N=23) and laboratory studies (N=22) across study type and to nationally
      representative survey data on adult, daily USA smokers (2014 National Health
      Interview Survey; 2014 National Survey on Drug Use and Health). RESULTS: Relative
      to laboratory studies, clinical trials more commonly reported excluding smokers
      who were unmotivated to quit and for specific medical conditions (e.g.,
      cardiovascular disease, COPD), although both study types frequently reported
      excluding for general medical or psychiatric reasons. Laboratory versus clinical
      samples smoked less, had lower nicotine dependence, were younger, and more
      homogeneous with respect to smoking level and nicotine dependence. Application of
      common eligibility criteria to national survey data resulted in considerable
      elimination of the daily-smoking population for both clinical trials (>=47%) and
      laboratory studies (>=39%). Relative to the target population, studies in this
      review recruited participants who smoked considerably more and had a later
      smoking onset age, and were under-representative of Caucasians. CONCLUSIONS:
      Results suggest that selection criteria of varenicline studies limit
      generalizability in meaningful ways, and differences in criteria across study
      type may undermine efforts at translational research. Recommendations for
      improvements in participant selection and reporting standards are discussed.

PMID- 27863345
TI  - Suppression of TNF-alpha and free radicals reduces systematic inflammatory and
      metabolic disorders: Radioprotective effects of ginseng oligopeptides on
      intestinal barrier function and antioxidant defense.
AB  - Irradiation therapy is markedly associated with intestinal injure and oxidant
      stress. This study aimed to investigate the effects of ginseng (Panax ginseng
      C.A. Mey.) oligopeptides (GOP) on irradiation-induced intestinal injury and
      antioxidant defense in mice. BALB/c mice (8 weeks old) were randomly divided into
      six groups: vehicle control, irradiation control (IR), IR+whey protein [0.30 g/kg
      body weight (BW)], IR+GOP 0.15 g/kg BW, IR+GOP 0.30 g/kg BW and IR+GOP 0.60 g/kg
      BW. Postirradiation 30-day survival trial, white blood cells count and bone
      marrow hematopoietic system damage were performed to identify the injury degree
      induced by irradiation. Then, histopathology analysis was observed and intestinal
      permeability in vivo was quantified with fluorescein isothiocyanate-dextran. The
      enzyme-linked immunosorbent assay was used to determine antioxidant ability,
      plasma inflammatory cytokines, diamine oxidase (DAO) and endotoxin (LPS) levels.
      The immunohistochemistry assay was used to analyze the expression levels of tight
      junction proteins. We found that GOP-treated mice exhibited lower concentrations
      of plasma LPS and DAO and decreased instructors of inflammatory and oxidative
      stress which were linked to the lower intestinal permeability and higher tight
      junction proteins expression. The blockage of GOP was linked with the reduction
      of TNF-alpha and free radicals. The 15-day pretreatment of GOP could exhibit
      radioprotective effects, and another 15-day posttreatment benefited the quick
      repair of irradiation-induced injury. We confirm that GOP would exhibit effective
      therapeutic value on attenuating irradiation-induced hematopoietic,
      gastrointestinal and oxidative injury in cancer patients.

PMID- 27863346
TI  - A diet-induced Sprague-Dawley rat model of nonalcoholic steatohepatitis-related
      cirrhosis.
AB  - Certain modified diets containing saturated fatty acids, cholesterol or fructose
      lead to the development of nonalcoholic steatohepatitis (NASH)-related fibrosis
      in rodents; however, progression to cirrhosis is rare. Experimental liver
      cirrhosis models have relied on genetic manipulation or administration of
      hepatotoxins. This study aimed to establish a reliable dietary model of NASH
      related cirrhosis in a relatively short period. Male Sprague-Dawley rats (9 weeks
      of age) were randomly assigned to normal, high-fat (HF), or two types (1.25% or
      2.5% cholesterol) of high-fat and high-cholesterol (HFC) diets for 18 weeks. All
      HFC diets contained 2% cholic acid by weight. Histopathological analysis revealed
      that the HFC diets induced obvious hepatic steatosis, inflammation with
      hepatocyte ballooning and advanced fibrosis (stage 3-4) in all 12 rats at 27
      weeks of age. In contrast, all five rats given the HF diet developed mild
      steatosis and inflammation without fibrosis. The amount of cholesterol in the
      liver and hepatocellular mitochondrial and microsomal fractions was significantly
      higher in rats fed the HFC diets than the normal or HF diets. The HFC diets
      significantly suppressed mRNA levels of microsomal triglyceride transfer protein,
      adenosine triphosphate binding cassette transporter G5, bile acid CoA: amino acid
      N-acyltransferase and bile salt export pump, as well as the enzymatic activity of
      carnitine palmitoyltransferase in the liver. In conclusion, the HFC diets induced
      liver cirrhosis in conjunction with hepatic features of NASH in Sprague-Dawley
      rats within 18 weeks, and altered gene expression and enzyme activity to
      accumulate lipid and bile acid in the liver.

PMID- 27863347
TI  - Preventive effects of Goji berry on dextran-sulfate-sodium-induced colitis in
      mice.
AB  - Goji berry (Lycium barbarum) exerts immune modulation and suppresses inflammation
      in vitro and in vivo. We hypothesized that Goji berry had beneficial effects on
      dextran sulfate sodium (DSS)-induced colitis in C57BL/6 mice through suppressing
      inflammation. Six-week-old male C57BL/6 mice were supplemented with a standard
      AIN-93G diet with or without 1% (w/w) Goji berry for 4 weeks. Then, colitis was
      induced by supplementing 3% DSS in drinking water for 7 days, followed by 7 days
      of remission period to mimic ulcerative colitis symptoms. Goji berry
      supplementation ameliorated DSS-induced body weight loss, diminished diarrhea and
      gross bleeding, and resulted in a significantly decreased disease activity index,
      as well as DSS-associated colon shortening. Moreover, 30% mortality rate caused
      by DSS-induced colitis was avoided because of Goji berry supplementation.
      Histologically, Goji berry ameliorated colonic edema, mucosal damage and
      neutrophil infiltration into colonic intestinal tissue in response to DSS
      challenge, which was associated with decreased expression of chemokine (C-X-C
      motif) ligand 1 and monocyte chemoattractant protein-1, as well as inflammatory
      mediators interleukin-6 and cyclooxygenase-2. In conclusion, Goji supplementation
      confers protective effects against DSS-induced colitis, which is associated with
      decreased neutrophil infiltration and suppressed inflammation. Thus, dietary Goji
      is likely beneficial to inflammatory bowel disease patients as a complementary
      therapeutic strategy.

PMID- 27863348
TI  - Outpatient follow-up during the first year after heart transplantation, is it
      feasible?
AB  - INTRODUCTION: First year follow-up after heart transplantation requires invasive
      tests. Although patients used to be hospitalized for this purpose, ambulatory
      invasive procedures now offer the possibility of outpatient follow-up. The
      feasibility and security of this strategy is unknown. METHODS: From 2007 we
      transitioned to outpatient follow-up. We have retrospectively reviewed the
      clinical course of the outpatient group (2007 to 2014) and an inpatient group
      (2000-2006). Basal characteristics, hospital stay, infections, rejection episodes
      and vascular complications were evaluated. RESULTS: 87 patients had Inpatient
      Follow-up (IF) and 98 Outpatient Follow-up (OF). Basal characteristics were
      similar, with significant differences in immunosuppression (tacrolimus IF 44.8%
      vs. OF 90.8%, and mycophenolate IF 86.2% vs OF 100%, both p values <0.001) and
      age (IF 52+/-11.5years vs. OF 56.1+/-11years, p=0.016). In the OF group more
      clinical visits were performed (IF 10 vs. OF 13, p<0.001) while hospital stay was
      lower (IF 23days vs. OF 3days, p<0.001). The rate of infection, rejection, and
      vascular complications was similar. No difference was found in 1-year mortality
      (IF 2.3% vs. 1.0%, p=0.60). CONCLUSION: First year post-cardiac transplantation
      outpatient follow-up seems to be feasible and safe in terms of infection,
      rejection, vascular complications and mortality.

PMID- 27863349
TI  - TRPV1 channels in cardiovascular system: A double edged sword?
AB  - Apart from modulating nociception, there is vital role of TRPV1 channels in
      modulating atherosclerosis, congestive heart failure, systemic hypertension,
      pulmonary hypertension, hemorrhagic shock and vascular remodeling. TRPV1 channel
      activation has shielding effect against the development of atherosclerosis and
      systemic hypertension. TRPV1 channel activation alleviates the formation of
      atherosclerotic lesions via increasing the expression of cholesterol efflux
      regulatory protein, UCP 2 and enhancing autophagy. Furthermore, activation of
      these channels enhances Na+ excretion and NO release to reduce the blood
      pressure. TRPV1 channel activation in the cardiac sensory neurons and subsequent
      CGRP release reduces ischemia-reperfusion injury. Activation of these channels
      during conditioning enhances CGRP and SP release from the sensory nerve fibers
      innervating the heart to induce cardioprotection. However, activation of these
      channels may elicit detrimental effects in pulmonary hypertension, hemorrhage and
      vascular remodeling. Activation of TRPV1 channels enhances smooth muscle cell
      proliferation to promote pulmonary hypertension. Moreover, TRPV1 channel
      inhibition reduces massive catecholamine release, improves survival during
      hemorrhage. Activation of these channels enhances vascular remodeling via
      enhancing NO release. Furthermore, dual role of TRPV1 channels has been reported
      in the perpetuation of congestive heart failure. On one hand, TRPV1 channel
      activation increases the expression of UCP2, PPAR- delta and mitochondrial
      sirtuin 3 to decrease oxidative stress and reduce heart injury. On the other
      hand, activation of these channels may enhance the expression of hypertrophic
      fibrotic proteins viz. GATA4, MMP to promote cardiac fibrosis. The present review
      discusses the dual role of activation of TRPV1 channels in diseases associated
      with cardiovascular system.

PMID- 27863350
TI  - Arterial calcification: A new perspective?
AB  - Arterial calcification is commonly seen in atherosclerosis, chronic kidney
      disease (CKD) and diabetes and has long been considered a natural progression of
      atherosclerosis. Yet it is a systemic condition, occurring in a wide and diverse
      range of disease states and no medical treatment for cardiovascular disease has
      yet found a way to regress it; on the contrary, lipid-lowering therapy may worsen
      its progression. Although numerous studies have found associations between
      calcification and biomarkers, none has yet found a unifying mechanism that
      explains the calcification found in atherosclerosis, CKD or diabetes and many of
      the biomarkers are equally associated with atheroma development and
      cardiovascular events. Furthermore, both presence and absence of coronary artery
      calcification appear predictive of plaque rupture and cardiovascular events,
      indicating that the association is not causal. This suggests that we are no
      further forward in understanding the true nature of arterial calcification or its
      pathogenesis, other than noting that it is 'multifactorial'. This is because most
      researchers view arterial calcification as a progressive pathological condition
      which must be treated. Instead, we hypothesise that calcification develops as an
      immune response to endothelial injury, such as shear stress or oxidative stress
      in diabetics, and is consequently part of the body's natural defences. This would
      explain why it has been found to be protective of plaque rupture and why it is
      unresponsive to lipid-lowering agents. We propose that instead of attempting to
      treat arterial calcification, we should instead be attempting to prevent or treat
      all causes of endothelial injury.

PMID- 27863351
TI  - Abnormal heart-rate response during cardiopulmonary exercise testing identifies
      cardiac dysfunction in symptomatic patients with non-obstructive coronary artery
      disease.
AB  - BACKGROUND: Symptomatic non-obstructive coronary artery disease is a growing
      clinical dilemma for which contemporary testing is proving to be of limited
      clinical utility. New methods are needed to identify cardiac dysfunction. METHODS
      AND RESULTS: This is a prospective observational cohort study conducted from
      December 2013 to August 2015 in two outpatient cardiology clinics (symptomatic
      cohort) and 24 outpatient practices throughout the US (healthy cohort) with
      centralized methodology and monitoring to compare heart-rate responses during
      cardiopulmonary exercise testing (CPET). Participants were 208 consecutive
      patients (median age, 61; range, 32-86years) with exercise intolerance and
      without prior heart or lung disease in whom coronary anatomy was defined and 116
      healthy subjects (median age, 45; range, 26-66years). Compared to stress ECG, the
      novel change in heart-rate as a function of work-rate parameter (DeltaHR-WR
      Slope) demonstrated significantly higher sensitivity to detect under-treated
      atherosclerosis with similar specificity. In men, area under the ROC curve
      increased from 60% to 94% for non-obstructive CAD and from 64% to 80% for
      obstructive CAD. In women, AUC increased from 64% to 85% for non-obstructive CAD
      and from 66% to 90% for obstructive CAD. DeltaHR-WR Slope correctly reclassified
      abnormal studies in the non-obstructive CAD group from 22% to 81%; in the
      obstructive CAD group from 18% to 84% and in the revascularization group from 35%
      to 78%. CONCLUSION: Abnormal heart-rate response during CPET is more effective
      than stress ECG for identifying under-treated atherosclerosis and may be of
      utility to identify cardiac dysfunction in symptomatic patients with normal
      routine cardiac testing.

PMID- 27863352
TI  - Ultrafiltration for acute decompensated cardiac failure: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Ultrafiltration is a method used to achieve diuresis in acute
      decompensated heart failure (ADHF) when there is diuretic resistance, but its
      efficacy in other settings is unclear. We therefore conducted a systematic review
      and meta-analysis to evaluate the use of ultrafiltration in ADHF. METHODS: We
      searched MEDLINE and EMBASE for studies that evaluated outcomes following
      filtration compared to diuretic therapy in ADHF. The outcomes of interest were
      body weight change, change in renal function, length of stay, frequency of
      rehospitalization, mortality and dependence on dialysis. We performed random
      effects meta-analyses to pool studies that evaluated the desired outcomes and
      assessed statistical heterogeneity using the I2 statistic. RESULTS: A total of 10
      trials with 857 participants (mean age 68years, 71% male) compared filtration to
      usual diuretic care in ADHF. Nine studies evaluated weight change following
      filtration and the pooled results suggest a decline in mean body weight -1.8; 95%
      CI, -4.68 to 0.97 kg. Pooled results showed no difference between the filtration
      and diuretic group in change in creatinine or estimated glomerular filtration
      rate. The pooled results suggest longer hospital stay with filtration (mean
      difference, 3.70; 95% CI, -3.39 to 10.80days) and a reduction in heart failure
      hospitalization (RR, 0.71; 95% CI, 0.51-1.00) and all-cause rehospitalization
      (RR, 0.89; 95% CI, 0.43-1.86) compared to the diuretic group. Filtration was
      associated with a non-significant greater risk of death compared to diuretic use
      (RR, 1.08; 95% CI, 0.77-1.52). CONCLUSIONS: There is insufficient evidence
      supporting routine use of ultrafiltration in acute decompensated heart failure.

PMID- 27863353
TI  - Association of increased serum CTRP5 levels with in-stent restenosis after
      coronary drug-eluting stent implantation: CTRP5 promoting inflammation, migration
      and proliferation in vascular smooth muscle cells.
AB  - BACKGROUND: We investigated whether serum level of C1q/TNF-related protein (CTRP)
      5 is associated with in-stent restenosis (ISR) after percutaneous coronary
      intervention (PCI) with drug-eluting stent (DES) implantation, and assessed the
      biological effects of CTRP5 in human aortic smooth muscle cells (hASMCs). METHODS
      AND RESULTS: Serum CTRP5 levels were assayed in 306 patients with and 306
      patients without angiographic ISR at approximately one year after DES-based PCI.
      Multivariate logistic regression analysis was performed to determine risk factors
      for ISR. Notably, serum CTRP5 levels were higher in ISR patients than in non-ISR
      counterparts (197+/-84ng/mL vs. 150+/-74ng/mL, P<0.001). Compared with the lowest
      tertile (<125ng/mL) of CTRP5, patients with the mid (125-200ng/mL) and the
      highest tertile (>200ng/mL) of CTRP5 had a more than 1.6-fold (adjusted OR=1.670
      2.127, P<=0.039) and 7.4-fold (adjusted OR=7.478-11.264, all P<0.001) increased
      risk of ISR (all P for trend <0.001), respectively, after adjustment for
      potential clinical, biochemical and angiographic characteristics. To assess the
      biological effects of CTRP5, we stimulated hASMCs with this protein. CTRP5
      concentration-dependently induced the expression of MMP-2, cyclin D1 and TNF
      alpha in hASMCs, with activation of Notch1, TGF-beta and hedgehog signaling
      pathways. Consistently, this protein promoted migration and proliferation of
      hASMCs in wound-healing, Boyden chamber and Brdu incorporation assay. CONCLUSION:
      Increased serum CTRP5 level is associated with ISR after PCI with DES
      implantation. CTRP5 promotes proliferation, inflammation and migration in
      vascular smooth muscle cells through activation of multiple pathways.

PMID- 27863354
TI  - Contrast media use in patients with chronic kidney disease undergoing coronary
      angiography: A systematic review and meta-analysis of randomized trials.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary
      angiography (CA), adequate hydration and minimizing volume of contrast media (CM)
      are class 1b recommendations for preventing contrast induced nephropathy (CIN).
      Current data are insufficient to justify specific recommendations about
      isoosmolar vs. low-osmolar contrast media by the ACCF/AHA/SCAI guidelines.
      METHODS: Randomized trials comparing IOCM to LOCM in CKD stage 3 and above
      patients undergoing CA, and reporting incidence of CIN (defined by a rise in
      creatinine of 25% from baseline) were included in the analysis. The secondary
      outcome of the study was the incidence of serum creatinine increase by >1mg/dl.
      RESULTS: A total of 2839 patients were included in 10 trials, in which 1430
      patients received IOCM and 1393 received LOCM. When compared to LOCM, IOCM was
      not associated with significant benefit in preventing CIN (OR=0.72, [CI: 0.50
      1.04], P=0.08, I2=59%). Subgroup analysis revealed non-significant difference in
      incidence of CIN based on baseline use of N-acetylcystine (NAC), diabetes status,
      ejection fraction, and whether percutaneous coronary intervention vs coronary
      angiography alone was performed. The difference between IOCM and LOCM was further
      attenuated when restricted to studies with larger sample size (>250 patients)
      (OR=0.93; [CI: 0.66-1.30]) or when compared with non-ionic LOCM (OR=0.79, [CI:
      0.52-1.21]). CONCLUSION: In patients with CKD stage 3 and above undergoing
      coronary angiography, use of IOCM showed overall non-significant difference in
      incidence of CIN compared to LOCM. The difference was further attenuated when
      IOCM was compared with non-ionic LOCM.

PMID- 27863355
TI  - Changes in the severity of aortic regurgitation at peak effort during exercise.
AB  - BACKGROUND: Chronic aortic regurgitation can be well tolerated for a long time.
      Some patients with normal ventricular function can even reach high levels of
      sporting performance. How the severity of regurgitation may change during
      exercise, however, is little known, although some studies suggest it diminishes.
      The present work examines, during exercise, the functional capacity, ventricular
      function, and regurgitation fraction (RF) in asymptomatic subjects with moderate
      or severe aortic regurgitation with preserved ejection fraction. METHODS: The
      study subjects (n=32; 23 men, 9 women) were patients referred to our
      echocardiography laboratory with moderate or severe aortic regurgitation,
      preserved left ventricular systolic function, and sinus rhythm into NYHA
      functional class I. All underwent transthoracic echocardiography at rest and at
      peak effort during an exercise protocol involving an inclined cycloergometer.
      Left atrial and ventricular volume indices were recorded, along with diastolic
      and systolic function, cardiac index, peripheral resistance, and RF. RESULTS: The
      mean age of the subjects was 43.8+/-18.2years; 59% suffered moderate
      regurgitation, 41% severe aortic regurgitation, and 84% had a dilated left
      ventricle. All subjects managed exercise loads adequate for their age. Peak
      effort was associated with a significant reduction (mean 44.5% [range 10-95%]) in
      the RF (21.8+/-13.2 vs. 39.3%+/-14.7% at rest; p=0.0001). The absolute reduction
      in the RF at peak effort was greater among the subjects with severe aortic
      regurgitation (21.2% vs. 13.3% in those with moderate regurgitation; p=0.018).
      CONCLUSIONS: The RF becomes smaller during exercise in asymptomatic subjects with
      moderate or severe aortic regurgitation and preserved ventricular function.

PMID- 27863356
TI  - Left ventricular assist devices and gastrointestinal evaluation: Results of a
      consecutive case series.
AB  - AIMS: To evaluate the benefit of preoperative gastrointestinal endoscopic
      evaluation in patients undergoing continuous flow left ventricular assist devices
      (CF-LVADs) implantation. METHODS AND RESULTS: A retrospective review of all fifty
      three patients undergoing CF-LVADs at West-German Heart and Vascular Center,
      University of Duisburg-Essen was performed. A routine preoperative
      esophagogastroduodenoscopy was performed in seven patients to assess
      gastrointestinal (GI) bleeding. None of the patients had GI bleeding at the time.
      All patients received HeartWare CF-LVAD (HVAD, HeartWare Inc., Framingham, MA,
      USA). Six of the patients had relevant endoscopic findings and received therapy
      accordingly. None of these patients developed GI bleeding in the first 30days
      after CF-LVAD implantation. CONCLUSION: Preoperative GI evaluation in patients
      undergoing elective CF-LVAD implantation might be beneficial in reducing GI
      bleeding postoperatively.

PMID- 27863357
TI  - Cardiovascular health among two ethnic groups living in the same region: A
      population-based study.
AB  - BACKGROUND: Poor cardiovascular health (CVH) among ethnic/racial minorities,
      studied primarily in the USA, may reflect lower access to healthcare. We examined
      factors associated with minority CVH in a setting of universal access to
      healthcare. METHODS AND RESULTS: CVH behaviors and factors were evaluated in a
      random population sample (551 Arabs, 553 Jews) stratified by sex, ethnicity and
      age. More Jews (10%) than Arabs (3%) had 3 ideal health behaviors. Only one
      participant had all four. Although ideal diet was rare (<=1.5%) across groups,
      Arabs were more likely to meet intake recommendations for whole grains, but less
      likely to meet intake recommendations for fruits/vegetables and fish. Arabs had
      lower odds of attaining ideal levels for body mass index and physical activity.
      Smoking prevalence was 57% among Arab men and 6% among Arab women. Having four
      ideal health factors (cholesterol, blood pressure, glucose, smoking) was observed
      in 2% and 8% of Arab and Jewish men, respectively, and 13% of Arab and Jewish
      women. Higher prevalence of ideal total-cholesterol corresponded to lower high
      density lipoprotein cholesterol among Arabs. No participant met ideal levels for
      all 7 metrics and only 1.8% presented with 6. Accounting for age and lower
      socioeconomic status, Arabs were less likely to meet a greater number of metric
      goals (odds ratio (95% confidence interval): 0.62 (0.42-0.92) for men, and 0.73
      (0.48-1.12) for women). CONCLUSIONS: Ideal CVH, rare altogether, was less
      prevalent among the Arab minority albeit universal access to healthcare. Health
      behaviors were the main contributors to the CVH disparity.

PMID- 27863358
TI  - Temporal trends and long term follow-up of implantable cardioverter defibrillator
      therapy for secondary prevention: A 15-year single-centre experience.
AB  - BACKGROUND: The aim of this study was to determine overall and aetiology-related
      incidence of secondary prevention ICD implantation over the last 15years in
      Canton Ticino and to assess clinical outcome according to time period of
      implantation. METHODS AND RESULTS: Consecutive patients treated by implantation
      of an ICD for secondary prevention from 2000 to 2015 were included in the current
      study and compared between 5-year cohorts (2000/2004; 2005/2009; 2010/2015).
      Yearly implantation rate, changing in clinical presentation over years and events
      during follow-up were evaluated. One-hundred fifty six patients were included.
      ICD implantation rate increased from 2.1 in 2000-2005 to 5.1 in 2010-2015,
      respectively (p 0.001). There was an increase in the proportion of non-ischaemic
      patients and of ventricular tachycardia (VT) as presenting rhythm. No differences
      in appropriate ICD interventions were observed according to aetiology, presenting
      arrhythmia or type of device. Reverse remodelling was observed more often in non
      ischaemic patients, without any influence on the occurrence of appropriate
      interventions. Previous myocardial infarction (MI), atrial fibrillation (AF),
      NYHA class 2-3 and left ventricular ejection fraction (LVEF)<35% were predictors
      of appropriate therapies during follow-up. CONCLUSIONS: Rate of implants for
      secondary prevention indication has almost doubled during the last 15years.
      Importantly, there has been a progressive increase of non-ischaemic patients
      receiving an ICD, and of VT as presenting rhythm. Patients had an overall good
      survival and a relatively low incidence of appropriate therapies. Improvement of
      ejection fraction did not correlate with risk reduction of ventricular
      arrhythmias.

PMID- 27863359
TI  - Is hyperhomocysteinemia a causal factor for heart failure? The impact of the
      functional variants of MTHFR and PON1 on ischemic and non-ischemic etiology.
AB  - BACKGROUND: Hyperhomocysteinemia was found to be uniformly associated with the
      development of heart failure (HF) and HF mortality; however, it is uncertain
      whether this relation is causative or not. We used Mendelian randomization to
      examine the associations of the methylene tetrahydrofolate gene (MTHFR) and
      paraoxonase 1 gene (PON1) variants as a proxy for lifelong exposure to high Hcy
      and Hcy-thiolactone concentrations with the development of HF in men aged
      <=60years and the occurrence of adverse effects at one-year follow-up. METHODS:
      The study enrolled 172 men with HF: 117 with ischemic etiology (iHF) related to
      coronary artery disease (CAD) and 55 with non-ischemic etiology (niHF) related to
      dilated cardiomyopathy (DCM). The reference group of 329 CAD patients without HF
      and the control group of 384 men were also analyzed. RESULTS:
      Hyperhomocysteinemia (OR=2.0, P<0.05) and the MTHFR 677TT/1298AA, 677CC/1298CC
      genotypes (OR=1.6, P=0.03) were associated with HF regardless of its etiology,
      especially among normotensives (OR=4.6, P=0.001 and OR=2.3, P=0.003,
      respectively). In niHF, the PON1 162AA (OR=2.3, P=0.03) and 575AG+GG (OR=0.46,
      P=0.01) genotypes also influenced the risk. The interaction between HDLC<1mmol/L
      and the PON1 575GG genotype was found to influence the risk of iHF (OR=7.2,
      P=0.009). Hyperhomocysteinemia improved the classification of niHF patients as
      'high-risk' by 10.1%. Ejection fraction <30% and DCM increased the probability of
      HF death or re-hospitalization within one year. CONCLUSION: Our results provide
      evidence that hyperhomocysteinemia is a causal factor for niHF in DCM, while
      dysfunctional HDL could contribute to the pathogenesis of iHF.

PMID- 27863360
TI  - The effect of beta-blockers on mortality in heart failure with preserved ejection
      fraction: A meta-analysis of observational cohort and randomized controlled
      studies.
AB  - BACKGROUND: Nearly half of patients with heart failure (HF) have preserved
      ejection fraction (EF) and the mortality of patients with HF with preserved EF
      (HFpEF) is high. However, there is no therapy to improve survival in HFpEF.
      Although observational cohort studies (OCSs) have examined the survival benefit
      of beta-blockers in HFpEF, the results are inconsistent due to limited power with
      small sample sizes and/or lack of adjustment for known confounders. Furthermore,
      recent randomized controlled trial (RCT)s failed to show the mortality benefit of
      beta-blockers in HFpEF. However, these RCTs were not adequately powered and thus
      the definite conclusion cannot be drawn. METHODS AND RESULTS: We aimed to conduct
      a meta-analysis of the effect of beta-blockers on mortality in HFpEF. The search
      of electronic databases identified 5 OCSs with propensity score (PS) analysis
      (12,315 patients), 6 OCSs without PS analysis (15,275 patients), and 3 RCTs (1046
      patients). Beta-blocker use was associated with improved survival in the pooled
      analysis of OCSs with PS analysis (RR [95% CI]=0.79 [0.66-0.95]) and in that of
      OCSs without PS analysis (0.70 [0.52-0.94]). In the pooled analysis of RCTs, beta
      blocker use was associated with non-significant reduced risk for mortality (RR
      [95% CI]=0.80 [0.61-1.05]). Overall, use of beta-blockers reduced the risk of
      mortality by 21% (RR [95% CI]=0.79 [0.71-0.88]). CONCLUSION: Our meta-analysis
      suggests the potential mortality benefit of beta-blockers in HFpEF. Well-designed
      and powered RCTs should be planned to confirm our observed potential survival
      benefit of beta-blockers in HFpEF.

PMID- 27863361
TI  - Transradial approach for coronary angiography and intervention in the elderly: A
      meta-analysis of 777,841 patients.
AB  - BACKGROUND: Studies showing an advantage of transradial approach (TR) for
      coronary angiography and intervention (PCI) compared to the transfemoral approach
      (TF) predominantly included a younger population. Therefore, we conducted a meta
      analysis of published studies to determine the efficacy of TR in the elderly
      population. METHODS AND RESULTS: A comprehensive search identified 16 studies [3
      randomized controlled studies, 13 observational] comprising 777,841 elderly
      patients undergoing PCI. TR was used in 99,201 patients and TF in 678,640
      patients. The results from observational studies showed that TR was associated
      with a lower rate of vascular complications (0.4% vs. 0.8%, OR 0.36, 95% CI 0.30
      0.44), stroke (0.3% vs. 0.4%, OR 0.81, 95% CI 0.66-1.0) and death (2.0% vs. 2.2%,
      OR 0.51, 95% CI 0.41-0.63). RCTs confirmed findings from observational studies
      for both significant reduction in vascular complications (2.7% vs. 7%, OR 0.37,
      95% CI 0.23-0.60) and stroke (0.4% vs. 1.4%, OR 0.31, 95% CI 0.10-0.97) but
      showed no effect on mortality (3.3% vs. 2.8%, OR 1.20, 95% CI 0.69-2.09).
      However, among patients with ST elevation myocardial infarction (STEMI), TR was
      associated with a mortality benefit (5% vs. 7%, OR 0.48, 95% CI 0.25-0.90,
      p=0.02). Access site crossover rate was higher for TR compared to the TF approach
      (11% vs. 3%, p=0.0003) but there was no difference in contrast media use,
      procedure duration, fluoroscopy time and door to balloon time for STEMI.
      CONCLUSION: TR for PCI in the elderly is associated with a reduced risk of
      stroke, lower rate of vascular complications overall and a mortality benefit for
      patients presenting with STEMI. The access site cross rate for TR is higher
      compared to TF but remains acceptably low. TR should be the preferred strategy
      for PCI in the elderly to optimize clinical benefit in this high-risk group.

PMID- 27863362
TI  - Comparison of cardiovascular risk assessment tools and their guidelines in
      evaluation of 10-year CVD risk and preventive recommendations: A population based
      study.
AB  - BACKGROUND: Identification of individuals at risk of cardiovascular diseases
      (CVDs) results in better clinical outcomes and may help policy makers in
      conscious decision making for community based and national intervention
      strategies. The main aim of this study was to compare various CVD risk assessment
      tools and their related guidelines in estimation of 10-year CVD risk and
      subsequent therapeutic recommendations, respectively. METHODS: Data of 3086
      subjects aged 40-74years from a cohort study of northern Iran were utilized in
      this cross-sectional study. The risks were calculated based on American College
      of Cardiology/American Heart Association (ACC/AHA) tool, two versions of
      Systematic Coronary Risk Evaluation (SCORE) equations (for low and high risk
      European countries) and Framingham approach. We also detected participants who
      ought to be recommended for treatment based on the specific guidelines related to
      each of the risk assessment tools. RESULTS: Mean cardiovascular risks were
      12.96%, 8.84%, 1.90% and 3.45% in men and 5.87%, 2.13%, 0.8% and 1.13% in women
      based on ACC/AHA, Framingham, SCORE equation for low-risk European countries and
      high-risk European countries, respectively. Based on ACC/AHA, Adult Treatment
      Panel III (ATPIII) and European Society of Cardiology (ESC) guidelines related to
      SCORE equations for low and high risk European countries 58.2%, 27.1%, 21.1% and
      28.6% of men and 39.7%, 33.0%, 29.5% and 30.7% of women were recommended to
      statin therapy, respectively. CONCLUSIONS: In conclusion, more individuals were
      recommended for treatment by ACC/AHA guideline than the other guidelines.

PMID- 27863363
TI  - Exercise-based cardiac rehabilitation in twelve European countries results of the
      European cardiac rehabilitation registry.
AB  - AIM: Results from EuroCaReD study should serve as a benchmark to improve
      guideline adherence and treatment quality of cardiac rehabilitation (CR) in
      Europe. METHODS AND RESULTS: Data from 2.054 CR patients in 12 European countries
      were derived from 69 centres. 76% were male. Indication for CR differed between
      countries being predominantly ACS in Switzerland (79%), Portugal (62%) and
      Germany (61%), elective PCI in Greece (37%), Austria (36%) and Spain (32%), and
      CABG in Croatia and Russia (36%). A minority of patients presented with chronic
      heart failure (4%). At CR start, most patients already were under medication
      according to current guidelines for the treatment of CV risk factors. A wide
      range of CR programme designs was found (duration 3 to 24weeks; total number of
      sessions 30 to 196). Patient programme adherence after admission was high (85%).
      With reservations that eCRF follow-up data exchange remained incomplete, patient
      CV risk profiles experienced only small improvements. CR success as defined by an
      increase of exercise capacity >25W was significantly higher in young patients and
      those who were employed. Results differed by countries. After CR only 9% of
      patients were admitted to a structured post-CR programme. CONCLUSIONS: Clinical
      characteristics of CR patients, indications and programmes in Europe are
      different. Guideline adherence is poor. Thus, patient selection and CR programme
      designs should become more evidence-based. Routine eCRF documentation of CR
      results throughout European countries was not sufficient in its first application
      because of incomplete data exchange. Therefore better adherence of CR centres to
      minimal routine clinical standards is requested.

PMID- 27863364
TI  - Interactions of digitalis and class-III antiarrhythmic drugs: Amiodarone versus
      dronedarone.
AB  - BACKGROUND: A post hoc analysis of the PALLAS trial suggested possible
      interactions of dronedarone and digitalis glycosides. The aim of the present
      study was to compare the effects dronedarone or amiodarone in combination with
      digitalis glycosides. METHODS AND RESULTS: Eleven female rabbits underwent
      chronic oral treatment with amiodarone (50mg/kg/d for 6weeks). Ten rabbits were
      treated with dronedarone (50mg/kg/d for 6weeks). Ten rabbits were used as
      controls. Hearts were isolated and Langendorff-perfused. Monophasic action
      potentials and ECG showed a moderate prolongation of QT interval and action
      potential duration (APD). Both drugs also increased effective refractory period.
      Additional application of ouabain (0.2MUM) resulted in a significant decrease of
      QT interval, APD, and ERP in all groups. Ventricular arrhythmias were induced by
      programmed ventricular stimulation and aggressive burst stimulation. Reproducible
      occurrence was defined as occurrence of at least 3 episodes. Under baseline
      conditions in control hearts, ventricular fibrillation (VF) was inducible in 1 of
      10 hearts (7 episodes). After the application of 0.2MUM ouabain, 4 of 10 control
      hearts were inducible (24 episodes). One of 10 dronedarone-pretreated hearts (3
      episodes) and 2 of 11 amiodarone-pretreated hearts (6 episodes) showed VF before
      ouabain infusion. After the application of 0.2MUM ouabain, 7 of 10 dronedarone
      pretreated hearts were inducible (73 episodes). By contrast, only 4 of 11
      amiodarone-pretreated hearts (13 episodes) showed VF. CONCLUSION: In the present
      study, additional treatment with ouabain resulted in an increased ventricular
      vulnerability in al study groups. Of note, chronically dronedarone-pretreated
      hearts were significantly more vulnerable than amiodarone-pretreated hearts.

PMID- 27863365
TI  - Preoperative evaluation of coronary artery fistula using dual-source computed
      tomography.
AB  - OBJECTIVES: To evaluate the efficacy of dual-source computed tomography (DSCT) in
      assessing the morphological features, quantitative features, and associated
      coronary artery lesions among patients with coronary artery fistula (CAF) before
      surgery. METHODS: We enrolled 34 patients with CAF that were morphologically and
      quantitatively analyzed by DSCT and compared the analyses with surgical results
      (reference standard). The associated coronary artery lesions were also assessed.
      RESULTS: By DSCT, we identified 15 patients (44.1%) with left-sided CAF, 9
      (26.5%) with right-sided CAF, and 10 (29.4%) with bilateral CAF; the left
      anterior descending coronary artery (50.0%) was most frequently involved.
      Drainage was most commonly in the main pulmonary artery (41.2%), and those with
      right-sided CAF had larger feeding coronary arteries and drainage sites than
      those with left-sided or bilateral CAF (p<0.05). All the morphological features
      presented by DSCT were confirmed at surgery. In the quantitative analysis of CAF,
      DSCT was as accurate as surgery (r=0.95-0.98, p<0.001), and it was able to
      evaluate associated lesions accurately, including arteriosclerotic plaques,
      coronary artery aneurysms, and myocardial bridges. The evaluation could be
      completed in a single scan, without requiring an increased radiation dose (mean
      ED=2.27+/-1.92mSv). CONCLUSIONS: DSCT is an alternative noninvasive imaging
      method that enables accurate assessment of morphological features, quantitative
      features, and associated coronary artery lesions in patients with CAF. It can be
      used to provide comprehensive information for determining surgical strategies.

PMID- 27863366
TI  - Early versus late thrombolysis in acute arterial occlusion of lower extremity.
AB  - BACKGROUND: Acute arterial occlusion in lower extremity is an urgent condition
      which occurs when there is an abrupt interruption of blood flow into an
      extremity. Reperfusion through early intervention can increase limb salvage and
      decrease mortality. There was no common agreement when is the best to start
      thrombolysis in treating acute arterial occlusion. This study was designed to
      study the efficacy of an early thrombolysis compared with a late thrombolysis.
      METHOD: We identified all patients discharged from the Gwangju Veterans hospital
      with a diagnosis of acute arterial occlusion between 2006 and 2014. 72 patients
      were eligible, and every patient had treated with catheter-directed thrombolysis
      on the day or 1day after admission. Among them, 42 patients had undergone an
      early thrombolysis (less than 7days after the onset of symptoms) and the other 30
      patients had undergone a late thrombolysis (more than 7days after the onset of
      symptoms). The primary outcome was amputation rate at 6months. The secondary
      outcomes were all cause mortality at 6months and increase of ankle brachial index
      (ABI). RESULTS: Amputation rate at 180days in the early thrombolysis group was
      7.1% as compared with 30% in the late thrombolysis group. All cause mortality at
      6months and increase of ABI were not different between two groups. In
      multivariable Cox-regression analysis, late thrombolysis was independent
      predictor of amputation at 6months. CONCLUSION: Early thrombolysis was superior
      in preventing amputation than late thrombolysis.

PMID- 27863367
TI  - Prescription pattern of Chinese herbal products for heart failure in Taiwan: A
      population-based study.
AB  - BACKGROUND: Certain Chinese herbal products (CHPs) may protect against the
      progression of heart failure (HF). However, there is a lack of research regarding
      the use of CHPs in patients with HF. The aims of this study were to analyze CHPs
      usage patterns in patients with HF and to identify the frequency and combination
      of CHPs most commonly used for HF. 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 (NHIRD) for the years 2000-2010 in Taiwan. CHP use and the top ten most
      frequently prescribed formulae and single herbs for treating HF were assessed,
      including total formulae number and average and frequency of prescriptions.
      Demographic characteristics, including sex and age at diagnosis of HF, were
      examined, together with existing comorbidities. RESULTS: The cohort included
      19,988 newly diagnosed AD patients, who were given CHP treatment for HF between
      2000 and 2010. Among them, female patients (53.3%) and those over 65years old
      (63.9%) were more likely to use CM. After adjusting for demographic factors, HF
      patients suffering from coronary artery disease (CAD) were more likely to seek
      traditional Chinese medicine (TCM) treatment than those with non-TCM users (57.6%
      vs. 52.6%). Zhi-Gan-Cao-Tang (4.07%) and Danshen (5.13%) were the most frequent
      formula CHP and single CHP prescribed by TCM practitioners for treating HF,
      respectively. CONCLUSION: Most people with HF who consumed CHPs used CHPs to
      supplement Yang-Qi, nourish the Ying-blood, and strengthen the heart spirit as
      complementary medicines to relieve HF-related symptoms, in addition to using
      standard anti-HF treatments. Further large-scale, randomized clinical trials are
      warranted in order to determine the effectiveness and safety of these herbal
      medicines.

PMID- 27863368
TI  - Clinical and echocardiographic course in tako-tsubo cardiomyopathy: Long-term
      follow-up from a multicenter study.
AB  - OBJECTIVES: To jointly describe clinical characteristics, ECG and
      echocardiographic findings, and adverse cardiovascular events in patients with
      tako-tsubo cardiomyopathy (TC) in the long-term. METHODS: Longitudinal
      multicenter study including retrospective analysis of clinical and ECG data, and
      follow-up evaluation with clinical interview, electrocardiogram and
      echocardiogram. RESULTS: Data from 66 cases of TC were available for analysis of
      clinical and adverse cardiovascular events, and 56 of them completed the follow
      up visit including electrocardiogram and echocardiogram. Most patients (97%) were
      asymptomatic or oligosymptomatic (NYHA I [58%] or II [39%], respectively) at
      follow-up (median time: 3.7 [1.8-6.6] years). The vast majority of individual QRS
      complex and repolarization abnormalities had disappeared (87% with no ECG
      abnormalities at follow-up). On echocardiography, left ventricular ejection
      fraction was >=50% in all patients (mean: 63+/-6%). Wall motion abnormalities
      were observed in 4 patients (7%; 3 with apical wall motion abnormalities and 1
      with mild global hypokinesia). Long-term outcomes were as follows: 4 deaths (6%),
      2 cardiovascular and 2 non-cardiovascular; no atrial fibrillation development; no
      stroke events; 5 acute recurrence events of TC (8%). Globally, 57 patients (86%)
      had a clinical course free from adverse cardiovascular events. CONCLUSIONS: After
      a long period following the admission event, patients discharged from TC remain
      asymptomatic or minimally symptomatic, and feature a low prevalence of both ECG
      and left ventricular wall motion abnormalities; moreover, the latter lead to a
      very mild impairment of ejection fraction. Among cardiovascular adverse events,
      recurrence of the TC event appears to play the most significant role.

PMID- 27863369
TI  - Occurrence of antibiotics in rural catchments.
AB  - The transfer of 23 antibiotics from domestic and hospital sources was
      investigated in two elementary river watersheds receiving wastewater treatment
      plant (WWTP) discharges, in relation with the hydrological cycle and seasonal
      conditions. Antibiotic concentrations in the effluent of a WWTP treating
      wastewaters from both hospital and domestic sources (18-12 850 ng L-1) were far
      higher than those from domestic sources exclusively (3-550 ng L-1). In rivers,
      upstream of the WWTP discharges, fluoroquinolones only were found at low
      concentrations (<=10 ng L-1). Their presence might be explained by transfer from
      contaminated agricultural fields located on the river banks. Immediately
      downstream of the WWTP discharge, antibiotic occurrence increased strongly with
      mean concentrations up to 1210 ng L-1 for ofloxacin and 100% detection
      frequencies for vancomycin, sulfamethoxazole, trimethoprim and three
      fluoroquinolones. Dilution processes during high-flow periods led to
      concentrations 14 times lower than during low-flow periods. Downstream of the
      discharge, the antibiotic dissipation rate from the water column was higher for
      fluoroquinolones, in relation with their high sorption upon suspended matter and
      sediment. Only five antibiotics (vancomycin and four fluoroquinolones
      ciprofloxacin, norfloxacin, ofloxacin and enoxacin) were partly distributed (11%
      36%) in the particulate phase. Downstream of the discharge, antibiotic contents
      in sediment ranged from 1700 to 3500 ng g-1 dry weight, fluoroquinolones
      accounting for 97% of the total.

PMID- 27863370
TI  - Novel tacrine-1,2,3-triazole hybrids: In vitro, in vivo biological evaluation and
      docking study of cholinesterase inhibitors.
AB  - A new series of tacrine-1,2,3-triazole hybrids were designed, synthesized, and
      evaluated as potent dual cholinesterase inhibitors. Most of synthesized compounds
      showed good in vitro inhibitory activities toward both acetylcholinesterase
      (AChE) and butyrylcholinesterase (BChE). Among them, 7-chloro-N-((1-(4
      methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9-amine
      (5l) was found to be the most potent anti-AChE derivative (IC50 = 0.521 MUM) and
      N-((1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,2,3,4-tetrahydroacridin-9
      amine (5j) demonstrated the best anti-BChE activity (IC50 = 0.055 MUM). In vivo
      studies of compound 5l in Morris water maze task confirmed memory improvement in
      scopolamine-induced impairment. Also, molecular modeling and kinetic studies
      showed that compounds 5l and 5j bound simultaneously to the peripheral anionic
      site (PAS) and catalytic sites (CS) of the AChE and BChE.

PMID- 27863371
TI  - Healthy me: A gender-specific program to address body image concerns and risk
      factors among preadolescents.
AB  - This study evaluated a gender-specific, school-based program to promote positive
      body image and address risk factors for body dissatisfaction. In total, 652
      children aged 8-10 years participated (335 intervention, 317 wait-list control).
      Children participated in four 60min sessions and a recap session at three months
      post-intervention. The broad content areas were body image, peer relationships,
      media awareness, healthy diet, and exercise. The activities and examples for each
      session were gender specific. The recap session was an overview of the four
      sessions. Assessment measures were completed at pre-intervention, post
      intervention, and after the recap. Boys and girls in the intervention
      demonstrated higher muscle esteem and vegetable intake at post-intervention,
      compared to children in the control condition. Boys and girls demonstrated higher
      body esteem, muscle esteem and fruit and vegetable intake at the recap. Boys in
      the intervention demonstrated less investment in masculine gender norms at post
      intervention and at recap.

PMID- 27863372
TI  - The fucosylated CD147 enhances the autophagy in epithelial ovarian cancer cells.
AB  - Autophagy is modulated by multiple factors including CD147, but little is know
      about the effects and mechanism by which the modification of CD147 by Lewis y
      antigen regulates autophagy of ovarian cancer cell. Here, we reported that Lewis
      y antigen can promote basic autophagy activity and restrain autophagic cell death
      in ovarian cancer cells. Furthermore, human whole genome expression profile
      microarrays and massage pathway analysis revealed that during early stages of
      autophagy in ovarian cancer cells with highly expressing Lewis y antigen,
      PI3K/Akt-mTOR activity was reduced, in contrast, the PI3K/Akt-mTOR signaling
      pathway was activated as the length of amino acid deprivation increased, which
      inhibited eIF4G2 expression, further decreased the transcription of autophagy
      related genes, suppressed autophagic cell death. we also elaborated that co
      regulates protein degradation in cells via the ubiquitin-proteasome system and
      the autophagy-lysosome pathway. These findings suggested that the modification of
      CD147 by Lewis y antigen enhanced the survival ability by promoting basic
      autophagy activity and restraining autophagic cell death in ovarian cancer , thus
      playing an important role in ovarian cancer malignant progression.

PMID- 27863373
TI  - Tumor-targeting adenovirus OBP-401 inhibits primary and metastatic tumor growth
      of triple-negative breast cancer in orthotopic nude-mouse models.
AB  - Our laboratory previously developed a highly-invasive, triple-negative breast
      cancer (TNBC) variant using serial orthotopic implantation of the human MDA-MB
      231 cell line in nude mice. The isolated variant was highly-invasive in the
      mammary gland and lymphatic channels and metastasized to lymph nodes in 10 of 12
      mice compared to 2 of 12 of the parental cell line. In the present study, the
      tumor-selective telomerase dependent OBP-401 adenovirus was injected
      intratumorally (i.t.) (1 * 108 PFU) when the high-metastatic MDA-MB-231 primary
      tumor expressing red fluorescent protein (MDA-MB-231-RFP) reached approximately
      500 mm3 (diameter; 10 mm). The mock-infected orthotopic primary tumor grew
      rapidly. After i.t. OBP-401 injection, the growth of the orthotopic tumors was
      arrested. Six weeks after implantation, the fluorescent area and fluorescence
      intensity showed no increase from the beginning of treatment. OBP-401 was then
      injected into high-metastatic MDA-MB-231-RFP primary orthotopic tumor growing in
      mice which already had developed metastasis within lymphatic ducts. All 7 of 7
      control mice subsequently developed lymph node metastasis. In contrast, none of 7
      mice which received OBP-401 had lymph node metastasis. Seven of 7 control mice
      also had gross lung metastasis. In contrast, none of the 7 mice which received
      OBP-401 had gross lung metastasis. Confocal laser microscopy imaging demonstrated
      that all control mice had diffuse lung metastases. In contrast, all 7 mice which
      received OBP-401 only had a few metastatic cells in the lung. OBP-401 treatment
      significantly extended survival of the treated mice.

PMID- 27863374
TI  - Magic year for multiple myeloma therapeutics: Key takeaways from the ASH 2015
      annual meeting.
AB  - Despite the availability of various anticancer agents, Multiple Myeloma (MM)
      remains incurable in most cases, along with high relapse rate in the patients
      treated with these agents. The year 2015 saw major advancements in our battle
      against multiple myeloma. In 2015, the U.S. Food and Drug Administration (FDA)
      approved three new therapies for multiple myeloma, namely Ixazomib (an oral
      proteasome inhibitor), Daratumumab and Elotuzumab (monoclonal antibodies against
      CD38 and SLAMF7 respectively). The purpose of this review is to provide a
      detailed analysis of these aforementioned breakthrough therapies and two other
      newer agents, Filanesib (kinesis spindle inhibitor) and selinexor (SINE
      inhibitor), presented at the 2015 annual meeting of American Society of
      Hematology (ASH). We also describe the role of agents targeting PD-1 axis and
      chimeric antigen receptor T (CAR-T) cells in the treatment of MM.

PMID- 27863375
TI  - H2O2 treatment or serum deprivation induces autophagy and apoptosis in naked mole
      rat skin fibroblasts by inhibiting the PI3K/Akt signaling pathway.
AB  - Naked mole-rats (NMR; Heterocephalus glaber) display extreme longevity and
      resistance to cancer. Here, we examined whether autophagy contributes to the
      longevity of NMRs by assessing the effects of the PI3K/Akt pathway inhibitor
      LY294002 and the autophagy inhibitor chloroquine (CQ) on autophagy and apoptosis
      in NMR skin fibroblasts. Serum starvation, H2O2 treatment, and LY294002 treatment
      all increased the LC3-II/LC3-I ratio and numbers of double-membraned
      autophagosomes and autophagic vacuoles, and decreased levels of p70S6K, p
      AktSer473, and p-AktThr308. By contrast, CQ treatment decreased p70S6K,
      AktSer473, and AktThr308 levels. The Bax/Bcl-2 ratio increased after 12 h of
      exposure to LY294002 or CQ. These data show that inhibiting the Akt pathway
      promotes autophagy and apoptosis in NMR skin fibroblasts. Furthermore, LY294002
      or CQ treatment decreased caspase-3, p53, and HIF1-alpha levels, suggesting that
      serum starvation or H2O2 treatment increase autophagy and apoptosis in NMR skin
      fibroblasts by inhibiting the PI3K/Akt pathway. CQ-induced inhibition of late
      autophagy stages also prevented Akt activation and induced apoptosis. Finally,
      the HIF-1alpha and p53 pathways were involved in serum starvation- or H2O2
      induced autophagy in NMR skin fibroblasts.

PMID- 27863376
TI  - CXCR4 increases in-vivo glioma perivascular invasion, and reduces radiation
      induced apoptosis: A genetic knockdown study.
AB  - Glioblastoma (GBM) is a highly invasive brain tumor. Perivascular invasion,
      autovascularization and vascular co-option occur throughout the disease and lead
      to tumor invasion and progression. The molecular basis for perivascular invasion,
      i.e., the interaction of glioma tumor cells with endothelial cells is not well
      characterized. Recent studies indicate that glioma cells have increased
      expression of CXCR4. We investigated the in-vivo role of CXCR4 in perivascular
      invasion of glioma cells using shRNA-mediated knock down of CXCR4. We show that
      primary cultures of human glioma stem cells HF2303 and mouse glioma GL26-Cit
      cells exhibit significant migration towards human (HBMVE) and mouse (MBVE) brain
      microvascular endothelial cells. Blocking CXCR4 on tumor cells with AMD3100 in
      vitro, inhibits migration of GL26-Cit and HF2303 toward MBVE and HBMVE cells.
      Additionally, genetic down regulation of CXCR4 in mouse glioma GL26-Cit cells
      inhibits their in-vitro migration towards MBVE cells; in an in-vivo intracranial
      mouse model, these cells display reduced tumor growth and perivascular invasion,
      leading to increased survival. Quantitative analysis of brain sections showed
      that CXCR4 knockdown tumors are less invasive. Lastly, we tested the effects of
      radiation on CXCR4 knock down GL26-Cit cells in an orthotopic brain tumor model.
      Radiation treatment increased apoptosis of CXCR4 downregulated tumor cells and
      prolonged median survival. In summary, our data suggest that CXCR4 signaling is
      critical for perivascular invasion of GBM cells and targeting this receptor makes
      tumors less invasive and more sensitive to radiation therapy. Combination of
      CXCR4 knock down and radiation treatment might improve the efficacy of GBM
      therapy.

PMID- 27863377
TI  - Variable patterns of ectopic mineralization in Enpp1asj-2J mice, a model for
      generalized arterial calcification of infancy.
AB  - Generalized arterial calcification of infancy (GACI) is an autosomal recessive
      disorder characterized by early onset of extensive mineralization of the
      cardiovascular system. The classical forms of GACI are caused by mutations in the
      ENPP1 gene, encoding a membrane-bound pyrophosphatase/phosphodiesterase that
      hydrolyzes ATP to AMP and inorganic pyrophosphate. The asj-2J mouse harboring a
      spontaneous mutation in the Enpp1 gene has been characterized as a model for
      GACI. These mutant mice develop ectopic mineralization in skin and vascular
      connective tissues as well as in cartilage and collagen-rich tendons and
      ligaments. This study examined in detail the temporal ectopic mineralization
      phenotype of connective tissues in this mouse model, utilizing a novel cryo
      histological method that does not require decalcification of bones. The wild
      type, heterozygous, and homozygous mice were administered fluorescent
      mineralization labels at 4 weeks (calcein), 10 weeks (alizarin complexone), and
      11 weeks of age (demeclocycline). Twenty-four hours later, outer ears, muzzle
      skin, trachea, aorta, shoulders, and vertebrae were collected from these mice and
      examined for progression of mineralization. The results revealed differential
      timeline for disease initiation and progression in various tissues of this mouse
      model. It also highlights the advantages of cryo-histological fluorescent imaging
      technique to study mineral deposition in mouse models of ectopic mineralization
      disorders.

PMID- 27863378
TI  - Aberrant localization of apoptosis protease activating factor-1 in lipid raft sub
      domains of diffuse large B cell lymphomas.
AB  - Resistance to chemotherapy remains a challenge in the clinical management of
      diffuse B cell lymphomas despite aggressive chemotherapy such as CHOP and
      monoclonal CD20. Here we provide evidence that the apoptosome adaptor protein,
      Apaf-1, is mislocalized in primary cells derived from patients with diffuse large
      B cell lymphomas (DLBCL). Whereas, the total expression of Apaf-1 did not change,
      its sub-cellular localization was significantly different in DLBCL, compared to T
      cell lymphomas as well as cells derived from reactive lymphadenopathy biopsies.
      As expected, Apaf-1 was detected in the cytosolic fractions of non-B cell
      lymphomas and non-cancerous tissues; however, in B cell derived lymphomas the
      protein was detected in membrane raft sub-domains rather than the cytosol.
      Disruption of lipid raft structures resulted in the redistribution of Apaf-1 to
      the cytosol and restored apoptosis sensitivity of DLBCL. Furthermore, we
      identified novel small molecule compounds that target DLBCL by promoting Apaf-1
      release form lipid rafts via mechanisms that involve an increase in intracellular
      reactive oxygen species production. Taken together, our results implicate Apaf-1
      mislocalization as a potential diagnostic and prognostic marker for DLBCL, and
      provide a novel therapeutic strategy for circumventing the drug refractory nature
      of this sub-class of B cell lymphoma.

PMID- 27863379
TI  - Targeted next generation sequencing identifies two novel mutations in SEPN1 in
      rigid spine muscular dystrophy 1.
AB  - Rigid spine muscular dystrophy 1 (RSMD1) is a neuromuscular disorder, manifested
      with poor axial muscle strength, scoliosis and neck weakness, and a variable
      degree of spinal rigidity with an early ventilatory insufficiency which can lead
      to death by respiratory failure. Mutations of SEPN1 gene are associated with
      autosomal recessive RSMD1. Here, we present a clinical molecular study of a
      Chinese proband with RSMD1. The proband is a 17 years old male, showing
      difficulty in feeding, delayed motor response, problem in running with frequent
      fall down, early onset respiratory insufficiency, general muscle weakness and
      rigid cervical spine. Muscle biopsy identified increased variability of fiber
      size with atrophic muscle cells consistent with non-specific myopathic changes.
      Proband's elder brother presented with same phenotype as the proband and died at
      the age of 15 years due to acute respiratory failure. Proband's father and mother
      are phenotypically normal. Targeted exome capture based next generation
      sequencing and Sanger sequencing identified that the proband was a compound
      heterozygote with two novel mutations in SEPN1 gene; a novel missense mutation
      (c.1384T>C; p.Sec462Arg) and a novel nonsense mutation (c.1525C>T; p.Gln509Ter),
      inherited from his father and mother respectively. These two mutations are co
      segregated with the disease phenotypes in the proband and was absent in normal
      healthy controls. Our present study expands the mutational spectrum of the SEPN1
      associated RSMD1.

PMID- 27863380
TI  - Arctigenin functions as a selective agonist of estrogen receptor beta to restrict
      mTORC1 activation and consequent Th17 differentiation.
AB  - Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby
      attenuate colitis in mice by down-regulating the activation of mechanistic target
      of rapamycin complex 1 (mTORC1). The present study was performed to address its
      underlying mechanism in view of estrogen receptor (ER). The specific antagonist
      PHTPP or siRNA of ERbeta largely diminished the inhibitory effect of arctigenin
      on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17
      polarization condition, suggesting that arctigenin functioned in an ERbeta
      dependent manner. Moreover, arctigenin was recognized to be an agonist of ERbeta,
      which could bind to ERbeta with a moderate affinity, promote dissociation of
      ERbeta/HSP90 complex and nuclear translocation and phosphorylation of ERbeta, and
      increase the transcription activity. Following activation of ERbeta, arctigenin
      inhibited the activity of mTORC1 by disruption of ERbeta-raptor-mTOR complex
      assembly. Deficiency of ERbeta markedly abolished arctigenin-mediated inhibition
      of Th17 cell differentiation. In colitis mice, the activation of ERbeta,
      inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by
      PHTPP treatment. In conclusion, ERbeta might be the target protein of arctigenin
      responsible for inhibition of mTORC1 activation and resultant prevention of Th17
      cell differentiation and colitis development.

PMID- 27863381
TI  - Probucol prevents atrial ion channel remodeling in an alloxan-induced diabetes
      rabbit model.
AB  - Diabetes mellitus (DM) increases the risk of developing atrial fibrillation (AF),
      but the molecular mechanisms of diabetes-induced atrial remodeling processes have
      not been fully characterized. The aim of this study was to examine the mechanisms
      underlying atrial ion channel remodeling in alloxan-induced diabetes model in
      rabbits. A total of 40 Japanese rabbits were randomly assigned to a control group
      (C), alloxan-induced diabetic group (DM), probucol-treated control group (Control
      P), and probucol-treated diabetic group (DM-P). Using whole-cell voltage-clamp
      techniques, ICa,L, INa and action potential durations (APDs) were measured in
      cardiomyocytes isolated from the left atria in the four groups, respectively. In
      the DM group, increased Ica,L and decreased INa currents were reflected in
      prolonged APD90 and APD50 values. These changes were reversed in the DM-P group.
      In conclusion, probucol cured AF by alleviating the ion channel remodeling of
      atrial myocytes in the setting of diabetes and the promising therapeutic
      potential of anti-oxidative compounds in the treatment of AF warrants further
      study.

PMID- 27863382
TI  - An early-screening biomarker of endometrial carcinoma: NGAL is associated with
      epithelio-mesenchymal transition.
AB  - Neutrophil gelatinase-associated lipocalin is currently one of the most
      interesting and enigmatic proteins involved in the development of malignancies.
      In this study, we found that the expression of neutrophil gelatinase-associated
      lipocalin was up-regulated in endometrial cancer tissues and cell lines,
      significantly increased in early-grade ones, suggesting it may serve as a
      biomarker for early-stage screening for endometrial carcinoma. Moreover,
      neutrophil gelatinase-associated lipocalin was up-regulated in Ishikawa cells
      under going epithelio-mesenchymal transition induced by epidermal growth factor
      (5 ng/ml). Up-regulation of neutrophil gelatinase-associated lipocalin may
      correlate with the down-regulation of E-cadherin expression, up-regulation of
      Vimentin expression, enhanced cell migration, invasion and proliferation, which
      are the typical hallmarks of epithelio-mesenchymal transition processes.
      Neutrophil gelatinase-associated lipocalin may play a dual role during
      tumorigenetic and developmental processes of endometrial carcinoma. These results
      suggested neutrophil gelatinase-associated lipocalin to be a potential molecular
      target in the early diagnosis and treatment of endometrial carcinoma. Further
      studies are warranted to clarify the molecular mechanisms behind the expression
      and function of neutrophil gelatinase-associated lipocalin and epithelio
      mesenchymal transition.

PMID- 27863383
TI  - Adipocytes secreted leptin is a pro-tumor factor for survival of multiple myeloma
      under chemotherapy.
AB  - Accumulating evidences have shown that adipokines secreted from adipocytes
      contributes to tumor development, especially leptin. However, underlying
      mechanisms remain unclear. This study aims to explore the effect of leptin on
      development and chemoresistance in multiple myeloma cells and the potential
      mechanism. Analysis of levels of adipokines including leptin and adiponectin in
      28 multiple myeloma patients identified significantly higher leptin compared with
      28 normal controls(P < 0.05), and leptin level was positively correlated with
      clinical stage, IgG, ER, and beta2MG. Next, by using co-culture system of myeloma
      and adipocytes, and pharmacologic enhancement of leptin, we found that increased
      growth of myeloma cells and reduced toxicity of bortezomib were best observed at
      50 ng/ml of leptin, along with increased expression of cyclinD1, Bcl-2 and
      decreased caspase-3 expression. We also found that phosphorylated AKT and STAT3
      but not the proteins expression reached peak after 1h and 6h treatment of leptin,
      respectively. By using AG490, an agent blocking the phosphorylation of AKT and
      ERK, the proliferation of myeloma cells was inhibited, as well as the
      phosphorylation of AKT and STAT3, even adding leptin. Taken together, our study
      demonstrated that up-regulated leptin could stimulate proliferation of myeloma
      and reduce the anti-tumor effect of chemotherapy possibly via activating AKT and
      STAT3 pathways, and leptin might be one of the potential therapeutic targets for
      treating myeloma.

PMID- 27863385
TI  - Gli1 promotes colorectal cancer metastasis in a Foxm1-dependent manner by
      activating EMT and PI3K-AKT signaling.
AB  - Colorectal cancer(CRC) is one of the most commonly diagnosed cancers in human
      beings and metastasis is the main death reason. Recently, Gli1 has been reported
      to be a key regulator of various cancer biologies and genes expressions. However,
      the detailed molecular mechanism of Gli1 in CRC metastasis remains largely
      unknown. In this study, we aimed to investigate the role of Gli1 in CRC
      metastasis. We used qRT-PCR, Immunohistochemistry and Western blot to test the
      expression levels of Gli1, Foxm1 and other target genes in the tissues and cells;
      Lentivirus stable transfection to change the expression levels of Gli1 and Foxm1;
      Wound-healing, cell invasion, migration assays and tail vein metastatic assay to
      test the role of Gli1 in CRC metastasis in vitro and vivo. We demonstrated that
      Gli1 was significantly overexpressed in colorectal cancer tissues and cells.
      Foxm1 level had a positive correlation with Gli1. Furthermore, we found that Gli1
      promotes colorectal cancer cells metastasis in a Foxm1-dependent manner by
      activating EMT and PI3K-AKT signaling. Thus, we proved that Gli1 plays important
      role in CRC metastasis and provided a new visual field on the therapy of CRC
      metastasis.

PMID- 27863384
TI  - A novel highly potent trivalent TGF-beta receptor trap inhibits early-stage
      tumorigenesis and tumor cell invasion in murine Pten-deficient prostate glands.
AB  - The effects of transforming growth factor beta (TGF-beta) signaling on prostate
      tumorigenesis has been shown to be strongly dependent on the stage of
      development, with TGF-beta functioning as a tumor suppressor in early stages of
      disease and as a promoter in later stages. To study in further detail the
      paradoxical tumor-suppressive and tumor-promoting roles of the TGF-beta pathway,
      we investigated the effect of systemic treatment with a TGF-beta inhibitor on
      early stages of prostate tumorigenesis. To ensure effective inhibition, we
      developed and employed a novel trivalent TGF-beta receptor trap, RER, comprised
      of domains derived from the TGF-beta type II and type III receptors. This trap
      was shown to completely block TbetaRII binding, to antagonize TGF-beta1 and TGF
      beta3 signaling in cultured epithelial cells at low picomolar concentrations, and
      it showed equal or better anti-TGF-beta activities than a pan TGF-beta
      neutralizing antibody and a TGF-beta receptor I kinase inhibitor in various
      prostate cancer cell lines. Systemic administration of RER inhibited prostate
      tumor cell proliferation as indicated by reduced Ki67 positive cells and invasion
      potential of tumor cells in high grade prostatic intraepithelial neoplasia (PIN)
      lesions in the prostate glands of Pten conditional null mice. These results
      provide evidence that TGF-beta acts as a promoter rather than a suppressor in the
      relatively early stages of this spontaneous prostate tumorigenesis model. Thus,
      inhibition of TGF-beta signaling in early stages of prostate cancer may be a
      novel therapeutic strategy to inhibit the progression as well as the metastatic
      potential in patients with prostate cancer.

PMID- 27863386
TI  - Prognostic and diagnostic potential of isocitrate dehydrogenase 1 in esophageal
      squamous cell carcinoma.
AB  - We aimed to investigate the pattern of expression and clinical significance of
      isocitrate dehydrogenase 1(IDH1) in esophageal squamous cell carcinoma (ESCC).
      The IDH1 expression was determined by quantitative real-time polymerase chain
      reaction, immunohistochemistry, and Western blot analysis using 38 pairs of
      frozen tissues. Enzyme-linked immunosorbent assay was employed to measure 67
      pairs of serum samples from patients and their controls to evaluate its
      diagnostic value. Immunohistochemistry analysis of 111 formalin-fixed paraffin
      embedded tissue samples was conducted for explaining its prognostic value. After
      shRNA transfection, CCK8 and clonal efficiency assays were carried on for
      verifying the function of IDH1 in vitro. Increased expression at mRNA (P < 0.001)
      and protein levels (immunohistochemistry: P < 0.001, Western blot analysis: P <
      0.001) were observed. Similarly, the IDH1 expression in serum from patients with
      ESCC was significantly upregulated relative to that from healthy controls (P <
      0.001). Kaplan-Meier curve indicated that IDH1 upregulation predicted worse
      overall survival (OS) and progression-free survival (PFS). Univariate and
      multivariate analyses identified IDH1 expression as an independent prognostic
      factor for OS and PFS. Furthermore, OD450 values and colony numbers were
      decreased in sh-IDH1 groups (all P < 0.05). In conclusion, IDH1 is upregulated in
      patients with ESCC and can be used as a good potential biomarker for diagnosis
      and prognosis.

PMID- 27863387
TI  - Aberrant overexpression of ADAR1 promotes gastric cancer progression by
      activating mTOR/p70S6K signaling.
AB  - ADAR1, one of adenosine deaminases acting on RNA, modulates RNA transcripts
      through converting adenosine (A) to inosine (I) by deamination. Emerging evidence
      has implicated that ADAR1 plays an important role in a few of human cancers,
      however, its expression and physiological significance in gastric cancer remain
      undefined. In the present study, we demonstrated that ADAR1 was frequently
      overexpressed in gastric cancer samples by quantitative real-time PCR analysis.
      In a gastric cancer tissue microarray, ADAR1 staining was closely correlated with
      tumor stage (P < 0.001) and N classification (P < 0.001). Functional analysis
      indicated that ADAR1 overexpression promoted cell proliferation and migration in
      vitro, whereas ADAR1 knockdown resulted in an opposite phenotypes. Furthermore,
      ADAR1 knockdown also inhibited tumorigenicity and lung metastasis potential of
      gastric cancer cells in nude mice models. Mechanistically, ADAR1 expression had a
      significant effect on phosphorylation level of mTOR, p70S kinase, and S6
      ribosomal protein, implying its involvement in the regulation of mTOR signaling
      pathway. We conclude that ADAR1 contributes to gastric cancer development and
      progression via activating mTOR/p70S6K/S6 ribosomal protein signaling axis. Our
      findings suggest that ADAR1 may be a valuable biomarker for GC diagnosis and
      prognosis and may represent a new novel therapeutic opportunities.

PMID- 27863388
TI  - Comprehensive analysis of aberrantly expressed profiles of lncRNAs and miRNAs
      with associated ceRNA network in muscle-invasive bladder cancer.
AB  - Although initially thought to be transcriptional noise, long noncoding RNAs
      (lncRNAs) are gaining increased attention in human cancers as its diversity
      function. At present, lncRNAs are regarded as the main part of competing
      endogenous RNA (ceRNA) network due to its regulation on protein-coding gene
      expression by acting as miRNA sponges. However, functional roles of lncRNA
      mediated ceRNAs in muscle-invasive bladder cancer remain unclear. To clarify
      relevant potential mechanisms, here we comprehensively compared the expression
      profiles of mRNAs, lncRNAs and miRNAs between 322 muscle-invasive bladder cancer
      tissues and 19 non-tumor bladder tissues, based on the Cancer Genome Atlas
      (TCGA). A total of 22 lncRNAs were identified as aberrantly expressed and had
      correlations with tumorigenesis and/or progression of muscle-invasive bladder
      cancer (|log2FoldChange| > 1.5, corrected P value < 0.01). 6 out of the 22
      dysregulated lncRNAs functioned as prognostic biomarkers for patients with muscle
      invasive bladder cancer according to the overall survival analysis (P value <
      0.05). Finally, a dysregulated lncRNA-associated ceRNA network was successfully
      constructed, which inculdes five muscle-invasive bladder cancer-specific lncRNAs,
      nine miRNAs and 32 mRNAs. In summary, our study identified novel lncRNAs as
      candidate prognostic biomarkers and potential therapeutic targets for muscle
      invasive bladder cancer, based on large-scale sample size. More importantly, the
      newly identified ceRNA network will be beneficial for improving the understanding
      of lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of muscle
      invasive bladder cancer.

PMID- 27863389
TI  - NT1721, a novel epidithiodiketopiperazine, exhibits potent in vitro and in vivo
      efficacy against acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is an aggressive malignancy characterized by
      heterogeneous genetic and epigenetic changes in hematopoietic progenitors that
      lead to abnormal self-renewal and proliferation. Despite high initial remission
      rates, prognosis remains poor for most AML patients, especially for those
      harboring internal tandem duplication (ITD) mutations in the fms-related tyrosine
      kinase-3 (FLT3). Here, we report that a novel epidithiodiketopiperazine, NT1721,
      potently decreased the cell viability of FLT3-ITD+ AML cell lines, displaying
      IC50 values in the low nanomolar range, while leaving normal CD34+ bone marrow
      cells largely unaffected. The IC50 values for NT1721 were significantly lower
      than those for clinically used AML drugs (i.e. cytarabine, sorafenib) in all
      tested AML cell lines regardless of their FLT3 mutation status. Moreover,
      combinations of NT1721 with sorafenib or cytarabine showed better antileukemic
      effects than the single agents in vitro. Combining cytarabine with NT1721 also
      attenuated the cytarabine-induced FLT3 ligand surge that has been linked to
      resistance to tyrosine kinase inhibitors. Mechanistically, NT1721 depleted DNA
      methyltransferase 1 (DNMT1) protein levels, leading to the re-expression of
      silenced tumor suppressor genes and apoptosis induction. NT1721 concomitantly
      decreased the expression of EZH2 and BMI1, two genes that are associated with the
      maintenance of leukemic stem/progenitor cells. In a systemic FLT3-ITD+ AML mouse
      model, treatment with NT1721 reduced tumor burdens by > 95% compared to the
      control and significantly increased survival times. Taken together, our results
      suggest that NT1721 may represent a promising novel agent for the treatment of
      AML.

PMID- 27863390
TI  - Suppression of hepatic stellate cell activation through downregulation of
      gremlin1 expression by the miR-23b/27b cluster.
AB  - The imbalance between transforming growth factor beta and bone morphogenetic
      protein 7 signaling pathways is a critical step in promoting hepatic stellate
      cell activation during hepatic fibrogenesis. Gremlin1 may impair the balance.
      Something remains unclear about the regulatory mechanisms of gremlin1 action on
      hepatic stellate cell activation and hepatic fibrosis. In the current study,
      gremlin1 overexpression promotes activation of hepatic stellate cells. Knockdown
      of gremlin1 with siRNAs suppresses hepatic stellate cell activation and
      attenuates hepatic fibrosis in rat model. Our results also show that miR-23b/27b
      cluster members bind to 3'-untranslated region of gremlin1 resulting in reduction
      of transforming growth factor beta, alpha-smooth muscle actin and collagenI
      alpha1/2 gene expression. Our findings suggest that gremlin1 promotes hepatic
      stellate cell activation and hepatic fibrogenesis through impairment of the
      balance between transforming growth factor beta and bone morphogenetic protein 7
      signaling pathways. The miR-23b/27b cluster suppresses activation of hepatic
      stellate cells through binding gremlin1 to rectify the imbalance.

PMID- 27863391
TI  - Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor
      metastasis by suppressing neuropilin 1.
AB  - Tumor metastasis is a major cause leading to the deaths of cancer patients.
      Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated
      to show therapeutic values in multiple diseases. In this study, we report that
      NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA
      suppresses NRP1 function by downregulating its expression, which leads to
      attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells.
      Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also
      impairs angiogenesis function of endothelial cells and fibronectin assembly by
      fibroblasts, both of which are critical to promote metastasis. Based on these
      comprehensive effects, NDGA effectively suppresses tumor metastasis in nude mice
      model. Our findings reveal a novel mechanism underlying the anti-metastasis
      function of NDGA and indicate the potential value of NDGA in NRP1 targeting
      therapy for selected subtypes of cancer.

PMID- 27863392
TI  - Discovery of BPR1K871, a quinazoline based, multi-kinase inhibitor for the
      treatment of AML and solid tumors: Rational design, synthesis, in vitro and in
      vivo evaluation.
AB  - The design and synthesis of a quinazoline-based, multi-kinase inhibitor for the
      treatment of acute myeloid leukemia (AML) and other malignancies is reported.
      Based on the previously reported furanopyrimidine 3, quinazoline core containing
      lead 4 was synthesized and found to impart dual FLT3/AURKA inhibition (IC50 =
      127/5 nM), as well as improved physicochemical properties. A detailed structure
      activity relationship study of the lead 4 allowed FLT3 and AURKA inhibition to be
      finely tuned, resulting in AURKA selective (5 and 7; 100-fold selective over
      FLT3), FLT3 selective (13; 30-fold selective over AURKA) and dual FLT3/AURKA
      selective (BPR1K871; IC50 = 19/22 nM) agents. BPR1K871 showed potent anti
      proliferative activities in MOLM-13 and MV4-11 AML cells (EC50 ~ 5 nM). Moreover,
      kinase profiling and cell-line profiling revealed BPR1K871 to be a potential
      multi-kinase inhibitor. Functional studies using western blot and DNA content
      analysis in MV4-11 and HCT-116 cell lines revealed FLT3 and AURKA/B target
      modulation inside the cells. In vivo efficacy in AML xenograft models (MOLM-13
      and MV4-11), as well as in solid tumor models (COLO205 and Mia-PaCa2), led to the
      selection of BPR1K871 as a preclinical development candidate for anti-cancer
      therapy. Further detailed studies could help to investigate the full potential of
      BPR1K871 as a multi-kinase inhibitor.

PMID- 27863393
TI  - A promoter polymorphism in APJ gene is significantly associated with blood
      pressure changes and hypertension risk in Chinese women.
AB  - The aim of this study was to interrogate the gender-specific association of 5
      well-defined polymorphisms in apelin/APJ system with both blood pressure changes
      and hypertension risk in a northeastern Chinese population. This is a population
      based case-control study, including 650 hypertensive patients and 645
      normotensive controls. Data were analyzed by STATA and Haplo.Stats. The genotype
      distributions of 5 study polymorphisms were in Hardy-Weinberg equilibrium in both
      genders. The rs7119375 and rs10501367 were completely linked. The genotypes (P =
      0.001) and alleles (P < 0.001) of rs7119375 differed significantly between
      patients and controls in women. Carriers of rs7119375-AA genotype had significant
      higher systolic blood pressure (SBP) than carriers of rs7119375-GG genotype in
      both patients and controls of female gender (P < 0.01). Moreover, carriers of
      rs7119375-A allele were 1.80 times more likely to develop hypertension relative
      to carriers of rs7119375-GG genotype after adjusting for age, body mass index and
      glucose (odds ratio: 1.80; 95% confidence interval: 1.03-3.16; P= 0.040). Further
      allele combination analysis supported the leading contribution of rs7119375 to
      hypertension risk. Our findings demonstrated that the mutation of promoter
      polymorphism rs7119375 in APJ gene was significantly associated with elevated SBP
      and increased hypertension risk in Chinese women.

PMID- 27863394
TI  - MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming
      growth factor beta1 to enhance epithelial-mesenchymal transition in breast
      cancer.
AB  - Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating
      cancer invasion and metastasis. However, the molecular mechanisms underlying this
      transition require further clarification. MDA-9/syntenin (SDCBP) expression is
      elevated in breast cancer patient samples as well as cultured breast cancer
      cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer
      cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more
      epithelial-like phenotype, along with changes in EMT markers, cytoskeletal
      rearrangement and decreased invasion. Conversely, over expressing MDA-9 in
      epithelial non-metastatic breast cancer cells instigated a change in morphology
      to a more mesenchymal phenotype with corresponding changes in EMT markers,
      cytoskeletal rearrangement and an increase in invasion. We also found that MDA-9
      upregulated active levels of known modulators of EMT, the small GTPases RhoA and
      Cdc42, via TGFbeta1. Reintroducing TGFbeta1 in MDA-9 silenced cells restored
      active RhoA and cdc42 levels, modulated cytoskeletal rearrangement and increased
      invasion. We further determined that MDA-9 interacts with TGFbeta1 via its PDZ1
      domain. Finally, in vivo studies demonstrated that silencing the expression of
      MDA-9 resulted in decreased lung metastasis and TGFbeta1 re-expression partially
      restored lung metastases. Our findings provide evidence for the relevance of MDA
      9 in mediating EMT in breast cancer and support the potential of MDA-9 as a
      therapeutic target against metastatic disease.

PMID- 27863395
TI  - High cord blood CCL22/CXCL10 chemokine ratios precede allergic sensitization in
      early childhood.
AB  - Atopic diseases are known to be characterized by a T helper (Th) 2-skewed
      immunity; however, there are few studies addressing the Th1/Th2 immunity at birth
      related to the development of atopic diseases in early childhood. We investigated
      186 children followed up regularly at the clinic for 4 years in a birth cohort
      study. The Th1-associated CXC chemokine ligand (CXCL)-10, CXCL11, and the Th2
      associated CC chemokine ligand (CCL)-17 and CCL22 were quantified in cord blood
      by multiplex Luminex kits. Specific immunoglobulin E antibodies against food and
      inhalant allergens were measured at 6 months as well as 1, 1.5, 2, 3, and 4 years
      of age. Cord blood CCL22 levels were positively associated with IgE sensitization
      at age 2, whereas cord blood CXCL10 levels were negatively associated with mite
      sensitization at age 3. Furthermore, a high cord blood CCL22/CXCL10 chemokine
      ratio was significantly associated with a higher risk of allergic sensitization
      at age 3 (OR, 1.02; 95% confidence interval [CI], 1.005-1.039; P = 0.012).
      However, cord blood Th1- and Th2-associated chemokines and their ratios were not
      associated with atopic diseases at different age. Our study indicates that a Th2
      skewed immunity at birth may increase risk of allergic sensitization but not of
      allergic outcomes later in life.

PMID- 27863396
TI  - P2rx4 deficiency in mice alleviates allergen-induced airway inflammation.
AB  - Compelling evidences point out a crucial role for extracellular nucleotides such
      as adenosine triphosphate (ATP) during inflammatory conditions. Once released
      into the extracellular space, ATP modulates migration, maturation and function of
      various inflammatory cells via activating of purinergic receptors of the P2Y- and
      P2X- family. P2RX4 is an ATP-guided ion channel expressed on structural cells
      such as alveolar epithelial and smooth muscle cells as well as inflammatory cells
      including macrophages, dendritic cells (DCs) and T cells. P2RX4 has been shown to
      interact with P2RX7 and promote NLRP3 inflammasome activation. Although P2RX7 has
      already been implicated in allergic asthma, the role of P2RX4 in airway
      inflammation has not been elucidated yet. Therefore, we used a selective
      pharmacological antagonist and genetic ablation to investigate the role of P2RX4
      in an ovalbumin (OVA) driven model of allergen-induced airway inflammation (AAI).
      Both, P2RX4 antagonist 5-BDBD treatment and P2rx4 deficiency resulted in an
      alleviated broncho alveolar lavage fluid eosinophilia, peribronchial
      inflammation, Th2 cytokine production and bronchial hyperresponsiveness.
      Furthermore, P2rx4-deficient bone marrow derived DCs (BMDCs) showed a reduced IL
      1beta production in response to ATP accompanied by a decreased P2rx7 expression
      and attenuated Th2 priming capacity compared to wild type (WT) BMDCs in vitro.
      Moreover, mice adoptively transferred with P2rx4-deficient BMDCs exhibit a
      diminished AAI in vivo. In conclusion our data suggests that P2RX4-signaling
      contributes to AAI pathogenesis by regulating DC mediated Th2 cell priming via
      modulating IL-1beta secretion and selective P2RX4-antagonists might be a new
      therapeutic option for allergic asthma.

PMID- 27863398
TI  - Unique epigenetic gene profiles define human breast cancers with poor prognosis.
AB  - Epigenetic enzymes are at the nexus of cellular regulatory cascades and can drive
      cancer-specific deregulation at all stages of the oncogenic process, yet little
      is known about their prognostic value in human patients. Here, we used qRT-PCR to
      profile at high resolution the expression of fifty-five epigenetic genes in over
      one hundred human breast cancer samples and patient-matched benign tissues. We
      correlated expression patterns with clinical and histological parameters and
      validated our findings in two independent large patient cohorts (TCGA and
      METABRIC). We found that human breast malignancies have unique epigenetic
      profiles and cluster into epigenetic subgroups. A subset of epigenetic genes
      defined an Epigenetic Signature as an independent predictor of patient survival
      that outperforms triple negative status and other clinical variables. Our results
      also suggest that breast cancer grade, but not stage, is driven by
      transcriptional alterations of epigenetic modifiers. Overall, this study uncovers
      the presence of epigenetic subtypes within human mammary malignancies and
      identifies tumor subgroups with specific pharmacologically targetable epigenetic
      susceptibilities not yet therapeutically exploited.

PMID- 27863397
TI  - Targeting GLI by GANT61 involves mechanisms dependent on inhibition of both
      transcription and DNA licensing.
AB  - The GLI genes are transcription factors and in cancers are oncogenes, aberrantly
      and constitutively activated. GANT61, a specific GLI inhibitor, has induced
      extensive cytotoxicity in human models of colon cancer. The FOXM1 promoter was
      determined to be a transcriptional target of GLI1. In HT29 cells, inhibition of
      GLI1 binding at the GLI consensus sequence by GANT61 led to inhibited binding of
      Pol II, the pause-release factors DSIF, NELF and p-TEFb. The formation of R-loops
      (RNA:DNA hybrids, ssDNA), were reduced by GANT61 at the FOXM1 promoter.
      Pretreatment of HT29 cells with alpha-amanitin reduced GANT61-induced gammaH2AX
      foci. Co-localization of GLI1 and BrdU foci, inhibited by GANT61, indicated GLI1
      and DNA replication to be linked. By co-immunoprecipitation and confocal
      microscopy, GLI1 co-localized with the DNA licensing factors ORC4, CDT1, and
      MCM2. Significant co-localization of GLI1 and ORC4 was inhibited by GANT61, and
      enrichment of ORC4 occurred at the GLI binding site in the FOXM1 promoter. CDT1
      was found to be a transcription target of GLI1. Overexpression of CDT1 in HT29
      and SW480 cells reduced GANT61-induced cell death, gH2AX foci, and cleavage of
      caspase-3. Data demonstrate involvement of transcription and of DNA replication
      licensing factors by non-transcriptional and transcriptional mechanisms in the
      GLI-dependent mechanism of action of GANT61.

PMID- 27863399
TI  - Different non-synonymous polymorphisms modulate the interaction of the WRN
      protein to its protein partners and its enzymatic activities.
AB  - Werner syndrome (WS) is characterized by the premature onset of several age
      associated pathologies including cancer. The protein defective in WS patients
      (WRN) is a helicase/exonuclease involved in DNA replication and repair. Here, we
      present the results of a large-scale proteome analysis that has been undertaken
      to determine protein partners of different polymorphic WRN proteins found with
      relatively high prevalence in the human population. We expressed different
      fluorescently tagged-WRN (eYFP-WRN) variants in human 293 embryonic kidney cells
      (HEK293) and used a combination of affinity-purification and mass spectrometry to
      identify different compositions of WRN-associated protein complexes. We found
      that a WRN variant containing a phenylalanine residue at position 1074 and an
      arginine at position 1367 (eYFP-WRN(F-R)) possesses more affinity for DNA-PKc,
      KU86, KU70, and PARP1 than a variant containing a leucine at position 1074 and a
      cysteine at position 1367 (eYFP-WRN(L-C)). Such results were confirmed in a WRN
      deficient background using WS fibroblasts. Interestingly, the exonuclase activity
      of WRN recovered from immunoprecipitated eYFP-WRN(L-C) variant was lower than the
      eYFP-WRN(F-R) in WS cells. Finally, HEK293 cells and WS fibroblasts
      overexpressing the eYFP-WRN(F-R) variant were more resistant to the benzene
      metabolite hydroquinone than cells expressing the eYFP-WRN(L-C) variant. These
      results indicate that the protein-protein interaction landscape of WRN is subject
      to modulation by polymorphic amino acids, a characteristic associated with
      distinctive cell survival outcome.

PMID- 27863400
TI  - Differentiated regulation of immune-response related genes between LUAD and LUSC
      subtypes of lung cancers.
AB  - Lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) are the two
      major subtypes of lung cancer, with LUSC exhibits faster progression rate than
      LUAD. To investigate the roles of immune-response related genes (IRGs) in lung
      cancer progression, we used LUAD and LUSC samples at different cancer progression
      stages, and identified that the expression profiles of IRGs could serve as a
      better classification marker for cancerous tissues of both LUAD and LUSC. We
      found that the expression changes of IRGs were different between LUAD and LUSC.
      Cell cycle promoting genes, including KIFs and proteasomes, showed faster up
      regulation in LUSC, whereas immune response promoting genes, including MHC
      molecules and chemokines, were more rapidly repressed in LUSC. Comparative
      pathway analysis revealed that members of the Toll-like receptor and T cell
      receptor signaling pathways exhibited diverged expression changes between LUAD
      and LUSC, especially at the early cancer stages. Our results revealed the
      difference of LUAD and LUSC from the immune response point of view, and provided
      new clues for the differential treatment of LUAD and LUSC.

PMID- 27863402
TI  - A fully human anti-CD47 blocking antibody with therapeutic potential for cancer.
AB  - CD47/SIRPalpha interaction serves as an immune checkpoint for macrophage-mediated
      phagocytosis. Mouse anti-CD47 blocking antibodies had demonstrated potent
      efficacy in the treatment of both leukemic and solid tumors in preclinical
      experimentations, and therefore had moved forward rapidly into clinical trials.
      However, a fully human blocking antibody, which meets clinical purpose better,
      has not been reported for CD47 up to date. In this study, we reported the
      isolation of a fully human anti-CD47 blocking antibody, ZF1, from a phage display
      library. ZF1 displayed high specificity and affinity for CD47 protein, which were
      comparable to those for humanized anti-CD47 blocking antibody B6H12. Importantly,
      ZF1 treatment could induce robust, or even stronger than B6H12, phagocytosis of
      leukemic cancer cells by macrophage in vitro, and protect BALB/c nude mice from
      cancer killing by engrafted leukemic cells (CCRF and U937) to a similar extent as
      B6H12 did. Thus, these data provide primary early pre-clinical support for the
      development of ZF1 as a fully human blocking antibody to treat human leukemia by
      targeting CD47 molecule.

PMID- 27863401
TI  - Isoliquiritigenin decreases the incidence of colitis-associated colorectal cancer
      by modulating the intestinal microbiota.
AB  - Imbalances in intestinal bacteria correlate with colitis-associated colorectal
      cancer (CAC). Traditional Chinese medicines have been used to adjust the gut
      microbiota, and isoliquiritigenin (ISL), a flavonoid extracted from licorice, has
      shown antitumor efficacy. In this study, the effects of ISL on CAC development
      and the gut microbiota were evaluated using an azoxymethane and dextran sulphate
      sodium (AOM/DSS)-induced mouse model of CAC (CACM). Histopathological analysis
      suggested that ISL reduced tumor incidence in vivo. Moreover, high-throughput
      sequencing and terminal restriction fragment length polymorphism (T-RFLP) studies
      of the bacterial 16S rRNA gene revealed that the structure of the gut microbial
      community shifted significantly following AOM/DSS treatment, and that effect was
      alleviated by treatment with high-dose ISL (150 mg/kg). Compared to the
      microbiota in the control mice (CK), the levels of Bacteroidetes decreased and
      the levels of Firmicutes increased during CAC development. ISL reversed the
      imbalance at the phylum level and altered the familial constituents of the gut
      microbiota. Specifically, the abundance of Helicobacteraceae increased after
      treatment with high-dose ISL, while the abundance of Lachnospiraceae and
      Rikenellaceae decreased. At the genus level, ISL reduced the abundance of
      opportunistic pathogens (Escherichia and Enterococcus), and increased the levels
      of probiotics, particularly butyrate-producing bacteria (Butyricicoccus,
      Clostridium, and Ruminococcus). Thus, ISL protects mice from AOM/DSS-induced CAC,
      and ISL and the gut microbiota may have synergistic anti-cancer effects.

PMID- 27863403
TI  - Enumeration and targeted analysis of KRAS, BRAF and PIK3CA mutations in CTCs
      captured by a label-free platform: Comparison to ctDNA and tissue in metastatic
      colorectal cancer.
AB  - Treatment of advanced colorectal cancer (CRC) requires multimodal therapeutic
      approaches and need for monitoring tumor plasticity. Liquid biopsy biomarkers,
      including CTCs and ctDNA, hold promise for evaluating treatment response in real
      time and guiding therapeutic modifications. From 15 patients with advanced CRC
      undergoing liver metastasectomy with curative intent, we collected 41 blood
      samples at different time points before and after surgery for CTC isolation and
      quantification using label-free Vortex technology. For mutational profiling,
      KRAS, BRAF, and PIK3CA hotspot mutations were analyzed in CTCs and ctDNA from 23
      samples, nine matched liver metastases and three primary tumor samples.
      Mutational patterns were compared. 80% of patient blood samples were positive for
      CTCs, using a healthy baseline value as threshold (0.4 CTCs/mL), and 81.4% of
      captured cells were EpCAM+ CTCs. At least one mutation was detected in 78% of our
      blood samples. Among 23 matched CTC and ctDNA samples, we found a concordance of
      78.2% for KRAS, 73.9% for BRAF and 91.3% for PIK3CA mutations. In several cases,
      CTCs exhibited a mutation that was not detected in ctDNA, and vice versa.
      Complementary assessment of both CTCs and ctDNA appears advantageous to assess
      dynamic tumor profiles.

PMID- 27863404
TI  - Kallikrein-related peptidase 6 induces chemotherapeutic resistance by attenuating
      auranofin-induced cell death through activation of autophagy in gastric cancer.
AB  - Kallikrein-related peptidase 6 (KLK6) is a biomarker of gastric cancer associated
      with poor prognosis. Mechanisms by which KLK6 could be exploited for
      chemotherapeutic use are unclear. We evaluated auranofin (AF), a compound with
      cytotoxic effects, in KLK6-deficient cells, and we investigated whether KLK6
      expression induces autophagy and acquisition of drug resistance in gastric
      cancer. Using cultured human cells and a mouse xenograft model, we investigated
      how KLK6 affects antitumor-reagent-induced cell death and autophagy. Expression
      levels of KLK6, p53, and autophagy marker LC3B were determined in gastric cancer
      tissues. We analyzed the effects of knockdown/overexpression of KLK6, LC3B, and
      p53 on AF-induced cell death in cancer cells. Increased KLK6 expression in human
      gastric cancer tissues and cells inhibited AF-induced cell motility due to
      increased autophagy and p53 levels. p53 dependent induction of KLK6 expression
      increased autophagy and drug resistance, whereas KLK6 silencing decreased the
      autophagy level and increased drug sensitivity. During AF-induced cell death,
      KLK6 and LC3B colocalized to autophagosomes, associated with p53, and were then
      trafficked to the cytosol. In the xenograft model of gastric cancer, KLK6
      expression decreased AF-induced cell death and KLK6-induced autophagy increased
      AF resistance. Taken together, the data suggest that the induction of autophagic
      processes through KLK6 expression may increase acquisition of resistance to AF.
      Our findings may contribute to a new paradigm for tumor therapeutics.

PMID- 27863405
TI  - Identification of evolutionarily conserved DNA damage response genes that alter
      sensitivity to cisplatin.
AB  - Ovarian, head and neck, and other cancers are commonly treated with cisplatin and
      other DNA damaging cytotoxic agents. Altered DNA damage response (DDR)
      contributes to resistance of these tumors to chemotherapies, some targeted
      therapies, and radiation. DDR involves multiple protein complexes and signaling
      pathways, some of which are evolutionarily ancient and involve protein orthologs
      conserved from yeast to humans. To identify new regulators of cisplatin
      resistance in human tumors, we integrated high throughput and curated datasets
      describing yeast genes that regulate sensitivity to cisplatin and/or ionizing
      radiation. Next, we clustered highly validated genes based on chemogenomic
      profiling, and then mapped orthologs of these genes in expanded genomic networks
      for multiple metazoans, including humans. This approach identified an enriched
      candidate set of genes involved in the regulation of resistance to radiation
      and/or cisplatin in humans. Direct functional assessment of selected candidate
      genes using RNA interference confirmed their activity in influencing cisplatin
      resistance, degree of gammaH2AX focus formation and ATR phosphorylation, in
      ovarian and head and neck cancer cell lines, suggesting impaired DDR signaling as
      the driving mechanism. This work enlarges the set of genes that may contribute to
      chemotherapy resistance and provides a new contextual resource for interpreting
      next generation sequencing (NGS) genomic profiling of tumors.

PMID- 27863406
TI  - STC2 promotes head and neck squamous cell carcinoma metastasis through modulating
      the PI3K/AKT/Snail signaling.
AB  - The mammalian peptide hormone stanniocalcin 2 (STC2) plays an oncogenic role in
      many human cancers. However, the exact function of STC2 in human head and neck
      squamous cell carcinoma (HNSCC) is unclear. We aimed to examine the function and
      clinical significance of STC2 in HNSCC. Using in vitro and in vivo assays, we
      show that overexpression of STC2 suppressed cell apoptosis, promoted cell
      proliferation, migration, invasion, and cell cycle arrest at the G1/S transition.
      By contrast, silencing of STC2 inhibited these activities. We further show that
      STC2 upregulated the phosphorylation of AKT and enhanced HNSCC metastasis via
      Snail-mediated increase of vimentin and decrease of E-cadherin. These responses
      were blocked by silencing of STC2/Snail expression or inhibition of pAKT
      activity. Furthermore, clinical data indicate that high STC2 expression was
      associated with high levels of pAKT and Snail in tumor samples from HNSCC
      patients with regional lymph node metastasis (P < 0.01). Thus, we conclude that
      STC2 controls HNSCC metastasis via the PI3K/AKT/Snail signaling axis and that
      targeted therapy against STC2 may be a novel strategy to effectively treat
      patients with metastatic HNSCC.

PMID- 27863407
TI  - Induction of mitochondria-mediated apoptosis and PI3K/Akt/ mTOR-mediated
      autophagy by aflatoxin B2 in hepatocytes of broilers.
AB  - Aflatoxins have been shown to induce hepatotoxicity in animal models, but the
      effects of aflatoxin B2 (AFB2) on broiler hepatocytes is unclear. This study
      aimed to investigate the effects of AFB2 on apoptosis and autophagy to provide an
      experimental basis for understanding the mechanism of aflatoxin-induced
      hepatotoxicity. One hundred-twenty Cobb500 broilers were allocated to four groups
      and exposed to 0 mg/kg, 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg of AFB2 per day for
      21 d. AFB2 exerted potent proapoptotic and proautophagic effects on hepatocytes,
      with increased numbers of apoptotic and autophagic hepatocytes.Poly ADP-ribose
      polymerase (PARP) was cleaved and caspase-3 was activated in experimental groups,
      showing that the apoptosis of hepatocytes was triggered by AFB2. Increased levels
      of the autophagy factors Beclin-1 and LC3-II/LC3-I, as well as down-regulation of
      p62, a marker of autophagic flux, provided additional evidence for AFB2-triggered
      autophagy. AFB2 induced mitochondria-mediated apoptosis via the production of
      reactive oxygen species (ROS) and promotion of the translocation of Bax and
      cytochrome c (cyt c) between mitochondria and the cytosol, triggering the
      formation of apoptosomes. AFB2 also inhibited the phosphoinositide 3
      kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway by activating
      PI3K, Akt, and mTOR and inhibiting their phosphorylation, contributing to the
      proautophagic activity of AFB2. These findings provide new insights into the
      mechanisms involved in AFB2-induced hepatotoxicity in broilers.

PMID- 27863408
TI  - An 8-gene signature for prediction of prognosis and chemoresponse in non-small
      cell lung cancer.
AB  - Identification of a potential gene signature for improved diagnosis in non-small
      cell lung cancer (NSCLC) patient is necessary. Here, we aim to establish and
      validate the prognostic efficacy of a gene set that can predict prognosis and
      benefits of adjuvant chemotherapy (ACT) in NSCLC patients from various
      ethnicities. An 8-gene signature was calculated from the gene expression of 181
      patients using univariate Cox proportional hazard regression analysis. The
      prognostic value of the signature was robustly validated in 1,477 patients from
      five microarray independent data sets and one RNA-seq data set. The 8-gene
      signature was identified as an independent predictor of patient survival in the
      presence of clinical parameters in univariate and multivariate analyses [hazard
      ratio (HR): 2.84, 95% confidence interval CI (1.74-4.65), p=3.06e-05, [HR] 2.62,
      95% CI (1.51-4.53), p=0.001], respectively. Subset analysis demonstrated that the
      8-gene signature could identify high-risk patients in stage II-III with improved
      survival from ACT [(HR) 1.47, 95% CI (1.01-2.14), p=0.044]. The 8-gene signature
      also stratified risk groups in EGFR-mutated and wild-type patients. In
      conclusion, the 8-gene signature is a strong and independent predictor that can
      significantly stratify patients into low- and high-risk groups. Our gene
      signature also has the potential to predict patients in stage II-III that are
      likely to benefit from ACT.

PMID- 27863410
TI  - Elevated expression of STIM1 is involved in lung tumorigenesis.
AB  - This study aimed to address the potential role of STIM1 (stromal interaction
      molecule 1) in lung tumorigenesis. Colony formation in soft agar assay and
      tumorigenicity in nude mice assay were conducted. Western blot,
      immunohistochemistry and quantitative real-time polymerase chain reaction were
      used to measure the STIM1 expression. The distribution of cell cycle was detected
      by flow cytometry assay. Our results showed that the expression of STIM1 mRNA was
      significantly higher in human lung tumors than that in adjacent non-neoplastic
      lung tissues. Significantly increased expression of STIM1 mRNA and protein was
      observed in 16HBE-benzo(a)pyrene (BaP) cells and in BaP-treated mice lung tissues
      compared with 16HBE-control cells and the control group, respectively. Silencing
      STIM1 inhibited the proliferation and colony formation of A549 cells in in vitro
      experiments, attenuated the growth of tumor xenografts of A549 cells in in vivo
      experiments and induced the arrest of cell cycle in the G1 phase. The markedly
      decreased expression of cyclin D1 protein was observed in A549-shRNA-STIM1 cells
      as compared to A549-shRNA-control cells. The markedly increased expression of p21
      protein was observed in A549-shRNA-STIM1 cells as compared to A549-shRNA-control
      cells. The expression levels of beta-catenin and TGIF proteins were lower in A549
      shRNA-STIM1 cells than those in A549-shRNA-control cells. In conclusion, this
      study indicated that the elevated expression of STIM1 might be involved in lung
      tumorigenesis.

PMID- 27863409
TI  - Integrating mechanisms of response and resistance against the tubulin binding
      agent Eribulin in preclinical models of osteosarcoma.
AB  - Osteosarcoma is the most frequently occurring bone cancer in children and
      adolescents. Unfortunately, treatment failures are common. Eribulin is a
      synthetic microtubule inhibitor that has demonstrated activity in preclinical
      osteosarcoma models. The effects of eribulin were evaluated in two human
      osteosarcoma cell lines as well as in eribulin-sensitive and -resistant
      osteosarcoma xenograft tumors of the Pediatric Preclinical Testing Program (PPTP)
      by characterizing cell viability, microtubule destabilization, mitotic arrest and
      mechanism of cell death. Eribulin demonstrated cytotoxic activity in vitro,
      through promotion of microtubule dynamic instability, arrest of cells in the G2/M
      phase, mitotic catastrophe and cell death. The microtubule-destabilizing protein
      stathmin-1 (STMN1) was coimmunoprecipitated with the cyclin-dependent kinase
      inhibitor p27 indicating that these cytoplasmic complexes can protect cells from
      the microtubule destabilizing effect of eribulin. Increased tumoral expression of
      P-glycoprotein (P-gp) and TUBB3 were also associated with lower drug sensitivity.
      In summary, eribulin successfully blocked cells in G2/M phase but interfered with
      mitochondria activity to inhibit proteins involved in apoptosis. Understanding
      the complex and inter-related mechanisms involved in the overall drug response to
      eribulin may help in the design of therapeutic strategies that enhance drug
      activity and improve benefits of eribulin in pediatric patients with
      osteosarcoma.

PMID- 27863411
TI  - Sesamin inhibits IL-1beta-stimulated inflammatory response in human
      osteoarthritis chondrocytes by activating Nrf2 signaling pathway.
AB  - Sesamin, a bioactive component extracted from sesame, has been reported to exert
      anti-inflammatory and anti-oxidant effects. In this study, we evaluated the anti
      inflammatory effects of sesamin on IL-1beta-stimulated human osteoarthritis
      chondrocytes and investigated the possible mechanism. Results demonstrated that
      sesamin treatment significantly inhibited PGE2 and NO production induced by IL
      1beta. Sesamin inhibited MMP1, MMP3, and MMP13 production in IL-1beta-stimulated
      chondrocytes. Sesamin also inhibited IL-1beta-induced phosphorylation of NF
      kappaB p65 and IkappaBalpha. Meanwhile, sesamin was found to up-regulate the
      expression of Nrf2 and HO-1. However, Nrf2 siRNA reversed the anti-inflammatory
      effects of sesamin. In conclusion, our results suggested that sesamin showed anti
      inflammatory effects in IL-1beta-stimulated chondrocytes by activating Nrf2
      signaling pathway.

PMID- 27863412
TI  - Associations between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and ovarian
      cancer.
AB  - Recent studies explored XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and
      ovarian cancer (OC) risk. However, the association between these two single
      nucleotide polymorphisms and OC risk remains conflicting. Thus, we conducted a
      comprehensive systematic review and meta-analysis to investigate the association.
      We searched the databases of PubMed, and Embase. Pooled odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated by using fixed-effect or random-effect
      models. 15 case-control studies published in 11 papers including 4,757 cases and
      8,431 controls were included in this meta-analysis. No associations were obtained
      between XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms and OC risk.
      Stratification analyses of Hardy-Weinberg equilibrium status indicated that
      rs3218536 polymorphism was associated with the decreased risk of OC when in
      analysis of combined HWE positive studies. In conclusion, this meta-analysis
      indicates that XRCC2 rs3218536 and ERCC2 rs13181 polymorphisms may not be
      associated with the risk of OC.

PMID- 27863413
TI  - RICTOR amplification identifies a subgroup in small cell lung cancer and predicts
      response to drugs targeting mTOR.
AB  - Small cell lung cancer (SCLC) is an aggressive cancer that represents ~15% of all
      lung cancers. Currently there are no targeted therapies to treat SCLC. Our
      genomic analysis of a metastatic SCLC cohort identified recurrent RICTOR
      amplification. Here, we examine the translational potential of this observation.
      RICTOR was the most frequently amplified gene observed (~14% patients), and co
      amplified with FGF10 and IL7R on chromosome 5p13. RICTOR copy number variation
      correlated with RICTOR protein expression in SCLC cells. In parallel, cells with
      RICTOR copy number (CN) gain showed increased sensitivity to three mTOR
      inhibitors, AZD8055, AZD2014 and INK128 in cell growth assays, with AZD2014
      demonstrating the best inhibition of downstream signaling. SCLC cells with RICTOR
      CN gain also migrated more rapidly in chemotaxis and scratch wound assays and
      were again more sensitive to mTOR inhibitors. The overall survival in SCLC
      patients with RICTOR amplification was significantly decreased (p = 0.021). Taken
      together, our results suggest that SCLC patients with RICTOR amplification may
      constitute a clinically important subgroup because of their potential response to
      mTORC1/2 inhibitors.

PMID- 27863414
TI  - Smoking increases risks of all-cause and breast cancer specific mortality in
      breast cancer individuals: a dose-response meta-analysis of prospective cohort
      studies involving 39725 breast cancer cases.
AB  - Smoking is associated with the risks of mortality from breast cancer (BC) or all
      causes in BC survivors. Two-stage dose-response meta-analysis was conducted. A
      search of PubMed and Embase was performed, and a random-effect model was used to
      yield summary hazard ratios (HRs). Eleven prospective cohort studies were
      included. The summary HR per 10 cigarettes/day, 10 pack-years, 10 years increase
      were 1.10 (95% confidence interval (CI) = 1.04-1.16), 1.09 (95% CI = 1.06-1.12),
      1.10 (95% CI = 1.06-1.14) for BC specific mortality, and 1.15 (95% CI = 1.10
      1.19), 1.15 (95% CI = 1.10-1.20), 1.17 (95% CI = 1.11-1.23) for all-cause
      mortality, respectively. The linear or non-linear associations between smoking
      and risks of mortality from BC or all causes were revealed. Subgroup analyses
      suggested a positive association between ever or former smoking and the risk of
      all-cause mortality in BC patients, especially in high doses consumption. In
      conclusion, higher smoking intensity, more cumulative amount of cigarettes
      consumption and longer time for smoking is associated with elevated risk of
      mortality from BC and all causes in BC individuals. The results regarding smoking
      cessation and "ever or former" smokers should be treated with caution due to
      limited studies.

PMID- 27863416
TI  - CRISPR-mediated multiplexed genetic manipulation.

PMID- 27863415
TI  - Induction of the mitochondria-mediated apoptosis in human esophageal cancer cells
      by DS2, a newly synthetic diterpenoid analog, is regulated by Bax and caused by
      generation of reactive oxygen species.
AB  - Ent-kaurane diterpene compounds have attracted considerable attention in recent
      years due to its antitumor, antibacterial, and antiviral activities. However, the
      clinical development of natural kaurane diterpenes, for example, oridonin for
      cancer therapy has been hampered by its relatively moderate potency, limited
      bioavailability. Herein, we report a newly synthetic analog of natural ent
      kaurane diterpene, DS2, which exhibits significantly improved activity of
      antiproliferation against various cancer cell lines relative to oridonin. DS2
      treatment triggers the mitochondria-mediated apoptosis and cell cycle arrest in
      human esophageal cancer cell lines (EC9706, EC109). Interestingly, normal human
      esophageal epithelial cells (HEECs) and normal human liver cells (HL-7702) are
      both significantly more resistant to the growth inhibition by DS2 compared with
      esophageal cancer cells. The DS2-induced apoptosis in EC9706 cells correlated
      with the drop of mitochondrial membrane potential (MMP), release of cytochrome c
      into the cytosol and activation of caspase-9 and -3. The induction of
      proapoptotic proteins p21 and Bax were also observed in DS2-treated cells. The
      DS2-induced apoptosis was significantly attenuated by knockdown of Bax proteins.
      Meanwhile, the DS2 treatment caused generation of reactive oxygen species (ROS)
      in human esophageal cancer cells, but not in HEECs, which was attenuated by
      pretreatment with ROS scavenger N-acetylcysteine (NAC). More interestingly, the
      antioxidants pretreatment completely attenuated DS2 mediated loss of the MMP and
      apoptosis, as well as Bax expression and growth inhibition. In conclusion, the
      present study reveals that the mitochondria-mediated cell death by DS2 is
      associated with Bax regulation and ROS generation, and understanding the function
      and mechanism of DS2 will help us to design better anti-cancer drugs.

PMID- 27863417
TI  - Hyponatremia normalization as an independent prognostic factor in patients with
      advanced non-small cell lung cancer treated with first-line therapy.
AB  - The aim of the study was to assess, for the first time, the prognostic role of
      hyponatremia and sodium normalization in patients receiving first-line chemo- or
      targeted therapy for advanced non-small cell lung cancer.Four hundred thirty
      three patients with advanced non small cell lung cancer were treated with first
      line chemo- or targeted therapy between 2006 and 2015 at our institutions.
      Patients were stratified in two groups, with or without hyponatremia (group A and
      B, respectively). Progression free survival (PFS) and overall survival (OS) were
      estimated using Kaplan-Meier method. A Cox regression model was carried out for
      univariate and multivariate analyses.Sixty-nine patients (16%) presented with
      hyponatremia at the start of first-line therapy. The median OS was 8.78 months in
      Group A and 15.5 months in Group B (p < 0.001), while the median PFS was 4.1
      months and 6.3 months respectively (p = 0.24). In Group A, median OS was
      significantly higher in patients who normalized their sodium levels (11.6 vs. 4.7
      months, p = 0.0435). Similarly, the median PFS was significantly higher in
      patients who normalized their sodium levels (6.7 vs. 3.3 months, p = 0.011). At
      multivariate analysis, sodium normalization was an independent prognostic factor
      for both OS and PFS.Sodium normalization during first-line therapy is an
      independent prognostic factor for OS and PFS in patients with advanced lung
      cancer treated with first-line therapies. Frequent clinical monitoring and prompt
      treatment of hyponatremia should be emphasized to optimize the outcome of these
      patients.

PMID- 27863418
TI  - Pin1 induces the ADP-induced migration of human dental pulp cells through P2Y1
      stabilization.
AB  - PIN1, which belongs to a family of prolyl isomerases, specifically binds to
      phosphorylated Ser/Thr-pro motifs to catalytically regulate the post
      phosphorylation conformation of its substrates. This study aimed to investigate
      the importance of Pin1 expression in human dental pulp cells (hDPCs) to
      understand the involvement of Pin1 in the regulation of P2Y1 and the activation
      of ADP-mediated P2Y1 signaling. This study found that the protein levels of P2Y1
      gradually decreased after the onset of cell recovery following heat stress.
      Interestedly, hDPC migration significantly decreased during the recovery period.
      An in vitro study revealed that the silencing of PIN1 by siRNA or the
      pharmacologic inhibition of its activity decreased the migration of P2Y1 and P2Y1
      expression in these cells. In addition, we found that Pin1 directly interacts
      with S252 of P2Y1 and that its binding stabilizes the P2Y1 protein to increase
      migration activity. These results strongly suggest that Pin1 mediates cell
      migration by stabilizing P2Y1 and that the Pin1/P2Y1 signaling pathways might
      serve as a novel mechanism of cell migration progression in hDPCs.

PMID- 27863419
TI  - TSC loss distorts DNA replication programme and sensitises cells to genotoxic
      stress.
AB  - Tuberous Sclerosis (TSC) is characterized by exorbitant mTORC1 signalling and
      manifests as non-malignant, apoptosis-prone neoplasia. Previous reports have
      shown that TSC-/- cells are highly susceptible to mild, innocuous doses of
      genotoxic stress, which drive TSC-/- cells into apoptotic death. It has been
      argued that this hypersensitivity to stress derives from a metabolic/energetic
      shortfall in TSC-/- cells, but how metabolic dysregulation affects the DNA damage
      response and cell cycle alterations in TSC-/- cells exposed to genotoxic stress
      is not understood. We report here the occurrence of futile checkpoint responses
      and an unusual type of replicative stress (RS) in TSC1-/- fibroblasts exposed to
      low-dose genotoxins. This RS is characterized by elevated nucleotide
      incorporation rates despite only modest origin over-firing. Strikingly, an
      increased propensity for asymmetric fork progression and profuse chromosomal
      aberrations upon mild DNA damage confirmed that TSC loss indeed proved
      detrimental to stress adaptation. We conclude that low stress tolerance of TSC-/-
      cells manifests at the level of DNA replication control, imposing strong negative
      selection on genomic instability that could in turn detain TSC-mutant tumours
      benign.

PMID- 27863420
TI  - YWHAE silencing induces cell proliferation, invasion and migration through the up
      regulation of CDC25B and MYC in gastric cancer cells: new insights about YWHAE
      role in the tumor development and metastasis process.
AB  - We previously observed reduced YWHAE (14-3-3epsilon) protein expression in a
      small set of gastric cancer samples. YWHAE may act as a negative regulator of the
      cyclin CDC25B, which is a transcriptional target of MYC oncogene. The
      understanding of YWHAE role and its targets is important for the better knowledge
      of gastric carcinogenesis. Thus, we aimed to evaluate the relationship among
      YWHAE, CDC25B, and MYC in vitro and in vivo. For this, we analyzed the YWHAE,
      CDC25B, and MYC expression in YWHA-silenced, CDC25B-silenced, and MYC-silenced
      gastric cancer cell lines, as well as in gastric cancer and non-neoplastic
      gastric samples. In gastric cancer cell lines, YWHAE was able to inhibit the cell
      proliferation, invasion and migration through the reduction of MYC and CDC25B
      expression. Conversely, MYC induced the cell proliferation, invasion and
      migration through the induction of CDC25B and the reduction of YWHAE. Most of the
      tumors presented reduced YWHAE and increased CDC25B expression, which seems to be
      important for tumor development. Increased MYC expression was a common finding in
      gastric cancer and has a role in poor prognosis. In the tumor initiation, the
      opposite role of YWHAE and CDC25B in gastric carcinogenesis seems to be
      independent of MYC expression. However, the inversely correlation between YWHAE
      and MYC expression seems to be important for gastric cancer cells invasion and
      migration. The interaction between YWHAE and MYC and the activation of the
      pathways related to this interaction play a role in the metastasis process.

PMID- 27863421
TI  - LncRNA GAS5 contributes to lymphatic metastasis in colorectal cancer.
AB  - Colorectal cancer (CRC) ranks the third most common type of cancer worldwide.
      However, the detailed molecular mechanisms underlying these processes are poorly
      understood. Recent studies have shown that lncRNAs play important roles in
      carcinogenesis and progression of CRC. The lncRNA growth arrest special 5 (GAS5),
      was previously identified to be down-regulated and functions as a tumor
      suppressor gene in many kinds of cancers. In current two-stage, case-control
      study, we systematically evaluated the potential role of lncRNA GAS5 and its
      genetic variation rs145204276 in the development and metastasis process of CRC in
      a Chinese population. We found the allele del of rs145204276 was significantly
      associated with 21% decreased risk of CRC (OR=0.79; 95% CI=0.70-0.89; P value =
      5.21*10-5). Compared with the genotype ins/ins, both the genotype ins/del
      (OR=0.78; 95% CI=0.68-0.91) and del/del (OR=0.64; 95% CI=0.49-0.84) showed
      decreased susceptibility. For both in colon and rectum cancers, the associations
      kept statistically significant (OR=O.78 and 0.80, while P value = 4.56*10-4, and
      3.80*10-3, respectively). The results also showed that the carriers of allele del
      are less likely to get lymph node metastasis (OR=0.80; 95% CI=0.68-0.95; P value
      = 0.010). Taken together, our findings provided strong evidence for the
      hypothesis that GAS5 rs145204276 were significantly associated with the
      susceptibility and progression of CRC.

PMID- 27863423
TI  - Cancer cell CCL5 mediates bone marrow independent angiogenesis in breast cancer.
AB  - It has recently been suggested that the chemokine receptor (CCR5) is required for
      bone marrow (BM) derived endothelial progenitor cell (EPC) mediated angiogenesis.
      Here we show that suppression of either cancer cell produced CCL5, or host CCR5
      leads to distinctive vascular and tumor growth defects in breast cancer.
      Surprisingly, CCR5 restoration in the BM alone was not sufficient to rescue the
      wild type phenotype, suggesting that impaired tumor growth associated with
      inhibiting CCL5/CCR5 is not due to defects in EPC biology. Instead, to promote
      angiogenesis cancer cell CCL5 may signal directly to endothelium in the tumor
      stroma. In support of this hypothesis, we have also shown: (i) that endothelial
      cell CCR5 levels increases in response to tumor-conditioned media; (ii) that the
      amount of CCR5+ tumor vasculature correlates with invasive grade; and (iii) that
      inhibition of CCL5/CCR5 signaling impairs endothelial cell migration, associated
      with a decrease in activation of mTOR/AKT pathway members. Finally, we show that
      treatment with CCR5 antagonist results in less vasculature, impaired tumor
      growth, reduced metastases and improved survival. Taken as a whole, this work
      demonstrates that directly inhibiting CCR5 expressing vasculature constitutes a
      novel strategy for inhibiting angiogenesis and blocking metastatic progression in
      breast cancer.

PMID- 27863422
TI  - In silico and in vitro drug screening identifies new therapeutic approaches for
      Ewing sarcoma.
AB  - The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less
      than 30% of patients with metastatic or recurrent disease survive despite
      aggressive combinations of chemotherapy, radiation and surgery. To identify new
      therapeutic options, we employed a multi-pronged approach using in silico
      predictions of drug activity via an integrated bioinformatics approach in
      parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and
      forty-six drugs were identified, respectively, to have anti-proliferative effects
      for EWS, including several classes of drugs in both screening approaches. Among
      these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14
      various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase
      inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer
      activities in silico and were confirmed active across a panel of genetically
      diverse EWS cells. When given in combination, the survival rate in vivo was
      superior compared to auranofin or ganetespib alone. Importantly, extensive
      formulations, dose tolerance, and pharmacokinetics studies demonstrated that
      auranofin requires alternative delivery routes to achieve therapeutically
      effective levels of the gold compound. These combined screening approaches
      provide a rapid means to identify new treatment options for patients with a rare
      and often-fatal disease.

PMID- 27863424
TI  - Novel metastatic models of esophageal adenocarcinoma derived from FLO-1 cells
      highlight the importance of E-cadherin in cancer metastasis.
AB  - There is currently a paucity of preclinical models available to study the
      metastatic process in esophageal cancer. Here we report FLO-1, and its isogenic
      derivative FLO-1LM, as two spontaneously metastatic cell line models of human
      esophageal adenocarcinoma. We show that FLO-1 has undergone epithelial
      mesenchymal transition and metastasizes following subcutaneous injection in mice.
      FLO-1LM, derived from a FLO-1 liver metastasis, has markedly enhanced
      proliferative, clonogenic, anti-apoptotic, invasive, immune-tolerant and
      metastatic potential. Genome-wide RNAseq profiling revealed a significant
      enrichment of metastasis-related pathways in FLO-1LM cells. Moreover, CDH1, which
      encodes the adhesion molecule E-cadherin, was the most significantly
      downregulated gene in FLO-1LM compared to FLO-1. Consistent with this, repression
      of E-cadherin expression in FLO-1 cells resulted in increased metastatic
      activity. Importantly, reduced E-cadherin expression is commonly reported in
      esophageal adenocarcinoma and independently predicts poor patient survival.
      Collectively, these findings highlight the biological importance of E-cadherin
      activity in the pathogenesis of metastatic esophageal adenocarcinoma and validate
      the utility of FLO-1 parental and FLO-1LM cells as preclinical models of
      metastasis in this disease.

PMID- 27863425
TI  - Identification of an HSP90 modulated multi-step process for ERBB2 degradation in
      breast cancer cells.
AB  - The receptor tyrosine kinase ERBB2 interacts with HSP90 and is overexpressed in
      aggressive breast cancers. Therapeutic HSP90 inhibitors, i.e. Geldanamycin (GA),
      target ERBB2 to degradation. We have previously shown that HSP90 is responsible
      for the missorting of recycling ERBB2 to degradation compartments. In this study,
      we used biochemical, immunofluorescence and electron microscopy techniques to
      demonstrate that in SKBR3 human breast cancer cells, GA strongly induces
      polyubiquitination and internalization of the full-length p185-ERBB2, and
      promotes its cleavage, with the formation of a p116-ERBB2 form in EEA1-positive
      endosomes (EE). p116-ERBB2 corresponds to a non-ubiquitinated, signaling
      impaired, membrane-bound fragment, which is readily sorted to lysosomes and
      degraded. To define the sequence of events leading to p116-ERBB2 degradation, we
      first blocked the EE maturation/trafficking to late endosomes/lysosomes with
      wortmannin, and found an increase in GA-dependent formation of p116-ERBB2; we
      then inhibited the proteasome activity with MG-132 or lactacystin, and observed
      an efficient block of p185-ERBB2 cleavage, and its accumulation in EE, suggesting
      that p185-ERBB2 polyubiquitination is necessary for proteasome-dependent p116
      ERBB2 generation occurring in EE. As polyubiquitination has also been implicated
      in autophagy-mediated degradation of ERBB2 under different experimental
      conditions, we exploited this possibility and demonstrate that GA strongly
      inhibits early autophagy, and reduces the levels of the autophagy markers atg5-12
      and LC3-II, irrespective of GA-induced ERBB2 polyubiquitination, ruling out a GA
      dependent autophagic degradation of ERBB2. In conclusion, we propose that HSP90
      inhibition fosters ERBB2 polyubiquitination and proteasome-dependent generation
      of a non-ubiquitinated and inactive p116-ERBB2 form in EE, which is trafficked
      from altered EE to lysosomes.

PMID- 27863426
TI  - Quantification of tumor-derived cell free DNA(cfDNA) by digital PCR (DigPCR) in
      cerebrospinal fluid of patients with BRAFV600 mutated malignancies.
AB  - Tumor-derived cell free DNA (cfDNA) can be detected in plasma. We hypothesized
      that mutated BRAF V600 cfDNA could be quantified in the cerebrospinal fluid (CSF)
      of patients with central nervous system (CNS) metastases. We collected CSF from
      patients with BRAF V600E or K-mutated melanoma (N=8) or BRAF V600E mutated
      Erdheim-Chester Disease (ECD) (N=3) with suspected central nervous system (CNS)
      involvement on the basis of neurological symptoms (10/11), MRI imaging (8/11), or
      both. Tumor-derived cfDNA was quantified by digital PCR in the CSF of 6/11
      patients (range from 0.15-10.56 copies/MUL). Conventional cytology was negative
      in all patients except in the two patients with markedly elevated levels of tumor
      derived cfDNA. In 2 patients with serial measurements, CSF tumor-derived cfDNA
      levels reflected response to treatment or progressive disease. CSF tumor-derived
      cfDNA has the potential to serve as a diagnostic tool that complements MRI and
      may be more sensitive than conventional cytology.

PMID- 27863427
TI  - Sorafenib pretreatment enhances radiotherapy through targeting MEK/ERK/NF-kappaB
      pathway in human hepatocellular carcinoma-bearing mouse model.
AB  - Patients with unresectable hepatocellular carcinoma (HCC) usually have poor
      prognosis because current monotherapy including surgery, chemotherapy and
      radiotherapy (RT) are not effective. Combination therapy may be effective to
      overcome this clinical problem. Here, we proposed the combination of sorafenib
      and RT, which have been applied in HCC treatment, could improve the treatment
      outcome of HCC. Our previous study showed that sorafenib could suppress the
      expression of NF-kappaB which is related to the chemo- and radio-resistance.
      Nevertheless, the expression of NF-kappaB is oscillatory and is affected by the
      treatments. Thus, understanding the oscillation of NF-kappaB expression would be
      beneficial for determining the optimal treatment schedule in combination therapy.
      Here established Huh7/NF-kappaB-tk-luc2/rfp cell line, in which NF-kappaB
      indicates a NF-kappaB promoter, was utilized to noninvasively monitor the
      expression of NF-kappaB overtime in vitro and in vivo. The results show that
      pretreatment of sorafenib with RT suppresses the expressions of NF-kappaB and its
      downstream proteins induced by radiation through downregulation of phosphorylated
      extracellular signal-regulated kinase (pERK) most significantly compared with
      other treatment schedules. The results were further verified with Western
      blotting, EMSA, and NF-kappaB molecular imaging. These findings suggest that
      pretreatment of sorafenib with RT may be the ideal treatment schedule for the
      treatment of HCC.

PMID- 27863428
TI  - Impact of diabetes-related gene polymorphisms on the clinical characteristics of
      type 2 diabetes Chinese Han population.
AB  - We investigated the correlation between type 2 diabetes (T2D)-related genes and
      the clinical characteristics of T2D in the Chinese Han population. Our study
      included 319 patients and 387 controls. Age, gender, clinical features,
      medications intake and biochemical blood profiles were analyzed. Genotyping was
      performed on a total of 18 single nucleotide polymorphisms previously reported to
      be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22
      rs4838605 is associated with T2D risk. Upon analyzing the subjects' clinical
      characteristics, we found that for rs2811893, the TT genotype correlated with
      high creatinine levels, while the AA genotype of rs17045754 and the TT genotype
      of rs4838605 correlated with elevated triglyceride levels. In addition, the AA
      genotype of rs17376456 and the TT genotype of rs6214 (p = 0.006) correlated with
      elevated hemoglobin A1c levels. Lastly, those carrying the TT genotype of
      rs7772697 and the CA genotype of rs3918227 exhibited higher mean body mass index
      and Cystatin C than controls. Our results showing that the ARHGAP22 gene is
      associated with an increased risk of T2D, and that seven SNPs in MYSM1, PLXDC2,
      ARHGAP22 and HS6ST3 promote T2D progression and could help predict the clinical
      course of T2D in patients at risk.

PMID- 27863429
TI  - Epigenetically upregulated WIPF1 plays a major role in BRAF V600E-promoted
      papillary thyroid cancer aggressiveness.
AB  - How the BRAF V600E mutation promotes the pathogenesis and aggressiveness of
      papillary thyroid cancer (PTC) is not completely understood. Here we explored a
      novel mechanism involving WASP interacting protein family member 1 (WIPF1). In
      PTC tumors, compared with the wild-type BRAF, BRAF V600E was associated with over
      expression and hypomethylation of the WIPF1 gene. In thyroid cancer cell lines
      with wild-type BRAF, WIPF1 expression was robustly upregulated upon introduced
      expression of BRAF V600E (P=0.03) whereas the opposite was seen upon BRAF
      knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF
      V600E. Methylation of a functionally critical region of the WIPF1 promoter was
      decreased by expressing BRAF V600E in cells harboring the wild-type BRAF and
      increased by BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in
      cells harboring BRAF V600E mutation. Under-expression and hypermethylation of
      WIPF1 induced by stable BRAF knockdown was reversed by DNA demethylating agent 5'
      azadeoxycytidine. Knockdown of WIPF1 robustly inhibited anchorage-independent
      colony formation, migration, and invasion of thyroid cancer cells and suppressed
      xenograft thyroid cancer tumor growth and vascular invasion, mimicking the
      effects of BRAF knockdown. In human PTC tumors, WIPF1 expression was associated
      with extrathyroidal invasion (P=0.01) and lymph node metastasis (P=2.64E-05). In
      summary, BRAF V600E-activated MAP kinase pathway causes hypomethylation and
      overexpression of WIPF1; WIPF1 then functions like an oncoprotein to robustly
      promote aggressive cellular and tumor behaviors of PTC. This represents a novel
      mechanism in BRAF V600E-promoted PTC aggressiveness and identifies WIPF1 as a
      novel therapeutic target for thyroid cancer.

PMID- 27863430
TI  - Diisononyl phthalate aggravates allergic dermatitis by activation of NF-kB.
AB  - Several epidemiological studies have suggested a possible link between exposure
      to Diisononyl phthalate (DINP) and the development of allergies. These findings
      remain controversial since there is insufficient scientific evidence to assess
      the ability of DINP to influence allergic immune responses. In addition, the
      mechanisms behind DINP-caused allergic diseases have not been fully elucidated.
      In this study, Balb/c mice were orally exposed to DINP for 3 weeks and were then
      sensitized with fluorescein isothiocyanate (FITC). We showed that oral exposure
      to DINP could aggravate allergic-dermatitis-like lesions, indicated by an
      increase in the number of mast cells, and in increased skin edema in FITC-induced
      contact hypersensitivity. This deterioration was concomitant with increased total
      serum immunoglobulin-E and Th2 cytokines. We determined the oxidative damage and
      the activation of nuclear factor-kb (NF-kB). The data demonstrated that DINP
      could promote oxidative damage and the activation of NF-kB in the skin. The
      expression of thymic stromal lymphopoietin and the activation of signal
      transducer and activator of transcriptions 3, 5 and 6 were enhanced concomitant
      with exacerbated allergic dermatitis effects and the activation of NF-kB induced
      by DINP. These effects were alleviated by pyrollidine dithiocarbamate, an
      inhibitor of NF-kB. The results suggest that oral exposure to DINP aggravated
      allergic contact dermatitis, which was positively regulated via NF-kB.

PMID- 27863431
TI  - Synergistic antitumor activity of the combination of salubrinal and rapamycin
      against human cholangiocarcinoma cells.
AB  - Less is known about the roles of eukaryotic initiation factor alpha (eIF2alpha)
      in cholangiocarcinoma (CCA). Here, we report that eIF2alpha inhibitor salubrinal
      inhibits the proliferation of human CCA cells. Clinical application of mammalian
      target of rapamycin (mTOR) inhibitors only has moderate antitumor efficacy.
      Therefore, combination approaches may be required for effective clinical use of
      mTOR inhibitors. Here, we investigated the efficacy of the combination of
      salubrinal and rapamycin in the treatment of CCA. Our data demonstrate a
      synergistic antitumor effect of the combination of salubrinal and rapamycin
      against CCA cells. Rapamycin significantly inhibits the proliferation of CCA
      cells. However, rapamycin initiates a negative feedback activation of Akt.
      Inhibition of Akt by salubrinal potentiates the efficacy of rapamycin both in
      vitro and in vivo. Additionally, rapamycin treatment results in the up-regulation
      of Bcl-xL in a xenograft mouse model. It is notable that salubrinal inhibits
      rapamycin-induced Bcl-xL up-regulation in vivo. Taken together, our data suggest
      that salubrinal and rapamycin combination might be a new and effective strategy
      for the treatment of CCA.

PMID- 27863432
TI  - E-cadherin downregulation sensitizes PTEN-mutant tumors to PI3Kbeta silencing.
AB  - Alterations in phosphatidylinositol 3-kinase (PI3K) and in PTEN (phosphatase and
      tensin homolog), the negative regulator of the PI3K pathway, are found in nearly
      half of human tumors. As PI3Kbeta, the main isoform activated in PTEN-mutant
      tumors, has kinase-dependent and -independent activities, we compared the effects
      of depleting vs. drug-inhibiting PI3Kbeta kinase activity in a collection of
      diverse tumor types and in a set of bladder carcinoma cell lines grown as
      xenografts in mice. PI3Kbeta depletion (by intratumor injection of PIK3CB siRNA)
      induced apoptosis and triggered regression of PTEN-mutant tumors more efficiently
      than PI3Kbeta inhibition. A small proportion of these tumors was resistant to
      PI3Kbeta downregulation; we analyzed what determined resistance in these cases.
      Using add-back experiments, we show that both PTEN mutation and low E-cadherin
      expression are necessary for PI3Kbeta dependence. In bladder carcinoma, loss of E
      cadherin expression coincides with N-cadherin upregulation. We found that
      PI3Kbeta associated with N-cadherin and that PIK3CB depletion selectively
      disrupted N-cadherin cell adhesions in PTEN-mutant bladder carcinoma. These
      results support the use of PIK3CB interfering RNA as a therapeutic approach for
      high-risk bladder cancers that show E-cadherin loss and express mutant PTEN.

PMID- 27863433
TI  - Assessment of differentially expressed plasma microRNAs in nonsyndromic cleft
      palate and nonsyndromic cleft lip with cleft palate.
AB  - Plasma microRNAs (miRNAs) have recently emerged as a new class of regulatory
      molecules that influence many biological functions. However, the expression
      profile of plasma microRNAs in nonsyndromic cleft palate (NSCP) or nonsyndromic
      cleft lip with cleft palate (NSCLP) remains poorly investigated. In this study,
      we used Agilent human miRNA microarray chips to monitor miRNA levels in three
      NSCP plasma samples (mixed as the CP group), three NSCLP plasma samples (mixed as
      the CLP group) and three normal plasma samples (mixed as the Control group). Six
      selected plasma miRNAs were validated in samples from an additional 16 CP, 33 CLP
      and 8 healthy children using qRT-PCR. Using Venn diagrams, distinct and
      overlapping dysregulated miRNAs were identified. Their respective target genes
      were further assessed using gene ontology and pathway analysis. The results show
      that distinct or overlapping biological processes and signalling pathways were
      involved in CP and CLP. Our study showed that the common key gene targets
      reflected functional relationships to the Notch, Wnt, phosphatidylinositol and
      Hedgehog signalling pathways. Further studies should examine the mechanism of the
      potential target genes, which may provide new avenues for future clinical
      prevention and therapy.

PMID- 27863434
TI  - A microRNA biomarker panel for the non-invasive detection of bladder cancer.
AB  - The development of accurate, non-invasive urinary assays for bladder cancer would
      greatly facilitate the detection and management of a disease that has a high rate
      of recurrence and progression. In this study, we employed a discovery and
      validation strategy to identify microRNA signatures that can perform as a non
      invasive bladder cancer diagnostic assay. Expression profiling of 754 human
      microRNAs (TaqMan low density arrays) was performed on naturally voided urine
      samples from a cohort of 85 subjects of known bladder disease status (27 with
      active BCa). A panel of 46 microRNAs significantly associated with bladder cancer
      were subsequently monitored in an independent cohort of 121 subjects (61 with
      active BCa) using quantitative real-time PCR (RT-PCR). Multivariable modeling
      identified a 25-target diagnostic signature that predicted the presence of BCa
      with an estimated sensitivity of 87% at a specificity of 100% (AUC 0.982). With
      additional validation, the monitoring of a urinary microRNA biomarker panel could
      facilitate the non-invasive evaluation of patients under investigation for BCa.

PMID- 27863435
TI  - Myb expression is critical for myeloid leukemia development induced by Setbp1
      activation.
AB  - SETBP1 missense mutations have been frequently identified in multiple myeloid
      neoplasms; however, their oncogenic potential remains unclear. Here we show that
      expression of Setbp1 mutants carrying two such mutations in mouse bone marrow
      progenitors efficiently induced development of acute myeloid leukemias (AMLs) in
      irradiated recipient mice with significantly shorter latencies and greater
      penetrance than expression of wild-type Setbp1, suggesting that these mutations
      are highly oncogenic. The increased oncogenicity of Setbp1 missense mutants could
      be due in part to their capability to drive significantly higher target gene
      transcription. We further identify Myb as a critical mediator of Setbp1-induced
      self-renewal as its knockdown caused efficient differentiation of myeloid
      progenitors immortalized by wild-type Setbp1 and Setbp1 missense mutants.
      Interestingly, Myb is also a direct transcriptional target of Setbp1 and Setbp1
      missense mutants as they directly bind to the Myb locus in immortalized cells and
      dramatically activate a critical enhancer/promoter region of Myb in luciferase
      reporter assays. Furthermore, Myb knockdown in Setbp1 and Setbp1 missense
      mutations-induced AML cells also efficiently induced their differentiation in
      culture and significantly prolonged the survival of their secondary recipient
      mice, suggesting that targeting MYB pathway could be a promising strategy for
      treating human myeloid neoplasms with SETBP1 activation.

PMID- 27863436
TI  - Chemotherapy plus dendritic cells co-cultured with cytokine-induced killer cells
      versus chemotherapy alone to treat advanced non-small-cell lung cancer: A meta
      analysis.
AB  - This study was aimed to investigate the efficacy and safety of the combination
      treatment of dendritic cells co-cultured with cytokine-induced killer cells and
      chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC).
      Literatures were searched from the Cochrane Library Central, PubMed, Web of
      Science and EMBASE. The primary endpoint of interest was overall survival (OS),
      and secondary endpoints were disease control rate (DCR) and progression free
      survival (PFS). Finally 7 trials published between January 2005 and March 2016
      met inclusion criteria and totally 610 patients were enrolled. The combination
      group showed advance in DCR (RR = 1.31, 95% CI = 1.13-1.52, p = 0.0004), 1-year
      OS (RR = 1.18, 95% CI = 1.05-1.33, p = 0.007), and 2-year OS (RR = 1.37, 95% CI =
      1.10-1.70, p = 0.005), with statistical significance. The proportions of CD3+ T
      cells (p = 0.002), NK cells (p = 0.02) and NKT cells (p = 0.001) were
      significantly higher in the peripheral blood of combination group, compared with
      those of the control group. Moreover, adverse reactions were obviously decreased
      in the combination group. However, no significant difference was identified in
      ORR and PFS between two groups (p > 0.05). In conclusion, the combination therapy
      was safe and applicable for patients with advanced NSCLC.

PMID- 27863437
TI  - Association of multiple genetic variants with breast cancer susceptibility in the
      Han Chinese population.
AB  - We selected 13 tag single nucleotide polymorphisms (tSNPs) to investigate whether
      they were associated with breast cancer risk in the Chinese Han population. Upon
      statistical analyses of clinical data from 551 patients and 577 controls, we
      found that six of the 13 SNPs were associated with breast cancer; namely,
      rs4973768(Odds ratio (OR) = 1.30, 95% confidence interval (CI) =1.01-1.67),
      rs981782(OR =1.30, 95% CI=1.01-1.66), rs1432679(OR =0.84, 95% CI=0.70-0.99),
      rs10759243(OR=1.30, 95%CI=1.09-1.55), rs10822013(OR =1.18, 95% CI=1.00-1.39) and
      rs704010(OR =1.63, 95% CI=1.04-2.56). When stratified based on breast cancer
      subtype, our analyses revealed that three SNPs (rs981782, rs10759243 and
      rs704010) correlated with ER+ breast cancer, while another three (rs4973768,
      rs1432679 and rs10822013) correlated with ER- breast cancer. We obtained similar
      results while investigating the correlation of SNPs with PR status or clinical
      stage. Our results suggest that associations identified between SNPs and breast
      cancer through genome-wide association studies (GWAS) may not always be
      generalizable across races.

PMID- 27863438
TI  - Immunohistochemical staining of ERG and SOX9 as potential biomarkers of docetaxel
      response in patients with metastatic castration-resistant prostate cancer.
AB  - We aimed to evaluate ERG and SOX9 as potential biomarkers of docetaxel response
      in metastatic castration-resistant prostate cancer (mCRPC) patients. Seventy-one
      mCRPC patients were evaluated. Tissue microarrays were constructed and
      immunohistochemistry was performed. Treatment response was assessed by prostate
      specific antigen (PSA) response rate, PSA progression-free survival (PSA-PFS),
      clinical/radiologic PFS (C/R-PFS) and overall survival (OS). ERG and SOX9 were
      found in 13 (18.3%) and 62 (87.3%) patients, respectively. ERG-positive had lower
      PSA response rates than negative (15.4% vs 62.1%, p = 0.004), and SOX9 showed a
      same trend (46.8% vs 100.0%, p = 0.003). ERG positivity correlated with a lower
      PSA-PFS (3.2 mos vs 7.4 mos, p < 0.001), C/R-PFS (3.8 mos vs 9.0 mos, p < 0.001)
      and OS (10.8 mos vs 21.4 mos, p < 0.001). SOX9 positivity also showed a lower PSA
      PFS, C/R-PFS and OS (p =0.006, p =0.012 and p =0.023, respectively). On
      multivariate analysis, ERG positivity was a significant risk factor for a lower
      PSA-PFS, C/R-PFS and OS (p < 0.001, p < 0.001 and p =0.001, respectively). SOX9
      expression was also a risk factor for a lower PSA-PFS, C/R-PFS and OS (p = 0.018,
      p = 0.025 and p =0.047, respectively). These findings indicate that ERG and SOX9
      is potential biomarkers for prediction to docetaxel treatment in mCRPC patients.

PMID- 27863439
TI  - Re-purposing of curcumin as an anti-metastatic agent for the treatment of
      epithelial ovarian cancer: in vitro model using cancer stem cell enriched ovarian
      cancer spheroids.
AB  - Malignant epithelial ovarian cancer (EOC) spheroids high frequently are detected
      in the malignant ascites of the patients with the extensive peritoneal metastasis
      of ovarian cancer, which represent a significant obstacle to efficacious
      treatment. Clinical data also suggested that EOC spheroids play a putative role
      in the development of chemoresistance. Since standard surgery and conventional
      chemotherapy is the only available treatment, there is an urgent need to identify
      a more effective therapeutic strategy. Recent studies demonstrated that curcumin
      exerts an anticancer effect in a variety of human cancers including ovarian
      cancer. This study evaluates anti-peritoneal metastasis and chemoresistance of
      curcumin related to the EOC spheroids. In this study, we confirm that the high
      invasive EOC cells forming the spheroids express a high level of a cancer stem
      cell (CSC) marker, aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which was
      significantly down-regulated by curcumin treatment. Curcumin treatment markedly
      enhances the sensitivity of EOC spheroids to cisplatin in a dose-dependent
      manner. Our experiments provided evidence that curcumin could abolish the sphere
      forming capacity of EOC cells in a dose-dependent manner. Moreover, curcumin
      substantially suppressed the growth of the pre-existed EOC spheroids, inhibited
      the adhesion of EOC spheroids to ECM as well as the invasion of EOC spheroids to
      the mesothelial monolayers. We propose to re-purpose curcumin as anti-metastatic
      and chemoresistant agent for EOC management in combination with conventional
      regimen. Further preclinical studies are necessary to validate the anti-cancer
      effect of curcumin in patients with EOC.

PMID- 27863440
TI  - Patient-derived glioblastoma stem cells respond differentially to targeted
      therapies.
AB  - The dismal prognosis of glioblastoma is, at least in part, attributable to the
      difficulty in eradicating glioblastoma stem cells (GSCs). However, whether this
      difficulty is caused by the differential responses of GSCs to drugs remains to be
      determined. To address this, we isolated and characterized ten GSC lines from
      established cell lines, xenografts, or patient specimens. Six lines formed
      spheres in a regular culture condition, whereas the remaining four lines grew as
      monolayer. These adherent lines formed spheres only in plates coated with poly-2
      hydroxyethyl methacrylate. The self-renewal capabilities of GSCs varied, with the
      cell density needed for sphere formation ranging from 4 to 23.8 cells/well.
      Moreover, a single non-adherent GSC either remained quiescent or divided into two
      cells in four-seven days. The stem cell identity of GSCs was further verified by
      the expression of nestin or glial fibrillary acidic protein. Of the two GSC lines
      that were injected in immunodeficient mice, only one line formed a tumor in two
      months. The protein levels of NOTCH1 and platelet derived growth factor receptor
      alpha positively correlated with the responsiveness of GSCs to gamma-secretase
      inhibitor IX or imatinib, two compounds that inhibit these two proteins,
      respectively. Furthermore, a combination of temozolomide and a connexin 43
      inhibitor robustly inhibited the growth of GSCs. Collectively, our results
      demonstrate that patient-derived GSCs exhibit different growth rates in culture,
      possess differential capabilities to form a tumor, and have varied responses to
      targeted therapies. Our findings underscore the importance of patient-derived
      GSCs in glioblastoma research and therapeutic development.

PMID- 27863442
TI  - Loss of organic anion transporting polypeptide 1B3 function causes marked delay
      in indocyanine green clearance without any clinical symptoms.

PMID- 27863441
TI  - Sulforaphane inhibits proliferation and invasive activity of everolimus-resistant
      kidney cancer cells in vitro.
AB  - Although the mechanistic target of rapamycin (mTOR) inhibitor, everolimus, has
      improved the outcome of patients with renal cell carcinoma (RCC), improvement is
      temporary due to the development of drug resistance. Since many patients
      encountering resistance turn to alternative/complementary treatment options, an
      investigation was initiated to evaluate whether the natural compound,
      sulforaphane (SFN), influences growth and invasive activity of everolimus
      resistant (RCCres) compared to everolimus-sensitive (RCCpar) RCC cell lines in
      vitro. RCC cells were exposed to different concentrations of SFN and cell growth,
      cell proliferation, apoptosis, cell cycle, cell cycle regulating proteins, the
      mTOR-akt signaling axis, adhesion to human vascular endothelium and immobilized
      collagen, chemotactic activity, and influence on surface integrin receptor
      expression were investigated. SFN caused a significant reduction in both RCCres
      and RCCpar cell growth and proliferation, which correlated with an elevation in
      G2/M- and S-phase cells. SFN induced a marked decrease in the cell cycle
      activating proteins cdk1 and cyclin B and siRNA knock-down of cdk1 and cyclin B
      resulted in significantly diminished RCC cell growth. SFN also modulated adhesion
      and chemotaxis, which was associated with reduced expression of the integrin
      subtypes alpha5, alpha6, and beta4. Distinct differences were seen in RCCres
      adhesion and chemotaxis (diminished by SFN) and RCCpar adhesion (enhanced by SFN)
      and chemotaxis (not influenced by SFN). Functional blocking of integrin subtypes
      demonstrated divergent action on RCC binding and invasion, depending on RCC cell
      sensitivity to everolimus. Therefore, SFN administration could hold potential for
      treating RCC patients with established resistance towards everolimus.

PMID- 27863443
TI  - Gait assessment with solesound instrumented footwear in spinal muscular atrophy.
AB  - INTRODUCTION: Gait impairment is common in spinal muscular atrophy (SMA) and is
      described using clinical assessments and instrumented walkways. Continuous over
      ground walking has not been studied. METHODS: Nine SMA participants completed the
      6-minute walk test (6MWT) and 10-meter walk/run wearing instrumented footwear
      (SoleSound). Data were simultaneously collected using a reference system
      (GAITRite). The root-mean-square error (RMSE) indicated criterion validity. The
      decrease in walking speed represented fatigue. Foot loading patterns were
      evaluated using force sensors. RESULTS: The RMSE for stride time, length, and
      velocity ranged from 1.3% to 1.7%. Fatigue was 11.6 +/- 9.1%, which corresponded
      to an average deceleration of 0.37 +/- 0.28 mm/s2 . Participants spent most of
      their stance without heel contact. Forefoot contact occurred early in the gait
      cycle. CONCLUSIONS: These results suggest that footwear-based devices are an
      alternative to specialized equipment for gait assessment. Better understanding of
      gait disturbances should inform ongoing treatment efforts and provide a more
      sensitive outcome measure. Muscle Nerve 56: 230-236, 2017.

PMID- 27863445
TI  - Dissociable profiles of generalization/discrimination in the human hippocampus
      during associative retrieval.
AB  - When encountering stimuli that vary slightly from previous experiences, neural
      signals within the CA3 and dentate gyrus (CA3 DG) hippocampal subfields are
      thought to facilitate mnemonic discrimination, whereas CA1 may be less sensitive
      to minor stimulus changes, allowing for generalization across similar events.
      Studies have also posited a critical role for CA1 in the comparison of events to
      memory-derived expectations, but the degree to which these processes are impacted
      by explicit retrieval demands is yet unclear. To evaluate extant accounts of
      hippocampal subfield function, we acquired high-resolution fMRI data as
      participants performed a task in which famous names were used to cue the
      retrieval of previously paired images. Although both left CA3 DG and CA1 showed
      match enhancement effects, responding more to original paired images (targets)
      than to never-before-seen images (novels), the sensitivity of these subfields to
      stimulus changes and task demands diverged. CA3 DG showed a goal-independent, yet
      highly specific, preference for previously encountered stimuli, responding
      equally strongly to targets and mispaired associates, while showing equally weak
      responses to close lures and novels. In contrast, recognition signals in CA1 were
      goal-dependent (i.e., not evoked by mispaired associates), yet accommodating of
      subtle stimulus differences, such that close lures evoked comparable activity as
      targets. (c) 2016 Wiley Periodicals, Inc.

PMID- 27863444
TI  - AV-1451 tau and beta-amyloid positron emission tomography imaging in dementia
      with Lewy bodies.
AB  - OBJECTIVE: Patients with probable dementia with Lewy bodies (DLB) often have
      Alzheimer's disease (AD)-related pathology. Our objective was to determine the
      pattern of positron emission tomography (PET) tau tracer AV-1451 uptake in
      patients with probable DLB, compared to AD, and its relationship to beta-amyloid
      deposition on PET. METHODS: Consecutive patients with clinically probable DLB (n
      = 19) from the Mayo Clinic Alzheimer's Disease Research Center underwent magnetic
      resonance imaging, AV-1451, and Pittsburgh compound-B (PiB) PET examinations. Age
      and sex-matched groups of AD dementia (n = 19) patients and clinically normal
      controls (n = 95) from an epidemiological cohort served as a comparison groups.
      Atlas- and voxel-based analyses were performed. RESULTS: The AD dementia group
      had significantly higher AV-1451 uptake than the probable DLB group, and medial
      temporal uptake completely distinguished AD dementia from probable DLB. Patients
      with probable DLB had greater AV-1451 uptake in the posterior temporoparietal and
      occipital cortex compared to clinically normal controls, and in probable DLB, the
      uptake in these regions correlated with global cortical PiB uptake (Spearman rho
      = 0.63; p = 0.006). INTERPRETATION: Medial temporal lobe AV-1451 uptake
      distinguishes AD dementia from probable DLB, which may be useful for differential
      diagnosis. Elevated posterior temporoparietal and occipital AV-1451 uptake in
      probable DLB and its association with global cortical PiB uptake suggest an
      atypical pattern of tau deposition in DLB. ANN NEUROL 2017;81:58-67.

PMID- 27863446
TI  - Glutathione transferase P1-1 as an arsenic drug-sequestering enzyme.
AB  - Arsenic-based compounds are paradoxically both poisons and drugs. Glutathione
      transferase (GSTP1-1) is a major factor in resistance to such drugs. Here we
      describe using crystallography, X-ray absorption spectroscopy, mutagenesis, mass
      spectrometry, and kinetic studies how GSTP1-1 recognizes the drug phenylarsine
      oxide (PAO). In conditions of cellular stress where glutathione (GSH) levels are
      low, PAO crosslinks C47 to C101 of the opposing monomer, a distance of 19.9 A,
      and causes a dramatic widening of the dimer interface by approximately 10 A. The
      GSH conjugate of PAO, which forms rapidly in cancerous cells, is a potent
      inhibitor (Ki  = 90 nM) and binds as a di-GSH complex in the active site forming
      part of a continuous network of interactions from one active site to the other.
      In summary, GSTP1-1 can detoxify arsenic-based drugs by sequestration at the
      active site and at the dimer interface, in situations where there is a plentiful
      supply of GSH, and at the reactive cysteines in conditions of low GSH.

PMID- 27863447
TI  - Hepatitis C virus infection triggers a tumor-like glutamine metabolism.
AB  - : Chronic infection with hepatitis C virus (HCV) is one of the main causes of
      hepatocellular carcinoma. However, the molecular mechanisms linking the infection
      to cancer development remain poorly understood. Here we used HCV-infected cells
      and liver biopsies to study how HCV modulates the glutaminolysis pathway, which
      is known to play an important role in cellular energetics, stress defense, and
      neoplastic transformation. Transcript levels of glutaminolytic factors were
      quantified in Huh7.5 cells or primary human hepatocytes infected with the
      Japanese fulminant hepatitis 1 HCV strain as well as in biopsies of chronic HCV
      patients. Nutrient deprivation, biochemical analysis, and metabolite
      quantification were performed with HCV-infected Huh7.5 cells. Furthermore, short
      hairpin RNA vectors and small molecule inhibitors were used to investigate the
      dependence of HCV replication on metabolic changes. We show that HCV modulates
      the transcript levels of key enzymes of glutamine metabolism in vitro and in
      liver biopsies of chronic HCV patients. Consistently, HCV infection increases
      glutamine use and dependence. We finally show that inhibiting glutamine
      metabolism attenuates HCV infection and the oxidative stress associated with HCV
      infection. CONCLUSION: Our data suggest that HCV establishes glutamine
      dependence, which is required for viral replication, and, importantly, that
      glutamine addiction is a hallmark of tumor cells. While HCV induces
      glutaminolysis to create an environment favorable for viral replication, it
      predisposes the cell to transformation. Glutaminolytic enzymes may be interesting
      therapeutic targets for prevention of hepatocarcinogenesis in chronic hepatitis
      C. (Hepatology 2017;65:789-803).

PMID- 27863448
TI  - Lipid zonation and phospholipid remodeling in nonalcoholic fatty liver disease.
AB  - : Nonalcoholic fatty liver disease (NAFLD) can progress from simple steatosis
      (i.e., nonalcoholic fatty liver [NAFL]) to nonalcoholic steatohepatitis (NASH),
      cirrhosis, and cancer. Currently, the driver for this progression is not fully
      understood; in particular, it is not known how NAFLD and its early progression
      affects the distribution of lipids in the liver, producing lipotoxicity and
      inflammation. In this study, we used dietary and genetic mouse models of NAFL and
      NASH and translated the results to humans by correlating the spatial distribution
      of lipids in liver tissue with disease progression using advanced mass
      spectrometry imaging technology. We identified several lipids with distinct zonal
      distributions in control and NAFL samples and observed partial to complete loss
      of lipid zonation in NASH. In addition, we found increased hepatic expression of
      genes associated with remodeling the phospholipid membrane, release of
      arachidonic acid (AA) from the membrane, and production of eicosanoid species
      that promote inflammation and cell injury. The results of our
      immunohistochemistry analyses suggest that the zonal location of remodeling
      enzyme LPCAT2 plays a role in the change in spatial distribution for AA
      containing lipids. This results in a cycle of AA-enrichment in pericentral
      hepatocytes, membrane release of AA, and generation of proinflammatory
      eicosanoids and may account for increased oxidative damage in pericentral regions
      in NASH. CONCLUSION: NAFLD is associated not only with lipid enrichment, but also
      with zonal changes of specific lipids and their associated metabolic pathways.
      This may play a role in the heterogeneous development of NAFLD. (Hepatology
      2017;65:1165-1180).

PMID- 27863449
TI  - IL6-mediated inflammatory loop reprograms normal to epithelial-mesenchymal
      transition+ metastatic cancer stem cells in preneoplastic liver of transforming
      growth factor beta-deficient beta2-spectrin+/- mice.
AB  - : Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related
      deaths worldwide with a poor survival rate. As many as 40% of HCCs are clonal,
      with alteration of key tumor-suppressor pathways in stem cells as the primary
      cause of HCC initiation. However, mechanisms that generate metastatic stem cells
      in preneoplastic liver tissue are not well understood. We hypothesized that
      chronic inflammation is a major driver of the transformation of genetically
      defective liver stem cells (LSCs) into highly metastatic liver cancer cells in
      premalignant liver tissue. We developed models of chronic inflammation in wild
      type (WT) and beta2-spectrin (beta2SP)+/- (SPTBN1) mice. CD133+ LSCs derived from
      preneoplastic livers of beta2SP+/- mice treated with interleukin-6 (pIL6; IL6
      beta2SP+/- LSCs) were highly tumorigenic and metastatic, whereas those derived
      from WT mice treated with pIL6 (IL6 WT LSCs) had significantly less proliferation
      and no tumorigenic properties. IL6 beta2SP+/- LSCs not only exhibited nuclear
      localization of Twist and Slug, markers of epithelial-mesenchymal transition
      (EMT), but also constitutive activation of nuclear factor kappa B (NFkappaB;
      RELA). Knockdown of NFkappaB decreased the EMT phenotypes and metastatic capacity
      of these cells. NFkappaB in IL6 beta2SP+/- LSCs was activated by transforming
      growth factor beta (TGFbeta)-activated kinase 1 (TAK1; MAP3K7), which is
      associated with poor survival in HCC and interleukin-6 (IL6) expression. The
      amount of constitutively activated NFkappaB increased dramatically from normal to
      cirrhotic to HCC tissues from human patients. CONCLUSION: IL6-mediated
      inflammation programs constitutive activation of the TAK1-NFkappaB signaling
      cascade in CD133+ LSCs, and this program interacts with deficient TGFbeta
      signaling, thereby accelerating the transformation of normal LSCs to metastatic
      cancer stem cells (mCSCs). Indeed, this study delineates the development of EMT
      positive mCSCs in HCC-free liver tissue upon chronic inflammation. (Hepatology
      2017;65:1222-1236).

PMID- 27863451
TI  - Cerebral white matter abnormalities in patients with charcot-marie-tooth disease.
AB  - Here, we report the structural evidence of cerebral white matter abnormalities in
      Charcot-Marie-Tooth (CMT) patients and the relationship between these
      abnormalities and clinical disability. Brain diffusion tensor imaging (DTI) was
      performed in CMT patients with demyelinating (CMT1A/CMT1E), axonal (CMT2A/CMT2E),
      or intermediate (CMTX1/DI-CMT) peripheral neuropathy. Although all patients had
      normal brain magnetic resonance imaging, all genetic subgroups except CMT1A had
      abnormal DTI findings indicative of significant cerebral white matter
      abnormalities: decreased fractional anisotropy and axial diffusivity, and
      increased radial diffusivity. DTI abnormalities were correlated with clinical
      disability, suggesting that there is comorbidity of central nervous system damage
      with peripheral neuropathy in CMT patients. ANN NEUROL 2017;81:147-151.

PMID- 27863452
TI  - Mutation in noncoding RNA RNU12 causes early onset cerebellar ataxia.
AB  - OBJECTIVE: Exome sequences account for only 2% of the genome and may overlook
      mutations causing disease. To obtain a more complete view, whole genome
      sequencing (WGS) was analyzed in a large consanguineous family in which members
      displayed autosomal recessively inherited cerebellar ataxia manifesting before 2
      years of age. METHODS: WGS from blood-derived genomic DNA was used for
      homozygosity mapping and a rare variant search. RNA from isolated blood
      leukocytes was used for quantitative polymerase chain reaction (PCR), RNA
      sequencing, and comparison of the transcriptomes of affected and unaffected
      family members. RESULTS: WGS revealed a point mutation in noncoding RNA RNU12
      that was associated with early onset cerebellar ataxia. The U12-dependent minor
      spliceosome edits 879 known transcripts. Reverse transcriptase PCR demonstrated
      minor intron retention in all of 9 randomly selected RNAs from this group, and
      RNAseq showed splicing disruption specific to all U12-type introns detected in
      blood monocytes from affected individuals. Moreover, 144 minor intron-containing
      RNAs were differentially expressed, including transcripts for 3 genes previously
      associated with cerebellar neurodegeneration. INTERPRETATION: Interference with
      particular spliceosome components, including small nuclear RNAs, cause
      reproducible uniquely distributed phenotypic and transcript-specific effects,
      making this an important category of disease-associated mutation. Our approach to
      differential expression analysis of minor intron-containing genes is applicable
      to other diseases involving altered transcriptome processing. ANN NEUROL
      2017;81:68-78.

PMID- 27863450
TI  - Interaction network of the ribosome assembly machinery from a eukaryotic
      thermophile.
AB  - Ribosome biogenesis in eukaryotic cells is a highly dynamic and complex process
      innately linked to cell proliferation. The assembly of ribosomes is driven by a
      myriad of biogenesis factors that shape pre-ribosomal particles by processing and
      folding the ribosomal RNA and incorporating ribosomal proteins. Biochemical
      approaches allowed the isolation and characterization of pre-ribosomal particles
      from Saccharomyces cerevisiae, which lead to a spatiotemporal map of biogenesis
      intermediates along the path from the nucleolus to the cytoplasm. Here, we cloned
      almost the entire set (~180) of ribosome biogenesis factors from the thermophilic
      fungus Chaetomium thermophilum in order to perform an in-depth analysis of their
      protein-protein interaction network as well as exploring the suitability of these
      thermostable proteins for structural studies. First, we performed a systematic
      screen, testing about 80 factors for crystallization and structure determination.
      Next, we performed a yeast 2-hybrid analysis and tested about 32,000 binary
      combinations, which identified more than 1000 protein-protein contacts between
      the thermophilic ribosome assembly factors. To exemplary verify several of these
      interactions, we performed biochemical reconstitution with the focus on the
      interaction network between 90S pre-ribosome factors forming the ctUTP-A and
      ctUTP-B modules, and the Brix-domain containing assembly factors of the pre-60S
      subunit. Our work provides a rich resource for biochemical reconstitution and
      structural analyses of the conserved ribosome assembly machinery from a
      eukaryotic thermophile.

PMID- 27863453
TI  - A new class of hepatitis B and D virus entry inhibitors, proanthocyanidin and its
      analogs, that directly act on the viral large surface proteins.
AB  - : Introduction of direct-acting antivirals against hepatitis C virus (HCV) has
      provided a revolutionary improvement in the treatment outcome. In contrast to
      HCV, however, the strategy for developing new antiviral agents against hepatitis
      B virus (HBV), especially viral-targeting compounds, is limited because HBV
      requires only four viral genes for its efficient replication/infection. Here, we
      identify an oligomeric flavonoid, proanthocyanidin (PAC) and its analogs, which
      inhibit HBV entry into host cells by targeting the HBV large surface protein
      (LHBs). Through cell-based chemical screening, PAC was identified to inhibit HBV
      infection with little cytotoxic effect. PAC prevented the attachment of the preS1
      region in the LHBs to its cellular receptor, sodium taurocholate cotransporting
      polypeptide (NTCP). PAC was shown to target HBV particles and impair their
      infectivity, whereas it did not affect the NTCP-mediated bile acid transport
      activity. Chemical biological techniques demonstrated that PAC directly
      interacted with the region essential for receptor binding in the preS1 region in
      the LHBs protein. Importantly, PAC had a pan-genotypic anti-HBV activity and was
      also effective against a clinically relevant nucleoside analog-resistant HBV
      isolate. We further showed that PAC augmented the ability of a nucleoside analog,
      tenofovir, to interrupt HBV spread over time in primary human hepatocytes by
      cotreatment. Moreover, derivative analysis could identify small molecules that
      demonstrated more-potent anti-HBV activity over PAC. CONCLUSION: PAC and its
      analogs represent a new class of anti-HBV agents that directly target the preS1
      region of the HBV large surface protein. These agents could contribute to the
      development of a potent, well-tolerated, and broadly active inhibitor of HBV
      infection. (Hepatology 2017;65:1104-1116).

PMID- 27863454
TI  - Sensory organisation and reactive balance control of amateur rugby players: A
      cross-sectional study.
AB  - PURPOSE: This study compared the sensory organisation and reactive balance
      control of amateur rugby players and a control group. METHODS: Forty-one amateur
      rugby players (22 males: 19 females; mean height +/- SD = 168.8 +/- 8.8 cm; mean
      weight +/- SD = 63.9 +/- 12.5 kg) and 31 control participants (22 males: 9
      females; mean height +/- SD = 171.5 +/- 10.3 cm; mean weight +/- SD = 63.8 +/-
      10.3 kg) completed the study. Their sensory organisation and standing balance
      performance were evaluated using a sensory organisation test (SOT), and their
      reactive balance performance was quantified using a motor control test (MCT). The
      SOT equilibrium scores (ES) and sensory ratios and the MCT motor response
      latencies were the major outcome measures. RESULTS: The results revealed that
      compared to the controls, amateur rugby players had lower SOT ESs under different
      sensory environments (P < .001, [Formula: see text] = 0.142-0.254) and prolonged
      reactive motor response times in the MCT (P < .001, d = 0.890). The vestibular
      and visual ratios were also lower in the rugby group (P = .005, [Formula: see
      text] = 0.107 and 0.108, respectively). No significant difference was found in
      the somatosensory ratio (P = .853, [Formula: see text] < 0.001) between the two
      groups. CONCLUSIONS: Amateur rugby players demonstrated inferior standing balance
      performance compared to their non-trained counterparts. They relied less heavily
      on vestibular and visual inputs to maintain standing balance under different
      sensory environments. In addition, they reacted more slowly to postural
      disturbance, reflecting their suboptimal reactive balance ability in standing.

PMID- 27863455
TI  - What Did We Learn from the Animal Studies of Body Weight-Supported Treadmill
      Training and Where Do We Go from Here?
AB  - Body weight-supported treadmill training (BWSTT) developed from animal studies of
      spinal cord injury (SCI). Evidence that spinal cats (i.e., cats that have a
      complete surgical transection of the cord) could regain the ability to step on a
      moving treadmill indicated a vast potential for spinal circuits to generate
      walking without the brain. BWSTT represented a means to unlock that potential. As
      the technique was adapted as a rehabilitation intervention for humans with SCI,
      shortcomings in the translation to walking in the real world were exposed.
      Evidence that BWSTT has not been as successful for humans with SCI leads us to
      revisit key animal studies. In this short review, we describe the task-specific
      nature of BWSTT and discuss how this specificity may pose limits on the recovery
      of overground walking. Also discussed are more recent studies that have
      introduced new strategies and tools that adapt BWSTT ideas to more functionally
      relevant tasks. We introduce a new device for weight-supported overground walking
      in rats called Circular BART (Body weight supported Ambulatory Rat Trainer) and
      demonstrate that it is relatively easy and inexpensive to produce. Future animal
      studies will benefit from the development of simple tools that facilitate
      training and testing of overground walking.

PMID- 27863456
TI  - A microplate reader-based method to quantify NADH-cytochrome b5 reductase
      activity for diagnosis of recessive congenital methaemoglobinemia.
AB  - OBJECTIVES: Congenital methemoglobinemia due to NADH-cytochrome b5 reductase 3
      (CYB5R3) deficiencies is an autosomal recessive disorder that occurs sporadically
      worldwide, A sensitive, accurate, and rapid analysis of NADH-CYB5R enzyme
      concentrations is necessary for the diagnosis of RCM. Here we present an
      alternative microplate method that is based on a standard 96-well microplate
      format and microplate reader that simplify the quantification of NADH-CYB5R
      activity. METHODS: TECAN (Infinite 200 PRO series) microplate reader with Tecan's
      proven MagellanTM software measured the NADH-CYB5R enzyme activity in 250 normal
      controls and previously diagnosed 25 cases of RCM due to NADH-CYB5R deficiency in
      the Indian population using 96-well microplates using 200 MUl of total reaction
      mixture and also compared with standard spectrophotometric assay. We have also
      studied stability of the hemolysate stored at 4 and -20 degrees C temperature.
      RESULTS AND DISCUSSION: Enzyme activity in all 25 samples ranged from 6.09 to
      10.07 IU/g Hb (mean +/- SD: 8.08 +/- 1.99 IU/g Hb) where as normal control ranged
      (n = 250) between 13.42 and 21.58 IU/g Hb) (mean +/- SD: 17.5 +/- 4.08 IU/g of
      Hb). Data obtained from the microplate reader were compared with standard
      spectrophotometer method and found 100% concordance using both methods.
      Microplate method allows differentiating between normal, deficient and
      intermediate enzyme activity. It was observed that samples had significant loss
      of activity when stored at 4 degrees C and retained stable activity at -20
      degrees C for 1 week time. CONCLUSION: Our new method, incorporating a whole
      process of enzyme assay into a microplate format is readily applicable and allows
      rapid monitoring of enzyme assay. It is readily applicable to quantitative assay
      on pediatric sample as well as large number of samples for population screening.

PMID- 27863457
TI  - The effects of high resistance-few repetitions and low resistance-high
      repetitions resistance training on climbing performance.
AB  - The aim of the study was to compare the effects of different strength training
      intensities on climbing performance, climbing-specific tests and a general
      strength test. Thirty lower grade and intermediate-level climbers participated in
      a 10-week training programme. The participants were randomized into three groups:
      high resistance-few repetitions training groups (HR-FR), low resistance-high
      repetitions training groups (LR-HR) and a control group (CON) which continued
      climbing/training as usual. Post-testing results demonstrated statistical
      tendencies for climbing performance improvements in the HR-FR and LR-HR (p =
      0.088-0.090, effect size = 0.55-0.73), but no differences were observed between
      the groups (p = 0.950). For the climbing-specific tests, no differences were
      observed between the groups (p = 0.507-1.000), but the HR-FR and LR-HR improved
      their time in both Dead-hang (p = 0.004-0.026) and Bent-arm hang (p < 0.001
      0.002). The HR-FR and LR-HR improved their 12RM strength in pull-down (p <=
      0.001), but not the CON group (p = 0.250). No differences were observed in the
      CON group in any of the tests (p = 0.190-0.596) with the exception of improvement
      in Bent-arm Hang (p = 0.018). The training groups reduced their climbing sessions
      during the intervention compared to the CON group (p = 0.057-0.074). In
      conclusion, HR-FR and LR-HR training programmes demonstrated an 11% and 12% non
      significant improvement in climbing performance despite a 50% reduction in
      climbing sessions, but improved the results in strength and climbing-specific
      tests. None of the training intensities was superior compared to the others.

PMID- 27863458
TI  - Benchtop and Initial Clinical Evaluation of the ShockPulse Stone Eliminator in
      Percutaneous Nephrolithotomy.
AB  - PURPOSE: Standardized bench testing of the new ShockPulseTM intracorporeal
      lithotripter was performed against three commercially available lithotripsy
      systems to determine differences and nuances in performance. MATERIALS AND
      METHODS: The ShockPulse intracorporeal lithotripter was tested against the LUS
      2TM, CyberWand,TM and EMS LithoClastTM in a standardized bench setting using hard
      (Ultracal-30) and soft (plaster of Paris) stone phantoms. An in vitro kidney
      model was used to record the time needed to fragment stone samples into
      retrievable-sized pieces. The time needed to fully comminute and evacuate stone
      samples was also recorded. The efficacy of each device at various applied
      pressures was determined using a hands-free apparatus, which was used to apply
      1.0, 1.5, and 2.0 pounds of fixed force. RESULTS: For hard and soft stones, the
      time needed to create retrievable fragments was similar among all systems (p =
      0.585). The ShockPulse was significantly faster than the LUS-2 and LithoClast at
      fully fragmenting and evacuating stone samples (p = 0.046), while the CyberWand
      was significantly slower than all three systems at this task (p = 0.001). When
      fixed forces were applied to a large stone phantom, the ShockPulse and CyberWand
      were significantly faster than the LUS-2 and LithoClast (p < 0.0001). When groups
      of smaller stones were tested, the ShockPulse was significantly faster at 1.0
      pound (p < 0.001) and 1.5 pounds (p < 0.002) of force. At 2.0 pounds, no
      differences were observed (p = 0.09). CONCLUSIONS: The ShockPulse is equally as
      effective and, in some circumstances, more effective than the three commercially
      available devices against which it was tested in an in vitro setting.

PMID- 27863460
TI  - The effects of a three-year integrated Olympic education programme on
      adolescents' prosocial behaviours.
AB  - The concept of Olympic education and its use of moral education to shape the
      development of personality have received insufficient empirical support. The aim
      of this study was to examine the effects of an integrated Olympic education
      programme on the development of prosocial behaviour in adolescents. A natural
      experimental research design was applied in this study. The pre-test sample
      included 411 adolescents (aged 13-14) who were randomly selected from schools
      that had begun to apply an integrated Olympic education programme, along with 430
      adolescents from schools without an Olympic education programme. The post-test
      sample included 381 students from schools implementing the Olympic education
      programme and 402 students from schools without an Olympic education programme.
      The revised prosocial tendencies measure was administered to the participants at
      pre- and post-test time points to assess changes in prosocial behaviour and
      specifically on six types of prosocial behaviour: public, anonymous, dire,
      emotional, compliant, and altruistic. The analyses showed significant
      improvements in prosocial behaviour in adolescents from schools that had
      implemented an integrated Olympic education programme. Changes in prosocial
      behaviour following the implementation of an integrated Olympic education
      programme were observed for the compliant, altruistic, and dire types of
      prosocial behaviour. In conclusion, these findings suggest that an integrated
      Olympic education programme effectively encourages prosocial behaviour in
      adolescents. This study expands our understanding of the efficiency of
      implementing an Olympic education programme in schools. We suggest that future
      research should investigate the behavioural changes in students of different ages
      from perspective of both teachers and students.

PMID- 27863459
TI  - Properties of Human Embryonic Stem Cells and Their Differentiated Derivatives
      Depend on Nonhistone DNA-Binding HMGB1 and HMGB2 Proteins.
AB  - HMGB1 and HMGB2 proteins have been implicated in numerous cellular processes,
      including proliferation, differentiation, apoptosis, and tumor growth. It is
      unknown whether they are involved in regulating the typical functions of
      pluripotent human embryonic stem cells (hESCs) and/or those of the differentiated
      derivatives of hESCs. Using inducible, stably transfected hESCs capable of shRNA
      mediated knockdown of HMGB1 and HMGB2, we provide evidence that downregulation of
      HMGB1 and/or HMGB2 in undifferentiated hESCs does not affect the stemness of
      cells and induces only minor changes to the proliferation rate, cell-cycle
      profile, and apoptosis. After differentiation is induced, however, the
      downregulation of those proteins has important effects on proliferation,
      apoptosis, telomerase activity, and the efficiency of differentiation toward the
      neuroectodermal lineage. Furthermore, those processes are affected only when one,
      but not both, of the two proteins is downregulated; the knockdown of both HMGB1
      and HMGB2 results in a normal phenotype. Those results advance our knowledge of
      regulation of hESC and human neuroectodermal cell differentiation and illustrate
      the distinct roles of HMGB1 and HMGB2 during early human development.

PMID- 27863462
TI  - Liver abscess and bacteremia caused by lactobacillus: role of probiotics? Case
      report and review of the literature.
AB  - BACKGROUND: Lactobacilli are non-spore forming, lactic acid producing, gram
      positive rods. They are a part of the normal gastrointestinal and genitourinary
      microbiota and have rarely been reported to be the cause of infections.
      Lactobacilli species are considered non-pathogenic organisms and have been used
      as probiotics to prevent antibiotic associated diarrhea. There are sporadic
      reported cases of infections related to lactobacilli containing probiotics. CASE
      PRESENTATION: In this paper we discuss a case of an 82 year old female with liver
      abscess and bacteremia from lactobacillus after using probiotics containing
      lactobacilli in the course of her treatment of Clostridium difficile colitis. The
      Lactobacillus strain identification was not performed and therefore, both
      commensal microbiota and the probiotic product should be considered as possible
      sources of the strain. CONCLUSION: Lactobacilli can lead to bacteremia and liver
      abscesses in some susceptible persons and greater awareness of this potential
      side effect is warranted with the increasing use of probiotics containing
      lactobacilli.

PMID- 27863461
TI  - Pooled genome wide association detects association upstream of FCRL3 with Graves'
      disease.
AB  - BACKGROUND: Graves' disease is an autoimmune thyroid disease of complex
      inheritance. Multiple genetic susceptibility loci are thought to be involved in
      Graves' disease and it is therefore likely that these can be identified by genome
      wide association studies. This study aimed to determine if a genome wide
      association study, using a pooling methodology, could detect genomic loci
      associated with Graves' disease. RESULTS: Nineteen of the top ranking single
      nucleotide polymorphisms including HLA-DQA1 and C6orf10, were clustered within
      the Major Histo-compatibility Complex region on chromosome 6p21, with rs1613056
      reaching genome wide significance (p = 5 * 10-8). Technical validation of top
      ranking non-Major Histo-compatablity complex single nucleotide polymorphisms with
      individual genotyping in the discovery cohort revealed four single nucleotide
      polymorphisms with p <= 10-4. Rs17676303 on chromosome 1q23.1, located upstream
      of FCRL3, showed evidence of association with Graves' disease across the
      discovery, replication and combined cohorts. A second single nucleotide
      polymorphism rs9644119 downstream of DPYSL2 showed some evidence of association
      supported by finding in the replication cohort that warrants further study.
      CONCLUSIONS: Pooled genome wide association study identified a genetic variant
      upstream of FCRL3 as a susceptibility locus for Graves' disease in addition to
      those identified in the Major Histo-compatibility Complex. A second locus
      downstream of DPYSL2 is potentially a novel genetic variant in Graves' disease
      that requires further confirmation.

PMID- 27863463
TI  - The ChIP-Seq tools and web server: a resource for analyzing ChIP-seq and other
      types of genomic data.
AB  - BACKGROUND: ChIP-seq and related high-throughput chromatin profilig assays
      generate ever increasing volumes of highly valuable biological data. To make
      sense out of it, biologists need versatile, efficient and user-friendly tools for
      access, visualization and itegrative analysis of such data. RESULTS: Here we
      present the ChIP-Seq command line tools and web server, implementing basic
      algorithms for ChIP-seq data analysis starting with a read alignment file. The
      tools are optimized for memory-efficiency and speed thus allowing for processing
      of large data volumes on inexpensive hardware. The web interface provides access
      to a large database of public data. The ChIP-Seq tools have a modular and
      interoperable design in that the output from one application can serve as input
      to another one. Complex and innovative tasks can thus be achieved by running
      several tools in a cascade. CONCLUSIONS: The various ChIP-Seq command line tools
      and web services either complement or compare favorably to related bioinformatics
      resources in terms of computational efficiency, ease of access to public data and
      interoperability with other web-based tools. The ChIP-Seq server is accessible at
      http://ccg.vital-it.ch/chipseq/ .

PMID- 27863464
TI  - Low wall shear stress is associated with the rupture of intracranial aneurysm
      with known rupture point: case report and literature review.
AB  - BACKGROUND: Few previous hemodynamic studies demonstrated the detailed features
      of rupture point of intracranial aneurysms. The hemodynamic simulation for the
      case that ruptured during angiography was even rare. In the present study, we
      studied the hemodynamic characteristics of a posterior communicating artery
      segment aneurysm that ruptured during angiography and detailed the hemodynamic
      features at the rupture point. CASE PRESENTATION: One 64-years-patient was 60-69
      years old and suffered a subarachnoid hemorrhage within 24 h. Standard digital
      subtraction angiography and three-dimensional (3D) rotational angiography were
      performed and an 8 mm left posterior communicating artery segment aneurysm was
      found. The patient had a seizure immediately following 3D angiography for about
      40 s and the immediate follow-up angiography showed contrast extravasation from
      the tip of identified aneurysms. The consequent vital sign of the patient became
      unstable. Urgent embolization under general anesthesia was planned, but the
      relatives refused interventional operation considering the high risk of procedure
      and poor condition of the patient. The computational fluid dynamic (CFD) method
      was used to evaluate the hemodynamic characteristics at rupture point, and the
      results showed that the rupture point was associated with markedly low wall shear
      stress and high oscillatory shear index without flow impingement. CONCLUSIONS: We
      present a rare case of which the rupture site was identified during angiography.
      The hemodynamic simulations revealed that the rupture point was associated with
      markedly low WSS and high OSI without flow impingement. The result may be unique
      to this particular aneurysm; however, our findings provide insight into the
      hemodynamics of rupture point.

PMID- 27863465
TI  - Bacillus species (BT42) isolated from Coffea arabica L. rhizosphere antagonizes
      Colletotrichum gloeosporioides and Fusarium oxysporum and also exhibits multiple
      plant growth promoting activity.
AB  - BACKGROUND: Colletotrichum and Fusarium species are among pathogenic fungi widely
      affecting Coffea arabica L., resulting in major yield loss. In the present study,
      we aimed to isolate bacteria from root rhizosphere of the same plant that is
      capable of antagonizing Colletotrichum gloeosporioides and Fusarium oxysporum as
      well as promotes plant growth. RESULTS: A total of 42 Bacillus species were
      isolated, one of the isolates named BT42 showed maximum radial mycelial growth
      inhibition against Colletotrichum gloeosporioides (78%) and Fusarium oxysporum
      (86%). BT42 increased germination of Coffee arabica L. seeds by 38.89%, decreased
      disease incidence due to infection of Colletotrichum gloeosporioides to 2.77% and
      due to infection of Fusarium oxysporum to 0 (p < 0.001). The isolate BT42 showed
      multiple growth-promoting traits. The isolate showed maximum similarity with
      Bacillus amyloliquefaciens. CONCLUSION: Bacillus species (BT42), isolated in the
      present work was found to be capable of antagonizing the pathogenic effects of
      Colletotrichum gloeosporioides and Fusarium oxysporum. The mechanism of action of
      inhibition of the pathogenic fungi found to be synergistic effects of secondary
      metabolites, lytic enzymes, and siderophores. The major inhibitory secondary
      metabolite identified as harmine (beta-carboline alkaloids).

PMID- 27863466
TI  - Brachial-ankle pulse wave velocity and metabolic syndrome in general population:
      the APAC study.
AB  - BACKGROUND: Metabolic syndrome (MetS) is correlated with arterial stiffness and
      can be evaluated by brachial-ankle pulse wave velocity (baPWV). We investigated
      potential associations between MetS and baPWV in a Chinese community population.
      METHODS: The community-based Asymptomatic Polyvascular Abnormalities in Community
      study examined asymptomatic polyvascular abnormalities in a Chinese population
      aged >=40 years. The relationship between MetS and its components and baPWV was
      analyzed by multivariate logistic and linear regression models. RESULTS: Out of
      5181 study participants, 1271 subjects (24.53%) had MetS. Mean values of baPWV in
      subjects with 0, 1, 2,3, 4, and 5 components of MetS were 1430, 1526, 1647,
      1676,1740, and 1860 cm/s, respectively (p < 0.001 for trend). After adjusting for
      confounding risk factors, MetS was significantly associated with baPWV (odds
      ratio [OR]: 2.74; 95% CI: 2.28, 3.30). Among the five components of MetS,
      elevated blood pressure was the most important factor for baPWV. All models of
      multivariate linear regression analysis showed a significant positive correlation
      between the increasing numbers of MetS components and baPWV (p < 0.0001).
      CONCLUSIONS: baPWV was associated with MetS and was greater with increasing
      numbers of MetS components. Elevated blood pressure was the most important factor
      for baPWV.

PMID- 27863467
TI  - Microarray analysis reveals a potential role of LncRNAs expression in cardiac
      cell proliferation.
AB  - BACKGROUND: Long non-coding RNAs (LncRNAs) have been identified to play important
      roles in epigenetic processes that underpin organogenesis. However, the role of
      LncRNAs in the regulation of transition from fetal to adult life of human heart
      has not been evaluated. METHODS: Immunofiuorescent staining was used to determine
      the extent of cardiac cell proliferation. Human LncRNA microarrays were applied
      to define gene expression signatures of the fetal (13-17 weeks of gestation, n =
      4) and adult hearts (30-40 years old, n = 4). Pathway analysis was performed to
      predict the function of differentially expressed mRNAs (DEM). DEM related to cell
      proliferation were selected to construct a lncRNA-mRNA co-expression network.
      Eight lncRNAs were confirmed by quantificational real-time polymerase chain
      reaction (n = 6). RESULTS: Cardiac cell proliferation was significant in the
      fetal heart. Two thousand six hundred six lncRNAs and 3079 mRNAs were found to be
      differentially expressed. Cell cycle was the most enriched pathway in down
      regulated genes in the adult heart. Eight lncRNAs (RP11-119 F7.5, AX747860,
      HBBP1, LINC00304, TPTE2P6, AC034193.5, XLOC_006934 and AL833346) were predicted
      to play a central role in cardiac cell proliferation. CONCLUSIONS: We discovered
      a profile of lncRNAs differentially expressed between the human fetal and adult
      heart. Several meaningful lncRNAs involved in cardiac cell proliferation were
      disclosed.

PMID- 27863468
TI  - The changing epidemiology of bacillary dysentery and characteristics of
      antimicrobial resistance of Shigella isolated in China from 2004-2014.
AB  - BACKGROUND: Bacillary dysentery caused by bacteria of the genus Shigella is a
      significant public health problem in developing countries such as China. The
      objective of this study was to analyze the epidemiological pattern of bacillary
      dysentery, the diversity of the causative agent, and the antimicrobial resistance
      patterns of Shigella spp. for the purpose of determining the most effective
      allocation of resources and prioritization of interventions. METHODS:
      Surveillance data were acquired from the National Infectious Disease Information
      Reporting System (2004-2014) and from the sentinel hospital-based surveillance
      system (2005-2014). We analyzed the spatial and temporal distribution of
      bacillary dysentery, age and sex distribution, species diversity, and
      antimicrobial resistance patterns of Shigella spp. RESULTS: The surveillance
      registry included over 3 million probable cases of bacillary dysentery during the
      period 2004-2014. The annual incidence rate of bacillary dysentery decreased from
      38.03 cases per 100,000 person-years in 2004 to 11.24 cases per 100,000 person
      years in 2014. The case-fatality rate decreased from 0.028% in 2004 to 0.003% in
      2014. Children aged <1 year and 1-4 years were most affected, with higher
      incidence rates (228.59 cases per 100,000 person-years and 92.58 cases per
      100,000 person-years respectively). The annual epidemic season occurred between
      June and September. A higher incidence rate of bacillary dysentery was found in
      the Northwest region, Beijing and Tianjin during the study period. Shigella
      flexneri was the most prevalent species that caused bacillary dysentery in China
      (63.86%), followed by Shigella sonnei (34.89%). Shigella isolates were highly
      resistant to nalidixic acid (89.13%), ampicillin (88.90%), tetracycline (88.43%),
      and sulfamethoxazole (82.92%). During the study period, isolates resistant to
      ciprofloxacin and cefotaxime increased from 8.53 and 7.87% in 2005 to 44.65 and
      29.94% in 2014, respectively. CONCLUSIONS: The incidence rate of bacillary
      dysentery has undergone an obvious decrease from 2004 to 2014. Priority
      interventions should be delivered to populations in northwest China and to
      individuals aged <5 years. Antimicrobial resistance of Shigella is a serious
      public health problem and it is important to consider the susceptibility profile
      of isolates before determining treatment.

PMID- 27863469
TI  - Changes in intraocular pressure values measured with noncontact tonometer (NCT),
      ocular response analyzer (ORA) and corvis scheimpflug technology tonometer (CST)
      in the early phase after small incision lenticule extraction (SMILE).
AB  - BACKGROUND: Corneal biomechanical properties are always compromised after corneal
      refractive surgeries thus leading to underestimated intraocular pressure (IOP)
      that complicates the management of IOP. We investigated the changes in
      postoperative baseline of IOP values measured with noncontact tonometer (NCT),
      ocular response analyzer (ORA) and corvis scheimpflug technology (CST) in the
      early phase after small incision lenticule extraction (SMILE). METHODS: Twenty
      two eyes (-6.76 +/- 1.39D) of 22 moderate and high myopes, (28.36 +/- 7.14 years,
      12 male and 10 female) were involved in this prospective study. IOP values were
      measured using a non-contact tomometer (NCT-IOP), an ocular response analyzer
      (corneal-compensated IOP, IOPcc and Goldmann-correlated IOP, IOPg) and a Corvis
      scheimpflug technology tonometer (CST-IOP) preoperatively, at 20 min and 24 h,
      postoperatively. Repeated measures analysis of variance (RM-ANOVA), Pearson's
      correlation analysis and multiple linear regression models (stepwise) were
      performed. Cut-off P values were 0.05. RESULTS: Except for IOPcc, NCT-IOP, IOPg,
      and CST-IOP values significantly decreased after SMILE procedure (All P values
      <0.05). DeltaCCT, as well as DeltaMRSE and DeltaKm, did not significantly
      correlated with DeltaNCT-IOP, DeltaIOPcc, DeltaIOPg or DeltaCST-IOP, (all P
      values >0.05). Multiple linear regression models (stepwise) showed that the
      practical post-operative IOP value was the main predictor of the theoretical post
      operative NCT-IOP, IOPcc and IOPg values (all P values <0.001). The postoperative
      applanation time 1 (AT1) value (B = 8.079, t = 4.866, P < 0.001), preoperative
      central corneal thickness (CCT) value (B = 0.035, t = 2.732, P = 0.014) and
      postoperative peak distance (PD) value (B = 0.515, t = 2.176, P = 0.043) were the
      main predictors of the theoretical post-operative CST-IOP value. CONCLUSIONS: IOP
      values are underestimated when assessed after SMILE by using NCT-IOP, IOPg and
      CST-IOP. The practical postoperative IOPcc value and theoretical post-operative
      CST-IOP value may be more preferable for IOP assessment in the early phase after
      SMILE. TRIAL REGISTRATION: Current Controlled Trials ChiCTRONRC13003114 .
      Retrospectively registered 17 March 2013.

PMID- 27863470
TI  - Transcript profiling for early stages during embryo development in Scots pine.
AB  - BACKGROUND: Characterization of the expression and function of genes regulating
      embryo development in conifers is interesting from an evolutionary point of view.
      However, our knowledge about the regulation of embryo development in conifers is
      limited. During early embryo development in Pinus species the proembyo goes
      through a cleavage process, named cleavage polyembryony, giving rise to four
      embryos. One of these embryos develops to a dominant embryo, which will develop
      further into a mature, cotyledonary embryo, while the other embryos, the
      subordinate embryos, are degraded. The main goal of this study has been to
      identify processes that might be important for regulating the cleavage process
      and for the development of a dominant embryo. RESULTS: RNA samples from embryos
      and megagametophytes at four early developmental stages during seed development
      in Pinus sylvestris were subjected to high-throughput sequencing. A total of 6.6
      million raw reads was generated, resulting in 121,938 transcripts, out of which
      36.106 contained ORFs. 18,638 transcripts were differentially expressed (DETs) in
      embryos and megagametophytes. GO enrichment analysis of transcripts up-regulated
      in embryos showed enrichment for different cellular processes, while those up
      regulated in megagametophytes were enriched for accumulation of storage material
      and responses to stress. The highest number of DETs was detected during the
      initiation of the cleavage process. Transcripts related to embryogenic
      competence, cell wall modifications, cell division pattern, axis specification
      and response to hormones and stress were highly abundant and differentially
      expressed during early embryo development. The abundance of representative DETs
      was confirmed by qRT-PCR analyses. CONCLUSION: Based on the processes identified
      in the GO enrichment analyses and the expression of the selected transcripts we
      suggest that (i) processes related to embryogenic competence and cell wall
      loosening are involved in activating the cleavage process; (ii) apical-basal
      polarization is strictly regulated in dominant embryos but not in the subordinate
      embryos; (iii) the transition from the morphogenic phase to the maturation phase
      is not completed in subordinate embryos. This is the first genome-wide transcript
      expression profiling of the earliest stages during embryo development in a Pinus
      species. Our results can serve as a framework for future studies to reveal the
      functions of identified genes.

PMID- 27863471
TI  - Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors
      of NSCLC A549 cell line in a synergistic way.
AB  - BACKGROUND: The study was designed to develop a platform to verify whether the
      extract of herbs combined with chemotherapy drugs play a synergistic role in anti
      tumor effects, and to provide experimental evidence and theoretical reference for
      finding new effective sensitizers. METHODS: Inhibition of tanshinone IIA and
      adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8
      assays. The combination index (CI) was calculated with the Chou-Talalay method,
      based on the median-effect principle. Migration and invasion ability of A549
      cells were determined by wound healing assay and transwell assay. Flow cytometry
      was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL
      staining was used to detect the apoptotic cells. Immunofluorescence staining was
      used to detect the expression of Cleaved Caspase-3. Western blotting was used to
      detect the proteins expression of relative apoptotic signal pathways. CDOCKER
      module in DS 2.5 was used to detect the binding modes of the drugs and the
      proteins. RESULTS: Both tanshinone IIA and adriamycin could inhibit the growth of
      A549, PC9, and HLF cells in a dose- and time-dependent manner, while the
      proliferative inhibition effect of tanshinone IIA on cells was much weaker than
      that of adriamycin. Different from the cancer cells, HLF cells displayed a
      stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA.
      When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a
      synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF
      cells. Tanshinone IIA combined with adriamycin could synergistically inhibit
      migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549
      cells. Both groups of the single drug treatment and the drug combination up
      regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the
      expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein.
      Compared with the single drug treatment groups, the drug combination groups were
      more statistically significant. The molecular docking algorithms indicated that
      tanshinone IIA could be docked into the active sites of all the tested proteins
      with H-bond and aromatic interactions, compared with that of adriamycin.
      CONCLUSIONS: Tanshinone IIA can be developed as a novel agent in the
      postoperative adjuvant therapy combined with other anti-tumor agents, and improve
      the sensibility of chemotherapeutics for non-small cell lung cancer with fewer
      side effects. In addition, this experiment can not only provide a reference for
      the development of more effective anti-tumor medicine ingredients, but also build
      a platform for evaluating the anti-tumor effects of Chinese herbal medicines in
      combination with chemotherapy drugs.

PMID- 27863472
TI  - The extent of using mobility assistive devices can partly explain fatigue among
      persons with late effects of polio - a retrospective registry study in Sweden.
AB  - BACKGROUND: Fatigue is reported as one of the most disabling symptoms and is
      common among persons living with late effects of polio. Although fatigue has been
      studied in the context of people living with late effects of polio, there is a
      lack of knowledge concerning the association of fatigue and variables of
      importance for participation in daily life. Therefore, the aim of this study was
      to explore possible factors associated with fatigue among persons with late
      effects of polio in Sweden. METHODS: This retrospective registry study consisted
      of 89 persons with late effects of polio living in Sweden. Fatigue was measured
      with the Multidimensional Fatigue Inventory (MFI-20) scale, Swedish version.
      Pearson's correlation coefficient was used to analyse the correlation between the
      factors and fatigue, and a multiple linear regression was carried out to explore
      factors for fatigue. RESULTS: Fatigue statistically significantly correlated with
      age (r = 0.234, p < 0.05) and the use of mobility assistive devices (r = 0.255, p
      < 0.05). The multiple linear regression model showed that the factors age (beta =
      0.304, p < 0.019) and mobility assistive devices (beta = 0.262, p < 0.017) were
      associated with fatigue among persons living with late effects of polio, and the
      model partly explained 14% of the variation of fatigue. CONCLUSIONS: Fatigue
      could partly be explained by the extent of using mobility assistive devices and
      age. Healthcare professionals should provide and demonstrate the importance of
      assistive devices to ensure management of fatigue in persons living with late
      effects of polio.

PMID- 27863473
TI  - ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle
      progression in primary breast cancer.
AB  - BACKGROUND: Anillin (ANLN), an actin-binding protein required for cytokinesis,
      has recently been presented as part of a prognostic marker panel in breast
      cancer. The objective of the current study was to further explore the prognostic
      and functional value of ANLN as a single biomarker in breast cancer. METHODS:
      Immunohistochemical assessment of ANLN protein expression was performed in two
      well characterized breast cancer cohorts (n = 484) with long-term clinical follow
      up data and the results were further validated at the mRNA level in a publicly
      available transcriptomics dataset. The functional relevance of ANLN was
      investigated in two breast cancer cell lines using RNA interference. RESULTS:
      High nuclear fraction of ANLN in breast tumor cells was significantly associated
      with large tumor size, high histological grade, high proliferation rate, hormone
      receptor negative tumors and poor prognosis in both examined cohorts.
      Multivariable analysis showed that the association between ANLN and survival was
      significantly independent of age in cohort I and significantly independent of
      proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size,
      ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN
      mRNA expression confirmed that high expression of ANLN was significantly
      correlated to poor overall survival in breast cancer patients. Consistent with
      the role of ANLN during cytokinesis, transient knock-down of ANLN protein
      expression in breast cancer cell lines resulted in an increase of senescent cells
      and an accumulation of cells in the G2/M phase of the cell cycle with altered
      cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA
      knockdown also resulted in decreased expression of cyclins D1, A2 and B1.
      CONCLUSIONS: ANLN expression in breast cancer cells plays an important role
      during cell division and a high fraction of nuclear ANLN expression in tumor
      cells is correlated to poor prognosis in breast cancer patients, independent of
      Ki-67, tumor size, hormone receptor status, HER2 status, nodal status and age.

PMID- 27863475
TI  - Spanish modified version of the palliative care outcome scale-symptoms renal:
      cross-cultural adaptation and validation.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) have a high symptoms
      burden that is related to a poor health-related quality of life (HRQoL) and high
      costs of care. Validated instruments may be useful for assessing the symptoms and
      monitoring outcomes in these patients. The Palliative care Outcome Scale-Symptoms
      Renal (POS-S Renal) is a patient-reported outcome measure for assessing symptoms
      in CKD stage 4-5. This study is the first cross-cultural adaptation and
      psychometric analysis of this clinical tool. The purpose of this study is to
      carry out a cross-cultural adaptation of the POS-S Renal for Spanish-speaking
      patients, and to perform an analysis of the psychometric properties of this
      questionnaire. METHODS: The English version of the POS-S Renal was culturally
      adapted and translated into Spanish using a double forward and backward method.
      An expert panel evaluated the content validity. The questionnaire was pilot
      tested in 30 patients. A total of 200 patients with CKD stage 4-5 filled in a
      modified Spanish version of the POS-S Renal and the MSAS-SF. Statistical analysis
      to evaluate the psychometric properties of the questionnaire was carried out.
      RESULTS: The content validity index (CVI) was 0.97, which indicated that the
      content of the instrument is an adequate reflection of the symptoms in advanced
      CKD (ACKD). The factor analysis indicated a two-factor solution explaining 35.05%
      of total variance. The confirmatory factor analysis (CFA) demonstrated that the
      two factor model was well supported (comparative fit index = 0.98, root mean
      square error of approximation = 0.068). This assessment tool demonstrated a
      satisfactory test-retest reliability (r = 0.909 to factor 1, r = 0.695 to factor
      2, r = 0.887 to total score), good internal consistency to factor 1 (alpha =
      0.78) and moderate internal consistency to factor 2 (alpha = 0.56). Concurrent
      criterion-related validity with MSAS-SF was also demonstrated, with r = 0.860,
      which indicated a high degree of correlation with a validated instrument that has
      been used in patients with ACKD. CONCLUSIONS: The Spanish modified version of the
      POS-S Renal is a reliable and valid instrument that can be used to assess
      symptoms in Spanish patients with CKD stage 4-5.

PMID- 27863474
TI  - Hypoxic resistance of KRAS mutant tumor cells to 3-Bromopyruvate is counteracted
      by Prima-1 and reversed by N-acetylcysteine.
AB  - BACKGROUND: The metabolic inhibitor 3-bromopyruvate (3-BrPA) is a promising anti
      cancer alkylating agent, shown to inhibit growth of some colorectal carcinoma
      with KRAS mutation. Recently, we demonstrated increased resistance to 3-BrPA in
      wt p53 tumor cells compared to those with p53 silencing or mutation. Since
      hypoxic microenvironments select for tumor cells with diminished therapeutic
      response, we investigated whether hypoxia unequally increases resistance to 3
      BrPA in wt p53 MelJuso melanoma harbouring (Q61L)-mutant NRAS and wt BRAF, C8161
      melanoma with (G12D)-mutant KRAS (G464E)-mutant BRAF, and A549 lung carcinoma
      with a KRAS (G12S)-mutation. Since hypoxia increases the toxicity of the p53
      activator, Prima-1 against breast cancer cells irrespective of their p53 status,
      we also investigated whether Prima-1 reversed hypoxic resistance to 3-BrPA.
      RESULTS: In contrast to the high susceptibility of hypoxic mutant NRAS MelJuso
      cells to 3-BrPA or Prima-1, KRAS mutant C8161 and A549 cells revealed hypoxic
      resistance to 3-BrPA counteracted by Prima-1. In A549 cells, Prima-1 increased
      p21CDKN1mRNA, and reciprocally inhibited mRNA expression of the SLC2A1-GLUT1
      glucose transporter-1 and ALDH1A1, gene linked to detoxification and stem cell
      properties. 3-BrPA lowered CAIX and VEGF mRNA expression. Death from joint Prima
      1 and 3-BrPA treatment in KRAS mutant A549 and C8161 cells seemed mediated by
      potentiating oxidative stress, since it was antagonized by the anti-oxidant and
      glutathione precursor N-acetylcysteine. CONCLUSIONS: This report is the first to
      show that Prima-1 kills hypoxic wt p53 KRAS-mutant cells resistant to 3-BrPA,
      partly by decreasing GLUT-1 expression and exacerbating pro-oxidant stress.

PMID- 27863476
TI  - Is immunohistochemistry of BRAF V600E useful as a screening tool and during
      progression disease of melanoma patients?
AB  - BACKGROUND: In clinical practice the gold standard method to assess BRAF status
      in patients with metastatic melanoma is based on molecular assays. Recently, a
      mutation-specific monoclonal antibody (VE1), which detects the BRAF V600E mutated
      protein, has been developed. With this study we aimed to confirm the clinical
      value of the VE1 Ventana(r) antibody, as today a univocal validated and
      accredited immunohistochemical procedure does not exist, to preliminary detect
      BRAF status in our routine diagnostic procedures. Moreover, we explored the
      biological meaning of BRAF immunohistochemical labeling both as a predictor
      marker of response to target therapy and, for the first time, as a player of
      acquired tumor drug resistance. METHODS: We analyzed a retrospective series of 64
      metastatic melanoma samples, previously investigated for molecular BRAF status,
      using a fully automatized immunohistochemical method. We correlated the data to
      the clinicopathologic characteristics of patients and their clinical outcome.
      RESULTS: The sensitivity and the specificity of the Ventana(r) VE1 antibody were
      89.2 and 96.2% respectively, while the positive predictive value and negative
      predictive value were 97.1 and 86.2%, respectively. For six mutated patients the
      histological sample before treatment and when disease progressed was available.
      The immunohistochemical BRAF V600E expression in the specimens when disease
      progressed was less intense and more heterogeneous compared to the basal
      expression. Multivariate analysis revealed that a less intense grade of positive
      expression is an independent predictor of a less aggressive stage at diagnosis (p
      = 0.0413). CONCLUSIONS: Our findings encourage the introduction of
      immunohistochemistry as a rapid screening tool for the assessment of BRAF status
      in melanoma patients in routine diagnostic procedures and prepare the ground for
      other studies to highlight the role of immunohistochemical BRAF V600E expression
      in patients at the time of progression.

PMID- 27863477
TI  - Keratin 19 as a key molecule in progression of human hepatocellular carcinomas
      through invasion and angiogenesis.
AB  - BACKGROUND: Keratin (K) 19-positive hepatocellular carcinoma (HCC) is well known
      to have a higher malignant potential than K19-negative HCC: However, the
      molecular mechanisms involved in K19-mediated progression of HCC remain unclear.
      We attempted to clarify whether K19 directly affects cell survival and
      invasiveness in association with cellular senescence or epithelial-mesenchymal
      transition (EMT) in K19-positive HCC. METHODS: K19 expression was analysed in 136
      HCC surgical specimens. The relationship of K19 with clinicopathological factors
      and survival was analysed. Further, the effect of K19 on cell proliferation,
      invasion, and angiogenesis was examined by silencing K19 in the human HCC cell
      lines, HepG2, HuH-7, and PLC/PRF/5. Finally, we investigated HCC invasion,
      proliferation, and angiogenesis using K19-positive HCC specimens. RESULTS:
      Analysis of HCC surgical specimens revealed that K19-positive HCC exhibited
      higher invasiveness, metastatic potential, and poorer prognosis. In vitro
      experiments using the human HCC cell lines revealed that K19 silencing suppressed
      cell growth by inducting apoptosis or upregulating p16 and p27, resulting in
      cellular senescence. In addition, transfection with K19 siRNA upregulated E
      cadherin gene expression, significantly inhibited the invasive capacity of the
      cells, downregulated angiogenesis-related molecules such as vasohibin-1 (VASH1)
      and fibroblast growth factor 1 (FGFR1), and upregulated vasohibin-2 (VASH2). K19
      positive HCC specimens exhibited a high MIB-1 labelling index, decreased E
      cadherin expression, and high microvessel density around cancer foci. CONCLUSION:
      K19 directly promotes cancer cell survival, invasion, and angiogenesis, resulting
      in HCC progression and poor clinical outcome. K19 may therefore be a novel drug
      target for the treatment of K19-positive HCC.

PMID- 27863478
TI  - Prognostic value of CD66b positive tumor-infiltrating neutrophils in testicular
      germ cell tumor.
AB  - BACKGROUND: Prognostic value of immune cells is not clear in testicular germ cell
      tumors (TGCTs). We aimed to investigate the prognostic value of tumor
      infiltrating neutrophils in TGCTs. METHODS: A total of 102 patients who underwent
      orchiectomy for TGCT were investigated for CD66b positive tumor-infiltrating
      neutrophils (CD66b + TINs). Immmunostaining for CD66b was performed in 102
      sections as described. Clinicopathological parameters as well as cancer specific
      survival and overall survival were assessed for correlation with CD66b + TIN
      density. RESULTS: High density group was significantly correlated with tumor
      diameter >= 10 cm, presence of nodal/distant metastasis, S stage, diagnosis of
      nonseminomatous germ cell tumor (NGCT), and presence of venous invasion (p =
      0.0198, p < 0.0001, p = 0.0275, p = 0.0004, and p = 0.0287, respectively). It was
      also significantly associated with cancer-specific and overall survival (logrank
      p = 0.0036, and p = 0.0002, respectively). Multivariate analysis showed that
      increased CD66b + TIN was an independent prognostic factor for overall survival
      (p = 0.0095). CONCLUSIONS: Increased CD66b + TIN was significantly associated
      with presence of metastasis, S stage, and nonseminomatous germ cell tumor
      diagnosis. It was also an independent prognostic factor of overall survival in
      patients with TGCT.

PMID- 27863479
TI  - Myasthenic symptoms in anti-low-density lipoprotein receptor-related protein 4
      antibody-seropositive amyotrophic lateral sclerosis: two case reports.
AB  - BACKGROUND: Myasthenic symptoms can be present in patients with amyotrophic
      lateral sclerosis (ALS). These symptoms have been considered to be caused by the
      degeneration of distal motor neurons and the neuromuscular junction (NMJ). Recent
      studies suggested that antibody to low-density lipoprotein receptor-related
      protein 4 (LRP4) was a pathogenic agent of myasthenia gravis (MG), and it was
      also detected in ALS patients. CASE PRESENTATION: Patient 1: A 58-year-old
      Japanese man developed progressive weakness and subsequent myasthenic symptoms
      including oculomotor disturbance. Clinical examination and electrophysiological
      studies confirmed upper and lower motor neuron involvement and NMJ dysfunction,
      and anti-LRP4 antibody was detected in his serum. A series of immunotherapies,
      including steroid pulse therapy, intravenous immunoglobulin, and plasmapheresis,
      was performed, and the myasthenic symptoms partially improved. The titer of anti
      LRP4 antibody subsequently decreased. However, the therapeutic effect was
      transient, and ALS symptoms progressed. His clinical findings fulfilled the
      criteria of probable ALS using the Awaji criteria. Patient 2: A 74-year-old
      Japanese man suffered from progressive weakness of all limbs and dropped head in
      the evening. He complained of diplopia with a lateral horizontal gaze. Probable
      ALS was diagnosed because of the upper and lower motor neuron signs, whereas anti
      LRP4 antibody was detected. Several immunotherapies were administered, and the
      myasthenic symptoms partially responded to each therapy. However, the truncal
      muscle weakness progressed, and he died of respiratory failure. CONCLUSION: We
      report two anti-LRP4 antibody-seropositive ALS patients with myasthenia who were
      not typical of ALS patients, and showed partial responses to immunotherapies. The
      anti-LRP4 antibody-seropositive status may influence developing ALS and cause
      additional ALS symptoms.

PMID- 27863480
TI  - Effects of lifestyle intervention using patient-centered cognitive behavioral
      therapy among patients with cardio-metabolic syndrome: a randomized, controlled
      trial.
AB  - BACKGROUND: Cardio-metabolic syndrome (CMS) is a highly prevalent condition.
      There is an urgent need to identify effective and integrated multi-disciplinary
      approaches that can reduce risk factors for CMS. METHODS: Sixty-two patients with
      a history of CMS were randomized 1:1 into two groups: a standard information 
      only group (control), or a self-regulated lifestyle waist circumference (patient
      centered cognitive behavioral therapy) intervention group. A pretest and
      posttest, controlled, experimental design was used. Outcomes were measured at the
      baseline (week 0) and at the end of intervention (week 12). Comparisons were
      drawn between groups and over time. RESULTS: The mean (standard deviation) age of
      the subjects was 48.6 (5.8) years ranging from 32 to 63, and 56.9% of the
      participants were female. Both groups showed no significant differences in
      Demographic variables and the metabolic syndrome indicators at baseline. While
      the control group only showed modest improvement after 12 weeks, compared to
      baseline, the intervention group demonstrated significant improvement from
      baseline. This study controlled for patients' demographics and baseline
      characteristics when assessing the effects of intervention. After adjusting for
      age, education and baseline level, the experimental group and the control group
      were statistically significant different in the following post-treatment
      outcomes: WC (F = 35.96, P < 0.001), TG (F = 18.93, P < 0.001), RSBP (F = 33.89,
      P < 0.001) and SF-36(F = 157.93, P < 0.001). The results showed patients' age and
      education were not strong predictors of patients' outcome (including WC, TG, RSBP
      and SF-36). CONCLUSIONS: Lifestyle intervention on patient-centered cognitive
      behavioral therapy can improve the physical and mental health conditions among
      individuals reporting a history of cardio-metabolic syndrome, and possibly
      provided preliminary benefits for the treatment of CMS. TRIAL REGISTRATION:
      Chinese Clinical Trial Register #, ChiCTR15006148 .

PMID- 27863481
TI  - Association of nutritional status-related indices and chemotherapy-induced
      adverse events in gastric cancer patients.
AB  - BACKGROUND: Malnutrition in gastrectomized patients receiving chemotherapy is
      associated with the susceptibility to chemotherapy-related adverse events. This
      study evaluated pre-operative nutritional status-related indices associated with
      adverse events in post-operation gastric cancer patients receiving chemotherapy.
      METHODS: Medical records of 234 gastrectomized patients under adjuvant
      tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were
      analyzed. Nutritional status assessment included Patient-Generated Subjective
      Global Assessment (PG-SGA), body weight, body mass index, serum albumin
      concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse
      events were determined using Common Terminology Criteria for Adverse Events.
      RESULTS: PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the
      patients revealed serious malnutrition with PG-SGA score of >=9. Fifteen % of
      patients lost >=10% of the initial body weight, 14.5% of the patients had
      hypoalbuminemia (<3.5 g/dL), and 66.2% had NRI score less than 97.5 indicating
      moderate to severe malnutrition. Hematological adverse events were present in 94%
      (>=grade 1) and 16.2% (>=grade 3). Non-hematological adverse events occurred in
      95.7% (>=grade1) and 16.7% (>=grade 3) of the patients. PG-SGA and NRI score was
      not associated with treatment-induced adverse events. Multivariate analyses
      indicated that female, low body mass index, and hypoalbuminemia were independent
      risk factors for grade 3/4 hematological adverse events. Age was an independent
      risk factor for grade 3/4 non-hematological adverse events. Neutropenia was the
      most frequently occurring adverse event, and associated risk factors were female,
      total gastrectomy, and hypoalbuminemia. CONCLUSIONS: Hypoalbuminemia, not PG-SGA
      or NRI may predict chemotherapy-induced adverse events in gastrectomized cancer
      patients.

PMID- 27863482
TI  - In silico SNP analysis of the breast cancer antigen NY-BR-1.
AB  - BACKGROUND: Breast cancer is one of the most common malignancies with increasing
      incidences every year and a leading cause of death among women. Although early
      stage breast cancer can be effectively treated, there are limited numbers of
      treatment options available for patients with advanced and metastatic disease.
      The novel breast cancer associated antigen NY-BR-1 was identified by SEREX
      analysis and is expressed in the majority (>70%) of breast tumors as well as
      metastases, in normal breast tissue, in testis and occasionally in prostate
      tissue. The biological function and regulation of NY-BR-1 is up to date unknown.
      METHODS: We performed an in silico analysis on the genetic variations of the NY
      BR-1 gene using data available in public SNP databases and the tools SIFT,
      Polyphen and Provean to find possible functional SNPs. Additionally, we
      considered the allele frequency of the found damaging SNPs and also analyzed data
      from an in-house sequencing project of 55 breast cancer samples for recurring
      SNPs, recorded in dbSNP. RESULTS: Over 2800 SNPs are recorded in the dbSNP and
      NHLBI ESP databases for the NY-BR-1 gene. Of these, 65 (2.07%) are synonymous
      SNPs, 191 (6.09%) are non-synoymous SNPs, and 2430 (77.48%) are noncoding
      intronic SNPs. As a result, 69 non-synoymous SNPs were predicted to be damaging
      by at least two, and 16 SNPs were predicted as damaging by all three of the used
      tools. The SNPs rs200639888, rs367841401 and rs377750885 were categorized as
      highly damaging by all three tools. Eight damaging SNPs are located in the
      ankyrin repeat domain (ANK), a domain known for its frequent involvement in
      protein-protein interactions. No distinctive features could be observed in the
      allele frequency of the analyzed SNPs. CONCLUSION: Considering these results we
      expect to gain more insights into the variations of the NY-BR-1 gene and their
      possible impact on giving rise to splice variants and therefore influence the
      function of NY-BR-1 in healthy tissue as well as in breast cancer.

PMID- 27863483
TI  - Estimation of tulathromycin depletion in plasma and milk after subcutaneous
      injection in lactating goats using a nonlinear mixed-effects pharmacokinetic
      modeling approach.
AB  - BACKGROUND: Extra-label use of tulathromycin in lactating goats is common and may
      cause violative residues in milk. The objective of this study was to develop a
      nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin
      depletion in plasma and milk of lactating goats. Eight lactating goats received
      two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and
      milk samples were analyzed for concentrations of tulathromycin and the common
      fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively,
      using liquid chromatography mass spectrometry. Based on these new data and
      related literature data, a NLME-PK compartmental model with first-order
      absorption and elimination was used to model plasma concentrations and cumulative
      excreted amount in milk. Monte Carlo simulations with 100 replicates were
      performed to predict the time when the upper limit of the 95% confidence interval
      of milk concentrations was below the tolerance. RESULTS: All animals were healthy
      throughout the study with normal appetite and milk production levels, and with
      mild-moderate injection-site reactions that diminished by the end of the study.
      The measured data showed that milk concentrations of the marker residue of
      tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after
      the second injection. A 2-compartment model with milk as an excretory compartment
      best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The
      model-predicted data correlated with the measured data very well. The NLME-PK
      model estimated that tulathromycin plasma concentrations were below LOD (1.2
      ng/ml) 43 days after a single injection, and 62 days after the second injection
      with a 95% confidence. These estimated times are much longer than the current
      meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating
      cattle. CONCLUSIONS: The results suggest that twice subcutaneous injections of
      2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach
      for treating pulmonary infections in lactating goats, but a prolonged withdrawal
      time of at least 39 days after the second injection should be considered to
      prevent violative residues in milk and any dairy goat being used for meat should
      have an extended meat withdrawal time.

PMID- 27863484
TI  - Methods used to address fidelity of receipt in health intervention research: a
      citation analysis and systematic review.
AB  - BACKGROUND: The American Behaviour Change Consortium (BCC) framework acknowledges
      patients as active participants and supports the need to investigate the fidelity
      with which they receive interventions, i.e. receipt. According to this framework,
      addressing receipt consists in using strategies to assess or enhance
      participants' understanding and/or performance of intervention skills. This
      systematic review aims to establish the frequency with which receipt is addressed
      as defined in the BCC framework in health research, and to describe the methods
      used in papers informed by the BCC framework and in the wider literature.
      METHODS: A forward citation search on papers presenting the BCC framework was
      performed to determine the frequency with which receipt as defined in this
      framework was addressed. A second electronic database search, including search
      terms pertaining to fidelity, receipt, health and process evaluations was
      performed to identify papers reporting on receipt in the wider literature and
      irrespective of the framework used. These results were combined with forward
      citation search results to review methods to assess receipt. Eligibility criteria
      and data extraction forms were developed and applied to papers. Results are
      described in a narrative synthesis. RESULTS: 19.6% of 33 studies identified from
      the forward citation search to report on fidelity were found to address receipt.
      In 60.6% of these, receipt was assessed in relation to understanding and in 42.4%
      in relation to performance of skill. Strategies to enhance these were present in
      12.1% and 21.1% of studies, respectively. Fifty-five studies were included in the
      review of the wider literature. Several frameworks and operationalisations of
      receipt were reported, but the latter were not always consistent with the guiding
      framework. Receipt was most frequently operationalised in relation to
      intervention content (16.4%), satisfaction (14.5%), engagement (14.5%), and
      attendance (14.5%). The majority of studies (90.0%) included subjective
      assessments of receipt. These relied on quantitative (76.0%) rather than
      qualitative (42.0%) methods and studies collected data on intervention recipients
      (50.0%), intervention deliverers (28.0%), or both (22.0%). Few studies (26.0%)
      reported on the reliability or validity of methods used. CONCLUSIONS: Receipt is
      infrequently addressed in health research and improvements to methods of
      assessment and reporting are required.

PMID- 27863485
TI  - Potential effects of samsum ant, Brachyponera sennaarensis, venom on TNF-alpha/NF
      kappaB mediated inflammation in CCL4-toxicity in vivo.
AB  - BACKGROUND: Ant venom shows antimicrobial, anti-parasitic and anti-inflammatory
      activities, both in vitro and in vivo. Our recent studies have confirmed the role
      of samsum ant venom (SAV) as a powerful antioxidant. This study aimed to
      investigate whether SAV as a potential treatment for CCl4-induced acute liver
      toxicity in an animal (rat) model. METHODS: Thirty-two rats were assigned into
      four groups; the first one served as the control. The second group received a
      single dose of 1 ml/kg CCl4 in a 1:1 ratio with olive oil through an
      intraperitoneal injection. The third group received a single dose of 1 ml/kg CCl4
      and then treated with SAV at a dose of 100 MUg SAV twice a week for three weeks.
      The fourth group received a dose of 100 MUg SAV only twice a week for three
      weeks. ELISA, RT-PCR and histopathological examinations were applied. RESULTS:
      Results showed that antioxidant enzymes were significantly reduced in the
      diseased animals. SAV was found to significantly restore the oxidative stability
      in diseased animals. ELISA estimation and RT-PCR analysis also showed significant
      upregulation of both nuclear factor (kappaB) NF-kappaB and inhibitor (kappaB)
      IkappaB, respectively, in the diseased animals compared to the normal ones. The
      expression of tumour necrosis factor alpha (TNF-alpha) and pro-apoptotic receptor
      (Fas) were also significantly up-regulated in the diseased rats. Interestingly,
      SAV was found to significantly restore NF-kappaB, IkappaB and TNF-alpha in the
      diseased rats to the normal values. As a result, liver enzymes, serum proteins
      and lipid concentrations were significantly improved by SAV in CCl4-animals in
      comparison with the control ones. Moreover, SAV obviously improved the hepatic
      tissues of the same group was. CONCLUSION: SAV treatment restores the normal
      biochemical and oxidative stability by improving the TNF-alpha/NF-kappaB mediated
      inflammation in CCL4-treated rats.

PMID- 27863486
TI  - Costs of conservative management of early-stage prostate cancer compared to
      radical prostatectomy-a claims data analysis.
AB  - BACKGROUND: Due to widespread PSA testing incidence rates of localized prostate
      cancer increase but curative treatment is often not required. Overtreatment
      imposes a substantial economic burden on health care systems. We compared the
      direct medical costs of conservative management and radical therapy for the
      management of early-stage prostate cancer in routine care. METHODS: An
      observational study design is chosen based on claims data of a German statutory
      health insurance fund for the years 2008-2011. Three hundred fifty-three age
      matched men diagnosed with prostate cancer and treated with conservative
      management and radical prostatectomy, are included. Individuals with diagnoses of
      metastases or treatment of advanced prostate cancer are excluded. In an excess
      cost approach direct medical costs are considered from an insured community
      perspective for in- and outpatient care, pharmaceuticals, physiotherapy, and
      assistive technologies. Generalized linear models adjust for comorbidity by
      Charlson comorbidity score and recycled predictions method calculates per capita
      costs per treatment strategy. RESULTS: After follow-up of 2.5 years per capita
      costs of conservative management are ?6611 lower than costs of prostatectomy ([
      9734;-3547], p < 0.0001). Complications increase costs of assistive technologies
      by 30% (p = 0.0182), but do not influence any other costs. Results are robust to
      cost outliers and incidence of prostate cancer diagnosis. The short time horizon
      does not allow assessing long-term consequences of conservative management.
      CONCLUSIONS: At a time horizon of 2.5 years, conservative management is
      preferable to radical prostatectomy in terms of costs. Claims data analysis is
      limited in the selection of comparable treatment groups, as clinical information
      is scarce and bias due to non-randomization can only be partly mitigated by
      matching and confounder adjustment.

PMID- 27863487
TI  - Analyses of density-dependent effects are needed to understand how and when
      Wolbachia can control dengue vectors.
AB  - Releases of Wolbachia-infected mosquitoes have been shown to be an effective
      method of controlling Aedes aegypti, the main vector of dengue fever, in
      Australia. A study in BMC Biology from Penelope Hancock and others shows that
      incorporation of density-dependent effects into population models can provide
      major improvements in understanding how and when the infected populations can
      become established.See research article:
      https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0319-5 .

PMID- 27863489
TI  - The effect of cumulative glycemic burden on the incidence of diabetic foot
      disease.
AB  - BACKGROUND: Glycemic control is a known modifiable risk factor for diabetic foot
      disease. Prior attempts to define its relationship with diabetic foot ulcer and
      Charcot arthropathy fail to account for variability in control and duration of
      diabetic disease. We developed a novel metric to reflect aggregate disease
      exposure in a diabetic, termed cumulative glycemic burden. We hypothesized that
      it would be positively associated with both diabetic foot ulcer and
      radiographically diagnosed Charcot arthropathy. METHODS: Patients aged 18 to 90
      years with >=3 hemoglobin A1c (HbA1c) values were identified retrospectively at a
      single institution over a 15-year period. Primary outcomes were ICD-9 diagnosis
      of foot ulcer and radiographically diagnosed Charcot arthropathy. Cumulative
      glycemic burden was calculated by trapezoidal integration of the area under a
      curve defined by HbA1c values above 7 over time. Patients were stratified into
      quartiles based on cumulative glycemic burden (excellent, good, fair, and poor
      control). chi 2 tests compared the proportion of foot ulcer and Charcot across
      quartiles. Regression analysis identified associated demographic and comorbidity
      factors with diabetic foot disease. Statistical significance was set at P < .05.
      RESULTS: Out of 22,913 diabetics, 1643 (7.2%) had a foot ulcer; 54 out of 771
      diabetics (7.0%) had radiographic Charcot arthropathy. There was a statistically
      significant stepwise increase in the incidence of foot ulcer with increasing
      cumulative glycemic burden by patient quartile (5.2 vs. 6.4 vs. 7.9 vs. 13.9%; P
      < .001). No significant trend was seen between incidence of Charcot arthropathy
      and greater cumulative glycemic burden (7.8 vs. 5.6 vs. 4.4 vs. 10.0%; P = .469).
      Peripheral vascular disease was most strongly associated with diabetic foot
      ulcer. Hypertension and diabetic neuropathy were independently associated with
      Charcot arthropathy. CONCLUSIONS: Increasing cumulative glycemic burden is
      positively associated with diabetic foot ulcer. Greater attention should be paid
      towards the most poorly controlled diabetics with the longest duration of disease
      to reduce their risk. Cumulative glycemic burden is not associated with Charcot
      arthropathy.

PMID- 27863488
TI  - Mathematical model on Alzheimer's disease.
AB  - BACKGROUND: Alzheimer disease (AD) is a progressive neurodegenerative disease
      that destroys memory and cognitive skills. AD is characterized by the presence of
      two types of neuropathological hallmarks: extracellular plaques consisting of
      amyloid beta-peptides and intracellular neurofibrillary tangles of
      hyperphosphorylated tau proteins. The disease affects 5 million people in the
      United States and 44 million world-wide. Currently there is no drug that can
      cure, stop or even slow the progression of the disease. If no cure is found, by
      2050 the number of alzheimer's patients in the U.S. will reach 15 million and the
      cost of caring for them will exceed $ 1 trillion annually. RESULTS: The present
      paper develops a mathematical model of AD that includes neurons, astrocytes,
      microglias and peripheral macrophages, as well as amyloid beta aggregation and
      hyperphosphorylated tau proteins. The model is represented by a system of partial
      differential equations. The model is used to simulate the effect of drugs that
      either failed in clinical trials, or are currently in clinical trials.
      CONCLUSIONS: Based on these simulations it is suggested that combined therapy
      with TNF- alpha inhibitor and anti amyloid beta could yield significant efficacy
      in slowing the progression of AD.

PMID- 27863491
TI  - The Year of the Wisent.
AB  - Delving into European prehistory, two recent studies analyze ancient DNA from
      bison species depicted by our ancestors on the walls of their caves. The DNA
      tells a story of migrations driven by climate change but leaves some mystery
      clouding the genetic descent and climate preference of the still-extant wisent,
      otherwise known as the European bison.See research articles:
      https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0317-7
      http://www.nature.com/articles/ncomms13158.

PMID- 27863490
TI  - Suberoylanilide hydroxamic acid represses glioma stem-like cells.
AB  - BACKGROUND: Glioma stem-like cells (GSCs) are proposed to be responsible for high
      resistance in glioblastoma multiforme (GBM) treatment. In order to find new
      strategies aimed at reducing GSC stemness and improving GBM patient survival, we
      investigated the effects and mechanism of a histone deacetylases (HDACs)
      inhibitor, suberoylanilide hydroxamic acid (SAHA), since HDAC activity has been
      linked to cancer stem-like cell (CSC) abundance and properties. METHODS: Human
      GBM cell lines were plated in serum-free suspension cultures allowed for sphere
      forming and CSC enrichment. Subsequently, upon SAHA treatment, the stemness
      markers, cell proliferation, and viability of GSCs as well as cellular apoptosis
      and senescence were examined in order to clarify whether inhibition of GSCs
      occurs. RESULTS: We demonstrated that SAHA attenuated cell proliferation and
      diminished the expression stemness-related markers (CD133 and Bmi1) in GSCs.
      Furthermore, at high concentrations (more than 5 MUM), SAHA triggered apoptosis
      of GSCs accompanied by increases in both activation of caspase 8- and caspase 9
      mediated pathways. Interestingly, we found that a lower dose of SAHA (1 MUM and
      2.5 MUM) inhibited GSCs via cell cycle arrest and induced premature senescence
      through p53 up-regulation and p38 activation. CONCLUSION: SAHA induces apoptosis
      and functions as a potent modulator of senescence via the p38-p53 pathway in
      GSCs. Our results provide a perspective on targeting GSCs via SAHA treatment, and
      suggest that SAHA could be used as a potent agent to overcome drug resistance in
      GBM patients.

PMID- 27863492
TI  - Defective autophagy leads to the suppression of stem-like features of CD271+
      osteosarcoma cells.
AB  - BACKGROUND: As an important stress-response mechanism, autophagy plays crucial
      role in the tumor formation and drug resistance of cancer cells including
      osteosarcoma (OS). OS cancer stem cells (CSCs) also are considered a key factor
      of tumorigenesis, drug resistance and tumor recurrence. However, the relationship
      between autophagy and OS CSCs still remains unclear. METHODS: CD271+ OS CSCs and
      CD271- OS cells were isolated by magnetic activated cell sorting. The autophagy
      level was evaluated by the mRNA expression of autophagy genes, the protein level
      of LC3II and p62, and the mean number of GFP-LC3 dot per cell. Lentivirus
      delivered specific shRNA was utilized to inhibit the corresponding gene
      expression. The cell viability was examined with CCK8 assay. The cell
      proliferation level was detected with BrdU staining assay. Cell death was
      determined by Annexin V/PI double staining of fluorescence activated cell
      sorting, lactate dehydrogenase release and caspase-3 activity. Tumorigenicity
      ability was evaluated by colony and sphere formation assay, the protein
      expression of stemness markers and tumor formation in nude mice. RESULTS: Our
      data indicated that CD271+ OS CSCs had a similar basic autophagy level with CD271
      OS cells. Autophagy deficiency had no observable effects on the levels of cell
      proliferation and death both in CD271+ and CD271- OS cells under normal
      condition. However, CD271+ OS cells showed a higher autophagy activity than CD271
      OS cells under hypoxia and low nutrient (LH) condition. Moreover, autophagy
      deficient CD271+ OS cells lost the advantage of tolerance to LH condition
      compared to CD271- OS cells. Meanwhile, autophagy deficiency enhanced the
      sensitivity to chemotherapeutics in the CD271+ cells to the comparable level in
      the CD271- cells. More importantly, deficient-autophagy decreased the protein
      expression of stemness markers and caused the disappearance of the superiority in
      tumorigenicity in vitro and vivo in CD271+ OS cells. CONCLUSION: The results
      above demonstrated that autophagy contributes to the stem-like features of CD271+
      OS CSCs. Inhibition of autophagy is a promising strategy in the CSCs-targeting OS
      therapy.

PMID- 27863493
TI  - Impact of low high-density lipoprotein-cholesterol level on 2-year clinical
      outcomes after acute myocardial infarction in patients with diabetes mellitus.
AB  - BACKGROUND: It is still unclear whether low high-density lipoprotein cholesterol
      (HDL-C) affects cardiovascular outcomes after acute myocardial infarction (AMI),
      especially in patients with diabetes mellitus. METHODS: A total of 984 AMI
      patients with diabetes mellitus from the DIabetic Acute Myocardial InfarctiON
      Disease (DIAMOND) Korean multicenter registry were divided into two groups based
      on HDL-C level on admission: normal HDL-C group (HDL-C >= 40 mg/dL, n = 519) and
      low HDL-C group (HDL-C < 40 mg/dL, n = 465). The primary endpoint was 2-year
      major adverse cardiovascular events (MACE), defined as a composite of cardiac
      death, non-fatal myocardial infarction (MI), and target vessel revascularization
      (TVR). RESULTS: The median follow-up duration was 730 days. The 2-year MACE rates
      were significantly higher in the low HDL-C group than in the normal HDL-C group
      (MACE, 7.44% vs. 3.49%, p = 0.006; cardiac death, 3.72% vs. 0.97%, p = 0.004; non
      fatal MI, 1.75% vs. 1.55%, p = 0.806; TVR, 3.50% vs. 0.97%, p = 0.007). Kaplan
      Meier analysis revealed that the low HDL-C group had a significantly higher
      incidence of MACE compared to the normal HDL-C group (log-rank p = 0.013). After
      adjusting for conventional risk factors, Cox proportional hazards analysis
      suggested that low HDL-C was an independent risk predictor for MACE (hazard ratio
      [HR] 3.075, 95% confidence interval [CI] 1.034-9.144, p = 0.043). CONCLUSIONS: In
      patients with diabetes mellitus, low HDL-C remained an independent risk predictor
      for MACE after adjusting for multiple risk factors during 2-year follow-up of
      AMI. TRIAL REGISTRATION: This study was the sub-analysis of the prospective multi
      center registry of DIAMOND (Diabetic acute myocardial infarction Disease) in
      Korea. This is the observational study supported by Bayer HealthCare, Korea.
      Study number is 15614. First patient first visit was 02 April 2010 and last
      patient last visit was 09 December 2013.

PMID- 27863494
TI  - Molecular epidemiology of hydropericardium syndrome outbreak-associated serotype
      4 fowl adenovirus isolates in central China.
AB  - In several parts of China, there have been a large number of hydropericardium
      syndrome (HPS) outbreaks caused by serotype 4 fowl adenovirus (FAdV-4) in broiler
      chickens since 2015. These outbreak-associated FAdV-4 strains were distinct from
      previous circulating strains which did not lead to severe HPS outbreaks. To
      better understand the molecular epidemiology of the currently circulating FAdV
      strains for effective diagnosis and treatment of HPS, we isolated 12 HPS outbreak
      associated FAdV-4 strains from different regions in central China and
      investigated their molecular characteristics by performing phylogenetic analyses
      based on the hexon genes. Our results indicated the FAdV-4 strains in this study
      all belonged to serotype FAdV-4, species FAdV-C. And in comparison with ON1, KR5,
      MX-SHP95, PK-01, PJ-06 strains within the cluster where outbreak-associated FAdV
      4 strains were located, the nucleotide sequence divergence were 1.31, 1.10, 1.42,
      2.77 and 2.84%, respectively. Phylogenetic analyses revealed the hexon genes of
      the 12 outbreak-associated strains clustered to a relatively independent branch
      of the tree, and evolved from the same ancestor and we suggested that these
      outbreak-associated FAdV-4 strains originate from earlier strains in India.

PMID- 27863495
TI  - Anaerobic poly-3-D-hydroxybutyrate production from xylose in recombinant
      Saccharomyces cerevisiae using a NADH-dependent acetoacetyl-CoA reductase.
AB  - BACKGROUND: Poly-3-D-hydroxybutyrate (PHB) that is a promising precursor for
      bioplastic with similar physical properties as polypropylene, is naturally
      produced by several bacterial species. The bacterial pathway is comprised of the
      three enzymes beta-ketothiolase, acetoacetyl-CoA reductase (AAR) and PHB
      synthase, which all together convert acetyl-CoA into PHB. Heterologous expression
      of the pathway genes from Cupriavidus necator has enabled PHB production in the
      yeast Saccharomyces cerevisiae from glucose as well as from xylose, after
      introduction of the fungal xylose utilization pathway from Scheffersomyces
      stipitis including xylose reductase (XR) and xylitol dehydrogenase (XDH). However
      PHB titers are still low. RESULTS: In this study the acetoacetyl-CoA reductase
      gene from C. necator (CnAAR), a NADPH-dependent enzyme, was replaced by the NADH
      dependent AAR gene from Allochromatium vinosum (AvAAR) in recombinant xylose
      utilizing S. cerevisiae and PHB production was compared. A. vinosum AAR was found
      to be active in S. cerevisiae and able to use both NADH and NADPH as cofactors.
      This resulted in improved PHB titers in S. cerevisiae when xylose was used as
      sole carbon source (5-fold in aerobic conditions and 8.4-fold under oxygen
      limited conditions) and PHB yields (4-fold in aerobic conditions and up to 5.6
      fold under oxygen limited conditions). Moreover, the best strain was able to
      accumulate up to 14% of PHB per cell dry weight under fully anaerobic conditions.
      CONCLUSIONS: This study reports a novel approach for boosting PHB accumulation in
      S. cerevisiae by replacement of the commonly used AAR from C. necator with the
      NADH-dependent alternative from A. vinosum. Additionally, to the best of our
      knowledge, it is the first demonstration of anaerobic PHB synthesis from xylose.

PMID- 27863496
TI  - Evaluation of anti-tumorigenic activity of BP3B against colon cancer with patient
      derived tumor xenograft model.
AB  - BACKGROUND: KIOM-CRC#BP3B (BP3B) is a novel herbal prescription that is composed
      of three plant extracts. Our preliminary study identified that BP3B exhibited
      potent anti-proliferative activity against various types of cancer cell lines in
      vitro. Because the in vivo anti-tumor effect of BP3B is not evaluated before
      clinical trial, we want to test it using patient's samples. METHODS: To confirm
      the in vivo anti-cancer effect of BP3B, we used genetically characterized patient
      derived colon tumor xenograft (PDTX) mouse model. Anti-cancer activity was
      evaluated with apoptosis, proliferation, angiogenesis and histological analysis.
      RESULTS: Oral administration of BP3B significantly inhibited the tumor growth in
      two PDTX models. Furthermore, TUNEL assay showed that BP3B induced apoptosis of
      tumor tissues, which was associated with degradation of PARP and Caspase 8 and
      activation of Caspase 3. We also observed that BP3B inhibited cancer cell
      proliferation by down-regulation of Cyclin D1 and induction of p27 proteins.
      Inhibition of angiogenesis in BP3B-treated group was observed with
      immunofluorescence staining using CD31 and Tie-2 antibodies. CONCLUSION: These
      findings indicated that BP3B has a strong growth-inhibitory activity against
      colon cancer in in vivo model and will be a good therapeutic candidate for
      treatment of refractory colon cancer.

PMID- 27863497
TI  - Next-generation sequencing facilitates detection of the classic E13-A20 EML4-ALK
      fusion in an ALK-FISH/IHC inconclusive biopsy of a stage IV lung cancer patient:
      a case report.
AB  - BACKGROUND: Inhibition of the oncogenic fusion-gene EML4-ALK is a current first
      line approach for patients with stage IV non-small cell lung cancer. While FISH
      was established as the gold standard for identifying these patients, there is
      accumulating evidence that other methods of detection, i.e., immunohistochemistry
      and next-generation sequencing (NGS), exist that may be equally successful.
      However, the concordance of these methods is under investigation. CASE
      PRESENTATION: Adding to the current literature, we here report a 56 year old
      female never-smoker with stage IV lung adenocarcinoma whose biopsy was IHC and
      FISH inconclusive but positive in NGS. Retroactive profiling of the resection
      specimen corroborated fusion reads obtained by NGS, FISH-positivity and showed
      weak ALK-positivity by IHC. Consequently, we diagnosed the case as ALK-positive
      rendering the patient eligible to crizotinib treatment. CONCLUSIONS: With IHC on
      biopsy material only, this case would have been overlooked withholding effective
      therapy.

PMID- 27863498
TI  - Factors affecting implementation of perinatal mental health screening in women of
      refugee background.
AB  - BACKGROUND: For women of refugee background, the increased risk of mental illness
      associated with pregnancy is compounded by pre- and post-settlement stressors. In
      Australia, antenatal screening for depression and anxiety symptoms using the
      Edinburgh Postnatal Depression Scale is recommended for all women. Despite this,
      screening is not routinely implemented and little is known about barriers and
      enablers to implementation for women of refugee background. METHODS: Semi
      structured interviews were conducted with a range of health professionals (n =
      28: midwives, obstetricians, perinatal mental health and refugee health experts,
      interpreters) and women of refugee background (n = 9). Themes generated from
      thematic analysis were examined in relation to the Theoretical Domains Framework
      and Cultural Competence Conceptual Framework, followed by identification of
      effective behaviour change techniques to address the barriers and enablers
      identified by participants. These techniques formed the basis of recommendations
      to inform sustainable implementation of screening and referral. RESULTS: Almost
      all participants perceived perinatal mental health screening to be necessary and
      most recognised the importance of post-traumatic stress disorder (PTSD)
      screening. Barriers and enablers were identified and related to eight domains:
      knowledge, skills, professional roles, beliefs about capabilities and
      consequences, environmental context, social influences and behavioural
      regulation. CONCLUSIONS: This research clarifies how mental health screening may
      be integrated into routine antenatal care for women of refugee background, in
      order to improve provision of recommended care. These theory-informed
      recommendations include an inter-disciplinary approach, coordinating care within
      and across services, addition of PTSD screening, and effective communication with
      women.

PMID- 27863499
TI  - What do health workers in Timor-Leste want, know and do? Findings from a national
      health labour market survey.
AB  - BACKGROUND: The objectives of this study were to understand the labour market
      dynamics among health workers, including their preferences and concerns, and to
      assess the skills, competence and performance (i.e. the 'know-do gap') of doctors
      working in Timor-Leste. METHODS: This cross-sectional survey was implemented in
      all 13 districts of Timor-Leste in 2014. We surveyed 443 health workers,
      including 175 doctors, 150 nurses and 118 midwives (about 20% of the health
      workers in the country). We also observed 632 clinical consultations with
      doctors, including 442 direct clinical observations, and tested 190 vignettes.
      RESULTS: The study highlights some positive findings, including the gender
      balance of health workers overall, the concentration of doctors in rural areas,
      the high overall reported satisfaction of staff with their work and high
      motivation, the positive intention to stay in the public sector, the feeling of
      being well prepared by training for work, the relatively frequent and
      satisfactory supervisions, and the good attitudes towards patients as identified
      in observations and vignettes. However, some areas require more investigations
      and investments. The overall clinical performance of the doctors was very good in
      terms of attitude and moderate in regard to history taking, health education and
      treatment. However, the average physical examination performance score was low.
      Doctors performed better with simulated cases than the real cases in general,
      which means they have better knowledge and skills than they actually
      demonstrated. The factors that were significantly associated with the clinical
      performance of doctors were location of the health facility (urban doctors were
      better) and consultation time (cases with more consultation time were better).
      Regression analysis suggests that lack of knowledge was significantly associated
      with lack of performance, while lack of motivation and equipment were not
      significant. CONCLUSIONS: The survey provides essential information for workforce
      planning and for developing training policies and terms and conditions that will
      attract and retain health workers in rural service. Improving the work
      environment and performance of doctors working in rural health facilities and
      ensuring compliance with clinical protocols are two priority areas needed to
      improve the performance of doctors in Timor-Leste.

PMID- 27863500
TI  - Simultaneous reconstruction of the bone and vessels for complex femoral defect.
AB  - BACKGROUND: Several methods have been reported for intercalary reconstruction of
      femoral defects. Of these, free vascularized fibula grafts (FVFG) are preferred
      because of their durability, bone-healing potential, and tolerance to infection.
      If the bone tumor invades the femoral vessels, simultaneous vascular
      reconstruction also becomes necessary and significant technical hurdles make limb
      salvage difficult. CASE PRESENTATION: We present a 10-year-old girl who underwent
      limb-sparing surgery for a distal femur osteosarcoma. The femoral defect was 15
      cm long, and the femoral vessel defect was 10 cm long. The femur was
      reconstructed with bilateral FVFG, and the femoral vessels were reconstructed
      with saphenous vein grafts. The grafts survived without vascular compromise, and
      the affected limb was preserved successfully. CONCLUSIONS: Combined use of
      bilateral FVFG and autologous vein grafts makes limb-sparing surgery for a large
      osteosarcoma of the femur possible.

PMID- 27863501
TI  - Mutations in LRRK2 impair NF-kappaB pathway in iPSC-derived neurons.
AB  - BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to both
      familial and idiopathic forms of Parkinson's disease (PD). Neuroinflammation is a
      key event in neurodegeneration and aging, and there is mounting evidence of LRRK2
      involvement in inflammatory pathways. In a previous study, we described an
      alteration of the inflammatory response in dermal fibroblasts from PD patients
      expressing the G2019S and R1441G mutations in LRRK2. METHODS: Taking advantage of
      cellular reprogramming, we generated induced pluripotent stem cell (iPSC) lines
      and neurons thereafter, harboring LRRK2G2019S and LRRK2R1441G mutations. We used
      gene silencing and functional reporter assays to characterize the effect of the
      mutations. We examined the temporal profile of TNFalpha-induced changes in
      proteins of the NF-kappaB pathway and optimized western blot analysis to capture
      alpha-synuclein dynamics. The effects of the mutations and interventions were
      analyzed by two-way ANOVA tests with respect to corresponding controls. RESULTS:
      LRRK2 silencing decreased alpha-synuclein protein levels in mutated neurons and
      modified NF-kappaB transcriptional targets, such as PTGS2 (COX-2) and TNFAIP3
      (A20). We next tested whether NF-kappaB and alpha-synuclein pathways converged
      and found that TNFalpha modulated alpha-synuclein levels, although we could not
      detect an effect of LRRK2 mutations, partly because of the individual
      variability. Nevertheless, we confirmed NF-kappaB dysregulation in mutated
      neurons, as shown by a protracted recovery of IkappaBalpha and a clear impairment
      in p65 nuclear translocation in the LRRK2 mutants. CONCLUSIONS: Altogether, our
      results show that LRRK2 mutations affect alpha-synuclein regulation and impair NF
      kappaB canonical signaling in iPSC-derived neurons. TNFalpha modulated alpha
      synuclein proteostasis but was not modified by the LRRK2 mutations in this
      paradigm. These results strengthen the link between LRRK2 and the innate immunity
      system underscoring the involvement of inflammatory pathways in the
      neurodegenerative process in PD.

PMID- 27863503
TI  - Lateral gene transfer in eukaryotes: tip of the iceberg or of the ice cube?
AB  - Lateral gene transfer (LGT) is the transmission of genes, sometimes across
      species barriers, outwith the classic vertical inheritance from parent to
      offspring. LGT is recognized as an important phenomenon that has shaped the
      genomes and biology of prokaryotes. Whether LGT in eukaryotes is important and
      widespread remains controversial. A study in BMC Biology concludes that LGT in
      eukaryotes is neither continuous nor prevalent and suggests a rule of thumb for
      judging when apparent LGT may reflect contamination.See research article:
      http://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0315-9 .

PMID- 27863502
TI  - Annexin A2 antibodies but not inhibitors of the annexin A2 heterotetramer impair
      productive HIV-1 infection of macrophages in vitro.
AB  - During sexual transmission of human immunodeficiency virus (HIV), macrophages are
      initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI)
      has been shown to protect against HIV infection of macrophages through
      interactions with annexin A2 (A2), which is found on the macrophage cell surface
      as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we
      investigated potential protein-protein interactions between A2 and HIV-1 gp120
      through a series of co-immunoprecipitation assays and a single molecule pulldown
      (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the
      interaction between A2 and S100A10 were tested for their ability to impair
      productive HIV-1 infection of macrophages. Our data suggest that interactions
      between HIV-1 gp120 and A2 exist, though this interaction may be indirect.
      Furthermore, an anti-A2 antibody impaired HIV-1 particle production in
      macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote
      HIV-1 infection of macrophages in its monomeric rather than tetrameric form.

PMID- 27863504
TI  - B-cell imaging with zirconium-89 labelled rituximab PET-CT at baseline is
      associated with therapeutic response 24 weeks after initiation of rituximab
      treatment in rheumatoid arthritis patients.
AB  - BACKGROUND: B cells are key players in the pathogenesis of rheumatoid arthritis
      (RA). Although successful in 50-60% of patients with RA, anti-B-cell therapy
      given as rituximab could be more efficient by identifying potential responders
      prior to treatment. Positron emission tomography (PET) using radiolabeled
      rituximab for B-cell imaging might provide the means to fulfil this unmet
      clinical need. The objective of this study was to investigate the association
      between biodistribution of zirconium-89 (89Zr)-rituximab on PET-computed
      tomography (CT) and clinical response in patients with RA. METHODS: We included
      20 patients with RA who were starting rituximab treatment. At the first
      intravenous (i.v.) therapeutic dose, patients were also injected with 89Zr
      rituximab, followed by PET-CT. European League Against Rheumatism (EULAR)
      response criteria were applied to determine response at week 24. PET-CT was
      analyzed visually and quantitatively. Lymph node (LN) biopsies were performed at
      0 and 4 weeks to correlate B-cell counts with imaging data. RESULTS: PET-positive
      hand joints (range 1-20) were observed in 18/20 patients. Responders had
      significantly higher 89Zr-rituximab uptake in PET-positive hand joints than non
      responders (median target-to-background (T/B)) ratios (IQR) were 6.2 (4.0-8.8)
      vs. 3.1 (2.2-3.9), p = 0.02). At T/B >=4.0, positive and negative predictive
      values for clinical response were respectively 90% and 75%. Quantitative 89Zr
      rituximab hand joint uptake on PET correlated inversely with CD22+ B-cell count
      in LN tissue at 4 weeks of treatment (r = 0.6, p = 0.05). In addition, the CD22+
      B-cell count in LN correlated positively with quantitative LN PET data at
      baseline, supporting the specificity of B-cell imaging on PET. CONCLUSIONS: Non
      invasive B-cell imaging by 89Zr-rituximab PET-CT has promising clinical value to
      select RA responders to rituximab at baseline. 89Zr-rituximab PET-CT may also
      hold promise for monitoring anti-B-cell therapies in other B-cell driven
      autoimmune diseases, such as systemic lupus erythematosus and Sjogren's disease.

PMID- 27863505
TI  - A genomic case study of desmoplastic small round cell tumor: comprehensive
      analysis reveals insights into potential therapeutic targets and development of a
      monitoring tool for a rare and aggressive disease.
AB  - BACKGROUND: Genome-wide profiling of rare tumors is crucial for improvement of
      diagnosis, treatment, and, consequently, achieving better outcomes. Desmoplastic
      small round cell tumor (DSRCT) is a rare type of sarcoma arising from mesenchymal
      cells of abdominal peritoneum that usually develops in male adolescents and young
      adults. A specific translocation, t(11;22)(p13;q12), resulting in EWS and WT1
      gene fusion is the only recurrent molecular hallmark and no other genetic factor
      has been associated to this aggressive tumor. Here, we present a comprehensive
      genomic profiling of one DSRCT affecting a 26-year-old male, who achieved an
      excellent outcome. METHODS: We investigated somatic and germline variants through
      whole-exome sequencing using a family based approach and, by array CGH, we
      explored the occurrence of genomic imbalances. Additionally, we performed mate
      paired whole-genome sequencing for defining the specific breakpoint of the EWS
      WT1 translocation, allowing us to develop a personalized tumor marker for
      monitoring the patient by liquid biopsy. RESULTS: We identified genetic variants
      leading to protein alterations including 12 somatic and 14 germline events (11
      germline compound heterozygous mutations and 3 rare homozygous polymorphisms)
      affecting genes predominantly involved in mesenchymal cell differentiation
      pathways. Regarding copy number alterations (CNA) few events were detected,
      mainly restricted to gains in chromosomes 5 and 18 and losses at 11p, 13q, and
      22q. The deletions at 11p and 22q indicated the presence of the classic
      translocation, t(11;22)(p13;q12). In addition, the mapping of the specific
      genomic breakpoint of the EWS-WT1 gene fusion allowed the design of a
      personalized biomarker for assessing circulating tumor DNA (ctDNA) in plasma
      during patient follow-up. This biomarker has been used in four post-treatment
      blood samples, 3 years after surgery, and no trace of EWS-WT1 gene fusion was
      detected, in accordance with imaging tests showing no evidence of disease and
      with the good general health status of the patient. CONCLUSIONS: Overall, our
      findings revealed genes with potential to be associated with risk assessment and
      tumorigenesis of this rare type of sarcoma. Additionally, we established a liquid
      biopsy approach for monitoring patient follow-up based on genomic information
      that can be similarly adopted for patients diagnosed with a rare tumor.

PMID- 27863506
TI  - Interleukin 37 limits monosodium urate crystal-induced innate immune responses in
      human and murine models of gout.
AB  - BACKGROUND: Interleukin (IL)-37 has emerged as a fundamental inhibitor of innate
      immunity. Acute gout is a self-limiting inflammatory response to monosodium urate
      (MSU) crystals. In the current study, we assessed the preventive and therapeutic
      effect of recombinant human IL-37 (rhIL-37) in human and murine gout models.
      METHODS: We investigated the expression of IL-37 in patients with active and
      inactive gouty arthritis and assessed the effect of rhIL-37 in human and murine
      gout models: a human monocyte cell line (THP-1) and human synovial cells
      (containing macrophage-like and fibroblast-like synoviocytes) exposed to MSU
      crystals, a peritoneal murine model of gout and a murine gouty arthritis model.
      After inhibition of Mer receptor tyrosine kinase (Mertk), levels of IL-1beta, IL
      8 and chemokine (C-C motif) ligand 2 (CCL-2) were detected by ELISA and
      expression of mammalian homologs of the drosophila Mad gene 3 (Smad), suppressor
      of cytokine signaling 3 (SOCS3), NACHT-LRR-PYD-containing protein 3 (NLRP3), and
      IL-8R of THP-1 were assessed by qPCR and western blot to explore the molecular
      mechanisms. RESULTS: Our studies strongly indicated that rhIL-37 played a potent
      immunosuppressive role in the pathogenesis of experimental gout models both in
      vitro and in vivo, by downregulating proinflammatory cytokines and chemokines,
      markedly reducing neutrophil and monocyte recruitment, and mitigating
      pathological joint inflammation. In our studies, rhIL-37 suppressed MSU-induced
      innate immune responses by enhancing expression of Smad3 and IL-1R8 to trigger
      multiple intracellular switches to block inflammation, including inhibition of
      NLRP3 and activation of SOCS3. Mertk signaling participated in rhIL-37 inhibitory
      pathways in gout models. By inhibition of Mertk, the anti-inflammatory effect of
      rhIL-37 was partly abrogated, and IL-1R8, Smad3 and SOCS3 expression were
      suppressed, whereas NLRP3 expression was reactivated. CONCLUSIONS: Our studies
      reveal that IL-37 limits runaway inflammation initiated by MSU crystal-induced
      immune responses, partly in a Mertk-dependent fashion. Thus, rhIL-37 has both
      preventive and therapeutic effects in gouty arthritis.

PMID- 27863507
TI  - Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound
      muscle phenotype.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      of upper and lower motor neurons. Mutations in the gene encoding the nuclear
      matrix protein Matrin 3 have been found in familial cases of ALS, as well as
      autosomal dominant distal myopathy with vocal cord and pharyngeal weakness. We
      previously found that spinal cord and muscle, organs involved in either ALS or
      distal myopathy, have relatively lower levels of Matrin 3 compared to the brain
      and other peripheral organs in the murine system. This suggests that these organs
      may be vulnerable to any changes in Matrin 3. In order to determine the role of
      Matrin 3 in these diseases, we created a transgenic mouse model for human wild
      type Matrin 3 using the mouse prion promoter (MoPrP) on a FVB background.We
      identified three founder transgenic lines that produced offspring in which mice
      developed either hindlimb paresis or paralysis with hindlimb and forelimb muscle
      atrophy. Muscles of affected mice showed a striking increase in nuclear Matrin 3,
      as well as the presence of rounded fibers, vacuoles, nuclear chains, and
      subsarcolemmal nuclei. Immunoblot analysis of the gastrocnemius muscle from
      phenotypic mice showed increased levels of Matrin 3 products migrating at
      approximately 120 (doublet), 90, 70, and 55 kDa. While there was no significant
      change in the levels of Matrin 3 in the spinal cord in the phenotypic mice, the
      ventral horn contained individual cells with cytoplasmic redistribution of Matrin
      3, as well as gliosis. The phenotypes of these mice indicate that dysregulation
      of Matrin 3 levels is deleterious to neuromuscular function.

PMID- 27863508
TI  - The effects of MCH insurance cards on improving equity in access and use of
      maternal and child health care services in Tanzania: a mixed methods analysis.
AB  - BACKGROUND: Inequity in access and use of child and maternal health services is
      impeding progress towards reduction of maternal mortality in low-income
      countries. To address low usage of maternal and newborn health care services as
      well as financial protection of families, some countries have adopted demand-side
      financing. In 2010, Tanzania introduced free health insurance cards to pregnant
      women and their families to influence access, use, and provision of health
      services. However, little is known about whether the use of the maternal and
      child health cards improved equity in access and use of maternal and child health
      care services. METHODS: A mixed methods approach was used in Rungwe district
      where maternal and child health insurance cards had been implemented. To assess
      equity, three categories of beneficiaries' education levels were used and were
      compared to that of women of reproductive age in the region from previous
      surveys. To explore factors influencing women's decisions on delivery site and
      use of the maternal and child health insurance card and attitudes towards the
      birth experience itself, a qualitative assessment was conducted at representative
      facilities at the district, ward, facility, and community level. A total of 31 in
      depth interviews were conducted on women who delivered during the previous year
      and other key informants. RESULTS: Women with low educational attainment were
      under-represented amongst those who reported having received the maternal and
      child health insurance card and used it for facility delivery. Qualitative
      findings revealed that problems during the current pregnancy served as both a
      motivator and a barrier for choosing a facility-based delivery. Decision about
      delivery site was also influenced by having experienced or witnessed problems
      during previous birth delivery and by other individual, financial, and health
      system factors, including fines levied on women who delivered at home.
      CONCLUSIONS: To improve equity in access to facility-based delivery care using
      strategies such as maternal and child health insurance cards is necessary to
      ensure beneficiaries and other stakeholders are well informed of the programme,
      as giving women insurance cards only does not guarantee facility-based delivery.

PMID- 27863509
TI  - Profibrotic mediators in tendon disease: a systematic review.
AB  - BACKGROUND: Tendon disease is characterized by the development of fibrosis.
      Transforming growth factor beta (TGF-beta), bone morphogenic proteins (BMPs) and
      connective tissue growth factor (CTGF) are key mediators in the pathogenesis of
      fibrotic disorders. The aim of this systematic review was to investigate the
      evidence for the expression of TGF-beta, BMPs and CTGF along tendon disease
      progression and the response of tendon cells to these growth factors accordingly.
      METHOD: We conducted a systematic screen of the scientific literature using the
      Medline database. The search terms used were "tendon AND TGF-beta," "tendon AND
      BMP" or "tendon AND CTGF." Studies of human samples, animal tendon injury and
      overuse models were included. RESULTS: Thirty-three studies were included. In
      eight studies the expression of TGF-beta, BMPs or CTGF was dysregulated in
      chronic tendinopathy and tendon tear patient tissues in comparison with healthy
      control tissues. The expression of TGF-beta, BMPs and CTGF was increased and
      showed temporal changes in expression in tendon tissues from animal injury or
      overuse models compared with the healthy control (23 studies), but the pattern of
      upregulation was inconsistent between growth factors and also the type of animal
      model. No study investigated the differences in the effect of TGF-beta, BMPs or
      CTGF treatment between patient-derived cells from healthy and diseased tendon
      tissues. Tendon cells derived from animal models of tendon injury showed
      increased expression of extracellular matrix protein genes and increased cell
      signaling response to TGF-beta and BMP treatments compared with the control cells
      (two studies). CONCLUSION: The expression of TGF-beta, BMPs and CTGF in tendon
      tissues is altered temporally during healing in animal models of tendon injury or
      overuse, but the transition during the development of human tendon disease is
      currently unknown. Findings from this systematic review suggest a potential and
      compelling role for TGF-beta, BMPs and CTGF in tendon disease; however, there is
      a paucity of studies analyzing their expression and stimulated cellular response
      in well-phenotyped human samples. Future work should investigate the dynamic
      expression of these fibrotic growth factors and their interaction with tendon
      cells using patient samples at different stages of human tendon disease.

PMID- 27863510
TI  - Establishing a reference array for the CS-alphabeta superfamily of defensive
      peptides.
AB  - BACKGROUND: "Invertebrate defensins" belong to the cysteine-stabilized alpha-beta
      (CS-alphabeta), also known as the scorpion toxin-like, superfamily. Some other
      peptides belonging to this superfamily of defensive peptides are
      indistinguishable from "defensins," but have been assigned other names, making it
      unclear what, if any, criteria must be met to qualify as an "invertebrate
      defensin." In addition, there are other groups of defensins in invertebrates and
      vertebrates that are considered to be evolutionarily unrelated to those in the CS
      alphabeta superfamily. This complicates analyses and discussions of this peptide
      group. This paper investigates the criteria for classifying a peptide as an
      invertebrate defensin, suggests a reference cysteine array that may be helpful in
      discussing peptides in this superfamily, and proposes that the superfamily
      (rather than the name "defensin") is the appropriate context for studying the
      evolution of invertebrate defensins with the CS-alphabeta fold. METHODS: CS
      alphabeta superfamily sequences were identified from previous literature and
      BLAST searches of public databases. Sequences were retrieved from databases, and
      the relevant motifs were identified and used to create a conceptual alignment to
      a ten-cysteine reference array. Amino acid sequences were aligned in MEGA6 with
      manual adjustments to ensure accurate alignment of cysteines. Phylogenetic
      analyses were performed in MEGA6 (maximum likelihood) and MrBayes (Bayesian).
      RESULTS: Across invertebrate taxa, the term "defensin" is not consistently
      applied based on number of cysteines, cysteine spacing pattern, spectrum of
      antimicrobial activity, or phylogenetic relationship. The analyses failed to
      reveal any criteria that unify "invertebrate defensins" and differentiate them
      from other defensive peptides in the CS-alphabeta superfamily. Sequences from
      various groups within the CS-alphabeta superfamily of defensive peptides can be
      described by a ten-cysteine reference array that aligns their defining structural
      motifs. CONCLUSIONS: The proposed ten-cysteine reference array can be used in
      addition to current nomenclature to compare sequences in the CS-alphabeta
      superfamily and clarify their features relative to one another. This will
      facilitate analysis and discussion of "invertebrate defensins" in an appropriate
      evolutionary context, rather than relying on nomenclature.

PMID- 27863511
TI  - Analysis of complement biomarkers in systemic sclerosis indicates a distinct
      pattern in scleroderma renal crisis.
AB  - BACKGROUND: The complement system has been implicated in pathogenesis of systemic
      sclerosis (SSc). The goal of the present study was to evaluate improved
      complement biomarkers in SSc. METHODS: The presence of C4d, reflecting activation
      of the classical/lectin pathways, C3bBbP corresponding to activation of the
      alternative pathway, and soluble terminal complement complexes (all complement
      pathways), was measured in plasma samples by enzyme-linked immunosorbent assay
      and correlated to clinical parameters. The study included 81 patients with
      limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched
      healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic
      arthritis and 20 with ankylosing spondylitis. Skin and kidney biopsies of
      selected patients were stained to detect deposited C3b as a marker of local
      complement activation. RESULTS: Biomarkers of activation of all complement
      pathways were increased in SSc compared with healthy controls and were similar to
      those in other rheumatic diseases. When patients with SSc were divided into
      subgroups, a distinct pattern of complement markers was observed in individuals
      with scleroderma renal crisis (SRC). By functional assay, we confirmed a
      significant decrease in complement haemolytic activity in SRC vs. non-SRC
      patients, indicating complement consumption. Further, we detected glomerular
      deposits of C3b in some patients with SRC. CONCLUSIONS: The data indicate that
      complement activation is an important feature of SRC.

PMID- 27863513
TI  - Epidemiology of rubella virus cases in the pre-vaccination era of Ethiopia, 2009
      2015.
AB  - BACKGROUND: Rubella is a common mild rash illness caused by rubella virus. The
      majority of infections occur in children and young adults. The infection is the
      cause of a serious birth defect known as Congenital Rubella Syndrome (CRS) when a
      woman acquires infection early in pregnancy. Ethiopia has not yet established
      rubella virus surveillance and has not yet introduced rubella vaccine into the
      routine immunization program. We characterize the epidemiology of laboratory
      confirmed rubella virus cases collected through measles surveillance from 2009 to
      2015 to better understand the burden of the disease in the country. METHODS: A
      descriptive analysis was made to characterize rubella cases reported through the
      national measles case based surveillance system. The measles case definition was
      used to capture potential rubella cases. A suspected measles case was a person
      with generalized rash and fever with cough, or coryza or conjunctivitis. Those
      cases whose sera were negative for measles IgM antibodies were tested for rubella
      IgM antibody. A confirmed rubella case was a person who tested positive for
      rubella IgM. Only laboratory confirmed rubella cases were analyzed in this
      article. RESULTS: Between 2009 and 2015, a total of 28,284 serum/plasma samples
      were collected and tested for measles IgM antibody and 11,151 (39.4%) were found
      positive. A total of 17,066 measles IgM negative or indeterminate samples were
      tested for rubella virus IgM and 2615 (15.3%) were found positive during the same
      period. Of 2615 confirmed rubella cases, 52.2% were females. The age of confirmed
      cases ranged from one month to 42 years with a mean age of 7.3 years. Three
      fourth of all confirmed rubella cases were aged less than 10 years. The number of
      laboratory confirmed rubella cases linearly increased from 83 in 2009 to 856 in
      2013 but dropped to 222 and 319 in 2014 and 2015 respectively. Higher number of
      cases occurred in the hot dry season (January through June) and in the central
      and western part of Ethiopia with 127 lab-confirmed outbreaks in the study
      period. CONCLUSIONS: Based on our analysis, rubella was found to be endemic
      throughout Ethiopia. Children below the age of 10 years were the most affected.
      The burden of rubella cases varied from year to year but had a seasonal peak in
      March. To better understand the magnitude of rubella prior to vaccine
      introduction, establishing rubella surveillance system, conducting sero
      prevalence studies among child bearing age females and establishing CRS sentinel
      surveillance among young infants are critical.

PMID- 27863512
TI  - Rheumatoid synovial fibroblasts differentiate into distinct subsets in the
      presence of cytokines and cartilage.
AB  - BACKGROUND: We investigated two distinct synovial fibroblast populations that
      were located preferentially in the lining or sub-lining layers and defined by
      their expression of either podoplanin (PDPN) or CD248, and explored their ability
      to undergo self-assembly and transmigration in vivo. METHODS: Synovial
      fibroblasts (SF) were cultured in vitro and phenotypic changes following
      stimulation with interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and
      transforming growth factor (TGF)-beta1 were examined. To examine the phenotype of
      SF in vivo, a severe combined immunodeficiency (SCID) human-mouse model of
      cartilage destruction was utilised. RESULTS: SF in the lining layer in rheumatoid
      arthritis (RA) expressed high levels of PDPN compared to the normal synovium,
      whereas CD248 expression was restricted to sub-lining layer cells. TNF-alpha or
      IL1 stimulation in vitro resulted in an increased expression of PDPN. In
      contrast, stimulation with TGF-beta1 induced CD248 expression. In the SCID human
      mouse model, rheumatoid SF recapitulated the expression of PDPN and CD248.
      Fibroblasts adjacent to cartilage expressed PDPN, and attached to, invaded, and
      degraded cartilage. PDPN+ CD248- SF preceded the appearance of PDPN- CD248+ cells
      in contralateral implants. CONCLUSIONS: We have identified two distinct SF
      populations identified by expression of either PDPN or CD248 which are located
      within different anatomical compartments of the inflamed synovial membrane. These
      markers discriminate between SF subsets with distinct biological properties. As
      PDPN-expressing cells are associated with early fibroblast migration and
      cartilage erosion in vivo, we propose that PDPN-expressing cells may be an
      attractive therapeutic target in RA.

PMID- 27863514
TI  - Statistical methods and modelling techniques for analysing hospital readmission
      of discharged psychiatric patients: a systematic literature review.
AB  - BACKGROUND: Psychiatric services have undergone profound changes over the last
      decades. CEPHOS-LINK is an EU-funded study project with the aim to compare
      readmission of patients discharged with psychiatric diagnoses using a registry
      based observational record linkage study design and to analyse differences in the
      findings for five different countries. A range of different approaches is
      available for analysis of the available data. Although there are some studies
      that compare selected methods for evaluating questions on readmission, there are
      to our knowledge no published systematic literature reviews on commonly used
      methods and their comparison. This work shall therefore provide an overview of
      the methods in use, their evolution throughout history and new developments which
      can further improve the research quality in this area. METHODS: Based on
      systematic literature reviews realized in the course of the CEPHOS-LINK study,
      this work is a systematic evaluation of mathematical (statistical and modelling)
      methods used in studies examining psychiatric readmission. The starting point
      were 502 papers, of which 407 were analysed in detail; Methods used were assigned
      to one of five categories with subcategories and analysed accordingly. Our
      particular interest next to survival analysis and regression models is modelling
      and simulation. RESULTS: As population sizes and follow-up times in the included
      studies varied widely, a range of methods was applied. Studies with bigger sample
      sizes conducted survival and regression analysis more often than studies with
      fewer patients did. These latter relied more on classical statistical tests (e.g.
      t-tests and Student Newman Keuls). Statistical strategies were often
      insufficiently described, posing a major problem for the evaluation. Almost all
      cases failed to provide and explanation of the rationale behind using certain
      methods. CONCLUSION: There is a discernible trend from classical
      parametric/nonparametric tests in older studies towards regression and survival
      analyses in more recent ones. Modelling and simulation were under-represented
      despite their high usability, as has been identified in other health applications
      and comparable research areas.

PMID- 27863515
TI  - Feasibility trial of a scalable psychological intervention for women affected by
      urban adversity and gender-based violence in Nairobi.
AB  - BACKGROUND: Living in conditions of chronic adversity renders many women more
      vulnerable to experiencing gender-based violence (GBV). In addition to GBV's
      physical and social consequences, the psychological effects can be pervasive.
      Access to evidence-based psychological interventions that seek to support the
      mental health of women affected by such adversity is rare in low- and middle
      income countries. METHODS: The current study evaluates a brief evidence-informed
      psychological intervention developed by the World Health Organization for adults
      impacted by adversity (Problem Management Plus; PM+). A feasibility randomised
      control trial (RCT) was conducted to inform a fully powered trial. Community
      health workers delivered the intervention to 70 women residing in three peri
      urban settings in Nairobi, Kenya. Women, among whom 80% were survivors of GBV (N
      = 56), were randomised to receive five sessions of either PM+ (n = 35) by
      community health workers or enhanced treatment as usual (ETAU; n = 35). RESULTS:
      PM+ was not associated with any adverse events. Although the study was not
      powered to identify effects and accordingly did not identify effects on the
      primary outcome measure of general psychological distress, women survivors of
      adversity, including GBV, who received PM+ displayed greater reductions in
      posttraumatic stress disorder symptoms following treatment than those receiving
      ETAU. CONCLUSIONS: This feasibility study suggests that PM+ delivered by lay
      health workers is an acceptable and safe intervention to reach women experiencing
      common mental disorders and be inclusive for those affected by GBV and can be
      studied in a RCT in this setting. The study sets the stage for a fully powered,
      definitive controlled trial to assess this potentially effective intervention.
      TRIAL REGISTRATION: ACTRN12614001291673 , 10/12/2014, retrospectively registered
      during the recruitment phase.

PMID- 27863516
TI  - Residential neighbourhood greenspace is associated with reduced risk of incident
      diabetes in older people: a prospective cohort study.
AB  - BACKGROUND: Three cross sectional studies suggest that neighbourhood greenspace
      may protect against incident diabetes. This study uses data from a longitudinal
      study with a large sample size to investigate the association between greenspace
      and the occurrence of incident diabetes over time. METHODS: Data was from the
      European Prospective Investigation of Cancer Norfolk, UK, cohort, recruitment
      1993-2007 (N = 23,865). Neighbourhoods were defined as 800 m circular buffers
      around participants' home locations, according to their home postcode (zip code).
      Greenspace exposure was defined as the percentage of the home neighbourhood that
      was woodland, grassland, arable land, mountain, heath and bog, according to the
      UK Land Cover Map. Cox proportional hazards regression examined the association
      between neighbourhood greenspace exposure and incident diabetes. The population
      attributable fraction assessed the proportion of diabetes cases attributable to
      exposure to least green neighbourhoods. Mediation analysis assessed if physical
      activity explained associations between greenspace and diabetes. Interaction
      analysis was used to test for the modifying effect of rurality and socio-economic
      status on the relationship between greenspace and diabetes. Models were adjusted
      for known and hypothesised confounders. RESULTS: The mean age of participants was
      59 years at baseline and 55.1% were female. The mean follow-up time was 11.3
      years. Individuals living in the greenest neighbourhood quartile had a 19% lower
      relative hazard of developing diabetes (HR 0.81; 95% CI 0.67, 0.99; p = 0.035;
      linear trend p = 0.010). The hazard ratio remained similar (HR 0.81; 95% CI 0.65,
      0.99; p = 0.042) after adjusting for age, sex, BMI, whether a parent had been
      diagnosed with diabetes and socio-economic status at the individual and
      neighbourhood level. A HR of 0.97 was attributed to the pathway through physical
      activity in a fully adjusted model, although this was non-significant (95% CI
      0.88, 1.08; p = 0.603). The incidence of diabetes in the least green
      neighbourhoods (with 20% greenspace on average) would fall by 10.7% (95% CI 
      2.1%, 25.2%; p = 0.106) if they were as green as the average neighbourhood
      observed across the whole cohort (59% greenspace on average). There were no
      significant interactions between rurality or socio-economic status and level of
      greenspace. CONCLUSIONS: Greener home neighbourhoods may protect against risk of
      diabetes in older adults, although this study does not support a mediation role
      for physical activity. Causal mechanisms underlying the associations require
      further investigation.

PMID- 27863517
TI  - Retrospective observation on contribution and limitations of screening for breast
      cancer with mammography in Korea: detection rate of breast cancer and incidence
      rate of interval cancer of the breast.
AB  - BACKGROUND: The purpose of this study was to determine the benefits and
      limitations of screening for breast cancer using mammography. METHODS:
      Descriptive design with follow-up was used in the study. Data from breast cancer
      screening and health insurance claim data were used. The study population
      consisted of all participants in breast cancer screening from 2009 to 2014. Crude
      detection rate, positive predictive value and sensitivity and specificity of
      breast cancer screening and, incidence rate of interval cancer of the breast were
      calculated. RESULTS: The crude detection rate of breast cancer screening per
      100,000 participants increased from 126.3 in 2009 to 182.1 in 2014. The positive
      predictive value of breast cancer screening per 100,000 positives increased from
      741.2 in 2009 to 1,367.9 in 2014. The incidence rate of interval cancer of the
      breast per 100,000 negatives increased from 51.7 in 2009 to 76.3 in 2014. The
      sensitivities of screening for breast cancer were 74.6% in 2009 and 75.1% in 2014
      and the specificities were 83.1% in 2009 and 85.7% in 2014. CONCLUSIONS: To
      increase the detection rate of breast cancer by breast cancer screening using
      mammography, the participation rate should be higher and an environment where
      accurate mammography and reading can be performed and reinforcement of quality
      control are required. To reduce the incidence rate of interval cancer of the
      breast, it will be necessary to educate women after their 20s to perform self
      examination of the breast once a month regardless of participation in screening
      for breast cancer.

PMID- 27863518
TI  - Safety and efficacy of bridging to lung transplantation with antifibrotic drugs
      in idiopathic pulmonary fibrosis: a case series.
AB  - BACKGROUND: Following recent approval of pirfenidone and nintedanib for
      idiopathic pulmonary fibrosis (IPF), questions arise about the use of these
      antifibrotics in patients awaiting lung transplantation (LTx). METHODS: Safety
      and efficacy of antifibrotic drugs in IPF patients undergoing LTx were
      investigated in a single-centre retrospective cohort analysis. RESULTS: A total
      of nine patients, receiving antifibrotic therapy for 419 +/- 315 days until
      subsequent LTx, were included. No major side effects were noted. Significant
      weight loss occurred during antifibrotic treatment (p = 0.0062). FVC tended to
      stabilize after 12 weeks of treatment in most patients. A moderate decline in
      FVC, TLC and DLCO was noted during the whole pretransplant time period of
      antifibrotic therapy. Functional exercise capacity and lung allocation score
      remained unchanged. No post-operative thoracic wound healing problems, nor severe
      early anastomotic airway complications were attributable to prior antifibrotic
      treatment. None of the patients developed chronic lung allograft dysfunction
      after a median follow-up of 19.8 (11.2-26.5) months; and post-transplant survival
      was 100% after 1 year and 80% after 2 years. CONCLUSIONS: Antifibrotic drugs can
      probably be safely administered in IPF patients, possibly attenuating disease
      progression over time, while awaiting LTx.

PMID- 27863519
TI  - TET-dependent regulation of retrotransposable elements in mouse embryonic stem
      cells.
AB  - BACKGROUND: Ten-eleven translocation (TET) enzymes oxidise DNA methylation as
      part of an active demethylation pathway. Despite extensive research into the role
      of TETs in genome regulation, little is known about their effect on transposable
      elements (TEs), which make up nearly half of the mouse and human genomes.
      Epigenetic mechanisms controlling TEs have the potential to affect their mobility
      and to drive the co-adoption of TEs for the benefit of the host. RESULTS: We
      performed a detailed investigation of the role of TET enzymes in the regulation
      of TEs in mouse embryonic stem cells (ESCs). We find that TET1 and TET2 bind
      multiple TE classes that harbour a variety of epigenetic signatures indicative of
      different functional roles. TETs co-bind with pluripotency factors to enhancer
      like TEs that interact with highly expressed genes in ESCs whose expression is
      partly maintained by TET2-mediated DNA demethylation. TETs and 5
      hydroxymethylcytosine (5hmC) are also strongly enriched at the 5' UTR of full
      length, evolutionarily young LINE-1 elements, a pattern that is conserved in
      human ESCs. TETs drive LINE-1 demethylation, but surprisingly, LINE-1s are kept
      repressed through additional TET-dependent activities. We find that the SIN3A co
      repressive complex binds to LINE-1s, ensuring their repression in a TET1
      dependent manner. CONCLUSIONS: Our data implicate TET enzymes in the evolutionary
      dynamics of TEs, both in the context of exaptation processes and of
      retrotransposition control. The dual role of TET action on LINE-1s may reflect
      the evolutionary battle between TEs and the host.

PMID- 27863520
TI  - Modeling the effects of palm-house proximity on the theoretical risk of Chagas
      disease transmission in a rural locality of the Orinoco basin, Colombia.
AB  - BACKGROUND: Chagas disease is a major public health concern in Latin America and
      it is transmitted by insects of the subfamily Triatominae, including Rhodnius
      spp. Since palm trees are ubiquitous in Colombia and a habitat for Rhodnius spp.,
      the presence of palms near villages could increase contact rates between vectors
      and humans. Therefore, knowing whether a relationship exists between the
      proximity of palms to villages and the abundance and distribution of vectors
      therein, may be critical for Chagas disease prevention programs. Adapting a
      mathematical model for R. prolixus population dynamics in a small village, we
      model the implications of changing distances between palms and dwellings, to the
      risk of Chagas disease infection. METHODS: We implemented a mathematical model
      that reflects R. prolixus population dynamics in a small village located in the
      department of Casanare (Colombia) to study the role of palm-house proximity. We
      varied the distance between palms and houses by monitoring the network global
      efficiency metric. We constructed 1,000 hypothetical villages varying distances
      and each one was run 100 times. RESULTS: According to the model, as palm-house
      proximity increases, houses were more likely to be visited by triatomine bugs.
      The number of bugs per unit time increased progressively in a non-linear fashion
      with high variability. We stress the importance of village configuration on the
      model output. CONCLUSIONS: From a theoretical perspective, palm-house proximity
      may have a positive effect on the incidence of Chagas disease. The model predicts
      a 1% increase in new human cases per year when houses and palms are brought
      closer by 75%.

PMID- 27863521
TI  - Seroprevalence of bovine theileriosis in northern China.
AB  - BACKGROUND: Bovine theileriosis is a common disease transmitted by ticks, and can
      cause loss of beef and dairy cattle worldwide. Here, an indirect enzyme-linked
      immunosorbent assay (iELISA) based on Theileria luwenshuni surface protein (TlSP)
      was developed and used to carry out a seroepidemiological survey of bovine
      theileriosis in northern China. METHODS: We used the BugBuster Ni-NTA His*Bind
      Purification Kit to purify recombinant TlSP (rTlSP), which was subsequently
      analyzed by Western Blotting to evaluate cross-reactivity with other pathogen
      positive sera. The iELISA method based on rTlSP was successfully developed. Sera
      from 2005 blood samples were tested with the rTlSP-iELISA method, and blood
      smears from these samples were observed by microscopy. RESULTS: The specificity
      of iELISA was 98.9%, the sensitivity was 98.5%, and the cut-off was selected as
      24.6%. Western Blot analysis of rTlSP confirmed that there were cross-reactions
      with Theileria luwenshuni, Theileria uilenbergi, Theileria ovis, Theileria
      annulata, Theileria orientalis and Theileria sinensis. The epidemiological survey
      showed that the highest positive rate of bovine theileriosis was 98.3%, the
      lowest rate was 84.1%, and the average positive rate was 95.4% by iELISA. With
      microscopy, the highest positive rate was 38.9%, the lowest rate was 5.1%, and
      the relative average positive rate was 13.7%. CONCLUSIONS: An rTlSP-iELISA was
      developed to detect circulating antibodies against bovine Theileria in northern
      China. This is the first report on the seroprevalence of bovine theileriosis in
      northern China, and it also provides seroepidemiological data on bovine
      theileriosis in China.

PMID- 27863523
TI  - Oligoclonal expansion of TCR Vdelta T cells may be a potential immune biomarker
      for clinical outcome of acute myeloid leukemia.
AB  - BACKGROUND: Recent data have shown that gammadelta T cells can act as mediators
      for immune defense against tumors. Our previous study has demonstrated that
      persisting clonally expanded TRDV4 T cells might be relatively beneficial for the
      outcome of patients with T cell acute lymphoblastic leukemia after hematopoietic
      stem cell transplantation (HSCT). However, little is known about the distribution
      and clonality of the TRDV repertoire in T cell receptor (TCR) of gammadelta T
      cells and their effects on the clinical outcome of patients with acute myeloid
      leukemia (AML). The aim of this study was to assess whether the oligoclonal
      expansion of TCR Vdelta T cells could be used as an immune biomarker for AML
      outcome. FINDINGS: gammadelta T cells were sorted from the peripheral blood of 30
      patients with untreated AML and 12 healthy donors. The complementarity
      determining region 3 (CDR3) sizes of eight TCR Vdelta subfamily genes (TRDV1 to
      TRDV8) were analyzed in sorted gammadelta T cells using RT-PCR and GeneScan. The
      most frequently expressed TRDV subfamilies in the AML patients were TRDV8 (86.67
      %) and TRDV2 (83.33 %), and the frequencies for TRDV1, TRDV3, TRDV4, and TRDV6
      were significantly lower than those in healthy individuals. The most frequent
      clonally expanded TRDV subfamilies in the AML patients included TRDV8 (56.67 %)
      and TRDV4 (40 %). The clonal expansion frequencies of the TRDV2 and TRDV4 T cells
      were significantly higher than those in healthy individuals, whereas a
      significantly lower TRDV1 clonal expansion frequency was observed in those with
      AML. Moreover, the oligoclones of TRDV4 and TRDV8 were independent protective
      factors for complete remission. Furthermore, the oligoclonal expansion
      frequencies of TRDV5 and TRDV6 in patients with relapse were significantly higher
      than those in non-recurrent cases. CONCLUSIONS: To the best of our knowledge, we
      characterized for the first time a significant alteration in the distribution and
      clonality of the TRDV subfamily members in gammadelta T cells sorted from AML
      patients. Clonally expanded TRDV4 and TRDV8 T cells might contribute to the
      immune response directed against AML, while oligoclonal TRDV5 and TRDV6 might
      occur in patients who undergo relapse. While the function of such gammadelta T
      cell clones requires further investigation, TRDV gammadelta T cell clones might
      be potential immune biomarkers for AML outcome.

PMID- 27863522
TI  - Cardiometabolic health, prescribed antipsychotics and health-related quality of
      life in people with schizophrenia-spectrum disorders: a cross-sectional study.
AB  - BACKGROUND: People with schizophrenia-spectrum disorders (SSD) often have high
      levels of obesity and poor cardiometabolic health. Certain types of
      antipsychotics have been shown to contribute towards weight gain and there is
      some equivocal evidence that obesity is related to poor health-related quality of
      life (HRQoL) in people with SSD. It is also still uncertain if antipsychotic
      polypharmacy/higher doses of antipsychotics are linked with HRQoL and/or
      increased risk of obesity/Cardiovascular Disease (CVD). Therefore, this study
      aimed to examine potential relationships between prescribed antipsychotic
      medication regimens, cardiometabolic health risks and HRQoL in community-based
      Chinese people with SSD. METHOD: This cross-sectional study reports the results
      of baseline measurements of a random sample of patients in an ongoing controlled
      trial of physical health intervention for people with severe mental illness. Data
      from these randomly-selected participants (n = 82) were analysed to calculate 10
      year CVD relative-risk (using QRISK(r)2 score), estimate the prevalence of
      metabolic syndrome and contextualize patients' prescribed antipsychotics (types,
      combinations and Daily Defined Dose equivalent). Patients self-reported their
      HRQoL (SF12v2) and their obesity condition was assessed by waist-circumference
      and Body Mass Index (BMI). RESULTS: Two-thirds of patients had a BMI >=23 kg/m2,
      almost half were centrally obese and 29% met the criteria for metabolic syndrome.
      The individual relative-risk of CVD ranged from 0.62 to 15, and 13% had a
      moderate-to-high 10-year CVD risk score. Regression models showed that lower
      physical HRQoL was predicted by higher BMI and lower mental HRQoL. Higher Defined
      Daily Dose, clozapine, younger age and male gender were found to explain 40% of
      the variance in CVD relative risk. CONCLUSION: The findings indicate that
      cardiometabolic health risks in people with SSD may be more common than those
      reported in the general Hong Kong population. The results also provide further
      support for the need to consider antipsychotic polypharmacy and higher doses of
      antipsychotics as factors that may contribute towards cardiometabolic risk in
      Chinese patients with SSD. Clinicians in Hong Kong should consider using routine
      CVD risk screening, and be aware that younger male patients who are taking
      clozapine and prescribed higher Defined Daily Dose seem to have the highest
      relative-risk of CVD. TRIAL REGISTRATION: Clinicaltrials.gov NCT02453217 .
      Prospectively registered on 19th May 2015.

PMID- 27863524
TI  - Positive mental health in outpatients: comparison within diagnostic groups.
AB  - BACKGROUND: Positive mental health (PMH) supplements the definition of mental
      health which is not just the mere absence of mental illness. It encompasses an
      individual's social, emotional and psychological well-being. This cross-sectional
      study examines the PMH levels in a multi-ethnic outpatient population and the
      socio-demographic correlates of PMH across the various diagnostic groups. In
      addition comparisons with the general population were conducted. METHODS:
      Outpatients with schizophrenia spectrum, depressive or anxiety disorders seeking
      treatment at a tertiary psychiatric care hospital were included in the study
      sample. All respondents completed the PMH instrument. Independent t-tests and
      ANOVA with Bonferroni post-hoc tests were used to establish differences between
      the PMH levels and domains. RESULTS: Three hundred and sixty outpatients with a
      mean age of 39.2 years were included in the study. 52.5% were younger adults (21
      39 years). There were slightly more males (50.8%) and 56.1% of the sample was
      unemployed. PMH scores differed between the patient and general populations.
      There were significant associations of the PMH domains with socio-demographic
      variables such as age, ethnicity, gender and education status in the patient
      population. CONCLUSIONS: PMH can be viewed as a protective factor of mental
      illnesses. As such it is critical that mental health professionals examine the
      domains of PMH in individuals with mental illnesses. This will in turn allow them
      to develop coping strategies that can look into focusing on emotional,
      psychological and social well-being appropriately to allow these individuals to
      thrive.

PMID- 27863525
TI  - Sexual dysfunction among youth: an overlooked sexual health concern.
AB  - BACKGROUND: There is growing recognition that youth sexual health entails a broad
      range of physical, emotional and psychosocial responses to sexual interactions,
      yet little is known about sexual dysfunctions and well being in youth
      populations. This study explored sexual dysfunctions among youth and its
      associations with other domains of sexual health. Sexual dysfunctions were
      defined as: problems related to orgasm, pain during intercourse, lack of sexual
      desire or sexual pleasure. METHODS: Data were drawn from the 2010 French national
      sexual and reproductive health survey comprising a random sample of 2309
      respondents aged 15-24 years. The current analysis included 842 females and 642
      males who had sexual intercourse in the last 12 months. Chi square tests were
      used to test for differences in sexual dysfunctions by sex and explore
      associations with other domains of sexual health. RESULTS: Half of females (48%)
      reported at least one sexual dysfunction versus 23% of males. However, over half
      (57%) of youth reporting at least one dysfunction did not consider this to hinder
      their sexuality. Altogether, 31% of females cited at least one sexual dysfunction
      hindering their sexuality-more than three times the 9% of males. Sexual
      dysfunction was strongly and inversely related to sexual satisfaction for both
      males and females and additionally to a recent diagnosis of STI or unintended
      pregnancy for females. Sexual dysfunctions hindering sexuality were also
      correlated with a history of unintended pregnancy among males. CONCLUSION: While
      most youth in France enjoy a satisfying sexual life, sexual dysfunction is
      common, especially among females. Public health programs and clinicians should
      screen for and address sexual dysfunction, which substantially reduce youth
      sexual wellbeing.

PMID- 27863526
TI  - Assessment of ICount software, a precise and fast egg counting tool for the
      mosquito vector Aedes aegypti.
AB  - BACKGROUND: Widespread in the tropics, the mosquito Aedes aegypti is an important
      vector of many viruses, posing a significant threat to human health. Vector
      monitoring often requires fecundity estimation by counting eggs laid by female
      mosquitoes. Traditionally, manual data analyses have been used but this requires
      a lot of effort and is the methods are prone to errors. An easy tool to assess
      the number of eggs laid would facilitate experimentation and vector control
      operations. RESULTS: This study introduces a built-in software called ICount
      allowing automatic egg counting of the mosquito vector, Aedes aegypti. ICount egg
      estimation compared to manual counting is statistically equivalent, making the
      software effective for automatic and semi-automatic data analysis. This technique
      also allows rapid analysis compared to manual methods. Finally, the software has
      been used to assess p-cresol oviposition choices under laboratory conditions in
      order to test the system with different egg densities. CONCLUSIONS: ICount is a
      powerful tool for fast and precise egg count analysis, freeing experimenters from
      manual data processing. Software access is free and its user-friendly interface
      allows easy use by non-experts. Its efficiency has been tested in our laboratory
      with oviposition dual choices of Aedes aegypti females. The next step will be the
      development of a mobile application, based on the ICount platform, for vector
      monitoring surveys in the field.

PMID- 27863527
TI  - The role of social position and depressive symptoms in adolescence for life
      course trajectories of education and work: a cohort study.
AB  - BACKGROUND: While a vast amount of studies confirm the social reproduction of
      class and status from one generation to the next, less is known about the role of
      health in the child generation for these processes. Research has shown that
      particularly mental distress in adolescence is important for future life chances.
      This study aimed to examine the importance of parental socioeconomic position and
      depressive symptoms in youth for life-course trajectories of education and labour
      market attachment among men and women. METHODS: Based on four waves of
      questionnaire data from the Northern Swedish Cohort (n = 1,001), consisting of
      individuals born in 1965, three steps of gender-separate analyses were
      undertaken. First, the individual trajectories of education and labour market
      attachment from age 18 to 42 were mapped through sequence analysis. Second,
      cluster analysis was used to identify typical trajectories. Third, two indicators
      of parental socioeconomic position - occupational class and employment status -
      and depressive symptoms at age 16 were used in multinomial regression analyses to
      predict adult life-course trajectories. RESULTS: Four typical trajectories were
      identified for men, of which three were characterised by stable employment and
      various lengths of education, and the fourth reflected a more unstable situation.
      Among women, five trajectories emerged, characterised by more instability
      compared to men. Low parental occupational class and unemployment were
      significantly associated with a higher risk of ending up in less advantaged
      trajectories for men while, for women, this was only the case for occupational
      class. Youth levels of depressive symptoms did not significantly differ across
      the trajectories. CONCLUSIONS: This study found support for the intergenerational
      reproduction of social position, particularly when measured in terms of parental
      occupational class. Youth depressive symptoms did not show clear differences
      across types of trajectories, subsequently impeding such symptoms to trigger any
      selection processes. While this could be a consequence of the specific framework
      of the current study, it may also suggest that depressive symptoms in youth are
      not a root cause for the more complex processes through which how social position
      develops across life. The possible impact of welfare and labour market policies
      is discussed.

PMID- 27863529
TI  - The expression of SIRT1 in articular cartilage of patients with knee
      osteoarthritis and its correlation with disease severity.
AB  - BACKGROUND: The study aims to investigate the expression of SIRT1 in articular
      cartilage of patients with primary knee osteoarthritis (OA) and its relationship
      with disease severity. METHODS: Cartilage tissue samples were collected from 38
      knee OA patients and 9 normal healthy controls and then ascribed to normal, mild,
      moderate, and severe groups on the basis of the improved Mankin grading system.
      The expression of SIRT1 in articular cartilage was detected by
      immunohistochemistry and western blots. The expression of p53 and acetylated p53
      (Ac-p53) was also measured by western blots. RESULTS: The mutual comparisons of
      the SIRT1 expression levels in all groups have statistical significance except
      the one between the mild and moderate groups. Moreover, western blot results
      showed that the SIRT1 was decreased and p53/Ac-p53 were increased in the OA
      group. The average gray level of SIRT1 increases with the improving grade of the
      improved Mankin grading system scorers. CONCLUSIONS: The expression of SIRT1 in
      articular cartilage is negatively associated with severity of knee OA, indicating
      that SIRT1 may act as a monitoring indicator for determining development and
      progression of knee OA.

PMID- 27863528
TI  - Oligodendrocyte development in the embryonic tuberal hypothalamus and the
      influence of Ascl1.
AB  - BACKGROUND: Although the vast majority of cells in our brains are glia, we are
      only beginning to understand programs governing their development, especially
      within the embryonic hypothalamus. In mice, gliogenesis is a protracted process
      that begins during embryonic stages and continues into the early postnatal
      period, with glial progenitors first producing oligodendrocyte precursor cells,
      which then differentiate into pro-oligodendrocytes, pro-myelinating
      oligodendrocytes, and finally, mature myelinating oligodendrocytes. The exact
      timing of the transition from neurogenesis to gliogenesis and the subsequent
      differentiation of glial lineages remains unknown for most of the Central Nervous
      System (CNS), and is especially true for the hypothalamus. METHODS: Here we used
      mouse embryonic brain samples to determine the onset of gliogenesis and expansion
      of glial populations in the tuberal hypothalamus using glial markers Sox9, Sox10,
      Olig2, PdgfRalpha, Aldh1L1, and MBP. We further employed Ascl1 and Neurog2 mutant
      mice to probe the influence of these proneual genes on developing embryonic
      gliogenic populations. RESULTS: Using marker analyses for glial precursors, we
      found that gliogenesis commences just prior to E13.5 in the tuberal hypothalamus,
      beginning with the detection of glioblast and oligodendrocyte precursor cell
      markers in a restricted domain adjacent to the third ventricle. Sox9+ and Olig2+
      glioblasts are also observed in the mantle region from E13.5 onwards, many of
      which are Ki67+ proliferating cells, and peaks at E17.5. Using Ascl1 and Neurog2
      mutant mice to investigate the influence of these bHLH transcription factors on
      the progression of gliogenesis in the tuberal hypothalamus, we found that the
      elimination of Ascl1 resulted in an increase in oligodendrocyte cells throughout
      the expansive period of oligodendrogenesis. CONCLUSION: Our results are the first
      to define the timing of gliogenesis in the tuberal hypothalamus and indicate that
      Ascl1 is required to repress oligodendrocyte differentiation within this brain
      region.

PMID- 27863530
TI  - Performances of low level hospital health caregivers after a neonatal
      resuscitation course.
AB  - BACKGROUND: High fidelity simulation has been executed to allow the evaluation of
      technical and non-technical skills of health caregivers. Our objective was to
      assess technical and non-technical performances of low level hospitals health
      caregivers who attended a Neonatal Resuscitation course using high fidelity
      simulation in a standard-setting scenario. METHODS: Twenty-three volunteers were
      asked to manage a simple scenario (infant with secondary apnea) after the course.
      Technical and non-technical skills were assessed by using previously published
      scores. Performances were assessed during the scenario and after 2 months by
      filmed video recordings. RESULTS: Sixteen (69.5%) participants failed to pass the
      minimum required technical score. Staff experience and participation in previous
      courses were associated to higher score in technical and non-technical skills,
      while working in level I or II hospitals did not affect the scores. Previous
      experience in neonatal resuscitation requiring positive pressure ventilation was
      associated to better non-technical performance. Technical and non-technical
      scores were significantly correlated (r = 0.67, p = 0.0005). Delayed and direct
      evaluation of technical skills provided the same scores. CONCLUSIONS: A neonatal
      resuscitation course, performed by using a high fidelity simulation manikin, had
      a limited impact on technical and non-technical skills of participants working in
      low level hospitals. Training programs should be tailored to the participants'
      professional background and to the more relevant sessions.

PMID- 27863531
TI  - Effects of continuous renal replacement therapy on linezolid
      pharmacokinetic/pharmacodynamics: a systematic review.
AB  - BACKGROUND: Major alterations in linezolid pharmacokinetic/pharmacodynamic
      (PK/PD) parameters might be expected in critically ill septic patients with acute
      kidney injury (AKI) who are undergoing continuous renal replacement therapy
      (CRRT). The present review is aimed at describing extracorporeal removal of
      linezolid and the main PK-PD parameter changes observed in critically ill septic
      patients with AKI, who are on CRRT. METHOD: Citations published on PubMed up to
      January 2016 were systematically reviewed according to the preferred reporting
      items for systematic reviews and meta-analyses (PRISMA) statement. All authors
      assessed the methodological quality of the studies and consensus was used to
      ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI
      treated with linezolid and on CRRT were considered eligible for the analysis only
      if operational settings of the CRRT machine, membrane type, linezolid blood
      concentrations and main PK-PD parameters were all clearly reported. RESULTS:
      Among 68 potentially relevant articles, only 9 were considered eligible for the
      analysis. Across these, 53 treatments were identified among the 49 patients
      included (46 treated with high-flux and 3 with high cut-off membranes).
      Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment
      performed amongst the studies. The extracorporeal clearance values of linezolid
      across the different modalities were 1.2-2.3 L/h for CVVH, 0.9-2.2 L/h for
      hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD
      parameters was reported. The optimal area under the curve/minimum inhibitory
      concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in
      one study only. CONCLUSIONS: Wide variability in linezolid PK/PD parameters has
      been observed across critically ill septic patients with AKI treated with CRRT.
      Particular attention should be paid to linezolid therapy in order to avoid
      antibiotic failure in these patients. Strategies to improve the effectiveness of
      this antimicrobial therapy (such as routine use of target drug monitoring,
      increased posology or extended infusion) should be carefully evaluated, both in
      clinical and research settings.

PMID- 27863534
TI  - Diagnosis a posteriori? Assessing gestational diabetes screening and management
      in Morocco.
AB  - BACKGROUND: In Morocco, gestational diabetes affects 1 in 10 pregnant women, but
      knowledge about screening and management practices outside university settings is
      limited. OBJECTIVE: To provide a comprehensive picture about the current
      situation of screening and management of gestational diabetes at different levels
      of care and to highlight existing challenges. DESIGN: We conducted a descriptive
      mixed methods study in the districts of Al Haouz and Marrakech by using both
      quantitative and qualitative methods, including document reviews of 369 antenatal
      cards and 299 hospital files, health facility inventories related to resource
      availability, 20 key informant interviews as well as focus group discussions with
      32 pregnant women and exit interviews with 122 antenatal care (ANC) clients.
      Quantitative data were descriptively analyzed using STATA Version 13, whereas
      qualitative data were thematically analyzed using NVIVO Version 10. RESULTS: The
      findings revealed that sensitization of women about gestational diabetes is low,
      and only 34.4% have ever heard about it before attending ANC. Fasting blood sugar
      is used for screening, and women are sent to external laboratories for testing. A
      fasting blood sugar of 0.92 g/l and above was documented in 12.3% of all
      antenatal cards examined. Women diagnosed with gestational diabetes are usually
      referred to a specialist despite general practitioners at health center level
      being responsible for the management of non-pregnant diabetic patients.
      CONCLUSIONS: Decentralization of screening for gestational diabetes and initial
      management of uncomplicated cases at the primary level of care could ease access
      to care and reduce the number of mothers who are diagnosed after a complication
      occurred.

PMID- 27863533
TI  - Ecological niche modelling of Rift Valley fever virus vectors in Baringo, Kenya.
AB  - BACKGROUND: Rift Valley fever (RVF) is a vector-borne zoonotic disease that has
      an impact on human health and animal productivity. Here, we explore the use of
      vector presence modelling to predict the distribution of RVF vector species under
      climate change scenario to demonstrate the potential for geographic spread of
      Rift Valley fever virus (RVFV). OBJECTIVES: To evaluate the effect of climate
      change on RVF vector distribution in Baringo County, Kenya, with an aim of
      developing a risk map for spatial prediction of RVF outbreaks. METHODOLOGY: The
      study used data on vector presence and ecological niche modelling (MaxEnt)
      algorithm to predict the effect of climatic change on habitat suitability and the
      spatial distribution of RVF vectors in Baringo County. Data on species occurrence
      were obtained from longitudinal sampling of adult mosquitoes and larvae in the
      study area. We used present (2000) and future (2050) Bioclim climate databases to
      model the vector distribution. RESULTS: Model results predicted potential
      suitable areas with high success rates for Culex quinquefasciatus, Culex
      univitattus, Mansonia africana, and Mansonia uniformis. Under the present
      climatic conditions, the lowlands were found to be highly suitable for all the
      species. Future climatic conditions indicate an increase in the spatial
      distribution of Cx. quinquefasciatus and M. africana. Model performance was
      statistically significant. CONCLUSION: Soil types, precipitation in the driest
      quarter, precipitation seasonality, and isothermality showed the highest
      predictive potential for the four species.

PMID- 27863532
TI  - Microvesicles secreted from equine amniotic-derived cells and their potential
      role in reducing inflammation in endometrial cells in an in-vitro model.
AB  - BACKGROUND: It is known that a paracrine mechanism exists between mesenchymal
      stem cells and target cells. This process may involve microvesicles (MVs) as an
      integral component of cell-to-cell communication. METHODS: In this context, this
      study aims to understand the efficacy of MVs in in-vitro endometrial stressed
      cells in view of potential healing in in-vivo studies. For this purpose, the
      presence and type of MVs secreted by amniotic mesenchymal stem cells (AMCs) were
      investigated and the response of endometrial cells to MVs was studied using a
      dose-response curve at different concentrations and times. Moreover, the ability
      of MVs to counteract the in vitro stress in endometrial cells induced by
      lipopolysaccharide was studied by measuring the rate of apoptosis and cell
      proliferation, the expression of some pro-inflammatory genes such as tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin 1beta (IL
      1beta), and metalloproteinases (MMP) 1 and 13, and the release of some pro- or
      anti-inflammatory cytokines. RESULTS: MVs secreted by the AMCs ranged in size
      from 100 to 200 nm. The incorporation of MVs was gradual over time and peaked at
      72 h. MVs reduced the apoptosis rate, increased cell proliferation values,
      downregulated pro-inflammatory gene expression, and decreased the secretion of
      pro-inflammatory cytokines. CONCLUSION: Our data suggest that some microRNAs
      could contribute to counteracting in-vivo inflammation of endometrial tissue.

PMID- 27863535
TI  - Towards an integrated primary and secondary HIV prevention continuum for the
      United States: a cyclical process model.
AB  - INTRODUCTION: Every new HIV infection is preventable and every HIV-related death
      is avoidable. As many jurisdictions around the world endeavour to end HIV as an
      epidemic, missed HIV prevention and treatment opportunities must be regarded as
      public health emergencies, and efforts to quickly fill gaps in service provision
      for all people living with and vulnerable to HIV infection must be prioritized.
      DISCUSSION: We present a novel, comprehensive, primary and secondary HIV
      prevention continuum model for the United States as a conceptual framework to
      identify key steps in reducing HIV incidence and improving health outcomes among
      those vulnerable to, as well as those living with, HIV infection. We further
      discuss potential approaches to address gaps in data required for programme
      planning, implementation and evaluation across the elements of the HIV prevention
      continuum. CONCLUSIONS: Our model conceptualizes opportunities to monitor and
      quantify primary HIV prevention efforts and, importantly, illustrates the
      interplay between an outcomes-oriented primary HIV prevention process and the HIV
      care continuum to move aggressively forward in reaching ambitious reductions in
      HIV incidence. To optimize the utility of this outcomes-oriented HIV prevention
      continuum, a key gap to be addressed includes the creation and increased
      coordination of data relevant to HIV prevention across sectors.

PMID- 27863536
TI  - How to support staff deploying on overseas humanitarian work: a qualitative
      analysis of responder views about the 2014/15 West African Ebola outbreak.
AB  - BACKGROUND: Responding to health crises overseas can be both rewarding and
      distressing for staff involved. OBJECTIVE: We interviewed UK staff involved in
      the 2014/15 Ebola response to identify experiences that positively or negatively
      affected them. METHOD: We conducted qualitative telephone interviews with 30
      Public Health England (PHE) staff and 21 non-governmental organisation (NGO)
      staff who had deployed to West Africa. RESULTS: The main motivations for
      deploying were for moral reasons and personal development. Families were largely
      supportive of deployment, although family tension was apparent. Pre-deployment
      training was largely viewed positively. Common stressors included dealing with
      death and suffering as well as concerns about contagion, while uplifting aspects
      included seeing patients improve and receiving thanks from community members.
      Communications with home were largely satisfactory, although participants
      commonly self-censored their communication. Inter-organisational tensions caused
      stress, particularly for PHE staff hosted by NGOs. After deployment, loss of
      motivation and being avoided by friends and family were common. CONCLUSION:
      Highlighting the personal benefits arising from deployments, as well as their
      moral value, may help to increase volunteering. Efforts to improve the support
      given to responders should focus on identifying how to better support families,
      preparing all staff members for dealing with death and the risk of contagion,
      providing opportunities for staff to more frequently experience the uplifting
      aspects of deployment, resolving inter-organisational difficulties, and educating
      others about the low risk posed by responders on their return.

PMID- 27863537
TI  - High-resolution proteomic and lipidomic analysis of exosomes and microvesicles
      from different cell sources.
AB  - Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are
      explored for use in diagnostics, therapeutics and drug delivery. However, little
      is known about the relationship of protein and lipid composition of EVs and their
      source cells. Here, we report high-resolution lipidomic and proteomic analyses of
      exosomes and MVs derived by differential ultracentrifugation from 3 different
      cell types: U87 glioblastoma cells, Huh7 hepatocellular carcinoma cells and human
      bone marrow-derived mesenchymal stem cells (MSCs). We identified 3,532 proteins
      and 1,961 lipid species in the screen. Exosomes differed from MVs in several
      different areas: (a) The protein patterns of exosomes were more likely different
      from their cells of origin than were the protein patterns of MVs; (b) The
      proteomes of U87 and Huh7 exosomes were similar to each other but different from
      the proteomes of MSC exosomes, whereas the lipidomes of Huh7 and MSC exosomes
      were similar to each other but different from the lipidomes of U87 exosomes; (c)
      exosomes exhibited proteins of extracellular matrix, heparin-binding, receptors,
      immune response and cell adhesion functions, whereas MVs were enriched in
      endoplasmic reticulum, proteasome and mitochondrial proteins. Exosomes and MVs
      also differed in their types of lipid contents. Enrichment in glycolipids and
      free fatty acids characterized exosomes, whereas enrichment in ceramides and
      sphingomyelins characterized MVs. Furthermore, Huh7 and MSC exosomes were
      specifically enriched in cardiolipins; U87 exosomes were enriched in
      sphingomyelins. This study comprehensively analyses the protein and lipid
      composition of exosomes, MVs and source cells in 3 different cell types.

PMID- 27863538
TI  - In vivo relevance of polymorphic Interleukin 8 promoter haplotype for the
      systemic immune response to LPS in Holstein-Friesian calves.
AB  - Interleukin 8, also known as CXC chemokine ligand 8 (CXCL8), is a critical
      chemokine in the recruitment of leukocytes to sites of infection and is a potent
      mediator of inflammation. We previously discovered 29 polymorphic sites in the
      promoter region of the bovine Interleukin 8 gene, which segregate into two
      distinct haplotypes, denoted IL8-h1 and IL8-h2. Population genetic analysis of
      these two haplotypes showed significant inter-breed differences in haplotype
      frequency, which is suggestive of selection acting at this locus. Furthermore
      functional characterisation identified that IL8-h2 was more active in mammary
      epithelial cells stimulated with the bacterial endotoxin, LPS. However, the in
      vivo relevance of these functional differences in the IL8 gene has not been
      ascertained. Therefore, in the current study, we tested the hypothesis that IL8
      haplotype would result in variation in the systemic immune response to LPS
      challenge in Holstein-Friesian (HF) calves. A Taqman assay was designed to
      genotype both Jersey and HF calves, from which 20 healthy HF calves (representing
      IL8-h1 and IL8-h2) from the same farm were subjected to LPS stimulation via
      jugular venepuncture (100ng/kg). Systemic immune profiling was subsequently
      performed up to 216h post-challenge. Haematological analysis showed perturbations
      in leukocyte populations of cells but only the lymphocyte response was
      significantly different between IL8-h1 and IL8-h2. IL8 expression levels were
      significantly different between haplogroups, at both the gene expression and
      protein levels (P<0.05). Circulating neutrophils were subsequently purified from
      each haplogroup to measure potential haplotype specific effects on neutrophil
      migration and bacterial killing but no significant differences were detected,
      which is likely due to the low circulating levels of IL8. We conclude that IL8
      haplotype significantly affects IL8 expression profile in response to bacterial
      endotoxin in vivo, and the significant increase in IL8 in IL8-h2 calves supports
      our earlier findings in vitro. Genetic variation at the IL8 locus therefore
      explains a proportion of the inter-breed and inter-individual variation in
      immunity between neonatal calves which is likely to influence their resistance to
      infection.

PMID- 27863539
TI  - Single nucleotide polymorphisms in major histocompatibility class II haplotypes
      are associated with potential resistance to inflammatory bowel disease in German
      shepherd dogs.
AB  - German shepherd dogs (GSD) in the UK are at increased risk of developing the
      Inflammatory Bowel Disaese (IBD). IBD is believed to be a multifactorial immune
      mediated disease affecting genetically predisposed dogs. The aim of the current
      study was to investigate whether susceptibility to IBD in GSD is associated with
      the major histocompatibility complex (MHC) class II locus (Dog Leukocyte Antigen,
      DLA). Sequence-based genotyping of the three polymorphic DLA genes DLA-DRB1, 
      DQA1 and -DQB1 was performed in 56 GSDs affected by IBD and in 50 breed-matched
      controls without any history of gastrointestinal signs. The haplotype DLA
      DRB1*015:02-DQA1*006:01-DQB1*023:01 was found to be present only in the control
      population and was associated with a reduced risk of IBD (P<0.001). In contrast,
      the haplotype DLA-DRB1*015:01-DQA1*006:01-DQB1*003:01 was associated with IBD
      (Odds ratio [OR]=1.93, confidence interval [CI]=1.02-3.67, P=0.05). This study
      has identified an association between DLA-type and canine IBD, supporting the
      immunogenetic aetiology and immunopathogenesis of this disease.

PMID- 27863540
TI  - Comparison of serum cytokine levels between dogs with multicentric lymphoma and
      healthy dogs.
AB  - In humans, multiple cytokines have been linked to the development of lymphoma,
      and are relevant biomarkers for response to chemotherapy and prognosis. In
      contrast, only a few circulating cytokines have been studied in dogs with
      lymphoma. We prospectively enrolled thirty-one dogs newly diagnosed with
      multicentric lymphoma. Immunophenotype was determined by flow cytometry in all
      dogs, separating them into 2 subgroups: B cell lymphoma (n=21) and T cell
      lymphoma (n=10). Nineteen healthy dogs were enrolled in the control group.
      Circulating cytokine concentrations were measured using a commercial canine
      multiplex magnetic bead-based assay which included Interleukin-2 (IL-2), IL-6, IL
      7, IL-8, IL-10, IL-15, IL-18, Granulocyte Macrophage Colony-Stimulating Factor
      (GM-CSF), Tumor Necrosis Factor-alpha (TNF-alpha), Interferon gamma (IFN-gamma),
      IFN-gamma induced Protein-10 (IP-10), Keratinocyte Chemoattractant-like (KC
      like), and Monocyte Chemoattractant Protein-1 (MCP-1). The serum levels of each
      cytokine were first compared between the lymphoma and control groups, and then
      between the B cell lymphoma, T cell lymphoma, and control groups. There was no
      significant difference between the lymphoma and healthy control groups regarding
      sex, age and weight. MCP-1, IL-6, and IL-10 were significantly higher in dogs
      with lymphoma compared to healthy dogs (p<0.01, p=0.01 and p=0.03, respectively).
      MCP-1 and IL-10 were significantly higher in the B cell lymphoma group than in
      the healthy group (p=0.01, p=0.01, respectively). MCP-1 and IL-6 levels were
      significantly higher in the T cell lymphoma group than in the healthy group
      (p=0.02, p<0.01, respectively). IL-6 was significantly higher in the T cell
      lymphoma group than in the B cell lymphoma group (p=0.03). Significant
      differences among the groups were found for IL-15 and KC-like, but they were
      affected by age and/or sex. There were no significant differences in serum IL-2,
      IL-7, IL-8, IL-18, GM-CSF, TNF-alpha, IFN-gamma, and IP-10 between any of the
      groups. Significant differences in red blood cell, white blood cell, neutrophil,
      lymphocyte and monocyte counts were also found between the different groups of
      dogs. Our data showed different serum cytokine and peripheral blood cell profiles
      between dogs with lymphoma and healthy dogs, and between dogs with B cell and T
      cell lymphoma. Further study is necessary to investigate the role of these
      cytokines in lymphoma pathogenesis, response to treatment, and prognosis, and the
      influence of age, sex and blood cell counts on their expression.

PMID- 27863541
TI  - Cellular endocytic compartment localization of expressed canine CD1 molecules.
AB  - CD1 molecules are glycoproteins present primarily on dendritic cells (DCs), which
      recognize and present a variety of foreign- and self-lipid antigens to T-cells.
      Humans have five different CD1 isoforms that survey distinct cellular
      compartments allowing for recognition of a large repertoire of lipids. The canine
      CD1 family consists of seven functional CD1 molecules (canine CD1a2, CD1a6,
      CD1a8, CD1a9, CD1b, CD1c and CD1e) and one presumed non-functional isoform
      (canine CD1d) due to a disrupted gene structure. The aim of this study was to
      describe in vitro steady-state localization ptterns of canine CD1 isoforms and
      their correlation with endocytic organelles. GFP-fused canine CD1 293T cell
      transfectants were stained with markers for early endocytic compartments (EEA-1)
      and late endocytic/lysosomal compartments (LAMP-1), respectively, and analyzed by
      confocal microscopy. Canine CD1a molecules localized to the plasma membrane and
      partially to the early endocytic compartment, but not to late endosomes or
      lysosomes. In contrast, canine CD1b was highly associated with late
      endosomal/lysosomal compartments and showed a predominant intracellular
      expression pattern. Canine CD1c protein expression localized more promiscuously
      to both the early endosomal compartments and the late endosomal/lysosomal
      compartments. The canine CD1e molecule showed a strictly intracellular expression
      with a partial overlap with late endosomal/lysosomal compartments. Lastly, canine
      CD1d was expressed abnormally showing only a diminished GFP expression. In
      conclusion, canine CD1 transfectants show distinct localization patterns that are
      similar to human CD1 proteins with the exception of the canine CD1d isoform,
      which most likely is non-functional. These findings imply that canine CD1
      localization overall resembles human CD1 trafficking patterns. This knowledge is
      important for the understanding of lipid antigen-receptor immunity in the dog.

PMID- 27863542
TI  - Optimisation and validation of a PCR for antigen receptor rearrangement (PARR)
      assay to detect clonality in canine lymphoid malignancies.
AB  - PCR for antigen receptor gene rearrangements (PARR) analysis is being
      increasingly used to assist diagnosis of canine lymphoma. In this study, PARR was
      carried out on consecutive samples received as part of routine diagnostic
      practice from 271 patients: 195 with lymphoid malignancies, 53 with reactive
      conditions and 23 with other neoplasms. Initially, published primer sets were
      used but later minor primer modifications were introduced and primers were
      rationalised to give a PARR panel that provides a good compromise between
      sensitivity and cost. Results were compared to diagnoses made by histology or
      cytology, coupled with immunophenotyping by flow cytometry or
      immunohistochemistry where possible. After exclusion of 11 poor quality samples,
      230/260 (88%) gave a clear result with 162/163 (99%) of samples classified as
      clonal and 56/67 (84%) classified as polyclonal giving results concordant with
      the cytological/histological diagnosis. Among 30 samples with equivocal results,
      21 had clonal peaks in a polyclonal background and nine showed little
      amplification. These were from patients with a range of neoplastic and non
      neoplastic conditions emphasising the need to interpret such results carefully in
      concert with other diagnostic tests. The combination of primer sets used in this
      study resulted in a robust, highly specific and sensitive assay for detecting
      clonality.

PMID- 27863543
TI  - Reduced humoral immunity and atypical cell-mediated immunity in response to
      vaccination in cows naturally infected with bovine leukemia virus.
AB  - Bovine leukemia virus (BLV) is a retrovirus that is widely distributed across US
      dairy herds: over 83% of herds are BLV-infected and within-herd infection rates
      can approach 50%. BLV infection reduces both animal longevity and milk production
      and can interfere with normal immune health. With such a high prevalence of BLV
      infection in dairy herds, it is essential to understand the circumstances by
      which BLV negatively affects the immune system of infected cattle. To address
      this question, BLV- and BLV+ adult, lactating Holstein dairy cows were vaccinated
      with Bovi-Shield GOLD(r) FP(r) 5 L5 HB and their immune response to vaccination
      was measured over the course of 28days. On day 0 prior to vaccination and days 7,
      14 and 28 post-vaccination, fresh PBMCs were characterized for T and B cell
      ratios in the periphery. Plasma was collected to measure titers of IgM, IgG1 and
      IgG2 produced against bovine herpesvirus 1 (BHV1), Leptospira hardjo and L.
      pomona, as well as to characterize neutralizing antibody titers produced against
      BHV1 and bovine viral diarrhea virus types 1 and 2. On day 18 post-vaccination,
      PBMCs were cultured in the presence of BHV1 and flow cytometry was used to
      determine IFNgamma production by CD4+, CD8+ and gammadelta T cells and to
      investigate CD25 and MHCII expression on B cells. BLV+ cows produced
      significantly lower titers of IgM against BHV1, L. hardjo and L. pomona and
      produced lower titers of IgG2 against BHV1. gammadelta T cells from BLV+ cows
      displayed a hyper reactive response to stimulation in vitro, although no
      differences were observed in CD4+ or CD8+ T cell activation. Finally, B cells
      from BLV+ cows exhibited higher CD25 expression and reduced MHCII expression in
      response to stimulation in vitro. All together, data from this study support the
      hypothesis that BLV+ cows fail to respond to vaccination as strongly as BLV- cows
      and, consequently, may have reduced protective immunity when compared to healthy
      BLV- cows.

PMID- 27863544
TI  - Effect of a post-weaning diet supplemented with functional feed additives on
      ileal transcriptome activity and serum cytokines in piglets challenged with
      lipopolysaccharide.
AB  - This study evaluated the potential of a weanling diet supplemented with trace
      minerals, vitamins, prebiotics, essential oils, antioxidants and bovine colostrum
      (BC) to modulate the inflammatory response of low-weight (LW) and high-weight
      (HW) piglets challenged with lipopolysaccharide (LPS). At weaning (20+/-1 d),
      litters from 32 sows were assigned to four groups: control diet (CTL), CTL plus
      dietary supplements (DS) or the antibiotic chlortetracycline (ATB), or DS plus BC
      in place of plasma proteins in the weanling diet (DS+BC). At 37 d (T0), two LW
      and two HW piglets were bled to evaluate ex vivo cytokine production by LPS
      activated peripheral blood mononuclear cells (PBMCs). In parallel, LW and HW
      piglets received intraperitoneal LPS and were bled at slaughter at 4h (T4) or 18h
      (T18) post-injection. Ileal tissues from these piglets and two unchallenged
      medium weight (MW) piglets per treatment were excised and analyzed by microarray.
      At T0, cytokine production of LPS-activated PBMCs was not affected by dietary
      treatments. At T4 after LPS challenge, serum concentrations of TNF-alpha, IL-6,
      IL-8, and IL-10 were increased in all piglets (P<0.01). Interestingly, the LW
      piglets had a higher TNF-alpha level than the HW piglets did (P=0.05). Dietary
      treatments had no effect on the piglet serum concentration of these cytokines
      neither at T4 nor at T18. Microarray data and QPCR analysis reveal that several
      genes were differentially expressed in the LPS-challenged piglets in comparison
      with the two control MW piglets (P<0.001). However, the dietary treatments had a
      slight effect on the ileal gene expression of the T4 and T18 LPS-challenged
      piglets when all piglets were included in the analysis. But when body weight (LW
      and HW) was considered as a fixed effect, the microarray analysis showed that the
      expression of 54 genes was differentially modulated by the dietary treatments in
      the T4 and T18 LPS-challenged LW piglets (P<0.05) while in HW piglets no
      difference was observed. QPCR analyses confirm that the level expression of
      several genes was reduced in LW piglets fed DS or DS+BC diet compared with ATB
      piglets. In conclusion, LPS challenge induced a transitional inflammation in
      weanling piglets that was characterized by increased blood-circulating cytokines
      and gut transcriptome activity. Results also suggest that the weanling diet
      supplemented with feed additives attenuated the ileal gene response to the LPS
      challenge, an effect that was more pronounced in the LW piglets.

PMID- 27863545
TI  - Porcine Treg depletion with a novel diphtheria toxin-based anti-human CCR4
      immunotoxin.
AB  - Regulatory T cells (Tregs) are known to play an important role in
      immunoregulation and have been shown to facilitate induction of transplantation
      tolerance. Chemokine (C-C motif) receptor 4 (CCR4) is expressed on the surface of
      effector Tregs involved in controlling alloimmune and autoimmune responses.
      Recently we have developed a novel diphtheria-toxin based anti-human CCR4
      immunotoxin for depleting CCR4+ cells in vivo. In this study, we have
      demonstrated that the anti-human CCR4 immunotoxin bound to porcine lymphocytes
      including CD4+FoxP3+ Tregs. Anti-human CCR4 immunotoxin effectively depleted
      CCR4+ Foxp3+ porcine Tregs in vivo. We observed depletion of up to 70-85% of the
      CCR4+Foxp3+ porcine Tregs in the peripheral blood and 85-91% in the lymph nodes
      following the anti-human CCR4 immunotoxin treatment in Massachusetts General
      Hospital (MGH) miniature swine. The depletion lasted for about one week with no
      significant reduction observed within CCR4- cell populations including CD8alpha+
      T cells, CCR4-CD4+ T cells and B cells. In summary, anti-human CCR4 immunotoxin
      effectively depleted CCR4+Foxp3+ porcine Tregs in both peripheral blood and lymph
      nodes.

PMID- 27863546
TI  - Identification of three novel B-cell epitopes of VMH protein from Vibrio mimicus
      by screening a phage display peptide library.
AB  - Vibrio mimicus is the causative agent of ascites disease in fish. The heat-labile
      hemolytic toxin designated VMH is an immunoprotective antigen of V. mimicus.
      However, its epitopes have not been well characterized. Here, a commercially
      available phage displayed 12-mer peptide library was used to screen epitopes of
      VMH protein using polyclonal rabbit anti-rVMH protein antibodies, and then five
      positive phage clones were identified by sandwich and competitive ELISA.
      Sequences analysis showed that the motif of DPTLL displayed on phage clone 15 and
      the consensus motif of SLDDDST displayed on the clone 4/11 corresponded to the
      residues 134-138 and 238-244 of VMH protein, respectively, and the synthetic
      motif peptides could also be recognized by anti-rVMH-HD antibody in peptide
      ELISA. Thus, both motifs DPTLL and SLDDDST were identified as minimal linear B
      cell epitopes of VMH protein. Although no similarity was found between VMH
      protein and the consensus motif of ADGLVPR displayed on the clone 2/6, the
      synthetic peptide ADGLVPR could absorb anti-rVMH-HD antibody and inhibit the
      antibody binding to rVMH protein in enhanced chemoluminescence Western blotting,
      whereas irrelevant control peptide did not affect the antibody binding with rVMH.
      These results revealed that the peptide ADGLVPR was a mimotope of VMH protein.
      Taken together, three novel B-cell epitopes of VMH protein were identified, which
      provide a foundation for developing epitope-based vaccine against V. mimicus
      infection in fish.

PMID- 27863547
TI  - Identification of histamine receptors in the canine gastrointestinal tract.
AB  - The important role of histamine in chronic gastrointestinal diseases has been
      increasingly recognized over the last two decades in human medicine. Histamine is
      released following mast cell activation and exerts its action through binding to
      four different histamine receptors (H1, H2, H3, and H4). Histamine receptors are
      dispersed throughout the body, and each different receptor mediates a unique
      response. Documentation of the presence and type of histamine receptors in the
      differing sections of the canine gastrointestinal tract will provide additional
      research opportunities to further explore the role of histamine and its receptors
      in chronic canine enteropathies, as well as potential therapeutic options. Full
      thickness gastric, duodenal, jejunal, ileal, and colonic biopsies were obtained
      from 6 clinically normal adult dogs immediately after humane euthanasia.
      Commercially available histamine receptor antibodies predicted to react with
      canine tissues were applied to paraffin-embedded tissue sections using standard
      immunohistochemistry techniques to identify different histamine receptors.
      Staining intensity was graded from negative to strong, and the specificity of
      each antibody was evaluated with western blot. The presence and distribution of
      histamine receptors varied by anatomic site and histologic level within sections
      of the canine gastrointestinal tract. All 4 histamine receptors were readily
      identified, although the distribution of H4 receptors was decreased in comparison
      to the other histamine receptors. The distribution of the various histamine
      receptors was similar to that seen in the normal human gastrointestinal tract. H1
      receptors were located in the stomach, lymphoid tissue of the ileum and colon,
      and the smooth muscle and ganglia of all sections. H2 receptors were located in
      all sections of the gastrointestinal tract, with greatest staining intensity in
      the gastric mucosa. H3 receptors were located in the stomach and colonic mucosa,
      smooth muscle and ganglia of all sections, and ileal and colonic lymphoid tissue.
      H4 receptors were located in the ganglia and smooth muscle of the
      gastrointestinal tract, as well as the gastric and colonic mucosal and ileal
      lymphoid tissue. Western blot demonstrated both specific and non-specific
      staining with the H1 and H3 receptor antibody, but good specificity with the H4
      receptor antibody. The H2 receptor antibody was not compatible with western blot
      techniques, despite excellent immunohistochemical specificity and consistency.
      Further studies to compare the density and distribution of the various histamine
      receptors in dogs with gastrointestinal disease are warranted.

PMID- 27863548
TI  - Impact of in vitro treatments of physiological levels of estradiol and
      progesterone observed in pregnancy on bovine monocyte-derived dendritic cell
      differentiation and maturation.
AB  - The specific factors which regulate differentiation and maturation of dendritic
      cells in bovine pregnancy remain unclear. We evaluated the influence of
      physiologically relevant in vitro treatments of progesterone (PG) and estradiol
      (E2) observed in late pregnancy on the differentiation and maturation of CD14+
      monocyte-derived dendritic cell (moDC) from non-pregnant, lactating dairy cows
      (n=7). We found that moDC differentiated in the presence of both E2 and PG had
      impaired E. coli-induced phenotypic maturation, specifically a significant
      reduction in CD80 and MHC II expression. Contrary to our previous work
      characterizing moDC from late gestating dairy cattle, we did not observe an
      increase in CD14 expression relative to the untreated control; this increase was
      only observed in the current data in the dexamethasone-treated moDC. The moDC
      treated with a combination of both E2 and PG had significantly greater
      upregulation of anti-inflammatory cytokine IL-10 relative to the untreated
      control, but TNFalpha production was not suppressed; only dexamethasone-treated
      moDC showed abrogated TNFalpha production. These data suggest moDC may be
      regulated by E2 and PG to hinder phenotypic maturation and regulate inflammatory
      responses. Pregnancy-associated hormone profiles appear to be involved in the
      generation of maternal immune tolerance in pregnancy. These hormone-facilitated
      changes to moDC in pregnancy may also impede optimal immune responses to both
      invading pathogens and routine vaccinations administered in late gestation
      through limited antigen presentation and increased anti-inflammatory cytokine
      production. These results provide insight into maternal immune modulation and
      elucidate potential immune changes necessary to facilitate bovine pregnancy.

PMID- 27863549
TI  - Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis
      measured using multiplex bead immunoassay analysis.
AB  - OBJECTIVE: To determine whether horses with clinically diagnosed Equine Recurrent
      Uveitis (ERU) and those with Leptospirosis infection have a specific cytokine
      profile in their aqueous humor (AH) and serum that differs from horses with
      uveitis secondary to other ocular inflammatory processes and from horses with
      normal eyes. ANIMALS STUDIED: Twenty-five client-owned horses with uveitis that
      were presented to the North Carolina State University Ophthalmology Service, and
      four University-owned horses without history or clinical signs of ocular disease.
      PROCEDURE: Samples of AH and serum were obtained from horses with ERU (n=13),
      acute or non-recurrent uveitis (UV; n=7), uveitis secondary to infectious
      keratitis (IK; n=5), and normal eyes (N; n=4). Cytokine levels in AH and serum
      were quantified using a multiplex bead immunoassay. Leptospiral antibody titers
      in serum and AH and PCR for Leptospiral DNA in AH were performed. RESULTS: In the
      AH of horses with ERU, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, FGF
      2, G-CSF, and RANTES were measured compared to UV, IK and N eyes, but the
      differences were not significant. However, IL-10 was significantly higher in ERU
      eyes compared to IK and N (P=0.029; 0.013), and IP-10 in ERU eyes was
      significantly higher than in UV and N (P=0.004). Furthermore, MCP-1 was
      significantly higher in ERU than N (P=0.04). In the serum, increased levels of IL
      1a, IL-4, IL-6, IL-8, IL-12p70, fractalkine, and G-CSF were measured in horses
      with ERU, but the levels were not significantly higher than those observed in UV,
      IK, or N horses. However, serum IP-10 levels in horses with ERU were
      significantly higher than in UV and N horses (P=0.005) and MCP-1 levels were
      significantly higher in ERU than N (P=0.03). Horses with marked ocular
      inflammation had significantly higher serum levels of G-CSF, IL-1a, fractalkine,
      IL-13, IL-4, IL-17a, IL-12p70, IFN-gamma, and MCP-1. Elevated IL-10 in AH was
      significantly associated with disease chronicity, both overall and in ERU eyes
      (P=0.049), and in horses with positive ocular leptospiral titers or leptospiral
      PCR, significant elevations of IL-10 (P=0.0018; 0.0032) and IP-10 (P=0.0342;
      0.043) were detected in the AH compared to leptospiral negative eyes.
      CONCLUSIONS: The anti-inflammatory cytokine IL-10 and the pro-inflammatory
      cytokine IP-10 appear to play an important role in ERU. Further studies are
      needed to further clarify and characterize cytokine profiles of specific ocular
      inflammatory diseases, but multiplex bead immunoassay technology shows promise as
      a diagnostically valuable tool.

PMID- 27863550
TI  - CC chemokine ligand 2 and CXC chemokine ligand 8 as neutrophil chemoattractant
      factors in canine idiopathic polyarthritis.
AB  - Canine idiopathic polyarthritis (IPA) is characterized by increased numbers of
      polymorphonuclear leukocytes (PMNs) in the synovial fluid (SF). In humans, CC
      chemokine ligand 2 (CCL2) and CXC chemokine ligand 8 (CXCL8) recruit monocytes
      and neutrophils, respectively, and are involved in various inflammatory
      disorders. The aim of this study was to assess the roles of these chemokines in
      driving PMNs infiltration into the joints of dogs with IPA. SF samples were
      collected from dogs with IPA (n=19) and healthy controls (n=8), and the
      concentrations of SF CCL2 and CXCL8 were determined by ELISA. Dogs with IPA had
      significantly higher concentrations of CCL2 (3316+/-2452pg/ml, mean+/-SD) and
      CXCL8 (3668+/-3879pg/ml) compared with the healthy controls (235+/-45pg/ml and
      <15.6pg/ml, respectively). Then, an in vitro chemotaxis assay was performed using
      a modified Boyden chamber (pore size: 3MUm). SF from IPA dogs had a
      chemoattractant activity for PMNs that purified from the peripheral blood of a
      healthy dog. We subsequently found that combination treatment with MK-0812 (an
      antagonist of CCL2 receptor) and repertaxin (an antagonist of CXCL8 receptors)
      significantly inhibited the migration of PMNs to SF from IPA dogs. Thus,
      expression of the CCL2 receptor (chemokine (CC motif) receptor 2 (CCR2)) was
      examined using polymerase chain reaction and immunocytochemistry. Canine
      peripheral blood PMNs exhibited significantly higher CCR2 mRNA expression levels
      than those in monocytes. In addition, we observed strong CCR2 expression on PMNs
      obtained from healthy controls and IPA dogs, although mononuclear cells did not
      express CCR2. Taken together, the data suggest that CCL2 acts as a canine PMNs
      chemotactic factor as well as CXCL8 and both CCL2 and CXCL8 facilitate the
      infiltration of PMNs into the joints of dogs with IPA.

PMID- 27863552
TI  - Generation of potent porcine monocyte-derived dendritic cells (MoDCs) by modified
      culture protocol.
AB  - In vitro derivation of dendritic cells (DCs) is an alternative approach to
      overcome the low frequency of primary DCs and the difficulty of isolation
      techniques for studying DC immunobiology. To date, the conventional culture
      protocol of porcine monocyte-derived DCs (MoDCs) has been widely used. However,
      this protocol is not practical due to the requirement of a substantial number of
      blood monocytes, and the process often interferes with DC maturation. To improve
      in vitro porcine MoDC generation, we modified the previous conventional DC
      generation protocol, based on the human and mouse primary DC culture system, and
      compared phenotypic and functional features of MoDCs derived from the modified
      protocol to the conventional protocol. The modified protocol consumed fewer
      monocytes but generated higher CD1+ cells with DC-like morphology and the ability
      of maturation. In addition, MoDCs from the modified protocol exhibited increased
      antigen uptake and IFN-gamma production in response to LPS stimulation. Our
      findings indicate that the modified protocol is expedient and reliable for
      generating potent MoDCs that substitute for primary DCs. This will be a valuable
      platform for future research in antigen delivery, vaccines and immunotherapy in
      pigs, as well as relevant veterinary species.

PMID- 27863551
TI  - In vitro cow uterine response to Escherichia coli, leukotrienes and cytokines.
AB  - The aim was to determine the dynamic profile of interactions between Escherichia
      coli (E. coli) and the actions of leukotrienes (LTs) and TNF and INFgamma
      (cytokines) in the uterus in vitro. Uterine explants (N=6) were incubated for 2,
      12 and 24h either as E. coli-treated (106CFU) or non-treated and/or with: LTB4
      and C4 (10-6M, for both LTs), LTs receptors antagonists (aLTR; 10-6M) and/or
      cytokines (each 10ng/ml). Toll Like Receptor 4 (TLR4) mRNA expression increased
      in explants incubated with E. coli, cytokines and LTs after 2 and 12h and aLTR
      inhibited the effect of LTs in explants incubated with E. coli (P<0.05). IL-6
      mRNA expression was up-regulated in E.coli-treated explants with cytokines after
      2h and cytokines with LTs after 12h (P<0.05). E. coli increased prostaglandin
      (PG)E2 output after all examined time points, and PGF2alpha and IL-6 levels in
      E.coli-treated explants after 12 and 24h with cytokines, with LTs (P<0.05). aLTR
      inhibited LT stimulating action on PGs and IL-6 output in explants incubated with
      E. coli after 12 and 24h (P<0.05). LTs modify and enhance experimentally induced
      infection: TLR4 and IL-6 mRNA expression, IL-6 and PGs secretion, and cytokines
      participate in this process.

PMID- 27863553
TI  - A comparison of serum and plasma cytokine values using a multiplexed assay in
      cats.
AB  - BACKGROUND: Degenerative joint disease (DJD) is highly prevalent in cats, and
      pain contributes to morbidity. In humans, alterations of cytokine concentrations
      have been associated with joint deterioration and pain. Similar changes have not
      been investigated in cats. Cytokine concentrations can be measured using
      multiplex technology with small samples of serum or plasma, however, serum and
      plasma are not interchangeable for most bioassays. Correlations for cytokine
      concentrations between serum and plasma have not been evaluated in cats.
      OBJECTIVE: To evaluate the levels of detection and agreement between serum and
      plasma samples in cats. ANIMALS: Paired serum and plasma samples obtained from 38
      cats. METHODS: Blood was collected into anti-coagulant free and EDTA
      Vacutainer(r) tubes, serum or plasma extracted, and samples frozen at -80 degrees
      C until testing. Duplicate samples were tested using a 19-plex feline
      cytokine/chemokine magnetic bead panel. RESULTS: Agreement between serum and
      plasma for many analytes was high, however correlation coefficients ranged from 
      0.01 to 0.97. Results from >50% of samples were below the lower limit of
      quantification for both serum and plasma for nine analytes, and for an additional
      three analytes for plasma only. CONCLUSIONS AND CLINICAL IMPORTANCE: While serum
      and plasma agreement was generally good, detection was improved using serum
      samples.

PMID- 27863554
TI  - Acute phase protein haptoglobin as inflammatory marker in serum and synovial
      fluid in an equine model of arthritis.
AB  - Acute phase proteins are useful inflammatory markers in horses. Haptoglobin (Hp)
      serum level is increased in horses undergoing different inflammatory processes,
      including arthritis. However, Hp concentration has not been assessed in
      inflammatory synovial fluid (SF). The aim of the present study was to investigate
      the Hp response in serum and SF in horses undergoing experimentally induced
      arthritis. For this purpose, serum and SF samples were collected from 12 animals
      before amphotericin B-induced arthritis was created (T0, healthy) and 15days
      after the lesion induction (T1, joint inflammation) and Hp was determined by
      single radial immunodiffusion. The Hp increase between T0 and T1 was significant
      in both serum and SF, and serum Hp concentration at T0 was significantly higher
      than in SF, but significant differences were not found at T1, indicating a higher
      Hp increase in SF. A significant positive correlation for Hp concentration
      between serum and SF samples was found. These results highlight the potential
      usefulness of Hp as inflammatory marker in horses, showing for the first time the
      increase of Hp in SF from joint inflammation in the horse.

PMID- 27863556
TI  - Oral vaccination of cattle with heat inactivated Mycobacterium bovis does not
      compromise bovine TB diagnostic tests.
AB  - In this study we investigated whether oral uptake of a heat inactivated M. bovis
      wildlife vaccine by domestic cattle induced systemic immune responses that
      compromised the use of tuberculin or defined antigens in diagnostic tests for
      bovine TB. Positive skin test and blood-based IFN-gamma release assay (IGRA)
      results were observed in all calves vaccinated via the parenteral route (i.e.
      intramuscular). In contrast, no positive responses to tuberculin or defined
      antigens were observed in either the skin test or IGRA test when performed in
      calves vaccinated via the oral route. In conclusion, our results suggest that the
      heat inactivated M. bovis vaccine could be used to vaccinate wildlife in a baited
      form in conjunction with the following in cattle: (i) continuation of existing
      tuberculin skin testing or novel skin test formats based on defined antigens; and
      (ii) the use of IGRA tests utilizing tuberculin or defined antigens.

PMID- 27863555
TI  - Test performance of three serological assays for the detection of Mycobacterium
      bovis infection in common warthogs (Phacochoerus africanus).
AB  - Sporadic cases of bovine tuberculosis (bTB) have been reported in warthogs in
      Southern Africa and confirmed through mycobacterial culture. However, there are
      no validated ante-mortem tests currently available for bTB in warthogs. In this
      study, we evaluated the use of three serological assays for the detection of
      Mycobacterium bovis infection in warthogs; an indirect enzyme-linked
      immunosorbent assay (ELISA) using bovine purified protein derivative (PPDb) as a
      capture antigen (indirect PPD ELISA), as well as two commercial assays, the TB
      ELISA-VK(r) and DPP(r) VetTB Assay. Test performance of these assays was compared
      using sera from 35 warthogs of known Mycobacterium bovis infection status. All
      three assays were able to distinguish M. bovis-infected from uninfected
      individuals with high sensitivity (Se) and specificity (Sp) (indirect PPD ELISA
      Se: 88%, Sp: 89%; TB ELISA-VK(r) 88%, 79%; DPP(r) VetTB Assay 75%, 89%,
      respectively). The assays performed very similarly and the ELISA assays showed
      the greatest agreement (kappa=0.89). These results indicate that M. bovis
      infected warthogs develop measurable pathogen-specific humoral responses which
      can be used to distinguish them from uninfected animals. Therefore, serological
      assays have value as ante-mortem bTB diagnostic tests in warthogs.

PMID- 27863557
TI  - In vitro assessment of the effects of temperature on phagocytosis, reactive
      oxygen species production and apoptosis in bovine polymorphonuclear cells.
AB  - Heat stress exerts a direct negative effect on farm animal health, triggering
      physiological responses. Environmental high temperature induces immunosuppression
      in dairy cows, increasing the risk of mastitis and milk somatic cell counts. The
      influence of heat stress on leukocytes activities has not been fully elucidated.
      The present in vitro study was aimed at assessing whether the exposure to
      temperature simulating conditions of severe whole body hyperthermia affects
      defensive functions of bovine blood polymorphonuclear cells. Blood was collected
      from seven clinically healthy, multiparous, late lactating Holstein cows. After
      isolation, PMN were incubated at either 39 or 41 degrees C. Phagocytosis,
      respiratory burst and apoptosis were then investigated. The selected temperatures
      of 39 degrees C or 41 degrees C mimicked conditions of normothermia or severe
      heat stress, respectively. Phagocytosis assay was carried out by measuring the
      fluorescence of phagocyted fluorescein-labelled E. coli bioparticles. The
      modulation of oxidative burst activity was studied by the cytochrome C reduction
      method. Apoptosis was determined by measuring the activities of two enzymes that
      play an effector role in the process, namely Caspase-3 and Caspase-7. Statistical
      analyses were performed using SPSS 22.0. A Student t-test for paired samples and
      a Generalised Estimating Equation were used based on data distribution. The
      phagocytosis rate was reduced (-37%, P<0.01) when PMN were incubated for 2h at 41
      degrees C, when compared to phagocytosis rate measured at 39 degrees C. The
      oxidative burst, as determined by extracellular production of reactive oxygen
      species (ROS), was also reduced by the exposure of cells to 41 degrees C compared
      to 39 degrees C. Such reduction ranged between -2 and -21% (P<0.05). Apoptosis
      rate was not affected by different temperatures. The results reported in this
      study suggest that phagocytosis and ROS production in PMN exposed to severe high
      temperature are impaired, partially explaining the higher occurrence of
      infections during periods of hot weather.

PMID- 27863558
TI  - Development of an autologous canine cancer vaccine system for resectable
      malignant tumors in dogs.
AB  - While conventional therapies exist for canine cancer, immunotherapies need to be
      further explored and applied to the canine setting. We have developed an
      autologous cancer vaccine (K9-ACV), which is available for all dogs with
      resectable disease. K9-ACV was evaluated for safety and immunogenicity for a
      variety of cancer types in a cohort of companion dogs under veterinary care. The
      autologous vaccine was prepared by enzymatic digestion of solid tumor biopsies.
      The resultant single cell suspensions were then UV-irradiated resulting in
      immunogenic cell death of the tumor cells. Following sterility and endotoxin
      testing, the tumor cells were admixed with CpG ODN adjuvant and shipped to the
      participating veterinary clinics. The treating veterinarians then vaccinated each
      patient with three intradermal injections (10 million cells per dose) at 30-day
      intervals (one prime and two boost injections). In a cohort of 20 dogs completing
      the study, 17 dogs (85%) developed an augmented IgG response to autologous tumor
      antigens as demonstrated using western blot analysis of pre- and post-peripheral
      blood samples. We also report several dogs have lived beyond expected survival
      time based on previously published data. In summary, K9-ACV is an additional
      option to be considered for the treatment of dogs with resectable cancer.

PMID- 27863559
TI  - Erratum to "Introduction" [Seminars in Diagnostic Pathology 33(5) (2016) 243].

PMID- 27863560
TI  - Signaling in the hypothalamus: New concepts.

PMID- 27863561
TI  - Precision Medicine and PET/Computed Tomography: Challenges and Implementation.
AB  - Precision Medicine is about selecting the right therapy for the right patient, at
      the right time, specific to the molecular targets expressed by disease or tumors,
      in the context of patient's environment and lifestyle. Some of the challenges for
      delivery of precision medicine in oncology include biomarkers for patient
      selection for enrichment-precision diagnostics, mapping out tumor heterogeneity
      that contributes to therapy failures, and early therapy assessment to identify
      resistance to therapies. PET/computed tomography offers solutions in these
      important areas of challenges and facilitates implementation of precision
      medicine.

PMID- 27863562
TI  - Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy
      Response Assessment in Oncology.
AB  - A variety of methods have been developed to assess tumor response to therapy.
      Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed
      tomography have been proposed to evaluate the treatment effectiveness in specific
      cancers and these allow more accurate therapy response assessment and survival
      prognostication. Multiple studies have addressed the utility of the volumetric
      PET biomarkers as prognostic indicators but there is no consensus about the
      preferred segmentation methodology for these metrics. Heterogeneous intratumoral
      uptake was proposed as a novel PET metric for therapy response assessment. PET
      imaging techniques will be used to study the biological behavior of cancers
      during therapy.

PMID- 27863563
TI  - Molecular Imaging and Precision Medicine in Dementia and Movement Disorders.
AB  - Precision medicine (PM) has been defined as "prevention and treatment strategies
      that take individual variability into account." Molecular imaging (MI) is an
      ideally suited tool for PM approaches to neurodegenerative dementia and movement
      disorders (MD). Here we review PM approaches and discuss how they may be applied
      to other associated neurodegenerative dementia and MD. With ongoing major
      therapeutic research initiatives that include the use of molecular imaging, we
      look forward to established interventions targeted to specific molecular
      pathophysiology and expect the potential benefit of MI PM approaches in
      neurodegenerative dementia and MD will only increase.

PMID- 27863564
TI  - Designing and Developing PET-Based Precision Model in Thyroid Carcinoma: The
      Potential Avenues for a Personalized Clinical Care.
AB  - This communication enumerates the current uses and potential areas where PET
      could be clinically utilized for developing "precision medicine" type model in
      thyroid carcinoma. (1) In routine clinics, PET imaging (with fluorodeoxyglucose
      [FDG]) is utilized to investigate patients of differentiated thyroid carcinoma
      (DTC) with high thyroglobulin and negative iodine scintigraphy (TENIS) and in
      medullary carcinoma thyroid (MCT) when the tumor markers (eg, calcitonin and
      carcino embryonic antigen [CEA]) are raised postoperatively (PET with FDG, 68Ga
      DOTA-NOC/TATE, FDOPA). Both are examples of management personalization, where PET
      computed tomography (CT) has been found substantially useful in detecting sites
      of metastatic disease and making decision with regard to feasibility and planning
      of surgery on an individual patient basis. (2) The next important area of
      management personalization is in patients of TENIS with metastatic disease not
      amenable to surgery through examining FDG-PET findings in tandem with radio
      iodine scan and 68Ga-DOTA-TATE/NOC PET/CT. Heterogeneous behavior of the
      metastatic lesions is frequently observed clinically: analyzing the findings of
      three studies aids in sub-segmenting patients into subgroups and thereby deciding
      upon the best approach (observation with LT4 suppression vs PRRT vs tyrosine
      kinase inhibitors) that could be individualized in a given case. (3) In
      metastatic/inoperable MCT, 68Ga-DOTA-TATE/NOC PET-CT helps in deciding upon
      feasibility of targeted PRRT in an individual patient and helps in follow-up and
      response evaluation. (4) Disease prognostification with FDG-PET is evolving both
      in DTC and MCT, where FDG avidity would indicate an aggressive biology, though
      the implication of this from treatment viewpoint is unclear at this point.
      Conversely, a negative FDG-PET in DTC and TENIS would suggest a favorable
      prognosis in an individual. (5) Iodine-124 PET/CT has the added potential of
      obtaining lesional dosimetry compared to the SPECT approach, and could help in
      selecting appropriate doses on an individual basis.

PMID- 27863565
TI  - Molecular Imaging and Precision Medicine in Breast Cancer.
AB  - Precision medicine, basing treatment approaches on patient traits and specific
      molecular features of disease processes, has an important role in the management
      of patients with breast cancer as targeted therapies continue to improve. PET
      imaging offers noninvasive information that is complementary to traditional
      tissue biomarkers, including information about tumor burden, tumor metabolism,
      receptor status, and proliferation. Several PET agents that image breast cancer
      receptors can visually demonstrate the extent and heterogeneity of receptor
      positive disease and help predict which tumors are likely to respond to targeted
      treatments. This review presents applications of PET imaging in the targeted
      treatment of breast cancer.

PMID- 27863566
TI  - Molecular Imaging and Precision Medicine in Lung Cancer.
AB  - Precision medicine allows tailoring of preventive or therapeutic interventions to
      avoid the expense and toxicity of futile treatment given to those who will not
      respond. Lung cancer is a heterogeneous disease functionally and morphologically.
      PET is a sensitive molecular imaging technique with a major role in the precision
      medicine algorithm of patients with lung cancer. It contributes to the precision
      medicine of lung neoplasia by interrogating tumor heterogeneity throughout the
      body. It provides anatomofunctional insight during diagnosis, staging, and
      restaging of the disease. It is a biomarker of tumoral heterogeneity that helps
      direct selection of the most appropriate treatment, the prediction of early
      response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in
      patients with lung cancer.

PMID- 27863567
TI  - Advancing Precision Nuclear Medicine and Molecular Imaging for Lymphoma.
AB  - PET with fluorodeoxyglucose F 18 (18F FDG-PET) is a meaningful biomarker for the
      detection, targeted biopsy, and treatment of lymphoma. This article reviews the
      evolution of 18F FDG-PET as a putative biomarker for lymphoma and addresses the
      current capabilities, challenges, and opportunities to enable precision medicine
      practices for lymphoma. Precision nuclear medicine is driven by new imaging
      technologies and methodologies to more accurately detect malignant disease.
      Although quantitative assessment of response is limited, such technologies will
      enable a more precise metabolic mapping with much higher definition image detail
      and thus may make it a robust and valid quantitative response assessment
      methodology.

PMID- 27863568
TI  - Molecular Imaging and Precision Medicine in Head and Neck Cancer.
AB  - The concept of using tumor genomic profiling information has revolutionized
      personalized cancer treatment. Head and neck (HN) cancer management is being
      influenced by recent discoveries of activating mutations in epidermal growth
      factor receptor and related targeted therapies with tyrosine kinase inhibitors,
      targeted therapies for Kristen Rat Sarcoma, and MET proto-oncogenes. Molecular
      imaging using PET plays an important role in assessing the biologic behavior of
      HN cancer with the goal of delivering individualized cancer treatment. This
      review summarizes recent genomic discoveries in HN cancer and their implications
      for functional PET imaging in assessing response to targeted therapies, and drug
      resistance mechanisms.

PMID- 27863569
TI  - Molecular Imaging and Precision Medicine in Prostate Cancer.
AB  - The aim of the present review is to discuss about the role of new probes for
      molecular imaging in the evaluation of prostate cancer (PCa). This review focuses
      particularly on the role of new promising radiotracers for the molecular imaging
      with PET/computed tomography in the detection of PCa recurrence. The role of
      these new imaging techniques to guide lesion-target therapies and the potential
      application of these molecular probes as theranostics agents is discussed.
      Finally, the molecular mechanisms underlying resistance to castration in PCa and
      the maintenance of active androgen receptor are discussed.

PMID- 27863570
TI  - Radionuclide Therapies in Molecular Imaging and Precision Medicine.
AB  - This article reviews recent advances and applications of radionuclide therapy.
      Individualized precision medicine, new treatments, and the evolving role of
      radionuclide therapy are discussed.

PMID- 27863571
TI  - Precision Medicine and PET/Computed Tomography: Time Has Arrived.

PMID- 27863572
TI  - Emergency Preparedness and the Development of Health Care Coalitions: A Dynamic
      Process.
AB  - Health care emergency preparedness has undergone significant changes since the
      first widespread distribution of federal funds occurred in 2002. Prior to the
      development of the Health Resources and Service Administration Bioterrorism
      Preparedness grant, support to hospitals and public health was limited to smaller
      regional preparedness programs such as the Chemical Stockpile Emergency
      Preparedness Program. Measurable progress with both the hospital preparedness
      program and public health emergency preparedness requires development of
      partnerships, establishment of coalitions, development of measurable objectives,
      and a community willingness to work together to solve complex preparedness
      problems.

PMID- 27863573
TI  - National Disaster Health Consortium: Competency-Based Training and a Report on
      the American Nurses Credentialing Center Disaster Certification Development.
AB  - As the largest profession of health care providers, nurses are an integral
      component of disaster response. Having clearly delineated competencies and
      developing training to acquire those competencies are needed to ensure nurses are
      ready when disasters occur. This article provides a review of nursing and
      interprofessional disaster competencies and development of a new
      interprofessional disaster certification. An overview of a standardized disaster
      training program, the National Disaster Health Consortium, is provided as an
      exemplar of a competency-based interprofessional disaster education program.

PMID- 27863574
TI  - All the Resources was Gone: The Environmental Context of Disaster Nursing.
AB  - US nurses are not prepared for the altered conditions of the disaster
      environment, nor has the context of providing disaster nursing care been a focus
      of disaster research. Using an existential phenomenologic approach, US nurses
      described the "not normal" conditions of the disaster environment they
      experienced as physically and emotionally challenging, because of the reduced
      infrastructural capabilities, unfamiliar patient populations, and reliance on low
      technology nursing with insufficient staff and supplies. Preparation for the
      reduced resources of the disaster environment should be integrated into current
      nursing education, clinical practice, and disaster preparedness policy.

PMID- 27863575
TI  - Complicated Realities: Mental Health and Moral Incongruence in
      Disaster/Humanitarian Response.
AB  - In the course of disaster/humanitarian response, providers are exposed to chaotic
      environments riddled with morally complex situations. This article disseminates
      research findings that highlight the impact of moral incongruence on responder
      mental health within the disaster/humanitarian setting by focusing on the theme
      "Everything was gray." The information is extracted from a larger, mixed methods
      study examining numerous variables considered within relevant literature to be
      influential in the occurrence of psychological distress among
      disaster/humanitarian responders.

PMID- 27863576
TI  - Federal Emergency Management Agency Response in Rural Appalachia: A Tale of
      Miscommunication, Unrealistic Expectations, and "Hurt, Hurt, Hurt".
AB  - In spring of 2012, rural southeastern Kentucky was impacted by torrential storms
      and flooding that activated federal disaster response through Federal Emergency
      Management Agency (FEMA). This qualitative research study examines the experience
      of community members affected by the Kentucky floods of 2012 (N=9) and describes
      their interactions with FEMA representatives, in their own voice, thereby giving
      insight into gaps in rural disaster response. The principal investigator spent 6
      weeks living in the community and conducted open-ended interviews. Narratives
      were transcribed verbatim and analyzed using a phenomenological approach.

PMID- 27863577
TI  - US Military Nurses: Serving Within the Chaos of Disaster.
AB  - The purpose of this article is to share US military nurses' experiences of
      responding to disasters. Using phenomenology, 23 participants serving as US
      military nurses from different service branches and the US Public Health Service
      volunteered for a single face-to-face interview. Five polar themes plus one final
      theme emerged from the narratives. Nurses expressed a sense of loss, reshaping of
      thoughts regarding disasters, and new appreciation of how people's lives are
      totally disrupted. Findings showed a need for change in nursing education,
      practice, training, policy, and recommendations for higher education and how the
      military may better educate its personnel.

PMID- 27863578
TI  - Wildfire Disasters and Nursing.
AB  - Multiple factors contribute to wildfires in California and other regions:
      drought, winds, climate change, and spreading urbanization. Little has been done
      to study the multiple roles of nurses related to wildfire disasters. Major
      nursing organizations support disaster education for nurses. It is essential for
      nurses to recognize their roles in each phase of the disaster cycle: mitigation,
      preparedness, response, and recovery. Skills learned in the US federal all
      hazards approach to disasters can then be adapted to more specific disasters,
      such as wildfires, and issues affecting health care. Nursing has an important
      role in each phase of the disaster cycle.

PMID- 27863579
TI  - Evolution of a Nursing Model for Identifying Client Needs in a Disaster Shelter:
      A Case Study with the American Red Cross.
AB  - From the time of Clara Barton, Red Cross nursing has had a key role in the care
      and support of persons affected by disasters in the United States. Hurricane
      Katrina and other events brought to light the need for a shelter model that was
      inclusive of the whole community, including persons with disabilities, at-risk
      and vulnerable populations, and children. From an intake process to a nursing
      model for assessment, an evidence-guided process informed a systematic approach
      for a registered nurse-led model of care.

PMID- 27863580
TI  - Hospital Decontamination: What Nurses Need to Know.
AB  - Incidents involving the release of hazardous materials challenge medical
      providers with safely, quickly, and correctly removing contaminants from the
      victim. While doing so, the safety of the first receiver, current patients,
      bystanders, as well as the victim all have to be considered. Key challenges with
      hospital decontamination include, but are not limited to, selection of team
      members, training protocols, employee turnover, and funding. Best practices,
      based on the available literature and evidence, include administration buy-in and
      support; strong policy and procedure documentation; equipment maintenance
      programs; and team member recruitment, retention, and education.

PMID- 27863581
TI  - Radiation, Fear, and Common Sense Adaptations in Patient Care.
AB  - Lack of understanding about the basic nature of radiation exposure and
      contamination may lead to unreasonable fear in nursing staff. A brief review of a
      well-known case shows that in general, both the public and health care providers
      are radiophobic. Studies have shown that the level of fear correlates inversely
      with an understanding of radiation. This article explores underlying principles
      of ionizing radiation and their application in patient management. Reality based,
      scientifically accurate information along with practical suggestions can free
      health care providers from unreasonable fear of victims of a radiation accident.

PMID- 27863582
TI  - Vehicle of Hope: Faith-based Disaster Response.
AB  - In August 2005, the United States experienced one of the most catastrophic and
      costly disasters in its history: Hurricane Katrina. Faith-based Organizations
      (FBOs) made a major contribution to the response and recovery efforts. Whereas
      the activities and skill sets of FBOs vary, their core missions are very similar:
      they want to provide hope. As a concept, hope has been purported to be essential
      for health and well-being, is viewed as multidimensional and a life force, as
      well as is highly individualized. This mixed methods study used interviews of the
      phenomenology tradition and the Herth Hope Index.

PMID- 27863583
TI  - Disaster Planning, Preparedness, Mitigation, Response, and Recovery: A Call for
      All Nurses to Action.

PMID- 27863584
TI  - Implications of Disaster Preparedness for Nursing.

PMID- 27863585
TI  - Transcending Our Boundaries.

PMID- 27863586
TI  - Jo Eland May Be Gone, but Her Legacy Remains.

PMID- 27863587
TI  - Corrigendum to "Maintaining canine sperm function and osmolyte content with
      multistep freezing protocol and different cryoprotective agents" [Cryobiol. 71
      (2015) 344-349].

PMID- 27863588
TI  - From the Editor's Perspective....

PMID- 27863589
TI  - Limb loss: The unspoken psychological aspect.
AB  - In the United States, health care providers have diagnosed 29.1 million people
      with diabetes. Uncontrolled diabetes is the main reason for limb loss. This
      review addresses the lack of psychological support after limb loss. Few scholarly
      sources analyze the psychological aspects of limb loss before and after
      amputation. These sources report that patients do not have a clear understanding
      of their disease process and that patients often report a lack of empathy and
      communication from health care providers. There is no standardization of
      postoperative care instructions causing great confusion and increasing anxiety
      for both the patient and the caregivers. Individuals with limb amputation express
      increased depression and body image disturbance along with social embarrassment
      after amputation. Postoperatively, patients report a decrease in resources once
      discharged home. Some studies suggest psychiatric consultation preamputation and
      postamputation. The literature also suggests increased communication between the
      patient undergoing amputation and their health care provider preoperatively and
      postoperatively.

PMID- 27863590
TI  - Quality of life of people with chronic ulcers.
AB  - INTRODUCTION: Patients with chronic ulcers have physical, social, and
      psychological changes that directly affect their quality of life. OBJECTIVES: To
      evaluate the quality of life and analyze the association between personal and
      health characteristics in patient quality of life for those with chronic ulcers.
      METHOD: A cross-sectional study, nonprobabilistic. The questionnaire to evaluate
      personal and health characteristics and the Ferrans and Power Quality of Life
      Index-Wound Version were used for the data collection. The sample consisted of
      200 patients with chronic ulcers of several etiologies (venous ulcers, pressure
      ulcers, diabetic ulcers, and mixed) recruited at the basic health units in two
      cities in the South of Minas Gerais, Brazil. RESULTS: Overall, the study found
      that their quality of life was rated as good. There was a positive correlation
      between the different ages (P = 0.0165), number of children (P = 0.0083), and
      practice of religion (P = 0.0394) with quality of life.

PMID- 27863591
TI  - Identifying beliefs about smoking in patients with peripheral vascular disease.
AB  - Peripheral vascular disease (PVD) is a chronic disabling illness that frequently
      results in the occlusion of arteries in lower limbs and may cause ischemia,
      gangrene, or infection. The single most significant factor contributing to both
      the onset and progression of PVD is smoking, which has addictive properties. Once
      smoking becomes a habitual behavior, combined with the atherosclerotic process, a
      disastrous pathway ensues. The aim of this project was to gain an understanding
      of the beliefs of patients with PVD who smoked. A nonexperimental, descriptive
      design was used. Data were obtained from a sample of participants with a known
      history of PVD who have had a previous vascular intervention and who are
      established patients in a vascular surgeon's private office N = 50. The majority
      of participants were male (n = 31; 63%) 65-74 years of age (n = 18; 36%), were
      unemployed (n = 30; 60%), and have smoked for greater than 51+ years (n = 13;
      26%). A scale that was developed guided by the behavioral beliefs subscale
      revealed that PVD patients enjoyed smoking, smoking helped them to relax, and
      they believed that they were addicted to smoking. Results from the normative
      beliefs subscale indicated that the spouse or significant other, children or
      those whom they lived with, did not approve of their smoking and also that their
      healthcare provider had discussed smoking cessation with them. The control
      beliefs subscale results demonstrated that most patients had attempted to quit
      smoking and believed that it would be a difficult behavior to stop and they would
      require the assistance of a patch or medication and feared the withdrawal
      symptoms. In conclusion, exploring the beliefs and thought process of patients
      who smoked provided a rich body of knowledge which can afford the healthcare
      professional with the ability to better understand the smoking experience as seen
      through the patients' eyes.

PMID- 27863592
TI  - Nursing interventions in stroke care delivery: An evidence-based clinical review.
AB  - INTRODUCTION: Generally, nursing interventions during the acute stages following
      a stroke aim at preventing secondary brain injury (intracranial hypertension),
      maintaining the airways (due to paralysis of the pharynx muscles), providing
      general body support (vital signs, fluid and electrolyte balance), and
      anticipating the occurrence of complications (atelectasis and pneumonia). AIM:
      This literature review is to prioritize nursing interventions for acute stroke
      and to update nursing roles and input considering recommended levels of evidence
      of care to date. METHOD AND MATERIALS: A systematic review was undertaken, and
      databases searched were Electronic Library Information Navigator (ELIN), Medline
      and the Cumulative Index to Nursing and Allied Health Literature from 1990 to
      2015, using the OVID interface. RESULTS: The search originally yielded 400
      articles of which 65 were selected for analysis and 12 of these included evidence
      synthesis (class I-IV, level A-Good Clinical Practice [GCP]). To facilitate early
      patient recovery, advanced nursing care should include the routine practice of a
      wide range of specific nursing interventions such as continence management,
      pressure area care, swallowing management, and early mobilization. Other
      important nursing interventions include the prevention of pulmonary
      thromboembolism and early antiplatelet therapy. CONCLUSIONS: For over 20 years,
      it has been established that specialized stroke care save lives, reduce
      disability, shorten length of stay, and generally have been associated with
      improved patient outcomes. Highly specialized nursing input is of paramount
      importance in achieving optimum patient outcomes and high quality of
      interdisciplinary care, providing a comprehensive, interactive, and holistic
      approach for both acute stroke and rehabilitation.

PMID- 27863593
TI  - Quality of life in elder adults one-year after coronary bypass.
AB  - BACKGROUND: Survival rates in the elderly after cardiac surgery have improved
      over the last decades and therewith more attention is directed toward Quality of
      Life (QoL) as a patient reported outcome measure. OBJECTIVE: The purpose of this
      study was to explore QoL in patients one year after coronary artery bypass
      grafting, with special interest in the elderly patients (>=80 years). METHODS: In
      a quantitative, retrospective single-center study patients with isolated coronary
      artery bypass grafting (eg, nonvalve) surgery aged 80 years or older and operated
      in 2013 were included (n = 32). A control group of patients aged younger than 80
      years was selected by matching based on gender and a recalculated (for age)
      logistic European System for Cardiac Operative Risk Evaluation (log EuroSCORE I)
      during the same period (n = 48). QoL assessment by the EuroQol questionnaire (EQ
      5D) and additional questions were performed at one-year follow-up. RESULTS: QoL
      in elderly patients was 0.79 versus 0.90 in younger patients (P = 0.013).
      Overall, 54.8% of the elderly experience some or extreme problems in mobility
      versus 18.8% in the younger group (P = 0.001). Elderly patients also experience
      more problems in self care (19.3 vs 4.2%, P = 0.029). Nine of the elderly (29%)
      valued their postoperative health status to be worse than preoperatively versus 5
      (10%) in the younger group (P = 0.028). Only patients aged 80 years or older
      would choose not to have surgery again (12.9%). Hospital mortality was 3.1% in
      the elderly group (n = 32) and 0% in the younger group (n = 48). CONCLUSION: Not
      all elderly patients experience benefits in terms of QoL one year after cardiac
      surgery. Therefore, potential benefits and risks need to be considered and
      discussed by physicians and patients before making the decision to operate or
      not.

PMID- 27863594
TI  - Research article review: Clinical comparison of automatic, noninvasive
      measurements of blood pressure in the forearm and upper arm.

PMID- 27863595
TI  - Utility of the hand-held continuous wave Doppler in the vascular examination: A
      review.

PMID- 27863596
TI  - Dermal Drug Delivery by Nanocarriers.

PMID- 27863597
TI  - Erratum.

PMID- 27863598
TI  - The effects of a simulated laughter programme on mood, cortisol levels, and
      health-related quality of life among haemodialysis patients.
AB  - OBJECTIVE: This study aimed to evaluate the effects of a simulated laughter
      programme on mood, cortisol levels, and health-related quality of life among
      haemodialysis patients. METHODS: Forty participants were randomly assigned to a
      laughter group (n = 20) or a control group (n = 20). Eleven participants
      completed the laughter programme after haemodialysis sessions and 18 control
      participants remained. The 4-week simulated laughter programme included weekly 60
      min group sessions of simulated laughter, breathing, stretching exercises, and
      meditation, as well as daily 15 s individual laughter sessions administered via
      telephone. Mood, cortisol levels, and health-related quality of life were
      analysed using the rank analysis of covariance, and Wilcoxon's signed rank test.
      RESULTS: The laughter group exhibited improvements in mood, symptoms, social
      interaction quality, and role limitations due to physical health. CONCLUSION: The
      simulated laughter programme may help improve mood and health-related quality of
      life among haemodialysis patients.

PMID- 27863599
TI  - Comparison between the effects of muscle relaxation and support groups on the
      anxiety of nursing students: A randomized controlled trial.
AB  - OBJECTIVE: To compare the effects of the two methods of muscle relaxation and
      support group on the anxiety levels of the nursing students. METHODS: In this
      randomized controlled trial, 150 nursing students who met the inclusion criteria
      were divided into three equal groups-muscle relaxation, support group, and
      control-using the permuted-block randomization method. The experimental groups
      received 5 sessions of intervention, while the control group did not receive any
      intervention at all. Using Spielberger's inventory, the researchers measured the
      anxiety levels of all three groups before and after the intervention. RESULTS:
      The results showed that both methods had a significant impact on anxiety levels
      of the nursing students; however, a comparison between their effects revealed
      that muscle relaxation had been more effective than support group. CONCLUSIONS:
      Considering the seriousness of the issue of anxiety for nursing students, it is
      important that measures be taken to reduce anxiety in this group.

PMID- 27863600
TI  - Herbal medicine for low sexual desire in menopausal women: A clinical review.
AB  - Many women typically experience a significant reduction in sexual desire during
      the late perimenopausal and early postmenopausal stages, with the biggest decline
      in sexual desire occurring from three years prior to two years after the final
      menstrual period. Despite being a prevalent female complaint, currently no
      standard treatment for low sexual desire exists. Herbal medicines have been used
      therapeutically all around the world, and are an important component of
      Traditional and Complementary Medicine. There have been numerous trials and
      pharmacological studies of specific herbal preparations related to the treatment
      of low sexual desire. This article serves to provide a clinical review of the
      evidence relating to the herbal treatment options for this common condition.

PMID- 27863601
TI  - Clinical efficacy of turmeric use in gingivitis: A comprehensive review.
AB  - INTRODUCTION: Gingivitis affects an estimated 80% of the population, and is
      characterized as the world's most predominant inflammatory periodontal disease.
      Without intervention, gingivitis can advance to alveolar bone loss. Therefore,
      the primary goal in patients suffering with gingivitis is to control plaque
      buildup and soft tissue inflammation. Current guidelines consider chlorhexidine
      as the gold standard in the prevention and treatment of gingivitis. However,
      negative side effects of chlorhexidine, including oral mucosal erosion,
      discoloration of teeth, and bitter taste, provide an opportunity for alternative
      medications. Turmeric, a commonly used herb, possesses anti-inflammatory,
      antioxidant, antibacterial, antiviral, and antifungal properties. By virtue of
      these properties, multiple controlled trials have been performed to investigate
      the efficacy of turmeric in gingivitis. OBJECTIVES: The aim of this comprehensive
      review is to summarize and evaluate the evidence on the efficacy of turmeric as
      compared to chlorhexidine in the prevention and treatment of gingivitis. RESULTS:
      PubMed, MedLine (Web of Science), and EBSCO (academic search complete) were
      utilized as primary literature search tools. The following search strategy was
      used: ((turmeric OR curcumin OR curcuma) AND (gingivitis OR "gum inflammation")).
      Five reviewed studies show that both turmeric and chlorhexidine significantly
      decrease plaque index (PI) and gingival index (GI), and can therefore be used in
      the prevention and treatment of gingivitis. CONCLUSIONS: Both chlorhexidine and
      turmeric can be used as an adjunct to mechanical means in preventing and treating
      gingivitis. However, trials longer than 21 days with a greater number of patients
      are necessary to further evaluate the comparison between turmeric and
      chlorhexidine.

PMID- 27863602
TI  - Effect of Fordyce Happiness Model on depression, stress, anxiety, and fatigue in
      patients with multiple sclerosis.
AB  - PURPOSE: This study was conducted to investigate the effect of Fordyce Happiness
      Model (FHM) on depression, stress, anxiety, and fatigue in MS patients. METHODS:
      In this clinical trial, 140 MS patients assigned to experimental and control
      groups. Depression, anxiety, stress, and fatigue were measured by Depression
      Anxiety Stress Scale-21 and Piper Standard Scale before and immediately and three
      months after the implementation of FHM. The data were analyzed by SPSS 18.
      RESULTS: Independent t-test indicated that total scores of stress, depression,
      and fatigue of the two groups were not significantly different before the
      intervention but were significantly different after the intervention (P?0.05).
      Moreover, anxiety scores of the two were not significantly different after the
      intervention (P?0.05). CONCLUSION: FHM can assist MS patients to manage their
      disease and associated problems in life. Besides that, since FHM is efficient and
      costless, it can be incorporated into the health interventions for MS patients.

PMID- 27863603
TI  - Effect of 'Exercise Without Movement' yoga method on mindfulness, anxiety and
      depression.
AB  - OBJECTIVE: To analyze the effect of the 'Exercise Without Movement' (E.W.M) yoga
      method on mindfulness and on the improvement of anxiety and depression symptoms.
      METHODS: A quasi-experimental study examined the effect of one month E.W.M.
      intervention among 38 participants who were enrolled voluntarily to both groups,
      study (n = 16) and control (n = 22). Five participants dropped out during the
      study. The State Mindfulness Scale (SMS) was used to measure mindfulness. The
      Anxiety Inventory Beck (BAI) and the Beck Depression Inventory (BDI-II) were used
      to measure the anxiety and depression symptoms, respectively, before and after
      the intervention. RESULTS: Study group showed both a statistically significant
      increase in mindfulness and decrease in anxiety and depression symptoms, compared
      with the control group. CONCLUSIONS: The E.W.M. has been useful in the
      development of mindfulness and in the treatment of anxiety and depression
      symptoms and may represent a new method in the mindfulness-based therapeutic
      application.

PMID- 27863604
TI  - Bowenwork for symptom management of women breast cancer survivors with
      lymphedema: A pilot study.
AB  - PURPOSE: The objectives of this pilot study for women breast cancer survivors
      with lymphedema was 1) to evaluate recruitment rates, retention rates, adherence
      to Bowenwork (a noninvasive complementary therapy involving gentle muscle
      movements), home exercises, safety and comfort; 2) determine the effect of
      Bowenwork on quality of life (QOL), functional status, perceived pain, range of
      motion (ROM), arm/ankle circumference (to assess for localized and systemic
      changes). METHODS: Participants received 4 Bowenwork sessions with home
      exercises. Initial and post assessments included QOL, functional status, and
      pain. ROM, arm/ankle circumference and pain measures were recorded before each
      session. RESULTS: Twenty-one women enrolled in the study; 95% completion;
      adherence 100%; home exercises 95%; no adverse events. The intervention improved
      mental health (SF-36-MCS); breast cancer-related functional (FACT-B); increased
      ROM; reduced arm circumferences. P value set at <0.05. CONCLUSIONS: The Bowenwork
      intervention was safe and acceptable for women breast cancer survivors with
      lymphedema.

PMID- 27863605
TI  - Perceptions of a hospital-based animal assisted intervention program: An
      exploratory study.
AB  - Research has shown that there are multiple benefits of animal assisted
      interventions for patients. However, the impact of interaction with these animals
      in staff is understudied, particularly in the acute care setting, and is thus a
      novel contribution to the literature on human-animal interaction. The purpose of
      this qualitative pilot study was to contribute to the body of knowledge
      surrounding the experiences and perceptions of hospital staff who have
      participated in a hospital-based animal assisted intervention program. Nine face
      to-face semi-structured interviews were conducted (4 staff nurses, 3 support
      staff members, and 2 hospital volunteers). Five themes emerged from the
      respondent interviews: (1) descriptions of the therapy dogs; (2) contacts with
      the dogs at work; (3) connection with the dogs outside of work; (4) benefits; (5)
      drawbacks. Our findings reflect abundantly positive hospital staff experiences.

PMID- 27863606
TI  - Use of complementary and alternative medicine in pregnancy and its impact on
      obstetric outcome.
AB  - OBJECTIVE: To evaluate the prevalence of use of complementary and alternative
      medicine (CAM) in a Malaysian antenatal population and its impact on obstetric
      outcome. DESIGN: Cross sectional study. SETTING: Obstetric Unit, Hospital
      Sultanah Bahiyah, Alor Setar, Kedah. MATERIAL AND METHOD: Women attending
      antenatal clinic and Patient Admission Centre (PAC) above 30 weeks gestation were
      given structured questionnaires to fill. Pregnancy outcome measures were
      documented and analyzed in relation to the information gathered through the
      questionnaire. SPSS Version 21 was used to analyze all data obtained. RESULTS:
      Out of 447 women, the overall prevalence of CAM usage in pregnancy was 85.2%. It
      was popular among pregnant mothers aged between 26 and 35 years old and most
      commonly used in the third trimester (p = 0.0.010) to facilitate labour. Other
      sociodemographic factors such as race, parity, education, occupation and
      residence were not significantly important. Traditional herbs was the commonest
      type of CAM used in pregnancy (58.3%) followed by selusuh (24.3%). About 78.5% of
      the CAM users delivered vaginally (p = 0.020) but a significant proportion
      (14.3%) had fetal distress (p = 0.035) compared to non CAM users. The most common
      type of herbs used was akar kayu bunga Fatimah (37.7%) and gamat (13.4%). In our
      study, usage of selusuh product and akar kayu bunga Fatimah had a significant
      impact in achieving vaginal delivery and shortened the duration of labour
      particularly in multiparae. The usage of Kacip Fatimah and Salindah was
      associated with preterm labour (p = 0.04)Tongkat Ali herbal coffee had a
      significant association with hypertensive disorders in pregnancy (p = 0.011) and
      fetal distress (p = 0.04) Meanwhile, the usage of Jamu Mustika Ratu was
      significantly associated with low birth weight in grandmultiparae (p = 0.026)and
      spirulina was significantly associated with oligohydramnios (p = 0.04).
      CONCLUSION: Usage of CAM in pregnancy in the Malaysian population is of high
      prevalence CAM in pregnancy has beneficial and adverse obstetric outcomes. More
      research is needed to establish the safety of usage of various forms of CAM in
      pregnancy.

PMID- 27863607
TI  - "Awareness is the first step": An interprofessional course on mindfulness &
      mindful-movement for healthcare professionals and students.
AB  - High levels of stress and related burnout in healthcare professionals (HCPs) are
      prevalent and costly conditions. Mindfulness training has received recent
      attention as a possible prevention/intervention strategy to enhance resilience to
      stress and reduce risk of burnout in HCPs. The purpose of this mixed-methods
      pilot study was to evaluate the preliminary feasibility, acceptability, and
      preliminary effects of an 8-week mindfulness curriculum for interprofessional
      HCPs and trainees (n = 27). Qualitative findings supported feasibility and
      acceptability of the course for a wide variety of HCP disciplines, including
      nursing, dentistry, medicine, pharmacy, social work, mental health, and clinical
      research. Despite being limited by a small sample size, there were statistically
      significant reductions in perceived stress, anxiety, and specific aspects of
      burnout from pre-to post-intervention and there was a trend in an enhanced sense
      of personal accomplishment over time.

PMID- 27863608
TI  - Is energy healing an effective non-pharmacological therapy for improving symptom
      management of chronic illnesses? A systematic review.
AB  - BACKGROUND: Emerging evidence suggests that some people living with non
      communicable diseases (NCDs) have integrated energy healing into their self
      management strategy, however little is known about its efficacy. PURPOSE: To
      identify energy healing interventions that impacted positively on the symptom
      management outcomes for patients living in the community with various NCDs.
      METHODS: A systematic review of energy healing interventions for the management
      of non-communicable disease related symptoms, conducted between 01 January 2000
      and 21 April 2015, published in an English peer-reviewed journal. This review
      conforms to the PRISMA statement. RESULTS: Twenty seven studies were identified
      that evaluated various energy healing interventions involving 3159 participants.
      Thirteen of the energy healing trials generated statistically significant
      outcomes. CONCLUSIONS: Energy healing has demonstrated some improvement in
      illness symptoms, however high level evidence consistently demonstrating efficacy
      is lacking. Further more robust trials are required to better understand which
      elements of energy healing interventions are associated with positive outcomes.

PMID- 27863609
TI  - The impact of listening to pleasant natural sounds on anxiety and physiologic
      parameters in patients undergoing coronary angiography: A pragmatic quasi
      randomized-controlled trial.
AB  - OBJECTIVE: This study aimed to investigate the impact of listening to pleasant
      natural sounds on anxiety and physiological parameters in patients undergoing
      coronary angiography. METHODS: The present pragmatic quasi-randomized controlled
      clinical trial was conducted on 130 patients undergone elective angiography. The
      participants were randomly divided into two groups, including a pleasant natural
      sounds group, and a control group (n1/2 65 per group). Spielberger's state/trait
      anxiety inventory was used to assess levels of anxiety. The patients' anxiety
      level and physiological parameters were measured at baseline, before, during,
      immediately after, and 20 min after coronary angiography. RESULTS: The mean level
      of anxiety was similar in both arms at baseline (t = 1.317, df = 128, p = 0.190).
      The intervention arm displayed significantly lower anxiety levels than the
      control arm during the intervention (Wilks' lambda 0.11, Pillai's trace 0.89, P
      0.001, F 2.05). The physiological parameters (systolic and diastolic blood
      pressure, mean arterial pressure, heart rate, and oxygen saturation) of both
      groups showed statistically significant differences (p < 0.05) over time and in
      group-by time interactions. CONCLUSION: As an effective nursing intervention
      presenting no side-effects, listening to pleasant natural sounds can be helpful
      in the management of anxiety.

PMID- 27863610
TI  - Exploring the body through reflexology: Physical behaviors observed during
      application.
AB  - Recent studies on reflexology describe the appearance of different application
      associated effects, attributed to a self-regulatory mechanism related to
      treatment efficacy. On the other hand, sleep is a physiological process of vital
      importance for health. Its main value lies in restoring the natural balance
      between neuronal centers. Among its associated behavioral characteristics are
      spontaneous movements and eye movements. The aim of this study is to investigate
      the effects that occur during application of reflexology and that are not
      described in the literature. This is a descriptive observational study with a
      quantitative methodology. Abivariate anlysis has been conductec through chi
      square test or Anova as apropiate. A total of 111 clients of a therapy center in
      Tarragona have participated in the study. They were assigned into four groups
      (musculoskeletal, stress, anxiety, mantenance). Reflexology was administered and
      observered the manifestations that occured during the session. The findings have
      identified four categories of effects, of which there was no previous reference.
      These effects can be related to any of the stages of sleep. This study shows that
      reflexology promotes its application for different effects, such as eye movements
      and spontaneous movements. These data reveal the need to investigate these
      effects and their impact on health as well as their possible relationship with
      sleep.

PMID- 27863611
TI  - Mindfulness based stress reduction adapted for depressed disadvantaged women in
      an urban Federally Qualified Health Center.
AB  - BACKGROUND: In this study we examine the feasibility and preliminary
      effectiveness of mindfulness based stress reduction adapted for delivery in an
      urban Federally Qualified Health Center (FQHC). METHODS: Thirty-one African-
      American adult women ages 18-65 with depressive symptoms enrolled to participate
      in an 8-week mindfulness group intervention. The primary outcome (depression) and
      secondary outcomes (stress, mindfulness, functioning, well-being, and depression
      stigma) were assessed at baseline, 8 and 16-weeks. RESULTS: Depressive symptoms
      significantly decreased from baseline to 16 weeks. A significant decrease in
      stress and significant increase in mindfulness was found from baseline to 8 weeks
      and baseline to 16 weeks. Additionally, aspects of well-being-self-acceptance and
      growth-significantly increased from baseline to 8-weeks. Stigma significantly
      increased from baseline to 8 weeks and significantly decreased from 8 to 16 weeks
      (all p's < 0.05). CONCLUSIONS: Mindfulness-based interventions implemented in
      FQHCs may increase access to effective treatments for mental health symptoms.

PMID- 27863612
TI  - Complementary and alternative medicine use in children with cystic fibrosis.
AB  - PURPOSE: To estimate the overall prevalence of complementary and alternative
      medicine use among children with cystic fibrosis, determine specific modalities
      used, predictors of use and subjective helpfulness or harm from individual
      modalities. RESULTS: Of 53 children attending the cystic fibrosis clinic in
      London, Ontario (100% recruitment), 79% had used complementary and alternative
      medicine. The most commonly used modalities were air purifiers, humidifiers,
      probiotics, and omega-3 fatty acids. Family complementary and alternative
      medicine use was the only independent predictor of overall use. The majority of
      patients perceived benefit from specific modalities for cystic fibrosis symptoms.
      CONCLUSIONS: Given the high frequency and number of modalities used and lack of
      patient and disease characteristics predicting use, we recommend that health care
      providers should routinely ask about complementary and alternative medicine among
      all pediatric cystic fibrosis patients and assist patients in understanding the
      potential benefits and risks to make informed decisions about its use.

PMID- 27863613
TI  - Effect of aromatherapy massage with lavender essential oil on pain in patients
      with osteoarthritis of the knee: A randomized controlled clinical trial.
AB  - BACKGROUND: Osteoarthritis of the knee is the most common chronic joint disease
      that involves middle aged and elderly people. The purpose of this study was to
      investigate the effect of aromatherapy massage with lavender essential oil on
      pain in patients with osteoarthritis of the knee. METHODS: In this single
      blinded, randomized clinical trial, 90 patients with osteoarthritis of the knee
      who referred to the outpatient rheumatology clinics affiliated with Birjand
      University of Medical Sciences were selected through convenience sampling method.
      They were randomly assigned to three groups: intervention (aromatherapy massage
      with lavender essential oil), placebo (massage with almond oil) and control
      (without massage). The patients were evaluated at baseline, immediately after the
      intervention, 1 week, and 4 weeks after the intervention in terms of pain via
      visual analogue scale. The data were analyzed in SPSS (version 16) using the
      repeated measure ANOVA, one-way ANOVA, and chi-squared test. RESULTS: Pain
      severity of the patients in the intervention group was significantly different
      immediately and 1 week after the intervention compared with their initial status
      (p < 0.001) and that of the control group (p < 0.001 and p = 0.009 respectively).
      However, at the third phase of follow-up (i.e., 4 weeks after the intervention),
      there was no significant difference between the groups according to the visual
      analogue scale (p = 0.67). CONCLUSION: Aromatherapy massage with lavender
      essential oil was found effective in relieving pain in patients with knee
      osteoarthritis. However, further studies are needed to confirm findings of this
      study.

PMID- 27863614
TI  - Guided imagery effects on chemotherapy induced nausea and vomiting in Iranian
      breast cancer patients.
AB  - BACKGROUND: The objective of this study was to examine the effect of guided
      imagery on chemotherapy induced nausea and vomiting in breast cancer patients.
      DESIGN: This was a quasi-experimental study in which a group of sample was
      evaluated pre and post intervention. A convenience sample of 55 eligible breast
      cancer patients enrolled to participate in this study after giving informed
      consent. They completed the Morrow Assessment of Nausea and Vomiting, before and
      after the intervention. The intervention consisted of listening to the two guided
      imagery tracks. FINDINGS: After the intervention, patients at the third session
      of chemotherapy had significantly lower mean scores in the frequency and severity
      of nausea and vomiting pre and post chemotherapy (p < 0.05). CONCLUSIONS: Guided
      imagery, as an inexpensive and noninvasive method, is particularly appealing
      option to alleviate chemotherapy induced nausea and vomiting. It can be used in
      addition to pharmacological strategies and can be implemented by patients
      independently with sufficient training. Therefore, this therapy will considerably
      improve severity and frequency of chemotherapy induced nausea and vomiting.

PMID- 27863615
TI  - The effect of aromatherapy with lavender essence on severity of labor pain and
      duration of labor in primiparous women.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of Lavender
      essence inhalation on severity of labor pain and duration of labor. METHODS AND
      MATERIALS: This single-blind, randomized clinical trial was conducted on 120
      pregnant women in two groups. The experimental group received 2 drops of Lavender
      essence inhaled at three stages (4-5, 6-7, 8-9 cm cervical dilation) and severity
      of the labor pain and duration of labor was measured before and after
      intervention. The control group was treated with distilled water as a placebo in
      the similar ways, too. RESULTS: The results showed that difference in the labor
      pain before and after intervention in two groups was significant (P = 0/001). But
      there was no difference in mean duration of the active phase and the second stage
      of labor between the two groups. CONCLUSION: Lavender essence aromatherapy may be
      an effective therapeutic option for pain management for women in labor.

PMID- 27863616
TI  - Attitudes, beliefs and behaviours of Australia dietitians regarding dietary
      supplements: A cross-sectional survey.
AB  - BACKGROUND: The aim of this study was to investigate the attitudes, beliefs and
      behaviors of Australian dietitians regarding dietary supplements. METHODS: An
      online survey was disseminated through the mailing lists of multiple healthcare
      organizations. There were 231 Australian dietitians that replied to the online
      survey. RESULTS: The results indicate that Australian dietitians are interested
      in dietary supplements (65%); however, the results also indicate that Australian
      dietitians are tentative about integrating dietary supplements into their
      dietetic practice. Concerns regarding potential drug-nutrient/herbal interactions
      were reported as the primary barrier (67%) to utilizing dietary supplements as
      part of clinical practice. In addition, there was a strong interest in additional
      training in dietary supplements (79%). CONCLUSIONS: In summary, Australian
      dietitians are interested in the use of dietary supplements; however, due to
      current barriers, few dietitians utilize dietary supplements as part of dietetic
      practice.

PMID- 27863617
TI  - Effectiveness of SP6 (Sanyinjiao) acupressure for relief of primary dysmenorrhea
      symptoms: A systematic review with meta- and sensitivity analyses.
AB  - We reviewed the available evidence for SP6 (Sanyinjiao) acupressure for the
      relief of primary dysmenorrhea (PD) symptoms, as well as patients' experiences of
      this intervention. We searched six relevant databases and gray literature for
      publications dated up to March 2016. The search yielded 72 potential studies. Six
      of these studies, contributing a total of 461 participants, were included in this
      review. The primary outcome was pain intensity. Studies with significant
      homogeneity were pooled for meta-analysis. Qualitative data and quantitative data
      not suitable for meta-analysis were presented as a narrative synthesis. The
      Cochrane criteria demonstrated that the included studies were generally of low
      quality with a high risk of bias. SP6 acupressure delivered by trained personnel
      significantly decreased pain intensity immediately after the intervention (effect
      size = -0.718; CI = -0.951 to -0.585; p = 0.000), and pain relief remained up to
      3 h after the intervention (effect size = -0.979; CI = -1.296 to 0.662; p =
      0.000). However, patient-administered intervention required multiple monthly
      cycles to effect pain reduction. SP6 acupressure appears to be effective when
      delivered by trained personnel for some PD symptoms. Findings suggest that self
      administered acupressure shows promise for the alleviation of PD symptoms. High
      quality research is needed before conclusive recommendations are proposed.

PMID- 27863619
TI  - Identification of SLC26A4 mutations p.L582LfsX4, p.I188T and p.E704K in a Chinese
      family with large vestibular aqueduct syndrome (LVAS).
AB  - Large vestibular aqueduct syndrome (LVAS) is a type of hearing loss characterized
      by an autosomal recessive inheritance. LVAS has been shown to be associated with
      mutations in SLC26A4 gene. In the present study, we report the clinical, genetic
      and molecular characterization of a Chinese family with LVAS. By using the
      targeted sequence capture and next-generation sequencing, we identified
      heterozygous mutations of SLC26A4 p.I188T (c.563T > C), p.L582LfsX4 (c.1746 delG)
      and p.E704K (c.2110G > A) in the affected individual of this family, of which
      SLC26A4 p.E704K is a novel mutation associated with LVAS. By tracing the
      transmission and functional prediction of these mutations in the pedigree, the
      heterozygous mutations of p.I188T, p.L582LfsX4 and p.E704K in SLC26A4 gene were
      responsible for the LVAS of the affected individual. This is the first case of
      LVAS caused by these mutations.

PMID- 27863620
TI  - Paediatric airway foreign body - The human factors influencing patient safety in
      our hospitals.
AB  - Foreign bodies in the pediatric airway are an uncommon emergency with a high
      morbidity and mortality rate. Morbidity ranges from 10 to 20% worldwide and this
      pathology accounts for up to 7% of accidental deaths in children under 4. Dealing
      with this emergency safely and effectively is complex, requiring a tight coupling
      of procedures and processes and optimal anesthetic and operating conditions to
      prevent errors. These factors are recognized by the World Health Organization as
      'Human Factors'. We perform a multi-center assessment of human factors pertinent
      to this emergency. Specifically, equipment provision and staff training in this
      emergency. Data was collected from 13 sites in the United Kingdom, using two
      questionnaires for medical and nursing staff. Information including equipment
      availability, location of equipment, and surgeon and nursing experience was
      recorded. Royal Manchester Children's Hospital (RMCH) set the study standard. Our
      study shows there is huge variability in equipment provision across units. There
      is a lack of experience, confidence and training amongst middle grade
      otolaryngology surgeons and emergency theatre staff in handling this emergency.
      Issues with equipment and inexperience of both middle grade doctors and nursing
      staff could result in significant patient morbidity and mortality. We suggest a
      standardized age appropriate equipment list and staff training in use of this
      equipment. Implementation of these simple changes could reduce preventable error
      in this rare but serious emergency.

PMID- 27863621
TI  - Impact of adenotonsillectomy on the quality of life in children with sleep
      disordered breathing.

PMID- 27863622
TI  - Objective characterization of airway dimensions using image processing.
AB  - OBJECTIVES: With the evolution of medical and surgical management for pediatric
      airway disorders, the development of easily translated techniques of measuring
      airway dimensions can improve the quantification of outcomes of these
      interventions. We have developed a technique that improves the ability to
      characterize endoscopic airway dimensions using common bronchoscopic equipment
      and an open-source image-processing platform. METHODS: We validated our technique
      of Endoscopic Airway Measurement (EAM) using optical instruments in simulation
      tracheas. We then evaluated EAM in a large animal model (Ovis aries, n = 5),
      comparing tracheal dimensions obtained with EAM to measurements obtained via 3-D
      fluoroscopic reconstruction. The animal then underwent resection of the measured
      segment, and direct measurement of this segment was performed and compared to
      radiographic measurements and those obtained using EAM. RESULTS: The simulation
      tracheas had a direct measurement of 13.6, 18.5, and 24.2 mm in diameter. The
      mean difference of diameter in simulation tracheas between direct measurements
      and measurements obtained using EAM was 0.70 +/- 0.57 mm. The excised ovine
      tracheas had an average diameter of 18.54 +/- 0.68 mm. The percent difference in
      diameter obtained from EAM and from 3-D fluoroscopic reconstruction when compared
      to measurement of the excised tracheal segment was 4.98 +/- 2.43% and 10.74 +/-
      4.07% respectively. Comparison of these three measurements (EAM, measurement of
      resected trachea, 3-D fluoroscopic reconstruction) with repeated measures ANOVA
      demonstrated no statistical significance. CONCLUSIONS: Endoscopic airway
      measurement (EAM) provides equivalent measurements of the airway with the
      improved versatility of measuring non-circular and multi-level dimensions. Using
      optical bronchoscopic instruments and open-source image-processing software, our
      data supports preclinical and clinical translation of an accessible technique to
      provide objective quantification of airway diameter.

PMID- 27863623
TI  - Tuberculous lymphadenitis of the head and neck in Canadian children: Experience
      from a low-burden region.
AB  - BACKGROUND: Children are more likely than adults to develop extra-pulmonary
      tuberculosis (EPTB), which often presents as cervical lymphadenopathy. The role
      of surgery in management is uncertain. We reviewed all head and neck EPTB cases
      presenting to our tertiary care pediatric institution over a twelve-year period.
      METHODS: All children 18 years of age and younger with EPTB involving the head
      and neck were included. We recorded clinical data and age at diagnosis, birth
      country, BCG vaccination status, as well as radiographic, surgical, histological,
      and microbiological results. RESULTS: All 16 patients presented with cervical
      lymphadenopathy. Fourteen were born outside of Canada in TB endemic areas and all
      had foreign-born parents. Diagnosis was confirmed microbiologically from lymph
      node biopsies in 14 cases. Multi-drug resistant TB was identified in two cases:
      both had previous excisional node biopsies that had not been cultured. Two
      patients had culture negative suppuration despite adequate anti-tuberculous
      treatment that required surgery for cure. CONCLUSION: Ongoing suppuration despite
      appropriate drug therapy is seen in a minority of patients. We found that
      excisional lymph node biopsy of diseased cervical lymph nodes is diagnostic, and
      also therapeutic in some cases with ongoing suppuration despite appropriate drug
      therapy. Mycobacterial culture of lymph nodes is important for diagnosis and
      determination of drug resistance patterns.

PMID- 27863624
TI  - Comparison of auditory comprehension skills in children with cochlear implant and
      typically developing children.
AB  - OBJECTIVE: The main goal of this study was to obtain auditory comprehension
      skills of native Hindi speaking children with cochlear implant and typically
      developing children across the age of 3-7 years and compare the scores between
      two groups. METHODOLOGY: A total of sixty Hindi speaking participants were
      selected for the study. They were divided into two groups- Group-A consisted of
      thirty children with normal hearing and Group-B thirty children using cochlear
      implants. To assess the auditory comprehension skills, Test of auditory
      comprehension in Hindi (TACH) was used. The participant was required to point to
      one of three pictures which would best correspond to the stimulus presented.
      Correct answers were scored as 1 and incorrect answers as 0. RESULTS: TACH was
      administered on for both groups. Independent t-test was applied and it was found
      that auditory comprehension scores of children using cochlear implant were
      significantly poorer than the score of children with normal hearing for all three
      subtests. Pearson's correlation coefficient revealed poor correlation between the
      scores of children with normal hearing and children using cochlear implant.
      CONCLUSION: The results of this study suggest that children using cochlear
      implant have poor auditory comprehension skills than children with normal
      hearing.

PMID- 27863625
TI  - Facial nerve stimulation following cochlear implantation for X-linked stapes
      gusher syndrome leading to identification of a novel POU3F4 mutation.
AB  - We report a case of a nine-year-old male who presented with facial nerve
      stimulation four years after cochlear implantation. Computed tomography was
      performed revealing a dilated internal auditory meatus and the cochlear implant
      electrode was found to be protruding into the fallopian canal at the level of the
      geniculate ganglion. Subsequent genetic analysis demonstrated X-linked deafness
      type 2 (DFNX2) caused by a novel c.769C > T nucleotide change in the POU domain,
      class 3, transcription factor 4 gene (POU3F4). Inactivation of electrodes 1 and
      19-21 successfully abated facial nerve stimulation.

PMID- 27863626
TI  - Temporalis myofascial flap coverage for extrusion of internal device after
      cochlear implantation.
AB  - Two pediatric patients with internal device exposure of cochlear implant (CI)
      were treated successfully using vascularized temporalis myofascial flaps. The
      visible scarring was minimal, and the CI function was excellent. Although we used
      temporalis myofascial flaps for late complications of an implanted ear, it can
      also be used in a primary case to provide flap reinforcement. In conclusion, the
      temporalis myofascial flap technique is an ultimate surgical option that offers
      advantages for CI patients with flap-related problems.

PMID- 27863627
TI  - A mismatch negativity study in Mandarin-speaking children with sensorineural
      hearing loss.
AB  - OBJECTIVE: a) To examine the effects of sensorineural hearing loss on the
      discriminability of linguistic and non-linguistic stimuli at the cortical level,
      and b) to examine whether the cortical responses differ based on the
      chronological age at intervention, the degree of hearing loss, or the acoustic
      stimulation mode in children with severe and profound hearing loss. METHODS:
      Mismatch negativity (MMN) responses were collected from 43 children with severe
      and profound bilateral sensorineural hearing loss, and 20 children with normal
      hearing (age: 3-6 years). In the non-verbal stimulation condition, pure tones
      with frequencies of 1 kHz and 1.1 kHz were used as the standard and the deviant
      respectively. In the verbal stimulation condition, the Chinese mandarin
      tokens/ba2/and/ba4/were used as the standard and the deviant respectively.
      Latency and amplitude of the MMN responses were collected and analyzed. RESULTS:
      Overall, children with hearing loss showed longer latencies and lower amplitudes
      of the MMN responses to both non-verbal and verbal stimulations. The latency of
      the verbal/ba2/-/ba4/pair was longer than that of the nonverbal 1 kHz-1.1 kHz
      pair in both groups of children. CONCLUSIONS: Children with hearing loss,
      especially those who received intervention after 2 years of age, showed
      substantial weakness in the neural responses to lexical tones and pure tones.
      Thus, the chronological age when the children receive hearing intervention may
      have an impact on the effectiveness of discriminating between verbal and non
      verbal signals.

PMID- 27863628
TI  - An effective compromise between cost and referral rate: A sequential hearing
      screening protocol using TEOAEs and AABRs for healthy newborns.
AB  - OBJECTIVE: This study evaluated the efficacy of a sequential hearing screening
      protocol using transient evoked otoacoustic emission (TEOAE) and automated
      auditory brainstem response (AABR) tests in healthy newborns. DESIGN: A TEOAE
      screening was performed during the first 48-72 h of life. If the infants failed,
      an AABR test was performed at the same time, and they were referred for a TEOAE
      rescreening at six weeks old. The results of screening Protocol 1 (only TEOAE)
      were compared with those of screening Protocol 2 (sequential TEOAE + AABR
      screenings for the first screening and TEOAE for the rescreening). STUDY SAMPLE:
      A total of 1062 healthy newborns were enrolled in this research. RESULTS: For
      Protocol 1, the first screening and rescreening referral rates were 11.1% and
      2.2%, respectively. In contrast, for Protocol 2, the referral rates were
      significant lower at 3.8% and 0.9%, respectively. Using the two protocols, six
      infants were diagnosed with hearing loss (0.57%). CONCLUSIONS: Adding
      simultaneous AABR tests for infants who fail TEOAE testing at the first screening
      stage can significantly reduce referral rates without increasing misdiagnosis
      rates. Although this sequential screening process involves slightly more time and
      has a higher cost than TEOAE alone, its greater accuracy compensates for this
      difference.

PMID- 27863629
TI  - Development of the maxillary sinus in infants and children.
AB  - OBJECTIVE: To examine the age related volume change of the maxillary sinus in
      children by measuring the change of the height, weight, and depth using computed
      tomography (CT). METHODS: Children <18 years of age who underwent a CT Scan of
      the sinuses for reasons other than sinus related issues were included in the
      study. RESULTS: 139 patients were included (68 females and 71 Males) and the mean
      age of the patients was 9.6 +/- 5.4 years. The cohort was divided into three
      groups based on their ages - Age <6 years (n = 45), age between 6 and 12 years (n
      = 44) and age > 12 years (n = 50). Patients in each age group demonstrated an
      increase in their Maxillary sinus height (p<0.001). Patients < 6years of age and
      between 6 and 12 years of age had a significant increase in their maxillary sinus
      width and depth (p < 0.001). The maxillary sinus width, depth and volume did not
      increase significantly after the age of 12 years in these patients. CONCLUSION:
      We demonstrated periods of significant size increase of the maxillary sinuses as
      determined by different dimensions in children at various ages. The height of the
      maxillary sinus has steady growth from birth to at least the age of 18 years. The
      width and depth increase up to 12 years of age.

PMID- 27863630
TI  - Comparison of treatment outcomes between intracapsular and total tonsillectomy
      for pediatric obstructive sleep apnea.
AB  - BACKGROUND: Intracapsular tonsillectomy (IT) has been advocated as a treatment
      for pediatric obstructive sleep apnea (OSA). However, evidence in the literature
      utilizing polysomnography (PSG) is limited. OBJECTIVE: To examine the experience
      at a tertiary children's hospital to evaluate the effectiveness and risks of
      intracapsular tonsillectomy compared to total tonsillectomy (TT) for treating
      pediatric OSA. METHODS: A retrospective study was undertaken of pediatric
      tonsillectomy cases performed for OSA at a tertiary children's hospital from 2005
      to 2010. Patients with recurrent tonsillitis, craniofacial abnormalities,
      chromosomal abnormalities, neuromuscular disease, and congenital malformations
      were excluded. Main outcome measures were apnea-hypopnea index (AHI), minimum
      oxygen saturation (minO2), and surgical complications. RESULTS: Of the 1583
      patients reviewed in this study, there were 75 IT and 93 TT patients with pre-
      and post-operative PSG results. The IT patients were younger, had lower BMI,
      larger tonsil size, lower pre-operative (AHI) and lower post-operative AHI (p <
      0.05). There was a similar percentage of patients that showed improvement in AHI
      and minimum oxygen saturation between the IT and TT groups. There were
      statistically similar average change in AHI and minimum oxygen saturation between
      the IT and TT groups at 5.6 +/- 8.6 and 8.6 +/- 12.9, respectively (p = 0.8) as
      well as similar improvement in minimum oxygen saturation between the two groups
      at 3.3% +/- 4.3% and 3.0% +/- 5.2%, respectively (p = 0.66). Of TT patients, 2.9%
      experienced post-operative bleeding with 1.6% requiring OR for control of
      hemorrhage. Of IT patients, 2.2% were found to have tonsillar regrowth with 2.0%
      returning to the OR for secondary tonsillectomy. CONCLUSIONS: Intracapsular
      tonsillectomy, like total tonsillectomy, is effective in improving polysomnogram
      results in appropriately selected children. Intracapsular tonsillectomy is a
      suitable option for the surgical treatment of pediatric OSA consequent to its
      demonstrated efficacy in relieving OSA and its favorable safety profile.

PMID- 27863631
TI  - Diagnostic hearing testing of infants aged 0-36 months in 3 South African
      provinces - Comparison of audiology records to HPCSA guidelines.
AB  - INTRODUCTION: Within the Early Hearing Detection and Intervention (EHDI) pathway,
      which includes the processes of screening, diagnosis and intervention for
      paediatric hearing loss, paediatric diagnostic audiology involves a battery of
      specific tests and procedures. International studies have highlighted a golden
      standard for diagnosis of paediatric hearing loss as based on the Joint Committee
      of Infant Hearing (2007) diagnostic guidelines, closely resembling the HPCSA
      diagnostic guidelines. There are limited South African studies on the processes
      and protocols followed in diagnostic paediatric audiology. OBJECTIVES: This study
      aims to provide a comparison for how the tests used for diagnosis of paediatric
      hearing loss in South Africa (within both the public and private healthcare
      sectors) compare to the HPCSA recommended diagnostic guidelines. METHODS: A
      retrospective record review of paediatric clients with hearing loss (recruited
      through nonprobability convenience sampling) was conducted. This study is part of
      a longitudinal study of 711 deaf or hard of hearing children referred to the HI
      HOPES early intervention programme from September 2006 to December 2011.
      Diagnostic data from audiology reports of 117 children between 0 and 36 months
      were coded and analysed. RESULTS: Large variation was found in the tests included
      in the diagnostic audiology reports. For 22 children (19%) a comprehensive test
      battery was used. Health Professions Council of South Africa (HPCSA) recommended
      guidelines for diagnostic testing were not followed in any of the records
      analysed. Components of the HPCSA recommended test battery most frequently
      omitted was bone conduction testing. For both electrophysiology and behavioural
      testing, there was limited frequency specificity information. This exclusion of
      information is evidence of deficiencies in data recording and management, as well
      as having an effect on accuracy of classification of degree and type of hearing
      loss. CONCLUSION: There are gaps in age-appropriate assessment protocols, which
      will have an effect on accurate differential diagnosis of paediatric hearing
      loss. Reasons for not including all testing components of the HPCSA recommended
      guidelines, as well as the possibility of developing guidelines more relevant to
      a developing world context, should be explored. There might be a need for. The
      impact of South African specific factors that have an effect on provision of
      accurate paediatric diagnostic audiology services should be determined.

PMID- 27863632
TI  - Soft-wall reconstruction of the canal wall with retrograde bone work for
      pediatric cholesteatoma: Long-term results.
AB  - OBJECTIVE: To retrospectively evaluate the long-term results of surgery for
      retrograde bone work, using soft-wall reconstruction of the canal wall, for
      pediatric cholesteatoma. METHODS: We retrospectively evaluated a series of 25
      consecutive ears of 24 patients who were <=16 years of age. All children
      underwent cholesteatoma surgery between October 2002 and August 2008. The type of
      cholesteatoma, the length of follow-up, the incidence of residual and recurrent
      cholesteatoma, postoperative hearing results, and the form of the reconstructed
      external canal wall and tympanic membrane were assessed. RESULTS: There were 21
      males and 3 females. The procedure was performed on both ears of one patient who
      had bilateral congenital cholesteatoma (CC). At the initial surgery, 16 cases
      (64%) had CC and nine (36%) had acquired cholesteatoma (AC). The mean age at
      surgery was 8.2 years and 10.4 years for CC and AC cases, respectively. The mean
      postoperative follow-up period after the initial surgery was 90 months for CC
      cases and 108 months for AC cases. Cholesteatoma recurrence occurred for 6% and
      56% of cases with CC and AC, respectively. Successful serviceable hearing was
      achieved for 93.8% with CC and 100% with AC. Cases with inadequate hearing after
      surgery were characterized by disease extension to the mastoid and the
      protympanum. The long-term forms of the reconstructed external canal wall changed
      depending on their middle ear aeration. Some cases of tympanic membrane
      perforation and otitis media with effusion were occurred during the follow-up
      period. CONCLUSION: Overall, the retrograde approach with soft-wall
      reconstruction of the canal wall achieved a low recurrence rate for cholesteatoma
      and good hearing outcomes during long-term follow-up for the pediatric case.
      However, in cases with eustachian tube dysfunction and/or cholesteatoma involving
      the protympanum, the hearing outcomes were less favorable.

PMID- 27863633
TI  - Intersurgical interval increased with use of quadrivalent human papillomavirus
      vaccine (Gardasil) in a pediatric patient with recurrent respiratory
      papillomatosis: A case report.
AB  - This is a case of a 4 year old female with recalcitrant recurrent respiratory
      papillomatosis with decreasing intersurgical interval that had improvement in
      clinical course after administration of the quadrivalent HPV vaccine.

PMID- 27863634
TI  - Predictors of flourishing among children with hearing loss.
AB  - OBJECTIVES: To examine parent report of flourishing in children with hearing
      impairments compared to children without hearing impairments, and to explore
      whether school engagement and bullying related to child flourishing. METHODS:
      Participants were 655 children with hearing impairments and 44, 618 children
      without hearing impairments who were 10-17 years of age. Caregivers completed
      telephone interviews about their child's functioning for the National Survey of
      Children's Health. RESULTS: Children without hearing loss had higher parent
      reported flourishing compared to children with hearing loss when controlling for
      child demographics (i.e., race, age, sex). School engagement was positively
      related to flourishing of children with hearing loss. Bullying behaviors were not
      related to flourishing of children with hearing loss. CONCLUSION: Improving
      school engagement may increase flourishing of children with hearing loss, which
      is critical given that children with hearing loss experience lower flourishing
      than children without hearing loss. Examining the relationships among other risk
      and resilience factors and flourishing for children with hearing loss will
      provide information for interventions to enhance the adaptation of these
      children.

PMID- 27863635
TI  - Cochlear implantation of solid organ transplant patients receiving
      immunosuppressive therapy.
AB  - OBJECTIVE: To evaluate the incidence of infectious complications and healing
      problems in cochlear implant (CI) patients receiving immunosuppressive therapy
      following solid organ transplant. STUDY DESIGN: IRB-approved retrospective chart
      review of implanted patients. SETTING: Tertiary care children's hospital.
      METHODS: Seven patients of the more than 1000 implanted during the time period
      between 1991 and 2014 underwent cochlear implantation while on immunosuppressive
      therapy after having received a solid organ transplant. Their charts were
      reviewed for demographic and medical information pre- and post-implantation. The
      4 males and 3 females ranged in age at CI from 2.4 to 18.8 years, with a mean of
      9.0 years. Postimplant follow-up averaged 3.9 years (range: 0.1-13.1). Main
      outcome measures were occurrence of wound healing, infectious complications,
      whether open-set word recognition was achieved, and communication mode(s).
      RESULTS: No wound infections or delayed healing, mastoiditis, or bacterial
      meningitis occurred after cochlear implantation. All seven patients had received
      at least one pneumococcal vaccination prior to implantation. Five of 6 (83%)
      developed open-set speech perception, of whom 4 (67%) use only oral
      communication. CONCLUSION: In our series of patients receiving immunosuppressive
      therapy following solid organ transplantation, none developed wound healing or
      infectious complications after cochlear implantation. History of solid organ
      transplantation alone should not be a contraindication to cochlear implant
      candidacy which would deprive the child of the potential benefits of hearing,
      including language development.

PMID- 27863636
TI  - The effect of propofol infusion with topical epinephrine on cochlear blood flow
      and hearing: An experimental study.
AB  - BACKGROUND AND OBJECTIVE: Propofol is the most commonly used intravenous (IV)
      anesthetic agent and is associated with hypotension upon induction of anesthesia.
      Intravenous propofol infusion has several properties that may be beneficial to
      patients undergoing middle ear surgery. Topical application of concentrated
      epinephrine is a valuable tool for achieving hemostasis in the middle ear and
      during mastoid surgery. The purpose of the present study was to determine the
      effects of propofol infusion with topical epinephrine on cochlear blood flow
      (CBF) and hearing in rats. MATERIALS AND METHODS: Twenty one male Sprague-Dawley
      rats were divided into three groups. The rate of intravenous infusion of propofol
      was 4-6 ml/kg/hour. The first group (control group, n = 7) was given IV infusion
      of phosphate buffered saline (PBS) with topical application of PBS in the round
      window. In study group A (n = 7), the effect of topical phosphate buffered saline
      with IV infusion of propofol on CBF and hearing was evaluated. In study group B
      (n = 7), additional effects of topical epinephrine with IV infusion of propofol
      on CBF and hearing were evaluated. The laser Doppler blood flowmeter, CBF, and
      the mean arterial blood pressure (MAP) were measured and analyzed. Additionally,
      hearing test using auditory brainstem response (ABR) was performed in both
      groups. RESULTS: In both groups, infusion of propofol induced a time-dependent
      decrease in MAP. Approximately 30 min after the start of the propofol infusion,
      the CBF started to decrease slowly. The decrease in CBF was significantly greater
      in the study group compared to the control group. The threshold was elevated in
      the study group relative to the control group. CONCLUSION: During middle ear
      surgery, use of IV infusion of propofol with topical epinephrine cotton ball or
      cottonoid application is not recommended.

PMID- 27863637
TI  - Nasal septal abscess in association with pediatric acute rhinosinusitis.
AB  - INTRODUCTION: Nasal septal abscess (NSA) in the pediatric population is rare and
      can result in devastating complications. Objective of this study is to review a
      case series of pediatric patients presenting with NSA in association with acute
      rhinosinusitis (ARS) for possible risk factors and predisposing conditions.
      METHOD: This is a retrospective review of pediatric patients that presented to a
      tertiary care hospital with nasal septal abscess associated with ARS. Patient
      demographics, presence of ARS, sinuses involved, and other potential risk factors
      were recorded. In addition, a literature review was conducted to evaluate other
      reported cases of NSA in association with ARS. Cases of NSA associated with
      trauma or other causes were excluded from analysis. RESULTS: Five patients with
      NSA were treated by the pediatric otolaryngology department of a tertiary care
      center from 2003 to 2014. Three of these cases were associated with ARS. Of these
      cases, the average age at diagnosis was 9.7 years. Two were male and one was
      female. In these cases, the bilateral frontal, maxillary and ethmoid sinuses were
      involved. Sphenoid involvement occurred in two patients. One case was associated
      with ipsilateral middle turbinate concha bullosa. The cartilaginous septum was
      compromised in all three cases. All patients were treated with incision and
      drainage. CONCLUSION: This is the largest case series of NSA described in the
      pediatric population. NSA is exceedingly rare but may be associated with ARS.
      While the etiology of NSA is not always clear, identifying and treating nasal
      septal abscesses early is imperative to reduce potentially devastating
      complications.

PMID- 27863638
TI  - Comparison of the effects of lipoic acid and glutathione against cisplatin
      induced ototoxicity in auditory cells.
AB  - OBJECTIVES: The aims of this study were to examine lipoic acid (LA)- or
      glutathione (GSH)-mediated protection against cytotoxicity following cisplatin
      exposure in HEI-OC1 auditory cells and measure the potential of LA and GSH to
      scavenge reactive oxygen species (ROS). This study also compares their protective
      effects and discusses the determination of a preventive or therapeutic dose.
      METHODS: HEI-OC1 cells were pretreated with LA or GSH for 24 h and then exposed
      to 15 MUM cisplatin for 48 h. The resulting cytotoxicity was measured using a
      cell counting kit-8, and intracellular ROS level was measured using flow
      cytometry. The protective or anti-ROS effects of LA and GSH were compared.
      Measurement of caspase 3, 8, 9 activity and Western blot analysis of PARP were
      performed. RESULTS: Pretreatment with LA at 300 MUM and GSH at 3 mM protected HEI
      OC1 cells against cisplatin-induced cytotoxicity and significantly reduced the
      cisplatin-induced increase in ROS. LA showed a significantly more effective
      protection against cisplatin-induced ototoxicity compared to that shown by GSH
      (85.4% vs. 73.1% cell viability). Both LA and GSH showed the maximal protective
      effect at different concentrations in normal or cisplatin-induced cytotoxic
      conditions. The preventive or therapeutic dose for harmful conditions is quite
      different for the two drugs and needs careful adjustments. CONCLUSION: This
      comparative study on the protective effects of LA and GSH against cisplatin
      induced ototoxicity in an auditory cell line posed many challenges. Although LA
      and GSH showed a significant protective effect against cisplatin, the LA's effect
      was superior. The concentration at which the maximal protective effect of LA or
      GSH was noted was 3 times higher in cytotoxic conditions than in normal
      conditions, which suggests the need for drug dose adjustments based on the
      purpose (preventive or therapeutic).

PMID- 27863639
TI  - Conversion of traditional osseointegrated bone-anchored hearing aids to the
      Baha(r) attract in four pediatric patients.
AB  - Bone-anchored hearing aids are external devices attached to the skull via a
      titanium implant, and can be used for multiple types of hearing loss.
      Traditionally, osseointegrated implants have been coupled to the external
      processor with a percutaneous abutment, but more recently, a fully implanted,
      transcutaneous magnet-based system has become available. Skin reactions from the
      percutaneous portion are a common complication that can prevent use of the device
      during critical windows of language development and learning in children. We
      describe our experience replacing the Baha(r) abutment system with the Baha(r)
      Attract in four pediatric patients. Specific operative considerations for
      incision placement, and magnet and implant coverage are discussed. All patients
      maintained osseointegration, had excellent long-term wound healing without post
      operative infection, and were able to wear their devices more consistently.

PMID- 27863640
TI  - Assessment of adenotonsillar size and caregiver-reported sleep symptoms among 3-6
      year old children undergoing adenotonsillectomy.
AB  - INTRODUCTION: Adenotonsillectomy remains the accepted first-line treatment for
      obstructive sleep apnea syndrome (OSAS) in children. Tonsillar size may be
      especially relevant in risk stratification as it may impact symptoms of sleep
      disordered breathing (SDB). This study assesses correlations among subjective
      tonsillar grading, measured tonsillar size, and degree of adenoid obstruction in
      patients age 3-6 years with caregiver-reported symptoms. METHODS: Children 3-6
      years old undergoing adenotonsillectomy for OSAS were enrolled prospectively. The
      subjective tonsillar grade and degree of adenoid obstruction were recorded on
      physical examination by the otolaryngologist, and the objective tonsillar size
      was obtained from pathology reports. Spearman's rho was used to assess agreement
      among measures of tonsillar size and adenoid obstruction; and to correlate these
      measures with caregiver-reported SDB symptoms obtained from a pre-operative
      standardized questionnaire. RESULTS: The cohort included 103 boys and 97 girls of
      median age 4.8 (interquartile range [IQR]: 3.9, 5.9) years. Median subjective
      tonsillar grade was 3+ (IQR: 3+, 4+) while median tonsillar size was 2.7 cm (IQR:
      2.5, 3) and median adenoid obstruction was 60% (IQR: 50%, 80%). The subjective
      tonsillar grade and measured tonsillar size were strongly correlated (rho = 0.31,
      p < 0.001), whereas adenoid obstruction was uncorrelated with either subjective
      tonsillar grade (rho = 0.01, p = 0.860) or measured size (rho = -0.05, p =
      0.497). Tonsillar grade was positively correlated with 3 common caregiver
      reported SDB symptoms (loud snoring, trouble breathing at night, and daytime
      sleepiness). Objective tonsillar size was positively correlated only with
      difficulty organizing tasks or activities, and adenoid obstruction was positively
      correlated only with stopping breathing during sleep. CONCLUSION: Subjective
      tonsillar grading by the otolaryngologist achieved better correlation than
      measured tonsillar size or degree of adenoid obstruction with caregiver-reported
      SDB symptoms in children 3-6 years of age undergoing adenotonsillectomy.

PMID- 27863641
TI  - The influence of pediatric tracheostomy on the body weight percentile of
      children.
AB  - OBJECTIVES: The purpose of this study was to evaluate the changes in body weight
      following tracheostomy in pediatric patients. METHODS: Ninety-eight patients who
      underwent tracheostomy at the age of 0-6 years were enrolled. The body weight and
      growth percentile were measured before tracheostomy and at 1, 6, and 12 months
      after surgery. The body weight and growth percentile were plotted against time,
      which was compared with Korean growth chart curve. A Retrospective observational
      cohort study was performed. RESULTS: The mean body weight increased gradually
      from 6.7 (+/-0.51) kg to 10.84 (+/-0.15) kg at 12 months post-surgery (p < 0.01).
      The growth percentile also increased from 24.41 (+/-3.18) to 40.6 (+/-4.10)
      during the follow-up period (p < 0.01). We analyzed the patients with a low
      growth percentile (<=50th percentile). In these patients, the mean body weight
      increased from 4.92 (+/-0.27) kg to 8.97 (+/-0.27) kg and the growth percentile
      also increased from 11.02 (+/-1.32) to 30.56 (+/-3.31) (all p < 0.01). Ventilator
      independent patients also presented similar pattern of body weight and its
      percentile. CONCLUSIONS: Body weight increased after tracheostomy that was safely
      performed in children requiring airway management.

PMID- 27863642
TI  - Tissue-engineered trachea: A review.
AB  - Tracheal replacement is performed after resection of a portion of the trachea
      that was impossible to reconnect via direct anastomosis. A tissue-engineered
      trachea is one of the available options that offer many advantages compared to
      other types of graft. Fabrication of a functional tissue-engineered trachea for
      grafting is very challenging, as it is a complex organ with important components,
      including cartilage, epithelium and vasculature. A number of studies have been
      reported on the preparation of a graftable trachea. A laterally rigid but
      longitudinally flexible hollow cylindrical scaffold which supports cartilage and
      epithelial tissue formation is the key element. The scaffold can be prepared via
      decellularization of an allograft or fabricated using biodegradable or non
      biodegradable biomaterials. Commonly, the scaffold is seeded with chondrocytes
      and epithelial cells at the outer and luminal surfaces, respectively, to hasten
      tissue formation and improve functionality. To date, several clinical trials of
      tracheal replacement with tissue-engineered trachea have been performed. This
      article reviews the formation of cartilage tissue, epithelium and
      neovascularization of tissue-engineered trachea, together with the obstacles,
      possible solutions and future. Furthermore, the role of the bioreactor for in
      vitro tracheal graft formation and recently reported clinical applications of
      tracheal graft were also discussed. Generally, although encouraging results have
      been achieved, however, some obstacles remain to be resolved before the tissue
      engineered trachea can be widely used in clinical settings.

PMID- 27863643
TI  - The safety and efficacy of pediatric lingual tonsillectomy.
AB  - OBJECTIVE: Lingual tonsillar hypertrophy is recognized as a cause of persistent
      obstructive sleep apnea (OSA) after adenotonsillectomy in children. However,
      little has been reported regarding the complications, postoperative course and
      effectiveness of lingual tonsillectomy (LT). Our objective was to review the
      safety and effectiveness of LT in children. METHODS: Retrospective review of
      children undergoing LT from January 2009 to December 2015 at a tertiary
      children's hospital. Complications, postoperative course and polysomnographic
      (PSG) outcomes were recorded for all patients. RESULTS: We identified 92 children
      (mean age = 8.6 years, 50% female) who underwent LT; 43.5% had a syndromic
      diagnosis. The most common complications were emergency department presentation
      for bleeding (4.4%) and poor oral intake (3.3%). The readmission rate was 4.4%
      including 2 children (2.2%) who required operative control of hemorrhage. No
      children required unplanned reintubation or ICU admission. In children with PSG
      data (n = 18), the median apnea-hypopnea index (AHI) decreased from 8.5 to 3.8
      events/hour (p = 0.022) and the median obstructive AHI (oAHI) decreased from 8.3
      to 3.1 events/hour (p = 0.021). In addition, the oxygen saturation nadir
      increased from 83.8% to 89.0% (p = 0.0007). After surgery the percentage of
      patients with oAHI<5 events/hour increased from 27.8% to 61.1% (p = 0.08).
      CONCLUSIONS: Readmission and bleeding rates after lingual tonsillectomy in
      children were similar to that seen with tonsillectomy. Polysomnographic data
      showed that lingual tonsillectomy resulted in a significant reduction of both AHI
      and oAHI with a postoperative oAHI <5 achieved in 61% of patients.

PMID- 27863644
TI  - Ultrasound-guided removal of impalpable, radiolucent vegetative foreign bodies
      embedded into facial soft tissues of a toddler.
AB  - Otolaryngologists frequently encounter children with foreign bodies retained
      inside the lumen of their upper aerodigestive tract. However, total capture in
      the soft tissues happens rarely, and could be clinically, as well as
      radiographically, silent. Ultrasonography is a safe and effective imaging
      modality, aiding both diagnosis and surgical treatment. We report on a 14-month
      girl with chronic, fluctuating cheek edema and erythema, induced by an
      impalpable, radiolucent bundle of organic fibers embedded intramuscularly.
      Foreign body identification and atraumatic removal were facilitated by real-time
      ultrasound scanning.

PMID- 27863645
TI  - Identification of a de novo mutation of SOX10 in a Chinese patient with
      Waardenburg syndrome type IV.
AB  - OBJECTIVES: Waardenburg syndrome is a rare genetic disorder, characterized by the
      association of sensorineural hearing loss and pigmentation abnormalities. Four
      subtypes have been classified. The present study aimed to analyze the clinical
      feature and investigate the genetic cause for a Chinese case of Waardenburg type
      IV (WS4). METHODS: The patient and his family members were subjected to mutation
      detection in the candidate gene SOX10 by Sanger sequencing. RESULTS: The patient
      has the clinical features of WS4, including sensorineural hearing loss, bright
      blue irides, premature graying of the hair and Hirschsprung disease. A novel
      heterozygous frameshift mutation, c.752_753ins7 (p.Gly252Alafs*31) in the exon 5
      of SOX10 was detected in the patient, but not found in the unaffected family
      members and 100 normal controls. This mutation results in a premature stop codon
      31 amino acid downstream. CONCLUSIONS: The novel mutation c.752_753ins7
      (p.Gly252Alafs*31) arose de novo and was considered as the cause of WS4 in the
      proband. This study further characterized the molecular complexity of WS4 and
      provided a clinical case for genotype-phenotype correlation studies of different
      phenotypes caused by SOX10 mutations.

PMID- 27863646
TI  - Regenerative efficacy of mesenchymal stromal cells from human placenta in
      sensorineural hearing loss.
AB  - INTRODUCTION: Hearing loss is a common chronic disorder characterized by decline
      of auditory function. The global population have suffered from deafness and the
      transplantation of stem cells is regarded as a therapeutic strategy for this
      disease. METHODS: We collected placenta from a total of 13 samples of full term
      pregnant women and isolated MSCs derived from human placenta and transplanted
      MSCs on deaf animal model. The normal group and the sensorineural hearing loss
      (SNHL) group and the experimental (transplanted MSCs) group were compared and
      estimated hearing level using auditory brainstem response (ABR) recordings and
      the otoacoustic emission (OAE) test. RESULTS: ABR threshold value and DPOAE level
      showed that MSCs transplantation groups was improved than the SNHL group. And the
      number of spiral ganglion neurons were increased in all turn of the cochlea. And
      there was no evidence of acute immunological rejection and inflammation response
      was not observed. DISCUSSION: This study is to evaluate regenerative efficacy of
      hearing loss by transplanting mesenchymal stromal cells (MSCs) derived from human
      placenta (amnion and chorion) in deaf animal model. We identified that MSCs
      transplantation restored auditory impairment and promoted cell regeneration. We
      hope to overcome sensorineural hearing loss by transplanting stem cells such as
      mesenchymal stromal cells (MSCs) from easily accessible adult stem cell source in
      placenta.

PMID- 27863647
TI  - A tonsillectomy increased the risk of chronic rhinosinusitis among children: A
      three-year follow-up study.
AB  - OBJECTIVES: The study aimed to estimate the risk of developing chronic
      rhinosinusitis (CRS) among children who had undergone a tonsillectomy by
      utilizing a cohort study based on a population-based database. METHODS: Data for
      this retrospective cohort study were sourced from the Taiwan "Longitudinal Health
      Insurance Database 2000". We included 202 children who had undergone a
      tonsillectomy as the study group and 2020 sex- and age-matched children as the
      comparison group. We used stratified Cox proportional hazard regressions to
      calculate the hazard ratio (HR) and its corresponding 95% confidence interval
      (CI) for CRS during the 3-year follow-up period. RESULTS: Of 2222 sampled
      children, the incidence rate of CRS during the 3-year follow-up period was 3.2
      (95% CI = 2.0-4.8) 1000 person-years; 18.2 (95% CI = 9.1-32.5) per 1000 person
      years and 1.7 (95% CI = 0.8-3.0) per 1000 person-years for the study and
      comparison group, respectively. The stratified Cox proportional analysis showed
      that the adjusted hazard ratio for CRS during the 3-year follow-up period was
      8.28 (95% CI = 3.24-21.16) for children who had undergone a tonsillectomy than
      comparison patients. CONCLUSIONS: We demonstrated that the risk of developing CRS
      is significantly increased among children who have undergone a tonsillectomy.

PMID- 27863648
TI  - Biodegradable airway stents in infants - Potential life-threatening pitfalls.
AB  - OBJECTIVE: The solution of severe tracheobronchial obstructions in early
      childhood means a great challenge. Biodegradable stents were intended to be a
      minimally invasive temporary solution which may decrease the number of
      interventions and limit the possible complications of stenting procedures.
      However, our first experiences have brought out a new, - especially in childhood 
      potentially life-threatening complication of this concept. METHODS: Five SX-ELLA
      biodegradable polydioxanone stents was applied in three patients because of
      severe tracheobronchial obstruction: congenital tracheomalacia (7 day-old),
      acquired tracheomalacia (10 month-old), and congenital trachea-bronchomalacia (10
      month-old). RESULTS: The breathing of all children improved right after the
      procedure. We observed degradation of the stent from the 5th postoperative week
      which resulted in large intraluminar fragments causing significant airway
      obstruction: one patient died of severe pneumonia, the other baby required urgent
      bronchoscopy to remove the obstructing 'foreign body' from the trachea. In the
      third case repeated stent placements successfully maintained the tracheal lumen.
      CONCLUSIONS: Polydioxanone stents may offer an alternative to metallic or
      silastic stents for collapse or external compression of the trachea in children;
      however, large decaying fragments mean a potential risk especially in the small
      size pediatric airway. The fragmentation of the stent, which generally starts in
      the 4-6 postoperative weeks, may create large sharp pieces. These may be anchored
      to the mucosa and covered by crust leading to obstruction. As repeated
      interventions are required, we do not consider the application of biodegradable
      stents unambiguously advantageous.

PMID- 27863649
TI  - The universal newborn hearing screening program in a public hospital: The
      importance of the day of examination.
AB  - OBJECTIVES: Newborn hearing screening programs are already implemented in many
      countries worldwide. Nonetheless there is still no consensus about the most
      proper post-birth day of examination. The purpose of this study was to assess the
      most appropriate day of universal hearing screening program in a public hospital.
      MATERIAL AND METHODS: A prospective cohort study was conducted in "Attiko
      University National Health System Hospital" and included 2494 newborns. They were
      examined before discharge from the hospital, using transient evoked otoacoustic
      emissions (TEOAEs). RESULTS: From 2494 neonates included in the study, 2129
      (85.4%) bilaterally passed the screening examination, while 365 (14.6%) failed
      the test. Higher levels of "pass" result per day of life were presented the third
      (90%) and fourth (94%) day of life. These days the referral scores were lower,
      reaching 6% the 4th post-birth day. CONCLUSION: All infants should be screened
      for their hearing in the first days of life as otoacoustic emissions can be
      recorded from the first 24 h of life. If the babies stay in the maternity unit
      for more that 1-2 days for any reason (protocol of the maternity unit, parents
      leave in remote areas, etc.) we recommend the 4th day of life as the most
      appropriate day of examination in order to minimize the false positive ("refer")
      results at the initial examination.

PMID- 27863650
TI  - Perioperative considerations and complications in pediatric parathyroidectomy.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate perioperative considerations and post
      operative complications associated with parathyroidectomy in the pediatric
      population. METHODS: The Kids' Inpatient Database 21 (KID) was searched for
      patients who underwent parathyroidectomy in 2009 and 2012. Patient demographics,
      hospital stay, associated charges, and post-operative adverse sequelae were
      evaluated in all patients and included patient comorbidity and additional
      procedure requirement analysis. RESULTS: There were 182 patients extrapolating to
      262 parathyroidectomies over the two years analyzed. Although a minority of
      patients were male (45.4%), these patients had greater rates of complications,
      length of stay, and hospital charges. Importantly, minorities and younger
      patients (<=15y) also had more complicated post-operative courses. The lengths of
      stay for patients experiencing post-operative altered mental status (18.7d), post
      operative infection (15.5d), respiratory complications (19d), and cardiac
      complications (13d) were significantly increased compared to individuals without
      major complications (3.4d) (p < 0.001). Patients with pre-existing chronic kidney
      disease, dialysis-dependence, and bone sequelae (most commonly from hungry bone
      syndrome) also had significantly lengthier stays and greater associated costs.
      CONCLUSION: Findings from this analysis can be included in a comprehensive pre
      operative informed consent process between physicians and patients discussing
      perioperative considerations and potential complications of parathyroidectomy.
      Males, younger children, and patients with preexisting renal conditions
      experienced lengthier and more complicated hospital stays, suggesting the need
      for closer monitoring of these cohorts.

PMID- 27863651
TI  - Professor Alexander T. Florence: An exceptional scientist and man.

PMID- 27863652
TI  - Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine
      metastatic lung cancer model.
AB  - We have investigated the impact of hyaluronic acid (HA)-coating on the targeting
      capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake
      and localization of HA-lipoplexes were evaluated by flow cytometry and
      fluorescence microscopy and both methods showed that these lipoplexes were
      rapidly internalized and localized primarily within the cytoplasm. Inhibition of
      luciferase expression on the A549-luciferase lung cancer cell line was achieved
      in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition
      was obtained in vitro with HA-lipoplexes at +/- ratio 2. In vivo, in a murine
      A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti
      luciferase siRNA led to a statistically significant decrease of luciferase
      expression as opposed to progressive increase with non-modified lipoplexes or
      NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice
      treated with HA-lipoplexes supported the inhibition effect due to siRNA. These
      results highlight the potential of HA-lipoplexes in CD44-targeting siRNA
      delivery.

PMID- 27863653
TI  - Pharmacy preparations: Back in the limelight? Pharmacists make up your mind!
AB  - In this contribution to the theme issue recognizing prof. Florence's achievements
      as editor -in-chief of the Int. J. Pharmaceutics, we analyze the future of
      pharmacy preparations (also known as extemporaneous preparations or compounded
      products). Pharmacy preparations, long considered as an endangered part of the
      pharmacy profession on its way to extinction, may be at the brink of a revival.
      Drivers of this revival are a set of changes related to new clinical concepts and
      supply shortages. Moreover, new production and IT paradigms are being developed
      that facilitate the preparation processes and provide the necessary quality
      management systems. Finally, more detailed legislation (EU) and guidelines (US)
      gets a better hold on preparation in pharmacies. The question is now: is the
      pharmacy profession willing to accept preparation of high quality medicines in
      the pharmacy as an integral part of its professional tasks? If so, institutions
      for pharmacy education should provide the required competences to the pharmacy
      student. If not, alternative scenarios with other disciplines taking the lead
      should be considered. Whatever the choice made, the 'Physicochemical principles
      of pharmacy: in manufacture, formulation and clinical use' by Florence and
      Attwood (2016); will be on the engineer/pharmacy student's desk.

PMID- 27863654
TI  - High systemic availability of core-crosslinked polymeric micelles after
      subcutaneous administration.
AB  - Covalent entrapment of drug molecules within core-crosslinked polymeric micelles
      (CCPM) represents an attractive approach to improve their therapeutic index. As
      an alternative to the most commonly employed intravenous (i.v.) route,
      subcutaneous (s.c.) administration offers the possibility of self-administration
      and thereby may reduce healthcare costs. The aim of this work was to assess the
      pharmacokinetic profile and systemic availability of drug-containing CCPM
      following s.c. injection. We here derivatised dexamethasone (DMS) with three
      different linkers, which enabled covalent attachment of this drug to the core of
      CCPM. The obtained DMS-containing CCPM exhibited varying drug release kinetics in
      vitro. Remarkably, a single dose of DMS-containing CCPM resulted in high systemic
      availability of about 30% following s.c. injection into the flank of healthy
      mice, as evidenced by an AUC between 26-37% relative to the AUC attained
      following i.v. injection. Although different linkers resulted in moderate
      variations in pharmacokinetic parameters, the overall pharmacokinetic profiles of
      these i.v. or s.c. administered nanomedicines were not substantially different.
      Next to DMS, we covalently attached paclitaxel (PTX) to the core of CCPM.
      Similarly, a single s.c. dose of PTX-containing CCPM resulted in high systemic
      availability of about 40% compared to i.v. injection and PTX (entrapped plus
      released) was detected in the blood for at least 3days. Importantly, the systemic
      availability of s.c. administered drug-containing CCPM is substantially higher
      than that of other nanoformulations as reported in the literature (e.g. 3% in
      rodents). These results demonstrate that s.c. administration is a promising route
      to attain high systemic availability of CCPM, enabling a potentially more patient
      friendly and cost-effective treatment approach than the i.v. route.

PMID- 27863655
TI  - Direct in vivo evidence on the mechanism by which nanoparticles facilitate the
      absorption of a water insoluble, P-gp substrate.
AB  - Here we examine the mechanisms by which nanoparticles enable the oral absorption
      of water-insoluble, P-glycoprotein efflux pump (P-gp) substrates, without
      recourse to P-gp inhibitors. Both 200nm paclitaxel N-(2-phenoxyacetyl)-6-O
      glycolchitosan (GCPh) nanoparticles (GCPh-PTX) and a simulated Taxol formulation,
      facilitate drug dissolution in biorelevant media, unlike paclitaxel nanocrystals.
      Verapamil (40mgkg-1) increased the oral absorption from low dose Taxol (6 or
      10mgkg-1) by 100%, whereas the oral absorption from high dose Taxol (20mgkg-1) or
      low dose GCPh-PTX (6 or 10mgkg-1) was largely unchanged by verapamil. There was
      virtually no absorption from control paclitaxel nanocrystals (20mgkg-1). Imaging
      of ex-vivo rat ileum samples showed that fluorescently labelled GCPh
      nanoparticles are mucoadhesive and are taken up by ileum epithelial cells. GCPh
      nanoparticles were also found to open Caco-2 cell tight junctions. In conclusion,
      mucoadhesive, drug solubilising GCPh nanoparticles enable the oral absorption of
      paclitaxel via the saturation of the P-gp pump (by high local drug
      concentrations) and by particle uptake and tight junction opening mechanisms.

PMID- 27863656
TI  - Engineering thermosensitive liposome-nanoparticle hybrids loaded with doxorubicin
      for heat-triggered drug release.
AB  - The engineering of responsive multifunctional delivery systems that combine
      therapeutic and diagnostic (theranostic) capabilities holds great promise and
      interest. We describe the design of thermosensitive liposome-nanoparticle (NP)
      hybrids that can modulate drug release in response to external heating stimulus.
      These hybrid systems were successfully engineered by the incorporation of gold,
      silver, and iron oxide NPs into the lipid bilayer of lysolipid-containing
      thermosensitive liposomes (LTSL). Structural characterization of LTSL-NP hybrids
      using cryo-EM and AFM revealed the incorporation of metallic NPs into the lipid
      membranes without compromising doxorubicin loading and retention capability. The
      presence of metallic NPs in the lipid bilayer reinforced bilayer retention and
      offered a nanoparticle concentration-dependent modulation of drug release in
      response to external heating. In conclusion, LTSL-NP hybrids represent a
      promising versatile platform based on LTSL liposomes that could further utilize
      the properties of the embedded NPs for multifunctional theranostic applications.

PMID- 27863657
TI  - Development and characterization of polo-like kinase 2 loaded nanoparticles-A
      novel strategy for (serine-129) phosphorylation of alpha-synuclein.
AB  - Polo like kinase 2 (PLK2), a serine/threonine serum inducible kinase, has been
      proposed to be the major factor responsible for phosphorylating alpha-synuclein
      (alpha-syn) at Serine-129 (Ser-129) in Parkinson's disease (PD). A suitable
      strategy to gain insights into PLK2's biological effects might be to increase
      PLK2 intracellular levels with the aim of reproducing the slow progressive
      neuronal changes that occur in PD. The goal of this study was to develop and
      characterize a novel drug delivery system (DDS) for PLK2 cytosolic delivery using
      Total recirculating one machine system (TROMS), a technique capable of
      encapsulating fragile molecules while maintaining their native properties. A
      protocol for nanoparticle (NP) preparation using TROMS was set up. NPs showed a
      mean diameter of 257+/-15.61nm and zeta potential of -16+/-2mV, suitable for cell
      internalization. TEM and SEM images showed individual, spherical, dispersed NPs.
      The drug entrapment efficacy was 61.86+/-3.9%. PLK2-NPs were able to enter SH
      SY5Y cells and phosphorylate alpha-syn at Ser-129, demonstrating that the enzyme
      retained its activity after the NP manufacturing process. This is the first study
      to develop a DDS for continuous intracellular delivery of PLK2. These promising
      results indicate that this novel nanotechnology approach could be used to
      elucidate the biological effects of PLK2 on dopaminergic neurons.

PMID- 27863658
TI  - Regulatory aspects in the pharmaceutical development of nanoparticle drug
      delivery systems designed to cross the intestinal epithelium and M-cells.
AB  - This article reviews the field of oral uptake of nanoparticles across the
      gastrointestinal epithelium for the period 2006-2016. Analysis is conducted from
      the viewpoint of i) M-cell genetics and model development, ii) drug targeting to
      Peyer's patches and M-cells, and iii) physicochemical interactions of
      nanoparticles in the intestinal milieu. In light of these recent developments,
      regulatory considerations in the development of orally-absorbable nanoparticle
      drug products are discussed and focused on Module 3.2.P sub-sections of the
      Common Technical Document. Particular attention is paid to novel excipients,
      ligands and the non-standard method of manufacture. The novelty of this drug
      delivery system demands not only a multi-disciplinary scientific and regulatory
      approach but also a risk-adjusted consideration for a system defined by both
      processes and specifications. Given the current state of scientific development
      in the field it is suggested (in the author's personal opinion) that the design
      of nanoparticulate drug delivery systems should be kept as simple as possible
      (from a regulatory and manufacturing perspective) and to target the entire
      gastrointestinal epithelium.

PMID- 27863659
TI  - Docetaxel-loaded liposomes: The effect of lipid composition and purification on
      drug encapsulation and in vitro toxicity.
AB  - Docetaxel (DTX)-loaded liposomes have been formulated to overcome DTX solubility
      issue, improve its efficacy and reduce its toxicity. This study investigated the
      effect of steric stabilisation, varying liposome composition, and lipid:drug
      molar ratio on drug loading and on the physicochemical properties of the DTX
      loaded liposomes. Size exclusion chromatography (SEC) was used to remove free DTX
      from the liposomal formulation, and its impact on drug loading and in vitro
      cytotoxicity was also evaluated. Liposomes composed of fluid, unsaturated lipid
      (DOPC:Chol:DSPE-PEG2000) showed the highest DTX loading compared to rigid,
      saturated lipids (DPPC:Chol:DSPE-PEG2000 and DSPC:Chol:DSPE-PEG2000). The
      inclusion of PEG showed a minimum effect on DTX encapsulation. Decreasing
      lipid:drug molar ratio from 40:1 to 5:1 led to an improvement in the loading
      capacities of DOPC-based liposomes only. Up to 3.6-fold decrease in drug loading
      was observed after liposome purification, likely due to the loss of adsorbed and
      loosely entrapped DTX in the SEC column. Our in vitro toxicity results in PC3
      monolayer showed that non-purified, DTX-loaded DOPC:Chol liposomes were initially
      (24h) more potent than the purified ones, due to the fast action of the surface-
      adsorbed drug. However, we hypothesize that over time (48 and 72h) the purified,
      DTX-loaded DOPC:Chol liposomes became more toxic due to high intracellular
      release of encapsulated DTX. Finally, our cytotoxicity results in PC3 spheroids
      showed the superior activity of DTX-loaded liposomes compared to free DTX, which
      could overcome the DTX poor tissue penetration, drug resistance, and improve its
      therapeutic efficacy following systemic administration.

PMID- 27863660
TI  - Microfluidics based manufacture of liposomes simultaneously entrapping
      hydrophilic and lipophilic drugs.
AB  - Despite the substantial body of research investigating the use of liposomes,
      niosomes and other bilayer vesicles for drug delivery, the translation of these
      systems into licensed products remains limited. Indeed, recent shortages in the
      supply of liposomal products demonstrate the need for new scalable production
      methods for liposomes. Therefore, the aim of our research has been to consider
      the application of microfluidics in the manufacture of liposomes containing
      either or both a water soluble and a lipid soluble drug to promote co-delivery of
      drugs. For the first time, we demonstrate the entrapment of a hydrophilic and a
      lipophilic drug (metformin and glipizide respectively) both individually, and in
      combination, using a scalable microfluidics manufacturing system. In terms of the
      operating parameters, the choice of solvents, lipid concentration and
      aqueous:solvent ratio all impact on liposome size with vesicle diameter ranging
      from ~90 to 300nm. In terms of drug loading, microfluidics production promoted
      high loading within ~100nm vesicles for both the water soluble drug (20-25% of
      initial amount added) and the bilayer embedded drug (40-42% of initial amount
      added) with co-loading of the drugs making no impact on entrapment efficacy.
      However, co-loading of glipizide and metformin within the same liposome
      formulation did impact on the drug release profiles; in both instances the
      presence of both drugs in the one formulation promoted faster (up to 2 fold)
      release compared to liposomes containing a single drug alone. Overall, these
      results demonstrate the application of microfluidics to prepare liposomal systems
      incorporating either or both an aqueous soluble drug and a bilayer loaded drug.

PMID- 27863661
TI  - Doxorubicin enhances curcumin's cytotoxicity in human prostate cancer cells in
      vitro by enhancing its cellular uptake.
AB  - Doxorubicin (DOX) is a widely used drug in cancer treatment. Despite its
      popularity, it suffers from systemic side effects and susceptibility to drug
      resistance. Curcumin (CURC), on the other hand, is a drug that recently gained
      popularity due to its wide range of biological activities, including anti
      inflammatory and anti-cancer activities. Limitations to its clinical translation
      include its poor water solubility and the need for administration of high doses.
      Combinatory anti-cancer therapy has been proposed as a common approach to
      overcome one or more of these challenges. In this work, we propose a combinatory
      DOX and CURC anti-cancer therapy of prostate cancer cells in vitro. DOX and CURC
      were administered in the free drug and nanocapsule form, respectively. Cell size
      and complexity, cytotoxicity and apoptosis were studied by flow cytometry, MTT
      assay and sub-G1 quantification, respectively. Cellular uptake of CURC
      nanocapsules (CURC NCs) was quantified by fluorescence microscopy and high
      performance liquid chromatography fluorescence detection. Results showed that in
      vitro treatment with CURC NCs in the presence of subtherapeutic concentrations of
      DOX, led to significant increase in prostate cancer cells (PC3) apoptosis and
      death. This was likely due to significantly enhanced CURC uptake by the cells.
      The study presents a good rationale for pursuing combinatory CURC/DOX therapy in
      pre-clinical tumor animal models in the near future.

PMID- 27863662
TI  - Surface-assembled poly(I:C) on PEGylated PLGA microspheres as vaccine adjuvant:
      APC activation and bystander cell stimulation.
AB  - Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres are potential
      vehicles to deliver antigens for vaccination. Because they lack the full capacity
      to activate professional antigen presenting cells (APCs), combination with an
      immunostimulatory adjuvant may be considered. A candidate is the synthetic TLR3
      ligand polyriboinosinic acid-polyribocytidylic acid, poly(I:C), which drives cell
      mediated immunity. However, poly(I:C) has also been linked to the pathogenesis of
      autoimmunity, as affected by widespread stimulation of non-hematopoietic
      bystander cells. To address this aspect, we propose to minimize the poly(I:C)
      dose as well as to control the stimulation of non-immune bystander cells by
      poly(I:C). To facilitate the maturation of APCs with minimal poly(I:C) doses, we
      surface-assembled poly(I:C) onto PLGA microspheres. The microspheres' surface was
      further modified by poly(ethylene glycol) (PEG) coronas with varying PEG
      densities. PLGA microspheres loaded with tetanus toxoid (tt) as model antigen
      were manufactured by microextrusion-based solvent extraction. The negatively
      charged PLGA(tt) microspheres were coated with polycationic poly(l-lysine) (PLL)
      polymers, either PLL itself or PEG-grafted PLL (PLL-g-PEG) with varying grafting
      ratios (g=2.2 and g=10.1). Stable surface assembly of poly(I:C) was achieved by
      subsequent incubation of polymer-coated PLGA microspheres with aqueous poly(I:C)
      solutions. We evaluated the immunostimulatory potential of such PLGA(tt)
      microsphere formulations on monocyte-derived dendritic cells (MoDCs) as well as
      human foreskin fibroblasts (HFFs) as model for non-hematopoietic bystander cells.
      Formulations with surface-assembled poly(I:C) readily activated MoDCs with
      respect to the expression of maturation-related surface markers, proinflammatory
      cytokine secretion and directed migration. When surface-assembled, poly(I:C)
      enhanced its immunostimulatory activity by more than one order of magnitude as
      compared to free poly(I:C). On fibroblasts, surface-assembled poly(I:C)
      upregulated class I MHC but not class II MHC. Phagocytosis of PLGA(tt)
      microsphere formulations by MoDCs and HFFs remained mostly unaffected by PEG
      grafted PLL coatings. In contrast, high concentrations of free poly(I:C) led to a
      marked drop of microsphere phagocytosis by HFFs. Overall, surface assembly on
      PEGylated PLGA microspheres holds promise to improve both efficacy and safety of
      poly(I:C) as vaccine adjuvant.

PMID- 27863663
TI  - Preparation of theophylline inhalable microcomposite particles by wet milling and
      spray drying: The influence of mannitol as a co-milling agent.
AB  - Inhalable theophylline particles with various amounts of mannitol were prepared
      by combining wet milling in isopropanol followed by spray drying. The effect of
      mannitol as a co-milling agent on the micromeritic properties, solid state and
      aerosol performance of the engineered particles was investigated. Crystal
      morphology modelling and geometric lattice matching calculations were employed to
      gain insight into the intermolecular interactions that may influence the
      mechanical properties of theophylline and mannitol. The addition of mannitol
      facilitated the size reduction of the needle-like crystals of theophylline and
      also their assembly in microcomposites by forming a porous structure of mannitol
      nanocrystals wherein theophylline particles are embedded. The microcomposites
      were found to be in the same crystalline state as the starting material(s)
      ensuring their long-term physical stability upon storage. Incorporation of
      mannitol resulted in microcomposite particles with smaller size, more spherical
      shape and increased porosity. The aerosol performance of the microcomposites was
      markedly enhanced compared to the spray-dried suspension of theophylline wet
      milled without mannitol. Overall, wet co-milling with mannitol in an organic
      solvent followed by spray drying may be used as a formulation approach for
      producing respirable particles of water-soluble drugs or drugs that are prone to
      crystal transformation in an aqueous environment (i.e. formation of hydrates).

PMID- 27863664
TI  - Optimized synthesis and crystalline stability of gamma-cyclodextrin metal-organic
      frameworks for drug adsorption.
AB  - The biocompatible and renewable cyclodextrin metal-organic frameworks (CD-MOFs)
      have addressed a range of opportunities in molecular storage and separation
      sciences. The reported protocols for their synthesis, however, were carried out
      at room temperature over long time periods of time (24h), producing crystals of
      relatively poor uniformity. In this investigation, micron sized gamma-CD-MOFs
      were synthesized by an optimized vapor diffusion method at elevated temperature
      (50 degrees C) within 6h, after which the size control, crystalline stability and
      drug adsorption behavior were investigated in detail. In this manner, uniform
      cubic gamma-CD-MOF crystals were obtained when the reaction temperature was
      raised to 50 degrees C with pre-addition of the reaction solvent. The size of
      gamma-CD-MOFs was adjusted efficiently by changing the reactant concentrations,
      temperatures, time, gamma-CD ratios to KOH and surfactant concentrations, without
      influencing the porosity and crystallinity of the material markedly. Varing
      degrees of reduction in crystallinity and change in morphology were observed when
      the gamma-CD-MOF crystals are treated under conditions of high temperature (100
      degrees C), high humidity (92.5%) and polar solvents (e.g., MeOH and DMF). In
      relation to drug adsorption by gamma-CD-MOFs, most of the drug molecules
      containing carboxyl groups showed relatively high adsorption (>5%), while low
      adsorption (<5%) was found for drugs with nitrogen-containing heterocyclic rings.
      In addition, the adsorption kinetics of captopril to standard gamma-CD-MOFs
      matched a pseudo-second-order model rather well, whilst captopril adsorption to
      the damaged gamma-CD-MOFs only partially matched the pseudo-second-order model.
      In summary, based upon the optimized synthesis and size control of gamma-CD-MOFs,
      the crystalline stability and drug adsorption characteristics of gamma-CD-MOF
      crystals have been evaluated as a fundamental requirement of a potential vehicle
      for drug delivery.

PMID- 27863665
TI  - Biodegradable hydrophilic carriers for the oral delivery of hematological factor
      IX for hemophilia B treatment.
AB  - Current protein replacement therapies for hemophilia B, a genetic bleeding
      disorder caused by a deficiency in coagulation factor IX, rely on IV injections
      and infusions. Oral delivery of factor IX is a desirable needle-free option,
      especially for prophylaxis. We have developed a biodegradable, pH-responsive
      hydrogel microcarrier system based on the poly(methacrylic acid)-grafted
      poly(ethylene glycol) [P(MAA-g-EG)]. Incorporation of an enzymatically degradable
      peptide crosslinking agent allows for site-specific degradation by trypsin in the
      small intestine. P(MAA-g-EG) polymer was synthesized by UV polymerization, and
      then subsequently crosslinked with peptide crosslinking agent using EDC-NHS
      chemistry. Physical characterization included FTIR for determining the
      composition of the peptide crosslinked polymer and SEM for microparticle
      morphology. The pH-responsive swelling and enzyme-specific degradation were
      confirmed by bright-field microscopy and the corresponding kinetics were
      determined by turbidimetric measurements. Evaluating the drug delivery
      application of this degradable system, factor IX release studies showed site
      specific release, and in vitro transport studies resulted in improved factor IX
      absorption. Incorporation of the degradable crosslinking agent significantly
      improved the delivery potential as compared to previously reported non-degradable
      drug delivery systems. Using this degradable P(MAA-g-EG) system as a delivery
      vehicle for factor IX can possibly lead to an orally administered prophylactic
      treatment for hemophilia B patients.

PMID- 27863666
TI  - Nasal powders of thalidomide for local treatment of nose bleeding in persons
      affected by hereditary hemorrhagic telangiectasia.
AB  - In this work nasal powder formulations of thalidomide were designed and studied
      to be used by persons affected by hereditary hemorrhagic telangiectasia as a
      complementary anti-epistaxis therapy, with the goal of sustaining the effect
      obtained with thalidomide oral treatment after its discontinuation for adverse
      effects. Three nasal powders were prepared using as carriers beta-CD or its more
      hydrophilic derivatives such as hydropropyl-beta-CD and sulphobutylether-beta-CD
      and tested with respect to technological and biopharmaceutical features after
      emission with active and passive nasal powder devices. For all formulated
      powders, improved dissolution rate was found compared to that of the raw
      material, making thalidomide promptly available in the nasal environment at a
      concentration favouring an accumulation in the mucosa. The very limited
      transmucosal transport measured in vitro suggests a low likelihood of significant
      systemic absorption. The topical action on bleeding could benefit from the poor
      absorption and from the fact that about 2-3% of the thalidomide applied on the
      nasal mucosa was accumulated within the tissue, particularly with the beta-CD
      nasal powder.

PMID- 27863667
TI  - Ibuprofen delivery into and through the skin from novel oxidized cellulose-based
      gels and conventional topical formulations.
AB  - The delivery of ibuprofen into and through the skin from novel formulations
      containing TEMPO-oxidized cellulose nanofibril-based (TOCN) gels was compared to
      that from two conventional and commercially available products. The gels were
      evaluated in-vitro (using both silicone membranes, and pig skin) and in-vivo in
      human volunteers. All gels showed consistent behaviour in a standard in vitro
      release test. The stratum corneum (SC) uptake and skin penetration of ibuprofen
      in vitro from the novel gels and the marketed formulations were generally
      comparable even though the drug loading in the TOCN-based vehicles was only 20%
      of that in the 'reference' products. In vivo, the new gels appeared to enhance
      drug uptake into the SC following a relatively short application time, again
      matching the performance of the commercial formulations. Taken together, the
      results of this research provide proof-of-concept for the idea that the
      sustainable, oxidized cellulose gels may provide more efficient drug delivery
      into and through the skin, thereby improving drug utilisation and reducing
      potential adverse effects when such formulations are applied chronically over
      large skin areas.

PMID- 27863668
TI  - Nanotechnologies for the treatment of colon cancer: From old drugs to new hope.
AB  - Colorectal cancer is a wide-reaching health problem due to its incidence and to
      the high mortality rates. Adjuvant chemotherapies have considerably improved the
      prognosis and/or the overall survival of patients with locally advanced and
      metastatic cancers. Nevertheless, their efficiency remains limited due to
      intrinsic and emerging multidrug resistance (MDR) of cancer cells, and to major
      adverse effects and dose limiting toxicities. The present review discusses the
      knowledge of clinically relevant mechanisms of resistance to cytotoxic and
      targeted therapies for the treatment of colorectal cancer, and focuses on the
      benefit of nanomedicine approach to circumvent these processes. Nanomedicaments
      should allow extensive cancer cell drug loading independent on cell surface
      transporters, -thus overwhelming drug metabolism and efflux-, but also alleviate
      side-effects related to tissue-dependent drug uptake. Finally, we provide an
      outline of preclinical and clinical studies of nanoparticles formulations for
      colorectal cancer treatment, and briefly discuss strategies to optimize the
      selective delivery of these nanomedicines to colorectal cancer cells.

PMID- 27863669
TI  - UV-curable gels as topical nail medicines:In vivo residence, anti-fungal efficacy
      and influence of gel components on their properties.
AB  - UV-curable gels, used as nail cosmetics for their in vivo durability, were
      reported to be promising as topical nail medicines. Our first aim was thus to
      investigate whether such durability applies to drug-loaded formulations. This was
      found to be true. However, ethanol inclusion in the pharmaceutical formulation
      (to enable drug loading) reduced the in vivo residence. The second aim was
      therefore to determine any other effects of ethanol, and if ethanol could be
      avoided by the choice of monomers. Thus, three methacrylate monomers, ethyl
      methacrylate, isobornyl methacrylate and 2-hydroxyethyl methacrylate (HEMA) were
      selected, and their influence on the formulation properties were determined.
      Ethanol and the methacrylate monomer influenced some (but not all) of the
      formulation properties. The most significant was that HEMA could dissolve drug
      and enable the preparation of ethanol-free, drug-loaded formulations, which would
      benefit in vivo residence. The absence of ethanol reduced drug loading, release
      and ungual flux, but had no negative impact on the in vitro anti-fungal efficacy.
      Thus, judicious selection of gel components enabled the exclusion of ethanol. The
      long in vivo residence, little residual monomers, sufficient ungual permeation
      and in vitro anti-fungal activity of the gels indicates their potential as anti
      onychomycotic topical medicines.

PMID- 27863670
TI  - Selection and fabrication of a non-woven polycarbonate urethane cover for a
      tissue engineered airway stent.
AB  - One of the major problems in end-stage bronchotracheal cancer is stenosis of the
      upper airways, either due to luminal ingrowth of the tumor or mucus plugging.
      Airway stents that suppress tumor ingrowth and sustain mucociliary transport can
      alleviate these problems in end-stage bronchial cancer. We evaluated different
      types of polymeric covers for a tissue engineered airway stent. The
      distinguishing feature of this stent concept is that respiratory epithelial cells
      can grow on the luminal surface of the stent which facilitates mucociliary
      clearance. To facilitate growth of epithelial cells at the air-liquid interface
      of the stent, we developed a polyurethane cover that allows transport of
      nutrients to the cells. Nonwoven polycarbonate urethane (PCU) covers were
      prepared by a spraying process and evaluated for their porosity and glucose
      permeability. Respiratory epithelial cells harvested from sheep trachea were
      cultured onto the selected PCU cover and remained viable at the air-liquid
      interface when cultured for 21days. Lastly, we evaluated the radial force of a
      PCU-covered nitinol stent, and showed the PCU covers did not adversely affect the
      mechanical properties of the stents for their intended application in the smaller
      bronchi. These in vitro data corroborate the design of a novel airway stent for
      palliative treatment of bronchotracheal stenosis by combination of stent
      technology with tissue-engineered epithelial cells.

PMID- 27863671
TI  - Oral transmucosal delivery of naratriptan.
AB  - Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the
      treatment of migraine and is available in tablet dosage forms for oral
      administration. Buccal drug delivery offers a number of advantages compared with
      conventional oral delivery including rapid absorption, avoidance of first pass
      metabolism and improved patient compliance. We have previously prepared and
      characterised the base form of NAR and shown that it has more favourable
      properties for buccal delivery compared with NAR.HCl. This study describes the
      design and evaluation of a range of formulations for oral transmucosal delivery
      of NAR base. Permeation studies were conducted using excised porcine buccal
      tissue mounted in Franz cells. Of the neat solvents examined, Transcutol(r) P
      (TC) showed the greatest enhancement effects and was the vehicle in which NAR was
      most soluble. The mechanisms by which TC might promote permeation were further
      probed using binary systems containing TC with either buffer or Miglyol 812(r)
      (MG). Mass balance studies were also conducted for these systems. The permeation
      of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC
      appears to promote enhanced membrane permeation of NAR because of its rapid
      uptake into the buccal tissue. Synergistic enhancement of buccal permeation was
      observed when TC was combined with MG and this is attributed to the increased
      thermodynamic activity of NAR in these formulations. Significantly enhanced
      permeation of NAR was achieved for TC:MG and this was also associated with less
      TC remaining on the tissue or in the tissue at the end of the experiment. To our
      knowledge this is the first report where both enhancer and active have been
      monitored in buccal permeation studies. The findings underline the importance of
      understanding the fate of vehicle components for rational formulation design of
      buccal delivery systems.

PMID- 27863672
TI  - Hot melt extruded transdermal films based on amorphous solid dispersions in
      Eudragit RS PO: The inclusion of hydrophilic additives to develop moisture
      activated release systems.
AB  - A series of Eudragit RS PO-based hot melt extruded films were evaluated as
      potential transdermal systems, with particular emphasis on the inclusion of
      hydrophilic excipients to allow water sorption, which in turn would allow drug
      release on application to the skin. More specifically, sucrose, methyl cellulose,
      xanthan gum (Xantural(r)75), poloxamer (Pluronic(r)F127), Gelucire 44/14 were
      added to Eudragit RS PO and assessed in terms of physical structure (modulated
      temperature DSC (MTDSC), thermogravimetric analysis (TGA), powder XRD (PXRD),
      scanning electron microscopy(SEM)) and in vitro drug release and permeation
      properties. In addition, the effect of prior hydration on drug permeation was
      studied for selected systems. Phase separation was noted for sucrose,
      methylcellulose (high loading), xanthan gum (high loading), poloxamer and
      Gelucire 44/14 (high loading) using both visual observation and MTDSC. PXRD
      studies indicated drug crystallization within the phase separated systems. SEM
      studies broadly followed the same pattern. Dissolution studies indicated that the
      hydrophilic excipients considerably enhanced the release rate, while Franz
      diffusion cell studies showed a much greater variability in effectiveness, which
      we ascribe to the paucity of water of hydration present which would not allow
      swellable additives such as xanthan to release the drug. However, films
      containing Gelucire 44/14 emerged as the most satisfactory systems, despite the
      higher additive loaded systems showing drug phase separation. This may be related
      to emulsification rather than swelling on contact with water, as noted for the
      permeation studies involving pre-hydration. This strategy therefore presents a
      promising approach for triggered transdermal drug delivery, activated by
      hydration from the skin itself.

PMID- 27863673
TI  - Laser irradiation to produce amorphous pharmaceuticals.
AB  - Using a high-power CO2 laser to irradiate powder beds, it was possible to induce
      phase transformation to the amorphous state. Irradiation of a model drug,
      indometacin, resulted in formation of a glass. Varying the settings of the laser
      (power and raster speed) was shown to change the physicochemical properties of
      the glasses produced and all irradiated glasses were found to be more stable than
      a reference glass produced by melt-quenching. Irradiation of a powder blend of
      paracetamol and polyvinylpyrrolidone K30 was found to produce a solid amorphous
      dispersion. The results suggest that laser-irradiation might be a useful method
      for making amorphous pharmaceuticals.

PMID- 27863674
TI  - Fused-filament 3D printing of drug products: Microstructure analysis and drug
      release characteristics of PVA-based caplets.
AB  - Fused deposition modeling (FDM) 3-Dimensional (3D) printing is becoming an
      increasingly important technology in the pharmaceutical sciences, since it allows
      the manufacture of personalized oral dosage forms by deposition of thin layers of
      material. Here, a filament extruder was used to obtain filaments of polyvinyl
      alcohol (PVA) containing paracetamol or caffeine appropriate for 3D printing. The
      filaments were used to manufacture caplets for oral administration by FDM 3D
      printing, with the aim of evaluating the effect of the internal structure
      (micropore volume), drug loading and composition on drug dissolution behaviour.
      Micropore volume of the caplets was primarily determined by the presence of large
      pores due to gaps in the printed layers/net while printing, and the porosity of
      the caplets was 10 fold higher than the porosity of the extruded filament.
      Dynamic dissolution drug release tests on the caplets in biorelevant bicarbonate
      media revealed distinctive release profiles, which were dependent on drug
      solubility and drug loading. Porosity of the caplets did not help to predict the
      different drug release profiles. This study confirms the potential of 3D printing
      to fabricate caplets and helps to elucidate which factors influence drug release
      from this type of new dosage form.

PMID- 27863675
TI  - Age-appropriate and acceptable paediatric dosage forms: Insights into end-user
      perceptions, preferences and practices from the Children's Acceptability of Oral
      Formulations (CALF) Study.
AB  - A lack of evidence to guide the design of age-appropriate and acceptable dosage
      forms has been a longstanding knowledge gap in paediatric formulation
      development. The Children's Acceptability of Oral Formulations (CALF) study
      captured end-user perceptions and practices with a focus on solid oral dosage
      forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates
      (administered with food) and mini-tablets (administered directly into the mouth).
      A rigorous development and testing phase produced age-adapted questionnaires as
      measurement tools with strong evidence of validity and reliability. Overall, 590
      school children and adolescents, and 428 adult caregivers were surveyed across
      hospitals and various community settings. Attitudes towards dosage forms
      primarily differed based on age and prior use. Positive attitudes to tablets and
      capsules increased with age until around 14 years. Preference was seen for
      chewable and orodispersible preparations across ages, while multiparticulates
      were seemingly less favourable. Overall, 59.6% of school children reported
      willingness to take 10mm diameter tablets, although only 32.1% of caregivers
      perceived this size to be suitable. While not to be taken as prescriptive
      guidance, the results of this study provide some evidence towards rational dosage
      form design, as well as methodological approaches to help design tools for
      further evaluation of acceptability within paediatric studies.

PMID- 27863676
TI  - My dear friend Professor Alexander Taylor Florence the epitome of British humour
      and elegance, who has had a tremendous influence on the Japanese pharmaceutical
      community.

PMID- 27863677
TI  - An observational study of the effect of vibration on the caking of suspensions in
      oily vehicles.
AB  - An oily suspension of penethamate (PNT) that was physically stable on storage,
      caked solidly during road/air transport. This paper reports on the caking
      behaviour of PNT oily suspension formulations exposed to vibrations in a lab
      based test designed to simulate road/air transport. The lab-test was used to
      study the effects of container type (glass v PET) and formulation (oil,
      surfactant type and concentration) on the physical stability of suspension under
      vibration. Redispersibility of the sediment was lower at longer vibrations times
      and at higher intensity of vibration. Caking on vibration was strongly influenced
      by the type of container (caking in glass but not in PET) possibly due to tribo
      charging of particles. Caking on vibration was dependent on the formulation: type
      and concentration of surfactant; type of oil. The physical stability of oily
      suspensions, and the effect of vibration are two areas which have been largely
      neglected in the pharmaceutical literature. This paper discusses some potential
      mechanisms for the observations but studies using fully characterised materials
      are required. Finally we conclude that static testing of physical stability of
      oily suspensions is not sufficient and that a vibrational stress test is
      required.

PMID- 27863678
TI  - Formulation and characterization of a liquid crystalline hexagonal mesophase
      region of phosphatidylcholine, sorbitan monooleate, and tocopherol acetate for
      sustained delivery of leuprolide acetate.
AB  - Although liquid crystal (LC) systems have been studied before, their utility in
      drug delivery applications has not been explored in depth. This study examined
      the development of a 1-month sustained release formulation of leuprolide acetate
      using an in situ-forming LC matrix. The phase progression upon water absorption
      was tested through construction of ternary phase diagrams of phosphatidylcholine,
      sorbitan monooleate, and tocopherol acetate (TA) at increasing water content.
      Small angle X-ray scattering revealed the presence of lamellar and hexagonal
      mesophases. The physicochemical characteristics and in vitro drug release were
      evaluated as a function of the ternary component ratio and its resultant phase
      behavior. Formulations with increased water uptake capacity displayed greater
      drug release and enhanced erodability. Removal of TA resulted in increased water
      uptake capacity and drug release, where 8% (w/w) TA was determined as the
      critical concentration threshold for divergence of release profiles. In
      conclusion, characterization of the resultant HII mesophase region provided
      information of the impact the individual components have on the physicochemical
      properties and potential drug release mechanisms. This high mitigating impact of
      TA on drug release indicates the use of TA as a tailoring agent, broadening the
      therapeutic applications of this LC system.

PMID- 27863679
TI  - Effect of moisture sorption on the performance of crospovidone.
AB  - Crospovidone is a commonly used tablet disintegrant. However, the synthetic
      disintegrant has been known to be hygroscopic and high moisture content in
      crospovidone used could exert deleterious effects on tablets formulated with it.
      The objective of this study was to elicit a better understanding between
      crospovidone-water interaction and its effect on disintegrant performance.
      Moisture sorption and desorption isotherms were obtained together with the
      enthalpy of immersion. Crospovidone samples stored at four relative humidities
      were used to formulate tablets and the resultant tablets were evaluated for their
      mechanical, dimensional and disintegratability attributes. Analyses of the
      moisture sorption isotherms indicated that externally adsorbed moisture accounted
      for the bulk of the total moisture content in crospovidone, with minimal amount
      of moisture absorbed intramolecularly. Enthalpy of immersion became less
      exothermic with crospovidone samples stored at increasing storage humidity.
      Correspondingly, improvement in disintegration time became less pronounced. This
      was postulated to be a consequence of premature wetting of the particle surfaces
      by externally adsorbed moisture. High humidity was also detrimental to tablet
      hardness and thickness. In conclusion, the impact of moisture sorption during
      storage by excipients such as crospovidone could be better understood by the
      appreciation of crospovidone-water interaction and its consequence on tablet
      quality.

PMID- 27863680
TI  - In honor of Prof. A.T. Florence.

PMID- 27863682
TI  - Professor A.T. Florence: A towering figure in Pharmaceutics.

PMID- 27863681
TI  - Combinatorial nanodiamond in pharmaceutical and biomedical applications.
AB  - One of the newly emerging carbon materials, nanodiamond (ND), has been exploited
      for use in traditional electric materials and this has extended into biomedical
      and pharmaceutical applications. Recently, NDs have attained significant
      interests as a multifunctional and combinational drug delivery system. ND studies
      have provided insights into granting new potentials with their wide ranging
      surface chemistry, complex formation with biopolymers, and combination with
      biomolecules. The studies that have proved ND inertness, biocompatibility, and
      low toxicity have made NDs much more feasible for use in real in vivo
      applications. This review gives an understanding of NDs in biomedical engineering
      and pharmaceuticals, focusing on the classified introduction of ND/drug
      complexes. In addition, the diverse potential applications that can be obtained
      with chemical modification are presented.

PMID- 27863683
TI  - Thirty years with cyclodextrins.
AB  - This paper reviews the work carried out on cyclodextrins during some thirty years
      at the Institut Galien Paris-Sud, UMR CNRS 8612, Universite Paris-Sud. It
      represents the normal evolution of this domain of science and the numerous
      possibilities of cyclodextrins for being a tool adaptable to the most complex
      situations. The works which have been carried out concern: the investigation of
      general characteristics of cyclodextrins and derivatives, the preparation and
      evaluation of inclusion complexes, the use of cyclodextrins in the preparation of
      drug delivery systems, the various possibilities offered by cyclodextrins and
      their derivatives for nanoparticle preparation and finally the use of
      cyclodextrins for the preparation of biomaterials is evoked.

PMID- 27863684
TI  - Sandy Florence: The renaissance man.

PMID- 27863685
TI  - The gut in the beaker: Missing the surfactants?
AB  - Gastrointestinal drug administration is the preferred route for the majority of
      drugs however, the natural physiology and physicochemistry of the
      gastrointestinal tract is critical to absorption but complex and influenced by
      factors such as diet or disease. The pharmaceutical sciences drive for product
      consistency has led to the development of in vitro product performance tests
      whose utility and interpretation is hindered by the complexity, variability and a
      lack of understanding. This article explores some of these issues with respect to
      the drug, formulation and the presence of surfactant excipients and how these
      interact with the natural bile salt surfactants. Interactions start in the mouth
      and during swallowing but the stomach and small intestine present the major
      challenges related to drug dissolution, solubility, the impact of surfactants and
      supersaturation along with precipitation. The behaviour of lipid based
      formulations and the influence of surfactant excipients is explored along with
      the difficulties of translating in vitro results to in vivo performance. Possible
      future research areas are highlighted with the conclusion that, "a great deal of
      work using modern methods is still required to clarify the situation".

PMID- 27863686
TI  - Formulation design space for stable, pH sensitive crystalline nifedipine
      nanoparticles.
AB  - Enteric coated formulations protect drugs from degrading in the harsh environment
      of the stomach (acidic pH and enzymes), and promotes drug delivery to and
      absorption into the duodenum and/or later parts of the intestine. Four DoE models
      were applied to optimize formulation parameters for the preparation of pH
      sensitive nifedipine nanoparticles. Stability studies were performed on the
      optimized formulations to monitor any possible variation in particle size
      distribution, homogeneity index, surface charge and drug release (pH 1.2 and pH
      6.8). Stability studies were performed for 3 months at 4 degrees C, 25 degrees C
      and 40 degrees C. A combination of Eudragit(r)L 100-55 and polyvinyl alcohol was
      determined to be the most effective in stabilizing the nanoparticle suspension.
      The average particle size distribution, polydispersity index and surface charge
      of the optimized pH sensitive nifedipine nanoparticles were determined to be
      131.86+/-8.21nm, 0.135+/-0.008 and -7.631+/-0.146mV, respectively. Following
      three months storage, it was observed that the formulations stored at 4 degrees C
      were stable in terms of particle size distribution, polydispersity index, surface
      charge, drug loading and drug release, whereas those stored at 25 degrees C and
      40 degrees C were relatively unstable. A predictive model to prepare stable pH
      sensitive nifedipine nanoparticles, was successfully developed using multiple
      linear regression analysis.

PMID- 27863687
TI  - Sandy Florence, a man of many talents!

PMID- 27863688
TI  - Determination of the activity of maleimide-functionalized phospholipids during
      preparation of liposomes.
AB  - Numerous examples exist in the literature for the use of maleimide-thiol
      reactions in the area of functionalized nanoparticles. Although the hydrolysis
      tendency of maleimides is well-known, qualitative and quantitative information on
      the stability and reactivity of maleimide groups during preparation and in final
      formulations are missing. This is surprising, since hydrolysis of maleimides
      prevents nanoparticle functionalization and results in an increase of negative
      surface charge due to the hydrolysis product maleic acid. In this study we
      investigated the stability of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N
      [maleimide-2000] (DSPE-PEG2000-Mal) during the preparation of liposomes via two
      common preparation methods, which can be distinguished by the insertion of DSPE
      PEG2000-Mal during or after the liposome formation process (pre-insertion and
      post-insertion process). The liposomes prepared by the pre-insertion method had
      63% active maleimide groups remaining on their surface. The activity decreased
      dramatically during the purification process down to 32%. The preparation by post
      insertion showed minimal effects with regard to maleimide activity. 76% of
      maleimide groups were active and therefore available for coupling reaction. By
      identifying active maleimide groups on the surface of the final formulations, the
      presented work revealed the dramatic impact of preparation methods on the
      activity of maleimide groups.

PMID- 27863689
TI  - Endophthalmitis.

PMID- 27863690
TI  - Cocoon syndrome with hepatic involvement. Incidental finding during orthotopic
      liver transplantation.

PMID- 27863691
TI  - Atypical location of a glomus tumor in the liver.

PMID- 27863692
TI  - Intrahepatic Masson tumor (intravascular papillary endothelial hyperplasia).

PMID- 27863693
TI  - Surgical treatment of non-functioning pancreatic neuroendocrine tumours based on
      three clinical scenarios.
AB  - INTRODUCTION: The treatment of patients with non-functioning pancreatic
      neuroendocrine tumours (NFPNET) is resection in locally pancreatic disease, or
      with resectable liver metastases. There is controversy about unresectable liver
      disease. METHODS: We analysed the perioperative data and survival outcome of 63
      patients who underwent resection of NFPNET between 1993 and 2012. They were
      divided into 3 scenarios: A, pancreatic resection (44patients); B, pancreatic and
      liver resection in synchronous resectable liver metastases (12patients); and C,
      pancreatic resection in synchronous unresectable liver metastases (6patients).
      The prognostic factors for survival and recurrence were studied. RESULTS: Distal
      pancreatectomy (51%) and pancreaticoduodenectomy (38%) were more frequently
      performed. Associated surgery was required in 44% of patients, including
      synchronous liver resections in 9patients. Two patients received a liver
      transplant during follow-up. According to the WHO classification they were
      distributed into G1: 10 (16%), G2: 45 (71%), and G3: 8 (13%). The median hospital
      stay was 11days. Postoperative morbidity and mortality were 49% and 1.6%,
      respectively. At the closure of the study, 43 (68%) patients were still alive,
      with a mean actuarial survival of 9.6years. The WHO classification and tumour
      recurrence were risk factors of mortality in the multivariate analysis. The
      median actuarial survival by scenarios was 131months (A), 102months (B), and
      75months (C) without statistically significant differences. CONCLUSIONS: Surgical
      resection is the treatment for NFPNET without distant disease. Resectable liver
      metastases in well-differentiated tumours must be resected. The resection of the
      pancreatic tumour with unresectable synchronous liver metastasis must be
      considered in well-differentiated NFPNET. The WHO classification grade and
      recurrence are risk factors of long-term mortality.

PMID- 27863694
TI  - Titanium posts and bonded amalgam core longevity: A 22-year clinical survival
      retrospective study.
AB  - BACKGROUND: The authors conducted a retrospective study to evaluate the long-term
      (18-22 years) clinic results of titanium post and bonded amalgam core
      restorations with metal-ceramic crowns placed in patients. METHODS: From 1992
      through 1996, the authors placed 88 restorations in 66 patients. They measured
      the ferrule effect in the minor dentin collar area. In 2014, the authors analyzed
      the following variables: ferrule length, length and thickness of the post, and
      tooth position. RESULTS: The overall survival of the restorations decreased over
      time with survival rates of 89.6% after 5 years of follow-up appointments and
      64.2% after 18 years of follow-up appointments. There were 42 failures, and the
      maxillary premolars had the most failures. The teeth with 2 or more millimeters
      ferrule length had a higher survival rate than those with a 0 to less than 2 mm
      ferrule length; these results were not statistically significant. CONCLUSIONS:
      Statistically significant differences were detected according to the location of
      the tooth. The cores in the anterior teeth were 3.26 times more likely to fail
      than those in the molars, which presented higher survival rates; maxillary
      premolars had the most failures (28.5%). Both the metallic post length and its
      diameter did not influence restoration survival. The ferrule length was not
      statistically significant. PRACTICAL IMPLICATIONS: The clinical technique to
      restore endodontically treated teeth that includes a titanium post and bonded
      amalgam restorations results in greater coronal destruction but shows good long
      term results, ease of fabrication, and modest cost in comparison with other
      techniques.

PMID- 27863695
TI  - Analysis of a Low Dose Protocol to Reduce Patient Radiation Exposure During
      Percutaneous Coronary Interventions.
AB  - The cardiac catheterization laboratory is an important source of radiation for
      patients and operators and it is good practice to limit exposure as much as
      possible. The purpose of this study was to evaluate the effectiveness and impact
      of a radiological low dose protocol (LDP) in terms of reduction in patient
      radiation exposure during percutaneous coronary interventions (PCIs). From
      November 2014 to October 2015, 906 consecutive patients who underwent PCI were
      evaluated. Of these, 571 patients (63%) were treated with the standard dose
      protocol (SDP) of 15 frames per second for cine acquisition and standard settings
      for fluoroscopy, and 335 patients (37%) with the LDP of 7.5 frames per second for
      cine acquisition and low-dose settings for fluoroscopy. In the LDP group, we
      observed a significant reduction of kerma area product (53.3 LDP vs 115 SDP
      Gycm2, p <0.0001) and air kerma at interventional reference point (0.79 LDP vs
      1.976 SDP Gy, p <0.0001). Marked differences were observed regarding the
      exceeding of International Commission on Radiological Protection and National
      Council on Radiation Protection and Measurements' air kerma at interventional
      reference point trigger level (cutoff for potential skin injuries), which were
      significantly lower in the LDP group (1.8% vs 7.2%, p <0.0001). Such difference
      was more relevant in complex PCI. In conclusion, the implementation of LDP
      allowed a marked reduction in patient dosimetric parameters for PCI and
      significantly reduced the risk of exceeding the International Commission on
      Radiological Protection/National Council on Radiation Protection and Measurements
      trigger levels for potential skin injuries.

PMID- 27863696
TI  - A Discussion of Contemporary Nomenclature, Diagnosis, Imaging, and Management of
      Patients With Hypertrophic Cardiomyopathy.

PMID- 27863697
TI  - A new model for the study of neuropathic pain after brachial plexus injury.
AB  - The study was to introduce a new and reliable behavioral model of upper trunk of
      brachial plexus avulsion for the study of persistent neuropathic pain. 60 rats
      were divided into three groups randomly: upper trunk of brachial plexus avulsion
      (UTBPA) group (20), global brachial plexus avulsion (GBPA) group (20), and sham-
      operated group (20). The animals were tested for behavioral responsiveness before
      surgeries and 3, 7, 14, 21, 28, 56, 84days after surgeries. The injured level of
      spinal cord was resected and the sections were processed for GFAP (astrocyte) and
      Iba1 (microglia) immunohistochemistry 3 weeks after surgeries. The UTBPA group
      developed significant signs both of mechanical and cold hypersensitivity, which
      matched the immunohistochemistry result, as well as the nature of avulsion was
      close to the clinical type of injury, the UTBPA group could be used as a suitable
      and effective persistent neuropathic pain model following brachial plexus injury.

PMID- 27863699
TI  - Systematic review and meta-analysis of prostatic artery embolisation for lower
      urinary tract symptoms related to benign prostatic hyperplasia.
AB  - AIM: To evaluate the efficacy of prostatic artery embolisation (PAE) in lower
      urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) at
      short- and mid-term follow-up. MATERIALS AND METHODS: The current study included
      484 BPH patients from seven eligible studies. A meta-analysis was performed to
      determine the mean differences in parameters associated with LUTS, including the
      international prostate symptom score (IPSS), peak urinary flow (Qmax), post-void
      residual volume (PVR), quality of life score (QoL), prostate-specific antigen
      level (PSA), and prostatic volume (PV), between baseline and follow-up periods.
      RESULTS: Nearly all parameters at follow-up of 3-24 months were significantly
      improved compared to the baseline. Mean differences in IPSS at 3, 6, 12, and 24
      months were -14.06 (95% confidence interval [CI]: -16.47 to -11.64), -12.32 (95%
      CI: -15.57 to -9.08), -16.41 (95% CI: -19.81 to -13.02), and -17 (95% CI: -17.91
      to -16.09), respectively. In addition, mean differences of Qmax, PVR, PV, and QoL
      between the follow-up period and baseline were improved significantly; however,
      there were no significant differences in PSA at 24 months. CONCLUSION: The
      present data shows that PAE could improve LUTS by BPH after short- and mid-term
      follow-up; however, more cumulative studies for long-term follow-up and
      comparison with other therapeutic modalities will be needed.

PMID- 27863700
TI  - The Journal of Comparative Pathology Educational Trust 2016 Awards.

PMID- 27863698
TI  - Striatal H3K27 Acetylation Linked to Glutamatergic Gene Dysregulation in Human
      Heroin Abusers Holds Promise as Therapeutic Target.
AB  - BACKGROUND: Opiate abuse and overdose reached epidemic levels in the United
      States. However, despite significant advances in animal and in vitro models,
      little knowledge has been directly accrued regarding the neurobiology of the
      opiate-addicted human brain. METHODS: We used postmortem human brain specimens
      from a homogeneous European Caucasian population of heroin users for
      transcriptional and epigenetic profiling, as well as direct assessment of
      chromatin accessibility in the striatum, a brain region central to reward and
      emotion. A rat heroin self-administration model was used to obtain translational
      molecular and behavioral insights. RESULTS: Our transcriptome approach revealed
      marked impairments related to glutamatergic neurotransmission and chromatin
      remodeling in the human striatum. A series of biochemical experiments tracked the
      specific location of the epigenetic disturbances to hyperacetylation of lysine 27
      of histone H3, showing dynamic correlations with heroin use history and acute
      opiate toxicology. Targeted investigation of GRIA1, a glutamatergic gene
      implicated in drug-seeking behavior, verified the increased enrichment of lysine
      27 acetylated histone H3 at discrete loci, accompanied by enhanced chromatin
      accessibility at hyperacetylated regions in the gene body. Analogous epigenetic
      impairments were detected in the striatum of heroin self-administering rats.
      Using this translational model, we showed that bromodomain inhibitor JQ1, which
      blocks the functional readout of acetylated lysines, reduced heroin self
      administration and cue-induced drug-seeking behavior. CONCLUSIONS: Overall, our
      data suggest that heroin-related histone H3 hyperacetylation contributes to
      glutamatergic transcriptional changes that underlie addiction behavior and
      identify JQ1 as a promising candidate for targeted clinical interventions in
      heroin use disorder.

PMID- 27863702
TI  - Detecting asymptomatic rams infected with Mycoplasma agalactiae in ovine
      artificial insemination centers.
AB  - Mycoplasma agalactiae (Ma) is the main causative agent of ovine contagious
      agalactia, which is a serious disease of small ruminants. In endemic areas, its
      most common clinical situation consists of chronically infected herds, and
      asymptomatic infected individuals represent an epidemiological risk regarding the
      transmission of this disease. The aim of this work was to detect the presence of
      asymptomatic rams infected with Ma in different artificial insemination centers,
      and to determine the most effective way to identify these individuals so as to
      implement adequate surveillance protocols. For this purpose, 215 rams and 14
      teaser sheep were sampled taking auricular, nasal, and vaginal swabs and serum
      samples. In addition, ejaculates from 147 rams were analyzed. These samples were
      subjected to specific culture and molecular techniques to isolate and identify
      mycoplasmas, and to a serological test to detect antibodies against Ma.
      Mycoplasma agalactiae was detected in 47 (4.4%) of the 1077 samples analyzed, and
      also one individual resulted seropositive. Thus, 37 (17.2%) of the 215 studied
      rams were infected with Ma. The specimens which proportionally yielded the
      greatest number of positive results for this pathogen were semen samples (13.6%),
      followed by nasal swabs (5.8%). In contrast, the sampling of the external
      auricular canal and the serological analyses resulted insufficient to effectively
      detect infected individuals. Asymptomatic rams infected with Ma were detected in
      all the analyzed artificial insemination centers, highlighting the need to
      implement adequate surveillance protocols to prevent the presence of these
      individuals in these centers, reducing the risk of transmitting contagious
      agalactia.

PMID- 27863703
TI  - Reprint of: Object-based attentional facilitation and inhibition are
      neuropsychologically dissociated.
AB  - Salient peripheral cues produce a transient shift of attention which is
      superseded by a sustained inhibitory effect. Cueing part of an object produces an
      inhibitory cueing effect (ICE) that spreads throughout the object. In dynamic
      scenes the ICE stays with objects as they move. We examined object-centred
      attentional facilitation and inhibition in a patient with visual form agnosia.
      There was no evidence of object-centred attentional facilitation. In contrast,
      object-centred ICE was observed in 3 out of 4 tasks. These inhibitory effects
      were strongest where cues to objecthood were highly salient. These data are
      evidence of a neuropsychological dissociation between the facilitatory and
      inhibitory effects of attentional cueing. From a theoretical perspective the
      findings suggest that 'grouped arrays' are sufficient for object-based
      inhibition, but insufficient to generate object-centred attentional facilitation.

PMID- 27863701
TI  - The many wounds of war: The association of service-related and clinical
      characteristics with problems with the law in Iraq and Afghanistan veterans.
AB  - Previous research has demonstrated that veterans with posttraumatic stress
      disorder (PTSD) are at higher risk for aggression, hostility, and anger,
      potentially leading to problems with the law or disciplinary action while in the
      military. There have been calls for increased consideration of the unique aspects
      of the judicial system in legal matters with veterans involved. The bulk of the
      research so far has considered the link between PTSD, traumatic brain injury
      (TBI), and combat exposure, but little is known about the potential role of
      chronic pain and Military Sexual Trauma (MST) in a veteran's experience of anger,
      aggression, and discipline while in the military and legal concerns. The present
      study used retrospective cross-sectional health screening data in a sample of
      1250 Iraq and Afghanistan veterans to examine the associations of demographic,
      service-related, and clinical characteristics with self-reported legal problems.
      A total of 440 veterans (34.6%) endorsed having experienced some type of problems
      with the law. Independent logistic regression analyses demonstrated that those
      who screened positive for PTSD, MST, TBI, and clinical levels of pain were more
      likely to report legal problems; only the associations with positive PTSD
      (p=0.001) and MST (p=0.007) screens remained significant in multivariate
      regression analyses. The findings underscore the need for a thorough
      psychological evaluation when veterans are involved in the legal system with a
      special emphasis on factors prevalent to Iraq and Afghanistan veterans.

PMID- 27863704
TI  - Cardiovascular Effects of Glucose-lowering Therapies for Type 2 Diabetes: New
      Drugs in Perspective.
AB  - PURPOSE: The purpose of this study was to review the results of clinical trials
      assessing the cardiovascular effects of drugs for type 2 diabetes and the
      cardiovascular effects of newer available drugs. METHODS: We performed a detailed
      search of PubMed-listed publications, reports from international meetings, and
      ongoing studies from clinical trials.gov. FINDINGS: Currently available drugs
      have neutral or, in some cases, negative effects on cardiovascular outcomes.
      Modern sulfonylureas appear to be safe, although the biguanide metformin has a
      slightly better cardiovascular safety profile than the sulfonylureas and is the
      first choice for monotherapy. The cardiovascular tolerability of
      thiazolidinediones (glitazones) remains controversial, with particularly adverse
      effects in patients with cardiac failure. The cardiovascular effects of insulin
      in type 2 diabetes appear neutral. Newer incretin-based therapies have been
      closely examined in a large number of clinical trials, some of which are still
      ongoing. The dipeptidyl peptidase-4 inhibitor (gliptins) trials to date have all
      found a neutral effect. Of the glucagon-like peptide-1 (GLP-1) agonists,
      lixisenatide had a neutral effect, whereas liraglutide and semaglutide had a
      benefit on outcomes. The results of the sodium-glucose transporter-2 (SGLT-2)
      inhibitor empaglifozin attracted interest when it was the first to report a
      strong benefit on cardiovascular mortality. Liraglutide and semaglutide had a
      neutral effect on cardiac failure admissions, whereas empaglifozin had a benefit.
      In each of the trials, there was not a clear effect on myocardial infarction and
      stroke. The mechanism of the cardiovascular benefit is debated, and further
      studies with other GLP-1 agonists and SGLT-2 inhibitors are awaited.
      IMPLICATIONS: After 2 decades of disappointment in attempting to control
      cardiovascular progression in type 2 diabetes with careful glycemic control,
      there is distinct hope that newer drugs, particularly the GLP-1 agonists and the
      SGLT-2 inhibitors, will have cardiovascular benefits independent of glycemic
      control.

PMID- 27863705
TI  - Intake of selective beta blockers has no impact on survival in patients with
      epithelial ovarian cancer.
AB  - BACKGROUND AND OBJECTIVE: Some authors have claimed a significant impact of beta
      blocking agents on outcome in epithelial ovarian cancer (EOC). This study
      investigated the impact of concurrent medication with selective beta blockers
      (SBB) in patients undergoing primary treatment for EOC. METHODS: The study
      included all consecutive patients with primary EOC treated in two tertiary
      gynecological-oncologic units between 1999 and 2014. Medication was
      retrospectively analyzed by chart review. RESULTS: The study cohort comprised 801
      patients, of whom 141 (17.6%) had received SBB. Median age of patients without
      SBB medication was 56years (range: 19-90years) and 64years (range: 41-84years) in
      patients taking SBB (p<0.001). The main prognostic factor FIGO stage did not
      differ between both cohorts. 63.8% of patients taking SBB underwent complete
      tumor resection compared to 74.2% of patients without SBB (p=0.012). Patients
      without SBB experienced less severe post-operative complications according to the
      Clavien-Dindo classification (18.8% vs 29.0%; p=0.003). Between the both groups
      without and with SBB intake, PFS and OS did not differ significantly (PFS:
      27months and 24months, p=0.40; OS: 56months and 44, p=0.15). Multivariate
      analyses did not yield any association between SBB intake and prognosis but
      confirmed well-known prognostic factors. CONCLUSIONS: Intake of selective beta
      blockers did not influence the prognosis of patients with EOC.

PMID- 27863707
TI  - Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic
      ischemic encephalopathy (HIE).
AB  - In this article, we review the childhood outcomes of neonates with birth
      depression and/or hypoxic-ischemic encephalopathy. The outcomes of these children
      prior to the era of hypothermia for neuroprotection will first be summarized,
      followed by discussion of results from randomized controlled trials of
      therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy. The
      predictors of outcome in childhood following neonatal HIE using clinical and
      imaging biomarkers following hypothermia therapy will be described.

PMID- 27863706
TI  - Advanced neuroimaging and its role in predicting neurodevelopmental outcomes in
      very preterm infants.
AB  - Up to 35% of very preterm infants survive with neurodevelopmental impairments
      (NDI) such as cognitive deficits, cerebral palsy, and attention deficit disorder.
      Advanced MRI quantitative tools such as brain morphometry, diffusion MRI,
      magnetic resonance spectroscopy, and functional MRI at term-equivalent age are
      ideally suited to improve current efforts to predict later development of
      disabilities. This would facilitate application of targeted early intervention
      therapies during the first few years of life when neuroplasticity is optimal. A
      systematic search and review identified 47 published studies of advanced MRI to
      predict NDI. Diffusion MRI and morphometry studies were the most commonly studied
      modalities. Despite several limitations, studies clearly showed that brain
      structural and metabolite biomarkers are promising independent predictors of NDI.
      Large representative multicenter studies are needed to validate these studies.

PMID- 27863708
TI  - Nuclear distribution of the chromatin-remodeling protein ATRX in mouse early
      embryogenesis.
AB  - The nucleus of mammalian embryos differs by transcriptional activity at different
      stages of early development. Here, we studied nuclear distribution of the
      chromatin-remodeling protein ATRX in pre-implantation mouse embryos.
      Immunofluorescent staining revealed the changes of ATRX nuclear distribution at
      the initial stages of early mouse development. At the stage of early zygote, a
      diffuse ATRX distribution pattern was prevalent. During the course of zygotic
      genome activation (ZGA), zones of increased ATRX concentration are observed, and
      they are most expressed in the nuclei of late 2-cell embryos. In the morula
      stage, the ATRX distribution becomes diffuse again. In zygotes, the patterns of
      ATRX distribution differ between male and female pronuclei. At all the stages,
      ATRX concentrates in the DAPI-positive areas of condensed chromatin. The level of
      colocalization between ATRX and heterochromatin was found the highest at the late
      2-cell stage. When transcription was artificially suppressed, the pattern of
      intranuclear ATRX distribution was mostly determined by the mechanism of
      inhibitor action rather than the decreased level of transcriptional activity.
      Thus, the obvious changes of ATRX distribution occur and partially correlate with
      the main stages of ZGA during mouse early development, but these changes seem to
      be determined by other processes of structural and functional rearrangements of
      blastomere nuclei.

PMID- 27863709
TI  - The neuronal basis of copper induced modulation of anxiety state in rat.
AB  - Recently, studies have provided strong evidence indicating the involvement of
      trace elements in the physiopathology of psychiatric disorders, particularly
      anxiety. We aimed, through the present study, to describe the effect of acute
      exposure to Cu (10mg/kg BW) on anxiety state together with the serotoninergic and
      dopaminergic systems in rat by means of neurobehavioral tests (elevated plus
      maze, dark light box) and immunohistochemistry using anti-serotonin (5HT) and
      anti-tyrosine hydroxylase (TH). Our data report that Cu enhanced 5HT innervation
      in the dorsal raphe nucleus (DRN) together with a loss of TH expression within
      the ventral tegmental area (VTA), Substantia nigra compacta (SNc) and their
      subsequent outputs including the medial forebrain bundle (MFB) and striatum. In
      the elevated plus maze Cu significantly increased the time and the number of
      entries into the open arms, and raised the time spent in the Dark Box indicating
      a clear reduced anxiety state induced by Cu. The present data show for the first
      time a powerful neuro-modulatory potential of Cu in rat which involves primarily
      a dysfunction of 5HT and DA neurotransmissions.

PMID- 27863711
TI  - N-Acylated chitosan bis(arylcarbamate)s: A class of promising chiral separation
      materials with powerful enantioseparation capability and high eluents
      tolerability.
AB  - In order to comprehensively understand the influence of coordination of the
      substituent at 2-position with those at 3- and 6-positions on the properties of
      chitosan derivatives, a series of chitosan 3,6-bis(arylcarbamate)-2-(amide)s
      (CACAs) and the related chiral stationary phases (CSPs) were prepared and
      reported in the present study. Specifically, chitosan was N-acylated with
      carboxylic acid anhydrides, and then further derivatized with various aryl
      isocyanates to afford CACAs, from which a class of coated-type CSPs were
      prepared. When the substituent introduced on the acyl group at 2-position and
      those on the phenyl group of the carbamates at 3- and 6-positions were fittingly
      combined, these prepared CACAs based CSPs would exhibit powerful chiral
      recognition ability, further resulting in a class of promising chiral separation
      materials with excellent enantioseparation performance. Meanwhile, these newly
      developed materials with suitable molecular weight also bear a high tolerability
      towards organic solvents, even including pure tetrahydrofuran, thus broadening
      their application in enantiomeric separation.

PMID- 27863710
TI  - Predictors of remission from generalized anxiety disorder and major depressive
      disorder.
AB  - BACKGROUND: The predictors of onset of major depressive disorder (MDD) and
      generalized anxiety disorder (GAD) are well-characterized. However the factors
      that predict remission from these conditions are less clear, and the study of
      this area is further complicated by differing definitions of remission. METHODS:
      Data come from the National Comorbidity Survey - Replication, and analysis was
      limited to respondents with a lifetime history of GAD (n=621) or MDD (n=1299)
      assessed by the Composite International Diagnostic Interview. Predictors of
      remission included demographic factors, adverse childhood events, family history,
      and clinical characteristics. Multiple definitions of remission were explored to
      account for residual symptoms. RESULTS: Half (54.4%) of respondents with MDD and
      41.1% of respondents with GAD experienced full remission. Older age and higher
      socioeconomic status were positively related to remission in a dose-response
      manner for both disorders. Adverse childhood experiences and family history of
      anxious/depressive symptoms were negatively associated with remission from MDD.
      Comorbid GAD was inversely associated with remission from MDD (Odds ratio (OR):
      0.62, 95% Confidence interval (CI): 0.44-0.88), but comorbid MDD did not impact
      remission from GAD (OR: 0.93, 95% CI: 0.64-1.35). With the exception of the
      influence of comorbidity, these associations were robust across definitions of
      remission. LIMITATIONS: Cross-sectional analysis and retrospective recall of
      onset of MDD/GAD. CONCLUSIONS: Many individuals with MDD or GAD will experience
      full remission. Some predictors appear to have a general association with
      remission from both disorders, while others are uniquely associated with
      remission from MDD.

PMID- 27863712
TI  - Glycoform analysis of alpha1-acid glycoprotein by capillary electrophoresis.
AB  - A relatively fast and reproducible CE separation was developed for the glycoform
      analysis of alpha1-acid glycoprotein (AGP). Factors that were considered included
      the pH for this separation and various techniques for coating the capillary
      and/or to minimize electroosmotic flow and protein adsorption. Optimum resolution
      of the AGP glycoforms was obtained at pH 4.2 with a running buffer containing
      0.1% Brij 35 and by using static and dynamic coatings of PEO on the capillary.
      These conditions made it possible to separate nine AGP glycoform bands in about
      20min. The limit of detection (based on absorbance measurements) ranged from 0.09
      to 0.38MUM for these AGP glycoform bands, and the linear range extended up to a
      total AGP concentration of at least 240MUM. The migration times for the glycoform
      bands had typical within-day and day-to-day precisions of +/-0.16-0.23% or less,
      respectively, on a single treated capillary and the variation between capillaries
      was +/-0.56% or less. A charge ladder approach was employed to examine the mass
      or charge differences in the glycoforms that made up these bands, giving a good
      fit to a model in which the neighboring bands differed by one charge (e.g., from
      a sialic acid residue) and had an average mass difference of approximately 0.7
      0.9kDa. The approaches used to develop this separation method are not limited to
      AGP but could be extended to the analysis of other glycoproteins by CE.

PMID- 27863714
TI  - Corrigendum to "Revisiting the understanding of "transactional sex" in sub
      Saharan Africa: A review and synthesis of the literature" [Soc. Sci. Med. 168
      (2016) 186-197].

PMID- 27863713
TI  - Improving the productivity of a multidimensional chromatographic preparative
      system by collecting pure chemicals after each of three chromatographic
      dimensions.
AB  - The enhanced sample collection capability of a heart-cutting three-dimensional GC
      prep system is reported. In its original configuration, a highly pure component
      can be usually collected after the last (3D) column outlet by means of a
      dedicated preparative station. The latter is located after the last
      chromatographic column, and this poses the requirement for multiple heart cuts
      even for those components showing satisfactory degree of purity after the first
      (or second) separation dimension. The feasibility to collect pure components
      after each chromatographic dimension is here described, employing a three
      dimension MDGC system equipped with high-temperature valves, located inside the
      first and second GC ovens, with the aim to improve the productivity of the
      collection procedure. In addition to a commercial preparative collector located
      at the 3D outlet, two laboratory-made collection systems were applied in the
      first and second dimension, reached by the effluent to be collected trough a high
      temperature valve switching the heart-cut fraction between either the detector
      (FID), or the collector. Highly pure sesquiterpene components were collected,
      namely: patchouli alcohol after the first column [poly(5% diphenyl/95%
      dimethylsiloxane)], alpha-bulnesene after a second column coated with high
      molecular weight polyethylene glycol, and alpha-guaiene after an ionic-liquid
      based column (SLB-IL60), used as the third dimension. Purity levels ranging from
      85 to 95% were achieved with an average collection recovery of 90% (n=5). The
      following average amounts were collected per run: 160MUg for alpha-guaiene,
      295MUg for alpha-bulnesene, and 496MUg for patchouli alcohol.

PMID- 27863715
TI  - Kawasaki disease and immunisation: Standardised case definition & guidelines for
      data collection, analysis.

PMID- 27863716
TI  - Antibodies against the C-terminus of alpha-synuclein modulate its fibrillation.
AB  - The 140-residue natively disordered protein alpha-synuclein (aSN) is a central
      component in the development of a family of neurodegenerative diseases termed
      synucleinopathies. This is attributed to its ability to form cytotoxic aggregates
      such as oligomers and amyloid fibrils. Consequently there have been intense
      efforts to avoid aggregation or reroute the aggregation pathway using
      pharmaceutical agents such as small molecules, chaperones and antibodies. aSN's
      lack of persistent structure in the monomeric state, as well as the multitude of
      different oligomeric and even different fibrillar states, makes it difficult to
      raise antibodies that would be efficacious in neutralizing all conformations of
      aSN. However, the C-terminal 20-40 residues of aSN are a promising epitope for
      antibody development. It is primarily disordered in both monomeric and aggregated
      forms, and an anti-C-terminal antibody will therefore be able to bind all forms.
      Furthermore, it might not interfere with the folding of aSN into membranes, which
      could be important for its physiological role. Here we report a screen of a
      series of monoclonal antibodies, which all target the C-terminal of aSN.
      According to dot blot analyses, different antibodies bound different forms of aSN
      with different preferences and showed reduced binding to monomeric compared to
      aggregated (oligomeric and fibrillary) aSN. Consequently they have different
      effects on aSN's ability to fibrillate and permeabilize membranes. Generally, the
      antibodies with strongest binding to aggregated aSN in dot blot, also inhibited
      fibrillation and membrane permeabilization the most, and promoted formation of
      amorphous aggregates surrounded by small and thin fibers. This suggests that the
      development of antibodies that targets the C-terminus, exposed in the aggregated
      forms of aSN, may be beneficial for improved immunotherapy against PD.

PMID- 27863717
TI  - Finding routes towards understanding and the successful correction of presbyopia.

PMID- 27863718
TI  - The impact of immediate breast reconstruction after mastectomy on time to first
      adjuvant treatment in women with breast cancer in a community setting.
AB  - BACKGROUND: The impact of immediate breast reconstruction on the time to first
      adjuvant therapy is controversial. METHODS: Retrospective study design comparing
      time to first treatment in women undergoing mastectomy with and without immediate
      reconstruction in a community cancer center. RESULTS: Seventy-six cases fit
      inclusion criteria of which 44 (58%) underwent mastectomy with immediate
      reconstruction. Women undergoing immediate reconstruction were younger, had more
      bilateral mastectomies and had fewer prior breast procedures. The median time to
      first adjuvant therapy was longer in the immediate reconstruction group [80.5days
      (36-343) versus 53.5 days (18-96), p = 0.003]. Fifteen of 44 patients had the
      start of adjuvant treatment over 90 days after resection, 14 of whom (93%) had
      immediate reconstruction versus 1 (7%) who did not (p = 0.01). CONCLUSION: In
      this study immediate breast reconstruction was associated with a longer time to
      first adjuvant treatment, with adjuvant therapies being more likely delayed over
      90 days.

PMID- 27863719
TI  - Utility of feeding jejunostomy tubes in pancreaticoduodenectomy.
AB  - BACKGROUND: Routine placement of jejunostomy tubes (JT) during
      pancreaticoduodenectomy (PD) is controversial. METHODS: A retrospective chart
      review of patients undergoing PD from 1/1/08 through 12/31/14 was performed. The
      patients were divided into groups by placement of JT. Outcome measures were 90
      day morbidity, 90-day mortality, length of stay, rate of delayed gastric emptying
      (DGE), and JT-specific complications. RESULTS: 256 patients were included. There
      were no significant differences in 90-day morbidity (39.9% vs. 37.9%, p = 0.747),
      90-day mortality (3.9% vs. 1.0%, p = 0.247) or TPN use (24.8 vs. 25.2%, p =
      0.941) between those with and without JT, respectively. Patients with a JT had a
      higher rate of DGE (p < 0.001), longer hospital stay (14.3 vs. 11.6, p < 0.001),
      and longer time to solid intake (9.4 vs. 7.3, p < 0.001). Eleven patients (7.2%)
      with JT had tube-related morbidity. CONCLUSIONS: Routine placement of JT at the
      time of PD should be abandoned with efforts focused on preoperative nutrition
      optimization and early oral diet trials.

PMID- 27863720
TI  - Can residents detect errors in technique while observing central line insertions?
AB  - BACKGROUND: Procedural teaching and the ability to detect and correct errors are
      important components of surgical education. This study evaluates whether review
      of an instructional video will improve residents' ability to detect errors. We
      hypothesized that clinical experience and confidence do not correlate with
      ability to detect errors. METHODS: Participants were randomized to 2 groups: the
      study group viewed an instructional video demonstrating correct technique,
      whereas the control group did not view the instructional video. Forty general
      surgery residents described errors in technique during an ultrasound-guided right
      internal jugular vein catheterization pre and post randomization. RESULTS:
      Participants who viewed the video improved their error identification rate by
      72.6% (P < .001). No correlation between postgraduate year or confidence in error
      detection and the actual ability to detect errors was noted (r = .17 and r = .14
      respectively). CONCLUSIONS: Experience and seniority may not be sufficient to
      detect procedural errors during central line insertion. Instructional videos
      improve error recognition.

PMID- 27863721
TI  - Ambulatory bilateral neck exploration for primary hyperparathyroidism: Is it
      safe?

PMID- 27863723
TI  - Actually, guns Do kill people.

PMID- 27863722
TI  - Is nasotracheal intubation safe in facial trauma patients?
AB  - BACKGROUND: In the prehospital setting, oral intubation is preferred in facial
      trauma patients due to the potential for further injury during nasotracheal
      intubation. This study compared the complications of nasal vs. oral vs. nasal +
      oral intubations performed by first responder crews in facial trauma patients.
      Our objective was to assess patient outcomes and complications to determine the
      risk of nasal intubation in facial trauma patients in the prehospital setting.
      METHODS: Patients with facial trauma between 2008 and 13 were abstracted from the
      Miami Valley Hospital trauma registry: 50 were nasal only (n), 27 nasal + oral
      (no), and 135 oral only (o) intubation. Analysis of variance with the post-hoc
      Least Significance Difference Test and the chi square test were used in the
      analysis. RESULTS: The oral group was older [41.1 +/- 17.6 (o) vs. 36.2 +/- 14.1
      (n) vs. 33.0 +/- 15.7 (no), p = 0.032] and had a higher facial abbreviated injury
      severity (AIS) mean score (1.8 +/- 0.6 vs. 1.3 +/- 0.5 vs. 1.5 +/- 0.5, p <
      0.001). The three groups did not differ in mortality (n = 20% vs. o = 18% vs. no
      = 30%, p = 0.37). The n + o group was intubated longer (p < 0.001) and had longer
      ICU and hospital lengths of stay (p = 0.015 and p = 0.023). The three groups did
      not differ on the composite of any pulmonary complication - i.e., any one of
      sinusitis, pneumonia, atelectasis, and respiratory failure - 44% (no) vs. 24% (o)
      vs. 30% (n), p = 0.10). However, nasal + oral patients were more likely to have
      one or more of the eight complication studied [63% (no) vs. 28% (o) vs. 34% (n),
      p = 0.002], and have a longer ICU and HLOS. CONCLUSIONS: Prehospital nasal
      intubation is a viable short-term alternative to oral intubation in patients with
      facial trauma and warrants further research.

PMID- 27863724
TI  - [Which approach of therapeutic education (TE) for adolescents and young adults
      with cancer? Experience from the TE working group of "Go-AJA"].
AB  - INTRODUCTION: Therapeutic education (TE) is a practice developed over 40 years at
      an international level to give people with chronic illness the skills necessary
      to help them better manage their disease. The lengthening survival time of cancer
      patients as well as changes in the patient-caregiver relationship have
      contributed to the development of TE in oncologic diseases. Every year in France,
      about 1900 adolescents and young adults (15-25 years old) are diagnosed with
      cancer which is the second leading cause of death in this age group. The observed
      survival rates for these patients are lower when compared with children's. Some
      of the hypotheses put forward to explain this difference include a lack of
      constancy in care and a non-following treatment, as failure to adhere to
      therapies is common in this age group. "Go-AJA", an interdisciplinary national
      organization established in 2012, aims to improve the quality of care and
      treatment results for AYA living with cancer. Therapeutic education for AYA in
      oncology is an active working group of "Go-AJA" and intends to draw
      recommendations and to improve adapted communication on different education
      topics. Elaboration and preparation of TE programs by skilled multidisciplinary
      teams engaged in interactive educational actions is the first and most crucial
      step. MATERIALS AND METHODS: The TE "Go-AJA" working group has federated
      pediatric and adult oncologists, nurses, psychologists, TE professionals, and
      resource patients, thanks to the commitment of professionals from the 8 national
      teams supported by the National Cancer Institute. Physical meetings and
      conference calls were organized from 2012 to 2015 to construct TE tools and
      programs for AYA with cancer. RESULTS: A competence referential was built and
      adapted to AYA population with cancer, after focused groups organized in 2 main
      oncology centers with on-therapy sarcoma patients and members of the
      multidisciplinary TE working group. Tools were validated and adapted to
      adolescents or young adults with cancer, to help in the 4 stages of TE: the
      "educational diagnosis" allowing the caregiver to better understand the patient
      in his life journey with the disease; the "therapeutic alliance" allowing to
      agree with the patient on his/her priorities; the "implementation" which is an
      action step: information, awareness, learning and psychosocial support. The final
      step called "assessment" allows the caregiver to take stock on the changes and
      difficulties with the patient. TE for AYA with cancer included individual and/or
      group sessions to improve self-care skills: knowledge about the disease (group
      sessions "what is cancer?" with use of microscopes to visualize sarcoma cells,
      and guided tours in a tumor research laboratory), and details about the treatment
      and its consequences (workshops about "management of febrile neutropenia").
      Moreover, TE aimed to enrich the field of coping skills, in particular to improve
      the coordination and experience of cares between the different complex and varied
      network of care (group and/or individual sessions focused on physical
      rehabilitation, and adapted school/professional orientation). CONCLUSION:
      Regardless of the care system, care workers dedicated to AYA with cancer should
      use TE-specific actions to reinforce treatment participation and therapeutic
      relationships. This active multidisciplinary TE working group dedicated to AYA
      with cancer elaborated TE programs by skilled multidisciplinary teams engaged in
      interactive educational actions. After this work of a national TE organization,
      more studies using methodological tools are still required to evaluate the impact
      of such implemented programs on the treatment results and the quality of life.

PMID- 27863725
TI  - [What specific socialisation, social, educational and professional for teenagers
      and young adults with cancer?]
AB  - Socialisation, education, first jobs and autonomy are key steps to teenagers and
      young adults (TYA) integration into the society. The occurrence of a cancer in
      this population increases the difficulties. Although, suffering of cancer do
      affect TYA life journey at social, scholar and professional levels, from
      diagnosis to the after-cancer live and sometime forever, few studies exist in
      France. A national study on TYA with cancer (TYAC) social, scholar and
      professional pathways is on-going (ESPOIR-AJA). A national survey of the existing
      TYAC insertion support in 2013 by the "Insertion group" of groupe onco
      hematologie adolescents et jeunes adultes (GO-AJA) revealed structured and
      ancient support at scholar level based on national governmental or associative
      structures, but insufficient and non-specific scholar help in secondary school
      and professional help. Specific initiatives have emerged since 2012 with the
      "Plan cancer 2". All these helps remain unequal across the country. A referential
      on TYAC social, scholar and professional insertion has been prepared by GO-AJA in
      collaboration with the association francophone des soins oncologiques de support
      (AFSOS). The impact of the action 9 of the nation "plan cancer 3" is awaited.

PMID- 27863726
TI  - [MET receptor inhibition: Hope against resistance to targeted therapies?]
AB  - Overcoming the drug resistance remains a crucial issue in cancer treatment. For
      refractory patients, the use of MET receptor tyrosine kinase inhibitors seems to
      be hopeful. Indeed, important mechanisms underlying drug resistance argue for
      association of MET inhibitors with targeted therapies, both on first-line to
      prevent a primary resistance and on the second line to overcoming acquired
      resistance. Indeed, met gene amplification is the second most common alteration
      involved in acquired resistance to anti-epidermal growth factor receptor (EGFR)
      therapies in non-small cells lung cancer (NSCLC). Hypoxia, for its part, can
      activate MET transcription and amplifies HGF signaling resulting in MET
      activation, which could be involved in vascular endothelial growth factor (VEGF)
      inhibitors escape. In HER2 positive breast cancers, MET amplification may also
      induce tumor cells a hatch escape, resulting in secondary resistance. Finally,
      some patients with BRAF mutated melanoma exhibit primary resistance to BRAF
      inhibition by stromal HGF (ligand of MET) secretion resulting in MET receptor
      activation. Experimental data highlight the role of MET in primary and secondary
      resistance and encourage combined treatments including MET inhibitors. In this
      context, several promising clinical trials are in progress in numerous cancers
      (NSCLC, melanoma, breast cancer, glioblastoma...) using combination of anti-MET
      and other specific therapies targeting EGFR, BRAF, VEGF or HER2. This review
      summarizes the potential benefits that MET inhibition should provide to patients
      with cancer refractory to targeted therapies.

PMID- 27863729
TI  - Outcomes of Anterolateral Thoracotomy With or Without Partial Sternotomy for
      Kommerell Diverticulum.
AB  - BACKGROUND: Kommerell diverticulum is a rare aortic arch anomaly. The indications
      for operative intervention and surgical strategy are still controversial. The
      standard surgical procedure at our institution is total aortic arch plus
      descending aortic replacement using anterolateral thoracotomy with partial
      sternotomy. The aberrant subclavian artery is reconstructed anatomically or
      extraanatomically. METHODS: From 2002 to 2014, 6 patients (1 woman), aged 55 to
      78 years, underwent graft replacement through an anterolateral thoracotomy or
      anterolateral thoracotomy with a partial sternotomy approach for Kommerell
      diverticulum. All patients underwent graft replacement of the descending aorta or
      total aortic arch plus descending aorta in addition to aberrant subclavian artery
      reconstruction. RESULTS: No hospital deaths or major complications occurred.
      Recurrent nerve injury developed at discharge in 1 patient. All patients were
      well during the follow-up period (range, 11 to 116 months). CONCLUSIONS:
      Kommerell diverticulum and its associated symptoms were surgically treated with
      acceptable outcomes.

PMID- 27863728
TI  - Fontan Patient Survival After Pediatric Heart Transplantation Has Improved in the
      Current Era.
AB  - BACKGROUND: Historically, patients with a prior Fontan procedure for complex
      congenital heart disease (CHD) have been considered at higher risk for death
      after heart transplant (HT) compared with other HT transplant candidates. With
      the overall trend of improved survival of pediatric HT recipients, it is unclear
      of Fontan patient post-HT survival has also improved in the current era. METHODS:
      Data from the Pediatric Heart Transplant Study database for Fontan patients who
      underwent HT was compared between the early era (1993 to 2006, n = 150) and late
      era (2007 to 2014, n = 252). Post-HT survival and pre-HT characteristics were
      compared among eras and also with non-Fontan CHD patients. RESULTS: At time of
      HT, Fontan patients in the late era were more likely to require inotropic
      support, have protein-losing enteropathy, have failure to thrive, and be further
      from time of Fontan, although less likely to be on ventilator support. Only
      ventilator support and earlier year of HT were significant risk factors for death
      in the multivariate analysis. Post-HT Fontan patient survival significantly
      improved from the early to late era (p = 0.02), particularly in the early phase,
      with 1-year survival of 77% in the early era and 89% in the late era. Late era
      non-Fontan CHD patient 1-year post-HT survival was similar to Fontan patients at
      92%. CONCLUSIONS: Survival of Fontan patients after HT has significantly improved
      in the current era. Currently, expected post-HT survival for Fontan patients is
      on par with other CHD patients. Fontan patients should not be excluded from
      consideration for HT solely on a history of Fontan.

PMID- 27863730
TI  - Psoas Muscle Area and Length of Stay in Older Adults Undergoing Cardiac
      Operations.
AB  - BACKGROUND: Frailty assessment can help predict which older adults will
      experience adverse events after cardiac surgical procedures. Low muscle mass is a
      core component of frailty that is suboptimally captured by self-reported weight
      loss; refined measures using computed tomographic (CT) images have emerged and
      are predictive of outcomes in noncardiac surgical procedures. The objective of
      this study was to evaluate the association between CT muscle area and length of
      stay (LOS) after cardiac surgical procedures. METHODS: Frail patients who had a
      perioperative abdominal or thoracic CT scan were identified. The CT scans were
      analyzed to measure cross-sectional lean muscle area at the L4 vertebra (psoas
      muscle area [PMA], lumbar muscle area [LMA]) and the T4 vertebra (thoracic muscle
      area [TMA]). The associations of PMA, LMA, and TMA with frailty markers and
      postoperative LOS were investigated. RESULTS: Eighty-two patients were included;
      the mean age was 69.2 +/- 9.97 years. Low muscle area was correlated with lower
      handgrip strength and short physical performance battery (SPPB) scores indicative
      of physical frailty. Postoperative LOS was correlated with PMA (R = -0.47, p =
      0.004), LMA (R = -0.41, p = 0.01), and TMA (R = -0.29, p = 0.03). After
      adjustment for the predicted risk of prolonged LOS, age, sex, and body surface
      area, PMA remained significantly associated with LOS (beta = -2.35, 95% CI -4.48
      to -0.22). The combination of low PMA and handgrip strength, indicative of
      sarcopenia, yielded the greatest incremental value in predicting LOS.
      CONCLUSIONS: Low PMA is a marker of physical frailty associated with increased
      LOS in older adults undergoing cardiac surgical procedures. Further research is
      necessary to validate PMA as a prognostic marker and therapeutic target in this
      vulnerable population.

PMID- 27863731
TI  - Pulmonary Resection for Synchronous M1b-cStage IV Non-Small Cell Lung Cancer
      Patients.
AB  - BACKGROUND: We wanted to assess the efficacy of curative intent pulmonary
      resection for non-small cell lung cancer (NSCLC) patients with synchronous M1b
      distant metastases in a single organ or lesion. METHODS: Between 1995 and 2015,
      23 consecutive synchronous M1b-cStage IV NSCLC patients who underwent any
      treatment for metastases and curative intent pulmonary resection were
      retrospectively analyzed. RESULTS: Sixteen patients were men and 7 were women,
      with a median age of 56 years (range: 41 to 76 years). There were 17
      adenocarcinoma, 4 large-cell carcinoma, 1 large-cell neuroendocrine cancer, and 1
      carcinosarcoma. Thirteen patients had no lymph node metastasis. Fourteen patients
      received preoperative chemotherapy, and 10 received postoperative chemotherapy.
      The metastatic sites were the brain in 13 patients; bone in 3 patients; adrenal
      glands and extrathoracic lymph nodes in 2 patients each; and the liver, small
      intestine, and subcutaneous tissue in 1 patient each. Nineteen patients underwent
      lobectomy, and the other 4 patients underwent pneumonectomy. Seventeen patients
      experienced recurrence as follows: local recurrence in 3 patients, distant
      recurrence in 13 patients, and both in 1 patient. The 5-year progression-free
      survival rates in the 23 patients was14.5% (95% confidence interval: 0% to
      30.6%), and the 5-year overall survival rate was 41.7% (95% confidence interval:
      19.6% to 63.8%). CONCLUSIONS: Some M1b-cStage IV NSCLC patients achieved longer
      survival than others with the same stage disease by using local treatment for
      distant metastases and curative intent pulmonary resection. Oligometastatic
      patients might have been inadvertently included in the present cohort. However,
      at present, the optimum method for patient selection remains unclear.

PMID- 27863732
TI  - Efficacy of Aortic Valve Resuspension in Establishing Valve Competence in Acute
      Type A Dissections.
AB  - BACKGROUND: This study investigates the efficacy of aortic valve (AV)
      resuspension with preservation of the native aortic root in maintaining AV
      competence during type A dissection repair. METHODS: A total of 154 acute type A
      dissection repairs were performed from January 2000 to July 2015. AV resuspension
      was performed in 120 patients to address AV insufficiency (AI). Survival data
      were derived from 120 patients who had AV resuspensions and all 154 acute type A
      dissection repairs. RESULTS: Of the 70 patients who presented initially with
      moderate-to-severe AI, 43 underwent AV resuspension. Echocardiographic data for
      analysis were available in 40 of these 43 patients. In the group with moderate-to
      severe AI at presentation, AV resuspension was able to achieve mild or less AI in
      38 of 40 patients (95%) and trivial or no AI in 29 of 40 patients (73%) after
      weaning from cardiopulmonary bypass. The presence of moderate-to-severe
      preoperative AI did not predict the ability to achieve trivial or no AI with
      resuspension immediately after coming off cardiopulmonary bypass (p = 0.3) or on
      subsequent follow-up (p = 0.8). Mean echocardiographic follow-up for AV
      resuspension was 1.21 +/- 2.57 years. Three patients who underwent AV
      resuspension required AV reoperation at follow-up. There was no survival
      difference between patients who did or did not have AV resuspension (p = 0.3).
      CONCLUSIONS: AV resuspension is able to improve valve competency with good
      outcomes even in patients with moderate or severe AI at presentation. Overall
      long-term survival is unchanged compared with other operative strategies for the
      AV.

PMID- 27863733
TI  - Impact of Left Ventricular Systolic Function on Outcome of Correction of Chronic
      Severe Aortic Valve Regurgitation: Implications for Timing of Surgical
      Intervention.
AB  - BACKGROUND: The timing of valve repair or replacement in patients with severe
      aortic valve regurgitation (AR) is controversial. We investigated the effect of
      left ventricular (LV) function on survival and recovery of LV performance and
      dimensions after correction of chronic severe AR. METHODS: We reviewed 530
      consecutive patients who underwent aortic valve repair or replacement for severe
      AR between January 1, 2004, and June 30, 2014. RESULTS: The 30-day mortality was
      0.75%. In multivariate analysis, older age (hazard ratio [HR] = 1.02, p = 0.03),
      preoperative LV ejection fraction (EF) <60% (HR = 1.78, p = 0.04), previous
      myocardial infarction (HR = 2.53, p = 0.01), and previous cardiac operation (HR =
      1.82, p = 0.03) were associated with all-cause mortality. Ejection fraction was
      reduced before hospital discharge but then improved and was greater than
      preoperative levels at all subsequent intervals. The LV dimensions decreased
      early postoperatively and continued to decrease thereafter. In multivariate
      analysis, factors associated with LV dysfunction (EF <60%) 1 year after aortic
      valve replacement were preoperative LV end-systolic dimension >=40 mm (odds ratio
      [OR] = 5.39, p < 0.01) and previous myocardial infarction (OR = 3.62, p = 0.04).
      CONCLUSIONS: Preoperative LV dysfunction (EF <60%) had an adverse effect on
      overall survival after correction of chronic severe AR. Because survival is
      improved in patients with greater preoperative LVEF and because reverse LV
      remodeling is more complete with smaller LV dimensions, surgical intervention
      should be considered promptly in patients with chronic severe AR and
      deterioration of these indicators during echocardiographic surveillance.

PMID- 27863734
TI  - Provider-parent Communication When Discussing Vaccines: A Systematic Review.
AB  - PROBLEM: Expert literature on communication practices with vaccine hesitant
      parents posits that a non-confrontational/participatory discussion with the
      parent would be the best approach to improve compliance. A prior literature
      review found limited evidence to recommend any particular face to face
      intervention other than to incorporate communication about vaccination
      effectiveness during an encounter. Hence, a systematic review was performed in an
      attempt to determine the most efficacious communication practices to use with
      parents with vaccination concerns. ELIGIBILITY CRITERIA: Quantitative and
      qualitative studies written in English that assessed the communication
      framework/style of the provider-parent interaction and studies where provider
      communication was listed as an intervention were reviewed. SAMPLE: Nine articles
      were included in the sample. RESULTS: The majority of the studies were
      descriptive and qualitative in nature with only one randomized controlled trial.
      Five of the 9 studies utilized a descriptive cross-sectional design. Two main
      themes included message types recommended or given by the provider and message
      types that were requested by the parent. CONCLUSIONS: Overall, findings showed
      that there is currently not enough information to definitively state the type of
      provider-parent communication style that should be employed to affect the
      parents' vaccination viewpoint. However, recurring themes of trust in the
      provider and a personalized provider-parent interaction were evident, which
      promotes a participatory type of interaction. IMPLICATIONS: The literature
      indirectly supports providers engaging with vaccine hesitant parents in a more
      individualized, participatory format, though higher quality and more rigorous
      studies that focus specifically on provider-parent communication practices are
      needed.

PMID- 27863735
TI  - Validity and reliability of the Functional Dexterity Test in children.
AB  - STUDY DESIGN: Clinical measurement study. INTRODUCTION: The Functional Dexterity
      Test (FDT) has not been validated in children. PURPOSE OF THE STUDY: To determine
      reliability and validity of the FDT in a pediatric population. METHODS:
      Intraclass Correlation Coefficients (ICCs) were used to calculate interrater and
      test-retest reliability in typically developing children. Pearson correlation
      coefficients were used to compare FDT speed with the Jebsen-Taylor Hand Function
      Test (JHFT) and with 2 activities of daily living tasks to establish validity in
      children with congenital hand differences. RESULTS: The FDT demonstrated
      excellent interrater (ICC, 0.99) and test-retest (ICC, 0.90) reliability. Pearson
      correlation coefficients exceeded 0.67 for JHFT subsets of fine dexterity and
      were all less than 0.66 for JHFT subsets of gross grasp. Correlations with the
      activities of daily living tasks were good to excellent. FDT speeds in TD
      children exceeded those of children with congenital hand differences (P < .001),
      demonstrating discriminant validity. DISCUSSION: Children with congenital hand
      differences are often treated early in life, making it important to reliably
      assess hand function of these young children to distinguish developmental change
      from changes due to interventions. The FDT can reliably measure functional
      progress over time, help clinicians monitor the efficacy of treatment, and
      provide families realistic feedback on their child's progress. CONCLUSION: The
      FDT is a valid and reliable instrument for the measurement of fine motor
      dexterity in children.

PMID- 27863736
TI  - Moberg Picking-Up Test in patients with hand osteoarthritis.
AB  - STUDY DESIGN: Clinical measurement. INTRODUCTION: The Moberg Pick-up Test (MPUT)
      was previously used to evaluate functional performance in patients with hand
      inflammatory disease. This is the first study using the MPUT in hand
      osteoarthritis (OA). PURPOSE OF THE STUDY: Compare the functional performance
      (MPUT) in hand OA patients and healthy controls. METHODS: Fifty hand OA patients
      and 50 controls were assessed using the MPUT, AUSCAN and Cochin questionnaires,
      grip and pinch strength, pain using a visual analog scale and a Likert scale
      regarding difficulty to perform MPUT. RESULTS: In the MPUT evaluation, the OA
      group presented a statistically significant difference from the control group.
      The OA group spent more time executing test. The grip and pinch strength
      measurements showed higher values for the control group. The OA group reported a
      greater difficulty than the control group in performing the test. CONCLUSION: The
      MPUT is a short and easy to apply test, which can be safely used to assess the
      functional performance of the hand OA. LEVEL OF EVIDENCE: II.

PMID- 27863738
TI  - Presence of an adsorbent cake layer improves the performance of gravity-driven
      membrane (GDM) filtration system.
AB  - Gravity-driven membrane (GDM) filtration is a promising decentralized drinking
      water treatment process. To improve the performance of GDM system, a thin layer
      of adsorbent was pre-deposited on the membrane surface prior to filtration
      (adsorbent-laden GDM system). The tested adsorbents include powdered activated
      carbon (PAC) and anion exchange resin (AER), and an unmodified GDM system and a
      SiO2-laden GDM system were used as controls. In the adsorbent-laden GDM systems,
      the adsorption of the PAC and AER increased the removal efficiency of natural
      organic matter by 7.2-43.5% and microcystin-LR, atrazine, and bisphenol A by 7.9
      81.2%. The presence of adsorbent particles increased the amount of microorganisms
      in the cake layer and therefore increased the removal efficiency of assimilable
      organic matter (AOC) by 20.1-34.4%. In the adsorbent-laden GDM systems, the
      physically irrecoverable fouling decreased because of the reduction in membrane
      foulants by the adsorbent layer. However, the presence of adsorbent particles in
      the cake layer counteracted this effect and increased the physically recoverable
      fouling. Consequently, the pre-deposited adsorbent layers had only a limited
      effect on the stabilized flux (2.26-2.65 L/m2 h). A bilayer structure was found
      in the cake layer of the adsorbent-laden GDM systems via scanning electron
      microscopy (SEM), and the cake layer was looser in the presence of adsorbent
      particles. These results demonstrate that pre-depositing a thin layer of
      adsorbents on the membrane surface of the GDM system can significantly improve
      the quality of the permeate without decreasing the stabilized flux.

PMID- 27863737
TI  - Intensified nitrate and phosphorus removal in an electrolysis -integrated
      horizontal subsurface-flow constructed wetland.
AB  - A novel electrolysis-integrated horizontal subsurface-flow constructed wetland
      system (E-HFCWs) was developed for intensified removal of nitrogen and phosphorus
      contaminated water. The dynamics of nitrogen and phosphorus removal and that of
      main water qualities of inflow and outflow were also evaluated. The hydraulic
      retention time (HRT) greatly enhanced nitrate removal when the electrolysis
      current intensity was stabilized at 0.07 mA/cm2. When the HRT ranged from 2 h to
      12 h, the removal rate of nitrate increased from 20% to 84%. Phosphorus (P)
      removal was also greatly enhanced-exceeding 90% when the HRT was longer than 4 h
      in the electrolysis-integrated HFCWs. This improved P removal is due to the in
      situ formation of ferric ions by anodizing of sacrificial iron anodes, causing
      chemical precipitation, physical adsorption and flocculation of phosphorus. Thus,
      electrolysis plays an important role in nitrate and phosphorus removal. The
      diversity and communities of bacteria in the biofilm of substrate was established
      by the analysis of 16S rDNA gene sequences, and the biofilm was abundant with
      Comamonadaceae and Xanthomonadaceae bacteria in E-HFCWs. Test results illustrated
      that the electrolysis integrated with horizontal subsurface-flow constructed
      wetland is a feasible and effective technology for intensified nitrogen and
      phosphorus removal.

PMID- 27863739
TI  - The influence of testing angle on the biomechanical properties of the rat
      supraspinatus tendon.
AB  - Rotator cuff tears are a common shoulder pathology. The rat supraspinatus tendon
      model is commonly employed for preclinical assessment of rotator cuff pathology
      or regeneration. However, there is a lack of a standardized biomechanical testing
      protocol; previous studies have tested the tendon at abduction angles ranging
      from -15 degrees  to 90 degrees . This study aimed to assess the effect of
      abduction/testing angle on the biomechanical properties of the rat supraspinatus
      tendon. Fourty-eight shoulders (n=12/group) from healthy Sprague-Dawley rats were
      randomized to 4 testing angle groups: 0 degrees  (corresponding to 90 degrees 
      abduction), 30 degrees , 60 degrees , and 90 degrees  (0 degrees  abduction).
      Biomechanical testing of the supraspinatus was performed, consisting of stress
      relaxation and load-to-failure. Mechanical properties were calculated, and
      nonlinear tensile modeling was performed via the Quasilinear Viscoelastic (QLV)
      and Structurally Based Elastic (SBE) models. Results indicate that testing angle
      significantly affects supraspinatus tendon biomechanics. Stiffness and modulus
      significantly decreased with increasing testing angle (stiffness: 20.93+/-5.8N/mm
      at 0 degrees  vs. 6.12+/-1.0N/mm at 90 degrees , P<.001; modulus: 59.51+/-34.0MPa
      at 0 degrees  vs. 22.37+/-7.4MPa at 90 degrees , P=.002). Testing angle
      correlated significantly to ultimate strain, yield strain, and all coefficients
      of the SBE and QLV models, implying differences in collagen fiber crimp patterns
      and viscoelastic behavior as a function of testing angle. These results suggest
      that differences in testing methodology, in particular testing angle,
      significantly affect the measured mechanical properties of the supraspinatus
      tendon. Future studies may consider utilizing testing angles of 0 degrees -30
      degrees , at which tendon stiffness is maximized, and full standardization of rat
      rotator cuff testing protocols is necessary.

PMID- 27863740
TI  - Understanding the fluid mechanics behind transverse wall shear stress.
AB  - The patchy distribution of atherosclerosis within arteries is widely attributed
      to local variation in haemodynamic wall shear stress (WSS). A recently-introduced
      metric, the transverse wall shear stress (transWSS), which is the average over
      the cardiac cycle of WSS components perpendicular to the temporal mean WSS
      vector, correlates particularly well with the pattern of lesions around aortic
      branch ostia. Here we use numerical methods to investigate the nature of the
      arterial flows captured by transWSS and the sensitivity of transWSS to inflow
      waveform and aortic geometry. TransWSS developed chiefly in the acceleration,
      peak systolic and deceleration phases of the cardiac cycle; the reverse flow
      phase was too short, and WSS in diastole was too low, for these periods to have a
      significant influence. Most of the spatial variation in transWSS arose from
      variation in the angle by which instantaneous WSS vectors deviated from the mean
      WSS vector rather than from variation in the magnitude of the vectors. The
      pattern of transWSS was insensitive to inflow waveform; only unphysiologically
      high Womersley numbers produced substantial changes. However, transWSS was
      sensitive to changes in geometry. The curvature of the arch and proximal
      descending aorta were responsible for the principal features, the non-planar
      nature of the aorta produced asymmetries in the location and position of streaks
      of high transWSS, and taper determined the persistence of the streaks down the
      aorta. These results reflect the importance of the fluctuating strength of Dean
      vortices in generating transWSS.

PMID- 27863741
TI  - Shear targeted drug delivery to stenotic blood vessels.
AB  - In this review we focus on shear targeted drug delivery as a novel strategy to
      selectively deliver drugs to sites of vascular obstruction. We review the physics
      of stenotic (abnormally narrowed) blood vessels, while focusing mainly on the
      hemodynamics and transport phenomena at these sites. We then discuss how the
      local abnormal levels of shear stress, which can mechanically activate platelets,
      can be leveraged for localized drug delivery. We describe the development of
      Shear Activated Nano-particle Aggregates (SA-NPAs) that are designed to release
      and localize their nanoparticle drug carriers at sites of vascular stenosis. We
      present results in a variety of in vivo models, demonstrating the superiority of
      SA-NPAs carrying a thrombolytic drug compared to conventional treatment with the
      free drug. We also describe, shear-stress sensitive lenticular liposomes, which
      also show selective release under stenotic flow conditions. We then discuss
      limitations of both technologies, challenges in this new field and potential
      future applications. Altogether, we believe that mechano-sensitive therapeutics
      may offer a potential new approach for treatment of cardiovascular diseases.

PMID- 27863743
TI  - In vitro and in silico approaches to quantify the effects of the Mitraclip(r)
      system on mitral valve function.
AB  - Mitraclip(r) implantation is widely used as a valid alternative to conventional
      open-chest surgery in high-risk patients with severe mitral valve (MV)
      regurgitation. Although effective in reducing mitral regurgitation (MR) in the
      majority of cases, the clip implantation produces a double-orifice area that can
      result in altered MV biomechanics, particularly in term of hemodynamics and
      mechanical stress distribution on the leaflets. In this scenario, we combined the
      consistency of in vitro experimental platforms with the versatility of numerical
      simulations to investigate clip impact on MV functioning. The fluid dynamic
      determinants of the procedure were experimentally investigated under different
      working conditions (from 40bpm to 100bpm of simulated heart rate) on six swine
      hearts; subsequently, fluid dynamic data served as realistic boundary conditions
      in a computational framework able to quantitatively assess the post-procedural MV
      biomechanics. The finite element model of a human mitral valve featuring an
      isolated posterior leaflet prolapse was reconstructed from cardiac magnetic
      resonance. A complete as well as a marginal, sub-optimal grasping of the leaflets
      were finally simulated. The clipping procedure resulted in a properly coapting
      valve from the geometrical perspective in all the simulated configurations.
      Symmetrical complete grasping resulted in symmetrical distribution of the
      mechanical stress, while uncomplete asymmetrical grasping resulted in higher
      stress distribution, particularly on the prolapsing leaflet. This work pinpointed
      that the mechanical stress distribution following the clipping procedure is
      dependent on the cardiac hemodynamics and has a correlation with the proper
      execution of the grasping procedure, requiring accurate evaluation prior to clip
      delivery.

PMID- 27863742
TI  - Nanoparticle transport and delivery in a heterogeneous pulmonary vasculature.
AB  - Quantitative understanding of nanoparticles delivery in a complex vascular
      networks is very challenging because it involves interplay of transport,
      hydrodynamic force, and multivalent interactions across different scales.
      Heterogeneous pulmonary network includes up to 16 generations of vessels in its
      arterial tree. Modeling the complete pulmonary vascular system in 3D is
      computationally unrealistic. To save computational cost, a model reconstructed
      from MRI scanned images is cut into an arbitrary pathway consisting of the upper
      4-generations. The remaining generations are represented by an artificially
      rebuilt pathway. Physiological data such as branch information and connectivity
      matrix are used for geometry reconstruction. A lumped model is used to model the
      flow resistance of the branches that are cut off from the truncated pathway.
      Moreover, since the nanoparticle binding process is stochastic in nature, a
      binding probability function is used to simplify the carrier attachment and
      detachment processes. The stitched realistic and artificial geometries coupled
      with the lumped model at the unresolved outlets are used to resolve the flow
      field within the truncated arterial tree. Then, the biodistribution of 200nm,
      700nm and 2um particles at different vessel generations is studied. At the end,
      0.2-0.5% nanocarrier deposition is predicted during one time passage of drug
      carriers through pulmonary vascular tree. Our truncated approach enabled us to
      efficiently model hemodynamics and accordingly particle distribution in a complex
      3D vasculature providing a simple, yet efficient predictive tool to study drug
      delivery at organ level.

PMID- 27863745
TI  - A Systematic Review of Voice Therapy: What "Effectiveness" Really Implies.
AB  - INTRODUCTION: Behavioral voice therapy guided by a speech-language pathologist is
      recommended as the main treatment approach for many kinds of voice disorders.
      Encouraging evidence regard of good outcomes from voice therapy has been found in
      two previous reviews on broad patient populations. However, no definitive
      conclusion on the effectiveness of direct voice therapy can be drawn from these
      reviews due to limitations of the included studies. AIMS: To review recent
      literature on voice therapy; to provide clinicians with a list of evidence-based
      voice therapy techniques; to incorporate the therapy components in a
      physiologically based model; to assess the limitations and progress achieved in
      the recent research on voice therapy. METHODS: A literature search was conducted
      using three electronic databases: PubMed, Scopus, and CINAHL. A similar strategy
      was used in all three databases to highlight the concepts of "therapy" and "voice
      disorders." Only randomized controlled trials were included in the review.
      RESULTS: Fifteen papers met the inclusion criteria, covering five categories of
      voice disorders (functional, Parkinson induced, GERD induced, presbyphonia,
      unilateral vocal fold paresis) and seven specific behavioral voice therapy
      approaches. Statistically significant improvements were found postintervention on
      at least one outcome variable in all but one study. Clinical significance of the
      results was rarely discussed. Discrepancies in reported outcome measures were
      found across studies, making comparisons between interventions challenging.
      CONCLUSION: Behavioral voice therapy generally leads to significant improvements
      in voice outcomes, but further research considering clinical meaningfulness of
      the results are needed to establish what is really meant by the term
      "effectiveness" when it comes to voice therapy.

PMID- 27863744
TI  - Towards the improved quantification of in vivo abnormal wall shear stresses in
      BAV-affected patients from 4D-flow imaging: Benchmarking and application to real
      data.
AB  - Bicuspid aortic valve (BAV), i.e. the fusion of two aortic valve cusps, is the
      most frequent congenital cardiac malformation. Its progression is often
      characterized by accelerated leaflet calcification and aortic wall dilation.
      These processes are likely enhanced by altered biomechanical stimuli, including
      fluid-dynamic wall shear stresses (WSS) acting on both the aortic wall and the
      aortic valve. Several studies have proposed the exploitation of 4D-flow magnetic
      resonance imaging sequences to characterize abnormal in vivo WSS in BAV-affected
      patients, to support prognosis and timing of intervention. However, current
      methods fail to quantify WSS peak values. On this basis, we developed two new
      methods for the improved quantification of in vivo WSS acting on the aortic wall
      based on 4D-flow data. We tested both methods separately and in combination on
      synthetic datasets obtained by two computational fluid-dynamics (CFD) models of
      the aorta with healthy and bicuspid aortic valve. Tests highlighted the need for
      data spatial resolution at least comparable to current clinical guidelines, the
      low sensitivity of the methods to data noise, and their capability, when used
      jointly, to compute more realistic peak WSS values as compared to state-of-the
      art methods. The integrated application of the two methods on the real 4D-flow
      data from a preliminary cohort of three healthy volunteers and three BAV-affected
      patients confirmed these indications. In particular, quantified WSS peak values
      were one order of magnitude higher than those reported in previous 4D-flow
      studies, and much closer to those computed by highly time- and space-resolved CFD
      simulations.

PMID- 27863746
TI  - Biophysical skin properties of grade 1 pressure ulcers and unaffected skin in
      spinal cord injured and able-bodied persons in the unloaded sacral region.
AB  - AIM OF THE STUDY: To examine biophysical skin properties in the sacral region in
      spinal cord injury (SCI) patients suffering from a grade 1 pressure ulcer (PU)
      defined as non-blanchable erythema (SCI/PU), SCI patients in the post-acute phase
      (SCI/PA) and able-bodied participants (CON). Also, for SCI/PU patients, both the
      affected skin and healthy skin close to the PU were examined. STUDY DESIGN: An
      experimental controlled study with a convenience sample. SETTING: A Swiss acute
      care and rehabilitation clinic specializing in SCIs. MATERIALS AND METHODS: We
      determined hydration, redness, elasticity and perfusion of the unloaded skin in
      the sacral region of 6 SCI/PU patients (affected and healthy skin), 20 SCI/PA
      patients and 10 able-bodied controls. These measures were made by two trained
      examiners after the patients were lying in the supine position. RESULTS: The
      affected skin of SCI/PU patients showed elevated redness: median 595.5 arbitrary
      units (AU) (quartiles 440.4; 631.6) and perfusion: 263.0 AU (104.1; 659.4), both
      significantly increased compared to the healthy skin in SCI/PA patients and CON
      (p < 0.001). Similarly, healthy skin of SCI/PA patients showed elevated redness
      (p = 0.016) and perfusion (p < 0.001) compared to CON. On the other hand,
      differences in redness and perfusion between the affected and unaffected skin in
      SCI/PU patients were not significant. The results for skin hydration and skin
      elasticity were similar in all groups. CONCLUSIONS: Skin perfusion and redness
      were significantly increased in grade 1 PUs and for healthy skin in both SCI/PA
      patients and CON participants; thus, these are important in understanding the
      pathophysiology of PUs and skin in SCI.

PMID- 27863747
TI  - Symmetrical aryl linked bis-iminothiazolidinones as new chemical entities for the
      inhibition of monoamine oxidases: Synthesis, in vitro biological evaluation and
      molecular modelling analysis.
AB  - The multifactorial nature of Parkinson's disease necessitates the development of
      new chemical entities with inherent ability to address key pathogenic processes.
      To this end, two series of new symmetrical 1,2- and 1,4-bis(2-aroyl/alkoylimino-5
      (2-methoxy-2-oxoethylidene)-4-oxo-thiazolidin-3-yl)benzene derivatives (3a-g and
      5a-e) were synthesized in good yields by the cyclization of 1,2- and 1,4-bis(N'
      substituted thioureido)benzene intermediates with dimethyl acetylenedicarboxylate
      (DMAD) in methanol at ambient temperature. The bis-iminothiazolidinone compounds
      were investigated in vitro for their inhibition of monoamine oxidase (MAO-A & MAO
      B) enzymes with the aim to identify new and distinct pharmacophores for the
      treatment of neurodegenerative disorders like Parkinson's disease. Most of the
      designed compounds exhibited good inhibitory efficacy against monoamine oxidases.
      Compound 5a was identified as the most potent inhibitor of MAO-A depicting an
      IC50 value of 0.001MUM, a 4-fold stronger inhibitory strength compared to
      standard inhibitor (clorgyline: IC50=0.0045MUM). Molecular docking studies
      provided insights into enzyme-inhibitor interactions and a rationale for the
      observed inhibition towards monoamine oxidases.

PMID- 27863749
TI  - Emerging issues on hepatitis C virus infection after the introduction of the
      Directly Acting Antivirals.

PMID- 27863750
TI  - Tribute to 100 years of Professor Dr. Michel Abu Jamra.

PMID- 27863748
TI  - Ethyl nitrobenzoate: A novel scaffold for cholinesterase inhibition.
AB  - A series of novel cholinesterase inhibitors containing nitrobenzoate core
      structure were synthesized by a facile and efficient method. The structure of the
      novel compounds were fully characterized and confirmed by analytical as well as
      spectroscopic methods. Compound indicated as 2f was found to possess the best
      cholinesterase inhibitory activities of all the evaluated compounds. Results
      suggest that 2f is a selective acetylcholinesterase inhibitor, although it also
      inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition
      result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In
      addition, it was found to have low cytotoxicity. Molecular docking on compound 2f
      was carried out to rationalize the observed in vitro enzymatic assay results.
      Most importantly, the potential of nitrobenzoate derivatives as cholinesterase
      inhibitor was shown through this study. In summary, we discovered nitrobenzoates
      as a new scaffold that may eventually yield useful compounds in treatment of
      Alzheimer's disease.

PMID- 27863751
TI  - New developments in the understanding and diagnosis of myelodysplastic syndromes
      with ring sideroblasts.

PMID- 27863752
TI  - Hematopoietic stem cell mobilization for autologous transplantation in multiple
      myeloma patients previously exposed to cyclophosphamide, thalidomide, and
      dexamethasone: is granulocyte-colony stimulating factor alone enough?

PMID- 27863753
TI  - Platelet and reticulocyte new parameters: why and how to use them?

PMID- 27863754
TI  - Survival and treatment response in adults with acute promyelocytic leukemia
      treated with a modified International Consortium on Acute Promyelocytic Leukemia
      protocol.
AB  - Acute promyelocytic leukemia has good prognosis in view of the high complete
      remission and survival rates achieved with therapies containing all-trans
      retinoic acid or arsenic trioxide. However, there is a significant risk of death
      during induction due to hemorrhage secondary to disseminated intravascular
      coagulation. This has contributed to a gap in the prognosis of patients between
      developed and developing countries. The International Consortium on Acute
      Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol
      based on daunorubicin and all-trans retinoic acid stratified by risk geared
      toward developing countries. Herein are presented the results from the first
      patient cohort treated in a single developing country hospital employing a
      slightly modified version of the International Consortium protocol in a real life
      setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8%
      had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission
      rate was 94.4% after a median of 42 days. Both relapse rates and death rates were
      one patient (5.5%) each. No deaths were observed during consolidation. After a
      median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and
      safety of the International Consortium on Acute Promyelocytic Leukemia protocol
      has been reproduced in acute promyelocytic leukemia patients from a developing
      country.

PMID- 27863756
TI  - Herpes zoster after autologous hematopoietic stem cell transplantation.
AB  - BACKGROUND: The autologous hematopoietic stem cell transplantation procedure
      involves immunosuppression of the patient. Thus, the patient has an elevated risk
      for several diseases, such as infections with the varicella-zoster virus.
      Prevention protocols have been proposed based on the use of acyclovir from the
      first day of conditioning, and maintaining this drug for 30-100 days after the
      procedure or for as much as one year. The objective of this work was to evaluate
      the incidence of herpes zoster after autologous transplantations related to the
      early suspension of acyclovir. METHODS: A retrospective study was carried out
      based on the collection of data from 231 medical records of transplant patients
      in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade
      Federal de Juiz de Fora in the period between 2004 and 2014. RESULTS: Fourteen
      (6.1%) patients had herpes zoster in the post-transplant period on average within
      six months of the procedure. Patients with multiple myeloma (64.3%) were the most
      affected. There was a statistically significant difference in the age of the
      patients, with older individuals having a greater chance of developing the
      infection (p-value=0.002). There were no significant differences for the other
      variables analyzed. CONCLUSION: The early suspension of acyclovir can be safe in
      patients who receive autologous hematopoietic stem cell transplants. However some
      groups may benefit from extended prophylaxis with acyclovir, particularly older
      patients and patients with multiple myeloma.

PMID- 27863755
TI  - Identification of the MYST3-CREBBP fusion gene in infants with acute myeloid
      leukemia and hemophagocytosis.
AB  - BACKGROUND: Acute myeloid leukemia presenting the MYST3-CREBBP fusion gene is a
      rare subgroup associated with hemophagocytosis in early infancy and monocytic
      differentiation. The aim of this study was to define the relevant molecular
      cytogenetic characteristics of a unique series of early infancy acute myeloid
      leukemia cases (<=24months old), based on the presence of hemophagocytosis by
      blast cells at diagnosis. METHODS: A series of 266 infant cases of acute myeloid
      leukemia was the reference cohort for the present analysis. Acute myeloid
      leukemia cases with hemophagocytosis by blast cells were reviewed to investigate
      the presence of the MYST3-CREBBP fusion gene by fluorescence in situ
      hybridization (FISH) and reverse transcription polymerase chain reaction.
      RESULTS: Eleven cases with hemophagocytosis were identified with hemophagocytic
      lymphohistiocytosis being ruled out. Six cases were classified as myelomonocytic
      leukemia, three as AML-M7 and two as AML-M2. In five cases, the presence of the
      MYST3-CREBBP fusion gene identified by molecular cytogenetics was confirmed by
      fluorescence in situ hybridization. All patients received treatment according to
      the Berlin-Frankfurt-Munster acute myeloid leukemia protocols and only one out of
      the five patients with the MYST3-CREBBP fusion gene is still alive. CONCLUSIONS:
      Our findings demonstrate that the presence of hemophagocytosis in acute myeloid
      leukemia was not exclusively associated to the MYST3-CREBBP fusion gene.
      Improvements in molecular cytogenetics may help to elucidate more complex
      chromosomal rearrangements in infants with acute myeloid leukemia and
      hemophagocytosis.

PMID- 27863757
TI  - Is it feasible to use granulocyte-colony stimulating factor alone to mobilize
      progenitor cells in multiple myeloma patients induced with a cyclophosphamide,
      thalidomide and dexamethasone regimen?
AB  - BACKGROUND: Cyclophosphamide plus thalidomide as induction for multiple myeloma
      patients eligible for autologous stem cell transplantation may be a limiting
      factor for cell mobilization. The minimum acceptable mobilized peripheral blood
      stem cell count to prevent deleterious effects during transplantation is 2.0*106
      CD34+ cells/kg. Combining other treatments to granulocyte-colony stimulating
      factor, such as cyclophosphamide, could overcome the mobilization limitation. The
      objective of this study was to assess the number of CD34+ cells mobilized using
      granulocyte-colony stimulating factor with and without cyclophosphamide after
      induction with cyclophosphamide, thalidomide and dexamethasone. METHODS: A
      retrospective study was performed of a cohort of multiple myeloma patients
      submitted to autologous stem cell transplantations at two Brazilian centers
      between May 2009 and July 2013. The oral cyclophosphamide and thalidomide
      induction doses used were 1500mg/month and 100-200mg/day, respectively.
      Mobilization doses were 10-15mcg/kg granulocyte-colony stimulating factor with 2
      4g/m2 cyclophosphamide, or 15-20mcg/kg granulocyte-colony stimulating factor
      alone for 5 days. Collection of >2.0*106 CD34+ cells/kg was considered
      sufficient. RESULTS: Eighty-eight patients were analyzed; only 18 received
      cyclophosphamide. The median age was 58 years old (range: 51-62) for the
      granulocyte-colony stimulating factor group and 56.5 years old (range: 54-60) for
      granulocyte-colony stimulating factor plus cyclophosphamide group. Fifty-two
      patients were male. Eighty cases (90.9%) were Durie-Salmon Staging System III-A/B
      and 38 (44.7%) and 20 cases (23.5%) were International Staging System 2 and 3,
      respectively. The group that received cyclophosphamide collected a higher median
      number of progenitor cells [3.8 (range: 3.1-4.4) vs. 3.2 (range: 2.3-3.8)] (p
      value=0.008). No correlation was observed between better responses or number of
      induction cycles and the number of cells collected. CONCLUSION: The number of
      cells mobilized with granulocyte-colony stimulating factor plus cyclophosphamide
      was higher. However, in both groups, the median number of CD34+ cells was
      sufficient to perform a single autologous stem cell transplantation; no
      deleterious effects were reported during harvesting.

PMID- 27863758
TI  - Determination of reference ranges for immature platelet and reticulocyte
      fractions and reticulocyte hemoglobin equivalent.
AB  - INTRODUCTION: The immature platelet and immature reticulocyte fractions represent
      the ratios of platelets and reticulocytes recently released into the circulation
      and thus with higher RNA content. They are considered early indicators of bone
      marrow recovery. OBJECTIVE: The aim of this study was to determine the reference
      ranges for the immature platelet and reticulocyte fractions of hematologically
      normal individuals in a university hospital. METHODS: Venous blood samples
      collected in ethylenediaminetetraacetic acid K3 were analyzed using a Sysmex XE
      5000TM analyzer. Individuals with platelet and reticulocyte counts within the
      reference ranges, and a blood count within the laboratory's screening criteria
      were included. Individuals with clinical conditions that could affect
      hematological results were excluded. The immature platelet fraction, high, medium
      and low fluorescence reticulocyte fractions and reticulocyte hemoglobin
      equivalent were evaluated. The reference ranges were determined according to the
      recommendations of the International Federation of Clinical Chemistry. RESULTS:
      One hundred and thirty-two outpatients were evaluated. The mean age was 44 years
      (range: 13-80 years), 72 (54.5%) were women treated in a university hospital. The
      mean platelet count was 250.8*109/L and the mean reticulocyte count was
      0.052*109/L. The following reference ranges were obtained: immature reticulocyte
      fraction 1.6-12.1%, the high, medium and low fluorescence reticulocyte fractions
      were 0.0-1.7%, 1.6-11.0% and 87.9-98.4%, respectively, the reticulocyte
      hemoglobin equivalent was 30.0-37.6% and immature platelet fraction was 0.8-5.6%.
      There was a statistically significant difference (p-value=0.006) between genders
      in respect to the immature platelet fraction with 0.8-4.7% for females and 0.7
      6.1% for males. The immature reticulocyte fraction was directly correlated with
      the reticulocyte count. CONCLUSION: Determining the reference range is critical
      to the introduction of a new parameter. The reference ranges obtained herein
      corroborate those reported in previous publications and will contribute to the
      clinical and laboratory application of the indices.

PMID- 27863759
TI  - Outcomes of allogeneic hematopoietic stem cell transplantation for lymphomas: a
      single-institution experience.
AB  - INTRODUCTION: Allogeneic hematopoietic stem cell transplantation offers the
      opportunity for extended survival in patients with Hodgkin's and non-Hodgkin
      lymphomas who relapsed after, or were deemed ineligible for, autologous
      transplantation. This study reports the cumulative experience of a single center
      over the past 14 years aiming to define the impact of patient, disease, and
      transplant-related characteristics on outcomes. METHODS: All patients with
      histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who
      received allogeneic transplantation from 2000 to 2014 were retrospectively
      studied. RESULTS: Forty-one patients were reviewed: 10 (24%) had Hodgkin's and 31
      (76%) had non-Hodgkin lymphomas. The median age was 50 years and 23 (56%) were
      male. The majority of patients (68%) had had a prior autologous transplantation.
      At the time of allogeneic transplantation, 18 (43%) patients were in complete and
      seven (17%) were in partial remission. Most (95%) patients received reduced
      intensity conditioning, 49% received matched sibling donor grafts, 24% matched
      unrelated donor grafts, and 27% received double umbilical cord blood grafts. The
      100-day treatment-related mortality rate was 12%. After a median duration of
      follow up of 17.1 months, the median progression-free and overall survival was
      40.5 and 95.8 months, respectively. On multivariate analysis, patients who had
      active disease at the time of transplant had inferior survival. CONCLUSIONS:
      Allogeneic transplantation results extend survival in selected patients with
      relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment
      related mortality. Patients who have active disease at the time of allogeneic
      transplantation have poor outcomes.

PMID- 27863760
TI  - Splicing factor SF3B1 mutations and ring sideroblasts in myelodysplastic
      syndromes: a Brazilian cohort screening study.
AB  - BACKGROUND: Myelodysplastic syndromes (MDS) comprise a group of malignant clonal
      hematologic disorders characterized by ineffective hematopoiesis and propensity
      for progression to acute myeloid leukemia. Acquired mutations in the gene
      encoding RNA splicing factor 3B subunit 1 (SF3B1) are highly associated with the
      MDS subtypes presenting ring sideroblasts, and represent a specific nosological
      entity. The effects of these mutations on clinical outcomes are diverse and
      contrasting. METHODS: A cohort of 91 Brazilian MDS patients, including patients
      with ring sideroblasts in the bone marrow, were screened for mutations in the
      SF3B1 hotspots (exons 12-15) by direct Sanger sequencing. RESULTS: SF3B1
      heterozygous mutations were identified in six patients (7%), all of them with
      ring sideroblasts, thus confirming the association between SF3B1 mutations and
      myelodysplastic syndrome subtypes bearing this morphologic feature (frequency of
      6/13, p-value<0.0001). CONCLUSION: This is the first screening of SF3B1 mutations
      in a cohort of Brazilian myelodysplastic syndrome patients. Our findings confirm
      that mutations in this splicing gene correlate with bone marrow ringed
      sideroblasts.

PMID- 27863761
TI  - Iron deficiency in cancer patients.
AB  - Anemia is a frequent complication in cancer patients, both at diagnosis and
      during treatment, with a multifactorial etiology in most cases. Iron deficiency
      is among the most common causes of anemia in this setting and can develop in
      nearly half of patients with solid tumors and hematologic malignancies.
      Surprisingly, this fact is usually neglected by the attending physician in a way
      that proper and prompt investigation of the iron status is either not performed
      or postponed. In cancer patients, functional iron deficiency is the predominant
      mechanism, in which iron availability is reduced due to disease or the therapy
      related inflammatory process. Hence, serum ferritin is not reliable in detecting
      iron deficiency in this setting, whereas transferrin saturation seems more
      appropriate for this purpose. Besides, lack of bioavailable iron can be further
      worsened by the use of erythropoiesis stimulating agents that increase iron
      utilization in the bone marrow. Iron deficiency can cause anemia or worsen pre
      existing anemia, leading to a decline in performance status and adherence to
      treatment, with possible implications in clinical outcome. Due to its frequency
      and importance, treatment of this condition is already recommended in many
      specialty guidelines and should be performed preferably with intravenous iron.
      The evidences regarding the efficacy of this treatment are solid, with response
      gain when combined with erythropoiesis stimulating agents and significant
      increments in hemoglobin as monotherapy. Among intravenous iron formulations,
      slow release preparations present more favorable pharmacological characteristics
      and efficacy in cancer patients.

PMID- 27863762
TI  - Structural diversity and biological importance of ABO, H, Lewis and secretor
      histo-blood group carbohydrates.
AB  - ABO, H, secretor and Lewis histo-blood system genes control the expression of
      part of the carbohydrate repertoire present in areas of the body occupied by
      microorganisms. These carbohydrates, besides having great structural diversity,
      act as potential receptors for pathogenic and non-pathogenic microorganisms
      influencing susceptibility and resistance to infection and illness. Despite the
      knowledge of some structural variability of these carbohydrate antigens and their
      polymorphic levels of expression in tissue and exocrine secretions, little is
      known about their biological importance and potential applications in medicine.
      This review highlights the structural diversity, the biological importance and
      potential applications of ABO, H, Lewis and secretor histo-blood carbohydrates.

PMID- 27863763
TI  - Guidelines on Beta-thalassemia major - regular blood transfusion therapy:
      Associacao Brasileira de Hematologia, Hemoterapia e Terapia Celular: project
      guidelines: Associacao Medica Brasileira - 2016.

PMID- 27863766
TI  - A closer look into blood group discrepancy arising due to an underlying
      malignancy.

PMID- 27863765
TI  - A clinical challenge: Treatment of acute myeloid leukemia in a Jehovah's Witness.

PMID- 27863767
TI  - Stroke-like encephalopathy following high-dose intravenous methotrexate in an
      adolescent with osteosarcoma: a case report.

PMID- 27863769
TI  - Erratum to "Frequencies of polymorphisms of Rh, Kell, Kidd, Duffy and Diego
      systems of Santa Catarina, southern Brazil" [Rev Bras Hematol Hemoter.
      2016;38(3):199-205].

PMID- 27863764
TI  - Diagnosis and treatment of chronic lymphocytic leukemia: recommendations from the
      Brazilian Group of Chronic Lymphocytic Leukemia.
AB  - Chronic lymphocytic leukemia is characterized by clonal proliferation and
      progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+
      and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood,
      lymph nodes, and spleen. The diagnosis is established by immunophenotyping
      circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai
      and Binet) established by physical examination and blood counts, as well as by
      several biological and genetic markers. In this update, we present the
      recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the
      diagnosis and treatment of chronic lymphocytic leukemia. The following
      recommendations are based on an extensive literature review with the aim of
      contributing to more uniform patient care in Brazil and possibly in other
      countries with a similar social-economic profile.

PMID- 27863768
TI  - Differential profile of CDKN1A and TP53 expressions in bone marrow mesenchymal
      stromal cells from myeloid neoplasms.

PMID- 27863770
TI  - Chimney, periscope, or snorkel technique to relieve dysphagia.

PMID- 27863771
TI  - Selection of emission factor standards for estimating emissions from diesel
      construction equipment in building construction in the Australian context.
AB  - Emissions from equipment usage and transportation at the construction stage are
      classified as the direct emissions which include both greenhouse gas (GHG) and
      non-GHG emissions due to partial combustion of fuel. Unavailability of a reliable
      and complete inventory restricts an accurate emission evaluation on construction
      work. The study attempts to review emission factor standards readily available
      worldwide for estimating emissions from construction equipment. Emission factors
      published by United States Environmental Protection Agency (US EPA), Australian
      National Greenhouse Accounts (AUS NGA), Intergovernmental Panel on Climate Change
      (IPCC) and European Environmental Agency (EEA) are critically reviewed to
      identify their strengths and weaknesses. A selection process based on the
      availability and applicability is then developed to help identify the most
      suitable emission factor standards for estimating emissions from construction
      equipment in the Australian context. A case study indicates that a fuel based
      emission factor is more suitable for GHG emission estimation and a time based
      emission factor is more appropriate for estimation of non-GHG emissions. However,
      the selection of emission factor standards also depends on factors like the place
      of analysis (country of origin), data availability and the scope of analysis.
      Therefore, suitable modifications and assumptions should be incorporated in order
      to represent these factors.

PMID- 27863773
TI  - Simulating the environmental performance of post-harvest management measures to
      comply with the EU Nitrates Directive.
AB  - Nitrate (NO3-) leaching from farmland remains the predominant source of nitrogen
      (N) loads to European ground- and surface water. As soil mineral N content at
      harvest is often high and may increase by mineralisation from crop residues and
      soil organic matter, it is critical to understand which post-harvest management
      measures can be taken to restrict the average NO3- concentration in ground- and
      surface waters below the norm of 50 mg l-1. Nitrate leaching was simulated with
      the EU-rotate_N model on a silty and a sandy soil following the five main arable
      crops cultivated in Flanders: cut grassland, silage maize, potatoes, sugar beets
      and winter wheat, in scenarios of optimum fertilisation with and without post
      harvest measures. We compared the average NO3- concentration in the leaching
      water at a depth of 90 cm in these scenarios after dividing it by a factor of 2.1
      to include natural attenuation processes occurring during transport towards
      ground- and surface water. For cut grassland, the average attenuated NO3-
      concentration remained below the norm on both soils. In order to comply with the
      Nitrates Directive, post-harvest measures seemed to be necessary on sandy soils
      for the four other crops and on silty soils for silage maize and for potatoes.
      Successful measures appeared to be the early sowing of winter crops after
      harvesting winter wheat, the undersowing of grass in silage maize and the removal
      of sugar beet leaves. Potatoes remained a problematic crop as N uptake by winter
      crops was insufficient to prevent excessive NO3- leaching. For each crop, maximum
      levels of soil mineral N content at harvest were proposed, both with and without
      additional measures, which could be used in future nutrient legislation. The
      approach taken here could be upscaled from the field level to the subcatchment
      level to see how different crops could be arranged within a subcatchment to
      permit the cultivation of problem crops without adversely affecting the water
      quality in such a subcatchment.

PMID- 27863772
TI  - The evolution of crop cultivation and paleoenvironment in the Longji Terraces,
      southern China: Organic geochemical evidence from paleosols.
AB  - The Longji ancient agricultural terraces in the Longji Mountain area (Guilin,
      southern China), which still remain in use, are famous for their magnificent
      terraced landscape with a mix of ecosystem and human inhabitation. Previous
      research has revealed the genesis and preliminary paleoenvironmental record of
      the agricultural terraces, but little is known about variations in crop
      cultivation over time. In this study, organic geochemical analyses and
      radiocarbon dating of an aggradational cultivated soil from a terrace profile
      were used to explore crop type variation and relevant paleoenvironmental change
      during the period of cultivation on the Longji Terraces. Hydroponic farming with
      rice (C3) planting has been the dominant cultivation mode since the initial
      construction of the terraces. Warm-dry climate contributed to the growth of
      drought-tolerant crop (C4) cultivation in the late 15th century. Temperature
      deterioration during the Little Ice Age had a negative impact on dry and
      hydroponic farming activities from the late 15th century to the late 19th
      century, while climate warming after the Little Ice Age promoted the
      redevelopment of hydroponic farming.

PMID- 27863774
TI  - [Women's knowledge of folic acid].
AB  - Many trials have shown that folic acid supplementation before and during
      pregnancy reduces the risk of neural tube defects in general population. We
      investigated the knowledge of folic acid in women of child-bearing age. Women of
      child-bearing age were interviewed by 20 pharmacists living in Haute-Garonne
      between January and February 2014. One hundred ninety-six women were included in
      the present study. Out of them, 36% of women never heard of folic acid and 82%
      were not aware of its benefits. Knowledge was higher in older women, women in a
      couple and women with higher educational level (P<10-2). This study underlines
      that women are not enough aware of benefits of folic acid during pregnancy.
      Moreover, previous studies have shown that French women have low use of folic
      acid during peri-conceptional period. Information of general population will be
      required for a better prevention of folic acid-preventable NTDs.

PMID- 27863775
TI  - Operation for insulinomas in multiple endocrine neoplasia type 1: When
      pancreatoduodenectomy is appropriate.
AB  - BACKGROUND: Distal pancreatectomy is the most frequent operation for insulinomas
      complicating multiple endocrine neoplasia type 1 insulinoma, although there are
      conditions for which a different operative approach might be preferable. In this
      article, we report the operative experience of a referral center for multiple
      endocrine neoplasia type 1 insulinoma. METHODS: Twelve patients underwent
      operations between 1992 and 2015: 8 underwent a distal pancreatic resection, and
      4 underwent a pancreatoduodenectomy. Enucleation of other macroadenomas present
      in the remnant pancreas was performed in 9 out of these 12 patients. RESULTS:
      Operative complications (2 pancreatic fistulas and 2 cases of pancreatitis)
      occurred in 4 of the 8 distal pancreatic resections. In 1 patient, reoperation
      was required to resolve the complications of the first operation. At pathologic
      analysis, multiple insulinomas were found in 5 patients, lymph-nodal metastasis
      positive for insulin in 2 patients, multiple nonfunctioning pancreatic tumors in
      all patients, glucagonoma in 4 patients, and gastrinoma in the duodenum or lymph
      nodes in 4 patients. All the patients were treated successfully for the
      hypoglycemic/hyperinsulinemic syndrome with no clinical recurrence at a mean
      follow-up of 85 months (range 4-242 months). Recurrent nonfunctioning pancreatic
      tumor macroadenomas in the remnant pancreas occurred in only 1 of the 12
      patients, and no progression of the gastrinomas was observed. None of the
      patients developed diabetes mellitus. CONCLUSION: Resection of the most severely
      affected part of the pancreas, whether left or right, associated with enucleation
      of concomitant macroadenomas in the preserved pancreas is recommended for the
      treatment of hypoglycemic/hyperinsulinemic syndrome and to prevent malignant
      progression of nonfunctioning pancreatic tumors in patients with multiple
      endocrine neoplasia type 1. If the head of the pancreas is the most affected site
      and the Zollinger-Ellison syndrome is concomitant, then pancreatoduodenectomy
      should be preferred over distal pancreatectomy.

PMID- 27863776
TI  - Parathyroidectomy prior to kidney transplant decreases graft failure.
AB  - BACKGROUND: Uncorrected uremic hyperparathyroidism is associated with delayed
      graft function after kidney transplantation. The current guidelines of the Kidney
      Disease Improving Global Outcomes recommend maintaining parathyroid hormone <=9x
      normal in patients pre-kidney transplantation. This study explores the effect of
      increased levels of serum parathyroid hormone and preoperative parathyroidectomy
      on outcomes after kidney transplantation. METHODS: A retrospective review was
      performed of adult patients who underwent kidney transplantation between January
      1, 2005, and December 31, 2014, at a single institution. Biochemistries and
      outcomes were analyzed pre-kidney transplantation and at 30 days, 6 months, and 1
      year post-kidney transplantation. RESULTS: A total of 913 patients underwent
      kidney transplantation from 2005-2014. Graft survival 1 year post-kidney
      transplantation was 97.8%. Overall, 462 (50.6%) patients had a pre-kidney
      transplantation diagnosis of uncorrected uremic hyperparathyroidism, which was
      associated with complications in the first year post-kidney transplantation (odds
      ratio 1.44; 95% confidence interval, 1.11-1.87); no statistical association with
      delayed graft function or graft failure was detected. Pre-kidney transplantation
      parathyroid hormone >=6x normal was associated with post-kidney transplantation
      graft failure (P < .05). A total of 57 (6.2%) patients underwent pre-kidney
      transplantation parathyroidectomy, which was associated with lesser risk of graft
      failure (odds ratio: 0.547; 95% confidence interval, 0.327-0.913), but no
      statistically significant association with delayed graft function or
      complications were detected. CONCLUSION: Pre-kidney transplantation
      parathyroidectomy decreases post-kidney transplantation graft failure and may
      benefit patients whose serum parathyroid hormone levels decrease into the target
      range of current Kidney Disease Improving Global Outcomes guidelines.

PMID- 27863777
TI  - Concentration of serum calcium is not correlated with symptoms or severity of
      primary hyperparathyroidism: An examination of 20,081 consecutive adults.
AB  - BACKGROUND: Guidelines for operative treatment of primary hyperparathyroidism
      include calcium levels >1 mg/dL above normal. We sought to determine whether
      greater calcium concentrations were associated with increased symptoms or disease
      severity. METHODS: A retrospective review of a prospectively maintained database
      of adults undergoing parathyroidectomy for primary hyperparathyroidism, grouped
      according to greatest preoperative calcium level: those patients with calcium
      concentrations between 10.0 and 11.0 mg/dL and those with >11.0 mg/dL. We
      compared subjective symptoms and objective measures of disease severity. RESULTS:
      The review included 20,081 adults who were split nearly evenly between calcium
      concentrations between 10.0 and 11.0 (10,430, 51.9%) and those with >11.0 mg/dL
      (9,651, 48.1%). In both groups, an absence of symptoms related to primary
      hyperparathyroidism was uncommon (<5%). All subjective and objective measures of
      disease severity were nearly identical with no significant differences
      (percentages for calcium concentrations between 10.0 and 11.0 and those with
      >11.0 mg/dL, respectively), including fatigue (72% for both groups), heartburn
      (37% vs 34%), bone pain (50% vs 48%), sleep disturbances (68% vs 65%),
      osteoporosis (40% in both groups), kidney stones (21% vs 22%), chronic kidney
      disease with glomerular filtration rate <60 (29% vs 32%), and hypertension (50%
      vs 53%). CONCLUSION: Serum calcium concentrations of greater than or less than 11
      mg/dL are unrelated to symptoms and disease severity in primary
      hyperparathyroidism. There is no evidence to support a serum calcium threshold in
      parathyroidectomy guidelines.

PMID- 27863778
TI  - Discussion.

PMID- 27863779
TI  - How long should we follow patients after apparently curative parathyroidectomy?
AB  - BACKGROUND: Little is known about the long-term recurrence risk for primary
      hyperparathyroidism after immediately "curative" parathyroidectomy. This study
      aimed to evaluate the risk of recurrent hyperparathyroidism in the 10 years after
      operation. METHOD: We retrospectively identified patients with sporadic primary
      hyperparathyroidism undergoing initial parathyroidectomy between November 1, 2000
      and June 30, 2005. Recurrence was defined as serum calcium >10.2 mg/dL after 6
      months from operation. Kaplan-Meier estimates and Cox proportional hazards were
      used to evaluate disease-free survival and predictors of recurrence. RESULTS: We
      evaluated 196 patients with a 14.8% 10-year recurrence rate. Median time to
      recurrence was 6.3 years (interquartile range 3.4-10.8 years), and 34.5% of all
      recurrences were identified >10 years after operation. There was no difference in
      recurrence between open and minimally invasive operation (P = .448). Double
      adenomas (P = .006), intraoperative parathyroid hormone drop <70% (P = .015), and
      young age (P = .032) were predictive of disease recurrence. Multivariable
      analysis demonstrated that older age was protective against recurrence (hazard
      ratio 0.97, 95% confidence interval 0.94-0.99, P = .034), while double adenomas
      (hazard ratio 3.52, 95% confidence interval 1.23-10.08, P = .019) were an
      independent predictor for recurrence. CONCLUSION: The long-term recurrence rate
      for sporadic primary hyperparathyroidism after "curative" parathyroidectomy is
      likely greater than reported. With over one-third of our institutional
      recurrences at >10 years after the initial operation, long-term follow-up is
      essential.

PMID- 27863781
TI  - Discussion.

PMID- 27863782
TI  - Discussion.

PMID- 27863780
TI  - Identification of primary tumors in patients presenting with metastatic
      gastroenteropancreatic neuroendocrine tumors.
AB  - BACKGROUND: Patients with gastroenteropancreatic neuroendocrine tumors often
      present with metastases. Identification of the primary tumor is important for
      operative management, and therefore we sought to determine our success at
      identifying primary tumors with diagnostic testing and operative exploration.
      METHODS: A clinical neuroendocrine tumor database was reviewed to identify
      patients presenting with metastases and primary tumor in situ. Results of
      radiologic, endoscopic, and operative procedures were evaluated to determine
      which correctly identified the primary tumor. RESULTS: There were 197 patients
      presenting with metastases and unresected primaries, 134 who had an operation and
      63 managed nonoperatively. Primaries were identified preoperatively in 168 (84%),
      at operative exploration in 7, and were not found in 22 patients. Computed
      tomography found 150/197 primary tumors, somatostatin-receptor scintigraphy
      88/155, and endoscopy 43/107. The sensitivity of computed tomography surpassed
      scintigraphy (76% vs 57%, P < .01). The primary was removed in 130/134 (97%)
      patients, and hepatic debulking was performed in 67%. Median survival for
      operative patients with small bowel and pancreatic tumors was 145 and 71 months,
      respectively. CONCLUSION: Imaging and endoscopy identified the primary tumor in
      most patients, and the majority of the others were found at exploration.
      Preoperative testing facilitated operative planning, allowing for resection of
      the primary and hepatic debulking in most patients.

PMID- 27863783
TI  - Discussion.

PMID- 27863784
TI  - Discussion.

PMID- 27863785
TI  - Discussion.

PMID- 27863786
TI  - Preoperative detection of RAS mutation may guide extent of thyroidectomy.
AB  - BACKGROUND: Preoperative detection of RAS mutations can contribute to cancer risk
      assessment in indeterminate thyroid nodules, although RAS is not always
      associated with malignancy. METHODS: Fine-needle aspiration samples classified in
      1 of 3 indeterminate cytology categories were prospectively tested for N-, H-,
      and K-RAS mutations using next-generation sequencing assay. RESULTS: In the
      study, 93 patients with 94 nodules had preoperative RAS detected, of whom 86
      patients had an operation (69% total thyroidectomy, 29% lobectomy). In total, 76%
      of RAS-positive nodules were malignant and follicular variant papillary thyroid
      cancer was the most common cancer type (83%). HRAS mutations had the greatest
      risk of cancer (92%) followed by NRAS (74%) and KRAS (64%; P = .05). No
      preoperative variables were associated with malignancy including age (P = .07),
      sex (P = .49), RAS isoform (P = .05), mutational allelic frequency (P = .49),
      nodule size (P = .14), cytology category (P = .63), or ultrasound bilaterality (P
      = .24), multifocality (P = .23), or presence of >=1 suspicious feature (P = .86).
      Only 60% of patients with a unifocal nodule on ultrasound had single focus low
      risk encapsulated follicular variant papillary thyroid cancer or benign disease.
      CONCLUSION: Preoperative RAS mutation detection in thyroid nodules carries a
      substantial risk of cancer with a greater risk associated with HRAS and NRAS.
      Most RAS malignancies are follicular variant papillary thyroid cancer, which may
      inform the extent of operation.

PMID- 27863787
TI  - Characterizing the operative findings and utility of intraoperative parathyroid
      hormone (IOPTH) monitoring in patients with normal baseline IOPTH and
      normohormonal primary hyperparathyroidism.
AB  - BACKGROUND: During parathyroidectomy with intraoperative parathyroid hormone
      monitoring, the successful removal of a hypersecreting gland(s) resulting in
      normocalcemia is indicated by a >50% decrease in intraoperative parathyroid
      hormone level, typically into the normal range. Some patients, however, will have
      baseline parathyroid hormone levels within the normal range. We sought to
      determine the utility of intraoperative parathyroid hormone testing in these
      patients. METHODS: We retrospectively studied all patients who underwent
      parathyroidectomy for primary hyperparathyroidism at our institution over a 10
      year period. RESULTS: Overall, 317 (17%) patients had parathyroid hormone within
      the normal range at the onset of operation (baseline intraoperative parathyroid
      hormone), and 1,544 (83%) had classic primary hyperparathyroidism. The
      intraoperative parathyroid hormone degradation was slower in normal baseline
      intraoperative parathyroid hormone patients than classic primary
      hyperparathyroidism patients, though this did not reach statistical significance
      (P < .254). A >50% intraoperative parathyroid hormone decrease predicted cure in
      98.7% of normal baseline patients and 98.8% of classic primary
      hyperparathyroidism patients (P = .810). Normal baseline patients had a lesser
      cure rate the longer it took to achieve a 50% decrease intraoperatively; however,
      the cure rate was constant at any time point the 50% decrease occurred in
      patients with classic primary hyperparathyroidism (P < .05). CONCLUSION: The 50%
      rule delineating operative cure can be applied with equal confidence to patients
      with normal range, baseline intraoperative parathyroid hormone. Moreover, the
      time at which the 50% drop is achieved impacts operative success rates in these
      patients.

PMID- 27863788
TI  - Editorial: Treatment decision making in the era of genetic testing and molecular
      diagnostics.

PMID- 27863790
TI  - The history of the American Association of Endocrine Surgeons' Oliver Cope
      Meritorious Achievement Award and its eighth recipient: Stuart D. Wilson.

PMID- 27863791
TI  - Discussion.

PMID- 27863789
TI  - Comparative analysis of radioactive iodine versus thyroidectomy for definitive
      treatment of Graves disease.
AB  - BACKGROUND: Management of Graves disease includes antithyroid drugs, 131I
      therapy, or thyroidectomy. Our aim was to review our institutional experience
      with definitive treatments for Graves disease. METHODS: This was a retrospective
      review of patients undergoing 131I therapy (n = 295) or thyroidectomy (n = 103)
      for Graves disease (2003-2015). Demographic, clinical, pathology, and outcome
      data were collected from institutional databases. RESULTS: 131I therapy patients
      were older (39.1 years vs 33.4 years, P = .001). There was no difference in the
      presence of ophthalmopathy between groups. A larger proportion of children
      received thyroidectomy than 131I therapy (17.1% vs 9.2%, P = .026). The success
      rate of the first 131I therapy dose was 81.4%. Overall success rate, including
      additional doses, was 90.1%. Rapid turnover of iodine correlated with 131I
      therapy failure (58.3% rapid turnover failure vs 14.9% non-rapid turnover
      failure, P < .05). All surgical patients underwent total or near-total
      thyroidectomy. 131I therapy complications included worsening thyrotoxicosis (1%)
      and deteriorating orbitopathy (0.7%). Operative complications were higher than
      131I therapy complications (P < .05) but were transient. There was no worsening
      orbitopathy or recurrent Graves disease among surgical patients. CONCLUSION: A
      higher proportion of pediatric Graves disease patients underwent thyroidectomy
      than 131I therapy. Rapid turnover suggested more effective initial management
      with operation than 131I therapy. Although transient operative complications were
      high, 131I therapy complications included worsening of Graves orbitopathy among
      those with pre-existing orbitopathy.

PMID- 27863792
TI  - Presence of Latent Myofascial Trigger Points and Determination of Pressure Pain
      Thresholds of the Shoulder Girdle in Healthy Children and Young Adults: A Cross
      sectional Study.
AB  - OBJECTIVE: The primary objective of this study was to compare the number of
      myofascial trigger points (MTPs) and the pressure pain thresholds (PPTs) in the
      shoulder girdle, on the dominant and nondominant sides, between healthy children
      and adults. The secondary aim was to assess the correlations between the number
      of MTPs and the PPTs in these populations. METHODS: A cross-sectional study was
      performed. Thirty-five children (aged 9.1 +/- 1.7 years) and 35 adults (aged 23.4
      +/- 3.4 years) with no history of shoulder or cervical pathology were included.
      All participants were examined for MTPs in the shoulder muscles and assessed for
      PPTs in the neck, shoulder, and tibialis anterior. Parametric and nonparametric
      tests, effect sizes, and odds ratios were used to determine the differences
      between groups and sides. Spearman's sigma test was used to assess correlations
      between latent MTPs (LTPs) and PPTs in each group. RESULTS: Children had fewer
      LTPs than adults did (P = .03). The upper trapezius was the muscle with the
      largest number of LTPs, affecting 13 adults on the dominant side. Children had
      lower PPTs compared with adults (P < .05). Correlations between the number of
      LTPs (on both sides and in total) and PPTs were observed only in adults.
      CONCLUSIONS: Healthy children have fewer LTPs and lower PPTs in the shoulder
      girdle than healthy adults. A relationship was observed between sensitivity to
      pressure and the presence of LTPs in adults, in whom lower PPT was associated
      with more LTPs. This relationship was not detected in children.

PMID- 27863793
TI  - Plantar pressure asymmetry and risk of stress injuries in the foot of young
      soccer players.
AB  - BACKGROUND: Asymmetries in the magnitude of plantar pressure are considered a
      risk factor for stress fracture of the fifth metatarsal in soccer athletes.
      OBJECTIVE: To investigate the presence of plantar pressure asymmetries among
      young soccer athletes. DESIGN: Observational. SETTING: Laboratory. PARTICIPANTS:
      Thirty young adolescents divided into a soccer player group (n = 15) or a matched
      control group (n = 15). MAIN OUTCOME MEASURES: Mean plantar pressure was
      determined for seven different regions of the foot. Data were compared between
      the preferred and non-preferred foot, and between the groups, during barefoot
      standing on a pressure mat system. RESULTS: Higher pressure was found in the
      hallux, 5th metatarsal and medial rearfoot of the non-preferred foot in the young
      soccer players. These asymmetries were not observed in the control group.
      Magnitudes of plantar pressure did not differ between the groups. CONCLUSION:
      Young soccer players present asymmetries in plantar pressure in the hallux, 5th
      metatarsal and medial rearfoot, with higher pressure observed in the non
      preferred foot.

PMID- 27863794
TI  - Biotransfer of Cd along a soil-plant- mealybug-ladybird food chain: A comparison
      with host plants.
AB  - Agro-ecosystem contamination by the heavy metals present in different
      agricultural products is a serious challenge faced by the living organisms. This
      study explains the cadmium (Cd) transfer from soils contaminated with different
      cadmium concentrations through a plant (eggplant and tomato) - mealybug
      (Dysmicoccus neobrevipes) - predator (Cryptolaemus-montrouzieri) food chain. The
      soils were amended with Cd at the rates of 0, 12.5, 25 and 50 mg/kg (w/w). Our
      findings showed that considerably higher Cd transfer through tomato plant.
      Cadmium was biomagnified during soil-root transfer while bio-minimization of Cd
      was observed for shoot-mealybug - ladybird transfer. Our results further showed
      sequestration of Cd during the metamorphosis of ladybird beetle whilst transfer
      of Cd through soil-plant-mealybug-ladybird multi-trophic food chain increased in
      a dose dependent manner. Our results emphasize the need of further studies to
      elaborate possible mechanisms of Cd bio-minimization by plants, mealybugs and
      ladybirds observed during this study.

PMID- 27863795
TI  - Decomposition of acetaminophen in water by a gas phase dielectric barrier
      discharge plasma combined with TiO2-rGO nanocomposite: Mechanism and degradation
      pathway.
AB  - Acetaminophen (APAP) served as the model pollutant to evaluate the feasibility of
      pollutant removal by gas phase dielectric barrier discharge plasma combined with
      the titanium dioxide-reduced Graphene Oxide (TiO2-rGO) nanocomposite. TiO2-rGO
      nanocomposite was prepared using the modified hydrothermal method and
      characterized by TEM and XPS before and after plasma process. The results
      indicated that the APAP degradation efficiency was significantly improved to 92%
      after 18min of discharge plasma treatment coupling 0.25gL-1 TiO2-rGO 5%wt at
      18kV, compared with the plasma alone and plasma combined with P25 TiO2. The
      degradation mechanism for APAP in this system was studied by investigating the
      effects of the operational variables (e.g. discharge voltage and pH value) and
      the amount of the generated active species; and the results showed that O3 and
      H2O2 yields were influenced notably by adding TiO2-rGO. Also, it was observed
      that, compared with unused TiO2-rGO, the photocatalytic performance of used TiO2
      rGO declined after several recirculation times due to the further reduction of
      Graphene Oxide in plasma system. Finally, intermediate products were analyzed by
      UV-vis spectrometry and HPLC/MS, and possible transformation pathways were
      identified with the support of theoretically calculating the frontier electron
      density of APAP.

PMID- 27863796
TI  - Reprint of "Extracellular production of tellurium nanoparticles by the
      photosynthetic bacterium Rhodobacter capsulatus".
AB  - The toxic oxyanion tellurite (TeO32-) is acquired by cells of Rhodobacter
      capsulatus grown anaerobically in the light, via acetate permease ActP2 and then
      reduced to Te0 in the cytoplasm as needle-like black precipitates. Interestingly,
      photosynthetic cultures of R. capsulatus can also generate Te0 nanoprecipitates
      (TeNPs) outside the cells upon addition of the redox mediator lawsone (2-hydroxy
      1,4-naphtoquinone). TeNPs generation kinetics were monitored to define the
      optimal conditions to produce TeNPs as a function of various carbon sources and
      lawsone concentration. We report that growing cultures over a 10 days period with
      daily additions of 1mM tellurite led to the accumulation in the growth medium of
      TeNPs with dimensions from 200 up to 600-700nm in length as determined by atomic
      force microscopy (AFM). This result suggests that nucleation of TeNPs takes place
      over the entire cell growth period although the addition of new tellurium Te0 to
      pre-formed TeNPs is the main strategy used by R. capsulatus to generate TeNPs
      outside the cells. Finally, X-ray photoelectron spectroscopy (XPS) and Fourier
      transform infrared (FT-IR) analysis of TeNPs indicate they are coated with an
      organic material which keeps the particles in solution in aqueous solvents.

PMID- 27863797
TI  - Stabilization of Pb(II) accumulated in biomass through phosphate-pretreated
      pyrolysis at low temperatures.
AB  - The remediation of heavy metal-contaminated soil and water using plant biomass is
      considered to be a green technological approach, although the harmless disposal
      of biomass accumulated with heavy metals remains a challenge. A potential
      solution to this problem explored in this work involves combining phosphate
      pretreatment with pyrolysis. Pb(II) was accumulated in celery biomass with
      superior sorption capacity and also in ordinary wood biomass through biosorption.
      The Pb(II)-impregnated biomass was then pretreated with phosphoric acid or
      calcium dihydrogen phosphate (CaP) and pyrolyzed at 350 or 450 degrees C. Pb(II)
      from biomass was in turn almost totally retained in chars, and the percentage of
      DTPA-extractable Pb(II) was reduced to less than 5% of total Pb(II) in chars
      through CaP pretreatment. Pb(II) stabilization was further confirmed through a
      sequential extraction test, which showed that more than 95% of Pb(II) was
      converted into stable species composed mainly of lead phosphates according to X
      ray diffraction (XRD) and scanning electron microscopy/energy-dispersive X-ray
      spectroscopy (SEM/EDX) analyses. Overall, phosphate-pretreated pyrolysis can
      stabilize both Pb(II) and degradable biomass, so as to control efficiently the
      hazards of heavy metal-contaminated biomass.

PMID- 27863798
TI  - Use of soil amendments to immobilize antimony and lead in moderately contaminated
      shooting range soils.
AB  - Shooting ranges are a source of environmental concern around the world as they
      are a source of toxic antimony (Sb) and lead (Pb). In-situ chemical stabilization
      is a strategy to reduce metal(loid) leaching and bioavailability. However it is
      difficult to find the right treatment due to the fact that Pb is a cation and Sb
      an anion, under oxidised conditions and they often show the opposite mobility in
      soil, on the application of amendments. A batch experiment was set up with two
      soils (slightly acidic and alkaline), two red mud based amendments (ViroSoilTM 1
      and 2) alone and in combination with two reducing agents (zero valent iron and
      iron sulphate), to assess the effect of the treatments on metal(loid) leaching
      and compare it to unamended soil and soil amended with goethite, a known Sb
      adsorbent. Iron sulphate was effective at reducing Sb leaching due to the
      reduction of SbV to SbIII which bound more strongly to iron (hyr)oxides in soil.
      However it had an adverse effect on the leaching of Pb due to its acidifying
      effect and reductive dissolution of manganese (hyd)roxides. Combining ViroSoilTM
      amendments with FeSO4 still reduced Sb leaching but also Pb leaching and proved a
      suitable treatment.

PMID- 27863799
TI  - Retrospective analysis of the prevalence and incidence of caries in the distal
      surface of mandibular second molars in British military personnel.
AB  - Mandibular third molars are commonly removed because of distal caries in the
      adjacent tooth. To find out the prevalence of distal caries in mandibular second
      molars we retrospectively studied the primary care dental records of 720 British
      military personnel (653 men and 67 women) from various centres. These records are
      standardised and personnel are required to attend for inspection regularly. Those
      who had been under 20 years of age at enlistment, who had served for at least
      five years, and had five recorded dental inspections, were included. The median
      (IQR) period from the first to last inspection was 15 (9.7 - 19.2) years, and
      inspections were a median (IQR) of 14.1 (12.8 - 15.8) months apart. A total of
      59/1414 (4.2%) mandibular second molars developed caries in their distal
      surfaces. This was 4% higher when they were associated with a partially-erupted
      mandibular third molar than when associated with one that was fully erupted or
      absent (29/414 (7%) compared with 30/1000 (3%); p=0.001). Carious lesions
      developed in the distal aspect of 22/133 mandibular second molars (16.5%) that
      were adjacent to a mesioangularly impacted third molar. Of these, 19/22 were
      successfully restored. Four mesioangularly impacted mandibular third molars would
      have to be extracted to prevent one case of distal caries in a second molar
      (number needed to treat=3.25). Second molars that are associated with a partially
      erupted mesioangular mandibular third molar have a higher risk of caries, and
      this can be reduced by removal of the third molar. However, distal caries in
      second molars seems to be a treatable and slowly-developing phenomenon and we
      recommend that the merits and risks of the prophylactic removal of third molars
      should be discussed with the patient, who should have long-term clinical and
      radiographic checks if the tooth is retained.

PMID- 27863800
TI  - Rare incidence of two histologically different, separate tumours in the right
      parotid gland.

PMID- 27863801
TI  - Long-acting injectable antipsychotics for the prevention of relapse in patients
      with recent-onset psychotic disorders: A systematic review and meta-analysis of
      randomized controlled trials.
AB  - This meta-analysis of randomized controlled trials (RCTs) investigated the
      advantages of long-acting injectable antipsychotics (LAI-APs) over oral
      antipsychotics (OAPs) with regard to efficacy and safety for patients with recent
      onset psychotic disorders. Effect sizes and 95% confidence intervals (95%CIs)
      were calculated. We identified five RCTs (1022 patients, mean study duration=18+/
      7.59 months) that compared LAI-APs (paliperidone or risperidone) with OAPs.
      Pooled LAI-APs did not outperform OAPs in terms of the preventing of relapse
      (N=3, n=875). However, there was significant heterogeneity (I2=76%), with one
      study showing no superiority of LAI-APs over OAPs [Malla 2013: risk ratio
      (RR)=1.83, 95%CI=0.70-4.77, n=77] and the other two studies showing LAI-APs to be
      superior [Schreiner 2015: [RR=0.71, 95%CI=0.51-0.97, number needed to treat
      (NNT)=-17, n=715, Subotnik 2015: RR=0.15, 95%CI=0.04-0.63, NNT=-4, n=83]. Pooling
      the studies, there were no significant differences between LAI-APs and OAPs in
      the improvement of Positive and Negative Syndrome Scale scores or in
      discontinuation due to all-cause, adverse events (AEs), and death, but LAI-APs
      outperformed OAPs in terms of discontinuation due to inefficacy (RR=0.34, NNT=
      50) and nonadherence (RR=0.30, NNT=-33). However, the LAI-APs were associated
      with a higher incidence of at least one AE (RR=1.13) and tremor (RR=2.38)
      compared with OAPs.

PMID- 27863802
TI  - Calcium mass balance with citrate dialysate is lower than with acetate.

PMID- 27863804
TI  - Phthalate metabolites in 24-h urine samples of the German Environmental Specimen
      Bank (ESB) from 1988 to 2015 and a comparison with US NHANES data from 1999 to
      2012.
AB  - The German Environmental Specimen Bank (ESB) continuously collects 24-h urine
      samples since the early 1980s in Germany. In this study we analyzed 300 urine
      samples from the years 2007 to 2015 for 21 phthalate metabolites (representing
      exposure to 11 parent phthalates) and combined the data with two previous
      retrospective measurement campaigns (1988 to 2003 and 2002 to 2008). The combined
      dataset comprised 1162 24-h urine samples spanning the years 1988 to 2015. With
      this detailed set of human biomonitoring data we describe the time course of
      phthalate exposure in Germany over a time frame of 27 years. For the metabolites
      of the endocrine disrupting phthalates di(2-ethylhexyl) phthalate (DEHP), di-n
      butyl phthalate (DnBP) and butylbenzyl phthalate (BBzP) we observed a roughly ten
      fold decline in median metabolite levels from their peak levels in the late
      1980s/early 1990s compared to most recent levels from 2015. Probably, bans (first
      enacted in 1999) and classifications/labelings (enacted in 2001 and 2004) in the
      European Union lead to this drop. A decline in di-isobutyl phthalate (DiBP)
      metabolite levels set in only quite recently, possibly due to its later
      classification as a reproductive toxicant in the EU in 2009. In a considerable
      number of samples collected before 2002 health based guidance values (BE, HBM I)
      have been exceeded for DnBP (27.2%) and DEHP (2.3%) but also in recent samples
      some individual exceedances can still be observed (DEHP 1.0%). A decrease in
      concentration for all low molecular weight phthalates, labelled or not, was seen
      in the most recent years of sampling. For the high molecular weight phthalates,
      DEHP seems to have been substituted in part by di-isononyl phthalate (DiNP), but
      DiNP metabolite levels have also been declining in the last years. Probably, non
      phthalate alternatives increasingly take over for the phthalates in Germany. A
      comparison with NHANES (National Health and Nutrition Examination Survey) data
      from the United States covering the years 1999 to 2012 revealed both similarities
      and differences in phthalate exposure between Germany and the US. Exposure to
      critical phthalates has decreased in both countries with metabolite levels more
      and more aligning with each other, but high molecular weight phthalates
      substituting DEHP (such as DiNP) seem to become more important in the US than in
      Germany.

PMID- 27863803
TI  - Research domain criteria and the study of trauma in children: Implications for
      assessment and treatment research.
AB  - By definition, the Diagnostic and Statistical Manual (DSM) diagnosis of
      posttraumatic stress disorder (PTSD) requires exposure to a traumatic event. Yet,
      the DSM diagnostic requirements for children and adolescents for PTSD may fail to
      capture traumatized youth with significant distress and functional impairment.
      Many important studies have utilized PTSD diagnosis as a mechanism for grouping
      individuals for comparative studies examining brain functioning,
      neuroendocrinology, genetics, attachment, and cognition; however, focusing only
      on those with the diagnosis of PTSD can miss the spectrum of symptoms and
      difficulties that impact children who experience trauma and subsequent
      impairment. Some studying child trauma have focused on examining brain and
      biology of those with exposure and potential impairment rather than only those
      with PTSD. This line of inquiry, complementary to PTSD specific studies, has
      aided our understanding of some of the changes in brain structure and
      neuroregulatory systems at different developmental periods following traumatic
      exposure. Application of the Research Domain Criteria (RDoC) framework proposed
      by NIMH to the study of child trauma exposure and subsequent impairment is an
      opportunity to examine domains of function and how they are impacted by trauma.
      Research to date has focused largely in the areas of negative valence,
      regulatory, and cognitive systems, however those studying complex or
      developmental trauma have identified an array of domains that are impacted which
      map onto many of the RDoC categories. This paper will review the relevant
      literature associated with child trauma as it relates to the RDoC domains,
      outline areas of needed research, and describe their implications for treatment
      and the advancement of the field.

PMID- 27863805
TI  - Computational Dehydration of Crystalline Hydrates Using Molecular Dynamics
      Simulations.
AB  - Molecular dynamics (MD) simulations have evolved to an increasingly reliable and
      accessible technique and are today implemented in many areas of biomedical
      sciences. We present a generally applicable method to study dehydration of
      hydrates based on MD simulations and apply this approach to the dehydration of
      ampicillin trihydrate. The crystallographic unit cell of the trihydrate is used
      to construct the simulation cell containing 216 ampicillin and 648 water
      molecules. This system is dehydrated by removing water molecules during a 2200 ps
      simulation, and depending on the computational dehydration rate, different
      dehydrated structures were observed. Removing all water molecules immediately and
      removing water relatively fast (10 water molecules/10 ps) resulted in an
      amorphous system, whereas relatively slow computational dehydration (3 water
      molecules/10 ps) resulted in a crystalline anhydrate. The structural changes
      could be followed in real time, and in addition, an intermediate amorphous phase
      was identified. The computationally identified dehydrated structure (anhydrate)
      was slightly different from the experimentally known anhydrate structure
      suggesting that the simulated computational structure could represent a
      kinetically trapped dehydration intermediate.

PMID- 27863806
TI  - Pharmacokinetics, Safety, and Tolerability of Single and Multiple Doses of ABT
      493: A First-In-Human Study.
AB  - ABT-493 is a hepatitis C virus nonstructural protein 3/4A protease inhibitor with
      pangenotypic antiviral activity. This study investigated the pharmacokinetics,
      safety, and tolerability of single and multiple ascending doses of ABT-493 and
      the effect of food and ritonavir coadministration on ABT-493 pharmacokinetics in
      healthy adults. In the blinded, randomized, placebo-controlled phase 1 single-
      and multiple-dose portions of the study, ABT-493 25-800 mg were evaluated as
      single doses, and 200, 400, and 800 mg were evaluated as multiple doses. The
      effect of food and ritonavir was assessed in a crossover unblinded fashion. ABT
      493 pharmacokinetic parameters were estimated using noncompartmental methods. ABT
      493 25-800 mg showed a greater than dose-proportional increase in exposures.
      Minimal accumulation (<=15%) was observed after ABT-493 200- and 400-mg multiple
      dosing; higher accumulations (approximately 80%) were observed after the 800-mg
      dose. ABT-493 harmonic mean half-life was 6-9 hours. Food had a minimal effect on
      ABT-493 exposures. All adverse events were assessed by the investigator as mild
      to moderate in severity, no serious adverse events were reported, and no subjects
      discontinued from the study. No clinically significant laboratory tests, vital
      signs, or electrocardiogram values were reported. A maximum tolerated dose was
      not reached.

PMID- 27863807
TI  - Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid
      arthritis: 2-year efficacy and safety results from the randomised EXXELERATE
      study.
AB  - BACKGROUND: To date, head-to-head trials comparing the efficacy and safety of
      biological disease-modifying antirheumatic drugs within the same class, including
      TNF inhibitors, in patients with active rheumatoid arthritis despite methotrexate
      therapy are lacking. We aimed to compare the efficacy and safety of two different
      TNF inhibitors and to assess the efficacy and safety of switching to the other
      TNF inhibitor without a washout period after insufficient primary response to the
      first TNF inhibitor at week 12. METHODS: In this 104-week, randomised, single
      blind (double-blind until week 12 and investigator blind thereafter), parallel
      group, head-to-head superiority study (EXXELERATE), eligible patients from 151
      centres worldwide were aged 18 years or older with a diagnosis of rheumatoid
      arthritis at screening, as defined by the 2010 ACR/EULAR criteria, and had
      prognostic factors for severe disease progression, including a positive
      rheumatoid factor, or anti-cyclic citrullinated peptide antibody result, or both.
      Participants were randomly assigned (1:1) via an interactive voice and web
      response system with no stratification to receive certolizumab pegol plus
      methotrexate or adalimumab plus methotrexate. All study staff were kept masked
      throughout the study and participants were masked until week 12. At week 12,
      patients were classified as responders (by either achieving low disease activity
      [LDA] according to Disease Activity Score 28-erythrocyte sedimentation rate
      [DAS28-ESR] <=3.2 or DAS28-ESR reduction >=1.2 from baseline) or as non
      responders. Non-responders to the first TNF inhibitor to which they were
      randomised were switched to the other TNF inhibitor with no washout period.
      Primary endpoints were the percentage of patients achieving a 20% improvement
      according to the American College of Rheumatology criteria (ACR20) at week 12 and
      LDA at week 104 (week 12 non-responders were considered LDA non-responders). This
      study is registered with ClinicalTrials.gov, number NCT01500278. FINDINGS:
      Between Dec 14, 2011, and Nov 11, 2013, 1488 patients were screened of whom 915
      were randomly assigned; 457 to certolizumab pegol plus methotrexate and 458 to
      adalimumab plus methotrexate. No statistically significant difference was
      observed in ACR20 response at week 12 (314 [69%] of 454 patients and 324 [71%] of
      454 patients; odds ratio [OR] 0.90 [95% CI 0.67-1.20]; p=0.467) or DAS28-ESR LDA
      at week 104 (161 [35%] of 454 patients and 152 [33%] of 454 patients; OR 1.09
      [0.82-1.45]; p=0.532) between certolizumab pegol plus methotrexate and adalimumab
      plus methotrexate, respectively. At week 12, 65 non-responders to certolizumab
      pegol were switched to adalimumab and 57 non-responders to adalimumab were
      switched to certolizumab pegol; 33 (58%) of 57 patients switching to certolizumab
      pegol and 40 (62%) of 65 patients switching to adalimumab responded 12 weeks
      later by achieving LDA or a DAS28-ESR reduction 1.2 or greater. 389 [75%] of 516
      patients who received certolizumab pegol plus methotrexate and 386 [74%] of 523
      patients who received adalimumab plus methotrexate reported treatment-emergent
      adverse events. Three deaths (1%) occurred in each group. No serious infection
      events were reported in the 70-day period after treatment switch. INTERPRETATION:
      These results show that certolizumab pegol plus methotrexate is not superior to
      adalimumab plus methotrexate. The data also show the clinical benefit and safety
      of switching to a second TNF inhibitor without a washout period after primary
      failure to a first TNF inhibitor. FUNDING: UCB Pharma.

PMID- 27863808
TI  - Targeting tau protein in Alzheimer's disease.

PMID- 27863810
TI  - Bending the blood pressure curve down: are we succeeding?

PMID- 27863811
TI  - EXXELERATE: a negative trial with importance for clinical practice.

PMID- 27863809
TI  - Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or
      moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel
      arm, phase 3 trial.
AB  - BACKGROUND: Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable
      reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau
      protein aggregation both in vitro and in transgenic mouse models.
      Methylthioninium chloride has previously shown potential efficacy as monotherapy
      in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe
      and effective in modifying disease progression in patients with mild to moderate
      Alzheimer's disease. METHODS: We did a 15-month, randomised, controlled double
      blind, parallel-group trial at 115 academic centres and private research clinics
      in 16 countries in Europe, North America, Asia, and Russia with patients younger
      than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly
      using other medicines for Alzheimer's disease were permitted to be included
      because we considered it infeasible not to allow their inclusion; however,
      patients using medicines carrying warnings of methaemoglobinaemia were excluded
      because the oxidised form of methylthioninium in high doses has been shown to
      induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM
      twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to
      maintain blinding with respect to urine or faecal discolouration) administered as
      oral tablets. We did the randomisation with an interactive web response system
      using 600 blocks of length ten, and stratified patients by severity of disease,
      global region, whether they were concomitantly using Alzheimer's disease-labelled
      medications, and site PET capability. Participants, their study partners
      (generally carers), and all assessors were masked to treatment assignment
      throughout the study. The coprimary outcomes were progression on the Alzheimer's
      Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer's
      Disease Co-operative Study-Activities of Daily Living Inventory (ADCS-ADL) scales
      from baseline assessed at week 65 in the modified intention-to-treat population.
      This trial is registered with Clinicaltrials.gov (NCT01689246) and the European
      Union Clinical Trials Registry (2012-002866-11). FINDINGS: Between Jan 29, 2013,
      and June 26, 2014, we recruited and randomly assigned 891 participants to
      treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM
      twice a day). The prespecified primary analyses did not show any treatment
      benefit at either of the doses tested for the coprimary outcomes (change in ADAS
      Cog score compared with control [n=354, 6.32, 95% CI 5.31-7.34]: 75 mg LMTM twice
      a day [n=257] -0.02, -1.60 to 1.56, p=0.9834, 125 mg LMTM twice a day [n=250] 
      0.43, -2.06 to 1.20, p=0.9323; change in ADCS-ADL score compared with control [
      8.22, 95% CI -9.63 to -6.82]: 75 mg LMTM twice a day -0.93, -3.12 to 1.26,
      p=0.8659; 125 mg LMTM twice a day -0.34, -2.61 to 1.93, p=0.9479).
      Gastrointestinal and urinary effects were the most common adverse events with
      both high doses of LMTM, and the most common causes for discontinuation. Non
      clinically significant dose-dependent reductions in haemoglobin concentrations
      were the most common laboratory abnormality. Amyloid-related imaging
      abnormalities were noted in less than 1% (8/885) of participants. INTERPRETATION:
      The primary analysis for this study was negative, and the results do not suggest
      benefit of LMTM as an add-on treatment for patients with mild to moderate
      Alzheimer's disease. Findings from a recently completed 18-month trial of
      patients with mild Alzheimer's disease will be reported soon. FUNDING: TauRx
      Therapeutics.

PMID- 27863812
TI  - Open letter on the SDGs: a robust measure for universal health coverage is
      essential.

PMID- 27863814
TI  - Erratum to "Personalized peptide vaccine-induced immune response associated with
      long-term survival of a metastatic cholangiocarcinoma patient".

PMID- 27863815
TI  - Risk factors for recurrent wheezing in the first year of life in the city of
      Cordoba, Argentina.
AB  - BACKGROUND: Wheezing is a very common respiratory symptom in infants. The
      prevalence of wheezing in infants, conducted in developed countries shows
      prevalence rates ranging between 20% and 30%. However, we do not know the risk
      factors in our population of wheezing infants. METHODS: A standardised written
      questionnaire (WQ-P1-EISL) in infants between 12 and 18 months of age residing in
      the city of Cordoba was used; population/sample included 1031 infants. Recurrent
      wheezing (RW) was defined as three or more episodes of wheezing reported by the
      parents during the first 12 months of life. Data obtained were coded in Epi
      InfoTM (version 7) and statistically analysed with SPSS (version 17.5) software
      in Spanish. Parametric tests (one-way ANOVA) were performed for identifying
      significantly associated variables. RESULTS: The prevalence of wheezing infants
      was 39.7%; recurrent wheezing 33%; and severe wheezing 14.7%; 13.7% had pneumonia
      before the first year and of these 6.3% were hospitalised, multiple variables as
      risk factors for wheezing were found such as: >6 high airway infections and
      bronchiolitis in the first three months of life, smokers who smoke in the home
      among other risk factors and protective factors in those who have an elevated
      socioeconomic status. CONCLUSION: It is known that persistent respiratory
      problems in children due to low socioeconomic status is a risk factor for
      wheezing, pneumonia and could be a determining factor in the prevalence and
      severity of RW in infants. Research suggests that there are areas for improvement
      in the implementation of new educational strategies.

PMID- 27863816
TI  - Incidence of allergic rhinitis in a cohort of young adults from 13-15 years old
      to 23-25 years old in Castellon (Spain).
AB  - BACKGROUND: The objective of this study was to estimate the incidence of Allergic
      Rhinitis (AR) in young adults and its risk or protective factors. METHODS: A
      population-based prospective cohort study was carried out in 2012. The cohort
      participated in the International Study of Asthma and Allergy in Childhood in
      Castellon in 1994 and 2002. A telephone survey was conducted using the same
      questionnaires. A new case of AR was defined as the participants free of the
      disease in 2002, who self-reported suffering from AR or taking medications for AR
      in the period 2002-2012. RESULTS: Of the 1805 schoolchildren in the cohort in
      2002, 1435 young adults (23-25 years old) participated (follow-up 79.1%) in 2012;
      743 were female and 692 male; their mean age was 24.9+/-0.6 years. Two hundred
      new cases of AR occurred in 1259 participants free of the disease with an
      incidence of 17.3 per 1000 person-years, and the incidence increased from 2002
      (RR=1.42; 95% CI 1.15-1.75). The risk factors of AR adjusted by age and gender
      were sinusitis (RR=1.77; 95% CI 1.16-2.68), atopic dermatitis (RR=1.51; 95% CI
      1.11-2.06) and constant exposure to truck traffic (RR=1.88; 95% CI 1.12-3.17).
      For male participants, the risk factors were asthma, sinusitis and atopic
      dermatitis, and for females bronchitis was a risk factor and presence of older
      siblings a protective factor. CONCLUSIONS: An increase in AR incidence was
      observed. Sinusitis, atopic dermatitis and constant exposure to truck traffic
      were the risk factors of the AR with some differences by gender.

PMID- 27863817
TI  - Tumor clone dynamics in lethal prostate cancer.

PMID- 27863818
TI  - Re: Ten-year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized
      Prostate Cancer.

PMID- 27863819
TI  - Unfounded concerns about the use of automated office blood pressure measurement
      in SPRINT.
AB  - SPRINT reported significantly fewer cardiovascular events when patients with a
      higher cardiovascular risk were treated to a target systolic blood pressure (BP)
      of <120 versus <140 mm Hg. In SPRINT, BP was recorded using the automated office
      BP (AOBP) method, with multiple readings being taken automatically with the
      patient resting alone. This technique for BP measurement eliminates the white
      coat effect and gives lower BP readings than conventional manual office BP.
      Critics have questioned if the readings were actually taken with the subject
      alone and have expressed concerns about the time taken to obtain the readings and
      the cost of automated sphygmomanometers. Others have suggested that the findings
      in SPRINT can be applied to current clinical practice if a correction factor is
      used to convert conventional BP readings to AOBP. This article responds to these
      criticisms and explains why current methods for recording BP in clinical practice
      should be changed to AOBP, the technique for BP measurement used in SPRINT.

PMID- 27863820
TI  - B cell depleting therapy regulates splenic and circulating T follicular helper
      cells in immune thrombocytopenia.
AB  - B cells are involved in immune thrombocytopenia (ITP) pathophysiology by
      producing antiplatelet auto-antibodies. However more than a half of ITP patients
      do not respond to B cell depletion induced by rituximab (RTX). The persistence of
      splenic T follicular helper cells (TFH) that we demonstrated to be expanded
      during ITP and to support B cell differentiation and antiplatelet antibody
      production may participate to RTX inefficiency. Whereas it is well established
      that the survival of TFH depends on B cells in animal models, nothing is known in
      humans yet. To determine the effect of B cell depletion on human TFH, we
      quantified B cells and TFH in the spleen and in the blood from ITP patients
      treated or not with RTX. We showed that B cell depletion led to a dramatic
      decrease in splenic TFH and in CXCL13 and IL-21, two cytokines predominantly
      produced by TFH. The absolute count of circulating TFH and serum CXCL13 also
      decreased after RTX treatment, whatever the therapeutic response. Therefore, we
      showed that the maintenance of TFH required B cells and that TFH are not involved
      in the inefficiency of RTX in ITP.

PMID- 27863821
TI  - Analyzing recurrent events when the history of previous episodes is unknown or
      not taken into account: proceed with caution.
AB  - OBJECTIVE: Researchers in public health are often interested in examining the
      effect of several exposures on the incidence of a recurrent event. The aim of the
      present study is to assess how well the common-baseline hazard models perform to
      estimate the effect of multiple exposures on the hazard of presenting an episode
      of a recurrent event, in presence of event dependence and when the history of
      prior-episodes is unknown or is not taken into account. METHODS: Through a
      comprehensive simulation study, using specific-baseline hazard models as the
      reference, we evaluate the performance of common-baseline hazard models by means
      of several criteria: bias, mean squared error, coverage, confidence intervals
      mean length and compliance with the assumption of proportional hazards. RESULTS:
      Results indicate that the bias worsen as event dependence increases, leading to a
      considerable overestimation of the exposure effect; coverage levels and
      compliance with the proportional hazards assumption are low or extremely low,
      worsening with increasing event dependence, effects to be estimated, and sample
      sizes. CONCLUSIONS: Common-baseline hazard models cannot be recommended when we
      analyse recurrent events in the presence of event dependence. It is important to
      have access to the history of prior-episodes per subject, it can permit to obtain
      better estimations of the effects of the exposures.

PMID- 27863822
TI  - Surgical site infection reporting: more than meets the agar.
AB  - BACKGROUND/PURPOSE: Surgical site infection (SSI) rate in pediatric appendicitis
      is a commonly used hospital quality metric. We hypothesized that surveillance of
      organ-space SSI (OSI) using cultures alone would fail to capture many clinically
      important events. METHODS: A prospective, multidisciplinary surveillance program
      recorded 30-day SSI and hospital length of stay (LOS) for patients <18years
      undergoing appendectomy for perforated appendicitis from 2012 to 2015.
      Standardized treatment pathways were utilized, and OSI was identified by imaging
      and/or bacterial cultures. RESULTS: Four hundred ten appendectomies for
      perforated appendicitis were performed, and a total of 84 OSIs (20.5%) were
      diagnosed with imaging. Positive cultures were obtained for 39 (46%) OSIs,
      whereas 45 (54%) had imaging only. Compared to the mean LOS for patients without
      OSI (5.2+/-2.9days), LOS for patients with OSI and positive cultures (13.7+/
      5.4days) or with OSI without cultures (10.4+/-3.7days) was significantly longer
      (both p<0.001). The OSI rate identified by positive cultures alone was 9.5%,
      whereas the clinically-relevant OSI rate was 20.5%. CONCLUSIONS: Using positive
      cultures alone to capture OSI would have identified less than half of clinically
      important infections. Utilizing clinically-relevant SSI is an appropriate metric
      for comparing hospital quality but requires agreed upon standards for diagnosis
      and reporting. LEVEL OF EVIDENCE: II. TYPE OF STUDY: Diagnostic study.

PMID- 27863823
TI  - General endotracheal vs. non-endotracheal regional anesthesia for elective
      inguinal hernia surgery in very preterm neonates: A single institution
      experience.
AB  - BACKGROUND: Very pre-term infants (VP) at <32 weeks post menstrual age PMA have a
      high incidence of bronchopulmonary dysplasia BPD. BPD places them at risk for
      pulmonary-related perioperative complications from general endotracheal
      anesthesia GE during elective inguinal hernia repair. METHODS: A retrospective
      cohort study was done to compare pulmonary-related perioperative risks between VP
      patients undergoing non-emergent inguinal hernia repair prior to NICU discharge
      under GE (n=58) vs regional anesthesia RA (n=37). RESULTS: Median PMA (RA 26 vs
      GE 27 weeks), operative weight (RA 2.2 vs GE 2.27 kg), % with BPD, medical and
      surgical comorbidities, number of concurrent procedures are similar between
      groups, except for sac laparoscopy (0% RA vs 36% GE). Procedural anesthesia time
      was 40 minutes for RA vs 69 minutes for GE, (p < 0.001). GE (17%) vs RA (0%)
      remained intubated post op (p<0.001). Oral feeding was fully tolerated in RA
      (97%) vs GE (72%, p=0.002) by 48h after surgery. The statistical differences hold
      after regression analysis controlling for sac laparoscopy and procedure time. No
      difference in intraoperative or postoperative hernia complications is found.
      CONCLUSION: RA is safe. RA is associated with early resumption of full feed,
      avoidance of prolonged mechanical intubation. We recommend a randomized
      controlled trial comparing the safety and efficacy of GE vs RA in VP infants
      undergoing elective NICU inguinal hernia repair. LEVEL OF EVIDENCE: II
      Retrospective study.

PMID- 27863824
TI  - The financial impact of flipping the coin.
AB  - BACKGROUND: Esophageal foreign body retrieval is typically performed by rigid or
      flexible esophagoscopy. Despite evidence supporting the efficacy and safety of
      balloon extraction, it is rarely performed. We sought to establish the financial
      benefits of this minimally invasive approach. METHODS: A retrospective review of
      241 children with esophageal coins between 2011 and 2013 was performed. Coins
      were removed via endoscopy or fluoroscopic-guided balloon retrieval. Timing,
      symptoms, facility cost, and patient charges were compared. RESULTS: Two hundred
      patients had attempted balloon retrieval with 80% success. Forty-one patients
      went directly for operative removal. Patients with respiratory difficulty
      (p=0.05), wheezing (p<0.01), or fever (p=0.03) were more often taken directly for
      endoscopic retrieval. The median cost and charges for attempted balloon
      extraction were $484 and $1647. The median cost and charges for primary endoscopy
      were $1834 and $6746. The median total cost and charges of attempted balloon
      extraction including ED, OR, transport, admission, and balloon retrieval were
      $1231 and $3539 versus $3615 and $12,204 in the primary endoscopy group (p<0.001,
      p<0.001). Seventeen percent of patients who underwent attempted balloon retrieval
      were admitted prior to removal compared to 76% who underwent primary endoscopy
      (p<0.001). CONCLUSIONS: Fluoroscopic guided balloon extraction of esophageal
      coins is a financially prudent choice which shortens hospital stay. LEVEL OF
      EVIDENCE: III. TYPE OF STUDY: Retrospective treatment and economic study.

PMID- 27863825
TI  - Implications of lipid monolayer charge characteristics on their selective
      interactions with a short antimicrobial peptide.
AB  - Many antimicrobial peptides (AMPs) target bacterial membranes and they kill
      bacteria by causing structural disruptions. One of the fundamental issues however
      lies in the selective responses of AMPs to different cell membranes as a lack of
      selectivity can elicit toxic side effects to mammalian host cells. A key
      difference between the outer surfaces of bacterial and mammalian cells is the
      charge characteristics. We report a careful study of the binding of one of the
      representative AMPs, with the general sequence G(IIKK)4I-NH2 (G4), to the spread
      lipid monolayers of DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) and DPPG
      (1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt)) mimicking
      the charge difference between them, using the combined measurements from Langmuir
      trough, Brewster angle microscopy (BAM) and neutron reflection (NR). The
      difference in pressure rise upon peptide addition into the subphase clearly
      demonstrated the different interactions arising from different lipid charge
      features. Morphological changes from the BAM imaging confirmed the association of
      the peptide into the lipid monolayers, but there was little difference between
      them. However, NR studies revealed that the peptide bound 4 times more onto the
      DPPG monolayer than onto the DPPC monolayer. Importantly, whilst the peptide
      could only be associated with the head groups of DPPC it was well penetrated into
      the entire DPPG monolayer, showing that the electrostatic interaction
      strengthened the hydrophobic interaction and that the combined molecular
      interactive processes increased the power of G4 in disrupting the charged
      membranes. The results are discussed in the context of general antibacterial
      actions as observed from other AMPs and membrane lytic actions.

PMID- 27863826
TI  - [An unusual cause of acute respiratory failure].

PMID- 27863827
TI  - [Assessment of physicians' and nurses' knowledge and practices of aerosol
      therapy].
AB  - INTRODUCTION: Aerosol therapy is an efficient, but complex procedure. National
      and international practice guidelines are regularly updated. However, only a few
      studies have assessed the application of guidelines by users. The aim of this
      study is to assess the knowledge and practices of physicians and nurses regarding
      these guidelines. METHODS: Two self-administered questionnaires were designed by
      a working team and presented to physicians and nurses of four university
      hospitals in Paris. A pharmacy resident collected and analyzed the data with the
      aid of an online survey website. RESULTS: A total of 481 physicians and nurses
      completed the questionnaires (33 % of physicians and 67 % of nurses). Only
      241/480 physicians and nurses (50 %) knew that several intravenous drugs cannot
      be nebulized. Ninety-four of 422 (22 %) of them always choose oxygen as the
      driving gas and 239/311 nurses (77 %) think that single use nebulizers can be re
      used for the same patient. CONCLUSIONS: This survey shows that many physicians
      and nurses lack knowledge and use inappropriate practices. Based on these
      results, a booklet has been designed by the working team. This booklet should
      help health professionals to harmonize practices across hospitals and to follow
      the guidelines correctly.

PMID- 27863829
TI  - The Effect of Carpal Tunnel Release on Typing Performance.
AB  - PURPOSE: To describe the effect of carpal tunnel release (CTR) on typing
      performance. METHODS: We prospectively studied 27 patients undergoing open CTR.
      Patient demographics and clinical characteristics including nerve conduction
      studies, electromyography results, and duration of symptoms were collected.
      Before surgery and at 8 time points after surgery, ranging from 1 to 12 weeks,
      typing performance for an approximately 500-character paragraph was assessed via
      an on-line platform. The Michigan Hand Questionnaire (MHQ) and the Boston Carpal
      Tunnel Questionnaire functional component (BCTQ-F) and symptom severity component
      (BCTQ-S) component were completed before surgery and at 1, 3, 6, and 12 weeks
      after surgery. We used repeated-measures analyses of variance and follow-up
      dependent-samples t tests to analyze change in typing performance across
      sessions, and linear regressions to assess relationships between typing
      performance and demographic and outcome measures. We compared typing speed with
      the MHQ, BCTQ-F, and BCTQ-S using the Pearson correlation test. RESULTS: Average
      typing speed decreased significantly from 49.7 +/- 2.7 words per minute (wpm)
      before surgery to 45.2 +/- 3.1 wpm at 8 to 10 days after surgery. Mean typing
      speed for the group exceeded the preoperative value between weeks 2 and 3, with
      continued improvement to 53.5 +/- 3.5 wpm at 12 weeks after surgery. No clinical
      or demographic variables were associated with the rate of recovery or the
      magnitude of improvement after CTR. The MHQ, BCTQ-F, and BCTQ-S each demonstrated
      significant improvement from preoperative values over the 12-week period. The MHQ
      and BCTQ-F scores correlated well with typing speed. CONCLUSIONS: On average,
      typing speed returned to preoperative levels between 2 and 3 weeks after CTR and
      typing speed showed improvement beyond preoperative levels after surgery. The MHQ
      and BCTQ-F correlate well with typing speed after CTR. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Prognostic IV.

PMID- 27863828
TI  - [Health care providers' knowledge and abilities to use inhalation devices and
      spacers].
AB  - INTRODUCTION: Inhaled therapy is the mainstay of asthma treatment due to its
      local and rapid action. However, its efficiency relies on the teaching of a good
      inhalation technique by health care providers. We assessed health care providers'
      knowledge and practical skills in the use of inhalation devices. METHODS: An
      observational multicenter study was conducted in the pulmonology and paediatric
      wards in Marseille. The departments' common practices, theoretical knowledge and
      practical skills were assessed through a questionnaire and a demonstration using
      a spacer device. RESULTS: Forty health care providers were interviewed (9
      attending physicians, 14 residents, 16 nurses and 1 physiotherapist), in 8
      different pulmonology and paediatric wards. A total of 42.5% reported previous
      training in inhalation device technique. When evaluating theoretical knowledge,
      we found a mean of 54% correct answers. Attending physicians did significantly
      better than residents and nurses. With regard to practical skills, we found a
      mean of 1.12 failed steps out of 7. Here again attending physicians did
      significantly better than residents and nurses. CONCLUSION: Based on the results
      of our study, we recommend that attending physicians provide training of
      inhalation technique to nurses and residents, as they did significantly better
      theoretically and practically.

PMID- 27863830
TI  - Caveolin-3 is aberrantly expressed in skeletal muscle cells in myasthenia gravis.
AB  - Caveolin-3 is a muscle-specific membrane protein that localizes to the sarcolemma
      and T-tubule system. Caveolin-3 is needed for muscle repair and skeletal muscle
      development. The objective of this study was to compare caveolin-3 expression in
      myasthenia gravis (MG) and control muscles. Caveolin-3 was abnormally expressed
      in the MG muscle membrane, with partial loss of expression and overexpression in
      5/15 and 10/15 patients, respectively. Caveolin-3 mRNA and protein levels were
      higher in MG than in control muscles, suggesting that partial deficiency of
      caveolin-3 is occasionally detected in MG muscle and that caveolin-3
      overexpression may be required after MG muscle damage.

PMID- 27863832
TI  - Management of non-ST-elevation myocardial infarction: A constant challenge.

PMID- 27863831
TI  - Therapy of Treatment-Related Hypertension in Metastatic Renal-Cell Cancer
      Patients Receiving Sunitinib.
AB  - INTRODUCTION: Treatment-related hypertension (tHTN) is frequent during sunitinib
      treatment. However, data on risk factors and treatment of tHTN remain scarce.
      PATIENTS AND METHODS: Patients with metastatic renal-cell carcinoma treated with
      sunitinib from June 2004 to December 2011 were included. Medical records were
      retrospectively analyzed for tHTN risk factors and antihypertensive treatments
      (AHT). Descriptive statistics, Cox regression, and competitive risk models were
      applied. RESULTS: A total of 51 (70.8%) of 72 patients developed tHTN after a
      median sunitinib treatment of 28 days. Mean blood pressure increased from 130/75
      (range, 90 to 190/58 to 101) mm Hg on day 1 to 140/80 (range, 90 to 190/60 to
      120, P < .001) mm Hg on day 28. Standard dose of sunitinib, age > 50 years, and
      prehypertension were identified as independent risk factors for tHTN. Thirty
      eight patients (72.5%) in the tHTN subgroup received modification of AHT. Calcium
      channel blockers (CCB) were identified as the best at controlling tHTN compared
      to other drugs (P = .045). The combination of AHT was more potent than a dose
      increase of a single-drug AHT, and early AHT intervention was more efficacious
      than delayed start of therapy. CONCLUSION: Patients at risk for tHTN require more
      rigorous blood pressure measurement. CCB seemed to be most potent and efficient,
      and an early combination of different classes of AHT was more efficacious than
      full-dose, single-agent AHT.

PMID- 27863833
TI  - Rapid Systematic Review: Intra-Arterial Thrombectomy ("Clot Retrieval") for
      Selected Patients with Acute Ischemic Stroke.
AB  - BACKGROUND: Acute ischemic stroke (AIS) is a leading cause of morbidity and
      mortality. However, precisely defining the optimal treatment for individual
      patients early after AIS onset remains elusive. There has recently been a surge
      in published studies documenting the effectiveness of mechanical intra-arterial
      thrombectomy for treatment of a subset of patients with AIS. This therapy has
      been proposed and studied for the small (<1.2%) subgroup of patients with
      ischemic strokes who have "large vessel" strokes or strokes that fail to improve
      after the administration of tissue plasminogen activator (t-PA). The current
      rapid systematic review provides practicing emergency physicians updated
      information regarding mechanical thrombectomy as a treatment option for carefully
      selected AIS patients. METHODS: A PubMed literature search was conducted from
      January 1996 to June 2016 and limited to human clinical trials written in English
      with relevant keywords. High-quality randomized controlled studies identified
      then underwent a structured review. RESULTS: In total, 179 papers fulfilling the
      search criteria were screened and 8 appropriate articles were rigorously reviewed
      in detail and recommendations given on the effectiveness and indication of
      mechanical intra-arterial thrombectomy for the treatment of AIS. CONCLUSIONS:
      Mechanical intra-arterial thrombectomy reduces long-term disability in a properly
      selected subset of patients who have an AIS caused by large vessel occlusion.
      Many of these patients will have failed to improve after intravenous
      administration of t-PA, and mortality is not increased when combined with t-PA.
      Careful screening criteria should be in place to identify the limited subset of
      patients to whom this therapy is delivered to derive optimal treatment benefits.

PMID- 27863834
TI  - Correlation Between United States Medical Licensing Examination and Comprehensive
      Osteopathic Medical Licensing Examination Scores for Applicants to a Dually
      Approved Emergency Medicine Residency.
AB  - BACKGROUND: It is important for emergency medicine (EM) residency programs to be
      able to correlate the United States (US) Medical Licensing Examination (USMLE)
      and Comprehensive Osteopathic Medical Licensing Examination (COMLEX) scores of
      applicants. OBJECTIVE: We sought to determine the correlation between USMLE and
      COMLEX scores for EM residency applicants. METHODS: Retrospectively, from 2006
      through 2013, USMLE and COMLEX examination scores for applicants to our 4-year,
      56-member, dually approved EM residency were analyzed. Using the COMLEX score as
      the outcome variable and USMLE score as the predictor, multiple linear regression
      models, stratified by test step, were created. RESULTS: There were 556 students
      representing 25 discrete medical schools included. Pair 1 consisted of applicants
      submitting COMLEX Level-1 and USMLE Step-1 scores (n = 486). Pair 2 were those
      with COMLEX Level-2 and USMLE Step-2 scores (n = 356). For Pair 1, mean, standard
      deviation, and median scores on the COMLEX were 551, 69, and 548, respectively;
      for the USMLE, scores were 216, 16, and 217, respectively. Results for Pair 2 on
      COMLEX were 566, 80, and 562, respectively; USMLE results were 228, 18, and 229,
      respectively. A strong correlation was observed for Pair 1 (r = 0.78; p < 0.001).
      A 1-point increase in USMLE Step-1 is associated with a 3.55-point increase in
      the COMLEX Level-1 score (beta = 3.55; 95% confidence interval [CI] 3.30-3.80; p
      < 0.001). A similar strong correlation was observed for Pair 2 (r = 0.72; p <
      0.001), where a 1-point increase in USMLE Step-2 is associated with a 3.29-point
      increase in the COMLEX Level-2 score (beta = 3.29; 95% CI 2.96-3.62; p < 0.001).
      CONCLUSIONS: A strong positive correlation between Steps 1 and 2 of the USMLE and
      COMLEX was found.

PMID- 27863835
TI  - Metabolites profiling reveals for antimicrobial compositional differences and
      action mechanism in the toothbrushing stick "miswak" Salvadora persica.
AB  - Among many plant species suitable for preparing toothbrushing sticks, miswak
      (Salvadora persica, family Salvadoraceae) is found the most effective tool for
      oral hygiene. S. persica possesses antibacterial, antiviral and antifungal
      effects against oral microbes, mostly due to its benzyl isothiocyanate content.
      To provide insight into S. persica chemical composition, volatile constituents
      from roots and stems of S. persica grown in Egypt and Saudi Arabia were profiled
      using solid-phase microextraction (SPME) coupled to gas chromatography-mass
      spectrometry (GC-MS). A total of 21 volatiles were identified with sulfur
      compounds amounting for the major volatile class. Orthogonal projection to latent
      structures-discriminant analysis (OPLS-DA) revealed for benzyl isothiocyanate
      (BITC) enrichment in roots versus stems. Primary metabolites contributing to S.
      persica taste viz. sugars and organic acids were profiled using GC-MS with
      silylation. Polyols (sugars) viz. arabitol, meso-erythritol, and mannitol were
      found to predominate sugars composition in S. persica stems being most enriched
      in meso-erythritol. The impact of saliva on S. persica aroma profile was further
      assessed and revealing for no enhancement in BITC production with salivation, and
      further not being detected in toothpaste preparation claimed to contain S.
      persica extract. This study provides the most complete profile of volatiles,
      sugars, and organic acids in S. persica organs and more rationalizing its use as
      a toothbrush.

PMID- 27863836
TI  - Looking at flubromazolam metabolism from four different angles: Metabolite
      profiling in human liver microsomes, human hepatocytes, mice and authentic human
      urine samples with liquid chromatography high-resolution mass spectrometry.
AB  - Flubromazolam is a triazolam benzodiazepine that recently emerged as a new
      psychoactive substance. Since metabolism data are scarce and good analytical
      targets besides the parent are unknown, we investigated flubromazolam metabolism
      in vitro and in vivo. 10MUmol/L flubromazolam was incubated with human liver
      microsomes for 1h and with cryopreserved human hepatocytes for 5h. Mice were
      administered 0.5 or 1.0mg flubromazolam/kg body weight intraperitoneally, urine
      was collected for 24h. All samples, together with six authentic forensic human
      case specimens, were analyzed (with or without hydrolysis, in case it was urine)
      by UHPLC-HRMS on an Acquity HSS T3 column with an Agilent 6550 QTOF. Data mining
      was performed manually and with MassMetasite software (Molecular Discovery). A
      total of nine metabolites were found, all generated by hydroxylation and/or
      glucuronidation. Besides O-glucuronidation, flubromazolam formed an N+
      glucuronide. Flubromazolam was not metabolized extensively in vitro, as only two
      monohydroxy metabolites were detected in low intensity in hepatocytes. In the
      mice samples, seven metabolites were identified, which mostly matched the
      metabolites in the human samples. However, less flubromazolam N+-glucuronide and
      an additional hydroxy metabolite were observed. The six human urine specimens
      showed different extent of metabolism: some samples had an intense flubromazolam
      peak next to a minute signal for a monohydroxy metabolite, others showed the
      whole variety of hydroxylated and glucuronidated metabolites. Overall, the most
      abundant metabolite was a monohydroxy metabolite, which we propose as alpha
      hydroxyflubromazolam based on MSMS fragmentation. These metabolism data will
      assist in interpretation and analytical method development.

PMID- 27863837
TI  - The effects of ropivacaine hydrochloride on the expression of CaMK II mRNA in the
      dorsal root ganglion neurons.
AB  - In this study, we identified the subtype of Calcium/calmodulin-dependent protein
      kinase II (CaMK II) mRNA in dorsal root ganglion neurons and observed the effects
      of ropivacaine hydrochloride in different concentration and different exposure
      time on the mRNA expression. Dorsal root ganglion neurons were isolated from the
      SD rats and cultured in vitro. The mRNA of the CaMK II subtype in dorsal root
      ganglion neurons were detected by real-time PCR. As well as, the dorsal root
      ganglion neurons were treated with ropivacaine hydrochloride in different
      concentration (1mM,2mM, 3mM and 4mM) for the same exposure time of 4h, or
      different exposure time (0h,2h,3h,4h and 6h) at the same concentration(3mM). The
      changes of the mRNA expression of the CaMK II subtype were observed with real
      time PCR. All subtype mRNA of the CaMK II, CaMK IIalpha, CaMK IIbeta, CaMK II
      delta, CaMK IIgamma, can be detected in dorsal root ganglion neurons. With the
      increased of the concentration and exposure time of the ropivacaine
      hydrochloride, all the subtype mRNA expression increased. Ropivacaine
      hydrochloride up-regulate the CaMK IIbeta, CaMK IIdelta, CaMK IIg mRNA expression
      with the concentration and exposure time increasing. The nerve blocking or the
      neurotoxicity of the ropivacaine hydrochloride maybe involved with CaMK II.

PMID- 27863838
TI  - Resveratrol enhances the efficacy of sorafenib mediated apoptosis in human breast
      cancer MCF7 cells through ROS, cell cycle inhibition, caspase 3 and PARP
      cleavage.
AB  - Despite advances in diagnosis and treatment options, breast cancer is one of the
      main causes of cancer related death among women worldwide. Present study is aimed
      to preliminarily evaluate our hypothesis that the combination of resveratrol
      (RSV), a natural antioxidant, and lower dose of sorafenib (SF), a multi-kinase
      inhibitor and a component of ERK1/2 (extracellular signal-regulated kinase 1/2)
      pathway, would augment apoptosis in human breast cancer MCF7 cells. MCF7
      cellexpressions s were treated with RSV, SF and their combination. MTT (3-[4,5
      dimethylthiazol-2-yl] -2, 5-diphenyl-tetrazolium bromide) assay, DNA
      fragmentation assay, Hoechst33342, H2DCFDA (2', 7'-Dichlorodihydrofluorescein
      diacetate), Rhodamine123 staining, and Western Blot to detect different signaling
      protein expressions, were conducted to test the hypothesis. Combination of RSV
      and SF showed higher cytotoxicity on MCF7 cells than their individual treatment.
      Results from morphology change, Hoechst33342 staining, and DNA fragmentation
      suggested higher apoptosis data in the combinational treatment. Intracellular ROS
      (reactive oxygen species) levels, p53 and Bax/Bcl2 expressions, and decrease in
      mitochondrial membrane potential were also higher in the combinational treatment.
      Up-regulation of apaf-1, cl. caspase 9, cl. caspase 3 and cl. PARP (poly (ADP
      Ribose) polymerase) were also noticed, while the expressions of cyclinD1 and
      cyclinB1 were decreased in the combinational group. The increase in apoptosis and
      signaling protein expressions with RSV and SF combinational treatment were
      increased over time. The combination of RSV and lower dose of SF at 6MUM showed
      enhanced apoptotic activity than SF alone. Therefore, RSV can be considered as a
      neo-adjuvant to improve SF efficacy in breast cancer treatment.

PMID- 27863839
TI  - Antihyperuricemic effect of liquiritigenin in potassium oxonate-induced
      hyperuricemic rats.
AB  - The aim is to investigate the anti-hyperuricemic and renal protective effects of
      liquiritigenin in potassium oxonate-induced hyperuricemic rats. Hyperuricemia in
      rats was induced were induced with potassium oxonate (250mg/kg) intragastrically
      for 7 days, and liquiritigenin (20, 40mg/kg) and allopurinol (5mg/kg) were daily
      administrated to the rats orally 1h after the potassium oxonate exposure.
      Liquiritigenin significantly reversed the elevated productions of uric acid in
      serum and urine and pro-inflammation cytokines in serum and kidney, which shown
      that liquiritigenin has renal protective effects. Histological study shows that
      liquiritigenin inhibited severe necrosis and inflammatory cell infiltration in
      potassium oxonate-treated rats. Furthermore, liquiritigenin mediated the
      activities of aquaporins 4 (AQP4), and regulated the activation of NF-kappaB p65
      and the degradation of IkappaBalpha. Finally, significant increases of nod-like
      receptor protein 3 (NLRP3) inflammasome, apoptosis-associated speck-like protein
      adaptor (ASC) adaptor and cleaved caspased-1 were restored by liquiritigenin.
      Therefore, liquiritigenin might improve renal inflammation by suppressing renal
      AQP4/NF-kappaB/IkappaBalpha and NLRP3 inflammasome activation in hyperuricemic
      rats.

PMID- 27863840
TI  - Long-term pre-treatment of antioxidant Ginkgo biloba extract EGb-761 attenuates
      cerebral-ischemia-induced neuronal damage in aged mice.
AB  - Antioxidant activity has been attributed to the neuroprotective effects of Ginkgo
      biloba extract EGb-761 on brain disorders including ischemic stroke. It is
      suggested that oxidative stress implicates in neuron injuries during aging.
      However, whether or not EGb-761 could be used to treat age-related cerebral
      ischemia is unclear. In the present study, we directly studied the protective
      effects of EGb-761 in brain ischemia in the mice with different age. As expected,
      the recovery from brain damages was impaired in aged mice (24 months) in an
      animal model of middle cerebral artery occlusion (MCAO). Notably, a 12-month
      pretreatment of EGb-761 significantly ameliorated the ischemic injury of aged
      mice in a dose-dependent manner. The decreased stroke severity by EGb-761 was
      suggested by the reduced infarct volumes and brain edema, accompanied by
      alleviated oxidative stress. Additionally, we further explored the potential
      involvement of extra-cellular signal-regulated kinase (ERK) activation by MCAO in
      aged mice. ERK activation after MCAO was diminished by EGb-761, and this
      reduction may be mediated through an upregulation of phosphatase PP2A by EGb-761.
      These observations collectively support that natural antioxidant EGb-761 could be
      potentially exploited as an effective approach in treating neurological injury
      during aging.

PMID- 27863841
TI  - The role and impact of estrogens and xenoestrogen on the development of cervical
      cancer.
AB  - Throughout an individual's lifetime, the human body is exposed to many different
      chemical compounds, including xenoestrogens (XEs) that can be found in the
      environment, food, air, cosmetics and other substances, which have a positive or
      negative impact on their health and lifestyle. Whereas high-risk human
      papillomavirus (HR-HPV) is necessary but not sufficient for full malignant
      cervical cell transformation, other compounds such as estrogens and XEs may be
      risk factors for cervical cancer (CC) development. The causes and effects of some
      diseases such as cancer, cardiovascular, metabolic or immune system disorders are
      partly due to signaling pathways in response to estrogens. XEs are a vast group
      of natural and synthetic compounds, behaving like estrogens, that have been
      studied over the recent years and which may interact with estrogen receptors. The
      major problem with XEs is the difficulty in studying the mechanism of such
      complex substances as well as investigating the influences of some of the
      compounds (dose-dependent) over time. The impact of XEs on CC is variable, with
      no direct comparison between in vitro studies and in vivo XEs action.

PMID- 27863813
TI  - Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479
      population-based measurement studies with 19.1 million participants.
AB  - BACKGROUND: Raised blood pressure is an important risk factor for cardiovascular
      diseases and chronic kidney disease. We estimated worldwide trends in mean
      systolic and mean diastolic blood pressure, and the prevalence of, and number of
      people with, raised blood pressure, defined as systolic blood pressure of 140 mm
      Hg or higher or diastolic blood pressure of 90 mm Hg or higher. METHODS: For this
      analysis, we pooled national, subnational, or community population-based studies
      that had measured blood pressure in adults aged 18 years and older. We used a
      Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic
      and mean diastolic blood pressure, and the prevalence of raised blood pressure
      for 200 countries. We calculated the contributions of changes in prevalence
      versus population growth and ageing to the increase in the number of adults with
      raised blood pressure. FINDINGS: We pooled 1479 studies that had measured the
      blood pressures of 19.1 million adults. Global age-standardised mean systolic
      blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7-128.3) in men
      and 122.3 mm Hg (121.0-123.6) in women; age-standardised mean diastolic blood
      pressure was 78.7 mm Hg (77.9-79.5) for men and 76.7 mm Hg (75.9-77.6) for women.
      Global age-standardised prevalence of raised blood pressure was 24.1% (21.4-27.1)
      in men and 20.1% (17.8-22.5) in women in 2015. Mean systolic and mean diastolic
      blood pressure decreased substantially from 1975 to 2015 in high-income western
      and Asia Pacific countries, moving these countries from having some of the
      highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood
      pressure also decreased in women in central and eastern Europe, Latin America and
      the Caribbean, and, more recently, central Asia, Middle East, and north Africa,
      but the estimated trends in these super-regions had larger uncertainty than in
      high-income super-regions. By contrast, mean blood pressure might have increased
      in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015,
      central and eastern Europe, sub-Saharan Africa, and south Asia had the highest
      blood pressure levels. Prevalence of raised blood pressure decreased in high
      income and some middle-income countries; it remained unchanged elsewhere. The
      number of adults with raised blood pressure increased from 594 million in 1975 to
      1.13 billion in 2015, with the increase largely in low-income and middle-income
      countries. The global increase in the number of adults with raised blood pressure
      is a net effect of increase due to population growth and ageing, and decrease due
      to declining age-specific prevalence. INTERPRETATION: During the past four
      decades, the highest worldwide blood pressure levels have shifted from high
      income countries to low-income countries in south Asia and sub-Saharan Africa due
      to opposite trends, while blood pressure has been persistently high in central
      and eastern Europe. FUNDING: Wellcome Trust.

PMID- 27863842
TI  - Development of T follicular helper cells and their role in disease and immune
      system.
AB  - The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to
      regulate antibody responses. The production of these cells is associated with the
      dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers
      (GC) differentiate into memory and plasma cells (antibody-secreting cells) as
      humoral responses. In addition, there is strong evidence that TFH cells play a
      pivotal role in the development of long-lived humoral immunity. Molecular factors
      such as transcription factors, surface receptors, cytokine and micro RNAs are
      involved in the formation of TFH cells. Such TFH cells are diagnosed by
      transcription factor (BCL-6), surface marker expression (including CXCR5, PD-1,
      ICOS and CD40L) and a unique cytokine production pattern (such as IL-21 and IL
      6). Memory TFH cells, accompanied by memory B cells, are known to be formed
      during antibody responses. It is now clear that the precise control of TFH cells
      is critically important for both inducing the optimal affinity maturation of
      antibody responses and preventing self-reactivity. Exclusive controls of TFH cell
      function and production are essential for human health. However, it is important
      to note that excessive activities may lead to autoimmune diseases, while reduced
      activity often results in immunodeficiency. It has also been shown that TFH cells
      are associated with cancers such as angioimmunoblastic T-cell lymphoma (AITL),
      follicular T-cell lymphoma (FTCL) and nonspecific Peripheral T-cell lymphomas
      (PTCLs). The biology of TFH cells, including their differentiation and
      transcriptional regulation will be described in the present review. Some of The
      developments of these cells in immunodeficiency diseases, autoimmunity and cancer
      will also be taken into account.

PMID- 27863843
TI  - SCORE2 Report 2: Study Design and Baseline Characteristics.
AB  - PURPOSE: To describe the design and baseline characteristics of participants in
      the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) and to
      compare with cohorts from other retinal vein occlusion trials. DESIGN: Phase III
      prospective, multicenter, randomized clinical trial designed to assess whether
      intravitreal bevacizumab is noninferior to intravitreal aflibercept for treatment
      of decreased vision attributable to macular edema associated with central retinal
      vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO). PARTICIPANTS: Total
      of 362 participants: 307 with CRVO and 55 with HRVO. METHODS: Demographic and
      study eye characteristics are summarized and compared between CRVO and HRVO study
      participants. MAIN OUTCOME MEASURES: Baseline ophthalmic characteristics,
      including visual acuity and retinal thickness, and medical history
      characteristics, including hypertension, diabetes mellitus, and coronary artery
      disease. RESULTS: The mean age of participants was 69 years, 76% of participants
      were white, and 90% were non-Hispanic. There was a racial disparity with respect
      to disease type, with 38% of HRVO patients being black compared with 11% of CRVO
      patients (P value adjusted for multiple testing = 0.0001). This is similar to
      findings from the previous SCORE Study. Comorbidities included hypertension
      (77%), diabetes mellitus (31%), and coronary artery disease (15%). At baseline,
      mean visual acuity letter score was 50 (20/100) (range, 19-73 [20/400 to 20/40]),
      mean optical coherence tomography (OCT)-measured central subfield thickness was
      678 MUm (range, 300-1203 MUm), and mean number of months from diagnosis of
      macular edema to randomization was 6 (range, 0-104 months). One hundred twenty
      (33%) SCORE2 participants had been treated previously with anti-vascular
      endothelial growth factor (anti-VEGF) therapy, with these participants having
      baseline visual acuity letter score and OCT-measured central subfield thickness
      similar to those without prior anti-VEGF treatment, but longer mean duration of
      macular edema before randomization (18 months vs. 1 month for those without prior
      anti-VEGF treatment; P < 0.0001). CONCLUSIONS: The SCORE2 cohort is a
      heterogeneous population, including both CRVO and HRVO eyes and both treatment
      naive eyes and eyes treated previously with anti-VEGF, which will allow study
      results to have broad applicability to CRVO and HRVO patients receiving treatment
      for macular edema. Similarities of the baseline characteristics of the SCORE2
      population to other CRVO trial cohorts will allow meaningful comparisons of
      outcome results across trials.

PMID- 27863844
TI  - Persistent Impairment of Quality of Life in Patients with Herpes Simplex
      Keratitis.
AB  - PURPOSE: To evaluate the quality of life (QoL) in patients with quiescent herpes
      simplex keratitis compared with control patients without ocular herpes. DESIGN:
      Prospective, case-control study. PARTICIPANTS: Thirty-three patients with a
      unilateral and relapsing herpes simplex keratitis (HSK group) that was quiescent
      during evaluation (no acute episode in the past 3 months) and 66 patients with no
      history of HSK (control group). Both groups were age and gender matched. METHODS:
      Three previously validated QoL questionnaires were used in this study: the
      National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25), Glaucoma
      Quality of Life 17 (Glau-QoL17) questionnaire, and Ocular Surface Disease Quality
      of Life (OSD-QoL) questionnaire. Each questionnaire covered various aspects of
      the disease. MAIN OUTCOME MEASURES: The outcomes of the 3 questionnaires were
      compared between groups. For the HSK group, the results were correlated to the
      clinical findings and the history of herpetic disease. RESULTS: The mean total
      questionnaire scores of the 3 QoL questionnaires were significantly lower in the
      HSK group compared with controls (NEI VFQ-25: 70.5+/-3.8 vs. 91.1+/-0.8, P <
      0.0001; Glau-QoL17: 68.2+/-3.1 vs. 87.9+/-1.0, P < 0.0001; and OSD-QoL: 65.4+/
      2.9 vs. 93.1+/-0.6, P < 0.0001, respectively). In the HSK group, the level of
      visual acuity (VA) in the affected eye had the greatest impact on QoL, inducing
      lower QoL results related to "general vision," "distance activities,"
      "dependency," "peripheral vision," "self-image," "daily living," and "driving"
      dimensions. Decreased VA in the unaffected eye also negatively affected "self
      image" and "driving" results. Patients with frequent HSK relapses had lower QoL
      related to "ocular pain" and "acknowledgement." CONCLUSIONS: Even during a
      quiescent phase of the disease, unilateral and relapsing HSK significantly
      impairs the QoL of patients to a similar level as most sight-threatening
      diseases. The decrease of VA has the greatest overall effect, but other factors
      also significantly affect QoL, such as the frequency of relapses.

PMID- 27863846
TI  - Chemotherapy and radiation components of neoadjuvant treatment of pancreatic head
      adenocarcinoma: Impact on perioperative mortality and long-term survival.
AB  - BACKGROUND: We compared outcomes of neoadjuvant therapy delivered as chemotherapy
      only (Chemo) versus concurrent chemoradiation (ChemoRT) versus chemotherapy
      followed by radiation (Chemo-ChemoRT) among pancreatic head adenocarcinoma
      patients receiving pancreaticoduodenectomy. METHODS: National Cancer Data Base
      cases diagnosed 2006-2011 treated by neoadjuvant therapy and
      pancreaticoduodenectomy. RESULTS: 1163 pts received neoadjuvant treatment with
      Chemo (n = 309; 26.6%), ChemoRT (n = 626; 53.8%), or Chemo-ChemoRT (n = 228;
      19.6%). Odds of 30-day and 90-day mortality were not influenced by delivery of
      any neoadjuvant therapy type. Median overall survival for Chemo, ChemoRT, and
      Chemo-ChemoRT groups were 25.6 (95% confidence interval 23.1-28.7), 22.9 (21.4
      24.8), and 26.9 (23.7-29.4) months, respectively. There was no statistically
      significant difference between Chemo and Chemo-ChemoRT groups (log rank test p =
      0.854), while there was significant difference of ChemoRT (p = 0.017 versus
      Chemo; p = 0.021 versus Chemo-ChemoRT). Multivariate model suggests delivery of
      concurrent ChemoRT as opposed to neoadjuvant therapy with full dose systemic
      chemotherapy is associated with shortened survival (aHR = 1.311, p = 0.001).
      CONCLUSIONS: There is no detectable difference in early outcomes (30-day and 90
      day postsurgical mortality) among pancreaticoduodenectomy patients treated with
      various types of neoadjuvant therapy. Overall survival appears better among
      patients exposed preoperatively to full dose systemic chemotherapy rather than
      concurrent chemoradiation only. Further studies with more detailed data sources
      are needed.

PMID- 27863845
TI  - Macular Atrophy in Neovascular Age-Related Macular Degeneration with Monthly
      versus Treat-and-Extend Ranibizumab: Findings from the TREX-AMD Trial.
AB  - PURPOSE: To compare the enlargement rate of macular atrophy (ERMA) in eyes
      treated with ranibizumab monthly or using a treat-and-extend (TREX) regimen for
      neovascular age-related macular degeneration (AMD) or fellow control eyes, as
      well as analyze risk factors for macular atrophy (MA) development and
      progression. DESIGN: Eighteen-month, multicenter, randomized, controlled clinical
      trial. PARTICIPANTS: Sixty patients with treatment-naive neovascular AMD in 1 eye
      randomized 1:2 to monthly or TREX ranibizumab. METHODS: Patients' study and
      fellow eyes were followed for 18 months using spectral-domain optical coherence
      tomography (SD OCT) and fundus autofluorescence (FAF) imaging. The MA was
      quantified on FAF images using Heidelberg Region Finder software (Heidelberg
      Engineering, Heidelberg, Germany), with suspected areas of atrophy confirmed by
      SD OCT and infrared reflectance imaging. For eyes without baseline MA yet
      developed MA by 18 months, intervening visits were assessed to determine the
      first visit at which MA appeared to define progression rates. Foveal choroidal
      thickness (FCT), subretinal hyperreflective material (SHRM), and pigment
      epithelial detachment (PED), were assessed at baseline to determine whether they
      influenced MA progression. MAIN OUTCOME MEASURES: Mean ERMA at 18 months.
      Relationship between visual acuity and MA, and the baseline risk factors for ERMA
      were also assessed. RESULTS: The final analysis cohort included 88 eyes in 3
      groups: monthly (n = 19), TREX (n = 30), and control fellow eyes (n = 39). Mean
      ERMA over 18 months was 0.39+/-0.67 (monthly), 1.1+/-1.9 (TREX), and 0.49+/-1 mm2
      (control, P = 0.12). Mean ERMA per group among the 40.9% (n = 36) of baseline
      patients with MA was 0.9+/-1, 1.9+/-2.2, and 1+/-1.3 mm2, respectively (P =
      0.31). The incidence rate of MA in the 3 groups was 40%, 0%, and 8.3%,
      respectively. Mann-Whitney U test revealed a statistically significant
      association between baseline FCT (127+/-46 vs. 155+/-55 MUm, P = 0.01) and SHRM
      thickness (106+/-131 vs. 50+/-85 MUm, P = 0.02) on MA. In eyes with no baseline
      MA, presence of SHRM, SHRM, and PED thickness, and presence of baseline
      hemorrhage were all significant predictors of new MA development (P = 0.04, 0.01,
      0.04, 0.004, 0.01, respectively). CONCLUSIONS: Ranibizumab did not show a
      statistically significant influence on new MA development in eyes with
      neovascular AMD, whether dosed monthly or per TREX regimen. The FCT, SHRM
      thickness, and hemorrhage at baseline were all significant predictors of new MA.

PMID- 27863847
TI  - Parental Attitudes About Placebo Use in Children.
AB  - OBJECTIVE: To assess parental attitudes regarding placebo use in pediatric
      randomized controlled trials and clinical care. STUDY DESIGN: Parents with
      children under age 18 years living in the US completed and submitted an online
      survey between September and November 2014. RESULTS: Among all 1300 participants,
      1000 (76.9%; 538 mothers and 462 fathers) met the study inclusion criteria. The
      majority of surveyed parents considered the use of placebos acceptable in some
      pediatric care situations (86%) and some pediatric trials (91.5%), whereas only
      5.7% of parents found the use of placebos in children always unacceptable. The
      clinical use of placebo was considered acceptable by a majority of parents for
      only 7 (mostly psychological) of the 17 conditions presented. Respondents'
      judgment about acceptability was influenced by the doctors' opinions about the
      therapeutic benefits of placebo treatment, the conditions for pediatric placebo
      use, transparency, safety, and purity of placebos. CONCLUSION: Most surveyed
      parents accepted the idea of using placebos in pediatric trials and within the
      clinic for some conditions without the practice of deception and with the
      creation of guidelines for ethical and safe use. This study suggests a need to
      reconsider pediatric trial design and clinical therapy in the light of generally
      positive parental support of appropriate placebo use.

PMID- 27863848
TI  - Hypermobility and Musculoskeletal Pain in Adolescents.
AB  - OBJECTIVE: To determine the prevalence of generalized joint hypermobility (GJH)
      in a large cohort of Australian children and determine the associations between
      GJH and musculoskeletal pain. STUDY DESIGN: This is a cross-sectional analysis of
      the Western Australian Pregnancy Cohort (Raine) Study. Hypermobility was measured
      in 1584 participants at 14 years of age using the Beighton scoring system, along
      with a range of other factors including musculoskeletal pain status. Logistic
      regression models were used to assess independent associations of GJH with
      factors of interest. RESULTS: The prevalence of GJH was 60.6% and 36.7% in girls
      and boys, respectively, when defined as a Beighton score of >=4; when defined as
      >=6, it was 26.1% and 11.5%. In girls, positive associations between GJH and
      higher socioeconomic status and better motor competence were observed. In boys,
      positive associations between GJH and lower body mass index were observed. After
      adjusting for potential confounders, an association between number of pain areas
      in the last month and made worse with sport were identified in boys but not
      girls. CONCLUSION: The high prevalence rates of GJH as defined by commonly used
      Beighton cutoff values in this cohort highlight the need to question the
      appropriateness of these cutoffs in future studies. Future prospective studies of
      the association between GJH and musculoskeletal pain should be adjusted for
      confounding variables identified in this study, and be powered for sex-specific
      analyses owing to the differing prevalence rates and hypermobility correlates in
      male and female samples.

PMID- 27863849
TI  - Nasogastric Tube in the Right Hemithorax: Where Is It?

PMID- 27863850
TI  - Pediatric Concussion Management in the Emergency Department: A National Survey of
      Parents.
AB  - OBJECTIVE: To examine parental expectations and beliefs about diagnosis and
      management of pediatric concussion. STUDY DESIGN: We conducted a cross-sectional
      web-based survey of a nationally representative panel of US parents in March
      2014. Parents of 10- to 17-year-old children responded to questions about their
      expectations and beliefs about diagnosis and management of pediatric concussion
      in the emergency department (ED). Weighted percentages for descriptive statistics
      were calculated, and chi2 statistics were used for bivariate analysis. RESULTS:
      Survey participation was 53%, and of 912 parent respondents with a child 10-17
      years of age who were presented with a scenario of their child having mild
      symptoms of concussion, 42% would seek immediate ED care. Parents who would seek
      immediate ED care for this scenario were more likely than parents who would
      consult their child's usual provider or wait at home to "definitely expect"
      imaging (65% vs 21%), definitive diagnosis of concussion (77% vs 61%), a timeline
      for return to activity (80% vs 60%), and a signed return to play form (55% vs
      41%). CONCLUSIONS: Many parents who bring children to the ED following a possible
      concussion are likely to expect comprehensive and definitive care, including
      imaging, a definitive diagnosis, a timeline for return to activity, and a signed
      return to play form. To manage these expectations, healthcare providers should
      continue to educate parents about the evaluation and management of concussion.

PMID- 27863851
TI  - Long-term exposition to a high fat diet favors the appearance of beta-amyloid
      depositions in the brain of C57BL/6J mice. A potential model of sporadic
      Alzheimer's disease.
AB  - AIMS: The sporadic and late-onset form of Alzheimer's disease (AD) constitutes
      the most common form of dementia. This non-familiar form could be a consequence
      of metabolic syndrome, characterized by obesity and the development of a brain
      specific insulin resistance known as type III diabetes. This work demonstrates
      the development of a significant AD-like neuropathology due to these metabolic
      alterations. METHODS: C57BL/6J mice strain were divided into two groups, one fed
      with a diet rich in palmitic acid (high-fat diet, HFD) since their weaning until
      16 months of age, and another group used as a control with a regular diet. The
      analyses were carried out in the dentate gyrus area of the hippocampus using a
      Thioflavin-S stain and immunofluorescence assays. RESULTS: The most significant
      finding of the present research was that HFD induced the deposition of the betaA
      peptide. Moreover, the diet also caused alterations in different cell processes,
      such as increased inflammatory reactions that lead to a decrease in the neuronal
      precursor cells. In addition, the results show that there were also
      dysregulations in normal autophagy and apoptosis, mechanisms related to betaA
      formation. CONCLUSIONS: The present findings confirm that HFD favors the
      formation of betaA depositions in the brain, a key feature of AD, supporting the
      metabolic hypothesis of sporadic AD.

PMID- 27863852
TI  - The RAG recombinase: Beyond breaking.
AB  - DNA double-strand breaks (DSBs) are commonly seen as lesions that threaten genome
      integrity and contribute to cancer and aging processes. However, in the context
      of antigen receptor gene assembly, known as V(D)J recombination, DSBs are
      obligatory intermediates that allow the establishment of genetic diversity and
      adaptive immunity. V(D)J recombination is initiated when the lymphoid-restricted
      recombination-activating genes RAG1 and RAG2 are expressed and form a site
      specific endonuclease (the RAG nuclease or RAG recombinase). Here, we discuss the
      ability of the RAG nuclease to minimize the risks of genome disruption by
      coupling the breakage and repair steps of the V(D)J reaction. This implies that
      the RAG genes, derived from an ancient transposon, have undergone strong
      selective pressure to prohibit transposition in favor of promoting controlled DNA
      end joining in cis by the ubiquitous DNA damage response and DNA repair
      machineries. We also discuss the idea that, in addition to being essential for
      the rearrangement of antigen receptor genes, RAG-mediated DSBs could impact
      cellular processes and outcomes by affecting genetic and epigenetic programs.

PMID- 27863853
TI  - Balancing Inflammation: Computational Design of Small-Molecule Toll-like Receptor
      Modulators.
AB  - As essential proteins of the innate immune system, Toll-like receptors (TLRs) are
      involved in a plethora of physiological pathologies and their modulation is an
      ongoing quest in the field of drug discovery. Although TLRs recognize an
      unusually broad range of different molecular patterns, only a few small-molecule
      TLR modulators have been reported to date. Recent advances in crystallography and
      in silico techniques provide promising opportunities for TLR investigations and
      drug design. Here, three application areas for computational approaches are
      considered: (i) exploration of TLR structure and activation; (ii) understanding
      TLR modulation; and (iii) TLR drug discovery. By providing an overview on state
      of-the-art computational methods, we highlight the value of molecular modeling in
      mechanistically understanding TLR function and guiding drug design.

PMID- 27863854
TI  - The Various Metabolic Sources of Histone Acetylation.
AB  - Glucose-derived acetyl-CoA levels directly impact histone acetylation, linking
      the energetic status of the cell to its epigenome. Two recent reports showed that
      other carbon sources can contribute to the acetyl-CoA pool used for histone
      acetylation, highlighting the metabolic plasticity that allows cells to respond
      to nutrient availability.

PMID- 27863856
TI  - Accuracy of intraoral digital impressions using an artificial landmark.
AB  - STATEMENT OF PROBLEM: Intraoral scanners have been reported to have limited
      accuracy in edentulous areas. Large amounts of mobile tissue and the lack of
      obvious anatomic landmarks make it difficult to acquire a precise digital
      impression of an edentulous area with an intraoral scanner. PURPOSE: The purpose
      of this in vitro study was to determine the effect of an artificial landmark on a
      long edentulous space on the accuracy outcomes of intraoral digital impressions.
      MATERIAL AND METHODS: A mandibular model containing 4 prepared teeth and an
      edentulous space of 26 mm in length was used. A blue-light light-emitting diode
      tabletop scanner was used as a control scanner, and 3 intraoral scanners were
      used as experimental groups. Five scans were made using each intraoral scanner
      without an artificial landmark, and another 5 scans were performed after
      application of an artificial landmark (a 4*3 mm alumina material) on the
      edentulous area. The obtained datasets were used to evaluate trueness and
      precision. RESULTS: Without an artificial landmark on the edentulous area, the
      mean trueness for the intraoral scanner ranged from 36.1 to 38.8 MUm and the mean
      precision ranged from 13.0 to 43.6 MUm. With an artificial landmark on the
      edentulous area, accuracy was improved significantly: the mean trueness was 26.7
      to 31.8 MUm, and the mean precision was 9.2 to 12.4 MUm. CONCLUSIONS: The use of
      an alumina artificial landmark in an edentulous space improved the trueness and
      precision of the intraoral scanners tested.

PMID- 27863855
TI  - Erratum to "Intra-individual changes in Stroop-related activations linked to
      cigarette abstinence in adolescent tobacco smokers: Preliminary findings" [Drug
      Alcohol Depend. 167 (2016) 182-189].

PMID- 27863857
TI  - Retention and wear behaviors of two implant overdenture stud-type attachments at
      different implant angulations.
AB  - STATEMENT OF PROBLEM: Implant angulation should be considered when selecting an
      attachment. Some in vitro studies have investigated the relationship between
      implant angulation and changes in the retention force of the stud attachment, but
      few studies have evaluated the effect of cyclic loading and repeated cycles of
      insertion and removal on the stud attachment. PURPOSE: The purpose of this in
      vitro study was to evaluate the effects of implant angulation on the retentive
      characteristics of overdentures with 2 different stud attachments, an
      experimental system and O-rings in red and orange, after cyclic loading and
      repeated insertion and removal cycles. MATERIAL AND METHODS: The canine region of
      a mandibular experimental model was fitted with 2 implant fixtures with 2
      different stud attachment systems at implant angulations of 0, 15, or 30 degrees.
      A mastication simulator was used to simulate cyclic loading, and a universal
      testing machine was used to evaluate retentive force changes after repeated
      insertion and removal cycles. To simulate the numbers of mastication and
      insertion and removal cycles per annum, 400000 cyclic loadings and 1080 insertion
      and removal cycles were performed. Wear patterns and attachment surface
      deformations were evaluated by scanning electron microscopy. Data were analyzed
      using the Kruskal-Wallis test, Mann-Whitney U test with Bonferroni correction
      (alpha=.05/3=.017), and the paired-sample Student t test (alpha=.05). RESULTS:
      When retentive forces before and after testing were compared, O-ring showed
      significant retention loss at all implant angulations (P<.001). In contrast, the
      experimental system showed little retention loss in the 0- and 15-degree models
      (P>.05), whereas the 30-degree model showed a significant increase in retentive
      force (P=.001). At all implant angulations, retention loss increased
      significantly for the orange O-ring, followed by the red O-ring, and the
      experimental system (P<.001). Scanning electron microscopy analysis showed more
      intense wear in the matrix than the patrix (abutment that matches to matrix) and
      more severe wear and deformation of the O-ring rubber matrix than of the
      experimental zirconia ball. CONCLUSIONS: Upon completion of the experiment, wear
      and deformation were found for all attachment systems. Even when implants are not
      installed in parallel, the experimental system can be used without involving
      great loss of retention.

PMID- 27863858
TI  - Authors' Response.

PMID- 27863859
TI  - Effect of fiber posts on the fracture resistance of maxillary central incisors
      with Class III restorations: An in vitro study.
AB  - STATEMENT OF PROBLEM: Endodontically treated teeth with Class III restorations
      show reduced fracture resistance. The placement of glass fiber posts may affect
      fracture resistance and should be further evaluated. PURPOSE: The purpose of this
      in vitro study was to evaluate the effect of fiber posts on the fracture
      resistance of endodontically treated maxillary central incisors with Class III
      restorations. MATERIAL AND METHODS: Forty extracted human maxillary central
      incisors were selected and divided into 4 test groups (n=10 each) according to
      the restoration strategy: control group; endodontically treated teeth without
      endodontic posts (GHT); endodontically treated teeth with 2 Class III
      restorations simulating coronal destruction (GCT); endodontically treated teeth
      with 2 Class III restorations and a carbon fiber post (GCF); and endodontically
      treated teeth with 2 Class III restorations and a glass-fiber post (GGF). The
      fiber posts were adhesively cemented with composite resin cement, and the
      cavities were restored with composite resin. After 3 months of water storage, all
      specimens were loaded at 45 degrees in a universal testing machine until fracture
      and evaluated for fracture mode. The data were analyzed using 1-way ANOVA,
      followed by the Tukey honest significant difference multiple comparisons test
      (alpha=.05). RESULTS: Mean +/-SD failure loads ranged from 687.5 +/-84.0 N to
      943.8 +/-93.1 N. One-way ANOVA revealed a statistically significant difference
      among the groups (P<=.05). The control group (GHT) had significantly higher
      resistance to fracture than the other groups (P<=.05). CONCLUSIONS: Within the
      limitations of this in vitro study, placement of a fiber post did not affect the
      fracture resistance of endodontically treated maxillary central incisors with 2
      Class III restorations.

PMID- 27863860
TI  - Orofacial rehabilitation with zygomatic implants: CAD-CAM bar and magnets for
      patients with nasal cancer after rhinectomy and partial maxillectomy.
AB  - Nasal carcinoma extending into the premaxilla requires radical surgical excision
      including rhinectomy and partial maxillectomy. Rehabilitation is complex and
      involves the use of removable prostheses. Three patients treated with zygomatic
      implants and custom-milled bars to retain an obturator and nasal prosthesis are
      presented.

PMID- 27863861
TI  - Health care utilization and consequences of readmission in the first year after
      lung transplantation.
AB  - BACKGROUND: Hospital readmissions are costly and have become a focus for quality
      improvement. We aimed to determine risk factors, rate, and outcomes of
      readmissions within the first year after lung transplantation and the potential
      impact on patient survival. METHODS: A retrospective cohort study of all lung
      transplant recipients >=18 years old who had undergone initial transplantation
      (2004-2013) at a single center was conducted. Logistic regression was used to
      identify independent predictors of readmission for patients who survived
      hospitalization. Cox regression was used to explore the relationship between
      readmission and long-term risk of death, while adjusting for potential
      confounders for patients who survived the first year. RESULTS: During the study
      period, 412 patients met inclusion criteria for the readmission analysis. There
      were 276 patients (67%) readmitted within 1 year after lung transplantation for a
      total of 609 readmissions (average +/- SD, 1.5 +/- 2). Average length of
      readmission stay was 6 days +/- 7, with 44% of readmissions lasting <=3 days.
      Airway complications were found to be a significant risk factor for readmission
      (odds ratio, 4.18; 95% confidence interval, 1.78-9.54; p = 0.001). After
      adjustment, the overall risk of death was significantly higher with each
      readmission during the first year (hazard ratio, 1.22; 95% confidence interval,
      1.13-1.31, p < 0.0001). CONCLUSIONS: Most patients who survive the first post
      operative year experience at least 1 readmission, with patients who experience
      airway complications at particular risk. Patients discharged to inpatient
      rehabilitation were less likely to be readmitted. The cumulative burden of
      multiple readmissions is associated with worse long-term survival.

PMID- 27863862
TI  - Extracorporeal membrane oxygenation with multiple-organ failure: Can molecular
      adsorbent recirculating system therapy improve survival?
AB  - BACKGROUND: Liver dialysis, molecular adsorbent recirculating system (MARS)
      particularly, has been used in liver failure to bridge to transplantation. We
      expanded the indication for MARS to patients with acute shock liver failure and
      cardiopulmonary failure on extracorporeal membrane oxygenation (ECMO), aiming to
      improve survival to wean from ECMO. METHODS: Retrospective chart analysis of
      patients on ECMO between 2010 and 2015 found 28 patients who met the criteria for
      acute liver failure, diagnosed by hyperbilirubinemia (total bilirubin >=10 mg/dl)
      or by elevated transaminase (alanine transaminase >1,000 IU/liter). Of these
      patients, 14 underwent MARS treatment (Group M), and 14 were supported with
      optimal medical treatment without MARS (Group C). Patient characteristics, liver
      function, and survival were compared between groups. RESULTS: Demographics,
      clinical risk factors, and pre-ECMO laboratory data were identical between the
      groups. MARS was used continuously for 8 days +/- 9 in Group M. Total bilirubin,
      alanine transaminase, and international normalized ratio were improved
      significantly in Group M. There were no MARS-related complications. Survival to
      wean from ECMO for Group M was 64% (9/14) vs 21% (3/14) for Group C (p = 0.02).
      Mortality related to worsening liver dysfunction during ECMO was 40% (2/5 deaths)
      in Group M and 100% (11/11 deaths) in Group C (p = 0.004). The 30-day survival
      after ECMO was 43% (6/14) in Group M and 14% (2/14) in Group C (p = 0.09).
      CONCLUSIONS: MARS therapy in patients on ECMO safely accelerated recovery of
      liver function and improved survival to wean from ECMO, without increasing
      complications.

PMID- 27863863
TI  - Effect of beta2-adrenergic receptor stimulation on lung fluid in stable heart
      failure patients.
AB  - BACKGROUND: The purpose of this study was to determine: (1) whether stable heart
      failure patients with reduced ejection fraction (HFrEF) have elevated
      extravascular lung water (EVLW) when compared with healthy control subjects; and
      (2) the effect of acute beta2-adrenergic receptor (beta2AR) agonist inhalation on
      lung fluid balance. METHODS: Twenty-two stable HFrEF patients and 18 age- and
      gender-matched healthy subjects were studied. Lung diffusing capacity for carbon
      monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), pulmonary
      capillary blood volume (Vc) (via re-breathe) and lung tissue volume (Vtis) (via
      computed tomography) were assessed before and within 30 minutes after
      administration of nebulized albuterol. EVLW was derived as Vtis - Vc. RESULTS:
      Before administration of albuterol, Vtis and EVLW were higher in HFrEF vs control
      (998 +/- 200 vs 884 +/- 123 ml, p = 0.041; and 943 +/- 202 vs 802 +/- 133 ml, p =
      0.015, respectively). Albuterol decreased Vtis and EVLW in HFrEF patients (-4.6
      +/- 7.8%, p = 0.010; -4.6 +/- 8.8%, p = 0.018) and control subjects (-2.8 +/-
      4.9%, p = 0.029; -3.0 +/- 5.7%, p = 0.045). There was an inverse relationship
      between pre-albuterol values and pre- to post-albuterol change for EVLW (r2 = 
      0.264, p = 0.015) and DmCO (r2 = -0.343, p = 0.004) in HFrEF only. CONCLUSION:
      Lung fluid is elevated in stable HFrEF patients relative to healthy subjects.
      Stimulation of beta2ARs may cause fluid removal in HFrEF, especially in patients
      with greater evidence of increased lung water at baseline.

PMID- 27863864
TI  - Laminin-5 and insulin-like growth factor-II mRNA binding protein-3 (IMP3)
      expression in preoperative biopsy specimens from oral cancer patients: Their role
      in neural spread risk and survival stratification.
AB  - Perineural invasion (PNI) hinders the ability to establish local control of oral
      squamous cell carcinoma (OSCC). To date, PNI can be evaluated only in surgical
      specimens and not in preoperative biopsy material, rendering timely therapeutic
      planning impossible. Insulin-like growth factor-II mRNA binding protein-3 (IMP3)
      expression appears to be of diagnostic and prognostic utility for many solid
      tumours, and laminin-5 expression in surgical specimens has been identified as a
      valid predictor of neural spread of head-and-neck neoplasms. The ability to use
      preoperative biopsy material to identify patients exhibiting PNI is fundamental
      for good management of OSCC. We examined a series of 64 consecutive patients
      treated (primarily via surgery) for OSCC between 2009 and 2014 at the
      Maxillofacial Surgery Unit, University of Bologna. We evaluated IMP3 and laminin
      5 expression in preoperative biopsy material using immunohistochemistry and
      quantitative reverse transcription polymerase chain reaction. We sought to
      correlate expression of IMP3 and laminin-5 with PNI evident in surgical
      specimens. Expression of IMP3 and laminin-5 in preoperative biopsy material
      appeared to be predictive of PNI in patients with OSCC (P < 0.001). Additionally,
      the results of multivariate analyses showed that IMP3 status was an independent
      predictor of death of patients with OSCC (P = 0.001). The present study
      demonstrates that IMP3 and laminin-5 expression in preoperative biopsy material
      correlate well with PNI status and may allow accurate preoperative risk
      stratification of patients with OSCC.

PMID- 27863866
TI  - Insights into bedrock surface morphology using low-cost passive seismic surveys
      and integrated geostatistical analysis.
AB  - The HVSR (Horizontal to Vertical Spectral Ratio) technique is very popular in the
      context of seismic microzonation and for the mapping of shallow seismic
      reflectors, such as the sediment/bedrock transition surface. This easy-to-deploy
      single station passive seismic technique permits the collection of a considerable
      amount of HVSR data in a cost-effective way. It is not surprising that some
      recent studies have adopted single station micro-tremor analyses in order to
      retrieve information on geological structures in 1D, 2D or even 3D
      reconstructions. However, the interpolation approaches followed in these studies
      for extending the punctual HVSR data spatially are not supported by a detailed
      spatial statistical analysis. Conversely, in order to exploit the informative
      content and quantify the related uncertainty of HVSR data it is necessary to
      utilize a deep spatial statistical analysis and objective interpolation
      approaches. Moreover, the interpolation approach should make it possible to use
      expert knowledge and auxiliary information. Accordingly, we present an integrated
      geostatistical approach applied to HVSR data, collected for retrieving
      information on the morphology of a buried bedrock surface. The geostatistical
      study is conducted on an experimental dataset of 116 HVSR data collected in a
      small thermal basin located in the Venetian Plain (Caldiero Basin, N-E Italy).
      The explorative geostatistical analysis of the data coupled with the use of
      interpolation kriging techniques permit the extraction of relevant information on
      the resonance properties of the subsoil. The utilized approach, based on kriging
      with external drift (or its extension, i.e. regression kriging), permits the
      researcher to take into account auxiliary information, evaluate the related
      prediction uncertainty, and highlight abrupt variations in subsoil resonance
      frequencies. The results of the analysis are discussed, also with reflections
      pertaining to the geo-engineering and geo-environmental context.

PMID- 27863865
TI  - Solubility of indium-tin oxide in simulated lung and gastric fluids: Pathways for
      human intake.
AB  - From being a metal with very limited natural distribution, indium (In) has
      recently become disseminated throughout the human society. Little is known of how
      In compounds behave in the natural environment, but recent medical studies link
      exposure to In compounds to elevated risk of respiratory disorders. Animal tests
      suggest that exposure may lead to more widespread damage in the body, notably the
      liver, kidneys and spleen. In this paper, we investigate the solubility of the
      most widely used In compound, indium-tin oxide (ITO) in simulated lung and
      gastric fluids in order to better understand the potential pathways for metals to
      be introduced into the bloodstream. Our results show significant potential for
      release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal
      fluid) and digestive tract, while the solubility in the upper parts of the lungs
      (the respiratory tract or tracheobronchial tree) is very low. Our study confirms
      that ITO is likely to remain as solid particles in the upper parts of the lungs,
      but that particles are likely to slowly dissolve in the deep lungs. Considering
      the prolonged residence time of inhaled particles in the deep lung, this
      environment is likely to provide the major route for uptake of In and Sn from
      inhaled ITO nano- and microparticles. Although dissolution through digestion may
      also lead to some uptake, the much shorter residence time is likely to lead to
      much lower risk of uptake.

PMID- 27863867
TI  - Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and
      birth size: The Hokkaido study on environment and children's health.
AB  - Di-2-ethylhexyl phthalate (DEHP) is one of the most widely used phthalates.
      Metabolites of DEHP are detectable in majority of the population. Findings on
      adverse health outcomes, particularly birth weight in association with prenatal
      exposure to DEHP remain equivocal. Besides, there is insufficient evidence to
      address influence on metabolic function from epidemiological studies. Thus, our
      objective was to investigate cord blood adipokine levels and birth size in
      association with prenatal DEHP exposure in prospective birth cohort study. Mono-2
      methylhexyl phthalate (MEHP), primary metabolite of DEHP was determined as
      exposure by using maternal blood sample of 3rd trimester. Leptin and adiponectin
      levels in cord blood were measured as markers of metabolic function. Birth weight
      and length were obtained from birth record. Association between maternal MEHP
      levels and cord blood adiponectin and leptin levels, birth weight and ponderal
      index (PI) were examined for 167 mother-child pairs who had both MEHP and cord
      blood adipokine measurements. The median MEHP level was 8.81ng/ml and the
      detection rate was 100%. There was no sex difference in MEHP levels. Both leptin
      and adiponectin levels were higher in girls than in boys. MEHP level was
      positively associated with adiponectin level among boys and was negatively
      associated with leptin level among girls. MEHP level were negatively associated
      with PI only in girls and this could be due to decreased leptin level. This study
      suggested that prenatal DEHP exposure may be associated with cord blood adipokine
      and birth size. The influence potentially be sex-specific and could be more
      significant in girls.

PMID- 27863868
TI  - Establishing geochemical background variation and threshold values for 59
      elements in Australian surface soil.
AB  - During the National Geochemical Survey of Australia over 1300 top (0-10cm depth)
      and bottom (~60-80cm depth) sediment samples (including ~10% field duplicates)
      were collected from the outlet of 1186 catchments covering 81% of the continent
      at an average sample density of 1 site/5200km2. The <2mm fraction of these
      samples was analysed for 59 elements by ICP-MS following an aqua regia digestion.
      Results are used here to establish the geochemical background variation of these
      elements, including potentially toxic elements (PTEs), in Australian surface
      soil. Different methods of obtaining geochemical threshold values, which
      differentiate between background and those samples with unusually high element
      concentrations and requiring attention, are presented and compared to Western
      Australia's 'ecological investigation levels' (EILs) established for 14 PTEs. For
      Mn and V these EILs are so low that an unrealistically large proportion (~24%) of
      the sampled sites would need investigation in Australia. For the 12 remaining
      elements (As, Ba, Cd, Co, Cr, Cu, Hg, Mo, Ni, Pb, Sn and Zn) few sample sites
      require investigation and as most of these are located far from human activity
      centres, they potentially suggest either minor local contamination or mineral
      exploration potential rather than pollution. No major diffuse source of
      contamination by PTEs affects Australian soil at the continental scale. Of the
      statistical methods used to establish geochemical threshold values, the most
      pertinent results come from identifying breaks in cumulative probability
      distributions, the Tukey inner fence and the 98th percentile. Geochemical
      threshold values for 59 elements, including emerging 'high-tech' critical
      elements such as lanthanides, Be, Ga or Ge, for which no EILs currently exist,
      are presented.

PMID- 27863869
TI  - Similarities and differences in occurrence and temporal fluctuations in
      glyphosate and atrazine in small Midwestern streams (USA) during the 2013 growing
      season.
AB  - Glyphosate and atrazine are the most intensively used herbicides in the United
      States. Although there is abundant spatial and temporal information on atrazine
      occurrence at regional scales, there are far fewer data for glyphosate, and
      studies that compare the two herbicides are rare. We investigated temporal
      patterns in glyphosate and atrazine concentrations measured weekly during the
      2013 growing season in 100 small streams in the Midwestern United States.
      Glyphosate was detected in 44% of samples (method reporting level 0.2MUg/L);
      atrazine was detected above a threshold of 0.2MUg/L in 54% of samples. Glyphosate
      was detected more frequently in 12 urban streams than in 88 agricultural streams,
      and at concentrations similar to those in streams with high agricultural land use
      (>40% row crop) in the watershed. In contrast, atrazine was detected more
      frequently and at higher concentrations in agricultural streams than in urban
      streams. The maximum concentration of glyphosate measured at most urban sites
      exceeded the maximum atrazine concentration, whereas at agricultural sites the
      reverse was true. Measurement at a 2-day interval at 8 sites in northern Missouri
      revealed that transport of both herbicide compounds appeared to be controlled by
      spring flush, that peak concentration duration was brief, but that peaks in
      atrazine concentrations were of longer duration than those of glyphosate. The 2
      day sampling also indicated that weekly sampling is unlikely to capture peak
      concentrations of glyphosate and atrazine.

PMID- 27863870
TI  - Fast and slow adsorption of carbamazepine on biochar as affected by carbon
      structure and mineral composition.
AB  - The influence of carbon structure and mineral composition of biochar on fast
      adsorption and slow adsorption of ionic organic contaminants (IOCs) is still
      unclear. This study used carbamazepine (CBZ) as adsorbate, peanut-shell-derived
      biochars produced at different charred temperatures, and the corresponding acid
      washed biochars as adsorbents, to investigate the adsorption kinetics as affected
      by carbon structure and mineral composition of biochar. The adsorption of CBZ on
      amorphous (loose) carbon was lower than aromatic (condensed) carbon, but the
      former mainly contributed to the fast adsorption of CBZ. The hydrophobic and pi
      pi interactions were likely the predominant adsorption mechanisms of CBZ on
      biochar. The ratio of CBZ fast and slow adsorption fractions (ffast/fslow)
      significantly reduced after acid-wash treatment of the biochars. The X-ray
      diffraction and Fourier transform infrared spectra indicated that minerals,
      including CaCO3, KAlO2, and quartz, were likely responsible for the fast
      adsorption of CBZ by the hydrogen bonds between CBZ and -OH on the surface of
      minerals. These results are useful for better understanding of the environmental
      behavior and prediction of the environmental risks of IOCs in biochar-amended
      soils.

PMID- 27863871
TI  - Bacterial mineralization of phenanthrene on thermally activated palygorskite: A
      14C radiotracer study.
AB  - Clay-bacterial interaction can significantly influence the biodegradation of
      organic contaminants in the environment. A moderate heat treatment of
      palygorskite could alter the physicochemical properties of the clay mineral and
      thus support the growth and function of polycyclic aromatic hydrocarbon (PAH)
      degrading bacteria. By using 14C-labelled phenanthrene and a model bacterium
      Burkholderia sartisoli, we studied the mineralization of phenanthrene on the
      surface of a moderately heat-treated (up to 400 degrees C) palygorskite. The heat
      treatment at 400 degrees C induced a reduction of binding sites (e.g., by the
      elimination of organic matter and/or channel shrinkage) in the palygorskite and
      thus imparted a weaker sequestration of phenanthrene on its surface and within
      the pores. As a result, a supplement with the thermally modified palygorskite
      (400 degrees C) significantly increased (20-30%; p<0.05) the biomineralization of
      total phenanthrene in a simulated soil slurry system. These results are highly
      promising to develop a clay mineral based technology for the bioremediation of
      PAH contaminants in water and soil environments.

PMID- 27863873
TI  - A Case of Transient Global Amnesia with Small Left Putamen Infarction.
AB  - A 67-year-old right-handed woman experienced a sudden anterograde and retrograde
      short-term memory deficit that recovered on the next day. Magnetic resonance
      imaging (MRI) showed a spotty high-intensity lesion in the left putamen in the
      diffusion-weighted and fluid-attenuated inversion recovery images. Transient
      global amnesia due to lacunar infarction of the left putamen was diagnosed.
      Transient global amnesia is characterized by a sudden onset of anterograde
      amnesia that disappears within 24 hours. The cause of transient global amnesia is
      still uncertain. Some studies with MRI showed small lesions in the hippocampus at
      24-74 hours after the episode. These lesions disappear within several weeks.
      However, our case of transient global amnesia showed a small lesion in the left
      putamen, not the hippocampus. Some studies with functional MRI reported that the
      stratum plays an important role in short-term memory and cognitive function. This
      case showed only a left putamen lesion, which indicates that a putamen lesion can
      cause transient global amnesia.

PMID- 27863872
TI  - Seasonal and temperature modifications of the association between fine
      particulate air pollution and cardiovascular hospitalization in New York state.
AB  - It is known that extreme temperature and ambient air pollution are each
      independently associated with human health outcomes. However, findings from the
      few studies that have examined modified effects by seasons and the interaction
      between air pollution and temperature on health endpoints are inconsistent. This
      study examines the effects of short-term PM2.5 (particulate matter less than or
      equal to 2.5MUm in aerodynamic diameter) on hospitalization for cardiovascular
      diseases (CVDs), its modifications by season and temperature, and whether these
      effects are heterogeneous across different regions in New York State (NYS). We
      used daily average temperature and PM2.5 concentrations as exposure indicators
      and performed a time series analysis with a quasi-Poisson model, controlling for
      possible confounders, such as time-relevant variables and dew point, for CVDs in
      NYS, 1991-2006. Stratification parametric models were applied to evaluate the
      modifying effects by seasons and temperature. Across the whole year, a 10-MUg/m3
      increment in PM2.5 concentration accounted for a 1.37% increase in CVDs (95%
      confidence interval (CI): 0.90%, 1.84%) in New York City, Long Island & Hudson.
      The PM2.5 effect was strongest in winter, with an additional 2.06% (95% CI:
      1.33%, 2.80%) increase in CVDs observed per 10-MUg/m3 increment in PM2.5.
      Temperature modified the PM2.5 effects on CVDs, and these modifications by
      temperature on PM2.5 effects on CVDs were found at low temperature days. These
      associations were heterogeneous across four PM2.5 concentration regions. PM2.5
      was positively associated with CVD hospitalizations. The short-term PM2.5 effect
      varied with season and temperature levels, and stronger effects were observed in
      winter and at low temperature days.

PMID- 27863874
TI  - Successful autologous haematopoietic stem cell transplantation for refractory
      myasthenia gravis - a case report.
AB  - Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against
      the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic
      treatment with choline esterase blockers, many patients also require
      immunomodulatory treatment. Despite existing treatment options, some patients are
      treatment refractory. We describe a patient with severe MG refractory to
      corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and
      bortezomib who was treated with autologous haematopoietic stem cell
      transplantation. Two years after this, the patient has significantly improved in
      objective tests and in quality of life and leads an active life. Diplopia is her
      only remaining symptom and she is completely free of medication for MG. We
      believe that autologous haematopoietic stem cell transplantation can be an
      effective therapeutic option for carefully selected cases of severe, treatment
      refractory MG.

PMID- 27863875
TI  - Knowledge of carrier status and barriers to testing among mothers of sons with
      Duchenne or Becker muscular dystrophy.
AB  - Our study objective was to survey female carriers for Duchenne and Becker
      muscular dystrophy to identify barriers to carrier testing and the impact of
      carrier risk knowledge on cardiac and reproductive health management. We surveyed
      women who have or had biological sons with Duchenne or Becker muscular dystrophy
      and were enrolled in the US DuchenneConnect patient registry, with questions
      assessing knowledge of carrier status and recurrence risk, knowledge of care
      standards for carriers, and barriers to testing. Of the 182 eligible respondents,
      25% did not know their carrier status and 14% incorrectly classified themselves
      as not at risk. Cost of testing was the most commonly identified barrier to
      testing. Women reporting unknown carrier status were 13 times as likely to
      express uncertainty regarding their recurrence risk compared to women reporting
      positive carrier status. 37% of women at an increased risk for cardiomyopathy had
      never had an echocardiogram. Women who were certain of their positive carrier
      status were twice as likely to have had an echocardiogram in the last five years
      compared to women with unknown carrier status. Future research on reducing
      barriers to counseling and carrier testing, such as cost, may improve care
      standard adherence.

PMID- 27863876
TI  - Scoping review: The use of early warning systems for the identification of in
      hospital patients at risk of deterioration.
AB  - INTRODUCTION: Early warning systems (EWS) were developed as a means of alerting
      medical staff to patient clinical decline. Since 85% of severe adverse events are
      preceded by abnormal physiological signs, the patient bed-side vital signs
      observation chart has emerged as an EWS tool to help staff identify and quantify
      deteriorating patients. There are three broad categories of patient observation
      chart EWS: single or multiple parameter systems; aggregated weighted scoring
      systems; or combinations of single or multiple parameter and aggregated weighted
      scoring systems. OBJECTIVE: This scoping review is an overview of quantitative
      studies and systematic reviews examining the efficiency of the adult EWS charts
      in the recognition of in-hospital patient deterioration. METHOD: A broad search
      was undertaken of peer-reviewed publications, official government websites and
      databases housing research theses, using combinations of keywords and phrases.
      DATA SOURCES: CINAHL with full text; MedLine, PsycINFO, MasterFILE Premier,
      GreenFILE and ScienceDirect. Also, the Cochrane Library database, Department of
      Health government websites and Ethos, ProQuest and Trove databases were searched.
      EXCLUSIONS: Paediatric, obstetric and intensive care studies, studies undertaken
      at the point of hospital admission or pre-admission, non-English publications and
      editorials. RESULTS: Five hundred and sixty five publications, government
      documents, reports and theses were located of which 91 were considered and 21
      were included in the scoping review. Of the 21 publications eight studies
      compared the efficacy of various EWS and 13 publications validated specific EWS.
      CONCLUSIONS: There is low level quantitative evidence that EWS improve patient
      outcomes and strong anecdotal evidence that they augment the ability of the
      clinical staff to recognise and respond to patient decline, thus reducing the
      incidence of severe adverse events. Although aggregated weighted scoring systems
      are most frequently used, the efficiency of the specific EWS appears to be
      dependent on the patient cohort, facilities available and staff training and
      attitude. While the review demonstrates support for EWS, researchers caution that
      given the contribution of human factors to the EWS decision-making process,
      patient EWS charts alone cannot replace good clinical judgment.

PMID- 27863877
TI  - Pro: Inhaled Pulmonary Vasodilators Should Be Used Routinely in the Management of
      Patients Undergoing Lung Transplantation.

PMID- 27863878
TI  - A Hazard of Transesophageal Echocardiography in a Neonate.

PMID- 27863879
TI  - Settling velocity of microplastic particles of regular shapes.
AB  - Terminal settling velocity of around 600 microplastic particles, ranging from 0.5
      to 5mm, of three regular shapes was measured in a series of sink experiments:
      Polycaprolactone (material density 1131kgm-3) spheres and short cylinders with
      equal dimensions, and long cylinders cut from fishing lines (1130-1168kgm-3) of
      different diameters (0.15-0.71mm). Settling velocities ranging from 5 to 127mms-1
      were compared with several semi-empirical predictions developed for natural
      sediments showing reasonable consistency with observations except for the case of
      long cylinders, for which the new approximation is proposed. The effect of
      particle's shape on its settling velocity is highlighted, indicating the need of
      further experiments with real marine microplastics of different shapes and the
      necessity of the development of reasonable parameterization of microplastics
      settling for proper modeling of their transport in the water column.

PMID- 27863880
TI  - Fractionation of heavy metals in sediments and assessment of their availability
      risk: A case study in the northwestern of Persian Gulf.
AB  - Sequential extraction procedure was applied to determine the chemical forms of
      heavy metals in sediments in order to assess their mobility and availability in
      the aquatic environment. The mean concentrations of Cr, Ni, Pb, Cd, Cu and Zn in
      exchangeable and carbonate fractions were 14.9, 30.9, 17, 0.37, 4.4 and
      14.4mg/kg, respectively. Based on the sediments quality guidelines (SQGs), the
      adverse biological effects caused by Ni, can occur frequently across the study
      area. Risk assessment code (RAC) suggested that the Cd has the highest level of
      environmental risk compared with other studied metals. Modified risk assessment
      code (mRAC) demonstrated a high potential adverse effect in the many of sampling
      sites. According to the fractionation results, the concentration of Ni in
      exchangeable and carbonate fractions was very considerable and more than other
      metals, hence, the potential risk of nickel release can be much more than other
      investigated metals.

PMID- 27863881
TI  - Isolation and characterization of a high-efficiency erythromycin A-degrading
      Ochrobactrum sp. strain.
AB  - In this work, Erythromycin A(EA)- degrading bacteria was isolated from the
      contaminated soil obtained from a pharmaceutical factory in China. The isolate
      designated as strain WX-J1 was identified as Ochrobactrum sp. by sequence
      analysis of its 16S rDNA gene. It can grow in a medium containing EA as the sole
      source of carbon and its optimal growth pH and temperature were 6.5 and 32
      degrees C, respectively. Under these conditions, when the initial Erythromycin A
      concentration was 100mg.L-1, 97% of Erythromycin A has been degraded. HPLC-MS
      analyses indicated that Erythromycin A degradation produced intermediates
      contained the following three substances: 3-depyranosyloxy erythromycin A, 7,12
      dyhydroxy-6-deoxyerythronolide B, 6-deoxyerythronolide B and propionaldehyde.
      Since Erythromycin A-degrading Ochrobactrum sp. strain rapidly degraded
      Erythromycin A, this strain might be useful for bioremediation purposes.

PMID- 27863882
TI  - Chemical composition of two mineralogically contrasting Arctic bivalves' shells
      and their relationships to environmental variables.
AB  - The main goal of this study was to determine the concentrations of trace elements
      in the mineralogically contrasting shells of two Arctic bivalves: Chlamys
      islandica and Ciliatocardium ciliatum. Aragonite shells seem to be more
      susceptible to the binding of metal ions, which is most likely a result of their
      crystal lattice structure. We suggest that less biologically controlled aragonite
      mineralization tends to incorporate more metal impurities into the crystal
      lattice in waters with a lower pH, where metal ions are more available. Higher
      concentrations of impurities may further increase the lattice distortion causing
      lower crystal lattice stability and higher susceptibility to dissolution.
      Calcitic shells seem to be less prone to bind metal ions than aragonite shells
      most likely because under strict biological control, the uptake of ions from
      ambient seawater is more selective; thus, the final crystal lattice is less
      contaminated by other metals and is more resistant to dissolution.

PMID- 27863883
TI  - Polymer/reduced graphene oxide functionalized sponges as superabsorbents for oil
      removal and recovery.
AB  - Polyurethane dish-washing (PU-DW) sponges are functionalized sequentially with
      polyethylenimine (PEI) and graphene oxide (GO) to form PEI/reduced graphene oxide
      (RGO) PU-DW sponges. The PEI/RGO PU-DW sponge consists of PEI/RGO sheets having
      numerous pores, with diameters ranging from 236 to 254nm. To further enhance
      hydrophobicity and absorption capacity of oil, PEI/RGO PU-DW sponge is further
      coated with 20% phenyltrimethoxysilane (PTMOS). The PTMOS/PEI/RGO PU-DW sponge
      absorbs various oils within 20s, with maximum absorption capacity values of 880%
      and 840% for bicycle chain oil and motorcycle engine oil, respectively. The
      absorbed oils were released completely by squeezing or immersed in hexane. The
      PTMOS/PEI/RGO PU-DW sponge efficiently separates oil/water mixtures through a
      flowing system. Having the advantages of faster absorption rate, reusability, and
      low cost, the PTMOS/PEI/RGO PU-DW sponge holds great potential as a
      superabsorbent for efficient removal and recovery of oil spills as well as for
      the separation of oil/water mixtures.

PMID- 27863884
TI  - Cultivation of activated sludge using sea mud as seed to treat industrial
      phenolic wastewater with high salinity.
AB  - A technique is proposed to treat saline hazardous wastewater by using marine
      activated sludge, cultivated with sea mud as seed. Since the developed marine
      activated sludge had phenol-tolerant microorganisms (MAS-1, MAS-2 and MAS-3)
      which originated from the ocean, it was envisaged that these bacteria could
      survive and breakdown phenol in saline environments. In this work, typical phenol
      tolerant microorganisms were isolated from the marine activated sludge and
      identified. After a hierarchical acclimation process, the marine activated sludge
      was used to treat the industrial phenolic wastewater with high salinity. The
      marine activated sludge was able to break down phenol and other organic
      components effectively and efficiently in treating the wastewater with salinity
      of 5.7% w/v. The results showed a high removal of phenol (99%), COD (80%) and NH3
      N (68%).

PMID- 27863885
TI  - Cell-type specific variation in the induction of ER stress and downstream events
      in chikungunya virus infection.
AB  - Over the last decade infections with the mosquito transmitted chikungunya virus
      (CHIKV) have become a major worldwide concern, and considerable efforts have been
      made in understanding the interaction of this virus with the host cell machinery.
      Studies have documented the induction of the unfolded protein response (UPR), as
      well as the induction of apoptosis and autophagy in response to CHIKV infection.
      This study comparatively analysed these three processes in two cell lines, Hela
      and HepG2. Infection of Hela cells was characterized by activation of the
      PERK/eIF2alpha branch of the UPR, the induction of autophagy and early apoptosis,
      while infection of HepG2 cells was characterized by activation of the IRE/XBP1
      branch of the UPR, limited or no activation of autophagy and comparatively later
      apoptosis. These results show that the specific cell context is an important
      mediator of the host cell response to CHIKV infection.

PMID- 27863886
TI  - Cognitive Control As a Double-Edged Sword.
AB  - Cognitive control, the ability to limit attention to goal-relevant information,
      aids performance on a wide range of laboratory tasks. However, there are many day
      to-day functions which require little to no control and others which even benefit
      from reduced control. We review behavioral and neuroimaging evidence
      demonstrating that reduced control can enhance the performance of both older and,
      under some circumstances, younger adults. Using healthy aging as a model, we
      demonstrate that decreased cognitive control benefits performance on tasks
      ranging from acquiring and using environmental information to generating creative
      solutions to problems. Cognitive control is thus a double-edged sword - aiding
      performance on some tasks when fully engaged, and many others when less engaged.

PMID- 27863888
TI  - Lipoma arborescens in bilateral knee joints accompany gouty tophi: A case-based
      review of the literature.

PMID- 27863887
TI  - Comfort and acceptability of various immobilization positions using a shoulder
      external rotation and abduction brace.
AB  - BACKGROUND: Immobilization with shoulder braces is used for conservative
      treatment of an initial shoulder dislocation. Various arm positions have been
      investigated to determine optimal position in terms of the anatomical reduction
      of the Bankart lesion. Recently, the effect of immobilization in shoulder
      abduction as well as in external rotation has been reported. However, there are
      few studies assessing subjects' acceptability of the brace in various arm
      positions. We hypothesized that a certain arm position regarding abduction or
      external rotation for immobilization would induce significant discomfort during
      activities of daily living. METHODS: A dominant arm of 20 healthy participants
      was immobilized with a shoulder brace in 4 different positions; adduction and
      internal rotation (Add-IR), adduction and external rotation (Add-ER), 30 degrees 
      of abduction and 30 degrees  of external rotation (Abd-30ER), and 30 degrees  of
      abduction and 60 degrees  of external rotation (Abd-60ER). After completing
      immobilization for 24 h, subjects were asked to assess the discomfort of bracing
      for overall and individual activities, using a visual analogue scale. Data were
      compared among the four positions. RESULTS: For overall activities and several
      activities (eating, reading books, and removing and putting on pants), Abd-60ER
      was significantly more uncomfortable than adducted arm positions. Abd-30ER did
      not show any differences compared to the other arm positions. CONCLUSION:
      Immobilization in abduction and external rotation seems to be acceptable although
      the arm position in 30 degrees  of abduction and 60 degrees  of external rotation
      is less comfortable than the others. Our results might be useful in determining
      and developing the ideal shoulder brace which could keep patients' compliance and
      improve their outcomes.

PMID- 27863889
TI  - Same-Day Discharge in Laparoscopic Acute Non-Perforated Appendectomy.
AB  - BACKGROUND: Small studies done during the past decade have demonstrated same-day
      discharge after appendectomy as an option for non-perforated appendicitis. Here
      we have examined a large cohort to confirm that same-day discharge in acute non
      perforated appendicitis is a safe option. STUDY DESIGN: This was a retrospective
      study of patients from 14 Southern California Region Kaiser Permanente medical
      centers. All patients older than 18 years of age with acute, non-perforated
      appendicitis who underwent a laparoscopic appendectomy between 2010 and 2014 were
      included. We compared patients discharged on the day of surgery with patients
      hospitalized for 1 night. We examined readmission rates, complication rates,
      postoperative emergency department visits, postoperative diagnostic or
      therapeutic radiology visits, reoperations, and cost of treatment. RESULTS: The
      cohort was composed of 12,703 patients; 6,710 patients were in the same-day
      discharge group and 5,993 patients were in the hospitalized group. Patients in
      the same-day discharge group had a lower rate of readmission within 30 days when
      compared with the hospitalized group (2.2% vs 3.1%; p < 0.005). In both groups,
      postoperative rates of visits to emergency or radiology department for diagnostic
      or therapeutic imaging studies were statistically similar. Postoperative general
      surgery department visits were slightly higher in the hospitalized group (85% vs
      81%; p < 0.001). CONCLUSIONS: Adult patients with acute, non-perforated
      appendicitis can be discharged safely on the day of surgery without higher rates
      of postoperative complication or readmission rates compared with those
      hospitalized after surgery. In addition, same-day discharge in this patient group
      is cost-effective.

PMID- 27863890
TI  - Normal values of cervical vertebral measurements according to age and sex in CT.
AB  - INTRODUCTION: Atlantodental interval (ADI), basion-dental interval (BDI) and the
      thickness of prevertebral soft tissue (TOPST) measured in lateral cervical
      radiographs were reported to be useful indicators and indirect signs of
      underlying cervical spine injuries. However, cervical computed tomography (MDCT)
      is the first method of imaging used in all trauma patients and upper normal
      limits (UNLs) of cervical distances according to age and sex are undetermined.
      Therefore, we aimed to calculate these metrics. METHODS: 500 adult trauma
      patients with cervical MDCT at the time of admission were retrospectively
      selected. ADI, BDI, and TOPSTs were measured by two blinded researchers. RESULTS:
      488 cervical spine CT scans were reported to be normal and 12 has pathological
      findings. Mean ADI, BDI and TOPST of C1, C2, C6 and C7 were statistically
      significantly wider in males. In females, ADI and BDI were significantly narrower
      with the increase in age. In males, only ADI was significantly narrower, and
      TOPST of C6 and C7 vertebra were significantly wider with the increase in age. We
      found the optimal UNLs as follows: ADI 2.5mm, BDI 8.5mm, C1 6.5mm, C2 5.7mm, C3
      6.3mm (6mm for C1-3 for practical purposes), C4 11.7 and C5-7 17mm. DISCUSSION:
      We believe that the increase in distances with age may be affected by the height
      losses of discs and vertebral bodies, formation of anterior osteophytes and
      regional kyphosis by age. Those results were compatible with the previous
      reports.

PMID- 27863891
TI  - Splenic rupture after emesis: A rare finding of generalized abdominal pain.

PMID- 27863893
TI  - Professor Carlo J. De Luca (1943-2016).

PMID- 27863892
TI  - Pericarditis mimicking Brugada syndrome.
AB  - INTRODUCTION: Brugada syndrome (BrS) is a genetic heart disorder due to
      alteration of the ion channels function that causes an impaired in the cardiac
      conduction system. It is characterized by an abnormal electrocardiogram pattern
      and may be complicated by malignant ventricular arrhythmias. Pericarditis is an
      inflammation of the pericardium and 90% of isolated cases of acute pericarditis
      are idiopathic or viral. Acute pericarditis may appears with chest pain, fever,
      pericardial friction rub, and cardiac tamponade. Moreover, widespread ST segment
      changes occur due to involvement of the underlying epicardium. CASE REPORT: A 27
      year-old man was admitted to the Emergency Department of the .... Hospital due to
      fatigue and chest discomfort. Laboratory findings showed that WBC count and C
      reactive protein were increased. Echocardiographic finding was normal. The
      patient was admitted with a diagnosis of pericarditis. Electrocardiogram (ECG)
      showed a "saddle back"-type ST elevation in leads V2, recognised as type 2
      Brugada pattern. The ECG normalized within a few days after the beginning of anti
      inflammatory therapy and the follow-up was uneventful. Based on findings in our
      patient and data from literature, we hypothesize that the patient developed a
      Brugada ECG pattern due the pericarditis. CONCLUSIONS: Our case report shows that
      the pericarditis may mimic BrS. Moreover, it is important to underline that a
      Brugada ECG pattern should only be considered as a sign of electrical heart
      disease but detailed diagnostic tests are anyway needed.

PMID- 27863894
TI  - Precise measurement of scleral radius using anterior eye profilometry.
AB  - PURPOSE: To develop a new and precise methodology to measure the scleral radius
      based on anterior eye surface. METHODS: Eye Surface Profiler (ESP, Eaglet-Eye,
      Netherlands) was used to acquire the anterior eye surface of 23 emmetropic
      subjects aged 28.1+/-6.6years (mean+/-standard deviation) ranging from 20 to 45.
      Scleral radius was obtained based on the approximation of the topographical
      scleral data to a sphere using least squares fitting and considering the axial
      length as a reference point. To better understand the role of scleral radius in
      ocular biometry, measurements of corneal radius, central corneal thickness,
      anterior chamber depth and white-to-white corneal diameter were acquired with
      IOLMaster 700 (Carl Zeiss Meditec AG, Jena, Germany). RESULTS: The estimated
      scleral radius (11.2+/-0.3mm) was shown to be highly precise with a coefficient
      of variation of 0.4%. A statistically significant correlation between axial
      length and scleral radius (R2=0.957, p<0.001) was observed. Moreover, corneal
      radius (R2=0.420, p<0.001), anterior chamber depth (R2=0.141, p=0.039) and white
      to-white corneal diameter (R2=0.146, p=0.036) have also shown statistically
      significant correlations with the scleral radius. Lastly, no correlation was
      observed comparing scleral radius to the central corneal thickness (R2=0.047,
      p=0.161). CONCLUSIONS: Three-dimensional topography of anterior eye acquired with
      Eye Surface Profiler together with a given estimate of the axial length, can be
      used to calculate the scleral radius with high precision.

PMID- 27863895
TI  - Paraoxonase 1 (Q192R) gene polymorphism, coronary heart disease and the risk of a
      new acute coronary event.
AB  - INTRODUCTION: Paraoxonase 1 (PON1) plays a major role in the oxidation of low
      density lipoprotein and in the prevention of coronary atherogenesis. In this
      context, coding region polymorphisms of PON1 gene, responsible for the enzyme
      activity, has become of interest as a marker for atherogenesis. METHODS: A study
      and follow-up was conducted on 529 patients with an acute coronary event in order
      to assess the association between the PON1 Q192R (rs662;A/G) polymorphism, the
      type of acute coronary syndrome, cardiovascular risk factors (arterial
      hypertension, diabetes mellitus, dyslipidaemia, and smoking), the extent and
      severity of coronary atherosclerosis, and the medium-term clinical follow-up.
      RESULTS: The QQ genotype was found in 245 (46.3%) patients, with 218 (41.2%)
      patients showing the QR genotype, and 66 (14.5%) patients had the RR genotype. No
      significant differences were found between the QQ and QR/RR genotypes as regards
      the clinical characteristics, the analytical data, and the angiographic
      variables. Similarly, Kaplan-Meier survival analysis showed no significant
      differences in presenting with a new acute coronary event (p=0.598), cardiac
      mortality (p=0.701), stent thrombosis (p=0.508), or stent re-stenosis (p=0.598)
      between QQ and QR/RR genotypes during the follow-up period (3.3+/-2.2 years).
      CONCLUSIONS: In patients with an acute coronary syndrome, the PON1 Q192R
      genotypes did not influence the risk of suffering a new acute coronary event
      during the medium-term follow-up.

PMID- 27863897
TI  - Fishing and the Radiologist.

PMID- 27863896
TI  - [Chronic kidney disease and dyslipidaemia].
AB  - Chronic kidney disease (CKD) has to be considered as a high, or even very high
      risk cardiovascular risk condition, since it leads to an increase in
      cardiovascular mortality that continues to increase as the disease progresses. An
      early diagnosis of CKD is required, together with an adequate identification of
      the risk factors, in order to slow down its progression to more severe states,
      prevent complications, and to delay, whenever possible, the need for renal
      replacement therapy. Dyslipidaemia is a factor of the progression of CKD that
      increases the risk in developing atherosclerosis and its complications. Its
      proper control contributes to reducing the elevated cardiovascular morbidity and
      mortality presented by these patients. In this review, an assessment is made of
      the lipid-lowering therapeutic measures required to achieve to recommended
      objectives, by adjusting the treatment to the progression of the disease and to
      the characteristics of the patient. In CKD, it seems that an early and intensive
      intervention of the dyslipidaemia is a priority before there is a significant
      decrease in kidney function. Treatment with statins has been shown to be safe and
      effective in decreasing LDL-Cholesterol, and in the reduction of cardiovascular
      events in individuals with CKD, or after renal transplant, although there is less
      evidence in the case of dialysed patients.

PMID- 27863898
TI  - Automated 3D Rendering of Ribs in 110 Polytrauma Patients: Strengths and
      Limitations.
AB  - RATIONALE AND OBJECTIVES: To evaluate the strengths and limitations of a rib
      unfolding software in a polytrauma context. MATERIALS AND METHODS: Chest computed
      tomography (CT) examinations of 110 patients were reviewed for specific detection
      of rib fractures using: (1) transverse CT sections +/-  multiplanar reformattings
      (ie, the standard of reference), and (2) unfolded rib images reconstructed by the
      CT Bone Reading software with the possibility of rib analysis along their long
      axis and creation of standard orthogonal views in different orientations of any
      area suspected of fracture. RESULTS: The software provided complete
      reconstruction of the whole rib cage in 94 patients (85.5%) and partially
      incomplete reconstruction in 16 patients (14.5%). The percentage of ribs
      inadequately reconstructed was 1.5% (40 of 2640 ribs), mainly related to unfused
      epiphyses (13 of 40), costal hypoplasia (8 of 40), and vertebral fracture (6 of
      40). The sensitivity and specificity in detecting rib fractures at a per-patient,
      per-rib, and per-costal arc level ranged from 0.73 to 0.84 and 0.99 to 1,
      respectively. At a costal arc level, the reader's misinterpretations accounted
      for 67% (4 of 6) of false-positive and 24% (20/84) of false-negative results, and
      interpretive difficulties were encountered for single-cortex fractures or
      fractures at the extremities of the costal shaft. CONCLUSIONS: An accurate
      diagnosis of rib fracture was achieved with the reading of unfolded rib images.
      In a polytrauma context, the evaluated system could facilitate rib analysis.

PMID- 27863899
TI  - CT Angiography: Post-processed Contrast Enhancement for Improved Detection of
      Pulmonary Embolism.
AB  - RATIONALE AND OBJECTIVES: The study aimed to improve the detection of pulmonary
      embolism via an iodine contrast enhancement tool in patients who underwent
      suboptimal enhanced computed tomography angiography (CTA). MATERIALS AND METHODS:
      We evaluated the CT examinations of 41 patients who underwent CTA for evaluation
      of the pulmonary arteries which suffered from suboptimal contrast enhancement.
      The contrast enhancement of the reconstructed images was increased via a post
      processing tool (vContrast). Image noise and contrast-to-noise ratio (CNR) were
      assessed in eight different regions: main pulmonary artery, right and left
      pulmonary arteries, right and left segment arteries, muscle, subcutaneous fat,
      and bone. For subjective image assessment, three experienced radiologists
      evaluated the diagnostic quality. RESULTS: While employing the post-processing
      algorithm, the CNR for contrast-filled lumen and thrombus/muscle improves
      significantly by a factor of 1.7 (CNR without vContrast = 8.48 +/- 6.79/CNR with
      vContrast = 14.46 +/- 5.29) (P <0.01). No strengthening of artifacts occurred,
      and the mean Hounsfield unit values of the muscle, subcutaneous fat, and the bone
      showed no significant changes. Subjective image analysis illustrated a
      significant improvement using post-processing for clinically relevant criteria
      such as diagnostic confidence. CONCLUSIONS: vContrast makes CT angiograms with
      inadequate contrast applicable for diagnostic evaluation, offering an improved
      visualization of the pulmonary arteries. In addition, vContrast can help in the
      significant reduction of the iodine contrast material.

PMID- 27863900
TI  - Introduction to special issue.

PMID- 27863902
TI  - Prediction and Prevention of Parasitic Diseases Using a Landscape Genomics
      Framework.
AB  - Substantial heterogeneity exists in the dispersal, distribution and transmission
      of parasitic species. Understanding and predicting how such features are governed
      by the ecological variation of landscape they inhabit is the central goal of
      spatial epidemiology. Genetic data can further inform functional connectivity
      among parasite, host and vector populations in a landscape. Gene flow correlates
      with the spread of epidemiologically relevant phenotypes among parasite and
      vector populations (e.g., virulence, drug and pesticide resistance), as well as
      invasion and re-invasion risk where parasite transmission is absent due to
      current or past intervention measures. However, the formal integration of spatial
      and genetic data ('landscape genetics') is scarcely ever applied to parasites.
      Here, we discuss the specific challenges and practical prospects for the use of
      landscape genetics and genomics to understand the biology and control of
      parasitic disease and present a practical framework for doing so.

PMID- 27863903
TI  - TrypTag.org: A Trypanosome Genome-wide Protein Localisation Resource.

PMID- 27863904
TI  - Exacerbating factors of itch in atopic dermatitis.
AB  - Atopic dermatitis (AD) displays different clinical symptoms, progress, and
      response to treatment during early infancy and after childhood. After the
      childhood period, itch appears first, followed by formation of well-circumscribed
      plaque or polymorphous dermatoses at the same site. When accompanied with
      dermatitis and dry skin, treatment of skin lesions should be prioritized. When
      itch appears first, disease history, such as causes and time of appearance of
      itch should be obtained by history taking. In many cases, itch increases in the
      evening when the sympathetic nerve activity decreased. Treatment is provided
      considering that hypersensitivity to various external stimulations can cause
      itch. Heat and sweating are thought to especially exacerbate itch. Factors
      causing itch, such as cytokines and chemical messengers, also induce itch mainly
      by stimulating the nerve. Scratching further aggravates dermatitis. Skin
      hypersensibility, where other non-itch senses, such as pain and heat, are felt as
      itch, sometimes occurs in AD. Abnormal elongation of the sensory nerve into the
      epidermis, as well as sensitizing of the peripheral/central nerve, are possible
      causes of hypersensitivity, leading to itch. To control itch induced by
      environmental factors such as heat, treatment for dermatitis is given priority.
      In the background of itch exacerbated by sweating, attention should be given to
      the negative impact of sweat on skin homeostasis due to 1) leaving excess sweat
      on the skin, and 2) heat retention due to insufficient sweating. Excess sweat on
      the skin should be properly wiped off, and dermatitis should be controlled so
      that appropriate amount of sweat can be produced. Not only stimulation from the
      skin surface, but also visual and auditory stimulation can induce new itch. This
      "contagious itch" can be notably observed in patients with AD. This article
      reviews and introduces causes of aggravation of itch and information regarding
      how to cope with such causes.

PMID- 27863905
TI  - Eyes in the Chameleon Vine?

PMID- 27863907
TI  - Evidence of epigenetic tags in cardiac fibrosis.
AB  - In cardiac fibrosis, following an injury or a stress, non-functional fibrotic
      tissue substitutes normal myocardium, thus leading to progressive heart failure.
      Activated fibroblasts are principal determinants of cardiac fibrosis by producing
      excessive fibrotic extracellular matrix and causing hypertrophy of
      cardiomyocytes. Epigenetic changes, such as DNA methylation, histone
      modifications, and miRNAs have been involved in these mechanisms. Therefore,
      there is a strong interest in reverting such epigenetic transformations in order
      to arrest myocardial fibrotic degeneration. Demethylating agents, such as 5-aza
      2'-deoxycytidine, 5-azacytidine, some selective histone deacetylase inhibitors,
      including mocetinostat, trichostatin A, and MPT0E014, have a direct action on
      important inducers of cardiac fibrosis. Also dietary compounds, such as
      resveratrol, can suppress the differentiation of fibroblasts to myofibroblasts.
      Although in vivo and in vitro studies suggest specific epigenetic therapies to
      treat cardiac fibrosis, the related clinical trials are still lacking. A better
      understanding of the epigenetic effects of dietary compounds (e.g. curcumin and
      green tea catechins) on the onset and progression of cardiac fibrosis, will allow
      the identification of protective dietary patterns and/or the generation of novel
      potential epidrugs.

PMID- 27863906
TI  - Post-translational Control of Intracellular Pathogen Sensing Pathways.
AB  - Mammalian cells recognize virus-derived nucleic acids using a defined set of
      intracellular sensors including the DNA sensors cyclic GMP-AMP (cGAMP) synthase
      (cGAS) and interferon gamma (IFNgamma)-inducible protein 16 (IFI16) as well as
      viral RNA receptors of the retinoic acid-inducible gene I (RIG-I)-like receptor
      (RLR) family. Following innate immune recognition, these sensors launch an immune
      response that is characterized by the transcriptional upregulation of many
      antiviral molecules, including proinflammatory cytokines, chemokines, and IFN
      stimulated genes. Recent studies have demonstrated that the signal transduction
      initiated by these sensors is sophisticatedly regulated by post-translational
      modifications (PTMs) resulting in a robust yet 'tunable' cytokine response to
      maintain immune homeostasis. Here we summarize recent advances in our
      understanding of how PTMs and regulatory enzymes control the signaling activity
      of RLRs, cGAS, and IFI16 as well as their proximal adaptor proteins.

PMID- 27863908
TI  - Role of echocardiography for catheter-based management of valvular heart disease.
AB  - Catheter-based treatment of valvular heart disease, such as transvalvular aortic
      valve replacement (TAVR) or mitral clip procedure, has been increasingly accepted
      as a treatment choice for the past several years. Such new treatment options have
      been changing the management of patients with valvular heart disease drastically
      while socio-economic factors regarding their application need to be taken into
      consideration. The use of echocardiography, including transesophageal
      echocardiography (TEE), for such catheter-based treatments is essential for the
      success of the procedures. Severe hypotension after TAVR is a life-threatening
      emergency. Rapid assessment and diagnosis in the catheterization or hybrid
      laboratory is essential for safety and a positive outcome. Possible diagnoses in
      this critical situation would include severe left ventricular dysfunction due to
      coronary obstruction, cardiac tamponade, aortic rupture, acute severe aortic
      and/or mitral valve regurgitation, and hypovolemia due to bleeding. Although new
      types of TAVR valves reduce para-valvular aortic regurgitation (AR)
      significantly, it is still important to judge the severity of para-valvular AR
      correctly in the laboratory. As for mitral clip procedure, TEE is vital for
      guiding and monitoring the entire process. Accurate identification of the
      location and the geometry of the regurgitant orifice is necessary for proper
      placement of the clip. Real-time 3D TEE provides helpful en face view of the
      mitral valve and clip together to this end. Residual mitral regurgitation (MR)
      after the first clip is not uncommon. Quick and precise imaging of the residual
      MR (location and severity) with TEE is extremely important for the
      interventionist to place the second clip and possibly third clip properly. After
      the completion of the clip procedure, mitral valve stenosis and also iatrogenic
      atrial septal defect need to be checked by TEE. Echocardiography, especially TEE,
      is also vital for the success of other newer trans-catheter procedures such as
      device closure of para-valvular MR of the artificial valve, valve in valve
      procedure, and native valve replacement.

PMID- 27863909
TI  - Low frequency of toothbrushing practices is an independent risk factor for
      diabetes mellitus in male and dyslipidemia in female: A large-scale, 5-year
      cohort study in Japan.
AB  - BACKGROUND: We previously reported the association between toothbrushing
      practices and diabetes mellitus (DM) and dyslipidemia (DL) in a cross-sectional
      study. This study was conducted to clarify whether low frequency of toothbrushing
      practices is an independent risk factor for DM and DL using a follow-up design.
      METHODS: This study was a 5-year retrospective cohort study at St. Luke's
      International Hospital, Tokyo, Japan. We analyzed study subjects between 30 and
      85 years old in 2004, who underwent annual medical examination both in 2004 and
      2009. We compared the cumulative incidences of developing DM, DL, hypertension
      (HT), and hyperuricemia (HUA) between 2004 and 2009 among 3 groups: toothbrushing
      practices 'after every meal,' 'at least once a day,' and 'less than once a day'.
      Furthermore, we analyzed odds ratios (ORs) of risk for developing DM and DL by
      sex after making adjustments for age, obesity, DM, DL, HT, and HUA between two
      groups: 'after every meal' and 'not after every meal.' RESULTS: The number of
      study subjects was 13,070. Of 13,070 study subjects, 575 had DM, 5118 had DL,
      2599 had HT, and 1908 had HUA in 2004. We excluded the subjects with each disease
      in 2004. The cumulative incidences (rates) of DM, DL, HT, and HUA between 2004
      and 2009 were 318 (2.5%), 1454 (18.3%), 1108 (10.6%), and 489 (4.4%),
      respectively. Toothbrushing practices 'not after every meal' was a significant
      risk factor for developing DM in male [OR: 1.43; 95% confidence interval (CI),
      1.040-1.970] and developing DL in female (OR: 1.18; 95% CI, 1.004-1.383) compared
      with toothbrushing practices 'after every meal.' CONCLUSION: Toothbrushing
      practices 'after every meal' prevented developing DM in males and DL in females
      significantly. Toothbrushing practices may be beneficial to reduce developing
      risk factors for cardiovascular disease.

PMID- 27863901
TI  - A systematic review of the literature on disorders of sleep and wakefulness in
      Parkinson's disease from 2005 to 2015.
AB  - Sleep disorders are among the most common non-motor manifestations in Parkinson's
      disease (PD) and have a significant negative impact on quality of life. While
      sleep disorders in PD share most characteristics with those that occur in the
      general population, there are several considerations specific to this patient
      population regarding diagnosis, management, and implications. The available
      research on these disorders is expanding rapidly, but many questions remain
      unanswered. We thus conducted a systematic review of the literature published
      from 2005 to 2015 on the following disorders of sleep and wakefulness in PD: REM
      sleep behavior disorder, insomnia, nocturia, restless legs syndrome and periodic
      limb movements, sleep disordered breathing, excessive daytime sleepiness, and
      circadian rhythm disorders. We discuss the epidemiology, etiology, clinical
      implications, associated features, evaluation measures, and management of these
      disorders. The influence on sleep of medications used in the treatment of motor
      and non-motor symptoms of PD is detailed. Additionally, we suggest areas in need
      of further research.

PMID- 27863910
TI  - Gabor frames for classification of paroxysmal and persistent atrial fibrillation
      episodes.
AB  - In this study, we propose a new classification method for early differentiation
      of paroxysmal and persistent atrial fibrillation episodes, i.e. those which
      spontaneously or with external intervention will return to sinus rhythm within 7
      days of onset from the ones where the arrhythmia is sustained for more than 7
      days. Today, clinicians provide patients classification once the course of the
      arrhythmia has been disclosed. This classification problem is dealt with in this
      study. We study a sparse representation of surface electrocardiogram signals by
      means of Gabor frames and afterwards we apply a linear discriminant analysis.
      Thus, we provide an early discrimination, obtaining promising performances on a
      heterogeneous cohort of patients in terms of pharmacological treatment and state
      of progression of the arrhythmia: 95% sensitivity, 82% specificity, 89% accuracy.
      In this manner, the proposed method can help clinicians to choose the most
      appropriate treatment using the electrocardiogram, which is a widely available
      and non-invasive technique. This early differentiation is clinically highly
      significant in order to choose optimal patients who may undergo catheter ablation
      with higher success rates.

PMID- 27863911
TI  - Crizotinib for ROS1 patients: One small step in biomarker testing, one giant leap
      for advanced NSCLC patients.

PMID- 27863912
TI  - Concerns About the "Methods" Sections of Reviewed Papers.

PMID- 27863913
TI  - Commentary on "Randomised Controlled Trial: Potential Benefit of a Footplate
      Neuromuscular Electrical Stimulation Device in Patients with Chronic Venous
      Disease".

PMID- 27863914
TI  - Cultural aspects and mythologies surrounding menstruation and abnormal uterine
      bleeding.
AB  - The objective of this chapter is to present an overview of how menstruation, a
      normal bodily function, was and is perceived in various ethnic groups and
      cultures in the world, from ancient mythology, historical, or traditional
      practices to contemporary belief systems. Mythical tales about menstruation
      abound in the legends and prehistory of ancient cultures. These tales
      characterize menstrual blood variously as sacred, a gift from the gods, or a
      punishment for sin, but it is almost always magical and powerful. In contrast,
      most world religions view menstruation, with varying degrees of severity, as a
      major problem, a sign of impurity and uncleanliness, and therefore, menstruating
      women are isolated, prohibited from polluting the holy places, and shunned. Many
      of these myths and cultural misperceptions persist to the present day, reflected
      in a wide range of negative attitudes toward menstruation, which can have serious
      and direct implications for reproductive health. In view of the increasingly
      globalized nature of current clinical practice, it is crucial that health care
      providers are familiar with existing cultural and social views and attitudes
      toward the menstrual function. The ultimate goal is to be able to provide women
      culturally sensitive and medically appropriate therapies for their menstrual
      disorders. This biocultural approach to menstruation management is desirable in
      contemporary medical practice.

PMID- 27863915
TI  - Prenatal ultrasound monitoring of homozygous alpha0-thalassemia-induced fetal
      anemia.
AB  - A noninvasive approach by serial ultrasound examination at 12-15, 18, and 30
      weeks of gestation can be used to exclude homozygous alpha0-thalassemia-induced
      fetal anemia. At 12-15 weeks of gestation, the predictive values for the fetal
      cardio-thoracic ratio were better than that for the placental thickness. At 16-20
      weeks of gestation, measuring middle cerebral artery peak systolic velocity is
      associated with a low false-positive rate. However, the false-positive rate of
      this noninvasive approach can be about 3%, requiring an invasive test to confirm
      the diagnosis. A false-negative may result in a delay in diagnosis. The success
      of this noninvasive approach depends on an accurate measurement of the fetal
      cardiothoracic ratio which can be improved by adequate training and subsequent
      quality control. Currently, there is a lack of data reporting the performance of
      a noninvasive approach before 12 weeks of gestation.

PMID- 27863916
TI  - Structure-activity relationship study towards non-peptidic positron emission
      tomography (PET) radiotracer for gastrin releasing peptide receptors: Development
      of [18F] (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy)pyridin-2
      yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamide.
AB  - Gastrin-releasing peptide receptors (GRP-Rs, also known as bombesin 2 receptors)
      are overexpressed in a variety of human cancers, including prostate cancer, and
      therefore they represent a promising target for in vivo imaging of tumors using
      positron emission tomography (PET). Structural modifications of the non-peptidic
      GRP-R antagonist PD-176252 ((S)-1a) led to the identification of the fluorinated
      analog (S)-3-(1H-indol-3-yl)-N-[1-[5-(2-fluoroethoxy)pyridin-2
      yl]cyclohexylmethyl]-2-methyl-2-[3-(4-nitrophenyl)ureido]propionamide ((S)-1m)
      that showed high affinity and antagonistic properties for GRP-R. This antagonist
      was stable in rat plasma and towards microsomal oxidative metabolism in vitro.
      (S)-1m was successfully radiolabeled with fluorine-18 through a conventional
      radiochemistry procedure. [18F](S)-1m showed high affinity and displaceable
      interaction for GRP-Rs in PC3 cells in vitro.

PMID- 27863917
TI  - Pelvic fracture in multiple trauma: A 67-case series.
AB  - INTRODUCTION: Severe pelvic trauma remains associated with elevated mortality,
      largely due to hemorrhagic shock. OBJECTIVE: The main study objective was to test
      for correlation between fracture type and mortality. The secondary objective was
      to assess the efficacy in terms of mortality of multidisciplinary management
      following a decision-tree in multiple trauma victims admitted to a level 1 trauma
      center. MATERIAL AND METHODS: Between July 2011 and July 2013, 534 severe trauma
      patients were included in a single-center continuous prospective observational
      study. All patients with hemorrhagic shock received early treatment by pelvic
      binder. Patients with active bleeding on full-body CT or persisting hemorrhagic
      shock underwent arteriography with or without embolization. Pelvic trauma was
      graded on the Tile classification. The principle end-point was mortality.
      RESULTS: Median age was 40 years (range, 26-48 years), with a 79% male/female sex
      ratio. Thirty-two of the 67 patients with pelvic trauma (48%) were in hemorrhagic
      shock at admission. Median injury severity score (ISS) was 36 (range, 24-43). On
      the Tile classification, 22 patients (33%) were grade A, 33 (49%) grade B and 12
      (18%) grade C. Overall mortality was 19%, and 42% in case of hemorrhagic shock.
      Mortality was significantly higher with Tile C than A or B (58% vs. 9.1% and
      12.1%, respectively; P=0.001). CONCLUSION: Vertical shear fracture (Tile C) was
      associated with greater mortality from hemorrhagic shock. LEVEL OF EVIDENCE: IV,
      case series.

PMID- 27863918
TI  - Discontinuation of Plavix(r) (clopidogrel) for hip fracture surgery. A systematic
      review of the literature.
AB  - : The elderly population is increasing worldwide, associated with an increase in
      diseases related to aging, such as hip fractures. These patients are sometimes
      treated with clopidogrel. There are no arguments at present to clearly determine
      the risk/benefit ratio of early surgical management of traumatic hip fractures in
      patients treated with clopidogrel (perioperative blood loss, postoperative
      complications). The goal of this systematic review of the literature was to show
      that early surgical management (<48h) of patients treated with clopidogrel does
      not increase postoperative morbidity or mortality. Systematic review of the
      literature: level of evidence IV. A bibliographic search was performed in July
      2015 in PubMed, Embase and Cochrane databases using the MeSh keywords
      "Clopidogrel or Plavix(r)" AND "hip fracture". Two of the authors analyzed 48
      articles based on the title and abstract. Twenty-one articles were selected and
      read completely with an analysis of the references. Nine articles were chosen.
      Early surgical management (<48h) of patients receiving clopidogrel did not
      increase mortality at 30days, 3months or 1 year (between 25 and 30% mortality at
      1 year) and did not result in an increase in perioperative bleeding. The
      risk/benefit ratio of early surgical management of patients with hip fractures
      receiving clopidogrel is good; morbidity and mortality are not increased in these
      patients if surgery is performed immediately or less than 48h after admission.
      LEVEL OF EVIDENCE: IV.

PMID- 27863919
TI  - Direct lateral vs posterolateral approach to hemiarthroplasty for femoral neck
      fractures.
AB  - INTRODUCTION: Adopting the direct lateral (DL) instead of the posterolateral (PL)
      approach in hip arthroplasty for femoral neck fracture (FNF) patients could lower
      the rate of prosthetic dislocation. However, little is known about how the
      approach influences the functional outcome. HYPOTHESIS: We hypothesized that both
      approaches would give comparable results. MATERIAL AND METHODS: In a prospective
      cohort study, we enrolled 185 hips (183 patients, 128 women, median age 84 years)
      with a displaced FNF. Subjects were assigned to treatment using DL (n=102) or PL
      approach (n=83) with a hemiarthroplasty (HA). Functional outcome was assessed by
      Harris Hip Score (HHS), Western Ontario and McMaster Universities Arthritis
      (WOMAC) index, pain numeric rating scale (PNRS) for pain, mortality and hip
      complications. Patients were followed-up after 1 year. RESULTS: The HHS was 71
      (SD 18) in the DL group and 72 (SD 17) in the PL group (P=0.59). We found no
      difference in WOMAC, PNRS and mortality. Seven patients (6.9%) in the DL group
      and 11 patients (13.3%) in the PL group had undergone a major reoperation
      (adjusted OR 0.51; 95% CI, 0.18-2.07; P=0.23). DISCUSSION: In this prospective
      cohort study, patients treated with HA for FNF using either the DL or PL
      approaches had comparable functional outcome after 1 year. The PL approach had a
      tendency towards a higher reoperation rate. TYPE OF STUDY: Prospective cohort
      study. LEVEL OF PROOF: Level 2.

PMID- 27863920
TI  - Haplotype data for 17 Y-STR loci in the population of Madhya Pradesh, India.

PMID- 27863921
TI  - Unhealthy Weight Management Practices and Non-medical Use of Prescription Drugs.
AB  - INTRODUCTION: Non-medical use of prescription drugs (NMUPD) has reached epidemic
      proportions in the U.S. With approximately one in five high school students
      engaging in NMUPD, it is important to understand behavioral correlates. METHODS:
      Data were combined from the 2011 and 2013 cycles of the Youth Risk Behavior
      Survey, a nationally representative, cross-sectional survey. After restricting
      the analytic sample to students who reported a weight loss goal of either staying
      the same weight or losing weight, logistic regression models were used to
      estimate adjusted prevalence ratios and 95% CIs for associations between
      unhealthy weight management practices (UWMPs) and lifetime NMUPD. Individual
      UWMPs-fasting; taking diet pills, powders, or liquids without a doctor's advice;
      and vomiting or taking laxatives-and total number of UWMPs were examined. Data
      were analyzed in 2016. RESULTS: UWMPs were more prevalent among female students
      (21.1% vs 10.7% for fasting; 7.5% vs 5.2% for taking diet pills, powders, or
      liquids; and 7.6% vs 3.2% for vomiting or taking laxatives). Significant
      associations between individual UWMPs and NMUPD and between the number of UWMPs
      and NMUPD were observed. DISCUSSION: UWMPs were associated with NMUPD. Health
      educators in the school setting, as well as other health professionals who
      provide services to an adolescent population, can focus on healthy weight
      management strategies, and other substance-specific messages. CONCLUSIONS: The
      association between UWMPs and NMUPD may reflect a constellation of problem
      behaviors exhibited among some adolescents.

PMID- 27863922
TI  - Dual energy CT to reveal pseudo leakage of frozen elephant trunk.

PMID- 27863923
TI  - Pretreatment Red Blood Cell Total Folate Concentration Is Associated With
      Response to Pemetrexed in Stage IV Nonsquamous Non-Small-cell Lung Cancer.
AB  - INTRODUCTION: Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine
      and purine synthesis. Previous studies of genetic variation in these enzymes as
      predictors of pemetrexed efficacy have yielded inconsistent results. We
      investigated whether red blood cell (RBC) total folate, a phenotypic rather than
      genotypic, marker of cellular folate status was associated with the response to
      pemetrexed-based chemotherapy in advanced nonsquamous non-small-cell lung cancer
      (NSCLC). MATERIALS AND METHODS: We conducted a prospective cohort study of
      patients with stage IV nonsquamous NSCLC receiving first-line chemotherapy
      containing pemetrexed. The pretreatment RBC total folate level was quantified
      using liquid chromatography mass spectrometry. We then compared the objective
      response rate (ORR) between patients with RBC total folate concentrations greater
      than and less than an optimal cutoff value determined from the receiver operating
      characteristic curve. A logistic regression model was used to adjust for age,
      sex, and the use of bevacizumab. RESULTS: The ORR was 62% (32 of 52 patients).
      Receiver operating characteristic analysis was used to establish that a RBC total
      folate cutoff value of 364.6 nM optimally discriminated between pemetrexed
      responders and nonresponders. Patients with RBC total folate < 364.5 nM had an
      ORR of 27% compared with 71% for patients with RBC total folate > 364.5 nM (P =
      .01). This difference persisted after adjusting for age, sex, and the use of
      bevacizumab (odds ratio, 0.07; 95% confidence interval, 0.01-0.57; P = .01).
      CONCLUSION: A low pretreatment RBC total folate was associated with an inferior
      response to pemetrexed-based chemotherapy in stage IV nonsquamous NSCLC. Larger,
      multicenter studies are needed to validate RBC total folate as a predictive
      marker of pemetrexed response.

PMID- 27863924
TI  - Successful Use of Afatinib After Erlotinib-induced Pneumonitis in a Patient With
      Epidermal Growth Factor Receptor-mutant Lung Cancer.

PMID- 27863925
TI  - Number and function of circulating endothelial progenitor cells in patients with
      primary Budd-Chiari syndrome.
AB  - BACKGROUND AND AIM: Primary Budd-Chiari syndrome (BCS) is associated with
      vascular endothelial injury. Circulating endothelial progenitor cells (EPCs)
      provide an endogenous mechanism to repair endothelial injury. This study
      investigated the levels and functionality of EPCs in patients with primary BCS.
      METHODS: EPCs (CD34+/CD133+/KDR+) were quantified in 82 patients with primary BCS
      (inferior vena cava type: n=19; hepatic vein type: n=22; and mixed type: n=41),
      10 cirrhosis controls (CC group) and 10 age-matched healthy controls (HC group),
      using flow cytometry. EPCs proliferation was detected by MTT assay, adhesion by
      adhesion activity assay, and migration capacity by Transwell assay. RESULTS: EPCs
      levels were significantly lower in the BCS group (0.020+/-0.005%) than in the CC
      and HC groups (0.260+/-0.201%, 0.038+/-0.007%; P<0.001 for each). EPCs cultured
      in vitro from BCS and CC groups had, respectively, lower proliferation activity
      (0.20+/-0.04, 0.23+/-0.06 vs 0.58+/-0.07, each P<0.001), adhesion activity
      (15.8+/-1.7, 18.2+/-4.3 vs 35.0+/-2.5 cells/random microscopic field (RMF), each
      P<0.001) and migration activity (16.1+/-1.5, 16.7+/-3.0 vs 23.9+/-2.0 cells/RMF,
      each P<0.001) than in the HC group. EPCs functionality did not significantly
      differ between the BCS and CC groups. The numbers and functions of EPCs did not
      significantly differ among patients with inferior vena cava type, hepatic vein
      type and mixed type of BCS. CONCLUSION: Patients with primary BCS had lower EPCs
      levels, with less proliferation, adhesion and migration activities. These
      findings suggest that lower levels of less functional EPCs may be associated with
      venous occlusion in primary BCS patients.

PMID- 27863926
TI  - Combination of temsirolimus and adriamycin exhibits an enhanced antitumor effect
      in hepatocellular carcinoma.
AB  - OBJECTIVE: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in
      hepatocellular carcinoma (HCC). The aim of this study is to investigate the anti
      HCC effect of combination of temsirolimus, an mTOR inhibitor, and adriamycin, a
      routinely used drug for treating HCC. METHODS AND MATERIALS: Proliferation of HCC
      cells exposure to temsirolimus, adriamycin, and their combination was determined
      using MTT assay in vitro as well as in a nude mice model in vivo. Cell apoptosis
      was examined using flow cytometry. Expressions of apoptosis-related proteins
      including caspase-9, -3, PARP, Bax, and Bcl-2 were determined using Western
      blotting. RESULTS: Temsirolimus plus adriamycin showed an enhanced inhibitory
      effect on cell proliferation compared to temsirolimus or adriamycin in HCC cells
      PLC/PRF/5, BEL7402, and HuH7 in vitro. The drug combination solicited a higher
      percentage of apoptosis cells and induced higher levels of cleaved caspase-9, -3,
      and PARP than temsirolimus or adriamycin used alone. The ratio of Bax/Bcl-2 was
      increased in cells exposed to the combination treatment. The enhanced anti-tumor
      effect of this drug combination was verified in a nude mice model. We also
      observed that half doses of temsirolimus and adriamycin used in combination
      achieved a comparable tumor growth inhibitor rate with full dose of temsirolimus
      or adriamycin used alone. CONCLUSION: Temsirolimus plus adriamycin exhibited an
      enhanced antitumor effect in HCC and this drug combination might have a potential
      value in treatment of HCC. Studies are warranted to comprehensively evaluate the
      efficacy and safety of this regimen in the future.

PMID- 27863927
TI  - Concomitant injury of the annular ligament in fractures of the coronoid process
      and the supinator crest.
AB  - BACKGROUND: Fractures of the coronoid process or the supinator crest, as well as
      arthroscopic resection of osteophytes around the coronoid process, can endanger
      the attachment of the annular ligament (AL) to the proximal ulna. The purpose of
      this study was to investigate the corresponding insertional areas of the AL
      within this context. METHODS: In 30 embalmed human cadaveric elbow specimens, the
      insertional area of the AL at the anterior and posterior margin of the sigmoid
      notch was characterized. The distances and relations of the AL insertion
      anteriorly to the coronoid surface, the coronoid tip, and the depth of the
      coronoid process, as well as posteriorly to the supinator crest, were evaluated
      macroscopically. RESULTS: The mean distance of the anterior insertion area was
      1.9 +/- 0.6 mm (range, 1.0-3.1 mm) to the coronoid articular surface and 6.2 +/-
      1.7 mm (range, 2.9-10.2 mm) to the tip of the coronoid. The distance of the
      anterior insertion in relation to the depth of the coronoid process was 44% +/-
      11% (range, 30%-69%). The distance of the posterior insertion area to the level
      of the sigmoid notch measured from 3.5 +/- 1.5 mm (range, 0.5-6.5 mm) to 17.7 +/-
      2.9 mm (range, 13.1-25.4 mm). CONCLUSIONS: Coronoid fractures involving 44% or
      more of the coronoid process and anterolaterally oriented fractures where one
      third of the anterolateral facet is affected are accompanied by a complete
      anterior bony disruption of the AL. Arthroscopic resection of the coronoid tip
      should be limited to 1 mm distal to the coronoid articular surface to avoid
      injury to the AL. Fractures of the upper half of the supinator crest place the AL
      at risk at its posterior insertion.

PMID- 27863928
TI  - A scoping review of the role of LEGO(r) therapy for improving inclusion and
      social skills among children and youth with autism.
AB  - BACKGROUND: LEGO(r) therapy uses children's natural interest in play to help
      motivate behavioural change and may be an effective teaching tool to increase
      social competency and communication skills. Although the literature is growing it
      has not been synthesized. OBJECTIVES: To review the literature on the role of
      LEGO(r) therapy on social skills and inclusion among children and youth with
      Autism Spectrum Disorder (ASD). METHODS: A scoping review was conducted,
      involving comprehensive searches of international databases. Eligible articles
      included: (a) youth aged 19 or younger, with ASD; (b) empirical research on
      LEGO(r) therapy interventions; (c) published from 1996 to 2016 in a peer-reviewed
      journal, conference proceedings, or dissertation. RESULTS: Of the 6964 studies
      identified, 15 articles-involving 293 participants, aged 5-16 (mean age 8.7
      years), across five countries-met the inclusion criteria. Although the outcomes
      of the LEGO(r) therapy varied across the studies, 14 studies reported at least
      one improvement in social and communication skills (e.g., building friendships,
      improved social interactions and social competence), ASD-specific behaviors,
      belonging, family relationships, coping, and reductions in playing alone.
      CONCLUSIONS: Although LEGO(r) therapy shows promise as an intervention for
      children and youth with ASD, more rigorously designed studies are needed to fully
      understand its impact.

PMID- 27863930
TI  - [An atypical presentation of human brucellosis].

PMID- 27863929
TI  - Global Trends in Adolescent Fertility, 1990-2012, in Relation to National Wealth,
      Income Inequalities, and Educational Expenditures.
AB  - PURPOSE: National wealth, income inequalities, and expenditures on education can
      profoundly influence the health of a nation's women, children, and adolescents.
      We explored the association of trends in national socioeconomic status (SES)
      indicators with trends in adolescent birth rates (ABRs), by nation and region.
      METHODS: An ecologic research design was employed using national-level data from
      the World Bank on birth rates per 1,000 women aged 15-19 years, national wealth
      (per capita gross domestic product or GDP), income inequality (Gini index), and
      expenditures on education as a percentage of GDP (EduExp). Data were available
      for 142 countries and seven regions for 1990-2012. Multiple linear regression for
      repeated measures with generalized estimating equations was used to examine
      independent associations. RESULTS: ABRs in 2012 varied >200-fold-with the highest
      rates in Sub-Saharan Africa and lowest rates in the Western Europe/Central Asia
      region. The median national ABR fell 40% from 72.4/1,000 in 1990 to 43.6/1,000 in
      2012. The largest regional declines in ABR occurred in South Asia (70%),
      Europe/Central Asia (63%), and the Middle East/North Africa (53%)-regions with
      lower income inequality. In multivariable analyses considering change over time,
      ABRs were negatively associated with GDP and EduExp and positively associated
      with greater income inequality. CONCLUSIONS: ABRs have declined globally since
      1990. Declines closely followed rising socioeconomic status and were greater
      where income inequalities were lower in 1990. Reducing poverty and income
      inequalities and increasing investments in education should be essential
      components of national policies to prevent adolescent childbearing.

PMID- 27863932
TI  - Late-onset folie a deux in monozygotic twins.

PMID- 27863933
TI  - Lifestyle factors may be linked to symptoms of metabolic syndrome in people at
      risk for psychosis.

PMID- 27863931
TI  - The Multibiome: The Intestinal Ecosystem's Influence on Immune Homeostasis,
      Health, and Disease.
AB  - Mammalian evolution has occurred in the presence of mutualistic, commensal, and
      pathogenic micro- and macro-organisms for millennia. The presence of these
      organisms during mammalian evolution has allowed for intimate crosstalk between
      these colonizing species and the host immune system. In this review, we introduce
      the concept of the 'multibiome' to holistically refer to the biodiverse
      collection of bacteria, viruses, fungi and multicellular helminthic worms
      colonizing the mammalian intestine. Furthermore, we discuss new insights into
      multibiome-host interactions in the context of host-protective immunity and
      immune-mediated diseases, including inflammatory bowel disease and multiple
      sclerosis. Finally, we provide reasons to account for the multibiome in
      experimental design, analysis and in therapeutic applications.

PMID- 27863934
TI  - Child death and maternal psychosis-like experiences in 44 low- and middle-income
      countries: The role of depression.
AB  - BACKGROUND: Studies on the effect of child death on the mental wellbeing of women
      in low- and middle-income countries (LMICs) are scarce despite the high child
      mortality rates. Thus, the aim of the current study was to assess the association
      between child death and psychosis-like experiences (PLEs), as well as the role of
      depression in this association. METHODS: Data from 44 LMICs which participated in
      the World Health Survey (WHS) were analyzed. A total of 59,444 women who ever
      gave birth, aged 18-49years, without a self-reported lifetime psychosis
      diagnosis, were included in the analysis. The World Mental Health Survey version
      of the Composite International Diagnostic Interview (CIDI) was used to establish
      the diagnosis of past 12-month DSM-IV depression, and assess four positive
      psychotic symptoms. Depression was defined as self-reported lifetime depression
      diagnosis and/or past 12-month depression. Multivariable logistic regression
      analyses were performed. RESULTS: After adjustment for potential confounders,
      women who experienced child death had higher odds for all types of PLEs (when
      unadjusted for depression) (OR 1.20-1.71; p<0.05) and depression (OR=1.64;
      95%CI=1.39-1.93). When adjusted for depression, only delusion of control was
      strongly associated with child death (OR=1.54; 95%CI=1.20-1.97). CONCLUSIONS:
      Child death may be an important determinant of mental wellbeing among women in
      LMICs. Given the known adverse health outcomes associated with PLEs and
      depression, as well as the co-occurrence of these symptoms, mental health care
      may be particularly important for mothers who have experienced child loss in
      LMICs.

PMID- 27863936
TI  - Measurements of time intervals after in-hospital cardiac arrest give important
      information but can be further improved.

PMID- 27863935
TI  - Association of sFlt-1 and worsening psychopathology in relatives at high risk for
      psychosis: A longitudinal study.
AB  - BACKGROUND: Angiogenic dysfunction and abnormalities in psychopathology and brain
      structure have been reported in schizophrenia, but their relationships are mostly
      unknown. We recently demonstrated that sFlt-1, anti-angiogenic factor, was
      significantly elevated in patients at familial high-risk for psychosis (FHR). We
      hypothesized that elevated sFlt-1 correlates with baseline and longitudinal
      changes in psychopathology, cognition, and brain structure. METHODS: Plasma sFlt
      1 in FHR (n=35) and HC (n=39) was obtained at baseline. Schizotypal, cognitive,
      soft neurologic signs, and structural brain imaging (1.5T T1-weighted MRI,
      FreeSurfer software) measures were obtained in both groups. Longitudinal clinical
      and brain structural measures were obtained in a subgroup of FHR patients.
      Baseline data analysis used correlations between sFlt-1 and clinical/imaging
      measures and adjusted for multiple corrections. Linear mixed-effects models
      described differences in trajectories between high sFlt-1 and low sFlt-1.
      RESULTS: Baseline sFlt-1 was significantly correlated with soft neurologic signs
      (r=0.27, p=0.02) and right entorhinal volume (r=0.50, p=0.02), but not other
      baseline clinical/brain structural measures. Longitudinal examination of the FHR
      group (sFlt-1 high, n=14; sFlt-1 low, n=14) demonstrated that high sFlt-1 was
      significantly associated with worsening schizotypal symptoms (t=2.4, p=0.018).
      Reduced right hippocampal/parahippocampal volume/thickness trajectories were
      observed in high versus low sFlt-1 groups. CONCLUSIONS: The findings from this
      FHR study demonstrate that peripheral markers of angiogenic dysfunction can
      predict longitudinal clinical and brain structural changes. Also, these findings
      further support the hypothesis of altered microvascular circulation in
      schizophrenia and those at risk.

PMID- 27863937
TI  - Corrigendum to "Clinical Experience of Contrast Venography Guided Axillary Vein
      Puncture in Biventricular Pacing" [Int. J. Cardiol. 92 (2003) 55-58].

PMID- 27863938
TI  - Corrigendum to "One-quarter standard-dose ticagrelor better than standard-dose
      clopidogrel in Chinese patients with stable coronary artery disease: A
      randomized, single-blind, crossover clinical study" [Int. J. Cardiol. 215 (2016)
      209-213].

PMID- 27863939
TI  - All cause mortality and body mass index in a young Asian occupational cohort
      without baseline metabolic syndrome components: Methodological issues.

PMID- 27863940
TI  - Acute fluoride poisoning alters myocardial cytoskeletal and AMPK signaling
      proteins in rats.
AB  - BACKGROUND: Our previous findings revealed that increased oxidative stress,
      apoptosis and necrosis were implicated in acute fluoride (F-) induced cardiac
      dysfunction apart from hypocalcemia and hyperkalemia. Cardiac intermediate
      filaments (desmin and vimentin) and cytoskeleton linker molecule vinculin plays
      an imperative role in maintaining the architecture of cardiac cytoskeleton. In
      addition, AMPK is a stress activated kinase that regulates the energy homeostasis
      during stressed state. The present study was aimed to examine the role of
      cytoskeletal proteins and AMPK signaling molecules in acute F- induced
      cardiotoxicity in rats. METHODS: In order to study this, male Wistar rats were
      treated with single oral doses of 45 and 90mg/kgF- for 24h. RESULTS: Acute F-
      intoxicated rats showed declined cytoskeletal protein expression of desmin,
      vimentin and vinculin in a dose dependent manner compared to control. A
      significant increase in phosphorylation of AMPKalpha (Thr172), AMPKbeta1 (Ser108)
      and Acetyl-coA carboxylase (ACC) (Ser79) in the myocardium and associated ATP
      deprivation were found in acute F- intoxicated rats. Further, ultra-structural
      studies confirmed myofibril lysis with interruption of Z lines, dilated
      sarcoplasmic reticulum and damaged mitochondrion were observed in both the groups
      of F- intoxicated rats. CONCLUSION: Taken together, these findings reveal that
      acute F- exposure causes sudden heart failure by altering the expression of
      cytoskeletal proteins and AMPK signaling molecules.

PMID- 27863941
TI  - The l-arginine/NO pathway in the MELAS syndrome: An insufficiently explored and
      controversial research area.

PMID- 27863942
TI  - What is really meant by "complete mesocolic excision?"

PMID- 27863943
TI  - Surgical management of chronic mesh infection following incisional hernia repair.

PMID- 27863944
TI  - How to introduce a program of Enhanced Recovery after Surgery? The experience of
      the CAPIO group.
AB  - The traditional model of hospital care has been challenged by the development of
      a care-management process that allows early patient autonomy (outpatient surgery,
      Enhanced Recovery after Surgery). Hospitalization has been transformed in
      response to this development, based on innovative medical and organizational
      strategies. Within a surgical service, the deployment of these processes requires
      the creation of a support structure, with re-organization of existing structures,
      analysis of potential obstacles, implementation of management tools, and ongoing
      follow-up of organizational function, clinical results, organizational and
      patient satisfaction. These will ultimately assess adaptation of structures
      within these new organizations. In this article, we share our insights based on
      experience gained over the past six years by surgical teams of the CAPIO group.

PMID- 27863945
TI  - Intussuscepted pancreatico-gastric anastomosis: A reproducible technique.

PMID- 27863946
TI  - Should CT scan be performed when CRP is elevated after colorectal surgery?
      Results from the inflammatory markers after colorectal surgery study.
AB  - INTRODUCTION: Serum concentration of C-reactive protein (CRP) that exceeds a pre
      defined threshold between the 3rd and 5th postoperative day is a reliable marker
      of infectious complications after colorectal surgery. However, the optimal
      strategy to follow when a high CRP is found has not been defined. The aim of this
      study was to analyze the usefulness of computed tomography (CT) scan in this
      situation in a prospective cohort of patients following colorectal surgery.
      METHODS: Between November 2011 and April 2015, patients at two surgical centers
      who had undergone elective colorectal resection with anastomosis and who had a
      CRP>12.5mg/dL on the 4th postoperative day (POD) were prospectively included in a
      database. Data were collected concerning all complications occurring during the
      30days following surgery, method of diagnosis, management and clinical course.
      The decision to perform a CT scan between POD 4 and POD 6 day was guided only by
      the elevation of CRP in the absence of any other clinical signs; results were
      analyzed to evaluate the diagnostic value of elevated CRP. Uni- and multivariable
      analyses were performed to identify risk factors for postoperative infection.
      RESULTS: The study included a total of 174 patients: 56 (32.1%) had a CT between
      POD 4 and 6, and this helped detect a postoperative complication in 55.4% of
      cases. Patients who did not undergo CT had lower CRP values (16.3 vs. 18.5,
      P=0.02). Among the 118 patients who did not undergo CT, 50.8% eventually
      developed an infectious complication. The sensitivity of CRP-guided CT was 76.7%
      with a negative predictive value of 78.8%. CONCLUSION: If an elevated CRP is
      found on POD 4, an abdominopelvic CT should be performed. A normal result does
      not formally eliminate the existence of intra-abdominal complication. A study
      protocol should be set up to evaluate whether systematic revisional surgery or
      repeat CT scan is the appropriate management if CRP in the next two days reveals
      persistent inflammation.

PMID- 27863947
TI  - The effects of low-dose radiotherapy on fresh osteochondral allografts: An
      experimental study in rabbits.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of low-dose
      fractionated radiotherapy on cartilage degeneration after distal femoral fresh
      massive osteochondral allograft transplantation. METHODS: Twenty-four New Zealand
      White rabbits were divided into three groups of 8 rabbits each. All rabbits
      underwent distal femoral medial condyle fresh massive osteochondral allograft
      transplantation from California rabbits. The group 1 underwent transplantation
      without any preliminary process. The group 2 underwent fractionated local
      radiotherapy of 100 cGy for five days starting on the transplantation day. The
      group 3 included the rabbits to which the grafts transplanted after radiating in
      vitro by a single dose radiation of 1500 cGy. The hosts were sacrificed twelve
      weeks later. Anteroposterior and lateral radiographs were taken. Synovial tissue,
      cartilaginous tissue, and subchondral bone were assessed histopathologically.
      RESULTS: Nonunion was present in three cases of group 2 and one of group 3 in
      which cartilage degeneration was more severe. Synovial hypertrophy and pannus
      formation were more obvious in non-radiated rabbits. Hypocellularity and necrosis
      of the subchondral bone were rare in group 2. More cartilage tissue impairment
      was present in group 3 compared to group 1. CONCLUSION: In osteochondral massive
      allograft transplantations, the immune reaction of the host could be precluded
      with radiotherapy, and the side-effects can be prevented by low-dose fractionated
      regimen. The total dose of fractionated radiotherapy for an immune suppression
      should be adjusted not to damage the cartilage tissue, but to avoid articular
      degeneration in the long term.

PMID- 27863948
TI  - Tree-structured survival analysis of patients with Pseudomonas aeruginosa
      bacteremia: A multicenter observational cohort study.
AB  - This study aimed to construct a prediction algorithm, which is readily applicable
      in the clinical setting, to determine the mortality rate for patients with P.
      aeruginosa bacteremia. A multicenter observational cohort study was performed
      retrospectively in seven university-affiliated hospitals in Korea from March 2012
      to February 2015. In total, 264 adult patients with monomicrobial P. aeruginosa
      bacteremia were included in the analyses. Among the predictors independently
      associated with 30-day mortality in the Cox regression model, Pitt bacteremia
      score >2 and high-risk source of bacteremia were identified as critical nodes in
      the tree-structured survival analysis. Particularly, the empirical combination
      therapy was not associated with any survival benefit in the Cox regression model
      compared to the empirical monotherapy. This study suggests that determining the
      infection source and evaluating the clinical severity are critical to predict the
      clinical outcome in patients with P. aeruginosa bacteremia.

PMID- 27863949
TI  - Imipenem-avibactam: a novel combination for the rapid detection of carbapenemase
      activity in Enterobacteriaceae and Acinetobacter baumannii by matrix-assisted
      laser desorption ionization-time of flight mass spectrometry.
AB  - In the present study, we propose a novel matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS)-based method for
      detecting carbapenemase-producing Enterobacteriaceae and Acinetobacter baumannii.
      For this, we analyzed a series of 131 isolates. Among them, a total of 115
      Enterobacteriaceae: 79 of them carrying a carbapenemase enzyme (15blaKPC,
      7blaNDM, 11blaIMP, 12blaVIM, and 34blaOXA-48) and 16 A. baumannii isolates: 15 of
      them carrying carbapenemases (10blaOXA-23, 2blaOXA-58, 2blaOXA-24, and 1blaOXA
      237). The rest of the isolates were noncarbapenemase producers and used as
      negative controls. The isolates were submitted to susceptibility testing using a
      combination of imipenem-avibactam and analysis by the MALDI-TOF Biotyper Compass
      software (Bruker Daltonik, Germany). The assay showed an overall sensitivity and
      specificity for carbapenemase detection of 98% and 100%, respectively. The
      combination of imipenem and avibactam displayed activity against KPC and OXA-48
      producing Enterobacteriaceae and thus represents a new strategy for identifying
      and confirming these carbapenemases. However, the combination did not provide any
      benefit over A. baumannii.

PMID- 27863950
TI  - Evaluation of the SHIGA TOXIN QUIK CHEK and ImmunoCard STAT! EHEC as screening
      tools for the detection of Shiga toxin in fecal specimens.
AB  - In this study we evaluated the performance of the SHIGA TOXIN QUIK CHEK
      (Techlab(r), Blacksburg, VA) and the ImmunoCard STAT! Enterohaemorrhagic E. coli
      (EHEC) (Meridian BioScience, Cincinnati, OH, USA) assays as methods for
      qualitatively detecting the presence of Shiga toxin in human fecal specimens. A
      multiplex PCR for the detection of stx1 and stx2 was used as the standard for
      comparison. The SHIGA TOXIN QUIK CHEK detected all known Shiga toxin subtypes
      with the exception of Stx2f, while the ImmunoCard STAT! EHEC was unable to
      identify four of the seven Stx2 subtypes, including Stx2b and Stx2d. When
      compared to multiplex PCR based on Shiga toxin gene presence alone both assays
      demonstrated 100% specificity, and gave sensitivity values of 50.0% and 41.2%
      respectively. Correlation between each assay and the multiplex PCR was calculated
      by the use of kappa, with both assays exhibiting a moderate level of agreement.

PMID- 27863951
TI  - Detection of Helicobacter pylori and the genotypes of resistance to
      clarithromycin and the heterogeneous genotype to this antibiotic in biopsies
      obtained from symptomatic children.
AB  - : The aim of this study was to use a commercially available kit (GenoType(r)
      HelicoDR; Hain Life Science, Germany) to detect Helicobacter pylori infection and
      clarithromycin resistance genotype in biopsies obtained from symptomatic
      children. RESULTS: 111 out of 136 (81.6%) biopsies were H. pylori positive by
      genotype: 47 (42.3%) showed wild-type genotype, 53 resistant genotype (47.7%) and
      11 heterogeneous genotype (9.9%). Culture was negative in 27 out of the 111
      genotyped biopsies. Mutation A2143G (87.5%), followed by A2142G (7.5%) and double
      mutant A2142C-A2143G (5%) were found. The 11 heterogeneous genotype biopsies
      showed wild-type plus A2143G in 9 and plus A2142G in 2. CONCLUSIONS: This kit is
      a rapid, culture-independent method for routine application in biopsies from the
      pediatric population that allows detection of clarithromycin resistance and
      heterogeneous genotypes. It is important to know the clinical impact of infection
      with this type of strains as well as the role in treatment success.

PMID- 27863952
TI  - Differences in the dynamics of affective and cognitive processing - An ERP study.
AB  - A controversy in emotion research concerns the question of whether affective or
      cognitive primacy are evident in processing affective stimuli and the factors
      contributing to each alternative. Using electrophysiological recordings in an
      adapted visual oddball paradigm allowed tracking the dynamics of affective and
      cognitive effects. Stimuli consisted of face pictures displaying affective
      expressions with rare oddballs differing from frequent stimuli in either
      affective expression, structure (while frequent stimuli were shown frontally
      these deviants were turned sideways) or they differed on both dimensions, i.e. in
      affective expression and structure. Results revealed a defined sequence of
      differences in ERP amplitudes: For stimuli deviating in their affective
      expression only, P1 modulations ~100ms were evident, while affective differences
      of structure deviants were not evident before the N170 time window. All three
      types of deviants differed in P300 amplitudes, indicating integration of
      affective and structural information. These results encompass evidence for both,
      cognitive and affective primacy depending on stimulus properties. Specifically
      affective primacy is only visible when the respective facial features can be
      extracted with ease. When structural differences make face processing harder,
      however, cognitive primacy is brought forward.

PMID- 27863953
TI  - Reliability of a Kid's Activity and Nutrition Questionnaire for School-Based SNAP
      Ed Interventions as Part of a Tiered Development Process.
AB  - OBJECTIVE: To assess the reliability of the Kids' Activity and Nutrition
      Questionnaire (KAN-Q) as part of a tiered process for developing Supplemental
      Nutrition Assistance Program-Education tools. METHODS: The KAN-Q was administered
      at 2 time points to assess internal consistency using standardized values of
      Cronbach alpha and test-retest reliability using the intraclass correlation
      coefficient for continuous variables, Cohen's kappa (kappa) statistic for
      categorical variables, and the weighted kappa statistic for ordinal data.
      RESULTS: Data were collected from 119 fourth graders. Cronbach alpha was adequate
      for behavior (.71) and knowledge (.72) scales and nutrition behavior (.78) and
      nutrition knowledge (.75) subscales. Test-retest reliability was generally
      acceptable, with intraclass correlation coefficients from 0.40 to 0.75 and kappa
      coefficients showing fair to substantial agreement (0.30 to 0.72). CONCLUSIONS
      AND IMPLICATIONS: The KAN-Q is a practical and reliable questionnaire for school
      based administration that aligns directly with Supplemental Nutrition Assistance
      Program-Education evaluation priorities.

PMID- 27863954
TI  - Cardiovascular disease biomarkers on cognitive function in older adults: Joint
      effects of cardiovascular disease biomarkers and cognitive function on mortality
      risk.
AB  - Previous research demonstrates an inverse association between age and
      cardiovascular disease (CVD) biomarkers with cognitive function; however, little
      is known about the combined associations of CVD risk factors and cognitive
      function with all-cause mortality in an older adult population, which was the
      purpose of this study. Data from the 1999-2002 NHANES were used (N=2,097;
      60+yrs), with mortality follow-up through 2011. Evaluated individual biomarkers
      included mean arterial pressure (MAP), high-sensitivity C-reactive protein (CRP),
      HDL-C, total cholesterol (TC), A1C, and measured body mass index (BMI). Cognitive
      function was assessed using the Digit Symbol Substitution Test (DSST). Further, 4
      groups were created based on CVD risk and cognitive function. Group 1: high
      cognitive function and low CVD risk; Group 2: high cognitive function and high
      CVD risk; Group 3: low cognitive function and low CVD risk; Group 4: low
      cognitive function and high CVD risk. An inverse relationship was observed where
      those with more CVD risk factors had a lower (worse) cognitive function score.
      Compared to those in Group 1, only those in Group 3 and 4 had an increase
      mortality risk.

PMID- 27863955
TI  - The BLUEPRINT Data Analysis Portal.
AB  - The impact of large and complex epigenomic datasets on biological insights or
      clinical applications is limited by the lack of accessibility by easy, intuitive,
      and fast tools. Here, we describe an epigenomics comparative cyber-infrastructure
      (EPICO), an open-access reference set of libraries to develop comparative
      epigenomic data portals. Using EPICO, large epigenome projects can make available
      their rich datasets to the community without requiring specific technical skills.
      As a first instance of EPICO, we implemented the BLUEPRINT Data Analysis Portal
      (BDAP). BDAP provides a desktop for the comparative analysis of epigenomes of
      hematopoietic cell types based on results, such as the position of epigenetic
      features, from basic analysis pipelines. The BDAP interface facilitates
      interactive exploration of genomic regions, genes, and pathways in the context of
      differentiation of hematopoietic lineages. This work represents initial steps
      toward broadly accessible integrative analysis of epigenomic data across
      international consortia. EPICO can be accessed at https://github.com/inab, and
      BDAP can be accessed at http://blueprint-data.bsc.es.

PMID- 27863956
TI  - The International Human Epigenome Consortium Data Portal.
AB  - The International Human Epigenome Consortium (IHEC) coordinates the production of
      reference epigenome maps through the characterization of the regulome, methylome,
      and transcriptome from a wide range of tissues and cell types. To define
      conventions ensuring the compatibility of datasets and establish an
      infrastructure enabling data integration, analysis, and sharing, we developed the
      IHEC Data Portal (http://epigenomesportal.ca/ihec). The portal provides access to
      >7,000 reference epigenomic datasets, generated from >600 tissues, which have
      been contributed by seven international consortia: ENCODE, NIH Roadmap, CEEHRC,
      Blueprint, DEEP, AMED-CREST, and KNIH. The portal enhances the utility of these
      reference maps by facilitating the discovery, visualization, analysis, download,
      and sharing of epigenomics data. The IHEC Data Portal is the official source to
      navigate through IHEC datasets and represents a strategy for unifying the
      distributed data produced by international research consortia.

PMID- 27863957
TI  - Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity
      studies of p-tertbutylcalix[4]arene nanoemulsion for radiation decontamination.
AB  - AIMS: p-tertbutylcalix[4]arene loaded nanoemulsion has been designed,
      characterized and evaluated for skin decontamination of radionuclides of interest
      in nuclear and radiological emergencies. Further, nanoemulsion was evaluated for
      Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity.
      MATERIALS AND METHODS: Ex-vivo skin complexation studies were conducted using
      High-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF
      ICPMS). Skin studies at dermal and cyto-dermal level have been carried out using
      techniques such as florescence microscopy, Differential scanning calorimetry
      (DSC), Flow cytometry, Confocal microscopy, Prestoblue and Comet assay. KEY
      FINDINGS: HR-SF-ICPMS study confirmed >95% complexation of surrogate nuclides of
      thallium and Iodine applied on excised rat skin mounted over Franz diffusion
      cell. Temporal analysis of aliquots obtained from Franz diffusion cell using UV
      Vis absorption spectroscopy indicated that only 3.37% of formulation permeates
      through the skin. Skin penetration study of rhodamine 123 nanoemulsion carried
      out using florescence microscopy confirmed that formulation remains localised in
      epidermis of rat skin. DSC data confirmed skin compatibility of nanoemulsion, as
      no lipid extraction was observed from skin. In-vitro cell viability and cellular
      uptake assays performed on human skin fibroblasts prove no cellular uptake and
      cytotoxic effects. Comet assay, cell cycle arrest, and apoptosis-inducing
      mechanistic studies prove that prepared nanoemulsion is safe at cellular level.
      SIGNIFICANCE: Taken together, data indicate that p-tertbutylcalix[4]arene
      nanoemulsion is both effective and safe formulation to use on skin for radio
      decontamination.

PMID- 27863958
TI  - The expression of bitter taste receptors in mesenteric, cerebral and omental
      arteries.
AB  - AIM: Bitter taste is sensed by the bitter taste receptor (TAS2R), which is mainly
      expressed in the tongue as well as in extra-oral organs, such as the
      gastrointestinal tract, respiratory tract, brain, heart and testis. This study
      aimed to investigate whether TAS2R is expressed in the mesenteric, cerebral and
      omental arteries. MAIN METHODS: The expression levels of TAS2R mRNA and protein
      were determined by reverse-transcription polymerase chain reaction and Western
      blotting, respectively. The location of TAS2R was determined by
      immunofluorescence imaging. TAS2R agonists were used in a sensitive myograph to
      study the function of TAS2R in arteries. KEY FINDINGS: The mRNA of rat TAS2Rs,
      including rTAS2R39, rTAS2R40, rTAS2R108, rTAS2R114, rTAS2R130, rTAS2R137, and
      rTAS2R140, was expressed in rat mesenteric and cerebral arteries, but rTAS2R114
      was not expressed in the cerebral arteries. The mRNA of human TAS2Rs, including
      hTAS2R3, hTAS2R4, hTAS2R7, hTAS2R10, hTAS2R14, hTAS2R39 and hTAS2R40, was
      expressed in human omental arteries. The TAS2R7 protein was expressed in rat
      mesenteric and cerebral arteries, as well as in human omental arteries.
      Immunofluorescence imaging confirmed that TAS2R7 was located in vascular smooth
      muscle cells and endothelial cells. The TAS2R agonists, chloroquine and quinine
      relaxed rat mesenteric arteries and cerebral arteries and human omental arteries
      in a concentration-dependent manner. SIGNIFICANCE: TAS2R is expressed in the
      arteries of systemic circulation, including rat mesenteric and cerebral arteries
      and human omental arteries. This study provides evidence that TAS2R do exist in
      the arteries and may be involved in the mediation of vessel functions.

PMID- 27863960
TI  - Route of transmission of Staphylococcus aureus.

PMID- 27863959
TI  - Transmission of Staphylococcus aureus between health-care workers, the
      environment, and patients in an intensive care unit: a longitudinal cohort study
      based on whole-genome sequencing.
AB  - BACKGROUND: Health-care workers have been implicated in nosocomial outbreaks of
      Staphylococcus aureus, but the dearth of evidence from non-outbreak situations
      means that routine health-care worker screening and S aureus eradication are
      controversial. We aimed to determine how often S aureus is transmitted from
      health-care workers or the environment to patients in an intensive care unit
      (ICU) and a high-dependency unit (HDU) where standard infection control measures
      were in place. METHODS: In this longitudinal cohort study, we systematically
      sampled health-care workers, the environment, and patients over 14 months at the
      ICU and HDU of the Royal Sussex County Hospital, Brighton, England. Nasal swabs
      were taken from health-care workers every 4 weeks, bed spaces were sampled
      monthly, and screening swabs were obtained from patients at admission to the ICU
      or HDU, weekly thereafter, and at discharge. Isolates were cultured and their
      whole genome sequenced, and we used the threshold of 40 single-nucleotide
      variants (SNVs) or fewer to define subtypes and infer recent transmission.
      FINDINGS: Between Oct 31, 2011, and Dec 23, 2012, we sampled 198 health-care
      workers, 40 environmental locations, and 1854 patients; 1819 isolates were
      sequenced. Median nasal carriage rate of S aureus in health-care workers at 4
      weekly timepoints was 36.9% (IQR 35.7-37.3), and 115 (58%) health-care workers
      had S aureus detected at least once during the study. S aureus was identified in
      8-50% of environmental samples. 605 genetically distinct subtypes were identified
      (median SNV difference 273, IQR 162-399) at a rate of 38 (IQR 34-42) per 4-weekly
      cycle. Only 25 instances of transmission to patients (seven from health-care
      workers, two from the environment, and 16 from other patients) were detected.
      INTERPRETATION: In the presence of standard infection control measures, health
      care workers were infrequently sources of transmission to patients. S aureus
      epidemiology in the ICU and HDU is characterised by continuous ingress of
      distinct subtypes rather than transmission of genetically related strains.
      FUNDING: UK Medical Research Council, Wellcome Trust, Biotechnology and
      Biological Sciences Research Council, UK National Institute for Health Research,
      and Public Health England.

PMID- 27863961
TI  - Glycan region of GPI anchored-protein is required for cytocidal oligomerization
      of an anticancer parasporin-2, Cry46Aa1 protein, from Bacillus thuringiensis
      strain A1547.
AB  - Parasporin-2 (PS2), alternatively named Cry46Aa1, an anticancer protein derived
      from Bacillus thuringiensis strain A1547, causes specific cell damage via PS2
      oligomerization in the cell membrane. Although PS2 requires
      glycosylphosphatidylinositol (GPI)-anchored proteins for its cytocidal action,
      their precise role is unknown. Here, we report that the glycan of GPI induces PS2
      oligomerization, which causes cell death. Cytotoxicity, cell-binding and
      oligomerization of the toxin were not observed in GPI-anchored protein-deficient
      Chinese hamster ovary cells. Expression and protease-treatment analyses showed
      that the actions of the toxin were dependent on the glycan core, not the
      polypeptide moiety, of GPI-anchored proteins. However, surface expression of some
      GPI-anchored proteins is observed in PS2-insensitive cells. These data suggest
      that GPI-anchored proteins do not determine the target specificity, but instead
      function as a kind of coreceptor, in the cytocidal action of PS2.

PMID- 27863963
TI  - The dose-response of salvage radiotherapy following radical prostatectomy: A
      systematic review and meta-analysis.
AB  - PURPOSE/OBJECTIVES: To date neither the optimal radiotherapy dose nor the
      existence of a dose-response has been established for salvage RT (SRT).
      MATERIALS/METHODS: A systematic review from 1996 to 2015 and meta-analysis was
      performed to identify the pathologic, clinical and treatment factors associated
      with relapse-free survival (RFS) after SRT (uniformly defined as a PSA>0.2ng/mL
      or rising above post-SRT nadir). A sigmoidal dose-response curve was objectively
      fitted and a non-parametric statistical test used to determine significance.
      RESULTS: 71 studies (10,034 patients) satisfied the meta-analysis criteria. SRT
      dose (p=0.0001), PSA prior to SRT (p=0.0009), ECE+ (p=0.039) and SV+ (p=0.046)
      had significant associations with RFS. Statistical analyses confirmed the
      independence of SRT dose-response. Omission of series with ADT did not alter
      results. Dose-response is well fit by a sigmoidal curve (p=0.0001) with a TCD50
      of 65.8Gy, with a dose of 70Gy achieving 58.4% RFS vs. 38.5% for 60Gy. A 2.0%
      [95% CI 1.1-3.2] improvement in RFS is achieved for each Gy. The SRT dose
      response remarkably parallels that for definitive RT of localized disease.
      CONCLUSIONS: This study provides level 2a evidence for dose-escalated SRT>70Gy.
      The presence of an SRT dose-response for microscopic disease supports the
      hypothesis that prostate cancer is inherently radio-resistant.

PMID- 27863962
TI  - Understanding the impact of pelvic organ motion on dose delivered to target
      volumes during IMRT for cervical cancer.
AB  - BACKGROUND: Advanced radiotherapy techniques reduce normal tissue dose by
      conforming closely to target volumes. In cervical cancer radiotherapy, organ
      filling affects clinical target volume (CTV; cervix, uterus) position. This study
      estimates the dosimetric effect of this primary CTV position variation during
      chemoradiation. METHODS/MATERIALS: Twice weekly cone-beam computed tomography
      (CBCT) images of ten patients undergoing cervical chemoradiation were
      retrospectively analysed. Primary CTV, bladder and rectum were delineated.
      RapidArc plans were created using 10-15mm CTV-PTV margins and dose delivered to
      CTV based on each CBCT position was calculated using a novel vector approach.
      Dose delivered along the central uterine, mid-uterus and cervix vectors were
      analysed as well as dose delivered to points at uterine tip, anterior mid-uterus
      and anterior cervix. Additional RapidArc plans were created for large planning
      bladder volume cases using the CTV acquired with bladder volume at 150-300cc.
      RESULTS: 105 scans for 10 patients were analysed. Vector analysis revealed CTV
      underdosing in certain cases. Below 95% average vector coverage was found for all
      three vectors in 2 cases and one vector in 1 case. Volumetric analysis revealed
      D99<95% in 48% of fractions. Patients with large planning bladder volumes
      (>300cc) demonstrated the largest variation. Replanning improved this coverage.
      The anterior mid-uterus point was least well-covered; median 98.7% dose, reducing
      to 91.4% in cases with large planning bladder volumes. Again, replanning
      significantly improved this. D99>95% was maintained in 93% of fractions when
      bladder volume was 50cc below to 150cc above planning volume compared to 24% of
      fractions if bladder volume was outside this range. Similarly, D95>95% was 100%
      versus 84%. CONCLUSION: Organ position variation detrimentally affected dose
      delivered to CTV including cervix. Large planning bladder volumes (>300cc) led to
      more variation. We recommend bladder volumes of 150-300cc at planning and a range
      of 50cc below to 150cc above planning for treatment.

PMID- 27863964
TI  - Clinical evidence of variable proton biological effectiveness in pediatric
      patients treated for ependymoma.
AB  - BACKGROUND AND PURPOSE: A constant relative biological effectiveness (RBE) is
      used for clinical proton therapy; however, experimental evidence indicates that
      RBE can vary. We analyzed pediatric ependymoma patients who received proton
      therapy to determine if areas of normal tissue damage indicated by post-treatment
      image changes were associated with increased biological dose effectiveness.
      MATERIAL AND METHODS: Fourteen of 34 children showed T2-FLAIR hyperintensity on
      post-treatment magnetic resonance (MR) images. We delineated regions of treatment
      related change and calculated dose and linear energy transfer (LET) distributions
      with Monte Carlo. Voxel-level image change data were fit to a generalized linear
      model incorporating dose and LET. Cross-validation was used to determine model
      parameters and for receiver operating characteristic curve analysis. Tolerance
      dose (TD50; dose at which 50% of patients would experience toxicity) was
      interpolated from the model. RESULTS: Image changes showed dependence on
      increasing LET and dose. TD50 decreased with increasing LET, indicating an
      increase in biological dose effectiveness. The cross-validated area under the
      curve for the model was 0.91 (95% confidence interval 0.88-0.94). CONCLUSIONS:
      Our correlation of changes on MR images after proton therapy with increased LET
      constitutes the first clinical evidence of variable proton biological
      effectiveness.

PMID- 27863965
TI  - Robustness of the Reichert Unistat Bilirubinometer for analysis of hemolyzed
      samples from neonates.
AB  - BACKGROUND AND OBJECTIVES: Bilirubin is routinely measured in neonates to avoid
      the irreversible effects of kernicterus. Grossly hemolyzed samples are routinely
      rejected under the assumption that bilirubin cannot be accurately measured in
      hemolyzed samples. The objective of this study was to determine the effect of
      hemolysis on bilirubin measurement in neonates. METHODS: Data included 2-years of
      paired bilirubin results (n=70) where hemolyzed and non-hemolyzed samples were
      collected and measured within 6h of each other. Bilirubin results were compared
      by Passing-Bablock linear regression and difference plots. Bilirubin results were
      also compared using the Bhutani nomogram to determine if hemolysis affected the
      hyperbilirubinemia risk-category. RESULTS: Gross hemolysis resulted in a mean
      negative bias of -5.2MUmol/L (95% CI: -30.7 to 20.3MUmol/L). Based on the Bhutani
      nomogram, 1/70 samples would have been classified as Low-intermediate instead of
      High-intermediate risk and 3/70 would have been classified as Low instead of Low
      intermediate risk; 5/70 samples would have been classified as Low-intermediate
      instead of Low risk. CONCLUSIONS: Collectively the data support that neonatal
      bilirubin may be reported from grossly hemolyzed samples measured using the
      Reichert Unistat Bilirubinometer. This practice has been adopted at our
      institution where results are reported with comments describing the effects of
      hemolysis. Implementation of this approach has decreased the number of blood re
      collections in neonates.

PMID- 27863966
TI  - Activation of telomerase by HPVs.
AB  - Telomerase extends the ends of linear chromosomes, and its expression leads to
      cellular immortalization. In HPV-associated cancers, telomerase is universally
      detected, and this occurs by activation of the catalytic subunit of telomerase,
      hTERT. The expression of hTERT is affected by both high-risk HPV E6 and E7.
      Seminal studies over the last two decades have identified the transcriptional,
      epigenetic, and post-transcriptional roles high-risk E6 and E7 have in telomerase
      regulation. This review will summarize these findings and highlight the
      importance of telomerase activation as an oncogenic pathway in HPV-associated
      cancer development and progression.

PMID- 27863968
TI  - Periocular, periorbital, and orbital pathology in liver disease.
AB  - Although the connection is not often apparent, hepatic pathology may be
      associated with ophthalmic disease. We review the literature concerning the
      periocular, periorbital, and orbital manifestations of various hepatic disorders.
      This includes periocular or periorbital jaundice, the impact of hepatitis B and
      C, eyelid changes in cirrhosis, orbital mass lesions in hepatocellular carcinoma,
      and cutaneous vascular malformations as they are related to liver disease. The
      motility disorders associated with Wilson disease, the ophthalmic manifestations
      of Alagille syndrome, and the effects of liver transplantation are also
      discussed.

PMID- 27863969
TI  - Moving forward with obesity research in breast cancer.

PMID- 27863971
TI  - Systemic inaccuracies in the National Surgical Quality Improvement Program
      database: Implications for accuracy and validity for neurosurgery outcomes
      research.
AB  - The American College of Surgeons (ACS) National Surgical Quality Improvement
      Program (NSQIP) provides a rich database of North American surgical procedures
      and their complications. Yet no external source has validated the accuracy of the
      information within this database. Using records from the 2006 to 2013 NSQIP
      database, we used two methods to identify errors: (1) mismatches between the
      Current Procedural Terminology (CPT) code that was used to identify the surgical
      procedure, and the International Classification of Diseases (ICD-9) post
      operative diagnosis: i.e., a diagnosis that is incompatible with a certain
      procedure. (2) Primary anesthetic and CPT code mismatching: i.e., anesthesia not
      indicated for a particular procedure. Analyzing data for movement disorders,
      epilepsy, and tumor resection, we found evidence of CPT code and postoperative
      diagnosis mismatches in 0.4-100% of cases, depending on the CPT code examined.
      When analyzing anesthetic data from brain tumor, epilepsy, trauma, and spine
      surgery, we found evidence of miscoded anesthesia in 0.1-0.8% of cases. National
      databases like NSQIP are an important tool for quality improvement. Yet all
      databases are subject to errors, and measures of internal consistency show that
      errors affect up to 100% of case records for certain procedures in NSQIP. Steps
      should be taken to improve data collection on the frontend of NSQIP, and also to
      ensure that future studies with NSQIP take steps to exclude erroneous cases from
      analysis.

PMID- 27863970
TI  - Treatment of distal anterior cerebral artery aneurysms with the Pipeline
      Embolization Device.
AB  - Aneurysms of the anterior cerebral artery (ACA) located distal to the anterior
      communicating artery complex (ACOM) remain challenging to treat with surgical
      clip reconstruction as well as with endovascular coil-embolization strategies. We
      have treated five complex geometry distal ACA aneurysms with endoluminal
      reconstruction using the Pipeline Embolization Device (PED). Two aneurysms were
      of the dysplastic fusiform type. Three aneurysms were of complex saccular
      configuration. Three aneurysms were treated electively at the outset with PED.
      One patient had previously undergone aborted clip reconstruction, and one was
      treated for recurrent aneurysm growth after coil embolization. The mean diameter
      of the ACA in this cohort was 1.96mm proximal to the aneurysm and 1.79mm distal
      to the aneurysmal segment. A single PED of 2.5mm inner diameter was the sole
      treatment in four cases. Two PEDs, telescopically overlapped across the aneurysm,
      were used in the remaining case. All devices were deployed successfully. No
      parent artery occlusion or stenosis was observed. In all cases an associated
      branch vessel arising from the vicinity of the aneurysm or incorporated into its
      neck was covered by the endoluminal construct. At follow-up angiography, robust
      antegrade flow was maintained in the jailed branch. One patient experienced
      asymptomatic, delayed occlusion of the jailed branch. Complete aneurysm occlusion
      was seen in all patients. We confirm that PED can be deployed in parent vessels
      smaller than 2mm diameter, and that endoluminal reconstruction with the PED may
      be a safe and effective treatment alternative for selected distal ACA aneurysms.

PMID- 27863972
TI  - Vagus nerve stimulator-related speech/exercise induced cough.
AB  - Vagal nerve stimulation (VNS) therapy is an effective adjunctive treatment for
      chronic or recurrent treatment resistant depression. Although considered a safe
      procedure, increasing output current can be associated with stimulation induced
      side effects. We report the first case of dry cough induced by speech and mild
      exercise, occurring in the off mode following implantation of a vagal nerve
      stimulator (VNSor). We discuss the possible pathophysiology and the potential
      treatment options of this rare complication.

PMID- 27863973
TI  - White blood cell subtypes and risk of type 2 diabetes.
AB  - OBJECTIVE: It is reported that total white blood cell is associated with risk of
      diabetes mellitus. The present study is to investigate the relationship of white
      blood cell subsets with incidence of type 2 diabetes at baseline and 3year follow
      up. METHODS: We chose individuals without diabetes history as our study
      population; 8991 individuals were included at baseline. All of the participants
      underwent a 75-g OGTT at baseline. White blood cell count including all the
      subsets were measured along with all the other laboratory indices. The
      participants who were not diagnosed with type 2 diabetes according to the WHO
      1999 diagnostic criteria underwent another 75-g OGTT at 3year follow-up. RESULTS:
      The total WBC count, neutrophil count, and lymphocyte count were significantly
      increased in subjects newly diagnosed with diabetes mellitus compared to non-DM
      subjects at baseline (all p<0.001). The ORs for DM were increased from the 1st to
      the 4th quartiles at both baseline and follow-up (both p<0.001 for trend). At
      baseline, in the highest WBC quartile, the adjusted OR of DM was 2.51 (95%
      confidence interval [CI] 2.09 to 3.02). In the highest neutrophils quartile, the
      adjusted OR of DM was 2.11 (95% confidence interval [CI] 1.78 to 2.51). In the
      highest lymphocytes quartile, the adjusted OR of DM was 1.85 (95% confidence
      interval [CI] 1.56 to 2.18). At follow-up, in the highest WBC quartile, the
      adjusted OR of DM was 1.79 (95% confidence interval [CI] 1.38 to 2.33). In the
      highest neutrophils quartile, the adjusted OR of DM was 1.58 (95% confidence
      interval [CI] 1.23 to 2.03). In the highest lymphocytes quartile, the adjusted OR
      of DM was 1.74 (95% confidence interval [CI] 1.37 to 2.22). HOMA-IR and HbA1c
      correlated to elevated levels of WBC count, neutrophils and lymphocytes
      significantly (all p<0.001). CONCLUSIONS: Increased levels of WBC count,
      neutrophils and lymphocytes are all predictors for incidence of type 2 diabetes.

PMID- 27863974
TI  - Establishment of Aedes aegypti (L.) in mountainous regions in Mexico: Increasing
      number of population at risk of mosquito-borne disease and future climate
      conditions.
AB  - The study was conducted in the central region of Veracruz Mexico, in the
      metropolitan area of Xalapa. It is a mountainous area where Aedes aegypti (L.) is
      not currently endemic. An entomological survey was done along an elevation
      gradient using the Ae. aegypti occurrences at different life cycle stages. Seven
      sites were sampled and a total of 24 mosquito species were recorded: 9 species
      were found in urban areas, 18 in non-urban areas with remnant vegetation, and 3
      occurred in both environments. Ae. aegypti was found only in the urban areas,
      usually below 1200m a.s.l., but in this study was recorded for the first time at
      1420m a.s.l. These occurrences, together with additional distribution data in the
      state of Veracruz were used to developed species distribution models using
      Maxlike software in R to identify the current projected suitable areas for the
      establishment of this vector and the human populations that might be affected by
      dengue transmission at higher elevations. Its emergence in previously unsuitable
      places appears to be driven by both habitat destruction and biodiversity loss
      associated with biotic homogenization. A border study using data from the edges
      of the vector's distribution might allow sensitive monitoring to detect any
      changes in this mosquito's distribution pattern, and any changes in the anthropic
      drivers or climate that could increase transmission risk.

PMID- 27863967
TI  - Host cell restriction factors that limit transcription and replication of human
      papillomavirus.
AB  - The life cycle of human papillomaviruses (HPV) is tightly regulated by the
      differentiation state of mucosal and cutaneous keratinocytes. To counteract viral
      infection, constitutively expressed cellular factors, which are defined herein as
      restriction factors, directly mitigate viral gene expression and replication. In
      turn, some HPV gene products target these restriction factors and abrogate their
      anti-viral effects to establish efficient gene expression and replication
      programs. Ironically, in certain circumstances, this delicate counterbalance
      between viral gene products and restriction factors facilitates persistent
      infection by HPVs. This review serves to recapitulate the current knowledge of
      nuclear restriction factors that directly affect the HPV infectious cycle.

PMID- 27863975
TI  - Brief Academic Bio of the Senior Guest Editor: Dr Jerard Seghatchian.

PMID- 27863976
TI  - Postoperative hyperglycaemia control reduces postoperative complications in
      patients subject to total knee arthroplasty.
AB  - BACKGROUND: The aim of our study was the early detection and treatment of
      patients with unknown alterations of the hydrocarbon metabolism subject to total
      knee arthroplasty in order to reduce the incidence of postoperative
      complications. METHODS: Patients were classified as non-diabetic patients (group
      1), diabetic patients (group 2) and patients with stress hyperglycaemia (group
      3). The last two groups were recommended assessment by a primary care physician
      (PCP). After one year follow-up the groups were compared with respect to
      incidence of postoperative complications. The groups were also compared regarding
      the decrease or increase of HbA1c levels with the incidence of complications.
      RESULTS: Of the 228 patients, 116 (50%) were included in group 1, 40 (17.5%) in
      group 2 and 72 (31.6%) in group 3. Patients that consulted their PCP presented
      lower medical complication rates than those who did not (9.2% vs. 26.4%,
      P=0.020). Not being attended by a PCP was an independent predictive factor of
      medical complication (odds ratio (OR): 21.3; 95% confidence interval (95% CI):
      4.6-98.5), surgical site infection (OR: 4.1; 95% CI: 1.1-15.0) and mechanical
      complication (OR: 5.0; 95% CI: 1.3-18.8). A decrease of HbA1c value was related
      to less medical systemic complications (7.3% vs. 24.2%, P=0.035). CONCLUSIONS:
      Patients with hyperglycaemia during the postoperative total knee arthroplasty
      period, who are controlled by the PCP present lower incidence of complications.
      Decrease of HbA1c value during postoperative total knee arthroplasty period leads
      to a lower rate of medical complications.

PMID- 27863977
TI  - Foreword.

PMID- 27863978
TI  - Predicting the physiological response of Tivela stultorum hearts with digoxin
      from cardiac parameters using artificial neural networks.
AB  - Multi-layer perceptron artificial neural networks (MLP-ANNs) were used to predict
      the concentration of digoxin needed to obtain a cardio-activity of specific
      biophysical parameters in Tivela stultorum hearts. The inputs of the neural
      networks were the minimum and maximum values of heart contraction force, the time
      of ventricular filling, the volume used for dilution, heart rate and weight,
      volume, length and width of the heart, while the output was the digoxin
      concentration in dilution necessary to obtain a desired physiological response.
      ANNs were trained, validated and tested with the dataset of the in vivo
      experiment results. To select the optimal network, predictions for all the
      dataset for each configuration of ANNs were made, a maximum 5% relative error for
      the digoxin concentration was set and the diagnostic accuracy of the predictions
      made was evaluated. The double-layer perceptron had a barely higher performance
      than the single-layer perceptron; therefore, both had a good predictive ability.
      The double-layer perceptron was able to obtain the most accurate predictions of
      digoxin concentration required in the hearts of T. stultorum using MLP-ANNs.

PMID- 27863980
TI  - The need for international consensus on prediabetes.

PMID- 27863979
TI  - Comparative prognostic performance of definitions of prediabetes: a prospective
      cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study.
AB  - BACKGROUND: No consensus on definitions of prediabetes exists among international
      organisations. Analysis of associations with different definitions and clinical
      complications can inform the comparative value of different prediabetes
      definitions. We compared the risk of future outcomes across different prediabetes
      definitions based on fasting glucose concentration, HbA1c, and 2 h glucose
      concentration during over two decades of follow-up in the community-based
      Atherosclerosis Risk in Communities (ARIC) study. We aimed to analyse the
      associations of definitions with outcomes to provide a comparison of different
      definitions. METHODS: We did a prospective cohort study of participants in the
      ARIC study who did not have diagnosed diabetes and who attended visit 2 (1990-92;
      n=10 844) and who attended visit 4 (1996-98; n=7194). ARIC participants were
      enrolled from four communities across the USA. Fasting glucose concentration and
      HbA1c were measured at visit 2 and fasting glucose concentration and 2 h glucose
      concentration were measured at visit 4. We compared prediabetes definitions based
      on fasting glucose concentration (American Diabetes Association [ADA] fasting
      glucose concentration cutoff 5.6-6.9 mmol/L and WHO fasting glucose concentration
      cutoff 6.1-6.9 mmol/L), HbA1c (ADA HbA1c cutoff 5.7-6.4% [39-46 mmol/mol] and
      International Expert Committee [IEC] HbA1c cutoff 6.0-6.4% [42-46 mmol/mol]), and
      2 h glucose concentration (ADA and WHO 2 h glucose concentration cutoff 7.8-11.0
      mmol/L). FINDINGS: Prediabetes defined using the ADA fasting glucose
      concentration cutoff (prevalence 4112 [38%] of 10 844 people; 95% CI 37.0-38.8)
      was the most sensitive for major clinical outcomes, whereas using the ADA HbA1c
      cutoff (2027 [19%] of 10 884 people; 18.0-19.4) and IEC HbA1c cutoff (970 [9%] of
      10 844 people; 8.4-9.5), and the WHO fasting glucose concentration cutoff (1213
      [11%] of 10 844 people; 10.6-11.8) were more specific. After demographic
      adjustment, HbA1c-based definitions of prediabetes had higher hazard ratios and
      better risk discrimination for chronic kidney disease, cardiovascular disease,
      peripheral arterial disease, and all-cause mortality than did fasting glucose
      concentration-based definitions (all p<0.05). The C-statistic for incident
      chronic kidney disease was 0.636 for ADA fasting glucose concentration clinical
      categories and 0.640 for ADA HbA1c clinical categories (difference -0.005, 95% CI
      -0.008 to -0.001). The C-statistics were 0.662 for ADA fasting glucose clinical
      concentration categories and 0.672 for ADA HbA1c clinical categories for
      atherosclerotic cardiovascular disease, 0.701 for ADA fasting glucose
      concentration clinical categories and 0.722 for ADA HbA1c clinical categories for
      peripheral arterial disease, and 0.683 for ADA fasting glucose concentration
      clinical categories and 0.688 for ADA HbA1c clinical categories for all-cause
      mortality. Prediabetes defined using the ADA HbA1c cutoff showed a significant
      overall improvement in the net reclassification index for cardiovascular outcomes
      and death compared with prediabetes defined with glucose-based definitions. ADA
      fasting glucose concentration clinical categories, WHO fasting glucose
      concentration clinical categories, and ADA and WHO 2 h glucose concentrations
      clinical categories were not significantly different in terms of risk
      discrimination for chronic kidney disease, cardiovascular outcomes, or mortality
      outcomes. INTERPRETATION: Our results suggest that prediabetes definitions using
      HbA1c were more specific and provided modest improvements in risk discrimination
      for clinical complications. The definition of prediabetes using the ADA fasting
      glucose concentration cutoff was more sensitive overall. FUNDING: US National
      Institutes of Health.

PMID- 27863983
TI  - Professor Alexander T. Florence: An exceptional scientist and man.

PMID- 27863981
TI  - Physicians' Perceived Roles, as Well as Barriers, Toward Caring for Women Sex
      Assault Survivors.
AB  - BACKGROUND: Sexual assault (SA) affects about 40% of women in the United States
      and has many mental and physical health sequelae. Physicians often do not address
      SA with patients, although SA survivors describe a desire to talk to physicians
      to obtain additional help. Little information exists on how providers perceive
      their roles regarding caring for women SA survivors and what barriers they face
      in providing this care. METHODS: We performed a qualitative study using
      semistructured one-on-one interviews with 16 faculty physicians from five
      specialties: obstetrics and gynecology (n = 4), internal medicine (n = 4), family
      medicine (n = 1), emergency medicine (n = 3), and psychiatry (n = 4). Interviews
      were conducted between July 2011 and July 2012, transcribed verbatim, and coded
      using a constant comparative approach. Once a final coding scheme was applied to
      all transcripts, we identified patterns and themes related to perceived roles and
      barriers to caring for SA survivors. RESULTS: Physicians described two main
      categories of roles: clinical tasks (e.g., testing and treating for sexually
      transmitted infections, managing associated mental health sequelae) and
      interpersonal roles (e.g., providing support, acting as patient advocate).
      Physician barriers fell into three main categories: 1) internal barriers (e.g.,
      discomfort with the topic of SA), 2) physician-patient communication, and 3)
      system obstacles (e.g., competing priorities for time). CONCLUSIONS: Although
      physicians describe key roles in caring for SA survivors, several barriers hinder
      their ability to fulfill these roles. Training interventions are needed to reduce
      the barriers that would ultimately improve clinical care for SA survivors.

PMID- 27863984
TI  - Pharmacy preparations: Back in the limelight? Pharmacists make up your mind!
AB  - In this contribution to the theme issue recognizing prof. Florence's achievements
      as editor -in-chief of the Int. J. Pharmaceutics, we analyze the future of
      pharmacy preparations (also known as extemporaneous preparations or compounded
      products). Pharmacy preparations, long considered as an endangered part of the
      pharmacy profession on its way to extinction, may be at the brink of a revival.
      Drivers of this revival are a set of changes related to new clinical concepts and
      supply shortages. Moreover, new production and IT paradigms are being developed
      that facilitate the preparation processes and provide the necessary quality
      management systems. Finally, more detailed legislation (EU) and guidelines (US)
      gets a better hold on preparation in pharmacies. The question is now: is the
      pharmacy profession willing to accept preparation of high quality medicines in
      the pharmacy as an integral part of its professional tasks? If so, institutions
      for pharmacy education should provide the required competences to the pharmacy
      student. If not, alternative scenarios with other disciplines taking the lead
      should be considered. Whatever the choice made, the 'Physicochemical principles
      of pharmacy: in manufacture, formulation and clinical use' by Florence and
      Attwood (2016); will be on the engineer/pharmacy student's desk.

PMID- 27863985
TI  - High systemic availability of core-crosslinked polymeric micelles after
      subcutaneous administration.
AB  - Covalent entrapment of drug molecules within core-crosslinked polymeric micelles
      (CCPM) represents an attractive approach to improve their therapeutic index. As
      an alternative to the most commonly employed intravenous (i.v.) route,
      subcutaneous (s.c.) administration offers the possibility of self-administration
      and thereby may reduce healthcare costs. The aim of this work was to assess the
      pharmacokinetic profile and systemic availability of drug-containing CCPM
      following s.c. injection. We here derivatised dexamethasone (DMS) with three
      different linkers, which enabled covalent attachment of this drug to the core of
      CCPM. The obtained DMS-containing CCPM exhibited varying drug release kinetics in
      vitro. Remarkably, a single dose of DMS-containing CCPM resulted in high systemic
      availability of about 30% following s.c. injection into the flank of healthy
      mice, as evidenced by an AUC between 26-37% relative to the AUC attained
      following i.v. injection. Although different linkers resulted in moderate
      variations in pharmacokinetic parameters, the overall pharmacokinetic profiles of
      these i.v. or s.c. administered nanomedicines were not substantially different.
      Next to DMS, we covalently attached paclitaxel (PTX) to the core of CCPM.
      Similarly, a single s.c. dose of PTX-containing CCPM resulted in high systemic
      availability of about 40% compared to i.v. injection and PTX (entrapped plus
      released) was detected in the blood for at least 3days. Importantly, the systemic
      availability of s.c. administered drug-containing CCPM is substantially higher
      than that of other nanoformulations as reported in the literature (e.g. 3% in
      rodents). These results demonstrate that s.c. administration is a promising route
      to attain high systemic availability of CCPM, enabling a potentially more patient
      friendly and cost-effective treatment approach than the i.v. route.

PMID- 27863982
TI  - Predictors of Breast Cancer Worry in a Hispanic and Predominantly Immigrant
      Mammography Screening Population.
AB  - OBJECTIVE: Worry about developing breast cancer (BC) has been associated with
      participation in screening and genetic testing and with follow-up of abnormal
      screening results. Little is known about the scope and predictors of BC worry in
      Hispanic and immigrant populations. METHODS: We collected in-person interview
      data from 250 self-identified Hispanic women recruited from an urban mammography
      facility (average age 50.4 years; 82% foreign-born). Women reported whether they
      worried about developing breast cancer rarely/never (low worry), sometimes
      (moderate worry), or often/all the time (high worry). We examined whether
      sociocultural and psychological factors (e.g., acculturation, education,
      perceived risk), and risk factors and objective risk for BC (e.g., family
      history, Gail model 5-year risk estimates, parity) predicted BC worry using
      multinomial and logistic regression. RESULTS: In multivariable models, women who
      perceived higher absolute BC risk (odds ratio, 1.66 [95% confidence interval,
      1.28-2.14] for a one-unit increase in perceived lifetime risk) and comparative BC
      risk (e.g., odds ratio, 2.73, 95% confidence interval, 1.23-6.06) were more
      likely to report high BC worry than moderate or low BC worry. There were no
      associations between BC worry and indicators of objective risk or acculturation.
      CONCLUSIONS: In Hispanic women undergoing screening mammography, higher
      perceptions of BC risk, in both absolute and comparative terms, were associated
      independently with high BC worry, and were stronger predictors of BC worry than
      indicators of objective BC risk, including family history, mammographic density,
      and personal BC risk estimates.

PMID- 27863986
TI  - Microfluidics based manufacture of liposomes simultaneously entrapping
      hydrophilic and lipophilic drugs.
AB  - Despite the substantial body of research investigating the use of liposomes,
      niosomes and other bilayer vesicles for drug delivery, the translation of these
      systems into licensed products remains limited. Indeed, recent shortages in the
      supply of liposomal products demonstrate the need for new scalable production
      methods for liposomes. Therefore, the aim of our research has been to consider
      the application of microfluidics in the manufacture of liposomes containing
      either or both a water soluble and a lipid soluble drug to promote co-delivery of
      drugs. For the first time, we demonstrate the entrapment of a hydrophilic and a
      lipophilic drug (metformin and glipizide respectively) both individually, and in
      combination, using a scalable microfluidics manufacturing system. In terms of the
      operating parameters, the choice of solvents, lipid concentration and
      aqueous:solvent ratio all impact on liposome size with vesicle diameter ranging
      from ~90 to 300nm. In terms of drug loading, microfluidics production promoted
      high loading within ~100nm vesicles for both the water soluble drug (20-25% of
      initial amount added) and the bilayer embedded drug (40-42% of initial amount
      added) with co-loading of the drugs making no impact on entrapment efficacy.
      However, co-loading of glipizide and metformin within the same liposome
      formulation did impact on the drug release profiles; in both instances the
      presence of both drugs in the one formulation promoted faster (up to 2 fold)
      release compared to liposomes containing a single drug alone. Overall, these
      results demonstrate the application of microfluidics to prepare liposomal systems
      incorporating either or both an aqueous soluble drug and a bilayer loaded drug.

PMID- 27863987
TI  - Optimized synthesis and crystalline stability of gamma-cyclodextrin metal-organic
      frameworks for drug adsorption.
AB  - The biocompatible and renewable cyclodextrin metal-organic frameworks (CD-MOFs)
      have addressed a range of opportunities in molecular storage and separation
      sciences. The reported protocols for their synthesis, however, were carried out
      at room temperature over long time periods of time (24h), producing crystals of
      relatively poor uniformity. In this investigation, micron sized gamma-CD-MOFs
      were synthesized by an optimized vapor diffusion method at elevated temperature
      (50 degrees C) within 6h, after which the size control, crystalline stability and
      drug adsorption behavior were investigated in detail. In this manner, uniform
      cubic gamma-CD-MOF crystals were obtained when the reaction temperature was
      raised to 50 degrees C with pre-addition of the reaction solvent. The size of
      gamma-CD-MOFs was adjusted efficiently by changing the reactant concentrations,
      temperatures, time, gamma-CD ratios to KOH and surfactant concentrations, without
      influencing the porosity and crystallinity of the material markedly. Varing
      degrees of reduction in crystallinity and change in morphology were observed when
      the gamma-CD-MOF crystals are treated under conditions of high temperature (100
      degrees C), high humidity (92.5%) and polar solvents (e.g., MeOH and DMF). In
      relation to drug adsorption by gamma-CD-MOFs, most of the drug molecules
      containing carboxyl groups showed relatively high adsorption (>5%), while low
      adsorption (<5%) was found for drugs with nitrogen-containing heterocyclic rings.
      In addition, the adsorption kinetics of captopril to standard gamma-CD-MOFs
      matched a pseudo-second-order model rather well, whilst captopril adsorption to
      the damaged gamma-CD-MOFs only partially matched the pseudo-second-order model.
      In summary, based upon the optimized synthesis and size control of gamma-CD-MOFs,
      the crystalline stability and drug adsorption characteristics of gamma-CD-MOF
      crystals have been evaluated as a fundamental requirement of a potential vehicle
      for drug delivery.

PMID- 27863988
TI  - Ibuprofen delivery into and through the skin from novel oxidized cellulose-based
      gels and conventional topical formulations.
AB  - The delivery of ibuprofen into and through the skin from novel formulations
      containing TEMPO-oxidized cellulose nanofibril-based (TOCN) gels was compared to
      that from two conventional and commercially available products. The gels were
      evaluated in-vitro (using both silicone membranes, and pig skin) and in-vivo in
      human volunteers. All gels showed consistent behaviour in a standard in vitro
      release test. The stratum corneum (SC) uptake and skin penetration of ibuprofen
      in vitro from the novel gels and the marketed formulations were generally
      comparable even though the drug loading in the TOCN-based vehicles was only 20%
      of that in the 'reference' products. In vivo, the new gels appeared to enhance
      drug uptake into the SC following a relatively short application time, again
      matching the performance of the commercial formulations. Taken together, the
      results of this research provide proof-of-concept for the idea that the
      sustainable, oxidized cellulose gels may provide more efficient drug delivery
      into and through the skin, thereby improving drug utilisation and reducing
      potential adverse effects when such formulations are applied chronically over
      large skin areas.

PMID- 27863989
TI  - The gut in the beaker: Missing the surfactants?
AB  - Gastrointestinal drug administration is the preferred route for the majority of
      drugs however, the natural physiology and physicochemistry of the
      gastrointestinal tract is critical to absorption but complex and influenced by
      factors such as diet or disease. The pharmaceutical sciences drive for product
      consistency has led to the development of in vitro product performance tests
      whose utility and interpretation is hindered by the complexity, variability and a
      lack of understanding. This article explores some of these issues with respect to
      the drug, formulation and the presence of surfactant excipients and how these
      interact with the natural bile salt surfactants. Interactions start in the mouth
      and during swallowing but the stomach and small intestine present the major
      challenges related to drug dissolution, solubility, the impact of surfactants and
      supersaturation along with precipitation. The behaviour of lipid based
      formulations and the influence of surfactant excipients is explored along with
      the difficulties of translating in vitro results to in vivo performance. Possible
      future research areas are highlighted with the conclusion that, "a great deal of
      work using modern methods is still required to clarify the situation".

PMID- 27863991
TI  - Applicability of the modified CHA2DS2-VASc score for stroke risk stratification
      in Caucasian atrial fibrillation patients.

PMID- 27863990
TI  - Cytochrome P450 enzymes but not NADPH oxidases are the source of the NADPH
      dependent lucigenin chemiluminescence in membrane assays.
AB  - : Measuring NADPH oxidase (Nox)-derived reactive oxygen species (ROS) in living
      tissues and cells is a constant challenge. All probes available display
      limitations regarding sensitivity, specificity or demand highly specialized
      detection techniques. In search for a presumably easy, versatile, sensitive and
      specific technique, numerous studies have used NADPH-stimulated assays in
      membrane fractions which have been suggested to reflect Nox activity. However, we
      previously found an unaltered activity with these assays in triple Nox knockout
      mouse (Nox1-Nox2-Nox4-/-) tissue and cells compared to wild type. Moreover, the
      high ROS production of intact cells overexpressing Nox enzymes could not be
      recapitulated in NADPH-stimulated membrane assays. Thus, the signal obtained in
      these assays has to derive from a source other than NADPH oxidases. Using a
      combination of native protein electrophoresis, NADPH-stimulated assays and mass
      spectrometry, mitochondrial proteins and cytochrome P450 were identified as
      possible source of the assay signal. Cells lacking functional mitochondrial
      complexes, however, displayed a normal activity in NADPH-stimulated membrane
      assays suggesting that mitochondrial oxidoreductases are unlikely sources of the
      signal. Microsomes overexpressing P450 reductase, cytochromes b5 and P450
      generated a NADPH-dependent signal in assays utilizing lucigenin, L-012 and
      dihydroethidium (DHE). Knockout of the cytochrome P450 reductase by CRISPR/Cas9
      technology (POR-/-) in HEK293 cells overexpressing Nox4 or Nox5 did not interfere
      with ROS production in intact cells. However, POR-/- abolished the signal in
      NADPH-stimulated assays using membrane fractions from the very same cells.
      Moreover, membranes of rat smooth muscle cells treated with angiotensin II showed
      an increased NADPH-dependent signal with lucigenin which was abolished by the
      knockout of POR but not by knockout of p22phox. IN CONCLUSION: the cytochrome
      P450 system accounts for the majority of the signal of Nox activity
      chemiluminescence based assays.

PMID- 27863992
TI  - Delirium: Time to climb this babylon tower.

PMID- 27863993
TI  - Association between Micronutrients Intake/Status and Carotid Intima Media
      Thickness: A Systematic Review.
AB  - BACKGROUND: Carotid intima media thickness (IMT) is a noninvasive marker of the
      extent and severity of subclinical atherosclerosis. Micronutrient intake may
      affect atherosclerosis and play a major role in the development of cardiovascular
      diseases (CVDs). OBJECTIVE: The primary aim of this review was to synthesize the
      evidence regarding the association between carotid IMT and selected
      micronutrients. METHOD: The authors searched PubMed, Cochrane, and EMBASE
      databases from inception to June 2016 for selected micronutrients, CVD, carotid
      IMT, and antioxidants. Thirty-five original studies met the inclusion criteria
      and were reviewed following preferred reporting items for systematic review and
      meta-analysis guidelines. RESULTS: Although not all studies found consistent
      results, the weight of the evidence suggests that high intakes and/or circulatory
      levels of magnesium, as well as vitamin D and the vitamin B group, may be
      associated with lower carotid IMT or reduced progression of carotid IMT. The
      majority of studies did not find any significant association between vitamin E
      and C and carotid IMT. Less evidence was available for associations of retinol,
      zinc, and iron with carotid IMT. CONCLUSIONS: In general, the current evidence
      concerning micronutrient intake and carotid IMT is largely inconclusive.
      Pragmatic clinical trials are required to determine whether dietary or
      supplemental intake of specific micronutrients alters carotid IMT, which is a
      surrogate measure of cardiovascular risk.

PMID- 27863994
TI  - Understanding the Physics of Functional Fibers in the Gastrointestinal Tract: An
      Evidence-Based Approach to Resolving Enduring Misconceptions about Insoluble and
      Soluble Fiber.
AB  - Enduring misconceptions about the physical effects of fiber in the gut have led
      to misunderstandings about the health benefits attributable to insoluble and
      soluble fiber. This review will focus on isolated functional fibers (eg, fiber
      supplements) whose effects on clinical outcomes have been readily assessed in
      well-controlled clinical studies. This review will also focus on three health
      benefits (cholesterol lowering, improved glycemic control, and normalizing stool
      form [constipation and diarrhea]) for which reproducible evidence of clinical
      efficacy has been published. In the small bowel, clinically meaningful health
      benefits (eg, cholesterol lowering and improved glycemic control) are highly
      correlated with the viscosity of soluble fibers: high viscosity fibers (eg, gel
      forming fibers such as b-glucan, psyllium, and raw guar gum) exhibit a
      significant effect on cholesterol lowering and improved glycemic control, whereas
      nonviscous soluble fibers (eg, inulin, fructooligosaccharides, and wheat dextrin)
      and insoluble fibers (eg, wheat bran) do not provide these viscosity-dependent
      health benefits. In the large bowel, there are only two mechanisms that drive a
      laxative effect: large/coarse insoluble fiber particles (eg, wheat bran)
      mechanically irritate the gut mucosa stimulating water and mucous secretion, and
      the high water-holding capacity of gel-forming soluble fiber (eg, psyllium)
      resists dehydration. Both mechanisms require that the fiber resist fermentation
      and remain relatively intact throughout the large bowel (ie, the fiber must be
      present in stool), and both mechanisms lead to increased stool water content,
      resulting in bulky/soft/easy-to-pass stools. Soluble fermentable fibers (eg,
      inulin, fructooligosaccharide, and wheat dextrin) do not provide a laxative
      effect, and some fibers can be constipating (eg, wheat dextrin and fine/smooth
      insoluble wheat bran particles). When making recommendations for a fiber
      supplement, it is essential to recognize which fibers possess the physical
      characteristics required to provide a beneficial health effect, and which fiber
      supplements are supported by reproducible, rigorous evidence of one or more
      clinically meaningful health benefits.

PMID- 27863996
TI  - Interventions to improve adherence to antiretroviral therapy: a systematic review
      and network meta-analysis.
AB  - BACKGROUND: High adherence to antiretroviral therapy is crucial to the success of
      HIV treatment. We evaluated comparative effectiveness of adherence interventions
      with the aim of informing the WHO's global guidance on interventions to increase
      adherence. METHODS: For this systematic review and network meta-analysis, we
      searched for randomised controlled trials of interventions that aimed to improve
      adherence to antiretroviral therapy regimens in populations with HIV. We searched
      Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for reports
      published up to July 16, 2015, and searched major conference abstracts from Jan
      1, 2013, to July 16, 2015. We extracted data from eligible studies for study
      characteristics, interventions, patients' characteristics at baseline, and
      outcomes for the study populations of interest. We used network meta-analyses to
      compare adherence and viral suppression for all study settings (global network)
      and for studies in low-income and middle-income countries only (LMIC network).
      FINDINGS: We obtained data from 85 trials with 16 271 participants. Short message
      service (SMS; text message) interventions were superior to standard of care in
      improving adherence in both the global network (odds ratio [OR] 1.48, 95%
      credible interval [CrI] 1.00-2.16) and in the LMIC network (1.49, 1.04-2.09).
      Multiple interventions showed generally superior adherence to single
      interventions, indicating additive effects. For viral suppression, only cognitive
      behavioural therapy (1.46, 1.05-2.12) and supporter interventions (1.28, 1.01
      1.71) were superior to standard of care in the global network; none of the
      interventions improved viral response in the LMIC network. For the global
      network, the time discrepancy (whether the study outcome was measured during or
      after intervention was withdrawn) was an effect modifier for both adherence to
      antiretroviral therapy (coefficient estimate -0.43, 95% CrI -0.75 to -0.11) and
      viral suppression (-0.48; -0.84 to -0.12), suggesting that the effects of
      interventions wane over time. INTERPRETATION: Several interventions can improve
      adherence and viral suppression; generally, their estimated effects were modest
      and waned over time. FUNDING: WHO.

PMID- 27863997
TI  - A link between antiretrovirals and perinatal outcomes?

PMID- 27863995
TI  - Tumor-targeted delivery of sunitinib base enhances vaccine therapy for advanced
      melanoma by remodeling the tumor microenvironment.
AB  - Development of an effective treatment against advanced tumors remains a major
      challenge for cancer immunotherapy. We have previously developed a potent mannose
      modified lipid calcium phosphate (LCP) nanoparticle (NP)-based Trp2 vaccine for
      melanoma therapy, but because this vaccine can induce a potent anti-tumor immune
      response only during the early stages of melanoma, poor tumor growth inhibition
      has been observed in more advanced melanoma models, likely due to the development
      of an immune-suppressive tumor microenvironment (TME). To effectively treat this
      aggressive tumor, a multi-target receptor tyrosine kinase inhibitor, sunitinib
      base, was efficiently encapsulated into a targeted polymeric micelle nano
      delivery system (SUNb-PM), working in a synergistic manner with vaccine therapy
      in an advanced mouse melanoma model. SUNb-PM not only increased cytotoxic T-cell
      infiltration and decreased the number and percentage of MDSCs and Tregs in the
      TME, but also induced a shift in cytokine expression from Th2 to Th1 type while
      remodeling the tumor-associated fibroblasts, collagen, and blood vessels in the
      tumor. Additionally, inhibition of the Stat3 and AKT signaling pathways by SUNb
      PM may induce tumor cell apoptosis or decrease tumor immune evasion. Our findings
      indicated that targeted delivery of a tyrosine kinase inhibitor to tumors can be
      used in a novel synergistic way to enhance the therapeutic efficacy of existing
      immune-based therapies for advanced melanoma.

PMID- 27863999
TI  - Assessing progress with HIV incidence in national cohorts.

PMID- 27863998
TI  - Swaziland HIV Incidence Measurement Survey (SHIMS): a prospective national cohort
      study.
AB  - BACKGROUND: Swaziland has the highest national HIV prevalence worldwide. The
      Swaziland HIV Incidence Measurement Survey (SHIMS) provides the first national
      HIV incidence estimate based on prospectively observed HIV seroconversions.
      METHODS: A two-stage survey sampling design was used to select a nationally
      representative sample of men and women aged 18-49 years from 14 891 households in
      575 enumeration areas in Swaziland, who underwent household-based counselling and
      rapid HIV testing during 2011. All individuals aged 18-49 years who resided or
      had slept in the household the night before and were willing to undergo home
      based HIV testing, answer demographic and behavioural questions in English or
      siSwati, and provide written informed consent were eligible for the study. We
      performed rapid HIV testing and assessed sociodemographic and behavioural
      characteristics with use of a questionnaire at baseline and, for HIV-seronegative
      individuals, 6 months later. We calculated HIV incidence with Poisson regression
      modelling as events per person-years * 100, and we assessed covariables as
      predictors with Cox proportional hazards modelling. Survey weighting was applied
      and all models used survey sampling methods. FINDINGS: Between Dec 10, 2010, and
      June 25, 2011, 11 897 HIV-seronegative adults were enrolled in SHIMS and 11 232
      (94%) were re-tested. Of these, 145 HIV seroconversions were observed, resulting
      in a weighted HIV incidence of 2.4% (95% CI 2.1-2.8). Incidence was nearly twice
      as high in women (3.1%; 95% CI 2.6-3.7) as in men (1.7%; 1.3-2.1, p<0.0001).
      Among men, partner's HIV-positive status (adjusted hazard ratio [aHR] 2.67, 1.06
      6.82, p=0.040) or unknown serostatus (aHR 4.64, 2.32-9.27, p<0.0001) in the past
      6 months predicted HIV seroconversion. Among women, significant predictors
      included not being married (aHR 2.90, 1.44-5.84, p=0.0030), having a spouse who
      lives elsewhere (aHR 2.66, 1.29-5.45, p=0.0078), and having a partner in the past
      6 months with unknown HIV status (aHR 2.87, 1.44-5.84, p=0.0030). INTERPRETATION:
      Swaziland has the highest national HIV incidence in the world. In high-prevalence
      countries, population-based incidence measures and programmes that further expand
      HIV testing and support disclosure of HIV status are needed. FUNDING: President's
      Emergency Plan for AIDS Relief (PEPFAR) by the Centers for Disease Control and
      Prevention.

PMID- 27864000
TI  - Timing of initiation of antiretroviral therapy and adverse pregnancy outcomes: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Although lifelong combination antiretroviral therapy (ART) is
      recommended for all individuals with HIV, few data exist for pregnancy outcomes
      associated with ART initiation before conception. We assessed adverse pregnancy
      outcomes associated with ART initiated before conception compared with that of
      ART started after conception. METHODS: We did a systematic review of studies from
      low-income, middle-income, and high-income countries by searching the Cochrane
      Central Register of Controlled Trials, Embase, LILACS, MEDLINE, Toxline, Web of
      Knowledge, and WHO Global Index Medicus and trials in progress (International
      Clinical Trials Registry Platform) for randomised trials, quasi-randomised
      trials, and prospective cohort studies done between Jan 1, 1980, and June 1,
      2016, in which timing of ART initiation in pregnant women living with HIV was
      reported. We used the risk ratio (RR) and corresponding 95% CIs as the primary
      measure to assess the association between the selected outcomes and ART
      initiation before conception versus after conception. We used a random-effects
      model to pool risk ratios. FINDINGS: We included 11 studies with 19 189 mother
      infant pairs. Women who started ART before conception were significantly more
      likely to deliver preterm (pooled RR 1.20, 95% CI 1.01-1.44) or very preterm
      (1.53, 1.22-1.92), or to have low-birthweight infants (1.30, 1.04-1.62) than were
      those who began ART after conception. Few data exist for neonatal mortality. The
      risk of very low birthweight, small for gestational age, severe small for
      gestational age, stillbirth, and congenital anomalies did not differ
      significantly between women who were taking ART before conception and those who
      began ART after conception. INTERPRETATION: The benefits of ART for maternal
      health and prevention of perinatal transmission outweigh risks, but data for the
      extent and severity of these risks are scarce and of low quality. As use of ART
      before conception rapidly increases globally, monitoring for potential adverse
      pregnancy outcomes will be crucial. FUNDING: WHO.

PMID- 27864001
TI  - Actionable adherence monitoring to optimise intervention.

PMID- 27864002
TI  - Gamma-tocotrienol reverses multidrug resistance of breast cancer cells with a
      mechanism distinct from that of atorvastatin.
AB  - In addition to its antioxidant properties, gamma-tocotrienol also has the ability
      to inhibit HMG-CoA reductase, which is the key enzyme in the mevalonate pathway
      for cholesterol biosynthesis. Statins, the competitive inhibitors of HMG-CoA
      reductase, display potent anticancer activity and reversal ability of multidrug
      resistance in a variety of tumor cells, which is believed to be due to their
      inhibition of HMG-CoA reductase. Here, we determined the role of the mevalonate
      pathway in gamma-tocotrienol-mediated reversal of multidrug resistance in cancer
      cells. We found both gamma-tocotrienol and atorvastatin effectively reversed
      multidrug resistance of MCF-7/Adr and markedly inhibited the intracellular levels
      of FPP and GGPP. Exogenous addition of mevalonate or FPP and GGPP almost
      completely prevented the reversal ability of atorvastatin but only partly
      attenuated the reversal effect of gamma-tocotrienol on doxorubicin resistance. In
      addition, gamma-tocotrienol actively inhibited the expression of P-gp and
      increased the accumulation of doxorubicin in cells, which led to the enhanced
      G2/M arrest and cell apoptosis. Taken together, gamma-tocotrienol reversed the
      multidrug resistance of MCF-7/Adr with a mechanism distinct from that of
      atorvastatin. Instead of the mevalonate pathway, the inhibition of P-gp
      expression is a potential mechanism by which gamma-tocotrienol reverses multidrug
      resistance in MCF-7/Adr.

PMID- 27864003
TI  - Novel screening system for high-affinity ligand of heredity vitamin D-resistant
      rickets-associated vitamin D receptor mutant R274L using bioluminescent sensor.
AB  - Hereditary vitamin D-resistant rickets (HVDRR) is caused by mutations in the
      vitamin D receptor (VDR) gene. Arg274 located in the ligand binding domain (LBD)
      of VDR is responsible for anchoring 1alpha,25-dihydroxyvitamin D3
      (1alpha,25(OH)2D3) by forming a hydrogen bond with the 1alpha-hydroxyl group of
      1alpha,25(OH)2D3. The Arg274Leu (R274L) mutation identified in patients with
      HVDRR causes a 1000-fold decrease in the affinity for 1alpha,25(OH)2D3, and
      dramatically reduces vitamin D- related gene expression. Recently, we
      successfully constructed fusion proteins consisting of split-luciferase and LBD
      of the VDR. The chimeric protein LucC-LBD-LucN, which displays the C-terminal
      domain of luciferase (LucC) at its N-terminus, can detect and discriminate
      between VDR agonists and antagonists. The LucC-LBD (R274L)-LucN was constructed
      to screen high-affinity ligands for the mutant VDR (R274L). Of the 33 vitamin D
      analogs, 5 showed much higher affinities for the mutant VDR (R274L) than
      1alpha,25(OH)2D3, and 2alpha-[2-(tetrazol-2-yl)ethyl]-1alpha,25-(OH)2D3 showed
      the highest affinity. These compounds might be potential therapeutics for HVDRR
      caused by the mutant VDR (R274L).

PMID- 27864004
TI  - Beta adrenergic blockade and decompensated cirrhosis.
AB  - Non-selective betablockers (NSBBs) remain the cornerstone of medical treatment of
      portal hypertension. The evidence for their efficacy to prevent variceal bleeding
      is derived from prospective trials, which largely excluded patients with
      refractory ascites and renal failure. In parallel to the increasing knowledge on
      portal hypertension-induced changes in systemic hemodynamics, cardiac function,
      and renal perfusion, emerging studies have raised concerns about harmful effects
      of NSBBs. Clinicians are facing an ongoing controversy on the use of NSBBs in
      patients with advanced cirrhosis. On the one hand, NSBBs are effective in
      preventing variceal bleeding and might also have beneficial non-hemodynamic
      effects, however, they also potentially induce hypotension and limit the cardiac
      reserve. An individualized NSBB regimen tailored to the specific
      pathophysiological stage of cirrhosis might optimize patient management at this
      point. This article aims to give practical recommendations on the use of NSBBs in
      patients with decompensated cirrhosis.

PMID- 27864005
TI  - Changes in DTI parameters in the optic tracts of macaque monkeys with monocular
      blindness.
AB  - For humans and non-human primates, the alteration of the visual pathway's white
      matter fibers after visual deprivation has been partially explored. However, the
      changes in the optic tracts after the transection of the optic nerve have not
      been well characterized. In the current study, we attempted to investigate the
      differences in optic tracts between normal and unilateral optic nerve transected
      macaque monkeys using diffusion tensor imaging (DTI). Four healthy neonatal
      macaque monkeys were randomly divided into 2 groups, with 2 in each group. Group
      A served as a control group, and Group B underwent unilateral (right eye) optic
      nerve transection to produce monocular blindness. Sixteen months (Group B16M) and
      thirty-two months (Group B32M) after optic nerve transection, diffusion tensor
      imaging was performed on all monkeys. Then, we compared fractional anisotropy
      (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD)
      in bilateral optic tracts between Group A and Group B and between Group B16M and
      Group B32M. In both Group B16M and Group B32M, when compared with normal monkeys
      in Group A, FA was decreased and MD, AD and RD were increased in the bilateral
      optic tracts of monkeys with monocular blindness. Furthermore, compared with
      Group B16M, FA was reduced and MD, AD, RD were more obviously increased in the
      bilateral optic tracts of Group B32M, and noticeable differences in MD, AD and RD
      were found between the left and right optic tracts in group B32M. We believe that
      the results of this study would be helpful in investigation of the histological
      abnormalities of the integrity damage, axonal degeneration and demyelination of
      optic tracts in macaque monkeys with monocular blindness by DTI parameters in
      noninvasively and quantitatively.

PMID- 27864006
TI  - Corrections.

PMID- 27864007
TI  - Six generations of epidermolytic palmoplantar keratoderma, associated with a KRT9
      R163W mutation.
AB  - Epidermolytic palmoplantar keratoderma (EPPK) is a rare autosomal dominant skin
      disorder characterized by diffuse hyperkeratosis on the palms and soles. Whole
      exome sequencing (WES) has become a powerful tool for the detection of rare
      causal variants of Mendelian disorders. However, no causal gene for EPPK in the
      Uygur population has been identified until now, and no treatment exists than can
      address the underlying pathology.WES analysis was undertaken on two individuals
      from a large Uygur EPPK pedigree whose disease locus mapped to 17q21.2
      (chr:38994621-39893408) following previous linkage analysis. KRT9
      (NM_000226.3:c.487C>T, p.Arg163Trp), and KRT15 (XM_005257346.1:c.212G>T,
      XP_005257403.1:p.Gly71Val) located in this region, have been identified as two
      candidate causative genes for EPPK in the Uygur family. Sanger sequencing was
      conducted on this region in other affected individuals (n = 38) from this family,
      non-affected individuals (n = 56) from this family and 100 unrelated controls.
      The missense mutation KRT9 c.487C>T, identified in this large Uygur population,
      is a potential causative mutation. To date, EPPK has no effective therapy, and
      siRNA is a potential avenue for EPPK therapy. To investigate this, full-length
      wild-type Keratin9 (KRT9; pKRT9-WT) and p.Arg163Trp (pKRT9-R163W) were then
      transfected into HaCaT cells. The small interfering RNAs targeting the KRT9 R163W
      mutant and wildtype KRT9 were transfected into HaCaT cells, and total RNA
      isolated at 72 h post-transfection. Quantitative polymerase chain reaction and
      western blotting were used to analyse the effects of knock-down on KRT9 mRNA and
      protein levels, respectively. siRNA was shown to specifically inhibit mutant KRT9
      mRNA and protein expression (p < 0.01, with 95% confidence limits). Our study
      suggests that KRT9 is a causal gene for EPPK. This information is helpful for
      understanding the pathogenesis of EPPK in the Uygur population and raises the
      possibility of designing a novel siRNA treatment strategy for this population of
      EPPK patients.

PMID- 27864009
TI  - Evolutionary dynamics of triosephosphate isomerase gene intron location pattern
      in Metazoa: A new perspective on intron evolution in animals.
AB  - Intron evolution, including its dynamics in the evolutionary transitions and
      diversification of eukaryotes, remains elusive. Inadequate taxon sampling due to
      data shortage, unclear phylogenetic framework, and inappropriate outgroup
      application might be among the causes. Besides, the integrity of all the introns
      within a gene was often neglected previously. Taking advantage of the ancient
      conserved triosephosphate isomerase gene (tim), the relatively robust phylogeny
      of Metazoa, and choanoflagellates as outgroup, the evolutionary dynamics of tim
      intron location pattern (ILP) in Metazoa was investigated. From 133
      representative species of ten phyla, 30 types of ILPs were identified. A most
      common one, which harbors the maximum six intron positions, is deduced to be the
      common ancestral tim ILP of Metazoa, which almost had formed in their protozoan
      ancestor and was surprisingly retained and passed down till to each ancestors of
      metazoan phyla. In the subsequent animal diversification, it underwent different
      evolutionary trajectories: within Deuterostomia, it was almost completely
      retained only with changes in a few species with relatively recently fast
      evolving histories, while within the rapidly radiating Protostomia, besides few
      but remarkable retention, it usually displayed extensive intron losses and a few
      gains. Therefore, a common ancestral exon-intron arrangement pattern of an animal
      gene is definitely discovered; besides the 'intron-rich view' of early animal
      genes being confirmed, the novel insight that high exon-intron re-arrangements of
      genes seem to be associated with the relatively recently rapid evolution of
      lineages/species/genomes but have no correlation with the ancient major
      evolutionary transitions in animal evolution, is revealed.

PMID- 27864008
TI  - Renal plasma flow (RPF) measured with multiple-inversion-time arterial spin
      labeling (ASL) and tracer kinetic analysis: Validation against a dynamic contrast
      enhancement method.
AB  - PURPOSE: To propose and validate a method for accurately quantifying renal plasma
      flow (RPF) with arterial spin labeling (ASL). MATERIALS AND METHODS: The proposed
      method employs a tracer-kinetic approach and derives perfusion from the slope of
      the ASL difference signal sampled at multiple inversion-times (TIs). To validate
      the method's accuracy, we performed a HIPAA-compliant and IRB-approved study with
      15 subjects (9 male, 6 female; age range 24-73) to compare RPF estimates obtained
      from ASL to those from a more established dynamic contrast-enhanced (DCE) MRI
      method. We also investigated the impact of TI-sampling density on the accuracy of
      estimated RPF. RESULTS: Good agreement was found between ASL- and DCE-measured
      RPF, with a mean difference of 9+/-30ml/min and a correlation coefficient R=0.92
      when ASL signals were acquired at 16 TIs and a mean difference of 9+/-57ml/min
      and R=0.81 when ASL signals were acquired at 5 TIs. RPF estimated from ASL
      signals acquired at only 2 TIs (400 and 1200ms) showed a low correlation with DCE
      measured values (R=0.30). CONCLUSION: The proposed ASL method is capable of
      measuring RPF with an accuracy that is comparable to DCE MRI. At least 5 TIs are
      recommended for the ASL acquisition to ensure reliability of RPF measurements.

PMID- 27864010
TI  - Differentially expressed genes in the testicular tissues of adenylyl cyclase 3
      knockout mice.
AB  - Adenylate cyclase 3 (AC3) is an important component of the cyclic adenosine 3',5'
      monophosphate (cAMP) signaling pathway and converts adenosine triphosphate into
      cAMP. Male mice with AC3 deletion (AC3-/-) are sterile. However, the mechanical
      mechanism remains unclear. By TUNEL staining, we found that cell apoptosis in the
      testicular tissues of AC3-/- mice increased significantly compared with that in
      the wild-type (AC3+/+) mice. Differentially expressed genes regulated by AC3 in
      the testicular tissues were identified by gene chip hybridization. We observed
      that the expression of 693 genes was altered in the testicular tissues of AC3-/-
      mice, including 330 up-regulated and 363 down-regulated gene expression with fold
      changes higher than 2 (>=2) as the standards. Furthermore, part of these
      differentially expressed genes was verified by the real-time fluorescence
      quantification PCR and immunofluorescent staining. The expression levels of the
      genes related to olfactory receptors, cell apoptosis, transcriptional activity,
      defensive reaction, cell adhesion, cell death, and immunoreactions were
      significantly altered in the testicular tissues of AC3-/- mice compared with
      AC3+/+ mice. In addition, the corresponding Ca2+, cAMP, and cell adhesion
      signaling pathways, as well as the signaling pathways related to axon guidance
      and cell interaction, were altered significantly in the AC3-/- mice. These data
      would help elucidate the general understanding of the mechanisms underlying the
      sterility in AC3-/- male mice.

PMID- 27864011
TI  - Molecular characterization of Candida isolates from intensive care unit patients,
      Krakow, Poland.
AB  - BACKGROUND: Over the last decades, Candida species have emerged as important
      pathogens in immunocompromised patients. Nosocomial infections are mainly of
      endogenous origin. Nevertheless, some cases of exogenous candidiasis have also
      been reported. AIMS: The aim of this study was to evaluate the genetic
      relatedness between Candida albicans, Candida glabrata, Candida tropicalis,
      Candida krusei and Candida kefyr isolates recovered from intensive care unit
      (ICU) patients. METHODS: A total of 132 Candida clinical isolates (62 C.
      albicans, 40 C. glabrata, 13 C. tropicalis, 11 C. krusei, 6 C. kefyr), obtained
      from specimens of endotracheal aspirate, urine and blood taken from patients of a
      tertiary hospital in Poland, were included in the study. Species identification
      was performed by PCR method and genetic relatedness was assessed by randomly
      amplified polymorphic DNA assay (RAPD) with five primers. RESULTS: The RAPD
      analysis revealed high genetic diversity among the studied Candida isolates,
      indicating that most of the strains were from endogenous sources. Only two clonal
      strains of C. glabrata isolated from different patients were observed, suggesting
      a possible cross-transmission of these pathogens. CONCLUSIONS: Our study
      confirmed the high discriminatory power of the RAPD assay. This genotyping method
      can be applied to local epidemiological studies of Candida species.

PMID- 27864012
TI  - Toolbox of multiple-item measures aligning with the ICF Core Sets for children
      and youth with cerebral palsy.
AB  - Selecting appropriate measure(s) for clinical and/or research applications for
      children and youth with Cerebral Palsy (CP) poses many challenges. The newly
      developed International Classification of Functioning, Disability and Health
      (ICF) Core Sets for children and youth with CP serve as universal guidelines for
      assessment, intervention and follow-up. The aims of this study were: 1) to
      identify valid and reliable measures used in studies with children and youth with
      CP, 2) to characterize the content of each measure using the ICF Core Sets for
      children and youth with CP as a framework, and finally 3) to create a toolbox of
      psychometrically sound measures covering the content of each ICF Core Set for
      children and youth with CP. All clearly defined multiple-item measures used in
      studies with CP between 1998 and 2015 were identified. Psychometric properties
      were extracted when available. Construct of the measures were linked to the ICF
      Core Sets. Overall, 83 multiple-item measures were identified. Of these, 68
      measures (80%) included reliability and validity testing. The majority of the
      measures were discriminative, generic and designed for school-aged children. The
      degree to which measures with proven psychometric properties represented the ICF
      Core Sets for children and youth with CP varied considerably. Finally, 25 valid
      and reliable measures aligned highly with the content of the ICF Core Sets, and
      as such, these measures are proposed as a novel ICF Core Sets-based toolbox of
      measures for CP. Our results will guide professionals seeking appropriate
      measures to meet their research and clinical needs worldwide.

PMID- 27864013
TI  - Factors predictive of response, disease progression, and overall survival after
      dabrafenib and trametinib combination treatment: a pooled analysis of individual
      patient data from randomised trials.
AB  - BACKGROUND: Dabrafenib plus trametinib treatment provides significant benefits
      over BRAF-inhibitor monotherapy in patients with BRAFV600E-mutant or BRAFV600K
      mutant advanced melanoma; however, in many patients the disease progresses,
      leading to death. With many treatment options available, understanding clinical
      factors that predict long-term response and survival for treatments is important
      for optimisation of patient management. We aimed to identify clinical factors
      associated with long-term response and survival using pooled data from randomised
      trials of dabrafenib plus trametinib in patients with metastatic BRAF-mutant
      melanoma. METHODS: We did a retrospective individual data analysis based on all
      published randomised trials that included treatment-naive patients with BRAFV600E
      mutant or BRAFV600K-mutant metastatic melanoma who received the approved dose of
      dabrafenib 150 mg twice daily plus trametinib 2 mg once daily. Data were pooled
      from patients in the BRF113220 (part C; March 26, 2010, to Jan 15, 2015), COMBI-d
      (May 4, 2012, to Jan 12, 2015), and COMBI-v (June 4, 2012, to March 13, 2015)
      randomised trials. Patients with untreated brain metastases were not permitted to
      enrol in these trials. Baseline factors, identified a priori based on known
      melanoma clinical or prognostic characteristics, were analysed for association
      with progression-free survival and overall survival using univariate and
      multivariate analyses and assessed for hierarchical effect on outcomes using
      regression tree analyses. We also analysed factors identified after baseline, on
      treatment, and at progression, for associations with survival after progression.
      The trials included in this analysis are registered with ClinicalTrials.gov:
      BRF113220, number NCT01072175; COMBI-d, number NCT01584648; COMBI-v, number
      NCT01597908. FINDINGS: 617 patients were included in this analysis with a median
      follow-up of 20.0 months (range 0-48.0, IQR 10.1-24.8); 396 patients had
      progression events (ie, disease progression or death) and 290 patients had died.
      Median progression-free survival (11.1 months [95% CI 9.7-12.9]), median overall
      survival (25.6 months [23.1-34.3]), 1-year progression-free survival (48% [44
      52]) and overall survival (74% [71-78]), and 2-year progression-free survival
      (30% [26-34]) and overall survival (53% [49-57]) were consistent with those in
      the individual trials. Patients with normal lactate dehydrogenase (LDH)
      concentration and fewer than three organ sites containing metastases (n=237) had
      the longest 1-year progression-free survival (68% [95% CI 62-74]) and overall
      survival (90% [87-94]) and 2-year progression-free survival (46% [40-54]) and
      overall survival (75% [70-81]), whereas patients with LDH concentration at least
      two times the upper limit of normal (n=70) had the shortest 1-year progression
      free survival (8% [3-19]) and overall survival (40% [29-55]) and 2-year
      progression-free survival (2% [0-13]) and overall survival (7% [3-19]). Of
      patients with disease progression (n=379), survival after progression was longest
      in those with progression in baseline or new non-CNS lesions (n=205; median 10.0
      months [95% CI 7.9-12.0]) and shortest in those with new CNS lesions or
      concurrent progression in baseline and new lesions (n=171; median 4.0 months [3.5
      4.9]). INTERPRETATION: Several patient and clinical characteristics at and after
      baseline are associated with outcomes with dabrafenib plus trametinib, and
      durable benefit is possible with targeted treatment in defined patient subsets.
      FUNDING: Novartis.

PMID- 27864014
TI  - Challenges of data sharing: valuable but costly?

PMID- 27864016
TI  - Generation of antigen-specific cytotoxic T lymphocytes with activated B cells.
AB  - BACKGROUND AIMS: Dendritic cells are well known as the most potent antigen
      presenting cells. Nonetheless, their use in immunotherapy has been limited by the
      time-consuming and laborious steps involved in their generation in vitro.
      Therefore, much attention has been placed on alternative antigen-presenting cells
      that are relatively more convenient to manipulate. METHODS: In this study, the
      efficacy of B cells as antigen-presenting cells, compared with dendritic cells,
      in the induction of cytotoxic T lymphocytes against cytomegalovirus-specific
      antigens was evaluated. B cells were isolated from the peripheral blood
      mononuclear cells of healthy individuals, loaded with alpha-galactosylceramide
      for activation, and nucleofected with cytomegalovirus-antigen coding plasmid DNA.
      Antigen-nucleofected B cells or dendritic cells were cocultured with T cells for
      14 days in vitro. RESULTS: The proliferation of cytotoxic T lymphocytes induced
      by B cells was similar to that of those induced by dendritic cells. Additionally,
      the immunogenicity of both sets of cytotoxic T lymphocytes was similar not only
      in interferon-gamma enzyme-linked immunospot assays but also in cytotoxicity
      assays. DISCUSSION: These observations suggest that alpha-galactosylceramide
      loaded B cells could be used as antigen-presenting cells as an alternative to
      dendritic cells. Using B cells has several benefits, including cost-effectiveness
      and being both less time-consuming and less labor-intensive.

PMID- 27864017
TI  - Value-added products from dairy waste using edible fungi.

PMID- 27864018
TI  - Synthesis and biological evaluation of novel 3-O-tethered triazoles of diosgenin
      as potent antiproliferative agents.
AB  - Diosgenin, a promising anticancer steroidal sapogenin, was isolated from
      Dioscorea deltoidea. Keeping its stereochemistry rich architecture intact, a
      scheme for the synthesis of novel diosgenin analogues was designed using Cu (I)
      catalysed alkyne-azide cycloaddition in order to study their structure-activity
      relationship. Both diosgenin and its analogues exhibited interesting anti
      proliferative effect against four human cancer cell lines viz. HBL-100 (breast),
      A549 (lung), HT-29 (colon) and HCT-116 (colon) using [3-(4,5-dimethylthiazolyl-2)
      2,5-diphenyltetrazoliumbromide] (MTT) assay. Among the synthesized analogues, Dgn
      1 bearing a simple phenyl R moiety attached via triazole to the parent molecule
      was identified as the most potent analogue against A549 cancer cell line having
      IC50 of 5.54MUM, better than the positive control (BEZ-235). Dgn-2 and Dgn-5
      bearing o-nitrophenyl and o-cyanophenyl R moieties respectively, displayed
      impressive anti-proliferative activity against all the tested human cancer cell
      lines with IC50 values ranging from 5.77 to 9.44MUM. The structure-activity
      relationship (SAR) revealed that the analogues with simple phenyl R moiety or
      electron withdrawing ortho substituted R moieties seem to have beneficial impact
      on the anti-proliferative activity.

PMID- 27864019
TI  - Bioconversion of 6-(N-methyl-N-phenyl)aminomethyl androstane steroids by
      Nocardioides simplex.
AB  - The newly synthesized (alpha/beta)-diastereomers of 6-(N-methyl-N
      phenyl)aminomethylandrost-4-ene-3,17-dione (5) and 6-(N-methyl-N
      phenyl)aminomethylandrost-4-en-17beta-ol-3-one (6) were firstly investigated as
      substrates for the whole cells of Nocardioides simplex VKM Ac-2033D in comparison
      with their unsubstituted analogs, - androst-4-ene-3,17-dione (1) and androst-4-en
      17beta-ol-3-one (2). 1(2)-Dehydroderivatives were identified as the major
      bioconversion products from all the substrates tested. When using the mixtures of
      (alpha/beta)-stereoisomers of 5 and 6 as the substrates, only beta-stereoisomers
      of the corresponding 1,4-diene-steroids were formed. Along with 1(2)
      dehydrogenation, N. simplex VKM Ac-2033D promoted oxidation of the hydroxyl group
      at C-17 position of 6: both 6(alpha) and 6(beta) were transformed to the
      corresponding 17-keto derivatives. No steroid core destruction was observed
      during the conversion of the 6-substituted androstanes 5 and 6, while it was
      significant when 1 or 2 was used as the substrate. The results suggested high
      potentials of N. simplex VKM Ac-2033D for the generation of novel 1(2)
      dehydroanalogs.

PMID- 27864020
TI  - Regio- and stereoselective reduction of 17-oxosteroids to 17beta-hydroxysteroids
      by a yeast strain Zygowilliopsis sp. WY7905.
AB  - The reduction of 17-oxosteroids to 17beta-hydroxysteroids is one of the important
      transformations for the preparation of many steroidal drugs and intermediates.
      The strain Zygowilliopsis sp. WY7905 was found to catalyze the reduction of C-17
      carbonyl group of androst-4-ene-3,17-dione (AD) to give testosterone (TS) as the
      sole product by the constitutive 17beta-hydroxysteroid dehydrogenase (17beta
      HSD). The optimal conditions for the reduction were pH 8.0 and 30 degrees C with
      supplementing 10g/l glucose and 1% Tween 80 (w/v). Under the optimized
      transformation conditions, 0.75g/l AD was reduced to a single product TS with
      >90% yield and >99% diastereomeric excess (de) within 24h. This strain also
      reduced other 17-oxosteroids such as estrone, 3beta-hydroxyandrost-5-en-17-one
      and norandrostenedione, to give the corresponding 17beta-hydroxysteroids, while
      the C-3 and C-20 carbonyl groups were intact. The absence of by-products in this
      microbial 17beta-reduction would facilitate the product purification. As such,
      the strain might serve as a useful biocatalyst for this important transformation.

PMID- 27864021
TI  - Trio approach reveals higher risk of PD in carriers of severe vs. mild GBA
      mutations.
AB  - Heterozygote GBA (glucosylceramidase beta) mutations increase the risk of
      Parkinson's disease (PD). Data based on the measured frequencies of GBA mutated
      alleles in the healthy population suggest that severe GBA mutations are
      associated with even higher risk for PD. These data, however, are prone to
      methodological biases resulting from the rarity of severe mutations and from
      ethnic-dependent differences in allele frequencies. To overcome these biases, we
      traced 13 Gaucher disease (GD) patients who were compound heterozygotes for one
      mild (N370S) and one severe GBA mutation and who reported a parent with PD. We
      determined the GBA mutation status of all parents and examined them whenever
      possible. While 50% of the parents carried a mild GBA mutation, we hypothesized
      that PD cases would be more likely to carry a severe mutation. We found that
      10/13 PD parents had a severe mutation and only 3/10 carried a mild mutation
      (binomial test P<0.05). Using an unbiased methodology, we show that carriers of
      severe GBA mutations are at higher risk for PD relative to carriers of the mild
      mutations.

PMID- 27864015
TI  - Prediction of overall survival for patients with metastatic castration-resistant
      prostate cancer: development of a prognostic model through a crowdsourced
      challenge with open clinical trial data.
AB  - BACKGROUND: Improvements to prognostic models in metastatic castration-resistant
      prostate cancer have the potential to augment clinical trial design and guide
      treatment strategies. In partnership with Project Data Sphere, a not-for-profit
      initiative allowing data from cancer clinical trials to be shared broadly with
      researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse
      Engineering Assessments and Methods) challenge to not only identify a better
      prognostic model for prediction of survival in patients with metastatic
      castration-resistant prostate cancer but also engage a community of international
      data scientists to study this disease. METHODS: Data from the comparator arms of
      four phase 3 clinical trials in first-line metastatic castration-resistant
      prostate cancer were obtained from Project Data Sphere, comprising 476 patients
      treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients
      treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598
      patients treated with docetaxel, prednisone or prednisolone, and placebo in the
      VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE
      33 trial. Datasets consisting of more than 150 clinical variables were curated
      centrally, including demographics, laboratory values, medical history, lesion
      sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were
      released publicly to be used as training data to predict the outcome of interest
      namely, overall survival. Clinical data were also released for ENTHUSE 33, but
      data for outcome variables (overall survival and event status) were hidden from
      the challenge participants so that ENTHUSE 33 could be used for independent
      validation. Methods were evaluated using the integrated time-dependent area under
      the curve (iAUC). The reference model, based on eight clinical variables and a
      penalised Cox proportional-hazards model, was used to compare method performance.
      Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266
      patients with metastatic castration-resistant prostate cancer were treated with
      placebo alone. FINDINGS: 50 independent methods were developed to predict overall
      survival and were evaluated through the DREAM challenge. The top performer was
      based on an ensemble of penalised Cox regression models (ePCR), which uniquely
      identified predictive interaction effects with immune biomarkers and markers of
      hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC
      0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes
      factor >20). Both the ePCR model and reference models stratified patients in the
      ENTHUSE 33 trial into high-risk and low-risk groups with significantly different
      overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p<0.0001; reference
      model: 2.56, 1.85-3.53, p<0.0001). The new model was validated further on the
      ENTHUSE M1 cohort with similarly high performance (iAUC 0.768). Meta-analysis
      across all methods confirmed previously identified predictive clinical variables
      and revealed aspartate aminotransferase as an important, albeit previously under
      reported, prognostic biomarker. INTERPRETATION: Novel prognostic factors were
      delineated, and the assessment of 50 methods developed by independent
      international teams establishes a benchmark for development of methods in the
      future. The results of this effort show that data-sharing, when combined with a
      crowdsourced challenge, is a robust and powerful framework to develop new
      prognostic models in advanced prostate cancer. FUNDING: Sanofi US Services,
      Project Data Sphere.

PMID- 27864022
TI  - Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting
      TrxR and activating the EGFR proteasomal degradation pathway.
AB  - Non-small cell lung cancer (NSCLC) is the dominant type of lung cancer. Molecular
      targeting has highly improved the treatment efficacy of lung cancer, but new
      challenges have emerged, such as gefitinib-resistance and cancer recurrence.
      Therefore, new chemotherapeutic agents and treatment strategies are urgently
      needed. Shikonin is the main active component of a Chinese medicinal plant 'Zi
      Cao', which has been shown to exhibit powerful anti-cancer activity in certain
      types of cancer; however, its activity in gefitinib-resistant lung cancer has
      never been addressed. In this study, we used a high-throughput screening assay
      for epidermal growth factor receptor (EGFR) inhibitors and discovered that
      Shikonin is a potent inhibitor of EGFR. The cytotoxicity of Shikonin and its anti
      cancer mechanism in NSCLC was deeply explored. Shikonin exhibited selective
      cytotoxicity among two NSCLC cell lines (H1975 and H1650) and one normal lung
      fibroblast cell line (CCD-19LU). Shikonin significantly increased the activity of
      caspases and poly (ADP-ribosyl) polymerase (PARP), which are indicators of
      apoptosis, and the intensity of ROS by greater than 10-fold. NAC, an inhibitor of
      ROS, completely blocked apoptosis, caspase and PARP activation induced by
      Shikonin. Shikonin remarkably suppressed the phosphorylation of EGFR and led to
      EGFR degradation. The enhancement of ROS generation in H1650 and H1975 gefitinib
      resistant NSCLC cells leads to impairment of growth and induction of apoptosis,
      whereas modulation of EGFR degradation and its downstream signalling pathways by
      Shikonin contributes to its anti-tumour properties in H1975 gefitinib-resistant
      NSCLC cells (with T790M and L858R activating mutations). Shikonin-induced cell
      apoptosis is closely associated with ROS elevation in the cells. These findings
      indicate that Shikonin can be an effective small molecule treating gefitinib
      resistant NSCLC.

PMID- 27864023
TI  - Association of ORAI1 gene polymorphisms with chronic spontaneous urticaria and
      the efficacy of the nonsedating H1 antihistamine desloratadine.

PMID- 27864025
TI  - Heterotaxy syndrome with and without spleen: Different infection risk and
      management.

PMID- 27864024
TI  - Efficacy and safety of the SQ house dust mite sublingual immunotherapy tablet in
      Japanese adults and adolescents with house dust mite-induced allergic rhinitis.
AB  - BACKGROUND: The SQ house dust mite (HDM) sublingual immunotherapy (SLIT) tablet
      has been approved in 11 European countries and Japan for patients with HDM
      induced respiratory allergic disease. OBJECTIVE: This trial was conducted to
      confirm the efficacy and safety of the SQ HDM SLIT tablet in Japanese patients
      with moderate-to-severe HDM-induced allergic rhinitis (AR). METHODS: The trial
      was a randomized, double-blind, placebo-controlled trial including 946 Japanese
      adults and adolescents (12-64 years). Subjects were randomly assigned to daily
      treatment with the SQ HDM SLIT tablet at a dose of 10,000 Japanese allergy units
      (JAU) or 20,000 JAU or to placebo (1:1:1). The primary end point was the total
      combined rhinitis score (TCRS), which is composed of AR symptom and medication
      scores during the efficacy evaluation period. Symptom and medication scores of AR
      and conjunctivitis, rhinitis quality of life, and symptom-free and symptom-severe
      days were evaluated as secondary end points. RESULTS: Analysis of the primary end
      point demonstrated statistically significant reductions in TCRSs of 1.15 (22%, P
      < .001) in the 10,000-JAU group and 0.99 (19%, P < .001) in the 20,000-JAU group
      compared with the placebo group. The statistically significant treatment effect
      was evident from 12 weeks of treatment onward. All secondary end points, except
      AR medication score, were statistically significant in favor of active treatment
      compared with placebo. Post hoc analysis of TCRSs in adolescents showed the same
      efficacy as in adults (P < .05). The treatment was well tolerated by both adults
      and adolescents. CONCLUSION: The trial confirmed the efficacy and safety profile
      of the SQ HDM SLIT tablet in Japanese adult and adolescent patients with moderate
      to-severe HDM-induced AR. These data support the robust efficacy and safety
      profile of previously reported European data.

PMID- 27864026
TI  - B cells differentiate in human thymus and express AIRE.

PMID- 27864027
TI  - Patterns of neural activity predict picture-naming performance of a patient with
      chronic aphasia.
AB  - Naming objects represents a substantial challenge for patients with chronic
      aphasia. This could be in part because the reorganized compensatory language
      networks of persons with aphasia may be less stable than the intact language
      systems of healthy individuals. Here, we hypothesized that the degree of
      stability would be instantiated by spatially differential neural patterns rather
      than either increased or diminished amplitudes of neural activity within a
      putative compensatory language system. We recruited a chronic aphasic patient
      (KL; 66 year-old male) who exhibited a semantic deficit (e.g., often said "milk"
      for "cow" and "pillow" for "blanket"). Over the course of four behavioral
      sessions involving a naming task performed in a mock scanner, we identified
      visual objects that yielded an approximately 50% success rate. We then conducted
      two fMRI sessions in which the patient performed a naming task for multiple
      exemplars of those objects. Multivoxel pattern analysis (MVPA) searchlight
      revealed differential activity patterns associated with correct and incorrect
      trials throughout intact brain regions. The most robust and largest cluster was
      found in the right occipito-temporal cortex encompassing fusiform cortex, lateral
      occipital cortex (LOC), and middle occipital cortex, which may account for the
      patient's propensity for semantic naming errors. None of these areas were found
      by a conventional univariate analysis. By using an alternative approach, we
      extend current evidence for compensatory naming processes that operate through
      spatially differential patterns within the reorganized language system.

PMID- 27864029
TI  - Time-frequency phase-synchrony approaches with ERPs.
AB  - Time-frequency signal processing approaches are well-developed, and have been
      widely employed for the study of the energy distribution of event-related
      potential (ERP) data across time and frequency. Wavelet time-frequency transform
      (TFT) and Cohen's class of time-frequency distributions (TFD) are the most widely
      used in the field. While ERP TFT approaches have been most extensively developed
      for amplitude measures, reflecting the magnitude of regional neuronal activity,
      time-frequency phase-synchrony measures have gained increased utility in recent
      years for the assessment of functional connectivity. Phase synchrony measures can
      be used to index the functional integration between regions (interregional), in
      addition to the consistency of activity within region (intertrial). In this
      paper, we focus on a particular class of time-frequency distributions belonging
      to Cohen's class, known as the Reduced Interference Distribution (RID) for
      quantifying functional connectivity, which we recently introduced (Aviyente et
      al., 2011). The present report first summarizes common time-frequency approaches
      to computing phase-synchrony with ERP data in order to highlight the similarities
      and differences relative to the RID. In previous work, we demonstrated
      differences between the RID and wavelet approaches to indexing phase-synchrony,
      and have applied the RID to demonstrate that RID-based time-frequency phase
      synchrony measures can index increased functional connectivity between medial and
      lateral prefrontal regions during control processing, observed in the theta band
      during the error-related negativity (ERN). Because ERN amplitude measures have
      been associated with two other widely studied medial-frontal theta components (no
      go N2; feedback negativity, FN), the application of the RID phase synchrony
      measure in the present report extends our previous work with ERN to include theta
      activity during the no-go N2 (inhibitory processing) and the feedback negativity
      (FN; loss feedback processing). Findings support the idea that similar medial
      lateral prefrontal functional connectivity underlies the ERN, no-go N2, and FN
      components, and provide initial validation that the proposed RID-based time
      frequency phase-synchrony measure can index this activity.

PMID- 27864028
TI  - Anti-TNF therapy is able to stabilize bowel damage progression in patients with
      Crohn's disease. A study performed using the Lemann Index.
AB  - AIMS: The Lemann Index (LI) was developed to assess the cumulative structural
      damage of the intestinal tract in patients with Crohn's Disease (CD)
      independently of clinical and biochemical activity. Recently, the goal of CD
      focused on obtaining mucosal healing and deep remission rather than simple
      symptom control. These new therapeutic aims emphasize the need to prevent
      progression of bowel damage. In this study we aimed to evaluate the influence of
      different treatments on structural damage progression, assessed by means of LI in
      a series of CD patients consistently treated with various drugs. METHODS: The LI
      was calculated at inclusion and at the end of follow-up in 104 CD patients
      subdivided according to treatments received: biological drugs (n=40, 38.4%),
      azathioprine (n=19, 18.3%), and mesalazine (n=45, 43.3%). RESULTS: The median
      follow-up was 29 months, with no difference among groups. During follow-up, the
      median LI was stable in the biological group [from 6.3 (range, 0.6-37.3) to 6.4
      (range, 0.6-37.6), P=0.543], whereas it significantly increased from 4.1 (range,
      0.6-30) to 8.3 (range, 0.6-31.8) in the azathioprine group (P=0.0006), and from
      2.4 (range, 0.6-25.8) to 4.1 (range, 0.6-28.8) in the mesalazine group
      (P<0.0001). Also during follow-up the LI increased significantly (P=0.004) in the
      azathioprine (68.4%) and mesalazine (60.0%) groups as compared with the
      biological therapy group (30.0%). CONCLUSIONS: In CD patients the LI tends to
      increase over time, although the use of biological drugs rather than azathioprine
      or mesalazine seems to be able to reduce the progressive bowel damage.

PMID- 27864031
TI  - Fractional CO2 Laser Treatment of the Vestibule for Patients with Vestibulodynia
      and Genitourinary Syndrome of Menopause: A Pilot Study.
AB  - INTRODUCTION: Chronic vulvar pain and burning remains one of the most perplexing
      problems faced by practicing gynecologists. AIM: To evaluate the effectiveness
      and safety of the application of micro-ablative fractional CO2 laser to the
      vulvar vestibule in the management of patients with vulvar pain from
      vestibulodynia or genitourinary syndrome of menopause. METHODS: Patients (N = 70)
      underwent fractional micro-ablative CO2 laser treatment for vestibular pain plus
      vestibulodynia (n = 37) or genitourinary syndrome of menopause (n = 33).
      Inclusion criteria were the existence of vestibular atrophic changes and the
      absence of moderate or severe pelvic floor hypertonic dysfunction. MAIN OUTCOME
      MEASURES: A visual analog scale of pain and the Marinoff score of dyspareunia
      were chosen to evaluate improvement. Grading of vestibular health also was
      quantified using a four-point scoring system (0 = no atrophy, 3 = severe
      atrophy). Data were collected at baseline, at weeks 4, 8, and 12, and 4 months
      after the final treatment. RESULTS: For visual analog scale and dyspareunia
      scoring and for the overall vestibular health index scoring, statistically
      significant improvement was noted after three sessions of vestibular fractional
      CO2 laser treatment. Improvement gradually increased throughout the study period
      and was maintained through the 4-month follow-up visit. There was no
      statistically significant difference in outcomes between the two study groups. No
      adverse events from fractional CO2 laser treatment were noted. Overall, 67.6% of
      patients stated significant improvement from the laser procedure. CONCLUSION:
      This preliminary case series showed encouraging results using fractional CO2
      laser treatment of the vestibule in women with vestibulodynia and genitourinary
      syndrome of menopause.

PMID- 27864030
TI  - Incident Heart Failure and Cognitive Decline: The Atherosclerosis Risk in
      Communities Study.
AB  - BACKGROUND: Cognitive impairment is found in a significant proportion of patients
      with heart failure (HF). Although cognitive impairment may be a consequence of
      HF, early signs of cognitive impairment may also indicate subclinical vascular
      disease, and thus a risk factor for future cardiovascular events. METHODS AND
      RESULTS: The Atherosclerosis Risk in Communities Study is a prospective cohort
      study of the development of atherosclerosis. Cox proportional hazards regression
      was used to examine the association between mean 6-year change in cognitive
      function and incident HF in 7962 white and 1933 African-American men and women
      aged 46 to 70 years and free of clinical stroke. Scores were obtained for the
      Delayed Word Recall Test, the Digit Symbol Substitution Test (DSST), and the Word
      Fluency Test. There was a significantly increased risk of developing HF during
      the mean 12.6-year follow-up period after adjustment for age, gender, race, and
      education for those in the quartile with the greatest decline in DSST scores
      (hazard ratio [HR] = 1.17, P = .009), and in the quartile with the lowest
      baseline DSST scores (HR = 1.43, P < .001). CONCLUSIONS: The results suggest that
      relatively low performance on a test of information processing speed may serve as
      an indicator of HF risk in middle age.

PMID- 27864033
TI  - Bronchiectasis: shaking off its orphan status.

PMID- 27864032
TI  - alpha1A-Adrenergic Receptor Antagonism Improves Erectile and Cavernosal Responses
      in Rats With Cavernous Nerve Injury and Enhances Neurogenic Responses in Human
      Corpus Cavernosum From Patients With Erectile Dysfunction Secondary to Radical
      Prostatectomy.
AB  - INTRODUCTION: Cavernous nerve injury (CNI) in rats and radical prostatectomy (RP)
      in men result in loss of nitrergic function and increased adrenergic-neurogenic
      contractions of cavernosal tissue. AIM: To evaluate the modulation of the alpha
      adrenergic system as a strategy to relieve erectile dysfunction (ED) and
      functional cavernosal alterations induced by CNI. METHODS: A non-selective alpha
      blocker (phentolamine 1 mg/kg daily), a selective alpha1A-blocker (silodosin
      [SILOD] 0.1 mg/kg daily), or vehicle was orally administered for 4 weeks after
      bilateral crush CNI (BCNI). Erectile and neurogenic responses of the corpus
      cavernosum (CC) were evaluated. The acute effects of SILOD also were evaluated in
      vivo (0.03 mg/kg intravenously) and ex vivo (10 nmol/L). The effects of SILOD and
      tadalafil (TAD) on nitrergic relaxations were determined in human CC from
      patients with ED with a vascular etiology or ED secondary to RP. MAIN OUTCOME
      MEASURES: Erectile responses in vivo in rats and neurogenic contractions and
      relaxations of rat and human CC. RESULTS: Long-term treatment with SILOD
      significantly improved erectile responses and allowed for the potentiation of
      erectile responses by acute treatment with TAD (0.3 mg/kg intravenously) in rats
      with BCNI. SILOD partly recovered nitrergic relaxations and normalized neurogenic
      contractions in CC from rats with BCNI. Long-term treatment with SILOD partly
      prevented BCNI-induced decreases in neuronal nitric oxide synthase expression.
      Acute administration of SILOD (0.03 mg/kg intravenously) improved erectile
      responses in vivo and potentiated nitrergic relaxation and decreased neurogenic
      contractions ex vivo in CC from rats with BCNI. In human CC from patients with ED
      with a vascular etiology, TAD (30 nmol/L), SILOD (10 nmol/L), or their
      combination increased nitrergic relaxations. Potentiation by TAD was lost in
      human CC from patients with ED after RP but was recovered after co-treatment with
      SILOD. CONCLUSION: alpha-Adrenergic modulation, especially selective alpha1A
      blockade, improves erectile and cavernosal functions after BCNI. Modulation of
      the adrenergic system, mainly in combination strategies, could have a role in the
      management of ED after RP.

PMID- 27864034
TI  - 2016 CHEST annual meeting.

PMID- 27864035
TI  - 47th Union World Conference on Lung Health.

PMID- 27864036
TI  - Comorbidities and the risk of mortality in patients with bronchiectasis: an
      international multicentre cohort study.
AB  - BACKGROUND: Patients with bronchiectasis often have concurrent comorbidities, but
      the nature, prevalence, and impact of these comorbidities on disease severity and
      outcome are poorly understood. We aimed to investigate comorbidities in patients
      with bronchiectasis and establish their prognostic value on disease severity and
      mortality rate. METHODS: An international multicentre cohort analysis of
      outpatients with bronchiectasis from four European centres followed up for 5
      years was done for score derivation. Eligible patients were those with
      bronchiectasis confirmed by high-resolution CT and a compatible clinical history.
      Comorbidity diagnoses were based on standardised definitions and were obtained
      from full review of paper and electronic medical records, prescriptions, and
      investigator definitions. Weibull parametric survival analysis was used to model
      the prediction of the 5 year mortality rate to construct the Bronchiectasis
      Aetiology Comorbidity Index (BACI). We tested the BACI as a predictor of outcomes
      and explored whether the BACI added further prognostic information when used
      alongside the Bronchiectasis Severity Index (BSI). The BACI was validated in two
      independent international cohorts from the UK and Serbia. FINDINGS: Between June
      1, 2006, and Nov 22, 2013, 1340 patients with bronchiectasis were screened and
      986 patients were analysed. Patients had a median of four comorbidities (IQR 2-6;
      range 0-20). 13 comorbidities independently predicting mortality rate were
      integrated into the BACI. The overall hazard ratio for death conferred by a one
      point increase in the BACI was 1.18 (95% CI 1.14-1.23; p<0.0001). The BACI
      predicted 5 year mortality rate, hospital admissions, exacerbations, and health
      related quality of life across all BSI risk strata (p<0.0001 for mortality and
      hospital admissions, p=0.03 for exacerbations, p=0.0008 for quality of life).
      When used in conjunction with the BSI, the combined model was superior to either
      model alone (p=0.01 for combined vs BACI; p=0.008 for combined vs BSI).
      INTERPRETATION: Multimorbidity is frequent in bronchiectasis and can negatively
      affect survival. The BACI complements the BSI in the assessment and prediction of
      mortality and disease outcomes in patients with bronchiectasis. FUNDING: European
      Bronchiectasis Network (EMBARC).

PMID- 27864037
TI  - Early monitoring and quantitative evaluation of macrophage infiltration after
      experimental traumatic brain injury: A magnetic resonance imaging and flow
      cytometric analysis.
AB  - The inflammatory response following traumatic brain injury (TBI) is regulated by
      phagocytic cells. These cells comprising resident microglia and infiltrating
      macrophages play a pivotal role in the interface between early detrimental and
      delayed beneficial effects of inflammation. The aim of the present study was to
      monitor the early effect of monocyte/phagocytic accumulation and further to
      explore its kinetics in TBI mice. Localized macrophage population was monitored
      using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle enhanced in
      vivo serial magnetic resonance imaging (MRI). Flow cytometry based gating study
      was performed to discriminate between resident microglia (Ly6G-CD11b+CD45low) and
      infiltrating macrophages (Ly6G-CD11b+CD45high) at the injury site. The T2*
      relaxation analysis revealed that maximum macrophage infiltration occurs between
      66 and 72h post injury (42-48h post administration of USPIO) at the site of
      inflammation. This imaging data was well supported by iron oxide specific
      Prussian blue staining and macrophage specific F4/80 immunohistochemistry (IHC)
      analysis. Quantitative real-time PCR analysis found significant expression of
      monocyte chemoattractant protein-1 (MCP-1) at 72h post injury. Also, we found
      that flow cytometric analysis demonstrated a 7-fold increase in infiltrating
      macrophages around 72h post injuries as compared to control. The MR imaging in
      combination with flow cytometric analysis enabled the dynamic measurement of
      macrophage infiltration at the injury site. This study may help in setting an
      optimal time window to intervene and prevent damage due to inflammation and to
      increase the therapeutic efficacy.

PMID- 27864038
TI  - A systematic review with meta-analysis of fluticasone furoate/vilanterol
      combination for the treatment of stable COPD.
AB  - BACKGROUND: Current guidelines recommend the use of inhaled corticosteroids/long
      acting beta2-agonists as first-line therapy for COPD patients at risk for acute
      exacerbations and/or severe airflow limitation. This systematic review assesses
      available evidence on the efficacy and safety of fluticasone furoate/vilanterol
      (FF/VI) combination versus each alone, for the treatment of patients with severe
      to very severe stable COPD. METHODS: Randomized, placebo-controlled trials of >8
      weeks of duration were included. Primary end points were pulmonary function, COPD
      exacerbations and serious adverse events. FF/VI was compared with its mono
      components. RESULTS: Five reports with six trials (n = 15,515 patients) met the
      entry criteria. FF/VI was associated with significant increases in trough FEV1
      compared with vilanterol (VI) and fluticasone furoate (FF) (45 mL and 90 mL
      respectively). FF/VI significantly reduced the number of subjects with at least
      one moderate to severe exacerbation compared with VI (number needed to treat for
      benefit [NNTB] = 21) and with FF (NNTB = 26). There were no statistical
      differences in the rates of serious adverse events, cardiac events and all-cause
      mortality. On the contrary, FF/VI showed a significant 52% increase in the rate
      of pneumonia compared with VI monotherapy (5.3% vs. 3.5%). However, there was no
      difference in the rate of pneumonia when FF/VI was compared with FF alone.
      CONCLUSIONS: FF/VI combination was associated with a decrease of the rate of COPD
      exacerbations, without affecting mortality or cardiovascular outcomes in patients
      with moderate to severe stable COPD. Also, the use of FF was associated with an
      increased risk of pneumonia.

PMID- 27864039
TI  - Effects of the sequence and orientation of an expression cassette in tobacco
      transformed by dual Bt genes.
AB  - This study investigated the effects of the sequence arrangement and orientation
      of a target gene expression cassette in vectors on expression levels to determine
      the optimal combination for highly efficient multi-gene expression. Five plant
      transformation vectors were constructed using dual Bt genes, Cry1Ac and Cry3A,
      which differed in the sequence arrangement and orientation of the target gene
      expression cassette. Through an Agrobacterium-mediated method, 5 vectors were
      used for the genetic transformation of tobacco to obtain transgenic lines.
      Fluorescence quantitative PCR showed that the target genes were expressed at the
      transcriptional level, which did not differ significantly among the different
      vectors. However, an enzyme-linked immunosorbent assay showed that there were
      significant differences in the toxin expression levels of the different vectors.
      In vectors N12 and N19, the Cry1Ac gene, located upstream, showed lower average
      expression than the Cry3A gene, located downstream. Similarly, in vectors N13 and
      N18, the Cry3A gene, located upstream, had lower expression than the downstream
      Cry1Ac gene. For vector N21, with the expression cassette containing the Cry1Ac
      gene located upstream in a trans-arrangement and that of the Cry3A gene located
      downstream in a cis-arrangement, the Cry1Ac and Cry3A toxin levels were the
      highest, at 7.41 and 13.24MUg.g-1, respectively. The insect resistance of
      transgenic lines transformed by the different vectors was related to the Bt toxin
      level. Resistance to H. armigera, Lepidoptera, and Cry1Ac toxin level were
      positively correlated; resistance to A. germari larvae, Coleoptera, and Cry3A
      toxin content were also positively correlated. This study showed that the
      sequence arrangement of 2 expression cassettes with target genes may be the key
      to the target gene expression. Two expression cassettes in the same orientation
      had little influence on gene expression; however, when the 2 expression cassettes
      were in the reverse arrangement, the expression of both of the target genes was
      promoted to a certain extent.

PMID- 27864040
TI  - Study of circadian rhythmicity of physiological response and skin temperature of
      sheep during summer and winter in semi-arid tropical environment.
AB  - The present study aimed to evaluate the circadian rhythmicity of some
      physiological variables, including rectal temperature (RT), respiration rate
      (RR), heart rate (HR) and skin temperature (ST) in sheep during the summer and
      winter in semi-arid tropical environment. Eight Malpura rams of 3-4year of age
      with an average body weight of 37.1+/-1.99kg were selected for the study. All the
      animals were fed individually for a maintenance requirement on a body weight
      basis. The RT, RR, HR and ST values were measured in each animal at 3hour
      intervals for 24 consecutive hours. Ambient temperature (DBT) and relative
      humidity (RH) was also recorded inside the shed at the time of physiological
      parameter study. The cosinor analysis showed a daily circadian rhythm (P<0.01) in
      RR, HR and ST values during the summer and winter in sheep under semi-arid
      environment. The RR, HR and ST differ significantly (P<0.05) between summer and
      winter. The amplitude of RR, RT and ST differ significantly (P<0.05) between the
      seasons. The results indicate that the circadian rhythmicity of RR, HR, RT and ST
      during summer and winter changed as expected in compliance to the seasonal
      requirements of animal's adaptability.

PMID- 27864041
TI  - Apnea-hypopnea index prediction through an assessment of autonomic influence on
      heart rate in wakefulness.
AB  - With the high prevalence of obstructive sleep apnea, the issue of developing a
      practical tool for obstructive sleep apnea screening has been raised.
      Conventional obstructive sleep apnea screening tools are limited in their ability
      to help clinicians make rational decisions due to their inability to predict the
      apnea-hypopnea index. Our study aimed to develop a new prediction model that can
      provide a reliable apnea-hypopnea index value during wakefulness. We hypothesized
      that patients with more severe obstructive sleep apnea would exhibit more
      attenuated waking vagal tone, which may result in lower effectiveness in
      decreasing heart rate as a response to deep inspiration breath-holding. Prior to
      conducting nocturnal in-laboratory polysomnography, 30 non-obstructive sleep
      apnea (apnea-hypopnea index<5events/h) subjects and 246 patients with obstructive
      sleep apnea participated in a 75-second experiment that consisted of a 60-second
      baseline measurement and consecutive 15-second deep inspiration breath-hold
      sessions. Two apnea-hypopnea index predictors were devised by considering the
      vagal activities reflected in the electrocardiographic recordings acquired during
      the experiment. Using the predictors obtained from 184 individuals, regression
      analyses and k-fold cross-validation tests were performed to develop an apnea
      hypopnea index prediction model. For the remaining 92 individuals, the developed
      model provided an absolute error (mean+/-SD) of 3.53+/-2.67events/h and a
      Pearson's correlation coefficient of 0.99 (P<0.01) between the apnea-hypopnea
      index predictive values and the reference values reported by polysomnography. Our
      study is the first to achieve reliable and time-efficient prediction of the apnea
      hypopnea index during wakefulness.

PMID- 27864042
TI  - Migratory behavior, metabolism, oxidative stress and mercury concentrations in
      marine and estuarine European glass eels (Anguilla anguilla).
AB  - The relationships between the migratory behavior, methylmercury (MeHg)
      concentrations, oxidative stress response and detoxification processes were
      investigated in glass eels collected in marine (Molliets) and estuarine (Urt)
      waters (Adour estuary, South West France) at the end of the fishing season
      (April). Glass eel migratory behavior was investigated in an experimental flume
      according to their response to dusk. Fish responding to the decrease in light
      intensity by ascending in the water column and moving with or against the flow
      were considered as having a high propensity to migrate (migrant). Glass eels
      still sheltering at the end of the 24h catching period were considered as having
      a low propensity to migrate and were called non-migrant. Our results provide some
      evidence that estuarine glass eels were bigger, presented a higher propensity to
      migrate and a lower oxidative stress response than marine glass eels. This might
      reflect a selection process, some marine glass eels progressively settling or
      dying before reaching Urt and/or a change in feeding behavior. In April, glass
      eels restart feeding in the Adour estuary which might decrease the oxidative
      stress possibly related to starvation, and enhance migration. MeHg concentrations
      was significantly higher in non-migrant than in migrant glass eels and it is
      suggested that non-migrant glass eels might present a higher vulnerability to
      stress (at least contamination and/or starvation), although the underlying
      mechanisms remain to be elucidated.

PMID- 27864043
TI  - Maternal trans fat intake during pregnancy or lactation impairs memory and alters
      BDNF and TrkB levels in the hippocampus of adult offspring exposed to chronic
      mild stress.
AB  - This study aimed to assess the influence of maternal dietary fat intake during
      pregnancy or lactation on memory of adult offspring after chronic mild stress
      (CMS) exposure. Female Wistar rats were supplemented daily with soybean oil/fish
      oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0g/kg body
      weight) during pregnancy or lactation. On post-natal day (PND) 60, half of the
      animals were exposed to CMS following behavioral assessments. While the adult
      offspring born under influence of SO/FO and HVF supplementations during pregnancy
      showed higher levels of n-3 and n-6 fatty acids (FA) series DHA and ARA
      metabolites, respectively, in the hippocampus, adult offspring born from
      supplemented dams during lactation showed higher levels of their precursors: ALA
      and LA. However, only HVF supplementation allowed TFA incorporation of adult
      offspring, and levels were higher in lactation period. Adult offspring born from
      dams supplemented with trans fat in both pregnancy and lactation showed short and
      long-term memory impairments before and after CMS. Furthermore, our study also
      showed higher memory impairment in offspring born from HVF-supplemented dams
      during lactation in comparison to pregnancy. BDNF expression was increased by
      stress exposure in offspring from both SO/FO- and HVF-supplemented dams during
      pregnancy. In addition, offspring from HVF-supplemented dams showed decreased
      TrkB expression in both supplemented periods, regardless of stress exposure. In
      conclusion, these findings show for the first time that the type of dietary FA as
      well as the period of brain development is able to change FA incorporation in
      brain neural membranes.

PMID- 27864044
TI  - Localization Methods for Excisional Biopsy in Women With Nonpalpable Mammographic
      Abnormalities.
AB  - INTRODUCTION: With the advent and proliferation of breast cancer screening
      programs, more women are being diagnosed with mammographic abnormalities that
      require tissue diagnosis. If imaged-guided biopsy is not possible or previous
      image-guided biopsies reveal pathologies that require more extensive surgery,
      guided excisional biopsy/lumpectomy may be necessary. METHODS: Fifteen women were
      enrolled in the study of the feasibility of off-site or day-before wire
      localization excisional biopsy of the breast with mammographic abnormalities.
      Five patients had their localization wire placed the day before, whereas 10
      patients had their localization the same day with surgery in a distant procedure
      room under straight local anesthesia. RESULTS: Two of the 15 patients had an
      eventual cancer diagnosis from their wire-localized excisional breast biopsy. All
      patients had their mammographic abnormality removed with the previously placed
      core biopsy clip, and there was 100% radiologic/clinical correlation. All
      patients' wounds healed primarily without any surgical site infections.
      CONCLUSION: The protocol answers 2 questions concerning the wire-localized
      excisional breast biopsy technique. The series shows that the wire-localization
      technique can be performed the night before or in a location away from the
      procedure room that would allow better synchronization with surgical schedules or
      allow the procedure to take place in low-cost settings away from the expense of
      the hospital operating room.

PMID- 27864045
TI  - Influence of chronic L-DOPA treatment on immune response following allogeneic and
      xenogeneic graft in a rat model of Parkinson's disease.
AB  - Although intrastriatal transplantation of fetal cells for the treatment of
      Parkinson's disease had shown encouraging results in initial open-label clinical
      trials, subsequent double-blind studies reported more debatable outcomes. These
      studies highlighted the need for greater preclinical analysis of the parameters
      that may influence the success of cell therapy. While much of this has focused on
      the cells and location of the transplants, few have attempted to replicate
      potentially critical patient centered factors. Of particular relevance is that
      patients will be under continued L-DOPA treatment prior to and following
      transplantation, and that typically the grafts will not be immunologically
      compatible with the host. The aim of this study was therefore to determine the
      effect of chronic L-DOPA administered during different phases of the
      transplantation process on the survival and function of grafts with differing
      degrees of immunological compatibility. To that end, unilaterally 6-OHDA lesioned
      rats received sham surgery, allogeneic or xenogeneic transplants, while being
      treated with L-DOPA before and/or after transplantation. Irrespective of the L
      DOPA treatment, dopaminergic grafts improved function and reduced the onset of L
      DOPA induced dyskinesia. Importantly, although L-DOPA administered post
      transplantation was found to have no detrimental effect on graft survival, it did
      significantly promote the immune response around xenogeneic transplants, despite
      the administration of immunosuppressive treatment (cyclosporine). This study is
      the first to systematically examine the effect of L-DOPA on graft tolerance,
      which is dependent on the donor-host compatibility. These findings emphasize the
      importance of using animal models that adequately represent the patient paradigm.

PMID- 27864046
TI  - Acute colitis chronically alters immune infiltration mechanisms and sensory neuro
      immune interactions.
AB  - OBJECTIVE: Little is understood regarding how disease progression alters immune
      and sensory nerve function in colitis. We investigated how acute colitis
      chronically alters immune recruitment and the impact this has on re-activated
      colitis. To understand the impact of disease progress on sensory systems we
      investigated the mechanisms underlying altered colonic neuro-immune interactions
      after acute colitis. DESIGN: Inflammation was compared in mouse models of health,
      acute tri-nitrobenzene sulphonic acid (TNBS) colitis, Remission and Reactivated
      colitis. Cytokine concentrations were compared by ELISA in-situ and in explanted
      colon tissue. Colonic infiltration by CD11b/F4-80 macrophage, CD4 THELPER (TH)
      and CD8 TCYTOTOXIC (TC) and alpha4beta7 expression on mesenteric lymph node (MLN)
      TH and TC was determined by flow cytometry. Cytokine and effector receptor mRNA
      expression was determined on colo-rectal afferent neurons and the mechanisms
      underlying cytokinergic effects on high-threshold colo-rectal afferent function
      were investigated using electrophysiology. RESULTS: Colonic damage, MPO activity,
      macrophage infiltration, IL-1beta and IL-6 concentrations were lower in
      Reactivated compared to Acute colitis. TH infiltration and alpha4beta7 expression
      on TH MLN was increased in Remission but not Acute colitis. IFN-gamma
      concentrations, TH infiltration and alpha4beta7 expression on TH and TC MLN
      increased in Reactivated compared to Acute colitis. Reactivated explants secreted
      more IL-1beta and IL-6 than Acute explants. IL-6 and TNF-alpha inhibited colo
      rectal afferent mechanosensitivity in Remission mice via a BKCa dependent
      mechanism. CONCLUSIONS: Acute colitis persistently alters immune responses and
      afferent nerve signalling pathways to successive episodes of colitis. These
      findings highlight the complexity of viscero-sensory neuro-immune interactions in
      painful remitting and relapsing diseases.

PMID- 27864048
TI  - Aversive properties of negative incentive shifts in Fischer 344 and Lewis rats.
AB  - Research on incentive contrast highlights that reward value is not absolute but
      rather is based upon comparisons we make to rewards we have received and expect
      to receive. Both human and nonhuman studies on incentive contrast show that
      shifting from a larger more-valued reward to a smaller less-valued reward is
      associated with long periods of nonresponding - a negative contrast effect. In
      this investigation, we used two different genetic rat strains, Fischer 344 and
      Lewis rats that putatively differ in their sensitivity to aversive stimulation,
      to assess the aversive properties of large-to-small reward shifts (negative
      incentive shifts). Additionally, we examined the extent to which increasing cost
      (fixed-ratio requirements) modulates negative contrast effects. In the presence
      of a cue that signaled the upcoming reward magnitude, lever pressing was
      reinforced with one of two different magnitudes of food (large or small). This
      design created two contrast shifts (small-to-large, large-to-small) and two
      shifts used as control conditions (small-to-small, large-to-large). Results
      showed a significant interaction between rat strain and cost requirements only
      during the negative incentive shift with the emotionally reactive Fischer 344
      rats exhibiting significantly longer response latencies with increasing cost,
      highlighting greater negative contrast. These findings are more consistent with
      emotionality accounts of negative contrast and results of neurophysiological
      research that suggests shifting from a large to a small reward is aversive.
      Findings also highlight how subjective reward value and motivation is a product
      of gene-environment interactions.

PMID- 27864047
TI  - APOEepsilon4 impacts up-regulation of brain-derived neurotrophic factor after a
      six-month stretch and aerobic exercise intervention in mild cognitively impaired
      elderly African Americans: A pilot study.
AB  - Possession of the Apolipoprotein E (APOE) gene epsilon4 allele is the most
      prevalent genetic risk factor for late onset Alzheimer's disease (AD). Recent
      evidence suggests that APOE genotype differentially affects the expression of
      brain-derived neurotrophic factor (BDNF). Notably, aerobic exercise-induced
      upregulation of BDNF is well documented; and exercise has been shown to improve
      cognitive function. As BDNF is known for its role in neuroplasticity and
      survival, its upregulation is a proposed mechanism for the neuroprotective
      effects of physical exercise. In this pilot study designed to analyze exercise
      induced BDNF upregulation in an understudied population, we examined the effects
      of APOEepsilon4 (epsilon4) carrier status on changes in BDNF expression after a
      standardized exercise program. African Americans, age 55years and older,
      diagnosed with mild cognitive impairment participated in a six-month, supervised
      program of either stretch (control treatment) or aerobic (experimental treatment)
      exercise. An exercise-induced increase in VO2Max was detected only in male
      participants. BDNF levels in serum were measured using ELISA. Age, screening MMSE
      scores and baseline measures of BMI, VO2Max, and BDNF did not differ between
      epsilon4 carriers and non-epsilon4 carriers. A significant association between
      epsilon4 status and serum BDNF levels was detected. Non-epsilon4 carriers showed
      a significant increase in BDNF levels at the 6month time point while epsilon4
      carriers did not. We believe we have identified a relationship between the
      epsilon4 allele and BDNF response to physiologic adaptation which likely impacts
      the extent of neuroprotective benefit gained from engagement in physical
      exercise. Replication of our results with inclusion of diverse racial cohorts,
      and a no-exercise control group will be necessary to determine the scope of this
      association in the general population.

PMID- 27864049
TI  - Phosphodiesterase-7 inhibition affects accumbal and hypothalamic thyrotropin
      releasing hormone expression, feeding and anxiety behavior of rats.
AB  - Thyrotropin-releasing hormone (TRH) has anorexigenic and anxiolytic functions
      when injected intraventricularly. Nucleus accumbens (NAcc) is a possible brain
      region involved, since it expresses proTRH. TRH from hypothalamic paraventricular
      nucleus (PVN) has a food intake-regulating role. TRHergic pathways of NAcc and
      PVN are implicated in anxiety and feeding. Both behaviors depend on cAMP and
      phosphorylated-cAMP response element binding protein (pCREB) intracellular
      levels. Intracellular levels of cAMP are controlled by the degrading activity of
      phosphodiesterases (PDEs). Since TRH transcription is activated by pCREB, a
      specific inhibitor of PDE7B may regulate TRH-induced effects on anxiety and
      feeding. We evaluated the effectiveness of an intra-accumbal and intraperitoneal
      (i.p.) administration of a PDE7 inhibitor (BRL-50481) on rats' anxiety-like
      behavior and food intake; also on TRH mRNA and protein expression in NAcc and PVN
      to define its mediating role on the PDE7 inhibitor-induced behavioral changes.
      Accumbal injection of 4MUg/0.3MUL of PDE7 inhibitor decreased rats' anxiety. The
      i.p. injection of 0.2mg/kg of the inhibitor was able to increase the PVN TRH mRNA
      expression and to decrease feeding but did not change animals' anxiety levels; in
      contrast, 2mg/kg b.w inhibitor enhanced accumbal TRH mRNA, induced anxiolysis
      with no change in food intake. PDE7 inhibitor induced anxiolytic and anorexigenic
      like behavior depending on the dose used. Results supported hypothalamic TRH
      mediated feeding-reduction effects, and accumbal TRH mediation of inhibitor
      induced anxiolysis. Thus, an i.p dose of this inhibitor might be reducing anxiety
      with no change in feeding, which could be useful for obese patients.

PMID- 27864050
TI  - Ancestry trumps experience: Transgenerational but not early life stress affects
      the adult physiological stress response.
AB  - Exposure to stressors can affect an organism's physiology and behavior as well as
      that of its descendants (e.g. through maternal effects, epigenetics, and/or
      selection). We examined the relative influence of early life vs.
      transgenerational stress exposure on adult stress physiology in a species that
      has populations with and without ancestral exposure to an invasive predator. We
      raised offspring of eastern fence lizards (Sceloporus undulatus) from sites
      historically invaded (high stress) or uninvaded (low stress) by predatory fire
      ants (Solenopsis invicta) and determined how this different transgenerational
      exposure to stress interacted with the effects of early life stress exposure to
      influence the physiological stress response in adulthood. Offspring from these
      high- and low-stress populations were exposed weekly to either sub-lethal attack
      by fire ants (an ecologically relevant stressor), topical treatment with a
      physiologically-appropriate dose of the stress-relevant hormone, corticosterone
      (CORT), or a control treatment from 2 to 43weeks of age. Several months after
      treatments ended, we quantified plasma CORT concentrations at baseline and
      following restraint, exposure to fire ants, and adrenocorticotropic hormone
      (ACTH) injection. Exposure to fire ants or CORT during early life did not affect
      lizard stress physiology in adulthood. However, offspring of lizards from
      populations that had experienced multiple generations of fire ant-invasion
      exhibited more robust adult CORT responses to restraint and ACTH-injection
      compared to offspring from uninvaded populations. Together, these results
      indicate that transgenerational stress history may be at least as important, if
      not more important, than early life stress in affecting adult physiological
      stress responses.

PMID- 27864052
TI  - Tumor tissue slice cultures as a platform for analyzing tissue-penetration and
      biological activities of nanoparticles.
AB  - The success of therapeutic nanoparticles depends, among others, on their ability
      to penetrate a tissue for actually reaching the target cells, and their efficient
      cellular uptake in the context of intact tissue and stroma. Various nanoparticle
      modifications have been implemented for altering physicochemical and biological
      properties. Their analysis, however, so far mainly relies on cell culture
      experiments which only poorly reflect the in vivo situation, or is based on in
      vivo experiments that are often complicated by whole-body pharmacokinetics and
      are rather tedious especially when analyzing larger nanoparticle sets. For the
      more precise analysis of nanoparticle properties at their desired site of action,
      efficient ex vivo systems closely mimicking in vivo tissue properties are needed.
      In this paper, we describe the setup of organotypic tumor tissue slice cultures
      for the analysis of tissue-penetrating properties and biological activities of
      nanoparticles. As a model system, we employ 350MUm thick slice cultures from
      different tumor xenograft tissues, and analyze modified or non-modified
      polyethylenimine (PEI) complexes as well as their lipopolyplex derivatives for
      siRNA delivery. The described conditions for tissue slice preparation and culture
      ensure excellent tissue preservation for at least 14days, thus allowing for
      prolonged experimentation and analysis. When using fluorescently labeled siRNA
      for complex visualization, fluorescence microscopy of cryo-sectioned tissue
      slices reveals different degrees of nanoparticle tissue penetration, dependent on
      their surface charge. More importantly, the determination of siRNA-mediated
      knockdown efficacies of an endogenous target gene, the oncogenic survival factor
      Survivin, reveals the possibility to accurately assess biological nanoparticle
      activities in situ, i.e. in living cells in their original environment. Taken
      together, we establish tumor (xenograft) tissue slices for the accurate and
      facile ex vivo assessment of important biological nanoparticle properties. Beyond
      the quantitative analysis of nanoparticle tissue-penetration, the excellent
      tissue preservation and cell viability also allows for the evaluation of
      biological activities.

PMID- 27864053
TI  - Studies for improved understanding of lipid distributions in human skin by
      combining stimulated and spontaneous Raman microscopy.
AB  - Advanced Raman techniques, such as stimulated Raman spectroscopy (SRS), have
      become a valuable tool for investigations of distributions of substances in
      biological samples. However, these techniques lack spectral information and are
      therefore highly affected by cross-sensitivities, which are due to blended Raman
      bands. One typical example is the symmetric CH2 stretching vibration of lipids,
      which is blended with the more intense Raman band of proteins. We report in this
      work an approach to reduce such cross-sensitivities by a factor of 8 in human
      skin samples. This is accomplished by careful spectral deconvolutions revealing
      the neat spectra of skin lipids. Extensive Raman studies combining the
      complementary advantages of fast mapping and scanning, i.e. SRS, as well as
      spectral information provided by spontaneous Raman spectroscopy, were performed
      on the same skin regions. In addition, an approach for correcting artifacts is
      reported, which are due to transmission and reflection geometries in Raman
      microscopy as well as scattering of radiation from rough and highly structured
      skin samples. As a result, these developments offer improved results obtained
      from label-free spectromicroscopy provided by Raman techniques. These yield
      substance specific information from spectral regimes in which blended bands
      dominate. This improvement is illustrated by studies on the asymmetric CH2
      stretching vibration of lipids, which was previously difficult to identify due to
      the strong background signal from proteins. The advantage of the correction
      procedures is demonstrated by higher spatial resolution permitting to perform
      more detailed investigations on lipids and their composition in skin.

PMID- 27864051
TI  - Individual differences in speech-in-noise perception parallel neural speech
      processing and attention in preschoolers.
AB  - From bustling classrooms to unruly lunchrooms, school settings are noisy. To
      learn effectively in the unwelcome company of numerous distractions, children
      must clearly perceive speech in noise. In older children and adults, speech-in
      noise perception is supported by sensory and cognitive processes, but the
      correlates underlying this critical listening skill in young children (3-5 year
      olds) remain undetermined. Employing a longitudinal design (two evaluations
      separated by ~12 months), we followed a cohort of 59 preschoolers, ages 3.0-4.9,
      assessing word-in-noise perception, cognitive abilities (intelligence, short-term
      memory, attention), and neural responses to speech. Results reveal changes in
      word-in-noise perception parallel changes in processing of the fundamental
      frequency (F0), an acoustic cue known for playing a role central to speaker
      identification and auditory scene analysis. Four unique developmental
      trajectories (speech-in-noise perception groups) confirm this relationship, in
      that improvements and declines in word-in-noise perception couple with
      enhancements and diminishments of F0 encoding, respectively. Improvements in word
      in-noise perception also pair with gains in attention. Word-in-noise perception
      does not relate to strength of neural harmonic representation or short-term
      memory. These findings reinforce previously-reported roles of F0 and attention in
      hearing speech in noise in older children and adults, and extend this
      relationship to preschool children.

PMID- 27864054
TI  - Ultrasound-assisted extraction of beta-d-glucan from hull-less barley: Assessment
      of physicochemical and functional properties.
AB  - The present study was carried out to investigate the effect of ultrasound
      assisted extraction (UAE) method on physicochemical and molecular properties of
      hull-less barley beta-d-glucan. With increasing sonication time, beta-d-glucan
      flow behavior index (n) and its extraction yield significantly increased while
      its consistency coefficient and lightness decreased. Sonication time had no
      significant effect on beta-d-glucan purity, emulsion and foam stabilizing effect
      and colour. Increasing pH from 5 to 9 significantly enhanced extraction yield,
      purity, consistency coefficient (k), emulsion stabilizing effect and yellowness
      of the final product. At higher pHs, flow behavior index (n) and redness and
      yellowness decreased. With increasing the amplitude, extracted beta-d-glucan flow
      behavior index (n), redness significantly increased. In contrast, beta-d-glucan
      purity, emulsion stability, consistency coefficient (k) and yellowness decreased
      as a result of increase in sound amplitude. However, sound amplitude had no
      significant effect on beta-d-glucan lightness. Models presented in this study
      were highly significant and the correlation coefficient could be used for
      optimization of beta-d-glucan extraction from hull-less barley. Considering the
      importance and desirability of the response variables, the best results were
      obtained when the sonication time, amplitude and pH were 4.8min, 50% and 9,
      respectively. beta-d-Glucans extracted by UAE had lower average molecular weight
      compared to those extracted by water extraction method. There was no difference
      between the chemical structures of beta-d-glucans extracted by UAE and
      conventional method. This means that short time ultrasonic extraction had no
      effect on chemical structure of beta-d-glucan. These results indicate that UAE
      method was a very effective tool for extraction of beta-d-glucan as a potential
      hydrocolloid agent for food industries.

PMID- 27864055
TI  - Gastroprotective effect and chemical characterization of a polysaccharide
      fraction from leaves of Croton cajucara.
AB  - Croton cajucara Benth. is a tree from the Amazon Forest, where it is known as
      sacaca. Its leaves and barks are used in medicinal preparations to treat
      different diseases, including gastric ulcers. The crude polysaccharide fraction
      (CCP), obtained from the hot aqueous extract of C. cajucara leaves, was able to
      promote gastroprotection on an ethanol induced gastric ulcer model. Therefore, a
      bioguided fractionation was performed to isolate the active polysaccharide
      fraction. After freezing-thawing, ultrafiltration and dialyses at 100, 50, and
      25kDa cut-off membranes, fraction 25R was obtained. It contained glucose,
      galactose, rhamnose, arabinose, galacturonic acid and mannose in a 7:5:5:3:1:1
      molar ratio approximately, and had a Mw of 42,840g/mol. Methylation analysis and
      NMR spectroscopy indicated that 25R is a very complex polysaccharide fraction
      containing type I rhamnogalacturonan, arabinan, type I arabinogalactan, type II
      arabinogalactan, rhamnan, starch and mannan. It was able to reduce ethanol
      induced gastric ulcers in rats, through preservation of mucus and GSH levels.

PMID- 27864056
TI  - Lactoferrin nanoparticle mediated targeted delivery of 5-fluorouracil for
      enhanced therapeutic efficacy.
AB  - Malignant melanoma is an aggressive form of skin cancer with high mortality
      rates. Common treatments for malignant melanoma involve a combination of
      radiotherapy and chemotherapy with fluorouracil (5-FU). A major challenge with
      melanoma treatment is active resistance to chemotherapeutic drugs. Superior
      treatment outcome lies on balance involving optimum therapeutic doses and the
      side effects associated with dose escalation. The study aimed to efficiently
      entrap 5-FU in lactoferrin nanoparticles (LfNPs) in an attempt to enhance its
      therapeutic efficacy. 5-FU loaded lactoferrin nanoparticles (5-FU-LfNPs) were
      prepared by sol-oil method with a narrow size distribution of 150+/-20nm 5-FU
      LfNPs exhibits high encapsulation efficiency (64+/-2.3%) and increased storage
      stability at 4 degrees C. Competitive ligand binding and lysosomal colocalization
      studies suggested a receptor mediated uptake for LfNPs internalization in B16F10
      cells. Moreover, 5-FU-LfNPs show a pH dependent drug release similar to endosomal
      pH (pH 5 and 6). In addition compared to free 5-FU, 5-FU- LfNPs showed a higher
      intracellular uptake, prolonged retention and improved cytotoxicity (2.7-fold) in
      melanoma cells (B16F10). To conclude, LfNPs represent a superior nano-carrier for
      the targeted delivery of 5-FU in melanoma cells intended for the efficient
      treatment of melanoma though detailed in vivo investigations are warranted.

PMID- 27864057
TI  - Inhibitory effects of the dietary flavonoid quercetin on the enzyme activity of
      zinc(II)-dependent yeast alcohol dehydrogenase: Spectroscopic and molecular
      docking studies.
AB  - A multispectroscopic exploration was employed to investigate the interaction
      between the metallo-enzyme alcohol dehydrogenase (ADH) from yeast with
      bioflavonoid quercetin (QTN). Here, we have characterized the complex formation
      between QTN and Zn2+ in aqueous solution and then examined the effect of such
      complex formation on the enzymatic activity of a zinc(II)-dependent enzyme
      alcohol dehydrogenase from yeast. We have observed an inhibition of enzymatic
      activity of ADH in presence of QTN. Enzyme inhibition kinetic experiments
      revealed QTN as a non-competitive inhibitor of yeast ADH. Perturbation of
      Circular dichroic (CD) spectrum of ADH in presence of QTN is observed due to the
      structural changes of ADH on complexation with the above flavonoid. Our results
      indicate a conformational change of ADH due to removal of Zn2+ present in the
      enzyme by QTN. This was further established by molecular modeling study which
      shows that the flavonoid binds to the Zn2+ ion which maintains the tertiary
      structure of the metallo-enzyme. So, QTN abstracts only half of the Zn2+ ions
      present in the enzyme i.e. one Zn2+ ion per monomer. From the present study, the
      structural alteration and loss of enzymatic activity of ADH are attributed to the
      complex formation between QTN and Zn2+.

PMID- 27864058
TI  - A novel alkaline surfactant-stable keratinase with superior feather-degrading
      potential based on library screening strategy.
AB  - A novel keratinase was mined and expressed in Escherichia coli BL21 (DE3) via
      function-driven screening with fosmid library. The catalytic properties of
      purified keratinase were investigated in detail following enzyme purification.
      The recombinant keratinase was purified to homogeneity with an estimated
      molecular weight of 26kDa using nickel affinity chromatography, of which the
      optimal reaction pH and temperature were 10.0 and 55 degrees C, respectively. It
      could remain stable at pH 5.0-12.0 and 40-60 degrees C. Metal ions such as Ca2+,
      Mn2+, Ag+, Na+, Mg2+, Li+, Sn2+ (1mM) displayed positive influence on keratinase,
      and particularly, Ca2+ exhibited remarkable improvement effect by 2.6 folds. It
      was strongly inhibited by PMSF as a protease inhibitor. On the contrary, it could
      be obviously activated by various surfactants, such as Tween 40 and Triton X-114.
      The recombinant keratinase showed high specificity towards casein, soluble
      keratin, BSA, and wool. The keratinase could efficiently degrade the feathers,
      which demonstrated its applicable potential for biodegradation of keratin wastes
      and regeneration of soluble protein.

PMID- 27864059
TI  - Biosynthesis and physicochemical characterization of a bacterial
      polysaccharide/polyamide blend, applied for microfluidics study in porous media.
AB  - Screening among some new isolated bacteria from oily samples, which were capable
      of producing extracellular polymeric substances (EPSs), one was selected and
      identified as Bacillus sonorensis. An efficient micro-total analysis approach was
      carried out to assay the produced EPSs by this bacterium. Sucrose and yeast
      concentrations as carbon and nitrogen sources, respectively, sodium salt
      concentration and initial pH were selected to be the variables in experimental
      design. Production of EPS in optimal condition was increased by 5.3 times.
      Further EPS purification was carried out to identify the biopolymers. The
      bacteria produced high molecular weight biopolymers with a number average
      molecular weight (Mn) of 9.1*106g/mol determined by gel permeation chromatography
      (GPC). Biopolymer characterization demonstrated the biosynthesis of both
      polysaccharides and polyamides by the bacteria. For the biopolymer blend, thermal
      properties and morphological characteristics were studied using simultaneous
      differential scanning calorimetric and thermal gravimetric analyses (DSC/TGA) and
      field emission scanning electron microscope (FESEM) analyses. Finally, the
      biopolymer blend was injected into an oil saturated glass micro model to study
      the enhancement of oil recovery by biopolymer flooding in contrast with water
      flooding. It was found that oil recovery increased by 36%, from 23% using water
      flooding to 59% for biopolymer injection.

PMID- 27864060
TI  - FOS-1 functions as a transcriptional activator downstream of the C. elegans JNK
      homolog KGB-1.
AB  - JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK
      homolog KGB-1 plays essential roles in protection from heavy metals and protein
      folding stress. However, the contributions of KGB-1 are age-dependent, providing
      protection in larvae, but reducing stress resistance and shortening lifespan in
      adults. Attenuation of DAF-16 was linked to the detrimental contributions of KGB
      1 in adults, but its involvement in KGB-1-dependent protection in larvae remains
      unclear. To characterize age-dependent contributions of KGB-1, we used microarray
      analysis to measure gene expression following KGB-1 activation either in
      developing larvae or in adults, achieved by knocking down its negative
      phosphatase regulator vhp-1. This revealed a robust KGB-1 regulon, most of which
      consisting of genes induced following KGB-1 activation regardless of age; a
      smaller number of genes was regulated in an age-dependent manner. We found that
      the bZIP transcription factor FOS-1 was essential for age-invariant KGB-1
      dependent gene induction, but not for age-dependent expression. The latter was
      more affected by DAF-16, which was further found to be required for KGB-1
      dependent cadmium resistance in larvae. Our results identify FOS-1 as a
      transcriptional activator mediating age-invariant contributions of KGB-1,
      including a regulatory loop of KGB-1 signaling, but also stress the importance of
      DAF-16 as a mediator of age-dependent contributions.

PMID- 27864062
TI  - En Face Optical Coherence Tomography Imaging for the Detection of Nascent
      Geographic Atrophy.
AB  - PURPOSE: To determine if en face optical coherence tomography (OCT) imaging can
      identify nascent geographic atrophy (nGA) in eyes with intermediate age-related
      macular degeneration (iAMD). DESIGN: Retrospective observational case series.
      METHODS: Patients with iAMD from the COMPLETE study at the Bascom Palmer Eye
      Institute were evaluated to determine if nGA was present at baseline and at
      follow-up using high-density Spectralis OCT B-scans and en face OCT images from
      the Cirrus OCT instrument. If available, additional en face OCT images and B
      scans were analyzed at follow-up times beyond the 52-week period. RESULTS: A
      total of 37 eyes (27 patients) were evaluated for at least 1 year using both B
      scans and en face images. Two drusen suspicious for nGA at baseline were
      identified, but neither druse developed GA after 24 and 62 months of follow-up,
      respectively. Another druse displayed hypertransmission into the choroid at week
      52 on B-scan imaging and was classified as nGA. En face OCT imaging identified
      this druse as a focal bright area. Drusen breakdown occurred during a follow-up
      of 39 months. CONCLUSIONS: En face OCT imaging appeared to be as useful as
      routine B-scan imaging for identifying areas suspicious for nGA in this
      population from the COMPLETE Study. Additional longitudinal follow-up of eyes
      with drusen is needed to determine if en face OCT imaging can replace the
      evaluation of individual B-scans for the detection of nGA.

PMID- 27864061
TI  - Melanogenesis inhibits respiration in B16-F10 melanoma cells whereas enhances
      mitochondrial cell content.
AB  - Melanoma is a rare and aggressive skin tumor; the survival of patients diagnosed
      late is fairly low. This high mortality rate is due to the characteristics of the
      cells that allow them to be resistant to radiotherapy and conventional
      chemotherapy, besides of being able to evade the immune system. Melanin, the
      pigment responsible for skin, hair and eye color, seems to be involved in this
      resistance. The main function of melanin is to protect the cells against
      ultraviolet (UV) light by absorbing this radiation and reactive oxygen species
      (ROS) scavenging. But this pigment may have also a role as photosensitizer,
      because when it is irradiated with UVA light (320-400 nm), the generation of ROS
      was detected. Besides, the melanogenesis stimulation on B16-F10 cells resulted in
      cell cycle arrest, induction of a quiescent state, change in the expression of
      several proteins and alterations on ADP/ATP ratio. The present study aimed to
      investigate the influence of melanogenesis stimulation in mitochondrial function
      of B16-F10 melanoma cells. Therefore, we analyzed cells respiration,
      mitochondrial membrane potential (Deltapsim) and mitochondria mass in B16-F10
      melanoma cells stimulated with 0.4mML-tyrosine and 10mM NH4Cl. Our results showed
      that the induction of melanin synthesis was able to reduce significantly the
      oxygen consumption after 48h of stimulation, without changes of mitochondrial
      membrane potential when compared to non-stimulated cells. Despite of respiration
      inhibition, the mitochondria mass was higher in cells with melanogenesis
      stimulation. We suggest that the stimulation in the melanin synthesis might be
      promoting the inhibition of electrons transport chain by some intermediate
      compound from the synthesis of the pigment and this effect could contribute to
      explain the entry in the quiescent state.

PMID- 27864063
TI  - Quercetin impregnated chitosan-fibrin composite scaffolds as potential wound
      dressing materials - Fabrication, characterization and in vivo analysis.
AB  - The present study efforts at fabricating chitosan-fibrin composite (CF) scaffolds
      impregnated with quercetin for wound dressing application and aims at
      investigating their physicochemical properties. CF scaffolds were prepared by
      mixing acidic solution of chitosan with an alkaline solution of fibrin, to which
      quercetin (Q) was added, homogenized and lyophilized obtain Q-CF scaffold. FTIR
      spectra were used to determine the interactions between the functional groups of
      quercetin and CF scaffolds. TGA analysis revealed the decomposition of saccharide
      rings and amino acids of chitosan and fibrin at the temperature range of 255-400
      degrees C. Q-CF scaffold exhibited maximum tensile strength of 1.45MPa, an ideal
      mechanical strength for a wound dressing material. Q-CF scaffolds exhibited good
      bactericidal activity against Escherichia coli and Staphylococcus aureus.
      Biocompatibility of Q-CF scaffold was assessed using MTT assay, which elucidated
      its non-toxic property and excellent suitability for tissue engineering
      applications. In vivo wound healing experiments performed using albino rats
      revealed that topical application of Q-CF scaffold on open excision type of
      wounds can significantly accelerate the process of wound healing. These results
      suggest that Q-CF scaffold could serve as a promising wound dressing material.

PMID- 27864064
TI  - An emerging class of amphiphilic dendrimers for pharmaceutical and biomedical
      applications: Janus amphiphilic dendrimers.
AB  - In recent years, a new class of dendrimer, known as Janus dendrimers (JDs), has
      attracted much attention due to their different structures and properties to the
      conventional symmetric forms. The broken symmetry of JDs offers the opportunity
      to form complex self-assembled materials, and presents new sets of properties
      that are presently inconceivable for homogeneous or symmetrical dendrimers. Due
      to their unique features, JDs have a promising future in pharmaceutical and
      biomedical fields, as seen from the recent interest in their application in
      conjugating multiple drugs and targeting moieties, forming supramolecular
      hydrogels, enabling micellar delivery systems, and preparing nano-vesicles, known
      as dendrimersomes, for drug encapsulation. The present paper is the first review,
      with an emphasis on various emerging applications of JDs, in the drug delivery
      and biomedical field reported so far. In addition, the paper describes different
      synthetic methods for producing JDs that can guide the design of new
      biocompatible forms with pharmacological activities, and that have the potential
      to be nano drug delivery vehicles. Furthermore, future studies to optimize the
      applications of JDs in drug delivery sciences and biomedical field to realize
      their potential to treat various disease conditions are identified and
      highlighted. Overall, this review identifies the current status of JDs in terms
      of their synthesis and applications, as well as the future research for their
      translation into macromolecules for clinical applications to solve health
      problems. It highlights the future combined efforts needed to be taken by
      dendrimer chemists, formulation scientist and microbiologists to develop novel
      antibacterials and nanomedicines from JDs.

PMID- 27864065
TI  - Lateralization of splay posture in reticulated giraffe (Giraffa camelopardalis
      reticulate).
AB  - Motor laterality is quite often studied in non-human primates, but rarely has
      been investigated within ungulates. The aim of the study was to use the naturally
      occurring splay behavior in giraffe as a method to look for the presence of
      laterality. Four male giraffes housed at Zoo Atlanta were watched for three
      months, recording their first leg moved to begin the splay posture and the total
      number of leg movements to achieve a secure stance. All four giraffe
      significantly moved their left leg first to begin the stance, which suggests at
      least individual level laterality. However, using the number of leg movements
      overall, the last leg moved was only significant in one individual.

PMID- 27864066
TI  - Stimulus control in two rodent models of attention-deficit/hyperactivity
      disorder.
AB  - The spontaneously hypertensive (SHR/NCrl) rat from Charles River is one of the
      most widely used models of the combined subtype of Attention
      Deficit/Hyperactivity Disorder (ADHD-C). Although often used as its control
      strain, the Wistar Kyoto (WKY/NCrl) from Charles River has been proposed as a
      model of the predominately inattentive subtype of ADHD (ADHD-PI). In Experiment 1
      SHR/NCrl, WKY/NCrl, and Wistar (WI; the progenitor strain for the two models)
      rats were trained on a left->right lever-press sequence in the presence of light
      discriminative stimuli that signaled the active lever in the sequence. In
      subsequent conditions the discriminative light cues were removed or reversed.
      WKY/NCrl accuracy remained relatively stable across cue light transitions.
      SHR/NCrl and WI accuracy was more disrupted when light cues were removed or
      reversed-an indication that behavior of the WKY/NCrl rats may not have come under
      control of the discriminative light cues as it did for the other strains, but
      relied more on past behavior and spatial cues. In Experiment 2, all three strains
      were exposed to a response-initiated fixed-interval (RIFI) 8-s schedule of
      reinforcement. In RIFI schedules behavior must be timed from a past instance of
      the target response. Replicating previous work, timing during the FI was roughly
      equivalent across the three strains; however, latencies to initiate the FI were
      significantly longer for SHR/NCrl than WKY/NCrl and WI rats, suggesting SHR/NCrl
      behavior was less sensitive to the first-response:food contingency in the RIFI
      schedule. These findings identify differences in stimulus control between the
      three strains and may help determine the efficacy of SHR/NCrl and WKY/NCrl as
      models of ADHD subtypes in humans.

PMID- 27864067
TI  - "Better" clinical decisions do not necessarily require more time to make.

PMID- 27864068
TI  - Bibliographic study showed improving statistical methodology of network meta
      analyses published between 1999 and 2015.
AB  - OBJECTIVES: To assess the characteristics and core statistical methodology
      specific to network meta-analyses (NMAs) in clinical research articles. STUDY
      DESIGN AND SETTING: We searched MEDLINE, EMBASE, and the Cochrane Database of
      Systematic Reviews from inception until April 14, 2015, for NMAs of randomized
      controlled trials including at least four different interventions. Two reviewers
      independently screened potential studies, whereas data abstraction was performed
      by a single reviewer and verified by a second. RESULTS: A total of 456 NMAs,
      which included a median (interquartile range) of 21 (13-40) studies and 7 (5-9)
      treatment nodes, were assessed. A total of 125 NMAs (27%) were star networks;
      this proportion declined from 100% in 2005 to 19% in 2015 (P = 0.01 by test of
      trend). An increasing number of NMAs discussed transitivity or inconsistency (0%
      in 2005, 86% in 2015, P < 0.01) and 150 (45%) used appropriate methods to test
      for inconsistency (14% in 2006, 74% in 2015, P < 0.01). Heterogeneity was
      explored in 256 NMAs (56%), with no change over time (P = 0.10). All pairwise
      effects were reported in 234 NMAs (51%), with some increase over time (P = 0.02).
      The hierarchy of treatments was presented in 195 NMAs (43%), the probability of
      being best was most commonly reported (137 NMAs, 70%), but use of surface under
      the cumulative ranking curves increased steeply (0% in 2005, 33% in 2015, P <
      0.01). CONCLUSION: Many NMAs published in the medical literature have significant
      limitations in both the conduct and reporting of the statistical analysis and
      numerical results. The situation has, however, improved in recent years, in
      particular with respect to the evaluation of the underlying assumptions, but
      considerable room for further improvements remains.

PMID- 27864069
TI  - Microencapsulated SLN: An innovative strategy for pulmonary protein delivery.
AB  - Associating protein with nanoparticles is an interesting strategy to improve
      their bioavailability and biological activity. Solid lipid nanoparticles (SLN)
      have been sought as carriers for therapeutic proteins transport to the lung
      epithelium. Nevertheless, because of their low inertia, nanoparticles intended
      for pulmonary application usually escape from lung deposition. To overcome this
      problem, the production of spray-dried powders containing nanoparticles has been
      recently reported. Herein we developed new hybrid microencapsulated SLN for
      pulmonary administration, containing a model protein (papain, PAP). PAP was
      adsorbed onto glyceryl dibehenate and glyceryl tristearate SLN. Physical
      characterization using transmission electron microscopy (TEM), Fourier transform
      infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC)
      confirmed the interaction between PAP and SLN corroborating that the protein was
      efficiently adsorbed at SLN's surface. PAP adsorption onto SLN (PAP-SLN) slightly
      increased particle size, while decreasing the SLN negative surface charge. The
      adsorption process followed a Freundlich type of adsorption isotherm.
      Nanoformulations were then spray-dried, originating spherical microparticles with
      suitable aerodynamic characteristics. Full characterization of microparticles was
      performed using scanning electron microscopy (SEM), X-ray photoelectron
      spectroscopy (XPS) and isothermal titration calorimetry (ITC). PAP was released
      from dry powders in a higher extent when compared with non spray-dried SLN.
      Nevertheless, protein stability was kept throughout microsphere production, as
      assessed by SDS-PAGE.

PMID- 27864070
TI  - Friend or foe? The tumour microenvironment dilemma in colorectal cancer.
AB  - The network of bidirectional homotypic and heterotypic interactions established
      among parenchymal tumour cells and surrounding mesenchymal stromal cells
      generates the tumour microenvironment (TME). These intricate crosstalks elicit
      both beneficial and adverse effects on tumour initiation and progression
      unbalancing the signals and responses from the neighbouring cells. Here, we
      highlight the structure, activities and evolution of TME cells considering a
      novel colorectal cancer (CRC) classification based on differential stromal
      composition and gene expression profiles. In this scenario, we scrutinise the
      molecular pathways that either change or become corrupted during CRC development
      and their relative prognostic value. Finally, we survey the therapeutic molecules
      directed against TME components currently available in clinical trials as well as
      those with stronger potential in preclinical studies. Elucidation of dynamic
      variations in the CRC TME cell composition and their relative contribution could
      provide novel diagnostic or prognostic biomarkers and allow more personalised
      therapeutic strategies.

PMID- 27864071
TI  - Tetrahydroquinoline-based tricyclic amines as potent and selective agonists of
      the 5-HT2C receptor.
AB  - The syntheses, structure-activity relationships (SARs), and biological activities
      of tetrahydroquinoline-based tricyclic amines as 5-HT2C receptor agonists are
      reported. An early lead containing a highly unique 6,6,7-ring system was
      optimized for both in vitro potency and selectivity at the related 5-HT2B
      receptor. Orally bioactive, potent, and selective 6,6,6-tricyclic 5-HT2C agonists
      were identified.

PMID- 27864073
TI  - Eating behaviour of university students in Germany: Dietary intake, barriers to
      healthy eating and changes in eating behaviour since the time of matriculation.
AB  - A healthy diet plays a key role in preventing obesity and non-communicable
      diseases such as type 2 diabetes. This is true for all age groups, including
      young adults. While unhealthy eating habits among young adults, in particular
      university students, have been identified in former studies, this group has been
      neglected in existing health promotion strategies. Our aim was to explore
      baseline dietary intake, common barriers to healthy eating, and changes in eating
      behaviour among university students since the time of matriculation. We used data
      from the quantitative part of the Nutrition and Physical Activity Study (NuPhA),
      a cross-sectional online survey (data collection: 2014/10/31-2015/01/15).
      Students were recruited from all over Germany. Overall, 689 university students
      (30.5% male; mean age: 22.69) from more than 40 universities across Germany
      participated. We found that there is room for improvement with regard to the
      consumption of specific food groups, for example, fruits and vegetables. The main
      barriers to healthy eating were lack of time due to studies, lack of healthy
      meals at the university canteen, and high prices of healthy foods. Cluster
      analysis revealed that barriers to healthy eating might affect only specific
      subgroups, for instance freshmen. Changes in eating behaviour since matriculation
      were found in the consumption of meat, fish, and regular meals. Future
      qualitative studies may help to explore why university students change their
      eating behaviour since the time of matriculation. Such knowledge is necessary to
      inform health promotion strategies in the university setting.

PMID- 27864072
TI  - Racial and gender disparities in sugar consumption change efficacy among first
      year college students.
AB  - Reducing excess dietary sugar intake among emerging adults involves replacing
      sugar sweetened beverages (SSBs) and sugary snacks (SSN) with healthier options.
      Few studies have assessed the perceived degree of difficulty associated with
      making lifestyle modifications among a diverse group of emerging adults. The
      purpose of this study was to assess race and gender disparities in SSB and SSN
      behavioral modification efficacy among African American and White first year
      college students. A self-administered, cross-sectional survey was completed by a
      subsample of freshmen (n = 499) at a medium-sized southern university. Key
      outcome variables were self-efficacy in reducing consumption of SSBs and SSNs,
      respectively. Primary independent variables were BMI, concerns about weight, and
      attempts to lose weight, takeout food consumption frequency, and physical
      activity. Half of the sample was African American (50.1%) and a majority of
      participants were female (59.3%). Fewer African Americans than Whites were very
      sure they could substitute SSBs with water (48.8% vs 64.7%, p < 0.001) or eat
      fewer SSNs (39.2% vs 48.2%, p < 0.04). A smaller segment of males reported being
      confident in their ability replace SSBs with water (51.2% vs 60.5%, p < 0.04).
      African Americans (OR = 0.38, CI: 0.22-0.64) and males (OR = 0.49, CI: 0.27-0.88)
      had lower odds of being more confident in their ability to change their SSB
      intake. Race and gender differences were not present in models predicting
      confidence to reduce SSN consumption. These findings highlight the need to
      consider race and gender in interventions seeking to increase self-efficacy to
      make lifestyle modifications.

PMID- 27864074
TI  - Clinically isolated enterovirus A71 subgenogroup C4 strain with lethal
      pathogenicity in 14-day-old mice and the application as an EV-A71 mouse infection
      model.
AB  - The Enterovirus A71 (EV-A71) subgenogroup C4 is prevalent in China. EV-A71 causes
      hand, foot and mouth disease (HFMD) in children and may lead to severe
      neurological diseases. The development of antiviral and protective vaccines
      against EV-A71 is significantly hindered by the lack of suitable animal models to
      recapitulate human neurological symptoms. In this study, GZ-CII, a highly
      virulent EV-A71 subgenogroup C4 strain, was isolated from hospitalized children
      with HFMD. Intraperitoneal infections of GZ-CII resulted in progressive
      neurological disease in mice as old as 14 days. Administration of an inactivated
      EV-A71 vaccine or an anti-EV-A71 immune serum protected the mice against the GZ
      CII infection. This demonstrated that a mouse model with EV-A71 GZ-CII could be
      used to evaluate potential vaccine candidates and therapeutics for subgenogroup
      C4. Comparing the genome sequence of GZ-CII with that of the avirulent EV-A71
      subgenogroup C4 strain revealed unique mutations in GZ-CII. When mutation VP2
      K149I was introduced into the nonpathogenic EV-A71 subgenogroup C4 strain, the
      variant similar to GZ-CII significantly increased viral replication and virulence
      in mice. These results indicated that the VP2-K149I mutation played an important
      role in enhancing the virulence of the EV-A71 subgenogroup C4 strain in mice, and
      that mice infected with the GZ-CII strain are a promising model for evaluating
      vaccines and therapeutics against the EV-A71 subgenogroup C4.

PMID- 27864075
TI  - The natural compound silvestrol is a potent inhibitor of Ebola virus replication.
AB  - The DEAD-box RNA helicase eIF4A, which is part of the heterotrimeric translation
      initiation complex in eukaryotes, is an important novel drug target in cancer
      research because its helicase activity is required to unwind extended and highly
      structured 5'-UTRs of several proto-oncogenes. Silvestrol, a natural compound
      isolated from the plant Aglaia foveolata, is a highly efficient, non-toxic and
      specific inhibitor of eIF4A. Importantly, 5'-capped viral mRNAs often contain
      structured 5'-UTRs as well, which may suggest a dependence on eIF4A for their
      translation by the host protein synthesis machinery. In view of the recent Ebola
      virus (EBOV) outbreak in West Africa, the identification of potent antiviral
      compounds is urgently required. Since Ebola mRNAs are 5'-capped and harbor RNA
      secondary structures in their extended 5'-UTRs, we initiated a BSL4 study to
      analyze silvestrol in EBOV-infected Huh-7 cells and in primary human macrophages
      for its antiviral activity. We observed that silvestrol inhibits EBOV infection
      at low nanomolar concentrations, as inferred from large reductions of viral
      titers. This correlated with an almost complete disappearance of EBOV proteins,
      comparable in effect to the translational shutdown of expression of the proto
      oncoprotein PIM1, a cellular kinase known to be affected by silvestrol. Effective
      silvestrol concentrations were non-toxic in the tested cell systems. Thus,
      silvestrol appears to be a promising first-line drug for the treatment of acute
      EBOV and possibly other viral infections.

PMID- 27864076
TI  - Electric field as a potential directional cue in homing of bone marrow-derived
      mesenchymal stem cells to cutaneous wounds.
AB  - Bone marrow-derived cells are thought to participate and enhance the healing
      process contributing to skin cells or releasing regulatory cytokines. Directional
      cell migration in a weak direct current electric field (DC-EF), known as
      electrotaxis, may be a way of cell recruitment to the wound site. Here we
      examined the influence of electric field on bone marrow adherent cells (BMACs)
      and its potential role as a factor attracting mesenchymal stem cells to cutaneous
      wounds. We observed that in an external EF, BMAC movement was accelerated and
      highly directed with distinction of two cell populations migrating toward
      opposite poles: mesenchymal stem cells migrated toward the cathode, whereas
      macrophages toward the anode. Analysis of intracellular pathways revealed that
      macrophage electrotaxis mostly depended on Rho family small GTPases and calcium
      ions, but interruption of PI3K and Arp2/3 had the most pronounced effect on
      electrotaxis of MSCs. However, in all cases we observed only a partial decrease
      in directionality of cell movement after inhibition of certain proteins.
      Additionally, although we noticed the accumulation of EGFR at the cathodal side
      of MSCs, it was not involved in electrotaxis. Moreover, the cell reaction to EF
      was very dynamic with first symptoms occurring within <1min. In conclusion, the
      physiological DC-EF may act as a factor positioning bone marrow cells within a
      wound bed and the opposite direction of MSC and macrophage movement did not
      result either from utilizing different signalling or redistribution of
      investigated cell surface receptors.

PMID- 27864077
TI  - TRPV1 participates in the activation of clock molecular machinery in the brown
      adipose tissue in response to light-dark cycle.
AB  - Transient receptor potential (TRPs) channels are involved in thermogenesis, and
      temperature and energy balance control. Mice lacking TrpV1 become more obese and
      develop insulin resistance when fed with high fat diet; however, a relationship
      between metabolic disorders, TRP channels, and clock genes is still unknown.
      Based on this, we hypothesized that TRPV1 channels would be involved in the
      synchronization of clock genes in the peripheral tissues. To address this
      question, we used wild type (WT) and TrpV1 knockout (KO) mice kept in constant
      darkness (DD) or in light-dark cycle (LD). In WT mouse brown adipose tissue
      (BAT), TrpV1 oscillated with higher expression at scotophase, Per1 and Per2
      showed the same profile, and Bmal1 transcript only oscillated in DD.
      Interestingly, the oscillatory profile of these clock genes was abolished in
      TrpV1 KO mice. WT mouse Ucp1 was upregulated in LD as compared to DD, showing no
      temporal variation; mice lacking TrpV1 showed Ucp1 oscillation with a peak at the
      photophase. Remarkably, TrpV1 KO mice displayed less total activity than WT only
      when submitted to LD. We provide evidence that TRPV1 is an important modulator of
      BAT clock gene oscillations. Therefore, temperature and/or light-dependent
      regulation of TRPV1 activity might provide novel pharmacological approaches to
      treat metabolic disorders.

PMID- 27864078
TI  - Inappropriate translation inhibition and P-body formation cause cold-sensitivity
      in tryptophan-auxotroph yeast mutants.
AB  - In response to different adverse conditions, most eukaryotic organisms, including
      Saccharomyces cerevisiae, downregulate protein synthesis through the
      phosphorylation of eIF2alpha (eukaryotic initiation factor 2alpha) by Gcn2, a
      highly conserved protein kinase. Gcn2 also controls the translation of Gcn4, a
      transcription factor involved in the induction of amino acid biosynthesis
      enzymes. Here, we have studied the functional role of Gcn2 and Gcn2-regulating
      proteins, in controlling translation during temperature downshifts of TRP1 and
      trp1 yeast cells. Our results suggest that neither cold-instigated amino acid
      limitation nor Gcn2 are involved in the translation suppression at low
      temperature. However, loss of TRP1 causes increased eIF2alpha phosphorylation,
      Gcn2-dependent polysome disassembly and overactivity of Gcn4, which result in
      cold-sensitivity. Indeed, knock-out of GCN2 improves cold growth of trp1 cells.
      Likewise, mutation of several Gcn2-regulators and effectors results in cold
      growth effects. Remarkably, we found that Hog1, the osmoresponsive MAPK, plays a
      role in the regulatory mechanism of Gcn2-eIF2alpha. Finally, we demonstrated that
      P-body formation responds to a downshift in temperature in a TRP1-dependent
      manner and is required for cold tolerance.

PMID- 27864079
TI  - Temporal reliability of ultra-high field resting-state MRI for single-subject
      sensorimotor and language mapping.
AB  - Resting-state fMRI is a well-suited technique to map functional networks in the
      brain because unlike task-based approaches it requires little collaboration from
      subjects. This is especially relevant in clinical settings where a number of
      subjects cannot comply with task demands. Previous studies using conventional
      scanner fields have shown that resting-state fMRI is able to map functional
      networks in single subjects, albeit with moderate temporal reliability. Ultra
      high resolution (7T) imaging provides higher signal-to-noise ratio and better
      spatial resolution and is thus well suited to assess the temporal reliability of
      mapping results, and to determine if resting-state fMRI can be applied in
      clinical decision making including preoperative planning. We used resting-state
      fMRI at ultra-high resolution to examine whether the sensorimotor and language
      networks are reliable over time - same session and one week after. Resting-state
      networks were identified for all subjects and sessions with good accuracy. Both
      networks were well delimited within classical regions of interest. Mapping was
      temporally reliable at short and medium time-scales as demonstrated by high
      values of overlap in the same session and one week after for both networks.
      Results were stable independently of data quality metrics and physiological
      variables. Taken together, these findings provide strong support for the
      suitability of ultra-high field resting-state fMRI mapping at the single-subject
      level.

PMID- 27864080
TI  - Alterations of resting state functional network connectivity in the brain of
      nicotine and alcohol users.
AB  - Alcohol and nicotine intake result in neurological alterations at the circuit
      level. Resting state functional connectivity has shown great potential in
      identifying these alterations. However, current studies focus on specific seeds
      and leave out many brain regions where effects might exist. The present study
      uses a data driven technique for brain segmentation covering the whole brain.
      Functional magnetic-resonance-imaging (fMRI) data were collected from 188
      subjects:51 non-substance consumption controls (CTR), 36 smoking-and-drinking
      subjects (SAD), 28 drinkers (DRN), and 73 smokers (SMK). Data were processed
      using group independent component analysis to derive resting state networks
      (RSN). The resting state functional network connectivity (rsFNC) was then
      calculated through correlation between time courses. One-way ANOVA tests were
      used to detect rsFNC differences among the four groups. A total of 50 ANOVA tests
      were significant after multi-comparison correction. Results delineate a general
      pattern of hypo-connectivity in the substance consumers. Precuneus, postcentral
      gyrus, insula and visual cortex were the main brain areas with rsFNC reduction
      suggesting reduced interoceptive awareness in drinkers. In addition, connectivity
      reduction between postcentral and one RSN covering right fusiform and lingual
      gyri showed significant association with severity of hazardous drinking. In
      smokers, connectivity changes agreed with the idea of a shift towards endogenous
      information processing, represented by the DMN. Hypo-connectivity between
      thalamus and putamen was observed in smokers. In contrast, the angular gyrus
      showed hyper-connectivity with the precuneus linked to smoking and significantly
      correlated with nicotine dependence severity. In spite of the presence of common
      effects, our results suggest that particular effects of alcohol and nicotine can
      be separated and identified. Results also suggest that concurrent use of both
      substances affects brain connectivity in a complex manner, requiring careful
      consideration of interaction effects.

PMID- 27864082
TI  - Individual variation in intentionality in the mind-wandering state is reflected
      in the integration of the default-mode, fronto-parietal, and limbic networks.
AB  - Mind-wandering has a controversial relationship with cognitive control. Existing
      psychological evidence supports the hypothesis that episodes of mind-wandering
      reflect a failure to constrain thinking to task-relevant material, as well the
      apparently alternative view that control can facilitate the expression of self
      generated mental content. We assessed whether this apparent contradiction arises
      because of a failure to consider differences in the types of thoughts that occur
      during mind-wandering, and in particular, the associated level of intentionality.
      Using multi-modal magnetic resonance imaging (MRI) analysis, we examined the
      cortical organisation that underlies inter-individual differences in descriptions
      of the spontaneous or deliberate nature of mind-wandering. Cortical thickness, as
      well as functional connectivity analyses, implicated regions relevant to
      cognitive control and regions of the default-mode network for individuals who
      reported high rates of deliberate mind-wandering. In contrast, higher reports of
      spontaneous mind-wandering were associated with cortical thinning in parietal and
      posterior temporal regions in the left hemisphere (which are important in the
      control of cognition and attention) as well as heightened connectivity between
      the intraparietal sulcus and a region that spanned limbic and default-mode
      regions in the ventral inferior frontal gyrus. Finally, we observed a
      dissociation in the thickness of the retrosplenial cortex/lingual gyrus, with
      higher reports of spontaneous mind-wandering being associated with thickening in
      the left hemisphere, and higher repots of deliberate mind-wandering with thinning
      in the right hemisphere. These results suggest that the intentionality of the
      mind-wandering state depends on integration between the control and default-mode
      networks, with more deliberation being associated with greater integration
      between these systems. We conclude that one reason why mind-wandering has a
      controversial relationship with control is because it depends on whether the
      thoughts emerge in a deliberate or spontaneous fashion.

PMID- 27864081
TI  - Genetic and environmental influences on cortical mean diffusivity.
AB  - Magnetic resonance imaging (MRI) has become an important tool in the early
      detection of age-related and neuropathological brain changes. Recent studies
      suggest that changes in mean diffusivity (MD) of cortical gray matter derived
      from diffusion MRI scans may be useful in detecting early effects of Alzheimer's
      disease (AD), and that these changes may be detected earlier than alterations
      associated with standard structural MRI measures such as cortical thickness.
      Thus, due to its potential clinical relevance, we examined the genetic and
      environmental influences on cortical MD in middle-aged men to provide support for
      the biological relevance of this measure and to guide future gene association
      studies. It is not clear whether individual differences in cortical MD reflect
      neuroanatomical variability similarly detected by other MRI measures, or whether
      unique features are captured. For instance, variability in cortical MD may
      reflect morphological variability more commonly measured by cortical thickness.
      Differences among individuals in cortical MD may also arise from breakdowns in
      myelinated fibers running through the cortical mantle. Thus, we investigated
      whether genetic influences on variation in cortical MD are the same or different
      from those influencing cortical thickness and MD of white matter (WM) subjacent
      to the cortical ribbon. Univariate twin analyses indicated that cortical MD is
      heritable in the majority of brain regions; the average of regional heritability
      estimates ranged from 0.38 in the cingulate cortex to 0.66 in the occipital
      cortex, consistent with the heritability of other MRI measures of the brain.
      Trivariate analyses found that, while there was some shared genetic variance
      between cortical MD and each of the other two measures, this overlap was not
      complete (i.e., the correlation was statistically different from 1). A
      significant amount of distinct genetic variance influences inter-individual
      variability in cortical MD; therefore, this measure could be useful for further
      investigation in studies of neurodegenerative diseases and gene association
      studies.

PMID- 27864083
TI  - Robust skull stripping using multiple MR image contrasts insensitive to
      pathology.
AB  - Automatic skull-stripping or brain extraction of magnetic resonance (MR) images
      is often a fundamental step in many neuroimage processing pipelines. The accuracy
      of subsequent image processing relies on the accuracy of the skull-stripping.
      Although many automated stripping methods have been proposed in the past, it is
      still an active area of research particularly in the context of brain pathology.
      Most stripping methods are validated on T1-w MR images of normal brains,
      especially because high resolution T1-w sequences are widely acquired and ground
      truth manual brain mask segmentations are publicly available for normal brains.
      However, different MR acquisition protocols can provide complementary information
      about the brain tissues, which can be exploited for better distinction between
      brain, cerebrospinal fluid, and unwanted tissues such as skull, dura, marrow, or
      fat. This is especially true in the presence of pathology, where hemorrhages or
      other types of lesions can have similar intensities as skull in a T1-w image. In
      this paper, we propose a sparse patch based Multi-cONtrast brain STRipping method
      (MONSTR),2 where non-local patch information from one or more atlases, which
      contain multiple MR sequences and reference delineations of brain masks, are
      combined to generate a target brain mask. We compared MONSTR with four state-of
      the-art, publicly available methods: BEaST, SPECTRE, ROBEX, and OptiBET. We
      evaluated the performance of these methods on 6 datasets consisting of both
      healthy subjects and patients with various pathologies. Three datasets (ADNI,
      MRBrainS, NAMIC) are publicly available, consisting of 44 healthy volunteers and
      10 patients with schizophrenia. Other three in-house datasets, comprising 87
      subjects in total, consisted of patients with mild to severe traumatic brain
      injury, brain tumors, and various movement disorders. A combination of T1-w, T2-w
      were used to skull-strip these datasets. We show significant improvement in
      stripping over the competing methods on both healthy and pathological brains. We
      also show that our multi-contrast framework is robust and maintains accurate
      performance across different types of acquisitions and scanners, even when using
      normal brains as atlases to strip pathological brains, demonstrating that our
      algorithm is applicable even when reference segmentations of pathological brains
      are not available to be used as atlases.

PMID- 27864085
TI  - Single cell screening approaches for antibody discovery.
AB  - Microtools that have been developed to allow in depth interrogation of individual
      cells in high throughput are improving our understanding of biological processes
      at the single cell level and are opening up new possibilities for biological
      research. In relation to antibody discovery, these tools are now helping to
      maximise the full potential of well-established methodologies for antibody
      generation. Being complementary to both recombinant and native antibody secreting
      cells, some of these tools are finding widespread use in the field. In this
      review, we discuss how microtools for single cell analysis are addressing some of
      the limitations of traditional approaches for antibody screening. We describe the
      main classes of microtools for antibody discovery along with a comparison of each
      technology and an outlook for the future utility of some of these microtools for
      discovery and research.

PMID- 27864086
TI  - Targeted memory reactivation of newly learned words during sleep triggers REM
      mediated integration of new memories and existing knowledge.
AB  - Recent memories are spontaneously reactivated during sleep, leading to their
      gradual strengthening. Whether reactivation also mediates the integration of new
      memories with existing knowledge is unknown. We used targeted memory reactivation
      (TMR) during slow-wave sleep (SWS) to selectively cue reactivation of newly
      learned spoken words. While integration of new words into their phonological
      neighbourhood was observed in both cued and uncued words after sleep, TMR
      triggered integration was predicted by the time spent in rapid eye movement (REM)
      sleep. These data support complementary roles for SWS and REM in memory
      consolidation.

PMID- 27864088
TI  - Modality-invariant audio-visual association coding in crow endbrain neurons.
AB  - Single neuron activity in the corvid nidopallium caudolaterale (NCL), the
      supposed avian functional analog of the prefrontal cortex, represents
      associations of auditory with visual stimuli. This is of high adaptive value for
      songbirds that need to rely on audio-visual associations to communicate, find a
      mate or escape predators. However, it remains unclear whether NCL neurons can
      represent cross-modal associations in a modality invariant, abstract fashion. To
      dissociate between modality-dependent and modality-invariant NCL activity, we
      trained two crows to match auditory sample cues with visual test stimuli, and
      vice versa, across a temporal memory delay. During sample presentation, NCL
      activity selectively encoded associations in a modality invariant fashion. During
      the delay, we observed subject specific, population-level coding biases in NCL
      activity. Despite of these biases, task relevant information could be decoded
      equally well from either subject's neuronal delay activity. Decoding success was
      facilitated by many mixed selectivity neurons, which mediated high dimensional
      representations of task variables on the NCL population level. These results
      parallel findings from the mammalian PFC, suggesting common mechanisms
      responsible for the adaptability of multimodal association areas across taxa.

PMID- 27864087
TI  - Setting the occasion for adolescent inhibitory control.
AB  - During adolescence, individuals experience a broad range of dynamic environments
      as they strive to establish independence. Learning to respond appropriately in
      both new and previously encountered environments requires that an individual
      identify and learn the meaning of cues indicating that a behavior is appropriate,
      or alternatively, that it should be altered or inhibited. Although the ability to
      regulate goal-directed behavior continues to develop across adolescence, the
      specific circumstances under which adolescents experience difficulty with
      inhibitory control remain unclear. Here we review recent findings in our
      laboratory that address how adolescents learn to proactively inhibit a response.
      Much of our research has utilized a negative occasion setting paradigm, in which
      one cue (a feature) gates the meaning of a second cue (a target). The feature
      provides information that resolves the ambiguity of the target and indicates the
      appropriate behavioral response to the target. As such, we have been able to
      determine how adolescents learn about ambiguous stimuli, such as those whose
      meaning changes in accordance with other features of the surrounding environment.
      We consider why adolescents in particular exhibit difficulty in negative occasion
      setting compared to either pre-adolescents or adults. In addition, we review
      findings indicating that a balance in neural activity between orbitofrontal
      cortex and nucleus accumbens is necessary to support normal negative occasion
      setting. Finally, we consider aspects of associative learning that may contribute
      to adolescent inhibitory control, as well as provide insight into adolescent
      behavior as a whole.

PMID- 27864090
TI  - Prevalence of food allergies in South Asia.
AB  - OBJECTIVE: To evaluate the published medical literature on the prevalence and
      types of food allergies in South Asia. DATA SOURCES: A PubMed search was
      performed using the keywords India and food allergy, Asia and food allergy, and
      South Asia and food allergy for any period. Articles cited in selected studies
      were reviewed for their appropriateness of inclusion into this review. STUDY
      SELECTIONS: Publications were included that were original research and fit the
      topic of food allergy and South Asia. South Asia is defined as region inclusive
      of India, Pakistan, Bangladesh, and Sri Lanka. RESULTS: A total of 169 articles
      were initially identified, and 47 were reviewed in detail for inclusion in this
      review. The primary focus was placed on 10 studies that consisted of case reports
      of newly reported or documented food allergy, survey studies that investigated
      food allergy prevalence in specific demographics, and prospective and cross
      sectional studies with case controls, all of which investigated food allergy
      prevalence by allergy testing in a selected population. CONCLUSION: The medical
      literature on the prevalence and types of food allergy in South Asia indicates
      that there is a variety of unusual and unique allergens and an overall low
      incidence of food allergy. There is also an association of increased food allergy
      prevalence in individuals who live in metropolitan regions or who migrate to
      communities that have adopted westernization.

PMID- 27864089
TI  - Anaphylaxis induced by ingested molds.

PMID- 27864091
TI  - Diurnal variations in subcutaneous allergen immunotherapy reactions.
AB  - BACKGROUND: Circadian rhythms underlie many immune responses and allergic
      diseases. Subcutaneous immunotherapy (SCIT) can result in adverse reactions;
      however, it is unclear whether such reactions have a diurnal pattern. OBJECTIVE:
      To assess whether the timing of SCIT affects the rate of adverse reactions.
      METHODS: This study was a retrospective medical record review of adult patients
      (n = 289) who received SCIT at the Northwestern Medical Faculty Foundation,
      Chicago, Illinois, during a 10-year period (2004-2014). Injections were given in
      the outpatient setting. There were a total of 17,457 injections with 574
      reactions. Covariates included age, sex, median income, asthma status, vial
      contents, number of injections, and previous immunotherapy reactions. Logistical
      regression was used to calculate the odds of having a reaction with time of SCIT
      administration as the primary determinate. RESULTS: Immunotherapy reactions
      occurred more frequently after afternoon or evening (pm) injections (328/8721 =
      3.8%) vs morning (am) injections (246/8736 = 2.8%), (chi2 = 12.26, P < .01).
      Systemic reactions, defined as World Allergy Organization grade 1 or higher, did
      not have diurnal variation (59/8721 = 0.67% for pm vs am 56/8736 = 0.64% for
      morning; chi2 = 0.08; P = .77). pm injections resulted in higher odds of reaction
      compared with am injection in a fully adjusted logistic regression model (odds
      ratio = 1.43; 95% confidence interval, 1.20-1.70; P < .01). When considering time
      as 4 categories, the highest odds of reaction were noted for the period from
      15:01 to 17:30 (odds ratio, 1.55; 95% confidence interval, 1.21-2.00; P < .01).
      CONCLUSION: pm injections of SCIT are associated with increased cutaneous
      reaction rates when compared with am injections. In patients experiencing
      bothersome local reactions, it may be beneficial to administer SCIT in the
      morning.

PMID- 27864084
TI  - Development and regeneration of vestibular hair cells in mammals.
AB  - Vestibular sensation is essential for gaze stabilization, balance, and perception
      of gravity. The vestibular receptors in mammals, Type I and Type II hair cells,
      are located in five small organs in the inner ear. Damage to hair cells and their
      innervating neurons can cause crippling symptoms such as vertigo, visual field
      oscillation, and imbalance. In adult rodents, some Type II hair cells are
      regenerated and become re-innervated after damage, presenting opportunities for
      restoring vestibular function after hair cell damage. This article reviews
      features of vestibular sensory cells in mammals, including their basic
      properties, how they develop, and how they are replaced after damage. We discuss
      molecules that control vestibular hair cell regeneration and highlight areas in
      which our understanding of development and regeneration needs to be deepened.

PMID- 27864092
TI  - Successful desensitization to natalizumab using a 1-solution protocol.

PMID- 27864093
TI  - Skin testing and drug challenge outcomes in antibiotic-allergic patients with
      immediate-type hypersensitivity.
AB  - BACKGROUND: The evaluation of antibiotic immediate-type hypersensitivity is
      intricate because of nonstandardized skin testing and challenge method
      variability. OBJECTIVE: To determine the safety outcomes and risk factors for
      antibiotic challenge reactions in patients reporting a history of antibiotic
      immediate-type hypersensitivity. METHODS: A 5-year retrospective review of
      patients evaluated for immediate-type antibiotic allergy was conducted. Data
      analyzed included patient demographics, index reaction details, and outcomes of
      skin testing and challenges, classified as single-step or multistep. RESULTS:
      Antibiotic hypersensitivity history was identified in 211 patients: 78% to
      penicillins, 10% to fluoroquinolones, 7.6% to cephalosporins, and 3.8% to
      carbapenems. In total, 179 patients completed the challenges (median age 67
      years, range 50-76 years, 56% women), and compared with nonchallenged patients,
      they reported nonanaphylactic (P < .001) and remote index (P = .003) reactions.
      Sixteen patients (8.9%) experienced challenge reactions (5 of 28 for single-step
      challenge, 11 of 151 for multistep challenge), and 11 of these patients had
      negative skin testing results before the challenge. Challenge-reactive patients
      were significantly younger (P = .007), more often women (P = .036), and had
      additional reported antibiotic allergies (P = .005). No correlation was detected
      between the reported index and observed challenge reaction severities (kappa = 
      0.05, 95% confidence interval -0.34 to 0.24). Anaphylactic rates were similar
      during single-step and multistep challenges (3.6% vs 3.3%). CONCLUSION: In the
      present population, younger women with multiple reported antibiotic allergies
      were at greatest risk for challenge reactions. Negative skin testing results did
      not exclude reactions, and index severity was not predictive of challenge
      outcome. The multistep and full-dose methods demonstrated a comparable reaction
      risk for anaphylaxis.

PMID- 27864095
TI  - Optimization of an in vitro chemotherapy to avoid resistant tumours.
AB  - Chemotherapy use against solid tumours often results in the resistance of the
      cancer cells to the molecule used. In this paper, we will set up and analyse an
      ODE model for heterogeneous in vitro tumours, consisting of cells that are
      sensitive or resistant to a certain drug. We will then use this model to develop
      different protocols, that aim at reducing the tumour volume while preserving its
      heterogeneity. These drug administration schedules are determined through
      analysis of the system dynamics, and optimal control theory.

PMID- 27864096
TI  - Effects of initial telomere length distribution on senescence onset and
      heterogeneity.
AB  - Replicative senescence, induced by telomere shortening, exhibits considerable
      asynchrony and heterogeneity, the origins of which remain unclear. Here, we
      formally study how telomere shortening mechanisms impact on senescence kinetics
      and define two regimes of senescence, depending on the initial telomere length
      variance. We provide analytical solutions to the model, highlighting a non-linear
      relationship between senescence onset and initial telomere length distribution.
      This study reveals the complexity of the collective behavior of telomeres as they
      shorten, leading to senescence heterogeneity.

PMID- 27864097
TI  - Post-translational regulation by structural changes of 4-dihydromethyltrisporate
      dehydrogenase, a key enzyme in sexual and parasitic communication mediated by the
      trisporic acid pheromone system, of the fungal fusion parasite Parasitella
      parasitica.
AB  - Sexual communication between complementary mating partners in the fungal group of
      zygomycetes is mediated by the trisporoid pheromone system. A key enzyme towards
      biosynthesis of hormonally active trisporoids is 4-dihydromethyltrisporate
      dehydrogenase (TSP1), an enzyme occurring in all zygomycetous fungi. Trisporic
      acid and some of its precursor molecules serve as pheromones for recognizing
      complementary mating partners and for induction of the differentiation program
      towards sexual spore formation. In the parasitic zygomycete Parasitella
      parasitica, a biotrophic fusion parasite infecting many other zygomycetes, these
      substances have an additional function: They are also responsible for host
      parasite recognition and the formation of the characteristic infection
      structures. Parasitic interactions are mating type dependent as well. In the
      Mucor-related mycoparasite P. parasitica we can study both types of communication
      in parallel. We were interested in protein structures of TSP1 from P. parasitica,
      the genome of which was recently sequenced by us, and especially in the
      mechanisms involved in the switch from sexual to parasitic communication. P.
      parasitica contains at least six genes coding for TSP1-like proteins. We created
      models of tertiary structures and performed protein-protein docking with the
      resulting protein structures to simulate dimerization and to provide support for
      probable regulatory mechanisms at the protein level. The resulting structure
      models show differences in putative activity and binding preferences between the
      different TSP1-like proteins. Two of them seem to be able to form solid binding
      pockets for substrate and cosubstrate after dimerization. The other four TSP1
      like proteins are more likely to represent regulating subunits for the two active
      isoforms. The ability to form homodimers with enzymatic activity could be the
      crucial difference between sexual and parasitic communication pathways. TSP1
      PARPA_07791 forms enzymatically inactive homodimers. The second TSP1,
      PARPA_04105, forms active homodimers and could be responsible for the parasitic
      pathway of communication. Both TSP1 proteins can form more or less active
      heterodimers with the additional TSP1-like proteins. TSP1 PARPA_07791 mediates
      the sexual pathway probably as in other zygomycetous fungi like Mucor mucedo.
      High sequence identities between this TSP1 isomer and TSP1 proteins from other
      zygomycetes substantiate its function. This bioinformatic study supports previous
      experimental findings of post-translational regulation of 4
      dihydromethyltrisporate dehydrogenases in zygomycetes and, for the first time,
      provides a substantiated hypothesis of the underlying mechanism.

PMID- 27864094
TI  - Sternopygus macrurus electric organ transcriptome and cell size exhibit
      insensitivity to short-term electrical inactivity.
AB  - Electrical activity is an important regulator of cellular function and gene
      expression in electrically excitable cell types. In the weakly electric teleost
      fish Sternopygus macrurus, electrocytes, i.e., the current-producing cells of the
      electric organ, derive from a striated muscle lineage. Mature electrocytes are
      larger than muscle fibers, do not contain sarcomeres, and are driven continuously
      at frequencies higher than those exerted on muscle cells. Previous work showed
      that the removal of electrical activity by spinal cord transection (ST) for two
      and five weeks led to an upregulation of some sarcomeric proteins and a decrease
      in electrocyte size. To test whether changes in gene transcription preceded these
      phenotypic changes, we determined the sensitivity of electrocyte gene expression
      to electrical inactivity periods of two and five days after ST. Whole tissue gene
      expression profiles using deep RNA sequencing showed minimal alterations in the
      levels of myogenic transcription factor and sarcomeric transcripts after either
      ST period. Moreover, while analysis of differentially expressed genes showed a
      transient upregulation of genes associated with proteolytic mechanisms at two
      days and an increase in mRNA levels of cytoskeletal genes at five days after
      electrical silencing, electrocyte size was not affected. Electrical inactivity
      also resulted in the downregulation of genes that were classified into enriched
      clusters associated with functions of axon migration and synapse structure.
      Overall, these data demonstrate that unlike tissues in the myogenic lineage in
      other vertebrate species, regulation of gene transcription and cell size in the
      muscle-like electrocytes of S. macrurus is highly insensitive to short-term
      electrical inactivity. Moreover, together with data obtained from control and
      long-term ST studies, the present data suggest that neural input might influence
      post-transcriptional processes to affect the mature electrocyte phenotype.

PMID- 27864098
TI  - Screening for mucopolysaccharidoses in the Turkish population: Analytical and
      clinical performance of an age-range specific, dye-based, urinary
      glycosaminoglycan assay.
AB  - Comprehensive analytical and diagnostic performance of urinary quantitative GAG
      analysis with dimethylmethylene blue (DMB) and the age-specific reference ranges
      were determined in Turkish population, which has a high incidence of MPSs.
      Precision, linearity, recovery and accuracy/trueness, limits, stability, and
      effect of interferents were tested according to CLSI guideline. Clinical
      performance was evaluated with ROC analyses including 45 MPS patients. Intra-day
      and inter-day precisions were <5% and <11% (CV), respectively. LoD was 9.12mg/L
      and LoQ was 23.3mg/L. The highest reference values for urinary GAG excretion were
      determined in an age-specific manner. In the 2-13years age cohort, a cut-off of
      89.86mg/g creatinine resulted in 98.07% sensitivity and 93.33% specificity.
      Proteinuria and hematuria interfered with analysis in some instances. Neither
      leukocyturia nor pH changes affected the assay. Stability analysis indicated that
      freezing urine samples for transfer is unnecessary. Of the 45 MPS patient samples
      evaluated, only three tested negative including MPS II, IVA and VI. Despite
      limitations due to low levels of urinary GAG excretion in some cases, urinary GAG
      analysis with DMB with its technical simplicity, low cost, and precise
      quantitative results, is a valuable screening method, particularly in populations
      with a high rate of MPSs.

PMID- 27864099
TI  - Comparability of the effect of storage time and temperature on serum anti
      Mullerian hormone measurement between original and modified enzyme-linked
      immunosorbent assay.
AB  - OBJECTIVE: To explore the effect of modified enzyme-linked immunosorbent assay on
      the AMH results is increased or decreased, and to investigate the effect of
      storage time and temperature on AMH measurements with and without sample
      premixing assay buffer using the Kangrun ELISA method. METHOD: Serum AMH
      concentration were measured by ELISA, consistency between two kits, and
      comparability between original and the modified assay under different stored
      conditions were analyzed by Passing-Bablok regression analysis and Bland-Altman
      bias evaluation. RESULT: There was a strong consistency between AMH
      concentrations measured in Kangrun ELISA and Ansh Labs ultra-sensitive AMH ELISA.
      Pre-mixing serum specimens with assay buffer gave consistent results compared
      with original assay. Modified protocol can reduce the amplitude of increase
      affected by sample aged and give the most consistent results regardless of
      storage conditions. CONCLUSION: Pre-mixing protocol did not influence the results
      of fresh serum or frozen serum incubation <3days at 4 degrees C and -80 degrees
      C, but when specimens detected after collection and stored in other storage
      conditions, should be pre-mixed with assay buffer to insure its accuracy.

PMID- 27864100
TI  - Clinical relevance of combined anti-mitochondrial M2 detection assays for primary
      biliary cirrhosis.
AB  - BACKGROUND: Antimitochondrial antibody (AMA) is a specific serologic marker in
      primary biliary cirrhosis (PBC). The aim of this study was to evaluate the
      clinical relevance of combined AMA assays. METHODS: Sera were obtained from 79
      patients with PBC and 108 patients with other liver disease. They were tested by
      indirect immunofluorescence (IIF) using rat kidney/stomach tissue and HEp2 cells
      as substrate, 4 AMA-M2 assays, anti-sp100, and anti-gp210 assays. RESULTS: Using
      IIF-AMA with cut-off titer of 1:40, the sensitivity and specificity for PBC were
      88.6% and 87.0%, respectively. A cut-off titer of 1:80 improved the specificity
      to 93.5%. The 4 commercial assay kits using AMA-M2 autoantibodies showed
      sensitivity of 55.7-79.7% and specificity of 91.7-95.4% with moderate to good
      agreement. AMA-M2 assays using both native and recombinant E2 antigens had higher
      sensitivity. ANAs on HEp2 cells, anti-sp100, and anti-gp210 were detected in
      67.1%, 13.9-15.2%, and 22.8-27.8% of PBC patients, respectively. Additional AMA
      M2 specific assays in IIF-AMA negative and low titer positive (1:40) sera
      increased the sensitivity and specificity to 88.6% and 90.7%, respectively.
      CONCLUSIONS: Serological diagnosis for PBC using IIF with high titer cut-off and
      additional AMA-M2 specific tests by ELISA or LIA in IIF-negative sera should be
      used.

PMID- 27864101
TI  - Targeted exome sequencing identifies novel compound heterozygous mutations in
      P3H1 in a fetus with osteogenesis imperfecta type VIII.
AB  - Osteogenesis imperfecta (OI) is a highly clinically and genetically heterogeneous
      group of disorders. It is difficult to identify severe OI in the perinatal
      period. Here, a Chinese woman with a suspected history of fetal OI was referred
      to our institution at 19weeks of gestation, due to ultrasound inspection during
      antenatal screening, which revealed bulbous metaphyses, short humeri, and short
      thick bent femora in the fetus. Using targeted exome sequencing of 248 genes
      known to be involved in skeletal system diseases, we identified novel compound
      heterozygous mutation in the P3H1 gene in the fetus with OI type VIII:
      c.105_120del (p.D36Rfs*16) and c.2164C>T (p.Q722*). These two mutations were
      inherited from the father and mother, respectively. The mRNA level of P3H1 wasn't
      changed suggested that mRNA with this mutation escaped from nonsense-mediated RNA
      decay. Besides, the level of P3H1 was absence while the CRTAP was mildly
      decreased. In conclusion, our findings imply this novel compound heterozygous
      mutation as the molecular pathogenetic in a Chinese fetus with OI type VIII, and
      demonstrate that targeted next-generation sequencing (NGS) is an accurate, rapid,
      and cost-effective method in the genetic diagnosis of fetal skeletal dysplasia
      with genetic and clinical heterogeneity, especially for autosomal recessive
      skeletal disorders.

PMID- 27864102
TI  - A health sciences student-run smoking cessation clinic experience within a
      homeless population.
AB  - OBJECTIVE: The primary objective is to describe a professional and graduate
      student-run approach to smoking cessation education combined with motivational
      interviewing and pharmacotherapy in regard to the frequency of follow-up with a
      smoking cessation quitline program in the homeless population. The secondary
      objective is to assess participants' self-reported level of confidence,
      knowledge, and willingness to quit before and after participation in the student
      run smoking cessation clinic. SETTING: Homeless shelter in Phoenix, Arizona.
      PRACTICE DESCRIPTION: A previously established professional and graduate student
      led clinic focused on providing a wide variety of free health services to
      homeless populations at a homeless shelter. One service not offered was smoking
      cessation support; thus, a student-run smoking cessation clinic was established.
      PRACTICE INNOVATION: Patients were provided smoking cessation education,
      motivational interviewing, and pharmacotherapy by health sciences professional
      and graduate students. Patients were then given a 2-week supply of nicotine
      replacement therapy and referred to the state's smoking cessation quitline. The
      impact of multiple concomitant smoking cessation strategies provided by students
      within a homeless population has not been studied previously. EVALUATION: A 10
      day post-referral status update on the success of contact with patients was
      provided to study investigators from the smoking cessation quitline. Surveys were
      also used to assess the patient's self-reported level of perceived benefit with
      the student-run smoking cessation clinic. RESULTS: Of the 139 unique patients, 19
      (13.7%) successfully contacted the smoking cessation quitline. Patients reported
      high baseline confidence, knowledge, and willingness related to quit attempts;
      they reported a small improvement in reported values after participation in the
      student-run clinics. CONCLUSION: In the homeless population, smoking cessation
      education, motivational interviewing, and pharmacotherapy had a low follow-up
      frequency with a smoking cessation quitline, but slightly increased the patient's
      confidence, knowledge, and willingness to quit.

PMID- 27864103
TI  - Beneficial effect of coenzyme Q10 injection on nitric oxide -related dilation of
      the rat aorta.
AB  - This study examined whether coenzyme Q10 can improve nitric oxide (NO)-dependent
      vasodilatation in the rat aorta after pre-incubation or intravenous
      administration. In initial experiments, intact isolated aortic rings were
      incubated with coenzyme Q10 or L-arginine. In further experiments, coenzyme Q10
      was administered intravenously in anesthetized rats, then in 2h aorta was
      isolated. In both cases, after preliminary preparation the isolated aortic rings
      were tested for acetylcholine-induced NO-dependent relaxation. Acetylcholine
      elicited concentration-dependent relaxation of phenylephine precontracted aortic
      rings. Relaxant responses to acetylcholine were markedly potentiated after pre
      incubation with coenzyme Q10 or L-arginine. The maximum relaxant responses (%)
      were significantly increased from 64.1+/-5.3 (control) to 89.8+/-3.0 and 83.6+/
      3.0 (coenzyme Q10 and L-arginine, respectively). pD2 (-lgEC50) value in control
      study was 5.81+/-0.28, after pretreatment with coenzyme Q10 or L-arginine were
      7.59+/-0.16 and 7.26+/-0.32, respectively. There was no difference between
      coenzyme Q10 and L-arginine groups. After intravenous administration, the
      relaxant responses to acetylcholine were significantly increased in coenzyme Q10
      treated group (94.2+/-2.0) compared with controls (68.1+/-4.4). pD2 values were
      also different between control and treatment groups (5.79+/-0.29 vs. 8.14+/-0.65,
      respectively). Thus, coenzyme Q10 improved NO-mediated vasodilation in rat aorta
      in magnitude close to the effects of L-arginine - substrate for eNOS. Our data
      first show that exogenous coenzyme Q10 through intravenous administration is able
      to improve rapidly NO-dependent vasodilation in rat aorta, likely due to
      accumulation of coenzyme Q10 in the vessel wall. Improvement of endothelial
      function can contribute, at least in part, to beneficial effects of coenzyme Q10
      in cardiovascular diseases associated with endothelial dysfunction.

PMID- 27864104
TI  - Pharmacological response sensitization in nerve cell networks exposed to the
      antibiotic gentamicin.
AB  - Gentamicin is an aminoglycoside antibiotic that is used in clinical, organismic,
      and agricultural applications to combat gram-negative, aerobic bacteria. The
      clinical use of gentamicin is widely linked to various toxicities, but there is a
      void in our knowledge about the neuromodulatory or neurotoxicity effects of
      gentamicin. This investigation explored the electrophysiologic effects of
      gentamicin on GABAergic pharmacological profiles in spontaneously active neuronal
      networks in vitro derived from auditory cortices of E16 mouse embryos and grown
      on microelectrode arrays. Using the GABAA agonist muscimol as the test substance,
      responses from networks to dose titrations of muscimol were compared in the
      presence and absence of 100uM gentamicin (the recommended concentration for cell
      culture conditions). Spike-rate based EC50 values were generated using sigmoidal
      fit concentration response curves (CRCs). Exposure to 100uM gentamicin exhibited
      a muscimol EC50+/-S.E.M. of 80+/-6nM (n=10). The EC50 value obtained in the
      absence of gentamicin was 124+/-11nM (n=10). The 35% increase in potency suggests
      network sensitization to muscimol in the presence of gentamicin. Action potential
      (AP) waveform analyses of neurons exposed to gentamicin demonstrated a
      concentration-dependent decrease in AP amplitudes (extracellular recordings),
      possibly reflecting gentamicin effects on voltage-gated ion channels. These in
      vitro results reveal alteration of pharmacological responses by antibiotics that
      could have significant influence on the behavior and performance of animals.

PMID- 27864106
TI  - WITHDRAWN: Transurethral Resection of Prostate and Bleeding: A Prospective
      Randomized, Double-blind, Placebo-controlled Trial to See Efficacy of Short-term
      Use of Finasteride and Dutasteride on Operative Blood Loss and Prostatic
      Microvessel Density.
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- 27864105
TI  - Epigallocatechin-3-gallate prevents cardiac apoptosis by modulating the intrinsic
      apoptotic pathway in isoproterenol-induced myocardial infarction.
AB  - (-)Epigallocatechin-gallate (EGCG) is an emerging natural therapy. This study
      examined the cardioprotective effect of EGCG on isoproterenol-induced myocardial
      damage and apoptosis and EGCG's role in modulating the expression of apoptotic
      signaling proteins. Experimental myocardial infarction was induced in albino
      Westar rats by isoproterenol (ISO) administration (100mg/kg, s.c.) at an interval
      of 24h on the 6th and 7th day. EGCG (15mg/kg, i.p.) was administered seven days
      before ISO. EGCG pretreatment significantly showed an anti-lipidemic effect and
      protected the cell membrane integrity, as shown by the blocking of changes in
      serum levels of CK-MB, LDH, ALP, ALT and troponin T. EGCG also maintained the
      redox balance by preventing the inhibition of the activity of SOD and CAT while
      limiting lipid peroxidation. Pretreatment with EGCG inhibited the stimulation of
      the pro-inflammatory cytokine, TNF-alpha, in the serum. In animals treated with
      EGCG, tissue Bcl-2 expression exceeded the values observed after ISO treatment
      and down-regulated the expression of pro-apoptotic signaling proteins, including
      Bax, caspase-9 and 3. This is accompanied by the protection of genomic integrity
      by inhibiting DNA fragmentation coincident with the down-regulation of P53. In
      conclusion, EGCG protected against cardiac damage by decreasing apoptosis in
      myocardium tissue by 1) maintaining the balance of anti-apoptotic / pro-apoptotic
      signaling proteins in the mitochondrial pathway of cell death, 2) limiting
      oxidative stress while performing antioxidant and anti-inflammatory effects, and
      3) protecting DNA integrity, sustaining cardiac health. Therefore, EGCG is
      potentially beneficial as an early intervention in cardiac attack.

PMID- 27864107
TI  - Should Hypoechoic Lesions on Transrectal Ultrasound Be Sampled During Magnetic
      Resonance Imaging-targeted Prostate Biopsy?
AB  - OBJECTIVE: To determine whether supplemental biopsy of hypoechoic ultrasound
      lesions (HUL) incidentally found during magnetic resonance imaging (MRI)
      transrectal ultrasound (TRUS) fusion-targeted prostate biopsy results in improved
      prostate cancer (PCa) detection. METHODS: Patients underwent MRI-TRUS-targeted
      biopsy as part of an ongoing prospective trial from August 2007 to February 2015.
      For men with HUL, the biopsy pathology of HUL and MRI lesions was classified
      according to the updated 2014 International Society of Urological Pathology
      (ISUP) grading system. The detection of PCa by MRI-targeted biopsy with and
      without HUL biopsy was compared. RESULTS: Of 1260 men in the trial, 106 underwent
      biopsy of 119 HULs. PCa was diagnosed in 52 out of 106 men (49%) by biopsy of
      either MRI lesions or HUL. Biopsy of HUL in addition to MRI lesions resulted in 4
      additional diagnoses of high-grade (ISUP grades 3-5) PCa versus biopsy of MRI
      lesions alone (20 vs 16 men, P = .046). Three of these cases were upgraded from
      lower grade (ISUP grades 1-2) PCa on MRI-guided biopsy alone, and only 1 case (1%
      of cohort) was diagnosed that would have been missed by MRI-guided biopsy alone.
      Supplemental biopsy of HUL did not change the PCa risk category in 96% (102 out
      of 106) of men with HUL. CONCLUSION: Supplemental biopsy of HUL yields a small
      increase in the detection of higher grade PCa as compared with biopsy of MRI
      lesions alone. As upgrading is rare, routinely screening for HUL during MRI
      targeted biopsy remains controversial.

PMID- 27864108
TI  - Biopsy Perineural Invasion in Prostate Cancer Patients Who Are Candidates for
      Active Surveillance by Strict and Expanded Criteria.
AB  - OBJECTIVE: To evaluate the association of biopsy perineural invasion (PNI) with
      adverse pathologic findings on radical prostatectomy in patients who would have
      been candidates for active surveillance (AS). METHODS: Using a prospectively
      populated database of 3084 men who underwent open radical prostatectomy,
      candidates for AS by strict (Johns Hopkins) and expanded (University of Toronto)
      criteria were identified. The presence of adverse pathologic features at radical
      prostatectomy was compared between those men with and without biopsy PNI.
      RESULTS: Of 596 men who met strict criteria for AS, 16 (3%) had biopsy PNI. In
      the strict AS cohort, there were no differences in adverse pathologic features at
      radical prostatectomy between those with and without PNI. Of 1197 men who were
      candidates for AS by expanded criteria, 102 (9%) had biopsy PNI. Men with biopsy
      PNI in the expanded AS cohort were more likely to have extraprostatic extension
      (P < .001) and pathologic upgrading (P = .01) at prostatectomy. In addition,
      those with PNI had larger dominant nodules (P < .001), and cancer comprised a
      greater percentage of their prostate glands (P < .001). There was no difference
      in the proportion with a positive margin between the 2 groups (P = .77).
      CONCLUSION: Biopsy PNI was rare in patients who met strict criteria for AS. Among
      those men who met expanded criteria, PNI was associated with adverse pathologic
      findings upon prostatectomy. The presence of biopsy PNI may have a role in
      further risk stratifying patients who meet expanded criteria for AS.

PMID- 27864109
TI  - Selective cytotoxicity of microcystins LR, LW and LF in rat astrocytes.
AB  - Microcystins (MCs) comprise a group of cyanobacterial toxins with hepatotoxic,
      nephrotoxic and, possibly, neurotoxic activity in mammals. In order to understand
      the development of their neurotoxicity we investigated the toxic effects of MC
      variants, MC-LR, MC-LW and MC-LF, in astrocytes that play a central role in
      maintaining brain homeostasis. 24h exposure of cultured rat cortical astrocytes
      to MCs revealed dose-dependent toxicity of MC-LF and MC-LW, but not of MC-LR,
      observed by significant reduction in cell number, declined viability monitored by
      MTT test and an increased percentage of apoptotic cells, confirmed by Annexin-V
      labelling. The cultured astrocytes expressed organic anion-transporting
      polypeptides (Oatp) Oatp1a4, Oatp1c1 and Oatp1a5, but not Oatp1b2. Intracellular
      localisation of MC-LF and MC-LW, proven by anti-Adda primary antibody,
      demonstrated transport of tested MCs into cultured astrocytes. Acute MC-LW and MC
      LF intoxication induced cytoskeletal disruption as seen by the degradation of
      glial fibrillary acid protein (GFAP), actin and the tubulin network. In this in
      vitro study, MC-LF and MC-LW, but not MC-LR, are shown to cause the dysfunction
      of astrocytic homeostatic capabilities, already at low concentrations, suggesting
      that astrocyte atrophy, with loss of function, could be expected in the brain
      response to the toxic insult.

PMID- 27864110
TI  - Antinociceptive activity and mechanism of action of hydroalcoholic extract and
      dichloromethane fraction of Amphilophium crucigerum seeds in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant generally known as monkey's
      comb (Amphilophium crucigerum) has been popularly described for the treatment of
      neuropathic and inflammatory pain, specially seeds preparations. AIM OF THE
      STUDY: The goal of the present study was to evaluate the antinociceptive effect
      of the crude extract (Crd) and dichloromethane fraction (Dcm) of A. crucigerum
      seeds, and investigate the involvement of transient receptor potential vanilloid
      1 (TRPV1) receptor in this effect. MATERIALS AND METHODS: Male Swiss mice were
      used in this study. The effects of Crd and Dcm was tested on capsaicin-induced
      Ca2+ influx or the specific binding of [3H]-resiniferatoxin. Moreover, after
      treatment with Crd or Dcm, animals were exposed to acute pain (hot water tail
      flick and capsaicin intraplantar test) or chronic pain models (injection of
      complete Freund's adjuvant or partial ligation of the sciatic nerve). Acute
      adverse effects were also noted: locomotor activity, corporal temperature,
      hepatic or renal damage, gastrointestinal transit alteration, and ulcerogenic
      activity. RESULTS: The oral administration of Crd or Dcm resulted in an
      antinociceptive effect in the hot water tail-flick (48 degrees C) and capsaicin
      intraplantar tests. Furthermore, these preparations exhibited antinociceptive and
      anti-inflammatory effects in a chronic inflammatory pain model, and
      antinociceptive effects in a neuropathic pain model. Moreover, Crd and Dcm
      reduced capsaicin-induced Ca2+ influx and diminished the [3H]-resiniferatoxin
      specific binding to spinal cord membranes. Acute adverse events were not found
      with Crd or Dcm administration. CONCLUSION: In conclusion, our results support
      the analgesic effect of A. crucigerum and suggest the presence of compounds that
      may act as TRPV1 antagonists.

PMID- 27864111
TI  - Secondary metabolites from Tetracera potatoria stem bark with anti-mycobacterial
      activity.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tetracera potatoria Afzel. Exg. Don
      (Dilleniaceae) is a medicinal plant used traditionally in Africa for the
      treatment of tuberculosis related ailments and respiratory infections. The
      antibacterial activity of the medium polar extracts of T. potatoria leaves and
      stem bark was recently reported against Mycobacterium smegmatis (MIC 25ug/mL) and
      M. aurum (65ug/mL), two fast-growing Mycobacterium strains used as model micro
      organisms for the more pathogenic strain Mycobacterium tuberculosis (Fomogne
      Fodjo et al., 2014). The aim of this study was consequently to isolate the
      compounds possibly contributing to this activity, and which may therefore be
      promising precursors to be used for the development of novel anti-TB drugs.
      MATERIALS AND METHODS: T. potatoria medium polar extract [MeOH/DCM (1:1, v/v)]
      was fractionated sequentially with petroleum ether to which EtOAC and MeOH were
      gradually added to increase the polarity. The examination of T. potatoria extract
      and its fractions was guided by bioassays for anti-mycobacterial activity against
      M. smegmatis (ATCC 23246) and M. aurum (NCTC 10437) using the minimum inhibitory
      concentration (MIC) method. All the isolated compounds were structurally
      elucidated using spectroscopic techniques and evaluated for their anti
      mycobacterial activity. RESULTS: Two novel secondary metabolites (1, 2) named
      tetraceranoate and N-hydroxy imidate-tetracerane, together with five known
      compounds [beta-stigmasterol (3), stigmast-5-en-3beta-yl acetate (4), betulinic
      acid (5), betulin (6) and lupeol (7)] were isolated and identified.
      Tetraceranoate exhibited the best activity against M. smegmatis with a minimum
      inhibitory concentration (MIC) of 7.8ug/mL, while beta-stigmasterol, betulinic
      acid and betulin showed appreciable anti-mycobacterial activity against both
      strains (MIC 15ug/mL). CONCLUSION: Seven compounds were isolated from the medium
      polar extract [MeOH/DCM (1:1, v/v)] of T. potatoria stem bark. Only
      tetraceranoate one of the isolated compounds showed antibacterial activity
      against M. smegmatis having efficacy as high as rifampicin (one of a three drug
      regimen recommended in the initial phase short-course anti-tuberculosis therapy).
      Thus, tetraceranoate might be an interesting target for systematic testing of
      anti-TB treatment and management. This research supports the use of T. potatoria
      in African traditional medicine for the treatment of tuberculosis related
      symptoms.

PMID- 27864112
TI  - Polar extracts from the berry-like fruits of Hypericum androsaemum L. as a
      promising ingredient in skin care formulations.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The top flowering aerial parts of the Hypericum
      species are traditionally used to prepare ointments to heal cuts and burns.
      Sometimes even the fruits are used for these purposes. Hypericum androsaemum L.,
      commonly known as tutsan or shrubby St. John's Wort, is a Mediterranean medicinal
      plant which has been traditionally used to prepare an ointment for treating cuts
      and wounds. AIM OF THE STUDY: To evaluate the extracts obtained from H.
      androsaemum red berries as functional ingredients for skin care formulations.
      MATERIALS AND METHODS: The methanolic extract was obtained by Soxhlet extraction
      while the aqueous extract was prepared by decoction; their composition was
      determined by HPLC analysis. Their biological activities were measured in terms
      of proliferation and migration of human fibroblasts, inhibition of collagenase
      activity, and immunomodulatory effects on human peripheral blood mononuclear
      cells (PBMCs). In addition, we evaluated their photostability by UV spectroscopy
      and their protective effects against APPH-induced hemolysis in red blood cells
      (RBC). RESULTS: The polar extracts contained significant amounts of shikimic
      (108,143.7-115,901.3mg/kg) and chlorogenic acids (45,781.1-57,002.7mg/kg). The
      main components of these extracts made an important contribution to a significant
      increase in human fibroblast migration. Both extracts were also active as
      collagenase inhibitors, with the aqueous one showing a greater inhibitory
      capacity (IC50 value of 88.1ug/mL), similar to that of chlorogenic acid. The
      kinetic parameters determined for the enzymatic reaction revealed for both
      aqueous extract and chlorogenic acid an uncompetitive mechanism of inhibition.
      The methanolic extract showed important effects on PBMCs by modulating IL-6. Both
      extracts proved to be photostable in the UVA/B range and protected RBC against
      peroxidation at low concentrations. CONCLUSIONS: H. androsaemum red berries were
      proven to contain phytochemicals that improve skin regeneration, hence
      potentially employable in skin care formulations.

PMID- 27864113
TI  - Chenopodium album Linn. leaves prevent ethylene glycol-induced urolithiasis in
      rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Chenopodium album Linn. are
      traditionally used for correction of kidney diseases and urinary stones. The
      present work investigated the effect of methanolic and aqueous extracts of leaves
      of Chenopodium album on experimentally-induced urolithiasis in rats to
      substantiate its traditional use as antilithiatic agent. MATERIALS AND METHODS:
      The leaf extract was standardized by HPLC. Urolithiasis was induced in rats by
      administration of 0.75% v/v of ethylene glycol (EG) in distilled water and in
      addition, vehicle or methanol (CAME) or aqueous (CAAE) extract of the leaves of
      Chenopodium album each in the dose 100, 200 and 400mg/kg or Cystone (750mg/kg)
      were administered daily orally for 28 days. Urolithiasis was assessed by
      estimating the calcium, phosphorus, urea, uric acid, and creatinine in both urine
      and plasma. The volume, pH and oxalate levels were also estimated in urine. The
      renal oxalate content was estimated in kidney while calcium oxalate deposits were
      observed histologically. RESULTS: The treatment with CAME or CAAE for 28 days
      significantly attenuated the EG-induced elevations in the urine and plasma levels
      of calcium, phosphorus, urea, uric acid and creatinine along with decrease in
      urine volume, pH and oxalates. The treatments also decreased renal tissue oxalate
      and deposition of oxalate crystals in kidney due to EG treatment. The effects of
      CAME and CAAE were comparable to standard antilithiatic agent, cystone. The
      findings indicate the preventive effect of CAME and CAAE which can be due to
      inhibitory effect on crystallization and stone dissolution. The effect was
      attributed to the presence of phytochemicals like flavonoids and saponins.
      CONCLUSION: In conclusion, Chenopodium album leaves exhibited antilithiatic
      effect and validates its ethnomedicinal use in urinary disorders and kidney
      stones.

PMID- 27864114
TI  - Lipopolysaccharide promotes tumorigenicity of hepatic progenitor cells by
      promoting proliferation and blocking normal differentiation.
AB  - Hepatic progenitor cells (HPCs) are bipotential stem cells that can differentiate
      into mature hepatocytes or biliary epithelial cells (BECs). They are thought to
      be involved in repair of liver injury and the incidence of hepatic carcinoma.
      Their physiology is closely associated with the microenvironment where they
      reside. Lipopolysaccharide (LPS), an important component of the hepatic
      pathological microenvironment, is stored in the liver and affects many types of
      cells in various hepatosis. HPCs may also be influenced by LPS. In this paper,
      mouse ED13.5 E-cadherin+ foetal liver cells were isolated as mouse hepatic
      progenitor cells (mHPCs). Proliferation of mHPCs was promoted under LPS
      conditions both in vivo and in vitro. Moreover, LPS enhanced colony formation
      ability of mHPCs, and blocked them differentiation into mature hepatocytes and
      formation of a bile duct-liked structure. More importantly, long-term treatment
      with LPS promoted tumorigenesis of mHPCs in nude mice. Thus, we conclude that LPS
      may promote aberrant proliferation of mHPCs and restrict their normal
      differentiation. Long-term exposure of mHPCs to LPS increased the risk of tumour
      formation. These data provide insight into the links between LPS, HPCs fate, and
      tumorigenesis, and present novel insight into the relationship between HPCs and
      their microenvironment.

PMID- 27864115
TI  - Synergistic antitumor activity of regorafenib and lapatinib in preclinical models
      of human colorectal cancer.
AB  - Regorafenib significantly prolongs overall survival in patients with metastatic
      colorectal cancer (mCRC), but the overall clinical efficacy of regorafenib
      remains quite limited. Combination chemotherapy is a potentially promising
      approach to enhance anticancer activity, overcome drug resistance, and improve
      disease-free and overall survival. The current study investigates the antitumor
      activity of regorafenib in combination with lapatinib in preclinical models of
      human CRC. Our results show improved antitumor efficacy when regorafenib is
      combined with lapatinib both in vitro and in vivo. Furthermore, pharmacokinetic
      analyses revealed that regorafenib and lapatinib do not influence on each plasma
      concentration. The finding that regorafenib in combination with lapatinib have
      synergistic activity warrants further clinical investigation of this beneficial
      combination as a potential treatment strategy for CRC patients.

PMID- 27864116
TI  - Solid pseudopapillary tumor: a new tumor entity in the testis? Reply.

PMID- 27864117
TI  - Microcystic, elongated, and fragmented pattern invasion is mainly associated with
      isolated tumor cell pattern metastases in International Federation of Gynecology
      and Obstetrics grade I endometrioid endometrial cancer.
AB  - Although many studies have evaluated the impact of mismatch repair protein loss
      of expression (MMR LOE) or microcystic, elongated, and fragmented (MELF) pattern
      of myometrial invasion as individual factors in endometrial cancer, we analyzed
      the combined impact of both. We reviewed every case of International Federation
      of Gynecology and Obstetrics (FIGO) grade 1 endometrioid endometrial cancers
      (EECs) from our institution, between 2011 and 2015, that had a sentinel lymph
      node biopsy and/or a lymphadenectomy, and examined the following data: age,
      myometrial infiltration, MELF infiltration, lymphovascular space invasion, and
      lymph node status. These cases were then grouped according to the absence of
      lymph node metastases, the presence of isolated tumor cell (ITC) lymph node
      metastases, or the presence of non-ITC metastases. Among the 127 cases that were
      in our study, 105 patients did not have nodal metastases, whereas 22 patients
      showed metastases, of which 11 were ITC. MMR LOE was only significantly
      associated with a higher odds ratio (OR) of metastases (OR, 7.44; P < .001). MELF
      was only associated with a higher OR of ITC-pattern metastases (OR, 32.3; P <
      .001). This study distinguished the effects of MELF and MMR LOE on the risk of
      metastases in FIGO grade 1 EEC. Further research on the clinical impact of MELF
      and ITC-pattern metastases is warranted to better guide clinicians on the
      management of patients with FIGO grade 1 EEC harboring such characteristics,
      which are still considered low-risk cancer.

PMID- 27864118
TI  - Azzopardi phenomenon reported in metal-on-metal arthroplasties is in fact iron
      encrustation of blood vessels.

PMID- 27864119
TI  - Role of miR-139 as a surrogate marker for tumor aggression in breast cancer.
AB  - MicroRNAs are non-protein coding molecules that play a key role in oncogenesis,
      tumor progression, and metastasis in many types of malignancies including breast
      cancer. In the current study, we studied the expression of microRNA-139-5p (miR
      139) in invasive ductal carcinoma (IDC) of the breast and correlated its
      expression with tumor grade, molecular subtype, hormonal status, human epidermal
      growth factor receptor 2 status, proliferation index, tumor size, lymph node
      status, patient's age, and overall survival in 74 IDC cases. In addition, we
      compared and correlated miR-139 expression in 18 paired serum and tissue samples
      from patients with IDC to assess its value as a serum marker. Our data showed
      that miR-139 was down-regulated in all tumor tissue samples compared with
      control. More pronounced down-regulation was seen in tumors that were higher
      grade, estrogen receptor negative, progesterone receptor negative, more
      proliferative, or larger in size (P < .05). Although not statistically
      significant, lower miR-139 level was frequently associated with human epidermal
      growth factor receptor 2 overexpression. In addition, significantly lower miR-139
      tissue level was seen in patients who were deceased (P = .027), although older
      age (>50 years) and positive local nodal disease did not adversely affect miR-139
      expression. In contrast, serum miR-139 profile of the patients appeared similar
      to that of normal control. In conclusion, our study demonstrated that down
      regulation of miR-139 was associated with aggressive tumor behavior and disease
      progression in breast cancer. miR-139 may serve as a risk assessment biomarker in
      tailoring treatment options.

PMID- 27864120
TI  - Epidermal growth factor receptor as an adverse survival predictor in squamous
      cell carcinoma of the penis.
AB  - Penile carcinoma (PC) is more frequent in underdeveloped countries, generally is
      diagnosed at an advanced stage when therapeutic options are restricted, and thus
      is associated with high morbidity/mortality rates. Recent studies have
      demonstrated clinical benefits with epidermal growth factor receptor (EGFR)
      targeted therapy in patients with PC, although there is no test that provides
      accurate patient selection. The aim of the present study was to evaluate the
      prognostic value of EGFR gene and protein status in tumor samples from patients
      with primary penile squamous cell carcinoma. We assessed the expression of wild
      type and 2 mutant EGFR isoforms (delA746-E750 and mL858R) by immunohistochemistry
      in 139 samples, of which 49 were also evaluated for EGFR copy number by
      fluorescence in situ hybridization (FISH). Positive immunohistochemical staining
      of wild-type and mutant EGFR was evidenced by complete and strong membranous
      staining. For FISH analysis, cases were considered unaltered, polysomic, or
      amplified, as determined by signals of the EGFR gene and chromosome 7. An
      independent cohort of 107 PC samples was evaluated for mutations in EGFR, KRAS,
      and BRAF. Protein overexpression was noted in nearly half of the cases and was
      associated with cancer recurrence (P=.004) and perineural invasion (P=.005).
      Expression of the 2 mutated EGFR isoforms was not observed. The FISH status was
      not associated with protein expression. Altered FISH (polysomy and gene
      amplification) was an independent risk factor for dying of cancer. Only 1 patient
      of 107 presented KRAS mutations, and no mutations of EGFR or BRAF were observed.

PMID- 27864121
TI  - Gene amplification of CCNE1, CCND1, and CDK6 in gastric cancers detected by
      multiplex ligation-dependent probe amplification and fluorescence in situ
      hybridization.
AB  - New and effective treatments for advanced gastric cancer are urgently needed.
      Cyclins E and D1 form a complex with cyclin-dependent kinase 2, 4, or 6 to
      regulate G1-S transition. The G1-S regulatory genes encoding cyclin E (CCNE1),
      cyclin D1 (CCND1), and CDK6 (CDK6) are frequently amplified in gastric cancer and
      may therefore influence molecularly targeted therapies against ERBB2 or EGFR when
      coamplified. A total of 179 formalin-fixed and paraffin-embedded gastric cancer
      specimens were examined for these gene amplifications by multiplex ligation
      dependent probe amplification and fluorescence in situ hybridization.
      Amplification of at least 1 G1-S regulatory gene was found in 35 tumors (CCNE1
      amplification, 15% of samples; CCND1, 6%; CDK6, 1%). In 13 of the 35 tumors, dual
      color fluorescence in situ hybridization identified coamplification of the G1-S
      regulatory genes with ERBB2, EGFR, and/or KRAS in single cancer nuclei. The
      observation that cells with G1-S regulatory gene amplification contained clonal
      subpopulations with coamplification of ERBB2, EGFR, or KRAS in 5 early and 3
      advanced cancers suggests that amplification of the G1-S regulatory genes
      represents an early event, which precedes ERBB2, EGFR, or KRAS amplification.
      Amplified CCNE1, CCND1, and CDK6 in advanced gastric cancer may be potentially
      useful as direct targets for molecular therapy or for combination therapy with
      ERBB2 or EGFR inhibitors. Multiplex ligation-dependent probe amplification could
      be a useful tool for identification of patients who would benefit from such
      therapies.

PMID- 27864122
TI  - Sclerosing TFEB-rearrangement renal cell carcinoma: a recurring histologic
      pattern.
AB  - Renal cell carcinoma with TFEB rearrangement (t[6;11][p21;q13]) was initially
      recognized to be composed of dual populations of large cells with clear cytoplasm
      and small cells forming rosettes around hyaline material. With increasing
      awareness, however, the spectrum of described morphology has been found to be
      more heterogeneous. We report a 54-year-old woman who underwent partial
      nephrectomy for a 2.4-cm renal mass, composed of fibrosis, hyalinization,
      calcification, and ossification and a smaller component of epithelioid cells.
      Immunohistochemical staining revealed diffuse positivity for cytokeratin AE1/AE3
      and PAX8, patchy labeling for melan-A, human melanosome, and cathepsin K, and
      negative caldesmon, smooth muscle actin, TFE3 protein, carbonic anhydrase IX,
      CD10, cytokeratin 7, epithelial membrane antigen, and inhibin. Fluorescence in
      situ hybridization confirmed rearrangement of TFEB and not TFE3. Together with
      one recent case in another report, our findings suggest that extensive sclerosis
      and ossification may be a less common recurring histology of TFEB-rearrangement
      renal cell carcinoma.

PMID- 27864123
TI  - PTEN/PI3K/AKT protein expression is related to clinicopathological features and
      prognosis in breast cancer with axillary lymph node metastases.
AB  - We explored the relations between PTEN/PI3K/AKT expression and
      clinicopathological characteristics and prognosis in breast cancer patients with
      and without axillary lymph node metastasis (LNM). Tissues and follow-up data from
      142 patients with (LNM group) and 154 without (non-LNM group) metastases were
      collected. Expression of PTEN/PI3K/AKT was detected using immunohistochemistry
      staining. With axillary LNM, the positive rate of PTEN was reduced, whereas that
      of PI3K and AKT was increased. Expression of AKT was negatively correlated with
      PTEN expression but positively correlated with PI3K expression. Apparent
      correlations were detected between AKT and axillary LNM with a tumor size of 2 cm
      or less; between PTEN, PI3K, and AKT and axillary LNM in stage T1 or T2 breast
      cancer and invasive carcinoma of a nonspecial type; and between PTEN and AKT and
      axillary LNM of histologic grade I or II tumors and non-triple-negative breast
      cancer (all P<.05). In the LNM group, the 5-year survival rate of patients with
      PTEN-positive tumors was higher than that of patients with PTEN-negative lesions;
      whereas in the non-LNM group, the 5-year survival rate of patients with AKT
      positive tumors was lower than that of patients with AKT-negative lesions (both
      P<.05). Cox regression analysis showed that PTEN expression was an independent
      prognostic factor for patients with LNM; AKT expression, tumor diameter,
      pathologic grade, and pathologic type were independent prognostic factors for
      patients without LNM. In conclusion, TEN/PI3K/AKT proteins are related to the
      clinicopathological features and prognosis of breast cancer with axillary LNM.

PMID- 27864124
TI  - CD133 expression in well-differentiated pancreatic neuroendocrine tumors: a
      potential predictor of progressive clinical courses.
AB  - The present study aimed to elucidate whether the stemness molecule, CD133, is
      expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World
      Health Organization grades 1 and 2) and establish its clinical relevance using 2
      separate cohorts. In the first series (n = 178) in which tissue microarrays were
      available, immunohistochemistry revealed that CD133 was expressed in 14 cases
      (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent
      lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the
      second cohort (n = 56), the expression of CD133 and CK19 was examined in whole
      tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases,
      respectively. CD133 expression correlated with higher pT scores (P < .01), the
      presence of microscopic venous infiltration (P = .03), and shorter disease-free
      periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients
      with CD133+ PanNET continued to have shorter disease-free periods than did those
      with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although
      CK19+ cases had shorter disease-free periods than did CK19- cases in the whole
      cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and
      2 cases. CD133 expression also appeared to be an independent predictive factor
      for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype
      was identical between primary and metastatic foci in 17 of 18 cases from which
      tissues of metastatic deposits were available. In conclusion, the combination of
      CD133 phenotyping and World Health Organization grading may assist in stratifying
      patients in terms of the risk of progressive clinical courses.

PMID- 27864125
TI  - Solid pseudopapillary tumor: a new tumor entity in the testis?

PMID- 27864126
TI  - The Use of Life-Sustaining Procedures in the Last Month of Life Is Associated
      With More Depressive Symptoms in Surviving Spouses.
AB  - CONTEXT: Family caregivers of individuals with serious illness who undergo
      intensive life-sustaining medical procedures at the end of life may be at risk of
      negative consequences including depression. OBJECTIVES: The objective of this
      study was to determine the association between patients' use of life-sustaining
      procedures at the end of life and depressive symptoms in their surviving spouses.
      METHODS: We used data from the Health and Retirement Study, a longitudinal survey
      of U.S. residents, linked to Medicare claims data. We included married Medicare
      beneficiaries aged 65 years and older who died between 2000 and 2011 (n = 1258)
      and their surviving spouses. The use of life-sustaining procedures (i.e.,
      intubation/mechanical ventilation, tracheostomy, gastrostomy tube insertion,
      enteral/parenteral nutrition, and cardiopulmonary resuscitation) in the last
      month of life was measured via claims data. Using propensity score matching, we
      compared change in depressive symptoms of surviving spouses. RESULTS: Eighteen
      percent of decedents underwent one or more life-sustaining procedures in the last
      month of life. Those whose spouses underwent life-sustaining procedures had a
      0.32-point increase in depressive symptoms after death (scale range = 0-8) and a
      greater likelihood of clinically significant depression (odds ratio = 1.51)
      compared with a matched sample of spouses of those who did not have procedures (P
      < 0.05). CONCLUSION: Surviving spouses of those who undergo intensive life
      sustaining procedures at the end of life experience a greater magnitude of
      increase in depressive symptoms than those whose spouses do not undergo such
      procedures. Further study of the circumstances and decision making surrounding
      these procedures is needed to understand their relationship with survivors'
      negative mental health consequences and how best to provide appropriate support.

PMID- 27864129
TI  - Pretreatment of cashew apple bagasse using protic ionic liquids: Enhanced
      enzymatic hydrolysis.
AB  - To enhance the enzymatic digestibility of cashew apple bagasse (CAB) feedstock in
      order to produce sugar fermentation-derived bioproducts, the CAB was subjected to
      three different pretreatments with the ionic liquid 2-hydroxyl-ethylammonium
      acetate (2-HEAA) and characterized by FTIR, NMR and chemical methods. All
      conditions were able to delignify CAB, however the best lignin removal (95.8%)
      was achieved through the method performed with 8.7% w/w of CAB/2-HEAA ratio at
      130 degrees C for 24h. Although the cellulose crystallinity has been increased in
      CAB treated with the ionic liquid, but this fact did not influence its
      digestibility. Nevertheless, the pretreatment with 2-HEAA enhanced significantly
      the cellulose digestibility, increasing the glucose yield from 48 to
      747.72mgglucose/gCAB. Furthermore, 2-HEAA pretreatment was efficient even with
      reused ionic liquid, obtaining high glucose concentration.

PMID- 27864127
TI  - No Difference Between Latiglutenase and Placebo in Reducing Villous Atrophy or
      Improving Symptoms in Patients With Symptomatic Celiac Disease.
AB  - BACKGROUND & AIMS: Gluten ingestion leads to symptoms and small intestinal
      mucosal injury in patients with celiac disease. The only option is the strict
      lifelong exclusion of dietary gluten, which is difficult to accomplish. Many
      patients following a gluten-free diet continue to have symptoms and have small
      intestinal mucosal injury. Nondietary therapies are needed. We performed a phase
      2 study of the ability of latiglutenase, an orally administered mixture of 2
      recombinant gluten-targeting proteases, to reduce mucosal morphometric measures
      in biopsy specimens from patients with celiac disease. METHODS: We performed a
      double-blind, placebo-controlled, dose-ranging study to assess the efficacy and
      safety of latiglutenase in 494 patients with celiac disease (with moderate or
      severe symptoms) in North America and Europe, from August 2013 until December
      2014. Participants reported following a gluten-free diet for at least 1 year
      before the study began. Patients with documented moderate or severe symptoms and
      villous atrophy (villous height:crypt depth ratio of <=2.0) were assigned
      randomly to groups given placebo or 100, 300, 450, 600, or 900 mg latiglutenase
      daily for 12 or 24 weeks. Subjects completed the Celiac Disease Symptom Diary
      each day for 28 days and underwent an upper gastrointestinal endoscopy with
      duodenal biopsy of the distal duodenum at baseline and at weeks 12 and 24. The
      primary end point was a change in the villous height:crypt depth ratio. Secondary
      end points included numbers of intraepithelial lymphocytes, serology test results
      (for levels of antibodies against tissue transglutaminase-2 and deamidated
      gliadin peptide), symptom frequencies, and safety. RESULTS: In a modified intent
      to-treat population, there were no differences between latiglutenase and placebo
      groups in change from baseline in villous height:crypt depth ratio, numbers of
      intraepithelial lymphocytes, or serologic markers of celiac disease. All groups
      had significant improvements in histologic and symptom scores. CONCLUSIONS: In a
      phase 2 study of patients with symptomatic celiac disease and histologic evidence
      of significant duodenal mucosal injury, latiglutenase did not improve histologic
      and symptom scores when compared with placebo. There were no significant
      differences in change from baseline between groups. ClinicalTrials.gov no:
      NCT01917630.

PMID- 27864128
TI  - Prostaglandin E2 Activates YAP and a Positive-Signaling Loop to Promote Colon
      Regeneration After Colitis but Also Carcinogenesis in Mice.
AB  - BACKGROUND & AIMS: Prostaglandin E2 (PGE2) is mediator of inflammation that
      regulates tissue regeneration, but its continual activation has been associated
      with carcinogenesis. Little is known about factors in the PGE2 signaling pathway
      that contribute to tumor formation. We investigated whether yes-associated
      protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway,
      mediates PGE2 function. METHODS: DLD-1 and SW480 colon cancer cell lines were
      transfected with vectors expressing transgenes or small hairpin RNAs and
      incubated with recombinant PGE2, with or without pharmacologic inhibitors of
      signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative
      reverse-transcription polymerase chain reaction, transcriptional reporter, and
      proliferation assays. Dextran sodium sulfate (DSS) was given to induce colitis in
      C57/BL6 (control) mice, as well as in mice with disruption of the
      hydroxyprostaglandin dehydrogenase 15 gene (15-PGDH-knockout mice), Yap1 gene
      (YAP-knockout mice), and double-knockout mice. Some mice also were given
      indomethacin to block PGE2 synthesis. 15-PGDH knockout mice were crossed with
      mice with intestine-specific disruption of the salvador family WW domain
      containing 1 gene (Sav1), which encodes an activator of Hippo signaling. We
      performed immunohistochemical analyses of colon biopsy samples from 26 patients
      with colitis-associated cancer and 51 age-and sex-matched patients with
      colorectal cancer (without colitis). RESULTS: Incubation of colon cancer cell
      lines with PGE2 led to phosphorylation of cyclic adenosine monophosphate
      responsive element binding protein 1 and increased levels of YAP1 messenger RNA,
      protein, and YAP1 transcriptional activity. This led to increased transcription
      of the prostaglandin-endoperoxide synthase 2 gene (PTGS2 or cyclooxygenase 2) and
      prostaglandin E-receptor 4 gene (PTGER4 or EP4). Incubation with PGE2 promoted
      proliferation of colon cancer cell lines, but not cells with knockdown of YAP1.
      Control mice developed colitis after administration of DSS, but injection of PGE2
      led to colon regeneration in these mice. However, YAP-knockout mice did not
      regenerate colon tissues and died soon after administration of DSS. 15-PGDH
      knockout mice regenerated colon tissues more rapidly than control mice after
      withdrawal of DSS, and had faster recovery of body weight, colon length, and
      colitis histology scores. These effects were reversed by injection of
      indomethacin. SAV1-knockout or 15-PGDH-knockout mice did not develop spontaneous
      tumors after colitis induction, but SAV1/15-PGDH double-knockout mice developed
      polyps that eventually progressed to carcinoma in situ. Administration of
      indomethacin to these mice prevented spontaneous tumor formation. Levels of PGE2
      correlated with those of YAP levels in human sporadic colorectal tumors and
      colitis-associated tumors. CONCLUSIONS: PGE2 signaling increases the expression
      and transcriptional activities of YAP1, leading to increased expression of
      cyclooxygenase 2 and EP4 to activate a positive signaling loop. This pathway
      promotes proliferation of colon cancer cell lines and colon tissue regeneration
      in mice with colitis. Constitutive activation of this pathway led to formation of
      polyps and colon tumors in mice.

PMID- 27864130
TI  - Role of macrophyte and effect of supplementary aeration in up-flow constructed
      wetland-microbial fuel cell for simultaneous wastewater treatment and energy
      recovery.
AB  - This study investigates the role of plant (Elodea nuttallii) and effect of
      supplementary aeration on wastewater treatment and bioelectricity generation in
      an up-flow constructed wetland-microbial fuel cell (UFCW-MFC). Aeration rates
      were varied from 1900 to 0mL/min and a control reactor was operated without
      supplementary aeration. 600mL/min was the optimum aeration flow rate to achieve
      highest energy recovery as the oxygen was sufficient to use as terminal electron
      acceptor for electrical current generation. The maximum voltage output, power
      density, normalized energy recovery and Coulombic efficiency were 545.77+/-25mV,
      184.75+/-7.50mW/m3, 204.49W/kg COD, 1.29W/m3 and 10.28%, respectively. The
      variation of aeration flow rates influenced the NO3- and NH4+ removal differently
      as nitrification and denitrification involved conflicting requirement. In terms
      of wastewater treatment performance, at 60mL/min aeration rate, UFCW-MFC achieved
      50 and 81% of NO3- and NH4+ removal, respectively. E. nuttallii enhanced
      nitrification by 17% and significantly contributed to bioelectricity generation.

PMID- 27864131
TI  - Combinations of fungal and milling pretreatments for enhancing rice straw biogas
      production during solid-state anaerobic digestion.
AB  - Rice straw was pretreated by different combinations of physical (milling) and
      biological (incubation with Pleurotus ostreatus fungus) treatment to improve its
      biodegradability and biogas production during solid-state anaerobic digestion (SS
      AD). Effects of milling (?2mm) and incubation time (10, 20 and 30d), on lignin,
      cellulose, and hemicellulose degradation during fungal pretreatment and methane
      yield during digestion were assessed by comparison with untreated rice straw.
      Both incubation time and milling had significant impacts on both lignin removal
      during fungal pre-treatment and methane yield during digestion. A combination of
      fungal pretreatment at 30days followed by milling prior to anaerobic digestion
      resulted in 30.4% lignin removal, the highest selectivity value (the ratio
      between relative lignin removal and relative cellulose removal) of 4.22, and the
      highest methane yield of 258L/kgVS. This was equivalent to a 165% increase in
      methane yield from SS-AD compared to untreated rice straw.

PMID- 27864133
TI  - Pilot scale dilute acid pretreatment of rice straw and fermentable sugar recovery
      at high solid loadings.
AB  - The aim of this work was to study the dilute acid pretreatment of rice straw (RS)
      and fermentable sugar recovery at high solid loadings at pilot scale. A series of
      pretreatment experiments were performed on RS resulting in >25wt% solids followed
      by enzymatic hydrolysis without solid-liquid separation at 20 and 25wt% using
      10FPU/g of the pretreated residue. The overall sugar recovery including the
      sugars released in pretreatment and enzymatic hydrolysis was calculated along
      with a mass balance. Accordingly, the optimized conditions, i.e. 0.35wt% acid,
      162 degrees C and 10min were identified. The final glucose and xylose
      concentrations obtained were 83.3 and 31.9g/L respectively resulting in total
      concentration of 115.2g/L, with a potential to produce >50g/L of ethanol. This is
      the first report on pilot scale study on acid pretreatment of RS in a screw
      feeder horizontal reactor followed by enzymatic hydrolysis at high solid
      loadings.

PMID- 27864132
TI  - Effect of nickel on the flocculability, settleability, and dewaterability of
      activated sludge.
AB  - Short-term and long-term effects of nickel (Ni) (0.1-10mg/L) on the
      physicochemical properties of activated sludge, including the flocculability,
      settleability, and dewaterability, were investigated. It was found that these
      properties were unaffected after short-term exposure (1day) to Ni(II) even at the
      level of 10mg/L. After long-term exposure (60days) to 1 and 10mg/L of Ni(II),
      however, the sludge flocculability has seriously deteriorated, while the
      settleability, and dewaterability became gradually better than the control. The
      mechanism studies revealed that long-term exposure to Ni(II) resulted in the
      decrease of protein content in extracellular polymeric substances (EPS) and the
      damage to EPS structures. Although Ni(II) did not bring any adverse effect on the
      cell membrane, the relative hydrophobicity of activated sludge was significantly
      decreased. The negative effects on the flocculability and phosphorus removal
      performance of activated sludge could be completely eliminated by adding the
      chelator such as EDTA and citrate.

PMID- 27864135
TI  - Comparison of autohydrolysis and ionic liquid 1-butyl-3-methylimidazolium acetate
      pretreatment to enhance enzymatic hydrolysis of sugarcane bagasse.
AB  - The aim of this work was to evaluate the efficiency of an ionic liquid (IL) 1
      butyl-3-methylimidazolium acetate ([C4mim][OAc]) pretreatment (110 degrees C for
      30min) in comparison to high severity autohydrolysis pretreatment in terms of
      delignification, cellulose crystallinity and enzymatic digestibility. The
      increase in severity of autohydrolysis pretreatment had positive effect on glucan
      digestibility, but was limited by the crystallinity of cellulose. [C4mim][OAc]
      pretreated sugarcane bagasse exhibited a substantial decrease in lignin content,
      reduced cellulose crystallinity, and enhanced glucan and xylan digestibility.
      Glucan and xylan digestibility was determined as 97.4% and 98.6% from
      [C4mim][OAc] pretreated bagasse, and 62.1% and 57.5% from the bagasse
      autohydrolyzed at 205 degrees C for 6min, respectively. The results indicated the
      improved digestibility and hydrolysis rates after [C4mim][OAc] pretreatment when
      compared against a comparable autohydrolyzed biomass.

PMID- 27864134
TI  - Biochemical methane potential of oil-extracted microalgae and glycerol in co
      digestion with chicken litter.
AB  - The objective of this work was to evaluate the technical feasibility of using
      both oil-extracted microalgae (M) and glycerol (G) in co-digestion with chicken
      litter (CL), thereby improving biochemical methane potential (BMP). Different
      feedstock ratios of M (0-30%), G (0-3%) and CL (67-100%) were investigated to
      determine the best co-digestion condition under mesophilic conditions. According
      to the modified Gompertz model, the best BMP (131.1mLCH4gVSfed-1) was obtained
      with the triple co-digestion (M:G:CL) in a proportion of 30:3:67. This yielded a
      methane production rate (MUm) of 3.3mLCH4gVSfed-1d-1 and a lag time (lambda) of
      17.4d. This treatment reduced chemical oxygen demand (COD) by 91.02% and
      increased the methane yield 15.8% with respect to the CL control.

PMID- 27864136
TI  - The underlying mechanisms of genetic innovation and speciation in the family
      Corynebacteriaceae: A phylogenomics approach.
AB  - The pangenome of a bacterial species population is formed by genetic reduction
      and genetic expansion over the long course of evolution. Gene loss is a pervasive
      source of genetic reduction, and (exogenous and endogenous) gene gain is the main
      driver of genetic expansion. To understand the genetic innovation and speciation
      of the family Corynebacteriaceae, which cause a wide range of serious infections
      in humans and animals, we analyzed the pangenome of this family, and
      reconstructed its phylogeny using a phylogenomics approach. Genetic variations
      have occurred throughout the whole evolutionary history of the
      Corynebacteriaceae. Gene loss has been the primary force causing genetic changes,
      not only in terms of the number of protein families affected, but also because of
      its continuity on the time series. The variation in metabolism caused by these
      genetic changes mainly occurred for membrane transporters, two-component systems,
      and metabolism related to amino acids and carbohydrates. Interestingly,
      horizontal gene transfer (HGT) not only caused changes related to pathogenicity,
      but also triggered the acquisition of antimicrobial resistance. The Darwinian
      theory of evolution did not adequately explain the effects of dispersive HGT
      and/or gene loss in the evolution of the Corynebacteriaceae. These findings
      provide new insight into the evolution and speciation of Corynebacteriaceae and
      advance our understanding of the genetic innovation in microbial populations.

PMID- 27864137
TI  - Intergenomic evolution and metabolic cross-talk between rumen and thermophilic
      autotrophic methanogenic archaea.
AB  - Methanobrevibacter ruminantium M1 (MRU) is a rumen methanogenic archaean that can
      be able to utilize formate and CO2/H2 as growth substrates. Extensive analysis on
      the evolutionary genomic contexts considered herein to unravel its intergenomic
      relationship and metabolic adjustment acquired from the genomic content of
      Methanothermobacter thermautotrophicus DeltaH. We demonstrated its intergenomic
      distance, genome function, synteny homologs and gene families, origin of
      replication, and methanogenesis to reveal the evolutionary relationships between
      Methanobrevibacter and Methanothermobacter. Comparison of the phylogenetic and
      metabolic markers was suggested for its archaeal metabolic core lineage that
      might have evolved from Methanothermobacter. Orthologous genes involved in its
      hydrogenotrophic methanogenesis might be acquired from intergenomic ancestry of
      Methanothermobacter via Methanobacterium formicicum. Formate dehydrogenase
      (fdhAB) coding gene cluster and carbon monoxide dehydrogenase (cooF) coding gene
      might have evolved from duplication events within Methanobrevibacter
      Methanothermobacter lineage, and fdhCD gene cluster acquired from bacterial
      origins. Genome-wide metabolic survey found the existence of four novel pathways
      viz. l-tyrosine catabolism, mevalonate pathway II, acyl-carrier protein
      metabolism II and glutathione redox reactions II in MRU. Finding of these
      pathways suggested that MRU has shown a metabolic potential to tolerate molecular
      oxygen, antimicrobial metabolite biosynthesis and atypical lipid composition in
      cell wall, which was acquainted by metabolic cross-talk with mammalian bacterial
      origins. We conclude that coevolution of genomic contents between
      Methanobrevibacter and Methanothermobacter provides a clue to understand the
      metabolic adaptation of MRU in the rumen at different environmental niches.

PMID- 27864138
TI  - Sarniensine, a mesembrine-type alkaloid isolated from Nerine sarniensis, an
      indigenous South African Amaryllidaceae, with larvicidal and adulticidal
      activities against Aedes aegypti.
AB  - A new mesembrine-type alkaloid, named sarniensine, was isolated together with
      tazettine, lycorine, the main alkaloid, and 3-epimacronine from Nerine
      sarniensis, with the last two produced for the first time by this plant. This
      Amaryllidaceae, which is indigenous of South Africa, was investigated for its
      alkaloid content, because the organic extract of its bulbs showed strong
      larvicidal activity with an LC50 value of 0.008MUgMUL-1 against first instar
      Aedes aegypti larvae and with an LD50 value 4.6MUg/mosquito against adult female
      Ae. aegypti, which is the major vector for dengue, yellow fever and the Zika
      virus. The extract did not show repellency at MED value of 0.375mgcm2 against
      adult Ae. aegypti. Sarniensine was characterized using spectroscopic and
      chiroptical methods as (3aR,4Z,6S,7aS)-6-methoxy-3a-(2'-methoxymethyl-benzo
      [1,3]dioxol-1'-yl)-1-methyl-2,3,3a,6,7,7a-hexahydro-1H-indole. It was less
      effective against larva at the lowest concentration of 0.1MUgMUL-1, however it
      showed strong adulticidal activity with an LD50 value of 1.38+/-0.056MUgmosquito
      1.

PMID- 27864139
TI  - Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive
      sleep apnea red blood cells: Correlation with polysomnographic and metabolic
      parameters.
AB  - We have examined the effects of Obstructive Sleep Apnea (OSA) on red blood cell
      (RBC) proteome variation at evening/morning day time to uncover new insights into
      OSA-induced RBC dysfunction that may lead to OSA manifestations. Dysregulated
      proteins mainly fall in the group of catalytic enzymes, stress response and redox
      regulators such as peroxiredoxin 2 (PRDX2). Validation assays confirmed that at
      morning the monomeric/dimeric forms of PRDX2 were more overoxidized in OSA RBC
      compared to evening samples. Six month of positive airway pressure (PAP)
      treatment decreased this overoxidation and generated multimeric overoxidized
      forms associated with chaperone/transduction signaling activity of PRDX2. Morning
      levels of overoxidized PRDX2 correlated with polysomnographic (PSG)-arousal index
      and metabolic parameters whereas the evening level of disulfide-linked dimer
      (associated with peroxidase activity of PRDX2) correlated with PSG parameters.
      After treatment, morning overoxidized multimer of PRDX2 negatively correlated
      with fasting glucose and dopamine levels. Overall, these data point toward severe
      oxidative stress and altered antioxidant homeostasis in OSA RBC occurring mainly
      at morning time but with consequences till evening. The beneficial effect of PAP
      involves modulation of the redox/oligomeric state of PRDX2, whose mechanism and
      associated chaperone/transduction signaling functions deserves further
      investigation. RBC PRDX2 is a promising candidate biomarker for OSA severity and
      treatment monitoring, warranting further investigation and validation.

PMID- 27864140
TI  - The role of miR-190a in methylglyoxal-induced insulin resistance in endothelial
      cells.
AB  - Methylglyoxal (MGO) is a reactive dicarbonyl produced as by-product of
      glycolysis, and its formation is heightened in hyperglycaemia. MGO plasma levels
      are two-fold to five-fold increased in diabetics and its accumulation promotes
      the progression of vascular complications. Impairment of endothelium-derived
      nitric oxide represents a common feature of endothelial dysfunction in diabetics.
      We previously demonstrated that MGO induces endothelial insulin resistance.
      Increasing evidence shows that high glucose and MGO modify vascular expression of
      several microRNAs (miRNAs), suggesting their potential role in the impairment of
      endothelial insulin sensitivity. The aim of the study is to investigate whether
      miRNAs may be involved in MGO-induced endothelial insulin resistance in
      endothelial cells. MGO reduces the expression of miR-190a both in mouse aortic
      endothelial cells (MAECs) and in aortae from mice knocked-down for glyoxalase-1.
      miR-190a inhibition impairs insulin sensitivity, whereas its overexpression
      prevents the MGO-induced insulin resistance in MAECs. miR-190a levels are not
      affected by the inhibition of ERK1/2 phosphorylation. Conversely, ERK1/2
      activation is sustained by miR-190a inhibitor and the MGO-induced ERK1/2 hyper
      activation is reduced by miR-190a mimic transfection. Similarly, protein levels
      of the upstream KRAS are increased by both MGO and miR-190a inhibitor, and these
      levels are reduced by miR-190a mimic transfection. Interestingly, silencing of
      KRAS is able to rescue the MGO-impaired activation of IRS1/Akt/eNOS pathway in
      response to insulin. In conclusion, miR-190a down-regulation plays a role in MGO
      induced endothelial insulin resistance by increasing KRAS. This study highlights
      miR-190a as new candidate for the identification of strategies aiming at
      ameliorating vascular function in diabetes.

PMID- 27864141
TI  - Long-term inhibition of cyclophilin D results in intracellular translocation of
      calcein AM from mitochondria to lysosomes.
AB  - Cyclophilin D is a peptidyl-prolyl cis-trans isomerase localized in the
      mitochondrial matrix. Although its effects on mitochondrial characteristics have
      been well studied, its relation to the uptake of molecules by mitochondria
      remains unknown. Here, we demonstrated the effects of cyclophilin D on the
      intracellular translocation of calcein AM. Following addition of calcein AM to
      control cells or cells overexpressing wild-type cyclophilin D, calcein
      fluorescence was observed in mitochondria. However, long-term inhibition of
      cyclophilin D in these cells altered the localization of calcein fluorescence
      from mitochondria to lysosomes without changing mitochondrial esterase activity.
      In addition, depletion of glucose from the medium recovered calcein localization
      from lysosomes to mitochondria. This is the first demonstration of the effects of
      cyclophilin D on the intracellular translocation of molecules other than proteins
      and suggests that cyclophilin D may modify mitochondrial features by inducing the
      translocation of molecules to the mitochondria through the mechanism associated
      with cellular energy metabolism.

PMID- 27864142
TI  - Glycogen storage disease type Ib neutrophils exhibit impaired cell adhesion and
      migration.
AB  - Glycogen storage disease type Ib (GSD-Ib), characterized by impaired glucose
      homeostasis, neutropenia, and neutrophil dysfunction, is an inherited autosomal
      recessive disorder caused by a deficiency in the glucose-6-phosphate transporter
      (G6PT). Neutrophils play an essential role in the defense against invading
      pathogens. The recruitment of neutrophils towards the inflammation sites in
      response to inflammatory stimuli is a tightly regulated process involving
      rolling, adhesion, and transmigration. In this study, we investigated the role of
      G6PT in neutrophil adhesion and migration using in vivo and in vitro models. We
      showed that the GSD-Ib (G6pt-/-) mice manifested severe neutropenia in both blood
      and bone marrow, and treating G6pt-/- mice with granulocyte colony-stimulating
      factor (G-CSF) corrected neutropenia. However, upon thioglycolate challenge,
      neutrophils from both untreated and G-CSF-treated G6pt-/-mice exhibited decreased
      ability to migrate to the peritoneal cavity. In vitro migration and cell adhesion
      of G6PT-deficient neutrophils were also significantly impaired. Defects in cell
      migration were not due to enhanced apoptosis or altered fMLP receptor expression.
      Remarkably, the expression of the beta2 integrins CD11a and CD11b, which are
      critical for cell adhesion, was greatly decreased in G6PT-deficient neutrophils.
      This study suggests that deficiencies in G6PT cause impairment in neutrophil
      adhesion and migration via aberrant expression of beta2 integrins, and our
      finding should facilitate the development of novel therapies for GSD-Ib.

PMID- 27864144
TI  - Transcriptional regulation of microsomal prostaglandin E synthase 1 by the proto
      oncogene, c-myc, in the pathogenesis of inflammation and cancer.
AB  - Pro-inflammatory molecules play a key role in the progression of various types of
      cancers highlighting the importance of studying the pathways that regulate the
      inflammatory cytokine production. To this end, prostaglandins have been reported
      to correlate with exacerbated cancer phenotypes that may be prevented by using
      anti-inflammatory drugs in humans. To understand how the prostaglandin E synthase
      1 (mPGES1) may be regulated we analyzed its promoter sequence and identified myc
      binding sites. Functional validation was performed by mutating the sites that led
      to attenuated promoter activation of mPGES1. The known c-myc inhibitor (10058-F4)
      also blocked PGE2 activity, indicating the importance of c-Myc in PGE2 synthesis.
      Isocoumarin analogs were able to reduce the expressions of both c-myc as well as
      mPGES1 and also inhibit the production of PGE2. Based on these data and the well
      established role of c-myc in oncogenesis, we have demonstrated an additional role
      of c-myc in exacerbating cancers via PGE2 production, which may provide a
      therapeutic opportunity to treat these diseases.

PMID- 27864143
TI  - C14orf93 (RTFC) is identified as a novel susceptibility gene for familial
      nonmedullary thyroid cancer.
AB  - The genetic causes for familial nonmedullary thyroid cancer (FNMTC) remain
      largely unknown. Through genetic linkage analysis and exome sequencing, C14orf93
      (RTFC), PYGL, and BMP4 were identified as susceptibility gene candidates in a
      FNMTC family. By examining the expression and the oncogenic functions of these
      candidate genes, PYGL and BMP4 were excluded. We further characterized the
      functions of the uncharacterized gene RTFC in thyroid cancer. RTFC promotes
      thyroid cancer cell survival under starving conditions, and thyroid cancer cell
      migration. The R115Q, V205M and G209D RTFC mutants enhance the colony forming
      capacity of thyroid cancer cells, and are able to transform normal thyroid cells.
      In summary, our data suggest the roles of RTFC in thyroid carcinogenesis.

PMID- 27864145
TI  - MyD88 NEDDylation negatively regulates MyD88-dependent NF-kappaB signaling
      through antagonizing its ubiquitination.
AB  - Myeloid differentiation factor 88 (MyD88) plays a central role in innate immunity
      response, however, how its activity is tightly regulated remains largely unknown.
      In this study, we identify MyD88 as a novel substrate of NEDD8, and demonstrate
      that MyD88 NEDDylation antagonizes its ubiquitination. Interestingly, in response
      to the stimulation of IL-1beta, MyD88 NEDDylation is downregulated while its
      ubiquitination is upregulated. We also show that deNEDDylase NEDP1 serves as a
      regulator of this process. Furthermore, we demonstrate that NEDD8 negatively
      regulates the dimerization of MyD88 and suppresses MyD88-dependent NF-kappaB
      signaling. Taken together, this study reveals that NEDDylation of MyD88 regulates
      NF-kappaB activity through antagonizing its ubiquitination, suggesting a novel
      mechanism of modulating NF-kappaB signaling pathway.

PMID- 27864146
TI  - MicroRNA-187 regulates gastric cancer progression by targeting the tumor
      suppressor CRMP1.
AB  - Aberrant expression of microRNAs contributes to the initiation and progression of
      numerous human cancers. The underlying effects and molecular mechanisms of
      microRNA-187 (miR-187) in gastric cancer (GC) remain unclear. The present study
      reports that miR-187 was significantly overexpressed in GC tissues compared to
      that in non-tumor tissues and was associated with malignant clinical factors such
      as depth of invasion (P = 0.005), tumor size (P = 0.024), lymph node metastasis
      (P = 0.048), and TNM stage (P = 0.035). Additionally, miR-187 promoted tumor
      growth in vivo, and significantly increased migration, invasion, and
      proliferation, but inhibited apoptosis in GC cells. It was found that collapsin
      response mediator protein 1 (CRMP1), a tumor suppressor, was a direct downstream
      target of miR-187 in GC. Furthermore, CRMP1 silencing resulted in similar effects
      on cell proliferation, migration, and apoptosis as those of miR-187
      overexpressing GC cells. Additionally, the effects of miR-187 inhibitor on cell
      migration and cell apoptosis were reversed by CRMP1 downregulation. In summary,
      miR-187 promotes tumor progression by regulating CRMP1 expression in GC and may
      thus be a potential prognostic marker and a therapeutic target in GC.

PMID- 27864147
TI  - Host factor PRPF31 is involved in cccDNA production in HBV-replicating cells.
AB  - Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a central
      role in chronic HBV infection and replication, and is an important factor for HBV
      surface antigen loss indicating the endpoint of HBV treatment. However, there is
      a known problem that current anti-HBV drugs, including interferons and
      nucleos(t)ide analogues, reduce HBV replication but have a little or no effect on
      reducing cccDNA. Therefore, the development of new therapeutic agents is
      necessary to eradicate cccDNA. In this study, we identified pre-mRNA processing
      factor 31 (PRPF31) by siRNA screening as a factor associated with cccDNA. PRPF31
      knockdown by siRNA decreased cccDNA formation without serious cytotoxicity. In
      rescue experiments, expression of siRNA-resistant PRPF31 recovered cccDNA
      formation. PRPF31 knockdown did not affect HBV core protein and HBV core DNA
      levels in HBV-replicating cells. Chromatin immunoprecipitation and
      immunoprecipitation assays revealed an association between PRPF31 and cccDNA.
      Furthermore, co-overexpression of PRPF31 and HBx enhanced cccDNA formation in
      HepAD38 cells. Taken together, the present findings suggest that the interaction
      between PRPF31 and HBx may be a novel target for anti-HBV treatment.

PMID- 27864148
TI  - Three pentraxins C-reactive protein, serum amyloid p component and pentraxin 3
      mediate complement activation using Collectin CL-P1.
AB  - BACKGROUND: Pentraxins (PTXs) are a superfamily of multifunctional conserved
      proteins involved in acute-phase responses. Recently, we have shown that
      collectin placenta 1 (CL-P1) and C-reactive protein (CRP) mediated complement
      activation and failed to form terminal complement complex (TCC) in normal serum
      conditions because of complement factor H inhibition. METHODS: We used CL-P1
      expressing CHO/ldlA7 cells to study the interaction with PTXs. Soluble type CL-P1
      was used in an ELISA assay for the binding, C3 and TCC deposition experiments.
      Furthermore, we used our previously established CL-P1 expressing HEK293 cells for
      the C3 fragment and TCC deposition assay. RESULTS: We demonstrated that CL-P1
      also bound serum amyloid p component (SAP) and pentraxin 3 (PTX3) to activate the
      classical pathway and the alternative pathway using factor B. CRP and PTX3
      further amplified complement deposition by properdin. We found that CRP and PTX3
      recruit CFH, whereas SAP recruits C4 binding protein on CL-P1 expressing cell
      surfaces to prevent the formation of TCC in normal serum conditions. In addition,
      depletion of CFH, C4BP and complement factor I (CFI) failed to prevent TCC
      formation both in ELISA and cell experiments. Furthermore, soluble complement
      receptor 1, an inhibitor of all complement pathways prevents PTX induced TCC
      formation. CONCLUSION: Our current study hypothesizes that the interaction of
      pentraxins with CL-P1 is involved in complement activation. GENERAL SIGNIFICANCE:
      CL-P1 might generally inhibit PTX induced complement activation and host damage
      to protect self-tissues.

PMID- 27864149
TI  - Mechanistic insight into the procoagulant activity of tumor-derived apoptotic
      vesicles.
AB  - BACKGROUND: Chemotherapy induces the release of apoptotic vesicles (ApoV) from
      the tumor plasma membrane. Tumor ApoV may enhance the risk of thrombotic events
      in cancer patients undergoing chemotherapy. However, the relative contribution of
      ApoV to coagulation and the pathways involved remain poorly characterized. In
      addition, this study sets out to compare the procoagulant activity of
      chemotherapy-induced ApoV with their cell of origin and to determine the
      mechanisms of ApoV-induced coagulation. METHODS: We utilized human and murine
      cancer cell lines and chemotherapeutic agents to determine the requirement for
      the coagulation factors (tissue factor; TF, FII, FV, FVII, FVIII, FIX and
      phosphatidylserine) in the procoagulant activity of ApoV. The role of previously
      identified ApoV-associated FV was determined in a FV functional assay. RESULTS:
      ApoV were significantly more procoagulant per microgram of protein compared to
      parental living or dying tumor cells. In the phase to peak fibrin generation,
      procoagulant activity was dependent on phosphatidylserine, TF expression, FVII
      and the prothrombinase complex. However, the intrinsic coagulation factors FIX
      and FVIII were dispensable. ApoV-associated FV could not support coagulation in
      the absence of supplied, exogenous FV. CONCLUSIONS: ApoV are significantly more
      procoagulant than their parental tumor cells. ApoV require the extrinsic tenase
      and prothrombinase complex to activate the early phase of coagulation. Endogenous
      FV identified on tumor ApoV is serum-derived and functional, but is non-essential
      for ApoV-mediated fibrin generation. GENERAL SIGNIFICANCE: This study clarifies
      the mechanisms of procoagulant activity of vesicles released from dying tumor
      cells.

PMID- 27864150
TI  - Effect of malondialdehyde on the ovalbumin structure and its interactions with
      T84 epithelial cells.
AB  - BACKGROUND: Protein oxidation can occur as a consequence of lipid peroxidation
      during food processing. The aim of this work was to explore the effect of
      malondialdehyde (MDA) modification of ovalbumin (OVA) on its interaction with T84
      intestinal cells. METHODS: Molecular dynamics simulation was employed for the
      prediction of MDA modification in the OVA, while introduced structural changes
      were evaluated by measurement of carbonyl group content, fluorescence spectra,
      MS/MS analysis, and IgE reactivity. Effects of MDA modified OVA on T84 epithelial
      cells were analyzed by gene expression for pro-inflammatory cytokines and protein
      secretion. RESULTS: Out of 9 predicted, five modified Lys residues were confirmed
      by MS/MS analysis: 51TQINKVVR58, 85DILNQITKPNDVYSFSLASR104,
      111YPILPEYLQCVKELYR126, 187AFKDEDTQAMPFR199, 277KIKVYLPR284, and 278IKVYLPR284.
      The introduced MDA modifications influenced profile of IgE reactivity to OVA.
      Treatment of T84 epithelial cells with OVA and OVA modified with 1mM MDA, induced
      up-regulation of pro-inflammatory cytokines (IL-1beta, IL-25, IL-33, TSLP and
      TNFalpha), while OVA modification with 10mM MDA induced down regulation of the
      cytokine expression profile, except for IL-1beta. OVA and OVA modified with 1mM
      MDA induced secretion of epithelial cells specific cytokine IL-33. CONCLUSIONS:
      This finding indicated that OVA and its MDA modified form have the potential to
      trigger the innate immunity by inducing up-regulation and secretion of pro
      allergenic IL-33 in T84 intestinal epithelial cells. GENERAL SIGNIFICANCE:
      Interactions of ovalbumin and its MDA modified form with intestinal epithelial
      cells can induce a specific immunological priming necessary for the downstream
      activation of innate immunity.

PMID- 27864151
TI  - Gelatin/nanoceria nanocomposite fibers as antioxidant scaffolds for neuronal
      regeneration.
AB  - BACKGROUND: The design of efficient nerve conduits able to sustain the axonal
      outgrowth and its guidance towards appropriate targets is of paramount importance
      in nerve tissue engineering. METHODS: In this work, we propose the preparation of
      highly aligned nanocomposite fibers of gelatin/cerium oxide nanoparticles
      (nanoceria), prepared by electrospinning. Nanoceria are powerful self
      regenerative antioxidant nanomaterials, that behave as strong reactive oxygen
      species scavengers, and among various beneficial effects, they have been proven
      to inhibit the cell senescence and to promote the neurite sprouting. RESULTS:
      After a detailed characterization of the developed substrates, they have been
      tested on neuron-like SH-SY5Y cells, demonstrating strong antioxidant properties
      and beneficial multi-cue effects in terms of neurite development and alignment.
      CONCLUSIONS: Obtained findings suggest efficiency of the proposed substrates in
      providing combined topographical stimuli and antioxidant effects to cultured
      cells. GENERAL SIGNIFICANCE: Proposed nanocomposite scaffolds represent a
      promising approach for nerve tissue engineering and regenerative medicine.

PMID- 27864153
TI  - Immunogenicity of murine mPEG-red blood cells and the risk of anti-PEG antibodies
      in human blood donors.
AB  - The immunocamouflage of non-ABO blood group antigens by membrane-grafted
      methoxypoly(ethylene glycol) (mPEG) may attenuate the risk of red blood cell
      (RBC) alloimmunization. However, concerns have been raised over the immunogenic
      risk of PEG and PEG-RBCs. To assess this risk, murine and human studies were
      performed. Mice were exposed to soluble PEG prior to, or between, multiple
      transfusions (~60-day intervals) of control or mPEG-RBCs, and cell survival was
      determined by flow cytometry. In some studies, the control and mPEG-RBC groups
      were reversed after one or more transfusions. Furthermore, human blood donors and
      commercial intravenous immunoglobulin products were examined to detect anti-PEG
      antibodies and to assess the risk for false positives. Naive mice receiving
      chronic mPEG-RBC transfusions had normal RBC survival curves with no evidence of
      anti-PEG antibodies. Similarly, challenge with soluble PEG did not elicit anti
      PEG antibodies in mice. Studies in humans revealed no evidence of a high
      prevalence of anti-PEG antibodies in either blood donors or commercial
      intravenous immunoglobulin. However, by use of the methods employed by studies
      identifying high levels of anti-PEG antibodies, a significant level (~15%) of
      "false positives" were detected in commercial antibodies of known (non-PEG)
      specificities. These findings suggest that methodologic problems yielded a high
      rate of false positives in these earlier studies. These data continue to support
      the clinical utility of cellular PEGylation and the low immunogenic risk of
      grafted mPEG.

PMID- 27864152
TI  - The flavinyl transferase ApbE of Pseudomonas stutzeri matures the NosR protein
      required for nitrous oxide reduction.
AB  - The copper-containing enzyme nitrous oxide reductase (N2OR) catalyzes the
      transformation of nitrous oxide (N2O) to dinitrogen (N2) in microbial
      denitrification. Several accessory factors are essential for assembling the two
      copper sites CuA and CuZ, and for maintaining the activity. In particular, the
      deletion of either the transmembrane iron-sulfur flavoprotein NosR or the
      periplasmic protein NosX, a member of the ApbE family, abolishes N2O respiration.
      Here we demonstrate through biochemical and structural studies that the ApbE
      protein from Pseudomonas stutzeri, where the nosX gene is absent, is a monomeric
      FAD-binding protein that can serve as the flavin donor for NosR maturation via
      covalent flavinylation of a threonine residue. The flavin transfer reaction
      proceeds both in vivo and in vitro to generate post-translationally modified NosR
      with covalently bound FMN. Only FAD can act as substrate and the reaction
      requires a divalent cation, preferably Mg2+ that was also present in the crystal
      structure. In addition, the reaction is species-specific to a certain extent.

PMID- 27864154
TI  - Root cause analysis of limitations of virtual crossmatch for kidney allocation to
      highly-sensitized patients.
AB  - Efficient allocation of deceased donor organs depends upon effective prediction
      of immunologic compatibility based on donor HLA genotype and recipient
      alloantibody profile, referred to as virtual crossmatching (VCXM). VCXM has
      demonstrated utility in predicting compatibility, though there is reduced
      efficacy for patients highly sensitized against allogeneic HLA antigens. The
      recently revised deceased donor kidney allocation system (KAS) has increased
      transplantation for this group, but with an increased burden for
      histocompatibility testing and organ sharing. Given the limitations of VCXM, we
      hypothesized that increased organ offers for highly-sensitized patients could
      result in a concomitant increase in offers rejected due to unexpectedly positive
      crossmatch. Review of 645 crossmatches performed for deceased donor kidney
      transplantation at our center did not reveal a significant increase in positive
      crossmatches following KAS implementation. Positive crossmatches not predicted by
      VCXM were concentrated among highly-sensitized patients. Root cause analysis of
      VCXM failures identified technical limitations of anti-HLA antibody testing as
      the most significant contributor to VCXM error. Contributions of technical
      limitations including additive/synergistic antibody effects, prozone phenomenon,
      and antigens not represented in standard testing panels, were evaluated by
      retrospective testing. These data provide insight into the limitations of VCXM,
      particularly those affecting allocation of kidneys to highly-sensitized patients.

PMID- 27864155
TI  - Minimally Invasive Whipple's Technique for Laparoscopic-Assisted Pylorus
      Preserving Pancreaticoduodenectomy.

PMID- 27864156
TI  - Neurocognitive predictors of treatment response to randomized treatment in adults
      with tic disorders.
AB  - Tourette's disorder (TS) and chronic tic disorder (CTD) are neurodevelopmental
      disorders characterized by involuntary vocal and motor tics. Consequently, TS/CTD
      have been conceptualized as disorders of cognitive and motor inhibitory control.
      However, most neurocognitive studies have found comparable or superior inhibitory
      capacity among individuals with TS/CTD relative to healthy controls. These
      findings have led to the hypothesis that individuals with TS/CTD develop
      increased inhibitory control due to the constant need to inhibit tics. However,
      the role of cognitive control in TS/CTD is not yet understood, particularly in
      adults. To examine the role of inhibitory control in TS/CTD, the present study
      investigated this association by assessing the relationship between inhibitory
      control and treatment response in a large sample of adults with TS/CTD. As part
      of a large randomized trial comparing behavior therapy versus supportive
      psychotherapy for TS/CTD, a battery of tests, including tests of inhibitory
      control was administered to 122 adults with TS/CTD at baseline. We assessed the
      association between neuropsychological test performance and change in symptom
      severity, as well as compared the performance of treatment responders and non
      responders as defined by the Clinical Global Impression Scale. Results indicated
      that change in symptoms, and treatment response were not associated with
      neuropsychological performance on tests of inhibitory control, intellectual
      ability, or motor function, regardless of type of treatment. The finding that
      significant change in symptom severity of TS/CTD patients is not associated with
      impairment or change in inhibitory control regardless of treatment type suggests
      that inhibitory control may not be a clinically relevant facet of these disorders
      in adults.

PMID- 27864157
TI  - The effect of feed-based vaccination on tilapia farm endemic for streptococcosis.
AB  - A tilapia farm experiencing endemic streptococcosis was selected to study the
      effect of vaccination with a feed-based vaccine on naturally ocurring
      streptococcosis. A total of 9000 red tilapia, Oreochromis niloticus * Oreochromis
      mossambicus of 100 +/- 20 g were divided into 9 cages. Fish of Group 1 in cages
      1, 2 and 3 were not vaccinated. Group 2 in cages 4, 5 and 6 were vaccinated on
      days 0 and 14 (single booster) while Group 3 in cages 7, 8 and 9 were vaccinated
      on days 0, 14 and 42 (double booster). Vaccination was done by oral
      administration of the feed-based bacterin vaccine at 4% bodyweight. Samples of
      serum for antibody study and the brain, eyes and kidney for bacterial isolation
      were collected at 14-day intervals. The study was carried out during the critical
      months between April and June. Following vaccination and booster, there was
      significant (p < 0.05) increase in the antibody levels in all vaccinated groups
      from week 1 that reached the peak at week 3 before declining gradually until week
      6. However, second booster on week 6 significantly (p < 0.05) increased the
      antibody level that remained high until the end of the 16-week study period
      (double booster). Streptococcus agalactiae was isolated at the start of the
      experiment (day 0) at an average of 10 +/- 5.0% of the sampled fish. In week 4,
      the isolation rate was 13 +/- 5.7% but increased to 18 +/- 7.6% in week 8, to 25
      +/- 10.0% in week 10, to 28 +/- 5.8% in week 12 and 25 +/- 7.3% in week 14. The
      average isolation rate was 28 +/- 7.2%, 18 +/- 7.1% and 13 +/- 8.2% of the fish
      sampled from unvaccinated, single booster and double booster groups,
      respectively. At the end of the study period, the survival rate was 45.2 +/-
      2.45% for unvaccinated, 65.3 +/- 4.8% for single booster and 75.1 +/- 2.1% for
      double booster groups. Vaccinating fish in endemic farm might not eliminate the
      disease but was able to significantly improve the survival rate.

PMID- 27864158
TI  - Feeding of nano scale oats beta-glucan enhances the host resistance against
      Edwardsiella tarda and protective immune modulation in zebrafish larvae.
AB  - In this study, we prepared and characterized the oats origin of nano scale beta
      glucan (NBG) and investigated the immunomodulatory properties in zebrafish
      larvae. Newly prepared NBG (average particle size of 465 nm) was fully soluble in
      water. Zebrafish larvae survival rate was increased against pathogenic bacteria
      Edwardsiella tarda, when NBG was added to the water (500 MUg/mL) compared to NBG
      non-exposed controls. Moreover, quantitative real time PCR (qRT-PCR) results
      showed up-regulation of immune functional genes including TNF-alpha, IL-1beta,
      beta-defensin, lysozyme, IL 10, IL 12 and C-Rel indicating higher survival rate
      could be due to stronger immunomodulatory function of NBG (500 MUg/mL). Thus, non
      toxic, water soluble and biodegradable NBG from oats could be considered as the
      potential immunostimulant for larval aquaculture.

PMID- 27864159
TI  - High-level expression and efficient refolding of therapeutically important
      recombinant human Interleukin-3 (hIL-3) in E. coli.
AB  - Human interleukin-3 (hIL-3) is a pleiotropic cytokine that stimulates the
      differentiation and proliferation of multipotent hematopoietic cells thus making
      it a therapeutically important molecule. In this study, its poor expression yield
      was improved by addressing various upstream bottlenecks in E. coli heterologous
      system. The codon-optimized hIL-3 gene was cloned under various signal sequences
      and solubility enhancer fusion tags for its hyper-expression under a strong T7
      promoter. The optimization of shake flask expression studies resulted in a hIL-3
      protein concentration of 225 mg/L in the form of inclusion bodies (IBs). Lowering
      of inducer concentration and cultivation temperature did not improve its
      solubility. The hIL-3 protein was refolded from IBs and resulted a protein
      recovery yield of 53% after optimization of refolding conditions. The refolded
      protein was subsequently purified using Ni-NTA affinity chromatography and gave
      ~95% pure protein. The conformational properties of the refolded hIL-3 protein
      were studied by CD and fluorescence spectrometry where protein showed 40% alpha
      helix and 12% beta-sheets with a fluorescence emission maxima at 344 nm. The
      molecular identity was further confirmed by MALDI-TOF/TOF and western blot
      analysis. The biological activity of refolded protein was confirmed via cell
      proliferation assay on human erythroleukemia TF-1 cells where commercial hIL-3
      was taken as a standard control.

PMID- 27864160
TI  - Blotting-free and lossless cryo-electron microscopy grid preparation from
      nanoliter-sized protein samples and single-cell extracts.
AB  - We present a sample preparation method for cryo-electron microscopy (cryo-EM)
      that requires only 3-20nL of sample to prepare a cryo-EM grid, depending on the
      protocol used. The sample is applied and spread on the grid by a microcapillary.
      The procedure does not involve any blotting steps, and real-time monitoring
      allows the water film thickness to be assessed and decreased to an optimum value
      prior to vitrification. We demonstrate that the method is suitable for high
      resolution cryo-EM and will enable alternative electron microscopy approaches,
      such as single-cell visual proteomics.

PMID- 27864162
TI  - Aging: Treating the Older Patient.

PMID- 27864161
TI  - Maintenance versus Induction Therapy Choice on Outcomes after Autologous
      Transplantation for Multiple Myeloma.
AB  - Bortezomib (V), lenalidomide (R), cyclophosphamide (C), and dexamethasone (D) are
      components of the most commonly used modern doublet (RD, VD) or triplet (VRD,
      CVD) initial induction regimens before autologous hematopoietic cell
      transplantation (AHCT) for multiple myeloma (MM) in the United States. In this
      study we evaluated 693 patients receiving "upfront" AHCT after initial induction
      therapy with modern doublet or triplet regimens using data reported to the Center
      for International Blood and Marrow Transplant Research from 2008 to 2013.
      Analysis was limited to those receiving a single AHCT after 1 line of induction
      therapy within 12 months from treatment initiation for MM. In multivariate
      analysis, progression-free survival (PFS) and overall survival were similar
      irrespective of induction regimen. However, high-risk cytogenetics and nonreceipt
      of post-transplant maintenance/consolidation therapy were associated with higher
      risk of relapse. Patients receiving post-transplant therapy had significantly
      improved 3-year PFS versus no post-transplant therapy (55% versus 39%, P =
      .0001). This benefit was most evident in patients not achieving at least a
      complete response post-AHCT (P = .005). In patients receiving upfront AHCT, the
      choice of induction regimen (doublet or triplet therapies) appears to be of lower
      impact than use of post-transplant therapy.

PMID- 27864163
TI  - Developing a Web-Based Weight Management Program for Childhood Cancer Survivors:
      Rationale and Methods.
AB  - BACKGROUND: Due to advances in the field of oncology, survival rates for children
      with cancer have improved significantly. However, these childhood cancer
      survivors are at a higher risk for obesity and cardiovascular diseases and for
      developing these conditions at an earlier age. OBJECTIVE: In this paper, we
      describe the rationale, conceptual framework, development process, novel
      components, and delivery plan of a behavioral intervention program for preventing
      unhealthy weight gain in survivors of childhood acute lymphoblastic leukemia
      (ALL). METHODS: A Web-based program, the Healthy Eating and Active Living (HEAL)
      program, was designed by a multidisciplinary team of researchers who first
      identified behaviors that are appropriate targets for weight management in
      childhood ALL survivors and subsequently developed the intervention components,
      following core behavioral change strategies grounded in social cognitive and self
      determination theories. RESULTS: The Web-based HEAL curriculum has 12 weekly self
      guided sessions to increase parents' awareness of the potential impact of cancer
      treatment on weight and lifestyle habits and the importance of weight management
      in survivors' long-term health. It empowers parents with knowledge and skills on
      parenting, nutrition, and physical activity to help them facilitate healthy
      eating and active living soon after the child completes intensive cancer
      treatment. Based on social cognitive theory, the program is designed to increase
      behavioral skills (goal-setting, self-monitoring, and problem-solving) and self
      efficacy and to provide positive reinforcement to sustain behavioral change.
      CONCLUSIONS: Lifestyle interventions are a priority for preventing the early
      onset of obesity and cardiovascular risk factors in childhood cancer survivors.
      Intervention programs need to meet survivors' targeted behavioral needs, address
      specific barriers, and capture a sensitive window for behavioral change. In
      addition, they should be convenient, cost-effective and scalable. Future studies
      are needed to evaluate the feasibility of introducing weight management early in
      cancer care and the efficacy of early weight management on survivors' health
      outcomes.

PMID- 27864164
TI  - Perceptions Toward a Smoking Cessation App Targeting LGBTQ+ Youth and Young
      Adults: A Qualitative Framework Analysis of Focus Groups.
AB  - BACKGROUND: The prevalence of smoking among lesbian, gay, bisexual, trans, queer,
      and other sexual minority (LGBTQ+) youth and young adults (YYA) is significantly
      higher compared with that among non-LGBTQ+ persons. However, in the past,
      interventions were primarily group cessation classes that targeted LGBTQ+ persons
      of all ages. mHealth interventions offer an alternate and modern intervention
      platform for this subpopulation and may be of particular interest for young
      LGBTQ+ persons. OBJECTIVE: This study explored LGBTQ+ YYA (the potential users')
      perceptions of a culturally tailored mobile app for smoking cessation.
      Specifically, we sought to understand what LGBTQ+ YYA like and dislike about this
      potential cessation tool, along with how such interventions could be improved.
      METHODS: We conducted 24 focus groups with 204 LGBTQ+ YYA (aged 16-29 years) in
      Toronto and Ottawa, Canada. Participants reflected on how an app might support
      LGBTQ+ persons with smoking cessation. Participants indicated their feelings,
      likes and dislikes, concerns, and additional ideas for culturally tailored
      smoking cessation apps. Framework analysis was used to code transcripts and
      identify the overarching themes. RESULTS: Study findings suggested that LGBTQ+
      YYA were eager about using culturally tailored mobile apps for smoking cessation.
      Accessibility, monitoring and tracking, connecting with community members,
      tailoring, connecting with social networks, and personalization were key reasons
      that were valued for a mobile app cessation program. However, concerns were
      raised about individual privacy and that not all individuals had access to a
      mobile phone, users might lose interest quickly, an app would need to be marketed
      effectively, and app users might cheat and lie about progress to themselves.
      Participants highlighted that the addition of distractions, rewards,
      notifications, and Web-based and print versions of the app would be extremely
      useful to mitigate some of their concerns. CONCLUSIONS: This study provided
      insight into the perspectives of LGBTQ+ YYA on a smoking cessation intervention
      delivered through a mobile app. The findings suggested a number of components of
      a mobile app that were valued and those that were concerning, as well as
      suggestions on how to make a mobile app cessation program successful. App
      development for this subpopulation should take into consideration the opinions of
      the intended users and involve them in the development and evaluation of mobile
      based smoking cessation programs.

PMID- 27864166
TI  - Perivascular Adipose Tissue Inflammation and Coronary Artery Disease: An Autopsy
      Study Protocol.
AB  - BACKGROUND: Perivascular adipose tissue (PAT) inflammation may have a role in
      coronary artery disease (CAD) pathophysiology. However, most evidence has come
      from samples obtained during surgical procedures that may imply in some
      limitations. Moreover, the role of B lymphocytes and inflammation in PAT that is
      adjacent to unstable atheroma plaques has not been investigated in humans using
      morphometric measurements. OBJECTIVE: The objective of this study is to
      investigate the inflammation in PAT, subcutaneous, and perirenal adipose tissues
      (SAT and PrAT) among chronic CAD, acute CAD, and control groups in an autopsy
      study. METHODS: Heart, SAT, and PrAT samples are collected from autopsied
      subjects in a general autopsy service, with the written informed consent of the
      next-of-kin (NOK). Sociodemographic and clinical data are obtained from a
      semistructure interview with the NOK. Coronary arteries are dissected and PAT are
      removed. Sections with the greatest arterial obstruction or unstable plaques, and
      the local with absence of atherosclerosis in all coronary arteries are sampled.
      PAT are represented adjacent to these fragments. Adipose tissues are fixed in 4%
      buffered paraformaldehyde solution and analyzed immunohistochemically for
      macrophages (CD68), macrophage polarization (CD11c for proinflammatory and CD206
      for anti-inflammatory), B lymphocytes (CD20), and T lymphocytes (CD3). Slides
      will be scanned, and inflammatory cells will be quantified in 20 random fields.
      Participants will be categorized in CAD groups, after morphometric measurement of
      arterial obstruction and plaque composition analysis in accordance with American
      Heart Association classification. Three study groups will be investigated: acute
      CAD (at least one unstable plaque); chronic CAD (>=50% arterial obstruction); and
      controls (<50% arterial obstruction). Inflammatory cells in PAT, SAT, and PrAT
      will be counted and compared between groups using multivariate linear regression,
      adjusted for age, body mass index, hypertension, diabetes, alcohol use, and
      smoking. RESULTS: We present the methods of our study that was developed from 2
      pilots. Currently, data collection and tissue processing are ongoing. Data
      collection, histology and immunochemistry procedures, and quantification of all
      inflammatory cells are expected to be concluded within 1 year. CONCLUSIONS: This
      study will contribute for the understanding of the mechanisms of CAD
      pathophysiology because it will help to clarify the role of inflammation both in
      chronic and acute CAD.

PMID- 27864167
TI  - Testing the Feasibility of Remote Patient Monitoring in Prenatal Care Using a
      Mobile App and Connected Devices: A Prospective Observational Trial.
AB  - BACKGROUND: Excessive weight gain and elevated blood pressure are significant
      risk factors for adverse pregnancy outcomes such as gestational diabetes,
      premature birth, and preeclampsia. More effective strategies to facilitate
      adherence to gestational weight gain goals and monitor blood pressure may have a
      positive health benefit for pregnant women and their babies. The impact of
      utilizing a remote patient monitoring system to monitor blood pressure and weight
      gain as a component of prenatal care has not been previously assessed. OBJECTIVE:
      The objective of this study is to determine the feasibility of monitoring
      patients remotely in prenatal care using a mobile phone app and connected digital
      devices. METHODS: In this prospective observational study, 8 women with low risk
      pregnancy in the first trimester were recruited at an urban academic medical
      center. Participants received a mobile phone app with a connected digital weight
      scale and blood pressure cuff for at-home data collection for the duration of
      pregnancy. At-home data was assessed for abnormal values of blood pressure or
      weight to generate clinical alerts to the patient and provider. As measures of
      the feasibility of the system, participants were studied for engagement with the
      app, accuracy of remote data, efficacy of alert system, and patient satisfaction.
      RESULTS: Patient engagement with the mobile app averaged 5.5 times per week over
      the 6-month study period. Weight data collection and blood pressure data
      collection averaged 1.5 times and 1.1 times per week, respectively. At-home
      measurements of weight and blood pressure were highly accurate compared to in
      office measurements. Automatic clinical alerts identified two episodes of
      abnormal weight gain with no false triggers. Patients demonstrated high
      satisfaction with the system. CONCLUSIONS: In this pilot study, we demonstrated
      that a system using a mobile phone app coupled to remote monitoring devices is
      feasible for prenatal care.

PMID- 27864165
TI  - Text to Move: A Randomized Controlled Trial of a Text-Messaging Program to
      Improve Physical Activity Behaviors in Patients With Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Text messages are increasingly being used because of the low cost and
      the ubiquitous nature of mobile phones to engage patients in self-care behaviors.
      Self-care is particularly important in achieving treatment outcomes in type 2
      diabetes mellitus (T2DM). OBJECTIVE: This study examined the effect of
      personalized text messages on physical activity, as measured by a pedometer, and
      clinical outcomes in a diverse population of patients with T2DM. METHODS: Text to
      Move (TTM) incorporates physical activity monitoring and coaching to provide
      automated and personalized text messages to help patients with T2DM achieve their
      physical activity goals. A total of 126 English- or Spanish-speaking patients
      with glycated hemoglobin A1c (HbA1c) >7 were enrolled in-person to participate in
      the study for 6 months and were randomized into either the intervention arm that
      received the full complement of the intervention or a control arm that received
      only pedometers. The primary outcome was change in physical activity. We also
      assessed the effect of the intervention on HbA1c, weight, and participant
      engagement. RESULTS: All participants (intervention: n=64; control: n=62) were
      included in the analyses. The intervention group had significantly higher monthly
      step counts in the third (risk ratio [RR] 4.89, 95% CI 1.20 to 19.92, P=.03) and
      fourth (RR 6.88, 95% CI 1.21 to 39.00, P=.03) months of the study compared to the
      control group. However, over the 6-month follow-up period, monthly step counts
      did not differ statistically by group (intervention group: 9092 steps; control
      group: 3722 steps; RR 2.44, 95% CI 0.68 to 8.74, P=.17). HbA1c decreased by 0.07%
      (95% CI -0.47 to 0.34, P=.75) in the TTM group compared to the control group.
      Within groups, HbA1c decreased significantly from baseline in the TTM group by 
      0.43% (95% CI -0.75 to -0.12, P=.01), but nonsignificantly in the control group
      by -0.21% (95% CI -0.49 to 0.06, P=.13). Similar changes were observed for other
      secondary outcomes. CONCLUSION: Personalized text messaging can be used to
      improve outcomes in patients with T2DM by employing optimal patient engagement
      measures.

PMID- 27864168
TI  - Biogeography of Oenococcus oeni Reveals Distinctive but Nonspecific Populations
      in Wine-Producing Regions.
AB  - : Understanding the mechanisms behind the typicity of regional wines inevitably
      brings attention to microorganisms associated with their production. Oenococcus
      oeni is the main bacterial species involved in wine and cider making. It develops
      after the yeast-driven alcoholic fermentation and performs the malolactic
      fermentation, which improves the taste and aromatic complexity of most wines.
      Here, we have evaluated the diversity and specificity of O. oeni strains in six
      regions. A total of 235 wines and ciders were collected during spontaneous
      malolactic fermentations and used to isolate 3,212 bacterial colonies. They were
      typed by multilocus variable analysis, which disclosed a total of 514 O. oeni
      strains. Their phylogenetic relationships were evaluated by a second typing
      method based on single nucleotide polymorphism (SNP) analysis. Taken together,
      the results indicate that each region holds a high diversity of strains that
      constitute a unique population. However, strains present in each region belong to
      diverse phylogenetic groups, and the same groups can be detected in different
      regions, indicating that strains are not genetically adapted to regions. In
      contrast, greater strain identity was seen for cider, white wine, or red wine of
      Burgundy, suggesting that genetic adaptation to these products occurred.
      IMPORTANCE: This study reports the isolation, genotyping, and geographic
      distribution analysis of the largest collection of O. oeni strains performed to
      date. It reveals that there is very high diversity of strains in each region, the
      majority of them being detected in a single region. The study also reports the
      development of an SNP genotyping method that is useful for analyzing the
      distribution of O. oeni phylogroups. The results show that strains are not
      genetically adapted to regions but to specific types of wines. They reveal new
      phylogroups of strains, particularly two phylogroups associated with white wines
      and red wines of Burgundy. Taken together, the results shed light on the
      diversity and specificity of wild strains of O. oeni, which is crucial for
      understanding their real contribution to the unique properties of wines.

PMID- 27864169
TI  - Increasing the Thermostable Sugar-1-Phosphate Nucleotidylyltransferase Activities
      of the Archaeal ST0452 Protein through Site Saturation Mutagenesis of the 97th
      Amino Acid Position.
AB  - : The ST0452 protein is a bifunctional protein exhibiting sugar-1-phosphate
      nucleotidylyltransferase (sugar-1-P NTase) and amino-sugar-1-phosphate
      acetyltransferase activities and was isolated from the thermophilic archaeon
      Sulfolobus tokodaii Based on the previous observation that five single mutations
      increased ST0452 sugar-1-P NTase activity, nine double-mutant ST0452 proteins
      were generated with the intent of obtaining enzymes exhibiting a further increase
      in catalysis, but all showed less than 15% of the wild-type N-acetyl-d
      glucosamine-1-phosphate uridyltransferase (GlcNAc-1-P UTase) activity. The Y97A
      mutant exhibited the highest activity of the single-mutant proteins, and thus
      site saturation mutagenesis of the 97th position (Tyr) was conducted. Six mutants
      showed both increased GlcNAc-1-P UTase and glucose-1-phosphate uridyltransferase
      activities, eight mutants showed only enhanced GlcNAc-1-P UTase activity, and six
      exhibited higher GlcNAc-1-P UTase activity than that of the Y97A mutant. Kinetic
      analyses of three typical mutants indicated that the increase in sugar-1-P NTase
      activity was mainly due to an increase in the apparent kcat value. We
      hypothesized that changing the 97th position (Tyr) to a smaller amino acid with
      similar electronic properties would increase activity, and thus the Tyr at the
      corresponding 103rd position of the Escherichia coli GlmU (EcGlmU) enzyme was
      replaced with the same residues. The Y103N mutant EcGlmU showed increased GlcNAc
      1-P UTase activity, revealing that the Tyr at the 97th position of the ST0452
      protein (103rd position in EcGlmU) plays an important role in catalysis. The
      present results provide useful information regarding how to improve the activity
      of natural enzymes and how to generate powerful enzymes for the industrial
      production of sugar nucleotides. IMPORTANCE: It is typically difficult to
      increase enzymatic activity by introducing substitutions into a natural enzyme.
      However, it was previously found that the ST0452 protein, a thermostable enzyme
      from the thermophilic archaeon Sulfolobus tokodaii, exhibited increased activity
      following single amino acid substitutions of Ala. In this study, ST0452 proteins
      exhibiting a further increase in activity were created using a site saturation
      mutagenesis strategy at the 97th position. Kinetic analyses showed that the
      increased activities of the mutant proteins were principally due to increased
      apparent kcat values. These mutant proteins might suggest clues regarding the
      mechanism underlying the reaction process and provide very important information
      for the design of synthetic improved enzymes, and they can be used as powerful
      biocatalysts for the production of sugar nucleotide molecules. Moreover, this
      work generated useful proteins for three-dimensional structural analysis
      clarifying the processes underlying the regulation and mechanism of enzymatic
      activity.

PMID- 27864170
TI  - Control of Biofilm Formation: Antibiotics and Beyond.
AB  - Biofilm-associated bacteria are less sensitive to antibiotics than free-living
      (planktonic) cells. Furthermore, with variations in the concentration of
      antibiotics throughout a biofilm, microbial cells are often exposed to levels
      below inhibitory concentrations and may develop resistance. This, as well as the
      irresponsible use of antibiotics, leads to the selection of pathogens that are
      difficult to eradicate. The Centers for Disease Control and Prevention use the
      terms "antibiotic" and "antimicrobial agent" interchangeably. However, a clear
      distinction between these two terms is required for the purpose of this
      assessment. Therefore, we define "antibiotics" as pharmaceutically formulated and
      medically administered substances and "antimicrobials" as a broad category of
      substances which are not regulated as drugs. This comprehensive minireview
      evaluates the effect of natural antimicrobials on pathogens in biofilms when used
      instead of, or in combination with, commonly prescribed antibiotics.

PMID- 27864171
TI  - Mitochondrial Superoxide Dismutase and Yap1p Act as a Signaling Module
      Contributing to Ethanol Tolerance of the Yeast Saccharomyces cerevisiae.
AB  - : There are two superoxide dismutases in the yeast Saccharomyces cerevisiae
      cytoplasmic and mitochondrial enzymes. Inactivation of the cytoplasmic enzyme,
      Sod1p, renders the cells sensitive to a variety of stresses, while inactivation
      of the mitochondrial isoform, Sod2p, typically has a weaker effect. One exception
      is ethanol-induced stress. Here we studied the role of Sod2p in ethanol tolerance
      of yeast. First, we found that repression of SOD2 prevents ethanol-induced
      relocalization of yeast hydrogen peroxide-sensing transcription factor Yap1p, one
      of the key stress resistance proteins. In agreement with this, the levels of
      Trx2p and Gsh1p, proteins encoded by Yap1 target genes, were decreased in the
      absence of Sod2p. Analysis of the ethanol sensitivities of the cells lacking
      Sod2p, Yap1p, or both indicated that the two proteins act in the same pathway.
      Moreover, preconditioning with hydrogen peroxide restored the ethanol resistance
      of yeast cells with repressed SOD2 Interestingly, we found that mitochondrion-to
      nucleus signaling by Rtg proteins antagonizes Yap1p activation. Together, our
      data suggest that hydrogen peroxide produced by Sod2p activates Yap1p and thus
      plays a signaling role in ethanol tolerance. IMPORTANCE: Baker's yeast harbors
      multiple systems that ensure tolerance to high concentrations of ethanol. Still,
      the role of mitochondria under severe ethanol stress in yeast is not completely
      clear. Our study revealed a signaling function of mitochondria which contributes
      significantly to the ethanol tolerance of yeast cells. We found that
      mitochondrial superoxide dismutase Sod2p and cytoplasmic hydrogen peroxide sensor
      Yap1p act together as a module of the mitochondrion-to-nucleus signaling pathway.
      We also report cross talk between this pathway and the conventional retrograde
      signaling cascade activated by dysfunctional mitochondria.

PMID- 27864172
TI  - The EbpA-RpoN Regulatory Pathway of the Pathogen Leptospira interrogans Is
      Essential for Survival in the Environment.
AB  - Leptospira interrogans is the agent of leptospirosis, a reemerging zoonotic
      disease. It is transmitted to humans through environmental surface waters
      contaminated by the urine of mammals chronically infected by pathogenic strains
      able to survive in water for long periods. Little is known about the regulatory
      pathways underlying environmental sensing and host adaptation of L. interrogans
      during its enzootic cycle. This study identifies the EbpA-RpoN regulatory pathway
      in L. interrogans In this pathway, EbpA, a sigma54 activator and putative
      prokaryotic enhancer-binding protein (EBP), and the alternative sigma factor RpoN
      (sigma54) control expression of at least three genes, encoding AmtB (an ammonium
      transport protein) and two proteins of unknown function. Electrophoresis mobility
      shift assay demonstrated that recombinant RpoN and EbpA bind to the promoter
      region and upstream of these three identified genes, respectively. Genetic
      disruption of ebpA in L. interrogans serovar Manilae virtually abolished
      expression of the three genes, including amtB in two independent ebpA mutants.
      Complementation of the ebpA mutant restored expression of these genes.
      Intraperitoneal inoculation of gerbils with the ebpA mutant did not affect
      mortality. However, the ebpA mutant had decreased cell length in vitro and had a
      significantly lowered cell density at stationary phase when grown with l-alanine
      as the sole nitrogen source. Furthermore, the ebpA mutant has dramatically
      reduced long-term survival ability in water. Together, these studies identify a
      regulatory pathway, the EbpA-RpoN pathway, that plays an important role in the
      zoonotic cycle of L. interrogans IMPORTANCE: Leptospirosis is a reemerging
      disease with global importance. However, our understanding of gene regulation of
      the spirochetal pathogen Leptospira interrogans is still in its infancy, largely
      due to the lack of robust tools for genetic manipulation of this spirochete.
      Little is known about how the pathogen achieves its long-term survival in the
      aquatic environment. By utilizing bioinformatic, genetic, and biochemical
      methods, we discovered a regulatory pathway in L. interrogans, the EbpA-RpoN
      pathway, and demonstrated that this pathway plays an important role in
      environmental survival of this pathogen.

PMID- 27864173
TI  - Salad Leaf Juices Enhance Salmonella Growth, Colonization of Fresh Produce, and
      Virulence.
AB  - : We show in this report that traces of juices released from salad leaves as they
      become damaged can significantly enhance colonization of salad leaves by
      Salmonella enterica Salad juices in water increased Salmonella growth by 110%
      over the level seen with the unsupplemented control and in host-like serum-based
      media by more than 2,400-fold over control levels. In serum-based media, salad
      juices induced growth of Salmonella via provision of Fe from transferrin, and
      siderophore production was found to be integral to the growth induction process.
      Other aspects relevant to salad leaf colonization and retention were enhanced,
      such as motility and biofilm formation, which were increased over control levels
      by >220% and 250%, respectively; direct attachment to salad leaves increased by
      >350% when a salad leaf juice was present. In terms of growth and biofilm
      formation, the endogenous salad leaf microbiota was largely unresponsive to leaf
      juice, suggesting that Salmonella gains a marked growth advantage from fluids
      released by salad leaf damage. Salad leaf juices also enhanced pathogen
      attachment to the salad bag plastic. Over 5 days of refrigeration (a typical
      storage time for bagged salad leaves), even traces of juice within the salad bag
      fluids increased Salmonella growth in water by up to 280-fold over control
      cultures, as well as enhancing salad bag colonization, which could be an
      unappreciated factor in retention of pathogens in fresh produce. Collectively,
      the study data show that exposure to salad leaf juice may contribute to the
      persistence of Salmonella on salad leaves and strongly emphasize the importance
      of ensuring the microbiological safety of fresh produce. IMPORTANCE: Salad leaves
      are an important part of a healthy diet but have been associated in recent years
      with a growing risk of food poisoning from bacterial pathogens such as Salmonella
      enterica Although this is considered a significant public health problem, very
      little is known about the behavior of Salmonella in the actual salad bag. We show
      that juices released from the cut ends of the salad leaves enabled the Salmonella
      cells to grow in water, even when it was refrigerated. Salad juice exposure also
      helped the Salmonella cells to attach to the salad leaves so strongly that
      washing could not remove them. Collectively, the results presented in this report
      show that exposure to even traces of salad leaf juice may contribute to the
      persistence of Salmonella on salad leaves as well as priming it for establishing
      an infection in the consumer.

PMID- 27864175
TI  - The Acceptor Side of Photosystem II Is the Initial Target of Nitrite Stress in
      Synechocystis sp. Strain PCC 6803.
AB  - Nitrite, a common form of inorganic nitrogen (N), can be used as a nitrogen
      source through N assimilation. However, high levels of nitrite depress
      photosynthesis in various organisms. In this study, we investigated which
      components of the photosynthetic electron transfer chain are targeted by nitrite
      stress in Synechocystis sp. strain PCC 6803 cells. Measurements of whole-chain
      and photosystem II (PSII)-mediated electron transport activities revealed that
      high levels of nitrite primarily impair electron flow in PSII. Changes in PSII
      activity in response to nitrite stress occurred in two distinct phases. During
      the first phase, which occurred in the first 3 h of nitrite treatment, electron
      transfer from the primary quinone acceptor (QA) to the secondary quinone acceptor
      (QB) was retarded, as indicated by chlorophyll (Chl) a fluorescence induction, S
      state distribution, and QA- reoxidation tests. In the second phase, which
      occurred after 6 h of nitrite exposure, the reaction center was inactivated and
      the donor side of photosystem II was inhibited, as revealed by changes in Chl
      fluorescence parameters and thermoluminescence and by immunoblot analysis. Our
      data suggest that nitrite stress is highly damaging to PSII and disrupts PSII
      activity by a stepwise mechanism in which the acceptor side is the initial
      target. IMPORTANCE In our previous studies, an alga-based technology was proposed
      to fix the large amounts of nitrite that are released from NOX-rich flue gases
      and proved to be a promising industrial strategy for flue gas NOX bioremediation
      (W. Chen et al., Environ Sci Technol 50:1620-1627, 2016,
      https://doi.org/10.1021/acs.est.5b04696; X. Zhang et al., Environ Sci Technol
      48:10497-10504, 2014, https://doi.org/10.1021/es5013824). However, the toxic
      effects of high concentrations of nitrite on algal cells remain obscure. The
      analysis of growth rates, photochemistry, and protein profiles in our study
      provides important evidence that the inhibition by nitrite occurs in two phases:
      in the first phase, electron transfer between QA- and QB is retarded, whereas in
      the second, the donor side of PSII is affected. This is an excellent example of
      investigating the "early" inhibitory effects (i.e., within the first 6 h) on the
      PSII electron transfer chain in vivo This paper provides novel insights into the
      mechanisms of nitrite inhibition of photosynthesis in an oxygenic phototrophic
      cyanobacterium.

PMID- 27864174
TI  - Multilocus Sequence Analysis of Phylogroup 1 and 2 Oral Treponeme Strains.
AB  - : More than 75 "species-level" phylotypes of spirochete bacteria belonging to the
      genus Treponema reside within the human oral cavity. The majority of these oral
      treponeme phylotypes correspond to as-yet-uncultivated taxa or strains of
      uncertain standing in taxonomy. Here, we analyze phylogenetic and taxonomic
      relationships between oral treponeme strains using a multilocus sequence analysis
      (MLSA) scheme based on the highly conserved 16S rRNA, pyrH, recA, and flaA genes.
      We utilized this MLSA scheme to analyze genetic data from a curated collection of
      oral treponeme strains (n = 71) of diverse geographical origins. This comprises
      phylogroup 1 (n = 23) and phylogroup 2 (n = 48) treponeme strains, including all
      relevant American Type Culture Collection reference strains. The taxonomy of all
      strains was confirmed or inferred via the analysis of ca. 1,450-bp 16S rRNA gene
      sequences using a combination of bioinformatic and phylogenetic approaches.
      Taxonomic and phylogenetic relationships between the respective treponeme strains
      were further investigated by analyzing individual and concatenated flaA (1,074
      nucleotide [nt]), recA (1,377-nt), and pyrH (696-nt) gene sequence data sets. Our
      data confirmed the species differentiation between Treponema denticola (n = 41)
      and Treponema putidum (n = 7) strains. Notably, our results clearly supported the
      differentiation of the 23 phylogroup 1 treponeme strains into five distinct
      "species-level" phylotypes. These respectively corresponded to "Treponema
      vincentii" (n = 11), Treponema medium (n = 1), "Treponema sinensis" (Treponema
      sp. IA; n = 4), Treponema sp. IB (n = 3), and Treponema sp. IC (n = 4). In
      conclusion, our MLSA-based approach can be used to effectively discriminate oral
      treponeme taxa, confirm taxonomic assignment, and enable the delineation of
      species boundaries with high confidence. IMPORTANCE: Periodontal diseases are
      caused by persistent polymicrobial biofilm infections of the gums and underlying
      tooth-supporting structures and have a complex and variable etiology. Although
      Treponema denticola is strongly associated with periodontal diseases, the
      etiological roles of other treponeme species/phylotypes are less well defined.
      This is due to a paucity of formal species descriptions and a poor understanding
      of genetic relationships between oral treponeme taxa. Our study directly
      addresses these issues. It represents one of the most comprehensive analyses of
      oral treponeme strains performed to date, including isolates from North America,
      Europe, and Asia. We envisage that our results will greatly facilitate future
      metagenomic efforts aimed at characterizing the clinical distributions of oral
      treponeme species/phylotypes, helping investigators to establish a more detailed
      understanding of their etiological roles in periodontal diseases and other
      infectious diseases. Our results are also directly relevant to various
      polymicrobial tissue infections in animals, which also involve treponeme
      populations.

PMID- 27864176
TI  - Insights into the Biosynthesis of Duramycin.
AB  - : Lantibiotics are ribosomally synthesized and posttranslationally modified
      antimicrobial peptides that are characterized by the thioether cross-linked
      bisamino acids lanthionine (Lan) and methyllanthionine (MeLan). Duramycin
      contains 19 amino acids, including one Lan and two MeLans, an unusual
      lysinoalanine (Lal) bridge formed from the epsilon-amino group of lysine 19 and a
      serine residue at position 6, and an erythro-3-hydroxy-l-aspartic acid at
      position 15. These modifications are important for the interactions of duramycin
      with its biological target, phosphatidylethanolamine (PE). Based on the binding
      affinity and specificity for PE, duramycin has been investigated as a potential
      therapeutic, as a molecular probe to investigate the role and localization of PE
      in biological systems, and to block viral entry into mammalian cells. In this
      study, we identified the duramycin biosynthetic gene cluster by genome sequencing
      of Streptomyces cinnamoneus ATCC 12686 and investigated the dur biosynthetic
      machinery by heterologous expression in Escherichia coli In addition, the analog
      duramycin C, containing six amino acid changes compared to duramycin, was
      successfully generated in E. coli The substrate recognition motif of DurX, an
      alpha-ketoglutarate/iron(II)-dependent hydroxylase that carries out the
      hydroxylation of aspartate 15 of the precursor peptide DurA, was also
      investigated using mutagenesis of the DurA peptide. Both in vivo and in vitro
      results demonstrated that Gly16 is important for DurX activity. IMPORTANCE:
      Duramycin is a natural product produced by certain bacteria that binds to
      phosphatidylethanolamine (PE). Because PE is involved in many cellular processes,
      duramycin is an antibiotic that kills bacteria, but it has also been used as a
      molecular probe to detect PE and monitor its localization in mammalian cells and
      even whole organisms, and it was recently shown to display broad-spectrum
      inhibition of viral entry into host cells. In addition, the molecule has been
      evaluated as treatment for cystic fibrosis. We report here the genes that are
      involved in duramycin biosynthesis, and we produced duramycin by expressing those
      genes in Escherichia coli We show that duramycin analogs can also be produced.
      The ability to access duramycin and analogs by production in E. coli opens
      opportunities to improve duramycin as an antibiotic, PE probe, antiviral, or
      cystic fibrosis therapeutic.

PMID- 27864177
TI  - Histone Deacetylase HDA-2 Regulates Trichoderma atroviride Growth, Conidiation,
      Blue Light Perception, and Oxidative Stress Responses.
AB  - : Fungal blue-light photoreceptors have been proposed as integrators of light and
      oxidative stress. However, additional elements participating in the integrative
      pathway remain to be identified. In Trichoderma atroviride, the blue-light
      regulator (BLR) proteins BLR-1 and -2 are known to regulate gene transcription,
      mycelial growth, and asexual development upon illumination, and recent global
      transcriptional analysis revealed that the histone deacetylase-encoding gene hda
      2 is induced by light. Here, by assessing responses to stimuli in wild-type and
      Deltahda-2 backgrounds, we evaluate the role of HDA-2 in the regulation of genes
      responsive to light and oxidative stress. Deltahda-2 strains present reduced
      growth, misregulation of the con-1 gene, and absence of conidia in response to
      light and mechanical injury. We found that the expression of hda-2 is BLR-1
      dependent and HDA-2 in turn is essential for the transcription of early and late
      light-responsive genes that include blr-1, indicating a regulatory feedback loop.
      When subjected to reactive oxygen species (ROS), Deltahda-2 mutants display high
      sensitivity whereas Deltablr strains exhibit the opposite phenotype.
      Consistently, in the presence of ROS, ROS-related genes show high transcription
      levels in wild-type and Deltablr strains but misregulation in Deltahda-2 mutants.
      Finally, chromatin immunoprecipitations of histone H3 acetylated at Lys9/Lys14 on
      cat-3 and gst-1 promoters display low accumulation of H3K9K14ac in Deltablr and
      Deltahda-2 strains, suggesting indirect regulation of ROS-related genes by HDA-2.
      Our results point to a mutual dependence between HDA-2 and BLR proteins and
      reveal the role of these proteins in an intricate gene regulation landscape in
      response to blue light and ROS. IMPORTANCE: Trichoderma atroviride is a free
      living fungus commonly found in soil or colonizing plant roots and is widely used
      as an agent in biocontrol as it parasitizes other fungi, stimulates plant growth,
      and induces the plant defense system. To survive in various environments, fungi
      constantly sense and respond to potentially threatening external factors, such as
      light. In particular, UV light can damage biomolecules by producing free-radical
      reactions, in most cases involving reactive oxygen species (ROS). In T.
      atroviride, conidiation is essential for its survival, which is induced by light
      and mechanical injury. Notably, conidia are typically used as the inoculum in the
      field during biocontrol. Therefore, understanding the linkages between responses
      to light and exposure to ROS in T. atroviride is of major basic and practical
      relevance. Here, the histone deacetylase-encoding gene hda-2 is induced by light
      and ROS, and its product regulates growth, conidiation, blue light perception,
      and oxidative stress responses.

PMID- 27864180
TI  - Alison Mary Bangham.

PMID- 27864179
TI  - Prevalence of Antibiotic Resistance Genes among Human Gut-Derived Bifidobacteria.
AB  - : The microbiota of the human gastrointestinal tract (GIT) may regularly be
      exposed to antibiotics, which are used to prevent and treat infectious diseases
      caused by bacteria and fungi. Bacterial communities of the gut retain a reservoir
      of antibiotic resistance (AR) genes, and antibiotic therapy thus positively
      selects for those microorganisms that harbor such genetic features, causing
      microbiota modulation. During the first months following birth, bifidobacteria
      represent some of the most dominant components of the human gut microbiota,
      although little is known about their AR gene complement (or resistome). In the
      current study, we assessed the resistome of the Bifidobacterium genus based on
      phenotypic and genotypic data of members that represent all currently recognized
      bifidobacterial (sub)species. Moreover, a comparison between the bifidobacterial
      resistome and gut metagenome data sets from adults and infants shows that the
      bifidobacterial community present at the first week following birth possesses a
      reduced AR arsenal compared to that present in the infant bifidobacterial
      population in subsequent weeks of the first year of life. Our findings reinforce
      the concept that the early infant gut microbiota is more susceptible to
      disturbances by antibiotic treatment than the gut microbiota developed at a later
      life stage. IMPORTANCE: The spread of resistance to antibiotics among bacterial
      communities has represented a major concern since their discovery in the last
      century. The risk of genetic transfer of resistance genes between microorganisms
      has been extensively investigated due to its relevance to human health. In
      contrast, there is only limited information available on antibiotic resistance
      among human gut commensal microorganisms such as bifidobacteria, which are widely
      exploited by the food industry as health-promoting microorganisms or probiotic
      ingredients. In the current study, we explored the occurrence of antibiotic
      resistance genes in the genomes of bifidobacteria and evaluated their genetic
      mobility to other human gut commensal microorganisms.

PMID- 27864181
TI  - David Davin.

PMID- 27864178
TI  - Microbial Nursery Production of High-Quality Biological Soil Crust Biomass for
      Restoration of Degraded Dryland Soils.
AB  - Biological soil crusts (biocrusts) are slow-growing, phototroph-based microbial
      assemblages that develop on the topsoils of drylands. Biocrusts help maintain
      soil fertility and reduce erosion. Because their loss through human activities
      has negative ecological and environmental health consequences, biocrust
      restoration is of interest. Active soil inoculation with biocrust microorganisms
      can be an important tool in this endeavor. We present a culture-independent, two
      step process to grow multispecies biocrusts in open greenhouse nursery
      facilities, based on the inoculation of local soils with local biocrust remnants
      and incubation under seminatural conditions that maintain the essence of the
      habitat but lessen its harshness. In each of four U.S. Southwest sites, we tested
      and deployed combinations of factors that maximized growth (gauged as chlorophyll
      a content) while minimizing microbial community shifts (assessed by 16S rRNA
      sequencing and bioinformatics), particularly for crust-forming cyanobacteria.
      Generally, doubling the frequency of natural wetting events, a 60% reduction in
      sunlight, and inoculation by slurry were optimal. Nutrient addition effects were
      site specific. In 4 months, our approach yielded crusts of high inoculum quality
      reared on local soil exposed to locally matched climates, acclimated to
      desiccation, and containing communities minimally shifted in composition from
      local ones. Our inoculum contained abundant crust-forming cyanobacteria and no
      significant numbers of allochthonous phototrophs, and it was sufficient to treat
      ca. 6,000 m2 of degraded dryland soils at 1 to 5% of the typical crust biomass
      concentration, having started from a natural crust remnant as small as 6 to 30
      cm2 IMPORTANCE: Soil surface crusts can protect dryland soils from erosion, but
      they are often negatively impacted by human activities. Their degradation causes
      a loss of fertility, increased production of fugitive dust and intensity of dust
      storms with associated traffic problems, and provokes general public health
      hazards. Our results constitute an advance in the quest to actively restore
      biological soil covers by providing a means to obtain high-quality inoculum
      within a reasonable time (a few months), thereby allowing land managers to
      recover essential, but damaged, ecosystem services in a sustainable, self
      perpetuating way as provided by biocrust communities.

PMID- 27864182
TI  - Pleuromediastinal Epithelial-Myoepithelial Carcinomas: A Clinicopathologic and
      Immunohistochemical Study of Two Cases.
AB  - OBJECTIVES: Two cases of epithelial-myoepithelial carcinoma are presented, one
      arising in the pleura and the other in the anterior mediastinum. The cases
      represent a unique distribution of these tumors within the thoracic cavity.
      METHODS: Both patients were men aged 25 and 68 years, respectively, who had chest
      pain and dyspnea. Imaging revealed an anterior mediastinal mass in one patient
      and a pleural-based tumor in the other. Neither patient had any history of
      malignancy, and physical examination did not disclose any tumor elsewhere.
      RESULTS: Initial biopsy specimens were inconclusive, and final diagnosis was
      deferred to surgical resection performed via median sternotomy and thoracotomy,
      respectively. Histologically, the lesions were characterized by epithelial and
      myoepithelial elements distributed as discrete tubules or duct-like structures or
      sheets of neoplastic cells. Immunohistochemistry showed positive staining for
      cytokeratin and epithelial membrane antigen in the epithelial component, while
      S100 protein and smooth muscle actin were expressed in the myoepithelial
      elements. Follow-up showed that both patients were alive 6 and 12 months after
      surgery, respectively. CONCLUSIONS: These cases highlight the ubiquitous
      distribution of salivary gland-type tumors in the thoracic cavity. These tumors
      should be included in the differential diagnosis of thoracic neoplasms also in
      locations other than the lung.

PMID- 27864183
TI  - County-Level Variation in Cardiovascular Disease Mortality in the United States
      in 2009-2013: Comparative Assessment of Contributing Factors.
AB  - We examined factors responsible for variation in cardiovascular disease (CVD)
      mortality across US counties in 2009-2013. We linked county-level census, survey,
      administrative, and vital statistics data to examine 4 sets of features:
      demographic factors, social and economic factors, health-care utilization and
      features of the environment, and population health indicators. County-level
      associations of these features (standardized to a mean of 0 with a standard
      deviation of 1) with cardiovascular deaths per 100,000 person-years among adults
      aged 45-74 years was modeled using 2-level hierarchical linear regression with
      random intercept for state. The percentage of CVD mortality variation
      (intercounty disparity) modeled by each set of features was quantified.
      Demographic composition accounted for 36% of county CVD mortality variation, and
      another 32% was explained after inclusion of economic/social conditions. Health
      care utilization, features of the environment, and health indicators explained an
      additional 6% of CVD mortality variation. The largest contributors to CVD
      mortality levels were median income (-23.61 deaths/100,000 person-years, 95% CI: 
      26.95, -20.26) and percentage without a high school education (20.71
      deaths/100,000 person-years, 95% CI: 16.48, 24.94). In comparison, the largest
      health-related contributors were health-care utilization (19.35 deaths/100,000
      person-years, 95% CI: 16.36, 22.34) and CVD risk factors (4.80 deaths/100,000
      person-years, 95% CI: 2.14, 7.46). Improving health-care access and decreasing
      the prevalence of traditional CVD risk factors may reduce county CVD mortality
      levels, but improving socioeconomic circumstances of disadvantaged counties will
      be required in order to reduce CVD mortality disparities across counties.

PMID- 27864184
TI  - Surgical Versus Nonsurgical Treatment for Midshaft Clavicle Fractures in Patients
      Aged 16 Years and Older: A Systematic Review, Meta-analysis, and Comparison of
      Randomized Controlled Trials and Observational Studies.
AB  - BACKGROUND: There is no consensus on the choice of treatment of midshaft clavicle
      fractures (MCFs). PURPOSE: The aims of this systematic review and meta-analysis
      were (1) to compare fracture healing disorders and functional outcomes of
      surgical versus nonsurgical treatment of MCFs and (2) to compare effect estimates
      obtained from randomized controlled trials (RCTs) and observational studies.
      STUDY DESIGN: Systematic review and meta-analysis. METHODS: The PubMed/MEDLINE,
      Embase, CENTRAL, and CINAHL databases were searched for both RCTs and
      observational studies. Using the MINORS instrument, all included studies were
      assessed on their methodological quality. The primary outcome was a nonunion.
      Effects of surgical versus nonsurgical treatment were estimated using random
      effects meta-analysis models. RESULTS: A total of 20 studies were included, of
      which 8 were RCTs and 12 were observational studies including 1760 patients.
      Results were similar across the different study designs. A meta-analysis of 19
      studies revealed that nonunions were significantly less common after surgical
      treatment than after nonsurgical treatment (odds ratio [OR], 0.18 [95% CI, 0.10
      0.33]). The risk of malunions did not differ between surgical and nonsurgical
      treatment (OR, 0.38 [95% CI, 0.12-1.19]). Both the long-term Disabilities of the
      Arm, Shoulder and Hand (DASH) and Constant-Murley scores favored surgical
      treatment (DASH: mean difference [MD], -2.04 [95% CI, -3.56 to -0.52]; Constant
      Murley: MD, 3.23 [95% CI, 1.52 to 4.95]). No differences were observed regarding
      revision surgery (OR, 0.85 [95% CI, 0.42-1.73]). Including only high-quality
      studies, both the number of malunions and days to return to work show significant
      differences in favor of surgical treatment (malunions: OR, 0.26 [95% CI, 0.07 to
      0.92]; return to work: MD, -8.64 [95% CI, -16.22 to -1.05]). CONCLUSION: This
      meta-analysis of high-quality studies showed that surgical treatment of MCFs
      results in fewer nonunions, fewer malunions, and an accelerated return to work
      compared with nonsurgical treatment. A meta-analysis of surgical treatments need
      not be restricted to randomized trials, provided that the included observational
      studies are of high quality.

PMID- 27864185
TI  - The Pediatric International Knee Documentation Committee (Pedi-IKDC) Subjective
      Knee Evaluation Form: Normative Data.
AB  - BACKGROUND: Children are participating in sports at an increasingly younger age,
      which has contributed to an increased incidence of knee injuries among this
      population. Because of increased interest in the application of patient-reported
      outcome measures in orthopaedic surgery to evaluate treatment results, numerous
      knee outcome scores, including the International Knee Documentation Committee
      Subjective Form (IKDC), have been used to evaluate the knee. Although the IKDC
      has been validated only in adults, it is also being used for children because of
      a lack of appropriate outcome scores in the pediatric population. To address this
      concern, a pediatric version of the IKDC (Pedi-IKDC) was developed and evaluated
      for reliability, validity, and responsiveness. However, normative data for the
      Pedi-IKDC have not been established. PURPOSE: We aimed to aid the interpretation
      of Pedi-IKDC scores by characterizing normative data in children and adolescents
      and to validate the Pedi-IKDC by examining differences in scores among children
      who had a history of knee surgery or limited activity compared with those who did
      not. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: We
      conducted a cross-sectional survey of 2000 children and adolescents aged 10 to 18
      years living in the United States, who were recruited by ORC International to
      obtain equal numbers of participants by sex and by integer age group.
      Participants were asked to complete the Pedi-IKDC for 1 study-designated "index"
      knee (right or left) and to provide demographic data and information on their
      knee surgery history and recent (4-week) activity limitations. Raw Pedi-IKDC
      total scores were rescaled to a 0 to 100 scale. We used nonparametric Wilcoxon or
      Kruskal-Wallis tests to compare subgroup scores, and we used the van Elteren test
      to adjust for age. Unadjusted and adjusted P values were similar, and only
      unadjusted values are reported. RESULTS: The number of respondents (N = 2000) was
      uniform with respect to age and sex, with 11% in each age represented (10-18
      years). Fifty percent of respondents were female. Forty-nine states plus
      Washington, DC, were represented. In addition, 68% and 86% of respondents
      identified themselves as white and non-Hispanic, respectively. Seven percent of
      respondents (n = 136) respondents reported having prior surgery in 1 or both
      knees; 4% of these surgeries (n = 79) were in the index knee. The Pedi-IKDC score
      distribution was skewed left (mean +/- SD score, 86.7 +/- 16.8; median, 94.6) and
      34% of scores reached the ceiling value of 100. Participants who reported prior
      surgery or limited activity in the index knee had median Pedi-IKDC scores that
      were approximately 25 points lower than participants without these histories ( P
      < .0001 for both comparisons). In contrast, although it was statistically
      significant, the variation by age ( P = .02), race ( P = .02), ethnicity ( P =
      .01), and level of sports/exercise participation ( P = .04) was much smaller (all
      ranges of median scores <4.5). There were no significant differences in scores in
      terms of respondent sex or geographic region. CONCLUSION: Normative Pedi-IKDC
      scores were determined in this study. The strong association between Pedi-IKDC
      scores and prior knee surgery as well as recent activity limitations in the index
      knee can be used to evaluate clinical outcomes and supports the construct
      validity of the Pedi-IKDC. There was a large ceiling effect, with 34% of scores
      at the maximum value of 100. The lack of a sex-based effect and the minor
      variation with age both simplify the interpretation and use of the Pedi-IKDC.
      Therefore, Pedi-IKDC score distributions can provide assumptions for use in
      sample size or power calculations for research.

PMID- 27864187
TI  - Experts weigh minimum naloxone dose as opioid crisis evolves.

PMID- 27864188
TI  - FDA approves new naloxone strength.

PMID- 27864189
TI  - Hospital's team effort helps to save boy from deadly amoebic infection.

PMID- 27864186
TI  - Does Industry-Driven Alcohol Marketing Influence Adolescent Drinking Behaviour? A
      Systematic Review.
AB  - AIM: To systematically review evidence on the influence of specific marketing
      components (Price, Promotion, Product attributes and Place of sale/availability)
      on key drinking outcomes (initiation, continuation, frequency and intensity) in
      young people aged 9-17. METHODS: MEDLINE, EMBASE, SCOPUS, PsychINFO, CINAHL and
      ProQuest were searched from inception to July 2015, supplemented with searches of
      Google Scholar, hand searches of key journals and backward and forward citation
      searches of reference lists of identified papers. RESULTS: Forty-eight papers
      covering 35 unique studies met inclusion criteria. Authors tended to report that
      greater exposure to alcohol marketing impacted on drinking initiation,
      continuation, frequency and intensity during adolescence. Nevertheless, 23 (66%)
      studies reported null results or negative associations, often in combination with
      positive associations, resulting in mixed findings within and across studies.
      Heterogeneity in study design, content and outcomes prevented estimation of
      effect sizes or exploration of variation between countries or age subgroups. The
      strength of the evidence base differed according to type of marketing exposure
      and drinking outcome studied, with support for an association between alcohol
      promotion (mainly advertising) and drinking outcomes in adolescence, whilst only
      two studies examined the relationship between alcohol price and the drinking
      behaviour of those under the age of 18. CONCLUSION: Despite the volume of work,
      evidence is inconclusive in all four areas of marketing but strongest for
      promotional activity. Future research with standardized measures is needed to
      build on this work and better inform interventions and policy responses.

PMID- 27864192
TI  - California Medicaid to pay for five pharmacist services other than CMM.

PMID- 27864194
TI  - Bezlotoxumab approved to prevent Clostridium difficile recurrence.

PMID- 27864195
TI  - Summaries of safety labeling changes approved by FDA-boxed warnings highlights,
      July-September 2016.

PMID- 27864196
TI  - State affiliate initiative to advance ambulatory care practice.

PMID- 27864197
TI  - Documentation of clinical interventions by pharmacy students and recent pharmacy
      graduates.

PMID- 27864198
TI  - Problems with the current approach to residency research.

PMID- 27864199
TI  - Problems with the current approach to residency research.

PMID- 27864200
TI  - Implementation of chronic care management services in primary care practice.

PMID- 27864201
TI  - Precision medicine in oncology: New practice models and roles for oncology
      pharmacists.
AB  - PURPOSE: Three different precision medicine practice models developed by oncology
      pharmacists are described, including strategies for implementation and
      recommendations for educating the next generation of oncology pharmacy
      practitioners. SUMMARY: Oncology is unique in that somatic mutations can both
      drive the development of a tumor and serve as a therapeutic target for treating
      the cancer. Precision medicine practice models are a forum through which
      interprofessional teams, including pharmacists, discuss tumor somatic mutations
      to guide patient-specific treatment. The University of Wisconsin, Indiana
      University, and Moffit Cancer Center have implemented precision medicine practice
      models developed and led by oncology pharmacists. Different practice models,
      including a clinic, a clinical consultation service, and a molecular tumor board
      (MTB), were adopted to enhance integration into health systems and payment
      structures. Although the practice models vary, commonalities of three models
      include leadership by the clinical pharmacist, specific therapeutic
      recommendations, procurement of medications for off-label use, and a research
      component. These three practice models function as interprofessional training
      sites for pharmacy and medical students and residents, providing an important
      training resource at these institutions. Key implementation strategies include
      interprofessional involvement, institutional support, integration into clinical
      workflow, and selection of model by payer mix. CONCLUSION: MTBs are a pathway for
      clinical implementation of genomic medicine in oncology and are an emerging
      practice model for oncology pharmacists. Because pharmacists must be prepared to
      participate fully in contemporary practice, oncology pharmacy residents must be
      trained in genomic oncology, schools of pharmacy should expand precision medicine
      and genomics education, and opportunities for continuing education in precision
      medicine should be made available to practicing pharmacists.

PMID- 27864203
TI  - Implementation of a multidisciplinary pharmacogenomics clinic in a community
      health system.
AB  - PURPOSE: The development and implementation of a multidisciplinary
      pharmacogenomics clinic within the framework of an established community-based
      medical genetics program are described. SUMMARY: Pharmacogenomics is an important
      component of precision medicine that holds considerable promise for
      pharmacotherapy optimization. As part of the development of a health system-wide
      integrated pharmacogenomics program, in early 2015 Northshore University Health
      System established a pharmacogenomics clinic run by a multidisciplinary team
      including a medical geneticist, a pharmacist, a nurse practitioner, and genetic
      counselors. The team identified five key program elements: (1) a billable-service
      provider, (2) a process for documentation of relevant medication and family
      histories, (3) personnel with the knowledge required to interpret pharmacogenomic
      results, (4) personnel to discuss risks, benefits, and limitations of
      pharmacogenomic testing, and (5) a mechanism for reporting results. The most
      important program component is expert interpretation of genetic test results to
      provide clinically useful information; pharmacists are well positioned to provide
      that expertise. At the Northshore University HealthSystem pharmacogenomics
      clinic, patient encounters typically entail two one-hour visits and follow a
      standardized workflow. At the first visit, pharmacogenomics-focused medication
      and family histories are obtained, risks and benefits of genetic testing are
      explained, and a test sample is collected; at the second visit, test results are
      provided along with evidence-based pharmacotherapy recommendations. CONCLUSION: A
      multidisciplinary clinic providing genotyping and related services can facilitate
      the integration of pharmacogenomics into clinical care and meet the needs of
      early adopters of precision medicine.

PMID- 27864202
TI  - Implementation of inpatient models of pharmacogenetics programs.
AB  - PURPOSE: The operational elements essential for establishing an inpatient
      pharmacogenetic service are reviewed, and the role of the pharmacist in the
      provision of genotype-guided drug therapy in pharmacogenetics programs at three
      institutions is highlighted. SUMMARY: Pharmacists are well positioned to assume
      important roles in facilitating the clinical use of genetic information to
      optimize drug therapy given their expertise in clinical pharmacology and
      therapeutics. Pharmacists have assumed important roles in implementing inpatient
      pharmacogenetics programs. This includes programs designed to incorporate genetic
      test results to optimize antiplatelet drug selection after percutaneous coronary
      intervention and personalize warfarin dosing. Pharmacist involvement occurs on
      many levels, including championing and leading pharmacogenetics implementation
      efforts, establishing clinical processes to support genotype-guided therapy,
      assisting the clinical staff with interpreting genetic test results and applying
      them to prescribing decisions, and educating other healthcare providers and
      patients on genomic medicine. The three inpatient pharmacogenetics programs
      described use reactive versus preemptive genotyping, the most feasible approach
      under the current third-party payment structure. All three sites also follow
      Clinical Pharmacogenetics Implementation Consortium guidelines for drug therapy
      recommendations based on genetic test results. CONCLUSION: With the clinical
      emergence of pharmacogenetics into the inpatient setting, it is important that
      pharmacists caring for hospitalized patients are well prepared to serve as
      experts in interpreting and applying genetic test results to guide drug therapy
      decisions. Since genetic test results may not be available until after patient
      discharge, pharmacists practicing in the ambulatory care setting should also be
      prepared to assist with genotype-guided drug therapy as part of transitions in
      care.

PMID- 27864204
TI  - Integrating pharmacogenomics into electronic health records with clinical
      decision support.
AB  - PURPOSE: Existing pharmacogenomic informatics models, key implementation steps,
      and emerging resources to facilitate the development of pharmacogenomic clinical
      decision support (CDS) are described. SUMMARY: Pharmacogenomics is an important
      component of precision medicine. Informatics, especially CDS in the electronic
      health record (EHR), is a critical tool for the integration of pharmacogenomics
      into routine patient care. Effective integration of pharmacogenomic CDS into the
      EHR can address implementation challenges, including the increasing volume of
      pharmacogenomic clinical knowledge, the enduring nature of pharmacogenomic test
      results, and the complexity of interpreting results. Both passive and active CDS
      provide point-of-care information to clinicians that can guide the systematic use
      of pharmacogenomics to proactively optimize pharmacotherapy. Key considerations
      for a successful implementation have been identified; these include clinical
      workflows, identification of alert triggers, and tools to guide interpretation of
      results. These considerations, along with emerging resources from the Clinical
      Pharmacogenetics Implementation Consortium and the National Academy of Medicine,
      are described. CONCLUSION: The EHR with CDS is essential to curate
      pharmacogenomic data and disseminate patient-specific information at the point of
      care. As part of the successful implementation of pharmacogenomics into clinical
      settings, all relevant clinical recommendations pertaining to gene-drug pairs
      must be summarized and presented to clinicians in a manner that is seamlessly
      integrated into the clinical workflow of the EHR. In some situations, ancillary
      systems and applications outside the EHR may be integrated to augment the
      capabilities of the EHR.

PMID- 27864205
TI  - Evidence and resources to implement pharmacogenetic knowledge for precision
      medicine.
AB  - PURPOSE: The current state of pharmacogenetic data curation and dissemination is
      described, and evidence-based resources for applying pharmacogenetic data in
      clinical practice are reviewed. SUMMARY: Implementation of pharmacogenetics in
      clinical practice has been relatively slow despite substantial scientific
      progress in understanding linkages between genetic variation and variability of
      drug response and effect. One factor that has inhibited the adoption of genetic
      data to guide medication use is a lack of knowledge of how to translate genetic
      test results into clinical action based on currently available evidence. Other
      implementation challenges include controversy over selection of appropriate
      evidentiary thresholds for routine clinical implementation of pharmacogenetic
      data and the difficulty of compiling scientific data to support clinical
      recommendations given that large randomized controlled trials to demonstrate the
      utility of pharmacogenetic testing are not feasible or are not considered
      necessary to establish clinical utility. Organizations such as the Clinical
      Pharmacogenetics Implementation Consortium (CPIC) and the Pharmacogenomics
      Knowledgebase (PharmGKB) systematically evaluate emerging evidence of
      pharmacogenomic linkages and publish evidence-based prescribing recommendations
      to inform clinical practice. Both CPIC and PharmGKB provide online resources that
      facilitate the interpretation of genetic test results and provide prescribing
      recommendations for specific gene-drug pairs. CONCLUSION: Resources provided by
      organizations such as CPIC and PharmGKB, which use standardized approaches to
      evaluate the literature and provide clinical guidance for a growing number of
      gene-drug pairs, are essential for the implementation of pharmacogenetics into
      routine clinical practice.

PMID- 27864207
TI  - Clinical and regulatory considerations in pharmacogenetic testing.
AB  - PURPOSE: Both regulatory science and clinical practice rely on best available
      scientific data to guide decision-making. However, changes in clinical practice
      may be driven by numerous other factors such as cost. In this review, we
      reexamine noteworthy examples where pharmacogenetic testing information was added
      to drug labeling to explore how the available evidence, potential public health
      impact, and predictive utility of each pharmacogenetic biomarker impacts clinical
      uptake. SUMMARY: Advances in the field of pharmacogenetics have led to new
      discoveries about the genetic basis for variability in drug response. The Food
      and Drug Administration recognizes the value of pharmacogenetic testing
      strategies and has been proactive about incorporating pharmacogenetic information
      into the labeling of both new drugs and drugs already on the market. Although
      some examples have readily translated to routine clinical practice, clinical
      uptake of genetic testing for many drugs has been limited. CONCLUSION: Both
      regulatory science and clinical practice rely on data-driven approaches to guide
      decision making; however, additional factors are also important in clinical
      practice that do not impact regulatory decision making, and these considerations
      may result in heterogeneity in clinical uptake of pharmacogenetic testing.

PMID- 27864208
TI  - Payer view of personalized medicine.
AB  - PURPOSE: The process and methods used by payers when evaluating coverage of
      personalized medicine testing are described. SUMMARY: Personalized medicine
      encompasses a number of diagnostic tools that measure drug metabolism, genetic
      risk for disease development, and tumor type or markers that can guide oncology
      treatments. However, whole genome testing, tumor marker testing, and testing for
      drug metabolism are additional costs to the healthcare system. In order to
      justify these costs, payers and health technology assessment bodies must evaluate
      the individual tests or groups of tests on their own merits. In order for a test
      to be covered by payers, test developers must demonstrate clinical utility as
      measured by improved outcomes or well-informed decision-making. In the United
      States, payers generally focus on clinical benefit to individual patients and
      benefits to the healthcare system. Clinical benefits include improved outcomes.
      Benefits to the healthcare system are generally considered to be cost offsets,
      which may be due to reductions in the use of unnecessary interventions or to more
      efficient use of resources. Provider organizations have been assuming more
      responsibility and liability for healthcare costs through various risk
      arrangements, including accountable care organizations and patient-centered
      medical homes. Diagnostic tests that increase efficiency, reduce unnecessary
      interventions, and improve outcomes will be chosen by specialists in provider
      organizations. CONCLUSION: For personalized medicine approaches to be adopted and
      covered by health plans, the methods must be shown to be analytically and
      clinically valid and provide clinical utility at a reasonable level of cost
      effectiveness to payers.

PMID- 27864206
TI  - Educational strategies to enable expansion of pharmacogenomics-based care.
AB  - PURPOSE: The current state of pharmacogenomics education for pharmacy students
      and practitioners is discussed, and resources and strategies to address
      persistent challenges in this area are reviewed. SUMMARY: Consensus-based
      pharmacist competencies and guidelines have been published to guide
      pharmacogenomics knowledge attainment and application in clinical practice.
      Pharmacogenomics education is integrated into various pharmacy school courses
      and, increasingly, into Pharm.D. curricula in the form of required standalone
      courses. Continuing-education programs and a limited number of postgraduate
      training opportunities are available to practicing pharmacists. For colleges and
      schools of pharmacy, identifying the optimal structure and content of
      pharmacogenomics education remains a challenge; insufficient numbers of faculty
      members with pharmacogenomics expertise and the inadequate availability of
      practice settings for experiential education are other limiting factors.
      Strategies for overcoming those challenges include providing early exposure to
      pharmacogenomics through foundational courses and incorporating pharmacogenomics
      into practice-based therapeutics courses and introductory and advanced pharmacy
      practice experiences. For practitioner education, online resources, clinical
      decision support-based tools, and certificate programs can be used to supplement
      structured postgraduate training in pharmacogenomics. Recently published data
      indicate successful use of "shared curricula" and participatory education models
      involving opportunities for learners to undergo personal genomic testing.
      CONCLUSION: The pharmacy profession has taken a leadership role in expanding
      student and practitioner education to meet the demand for increased pharmacist
      involvement in precision medicine initiatives. Effective approaches to teaching
      pharmacogenomics knowledge and driving its appropriate application in clinical
      practice are increasingly available.

PMID- 27864210
TI  - Summaries of safety labeling changes approved by FDA-boxed warnings highlights,
      July-September 2016.

PMID- 27864209
TI  - Pharmacists should jump onto the clinical pharmacogenetics train.

PMID- 27864212
TI  - Rosalind Mary Maskell.

PMID- 27864213
TI  - Many US patients are hit with surprise emergency care bills, study finds.

PMID- 27864214
TI  - Vasculitic neuropathy induced by pembrolizumab.

PMID- 27864215
TI  - Atrophic exocrine pancreatic insufficiency associated with anti-PD1 therapy.

PMID- 27864217
TI  - Risk of second malignant neoplasms in women and girls with germ cell tumors.
AB  - Background: While an elevated risk of second malignant neoplasms (SMNs) has been
      observed in men treated for germ cell tumors (GCTs), risk of SMNs have not been
      quantified in adult women or in girls treated for GCTs. Patients and methods: One
      year survivors of primary GCTs diagnosed between January 1980 and December 2012
      were identified from Surveillance, Epidemiology, and End Results (SEER 9)
      registries. Risk of SMNs was calculated using SEER*Stat. Results: Among 1507
      patients, a total of 47 SMNs were identified. The overall risk of SMNs was not
      elevated in females overall or in females treated for GCT during adulthood
      although SMN sites (pancreas, soft tissue, bladder, kidney, and thyroid) and
      trends were comparable with those in men. There were too few childhood GCT cases
      with SMNs for further analysis. Conclusions: Unlike men, women treated for GCTs
      did not have a statistically significant elevated risk of SMNs [standardized
      incidence ratio = 1.11; 95% confidence interval (CI) = 0.81-1.47]. The fact that
      SMNs in women occur in sites similar to those observed in men indicate that long
      term follow-up of a larger cohort of females treated for GCT is warranted.

PMID- 27864218
TI  - Second primary malignancies in multiple myeloma: an overview and IMWG consensus.
AB  - Background: Therapeutic advancements following the introduction of autologous
      stem cell transplantation and 'novel' agents have significantly improved clinical
      outcomes for patients with multiple myeloma (MM). Increased life expectancy,
      however, has led to renewed concerns about the long-term risk of second primary
      malignancies (SPMs). This review outlines the most up-to-date knowledge of
      possible host-, disease-, and treatment-related risk factors for the development
      of SPMs in patients with MM, and provides practical recommendations to assist
      physicians. Design: A Panel of International Myeloma Working Group members
      reviewed the most relevant data published in the literature as full papers, or
      presented at meetings of the American Society of Clinical Oncology, American
      Society of Hematology, European Hematology Association, or International Myeloma
      Workshops, up to June 2016. Here, we present the recommendations of the Panel,
      based on this literature review. Results: Overall, the risk of SPMs in MM is low,
      multifactorial, and partially related to the length of patients' survival and MM
      intrinsic susceptibility. Studies suggest a significantly increased incidence of
      SPMs when lenalidomide is administered either following, or concurrently with,
      oral melphalan. Increased SPM incidence has also been reported with lenalidomide
      maintenance following high-dose melphalan, albeit to a lesser degree. In both
      cases, the risk of death from MM was significantly higher than the risk of death
      from SPMs, with lenalidomide possibly providing a survival benefit. No increase
      in SPM incidence was reported with lenalidomide plus dexamethasone (without
      melphalan), or with bortezomib plus oral melphalan, dexamethasone, or
      thalidomide. Conclusion: In general, the risk of SPMs should not alter the
      current therapeutic decision-making process in MM. However, regimens such as
      lenalidomide plus dexamethasone should be preferred to prolonged exposure to
      lenalidomide plus oral melphalan. SPM risk should be carefully discussed with the
      patient in the context of benefits and risks of different treatment options.

PMID- 27864222
TI  - Johan Willem Rademaker.

PMID- 27864216
TI  - Resistance to anticancer immunity in cancer patients: potential strategies to
      reverse resistance.
AB  - In the 1990s, the application of immunotherapy approaches to target cancer cells
      resulted in significant clinical responses in patients with advanced malignancies
      who were refractory to conventional therapies. While early immunotherapeutics
      were focused on T cell-mediated cytotoxic activity, subsequent efforts were
      centered on targeted antibody-mediated anticancer therapy. The initial success
      with antibody therapy encouraged further studies and, consequently, there are now
      more than 25 FDA-approved antibodies directed against a range of targets.
      Although both T cell and antibody therapies continue to result in significant
      clinical responses with minimal toxicity, a significant subset of patients does
      not respond to immunotherapy and another subset develops resistance following an
      initial response. This review is focused on describing examples showing that
      cancer resistance to immunotherapies indeed occurs. In addition, it reviews the
      mechanisms being used to overcome the resistance to immunotherapies by targeting
      the tumor cell directly and/or the tumor microenvironment.

PMID- 27864220
TI  - Estimating 12-week death probability in patients with refractory metastatic
      colorectal cancer: the Colon Life nomogram.
AB  - Background: Regorafenib and TAS-102 have recently demonstrated statistically
      significant survival gains in patients with refractory metastatic colorectal
      cancer (mCRC). Life expectancy >=12 weeks was an inclusion criterion in
      registrative trials, and the identification of proper clinical selection tools
      for the daily use of these drugs in heavily pre-treated patients is needed to
      improve the cost-benefit ratio. We aimed at building a nomogram able to predict
      death probability within 12 weeks from the date of assessment of refractory mCRC.
      Patients and methods: Four hundred eleven refractory mCRC patients with ECOG
      performance status (PS) <=2 receiving regorafenib, TAS-102 or other treatments
      were used as developing set. Putative prognostic variables were selected using a
      random forest model and included in a binary logistic model from which the
      nomogram was developed. The nomogram was externally validated and its performance
      was evaluated by examining calibration (how close predictions were to the actual
      outcome) and discriminative ability (Harrell C index) both on developing
      (internal validation) and validating (external validation) sets. Results: Four
      variables were selected and included in the nomogram: PS (P < 0.0001), primary
      tumor resection (P = 0.027), LDH value (P = 0.0001) and peritoneal involvement (P
      = 0.081). In the developing set, the nomogram discriminative ability was high (C
      = 0.778), and was confirmed in the validating set (C = 0.778), where the overall
      outcome was better as a consequence of the enrichment in patients receiving
      regorafenib or TAS-102 (46% versus 34%; P < 0.0001). Conclusions: Our nomogram
      may be a useful tool to predict the probability of death within 12 weeks in
      patients with refractory mCRC. Based on four easy-to-collect variables, the
      'Colon Life' nomogram and free app for smartphones may improve mCRC patients'
      selection for later-line therapies and assist researchers for the enrollment in
      clinical trials in this setting.

PMID- 27864219
TI  - Neoadjuvant chemotherapy (NACT) increases immune infiltration and programmed
      death-ligand 1 (PD-L1) expression in epithelial ovarian cancer (EOC).
AB  - Background: Lymphocytic infiltration at diagnosis is prognostic in EOC, however,
      the impact of NACT on tumour infiltrating lymphocytes (TILs) or PD-L1 expression
      remains poorly described. Patients and methods: Patients with EOC and sequential
      samples (pre-NACT, post-NACT or relapse) were retrospectively identified. TILs
      were evaluated on whole sections; stromal TILs (sTILs) scored as percentage of
      stromal area with high sTILs defined as >=50%; intra-epithelial TILs (ieTILs)
      scored semi-quantitatively (0-3) with high ieTILs >=2. A smaller number were
      available for PD-L1 evaluation, cut-off for positivity was >=5% staining.
      Results: sTILs were detected in all tumours at diagnosis (range 2-90%, median
      20%), with 22% (25/113) showing high sTILs. Among evaluable paired pre/post-NACT
      samples (N = 83), an overall increase in median sTILs from 20% to 30% was seen
      following NACT (P = 0.0005); individually the impact of NACT varied with sTILs
      increasing in 51% (42/83), decreasing in 25%, and stable in 24%. Post-NACT sTILs
      were predictive of platinum-free interval (PFI), patients with PFI >=6 months had
      significantly higher post-NACT sTILs (sTILs 28% versus 18% for PFI <6 months, P =
      0.026); pre-NACT sTILS were not predictive. At diagnosis, 23% showed high ieTILs,
      and following NACT 33% showed increasing ieTILs. Proportion of tumours with PD-L1
      positive immune cells was 30% (15/50) pre-NACT and 53% (27/51) post-NACT (P =
      0.026). Among paired tumours, 63% of PD-L1-negative tumours became positive after
      NACT, furthermore cisplatin induced PD-L1 expression in PD-L1-negative EOC cell
      lines. On multivariate analysis, high sTILs both pre- and post-NACT were
      independent prognostic factors for progression-free survival (PFS) (HR 0.49, P =
      0.02 and HR 0.60, P = 0.05, respectively). No prognostic impact of ieTILs or PD
      L1 expression was detected. Conclusions: In EOC, sTILs levels are prognostic at
      diagnosis and remain prognostic after NACT. TILs and PD-L1 expression increase
      following NACT. Evaluation of immune parameters in the post-NACT tumour may help
      select patients for immunotherapy trials.

PMID- 27864223
TI  - Field evidence of strong differential pollen placement by Old World bat
      pollinated plants.
AB  - BACKGROUND AND AIMS: Sympatric plant species that share pollinators potentially
      compete for pollination and risk interspecific pollen transfer, but this
      competition can be minimized when plant species place pollen on different areas
      of the pollinator's body. Multiple studies have demonstrated strong differential
      pollen placement by sympatric plant species under laboratory conditions; however,
      field evidence collected in natural settings is less common. Furthermore, it is
      unknown whether precise pollen placement on the pollinator's body remains
      constant throughout the foraging period, or if such patterns become diffused over
      time (e.g. due to grooming). To test the prevalence of differential pollen
      placement in the wild, we examined a community of five night-blooming plant
      species in southern Thailand that share common bat pollinators. METHODS: We mist
      netted wild foraging nectar bats and collected pollen samples from four body
      parts: the crown of the head, face, chest and ventral side of one wing. We also
      noted the time of pollen collection to assess how pollinator pollen loads change
      throughout the foraging period. KEY RESULTS: Our findings revealed that most of
      our plant study species placed pollen on precise areas of the bat, consistent
      with experimental work, and that patterns of differential pollen placement
      remained constant throughout the night. CONCLUSIONS: This study demonstrates how
      diverse floral morphologies effectively limit interspecific pollen transfer among
      Old World bat-pollinated plants under natural conditions. Additionally,
      interspecific pollen transfer is probably minimal throughout the entire foraging
      period, since patterns of pollen on the bats' bodies were consistent over time.

PMID- 27864226
TI  - Pinpointing Cancer Stem Cells in Oligodendroglioma.
AB  - Through single-cell RNA sequencing of low-grade oligodendrogliomas, researchers
      have identified a cell population featuring a gene expression signature similar
      to those of neural stem and progenitor cells. These cancer stem cells have
      enriched proliferative potential and may be responsible for fueling the growth of
      this glioma subtype.

PMID- 27864224
TI  - Infection by Rhodococcus fascians maintains cotyledons as a sink tissue for the
      pathogen.
AB  - Background and Aims: Pisum sativum L. (pea) seed is a source of carbohydrate and
      protein for the developing plant. By studying pea seeds inoculated by the
      cytokinin-producing bacterium, Rhodococcus fascians , we sought to determine the
      impact of both an epiphytic (avirulent) strain and a pathogenic strain on source
      sink activity within the cotyledons during and following germination. Methods:
      Bacterial spread was monitored microscopically, and real-time reverse
      transcription-quantitative PCR was used to determine the expression of cytokinin
      biosynthesis, degradation and response regulator gene family members, along with
      expression of family members of SWEET , SUT , CWINV and AAP genes - gene families
      identified initially in pea by transcriptomic analysis. The endogenous cytokinin
      content was also determined. Key Results: The cotyledons infected by the virulent
      strain remained intact and turned green, while multiple shoots were formed and
      root growth was reduced. The epiphytic strain had no such marked impact.
      Isopentenyl adenine was elevated in the cotyledons infected by the virulent
      strain. Strong expression of RfIPT , RfLOG and RfCKX was detected in the
      cotyledons infected by the virulent strain throughout the experiment, with
      elevated expression also observed for PsSWEET , PsSUT and PsINV gene family
      members. The epiphytic strain had some impact on the expression of these genes,
      especially at the later stages of reserve mobilization from the cotyledons.
      Conclusions: The pathogenic strain retained the cotyledons as a sink tissue for
      the pathogen rather than the cotyledon converting completely to a source tissue
      for the germinating plant. We suggest that the interaction of cytokinins, CWINVs
      and SWEETs may lead to the loss of apical dominance and the appearance of
      multiple shoots.

PMID- 27864228
TI  - IFNgamma Mutations Prompt CTLA-4 Inhibitor Resistance.
AB  - A recent study pinpoints loss of IFNgamma signaling as one reason why many
      patients do not respond to the CTLA-4 inhibitor ipilimumab. Analyzing whole-exome
      tumor sequencing data from 16 patients with melanoma, the researchers found
      multiple copy-number alterations that led to the loss of key IFNgamma pathway
      genes in 12 ipilimumab nonresponders. Mice bearing melanoma tumors that lacked
      one of these genes, IFNGR1, also had an impaired response to anti-CTLA-4 therapy
      and significantly reduced overall survival, compared with their counterparts
      whose tumors had intact IFNGR1.

PMID- 27864225
TI  - Should I fight or should I grow now? The role of cytokinins in plant growth and
      immunity and in the growth-defence trade-off.
AB  - Background: Perception and activation of plant immunity require a remarkable
      level of signalling plasticity and control. In Arabidopsis and other plant
      species, constitutive defence activation leads to resistance to a broad spectrum
      of biotrophic pathogens, but also frequently to stunted growth and reduced seed
      set. Plant hormones are important integrators of the physiological responses that
      influence the outcome of plant-pathogen interactions. Scope: We review the
      mechanisms by which the plant hormone cytokinin regulates both plant growth and
      response to pathogens, and how cytokinins may connect these two processes,
      ultimately affecting the growth trade-offs observed in plant immunity.

PMID- 27864232
TI  - Bringing Precision Medicine to Community Oncologists.
AB  - Quest Diagnostics has teamed up with Memorial Sloan Kettering Cancer Center and
      IBM Watson Health to offer IBM Watson Genomics to its network of community cancer
      centers and hospitals. This new service aims to advance precision medicine by
      combining genomic tumor sequencing with the power of cognitive computing.

PMID- 27864233
TI  - Aging is associated with impaired angiogenesis, but normal microvascular network
      structure, in the rat mesentery.
AB  - : A big problem associated with aging is thought to be impaired microvascular
      growth or angiogenesis. However, to link the evidence for impaired angiogenesis
      to microvascular dysfunction in aged tissues, we must compare adult vs. aged
      microvascular networks in unstimulated scenarios. The objective of this study was
      to test the hypothesis that aged microvascular networks are characterized by both
      fewer vessels and the impaired ability to undergo angiogenesis. Mesentery tissues
      from adult (9-mo) and aged (24-mo) male Fischer 344 rats were harvested and
      immunolabeled for platelet/endothelial cell adhesion molecule (an endothelial
      cell marker) according to two scenarios: unstimulated and stimulated. For
      unstimulated groups, tissues harvested from adult and aged rats were compared.
      For stimulated groups, tissues were harvested 3 or 10 days after compound 48/80
      induced mast cell degranulation stimulation. Unstimulated aged microvascular
      networks displayed larger mean vascular area per tissue area compared with the
      unstimulated adult networks. The lack of a decrease in vessel density was
      supported at the gene expression level with RNA-Seq analysis and with comparison
      of vessel densities in soleus muscle. Following stimulation, capillary sprouting
      and vessel density were impaired in aged networks at 3 and 10 days, respectively.
      Our results suggest that aging associated with impaired angiogenesis mechanisms
      might not influence normal microvascular function, since unstimulated aged
      microvascular networks can display a "normal adult-like" vessel density and
      architecture. NEW & NOTEWORTHY: Using a multidimensional approach, we present
      evidence supporting that aged microvascular networks display vessel density and
      patterning similar to adult networks despite also being characterized by a
      decreased capacity to undergo angiogenesis. Thus, vessel loss is not necessarily
      a characteristic of aging.

PMID- 27864234
TI  - Interruption of perivascular sympathetic nerves of cerebral arteries offers
      neuroprotection against ischemia.
AB  - : Sympathetic nervous system activity is increased after cardiopulmonary arrest,
      resulting in vasoconstrictor release from the perivascular sympathetic nerves of
      cerebral arteries. However, the pathophysiological function of the perivascular
      sympathetic nerves in the ischemic brain remains unclear. A rat model of global
      cerebral ischemia (asphyxial cardiac arrest, ACA) was used to investigate
      perivascular sympathetic nerves of cerebral arteries via bilateral
      decentralization (preganglionic lesion) of the superior cervical ganglion (SCG).
      Decentralization of the SCG 5 days before ACA alleviated hypoperfusion and
      afforded hippocampal neuroprotection and improved functional outcomes. These
      studies can provide further insights into the functional mechanism(s) of the
      sympathetic nervous system during ischemia. NEW & NOTEWORTHY: Interruption of the
      perivascular sympathetic nerves can alleviate CA-induced hypoperfusion and
      neuronal cell death in the CA1 region of the hippocampus to enhance functional
      learning and memory.

PMID- 27864235
TI  - L5-LDL from ST-elevation myocardial infarction patients induces IL-1beta
      production via LOX-1 and NLRP3 inflammasome activation in macrophages.
AB  - : L5-LDL, the most electronegative LDL associated with major cardiovascular
      risks, significantly rises in patients with ST-segment elevation myocardial
      infarction (STEMI). The inflammatory nature of atherosclerotic vascular diseases
      has prompted us to investigate whether L5-LDL induces the production of
      inflammatory cytokines, especially vascular ischemia-related interleukin (IL)
      1beta, in the pathogenesis of STEMI. Clinical data showed that plasma levels of
      L5-LDL and IL-1beta were higher in the STEMI patients than in the controls (P <
      0.05). In THP-1-derived human macrophages, L5-LDL significantly increased the
      levels of both IL-1beta and cleaved caspase-1, indicating the activation of NOD
      like receptor pyrin domain containing 3 (NLRP3) inflammasomes by L5-LDL.
      Knockdown of NLRP3 and its adaptor protein apoptosis-associated speck-like
      protein containing a CARD (ASC) resulted in decreased L5-LDL-induced IL-1beta.
      Furthermore, knock down of the lectin-type oxidized LDL receptor (LOX-1) in THP-1
      cells attenuated L5-LDL-induced activation of NF-kappaB and caspase-1, leading to
      subsequent inhibition of IL-1beta in macrophages. Furthermore, blockade LOX-1
      with neutralizing antibody also inhibited L5-LDL-induced IL-1beta in human
      peripheral blood mononuclear cell-derived macrophages. In conclusion, L5-LDL
      induces IL-1beta production in macrophages by activation of NF-kappaB and caspase
      1 through the LOX-1-dependent pathway. This study represents the evidence linking
      L5-LDL and the inflammatory cytokine IL-1beta in STEMI, and identifies L5-LDL as
      a novel therapeutic target in acute myocardial infarction. NEW & NOTEWORTHY: This
      study represents the evidence linking L5-LDL and the inflammatory cytokine IL
      1beta in ST-segment elevation myocardial infarction (STEMI). We elucidate the
      molecular mechanism underlying L5-LDL-induced production of IL-1beta in
      macrophages. The results showed that L5-LDL induced activation of caspase-1 and
      NF-kappaB through the lectin-type oxidized LDL receptor (LOX-1)-dependent
      pathway, leading to the production of IL-1beta.

PMID- 27864237
TI  - Effect of selected clinical trial publication on adjunctive nonstatin medication
      prescribing in the Veterans Health Administration system.
AB  - PURPOSE: The question of whether publication of selected clinical trials is
      temporally followed by changes in prescribing of adjunctive lipid-lowering
      medications was evaluated. METHODS: In this retrospective preanalysis and
      postanalysis, Veterans Health Administration (VHA) patients 18 years or older who
      received a new or renewed order for any lipid-lowering medication between April
      2, 2004, and September 2, 2014, were included. This period was chosen based on
      the publication dates of three trials investigating the efficacy of nonstatin
      medications: Simvastatin with or without Ezetimibe in Familial
      Hypercholesterolemia (ENHANCE, April 3, 2008), Effects of Combination Lipid
      Therapy in Type 2 Diabetes Mellitus (ACCORD Lipid, March 14, 2010), and Niacin in
      Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy (AIM
      HIGH, December 15, 2011). Annual prescribing rates for ezetimibe, fibrates, and
      niacin were analyzed for 4 years before and after the ENHANCE, ACCORD, and AIM
      HIGH trial publication dates, respectively (3 years for niacin in AIM-HIGH) and
      reported as percent of patients in the cohort. RESULTS: Among patients receiving
      lipid-lowering medications, relatively low overall prescribing rates were
      observed for all three target medications. Prescribing rates for each medication
      decreased after its respective trial publication, with ezetimibe having the
      greatest change. CONCLUSION: Prescribing of fibrates, niacin, and ezetimibe in
      the VHA system decreased after the publication of landmark trials assessing their
      addition to a statin, consistent with the recommendations in the 2013 American
      College of Cardiology/American Heart Association (ACC/AHA) guideline, which did
      not encourage routine use of adjunctive therapies to lower the risk of
      cardiovascular disease.

PMID- 27864236
TI  - Evaluation of adherence to current guidelines for treatment of hyperlipidemia in
      adults in an outpatient setting.
AB  - PURPOSE: Adherence to the 2013 American College of Cardiology (ACC)/American
      Heart Association (AHA) cholesterol guideline at an outpatient clinic was
      evaluated. METHODS: This retrospective chart review study was conducted from
      December 1, 2013, through November 30, 2014, at an urban outpatient clinic.
      Estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk was
      calculated based on the pooled cohort equation for all patients. Patients were
      categorized into one of four statin-benefit groups, in descending order of ASCVD
      risk. The recommended intensity of a statin and the therapeutic response were
      determined for each patient. If statin therapy was indicated, patients were
      assigned to the moderate-intensity, moderate- or high-intensity, or high
      intensity group according to guideline recommendations. These guideline
      recommended statin intensities were then compared to the patient's prescribed
      statin to determine guideline concordance. Therapeutic response, expressed as the
      percent decrease in low-density lipoprotein cholesterol, was determined based on
      recommended statin intensity. RESULTS: A total of 255 patients were initiated on
      statin therapy; 193 were included for data analysis. Overall adherence to the
      guideline was 65.8%, with the highest rate in the group of patients with the
      lowest risk of ASCVD (97.8%). The group with the lowest rate of adherence to
      recommendations was patients with clinical ASCVD (46.9%). Only 31.6% of patients
      had a follow-up lipid panel performed, and even fewer achieved a therapeutic
      response. CONCLUSION: A majority of patients were initiated on the appropriate
      intensity of statin therapy according to the ACC/AHA cholesterol guideline. Of
      the small number of patients who had follow-up visits, few achieved a therapeutic
      response based on their prescribed statin therapy.

PMID- 27864238
TI  - Outcomes of a pharmacist-managed glucose collaborative practice agreement.
AB  - PURPOSE: The impact of a pharmacist-managed glucose collaborative practice
      agreement (CPA) on glycemic control at a tertiary medical center was
      investigated. METHODS: A retrospective data analysis was performed on
      hospitalized, noncritically ill patients admitted between December 2012 and June
      2014 who received at least one dose of subcutaneous insulin and experienced at
      least one blood glucose concentration of 140 mg/dL or higher. The study
      population was divided into cohorts based on admittance before versus after
      implementation of the CPA, as well as glucose management by pharmacist versus
      nonpharmacist provider. The primary endpoint of the study was glycemic control,
      defined as the percentage of total admitted days spent within a goal blood
      glucose range of 70-180 mg/dL. Secondary endpoints included the rate of
      hypoglycemia (less than 70 mg/dL), the rate of severe hypoglycemia (less than 40
      mg/dL), the rate of severe hyperglycemia (greater than 300 mg/dL), the length of
      stay, and workload metrics. RESULTS: A total of 5146 patients were included in
      the study. There was no statistically significant difference in glycemic control
      across all cohorts (p > 0.05). Secondary outcomes showed no statistically
      significant differences in the rates of hypoglycemia, severe hypoglycemia, and
      severe hyperglycemia across all cohorts. There was a significantly longer length
      of stay in the pharmacist-managed cohort (p < 0.001). Workload metrics indicated
      a 25.8% increase in the number of pharmacist-managed glucose consults post-CPA
      implementation. CONCLUSION: Pharmacists at a tertiary medical center were able to
      provide an inpatient glucose management service that maintained similar glycemic
      control for patients with diabetes as nonpharmacist providers.

PMID- 27864239
TI  - Development and implementation of a pharmacist-run comprehensive medication
      review program in Wisconsin.
AB  - PURPOSE: The development and implementation of a centralized, pharmacist-run
      population health program were pursued within a health system to increase patient
      exposure to comprehensive medication reviews (CMRs) and improve visit processes.
      SUMMARY: Program implementation included choosing appropriate pilot pharmacy
      locations, developing a feasible staffing model, standardizing the workflow, and
      creating a patient referral process. The impact on patient exposure, specific
      interventions, and the sustainability of the program were evaluated over a seven
      month period. A total of 96 CMRs were scheduled during the data collection
      period. Attendance at scheduled CMRs was 54% (52 visits); there were 25
      cancellations (26%) and 19 no-shows (20%). Since program implementation, there
      has been more than a twofold increase (2.08) in the number of CMRs completed
      within the health system. On average, all aspects of each patient visit took 1.78
      hours to complete. Pharmacists spent 28% of scheduled time on CMR tasks and 72%
      of time on telephone calls and technical tasks to maintain appointments.
      CONCLUSION: A pharmacist-run CMR program helped to elevate the role of the
      community pharmacist in a health system and to improve patient exposure to CMRs.
      Sustaining a centralized CMR program requires support from other members of the
      health-system team so that pharmacists can spend more time providing patient care
      and less time on the technical tasks involved.

PMID- 27864240
TI  - New Horizons in orthostatic hypotension.
AB  - Background: orthostatic hypotension (OH) is a common disabling condition
      associated with increased morbidity and mortality. Much of the evidence available
      is derived from younger populations with chronic neurological disease leading to
      uncertainty for the diagnosis and management of older people. Objective: to
      provide an overview of recent and emerging evidence for the diagnosis, management
      and prognosis of OH in older persons. Methods: a narrative review of recent
      studies, emerging therapies and relevant regulatory updates. Findings: revisions
      to the diagnostic criteria for OH include the duration of the blood pressure
      drop, specific criteria for initial and delayed OH and OH with hypertension. Non
      drug therapies remain the first-line treatment option and Comprehensive Geriatric
      Assessment appears to result in lower rates of OH. Recent evidence concerning
      withdrawal of causative medication is inconsistent. Midodrine has recently become
      the only licenced medication for OH in the UK. Other emerging treatments include
      atomoxetine and droxidopa but these require further evaluation. Many other agents
      may be used but are not supported by high-quality evidence. The increase in
      mortality associated with OH is less apparent in older people. Summary: OH
      remains common in older people, the new diagnostic criteria address some of the
      previous uncertainty but evidence concerning withdrawal of antihypertensives is
      conflicting. Midodrine is now the only licenced medication for OH in the UK, but
      non-drug therapies remain first line and fludrocortisone may be considered before
      midodrine. We may see other agents such as droxidopa becoming increasingly used
      over the coming years.

PMID- 27864242
TI  - Understanding the delayed prescribing of antibiotics for respiratory tract
      infection in primary care: a qualitative analysis.
AB  - OBJECTIVE: To identify general practitioner (GP) views and understanding on the
      use of delayed prescribing in primary care. DESIGN: Qualitative semistructured
      telephone interview study. SETTING: Primary care general practices in England.
      PARTICIPANTS: 32 GPs from identified high-prescribing and low-prescribing general
      practices in England. METHOD: Semistructured telephone interviews were conducted
      with GPs identified from practices within clinical commissioning groups with the
      highest and lowest prescribing rates in England. A thematic analysis of the data
      was conducted to generate themes. RESULTS: All GPs had a good understanding of
      respiratory tract infection (RTI) management and how the delayed prescribing
      approach could be used in primary care. However, GPs highlighted factors that
      were influential as to whether delayed prescribing was successfully carried out
      during the consultation. These included the increase in evidence of antimicrobial
      resistance, and GPs' prior experiences of using delayed prescribing during the
      consultation. The patient-practitioner relationship could also influence
      treatment outcomes for RTI, and a lack of an agreed prescribing strategy within
      and between practices was considered to be of significance to GPs. Participants
      expressed that a lack of feedback on prescribing data at an individual and
      practice level made it difficult to know if delayed prescribing strategies were
      successful in reducing unnecessary consumption. GPs agreed that coherent and
      uniform training and guidelines would be of some benefit to ensure consistent
      prescribing throughout the UK. CONCLUSIONS: Delayed prescribing is encouraged in
      primary care, but is not always implemented successfully. Greater uniformity
      within and between practices in the UK is needed to operationalise delayed
      prescribing, as well as providing feedback on the uptake of antibiotics. Finally,
      GPs may need further guidance on how to answer the concerns of patients without
      interpreting these questions as a demand for antibiotics, as well as educating
      the patient about antimicrobial resistance and supporting a good patient
      practitioner relationship.

PMID- 27864241
TI  - Retrospective analysis of age-adjusted body mass index among pre-pregnant women
      in the Lithuanian urban area during three decades.
AB  - BACKGROUND: The prevalence of maternal obesity at the beginning of pregnancy is
      increasing. However, there are some studies reporting the stabilisation of
      obesity epidemic or even the downward trend in the general population. OBJECTIVE:
      To determine the prevalence of overweight and obesity in Lithuanian pre-pregnant
      women during 3 decades. METHODS: This observational retrospective study included
      a sample of 2827, women aged 18-44 years who gave birth in 1987-1989, 1996-1997
      and 2007-2010: 861 (30.5%), 995 (35.2%) and 971 (34.3%), respectively. All women
      were divided into groups by body mass index (BMI) calculated from self-reported
      weight and height, and age reported during the first antenatal visit.
      Quantitative parametric variables were expressed as mean and SD; qualitative
      variables, as absolute numbers (n) and percentage (%). For parametric data,
      analysis of variance (ANOVA) was used. Differences were considered statistically
      significant at p<0.05. RESULTS: The prevalence of overweight and obesity among
      women aged 18-24 years decreased from 20.9% in 1987-1989 to 9.5% in 1996-1997 but
      increased to 15.7% in 2007-2010; among women aged 25-34 years, decreased from
      35.5% in 1987-1989 to 23% in 1996-1997 and to 22.4% in 2007-2010; and among women
      aged 35-44 years decreased from 64.9% in 1987-1989 to 34% in 1996-1997 but
      increased to 45.3% in 2007-2010. BMI increased with an increasing age (r=0.254,
      p<0.05). Analysis by separate periods (1987-1989, 1996-1997 and 2007-2010)
      revealed a positive correlation between BMI and age at the first antenatal visit
      in all periods (r=0.325, p<0.01; r=0.266, p<0.01; and r=0.210, p<0.01,
      respectively). CONCLUSIONS: The prevalence of overweight and obesity among pre
      pregnant women tended to decrease in the Lithuanian urban area during 3 decades.
      A slight increase in overweight and obesity documented in 2007-2010 compared with
      1996-1997 most likely was caused by older maternal age.

PMID- 27864243
TI  - Determinants of the sustained employment of physician assistants in hospitals: a
      qualitative study.
AB  - OBJECTIVES: To identify determinants of the initial employment of physician
      assistants (PAs) for inpatient care as well as of the sustainability of their
      employment. DESIGN: We conducted a qualitative study with semistructured
      interviews with care providers. Interviews continued until data saturation was
      achieved. All interviews were transcribed verbatim. A framework approach was used
      for data analysis. Codes were sorted by the themes, bringing similar concepts
      together. SETTING: This study was conducted between June 2014 and May 2015 within
      11 different hospital wards in the Netherlands. The wards varied in medical
      speciality, as well as in hospital type and the organisational model for
      inpatient care. PARTICIPANTS: Participant included staff physicians, residents,
      PAs and nurses. RESULTS: The following themes emerged to be important for the
      initial employment of PAs and the sustainability of their employment: the
      innovation, individual factors, professional interactions, incentives and
      resources, capacity for organisational change and social, political and legal
      factors. CONCLUSIONS: 10 years after the introduction of PAs, there was little
      discussion among the adopters about the added value of PAs, but organisational
      and financial uncertainties played an important role in the decision to employ
      and continue employment of PAs. Barriers to employ and continue PA employment
      were mostly a consequence of locally arranged restrictions by hospital management
      and staff physicians, as barriers regarding national laws, PA education and
      competencies seemed absent.

PMID- 27864244
TI  - Impact of smoking on fertility and age of menopause: a population-based
      assessment.
AB  - BACKGROUND AND AIMS: Studies in patients seeking medically assisted reproduction
      have shown that smoking reduces fertility, but little information is available in
      the general population. We assessed the associations between smoking and the
      number of children, childbearing planning and age at menopause in a
      representative sample of the population of Lausanne, Switzerland. METHODS: Data
      from 6711 participants (3530 women, age range 35-75 years) collected between 2003
      and 2006 and again in 2009 and 2012. Smoking status, number of offsprings and age
      of menopause were assessed. RESULTS: Women who currently smoke had significantly
      less children than former or never smokers: the number of children per women
      (average+/-SD) was 1.38+/-1.05, 1.45+/-1.07 and 1.576+/-1.16, respectively
      (p<0.001). Women who currently smoke had their first child at an earlier age than
      the others: 26.7+/-5.2, 27.4+/-5.4 and 26.9+/-5.2 years old for current, former
      and never smokers, respectively, (p=0.01). Similar findings were found for men:
      number of children per men 1.475+/-1.16, 1.67+/-1.13 and 1.55+/-1.22 for current,
      former and never smokers, respectively (p<0.001); no difference was found
      regarding age at the first child. The difference persisted after multivariate
      adjustment (adjusted for age, body mass index, Caucasian origins, alcohol
      consumption, caffeinated drinks consumption, educational level, receiving social
      help and women taking contraceptives) for the age at first child among women. No
      association was found between Heaviness of Smoking Index and the number of
      children among current smokers in both genders. Women who smoke had their
      menopause more than 1 year prior than never-smoking women (48.9+/-0.2 years
      compared with 47.8+/-0.3 years, respectively, p=0.002). CONCLUSIONS: Smoking is
      associated with an earlier age of having the first child and of menopause among
      women.

PMID- 27864245
TI  - Social networks of men who have sex with men and their implications for HIV/STI
      interventions: results from a cross-sectional study using respondent-driven
      sampling in a large and a small city in Tanzania.
AB  - OBJECTIVE: Men who have sex with men (MSM) in sub-Saharan Africa remain hidden
      and hard to reach for involvement in HIV and sexually transmitted infection (STI)
      services. The aim of the current study was to describe MSM social networks in a
      large and a small Tanzanian city in order to explore their utility for peer-based
      healthcare interventions. METHODS: Data were collected through respondent-driven
      sampling (RDS) in Dar es Salaam (n=197) and in Tanga (n=99) in 2012 and 2013,
      using 5 and 4 seeds, respectively. All results were adjusted for RDS sampling
      design. RESULTS: Mean personal network size based on the number of MSM who were
      reported by the participants, as known to them was 12.0+/-15.5 in Dar es Salaam
      and 7.6+/-8.1 in Tanga. Mean actual RDS network size was 39.4+/-31.4 in Dar es
      Salaam and 25.3+/-9.7 in Tanga. A majority (97%) reported that the person from
      whom they received the recruitment coupon was a sexual partner, close friend or
      acquaintance. Homophile in recruitment patterns (selective affiliation) was
      present for age, gay openness, and HIV status in Dar es Salaam, and for sexual
      identification in Tanga. CONCLUSIONS: The personal network sizes and existence of
      contacts between recruiter and referral indicate that it is possible to use peer
      driven interventions to reach MSM for HIV/STI interventions in larger and smaller
      sub-Saharan African cities. The study was reviewed and approved by the University
      of Texas Health Science Center's Institutional Review Board (HSC-SPH-10-0033) and
      the Tanzanian National Institute for Medical Research (NIMR/HQ/R.8a/Vol.
      IX/1088).

PMID- 27864246
TI  - Preventing postnatal maternal mental health problems using a psychoeducational
      intervention: the cost-effectiveness of What Were We Thinking.
AB  - OBJECTIVES: Postnatal maternal mental health problems, including depression and
      anxiety, entail a significant burden globally, and finding cost-effective
      preventive solutions is a public policy priority. This paper presents a cost
      effectiveness analysis of the intervention, What Were We Thinking (WWWT), for the
      prevention of postnatal maternal mental health problems. DESIGN: The economic
      evaluation, including cost-effectiveness and cost-utility analyses, was conducted
      alongside a cluster-randomised trial. SETTING: 48 Maternal and Child Health
      Centres in Victoria, Australia. PARTICIPANTS: Participants were English-speaking
      first-time mothers attending participating Maternal and Child Health Centres.
      Full data were collected for 175 participants in the control arm and 184 in the
      intervention arm. INTERVENTION: WWWT is a psychoeducational intervention targeted
      at the partner relationship, management of infant behaviour and parental fatigue.
      OUTCOME MEASURES: The evaluation considered public sector plus participant out-of
      pocket costs, while outcomes were expressed in the 30-day prevalence of
      depression, anxiety and adjustment disorders, and quality-adjusted life years
      (QALYs). Incremental costs and outcomes were estimated using regression analyses
      to account for relevant sociodemographic, prognostic and clinical
      characteristics. RESULTS: The intervention was estimated to cost $A118.16 per
      participant. The analysis showed no statistically significant difference between
      the intervention and control groups in costs or outcomes. The incremental cost
      effectiveness ratios were $A36 451 per QALY gained and $A152 per percentage-point
      reduction in 30-day prevalence of depression, anxiety and adjustment disorders.
      The estimate lies under the unofficial cost-effectiveness threshold of $A55 000
      per QALY; however, there was considerable uncertainty surrounding the results,
      with a 55% probability that WWWT would be considered cost-effective at that
      threshold. CONCLUSIONS: The results suggest that, although WWWT shows promise as
      a preventive intervention for postnatal maternal mental health problems, further
      research is required to reduce the uncertainty over its cost-effectiveness as
      there were no statistically significant differences in costs or outcomes. TRIAL
      REGISTRATION NUMBER: ACTRN12613000506796; results.

PMID- 27864247
TI  - Impact of a pharmacist-delivered discharge and follow-up intervention for
      patients with acute coronary syndromes in Qatar: a study protocol for a
      randomised controlled trial.
AB  - INTRODUCTION: Acute coronary syndrome (ACS) is one of the leading causes of
      morbidity and mortality worldwide. Secondary cardiovascular risk reduction
      therapy (consisting of an aspirin, a beta-blocker, an ACE inhibitor or an
      angiotensin II receptor blocker and a statin) is needed for all patients with
      ACS. Less than 80% of patients with ACS in Qatar use this combination after
      discharge. This study is aimed to evaluate the effectiveness of clinical
      pharmacist-delivered intervention at discharge and tailored follow-up
      postdischarge on decreasing hospital readmissions, emergency department (ED)
      visits and mortality among patients with ACS. METHODS AND ANALYSIS: A
      prospective, randomised controlled trial will be conducted at the Heart Hospital
      in Qatar. Patients are eligible for enrolment if they are at least 18 years of
      age and are discharged from any non-surgical cardiology service with ACS.
      Participants will be randomised into 1 of 3 arms: (1) 'control' arm which
      includes patients discharged during weekends or after hours; (2) 'clinical
      pharmacist delivered usual care at discharge' arm which includes patients
      receiving the usual care at discharge by clinical pharmacists; and (3) 'clinical
      pharmacist-delivered structured intervention at discharge and tailored follow-up
      postdischarge' arm which includes patients receiving intensive structured
      discharge interventions in addition to 2 follow-up sessions by intervention
      clinical pharmacists. Outcomes will be measured by blinded research assistants at
      3, 6 and 12 months after discharge and will include: all-cause hospitalisations
      and cardiac-related hospital readmissions (primary outcome), all-cause mortality
      including cardiac-related mortality, ED visits including cardiac-related ED
      visits, adherence to medications and treatment burden. Percentage of readmissions
      between the 3 arms will be compared on intent-to-treat basis using chi2 test with
      Bonferroni's adjusted pairwise comparisons if needed. ETHICS AND DISSEMINATION:
      The study was ethically approved by the Qatar University and the Hamad Medical
      Corporation Institutional Review Boards. The results shall be disseminated in
      international conferences and peer-reviewed publications. TRIALS REGISTRATION
      NUMBER: NCT02648243; pre-results.

PMID- 27864248
TI  - The Challenge of Universal Eye Health in Latin America: distributive inequality
      of ophthalmologists in 14 countries.
AB  - BACKGROUND: No comprehensive study currently exists on the supply of
      ophthalmologists across Latin America. We explored sociogeographic inequalities
      in the availability and distribution of ophthalmologists across 14 Latin American
      countries. METHODS: The National Ophthalmologic Societies of Argentina, Bolivia,
      Brazil, Colombia, Costa Rica, Chile, the Dominican Republic, Ecuador, Guatemala,
      Mexico, Paraguay, Peru, Uruguay and Venezuela provided data on affiliated
      ophthalmologists by first-order subnational divisions in 2013. Human Development
      Index (HDI) estimates at the corresponding subnational division were used as
      equity stratifiers. Distributional inequality of ophthalmologists within each
      country was assessed by the health concentration index (HCI) and the index of
      dissimilarity (ID), along with the mean level of ophthalmologists per population.
      RESULTS: Across all countries studied, there were 5.2 ophthalmologists per 100
      000 population on average (95% CI 5.0 to 5.4) in 2013, with a mean HCI of 0.26
      (0.16 to 0.37) and a mean relative ID of 22.7% (20.9% to 24.7%). There was wide
      inequality in ophthalmologist availability between countries, ranging from 1.2
      (1.1 to 1.4) in Ecuador to 8.6 (8.5 to 8.8) in Brazil. All countries had positive
      (ie, pro-rich) HCI values ranging from 0.68 (0.66 to 0.71) in Guatemala to 0.02 (
      0.11 to 0.14) in Venezuela. Correspondingly, redistributive potential to achieve
      equity was closest in Venezuela (ID: 1.5%) and farthest in Guatemala (ID: 60.3%).
      Benchmarked against regional averages, most countries had a lower availability of
      ophthalmologists and higher relative inequality. CONCLUSIONS: There is high
      inequality in the level and distribution of ophthalmologists between and within
      countries in Latin America, with a disproportionate number concentrated in more
      developed, socially advantaged areas. More equitable access to ophthalmologists
      could be achieved by implementing incentivised human resources redistribution
      programmes and by improving the social determinants of health in underserved
      areas.

PMID- 27864249
TI  - Positive predictive value of cardiovascular diagnoses in the Danish National
      Patient Registry: a validation study.
AB  - OBJECTIVE: The majority of cardiovascular diagnoses in the Danish National
      Patient Registry (DNPR) remain to be validated despite extensive use in
      epidemiological research. We therefore examined the positive predictive value
      (PPV) of cardiovascular diagnoses in the DNPR. DESIGN: Population-based
      validation study. SETTING: 1 university hospital and 2 regional hospitals in the
      Central Denmark Region, 2010-2012. PARTICIPANTS: For each cardiovascular
      diagnosis, up to 100 patients from participating hospitals were randomly sampled
      during the study period using the DNPR. MAIN OUTCOME MEASURE: Using medical
      record review as the reference standard, we examined the PPV for cardiovascular
      diagnoses in the DNPR, coded according to the International Classification of
      Diseases, 10th Revision. RESULTS: A total of 2153 medical records (97% of the
      total sample) were available for review. The PPVs ranged from 64% to 100%, with a
      mean PPV of 88%. The PPVs were >=90% for first-time myocardial infarction, stent
      thrombosis, stable angina pectoris, hypertrophic cardiomyopathy, arrhythmogenic
      right ventricular cardiomyopathy, takotsubo cardiomyopathy, arterial
      hypertension, atrial fibrillation or flutter, cardiac arrest, mitral valve
      regurgitation or stenosis, aortic valve regurgitation or stenosis, pericarditis,
      hypercholesterolaemia, aortic dissection, aortic aneurysm/dilation and arterial
      claudication. The PPVs were between 80% and 90% for recurrent myocardial
      infarction, first-time unstable angina pectoris, pulmonary hypertension,
      bradycardia, ventricular tachycardia/fibrillation, endocarditis, cardiac tumours,
      first-time venous thromboembolism and between 70% and 80% for first-time and
      recurrent admission due to heart failure, first-time dilated cardiomyopathy,
      restrictive cardiomyopathy and recurrent venous thromboembolism. The PPV for
      first-time myocarditis was 64%. The PPVs were consistent within age, sex,
      calendar year and hospital categories. CONCLUSIONS: The validity of
      cardiovascular diagnoses in the DNPR is overall high and sufficient for use in
      research since 2010.

PMID- 27864250
TI  - Reporting quality in abstracts of meta-analyses of depression screening tool
      accuracy: a review of systematic reviews and meta-analyses.
AB  - OBJECTIVE: Concerns have been raised regarding the quality and completeness of
      abstract reporting in evidence reviews, but this had not been evaluated in meta
      analyses of diagnostic accuracy. Our objective was to evaluate reporting quality
      and completeness in abstracts of systematic reviews with meta-analyses of
      depression screening tool accuracy, using the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) for Abstracts tool. DESIGN: Cross
      sectional study. INCLUSION CRITERIA: We searched MEDLINE and PsycINFO from 1
      January 2005 through 13 March 2016 for recent systematic reviews with meta
      analyses in any language that compared a depression screening tool to a diagnosis
      based on clinical or validated diagnostic interview. DATA EXTRACTION: Two
      reviewers independently assessed quality and completeness of abstract reporting
      using the PRISMA for Abstracts tool with appropriate adaptations made for studies
      of diagnostic test accuracy. Bivariate associations of number of PRISMA for
      Abstracts items complied with (1) journal abstract word limit and (2) A
      Measurement Tool to Assess Systematic Reviews (AMSTAR) scores of meta-analyses
      were also assessed. RESULTS: We identified 21 eligible meta-analyses. Only two of
      21 included meta-analyses complied with at least half of adapted PRISMA for
      Abstracts items. The majority met criteria for reporting an appropriate title
      (95%), result interpretation (95%) and synthesis of results (76%). Meta-analyses
      less consistently reported databases searched (43%), associated search dates
      (33%) and strengths and limitations of evidence (19%). Most meta-analyses did not
      adequately report a clinically meaningful description of outcomes (14%), risk of
      bias (14%), included study characteristics (10%), study eligibility criteria
      (5%), registration information (5%), clear objectives (0%), report eligibility
      criteria (0%) or funding (0%). Overall meta-analyses quality scores were
      significantly associated with the number of PRISMA for Abstracts scores items
      reported adequately (r=0.45). CONCLUSIONS: Quality and completeness of reporting
      were found to be suboptimal. Journal editors should endorse PRISMA for Abstracts
      and allow for flexibility in abstract word counts to improve quality of
      abstracts.

PMID- 27864251
TI  - Post hoc evaluation of a common-sense intervention for asthma management in
      community pharmacy.
AB  - OBJECTIVES: The aim was to evaluate a common-sense, behavioural change
      intervention to implement clinical guidelines for asthma management in the
      community pharmacy setting. DESIGN: The components of the common-sense
      intervention were described in terms of categories and dimensions using the
      Intervention Taxonomy (ITAX) and Behaviour Change Techniques (BCTs) using the
      Behaviour Change Wheel (BCW), Capability, Opportunity and Motivation-Behaviour
      (COM-B) System and Behaviour Change Techniques Taxonomy (BCTTv1). The
      retrospective application of these existing tools facilitated evaluation of the
      mechanism, fidelity, logistics and rationale of the common-sense intervention.
      INTERVENTION: The initial intervention study was conducted in 336 community
      pharmacies in the metropolitan area of Perth, Western Australia. Small-group
      workshops were conducted in 25 pharmacies; 162 received academic detailing and
      149 acted as controls. The intervention was designed to improve pharmacy
      compliance with guidelines for a non-prescription supply of asthma reliever
      medications. RESULTS: Retrospective application of ITAX identified mechanisms for
      the short-acting beta agonists intervention including improving knowledge,
      behavioural skills, problem-solving skills, motivation and self-efficacy. All the
      logistical elements were considered in the intervention design but the duration
      and intensity of the intervention was minimal. The intervention was delivered as
      intended (as a workshop) to 13.4% of participants indicating compromised fidelity
      and significant adaptation. Retrospective application of the BCW, COM-B system
      and BCTTv1 identified 9 different behaviour change techniques as the rationale
      for promoting guideline-based practice change. CONCLUSIONS: There was a sound
      rationale and clear mechanism for all the components of the intervention but
      issues related to logistics, adaptability and fidelity might have affected
      outcomes. Small group workshops could be a useful implementation strategy in
      community pharmacy, if logistical issues can be overcome and less adaptation
      occurs. Duration, intensity and reinforcement need consideration for successful
      wider implementation. Further qualitative evaluations, triangulation of research
      and evaluations across interventions should be used to provide a greater
      understanding of unresolved issues.

PMID- 27864252
TI  - Predictors of care home and hospital admissions and their costs for older people
      with Alzheimer's disease: findings from a large London case register.
AB  - OBJECTIVES: To examine links between clinical and other characteristics of people
      with Alzheimer's disease living in the community, likelihood of care home or
      hospital admission, and associated costs. DESIGN: Observational data extracted
      from clinical records using natural language processing and Hospital Episode
      Statistics. Statistical analyses examined effects of cognition, physical health,
      mental health, sociodemographic factors and living circumstances on risk of
      admission to care home or hospital over 6 months and associated costs, adjusting
      for repeated observations. SETTING: Catchment area for South London and Maudsley
      National Health Service Foundation Trust, provider for 1.2 million people in
      Southeast London. PARTICIPANTS: Every individual with diagnosis of Alzheimer's
      disease seen and treated by mental health services in the catchment area, with at
      least one rating of cognition, not resident in care home at time of assessment
      (n=3075). INTERVENTIONS: Usual treatment. MAIN OUTCOME MEASURES: Risk of
      admission to, and days spent in three settings during 6-month period following
      routine clinical assessment: care home, mental health inpatient care and general
      hospital inpatient care. RESULTS: Predictors of probability of care home or
      hospital admission and/or associated costs over 6 months include cognition,
      functional problems, agitation, depression, physical illness, previous
      hospitalisations, age, gender, ethnicity, living alone and having a partner.
      Patterns of association differed considerably by destination. CONCLUSIONS: Most
      people with dementia prefer to remain in their own homes, and funding bodies see
      this as cheaper than institutionalisation. Better treatment in the community that
      reduces health and social care needs of Alzheimer's patients would reduce
      admission rates. Living alone, poor living circumstances and functional problems
      all raise admission rates, and so major cuts in social care budgets increase the
      risk of high-cost admissions which older people do not want. Routinely collected
      data can be used to reveal local patterns of admission and costs.

PMID- 27864253
TI  - Macquarie Surgical Innovation Identification Tool (MSIIT): a study protocol for a
      usability and pilot test.
AB  - INTRODUCTION: Medicine relies on innovation to continually improve. However,
      innovation is potentially risky, and not all innovations are successful.
      Therefore, it is important to identify innovations prospectively and provide
      support, to make innovation as safe and effective as possible. The Macquarie
      Surgical Innovation Identification Tool (MSIIT) is a simple checklist designed as
      a practical tool for hospitals to identify planned surgical innovations. This
      project aims to test the usability and pilot the use of the MSIIT in a surgical
      setting. METHODS AND ANALYSIS: The project will run in two phases at two
      Australian hospitals, one public and one private. Phase I will involve
      interviews, focus groups and a survey of hospital administrators and surgical
      teams to assess the usability and system requirements for the use of the MSIIT.
      Current practice regarding surgical innovation within participating hospitals
      will be mapped, and the best implementation strategy for MSIIT completion will be
      established. Phase II will involve trialling the MSIIT for each surgery within
      the trial period by various surgical personnel. Follow-up interviews, focus
      groups and a survey will be conducted with trial participants to collect feedback
      on their experience of using the MSIIT during the trial period. Comparative data
      on rates of surgical innovation during the trial period will also be gathered
      from existing hospital systems and compared to the rates identified by the MSIIT.
      ETHICS AND DISSEMINATION: Ethical approval has been obtained. The results of this
      study will be presented to interested health services and other stakeholders,
      presented at conferences and published in a peer-reviewed MEDLINE-indexed
      journal.

PMID- 27864254
TI  - Physical activity and incident asthma in adults: the HUNT Study, Norway.
AB  - OBJECTIVE: We aimed to investigate the associations of physical activity and
      change in physical activity with incident asthma in a cohort of Norwegian adults.
      DESIGN: We conducted a prospective cohort study using data on self-reported
      physical activity from 3 waves of the Nord-Trondelag Health Study. Physical
      activity was reported at the first and second surveys (1985-1986 and 1995-1997).
      Physical activity was defined from the second survey as inactive or active and
      the active group was further defined as very low, low, moderate and high. Change
      in physical activity was defined from the first and second surveys. SETTING: A
      large population-based health survey in Norway. PARTICIPANTS: We followed 18 894
      adults over 11 years who were free from asthma at baseline in 1995-1997. OUTCOME:
      Incident asthma was reported in the third survey (2006-2008). RESULTS: The
      cumulative incidence of asthma was 3.6% over the 11 years. The adjusted OR for
      incident asthma among active participants compared with inactive participants was
      0.95 (95% CI 0.69 to 1.34). The adjusted OR for those who were active in the
      first or second survey versus those who were inactive in both surveys was 0.64
      (95% CI 0.34 to 1.38); however, this association was strongly attenuated in
      sensitivity analysis (OR 0.93, 95% CI 0.38 to 3.09). CONCLUSIONS: We did not
      observe statistically significant associations of physical activity or change in
      physical activity with incident asthma in adults over the 11-year follow-up.

PMID- 27864256
TI  - UK must act to stem brain drain of scientists, MPs say.

PMID- 27864257
TI  - COPD diagnosis must improve, says report by Royal College of Physicians.

PMID- 27864255
TI  - Improving self-management of cancer risk factors, underscreening for cancer and
      depression among general practice patients: study protocol of a randomised
      controlled trial.
AB  - INTRODUCTION: General practitioners have a key role in reducing cancer risk
      factors, screening for cancer and managing depression. Given the time-limited
      nature of consultations, a new and more time-efficient approach is needed which
      addresses multiple health needs simultaneously, and encourages patient self
      management to address health risks. The aim of this cluster randomised controlled
      trial is to test the effectiveness of a patient feedback intervention in
      improving patient self-management of health needs related to smoking, risky
      alcohol consumption and underscreening for cancers at 1 month follow-up. METHODS
      AND ANALYSIS: Adult general practice patients will be invited to participate in a
      baseline survey to assess cancer risk factors, screening needs and depression. A
      total of 360 participants identified by the baseline survey as having at least
      one health need (a self-reported cancer risk factor, underscreening for cancer,
      or an elevated depression score) will be randomised to an intervention or control
      group. Participants in the intervention group will receive tailored printed
      feedback summarising their identified health needs and recommended self
      management actions to address these. All participants will be invited to complete
      a telephone interview 1 month following recruitment to assess self-management
      actions taken in relation to health needs identified in the baseline survey.
      Control group participants will receive tailored printed feedback on their
      identified health needs after their follow-up interview. A logistic regression
      model, with group allocation as the main predictor, will be used to assess the
      impact of the intervention on self-management actions. ETHICAL CONSIDERATIONS AND
      DISSEMINATION: Participants identified as being at risk of depression will be
      advised to speak with their doctor. Results will be disseminated via publication
      in peer-reviewed journals. The study has been approved by the University of
      Newcastle Human Research Ethics Committee. TRIAL REGISTRATION NUMBER:
      ACTRN12616001443482.

PMID- 27864260
TI  - Light availability affects sex lability in a gynodioecious plant.
AB  - PREMISE OF THE STUDY: Sex lability (i.e., gender diphasy) in plants is
      classically linked to the larger resource needs associated with the female sexual
      function (i.e., seed production) compared to the male function (i.e., pollen
      production). Sex lability in response to the environment is extensively
      documented in dioecious species, but has been largely overlooked in gynodioecious
      plants. METHODS: Here, we tested whether environmental conditions induce sex
      lability in the gynodioecious Geranium sylvaticum. We conducted a transplantation
      experiment in the field where plants with different sex expression were
      reciprocally transplanted between high light and low light habitats. We measured
      plants' reproductive output and sex expression over four years. KEY RESULTS: Our
      results show that sex expression was labile over the study period. The light
      level at the destination habitat had a significant effect on sexual expression
      and reproductive output, because plants decreased their reproductive output when
      transplanted to the low light habitat. Transplantation origin did not affect any
      parameter measured. CONCLUSIONS: This study shows that sex expression in Geranium
      sylvaticum is labile and related to light availability. Sexually labile plants
      did not produce more seeds or pollen, and thus, there was no apparent fitness
      gain in sexually labile individuals. Sex lability in gynodioecious plants may be
      more common than previously believed because detection of sex lability
      necessitates data on the same individuals over time, which is rare in sexually
      dimorphic herbaceous plants.

PMID- 27864261
TI  - Female fruit production depends on female flower production and crown size rather
      than male density in a continuous population of a tropical dioecious tree (Virola
      surinamensis).
AB  - PREMISE OF THE STUDY: Factors related to pollen and resource limitation were
      evaluated to predict female fruit production in a tropical dioecious tree. Pollen
      limitation via variation in the male density at local scales is expected to limit
      female reproduction success in dioecious plants. METHODOLOGY: We modeled the
      roles of local male density, female crown size, crown illumination, and female
      flower production on female fruit initiation and mature fruit production in a
      continuous population (62 ha plot) of a tropical dioecious tree (Virola
      surinamensis). In addition, we used microsatellites to describe the scale of
      effective pollen flow, the male effective population size, and the spatial
      genetic structure within/between progenies and males. KEY RESULTS: The local male
      density was not related to female fruit initiation or mature fruit production.
      Female floral production had a positive effect on fruit initiation. The female
      crown size was positively related to fruit maturation. Seeds from the same female
      and seeds from different but spatially proximal females were generally half
      siblings; however, proximal females showed greater variation. Proximal male
      female adult pairs were not significantly more genetically related than distant
      pairs. The probability of paternity was negatively affected by the distance
      between seeds and males; most effective pollen dispersal events (~85%) occurred
      from males located less than 150 m from females. The number of males siring
      progenies was greater than the number of males found at local scales.
      CONCLUSIONS: Female fecundity in this continuous population of Virola
      surinamensis is not limited by the availability of pollen from proximal males.
      Rather, resource allocation to floral production may ultimately determine female
      reproductive success.

PMID- 27864262
TI  - Interspecific reproductive barriers between sympatric populations of wild tomato
      species (Solanum section Lycopersicon).
AB  - PREMISE OF THE STUDY: Interspecific reproductive barriers (IRBs) often prevent
      hybridization between closely related species in sympatry. In the tomato clade
      (Solanum section Lycopersicon), interspecific interactions between natural
      sympatric populations have not been evaluated previously. In this study, we
      assessed IRBs between members of the tomato clade from nine sympatric sites in
      Peru. METHODS: Coflowering was assessed at sympatric sites in Peru. Using
      previously collected seeds from sympatric sites in Peru, we evaluated premating
      prezygotic (floral morphology), postmating prezygotic (pollen-tube growth), and
      postzygotic barriers (fruit and seed development) between sympatric species in
      common gardens. Pollen-tube growth and seed development were examined in
      reciprocal crosses between sympatric species. KEY RESULTS: We confirmed
      coflowering of sympatric species at five sites in Peru. We found three types of
      postmating prezygotic IRBs during pollen-pistil interactions: (1) unilateral
      pollen-tube rejection between pistils of self-incompatible species and pollen of
      self-compatible species; (2) potential conspecific pollen precedence in a cross
      between two self-incompatible species; and (3) failure of pollen tubes to target
      ovules. In addition, we found strong postzygotic IRBs that prevented normal seed
      development in 11 interspecific crosses, resulting in seed-like structures
      containing globular embryos and aborted endosperm and, in some cases, overgrown
      endothelium. Viable seed and F1 hybrid plants were recovered from three of 19
      interspecific crosses. CONCLUSIONS: We have identified diverse prezygotic and
      postzygotic IRBs that would prevent hybridization between sympatric wild tomato
      species, but interspecific hybridization is possible in a few cases.

PMID- 27864264
TI  - Reproductive success through high pollinator visitation rates despite self
      incompatibility in an endangered wallflower.
AB  - PREMISE OF THE STUDY: Self incompatibility (SI) in rare plants presents a unique
      challenge-SI protects plants from inbreeding depression, but requires a
      sufficient number of mates and xenogamous pollination. Does SI persist in an
      endangered polyploid? Is pollinator visitation sufficient to ensure reproductive
      success? Is there evidence of inbreeding/outbreeding depression? We characterized
      the mating system, primary pollinators, pollen limitation, and
      inbreeding/outbreeding depression in Erysimum teretifolium to guide conservation
      efforts. METHODS: We compared seed production following self pollination and
      within- and between-population crosses. Pollen tubes were visualized after self
      pollinations and between-population pollinations. Pollen limitation was tested in
      the field. Pollinator observations were quantified using digital video.
      Inbreeding/outbreeding depression was assessed in progeny from self and outcross
      pollinations at early and later developmental stages. KEY RESULTS: Self
      pollination reduced seed set by 6.5* and quadrupled reproductive failure compared
      with outcross pollination. Pollen tubes of some self pollinations were arrested
      at the stigmatic surface. Seed-set data indicated strong SI, and fruit-set data
      suggested partial SI. Pollinator diversity and visitation rates were high, and
      there was no evidence of pollen limitation. Inbreeding depression (delta) was
      weak for early developmental stages and strong for later developmental stages,
      with no evidence of outbreeding depression. CONCLUSIONS: The rare hexaploid E.
      teretifolium is largely self incompatible and suffers from late-acting inbreeding
      depression. Reproductive success in natural populations was accomplished through
      high pollinator visitation rates consistent with a lack of pollen limitation.
      Future reproductive health for this species will require large population sizes
      with sufficient mates and a robust pollinator community.

PMID- 27864265
TI  - Systems genetics of plant adaptation to environmental stresses.

PMID- 27864266
TI  - Unusual twig "twistiness" in pawpaw (Asimina triloba) provides biomechanical
      protection for distal foliage in high winds.
AB  - PREMISE OF STUDY: Deciduous woody species invest considerable resources in the
      growth of new foliage and distal stems. This new growth is at risk for mechanical
      damage from high winds and storms. Pawpaw has large leaves borne distally on thin
      twigs. Following a storm, pawpaw branches sometimes exhibit a persistent
      "flipped" orientation, slowly returning upright over 24 h. We investigated
      biomechanical properties of pawpaw twigs, comparing them to co-occurring species
      with similarly high leaf areas and loads, which do not exhibit this "flipping".
      Our goal was to determine biomechanical and structural properties in these
      species and how variation in form might relate to functional differences.
      METHODS: We measured flexural stiffness, torsional stiffness, and viscoelastic
      creep in pawpaw and co-occurring trees Liriodendron tulipifera and Carya
      cordiformis. We also recorded twig/foliage reconfiguration in high winds. We
      stained thin cross sections of distal twigs and recorded images using fluorescent
      light microscopy. KEY RESULTS: Flexural and torsional stiffness increased with
      twig radius in pawpaw and tulip tree, although torsional stiffness increased more
      slowly in pawpaw. Pawpaw had a high ratio of flexural to torsional stiffness
      (EI/GJ) across a range of twig radii and significant viscoelastic creep compared
      with the other species. CONCLUSIONS: Biomechanical data showed that pawpaw twigs
      were "twistier" than the comparison species, which were shown previously to
      alleviate drag-induced damage by reorienting petioles and leaves. Pawpaw has an
      unusual strategy of low torsional stiffness in twigs, allowing for reorientation
      of the entire distal appendage, likely minimizing drag-induced damage in storms.

PMID- 27864267
TI  - Clinical behaviour of spinocerebellar ataxia type 12 and intermediate length
      abnormal CAG repeats in PPP2R2B.
AB  - Spinocerebellar ataxia type 12 (SCA12) is a rare neurodegenerative disorder
      caused by CAG repeat expansion in the PPP2R2B gene. Previously, the causal length
      of CAG repeats ascribed to SCA12 was more than 51; however, a few reports have
      also described unusual occurrence of CAG repeat length 36-51 repeats among
      patients of different geographical population, with atypical clinical
      association. From our systematic search for SCA12 in a genetic screening
      programme, we have identified a large number of SCA12 cases. In this study, we
      specifically describe the clinical behaviour of 18 patients who harbour CAG
      repeats in the range of 43-50 and compare their clinical behaviour with patients
      carrying typical pathogenic threshold length of 51 CAG repeats. Unsurprisingly,
      we observed that the clinical characteristics were similar to those of typical
      SCA12 phenotype, with large variability in the age at onset. Radiologically, we
      observed a variable degree of cerebro-cerebellar degeneration along with white
      matter changes that do not correlate with the disease severity. We define a new
      pathogenic threshold of CAG-43 to be pathogenic for SCA12 diagnosis and also
      describe the clinical profiles of two biallelic CAG expansion carriers. We also
      propose that SCA12 might not be that restricted in terms of occurrence in other
      geographical or ethnic populations, as it was previously presumed to be.

PMID- 27864269
TI  - Reply: In vitro effects of a human monoclonal antibody against the N-methyl-d
      aspartate receptor.

PMID- 27864271
TI  - Fears raised over plan to scale back GP and A&E care in east London.

PMID- 27864268
TI  - De novo GABRG2 mutations associated with epileptic encephalopathies.
AB  - Epileptic encephalopathies are a devastating group of severe childhood onset
      epilepsies with medication-resistant seizures and poor developmental outcomes.
      Many epileptic encephalopathies have a genetic aetiology and are often associated
      with de novo mutations in genes mediating synaptic transmission, including GABAA
      receptor subunit genes. Recently, we performed next generation sequencing on
      patients with a spectrum of epileptic encephalopathy phenotypes, and we
      identified five novel (A106T, I107T, P282S, R323W and F343L) and one known
      (R323Q) de novo GABRG2 pathogenic variants (mutations) in eight patients. To gain
      insight into the molecular basis for how these mutations contribute to epileptic
      encephalopathies, we compared the effects of the mutations on the properties of
      recombinant alpha1beta2gamma2L GABAA receptors transiently expressed in HEK293T
      cells. Using a combination of patch clamp recording, immunoblotting, confocal
      imaging and structural modelling, we characterized the effects of these GABRG2
      mutations on GABAA receptor biogenesis and channel function. Compared with wild
      type alpha1beta2gamma2L receptors, GABAA receptors containing a mutant gamma2
      subunit had reduced cell surface expression with altered subunit stoichiometry or
      decreased GABA-evoked whole-cell current amplitudes, but with different levels of
      reduction. While a causal role of these mutations cannot be established directly
      from these results, the functional analysis together with the genetic information
      suggests that these GABRG2 variants may be major contributors to the epileptic
      encephalopathy phenotypes. Our study further expands the GABRG2 phenotypic
      spectrum and supports growing evidence that defects in GABAergic
      neurotransmission participate in the pathogenesis of genetic epilepsies including
      epileptic encephalopathies.

PMID- 27864270
TI  - In vitro effects of a human monoclonal antibody against the N-methyl-d-aspartate
      receptor.

PMID- 27864273
TI  - Doctors talking to friends and families.

PMID- 27864276
TI  - Death song.

PMID- 27864277
TI  - Molecular characterization of GhPLDalpha1 and its relationship with secondary
      cell wall thickening in cotton fibers.
AB  - Phospholipase D (PLD) hydrolyzes phospholipids to generate a free polar head
      group (e.g., choline) and a second messenger phosphatidic acid and plays diverse
      roles in plant growth and development, including seed germination, leaf
      senescence, root hair growth, and hypocotyl elongation. However, the function of
      PLD in cotton remains largely unexplored. Here, the comprehensive molecular
      characterization of GhPLDalpha1 was explored with its role in upland cotton
      (Gossypium hirsutum) fiber development. The GhPLDalpha1 gene was cloned
      successfully, and a sequence alignment showed that GhPLDalpha1 contains one C2
      domain and two HKD (HxKxxxxD) domains. Quantitative reverse transcriptase
      polymerase chain reaction measured the expression of GhPLDalpha1 in various
      cotton tissues with the highest level in fibers at 20 days post anthesis
      (d.p.a.). Fluorescent microscopy and immunoblotting in tobacco epidermis showed
      the GhPLDalpha1 distribution in both cell membranes and the cytoplasm. An
      activity assay indicated changes in PLDalpha enzyme activity in developing fiber
      cells with a peak level at 20 d.p.a., coinciding with the onset of cellulose
      accumulation and the increased H2O2 content during fiber development.
      Furthermore, the inhibition of PLDalpha activity obviously decreased the
      cellulose and H2O2 contents of in vitro-cultured cotton fibers. These results
      provide important evidence explaining the relationship of GhPLDalpha1 with
      secondary cell wall thickening in cotton fibers in that GhPLDalpha1 may correlate
      with the increased H2O2 content at the onset of secondary cell wall thickening,
      ultimately promoting cellulose biosynthesis.

PMID- 27864279
TI  - Nutrition deficiency promotes apoptosis of cartilage endplate stem cells in a
      caspase-independent manner partially through upregulating BNIP3.
AB  - Nutrition deficiency is reported to induce apoptosis of chondrocytes and
      degeneration of cartilage endplate (CEP) in rabbit. Cartilage endplate stem cells
      (CESCs) are important for the integrity of structure and function of CEP. Bcl
      2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) has been reported to
      regulate apoptosis, autophagy, and cytoprotection. In this study, we aimed to
      determine whether nutrition deficiency induces apoptosis of CESCs, and whether or
      not the BNIP3-related pathway is activated in CESCs during nutrition deficiency.
      CESCs isolated from degenerated human CEP were cultured under normal or nutrition
      deficient condition. Then, apoptosis was analyzed by flow cytometry. The
      expression and intracellular localization of BNIP3 were detected by quantitative
      real-time polymerase chain reaction, western blot analysis, and
      immunofluorescence assay, respectively. Mitochondrial membrane potential (MMP)
      and caspase-3 activity were measured by JC-1 staining and caspase-3 activity
      assay. Our results showed that nutrition deficiency promotes apoptosis and BNIP3
      expression in CESCs. Notably, knockdown of BNIP3 could partially decrease
      nutrition deficiency-induced apoptosis of CESCs. In addition, nutrition
      deficiency could also induce upregulation of BNIP3, resulting in mitochondrial
      translocation of BNIP3 and loss of MMP in CESCs in a time-dependent manner.
      However, nutrition deficiency showed no effects on caspase-3 activity in CESCs.
      In summary, nutrition deficiency may promote CESC apoptosis partially through
      upregulating BNIP3, which might lead to activation of the BNIP3-related pathway
      and apoptosis of CESCs in a caspase-independent manner.

PMID- 27864278
TI  - Integrative analysis for the role of long non-coding RNAs in radiation-induced
      mouse thymocytes responses.
AB  - Long non-coding RNAs (lncRNAs) are a critical class of regulatory molecules
      involved in a variety of biological functions; however, their role in immune
      cells response to radiation is unknown. Therefore, in this study we used
      integrative analysis to determine the expression profile of lncRNAs in mouse
      thymocytes and the potential functions of lncRNAs in response to radiation.
      Microarray data profiling indicated that 53 lncRNAs (36 up-regulated and 17 down
      regulated) and 74 coding genes (39 up-regulated and 35 down-regulated) were
      highly differentially expressed in the high dose radiation (HDR) group compared
      with the control group. In the low dose radiation (LDR) group, only one lncRNA
      was down-regulated. Moreover, as compared with the control group, 109 lncRNA
      pathways in the HDR group and 14 lncRNA pathways in the LDR group were
      differentially expressed. Our data revealed the expression pattern of lncRNAs in
      mouse thymocytes and predicted their potential functions in response to LDR and
      HDR. In the HDR group, GO analysis showed that the role of lncRNAs in damage
      responses of thymocytes to HDR mainly involved chromatin organization and cell
      death. These findings might improve our understanding of the role of lncRNAs in
      LDR- and HDR-induced immune cells and provide a new experimental basis for
      further investigation.

PMID- 27864281
TI  - Lipoprotein lipase and phospholipid transfer protein overexpression in human
      glioma cells and their effect on cell growth, apoptosis, and migration.
AB  - Glioma is one of the common tumors in brain. The expression level of lipoprotein
      lipase (LPL) or phospholipid transfer protein (PLTP) may influence glioma
      progression and its relationship with clinical and pathological parameters. The
      clinical significance of LPL or PLTP expression in glioma has not been
      established. In the present study, the LPL and PLTP levels in glioma tumors were
      investigated and the relationship between the LPL and PLTP level and the grade of
      malignant glioma was analyzed, with the aim to provide new ideas for the
      diagnosis and treatment of gliomas in clinical and basic research settings. LPL
      and PLTP mRNA and protein levels were significantly higher in Grade IV glioma
      than those in the lower grade tumors (P < 0.01). Double immunofluorescent
      staining showed that the levels of LPL and PLTP were significantly associated
      with the pathological grade of glioma (P = 0.005). The levels of LPL and PLTP
      were increased with the shortened survival of glioma patients (P < 0.001).
      Knockdown of LPL and PLTP led to decreased cell growth and migration but
      increased apoptosis in vitro Additionally, cell cycle-related cyclins and their
      partners were found to be down-regulated while cyclin-dependent kinase inhibitors
      p16, p21, and Rb were up-regulated. Furthermore, knockdown of LPL or PLTP
      resulted in the up-regulation of pro-apoptotic molecules and the down-regulation
      of anti-apoptotic molecules. Ablation of LPL or PLTP in U251 cells resulted in
      the down-regulation of epithelial mesenchymal transition markers and invasion
      molecules matrix metalloproteinases. LPL and PLTP appear to be novel glioma
      associated proteins and play a role in the progression of human glioma.

PMID- 27864280
TI  - Edaravone injection reverses learning and memory deficits in a rat model of
      vascular dementia.
AB  - Edaravone is a novel free radical scavenger that exerts neuroprotective effects
      by inhibiting endothelial injury and by ameliorating neuronal damage in brain
      ischemia. Recently, it was reported that edaravone could alleviate the pathology
      and cognitive deficits of Alzheimer's disease patients. However, its relevance to
      vascular dementia (VaD) is not clear. In this study, we partially occluded the
      bilateral carotid arteries of rats surgically to induce chronic cerebral
      hypoperfusion (CCH), a well-known rat model of VaD. Water maze and step-down
      inhibitory test were used to evaluate the memory deficit. The activities of
      superoxide dismutase (SOD) and lactate dehydrogenase (LDH), the content of
      malondialdehyde (MDA) and total reactive oxygen species were measured to evaluate
      the oxidative stress level. Western blot analysis was used to evaluate the
      synaptic protein expression. It was found that treatment with edaravone for a 5
      week period was able to reverse both spatial and fear-memory deficits in rats
      with CCH. Edaravone significantly reduced the level of oxidative stress in the
      brains of rats with CCH by increasing SOD activity and decreasing the content of
      MDA, LDH, and total reactive oxygen species. Furthermore, edaravone treatment
      also restored the levels of multiple synaptic proteins in the hippocampi of rats
      with CCH. Our data provide direct evidence supporting the neuroprotective effects
      of edaravone in VaD. We propose that the alleviation of oxidative stress and
      restoration of synaptic proteins play important roles in neuroprotection.

PMID- 27864282
TI  - Bxb1 integrase serves as a highly efficient DNA recombinase in rapid metabolite
      pathway assembly.
AB  - Phage-encoded serine integrases are widely used in genetic engineering. They also
      have the potential to serve as efficient DNA assemblers, demonstrated by the
      method of site-specific recombination-based tandem assembly (SSRTA) that can
      combine biological parts into devices, pathways, and systems. Here, four serine
      integrases, phiBT1, TG1, phiRv1, and Bxb1, were investigated to ascertain their
      in vitro DNA assembly activities. Bxb1 integrase displayed the highest efficiency
      to obtain final products. Thus, we conclude that Bxb1 integrase is an excellent
      choice for DNA assembly in vitro Using this enzyme and its recognition sites,
      BioBrick standards were designed that are compatible with the SSRTA method for
      module addition. A rapid and efficient procedure was developed for the assembly
      of a multigene metabolic pathway in one step, directly from non-cutting plasmids
      containing the gene fragments. This technique is easy and convenient, and would
      be of interest to the synthetic biology community.

PMID- 27864283
TI  - Tumor necrosis factor-alpha: a key contributor to intervertebral disc
      degeneration.
AB  - Intervertebral disc (IVD) degeneration (IDD) is the most common cause leading to
      low back pain (LBP), which is a highly prevalent, costly, and crippling condition
      worldwide. Current treatments for IDD are limited to treat the symptoms and do
      not target the pathophysiology. Tumor necrosis factor-alpha (TNF-alpha) is one of
      the most potent pro-inflammatory cytokines and signals through its receptors
      TNFR1 and TNFR2. TNF-alpha is highly expressed in degenerative IVD tissues, and
      it is deeply involved in multiple pathological processes of disc degeneration,
      including matrix destruction, inflammatory responses, apoptosis, autophagy, and
      cell proliferation. Importantly, anti-TNF-alpha therapy has shown promise for
      mitigating disc degeneration and relieving LBP. In this review, following a brief
      description of TNF-alpha signal transduction, we mainly focus on the expression
      pattern and roles of TNF-alpha in IDD, and summarize the emerging progress
      regarding its inhibition as a promising biological therapeutic approach to disc
      degeneration and associated LBP. A better understanding will help to develop
      novel TNF-alpha-centered therapeutic interventions for degenerative disc disease.

PMID- 27864285
TI  - IL-23 secreted by bronchial epithelial cells contributes to allergic
      sensitization in asthma model: role of IL-23 secreted by bronchial epithelial
      cells.
AB  - IL-23 has been postulated to be a critical mediator contributing to various
      inflammatory diseases. Dermatophagoides pteronyssinus (Der p) is one of the most
      common inhalant allergens. However, the role of IL-23 in Der p-induced mouse
      asthma model is not well understood, particularly with regard to the development
      of allergic sensitization in the airways. The objective of this study was to
      evaluate roles of IL-23 in Der p sensitization and asthma development. BALB/c
      mice were repeatedly administered Der p intranasally to develop Der p allergic
      sensitization and asthma. After Der p local administration, changes in IL-23
      expression were examined in lung tissues and primary epithelial cells. Anti-IL
      23p19 antibody was given during the Der p sensitization period, and its effects
      were examined. Effects of anti-IL-23p19 antibody at bronchial epithelial levels
      were also examined in vitro. The expression of IL-23 at bronchial epithelial
      layers was increased after Der p local administration in mouse. In Der p-induced
      mouse models, anti-IL-23p19 antibody treatment during allergen sensitization
      significantly diminished Der p allergic sensitization and several features of
      allergic asthma including the production of Th2 cytokines and the population of
      type 2 innate lymphoid cells in lungs. The activation of dendritic cells in lung
      draining lymph nodes was also reduced by anti-IL-23 treatment. In murine lung
      alveolar type II-like epithelial cell line (MLE-12) cells, IL-23 blockade
      prevented cytokine responses to Der p stimulation, such as IL-1alpha, granulocyte
      macrophage colony-stimulating factor (GM-CSF), IL-33, and also bone marrow
      derived dendritic cell activation. In conclusion, IL-23 is another important
      bronchial epithelial cell-driven cytokine which may contribute to the development
      of house dust mite allergic sensitization and asthma.

PMID- 27864284
TI  - Region-specific role for Pten in maintenance of epithelial phenotype and
      integrity.
AB  - Previous studies have demonstrated resistance to naphthalene-induced injury in
      proximal airways of mice with lung epithelial-specific deletion of the tumor
      suppressor gene Pten, attributed to increased proliferation of airway
      progenitors. We tested effects of Pten loss following bleomycin injury, a model
      typically used to study distal lung epithelial injury, in conditional PtenSFTPC
      cre knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia,
      particularly in small bronchioles and at bronchoalveolar duct junctions, with
      reduced E-cadherin and beta-catenin expression between cells toward the luminal
      aspect of the hyperplastic epithelium. Bronchiolar epithelial and alveolar
      epithelial type II (AT2) cells in PtenSFTPC-cre mice showed decreased expression
      of epithelial markers and increased expression of mesenchymal markers, suggesting
      at least partial epithelial-mesenchymal transition at baseline. Surprisingly, and
      in contrast to previous studies, mutant mice were exquisitely sensitive to
      bleomycin, manifesting rapid weight loss, respiratory distress, increased early
      mortality (by day 5), and reduced dynamic lung compliance. This was accompanied
      by sloughing of the hyperplastic airway epithelium with occlusion of small
      bronchioles by cellular debris, without evidence of increased parenchymal lung
      injury. Increased airway epithelial cell apoptosis due to loss of antioxidant
      defenses, reflected by decreased expression of superoxide dismutase 3, in
      combination with deficient intercellular adhesion, likely predisposed to airway
      sloughing in knockout mice. These findings demonstrate an important role for Pten
      in maintenance of airway epithelial phenotype integrity and indicate that
      responses to Pten deletion in respiratory epithelium following acute lung injury
      are highly context-dependent and region-specific.

PMID- 27864287
TI  - Double-hit mouse model of cigarette smoke priming for acute lung injury.
AB  - Epidemiological studies indicate that cigarette smoking (CS) increases the risk
      and severity of acute lung injury (ALI)/acute respiratory distress syndrome
      (ARDS). The mechanism is not understood, at least in part because of lack of
      animal models that reproduce the key features of the CS priming process. In this
      study, using two strains of mice, we characterized a double-hit mouse model of
      ALI induced by CS priming of injury caused by lipopolysaccharide (LPS). C57BL/6
      and AKR mice were preexposed to CS briefly (3 h) or subacutely (3 wk) before
      intratracheal instillation of LPS and ALI was assessed 18 h after LPS
      administration by measuring lung static compliance, lung edema, vascular
      permeability, inflammation, and alveolar apoptosis. We found that as little as 3
      h of exposure to CS enhanced LPS-induced ALI in both strains of mice. Similar
      exacerbating effects were observed after 3 wk of preexposure to CS. However,
      there was a strain difference in susceptibility to CS priming for ALI, with a
      greater effect in AKR mice. The key features we observed suggest that 3 wk of CS
      preexposure of AKR mice is a reproducible, clinically relevant animal model that
      is useful for studying mechanisms and treatment of CS priming for a second-hit
      induced ALI. Our data also support the concept that increased susceptibility to
      ALI/ARDS is an important adverse health consequence of CS exposure that needs to
      be taken into consideration when treating critically ill individuals.

PMID- 27864288
TI  - The role of nuclear factor-erythroid 2 related factor 2 (Nrf-2) in the protection
      against lung injury.
AB  - Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master
      transcription factor that upregulates antioxidant response elements (AREs)
      mediated expression of antioxidant enzyme and cytoprotective proteins. Activation
      of Nrf2 has been shown to be protective against lung injury. In the lung, diverse
      stimuli including environmental oxidants, medicinal agents, and pathogens can
      activate Nrf2. Nrf2 translocates to the nucleus and binds to an ARE. Through
      transcriptional induction of ARE-bearing genes encoding antioxidant-detoxifying
      proteins, Nrf2 induces cellular rescue pathways against oxidative pulmonary
      injury, abnormal inflammatory and immune responses, and apoptosis. The Nrf2
      antioxidant pathway has been shown to be important in the protection against
      various lung injuries including acute lung injury/acute respiratory distress
      syndrome and bronchopulmonary dysplasia, chronic obstructive pulmonary disease,
      idiopathic pulmonary fibrosis, asthma, and allergy and was widely examined for
      new therapeutic targets. The present review explores the protective role of Nrf-2
      against lung injury and the therapeutic potential in targeting Nrf-2.

PMID- 27864286
TI  - Transforming growth factor-beta plays divergent roles in modulating vascular
      remodeling, inflammation, and pulmonary fibrosis in a murine model of
      scleroderma.
AB  - The efficacy and feasibility of targeting transforming growth factor-beta
      (TGFbeta) in pulmonary fibrosis and lung vascular remodeling in systemic
      sclerosis (SSc) have not been well elucidated. In this study we analyzed how
      blocking TGFbeta signaling affects pulmonary abnormalities in Fos-related antigen
      2 (Fra-2) transgenic (Tg) mice, a murine model that manifests three important
      lung pathological features of SSc: fibrosis, inflammation, and vascular
      remodeling. To interrupt TGFbeta signaling in the Fra-2 Tg mice, we used a pan
      TGFbeta-blocking antibody, 1D11, and Tg mice in which TGFbeta receptor type 2
      (Tgfbr2) is deleted from smooth muscle cells and myofibroblasts (alpha-SMA
      CreER;Tgfbr2flox/flox). Global inhibition of TGFbeta by 1D11 did not ameliorate
      lung fibrosis histologically or biochemically, whereas it resulted in a
      significant increase in the number of immune cells infiltrating the lungs. In
      contrast, 1D11 treatment ameliorated the severity of pulmonary vascular
      remodeling in Fra-2 Tg mice. Similarly, genetic deletion of Tgfbr2 from smooth
      muscle cells resulted in improvement of pulmonary vascular remodeling in the Fra
      2 Tg mice, as well as a decrease in the number of Ki67-positive vascular smooth
      muscle cells, suggesting that TGFbeta signaling contributes to development of
      pulmonary vascular remodeling by promoting the proliferation of vascular smooth
      muscle cells. Deletion of Tgfbr2 from alpha-smooth muscle actin-expressing cells
      had no effect on fibrosis or inflammation in this model. These results suggest
      that efforts to target TGFbeta in SSc will likely require more precision than
      simply global inhibition of TGFbeta function.

PMID- 27864289
TI  - Immunotherapy for arterial ischaemic stroke in childhood: a systematic review.
AB  - BACKGROUND: There is little evidence about either prevention or treatment of
      childhood arterial ischaemic stroke (AIS). However, drugs that regulate the
      immune and inflammatory response could theoretically prevent occurrence or
      recurrence of AIS. Additionally, as an acute treatment, they may limit the
      neurological damage caused by AIS. Here, we systematically review the evidence on
      the use of immunotherapy in childhood AIS. DESIGN: A systematic review of
      publications in databases Embase and Medline from inception. All types of
      evidence were included from trials, cohorts, case-control and cross-sectional
      studies and case reports. RESULTS: 34 reports were included: 32 observational
      studies and 2 trials. Immunotherapy was used in two key patient groups:
      arteriopathy and acute infection. The majority were cases of varicella and
      primary angiitis of the central nervous system. All three cohorts and 80% of the
      case studies were treated with steroids. Recurrence rates were low. Analytical
      studies weakly associated steroids with lower odds of new stroke and neurological
      deficits, and better cognitive outcomes in the context of Moyamoya disease and
      tuberculosis. CONCLUSIONS: Immunotherapies are used in children with AIS, mainly
      as steroids for children with arteriopathy. However, there is currently little
      robust evidence to either encourage or discourage this practice. There is weak
      evidence consistent with the hypothesis that in certain children at risk,
      steroids may both reduce the risk of occurrent/recurrent stroke and enhance
      neurological outcomes. As the potential benefit is still uncertain, this
      indicates that a trial of steroids in childhood AIS may be justified.

PMID- 27864290
TI  - Sleep is an important factor when considering rugby union player load.

PMID- 27864291
TI  - Ranald Philip Clayton Handfield-Jones.

PMID- 27864292
TI  - Clinical efficacy of fecal occult blood test and colonoscopy for dasatinib
      induced hemorrhagic colitis in CML patients.

PMID- 27864293
TI  - Expressions of the CagA protein and CagA-signaling molecules predict Helicobacter
      pylori dependence of early-stage gastric DLBCL.
AB  - We previously reported that early-stage gastric diffuse large B-cell lymphomas
      (DLBCLs), including DLBCLs with mucosa-associated lymphoid tissue (DLBCL[MALT])
      and without ("pure" DLBCL) the features of MALT lymphomas, can achieve long-term
      complete remission after frontline Helicobacter pylori (HP) eradication (HPE). We
      recently reported that expression of cytotoxin-associated gene A (CagA) and CagA
      signaling molecules (phospho-Src homology-2 domain-containing phosphatase [p
      SHP2] and phospho-extracellular signal-regulated kinase [p-ERK]) is associated
      with HP dependence of gastric MALT lymphoma. However, the significance of CagA
      and CagA-signaling molecules in gastric DLBCL remains unexplored. The association
      between expression of CagA, p-SHP-2, and p-ERK in malignant B cells and tumor
      response to HPE was evaluated in 63 patients with stage IE/IIE1 HP-positive
      gastric DLBCL who received HPE as frontline treatment. We detected CagA
      expression in 20 of 42 DLBCL (MALT) cases (47.6%) and in 13 of 21 "pure" DLBCL
      cases (61.9%). CagA expression was higher in HP-dependent tumors than in HP
      independent tumors (74.3% [26 of 35] vs 25.0% [7 of 28]). Patients with CagA
      expression responded to HPE quicker than those without expression (median time to
      complete remission, 4.0 months vs 5.0 months). The expression of CagA was closely
      associated with p-SHP-2 and p-ERK expression. Combined CagA, p-SHP-2, and p-ERK
      expression showed an increased positive predictive value (81.8% vs 75.9%) and an
      increased specificity (84.0% vs 75.0%) for HP dependence compared with CagA
      expression alone. Our results indicated that CagA and its signaling molecules can
      be detected in the malignant B cells of gastric DLBCL, and the expression of
      these molecules is clinically and biologically associated with HP dependence.

PMID- 27864297
TI  - Expression of biologically active murine interleukin-18 in Lactococcus lactis.
AB  - The food-grade bacterium Lactococcus lactis is increasingly used for heterologous
      protein expression in therapeutic and industrial applications. The ability of L.
      lactis to secrete biologically active cytokines may be used for the generation of
      therapeutic cytokines. Interleukin (IL)-18 enhances the immune response,
      especially on mucosal surfaces, emphasizing its therapeutic potential. However,
      it is produced as an inactive precursor and has to be enzymatically cleaved for
      maturation. We genetically manipulated L. lactis to secrete murine IL-18. The
      mature murine IL-18 gene was inserted downstream of a nisin promoter in pNZ8149
      plasmid and the construct was used to transform L. lactis NZ3900. The
      transformants were selected on Elliker agar and confirmed by restriction enzyme
      digestion and sequencing. The expression and secretion of IL-18 protein was
      verified by SDS-PAGE, western blotting and ELISA. The biological activity of
      recombinant IL-18 was determined by its ability to induce interferon (IFN)-gamma
      production in L. lactis co-cultured with murine splenic T cells. The amounts of
      IL-18 in bacterial lysates and supernatants were 3-4 MUg mL-1 and 0.6-0.7 ng mL
      1, respectively. The successfully generated L. lactis strain that expressed
      biologically active murine IL-18 can be used to evaluate the possible therapeutic
      effects of IL-18 on mucosal surfaces.

PMID- 27864294
TI  - B-cell receptor-driven MALT1 activity regulates MYC signaling in mantle cell
      lymphoma.
AB  - Mantle cell lymphoma (MCL) is a mature B-cell lymphoma characterized by poor
      clinical outcome. Recent studies revealed the importance of B-cell receptor (BCR)
      signaling in maintaining MCL survival. However, it remains unclear which role
      MALT1, an essential component of the CARD11-BCL10-MALT1 complex that links BCR
      signaling to the NF-kappaB pathway, plays in the biology of MCL. Here we show
      that a subset of MCLs is addicted to MALT1, as its inhibition by either RNA or
      pharmacologic interference induced cytotoxicity both in vitro and in vivo. Gene
      expression profiling following MALT1 inhibition demonstrated that MALT1 controls
      an MYC-driven gene expression network predominantly through increasing MYC
      protein stability. Thus, our analyses identify a previously unappreciated
      regulatory mechanism of MYC expression. Investigating primary mouse splenocytes,
      we could demonstrate that MALT1-induced MYC regulation is not restricted to MCL,
      but represents a common mechanism. MYC itself is pivotal for MCL survival because
      its downregulation and pharmacologic inhibition induced cytotoxicity in all MCL
      models. Collectively, these results provide a strong mechanistic rationale to
      investigate the therapeutic efficacy of targeting the MALT1-MYC axis in MCL
      patients.

PMID- 27864295
TI  - Endothelial cells produce bone morphogenetic protein 6 required for iron
      homeostasis in mice.
AB  - Bone morphogenetic protein 6 (BMP6) signaling in hepatocytes is a central
      transcriptional regulator of the iron hormone hepcidin that controls systemic
      iron balance. How iron levels are sensed to regulate hepcidin production is not
      known, but local induction of liver BMP6 expression by iron is proposed to have a
      critical role. To identify the cellular source of BMP6 responsible for hepcidin
      and iron homeostasis regulation, we generated mice with tissue-specific ablation
      of Bmp6 in different liver cell populations and evaluated their iron phenotype.
      Efficiency and specificity of Cre-mediated recombination was assessed by using
      Cre-reporter mice, polymerase chain reaction of genomic DNA, and quantitation of
      Bmp6 messenger RNA expression from isolated liver cell populations. Localization
      of the BMP co-receptor hemojuvelin was visualized by immunofluorescence
      microscopy. Analysis of the Bmp6 conditional knockout mice revealed that liver
      endothelial cells (ECs) expressed Bmp6, whereas resident liver macrophages
      (Kupffer cells) and hepatocytes did not. Loss of Bmp6 in ECs recapitulated the
      hemochromatosis phenotype of global Bmp6 knockout mice, whereas hepatocyte and
      macrophage Bmp6 conditional knockout mice exhibited no iron phenotype.
      Hemojuvelin was localized on the hepatocyte sinusoidal membrane immediately
      adjacent to Bmp6-producing sinusoidal ECs. Together, these data demonstrate that
      ECs are the predominant source of BMP6 in the liver and support a model in which
      EC BMP6 has paracrine actions on hepatocyte hemojuvelin to regulate hepcidin
      transcription and maintain systemic iron homeostasis.

PMID- 27864298
TI  - N-(3-oxo-hexanoyl)-homoserine lactone has a critical contribution to the quorum
      sensing-dependent regulation in phytopathogen Pseudomonas syringae pv. tabaci
      11528.
AB  - The phytopathogen Pseudomonas syringae pv. tabaci 11528 (P. syringae 11528),
      causing wild-fire disease in soybean and tobacco plants, processes PsyI-PsyR
      quorum-sensing (QS) system, in which PsyI is the N-(3-oxo-hexanoyl)-homoserine
      lactone (3OC6-HSL) synthase. In comparison to P. syringae 11528 AHL-deficient
      mutant, 845 3OC6-HSL-dependent genes were identified using RNA sequencing (RNA
      seq) in the AHL-deficient mutant grown with exogenous 3OC6-HSL in the transition
      from the exponential to the stationary phase, and many of them were associated
      with virulence, which were negatively regulated. The gene ontology and KEGG
      pathway enrichment analysis of those genes presented that the most pronounced
      regulation was involved in bacterial motility. Moreover, similar expression
      profiles of genes during growth phases were observed in both the wild type and
      the AHL-deficient mutant with exogenous 3OC6-HSL compared with the AHL-deficient
      mutant. These findings imply that 3OC6-HSL has a critical contribution to the QS
      dependent regulation on gene expression, and 3OC6-HSL-dependent regulation may
      play a significant role in plant infection.

PMID- 27864299
TI  - Challenges in the use of immunotherapy in metastatic melanoma.
AB  - A 65-year-old man with metastatic melanoma was started on immunotherapy, switched
      to alternative targeted therapy and developed disseminated intravascular
      coagulation. This case underscores the complexity of interpreting and managing
      side effects of novel therapies in cancer care, identification of progression
      versus pseudoprogression and challenges in sequencing treatments in metastatic
      melanoma.

PMID- 27864296
TI  - A mechanistic investigation of thrombotic microangiopathy associated with IV
      abuse of Opana ER.
AB  - Since 2012, a number of case reports have described the occurrence of thrombotic
      microangiopathy (TMA) following IV abuse of extended-release oxymorphone
      hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain.
      Here, we present unique clinical features of 3 patients and investigate IV
      exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea
      pigs were used as an animal model to understand the hematopathologic and
      nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which
      primarily contains high-molecular-weight polyethylene oxide (HMW PEO).
      Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were
      found in a group of 3 patients following recent injection of adulterated extended
      release oxymorphone tablets. Varying degrees of cardiac involvement and retinal
      ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also
      developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal
      injury was accompanied by nonheme iron deposition and hypoxia-inducible factor
      1alpha upregulation in the renal cortex. Similar outcomes were observed following
      dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated
      extended-release oxymorphone can elicit TMA. Although prescription opioid abuse
      shows geographic variation, all physicians should be highly inquisitive of IV
      drug abuse when presented with cases of TMA.

PMID- 27864301
TI  - Bacteraemia due to Parvimonas micra, a commensal pathogen, in a patient with an
      oesophageal tumour.
AB  - A man aged 53 years was admitted to our hospital due to general malaise, fever
      and chills for the past 24 hours. He had a history of chronic alcoholic liver
      disease. The blood tests showed leucocytosis with neutrophilia, lactic acidosis
      and acute-phase reactants. The blood cultures were positive for Parvimonas micra,
      an anaerobic pathogen which is part of the flora of the oral cavity. There was no
      evidence of abscess formation in either the examination or the imaging tests, but
      in the work-up that followed, a gastroscopy showed a stenotic oesophageal mass
      that turned out to be an invasive squamous cell carcinoma.

PMID- 27864300
TI  - Oral and gastrointestinal symptomatic metastases as initial presentation of lung
      cancer.
AB  - Metastasis to the tongue, duodenum or pancreas from primary lung cancer is
      uncommon. Primary lung cancer presenting with symptoms related to metastases at
      these sites, at initial presentation is extremely rare. We report a 45-year-old
      man with disseminated lung malignancy who presented with dyspepsia, melena,
      symptoms due to anaemia and swelling in the tongue. Oral examination revealed a
      hard submucosal anterior tongue lesion. Biopsies from the tongue lesion and the
      duodenal ulcer seen on upper gastrointestinal endoscopy were suggestive of
      metastasis from lung primary. CT revealed lung primary with disseminated
      metastasis to lung, liver, adrenals, kidneys, head and body of pancreas, duodenum
      and intra-abdominal lymph nodes. The patient was treated with palliative
      chemotherapy. The unusual presentation and diagnostic details are discussed.

PMID- 27864302
TI  - Interpregnancy interval following miscarriage and adverse pregnancy outcomes:
      systematic review and meta-analysis.
AB  - BACKGROUND: A short interpregnancy interval (IPI) following a delivery is
      believed to be associated with adverse outcomes in the next pregnancy. The
      optimum IPI following miscarriage is controversial. Based on a single large-scale
      study in Latin and South America, the World Health Organization recommends
      delaying pregnancy for 6 months after a miscarriage to achieve optimal outcomes
      in the next pregnancy. OBJECTIVE AND RATIONALE: Our aim was to determine if a
      short IPI (<6 months) following miscarriage is associated with adverse outcomes
      in the next pregnancy. SEARCH METHODS: Studies were retrieved from MEDLINE,
      Embase and Pubmed, with no time and language restrictions. The search strategy
      used a combination of Medical Subject Headings terms for miscarriage, IPI and
      adverse outcomes. Bibliographies of the retrieved articles were also searched by
      hand. All studies including women with at least one miscarriage, comparing
      subsequent adverse pregnancy outcomes for IPIs of less than and more than 6
      months were included. Two independent reviewers screened titles and abstracts for
      inclusion. Characteristics of the studies were extracted and quality assessed
      using Critical Appraisal Skills Programme criteria. A systematic review and meta
      analysis were conducted to compare short (<6 months) versus long (>6 months) IPI
      following miscarriage in terms of risk of further miscarriage, preterm birth,
      stillbirth, pre-eclampsia and low birthweight babies in the subsequent pregnancy.
      Review Manager 5.3 was used for conducting meta-analyses. OUTCOMES: Sixteen
      studies including 1 043 840 women were included in the systematic review and data
      from 10 of these were included in one or more meta-analyses (977 972 women). With
      an IPI of less than 6 months, the overall risk of further miscarriage (Risk ratio
      (RR) 0.82 95% CI 0.78, 0.86) and preterm delivery (RR 0.79 95% CI 0.75, 0.83)
      were significantly reduced. The pooled risks of stillbirth (RR 0.88 95% CI 0.76,
      1.02); low birthweight (RR 1.05 95% CI 0.48, 2.29) and pre-eclampsia (RR 0.95 95%
      CI 0.88, 1.02) were not affected by IPI. Similar findings were obtained in
      subgroup analyses when IPI of <6 months was compared with IPI of 6-12 months and
      >12 months. WIDER IMPLICATIONS: This is the first systematic review and meta
      analysis providing clear evidence that an IPI of less than 6 months following
      miscarriage is not associated with adverse outcomes in the next pregnancy. This
      information may be used to revise current guidance.

PMID- 27864303
TI  - Diagnosis of Left Ventricular Assist Device Outflow Graft Obstruction Using
      Intravascular Ultrasound.

PMID- 27864304
TI  - Constrictive Pericarditis and Protein-Losing Enteropathy: Is Extremely Severe
      Hypoalbuminemia Reversible by Pericardiectomy?

PMID- 27864306
TI  - The Transactivation Domains of the p53 Protein.
AB  - The p53 tumor suppressor is a transcriptional activator, with discrete domains
      that participate in sequence-specific DNA binding, tetramerization, and
      transcriptional activation. Mutagenesis and reporter studies have delineated two
      distinct activation domains (TADs) and specific hydrophobic residues within these
      TADs that are critical for their function. Knockin mice expressing p53 mutants
      with alterations in either or both of the two TADs have revealed that TAD1 is
      critical for responses to acute DNA damage, whereas both TAD1 and TAD2
      participate in tumor suppression. Biochemical and structural studies have
      identified factors that bind either or both TADs, including general transcription
      factors (GTFs), chromatin modifiers, and negative regulators, helping to
      elaborate a model through which p53 activates transcription. Posttranslational
      modifications (PTMs) of the p53 TADs through phosphorylation also regulate TAD
      activity. Together, these studies on p53 TADs provide great insight into how p53
      serves as a tumor suppressor.

PMID- 27864305
TI  - Oncogenic Mechanisms of Histone H3 Mutations.
AB  - Recurrent missense mutations in histone H3 were recently reported in pediatric
      gliomas and soft tissue tumors. Strikingly, these mutations only affected a
      minority of the total cellular H3 proteins and occurred at or near lysine
      residues at positions 27 and 36 on the amino-terminal tail of H3 that are subject
      to well-characterized posttranslational modifications. Here we review recent
      progress in elucidating the mechanisms by which these mutations perturb the
      chromatin landscape in cells through their effects on chromatin-modifying
      machinery, particularly through inhibition of specific histone lysine
      methyltransferases. One common feature of histone mutations is their ability to
      arrest cells in a primitive state refractory to differentiation induction,
      highlighting the importance of studying these mutations in their proper
      developmental context.

PMID- 27864308
TI  - Working in hot weather: a review of policies and guidelines to minimise the risk
      of harm to Australian workers.

PMID- 27864307
TI  - Pancreatic beta-Cells Express the Fetal Islet Hormone Gastrin in Rodent and Human
      Diabetes.
AB  - beta-Cell failure in type 2 diabetes (T2D) was recently proposed to involve
      dedifferentiation of beta-cells and ectopic expression of other islet hormones,
      including somatostatin and glucagon. Here we show that gastrin, a stomach hormone
      typically expressed in the pancreas only during embryogenesis, is expressed in
      islets of diabetic rodents and humans with T2D. Although gastrin in mice is
      expressed in insulin+ cells, gastrin expression in humans with T2D occurs in both
      insulin+ and somatostatin+ cells. Genetic lineage tracing in mice indicates that
      gastrin expression is turned on in a subset of differentiated beta-cells after
      exposure to severe hyperglycemia. Gastrin expression in adult beta-cells does not
      involve the endocrine progenitor cell regulator neurogenin3 but requires membrane
      depolarization, calcium influx, and calcineurin signaling. In vivo and in vitro
      experiments show that gastrin expression is rapidly eliminated upon exposure of
      beta-cells to normal glucose levels. These results reveal the fetal hormone
      gastrin as a novel marker for reversible human beta-cell reprogramming in
      diabetes.

PMID- 27864309
TI  - Railway suicide clusters: how common are they and what predicts them?
AB  - BACKGROUND: A growing number of studies have sought to detect clusters of all
      suicides, but few have sought to identify clusters of method-specific suicides.
      METHODS: Data on railway suicides occurring in Victoria, Australia, between 2001
      and 2012 were obtained from the National Coronial Information System. We used the
      Poisson discrete scan statistic to identify railway suicides that occurred close
      together in space and/or time. We then used a case-control design to compare
      clustered railway suicides with non-clustered railway suicides on a range of
      individual and neighbourhood factors. RESULTS: We detected four spatial clusters
      that accounted for 35% of all railway suicides. Railway suicides by individuals
      who were hospitalised for mental illness had nearly double the odds of being in a
      cluster compared with those individuals who had never been hospitalised (OR 1.80,
      95% CI 1.02 to 3.18). Higher frequency train services were associated with
      increased odds of being in a cluster (OR 1.11, 95% CI 1.03 to 1.19). No other
      predictors were associated with being in a cluster. CONCLUSIONS: Railway suicides
      that occur in clusters warrant particular attention because of the ripple effect
      they can have for communities and the risk that they may lead to copycat acts.
      Railway suicide prevention strategies should consider the fact that these
      suicides can occur in clusters, particularly among individuals who had previous
      hospitalisations for mental illness or live in areas with high-frequency train
      services.

PMID- 27864311
TI  - Late Dehiscence of Left Atrial Appendage Closure Device.

PMID- 27864312
TI  - Atrial Pathology Findings in a Patient With PRKAG2 Cardiomyopathy and Persistent
      Atrial Fibrillation.

PMID- 27864310
TI  - Low TLR7 gene expression in atherosclerotic plaques is associated with major
      adverse cardio- and cerebrovascular events.
AB  - AIMS: Processes in the development of atherosclerotic lesions can lead to plaque
      rupture or erosion, which can in turn elicit myocardial infarction or ischaemic
      stroke. The aims of this study were to determine whether Toll-like receptor 7
      (TLR7) gene expression levels influence patient outcome and to explore the
      mechanisms linked to TLR7 expression in atherosclerosis. METHODS AND RESULTS:
      Atherosclerotic plaques were removed by carotid endarterectomy (CEA) and
      subjected to gene array expression analysis (n = 123). Increased levels of TLR7
      transcript in the plaques were associated with better outcome in a follow-up
      study over a maximum of 8 years. Patients with higher TLR7 transcript levels had
      a lower risk of experiencing major cardiovascular and cerebrovascular events
      (MACCE) during the follow-up period after CEA (hazard ratio: 2.38, P = 0.012, 95%
      CI 1.21-4.67). TLR7 was expressed in all plaques by T cells, macrophages and
      endothelial cells in capillaries, as shown by immunohistochemistry. In short-term
      tissue cultures, ex vivo treatment of plaques with the TLR7 ligand imiquimod
      elicited dose-dependent secretion of IL-10, TNF-alpha, GM-CSF, and IL-12/IL
      23p40. This secretion was blocked with a TLR7 inhibitor. Immunofluorescent tissue
      analysis after TLR7 stimulation showed IL-10 expression in T cells, macrophages
      and vascular smooth muscle cells. TLR7 mRNA levels in the plaques were correlated
      with IL-10 receptor (r = 0.4031, P < 0.0001) and GM-CSF receptor A (r = 0.4354, P
      < 0.0001) transcripts. CONCLUSION: These findings demonstrate that TLR7 is
      abundantly expressed in human atherosclerotic plaques. TLR7 ligation elicits the
      secretion of pro-inflammatory and anti-inflammatory cytokines, and high TLR7
      expression in plaques is associated with better patient outcome, suggesting that
      TLR7 is a potential therapeutic target for prevention of complications of
      atherosclerosis.

PMID- 27864313
TI  - Non-Smad Signaling Pathways of the TGF-beta Family.
AB  - Transforming growth factor beta (TGF-beta) and structurally related factors use
      several intracellular signaling pathways in addition to Smad signaling to
      regulate a wide array of cellular functions. These non-Smad signaling pathways
      are activated directly by ligand-occupied receptors to reinforce, attenuate, or
      otherwise modulate downstream cellular responses. This review summarizes the
      current knowledge of the mechanisms by which non-Smad signaling pathways are
      directly activated in response to ligand binding, how activation of these
      pathways impinges on Smads and non-Smad targets, and how final cellular responses
      are affected in response to these noncanonical signaling modes.

PMID- 27864315
TI  - Protein Quality Control in Health and Disease.
AB  - Maintaining functional protein homeostasis (proteostasis) is a constant challenge
      in the face of limited protein-folding capacity, environmental threats, and
      aging. Cells have developed several quality-control mechanisms that assist
      nascent polypeptides to fold properly, clear misfolded molecules, respond to the
      accumulation of protein aggregates, and deposit potentially toxic conformers in
      designated sites. Proteostasis collapse can lead to the development of diseases
      known as proteinopathies. Here we delineate the current knowledge on the
      different layers of protein quality-control mechanisms at the organelle and
      cellular levels with an emphasis on the prion protein (PrP). We also describe how
      protein quality control is integrated at the organismal level and discuss future
      perspectives on utilizing proteostasis maintenance as a strategy to develop novel
      therapies for the treatment of proteinopathies.

PMID- 27864314
TI  - Cilia and Mucociliary Clearance.
AB  - Mucociliary clearance (MCC) is the primary innate defense mechanism of the lung.
      The functional components are the protective mucous layer, the airway surface
      liquid layer, and the cilia on the surface of ciliated cells. The cilia are
      specialized organelles that beat in metachronal waves to propel pathogens and
      inhaled particles trapped in the mucous layer out of the airways. In health this
      clearance mechanism is effective, but in patients with primary cilia dyskinesia
      (PCD) the cilia are abnormal, resulting in deficient MCC and chronic lung
      disease. This demonstrates the critical importance of the cilia for human health.
      In this review, we summarize the current knowledge of the components of the MCC
      apparatus, focusing on the role of cilia in MCC.

PMID- 27864317
TI  - Prednisolone is associated with a worse lipid profile than hydrocortisone in
      patients with adrenal insufficiency.
AB  - OBJECTIVE: Prednisolone is used as glucocorticoid replacement therapy for adrenal
      insufficiency (AI). Recent data indicate that its use in AI is associated with
      low bone mineral density. Data on risk factors for cardiovascular disease in
      patients with AI treated with prednisolone are scarce, despite this condition
      being the predominant cause of excess mortality. We aimed to address this
      question using real-world data from the European Adrenal Insufficiency Registry
      (EU-AIR). DESIGN/METHODS: EU-AIR, comprising of 19 centres across Germany, the
      Netherlands, Sweden and the UK, commenced enrolling patients with AI in August
      2012. Patients receiving prednisolone (3-6 mg/day, n = 50) or hydrocortisone (15
      30 mg/day, n = 909) were identified and grouped at a ratio of 1:3
      (prednisolone:hydrocortisone) by matching for gender, age, duration and type of
      disease. Data from baseline and follow-up visits were analysed. Data from
      patients with congenital adrenal hyperplasia were excluded. RESULTS:
      Significantly higher mean +/- s.d. total (6.3 +/- 1.6 vs 5.4 +/- 1.1 mmol/L; P =
      0.003) and low-density lipoprotein (LDL) cholesterol levels (3.9 +/- 1.4 vs 3.2
      +/- 1.0 mmol/L; P = 0.013) were identified in 47 patients on prednisolone vs 141
      receiving hydrocortisone at baseline and at follow-up (P = 0.005 and P = 0.006,
      respectively). HbA1c, high-density lipoprotein and triglyceride levels, body mass
      index, systolic and diastolic blood pressure and waist circumference were not
      significantly different. CONCLUSIONS: This is the first matched analysis of its
      kind. Significantly higher LDL levels in patients receiving prednisolone relative
      to hydrocortisone could predict a higher relative risk of cardiovascular disease
      in the former group.

PMID- 27864319
TI  - Structured telephone support or non-invasive telemonitoring for patients with
      heart failure.

PMID- 27864318
TI  - Coronary heart disease and risk factors as predictors of trajectories of
      psychological distress from midlife to old age.
AB  - OBJECTIVE: To examine coronary heart disease (CHD) and its risk factors as
      predictors of long-term trajectories of psychological distress from midlife to
      old age. METHODS: In the Whitehall II cohort study, 6890 participants (4814 men,
      2076 women; mean age 49.5 years) had up to seven repeat assessments of
      psychological distress over 21 years (mean follow-up 19 years). CHD and its risk
      factors (lifestyle-related risk factors, diabetes, hypertension and cholesterol)
      were assessed at baseline. Group-based trajectory modelling was used to identify
      clusters of individuals with a similar pattern of psychological distress over
      time. RESULTS: We identified four trajectories of psychological distress over the
      follow-up: 'persistently low' (69% of the participants), 'persistently
      intermediate' (13%), 'intermediate to low' (12%) and 'persistently high' (7%).
      The corresponding proportions were 60%, 16%, 13% and 11% among participants with
      CHD; 63%, 15%, 12% and 10% among smokers and 63%, 16%, 12% and 10% among obese
      participants. In multivariable adjusted multinomial regression analyses comparing
      other trajectories to persistently low trajectory, prevalent CHD was associated
      with intermediate to low (OR 1.70, 95% CI 1.08 to 2.68) and persistently high (OR
      1.92, 95% CI 1.16 to 3.19) trajectories. Smoking (OR 1.33, 95% CI 1.07 to 1.64;
      OR 1.55, 95% CI 1.19 to 2.04) and obesity (OR 1.33, 95% CI 1.04 to 1.70; OR 1.47,
      95% CI 1.07 to 2.01) were associated with persistently intermediate and
      persistently high trajectories, respectively. CONCLUSION: CHD, smoking and
      obesity may have a role in the development of long-lasting psychological distress
      from midlife to old age.

PMID- 27864320
TI  - Three questionnaires to assess the perception of fixed orthodontic therapy
      before, during and after treatment: validity and reliability.
AB  - Background/objective: To assess the validity and reliability of a series of three
      questionnaires for the quantification of patient perception of fixed appliance
      orthodontic treatment. Subjects and methods: The study was carried out at the
      University of Dundee with content and face validity being assessed using
      proformas. Initially ten experts (Orthodontic Specialists) assessed content
      validity with 11 professionals (seven Orthodontic Specialists and four
      Postgraduates) and 20 patients assessing face validity. Content validity was
      determined according to the values of item-level content validity index (I-CVI)
      and scale-level CVI (S-CVI/Ave), while specially designed feedback forms were
      used for face validation. Internal consistency determined the reliability of the
      questionnaires according to the value of Cronbach alpha correlation coefficient
      test. The three questionnaires were then modified according to the
      recommendations of professionals and patients with seven experts reassessing
      content validity and ten newly selected patients assessing face validity.
      Results: The first round of content validity revealed that around half of the
      items in the questionnaires were not valid. Therefore, the questionnaires were
      not valid as a whole (S-CVI/Ave = 0.60). After modifying the questionnaires and
      removing the non-valid items, the new versions of the Pre-treatment, Orthodontic
      Experience, and Post-treatment Questionnaires showed high levels of face
      validity, content validity (S-CVI/Ave: 0.99, 0.97, and 0.99, respectively) and
      good levels of internal consistency (alpha = 0.86, 0.78, and 0.88, respectively).
      Limitation: The patient sample was collected from a single university clinic and
      from one city within the UK and this could affect the generalizability of the
      results. Conclusion: Three content valid and reliable questionnaires have been
      developed and validated for the evaluation of patient perception of fixed
      appliance orthodontic treatment. Implications: Unlike other tools that assess
      oral health-related quality of life, this series of three questionnaires assess
      the perception of fixed appliance orthodontic treatment before, during and after
      treatment.

PMID- 27864321
TI  - Atg8 family LC3/GABARAP proteins are crucial for autophagosome-lysosome fusion
      but not autophagosome formation during PINK1/Parkin mitophagy and starvation.
AB  - Members of the Atg8 family of proteins are conjugated to autophagosomal
      membranes, where they have been proposed to drive autophagosome formation and
      selective sequestration of cargo. In mammals, the Atg8 family consists of six
      members divided into the LC3 and GABARAP subfamilies. To define Atg8 function, we
      used genome editing to generate knockouts of the LC3 and GABARAP subfamilies as
      well as all six Atg8 family members in HeLa cells. We show that Atg8s are
      dispensable for autophagosome formation and selective engulfment of mitochondria,
      but essential for autophagosome-lysosome fusion. We find that the GABARAP
      subfamily promotes PLEKHM1 recruitment and governs autophagosome-lysosome fusion,
      whereas the LC3 subfamily plays a less prominent role in these processes.
      Although neither GABARAPs nor LC3s are required for autophagosome biogenesis,
      loss of all Atg8s yields smaller autophagosomes and a slowed initial rate of
      autophagosome formation. Our results clarify the essential function of the Atg8
      family and identify GABARAP subfamily members as primary contributors to
      PINK1/Parkin mitophagy and starvation autophagy.

PMID- 27864323
TI  - What is policy and where do we look for it when we want to research it?
AB  - Public health researchers are increasingly concerned with achieving 'upstream'
      change to achieve reductions in the global burden of disease and health
      inequalities. Consequently, understanding policy and how to change it has become
      a central goal of public health. Yet conceptualisation of what constitutes policy
      and where it can be found is very limited within this field. Our glossary
      demonstrates that policy is many headed. It is located in a vast array of
      documents, discussions dialogues and actions which can be captured variously by
      formal and informal forms of documentation and observation. Effectively
      understanding policy and its relevance for public health requires an awareness of
      the full range of places and contexts in which policy work happens and policy
      documents are produced.

PMID- 27864322
TI  - Escherichia coli Proteome Microarrays Identified the Substrates of ClpYQ
      Protease.
AB  - Proteolysis is a vital mechanism to regulate the cellular proteome in all
      kingdoms of life, and ATP-dependent proteases play a crucial role within this
      process. In Escherichia coli, ClpYQ is one of the primary ATP-dependent
      proteases. In addition to function with removals of abnormal peptides in the
      cells, ClpYQ degrades regulatory proteins if necessary and thus let cells adjust
      to various environmental conditions. In E. coli, SulA, RcsA, RpoH and TraJ as
      well as RNase R, have been identified as natural protein substrates of ClpYQ.
      ClpYQ contains ClpY and ClpQ. The ATPase ClpY is responsible for protein
      recognition, unfolding, and translocation into the catalytic core of ClpQ. In
      this study, we use an indirect identification strategy to screen possible ClpY
      targets with E. coli K12 proteome chips. The chip assay results showed that YbaB
      strongly bound to ClpY. We used yeast two-hybrid assay to confirm the
      interactions between ClpY and YbaB protein and determined the Kd between ClpY and
      YbaB by quartz crystal microbalance. Furthermore, we validated that YbaB was
      successfully degraded by ClpYQ protease activity using ClpYQ in vitro and in vivo
      degradation assay. These findings demonstrated the YbaB is a novel substrate of
      ClpYQ protease. This work also successfully demonstrated that with the use of
      recognition element of a protease can successfully screen its substrates by
      indirect proteome chip screening assay.

PMID- 27864324
TI  - Colorectal cancer is a leading cause of cancer incidence and mortality among
      adults younger than 50 years in the USA: a SEER-based analysis with comparison to
      other young-onset cancers.
AB  - Colorectal cancer (CRC) incidence and mortality are rising among young adults.
      Our aim was to contrast the relative incidence and mortality of CRC to other
      common cancers among young adults in the USA. We used Surveillance, Epidemiology,
      and End Results registry data to compare cancer site-specific and age-specific
      mortality and incident rates for adults younger than age 50. We summarized
      extracted data, both overall, and stratified by sex. We found CRC was the third
      leading cause of cancer death among adults younger than age 50, after breast and
      lung cancer (1.67 cases per 100,000). Among young women, CRC was the fourth
      leading cause of cancer death (1.51 per 100,000). Among young men, CRC was the
      second leading cause of cancer death (1.82 cases per 100,000). CRC was the second
      most incident cancer among young adults for men and women combined. Among men,
      CRC was the second most incident cancer after age 30, with 4.9, 9.0, 16.4, and
      30.8 cases per 100,000 for ages 30-34, 35-39, 40-44, and 45-49 years,
      respectively. Among women, CRC incidence was similar with 4.2, 7.6, 15.3, and
      25.9 cases per 100,000 for ages 30-34, 35-39, 40-44, and 45-49 years,
      respectively. These results show that CRC is a leading cause of cancer incidence
      and mortality among young adults in the USA, relative to other cancers. Given
      trends toward increasing rates of CRC among young adults, strategies for
      identifying individuals at risk for young-onset CRC who might benefit from early
      age of screening initiation merit investigation.

PMID- 27864325
TI  - A technical consideration when using flow diversion for recurrent aneurysms
      following stent-assisted coiling.
AB  - Flow diversion (FD) is a treatment option for recurrent aneurysms including
      following stent-assisted coiling (SAC), although this approach is both 'off
      label' and unproven. A technical challenge of FD placement may involve the
      microwire catching on the tines of the previously placed stent or potentially
      going 'in-out-in' from the central axis of the stent. We report a case and
      technique that assures the wire has safely remained within the central axis of
      the stent. The procedure was performed in standard fashion except that the
      intermediate catheter was passed completely through the previously placed stent
      after the microwire/microcatheter had crossed. The large diameter of the
      intermediate catheter assured that the microwire did not go 'in-out-in'. The
      intermediate catheter was completely withdrawn from the stent and the FD was
      placed in standard fashion. This technique may help to achieve complete FD
      opening and prevent thromboembolic complications associated with incomplete FD
      opening.

PMID- 27864327
TI  - Erratum.

PMID- 27864326
TI  - Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in
      perinatal mice.
AB  - The molecular details relevant to dietary supplementation of the omega-3 fatty
      acid DHA in mothers as well as in their offspring are not clear. The PUFA
      elongase, elongation of very long-chain fatty acid (ELOVL)2, is a critical enzyme
      in the formation of DHA in mammals. In order to address the question regarding
      the origin of DHA during perinatal life, we have used DHA-deficient Elovl2
      ablated mice as a model system to analyze the maternal impact on the DHA level in
      their offspring of various genotypes. Elovl2-/- mothers maintained on control
      diet had significantly lower systemic levels of DHA compared with the Elovl2+/-
      and Elovl2+/+ mothers. Dietary DHA administration during the pregnancy and
      lactation periods led to increased DHA accretion in maternal tissues and serum of
      all genotypes. The proportion of DHA in the liver and serum of the Elovl2-/-
      offspring was significantly lower than in the Elovl2+/+ offspring. Remarkably,
      the DHA level in the Elovl2+/- offspring nursed by DHA-free-fed Elovl2-/- mothers
      was almost as high as in +/+ pups delivered by +/+ mothers, suggesting that
      endogenous synthesis in the offspring can compensate for maternal DHA deficiency.
      Maternal DHA supplementation had a strong impact on offspring hepatic gene
      expression, especially of the fatty acid transporter, Mfsd2a, suggesting a
      dynamic interplay between DHA synthesis and DHA uptake in the control of systemic
      levels in the offspring.

PMID- 27864330
TI  - Three-dimensional stochastic model of actin-myosin binding in the sarcomere
      lattice.
AB  - The effect of molecule tethering in three-dimensional (3-D) space on bimolecular
      binding kinetics is rarely addressed and only occasionally incorporated into
      models of cell motility. The simplest system that can quantitatively determine
      this effect is the 3-D sarcomere lattice of the striated muscle, where tethered
      myosin in thick filaments can only bind to a relatively small number of available
      sites on the actin filament, positioned within a limited range of thermal
      movement of the myosin head. Here we implement spatially explicit actomyosin
      interactions into the multiscale Monte Carlo platform MUSICO, specifically
      defining how geometrical constraints on tethered myosins can modulate state
      transition rates in the actomyosin cycle. The simulations provide the
      distribution of myosin bound to sites on actin, ensure conservation of the number
      of interacting myosins and actin monomers, and most importantly, the departure in
      behavior of tethered myosin molecules from unconstrained myosin interactions with
      actin. In addition, MUSICO determines the number of cross-bridges in each
      actomyosin cycle state, the force and number of attached cross-bridges per myosin
      filament, the range of cross-bridge forces and accounts for energy consumption.
      At the macroscopic scale, MUSICO simulations show large differences in predicted
      force-velocity curves and in the response during early force recovery phase after
      a step change in length comparing to the two simplest mass action kinetic models.
      The origin of these differences is rooted in the different fluxes of myosin
      binding and corresponding instantaneous cross-bridge distributions and
      quantitatively reflects a major flaw of the mathematical description in all mass
      action kinetic models. Consequently, this new approach shows that accurate
      recapitulation of experimental data requires significantly different binding
      rates, number of actomyosin states, and cross-bridge elasticity than typically
      used in mass action kinetic models to correctly describe the biochemical
      reactions of tethered molecules and their interaction energetics.

PMID- 27864332
TI  - Weak silica nanomaterial-induced genotoxicity can be explained by indirect DNA
      damage as shown by the OGG1-modified comet assay and genomic analysis.
AB  - In a previous study, 15-nm silica nanoparticles (NPs) caused small increases in
      DNA damage in liver as measured in the in vivo comet and micronucleus assays
      after intravenous administration to rats at their maximum tolerated dose, a worst
      case exposure scenario. Histopathological examination supported a particle
      induced, tissue damage-mediated inflammatory response. This study used a targeted
      approach to provide insight into the mode of action (MoA) by examining
      transcriptional regulation of genes in liver in a time and dose-dependent manner
      at 1, 2, 4, 8 and 24 h after intravenous administration of 15-nm silica NPs. DNA
      damage was assessed using the standard comet assay and hOGG1 glycosylase-modified
      comet assay that also measures oxidative DNA damage. Potassium bromate, an IARC
      Class 2B carcinogen that specifically operates via an oxidative stress MoA, was
      used as a positive control for the hOGG1 comet assay and gave a strong signal in
      its main target organ, the kidney, while showing less activity in liver.
      Treatment of rats with silica NPs at 50 mg/kg body weight (bw) caused small,
      statistically insignificant increases in DNA damage in liver measured by the
      standard comet assay, while a statistically significant increase was observed at
      4 h with the hOGG1 comet assay, consistent with a MoA involving reactive oxygen
      species. Histopathology showed liver damage and neutrophil involvement while
      genomic analysis and response pattern of key genes involved in inflammation and
      oxidative stress supported a tissue damage-mediated inflammatory response
      involving the complement system for removing/phagocytising damaged cells. No
      changes were observed for histopathology or gene array for the low-dose (5 mg/kg
      bw) silica NPs. The results of this study confirm our hypothesis that the weak
      DNA damage observed by silica NPs occurs secondary to inflammation/immune
      response, indicating that a threshold can be applied in the risk assessment of
      these materials.

PMID- 27864331
TI  - Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated
      Lamellipodia Formation in Lung Endothelium.
AB  - Hepatocyte growth factor (HGF) signaling via c-Met is known to promote
      endothelial cell motility and angiogenesis. We have previously reported that HGF
      stimulates lamellipodia formation and motility of human lung microvascular
      endothelial cells (HLMVECs) via PI3K/Akt signal transduction and reactive oxygen
      species generation. Here, we report a role for HGF-induced intracellular
      sphingosine-1-phosphate (S1P) generation catalyzed by sphingosine kinase 1
      (SphK1), S1P transporter, spinster homolog 2 (Spns2), and S1P receptor, S1P1, in
      lamellipodia formation and perhaps motility of HLMVECs. HGF stimulated SphK1
      phosphorylation and enhanced intracellular S1P levels in HLMVECs, which was
      blocked by inhibition of SphK1. HGF enhanced co-localization of SphK1/p-SphK1
      with actin/cortactin in lamellipodia and down-regulation or inhibition of SphK1
      attenuated HGF-induced lamellipodia formation in HLMVECs. In addition, down
      regulation of Spns2 also suppressed HGF-induced lamellipodia formation,
      suggesting a key role for inside-out S1P signaling. The HGF-mediated
      phosphorylation of SphK1 and its localization in lamellipodia was dependent on c
      Met and ERK1/2 signaling, but not the PI3K/Akt pathway; however, blocking
      PI3K/Akt signaling attenuated HGF-mediated phosphorylation of Spns2. Down
      regulation of S1P1, but not S1P2 or S1P3, with specific siRNA attenuated HGF
      induced lamellipodia formation. Further, HGF enhanced association of Spns2 with
      S1P1 that was blocked by inhibiting SphK1 activity with PF-543. Moreover, HGF
      induced migration of HLMVECs was attenuated by down-regulation of Spns2. Taken
      together, these results suggest that HGF/c-Met-mediated lamellipodia formation,
      and perhaps motility is dependent on intracellular generation of S1P via
      activation and localization of SphK1 to cell periphery and Spns2-mediated
      extracellular transportation of S1P and its inside-out signaling via S1P1.

PMID- 27864334
TI  - Deubiquitinase OTUD6B Isoforms Are Important Regulators of Growth and
      Proliferation.
AB  - : Deubiquitinases (DUB) are increasingly linked to the regulation of fundamental
      processes in normal and cancer cells, including DNA replication and repair,
      programmed cell death, and oncogenes and tumor suppressor signaling. Here,
      evidence is presented that the deubiquitinase OTUD6B regulates protein synthesis
      in non-small cell lung cancer (NSCLC) cells, operating downstream from mTORC1.
      OTUD6B associates with the protein synthesis initiation complex and modifies
      components of the 48S preinitiation complex. The two main OTUD6B splicing
      isoforms seem to regulate protein synthesis in opposing fashions: the long OTUD6B
      1 isoform is inhibitory, while the short OTUD6B-2 isoform stimulates protein
      synthesis. These properties affect NSCLC cell proliferation, because OTUD6B-1
      represses DNA synthesis while OTUD6B-2 promotes it. Mutational analysis and
      downstream mediators suggest that the two OTUD6B isoforms modify different
      cellular targets. OTUD6B-2 influences the expression of cyclin D1 by promoting
      its translation while regulating (directly or indirectly) c-Myc protein
      stability. This phenomenon appears to have clinical relevance as NSCLC cells and
      human tumor specimens have a reduced OTUD6B-1/OTUD6B-2 mRNA ratio compared with
      normal samples. The global OTUD6B expression level does not change significantly
      between nonneoplastic and malignant tissues, suggesting that modifications of
      splicing factors during the process of transformation are responsible for this
      isoform switch. IMPLICATIONS: Because protein synthesis inhibition is a viable
      treatment strategy for NSCLC, these data indicate that OTUD6B isoform 2, being
      specifically linked to NSCLC growth, represents an attractive, novel therapeutic
      target and potential biomarker for early diagnosis of malignant NSCLC. Mol Cancer
      Res; 15(2); 117-27. (c)2016 AACR.

PMID- 27864338
TI  - Ertapenem and Valproic Acid Drug Interaction in an Adult Status Epilepticus
      Patient.

PMID- 27864339
TI  - Development of a Platform to Enable Fully Automated Cross-Titration Experiments.
AB  - In the triage of hits from a high-throughput screening campaign or during the
      optimization of a lead compound, it is relatively routine to test compounds at
      multiple concentrations to determine potency and maximal effect. Additional
      follow-up experiments, such as agonist shift, can be quite valuable in
      ascertaining compound mechanism of action (MOA). However, these experiments
      require cross-titration of a test compound with the activating ligand of the
      receptor requiring 100-200 data points, severely limiting the number tested in
      MOA assays in a screening triage. We describe a process to enhance the throughput
      of such cross-titration experiments through the integration of Hewlett Packard's
      D300 digital dispenser onto one of our robotics platforms to enable on-the-fly
      cross-titration of compounds in a 1536-well plate format. The process handles all
      the compound management and data tracking, as well as the biological assay. The
      process relies heavily on in-house-built software and hardware, and uses our
      proprietary control software for the platform. Using this system, we were able to
      automate the cross-titration of compounds for both positive and negative
      allosteric modulators of two different G protein-coupled receptors (GPCRs) using
      two distinct assay detection formats, IP1 and Ca2+ detection, on nearly 100
      compounds for each target.

PMID- 27864336
TI  - BMP4 promotes mouse iPS cell differentiation to male germ cells via Smad1/5,
      Gata4, Id1 and Id2.
AB  - Generation of male germ cells from pluripotent cells could provide male gametes
      for treating male infertility and offer an ideal model for unveiling molecular
      mechanisms of spermatogenesis. However, the influence and exact molecular
      mechanisms, especially downstream effectors of BMP4 signaling pathways, in male
      germ cell differentiation of the induce pluripotent stem (iPS) cells, remain
      unknown. This study was designed to explore the role and mechanism of BMP4
      signaling in the differentiation of mouse iPS cells to male germ cells. Embryoid
      body (EB) formation and recombinant BMP4 or Noggin were utilized to evaluate the
      effect of BMP4 on male germ cell generation from mouse iPS cells. Germ cell
      specific genes and proteins as well as the downstream effectors of BMP4 signaling
      pathway were assessed using real-time PCR and Western blots. We found that BMP4
      ligand and its multiple receptors, including BMPR1a, BMPR1b and BMPR2, were
      expressed in mouse iPS cells. Real-time PCR and Western blots revealed that BMP4
      could upregulate the levels of genes and proteins for germ cell markers in iPS
      cells-derived EBs, whereas Noggin decreased their expression in these cells.
      Moreover, Smad1/5 phosphorylation, Gata4 transcription and the transcripts of Id1
      and Id2 were enhanced by BMP4 but decreased when exposed to Noggin. Collectively,
      these results suggest that BMP4 promotes the generation of male germ cells from
      iPS cells via Smad1/5 pathway and the activation of Gata4, Id1 and Id2 This study
      thus offers novel insights into molecular mechanisms underlying male germ cell
      development.

PMID- 27864335
TI  - Effects of maternal obesity on placental function and fetal development.
AB  - Obesity has reached epidemic proportions, and pregnancies in obese mothers have
      increased risk for complications including gestational diabetes, hypertensive
      disorders, pre-term birth and caesarian section. Children born to obese mothers
      are at increased risk of obesity and metabolic disease and are susceptible to
      develop neuropsychiatric and cognitive disorders. Changes in placental function
      not only play a critical role in the development of pregnancy complications but
      may also be involved in linking maternal obesity to long-term health risks in the
      infant. Maternal adipokines, i.e., interleukin 6 (IL-6), tumor necrosis factor
      alpha (TNF-alpha), leptin and adiponectin link maternal nutritional status and
      adipose tissue metabolism to placental function. Adipokines and metabolic
      hormones have direct impact on placental function by modulating placental
      nutrient transport. Nutrient delivery to the fetus is regulated by a complex
      interaction including insulin signaling, cytokine profile and insulin
      responsiveness, which is modulated by adiponectin and IL-1beta. In addition,
      obese pregnant women are at risk for hypertension and preeclampsia with reduced
      placental vascularity and blood flow, which would restrict placental nutrient
      delivery to the developing fetus. These sometimes opposing signals regulating
      placental function may contribute to the diversity of short and long-term
      outcomes observed in pregnant obese women. This review focuses on the changes in
      adipokines and obesity-related metabolic hormones, how these factors influence
      placental function and fetal development to contribute to long-term metabolic and
      behavioral consequences of children born to obese mothers.

PMID- 27864340
TI  - Microfluidic Tissue Mesodissection in Molecular Cancer Diagnostics.
AB  - We present a mesodissection platform that retains the advantages of laser-based
      dissection instrumentation with the speed and ease of manual dissection. Tissue
      dissection in clinical laboratories is often performed by manually scraping a
      physician-selected region from standard glass slide mounts. In this manner, costs
      associated with dissection remain low, but spatial resolution is compromised. In
      contrast, laser microdissection methods maintain spatial resolution that matches
      the requirements for analysis of important tissue heterogeneity but remains
      costly and labor intensive. We demonstrate a microfluidic tool for rapid
      extraction of histological regions of interest from formalin-fixed paraffin
      embedded tissue, which uses a simple and automated method that is compatible with
      most downstream enzymatic reactions, including protocols used for next-generation
      DNA sequencing.

PMID- 27864341
TI  - Density and Proximity of Licensed Tobacco Retailers and Adolescent Smoking.
AB  - Adolescent smoking prevention is an important issue in health care. This
      literature review describes the theoretical concept of ecological model for
      adolescent smoking and tobacco retailers and summarizes previous studies on the
      association between the density and proximity of tobacco retailers and adolescent
      smoking. We reviewed nine studies on tobacco retailer density and proximity in
      relation to adolescent smoking, published in peer-reviewed journals between 2004
      and 2014. The tobacco retailer density and proximity were correlated with
      adolescent lifetime smoking, past 12-month smoking, past 30-day smoking, and
      susceptibility to smoking. School nurses or other school health professionals may
      need to include the density and proximity of tobacco retailer factors around
      schools in school-based tobacco-use prevention programs. Health policy makers may
      need to consider zoning or licensing restrictions of tobacco retailers around
      schools for adolescent smoking prevention.

PMID- 27864343
TI  - Lessons learned from Restoring Study 329: Transparent reporting, open databases
      and network meta-analyses as the way forward.

PMID- 27864342
TI  - Systemic Levels of Estrogens and PGE2 Synthesis in Relation to Postmenopausal
      Breast Cancer Risk.
AB  - Background: Prostaglandin E2 (PGE2) induces aromatase expression in adipose
      tissue, leading to increased estrogen production that may promote the development
      and progression of breast cancer. However, few studies have simultaneously
      investigated systemic levels of PGE2 and estrogen in relation to postmenopausal
      breast cancer risk.Methods: Here, we determined urinary estrogen metabolites (EM)
      using mass spectrometry in a case-cohort study (295 incident breast cancer cases
      and 294 subcohort members), and using linear regression estimated the effect of
      urinary levels of a major PGE2 metabolite (PGE-M) on EMs. HRs for the risk of
      developing breast cancer in relation to PGE-M and EMs were compared between Cox
      regression models with and without mutual adjustment.Results: PGE-M was a
      significant predictor of estrone (E1), but not estradiol (E2) levels in
      multivariable analysis. Elevated E2 levels were associated with an increased risk
      of developing breast cancer [HRQ5vs.Q1, 1.54; 95% confidence interval (CI), 1.01
      2.35], and this association remained unchanged after adjustment for PGE-M
      (HRQ5vs.Q1, 1.52; 95% CI, 0.99-2.33). Similarly, elevated levels of PGE-M were
      associated with increased risk of developing breast cancer (HRQ4vs.Q1, 2.01; 95%
      CI, 1.01-4.29), and this association was only nominally changed after
      consideration of E1 or E2 levels.Conclusions: Urinary levels of PGE-M and
      estrogens were independently associated with future risk of developing breast
      cancer among these postmenopausal women.Impact: Increased breast cancer risk
      associated with PGE-M might not be fully explained by the estrogens-breast cancer
      association alone but also by additional effects related to inflammation. Cancer
      Epidemiol Biomarkers Prev; 26(3); 383-8. (c)2016 AACR.

PMID- 27864344
TI  - Targeting Tumor-Associated Fibroblasts for Therapeutic Delivery in Desmoplastic
      Tumors.
AB  - The off-target distribution of anticancer nanoparticles to fibroblasts creates a
      barrier to the effective treatment of desmoplastic tumors. However, we
      hypothesized that this nanoparticle detriment might be exploited to target the
      expression of secreted cytotoxic proteins from tumor-associated fibroblasts (TAF)
      as an anticancer strategy. In addressing this hypothesis, plasmids encoding the
      secretable TNF-related factor sTRAIL were loaded into lipid-coated protamine DNA
      complexes and administered by infusion in a murine xenograft model of human
      desmoplastic bladder carcinoma. Three doses were sufficient to generate
      approximately 70% of TAFs as sTRAIL-producing cells. sTRAIL triggered apoptosis
      in tumor cell nests adjacent to TAFs. Furthermore, it reverted residual
      fibroblasts to a quiescent state due to insufficient activation, further
      compromising tumor growth and remodeling the microenvironment to favor second
      wave nanotherapy. We confirmed the efficacy of this strategy in an orthotopic
      xenograft model of human pancreatic cancer, where the desmoplastic stroma is well
      known to be a major barrier to the delivery of therapeutic nanoparticles.
      Collectively, our results offer a proof of concept for the use of nanoparticles
      to modify TAFs as an effective strategy to treat desmoplastic cancers. Cancer
      Res; 77(3); 719-31. (c)2016 AACR.

PMID- 27864345
TI  - PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear
      Receptor NR4A1.
AB  - Alveolar rhabdomyosarcoma (ARMS) is a devastating pediatric disease driven by
      expression of the oncogenic fusion gene PAX3-FOXO1A. In this study, we report
      overexpression of the nuclear receptor NR4A1 in rhabdomyosarcomas that is
      sufficient to drive high expression of PAX3-FOXO1A there. RNAi-mediated silencing
      of NR4A1 decreased expression of PAX3-FOXO1A and its downstream effector genes.
      Similarly, cell treatment with the NR4A1 small-molecule antagonists 1,1-bis(3
      indolyl)-1-(p-hydroxy or p-carbomethoxyphenyl)methane (C-DIM) decreased PAX3
      FOXO1A. Mechanistic investigations revealed a requirement for the NR4A1/Sp4
      complex to bind GC-rich promoter regions to elevate transcription of the PAX3
      FOXO1A gene. In parallel, NR4A1 also regulated expression of beta1-integrin,
      which with PAX3-FOXO1A, contributed to tumor cell migration that was blocked by C
      DIM/NR4A1 antagonists. Taken together, our results provide a preclinical
      rationale for the use of NR4A1 small-molecule antagonists to treat ARMS and other
      rhabdomyosarcomas driven by PAX3-FOXO1A. Cancer Res; 77(3); 732-41. (c)2016 AACR.

PMID- 27864346
TI  - CBX4 Suppresses Metastasis via Recruitment of HDAC3 to the Runx2 Promoter in
      Colorectal Carcinoma.
AB  - Polycomb chromobox (CBX) proteins participate in the polycomb repressive complex
      (PRC1) that mediates epigenetic gene silencing and endows PRC1 with distinct
      oncogenic or tumor suppressor functions in a cell-type-dependent manner. In this
      study, we report that inhibition of cell migration, invasion, and metastasis in
      colorectal carcinoma requires CBX4-mediated repression of Runx2, a key
      transcription factor that promotes colorectal carcinoma metastasis. CBX4
      inversely correlated with Runx2 expression in colorectal carcinoma tissues, and
      the combination of high CBX4 expression and low Runx2 expression significantly
      correlated with overall survival, more so than either CBX4 or Runx2 expression
      alone. Mechanistically, CBX4 maintained recruited histone deacetylase 3 (HDAC3)
      to the Runx2 promoter, which maintained a deacetylated histone H3K27 state to
      suppress Runx2 expression. This function of CBX4 was dependent on its interaction
      with HDAC3, but not on its SUMO E3 ligase, its chromodomain, or the PRC1 complex.
      Disrupting the CBX4-HDAC3 interaction abolished Runx2 inhibition as well as the
      inhibition of cell migration and invasion. Collectively, our data show that CBX4
      may act as a tumor suppressor in colorectal carcinoma, and strategies that
      stabilize the interaction of CBX4 with HDAC3 may benefit the colorectal carcinoma
      patients with metastases. Cancer Res; 76(24); 7277-89. (c)2016 AACR.

PMID- 27864348
TI  - Systems Approaches to Cancer Biology.
AB  - Cancer systems biology aims to understand cancer as an integrated system of
      genes, proteins, networks, and interactions rather than an entity of isolated
      molecular and cellular components. The inaugural Systems Approaches to Cancer
      Biology Conference, cosponsored by the Association of Early Career Cancer Systems
      Biologists and the National Cancer Institute of the NIH, focused on the
      interdisciplinary field of cancer systems biology and the challenging cancer
      questions that are best addressed through the combination of experimental and
      computational analyses. Attendees found that elucidating the many molecular
      features of cancer inevitably reveals new forms of complexity and concluded that
      ensuring the reproducibility and impact of cancer systems biology studies will
      require widespread method and data sharing and, ultimately, the translation of
      important findings to the clinic. Cancer Res; 76(23); 6774-7. (c)2016 AACR.

PMID- 27864347
TI  - Human Pancreatic Cancer Cells Induce a MyD88-Dependent Stromal Response to
      Promote a Tumor-Tolerant Immune Microenvironment.
AB  - Cancer cells exert mastery over the local tumor-associated stroma (TAS) to
      configure protective immunity within the tumor microenvironment. The
      immunomodulatory character of pancreatic lysates of patients with cancer differs
      from those with pancreatitis. In this study, we evaluated the cross-talk between
      pancreatic cancer and its TAS in primary human cell culture models. Upon exposure
      of TAS to pancreatic cancer cell-conditioned media, we documented robust
      secretion of IL6 and IL8. This TAS response was MyD88-dependent and sufficient to
      directly suppress both CD4+ and CD8+ T-cell proliferation, inducing Th17
      polarization at the expense of Th1. We found that patients possessed a similar
      shift in circulating effector memory Th17:Th1 ratios compared with healthy
      controls. The TAS response also directly suppressed CD8+ T-cell-mediated
      cytotoxicity. Overall, our results demonstrate how TAS contributes to the
      production of an immunosuppressive tumor microenvironment in pancreatic cancer.
      Cancer Res; 77(3); 672-83. (c)2016 AACR.

PMID- 27864349
TI  - Substantial Equivalence Standards in Tobacco Governance: Statutory Clarity and
      Regulatory Precedent for the FSPTCA.
AB  - The Family Smoking Prevention and Tobacco Control Act (FSPTCA) of 2009 creates
      the first national system of premarket regulation of tobacco products in American
      history. The FDA must now review and give marketing authorization to all new
      tobacco products, based on a public health standard, before they can be legally
      marketed. Yet the law also contains an alternative pathway for market entry-the
      substantial equivalence (SE) clause-by which novel and altered tobacco products
      can be marketed by demonstrating their substantial equivalence to existing
      products. Over 99 percent of tobacco product applications sent to the FDA under
      the new law have used this mechanism, and loose application of the SE mechanism
      carries the risk of undoing the FDA's gatekeeping power under the law. We review
      the statutory and regulatory precedent for SE, examining the FSPTCA itself as
      well as regulatory precedent from drug and device regulation (from which the term
      substantial equivalence and much of the associated statutory language was
      derived). Our review of standards and scientific precedent demonstrates that
      exacting scrutiny under the public health standard should govern all SE reviews
      and that clinical data incorporating social scientific evidence should be
      routinely required for SE claims by tobacco product sponsors.

PMID- 27864350
TI  - Grit and burnout in UK doctors: a cross-sectional study across specialties and
      stages of training.
AB  - PURPOSE OF THE STUDY: Grit is characterised by the ability to persevere during
      difficulties and maintain a sustained effort over an extended period of time.
      Throughout their careers, doctors will experience many periods of stress and
      difficulty. This may result in burnout, defined by the presence of exhaustion and
      disengagement from work. This study aims to characterise the relationship between
      grit and burnout in doctors and to establish whether there are differences
      between specialties and levels of training. STUDY DESIGN: A multicentre cross
      sectional survey by questionnaire was used. Participants were recruited from
      training days and an online medical forum. The survey consisted of the Short Grit
      Scale and the Oldenburg Burnout Inventory, which examine levels of grit and
      burnout, respectively. RESULTS: 548 responses were collected. We found a weak
      negative correlation between grit and burnout in UK doctors (r=-0.243, p<0.001).
      Hospital consultants had significantly higher grit scores than trainees. The
      highest level of burnout was found among general practitioners (GPs). When GPs
      were analysed separately, the correlation between grit and resilience was not
      seen. CONCLUSIONS: An understanding of an individual's level of grit may be used
      to identify doctors at a greater risk of burnout. As a high level of grit is
      associated with less burnout, interventions to improve grit through resilience
      training should be examined. Further research is needed to understand how grit
      levels change during a doctor's career and why GPs experience higher levels of
      burnout.

PMID- 27864351
TI  - Detecting differential growth of microbial populations with Gaussian process
      regression.
AB  - Microbial growth curves are used to study differential effects of media,
      genetics, and stress on microbial population growth. Consequently, many modeling
      frameworks exist to capture microbial population growth measurements. However,
      current models are designed to quantify growth under conditions for which growth
      has a specific functional form. Extensions to these models are required to
      quantify the effects of perturbations, which often exhibit nonstandard growth
      curves. Rather than assume specific functional forms for experimental
      perturbations, we developed a general and robust model of microbial population
      growth curves using Gaussian process (GP) regression. GP regression modeling of
      high-resolution time-series growth data enables accurate quantification of
      population growth and allows explicit control of effects from other covariates
      such as genetic background. This framework substantially outperforms commonly
      used microbial population growth models, particularly when modeling growth data
      from environmentally stressed populations. We apply the GP growth model and
      develop statistical tests to quantify the differential effects of environmental
      perturbations on microbial growth across a large compendium of genotypes in
      archaea and yeast. This method accurately identifies known transcriptional
      regulators and implicates novel regulators of growth under standard and stress
      conditions in the model archaeal organism Halobacterium salinarum For yeast, our
      method correctly identifies known phenotypes for a diversity of genetic
      backgrounds under cyclohexamide stress and also detects previously unidentified
      oxidative stress sensitivity across a subset of strains. Together, these results
      demonstrate that the GP models are interpretable, recapitulating biological
      knowledge of growth response while providing new insights into the relevant
      parameters affecting microbial population growth.

PMID- 27864352
TI  - Single-cell transcriptomes identify human islet cell signatures and reveal cell
      type-specific expression changes in type 2 diabetes.
AB  - Blood glucose levels are tightly controlled by the coordinated action of at least
      four cell types constituting pancreatic islets. Changes in the proportion and/or
      function of these cells are associated with genetic and molecular pathophysiology
      of monogenic, type 1, and type 2 (T2D) diabetes. Cellular heterogeneity impedes
      precise understanding of the molecular components of each islet cell type that
      govern islet (dys)function, particularly the less abundant delta and
      gamma/pancreatic polypeptide (PP) cells. Here, we report single-cell
      transcriptomes for 638 cells from nondiabetic (ND) and T2D human islet samples.
      Analyses of ND single-cell transcriptomes identified distinct alpha, beta, delta,
      and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet
      dysfunction and diabetes were expressed in the delta and PP/gamma cell types.
      Moreover, this study revealed that delta cells specifically express receptors
      that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine
      signaling pathways implicating them as integrators of central and peripheral
      metabolic signals into the pancreatic islet. Finally, single-cell transcriptome
      profiling revealed genes differentially regulated between T2D and ND alpha, beta,
      and delta cells that were undetectable in paired whole islet analyses. This study
      thus identifies fundamental cell-type-specific features of pancreatic islet
      (dys)function and provides a critical resource for comprehensive understanding of
      islet biology and diabetes pathogenesis.

PMID- 27864357
TI  - Global region of birth is an independent risk factor for type 2 diabetes in
      Stockholm, Sweden.
AB  - Background: In Stockholm, type 2 diabetes (T2D) is a public health concern and
      much more prevalent in areas with a high proportion of foreign-born individuals.
      One in five individuals in Stockholm County are born outside of Sweden, and we
      therefore investigated if global region of birth was associated with diabetes
      risk, adjusting for established risk factors. Cross-sectional data from the
      population-based Stockholm Public Health Survey 2010 ( N = 69 115) was combined
      with registry-based information on country of birth grouped into eight global
      geographical regions. Cases of T2D were identified through self-reported
      physician-diagnosed diabetes and age at diagnosis. Region of birth was the
      independent risk factor and multivariable logistic regression analysis was
      performed adjusting for the risk factors age, sex, weight status, educational
      level, multiple dietary factors, tobacco, alcohol and physical activity. T2D
      prevalence was 5.1% in the sample. Relative to Swedish-born participants, higher
      odds ratio (OR) were found in those born in Asia [OR 3.2, 95% confidence interval
      (CI) 2.2-4.7], Sub-Saharan Africa (OR 2.5, 95% CI 1.5-4.1) and North Africa/the
      Middle East (OR 2.1, 95% CI 1.6-2.8), after adjustment for established risk
      factors. Participants from Eastern Europe and Latin America had an elevated risk
      but this did not remain after adjustment for other risk factors. Region of birth
      was found to be an independent risk factor for T2D for participants born in Asia,
      Africa and the Middle East. This increased risk should be taken into
      consideration when allocating resources for prevention, detection and care.

PMID- 27864353
TI  - Identification of clinically predictive metagenes that encode components of a
      network coupling cell shape to transcription by image-omics.
AB  - The associations between clinical phenotypes (tumor grade, survival) and cell
      phenotypes, such as shape, signaling activity, and gene expression, are the basis
      for cancer pathology, but the mechanisms explaining these relationships are not
      always clear. The generation of large data sets containing information regarding
      cell phenotypes and clinical data provides an opportunity to describe these
      mechanisms. Here, we develop an image-omics approach to integrate quantitative
      cell imaging data, gene expression, and protein-protein interaction data to
      systematically describe a "shape-gene network" that couples specific aspects of
      breast cancer cell shape to signaling and transcriptional events. The actions of
      this network converge on NF-kappaB, and support the idea that NF-kappaB is
      responsive to mechanical stimuli. By integrating RNAi screening data, we identify
      components of the shape-gene network that regulate NF-kappaB in response to cell
      shape changes. This network was also used to generate metagene models that
      predict NF-kappaB activity and aspects of morphology such as cell area,
      elongation, and protrusiveness. Critically, these metagenes also have predictive
      value regarding tumor grade and patient outcomes. Taken together, these data
      strongly suggest that changes in cell shape, driven by gene expression and/or
      mechanical forces, can promote breast cancer progression by modulating NF-kappaB
      activation. Our findings highlight the importance of integrating phenotypic data
      at the molecular level (signaling and gene expression) with those at the cellular
      and tissue levels to better understand breast cancer oncogenesis.

PMID- 27864358
TI  - Effects of the histone deacetylase inhibitor 'Scriptaid' on the developmental
      competence of mouse embryos generated through round spermatid injection.
AB  - STUDY QUESTION: Can the histone deacetylase inhibitor Scriptaid improve the
      efficiency of the development of round spermatid injection (ROSI)-fertilized
      embryos in a mouse model? SUMMARY ANSWER: Treatment of ROSI mouse zygotes with
      Scriptaid increased the expression levels of several development-related genes at
      the blastocyst stage, resulting in more efficient in vitro development of the
      blastocyst and an increased birth rate of ROSI-derived embryos. WHAT IS KNOWN
      ALREADY: The full-term development of embryos derived through ROSI is
      significantly lower than that following ICSI in humans and other species. STUDY
      DESIGN, SIZE, DURATION: Oocytes, spermatozoa and round spermatids were collected
      from BDF1 (C57BL/6 * DBA/2) mice. For in vitro development experiments, mouse
      ROSI-derived zygotes were treated with Scriptaid at different concentrations (0,
      125, 250, 500 and 1000 nM) and for different exposure times (0, 6, 10, 16 or 24
      h). Next, blastocysts of the optimal Scriptaid-treated group and the non-treated
      ROSI group were separately transferred into surrogate ICR mice to compare in vivo
      development with the ICSI group (control). Each experiment was repeated at least
      three times. PARTICIPANTS/MATERIALS, SETTING, METHODS: Metaphase II (MII)
      oocytes, spermatozoa and round spermatids were obtained from sexually mature BDF1
      female or male mice. The developmental potential of embryos among the three
      groups (the ICSI, ROSI and optimal Scriptaid-treated ROSI groups) was assessed
      based on the rates of obtaining zygotes, two-cell stage embryos, four-cell stage
      embryos, blastocysts and full-term offspring. In addition, the expression levels
      of development-related genes (Oct4, Nanog, Klf4 and Sox2) were analysed using
      real-time PCR, and the methylation states of imprinted genes (H19 and Snrpn) in
      these three groups were detected using methylation-specific PCR (MS-PCR)
      sequencing following bisulfite treatment. MAIN RESULTS AND THE ROLE OF CHANCE:
      The in vitro experiments revealed that treating ROSI-derived zygotes with 250 nM
      Scriptaid for 10 h significantly improved the blastocyst formation rate (59%)
      compared with the non-treated group (38%) and further increased the birth rates
      of ROSI-derived embryos from 21% to 40% in vivo. Moreover, in ROSI-derived
      embryos, the expression of the Oct4, Nanog and Sox2 genes at the blastocyst stage
      was decreased, but the optimal Scriptaid treatment restored expression to a level
      similar to their ICSI counterparts. In addition, Scriptaid treatment moderately
      repaired the abnormal DNA methylation pattern in the imprinting control regions
      (ICRs) of H19 and Snrpn. LARGE SCALE DATA: N/A LIMITATIONS, REASONS FOR CAUTION:
      Because of the ethics regarding the use of human gametes for ROSI studies, the
      mouse model was used as an approach to explore the effects of Scriptaid on the
      developmental potential of ROSI-derived embryos. However, to determine whether
      these findings can be applied to humans, further investigation will be required.
      WIDER IMPLICATIONS OF THE FINDINGS: Scriptaid treatment provides a new means of
      improving the efficiency and safety of clinical human ROSI. STUDY
      FUNDING/COMPETING INTERESTS: The study was financially supported through grants
      from the National Key Research Program of China (No. 2016YFC1304800); the
      National Natural Science Foundation of China (Nos: 81170756, 81571486); the
      Natural Science Foundation of Shanghai (Nos: 15140901700, 15ZR1424900) and the
      Programme for Professor of Special Appointment (Eastern Scholar) at Shanghai
      Institutions of Higher Learning. There are no conflicts of interest to declare.

PMID- 27864360
TI  - Evidence-based medicine in ART.

PMID- 27864359
TI  - Endothelin-1 down-regulates matrix metalloproteinase 14 and 15 expression in
      human first trimester trophoblasts via endothelin receptor type B.
AB  - STUDY QUESTION: Does endothelin-1 (ET-1) regulate matrix metalloproteinase (MMP)
      14 and 15 production and invasion of human first trimester trophoblasts? SUMMARY
      ANSWER: ET-1 in pathophysiological concentrations down-regulates MMP14 and MMP15
      expression via endothelin receptor (ETR) type B and decreases trophoblast
      migration and invasion. WHAT IS KNOWN ALREADY: MMP14 and MMP15 are involved in
      trophoblast invasion. Impairment of invasion has been linked to pregnancy
      complications such as pre-eclampsia (PE). ET-1 is up-regulated in PE. STUDY
      DESIGN, SIZE, DURATION: In vitro study using primary human trophoblasts from 50
      first trimester placentas (gestational week 7-12). PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Trophoblasts were cultured in the absence or presence of 10-100
      nM ET-1. MMP14 and MMP15 mRNA and protein were quantified by RT-qPCR and Western
      blotting, respectively. Selective antagonists for ETRA (BQ-123) or ETRB (BQ-788)
      were used to identify ETR subtypes involved. Functional ET-1 effects were tested
      in first trimester chorionic villous explants and transwell invasion assays. The
      roles of tumor necrosis factor (TNF)-alpha (25 ng/ml) and oxygen (1%) in ET-1
      regulation of MMP14 and 15 expression were assessed by Western blotting. MAIN
      RESULTS AND THE ROLE OF CHANCE: ET-1 down-regulated MMP14 and MMP15 mRNA (-21%
      and -26%, respectively, P < 0.05) and protein levels (-18% and -22%,
      respectively, P < 0.05). This effect was mediated via ETRB. ET-1 decreased
      trophoblast outgrowth in placental explants (-24%, P < 0.05) and trophoblast
      invasion (-26%, P <= 0.01). TNF-alpha enhanced ET-1 mediated MMP15 down
      regulation (by 10%, P < 0.05), whereas hypoxia abolished the effect of ET-1 on
      both MMPs. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Only primary
      trophoblasts were used in this study. Since trophoblast yield from first
      trimester placental material is limited, further aspects of MMP14 and 15
      regulation could not be characterized. Other anti-invasive factors may be altered
      by ET-1 in trophoblasts and, thus, contribute to the reduced invasion, but have
      not been investigated. Oxygen levels similar to those found in the decidua (5-8%
      O2) were not analyzed in this study. WIDER IMPLICATIONS OF THE FINDINGS: ET-1
      modifies placental function already during the first trimester of pregnancy, the
      time-window when the placental changes implicated in PE occur. Thus, our results
      improve the understanding of the placental mechanisms underlying trophoblast
      invasion and PE. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the
      Oesterreichische Nationalbank (Anniversary Fund, project number: 14796) and the
      Herzfelder'sche Familienstiftung (to J.P.; number: 00685). AMM received funding
      from the Austrian Science Fund FWF (W1241) and the Medical University Graz
      through the PhD Program Molecular Fundamentals of Inflammation (DK-MOLIN). The
      authors have no conflict of interest.

PMID- 27864361
TI  - Causes of male infertility: a 9-year prospective monocentre study on 1737
      patients with reduced total sperm counts.
AB  - STUDY QUESTION: What are the primary causes of severe male factor infertility?
      SUMMARY ANSWER: Although 40% of all patients showed primary causes of
      infertility, which could be subdivided into three groups based on the severity of
      their effect, ~75% of oligozoospermia cases remained idiopathic. WHAT IS KNOWN
      ALREADY: There are few large-scale epidemiological studies analyzing the causes
      of male factor infertility. STUDY DESIGN, SIZE, DURATION: A prospective clinical
      epidemiological study was conducted at the Andrology Centre, Tartu University
      Hospital between 2005 and 2013, recruiting male partners of couples failing to
      conceive a child for over >=12 months. Among 8518 patients, 1737 (20.4%) were
      diagnosed with severe male factor infertility. A reference group of fertile
      controls was comprised of 325 partners of pregnant women. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: The mean age of infertility patients and fertile controls was
      33.2 +/- 7.3 and 31.7 +/- 6.3 years, respectively. All participants were examined
      using a standardized andrology workup, accompanied by a structured medical
      interview. Hormonal analysis included serum FSH, LH and testosterone. Semen
      quality was determined in accordance to the World Health Organization
      recommendations. Cases with spermatozoa concentrations of <=5 million/ml were
      screened for chromosomal aberrations and Y-chromosomal microdeletions. MAIN
      RESULTS AND THE ROLE OF CHANCE: The primary cause of infertility was defined for
      695 of 1737 patients (~40%). The analyzed causal factors could be divided into
      absolute (secondary hypogonadism, genetic causes, seminal tract obstruction),
      severe (oncological diseases, severe sexual dysfunction) and plausible causal
      factors (congenital anomalies in uro-genital tract, acquired or secondary
      testicular damage). The latter were also detected for 11 (3.4%) men with proven
      fertility (diagnoses: unilateral cryptorchidism, testis cancer, orchitis, mumps
      orchitis). The causal factors behind the most severe forms of impaired
      spermatogenesis were relatively well understood; causes were assigned: for
      aspermia in 46/46 cases (100%), for azoospermia in 321/388 cases (82.7%), and for
      cryptozoospermia in 54/130 cases (41.5%). In contrast, 75% of oligozoospermia
      cases remained unexplained. The main cause of aspermia was severe sexual
      dysfunction (71.7% of aspermia patients). Azoospermia patients accounted for
      86.4% of all cases diagnosed with secondary hypogonadism and 97.1% of patients
      with seminal tract obstruction. Of patients with a known genetic factor, 87.4%
      had extreme infertility (azoo-, crypto- or aspermia). The prevalence of
      congenital anomalies in the uro-genital tract was not clearly correlated with the
      severity of impaired sperm production. Previously defined 'potential contributing
      factors' varicocele and leukocytospermia were excluded as the primary causes of
      male infertility. However, their incidence was >2-fold higher (31.0 vs 13.5% and
      16.1 vs 7.4%; P < 0.001) in the idiopathic infertility group compared to
      controls. In addition, the proportions of overweight (or obese) patients and
      patients suffering from a chronic disease were significantly increased in almost
      all of the patient subgroups. LIMITATIONS REASONS FOR CAUTION: The study included
      only subjects with reduced total spermatozoa counts. Thus, these findings cannot
      be automatically applied to all male factor infertility cases. WIDER IMPLICATIONS
      OF THE FINDINGS: The novel insights and improved clarity achieved in the
      comprehensive analysis regarding the absolute, causative and plausible factors
      behind male infertility, as well as the 'potential contributing factors', will be
      valuable tools in updating the current clinical guidelines. The study highlights
      knowledge gaps and reiterates an urgent need to uncover the causes and mechanisms
      behind, and potential treatments of, oligozoospermic cases, representing the
      majority of idiopathic infertility patients (86.3%). STUDY FUNDING/COMPETING
      INTERESTS: The project was financed by the EU through the ERDF, project HAPPY
      PREGNANCY, no. 3.2.0701.12-004 (M.P., M.L.) and the Estonian Research Council:
      grants PUT181 (M.P.) and IUT34-12 (M.L.). The funders had no role in study
      design, data collection and analysis, decision to publish or preparation of the
      manuscript. We have no competing interests to declare. TRAIL  REGISTRATION
      NUMBER: Not applicable.

PMID- 27864362
TI  - Identification of Lysophosphatidic Acid Receptor 1 in Astroglial Cells as a
      Target for Glial Cell Line-derived Neurotrophic Factor Expression Induced by
      Antidepressants.
AB  - Preclinical and clinical evidence suggests that glial cell line-derived
      neurotrophic factor (GDNF) is important in the therapeutic effect of
      antidepressants. A previous study demonstrated that the tricyclic antidepressant
      amitriptyline induces Galphai/o activation, which leads to GDNF expression in
      astrocytes. However, the specific target expressed in astrocytes that mediates
      antidepressant-evoked Galphai/o activation has yet to be identified. Thus, the
      current study explored the possibility that antidepressant-induced Galphai/o
      activation depends on lysophosphatidic acid receptor 1 (LPAR1), a Galphai/o
      coupled receptor. GDNF mRNA expression was examined using real-time PCR and
      Galphai/o activation was examined using the cell-based receptor assay system
      CellKeyTM in rat C6 astroglial cells and rat primary cultured astrocytes. LPAR1
      antagonists blocked GDNF mRNA expression and Galphai/o activation evoked by
      various classes of antidepressants (amitriptyline, nortriptyline, mianserin, and
      fluoxetine). In addition, deletion of LPAR1 by RNAi suppressed amitriptyline
      evoked GDNF mRNA expression. Treatment of astroglial cells with the endogenous
      LPAR agonist LPA increased GDNF mRNA expression through LPAR1, whereas treatment
      of primary cultured neurons with LPA failed to affect GDNF mRNA expression.
      Astrocytic GDNF expression evoked by either amitriptyline or LPA utilized, in
      part, transactivation of fibroblast growth factor receptor and a subsequent ERK
      cascade. The current results suggest that LPAR1 is a novel, specific target of
      antidepressants that leads to GDNF expression in astrocytes.

PMID- 27864363
TI  - Induction of Airway Allergic Inflammation by Hypothiocyanite via Epithelial
      Cells.
AB  - Hypothiocyanite (OSCN-) serves as a potent innate defense system against microbes
      in the lungs. OSCN- is generated by the catalysis of peroxidases using
      thiocyanate transported via several anion transporters, including pendrin/SLC26A4
      and hydrogen peroxide (H2O2) generated by Duox1 and Duox2. We previously
      demonstrated that expression of pendrin, peroxidases, and Duox1/Duox2 is up
      regulated in bronchial asthma patients and/or asthma model mice and that these
      molecules are important in accelerating airway inflammation. However, it remained
      unclear how activating these molecules would lead to airway inflammation. In this
      study, we examined whether OSCN- produced via the pendrin/peroxidase/Duox pathway
      causes inflammation via airway epithelial cells. In an in vitro OSCN- production
      system, OSCN-, but not H2O2, activated NF-kappaB, a transcription factor critical
      for inflammatory responses, in the airway epithelial cells. OSCN- was sensed by
      protein kinase A (PKA) followed by formation of the dimerization of PKA. The
      dimerized PKA, the active form, was critical in activating NF-kappaB. Detoxifying
      H2O2, mainly by catalase, enabled the dominant abilities of OSCN- to dimerize PKA
      and activate NF-kappaB, compared with untreated H2O2 Furthermore, OSCN- in high
      doses caused necrosis of the cells, inducing release of IL-33, a trigger to
      initiate type 2 inflammation. These results demonstrate that OSCN- in low doses
      activates NF-kappaB via PKA in airway epithelial cells, whereas OSCN- in high
      doses causes necrosis, suggesting an important role in airway allergic
      inflammation for the production of OSCN- via the pendrin/peroxidase/Duox pathway.

PMID- 27864364
TI  - Membrane Recruitment of the Non-receptor Protein GIV/Girdin (Galpha-interacting,
      Vesicle-associated Protein/Girdin) Is Sufficient for Activating Heterotrimeric G
      Protein Signaling.
AB  - GIV (aka Girdin) is a guanine nucleotide exchange factor that activates
      heterotrimeric G protein signaling downstream of RTKs and integrins, thereby
      serving as a platform for signaling cascade cross-talk. GIV is recruited to the
      cytoplasmic tail of receptors upon stimulation, but the mechanism of activation
      of its G protein regulatory function is not well understood. Here we used assays
      in humanized yeast models and G protein activity biosensors in mammalian cells to
      investigate the role of GIV subcellular compartmentalization in regulating its
      ability to promote G protein signaling. We found that in unstimulated cells GIV
      does not co-fractionate with its substrate G protein Galphai3 on cell membranes
      and that constitutive membrane anchoring of GIV in yeast cells or rapid membrane
      translocation in mammalian cells via chemically induced dimerization leads to
      robust G protein activation. We show that membrane recruitment of the GIV "Galpha
      binding and activating" motif alone is sufficient for G protein activation and
      that it does not require phosphomodification. Furthermore, we engineered a
      synthetic protein to show that recruitment of the GIV "Galpha binding and
      activating" motif to membranes via association with active RTKs, instead of via
      chemically induced dimerization, is also sufficient for G protein activation.
      These results reveal that recruitment of GIV to membranes in close proximity to
      its substrate G protein is a major mechanism responsible for the activation of
      its G protein regulatory function.

PMID- 27864365
TI  - NMR Investigation of Structures of G-protein Coupled Receptor Folding
      Intermediates.
AB  - Folding of G-protein coupled receptors (GPCRs) according to the two-stage model
      (Popot, J. L., and Engelman, D. M. (1990) Biochemistry 29, 4031-4037) is
      postulated to proceed in 2 steps: partitioning of the polypeptide into the
      membrane followed by diffusion until native contacts are formed. Herein we
      investigate conformational preferences of fragments of the yeast Ste2p receptor
      using NMR. Constructs comprising the first, the first two, and the first three
      transmembrane (TM) segments, as well as a construct comprising TM1-TM2 covalently
      linked to TM7 were examined. We observed that the isolated TM1 does not form a
      stable helix nor does it integrate well into the micelle. TM1 is significantly
      stabilized upon interaction with TM2, forming a helical hairpin reported
      previously (Neumoin, A., Cohen, L. S., Arshava, B., Tantry, S., Becker, J. M.,
      Zerbe, O., and Naider, F. (2009) Biophys. J. 96, 3187-3196), and in this case the
      protein integrates into the hydrophobic interior of the micelle. TM123 displays a
      strong tendency to oligomerize, but hydrogen exchange data reveal that the center
      of TM3 is solvent exposed. In all GPCRs so-far structurally characterized TM7
      forms many contacts with TM1 and TM2. In our study TM127 integrates well into the
      hydrophobic environment, but TM7 does not stably pack against the remaining
      helices. Topology mapping in microsomal membranes also indicates that TM1 does
      not integrate in a membrane-spanning fashion, but that TM12, TM123, and TM127
      adopt predominantly native-like topologies. The data from our study would be
      consistent with the retention of individual helices of incompletely synthesized
      GPCRs in the vicinity of the translocon until the complete receptor is released
      into the membrane interior.

PMID- 27864366
TI  - Siah2 Protein Mediates Early Events in Commitment to an Adipogenic Pathway.
AB  - Adipose tissue expansion occurs by increasing the size of existing adipocytes or
      by increasing the number of adipocytes via adipogenesis. Adipose tissue
      dysfunction in obesity is associated with adipocyte hypertrophy and impaired
      adipogenesis. We recently demonstrated that deletion of the ubiquitin ligase
      Siah2 is associated with enlarged adipocytes in lean or obese mice. In this
      study, we find that adipogenesis is impaired in 3T3-L1 preadipocytes stably
      transfected with Siah2 shRNA and that overexpression of Siah2 in non-precursor
      fibroblasts promotes adipogenesis. In the 3T3-L1 model, loss of Siah2 is
      associated with sustained beta-catenin expression post-induction, but depletion
      of beta-catenin only partially restores PPARgamma expression and adipocyte
      formation. Using wild-type and Siah2-/- adipose tissue and adipose stromal
      vascular cells, we observe that Siah2 influences the expression of several
      factors that control adipogenesis, including Wnt pathway genes, beta-catenin,
      Zfp432, and Bmp-4 Consistent with increased beta-catenin levels in shSiah2
      preadipocytes, Wnt10b is elevated in Siah2-/- adipose tissue and remains elevated
      in Siah2-/- primary stromal cells after addition of the induction mixture.
      However, addition of BMP-4 to Siah2-/- stromal cells reduces Wnt10b expression,
      reduces Zfp521 protein levels, and increases expression of Zfp423, a
      transcriptional regulator of peroxisome proliferator-activated receptor gamma
      expression that controls commitment to adipogenesis and is repressed by Zfp521.
      These results indicate that Siah2 acts upstream of BMP-4 to regulate factors that
      control the commitment of adipocyte progenitors to an adipogenic pathway. Our
      findings reveal an essential role for Siah2 in the early events that signal
      undifferentiated progenitor cells to become mature adipocytes.

PMID- 27864368
TI  - Role of the Cys Loop and Transmembrane Domain in the Allosteric Modulation of
      alpha4beta2 Nicotinic Acetylcholine Receptors.
AB  - Allosteric modulators of pentameric ligand-gated ion channels are thought to act
      on elements of the pathways that couple agonist binding to channel gating. Using
      alpha4beta2 nicotinic acetylcholine receptors and the alpha4beta2-selective
      positive modulators 17beta-estradiol (betaEST) and desformylflustrabromine
      (dFBr), we have identified pathways that link the binding sites for these
      modulators to the Cys loop, a region that is critical for channel gating in all
      pentameric ligand-gated ion channels. Previous studies have shown that the
      binding site for potentiating betaEST is in the C-terminal (post-M4) region of
      the alpha4 subunit. Here, using homology modeling in combination with mutagenesis
      and electrophysiology, we identified the binding site for potentiating dFBr on
      the top half of a cavity between the third (M3) and fourth transmembrane (M4)
      alpha-helices of the alpha4 subunit. We found that the binding sites for betaEST
      and dFBr communicate with the Cys loop, through interactions between the last
      residue of post-M4 and Phe170 of the conserved FPF sequence of the Cys loop, and
      that these interactions affect potentiating efficacy. In addition, interactions
      between a residue in M3 (Tyr309) and Phe167, a residue adjacent to the Cys loop
      FPF motif, also affect dFBr potentiating efficacy. Thus, the Cys loop acts as a
      key control element in the allosteric transduction pathway for potentiating
      betaEST and dFBr. Overall, we propose that positive allosteric modulators that
      bind the M3-M4 cavity or post-M4 region increase the efficacy of channel gating
      through interactions with the Cys loop.

PMID- 27864370
TI  - Acceptability of Strategies to Reduce Student Sitting: A Mixed-Methods Study With
      College Teachers.
AB  - BACKGROUND: As school days among adolescents include long periods of prolonged
      sitting, teachers are key agents to deliver interventions to reduce youth
      sedentary behavior. To develop an intervention, acceptability and feasibility of
      alternative strategies should be tested. We aimed to examine teachers' current
      use and willingness to use various strategies to decrease student sitting and
      potential barriers and facilitators of use. METHOD: Mixed-methods design with
      college teachers using an online cross-sectional survey (n = 192) and focus group
      interviews (n = 13). FINDINGS: Although a vast majority (87%) of the teachers
      found reducing prolonged sitting an important goal, only 47% were actually
      including practices to reduce sitting in their classroom. 89% of the teachers
      reported willingness to use at least one of the five alternative strategies
      presented. Focus groups revealed a discussion emphasis on environmental
      opportunity and motivation as key to implementation. Teachers also generated
      additional ideas for intervention content. DISCUSSION: Despite low levels of
      current sitting reduction, teachers were willing to try at least one strategy to
      reduce sitting. Results informed intervention development regarding parameters of
      use for each strategy. When possible, interventions should provide teachers with
      a variety of alternative strategies that are easy to use to reduce prolonged
      sitting.

PMID- 27864367
TI  - Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in
      Mouse Brain.
AB  - Phaseic acid (PA) is a phytohormone regulating important physiological functions
      in higher plants. Here, we show the presence of naturally occurring (-)-PA in
      mouse and rat brains. (-)-PA is exclusively present in the choroid plexus and the
      cerebral vascular endothelial cells. Purified (-)-PA has no toxicity and protects
      cultured cortical neurons against glutamate toxicity through reversible
      inhibition of glutamate receptors. Focal occlusion of the middle cerebral artery
      elicited a significant induction in (-)-PA expression in the cerebrospinal fluid
      but not in the peripheral blood. Importantly, (-)-PA induction only occurred in
      the penumbra area, indicting a protective role of PA in the brain. Indeed,
      elevating the (-)-PA level in the brain reduced ischemic brain injury, whereas
      reducing the (-)-PA level using a monoclonal antibody against (-)-PA increased
      ischemic injury. Collectively, these studies showed for the first time that (-)
      PA is an endogenous neuroprotective molecule capable of reversibly inhibiting
      glutamate receptors during ischemic brain injury.

PMID- 27864369
TI  - Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP
      Binding and the Mechanism of Polyspecificity.
AB  - P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to
      multidrug resistance in cancer; it plays important roles in determining the
      pharmacokinetics of many drugs. Understanding the structural basis of P-gp,
      substrate polyspecificity has been hampered by its intrinsic flexibility, which
      is facilitated by a 75-residue linker that connects the two halves of P-gp. Here
      we constructed a mutant murine P-gp with a shortened linker to facilitate
      structural determination. Despite dramatic reduction in rhodamine 123 and calcein
      AM transport, the linker-shortened mutant P-gp possesses basal ATPase activity
      and binds ATP only in its N-terminal nucleotide-binding domain. Nine
      independently determined structures of wild type, the linker mutant, and a
      methylated P-gp at up to 3.3 A resolution display significant movements of
      individual transmembrane domain helices, which correlated with the opening and
      closing motion of the two halves of P-gp. The open-and-close motion alters the
      surface topology of P-gp within the drug-binding pocket, providing a mechanistic
      explanation for the polyspecificity of P-gp in substrate interactions.

PMID- 27864371
TI  - Applicability of recycled aggregates in concrete piles for soft soil improvement.
AB  - The expressive generation of construction and demolition waste is stimulating
      several studies for reusing this material. The improvement of soft soils by
      concrete compaction piles has been widely applied for 40 years in some Brazilian
      cities. This technique is used to improve the bearing capacity of soft soils,
      allowing executing shallow foundations instead of deep foundations. The
      compaction piles use a high volume of material. This article explored the
      possibility of using recycled aggregates from construction waste to replace the
      natural aggregates in order to improve the bearing capacity of the soft soil,
      regarding its compressive strength. Construction wastes from different stages of
      a construction were used in order to make samples of concrete with recycled
      aggregates. The strength of concretes with natural aggregates was compared with
      the strength of concretes with recycled (fine and coarse) aggregates. Results
      show that all samples met the minimum compressive strength specified for
      compaction piles used to improve the bearing capacity of soft soils. The concrete
      with recycled aggregate from the structural stage had even higher resistances
      than the concrete with natural aggregates. This behaviour was attributed to the
      large amount of cementitious materials in the composition of this type of
      concrete. It was also observed that concrete with recycled fine aggregate has a
      superior resistance to concrete with recycled coarse aggregate.

PMID- 27864374
TI  - Classic Spotlight: Metabolic Flux-Which Way To Go?

PMID- 27864372
TI  - When Far Becomes Near.
AB  - On many occasions, people spontaneously or deliberately take the perspective of a
      person facing them rather than their own perspective. How is this done? Using a
      spatial perspective task in which participants were asked to identify objects at
      specific locations, we found that self-perspective judgments were faster for
      objects presented to the right, rather than the left, and for objects presented
      closer to the participants' own bodies. Strikingly, taking the opposing
      perspective of another person led to a reversal (i.e., remapping) of these
      effects, with reference to the other person's position (Experiment 1). A
      remapping of spatial relations was also observed when an empty chair replaced the
      other person (Experiment 2), but not when access to the other viewpoint was
      blocked (Experiment 3). Thus, when the spatial scene allows a physically feasible
      but opposing point of view, people respond as if their own bodies were in that
      place. Imagination can thus overcome perception.

PMID- 27864376
TI  - Probing function and structure of trehalose-6-phosphate phosphatases from
      pathogenic organisms suggests distinct molecular groupings.
AB  - The trehalose biosynthetic pathway is of great interest for the development of
      novel therapeutics because trehalose is an essential disaccharide in many
      pathogens but is neither required nor synthesized in mammalian hosts. As such,
      trehalose-6-phosphate phosphatase (TPP), a key enzyme in trehalose biosynthesis,
      is likely an attractive target for novel chemotherapeutics. Based on a survey of
      genomes from a panel of parasitic nematodes and bacterial organisms and by way of
      a structure-based amino acid sequence alignment, we derive the topological
      structure of monoenzyme TPPs and classify them into 3 groups. Comparison of the
      functional roles of amino acid residues located in the active site for TPPs
      belonging to different groups reveal nuanced variations. Because current
      literature on this enzyme family shows a tendency to infer functional roles for
      individual amino acid residues, we investigated the roles of the strictly
      conserved aspartate tetrad in TPPs of the nematode Brugia malayi by using a
      conservative mutation approach. In contrast to aspartate-213, the residue
      inferred to carry out the nucleophilic attack on the substrate, we found that
      aspartate-215 and aspartate-428 of BmTPP are involved in the chemistry steps of
      enzymatic hydrolysis of the substrate. Therefore, we suggest that homology-based
      inference of functionally important amino acids by sequence comparison for
      monoenzyme TPPs should only be carried out for each of the 3 groups.-Cross, M.,
      Lepage, R., Rajan, S., Biberacher, S., Young, N. D., Kim, B.-N., Coster, M. J.,
      Gasser, R. B., Kim, J.-S., Hofmann, A. Probing function and structure of
      trehalose-6-phosphate phosphatases from pathogenic organisms suggests distinct
      molecular groupings.

PMID- 27864377
TI  - Mitochondrial and redox abnormalities in autism lymphoblastoid cells: a sibling
      control study.
AB  - Autism spectrum disorder (ASD) is associated with physiological abnormalities,
      including abnormal redox and mitochondrial metabolism. Lymphoblastoid cell lines
      (LCLs) from some children with ASD exhibit increased oxidative stress, decreased
      glutathione redox capacity, and highly active mitochondria with increased
      vulnerability to reactive oxygen species (ROS). Because unaffected siblings
      (Sibs) of individuals with ASD share some redox abnormalities, we sought to
      determine whether LCLs from Sibs share ASD-associated mitochondrial
      abnormalities. We evaluated mitochondrial bioenergetics in 10 sets of LCLs from
      children with ASD, Sibs, and unrelated/unaffected controls (Cons) after acute
      increases in ROS. Additionally, intracellular glutathione and uncoupling protein
      2 (UCP2) gene expressions were quantified. Compared to Sib LCLs, ASD LCLs
      exhibited significantly higher ATP-linked respiration, higher maximal and reserve
      respiratory capacity, and greater glycolysis and glycolytic reserve. ASD LCLs
      exhibited a significantly greater change in these parameters, with acute
      increases in ROS compared to both Sib and Con LCLs. Compared to Con, both ASD and
      Sib LCLs exhibited significantly higher proton leak respiration. Consistent with
      this, intracellular glutathione redox capacity was decreased and UCP2 gene
      expression was increased in both ASD and Sib compared to Con LCLs. These data
      indicate that mitochondrial respiratory function, not abnormal redox homeostasis,
      distinguishes ASD from unaffected LCLs.-Rose, S., Bennuri, S. C., Wynne, R.,
      Melnyk, S., James, S. J., Frye, R. E. Mitochondrial and redox abnormalities in
      autism lymphoblastoid cells: a sibling control study.

PMID- 27864378
TI  - Loss of scleraxis in mice leads to geometric and structural changes in cortical
      bone, as well as asymmetry in fracture healing.
AB  - Scleraxis (Scx) is a known regulator of tendon development, and recent work has
      identified the role of Scx in bone modeling. However, the role of Scx in fracture
      healing has not yet been explored. This study was conducted to identify the role
      of Scx in cortical bone development and fracture healing. Scx green fluorescent
      protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to
      assess bone morphometry and the effects of fracture healing on Scx localization
      and gene expression, as well as callus healing response. Botulinum toxin (BTX)
      was used to investigate muscle unloading effects on callus shape. Scx-mutant long
      bones had structural and mechanical defects. Scx gene expression was elevated and
      bmp4 was decreased at 24 h after fracture. ScxGFP+ cells were localized
      throughout the healing callus after fracture. Scx-mutant mice demonstrated
      disrupted callus healing and asymmetry. Asymmetry of Scx-mutant callus was not
      due to muscle unloading. Wild-type littermates (age matched) served as controls.
      This is the first study to explore the role of Scx in cortical bone mechanics and
      fracture healing. Deletion of Scx during development led to altered long bone
      properties and callus healing. This study also demonstrated that Scx may play a
      role in the periosteal response during fracture healing.-McKenzie, J. A.,
      Buettmann, E., Abraham, A. C., Gardner, M. J., Silva, M. J., Killian, M. L. Loss
      of scleraxis in mice leads to geometric and structural changes in cortical bone,
      as well as asymmetry in fracture healing.

PMID- 27864379
TI  - Foxn4 promotes gene expression required for the formation of multiple motile
      cilia.
AB  - Multiciliated cell (MCC) differentiation involves extensive organelle biogenesis
      required to extend hundreds of motile cilia. Key transcriptional regulators known
      to drive the gene expression required for this organelle biogenesis are activated
      by the related coiled-coil proteins Multicilin and Gemc1. Here we identify foxn4
      as a new downstream target of Multicilin required for MCC differentiation in
      Xenopus skin. When Foxn4 activity is inhibited in Xenopus embryos, MCCs show
      transient ciliogenesis defects similar to those seen in mutants of Foxj1, a known
      key regulator of genes required for motile ciliation. RNAseq analysis indicates
      that Foxn4 co-activates some Foxj1 target genes strongly and many Foxj1 targets
      weakly. ChIPseq suggests that whereas Foxn4 and Foxj1 frequently bind to
      different targets at distal enhancers, they largely bind together at MCC gene
      promoters. Consistent with this co-regulation, cilia extension by MCCs is more
      severely compromised in foxn4 and foxj1 double mutants than in single mutants. In
      contrast to Foxj1, Foxn4 is not required to extend a single motile cilium by
      cells involved in left-right patterning. These results indicate that Foxn4
      complements Foxj1 transcriptionally during MCC differentiation, thereby shaping
      the levels of gene expression required for the timely and complete biogenesis of
      multiple motile cilia.

PMID- 27864380
TI  - Setd5 is essential for mammalian development and the co-transcriptional
      regulation of histone acetylation.
AB  - SET domain-containing proteins play a vital role in regulating gene expression
      during development through modifications in chromatin structure. Here we show
      that SET domain-containing 5 (Setd5) is divergently transcribed with
      Gt(ROSA26)Sor, is necessary for mammalian development, and interacts with the
      PAF1 co-transcriptional complex and other proteins. Setd5-deficient mouse embryos
      exhibit severe defects in neural tube formation, somitogenesis and cardiac
      development, have aberrant vasculogenesis in embryos, yolk sacs and placentas,
      and die between embryonic day 10.5 and 11.5. Setd5-deficient embryonic stem cells
      have impaired cellular proliferation, increased apoptosis, defective cell cycle
      progression, a diminished ability to differentiate into cardiomyocytes and
      greatly perturbed gene expression. SETD5 co-immunoprecipitates with multiple
      components of the PAF1 and histone deacetylase-containing NCoR complexes and is
      not solely required for major histone lysine methylation marks. In the absence of
      Setd5, histone acetylation is increased at transcription start sites and near
      downstream regions. These findings suggest that SETD5 functions in a manner
      similar to yeast Set3p and Drosophila UpSET, and that it is essential for
      regulating histone acetylation during gene transcription.

PMID- 27864383
TI  - Use of Pharmacogenetic Information in the Treatment of Cardiovascular Disease.
AB  - BACKGROUND: In 1964, Robert A. O'Reilly's research group identified members of a
      family who required remarkably high warfarin doses (up to 145 mg/day, 20 times
      the average dose) to achieve appropriate anticoagulation. Since this time,
      pharmacogenetics has become a mainstay of cardiovascular science, and genetic
      variants have been implicated in several fundamental classes of medications used
      in cardiovascular medicine. CONTENT: In this review, we discuss genetic variants
      that affect drug response to 3 classes of cardiovascular drugs: statins, platelet
      P2Y12 inhibitors, and anticoagulants. These genetic variations have
      pharmacodynamic and pharmacokinetic effects and have been shown to explain
      differences in drug response such as lipid lowering, prevention of cardiovascular
      disease, and prevention of stroke, as well as incidence of adverse events such as
      musculoskeletal side effects and bleeding. Several groups have begun to implement
      pharmacogenetics testing as part of routine clinical care with the goal of
      improving health outcomes. Such strategies identify both patients at increased
      risk of adverse outcomes and alternative strategies to mitigate this risk as well
      as patients with "normal" genotypes, who, armed with this information, may have
      increased confidence and adherence to prescribed medications. While much is known
      about the genetic variants that underlie these effects, translation of this
      knowledge into clinical practice has been hampered by difficulty in implementing
      cost-effective, point-of-care tools to improve physician decision-making as well
      as a lack of data, as of yet, demonstrating the efficacy of using genetic
      information to improve health. SUMMARY: Many genetic variants that affect
      individual responses to drugs used in cardiovascular disease prevention and
      treatment have been described. Further study of these variants is needed before
      successful implementation into clinical practice.

PMID- 27864381
TI  - Dynein light chain DLC-1 promotes localization and function of the PUF protein
      FBF-2 in germline progenitor cells.
AB  - PUF family translational repressors are conserved developmental regulators, but
      the molecular function provided by the regions flanking the PUF RNA-binding
      domain is unknown. In C. elegans, the PUF proteins FBF-1 and FBF-2 support
      germline progenitor maintenance by repressing production of meiotic proteins and
      use distinct mechanisms to repress their target mRNAs. We identify dynein light
      chain DLC-1 as an important regulator of FBF-2 function. DLC-1 directly binds to
      FBF-2 outside of the RNA-binding domain and promotes FBF-2 localization and
      function. By contrast, DLC-1 does not interact with FBF-1 and does not contribute
      to FBF-1 activity. Surprisingly, we find that the contribution of DLC-1 to FBF-2
      activity is independent of the dynein motor. Our findings suggest that PUF
      protein localization and activity are mediated by sequences flanking the RNA
      binding domain that bind specific molecular partners. Furthermore, these results
      identify a new role for DLC-1 in post-transcriptional regulation of gene
      expression.

PMID- 27864384
TI  - Reconciling Systems for Acute Myocardial Infarction Definition and Coding
      Classification.

PMID- 27864382
TI  - Molecular dynamics of Dkk4 modulates Wnt action and regulates meibomian gland
      development.
AB  - Secreted Dickkopf (Dkk) proteins are major Wnt pathway modulators during organ
      development. Dkk1 has been widely studied and acts as a general Wnt inhibitor.
      However, the molecular function of other Dkks remains largely unknown. Here, we
      show that Dkk4 selectively inhibits a subset of Wnts, but is further inactivated
      by proteolytic cleavage. Meibomian gland (MG) formation is employed as a model
      where Dkk4 and its Wnt targets are expressed. Skin-specific expression of Dkk4
      arrests MG growth at early germ phase, which is similar to that observed in Eda
      ablated Tabby mice. Consistent with transient Dkk4 action, intact Dkk4 inhibits
      MG extension but the cleaved form progressively increases during MG development
      with a concomitant upswing in Wnt activity. Furthermore, both Dkk4 and its
      receptor (and Wnt co-receptor) Lrp6 are direct Eda targets during MG induction.
      In cell and organotypic cultures, Dkk4 inhibition is eliminated by elevation of
      Lrp6. Also, Lrp6 upregulation restores MG formation in Tabby mice. Thus, the
      dynamic state of Dkk4 itself and its interaction with Lrp6 modulates Wnt function
      during MG development, with a novel limitation of Dkk4 action by proteolytic
      cleavage.

PMID- 27864385
TI  - One Shot to Rule Out: Does the Limit of Detection of a High-Sensitivity Troponin
      Assay Hit the Mark?

PMID- 27864386
TI  - A Roadmap to Successful Clinical Proteomics.

PMID- 27864388
TI  - Payer Perspectives on Coverage of Biomarker Testing in Cardiovascular Disease.

PMID- 27864389
TI  - Troponin Autoantibodies: From Assay Interferent to Mediator of Cardiotoxicity.

PMID- 27864387
TI  - Increased Trimethylamine N-Oxide Portends High Mortality Risk Independent of
      Glycemic Control in Patients with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Recent studies show a mechanistic link between intestinal microbial
      metabolism of dietary phosphatidylcholine and coronary artery disease
      pathogenesis. Concentrations of a proatherogenic gut microbe-generated
      metabolite, trimethylamine N-oxide (TMAO), predict increased incident
      cardiovascular disease risks in multiple cohorts. TMAO concentrations are
      increased in patients with type 2 diabetes mellitus (T2DM), but their prognostic
      value and relation to glycemic control are unclear. METHODS: We examined the
      relationship between fasting TMAO and 2 of its nutrient precursors, choline and
      betaine, vs 3-year major adverse cardiac events and 5-year mortality in 1216
      stable patients with T2DM who underwent elective diagnostic coronary angiography.
      RESULTS: TMAO [4.4 MUmol/L (interquartile range 2.8-7.7 MUmol/L) vs 3.6 (2.3-5.7
      MUmol/L); P < 0.001] and choline concentrations were higher in individuals with
      T2DM vs healthy controls. Within T2DM patients, higher plasma TMAO was associated
      with a significant 3.0-fold increased 3-year major adverse cardiac event risk (P
      < 0.001) and a 3.6-fold increased 5-year mortality risk (P < 0.001). Following
      adjustments for traditional risk factors and high-sensitivity C-reactive protein,
      glycohemoglobin, and estimated glomerular filtration rate, increased TMAO
      concentrations remained predictive of both major adverse cardiac events and
      mortality risks in T2DM patients [e.g., quartiles 4 vs 1, hazard ratio 2.05 (95%
      CI, 1.31-3.20), P < 0.001; and 2.07 (95% CI, 1.37-3.14), P < 0.001,
      respectively]. CONCLUSIONS: Fasting plasma concentrations of the proatherogenic
      gut microbe-generated metabolite TMAO are higher in diabetic patients and portend
      higher major adverse cardiac events and mortality risks independent of
      traditional risk factors, renal function, and relationship to glycemic control.

PMID- 27864392
TI  - BET 1: Trimethoprim-sulfamethoxazole in uncomplicated skin abscess.
AB  - A short cut review was carried out to establish whether incision and drainage
      followed by treatment with oral trimethoprim-sulfamethoxazole is better than
      incision and drainage alone at treating patients with uncomplicated skin
      abscesses. One hundred and ninety-seven papers were found using the reported
      searches, of which three presented the best evidence to answer the clinical
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of these papers are
      tabulated. It is concluded that trimethoprim-sulfamethoxazole may help with
      abscess cure, and will decrease abscess formation at new sites.

PMID- 27864391
TI  - A woman with swelling of the neck.

PMID- 27864394
TI  - BET 2: Low-dose ketamine for acute pain in the ED.
AB  - A short cut review was carried out to establish whether low-dose ketamine is
      better than morphine at safely and effectively reducing pain scores in ED
      patients with acute pain who do not respond to conventional therapies. One
      hundred and thirty-two papers were found using the reported searches, of these
      three presented the best evidence to answer the clinical question. The author,
      date and country of publication, patient group studied, study type, relevant
      outcomes, results and study weaknesses of these best papers are tabulated. It is
      concluded that the evidence is limited, but that ketamine can be an effective
      alternative or adjunct to intravenous opioid pain medications and in some
      instances may provide more effective pain relief when compared with opioids.

PMID- 27864395
TI  - The blue patient.

PMID- 27864396
TI  - Work Life and Family Life Collide: Online Support for New Fathers.
AB  - The purpose of this investigation was to analyze online discussions about
      parental leave in relation to the work lives and private lives of new fathers. A
      netnographic study of nearly 100 discussion threads from a freely accessible
      online forum for fathers was conducted. Data were coded, sorted, and categorized
      by qualitative similarities and differences. The results of the study indicate
      that new fathers seek Internet forums to discuss work-related topics. Parental
      leave can provoke worries and anxiety related to management and co-worker
      attitudes which can create concern that they should be back at work. The results
      are presented in two categories: (a) attitudes expressed by employers and
      colleagues and (b) leaving work but longing to be back. The phenomenon of
      parental leave for fathers is more complex than simply "for" or "against"
      attitudes. Fathers can use Internet forums to discuss their experiences, fears,
      and anxiety and provide reasonable accommodations for both work and family life.

PMID- 27864397
TI  - Sociodemographic distribution of non-communicable disease risk factors in rural
      Uganda: a cross-sectional study.

PMID- 27864398
TI  - Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a
      systematic review and meta-analysis.

PMID- 27864400
TI  - Malaria in Uganda: school-based rapid diagnostic testing and treatment.

PMID- 27864401
TI  - Change in body size and mortality: a systematic review and meta-analysis.
AB  - Background: : Observational studies have reported that weight loss in later life
      is associated with an increased risk of mortality. However, the association with
      weight gain is unclear. We conducted a systematic review and meta-analysis of
      prospective studies assessing the association of weight gain and loss, and
      mortality. Methods: : We searched PubMed, Scopus and Web of Science for articles
      published before 5 September 2015. We included prospective studies that reported
      enough information to extract hazard ratios (HRs) with the corresponding 95%
      confidence intervals (CIs) for the association between weight gain and/or weight
      loss, and all-cause and cause-specific mortality. The estimates were pooled using
      a random-effects model. Meta-regression models were fitted to explore sources of
      potential between-study heterogeneity. Results: : A total of 25 (providing data
      from 437 772 participants with 34 038 deaths from all causes) and 24 studies (434
      694 participants with 31 978 deaths) presented results for the exposures, weight
      loss and weight gain. Weight loss compared with a stable weight was associated
      with an increased risk of all-cause (pooled HR: 1.45; 95% CI: 1.34, 1.58), and
      cardiovascular disease (CVD) mortality (1.50; 1.32, 1.70) and a slightly
      increased risk of cancer mortality (1.19; 0.97, 1.46). Weight gain was associated
      with an increased risk of CVD mortality (1.21; 1.07, 1.36) and a slightly
      increased risk of all-cause mortality (1.07; 1.01, 1.13) and cancer mortality
      (1.04; 0.96, 1.13). Considerable heterogeneity was observed; the method used to
      ascertain body size and the proportion of the baseline sample included in the
      final analysis explained most of the heterogeneity. Conclusion: : Weight loss and
      weight gain in midlife are associated with increased risk of all-cause and CVD
      mortality.

PMID- 27864399
TI  - Novel genetic loci associated with long-term deterioration in blood lipid
      concentrations and coronary artery disease in European adults.
AB  - Background: Cross-sectional genome-wide association studies have identified
      hundreds of loci associated with blood lipids and related cardiovascular traits,
      but few genetic association studies have focused on long-term changes in blood
      lipids. Methods: Participants from the GLACIER Study (Nmax = 3492) were genotyped
      with the MetaboChip array, from which 29 387 SNPs (single nucleotide
      polymorphisms; replication, fine-mapping regions and wildcard SNPs for lipid
      traits) were extracted for association tests with 10-year change in total
      cholesterol (DeltaTC) and triglycerides (DeltaTG). Four additional prospective
      cohort studies (MDC, PIVUS, ULSAM, MRC Ely; Nmax = 8263 participants) were used
      for replication. We conducted an in silico look-up for association with coronary
      artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and
      Meta-analysis (CARDIoGRAMplusC4D) Consortium (N ~ 190 000) and functional
      annotation for the top ranking variants. Results: In total, 956 variants were
      associated (P < 0.01) with either DeltaTC or DeltaTG in GLACIER. In GLACIER,
      chr19:50121999 at APOE was associated with DeltaTG and multiple SNPs in the
      APOA1/A4/C3/A5 region at genome-wide significance (P < 5 * 10-8), whereas
      variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide
      significance (P < 1.7 * 10-6). The rs7412 variant at APOE was associated with
      DeltaTC in GLACIER (P < 1.7 * 10-6). In pooled analyses of all cohorts, 139 SNPs
      at six and five loci were associated with DeltaTC and for DeltaTG, respectively
      (P < 10-3). Of these, a variant at CAPN3 (P = 1.2 * 10-4), multiple variants at
      HPR (Pmin = 1.5 * 10-6) and a variant at SIX5 (P = 1.9 * 10-4) showed evidence
      for association with CAD. Conclusions: We identified seven novel genomic regions
      associated with long-term changes in blood lipids, of which three also raise CAD
      risk.

PMID- 27864402
TI  - Molecular genetic contributions to self-rated health.
AB  - Background: Poorer self-rated health (SRH) predicts worse health outcomes, even
      when adjusted for objective measures of disease at time of rating. Twin studies
      indicate SRH has a heritability of up to 60% and that its genetic architecture
      may overlap with that of personality and cognition. Methods: We carried out a
      genome-wide association study (GWAS) of SRH on 111 749 members of the UK Biobank
      sample. Univariate genome-wide complex trait analysis (GCTA)-GREML analyses were
      used to estimate the proportion of variance explained by all common autosomal
      single nucleotide polymorphisms (SNPs) for SRH. Linkage disequilibrium (LD) score
      regression and polygenic risk scoring, two complementary methods, were used to
      investigate pleiotropy between SRH in the UK Biobank and up to 21 health-related
      and personality and cognitive traits from published GWAS consortia. Results: The
      GWAS identified 13 independent signals associated with SRH, including several in
      regions previously associated with diseases or disease-related traits. The
      strongest signal was on chromosome 2 (rs2360675, P = 1.77 x 10 -10 ) close to
      KLF7 . A second strong peak was identified on chromosome 6 in the major
      histocompatibility region (rs76380179, P = 6.15 x 10 -10 ). The proportion of
      variance in SRH that was explained by all common genetic variants was 13%.
      Polygenic scores for the following traits and disorders were associated with SRH:
      cognitive ability, education, neuroticism, body mass index (BMI), longevity,
      attention-deficit hyperactivity disorder (ADHD), major depressive disorder,
      schizophrenia, lung function, blood pressure, coronary artery disease, large
      vessel disease stroke and type 2 diabetes. Conclusions: Individual differences in
      how people respond to a single item on SRH are partly explained by their genetic
      propensity to many common psychiatric and physical disorders and psychological
      traits.

PMID- 27864404
TI  - Causation, mediation and explanation.

PMID- 27864403
TI  - Using group data to treat individuals: understanding heterogeneous treatment
      effects in the age of precision medicine and patient-centred evidence.
AB  - Although often conflated, determining the best treatment for an individual (the
      task of a doctor) is fundamentally different from determining the average effect
      of treatment in a population (the purpose of a trial). In this paper, we review
      concepts of heterogeneity of treatment effects (HTE) essential in providing the
      evidence base for precision medicine and patient-centred care, and explore some
      inherent limitations of using group data (e.g. from a randomized trial) to guide
      treatment decisions for individuals. We distinguish between person-level HTE
      (i.e. that individuals experience different effects from a treatment) and group
      level HTE (i.e. that subgroups have different average treatment effects), and
      discuss the reference class problem, engendered by the large number of
      potentially informative subgroupings of a study population (each of which may
      lead to applying a different estimated effect to the same patient), and the scale
      dependence of group-level HTE. We also review the limitations of conventional
      'one-variable-at-a-time' subgroup analyses and discuss the potential benefits of
      using more comprehensive subgrouping schemes that incorporate information on
      multiple variables, such as those based on predicted outcome risk. Understanding
      the conceptual underpinnings of HTE is critical for understanding how studies can
      be designed, analysed, and interpreted to better inform individualized clinical
      decisions.

PMID- 27864405
TI  - Prenatal exposure to mercury and neuropsychological development in young
      children: the role of fish consumption.
AB  - Background: Vulnerability of the central nervous system to mercury exposure is
      increased during early development. The aim of this study is to evaluate the
      association between prenatal exposure to mercury and child neuropsychological
      development in high-fish-intake areas in Spain. Methods: Study subjects were 1362
      children, participants in the INMA (Environment and Childhood) birth cohort
      study. Cord blood total mercury (CB-Hg) and cord polyunsaturated fatty acids
      (PUFA) concentrations were analysed in samples collected between 2004 and 2008.
      Child neuropsychological development was assessed at age 4-5 years by the
      McCarthy Scales of Children's Abilities (MSCA). Socio-demographic, lifestyle and
      dietary information was obtained by questionnaires administered during pregnancy
      and childhood. Results: The geometric mean of CB-Hg was 8.8 ug/L [95% confidence
      interval (CI) 8.4, 9.2]. A doubling in CB-Hg was associated with higher scores in
      most of the MSCA scales ( beta =1.29; 95% CI 0.28, 2.31 for the general cognitive
      scale). The association between CB-Hg and the scores obtained on the scales was
      inverse among children whose mothers consumed fewer than three weekly servings of
      fish during the first trimester of pregnancy, although confidence intervals did
      not exclude the null ( beta =-1.20; 95% CI -2.62, 0.22 for the perceptive
      manipulative scale and beta =-3.06; 95% CI -6.37, 0.24 for the general cognitive
      scale). An inverse association between CB-Hg and the scores on the motor scale
      was also suggested for children with an n-6/n-3 PUFA ratio above the median (
      beta =-0.23; 95% CI -0.87, 0.40, interaction p -value=0.03). Conclusion: The
      relationship between CB-Hg concentrations and child neuropsychological
      development was influenced by maternal nutritional factors, such as fish
      consumption and the PUFA status.

PMID- 27864406
TI  - Explanation in causal inference: developments in mediation and interaction.

PMID- 27864408
TI  - The epidemiology of two things considered together. Commentary on: Explanation in
      Causal Inference: Developments in Mediation and Interaction, by Tyler J.
      VanderWeele.

PMID- 27864409
TI  - Mediation, interaction, interference for social epidemiology.

PMID- 27864411
TI  - Commentary: Increasing uptake of HIV testing: gifts are good but more is needed.

PMID- 27864410
TI  - Effectiveness of motivational interviewing interventions on medication adherence
      in adults with chronic diseases: a systematic review and meta-analysis.
AB  - Background: Medication adherence is frequently suboptimal in adults with chronic
      diseases, resulting in negative consequences. Motivational interviewing (MI) is a
      collaborative conversational style for strengthening a person's motivation and
      commitment to change. We aimed to assess whether MI interventions are effective
      to enhance medication adherence in adults with chronic diseases and to explore
      the effect of individual MI intervention characteristics. Methods: We searched
      electronic databases and reference lists of relevant articles to find randomized
      controlled trials (RCTs) that assessed MI intervention effectiveness on
      medication adherence in adults with chronic diseases. A random-effects model was
      used to estimate a pooled MI intervention effect size and its heterogeneity (I 2
      ). We also explored the effects of individual MI characteristics on MI
      intervention effect size using a meta-regression with linear mixed model.
      Results: : Nineteen RCTs were identified, and 16 were included in the meta
      analysis. The pooled MI intervention effect size was 0.12 [95% confidence
      interval (CI) = (0.05, 0.20), I 2 = 1%]. Interventions that were based on MI only
      [beta = 0.183, 95% CI = (0.004, 0.362)] or those in which interventionists were
      coached during intervention implementation [beta = 0.465, 95% CI = (0.028,
      0.902)] were the most effective. MI interventions that were delivered solely face
      to face were more effective than those that were delivered solely by phone [beta
      = 0.270, 95% CI = (0.041, 0.498)]. Conclusions: This synthesis of RCTs suggests
      that MI interventions might be effective at enhancing of medication adherence in
      adults treated for chronic diseases. Further research is however warranted, as
      the observed intervention effect size was small.

PMID- 27864412
TI  - Multilevel regression modelling to investigate variation in disease prevalence
      across locations.
AB  - In this article, we show how to investigate the role of individual (personal)
      risk factors in outcome prevalence in multicentre studies with multilevel
      modelling. The variation in outcome prevalence is modelled by introducing a
      random intercept. In the next step, the empty model is compared with the model
      containing the risk factor(s). Because the outcome is dichotomous, this
      comparison can only be carried out after having rescaled the models' parameter
      values to the variance of an underlying continuous variable. We illustrate this
      approach with data from Phase Two of the International Study of Asthma and
      Allergies in Childhood (ISAAC) and provide a corresponding Stata do-file.

PMID- 27864413
TI  - Cohort Profile: Collaboration of Observational HIV Epidemiological Research
      Europe (COHERE) in EuroCoord.

PMID- 27864416
TI  - Correction.

PMID- 27864414
TI  - Author's reply: The role of potential outcomes thinking in assessing mediation
      and interaction.

PMID- 27864417
TI  - Tumor Thickness and Mitotic Rate Robustly Predict Melanoma-Specific Survival in
      Patients with Primary Vulvar Melanoma: A Retrospective Review of 100 Cases.
AB  - Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar
      malignancy. Despite their distinct anatomic site and unique molecular-genetic
      alterations, PVMs are staged according to the American Joint Committee on Cancer
      (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether
      parameters derived for PCM also apply to PVM remain a critical yet largely
      unexplored clinical question. The objective of this study was to determine the
      parameters predictive of survival in PVM.Experimental Design: We retrospectively
      reviewed 100 patients with PVM and determined associations between clinical and
      histopathologic parameters and disease-specific survival (DSS) and overall
      survival (OS).Results: Univariate Cox regression analysis demonstrated older age
      (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration,
      lymphovascular invasion, perineural invasion, microscopic satellitosis, and
      absence of precursor nevus associated with decreased OS. Furthermore, age,
      midline, and/or multifocal involvement, greater tumor thickness, higher dermal
      mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural
      invasion, and microscopic satellitosis associated with decreased DSS.
      Multivariate analysis demonstrated tumor thickness, dermal mitotic rate,
      lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus
      independently predicted shorter OS. Only tumor thickness and increased dermal
      mitotic rate (>=2/mm2) independently predicted reduced DSS. In comparison with
      the AJCC T-category, a novel, bivariate T-category based only on tumor thickness
      and dermal mitotic rate robustly predicted OS and DSS in our patient
      cohort.Conclusions: In the largest single institutional study of PVM, we
      demonstrate a combination of tumor thickness and mitotic rate comprise a simple
      but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8);
      2093-104. (c)2016 AACR.

PMID- 27864418
TI  - AMPK-ULK1-Mediated Autophagy Confers Resistance to BET Inhibitor JQ1 in Acute
      Myeloid Leukemia Stem Cells.
AB  - Purpose: Bromodomain and extraterminal domain (BET) inhibitors are promising
      epigenetic agents for the treatment of various subsets of acute myeloid leukemia
      (AML). However, the resistance of leukemia stem cells (LSC) to BET inhibitors
      remains a major challenge. In this study, we evaluated the mechanisms underlying
      LSC resistance to the BET inhibitor JQ1.Experimental Design: We evaluated the
      levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines
      and primary CD34+CD38- leukemic blasts obtained from AML cases with normal
      karyotype without recurrent mutations.Results: JQ1 effectively induced apoptosis
      in a concentration-dependent manner in JQ1-sensitive AML cells. However, in JQ1
      resistant AML LSCs, JQ1 induced little apoptosis and led to upregulation of
      beclin-1, increased LC3-II lipidation, formation of autophagosomes, and
      downregulation of p62/SQSTM1. Inhibition of autophagy by pharmacologic inhibitors
      or knockdown of beclin-1 using specific siRNA enhanced JQ1-induced apoptosis in
      resistant cells, indicating that prosurvival autophagy occurred in these cells.
      Independent of mTOR signaling, activation of the AMPK (pThr172)/ULK1 (pSer555)
      pathway was found to be associated with JQ1-induced autophagy in resistant cells.
      AMPK inhibition using the pharmacologic inhibitor compound C or by knockdown of
      AMPKalpha suppressed autophagy and promoted JQ1-induced apoptosis in AML
      LSCs.Conclusions: These findings revealed that prosurvival autophagy was one of
      the mechanisms involved in the resistance AML LSCs to JQ1. Targeting the
      AMPK/ULK1 pathway or inhibition of autophagy could be an effective therapeutic
      strategy for combating resistance to BET inhibitors in AML and other types of
      cancer. Clin Cancer Res; 23(11); 2781-94. (c)2016 AACR.

PMID- 27864419
TI  - How Subclonal Modeling Is Changing the Metastatic Paradigm.
AB  - A concerted effort to sequence matched primary and metastatic tumors is vastly
      improving our ability to understand metastasis in humans. Compelling evidence has
      emerged that supports the existence of diverse and surprising metastatic
      patterns. Enhancing these efforts is a new class of algorithms that facilitate
      high-resolution subclonal modeling of metastatic spread. Here we summarize how
      subclonal models of metastasis are influencing the metastatic paradigm. Clin
      Cancer Res; 23(3); 630-5. (c)2016 AACR.

PMID- 27864420
TI  - The Landscape of Viral Expression Reveals Clinically Relevant Viruses with
      Potential Capability of Promoting Malignancy in Lower-Grade Glioma.
AB  - Purpose: RNA sequencing (RNA-seq) has recently proved to be effective for
      revealing novel virus-tumor associations. To get a thorough investigation of
      virus-glioma associations, we screened viruses in gliomas with RNA-seq data from
      the Chinese Glioma Genome Atlas project.Experimental Design: In total, 325
      samples were enrolled into this study. Reads that failed to map to the human
      genome were aligned to viral genomes and screened for potential virus-derived
      transcripts. For quantification, VPKM was calculated according to mapped reads
      weighted by genome sizes and sequencing depth.Results: We observed that viruses
      tended to concertedly express in a certain subgroup of patients. Survival
      analysis revealed that individuals who were infected with Simian virus 40 (SV40)
      or woolly monkey sarcoma virus (WMSV) had a significantly shorter overall
      survival than those uninfected. A multivariate Cox proportional hazards model,
      taking clinical and molecular factors into account, was applied to assess the
      prognostic value of SV40 and WMSV. Both SV40 and WMSV were independent prognostic
      factors for predicting patient's survival in lower-grade gliomas. Subsequent gene
      analysis demonstrated that SV40 was correlated with regulation of transcription,
      whereas WMSV was correlated with cell-cycle phase, which indicated frequent
      proliferation of tumor cells.Conclusions: RNA-seq was sufficient to identify
      virus infection in glioma samples. SV40 and WMSV were identified to be prognostic
      markers for patients with lower-grade gliomas and showed potential values for
      targeting therapy. Clin Cancer Res; 23(9); 2177-85. (c)2016 AACR.

PMID- 27864423
TI  - The Right Stand by ASM regarding Journal Impact Factors.

PMID- 27864424
TI  - Erratum for Voelz et al., Cytokine Signaling Regulates the Outcome of
      Intracellular Macrophage Parasitism by Cryptococcus neoformans.

PMID- 27864426
TI  - Intraspinal pressure and spinal cord perfusion pressure predict neurological
      outcome after traumatic spinal cord injury.

PMID- 27864425
TI  - Isoform-Specific Biased Agonism of Histamine H3 Receptor Agonists.
AB  - The human histamine H3 receptor (hH3R) is subject to extensive gene splicing that
      gives rise to a large number of functional and nonfunctional isoforms. Despite
      the general acceptance that G protein-coupled receptors can adopt different
      ligand-induced conformations that give rise to biased signaling, this has not
      been studied for the H3R; further, it is unknown whether splice variants of the
      same receptor engender the same or differential biased signaling. Herein, we
      profiled the pharmacology of histamine receptor agonists at the two most abundant
      hH3R splice variants (hH3R445 and hH3R365) across seven signaling endpoints. Both
      isoforms engender biased signaling, notably for 4-[3-(benzyloxy)propyl]-1H
      imidazole (proxyfan) [e.g., strong bias toward phosphorylation of glycogen
      synthase kinase 3beta (GSK3beta) via the full-length receptor] and its congener 3
      (1H-imidazol-4-yl)propyl-(4-iodophenyl)-methyl ether (iodoproxyfan), which are
      strongly consistent with the former's designation as a "protean" agonist. The 80
      amino acid IL3 deleted isoform hH3R365 is more permissive in its signaling than
      hH3R445: 2-(1H-imidazol-5-yl)ethyl imidothiocarbamate (imetit), proxyfan, and
      iodoproxyfan were all markedly biased away from calcium signaling, and principal
      component analysis of the full data set revealed divergent profiles for all five
      agonists. However, most interesting was the identification of differential biased
      signaling between the two isoforms. Strikingly, hH3R365 was completely unable to
      stimulate GSK3beta phosphorylation, an endpoint robustly activated by the full
      length receptor. To the best of our knowledge, this is the first quantitative
      example of differential biased signaling via isoforms of the same G protein
      coupled receptor that are simultaneously expressed in vivo and gives rise to the
      possibility of selective pharmacological targeting of individual receptor splice
      variants.

PMID- 27864427
TI  - Dyskinesia in Treatment-Naive and Stimulant-Treated Children With ADHD.
AB  - OBJECTIVE: Stimulants are safe and effective medications for the treatment of
      ADHD. There are a number of case studies that report stimulant-induced
      dyskinesia. The aim of this study was to compare dyskinesia in a treated and a
      treatment-naive group of children with ADHD, and a healthy control group. METHOD:
      Children aged 6 to 18 years were involved in the study (n = 158). Diagnosis of
      ADHD was measured with the Mini International Neuropsychiatric Interview Kid
      (MINI Kid). Dyskinesia was assessed with the Abnormal Involuntary Movement Scale
      (AIMS). RESULTS: Before methylphenidate administration, the treated ADHD group
      showed significantly higher AIMS total score than the control group (p = .001)
      and the treatment-naive ADHD group (p < .001). We found the same pattern 1.5 hr
      after methylphenidate administration. CONCLUSION: These results call attention
      that clinicians should take special care for the possible development of
      dyskinesia during the treatment of their ADHD patients with methylphenidate.

PMID- 27864429
TI  - Association Between Auditory and Visual Continuous Performance Tests in Students
      With ADHD.
AB  - OBJECTIVE: Continuous Performance Tests (CPTs) are known to measure inattention
      and impulsivity in students with ADHD. Many CPTs utilize a visual format. It is
      accepted that auditory tasks reflect attentional demand more closely in the
      classroom. Thus, the association between deficits found by auditory and visual
      CPTs needs to be studied. We hypothesized that impulsivity would be dependent on
      sensory modality and inattention would be a unitary cross-modal construct.
      METHOD: Forty-four students with ADHD performed two CPTs (visual and auditory).
      We analyzed correlations between the variables examined by the two tasks.
      RESULTS: There were strong correlations between variables measuring inattention.
      Correlations between auditory and visual measures of impulsivity were weak.
      CONCLUSION: Inattention is partially independent of modality. In contrast,
      response inhibition is modality-specific. Although ADHD is defined regardless of
      modality, hyperactive students may exhibit deficits in the auditory modality but
      not in the visual modality or vice versa.

PMID- 27864428
TI  - Adults With Persistent ADHD: Gender and Psychiatric Comorbidities-A Population
      Based Longitudinal Study.
AB  - OBJECTIVE: The aim of the study was to evaluate associations between ADHD and
      comorbid psychiatric disorders among adults from a population-based birth cohort.
      METHOD: Participants were recruited from all children born between 1976 and 1982
      remaining in Rochester, Minnesota, after age 5. Participants with childhood ADHD
      ( n = 232; M age = 27.0 years; 72% men) and non-ADHD controls ( n = 335; M age =
      28.6 years; 63% men) completed a structured interview (M.I.N.I. International
      Neuropsychiatric Interview) assessing current ADHD status and comorbid
      psychiatric disorders. RESULTS: Among 232 with childhood ADHD, 68 (49 men, 19
      women) had persistent adult ADHD. Compared with non-ADHD controls and non
      persistent ADHD participants, adults with persistent ADHD were significantly more
      likely to have any or each of 12 psychiatric comorbidities. The associations
      retained significant or marginally significant when stratified by gender.
      Externalizing psychiatric disorders were more common in men (74%) and
      internalizing disorders in women (58%). CONCLUSION: Persistent ADHD is associated
      with an increased risk of comorbid psychiatric disorders in adult men and women.

PMID- 27864430
TI  - APOL1-G1 in Nephrocytes Induces Hypertrophy and Accelerates Cell Death.
AB  - People of African ancestry carrying certain APOL1 mutant alleles are at elevated
      risk of developing renal diseases. However, the mechanisms underlying APOL1
      associated renal diseases are unknown. Because the APOL1 gene is unique to humans
      and some primates, new animal models are needed to understand the function of
      APOL1 in vivo We generated transgenic Drosophila fly lines expressing the human
      APOL1 wild type allele (G0) or the predominant APOL1 risk allele (G1) in
      different tissues. Ubiquitous expression of APOL1 G0 or G1 in Drosophila induced
      lethal phenotypes, and G1 was more toxic than was G0. Selective expression of the
      APOL1 G0 or G1 transgene in nephrocytes, fly cells homologous to mammalian
      podocytes, induced increased endocytic activity and accumulation of hemolymph
      proteins, dextran particles, and silver nitrate. As transgenic flies with either
      allele aged, nephrocyte function declined, cell size increased, and nephrocytes
      died prematurely. Compared with G0-expressing cells, however, G1-expressing cells
      showed more dramatic phenotypes, resembling those observed in cultured mammalian
      podocytes overexpressing APOL1-G1. Expressing the G0 or G1 APOL1 transgene in
      nephrocytes also impaired the acidification of organelles. We conclude that
      expression of an APOL1 transgene initially enhances nephrocyte function, causing
      hypertrophy and subsequent cell death. This new Drosophila model uncovers a novel
      mechanism by which upregulated expression of APOL1-G1 could precipitate renal
      disease in humans. Furthermore, this model may facilitate the identification of
      APOL1-interacting molecules that could serve as new drug targets to treat APOL1
      associated renal diseases.

PMID- 27864432
TI  - Underemployment and mental health: comparing fixed-effects and random-effects
      regression approaches in an Australian working population cohort.
AB  - OBJECTIVES: Underemployment occurs when workers are available for more hours of
      work than offered. It is a serious problem in many Organisation for Economic Co
      operation and Development (OECD) countries, and particularly in Australia, where
      it affects about 8% of the employed population. This paper seeks to answer the
      question: does an increase in underemployment have an influence on mental health?
      METHODS: The current paper uses data from an Australian cohort of working people
      (2001-2013) to investigate both within-person and between-person differences in
      mental health associated with being underemployed compared with being fully
      employed. The main exposure was underemployment (not underemployed, underemployed
      1-5, 6-10, 11-20 and over 21 hours), and the outcome was the five-item Mental
      Health Inventory. RESULTS: Results suggest that stepwise declines in mental
      health are associated with an increasing number of hours underemployed. Results
      were stronger in the random-effects (11-20 hours =-1.53, 95% CI -2.03 to -1.03,
      p<0.001; 21 hours and over -2.24, 95% CI -3.06 to -1.43, p<0.001) than fixed
      effects models (11-20 hours =-1.11, 95% CI -1.63 to -0.58, p<0.001; 21 hours and
      over -1.19, 95% CI -2.06 to -0.32, p=0.008). This likely reflects the fact that
      certain workers were more likely to suffer the negative effects of
      underemployment than others (eg, women, younger workers, workers in lower-skilled
      jobs and who were casually employed). CONCLUSIONS: We suggest underemployment to
      be a target of future workplace prevention strategies.

PMID- 27864431
TI  - APOL1-Mediated Cell Injury Involves Disruption of Conserved Trafficking
      Processes.
AB  - APOL1 harbors C-terminal sequence variants (G1 and G2), which account for much of
      the increased risk for kidney disease in sub-Saharan African ancestry
      populations. Expression of the risk variants has also been shown to cause injury
      to podocytes and other cell types, but the underlying mechanisms are not
      understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help
      clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2
      disease risk alleles caused near-complete lethality in D. melanogaster, with no
      effect of the G0 nonrisk APOL1 allele, corresponding to the pattern of human
      disease risk. We also observed a congruent pattern of cellular damage with tissue
      specific expression of APOL1. In particular, expression of APOL1 risk variants in
      D. melanogaster nephrocytes caused cell-autonomous accumulation of the endocytic
      tracer atrial natriuretic factor-red fluorescent protein at early stages and
      nephrocyte loss at later stages. We also observed differential toxicity of the
      APOL1 risk variants compared with the APOL1 nonrisk variants in S. cerevisiae,
      including impairment of vacuole acidification. Yeast strains defective in
      endosomal trafficking or organelle acidification but not those defective in
      autophagy displayed augmented APOL1 toxicity with all isoforms. This pattern of
      differential injury by the APOL1 risk alleles compared with the nonrisk alleles
      across evolutionarily divergent species is consistent with an impairment of
      conserved core intracellular endosomal trafficking processes. This finding should
      facilitate the identification of cell injury pathways and corresponding
      therapeutic targets of interest in these amenable experimental platforms.

PMID- 27864433
TI  - Effect of occupational physical activities on vertebral dimensions in midlife in
      the Northern Finland Birth Cohort 1966.
AB  - OBJECTIVES: The vertebral cross-sectional area (CSA) is a major determinant of
      vertebral strength. Since leisure-time physical activity (LTPA) is known to
      affect vertebral CSA, we hypothesised that engagement in physical activity at
      work might have similar effects on vertebral size. We aimed to examine the
      association between various adulthood occupational physical activities (OPA) and
      vertebral CSA, and to evaluate the association between OPA intensity and
      vertebral CSA. METHODS: We used the prospective population-based Northern Finland
      Birth Cohort 1966. Our sample consisted of 712 participants with a mean age of
      46.8 years. We assessed their engagement in various individual physical work
      activities at the ages of 31 and 46, and created overall OPA categories (high,
      moderate and low intensity), which we used in the analyses to study their
      association with vertebral CSA in middle age. Linear regression was used as the
      statistical method with adjustments for LTPA, vertebral height, body mass index
      and smoking. RESULTS: A statistically significant association was found between
      occupational sitting and smaller vertebral CSA in men, but only at the age of 31
      (49.2 mm2 smaller among those who sit often vs rarely (95% CI -96.0 to -2.4)). No
      significant differences were detected between OPA categories and vertebral CSA
      (p>0.05). Thus, we found no consistent association between OPA and vertebral size
      among either sex. CONCLUSIONS: OPA seems to have very little effect on vertebral
      size. Our results suggest that the effect of LTPA on vertebral size is different
      to that of OPA.

PMID- 27864434
TI  - Occupational causes of amyotrophic lateral sclerosis: where to from here?

PMID- 27864436
TI  - BASHH annual conference.

PMID- 27864437
TI  - Sex and relationships education (SRE) in schools: feedback from the Sexpectations
      Project, Hastings, UK.

PMID- 27864439
TI  - Effectiveness of harm reduction education on decreasing risky-behaviour among
      injecting drug users in Egypt.

PMID- 27864438
TI  - Monitoring and assessment of bone mineral density in HIV-infected individuals.

PMID- 27864440
TI  - Clinical round-up.

PMID- 27864441
TI  - Essentials of anatomic pathology.

PMID- 27864444
TI  - Simultaneous Burst Imaging of Dual Species Using Planar Laser-Induced
      Fluorescence at 50 kHz in Turbulent Premixed Flames.
AB  - Spatially and temporally resolved measurements are of great importance in
      turbulent premixed flame studies, especially when investigating rapid processes
      such as when flame local extinction, re-ignition, or flashback occur in a
      reacting flow. Here, an experimental approach for simultaneously probing two
      different species at high frame rates (50 kHz) is presented by employing a multi
      YAG laser system. The laser radiation at 355 nm generated by a multi-YAG laser
      system was split into two beam paths: one beam for exciting formaldehyde and the
      other for pumping an optical parametric oscillator (OPO). To be able to capture
      the resulting fluorescence at such a high frame rate without significant loss in
      spatial resolution, two framing cameras, containing a total of 16 intensified
      charge-coupled devices (CCDs), were employed. In principle, the proposed setup
      provides the possibility of probing formaldehyde and simultaneously accessing the
      distribution of one other relevant species at this high frame rate. In this
      demonstration, the laser wavelength was tuned to 283 nm and, in conjunction with
      the 355 nm beam path, simultaneously high speed two-dimensional (2D)
      visualization of OH-radicals and formaldehyde was achieved. A modified flat
      flame, McKenna-type burner was used to provide a turbulent premixed jet-flame
      supported by a surrounding pilot flame. Local flame extinction and re-ignition
      processes were recorded for fuel/air jet speeds of 120 m/s.

PMID- 27864442
TI  - Two Trichome Birefringence-Like Proteins Mediate Xylan Acetylation, Which Is
      Essential for Leaf Blight Resistance in Rice.
AB  - Acetylation is a ubiquitous modification on cell wall polymers, which play a
      structural role in plant growth and stress defenses. However, the mechanisms for
      how crop plants accomplish cell wall polymer O-acetylation are largely unknown.
      Here, we report on the isolation and characterization of two trichome
      birefringence-like (tbl) mutants in rice (Oryza sativa), which are affected in
      xylan O-acetylation. ostbl1 and ostbl2 single mutant and the tbl1 tbl2 double
      mutant displayed a stunted growth phenotype with varied degree of dwarfism. As
      shown by chemical assays, the wall acetylation level is affected in the mutants
      and the knock-down and overexpression transgenic plants. Furthermore, NMR
      spectroscopy analyses showed that all those mutants have varied decreases in
      xylan monoacetylation. The divergent expression levels of OsTBL1 and OsTBL2
      explained the chemotype difference and indicated that OsTBL1 is a functionally
      dominant gene. OsTBL1 was found to be Golgi-localized. The recombinant OsTBL1
      protein incorporates acetyl groups onto xylan. By using xylopentaose, a preferred
      acceptor substrate, OsTBL1 can transfer up to four acetyl residues onto
      xylopentaose, and this activity showed saturable kinetics. 2D-NMR spectroscopy
      showed that OsTBL1 transfers acetate to both 2-O and 3-O sites of xylosyl
      residues. In addition, ostbl1 and tbl1 tbl2 displayed susceptibility to rice
      blight disease, indicating that this xylan modification is required for pathogen
      resistance. This study identifies the major genes responsible for xylan
      acetylation in rice plants.

PMID- 27864445
TI  - Comparison of Fiber Optic and Conduit Attenuated Total Reflection (ATR) Fourier
      Transform Infrared (FT-IR) Setup for In-Line Fermentation Monitoring.
AB  - The performance of a fiber optic and an optical conduit in-line attenuated total
      reflection mid-infrared (IR) probe during in situ monitoring of Penicillium
      chrysogenum fermentation were compared. The fiber optic probe was connected to a
      sealed, portable, Fourier transform infrared (FT-IR) process spectrometer via a
      plug-and-play interface. The optical conduit, on the other hand, was connected to
      a FT-IR process spectrometer via a knuckled probe with mirrors that had to be
      adjusted prior to each fermentation, which were purged with dry air. Penicillin V
      (PenV) and its precursor phenoxyacetic acid (POX) concentrations were determined
      by online high-performance liquid chromatography and the obtained concentrations
      were used as reference to build partial least squares regression models. Cross
      validated root-mean-square errors of prediction were found to be 0.2 g L-1 (POX)
      and 0.19 g L-1 (PenV) for the fiber optic setup and 0.17 g L-1 (both POX and
      PenV) for the conduit setup. Higher noise-levels and spectrum-to-spectrum
      variations of the fiber optic setup lead to higher noise of estimated (i.e.,
      unknown) POX and PenV concentrations than was found for the conduit setup. It
      seems that trade-off has to be made between ease of handling (fiber optic setup)
      and measurement accuracy (optical conduit setup) when choosing one of these
      systems for bioprocess monitoring.

PMID- 27864443
TI  - Integrative Approaches for the Identification and Localization of Specialized
      Metabolites in Tripterygium Roots.
AB  - Members of the genus Tripterygium are known to contain an astonishing diversity
      of specialized metabolites. The lack of authentic standards has been an
      impediment to the rapid identification of such metabolites in extracts. We
      employed an approach that involves the searching of multiple, complementary
      chromatographic and spectroscopic data sets against the Spektraris database to
      speed up the metabolite identification process. Mass spectrometry-based imaging
      indicated a differential localization of triterpenoids to the periderm and
      sesquiterpene alkaloids to the cortex layer of Tripterygium roots. We further
      provide evidence that triterpenoids are accumulated to high levels in cells that
      contain suberized cell walls, which might indicate a mechanism for storage. To
      our knowledge, our data provide first insights into the cell type specificity of
      metabolite accumulation in Tripterygium and set the stage for furthering our
      understanding of the biological implications of specialized metabolites in this
      genus.

PMID- 27864446
TI  - Simultaneous Imaging and Spectroscopy of Detonation Interaction in Reactive and
      Energetic Materials.
AB  - A dual framing camera system was coupled with custom-designed ultrafast imaging
      spectrometer optics to yield simultaneous imaging and imaging spectroscopy of
      extremely short detonation interaction events in reactive materials. For short
      exposures of 100 ns or less, spectral resolutions of 2.4 A are achievable,
      allowing for time-resolved identification of key intermediate species evolving
      from prompt reaction. Under some circumstances, emission can be fit to a local
      emission temperature, assuming the optically thin limit. Applications to reactive
      metal systems involving aluminum, magnesium, titanium, boron, and silicon are
      demonstrated.

PMID- 27864447
TI  - Analysis of the Thermo-Reflectivity Coefficient Influence Using Photothermal Pump
      Probe Techniques.
AB  - Recent improvements in the modeling of photo-induced thermo-optical-mechanical
      effects have broadened the application of photothermal techniques to a large
      class of solids and fluids. During laser excitation, changes in optical
      reflectivity due to temperature variation may affect the photothermal signal. In
      this study, the influence of the reflectivity change due to heating is analyzed
      for two pump-probe photothermal techniques, thermal lens and thermal mirror. A
      linear equation for the temperature dependence of the reflectivity is derived,
      and the solution is tested using optical properties of semi-transparent and
      opaque materials. For semi-transparent materials, the influence of the
      reflectivity change in photothermal signals is less than 0.01%, while for opaque
      materials it is lower than 3%.

PMID- 27864448
TI  - Evaluation of a rapid antigen test for detection of Streptococcus pneumoniae in
      cerebrospinal fluid.
AB  - Detection of Streptococcus pneumoniae antigen in cerebrospinal fluid (CSF) using
      lateral flow immunochromatography tests (ICTs) is an effective, rapid and low
      cost method to diagnose pneumococcal meningitis. This study evaluated the
      diagnostic accuracy of the Uni-Gold ICT to detect pneumococcal antigen in CSF
      specimens, compared with gold standard bacteriology and quantitative real-time
      PCR (qPCR) testing. CSF specimens (n=69) from patients with suspected bacterial
      meningitis were included in the study. 13/69 (19%) were positive and 56/69 (81%)
      were negative for pneumococcus by the gold standard tests. The ICT had
      sensitivity of 85% (55%-98%), specificity of 96% (88%-100%), positive likelihood
      ratio of 23.7 (6-94) and negative likelihood ratio of 0.16 (0.04-0.57). Overall,
      a strong correlation between the ICT and qPCR results was seen (kappa=0.81). In
      contrast, CSF microscopy and culture were exceptionally insensitive. The ICT
      method is sufficiently robust and accurate for use in algorithms to diagnose
      bacterial meningitis.

PMID- 27864449
TI  - What are the critical steps in processing blood cultures? A prospective audit
      evaluating current practice of reporting blood cultures in a centralised
      laboratory serving secondary care hospitals.
AB  - AIMS: To assess current procedures of processing positive blood cultures against
      national standards with an aim to evaluate its clinical impact and to determine
      the utility of currently available rapid identification and susceptibility tests
      in processing of blood cultures. METHODS: Blood cultures from three secondary
      care hospitals, processed at a centralised laboratory, were prospectively
      audited. Data regarding processing times, communication with prescribers, changes
      to patient management and mortality within 30 days of a significant blood culture
      were collected in a preplanned pro forma for a 4-week period. RESULTS: Of 2206
      blood cultures, 211 positive blood cultures flagged positive. Sixty-nine (3.1%)
      of all cultures were considered to be contaminated. Fifty per cent of blood
      cultures that flagged positive had a Gram stain reported within 2 hours. Two
      (0.99%) patients with a significant bacteraemia had escalation of antimicrobial
      treatment at the point of reporting the Gram stain that was subsequently deemed
      necessary once sensitivity results were known. Most common intervention was de
      escalation of therapy for Gram-positive organisms at the point of availability of
      pathogen identification (25.6% in Gram positive vs 10% in Gram negative;
      p=0.012). For Gram-negative organisms, the most common intervention was de
      escalation of therapy at the point of availability of sensitivity results (43% in
      Gram negatives vs 17.9% in Gram positive; p=0.0097). Overall mortality within 30
      days of a positive blood culture was 10.9% (23/211). Antibiotic resistance may
      have contributed to mortality in four of these patients (three Gram negative and
      one Gram positive). CONCLUSION: Gram stain result had the least impact on
      antibiotic treatment interventions (escalation or de-escalation). Tests that
      improve identification time for Gram-positive pathogens and sensitivity time for
      Gram-negative pathogens had the greatest impact in making significant changes to
      antimicrobial treatment.

PMID- 27864451
TI  - Reacquisition of E-cadherin expression in metastatic deposits of signet-ring cell
      carcinoma of the upper gastrointestinal system: a potential anchor for metastatic
      deposition.
AB  - AIMS: To examine the expression of E-cadherin in paired primary and metastatic
      signet-ring cell carcinomas (SRCC) of various organ systems in order to explore
      the potential role of the molecule in metastatic dissemination of this unique
      tumour type. METHODS: Thirty-seven consecutive cases of SRCC from various organs
      with paired primary and metastatic tumorous tissue available were retrieved. The
      intensity of membranous E-cadherin expression was semiquantitatively scored on a
      scale of 0-3+. RESULTS: Reduced E-cadherin expression was a distinct feature of
      primary SRCC and was observed in 78% of primary tumours. Interestingly, the E
      cadherin reduction was less frequently seen in metastatic SRCC when compared with
      their primary counterparts, and was only found in 57% of tumours in lymph node
      metastases or at distant sites of relapse. Furthermore, the mean score of E
      cadherin expression of primary SRCC was significantly lower than that of their
      metastatic counterparts (2.3 vs 1.8; p=0.008). When divided by organ systems, the
      reacquisition of E-cadherin expression in the metastatic deposits was most
      remarkable in the SRCC of upper gastrointestinal tract origin (2.3 vs 1.4;
      p=0.003), whereas no significant difference was observed in other organ systems.
      CONCLUSIONS: While the reduction of E-cadherin in primary SRCC supports its
      pivotal role in epithelial-mesenchymal transition, a process crucial in tumour
      progression and metastatic dissemination, the re-expression of this molecule in
      metastatic SRCC cells implies a reversal to their epithelial phenotype (thus
      mesenchymal-epithelial transition) which, in turn, theoretically helps tumour
      cells to anchor and form cohesive metastatic deposits.

PMID- 27864450
TI  - MAGE-A family expression is correlated with poor survival of patients with lung
      adenocarcinoma: a retrospective clinical study based on tissue microarray.
AB  - OBJECTIVES: As the best characterised cancer/testis antigen family members,
      melanoma-associated antigens (MAGE) have been reported to be expressed in various
      malignant tumours. However, the expression pattern of MAGE-A family in lung
      adenocarcinoma (LAC) specimens and their prognostic and therapeutic significance
      for patients with LAC is still unclear. MATERIALS AND METHODS: Tissue microarray
      based immunohistochemistry analysis was used to examine the expression of MAGE-A
      family members (including MAGE-A1, A2, A3, A4, A6, A10, A11 and A12) in 105
      paired LAC specimens and the corresponding pericarcinoma specimens. The
      association between MAGE-A expression and the clinicopathological parameters, and
      the 10-year overall survival of patients with LAC were analysed. In addition, the
      association between MAGE-A expression and the epithelial growth factor receptor
      (EGFR) amplification and ALK-EML4 rearrangements of patients with LAC were also
      analysed. RESULTS: The immunohistochemical evaluation revealed that MAGE-A family
      was expressed in 46.66% of LAC specimens, but not in the corresponding
      pericarcinoma specimens. MAGE-A expression was not associated with the
      clinicopathological factors but with worse 10-year survival, and was a poor
      prognostic marker for patients with LAC. MAGE-A expression was not correlated
      with EGFR amplification and ALK rearrangements. Interestingly, MAGE-A expression
      can affect the overall survival of patients with LAC without EGFR amplification
      or ALK rearrangements, but not affect the overall survival of patients with LAC
      and EGFR amplification or ALK rearrangements. CONCLUSIONS: Molecular assessment
      of MAGE-A family members could be considered to improve the prognostic evaluation
      and to provide a new potential therapeutic strategy for patients with LAC.

PMID- 27864452
TI  - Identifying progression predictors of breast ductal carcinoma in situ.
AB  - Ductal carcinoma in situ (DCIS) refers to neoplastic epithelial cells
      proliferating within the mammary ducts of the breast, which have not breached the
      basement membrane nor invaded surrounding tissues. Traditional thinking holds
      that DCIS represents an early step in a linear progression towards invasive
      ductal carcinoma (IDC). However, as only approximately half of DCIS cases
      progress to IDC, important questions around the key determinants of malignant
      progression need to be answered. Recent studies have revealed that molecular
      differences between DCIS and IDC cells are not found at the genomic level;
      instead, altered patterns of gene expression and post-translational regulation
      lead to distinct transcriptomic and proteomic profiles. Therefore, understanding
      malignant progression will require a different approach that takes into account
      the diverse tumour cell extrinsic factors driving changes in tumour cell gene
      expression necessary for the invasive phenotype. Here, we review the roles of the
      tumour stroma (including mesenchymal cells, immune cells and the extracellular
      matrix) and myoepithelial cells in malignant progression and make a case for a
      more integrated approach to the study and assessment of DCIS and its progression,
      or lack thereof, to invasive disease.

PMID- 27864453
TI  - Glial cells and energy balance.
AB  - The search for new strategies and drugs to abate the current obesity epidemic has
      led to the intensification of research aimed at understanding the neuroendocrine
      control of appetite and energy expenditure. This intensified investigation of
      metabolic control has also included the study of how glial cells participate in
      this process. Glia, the most abundant cell type in the central nervous system,
      perform a wide spectrum of functions and are vital for the correct functioning of
      neurons and neuronal circuits. Current evidence indicates that hypothalamic glia,
      in particular astrocytes, tanycytes and microglia, are involved in both
      physiological and pathophysiological mechanisms of appetite and metabolic
      control, at least in part by regulating the signals reaching metabolic neuronal
      circuits. Glia transport nutrients, hormones and neurotransmitters; they secrete
      growth factors, hormones, cytokines and gliotransmitters and are a source of
      neuroprogenitor cells. These functions are regulated, as glia also respond to
      numerous hormones and nutrients, with the lack of specific hormonal signaling in
      hypothalamic astrocytes disrupting metabolic homeostasis. Here, we review some of
      the more recent advances in the role of glial cells in metabolic control, with a
      special emphasis on the differences between glial cell responses in males and
      females.

PMID- 27864454
TI  - Minimal Medial Injury After Orbital Atherectomy.

PMID- 27864455
TI  - Commentary: Internal Iliac Artery Embolization During EVAR.

PMID- 27864456
TI  - Endovascular Treatment of Common Iliac Artery Aneurysms With an Iliac Branch
      Device: Multicenter Experience of 140 Patients.
AB  - PURPOSE: To evaluate the efficacy, feasibility, and long-term outcomes of the
      Zenith ZBIS iliac branch device (IBD) to preserve internal iliac artery (IIA)
      perfusion in a large Dutch multicenter cohort. METHODS: Between September 2004
      and August 2015, 140 patients (mean age 70.9+/-7.4 years; 130 men) with 162 IBD
      implantations were identified in 7 vascular centers. The indication for IBD
      implantation was an abdominal aortic aneurysm >55 mm with a concomitant common
      iliac artery (CIA) aneurysm >20 mm (n=40), a CIA aneurysm with a diameter >30 mm
      (n=89), or revision of a type Ib endoleak after endovascular aneurysm repair
      (n=11). RESULTS: Technical success (aneurysm exclusion, no type I or III
      endoleak, and a patent IIA) was obtained in 157 (96.9%) of 162 IBD implantations.
      Six (4.3%) patients developed major complications; 2 (1.4%) died. Mean follow-up
      was 26.6+/-24.1 months, during which 17 (12.1%) IBD-associated secondary
      interventions were performed. Including technical failures and intentional IIA
      embolizations, 15 (9.3%) IIA branch occlusions were identified; buttock
      claudication developed in 6 of these patients. The freedom from secondary
      intervention estimate was 75.9% (95% confidence interval 59.7 to 86.3) at 5
      years. CONCLUSION: CIA aneurysms can be treated safely and effectively by IBDs
      with preservation of antegrade flow to the IIA. Secondary interventions are
      indicated in >10% of patients during follow-up but can be performed
      endovascularly in most.

PMID- 27864457
TI  - Embolization or Simple Coverage to Exclude the Internal Iliac Artery During
      Endovascular Repair of Aortoiliac Aneurysms? Systematic Review and Meta-analysis
      of Comparative Studies.
AB  - PURPOSE: To compare results of simple coverage vs preemptive embolization to
      exclude the internal iliac artery (IIA) during endovascular repair of aortoiliac
      aneurysms. METHODS: A systematic review of the literature was conducted by
      searching MEDLINE, CENTRAL, and OpenGray databases until March 2016. Primary
      outcome measures were safety and efficacy of the 2 strategies. Safety was
      determined by 30-day mortality and the minor and major complication rates.
      Efficacy was determined by absence of endoleak from the target IIA. Secondary
      outcomes of any endoleak, reintervention, operative time, fluoroscopy time, blood
      loss, contrast volume, and length of hospitalization were also examined. 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 interval (CI). Forest plots and inconsistency ( I2)
      statistics were used to evaluate the heterogeneity of the included studies.
      RESULTS: Eight observational studies were included in the analysis. Overall, 284
      and 255 subjects underwent IIA coverage or embolization, respectively. IIA
      coverage resulted in a significantly lower major complication rate (6% vs 29%; OR
      2.97, 95% CI 1.46 to 6.04, p=0.003; I2=0%) and shorter hospitalization (MD 0.48
      days, 95% CI 0.08 to 0.89, p=0.02; I2=0%), while differences in all other
      outcomes were not statistically significant. CONCLUSION: In the presence of
      limited data, available evidence suggests that simple coverage of the IIA may
      result in significantly fewer major complications compared to preemptive
      embolization; at the same time, the rates of endoleaks and/or reinterventions are
      similar between groups.

PMID- 27864458
TI  - Three-Dimensional Analysis of Component Stability of the Nellix Endovascular
      Aneurysm Sealing System After Treatment of Infrarenal Abdominal Aortic Aneurysms.
AB  - PURPOSE: To assess short-term stability and conformational changes of the Nellix
      EndoVascular Aneurysm Sealing (EVAS) System using 3-dimensional (3D) analysis.
      METHODS: Postoperative computed tomography (CT) scans obtained at 0, 3, and 12
      months in 24 patients (mean age 75+/-7 years; 22 men) who underwent EVAS between
      December 2013 and December 2014 for intact abdominal aortic aneurysm (within the
      instructions for use) were evaluated for stent-graft deviation in multiple planes
      using dedicated 3D analysis software. In addition, 2D analysis using an
      anatomically fixed reference landmark was performed to assess craniocaudal
      migration. Clinical and follow-up data of the patients were recorded and matched
      with results of the imaging analysis. RESULTS: Overall stability of the Nellix
      endografts was promising. Relevant conformational changes in the majority of
      cases were limited to the iliac graft segment and were clinically benign in all
      cases. Conversely, the only deviation of the proximal stent-graft segment was
      found in a patient with type Ia endoleak. Additional 2D analysis found relevant
      (>=5 mm) caudal migration of the Nellix stent-graft in 6 patients, including the
      one with the type Ia endoleak. In 3 patients, 3D analysis demonstrated the
      absence of relevant conformational changes of the endografts despite caudal
      migration. CONCLUSION: Overall stability of the separate EVAS stent-grafts is
      promising in the short term. Relevant conformational changes (stent-graft
      deviation) in the majority of cases were benign and confined to the iliac
      segment.

PMID- 27864459
TI  - Feasibility and Technical Aspects of Proximal Nellix-in-Nellix Extension for Late
      Caudal Endograft Migration.
AB  - PURPOSE: To describe the feasibility and technical aspects of a proximal Nellix
      in-Nellix extension to treat caudal stent-graft migration after endovascular
      aneurysm sealing (EVAS) in the in vitro and in vivo settings. METHODS: In vitro
      studies were designed (1) to assess inner diameters of Nellix-in-Nellix
      extensions after postdilation with 12-mm balloons and (2) to test wall apposition
      in tubes with different diameters using a Nellix-in-Nellix stent-graft that
      extended out of the original Nellix stent-graft lumen by 10, 20, 30, and 40 mm.
      Simulated-use experiments were performed using silicone models in conjunction
      with a pulsatile flow pump. In the clinical setting, 5 patients (median age 74
      years, range 73-83) presented at 2 centers with type Ia endoleak secondary to
      caudal Nellix stent-graft migration measuring a median 9 mm (range 7-15) on the
      left and 7 mm (range 0-11) on the right. Median polymer fill volume at the
      initial EVAS procedure was 42.5 mL (range 25-71). The median time to
      reintervention with a proximal Nellix extension was 15 months (range 13-32).
      RESULTS: In vitro, the inner diameters of the Nellix-in-Nellix extensions were
      consistent after postdilation. Cases with 10 and 20 mm of exposed endobag
      resulted in a poor seal with endoleak, while cases with 30 and 40 mm of exposed
      endobag length exhibited angiographic seal. Fill line pressures of the second
      Nellix were higher than expected. In the 5 clinical cases, chimney grafts were
      required in each case to create an adequate proximal landing zone. The Nellix-in
      Nellix procedure was successful in all patients. There were no procedure-related
      complications, and no endoleaks were observed during a median 12-month follow-up.
      Reinterventions were performed in 2 patients because of in-stent stenosis and
      chimney graft compression, respectively. CONCLUSION: Proximal Nellix-in-Nellix
      extension can be used to treat caudally migrated Nellix stent-grafts and to treat
      the consequent type Ia endoleak, but the technique differs from primary EVAS. The
      development of dedicated proximal extensions is desirable.

PMID- 27864460
TI  - Use of the Octopus Endograft Technique to Reconstruct Renovisceral Arteries
      Arising From the False Lumen of a Rapidly Expanding Type B Aortic Dissection
      After Endovascular Repair.
AB  - PURPOSE: To describe the use and 6-month outcomes of the octopus endograft
      technique to reconstruct renovisceral arteries arising from the false lumen (FL)
      of a type B aortic dissection after thoracic endovascular aortic repair (TEVAR).
      CASE REPORT: A 46-year-old man post TEVAR for type B aortic dissection was
      admitted with persistent back pain and a rapidly expanding residual dissection.
      The celiac and left renal arteries arose from the FL and the superior mesenteric
      artery from both lumens, with the FL as its main supply. A 20% oversized Endurant
      stent-graft was deployed with the short limb just above the beginning of the
      dissection flap and the long limb in the aortic true lumen. A 120-mm-long
      Endurant extended limb was delivered antegradely via a conduit and deployed into
      the FL, with a 3-cm overlap with the short limb of the Endurant main body. The 3
      renovisceral arteries were reconstructed by lining each with a series of Viabahn
      or Fluency stent-grafts whose proximal ends were subsequently placed parallel in
      the FL Endurant extended limb and dilated with kissing balloons. Imaging at 6
      months showed an excluded FL, without stenosis or occlusion in the stent-graft or
      the renovisceral arteries. CONCLUSION: This case illustrates the successful use
      of the octopus endograft technique to reconstruct renovisceral arteries arising
      from a rapidly expanding FL in a post-TEVAR type B aortic dissection; the
      technique might be applicable in carefully selected patients.

PMID- 27864461
TI  - Commentary: Endovascular Repair of Postdissection Aneurysms Involving the
      Thoracoabdominal Aorta.

PMID- 27864462
TI  - Collateral status and tissue outcome after intra-arterial therapy for patients
      with acute ischemic stroke.
AB  - Intra-arterial therapy (IAT) for ischemic stroke aims to save brain tissue.
      Collaterals are thought to contribute to prolonged penumbra sustenance. In this
      study, we investigate the effect of collateral status on brain tissue salvage
      with IAT. In 500 patients randomized between IAT and standard care, collateral
      status was graded from 0 (absent) to 3 (good). Final infarct volumes (FIV) were
      calculated on post-treatment CT. FIVs were compared between treatment groups per
      collateral grade. Multivariable linear regression with interaction terms was
      performed to study whether collaterals modified IAT effect on FIV. Four-hundred
      forty-nine patients were included in the analysis. Median FIV for the IAT group
      was significantly lower with 54.5 mL (95% IQR: 21.8-145.0) than for the controls
      with 81.8 mL (95% IQR: 40.0-154.0) ( p = 0.020). Treatment effect differed across
      collateral grades, although there was no significant interaction (unadjusted p =
      0.054; adjusted p = 0.105). For grade 3, IAT resulted in a FIV reduction of 30.1
      mL ( p = 0.024). For grade 2 and 1, this difference was, respectively, 28.4 mL (
      p = 0.028) and 28.4 mL ( p = 0.29). For grade 0, this was 88.6 mL ( p = 0.28) in
      favour of controls. IAT saves substantially more brain tissue as compared to
      standard care. We observed a trend of increasing effect of IAT with higher
      collateral grades.

PMID- 27864463
TI  - Increased brain hemopexin levels improve outcomes after intracerebral hemorrhage.
AB  - Following intracerebral hemorrhage (ICH), extracellular heme precipitates
      secondary brain injury, which results in irreversible brain damage and enduring
      neurological deficits. Hemopexin (Hpx) is an endogenous protein responsible for
      scavenging heme, thereby modulating its intrinsic proxidant/proinflammatory
      properties. Although Hpx is present in the brain, the endogenous levels are
      insufficient to combat the massive heme overload following ICH. We hypothesized
      that increasing brain Hpx levels would improve ICH outcomes. Unique recombinant
      adeno-associated viral vectors were designed to specifically overexpress Hpx
      within the mouse brain. Western blotting, ELISA, and immunohistochemistry of
      brain homogenates/sections, CSF, and serum were performed. As compared to
      controls, Hpx mice have increased Hpx protein levels in all three types of
      biospecimens evaluated, which results in 45.6 +/- 6.9% smaller lesions and
      improved functional recovery after ICH (n=14-19/group, p < 0.05). Local
      mechanistic analyses show significantly less tissue injury, trends toward smaller
      hematoma volumes, unchanged heme oxygenase 1 and iron levels, and significantly
      increased microgliosis and decreased astrogliosis and lipid peroxidation.
      Peripheral levels of heme-related markers indicate a positive modulation of iron
      binding capacity. These findings reveal that high local Hpx levels improve ICH
      outcomes, likely through both central and peripheral clearance mechanisms, and
      establish the potential for therapeutically administering clinical-grade Hpx for
      ICH.

PMID- 27864464
TI  - Inhibition of stress fiber formation preserves blood-brain barrier after
      intracerebral hemorrhage in mice.
AB  - Intracerebral hemorrhage (ICH) represents the deadliest subtype of all strokes.
      The development of brain edema, a consequence of blood-brain barrier (BBB)
      disruption, is the most life-threatening event after ICH. Pathophysiological
      conditions activate the endothelium, one of the components of BBB, inducing
      rearrangement of the actin cytoskeleton. Upon activation, globular actin
      assembles into a filamentous actin resulting in the formation of contractile
      actin bundles, stress fibers. The contraction of stress fibers leads to the
      formation of intercellular gaps between endothelial cells increasing the
      permeability of BBB. In the present study, we investigated the effect of ICH on
      stress fiber formation in CD1 mice. We hypothesized that ICH-induced formation of
      stress fiber is triggered by the activation of PDGFR-beta and mediated by the
      cortactin/RhoA/LIMK pathway. We demonstrated that ICH induces formation of stress
      fibers. Furthermore, we demonstrated that the inhibition of PDGFR-beta and its
      downstream reduced the number of stress fibers, preserving BBB and resulting in
      the amelioration of brain edema and improvement of neurological functions in mice
      after ICH.

PMID- 27864465
TI  - Posttraumatic therapeutic hypothermia alters microglial and macrophage
      polarization toward a beneficial phenotype.
AB  - Posttraumatic inflammatory processes contribute to pathological and reparative
      processes observed after traumatic brain injury (TBI). Recent findings have
      emphasized that these divergent effects result from subsets of proinflammatory
      (M1) or anti-inflammatory (M2) microglia and macrophages. Therapeutic hypothermia
      has been tested in preclinical and clinical models of TBI to limit secondary
      injury mechanisms including proinflammatory processes. This study evaluated the
      effects of posttraumatic hypothermia (PTH) on phenotype patterns of
      microglia/macrophages. Sprague-Dawley rats underwent moderate fluid percussion
      brain injury with normothermia (37C) or hypothermia (33C). Cortical and
      hippocampal regions were analyzed using flow cytometry and reverse transcription
      polymerase chain reaction (RT-PCR) at several periods after injury. Compared to
      normothermia, PTH attenuated infiltrating cortical macrophages positive for
      CD11b+ and CD45high. At 24 h, the ratio of iNOS+ (M1) to arginase+ (M2) cells
      after hypothermia showed a decrease compared to normothermia. RT-PCR of M1
      associated genes including iNOS and IL-1beta was significantly reduced with
      hypothermia while M2-associated genes including arginase and CD163 were
      significantly increased compared to normothermic conditions. The injury-induced
      increased expression of the chemokine Ccl2 was also reduced with PTH. These
      studies provide a link between temperature-sensitive alterations in
      macrophage/microglia activation and polarization toward a M2 phenotype that could
      be permissive for cell survival and repair.

PMID- 27864466
TI  - Thiamet G mediates neuroprotection in experimental stroke by modulating
      microglia/macrophage polarization and inhibiting NF-kappaB p65 signaling.
AB  - Inflammatory responses are accountable for secondary injury induced by acute
      ischemic stroke (AIS). Previous studies indicated that O-GlcNAc modification (O
      GlcNAcylation) is involved in the pathology of AIS, and increase of O
      GlcNAcylation by glucosamine attenuated the brain damage after
      ischemia/reperfusion. Inhibition of beta-N-acetylglucosaminidase (OGA) with
      thiamet G (TMG) is an alternative option for accumulating O-GlcNAcylated
      proteins. In this study, we investigate the neuroprotective effect of TMG in a
      mouse model of experimental stroke. Our results indicate that TMG administration
      either before or after middle cerebral artery occlusion (MCAO) surgery
      dramatically reduced infarct volume compared with that in untreated controls. TMG
      treatment ameliorated the neurological deficits and improved clinical outcomes in
      neurobehavioral tests by modulating the expression of pro-inflammatory and anti
      inflammatory cytokines. Additionally, TMG administration reduced the number of
      Iba1+ cells in MCAO mice, decreased expression of the M1 markers, and increased
      expression of the M2 markers in vivo. In vitro, M1 polarization of BV2 cells was
      inhibited by TMG treatment. Moreover, TMG decreased the expression of iNOS and
      COX2 mainly by suppressing NF-kappaB p65 signaling. These results suggest that
      TMG exerts a neuroprotective effect and could be useful as an anti-inflammatory
      agent for ischemic stroke therapy.

PMID- 27864468
TI  - Response to the Letter to the Editor: "Factors Influencing Early Dental Implant
      Failures"

PMID- 27864469
TI  - Letter to the Editor: "Factors Influencing Early Dental Implant Failures"

PMID- 27864467
TI  - Human dendritic cells (DCs) are derived from distinct circulating precursors that
      are precommitted to become CD1c+ or CD141+ DCs.
AB  - In humans, conventional dendritic cells (cDCs) exist as two unique populations
      characterized by expression of CD1c and CD141. cDCs arise from increasingly
      restricted but well-defined bone marrow progenitors that include the common DC
      progenitor that differentiates into the pre-cDC, which is the direct precursor of
      cDCs. In this study, we show that pre-cDCs in humans are heterogeneous,
      consisting of two distinct populations of precursors that are precommitted to
      become either CD1c+ or CD141+ cDCs. The two groups of lineage-primed precursors
      can be distinguished based on differential expression of CD172a. Both
      subpopulations of pre-cDCs arise in the adult bone marrow and can be found in
      cord blood and adult peripheral blood. Gene expression analysis revealed that
      CD172a+ and CD172a- pre-cDCs represent developmentally discrete populations that
      differentially express lineage-restricted transcription factors. A clinical trial
      of Flt3L injection revealed that this cytokine increases the number of both
      CD172a- and CD172a+ pre-cDCs in human peripheral blood.

PMID- 27864470
TI  - Percutaneous Pulmonary Valve Implantation in the Native Right Ventricular Outflow
      Tract Using a 29-mm Edwards SAPIEN 3 Valve.
AB  - Percutaneous pulmonary valve implantation is now an acceptable treatment option.
      The Edwards SAPIEN valve, intended for transcatheter aortic valve implantation,
      has been used in patients whose landing zone diameter is >22 to 24 mm which is
      not suitable for Melody valve. We report a patient in whom we successfully placed
      the latest generation, Edwards SAPIEN 3 (ES3) in the pulmonary position. However,
      because of the short covered portion of this valve, there was a significant
      paravalvular leak through the stent struts requiring implantation of a second ES3
      valve.

PMID- 27864471
TI  - Structuring Process Evaluation to Forecast Use and Sustainability of an
      Intervention: Theory and Data From the Efficacy Trial for Lunch Is in the Bag.
AB  - BACKGROUND: A cluster-randomized trial at 30 early care and education centers
      (Intervention = 15, waitlist Control = 15) showed the Lunch Is in the Bag
      intervention increased parents' packing of fruits, vegetables, and whole grains
      in their preschool children's bag lunches (parent-child dyads = 351 Intervention,
      282 Control). PURPOSE: To examine the utility of structuring the trial's process
      evaluation to forecast use, sustainability, and readiness of the intervention for
      wider dissemination and implementation. METHOD: Pretrial, the research team
      simulated user experience to forecast use of the intervention. Multiattribute
      evaluation of user experience measured during the trial assessed use and
      sustainability of the intervention. Thematic analysis of posttrial interviews
      with users evaluated sustained use and readiness for wider dissemination.
      RESULTS: Moderate use was forecast by the research team. Multiattribute
      evaluation of activity logs, surveys, and observations during the trial indicated
      use consistent with the forecast except that prevalence of parents reading the
      newsletters was greater (83% vs. 50%) and hearing their children talk about the
      classroom was less (4% vs. 50%) than forecast. Early care and education center
      level likelihood of sustained use was projected to be near zero. Posttrial
      interviews indicated use was sustained at zero centers. DISCUSSION: Structuring
      the efficacy trial's process evaluation as a progression of assessments of user
      experience produced generally accurate forecasts of use and sustainability of the
      intervention at the trial sites. CONCLUSION: This approach can assist
      interpretation of trial outcomes, aid decisions about dissemination of the
      intervention, and contribute to translational science for improving health.

PMID- 27864473
TI  - A recommendation for timing of repeat Chlamydia trachomatis test following
      infection and treatment in pregnant and nonpregnant women.
AB  - The objective of this study was to describe the time required to obtain a
      negative chlamydia test in pregnant and nonpregnant women following treatment to
      inform test-of-cure collection and recommend an abstinence period to avoid
      reinfection. Seventy-two women with Chlamydia trachomatis infection, 36 pregnant
      and 36 nonpregnant, were enrolled in a prospective cohort study. Women were
      excluded less than 18 years of age, if they had been treated for chlamydia,
      reported an allergy to macrolide antibiotics, or if they had Myasthenia Gravis.
      Women were treated for chlamydia with single-dose therapy and submitted weekly
      vaginal chlamydia nucleic acid amplification tests (NAATs). Once NAAT were
      negative, the participants completed the study. Forty-seven women completed the
      study per protocol. The primary outcome was to determine the time to a negative
      chlamydia NAAT following treatment, with secondary outcomes of determining the
      appropriate time to collect a test-of-cure following chlamydia treatment and to
      recommend an appropriate abstinence period following treatment to avoid
      reinfection. Results showed that the time to a negative chlamydia NAAT was
      significantly different between groups (log-rank p = 0.0013). The median number
      of days to obtain a negative chlamydia NAAT was 8 days (IQR 7-14) in pregnant and
      7 days (IQR 6-10) in nonpregnant women (WRST p = 0.04). All participants had a
      negative chlamydia NAAT by day 29 post-treatment. Following single-dose treatment
      for chlamydia, both pregnant and nonpregnant women should test negative with NAAT
      by 30 days post-treatment. Clinicians should collect a test-of-cure in pregnant
      women no earlier than 1 month. To avoid reinfection, women should avoid
      condomless intercourse for at least 1 month.

PMID- 27864472
TI  - Transcriptome-wide identification of NMD-targeted human mRNAs reveals extensive
      redundancy between SMG6- and SMG7-mediated degradation pathways.
AB  - Besides degrading aberrant mRNAs that harbor a premature translation termination
      codon (PTC), nonsense-mediated mRNA decay (NMD) also targets many seemingly
      "normal" mRNAs that encode for full-length proteins. To identify a bona fide set
      of such endogenous NMD targets in human cells, we applied a meta-analysis
      approach in which we combined transcriptome profiling of knockdowns and rescues
      of the three NMD factors UPF1, SMG6, and SMG7. We provide evidence that this
      combinatorial approach identifies NMD-targeted transcripts more reliably than
      previous attempts that focused on inactivation of single NMD factors. Our data
      revealed that SMG6 and SMG7 act on essentially the same transcripts, indicating
      extensive redundancy between the endo- and exonucleolytic decay routes. Besides
      mRNAs, we also identified as NMD targets many long noncoding RNAs as well as
      miRNA and snoRNA host genes. The NMD target feature with the most predictive
      value is an intron in the 3' UTR, followed by the presence of upstream open
      reading frames (uORFs) and long 3' UTRs. Furthermore, the 3' UTRs of NMD-targeted
      transcripts tend to have an increased GC content and to be phylogenetically less
      conserved when compared to 3' UTRs of NMD insensitive transcripts.

PMID- 27864474
TI  - Complement Component 3 Regulates IFN-alpha Production by Plasmacytoid Dendritic
      Cells following TLR7 Activation by a Plant Virus-like Nanoparticle.
AB  - The increasing use of plant viruses for the development of new vaccines and
      immunotherapy approaches poses questions regarding the mechanism by which the
      mammalian immune system recognizes these viruses. For example, although natural
      Abs (NA) and complement are key components of the innate immune system involved
      in the opsonization, phagocytosis, and destruction of microorganisms infecting
      mammals, their implication in plant virus recognition and immunogenicity is not
      well defined. In this study, we address the involvement of NA and the complement
      system in the activation of innate immunity through engagement of TLR7 with
      papaya mosaic virus (PapMV)-like nanoparticles. We demonstrate that NA, although
      binding to PapMV, are not involved in its recognition by the immune system. On
      the other hand, C3 strongly binds to PapMV nanoparticles and its depletion
      significantly reduces PapMV's interaction with immune cells. Unexpectedly,
      however, we observed increased immune cell activation following administration of
      PapMV to complement-depleted mice. TLR7 activation by PapMV in the absence of C3
      induced higher IFN-alpha production, resulting in superior immune cell activation
      and increased immunotherapeutic properties. In conclusion, in this study we
      established the involvement of the complement system in the recognition and the
      phagocytosis of PapMV nanoparticles and identified an unsuspected role for C3 in
      regulating the production of IFN-alpha following TLR7 activation.

PMID- 27864475
TI  - IL-17-Producing Innate and Pathogen-Specific Tissue Resident Memory gammadelta T
      Cells Expand in the Lungs of Bordetella pertussis-Infected Mice.
AB  - gammadelta T cells play a role in protective immunity to infection at mucosal
      surface, but also mediate pathology in certain autoimmune diseases through innate
      IL-17 production. Recent reports have suggested that gammadelta T cells can have
      memory analogous to conventional alphabeta T cells. In this study we have
      examined the role of gammadelta T cells in immunity to the respiratory pathogen
      Bordetella pertussis gammadelta T cells, predominantly Vgamma4-gamma1- cells,
      produced IL-17 in the lungs as early as 2 h after infection. The bacterial burden
      during primary infection was significantly enhanced and the induction of
      antimicrobial peptides was reduced in the absence of early IL-17. A second peak
      of gammadelta T cells is detected in the lungs 7-14 d after challenge and these
      gammadelta T cells were pathogen specific. gammadelta T cells, exclusively
      Vgamma4, from the lungs of infected but not naive mice produced IL-17 in response
      to heat-killed B. pertussis in the presence of APC. Furthermore, gammadelta T
      cells from the lungs of mice reinfected with B. pertussis produced significantly
      more IL-17 than gammadelta T cells from infected unprimed mice. gammadelta T
      cells with a tissue resident memory T cell phenotype (CD69+CD103+) were expanded
      in the lungs during infection with B. pertussis and proliferated rapidly after
      rechallenge of convalescent mice. Our findings demonstrate that lung gammadelta T
      cells provide an early source of innate IL-17, which promotes antimicrobial
      peptide production, whereas pathogen-specific Vgamma4 cells function in adaptive
      immunological memory against B. pertussis.

PMID- 27864476
TI  - Anti-Hinge Antibodies Recognize IgG Subclass- and Protease-Restricted
      Neoepitopes.
AB  - Anti-hinge Abs (AHAs) target neoepitopes exposed after proteolytic cleavage of
      IgG. In this study, we explored the diversity of protease- and IgG subclass
      restricted AHAs and their potential as immunological markers in healthy donors
      (HDs) and patients with rheumatoid arthritis (RA) or systemic lupus erythematosus
      (SLE). AHA reactivity against IgG-degrading enzyme of Streptococcus pyogenes
      (IdeS)- or pepsin-generated F(ab')2 fragments of all four human IgG subclasses
      was determined. AHA reactivity against one or more out of eight F(ab')2 targets
      was found in 68% (68 of 100) of HDs, 69% (68 of 99) of SLE patients, and 81% (79
      of 97) of RA patients. Specific recognition of hinge epitopes was dependent on
      IgG subclass and protease used to create the F(ab')2 targets, as confirmed by
      inhibition experiments with F(ab')2 fragments and hinge peptides. Reactivity
      against IdeS-generated F(ab')2 targets was found most frequently, whereas
      reactivity against pepsin-generated F(ab')2 targets better discriminated between
      RA and HDs or SLE, with significantly higher AHA levels against IgG1/3/4. In
      contrast, AHA levels against pepsin-cleaved IgG2 were comparable. No reactivity
      against IdeS-generated IgG2-F(ab')2s was detected. The most discriminatory AHA
      reactivity in RA was against pepsin-cleaved IgG4, with a 35% prevalence, >=5.8
      fold higher than in HDs/SLE, and significantly higher levels (p < 0.0001). Cross
      reactivity for F(ab')2s generated from different IgG subclasses was only observed
      for subclasses having homologous F(ab')2 C termini (IgG1/3/4). For IgG2, two
      pepsin cleavage sites were identified; anti-hinge reactivity was restricted to
      only one of these. In conclusion, AHAs specifically recognize IgG subclass- and
      protease-restricted hinge neoepitopes. Their protease-restricted specificity
      suggests that different AHA responses developed under distinct inflammatory or
      infectious conditions and may be markers of, and participants in, such processes.

PMID- 27864477
TI  - Is visceral flow during intra-aortic balloon pumping size or volume dependent?
AB  - AIM: We evaluated the influence of intra-aortic balloon size and volume on
      mesenteric and renal flows. METHODS: Thirty healthy swine underwent 120-minute
      ligation of the left anterior descending coronary artery followed by 6 hours of
      reperfusion. Then, they were randomly assigned to the following five groups of
      animals, with six animals in each group: no intra-aortic balloon pump (IABP), a
      short 35-mL IABP, a short 40-mL IABP, a long 35-mL IABP and a long 40-mL IABP.
      Superior mesenteric artery (SMA) and renal flows were measured at baseline (t0),
      at 2-hour ischemia (t1) and every hour thereafter until 6 hours of reperfusion
      (from tR1 to tR6). RESULTS: SMA flows increased significantly at tR1 only in the
      two short IABP groups (p<0.001) and balloon volume did not appear to affect flows
      which, at any experimental time-point, were comparable using 35 mL or 40 mL
      balloons (p>0.05). Renal flows appeared to be influenced by balloon length, but
      not by volume. Indeed, flows in the renal arteries rose during IABP treatment;
      the increase was significantly higher in the short balloon groups and throughout
      the whole reperfusion (all, p<0.001). CONCLUSIONS: Changes in visceral perfusion
      during IABP assistance were significantly related to balloon length, but not to
      its volume. This could be relevant for the evolution of balloon engineering
      design in order to reduce the incidence of mesenteric ischemia following IABP.
      Further research is necessary to confirm these findings.

PMID- 27864478
TI  - Patient and Caregiver Interplay in Behavioral and Psychological Symptoms of
      Dementia: Family Caregiver's Experience.
AB  - The purpose of this study was to identify family caregivers' experiences in
      managing the behavioral and psychological symptoms of dementia (BPSD) with
      particular focus on their interpersonal interactions with patient with dementia.
      Data were collected through focus-group interviews with 15 family caregivers from
      three local dementia-support centers located in Seoul. Data were analyzed using
      content analysis. Three main themes were identified through data analysis:
      triggers of BPSD, family caregiver's actions in response to BPSD and patient's
      reactions, and the effect of BPSD on family caregivers. Findings demonstrated
      that BPSD depended on the complex interplay of family caregivers and patients,
      including their interaction style. This information could help nurses when
      counseling and educating family caregivers to improve or modify their attitudes
      and approaches to behavioral symptoms of patients.

PMID- 27864479
TI  - Epicardial adipose tissue and cardiovascular outcome in patients with acute
      coronary syndrome undergoing percutaneous coronary intervention.
AB  - AIMS: We investigated the association between epicardial adipose tissue (EAT)
      thickness and cardiovascular outcomes in a cohort of high-risk patients with
      acute coronary syndrome undergoing percutaneous coronary intervention. METHODS:
      Of 1198 patients undergoing percutaneous coronary intervention, transthoracic
      echocardiography was performed in 438 patients during the index hospitalization.
      EAT thickness was measured in the parasternal long-axis view perpendicularly on
      the free wall of the right ventricle at end-systole in three consecutive cardiac
      cycles and then averaged. As the primary outcome measure, a composite of major
      adverse cardiovascular events - including cardiovascular death, non-fatal
      myocardial infarction and non-fatal stroke - was investigated after three years
      of follow-up. RESULTS: Patients were included between 2004 and 2012 and 293
      (66.9%) were men. The median EAT thickness was 2.65 mm (interquartile range 2.00
      3.00). EAT was correlated with body mass index ( R=0.404; p<0.001), weight (
      R=0.314; p<0.001), baseline creatinine ( R=0.118; p=0.014) and baseline glucose (
      R=0.129; p=0.007). After a follow-up period of three years, a major adverse
      cardiovascular event occurred in 64 patients (14.6%) corresponding to 36 (8.2%)
      with cardiovascular death, 21 (4.8%) with myocardial infarction and seven (1.6%)
      with stroke. Regarding the primary endpoint, EAT thickness revealed a significant
      predictive effect on univariate Cox regression (hazards ratio 1.479, 95% CI 1.192
      1.953; p=0.006) and multivariate Cox regression analysis (hazards ratio 1.524,
      95% CI 1.011-2.267; p=0.038) after adjusting for established cardiovascular
      confounders. CONCLUSIONS: In a cohort of high-risk patients with acute coronary
      syndrome undergoing percutaneous coronary intervention, EAT was associated with
      established markers of cardiovascular death and had a predictive value for the
      three-year cardiovascular outcome.

PMID- 27864480
TI  - Racial and Ethnic Disparities in Infant Mortality in North Carolina, 2008-2009.
AB  - BACKGROUND: This study was designed to investigate whether racial and ethnic
      disparities in infant mortality still exist in North Carolina and to examine
      predictors of infant mortality using the North Carolina Vital Statistics
      Dataverse. METHODS: This was a retrospective, cross-sectional, observational
      study that included all 257,543 births in North Carolina in 2008-2009. Infant
      mortality was assessed based on birth records included in the database. Infant
      births and deaths were summarized by demographic and maternal/infant
      characteristics. A multivariate logistic regression model was constructed to
      jointly assess predictors of infant mortality. RESULTS: The overall infant
      mortality rate in North Carolina was 0.8%. Adjusting for confounders through the
      construction and assessment of a multivariate logistic regression model,
      statistically significant associations were found between infant mortality and
      each of the following: maternal race (both black and 'other' versus white),
      infant sex, both premature and preterm gestation (versus full term), birth weight
      (both low and high versus normal), maternal education (both less than high school
      graduate and more than high school versus college graduate), prenatal care (both
      intermediate and inadequate versus adequate), and maternal tobacco use.
      LIMITATIONS: Maternal race was limited to white, black, and other. Data on
      socioeconomic status, maternal medical risk factors, and quality of prenatal care
      were not available. At the time of the analysis, data for years beyond 2009 were
      limited. CONCLUSIONS: Racial disparities in infant mortality persist in North
      Carolina; specifically, infants of nonwhite mothers have a higher mortality rate
      than do infants of white mothers. Other factors that continue to play a
      significant role in infant mortality in North Carolina include preterm and
      premature births, male infant sex, low birth weight, maternal education less than
      college graduate, maternal tobacco use, and less than adequate prenatal care.

PMID- 27864481
TI  - Meaningful Use in Chronic Care: Improved Diabetes Outcomes Using a Primary Care
      Extension Center Model.
AB  - BACKGROUND: The effect of practice facilitation that provides onsite quality
      improvement (QI) and electronic health record (EHR) coaching on chronic care
      outcomes is unclear. This study evaluates the effectiveness of such a program
      similar to an agricultural extension center model-that provides these services.
      METHODS: Through the Health Information Technology for Economic and Clinical
      Health (HITECH) portion of the American Recovery and Reinvestment Act, the North
      Carolina Area Health Education Centers program became the Regional Extension
      Center for Health Information Technology (REC) for North Carolina. The REC
      program provides onsite technical assistance to help small primary care practices
      achieve meaningful use of certified EHRs. While pursuing meaningful use
      functionality, practices were also offered complementary onsite advice regarding
      QI issues. We followed the first 50 primary care practices that utilized both EHR
      and QI advice targeting diabetes care. RESULTS: The achievement of meaningful use
      of certified EHRs and performance of QI with onsite practice facilitation showed
      an absolute improvement of 19% in the proportion of patients who achieved
      excellent diabetes control (hemoglobin A1c < 7%) compared to baseline. In
      addition, the percentages of patients with poorly controlled diabetes (hemoglobin
      A1c > 9%) fell steeply in these practices. LIMITATIONS: No control group was
      available for comparison. CONCLUSION: Practice facilitation that provided EHR and
      QI coaching support showed important improvements in diabetes outcomes in
      practices that achieved meaningful use of their EHR systems. This approach holds
      promise as a way to help small primary care practices achieve excellent patient
      outcomes.

PMID- 27864482
TI  - Women's Health.

PMID- 27864483
TI  - Creating a Better State of Health for Women.
AB  - Women's wellness spans from childhood into adolescence, through the childbearing
      period, and into older age. It includes not only wellness issues related to
      cardiovascular disease, cancer, and other chronic conditions but also the
      consequences of intimate partner violence and mental health issues.Throughout the
      life course, women's health should be a priority. Healthier women lead to
      healthier babies, which lead to healthier communities. In addition, when women
      are connected to the health care system, their families are also more likely to
      be connected. This issue of the North Carolina Medical Journal explores the many
      aspects of women's health and its many impacts.

PMID- 27864484
TI  - Down With Teen Pregnancy, Up With Mobility: Teen Pregnancy Prevention Efforts in
      Gaston County, North Carolina.
AB  - Unintended pregnancies are typically associated with poor health outcomes for
      mothers and babies, and they also limit the social mobility of women and their
      families. Gaston County has achieved great success in reducing both teen
      pregnancies and unintended pregnancies among low-income women through the Gaston
      Youth Connected project and the local health department's push to increase
      accessibility to long-acting reversible contraception. Reductions in the racial
      disparities in teen pregnancy rates, higher graduation rates for females, and
      fewer pregnancies among low-income women all indicate a potential for better
      reproductive health to increase the social mobility of Gaston County women. The
      ability to clearly connect health outcomes to long-term social improvements helps
      create sustainable community buy-in and should be a priority in public health
      initiatives.

PMID- 27864485
TI  - A Public-Private Partnership to Reduce Unintended Pregnancy Rates and Improve
      Economic Mobility.

PMID- 27864486
TI  - CenteringPregnancy: Meeting the Quadruple Aim in Prenatal Care.
AB  - CenteringPregnancy is a group prenatal care model that engages pregnant women in
      their care, which results in promising health and system outcomes. This
      commentary will review this innovative care model with a focus on patient
      experience, population health outcomes, cost effectiveness, and provider
      experience.

PMID- 27864487
TI  - Intimate Partner Violence Prevention Programs in North Carolina.
AB  - One in 4 women will experience intimate partner violence in her lifetime. The
      goal of primary intimate partner violence prevention programs is to stop the
      violence before it begins. Secondary prevention programs identify violence that
      is occurring and intervene as soon as possible to prevent the problem from
      progressing. This commentary discusses intimate partner violence, primary and
      secondary prevention, and current prevention programs in North Carolina.

PMID- 27864488
TI  - Domestic Violence and Families: Trauma-Focused Treatment Options.

PMID- 27864489
TI  - Protecting Women Against Human Papillomavirus: Benefits, Barriers, and Evidence
      Based Strategies to Increase Vaccine Uptake.
AB  - Human papillomavirus (HPV) infection significantly impacts women, as it can cause
      cancers and precancers of the cervix, vulva, vagina, oropharynx, and anus.
      However, many of these cancers can be prevented by HPV vaccination. Despite
      evidence of vaccine effectiveness and safety, vaccination rates remain low.
      Evidence-based strategies should be utilized to reduce barriers and increase
      vaccination rates.

PMID- 27864490
TI  - Women and Cardiovascular Disease: What Can Health Care Providers Do to Reduce the
      Risks?
AB  - Cardiovascular disease impacts everybody and places significant burdens on the
      health care system. Educating women on their risks and how to reduce these risks
      will not only make women more aware but will help to improve lives and reduce
      health care costs. This commentary will review heart disease in women and what
      women can do to improve their cardiovascular health.

PMID- 27864491
TI  - North Carolina's Perinatal Health Strategic Plan: Striving to Improve Birth
      Outcomes for All Families.
AB  - While North Carolina has made progress in improving perinatal health, much work
      remains to be done to ensure health for all communities. The state's new
      perinatal health strategic plan provides an innovative approach that highlights
      strategies for addressing biomedical, social, and economic inequalities.

PMID- 27864492
TI  - A Retrospective Look at North Carolina's Efforts to Reduce Infant Mortality.

PMID- 27864493
TI  - Challenges in the Screening and Management of Osteoporosis.
AB  - Osteoporosis imposes a significant burden of morbidity, mortality, and cost on
      patients and the health care system. Compliance with existing screening and
      treatment recommendations is low. There are multiple barriers to treatment
      including complexity of medical management, cost of medications, real and
      perceived side effects of medications, and nonadherence.

PMID- 27864494
TI  - A Review of the Current Cervical Cancer Screening Guidelines.
AB  - For many decades, Pap smear screening has been synonymous with well-woman visits.
      Although Pap smears have greatly decreased the rates of cervical cancer, current
      guidelines support less frequent screening. This commentary reviews the currently
      recommended strategies for cervical cancer screening.

PMID- 27864495
TI  - Urinary Incontinence in Women.
AB  - Urinary incontinence, the involuntary loss of urine, can result from a multitude
      of etiologies and can have a significant negative impact on a woman's physical,
      social, economic, and psychological well-being. This commentary will review the
      current evidence regarding the screening, diagnosis, and treatment options for
      urinary incontinence in women.

PMID- 27864496
TI  - Understanding and Treating Women's Body Image and Eating Disorders.
AB  - This article provides an overview of the etiology of eating disorders, screening
      recommendations, and evidence-based treatment options. These disorders are a
      noteworthy concern among girls and women in the United States, especially given
      the resulting medical comorbidities and high mortality rates.

PMID- 27864497
TI  - The Impact of Infertility on Women's Mental Health.

PMID- 27864498
TI  - Exploring Female Sexuality: Embracing the Whole Narrative.
AB  - Sexuality is inseparable from sexual health and can refer to sex, gender
      identities, orientation, pleasure, intimacy, expression, and reproduction. While
      each element of human sexuality is important, all of these components
      interconnect to make us complete sexual beings. Educators and other human service
      providers thus require professional preparation to ensure they can meet the needs
      of their learners, effectively manage programming, and successfully implement
      strategies that allow individuals to embrace or manage their sexual existence. An
      inclusive approach to sexual health is best to meet the sexual health needs of
      all women, while ensuring their agency and control of their own bodies.

PMID- 27864499
TI  - Project NO REST: Addressing Human Trafficking in North Carolina.
AB  - Project NO REST (North Carolina Organizing and Responding to the Exploitation and
      Sexual Trafficking of Children) is a 5-year effort funded by the US Children's
      Bureau to address the trafficking of individuals age 25 years and younger in
      North Carolina. The project aims to increase awareness of human trafficking
      affecting children and youth, especially those in the child welfare system; to
      reduce the number of these youth who are trafficked; and to improve outcomes for
      those who are trafficked. In the project's first year, nearly 100 stakeholders
      statewide developed a comprehensive plan to address trafficking. Later, 5
      communities were recruited to implement the plan at the local level. Their
      experiences will be used to develop a toolkit for future anti-trafficking
      efforts.

PMID- 27864500
TI  - Issue Brief: Transforming North Carolina's Mental Health and Substance Use
      Systems: A Report from the NCIOM Task Force on Mental Health and Substance Use.

PMID- 27864501
TI  - Editorial for Palliative Medicine.

PMID- 27864505
TI  - Endoscopic Management of Idiopathic Subglottic Stenosis.
AB  - OBJECTIVE: To describe a homogeneous idiopathic subglottic stenosis (ISS)
      population undergoing endoscopic balloon dilation and evaluate factors affecting
      inter-dilation interval (IDI). METHODS: Retrospective review of 37 patients. Co
      morbidity prevalence versus normal population was evaluated using chi-square
      tests. Correlations were evaluated using Pearson product moment tests.
      Independent samples t tests/rank sum tests assessed differences between groups of
      interest. RESULTS: All patients were female aged 45.9 +/- 15.4 years at
      diagnosis. Four required a tracheotomy during management. Most prevalent co
      morbidity was gastroesophageal reflux disease (GERD) (64.9%; P = .036). Body mass
      indices (BMI) at first and most recent dilation were 29.8 and 30.8 ( P = .564).
      Degree of stenosis before first dilation was 53 +/- 14%. Patients underwent 3.8
      +/- 1.8 dilations (range, 1-11). Average IDI was 635 +/- 615 days (range, 49-3130
      days), including 556 +/- 397 days for patients receiving concomitant steroid
      injection and 283 +/- 36 for those who did not ( P = .079). Inter-dilation
      interval was not correlated with BMI ( r = 0.0486; P = .802) or number of co
      morbidities ( r = -0.225, P = .223). CONCLUSIONS: Most patients with ISS can be
      managed endoscopically, and IDI may be increased with steroid injection.
      Gastroesophageal reflux disease is a common co-morbidity. Body mass index did not
      change over time despite potential effects on exercise tolerance; BMI did not
      affect IDI. Methods to determine optimal timing for next intervention are
      warranted.

PMID- 27864504
TI  - Youth Baseball Pitching Stride Length: Normal Values and Correlation With Field
      Testing.
AB  - BACKGROUND: Pitching biomechanical analysis has been recommended as an important
      component of performance, injury prevention, and rehabilitation. Normal values
      for youth pitching stride length have not been established, leading to
      application of normative values found among professional pitchers to youth
      pitchers. HYPOTHESES: The average youth pitching stride length will be
      significantly less than that of college and professional pitchers. There will be
      a positive correlation between stride length, lower extremity power, balance, and
      pitching experience. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE:
      Level 3. METHODS: Ninety-two youth baseball pitchers (aged 9-14 years) met the
      inclusion/exclusion criteria and completed the study. Stride length was recorded
      using a Dartfish video system over 3 maximal effort pitches. Both intra- and
      interrater reliability was calculated for the assessment of stride length. Double
      leg vertical jump, single-leg stance time, leg length, weight, age, and pitching
      experience were also recorded. RESULTS: Mean (SD) stride length was 66.0% (7.1%)
      of height. Stride length was correlated ( P < 0.01) with vertical jump (0.38),
      pitching experience (0.36), and single-leg balance (0.28), with excellent intra-
      and interrater reliability (0.985 or higher). No significant correlations between
      stride length and body weight, leg length, or age existed. CONCLUSIONS: There was
      a significant difference between youth pitching stride length and the current
      published norms for older and more elite throwers. There was a positive
      correlation between stride length and lower extremity power, pitching experience,
      and single-leg balance. CLINICAL RELEVANCE: Two-dimensional analysis of stride
      length allows for the assessment of pitching biomechanics in a practical manner.
      These values can be used for return to pitching parameters after an injury and
      designing injury prevention and performance programs.

PMID- 27864506
TI  - Mitigation of whole-body gamma radiation-induced damages by Clerodendron
      infortunatum in mammalian organisms.
AB  - Several phytoceuticals and extracts of medicinal plants are reported to mitigate
      deleterious effects of ionizing radiation. The potential of hydro-alcoholic
      extract of Clerodendron infortunatum (CIE) for providing protection to mice
      exposed to gamma radiation was investigated. Oral administration of CIE bestowed
      a survival advantage to mice exposed to lethal doses of gamma radiation.
      Radiation-induced depletion of the total blood count and bone marrow cellularity
      were prevented by treatment with CIE. Damage to the cellular DNA (as was evident
      from the comet assay and the micronucleus index) was also found to be decreased
      upon CIE administration. Radiation-induced damages to intestinal crypt cells was
      also reduced by CIE. Studies on gene expression in intestinal cells revealed that
      there was a marked increase in the Bax/Bcl-2 ratio in mice exposed to whole-body
      4 Gy gamma radiation, and that administration of CIE resulted in significant
      lowering of this ratio, suggestive of reduction of radiation-induced apoptosis.
      Also, in the intestinal tissue of irradiated animals, following CIE treatment,
      levels of expression of the DNA repair gene Atm were found to be elevated, and
      there was reduction in the expression of the inflammatory Cox-2 gene. Thus, our
      results suggest a beneficial use of Clerodendron infortunatum for mitigating
      radiation toxicity.

PMID- 27864507
TI  - Multicentre dose audit for clinical trials of radiation therapy in Asia.
AB  - A dose audit of 16 facilities in 11 countries has been performed within the
      framework of the Forum for Nuclear Cooperation in Asia (FNCA) quality assurance
      program. The quality of radiation dosimetry varies because of the large variation
      in radiation therapy among the participating countries. One of the most important
      aspects of international multicentre clinical trials is uniformity of absolute
      dose between centres. The National Institute of Radiological Sciences (NIRS) in
      Japan has conducted a dose audit of participating countries since 2006 by using
      radiophotoluminescent glass dosimeters (RGDs). RGDs have been successfully
      applied to a domestic postal dose audit in Japan. The authors used the same audit
      system to perform a dose audit of the FNCA countries. The average and standard
      deviation of the relative deviation between the measured and intended dose among
      46 beams was 0.4% and 1.5% (k = 1), respectively. This is an excellent level of
      uniformity for the multicountry data. However, of the 46 beams measured, a single
      beam exceeded the permitted tolerance level of +/-5%. We investigated the cause
      for this and solved the problem. This event highlights the importance of external
      audits in radiation therapy.

PMID- 27864508
TI  - Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy
      for glioblastoma.
AB  - The purpose of this study was to evaluate the feasibility and efficacy of
      radiotherapy (RT) using intensity-modulated radiotherapy (IMRT) boosts after
      hyperbaric oxygen (HBO) therapy with chemotherapy in patients with glioblastoma.
      Twenty-four patients with glioblastoma were treated with the combined therapy,
      which was RT using IMRT boosts after HBO with chemotherapy, and were
      retrospectively analyzed. The RT protocol was as follows: first, 3D conformal RT
      [40 Gy/20 fractions (fr)] was delivered to the gross tumor volume (GTV) and the
      surrounding edema, including an additional 1.5-2.0 cm. The IMRT boost doses were
      then continuously delivered to the GTV plus 5 mm (28 Gy/8 fr) and the surrounding
      edema (16 Gy/8 fr). Each IMRT boost session was performed immediately after HBO
      to achieve radiosensitization. The planned RT dose was completed in all patients,
      while HBO therapy was terminated in one patient (4%) due to Grade 2 aural pain.
      The toxicities were mild, no non-hematological toxicity of Grade 3-5 was
      observed. The 2-year overall survival (OS) and progression-free survival rates in
      all patients were 46.5% and 35.4%, respectively. The median OS time was 22.1
      months. In conclusion, the combined therapy of RT using IMRT boosts after HBO
      with chemotherapy was a feasible and promising treatment modality for patients
      with glioblastoma. The results justify further evaluation to clarify the benefits
      of this therapy.

PMID- 27864509
TI  - Loss of beta-adrenergic-stimulated phosphorylation of CaV1.2 channels on Ser1700
      leads to heart failure.
AB  - L-type Ca2+ currents conducted by voltage-gated calcium channel 1.2 (CaV1.2)
      initiate excitation-contraction coupling in the heart, and altered expression of
      CaV1.2 causes heart failure in mice. Here we show unexpectedly that reducing beta
      adrenergic regulation of CaV1.2 channels by mutation of a single PKA site,
      Ser1700, in the proximal C-terminal domain causes reduced contractile function,
      cardiac hypertrophy, and heart failure without changes in expression,
      localization, or function of the CaV1.2 protein in the mutant mice (SA mice).
      These deficits were aggravated with aging. Dual mutation of Ser1700 and a nearby
      casein-kinase II site (Thr1704) caused accelerated hypertrophy, heart failure,
      and death in mice with these mutations (STAA mice). Cardiac hypertrophy was
      increased by voluntary exercise and by persistent beta-adrenergic stimulation.
      PKA expression was increased, and PKA sites Ser2808 in ryanodine receptor type-2,
      Ser16 in phospholamban, and Ser23/24 in troponin-I were hyperphosphorylated in SA
      mice, whereas phosphorylation of substrates for calcium/calmodulin-dependent
      protein kinase II was unchanged. The Ca2+ pool in the sarcoplasmic reticulum was
      increased, the activity of calcineurin was elevated, and calcineurin inhibitors
      improved contractility and ameliorated cardiac hypertrophy. Cardio-specific
      expression of the SA mutation also caused reduced contractility and hypertrophy.
      These results suggest engagement of compensatory mechanisms, which initially may
      enhance the contractility of individual myocytes but eventually contribute to an
      increased sensitivity to cardiovascular stress and to heart failure in vivo. Our
      results demonstrate that normal regulation of CaV1.2 channels by phosphorylation
      of Ser1700 in cardiomyocytes is required for cardiovascular homeostasis and
      normal physiological regulation in vivo.

PMID- 27864510
TI  - Profile of Charles M. Rice, Ralf F. W. Bartenschlager, and Michael J. Sofia, 2016
      Lasker-DeBakey Clinical Medical Research Awardees.

PMID- 27864511
TI  - Root nodule symbiosis in Lotus japonicus drives the establishment of distinctive
      rhizosphere, root, and nodule bacterial communities.
AB  - Lotus japonicus has been used for decades as a model legume to study the
      establishment of binary symbiotic relationships with nitrogen-fixing rhizobia
      that trigger root nodule organogenesis for bacterial accommodation. Using
      community profiling of 16S rRNA gene amplicons, we reveal that in Lotus,
      distinctive nodule- and root-inhabiting communities are established by parallel,
      rather than consecutive, selection of bacteria from the rhizosphere and root
      compartments. Comparative analyses of wild-type (WT) and symbiotic mutants in Nod
      factor receptor5 (nfr5), Nodule inception (nin) and Lotus histidine kinase1
      (lhk1) genes identified a previously unsuspected role of the nodulation pathway
      in the establishment of different bacterial assemblages in the root and
      rhizosphere. We found that the loss of nitrogen-fixing symbiosis dramatically
      alters community structure in the latter two compartments, affecting at least 14
      bacterial orders. The differential plant growth phenotypes seen between WT and
      the symbiotic mutants in nonsupplemented soil were retained under nitrogen
      supplemented conditions that blocked the formation of functional nodules in WT,
      whereas the symbiosis-impaired mutants maintain an altered community structure in
      the nitrogen-supplemented soil. This finding provides strong evidence that the
      root-associated community shift in the symbiotic mutants is a direct consequence
      of the disabled symbiosis pathway rather than an indirect effect resulting from
      abolished symbiotic nitrogen fixation. Our findings imply a role of the legume
      host in selecting a broad taxonomic range of root-associated bacteria that, in
      addition to rhizobia, likely contribute to plant growth and ecological
      performance.

PMID- 27864512
TI  - Epstein-Barr virus super-enhancer eRNAs are essential for MYC oncogene expression
      and lymphoblast proliferation.
AB  - Epstein-Barr virus (EBV) super-enhancers (ESEs) are essential for lymphoblastoid
      cell (LCL) growth and survival. Reanalyses of LCL global run-on sequencing (Gro
      seq) data found abundant enhancer RNAs (eRNAs) being transcribed at ESEs.
      Inactivation of ESE components, EBV nuclear antigen 2 (EBNA2) and bromodomain
      containing protein 4 (BRD4), significantly decreased eRNAs at ESEs -428 and -525
      kb upstream of the MYC oncogene transcription start site (TSS). shRNA knockdown
      of the MYC -428 and -525 ESE eRNA caused LCL growth arrest and reduced cell
      growth. Furthermore, MYC ESE eRNA knockdown also significantly reduced MYC
      expression, ESE H3K27ac signals, and MYC ESEs looping to MYC TSS. These data
      indicate that ESE eRNAs strongly affect cell gene expression and enable LCL
      growth.

PMID- 27864513
TI  - Construction of a male sterility system for hybrid rice breeding and seed
      production using a nuclear male sterility gene.
AB  - The breeding and large-scale adoption of hybrid seeds is an important achievement
      in agriculture. Rice hybrid seed production uses cytoplasmic male sterile lines
      or photoperiod/thermo-sensitive genic male sterile lines (PTGMS) as female
      parent. Cytoplasmic male sterile lines are propagated via cross-pollination by
      corresponding maintainer lines, whereas PTGMS lines are propagated via self
      pollination under environmental conditions restoring male fertility. Despite huge
      successes, both systems have their intrinsic drawbacks. Here, we constructed a
      rice male sterility system using a nuclear gene named Oryza sativa No Pollen 1
      (OsNP1). OsNP1 encodes a putative glucose-methanol-choline oxidoreductase
      regulating tapetum degeneration and pollen exine formation; it is specifically
      expressed in the tapetum and miscrospores. The osnp1 mutant plant displays normal
      vegetative growth but complete male sterility insensitive to environmental
      conditions. OsNP1 was coupled with an alpha-amylase gene to devitalize transgenic
      pollen and the red fluorescence protein (DsRed) gene to mark transgenic seed and
      transformed into the osnp1 mutant. Self-pollination of the transgenic plant
      carrying a single hemizygous transgene produced nontransgenic male sterile and
      transgenic fertile seeds in 1:1 ratio that can be sorted out based on the red
      fluorescence coded by DsRed Cross-pollination of the fertile transgenic plants to
      the nontransgenic male sterile plants propagated the male sterile seeds of high
      purity. The male sterile line was crossed with ~1,200 individual rice germplasms
      available. Approximately 85% of the F1s outperformed their parents in per plant
      yield, and 10% out-yielded the best local cultivars, indicating that the
      technology is promising in hybrid rice breeding and production.

PMID- 27864514
TI  - Proteomics and comparative genomics of Nitrososphaera viennensis reveal the core
      genome and adaptations of archaeal ammonia oxidizers.
AB  - Ammonia-oxidizing archaea (AOA) are among the most abundant microorganisms and
      key players in the global nitrogen and carbon cycles. They share a common energy
      metabolism but represent a heterogeneous group with respect to their
      environmental distribution and adaptions, growth requirements, and genome
      contents. We report here the genome and proteome of Nitrososphaera viennensis
      EN76, the type species of the archaeal class Nitrososphaeria of the phylum
      Thaumarchaeota encompassing all known AOA. N. viennensis is a soil organism with
      a 2.52-Mb genome and 3,123 predicted protein-coding genes. Proteomic analysis
      revealed that nearly 50% of the predicted genes were translated under standard
      laboratory growth conditions. Comparison with genomes of closely related species
      of the predominantly terrestrial Nitrososphaerales as well as the more
      streamlined marine Nitrosopumilales [Candidatus (Ca.) order] and the acidophile
      "Ca. Nitrosotalea devanaterra" revealed a core genome of AOA comprising 860
      genes, which allowed for the reconstruction of central metabolic pathways common
      to all known AOA and expressed in the N. viennensis and "Ca Nitrosopelagicus
      brevis" proteomes. Concomitantly, we were able to identify candidate proteins for
      as yet unidentified crucial steps in central metabolisms. In addition to
      unraveling aspects of core AOA metabolism, we identified specific metabolic
      innovations associated with the Nitrososphaerales mediating growth and survival
      in the soil milieu, including the capacity for biofilm formation, cell surface
      modifications and cell adhesion, and carbohydrate conversions as well as
      detoxification of aromatic compounds and drugs.

PMID- 27864515
TI  - Discovery of cofactor-specific, bactericidal Mycobacterium tuberculosis InhA
      inhibitors using DNA-encoded library technology.
AB  - Millions of individuals are infected with and die from tuberculosis (TB) each
      year, and multidrug-resistant (MDR) strains of TB are increasingly prevalent. As
      such, there is an urgent need to identify novel drugs to treat TB infections.
      Current frontline therapies include the drug isoniazid, which inhibits the
      essential NADH-dependent enoyl-acyl-carrier protein (ACP) reductase, InhA. To
      inhibit InhA, isoniazid must be activated by the catalase-peroxidase KatG.
      Isoniazid resistance is linked primarily to mutations in the katG gene. Discovery
      of InhA inhibitors that do not require KatG activation is crucial to combat MDR
      TB. Multiple discovery efforts have been made against InhA in recent years. Until
      recently, despite achieving high potency against the enzyme, these efforts have
      been thwarted by lack of cellular activity. We describe here the use of DNA
      encoded X-Chem (DEX) screening, combined with selection of appropriate physical
      properties, to identify multiple classes of InhA inhibitors with cell-based
      activity. The utilization of DEX screening allowed the interrogation of very
      large compound libraries (1011 unique small molecules) against multiple forms of
      the InhA enzyme in a multiplexed format. Comparison of the enriched library
      members across various screening conditions allowed the identification of
      cofactor-specific inhibitors of InhA that do not require activation by KatG, many
      of which had bactericidal activity in cell-based assays.

PMID- 27864518
TI  - Housing improvement: a novel paradigm for urban vector-borne disease control?

PMID- 27864519
TI  - Faith and Marital Violence in Sub-Saharan Africa: Exploring the Links Between
      Religious Affiliation and Intimate Partner Violence Among Women in Ghana.
AB  - Research shows that intimate partner violence is quite widespread throughout the
      world. In the case of sub-Saharan Africa (SSA), studies have concluded that
      cultural and economic factors help to sustain the spread and maintenance of
      intimate partner violence in the region. Although the cultural interpretations
      predominate in current research, few have examined the links between religion, an
      important cultural variable, and intimate partner violence in SSA. Given the
      growth and importance of religion in African cultures, we used data from the 2008
      Ghana Demographic Health Survey ( n = 1,831) and ordinary least squares
      regression method to investigate the links between religious affiliation and
      intimate partner violence. Findings from our study point to some variations in
      intimate partner violence by affiliation. This is especially true with regard to
      women's experience with sexual violence and emotional violence. Besides religion,
      we also found ideologies that support wife abuse, the nature of decision-making
      process at the household level, and husband's use of alcohol to be important
      determinants of intimate partner violence in Ghana. We examined the implications
      of these findings.

PMID- 27864516
TI  - On the (un)predictability of a large intragenic fitness landscape.
AB  - The study of fitness landscapes, which aims at mapping genotypes to fitness, is
      receiving ever-increasing attention. Novel experimental approaches combined with
      next-generation sequencing (NGS) methods enable accurate and extensive studies of
      the fitness effects of mutations, allowing us to test theoretical predictions and
      improve our understanding of the shape of the true underlying fitness landscape
      and its implications for the predictability and repeatability of evolution. Here,
      we present a uniquely large multiallelic fitness landscape comprising 640
      engineered mutants that represent all possible combinations of 13 amino acid
      changing mutations at 6 sites in the heat-shock protein Hsp90 in Saccharomyces
      cerevisiae under elevated salinity. Despite a prevalent pattern of negative
      epistasis in the landscape, we find that the global fitness peak is reached via
      four positively epistatic mutations. Combining traditional and extending recently
      proposed theoretical and statistical approaches, we quantify features of the
      global multiallelic fitness landscape. Using subsets of the data, we demonstrate
      that extrapolation beyond a known part of the landscape is difficult owing to
      both local ruggedness and amino acid-specific epistatic hotspots and that
      inference is additionally confounded by the nonrandom choice of mutations for
      experimental fitness landscapes.

PMID- 27864517
TI  - An extensive burden of giardiasis associated with intestinal schistosomiasis and
      anaemia in school children on the shoreline of Lake Albert, Uganda.
AB  - BACKGROUND: Water-borne parasitic diseases associated with poverty still blight
      the lives of African school children. In Uganda, intestinal schistosomiasis is
      still common along the shoreline of Lake Albert, despite ongoing control, and co
      infection with giardiasis and malaria is poorly described. To shed light on
      putative interactions between diseases, a prospective cross-sectional
      parasitological survey was undertaken in five primary schools. METHODS: Stool
      samples from 254 school children, aged 5-10 years, were examined by microscopy
      and rapid diagnostic tests (RDTs), with additional real-time PCR assays for
      detection of Giardia DNA. A finger-prick blood sample was also taken from each
      child and tested for malaria, and haemoblobin levels measured. Assocations
      between diseases and anaemia were assessed. RESULTS: Intestinal schistosomiasis
      (46.5%), giardiasis (41.6%) and malaria (56.2%) were common, and a quarter of
      children were anaemic (<115 g/L). Up to 87.0% of children were excreting Giardia
      DNA and the prevalence of heavy infection by real-time PCR (Ct<=19) was 19.5%,
      being positively associated with light, moderate and heavy egg-patent
      schistosomiasis, as well as with anaemia. CONCLUSIONS: In this setting, an
      extensive burden of giardiasis was revealed with heavy intensity infections
      associated with egg-patent intestinal schistosomiasis and anaemia. To improve
      child health, greater attention on giardiasis is needed along with exploring
      joined-up actions across diseases that promote better water hygiene and
      sanitation measures.

PMID- 27864520
TI  - Ibrutinib monotherapy in relapsed/refractory CNS lymphoma: A retrospective case
      series.

PMID- 27864521
TI  - Enlargement of deep medullary veins during the early clinical course of Sturge
      Weber syndrome.

PMID- 27864522
TI  - Comorbidity between central disorders of hypersomnolence and immune-based
      disorders.
AB  - OBJECTIVE: To assess and compare the frequencies of personal and family history
      of autoimmune diseases (AID), autoinflammatory disorders (ID), and allergies in a
      population of patients, adults and children, with narcolepsy type 1 (NT1),
      narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), 3 central hypersomnia
      disorders, and healthy controls. METHODS: Personal and family history of AID, ID,
      and allergies were assessed by questionnaire and medical interview in a large
      cohort of 450 consecutive adult patients (206 NT1, 106 NT2, 138 IH) and 95
      pediatric patients (80 NT1) diagnosed according to the third International
      Classification of Sleep Disorders criteria in national reference centers for
      narcolepsy in France and 751 controls (700 adults, 51 children) from the general
      population. RESULTS: Ten adults with NT1 (4.9%) had a comorbid AID vs 3.4% of
      adult controls, without between-group differences in adjusted models. AID
      frequency did not differ between children with NT1 and controls. Conversely,
      compared with controls, AID frequency was higher in adults with NT2 (p = 0.002),
      whereas ID (p = 0.0002) and allergy (p = 0.003) frequencies were higher in adults
      with IH. A positive family history of AID was found in the NT1 group and of ID in
      the IH group. CONCLUSIONS: NT1 is not associated with increased risk of comorbid
      immune disorders, in favor of a potentially unique pathophysiology. Conversely,
      compared with controls, the frequency of autoimmune diseases was higher in adults
      with NT2, whereas allergies and autoinflammatory disorders were more common in
      adults with IH, suggesting an immune dysregulation mechanism in these conditions.

PMID- 27864523
TI  - Carotid artery web and ischemic stroke: A case-control study.
AB  - OBJECTIVE: To determine whether there is an association between carotid artery
      web and ischemic stroke. METHODS: This was a single-center, age- and sex-matched,
      case-control study. Cases were consecutive patients with anterior circulation
      ischemic stroke of undetermined etiology (Trial of Org 10172 in Acute Stroke
      Treatment [TOAST] classification). Controls were consecutive patients with
      cerebral aneurysms, arteriovenous malformations, or primary intracerebral
      hemorrhages. Additional inclusion criteria were age <60 years and CT angiography
      of the neck. Two neuroradiologists diagnosed webs according to previously
      published criteria. One neuroradiologist also assessed for nonstenotic
      atherosclerotic plaque (carotid wall thickness >=3 mm or intramural
      calcification). We used conditional logistic regression to estimate the odds
      ratio between carotid web and ischemic stroke and its 95% confidence interval.
      RESULTS: Fifty-three of 62 cases (85%) were matched by age (within 1 year) and by
      sex to 102 controls. There was a carotid web in 4 of 53 cases (9.4%) vs 1 of 102
      controls (1.0%, odds ratio = 8.0, 95% confidence interval = 1.2-67, p = 0.032).
      There was no significant difference in the prevalence of nonstenotic carotid
      atherosclerotic plaque between the case and control groups. There was agreement
      on diagnosis of web for 163 of 164 patients (99%) and 7 of 8 webs (88%), and the
      Cohen kappa for interobserver agreement was 0.93. CONCLUSIONS: There is an
      association between carotid artery web and ischemic stroke in patients who lack
      an alternative cause of stroke. Carotid web may be an underappreciated risk
      factor for stroke.

PMID- 27864525
TI  - AEDs after ICH: Preventing the prophylaxis.

PMID- 27864524
TI  - Evolving use of seizure medications after intracerebral hemorrhage: A multicenter
      study.
AB  - OBJECTIVE: Prophylactic medications can be a source of preventable harm,
      potentially affecting large numbers of patients. Few data exist about how
      clinicians change prescribing practices in response to new data and revisions to
      guidelines about preventable harm from a prophylactic medication. We sought to
      determine the changes in prescribing practice of seizure medications for patients
      with intracerebral hemorrhage (ICH) across a metropolitan area before and after
      new outcomes data and revised prescribing guidelines were published. METHODS: We
      conducted an observational study using electronic medical record data from 4
      academic medical centers in a large US metropolitan area. RESULTS: A total of
      3,422 patients with ICH, diagnosed between 2007 and 2012, were included. In 2009,
      after a publication found an association of phenytoin with higher odds of
      dependence or death, the use of phenytoin declined from 9.6% in 2009 to 2.2% in
      2012 (p < 0.00001). Conversely, the use of levetiracetam more than doubled, from
      15.1% in 2007 to 35% in 2012 (p < 0.00001). Use of levetiracetam varied among the
      4 institutions from 6.7% to 29.8% (p < 0.00001). CONCLUSIONS: New data that led
      to revised prescribing guidelines for prophylactic seizure medications for
      patients with ICH were temporally associated with a significant decrease in use
      of the medication, potentially reducing adverse outcomes. However, a
      corresponding increase in the use of an alternative medication, levetiracetam,
      occurred despite limited knowledge about its potential effects on outcomes.
      Future guideline changes should anticipate and address alternatives.

PMID- 27864526
TI  - RAB39a binds caspase-1 and is required for caspase-1-dependent interleukin-1beta
      secretion.

PMID- 27864527
TI  - IL-1-induced post-transcriptional mechanisms target overlapping translational
      silencing and destabilizing elements in IkappaBzeta mRNA.

PMID- 27864528
TI  - IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88
      adaptor-like (Mal).

PMID- 27864529
TI  - Subversion of Schwann cell glucose metabolism by Mycobacterium leprae.

PMID- 27864530
TI  - Why Information Matters: Examining the Consequences of Suggesting That Pedophilia
      Is Immutable.
AB  - In this study, the impact of suggesting that pedophilia is immutable on a man's
      specific self-efficacy for modifying his sexual interest in children was examined
      in 94 men with a sexual interest in children. The participants were selected from
      differing contexts and included non-forensic patients, forensic patients, and
      participants from the Internet. Randomly distributed to two conditions, the
      mutable condition group received the information that experts consider pedophilia
      to be modifiable, whereas the immutable condition group received the information
      that experts consider pedophilia to be stable. Afterward, the participants'
      levels of specific self-efficacy for modifying their sexual interest in children
      were assessed. Non-forensic participants in the mutable condition reported higher
      levels of specific self-efficacy than those in the immutable condition. No
      differences in specific self-efficacy were revealed for the forensic and Internet
      participants when comparing the mutable and immutable conditions. It would appear
      appropriate to avoid generalized and absolute statements about the (im)mutability
      of sexual interest in children, as scientific research on this topic remains
      insufficient. Furthermore, given the present results, such statements might have
      serious consequences for an individual's belief in being able to change his
      sexual interest in children.

PMID- 27864531
TI  - Familial Depressive Symptoms and Delinquency: Separate Self-Reports From Mothers
      and Their Offspring.
AB  - Research has documented that both unipolar and bipolar depression are positively
      correlated with involvement in delinquency and crime. The present study sought to
      broaden the understanding of these relationships by looking for links between
      offending and family histories of depressive symptoms in relationship to
      offspring delinquency. More than 6,000 college students and their mothers
      provided self-reported information regarding feelings of depression. Students
      provided self-reports of involvement in various categories of offending and drug
      use from ages 10 through 18. Numerous significant positive correlations were
      found between general feelings of depression and of manic depression and
      involvement in delinquency. The depression-delinquency relationships were
      strongest when considering offspring themselves, although maternal depression
      symptoms were also associated with various forms of offspring delinquency and
      drug use. To help assess the causal chains that might be involved, multiple
      regression and mediation analysis revealed that parental depression enhanced the
      probability of offspring feeling depressed and may have thereby contributed to
      offspring being delinquent, particularly in the case of manic depression. This
      study reconfirmed the well-established relationship between depression and
      involvement in delinquency and drug use, and suggests that it extends back to
      parental forms of depression, especially by the mother.

PMID- 27864532
TI  - The Impact of Types and Extent of Trauma on Depressive Affect Among Male Juvenile
      Sexual Offenders.
AB  - High levels of depression have been found among incarcerated youth, which
      suggests that mental health problems are associated with delinquent behavior and
      are part of a constellation of risk factors that contribute to youth entering the
      juvenile justice system. In this project, we investigated trauma and mental
      health issues among male youth in residential treatment, and addressed the
      following questions: (a) Does childhood trauma predict current depression for
      male juvenile sexual offenders? (b) If so, do different types of traumas predict
      depressive affect better than others? and, (c) Does extent of trauma exposure
      predict depression? Data on incarcerated male juvenile sexual offenders were
      analyzed ( n = 379). Multiple regressions of various types of traumas and
      cumulative trauma and depression were conducted. Emotional abuse was the
      strongest predictor of depressive affect for this sample, and multiple exposures
      to trauma were the second strongest predictor.

PMID- 27864533
TI  - Calculating Probability in Sex Offender Risk Assessment.
AB  - Risk is the probability of an adverse event or outcome. In a previous article, I
      compared the Bayesian and Frequentist models of defining probability. This
      article compares the Bayesian and regression models of quantifying probability.
      Both approaches are widely used in the biomedical and behavioral sciences even
      though they yield different results. No consensus has emerged as to which is more
      appropriate. The choice between them remains controversial. This article
      concludes that the Bayesian model provides a viable alternative to logistic
      regression and may be more useful in quantifying the absolute recidivism risk of
      individual sex offenders. It shows how evaluators can easily calculate Bayesian
      probabilities and their associated credible intervals from an actuarial data set.
      Last, the article proposes a forensic practice guideline that evaluators do not
      conclude that an offender meets an absolute risk threshold unless the subject's
      risk exceeds the threshold by a credible margin of error.

PMID- 27864534
TI  - Microbiome and nutrition in autism spectrum disorder: current knowledge and
      research needs.
AB  - Autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder
      in the United States. Besides genetic risks, environmental factors have been
      suggested to contribute to the increase in ASD diagnosis over the past decade.
      Several studies have reported abnormalities in microbiota composition and
      differences in microbial metabolites in children with ASD. Gastrointestinal
      discomfort is commonly reported in children with ASD. Additionally, food
      selectivity and picky eating patterns are commonly reported. A number of
      mechanisms underlying the interaction between nutrition, the gut microbiota, and
      ASD symptoms via the microbiota-gut-brain axis have been proposed, including
      immune, hormonal, or neuronal pathways. Here, the current evidence base regarding
      the gut environment and nutritional status of children with ASD is reviewed.
      Potential underlying mechanisms of the microbiota-gut-brain axis in ASD and the
      interplay between nutrition, microbiota, and ASD symptoms are also reviewed.
      Future studies investigating the microbiota in the context of dietary intake are
      needed to increase understanding of the interplay between diet and the gut
      microbiota in ASD and to identify potential dietary, probiotic, or prebiotic
      intervention strategies.

PMID- 27864537
TI  - Effects of probiotic supplementation in patients with type 2 diabetes: systematic
      review and meta-analysis.
AB  - CONTEXT: The rising prevalence of type 2 diabetes requires increased efforts to
      find effective therapeutic agents for this complex condition. Following the
      recent observation that the gut microbiota is altered in diabetic patients,
      researchers investigated the effect of probiotics in patients with diabetes.
      OBJECTIVE: The aim of this systematic review was to assess the effects of
      probiotic consumption on glycemic control in diabetic patients. DATA SOURCES:
      PubMed, Scopus, Web of Science (formerly ISI Web of Knowledge), Cochrane Central
      Register of Controlled Trials, ClinicalTrials.gov, and ProQuest Dissertations and
      Theses databases were searched up to November 2015. STUDY SELECTION: Clinical
      trials in diabetic patients in whom probiotics were administered as an
      intervention were included. DATA EXTRACTION: Primary outcomes were fasting blood
      glucose, insulin concentration, insulin resistance, and hemoglobin A1c. Secondary
      outcomes were adverse events. DATA SYNTHESIS: Of the 2736 reports that were
      screened, 13 clinical trials met the inclusion criteria. Pooling data from
      eligible clinical trials revealed that probiotic supplementation significantly (P
      < 0.05) decreased fasting blood glucose and hemoglobin A1c in diabetic patients,
      although the participants' characteristics (eg, body mass index) and the number
      and type of probiotic microorganisms affected the clinical response. CONCLUSIONS:
      Administration of probiotics appears to have a beneficial role in the management
      of type 2 diabetes; however, more clinical studies with adequate sample sizes and
      sound methodology are required to inform the development of evidence-based
      treatment guidelines.

PMID- 27864538
TI  - Erratum for "Role of maternal vitamins in programming health and chronic
      disease." Nutrition Reviews 2016; 74: 166-180.

PMID- 27864536
TI  - Influence of dietary protein and its amino acid composition on postoperative
      outcomes after gastric bypass surgery: a systematic review.
AB  - CONTEXT: Bariatric surgery is an effective method to reduce morbid obesity.
      Nutritional counseling is essential to achieve maximal treatment success and to
      avoid long-term complications. Increased dietary protein intake may improve
      various postoperative results. OBJECTIVE: The aim of this systematic review is to
      examine the relationship between intake of dietary protein or supplementation
      with amino acids and postoperative outcomes after gastric bypass surgery. DATA
      SOURCES: A systematic literature search was conducted in 4 electronic databases:
      Cochrane, Embase, PubMed, and Scopus. STUDY SELECTION: The initial search
      retrieved 7333 hits, which included 2390 duplicates. DATA EXTRACTION: Tweny-three
      studies with varying study designs, interventions, and outcomes were included.
      RESULTS: Studies did not provide convincing evidence of a beneficial effect on
      any postoperative outcome. CONCLUSIONS: The study of the influence of protein and
      its amino acid composition represents an important developing domain of knowledge
      and warrants further attention considering the popularity of bariatric surgery.
      Future studies should include a clear description of the quantity and composition
      of proteins and amino acids in the diet or supplement.

PMID- 27864535
TI  - Effect of diet on mortality and cancer recurrence among cancer survivors: a
      systematic review and meta-analysis of cohort studies.
AB  - CONTEXT: Evidence of an association between dietary patterns and individual foods
      and the risk of overall mortality among cancer survivors has not been reviewed
      systematically. OBJECTIVE: The aim of this meta-analysis of cohort studies was to
      investigate the association between food intake and dietary patterns and overall
      mortality among cancer survivors. DATA SOURCES: The PubMed and Embase databases
      were searched. STUDY SELECTION: A total of 117 studies enrolling 209 597 cancer
      survivors were included. DATA EXTRACTION: The following data were extracted:
      study location, types of outcome, population characteristics, dietary assessment
      method, risk estimates, and adjustment factors. RESULTS: Higher intakes of
      vegetables and fish were inversely associated with overall mortality, and higher
      alcohol consumption was positively associated with overall mortality (RR, 1.08;
      95%CI, 1.02-1.16). Adherence to the highest category of diet quality was
      inversely associated with overall mortality (RR, 0.78; 95%CI, 0.72-0.85;
      postdiagnosis RR, 0.79; 95%CI, 0.71-0.89), as was adherence to the highest
      category of a prudent/healthy dietary pattern (RR, 0.81; 95%CI, 0.67-0.98;
      postdiagnosis RR, 0.77; 95%CI, 0.60-0.99). The Western dietary pattern was
      associated with increased risk of overall mortality (RR, 1.46; 95%CI, 1.27-1.68;
      postdiagnosis RR, 1.51; 95%CI, 1.24-1.85). CONCLUSION: Adherence to a high
      quality diet and a prudent/healthy dietary pattern is inversely associated with
      overall mortality among cancer survivors, whereas a Western dietary pattern is
      positively associated with overall mortality in this population.

PMID- 27864541
TI  - Overexpression of soybean miR172c confers tolerance to water deficit and salt
      stress, but increases ABA sensitivity in transgenic Arabidopsis thaliana.

PMID- 27864539
TI  - Bundle-sheath leakiness and intrinsic water use efficiency of a perennial C4
      grass are increased at high vapour pressure deficit during growth.
AB  - Bundle-sheath leakiness (phi) is a key parameter of the CO2-concentrating
      mechanism of C4 photosynthesis and is related to leaf-level intrinsic water use
      efficiency (WUEi). This work studied short-term dynamic responses of phi to
      alterations of atmospheric CO2 concentration in Cleistogenes squarrosa, a
      perennial grass, grown at high (1.6 kPa) or low (0.6 kPa) vapour pressure deficit
      (VPD) combined with high or low N supply in controlled environment experiments.
      phi was determined by concurrent measurements of photosynthetic gas exchange and
      on-line carbon isotope discrimination, using a new protocol. Growth at high VPD
      led to an increase of phi by 0.13 and a concurrent increase of WUEi by 14%, with
      similar effects at both N levels. phi responded dynamically to intercellular CO2
      concentration (C i), increasing with C i Across treatments, phi was negatively
      correlated to the ratio of CO2 saturated assimilation rate to carboxylation
      efficiency (a proxy of the relative activities of Rubisco and phosphoenolpyruvate
      carboxylase) indicating that the long-term environmental effect on phi was
      related to the balance between C3 and C4 cycles. Our study revealed considerable
      dynamic and long-term variation in phi of C. squarrosa, suggesting that phi
      should be determined when carbon isotope discrimination is used to assess WUEi
      Also, the data indicate a trade-off between WUEi and energetic efficiency in C.
      squarrosa.

PMID- 27864544
TI  - From the Cover: Investigative Nonclinical Cardiovascular Safety and Toxicology
      Studies with BMS-986094, an NS5b RNA-Dependent RNA Polymerase Inhibitor.
AB  - BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment
      of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials
      because of unexpected cardiac and renal adverse events. Investigative nonclinical
      studies were conducted to extend the understanding of these findings using more
      comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and
      150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d)
      for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for
      toxicology). Endpoints included toxicokinetics; echocardiography, telemetric
      hemodynamics and electrocardiography, and tissue injury biomarkers (monkey); and
      light and ultrastructural pathology of heart, kidney, and skeletal muscle
      (mouse/monkey). Dose-related and time-dependent findings included: severe
      toxicity in mice at 150 mg/kg/d and monkeys at 30 mg/kg/d; decreased left
      ventricular (LV) ejection fraction, fractional shortening, stroke volume, and
      dP/dt; LV dilatation, increased QTc interval, and T-wave flattening/inversion
      (monkeys at >= 15 mg/kg/d); cardiomyocyte degeneration (mice at 150 mg/kg/d and
      monkeys at >= 15 mg/kg/d) with myofilament lysis/myofbril disassembly; time
      dependent proteinuria and increased urine beta-2 microglobulin, calbindin,
      clusterin; kidney pallor macroscopically; and tubular dilatation (monkeys);
      tubular regeneration (mice 150 mg/kg/d); and acute proximal tubule degeneration
      ultrastructurally (mice/monkeys); and skeletal muscle degeneration with increased
      urine myoglobin and serum sTnI. These studies identified changes not described
      previously in studies of BMS-986094 including premonitory cardiovascular
      functional changes as well as additional biomarkers for muscle and renal
      toxicities. Although the mechanism of potential toxicities observed in BMS-986094
      studies was not established, there was no evidence for direct mitochondrial
      toxicity.

PMID- 27864546
TI  - Comment on "DNA Sensing via TLR-9 Constitutes a Major Innate Immunity Pathway
      Activated during Erythema Nodosum Leprosum".

PMID- 27864547
TI  - Response to Comment on "DNA Sensing via TLR-9 Constitutes a Major Innate Immunity
      Pathway Activated during Erythema Nodosum Leprosum".

PMID- 27864543
TI  - Long Non-Coding RNAs: A Novel Paradigm for Toxicology.
AB  - Long non-coding RNAs (lncRNAs) are over 200 nucleotides in length and are
      transcribed from the mammalian genome in a tissue-specific and developmentally
      regulated pattern. There is growing recognition that lncRNAs are novel biomarkers
      and/or key regulators of toxicological responses in humans and animal models.
      Lacking protein-coding capacity, the numerous types of lncRNAs possess a myriad
      of transcriptional regulatory functions that include cis and trans gene
      expression, transcription factor activity, chromatin remodeling, imprinting, and
      enhancer up-regulation. LncRNAs also influence mRNA processing, post
      transcriptional regulation, and protein trafficking. Dysregulation of lncRNAs has
      been implicated in various human health outcomes such as various cancers,
      Alzheimer's disease, cardiovascular disease, autoimmune diseases, as well as
      intermediary metabolism such as glucose, lipid, and bile acid homeostasis.
      Interestingly, emerging evidence in the literature over the past five years has
      shown that lncRNA regulation is impacted by exposures to various chemicals such
      as polycyclic aromatic hydrocarbons, benzene, cadmium, chlorpyrifos-methyl,
      bisphenol A, phthalates, phenols, and bile acids. Recent technological
      advancements, including next-generation sequencing technologies and novel
      computational algorithms, have enabled the profiling and functional
      characterizations of lncRNAs on a genomic scale. In this review, we summarize the
      biogenesis and general biological functions of lncRNAs, highlight the important
      roles of lncRNAs in human diseases and especially during the toxicological
      responses to various xenobiotics, evaluate current methods for identifying
      aberrant lncRNA expression and molecular target interactions, and discuss the
      potential to implement these tools to address fundamental questions in
      toxicology.

PMID- 27864549
TI  - The Old One-Two: Solving the Mystery of Cognate Help.

PMID- 27864550
TI  - Pillars Article: A 39-kDa Protein on Activated Helper T Cells Binds CD40 and
      Transduces the Signal for Cognate Activation of B Cells. Proc. Natl. Acad. Sci.
      1992. 89: 6550-6554.

PMID- 27864553
TI  - Correction: Transcription Factors Directing Th2 Differentiation: Gata-3 Plays a
      Dominant Role.

PMID- 27864548
TI  - From IgE to Omalizumab.
AB  - IgE is the least abundant Ig isotype, yet it plays a critical role in allergic
      reactions and host protection from helminth infection. Although IgE was
      discovered 50 years ago, the ultimate evidence for its role in human allergic
      diseases was obtained by the efficacy of anti-IgE therapy in many clinical trials
      on asthma and other allergic diseases. Beginning from the discovery of IgE 50 y
      ago, followed by studies of IgE receptors and activation mechanisms, this review
      provides a historic perspective of allergy research that has led to the
      development of anti-IgE therapy and other strategies targeting IgE and its
      receptors. Current IgE studies toward future precision medicine are also
      reviewed.

PMID- 27864551
TI  - Immunological Outcomes of Antibody Binding to Glycans Shared between
      Microorganisms and Mammals.
AB  - Glycans constitute basic cellular components of living organisms across
      biological kingdoms, and glycan-binding Abs participate in many cellular
      interactions during immune defense against pathogenic organisms. Glycan epitopes
      are expressed as carbohydrate-only entities or as oligomers or polymers on
      proteins and lipids. Such epitopes on glycoproteins may be formed by
      posttranslational modifications or neoepitopes resulting from metabolic-catabolic
      processes and can be altered during inflammation. Pathogenic organisms can
      display host-like glycans to evade the host immune response. However, Abs to
      glycans, shared between microorganisms and the host, exist naturally. These Abs
      are able to not only protect against infectious disease, but also are involved in
      host housekeeping functions and can suppress allergic disease. Despite the
      reactivity of these Abs to glycans shared between microorganisms and host,
      diverse tolerance-inducing mechanisms permit the B cell precursors of these Ab
      secreting cells to exist within the normal B cell repertoire.

PMID- 27864555
TI  - Working Memory Capacity Predicts Selection and Identification Errors in Visual
      Search.
AB  - As public safety relies on the ability of professionals, such as radiologists and
      baggage screeners, to detect rare targets, it could be useful to identify
      predictors of visual search performance. Schwark, Sandry, and Dolgov found that
      working memory capacity (WMC) predicts hit rate and reaction time in low
      prevalence searches. This link was attributed to higher WMC individuals
      exhibiting a higher quitting threshold and increasing the probability of finding
      the target before terminating search in low prevalence search. These conclusions
      were limited based on the methods; without eye tracking, the researchers could
      not differentiate between an increase in accuracy due to fewer identification
      errors (failing to identify a fixated target), selection errors (failing to
      fixate a target), or a combination of both. Here, we measure WMC and correlate it
      with reaction time and accuracy in a visual search task. We replicate the finding
      that WMC predicts reaction time and hit rate. However, our analysis shows that it
      does so through both a reduction in selection and identification errors. The
      correlation between WMC and selection errors is attributable to increased
      quitting thresholds in those with high WMC. The correlation between WMC and
      identification errors is less clear, though potentially attributable to increased
      item inspection times in those with higher WMC. In addition, unlike Schwark and
      coworkers, we find that these WMC effects are fairly consistent across prevalence
      rates rather than being specific to low-prevalence searches.

PMID- 27864554
TI  - Nostril Advantage in Trigeminal/Olfactory Perception and Its Relation to
      Handedness.
AB  - Introduction Few studies investigated nostril-advantage in chemosensory
      perception, particularly, in relation to handedness. The aim of the present
      article was therefore to assess whether trigeminal/olfactory perception is
      altered by handedness. Methods We tested 50 (all right-handed) and 43 (22 left
      handed) participants in Studies 1 and 2, respectively. We used binary mixtures of
      cinnamaldehyde and eucalyptol, in different proportions presented as physical
      mixtures (the same exact mixture presented birhinally to each nostril) or as a
      dichorhinic mixtures (different mixtures presented to each nostril). Presenting
      dichorhinic mixtures allowed us to assess nostril dominance based on
      participants' report on whether the mixture smelled more like cinnamon or
      eucalyptus. Participants also evaluated whether the stimuli were "painful,"
      "warm," "cold," and "intense" on visual scales. Results In Study 1, we find that
      in right handers, stimuli presented to the right nostril dominated over those
      presented to the left nostril. These stimuli were also rated as more "painful"
      and "intense." In Study 2, we could not corroborate the findings in the right
      handed individuals, and we found limited support for a nostril advantage left
      handed individuals. Conclusion Although our data points toward a certain nostril
      advantage in chemosensory perception, the finding is not systematic, we discuss
      possible underlying factors.

PMID- 27864556
TI  - The Independent Perceptual Calibration of Action-Neutral and -Referential
      Environmental Properties.
AB  - Two experiments were conducted to explore how the calibration of perception of
      environmental properties taken with reference to an animal and their action
      capabilities (e.g., affordances) and those that are independent of action
      capabilities (e.g., metric properties) relate. In both experiments, participants
      provided reports of the maximum height they could reach above their head with a
      number of different stick(s) (reach-with-stick height) and the length of those
      stick(s), a property that is a constituent of reach-with-stick height. In
      Experiment 1 reach-with-stick height reports improved over trials whereas stick
      length reports remained constant. In Experiment 2, feedback about maximum reach
      with-stick height improved perception of this affordance, but such improvements
      did not transfer to perception of stick length in a pretest/practice
      task/posttest design. The results suggest that the perceptual calibration with
      practice perceiving or feedback about actual dimensions of action-referential and
      action-neutral properties do not necessarily depend on one another.

PMID- 27864552
TI  - Immune-Mediated Protection and Pathogenesis of Chikungunya Virus.
AB  - Chikungunya virus (CHIKV) is a re-emerging alphavirus that causes debilitating
      acute and chronic arthritis. Infection by CHIKV induces a robust immune response
      that is characterized by production of type I IFNs, recruitment of innate and
      adaptive immune cells, and development of neutralizing Abs. Despite this
      response, chronic arthritis can develop in some individuals, which may be due to
      a failure to eliminate viral RNA and Ag and/or persistent immune responses that
      cause chronic joint inflammation. In this review, based primarily on advances
      from recent studies in mice, we discuss the innate and adaptive immune factors
      that control CHIKV dissemination and clearance or contribute to pathogenesis.

PMID- 27864559
TI  - Effect of Calcaneus Fracture Gap Without Step-Off on Stress Distribution Across
      the Subtalar Joint.
AB  - BACKGROUND: Subtalar arthritis is a common consequence following calcaneal
      fracture, and its development is related to the severity of the fracture.
      Previous calcaneal fracture models have demonstrated altered contact
      characteristics when a step-off is created in the posterior facet articular
      surface. Changes in posterior facet contact characteristics have not been
      previously characterized for calcaneal fracture gap without step-off. METHODS:
      The contact characteristics (peak pressure, area of contact, and centroid of
      pressure) of the posterior facet of the subtalar joint were determined in 6
      cadaveric specimens. After creating a calcaneal fracture to simulate a Sanders
      type II fracture, the contact characteristics were determined with the posterior
      facet anatomically reduced followed by an incremental increase in fracture gap
      displacement of 2, 3, and 5 mm without a step-off of the articular surface.
      RESULTS: Peak pressure on the medial fragment was significantly less with a 5-mm
      gap compared to a 2- or 3-mm gap, or reduced. On the lateral fragment, the peak
      pressure was significantly increased with a 5-mm gap compared to a 2- or 3-mm
      gap. Contact area significantly changed with increased gap. CONCLUSION: In this
      study, there were no significant differences in contact characteristics between a
      <3-mm gap and an anatomically reduced fracture, conceding the study limitations
      including limiting axial loading to 50% of donor body weight. CLINICAL RELEVANCE:
      A small amount of articular incongruity without a step-off can be tolerated by
      the subtalar joint, in contrast to articular incongruity with a step-off present.

PMID- 27864558
TI  - Prospective study of the innate cellular immune response in low vaccine responder
      children.
AB  - We recently reported our findings from a longitudinal, prospective study where we
      identified 10% infants who were low vaccine responders (LVR) at age 9-12 mo
      following routine primary series vaccine schedule. We found multiple cellular
      deficiencies in LVR children, including low number of memory B cells, reduced
      polyclonal stimulation of naive/memory T cell response and suboptimal APC
      response. These children outgrew their poor vaccine response by the time they
      received booster doses of vaccine. Studies in human infant innate immunity are
      rare because of the unique challenges in specimen collection. As innate immunity
      instructs adaptive immunity, we hypothesized that the primary immune defect lies
      with innate immunity and in this study we sought to determine the ontogeny of
      innate immune response in LVR children between 6 and 36 mo of age. Interestingly,
      suboptimal APC response observed in LVR children at 6-9 mo of age characterized
      by significantly ( P < 0.05) low basal MHC II expression, low R848 induced IRF7
      fold change, as well as low IFN-alpha, IL-12p70 and IL-1beta levels, came to
      parity with normal vaccine responders by 12-15 mo of age, suggesting that the
      observed immune deficiency in LVR children may be the result of delayed
      maturation of immune system.

PMID- 27864560
TI  - What is pathological May-Thurner syndrome?

PMID- 27864561
TI  - Incidence of deep vein thrombosis in patients undergoing breast reconstruction
      with autologous tissue transfer.
AB  - Background Breast reconstruction is associated with multiple risk factors for
      venous thromboembolism. However, the incidence of deep vein thrombosis in
      patients undergoing breast reconstruction is uncertain. Objective The aim of this
      study was to prospectively evaluate the incidence of deep vein thrombosis in
      patients undergoing breast reconstruction using autologous tissue transfer and to
      identify potential risk factors for deep vein thrombosis. Methods Thirty-five
      patients undergoing breast reconstruction were enrolled. We measured patients'
      preoperative characteristics including age, body mass index (kg/m2), and risk
      factors for deep vein thrombosis. The preoperative diameter of each venous
      segment in the deep veins was measured using duplex ultrasound. All patients
      received intermittent pneumatic pump and elastic compression stockings for
      postoperative thromboprophylaxis. Results Among the 35 patients evaluated, 11
      (31.4%) were found to have deep vein thrombosis postoperatively, and one patient
      was found to have pulmonary embolism postoperatively. All instances of deep vein
      thrombosis developed in the calf and were asymptomatic. Ten of 11 patients
      underwent free flap transfer, and the remaining one patient received a latissimus
      dorsi pedicled flap. Deep vein thrombosis incidence did not significantly differ
      between patients with a free flap or pedicled flap (P = 0.13). Documented risk
      factors for deep vein thrombosis demonstrated no significant differences between
      patients with and without deep vein thrombosis. The diameter of the common
      femoral vein was significantly larger in patients who developed postoperative
      deep vein thrombosis than in those who did not ( P < 0.05). Conclusions The
      morbidity of deep vein thrombosis in patients who underwent breast reconstruction
      using autologous tissue transfer was relatively high. Since only the diameter of
      the common femoral vein was predictive of developing postoperative deep vein
      thrombosis, postoperative pharmacological thromboprophylaxis should be considered
      for all patients undergoing breast reconstruction regardless of operative
      procedure.

PMID- 27864562
TI  - Response to letter: Long-term follow-up results of patients undergoing
      transjugular coil embolisation.

PMID- 27864564
TI  - Hierarchical structure and importance of patients' reasons for treatment choices
      in knee and hip osteoarthritis: a concept mapping study.
AB  - OBJECTIVES: To improve patients' use of conservative treatment options of hip and
      knee OA, in-depth understanding of reasons underlying patients' treatment choices
      is required. The current study adopted a concept mapping method to thematically
      structure and prioritize reasons for treatment choice in knee and hip OA from a
      patients' perspective. METHODS: Multiple reasons for treatment choices were
      previously identified using in-depth interviews. In consensus meetings, experts
      derived 51 representative reasons from the interviews. Thirty-six patients
      individually sorted the 51 reasons in two card-sorting tasks: one based on
      content similarity, and one based on importance of reasons. The individual
      sortings of the first card-sorting task provided input for a hierarchical cluster
      analysis (squared Euclidian distances, Ward's method). The importance of the
      reasons and clusters were examined using descriptive statistics. RESULTS: The
      hierarchical structure of reasons for treatment choices showed a core distinction
      between two categories of clusters: barriers [subdivided into context (e.g. the
      healthcare system) and disadvantages] and outcome (subdivided into treatment and
      personal life). At the lowest level, 15 clusters were identified of which the
      clusters Physical functioning, Risks and Prosthesis were considered most
      important when making a treatment decision for hip or knee OA. CONCLUSION:
      Patients' treatment choices in knee and hip OA are guided by contextual barriers,
      disadvantages of the treatment, outcomes of the treatment and consequences for
      personal life. The structured overview of reasons can be used to support shared
      decision-making.

PMID- 27864563
TI  - A replication study and meta-analysis of mitochondrial DNA variants in the
      radiographic progression of knee osteoarthritis.
AB  - OBJECTIVE: To conduct a replication study and meta-analysis involving the study
      of mtDNA variants in the radiographic progression of OA in different cohorts
      worldwide, including Cohort Hip and Cohort Knee (CHECK), the OA Initiative and a
      cohort from Spain. METHODS: The influence of the haplogroups in the rate of
      radiographic progression at 96 months in 431 subjects from CHECK was assessed in
      terms of Kellgren and Lawrence (KL) grade. Progression was defined as a change
      from KL ? 1 at baseline to any higher grade during the follow-up. Extended Cox
      proportional hazard models were used to analyse the influence of mtDNA variants
      in the rate of radiographic knee OA progression. A subsequent meta-analysis of
      1603 subjects following the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses guidelines was conducted to combine the data of individual studies.
      A sensitivity analysis was performed to validate the stability of the results.
      RESULTS: CHECK subjects carrying the haplogroup T showed the lowest rate of
      radiographic knee OA progression [hazard ratio (HR) 0.645 (95% CI 0.419, 0.978);
      P < 0.05]. When pooled, subjects within the superhaplogroup JT showed the same
      trend [HR 0.707 (95% CI 0.501, 0.965); P < 0.05]. BMI [HR 1.046 (95% CI 1.018,
      1.073); P < 0.05] and bilateral OA [HR 2.266 (95% CI 1.733, 2.954); P < 0.05] at
      baseline are risk factors for radiographic knee OA progression as well. In the
      meta-analysis there was a reduced rate of radiographic progression in subjects
      with haplogroup T [HR 0.612 (95% CI 0.454, 0.824); P = 0.001] or in the
      superhaplogroup JT [HR 0.765 (95% CI 0.624, 0.938); P = 0.009]. Sensitivity
      analysis revealed that the results were robust. CONCLUSION: The mtDNA variants in
      the superhaplogroup JT associate with a reduced rate of radiographic OA
      progression. The mtDNA polymorphisms in the superhaplogroup JT emerge as
      potential complementary genetic biomarkers for disease progression.

PMID- 27864566
TI  - Using Practice-Based Evidence to Improve Supportive Care Practices to Reduce
      Central Line-Associated Bloodstream Infections in a Pediatric Oncology Unit
      [Formula: see text].
AB  - Children with cancer are a subset of patients with central lines with distinct
      risk factors for infection including periods of prolonged neutropenia and
      compromised mucous membrane integrity. This article relates the implementation of
      principles of practice-based evidence to identify interventions in addition to
      best practice maintenance care bundles to reduce central line-associated
      bloodstream infections involving viridans group streptococci and coagulase
      negative staphylococci on an inpatient pediatric oncology unit. Review of
      individual events combined with review of current clinical practice guided the
      development of structured protocols emphasizing routine oral care and general
      supportive cares. Key principles of the protocols emphasized a 1-2-3 mnemonic and
      included daily bathing, twice daily oral care, and out-of-bed activity 3 times
      daily. Poisson regression identified a significant main effect for time period
      for central line-associated bloodstream infection rates involving both viridans
      group streptococci and coagulase-negative staphylococci. Significant differences
      were present between the preintervention baseline and implementation of the
      supportive care protocols. Project outcomes demonstrate the added value of using
      principles of practice-based evidence to guide the development of interventions
      to improve clinical care when evidence-based sources are limited.

PMID- 27864567
TI  - Remembering to learn: the overlooked role of remembrance in safety improvement.

PMID- 27864565
TI  - Targeting non-canonical nuclear factor-kappaB signalling attenuates
      neovascularization in a novel 3D model of rheumatoid arthritis synovial
      angiogenesis.
AB  - OBJECTIVE: Angiogenesis is crucial in RA disease progression. Lymphotoxin beta
      receptor (LTbetaR)-induced activation of the non-canonical nuclear factor-kappaB
      (NF-kappaB) pathway via NF-kappaB-inducing kinase (NIK) has been implicated in
      this process. Consequently, inhibition of this pathway may hold therapeutic
      potential in RA. We describe a novel three-dimensional (3D) model of synovial
      angiogenesis incorporating endothelial cells (ECs), RA fibroblast-like
      synoviocytes (RAFLSs) and RA synovial fluid (RASF) to further investigate the
      contributions of NF-kappaB in this process. METHODS: Spheroids consisting of
      RAFLSs and ECs were stimulated with RASF, the LTbetaR ligands LTbeta and LIGHT,
      or growth factor bFGF and VEGF, followed by quantification of EC sprouting using
      confocal microscopy and digital image analysis. Next, the effects of anginex, NIK
      targeting siRNA (siNIK), LTbetaR-Ig fusion protein (baminercept) and a novel
      pharmacological NIK inhibitor were investigated. RESULTS: RASF significantly
      promoted sprout formation, which was blocked by the established angiogenesis
      inhibitor anginex (P < 0.05). LTbeta and LIGHT induced significant sprouting (P <
      0.05), as did bFGF/VEGF (P < 0.01). siNIK pre-treatment of ECs led to reductions
      in LTbetaR-induced vessel formation (P < 0.05). LTbetaR-Ig not only blocked
      LTbeta- or LIGHT-induced sprouting, but also RASF-induced sprouting (P < 0.05).
      The NIK inhibitor blocked angiogenesis induced by LTbeta, LIGHT, growth factors
      (P < 0.05) and RASF (P < 0.01). CONCLUSION: We present a novel 3D model of
      synovial angiogenesis incorporating RAFLSs, ECs and RASF that mimics the in vivo
      situation. Using this system, we demonstrate that non-canonical NF-kappaB
      signalling promotes neovascularization and show that this model is useful for
      dissecting relative contributions of signalling pathways in specific cell types
      to angiogenic responses and for testing pharmacological inhibitors of
      angiogenesis.

PMID- 27864568
TI  - Value of dynamic MRI using the Ktrans technique for assessment of native kidneys
      in pre-emptive renal transplantation.
AB  - Background Different non-invasive imaging techniques such as Doppler
      ultrasonography and renal scintigraphy are commonly employed to assess allograft
      function and associated complications. However, all such methods lack sufficient
      specificity to discriminate between residual renal function of native kidneys.
      Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluates signal
      dynamics during the passage of contrast material through the renal cortex,
      medulla, and collecting system. Purpose To investigate the value of DCE 3T MRI
      using a quantitative pharmacokinetic parameter (Ktrans) for the assessment of
      native kidneys before and after pre-emptive renal transplantation. Material and
      Methods Twenty-five consecutive patients with end-stage renal disease underwent
      DCE MRI before and 6 months after kidney transplantation. MRI was performed using
      a 3T scanner. Regions of interests were drawn over each kidney, encompassing the
      cortex and medulla but excluding the collecting system and any coexisting cysts.
      Parametric Ktrans values were automatically generated. Results In the pre
      transplantation group, mean Ktrans values for the right and left kidneys were
      0.55 +/- 0.09 min-1 and 0.44 +/- 0.15 min-1, respectively. In the post
      transplantation group, mean Ktrans values of the right and left kidneys were 0.27
      +/- 0.07 min-1 and 0.25 +/- 0.10 min-1, respectively. There were statistically
      significant differences between right and left kidneys in terms of mean Ktrans
      values in the pre- and post-transplantation groups ( P < 0.001). Conclusion Our
      preliminary results show that native kidneys were still functioning 6 months
      after transplantation. MR perfusion using Ktrans may constitute a non-invasive
      means of determination of the viability of native kidneys after renal
      transplantation.

PMID- 27864569
TI  - Repeated self-harm in young people: a review.
AB  - OBJECTIVES: This paper provides a review of the rates of self-harm and repeated
      self-harm among young people. It describes some of the risk factors associated
      with these behaviours and summarises some of the barriers to delivering optimal
      treatment. CONCLUSIONS: The review concludes that there is an urgent need for the
      delivery of respectful and evidence-based practice to all young people who
      present with self-harm. In addition, improved monitoring of self-harm
      presentations to hospitals across Australia is required in order that robust data
      are collected and the impact of practice change can be reliably assessed.

PMID- 27864570
TI  - Comparing Help-Seeking Behavior of Male and Female Survivors of Sexual Assault: A
      Content Analysis of a Hotline.
AB  - This content analysis examines written documentation of telephone calls to a
      regional sexual assault hotline over a 5-year period. All male callers identified
      as primary victims were selected for analysis ( n = 58) and a corresponding
      sample of female primary victims ( n = 58) were randomly selected for comparison
      to better understand the help-seeking behavior of sexual assault survivors and
      inform services accordingly. A summative content analysis revealed significant
      contrasting themes between male and female victims, including females
      significantly receiving more referrals and males accessing the hotline to tell
      their experience of being sexually assaulted due to perceived limited support.
      Implications for training, practice, and future research are discussed.

PMID- 27864571
TI  - The Relationship Between Coach and Player Training Load Perceptions in
      Professional Soccer.
AB  - The training load imposed and perceived by coaches and soccer players,
      respectively, was compared for three weeks of the basic preparatory period of a
      professional soccer team through session ratings of perceived exertion (S-RPE).
      Participants were 24 professional Brazilian soccer players (all males, age: 24.1
      +/- 3.4 years) and their coaches. Athletes responded to the scale of perceived
      exertion (scores from 0 to10) after the training, while the coaches completed the
      scale prior to the training session, based on prior planning. The t-test for
      independent samples was used to compare S-RPE responses, and the Pearson
      correlation test was used to examine possible correlations between the parameters
      analyzed. There were no statistical differences between perceptions of prescribed
      (coaches) and experienced (players) S-RPE, and moderate correlations were found
      between these parameters ( r = .60; p = .003). No statistically significant group
      differences were found in the perceived exertion during any of three types of
      training: physical, technical, or tactical. The results suggest that the S-RPE
      prescribed during the preseason period (by coaches) was not different from that
      perceived by professional soccer players.

PMID- 27864572
TI  - Models of health behaviour predict intention to use long acting reversible
      contraception use.

PMID- 27864573
TI  - Multi-Level Assessment to Reach Out to Rural Breast Cancer Survivors.

PMID- 27864575
TI  - Tumor Humor?

PMID- 27864576
TI  - A Case of Nivolumab-Induced Myositis.

PMID- 27864574
TI  - Enhancing Endocrine Therapy Combination Strategies for the Treatment of
      Postmenopausal HR+/HER2- Advanced Breast Cancer.
AB  - : Breast cancer (BC) is the most common malignancy in women worldwide, with
      approximately two-thirds having hormone receptor-positive (HR+) tumors. New
      endocrine therapy (ET) strategies include combining ET agents as well as adding
      inhibitors targeting growth factors, angiogenesis, the mechanistic target of
      rapamycin, phosphoinositide 3-kinase (PI3K), or cyclin-dependent kinase 4/6 to
      ET. Level 1 evidence supports use of fulvestrant plus anastrozole or palbociclib
      plus letrozole as first-line therapy for HR+/HER- advanced BC with special
      consideration for the former in ET-naive patients, as well as everolimus plus
      exemestane or palbociclib plus fulvestrant as second-line therapy with special
      consideration in select first-line patients. Although the safety profiles of
      these combinations are generally predictable and manageable, both everolimus and
      palbociclib are associated with an increased risk of potentially serious or early
      onset toxicities requiring individualized a priori adverse event risk
      stratification, earlier and more rigorous agent-specific monitoring, and patient
      education. Although each of these combinations improves progression-free
      survival, none with the exception of anastrazole plus fulvestrant have
      demonstrated improved overall survival. PI3K catalytic-alpha mutations assessed
      from circulating tumor DNA represent the first potentially viable serum biomarker
      for the selection of ET combinations, and new data demonstrate the feasibility of
      this minimally invasive technique as an alternative to traditional tissue
      analysis. Therapeutic ratios of select ET combinations support their use in first
      and second-line settings, but optimal sequencing has yet to be determined. THE
      ONCOLOGIST: 2017;22:12-24 IMPLICATIONS FOR PRACTICE: Emerging data show that new
      endocrine therapy (ET) combinations can improve progression-free and overall
      survival outcomes in patients with hormone receptor-positive, HER2-negative
      (HR+/HER-) advanced breast cancer. Level 1 evidence supports consideration of
      dual ET regimens, particularly in ET-naive patients, or palbociclib plus
      letrozole as first-line therapy, as well as the addition of mTOR or CDK4/6
      inhibitors to established ET in the second-line setting and in select first-line
      patients. Some combinations are associated with increased risk of class-specific
      toxicities that will require individualized risk stratification, earlier and more
      rigorous agent-specific monitoring, and patient education. Recent data on a
      noninvasive biomarker assay that predicts response to a phosphoinositide 3-kinase
      inhibitor demonstrates the feasibility of this minimally invasive technique as an
      alternative to traditional tissue analysis.

PMID- 27864577
TI  - Diagnosing necrotic meningioma: a distinctive imaging pattern in diffusion MRI
      and MR spectroscopy.
AB  - The differential diagnosis of necrotic meningiomas includes brain abscess and
      malignant neoplasms. We report and discuss hereby the work-up of two patients
      diagnosed with necrotic meningioma using diffusion-weighted imaging, magnetic
      resonance spectroscopy, resective surgery, and histopathology. The purpose of the
      present article is to add to the scant literature on the use of advanced imaging
      modalities in the routine investigation of brain lesions and their utility in
      arriving at the final diagnosis.

PMID- 27864580
TI  - Farewell 2016, it's been swell!

PMID- 27864579
TI  - Automated segmentation reveals silent radiographic progression in adult-onset
      vanishing white-matter disease.
AB  - Adult-onset vanishing white-matter disease (VWM) is a rare autosomal recessive
      disease with neurological symptoms such as ataxia and paraparesis, showing
      extensive white-matter hyperintensities (WMH) on magnetic resonance (MR) imaging.
      Besides symptom-specific scores like the International Cooperative Ataxia Rating
      Scale (ICARS), there is no established tool to monitor disease progression.
      Because of extensive WMH, visual comparison of MR images is challenging. Here, we
      report the results of an automated method of segmentation to detect alterations
      in T2-weighted fluid-attenuated-inversion-recovery (FLAIR) sequences in a one
      year follow-up study of a clinically stable patient with genetically diagnosed
      VWM. Signal alterations in MR imaging were quantified with a recently published
      WMH segmentation method by means of extreme value distribution (EVD). Our
      analysis revealed progressive FLAIR alterations of 5.84% in the course of one
      year, whereas no significant WMH change could be detected in a stable multiple
      sclerosis (MS) control group. This result demonstrates that automated EVD-based
      segmentation allows a precise and rapid quantification of extensive FLAIR
      alterations like in VWM and might be a powerful tool for the clinical and
      scientific monitoring of degenerative white-matter diseases and potential
      therapeutic interventions.

PMID- 27864581
TI  - Prognostic Value of Diffusion-Weighted Imaging (DWI) Apparent Diffusion
      Coefficient (ADC) in Patients with Hyperacute Cerebral Infarction Receiving rt-PA
      Intravenous Thrombolytic Therapy.
AB  - BACKGROUND The aim of this study was to investigate the potential value of
      apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in the
      prognosis of patients with hyperacute cerebral infarction (HCI) receiving
      intravenous thrombolytic therapy with recombinant tissue plasminogen activator
      (rt-PA). MATERIAL AND METHODS From June 2012 to June 2015, 58 cases of HCI (<6 h)
      undergoing rt-PA intravenous thrombolytic therapy (thrombolysis group) and 70
      cases of HCI (<6 h) undergoing conventional antiplatelet and anticoagulant
      therapy (control group) in the same period were collected. DWI was conducted on
      all the subjects, and ADC maps were generated with Functool software to quantify
      ADC value. The clinical outcomes of HCI patients were observed for 3 months, and
      prognostic factors were analyzed. RESULTS Before thrombolysis treatment, the
      lesion area presented high signal intensity on DWI map and low signal intensity
      on ADC map, and gradually weakened signal intensity on DWI map and gradually
      enhanced signal intensity on ADC map were observed after thrombolysis. The ADC
      values of the thrombolysis group were significantly higher than those of the
      control group after treatment (24 h, 7 d, 30 d, and 90 d) (all P<0.05), and the
      ADC and rADC values in the thrombolysis group gradually increased over time (all
      P<0.05). Multiple logistic regression analysis showed that baseline National
      Institutes of Health Stroke Scale (NIHSS) score, baseline rADC value, and stroke
      history were the independent factors for the prognosis of HIC patients with
      thrombolysis (all P<0.05). CONCLUSIONS The values of ADC and rADC may provide
      guidance in the prognosis of HCI patients receiving rt-PA, and the baseline rADC
      value is the protective factor for the prognosis of HCI patients receiving rt-PA.

PMID- 27864578
TI  - Mesoscopic imaging of glioblastomas: Are diffusion, perfusion and spectroscopic
      measures influenced by the radiogenetic phenotype?
AB  - The purpose of this study was to identify markers from perfusion, diffusion, and
      chemical shift imaging in glioblastomas (GBMs) and to correlate them with
      genetically determined and previously published patterns of structural magnetic
      resonance (MR) imaging. Twenty-six patients (mean age 60 years, 13 female) with
      GBM were investigated. Imaging consisted of native and contrast-enhanced 3D data,
      perfusion, diffusion, and spectroscopic imaging. In the presence of minor
      necrosis, cerebral blood volume (CBV) was higher (median +/- SD, 2.23% +/- 0.93)
      than in pronounced necrosis (1.02% +/- 0.71), pcorr = 0.0003. CBV adjacent to
      peritumoral fluid-attenuated inversion recovery (FLAIR) hyperintensity was lower
      in edema (1.72% +/- 0.31) than in infiltration (1.91% +/- 0.35), pcorr = 0.039.
      Axial diffusivity adjacent to peritumoral FLAIR hyperintensity was lower in
      severe mass effect (1.08*10-3 mm2/s +/- 0.08) than in mild mass effect (1.14*10-3
      mm2/s +/- 0.06), pcorr = 0.048. Myo-inositol was positively correlated with a
      marker for mitosis (Ki-67) in contrast-enhancing tumor, r = 0.5, pcorr = 0.0002.
      Changed CBV and axial diffusivity, even outside FLAIR hyperintensity, in adjacent
      normal-appearing matter can be discussed as to be related to angiogenesis
      pathways and to activated proliferation genes. The correlation between myo
      inositol and Ki-67 might be attributed to its binding to cell surface receptors
      regulating tumorous proliferation of astrocytic cells.

PMID- 27864582
TI  - [Skin diseases due to systemic vasculitides and vasculopathies].
AB  - Vasculitis and vasculopathy are two distinct disease entities. Each entity
      comprises a large number of heterogeneous diseases, which can occur alone or
      associated with autoimmune, infectious or neoplastic diseases. The terms
      vasculitis and vasculopathy are often falsely used synonymously. A vasculitis
      initially causes inflammation of the vessel walls that may result in a secondary
      occlusion. In contrast, a vasculopathy is a primary occlusion of the vascular
      lumen, which is followed by inflammation after ischemia and ulceration. In most
      patients the distinction can be made based on the clinical presentation. A clear
      clinical diagnosis is then followed by targeted serological, histological and
      imaging procedures to confirm the clinical diagnosis. On this basis a well
      founded treatment can be initiated. In the presence of vasculitis an anti
      inflammatory therapy is indicated, whereas in the case of vasculopathy, removal
      of the vascular occlusion is the main focus. This article provides an overview of
      the various diseases and addresses the pathogenetic and clinical characteristics
      used to differentiate the individual disease entities. It also provides an
      insight into the therapy options and prophylaxis.

PMID- 27864584
TI  - Reminiscence of Forty Years of Environmental Chemistry.

PMID- 27864583
TI  - Removal and Biodegradation of Phenanthrene, Fluoranthene and Pyrene by the Marine
      Algae Rhodomonas baltica Enriched from North Atlantic Coasts.
AB  - This study is focused on the removal, accumulation and degradation of three
      environmental ubiquitous polycyclic aromatic hydrocarbons (PAHs), phenanthrene
      (PHE), fluoranthene (FLA) and pyrene (PYR), by the marine alga Rhodomonas baltica
      enriched from the English Channel. After separation, purification and culture in
      several phases, R. baltica was exposed to PAH concentrations that are frequently
      encountered in the field in several anthropized environments. The results showed
      that R. baltica can grow under PAH stress, efficiently remove up to 70% of these
      compounds from the medium by 216 h of culture and selectively bioaccumulate PAHs
      by their hydrophobicity. Between PHE, FLA and PYR, phenanthrene was the compound
      with higher degradation rates throughout incubation. The equilibrium partitioning
      theoretical approach showed that physico-chemical partitioning, rather than
      active bioconcentration, was the major factor governing the bioaccumulation,
      outlying a potential application in decontamination processes for this species.

PMID- 27864585
TI  - Changes in Glutathione S-Transferase Activity and Parental Care Patterns in a
      Catfish (Pisces, Ariidae) as a Biomarker of Anthropogenic Impact in a Brazilian
      Harbor.
AB  - Catfish have been used as a model system for studying biochemical mechanisms of
      biotransformation. The main goal of this study was to identify alterations in
      hepatic glutathione S-transferase (GST) activity and changes in the parental care
      pattern of a mouth-brooding catfish, Sciades herzbergii, as a biomarker of
      anthropogenic impact in a port area on the northeastern coast of Brazil. The fish
      were sampled from a natural reserve (A1 = reference site) and from an
      industrialized port area (A2 = impacted site). Two analyses were carried out:
      hepatic GST activity and mouth-brooding behavior of males. Catfish collected from
      the A1 site displayed all stages of gonadal maturation, and some of the adult
      males were mouth brooding 12-30 embryos. Not all gonadal maturation stages of the
      catfish were represented at the A2 site, and no mouth-brooding males were
      observed. GST activity in the liver of S. herzbergii was significantly higher in
      fish from the impacted site compared with fish from the reference site. Values
      for the enzymatic activity increased progressively in fish sampled from the
      reserve area as they became more reproductively mature (immature <= maturing <=
      mature <= spent). However, the greatest values for GST activity (2.84 +/- 0.31
      MUmol min-1 mg protein-1) among fish sampled from the impacted area were found in
      (immature) juveniles. These data suggest that changes in hepatic GST activity and
      mouth-brooding behavior of S. herzbergii can be used as biomarkers of
      anthropogenic impact.

PMID- 27864586
TI  - Lifetime prevalence of and factors associated with non-traumatic musculoskeletal
      pains amongst surgeons and patients.
AB  - PURPOSE: There is evidence that surgeons make different recommendations for
      people seeking their care than they make for themselves. There may also be
      differences in pain episodes and management strategies between surgeons and
      people seeking care, knowledge of which might improve care. We aimed to assess
      whether the prevalence of non-traumatic pains, treatments and other factors
      differed between patients and surgeons. MATERIALS AND METHODS: Two-hundred and
      twenty surgeons, members of the Science of Variation Group (SOVG), and 248
      patients seeking care at the Hand Service at a large academic hospital completed
      a survey regarding the lifetime incidence of non-traumatic pains lasting > one
      month using short versions of the Pain Catastrophising Scale (PCS-4); Patient
      Health Questionnaire (PHQ-2); and Short Health Anxiety Inventory (SHAI-5).
      RESULTS: Surgeons had a higher prevalence of at least one non-traumatic pain than
      patients and were more likely to report pain at more than one anatomical site.
      Patients were more likely to receive any treatment: surgery; injection; non
      opioid medication; opioid medication; physical or occupational therapy. Patients
      missed work more often than surgeons. Age was the only factor independently
      associated with patient pain. Practicing in the United States was the only factor
      independently associated with surgeon pain. CONCLUSIONS: Non-traumatic pains are
      extremely common. Surgeons have particularly effective coping strategies,
      allowing them to maintain their life roles with limited medical care when in
      pain. Increasing the appeal and availability of methods for optimising coping
      strategies might help to narrow the gap between surgeon and patient health.

PMID- 27864587
TI  - Evaluation of the genetic basis of primary hypoadrenocorticism in Standard
      Poodles using SNP array genotyping and whole-genome sequencing.
AB  - Primary hypoadrenocorticism, also known as Addison's disease, is an autoimmune
      disorder leading to the destruction of the adrenal cortex and subsequent loss of
      glucocorticoid and mineralocorticoid hormones. The disease is prevalent in
      Standard Poodles and is believed to be highly heritable in the breed. Using
      genotypes derived from the Illumina Canine HD SNP array, we performed a genome
      wide association study of 133 carefully phenotyped Standard Poodles (61 affected,
      72 unaffected) and found no markers significantly associated with the disease. We
      also sequenced the entire genomes of 20 Standard Poodles (13 affected, 7
      unaffected) and analyzed the data to identify common variants (including SNPs,
      indels, structural variants, and copy number variants) across affected dogs and
      variants segregating within a single pedigree of highly affected dogs. We
      identified several candidate genes that may be fixed in both Standard Poodles and
      a small population of dogs of related breeds. Further studies are required to
      confirm these findings more broadly, as well as additional gene-mapping efforts
      aimed at fully understanding the genetic basis of what is likely a complex
      inherited disorder.

PMID- 27864588
TI  - Impact of perioperative hypoglycaemia in subjects with diabetes undergoing
      colorectal surgery.
AB  - INTRODUCTION: This study explores the association between perioperative
      hypoglycaemia and surgical outcomes in subjects with diabetes, undergoing
      colorectal surgery. METHODS: A retrospective review of 149 subjects with Type 2
      Diabetes Mellitus (DM) who underwent colorectal surgery between 2010 and 2015 was
      performed. Perioperative glucose levels, glycated haemoglobin (HbA1c)
      measurements within 3 months of surgery and surgical complications based on
      Clavien-Dindo classification were analysed. RESULTS: The mean age was 67 years
      (67 +/- 11.2). Perioperative hypoglycaemia was found in 7.4% of subjects. The
      mean HbA1c of subjects with Clavien 2 and above surgical complications were
      higher than patients with Clavien 1 or no complications, Hba1c 7.6% (7.6 +/-
      2.5%) and 7.0% (7.0 +/- 1.1%, p = 0.008), respectively. Similar findings in
      subjects with Clavien 3 and above complications, HbA1c of 8.2% (8.2 +/- 3.9%) as
      compared to those with Clavien 2 and below complications, 7.2% (7.2 +/- 1.5%, p =
      0.001). Adjusted multivariate analysis showed that hypoglycaemia was
      significantly associated with Clavien 2 and above surgical complications, OR of
      19.0 (CI 2.23-162, p = 0.007). Preoperative hypoglycaemia was associated with
      Clavien 2 and above surgical complications, OR 10.7 (CI 1.22-94.1, p = 0.032).
      Suboptimal glycaemic control (Hba1c >8.0%) was significantly associated with
      Clavien 2 and above complications, OR 2.48 (CI 1.04-5.91, p = 0.04), but not with
      Clavien 3 and above complications, OR 1.50 (CI 0.450-4.98, p = 0.511).
      CONCLUSION: Perioperative hypoglycaemia is associated with adverse surgical
      outcomes in diabetic patients undergoing colorectal surgery. Prevention of
      hypoglycaemia may improve surgical outcomes. HbA1c is an independent predictor
      for adverse surgical outcomes.

PMID- 27864589
TI  - Functionality of Tn916 in Paenibacillus larvae.
AB  - The conjugative transposon Tn916 was determined to be functional in Paenibacillus
      larvae in regard to expression of tetracycline resistance and conjugative
      transfer. Expression of erythromycin resistance, using Tn916DeltaE, was also
      observed. Conjugative transfer experiments employing Paenibacillus popilliae
      strains Tc1001 and Em1001 as transposon donors and experiments using different P.
      larvae subspecies or different transposon-containing strains demonstrated
      interspecies and intraspecies transfer occurred for Tn916 and Tn916DeltaE.
      Southern hybridization analysis of several Tn916-containing P. larvae isolates
      showed that the transposon randomly inserted into the bacterial chromosome with
      an indication that hot spot insertion had occurred. Hybridization analysis
      indicated single-copy insertion of Tn916 into the genome predominated. However,
      selection of multiple-resistant isolates (i.e., isolates containing Tn916 and
      Tn916DeltaE) demonstrated that multiple copies of the transposon could coexist in
      the bacterial genome. Growth of transposon-containing isolates in broth medium in
      the absence of selective antibiotic pressure showed that Tn916 and Tn916DeltaE
      were stably maintained in the bacterium.

PMID- 27864590
TI  - Do we need FDG-PET/CT to assess atherosclerosis?

PMID- 27864591
TI  - Comparison of S.T.O.N.E and CROES nephrolithometry scoring systems for predicting
      stone-free status and complication rates after percutaneous nephrolithotomy: a
      single center study with 262 cases.
AB  - The aim of this study was to compare the accuracy of the CROES nephrolithometric
      nomogram and S.T.O.N.E. scoring system in predicting PCNL outcomes in terms of
      stone-free rate, estimated blood loss (EBL), operative time (OR), length of
      hospital stay (LOS), and complications. Patients who underwent PCNL for renal
      stones between May 2012 and January 2015 were analyzed retrospectively. The
      patients' demographic characteristics and operational features were recorded
      prospectively in all patients postoperatively. S.T.O.N.E. and CROES
      nephrolithometry scores' correlation with stone-free status, operation and
      fluoroscopy time, length of hospital stay (LOS) and blood loss (BL) was
      evaluated. Patients were categorized according to S.T.O.N.E. nephrolithometry and
      CROES nephrolithometry scores. Postoperative complications were graded according
      to modified Clavien classification (Dindo et al. in Ann Surg 240:205-213, 2004)
      and the correlation of both scoring systems with postoperative complications was
      also evaluated. We identified 437 patients who underwent PCNL between May 2012
      and January 2015. A total of 262 patients who are available data for the CROES
      and S.T.O.N.E. scoring systems were included in the recent study. The mean
      S.T.O.N.E score was 7.65 +/- 1.56 and the mean CROES score was 191.13 +/- 64.39.
      The overall stone-free rate was 71.4%. Of the 262 patients, 89 experienced
      postoperative complications. Stone-free patients had significantly lower BMI
      (<0.001) and stone burden (p < 0.001). Regression analysis showed that both
      scoring systems were significantly associated with stone-free rates and operation
      time. We demonstrated that S.T.O.N.E. and CROES scoring systems were useful for
      predicting post-PCNL stone-free status. But both scoring systems were not useful
      for predicting post-PCNL complications.

PMID- 27864592
TI  - Evaluation of 5-fluorouracil degradation rate and Pharmacogenetic profiling to
      predict toxicity following adjuvant Capecitabine.
AB  - BACKGROUND: On account of the lack of predictive biomarkers of toxicity, we
      investigated whether polymorphisms of genes involved in fluoropyrimidine
      metabolism and 5-fluorouracil (5-FU) degradation rate were associated with
      outcomes of adjuvant capecitabine in patients with early stage gastrointestinal
      cancers. METHODS: Genotyping of DPYD GIVS14A, MTHFR C677T and A1298C SNPs were
      performed by pyro-sequencing technology. PCR analysis was used for genotyping
      TYMS-TSER. We also evaluated the 5-FU degradation rate, which determines the
      amount of drug consumed by PBMC in a time unit. Association of these variables
      with clinical outcome was evaluated using multivariate logistic regression
      analysis. RESULTS: One hundred forty-two patients with early stage colon (39%),
      rectal (28%), stomach (20%) and pancreatic (13%) cancer, treated with adjuvant
      capecitabine, were included in this retrospective analysis. Seventy and 20% of
      the patients suffered from at least one G1-4 and G3-4 adverse events,
      respectively. According to the 5-FU degradation rate, three and 13 patients were
      assigned as poor (<0.86 ng/mL/106 cells/min) and ultra-rapid (>2.1 ng/mL/106
      cells/min) metabolizers, respectively. At a multivariate logistic regression
      analysis, an altered 5-FU degradation rate (values <0.86 or >2.10 ng/mL/106
      cells/min) was associated with grade 3-4 adverse events (OR = 2.09, 95% CI: 1.14
      3.82, P = 0.01). No correlation was reported between toxicity and gene
      polymorphisms except for hand-foot syndrome that was more frequent in the MTHFR
      1298CC homozygous variant genotype (OR = 2.03, 95% CI 1.04-3.96, P = 0.03).
      CONCLUSIONS: 5-FU degradation rate may be regarded as possible predictive
      biomarker of capecitabine toxicity in early stage gastrointestinal cancer.

PMID- 27864593
TI  - Toxicogenomics in Environmental Science.
AB  - This chapter reviews the current knowledge and recent progress in the field of
      environmental, aquatic ecotoxicogenomics with a focus on transcriptomic methods.
      In ecotoxicogenomics the omics technologies are applied for the detection and
      assessment of adverse effects in the environment, and thus are to be
      distinguished from omics used in human toxicology [Snape et al., Aquat Toxicol
      67:143-154, 2004]. Transcriptomic methods in ecotoxicology are applied to gain a
      mechanistic understanding of toxic effects on organisms or populations, and thus
      aim to bridge the gap between cause and effect. A worthwhile effect-based
      interpretation of stressor induced changes on the transcriptome is based on the
      principle of phenotypic-anchoring [Paules, Environ Health Perspect 111:A338-A339,
      2003]. Thereby, changes on the transcriptomic level can only be identified as
      effects if they are clearly linked to a specific stressor-induced effect on the
      macroscopic level. By integrating those macroscopic and transcriptomic effects,
      conclusions on the effect-inducing type of the stressor can be drawn. Stressor
      specific effects on the transcriptomic level can be identified as stressor
      specific induced pathways, transcriptomic patterns, or stressors-specific genetic
      biomarkers. In this chapter, examples of the combined application of macroscopic
      and transcriptional effects for the identification of environmental stressors,
      such as aquatic pollutants, are given and discussed. By means of these examples,
      challenges on the way to a standardized application of transcriptomics in
      ecotoxicology are discussed. This is also done against the background of the
      application of transcriptomic methods in environmental regulation such as the EU
      regulation Registration, Evaluation, Authorisation and Restriction of Chemicals
      (REACH).

PMID- 27864594
TI  - Morphologic classification of the right auricule on 256-slice computed
      tomography.
AB  - PURPOSE: To investigate the shape of right auricule on 256-slice computed
      tomography (CT). MATERIALS AND METHODS: Five hundred people (250 men, age range
      16-84 years) who had cardiac multidetector CT angiography were recruited in this
      study. All patients had normal sinus rhythm with normal blood pressure (<140/90
      mmHg for systolic/diastolic pressure). The morphology of the right auricule was
      studied and compared after reconstruction of the raw images. RESULTS: All
      patients successfully had cardiac CT angiography (100%), and the right auricule
      morphology was divided into five types and nine subtypes, including Type I of
      triangular shape (Ia and Ib), Type II of M shape (IIa and IIb), Type III of L
      shape (IIIa and IIIb), Type IV of reverse L shape (IVa and IVb), and Type V of
      balanced shape. The most common type of right auricule is Type IV (28.4%)
      followed by Type II (24.0%), whereas the least common is Type V (11.0%). Type Ia
      was present significantly (P < 0.0001) more frequently in females than in males,
      whereas Type IIa significantly (P = 0.042) more frequently in males than females.
      No other significant (P > 0.05) sex difference existed in the constitution ratio
      of the types. The normal angle was greater in Type Ib than in Ia. The greater the
      normal angle in Type I, the greater the deviation of the right auricule tip
      towards the left. CONCLUSION: A good understanding of the right auricule
      anatomical morphology can better guide atrial pacing, radiofrequency ablation and
      other surgical procedures while preventing possible intra-procedural
      complications.

PMID- 27864595
TI  - Accelerated solvent extraction combined with solid phase extraction for the
      determination of organophosphate esters from sewage sludge compost by UHPLC
      MS/MS.
AB  - Organophosphate esters (OPEs), widely used as flame retardants and plasticizers,
      are regarded as emerging pollutants. OPEs are prone to concentrate into residual
      activated sludge, which might cause secondary pollution if not suitably treated.
      Composting is an economical and effective approach to make sewage sludge stable
      and harmless. Therefore, it is essential to develop a novel method for analyzing
      OPEs in sewage sludge compost samples. However, in the composting process, large
      amounts of amendments are doped into the sludge to adjust the carbon-nitrogen
      ratio. Amendment has a strong capacity for adsorption and thus induces a decrease
      of extraction efficiency. This study developed a novel procedure for determining
      OPEs in compost samples. Accelerated solvent extraction (ASE) and solid phase
      extraction (SPE) were used for extracting and concentrating the OPEs from sewage
      sludge compost samples, and then analyzed by UHPLC-MS/MS. Some parameters were
      optimized in this study, mainly including the extraction solvent type, extraction
      temperature, static extraction time, extraction cycles, and flush volume. Under
      the optimal conditions, the proposed method showed good linearity between 0.50
      and 100 MUg kg-1 with regression coefficients in the range of 0.9984-0.9998.
      Detection limits were in the range of 0.02-3 MUg kg-1 with standard deviations
      ranging from 2 to 6%. Acceptable recoveries between 56 and 119% for samples
      spiked at different concentration levels were achieved. In contrast, the
      recoveries merely ranged from 24 to 58% by using ultrasonic-assisted extraction.
      Graphical abstract A comparison of recoveries between ultrasonic-assisted
      extraction (UAS) and accelerated solvent extraction (ASE) for organophosphate
      esters from sewage sludge compost samples.

PMID- 27864596
TI  - Motor hysteresis in a sequential grasping and pointing task is absent in task
      critical joints.
AB  - In a prior study (Schutz et al. in Exp Brain Res 2016. doi: 10.1007/s00221-016
      4608-6 ), we demonstrated that the cognitive cost of motor planning did not
      differ in a vertical pointing and grasping task. It was unclear whether the
      similar cost implied that both tasks required the same number of independent
      degrees of freedom (IDOFs) or that the number of IDOFs did not affect motor
      planning. To differentiate between both cases, a reanalysis of the prior data was
      conducted. The number of IDOFs in the pointing and grasping tasks was computed by
      factor analysis. In both tasks, two IDOFs were used, which was the minimum number
      required for position control. This indicates that hand alignment in the grasping
      task did not require an additional IDOF. No conclusions regarding the link
      between the cognitive cost of motor planning and the number of IDOFs could be
      drawn. A subset of task-critical joint angles was not affected by motor
      hysteresis. This indicates that a joint's susceptibility to motor hysteresis
      depends on its relevance to the task goal. In task-critical joints, planning cost
      minimization by motor plan reuse is suppressed in favor of the task goal.

PMID- 27864597
TI  - Genome-wide association mapping and agronomic impact of cowpea root architecture.
AB  - KEY MESSAGE: Genetic analysis of data produced by novel root phenotyping tools
      was used to establish relationships between cowpea root traits and performance
      indicators as well between root traits and Striga tolerance. Selection and
      breeding for better root phenotypes can improve acquisition of soil resources and
      hence crop production in marginal environments. We hypothesized that biologically
      relevant variation is measurable in cowpea root architecture. This study
      implemented manual phenotyping (shovelomics) and automated image phenotyping
      (DIRT) on a 189-entry diversity panel of cowpea to reveal biologically important
      variation and genome regions affecting root architecture phenes. Significant
      variation in root phenes was found and relatively high heritabilities were
      detected for root traits assessed manually (0.4 for nodulation and 0.8 for number
      of larger laterals) as well as repeatability traits phenotyped via DIRT (0.5 for
      a measure of root width and 0.3 for a measure of root tips). Genome-wide
      association study identified 11 significant quantitative trait loci (QTL) from
      manually scored root architecture traits and 21 QTL from root architecture traits
      phenotyped by DIRT image analysis. Subsequent comparisons of results from this
      root study with other field studies revealed QTL co-localizations between root
      traits and performance indicators including seed weight per plant, pod number,
      and Striga (Striga gesnerioides) tolerance. The data suggest selection for root
      phenotypes could be employed by breeding programs to improve production in
      multiple constraint environments.

PMID- 27864599
TI  - In Memory of Jay L. Grosfeld, M.D.

PMID- 27864598
TI  - Impact of fetal counseling on outcome of antenatal congenital surgical anomalies.
AB  - AIM: To analyze the impact of counseling on antenatal congenital surgical
      anomalies (ACSA). METHODS: Cases presenting with ACSA for fetal counseling and
      those presenting in post-natal period following diagnosis of ACSA (PACSA) for
      surgical opinion were analyzed for spectrum, presentation and outcome. RESULTS:
      117 cases including ACSA(68);PACSA(49) were analyzed. Gestational age at
      diagnosis of ACSA;PACSA was 17-37;17-39 weeks (median 24;32 weeks). Diagnoses in
      ACSA;PACSA included urological (26;31), neurological (10;5), congenital
      diaphragmatic hernia (CDH)(5;1), gastrointestinal (5;5), lung and chest anomalies
      (5;1), intraabdominal cysts (4;1), abdominal wall defects (4;0), tumors (3;3),
      limb anomaly (1;1), esophageal atresia (1;1), conjoint twins (1;0), hepatomegaly
      (1;0), and major cardiac anomalies (2;0). Two antenatal interventions were done
      for ACSA; vesicoamniotic shunt and amnioinfusion for oligohydramnios. 17;24
      ACSA;PACSA required early surgical intervention in post-natal period. Nine ACSA
      underwent medical termination of pregnancy and 4 had intrauterine demise. Nine
      ACSA babies died including two CDH, one gastroschisis, one duodenal atresia, one
      conjoint twins, one megacystitis with motility disorder and three posterior
      urethral valves. All PACSA babies survived. CONCLUSION: Fetal counseling for CSA
      portrays true outcome of ACSA with 32.3% (22/68) mortality versus 0% for PACSA
      due to selection bias. However, fetal counseling ensures optimal perinatal care.

PMID- 27864600
TI  - Comparison of true unenhanced and virtual unenhanced (VUE) attenuation values in
      abdominopelvic single-source rapid kilovoltage-switching spectral CT.
AB  - OBJECTIVE: To assess the agreement between the true non-contrast (TNC)
      attenuation values of intra-abdominal structures and attenuation values obtained
      on virtual-unenhanced (VUE) images based on rapid kVp-switching dual-energy CT.
      The effects of contrast phase and patient characteristics (e.g., BMI, hematocrit,
      hemoglobin content) on VUE values were also investigated. METHODS: Ninety four
      patients who underwent triphasic abdominal CT (liver mass protocol, n = 47;
      pancreas mass protocol, n = 47) between August 2014 and May 2015 were
      retrospectively reviewed. Unenhanced series was performed using conventional
      single-energy mode at 120 kVp. Late arterial and venous phase post-contrast
      series were obtained utilizing rapid kVp-switching dual-energy CT technique. VUE
      images were processed off of arterial (VUE-art) and venous (VUE-ven) phase
      series. Attenuation values of liver, pancreas, kidneys, adrenal glands, muscle,
      subcutaneous fat, aorta, IVC, and main portal vein were recorded on TNC and VUE
      sets of images. Attenuation values were compared using univariate linear
      regression and Student two-tailed paired t test. RESULTS: There was excellent
      correlation between TNC, VUE-art, and VUE-ven attenuation values across all
      organs (p < 0.0001). Paired Student t test, however, showed significant
      difference between TNC and VUE-art attenuation of kidneys, right adrenal gland,
      paraspinal muscle, and aorta. There was also significant difference between TNC
      and VUE-ven attenuation of left kidney. Percentage of cases which had >10 HU
      difference between VUE and TNC for an individual was calculated which ranged
      between 13% (right kidney) and 42% (right adrenal gland). CONCLUSION: Although
      the correlation between VUE and TNC attenuation values was excellent and mean
      difference between TNC and VUE attenuation values was negligible (ranging between
      -5.94 HU for paraspinal muscles to 6.2 HU in aorta), intra-patient analysis
      showed a considerable number of cases which had >10 HU difference between VUE and
      TNC. VUE-ven generally offered a better approximation of TNC values. Further
      optimization of post-processing algorithms might be necessary before complete
      replacement of TNC with VUE images.

PMID- 27864602
TI  - Beyond bread and beer: whole cell protein extracts from baker's yeast as a bulk
      source for 3D cell culture matrices.
AB  - Here, we present a novel approach to form hydrogels from yeast whole cell
      protein. Countless hydrogels are available for sophisticated research, but their
      fabrication is often difficult to reproduce, with the gels being complicated to
      handle or simply too expensive. The yeast hydrogels presented here are
      polymerized using a four-armed, amine reactive crosslinker and show a high
      chemical and thermal resistance. The free water content was determined by
      measuring swelling ratios for different protein concentrations, and in a freeze
      drying approach, pore sizes of up to 100 MUm in the gel could be created without
      destabilizing the 3D network. Elasticity was proofed to be adjustable with the
      help of atomic force microscopy by merely changing the amount of used protein.
      Furthermore, the material was tested for possible cell culture applications;
      diffusion rates in the network are high enough for sufficient supply of human
      breast cancer cells and adenocarcinomic human alveolar basal epithelial cells
      with nutrition, and cells showed high viabilities when tested for compatibility
      with the material. Furthermore, hydrogels could be functionalized with RGD
      peptide and the optimal concentration for sufficient cell adhesion was determined
      to be 150 MUM. Given that yeast protein is one of the cheapest and easiest
      available protein sources and that hydrogels are extremely easy to handle, the
      developed material has highly promising potential for both sophisticated cell
      culture techniques as well as for larger scale industrial applications.

PMID- 27864601
TI  - Predictors of primary care provider adoption of CT colonography for colorectal
      cancer screening.
AB  - PURPOSE: To examine factors influencing primary care provider (PCP) adoption of
      CT colonography (CTC) for colorectal cancer (CRC) screening. MATERIALS AND
      METHODS: We performed a retrospective cohort study linking electronic health
      record (EHR) data with PCP survey data. Patients were eligible for inclusion if
      they were not up-to-date with CRC screening and if they had CTC insurance
      coverage in the year prior to survey administration. PCPs were included if they
      had at least one eligible patient in their panel and completed the survey (final
      sample N = 95 PCPs; N = 6245 patients). Survey data included perceptions of CRC
      screening by any method, as well as CTC specifically. Multivariate logistic
      regression estimated odds ratios and 95% confidence intervals for PCP and clinic
      predictors of CRC screening by any method and screening with CTC. RESULTS:
      Substantial variation in CTC use was seen among PCPs and clinics (range 0-16% of
      CRC screening). Predictors of higher CTC use were PCP perceptions that CTC is
      effective in reducing CRC mortality, higher number of perceived advantages to
      screening with CTC, and Internal Medicine specialty. Factors not associated with
      CTC use were PCP perceptions of less organizational capacity to meet demand for
      colonoscopy, number of perceived disadvantages to screening with CTC, PCP age and
      gender, and clinic factors. CONCLUSION: Significant variation in PCP adoption of
      CTC exists. PCP perceptions of CTC and specialty practice were related to CTC
      adoption. Strategies to increase PCP adoption of CTC for CRC screening should
      include emphasis on the effectiveness and advantages of CTC.

PMID- 27864603
TI  - Presence of risk factors does not affect outcome in early stage pediatric Hodgkin
      lymphoma treated with ABVD.

PMID- 27864604
TI  - The long-term outcome of reduced-intensity allogeneic stem cell transplantation
      from a matched related or unrelated donor, or haploidentical family donor in
      patients with leukemia: a retrospective analysis of data from the China RIC
      Cooperative Group.
AB  - This study compared 6-year follow-up data from patients undergoing reduced
      intensity conditioning (RIC) transplantation with an HLA-matched related donor
      (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID)
      for leukemia. Four hundred and twenty-seven patients from the China RIC
      Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47
      in the MUD groups. The conditioning regimen involved fludarabine combined with
      anti-lymphocyte globulin and cyclophosphamide. Graft-versus-host disease (GVHD)
      prophylaxis was administered using cyclosporin A (CsA) and mycophenolate mofetil
      (MMF). Four hundred and nineteen patients achieved stable donor chimerism. The
      incidence of stage II-IV acute GVHD in the HID group was 44.3 %, significantly
      higher than that in the MRD (23.6 %) and MUD (19.1 %) groups. The 1-year
      transplantation-related mortality (TRM) rates were 44.3, 17.6, and 21.3,
      respectively. Event-free survival (EFS) at 6 years in the HID group was 36.7 %,
      significantly lower than that of the MRD and MUD groups (59.1 and 66.0 %, P <
      0.001 and P = 0.001, respectively). For advanced leukemia, the relapse rate of
      the HID group was 18.5 %, lower than that of the MRD group (37.5 %, P = 0.05),
      but the EFS at 6 years was 31.7 and 30.4 % (P > 0.05), respectively. RIC
      transplantation with MRD and MUD had similar outcome in leukemia which is better
      than that with HID. RIC transplantation with HID had lower relapsed with higher
      TRM and GVHD rate, particularly in advanced leukemias. RIC transplantation with
      MRD and MUD had similar outcomes in leukemia and they were better than those with
      HID. RIC transplantation with HID had a lower relapse rate but higher TRM and
      GVHD rates, particularly in cases of advanced leukemia.

PMID- 27864605
TI  - Erratum to: BCR-ABL-positive acute myeloid leukemia: About one case treated with
      ponatinib.

PMID- 27864606
TI  - Growth increase of Arabidopsis by forced expression of rice 45S rRNA gene.
AB  - KEY MESSAGE: Forced expression of rice 45S rRNA gene conferred ca. 2-fold
      increase of above-ground growth in transgenic Arabidopsis . This growth increase
      was probably brought by cell proliferation, not by cell enlargement. Recent
      increase in carbon dioxide emissions is causing global climate change. The use of
      plant biomass as alternative energy source is one way to reduce these emissions.
      Therefore, reinforcement of plant biomass production is an urgent key issue to
      overcome both depletion of fossil energies and emission of carbon dioxide. Here,
      we created transgenic Arabidopsis with a 2-fold increase in above-ground growth
      by forced expression of the rice 45S rRNA gene using the maize ubiquitin
      promoter. Although the size of guard cells and ploidy of leaf-cells were similar
      between transgenic and control plants, numbers of stomata and pavement cells were
      much increased in the transgenic leaf. This data suggested that cell number, not
      cell expansion, was responsible for the growth increase, which might be brought
      by the forced expression of exogenous and full-length 45S rRNA gene. The
      expression level of rice 45S rRNA transcripts was very low, possibly triggering
      unknown machinery to enhance cell proliferation. Although microarray analysis
      showed enhanced expression of ethylene-responsive transcription factors, these
      factors might respond to ethylene induced by abiotic/biotic stresses or genomic
      incompatibility, which might be involved in the expression of species-specific
      internal transcribed spacer (ITS) sequences within rice 45S rRNA transcripts.
      Further analysis of the mechanism underlying the growth increase will contribute
      to understanding the regulation of the cell proliferation and the mechanism of
      hybrid vigor.

PMID- 27864608
TI  - Viper Venom Botox: The Molecular Origin and Evolution of the Waglerin Peptides
      Used in Anti-Wrinkle Skin Cream.
AB  - The molecular origin of waglerin peptides has remained enigmatic despite their
      industrial application in skin cream products to paralyse facial muscles and thus
      reduce the incidence of wrinkles. Here we show that these neurotoxic peptides are
      the result of de novo evolution within the prepro region of the C-type
      natriuretic peptide gene in Tropidolaemus venoms, at a site distinct from the
      domain encoding for the natriuretic peptide. It is the same region that yielded
      the azemiopsin peptides from Azemiops feae, indicative of a close relationship of
      this toxin gene between these two genera. The precursor region for the molecular
      evolution is a biodiversity hotspot that has yielded other novel bioactive
      peptides with novel activities. We detail the diversity of components in this and
      other species in order to explore what characteristics enable it to be such a
      biodiscovery treasure trove. The unusual function of Tropidolaemus venoms may
      have been selected for due to evolutionary pressures brought about by a high
      likelihood of prey escape.

PMID- 27864609
TI  - Myocardial Infarction as a Complication of Bronchial Artery Embolization.
AB  - Bronchial artery embolization is now a common treatment for massive pulmonary
      hemoptysis if flexible bronchoscopy at the bedside failed to control the
      bleeding. Complications of this technique range from benign chest pain to
      devastating neurological impairments. We report the case of a 41-year-old man who
      developed an ST elevation myocardial infarction during bronchial artery
      embolization, presumably because of coronary embolism by injected particles. In
      this patient who had no previously known coronary artery disease, we
      retrospectively found a communication between the left bronchial artery and the
      circumflex coronary artery. This fistula was not visible on the initial
      angiographic view and likely opened because of the hemodynamic changes resulting
      from the embolization. This case advocates for careful search for bronchial-to
      coronary arterial fistulas and the need for repeated angiographic views during
      embolization procedures.

PMID- 27864610
TI  - The Monorail Technique to Overcome Difficult Anatomical Course During
      Implantation of Central Venous Port via the Left Internal Jugular Vein.
AB  - PURPOSE: The study aimed to introduce a monorail technique to overcome difficult
      anatomical course via left internal jugular vein in implantable port insertion.
      METHODS: From 2007 to 2016, a total of 9346 patients were referred for
      implantable port insertion in our interventional unit, among which 79 cases were
      requested to insert on the left side. Our monorail technique was applied only
      when the technical challenge of the catheter tip entering the azygos vein instead
      of the superior vena cava occurred (n = 7). The technique consists of puncturing
      at the distal tip of the port catheter with a 21-gauge micropuncture needle and
      advancing a 0.018-in. hair-wire to guide and provide support for pre-assembled
      port. RESULTS: The monorail technique was performed in seven patients and all but
      one case were technically successful, showing a technical success rate of 85.7%.
      There were no immediate or delayed complications. CONCLUSIONS: The monorail
      technique is helpful to overcome the difficult anatomical course via left
      internal jugular vein in implantable port insertion.

PMID- 27864607
TI  - Computed tomography versus invasive coronary angiography: design and methods of
      the pragmatic randomised multicentre DISCHARGE trial.
AB  - OBJECTIVES: More than 3.5 million invasive coronary angiographies (ICA) are
      performed in Europe annually. Approximately 2 million of these invasive
      procedures might be reduced by noninvasive tests because no coronary intervention
      is performed. Computed tomography (CT) is the most accurate noninvasive test for
      detection and exclusion of coronary artery disease (CAD). To investigate the
      comparative effectiveness of CT and ICA, we designed the European pragmatic
      multicentre DISCHARGE trial funded by the 7th Framework Programme of the European
      Union (EC-GA 603266). METHODS: In this trial, patients with a low-to-intermediate
      pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA
      because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA.
      CT and ICA findings guide subsequent management decisions by the local heart
      teams according to current evidence and European guidelines. RESULTS: Major
      adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial
      infarction and stroke as a composite endpoint will be the primary outcome
      measure. Secondary and other outcomes include cost-effectiveness, radiation
      exposure, health-related quality of life (HRQoL), socioeconomic status,
      lifestyle, adverse events related to CT/ICA, and gender differences. CONCLUSIONS:
      The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. KEY
      POINTS: * Coronary artery disease (CAD) is a major cause of morbidity and
      mortality. * Invasive coronary angiography (ICA) is the reference standard for
      detection of CAD. * Noninvasive computed tomography angiography excludes CAD with
      high sensitivity. * CT may effectively reduce the approximately 2 million
      negative ICAs in Europe. * DISCHARGE addresses this hypothesis in patients with
      low-to-intermediate pretest probability for CAD.

PMID- 27864611
TI  - Perioperative Hemodynamic Monitoring of Common Hepatic Artery for Endovascular
      Embolization of a Pancreaticoduodenal Arcade Aneurysm with Celiac Stenosis.
AB  - This report describes perioperative hemodynamic monitoring of the common hepatic
      artery (CHA) during endovascular treatment of a pancreaticoduodenal arcade
      aneurysm, in a patient with celiac artery stenosis caused by the median arcuate
      ligament. Pressure monitoring was performed as a safety measure against critical
      complications such as liver ischemia. As the aneurysm was located in the anterior
      pancreaticoduodenal artery (APDA) and the posterior pancreaticoduodenal artery
      (PPDA) was small in caliber, the patient was considered to be at a high risk of
      liver ischemia. No significant change in pressure was observed in the CHA on
      balloon occlusion test in the APDA. Immediately after embolization, the PPDA
      enlarged and the pressure in the CHA was well maintained. Pressure monitoring
      appears to improve patient safety during endovascular treatment of visceral
      aneurysms.

PMID- 27864612
TI  - Secretory products from epicardial adipose tissue from patients with type 2
      diabetes impair mitochondrial beta-oxidation in cardiomyocytes via activation of
      the cardiac renin-angiotensin system and induction of miR-208a.
AB  - Secretory products from epicardial adipose tissue (EAT) from patients with type 2
      diabetes (T2D) impair cardiomyocyte function. These changes associate with
      alterations in miRNA expression, including the induction of miR-208a. Recent
      studies suggest that activation of the cardiac-specific renin-angiotensin system
      (RAS) may affect cardiac energy metabolism via induction of miR-208a. This study
      investigated whether cardiomyocyte dysfunction induced by conditioned media (CM)
      from EAT-T2D involves activation of the RAS/miR-208a pathway. Therefore, primary
      adult rat cardiomyocytes were incubated with CM generated from EAT biopsies from
      patients with T2D and without T2D (ND). Exposing cardiomyocytes to CM-EAT-T2D
      reduced sarcomere shortening and increased miR-208a expression versus cells
      exposed to CM-EAT-ND or control medium. The angiotensin II receptor type 1
      (AGTR1) antagonist losartan reversed these effects. Accordingly, incubation with
      angiotensin II (Ang II) reduced sarcomere shortening, and lowered palmitate
      induced mitochondrial respiration and carnitine palmitoyltransferase 1c (CPT1c)
      expression in cardiomyocytes. Locked-nucleic-acid-mediated inhibition of miR-208a
      function reversed the detrimental effects induced by Ang II. Interestingly, Ang
      II levels in CM-EAT-T2D were increased by 2.6-fold after culture with
      cardiomyocytes. The paracrine activation of the cardiac-specific RAS by CM-EAT
      T2D was corroborated by increases in the expression of AGTR1 and renin, as well
      as a reduction in angiotensin-converting enzyme 2 levels. Collectively, these
      data show that secretory products from EAT-T2D impair cardiomyocyte contractile
      function and mitochondrial beta-oxidation via activation of the cardiac-specific
      RAS system and induction of miR-208a, and suggest that alterations in the
      secretory profile of EAT may contribute to the development of diabetes-related
      heart disease.

PMID- 27864614
TI  - Paediatric cardiopulmonary bypass surgery: the challenges of heterogeneity and
      identifying a meaningful endpoint for clinical trials.

PMID- 27864613
TI  - Oncolysate-loaded Escherichia coli bacterial ghosts enhance the stimulatory
      capacity of human dendritic cells.
AB  - The natural adjuvant properties of bacterial ghosts (BGs) lie within the presence
      of intact pathogen-associated molecular patterns on their surface. BGs can
      improve the direct delivery, natural processing and presentation of target
      antigens within dendritic cells (DCs). Moreover, sensitization of human DCs by
      cancer cell lysate (oncolysate)-loaded BGs in the presence of IFN-alpha and GM
      CSF enhanced DC maturation as indicated by an increased expression of maturation
      markers and co-stimulatory molecules, higher production of IL-12p70 and
      stimulation of significantly increased proliferation of both autologous CD4+ and
      CD8+ T cells compared to DCs matured in the presence of purified
      lipopolysaccharide. The induced T cells efficiently recognized oncolysate-derived
      tumor-associated antigens expressed by cancer cells used for the production of
      oncolysate. Our optimized one-step simultaneous antigen delivery and DC
      maturation-inducing method emerges as a promising tool for the development and
      implementation of next-generation cellular cancer immunotherapies.

PMID- 27864615
TI  - The effects of active mobilisation and rehabilitation in ICU on mortality and
      function: a systematic review.
AB  - PURPOSE: Early active mobilisation and rehabilitation in the intensive care unit
      (ICU) is being used to prevent the long-term functional consequences of critical
      illness. This review aimed to determine the effect of active mobilisation and
      rehabilitation in the ICU on mortality, function, mobility, muscle strength,
      quality of life, days alive and out of hospital to 180 days, ICU and hospital
      lengths of stay, duration of mechanical ventilation and discharge destination,
      linking outcomes with the World Health Organization International Classification
      of Function Framework. METHODS: A PRISMA checklist-guided systematic review and
      meta-analysis of randomised and controlled clinical trials. RESULTS: Fourteen
      studies of varying quality including a total of 1753 patients were reviewed.
      Active mobilisation and rehabilitation had no impact on short- or long-term
      mortality (p > 0.05). Meta-analysis showed that active mobilisation and
      rehabilitation led to greater muscle strength (body function) at ICU discharge as
      measured using the Medical Research Council Sum Score (mean difference 8.62
      points, 95% confidence interval (CI) 1.39-15.86), greater probability of walking
      without assistance (activity limitation) at hospital discharge (odds ratio 2.13,
      95% CI 1.19-3.83), and more days alive and out of hospital to day 180
      (participation restriction) (mean difference 9.69, 95% CI 1.7-17.66). There were
      no consistent effects on function, quality of life, ICU or hospital length of
      stay, duration of mechanical ventilation or discharge destination. CONCLUSION:
      Active mobilisation and rehabilitation in the ICU has no impact on short- and
      long-term mortality, but may improve mobility status, muscle strength and days
      alive and out of hospital to 180 days. REGISTRATION OF PROTOCOL NUMBER:
      CRD42015029836.

PMID- 27864616
TI  - Randomized Clinical Trial Comparing Cyanoacrylate Glue Versus Suture Fixation in
      Lichtenstein Hernia Repair: 7-Year Outcome Analysis.
AB  - BACKGROUND: Lichtenstein hernioplasty has relatively low recurrence rate, but
      chronic inguinal pain may cause harm to the patient. The aim of our study was to
      compare long-term results of cyanoacrylate glue versus absorbable sutures for
      mesh fixation in Lichtenstein hernioplasty. METHODS: Lichtenstein hernioplasty (n
      = 302) was performed under local anesthesia in three hospitals. The patients were
      randomized to receive either 1 ml of butyl-2-cyanoacrylate tissue glue
      (Glubran(r); 151 hernias) or absorbable polyglycolic acid sutures (Dexon(r); 151
      hernias) for mesh fixation (Optilene(r) mesh). Short-term results were published
      previously. Chronic groin pain, foreign body sensation, use of analgesics,
      recurrence and re-operations were analyzed 7 years after surgery. RESULTS: We
      reached 236 patients (78%) to present study. In the glue group (n = 115), there
      were five (4.3%) and in the suture group (n = 121) three (2.5%) recurrent hernias
      (p = 0.491). The prevalence of chronic pain (NRS >= 3) in the patients without re
      operations was similar in two groups: 15/118 (13%) and 13/111 (12%), respectively
      (p = 0.843). There were no significant differences in the foreign body sensation
      (8/14, p = 0.267) or in the need of analgesics (2/2, p = 1.00) between the two
      study groups. CONCLUSION: Both cyanoacrylate glue and mesh fixation with
      absorbable sutures were equal in terms of chronic pain and rate of recurrences in
      Lichtenstein hernioplasty after 7-year follow-up. TRIAL REGISTRATION NUMBER:
      NCT00659542.

PMID- 27864618
TI  - Hypertension is the primary component of metabolic syndrome associated with
      pathologic features of kidney cancer: methodological issues.

PMID- 27864617
TI  - Diagnostic Accuracy of Abdominal Ultrasound for Diagnosis of Acute Appendicitis:
      Systematic Review and Meta-analysis.
AB  - BACKGROUND: To determine the diagnostic accuracy of abdominal ultrasound (US) for
      the diagnosis of acute appendicitis (AA), in terms of sensitivity, specificity
      and post-test probabilities for positive and negative result. METHODS: A
      systematic search of MEDLINE, Embase, The Cochrane library and Science Citation
      Index Expanded from January 1994 to October 2014 was performed. Two authors
      independently evaluated studies for inclusion, extracted data and performed
      analyses. The reference standard for evaluation of final diagnosis was
      pathohistological report on tissue obtained at appendectomy. Summary sensitivity,
      specificity and post-test probability of AA after positive and negative result of
      US with corresponding 95% confidence intervals (CI) were calculated. RESULTS: Out
      of 3306 references identified through electronic searches, 17 reports met the
      inclusion criteria, with 2841 included participants. The summary sensitivity and
      specificity of US for diagnosis of AA were 69% (95% CI 59-78%) and 81% (95% CI 73
      88%), respectively. At the median pretest probability of AA of 76.4%, the post
      test probability for a positive and negative result of US was 92% (95% CI 88-95%)
      and 55% (95% CI 46-63%), respectively. CONCLUSIONS: Abdominal ultrasound does not
      seem to have a role in the diagnostic pathway for diagnosis of AA in suspected
      patients. The summary sensitivity and specificity of US do not exceed that of
      physical examination. Patients that require additional diagnostic workup should
      be referred to more sensitive and specific diagnostic procedures, such as
      computed tomography.

PMID- 27864619
TI  - Bicentric prospective evaluation of corporoplasty with porcine small intestinal
      submucosa (SIS) in patients with severe Peyronie's disease.
AB  - INTRODUCTION: Advanced Peyronie's disease (PD) with severe penile deviation
      demands grafting procedures following plaque incision or partial plaque excision
      in order to avoid penile shortening and to improve quality of life of affected
      patients. Small intestinal submucosa (SIS) is an established xenograft. The
      objective of the present study was to validate external results in a bicentric
      prospective manner. METHODS: Patient selection criteria, surgical technique and
      standards for pre- and postoperative care were defined. Consecutively, patients
      with severe penile deviation in stable disease and sufficient erectile function
      were included between 2007 and 2015. After plaque incision, grafting was
      performed using SIS in a standardized manner. The postoperative evaluation using
      a non-validated questionnaire included complications, correction of curvature,
      pre- and postoperative erectile function, change in penile length and general
      satisfaction with the procedure. RESULTS: Forty-three patients underwent surgery
      between 2007 and 2015. The mean degree of preoperative curvature was 73.8 degrees
      (range 60-90 degrees ). No intraoperative or major postoperative complications
      were reported. After a mean follow-up of 33.0 months (range 10-59), complete
      straightening of the penis was achieved in 74.4%. 88.4% of all patients were able
      to achieve satisfying sexual intercourse (67.4% unaided, 21.0% with assistance).
      The IIEF-5 score was improved in 69.8% (mean improvement 4.0 points). Overall
      86.0% were satisfied with the surgical treatment. CONCLUSION: Corporoplasty with
      SIS in patients with PD and severe penile curvature is a safe approach and shows
      good long-term results. A thorough patient selection and a standardized pre-,
      intra- and postoperative procedure are decisive for a satisfying outcome.

PMID- 27864620
TI  - Long-term outcomes of transobturator tension-free vaginal tapes as secondary
      continence procedures.
AB  - PURPOSE: To assess the long-term patient-reported outcomes following TO-TVT as a
      secondary continence procedure in women with recurrent stress urinary
      incontinence (R-SUI). METHODS: A secondary analysis of the 9-year follow-up of
      the E-TOT study was performed: 341 women with predominant SUI symptoms were
      randomised to undergo either Inside-out or Outside-in TO-TVT between April 2005
      and April 2007. Forty-six women had R-SUI following previously failed continence
      surgery at time of randomisation and are the basis of this analysis as a one
      single cohort. Primary outcome was the patient-reported success rate defined as
      very/much improved on Patient's Global Impression of Improvement (PGI-I).
      Secondary outcomes included late adverse events and impact on women's quality of
      life and sexual function. Statistical analysis was performed using SPSS version
      23. RESULTS: Sixty-three per cent completed the 9-year follow-up. The success
      based on the PGI-I was 62.1% with no significant difference between groups (OR
      5.33; 95% CI 1.03, 27.76; p = 0.094). Clinically significant improvement in QoL
      was found in 84.2%. Adverse events included vaginal erosions (n = 3) and groin
      pain (n = 2). The small sample size is a limitation in this study; nevertheless,
      this is one of the largest cohorts reported for women with R-SUI and the first to
      report the long-term outcomes of TO-TVT as a secondary continence procedure.
      CONCLUSIONS: TO-TVT operations are associated with good patient-reported success
      rates (62%) in women with previous failed continence surgery with up to 9-years
      follow-up. There is a non-significant trend towards better outcomes with the
      inside-out TO-TVT.

PMID- 27864621
TI  - Factors associated with the presence of postoperative headache in elective
      surgery patients: a prospective single center cohort study.
AB  - PURPOSE: Headache is an important cause of minor postoperative morbidity. In this
      study we evaluated the association of anesthesia and surgery with the occurrence
      of postoperative headache in elective surgery patients. METHODS: After obtaining
      ethical approval, 446 patients were enrolled in this prospective, single-centre
      cohort study. Participants were interviewed preoperatively, and for five days
      postoperatively, regarding the appearance of headache, while demographics,
      lifestyle, type of anesthesia and surgery, the anesthetic drugs administered and
      intraoperative adverse effects were recorded. Multiple logistic regression
      analysis was conducted in order to identify independent factors associated with
      postoperative headache, both in the total sample and in patients without previous
      history of headache. RESULTS: The observed overall frequency of postoperative
      headache was 28.3% (N = 126) in the total sample. In patients with previous
      history of headache, the frequency of postoperative headache was 41% (N = 89),
      while in those with no history the frequency of postoperative headache was 16.2%
      (N = 37). Female gender [p = 0.024; odds ratio (OR) = 2.1], sevoflurane
      administration (p < 0.001; OR = 3.66), intraoperative hypotension (p = 0.008; OR
      = 2.12) and smoking (p = 0.006; OR = 1.74) were independently associated with
      postoperative headache. In patients without previous history, female gender (p =
      0.005; OR = 4.77), sevoflurane administration (p = 0.001; OR = 6.9),
      intraoperative hypotension (p = 0.006; OR = 6.7) and caffeine consumption (p =
      0.041; OR = 5.28) presented greater likelihood for postoperative headache, while
      smoking revealed no association. CONCLUSION: Female gender, sevoflurane, smoking
      and intraoperative hypotension were documented as independent risk factors for
      postoperative headache. In patients with no previous history of headache,
      caffeine consumption was an additional independent factor for postoperative
      headache, while smoking revealed no association.

PMID- 27864622
TI  - How obesity impacts outcomes of infectious diseases.
AB  - Obesity is associated with co-morbidities and increased risk of acquiring
      infections with worse outcomes. Paradoxically, a few studies indicate that
      obesity may have a decreased mortality in hospitalized patients with pneumonia.
      The objective of this study was to determine the impact of body mass index (BMI)
      on short-term all-cause mortality and clinical outcomes among hospitalized adults
      with pneumonia, urinary tract infections, skin and soft tissue infections, and
      bacteremia. The study cohort included 1437 consecutive patients who were admitted
      with infectious disease including pneumonia (717), urinary tract infection (506),
      bacteremia (69), and skin and soft tissue infections (145), and hospitalized in
      internal medical departments, during 2013-2015. BMI was categorized as
      underweight (<=20 kg/m2), normal (20-25 kg/m2), overweight (25.1-29.9 kg/m2), and
      obese (>=30 kg/m2). Clinical outcomes of 30- and 90-day all-cause mortality
      rates, length of hospital stay, and transfer to the intensive care unit (ICU)
      were compared among groups, sorted according to BMI and different infectious
      diseases. Obesity was associated with decreased 30-day mortality in patients with
      pneumonia [odds ratio (OR) = 0.26, 95 % confidence interval (CI) 0.06-1.01; p =
      0.052]. On the contrary, increased 30-day mortality was observed in the
      underweight patients (OR = 2.89, 95 % CI 1.1-7.6; p = 0.03). Similar impacts were
      not found for urinary tract infections, skin and soft tissue infections, or
      bloodstream infections. Furthermore, obesity had no effect on 90-day mortality,
      length of hospital stay, or transfer to the ICU in all kinds of infectious
      diseases. Obesity is associated with reduced short-term mortality among
      hospitalized patients with pneumonia. Whether gut microbiota in obese individuals
      plays a role in this protective effect remains to be investigated by further
      studies.

PMID- 27864623
TI  - Simplified HCC-ART score for highly sensitive detection of small-sized and early
      stage hepatocellular carcinoma in the widely used Okuda, CLIP, and BCLC staging
      systems.
AB  - BACKGROUND: Small-sized HCC can be effectively cured by surgery with good
      clinical outcomes. A highly sensitive HCC alpha-fetoprotein routine test (HCC
      ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in
      the British Journal of Cancer. Here, we verified and studied the applicability of
      the HCC-ART to the detection of early-stage HCC. METHODS: 341 cirrhotic patients
      and 318 HCC patients were included in this study. For each, the HCC-ART score was
      calculated, and then the sensitivity, specificity, and results of an ROC curve
      analysis were compared between the HCC-ART and AFP when these biomarkers were
      used to detect small-sized HCC. RESULTS: Different HCC-ART cutoffs were set for
      the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70%
      sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82%
      sensitivity, 100% specificity) were found to have high predictive power when
      attempting to separate cirrhotic patients from those with small-sized HCC. The
      simplified HCC-ART score was superior to AFP for determining stages according to
      the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC,
      84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99%
      specificity) staging systems. The simplified HCC-ART score was more strongly
      correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r
      = 0.8). CONCLUSION: The HCC-ART is superior to AFP for diagnosing early-stage
      HCC. Due to its advantages of minimal variability and a wide continuous scale for
      assessing HCC severity, the simplified HCC-ART has the potential to be more
      widely used than the original HCC-ART.

PMID- 27864624
TI  - Sentinel lymph node biopsy using indocyanine green fluorescence in early-stage
      breast cancer: a meta-analysis.
AB  - Sentinel lymph node (SLN) biopsy using indocyanine green (ICG) fluorescence is
      safe and has a high detection rate for SLNs. However, the results of this novel
      technique are heterogeneous. The objective of this meta-analysis was to evaluate
      the diagnostic performance of the ICG fluorescence method compared with the
      standard radioisotope (RI) method. All eligible studies were identified from 2005
      through 2015. A proportion meta-analysis was performed using a fixed effects
      and/or random effects model based on the study heterogeneity. A total of 12
      studies met the inclusion criteria and included 1736 women. There was no
      significant difference between ICG fluorescence and RI for SLN detection using
      either the fixed effects model [odds ratio (OR) 1.29, 95% confidence interval
      (CI) 0.87-1.90] or the random effects model (OR 1.32, 95% CI 0.54-3.18). There
      were seven studies reporting the detection rate for tumor-positive SLN. The ICG
      fluorescence method was significantly better than the RI method in the fixed
      effects model (OR 1.87, 95% CI 1.00-3.49) for staging axilla. However, there was
      no difference in the random effects model (OR 1.90, 95% CI 0.74-4.86). There was
      study outcome heterogeneity for the detection of SLN but not for tumor-positive
      SLN. There was no publication bias observed in the studies included. The ICG
      fluorescence method has valid diagnostic performance for SLN detection and shows
      a trend toward better axilla staging compared with the RI method. ICG
      fluorescence is a useful alternative to RI for SLN biopsy.

PMID- 27864625
TI  - The Impact of Comorbidities, Depression, and Substance Use Problems on Quality of
      Life Among Older Adults Living With HIV.
AB  - Older adults living with HIV (OALWH) comprise a growing population with a range
      of complex and interconnecting medical and psychosocial needs. Based on the
      biopsychosocial model with its emphasis on a holistic approach to various aspects
      of people's lives, the current study explored associations between physical
      health, psychological health, substance use, and overall quality of life. Drawing
      on data from 114 substance-using OALWH (aged 50 or older), we employed linear
      regression to show associations between the number of current comorbid health
      conditions on quality of life, over and above depression, substance use problems,
      and demographic characteristics (age, race/ethnicity, gender, sexual orientation,
      education, and relationship status). In both bivariate and multivariable
      contexts, the number of comorbid conditions was associated with reduced quality
      of life. Depression and substance use were also negatively associated with
      quality of life. These findings indicate that clinical and supportive care for
      OALWH, particularly when related to mental health and substance use, should also
      include an integrated focus on the comparatively high number of current comorbid
      conditions that often accompany, and potentially complicate, HIV treatment and
      quality of life.

PMID- 27864626
TI  - Can Policy Interventions Affect HIV-Related Behaviors? A Systematic Review of the
      Evidence from Low- and Middle-Income Countries.
AB  - In their response to HIV, many countries have adopted and enacted policies to
      reduce transmission and increase HIV-related service use. Theoretically, policy
      level interventions for HIV prevention have the potential to improve health
      behavior outcomes. These policy interventions vary in their scale, from
      relatively minor changes in clinical policy to major national legal initiatives.
      Assessing the effectiveness of HIV policy interventions is a challenging
      undertaking. While many policies exist and guide HIV programmes, relatively few
      have specifically been evaluated for their effects on reducing HIV risk taking or
      increasing HIV health-seeking behaviors. Thus, questions on the effectiveness of
      policy interventions to prevent HIV and change HIV-related risk behaviors remain
      largely unanswered. To address this current gap in the literature, we
      systematically reviewed the existing evidence on the effect of HIV policy
      interventions on changing HIV-related behaviors in low-and middle-income
      countries.

PMID- 27864627
TI  - Participation in treatment decision-making among Chinese-Australian women with
      breast cancer.
AB  - PURPOSE: Using Confucian philosophy as a conceptual framework, this article
      examines the extent to which cultural values and language affect the
      participation preferences and experiences of the breast cancer treatment decision
      making (TDM) process among Chinese women with breast cancer in Australia.
      METHODS: Three focus groups were conducted with 23 Chinese-Australian women
      diagnosed with breast cancer in their native language (Mandarin and Cantonese).
      Each interview was translated and transcribed. Content analysis was used to
      uncover the major themes. FINDINGS: Four typologies emerged: the patient as an
      active decision maker, the patient as a passive decision maker, the patient as a
      reluctant decision maker and the patient as a reluctant passive decision maker.
      Language barriers, cultural expectation of doctor's role and family role in
      Chinese culture appear as influential factors in TDM process among this group of
      women. CONCLUSIONS: Intervention to improve doctors' cultural sensitivities in
      order to help them assess women's role preferences in TDM and the ability of
      doctors to communicate in a culturally appropriate manner, may improve the
      process of breast cancer TDM among women from Chinese background.

PMID- 27864629
TI  - Cytokeratin AE1/AE3 immunostaining and 3D-histology: improvement of diagnosis in
      desmoplastic squamous cell carcinoma of the skin.
AB  - Desmoplastic squamous cell carcinoma (DSCC) as a rare subtype of cutaneous SCC
      has specific histological features, characterized by columns, bands, and strands
      of squamoid cells infiltrating a dense collagenous stroma. To decrease the high
      rates of local recurrence in DSSC, improvement of diagnostic methods is highly
      demanded. Objective was to evaluate whether immunohistochemistry (IHC) is suited
      to increase diagnostic accuracy. A total number of 18 patients were included in
      this study. After recutting of the original paraffin blocks, parallel staining of
      serial sections with conventionally H&E and cytokeratin AE1/AE3
      immunohistochemical staining was performed. Results were evaluated by an
      experienced dermatohistopathologist. In 55.6% (n = 10), the margins of 3D
      histology still showed no evidence of neoplastic lesions in both stainings. In
      contrast, we found neoplastic lesions in 5 of 18 cases (27.8%) with cytokeratin
      AE1/AE3 staining, while H&E-staining remained negative. In addition, neoplastic
      lesions were found in both, H&E as well as cytokeratin AE1/AE3 staining in three
      cases (16.7%). The data presented show improvement of diagnosis in 27.8% of cases
      using IHC and 3D-histology. This method is suitable to improve the diagnosis of
      DSCC.

PMID- 27864628
TI  - Provider perspectives on patient-provider communication for adjuvant endocrine
      therapy symptom management.
AB  - PURPOSE: Providers' communication skills play a key role in encouraging breast
      cancer survivors to report symptoms and adhere to long-term treatments such as
      adjuvant endocrine therapy (AET). The purpose of this study was to examine
      provider perspectives on patient-provider communication regarding AET symptom
      management and to explore whether provider perspectives vary across the multi
      disciplinary team of providers involved in survivorship care. METHODS: We
      conducted three one-hour focus groups with a multi-disciplinary group of health
      care providers including oncology specialists, primary care physicians, and non
      physician providers experienced in caring for breast cancer survivors undergoing
      AET (n = 13). Themes were organized using Epstein and Street's (2007) Framework
      for Patient-Centered Communication in Cancer Care. RESULTS: The findings of this
      study suggest providers' communication behaviors including managing survivors'
      uncertainty, responding to survivors' emotions, exchanging information, and
      enabling self-management influences the quality of patient-provider communication
      about AET symptoms. Additionally, lack of systematic symptom assessment tools for
      AET requires providers to use discretion in determining which symptoms to discuss
      with survivors resulting in approaches that vary based on providers' discipline.
      CONCLUSION: There may be AET-specific provider communication skills and behaviors
      that promote effective patient-provider communication but additional research is
      needed to identify practices and policies that encourage these skills and
      behaviors among the many providers involved in survivorship care. Efforts are
      also needed to coordinate AET symptom assessment across providers, clarify
      providers' roles in symptom assessment, and determine best practices for AET
      symptom communication.

PMID- 27864630
TI  - The interlaminar glia: from serendipity to hypothesis.
AB  - An account of work performed at the UNA laboratories since 1992 on the detection
      and description of interlaminar glial processes, is presented. The incidental
      observation (serendipity) of longer than expected glial processes in the
      superficial layers of the cerebral cortex in hemiparkinsonian Cebus apella
      monkeys, was expanded afterwards to cover the largest possible sampling of
      representatives of mammalian orders and species, as well as in experimental and
      pathological conditions, in human and non-human primates. The term interlaminar
      was coined to differentiate these processes from the classical astroglial
      stellate, intralaminar ones. Such account grew to the point of inspiring, on
      speculative grounds, possible roles in the organization of the cerebral cortex.
      Interlaminar glial processes represent an essentially primate characteristic,
      affected by neuropathological conditions such as DS and AD and experimental
      procedures affecting normal sensory input, suggesting thalamic involvement in
      their normal expression. Their ontogenetic development, phylogenetic evolution
      and aging changes are described.

PMID- 27864631
TI  - Factors affecting efficacy of packed red blood cell transfusion in neonates.
AB  - : The degree of increase in haematocrit and equilibration time following packed
      red blood cell (PRBC) transfusion in neonates is not well studied. We evaluated
      change in haematocrit 15 min, 6 h and 24 h after PRBC transfusion in neonates and
      factors predicting this change. Among neonates receiving PRBC transfusion, we
      recorded pre-transfusion haematocrit and a priori identified putative variables
      affecting change in haematocrit following transfusion. The factors affecting
      change in haematocrit were analyzed by multiple linear regression analysis.
      Eighty-one neonates received 119 PRBC transfusions (mean volume 16 +/- 4 mL/kg).
      Haematocrit increased from 26 +/- 5 to 41 +/- 5% at 15 min after PRBC transfusion
      (p = 0.001) and remained stable till 6 h (41 +/- 5%, p = 0.11). It decreased to
      40 +/- 5%, at 24 h post transfusion (p < 0.001). On linear regression analysis,
      baseline haematocrit of the baby, donor blood haematocrit and volume of PRBC
      transfusion were independent determinants of increase in haematocrit. CONCLUSION:
      After 16 mL/kg PRBC transfusion in neonates, haematocrit increased by 15% at 15
      min post transfusion. The equilibration in haematocrit values was achieved by 15
      min after transfusion. Baseline haematocrit of neonate, donor blood haematocrit
      and transfusion volume independently determine the rise in haematocrit. What is
      Known: * Rise in haematocrit following PRBC transfusion in neonates has been
      studied in a small number of stable infants. * Determinants of efficacy of PRBC
      transfusion have not been well studied in newborns. What is New: * Each
      milliliter/kilogramme of PRBC transfusion increases the neonate's haematocrit by
      approximately 1%. * Baseline haematocrit, donor blood haematocrit and transfusion
      volume per kilogramme body weight independently determine the rise in
      haematocrit.

PMID- 27864633
TI  - Biological characterization of highly pathogenic avian influenza H5N1 viruses
      that infected humans in Egypt in 2014-2015.
AB  - Highly pathogenic avian influenza (HPAI) H5N1 influenza viruses emerged as a
      human pathogen in 1997 with expected potential to undergo sustained human-to
      human transmission and pandemic viral spread. HPAI H5N1 is endemic in Egyptian
      poultry and has caused sporadic human infection. The first outbreak in early 2006
      was caused by clade 2.2 viruses that rapidly evolved genetically and
      antigenically. A sharp increase in the number of human cases was reported in
      Egypt in the 2014/2015 season. In this study, we analyzed and characterized three
      isolates of HPAI H5N1 viruses isolated from infected humans in Egypt in
      2014/2015. Phylogenetic analysis demonstrated that the nucleotide sequences of
      eight segments of the three isolates were clustered with those of members of
      clade 2.2.1.2. We also found that the human isolates from 2014/2015 had a slight,
      non-significant difference in their affinity for human-like sialic acid
      receptors. In contrast, they showed significant differences in their replication
      kinetics in MDCK, MDCK-SIAT, and A549 cells as well as in embryonated chicken
      eggs. An antiviral bioassay study revealed that all of the isolates were
      susceptible to amantadine. Therefore, further investigation and monitoring is
      required to correlate the genetic and/or antigenic changes of the emerging HPAI
      H5N1 viruses with possible alteration in their characteristics and their
      potential to become a further threat to public health.

PMID- 27864634
TI  - Reactions of aquacobalamin and cob(II)alamin with chlorite and chlorine dioxide.
AB  - Reactions of aquacobalamin (H2O-Cbl(III)) and its one-electron reduced form
      (cob(II)alamin, Cbl(II)) with chlorite (ClO2-) and chlorine dioxide (ClO 2* )
      were studied by conventional and stopped-flow UV-Vis spectroscopies and matrix
      assisted laser desorption/ionization-mass spectrometry (MALDI-MS). ClO2- does not
      react with H2O-Cbl(III), but oxidizes Cbl(II) to H2O-Cbl(III) as a major product
      and corrin-modified species as minor products. The proposed mechanism of chlorite
      reduction involves formation of OCl- that modifies the corrin ring during the
      course of reaction with Cbl(II). H2O-Cbl(III) undergoes relatively slow
      destruction by ClO 2* via transient formation of oxygenated species, whereas
      reaction between Cbl(II) and ClO 2* proceeds extremely rapidly and leads to the
      oxidation of the Co(II)-center.

PMID- 27864636
TI  - Do early postoperative CT findings following type A aortic dissection repair
      predict early clinical outcome?
AB  - PURPOSE: The purposes of this study are to determine the prevalence of specific
      postoperative CT findings following Stanford type A aortic dissection repair in
      the early postoperative period and to determine if these postoperative findings
      are predictive of adverse clinical outcome. METHODS: Patients who underwent type
      A dissection repair between January 2012 and December 2014 were identified from
      our institutional cardiac surgery database. Postoperative CT exams within 1 month
      of surgery were retrospectively reviewed to determine sizes and attenuation of
      mediastinal, pericardial, and pleural fluid, and the presence or absence of
      pneumomediastinum, pneumothorax, or lung consolidation. Poor early clinical
      outcome was defined as length of stay (LOS) > 14 days. Student's t test and chi
      square test were used to determine the relationship between postoperative CT
      features and early clinical outcome. RESULTS: Thirty-nine patients (24 M, 15 F,
      mean age 58.5 +/- 13.7 years) underwent type A dissection repair and mean LOS was
      17.3 +/- 21.2 days. A subset of 19 patients underwent postoperative CTs within 30
      days of surgery, and there was no significant relationship between LOS and sizes
      and attenuation of mediastinal, pericardial, and pleural fluid, and the presence
      or absence of pneumomediastinum, pneumothorax, or lung consolidation.
      CONCLUSIONS: CT features such as mediastinal, pericardial, and pleural fluid were
      ubiquitous in the early postoperative period. There was no consistent CT feature
      or threshold that could reliably differentiate between "normal postoperative
      findings" and early postoperative complications.

PMID- 27864635
TI  - Soluble CD200 Correlates With Interleukin-6 Levels in Sera of COPD Patients:
      Potential Implication of the CD200/CD200R Axis in the Disease Course.
AB  - BACKGROUND: COPD represents a multifactorial lung disorder with high morbidity
      and mortality. Despite intensive research concerning the underlying disease
      mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing
      the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is
      crucially implicated in the maintenance of pulmonary immune homeostasis, we
      hypothesized that it might be involved in controlling the onset of COPD. METHODS:
      To address this, we analyzed the serum samples from COPD patients and normal
      controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical
      parameters. In addition, basic studies were conducted in CD200-deficient and wild
      type mice in which COPD-like inflammation was induced with elastase/LPS followed
      by lung and serum component analysis. RESULTS: We observed a positive correlation
      between serum sCD200 and IL-6 levels as well as a trend toward a negative
      correlation of sCD200 with vitamin D3 in COPD patients. Further investigations in
      mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice,
      the early onset of COPD-like lung inflammation was similar in CD200-deficient and
      wild-type animals in terms of immune cell infiltration, emphysematous changes,
      and mucus overproduction. CONCLUSIONS: While our murine studies suggest that the
      co-inhibitory molecule CD200 does not appear to play a prominent role in the
      early onset of COPD-like features, correlation of sCD200 serum levels with COPD
      related parameters in humans with established disease revealed that the
      CD200/CD200R axis may be mechanistically linked to the disease course in COPD
      patients.

PMID- 27864637
TI  - Separate and combined effects of exposure to heat stress and mental fatigue on
      endurance exercise capacity in the heat.
AB  - PURPOSE: This study investigated the effects of exposure to pre-exercise heat
      stress and mental fatigue on endurance exercise capacity in a hot environment.
      METHODS: Eight volunteers completed four cycle exercise trials at 80% maximum
      oxygen uptake until exhaustion in an environmental chamber maintained at 30 
      degrees C and 50% relative humidity. The four trials required them to complete a
      90 min pre-exercise routine of either a seated rest (CON), a prolonged demanding
      cognitive task to induce mental fatigue (MF), warm water immersion at 40  degrees
      C during the last 30 min to induce increasing core temperature (WI), or a
      prolonged demanding cognitive task and warm water immersion at 40  degrees C
      during the last 30 min (MF + WI). RESULTS: Core temperature when starting
      exercise was higher following warm water immersion (~38  degrees C; WI and MF +
      WI) than with no water immersion (~36.8  degrees C; CON and MF, P < 0.001). Self
      reported mental fatigue when commencing exercise was higher following cognitive
      task (MF and MF + WI) than with no cognitive task (CON and WI; P < 0.05).
      Exercise time to exhaustion was reduced by warm water immersion (P < 0.001) and
      cognitive task (P < 0.05). Compared with CON (18 +/- 7 min), exercise duration
      reduced 0.8, 26.6 and 46.3% in MF (17 +/- 7 min), WI (12 +/- 5 min) and MF + WI
      (9 +/- 3 min), respectively. CONCLUSIONS: This study demonstrates that endurance
      exercise capacity in a hot environment is impaired by either exposure to pre
      exercise heat stress or mental fatigue, and this response is synergistically
      increased during combined exposure to them.

PMID- 27864638
TI  - Effects of caffeine on neuromuscular fatigue and performance during high
      intensity cycling exercise in moderate hypoxia.
AB  - PURPOSE: To investigate the effects of caffeine on performance, neuromuscular
      fatigue and perception of effort during high-intensity cycling exercise in
      moderate hypoxia. METHODS: Seven adult male participants firstly underwent an
      incremental exercise test on a cycle ergometer in conditions of acute normobaric
      hypoxia (fraction inspired oxygen = 0.15) to establish peak power output (PPO).
      In the following two visits, they performed a time to exhaustion test (78 +/- 3%
      PPO) in the same hypoxic conditions after caffeine ingestion (4 mg kg-1) and one
      after placebo ingestion in a double-blind, randomized, counterbalanced cross-over
      design. RESULTS: Caffeine significantly improved time to exhaustion by 12%. A
      significant decrease in subjective fatigue was found after caffeine consumption.
      Perception of effort and surface electromyographic signal amplitude of the vastus
      lateralis were lower and heart rate was higher in the caffeine condition when
      compared to placebo. However, caffeine did not reduce the peripheral and central
      fatigue induced by high-intensity cycling exercise in moderate hypoxia.
      CONCLUSION: The caffeine-induced improvement in time to exhaustion during high
      intensity cycling exercise in moderate hypoxia seems to be mediated by a
      reduction in perception of effort, which occurs despite no reduction in
      neuromuscular fatigue.

PMID- 27864639
TI  - Molecular phylogeny of the cosmopolitan aquatic plant genus Limosella
      (Scrophulariaceae) with a particular focus on the origin of the Australasian L.
      curdieana.
AB  - Limosella is a small aquatic genus of Scrophulariaceae of twelve species, of
      which one is distributed in northern circumpolar regions, two in southern
      circumpolar regions, two in the Americas, one endemic to Australia, and six in
      tropical or southern Africa or both. The Australasian L. curdieana has always
      been considered distinct but its close phylogenetic relationships have never been
      inferred. Here, we investigated the following alternative phylogenetic hypotheses
      based on comparative leaf morphology and habitat preferences or floral
      morphology: (1) L. curdieana is sister to the African L. grandiflora; or (2) it
      is closely related to a group of other African species and the northern
      circumpolar L. aquatica. We tested these hypotheses in a phylogenetic framework
      using DNA sequence data from four plastid DNA regions and the nuclear ITS region.
      These were analyzed using maximum parsimony and Bayesian inference. We obtained
      moderately resolved, partially conflicting phylogenies, supporting that
      accessions of L. grandiflora form the sister group to the rest of the genus and
      that L. curdieana groups with the African taxa, L. africana and L. major, and L.
      aquatica. Thus, the molecular evidence supports the second hypothesis. A
      biogeographic analysis suggests an out-of-southern Africa scenario and several
      dispersal events in the Southern Hemisphere. Past dispersal from southern Africa
      to Australasia is suggested, yet it cannot be excluded that a route via tropical
      Africa and temperate Asia has existed.

PMID- 27864640
TI  - Arabidopsis phospholipase D alpha 1-derived phosphatidic acid regulates
      microtubule organization and cell development under microtubule-interacting drugs
      treatment.
AB  - Phospholipase D (PLD) and its product phosphatidic acid (PA) are emerging as
      essential regulators of cytoskeleton organization in plants. However, the
      underlying molecular mechanisms of PA-mediated microtubule reorganization in
      plants remain largely unknown. In this study, we used pharmacological and genetic
      approaches to analyze the function of Arabidopsis thaliana PLDalpha1 in the
      regulation of microtubule organization and cell development in response to
      microtubule-affecting drugs. Treatment with the microtubule-stabilizing drug
      paclitaxel resulted in less growth inhibition and decreased rightward slant of
      roots, longitudinal alignment of microtubules, and enhanced length of hypocotyl
      epidermal cells in the pldalpha1 mutant, the phenotype of which was rescued by
      exogenous application of PA. Moreover, the pldalpha1 mutant was sensitive to the
      microtubule-disrupting drugs oryzalin and propyzamide in terms of seedling
      survival ratio, left-skewing angle of roots and microtubule organization. In
      addition, both disruption and stabilization of microtubules induced by drugs
      activated PLDalpha1 activity. Our findings demonstrate that in A. thaliana,
      PLDalpha1/PA might regulate cell development by modulating microtubule
      organization in an activity-dependent manner.

PMID- 27864642
TI  - Evolution of kin recognition mechanisms in a fish.
AB  - Both selection and phylogenetic history can influence the evolution of phenotypic
      traits. Here we used recently characterized variation in kin recognition
      mechanisms among six guppy populations to explore the phylogenetic history of
      this trait. Guppies can use two different kin recognition mechanisms: either
      phenotype matching, in which individuals are identified based on comparison with
      a recognition template, or familiarity, in which individuals are remembered based
      on previous interactions. Across the six populations, we identified four
      transitions in recognition mechanism: phenotype matching evolved once and was
      subsequently lost in a single population, whereas familiarity evolved twice.
      Based on a molecular clock, these transitions occurred among populations that had
      diverged on a timescale of hundreds of thousands of years, which is two orders of
      magnitude faster than previously documented transitions in recognition
      mechanisms. A randomization test provided no evidence that recognition mechanisms
      were constrained by phylogeny, suggesting that recognition mechanisms have the
      capacity to evolve rapidly, although the specific selection pressures that may be
      contributing to variation in recognition mechanisms across populations remain
      unknown.

PMID- 27864641
TI  - An open prospective single cohort multicenter study evaluating the novel,
      tapered, conical connection implants supporting single crowns in the anterior and
      premolar maxilla: interim 1-year results.
AB  - OBJECTIVES: The aim of this multicenter prospective clinical study was to
      evaluate anodized tapered implants with a conical connection and integrated
      platform shifting placed in the anterior and premolar maxilla. MATERIALS AND
      METHODS: The study enrolled patients requiring single-tooth restorations in
      healed sites of maxillary anterior and premolar teeth. All implants were
      immediately temporized. Clinical and radiographic evaluations were conducted at
      implant insertion, 6 months, and 1 year. Outcome measures included bone
      remodeling, cumulative survival rate (CSR), success rate, soft-tissue health and
      esthetics, and patient satisfaction. Bone remodeling and pink esthetic score were
      analyzed using Wilcoxon signed-rank tests. CSR was calculated using life table
      analysis. Other soft-tissue outcomes were analyzed using sign tests. RESULTS: Out
      of 97 enrolled patients (102 implants), 87 patients (91 implants) completed the 1
      year visit. Marginal bone remodeling was -0.85 +/- 1.36 mm. After the expected
      initial bone loss, a mean bone gain of 0.11 +/- 1.05 mm was observed between 6
      months and 1 year. The CSR was 99.0%, and the cumulative success rate was 97.0%.
      Partial or full papilla was observed at 30.8% of sites at baseline, 87.2% at 6
      months, and 90.5% at 1 year. Soft-tissue response, esthetics, and patient
      satisfaction all improved during the study period. CONCLUSIONS: Bone gain was
      observed following the expected initial bone loss, and soft-tissue outcomes
      improved suggesting favorable tissue response using anodized tapered conical
      connection implants. CLINICAL RELEVANCE: Rapid stabilization of bone remodeling
      and robust papilla regeneration indicate favorable tissue healing promoted by the
      conical connection, platform-shift design. TRIAL REGISTRATION: clinicaltrials.gov
      NCT02175550.

PMID- 27864643
TI  - Robust representations of individual faces in chimpanzees (Pan troglodytes) but
      not monkeys (Macaca mulatta).
AB  - Being able to recognize the faces of our friends and family members no matter
      where we see them represents a substantial challenge for the visual system
      because the retinal image of a face can be degraded by both changes in the person
      (age, expression, pose, hairstyle, etc.) and changes in the viewing conditions
      (direction and degree of illumination). Yet most of us are able to recognize
      familiar people effortlessly. A popular theory for how face recognition is
      achieved has argued that the brain stabilizes facial appearance by building
      average representations that enhance diagnostic features that reliably vary
      between people while diluting features that vary between instances of the same
      person. This explains why people find it easier to recognize average images of
      people, created by averaging multiple images of the same person together, than
      single instances (i.e. photographs). Although this theory is gathering momentum
      in the psychological and computer sciences, there is no evidence of whether this
      mechanism represents a unique specialization for individual recognition in
      humans. Here we tested two species, chimpanzees (Pan troglodytes) and rhesus
      monkeys (Macaca mulatta), to determine whether average images of different
      familiar individuals were easier to discriminate than photographs of familiar
      individuals. Using a two-alternative forced-choice, match-to-sample procedure, we
      report a behaviour response profile that suggests chimpanzees encode the faces of
      conspecifics differently than rhesus monkeys and in a manner similar to humans.

PMID- 27864645
TI  - Factors influencing and consequences of breeding dispersal and habitat choice in
      female grey seals (Halichoerus grypus) on Sable Island, Nova Scotia.
AB  - Selection of breeding location can influence reproductive success and fitness.
      Breeding dispersal links habitat use and reproduction. This study investigated
      factors affecting breeding dispersal and its reproductive consequences in grey
      seals (Halichoerus grypus) on Sable Island, Nova Scotia. Breeding dispersal
      distance was determined in 692 individually marked, known-age female grey seals
      observed from 2004 to 2014. We used generalized linear mixed-effects models to
      test hypotheses concerning environmental and demographic factors influencing
      breeding dispersal distance and the consequences of dispersal distance on
      offspring weaning mass. Grey seal females rarely exhibited fidelity to previous
      breeding sites. Median dispersal distance between years was 5.1 km. Only 2.9% of
      females returned to a previous breeding site. Breeding dispersal distance was
      affected by parity and density, but effects were small and are presumably of no
      biological significance. Variation in dispersal distance among adult females was
      large. Dispersal distance had no significant influence on offspring weaning mass;
      however, as previously found, pup sex and maternal age did. Although breeding
      location was not important, heavier pups were born in habitats with no tidal or
      storm-surge influence indicating that breeding habitat type did influence
      offspring size at weaning. The lack of site fidelity in grey seals on Sable
      Island is associated with an unpredictable and changing landscape (sand dunes)
      that could make it difficult for females to locate previous breeding locations.
      Although breeding location within habitat type had small consequences on
      offspring weaning mass, we detected no evidence that breeding site selection
      within the habitat had consequences to females.

PMID- 27864647
TI  - Prethrombotic, prothrombotic, thrombophilic states, hypercoagulable state,
      thrombophilia etc.: semantics should be respected even in medical papers.
AB  - The study of prothrombotic or thrombophilic states have drawn considerable
      attention during the past two decades. This was the result of the increasing
      number of thrombotic events, both arterial and venous reported all over the world
      but especially in the developed countries. This wealth of studies and papers have
      not always respected the semantical significance of the various terms used,
      namely prethrombotic state, hypercoagulable state, thrombophilic or prothrombotic
      state, thrombophilia, susceptibility to thrombosis and procoagulant state. This
      review is an attempt to adhere to a correct Semantic format in order to avoid
      confusion and misinterpretations. This is of fundamental importance in order to
      avoid the wrong attribution of a thrombosis to a hypercoagulable or a
      prethrombotic state.

PMID- 27864644
TI  - Targeting and alteration of tight junctions by bacteria and their virulence
      factors such as Clostridium perfringens enterotoxin.
AB  - The integrity of tight junctions, which regulate paracellular permeability, is
      challenged by many bacterial pathogens. This is caused by inflammatory responses
      triggered by pathogens and direct interaction of bacteria or their toxins with
      host epithelial cells. In some cases, tight junction proteins represent receptors
      for cell surface proteins or toxins of the pathogen, such as Clostridium
      perfringens enterotoxin (CPE). CPE causes diarrhea and cramps-the symptoms of a
      common foodborne illness, caused by C. perfringens type A. It uses a subgroup of
      the claudin family of tight junction proteins as receptors and forms pores in the
      membrane of intestinal epithelial cells. Ca2+ influx through these pores finally
      triggers cell damage. In this review, we summarize tight junction targeting and
      alteration by a multitude of different microorganisms such as C. perfringens,
      Escherichia coli, Helicobacter pylori, Salmonella typhimurium, Shigella flexneri,
      Vibrio cholerae, Yersinia enterocolitica, protozoan parasites, and their
      proteins. A focus is drawn towards CPE, the interaction with its receptors,
      cellular, and pathophysiological consequences for the intestinal epithelium. In
      addition, we portend to the use of CPE-based claudin modulators for drug delivery
      as well as diagnosis and therapy of cancer.

PMID- 27864646
TI  - Low-level laser irradiation modulates brain-derived neurotrophic factor mRNA
      transcription through calcium-dependent activation of the ERK/CREB pathway.
AB  - Low-level laser (LLL) irradiation has been reported to promote neuronal
      differentiation, but the mechanism remains unclear. Brain-derived neurotrophic
      factor (BDNF) has been confirmed to be one of the most important neurotrophic
      factors because it is critical for the differentiation and survival of neurons
      during development. Thus, this study aimed to investigate the effects of LLL
      irradiation on Bdnf messenger RNA (mRNA) transcription and the molecular pathway
      involved in LLL-induced Bdnf mRNA transcription in cultured dorsal root ganglion
      neurons (DRGNs) using Ca2+ imaging, pharmacological detections, RNA interference,
      immunocytochemistry assay, Western blot, and qPCR analysis. We show here that LLL
      induced increases in the [Ca2+] i level, Bdnf mRNA transcription, cAMP-response
      element-binding protein (CREB) phosphorylation, and extracellular signal
      regulated kinase (ERK) phosphorylation, mediated by Ca2+ release via inositol
      triphosphate receptor (IP3R)-sensitive calcium (Ca2+) stores. Blockade of Ca2+
      increase suppressed Bdnf mRNA transcription, CREB phosphorylation, and ERK
      phosphorylation. Downregulation of phosphorylated (p)-CREB reduced Bdnf mRNA
      transcription triggered by LLL. Furthermore, blockade of ERK using PD98059
      inhibitor reduced p-CREB and Bdnf mRNA transcription induced by LLL. Taken
      together, these findings establish the Ca2+-ERK-CREB cascade as a potential
      signaling pathway involved in LLL-induced Bdnf mRNA transcription. To our
      knowledge, this is the first report of the mechanisms of Ca2+-dependent Bdnf mRNA
      transcription triggered by LLL. These findings may help further explore the
      complex molecular signaling networks in LLL-triggered nerve regeneration in vivo
      and may also provide experimental evidence for the development of LLL for
      clinical applications.

PMID- 27864650
TI  - Heme oxygenase-1 protects spinal cord neurons from hydrogen peroxide-induced
      apoptosis via suppression of Cdc42/MLK3/MKK7/JNK3 signaling.
AB  - The mechanisms by which oxidative stress induces spinal cord neuron death has not
      been completely understood. Investigation on the molecular signal pathways
      involved in oxidative stress-mediated neuronal death is important for development
      of new therapeutics for oxidative stress-associated spinal cord disorders. In
      current study we examined the role of heme oxygenase-1 (HO-1) in the modulation
      of MLK3/MKK7/JNK3 signaling, which is a pro-apoptotic pathway, after treating
      primary spinal cord neurons with H2O2. We found that MLK3/MKK7/JNK3 signaling was
      substantially activated by H2O2 in a time-dependent manner, demonstrated by
      increase of activating phosphorylation of MLK3, MKK7 and JNK3. H2O2 also induced
      expression of HO-1. Transduction of neurons with HO-1-expressing adeno-associated
      virus before H2O2 treatment introduced expression of exogenous HO-1 in neurons.
      Exogenous HO-1 reduced phosphorylation of MLK3, MKK7 and JNK3. Consistent with
      its inhibitory effect on MLK3/MKK7/JNK3 signaling, exogenous HO-1 decreased H2O2
      induced neuronal apoptosis and necrosis. Furthermore, we found that exogenous HO
      1 inhibited expression of Cdc42, which is crucial for MLK3 activation. In
      addition, HO-1-induced down-regulation of MLK3/MKK7/JNK3 signaling might be
      related to up-regulation of microRNA-137 (mir-137). A mir-137 inhibitor
      alleviated the inhibitory effect of HO-1 on JNK3 activation. This inhibitor also
      increased neuronal death even when exogenous HO-1 was expressed. Therefore, our
      study suggests a novel mechanism by which HO-1 exerted its neuroprotective
      efficacy on oxidative stress.

PMID- 27864651
TI  - All in the family? Analyzing the impact of family history in addition to genotype
      on medullary thyroid carcinoma aggressiveness in MEN2A patients.
AB  - Several guidelines for patients with multiple endocrine neoplasia 2A (MEN2A) take
      into account genotype and family history of medullary thyroid carcinoma (MTC)
      disease aggressiveness. We sought to determine if an association exists
      independent of genotype, which could provide important information for counseling
      MEN2A patients in management of their MTC. Pedigrees of patients with >=5 family
      members with MEN2A were retrospectively reviewed. Analysis was performed among
      kindreds with the most frequently observed codon mutation (RET 634). Familial MTC
      disease aggressiveness was evaluated using: (1) mean age at diagnosis of MTC, (2)
      current mean age of carriers without MTC, (3) proportion of kindred with MTC with
      metastatic disease at diagnosis, (4) proportion of kindred with MTC with
      metastasis/death from MTC as worst outcome, and (5) proportion of kindred with
      disease progression. 170 affected patients from 12 different MEN2A kindreds met
      inclusion criteria. The number of affected family members available for study per
      kindred ranged from 8 to 43 individuals. A difference in mean age of MTC
      diagnosis was found in screened patients (p = 0.01); mean age of MTC-free
      patients did not differ (p = 0.93). No differences were noted among kindreds in
      disease stage at presentation, worst outcome, or progression; marked variation in
      these measures was noted within families. In conclusion, a difference in age of
      MTC diagnosis among different RET 634 kindreds was identified. In contrast,
      notable intra-familial variability in disease aggressiveness was observed. Based
      on these findings, we recommend counseling patients with codon 634 mutations that
      their MTC disease course cannot be predicted by that of their relatives.

PMID- 27864648
TI  - Actomyosin based contraction: one mechanokinetic model from single molecules to
      muscle?
AB  - Bridging the gaps between experimental systems on different hierarchical scales
      is needed to overcome remaining challenges in the understanding of muscle
      contraction. Here, a mathematical model with well-characterized structural and
      biochemical actomyosin states is developed to that end. We hypothesize that this
      model accounts for generation of force and motion from single motor molecules to
      the large ensembles of muscle. In partial support of this idea, a wide range of
      contractile phenomena are reproduced without the need to invoke cooperative
      interactions or ad hoc states/transitions. However, remaining limitations exist,
      associated with ambiguities in available data for model definition e.g.: (1) the
      affinity of weakly bound cross-bridges, (2) the characteristics of the cross
      bridge elasticity and (3) the exact mechanistic relationship between the force
      generating transition and phosphate release in the actomyosin ATPase. Further,
      the simulated number of attached myosin heads in the in vitro motility assay
      differs several-fold from duty ratios, (fraction of strongly attached ATPase
      cycle times) derived in standard analysis. After addressing the mentioned issues
      the model should be useful in fundamental studies, for engineering of myosin
      motors as well as for studies of muscle disease and drug development.

PMID- 27864649
TI  - Cardioprotective effects of omega 3 fatty acids: origin of the variability.
AB  - Since 40 years, it is known that omega-3 poly-unsaturated fatty acids (omega3
      PUFAs) have cardioprotective effects. These include antiarrhythmic effects,
      improvements of autonomic function, endothelial function, platelet anti
      aggregation and inflammatory properties, lowering blood pressure, plaque
      stabilization and reduced atherosclerosis. However, recently, conflicting results
      regarding the health benefits of omega3 PUFAs from seafood or omega3 PUFAs
      supplements have emerged. The aim of this review is to examine recent literature
      regarding health aspects of omega3 PUFAs intake from fish or supplements, and to
      discuss different arguments/reasons supporting these conflicting findings.

PMID- 27864652
TI  - Differences in mammographic density between Asian and Caucasian populations: a
      comparative analysis.
AB  - PURPOSE: Mammographic density is a measurable and modifiable biomarker that is
      strongly and independently associated with breast cancer risk. Paradoxically,
      although Asian women have lower risk of breast cancer, studies of minority Asian
      women in predominantly Caucasian populations have found that Asian women have
      higher percent density. In this cross-sectional study, we compared the
      distribution of mammographic density for a matched cohort of Asian women from
      Malaysia and Caucasian women from Sweden, and determined if variations in
      mammographic density could be attributed to population differences in breast
      cancer risk factors. METHODS: Volumetric mammographic density was compared for
      1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass
      index. We used multivariable log-linear regression to determine the risk factors
      associated with mammographic density and mediation analysis to identify factors
      that account for differences in mammographic density between the two cohorts.
      RESULTS: Compared to Caucasian women, percent density was 2.0% higher among Asian
      women (p < 0.001), and dense volume was 5.7 cm3 higher among pre-menopausal Asian
      women (p < 0.001). Dense volume was 3.0 cm3 lower among post-menopausal Asian
      women (p = 0.009) compared to post-menopausal Caucasian women, and this
      difference was attributed to population differences in height, weight, and parity
      (p < 0.001). CONCLUSIONS: Our analysis suggests that among post-menopausal women,
      population differences in mammographic density and risk to breast cancer may be
      accounted for by height, weight, and parity. Given that pre-menopausal Asian and
      Caucasian women have similar population risk to breast cancer but different dense
      volume, development of more appropriate biomarkers of risk in pre-menopausal
      women is required.

PMID- 27864653
TI  - The developmental competence of oocytes parthenogenetically activated by an
      electric pulse and anisomycin treatment.
AB  - OBJECTIVE: The aim of this study was to investigate the developmental competence
      of oocytes parthenogenetically activated by an electric pulse (EP) and treated
      with anisomycin and to determine whether this method is applicable to somatic
      cell nuclear transfer (SCNT). RESULTS: Embryos derived from porcine oocytes
      parthenogenetically activated by an EP and treatment with 0.01 ug/mL anisomycin
      had a significantly improved in vitro developmental capacity. Furthermore, 66.6%
      of blastocysts derived from these embryos had a diploid karyotype. The blastocyst
      formation rate of cloned embryos was similar between oocytes activated by an EP
      and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP
      and treated with 0.01 ug/mL anisomycin for 4 h. The level of maturation-promoting
      factor was significantly decreased in oocytes activated by an EP and treated with
      anisomycin. Finally, the mRNA expression levels of apoptosis-related genes (Bax
      and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by
      RT-PCR. CONCLUSION: Our results demonstrate that porcine oocyte activation via an
      EP in combination with anisomycin treatment can lead to a high blastocyst
      formation rate in parthenogenetic activation and SCNT experiments.

PMID- 27864654
TI  - A dual substrate kinetic model for cytochrome P450BM3-F87G catalysis:
      simultaneous binding of long chain aldehydes and 4-fluorophenol.
AB  - OBJECTIVE: To develop a model for binding and catalysis associated with the
      stimulation of 4-fluorophenol (4-FP) oxidation in the presence of long chain
      aldehydes by the enzymatic catalyst, cytochrome P450BM3-F87G. RESULTS: A
      variation of the Michaeli-Menten kinetic model was employed to describe
      interactions at the active site of the enzyme, along with computer aided modeling
      approaches. In addition to the hydroquinone product arising from de-fluorination
      of 4-FP, a second product (p-fluorocatechol) was also observed and, like the
      hydroquinone, its rate of formation increased in the presence of the aldehyde.
      When only aldehyde was present with the enzyme, BM3-F87G catalyzed its oxidation
      to the corresponding carboxylic acid; however, this activity was inhibited when 4
      FP was added to the reaction. A 3D computer model of the active site containing
      both aldehyde and 4-FP was generated, guided by these kinetic observations.
      Finally, partitioning between the two phenolic products was examined with an
      emphasis on the conditions directing the initial epoxidation at either the 2,3-
      or 3,4-positions on the substrate. Temperature, reaction time, substrate
      concentration, and the structure of the aldehyde had no substantial effect on the
      overall product ratios, however the NADPH coupling efficiency decreased when
      unsaturated aldehydes were included, or when the temperature of the reaction was
      reduced. CONCLUSIONS: The unsaturated aldehyde, trans-2-decenal, stimulates BM3
      F87G catalyzed oxidation of 4-fluorophenol through a cooperative active site
      binding mode that doesn't influence product distributions or coupling
      efficiencies, while 4-fluorophenol acts as a competitive inhibitor of aldehyde
      oxidation.

PMID- 27864655
TI  - Imitating the effect of amblyopia on VEP-based acuity estimates.
AB  - PURPOSE: Acuity testing based on visual evoked potentials (VEPs) overestimates
      acuity in patients with amblyopia. We hypothesized that distortion and
      fragmentation of the stimulus in amblyopia impede recognition of optotypes, while
      it leaves the pattern onset response in the VEP mostly unaffected, resulting in
      overestimation of acuity. METHODS: Acuity VEPs were recorded in visually normal
      participants with the stimulus degraded by patterned polymethyl methacrylate
      panes, which induce distortion and fragmentation. For comparison, frosted panes
      were used to induce blur through wide-angle scattering. Standard psychophysical
      optotype acuity was recorded under the same conditions. RESULTS: With the
      distorted and fragmented stimuli, the VEP consistently overestimated acuity
      relative to psychophysical optotype acuity. With blurred stimuli, both measures
      were in good agreement. CONCLUSIONS: The data support the assumption that
      stimulus distortion and fragmentation leave VEP-based measures of acuity
      relatively unaffected, resulting in a discrepancy between measures of acuity that
      are based on checkerboard VEPs on one hand and psychophysical optotype
      recognition on the other hand. The technique of stimulus degradation described
      here provides a simple and efficient way of imitating effects that are known from
      amblyopia and may thus serve as a tool in the evaluation of vision tests.

PMID- 27864657
TI  - Erratum to: Vedolizumab Therapy Is Associated with an Improvement in Sleep
      Quality and Mood in Inflammatory Bowel Diseases.

PMID- 27864658
TI  - Conjugates between photosystem I and a carbon nanotube for a photoresponse
      device.
AB  - Photosystem I (PS I) is a large pigment-protein complex embedded in the thylakoid
      membranes that performs light-driven electron transfer across the thylakoid
      membrane. Carbon nanotubes exhibit excellent electrical conductivities and
      excellent strength and stiffness. In this study, we generated PSI-carbon nanotube
      conjugates dispersed in a solution aimed at application in artificial
      photosynthesis. PS I complexes in which a carbon nanotube binding peptide was
      introduced into the middle of the PsaE subunit were conjugated on a single-walled
      carbon nanotube, orienting the electron acceptor side to the nanotube. Spectral
      and photoluminescence analysis showed that the PS I is bound to a single-walled
      carbon nanotube, which was confirmed by transmission electron microscopy.
      Photocurrent observation proved that the photoexcited electron originated from
      PSI and transferred to the carbon nanotube with light irradiation, which also
      confirmed its orientated conjugation. The PS I-carbon nanotube conjugate will be
      a useful nano-optoelectronic device for the development of artificial systems.

PMID- 27864656
TI  - Nitric Oxide and Hydrogen Sulfide Interact When Modulating Gastric Physiological
      Functions in Rodents.
AB  - AIM: The objective was to evaluate the effects of nitric oxide (NO) and hydrogen
      sulfide (H2S) donors and possible interactions between these two systems in
      modulating gastric function. METHODS: Mice received saline, sodium nitroprusside
      (SNP), or sodium hydrosulfite (NaHS), and after 1 h, the animals were killed for
      immunofluorescence analysis of CSE or eNOS expressions, respectively. Other
      groups received saline, SNP, NaHS, Lawesson's reagent (H2S donor), PAG + SNP, L
      NAME, L-NAME + NaHS, or L-NAME + Lawesson's reagent. Then, the gastric secretions
      (mucous and acid), gastric blood flow, gastric defense against ethanol, and
      gastric motility (gastric emptying and gastric contractility) were evaluated.
      RESULTS: SNP and NaHS increased the expression of CSE or eNOS, respectively. SNP
      or Lawesson's reagent did not alter gastric acid secretion but increased mucus
      production, and these effects reverted with PAG and L-NAME treatment,
      respectively. SNP or NaHS increased gastric blood flow and protected the gastric
      mucosa against ethanol injury, and these effects reverted with PAG and L-NAME
      treatments, respectively. SNP delayed gastric emptying when compared with saline,
      and PAG partially reversed this effect. NaHS accelerate gastric emptying, and L
      NAME partially reversed this effect. SNP and NaHS alone induced gastric fundus
      and pylorus relaxation. However, pretreatment with PAG or L-NAME reversed these
      relaxant effects only in the pylorus but not in the gastric fundus. CONCLUSION:
      NO and H2S interact in gastric physiological functions, and this "cross-talk" is
      important in the control of mucus secretion, gastric blood flow, gastric mucosal
      defense, and gastric motility, but not in the control of basal gastric acid
      secretion.

PMID- 27864659
TI  - Immune complexes and complexity: investigating mechanisms of renal disease.
AB  - The deposition of immune complexes is the causal factor in distinct renal
      pathologies, e.g., lupus nephritis and membranous nephritis. The location of
      these deposits within a tissue biopsy is often the key to establishing a
      diagnosis. However, how immune complexes come to be deposited below the vascular
      endothelium was, until now, a mystery, as was their contribution to inducing
      inflammation. A recent paper in Cell by Stamatiades et al. (Cell 164(4):991-1003,
      2016) demonstrates the active transport of immune complexes by the vascular
      endothelial cells and an Fc receptor-dependent uptake by tissue-resident
      macrophages. This leads to the activation of these macrophages and the release of
      pro-inflammatory cytokines, which in turn recruits immune cells from the blood
      into the kidney. The identification of these mechanisms should lead to a better
      stratification of kidney diseases and hopefully to the development of specific
      therapies.

PMID- 27864660
TI  - Effects of CYP2C9 genetic polymorphisms on the pharmacokinetics of celecoxib and
      its carboxylic acid metabolite.
AB  - Celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, is used for the
      treatment of rheumatoid arthritis and osteoarthritis. The predominant hepatic
      metabolism of celecoxib to celecoxib carboxylic acid (CCA) is mediated mainly by
      CYP2C9. We investigated the effects of the major CYP2C9 genetic variants in Asian
      populations, CYP2C9*3 and CYP2C9*13, on the pharmacokinetics of celecoxib and its
      carboxylic acid metabolite in healthy Korean subjects. A single 200-mg oral dose
      of celecoxib was given to 52 Korean subjects with different CYP2C9 genotypes:
      CYP2C9EM (n = 26; CYP2C9*1/*1), CYP2C9IM (n = 24; CYP2C9*1/*3 and *1/*13), and
      CYP2C9PM (n = 2; CYP2C9*3/*3). Celecoxib and CCA concentrations in plasma samples
      collected up to 48 or 96 h after drug intake were determined by HPLC-MS/MS. The
      mean area under the plasma concentration-time curve (AUC0-infinity) of celecoxib
      was increased 1.63-fold (P < 0.001), and the apparent oral clearance (CL/F) of
      celecoxib was decreased by 39.6% in the CYP2C9IM genotype group compared with
      that of CYP2C9EM (P < 0.001). The overall pharmacokinetic parameters for
      celecoxib in CYP2C9*1/*13 subjects were similar to those in CYP2C9*1/*3 subjects.
      Two subjects with CYP2C9PM genotype both showed markedly higher AUC0-infinity,
      prolonged half-life, and lower CL/F for celecoxib than did subjects with CYP2C9EM
      and IM genotypes. CYP2C9*3 and CYP2C9*13 variant alleles significantly affected
      the plasma concentration of celecoxib.

PMID- 27864662
TI  - Erratum to: Plant Posters.

PMID- 27864663
TI  - Mesenchymal stem cells attenuate hydrogen peroxide-induced oxidative stress and
      enhance neuroprotective effects in retinal ganglion cells.
AB  - The apoptosis of retinal ganglion cells leads to visual impairment and blindness
      in ocular neurodegenerative diseases, especially in diabetic retinopathy (DR).
      Mounting evidence suggests that oxidative stress contributes to the pathogenesis
      of DR. In the present study, we investigated whether bone mesenchymal stem cells
      (BMSCs) have protective ability to relieve hydrogen peroxide (H2O2)-induced
      injury on retinal ganglion cells in vitro. An immortalized retinal ganglion
      cells, RGC-5 cells, were exposed to an indicated concentration of H2O2 for 24 h.
      Cell viability was analyzed by CCK-8 assay to find out a certain concentration to
      build H2O2 oxidative damage model. Morphological changes in RGC-5 cells were
      observed under optical microscope, and cell apoptosis was detected with Hoechst
      fluorescence staining. Then, BMSCs were co-cultured with RGC-5 cells in a
      transwell culture system for 24 h and 48 h. Flow cytometry was performed to
      qualify the apoptosis rate of RGC-5 cells. Conditioned medium was collected for
      evaluation the inflammatory cytokines by ELISA. The content of intracellular
      malondialdehyde (MDA) and superoxide dismutase (SOD) was assayed by
      thiobarbituric acid and xanthine oxidase method, respectively. qRT-PCR and ELISA
      were conducted for analysis of the expression changes in brain-derived
      neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF), respectively.
      After H2O2 exposure, the morphological varieties were observed as cytoplasm
      shrinking and paramorphia together with nuclear gathering. Meanwhile, the
      apoptotic cells had hyperfluorescence with Hoechst 33258 staining. Co-culture
      with BMSCs significantly inhibited retinal cell death. It was found that BMSCs
      reduced H2O2-induced inflammatory factors IL-1beta and TNF-alpha, down-regulated
      intracellular oxidant factor MDA, up-regulated intracellular antioxidant factor
      SOD, and increased neurotrophins BDNF and CNTF expression. BMSCs may enhance
      protective effect of RGC-5 cells in H2O2-induced damage through improving
      antioxidant capacity, inhibiting pro-inflammatory cytokine secretion, and
      promoting neurotrophin expression.

PMID- 27864664
TI  - Radiofrequency ablation of pulmonary metastases from sarcoma: single-center
      retrospective evaluation of 46 patients.
AB  - PURPOSE: This retrospective, single-center study evaluated radiofrequency (RF)
      ablation for pulmonary metastases of sarcoma. MATERIALS AND METHODS: Forty-six
      patients with sarcoma (144 pulmonary metastases) underwent 88 RF ablation
      sessions. Data regarding local tumor progression, efficacy, procedural adverse
      events (AEs; National Cancer Institute Common Terminology Criteria for Adverse
      Events, version 4.0), overall survival (OS), and OS-associated prognostic factors
      were retrospectively evaluated using univariate analyses. RESULTS: Local
      progression occurred in 22 of 144 tumors (15.3%). Primary and secondary efficacy
      rates were 83.5 and 90.0% at 1 year and 76.3 and 81.4% at 2 years, respectively.
      Seventy-three grade 1 AEs, 33 grade 2 AEs, and no grade >= 3 AEs were observed.
      Twenty-eight patients (60.9%) remained alive and 18 died, yielding 1-, 2-, and 3
      year OS rates of 80.6, 70.1, and 47.1% (median survival time, 31.7 months).
      Univariate analysis revealed extrapulmonary metastasis (P = 0.005), noncurative
      RF ablation (P = 0.009), and a post-RF ablation disease-free interval of <=12
      months (P = 0.015) as significant negative prognostic factors. CONCLUSION: RF
      ablation is safe, offers good local control, and may be a viable treatment option
      for pulmonary metastasis of sarcoma.

PMID- 27864661
TI  - Molecular Anti-inflammatory Mechanisms of Retinoids and Carotenoids in
      Alzheimer's Disease: a Review of Current Evidence.
AB  - Alzheimer's disease (AD) is considered as one of the most prevalent
      neurodegenerative disorders characterized by progressive loss of mental function
      and ability to learn. AD is a multifactorial disorder. Various hypotheses are
      suggested for the pathophysiology of AD including "Abeta hypothesis," "tau
      hypothesis," and "cholinergic hypothesis." Recently, it has been demonstrated
      that neuroinflammation is involved in the pathogenesis of AD. Neuroinflammation
      causes synaptic dysfunction and neuronal death within the brain. Excessive
      production of pro-inflammatory mediators induces Abeta peptide
      production/accumulation and hyperphosphorylated tau generating inflammatory
      molecules and cytokines. These inflammatory molecules disrupt blood-brain barrier
      integrity and increase the production of Abeta42 oligomers. Retinoids and
      carotenoids are potent antioxidants and anti-inflammatory agents having
      neuroprotective properties. They are able to prevent disease progression through
      several mechanisms such as suppression of Abeta peptide production/accumulation,
      oxidative stress, and pro-inflammatory mediator's secretion as well as
      improvement of cognitive performance. These observations, therefore, confirm the
      neuroprotective role of retinoids and carotenoids through multiple pathways.
      Therefore, the administration of these nutrients is considered as a promising
      approach to the prevention and/or treatment of AD in the future. The aim of this
      review is to present existing evidences regarding the beneficial effects of
      retinoids and carotenoids on AD's risk and outcomes, seeking the mechanism of
      their action.

PMID- 27864666
TI  - Evaluation of Serum Trace Element Levels and Superoxide Dismutase Activity in
      Patients with Inflammatory Bowel Disease: Translating Basic Research into
      Clinical Application.
AB  - The relationship of minerals and trace elements with inflammatory bowel disease
      (IBD) is complex. Alterations in their metabolism can be induced by the diseases
      and their complications. To study the role of trace elements in IBD patients'
      serum zinc and copper and their related enzymes, including superoxide dismutase
      (SOD), activity were measured in patients with IBD patients as well as in healthy
      subjects. In addition, the correlation between serum trace element levels,
      albumin, total protein, urea level, copper/zinc ratio, and disease activity (DA)
      was determined in these subjects. Serum samples were obtained from 35 patients
      (19 ulcerative colitis (UC) and 16 Crohn's disease (CD)) in the active phase of
      the disease and 30 healthy control subjects. Serum levels of zinc, copper, SOD
      activity, albumin, total protein, and urea were measured. The results were
      compared between the two groups using independent Student's t test in statistical
      analysis. Serum levels of zinc, SOD activity, albumin, and total protein were
      significantly lower (P < 0.05) in patients than controls, while serum urea level
      was significantly higher in patients compared to controls. Copper concentrations
      did not differ between patients with IBD (mean +/- SD, 58.8 +/- 20.7 MUg/d) and
      controls (55.57 +/- 12.6 MUg/d). Decreased levels of zinc and SOD activity are
      associated with increased inflammatory processes indicating inappropriate
      antioxidant system in patients with IBD. Additionally, lower levels of albumin
      and total protein with higher level of urea reflect metabolic problems in liver
      system.

PMID- 27864665
TI  - Risk factors for bacteremia in urinary tract infections attended in the emergency
      department.
AB  - Urinary tract infections (UTI) are common in emergency departments (ED), and at
      least 15% of them are bacteremic. However, there are few data on how to predict
      which patients are at high risk of developing bacteremic UTI (b-UTI). We
      performed a retrospective observational cohort study including patients diagnosed
      with UTI who were admitted to the ED of a tertiary-care hospital in Spain. We
      included only those patients in whom blood cultures were performed. A nomogram
      for b-UTI was developed as visualizations of a logistic regression model. Two
      hundred and thirteen patients with UTI were finally included, 108 of them
      developed b-UTI (50.7%). The mean age was 60.5 +/- 21.4 years. A previous
      urologic disease was present in 45.5%, 12 out of 213 patients (5.6%) had a
      urologic tumor (10.2% in b-UTI group vs. 1% in non b-UTI, p = 0.003), and 4.2%
      were kidney transplant recipients. In a multivariate analysis, variables
      associated with b-UTI were: solid organ malignancy (OR 3.19; CI 95% 1.01-10.03, p
      = 0.04), elevated neutrophil count (more than 80% of neutrophils) (OR 5.84; CI
      95% 2.13-15.99, p = 0.0006), elevated C reactive protein (OR 1.046; CI 95% 1.006
      1.087, p = 0.022), and pyuria (presence of >=50 white cells per high-power field
      of urine) (OR 4.43; CI 95% 1.94-10.11, p = 0.0004). The presence of solid tumor,
      elevated neutrophil count, elevated C reactive protein, and pyuria are
      independent risk factors that could be useful in anticipating the development of
      bacteremia in patients with UTI seen in the ED.

PMID- 27864667
TI  - Examining the Impact of Rehospitalization on Healthcare Cost of Myocardial
      Infarction Patients in Beijing: A Retrospective Observational Study.
AB  - INTRODUCTION: To examine the impact of rehospitalization on the healthcare
      expenditure of myocardial infarction (MI) patients in Beijing. METHODS:
      Retrospective data of MI patients were retrieved from the Beijing Medical
      Insurance Database, an administrative database of social medical reimbursement
      activities for the urban population in Beijing, China. Ten percent of patients
      diagnosed with MI from January 1 to December 31, 2012 were randomly selected and
      their first hospitalization was considered as the index event. Their hospital
      utilization after the index event was extracted till September 30, 2013.
      Rehospitalization was defined as an event of hospital admission due to the same
      diagnosis and with a time interval of at least 14 days from the most recent
      admission. The healthcare cost of patients was analyzed, including inpatient cost
      and outpatient cost. Patients' demographic characteristics, co-morbidities, and
      length of hospital stay were also collected from the database. RESULTS: Of the
      1235 MI patients identified, 335 (mean age of 66.14 +/- 15.04 years; 84.18%
      males) had rehospitalization. The rate of MI recurrence was 27.13%. The annual
      healthcare expense was significantly higher for MI patients with
      rehospitalization compared to MI patients without rehospitalization (99,920.43 +/
      84,113.52 CNY vs. 58,877.89 +/- 93,942.90 CNY; P < 0.001). The significant
      positive predictors of incurring healthcare expenditure were male gender, age 45
      years old or more, length of stay at first hospital admission, whether having
      rehospitalization (yes/no), co-morbidity (heart failure and diabetes), and
      admission to a tertiary hospital at first hospital admission. CONCLUSION: There
      was a high risk of MI recurrence for patients in Beijing. The annual healthcare
      cost of MI patients with rehospitalization was significantly higher than MI
      patients without rehospitalization. Male patients of 45 years old or more with
      heart failure and diabetes are likely to incur higher healthcare expenditure.

PMID- 27864669
TI  - Subaxial cervical spine trauma.
AB  - Subaxial cervical spine trauma is common and an often missed diagnosis. Accurate
      and efficient diagnosis and management is necessary to avoid devastating
      complications such as spinal cord injury. Several classification schemes have
      been devised to help categorize fractures of the subaxial spine and define
      treatment algorithms. The Subaxial Cervical Spine Injury Classification System
      (SLIC) is widely used and evaluates not only fracture morphology but also
      considers ligamentous injury and neurological status in surgical decision making.
      However, interobserver reliability is poor, which proves to be the defining
      pitfall of this tool. More modern classification systems have been developed,
      which aim to improve the interobserver reliability; however, further large-scale
      studies are needed for more definitive evaluation. Overall, treatment of subaxial
      cervical spine injuries should include a protocol with initial trauma evaluation,
      leading to expedient operative intervention if indicated. Surgical techniques
      include both anterior and posterior approaches to the cervical spine depending on
      fracture classification.

PMID- 27864668
TI  - Unproven Therapies for Diabetes and Their Implications.
AB  - Diabetes is a chronic disease and is one of the leading causes of morbidity and
      mortality worldwide. Being an ancient disease, many individuals follow
      complementary and alternative medicinal (CAM) therapies for either the cure or
      prevention of the disease. The popularity of these practices among the general
      public is in no way a testimony to their safety and efficacy. Due to the
      possibility of undesirable interactions with conventional medicines, it is
      imperative that patients are asked about CAM use during patient assessment.
      Patient- and physician-targeted awareness programs on various aspects of CAM use
      must be initiated to create a better understanding of evidence-based use of these
      practices. In addition, there should be guidelines in place based on clinical
      trial outcomes, and stricter regulations need to be enforced on CAM practices to
      ensure their safety and effectiveness.

PMID- 27864670
TI  - Relationship Between Vitamin D Deficiency and the Components of Metabolic
      Syndrome in Patients with Morbid Obesity, Before and 1 Year After Laparoscopic
      Roux-en-Y Gastric Bypass or Sleeve Gastrectomy.
AB  - BACKGROUND: Vitamin D deficiency (VDD) is associated with obesity and metabolic
      syndrome (MS). After bariatric surgery (BS), high rates of VDD often persist and
      some patients are refractory to the resolution of comorbidities. The aim of the
      present study is to analyse the relationship between the levels of vitamin D and
      the persistence of MS components at 12 months after BS, according to the surgical
      technique used. METHODS: We performed a retrospective study of 46 patients
      undergoing BS: 23 underwent laparoscopic Roux-en-Y gastric bypass (LRYGBP) and 23
      laparoscopic sleeve gastrectomy (LSG). These patients had an average BMI of 45
      kg/m2 (34-63). Levels of vitamin D were classified as deficient (<20 ng/dl),
      insufficient (20-30 ng/dl) or normal (>30 ng/dl) and analysed in relation to the
      components of MS (high blood pressure (HBP), dyslipidaemia (DL) and type 2
      diabetes mellitus (T2DM) preoperatively and 12 months after surgery. RESULTS: VDD
      was observed in 77% of the patients prior to surgery. There were no significant
      associations between predisposing factors and baseline vitamin D. After surgery,
      plasma levels of vitamin D increased in both groups, but only 18% of the patients
      achieved normal values. Both groups had achieved significant improvements in MS
      components. Thus, 63% of all the patients achieved complete resolution of HBP,
      54% that of DL and 77% that of T2DM. Moreover, MS was present in 11% of the
      patients, compared to 63% at baseline, and the MS resolution rate was 83%, with
      no significant differences between LRYGBP and LSG. CONCLUSIONS: There is a
      relationship between VDD and persistence of MS, and particularly so with T2DM.
      VDD could represent a predictor of MS persistence at 12 months after surgery.

PMID- 27864671
TI  - Effects of polymer-based, silver nanoparticle-coated silicone splints on the
      nasal mucosa of rats.
AB  - Infection is a serious complication after nasal packing that otolaryngologists
      seek to avoid. The aim of this study is to investigate the use of silver (Ag)
      nanoparticle, which serves as antimicrobial agents, with nasal tampons. The study
      design is an experimental animal model and the setting is tertiary referral
      center. Twenty-four rats were randomized into the following four groups: (1)
      control group (n = 6); (2) silicone nasal splint (SNS) group (n  =  6); (3)
      polypropylene-grafted polyethylene glycol (PP-g-PEG) amphiphilic graft copolymer
      coated SNS group (n  =  6); and (4) Ag nanoparticle-embedded PP-g-PEG (Ag-PP-g
      PEG) amphiphilic graft copolymer-coated SNS group (n  =  6). These tampons were
      applied to rats for 48 h, after which they were removed in a sterile manner, and
      the rats were sacrificed. The nasal septa of the rats were excised, and
      assessments of tissue changes in the nasal mucosa were compared among the groups.
      The removed tampons were microbiologically examined, and quantitative analyses
      were made. When the groups were compared microbiologically, there were no
      significant differences in bacterial colonization rates of coagulase-negative
      Staphylococcus spp. among the three groups (p = 0.519), but there was a
      statistically significant difference among bacterial colonization rates of
      Heamophilus parainfluenzae and Corynebacterium spp. (p = 0.018, p = 0.004). We
      found that H. parainfluenzae grew less robustly in the Ag-PP-g-PEG than the PP-g
      PEG group (p = 0.017). However, we found no significant difference between the Ag
      PP-g-PEG and SNS groups, or between the SNS and PP-g-PEG groups. The growth of
      Corynebacterium spp. did not differ significantly between the Ag-PP-g-PEG and SNS
      groups (p = 1.000). When Group 4 was compared with Group 2, the former showed
      less inflammation. Compared with other tampons, Ag-PP-g-PEG amphiphilic graft
      copolymer-coated silicone nasal tampons caused less microbiological colonization
      and inflammation. Therefore, the use of these tampons may prevent secondary
      infections and reduce the risk of developing complications by minimizing tissue
      damage.

PMID- 27864672
TI  - Rhinophototherapy in persistent allergic rhinitis.
AB  - Previous published results have revealed that Rhinolight(r) intranasal
      phototherapy is safe and effective in intermittent allergic rhinitis. The present
      objective was to assess whether phototherapy is also safe and effective in
      persistent allergic rhinitis. Thirty-four patients with persistent allergic
      rhinitis were randomized into two groups; twenty-five subjects completed the
      study. The Rhinolight(r) group was treated with a combination of UV-B, UV-A, and
      high-intensity visible light, while the placebo group received low-intensity
      visible white light intranasal phototherapy on a total of 13 occasions in 6
      weeks. The assessment was based on the diary of symptoms, nasal inspiratory peak
      flow, quantitative smell threshold, mucociliary transport function, and ICAM-1
      expression of the epithelial cells. All nasal symptom scores and nasal
      inspiratory peak flow measurements improved significantly in the Rhinolight(r)
      group relative to the placebo group and this finding persisted after 4 weeks of
      follow-up. The smell and mucociliary functions did not change significantly in
      either group. The number of ICAM-1 positive cells decreased non-significantly in
      the Rhinolight(r) group. No severe side-effects were reported during the
      treatment period. These results suggest that Rhinolight(r) treatment is safe and
      effective in persistent allergic rhinitis.

PMID- 27864673
TI  - Proteomic analysis of differentially expressed proteins in the two developmental
      stages of Ichthyophthirius multifiliis.
AB  - Ichthyophthirius is a severe disease of farmed freshwater fish caused by the
      parasitic ciliate Ichthyophthirius multifiliis (Ich). This disease can lead to
      considerable economic loss, but the protein profiles in different developmental
      stages of the parasite remain unknown. In the present study, proteins from
      trophonts and theronts of Ich were identified by isobaric tags for relative and
      absolute quantitation (iTRAQ). A total of 2300 proteins were identified in the
      two developmental stages, of which 1520 proteins were differentially expressed.
      Among them, 84 proteins were uniquely expressed in the theronts stage, while 656
      proteins were expressed only in trophonts. The differentially expressed proteins
      were catalogued (assorted) to various functions of Ich life cycle, including
      biological process, cellular component, and molecular function that occur at
      distinct stages. Using a 1.5-fold change in expression as a physiologically
      significant benchmark, a lot of differentially expressed proteins were reliably
      quantified by iTRAQ analysis. Two hundred forty upregulated and 57 downregulated
      proteins in the trophonts stage were identified as compared with theronts. The
      identified proteins were involved in various functions of the I. multifiliis life
      cycle, including binding, catalytic activity, structural molecule activity, and
      transporter activity. Further investigation of the transcriptional levels of
      periplasmic immunogenic protein, transketolase, zinc finger, isocitrate
      dehydrogenase, etc., from the different protein profiles using quantitative RT
      PCR showed identical results to the iTRAQ analysis. This work provides an
      effective resource to further our understanding of Ich biology, and lays the
      groundwork for the identification of potential drug targets and vaccines
      candidates for the control of this devastating fish pathogen.

PMID- 27864674
TI  - Interactions between Giardia duodenalis Sm proteins and their association with
      spliceosomal snRNAs.
AB  - Giardia duodenalis is a parasite that colonises the intestines of humans and
      other vertebrates, causing diarrhoea and poor nutrient absorption. G. duodenalis
      is sometimes considered an early diverging eukaryote, and its genome exhibits
      simplified molecular machinery for many cellular processes, which makes it an
      interesting model to study. The spliceosome, one of the most complex molecular
      machines in the eukaryotic cell, is responsible for intron excision and exon
      splicing. Just over a decade ago, it was believed that the G. duodenalis genome
      did not contain introns or undergo splicing. Research now shows that this
      speculation was incorrect and that uncommon mechanisms, such as trans-splicing
      from different genes, occur. In silico studies of the parasite suggest the
      possibility of a simplified spliceosome and spliceosomal small nuclear RNA
      (snRNA) candidates; however, none of these components have been identified in
      vivo. Here, we developed a strategy to study the in vivo expression, interactions
      and localisation of these spliceosome components in G. duodenalis. Haemagglutinin
      (HA)-tagged SmB and SmD3 proteins, which form part of the spliceosome core, were
      overexpressed in the parasite. Immunoprecipitation with anti-HA revealed that the
      SmD3 protein is associated with the proteins SmB, SmD1, SmD2, SmE and SmF in
      vivo. In addition, the U1, U2 and U4 snRNA candidates reported previously were
      found in the protein complex, suggesting that these molecules are spliceosomal
      snRNAs of G. duodenalis and they contained a 2,2,7-trimethylguanosine
      modification at their 5' end. Our data indicate that the actively expressed
      spliceosome in G. duodenalis is similar to that of highly evolved protists and
      higher animals.

PMID- 27864675
TI  - Drugs Affecting TRP Channels.
AB  - Chronic obstructive pulmonary disease (COPD) and asthma are both common
      respiratory diseases that are associated with airflow reduction/obstruction and
      pulmonary inflammation. Whilst drug therapies offer adequate symptom control for
      many mild to moderate asthmatic patients, severe asthmatics and COPD patients
      symptoms are often not controlled, and in these cases, irreversible structural
      damage occurs with disease progression over time. Transient receptor potential
      (TRP) channels, in particular TRPV1, TRPA1, TRPV4 and TRPM8, have been implicated
      with roles in the regulation of inflammation and autonomic nervous control of the
      lungs. Evidence suggests that inflammation elevates levels of activators and
      sensitisers of TRP channels and additionally that TRP channel expression may be
      increased, resulting in excessive channel activation. The enhanced activity of
      these channels is thought to then play a key role in the propagation and
      maintenance of the inflammatory disease state and neuronal symptoms such as
      bronchoconstriction and cough. For TRPM8 the evidence is less clear, but as with
      TRPV1, TRPA1 and TRPV4, antagonists are being developed by multiple companies for
      indications including asthma and COPD, which will help in elucidating their role
      in respiratory disease.

PMID- 27864676
TI  - Anti-IgE and Biologic Approaches for the Treatment of Asthma.
AB  - Current asthma treatments are effective for the majority of patients with mild-to
      moderate disease. However, in those with more severe refractory asthma, agents
      other than inhaled corticosteroids and beta-agonists are needed both to better
      manage this group of patients and to avoid the side effects of high-dose
      corticosteroids and the social and personal hardship endured. Several biological
      pathways have been targeted over the last 20 years, and this research has
      resulted in pharmacological approaches to attempt to better treat patients with
      severe refractory asthma. The flagship of the biologics, the anti-IgE monoclonal
      antibody, omalizumab, has proven efficacious in selected subgroups of asthma
      patients. Tailoring asthma treatments to suit specific subtypes of asthma
      patients is in keeping with ideals of personalized medicine. Research in the
      complex interplay of allergens, epithelial host defenses, cytokines, and innate
      and adaptive immunity interactions has allowed better understanding of the
      mechanics of allergy and inflammation in asthma. As a result, new biologic
      treatments have been developed that target several different phenotypes and
      endotypes in asthma. As knowledge of the efficacy of these biological agents in
      asthma emerges, as well as the type of patients in whom they are most beneficial,
      the movement toward personalized asthma treatment will follow.

PMID- 27864677
TI  - Glucocorticoids.
AB  - The most effective anti-inflammatory drugs used to treat patients with airways
      disease are topical glucocorticosteroids (GCs). These act on virtually all cells
      within the airway to suppress airway inflammation or prevent the recruitment of
      inflammatory cells into the airway. They also have profound effects on airway
      structural cells to reverse the effects of disease on their function.
      Glucorticosteroids act via specific receptors-the glucocorticosteroid receptor
      (GR)-which are a member of the nuclear receptor family. As such, many of the
      important actions of GCs are to modulate gene transcription through a number of
      distinct and complementary mechanisms. Targets genes include most inflammatory
      mediators such as chemokines, cytokines, growth factors and their receptors. GCs
      delivered by the inhaled route are very effective for most patients and have few
      systemic side effects. However, in some patients, even high doses of topical or
      even systemic GCs fail to control their disease. A number of mechanisms relating
      to inflammation have been reported to be responsible for the failure of these
      patients to respond correctly to GCs and these provide insight into GC actions
      within the airways. In these patients, the side-effect profile of GCs prevent
      continued use of high doses and new drugs are needed for these patients.
      Targeting the defective pathways associated with GC function in these patients
      may also reactivate GC responsiveness.

PMID- 27864678
TI  - Polymorphic Variation in FFA Receptors: Functions and Consequences.
AB  - Overfeeding of fat can cause various metabolic disorders including obesity and
      type 2 diabetes (T2D). Diet provided free fatty acids (FFAs) are not only
      essential nutrients, but they are also recognized as signaling molecules, which
      stimulate various important biological functions. Recently, several G protein
      coupled receptors (GPCRs), including FFA1-4, have been identified as receptors of
      FFAs by various physiological and pharmacological studies. FFAs exert
      physiological functions through these FFA receptors (FFARs) depending on carbon
      chain length and degree of unsaturation. Functional analyses have revealed that
      several important metabolic processes, such as peptide hormone secretion, cell
      maturation and nerve activities, are regulated by FFARs and thereby FFARs
      contribute to the energy homeostasis through these physiological functions.
      Hence, FFARs are expected to be promising pharmacological targets for metabolic
      disorders since imbalances in energy homeostasis lead to metabolic disorders. In
      human, it is established that different responses of individuals to endogenous
      ligands and chemical drugs may be due to differences in the ability of such
      ligands to activate nucleotide polymorphic variants of receptors. However, the
      clear links between genetic variations that are involved in metabolic disorders
      and polymorphisms receptors have been relatively difficult to assess. In this
      review, I summarize current literature describing physiological functions of
      FFARs and genetic variations of those receptors to discuss the potential of FFARs
      as drug targets for metabolic disorders.

PMID- 27864679
TI  - [Prescription of antimalarial drugs in the pediatric ward of the National
      Hospital of Lamorde, in Niamey].
AB  - In Niger, malaria is a major public health problem, due to the high number of
      deaths that are attributable to it and because of its heavy weight and
      socioeconomic status. The objective of this study was to contribute to the
      inventory of medical practices to rationalize the use of medicines and minimize
      the resistance phenomenon. This is a prospective study, which took place from May
      1 to July 31, 2009, in the pediatric ward of the National Hospital of Lamorde. It
      concerned children aged from 0 to 14 years hospitalized and having received one
      or more antimalarial drugs during at least 24 h. During the 3 months of the
      study, 1,248 children had been admitted in the department. Among them, 881
      children received antimalarial treatment, i.e., 70.5% with prescriptions. Malaria
      was confirmed by microscopy in 410 children, i.e., 46.5% of the sick children
      received antimalarial treatment. Prescription control was deemed noncompliant in
      258 patients, i.e., 29.3% of the total. Treatments based on microscopic diagnosis
      are one of the strategies that will help to streamline the use of antimalarial
      drugs to improve their effectiveness and efficiency and also to reduce the risk
      of emergence of resistance.

PMID- 27864680
TI  - The transitional vertebra and sacroiliac joint dysfunction association.
AB  - PURPOSE: The purpose of this study was to investigate whether transitional
      vertebrae contribute to the development of sacroiliac joint dysfunction. The
      prevalence of transitional vertebrae in patients with lumbar pain was determined
      during this process, and the prevalence of sacroiliac dysfunction was compared
      between patients with low back pain and healthy volunteers. METHODS: 700
      subjects, 500 with low back pain and 200 healthy volunteers were included in this
      study. Five tests were applied to all participants to determine sacroiliac joint
      dysfunction. Positivity in three tests was regarded as dysfunction. Lateral
      lumbosacral and Ferguson angle X-rays were taken from the group with low back
      pain. The patient was evaluated a specialist radiologist in terms of presence or
      absence of transitional vertebrae, and if identified, what type. RESULTS:
      Transitional vertebrae were determined in 26% (n = 130) of the patients with low
      back pain. Type 1a was determined in 20%, type 1b in 10%, type 2a in 26.9%, type
      2b in 30.8%, type 3a in 0.8%, type 3b in 4.6% and type 4 in 6.9%. The prevalence
      of sacroiliac joint dysfunction in the low back pain group (15.4%) and the
      prevalence of sacroiliac joint dysfunction in cases of transitional vertebra
      (28.5%) were significantly higher compared to the control groups (p < 0.05).
      CONCLUSION: Sacroiliac joint dysfunction must be considered when investigating
      the etiology of low back pain. Particular sensitivity must be exhibited on this
      subject in patients with transitional vertebrae.

PMID- 27864681
TI  - Are sagittal spinopelvic radiographic parameters significantly associated with
      quality of life of adult spinal deformity patients? Multivariate linear
      regression analyses for pre-operative and short-term post-operative health
      related quality of life.
AB  - PURPOSE: To evaluate the association in ASD patients between spinopelvic sagittal
      parameters and health-related quality of life (HRQL), adjusted for demographic
      and surgical variables. METHODS: We constructed multiple linear regression models
      to investigate pre-operative (PreOp) and 6-month post-operative (PostOp) HRQL as
      assessed by the Oswestry Disability Index (ODI), with sagittal parameters as
      independent variables adjusted for potential confounders, such as age, sex, body
      mass index, past spine surgery, types of surgical treatment, and complications.
      RESULTS: A total of 204 patients (164 women, 40 men, mean age 53.1 years) were
      included in this study. In multivariate models for PreOp ODI, no significant
      association was observed between PreOp HRQL and sagittal parameters when adjusted
      for covariates. Interestingly, age, sex, American Society of Anesthesiologists
      score, and body mass index were still significantly associated with PreOp HRQL.
      In contrast to PreOp analysis, there was a significant association between PostOp
      worse HRQL (higher ODI) and positive T1 sagittal tilt (T1ST: the angle between a
      line drawn from the center of the femoral head axis to the midpoint of the T1
      vertebral body and a vertical line). Sagittal vertical axis had a weaker
      association with HRQL than T1ST. PostOp ASD patients lose flexibility in the
      fused spinal segment, and might be predisposed to symptoms related to spinal
      sagittal malalignment due to limited compensatory ability to maintain a balanced
      standing posture. Interestingly, in patients with sagittal imbalance, low pelvic
      tilt (PT) of <20 was significantly associated with PostOp worse HRQL; this
      suggests that lack of pelvic compensatory ability can cause significant
      disability after ASD surgery. CONCLUSIONS: Pre-operatively, the impact of
      sagittal parameters on HRQL was not as strong as reported in the previous studies
      that used univariate analysis. Not only sagittal parameters, but also the pre
      operative patient's general condition should be carefully reviewed when
      considering indication for ASD surgery. In contrast, although this is a short
      term follow-up study, PostOp HRQL was significantly associated with sagittal
      parameters. When ASD surgery has been indicated, restoration of spinal sagittal
      alignment is certainly important for PostOp HRQL.

PMID- 27864682
TI  - Posterior implant removal in patients with thoracolumbar spine fractures: long
      term results.
AB  - PURPOSE: Debate remains whether posterior implants after thoracolumbar spine
      fracture stabilization should be removed routinely or only in symptomatic cases.
      Implant related problems might be resolved or even prevented but removal includes
      secondary risks. The aim of this study was to evaluate safety, patient
      satisfaction and quality of life after implant removal. METHODS: A retrospective
      cohort study was performed concerning 102 patients that underwent posterior
      implant removal after stabilization of a traumatic thoracolumbar fracture between
      2003 and 2015. Patients were invited to fill in SF-36, EQ-5D and RMDQ
      questionnaires after implant removal. Additionally, questions concerning
      satisfaction were presented. Cobb angles before and after removal were measured
      and in- or decrease of symptoms was gathered from hospital charts. RESULTS: Mean
      age at removal was 38 years and time from implant removal to questionnaire was
      approximately 7 years, 62 patients filled in the questionnaires. Complications
      were present in 8% and quality of life was reported as fairly good. Patients had
      less back pain related disability compared to chronic low back pain patients.
      After removal there was a kyphosis increase which did not correspond with
      worsened clinical outcome. Removal decreased most symptoms and even asymptomatic
      patients reported benefit in most cases. An increase of symptoms after removal
      was reported in 11% of patients. CONCLUSION: Implant removal is generally safe
      and provides high patient satisfaction. Overall, patients have a fairly good
      quality of life. Most symptomatic and asymptomatic patients report benefit from
      removal. However, low risks of complications and increase of symptoms have to be
      weighted for individual patients.

PMID- 27864683
TI  - Cervical sagittal alignment variations in adolescent idiopathic scoliosis
      patients treated with thoraco-lumbo-sacral orthosis.
AB  - PURPOSE: Thoraco-lumbo-sacral orthosis (TLSO) is an effective treatment in
      adolescent idiopathic scoliosis (AIS) patients, but cervical sagittal alignment
      (CSA) variations after bracing have never been evaluated. The purpose of this
      study was to assess changes in CSA before, during and after TLSO treatment, and
      to determine whether patients developed cervical pain. METHODS: This was a
      retrospective study in 38 AIS patients (33 females; mean age 10.8 years) treated
      by TLSO. Patients were Risser 0 (n = 34) or 1 (n = 4). Major curve deformity (MC)
      in the coronal plane and cervical (CSA), thoracic (TSA) and lumbar (LSA) sagittal
      alignment were evaluated radiographically at start of treatment (t 0), after 1
      month of brace treatment (t 1), and 1 year after end of treatment (t 2). Cervical
      pain was evaluated at t 2 using a visual analogue scale (VAS). RESULTS: The TLSO
      was worn for an average of 4.6 years. Mean CSA, TSA and LSA were significantly
      lower at t 2 than at t 0: 0 +/- 2.5 degrees  vs. 9.4 +/- 2.3 degrees , 24.1 +/-
      2.6 degrees  vs. 29.3 +/- 2.4 degrees  and 5 +/- 1.9 degrees  vs. 44.2 +/- 2.5
      degrees , respectively (p < 0.05). CSA and TSA showed moderate-good correlation
      (r = 0.57). CSA was normolordotic in 1/38 patients at t 2 compared to 18/38 at t
      0 (p < 0.05). MC did not progress during treatment (p > 0.8). VAS score was 0 in
      all patients. CONCLUSIONS: The TLSO can control progression of the deformity in
      the frontal plane, but it influences CSA, TSA and LSA. In particular, it
      decreases cervical spine lordosis, with reduction maintained 1 year after the end
      of treatment. Numerical differences, although statistically significant, were not
      clinically relevant.

PMID- 27864685
TI  - Regulation of autophagy by Ca2.
AB  - Autophagy is an evolutionarily conserved lysosomal catabolic process used as an
      internal engine in response to nutrient starvation or metabolic stress. A number
      of protein complexes and an intricate network of stress signaling cascades
      impinge on the regulation of autophagy; the mammalian target of rapamycin serves
      as a canonical player. Ca2+, as a major intracellular second messenger, regulates
      multiple physiological and pathological functions. Although significant
      information is already well-established about the role of Ca2+ in apoptosis, its
      role in autophagy has been recently determined and is poorly understood.
      Intracellular Ca2+ positively and negatively affects autophagy. In this review,
      evidence for both views and the interplay of Ca2+ between autophagy and apoptosis
      induction are discussed. The available data revealed the bidirectional role of
      Ca2+ in the regulation of autophagy. Moreover, the data also indicated that this
      role probably depends on the context of time, space, Ca2+ source, and cell state,
      thus either preventing or enhancing autophagy.

PMID- 27864686
TI  - Zoledronic Acid (Reclast(r), Aclasta(r)): A Review in Osteoporosis.
AB  - Zoledronic acid (Reclast(r), Aclasta(r)) is an intravenous, highly potent
      aminobisphosphonate approved worldwide, including in the USA, EU and Japan for
      use in patients with primary or secondary osteoporosis or low bone mass (approved
      indications vary between countries). Its high affinity to and long half-life in
      bone, and long duration of action, allow for once-yearly administration, which
      has the potential to improve adherence to therapy. Zoledronic acid once yearly
      for up to 3 years improved bone mineral density (BMD) at several skeletal sites,
      reduced fracture risk and bone turnover, and/or preserved bone structure and mass
      relative to placebo in clinical studies in patients with primary or secondary
      osteoporosis. While additional benefits were seen when treatment was continued
      for up to 6 years, as evidenced by a reduced risk of vertebral fractures and
      higher BMD relative to 3 years' therapy, there was minimal advantage of treatment
      beyond 6 years. Therefore, in patients with low fracture risk, treatment
      discontinuation should be considered after approximately 5 years' therapy.
      Zoledronic acid administered annually or once in 2 years was also effective in
      preventing bone loss in patients with low bone mass. Zoledronic acid was
      generally well tolerated, with the most common adverse events (AEs) being
      transient, mild-to-moderate post-infusion symptoms, which decreased with
      subsequent infusions. To conclude, zoledronic acid once yearly is an effective
      and generally well tolerated treatment option for patients with osteoporosis.

PMID- 27864684
TI  - Network mechanisms of hippocampal laterality, place coding, and goal-directed
      navigation.
AB  - The hippocampus and associated structures are responsible for episodic memory in
      humans. In rodents, the most prominent behavioral correlate of hippocampal neural
      activity is place coding, which is thought to underlie spatial navigation. While
      episodic memory is considered to be unique to humans in a restricted context, it
      has been proposed that the same neural circuitry and algorithms that enable
      spatial coding and navigation also support episodic memory. Here we review the
      recent progress in neural circuit mechanisms of hippocampal activity by
      introducing several topics: (1) cooperation and specialization of the bilateral
      hippocampi, (2) the role of synaptic plasticity in gamma phase-locking of spikes
      and place cell formation, (3) impaired goal-related activity and oscillations in
      a mouse model of mental disorders, and (4) a prefrontal-thalamo-hippocampal
      circuit for goal-directed spatial navigation.

PMID- 27864687
TI  - Omega-3 fatty acid EPA improves regenerative capacity of mouse skeletal muscle
      cells exposed to saturated fat and inflammation.
AB  - Sarcopenic obesity is characterised by high fat mass, low muscle mass and an
      elevated inflammatory environmental milieu. We therefore investigated the effects
      of elevated inflammatory cytokine TNF-alpha (aging/obesity) and saturated fatty
      acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of
      EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity
      activities. In the present study we show that palmitate was lipotoxic, inducing
      high levels of cell death and blocking myotube formation. Cell death under these
      conditions was associated with increased caspase activity, suppression of
      differentiation, reductions in both creatine kinase activity and gene expression
      of myogenic factors; IGF-II, IGFBP-5, MyoD and myogenin. However, inhibition of
      caspase activity via administration of Z-VDVAD-FMK (caspase-2), Z-DEVD-FMK
      (caspase-3) and ZIETD-KMK (caspase 8) was without effect on cell death. By
      contrast, lipotoxicity associated with elevated palmitate was reduced with the
      MEK inhibitor PD98059, indicating palmitate induced cell death was MAPK mediated.
      These lipotoxic conditions were further exacerbated in the presence of
      inflammation via TNF-alpha co-administration. Addition of EPA under cytotoxic
      stress (TNF-alpha) was shown to partially rescue differentiation with enhanced
      myotube formation being associated with increased MyoD, myogenin, IGF-II and
      IGFBP-5 expression. EPA had little impact on the cell death phenotype observed in
      lipotoxic conditions but did show benefit in restoring differentiation under
      lipotoxic plus cytotoxic conditions. Under these conditions Id3 (inhibitor of
      differentiation) gene expression was inversely linked with survival rates,
      potentially indicating a novel role of EPA and Id3 in the regulation of apoptosis
      in lipotoxic/cytotoxic conditions. Additionally, signalling studies indicated the
      combination of lipo- and cyto-toxic effects on the muscle cells acted through
      ceramide, JNK and MAPK pathways and blocking these pathways using PD98059 (MEK
      inhibitor) and Fumonisin B1 (ceramide inhibitor) significantly reduced levels of
      cell death. These findings highlight novel pathways associated with in vitro
      models of lipotoxicity (palmitate-mediated) and cytotoxicity (inflammatory
      cytokine mediated) in the potential targeting of molecular modulators of
      sarcopenic obesity.

PMID- 27864688
TI  - Detection of mutations in the BRAF gene in patients with KIT and PDGFRA wild-type
      gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are characterized by mutations in exons
      9, 11, 13, and 17 of KIT or exons 12, 14, and 18 of PDGFRA gene. However,
      approximately 10 to 15 % of GISTs lack the mutations in KIT and PDGFRA, and these
      are referred to as wild-type GISTs which are less sensitive to tyrosine-kinase
      inhibitors. The aim of this study was to detect BRAF mutations in patients with
      wild-type GISTs. We applied a sensitive allele-specific PCR, which was optimized
      using the V600E mutation-harboring cell line RKO, followed by verification of the
      results by dideoxy sequencing. We selected 149 GIST patients without detectable
      mutations in KIT and PDGFRA genes from the Slovak national GIST register and
      analyzed biopsy specimens for the presence of BRAF mutations in exon 15. We
      identified nine patients with the V600E mutation. The BRAF-driven GISTs were
      primary gastric (n = 3), small intestinal (n = 3), colon (n = 1), and of
      uncertain origin (n = 1). We also included a liver metastasis of a patient with a
      simultaneous KIT exon 11-mutated intra-abdominal metastasis. We conclude that
      genome analysis of wild-type GISTs for mutations should include the BRAF gene, as
      its mutation status contributes to understanding of pathogenesis and might be
      important for decisions on therapy.

PMID- 27864689
TI  - Epstein-Barr virus infection and gene promoter hypermethylation in rheumatoid
      arthritis patients with methotrexate-associated B cell lymphoproliferative
      disorders.
AB  - We analyzed CpG-island hypermethylation status in 12 genes of paraffin-embedded
      tissues from 38 rheumatoid arthritis (RA) patients with methotrexate (MTX)
      associated large B cell lymphoproliferative disorder (BLPD), 11 RA patients with
      non-MTX-associated BLPD (non-MTX-BLPD), 22 controls with diffuse large B cell
      lymphoma (DLBCL), and 10 controls with Epstein-Barr virus (EBV)+ DLBCL. Among
      them, tumor cells from EBV+ MTX-BLPD patients and control EBV+ DLBCL patients had
      significantly lower median incidence of CpG island methylator phenotype (CIMP)
      than those from non-MTX-BLPD and control DLBCL groups (2.3 and 1.7 vs. 4.3 and
      4.4; P < 0.01 for each). In the MTX-BLPD group, EBV+ patients showed lower median
      CIMP than EBV- patients (2.3 vs. 3.2); they also had significantly lower
      hypermethylation incidence in four apoptosis-related genes, especially death
      associated protein kinase (14 vs. 55 %), higher incidence of massive tumor
      necrosis (86 vs. 27 %), and lower BCL2 protein expression (19 vs. 86 %) than did
      the control DLBCL group (P < 0.01 for all). In all clinical stages, EBV+ MTX-BLPD
      patients had better prognoses than the EBV- MTX-BLPD (P = 0.011), non-MTX-BLPD (P
      = 0.002), and control DLBCL groups (P = 0.015). MTX-BLPD patients without
      hypermethylated RAS-associated domain family-1A (RASSF1A) or O 6 -methyl guanine
      DNA methyltransferase (MGMT) had significantly better prognosis than those with
      hypermethylation of those genes (P = 0.033). We conclude that in RA patients with
      MTX-BLPD, EBV infection is associated with a lower incidence of CIMP, apoptosis
      related gene hypermethylation, and BCL2 expression, which can induce tumor
      regression by MTX withdrawal and lead to better prognoses.

PMID- 27864690
TI  - Infrequent mismatch repair protein loss in gallbladder cancer patients in Japan.

PMID- 27864691
TI  - Characterization of TG2 and TG1-TG2 double knock-out mouse epidermis.
AB  - Transglutaminases (TGs) are a family of enzymes that catalyse the formation of
      isopeptide bonds between the gamma-carboxamide groups of glutamine residues and
      the epsilon-amino groups of lysine residues leading to cross-linking reactions
      among proteins. Four members, TG1, TG2, TG3, and TG5, of the nine mammalian
      enzymes are expressed in the skin. TG1, TG3 and TG5 crosslinking properties are
      fundamental for cornified envelope assembly. In contrast, the role of TG2 in
      keratinization has never been studied at biochemical level in vivo. In this
      study, taking advantage of the TG2 knock-out (KO) and TG1 heterozygous mice, we
      generated and characterized the epidermis of TG1-TG2 double knock-out (DKO) mice.
      We performed morphological analysis of the epidermis and evaluation of the
      expression of differentiation markers. In addition, we performed analysis of the
      amino acid composition from isolated corneocytes. We found a significant change
      in amino acid composition in TG1KO cornified cell envelopes (CEs) while TG2KO
      amino acid composition was similar to wild-type CEs. Our results confirm a key
      role of TG1 in skin differentiation and CE assembly and demonstrate that TG2 is
      not essential for CE assembly and skin formation.

PMID- 27864692
TI  - Transglutaminase 2 is involved in amyloid-beta1-42-induced pro-inflammatory
      activation via AP1/JNK signalling pathways in THP-1 monocytes.
AB  - Deposition of amyloid-beta (Abeta) peptides has been shown to induce the release
      of inflammatory factors by activated microglia and brain infiltrating
      monocytes/macrophages. Interestingly, the enzyme transglutaminase 2 (TG2) has
      been shown to play a key role in neuroinflammation and regulation of
      transcription factors involved in immunomodulation. In this study, we aimed to
      better elucidate the mechanisms underlying TG2 involvement in the pro
      inflammatory signaling pathway activated by fibrillar Abeta1-42 in THP-1
      monocytes. Cell exposure for 24 h to 500 nM Abeta1-42, induced the up-regulation
      of CD14, CD16, and TG2, suggesting THP-1 cell functional activation. Abeta1-42
      also increased the production of reactive oxygen species, that was reduced by the
      pre-incubation with genistein (25 ug/ml), a soy isoflavone with antioxidant
      properties. Moreover, IL-1beta and IL-6 mRNA transcript and protein levels were
      eightfold increased in Abeta1-42-treated THP-1 monocytes. Interestingly, these
      effects were significantly reduced by R283 (~45%), a specific inhibitor of TG
      activity, and genistein (~40%). Abeta1-42 induced the activation of p54/p46 JNK,
      as well as ERK 1/2 at a lower extent. The inactivation of ERK1/2 signalling
      pathway, but not JNK, by either genistein or U0126, a MEK1/2 inhibitor, was not
      able to blunt Abeta1-42-induced TG2 up-regulation, that, instead, was
      significantly reduced by R283. Abeta1-42 also induced AP-1 activation that was
      not significantly affected by genistein or U0126, while was strongly reduced by
      R283. Our preliminary findings first suggest that TG2 up-regulation is involved
      in the pro-inflammatory activation of THP-1 monocytes induced by Abeta1-42 via
      AP1/JNK signalling pathways.

PMID- 27864693
TI  - Synthesis and biological evaluation of a novel Amadori compound.
AB  - Here, we report the synthesis, purification, ESI MS and NMR characterization, as
      well as the SEM analysis of a fructosyl thiophenyl-substituted triazolyl-thione L
      alanine (denominated Fru-L-TTA). This novel fructosyl derivative was obtained by
      solution synthesis using the Amadori reaction, in analogy to other natural
      fructosyl-amino acids, and fully characterized. In particular, we report an
      accurate NMR/MS/SEM characterization of Fru-L-TTA alongside some biological
      properties, and investigated to compare the properties of the artificial
      derivative of this work with the natural counterparts. In particular, Fru-L-TTA
      shares with natural fructosyl-amino acids the possibility to inhibit the colony
      formation of prostate cancer cells and additionally decreases their migration.

PMID- 27864695
TI  - Adjuvant Chemotherapy Improves Overall Survival of Rectal Cancer Patients Treated
      with Neoadjuvant Chemoradiotherapy Regardless of Pathologic Nodal Status.
AB  - BACKGROUND: After neoadjuvant chemoradiotherapy for rectal cancer, the
      interpretation of surgical pathology poses difficulties in deciding the need for
      adjuvant chemotherapy (AC). The aim of this study was to determine whether there
      is a survival benefit to providing AC in patients with node-negative disease on
      surgical pathology. METHODS: Patients with clinical stage II and III rectal
      adenocarcinoma who received neoadjuvant chemoradiation and definitive surgical
      resection from 2006 to 2012 were identified in the National Cancer Data Base.
      Patients were stratified by both receipt of AC and nodal status on surgical
      pathology. Propensity score matching was used to form two cohorts (AC vs. no AC)
      with otherwise balanced characteristics. Overall survival was compared by Kaplan
      Meier analysis, and multivariable survival analysis was performed by a Weibull
      model. RESULTS: After propensity score matching, 4172 patients who received
      adjuvant therapy (2645 node negative and 1527 node positive) and 4172 patients
      who did not receive adjuvant therapy (3063 node negative and 1109 node positive)
      were identified. Among patients with either node-negative or node-positive
      disease, the use of AC was associated with a significant improvement in overall
      survival. These results were also observed after using a multivariable survival
      model to control for clinical stage as well as patient- and facility-related
      characteristics. CONCLUSIONS: In both patients with node-negative and node
      positive disease on surgical pathology, the use of AC is associated with a
      survival benefit. In the absence of contraindications, AC should continue to be
      routinely recommended to patients after neoadjuvant chemoradiotherapy for locally
      advanced rectal cancers.

PMID- 27864694
TI  - The Effect on Surgical Complications of Bevacizumab Added to Neoadjuvant
      Chemotherapy for Breast Cancer: NRG Oncology/NSABP Protocol B-40.
AB  - BACKGROUND: NRG Oncology/NSABP trial B-40 tested the impact of adding bevacizumab
      (bev) to neoadjuvant chemotherapy for operable breast cancer. Secondary endpoints
      included rates of surgical complications after surgery in patients who did or did
      not receive bev. METHODS: A total of 1206 women with HER2-negative operable
      breast cancer were randomly assigned to receive one of three different docetaxel
      plus-anthracycline-based regimens, without or with bev (15 mg/kg every 3 weeks)
      for the first 6 of 8 cycles and for 10 doses postoperatively. Surgical
      complications were assessed from date of surgery through 24 months following
      study entry. RESULTS: Early surgical complications were significantly more
      frequent in the bev group (25.4 vs. 18.9%; trend test p = 0.008), but most were
      grade 1-2. Early noninfectious wound dehiscences were infrequent and not
      significantly different (5.4 vs. 3.1%; trend test p = 0.15). Long-term
      noninfectious wound complications were significantly higher for patients
      receiving bev (11.8 vs. 5.1%; trend test p = 0.0007), but the incidence of grade
      >=3 wound dehiscence was low in both groups (<1%). Among 193 patients undergoing
      expander or implant reconstructions, 19 (19.6%) of 97 in the bev-receiving group
      versus 10 (10.4%) of 96 in the non-bev group had grade >=3 complications
      (Pearson, p = 0.11). CONCLUSIONS: Overall, adding bev increased surgical
      complications, but most serious complications were not significantly increased.
      In particular, the need for surgical intervention in patients undergoing breast
      reconstruction with prosthetic implants was higher with bev but was not
      statistically significantly different. With precautions, bev can be used safely
      perioperatively in patients undergoing surgery for breast cancer.

PMID- 27864696
TI  - Generation and differentiation of induced pluripotent stem cells reveal
      ankylosing spondylitis risk gene expression in bone progenitors.
AB  - Axial spondyloarthritis (axSpA), which encompasses ankylosing spondylitis, is a
      complex genetic disease. Aberrant bone formation is a key feature of pathogenesis
      that can lead to ankylosis of the spine. Our objective is to determine, whether
      genes whose variants confer susceptibility to AS are expressed in bone
      progenitors like mesenchymal stem cells (MSCs). Since MSCs from bone marrow is
      difficult to obtain, we first examined, whether MSCs can be derived from induced
      pluripotent stem cells (iPSCs). Dermal fibroblasts of two axSpA patients and one
      healthy control were reprogrammed into iPSCs using a Sendai virus vector encoding
      pluripotency genes. Pluripotency of iPSCs was examined by embryoid body formation
      and by testing for stem cell specific gene and protein expression using RT-PCR
      and immuno fluorescence. iPSCs were differentiated into MSCs by a TGFbeta
      inhibitor. MSCs were characterized by flow cytometry using lineage specific
      antibodies and by their capacity to develop into chondrocytes, adipocytes, and
      osteoblasts in lineage-specific medium. RNA-seq was applied to determine genome
      wide gene expression patterns in MSCs, iPSCs, and blood. We show for the first
      time, that expression levels of several AS susceptibility genes (EDIL3, ANO6,
      HAPLN1, ANTXR2) involved in bone formation are significantly elevated in MSCs (2
      15-fold; p <= 0.05) compared to blood or iPSCs and demonstrate that iPSC-derived
      MSCs can be differentiated into osteoblasts, chondrocytes, and adipocytes. We
      conclude, MSCs generated from patient fibroblast-derived iPSC lines are useful
      tools for studying functional genomics of risk genes associated with bone
      formation in AS pathogenesis.

PMID- 27864697
TI  - Characteristics of primary Sjogren's syndrome patients with IgG4 positive plasma
      cells infiltration in the labial salivary glands.
AB  - The purpose of this study was to investigate the characteristics of primary
      Sjogren's syndrome (pSS) patients with IgG4 positive (IgG4+) plasma cell
      infiltration in labial salivary glands (LSGs). Paraffin sections of LSGs from 336
      pSS patients were stained with IgG4 and IgG monoclonal antibodies. According to
      the infiltration of IgG4+ plasma cells, patients were divided and clinical and
      serological characteristics were analyzed and compared. Based on the infiltration
      of IgG4+ plasma cells in the LSGs, patients were divided into three subgroups,
      low IgG4, moderate IgG4, and high IgG4 groups. A negative association between the
      number of infiltrated IgG4+ plasma cells and the disease characteristics was
      observed. We found that the higher the IgG4+ expression in plasma cells, the
      lower the positive rates of serum anti-SSA antibodies, anti-SSB antibodies,
      antinuclear antibodies (ANA), and rheumatoid factor (RF). Besides, patients from
      the high IgG4 group had the highest frequency of interstitial lung disease (ILD,
      30.6%) and tubulointerstitial nephritis (TIN, 13.9%), but the lowest frequency of
      leucopenia (13.9%), thrombocytopenia (11.1%), and abnormal thyroidal function
      (0%). PSS patients with different IgG4+ plasma cells infiltration in the LSGs had
      distinctive clinical and laboratory characteristics. It may help us to further
      understand the role of IgG4+ plasma cells in pSS.

PMID- 27864698
TI  - BLK pathway-associated rs13277113 GA genotype is more frequent in SLE patients
      and associated with low gene expression and increased flares.
AB  - We aimed to evaluate the relationship between some important genetic variations
      and expressions of these genes in our SLE population. We also determined their
      association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and
      105 healthy controls (98 F, 7 M) were included in the study. rs13277113,
      rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene
      expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk,
      ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for
      rs13277113 polymorphism was more frequent in patients with SLE when compared to
      that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were
      similar in SLE patients and controls. In the SLE group, the heterozygous genotype
      for rs13277113 was significantly less frequent in active SLE patients (58.8 vs.
      26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were
      significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340)
      genotypes (66.7 vs. 35.2%) than those in other genotypes (p values <0.01). The
      relative expression of Blk gene was significantly decreased in the SLE group as
      compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions
      of Blk and ZAP70 were significantly lower in SLE patients who had flares
      according to the SELENA-SLEDAI flare index when compared to those in others (p
      values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic
      pattern (rs13277113) in our SLE patients compared to that in controls; and it was
      associated with disease flares. Blk gene expression in SLE was lower, especially
      in relapsing patients.

PMID- 27864699
TI  - An Experimental Framework for Generating Evolvable Chemical Systems in the
      Laboratory.
AB  - Most experimental work on the origin of life has focused on either characterizing
      the chemical synthesis of particular biochemicals and their precursors or on
      designing simple chemical systems that manifest life-like properties such as self
      propagation or adaptive evolution. Here we propose a new class of experiments,
      analogous to artificial ecosystem selection, where we select for spontaneously
      forming self-propagating chemical assemblages in the lab and then seek evidence
      of a response to that selection as a key indicator that life-like chemical
      systems have arisen. Since surfaces and surface metabolism likely played an
      important role in the origin of life, a key experimental challenge is to find
      conditions that foster nucleation and spread of chemical consortia on surfaces.
      We propose high-throughput screening of a diverse set of conditions in order to
      identify combinations of "food," energy sources, and mineral surfaces that foster
      the emergence of surface-associated chemical consortia that are capable of
      adaptive evolution. Identification of such systems would greatly advance our
      understanding of the emergence of self-propagating entities and the onset of
      adaptive evolution during the origin of life.

PMID- 27864700
TI  - A highly Sensitive Turn-on Fluorescent Sensor for Ba2+ Based on G-Quadruplexes.
AB  - A G-quadruplex-based fluorescent biosensor for highly sensitive detection of
      barium ion (Ba2+) was constructed for the first time. In the absence of Ba2+, the
      G-quadruplex-specific fluorescence ligand N-methyl mesoporphyrin IX (NMM)
      remained weakly fluorescent when coexisted with a single-stranded G-quadruplex
      sequence AGRO100. Upon addition of Ba2+, AGRO100 was folded into G-quadruplex
      structures with the aid of Ba2+, which bound with NMM by stacking forces and
      significantly enhanced its fluorescence. The maximum fluorescence intensity of
      NMM was increased by ca. 22-fold in response to 1 MUM Ba2+. This simple method
      exhibites a good linear relationship in the range of 0-600 nM with the detection
      limit of 4 nM. The detection method is turn-on, fast, economic, high in signal-to
      noise ratio and free of participation of toxic organic solvents, demonstrating
      its great potential for on-site and real-time Ba2+ detection.

PMID- 27864701
TI  - Atomistic Engineering of Chemiluminogens: Synthesis, Properties and
      Polymerization of 2,3-Dihydro-Pyrrolo[3,4-d]Pyridazine-1,4-Dione Scaffolds.
AB  - Two chemiluminescent compounds containing 2,5-di(thien-2-yl)pyrrole and
      pyridazine units, namely 5,7-di(thiophen-2-yl)-2,3-dihydro-1H-pyrrolo[3,4
      d]pyridazine-1,4(6H)-dione (5) and 6-phenyl-5,7-di(thiophen-2-yl)-2,3-dihydro-1H
      pyrrolo[3,4-d]pyridazine-1,4(6H)-dione (6), were successfully synthesized and
      electrochemically polymerized. The compounds have chemiluminescent properties and
      glow in the presence of hydrogen peroxide in basic medium. The intensity of the
      glow can be increased dramatically by using Fe3+ ions, hemin (1.0 ppm) or blood
      samples (1.0 ppm) as catalyst. The compounds 5 and 6 have one well-defined
      irreversible oxidation peak at 1.08 V and 1.33 V vs Ag/AgCl, respectively.
      Electrochemical polymerization of both 5 and 6 were carried out successfully by
      repeating potential scanning in the presence of BF3. Et2O in an electrolyte
      solution of 0.1 M LiClO4 dissolved in acetonitrile. The electronic band gaps (Eg)
      of the polymers P5 and P6 were found to be 2.02 eV and 2.16 eV, respectively. On
      the other hand, the corresponding polymers are electroactive and exhibited
      electrochromic features. Graphical Abstract ?.

PMID- 27864702
TI  - Selective Spectrofluorimetric Method with Enhanced Sensitivity for Determination
      of Silodosine in Dosage Form and Human Plasma. Application to Stability Studies
      and Content Uniformity Testing.
AB  - A novel, sensitive and selective spectrofluorimetric method has been developed
      and validated for determination of silodosine (SLD) in its dosage form and human
      plasma. The method is based on nucleophilic substitution reaction of SLD with 5
      (dimethylamino) naphthalene-1-sulfonyl chloride (dansyl chloride) in presence of
      5.0 * 10-4 M sodium carbonate (pH 10.50) to yield a highly fluorescent derivative
      that was measured at 435 nm after excitation at 347 nm. The different
      experimental parameters affecting the development and stability of the reaction
      product were carefully studied and optimized. The fluorescence-concentration plot
      was rectilinear over the range 30.0-200.0 ng ml-1, with a correlation coefficient
      of 0.9979. The limits of detection (LOD) and quantification (LOQ) were found to
      be 5.44 and 16.47 ng ml-1, respectively. The proposed method was validated
      according to ICH guidelines, and successfully applied to the assay of commercial
      capsules as well as content uniformity testing. The high sensitivity of the
      proposed method allowed its successful application to the analysis of SLD in
      spiked human plasma with % recovery of 92.88 +/- 1.05-100.73 +/- 0.75%, (n = 6).
      The application of the proposed method was further extended to stability studies
      of SLD after exposure to different forced degradation conditions, such as acidic,
      alkaline and oxidative conditions, according to ICH guidelines, where this work
      describe the first attempt for selective spectrofluorimetric determination of
      silodosine in plasma and in the presence of its oxidative degradation.

PMID- 27864703
TI  - Longitudinal experience with WHO Grade III (anaplastic) meningiomas at a single
      institution.
AB  - To retrospectively analyze and assess the outcomes and prognostic factors in
      patients with anaplastic meningioma (AM) (WHO Grade III). Clinical data and
      outcome [overall (OS) and progression-free (PFS) survival] from 18 patients with
      Grade III meningioma (AM, based on World Health Organization 2016 definition)
      initially treated between March 2000 and June 2015 were analyzed. Eleven patients
      (61%) were male, median age at diagnosis was 63 (range 48-86), and 55% (10/18
      patients) had good performance status (KPS >= 80). Eight patients (45%) had lower
      grade disease (Grade I-n = 2; Grade II-n = 6) prior to being upgraded to AM. Ten
      patients had fractionated radiation after primary surgery, eight patients had
      salvage fractionated RT, stereotactic radiosurgery (SRS) boost along with primary
      RT in 1 patient, and salvage SRS to 18 separate areas in 14 patients. Salvage
      chemotherapy was mainly considered in third or fourth recurrences. 13 (72%)
      patients recurred and 10 (56%) have died. Median PFS was 14.5 months (95% CI 6.9
      22.2). The 5-year survival rate was 40 +/- 15% and median OS was 55.8 months (95%
      CI 27.7-80.3). Of all factors examined, only Karnofsky performance status (KPS)
      affected outcome (PFS p = 0.0003; OS p = 0.0003). With median OS of 55 months
      (4.6 years) our results are consistent with existing reports of the poor outcomes
      for AM patients. From the available data, surgical resection followed by RT and
      salvage radiosurgery and/or chemotherapy can lead to extended survival; however
      the benefit may decrease with successive treatments.

PMID- 27864704
TI  - A clinicopathologic study of extraventricular neurocytoma.
AB  - In 2007, extraventricular neurocytoma was classified as a separate entity among
      glioneuronal tumors. However, extraventricular neurocytoma is not fully
      understood and may be misdiagnosed. Here, we describe the clinical and
      pathological features, prognoses, and treatments of 13 extraventricular
      neurocytoma cases, and compare their immunophenotypes with those of
      oligodendroglioma, diffuse astrocytoma, and ependymoma. Six typical and 7
      atypical cases comprised the 13 extraventricular neurocytoma cases. Histological
      features included oligodendroglioma-like perinuclear halo, neuropil-like matrix,
      ganglion or ganglioid cells, perivascular pseudorosettes, vessel hyalinization,
      calcifications, and myxoid degeneration. Atypical histological features included
      increased mitotic figures, focal necrosis, endothelial cell proliferation, and/or
      a Ki-67 index of >2%. All lesions expressed synaptophysin and microtubule
      associated protein-2, which distinguished them from other similar tumors. Two
      patients with atypical extraventricular neurocytoma had tumor recurrence, one of
      whom had cerebrospinal fluid dissemination, suggesting that atypical histological
      features might represent adverse prognostic factors. In conclusion, the present
      study identified morphological and immunohistochemical features that would aid
      the differential diagnosis of extraventricular neurocytoma. In addition,
      radiotherapy with subtotal resection could be considered an effective treatment
      for extraventricular neurocytoma, but because a pediatric patient died of
      intracranial hemorrhage during radiotherapy, radiotherapy-related side effects
      should be considered, especially when treating children. Additional cases with
      long-term follow-up are needed to develop optimal management protocols for
      extraventricular neurocytoma.

PMID- 27864705
TI  - The clinical and financial impact of a pediatric surgical neuro-oncology clinical
      trial.
AB  - Pediatric surgical trials are rare and the impact of such trials on the
      institutions in which they are conducted is unknown. The purpose of this study
      was to analyze the clinical and financial impact of The Re-MATCH trial, a Phase I
      clinical trial requiring the biopsy or resection of recurrent medulloblastoma or
      PNET for enrollment. Inpatient financial and clinical volume information was
      collected during the 3 years of trial enrollment and the years preceding and
      following it. The primary endpoints were the difference in direct contribution
      margin (DCM), or net gain, of study and non-study patients and the difference in
      surgical volume during the study and non-study periods. The trial enrolled 18
      patients; 15 had surgery at the sponsor institution and three had surgery at
      their home institution, then transferred tumor material to the sponsor
      institution. There were no differences between the two groups for potentially
      confounding variables such as neurosurgical procedure work relative value units
      (P = 0.13) or insurance provider (P = 0.26). There was no difference between the
      inpatient DCM per case for the institution for non-study patients (mean +/- SD,
      $9039 +/- $28,549) and study patients ($14,332 +/- $20,231) (P = 0.4819). During
      the non-study period, there were a mean of 2.78 +/- 1.65 pediatric brain tumor
      resections per month compared to 3.34 +/- 1.66 cases per month during the study
      period, a 17% increase. When the 15 study patients were excluded, there were 2.97
      +/- 1.64 cases per month, a 7% increase. However, this increase in total case
      volume including study and non-study patients was not significant (P = 0.121).
      Phase I investigator-initiated surgically-based clinical trials may increase
      institutional surgical volume without imposing a financial burden. Finances are
      unlikely to be a barrier for researchers negotiating for resources to conduct
      such trials.

PMID- 27864706
TI  - Influence of insurance status and income in anaplastic astrocytoma: an analysis
      of 4325 patients.
AB  - To determine the impact of insurance status and income for anaplastic astrocytoma
      (AA). Data were extracted from the National Cancer Data Base. Chi square test,
      Kaplan-Meier method, and Cox regression models were employed in SPSS 22.0
      (Armonk, NY: IBM Corp.) for data analyses. 4325 patients with AA diagnosed from
      2004 to 2013 were identified. 2781 (64.3%) had private insurance, 925 (21.4%)
      Medicare, 396 (9.2%) Medicaid, and 223 (5.2%) were uninsured. Those uninsured
      were more likely to be Black or Hispanic versus White or Asian (p < 0.001), have
      lower median income (p < 0.001), less educated (p < 0.001), and not receive
      adjuvant chemoradiation (p < 0.001). 1651 (38.2%) had income >=$63,000, 1204
      (27.8%) $48,000-$62,999, 889 (20.5%) $38,000-$47,999, and 581 (13.4%) had income
      <$38,000. Those with lower income were more likely to be Black or Hispanic versus
      White or Asian (p < 0.001), uninsured (p < 0.001), reside in a rural area (p <
      0.001), less educated (p < 0.001), and not receive adjuvant chemoradiation (p <
      0.001). Those with private insurance had significantly higher overall survival
      (OS) than those uninsured, on Medicaid, or on Medicare (p < 0.001). Those with
      income >=$63,000 had significantly higher OS than those with lower income (p <
      0.001). On multivariate analysis, age, insurance status, income, and adjuvant
      therapy were independent prognostic factors for OS. Being uninsured and having
      income <$38,000 were independent prognostic factors for worse OS in AA. Further
      investigations are warranted to help determine ways to ensure adequate medical
      care for those who may be socially disadvantaged so that outcome can be maximized
      for all patients regardless of socioeconomic status.

PMID- 27864707
TI  - Impact of operative length on post-operative complications in meningioma surgery:
      a NSQIP analysis.
AB  - Many studies have implicated operative length as a predictor of post-operative
      complications, including venous thromboembolism [deep vein thrombosis (DVT) and
      pulmonary embolism (PE)]. We analyzed the American College of Surgeons (ACS)
      National Surgical Quality Improvement Program (NSQIP) database from 2006 to 2014,
      to evaluate whether length of operation had a statistically significant effect on
      post-operative complications in patients undergoing surgical resection of
      meningioma. Patients were included for this study if they had a post-operative
      diagnosis of meningioma. Patient demographics, pre-operative comorbidities, and
      post-operative 30-day complications were analyzed. Of 3743 patients undergoing
      craniotomy for meningioma, 13.6 % experienced any complication. The most common
      complications and their median time to occurrence were urinary tract infection
      (2.6 %) at 10 days postoperatively (IQR 7-15), unplanned intubation (2.5 %) at 3
      days (IQR 1-7), failure to wean from ventilator (2.4 %) at 2.0 days (IQR 2-4),
      and DVT (2.4 %) at 6 days (IQR 11-19). Postoperatively, 3.6 % developed VTE; 2.4
      % developed DVT and 1.7 % developed PE. Multivariable analysis identified older
      age (third and upper quartile), obesity, preoperative ventilator dependence,
      preoperative steroid use, anemia, and longer operative time as significant risk
      factors for VTE. Separate multivariable logistic regression models demonstrated
      longer operative time as a significant risk factor for VTE, all complications,
      major complications, and minor complications. Meningioma resection is associated
      with various post-operative complications that increase patient morbidity and
      mortality risk. this large, multi-institutional patient sample, longer operative
      length was associated with increased risk for postoperative venous
      thromboembolisms, as well as major and minor complications.

PMID- 27864710
TI  - Regulation of sporopollenin synthesis for pollen wall formation in plant.

PMID- 27864711
TI  - Mesenchymal stem cells-derived exosomal microRNAs contribute to wound
      inflammation.
AB  - Clinical and experimental studies have highlighted the significance of
      inflammation in coordinating wound repair and regeneration. However, it remains
      challenging to control the inflammatory response and tolerance at systemic levels
      without causing toxicity to injured tissues. Mesenchymal stem cells (MSCs)
      possess potent immunomodulatory properties and facilitate tissue repair by
      releasing exosomes, which generate a suitable microenvironment for inflammatory
      resolution. Exosomes contain several effective bioactive molecules and act as a
      cell-cell communication vehicle to influence cellular activities in recipient
      cells. During this process, the horizontal transfer of exosomal microRNAs
      (miRNAs) to acceptor cells, where they regulate target gene expression, is of
      particular interest for understanding the basic biology of inflammation ablation,
      tissue homeostasis, and development of therapeutic approaches. In this review, we
      describe a signature of three specific miRNAs (miR-21, miR-146a, and miR-181)
      present in human umbilical cord MSC-derived exosomes (MSC-EXO) identified
      microarray chip analysis and focus on the inflammatory regulatory functions of
      these immune-related miRNAs. We also discuss the potential mechanisms
      contributing to the resolution of wound inflammation and tissue healing.

PMID- 27864712
TI  - Associations between serum lipids and breast cancer incidence and survival in the
      E3N prospective cohort study.
AB  - PURPOSE: Several mechanistic studies support a role of cholesterol or its
      metabolites in breast cancer etiology, but associations have been inconsistent in
      epidemiological studies. In observational studies, possible reverse causation
      must be accounted for using a prospective design. We investigated prospective
      associations between pre-diagnostic serum lipid concentrations [total cholesterol
      (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol,
      triglycerides], and both breast cancer risk and survival in the E3N cohort study.
      METHODS: Analyses were performed on 583 cases from the E3N prospective cohort
      diagnosed between 1994 and 2005, and 1,043 controls matched on date, age,
      recruitment center and menopausal status at blood collection. Odds ratios (OR)
      and 95% confidence intervals were estimated using conditional logistic
      regression. Risks of recurrence were estimated among cases using Cox proportional
      hazards model. Models were adjusted for lifestyle risk factors and mutually
      adjusted for lipid concentrations. Survival analyses were additionally adjusted
      for tumor characteristics. RESULTS: Overall, there was no association between any
      serum lipid and breast cancer risk or survival. In stratified analyses,
      statistically significant interaction was observed between TC and menopausal
      status (P interaction = 0.05) and between TC and waist circumference (P
      interaction = 0.03), although the ORs did not reach statistical significance in
      any of the strata. There was no statistically significant effect modification by
      BMI, time between blood donation and diagnosis or ER status. CONCLUSIONS: Our
      results suggest that serum lipids are not associated with breast cancer risk
      overall, but that menopausal status and waist circumference should be considered
      in further studies.

PMID- 27864708
TI  - Thyroid dysfunction and kidney disease: An update.
AB  - Thyroid hormones influence renal development, kidney hemodynamics, glomerular
      filtration rate and sodium and water homeostasis. Hypothyroidism and
      hyperthyroidism affect renal function by direct renal effects as well as systemic
      hemodynamic, metabolic and cardiovascular effects. Hypothyroidism has been
      associated with increased serum creatinine and decreased glomerular filtration
      rate. The reverse effects have been reported in thyrotoxicosis. Most of renal
      manifestations of thyroid dysfunction are reversible with treatment. Kidney
      disease may also cause thyroid dysfunction by several mechanisms. Nephrotic
      syndrome has been associated to changes in serum thyroid hormone concentrations.
      Different forms of glomerulonephritis and tubulointerstitial disease may be
      linked to thyroid derangements. A high prevalence of thyroid hormone alteration
      has been reported in acute kidney injury. Thyroid dysfunction is highly prevalent
      in chronic kidney disease patients. Subclinical hypothyroidism and low
      triiodothyronine syndrome are common features in patients with chronic kidney
      disease. Patients treated by both hemodialysis and peritoneal dialysis, and renal
      transplantation recipients, exhibit thyroid hormone alterations and thyroid
      disease with higher frequency than that found in the general population. Drugs
      used in the therapy of thyroid disease may lead to renal complications and,
      similarly, drugs used in kidney disorders may be associated to thyroid
      alterations. Lastly, low thyroid hormones, especially low triiodothyronine
      levels, in patients with chronic kidney disease have been related to a higher
      risk of cardiovascular disease and all-cause mortality. Interpretation of the
      interactions between thyroid and renal function is a challenge for clinicians
      involved in the treatment of patients with thyroid and kidney disease.

PMID- 27864713
TI  - A prospective randomized study for efficacy of an uncovered double bare metal
      stent compared to a single bare metal stent in malignant biliary obstruction.
AB  - BACKGROUND AND AIMS: A biliary self-expandable metal stent (SEMS) is commonly
      used to relieve malignant biliary obstruction. The aim of this study was to
      compare the efficacy of a conventional uncovered SEMS with that of a newly
      developed uncovered double bare metal stent in reducing the risk of stent
      occlusion caused by tumor ingrowth. PATIENTS AND METHODS: We performed a
      prospective, open-labeled, randomized trial in 71 patients at Severance Hospital,
      Yonsei University College of Medicine from June 2013 to June 2014. Patients with
      inoperable malignant biliary obstruction were included and randomized to receive
      an uncovered single bare metal stent (SBSs; S&G Biotech Inc.), an uncovered
      single bare metal stent (SBSt; Taewoong Medical), or an uncovered double bare
      metal stent (DBS; S&G Biotech Inc.). RESULTS: The mean age was 66.6 years (range,
      35-83), and 42 (59.2%) were male. The mean duration of stent patency was 212 days
      (+/-152) in the DBS group (n = 24) compared with 124 days (+/-98) in the SBSs
      group (n = 23; P = 0.022 for noninferiority) and 116 days (+/-79) in the SBSt
      group (n = 24; P = 0.010 for noninferiority). There were no differences in the
      incidences of early and delayed complications or migration. CONCLUSIONS: The
      newly developed DBS is noninferior to the conventional uncovered SEMSs on
      duration of stent patency and tumor ingrowth occurred less frequently in the DBS
      group. This might decrease the need for reintervention and offer a better quality
      of life. The trial is registered with Clinicaltrials.gov no: NCT01869894.

PMID- 27864714
TI  - Clinical features of postoperative anastomotic bleeding after gastrectomy and
      efficacy of endoscopic hemostasis: a case-control study.
AB  - BACKGROUND: Postoperative anastomotic bleeding (PAB) is relatively rare; however,
      it can be lethal if not treated immediately. The aim of our study was to
      investigate the clinical features of PAB and the efficacy of endoscopic
      hemostasis (EH) for PAB. METHODS: Between January 2004 and May 2013, 16,591
      patients underwent gastrectomy for gastric cancer at Asan Medical Center. Among
      them, 36 patients who experienced PAB within 2 months after the gastrectomy were
      enrolled as a case group. Each subject was matched at a ratio of 1:5 with
      randomly selected patients without bleeding during the same period (n = 180,
      control group). The clinical outcomes and risk factors for patients with PAB were
      compared with those of the control group, and the results of EH were evaluated
      retrospectively. RESULTS: The incidence of PAB was 0.22% (n = 36), and the median
      duration from gastrectomy to PAB was 34.5 h (interquartile range, 12.3-132.8 h).
      EH was attempted in 25 patients (69.4%); surgery was performed in 6 patients
      (16.7%); and conservative management was applied in 5 patients (13.9%). PAB
      related death occurred in three patients (8.3%; one in each treatment modality).
      Among 25 patients with primary EH, 16 were treated successfully (64%) and
      hemoclip was the most commonly used endoscopic tool (52%). In the multivariate
      analysis, the type of gastrectomy was found to be a risk factor for PAB (odds
      ratio 3.448, 95% confidence interval, 1.138-10.448, p = .029). CONCLUSIONS:
      Although PAB is an infrequent and potentially life-threatening complication,
      endoscopy can be considered as a useful method to avoid additional surgery in
      properly selected patients.

PMID- 27864715
TI  - Laparoscopic antireflux surgery increases health-related quality of life in
      children with GERD.
AB  - INTRODUCTION: Improving health-related quality of life (HRQoL) is increasingly
      recognized as an essential part of patient care outcome. Little is known about
      the effect of laparoscopic antireflux surgery (LARS) on the HRQoL in the
      pediatric patients. The aims of this study were to evaluate the effect of LARS on
      HRQoL in children with gastroesophageal reflux disease (GERD) and to identify
      predictors that influence HRQoL outcome after LARS. METHODS: Between 2011 and
      2013, 25 patients with therapy-resistant GERD [median age 6 (2-18) years] were
      included prospectively. Caregivers and children with normal neurodevelopment (>4
      years) were asked to fill out the validated PedsQL 4.0 Generic Core Scales before
      and 3-4 months after LARS. RESULTS: The PedsQL was completed by all caregivers (n
      = 25) and 12 children. HRQoL total score improved significantly after LARS, both
      from a parental (p = 0.009) and child's perspective (p = 0.018). The psychosocial
      health summary and physical health summary scores also improved significantly
      after LARS. HRQoL before and after LARS was significantly lower in children with
      impaired neurodevelopment (p < 0.001). However, neurodevelopment did not
      influence the effect of LARS on HRQoL. The only significant predictor for
      improvement in HRQoL after LARS was age at the time of operation (p = 0.001).
      CONCLUSIONS: HRQoL significantly improves after LARS. Although children with
      impaired neurodevelopment had lower overall HRQoL, neurodevelopment by itself
      does not predict inferior improvement in HRQoL after LARS. Older children have a
      more favorable HRQoL outcome after LARS compared to younger children. This may
      suggest caution when considering LARS in younger GERD patients.

PMID- 27864716
TI  - Single-incision laparoscopic surgery increases the risk of unintentional thermal
      injury from the monopolar "Bovie" instrument in comparison with traditional
      laparoscopy.
AB  - BACKGROUND: Single-incision laparoscopic surgery (SILS) places multiple
      instruments in close, parallel proximity, an orientation that may have
      implications in the production of stray current from the monopolar "Bovie"
      instrument. The purpose of this study was to compare the energy transferred
      during SILS compared to traditional four-port laparoscopic surgery (TRD). METHOD:
      In a laparoscopic simulator, instruments were inserted via SILS or TRD setup. The
      monopolar generator delivered energy to a laparoscopic L-hook instrument for 5-s
      activations on 30-Watts coag mode. The primary outcome (stray current) was
      quantified by measuring the heat of liver tissue held adjacent to the non
      electrically active 10-mm telescope tip and Maryland grasper in both the SILS and
      TRD setups. To control for the potential confounder of stray energy coupling via
      wires outside the surgical field, the camera cord and active electrode wires were
      oriented parallel or completely separated. RESULTS: SILS and TRD setups create
      similar amounts of stray current as measured by increased tissue temperature at
      the non-electrically active telescope tip (41 +/- 12 vs. 39 +/- 10  degrees C; p
      = 0.71). Stray current was greater in SILS compared to TRD at the tip of the non
      electrically active Maryland forceps (38 +/- 9 vs. 20 +/- 10  degrees C; p <
      0.01). Separation of the active electrode and camera cords did not change the
      amount of stray energy in the SILS orientation for either telescope (39 +/- 10 
      degrees C bundled vs. 36 +/- 10  degrees C separated; p = 0.40) or grasper (38 +/
      9  degrees C bundled vs. 34 +/- 11  degrees C separated; p = 0.19) but did in
      the TRD orientation (41 +/- 12 bundled vs. 24 +/- 10 separated; p < 0.01). When
      SILS was compared to TRD with the cords separated, SILS increased stray energy at
      both the telescope tip and grasper tip (36 +/- 10 vs. 24 +/- 10  degrees C; p <
      0.01 and 34 +/- 11 vs. 17 +/- 8  degrees C; p < 0.01). CONCLUSION: SILS increases
      stray energy transfer nearly twice as much as TRD with the use of the monopolar
      instrument. Strategies to mitigate the amount of stray energy in the TRD setup
      such as separation of the active electrode and camera cords are not effective in
      the SILS setup. These practical findings should enhance surgeons using the SILS
      approach of increased stray energy that could result in injury.

PMID- 27864717
TI  - Intraoperative localization of the parathyroid glands with indocyanine green and
      Firefly(R) technology during BABA robotic thyroidectomy.
AB  - BACKGROUND: It is unclear whether near-infrared (NIR) light-induced indocyanine
      green (ICG) fluorescence can effectively identify, and thus permit the
      preservation of, parathyroid glands in bilateral axillo-breast approach (BABA)
      robotic thyroidectomy. This case-control study with a prospectively recruited
      consecutive series and a retrospectively selected control group assessed the
      usefulness of ICG with Firefly(R) technology to identify the parathyroid glands
      intraoperatively during BABA robotic thyroidectomy. METHODS: All consecutive
      patients (N = 22) who were scheduled to undergo BABA robotic thyroidectomy for
      papillary thyroid carcinoma in December 2013-August 2015 and met the study
      eligibility criteria were recruited prospectively. ICG fluorescence was used with
      the Firefly system (NIR illuminator: 805 nm; filter: 825 nm) integrated in the da
      Vinci Si robot system to identify the lower parathyroid glands. Parathyroid
      hormone levels were recorded on postoperative days 0, 1, 2, and 14. Propensity
      score matching was used to identify an age-, gender-, tumor size-, and operation
      type-matched group of control patients who underwent BABA robotic thyroidectomy
      without the Firefly system. The two groups were compared in terms of parathyroid
      related outcomes. RESULTS: ICG fluorescence-mediated identification of the
      parathyroid and thyroid glands required on average (range) 203 +/- 89 (125-331)
      and 207 +/- 112 (130-356) s, respectively. The mean (range) fluorescence duration
      in these glands was 20.8 +/- 6.0 (16.6-35.8) and 20.1 +/- 7.3 (15.5-33.8) min,
      respectively. The ICG group had a significantly lower rate of incidental
      parathyroidectomy than the control group (0 vs. 15.9%, P = 0.048). CONCLUSIONS:
      ICG with NIR light may feasibly and safely identify the parathyroid glands in
      BABA robotic thyroidectomy.

PMID- 27864718
TI  - Phosphate tablets or polyethylene glycol for preparation to colonoscopy? A
      multicentre non-inferiority randomized controlled trial.
AB  - BACKGROUND: Adequate bowel preparation is a crucial step in colonoscopy procedure
      and has been identified as the cornerstone of a quality colonoscopy. Polyethylene
      glycol (PEG) for bowel cleansing still had up to 10 % unprepared colon. AIM: We
      herein compare efficacy, acceptability, tolerance and safety of sodium phosphate
      (NaP) tablets and split-dose PEG for bowel cleansing. PATIENTS AND METHODS: A
      prospective non-inferiority randomized trial was performed and registered on
      www.clinicaltrials.gov (NCT01840553). Patients were randomized to either 32 NaP
      tablets or 4 L of PEG. Blind readers assessed the efficacy of colon cleansing
      using the Boston Bowel Preparation Scale (BBPS). RESULTS: A total of 461 patients
      were randomized in groups (NaP group: n = 231; PEG group: n = 230). Median age
      was 54 and 52 in NaP group and PEG group, respectively (p < 0.01). Patients
      experienced an overall compliance to the treatment in 99.6 and 94.1 % in the NaP
      group and in the PEG group, respectively (p < 0.001). The mean time of withdrawal
      was 15.1 +/- 8.9 and 15.4 +/- 9.5 min in the NaP group and in the PEG group,
      respectively (p = 0.95). The good quality of bowel preparation, defined as BBPS
      score >=7, was obtained in 86.4 and 89.0 % of cases in the NaP group and in the
      PEG group, respectively (p = 0.42). In all segment (right colon, transverse colon
      and left colon and rectum), the NaP group was non-inferior to the PEG group.
      Bowel prep regimen was more frequently considered as "easy" by patients from the
      NaP group (54.8 % of patients) than patients from the PEG group (29.0 % of
      patients; p < 0.001). No serious adverse events were reported. No statistical
      differences were found between the NaP group and the PEG group concerning the
      incidence of an adverse event (338 vs. 322, respectively). CONCLUSION: While NaP
      tablets appeared as efficient as PEG in terms of colon cleansing prior to a
      colonoscopy, they significantly improved the overall compliance and eased product
      administration. At an era where bowel cleansing appears to be the cornerstone of
      a quality colonoscopy, NaP tablets in patients without contraindication might be
      considered as an option.

PMID- 27864719
TI  - Routine staging with endoscopic ultrasound in patients with obstructing
      esophageal cancer and dysphagia rarely impacts treatment decisions.
AB  - BACKGROUND: Endoscopic ultrasound (EUS) has been routinely utilized for the
      locoregional staging of esophageal cancer. One important aspect of clinical
      staging has been to stratify patients to treatment with neoadjuvant
      chemoradiation or primary surgical therapy. We hypothesized that EUS may have a
      limited impact on clinical decision making in patients with dysphagia and
      obstructing esophageal masses. METHODS: This retrospective cohort study included
      all patients with esophageal adenocarcinoma undergoing esophageal EUS between
      July 2008 and September 2013. Dysplastic Barrett's esophagus without invasive
      adenocarcinoma or incomplete staging was excluded. Patient demographics,
      endoscopic tumor characteristics, the presence of dysphagia, sonographic staging,
      and post-EUS therapy were recorded. Pathologic staging for patients who underwent
      primary surgical therapy was also recorded. Locally advanced disease was defined
      as at least T3 or N1, as these patients are typically treated with neoadjuvant
      therapy. RESULTS: Two hundred sixteen patients underwent EUS for esophageal
      adenocarcinoma, with 147 (68.1%) patients having symptoms of dysphagia on initial
      presentation. Patients with dysphagia were significantly more likely to have
      locally advanced disease on EUS than patients without dysphagia (p < 0.0001).
      Additionally, 145 (67.1%) patients had a partially or completely obstructing mass
      on initial endoscopy, of which 136 (93.8%) were locally advanced (p < 0.0001 vs.
      non-obstructing lesions). CONCLUSIONS: An overwhelming majority of patients
      presenting with dysphagia and/or the presence of at least partially obstructing
      esophageal mass at the time of esophageal cancer diagnosis had an EUS that
      demonstrated at least locally advanced disease. The present study supports the
      hypothesis that EUS may be of limited benefit for management of esophageal cancer
      in patients with an obstructing mass and dysphagia.

PMID- 27864720
TI  - A comparative study of delta-shaped and conventional Billroth I anastomosis after
      laparoscopic distal gastrectomy for gastric cancer.
AB  - BACKGROUND: Delta-shaped anastomosis (DA) is a newly developed intracorporeal
      gastroduodenostomy. This meta-analysis is performed to compare the safety,
      feasibility and clinical outcomes of DA with conventional extracorporeal Billroth
      I anastomosis (B-I) after laparoscopic distal gastrectomy for gastric cancer.
      METHODS: Both randomized controlled trials (RCTs) and nonrandomized cohort
      studies comparing outcomes of DA and B-I after laparoscopic distal gastrectomy
      for gastric cancer were searched in electronic database. Surgical outcomes,
      postoperative recovery, postoperative complications and outcomes were pooled and
      compared by meta-analysis using RevMan 5.3 software. Weighted mean differences
      (WMDs), odds ratios and risk differences were calculated with 95% confidence
      intervals (CIs). P values of <0.05 were considered statistically significant.
      RESULTS: Eight nonrandomized cohort studies of 2450 patients were included. Meta
      analysis showed significantly less blood loss (WMD -28.72; 95% CI -49.21 to 
      8.23; P = 0.006), more lymph nodes retrieved (WMD 3.23; 95% CI 0.86-5.61; P =
      0.008), shorter time to first soft diet (WMD -0.34; 95% CI -0.47 to -0.21, P <
      0.00001), less pain and analgesic use (WMC -0.29; 95% CI -0.56 to -0.02; P =
      0.03) in DA than in B-I. Both methods had similar operative time, resection
      margin, time to first flatus, length of hospital stay and rate of complications.
      Most of the postoperative symptoms were comparable between groups. The subgroup
      of obese patient showed more favorable outcomes in DA, and the learning curve of
      DA is steep. CONCLUSION: DA is a safe and feasible reconstruction method after
      laparoscopic distal gastrectomy, with comparable postoperative surgical outcomes,
      postoperative complications comparing to B-I. DA is less invasive with quicker
      resume of diet than B-I, especially for the obese patients.

PMID- 27864722
TI  - Comparison between submucosal tunneling endoscopic resection and endoscopic full
      thickness resection for gastric stromal tumors originating from the muscularis
      propria layer.
AB  - BACKGROUND: Both submucosal tunneling endoscopic resection (STER) and endoscopic
      full-thickness resection (EFTR) are effective method for treating gastric
      gastrointestinal stromal tumors (GISTs); however, little is known about the
      comparison between STER and EFTR. The aim of the study was to compare the safety
      and efficacy of STER and EFTR for treating gastric GIST. METHODS: We
      retrospectively collected the clinical data about patients with gastric GISTs who
      received STER or EFTR at our hospital from April 2011 to June 2016.
      Epidemiological data (gender, age), tumor size, procedure-related parameters,
      complications, length of stay, cost and follow-up data were compared between STER
      and EFTR. RESULTS: A total of 52 patients were enrolled, and 20 of them received
      STER, while the other 32 cases received EFTR. There was no significant difference
      between the two groups in terms of gender, age, concomitant diseases, tumor size,
      en bloc resection rate, operation time, complications, pathohistological grade of
      GIST, hospital stay and cost (P > 0.05). However, patients who received EFTR had
      a longer suture time and needed more clips to close the gastric-wall defect (STER
      vs EFTR, 291.5 +/- 68.7 vs 380.6 +/- 96.9s and 6.0 +/- 1.2 vs 7.6 +/- 1.6, P <
      0.05). No recurrence was noted in the STER and EFTR groups during a mean follow
      up of 10.9 and 23.8 months, respectively. CONCLUSIONS: The treatment efficacy
      between STER and EFTR for treating gastric GISTs was comparable, and a large
      scale, randomized study is necessary for a more confirmed conclusion.

PMID- 27864721
TI  - Intraoperative endoscopic nasobiliary drainage over primary closure of the common
      bile duct for choledocholithiasis combined with cholecystolithiasis: a cohort
      study of 211 cases.
AB  - BACKGROUND: Endoscopic nasobiliary drainage (ENBD) was often used for
      preoperative biliary drainage in cases like cholangiocarcinoma or acute
      obstructive suppurative cholangitis, reports on endoscopic nasobiliary drainage
      (ENBD) over primary closure of the common bile duct (CBD) are limited. This study
      compares outcomes of laparoscopic cholecystectomy (LC) + laparoscopic CBD
      exploration (LCBDE) + intraoperative ENBD + primary closure of CBD with
      equivalent patients who underwent preoperative endoscopic retrograde
      cholangiopancreatography (ERCP) and subsequent LC. METHODS: From January 2013 to
      December 2015, 829 consecutive patients with choledocholithiasis combined with
      cholecystolithiasis underwent surgery in our department. 211 patients underwent
      LC + LCBDE + intraoperative ENBD + primary closure of CBD (group A) and 117
      preoperative ERCP + subsequent LC (group B). A total of 501 patients (355 who
      underwent T-tube drainage and 146 who underwent transcystic exploration) were
      excluded from the analysis. Clinical records, operative findings, and
      postoperative follow-up were analyzed. RESULTS: Age and sex distribution,
      comorbidity, presentations, CBD diameter, and size and number of stones were
      similar in the two groups, and there was no postoperative mortality. Duration of
      surgery in group A was shorter (83 vs. 104 min, P < 0.01), as was postoperative
      hospital stay (6 vs. 9 days, P < 0.01). Average operative expenditure in group A
      was less than that of group B ($ 3816 vs. $ 4015, P < 0.01). The success rate in
      group A was higher (100 vs. 91%, P < 0.01). Ten patients in group B converted to
      LCBDE. The postoperative complication rate was higher in group B but without
      significant difference (1.9 vs. 4.2%, P = 0.29). Median follow-up time was 24 (3
      28) months (n = 302 patients). Two patients in group B reported residual stones.
      CONCLUSION: LC + LCBDE + intraoperative ENBD + primary closure of CBD should have
      priority over preoperative ERCP + subsequent LC for choledocholithiasis combined
      with cholecystolithiasis.

PMID- 27864723
TI  - Pre-treatment Eckardt score is a simple factor for predicting one-year peroral
      endoscopic myotomy failure in patients with achalasia.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel treatment for achalasia
      with excellent outcomes. But the predictor for treatment failure is not well
      defined. This study was aimed to prospectively investigate the factors for
      predicting failed POEM. METHODS: From June 2011 to May 2015, a total of 115
      achalasia patients treated by POEM were included for the retrospective cohort
      study from Nanfang Hospital and the First People's Hospital of Yunnan Province.
      Patients were followed up with Eckardt score, high-resolution manometry and
      endoscope. POEM failure was defined as primary failure (Eckardt score failed to
      decrease to 3 or below) and recurrences (decrease of Eckardt score to 3 or below,
      then rise to more than 3) during one-year follow-up. Univariate and multivariate
      Cox regression analyses were performed to assess the predictive factor. For the
      associated factor, receiver operating characteristic curve (ROC) was utilized to
      determine the cutoff value of the predicting factor. RESULTS: The failure rate of
      POEM after 1 year was 7.0% (8/115), including 5 primary failure cases and 3
      recurrences. Multivariate analysis showed higher pre-treatment Eckardt score was
      the single independent factor associated with POEM failure [9.5 (6-12) vs. 7 (2
      12), odds ratio (OR) 2.24, 95 confidence interval (95% CI) 1.39-3.93, p = 0.001].
      The cutoff value (Eckardt score >=9) had 87.5 sensitivity (95% CI 47.3-99.7%) and
      73.8% specificity (95% CI 64.4-81.9%) for predicting failed POEM. CONCLUSIONS:
      Pre-treatment Eckardt score could be a predictive factor for failed POEM. Eckardt
      score >=9 was associated with high sensitivity and specificity for predicting
      POEM failure.

PMID- 27864725
TI  - Endoscope-assisted extracapsular dissection of benign parotid tumors through a
      single cephaloauricular furrow incision versus a conventional approach.
AB  - BACKGROUND: A few modified approaches have been reported for performing endoscope
      assisted dissections of benign parotid tumors, but none that use incisions
      totally hidden in a natural furrow. This study evaluated the feasibility of
      performing endoscope-assisted extracapsular dissections of benign parotid tumors
      using a single cephaloauricular furrow incision. METHODS: Forty-six patients with
      benign parotid superficial lobe tumors were randomly divided into two groups: an
      endoscope-assisted (21 patients) group or a conventional (25 patients) surgery
      group. Perioperative and postoperative outcomes of the patients were evaluated,
      including the maximum diameter of the tumors, length of the incision, operating
      time, estimated blood loss during the operation, amount and duration of drainage,
      satisfaction scores based on the cosmetic results, perioperative complications,
      and follow-up information. RESULTS: The diameters of the tumors were comparable
      between the groups, and all operations were successfully performed as planned.
      The mean length of the incision in the endoscope-assisted group (3.6 +/- 0.5 cm)
      was significantly shorter than that in the conventional group (9.1 +/- 1.9).
      Meanwhile, the intraoperative blood loss, amount of drainage, perioperative
      complications, and cosmetic outcomes were all improved in the endoscope-assisted
      group. No tumor recurrence was found during 11-40 months of follow-up.
      CONCLUSIONS: Cephaloauricular furrow incisions were totally and naturally hidden
      in this procedure. Endoscope-assisted extracapsular dissections of benign parotid
      tumors via a small cephaloauricular furrow incision were found to be feasible and
      reliable, providing a minimally invasive approach and a satisfactory appearance.

PMID- 27864724
TI  - Cosmesis, patient satisfaction, and quality of life after da Vinci Single-Site
      cholecystectomy and multiport laparoscopic cholecystectomy: short-term results
      from a prospective, multicenter, randomized, controlled trial.
AB  - BACKGROUND: Single-incision laparoscopic cholecystectomy evolved from the
      traditional multiport laparoscopic technique. Prior trials have demonstrated
      improved cosmesis with the single-incision technique. Robotic single-site surgery
      minimizes the technical difficulties associated with laparoscopic single-incision
      approach. This is the first prospective, randomized, controlled study comparing
      robotic single-site cholecystectomy (RSSC) and multiport laparoscopic
      cholecystectomy (MPLC) in terms of cosmesis and patient satisfaction. METHODS:
      Patients with symptomatic benign gallbladder disease were randomized to RSSC or
      MPLC. Data included perioperative variables such as operative time, conversion
      and complications and cosmesis satisfaction, body image perception, quality of
      life using validated questionnaires, at postoperative visits of 2, 6 weeks and 3
      months. RESULTS: One hundred thirty-six patients were randomized to RSSC (N = 83)
      and MPLC (N = 53) at 8 institutions. Both cohorts were dominated by higher
      enrollment of females (RSSC = 78%, MPLC = 92%). The RSSC and MPLC cohorts were
      otherwise statistically matched. Operative time was longer for RSSC (61 min vs.
      44 min, P < 0.0001). There were no differences in complication rates. RSSC
      demonstrated a significant superiority in cosmesis satisfaction and body image
      perception (P value < 0.05 at every follow-up). There was no statistically
      significant difference in patient-reported quality of life. Multivariate analysis
      of female patients demonstrated significantly higher preference for RSSC over
      MPLC in cosmesis satisfaction and body image perception with no difference seen
      in overall quality of life. CONCLUSIONS: Results from this trial show that RSSC
      is associated with improved cosmesis satisfaction and body image perception
      without a difference in observed complication rate. The uncompromised safety and
      the improved cosmesis satisfaction and body image perception provided by RSSC for
      female patients support consideration of the robotic single-site approach.
      ClinicalTrials.gov identifier NCT01932216.

PMID- 27864726
TI  - Hand-assisted laparoscopic right hemicolectomy with complete mesocolic excision
      and central vascular ligation: a novel technique for right colon cancer.
AB  - BACKGROUND: It can be difficult to locate the superior mesenteric vein and
      dissect around middle colic vessels during laparoscopic right hemicolectomy with
      complete mesocolon excision due to a high rate of vascular variations in the
      superior mesenteric vessels. Therefore, we report a modified technique for hand
      assisted laparoscopic right hemicolectomy with complete mesocolic excision and
      central vascular ligation, which addresses these two problems. METHODS: Thirty
      one consecutive patients with right colon cancer underwent this procedure from
      March 2014 to August 2015. Extracorporeally, the transverse colon and distal
      ileum were excised with a transumbilical hand-port incision, and the distal part
      of the superior mesenteric vein was identified. Intracorporeally, with the
      assistance of the surgeon's left hand inserted through the incision, D3
      lymphadenectomy with central vascular ligation was performed, and the colon with
      the tumor, which had no blood supply, was removed. Patients' demographic data and
      intraoperative, postoperative and pathological characteristics were examined.
      RESULTS: The median operative time was 130.0 (range 115-180) minutes. The median
      blood loss was 45.0 (range 20-300) milliliters. The median length of the hand
      port incision was 7.3 (range 6.0-8.2) centimeters. The median numbers of lymph
      nodes and central lymph nodes was 34.0 (range 18-91) and 13.0 (range 3-28),
      respectively. Five (16.1%) of 31 patients had positive central lymph nodes.
      Specimen morphometric quantitation was as follows: the median distances from the
      tumor and nearest bowel wall to the high tie were 10.5 (range 5.0-15.0) and 8.0
      (range 6.0-12.0) centimeters, respectively; the median resected area of the
      mesentery was 200.0 (range 96.0-300.0) square centimeters; the median width of
      the chain of lymph-adipose tissue at the central lymph nodes area was 2.0 (range
      0.8-8.0) centimeters; and the median length of the central lymph-adipose chain
      was 19.0 (range 3.0-26.0) centimeters. CONCLUSIONS: Our procedure confers
      technical advantages and is feasible for treatment of right colon cancer.

PMID- 27864727
TI  - Post-translational modification by acetylation regulates the mitochondrial
      carnitine/acylcarnitine transport protein.
AB  - The carnitine/acylcarnitine transporter (CACT; SLC25A20) mediates an antiport
      reaction allowing entry of acyl moieties in the form of acylcarnitines into the
      mitochondrial matrix and exit of free carnitine. The transport function of CACT
      is crucial for the beta-oxidation pathway. In this work, it has been found that
      CACT is partially acetylated in rat liver mitochondria as demonstrated by anti
      acetyl-lys antibody immunostaining. Acetylation was reversed by the deacetylase
      Sirtuin 3 in the presence of NAD+. After treatment of the mitochondrial extract
      with the deacetylase, the CACT activity, assayed in proteoliposomes, increased.
      The half-saturation constant of the CACT was not influenced, while the V max was
      increased by deacetylation. Sirtuin 3 was not able to deacetylate the CACT when
      incubation was performed in intact mitoplasts, indicating that the acetylation
      sites are located in the mitochondrial matrix. Prediction on the localization of
      acetylated residues by bioinformatics correlates well with the experimental data.
      Recombinant CACT treated with acetyl-CoA was partially acetylated by non
      enzymatic mechanism with a corresponding decrease of transport activity. The
      experimental data indicate that acetylation of CACT inhibits its transport
      activity, and thus may contribute to the regulation of the mitochondrial beta
      oxidation pathway.

PMID- 27864728
TI  - Variation in pestivirus growth in testicle primary cell culture is more dependent
      on the individual cell donor than cattle breed.
AB  - The causes of bovine respiratory disease complex (BRDC) are multifactorial and
      include infection with both viral and bacterial pathogens. Host factors are also
      involved as different breeds of cattle appear to have different susceptibilities
      to BRDC. Infection with bovine pestiviruses, including bovine viral diarrhea
      virus 1 (BVDV1), BVDV2 and 'HoBi'-like viruses, is linked to the development of
      BRDC. The aim of the present study was to compare the growth of different bovine
      pestiviruses in primary testicle cell cultures obtained from taurine, indicine
      and mixed taurine and indicine cattle breeds. Primary cells strains, derived from
      testicular tissue, were generated from three animals from each breed. Bovine
      pestivirus strains used were from BVDV-1a, BVDV-1b, BVDV-2a and 'HoBi'-like
      virus. Growth was compared by determining virus titers after one passage in
      primary cells. All tests were run in triplicate. Virus titers were determined by
      endpoint dilution and RT-qPCR. Statistical analysis was performed using one way
      analysis of variance (ANOVA) followed by the Tukey's Multiple Comparison Test
      (P?0.05). Significant differences in virus growth did not correlate with cattle
      breed. However, significant differences were observed between cells derived from
      different individuals regardless of breed. Variation in the replication of virus
      in primary cell strains may reflect a genetic predisposition that favors virus
      replication.

PMID- 27864729
TI  - Assessment of right ventricular metabolism: An emerging tool for monitoring
      pulmonary artery hypertension.

PMID- 27864730
TI  - Design specifications for cellular regulation.
AB  - A critical feature of all cellular processes is the ability to control the rate
      of gene or protein expression and metabolic flux in changing environments through
      regulatory feedback. We review the many ways that regulation is represented
      through causal, logical, and dynamical components. Formalizing the nature of
      these components promotes effective comparison among distinct regulatory networks
      and provides a common framework for the potential design and control of
      regulatory systems in synthetic biology.

PMID- 27864731
TI  - Multiple Sclerosis-Related Pain Syndromes: An Imaging Update.
AB  - Pain in multiple sclerosis (MS) is a common manifestation, made up of complex
      phenomenon involving intricate neurophysiological processing at central levels of
      the pain pathway. Our understanding of the clinical and neurophysiological
      mechanisms of central/neuropathic pain related to MS continues to improve with
      improved imaging techniques but remains a challenging area of research. The
      advancements in imaging techniques for lesion evaluation of the various
      neuroanatomic structures have improved our detection, diagnosis, and
      understanding of MS pain and help validate subjective symptoms. This article will
      discuss the updated criteria of MS neuropathic pain and critically review some of
      the latest research into imaging correlations of MS pain syndromes. And discuss
      how advanced MRI imaging techniques (such as functional magnetic resonance
      imaging [fMRI], 3D imaging, fluid attenuated inversion recovery [FLAIR*], and
      diffusion tensor imaging [DTI]) have detailed neuropathic pain with a focus on
      migraines and trigeminal neuralgias and will highlight some of the ongoing
      limitations, variabilities, and deficiencies.

PMID- 27864732
TI  - Impact of pharmaceutical care on cardiovascular risk among older HIV patients on
      antiretroviral therapy.
AB  - Background Advances in the treatment of HIV infection have enabled better control
      of the disease, allowing patients to enjoy a longer life expectancy. However, the
      ageing of patients leads to an increased prevalence of cardiovascular disease.
      Various studies have found that pharmaceutical care results in better control of
      cardiovascular risk factors. Objective To measure the impact of pharmaceutical
      care on cardiovascular risk in patients older than 50 years receiving combination
      antiretroviral therapy. Setting Outpatient pharmacy service of a tertiary
      hospital, Spain. Methods A pre/post-intervention quasi-experimental clinical
      study was conducted in which health education and pharmacist interventions to
      reduce cardiovascular risk factors were carried out in a single patient cohort
      using the Dader method of pharmacotherapy, with a 12-month follow-up period per
      patient. Patients included were older than 50 years, with moderate/elevated
      cardiovascular risk. Data were obtained from patient clinical histories,
      dispensing records and patient interviews, and were subjected to statistical
      analysis. Main outcome measure Cardiovascular risk estimated by SCORE and REGICOR
      equations. Results Forty-two patients completed the study. Of these, 93 % were
      men, with an average age of 57 years and 15 years since diagnosis of HIV. A
      reduction was observed in the mean values (baseline vs. 12 months) of the
      following cardiovascular risk factors: systolic blood pressure (P = 0.009),
      diastolic blood pressure (P = 0.010), total cholesterol (P = 0.006), low-density
      lipoprotein cholesterol (LDL-c; P = 0.039), triglycerides (P = 0.010) and total
      cholesterol/high-density lipoprotein cholesterol (HDL-c; P < 0.001). An increase
      in HDL-c (P = 0.037) was also observed. The average cardiovascular risk estimated
      by the SCORE instrument was reduced from 7.6 % at the beginning of the study to
      6.4 % after 12 months (P = 0.039). The risk estimate according to REGICOR also
      decreased (P = 0.002). Over the 12-month period, 6.3 +/- 3.4 interventions were
      carried out per patient. Quantitative ineffectiveness was the most prevalent
      negative outcome associated with medication throughout the study, and
      noncompliance was the most frequent cause. Interventions on health education were
      the most common, followed by interventions on improving adherence. Conclusion
      Pharmaceutical care, delivered as a combination of health education and
      pharmacotherapy follow-up to outpatients at a tertiary hospital, had a positive
      impact on cardiovascular risk in patients older than 50 years receiving
      combination antiretroviral therapy.

PMID- 27864734
TI  - Myelin Genes and the Corpus Callosum: Proteolipid Protein 1 (PLP1) and Contactin
      1 (CNTN1) Gene Variation Modulates Interhemispheric Integration.
AB  - Interhemispheric communication during demanding cognitive tasks shows pronounced
      interindividual variation. Differences in interhemispheric transfer time are
      constituted by the relative composition of slow and fast fibers. The speed of
      axonal conduction depends on the diameter of the axon and its myelination. To
      understand the possible genetic impact of myelin genes on performance in the
      Banich-Belger Task, a widely used paradigm to assess interhemispheric
      integration, 453 healthy adults were genotyped for 18 single nucleotide
      polymorphisms (SNPs) in six myelin-related candidate genes. We replicated the
      typical pattern of results in the Banich-Belger Task, supporting the idea that
      performance on cognitively demanding tasks is enhanced when cognitive processing
      is distributed across the two hemispheres. Moreover, allelic variations in the
      proteolipid protein 1 gene PLP1 and the contactin 1 gene CNTN1 correlated with
      the extent to which individual performance is enhanced by interhemispheric
      integration. Variation in myelin genes possibly affects the microstructure of the
      corpus callosum by altering oligodendrocyte structure. Therefore, these results
      provide a foundation for understanding how genetics plays a role in modulating
      the efficacy of transcallosal transmission.

PMID- 27864733
TI  - (-)-Epicatechin, a Natural Flavonoid Compound, Protects Astrocytes Against
      Hemoglobin Toxicity via Nrf2 and AP-1 Signaling Pathways.
AB  - (-)-Epicatechin is a brain-permeable, natural product found at high
      concentrations in green tea and cocoa. Our previous research has shown that (-)
      epicatechin treatment reduces hemorrhagic stroke injury via nuclear factor
      erythroid 2-related factor 2 (Nrf2) signaling pathway in vivo. However, the
      mechanism of action of this compound in modulation of oxidant stress and in
      protection against hemoglobin-induced astrocyte injury is unclear. Therefore, we
      explored the cellular and molecular mechanisms that underlie these protective
      effects in vitro. Mouse primary astrocytes isolated from wild-type mice and Nrf2
      knockout (KO) mice were preconditioned with hemoglobin to simulate intracerebral
      hemorrhage (ICH) in vitro. Effects of (-)-epicatechin were measured by Western
      blotting, immunostaining, MTT assay, and reactive oxidant stress (ROS) assay. (-)
      Epicatechin increased Nrf2 nuclear accumulation and cytoplasmic levels of
      superoxide dismutase 1 (SOD1) in wild-type astrocytes but did not increase SOD1
      expression in Nrf2 knockout (KO) astrocytes. Furthermore, (-)-epicatechin
      treatment did not alter heme oxygenase 1 (HO1) expression in wild-type astrocytes
      after hemoglobin exposure, but it did decrease HO1 expression in similarly
      treated Nrf2 KO astrocytes. In both wild-type and Nrf2 KO astrocytes, (-)
      epicatechin suppressed phosphorylated JNK and nuclear expression of JNK, c-jun,
      and c-fos, indicating that inhibition of activator protein-1 (AP-1) activity by (
      )-epicatechin is Nrf2-independent. These novel findings indicate that (-)
      epicatechin protects astrocytes against hemoglobin toxicity through upregulation
      of Nrf2 and inhibition of AP-1 activity. These cellular and molecular effects may
      partially explain the cerebroprotection as we previously observed for (-)
      epicatechin in animal models of ICH.

PMID- 27864735
TI  - Environmental analysis of waste foundry sand via life cycle assessment.
AB  - The aim of this manuscript is to provide an environmental assessment of the
      creation and use of waste foundry sand (WFS) via an LCA in a foundry for grey
      cast iron. A life cycle impact assessment was carried out using SimaPro 8. This
      environmental analysis assessed the impact of creating waste foundry sand (WFS)
      in a foundry, Hronec (Slovakia, Central Europe). According to BREF, this foundry
      is classified as an iron foundry with a production capacity greater than 20 t/day
      with processes typical for grey cast iron foundries. Molten metal is poured into
      single-use sand moulds. We identified those factors influencing the creation and
      use of WFS which significantly affect the quality of the environment. The use of
      WFS from the production of cores in regenerated moulding mixtures with installed
      circuits brings marked minimisation of material and energy inputs in the
      processes of creating WFS and it positively influences the consumption of
      resources and the quality of the ecosystem. Space for lessening the impact of WFS
      processes upon the consumption of resources and ecosystem quality is mainly found
      in recycling WFS in the building sector. In the next step, it is necessary to
      thoroughly verify the eco-toxicological properties of not only the created WFS
      and other foundry waste, but mainly the building products for which this waste is
      used. In terms of transportation, it is important that waste is recycled at local
      level. The processes of creating WFS have a marked influence upon all the
      selected waste categories (consumption of resources, ecosystem quality, human
      health). By minimising material inputs into processes and the effective
      adjustment of production technology, a foundry can significantly lessen the
      impacts of processes for creating WFS upon the environment.

PMID- 27864736
TI  - Assessment of different route choice on commuters' exposure to air pollution in
      Taipei, Taiwan.
AB  - The purposes of this study are to develop a healthy commute map indicating
      cleanest route in Taipei metropolitan area for any given journey and to evaluate
      the pollutant doses exposed in different commuting modes. In Taiwan, there are
      more than 13.6 million motorcycles and 7.7 million vehicles among the 23 million
      people. Exposure to traffic-related air pollutants can thus cause adverse health
      effects. Moreover, increasing the level of physical activity during commuting and
      longer distances will result in inhalation of more polluted air. In this study,
      we utilized air pollution monitoring data (CO, SO2, NO2, PM10, and PM2.5) from
      Taiwan EPA's air quality monitoring stations in Taipei metropolitan area to
      estimate each pollutant exposure while commuting by different modes
      (motorcycling, bicycling, and walking). Spatial interpolation methods such as
      inverse distance weighting (IDW) were used to estimate each pollutant's
      distribution in Taipei metropolitan area. Three routes were selected to represent
      the variety of different daily commuting pathways. The cleanest route choice was
      based upon Dijkstra's algorithm to find the lowest cumulative pollutant exposure.
      The IDW interpolated values of CO, SO2, NO2, PM10, and PM2.5 ranged from 0.42-2.2
      (ppm), 2.6-4.8 (ppb), 17.8-42.9 (ppb), 32.4-65.6 (MUg/m3), and 14.2-38.9
      (MUg/m3), respectively. To compare with the IDW results, concentration of
      particulate matter (PM10, PM2.5, and PM1) along the motorcycle route was measured
      in real time. In conclusion, the results showed that the shortest commuting route
      for motorcyclists resulted in a much higher cumulative dose (PM2.5 3340.8 MUg/m3)
      than the cleanest route (PM2.5 912.5 MUg/m3). The mobile personal monitoring
      indicated that the motorcyclists inhaled significant high pollutants during
      commuting as a result of high-concentration exposure and short-duration peaks.
      The study could effectively present less polluted commuting routes for citizen
      health benefits.

PMID- 27864737
TI  - Significance of diazotrophic plant growth-promoting Herbaspirillum sp. GW103 on
      phytoextraction of Pband Zn by Zea mays L.
AB  - Microbe-assisted phytoremediation has been considered a promising measure for the
      remediation of heavy metal-polluted soil. The aim of this study was to assess the
      effect of diazotrophic plant growth-promoting Herbaspirillum sp. GW103 on growth
      and lead (Pb) and zinc (Zn) accumulation in Zea mays L. The strain GW103
      exhibited plant growth-promoting traits such as indole-3-acetic acid,
      siderophores, and 1-aminocyclopropane-1-carboxylic deaminase. Treatment of Z.
      mays L. plants with GW103 significantly increased 19, 31, and 52% of plant
      biomass and 10, 50, and 126% of chlorophyll a contents in Pb, Zn, and Pb + Zn
      amended soils, respectively. Similarly, the strain GW103 significantly increased
      Pb and Zn accumulation in shoots and roots of Z. mays L., which were 77 and 25%
      in Pb-amended soil, 42 and 73% in Zn-amended soil, and 27 and 84% in Pb + Zn
      amended soil. Furthermore, addition of GW103 increased 8, 12, and 7% of total
      protein content, catalase, and superoxide dismutase levels, respectively, in Z.
      mays L. plants. The results pointed out that isolate GW103 could potentially
      reduce the phytotoxicity of metals and increase Pb and Zn accumulation in Z. mays
      L. plant.

PMID- 27864738
TI  - Biochemical and histological biomarkers in the midgut of Apis mellifera from
      polluted environment at Beheira Governorate, Egypt.
AB  - The aim of this study was to analyze the impact of organophosphorus (OP)
      pollutants on oxidative stress and ultrastructural biomarkers in the midgut of
      the honeybee Apis mellifera collected from three locations that differ in their
      extent of spraying load with OP insecticides: a weakly anthropised rural site,
      Bolin which is considered as a reference site; moderately spraying site, El Kaza;
      and a strongly anthropised urban site, Tiba with a long history of pesticide use.
      Results showed that high concentrations of chlorpyrifos, malathion, diazinon,
      chlorpyrifos-methyl, and pirimiphos-methyl were detected in midgut at locations
      with extensive pesticide spraying. Reduced glutathione content, superoxide
      dismutase, catalase, and glutathione peroxidase displayed lowest activities in
      the heavily sprayed location (Tiba). Lipid peroxidation level in the midgut of
      honeybees in the sprayed locations was found to be significantly higher compared
      to the reference values. Meanwhile, various ultrastructural abnormalities were
      observed in the epithelial cells of midgut of honeybees collected from El Kaza
      and Tiba, included confluent and disorganized microvilli and destruction of their
      brush border, the cytoplasm with large vacuoles and alteration of cytoplasmic
      organelles including the presence of swollen mitochondria with lysis of matrices,
      disruption of limiting membranes, and disintegration of cristae. The nuclei with
      indented nuclear envelope and disorganized chromatin were observed. These
      investigated biomarkers indicated that the surveyed honeybees are being under
      stressful environmental conditions. So, we suggest using those biomarkers in the
      assessment of environmental quality using honeybees in future monitoring of
      ecotoxicological studies.

PMID- 27864739
TI  - Long-term 2007-2013 monitoring of reproductive disturbance in the dun sentinel
      Assiminea grayana with regard to polymeric materials pollution at the coast of
      Lower Saxony, North Sea, Germany.
AB  - During biological effect monitoring studies of endocrine active compounds with
      the snail Assiminea grayana in 2007-2013, reproductive disorders including
      atresia, transformation of capsule/albumen glands into prostates in females and
      ovotestis, transformation of prostates to capsule/albumen glands, disruption of
      spermatogenesis, and calcification of tubules in males, were encountered in
      several years. The search of sources of endocrine active substances was first
      directed to antifouling biocides from paint particles and extended to leaching
      compounds from polymeric materials. In contrast to the reference sites, most of
      the observed disorders occurred at a station near harbors and dockyards polluted
      with residues from antifouling paints and polymeric materials. Beside of
      investigations about the potential ingestion of polymer particles by the snails,
      further investigations of compounds of polymeric materials with endocrine
      potential should follow.

PMID- 27864740
TI  - Expression Levels of Warburg-Effect Related microRNAs Correlate with each Other
      and that of Histone Deacetylase Enzymes in Adult Hematological Malignancies with
      Emphasis on Acute Myeloid Leukemia.
AB  - Disruption of epigenetic regulation and characteristic metabolic alterations
      (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we
      investigated the expression levels of microRNAs and histone deacetylase enzymes
      via RT-qPCR in bone marrow specimens of adult patients suffering from
      hematological malignancies (total cohort n = 40), especially acute myeloid
      leukemia (n = 27). The levels of the three examined Warburg-effect related
      microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and
      the oncogenic miR-155 and miR-125b, while negatively with the level of the
      tumorsuppressor miR-124. Significant relationships have been confirmed between
      the levels of SIRT6, HDAC4 and the microRNAs listed above. In NPM1-mutated AML (n
      = 6), the level of miR-125b was significantly lower than in the group of AML
      patients not carrying this mutation (n = 13) (p < 0.05). In M5 FAB type of AML (n
      = 5), the level of miR-124 was significantly higher compared to the M2 group (n =
      7) (p < 0.05). In two cases of FAB M5 AML, the levels of SIRT6 and miR-26a
      increased during the first 4 weeks of treatment. In the total cohort, white blood
      cell count at the time of the diagnosis significantly correlated with the levels
      of HDAC4, SIRT6, miR-124 and miR-26a. Our results suggest that Warburg-effect
      related microRNAs may have important role in the pathogenesis of leukemia, and
      the potential oncogenic property of HDAC4 and SIRT6 cannot be excluded in
      hematological malignancies. Elevated level of miR-125b can contribute to adverse
      prognosis of AML without NPM1 mutation. The prevailment of the tumorsuppressor
      property of miR-124 may depend on the accompanying genetic alterations.

PMID- 27864741
TI  - An ultrasensitive label free nanobiosensor platform for the detection of cardiac
      biomarkers.
AB  - We report the fabrication of a label free nano biosensor platform comprising
      single nanofiber that is derived out of multi-walled carbon nanotubes (MWCNTs)
      embedded SU-8 photoresist, for the detection of three important human cardiac
      biomarkers viz., myoglobin (Myo), cardiac Troponin I (cTn I) and Creatine Kinase
      MB (CK-MB). These composite nanofibers were synthesized using electrospinning
      process. Single nanofibers were aligned between pairs of electrodes in-situ
      during the electrospinning process. The target proteins were detected using
      chemiresistive detection methodology. Each biomarker was detected using a
      specific, single, aligned nanofiber, functionalized with its corresponding
      monoclonal antibody. Chemiresistive detection involves measuring the change in
      conductance of the functionalized nanofibers upon the binding of the targeted
      antigen. The minimum detection limits of Myo, CK-MB and cTn I were experimentally
      found out to be as low as 6, 20 and 50 fg/ml respectively. No response was
      observed when the nanofibers were exposed to a non-specific protein,
      demonstrating excellent specificity to the targeted detection. These MWCNTs
      embedded SU-8 nanofibers based nanobiosensor platform shows great promise in the
      detection of cardiac markers and other proteins as they have fast response time,
      high sensitivity and good specificity.

PMID- 27864743
TI  - How to get a smoker addicted to quitting.

PMID- 27864742
TI  - A review of the application, feasibility, and the psychometric properties of the
      individualized measures in cancer.
AB  - PURPOSE: To identify from the published literature the feasibility and the
      application of the individualized measures [Patient Generated Index (PGI),
      Schedule for the Evaluation of Individual Quality of Life (SEIQOL), and the short
      form of it (the direct weighting SEIQOL-DW)] in the context of cancer and to
      summarize the evidence on the psychometric properties of these measures. METHODS:
      Ovid Medline, PubMed, Embase, and CINAHL were searched up to April 2016. All
      studies were included if they reported information about the psychometric
      properties of the individualized measures and included patients diagnosed with
      any type of cancer at any age. Effect size (ES) was calculated to test for the
      responsiveness. RESULTS: Fifty-four full articles were reviewed. Full-text
      assessment of these articles resulted in 27 eligible studies that were included
      in our analysis. The majority of the studies (81%) reported data on the SEIQOL
      DW, and only 15% on the PGI. Fourteen areas of quality-of-life (QOL) concerns
      were identified by patients using the PGI with the top 4 being family (90%),
      health (85%), finance (85%), and work (80%). At the global level, the correlation
      between the individualized and standard measures ranged from 0.45 to 0.49 and, at
      the symptom level, from 0.26 to 0.51. The ES of the individualized measures was
      high (ranged from 0.98 to 1.0) in the studies that expected high positive change
      compared to standard QOL measures (ES = 0.1). CONCLUSION: Individualized measures
      are feasible and acceptable among people with cancer and could easily be
      incorporated clinically and used in a research context. Individualized measures
      are sensitive to change and cover a wide range of patients QOL concerns in
      comparison with standard measures.

PMID- 27864746
TI  - Revalidation of the Sat-Chit-Ananda Scale.
AB  - Sat-Chit-Ananda is an indigenous construct that refers to absolute bliss and
      consciousness. The present study aimed to strengthen the psychometric properties
      of the newly developed Sat-Chit-Ananda scale (Singh et al. in Int J Vedic Found
      Manag 1(2):54-74, 2014). A total of 398 students aged 17-36 years (mean age =
      21.33 years, SD = 2.2, 70% males) participated in this study. An exploratory as
      well as confirmatory factor analysis was computed for the 17-item scale. Its'
      concurrent validity was established by assessing its correlation with other well
      being measures, namely Flourishing (Diener et al. in Soc Indic Res 97:143-156
      2010) and Scale of Positive and Negative Experience (Diener et al. 2010).
      Satisfactory results were obtained from both exploratory and confirmatory factor
      analyses. Sat-Chit-Ananda and its factors were found to be significantly
      positively correlated with Flourishing and Positive Experiences and were
      negatively correlated with Negative Experiences. Thus, the validity of the Sat
      Chit-Ananda (Singh et al. 2014) scale stands further substantiated-offering this
      scale as a promising new assessment tool.

PMID- 27864745
TI  - Use of Sedatives, Antidepressants and Antipsychotic Medicine among Seventh-day
      Adventists and Baptists in Denmark.
AB  - Earlier it has been found that female Seventh-day Adventists (SDA) and Baptists
      have an increased incidence of psychiatric affective disorders, in contrast to
      findings that religious practice is associated with better health. In this study,
      we examined whether the increase in incidence is due to less use of prescribed
      antidepressants, sedatives and antipsychotics by members of these religious
      societies than by the general population. In a cohort study, we examined records
      of all drugs redeemed by 3121 SDA and 2888 Baptists and 29,817 age- and gender
      matched members of the general population between 1995 and 2010 in the Danish
      Prescription Register and compared the prevalence and incidence of use of
      antidepressants, sedatives and antipsychotics. The prevalence of antidepressant
      use by women was lower in 1998 but no different from that in controls in 2003 and
      2008; the prevalence of antidepressant use by men was higher in both 1998 and
      2008 than in the Danish population. The incidence of antidepressant use was lower
      for female members in 1996-2000, but no difference was observed in the other
      periods. The prevalence and incidence of use of sedatives and antipsychotics did
      not consistently differ from those of the general population. The prevalence and
      incidence of use of antidepressants, sedatives and antipsychotics by female SDA
      and Baptists were not consistently lower than in the general Danish population.
      Our findings hence do not explain the increased incidence of psychiatric
      disorders among female members of these Danish religious societies.

PMID- 27864744
TI  - A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows
      Prediction of Human Brain Target Site Concentrations.
AB  - PURPOSE: Predicting target site drug concentration in the brain is of key
      importance for the successful development of drugs acting on the central nervous
      system. We propose a generic mathematical model to describe the pharmacokinetics
      in brain compartments, and apply this model to predict human brain disposition.
      METHODS: A mathematical model consisting of several physiological brain
      compartments in the rat was developed using rich concentration-time profiles from
      nine structurally diverse drugs in plasma, brain extracellular fluid, and two
      cerebrospinal fluid compartments. The effect of active drug transporters was also
      accounted for. Subsequently, the model was translated to predict human
      concentration-time profiles for acetaminophen and morphine, by scaling or
      replacing system- and drug-specific parameters in the model. RESULTS: A common
      model structure was identified that adequately described the rat pharmacokinetic
      profiles for each of the nine drugs across brain compartments, with good
      precision of structural model parameters (relative standard error <37.5%). The
      model predicted the human concentration-time profiles in different brain
      compartments well (symmetric mean absolute percentage error <90%). CONCLUSIONS: A
      multi-compartmental brain pharmacokinetic model was developed and its structure
      could adequately describe data across nine different drugs. The model could be
      successfully translated to predict human brain concentrations.

PMID- 27864747
TI  - Surgical Management of Metastatic Colorectal Cancer: A Single-Centre Experience
      on Oncological Outcomes of Pulmonary Resection vs Cytoreductive Surgery and
      HIPEC.
AB  - PURPOSE: Metastasectomy is accepted as standard of care for selected patients
      with colorectal pulmonary metastases (CLM); however, the role of cytoreductive
      surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for
      colorectal peritoneal metastases (CPM) is not universally accepted. We aim to
      compare oncological outcomes of patients with CLM and CPM after pulmonary
      resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and
      disease-free survival (DFS). METHODS: A retrospective review of 49 CLM patients
      who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in
      a single institution from January 2003 to March 2015, was performed. RESULTS: The
      5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p
      = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM
      patients had longer median operative time (8.38 vs. 1.75 h, p < 0.001), median
      hospital stay (13 vs. 5 days, p < 0.001), a higher rate of intensive care unit
      (ICU) admissions (67.3 vs. 8.2%, p < 0.001), and a higher rate of high-grade
      complications (17.3 vs. 4.1%, p < 0.001). Multivariate analysis demonstrated that
      recurrent lung metastasis after metastasectomy was an independent prognostic
      factor for OS of CLM patients (OR = 0.045, 95%, CL 0.003-0.622, p = 0.021). There
      were no independent prognostic factors for OS in CPM patients by multivariate
      analysis. There were no independent prognostic factors for DFS in CLM patients by
      multivariate analysis, but peritoneal cancer index score, bladder involvement,
      and higher nodal stage at presentation of the initial malignancy were independent
      prognostic factors for DFS in CPM patients. CONCLUSIONS: OS and DFS for CPM
      patients after CRS and HIPEC are comparable to CLM patients after lung resection,
      although morbidity appears higher. The prognostic factors affecting survival
      after surgery are different between CPM and CLM patients and must be considered
      when selecting patients for metastasectomy.

PMID- 27864749
TI  - Incidence and Impact of Unintentional Childhood Injuries: A Community Based Study
      in Rural South India.
AB  - OBJECTIVE: To estimate the incidence of unintentional childhood injuries and to
      assess the impact of injury during childhood. METHODS: This is a cross sectional
      study, conducted in 13 clusters of a rural block in Vellore. Children were
      screened by two-stage cluster sampling method by two weeks and three months
      recall method. The primary caregivers of injured children were administered a
      questionnaire to assess the impact of the injury. RESULTS: Childhood injury
      related morbidity was 292.5 per 1000 y. Children between 10 and 14 y (4.6%) and
      boys (4.5%) had a higher rate of injury. Fall (43.1 %) was the most common cause
      of injury followed by RTIs (Road Traffic Incidents- 27.6%). Work absenteeism for
      primary caregivers ranged from 1 to 60 (IQR 2-7) days. Sickness absenteeism
      ranged from 1 to 45 d with a mean of 7.64 (IQR 2-7) days. Half of the children
      missed school after an injury. The days spent with temporary disability ranged
      from 1 to 60 d with a mean of 11.79 (IQR 2-7) d and 7.73% had permanent
      disability. CONCLUSIONS: Unintentional childhood injury is a neglected public
      health problem which leads to sickness absenteeism and disability. Boys and older
      children are the most common victims of injury. There is a need for establishing
      state or nationwide injury registries to help understand accurate estimates of
      disability-adjusted life year (DALY) and loss of productivity.

PMID- 27864750
TI  - Survival and Short Term Outcomes of Very Preterm Infants.

PMID- 27864748
TI  - IRS1 and IRS2: molecular characterization, tissue expression and transcriptional
      regulation by insulin in yellow catfish Pelteobagrus fulvidraco.
AB  - The insulin receptor substrate (IRS) proteins, in particular, IRS1 and IRS2, are
      the key downstream players of insulin signaling pathway and the regulation of
      lipid metabolism. In the present study, two genes of IRS (IRS1 and IRS2) were
      isolated and characterized from yellow catfish Pelteobagrus fulvidraco. Their
      molecular characterizations, tissue expressions, and transcriptional levels by
      insulin both in vivo and in vitro were determined. The validated complementary
      DNAs encoding for IRS1 and IRS2 were 3693 and 3177 bp in length, encoding
      proteins of 1230 and 1058 amino acid residues, respectively. Similarly to
      mammals, amino acid sequence alignment revealed that IRSs contained an N-terminal
      pleckstrin homology (PH) domain, a phosphotyrosine-binding (PTB) domain, and
      several C-terminal multiple sites of tyrosine phosphorylation. Both IRS1 and IRS2
      were widely expressed across the ten tissues (liver, white muscle, spleen, brain,
      gill, mesenteric fat, anterior intestine, heart, mid-kidney, and ovary), but at
      the variable levels. Insulin injection at 1 MUg/g in vivo significantly
      stimulated the messenger RNA (mRNA) expression of IRS2, but not IRS1 mRNA
      expression levels in the liver of yellow catfish after 48 h. In hepatocytes of
      yellow catfish, insulin incubation significantly stimulated the IRS1 (at a 1000
      nM insulin group) and IRS2 (at both 100 and 1000 nM insulin groups) mRNA
      expressions, which indicated that IRS2 was more sensitive than IRS1 to insulin
      stimulation in the liver of yellow catfish, and IRS2 played a more important role
      in mediating insulin's effects on the liver metabolism. The present study serves
      to increase our understanding into the function of IRS in fish.

PMID- 27864752
TI  - Real-Time Analysis of the Apical Hook Development.
AB  - Mechanisms for cell protection are essential for survival of multicellular
      organisms. In plants, the apical hook, which is transiently formed in darkness
      when the germinating seedling penetrates towards the soil surface, plays such
      protective role and shields the vitally important shoot apical meristem and
      cotyledons from damage. The apical hook is formed by bending of the upper
      hypocotyl soon after germination, and it is maintained in a closed stage while
      the hypocotyl continues to penetrate through the soil and rapidly opens when
      exposed to light in proximity of the soil surface. To uncover the complex
      molecular network orchestrating this spatiotemporally tightly coordinated
      process, monitoring of the apical hook development in real time is indispensable.
      Here we describe an imaging platform that enables high-resolution kinetic
      analysis of this dynamic developmental process.

PMID- 27864751
TI  - Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory
      Syncytial Virus Infection Among Infants with Chronic Lung Disease.
AB  - INTRODUCTION: The REGAL (RSV evidence-a geographical archive of the literature)
      series provide a comprehensive review of the published evidence in the field of
      respiratory syncytial virus (RSV) in Western countries over the last 20 years.
      This third publication covers the risk and burden of RSV infection in infants
      with chronic lung disease (CLD), formerly called bronchopulmonary dysplasia
      (BPD). METHODS: A systematic review was undertaken of publications between
      January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane
      Library, and Clinicaltrials.gov. Studies reporting data for hospital
      visits/admissions for RSV infection among infants with CLD/BPD who were not
      prophylaxed, as well as studies reporting RSV-associated morbidity, mortality,
      and healthcare costs, were included. Burdens of disease data were compared with
      preterm infants without CLD/BPD, other high-risk groups and term infants. Study
      quality and strength of evidence (SOE) were graded using recognized criteria.
      RESULTS: A total of 1837 studies were identified and 39 were included. CLD/BPD is
      a significant independent risk factor for RSV hospitalization [RSVH (odds ratio
      2.2-7.2); high SOE]. Infants and young children with CLD/BPD had high RSVH rates
      which were generally similar in Europe, the United States, and Canada, mostly
      varying between 12 and 21%. Infants with CLD also had a longer length of hospital
      stay than other high-risk groups and term infants (high SOE). On average, infants
      spent 4-11 days in hospital (moderate SOE). Once hospitalized for RSV, affected
      children were at risk for a more severe course of disease than children with no
      RSVH (moderate SOE). CONCLUSION: Severe RSV infection in infants and young
      children with CLD/BPD poses a significant health burden in Western countries.
      Further studies focussing on the burden of RSV infection in this well-recognized
      population at high risk for severe disease are needed to help improve outcomes
      and plan allocation of healthcare resources. FUNDING: AbbVie.

PMID- 27864753
TI  - Grafting with Arabidopsis thaliana.
AB  - Generating chimeric organisms is an invaluable way to study cell-to-cell movement
      and non-cell-autonomous actions of molecules. Plant grafting is an ancient method
      of generating chimeric organisms and recently has been used to study the movement
      of hormones, proteins, and RNAs. Here, I describe a simple and efficient way to
      graft Arabidopsis thaliana at the seedling stage to generate plants with roots
      and shoots of different genotypes. Using this protocol, success rates of over 80
      % with up to 80 grafts assembled per hour can be achieved.

PMID- 27864754
TI  - Tips and Tricks for Exogenous Application of Synthetic Post-translationally
      Modified Peptides to Plants.
AB  - The first signaling peptide discovered and purified was insulin in 1921. However,
      it was not until 1991 that the first peptide signal, systemin, was discovered in
      plants. Since the discovery of systemin, peptides have emerged as a potent and
      diverse class of signaling molecules in plant systems. Peptides consist of small
      amino acid sequences, which often act as ligands of receptor kinases. However,
      not all peptides are created equal, and signaling peptides are grouped into
      several subgroups dependent on the type of post-translational processing they
      undergo. Here, we focus on the application of synthetic, post-translationally
      modified peptides (PTMPs) to plant systems, describing several methods
      appropriate for the use of peptides in Arabidopsis thaliana and crop models.

PMID- 27864755
TI  - Assaying Germination and Seedling Responses of Arabidopsis to Karrikins.
AB  - Karrikins are a small family of naturally occurring plant growth regulators
      present in the smoke and char produced from burning plant material in wildfires.
      They can stimulate germination of dormant seed and can influence seedling
      morphogenesis. Although Arabidopsis thaliana is not considered to be a smoke
      responsive species, karrikins will stimulate seed germination under the
      appropriate circumstances and will cause repression of hypocotyl elongation in
      low light. This chapter describes how to conduct assays of the activity of
      karrikins on Arabidopsis seeds and seedlings. The methods presented can
      potentially be modified for use in a range of Arabidopsis genotypes or in other
      plant species.

PMID- 27864756
TI  - Low-Cost Microprocessor-Controlled Rotating Stage for Medium-Throughput Time
      Lapse Plant Phenotyping.
AB  - Here we provide the instructions to build a cost-friendly rotating stage, which
      enables time-lapse phenotyping of seedlings, grown vertically on in vitro plates,
      in a medium-throughput manner.

PMID- 27864757
TI  - Genome-Wide Association Mapping of Root Traits in the Context of Plant Hormone
      Research.
AB  - Genome-wide association (GWA) mapping is a powerful method for the identification
      of alleles that underlie quantitative traits. It enables one to understand how
      genetic variation translates into phenotypic variation. In particular, plant
      hormone signaling pathways play a key role in shaping phenotypes. This chapter
      presents a protocol for genome-wide association mapping of root traits of
      Arabidopsis thaliana in the context of hormone research. We describe a specific
      protocol for acquiring primary and lateral root trait data that is appropriate
      for GWA studies using FIJI (ImageJ), and subsequent GWA mapping using a user
      friendly Internet application.

PMID- 27864758
TI  - High-Throughput Scoring of Seed Germination.
AB  - High-throughput analysis of seed germination for phenotyping large genetic
      populations or mutant collections is very labor intensive and would highly
      benefit from an automated setup. Although very often used, the total germination
      percentage after a nominated period of time is not very informative as it lacks
      information about start, rate, and uniformity of germination, which are highly
      indicative of such traits as dormancy, stress tolerance, and seed longevity. The
      calculation of cumulative germination curves requires information about
      germination percentage at various time points. We developed the GERMINATOR
      package: a simple, highly cost-efficient, and flexible procedure for high
      throughput automatic scoring and evaluation of germination that can be
      implemented without the use of complex robotics. The GERMINATOR package contains
      three modules: (I) design of experimental setup with various options to replicate
      and randomize samples; (II) automatic scoring of germination based on the color
      contrast between the protruding radicle and seed coat on a single image; and
      (III) curve fitting of cumulative germination data and the extraction, recap, and
      visualization of the various germination parameters. GERMINATOR is a freely
      available package that allows the monitoring and analysis of several thousands of
      germination tests, several times a day by a single person.

PMID- 27864759
TI  - Histochemical Staining of beta-Glucuronidase and Its Spatial Quantification.
AB  - Microscope images of plant specimens showing expression of GUS markers, besides
      being very beautiful, provide useful information regarding various biological
      processes. However, the information extracted from these images is often purely
      qualitative, and in many publications is not subjected to quantification. Here,
      we describe a very simple quantification method for GUS histochemical staining
      that enables detection of subtle differences in gene expression at cellular,
      tissue, or organ level. The quantification method described is based on the
      freely available image analysis software ImageJ that is widely used by the
      scientific community. We exemplify the method by quantifying small and precise
      changes (at the cellular level) as well as broad changes (at the organ level) in
      the expression of two previously published reporter lines, such as the
      pPILS2::GUS and pPILS5::GUS. The method presented here represents an easy tool
      for converting visual information from GUS histochemical staining images into
      quantifiable data and is of general importance for plant biologists performing
      GUS activity-based evaluation of reporter genes.

PMID- 27864760
TI  - Imaging TCSn::GFP, a Synthetic Cytokinin Reporter, in Arabidopsis thaliana.
AB  - Cytokinins are classical plant hormones that control numerous developmental
      processes throughout the plant life cycle. Cytokinin-responsive cells activate
      transcription via a phospho-relay signaling network. Type-B nuclear RESPONSE
      REGULATOR (RR) proteins mediate transcriptional activation as the final step in
      the signaling cascade. They bind to promoters of immediate-early target genes via
      a conserved Myb-related DNA-binding domain. To monitor transcriptional activation
      in response to a cytokinin stimulus, we have constructed a synthetic promoter,
      TCS (two-component signaling sensor) that harbors the concatemerized binding
      motifs for activated type-B RR in an optimized configuration. Here, we describe
      our protocols for imaging TCSn::GFP expression in transgenic Arabidopsis plants.
      The use of the fluorescent reporter GFP allows the visualization of cytokinin
      responding cells by fluorescent microscopy without the need for tissue processing
      steps, or staining reactions. This method is fast and with a low risk of
      artifacts. However, since cytokinin signaling integrates various environmental
      information including light, nutrient status, and biotic and abiotic stress,
      special care needs to be devoted to the control of growth conditions.

PMID- 27864761
TI  - Highlighting Gibberellins Accumulation Sites in Arabidopsis thaliana Root Using
      Fluorescently Labeled Gibberellins.
AB  - The physical location of plant hormones is an important factor in maintaining
      their proper metabolism, perception, and mediated developmental responses. Thus,
      unveiling plant hormones dynamics at the molecule's level is essential for a
      comprehensive, detailed understanding of both their functions and the regulative
      mechanisms they are subjected to. Here, we describe the use of fluorescently
      labeled, bioactive gibberellins (GAs) to highlight the dynamic distribution and
      accumulation sites of bioactive GAs in Arabidopsis thaliana roots by confocal
      microscopy.

PMID- 27864762
TI  - In Silico Methods for Cell Annotation, Quantification of Gene Expression, and
      Cell Geometry at Single-Cell Resolution Using 3DCellAtlas.
AB  - A comprehensive understanding of plant growth and development requires the
      integration of the spatial and temporal dynamics of gene regulatory networks with
      changes in cellular geometry during 3D organ growth. 3DCellAtlas is an
      integrative computational pipeline that semi-automatically identifies cell type
      and position within radially symmetric plant organs, and simultaneously
      quantifies 3D cell anisotropy and reporter abundance at single-cell resolution.
      It is a powerful tool that generates digital single-cell cellular atlases of
      plant organs and enables 3D cell geometry and reporter abundance
      (gene/protein/biosensor) from multiple samples to be integrated at single-cell
      resolution across whole organs. Here we describe how to use 3DCellAtlas to
      process and analyze radially symmetric organs, and to identify cell types and
      extract geometric cell data within these 3D cellular datasets. We detail how to
      use two statistical tools in 3DCellAtlas to compare cellular geometries, and to
      analyze reporter abundance at single-cell resolution.

PMID- 27864763
TI  - Analyzing Cell Wall Elasticity After Hormone Treatment: An Example Using Tobacco
      BY-2 Cells and Auxin.
AB  - Atomic force microscopy, and related nano-indentation techniques, is a valuable
      tool for analyzing the elastic properties of plant cell walls as they relate to
      changes in cell wall chemistry, changes in development, and response to hormones.
      Within this chapter I will describe a method for analyzing the effect of the
      phytohormone auxin on the cell wall elasticity of tobacco BY-2 cells. This
      general method may be easily altered for different experimental systems and
      hormones of interest.

PMID- 27864764
TI  - FRET-FLIM for Visualizing and Quantifying Protein Interactions in Live Plant
      Cells.
AB  - Proteins are the workhorses that control most biological processes in living
      cells. Although proteins can accomplish their functions independently, the vast
      majority of functions require proteins to interact with other proteins or
      biomacromolecules. Protein interactions can be investigated through biochemical
      assays such as co-immunoprecipitation (co-IP) or Western blot analysis, but such
      assays lack spatial information. Here we describe a well-developed imaging
      method, Forster resonance energy transfer (FRET) analyzed by fluorescence
      lifetime imaging microscopy (FLIM), that can be used to visualize protein
      interactions with both spatial and temporal resolution in live cells. We
      demonstrate its use in plant developmental research by visualizing in vivo
      dimerization of AUXIN RESPONSE FACTOR (ARF) proteins, mediating auxin responses.

PMID- 27864765
TI  - In Vivo Identification of Plant Protein Complexes Using IP-MS/MS.
AB  - Individual proteins often function as part of a protein complex. The
      identification of interacting proteins is therefore vital to understand the
      biological role and function of the studied protein. Here we describe a method
      for the in vivo identification of nuclear, cytoplasmic, and membrane-associated
      protein complexes from plant tissues using a strategy of immunoprecipitation
      followed by tandem mass spectrometry. By performing quantitative mass
      spectrometry measurements on biological triplicates, relative abundance of
      proteins in GFP-tagged complexes compared to background controls can be
      statistically evaluated to identify high-confidence interactors. We detail the
      entire workflow of this approach.

PMID- 27864766
TI  - Assaying Auxin Receptor Activity Using SPR Assays with F-Box Proteins and Aux/IAA
      Degrons.
AB  - The identification of TIR1 as an auxin receptor combined with advanced
      biophysical instrumentation has led to the development of real-time activity
      assays for auxins. Traditionally, molecules have been assessed for auxinic
      activity using bioassays, and agrochemical compound discovery continues to be
      based on "spray and pray" technologies. Here, we describe the methodology behind
      an SPR-based assay that uses TIR1 and related F-box proteins with surface plasmon
      resonance spectrometry for rapid compound screening. In addition, methods for
      collecting kinetic binding data and data processing are given so that they may
      support programs for rational design of novel auxin ligands.

PMID- 27864767
TI  - Studying Transcription Factor Binding to Specific Genomic Loci by Chromatin
      Immunoprecipitation (ChIP).
AB  - Plant hormone signaling involves complex transcriptional networks, where
      transcription factors orchestrate the control of specific gene expression. These
      networks include cross talk between hormone signaling pathways, and the
      integration of environmental signals and the developmental program. Understanding
      how particular transcription factors respond and integrate specific signals is
      crucial in order to understand the basic mechanisms of hormonal signaling and
      cross talk. Studying transcription factor binding at specific genomic loci by
      chromatin immunoprecipitation (ChIP) is therefore a valuable technique in order
      to analyze transcriptional regulation. The method is based on cross-linking
      proteins to DNA, the isolation of chromatin, and immunoprecipitation of a
      transcription factor of interest. The attached DNA is then recovered and analyzed
      by quantitative real-time PCR in order to establish binding sites of the
      respective transcription factor. Here, we present a relatively simple and short
      protocol for ChIP on single loci.

PMID- 27864768
TI  - Hormone Receptor Glycosylation.
AB  - Glycosylation is essential for all trees of life. N-glycosylation is one of the
      most common covalent protein modifications and influences a large variety of
      cellular processes including protein folding, quality control and protein
      receptor interactions. Despite recent progress in understanding of N-glycan
      biosynthesis, our knowledge of N-glycan function on individual plant proteins is
      still very limited. In this respect, plant hormone receptors are an interesting
      group of proteins as several of these proteins are present at distinct sites in
      the secretory pathway or at the plasma membrane and have numerous potential N
      glycosylation sites. Identifying and characterization of N-glycan structures on
      these proteins is essential to investigate the functional role of this abundant
      protein modification. Here, a straightforward immunoblot-based approach is
      presented that enables the analysis of N-glycosylation on endogenous hormone
      receptors like the brassinosteroid receptor BRI1.

PMID- 27864769
TI  - Highly Sensitive Salicylic Acid Quantification in Milligram Amounts of Plant
      Tissue.
AB  - Technical advances in mass spectrometry constantly raise the bar for analyzing
      trace amounts of plant hormones in only very small amounts of tissue. Here, a
      highly sensitive and accurate method is described for the quantitative analysis
      of the plant hormone salicylic acid not only in the model plant Arabidopsis
      thaliana but also in other plant species. The presented method is optimized for
      the working up of as little as 20 to 50 mg of plant tissue. The discussed
      protocol and the utilized laboratory equipment facilitate the implementation of
      the method into other laboratories that possess access to adequate state-of-the
      art gas chromatography-mass spectrometry (GC-MS) equipment.

PMID- 27864770
TI  - High-Resolution Cell-Type Specific Analysis of Cytokinins in Sorted Root Cell
      Populations of Arabidopsis thaliana.
AB  - We describe a method combining fluorescence-activated cell sorting (FACS) with
      one-step miniaturized isolation and accurate quantification of cytokinins (CKs)
      using ultra-high performance liquid chromatography-tandem mass spectrometry
      (UHPLC-MS/MS) to measure these phytohormones in specific cell types of
      Arabidopsis thaliana roots. The methodology provides information of unprecedented
      resolution about spatial distributions of CKs, and thus should facilitate
      attempts to elucidate regulatory networks involved in root developmental
      processes.

PMID- 27864771
TI  - Hormone Profiling in Plant Tissues.
AB  - Plant hormones are for a long time known to act as chemical messengers in the
      regulation of physiological processes during a plant's life cycle, from
      germination to senescence. Furthermore, plant hormones simultaneously coordinate
      physiological responses to biotic and abiotic stresses. To study the hormonal
      regulation of physiological processes, three main approaches have been used (1)
      exogenous application of hormones, (2) correlative studies through measurements
      of endogenous hormone levels, and (3) use of transgenic and/or mutant plants
      altered in hormone metabolism or signaling. A plant hormone profiling method is
      useful to unravel cross talk between hormones and help unravel the hormonal
      regulation of physiological processes in studies using any of the aforementioned
      approaches. However, hormone profiling is still particularly challenging due to
      their very low abundance in plant tissues. In this chapter, a sensitive, rapid,
      and accurate method to quantify all the five "classic" classes of plant hormones
      plus other plant growth regulators, such as jasmonates, salicylic acid,
      melatonin, and brassinosteroids is described. The method includes a fast and
      simple extraction procedure without time consuming steps as purification or
      derivatization, followed by optimized ultrahigh-performance liquid chromatography
      coupled to electrospray ionization-tandem mass spectrometry (UHPLC-MS/MS)
      analysis. This protocol facilitates the high-throughput analysis of hormone
      profiling and is applicable to different plant tissues.

PMID- 27864772
TI  - Use of Xenopus laevis Oocytes to Study Auxin Transport.
AB  - Xenopus laevis oocytes are an expression system that is particularly well suited
      for the characterization of membrane transporters. Oocytes possess only very
      little endogenous transport systems and therefore transporters can be studied
      with a high signal-to-noise ratio. This book chapter provides the basic methods
      to use Xenopus oocytes for the characterization of transporters by radiotracer
      experiments. While the methods described here were established to study auxin
      transport they can easily be adapted to study other hormone transporters and
      their substrates.

PMID- 27864773
TI  - Characterizing Auxin Response Circuits in Saccharomyces cerevisiae by Flow
      Cytometry.
AB  - Recapitulation of the nuclear auxin response pathway in Saccharomyces cerevisiae
      (yeast) provides a means to functionally assay the contribution of individual
      signaling components to response dynamics. Here, we describe a time course assay
      for characterizing auxin response circuits using flow cytometry. This method
      allows for quantitative measurements of the dynamic response of up to 12 circuits
      (strains) at once. We also describe a steady-state assay and how to utilize an R
      package we developed to facilitate data analysis.

PMID- 27864774
TI  - Comparison of an automatic analysis and a manual analysis of conjunctival
      microcirculation in a sheep model of haemorrhagic shock.
AB  - BACKGROUND: Life-threatening diseases of critically ill patients are known to
      derange microcirculation. Automatic analysis of microcirculation would provide a
      bedside diagnostic tool for microcirculatory disorders and allow immediate
      therapeutic decisions based upon microcirculation analysis. METHODS: After
      induction of general anaesthesia and instrumentation for haemodynamic monitoring,
      haemorrhagic shock was induced in ten female sheep by stepwise blood withdrawal
      of 3 * 10 mL per kilogram body weight. Before and after the induction of
      haemorrhagic shock, haemodynamic variables, samples for blood gas analysis, and
      videos of conjunctival microcirculation were obtained by incident dark field
      illumination microscopy. Microcirculatory videos were analysed (1) manually with
      AVA software version 3.2 by an experienced user and (2) automatically by AVA
      software version 4.2 for total vessel density (TVD), perfused vessel density
      (PVD) and proportion of perfused vessels (PPV). Correlation between the two
      analysis methods was examined by intraclass correlation coefficient and Bland
      Altman analysis. RESULTS: The induction of haemorrhagic shock decreased the mean
      arterial pressure (from 87 +/- 11 to 40 +/- 7 mmHg; p < 0.001); stroke volume
      index (from 38 +/- 14 to 20 +/- 5 ml.m-2; p = 0.001) and cardiac index (from 2.9
      +/- 0.9 to 1.8 +/- 0.5 L.min-1.m-2; p < 0.001) and increased the heart rate (from
      72 +/- 9 to 87 +/- 11 bpm; p < 0.001) and lactate concentration (from 0.9 +/- 0.3
      to 2.0 +/- 0.6 mmol.L-1; p = 0.001). Manual analysis showed no change in TVD
      (17.8 +/- 4.2 to 17.8 +/- 3.8 mm*mm-2; p = 0.993), whereas PVD (from 15.6 +/- 4.6
      to 11.5 +/- 6.5 mm*mm-2; p = 0.041) and PPV (from 85.9 +/- 11.8 to 62.7 +/-
      29.6%; p = 0.017) decreased significantly. Automatic analysis was not able to
      identify these changes. Correlation analysis showed a poor correlation between
      the analysis methods and a wide spread of values in Bland-Altman analysis.
      CONCLUSIONS: As characteristic changes in microcirculation during ovine
      haemorrhagic shock were not detected by automatic analysis and correlation
      between automatic and manual analyses (current gold standard) was poor, the use
      of the investigated software for automatic analysis of microcirculation cannot be
      recommended in its current version at least in the investigated model. Further
      improvements in automatic vessel detection are needed before its routine use.

PMID- 27864775
TI  - Assessing mercury contamination in a tropical coastal system using the mussel
      Perna perna and the sea anemone Bunodosoma caissarum.
AB  - Total mercury concentrations in the mussel Perna perna and the sea anemone
      Bunodosoma caissarum were determined to assess Hg contamination in Guanabara Bay,
      Rio de Janeiro, Brazil, and an adjacent sea area. Concentrations in the tissues
      of these species were compared. Average total mercury concentrations ranged from
      3.54 to 21.01 MUg kg-1 (wet wt.) in P. perna and from 4.51 to 23.19 MUg kg-1 (wet
      wt.) for B. caissarum. Concentrations varied according to the sampling stations.
      Distribution of concentrations for both species was similar along the sampling
      stations, and a significant correlation was observed. Results suggest that B.
      caissarum could be a suitable biomonitor species for mercury contamination in the
      study area and could be used as a complementary species for monitoring studies.
      Further research is, however, needed to assess how environmental conditions and
      other variables affect Hg concentrations in B. caissarum.

PMID- 27864776
TI  - Potable water quality monitoring of primary schools in Magura district,
      Bangladesh: children's health risk assessment.
AB  - Safe potable water is essential for good health. Worldwide, school-aged children
      especially in the developing countries are suffering from various water-borne
      diseases. In the study, drinking water supplies for primary school children were
      monitored at Magura district, Bangladesh, to ensure safe potable water. APHA
      standard analytical methods were applied for determining the physicochemical
      parameters of the water samples. For determination of the essential
      physicochemical parameters, the samples were collected from 20 randomly selected
      tube wells of primary schools at Magura. The metal contents, especially arsenic
      (As), iron (Fe), and manganese (Mn), in the water samples were analyzed by atomic
      absorption spectroscopy. The range of physicochemical parameters found in water
      samples were as follows: pH 7.05-9.03, electrical conductivity 400-2340 MUS/cm,
      chloride 10-640 mg/L, hardness 200-535 mg/L as CaCO3, and total dissolved solids
      208-1216 mg/L. The level of metals in the tube well water samples were as
      follows: As 1 to 55 MUg/L, Fe 40 to 9890 MUg/L, and Mn 10 to 370 MUg/L. Drinking
      water parameters of Magura district did not meet the requirement of the World
      Health Organization drinking water quality guideline, or the Drinking Water
      Quality Standards of Bangladesh.

PMID- 27864778
TI  - A Serious Games Platform for Cognitive Rehabilitation with Preliminary
      Evaluation.
AB  - In recent years Serious Games have evolved substantially, solving problems in
      diverse areas. In particular, in Cognitive Rehabilitation, Serious Games assume a
      relevant role. Traditional cognitive therapies are often considered repetitive
      and discouraging for patients and Serious Games can be used to create more
      dynamic rehabilitation processes, holding patients' attention throughout the
      process and motivating them during their road to recovery. This paper reviews
      Serious Games and user interfaces in rehabilitation area and details a Serious
      Games platform for Cognitive Rehabilitation that includes a set of features such
      as: natural and multimodal user interfaces and social features (competition,
      collaboration, and handicapping) which can contribute to augment the motivation
      of patients during the rehabilitation process. The web platform was tested with
      healthy subjects. Results of this preliminary evaluation show the motivation and
      the interest of the participants by playing the games.

PMID- 27864777
TI  - Bioaccumulation and cancer risk of polycyclic aromatic hydrocarbons in leafy
      vegetables grown in soils within automobile repair complex and environ in Uyo,
      Nigeria.
AB  - Using gas chromatography-mass spectrometry and an incremental lifetime cancer
      risks (ILCRs) assessment model, the bioaccumulation and cancer risk of 16 USEPA
      priority polycyclic aromatic hydrocarbons (PAHs) in leafy vegetables (Vernonia
      amygdalina and Lasianthera africanum) grown in soils within an automobile repair
      complex environment in Uyo, Nigeria was studied. The total PAHs concentrations
      recorded for soils ranged from 0.02 to 1.77 mg/kg. The highest level of 1.77
      mg/kg was recorded for soils from the main automobile repair complex (site 1).
      Low molecular weight (LMW) PAHs were predominant although some high molecular
      weight (HMW) PAHs suites (0.04 mg/kg of chrysene and 0.04 of
      benzo[k]fluoranthene) were also found in site 1. The leafy vegetables accumulated
      PAHs were mostly LMW. Accumulation levels were similar but the extent of PAH
      uptake in vegetables was species dependent as V. amygdalina accumulated more
      (0.81 mg/kg). The bioaccumulation factors (BaFs) calculated ranged from 0.22 to
      0.63 for L. africanum, and 0.18 to 0.55 for V. amygdalina in site 1 where high
      PAH levels were recorded in soil. Pearson correlation coefficient analysis
      revealed a strong positive relation between the PAH content of soil and the
      amount accumulated by L. africanum (r = 0.5) and V. amygdalina (r = 0.8) at p =
      0.05. The vegetable's potential to bioaccumulate PAHs is indicative of their use
      as good bioindicators for PAH contamination in soil. Only two of the USEPA
      possible human carcinogenic PAHs were detected, and carcinogenic risk assessment
      based on occupational exposures to soil particles by adults revealed that the
      total risk level (7.17 * 10-5) contribution from incidental soil ingestion,
      dermal contact, and soil particle dust inhalation slightly exceed the USEPA
      acceptable limits (< 1.00 * 10-5). There is a need for public education on
      consumption of vegetables grown in and around automobile repair complexes across
      Nigeria.

PMID- 27864779
TI  - Activity of novel inhibitors of Staphylococcus aureus biofilms.
AB  - Staphylococcus aureus is one of the most important pathogens causing chronic
      biofilm infections. These are becoming more difficult to treat owing to drug
      resistance, particularly because S. aureus biofilms limit the efficacy of
      antimicrobial agents, leading to high morbidity and mortality. In the present
      study, we screened for inhibitors of S. aureus biofilm formation using a natural
      product library from the Korea Chemical Bank (KCB). Screening by crystal violet
      based biomass staining assay identified hit compounds. Further examination of
      antibiofilm properties of these compounds was conducted and led to the
      identification of celastrol and telithromycin. In vitro, both celastrol and
      telithromycin were toxic to planktonic S. aureus and also active against a
      clinical methicillin-resistant S. aureus (MRSA) isolate. The effect of the
      compounds on preformed biofilms of clinical MRSA isolates was evaluated by
      confocal laser scanning microscopy (CLSM), which revealed the absence of typical
      biofilm architecture. In addition, celastrol and telithromycin inhibited the
      production of extracellular protein at selected sub-MIC concentrations, which
      revealed the reduced extracellular polymeric substance (EPS) secretion. Celastrol
      exhibited greater cytotoxicity than telithromycin. These data suggest that the
      hit compounds, especially telithromycin, could be considered novel inhibitors of
      S. aureus biofilm. Although the mechanisms of the effects on S. aureus biofilms
      are not fully understood, our data suggest that telithromycin could be a useful
      adjuvant therapeutic agent for S. aureus biofilm-related infections.

PMID- 27864781
TI  - Isolation, Identification and High-Throughput Screening of Neutral Lipid
      Producing Indigenous Microalgae from South African Aquatic Habitats.
AB  - Exploring indigenous microalgae capable of producing significant amounts of
      neutral lipids through high-throughput screening is crucial for sustainable
      biodiesel production. In this study, 31 indigenous microalgal strains were
      isolated from diverse aquatic habitats in KwaZulu-Natal, South Africa. Eight
      superior lipid-producing strains were selected for further analysis, based on
      Nile red fluorescence microscopy screening. The microalgal isolates were
      identified to belong to the genera Chlorella, Neochloris and Chlamydomonas via
      morpho-taxonomic and molecular approach by 18S rRNA gene sequencing. Chlorella
      vulgaris PH2 had the highest specific growth rate (MU) and lowest doubling time
      of 0.24 day-1 and 2.89 +/- 0.05 day-1, respectively. Chlorella vulgaris T4 had
      the highest biomass productivity of 35.71 +/- 0.03 mg L-1day-1. Chlorella
      vulgaris PH2 had the highest lipid content of 34.28 +/- 0.47 and 38 +/- 9.2%
      (dcw) as determined by gravimetric analysis and the sulfo-phospho-vanillin (SPV)
      method, respectively. Chlorella vulgaris PH2 exhibited a high content of
      saturated fatty acids, while Chlorella sp. T4 exhibited a high total content of
      saturated and monounsaturated fatty acids with a low content of polyunsaturated
      fatty acids. The preponderance of neutral lipids suggests that Chlorella sp. T4
      is a suitable candidate for biomass feedstock for biodiesel production.

PMID- 27864780
TI  - Inhibition of the nuclear export of p65 and IQCG in leukemogenesis by NUP98-IQCG.
AB  - NUP98 fuses with approximately 34 different partner genes via translocation in
      hematological malignancies. Transgenic or retrovirus-mediated bone marrow
      transplanted mouse models reveal the leukemogenesis of some NUP98-related fusion
      genes. We previously reported the fusion protein NUP98-IQ motif containing G
      (IQCG) in a myeloid/T lymphoid bi-phenoleukemia patient with t(3;11) and
      confirmed its leukemogenic ability. Herein, we demonstrated the association of
      NUP98-IQCG with CRM1, and found that NUP98-IQCG expression inhibits the CRM1
      mediated nuclear export of p65 and enhances the transcriptional activity of
      nuclear factor-kappaB. Moreover, IQCG could be entrapped in the nucleus by NUP98
      IQCG, and the fusion protein interacts with calmodulin via the IQ motif in a
      calcium-independent manner. Therefore, the inhibition of nuclear exports of p65
      and IQCG might contribute to the leukemogenesis of NUP98-IQCG.

PMID- 27864782
TI  - The cost of inpatient management of heart failure patients: a microcosting study
      in the Irish healthcare setting.
AB  - AIMS: To formally assess the resource use and cost of the inpatient treatment of
      heart failure (HF) from the health-payer's perspective. In addition, to compare
      costs in our cohort to (a) locally derived patient-level costs (PLC) and (b)
      national costs as per disease-related group (DRG). METHODS AND RESULTS: Study
      population Demographics and resource utilisation data were obtained from a cohort
      of 30 patients (57% male, mean age 70 years) admitted into a single tertiary
      centre with heart failure. Patients were identified retrospectively. Costing A
      microcosting approach was used to examine admission costs that were compared to
      PLC costs and DRG costs. Main outcome measure The bootstrap estimation was used
      to determine mean inpatient length of stay (LOS) with standard deviation (+/-SD)
      and mean costs +/-SD. RESULTS: The bootstrapped mean cost per HF episode was
      ?10,474 +/- 2478. The major cost drivers were ward stay (mean cost ?6068 +/-
      ?1681): laboratory costs (?1373 +/- 79) and cath lab costs (?1415 +/- 729). HF
      was more expensive to manage in patients <=65 years (?18,930 +/- 5546) compared
      to those aged over 65 years (?6209 +/- 1732); p = 0.001. No significant
      difference was found in managing heart failure in males (?11,035 +/- 3564) versus
      females (?9629 +/- 3294), p = 0.69. DRG costing frequently over or underestimated
      the admission cost. PLC costs were similar to microcosting derived costs. The
      bootstrapped mean LOS per HF episode was 15.7 days +/- 3.4. CONCLUSIONS: This
      study confirms that heart failure is a costly condition and that inpatient stay
      is the major cost driver. HF was significantly more expensive to manage in
      patients <=65 years compared to those aged over 65 years. DRG costing frequently
      over or underestimated the admission cost. Patient-level costs and microcosting
      are more accurate methods of costing inpatient HF admissions. To our knowledge,
      this is the first study of the cost of the inpatient treatment of HF within the
      context of the Irish healthcare setting.

PMID- 27864784
TI  - Capsule Commentary on Schiavoni et al., How Primary Care Physicians Integrate
      Price Information into Clinical Decision Making.

PMID- 27864785
TI  - Isolation Precautions for Hospitalized Patients: The Challenges of Identifying
      Unintended Individual Consequences and Measuring the Prevention of Community
      Harm.

PMID- 27864783
TI  - miR-26a-5p suppresses tumor metastasis by regulating EMT and is associated with
      prognosis in HCC.
AB  - OBJECTIVE: To determine the role of miR-26a-5p in tumor invasion and metastasis
      in hepatocellular carcinoma (HCC). METHODS: We evaluated miR-26a-5p expression in
      HCC tissues by quantitative PCR and then analyzed its clinical significance using
      a Cox regression model. Transwell and nude mouse models were used to examine
      tumor metastasis in vitro and in vivo, respectively. The relationship between miR
      26a-5p and epithelial-mesenchymal transition was also investigated by q-PCR and
      western blot. RESULTS: Strong downregulation of miR-26a-5p was observed in tumor
      tissues compared to paired adjacent normal tissues. Moreover, patients with low
      miR-26a-5p expression had a significantly poorer prognosis than those with high
      expression. The multivariate analysis indicated that miR-26a-5p expression was an
      independent prognostic indicator. The experimental transwell model and athymic
      mouse model revealed that miR-26a-5p depressed tumor metastasis in vitro and in
      vivo, respectively. In addition, the decreased miR-26a-5p level observed in HCC
      was associated with reduced E-cadherin expression and upregulation of vimentin,
      which affects the molecular mechanism of EMT. CONCLUSION: Downregulation of miR
      26a-5p promotes tumor metastasis by targeting EMT and influences the prognosis of
      HCC patients. Therefore, miR-26a-5p has potential as a new biomarker and
      therapeutic target.

PMID- 27864786
TI  - Clinical pharmacokinetics of an amorphous solid dispersion tablet of elacridar.
AB  - Elacridar is an inhibitor of the permeability glycoprotein (P-gp) and the breast
      cancer resistance protein (BCRP) and is a promising absorption enhancer of drugs
      that are substrates of these drug-efflux transporters. However, elacridar is
      practically insoluble in water, resulting in low bioavailability which currently
      limits its clinical application. We evaluated the in vitro dissolution and
      clinical pharmacokinetics of a novel amorphous solid dispersion (ASD) tablet
      containing elacridar. The dissolution from ASD tablets was compared to that from
      a crystalline powder mixture in a USP type II dissolution apparatus. The
      pharmacokinetics of the ASD tablet were evaluated in an exploratory clinical
      study at oral doses of 25, 250, or 1000 mg in 12 healthy volunteers. A target
      Cmax was set at >= 200 ng/mL based on previous clinical data. The in vitro
      dissolution from the ASD tablet was 16.9 +/- 3.7 times higher compared to that
      from a crystalline powder mixture. Cmax and AUC0-infinity increased linearly with
      dose over the explored range. The target Cmax of >= 200 ng/mL was achieved at the
      1000-mg dose level. At this dose, the Cmax and AUC0-infinity were 326 +/- 67
      ng/mL and 13.4 +/- 8.6 . 103 ng . h/mL, respectively. In summary, the ASD tablet
      was well tolerated, resulted in relevant pharmacokinetic exposure, and can be
      used for proof-of-concept clinical studies.

PMID- 27864787
TI  - Glycaemic Effects of Non-statin Lipid-Lowering Therapies.
AB  - Since the publication of the JUPITER trial, attention has been focused on the
      adverse glycemic effects of statin therapy. Although the modest increase in the
      risk of new diabetes mellitus is outweighed by the reduction in cardiovascular
      events for statins, emerging biochemical and genetic links between lipid
      metabolism and glycemic control raise the prospect of a broader diabetogenic
      effect of lipid-lowering therapies. For the novel and powerful PCSK9-inhibitor
      class available evidence does not support a major glycaemic effect with the
      results of large scale trials awaited although preliminary genetic data does
      suggest a link. In contrast, there is clear evidence of a diabetogenic effect for
      the now outdated but well-studied niacin. For ezetimibe and fibrates, evidence is
      scarce but currently broadly unconcerning. For now, the glycemic effects of lipid
      lowering therapies should have a limited influence on clinical decision-making.
      Further study in this topical area is needed.

PMID- 27864788
TI  - Reply to the Letter to the Editor: Editor's Spotlight/Take 5: No Benefit after
      THA Performed with Computer-assisted Cup Placement: 10-year Results of a
      Randomized Controlled Study.

PMID- 27864789
TI  - Informational Support in Pediatric Oncology: Review of the Challenges Among Arab
      Families.
AB  - Childhood cancer and its invasive treatment is a distressing life experience for
      the child and his family. Providing informational support is an essential part of
      community care, and defining parent's burden is an important part of this goal.
      However, providing such information can be particularly challenging in Arab
      countries where beliefs, traditions, religion, and socioeconomic factors
      influence parents' needs and their priorities of needs. This article presents a
      review of these specificities among Arab families. Implications of health-care
      providers are also discussed.

PMID- 27864791
TI  - The Harms of Antipsychotic Drugs: Evidence from Key Studies.
AB  - This safety assessment provides a detailed analysis of key studies and focuses on
      the six most widely used antipsychotic drugs. Lines of evidence include
      mechanisms of action, short-term treatment of psychosis, relapse prevention,
      early intervention in schizophrenia, long-term comparisons between first- and
      second-generation agents, and flexible treatment algorithms. Despite the
      diversity of study settings, several common features were seen. All the agents
      obstruct normal signaling through widely dispersed dopamine D2 receptors.
      Treatment failure or psychosis relapse was the most frequent outcome in most key
      studies, ranging from 38 to 93%. High discontinuation rates caused most trials to
      fail to demonstrate a substantial treatment benefit, or difference from an active
      comparator. Assessment of harm to the extrapyramidal motor system was confounded
      because of extensive neurological impairment from previous antipsychotic drug
      treatment measured at baseline, abrupt discontinuation effects, and high rates of
      concomitant medications to manage drug adverse effects. Claims that second
      generation antipsychotic drugs have safety advantages over classical neuroleptic
      drugs and prevent relapse were not supported in these key studies. The extent of
      injury to and impairment of multiple body systems caused by antipsychotic drugs
      shows the need for a scientific, clinical, and regulatory reappraisal of the
      appropriate use of these agents.

PMID- 27864790
TI  - Understanding pacing postconditioning-mediated cardiac protection: a role of
      oxidative stress and a synergistic effect of adenosine.
AB  - We and others have demonstrated a protective role for pacing postconditioning
      (PPC) against ischemia/reperfusion (I/R) injury in the heart; however, the
      underlying mechanisms behind these protective effects are not completely
      understood. In this study, we wanted to further characterize PPC-mediated cardiac
      protection, specifically identify optimal pacing sites; examine the role of
      oxidative stress; and test the existence of a potential synergistic effect
      between PPC and adenosine. Isolated rat hearts were subjected to coronary
      occlusion followed by reperfusion. PPC involved three, 30 s, episodes of
      alternating left ventricular (LV) and right atrial (RA) pacing. Multiple pacing
      protocols with different pacing electrode locations were used. To test the
      involvement of oxidative stress, target-specific agonists or antagonists were
      infused at the beginning of reperfusion. Hemodynamic data were digitally
      recorded, and cardiac enzymes, oxidant, and antioxidant status were chemically
      measured. Pacing at the LV or RV but not at the heart apex or base significantly
      (P < 0.001) protected against ischemia-reperfusion injury. PPC-mediated
      protection was completely abrogated in the presence of reactive oxygen species
      (ROS) scavenger, ebselen; peroxynitrite (ONOO-) scavenger, uric acid; and nitric
      oxide synthase inhibitor, L-NAME. Nitric oxide (NO) donor, snap, however
      significantly (P < 0.05) protected the heart against I/R injury in the absence of
      PPC. The protective effects of PPC were significantly improved by adenosine. PPC
      stimulated protection can be achieved by alternating LV and RA pacing applied at
      the beginning of reperfusion. NO, ROS, and the product of their interaction ONOO-
      play a significant role in PPC-induced cardiac protection. Finally, the
      protective effects of PPC can be synergized with adenosine.

PMID- 27864792
TI  - Readmission Risk in Chronic Obstructive Pulmonary Disease Patients: Comparative
      Study of Nebulized beta2-Agonists.
AB  - BACKGROUND: Bronchodilators are used for managing the symptoms of chronic
      obstructive pulmonary disease (COPD) and minimizing the risk of hospitalization
      and readmission. Hospital readmission is predictive of morbidity and mortality.
      OBJECTIVE: The study objective was to compare all-cause readmission risk in COPD
      patients receiving nebulized long-acting beta2-agonists (neb-LABAs) versus
      nebulized short-acting beta2-agonists (neb-SABA) following COPD-related
      hospitalization discharge. METHODS: This retrospective analysis utilized US-based
      pharmacy and medical claims records (2001-2011) to identify COPD patients aged
      >=40 years receiving neb-LABA or neb-SABA treatment within 30 days following
      discharge from a COPD-related hospitalization. Patients had to be continuously
      enrolled in their health plan for >=6 months before and after their first neb
      LABA or neb-SABA prescription fill (index date), and adherent to the treatment
      for the first 3 months post-index date. To select patients with similar severity
      profiles, neb-LABA and neb-SABA patients were matched by baseline
      characteristics. Readmission risks were observed over the 6-month period
      following the index date and compared between neb-LABA and neb-SABA cohorts using
      the multiple variable Cox proportional hazards model. RESULTS: The analysis
      included 246 matched patients (neb-LABA = 123; neb-SABA = 123). The mean age was
      67 years, and 54% were female. The average length of stay during index
      hospitalization was 4.4 days. After adjusting for potential confounders, the risk
      of readmission was 47% lower in the neb-LABA cohort than in the neb-SABA cohort
      (hazard ratio 0.53, 95% confidence interval 0.30-0.96; P = 0.0349). CONCLUSIONS:
      Patients receiving neb-LABAs had a significantly lower readmission risk within 6
      months following a COPD-related hospitalization versus patients treated with neb
      SABAs.

PMID- 27864793
TI  - Serum Fatty Acid-Binding Protein 4 is Increased in Patients with Psoriasis.
AB  - Psoriasis is associated with metabolic syndrome and cardiovascular disease. Fatty
      acid-binding proteins (FABP) have been recognized as predictors of these systemic
      disorders. The aim of this study was to assess correlations between levels of
      serum heart and adipocyte fatty acid-binding proteins (FABP3, FABP4) and disease
      severity, indicators of inflammation or metabolic disturbances, and topical
      treatment in psoriatic patients. Thirty-seven patients with relapse of plaque
      type psoriasis and 16 healthy volunteers were recruited. Blood samples were
      collected before and after 14 days of therapy. Serum FABP concentrations were
      examined by enzyme-linked immunosorbent assay for correlation with Psoriasis Area
      and Severity Index (PASI), body mass index (BMI), inflammatory or metabolic
      parameters, and treatment used. The median FABP4 serum levels were significantly
      increased (p = 0.038) in psoriatic patients, while FABP3 levels did not differ (p
      = 0.47) compared to the controls. No significant correlations were noted between
      the proteins and PASI, C-reactive protein (CRP), BMI, or levels of glucose or
      lipids. FABP3 significantly correlated with white blood count (p = 0.03) and
      aspartate aminotransferase (p = 0.04). After topical treatment, there was no
      significant change in serum FABP3 [11.5 (4.9-30.3) vs. 12.9 (3.5-30.3) ng/ml] (p
      = 0.96), whereas FABP4 was decreased [27,286 (20,344-32,257) vs. 23,034 (18,320
      29,874) pg/ml] (p = 0.12), losing its basal significance. FABP4 may be a marker
      of psoriasis, and FABP3 may be associated with inflammation or liver disorders in
      psoriatic patients. FABP do not appear to be useful for determining disease
      severity or the effectiveness of antipsoriatic treatment.

PMID- 27864794
TI  - Fatty Acids from a Glass Sponge Aulosaccus sp. Occurrence of New Cyclopropane
      Containing and Methyl-Branched Acids.
AB  - In order to identify new structures, the free fatty acids from an extract of a
      glass sponge Aulosaccus sp. (from the north-west Pacific) belonging to one of the
      least chemically investigated classes (Hexactinellida), were fractionated by RP
      HPLC and analyzed by NMR spectroscopy and GC-MS of their pyrrolidine derivatives,
      methyl(ethyl) esters and their dimethyl disulfide adducts. One hundred and twenty
      three C12-C31 acids (including nine new compounds) were detected, one hundred and
      ten of these compounds have not been found previously in glass sponges. The
      levels of common methylene-interrupted polyenes, monoenes of the (n-7) family and
      less common branched-chain components proved to be high. New acids were shown to
      be 5,13-dimethyl-tetradec-4-enoic, cis-10,11-methylene-heptadecanoic, 10,12
      dimethyl-octadecanoic, cis-12,13-methylene-nonadecanoic, (14E)-13-methyl-eicos-14
      enoic, 19-methyl-eicos-13-enoic, cis-20,21-methylene-heptacosanoic, 27-methyl
      octacos-21-enoic and (22Z)-nonacos-22-enoic. Some important mass spectrometric
      characteristics of pyrrolidides of homologous cyclopropane fatty acids are
      reported and discussed.

PMID- 27864796
TI  - Erratum to: Student-directed retrieval practice is a predictor of medical
      licensing examination performance.

PMID- 27864797
TI  - ?

PMID- 27864795
TI  - Prevalence of ocular surface disease symptoms and risk factors in group of
      university students in Monterrey, Mexico.
AB  - BACKGROUND: The objective of this study was to determine the prevalence of
      symptoms of ocular surface disease and its relationship with associated risk
      factors in students from the University of Monterrey using Ocular Surface Disease
      (OSDI) questionnaire. METHODS: A cross-sectional survey was conducted between
      October and December 2014 to assess the prevalence and risk factors for ocular
      surface disease in a group of students from Universidad de Monterrey in
      Monterrey, Mexico. The severity of the disease was measured via the Ocular
      Surface Disease Index (OSDI) questionnaire. RESULTS: The OSDI average value was
      26.85 +/- 20.79 points, with 70.4% of students (579) had OSDI score higher than
      12 points. Women had ocular surface disease 1.63 times more than men (OR 1.29,
      95% CI 1.13,1.48). Students who used ophthalmic drops have an OR 2.00 (95% CI
      1.65,2.40), and students who smoke have an OR 1.24 (95% CI 1.06,1.46). Use of
      contact lenses, hours in front of computer or history of refractive surgery has
      low-estimated effect on the probability of presenting an ocular disease.
      CONCLUSIONS: University students have a prevalence of 70.4% of ocular surface
      disease (OSD). OSD was associated with gender (women have a higher prevalence),
      smoking and the use of eye drops. A program to modify these risk factors to
      reduce the prevalence is needed.

PMID- 27864799
TI  - Primordial Prevention of Cardiometabolic Risk in Childhood.
AB  - Fetal life and childhood are important in the development of cardiometabolic risk
      and later clinical disease of atherosclerosis, hypertension and diabetes
      mellitus. Molecular and environmental conditions leading to cardiometabolic risk
      in early life bring us a challenge to develop effective prevention and
      intervention strategies to reduce cardiovascular (CV) risk in children and later
      disease. It is important that prevention strategies begin at an early age to
      reduce future CV morbidity and mortality. Pioneering work from longitudinal
      studies such as Bogalusa Heart Study (BHS), the Finnish Youth Study and other
      programs provide an awareness of the need for public and health services to begin
      primordial prevention. The impending CV risk beginning in childhood has a
      significant socioeconomic burden. Directions to achieve primordial prevention of
      cardiometabolic risk in children have been developed by prior longitudinal
      studies. Based on those studies that show risk factors in childhood as precursors
      of adult CV risk, implementation of primordial prevention will have effects at
      broad levels. Considering the epidemic of obesity, the high prevalence of
      hypertension and cardiometabolic risk, prevention early in life is valuable.
      Comprehensive health education, such as 'Health Ahead/Heart Smart', for all
      elementary school age children is one approach to begin primordial prevention and
      can be included in public education beginning in kindergarten along with the
      traditional education subject matter.

PMID- 27864798
TI  - Pharmacokinetic Drug Interactions with Panax ginseng.
AB  - Panax ginseng is widely used as an adaptogen throughout the world. The major
      active constituents of P. ginseng are ginsenosides. Most naturally occurring
      ginsenosides are deglycosylated by colonic bacteria to intestinal metabolites.
      Ginsenosides along with these metabolites are widely accepted as being
      responsible for the pharmacologic activity and drug interaction potential of
      ginseng. Numerous preclinical studies have assessed the influence of various
      ginseng components on cytochrome P450 (CYP), glucuronidation, and drug transport
      activity. Results from these investigations have been largely inconclusive due to
      the use of different ginseng products and variations in methodology between
      studies. Drug interaction studies in humans have been conflicting and have
      largely yielded negative results or results that suggest only a weak interaction.
      One study using a midazolam probe found weak CYP3A induction and another using a
      fexofenadine probe found weak P-gp inhibition. Despite several case reports
      indicating a drug interaction between warfarin and P. ginseng, pharmacokinetic
      studies involving these agents in combination have failed to find significant
      pharmacokinetic or pharmacodynamic interactions. To this end, drug interactions
      involving P. ginseng appear to be rare; however, close clinical monitoring is
      still suggested for patients taking warfarin or CYP3A or P-gp substrates with
      narrow therapeutic indices.

PMID- 27864800
TI  - Resistant Hypertension.
AB  - Conservatively, ten million people in the USA alone may suffer from RH and may be
      similarly prevalent elsewhere. Given the strong linear correlation between
      hypertension and cardiovascular outcomes, better control is paramount. We favor a
      multi-pronged approach. It may not suffice to address this by pharmacologic means
      only. Careful attention to modifiable risk factors, particularly sodium intake,
      adhering to a proper diet (i.e. DASH), and avoiding agents, i.e. non-steroidals,
      that can elevate the blood pressure, is key. Frequent follow up to establish the
      right treatment regimen and home blood pressuring monitoring can have a strong
      impact on control. Finally, consideration of device therapy may be a more viable
      option in the future.

PMID- 27864801
TI  - High Prevalence of Human Herpesvirus 8 Infection in Diabetes Type 2 Patients and
      Detection of a New Virus Subtype.
AB  - The prevalence of Human Herpesvirus 8 (HHV8) DNA and antiviral antibodies in
      Diabetes type 2 (DM2) and control subjects was studied, in order to confirm a
      possible link between DM2 and HHV8 infection. The HHV8-DNA from diabetic patients
      was typed for detecting possible genomic differences with known HHV8 reference
      viruses.DM2 patients and healthy controls were examined for the presence of HHV8
      DNA into the peripheral blood lymphocytes. Both anti-lytic and latent phase
      antibodies were detected in HHV8 positive and negative diabetic patients, as well
      in a number of controls. The HHV8 ORF K1 and ORF 26 genes from DM2 patients were
      typed and matched to reference strains.A significant prevalence of HHV8 DNA in
      DM2 subjects versus healthy controls was detected (about 58 % against 27 %). Anti
      lytic phase, but not anti-latent phase antibodies, were significantly increased
      in DM2 patients versus controls. In addition, about 30 % of HHV8 strains isolated
      from DM2 lymphocytes showed consistent differences in the ORF 26 gene sequence,
      so that a new HHV8 subtype was proposed. These findings give additional support
      to the hypothesis that HHV8 could be considered an additional risk factor for DM2
      onset.

PMID- 27864802
TI  - Secreted Phospholipase A2 Type IIA (sPLA2-IIA) Activates Integrins in an
      Allosteric Manner.
AB  - Secreted phospholipase A2 type IIA (sPLA2-IIA) is a well-established pro
      inflammatory protein and has been a major target for drug discovery. However, the
      mechanism of its signaling action has not been fully understood. We previously
      found that sPLA2-IIA binds to integrins alphavbeta3 and alpha4beta1 in human and
      that this interaction plays a role in sPLA2-IIA's signaling action. Our recent
      studies found that sPLA2-IIA activates integrins in an allosteric manner through
      direct binding to a newly identified binding site of integrins (site 2), which is
      distinct from the classical RGD-binding site (site 1). The sPLA2-IIA-induced
      integrin activation may be related to the signaling action of sPLA2-IIA. Since
      sPLA2-IIA is present in normal human tears in addition to rheumatoid synovial
      fluid at high concentrations the sPLA2-IIA-mediated integrin activation on
      leukocytes may be involved in immune responses in normal and pathological
      conditions.

PMID- 27864803
TI  - Enabling Rapid Response to the 2014-2016 Ebola Epidemic: The Experience and the
      Results of the National Institute for Infectious Diseases Lazzaro Spallanzani.
AB  - The unprecedented epidemic of Ebola virus disease (EVD) in West Africa
      highlighted the need for stronger systems for disease surveillance, response, and
      prevention worldwide. Tackling an epidemic event today requires a broader view,
      not only limited to medical management of the patients, but which also includes
      heroic efforts by clinicians and public health personnel.Since its foundation in
      1936, INMI has been devoted to the prevention, diagnosis and care for infectious
      diseases. In 2009, INMI became a WHO collaborative center for clinical care,
      diagnosis, response and training on Highly Infectious Diseases. This paper is
      aimed to present the activities and the challenging issues encountered by INMI
      during the 2014-2015 EVD outbreak in terms of preparedness and response to the
      epidemiological, clinical, diagnostic and research controversial aspects of EVD,
      both in Italy and in the field.

PMID- 27864805
TI  - Endocrine Hypertension: A Practical Approach.
AB  - Elevated blood pressure resulting from few endocrine disorders (endocrine
      hypertension) accounts for a high proportion of cases of secondary hypertension.
      Although some features may be suggestive, many cases of endocrine hypertension
      remain silent until worked up for the disease. A majority of cases result from
      primary aldosteronism. Other conditions that can cause endocrine hypertension
      are: congenital adrenal hyperplasia, Liddle syndrome, pheochromocytomas,
      Cushing's syndrome, acromegaly, thyroid diseases, primary hyperparathyroidism and
      iatrogenic hormone manipulation. Early identification and treatment of the cause
      of endocrine hypertension may help to reduce morbidity and mortality related to
      these disorders. This article gives a comprehensive and practical approach to the
      diagnosis and management of endocrine hypertension.

PMID- 27864804
TI  - Activity of Norspermidine on Bacterial Biofilms of Multidrug-Resistant Clinical
      Isolates Associated with Persistent Extremity Wound Infections.
AB  - Biofilm formation is a major virulence factor for numerous pathogenic bacteria
      and is cited as a central event in the pathogenesis of chronic human infections,
      which is in large part due to excessive extracellular matrix secretion and
      metabolic changes that occur within the biofilm rendering them highly tolerant to
      antimicrobial treatments. Polyamines, including norspermidine, play central roles
      in bacterial biofilm development, but have also recently been shown to inhibit
      biofilm formation in select strains of various pathogenic bacteria. The aim of
      this study was to evaluate in vitro the biofilm dispersive and inhibitory
      activities of norspermidine against multidrug-resistant clinical isolates of
      Acinetobacter baumannii(n = 4), Klebsiella pneumoniae (n = 3), Pseudomonas
      aeruginosa (n = 5) and Staphylococcus aureus (n = 4) associated with chronic
      extremity wound infections using the semi-quantitative 96-well plate method and
      confocal laser microscopy. In addition to the antibiofilm activity,
      biocompatibility of norspermidine was also evaluated by measuring toxicity in
      vitro to human cell lines and whole porcine tissue explants using MTT viability
      assay and histological analysis. Norspermidine (5-20 mM) had variable dispersive
      and inhibitory activity on biofilms which was dependent on both the strain and
      species. Of the clinical bacterial species evaluated herein, A. baumannii
      isolates were the most sensitive to the effect of norspermidine, which was in
      part due to the inhibitory effects of norspermidine on bacterial motility and
      expression of genes involved in the production of homoserine lactones and quorum
      sensing molecules both essential for biofilm formation. Importantly, exposure of
      cell lines and whole tissues to norspermidine for prolonged periods of time (>=24
      h) was observed to reduce viability and alter tissue histology in a time and
      concentration dependent manner, with 20 mM exposure having the greatest negative
      effects on both tissues and individual cell lines. Collectively our findings
      demonstrate that, similar to other polyamines, norspermidine displays both
      inhibitory and dispersive activities on biofilms of clinical multidrug-resistant
      bacterial isolates, in particular for strains of A. baumannii. Additionally our
      findings suggest that direct application may be considered on tissues, albeit for
      limited exposure times.

PMID- 27864806
TI  - Pathophysiological Mechanisms and Correlates of Therapeutic Pharmacological
      Interventions in Essential Arterial Hypertension.
AB  - Treating arterial hypertension (HT) remains a hard task. The hypertensive patient
      is often a subject with several comorbidities and metabolic abnormalities.
      Clinicians everyday have to choose the right drug for the single patient among
      the different classes of antihypertensives. Apart from lowering blood pressure, a
      main therapeutic target should be that of counteracting all the possible
      pathophysiological mechanisms involved in HT itself and in existing/potential
      comorbidities. All the ancillary positive and negative effects of the
      administered drugs should be considered: in particular, since hypertensive
      patients are often glucose intolerant/diabetic, carrier of serum lipids disorder,
      have already developed atherosclerotic diseases and endothelial dysfunction, they
      should not be treated with drugs negatively interfering with these conditions but
      with molecules that, if possible, improve them. The main pathophysiological
      mechanisms and correlates of therapeutic pharmacological interventions in
      essential HT are reviewed here.

PMID- 27864807
TI  - Assessing the Associations Between Awareness of Myocardial Infarction Symptoms,
      Socioeconomic Factors, and Cardiovascular Disease Risk Factors Through Regression
      Models.
AB  - There are few studies that consider the association between awareness of symptoms
      of acute myocardial infarction (MI), socioeconomic factors (household income,
      sex, race/ethnicity, and educational attainment), and cardiovascular (CVD) risk
      factors. It is important to understand these associations because there is
      evidence that suggests that disparities in the awareness of MI symptoms lead to
      disparities in delays in receiving treatment and outcomes of patients with MI.
      The study was to determine if there are disparities in the awareness of different
      MI symptoms among different groups with respect to self-reported race, ethnicity,
      education, age, and income (i.e., various SES factors) in the presence/absence of
      modifiable cardiovascular disease risk factors. We utilized the 2003-2009
      Behavioral Risk Factor Surveillance Survey, a nationally representative telephone
      based survey, to evaluate the relationships between five common symptoms of MI,
      socioeconomic factors, and four major modifiable CVD risk factors. We found that
      being college-educated, a higher household income, making $75,000 a year or more,
      being female, being non-Hispanic White, having hypertension, and exercising
      regularly were generally associated with a higher probability of being aware of
      the MI symptoms evaluated in this study. Additionally, awareness that
      jaw/back/neck pain and feeling weak/light-headed/faint are symptoms of MI were
      found to be consistently lower compared to that of other MI symptoms, ranging
      from 50 to 75%, across all SES factors and CVD risk factors. The findings from
      this study can serve as a useful guide to facilitating targeted educational
      efforts aimed at improving awareness of MI symptoms that may ultimately reduce
      disparities in the outcomes of patients at risk for MI.

PMID- 27864808
TI  - Latina and Black/African American Women's Perspectives on Cancer Screening and
      Cancer Screening Reminders.
AB  - INTRODUCTION: Racial and ethnic disparities continue to exist in cancer screening
      rates, especially among US Latina and Black/African American populations. We
      conducted six focus groups among 41 women from these communities in order to
      better understand their preferences about cancer screening reminders and the
      motivators and deterrents they face in obtaining recommended breast, cervical,
      and colon cancer screening. METHODS: Using self-reported patient race/ethnicity
      from electronic medical records of a large, integrated health care system in
      Seattle, we recruited women ages 30-60 to participate in one of five 2-hour focus
      groups. Using verbatim transcripts from these discussions, we conducted a
      qualitative analysis to identify common themes. RESULTS: The focus group
      participants were primarily strong endorsers and utilizers of recommended breast,
      cervical, and colon cancer screening services. Insurance and belief in preventive
      care were the most common motivators that they cited in obtaining cancer
      screening. However, they still reported multiple barriers to getting recommended
      cancer screening for themselves and community members, including lack of time,
      conflicting information about screening intervals, distrust in the health care
      system, and a lack of understanding of the benefits of preventive care.
      CONCLUSIONS: Efforts to improve understanding about the benefits of cancer
      screening, clarify cancer screening guideline recommendations, increase cultural
      competency among health care professionals, and expand the times and locations
      where cancer screening is available are all options that may improve cancer
      screening rates among Latinas and Black/African American women.

PMID- 27864809
TI  - Determinants of Prostate Cancer Screening Intentions of Young Black Men Aged 18
      to 40 Years.
AB  - INTRODUCTION: Black men are more likely to be diagnosed with prostate cancer,
      with higher stage and higher grade at presentation. Evidence suggests that for
      education in health promotion behaviors (such as screenings) in early adult
      years, young Black men can be better equipped to make informed decisions in later
      years. OBJECTIVE: Using the theory of reasoned action (TRA), we assessed the
      intention of young Black men to screen for prostate cancer when it is recommended
      and determined its correlates. METHODS: This was a cross-sectional study of 267
      Black men aged 18 to 40 years. A 47-item questionnaire collected information on
      demographics/personal factors, attitudes toward prostate cancer screening, social
      influence, comfortability with prostate examinations, cues to action, health
      screening experiences, knowledge of prostate cancer and screening, and intention.
      Descriptive statistics were calculated for all variables and hierarchical
      logistic regression was employed to determine significant predictors of prostate
      cancer screening intentions. RESULTS: The regression model accounted for 46% of
      the variance in intention (p < 0.01), with excellent perception of health, having
      private or public health insurance, longer regular source of care, positive
      attitude, positive social influence, positive cues to action, and higher
      knowledge levels being significant predictors of intentions. CONCLUSION: This
      study provides support for the use of TRA in predicting prostate cancer screening
      intentions among young Black men when it is recommended by a physician. Findings
      may inform the development of empirical-based interventions to educate and inform
      at-risk young Black men about the pros and cons of prostate cancer screening so
      that they can make informed decision on screening when recommended later in life.

PMID- 27864810
TI  - A case of Pitt-Hopkins syndrome presented with Angelman-like syndromic
      phenotypes.
AB  - Pitt-Hopkins syndrome (PTHS), caused by a TCF4 gene mutation, is a condition
      characterized by intellectual disability and developmental delay, breathing
      anomalies, epilepsy, and distinctive facial dysmorphism [1]. Its diverse clinical
      appearance causes pediatricians to confuse it with Angelman syndrome, which is
      considered one of the family members of Angelman-like syndrome. Herein, we report
      on a 4 y/o boy with PTHS and discuss its similarities and differences with
      Angelman syndrome. In doing so we hope to provide a feasible pathway to diagnose
      rare diseases, especially Angelman-like syndrome.

PMID- 27864813
TI  - Silex: A database for silent-letter endings in French words.
AB  - Silent-letter endings are often claimed to be a major source of inconsistency in
      the French orthography. In this report, we introduce Silex, a database designed
      to facilitate the study of spelling performance in general, and silent-letter
      endings in particular. It was derived from two large and recent corpora based on
      child- and adult-targeted material. Silex consists of three kinds of Excel
      workbooks: a set of Stimuli Selector workbooks that allow researchers to select
      words based on a variety of statistics and word characteristics; a Table
      Generator workbook that allows researchers to build consistency distribution
      tables by selecting specific phonological or orthographic units; and a Master
      File workbook, from which all statistics were derived, and that allows
      researchers to compute other statistics. Silex is different from existing
      databases in the manner that silent-letter endings were coded and how consistency
      indices were computed. Importantly, Silex provides unconditional- and conditional
      consistency indices for silent-letter endings. To demonstrate the utility of
      Silex, we first described the silent-letter phenomenon in French. We found that,
      at minimum, 28 % of French words end with a silent letter. Moreover, silent
      letter endings are usually t, e, s, x, or d, and the occurrence of these letters
      is conditioned by the phonological ending of words. Second, we showed how Silex
      could prove useful for the development of theoretical models and for empirical
      studies. The novel information provided in Silex as well as the flexibility of
      this database should enable researchers to advance our understanding of
      developing and skilled spelling performance.

PMID- 27864814
TI  - nodeGame: Real-time, synchronous, online experiments in the browser.
AB  - nodeGame is a free, open-source JavaScript/ HTML5 framework for conducting
      synchronous experiments online and in the lab directly in the browser window. It
      is specifically designed to support behavioral research along three dimensions:
      (i) larger group sizes, (ii) real-time (but also discrete time) experiments, and
      (iii) batches of simultaneous experiments. nodeGame has a modular source code,
      and defines an API (application programming interface) through which
      experimenters can create new strategic environments and configure the platform.
      With zero-install, nodeGame can run on a great variety of devices, from desktop
      computers to laptops, smartphones, and tablets. The current version of the
      software is 3.0, and extensive documentation is available on the wiki pages at
      http://nodegame.org .

PMID- 27864815
TI  - Delayed onset hypokinetic-rigid syndrome due to hypoxic-ischemic damage of the
      striatum.

PMID- 27864812
TI  - How In Vitro Assays Contribute to Allergy Diagnosis.
AB  - Diagnosis of allergic disorders is based upon the clinical history of the
      disease, the immunoglobulin E (IgE) antibody response, and the allergen exposure.
      During the last decade, many changes have occurred in the in vitro diagnostic
      tests used in daily practice. The most important one is the use of allergenic
      molecules, which helps to define severe profile of allergy and/or to better
      understand cross-reactivity. The correlation between IgE sensitization and
      bronchial or nasal response in provocation tests is not so clear, which implies
      that such tests are still helpful in allergy diagnosis. In order to strengthen
      the link between a real allergen exposure and allergic symptoms, environmental
      allergen load assessment can be performed. For clinicians, it appears obvious to
      know the pollen count to treat their patients; however, they rarely measure the
      allergen load in the indoor environment, while nowadays home-tests (semi
      quantitative or quantitative) make the assessment very easy. In the future,
      assessment of the environmental exposure (preferably with an indoor technician)
      of an allergic patient should take into account not only the allergens but also
      the other indoor pollutants, which could enhance respiratory symptoms in allergic
      patients.

PMID- 27864816
TI  - Giant insulinoma: report of a case and review of published reports.
AB  - BACKGROUND: Larger insulinomas are reportedly more likely to be malignant;
      however, their biological behavior has not been clearly elucidated. We here
      report the characteristics and treatment of a giant insulinoma with local
      invasion and lymph node metastasis. We also review published reports concerning
      the clinical features of giant insulinomas and comparing their grading with that
      of pancreatic neuroendocrine tumors. CASE PRESENTATION: A 71-year-old man was
      referred to our hospital for investigation of persistent hypoglycemia. On the
      current presentation, laboratory tests showed serum glucose, immunoreactive
      insulin, and C peptide concentrations of 45 mg/dL, 17.2 MUIU/mL and 4.1 ng/mL,
      respectively. Dynamic magnetic resonance imaging showed a hypervascular tumor
      measuring 13.5 cm in the head of the pancreas. Computed tomography scanning
      demonstrated local invasion and lymph node involvement. He thus had Whipple's
      triad, which is associated with malignant insulinoma. No distant metastases
      having been identified, pancreaticoduodenectomy was performed. Intraoperatively,
      three separate tumors were identified in the pancreatic head. Pathological
      examination showed all three tumors were pancreatic neuroendocrine tumors; the
      tumor cells in the largest mass were strongly immunoreactive for insulin. The Ki
      67 index was 2-5% in most parts of the largest tumor and over 20% in the poorly
      differentiated areas. This tumor was classified as neuroendocrine carcinoma in
      accordance with the 2010 World Health Organization classification of pancreatic
      endocrine neoplasms. He remains free of evidence of recurrence 2 years
      postsurgery. A review of published reports indicated that giant insulinomas are
      more malignant than smaller ones, and metastatic disease is found on presentation
      in 56% of patients with giant insulinomas; however, we were unable to identify
      any correlation between grade of pancreatic neuroendocrine tumor and biological
      behavior of giant insulinomas. CONCLUSIONS: Giant insulinomas more frequently
      exhibit malignant behavior, such as local invasion, lymph node involvement, and
      liver metastasis, than smaller ones. However, there was no relationship between
      grade and rate of metastases or survival in this small case series.
      Identification of useful biological markers is necessary.

PMID- 27864817
TI  - Surgical resection of recurrent gastrointestinal stromal tumor after interruption
      of long-term nilotinib therapy.
AB  - BACKGROUND: Nilotinib inhibits the tyrosine kinase activities of ABL1/BCR-ABL1,
      KIT, and platelet-derived growth factor receptors (PDGFRs). The results of a
      phase III clinical trial indicated that nilotinib could not be recommended for
      broad use as first-line therapy for gastrointestinal stromal tumor (GIST).
      However, some clinical studies have reported the effectiveness of nilotinib. We
      report here the cases of two patients who underwent surgical resections of
      nilotinib-resistant lesions after long-term nilotinib administration. CASE
      PRESENTATION: Two Japanese female patients, aged 66 and 70 years, experienced
      peritoneal recurrence of intestinal GIST several years after surgery. Both were
      registered in the ENESTg1 trial and received nilotinib therapy. Although they
      continued nilotinib administration with a partial response according to the
      protocol, nilotinib-resistant lesions, which were diagnosed as focally
      progressive disease, developed and complete surgical resection was performed.
      Pathological examination revealed that the tumors were composed of viable KIT
      positive spindle cells, and the recurrent tumors were diagnosed as nilotinib
      resistant GIST. In gene mutation analysis, a secondary KIT gene mutation was
      detected in one case. Both patients have survived more than 5 years after the
      first surgery. CONCLUSIONS: Of patients who were registered in this trial, we
      have encountered two patients with long-term effects after nilotinib
      administration. Moreover, secondary mutations in the KIT gene, similar to those
      involved in resistance to imatinib, might be involved in resistance to nilotinib.

PMID- 27864818
TI  - Effects of Thickness of a Low-Temperature Buffer and Impurity Incorporation on
      the Characteristics of Nitrogen-polar GaN.
AB  - In this study, effects of the thickness of a low temperature (LT) buffer and
      impurity incorporation on the characteristics of Nitrogen (N)-polar GaN are
      investigated. By using either a nitridation or thermal annealing step before the
      deposition of a LT buffer, three N-polar GaN samples with different thicknesses
      of LT buffer and different impurity incorporations are prepared. It is found that
      the sample with the thinnest LT buffer and a nitridation step proves to be the
      best in terms of a fewer impurity incorporations, strong PL intensity, fast
      mobility, small biaxial strain, and smooth surface. As the temperature increases
      at ~10 K, the apparent donor-acceptor-pair band is responsible for the decreasing
      integral intensity of the band-to-band emission peak. In addition, the thermal
      annealing of the sapphire substrates may cause more impurity incorporation around
      the HT-GaN/LT-GaN/sapphire interfacial regions, which in turn may result in a
      lower carrier mobility, larger biaxial strain, larger bandgap shift, and stronger
      yellow luminescence. By using a nitridation step, both a thinner LT buffer and
      less impurity incorporation are beneficial to obtaining a high quality N-polar
      GaN.

PMID- 27864820
TI  - Response to 'A functional mechanistic study of the effect of emollients on the
      structure and function of the skin barrier'.

PMID- 27864819
TI  - Can We Optimize Arc Discharge and Laser Ablation for Well-Controlled Carbon
      Nanotube Synthesis?
AB  - Although many methods have been documented for carbon nanotube (CNT) synthesis,
      still, we notice many arguments, criticisms, and appeals for its optimization and
      process control. Industrial grade CNT production is urgent such that invention of
      novel methods and engineering principles for large-scale synthesis are needed.
      Here, we comprehensively review arc discharge (AD) and laser ablation (LA)
      methods with highlighted features for CNT production. We also display the growth
      mechanisms of CNT with reasonable grassroots knowledge to make the synthesis more
      efficient. We postulate the latest developments in engineering carbon feedstock,
      catalysts, and temperature cum other minor reaction parameters to optimize the
      CNT yield with desired diameter and chirality. The rate limiting steps of AD and
      LA are highlighted because of their direct role in tuning the growth process.
      Future roadmap towards the exploration of CNT synthesis methods is also outlined.

PMID- 27864821
TI  - Effect of alterations in apoptotic pathway on development of metabolic syndrome
      in patients with psoriasis vulgaris.
AB  - BACKGROUND: An increase in the incidence of metabolic syndrome (MetS) has been
      identified in patients with psoriasis. OBJECTIVES: To evaluate the role of
      changes in expression of apoptosis activators [B-cell lymphoma (Bcl)-2-like
      protein 4 (BAX), cytochrome c (cytC) and caspase-3 (CASP3)] and apoptosis
      inhibitors [Bcl-2, survivin, cyclin D1 (CCND1), superoxide dismutase (SOD),
      catalase 3 (CAT), glutathione synthetase (GS), heat shock protein (Hsp)27, Hsp60,
      Hsp70 and Hsp90] on development of MetS in patients with psoriasis vulgaris.
      METHODS: Fifty patients with psoriasis were enrolled; 25 had MetS. Twenty-five
      healthy people and 25 people with only MetS were included as a control group.
      Serum fasting blood glucose, urea, creatinine, total cholesterol, high-density
      lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides,
      thyroid-stimulating hormone, fraction of thyroxine, fasting insulin and highly
      sensitive C-reactive protein levels were measured. Expression of BAX, cytC,
      CASP3, Bcl-2, survivin, CCND1, SOD, CAT, GS, and Hsp27, Hsp60, Hsp70 and Hsp90
      were measured in peripheral blood. Clinical activation of patients with psoriasis
      was calculated using Psoriasis Area and Severity Index scores. RESULTS: In
      patients with MetS there was an increase in expression of genes for cytC,
      survivin and Hsp27, Hsp60 and Hsp90, and a decrease in expression of CCND1.
      Furthermore, expression levels of CCND1 were identified to be an independent risk
      factor for MetS development in patients with psoriasis. CONCLUSIONS: The increase
      in expression of survivin and Hsp27, Hsp60 and Hsp90, and the decrease in CCND1
      expression may be important mechanisms in the development of MetS in patients
      with psoriasis.

PMID- 27864822
TI  - Caregiver-directed home-based intensive bimanual training in young children with
      unilateral spastic cerebral palsy: a randomized trial.
AB  - AIM: To examine the efficacy of caregiver-directed, home-based intensive bimanual
      training in children with unilateral spastic cerebral palsy (USCP) using a
      randomized control trial. METHOD: Twenty-four children (ages 2y 6mo-10y 1mo; 10
      males, 14 females) performed home-based activities directed by a caregiver for 2
      hours per day, 5 days per week, for 9 weeks (total=90h). Cohorts of children were
      age-matched into groups and randomized to receive home-based hand-arm bimanual
      intensive therapy (H-HABIT; n=12) or lower-limb functional intensive training
      (LIFT-control; n=12). Caregivers were trained before the intervention and
      supervised remotely via telerehabilitation. Dexterity and bimanual hand function
      were assessed using the Box and Blocks test (BBT) and the Assisting Hand
      Assessment (AHA) respectively. Caregiver perception of functional goals was
      measured using the Canadian Occupational Performance Measure (COPM). RESULTS: H
      HABIT showed greater improvement on the BBT compared to LIFT-control and no
      improvement on the AHA. H-HABIT demonstrated significant improvement in COPM
      Performance compared to LIFT-control and both groups showed equal improvement in
      COPM-Satisfaction. INTERPRETATION: H-HABIT improved dexterity and performance of
      functional goals, but not bimanual performance, in children with USCP compared to
      a control group receiving intervention of equal intensity/duration that also
      controlled for increased caregiver attention. Home-based models provide a
      valuable, family-centered approach to achieve increased treatment intensity.

PMID- 27864823
TI  - Aberrant mTOR signaling and disrupted autophagy: The missing link in potential
      vigabatrin-associated ocular toxicity?
AB  - Vigabatrin (VGB; gamma-vinylGABA) is a unique antiepileptic directly elevating
      CNS GABA via inactivation of the GABA metabolic enzyme GABA-transaminase. VGB is
      effective in treating infantile spasms, a rare seizure disorder associated with
      significant morbidity. The potential for unexplained bilateral constriction of
      the visual field associated with VGB intervention can severely limit its temporal
      utility. Removal of this potential adverse effect with adjuvant intervention(s)
      would represent a significant advance in epilepsy therapeutics.

PMID- 27864824
TI  - Successful treatment of ustekinumab in a psoriasis patient with human T-cell
      leukemia/lymphotropic virus type 1 infection.

PMID- 27864825
TI  - Individual hippocampal subfield assessment indicates that matrix macromolecules
      and gliosis are key elements for the increased T2 relaxation time seen in
      temporal lobe epilepsy.
AB  - OBJECTIVE: Increased T2 relaxation time is often seen in temporal lobe epilepsy
      (TLE) with hippocampal sclerosis. Water content directly affects the effective T2
      in a voxel. Our aim was to evaluate the relation between T2 values and two
      molecules associated with brain water homeostasis aquaporin 4 (AQP4) and
      chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the
      hippocampal region of patients with TLE. METHODS: Hippocampal T2 imaging and
      diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with
      TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex
      vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy
      control hippocampi (histologic and radiologic controls, HRCs), and each
      hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC
      controls were submitted to immunohistochemistry for neurons (neuron nuclei
      [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated
      microglia (human leukocyte antigen-D-related [HLA-DR]), polarized AQP4, and CSPG.
      RESULTS: Patients with TLE had higher in vivo and ex vivo hippocampal T2
      relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher
      gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In
      vivo relaxation correlated with astrogliosis in the subiculum and extracellular
      CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the
      hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between
      in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with
      the immunopositive area for CSPG in the hilus. SIGNIFICANCE: Our data indicate
      that astrogliosis, microgliosis, and CSPG expression correlate with the increased
      T2 relaxation time seen in the hippocampi of patients with TLE.

PMID- 27864826
TI  - Dietary intervention in the dystopian world of severe mental illness: measure for
      measure, then manage.

PMID- 27864828
TI  - Maternal Na+ intake induces renal function injury in rats prevented by a short
      term angiotensin converting enzyme inhibitor.
AB  - The Na+ -ATPase, a secondary pump in the proximal tubule, is only weakly
      responsive to angiotensin II in adult offspring exposed perinatally to high Na+
      intake. We have investigated whether the offspring from mothers given 0.3 mol/L
      NaCl show an ineffective angiotensin II action to increase in blood pressure. It
      was hypothesized that functional alterations at adult life are associated with
      the number of angiotensin II-positive cells in the developing kidney, with
      increased oxidative stress in maternal/foetal organs, or with morphometrical
      changes in placentas. Wistar female rats were maintained on 0.3 mol/L NaCl in
      their drinking water from 20 days before conception until weaning. After weaning,
      some of the male offspring were treated with enalapril for 21 days. Glomerular
      filtration rate was recorded up to 210 days of age, when mean arterial pressure
      was measured after infusion of angiotensin II. To investigate the placenta and
      foetal kidneys, mothers on tap water or NaCl were also treated with alpha
      tocopherol, pregnancy being interrupted on the 20th day. There were no changes in
      the number of cells positive for angiotensin II in the foetal kidney and
      unchanged lipid peroxidation in the placenta of offspring exposed to NaCl, but
      the intermediate trophoblast area in the junctional zone was increased, possibly
      reducing maternal-foetal exchange. Glomerular filtration rate was reduced and
      there was an attenuated effect of angiotensin II on elevation of blood pressure,
      which could be mediated by an elevated angiotensin II during early life, once
      these disturbances had been prevented by early and short-term treatment with
      enalapril.

PMID- 27864830
TI  - Risk of psychiatric disorders, self-harm behaviour and service use associated
      with bariatric surgery.
AB  - OBJECTIVE: To investigate psychiatric outcomes after bariatric surgery, including
      suicide, self-harm, psychiatric service use and substance misuse. METHOD:
      Retrospective study on a Danish nationwide register-based cohort of 22 451
      patients followed for 1 029 736 person-years. Data were analysed utilizing single
      and multi-event Cox regression with non-operated controls with obesity and
      mirror-image analyses with the operated patient serving as their own controls.
      RESULTS: We showed an increased ratio of self-harm (hazard ratio [HR] 3.23, P <
      0.001; incidence rate ratio [IRR] 1.71, P < 0.001), psychiatric service use
      (admissions IRR 1.52, P < 0.001; emergency room visits IRR 1.70, P < 0.001),
      psychiatric diagnosis (organic psychiatric disorders HR 1.78, P < 0.001;
      substance use HR 2.06, P < 0.001; mood disorders HR 2.66, P < 0.001; neurotic,
      stress-related and somatoform disorders HR 2.48, P < 0.001; behavioural syndromes
      HR 3.15, P < 0.001; disorders of personality HR 2.68, P < 0.001; behavioural and
      emotional disorders HR 6.43, P < 0.001), as well as substance misuse utilizing
      Cox regression as well as mirror-image analyses, as compared to non-operated. We
      did not find an increased suicide rate (HR 1.35, P = 0.658) among operated as
      compared to non-operated. CONCLUSION: Our study shows that undergoing bariatric
      surgery is associated with increases in self-harm, psychiatric service use and
      occurrence of mental disorders.

PMID- 27864827
TI  - Biomarkers of oxidative and nitro-oxidative stress: conventional and novel
      approaches.
AB  - : The concept of oxidative stress (OS) that connects altered redox biology with
      various diseases was introduced 30 years ago and has generated intensive research
      over the past two decades. Whereas it is now commonly accepted that macromolecule
      oxidation in response to ROS is associated with a variety of pathologies, the
      emergence of NO as a key regulator of redox signalling has led to the discovery
      of the pathophysiological significance of reactive nitrogen species (RNS). RNS
      can elicit various modifications of macromolecules and lead to nitrative or nitro
      OS. In order to investigate oxidative and nitro-OS in human and in live animal
      models, circulating biomarker assays have been developed. This article provides
      an overview of key biomarkers used to assess lipid peroxidation and NO/NO2
      signalling, thereby stressing the necessity to analyse several OS biomarkers in
      relation to the overall (aerobic) metabolism and health condition of patients. In
      addition, the potential interest of heart rate variability as the non-invasive
      integrative biomarker of OS is discussed. LINKED ARTICLES: This article is part
      of a themed section on Redox Biology and Oxidative Stress in Health and Disease.
      To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.

PMID- 27864831
TI  - Alveolar bone in human immunodeficiency virus infection: is it changed by long
      term antiretroviral therapy?
AB  - BACKGROUND: Previous studies have reported that human immunodeficiency virus
      (HIV) infection and antiretroviral therapy (ART) can lead to osteoporosis in HIV
      infected individuals. However, their effects on alveolar bone are not well
      established. The objective of this study was to measure the alveolar bone mineral
      density (BMD) of HIV-infected patients, with and without antiretroviral therapy
      (ART), in comparison with that of HIV-free individuals, and to determine factors
      associated with the BMD of alveolar bone. METHODS: A cross-sectional study was
      performed in non-HIV-infected individuals and HIV-infected individuals, with and
      without ART. Medical status and clinical data were recorded. Periapical
      radiographs of maxillary and mandibular right premolars were analysed for changes
      of alveolar BMD based on HIV/ART status. Other factors associated with the
      changes of alveolar BMD were explored using a parametric multivariate analysis of
      covariance (MANCOVA). RESULTS: One-hundred and one HIV-infected individuals
      receiving ART (age range: 23-57 years; median age 39 years), 58 receiving no ART
      (age range: 20-59 years; median age 34 years) and 50 HIV-negative individuals
      (age range: 19-59 years; median age 36 years) were enrolled. Neither HIV status
      nor use of ART was significantly associated with the changes of alveolar BMD.
      CONCLUSION: Although osteoporosis has been reported in HIV-infected individuals
      treated with ART, alveolar BMD does not appear to be changed as a result of the
      infection, or use of ART.

PMID- 27864829
TI  - Pediatric case of anaplastic lymphoma kinase-positive anaplastic large cell
      lymphoma forming a solitary skin tumor on the forearm.
AB  - A 5-year-old girl noticed a rapidly growing reddish nodule on her right forearm.
      Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged.
      Skin biopsy revealed excessive infiltration of atypical neoplastic cells
      expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and
      immunohistochemical findings were consistent with anaplastic large cell lymphoma
      (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node
      biopsy and bone marrow examination did not show any evidence of systemic
      dissemination. However, due to the positive results for ALK and multiple
      lymphadenopathy, we diagnosed ALK-positive ALCL forming a solitary skin tumor on
      the forearm. The patient received chemotherapy and presented marked improvement.
      This paper discusses the difficulty of diagnosing pediatric ALK-positive ALCL
      limited to the skin and reviews the medical published work.

PMID- 27864832
TI  - Colistin Reduces LPS-Triggered Inflammation in a Human Sepsis Model In Vivo: A
      Randomized Controlled Trial.
AB  - The previously described anti-endotoxin effect of colistin has not been
      investigated in humans yet. We performed a randomized, double-blind, placebo
      controlled crossover trial to determine the degree of colistin-driven modulation
      of inflammatory response in blood of lipopolysaccharide (LPS)-challenged healthy
      volunteers in a human endotoxemia model. After a single intravenous dose of 2.5
      million IU colistin methanesulfonate, interleukin (IL)-6, IL-8, tumor necrosis
      factor alpha (TNF-alpha), and IL-1beta concentrations as well as other biomarkers
      of inflammation such as C-reactive protein, differential leukocyte counts, and
      body temperature were measured up to 24 h postdose. Colistin significantly
      decreased the inflammatory cytokine response to LPS in blood of healthy
      volunteers. This effect was most evident for IL-6, IL-8, and TNF-alpha. This
      study is the first to confirm the anti-endotoxin effect of colistin in humans in
      vivo. Further studies might increase our knowledge on the interaction between
      colistin and the effectors of the immune system.

PMID- 27864834
TI  - Case of metastatic uveal melanoma in which an antitumor effect appeared after
      ipilimumab discontinuation due to autoimmune hypophysitis.

PMID- 27864833
TI  - Structured clinical documentation in the electronic medical record to improve
      quality and to support practice-based research in epilepsy.
AB  - OBJECTIVE: Using the electronic medical record (EMR) to capture structured
      clinical data at the point of care would be a practical way to support quality
      improvement and practice-based research in epilepsy. METHODS: We describe our
      stepwise process for building structured clinical documentation support tools in
      the EMR that define best practices in epilepsy, and we describe how we
      incorporated these toolkits into our clinical workflow. RESULTS: These tools
      write notes and capture hundreds of fields of data including several score tests:
      Generalized Anxiety Disorder-7 items, Neurological Disorders Depression Inventory
      for Epilepsy, Epworth Sleepiness Scale, Quality of Life in Epilepsy-10 items,
      Montreal Cognitive Assessment/Short Test of Mental Status, and Medical Research
      Council Prognostic Index. The tools summarize brain imaging, blood laboratory,
      and electroencephalography results, and document neuromodulation treatments. The
      tools provide Best Practices Advisories and other clinical decision support when
      appropriate. The tools prompt enrollment in a DNA biobanking study. We have thus
      far enrolled 231 patients for initial visits and are starting our first annual
      follow-up visits and provide a brief description of our cohort. SIGNIFICANCE: We
      are sharing these EMR tools and captured data with other epilepsy clinics as part
      of a Neurology Practice Based Research Network, and are using the tools to
      conduct pragmatic trials using subgroup-based adaptive designs.

PMID- 27864835
TI  - Intrahepatic cholangiocarcinoma frequently shows loss of BAP1 and PBRM1
      expression, and demonstrates specific clinicopathological and genetic
      characteristics with BAP1 loss.
AB  - AIMS: BAP1 and PBRM1 expression loss has been observed in multiple cancers,
      including intrahepatic cholangiocarcinoma (ICC). We investigated BAP1 and PBRM1
      expression in ICC using immunohistochemistry, and analysed its association with
      clinicopathological and genetic features, including two histological subtypes.
      METHODS AND RESULTS: Whole-section slides of 108 consecutive primary ICC cases
      were immunostained against BAP1 and PBRM1. Complete loss of BAP1 and PBRM1 was
      observed in 21 (19.4%) and 25 (23.1%) cases, respectively, and partial loss was
      identified in four (3.7%) and nine (8.4%) cases. In all cases, normal bile ducts
      were strongly and diffusely positive for both BAP1 and PBRM1. ICC with BAP1 loss
      showed lower serum CA19-9 levels, less perineural invasion, rare mucin
      production, weaker immunoreactivity against S-100P and stronger immunoreactivity
      against N-cadherin and NCAM. IDH mutations were identified more frequently in
      ICCs with BAP1 loss. All ICC with BAP1 loss corresponded to small-duct type ICC.
      Multivariate Cox regression analysis showed that BAP1 loss was an independent
      prognostic factor for both overall and recurrence-free survival (P < 0.05).
      Conversely, PBRM1 loss was found in both small-duct type and large-duct type ICC,
      and was not associated significantly with any specific characteristics, including
      prognosis. CONCLUSION: BAP1 and PBRM1 loss is seen frequently in ICC. ICC with
      BAP1 loss shares features of small-duct type ICC.

PMID- 27864836
TI  - Choroidal and central foveal thickness in patients with scleroderma and its
      systemic associations.
AB  - BACKGROUND: The aim was to investigate the morphological changes in the fovea and
      choroid in patients with scleroderma and its systemic associations. METHODS:
      Thirty-four scleroderma patients and 31 healthy controls were enrolled. Choroidal
      thickness (CT) at five defined points (subfoveal [sfCT] and 1.0 [N1.0] and 3.0 um
      nasal [N3.0] and 1.0 [T1.0] and 3.0 um temporal [T3.0] from the centre of the
      fovea) and central foveal thickness were measured. RESULTS: The mean central
      foveal thickness (right eye 229.3 +/- 28.6 versus 232.6 +/- 29.7 and left eye
      219.8 +/- 21.4 versus 223.3 +/- 21.9 um) and sfCT (right eye 326.4 +/- 56.5
      versus 327.3 +/- 62.1 and left eye 316.7 +/- 53.4 versus 317.6 +/- 51.6 um)
      values were not different in patients with scleroderma compared with the controls
      (p > 0.05). The mean CT at N1.0, N3.0, T1.0 and T3.0 did not differ among these
      groups in both eyes (p > 0.05). There was no difference in the mean central
      foveal thickness and CT of both eyes in diffuse and limited scleroderma (p >
      0.05). A negative correlation was found between anti-nuclear antibody positivity
      and CT at T3 and N3 (respectively, r = -0.439 and r = -0.383, p < 0.05).
      CONCLUSION: Choroidal thickness at five points and central foveal thickness in
      both eyes did not significantly differ in scleroderma patients compared with
      healthy controls. Choroidal thickness at the T3 and N3 points showed a negative
      correlation with anti-nuclear antibody positivity.

PMID- 27864837
TI  - Risk factors for nonpurulent leg cellulitis: a systematic review and meta
      analysis.
AB  - Nonpurulent cellulitis is an acute bacterial infection of the dermal and
      subdermal tissues that is not associated with purulent drainage, discharge or
      abscess. The objectives of this systematic review and meta-analysis were to
      identify and appraise all controlled observational studies that have examined
      risk factors for the development of nonpurulent cellulitis of the leg (NPLC). A
      systematic literature search of electronic databases and grey literature sources
      was performed in July 2015. The Newcastle-Ottawa Scale (NOS) was used to assess
      methodological quality of included studies. Of 3059 potentially eligible studies
      retrieved and screened, six case-control studies were included. An increased risk
      of developing NPLC was associated with previous cellulitis [odds ratio (OR) 40.3,
      95% confidence interval (CI) 22.6-72.0], wound (OR 19.1, 95% CI 9.1-40.0),
      current leg ulcers (OR 13.7, 95% CI 7.9-23.6), lymphoedema/chronic leg oedema (OR
      6.8, 95% CI 3.5-13.3), excoriating skin diseases (OR 4.4, 95% CI 2.7-7.1), tinea
      pedis (OR 3.2, 95% CI 1.9-5.3) and body mass index > 30 kg m-2 (OR 2.4, 95% CI
      1.4-4.0). Diabetes, smoking and alcohol consumption were not associated with
      NPLC. Although diabetics may have been underrepresented in the included studies,
      local risk factors appear to play a more significant role in the development of
      NPLC than do systemic risk factors. Clinicians should consider the treatment of
      modifiable risk factors including leg oedema, wounds, ulcers, areas of skin
      breakdown and toe-web intertrigo while administering antibiotic treatment for
      NPLC.

PMID- 27864838
TI  - Preoperative alpha-blockade in phaeochromocytoma and paraganglioma: is it always
      necessary?
AB  - Resection of phaeochromocytoma and paraganglioma (PPGL) is traditionally preceded
      by alpha-blockade to prevent complications of haemodynamic instability
      intraoperatively. While there is general agreement on preoperative alpha-blockade
      for classic PPGLs presenting with hypertension, it is less clear whether alpha
      blockade is necessary in predominantly dopamine-secreting tumours, normotensive
      PPGLs, as well as tumours that appear to be biochemically 'silent'. Preoperative
      management of these 'atypical' PPGLs is challenging and the treatment approach
      must be individualized, carefully weighing the risk of intraoperative
      hypertension against the possibility of orthostatic and prolonged postoperative
      hypotension. Consideration of antihypertensive medication pharmacology in the
      light of catecholamine physiology and PPGL secretory profile will facilitate the
      formulation of individualized preoperative preparatory strategies.

PMID- 27864839
TI  - Reduction of the foreign body response and neuroprotection by apyrase and
      minocycline in chronic cannula implantation in the rat brain.
AB  - Implantation of electrodes or cannulae into the brain is accompanied by a tissue
      response referred to as foreign body response. Adenosine triphosphate (ATP) is
      one of the signalling molecules released by injured cells which mediate the
      chemoattraction of microglial cells. The constitutive release of pro-inflammatory
      and cytotoxic substances by microglial cells in chronic implants exacerbates
      neuronal cell death and the immune response. This study aimed to interfere with
      the initial events of the foreign body response in order to mitigate
      neurotoxicity and inflammation. For this purpose, the ATP-hydrolysing enzyme
      apyrase and the antibiotic minocycline with a broad range of anti-inflammatory,
      anti-apoptotic and glutamate-antagonist properties were locally infused during
      cannula implantation in the caudal forelimb area of the motor cortex in Lister
      Hooded rats. The rats' motor performance was assessed in a skilled reaching task
      and the distribution of neurons and glial cells in the vicinity of the implant
      was examined 2 and 6 weeks post-implantation. Apyrase as well as minocycline
      increased the number of surviving neurons and reduced microglial activation.
      Moreover, minocycline improved the motor performance and, additionally, caused a
      temporary reduction in astrogliosis, suggesting it as a possible therapeutic
      candidate to improve the biocompatibility of chronic brain implants.

PMID- 27864840
TI  - Ectopic respiratory mucosa in the skin which showed the repetitive distribution
      of ciliated bronchogenic epithelia and squamous metaplasia.

PMID- 27864841
TI  - Clinical factors predicting the therapeutic response to ustekinumab in patients
      with moderate to severe chronic plaque psoriasis.
AB  - While ustekinumab has been widely used as an effective biologic for the treatment
      of chronic plaque psoriasis, no prospective studies have specifically
      investigated the clinical factors that may influence treatment outcomes with
      ustekinumab. This post-hoc analysis aimed to identify specific clinical factors
      that may influence treatment outcomes with ustekinumab in psoriasis patients. In
      the MARCOPOLO study, 102 Korean patients with moderate to severe psoriasis were
      analyzed to assess the influence of baseline characteristics as clinical factors
      on clinical response (improvement in Psoriasis Area and Severity Index by
      >=75%/90% [PASI75/PASI90]) to ustekinumab. In addition, differences in PASI75 and
      PASI90 responses between the responder group and non-responders were evaluated at
      weeks 28 and 52. Multiple logistic regression analysis was used to determine
      adjusted clinical factors predicting treatment outcomes among patient
      characteristics. At week 28, there was a significant difference in PASI75/PASI90
      response based on prior biologic experience, although the difference did not
      persist at week 52. In addition, after adjusting for the effects of relevant
      clinical factors, biologic experience was significantly associated with less
      PASI75 (odds ratio [OR] = 0.14, P = 0.001) and PASI90 (OR = 0.22, P = 0.036)
      responses at week 28. The presence of comorbidities was higher among non
      responders than among PASI75/PASI90 responders at both weeks 28 and 52, but was
      not statistically significant. Previous biologic use was the only clinical factor
      predicting less response at week 28, although it did not influence the clinical
      response after week 52. Further studies are warranted to investigate the
      association between presence of comorbidities and clinical response.

PMID- 27864842
TI  - Elevation of serum carcinoembryonic antigen in a case of cholinergic urticaria
      with failed detection of hypohidrosis by the conventional starch-iodine test.

PMID- 27864843
TI  - Measurement of caffeine and its three primary metabolites in human plasma by HPLC
      ESI-MS/MS and clinical application.
AB  - Caffeine is a mild stimulant with significant potential for abuse, being consumed
      in larger doses with the widespread availability of energy drinks and by novel
      routes of administration such as inspired powder, oral sprays and electronic
      cigarettes. How these recent changes in caffeine consumption affecting caffeine
      disposition and abuse potential is of growing concern. In the study of caffeine
      disposition in humans, it is common to only measure the caffeine concentration;
      however, caffeine's three major metabolites (paraxanthine, theobromine and
      theophylline) retain central nervous system stimulant activity that may
      contribute to the overall pharmacological activity and toxicity. Therefore, it
      would be scientifically more rigorous to measure caffeine and its major
      metabolites in the evaluation of caffeine disposition in human subjects. Herein,
      we report a method for the simultaneous quantification of caffeine and its three
      major metabolites in human plasma by high-performance liquid chromatography
      coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma
      samples were treated by simple protein precipitation and the analytes were
      separated using a 6 min gradient program. Precision and accuracy were well within
      in the 15% acceptance range. The simple sample preparation, short runtime,
      sensitivity and the inclusion of caffeine's major metabolites make this assay
      methodology optimal for the study of caffeine's pharmacokinetics and
      pharmacodynamics in human subjects.

PMID- 27864844
TI  - Pyogenic granuloma possibly associated with capecitabine therapy.

PMID- 27864845
TI  - Activity of the anticonvulsant lacosamide in experimental and human epilepsy via
      selective effects on slow Na+ channel inactivation.
AB  - OBJECTIVE: In human epilepsy, pharmacoresistance to antiepileptic drug therapy is
      a major problem affecting ~30% of patients with epilepsy. Many classical
      antiepileptic drugs target voltage-gated sodium channels, and their potent
      activity in inhibiting high-frequency firing has been attributed to their strong
      use-dependent blocking action. In chronic epilepsy, a loss of use-dependent block
      has emerged as a potential cellular mechanism of pharmacoresistance for
      anticonvulsants acting on voltage-gated sodium channels. The anticonvulsant drug
      lacosamide (LCM) also targets sodium channels, but has been shown to
      preferentially affect sodium channel slow inactivation processes, in contrast to
      most other anticonvulsants. METHODS: We used whole-cell voltage clamp recordings
      in acutely isolated cells to investigate the effects of LCM on transient Na+
      currents. Furthermore, we used whole-cell current clamp recordings to assess
      effects on repetitive action potential firing in hippocampal slices. RESULTS: We
      show here that LCM exerts its effects primarily via shifting the slow
      inactivation voltage dependence to more hyperpolarized potentials in hippocampal
      dentate granule cells from control and epileptic rats, and from patients with
      epilepsy. It is important to note that this activity of LCM was maintained in
      chronic experimental and human epilepsy. Furthermore, we demonstrate that the
      efficacy of LCM in inhibiting high-frequency firing is undiminished in chronic
      experimental and human epilepsy. SIGNIFICANCE: Taken together, these results show
      that LCM exhibits maintained efficacy in chronic epilepsy, in contrast to
      conventional use-dependent sodium channel blockers such as carbamazepine. They
      also establish that targeting slow inactivation may be a promising strategy for
      overcoming target mechanisms of pharmacoresistance.

PMID- 27864846
TI  - Monochorial diamniotic dizygotic twins in a German Shepherd Dog: A case report.
AB  - CASE REPORT: A 6.5-year-old clinically healthy German Shepherd Dog with regular
      oestrous cycles of 6 months was presented for pregnancy diagnosis on day 38 after
      ovulation (p.ov.). Ultrasonography revealed three individual placental sites in
      progressed resorption and two vital adequately developed foetuses sharing a joint
      placenta. On days 41 and 48 p.ov., sonographic signs indicated normal development
      of both foetuses, but on day 52 p.ov., both foetuses were found to be dead. A
      caesarean section was performed the same day. Examination of the removed uterus
      confirmed the diagnosis of a "twin" pregnancy with two foetuses sharing the same
      placental site but separate amniotic membranes. One foetus showed generalized
      oedema (anasarca). Bacterial culture of swabs taken from inside the placental
      cavity was negative. At histological examination of the uterus, no signs of
      inflammation were found. Serum relaxin concentrations (day 38, 41, 48 and 52.
      p.ov.) were consistent with those of bitches with normal pregnancies. Cytogenetic
      analysis of the two foetuses revealed dizygotic twins, one male and one female
      according to SRY-PCR. By genotyping 17 high-polymorphic canine microsatellites,
      it could be demonstrated that the two foetuses developed from two different
      oocytes.

PMID- 27864847
TI  - Diagnostic Targeted Resequencing in 349 Patients with Drug-Resistant Pediatric
      Epilepsies Identifies Causative Mutations in 30 Different Genes.
AB  - Targeted resequencing gene panels are used in the diagnostic setting to identify
      gene defects in epilepsy. We performed targeted resequencing using a 30-genes
      panel and a 95-genes panel in 349 patients with drug-resistant epilepsies
      beginning in the first years of life. We identified 71 pathogenic variants, 42 of
      which novel, in 30 genes, corresponding to 20.3% of the probands. In 66% of
      mutation positive patients, epilepsy onset occurred before the age of 6 months.
      The 95-genes panel allowed a genetic diagnosis in 22 (6.3%) patients that would
      have otherwise been missed using the 30-gene panel. About 50% of mutations were
      identified in genes coding for sodium and potassium channel components. SCN2A was
      the most frequently mutated gene followed by SCN1A, KCNQ2, STXBP1, SCN8A, CDKL5,
      and MECP2. Twenty-nine mutations were identified in 23 additional genes, most of
      them recently associated with epilepsy. Our data show that panels targeting about
      100 genes represent the best cost-effective diagnostic option in pediatric drug
      resistant epilepsies. They enable molecular diagnosis of atypical phenotypes,
      allowing to broaden phenotype-genotype correlations. Molecular diagnosis might
      influence patients' management and translate into better and specific treatment
      recommendations in some conditions.

PMID- 27864848
TI  - Age-related small vessel disease: a potential contributor to neurodegeneration in
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the
      central nervous system wherein, after an initial phase of transient neurological
      defects, slow neurological deterioration due to progressive neuronal loss ensues.
      Age is a major determinant of MS progression onset and disability. Over the past
      years, several mechanisms have been proposed to explain the key drivers of
      neurodegeneration and disability accumulation in MS. However, the effect of
      commonly encountered age-related cerebral vessel disease, namely small vessel
      disease (SVD), has been largely neglected and constitutes the aim of this review.
      SVD shares some features with MS, that is, white matter demyelination and brain
      atrophy, and has been shown to contribute to the neuronal damage seen in vascular
      cognitive impairment. Several lines of evidence suggest that an interaction
      between MS and SVD may influence MS-related neurodegeneration. SVD may contribute
      to hypoperfusion, reduced vascular reactivity and tissue hypoxia, features seen
      in MS. Venule and endothelium abnormalities have been documented in MS but the
      role of arterioles and of other neurovascular unit structures, such as the
      pericyte, has not been explored. Vascular risk factors (VRF) have recently been
      associated with faster progression in MS, though the mechanisms are unclear since
      very few studies have addressed the impact of VRF and SVD on MS imaging and
      pathology outcomes. Therapeutic agents targeting the microvasculature and the
      neurovascular unit may impact both SVD and MS and may benefit patients with dual
      pathology.

PMID- 27864849
TI  - Impact of plant growth-promoting rhizobacteria on root colonization potential and
      life cycle of Rhizophagus irregularis following co-entrapment into alginate
      beads.
AB  - AIMS: This study aimed at evaluating the impact of seven plant growth-promoting
      rhizobacteria (PGPR) on root colonization and life cycle of Rhizophagus
      irregularis MUCL 41833 when co-entrapped in alginate beads. METHODS AND RESULTS:
      Two in vitro experiments were conducted. The first consisted of the
      immobilization of R. irregularis and seven PGPR isolates into alginate beads to
      assess the effect of the bacteria on the pre-symbiotic growth of the fungus. In
      the second experiment, the best performing PGPR from experiment 1 was tested for
      its ability to promote the symbiotic development of the AMF in potato plantlets
      from three cultivars. Results showed that only one isolate identified as
      Pseudomonas plecoglossicida (R-67094) promoted germ tube elongation and hyphal
      branching of germinated spores during the pre-symbiotic phase of the fungus. This
      PGPR further promoted the symbiotic development of the AMF in potato plants.
      CONCLUSIONS: The co-entrapment of Ps. plecoglossicida R-67094 and R. irregularis
      MUCL 41833 in alginate beads improved root colonization by the AMF and its
      further life cycle under the experimental conditions. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Co-entrapment of suitable AMF-PGPR combinations within alginate beads
      may represent an innovative technology that can be fine-tuned for the development
      of efficient consortia-based bioformulations.

PMID- 27864851
TI  - Letter to the editor - HPV vaccine and autoimmunity Incidence of new-onset
      autoimmune disease in girls and women with pre-existing autoimmune disease after
      quadrivalent human papillomavirus vaccination: a cohort study.

PMID- 27864850
TI  - Hyperhomocysteinemia in Greyhounds and its Association with Hypofolatemia and
      Other Clinicopathologic Variables.
AB  - BACKGROUND: Folate and cobalamin are essential cofactors for homocysteine (HCY)
      metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B
      vitamin deficiency and is associated with increased risk of cardiovascular
      disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases
      in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected
      chronic enteropathy. OBJECTIVES: To evaluate the frequencies of and the
      association between hypofolatemia and hyperhomocysteinemia in Greyhounds.
      ANIMALS: Data and serum samples from 559 Greyhounds. METHODS: Nested case-control
      study. The frequency of hypofolatemia in Greyhounds was determined by a
      laboratory database search. The relationship between hyperhomocysteinemia
      (measured by gas chromatography-mass spectrometry) and hypocobalaminemia and
      hypofolatemia was evaluated, and its frequency compared between healthy
      Greyhounds and Greyhounds with thrombosis or chronic diarrhea. RESULTS:
      Hypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common
      in hypo- than in normocobalaminemic dogs (49% vs. 35%; P = .0064).
      Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more
      common in hypo- than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy
      Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of
      those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were
      inversely correlated with serum folate concentration (rho = -0.28; P = .0386) and
      were positively associated with serum albumin concentration (rho = 0.66; P =
      .0022). CONCLUSIONS AND CLINICAL RELEVANCE: Hyperhomocysteinemia occurs
      frequently in the Greyhound population. Its association with hypofolatemia
      suggests decreased intracellular availability of B vitamins, but the functional
      implications warrant further investigation. Hyperhomocysteinemia in Greyhounds
      potentially may serve as a spontaneous canine model to further investigate
      hyperhomocysteinemia in humans.

PMID- 27864854
TI  - IgG4-related hypophysitis is highly prevalent among cases of histologically
      confirmed hypophysitis.
AB  - IgG4-related disease is an immune-mediated disease with manifestations in most
      organ systems among them the pituitary gland. To date, few cases of
      histologically confirmed cases of IgG-related hypophysitis have been reported.
      The aim of this study was to retrospectively determine the prevalence of IgG4
      related hypophysitis among cases previously diagnosed as primary hypophysitis
      (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not
      otherwise specified). Histological and immunohistochemical analysis revealed that
      12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the
      criteria for IgG4-related disease and, thus, IgG4-related hypophysitis should
      always be considered in the differential diagnosis of primary hypophysitis. All
      cases of IgG4-related hypophysitis showed a dense lymphoplasmacytic infiltrate
      with more than 10 IgG4-positive cells per high power field and a ratio of
      IgG4/IgG-positive cells of more than 40%, whereas storiform fibrosis was an
      inconsistent histological feature and was also seen in few cases of non-IgG
      related hypophysitis, thus lacking sensitivity and specificity. Obliterative
      phlebitis was not seen in any case. Thus, histological criteria defined for IgG4
      related disease in other organs should be modified for IgG4-related hypophysitis,
      accordingly.

PMID- 27864853
TI  - PET radiotracer development for imaging high-affinity state of dopamine D2 and D3
      receptors: Binding studies of fluorine-18 labeled aminotetralins in rodents.
AB  - Imaging the high-affinity, functional state (HA) of dopamine D2 and D3 receptors
      has been pursued in PET imaging studies of various brain functions. We report
      further evaluation of 18 F-5-OH-FPPAT, and the newer 18 F-5-OH-FHXPAT and 18 F-7
      OH-FHXPAT. Syntheses of 18 F-5-OH-FHXPAT and 18 F-7-OH-FHXPAT were improved by
      modifications of our previously reported procedures. Brain slices and brain
      homogenates from male Sprague-Dawley rats were used with the 3 radiotracers (74
      111 kBq/cc). Competition with dopamine (1-100 nM) and Gpp(NH)p (10-50 uM) were
      carried out to demonstrate binding to dopamine D2 and D3 HA-states and binding
      kinetics of 18 F-5-OH-FPPAT measured. Ex vivo brain slice autoradiography was
      carried out on rats administered with 18 F-5-OH-FHXPAT to ascertain HA-state
      binding. PET/CT imaging in rats and wild type (WT) and D2 knock-out mice were
      carried out using 18 F-7-OH-FHXPAT (2-37 MBq). Striatum was clearly visualized by
      the three radiotracers in brain slices and dopamine displaced more than 80% of
      binding, with dissociation rate in homogenates of 2.2 * 10-2 min-1 for 18 F-5-OH
      FPPAT. Treatment with Gpp(NH)p significantly reduced 50-80% striatal binding with
      faster dissociation rates (5.0 * 10-2 min-1 ), suggesting HA-state binding of 18
      F-5-OH-FPPAT and 18 F-5-OH-FHXPAT. Striatal binding of 18 F-5-OH-FHXPAT in ex
      vivo brain slices were sensitive to Gpp(NH)p, suggesting HA-state binding in
      vivo. PET binding ratios of 18 F-7-OH-FHXPAT in rat brain were ventral
      striatum/cerebellum = 2.09 and dorsal striatum/cerebellum = 1.65; similar binding
      ratios were found in the D2 WT mice. These results suggest that in vivo PET
      measures of agonists in the brain at least in part reflect binding to the
      membrane-bound HA-state of the dopamine receptor.

PMID- 27864852
TI  - H+ -pyrophosphatase IbVP1 promotes efficient iron use in sweet potato [Ipomoea
      batatas (L.) Lam.].
AB  - Iron (Fe) deficiency is one of the most common micronutrient deficiencies
      limiting crop production globally, especially in arid regions because of
      decreased availability of iron in alkaline soils. Sweet potato [Ipomoea batatas
      (L.) Lam.] grows well in arid regions and is tolerant to Fe deficiency. Here, we
      report that the transcription of type I H+ -pyrophosphatase (H+ -PPase) gene
      IbVP1 in sweet potato plants was strongly induced by Fe deficiency and auxin in
      hydroponics, improving Fe acquisition via increased rhizosphere acidification and
      auxin regulation. When overexpressed, transgenic plants show higher pyrophosphate
      hydrolysis and plasma membrane H+ -ATPase activity compared with the wild type,
      leading to increased rhizosphere acidification. The IbVP1-overexpressing plants
      showed better growth, including enlarged root systems, under Fe-sufficient or Fe
      deficient conditions. Increased ferric precipitation and ferric chelate reductase
      activity in the roots of transgenic lines indicate improved iron uptake, which is
      also confirmed by increased Fe content and up-regulation of Fe uptake genes, e.g.
      FRO2, IRT1 and FIT. Carbohydrate metabolism is significantly affected in the
      transgenic lines, showing increased sugar and starch content associated with the
      increased expression of AGPase and SUT1 genes and the decrease in beta-amylase
      gene expression. Improved antioxidant capacities were also detected in the
      transgenic plants, which showed reduced H2 O2 accumulation associated with up
      regulated ROS-scavenging activity. Therefore, H+ -PPase plays a key role in the
      response to Fe deficiency by sweet potato and effectively improves the Fe
      acquisition by overexpressing IbVP1 in crops cultivated in micronutrient
      deficient soils.

PMID- 27864855
TI  - Planar PtPd3 Complexes Stabilized by Three Bridging Silylene Ligands.
AB  - A heterobimetallic PtPd3 complex supported by three bridging diphenylsilylene
      ligands, [Pt{Pd(dmpe)}3 (MU3 -SiPh2 )3 ] (1, dmpe=1,2
      bis(dimethylphosphino)ethane), has been synthesized from mononuclear Pd and Pt
      complexes. The hexagonal core composed of Pt, Pd, and Si atoms is slightly larger
      than that of the tetrapalladium complex, [Pd{Pd(dmpe)}3 (MU3 -SiPh2 )3 ] (2).
      Reaction of PhSiH3 with complex 1 in the presence and absence of Ph2 SiH2 results
      in the formation of a tetranuclear complex with silyl and hydride ligands at the
      Pt center, [PtH(SiPh2 H){Pd(dmpe)}3 (MU3 -SiHPh)3 ] (3), and an octanuclear
      complex, [{Pt{Pd(dmpe)}3 (MU3 -SiHPh)3 }2 (kappa2 -dmpe)] (5), respectively. Both
      M-Si (M=Pt, Pd) bond lengths and the 29 Si NMR chemical shifts of 1 and 2 are
      located between those of mononuclear late transition-metal complexes with a
      silylene ligand and complexes with donor-stabilized silylene ligands. CuI and AgI
      adducts of 1 and 2, formulated as [M(MU-M'I){Pd(dmpe)}3 (MU3 -SiPh2 )3 ] (M=Pt,
      Pd; M'=Cu, Ag), undergo elimination of CuI (AgI) and regenerate the tetrametallic
      complexes upon heating or addition of a chelating diphosphine. Elimination of AgI
      from 2-AgI occurs more rapidly than elimination of CuI from 2-CuI, as determined
      from the results of kinetics experiments.

PMID- 27864856
TI  - Capturing differences in dental training using a virtual reality simulator.
AB  - Virtual reality simulators are becoming increasingly popular in dental schools
      across the world. But to what extent do these systems reflect actual dental
      ability? Addressing this question of construct validity is a fundamental step
      that is necessary before these systems can be fully integrated into a dental
      school's curriculum. In this study, we examined the sensitivity of the Simodont
      (a haptic virtual reality dental simulator) to differences in dental training
      experience. Two hundred and eighty-nine participants, with 1 (n = 92), 3 (n =
      79), 4 (n = 57) and 5 (n = 61) years of dental training, performed a series of
      tasks upon their first exposure to the simulator. We found statistically
      significant differences between novice (Year 1) and experienced dental trainees
      (operationalised as 3 or more years of training), but no differences between
      performance of experienced trainees with varying levels of experience. This work
      represents a crucial first step in understanding the value of haptic virtual
      reality simulators in dental education.

PMID- 27864857
TI  - Protein SUMOylation is Involved in Cell-cycle Progression and Cell Morphology in
      Giardia lamblia.
AB  - The unicellular protozoa Giardia lamblia is a food- and waterborne parasite that
      causes giardiasis. This illness is manifested as acute and self-limited diarrhea
      and can evolve to long-term complications. Successful establishment of infection
      by Giardia trophozoites requires adhesion to host cells and colonization of the
      small intestine, where parasites multiply by mitotic division. The tight binding
      of trophozoites to host cells occurs by means of the ventral adhesive disc, a
      spiral array of microtubules and associated proteins such as giardins. In this
      work we show that knock down of the Small Ubiquitin-like MOdifier (SUMO) results
      in less adhesive trophzoites, decreased cell proliferation and deep morphological
      alterations, including at the ventral disc. Consistent with the reduced
      proliferation, SUMO knocked-down trophozoites were arrested in G1 and in S phases
      of the cell cycle. Mass spectrometry analysis of anti-SUMO immunoprecipitates was
      performed to identify SUMO substrates possibly involved in these events. Among
      the identified SUMOylation targets, alpha-tubulin was further validated by
      Western blot and confirmed to be a SUMO target in Giardia trophozoites.

PMID- 27864858
TI  - Authors' response: Letter to the Editor - HPV vaccine and autoimmunity.

PMID- 27864859
TI  - Roles and competences for educators of undergraduate dental students: a
      discussion paper.
AB  - INTRODUCTION: Dental educators are important people who contribute to the
      development of every aspect of dental education. In part due to the lack of
      understanding of their roles and competences, dental educator development has so
      far received little consideration. With the aim of enhancing the dental
      profession's contribution to the development of undergraduate dental education,
      this article explores common roles of educators of undergraduate dental students
      and the competences needed to be effective educators. METHODS: This is a
      discussion paper based on a wide reading of the literature on the education of
      health professionals with a specific focus on roles and competences of educators.
      RESULTS AND DISCUSSION: Roles of educators of undergraduate dental students
      typically encompass four areas: teaching, research, administration and providing
      healthcare. Educators may not be involved in every role; they normally perform
      the roles relevant to their work contexts. Competences for dental educators based
      on the four main roles comprise 12 domains: educational theories and principles;
      modes of education; learner issues; educational materials and instructional
      design; assessment and feedback; curriculum matters; evaluation; educational
      research; educational management; quality assurance; patient care and healthcare
      system and professionalism. Not all competences are required by all educators
      although educators need to be competent in the areas related to their roles and
      duties. CONCLUSION: Understanding the roles and competences for educators of
      undergraduate dental students can help individual educators to improve their
      personal effectiveness and institutions to tailor staff development programmes
      appropriate to the needs of their staff. Faculty development contributes to
      sustained enhancement of undergraduate dental education.

PMID- 27864860
TI  - Evaluation of a loop-mediated isothermal amplification assay based on hrpZ gene
      for rapid detection and identification of Pseudomonas syringae pv. lachrymans in
      cucumber leaves.
AB  - AIMS: Cucumber angular leaf spot caused by Pseudomonas syringae pv. lachrymans
      (Psl) is an important and destructive disease worldwide, and no effective
      technique has been developed for the control of the pathogen. Detection of
      infection or latent in cucumber plants is critical to evaluate disease progress
      and strengthening management to avoid a serious epidemic in the fields. In this
      paper, we developed a rapid and sensitive method for detection of Psl using an
      isothermal method known as loop-mediated amplification (LAMP). METHODS AND
      RESULTS: A set of six primers was designed to amplify the gene coding for the
      hrpZ, and conditions for detection were optimized to complete in 60 min at 67
      degrees C, and the amplification were confirmed through gel electrophoresis or
      visually inspected using calcein stain. The specificity of LAMP primers set was
      widely validated on Psl and nontarget strains. In sensitivity testing, LAMP
      allowed detection as low as 104  CFU per ml bacterial cells without DNA
      extraction. The novel method was also applied for detecting Psl in infected
      cucumber leaves, and even the early onset of disease can be detected by the
      assay. CONCLUSIONS: This study confirmed that the novel developed LAMP assay is
      an easy, rapid and sensitive method for the detection of Psl in infected leaves.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The method is suitable for direct detection
      of Psl without strain enrichment and complex DNA extraction from samples in the
      field, and hence it has the capability to be used for on-site disease diagnosis
      and field surveys.

PMID- 27864862
TI  - Heparin-induced multi-electrode aggregometry method for heparin-induced
      thrombocytopenia testing: communication from the SSC of the ISTH.

PMID- 27864863
TI  - Subretinal neovascularization as the only ocular sign of osteogenesis imperfecta:
      a case report.

PMID- 27864861
TI  - Fight or flight? - Flight increases immune gene expression but does not help to
      fight an infection.
AB  - Flight represents a key trait in most insects, being energetically extremely
      demanding, yet often necessary for foraging and reproduction. Additionally,
      dispersal via flight is especially important for species living in fragmented
      landscapes. Even though, based on life-history theory, a negative relationship
      may be expected between flight and immunity, a number of previous studies have
      indicated flight to induce an increased immune response. In this study, we
      assessed whether induced immunity (i.e. immune gene expression) in response to 15
      min forced flight treatment impacts individual survival of bacterial infection in
      the Glanville fritillary butterfly (Melitaea cinxia). We were able to confirm
      previous findings of flight-induced immune gene expression, but still observed
      substantially stronger effects on both gene expression levels and life span due
      to bacterial infection compared to flight treatment. Even though gene expression
      levels of some immunity-related genes were elevated due to flight, these
      individuals did not show increased survival of bacterial infection, indicating
      that flight-induced immune activation does not completely protect them from the
      negative effects of bacterial infection. Finally, an interaction between flight
      and immune treatment indicated a potential trade-off: flight treatment increased
      immune gene expression in naive individuals only, whereas in infected individuals
      no increase in immune gene expression was induced by flight. Our results suggest
      that the up-regulation of immune genes upon flight is based on a general stress
      response rather than reflecting an adaptive response to cope with potential
      infections during flight or in new habitats.

PMID- 27864865
TI  - Introduction to symposium: 'New genetics with impact on treatment of endocrine
      tumour disease'.

PMID- 27864864
TI  - Genetics of adrenocortical tumours.
AB  - The recently available genomic sequencing techniques have led to breakthroughs in
      understanding of the underlying genetic mechanisms in adrenocortical tumours.
      Disease-causing mutations have been described for aldosterone-producing adenomas,
      cortisol-producing adenomas and adrenocortical carcinomas. Further, knowledge
      gained from transcriptome analyses and methylation arrays has provided new
      insights into the development of these tumours. Elucidation of the genomic
      landscape of adrenocortical tumours and improved techniques may in the future be
      useful for early diagnosis through the detection of mutated DNA in the
      circulation. Moreover, compounds that bind specifically to altered proteins may
      be used as screening targets or therapeutic agents. Regulation of cortisol
      release by interaction with an altered subunit in adenylate cyclase may be more
      complex, but may provide a new option for regulating steroid release. Information
      about derangements in adrenocortical carcinoma is already helpful for determining
      patient prognosis. With further knowledge, we may be able to identify novel
      biomarkers that effectively and noninvasively help in differentiating between
      benign and malignant disease. It is clear that the next few years will provide
      much novel information that hopefully will aid in the treatment of patients with
      adrenocortical tumours.

PMID- 27864867
TI  - Potential beneficial effect of low-dose danazol in combination with renin
      angiotensin system inhibitors in diabetic macular oedema.

PMID- 27864868
TI  - Repigmentation in vitiligo: position paper of the Vitiligo Global Issues
      Consensus Conference.
AB  - The Vitiligo Global Issues Consensus Conference (VGICC), through an international
      e-Delphi consensus, concluded that 'repigmentation' and 'maintenance of gained
      repigmentation' are essential core outcome measures in future vitiligo trials.
      This VGICC position paper addresses these core topics in two sections and
      includes an atlas depicting vitiligo repigmentation patterns and color match. The
      first section delineates mechanisms and characteristics of vitiligo
      repigmentation, and the second section summarizes the outcomes of international
      meeting discussions and two e-surveys on vitiligo repigmentation, which had been
      carried out over 3 yr. Treatment is defined as successful if repigmentation
      exceeds 80% and at least 80% of the gained repigmentation is maintained for over
      6 months. No agreement was found on the best outcome measure for assessing target
      or global repigmentation, therefore highlighting the limitations of e-surveys in
      addressing clinical measurements. Until there is a clear consensus, existing
      tools should be selected according to the specific needs of each study. A
      workshop will be conducted to address the remaining issues so as to achieve a
      consensus.

PMID- 27864870
TI  - Hereditary hemorrhagic telangiectasia: to transplant or not to transplant?
AB  - This report comments the case reported by Muller et al. which describes a
      combination of at least two different indications for orthotopic liver transplant
      (OLT) in a same patient: hepatocarcinoma and HHT complicated with severe liver
      involvement and high output cardiac failure. This case report highlighted that
      the clear time for OLT in HHT can be difficult to determine. In HHT, if intensive
      medical approach is not efficient, OLT, has to be considered. In the case of
      Muller et al., the patient was correctly listed for OLT for a single
      hepatocellular carcinoma, however, he did not receive a sufficient priority so as
      to avoid worsening of liver vascular malformations complications. Bevacizumab may
      be a therapeutic option in the treatment of complicated liver VMs in HHT,
      However, the recurrence of symptoms after withdrawal of the drug make it
      unsuitable as a replacement for OLT in the cure of complicated liver VMs in HHT.
      In the case reported by Muller et al. the right "OLT window" after bevacizumab
      was lost. The right time for OLT in severe complicated liver VMs in HHT does
      exist but, as this case illustrates, it can be very difficult to determine. As
      OLT is a radical cure for liver VMs, with excellent outcomes, it should be the
      therapeutic choice in patients under the age of 65 years. Bevacizumab may be an
      interesting option, either for patients over the age of 65 years, or those who
      are poor candidates for surgery; if these latter respond to bevacizumab they
      should be re- evaluated for OLT (with a "fast- track") as the prognosis of severe
      complicated liver VMs is very poor.

PMID- 27864871
TI  - Hereditary haemorrhagic telangiectasia: to transplant or not to transplant?
AB  - The Association of hereditary hemorrhagic telangiectasia (HHT) and type I
      hereditary angioedema is a very rare condition in medicine. The case reported by
      Muller et al., describes the coexistence of the two diseases and emphasizes the
      need for listing HHT patients for liver transplantation in case indications
      occurs, such as the presence of HCC, abnormally increased cardiac output, and
      gastrointestinal bleeding as reported for this case. The case described by
      Mueller et al. is anecdotal for the usefulness of liver transplantation in HHT
      patients and shows that liver transplantation may be the best supportive care
      and, sometimes, the unique and final therapeutic option for these patients.

PMID- 27864872
TI  - Management of hepatitis B-related cirrhosis in the era of effective antiviral
      therapy.

PMID- 27864869
TI  - Anthoxanthin Polyphenols Attenuate Abeta Oligomer-induced Neuronal Responses
      Associated with Alzheimer's Disease.
AB  - AIMS: Epidemiological evidence implicates polyphenols as potential natural
      therapeutics for Alzheimer's disease (AD). To investigate this prospect, five
      anthoxanthin polyphenols were characterized for their ability to reduce amyloid
      beta (Abeta) oligomer-induced neuronal responses by two mechanisms of action,
      modulation of oligomerization and antioxidant activity, as well as the synergy
      between these two mechanisms. METHODS: Anthoxanthin oligomerization modulation
      and antioxidant capabilities were evaluated and correlated with anthoxanthin
      attenuation of oligomer-induced intracellular reactive oxygen species (ROS) and
      caspase activation using human neuroblastoma cell treatments designed to isolate
      these mechanisms of action and to achieve dual-action. RESULTS: While modulation
      of oligomerization resulted in only minor reductions to neuronal responses,
      anthoxanthin antioxidant action significantly attenuated oligomer-induced
      intracellular ROS and caspase activation. Kaempferol uniquely exhibited synergism
      when the two mechanisms functioned in concert, leading to a pronounced reduction
      in both ROS and caspase activation. CONCLUSIONS: Together, these findings
      identify the dominant mechanism by which these anthoxanthins attenuate Abeta
      oligomer-induced neuronal responses, elucidate their prospective synergy, and
      demonstrate the potential of anthoxanthin polyphenols as natural AD therapeutics.

PMID- 27864873
TI  - Hereditary haemorrhagic telangiectasia: to transplant or not to transplant - is
      there a right time for liver transplantation?
AB  - BACKGROUND & AIMS: Hereditary haemorrhagic telangiectasia is characterized by
      arterio-venous malformations (AVM). It frequently involves the liver without
      clinical symptoms, but may lead to biliary ischaemia, portal hypertension, or
      fatal high-output heart failure. The indication of liver transplantation is
      controversial. METHODS: Herein, we report the case of a 65-year-old female
      patient with a 'double Osler syndrome' consisting of hereditary haemorrhagic
      telangiectasia (HHT) and type I hereditary angioedema diagnosed at the age of 25
      and 22 years respectively. RESULTS: Hereditary angioedema was treated with
      danazol for several decades until multiple hypoechogenic liver masses were
      detected. Albeit danazol treatment was replaced by C1 esterase inhibitor
      infusions, hepatocellular carcinoma was diagnosed at the age of 64 and the
      patient was listed for liver transplantation. HHT was marked by recurrent
      epistaxis until the age of 63 when severe intestinal bleeding occurred. At the
      age of 65, severe dyspnoea (NYHA class IV) developed and rapidly progressive high
      output cardiac failure was diagnosed. Despite argon plasma coagulation to control
      bleeding from intestinal angiodysplasia, and treatment with bevacizumab to
      inhibit angiogenesis, the patient died from severe gastrointestinal bleeding
      associated with cardiogenic shock at the age of 66 before being transplanted.
      CONCLUSION: The indication to list this patient for liver transplantation was
      debated several times before the diagnosis of hepatocellular carcinoma because of
      good general condition and low MELD score. Precise guidelines for screening and
      management of patients with hepatic HHT need to be better defined.

PMID- 27864874
TI  - Prognostic biomarkers and surrogate end points in PSC.

PMID- 27864875
TI  - Response to Ablation and resection for hepatocellular carcinoma within the Milan
      criteria and high alpha-fetoprotein levels.

PMID- 27864877
TI  - The role of retinopathy distribution and other lesion types for the definition of
      examination intervals during screening for diabetic retinopathy.
AB  - PURPOSE: It has previously been shown that the intervals between screening
      examinations for diabetic retinopathy can be optimized by including individual
      risk factors for the development of the disease in the risk assessment. However,
      in some cases, the risk model calculating the screening interval may recommend a
      different interval than an experienced clinician. The purpose of this study was
      to evaluate the influence of factors unrelated to diabetic retinopathy and the
      distribution of lesions for discrepancies between decisions made by the clinician
      and the risk model. METHODS: Therefore, fundus photographs from 90 screening
      examinations where the recommendations of the clinician and a risk model had been
      discrepant were evaluated. Forty features were defined to describe the type and
      location of the lesions, and classification and ranking techniques were used to
      assess whether the features could predict the discrepancy between the grader and
      the risk model. RESULTS: Suspicion of tumours, retinal degeneration and vascular
      diseases other than diabetic retinopathy could explain why the clinician
      recommended shorter examination intervals than the model. Additionally, the
      regional distribution of microaneurysms/dot haemorrhages was important for
      defining a photograph as belonging to the group where both the clinician and the
      risk model had recommended a short screening interval as opposed to the other
      decision alternatives. CONCLUSIONS: Features unrelated to diabetic retinopathy
      and the regional distribution of retinal lesions may affect the recommendation of
      the examination interval during screening for diabetic retinopathy. The
      development of automated computerized algorithms for extracting information about
      the type and location of retinal lesions could be expected to further optimize
      examination intervals during screening for diabetic retinopathy.

PMID- 27864878
TI  - Toric intraocular lens implantation in children with developmental cataract and
      preexisting corneal astigmatism.

PMID- 27864879
TI  - Highly Fluorescent Non-Conventional Boron-Difluoride-Based pi Organogel with
      Gelation-Assisted Piezochromism.
AB  - Triphenylamine-functionalized boron 2-(2'-pyridyl)imidazole complex bearing no
      alkyl chains or H-bond unit was found to be able to gelate a series of solvents,
      and the balanced intermolecular pi-pi interactions play an important role in its
      supramolecular self-assembly. The gelator molecule is piezochromic, and the dried
      gel responded to pressure more sensitively than regular crystalline powder.

PMID- 27864876
TI  - Kinase gene fusions in defined subsets of melanoma.
AB  - Genomic rearrangements resulting in activating kinase fusions have been
      increasingly described in a number of cancers including malignant melanoma, but
      their frequency in specific melanoma subtypes has not been reported. We used
      break-apart fluorescence in situ hybridization (FISH) to identify genomic
      rearrangements in tissues from 59 patients with various types of malignant
      melanoma including acral lentiginous, mucosal, superficial spreading, and
      nodular. We identified four genomic rearrangements involving the genes BRAF, RET,
      and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or
      sequencing and one was found to be an ARMC10-BRAF fusion that has not been
      previously reported in melanoma. These fusions occurred in different subtypes of
      melanoma but all in tumors lacking known driver mutations. Our data suggest gene
      fusions are more common than previously thought and should be further explored
      particularly in melanomas lacking known driver mutations.

PMID- 27864880
TI  - Preoperative and postoperative measurements of retinal vessel oxygen saturation
      in patients with different grades of cataracts.
AB  - PURPOSE: To assess the retinal vessel blood oxygen saturation preoperatively and
      postoperatively in patients with different grades of cataracts. METHODS: This
      study included 40 eyes from 40 patients with senile cataracts ranging from grade
      1 to 3. All 40 eyes received standard phacoemulsification and intraocular lens
      implantation. The mean retinal arterial and venular oxygen saturation (SO2 )
      levels were measured using the Oxymap system prior to, immediately after and 3
      months after cataract surgery. The arterial-venular difference (AVD) was
      calculated as the difference between the arterial and venular saturations. Linear
      regression analysis was performed to identify the relationship between the lens
      density grades and changes in the measured retina vessel SO2 . RESULTS: The mean
      age of the subjects was 64.1 +/- 7.8 years, and 14 (35%) were male. The mean SO2
      level increased in the retinal arterioles from 90.5 +/- 7.8% to 95.0 +/- 6.7%
      immediately postoperatively and to 98.3 +/- 5.3% at 3 months after surgery (p <
      0.001). The mean venular saturation levels were 43.4 +/- 9.7%, 58.0 +/- 8.5% and
      61.9 +/- 6.5% at baseline, immediately after and at 3 months postoperatively,
      respectively, with a statistically significant increase after surgery (p <
      0.001). The mean AVD significantly decreased from 47.1 +/- 8.9% before surgery to
      37.1 +/- 7.3% immediately after and 36.4 +/- 6.4% 3 months after surgery (p <
      0.02). A linear regression model indicated that denser lens opacity was
      significantly associated with a larger amplitude of the venular SO2 level and the
      AVD after cataract surgery: change of venous SO2  = 5.934-0.191 * Age + 13.534 *
      Lens Grade (age: p = 0.586; lens grade: p < 0.001); change in AVD = -7.438-0.037
      * Age + 7.744 * Lens Grade (age: p = 0.917; lens grade: p = 0.031). CONCLUSIONS:
      Retinal arterial and venular oxygen saturation levels are significantly increased
      after cataract surgery, and increase rates vary with the preoperative grading of
      lens density.

PMID- 27864881
TI  - Visual system manifestations of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an increasingly common disease with massive personal
      and economic costs. While it has long been known that AD impacts the visual
      system, there has recently been an increased focus on understanding both
      pathophysiological mechanisms that may be shared between the eye and brain and
      how related biomarkers could be useful for AD diagnosis. Here, were review
      pertinent cellular and molecular mechanisms of AD pathophysiology, the presence
      of AD pathology in the visual system, associated functional changes, and
      potential development of diagnostic tools based on the visual system.
      Additionally, we discuss links between AD and visual disorders, including
      possible pathophysiological mechanisms and their relevance for improving our
      understanding of AD.

PMID- 27864882
TI  - Diversification of the kinetic properties of yeast NADP-glutamate-dehydrogenase
      isozymes proceeds independently of their evolutionary origin.
AB  - In the yeast Saccharomyces cerevisiae, the ScGDH1 and ScGDH3 encoded glutamate
      dehydrogenases (NADP-GDHs) catalyze the synthesis of glutamate from ammonium and
      alpha-ketoglutarate (alpha-KG). Previous kinetic characterization showed that
      these enzymes displayed different allosteric properties and respectively high or
      low rate of alpha-KG utilization. Accordingly, the coordinated action of ScGdh1
      and ScGdh3, regulated balanced alpha-KG utilization for glutamate biosynthesis
      under either fermentative or respiratory conditions, safeguarding energy
      provision. Here, we have addressed the question of whether there is a correlation
      between the regulation and kinetic properties of the NADP-GDH isozymes present in
      S. cerevisiae (ScGdh1 and ScGdh3), Kluyveromyces lactis (KlGdh1), and Lachancea
      kluyveri (LkGdh1) and their evolutionary history. Our results show that the
      kinetic properties of K. lactis and L. kluyveri single NADP-GDHs are respectively
      similar to either ScGDH3 or ScGDH1, which arose from the whole genome duplication
      event of the S. cerevisiae lineage, although, KlGDH1 and LkGDH1 originated from a
      GDH clade, through an ancient interspecies hybridization event that preceded the
      divergence between the Saccharomyces clade and the one containing the genera
      Kluyveromyces, Lachancea, and Eremothecium. Thus, the kinetic properties which
      determine the NADP-GDHs capacity to utilize alpha-KG and synthesize glutamate do
      not correlate with their evolutionary origin.

PMID- 27864883
TI  - Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain.
AB  - The asexual freshwater planarian is a constitutive adult, whose central nervous
      system (CNS) is in a state of constant homeostatic neurogenesis. However, very
      little is known about the extrinsic signals that act on planarian stem cells to
      modulate rates of neurogenesis. We have identified two planarian homeobox
      transcription factors, Smed-nkx2.1 and Smed-arx, which are required for the
      maintenance of cholinergic, GABAergic, and octopaminergic neurons in the
      planarian CNS. These very same neurons also produce the planarian hedgehog ligand
      (Smed-hh), which appears to communicate with brain-adjacent stem cells to promote
      normal levels of neurogenesis. Planarian stem cells nearby the brain express core
      hh signal transduction genes, and consistent hh signaling levels are required to
      maintain normal production of neural progenitor cells and new mature cholinergic
      neurons, revealing an important mitogenic role for the planarian hh signaling
      molecule in the adult CNS.

PMID- 27864885
TI  - Phylogenetic and Functional Classification of the Photolyase/Cryptochrome Family.
AB  - The photolyase/cryptochrome (PHR/CRY) family is a large group of proteins with
      similar structure but very diverge functions such as DNA repair, circadian clock
      resetting and regulation of transcription. As a result of advances in the
      biochemistry of the CRY/PHR family and identification of new members, several
      adjustments have been made to the classification of this protein family. For
      example, a new class of PHRs, Class III, has been proposed. Furthermore, CRYs
      have been suggested to function as photosensory proteins in the primordial eye of
      sponge larvae. Additionally, a magnetosensory function has been attributed to
      certain CRYs. Recent advances in the field enabled us to propose a comprehensive
      classification scheme and nomenclatural system for this family. This review
      focuses on the computational and biochemical classifications of the PHR/CRY
      family. Several examples show that computational analysis can give a hinge about
      the function of newly discovered members before performing any biochemical study.

PMID- 27864884
TI  - Mfd Protein and Transcription-Repair Coupling in Escherichia coli.
AB  - In 1989, transcription-repair coupling (TRC) was first described in Escherichia
      coli, as the transcription-dependent, preferential nucleotide excision repair
      (NER) of UV photoproducts located in the template DNA strand. This finding led to
      pioneering biochemical studies of TRC in the laboratory of Professor Aziz Sancar,
      where, at the time, major contributions were being made toward understanding the
      roles of the UvrA, UvrB and UvrC proteins in NER. When the repair studies were
      extended to TRC, template but not coding strand lesions were found to block RNA
      polymerase (RNAP) in vitro, and unexpectedly, the blocked RNAP inhibited NER. A
      transcription-repair coupling factor, also called Mfd protein, was found to
      remove the blocked RNAP, deliver the repair enzyme to the lesion and thereby
      mediate more rapid repair of the transcription-blocking lesion compared with
      lesions elsewhere. Structural and functional analyses of Mfd protein revealed
      helicase motifs responsible for ATP hydrolysis and DNA binding, and regions that
      interact with RNAP and UvrA. These and additional studies provided a basis upon
      which other investigators, in following decades, have characterized fascinating
      and unexpected structural and mechanistic features of Mfd, revealed the possible
      existence of additional pathways of TRC and discovered additional roles of Mfd in
      the cell.

PMID- 27864887
TI  - Ethical use of animal models in musculoskeletal research.
AB  - The use of animals in research is under increasing scrutiny from the general
      public, funding agencies, and regulatory authorities. Our ability to continue to
      perform in-vivo studies in laboratory animals will be critically determined by
      how researchers respond to this new reality. This Perspectives article summarizes
      recent and ongoing initiatives within ORS and allied organizations to ensure that
      musculoskeletal research is performed to the highest ethical standards. It goes
      on to present an overview of the practical application of the 3Rs (reduction,
      refinement, and replacement) into experimental design and execution, and
      discusses recent guidance with regard to improvements in the way in which animal
      data are reported in publications. The overarching goal of this review is to
      challenge the status quo, to highlight the absolute interdependence between
      animal welfare and rigorous science, and to provide practical recommendations and
      resources to allow clinicians and scientists to optimize the ways in which they
      undertake preclinical studies involving animals. (c) 2016 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:740-751, 2017.

PMID- 27864886
TI  - Perceptions of risks for diabetes-related complications in Type 2 diabetes
      populations: a systematic review.
AB  - AIM: In Type 2 diabetes, there is no clear understanding of how people perceive
      their risk of experiencing diabetes-related complications. To address this issue,
      we undertook an evidence-based synthesis of how people with Type 2 diabetes
      perceive their risk of complications. METHODS: We performed a systematic search
      of nine electronic databases for peer-reviewed articles published on or before 1
      March 2016. Data from 18 studies reporting lay perceptions of risks for
      complications in Type 2 diabetes populations were included. Publication year
      ranged between 2002 and 2014. RESULTS: Methods used to assess risk perceptions
      were heterogeneous, ranging from questionnaires measuring the accuracy of
      perceived risks to semi-structured and focus group interviews. We found evidence
      of low risk awareness in most dimensions of risk perceptions measured and the
      existence of optimistic bias. CONCLUSIONS: Perceptions were generally biased and
      varied according to the dimension of risk measured, the subpopulation concerned
      and the type of complications considered. Future work is needed to identify the
      best practical ways of correcting for biased risk perceptions so as to encourage
      self-care behaviours and treatment adherence.

PMID- 27864888
TI  - EBV infection is prevalent in the adenoid and palatine tonsils in adults.
AB  - Epstein-Barr virus (EBV) is associated with the pathogenesis of several diseases
      in both adults and children. However, there have been no reports on the
      prevalence and amount of EBV in the adenoids of adults; thus, it is important to
      investigate these in the adenoids and tonsils of adults and children. In this
      study, 67 patients who underwent tonsillectomy or adenotonsillectomy were
      included and divided into two groups: adults aged >= 16 years (n = 35) and
      children aged <16 years (n = 32). Patients' adenoid and tonsil tissues were
      analyzed using quantitative polymerase chain reaction for EBV DNA. EBV was
      detected in 26 (74%) adenoids and 25 (71%) tonsils among the adult group and was
      detected 21 (66%) adenoids and 20 (63%) tonsils in the child group. There was no
      significant difference in EBV DNA prevalence between the adenoids and tonsils for
      each group. However, there was a significant correlation between EBV DNA load in
      the adenoids and tonsils of the same individual in both groups (r = 0.579, P <
      0.01, adult group; r = 0.919, P < 0.01, child group). In conclusion, EBV
      infection is prevalent in the adenoids and tonsils in adults and children. These
      results indicate that EBV continuously reside in the nasopharyngeal region after
      primal infection and may develop several diseases.

PMID- 27864889
TI  - Goal-Directed Treatment for Osteoporosis: A Progress Report From the ASBMR-NOF
      Working Group on Goal-Directed Treatment for Osteoporosis.
AB  - The American Society for Bone and Mineral Research and the United States National
      Osteoporosis Foundation (NOF) formed a working group to develop principles of
      goal-directed treatment and identify gaps that need to be filled to implement
      this approach. With goal-directed treatment, a treatment goal would first be
      established and choice of treatment determined by the probability of achieving
      that goal. Goals of treatment would be freedom from fracture, a T-score > -2.5,
      which is above the NOF threshold for initiating treatment, or achievement of an
      estimated risk level below the threshold for initiating treatment. Progress
      toward reaching the patient's goal would be periodically and systematically
      assessed by estimating the patient's compliance with treatment, reviewing
      fracture history, repeating vertebral imaging when indicated, and repeating
      measurement of bone mineral density (BMD). Using these data, a decision would be
      made to stop, continue, or change therapy. Some of these approaches can now be
      applied to clinical practice. However, the application of goal-directed treatment
      cannot be fully achieved until medications are available that provide greater
      increases in BMD and greater reduction in fracture risk than those that are
      currently approved; only then can patients with very high fracture risk and very
      low BMD achieve such goals. Furthermore, assessing future fracture risk in
      patients on treatment requires a new assessment tool that accurately captures the
      change in fracture risk associated with treatment and should also be sensitive to
      the importance of recent fractures as predictors of imminent fracture risk.
      Lastly, evidence is needed to confirm that selecting and switching treatments to
      achieve goals reduces fracture risk more effectively than current standard care.
      (c) 2016 American Society for Bone and Mineral Research.

PMID- 27864890
TI  - Anti-EGFR monoclonal antibodies enhance sensitivity to DNA-damaging agents in
      BRCA1-mutated and PTEN-wild-type triple-negative breast cancer cells.
AB  - Increased epidermal growth factor receptor (EGFR) expression in triple-negative
      breast cancer (TNBC) is recognized as a promising therapeutic target,
      specifically through the use of selective EGFR inhibitors combined with
      chemotherapies. TNBC is characterized by genetic instability that leads to
      increased sensitivity to cytotoxic agents. We analyzed the effect of anti-EGFR
      monoclonal antibodies (mAbs; cetuximab and panitumumab) in combination with
      chemotherapeutic agents (docetaxel, cisplatin, and epirubicin) on EGFR-expressing
      TNBC cell lines that have different mutation statuses for one oncogene (KRAS) and
      two tumor suppressor genes (PTEN and BRCA1). Both mAbs failed to improve the
      cytotoxic effect of chemotherapies in the KRAS mutant cell line (MDA-MB-231) and
      PTEN-null cell lines (HCC-1937 and MDA-MB-468). In contrast, mAbs combined with
      DNA-damaging agents (cisplatin or epirubicin) had a synergistic effect in the
      BRCA1-mutant cell line SUM-1315 (wild-type KRAS and PTEN). The reintroduction of
      wild-type BRCA1 into SUM-1315 cells abolished this synergism. The improved effect
      of combination therapy was associated with cell cycle arrest at G1 phase and
      inhibition of the phosphorylation of EGFR and ERK1/2 proteins. These results
      suggest that patients with BRCA1-associated TNBC without genetic alterations in
      the PTEN and KRAS genes may have improved therapeutic responses to anti-EGFR mAbs
      combined with DNA-damaging agents. (c) 2017 Wiley Periodicals, Inc.

PMID- 27864891
TI  - 3D MRI Quantification of Femoral Head Deformity in Legg-Calve-Perthes Disease.
AB  - The purpose of this study was to quantify femoral head deformity in patients with
      Legg-Calve-Perthes disease (LCPD) using a novel three dimensional (3D) magnetic
      resonance imaging (MRI) reconstruction and volume based analysis. Bilateral
      femoral heads of 17 patients (mean age 9.9 +/- 2.0 years; 12 boys, 5 girls) with
      LCPD were scanned 1-2 times (n = 33 LCPD heads, 20 normal heads) using a 1.5T MRI
      scanner. Fourteen patients had unilateral and three had bilateral LCPD with five
      hips in the Waldenstrom initial stage, 9 in the fragmentation stage, 14 in the
      reossification stage, and 5 in the healed stage. 3D digital reconstructions of
      femoral heads were created using MIMICS software. Deformity was quantified using
      a 3D volume ratio method based on reference hemisphere volume as well as two
      surface geometry methods. Intra-observer analysis showed that 97% of the LCPD
      femoral heads were within 10% of the original value and test shapes had 99.6%
      accuracy. For normal femoral heads, the volume ratios of all except one were
      between 95 and 98% (n = 20) of a perfect hemisphere volume. For femoral heads
      affected with LCPD, the volume ratios ranged from 43% to 96% of a perfect
      hemisphere (n = 33). The volume ratio method and the two surface geometry
      comparison methods had high correlation (r = 0.89 and 0.96). In summary, the 3D
      MRI volume ratio method allowed accurate quantification and demonstrated small
      changes (<10%) of the femoral head deformity in LCPD. This method may serve as a
      useful tool to evaluate the effects of treatment on femoral head shape. (c) 2016
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      35:2051-2058, 2017.

PMID- 27864892
TI  - Introgression of mtDNA in Urosaurus lizards: historical and ecological processes.
AB  - Introgression of mtDNA appears common in animals, but the implications of
      acquiring a novel mitochondrial genome are not well known. This study
      investigates mito-genome introgression between the lizard species Urosaurus
      graciosus, a thermal specialist, and U. ornatus, a species that occupies a wider
      range of thermal environments. As ectotherms, their metabolic rate is strongly
      influenced by the thermal environment; with mitochondria being linked to
      metabolic rates, overall energy budgets could be impacted by introgression. I use
      mitochondrial gene trees, inferred from Bayesian analyses of Cyt-B and ND1 gene
      sequences, along with morphology and microsatellites from nineteen populations of
      these two species to address if the direction and location of mito-nuclear
      discordance match predictions of introgression resulting from past population
      expansions. MtDNA is expected to move from resident species into expanding or
      invading species. Second, does having a heterospecific form of mitochondria
      impact body size, a trait strongly associated with fitness? Multiple independent
      introgression events of historic origin were detected. All introgression was
      unidirectional with U. ornatus-type mtDNA found in U. graciosus parental type
      individuals. This result was consistent with population expansions detected in U.
      graciosus but not U. ornatus. Females with heterospecific mtDNA were
      significantly smaller than homospecific forms, and heterospecific males had a
      different relationship of body mass to body length than those with homospecific
      mtDNA. These changes indicate a potential selective disadvantage for individuals
      with heterospecific mitochondria and are consistent with the theoretical
      expectation that deleterious alleles are more likely to persist in expanding
      populations.

PMID- 27864893
TI  - High alcohol intake in deceased donors has no effect on pancreas graft survival:
      a registry analysis.
AB  - Outcomes of pancreas transplantation from donors with high alcohol consumption
      are poorly described. The UK Transplant Registry was used to determine whether
      donor alcohol intake influenced pancreas survival in simultaneous pancreas-kidney
      (SPK) transplants performed between 2006 and 2012 (n = 770). Recipients were
      stratified by donor alcohol intake: group I (n = 122)-high recent alcohol intake
      (>21 or >14 units of alcohol/week in males or females, respectively) or previous
      alcohol abuse and group II (n = 648)-low/unknown current intake and no previous
      alcohol abuse. Median current alcohol intake was higher in group I than group II:
      36.3 vs. 10 units/week; P < 0.001. One- and five-year pancreas graft survivals
      were 88.5% and 73.6% in group I, and 87% and 74.9% in group II. There was no
      difference in unadjusted graft survival between groups I and II (P = 0.76), and
      no difference between group II and a subgroup of group I with a donor history of
      alcohol abuse and high current intake (P = 0.26), or from donors with current
      alcohol consumption of >50 units/week (P = 0.41). Pancreas donors with past
      alcohol abuse or current high intake are common, and graft outcomes appear to be
      acceptable. This analysis suggests that high donor alcohol intake, by itself,
      should not exclude consideration of pancreas transplantation.

PMID- 27864894
TI  - Maternal dietary intake in pregnancy and lactation and allergic disease outcomes
      in offspring.
AB  - As the prevalence of allergic disease dramatically rises worldwide, prevention
      strategies are increasingly being considered. Given the potential modulatory
      effect of nutritional factors on disease, altering maternal diet during pregnancy
      and/or lactation has been considered in preventing allergic disease in offspring.
      Although there are a number of observational studies that have examined possible
      associations between maternal diet and allergic outcomes in offspring,
      interventional trials are limited. Furthermore, there is a paucity of studies
      that have prospectively studied maternal dietary intake as well as measuring
      maternal and infant biologic samples (blood, urine, breast milk) and their
      relation to allergic outcomes in infants. There is also a particular need to
      define terminology such as 'fruit and vegetables intake', 'healthy diet', and
      'diet diversity' in order to make studies comparable. In this review, we discuss
      current evidence of maternal dietary factors during pregnancy and/or lactation
      that may play a role in the offspring developing allergic disease, including
      factors such as overall dietary intake patterns, specific whole food consumption
      (fish, fruit and vegetables, and common allergic foods), and individual
      immunomodulatory nutrient intakes. Additionally, we discuss the limitations of
      previous studies and propose improvements to study design for future
      investigation.

PMID- 27864896
TI  - Family Medical History.

PMID- 27864895
TI  - The postreperfusion syndrome is associated with acute kidney injury following
      donation after brain death liver transplantation.
AB  - Acute kidney injury (AKI) is frequently observed after donation after brain death
      (DBD) liver transplantation (LT) and associated with impaired recipient survival
      and chronic kidney disease. Hepatic ischemia/reperfusion injury (IRI) is
      suggested to be an important factor in this process. The postreperfusion syndrome
      (PRS) is the first manifestation of severe hepatic IRI directly after
      reperfusion. We performed a retrospective study on the relation between hepatic
      IRI and PRS and their impact on AKI in 155 DBD LT recipients. Severity of hepatic
      IRI was measured by peak postoperative AST levels and PRS was defined as >30%
      decrease in MAP >=1 min within 5 min after reperfusion. AKI was observed in 39%
      of the recipients. AKI was significantly more observed in recipients with PRS
      (53% vs. 32%; P = 0.013). Median peak AST level was higher in recipients with PRS
      (1388 vs. 771 U/l; P < 0.001). Decrease in MAP after reperfusion correlated well
      with both severity of AKI (P = 0.012) and hepatic IRI (P < 0.001). Multiple
      logistic regression identified PRS as an independent factor for postoperative AKI
      (OR 2.28; 95% CI 1.06-4.99; P = 0.035). In conclusion, PRS reflects severe
      hepatic IRI and predicts AKI after DBD LT. PRS immediately after reperfusion is
      an early warning sign and creates opportunities to preserve postoperative renal
      function.

PMID- 27864897
TI  - Tolerogenic dendritic cell therapy in organ transplantation.
AB  - Although the occurrence of acute rejection was significantly reduced and the
      allograft survival at 1 year was massively improved by the development of
      pharmacological immunosuppressive drugs, little progress has been made regarding
      long-term graft survival. Cell therapy appears to be an innovative and promising
      strategy to minimize the use of immunosuppression in transplantation and
      consequently increases long-term graft survival. The strength of cell therapy is
      that it will induce graft-specific tolerance and not a general immunosuppression
      of the patients. Several candidates, such as tolerogenic dendritic cells, have
      been gaining interest as an efficient means of promoting antigen-specific
      tolerance over recent years. Studies performed in rodent models have demonstrated
      the feasibility and efficacy of tolerogenic dendritic cells for the induction of
      tolerance in transplantation. In parallel, protocols to generate human
      tolerogenic dendritic cells in vitro have been defined, and some phase I clinical
      trials in autoimmune diseases have been recently performed to evaluate the safety
      of tolerogenic dendritic cell therapy. In this review, we will focus on the
      potential therapeutic interest of these cells in transplantation as well as their
      generation and characterization in humans. Finally, we will describe our current
      clinical trial using autologous tolerogenic dendritic cells in transplantation.

PMID- 27864898
TI  - Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1
      in vitro.
AB  - BACKGROUND: Equine herpesvirus-associated myeloencephalopathy is the result of
      endothelial cell infection of the spinal cord vasculature with equine herpesvirus
      1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires
      contact between infected peripheral blood mononuclear and endothelial cells.
      Inflammation generated during viraemia likely upregulates adhesion molecule
      expression on both cell types increasing contact and facilitating endothelial
      cell infection. OBJECTIVES: Evaluating the role of anti-inflammatory drugs in
      decreasing endothelial cell infection with EHV-1. STUDY DESIGN: In vitro assay,
      crossover design, multiple drug testing. METHODS: In vitro modified infectious
      centre assay using immortalised carotid artery endothelial cells or primary brain
      endothelial cells with plaque counts per well as outcome. Cells were either anti
      inflammatory drug treated or left untreated. RESULTS: Significant reduction of
      plaque count when cells were treated compared with untreated cells. No dose
      dependent effect when drug concentrations were increased to 10* dose. Treatment
      of both peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) is
      required for significant plaque count reduction. MAIN LIMITATIONS: In vitro
      study. CONCLUSIONS: Anti-inflammatory drugs decrease infection of endothelial
      cells likely by reducing contact between EHV-1 infected PBMC and endothelial
      cells in vitro. The role of adhesion molecules in this process needs further
      investigation. In vitro results suggest anti-inflammatory drug therapy during EHV
      1 infection and viraemia in horses could be clinically relevant.

PMID- 27864899
TI  - N-Glycosylation at Asn 402 Stabilizes N-Cadherin and Promotes Cell-Cell Adhesion
      of Glioma Cells.
AB  - Cadherin is crucial for cell-cell adhesion and N-glycosylation of N-cadherin has
      been implicated in the process of mammary, renal, and ovarian carcinogenesis.
      However, whether N-glycosylation of N-cadherin plays a role in glioma remains
      unknown. Previous studies had indicated that N-glycosylation could occur at three
      asparagine residues of N-cadherin. By generating and over-expressing N
      glycosylation-deficient N-cadherin mutants in the human glioma cell lines SHG66
      and U87, we found that mutation of N402 but not of the other potentially N
      glycosylated residues destabilized N-cadherin and led to its ubiquitylation and
      subsequent proteasomal degradation. Furthermore, destabilized N-cadherin
      inhibited cadherin-mediated cell-cell adhesion and promoted cell migration. Our
      findings reveal that N-glycosylation controls N-cadherin stability and plays a
      role in glioma migration. J. Cell. Biochem. 118: 1423-1431, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27864901
TI  - Kidney temperature course during living organ procurement and transplantation.
AB  - Little is known about the actual kidney graft temperature during the 2nd warm
      ischemia time (WIT2). We aimed to determine the actual temperature course of the
      WIT2, with emphasis on the 15  degrees C metabolic threshold. Data of 152
      consecutive adult living donor kidney transplantations were collected. The mean
      WIT2 was 41.3 +/- 10.1 (SD) minutes with a temperature of 5.4  degrees C at
      baseline which gradually increased to 13.7, 17.4, and 20.2  degrees C after 10,
      20, and 30 min, respectively. The percentage of kidneys with a temperature of 15 
      degrees C or higher was 81.2% after 20 min and 97.5% after 30 min. Duration of
      surgery (95% CI: -0.017 to -0.002, P = 0.02), multiple veins (95% CI: 0.0003
      2.720, P = 0.05) and WIT2 (95% CI: 0.016-0.099, P = 0.006) were associated with a
      rapid temperature increase. No correlation could be determined between a rapid
      temperature rise and diminished graft function. This study showed a rapid
      increase in kidney temperature during WIT2, wherein the 15  degrees C threshold
      was reached within 20 min in more than 80% of the patients.

PMID- 27864902
TI  - Quantitative structure-activity relationship and molecular docking revealed a
      potency of anti-hepatitis C virus drugs against human corona viruses.
AB  - A number of human coronaviruses (HCoVs) were reported in the last and present
      centuries. Some outbreaks of which (eg, SARS and MERS CoVs) caused the mortality
      of hundreds of people worldwide. The problem of finding a potent drug against
      HCoV strains lies in the inability of finding a drug that stops the viral
      replication through inhibiting its important proteins. In spite of its limited
      efficacy and potential side effects, Ribavirin is extensively used as a first
      choice against HCoVs. Therefore, scientists reverted towards the investigation of
      different drugs that can more specifically target proteins. In this study, four
      anti-HCV drugs (one approved by FDA and others under clinical trials) are tested
      against HCoV polymerases. Quantitative Structure-Activity Relationship (QSAR) and
      molecular docking are both used to compare the performance of the selected
      nucleotide inhibitors to their parent nucleotides and Ribavirin. Both QSAR and
      molecular docking showed that IDX-184 is superior compared to Ribavirin against
      MERS CoV, a result that was also reported for HCV. MK-0608 showed a performance
      that is comparable to Ribavirin. We strongly suggest an in vitro study on the
      potency of these two drugs against MERS CoV.

PMID- 27864900
TI  - Recombination rate variation in mice from an isolated island.
AB  - Recombination rate is a heritable trait that varies among individuals. Despite
      the major impact of recombination rate on patterns of genetic diversity and the
      efficacy of selection, natural variation in this phenotype remains poorly
      characterized. We present a comparison of genetic maps, sampling 1212 meioses,
      from a unique population of wild house mice (Mus musculus domesticus) that
      recently colonized remote Gough Island. Crosses to a mainland reference strain
      (WSB/EiJ) reveal pervasive variation in recombination rate among Gough Island
      mice, including subchromosomal intervals spanning up to 28% of the genome. In
      spite of this high level of polymorphism, the genomewide recombination rate does
      not significantly vary. In general, we find that recombination rate varies more
      when measured in smaller genomic intervals. Using the current standard genetic
      map of the laboratory mouse to polarize intervals with divergent recombination
      rates, we infer that the majority of evolutionary change occurred in one of the
      two tested lines of Gough Island mice. Our results confirm that natural
      populations harbour a high level of recombination rate polymorphism and highlight
      the disparities in recombination rate evolution across genomic scales.

PMID- 27864903
TI  - Long-term monitoring of cardiorespiratory patterns in drug-resistant epilepsy.
AB  - OBJECTIVE: Sudden unexplained death in epilepsy (SUDEP) during inpatient
      electroencephalography (EEG) monitoring has been a rare but potentially
      preventable event, with associated cardiopulmonary markers. To date, no
      systematic evaluation of alarm settings for a continuous pulse oximeter (SpO2 )
      has been performed. In addition, evaluation of the interrelationship between the
      ictal and interictal states for cardiopulmonary measures has not been reported.
      METHODS: Patients with epilepsy were monitored using video-EEG, SpO2 , and
      electrocardiography (ECG). Alarm thresholds were tested systematically, balancing
      the number of false alarms with true seizure detections. Additional
      cardiopulmonary patterns were explored using automated ECG analysis software.
      RESULTS: One hundred ninety-three seizures (32 generalized) were evaluated from
      45 patients (7,104 h recorded). Alarm thresholds of 80-86% SpO2 detected 63-73%
      of all generalized convulsions and 20-28% of all focal seizures (81-94% of
      generalized and 25-36% of focal seizures when considering only evaluable data).
      These same thresholds resulted in 25-146 min between false alarms. The sequential
      probability of ictal SpO2 revealed a potential common seizure termination pathway
      of desaturation. A statistical model of corrected QT intervals (QTc), heart rate
      (HR), and SpO2 revealed close cardiopulmonary coupling ictally. Joint probability
      maps of QTc and SpO2 demonstrated that many patients had baseline dysfunction in
      either cardiac, pulmonary, or both domains, and that ictally there was
      dissociation-some patients exhibited further dysfunction in one or both domains.
      SIGNIFICANCE: Optimal selection of continuous pulse oximetry thresholds involves
      a tradeoff between seizure detection accuracy and false alarm frequency. Alarming
      at 86% for patients that tend to have fewer false alarms and at 80% for those who
      have more, would likely result in a reasonable tradeoff. The cardiopulmonary
      findings may lead to SUDEP biomarkers and early seizure termination therapies.

PMID- 27864904
TI  - An update on the current management of head and neck mucosal melanoma.
AB  - Primary mucosal melanomas of the head and neck are rare and aggressive tumours
      that arise in the nasal cavity, paranasal sinuses and more rarely in the oral
      cavity. The current treatment options include radical surgical resection with
      adjuvant external beam radiotherapy being offered in high-risk patients. Although
      the latter can improve regional control, it does not reduce overall survival.
      Elective neck dissection is recommended for nodular oral mucosal melanoma, but
      its role in the clinically node negative neck is controversial. Systemic
      therapies including the use of tyrosine kinase inhibitors for tumours with c-KIT
      mutations are suitable for patients with advanced loco-regional and/or metastatic
      disease, but current results are variable. Patients with head and neck mucosal
      melanoma have a poor prognosis due to the high incidence of metastatic disease.
      This review assesses the latest evidence in the diagnosis and management of
      primary oral and head and neck mucosal melanoma including details of systemic
      therapies.

PMID- 27864905
TI  - Polyacrylamide gel as a culture substrate improves in vitro oocyte growth from
      porcine early antral follicles.
AB  - A major difference between in vivo and in vitro follicle culture is the stiffness
      of the substrate in which the follicles grow. In this study, we examined the
      effect of polyacrylamide gel (PAG), as a culture substrate, on the development of
      porcine oocytes derived from early antral follicles. Oocyte-granulosa cell
      complexes (OGCs) were collected from the early antral follicles of gilts, and
      incubated individually for 14 days in a 96-well culture plate without or with
      PAG. We then evaluated the number of granulosa cells present in OGCs as well as
      the abundance of ATP, lipid, and acetylated lysine in oocytes. OGCs cultured on
      PAG showed significantly greater antrum formation and granulosa cell
      proliferation than controls cultured on standard plastic. Oocytes grown on PAG
      also possessed significantly larger diameter, ATP and lipid content, and lysine
      acetylation, as well as competence to develop to the blastocyst stage.
      Transcriptome analysis of the granulosa cells revealed that genes involved in
      follicular development and mechanosensing are up-regulated under PAG culturing
      conditions. Thus, in vitro culturing OGCs on PAG profoundly induced granulosa
      cell proliferation, resulting in improved developmental competence of the
      oocytes. Mol. Reprod. Dev. 84: 44-54, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27864906
TI  - Role and regulation of Glycogen synthase kinase-3 beta in bovine spermatozoa.
AB  - The serine/threonine kinase Glycogen synthase kinase 3 (GSK-3) is a master switch
      that regulates a multitude of cellular pathways, including the acrosome reaction
      in sperm. In epididymal sperm cells, for example, GSK-3 activity correlates with
      inhibition of motility-yet no direct pathways connecting GSK-3 activation with
      loss of motility have been described. Indeed, the details of how GSK-3 is
      regulated during sperm capacitation and the acrosome reaction remains obscure. To
      this end, we addressed the involvement of the GSK-3 beta isoform in several known
      pathways that contribute to motility and the acrosome reaction. We established
      that Protein kinase A (PKA) is the main regulator of GSK-3beta in sperm, as pre
      treatment of cells with a GSK-3 inhibitor prior to addition of H89, an inhibitor
      of PKA, attenuated the motility loss induced by blocking PKA activity. Both
      induced and spontaneous acrosome reactions also occurred less frequently in sperm
      treated with GSK-3 inhibitors. Finally, we observed a slow decline in
      phosphorylation of GSK-3beta on Ser 9, which represents an inhibited state,
      during sperm capacitation; this phenotype is reversed during the induced acrosome
      reaction, in parallel to activation of Protein phosphatase 1. These results
      suggest that maintenance of sperm motility and acrosome reaction timing are
      mediated by PKA through the regulation of GSK-3 beta activity. Mol. Reprod. Dev.
      84: 8-18, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27864907
TI  - Stimulation effects of ciprofloxacin and sulphamethoxazole in Microcystis
      aeruginosa and isobaric tag for relative and absolute quantitation-based
      screening of antibiotic targets.
AB  - Antibiotics are normally regarded as safe to aquatic ecosystems when their
      contamination concentrations are lower than the toxic threshold. This study
      observed the hazard of ciprofloxacin, sulphamethoxazole and their binary mixture
      to the aquatic environment at environmentally relevant concentrations lower than
      the toxic threshold, due to the stimulation on the bloom of Microcystis
      aeruginosa. The enhanced growth of M. aeruginosa, coupled with elevated
      photosynthesis activity, was exerted by 50-200 ng/L of ciprofloxacin, 100-200
      ng/L of sulphamethoxazole and 20-100 ng/L of the binary antibiotic mixture.
      Stimulated production and release of microcystins were observed at even lower
      concentrations. The upregulation of transcription-related proteins, cell division
      related proteins, a gas vesicle protein, a global nitrogen regulator (ntcA), two
      microcystin synthetases (mcyC and mcyH) and ATP-binding cassette transporters
      provided direct proteomic evidence for the regulation of target antibiotics on M.
      aeruginosa bloom. Cytochrome P450 was an essential component involved in stress
      responses and antibiotic biodegradation. Proteomic responses to antibiotic
      exposure presented a shift in the energy metabolism of M. aeruginosa towards the
      excitation of photosynthesis, an increase of carbohydrate biosynthesis and the
      inhibition of carbohydrate catabolism. Superoxide dismutase, enolase and D1
      protein were candidate target proteins of different antibiotics in M. aeruginosa.
      The antibiotic mixture showed a greater hazard than single antibiotics, and a
      safe threshold of 5 ng/L was suggested for each target antibiotic under the
      coexistence condition.

PMID- 27864909
TI  - The mechanism of CIRP in inhibition of keratinocytes growth arrest and apoptosis
      following low dose UVB radiation.
AB  - UV induces CIRP expression and subsequent Stat3 activation, but the biological
      function and mechanism of CIRP and Stat3 in mediating UVB-induced skin
      carcinogenesis have not been fully elucidated. In this study, we demonstrate that
      CIRP is elevated in all tested melanoma and non-melanoma skin cancer cell lines;
      and the expression of CIRP is upregulated in keratinocytes after being irradiated
      with relatively low dose (<5 mJ/cm2 ), but not high dose (50 mJ/cm2 ), UVB
      acutely and chronically. The increased expression of CIRP, either induced by UVB
      or through overexpression, leads to resistance of keratinocytes to UVB-induced
      growth arrest and death; and reduced expression of CIRP by RNA knockdown
      sensitizes keratinocyte cells to the low dose UVB radiation. We also demonstrated
      that CIRP expression is required for the low dose UVB-induced Tyr705
      phosphorylation, but not total amount, of Stat3. The p-Stat3 level is correlated
      with the expression levels of cyclin D1 and VEGF, two known downstream cell
      growth regulators of Stat3, as well as Bag-1/S, an apoptosis regulator.
      Inhibition of Stat3 DNA-binding activity by S3I-201 leads to a reduction of the p
      Stat3 and Bag-1/S along with growth and survival of keratinocytes post-UVB; and
      the effect of S3I-201 on the UVB-irradiated cells can be partially inhibited by
      overexpression of CIRP or Bag-1/S. Furthermore, the overexpression of Bag-1/S can
      totally inhibit UVB-induced PARP cleavage and caspase 3 activation. The results
      presented above led us to propose that CIRP-p(705)Stat3 cascade promotes cell
      proliferation and survival post-UVB via upregulating the expression of cyclin D1
      and Bag-1/S, respectively. Published 2017. This article is a U.S. Government work
      and is in the public domain in the USA.

PMID- 27864908
TI  - E2F transcription factor 2 variants as predictive biomarkers for recurrence risk
      in patients with squamous cell carcinoma of the oropharynx.
AB  - Because E2F transcription factor 2 (E2F2) promoter polymorphisms have been
      implicated in carcinogenesis and prognosis, we investigated associations between
      genetic variants in five E2F2 promoter polymorphisms and recurrence risk of
      squamous cell carcinoma of the oropharynx (SCCOP) in 1 008 patients. A log-rank
      test and multivariable Cox models were used to assess the associations. Compared
      with patients with variant genotypes of E2F2-rs2742976 and E2F2-rs3218123,
      patients with common homozygous genotypes had better disease-free survival (both
      log-rank, P < 0.001) and lower SCCOP recurrence risk (HR, 0.4, 95% CI, 0.3-0.6
      and HR, 0.3, 95% CI, 0.2-0.5, respectively) after multivariable adjustment.
      Furthermore, among patients with HPV16-positive tumors, those with common
      homozygous genotypes of E2F2-rs2742976 and E2F2-rs3218123 had better disease-free
      survival rates (both log-rank, P < 0.001) and lower recurrence risk (HR, 0.1, 95%
      CI, 0.1-0.4 and HR, 0.1, 95% CI, 0.0-0.2, respectively) than patients with
      variant genotypes. However, no significant differences were found for the other
      three polymorphisms. After combining the risk genotypes of the five polymorphisms
      and using the high-risk group (2-5 risk genotypes) as the reference group, we
      found that the low-risk groups (0 or 1 risk genotype) had significantly lower
      recurrence risk among all patients (HR, 0.4, 95% CI, 0.3-0.6) and among HPV16
      positive patients (HR, 0.2, 95% CI, 0.1-0.5). Our findings suggest that E2F2
      polymorphisms may individually or jointly modify SCCOP recurrence risk,
      particularly for SCCOP patients with HPV16-positive tumors. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 27864910
TI  - Genomic islands of divergence linked to ecotypic variation in sockeye salmon.
AB  - Regions of the genome displaying elevated differentiation (genomic islands of
      divergence) are thought to play an important role in local adaptation, especially
      in populations experiencing high gene flow. However, the characteristics of these
      islands as well as the functional significance of genes located within them
      remain largely unknown. Here, we used data from thousands of SNPs aligned to a
      linkage map to investigate genomic islands of divergence in three ecotypes of
      sockeye salmon (Oncorhynchus nerka) from a single drainage in southwestern
      Alaska. We found ten islands displaying high differentiation among ecotypes.
      Conversely, neutral structure observed throughout the rest of the genome was low
      and not partitioned by ecotype. One island on linkage group So13 was particularly
      large and contained six SNPs with FST  > 0.14 (average FST of neutral SNPs =
      0.01). Functional annotation revealed that the peak of this island contained a
      nonsynonymous mutation in a gene involved in growth in other species (TULP4). The
      islands that we discovered were relatively small (80-402 Kb), loci found in
      islands did not show reduced levels of diversity, and loci in islands displayed
      slightly elevated linkage disequilibrium. These attributes suggest that the
      islands discovered here were likely generated by divergence hitchhiking; however,
      we cannot rule out the possibility that other mechanisms may have produced them.
      Our results suggest that islands of divergence serve an important role in local
      adaptation with gene flow and represent a significant advance towards
      understanding the genetic basis of ecotypic differentiation.

PMID- 27864911
TI  - Spatio-temporal variation in parasite communities maintains diversity at the
      major histocompatibility complex class IIbeta in the endangered Rio Grande
      silvery minnow.
AB  - Climate change will strongly impact aquatic ecosystems particularly in arid and
      semi-arid regions. Fish-parasite interactions will also be affected by predicted
      altered flow and temperature regimes, and other environmental stressors. Hence,
      identifying environmental and genetic factors associated with maintaining
      diversity at immune genes is critical for understanding species' adaptive
      capacity. Here, we combine genetic (MHC class IIbeta and microsatellites),
      parasitological and ecological data to explore the relationship between these
      factors in the remnant wild Rio Grande silvery minnow (Hybognathus amarus)
      population, an endangered species found in the southwestern United States.
      Infections with multiple parasites on the gills were observed and there was
      spatio-temporal variation in parasite communities and patterns of infection among
      individuals. Despite its highly endangered status and chronically low genetic
      effective size, Rio Grande silvery minnow had high allelic diversity at MHC class
      IIbeta with more alleles recognized at the presumptive DAB1 locus compared to the
      DAB3 locus. We identified significant associations between specific parasites and
      MHC alleles against a backdrop of generalist parasite prevalence. We also found
      that individuals with higher individual neutral heterozygosity and higher amino
      acid divergence between MHC alleles had lower parasite abundance and diversity.
      Taken together, these results suggest a role for fluctuating selection imposed by
      spatio-temporal variation in pathogen communities and divergent allele advantage
      in maintenance of high MHC polymorphism. Understanding the complex interaction of
      habitat, pathogens and immunity in protected species will require integrated
      experimental, genetic and field studies.

PMID- 27864912
TI  - Inferring contemporary and historical genetic connectivity from juveniles.
AB  - Measuring population connectivity is a critical task in conservation biology.
      While genetic markers can provide reliable long-term historical estimates of
      population connectivity, scientists are still limited in their ability to
      determine contemporary patterns of gene flow, the most practical time frame for
      management. Here, we tackled this issue by developing a new approach that only
      requires juvenile sampling at a single time period. To demonstrate the usefulness
      of our method, we used the Speartooth shark (Glyphis glyphis), a critically
      endangered species of river shark found only in tropical northern Australia and
      southern Papua New Guinea. Contemporary adult and juvenile shark movements,
      estimated with the spatial distribution of kin pairs across and within three
      river systems, was contrasted with historical long-term connectivity patterns,
      estimated from mitogenomes and genome-wide SNP data. We found strong support for
      river fidelity in juveniles with the within-cohort relationship analysis. Male
      breeding movements were highlighted with the cross-cohort relationship analysis,
      and female reproductive philopatry to the river systems was revealed by the
      mitogenomic analysis. We show that accounting for juvenile river fidelity and
      female philopatry is important in population structure analysis and that targeted
      sampling in nurseries and juvenile aggregations should be included in the genomic
      toolbox of threatened species management.

PMID- 27864913
TI  - Human Secretory IgM Antibodies Activate Human Complement and Offer Protection at
      Mucosal Surface.
AB  - IgM molecules circulate in serum as large polymers, mainly pentamers, which can
      be transported by the poly-Ig receptor (pIgR) across epithelial cells to mucosal
      surfaces and released as secretory IgM (SIgM). The mucosal SIgM molecules have
      non-covalently attached secretory component (SC), which is the extracellular part
      of pIgR which is cleaved from the epithelial cell membrane. Serum IgM antibodies
      do not contain SC and have previously been shown to make a conformational change
      from 'a star' to a 'staple' conformation upon reaction with antigens on a cell
      surface, enabling them to activate complement. However, it is not clear whether
      SIgM similarly can induce complement activation. To clarify this issue, we
      constructed recombinant chimeric (mouse/human) IgM antibodies against hapten 5
      iodo-4-hydroxy-3-nitro-phenacetyl (NIP) and in addition studied polyclonal IgM
      formed after immunization with a meningococcal group B vaccine. The monoclonal
      and polyclonal IgM molecules were purified by affinity chromatography on a column
      containing human SC in order to isolate joining-chain (J-chain) containing IgM,
      followed by addition of excess amounts of soluble SC to create SIgM (IgM J+ SC+).
      These SIgM preparations were tested for complement activation ability and shown
      to be nearly as active as the parental IgM J+ molecules. Thus, SIgM may offer
      protection against pathogens at mucosal surface by complement-mediated cell lysis
      or by phagocytosis mediated by complement receptors present on effector cells on
      mucosa.

PMID- 27864914
TI  - The lek mating system of the worm pipefish (Nerophis lumbriciformis): a molecular
      maternity analysis and test of the phenotype-linked fertility hypothesis.
AB  - The origin and maintenance of mating preferences continues to be an important and
      controversial topic in sexual selection research. Leks and lek-like mating
      systems, where individuals gather in particular spots for the sole purpose of
      mate choice, are particularly puzzling, because the strong directional selection
      imposed by mate choice should erode genetic variation among competing individuals
      and negate any benefit for the choosing sex. Here, we take advantage of the lek
      like mating system of the worm pipefish (Nerophis lumbriciformis) to test the
      phenotype-linked fertility hypothesis for the maintenance of mating preferences.
      We use microsatellite markers to perform a parentage analysis, along with a mark
      recapture study, to confirm that the worm pipefish has an unusual mating system
      that strongly resembles a female lek, where females display and males visit the
      lek to choose mates. Our results show that the most highly ornamented females
      occupy positions near the centre of the breeding area, and males mating with
      these females receive fuller broods with larger eggs compared to males mating
      with less-ornamented females. We also conduct a laboratory experiment to show
      that female ornaments are condition-dependent and honestly signal reproductive
      potential. Overall, these results are consistent with the predictions of a sex
      independent version of the phenotype-linked fertility hypothesis, as male
      preference for female ornaments correlates with fertility benefits.

PMID- 27864915
TI  - Identification of Emergency Department Visits in Medicare Administrative Claims:
      Approaches and Implications.
AB  - OBJECTIVES: Administrative claims data sets are often used for emergency care
      research and policy investigations of healthcare resource utilization, acute care
      practices, and evaluation of quality improvement interventions. Despite the high
      profile of emergency department (ED) visits in analyses using administrative
      claims, little work has evaluated the degree to which existing definitions based
      on claims data accurately captures conventionally defined hospital-based ED
      services. We sought to construct an operational definition for ED visitation
      using a comprehensive Medicare data set and to compare this definition to
      existing operational definitions used by researchers and policymakers. METHODS:
      We examined four operational definitions of an ED visit commonly used by
      researchers and policymakers using a 20% sample of the 2012 Medicare Chronic
      Condition Warehouse (CCW) data set. The CCW data set included all Part A
      (hospital) and Part B (hospital outpatient, physician) claims for a nationally
      representative sample of continuously enrolled Medicare fee-for-services
      beneficiaries. Three definitions were based on published research or existing
      quality metrics including: 1) provider claims-based definition, 2) facility
      claims-based definition, and 3) CMS Research Data Assistance Center (ResDAC)
      definition. In addition, we developed a fourth operational definition (Yale
      definition) that sought to incorporate additional coding rules for identifying ED
      visits. We report levels of agreement and disagreement among the four
      definitions. RESULTS: Of 10,717,786 beneficiaries included in the sample data
      set, 22% had evidence of ED use during the study year under any of the ED visit
      definitions. The definition using provider claims identified a total of 4,199,148
      ED visits, the facility definition 4,795,057 visits, the ResDAC definition
      5,278,980 ED visits, and the Yale definition 5,192,235 ED visits. The Yale
      definition identified a statistically different (p < 0.05) collection of ED
      visits than all other definitions including 17% more ED visits than the provider
      definition and 2% fewer visits than the ResDAC definition. Differences in ED
      visitation counts between each definition occurred for several reasons including
      the inclusion of critical care or observation services in the ED, discrepancies
      between facility and provider billing regulations, and operational decisions of
      each definition. CONCLUSION: Current operational definitions of ED visitation
      using administrative claims produce different estimates of ED visitation based on
      the underlying assumptions applied to billing data and data set availability.
      Future analyses using administrative claims data should seek to validate specific
      definitions and inform the development of a consistent, consensus ED visitation
      definitions to standardize research reporting and the interpretation of policy
      interventions.

PMID- 27864916
TI  - Enhanced contractility of intraparenchymal arterioles after global cerebral
      ischaemia in rat - new insights into the development of delayed cerebral
      hypoperfusion.
AB  - AIM: Delayed cerebral hypoperfusion is a secondary complication found in the days
      after transient global cerebral ischaemia that worsens the ischaemic damage
      inflicted by the initial transient episode of global cerebral ischaemia. A recent
      study demonstrated increased cerebral vasoconstriction in the large arteries on
      the brain surface (pial arteries) after global cerebral ischaemia. However,
      smaller arterioles inside the brain (parenchymal arterioles) are equally
      important in the regulation of cerebral blood flow and yet their pathophysiology
      after global cerebral ischaemia is largely unknown. Therefore, we investigated
      whether increased contractility occurs in the intraparenchymal arterioles.
      METHODS: Global cerebral ischaemia was induced in male Wistar rats by bilateral
      common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral
      blood flow was determined by quantitative autoradiography. Intraparenchymal
      arterioles were isolated and pressurized, and concentration-response curves to
      endothelin-1 with and without the endothelin B receptor-selective antagonist
      BQ788 was generated. Endothelin B receptor expression was investigated by
      quantitative flow cytometry and immunohistochemistry. RESULTS: We observed
      increased endothelin-1-mediated contractility of parenchymal arterioles
      correlating with reduced cerebral blood flow of the cortex, hippocampus and
      caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1
      mediated contractility was abolished by BQ788, and the vascular smooth muscle
      cell-specific expression of endothelin B receptors was significantly increased
      after global cerebral ischaemia. CONCLUSION: Increased endothelin-1-mediated
      contractility and expression of endothelin B receptors in the intraparenchymal
      vasculature contributes to the development of delayed cerebral hypoperfusion
      after global cerebral ischaemia in combination with vascular changes of the pial
      vasculature.

PMID- 27864917
TI  - Genetic variation in the miR-708 gene and its binding targets in bipolar
      disorder.
AB  - OBJECTIVE: rs12576775 was found to be associated with bipolar disorder (BD) in a
      genome-wide association study (GWAS). The GWAS signal implicates genes for the
      microRNAs miR-708 and miR-5579 and the first exon of the Odd Oz/ten-m homolog 4
      gene (ODZ4). In the present study, miR-708, its surrounding region, and its
      targets were analyzed for potential BD-associated functional variants. METHODS:
      The miR-708 gene and surrounding regions were screened for variation using high
      resolution melting (HRM) analysis in 1099 cases of BD, followed by genotyping of
      rare variants in an enlarged sample of 2078 subjects with BD, 1303 subjects with
      schizophrenia, and 1355 healthy controls. Whole-genome sequencing data from 99
      subjects with BD were analyzed for variation in potential miR-708 binding sites.
      The minor allele frequencies (MAFs) of these variants were compared with those
      reported in reference individuals. RESULTS: Three variants detected by HRM were
      selected to be genotyped. rs754333774 was detected in three cases of BD, two
      cases of schizophrenia, and no controls. This variant is located 260 base pairs
      upstream from miR-708 and may play a role in controlling the expression of the
      miR. Four variants were identified in miR-708 targets binding sites. The MAFs of
      each of these variants were similar in BD and reference samples. CONCLUSIONS: We
      report a single recurrent variant located near the miR-708 gene that may have a
      role in BD and schizophrenia susceptibility. These findings await replication in
      independent cohorts, as do functional analyses of the potential consequences of
      this variant.

PMID- 27864918
TI  - How prior preferences determine decision-making frames and biases in the human
      brain.
AB  - Understanding how option values are compared when making a choice is a key
      objective for decision neuroscience. In natural situations, agents may have a
      priori on their preferences that create default policies and shape the neural
      comparison process. We asked participants to make choices between items belonging
      to different categories (e.g., jazz vs. rock music). Behavioral data confirmed
      that the items taken from the preferred category were chosen more often and more
      rapidly, which qualified them as default options. FMRI data showed that baseline
      activity in classical brain valuation regions, such as the ventromedial
      Prefrontal Cortex (vmPFC), reflected the strength of prior preferences. In
      addition, evoked activity in the same regions scaled with the default option
      value, irrespective of the eventual choice. We therefore suggest that in the
      brain valuation system, choices are framed as comparisons between default and
      alternative options, which might save some resource but induce a decision bias.

PMID- 27864919
TI  - Using a novel assessment of procedural proficiency provides medical educators
      insight into blood pressure measurement.
AB  - Objective: This investigation was performed to determine how students in a health
      sciences program utilize and explain techniques within blood pressure measurement
      using a novel assessment, and changes associated with greater curricular
      exposure. Methods: An exploratory, qualitative and quantitative study was
      conducted using a 'Think Aloud' design with protocol analysis. Following
      familiarization, participants performed the task of measuring blood pressure on a
      reference subject while stating their thought processes. A trained practitioner
      recorded each participant's procedural proficiency using a standardized rubric.
      There were 112 participants in the study with varying levels of curricular
      exposure to blood pressure measurement. Results: Four trends are noted.
      Specifically, a trend was observed wherein a marked increase in procedural
      proficiency with a plateau occurred (e.g. released cuff pressure 2-4 mmHg, 10%,
      60%, 83%, 82%). Secondly, a trend was observed with improvement across groups
      (e.g. cuff placed snugly/smoothly on upper arm, 20%, 60%, 81%, and 91%). Other
      trends included a marked improvement with subsequent decrease, and an improvement
      without achieving proficiency (e.g. palpation of the brachial pulse, 5%, 90%,
      81%, 68%, appropriate size cuff, 17%, 40%, 33%, 41%, respectively).
      Qualitatively, transcript interpretation resulted in a need for clarification in
      the way blood pressure procedure is instructed in the curriculum. Conclusions:
      The current investigation provides a snapshot of proficiency in blood pressure
      assessment across a curriculum and highlights considerations for best
      instructional practices, including the use of Think Aloud. Consequently, medical
      educators should use qualitative and quantitative assessments concurrently to
      determine achievement of blood pressure skill proficiency.

PMID- 27864920
TI  - Design of small molecule inhibitors of type III secretion system ATPase EscN from
      enteropathogenic Escherichia coli.
AB  - Enteropathogenic E. coli (EPEC) is a human pathogen using type III secretion
      system for delivery of proteins directly into the human host. The system contains
      a single ATPase, EscN, which is essential for uncoupling of proteins from their
      complexes with chaperones before the delivery. The structure of EscN ATPase (PDB
      code: 2obm) was used to screen computationally for small molecule inhibitors
      blocking its active site. Two lead candidates were examined but only one,
      Compound 54, was selected for further optimization. After extended QSAR
      optimization, two derivatives were found to be competitive inhibitors of EscN
      capable of blocking ATPase activity with a Ki below 50 uM. One candidate, WEN05
      03, with a Ki=16+/-2 uM, was also minimally toxic to mammalian cells as
      determined by other assays. In the cell infection model of HeLa cells with EPEC,
      Compound WEN05-03 completely blocked actin cluster formation at 100 uM
      concentration, when analyzed by confocal microscopy. The second best inhibitor of
      EscN ATPase activity was WEN04-34 with a Ki=46+/-2 uM. However, the compound was
      highly toxic to the BALB/3T3 cell line. In summary, the work identifies a
      compound blocking bacterial ATPase in its active site without causing cellular
      toxicity to the host cells. It is the first report showing feasibility of using
      bacterial virulence system ATPase as a target for safe, non-toxic compounds and
      offering a proof-of-concept for non-antibiotic alternatives.

PMID- 27864922
TI  - Estimates of local biodiversity change over time stand up to scrutiny.
AB  - We present new data and analyses revealing fundamental flaws in a critique of two
      recent meta-analyses of local-scale temporal biodiversity change. First, the
      conclusion that short-term time series lead to biased estimates of long-term
      change was based on two errors in the simulations used to support it. Second, the
      conclusion of negative relationships between temporal biodiversity change and
      study duration was entirely dependent on unrealistic model assumptions, the use
      of a subset of data, and inclusion of one outlier data point in one study. Third,
      the finding of a decline in local biodiversity, after eliminating post
      disturbance studies, is not robust to alternative analyses on the original data
      set, and is absent in a larger, updated data set. Finally, the undebatable point,
      noted in both original papers, that studies in the ecological literature are
      geographically biased, was used to cast doubt on the conclusion that, outside of
      areas converted to croplands or asphalt, the distribution of biodiversity trends
      is centered approximately on zero. Future studies may modify conclusions, but at
      present, alternative conclusions based on the geographic-bias argument rely on
      speculation. In sum, the critique raises points of uncertainty typical of all
      ecological studies, but does not provide an evidence-based alternative
      interpretation.

PMID- 27864923
TI  - 3D bioengineered tissues: From advancements in in vitro safety to new horizons in
      disease modeling.
AB  - Research aimed at more fully emulating human biology in vitro has rapidly
      progressed in recent years with advancements in 3D tissue engineering and
      microphysiological systems. The initial target of such systems has been directed
      towards drug and chemical safety assessment, with the goal of improving
      sensitivity and predictive capabilities. Here we discuss recent developments of
      in vitro organ culture systems, and their future applications in modeling human
      disease.

PMID- 27864921
TI  - What is the role of retroperitoneal exploration in optimally debulked stage IIIC
      epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary
      data study.
AB  - BACKGROUND: The purpose of this study was to determine the effect of
      retroperitoneal (RP) exploration on progression-free survival (PFS) and overall
      survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease
      who underwent optimal debulking surgery. METHODS: Data were collected from
      records of the Gynecologic Oncology Group 182 (GOG-182) study of stage IIIC EOC
      patients cytoreduced to no gross residual disease (R0) or minimal gross residual
      (<1 cm) disease (MGRD) at primary surgery. Patients with stage IIIC disease by
      intraperitoneal (IP) tumor were included and divided into 3 groups: 1) > 2 cm IP
      tumor without lymph node involvement (IP/RP-), 2) > 2 cm IP tumor with lymph node
      involvement (IP/RP+), and 3) > 2 cm IP tumor with no RP exploration (IP/RP?). The
      effects of disease distribution and RP exploration on PFS and OS were assessed
      using Kaplan-Meier and proportional hazards methods. RESULTS: There were 1871
      stage IIIC patients in GOG-182 who underwent optimal primary debulking surgery.
      Of these, 689 (36.8%) underwent RP exploration with removal of lymph nodes from
      at least 1 para-aortic site, and 1182 (63.2%) did not. There were 269 patients in
      the IP/RP- group, 420 patients in the IP/RP + group, and 1182 patients in the
      IP/RP? group. Improved PFS (18.5 vs 16.0 months; P < .0001) and OS (53.3 vs 42.8
      months; P < .0001) were associated with RP exploration versus no exploration.
      Patients with MGRD had improved PFS (16.8 vs 15.1 months, P = 0.0108) and OS
      (44.9 vs 40.5 months, P = 0.0076) versus no exploration. CONCLUSIONS: RP
      exploration at the time of primary surgery in patients with optimally debulked
      stage IIIC EOC is associated with a survival benefit. Cancer 2017;123:985-93. (c)
      2016 American Cancer Society.

PMID- 27864925
TI  - Drug-induced pyoderma gangrenosum: a model to understand the pathogenesis of
      pyoderma gangrenosum.
AB  - Pyoderma gangrenosum (PG) is a rare autoinflammatory condition in which the
      alteration of neutrophil function and the innate immune response play key roles
      in its pathogenesis. Cases of PG have been reported in patients being treated
      with certain medications, which may help us to understand some of the possible
      pathways involved in the aetiology of PG. The aim of this review is to review the
      cases of PG triggered by certain drugs and try to thoroughly understand the
      pathogenesis of the disease. To accomplish this, a PubMed search was completed
      using the following words: pyoderma gangrenosum, neutrophilic dermatosis,
      pathophysiology, drug-induced pyoderma gangrenosum. In total, we found 43 cases
      of drug-induced PG. Most of them were caused by colony-stimulating factors and
      small-molecule tyrosine kinase inhibitors. We propose that drugs induce PG
      through various mechanisms such as dysfunctional neutrophil migration and
      function, dysregulated inflammatory response, promotion of keratinocyte apoptosis
      and alteration of epigenetic mechanisms. PG is a rare condition with complex
      pathophysiology and drug-induced cases are even more scarce; this is the main
      limitation of this review. Understanding the possible mechanisms of drug-induced
      PG, via abnormal neutrophil migration and function, abnormal inflammation,
      keratinocyte apoptosis and alteration of epigenetic mechanisms would help to
      better understand the pathogenesis of PG and ultimately to optimize targeted
      therapy.

PMID- 27864926
TI  - Synaptic distribution of individually labeled mitral cells in the external
      plexiform layer of the mouse olfactory bulb.
AB  - Mitral cells are the major projection neurons of the olfactory bulb. They receive
      olfactory inputs, regulate information, and project their axons to the olfactory
      cortex. To understand output regulation of mitral cells better, we established a
      method to visualize individual projection neurons and quantitatively examined
      their synaptic distribution. Individual mitral cells were labeled by viral
      injection, reconstructed three dimensionally with light microscopy, and serial
      sectioned for electron microscopy. Synaptic distributions were analyzed in
      electron microscopically reconstructed cell bodies, two regions of secondary
      dendrites (near the somata and ~200 MUm from the somata), and primary dendrites.
      The ratio of presynaptic sites (60%) and reciprocal synapses (60% presynaptic and
      80% postsynaptic sites) were similar in each region. Characteristically, primary
      dendrite synapses were distributed mainly within the inner half of the external
      plexiform layer (EPL). For comparison, tufted cells were also examined, and the
      synaptic distribution in two secondary dendrite regions, which corresponded with
      mitral cells, was analyzed. The results showed that the ratio of reciprocal
      synapses (80% presynaptic and 90% postsynaptic sites) was greater than in mitral
      cells. The distribution of symmetrical synapses was also analyzed with synaptic
      and neuronal markers, such as parvalbumin, vesicular gamma-aminobutyric acid
      transporter, and gephyrin. Parvalbumin-expressing neurons tended to form synapses
      on secondary dendrites near the somata and were more uniformly distributed on
      primary dendrites of mitral cells. These results indicate that local mitral cell
      synaptic circuits are formed in accordance with their functional roles and
      restricted to the inner half of the EPL. J. Comp. Neurol. 525:1633-1648, 2017.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27864927
TI  - Indications for major hepatectomy and combined procedures for advanced
      gallbladder cancer.
AB  - BACKGROUND: The clinical impact of major hepatectomy for advanced gallbladder
      cancer is currently unclear. METHODS: Patients who underwent resection for stage
      II, III or IV gallbladder cancer were enrolled. The surgical outcomes of patients
      who underwent major hepatectomy were compared with those of patients treated with
      minor hepatectomy and those with unresectable gallbladder cancer. The clinical
      impact of major hepatectomy and combined advanced procedures such as portal vein
      resection or pancreatoduodenectomy for advanced gallbladder cancer were
      evaluated. RESULTS: A total of 96 patients were enrolled; 29 patients underwent
      major and 67 had minor hepatectomy. The overall morbidity rate was higher in the
      major hepatectomy group (55 versus 27 per cent; P = 0.022). There were no deaths
      after major hepatectomy. Overall survival was better in the major hepatectomy
      group than in the group of 15 patients with unresectable disease (median survival
      17.7 versus 11.4 months; P = 0.003). In a subgroup analysis of the major
      hepatectomy group, liver metastasis (P = 0.038) and hepatic arterial invasion (P
      = 0.017) were independently associated with overall survival. Overall survival in
      patients with liver metastasis (P = 0.572) or hepatic arterial invasion (P =
      0.776) was comparable with that in the unresectable group. However, overall
      survival among patients with lymph node metastasis (P = 0.062) or following
      portal vein resection (P = 0.054) or pancreatoduodenectomy (P = 0.011) was better
      than in the unresectable group. CONCLUSION: Major hepatectomy combined with
      portal vein resection or pancreatoduodenectomy, if necessary, may be considered
      in the treatment of advanced gallbladder cancer, especially in selected patients
      without liver metastasis or hepatic arterial invasion.

PMID- 27864928
TI  - Classification of Porcine Cranial Fracture Patterns Using a Fracture Printing
      Interface,<sup/>.
AB  - Distinguishing between accidental and abusive head trauma in children can be
      difficult, as there is a lack of baseline data for pediatric cranial fracture
      patterns. A porcine head model has recently been developed and utilized in a
      series of studies to investigate the effects of impact energy level, surface
      type, and constraint condition on cranial fracture patterns. In the current
      study, an automated pattern recognition method, or a fracture printing interface
      (FPI), was developed to classify cranial fracture patterns that were associated
      with different impact scenarios documented in previous experiments. The FPI
      accurately predicted the energy level when the impact surface type was rigid.
      Additionally, the FPI was exceedingly successful in determining fractures caused
      by skulls being dropped with a high-level energy (97% accuracy). The FPI,
      currently developed on the porcine data, may in the future be transformed to the
      task of cranial fracture pattern classification for human infant skulls.

PMID- 27864924
TI  - Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial.
AB  - BACKGROUND: The long pentraxin PTX3 is a key component of the humoral arm of
      innate immunity related to sepsis severity and mortality. We evaluated the
      clinical and prognostic significance of circulating PTX3 in the largest cohort
      ever reported of patients with severe sepsis or septic shock. MATERIALS AND
      METHODS: Plasma PTX3 was measured on days 1, 2 and 7 after randomization of 958
      patients to albumin or crystalloids for fluid resuscitation in the multicentre
      Albumin Italian Outcome Sepsis (ALBIOS) trial. We tested the association of PTX3
      and its changes over time with clinical severity, prevalent and incident organ
      dysfunctions, 90-day mortality and treatment. RESULTS: PTX3 was high at baseline
      (72 [33-186] ng/mL) and rose with the severity and number of organ dysfunctions
      (P < 0.001) and the incidence of subsequent new failures. The PTX3 concentration
      dropped from day 1 to 7, but this decrease was less pronounced in patients with
      septic shock (P = 0.0004). Higher concentrations of PTX3 on day 1 predicted
      incident organ dysfunctions. Albumin supplementation was associated with lower
      levels of PTX3 in patients with septic shock (P = 0.005) but not in those without
      shock. In a fully adjusted multivariable model, PTX3 on day 7 predicted 90-day
      mortality. Smaller drops in PTX3 predicted higher 90-day mortality. CONCLUSIONS:
      In severe sepsis and septic shock, early high PTX3 predict subsequent new organ
      failures, while a smaller drop in circulating PTX3 over time predicts an
      increased risk of death. Patients with septic shock show lower levels of PTX3
      when assigned to albumin than to crystalloids.

PMID- 27864930
TI  - Patients with atopic dermatitis with filaggrin loss-of-function mutations show
      good but lower responses to immunosuppressive treatment.

PMID- 27864929
TI  - Temporal lobe epilepsy and focal cortical dysplasia in children: A tip to find
      the abnormality.
AB  - OBJECTIVE: To demonstrate an association between magnetic resonance imaging (MRI)
      findings and pathologic characteristics in children who had surgery for medically
      refractory epilepsy due to focal cortical dysplasia (FCD). METHODS: We
      retrospectively studied 110 children who had epilepsy surgery. Twenty-seven
      patients with FCD were included. Thirteen had temporal lobe epilepsy (TLE) and 14
      had extra-temporal lobe epilepsy (ETLE). Three patients had associated mesial
      temporal sclerosis. Preoperative 3T MRIs interleaved with nine controls were
      blindly re-reviewed and categorized according to signal alteration. Pathologic
      specimens were classified according to the 2011 International League Against
      Epilepsy (ILAE) classification and compared to MRI studies. RESULTS: Rates of
      pathology subtypes differed between TLE and ETLE (chi2 (3) = 8.57, p = 0.04). FCD
      type I was more frequent in TLE, whereas FCD type II was more frequent in ETLE.
      In the TLE group, nine patients had temporal tip abnormalities. They all
      exhibited gray-white matter blurring with decreased myelination and white matter
      hyperintense signal. Blurring involved the whole temporal tip, not just the area
      of dysplasia. These patients were less likely to demonstrate cortical thickening
      compared to those without temporal tip findings (chi2 (1) = 9.55, p = 0.002).
      Three of them had FCD Ib, three had FCD IIa, two had FCD IIIa, and one had FCD
      IIb; MRI features could not entirely distinguish between FCD subtypes. TLE
      patients showed more pronounced findings than ETLE on MRI (chi2 (1) = 11.95, p =
      0.003, odds ratio [OR] 18.00). In all cases of FCD, isolated blurring was more
      likely to be associated with FCD II, whereas blurring with decreased myelination
      was seen with FCD I (chi2 (6) = 13.07, p = 0.042). SIGNIFICANCE: Our study
      described associations between MRI characteristics and pathology in children with
      FCD and offered a detailed analysis of temporal lobe tip abnormalities and FCD
      subtypes in children with TLE. These findings may contribute to the presurgical
      evaluation of patients with refractory epilepsy.

PMID- 27864931
TI  - Spatial distribution of synapses on tyrosine hydroxylase-expressing
      juxtaglomerular cells in the mouse olfactory glomerulus.
AB  - Olfactory sensory axons converge in specific glomeruli where they form excitatory
      synapses onto dendrites of mitral/tufted (M/T) and juxtaglomerular (JG) cells,
      including periglomerular (PG), external tufted (ET), and superficial-short axon
      cells. JG cells consist of heterogeneous subpopulations with different
      neurochemical, physiological, and morphological properties. Among JG cells,
      previous electron microscopic (EM) studies have shown that the majority of
      synaptic inputs to tyrosine hydroxylase (TH)-immunoreactive neurons were
      asymmetrical synapses from olfactory nerve (ON) terminals. However, recent
      physiological results revealed that 70% of dopaminergic/gamma-aminobutyric acid
      (GABA)ergic neurons received polysynaptic inputs via ET cells, whereas the
      remaining 30% received monosynaptic ON inputs. To understand the discrepancies
      between EM and physiological data, we used serial EM analysis combined with
      confocal laser scanning microscope images to examine the spatial distribution of
      synapses on dendrites using mice expressing enhanced green fluorescent protein
      under the control of the TH promoter. The majority of synaptic inputs to TH
      expressing JG cells were from ON terminals, and they preferentially targeted
      distal dendrites from the soma. On the other hand, the numbers of non-ON inputs
      were fewer and targeted proximal dendrites. Furthermore, individual TH-expressing
      JG cells formed serial synapses, such as M/T->TH->another presumed M/T or ON->TH
      >presumed M/T, but not reciprocal synapses. Serotonergic fibers also associated
      with somatic regions of TH neurons, displaying non-ON profiles. Thus, fewer
      proximal non-ON synapses provide more effective inputs than large numbers of
      distal ON synapses and may occur on the physiologically characterized population
      of dopaminergic-GABAergic neurons (70%) that receive their most effective inputs
      indirectly via an ON->ET->TH circuit. J. Comp. Neurol. 525:1059-1074, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 27864932
TI  - HPV status and favourable outcome in vulvar squamous cancer.
AB  - It is universally accepted that high-risk human papillomavirus (HR-HPV) is the
      cause of cervical dysplasia and cancer. More recently, it has been shown that HPV
      is also a marker of clinical outcome in oropharyngeal cancer. However,
      contemporary information is lacking on both the prevalence of HPV infection in
      vulvar cancer (VSCC), its precursor lesion, vulvar intraepithelial neoplasia
      (VIN) and the influence of HPV-status on the prognosis of this malignancy. We
      have conducted a detailed population-based study to examine rates of progression
      of VIN to VSCC, type-specific HPV prevalence in vulvar disease and the influence
      of HPV status on clinical outcome in VSCC. We observed that the age at which
      women are diagnosed with VSCC is falling and there is a significant time gap
      between first diagnosis of VIN and progression to invasive disease. HR-HPV
      infection was detected in 87% (97/112) cases of VIN and 52% cases (32/62) of
      VSCC. The presence of HR-HPV in squamous intraepithelial lesion was associated
      with lower rates of progression to invasive cancer (hazard ratio, 0.22, p =
      0.001). In the adjusted analysis, HR-HPV was associated with improved progression
      free survival of VSCC compared to those with HPV negative tumours (hazard ratio,
      0.32, p = 0.02).

PMID- 27864933
TI  - Woody plant richness does not influence invertebrate community reassembly
      trajectories in a tree diversity experiment.
AB  - Understanding the relationship between plant diversity and diversity at higher
      trophic levels is important from both conservation and restoration perspectives.
      Although there is strong evidence for bottom-up maintenance of biodiversity, this
      is based largely on studies of simplified grassland systems. Recently, studies in
      the TreeDivNet global network of tree diversity experiments have begun to test
      whether these findings are generalizable to more complex ecosystems, such as
      woodlands. We monitored invertebrate community reassembly over 5 yr of
      experimental woodland restoration at the TreeDivNet Ridgefield site in southwest
      Australia, testing the effects of woody plant species richness and herb-layer
      manipulation on invertebrate community structure and ant species composition.
      From 2010 to 2014, we sampled ground-dwelling invertebrates using pitfall traps
      in herbicide vs. no-herbicide subplots nested within each of 10 woody plant
      treatments varying in richness from zero (bare controls) to eight species, which
      produced a total of 211, 235 invertebrates, including 98, 979 ants belonging to
      74 species. In mixed model analyses, the presence of woody plants was an
      important driver of faunal community reassembly (relative to bare control plots),
      but faunal responses to woody plant treatment combinations were idiosyncratic and
      unrelated to woody plant richness across treatments. We also found that a
      herbicide-induced reduction in herbaceous plant cover and richness had a positive
      effect on ant richness and caused more rapid convergence of invertebrate
      community composition toward the composition of a woodland reference site. These
      findings show that woody plant richness did not have direct positive effects on
      the diversity and community reassembly trajectories of higher trophic levels in
      our woodland system. From a management perspective, this suggests that even low
      diversity restoration or carbon sequestration plantings can potentially lead to
      faunal reassembly outcomes that are comparable to more complex re-planting
      designs.

PMID- 27864934
TI  - Recovery of Trace DNA on Clothing: A Comparison of Mini-tape Lifting and Three
      Other Forensic Evidence Collection Techniques.
AB  - Trace DNA is often found in forensic science investigations. Experience has shown
      that it is difficult to retrieve a DNA profile when trace DNA is collected from
      clothing. The aim of this study was to compare four different DNA collection
      techniques on six different types of clothing in order to determine the best
      trace DNA recovery method. The classical stain recovery technique using a wet
      cotton swab was tested against dry swabbing, scraping and a new method, referred
      to as the mini-tape lifting technique. Physical contact was simulated with three
      different "perpetrators" on 18 machine-washed garments. DNA was collected with
      the four different DNA recovery methods and subjected to standard PCR-based DNA
      profiling. The comparison of STR results showed best results for the mini-tape
      lifting and scraping methods independent of the type of clothing. The new mini
      tape lifting technique proved to be an easy and reliable DNA collection method
      for textiles.

PMID- 27864935
TI  - Adenoid Cystic Carcinoma of the Trachea Resulting in Fatal Asphyxia.
AB  - Primary malignant tumors of the trachea are uncommon. The authors report a case
      of a 72-year-old female who died from asphyxia due to an undiagnosed obstructing
      adenoid cystic carcinoma of the trachea. The decedent became unresponsive while
      eating cereal and was pronounced upon arrival at the local hospital. The autopsy
      revealed a near occlusive tumor mass just superior to the bifurcation of the
      distal trachea. There was no evidence of aspiration. The death was the result of
      asphyxia due to obstruction of the trachea by an adenoid cystic carcinoma. This
      case demonstrates that an obstructive tumor mass may remain undiagnosed until an
      obstructive episode results in a sudden death.

PMID- 27864937
TI  - Pax3 overexpression induces cell aggregation and perturbs commissural axon
      projection during embryonic spinal cord development.
AB  - Pax3 is a transcription factor that belongs to the paired box family. In the
      developing spinal cord it is expressed in the dorsal commissural neurons, which
      project ascending axons contralaterally to form proper spinal cord-brain
      circuitry. While it has been shown that Pax3 induces cell aggregation in vitro,
      little is known about the role of Pax3 in cell aggregation and spinal circuit
      formation in vivo. We have reported that Pax3 is involved in neuron
      differentiation and that its overexpression induces ectopic cadherin-7
      expression. In this study we report that Pax3 overexpression also induces cell
      aggregation in vivo. Tissue sections and open book preparations revealed that
      Pax3 overexpression prevents commissural axons from projecting to the
      contralateral side of the spinal cord. Cells overexpressing Pax3 aggregated in
      cell clusters that contained shortened neurites with perturbed axon growth and
      elongation. Pax3-specific shRNA partially rescued the morphological change
      induced by Pax3 overexpression in vivo. Our results indicate that the normal
      expression of Pax3 is necessary for proper axonal pathway finding and commissural
      axon projection. In conclusion, Pax3 regulates neural circuit formation during
      embryonic development. J. Comp. Neurol. 525:1618-1632, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27864936
TI  - Effect of sphingosine kinase modulators on interleukin-1beta release, sphingosine
      1-phosphate receptor 1 expression and experimental autoimmune encephalomyelitis.
AB  - BACKGROUND AND PURPOSE: The sphingosine analogue, FTY720 (GilenyaR ), alleviates
      clinical disease progression in multiple sclerosis. Here, we variously assessed
      the effects of an azide analogue of (S)-FTY720 vinylphosphonate (compound 5; a
      sphingosine kinase 1 activator), (R)-FTY720 methyl ether (ROMe, a sphingosine
      kinase 2 inhibitor) and RB-020 (a sphingosine kinase 1 inhibitor and sphingosine
      kinase 2 substrate) on IL-1beta formation, sphingosine 1-phosphate levels and
      expression of S1P1 receptors. We also assessed the effect of compound 5 and ROMe
      in an experimental autoimmune encephalomyelitis (EAE) model in mice. EXPERIMENTAL
      APPROACH: We measured IL-1beta formation by macrophages, sphingosine 1-phosphate
      levels and expression levels of S1P1 receptors in vitro and clinical score in
      mice with EAE and the extent of inflammatory cell infiltration into the spinal
      cord in vivo. KEY RESULTS: Treatment of differentiated U937 macrophages with
      compound 5, RB-020 or sphingosine (but not ROMe) enhanced IL-1beta release. These
      data suggest that these compounds might be pro-inflammatory in vitro. However,
      compound 5 or ROMe reduced disease progression and infiltration of inflammatory
      cells into the spinal cord in EAE, and ROMe induced a reduction in CD4+ and CD8+
      T-cell levels in the blood (lymphopenia). Indeed, ROMe induced a marked decrease
      in expression of cell surface S1P1 receptors in vitro. CONCLUSION AND
      IMPLICATIONS: This is the first demonstration that an activator of sphingosine
      kinase 1 (compound 5) and an inhibitor of sphingosine kinase 2 (ROMe, which also
      reduces cell surface S1P1 receptor expression) have an anti-inflammatory action
      in EAE.

PMID- 27864938
TI  - Harms of cervical cancer screening in the United States and the Netherlands.
AB  - We studied harms related to cervical cancer screening and management of screen
      positive women in the United States (US) and the Netherlands. We utilized data
      from four US integrated health care systems (SEARCH), the US National Health
      Interview Survey, New Mexico state, the Netherlands national histopathology
      registry, and included studies on adverse health effects of cervical screening.
      We compared the number of Papanicolaou (Pap) smear tests, abnormal test results,
      punch biopsies, treatments, health problems (anxiety, pain, bleeding and
      discharge) and preterm births associated with excisional treatments. Results were
      age-standardized to the 2007 US population. Based on SEARCH, an estimated 36
      million Pap tests were performed in 2007 for 91 million US women aged 21-65
      years, leading to 2.3 million abnormal Pap tests, 1.5 million punch biopsies, 0.3
      million treatments for precancerous lesions, 5 thousand preterm births and over 8
      million health problems. Under the Netherlands screening practice, fewer Pap
      tests (58%), abnormal test results (64%), punch biopsies (75%), treatment
      procedures (40%), preterm births (60%) and health problems (63%) would have
      occurred. The SEARCH data did not differ much from other US data for 2007 or from
      more recent data up to 2013. Thus compared to the less intensive screening
      practice in the Netherlands, US practice of cervical cancer screening may have
      resulted in two- to threefold higher harms, while the effects on cervical cancer
      incidence and mortality are similar. The results are also of high relevance in
      making recommendations for HPV screening. Systematic collection of harms data is
      needed for monitoring and for better incorporation of harms in making screening
      recommendations.

PMID- 27864939
TI  - GABAergic innervation of the ciliary ganglion in macaque monkeys - A light and
      electron microscopic study.
AB  - The vertebrate ciliary ganglion (CG) is a relay station in the parasympathetic
      pathway activating the iris sphincter and ciliary muscle to mediate pupillary
      constriction and lens accommodation, respectively. While the postganglionic
      motoneurons in the CG are cholinergic, as are their inputs, there is evidence
      from avian studies that GABA may also be involved. Here, we used light and
      electron microscopic methods to examine the GABAergic innervation of the CG in
      Macaca fascicularis monkeys. Immunohistochemistry for the gamma aminobutyric acid
      synthesizing enzyme glutamic acid decarboxylase (GAD) and choline
      acetyltransferase (ChAT) revealed that all CG neurons are contacted by ChAT
      positive terminals. A subpopulation of 17.5% of CG neurons was associated with
      terminal boutons expressing GAD-immunoreactivity in addition. Double-labeling for
      GAD and synaptophysin confirmed that these were synaptic terminals. Electron
      microscopic analysis in conjunction with GABA-immunogold staining showed that (1)
      GAD-positive terminals mainly target dendrites and spines in the perisomatic
      neuropil of CG neurons; (2) GABA is restricted to a specific terminal type, which
      displays intermediate features lying between classically excitatory and
      inhibitory endings; and (3) if a CG neuron is contacted by GABA-positive
      terminals, virtually all perisomatic terminals supplying it show GABA
      immunoreactivity. The source of this GABAergic input and whether GABA contributes
      to a specific CG function remains to be investigated. Nevertheless, our data
      indicate that the innervation of the ciliary ganglion is more complex than
      previously thought, and that GABA may play a neuromodulatory role in the control
      of lens or pupil function. J. Comp. Neurol. 525:1517-1531, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27864941
TI  - Male, old age and low income to predispose epilepsy in migraineurs.
AB  - BACKGROUND: This study investigated whether sex, age, income and any comorbidity
      affect subsequent epilepsy development in migraineurs. MATERIALS AND METHODS: A
      total of 4915 men diagnosed with migraine who were aged older than 20 years were
      identified as the study cohort. A total of 4882 female migraineurs were included
      in the comparison cohort. We calculated the adjusted hazard ratio (aHR) for the
      risk of epilepsy in the two cohorts after adjustment for age and comorbidity.
      Kaplan-Meier analysis was used to analyse the cumulative epilepsy incidence, and
      the log-rank test was used to estimate the differences between the two cumulative
      incidence curves. RESULTS: The risk of epilepsy was 2.31-fold higher in male
      migraineurs than in female migraineurs. The income-specific analysis showed that
      the risk of epilepsy was high in migraineurs with a low monthly income [aHR: 2.73
      for 15 000-25 000 new Taiwan dollar (NTD; approximately 500-833 USD) and aHR:
      2.71 for < 15 000 NTD]. Among patients with one or more comorbidity, a 2.48-fold
      (95% confidence interval: 1.65-3.74) high risk of epilepsy was noted in male
      migraineurs, regardless of the presence of head injury. Additional analyses
      revealed that male migraineurs aged 65 years or older had the highest risk of
      epilepsy. CONCLUSION: Migraineurs have an increased risk of subsequent epilepsy.
      Male sex, old age and low income may interact with migraine and result in a high
      risk of epilepsy in migraineurs.

PMID- 27864942
TI  - A review of capture and post-release mortality of elasmobranchs.
AB  - There is a need to better understand the survivorship of discarded fishes, both
      for commercial stocks and species of conservation concern. Within European
      waters, the landing obligations that are currently being phased in as part of the
      European Union's reformed common fisheries policy means that an increasing number
      of fish stocks, with certain exceptions, should not be discarded unless it can be
      demonstrated that there is a high probability of survival. This study reviews the
      various approaches that have been used to examine the discard survival of
      elasmobranchs, both in terms of at-vessel mortality (AVM) and post-release
      mortality (PRM), with relevant findings summarized for both the main types of
      fishing gear used and by taxonomic group. Discard survival varies with a range of
      biological attributes (species, size, sex and mode of gill ventilation) as well
      as the range of factors associated with capture (e.g. gear type, soak time, catch
      mass and composition, handling practices and the degree of exposure to air and
      any associated change in ambient temperature). In general, demersal species with
      buccal-pump ventilation have a higher survival than obligate ram ventilators.
      Several studies have indicated that females may have a higher survival than
      males. Certain taxa (including hammerhead sharks Sphyrna spp. and thresher sharks
      Alopias spp.) may be particularly prone to higher rates of mortality when caught.

PMID- 27864943
TI  - "Hummingbird" floral traits interact synergistically to discourage visitation by
      bumble bee foragers.
AB  - Pollination syndromes are suites of floral traits presumed to reflect adaptations
      to attract and utilize a "primary" type of animal pollinator. However, syndrome
      traits may also function to deter "secondary" flower visitors that reduce plant
      fitness through their foraging activities. Here we use the hummingbird-pollinated
      plant species Mimulus cardinalis as a model to investigate the potential
      deterrent effects of classic bird syndrome traits on bumble bee foragers. To
      establish that M. cardinalis flowers elicit an avoidance response in bees, we
      assessed the choice behavior of individual foragers on a mixed experimental array
      of M. cardinalis and its bee-pollinated sister species M. lewisii. As expected,
      bees showed a strong preference against M. cardinalis flowers (only 22% of total
      bee visits were to M. cardinalis), but surprisingly also showed a high degree of
      individual specialization (95.2% of total plant transitions were between
      conspecifics). To determine M. cardinalis floral traits that discourage bee
      visitation, we then assessed foraging responses of individuals to M. cardinalis
      like and M. lewisii-like floral models differing in color, orientation, reward,
      and combinations thereof. Across experiments, M. cardinalis-like trait
      combinations consistently produced a higher degree of flower avoidance behavior
      and individual specialization than expected based on bee responses to each trait
      in isolation. We then conducted a series of flower discrimination experiments to
      assess the ability of bees to utilize traits and trait combinations associated
      with each species. Relative to M. lewisii-like alternatives, M. cardinalis-like
      traits alone had a minimal effect on bee foraging proficiency but together
      increased the time bees spent searching for rewarding flowers from 1.49 to 2.65 s
      per visit. Collectively, our results show that M. cardinalis flowers impose
      foraging costs on bumble bees sufficient to discourage visitation and remarkably,
      generate such costs through synergistic color-orientation and color-reward trait
      interactions. Floral syndromes therefore represent complex adaptations to
      multiple pollinator groups, rather than simply the primary pollinator.

PMID- 27864940
TI  - Endogenous lysophosphatidic acid (LPA1 ) receptor agonists demonstrate ligand
      bias between calcium and ERK signalling pathways in human lung fibroblasts.
AB  - BACKGROUND AND PURPOSE: Human lung fibroblasts (HLF) express high levels of the
      LPA1 receptor, a GPCR that responds to the endogenous lipid mediator,
      lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist
      and have been detected in biological fluids such as serum and plasma. The most
      widely expressed of the LPA receptor family is the LPA1 receptor, which
      predominantly couples to Gq/11 , Gi/o and G12/13 proteins. This promiscuity of
      coupling raises the possibility that some of the LPA analogues may bias the LPA1
      receptor towards one signalling pathway over another. EXPERIMENTAL APPROACH:
      Here, we have explored the signalling profiles of a range of LPA analogues in HLF
      that endogenously express the LPA1 receptor. HLF were treated with LPA analogues
      and receptor activation monitored via calcium mobilization and ERK
      phosphorylation. KEY RESULTS: These analyses demonstrated that the 16:0, 17:0,
      18:2 and C18:1 LPA analogues appear to exhibit ligand bias between ERK
      phosphorylation and calcium mobilization when compared with 18:1 LPA, one of the
      most abundant forms of LPA that has been found in human plasma. CONCLUSION AND
      IMPLICATIONS: The importance of LPA as a key signalling molecule is shown by its
      widespread occurrence in biological fluids and its association with disease
      conditions such as fibrosis and cancer. These findings have important, as yet
      unexplored, implications for the (patho-) physiological signalling of the LPA1
      receptor, as it may be influenced not only by the concentration of endogenous
      ligand but the isoform as well.

PMID- 27864944
TI  - Spatial vegetation patterns and neighborhood competition among woody plants in an
      East African savanna.
AB  - The majority of research on savanna vegetation dynamics has focused on the
      coexistence of woody and herbaceous vegetation. Interactions among woody plants
      in savannas are relatively poorly understood. We present data from a 10-yr
      longitudinal study of spatially explicit growth patterns of woody vegetation in
      an East African savanna following exclusion of large herbivores and in the
      absence of fire. We examined plant spatial patterns and quantified the degree of
      competition among woody individuals. Woody plants in this semiarid savanna
      exhibit strongly clumped spatial distributions at scales of 1-5 m. However,
      analysis of woody plant growth rates relative to their conspecific and
      heterospecific neighbors revealed evidence for strong competitive interactions at
      neighborhood scales of up to 5 m for most woody plant species. Thus, woody plants
      were aggregated in clumps despite significantly decreased growth rates in close
      proximity to neighbors, indicating that the spatial distribution of woody plants
      in this region depends on dispersal and establishment processes rather than on
      competitive, density-dependent mortality. However, our documentation of
      suppressive effects of woody plants on neighbors also suggests a potentially
      important role for tree-tree competition in controlling vegetation structure and
      indicates that the balanced-competition hypothesis may contribute to well-known
      patterns in maximum tree cover across rainfall gradients in Africa.

PMID- 27864946
TI  - Development of a Mobile Toolmark Characterization/Comparison System.
AB  - Since the development of the striagraph, various attempts have been made to
      enhance forensic investigation through the use of measuring and imaging
      equipment. This study describes the development of a prototype system employing
      an easy-to-use software interface designed to provide forensic examiners with the
      ability to measure topography of a toolmarked surface and then conduct various
      comparisons using a statistical algorithm. Acquisition of the data is carried out
      using a portable 3D optical profilometer, and comparison of the resulting data
      files is made using software named "MANTIS" (Mark and Tool Inspection Suite). The
      system has been tested on laboratory-produced markings that include fully
      striated marks (e.g., screwdriver markings), quasistriated markings produced by
      shear-cut pliers, impression marks left by chisels, rifling marks on bullets, and
      cut marks produced by knives. Using the system, an examiner has the potential to
      (i) visually compare two toolmarked surfaces in a manner similar to a comparison
      microscope and (ii) use the quantitative information embedded within the acquired
      data to obtain an objective statistical comparison of the data files. This study
      shows that, based on the results from laboratory samples, the system has great
      potential for aiding examiners in conducting comparisons of toolmarks.

PMID- 27864945
TI  - Risk of nasopharyngeal carcinoma penetrates across immigrant generations: A
      migrant cohort study of 2.3 million Jewish Israeli adolescents.
AB  - Nasopharyngeal cancer (NPC) incidence varies widely across geographic regions and
      ethnic groups. We conducted a large-scale migrant cohort study to assess origin
      and migrant generation as predictors of NPC, controlling for possible
      confounders. Data on 2.3 million Jewish Israeli adolescents, who underwent a
      compulsory general health examination at ages 16-19 between the years 1967 and
      2011 were linked to the Israel National Cancer Registry to obtain incident NPC up
      to 2012. Cox proportional hazards were used to model time to event. During 46.5
      million person-years of follow-up, 276 incident cases were identified. Origin was
      a strong independent predictor of NPC with high rates for first generation North
      African born (adjusted HR 5.52; 95% CI 2.43-12.52; p < 0.000044) and Asian born
      (adjusted HR 3.79; 95% CI 1.43-10.00; p = 0.007) compared to European-born,
      adjusted for sex, year of birth, residential socio-economic position, years of
      education, rural residence, body mass index and height. The magnitude of the
      associations was similar in the Israeli-born of North African and Asian origin,
      with these second and third generation immigrants showing elevated HRs (adjusted
      HR 6.09; 95% CI 2.81-13.20; p = 4.72.10-6 and 3.86; 95% CI 1.77-8.41; p =
      0.00067, respectively). These findings suggest a strong genetic predisposition
      and/or efficient cultural transmission of environmental exposures in the etiology
      of NPC.

PMID- 27864947
TI  - Determining the Toxicological Significance of Pregabalin in Fatalities.
AB  - Pregabalin has become more widely prescribed and abused in recent years but is
      still not always included in laboratory analysis. An LC-MS-MS method has been
      developed and applied to measure pregabalin in 93 postmortem cases, including
      drug-related deaths, alternative causes of death, and fatalities where pregabalin
      was likely to have contributed to death. Other drugs or alcohol was detected, and
      the most common drug types (in decreasing frequency) were antidepressants,
      opioids, benzodiazepines, opiates, alcohol, antipsychotics, cocaine, cardiac
      drugs, amphetamines, cannabis, anticonvulsants, and antihistamines. New
      psychoactive substances (methoxphenidine and synthetic cannabinoids) were only
      found in two cases. The results provide further data to assist in evaluating the
      significance of postmortem pregabalin concentrations and a toxicologically
      significant concentration of 25 mg/L is proposed. Pregabalin, especially with
      concomitant use of other CNS depressant drugs, presents a significant
      toxicological risk and existing laboratory protocols should be reviewed for their
      suitability to detect pregabalin.

PMID- 27864948
TI  - Using Frons Width to Differentiate Blow Fly Species (Diptera: Calliphoridae)
      Phormia regina (Meigen) and Protophormia terraenovae (Robineau-Desvoidy).
AB  - Protophormia terraenovae (Robineau-Desvoidy) (Diptera: Calliphoridae) and Phormia
      regina (Meigen) (Diptera: Calliphoridae) are morphologically similar blow fly
      species commonly used for estimating postmortem intervals. Field collection and
      storage of adults can result in color changes, in particular on calypters and
      palps; often collected specimens show damage such as wing fray or fungal growth.
      We measured the frons width: total head width ratio using photographs (ImageJ
      version 1.49) to differentiate these two species. Both sexes were distinguishable
      to species, with the greatest difference between males: 12.34% P. terraenovae
      versus 1.62% P. regina, less so for females: 40.25% P. terraenovae, versus 33.65%
      P. regina. Incorporating this feature into future blow fly keys would help with
      distinguishing field-caught specimens when other features are obstructed.

PMID- 27864949
TI  - Multimethod Resolution of a Small-Scale Case of Commingling.
AB  - This study highlights the use of multiple methods for resolving a case of
      commingled human remains. Skeletal remains were located in a marijuana field in
      rural northern California by law enforcement. Although initially buried in
      shallow graves, the remains of two decedents were disturbed by large carnivores
      and scattered over a wide area. The remains were submitted by law enforcement for
      forensic anthropological analysis and resolution of commingling. To segregate the
      remains of the two individuals, a number of methods were employed, including: (i)
      physical matching of fragmented remains; (ii) articulation to evaluate joint
      congruence; (iii) visual pair-matching of bilateral elements; (iv) osteometric
      pair-matching; (v) evaluation of taphonomic patterns; (vi) DNA analysis; and
      (vii) portable X-ray spectrometry (pXRF). This multimethod approach resulted in
      accurate resolution of the commingling and facilitated reconstruction of the
      biological profiles, taphonomic patterns, and trauma analysis for each
      individual.

PMID- 27864950
TI  - The Impact of Freezing on Bone Mineral Density: Implications for Forensic
      Research.
AB  - It is common for researchers using animal or human remains for scientific study
      to freeze samples prior to use. However, effects of freezing on bone macro- or
      microstructure are relatively unknown. The research objective of this study was
      to determine whether freezing could potentially bias experimental results by
      analyzing changes in bone mineral density (BMD) with the freezing of remains over
      time. Eight fetal pigs were scanned to determine their initial BMD before
      freezing. Three piglets underwent a freeze-thaw cycle to assess the effects of
      the freezing process. Four piglets were frozen and scanned weekly for 20 weeks to
      assess freezing over time. The overall average between the fresh initial scan and
      final frozen scan was significantly different (p < 0.001). Per contra, the final
      thawed BMD scans did not differ from the initial fresh scan (p = 0.418). Thus,
      completely thawed remains are recommended for experimental studies.

PMID- 27864951
TI  - Evaluation of the Role of Toxicological Data in Discriminating Between H2 S
      Femoral Blood Concentration Secondary to Lethal poisoning and Endogenous H2 S
      Putrefactive Production.
AB  - Hydrogen sulfide is a colorless gas and has a strong odor of rotten eggs. It is
      absorbed by the upper respiratory tract mucosa, and it causes histotoxic
      hypoxemia and respiratory depression by exerting an inhibitory effect on
      cytochrome oxidase. To evaluate the role of toxicological data in distinguishing
      between the H2 S blood concentration secondary to lethal poisoning and the
      endogenous H2 S produced during putrefaction, we compared the postmortem H2 S
      concentrations of six fatal H2 S poisoning cases (8.7-28.6 mg/L) with the
      postmortem concentrations of endogenous H2 S of 12 subjects who died from other
      causes (traffic-related deaths) (2.2-32.7 mg/L). These results will be of
      interest to the forensic community as it underlines the importance of considering
      circumstantial evidence along with the toxicological and pathological findings in
      the identification of H2 S lethal poisoning.

PMID- 27864952
TI  - Sudden Infant and Early Childhood Death and Sinus of Valsalva Pseudoaneurysms.
AB  - Two cases of occult pseudoaneurysms of the sinus of Valsalva (SoV) are reported
      to demonstrate different etiologies and lethal mechanisms. A previously well 9
      month-old boy who suffered an unexpected fatal cardiorespiratory arrest was found
      at autopsy to have a ruptured pseudoaneurysm of the left SoV resulting in lethal
      hemopericardium. A 13.5-month-old boy died soon after presenting with a 24-h
      history of poor feeding and reduced urine output. At autopsy, destruction of the
      noncoronary cusp of the aortic valve by bacterial endocarditis was found with
      extension of the inflammation into a pseudoaneurysm of the SoV with surrounding
      abscess formation involving the atrioventricular node. Death was most likely due
      to an arrhythmia. Pseudoaneurysms of the SoV are exceedingly rare but may result
      in sudden/unexpected death in infancy and early childhood from rupture or
      involvement of the conduction system or myocardium. Detailed cardiac examination
      is essential in all unexpected deaths in early life.

PMID- 27864953
TI  - Deaths in Unlicensed Alcohol Rehabilitation Facilities<sup/>.
AB  - Non-English-speaking people do not always seek medical care through established
      institutions. This paper reports a series of deaths in unlicensed alcohol
      rehabilitation facilities serving Spanish-speaking men. These facilities are
      informal groups of alcohol abusing men who live together. New members receive
      various treatments, including administration of ethanol or isopropanol,
      restraint, and seclusion. We reviewed 42 deaths in unlicensed alcohol
      rehabilitation facilities in Los Angeles County during the years 2003-2014. Data
      gathered included age, length of time spent in the facility, blood alcohol and
      drugs at autopsy, and cause and manner of death. Causes of death included acute
      alcohol poisoning, alcohol withdrawal, and a variety of other causes. Three cases
      were considered homicides from restraint asphyxia. The Department of Medical
      Examiner-Coroner has worked with the police, district attorney, and State
      Department of Health Services to try to prevent additional deaths in unlicensed
      alcohol rehabilitation facilities. Nevertheless, prevention has been difficult.

PMID- 27864954
TI  - Prevalence of comorbidity and associated risk factors in adults with atopic
      dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common chronic skin disorder, which may
      persist into adulthood; however, the prevalence of comorbidities in patients with
      AD is not well characterized. AD is considered a systemic disorder like
      psoriasis, which has raised a need for data on the comorbidity profile of
      patients with AD, to assess the potential risks, benefits, and complications in
      management of patients with AD. We described the occurrence of medical and
      psychiatric comorbidities and associated risk factors in adults with AD compared
      with psoriasis and the general population. METHODS: All Danish individuals aged
      >=18 years with a hospital (inpatient or ambulatory) diagnosis of AD or psoriasis
      during the study period (January 1, 1995-December 31, 2012) were linked in
      administrative registers. RESULTS: Overall, prevalence of smoking and alcohol
      abuse was higher among patients with AD than the general population, but lower
      than psoriasis patients. Similarly, patients with AD had more risk factors and
      higher prevalence of comorbidity than the general population, but lower
      prevalence and reduced risk compared to psoriasis patients, except for use of
      anxiolytics, which was higher in severe AD. Prevalence of diabetes was lower in
      AD than psoriasis patients as well as general population controls. CONCLUSIONS:
      Despite an increased risk of various medical and psychiatric comorbidities
      compared to general population controls, adult patients with AD had markedly
      lower prevalence of cardiovascular disease than psoriasis patients. However,
      prevalence of psychiatric comorbidity and tobacco smoking was alarmingly high in
      severe patients with AD, which might be target for intervention in patient
      management.

PMID- 27864957
TI  - Applications of the fast-slow continuum and reproductive strategy framework of
      plant life histories.
AB  - Contents 1618 I. 1618 II. 1619 III. 1620 IV. 1623 1623 References 1624 SUMMARY:
      Understanding the forces that shape the great amount of variation in plant
      longevity, reproductive output and growth rate is fundamental to effective
      predictions of viability, invasions and evolutionary pressures. Here, I extend
      the recently introduced 'fast-slow continuum and reproductive strategy' framework
      to quantify the variation in plant life history strategies world-wide. I use high
      resolution demographic information from 625 plant species and show that this
      framework predicts not only key demographic properties, such as population growth
      rate and demographic resilience, but also has important connections to the leaf
      economics spectrum, biogeographical characteristics, evolutionary biology and
      conservation biology. This framework may allow plant biologists to unlock
      powerful global plant predictions from a handful of open-access field
      measurements.

PMID- 27864955
TI  - Not only age but also tactile perception influences the preference for cosmetic
      creams applied to the forearm.
AB  - OBJECTIVE: We aimed to examine whether and how age as well as tactile sensitivity
      and perception had an impact on how women liked richer and lighter creams.
      Furthermore, the question arose if age and tactile perception had an influence on
      the ability to distinguish between the creams and how the ability to distinguish
      between creams influenced the liking of these creams. METHODS: A total of 299
      female participants were invited to rate how much they liked four different
      cosmetic creams applied to their forearms. The creams were based on the same base
      formula but differed with respect to the texture. In order to arouse the
      impression of more lightness (quasi-light) or more richness (quasi-rich),
      polyethylene particles of different sizes were added to the base formula. First
      of all, the participants were tested for their tactile sensitivity and
      perception. Tactile sensitivity was tested by Von Frey filaments, tactile spatial
      perception by the tactile Landolt ring test and the ability to discriminate
      surface structures by a sandpaper test. Furthermore, the participants rated the
      creams with respect to the acceptance, the subjective skin feeling after
      application and performed paired-comparison tests. Analyses of variance and
      regression analyses were applied to the data. RESULTS: In general, participants
      liked quasi-rich creams less than quasi-light creams. However, older women
      compared to younger women and women with lower tactile performance in comparison
      with women with higher tactile performance revealed a weaker influence of cream
      type-specific acceptance ratings. Further results revealed that young
      participants perceived the quasi-light creams (with particles of ~50 MUm
      diameter) as soft and quasi-rich creams (with particles of ~100 MUm and ~165 MUm
      diameter), as coarse. In contrast, this subjective skin feeling after application
      in participants at age 50 and older did not differ much. CONCLUSION: Age and
      tactile perceptual abilities have additive effects on the acceptance of creams
      with different textures when applied to the forearm.

PMID- 27864956
TI  - An Examination of the Transition of Fracture Characteristics in Long Bones from
      Fresh to Dry in Central Florida: Evaluating the Timing of Injury.
AB  - It is important to conduct timing of injury research analyzing fracture
      characteristics at known postmortem intervals (PMI) because bone can retain fresh
      characteristics throughout the PMI. Defleshed pig (Sus scrofa) long bones were
      fractured weekly in two environments (full sun and shade) over 14 weeks in
      Central Florida and fracture characteristics were categorized (N = 136) for
      analysis. Results of analysis of variance (ANOVA) using time in weeks (PMI) as a
      dependent variable indicate significant relationships between PMI and Fracture
      Angle (p < 0.001), Fracture Surface (p < 0.001), and Fracture Outline (p <
      0.001). Fracture characteristics associated with perimortem trauma (smooth
      Fracture Surfaces and curved or V-shaped Fracture Outlines) were commonly
      observed. Analysis of fracture characteristics for each environment demonstrated
      similar patterns. Overall, the loss of only fresh fracture characteristics for
      each bone was noted earlier in the PMI for the Central Florida region than
      previously reported.

PMID- 27864958
TI  - Patient Profiles of Criminal Behavior in the Context of Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) can lead to significant post-traumatic disturbances
      in mood and behavior, with the frontal lobes playing a key role in emotional and
      behavioral regulation. Injury to the frontal lobe can result in disinhibition and
      aggression which can result in police intervention and/or incarceration. We
      highlight four adult cases with a history of severe TBI with frontal lobe
      injuries and the presence of post-TBI criminal behaviors. There is evidence to
      support an anatomical basis for aggressive behaviors, yet there are other risk
      factors to be considered. Behaviors must be investigated thoroughly by obtaining
      adequate pre- and post-TBI psychiatric and psychosocial histories. By having a
      comprehensive understanding of aggression while appreciating the complex
      relationship between TBI, aggression, and premorbid risk factors, clinicians can
      more adequately treat patients with TBI, with the aim of potentially preventing
      criminal behaviors and recidivism.

PMID- 27864959
TI  - Measuring the Frequency Occurrence of Handwriting and Handprinting
      Characteristics<sup/>.
AB  - The premise of this study was to take a valid population sampling of handwriting
      and handprinting and assess how many times each of the predetermined
      characteristic is found in the samples. Approximately 1500 handwriting specimens
      were collected from across the United States and pared to obtain a representative
      sample of the U.S. adult population according to selected demographics based on
      age, sex, ethnicity, handedness, education level, and location of lower-grade
      school education. This study has been able to support a quantitative assessment
      of extrinsic and intrinsic effects in handwriting and handprinting for the six
      subgroups. Additional results include analyses of the interdependence of
      characteristics. This study found that 98.55% of handprinted characteristics and
      97.39% of cursive characteristics had an independence correlation of under 0.2.
      The conclusions support use of the product rule in general, but with noted
      caveats. Finally, this study provides frequency occurrence proportions for 776
      handwriting and handprinting characteristics.

PMID- 27864960
TI  - The Interplay Between Diabetes and Pancreatitis: Two Case Reports of Sudden,
      Natural Deaths and a Review of the Literature.
AB  - Diabetes mellitus (DM) is a common disease involving insulin resistance or
      deficit that, when left unchecked, may cause severe hyperglycemia and subsequent
      end-organ damage. Acute pancreatitis (AP) is inflammation of the pancreas that
      can lead to significant morbidity and mortality. AP and DM both account for a
      significant amount of sudden deaths, and rarely both disease processes may be
      present in the same decedent, causing some difficulty in wording the cause of
      death statement. Although much research has been directed at studying the causes
      and risk factors for AP and DM, there is a complex interplay between these
      diseases that is not fully understood. This study presents two autopsy cases of
      sudden, natural deaths that illustrate this interplay, along with a review of the
      literature. An algorithm for differentiating AP and DM is then discussed in the
      context of the presented cases as a proposed aid for forensic pathologists in the
      certification of such deaths.

PMID- 27864961
TI  - Sexual Dimorphism of Maxillary Sinus Dimensions Using Cone-Beam Computed
      Tomography.
AB  - Sex determination of unknown persons plays an important role in forensic
      medicine. Cone-beam computed tomography (CBCT) is an excellent imaging modality
      for accurate measurement of maxillary sinus dimensions. This study aimed to
      evaluate whether maxillary sinus measurements on CBCT scans can be applied for
      sex determination. The width, length, and height of maxillary sinuses in CBCT
      images of 100 patients (50 males and 50 females) were measured. Student's t-test
      and discriminant function analysis were used to compare differences in the
      measured parameters between males and females. The correct predictive accuracy
      rate of sex determination was 78% in females and 74% in males with overall
      accuracy of 76%. Based on discriminant analysis, the most pronounced variable in
      differentiation of sex groups was maxillary sinus height. This study suggests
      that maxillary sinus measurements can be valuable for sex determination in
      forensic investigation, especially for cases in which other traditional methods
      are not applicable.

PMID- 27864962
TI  - The Aquilegia JAGGED homolog promotes proliferation of adaxial cell types in both
      leaves and stems.
AB  - In order to explore the functional conservation of JAGGED, a key gene involved in
      the sculpting of lateral organs in several model species, we identified its
      ortholog AqJAG in the lower eudicot species Aquilegia coerulea. We analyzed the
      expression patterns of AqJAG in various tissues and developmental stages, and
      used RNAi-based methods to generate knockdown phenotypes of AqJAG. AqJAG was
      strongly expressed in shoot apices, floral meristems, lateral root primordia and
      all lateral organ primordia. Silencing of AqJAG revealed a wide range of defects
      in the developing stems, leaves and flowers; strongest phenotypes include severe
      reduction of leaflet laminae due to a decrease in cell size and number, change of
      adaxial cell identity, outgrowth of laminar-like tissue on the inflorescence
      stem, and early arrest of floral meristems and floral organ primordia. Our
      results indicate that AqJAG plays a critical role in controlling primordia
      initiation and distal growth of floral organs, and laminar development of
      leaflets. Most strikingly, we demonstrated that AqJAG disproportionally controls
      the behavior of cells with adaxial identity in vegetative tissues, providing
      evidence of how cell proliferation is controlled in an identity-specific manner.

PMID- 27864963
TI  - Chronic Alcohol Abuse Leads to Low Bone Mass with No General Loss of Bone
      Structure or Bone Mechanical Strength<sup/>.
AB  - : Chronic alcohol abuse (CAA) has deleterious effects on skeletal health. This
      study examined the impact of CAA on bone with regard to bone density, structure,
      and strength. Bone specimens from 42 individuals with CAA and 42 individuals
      without alcohol abuse were obtained at autopsy. Dual-energy X-ray absorptiometry
      (DEXA), compression testing, ashing, and bone histomorphometry were performed.
      Individuals with CAA had significantly lower bone mineral density (BMD) in the
      femoral neck and significantly lower bone volume demonstrated by thinner
      trabeculae, decreased extent of osteoid surfaces, and lower mean wall thickness
      of trabecular osteons compared to individuals without alcohol abuse. No
      significant difference was found for bone strength and structure. CONCLUSION: CAA
      leads to low bone mass due to a decrease in bone formation but with no
      destruction of bone architecture nor a decrease in bone strength. It is
      questionable whether this per se increases fracture risk.

PMID- 27864964
TI  - No evidence that boron influences tree species distributions in lowland tropical
      forests of Panama.
AB  - It was recently proposed that boron might be the most important nutrient
      structuring tree species distributions in tropical forests. Here we combine
      observational and experimental studies to test this hypothesis for lowland
      tropical forests of Panama. Plant-available boron is uniformly low in tropical
      forest soils of Panama and is not significantly associated with any of the > 500
      species in a regional network of forest dynamics plots. Experimental manipulation
      of boron supply to seedlings of three tropical tree species revealed no evidence
      of boron deficiency or toxicity at concentrations likely to occur in tropical
      forest soils. Foliar boron did not correlate with soil boron along a local scale
      gradient of boron availability. Fifteen years of boron addition to a tropical
      forest increased plant-available boron by 70% but did not significantly change
      tree productivity or boron concentrations in live leaves, wood or leaf litter.
      The annual input of boron in rainfall accounts for a considerable proportion of
      the boron in annual litterfall and is similar to the pool of plant-available
      boron in the soil, and is therefore sufficient to preclude boron deficiency. We
      conclude that boron does not influence tree species distributions in Panama and
      presumably elsewhere in the lowland tropics.

PMID- 27864965
TI  - Attempted Drug-facilitated Sexual Assault-Xylazine Intoxication in a Child.
AB  - There are only a few cases of drug-facilitated sexual assaults on children
      reported in the literature so far. Here, a case of a four-year-old boy is
      presented. He was unconscious, and the accompanying adults reported that the
      child had been at a playground on his own. Returning home, he complained of
      having been stung and collapsed immediately. Urine and serum samples of the child
      were investigated. In the toxicological analysis, xylazine, a sedative and muscle
      relaxant used in animals, was detected. Subsequent quantification by GC/MS after
      solid-phase extraction revealed 0.053 mg/L xylazine in serum and approximately
      0.63 mg/L in urine. Furthermore, the child was examined by a forensic medical
      specialist. Police investigations revealed that the godfather, who had been
      previously accused of sexual abuse of children, had injected the child with the
      drug, possibly in preparation for a shared bath.

PMID- 27864966
TI  - Interactive effects of water limitation and elevated temperature on the
      physiology, development and fitness of diverse accessions of Brachypodium
      distachyon.
AB  - An enduring question in plant physiology and evolution is how single genotypes of
      plants optimize performance in diverse, often highly variable, environments. We
      grew 35 natural accessions of the grass Brachypodium distachyon in four
      environments in the glasshouse, contrasting soil water deficit, elevated
      temperature and their interaction. We modeled treatment, genotype and interactive
      effects on leaf-level and whole-plant traits, including fecundity. We also
      assessed the relationship between glasshouse-measured traits and parameters
      related to climate at the place of origin. We found abundant genetic variation in
      both constitutive and induced traits related to plant-water relations. Most
      traits showed strong interaction between temperature and water availability, and
      we observed genotype-by-environment interaction for several traits. Notably, leaf
      free proline abundance showed a strong effect of genotype * temperature * water.
      We found strong associations between phenology, biomass and water use efficiency
      (WUE) with parameters describing climate of origin. Plants respond to multiple
      stressors in ways not directly predictable from single stressors, underscoring
      the complex and trait-specific mechanisms of environmental response. Climate
      trait correlations support a role for WUE and phenology in local adaptation to
      climate in B. distachyon.

PMID- 27864967
TI  - Chemokine receptors in allergic diseases.
AB  - Under homeostatic conditions, as well as in various diseases, leukocyte migration
      is a crucial issue for the immune system that is mainly organized through the
      activation of bone marrow-derived cells in various tissues. Immune cell
      trafficking is orchestrated by a family of small proteins called chemokines.
      Leukocytes express cell-surface receptors that bind to chemokines and trigger
      transendothelial migration. Most allergic diseases, such as asthma, rhinitis,
      food allergies, and atopic dermatitis, are generally classified by the tissue
      rather than the type of inflammation, making the chemokine/chemokine receptor
      system a key point of the immune response. Moreover, because small antagonists
      can easily block such receptors, various molecules have been developed to
      suppress the recruitment of immune cells during allergic reactions, representing
      potential new drugs for allergies. We review the chemokines and chemokine
      receptors that are important in asthma, food allergies, and atopic dermatitis and
      their respectively developed antagonists.

PMID- 27864968
TI  - Taphonomic Effects of Mechanical Plowing on Buried Juvenile-Sized Remains.
AB  - Agricultural activity is a worldwide taphonomic process and can present unique
      challenges in the recovery of buried remains. Previous research has been mostly
      within the realm of site formation processes of archeological sites utilizing
      only surface material. This research expands upon the previous research by
      incorporating the distribution of subsurface material by the use of archeological
      excavation techniques. An experiment was conducted utilizing juvenile pig (Sus
      scrofa) skeletons buried in relative anatomical position at two different depths
      (15 cm below the surface [cmbs] and 22 cmbs). The burials were then subjected to
      different intervals of mechanical plowing: one, three, five, seven, or 10 plow
      passes. The skeletal material was recovered using pedestrian survey followed by
      hand excavation and screening of all sediments. This research shows that there is
      a significant relationship between the degree of plowing and the distance
      skeletal material is distributed and the percentage of material recovered
      undamaged.

PMID- 27864969
TI  - Transformation of the cucurbit powdery mildew pathogen Podosphaera xanthii by
      Agrobacterium tumefaciens.
AB  - The obligate biotrophic fungal pathogen Podosphaera xanthii is the main causal
      agent of powdery mildew in cucurbit crops all over the world. A major limitation
      of molecular studies of powdery mildew fungi (Erysiphales) is their genetic
      intractability. In this work, we describe a robust method based on the
      promiscuous transformation ability of Agrobacterium tumefaciens for reliable
      transformation of P. xanthii. The A. tumefaciens-mediated transformation (ATMT)
      system yielded transformants of P. xanthii with diverse transferred DNA (T-DNA)
      constructs. Analysis of the resultant transformants showed the random integration
      of T-DNA into the P. xanthii genome. The integrations were maintained in
      successive generations in the presence of selection pressure. Transformation was
      found to be transient, because in the absence of selection agent, the introduced
      genetic markers were lost due to excision of T-DNA from the genome. The ATMT
      system represents a potent tool for genetic manipulation of P. xanthii and will
      likely be useful for studying other biotrophic fungi. We hope that this method
      will contribute to the development of detailed molecular studies of the intimate
      interaction established between powdery mildew fungi and their host plants.

PMID- 27864970
TI  - Color Stability of Dental Restorative Materials Submitted to Heat Sources, for
      Forensic Purposes.
AB  - During postmortem examination of the dental arches of carbonized victims, dental
      restorative materials may be found. The aim of this study was to evaluate the
      effect of heat source action on the color stability of composite resin (CR) and
      glass ionomer cement (GIC) restorations, to discriminate between them and compare
      with antemortem dental data. Sixty bovine teeth (30 CR and 30 GIC) were prepared
      (6 * 6 * 2 mm) and separated into groups (n = 10). The color readouts were taken
      by spectrophotometer, before and after heat action (100 degrees C, 200 degrees C,
      300 degrees C), in an oven for 15 min. There were color alterations for all
      coordinates (DeltaE, DeltaL*, Deltaa* eDeltab*) for both materials. GIC presented
      greater change. The authors concluded that it is possible to distinguish between
      the materials by the color changes analyzed by instrumental method, helping
      victim identification.

PMID- 27864971
TI  - Proximal End Root Morphology Characteristics in Antemortem Anagen Head Hairs.
AB  - The proximal end morphology of antemortem anagen head hair was compared with the
      characteristics documented to occur in postmortem hairs. Antemortem anagen and
      telogen head hairs (N = 967) were recovered following exposure to seven
      environments. Root morphology characteristics consistent with those reported in
      postmortem hairs were observed in 66 (14%) hairs exposed to a water, normal
      saline, outdoor soil, or indoor shower environment. Thirty-three anagen hairs
      (7%) exhibited a root band at the proximal end. The mean distance from the root
      tip to the onset of the root band ranged from 0.23 to 0.7 mm, depending on the
      environment. The mean distance from the root tip to the onset of the root band
      was 0.46 mm, with a mean band length of 0.44 mm. The results illustrate the need
      to better characterize postmortem banding through quantitative measurements,
      including the range for root tip to band distance and the overall band length.

PMID- 27864972
TI  - A Morphological and Morphometric Study of Bite Marks Caused by Mice (Mus
      Musculus) on Different Baits for Forensic Purposes.
AB  - In animal bites, the dental attributes can be fundamental in identifying the
      marks made by various species on different matrices. Although rodent bite marks
      have been studied in the context of postmortem interference, little research has
      used different baits to analyze these marks linking not only specific behavior
      patterns but also the possibility of structural damage. Twenty mice (Mus
      musculus) were exposed to different baits to study their bite marks in a
      controlled model. The known pattern of parallel and multiple grooves has been
      seen in all baits, but polyvinyl chloride and fiber-optic cable were
      significantly different between each other and the other baits. Some baits showed
      patterns of anchorage of the upper incisors and space between the lower incisors
      when gnawing. This technical note represents a novel model of analysis where
      veterinarians and/or dentists may be asked to give an opinion on alleged animal
      bite marks.

PMID- 27864974
TI  - NLRP3 inflammasome may regulate inflammatory response of human periodontal
      ligament fibroblasts in an apoptosis-associated speck-like protein containing a
      CARD (ASC)-dependent manner.
AB  - AIM: To explore the role of NLRP3 (NACHT [nucleotide-binding oligomerization],
      LRR [leucine-rich repeat] and PYD [pyrin domain] domains-containing protein 3)
      inflammasome in the inflammatory response of human periodontal ligament
      fibroblasts (HPDLFs). METHODOLOGY: The expression of NLRP3 and apoptosis
      associated speck-like protein containing a CARD (ASC) in inflammatory periapical
      tissues and HPDLFs was examined by immunohistochemical and immunofluorescent
      staining. HPDLFs were stimulated with muramyl dipeptide (MDP) and
      lipopolysaccharide (LPS) from E. coli with or without the silencing of ASC. The
      expression of NLRP3, ASC and caspase-1 was examined using quantitative real-time
      polymerase chain reaction. The secretion of proinflammatory cytokines, including
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor
      alpha (TNF-alpha) was measured in the cell supernatant with an enzyme-linked
      immunosorbent assay. Data were statistically analysed using independent sample t
      tests. RESULTS: Immunohistochemistry and immunocytochemistry staining revealed
      that NLRP3 and ASC were expressed in HPDLFs and inflammatory periapical tissues.
      MDP and LPS promoted the expression of NLRP3, ASC and caspase-1 in HPDLFs (P <
      0.05). The secretion of proinflammatory cytokines was also increased with MDP and
      LPS stimulation (P < 0.05). After silencing ASC, the secretion of IL-1beta
      induced by MDP and LPS was significantly attenuated (P < 0.05). CONCLUSION: In
      HPDLFs, MDP and LPS activated NLRP3 inflammasome and induced IL-1beta secretion.
      ASC plays an important role in this inflammatory response.

PMID- 27864973
TI  - The evolution of symbiont preference traits in the model legume Medicago
      truncatula.
AB  - Many hosts preferentially associate with or reward better symbionts, but how
      these symbiont preference traits evolve is an open question. Legumes often form
      more nodules with or provide more resources to rhizobia that fix more nitrogen
      (N), but they also acquire N from soil via root foraging. It is unclear whether
      root responses to abiotically and symbiotically derived N evolve independently.
      Here, we measured root foraging and both preferential allocation of root
      resources to and preferential association with an effective vs an ineffective N
      fixing Ensifer meliloti strain in 35 inbred lines of the model legume Medicago
      truncatula. We found that M. truncatula is an efficient root forager and forms
      more nodules with the effective rhizobium; root biomass increases with the number
      of effective, but not ineffective, nodules, indicating preferential allocation to
      roots harbouring effective rhizobia; root foraging is not genetically correlated
      with either preferential allocation or association; and selection favours plant
      genotypes that form more effective nodules. Root foraging and symbiont preference
      traits appear to be genetically uncoupled in M. truncatula. Rather than evolving
      to exclude ineffective partners, our results suggest that preference traits
      probably evolve to take better advantage of effective symbionts.

PMID- 27864975
TI  - On the importance of composite protein multiple ligand interactions in protein
      pockets.
AB  - Conventional small molecule drug-discovery approaches target protein pockets.
      However, the limited number of geometrically distinct pockets leads to widespread
      promiscuity and deleterious side-effects. Here, the idea of COmposite protein
      LIGands (COLIG) that interact with each other as well as the protein within a
      single ligand binding pocket is examined. As a practical illustration,
      experimental evidence that E. coli Dihydrofolate reductase inhibitors are COLIGs
      is presented. Then, analysis of a non-redundant set of all holo PDB structures
      indicates that almost 47-76% of proteins (based on different sequence identity
      thresholds) can simultaneously bind multiple, interacting ligands in the same
      pocket. Moreover, most ligands that are either Singletons and COLIGs bind at the
      bottom of ligand binding pocket and occupy 30% and 43% of the volume of the
      bottom of the pocket. This suggests the use of COLIGs as a potential new class of
      small molecule drugs. (c) 2016 Wiley Periodicals, Inc.

PMID- 27864976
TI  - An effective diagnostic strategy for accurate detection of RhD variants including
      Asian DEL type in apparently RhD-negative blood donors in Korea.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to provide an effective
      RHD genotyping strategy for the East Asian blood donors. MATERIAL AND METHODS:
      RhD phenotyping, weak D testing and RhCE phenotyping were performed on 110
      samples from members of the RhD-negative club, private organization composed of
      RhD-negative blood donors, in the GwangJu-Chonnam region of Korea. The RHD
      promoter, intron 4, and exons 7 and 10 were analysed by real-time PCR. Two
      nucleotide changes (c.1227 G>A, and c.1222 T>C) in exon 9 were analysed by
      sequencing. RESULTS: Of 110 RhD-negative club members, 79 (71.8%) showed complete
      deletion of the RHD gene, 10 (9.1%) showed results consistent with RHD-CE-D
      hybrid, and 21 (19.1%) showed amplification of RHD promoter, intron 4, and exons
      7 and 10. Of the latter group, 16 (14.5%) were in the DEL blood group including
      c.1227 G>A (N = 14) and c.1222 T>C (N = 2), 2 (1.8%) were weak D, 1(0.9%) was
      partial D, and 2 (1.8%) were undetermined. The RhD-negative phenotype samples
      consisted of 58 C-E-c+e+, 19 C-E+c+e+, 3 C-E+c+e-, 21 C+E-c+e-, 6 C+E-c+e+ and 3
      C+E-c-e + . Notably, all 58 samples with the C-E-c+e+ phenotype were revealed to
      have complete deletion of the RHD gene. The C-E-c+e+ phenotype showed 100%
      positive predictive value for detecting D-negative cases. CONCLUSIONS: RHD
      genotyping is not required in half of D-negative cases. We suggest here an
      effective RHD genotyping strategy for accurate detection of RhD variants in
      apparently RhD-negative blood donors in East Asia.

PMID- 27864978
TI  - Reduction of biological response modifiers in the supernatant of washed
      paediatric red blood cells.
AB  - BACKGROUND: Washing of red blood cells (RBC) can reduce unwanted biological
      response modifiers (BRMs) that can mediate transfusion complications in infants.
      The aim of this study was to examine the in vitro quality and the changes in BRMs
      following washing in paediatric RBC units. MATERIALS AND METHODS: A pool and
      split design was used to prepare RBC (either 1 or 4 days old; n = 26 pairs). One
      unit was washed with 0.9% saline by centrifugation and then resuspended in SAG-M,
      while the other remained unwashed. Each RBC unit was divided to produce four
      units of paediatric-sized components. Samples were taken after 3 h and
      subsequently on days 1, 2, 7 and 14 post-wash. RESULTS: Washing of RBC resulted
      in some red cell loss, with a minor increase in haemolysis. Washing effectively
      reduced supernatant potassium and IgA, as well as cytokines and complement
      proteins. RBC microparticles were significantly reduced in RBC washed at 1, but
      not 4 days post-collection. Incubation with supernatant from unwashed but not
      washed RBC led to endothelial cell activation, with increased cell surface
      expression of CD62E (E-selectin) and CD106 (VCAM). CONCLUSION: Although washing
      affected some aspects of the in vitro quality of RBC, it effectively reduced the
      concentration and activity of BRMs in the supernatant of RBC. Such a reduction
      may be clinically beneficial in selected patient groups.

PMID- 27864980
TI  - Erratum.

PMID- 27864979
TI  - Modelling gas exchange during platelet storage without agitation.
AB  - The aim of this study was to create a model of oxygen distribution within
      platelet storage bags to evaluate implications of reduced agitation approaches.
      Based on our model, platelet concentration and surface area most affect internal
      partial pressure of oxygen, while temperature modifications have least effect,
      indicating primary potential approaches for optimization of platelet storage with
      reduced or absent agitation.

PMID- 27864981
TI  - Interventions for nurses' well-being at work: a quantitative systematic review.
AB  - AIM: To gather, assess and synthesize current research knowledge on the
      interventions aiming to improve nurses' well-being at work. BACKGROUND: Previous
      reviews describe health care professionals' well-being at work from the
      perspective of burnout. Research on the interventions for and their effectiveness
      on nurses' well-being at work is sporadic. DESIGN: A quantitative systematic
      review based on the procedure of the Centre for Reviews and Dissemination.
      METHODS: CINAHL, Cochrane, EBSCO, PubMed, PsycInfo, Scopus databases were sought
      from 2009-March 2015. The final data consisted of eight studies described in 10
      articles. The study design was RCT in three studies, CBA in three and ITS in two
      studies. The studies were assessed with the Cochrane risk of bias tool. Data were
      summarised narratively and displayed in a harvest plot. RESULTS: Two of the six
      interventions were person-directed, two combined person- and organisation
      directed and two organisation-directed interventions. Half of them were mainly
      targeted at stress management while the others aimed at improving interaction
      with colleagues, work methods and conditions or at supervision of professional
      skills. CONCLUSIONS: There was a lot variation in the conceptual bases and the
      use of evaluation measurements in the studies and the interventions were carried
      out in a heterogeneous way. Moderate evidence was found to support the use of
      interventions among nurses employed at in-patient and out-patient units in four
      out of the six interventions. The review pointed out a need for research on
      standardised interventions on nurses' well-being at work and their effectiveness
      with long-term follow-ups.

PMID- 27864982
TI  - Unusual findings in common peripheral ossifying fibromas: transepithelial
      elimination and epithelial inclusion.

PMID- 27864983
TI  - Diagnosis of unilateral trapezius muscle palsy: 54 Cases.
AB  - INTRODUCTION: We assessed medical and surgical causes of unilateral trapezius
      muscle (TM) palsy and/or wasting. METHODS: Clinical and electrodiagnostic data
      were collected in 54 patients with TM impairment over 21 years. RESULTS: In
      total, 35 cases had a medical origin: neuralgic amyotrophy (NA, n = 22),
      idiopathic unilateral TM palsy (n = 5), regional neck radiotherapy for different
      conditions (n = 2), facioscapulohumeral dystrophy (FSH) (n = 4), abnormal loop of
      the jugular vein (n = 1), or basilar impression (n = 1). Other etiologies were
      neck surgery (n = 16), cervicofacial lift (n = 2), or trauma (n = 1).
      CONCLUSIONS: There were 5 main diagnostic findings in unilateral TM palsy: (1)
      dynamic examination of the scapula provides a new clinical sign; (2) NA is the
      most frequent medical cause; (3) in medical cases, partial preservation of the
      upper TM can offer good recovery; (4) FSH must be considered, especially in young
      patients; and (5) minor neck surgery can lead to severe TM palsy. Muscle Nerve
      56: 215-223, 2017.

PMID- 27864984
TI  - Simultaneous biodegradation of three mononitrophenol isomers by a tailor-made
      microbial consortium immobilized in sequential batch reactors.
AB  - : The ortho-nitrophenol (ONP)-utilizing Alcaligenes sp. strain NyZ215, meta
      nitrophenol (MNP)-utilizing Cupriavidus necator JMP134 and para-nitrophenol (PNP)
      utilizing Pseudomonas sp. strain WBC-3 were assembled as a consortium to degrade
      three nitrophenol isomers in sequential batch reactors. Pilot test was conducted
      in flasks to demonstrate that a mixture of three mononitrophenols at 0.5 mol l-1
      each could be mineralized by this microbial consortium within 84 h.
      Interestingly, neither ONP nor MNP was degraded until PNP was almost consumed by
      strain WBC-3. By immobilizing this consortium into polyurethane cubes, all three
      mononitrophenols were continuously degraded in lab-scale sequential reactors for
      six batch cycles over 18 days. Total concentrations of ONP, MMP and PNP that were
      degraded were 2.8, 1.5 and 2.3 mol l-1 during this time course respectively.
      Quantitative real-time PCR analysis showed that each member in the microbial
      consortium was relatively stable during the entire degradation process. This
      study provides a novel approach to treat polluted water, particularly with a
      mixture of co-existing isomers. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Nitroaromatic compounds are readily spread in the environment and pose great
      potential toxicity concerns. Here, we report the simultaneous degradation of
      three isomers of mononitrophenol in a single system by employing a consortium of
      three bacteria, both in flasks and lab-scale sequential batch reactors. The
      results demonstrate that simultaneous biodegradation of three mononitrophenol
      isomers can be achieved by a tailor-made microbial consortium immobilized in
      sequential batch reactors, providing a pilot study for a novel approach for the
      bioremediation of mixed pollutants, especially isomers present in wastewater.

PMID- 27864985
TI  - Telomeric repeat-containing RNA (TERRA) related to polycystic ovary syndrome
      (PCOS).
AB  - CONTEXT: Telomeric repeat-containing RNA (TERRA) participates in the regulation
      of telomere length, and leucocyte telomere length (LTL) plays an important role
      in the pathophysiology of polycystic ovary syndrome (PCOS), but little is known
      about the role of TERRA in PCOS. OBJECTIVE: To evaluate the role of TERRA and
      peripheral blood LTL in PCOS. DESIGN AND PARTICIPANTS: Forty women with PCOS and
      35 healthy women without PCOS were recruited. A prospective case-control study
      was performed. MEASUREMENTS: RNA fluorescence in situ hybridization (FISH) was
      used to detect TERRA expression in peripheral blood leucocyte. Quantitative PCR
      was used to measure TERRA expression and the mean LTL in the PCOS and control
      groups. We analysed the association between related clinical parameters and the
      age-adjusted ratio of the telomere repeat length (T/S ratio) or TERRA. RESULTS:
      Telomeric repeat-containing RNA was expressed in human peripheral blood
      leucocytes, and the signal was abolished after culture with RNase A. The age
      adjusted LTLs were significantly longer in the PCOS group than in the control
      group (P < 0.01). The age-adjusted TERRA level was significantly lower in the
      PCOS group than in the control group (P < 0.01). Testosterone (TTE) was related
      positively to LTL and negatively to TERRA in the PCOS group (r = 0.532, P =
      0.002; r = -0.477, P = 0.017). CONCLUSION: We found TERRA expression in human
      peripheral blood leucocytes, and LTLs were positively associated with PCOS. TERRA
      and testosterone play an important role in the LTL regulation in PCOS.

PMID- 27864986
TI  - Urinary iodine excretion (UIE) estimated by iodine/creatinine ratio from spot
      urine in Chinese school-age children.
AB  - OBJECTIVE: To assess the validity of urinary iodine excretion (UIE) estimated by
      urinary iodine/creatinine ratio (UI/Cr) from spot urines in Chinese school-age
      children. DESIGN: A cross-sectional survey was performed in which twice-repeated
      collections of 24-h urine, and spot urine samples were obtained within 1 month.
      MEASUREMENTS: Urinary iodine concentration (UIC), urinary creatinine
      concentration (UCr), urine volume (Uvol) of spot and 24-h urine samples were
      measured. Measured 24-h UIE was calculated from 24-h UIC multiplied by 24-h Uvol,
      while the estimated 24-h UIE was calculated from spot UI/Cr multiplied by 24-h
      urinary creatinine excretion (24-h UCrE). RESULTS: No significant difference was
      observed in 24-h Uvol between two repeated collections (P = 0.70), while spot
      UIC, 24-h UIC, spot UI/Cr and measured 24-h UIE were significantly different (P <
      0.05). The estimated 24-h UIE was 247 (136-431) MUg/day in the first collection,
      lower than the measured 24-h UIE of 329 (183-536) MUg/day (P < 0.001), while no
      significant difference was observed (P = 0.30) in the second sampling as the
      estimated 24-h UIE was 355 (168-624) MUg/day and the measured 24-h UIE 350 (181
      615) MUg/day. The spot UIC (r = 0.57, P < 0.001), spot UI/Cr (r = 0.63, P <
      0.001) and the estimated 24-h UIE (r = 0.83, P < 0.001) were strongly correlated
      with the measured 24-h UIE in the first collection. Likewise, in the second
      sampling, spot UIC (r = 0.60, P < 0.001), spot UI/Cr (r = 0.72, P < 0.001) and
      the estimated 24-h UIE (r = 0.89, P < 0.001) were also correlated with measured
      24-h UIE. The Bland-Altman results indicated 95% of subjects were expected to
      locate within the limits of agreement (LOA), but showed an underestimation of the
      urinary iodine excretion by the estimated 24-h UIE. In addition, moderate-to-good
      agreement was found for the estimated and measured 24-h UIE, with kappa values of
      0.55 and 0.66. CONCLUSIONS: Estimated 24-h UIE by UI/Cr ratio from spot urine
      could represent a valid and reliable alternative for measured 24-h UIE in
      estimating iodine excretion in children.

PMID- 27864987
TI  - 'Mental health day' sickness absence amongst nurses and midwives: workplace,
      workforce, psychosocial and health characteristics.
AB  - AIM: To examine the workforce, workplace, psychosocial and health characteristics
      of nurses and midwives in relation to their reported use of sickness absence
      described as 'mental health days'. BACKGROUND: The occupational stress associated
      with the nursing profession is increasingly recognized and nurse/midwifery
      absenteeism is a significant global problem. Taking a 'mental health day' as
      sickness absence is a common phenomenon in Australian health care. No previous
      studies have empirically explored the characteristics of nurses and midwives
      using such sickness absence. DESIGN: Online cross-sectional survey. METHODS:
      Survey comprising validated tools and questions on workplace and health
      characteristics was distributed to nurses and midwives in New South Wales,
      Australia, between May 2014 - February 2015. Sample characteristics were reported
      using descriptive statistics. Factors independently predictive of 'mental health
      day' reportage were determined using logistic regression. RESULTS: Fifty-four
      percentage of the n = 5041 nurse and midwife respondents took 'mental health
      days'. Those affected were significantly more likely to be at younger ages,
      working shifts with less time sitting at work; to report workplace abuse and
      plans to leave; having been admitted to hospital in previous 12 months; to be
      current smokers; to report mental health problems, accomplishing less due to
      emotional problems and current psychotropic medication use. CONCLUSION: Specific
      characteristics of nurses and midwives who report taking 'mental health day'
      sickness absence offer healthcare administrators and managers opportunities for
      early identification and intervention with workplace measures and support
      frameworks to promote well-being, health promotion and safety.

PMID- 27864988
TI  - Time to question diabetes self-management support for Arabic-speaking migrants:
      exploring a new model of care.
AB  - AIM: The objective of this study was to explore a new model for diabetes self
      management support in Arabic-speaking migrants. METHODS: Two qualitative methods
      were used: face-to-face semi-structured individual interviews and focus groups.
      Interviews were audio-taped, transcribed verbatim and coded thematically. Arabic
      speaking migrants with Type 2 diabetes were recruited from several primary,
      secondary and tertiary healthcare settings in metropolitan Melbourne, Australia.
      These settings were purposefully selected to obtain a diverse group of
      participants. Data collection continued until saturation was reached. This is the
      first study that involved members of Arabic-speaking communities in Australia in
      a formal process of consumer and public involvement to inform research design and
      recruitment in order to provide evidence for a new model of diabetes self
      management for Arabic-speaking migrants. RESULTS: No self-management support was
      offered to Arabic-speaking migrants beyond the initial diagnosis period.
      Significant knowledge gaps and skills deficits in all self-management domains
      were evident. The provision of tailored self-management support was considered
      crucial. When asked about preferred structure and delivery modalities, a strong
      preference was reported for face-to-face storytelling interactions over telephone
      or internet-based interventions. Gender-specific group education and self
      management support sessions delivered by Arabic-speaking diabetes health
      professionals, lay peers or social workers trained in diabetes self-management
      were highly regarded. CONCLUSIONS: A patient and public involvement approach
      allows genuine engagement with Arabic-speaking migrants with diabetes. There is
      urgent need for a new model for self-management support among Arabic-speaking
      migrants. Findings yielded new recommendations for diabetes health professionals
      working with these migrant communities to support behaviour change.

PMID- 27864989
TI  - The mitosis-specific marker phosphohistone-H3 (PHH3) is an independent
      prognosticator in uterine smooth muscle tumours: an outcome-based study.
AB  - AIMS: Accurate mitosis counting, which is important in the diagnosis of uterine
      smooth muscle tumours (USMTs), is often difficult and subjective. The mitosis
      specific immunohistochemical marker phosphohistone-H3 (PHH3) has been shown to be
      diagnostically useful, but its expression, in relation to outcome, has not been
      thoroughly investigated. The aim of this study is to evaluate PHH3 as a
      diagnostic and prognostic marker in USMTs. METHODS AND RESULTS: PHH3 expression
      was evaluated in 55 leiomyosarcomas (LMSs), 26 smooth muscle tumours of uncertain
      malignant potential (STUMPs), 18 leiomyomas with bizarre nuclei (LBN), and 12
      leiomyomas (LMs). Scores were expressed as counts per 10 high-power fields
      (HPFs). Median follow-up durations of patients with LMS, STUMP, LBN and LM were,
      respectively, 39, 78, 65.5 and 49.5 months. Twenty-eight patients with LMSs
      (50.9%) died, and two (7.7%) patients with STUMPs experienced recurrence. The
      median PHH3 scores for LMSs were significantly higher than those for other
      categories of tumour. A score of >=29/10 HPFs was also independently associated
      with a poor outcome. To test whether the PHH3 score could distinguish between
      benign USMTs with atypical histology and those that were clinically malignant,
      two biological groups were further delineated. Patients in group 1 (18 LBNs and
      24 STUMPs) all had an uneventful outcome, whereas patients in group 2 (two
      recurrent STUMPs and 32 LMSs) all had a recurrence or tumour-related death.
      Median PHH3 scores for the two groups were, respectively, 2/10 HPFs and 27/10
      HPFs. A PHH3 score of >=7/10 HPFs was highly associated with malignancy.
      CONCLUSION: PHH3 is useful in evaluation of the biological behaviour of USMTs,
      and may serve as a prognostic indicator for LMSs.

PMID- 27864991
TI  - The effects of life review on psycho-spiritual well-being among patients with
      life-threatening illness: a systematic review and meta-analysis.
AB  - AIM: The aim of this study was to examine the strength of evidence regarding the
      effects of life review on psycho-spiritual well-being among patients with life
      threatening illness. BACKGROUND: Life-threatening illness not only causes
      physical symptoms but also psycho-spiritual burdens. Life review has been widely
      implemented to assist people coping with these burdens. However, the
      effectiveness of life review is not clear. To date, no systematic review or meta
      analysis has been published on this topic. DESIGN AND REVIEW METHODS: A
      systematic review with meta- analysis consistent with the recommendations of the
      Cochrane Collaboration was conducted. DATA SOURCES: Database searches included
      MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL,
      PsycINFO, CNKI and VIP et al. up to April 2015. We also searched the grey
      literature, reviewed reference lists from relevant articles and book chapters and
      contacted experts. RESULTS: Nine randomized controlled trials (RCTs) and two
      controlled clinical trials (CCTs) were eligible for this systematic review and
      meta-analysis. The risk of bias for those studies were rated as moderate (n =
      11). The meta-analyses demonstrated significant standardized mean differences or
      mean differences in favour of life review compared with the control for
      depression, quality of life and self-esteem. CONCLUSION: The findings indicate
      that life review can decrease depressive symptoms, improve quality of life and
      enhance self-esteem among patients with life-threatening illnesses. Multi-centre
      studies with adequate sample size and rigorous designs are needed in future
      research.

PMID- 27864990
TI  - The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in
      Systemic Sclerosis.
AB  - Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with
      several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of
      the present multicentric study was to determine the clinical relevance of
      antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features
      of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA
      (AFA-) were collected retrospectively from medical records to enable a comparison
      between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by
      an indirect immunofluorescence technique using HEp2 cells and identified by an in
      house Western blot technique and/or an EliA test. Comparing AFA+ and AFA-
      patients, AFA+ patients were significantly younger at disease onset (36.9 versus
      42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent
      (65% versus 7.7%; P < 0.001). At diagnosis, the Rodnan skin score evaluating the
      cutaneous manifestations was higher (13.3 versus 8.7; P = 0.01) and myositis was
      also more common in the AFA+ group (31.4% versus 12.2%; P < 0.01). Patients with
      AFA+ were not associated with diffuse cutaneous SSc or with lung involvement and
      no difference in survival was observed. Antifibrillarin autoantibodies are
      associated with patients of Afro-Caribbean origin and can identify patients with
      SSc who are younger at disease onset and display a higher prevalence of myositis.

PMID- 27864992
TI  - MRI bullseye sign: An indicator of peripheral nerve constriction in parsonage
      turner syndrome.
AB  - INTRODUCTION: The role of MRI in identifying hourglass constrictions (HGCs) of
      nerves in Parsonage-Turner syndrome (PTS) is largely unknown. METHODS: Six
      patients with PTS and absent or minimal recovery underwent MRI. Surgical
      exploration was performed at identified pathologic sites. RESULTS: The time
      between symptom onset and surgery was 12.4 +/- 6.9 months; the time between MRI
      and surgery was 1.3 +/- 0.6 months. Involved nerves included suprascapular,
      axillary, radial, and median nerve anterior interosseous and pronator teres
      fascicles. Twenty-three constriction sites in 10 nerves were identified on MRI. A
      "bullseye sign" of the nerve, identified immediately proximal to 21 of 23 sites,
      manifested as peripheral signal hyperintensity and central hypointensity
      orthogonal to the long axis of the nerve. All constrictions were confirmed
      operatively. CONCLUSIONS: In PTS, a bullseye sign on MRI can accurately localize
      HGCs, a previously unreported finding. Causes of HGCs and the bullseye sign are
      unknown. Muscle Nerve 56: 99-106, 2017.

PMID- 27864993
TI  - Thyrotropin Alters T Cell Development in the Thymus in Subclinical Hypothyroidism
      Mouse Model.
AB  - Subclinical hypothyroidism (SCH) is highly prevalent in the general population
      and is associated with potential deleterious effects. Although developing T cells
      express thyroid-stimulating hormone receptor (TSH-R), the changes of T cell
      development in thymus in SCH have not been fully clarified. SCH mouse model,
      which is characterized by elevated serum TSH but similar thyroid hormone levels,
      was used to study the role of TSH in T cell development. Thymus weight of SCH
      mice increased 18% compared with controls. Importantly, the frequencies of CD4+
      and CD8+ single-positive (SP) thymocytes increased 38% and 44%, respectively. We
      demonstrated that TSH protected thymocytes from apoptosis as evidenced by a
      significant decrease of Annexin V-positive thymocytes in SCH mice. Further
      analysis showed that extracellular-regulated kinases (ERK) 1/2 in thymus were
      activated in SCH mice. With analysis of T cell receptor excision circles (TREC),
      we found that TSH increased recent thymic emigrants (RTE) in spleen tissue in SCH
      mice. Thus, these results suggest that TSH promoted T cell development and
      enhanced the thymic recent output in SCH mice, possibly by suppression of
      apoptosis of thymocytes, indicating that modification of the ERK signalling
      pathways.

PMID- 27864994
TI  - Serum sPD-L1, Upregulated in Sepsis, May Reflect Disease Severity and Clinical
      Outcomes in Septic Patients.
AB  - We aimed to find the correlation between serum sPD-L1 (soluble programmed cell
      death L-1 ligand) and sepsis. Totally 91 consecutive patients with sepsis were
      performed in a 15-bed medical intensive care unit (ICU) of the second affiliated
      hospital, Xi'an Jiaotong University in Xi'an, China, between February 2015 and
      May 2016. Healthy controls (HC) consisted of 29 healthy volunteer. Baseline
      demographic data were recorded. Blood samples were collected through an
      indwelling central venous or by peripheral venipuncture. Serum sPD-L1 and sPD-1
      levels were determined with enzyme-linked immunosorbent assay kits (Elabscience
      Biotechnology Co. Ltd, Wuhan, China). SPSS19.0 software (SPSS Inc., Chicago,
      Illinois, USA) was used for statistical analysis. Kaplan-Meier survival analysis
      and Cox regression analysis were also performed. Serum sPD-L1 levels and sPD-1
      levels were significantly increased in septic patients compared with HC (P =
      0.000). Serum sPD-L1 levels were significantly increased in non-survivors
      compared with survivors (P < 0.05), but there was no statistically difference on
      serum sPD-1 levels between non-survivors and survivors (P > 0.05). Serum sPD-L1
      levels were correlated with absolute lymphocyte (ALC), platelets and SOFA scores.
      Serum sPD-L1/sPD-1 levels were negatively correlated with ALC and platelets, and
      SOFA scores. The prognostic accuracy of the sPD-L1 level to predict 28-day
      mortality was similar to that of the APACHE-II scores and SOFA scores. Cox
      regression analysis showed that sPD-L1 was an independent prognostic factor.
      Serum sPD-L1 is upregulated in sepsis and may reflect disease severity and
      clinical outcomes in patients. Serum sPD-L1 may be an independent prognostic
      factor for sepsis.

PMID- 27864995
TI  - A systematic review: effectiveness of pediatric peripheral intravenous
      catheterization strategies.
AB  - AIM: The aim of this study was to identify interventions associated with
      peripheral intravenous catheterization first attempt success in pediatric
      inpatients and emergency department patients who require vascular access for
      therapeutic interventions. BACKGROUND: Unsuccessful peripheral intravenous
      catheterization puts children at risk for increased pain and treatment delays.
      Effective interventions to increase peripheral intravenous catheterization first
      attempt success are unclear. DESIGN: Systematic review of randomized controlled
      trials according to the Cochrane Handbook for the Systematic Review of
      Interventions. DATA SOURCES: Through November and December 2014, we searched 10
      databases including MEDLINE (OVID), EMBASE (OVID) and CINAHL (EBSCO) without date
      limits. The references of articles were also reviewed. We included full text
      reports of randomized controlled trials testing intervention first attempt
      success rates vs. standard of care. REVIEW METHODS: According to inclusion and
      exclusion criteria set a priori, data were extracted using a standardized tool.
      We assessed for risk of bias with the Cochrane Collaboration Risk of Bias Tool.
      Due to unclear reporting narrative synthesis was used to report results. RESULTS:
      Four cluster randomized control trials and ten randomized control trials
      involving 4539 participants ranging from 15.6 days to 16 years of age met our
      inclusion criteria. We excluded the four cluster trials from meta-analysis due to
      unclear reporting. Interventions did not increase first attempt success rate
      compared with standard of care. CONCLUSIONS: There was insufficient evidence to
      support the use of ultrasound, infrared light or transillumination. Interventions
      to reduce children's pain did not decrease first attempt success. Research
      examining between-clinician proficiency and persistence differences is absent.

PMID- 27864996
TI  - Skin microtopography as a measure of photoaging and risk of squamous cell
      carcinoma of the skin in a US population.
AB  - BACKGROUND: Skin microtopography as a measure of photoaging is a noninvasive
      approach to measuring chronic ultraviolet radiation exposure and reflects the
      degree of dermal elastosis in populations of European descent in the subtropics.
      Less is known about the utility of this approach in populations at different
      latitudes, and whether it relates to skin cancer risk. METHODS: A population
      based case-control study of 342 squamous cell carcinoma (SCC) cases and 331 age-
      and gender-matched controls were evaluated for histologic evidence of solar
      damage and severity of photoaging based on microtopography on a six-grade scale.
      Odds ratios (OR) for SCC associated with degree of photoaging were estimated
      using logistic regression analysis adjusted for potentially confounding factors.
      RESULTS: After adjustment for known risk factors, SCC was associated with
      increasing photoaging grade (OR = 1.7, 95% CI = 0.9-3.0 for severe photoaging; OR
      = 2.8, 95% CI = 1.6-5.0 for very severe photoaging). Associations remained among
      those with actinic keratosis (OR = 3.4, 95% CI = 0.9-12.4 for severe photoaging,
      OR = 5.7, 95% CI = 1.7-19.6 for very severe photoaging). LIMITATIONS: There was
      limited statistical power, particularly for subgroup analyses. CONCLUSION: Our
      findings provide further evidence of microtopography as an independent, objective
      indicator of risk of SCC.

PMID- 27864997
TI  - Evaluation of the efficacy of photodynamic therapy for the treatment of actinic
      cheilitis.
AB  - INTRODUCTION: Actinic cheilitis (AC) is a lip intraepithelial neoplasia, whose
      cells present alterations similar to those presented by invasive squamous cell
      carcinomas (SCCs). OBJECTIVE: To conduct clinical and laboratory evaluation by
      histopathology and immunohistochemistry of the efficacy of actinic cheilitis
      treatment using photodynamic therapy (PDT) with methyl aminolevulinate (MAL) and
      noncoherent red light. MATERIALS AND METHODS: Patients with actinic cheilitis
      detected by histopathological examination were submitted to two sessions of
      photodynamic therapy with a two-week interval between them. They were examined
      immediately after the sessions, four, six, and twelve weeks after beginning
      treatment when a new biopsy was carried out. Clinical histopathological and
      immunohistochemical parameters were evaluated before and after treatment.
      RESULTS: Of the 23 patients who underwent biopsy, 16 completed two photodynamic
      therapy sessions and the material of one patient was insufficient for
      immunohistochemistry. Complete clinical response was achieved in 62.5% (10 of 16
      patients) and 37.5% still remained with clinical evidence of AC. In spite of
      this, no case of cure by histopathological analysis was found. There was no
      significant statistical change among the values of Ki-67, survivin, and p53
      observed before and after treatment. CONCLUSION: Photodynamic therapy, as carried
      out in this trial, was not an efficacious therapeutic option for treating
      patients with actinic cheilitis included in this sample.

PMID- 27864998
TI  - RNF43 mutation frequently occurs with GNAS mutation and mucin hypersecretion in
      intraductal papillary neoplasms of the bile duct.
AB  - AIMS: RNF43 is a tumour suppressor gene that suppresses the Wnt-beta-catenin
      signalling pathway. We investigated the role of RNF43 in intraductal papillary
      neoplasm of the bile duct (IPNB). METHODS AND RESULTS: We conducted mutation
      analysis of RNF43 in 50 IPNBs, and identified six (12%) RNF43 mutations. RNF43
      mutation was more frequent in the intestinal subtype of IPNB (17%) than in the
      gastric/pancreatobiliary subtype (5%). There was a strong association of RNF43
      mutation with GNAS (P = 0.007) mutation, and a borderline correlation with KRAS
      (P = 0.074) mutation. The presence of macroscopic mucin hypersecretion was
      closely related to RNF43 (P = 0.024) and GNAS (P < 0.001) mutations. A two-step
      clustering analysis algorithm successfully categorized IPNBs into two subgroups
      by using the clinicopathological and molecular features of IPNBs. One subgroup of
      IPNB represented the 'biliary counterpart of intraductal papillary mucinous
      neoplasm of the pancreas' (biliary-IPMN), and showed unique features reminiscent
      of IPMN, such as macroscopic and microscopic mucin hypersecretion, an intestinal
      cell lineage, GNAS mutation, and RNF43 mutation. Biliary-IPMNs were significantly
      associated with high expression of cytokeratin (CK) 20, mucin 2 (MUC2), and CDX2,
      as shown by immunostaining (P = 0.032, P = 0.001, and P = 0.026, respectively),
      and had a borderline association with low expression of CK7 (P = 0.063). With the
      use of this splitting algorithm, RNF43 mutations were identified in 36% of the
      biliary-IPMNs. CONCLUSIONS: The identification of RNF43 mutations in a distinct
      subset of IPNBs revealed a new molecular role in the pathogenesis of IPNB, and
      provided a potential application for cancer therapeutics by the use of Wnt
      pathway inhibitors.

PMID- 27864999
TI  - A Synthetic Toolbox for the In Situ Formation of Functionalized Homo- and
      Heteropolysaccharide-Based Hydrogel Libraries.
AB  - A synthetic toolbox for the introduction of aldehydo and hydrazido groups into
      the polysaccharides hyaluronic acid, alginate, dextran, pullulan, glycogen, and
      carboxymethyl cellulose and their use for hydrogel formation is reported. Upon
      mixing differently functionalized polysaccharides derived from the same natural
      precursor, hydrazone cross-linking takes place, which results in formation of a
      hydrogel composed of one type of polysaccharide backbone. Likewise, hydrogels
      based on two different polysaccharide strands can be formed after mixing the
      corresponding aldehydo- and hydrazido-modified polysaccharides. A second line of
      these studies paves the way to introduce a biomedically relevant ligand, namely,
      the adhesion factor cyclic RGD pentapeptide, by using an orthogonal click
      reaction. This set of modified polysaccharides served to create a library of
      hydrogels that differ in the combination of polysaccharide strands and the degree
      of cross-linking. The different hydrogels were evaluated with respect to their
      rheological properties, their ability to absorb water, and their cytotoxicity
      towards human fibroblast cell cultures. None of the hydrogels studied were
      cytotoxic, and, hence, they are in principal biocompatible for applications in
      tissue engineering.

PMID- 27865000
TI  - Improving the quality of registered nurses' working time use data.
AB  - AIMS AND OBJECTIVES: To examine the advantages and disadvantages of external
      observation and self-reporting methods in investigating registered nurses'
      working time use in order to improve the quality of working time use data.
      BACKGROUND: External observation and self-reporting methods are the most widely
      used approaches for studying nurses' working time use in observational work
      sampling studies, but there is scarce information of the data collection
      procedures and results in the same research context and in the same study.
      DESIGN: A cross-sectional quantitative study with a structured data collection
      instrument developed for this study. The same instrument was used in both data
      collections. METHODS: Data were collected from six inpatient units at two Finnish
      tertiary hospitals in autumn 2013 over two consecutive weeks. All registered
      nurses (n = 95) from two internal medical units, two surgical units and two
      psychiatric units participated in this study. RESULTS: Statistically
      significantly divergent information was produced by the two data collection
      methods in the major nursing categories of value-adding care and non-value-adding
      work as well as in each of the seven nursing subcategories. CONCLUSIONS: External
      observation and self-reporting gave an overall picture of how registered nurses
      are using their working time, and both methods were useful in examining
      registered nurses' working time use when taking into account the advantages and
      disadvantages of these methods. The deviations between the results improved the
      quality of data because both methods address recognised shortcomings of the
      other. RELEVANCE TO CLINICAL PRACTICE: This research promotes awareness of the
      divergent study results by investigating registered nurses' working time use with
      these two different data collection methods. In future, it would be wise to aim
      for more comparable data by applying external observation and self-reporting
      techniques simultaneously.

PMID- 27865001
TI  - Romosozumab Improves Bone Mass and Strength While Maintaining Bone Quality in
      Ovariectomized Cynomolgus Monkeys.
AB  - Romosozumab (Romo), a humanized sclerostin antibody, is a bone-forming agent
      under development for treatment of osteoporosis. To examine the effects of Romo
      on bone quality, mature cynomolgus monkeys (cynos) were treated 4 months post-
      ovariectomy (OVX) with vehicle, 3 mg/kg, or 30 mg/kg Romo for 12 months, or with
      30 mg/kg Romo for 6 months followed by vehicle for 6 months (30/0). Serum bone
      formation markers were increased by Romo during the first 6 months, corresponding
      to increased cancellous, endocortical, and periosteal bone formation in rib and
      iliac biopsies at months 3 and 6. Dual-energy X-ray absorptiometry (DXA) bone
      mineral density (BMD) was increased by 14% to 26% at the lumbar spine and
      proximal femur at month 12, corresponding to significant increases in bone
      strength at 3 and 30 mg/kg in lumbar vertebral bodies and cancellous cores, and
      at 30 mg/kg in the femur diaphysis and neck. Bone mass remained positively
      correlated with strength at these sites, with no changes in calculated material
      properties at cortical sites. These bone-quality measures were also maintained in
      the 30/0 group, despite a gradual loss of accrued bone mass. Normal bone
      mineralization was confirmed by histomorphometry and ash analyses. At the radial
      diaphysis, a transient, reversible 2% reduction in cortical BMD was observed with
      Romo at month 6, despite relative improvements in bone mineral content (BMC).
      High-resolution pQCT confirmed this decline in cortical BMD at the radial
      diaphysis and metaphysis in a second set of OVX cynos administered 3 mg/kg Romo
      for 6 months. Radial diaphyseal strength was maintained and metaphyseal strength
      improved with Romo as estimated by finite element modeling. Decreased radial
      cortical BMD was a consequence of increased intracortical remodeling, with no
      increase in cortical porosity. Romo resulted in marked improvements in bone mass,
      architecture, and bone strength, while maintaining bone quality in OVX cynos,
      supporting its bone efficacy and safety profile. (c) 2016 American Society for
      Bone and Mineral Research.

PMID- 27865002
TI  - Gold(I) NHC Complexes: Antiproliferative Activity, Cellular Uptake, Inhibition of
      Mammalian and Bacterial Thioredoxin Reductases, and Gram-Positive Directed
      Antibacterial Effects.
AB  - Gold complexes with N-heterocyclic carbene (NHC) ligands represent a promising
      class of metallodrugs for the treatment of cancer or infectious diseases. In this
      report, the synthesis and the biological evaluation of halogen-containing NHC-AuI
      -Cl complexes are described. The complexes 1 and 5 a-5 f displayed good cytotoxic
      activity against tumor cells, and cellular uptake studies suggested that an
      intact Au-NHC fragment is essential for the accumulation of high amounts of both
      the metal and the NHC ligand. However, the bioavailability was negatively
      affected by serum components of the cell culture media and was influenced by
      likely transformations of the complex. One example (5 d) efficiently induced
      apoptosis in vincristine- and daunorubicin-resistant P-glycoprotein
      overexpressing Nalm-6 leukemia cells. Cellular uptake studies with this compound
      showed that both the wild-type and resistant Nalm-6 cells accumulated comparable
      amounts of gold, indicating that the gold drug was not excreted by P-glycoprotein
      or other efflux transporters. The effective inhibition of mammalian and bacterial
      thioredoxin reductases (TrxR) was confirmed for all of the gold complexes.
      Antibacterial screening of the gold complexes showed a particularly high activity
      against Gram-positive strains, reflecting their high dependence on an intact
      Trx/TrxR system. This result is of particular interest as the inhibition of
      bacterial TrxR represents a relatively little explored mechanism of new anti
      infectives.

PMID- 27865003
TI  - Capturing early signs of deterioration: the dutch-early-nurse-worry-indicator
      score and its value in the Rapid Response System.
AB  - AIMS AND OBJECTIVES: To determine the predictive value of individual and combined
      dutch-early-nurse-worry-indicator-score indicators at various Early Warning Score
      levels, differentiating between Early Warning Scores reaching the trigger
      threshold to call a rapid response team and Early Warning Score levels not
      reaching this point. BACKGROUND: Dutch-early-nurse-worry-indicator-score
      comprises nine indicators underlying nurses' 'worry' about a patient's condition.
      All indicators independently show significant association with unplanned
      intensive care/high dependency unit admission or unexpected mortality. Prediction
      of this outcome improved by adding the dutch-early-nurse-worry-indicator-score
      indicators to an Early Warning Score based on vital signs. DESIGN: An
      observational cohort study was conducted on three surgical wards in a tertiary
      university-affiliated teaching hospital. METHODS: Included were surgical, native
      speaking, adult patients. Nurses scored presence of 'worry' and/or dutch-early
      nurse-worry-indicator-score indicators every shift or when worried. Vital signs
      were measured according to the prevailing protocol. Unplanned intensive care/high
      dependency unit admission or unexpected mortality was the composite endpoint.
      Percentages of 'worry' and dutch-early-nurse-worry-indicator-score indicators
      were calculated at various Early Warning Score levels in control and event
      groups. Entering all dutch-early-nurse-worry-indicator-score indicators in a
      multiple logistic regression analysis, we calculated a weighted score and
      calculated sensitivity, specificity, positive predicted value and negative
      predicted value for each possible total score. RESULTS: In 3522 patients, 102
      (2.9%) had an unplanned intensive care/high dependency unit admissions (n = 97)
      or unexpected mortality (n = 5). Patients with such events and only slightly
      changed vital signs had significantly higher percentages of 'worry' and dutch
      early-nurse-worry-indicator-score indicators expressed than patients in the
      control group. Increasing number of dutch-early-nurse-worry-indicator-score
      indicators showed higher positive predictive values. CONCLUSIONS: Dutch-early
      nurse-worry-indicator-score indicators alert in an early stage of deterioration,
      before reaching the trigger threshold to call a rapid response team and can
      improve interdisciplinary communication on surgical wards during regular rounds,
      and when calling for assistance. RELEVANCE TO CLINICAL PRACTICE: Dutch-early
      nurse-worry-indicator-score structures communication and recording of signs known
      to be associated with a decline in a patient's condition and can empower nurses
      to call assistance on the 'worry' criterion in an early stage of deterioration.

PMID- 27865004
TI  - Long-term effects of high-intensity interval training in heart transplant
      recipients: A 5-year follow-up study of a randomized controlled trial.
AB  - BACKGROUND: Previous studies have demonstrated that high-intensity interval
      training (HIT) is superior to moderate-continuous exercise in general and in
      cardiovascular diseases. Recently, we also found HIT safe and efficient after
      heart transplantation (HTx). This study reports the 5-year long-term effects.
      DESIGN AND METHODS: Forty-one HTx patients who had completed the previous 12
      month randomized controlled trial, comparing HIT intervention with usual care,
      were eligible. In particular, we measured VO2peak , muscular capacity,
      intravascular ultrasound, and questionnaires measuring physical and mental
      health. RESULTS: The baseline mean+/-SD values were as follows: age; 49.1+/-16.5
      years, men; 68%, time since HTx: 4.1+/-2.2 years. Within the HIT group, initial
      VO2peak increased significantly from 27.7+/-5.7 to 31.2+/-5.3 mL/kg/min. However,
      during the next 4 years, VO2peak decreased to 26.0+/-6.2 mL/kg/min. The control
      group showed slightly decreasing VO2peak values during the entire 5-year period.
      The HIT group reported significantly less anxiety symptoms, but there were no
      long-term differences in VO2peak , muscular capacity, or cardiac allograft
      vasculopathy between the groups. The similar VO2peak values correspond to our
      findings of similar everyday activity. CONCLUSION: Our findings suggest that
      intermittent periods of HIT may be necessary to maintain the initial benefits
      gained from the intervention. However, HIT probably reduces the burden of
      anxiety, which is a frequent health issue following HTx.

PMID- 27865005
TI  - Hydrogenated Bismuth Molybdate Nanoframe for Efficient Sunlight-Driven Nitrogen
      Fixation from Air.
AB  - Sunlight-driven dinitrogen fixation can lead to a novel concept for the
      production of ammonia under mild conditions. However, the efficient artificial
      photosynthesis of ammonia from ordinary air (instead of high pure N2 ) has never
      been implemented. Here, we report for the first time the intrinsic catalytic
      activity of Bi2 MoO6 catalyst for direct ammonia synthesis under light
      irradiation. The edge-exposed coordinatively unsaturated Mo atoms in an Mo-O
      coordination polyhedron can act as activation centers to achieve the
      chemisorption, activation, and photoreduction of dinitrogen efficiently. Using
      that insight as a starting point, through rational structure and defect
      engineering, the optimized Bi2 MoO6 sunlight-driven nitrogen fixation system,
      which simultaneously possesses robust nitrogen activation ability, excellent
      light-harvesting performance, and efficient charge transmission was successfully
      constructed. As a surprising achievement, this photocatalytic system demonstrated
      for the first time ultra-efficient (1.3 mmol g-1  h-1 ) and stable sunlight
      driven nitrogen fixation from air in the absence of any organic scavengers.

PMID- 27865006
TI  - Soft Microrobots Employing Nonequilibrium Actuation via Plasmonic Heating.
AB  - A soft microrobot composed of a microgel and driven by the light-controlled
      nonequilibrium dynamics of volume changes is presented. The photothermal response
      of the microgel, containing plasmonic gold nanorods, enables fast heating/cooling
      dynamics. Mastering the nonequilibrium response provides control of the complex
      motion, which goes beyond what has been so far reported for hydrophilic
      microgels.

PMID- 27865008
TI  - Biosynthesis of the psychotropic plant diterpene salvinorin A: Discovery and
      characterization of the Salvia divinorum clerodienyl diphosphate synthase.
AB  - Salvia divinorum commonly known as diviner's sage, is an ethnomedicinal plant of
      the mint family (Lamiaceae). Salvia divinorum is rich in clerodane-type
      diterpenoids, which accumulate predominantly in leaf glandular trichomes. The
      main bioactive metabolite, salvinorin A, is the first non-nitrogenous natural
      compound known to function as an opioid-receptor agonist, and is undergoing
      clinical trials for potential use in treating neuropsychiatric diseases and drug
      addictions. We report here the discovery and functional characterization of two
      S. divinorum diterpene synthases (diTPSs), the ent-copalyl diphosphate (ent-CPP)
      synthase SdCPS1, and the clerodienyl diphosphate (CLPP) synthase SdCPS2. Mining
      of leaf- and trichome-specific transcriptomes revealed five diTPSs, two of which
      are class II diTPSs (SdCPS1-2) and three are class I enzymes (SdKSL1-3). Of the
      class II diTPSs, transient expression in Nicotiana benthamiana identified SdCPS1
      as an ent-CPP synthase, which is prevalent in roots and, together with SdKSL1,
      exhibits a possible dual role in general and specialized metabolism. In vivo co
      expression and in vitro assays combined with nuclear magnetic resonance (NMR)
      analysis identified SdCPS2 as a CLPP synthase. A role of SdCPS2 in catalyzing the
      committed step in salvinorin A biosynthesis is supported by its biochemical
      function, trichome-specific expression and absence of additional class II diTPSs
      in S. divinorum. Structure-guided mutagenesis revealed four catalytic residues
      that enabled the re-programming of SdCPS2 activity to afford four distinct
      products, thus advancing our understanding of how neo-functionalization events
      have shaped the array of different class II diTPS functions in plants, and may
      promote synthetic biology platforms for a broader spectrum of diterpenoid
      bioproducts.

PMID- 27865009
TI  - Melatonin synergizes the chemotherapeutic effect of 5-fluorouracil in colon
      cancer by suppressing PI3K/AKT and NF-kappaB/iNOS signaling pathways.
AB  - 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents in
      colon cancer treatment, but has a narrow therapeutic index limited by its
      toxicity. Melatonin exerts antitumor activity in various cancers, but it has
      never been combined with 5-FU as an anticolon cancer treatment to improve the
      chemotherapeutic effect of 5-FU. In this study, we assessed such combinational
      use in colon cancer and investigated whether melatonin could synergize the
      antitumor effect of 5-FU. We found that melatonin significantly enhanced the 5-FU
      mediated inhibition of cell proliferation, colony formation, cell migration and
      invasion in colon cancer cells. We also found that melatonin synergized with 5-FU
      to promote the activation of the caspase/PARP-dependent apoptosis pathway and
      induce cell cycle arrest. Further mechanism study demonstrated that melatonin
      synergized the antitumor effect of 5-FU by targeting the PI3K/AKT and NF
      kappaB/inducible nitric oxide synthase (iNOS) signaling. Melatonin in combination
      with 5-FU markedly suppressed the phosphorylation of PI3K, AKT, IKKalpha,
      IkappaBalpha, and p65 proteins, promoted the translocation of NF-kappaB p50/p65
      from the nuclei to cytoplasm, abrogated their binding to the iNOS promoter, and
      thereby enhanced the inhibition of iNOS signaling. In addition, pretreatment with
      a PI3K- or iNOS-specific inhibitor synergized the antitumor effects of 5-FU and
      melatonin. Finally, we verified in a xenograft mouse model that melatonin and 5
      FU exerted synergistic antitumor effect by inhibiting the AKT and iNOS signaling
      pathways. Collectively, our study demonstrated that melatonin synergized the
      chemotherapeutic effect of 5-FU in colon cancer through simultaneous suppression
      of multiple signaling pathways.

PMID- 27865010
TI  - A mixed-methods study exploring sign-off mentorship practices in relation to the
      Nursing and Midwifery Council standards.
AB  - AIMS AND OBJECTIVES: To investigate the current practice and experience of sign
      off mentors in one NHS trust. BACKGROUND: In the UK, sign-off mentors support
      nursing students in their last clinical placement and are accountable for the
      final assessment of fitness to practice as a registered nurse. DESIGN: Mixed
      methods study. METHODS: The focus was on two key Nursing and Midwifery Council
      standards: the requirement for students to work at least 40% of their time on
      clinical placement with a sign-off mentor/mentor; the sign-off mentor had one
      hour-per-week protected time to meet the final placement student. Data were
      collected through two audits of clinical and university documents and an
      experience survey administered to all sign-off mentors in one trust. RESULTS: The
      audits showed that only 22/42 (52%) of students were supervised by their sign-off
      mentor/mentor at least 40% of the time, whilst 10/42 (24%) students never worked
      a shift with their sign-off mentor. Only one student met their sign-off mentor
      every week. Complete data were available in 31/64 (47%) sign-off mentors, of whom
      21/30 (70%) rarely/never had reduced clinical commitment to mentor final
      placement students. Furthermore, 19/28 (68%) met their student after their shift
      had ended with 24/30 (80%) reporting not getting any protected time. CONCLUSION:
      Sign-off mentors have inadequate time and resources to undertake their role, yet
      are accountable for confirming the student has the required knowledge and skills
      to practise safely. The current model needs urgent review to improve mentoring
      standards. RELEVANCE TO CLINICAL PRACTICE: Understanding how the role of the sign
      off mentor is working in practice is critical to ensuring that the Nursing and
      Midwifery Council standards are met, ensuring students are well supported and
      appropriately assessed in practice, and mentoring is given the high profile it
      deserves to guarantee high-quality care and protecting the public.

PMID- 27865007
TI  - Anisotropic Materials for Skeletal-Muscle-Tissue Engineering.
AB  - Repair of damaged skeletal-muscle tissue is limited by the regenerative capacity
      of the native tissue. Current clinical approaches are not optimal for the
      treatment of large volumetric skeletal-muscle loss. As an alternative, tissue
      engineering represents a promising approach for the functional restoration of
      damaged muscle tissue. A typical tissue-engineering process involves the design
      and fabrication of a scaffold that closely mimics the native skeletal-muscle
      extracellular matrix (ECM), allowing organization of cells into a physiologically
      relevant 3D architecture. In particular, anisotropic materials that mimic the
      morphology of the native skeletal-muscle ECM, can be fabricated using various
      biocompatible materials to guide cell alignment, elongation, proliferation, and
      differentiation into myotubes. Here, an overview of fundamental concepts
      associated with muscle-tissue engineering and the current status of muscle-tissue
      engineering approaches is provided. Recent advances in the development of
      anisotropic scaffolds with micro- or nanoscale features are reviewed, and how
      scaffold topographical, mechanical, and biochemical cues correlate to observed
      cellular function and phenotype development is examined. Finally, some recent
      developments in both the design and utility of anisotropic materials in skeletal
      muscle-tissue engineering are highlighted, along with their potential impact on
      future research and clinical applications.

PMID- 27865011
TI  - Vital signs as predictors for aggression in hospital patients (VAPA).
AB  - AIMS AND OBJECTIVES: To examine and describe the relationship between
      physiological status and violent and aggressive behaviours in hospital patients.
      BACKGROUND: The majority of adverse events are preceded by physiological
      abnormalities; whether physiological deterioration is a predictor of violent or
      aggressive behaviours remains unknown. DESIGN: Prospective case-control study.
      METHODS: Prospective audit of 999 patients from two major health services in
      Melbourne, Australia. There were 333 cases who required an emergency response for
      aggressive or violent behaviour (Code Grey) in the emergency department, medical
      or surgical units, or inpatient mental health unit between January-June 2015. Two
      control patients who did not have a Code Grey were randomly selected from the
      same unit and same day that the Code Grey occurred for the case patient. RESULTS:
      Patient locations were 54.4% medical or surgical units, 23.7% emergency
      department and 21.9% mental health units. Code Grey patients had less
      documentation of physiological assessment and were more likely to have
      respiratory rate, heart rate and conscious state abnormalities in the 12 hours
      preceding Code Grey. After adjusting for confounders, the risk of Code Grey was
      highest for patients with confusion. CONCLUSION: Patients experiencing
      behavioural disturbance had lower standards of patient assessment, greater
      incidence of physiological abnormalities and more inpatient deaths. Early
      recognition of, and response to, patient and physiological predictors of Code
      Grey should be a strategy to prevent behavioural escalation to the point of Code
      Grey. RELEVANCE TO CLINICAL PRACTICE: Strategies are needed to improve
      physiological assessment of patients with behavioural disturbance while ensuring
      staff safety. There are patient and physiological factors associated with
      increased risk of Code Grey that may be used to prevent behavioural escalation to
      the point of an emergency response.

PMID- 27865012
TI  - Half-Sandwich Alkyl, Amido, and Iodo Samarium(II) Complexes: Non-Conventional
      Sterically Governed Oxidation of (tBu4 Carb)2 Sm.
AB  - The half-sandwich tetra-tert-butylcarbazol-9-yl iodo complex [(tBu4 Carb)Sm(MU
      I)(THF)2 ]2 (1) was synthesized by the salt metathesis reaction of tBu4 CarbK and
      SmI2 (THF)2 in THF. Complex 1 along with metallic Cu was also isolated from the
      oxidation reaction of (tBu4 Carb)2 Sm by CuI. The formation of stable radical
      tBu4 Carb. was detected in this non-conventional process, indicating preferential
      oxidation of anion tBu4 Carb- vs. SmII . The treatment of 1 with two equivalents
      of dibenzo-18-crown-6 resulted in heterolytic dissociation of a eta5 -bond Sm
      tBu4 Carb and afforded an ionic compound [tBu4 carb- ][SmI(crown)(THF)2 ]+ (4).
      Alkylation of 1 with o-NMe2 C6 H4 CH2 K (1:2 molar ratio) in THF allowed for the
      synthesis of half-sandwich SmII alkyl complex (tBu4 Carb)SmCH2 (o-NMe2 C6 H4 CH2
      )(THF)2 (5) in 55 % yield. The amido complex (tBu4 Carb)SmN(SiMe3 )2 (DME) (6)
      was obtained by the reaction of 1 with two molar equivalents of NaN(SiMe3 )2 in
      THF in 89 % yield.

PMID- 27865013
TI  - Dancing around families: neonatal nurses and their role in child protection.
AB  - AIMS AND OBJECTIVES: To explore the processes neonatal intensive care nurses used
      in their child protection role with preterm infants. BACKGROUND: Neonatal nurses'
      screening for family violence is important in identifying at-risk preterm infants
      requiring protection upon discharge from neonatal intensive care settings. We
      know little about neonatal nurses and their role in child protection. DESIGN: A
      qualitative research design using Glaserian grounded theory. METHODS: Ten in
      depth semi-structured interviews were conducted with New Zealand neonatal
      intensive care nurses. Data were simultaneously analysed using constant
      comparative analysis and theoretical sampling to develop a substantive grounded
      theory. RESULTS: Dancing around families is the substantive grounded theory
      explaining how neonatal intensive care nurses respond to and manage an infant
      needing child protection. Knowing at-risk families is the process these nurses
      used, which draws on their personal and professional knowledge to identify an
      infant's child welfare requirements. A tension exists for neonatal nurses in
      shaping and framing the baby's safety and protection needs between their role of
      nurturing and protecting an at-risk infant and it belonging to the family.
      CONCLUSIONS: Child protection is a source of conflict for neonatal intensive care
      nurses. A lack of education, dodgy families and lack of confidence in child
      welfare services all compromise effective child protection. Their reality is
      tension between wanting the best possible outcomes for the baby, but having
      little or no control over what happens following its discharge. RELEVANCE TO
      CLINICAL PRACTICE: Neonatal intensive care nurses are ideally positioned to
      identify and respond to those preterm infants at risk of child maltreatment. They
      need education in child maltreatment, and protection focused on preterm infants,
      collegial support and clinical supervision.

PMID- 27865014
TI  - OFF-ON-OFF Red-Emitting Fluorescent Indicators for a Narrow pH Window.
AB  - A unique combination of two independent mechanisms of fluorescence quenching,
      namely intramolecular charge transfer (ICT) from a peripheral donor and
      protonation of azomethine nitrogen atoms in zinc tetrapyrazinoporphyrazines
      (TPyzPz), provides a new possibility for sensing pH in a specific range. The pH
      selectivity was controlled by the different basicities of the donor for ICT
      (dimethylaminoaryl), which was connected to the macrocycle by pi-extended linkers
      of different lengths. ICT and protonation have been studied in detail by
      photophysical, spectral (UV/Vis and MCD spectra), and electrochemical
      measurements, and further supported by theoretical calculations (DFT, TDDFT). The
      pH-sensing properties of the TPyzPzs have been investigated in THF and in water
      after anchoring the TPyzPzs to liposomes. The salient pKa values were around 1.3
      (azomethine nitrogen) and 2.29-4.76 (donor for ICT). The lead indicators (sensing
      over a pH range of 1.0-2.5) with fairly steep sensing profiles exhibited
      increases in fluorescence between the OFF/ON states of more than 20-fold and
      strong absorption in the red region (Q-band maximum >650 nm, epsilon~2*106  m-1 
      cm-1 ).

PMID- 27865016
TI  - Bimetal-Organic Framework Derived CoFe2 O4 /C Porous Hybrid Nanorod Arrays as
      High-Performance Electrocatalysts for Oxygen Evolution Reaction.
AB  - Porous CoFe2 O4 /C NRAs supported on nickel foam@NC (denoted as NF@NC-CoFe2 O4 /C
      NRAs) are directly fabricated by the carbonization of bimetal-organic framework
      NRAs grown on NF@poly-aniline(PANI), and they exhibit high electrocatalytic
      activity, low overpotential, and high stability for the oxygen evolution reaction
      in alkaline media.

PMID- 27865017
TI  - Isolated thoughts and feelings and unsolved concerns: adolescents' and parents'
      perspectives on living with type 1 diabetes - a qualitative study using visual
      storytelling.
AB  - AIMS AND OBJECTIVES: To explore and describe the experiences of adolescents and
      their parents living with type 1 diabetes, to identify their needs for support to
      improve adolescents' self-management skills in the transition from child- to
      adulthood. BACKGROUND: Adolescents with type 1 diabetes often experience
      deteriorating glycaemic control and distress. Parents are important in
      adolescents' ability to self-manage type 1 diabetes, but they report anxiety and
      frustrations. A better understanding of the challenges adolescents and parents
      face, in relation to the daily self-management of type 1 diabetes, is important
      to improve clinical practice. DESIGN: A qualitative explorative study using
      visual storytelling as part of individual interviews. METHODS: A purposive sample
      of nine adolescents and their parents (seven mothers, six fathers) took
      photographs illustrating their experiences living with type 1 diabetes.
      Subsequently, participants were interviewed individually guided by participants'
      photographs and a semistructured interview guide. Interviews were analysed using
      thematic analysis. RESULTS: Four major themes were consistent across adolescents
      and their parents: (1) striving for safety, (2) striving for normality, (3)
      striving for independence and (4) worrying about future. Although adolescents and
      parents had same concerns and challenges living with type 1 diabetes, they were
      experienced differently. Their thoughts and feelings mostly remained isolated and
      their concerns and challenges unsolved. CONCLUSIONS: The concerns and challenges
      adolescents and their parents face in the transition from child- to adulthood are
      still present despite new treatment modalities. Parents are fundamental in
      supporting the adolescents' self-management-work; however, the parties have
      unspoken concerns and challenges. RELEVANCE TO CLINICAL PRACTICE: Healthcare
      providers should address the parties' challenges and concerns living with type 1
      diabetes to diminish worries about future including fear of hypoglycaemia, the
      burden of type 1 diabetes and the feeling of being incompetent in diabetes self
      management. It is important to focus on supporting both adolescents and their
      parents, and to provide a shared platform for communication.

PMID- 27865015
TI  - Cannabis use during treatment for alcohol use disorders predicts alcohol
      treatment outcomes.
AB  - AIMS: To compare post-treatment alcohol use between those who use cannabis and
      those who abstain during treatment for alcohol use disorders (AUD); and to
      examine potential cannabis use thresholds by comparing post-treatment alcohol use
      between four frequency groups of cannabis users relative to abstainers. DESIGN:
      Secondary analyses of the Combined Pharmacotherapies and Behavioral Interventions
      (COMBINE) Study, a randomized control trial of AUD treatments. The current study
      compares longitudinal drinking data between those who used cannabis versus those
      who abstained during COMBINE treatment. SETTING: The COMBINE Study treatments
      were delivered on an out-patient basis for 16 weeks. The current analyses include
      206 cannabis users and 999 cannabis abstainers. PARTICIPANTS: All participants
      met diagnosis of primary alcohol dependence (n = 1383). MEASUREMENTS: Primary
      exposures were any cannabis use and quartiles of cannabis use (Q1: 1-4 use days
      during treatment, Q2: 5-9 days, Q3: 10-44 days, Q4: 45-112 days). Outcomes were
      percentage of days abstinent from alcohol (PDA), drinks per drinking day (DPDD)
      and percentage of heavy drinking days (PHD), all measured at treatment end and 1
      year post-treatment. FINDINGS: Compared with no cannabis use, any cannabis use
      during treatment was associated with 4.35% [95% confidence interval (CI) = -8.68,
      -0.02], or approximately 4 fewer alcohol abstinent days at the end of treatment.
      This association weakened by 1 year post-treatment (95% CI = -9.78, 0.54).
      Compared with no cannabis use, only those in the second quartile of cannabis use
      (those who used once or twice per month during treatment) had 8.81% (95% CI = 
      17.00, -0.63), or approximately 10 fewer days alcohol abstinent at end of
      treatment, and 11.82% (95% CI = -21.56, -2.07), or approximately 13 fewer alcohol
      abstinent days 1 year post-treatment. Neither any cannabis use nor quartiles were
      associated with DPDD or PHD at either time-point. CONCLUSIONS: Among individuals
      in alcohol treatment, any cannabis use (compared with none) is related to a
      significantly lower percentage of days abstinent from alcohol post-treatment,
      although only among those who used cannabis once or twice per month.

PMID- 27865018
TI  - How Would Rural Hospitals Be Affected by Loss of the Affordable Care Act's
      Medicare Low-Volume Hospital Adjustment?
AB  - PURPOSE: The low-volume hospital (LVH) payment adjustment established in the
      Patient Protection and Affordable Care Act (ACA) of 2010 is scheduled to sunset
      on October 1, 2017. The purpose of this analysis was: (1) to estimate the effect
      of the ACA LVH adjustment on qualifying hospitals' profitability margins; and (2)
      to examine hospital and market characteristics of the hospitals that would be
      most adversely affected by the loss of the ACA LVH adjustment. METHODS: 2004-2015
      data from the Hospital Cost Report Information System, Hospital Market Service
      Area File and Nielsen-Claritas Pop-Facts file were used to estimate difference-in
      difference regression models with hospital-level random effects in order to
      determine whether the ACA LVH adjustment improved qualifying rural hospitals'
      profitability margins. Recycled predictions estimated the effect of losing the
      ACA LVH adjustment on profitability margins. Bivariate analyses explored
      associations between the predicted profitability margins and hospital and market
      characteristics. FINDINGS: The ACA LVH adjustment significantly improved Sole
      Community Hospitals' Medicare inpatient margins in the year they received the
      adjustment, and it had a large but statistically insignificant effect on the
      profitability margins of other rural hospitals. Hospitals that would be the most
      adversely affected by loss of the ACA LVH adjustment were more likely to be
      small, located in the South, and in high-poverty markets with higher proportions
      of black and uninsured individuals. CONCLUSIONS: Elimination of the ACA LVH
      adjustment would have differential effects on subgroups of hospitals, and those
      located in markets serving historically underserved populations would be the most
      adversely affected.

PMID- 27865019
TI  - The regulation of carotenoid formation in tomato fruit.
AB  - Carotenoid biosynthesis in plants includes a complex series of
      desaturation/isomerisation reactions, catalyzed by four independent enzymes. In
      bacteria and fungi one desaturase/isomerase enzyme completes the same series of
      reactions. In the present study, a bacterial desaturase (crtI) from Pantoea
      ananatis has been overexpressed in the tangerine mutant of tomato (Solanum
      lycopersicon) which accumulates cis-carotene isomers in the fruit due to a
      defective isomerase (CRTISO) and the old gold crimson (ogc ) tomato mutant, which
      is defective in the fruit-enhanced lycopene beta-cyclase (CYCB). Comprehensive
      molecular and biochemical characterization of the resulting lines expressing crtI
      has revealed negative feedback mechanisms, acting predominantly at the level of
      phytoene synthase-1 (PSY1), and feed-forward mechanisms inducing cyclisation. In
      both cases, altered transcription appears to be the progenitor, with subsequent
      post-transcriptional modulation highlighting the complexity of the processes
      involved in modulating carotenoid homeostasis in plant tissues.

PMID- 27865020
TI  - Nitrogen-Induced Transformation of Vitamin C into Multifunctional Up-converting
      Carbon Nanodots in the Visible-NIR Range.
AB  - Water-soluble, biocompatible, and photoluminescent carbon nanodots have been
      obtained from the rationalized carbonization of vitamin C, a well-known
      antioxidant molecule in the presence of an amine co-reactant. Herein, we describe
      the positive influence of N-doping to induce a unique pH-dependent lifetime decay
      response that would be potentially attractive in biological backgrounds with
      intrinsic fluorescence fluctuations. In addition, the selectivity and sensitivity
      of the N-containing carbon nanoprobes towards the detection of copper ions at ppm
      levels is critically enhanced in comparison with the un-doped counterpart,
      especially in the near-infrared (NIR) range. Finally, the up-converting
      properties have been also successfully applied to image tumor cells in the
      visible range and remarkably, in the NIR region in which minimal tissue or water
      absorption and maximum penetration depth are expected.

PMID- 27865022
TI  - Exploring the experiences of patients attending day hospitals in the rural
      Scotland: capturing the patient's voice.
AB  - AIMS AND OBJECTIVES: To understand the meaning of person-centred compassionate
      care for people attending day hospitals in rural Scotland. BACKGROUND: Increasing
      numbers of older people are living with chronic conditions and require support to
      live at home. Intermediate care services such as day hospitals can enable this.
      Much previous research about day hospitals focused on organisational aspects of
      care. This study set out to capture the voice of the patient using this service.
      DESIGN: A descriptive qualitative study. METHODS: Individual interviews were
      undertaken in participant's homes using emotional touchpoints as prompts to help
      patients discuss their experience of care within a day hospital (n = 15). Data
      were analysed using thematic analysis. RESULTS: Four main themes were identified
      from the data: Relationships, Feeling Valued, Expectations and Perceived
      Benefits. The findings showed that relationships with staff and other patients
      were important. The patients also wanted to feel valued, and helping others was
      part of this. The patients had clear expectations of the service but had an acute
      awareness of the benefits of attending the day hospital such as coordination of
      their care. Overall, the patients were highly satisfied, felt that care was
      person-centred and recognised the advantages of remaining close to home.
      CONCLUSIONS: At a time when enabling health and social care integration is a
      priority, this study provides insight into the patient perspective of
      intermediate care. The findings reveal what matters to patients cared for in the
      community and how this service can respond to this. RELEVANCE TO CLINICAL
      PRACTICE: This study provides insight for healthcare practitioners caring for
      patients in the community and those responsible for planning and resourcing this
      service. It should also start a dialogue about how these services could be used
      more.

PMID- 27865021
TI  - Ligand binding specificity of the Escherichia coli periplasmic histidine binding
      protein, HisJ.
AB  - The HisJ protein from Escherichia coli and related Gram negative bacteria is the
      periplasmic component of a bacterial ATP-cassette (ABC) transporter system.
      Together these proteins form a transmembrane complex that can take up L-histidine
      from the environment and translocate it into the cytosol. We have studied the
      specificity of HisJ for binding L-His and many related naturally occurring
      compounds. Our data confirm that L-His is the preferred ligand, but that 1-methyl
      L-His and 3-methyl-L-His can also bind, while the dipeptide carnosine binds
      weakly and D-histidine and the histidine degradation products, histamine,
      urocanic acid and imidazole do not bind. L-Arg, homo-L-Arg, and post
      translationally modified methylated Arg-analogs also bind with reasonable
      avidity, with the exception of symmetric dimethylated-L-Arg. In contrast, L-Lys
      and L-Orn have considerably weaker interactions with HisJ and methylated and
      acetylated Lys variants show relatively poor binding. It was also observed that
      the carboxylate group of these amino acids and their variants was very important
      for proper recognition of the ligand. Taken together our results are a key step
      towards designing HisJ as a specific protein-based reagentless biosensor.

PMID- 27865023
TI  - Layered Post-Transition-Metal Dichalcogenides (X-M-M-X) and Their Properties.
AB  - AIII BVI chalcogenides are an interesting group of layered semiconductors with
      several attractive properties, such as tunable band gaps and the formation of
      solid solutions. Unlike the typically sandwiched structure of transition-metal
      dichalcogenides, AIII BVI layered chalcogenides with hexagonal symmetry are
      stacked through the X-M-M-X motif, in which M is gallium and indium, and X is
      sulfur, selenium, and tellurium. In view of the inadequate study of the
      electrochemical properties and great interest in layered materials towards energy
      related research, herein the inherent electrochemistry of GaS, GaSe, GaTe, and
      InSe has been studied, as well as the exploration of their potential as hydrogen
      evolution reaction (HER) electrocatalysts. All four materials show redox peaks
      during cyclic voltammetry measurements. Furthermore, insights into catalysis of
      the HER are provided; these indicate the conductivity and number of active sites
      of the materials. All of these findings have important implications on their
      possible applications.

PMID- 27865024
TI  - Impact of the zero-markup drug policy on hospitalisation expenditure in western
      rural China: an interrupted time series analysis.
AB  - OBJECTIVES: To assess the long-term effects of the introduction of China's zero
      markup drug policy on hospitalisation expenditure and hospitalisation
      expenditures after reimbursement. METHODS: An interrupted time series was used to
      evaluate the impact of the zero-markup drug policy on hospitalisation expenditure
      and hospitalisation expenditure after reimbursement at primary health
      institutions in Fufeng County of Shaanxi Province, western China. Two regression
      models were developed. Monthly average hospitalisation expenditure and monthly
      average hospitalisation expenditure after reimbursement in primary health
      institutions were analysed covering the period 2009 through to 2013. RESULTS: For
      the monthly average hospitalisation expenditure, the increasing trend was slowed
      down after the introduction of the zero-markup drug policy (coefficient = -16.49,
      P = 0.009). For the monthly average hospitalisation expenditure after
      reimbursement, the increasing trend was slowed down after the introduction of the
      zero-markup drug policy (coefficient = -10.84, P = 0.064), and a significant
      decrease in the intercept was noted after the second intervention of changes in
      reimbursement schemes of the new rural cooperative medical insurance (coefficient
      = -220.64, P < 0.001). CONCLUSIONS: A statistically significant absolute decrease
      in the level or trend of monthly average hospitalisation expenditure and monthly
      average hospitalisation expenditure after reimbursement was detected after the
      introduction of the zero-markup drug policy in western China. However,
      hospitalisation expenditure and hospitalisation expenditure after reimbursement
      were still increasing. More effective policies are needed to prevent these costs
      from continuing to rise.

PMID- 27865025
TI  - MR targeted imaging for the expression of tenascin-C in myocardial infarction in
      vivo.
AB  - PURPOSE: To investigate the presence of viable myocardium in mice with acute
      myocardial infarction (MI) using a molecular targeted probe. MATERIALS AND
      METHODS: Super paramagnetic iron oxide (SPIO) nanoparticles and tenascin-C
      antibody were conjugated as an MRI probe. Fifteen mice with infarction were
      injected with SPIO-anti-tenascin-C (3 days [d], 5d, 7d after infarction; n = 5
      for each group). Another five mice with infarction (5d, n = 5) were injected with
      SPIO for comparison. In vivo MR (7 Tesla, fast low-angle shot multi-slice T2*
      sequence) was performed for tracing. Histological analysis was used to compare
      surviving cardiomyocytes with signal changes on MR. RESULTS: The mRNA expression
      of tenascin-C increased directly after MI and peaked at the fifth day (5d 24.29
      +/- 1.41 versus 3d 10.63 +/- 0.72, 7d 6.56 +/- 0.12; P < 0.01). T2 relaxation
      rate of synthesized SPIO-anti-tenascin-C was r2 = 338 mM-1 s-1 . After MR, the
      signal changes (contrast-to-noise ratio) of the research group were 3d 6.51 +/-
      1.13 versus 5d 14.06 +/- 3.19 versus 7d 5.02 +/- 2.65, P < 0.05. The MR signal
      showed a small decrease in the contrast group on 5d (research group 14.06 +/-
      3.19 versus contrast group 1.75 +/- 0.59, P < 0.05). CONCLUSION: Tenascin-C was
      expressed by surviving cardiomyocytes within the infarcted region. MR imaging
      with SPIO-anti-tenascin-C might be used to evaluate myocardial viability of MI
      patients before therapy. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J.
      MAGN. RESON. IMAGING 2017;45:1668-1674.

PMID- 27865026
TI  - Self-efficacy in the context of heart transplantation - a new perspective.
AB  - AIMS AND OBJECTIVES: An in-depth exploration of self-efficacy among heart
      transplant recipients by means of Bandura's self-efficacy theory. BACKGROUND: An
      essential component of chronic illness management is self-management, which
      refers to activities carried out by people to create order, structure and control
      in their lives. Self-efficacy is an important aspect of self-management, which
      seems to have become the main paradigm for long-term management after solid organ
      transplantation. DESIGN: A directed content analysis using Bandura's self
      efficacy theory. METHODS: Open-ended, in-depth interviews were conducted with 14
      heart transplant recipients at their 12-month follow-up after heart
      transplantation. RESULTS: This study generated the hypothesis that from the
      patients' perspective, self-efficacy after heart transplantation concerns
      balancing expectations to find the optimum level of self-efficacy. Performance
      accomplishment was found to have the greatest impact on self-efficacy, while its
      absence was the main source of disappointments. It was also revealed that the gap
      between performance accomplishment and efficacy expectations can be understood as
      uncertainty. CONCLUSIONS: It is essential to assess both expectations and
      disappointments from the patient perspective in order to promote an optimum level
      of self-efficacy among heart transplant recipients. This includes supporting the
      heart recipient to adopt mental and physical adjustment strategies to balance
      her/his expectations as a means of minimising disappointments. The understanding
      that uncertainty can undermine self-efficacy is crucial. RELEVANCE TO CLINICAL
      PRACTICE: The merging of the uncertainty in illness and self-efficacy theories
      provides an excellent framework for the provision of self-management support. In
      addition, focusing on a partnership between the transplant professionals and the
      recipient is essential because it minimises the use of a behavioural approach.

PMID- 27865028
TI  - Trends in tropical tree growth: re-analyses confirm earlier findings.
AB  - In a recent Opinion article, Brienen et al. (2016) raise doubts about our finding
      that tropical tree growth has not increased during 150 years of CO2 rise
      (Groenendijk et al., 2015; van der Sleen et al., 2015). They claim that our tree
      ring data contain evidence for historical growth stimulation that was concealed
      due to failing regeneration in several species. Here we show that (i) the
      correction method proposed by Brienen et al. induces a bias towards finding
      positive growth trends, (ii) the results of Brienen et al. rest on selective
      removal of species, (iii) there is a simple and effective way to accommodate
      effects of recruitment failure by subsetting data, and (iv) the application of
      this method confirms our earlier findings. Thus, our results are robust to
      effects of recruitment failure and our conclusions remain unchanged: we find no
      evidence for historical growth changes in our studied tree species.

PMID- 27865027
TI  - Assessment of active and inactive sacroiliitis in patients with ankylosing
      spondylitis using quantitative dynamic contrast-enhanced MRI.
AB  - PURPOSE: To investigate the feasibility of using quantitative dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) to differentiate the active and
      inactive stage of sacroiliitis and the correlation between quantitative
      parameters and disease activity as measured by clinical scores. MATERIALS AND
      METHODS: Forty-two patients with ankylosing spondylitis underwent DCE-MRI on a
      3.0T MRI unit. According to the results of the blood sedimentation rate (ESR), C
      reactive protein (CRP), and Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI), the patients were grouped into inactive and active groups.
      Pharmacokinetic models were used to generate the semiquantitative and
      quantitative hemodynamic parameters of DCE-MRI. The between-group differences
      were analyzed using the Wilcoxon rank sum test, and the correlations between the
      pharmacokinetic parameters and BASDAI score were analyzed using Spearman's
      correlation coefficient. The efficacies of different parameters in
      differentiating the active and inactive phase of sacroiliitis were evaluated and
      compared using receiver operator characteristics (ROC) curve analysis. RESULTS:
      Ktrans , Kep , Ve , time to peak (TTP), max concentration (MAX Conc), and area
      under the curve (AUC) of the active group were significantly higher than those of
      the inactive stage group (P < 0.05). There were significant correlations between
      all parameters and BASDAI (P < 0.05). AUC of the receiver operator
      characteristics curve (AUCR ) of different parameters were not statistically
      different (P >0.05), except between AUC and MAX Conc (P = 0.0012). CONCLUSION:
      Quantitative DCE-MRI parameters can differentiate between active and inactive
      ankylosing spondylitis. Among those, Ktrans had the highest correlation
      coefficient with the BASDAI score. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage
      2 J. MAGN. RESON. IMAGING 2017;46:71-78.

PMID- 27865029
TI  - Highly Intact and Pure Oxo-Functionalized Graphene: Synthesis and Electron-Beam
      Induced Reduction.
AB  - Controlling the chemistry of graphene is necessary to enable applications in
      materials and life sciences. Research beyond graphene oxide is targeted to avoid
      the highly defective character of the carbon framework. Herein, we show how to
      optimize the synthesis of oxo-functionalized graphene (oxo-G) to prepare high
      quality monolayer flakes that even allow for direct transmission electron
      microscopy investigation at atomic resolution (HRTEM). The role of undesired
      residuals is addressed and sources are eliminated. HRTEM provides clear evidence
      for the exceptional integrity of the carbon framework of such oxo-G sheets. The
      patchy distribution of oxo-functionality on the nm-scale, observed on our highly
      clean oxo-G sheets, corroborates theoretical predictions. Moreover, defined
      electron-beam irradiation facilitates gentle de-functionalization of oxo-G
      sheets, a new route towards clean graphene, which is a breakthrough for localized
      graphene chemistry.

PMID- 27865030
TI  - Functionalization of Unactivated C(sp3 )-H Bonds Using Metal-Carbene Insertion
      Reactions.
AB  - Versatile C-H insertions: Novel protocols for metal-carbene insertions using
      diazo compounds have been recently developed. Application of the respective
      rhodium and palladium catalytic systems allows formation of new carbon-carbon
      bonds in very good yields and selectivities.

PMID- 27865031
TI  - The predictability of mosquito abundance from daily to monthly timescales.
AB  - The prediction of mosquito abundance is of central interest in addressing
      mosquito population dynamics and in forecasting the associated emerging and re
      emerging diseases. However, little work has focused on the systematic evaluation
      of how well adult mosquito abundance can be predicted as a function of
      observational resolutions, aggregation scales, and prediction lead time. We use a
      state space reconstruction (SSR) approach to compare the predictability of
      mosquito population dynamics at weekly, biweekly, and monthly scales. We focus on
      the analysis of Aedes vexans and Culiseta melanura populations monitored in
      Brunswick County (North Carolina, USA) and find that prediction over a 7-d lead
      time is improved when daily observations are used, compared to the commonly used
      once-per-week sample. Our results demonstrate that daily observations of mosquito
      abundance contribute to improving mosquito predictability in two ways: (1) daily
      observations better capture fluctuations over short timescales, which are missed
      when sampling at coarser resolutions, and (2) the aggregation of daily abundance
      observations reduces the impact of noise, thereby increasing the predictability
      of mosquito population dynamics as the aggregation scale is increased. We show
      that the evaluation of population dynamical models based on observed and
      predicted abundance can lead to a spuriously high apparent performance, due to
      the high autocorrelation in the observations used to update the model state at
      each successive time step. We show that the comparison of predicted and observed
      population change, expressed through per capita growth rates, leads to a more
      informative performance measure.

PMID- 27865032
TI  - Intravoxel incoherent motion diffusion-weighted MRI of the abdomen: The effect of
      fitting algorithms on the accuracy and reliability of the parameters.
AB  - PURPOSE: To evaluate the influence of fitting methods on the accuracy and
      reliability of intravoxel incoherent motion (IVIM) parameters, with a particular
      emphasis on the constraint function. MATERIALS AND METHODS: Diffusion-weighted
      (DW) imaging data were analyzed using IVIM-based full-fitting (simultaneous fit
      of all parameters) and segmented-fitting (step-by-step fit of each parameter),
      each with and without the constraint function, to estimate the molecular
      diffusion coefficient (Dslow ), perfusion fraction (f), and flow-related
      diffusion coefficient (Dfast ). Computational simulations were performed at
      variable signal-to-noise ratios to evaluate the relative error (RE) and
      coefficient of variation (CV) of the estimated IVIM parameters. DW imaging of the
      abdomen was performed twice at 1.5 Tesla using nine b-values (0-900 s/mm2 ) in 12
      health volunteers (6 men and 6 women; mean age: 30 years). The measurement
      repeatability of IVIM parameters in the liver and the pancreas was evaluated
      using the within-subject coefficient of variation (w CV). RESULTS: In
      simulations, full-fitting without the constraint function yielded the largest RE
      (P < 0.001 for Dslow and f; P <= 0.044 for Dfast ) and CV (P <= 0.033 for Dslow
      and f; P <= 0.473 for Dfast ) for IVIM parameters among all four algorithms. In
      volunteer imaging, full-fitting without the constraint function also resulted in
      the poorest repeatability for Dslow (w CV, 17.12%-65.45%) and f (w CV, 19.35%
      42.84%) in the liver and pancreas, while the other algorithms had similar
      repeatability values (w CV, 4.05%-11.99% for Dslow and 9.65%-18.66% for f).
      Measurement repeatability of Dfast (w CV, 29.52%-85.01%) was the poorest among
      the IVIM parameters. CONCLUSION: For accurate and reliable measurement of IVIM
      parameters, segmented fitting or full-fitting with the constraint function should
      be used for IVIM-based analysis of DW imaging. LEVEL OF EVIDENCE: 3 Technical
      Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;45:1637-1647.

PMID- 27865033
TI  - Selective Production of Carbon Monoxide via Methane Oxychlorination over Vanadyl
      Pyrophosphate.
AB  - A catalytic process is demonstrated for the selective conversion of methane into
      carbon monoxide via oxychlorination chemistry. The process involves addition of
      HCl to a CH4 -O2 feed to facilitate C-H bond activation under mild conditions,
      leading to the formation of chloromethanes, CH3 Cl and CH2 Cl2 . The latter are
      oxidized in situ over the same catalyst, yielding CO and recycling HCl. A
      material exhibiting chlorine evolution by HCl oxidation, high activity to oxidize
      chloromethanes into CO, and no ability to oxidize CO, is therefore essential to
      accomplish this target. Following these design criteria, vanadyl pyrophosphate
      (VPO) was identified as an outstanding catalyst, exhibiting a CO yield up to
      approximately 35 % at 96 % selectivity and stable behavior. These findings
      constitute a basis for the development of a process enabling the on-site
      valorization of stranded natural-gas reserves using CO as a highly versatile
      platform molecule.

PMID- 27865035
TI  - The epidemiology of irritable bowel syndrome: Symptom development over a 3-year
      period in Denmark. A prospective, population-based cohort study.
AB  - BACKGROUND: We aimed to explore the natural history of irritable bowel syndrome
      (IBS) in Denmark over 3 years by studying development of IBS symptoms and
      associated factors. METHODS: A cohort study was carried out using a web panel
      representative of the Danish general population 18-50 years. The survey,
      including a questionnaire based on the Rome III criteria for IBS, was conducted
      in January 2010, January 2011, and March 2013. KEY RESULTS: The prevalence of IBS
      was 15.4% (920/5986). The incidence was 10.3%, and was three times higher for
      persons with unspecific gastrointestinal (GI) symptoms compared to asymptomatic
      persons. Of respondents with IBS symptoms in both 2010 and 2011, 69% (131/191)
      also reported symptoms of IBS in 2013, which was significantly more compared to
      respondents with IBS symptoms in 2010 reporting to be asymptomatic or having
      unspecific GI symptoms in 2011 (20% and 39%, respectively, P<.001). Being
      diagnosed with IBS predicted fulfilling the criteria for IBS 3 years later (OR:
      2.59, 95% CI: 1.11-6.10). Fulfilling criteria for IBS after 1 year also led to a
      high risk of IBS symptoms 3 years later in asymptomatic persons and persons with
      unspecific symptoms at baseline. CONCLUSIONS & INFERENCES: The vast majority of
      persons fulfilling criteria for IBS report GI symptoms after one and 3 years.
      Fulfilling IBS criteria after 1 year led to a high risk of reporting IBS symptoms
      after 3 years. In the general population having an IBS diagnosis predicts
      persistently fulfilling the Rome III criteria for IBS 3 years later.

PMID- 27865034
TI  - Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre-
      to post-liver transplant: a real-life strategy.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) re-infection following liver
      transplant (LT) is associated with reduced graft and patient survival. Before
      transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96%
      of those patients achieving viral suppression for at least 4 weeks before
      transplant. We evaluated whether a bridging SOF-regimen from pre- to post
      transplant is safe and effective to prevent HCV recurrence in those patients with
      less than 4 weeks of HCV-RNA undetectability at the time of transplant. METHODS:
      From July 2014 SOF/R was given in 233 waitlisted HCV cirrhotics with/without
      hepatocellular carcinoma (HCC) within an Italian Compassionate Program. One
      hundred patients were transplanted and 31 patients (31%) treated with SOF/R
      bridging therapy were studied. RESULTS: Liver transplant indication in bridge
      subgroup was HCC in 22 and decompensated cirrhosis in 9. HCV-genotype was 1/4 in
      18 patients. SOF 400 mg/day and R (median dosage 800 mg/day) were given for a
      median of 35 days before LT. At transplant time, 19 patients were still HCV-RNA
      positive (median HCV-RNA 58 IU/mL). One recipient had a virological breakthrough
      at week 4 post-transplant; one died, on treatment, 1-month post-transplant for
      sepsis and 29/31 achieved a 12-week sustained virological response (94%). Acute
      cellular rejection occurred in three recipients. On September 2016, 30 recipients
      (97%) were alive with a median follow-up of 18 months (range 13-25). CONCLUSIONS:
      In patients with suboptimal virological response at LT, a bridging SOF/R regimen
      helps avoiding post-transplant graft reinfection.

PMID- 27865036
TI  - Relationship between opioid treatment and rate of healing in chronic wounds.
AB  - Opioids are routinely used analgesics in patients with chronic wounds; however
      the impact of opioid exposure on wound healing is poorly understood. The purpose
      of this study was to investigate the association between opioid exposure and
      wound outcome in the Wound Etiology and Healing study. This longitudinal
      observational study was conducted on 450 subjects enrolled in the Wound Etiology
      and Healing biorepository. Data were collected prospectively including baseline
      characteristics, pain score, longitudinal opioid exposure, and total wound
      surface area (tWSA). Data were analyzed using static multivariate models, fixed
      effects mixed models, and time to event analysis. Using fixed-effects models,
      opioid dose was significantly associated with tWSA after accounting for the
      effects of pain score and baseline co-variates (p < 0.0001). For each 1-unit
      increase in ln(opioid dose + 1) the ln(tWSA + 1) increased by 0.16 units (95%
      confidence interval 0.13-0.19, p < 0.0001). Visits where opioids were present had
      ln(tWSA + 1) 0.48 units larger (95% confidence interval 0.38-0.58, p < 0.0001)
      than visits with no opioid exposure. Using time-to-event analysis, patients who
      never received opioids healed faster than those who received opioids (log-rank
      chi-square 11.00, p  = 0.0009). Using Cox regression analysis, patients with mean
      opioid dose >=10 mg were significantly less likely to heal than those with no
      opioid (HR 0.67 [0.49-0.91], p = 0.011) after adjusting for wound size. Patients
      with opioid dose >0 to <10 mg had a similar hazard of not healing as those with
      no opioid exposure (HR 0.88 [0.65-1.19], p = 0.40). In conclusion, opioid
      analgesics are commonly prescribed to patients with chronic wounds; however, the
      data presented suggest that opioid exposure is associated with reduced likelihood
      of healing in patients with chronic wounds. Whether this is a causal relationship
      will require further study.

PMID- 27865037
TI  - Short Enantioselective Total Synthesis of Tatanan A and 3-epi-Tatanan A Using
      Assembly-Line Synthesis.
AB  - Short and highly stereoselective total syntheses of the sesquilignan natural
      product tatanan A and its C3 epimer are described. An assembly-line synthesis
      approach, using iterative lithiation-borylation reactions, was applied to install
      the three contiguous stereocenters with high enantio- and diastereoselectivity.
      One of the stereocenters was installed using a configurationally labile lithiated
      primary benzyl benzoate, resulting in high levels of substrate-controlled
      (undesired) diastereoselectivity. However, reversal of selectivity was achieved
      by using a novel diastereoselective Matteson homologation. Stereospecific
      alkynylation of a hindered secondary benzylic boronic ester enabled completion of
      the synthesis in a total of eight steps.

PMID- 27865038
TI  - Modeling protein-protein and protein-peptide complexes: CAPRI 6th edition.
AB  - We present the sixth report evaluating the performance of methods for predicting
      the atomic resolution structures of protein complexes offered as targets to the
      community-wide initiative on the Critical Assessment of Predicted Interactions
      (CAPRI). The evaluation is based on a total of 20,670 predicted models for 8
      protein-peptide complexes, a novel category of targets in CAPRI, and 12 protein
      protein targets in CAPRI prediction Rounds held during the years 2013-2016. For
      two of the protein-protein targets, the focus was on the prediction of side-chain
      conformation and positions of interfacial water molecules. Seven of the protein
      protein targets were particularly challenging owing to their multicomponent
      nature, to conformational changes at the binding site, or to a combination of
      both. Encouragingly, the very large multiprotein complex with the nucleosome was
      correctly predicted, and correct models were submitted for the protein-peptide
      targets, but not for some of the challenging protein-protein targets. Models of
      acceptable quality or better were obtained for 14 of the 20 targets, including
      medium quality models for 13 targets and high quality models for 8 targets,
      indicating tangible progress of present-day computational methods in modeling
      protein complexes with increased accuracy. Our evaluation suggests that the
      progress stems from better integration of different modeling tools with docking
      procedures, as well as the use of more sophisticated evolutionary information to
      score models. Nonetheless, adequate modeling of conformational flexibility in
      interacting proteins remains an important area with a crucial need for
      improvement. Proteins 2017; 85:359-377. (c) 2016 Wiley Periodicals, Inc.

PMID- 27865039
TI  - Alcohol consumption during adolescence is associated with reduced grey matter
      volumes.
AB  - BACKGROUND AND AIMS: Cognitive impairment has been associated with excessive
      alcohol use, but its neural basis is poorly understood. Chronic excessive alcohol
      use in adolescence may lead to neuronal loss and volumetric changes in the brain.
      Our objective was to compare the grey matter volumes of heavy- and light-drinking
      adolescents. DESIGN: This was a longitudinal study: heavy-drinking adolescents
      without an alcohol use disorder and their light-drinking controls were followed
      up for 10 years using questionnaires at three time-points. Magnetic resonance
      imaging was conducted at the last time-point. SETTING: The area near Kuopio
      University Hospital, Finland. PARTICIPANTS: The 62 participants were aged 22-28
      years and included 35 alcohol users and 27 controls who had been followed-up for
      approximately 10 years. MEASUREMENTS: Alcohol use was measured by the Alcohol Use
      Disorders Identification Test (AUDIT)-C at three time-points during 10 years.
      Participants were selected based on their AUDIT-C score. Magnetic resonance
      imaging was conducted at the last time-point. Grey matter volume was determined
      and compared between heavy- and light-drinking groups using voxel-based
      morphometry on three-dimensional T1-weighted magnetic resonance images using
      predefined regions of interest and a threshold of P < 0.05, with small volume
      correction applied on cluster level. FINDINGS: Grey matter volumes were
      significantly smaller among heavy-drinking participants in the bilateral anterior
      cingulate cortex, right orbitofrontal and frontopolar cortex, right superior
      temporal gyrus and right insular cortex compared to the control group (P < 0.05,
      family-wise error-corrected cluster level). CONCLUSIONS: Excessive alcohol use
      during adolescence appears to be associated with an abnormal development of the
      brain grey matter. Moreover, the structural changes detected in the insula of
      alcohol users may reflect a reduced sensitivity to alcohol's negative subjective
      effects.

PMID- 27865041
TI  - Self-Powered Multimodal Temperature and Force Sensor Based-On a Liquid Droplet.
AB  - Herein we report a self-powered multimodal temperature and force sensor based on
      the reverse electrowetting effect and the thermogalvanic effect in a liquid
      droplet. The deformation of the droplet and the temperature difference across the
      droplet can induce an alternating pulse voltage and a direct voltage,
      respectively, which is easy to separate/analyze and can be utilized to sense the
      external force and temperature simultaneously. In addition, an integral display
      system that can derive information from external temperature/force concurrently
      is constructed. Combined with advantages of excellent sensing properties and a
      simple structure, the droplet sensor has promising applications in a wide range
      of intelligent electronics.

PMID- 27865042
TI  - Dopant-Catalyzed Singlet Exciton Fission.
AB  - In acene-based molecular crystals, singlet exciton fission occurs through
      superexchange mediated by two virtual charge-transfer states. Hence, it is
      sensitive to their energies, which depend on the local environment. The crucial
      point is the balance between the charge-quadrupole interactions within the pair
      of molecules directly involved in the process and those with the surrounding
      crystal matrix, which are governed by local symmetry and may be influenced by
      breaking this symmetry. This happens, for example, in the vicinity of a vacancy
      or an impurity and in the latter case is complemented by polarization energy and
      potentially by dipolar contributions. Our model calculations indicate that the
      superexchange coupling is sensitive enough to these factors to enable fission to
      be catalyzed by judiciously designed dopant molecules. In favorable cases,
      dipolar dopants are expected to increase the fission rate by an order of
      magnitude.

PMID- 27865040
TI  - Psychological Outcomes of Living Liver Donors From a Multicenter Prospective
      Study: Results From the Adult-to-Adult Living Donor Liver Transplantation Cohort
      Study2 (A2ALL-2).
AB  - Although single-center and cross-sectional studies have suggested a modest impact
      of liver donation on donor psychological well-being, few studies have assessed
      these outcomes prospectively among a large cohort. We conducted one of the
      largest, prospective, multicenter studies of psychological outcomes in living
      liver donors within the Adult-to-Adult Living Donor Liver Transplantation Cohort
      Study2 (A2ALL-2) consortium. In total, 271 (91%) of 297 eligible donors were
      interviewed at least once before donation and at 3, 6, 12, and 24 mo after
      donation using validated measures. We found that living liver donors reported low
      rates of major depressive (0-3%), alcohol abuse (2-5%), and anxiety syndromes (2
      3%) at any given assessment in their first 2 years after donation. Between 4.7%
      and 9.6% of donors reported impaired mental well-being at various time points. We
      identified significant predictors for donors' perceptions of being better people
      and experiencing psychological growth following donation, including age, sex,
      relationship to recipient, ambivalence and motivation regarding donation, and
      feeling that donation would make life more worthwhile. Our results highlight the
      need for close psychosocial monitoring for those donors whose recipients died
      (n=27); some of those donors experienced guilt and concerns about responsibility.
      Careful screening and targeted, data-driven follow-up hold promise for optimizing
      psychological outcomes following this procedure for potentially vulnerable
      donors.

PMID- 27865043
TI  - Self-Sorting of Two Hydrocarbon Receptors with One Carbonaceous Ligand.
AB  - Non-directional van der Waals forces in biological and synthetic supramolecular
      systems play important roles in molecular assembly, particularly in determining
      the distances of the interacting species. The van der Waals forces are normally
      used in combination with other directional forces and are considered to play a
      secondary role in achieving specificity and fidelity in molecular recognition.
      Using an ideal supramolecular system consisting solely of hydrogen and carbon
      atoms, we found that the van der Waals interactions enable the high-fidelity
      sorting of two homomeric receptors during ligand-induced assembly. The self
      sorting occurred in a narcissistic manner by repulsion of a competing
      diastereoisomeric receptor from the assembly. The structure-sorting relationship
      study with enantiomers further revealed the dominant role of the van der Waals
      forces in shape recognition for high-fidelity self-sorting.

PMID- 27865044
TI  - Cyclo(RGD)-Decorated Reduction-Responsive Nanogels Mediate Targeted Chemotherapy
      of Integrin Overexpressing Human Glioblastoma In Vivo.
AB  - Cyclo(Arg-Gly-Asp) peptide (cRGD) decorated disulfide (SS) containing poly(vinyl
      alcohol) nanogels (cRGD-SS-NGs) with an average diameter of 142 nm prepared by
      inverse nanoprecipitation, "click" reaction, and cRGD conjugation are developed
      for targeted treatment of integrin overexpressing human glioblastoma in vivo.
      Doxorubicin (DOX) release from cRGD-SS-NGs is highly inhibited under
      physiological conditions, while accelerated at endosomal pH and in response to
      cytoplasmic concentration of glutathione. Confocal microscopy shows that cRGD-SS
      NGs facilitate the cellular uptake and intracellular DOX release in alphav beta3
      integrin overexpressing human glioblastoma U87-MG cells. DOX-loaded cRGD-SS-NGs
      present much better killing activity toward U87-MG cells than that for
      nontargeted nanogels determined by MTT assay. The in vivo imaging and
      biodistribution studies reveal that DOX-loaded cRGD-SS-NGs have a much better
      tumor targetability toward human U87-MG glioblastoma xenograft in nude mice. Also
      the tumor growth is effectively inhibited by treatment with DOX-loaded cRGD-SS
      NGs, while continuous tumor growth is observed for mice treated with nondecorated
      nanogels as well as free DOX. Furthermore, the treatment with DOX-loaded cRGD-SS
      NGs has much fewer side effects, rendering these nanogels as a new platform for
      cancer chemotherapy in vivo.

PMID- 27865046
TI  - Functional Proteins from Short Peptides: Dayhoff's Hypothesis Turns 50.
AB  - First and foremost: Margaret Dayhoff's 1966 hypothesis on the origin of proteins
      is now an accepted model for the emergence of large, globular, functional
      proteins from short, simple peptides. However, the fundamental question of how
      the first protein(s) emerged still stands. The tools and hypotheses pioneered by
      Dayhoff, and the over 65 million protein sequences and 12 000 structures known
      today, enable those who follow in her footsteps to address this question.

PMID- 27865047
TI  - Carbon lost and carbon gained: a study of vegetation and carbon trade-offs among
      diverse land uses in Phoenix, Arizona.
AB  - Human modification and management of urban landscapes drastically alters
      vegetation and soils, thereby altering carbon (C) storage and rates of net
      primary productivity (NPP). Complex social and ecological processes drive
      vegetation cover in cities, leading to heterogeneity in C dynamics depending on
      regional climate, land use, and land cover. Recent work has demonstrated
      homogenization in ecological processes within human-dominated landscapes (the
      urban convergence hypothesis) in soils and biotic communities. However, a lack of
      information on vegetation in arid land cities has hindered an understanding of
      potential C storage and NPP convergence across a diversity of ecosystem types. We
      estimated C storage and NPP of trees and shrubs for six different land-use types
      in the arid metropolis of Phoenix, Arizona, USA, and compared those results to
      native desert ecosystems, as well as other urban and natural systems around the
      world. Results from Phoenix do not support the convergence hypothesis. In
      particular, C storage in urban trees and shrubs was 42% of that found in desert
      vegetation, while NPP was only 20% of the total NPP estimated for comparable
      natural ecosystems. Furthermore, the overall estimates of C storage and NPP
      associated with urban trees in the CAP ecosystem were much lower (8-63%) than the
      other cities included in this analysis. We also found that C storage (175.25
      388.94 g/m2 ) and NPP (8.07-15.99 g.m-2 .yr-1 ) were dominated by trees in the
      urban residential land uses, while in the desert, shrubs were the primary source
      for pools (183.65 g/m2 ) and fluxes (6.51 g.m-2 .yr-1 ). These results indicate a
      trade-off between shrubs and trees in arid ecosystems, with shrubs playing a
      major role in overall C storage and NPP in deserts and trees serving as the
      dominant C pool in cities. Our research supports current literature that calls
      for the development of spatially explicit and standardized methods for analyzing
      C dynamics associated with vegetation in urbanizing areas.

PMID- 27865045
TI  - High KRT8 expression promotes tumor progression and metastasis of gastric cancer.
AB  - Keratin8 (KRT8) is the major component of the intermediate filament cytoskeleton
      and predominantly expressed in simple epithelial tissues. Aberrant expression of
      KRT8 is associated with multiple tumor progression and metastasis. However, the
      role of KRT8 in gastric cancer (GC) remains unclear. In this study, KRT8
      expression was investigated and it was found to be upregulated along with human
      GC progression and metastasis at both mRNA and protein levels in human gastric
      cancer tissues. In addition, KRT8 overexpression enhanced the proliferation and
      migration of human gastric cancer cells, whereas the knock-down of KRT8 by siRNA
      only inhibited migration of human gastric cancer cells. Integrinbeta1-FAK-induced
      epithelial-mesenchymal-transition (EMT) only existed in the high KRT8 cells.
      Furthermore, KRT8 overexpression led to increase in p-smad2/3 levels and TGFbeta
      dependent signaling events. KRT8 expression in GC was related to tumor clinical
      stage and worse survival. Kaplan-Meier analysis proved that KRT8 was associated
      with overall survival of patients with GC that patients with high KRT8 expression
      tend to have unfavorable outcome. Moreover, Cox's proportional hazards analysis
      showed that high KRT8 expression was a prognostic marker of poor outcome. These
      results provided that KRT8 expression may therefore be a biomarker or potential
      therapeutic target to identify patients with worse survival.

PMID- 27865048
TI  - Neuroligin 2 nonsense variant associated with anxiety, autism, intellectual
      disability, hyperphagia, and obesity.
AB  - Neuroligins are post-synaptic, cellular adhesion molecules implicated in synaptic
      formation and function. NLGN2 is strongly linked to inhibitory, GABAergic
      signaling and is crucial for maintaining the excitation-inhibition balance in the
      brain. Disruption of the excitation-inhibition balance is associated with
      neuropsychiatric disease. In animal models, altered NLGN2 expression causes
      anxiety, developmental delay, motor discoordination, social impairment,
      aggression, and sensory processing defects. In humans, mutations in NLGN3 and
      NLGN4 are linked to autism and schizophrenia; NLGN2 missense variants are
      implicated in schizophrenia. Copy number variants encompassing NLGN2 on 17p13.1
      are associated with autism, intellectual disability, metabolic syndrome,
      diabetes, and dysmorphic features, but an isolated NLGN2 nonsense variant has not
      yet been described in humans. Here, we describe a 15-year-old male with severe
      anxiety, obsessive-compulsive behaviors, developmental delay, autism, obesity,
      macrocephaly, and some dysmorphic features. Exome sequencing identified a
      heterozygous, de novo, c.441C>A p.(Tyr147Ter) variant in NLGN2 that is predicted
      to cause loss of normal protein function. This is the first report of an NLGN2
      nonsense variant in humans, adding to the accumulating evidence that links
      synaptic proteins with a spectrum of neurodevelopmental phenotypes. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27865049
TI  - Hollow Nanotubes of N-Doped Carbon on CoS.
AB  - Low-cost, single-step synthesis of hollow nanotubes of N-doped carbon deposited
      on CoS is enabled by the simultaneous use of three functionalities of
      polyacrylonitrite (PAN) nanofibers: 1) a substrate for loading active materials,
      2) a sacrificial template for creating hollow tubular structures, and 3) a
      precursor for in situ nitrogen doping. The N-doped carbon in hollow tubes of CoS
      provides a high-capacity anode of long cycle life for a rechargeable Li-ion or Na
      ion battery cell that undergoes the conversion reaction 2 A+ +2 e- +CoS ->Co+A2 S
      with A=Li or Na.

PMID- 27865051
TI  - The Role of Entropy in Nanoparticle Agglomeration.
AB  - Agglomeration processes in non-interacting particle systems can be understood
      from a thermodynamic point of view. If the enthalpy of agglomeration is
      negligible, the distribution of agglomeration states adopts the state of highest
      entropy. Herein, we provide the exact analytical solution to the mole fractions
      of agglomerates comprising i monomers, xi =2-i .

PMID- 27865050
TI  - NMR Spectroscopic Assignment of Backbone and Side-Chain Protons in Fully
      Protonated Proteins: Microcrystals, Sedimented Assemblies, and Amyloid Fibrils.
AB  - We demonstrate sensitive detection of alpha protons of fully protonated proteins
      by solid-state NMR spectroscopy with 100-111 kHz magic-angle spinning (MAS). The
      excellent resolution in the Calpha-Halpha plane is demonstrated for 5 proteins,
      including microcrystals, a sedimented complex, a capsid and amyloid fibrils. A
      set of 3D spectra based on a Calpha-Halpha detection block was developed and
      applied for the sequence-specific backbone and aliphatic side-chain resonance
      assignment using only 500 MUg of sample. These developments accelerate structural
      studies of biomolecular assemblies available in submilligram quantities without
      the need of protein deuteration.

PMID- 27865052
TI  - Retention in care and reasons for discontinuation of lifelong antiretroviral
      therapy in a cohort of Cameroonian pregnant and breastfeeding HIV-positive women
      initiating 'Option B+' in the South West Region.
AB  - OBJECTIVE: To assess linkage and retention in care along the PMTCT cascade in HIV
      positive pregnant and breastfeeding women initiating Option B+ in Cameroon.
      METHODS: We prospectively determined uptake of HIV testing and counselling (HTC),
      uptake of ART and retention in care after Option B+ initiation between October
      2013 and December 2014 in pregnant and breastfeeding women from five sites within
      the Kumba Health District. Retention in care was assessed over at least 12 months
      follow-up and estimated by Kaplan-Meier analysis. During follow-up, tracing
      outcomes and reasons for discontinuing treatment were documented. RESULTS: The
      uptake of HTC of 5813 women with unknown HIV status was 98.5%, 251 (4.4%) were
      newly diagnosed HIV positive, and ART uptake in women eligible to start Option B+
      was 96.8%. We enrolled 268 women initiating lifelong ART in the follow-up.
      Overall, 65 (24.3%) discontinued treatment, either defined by loss to follow-up
      (44.6%) or actively stopped treatment (55.8%). Retention in care was 88.0% and
      81.1% at 6 and 12 months, respectively. Discontinuation was significantly
      associated in multivariate analysis with small sites and high staff turnover [aOR
      2.5 (95% CI 1.6, 3.9), P < 0.001]. Main reasons for stopping treatment were HIV
      status denial and stigma (52.8%), religious reasons (25.0%) and lack of transport
      fare (11.1%). CONCLUSION: We observed good uptake of HTC, ART and retention in
      care, which declined over time. Discontinuation of Option B+ was highest at small
      sites with a high staff turnover. Improved staffing, adequate task shifting and
      community interventions to track defaulters including reducing stigma and
      religious beliefs may improve Option B+ retention.

PMID- 27865053
TI  - Neural progenitor cells and their role in the development and evolutionary
      expansion of the neocortex.
AB  - The evolutionary expansion of the mammalian brain, notably the neocortex,
      provides a platform for the higher cognitive abilities that characterize humans.
      Cortical expansion is accompanied by increased folding of the pial surface, which
      gives rise to a gyrencephalic (folded) rather than lissencephalic (unfolded)
      neocortex. This expansion reflects the prolonged and increased proliferation of
      neural stem and progenitor cells (NPCs). Distinct classes of NPCs can be
      distinguished based on either cell biological criteria (apical progenitors [APs],
      basal progenitors [BPs]) or lineage (primary progenitors and secondary
      progenitors). Cortical expansion in development and evolution is linked to an
      increased abundance and proliferative capacity of BPs, notably basal radial glial
      cells, a recently characterized type of secondary progenitor derived from apical
      radial glial cells, the primary progenitors. To gain insight into the molecular
      basis underlying the prolonged and increased proliferation of NPCs and in
      particular BPs, comparative genomic and transcriptomic approaches, mostly for
      human versus mouse, have been employed and applied to specific NPC types and
      subpopulations. These have revealed two principal sets of molecular changes. One
      concerns differences in the expression of common genes between species with
      different degrees of cortical expansion. The other comprises human-specific genes
      or genomic regulatory sequences. Various systems that allow functional testing of
      these genomic and gene expression differences between species have emerged,
      including transient and stable transgenesis, genome editing, cerebral organoids,
      and organotypic slice cultures. These provide future avenues for uncovering the
      molecular basis of cortical expansion. WIREs Dev Biol 2017, 6:e256. doi:
      10.1002/wdev.256 For further resources related to this article, please visit the
      WIREs website.

PMID- 27865055
TI  - Relationship between healthy lifestyle behaviors and health locus of control and
      health-specific self-efficacy in university students.
AB  - AIM: To investigate the relationship between the healthy lifestyle behaviors and
      the health locus of control and health-specific self-efficacy in university
      students. METHODS: The study included 572 undergraduate students of a university
      in the central Anatolia region of Turkey. The data were collected with the
      General Characteristics Form, the Health-Promoting Lifestyle Profile II, the
      Multidimensional Health Locus of Control Scale, and the Perceived Health
      Competence Scale and investigated with the structural equation model. RESULTS:
      Health-specific self-efficacy was an important predictor of healthy lifestyle
      behaviors. The Internal health locus of control influenced the healthy lifestyle
      behaviors through health-specific self-efficacy. The other dimension was the
      Powerful Others health locus of control that affected healthy lifestyle
      behaviors, both directly and indirectly, through health-specific self-efficacy.
      There was a chance that the health locus of control had a negative effect on
      healthy lifestyle behaviors through self-efficacy. CONCLUSION: Health-specific
      self-efficacy is an important prerequisite for changes in healthy lifestyle
      behaviors, which supports Pender's model. The subscales of the health locus of
      control vary in their effects on healthy lifestyle behaviors, which partly
      supports Pender's model. Nurses, by using this model, can examine ways of
      improving these cognitive-perceptual factors and implement health education
      programs that are directed towards improving them in young persons.

PMID- 27865054
TI  - Biodistribution of Carbon Nanotubes in Animal Models.
AB  - The many interesting physical and chemical properties of carbon nanotubes (CNT)
      make it one of the most commercially attractive materials in the era of
      nanotechnology. Here, we review the recent publications on in vivo
      biodistribution of pristine and functionalized forms of single-walled and multi
      walled CNT. Pristine CNT remain in the lung for months or even years after
      pulmonary deposition. If cleared, the majority of CNT move to the
      gastrointestinal (GI) tract via the mucociliary escalator. However, there appears
      to be no uptake of CNT from the GI tract, with a possible exception of the
      smallest functionalized SWCNT. Importantly, a significant fraction of CNT
      translocate from the alveolar space to the near pulmonary region including lymph
      nodes, subpleura and pleura (<7% of the pulmonary deposited dose) and to distal
      organs including liver, spleen and bone marrow (~1%). These results clearly
      demonstrate the main sites of long-term CNT accumulation, which also includes
      pleura, a major site for fibre-induced pulmonary diseases. Studies on intravenous
      injection show that CNT in blood circulation are cleared relatively fast with a
      half-life of minutes or hours. The major target organs were the same as
      identified after pulmonary exposure with the exception of urine excretion of
      especially functionalized SWCNT and accumulation in lung tissue. Overall, there
      is evidence that CNT will primarily be distributed to the liver where they appear
      to be present at least one year after exposure.

PMID- 27865056
TI  - The caspase-activated DNase: apoptosis and beyond.
AB  - Organismal development and function requires multiple and accurate signal
      transduction pathways to ensure that proper balance between cell proliferation,
      differentiation, inactivation, and death is achieved. Cell death via apoptotic
      caspase signal transduction is extensively characterized and integral to this
      balance. Importantly, the view of apoptotic signal transduction has expanded over
      the previous decades. Subapoptotic caspase signaling has surfaced as mechanism
      that can promote the adoption of a range of cellular fates. An emerging mechanism
      of subapoptotic caspase signaling is the activation of the caspase-activated
      DNase (CAD) through controlled cleavage of the inhibitor of CAD (ICAD). CAD
      induced DNA breaks incite a DNA damage response, frequently invoking p53
      signaling, that transduces a change in cell fate. Cell differentiation and
      senescence are fates demonstrated to arise from CAD-induced DNA breaks.
      Furthermore, an apparent consequence of CAD activity is also emerging, as a
      potential source of oncogenic mutations. This review will discuss the mechanisms
      underlying CAD-induced DNA breaks and highlight how CAD activity promotes diverse
      cell fates.

PMID- 27865057
TI  - Insulin resistance and its association with catch-up growth in Chinese children
      born small for gestational age.
AB  - OBJECTIVE: To assess insulin resistance and beta-cell function from birth to age
      4 years and to examine their associations with catch-up growth (CUG) in Chinese
      small-for-gestational-age (SGA) children. METHODS: Weight and height were
      measured yearly from birth to age 4 years, and transformed into age- and gender
      adjusted SD scores. Fasting serum insulin and glucose were measured, and fasting
      insulin resistance and beta-cell function were estimated using the homeostasis
      model assessment (HOMA). RESULTS: The mean HOMA-IR of the SGA group was
      significantly lower than that of the appropriate-for-gestational-age (AGA) group
      at ages 2 and 3 years old, and the mean HOMA% of the SGA group was significantly
      lower than that of the AGA group at age 4 years old. At 4 years of age, HOMA for
      insulin resistance was positively correlated with the height gain and SD of
      height gain between 0 and 5 months, and HOMA% was positively correlated with the
      weight gain and SD of weight gain between 6 and 12 months in SGA children.
      CONCLUSIONS: SGA children with CUG show a greater propensity to develop insulin
      resistance than AGA children between ages 2 and 4 years old. HOMA parameters are
      related to CUG in the first year of life.

PMID- 27865058
TI  - Ischemia modified albumin concentrations in patients with rheumatoid arthritis.

PMID- 27865059
TI  - Synergistic Effect of Cobalt and Iron in Layered Double Hydroxide Catalysts for
      the Oxygen Evolution Reaction.
AB  - Co-based layered double hydroxide (LDH) catalysts with Fe and Al contents in the
      range of 15 to 45 at % were synthesized by an efficient coprecipitation method.
      In these catalysts, Fe3+ or Al3+ ions play an essential role as trivalent species
      to stabilize the LDH structure. The obtained catalysts were characterized by a
      comprehensive combination of surface- and bulk-sensitive techniques and were
      evaluated for the oxygen evolution reaction (OER) on rotating disk electrodes.
      The OER activity decreased upon increasing the Al content for the Co- and Al
      based LDH catalysts, whereas a synergistic effect in Co- and Fe-based LDHs was
      observed, which resulted in an optimal Fe content of 35 at %. This catalyst was
      spray-coated on Ni foam electrodes and showed very good stability in a flow
      through cell with a potential of approximately 1.53 V at 10 mA cm-2 in 1 m KOH
      for at least 48 h.

PMID- 27865060
TI  - Reducing variation in feeding newborns with congenital heart disease.
AB  - OBJECTIVE: Enteral feeding is associated with decreased infection rates,
      decreased mechanical ventilation, decreased hospital length of stay, and improved
      wound healing. Enteral feeding difficulties are common in congenital heart
      disease. Our objective was to develop experience-based newborn feeding guidelines
      for the initiation and advancement of enteral feeding in the cardiothoracic
      intensive care unit. DESIGN: This is a retrospective analysis of a quality
      improvement project. SETTING: This quality improvement project was performed in a
      cardiothoracic intensive care unit. PATIENTS: Newborns admitted to the
      cardiothoracic intensive care unit for cardiac surgery from January 2011 to May
      2015 were retrospectively reviewed. INTERVENTION: Newborn feeding guidelines for
      the initiation and advancement of enteral feeding were implemented in January
      2012. OUTCOME MEASURES: Guideline compliance and clinical variables before and
      after guideline implementation were reviewed. RESULTS: Compliance with the
      guidelines increased from 83% in 2012 to 100% in the first two quarters of 2015.
      Preguidelines (January 2011-December 2011): 45 newborns underwent cardiac
      surgery; 8 deaths prior to discharge; 1 patient discharged from NICU, therefore,
      N = 36. Postguidelines (January 2012-May 2015): 131 newborns with 12 deaths, 12
      admitted from home, 8 in the NICU, 3 on the floor preop, and 3 back transferred,
      therefore, N = 93. No difference in feeding preop (post 75% vs pre 69%; P = .5)
      or full po feeds at discharge (post 78% vs pre 89%; P = .2). Mesenteric ischemia
      was not statistically different postguidelines (post 6% vs pre 14%; P = .14).
      Length of hospital stay decreased postguidelines (post 27 + 17 d vs pre 34 + 42
      d; P < .001). CONCLUSIONS: Implementation of experience-based newborn feeding
      guidelines for initiation and advancement of enteral feeding in the
      cardiothoracic intensive care unit was successful in reducing practice variation
      supported by increasing guideline compliance. Percentage of patient's full oral
      feeding at discharge did not change. Length of hospital stay was reduced although
      cannot be fully attributed to feeding guideline implementation.

PMID- 27865061
TI  - Setting spatial conservation priorities despite incomplete data for
      characterizing metapopulations.
AB  - Management of spatially structured species poses unique challenges. Despite a
      strong theoretical foundation, practitioners rarely have sufficient empirical
      data to evaluate how populations interact. Rather, assumptions about connectivity
      and source-sink dynamics are often based on incomplete, extrapolated, or modeled
      data, if such interactions are even considered at all. Therefore, it has been
      difficult to evaluate whether spatially structured species are meeting
      conservation goals. We evaluated how estimated metapopulation structure responded
      to estimates of population sizes and dispersal probabilities and to the set of
      populations included. We then compared outcomes of alternative management
      strategies that target conservation of metapopulation processes. We illustrated
      these concepts for Chinook salmon (Oncorhynchus tshawytscha) in the Snake River,
      USA. Our description of spatial structure for this metapopulation was consistent
      with previous characterizations. We found substantial differences in estimated
      metapopulation structure when we had incomplete information about all populations
      and when we used different sources of data (three empirical, two modeled) to
      estimate dispersal, whereas responses to population size estimates were more
      consistent. Together, these findings suggest that monitoring efforts should
      target all populations occasionally and populations that play key roles
      frequently and that multiple types of data should be collected when feasible.
      When empirical data are incomplete or of uneven quality, analyses using estimates
      produced from an ensemble of available datasets can help conservation planners
      and managers weigh near-term options. Doing so, we found trade-offs in
      connectivity and source dominance in metapopulation-level responses to
      alternative management strategies that suggest which types of approaches may be
      inherently less risky.

PMID- 27865062
TI  - Endoscopic nasopharyngectomy in recurrent nasopharyngeal carcinoma: a case
      series, literature review, and pooled analysis.
AB  - BACKGROUND: To critically evaluate the use of endoscopic nasopharyngectomy in the
      treatment of recurrent nasopharyngeal carcinoma (NPC) through a case series,
      systematic literature review, and pooled analysis. METHODS: A case series of 18
      patients combined with systematic literature review and pooled analysis of
      PubMed, Web of Science, and Scopus search, identifying 576 papers. After
      excluding 307 papers as search engine duplicates, only 16 of the remaining papers
      had adequate patient data to be included. RESULTS: Our case series of 18 patients
      had a 2-year disease-free survival (DFS) and overall survival (OS) of 90.0% and
      100%, respectively. The pooled analysis of 300 patients that had an endoscopic
      resection of recurrent NPC showed recurrence-free survival and overall survival
      were 85.8% and 82.9%, respectively. Most, 56.1%, were recurrent T1 lesions.
      Resection margins were negative in 90.2% of patients. Local recurrence occurred
      in 20.1% of patients. Major complications occurred in 13.6% of patients. The mean
      hospital stay was 5.8 days, the mean operating time was 228.3 minutes, and the
      mean operative blood loss was 163 mL. CONCLUSION: Endoscopic resection of
      recurrent NPC occurs with low surgical morbidity. However, further long-term
      evaluation with longer follow-up data is needed to evaluate if the survival data
      is comparable or better than open approaches.

PMID- 27865063
TI  - Face, content, and construct validation of a low-cost, non-biologic, sinus
      surgery task trainer and knowledge-based curriculum.
AB  - BACKGROUND: The purpose of this study was to evaluate face and content validity
      of a low-cost, low-technology, non-biologic endoscopic sinus surgery (ESS) task
      trainer and knowledge-based curriculum followed by construct validation of the
      task trainer. METHODS: A sinus surgery task trainer and curriculum were
      developed. Attending otolaryngologists were surveyed regarding the utility of the
      task trainer and curriculum. A cross-sectional construct validation study was
      performed including medical students, residents, and attending otolaryngologists.
      Nine tasks were performed on the task trainer and graded using a global rating
      scale (GRS). Predictors of task trainer performance were evaluated, and spatial
      performance was measured. Regression analyses were performed to assess main
      associations. RESULTS: All attending physicians (n = 7) agreed that the task
      trainer accelerates the learning curve and incorporates essential ESS techniques
      and that the knowledge-based curriculum describes anatomical and technical
      knowledge germane to ESS. Twelve medical students, 9 otolaryngology residents,
      and 5 attending otolaryngologists completed task trainer testing. GRS score
      varied by level of training after adjusting for potential confounders (slope =
      2.63; p = 0.001). There was evidence of an association between a history of video
      gaming (slope = 1.33; p = 0.077), sports experience (slope = 2.08; p = 0.033),
      and sinus surgery simulation (slope = 2.72; p = 0.023) with GRS score, although
      not statistically significant. CONCLUSION: This study demonstrated validity of a
      knowledge-based sinus surgery curriculum and low-cost, sinus task trainer
      supporting use in early training. Participants with prior video gaming, sports
      participation, and sinus surgery simulation experience perform better at baseline
      on the task trainer.

PMID- 27865064
TI  - Estimating vaccine effectiveness in preventing laboratory-confirmed influenza in
      outpatient settings in South Africa, 2015.
AB  - Trivalent seasonal influenza vaccine effectiveness during the 2015 season in
      South Africa was assessed using a test-negative case control study design.
      Influenza A(H1N1)pdm09 was the dominant circulating strain. Overall influenza
      vaccine coverage was 3.2% (29/899). The vaccine effectiveness estimate, against
      any influenza virus infection, adjusted for age, underlying conditions and timing
      within season was 46.2% (95% CI: -23.5 to 76.5), and 53.6% (95% CI: -62.6 to
      80.3) against influenza A(H1N1)pdm09.

PMID- 27865065
TI  - How do we recognize the child with OSAS?
AB  - Obstructive sleep-disordered breathing includes a spectrum of clinical entities
      with variable severity ranging from primary snoring to obstructive sleep apnea
      syndrome (OSAS). The clinical suspicion for OSAS is most often raised by parental
      report of specific symptoms and/or abnormalities identified by the physical
      examination which predispose to upper airway obstruction (e.g., adenotonsillar
      hypertrophy, obesity, craniofacial abnormalities, neuromuscular disorders).
      Symptoms and signs of OSAS are classified into those directly related to the
      intermittent pharyngeal airway obstruction (e.g., parental report of snoring,
      apneic events) and into morbidity resulting from the upper airway obstruction
      (e.g., increased daytime sleepiness, hyperactivity, poor school performance,
      inadequate somatic growth rate or enuresis). History of premature birth and a
      family history of OSAS as well as obesity and African American ethnicity are
      associated with increased risk of sleep-disordered breathing in childhood.
      Polysomnography is the gold standard method for the diagnosis of OSAS but may not
      be always feasible, especially in low-income countries or non-tertiary hospitals.
      Nocturnal oximetry and/or sleep questionnaires may be used to identify the child
      at high risk of OSAS when polysomnography is not an option. Endoscopy and MRI of
      the upper airway may help to identify the level(s) of upper airway obstruction
      and to evaluate the dynamic mechanics of the upper airway, especially in children
      with combined abnormalities. Pediatr Pulmonol. 2017;52:260-271. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27865067
TI  - Laminin-modified and aligned poly(3-hydroxybutyrate-co-3
      hydroxyvalerate)/polyethylene oxide nanofibrous nerve conduits promote peripheral
      nerve regeneration.
AB  - Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) has received much attention
      for its biodegradability and biocompatibility, characteristics that are required
      in tissue engineering. In this study, polyethylene oxide (PEO)-incorporated PHBV
      nanofibres with random or aligned orientation were obtained by electrospinning.
      For further use in vivo, the nanofibre films were made into nerve conduits after
      treatment with NH3 plasma, which could improve the hydrophilicity of inner
      surfaces of nerve conduits and then facilitate laminin adsorption via
      electrostatic interaction for promoting cell adhesion and proliferation.
      Morphology of the surfaces of modified PHBV/PEO nanofibrous scaffolds were
      examined by scanning electron microscopy. Schwann cell viability assay was
      conducted and the results confirmed that the functionalized nanofibres were
      favourable for cell growth. Morphology of Schwann cells cultured on scaffolds
      showed that aligned nanofibrous scaffolds provided topographical guidance for
      cell orientation and elongation. Furthermore, three-dimensional PHBV/PEO nerve
      conduits made from aligned and random-oriented nanofibres were implanted into 12
      mm transected sciatic nerve rat model and subsequent analysis were conducted at 1
      and 2 months postsurgery. The above functionalized PHBV/PEO scaffolds provide a
      novel and promising platform for peripheral nerve regeneration. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27865066
TI  - Newly synthesized cAMP is integrated at a membrane protein complex signalosome to
      ensure receptor response specificity.
AB  - Spatiotemporal regulation of cAMP within the cell is required to achieve receptor
      specific responses. The mechanism through which the cell selects a specific
      response to newly synthesized cAMP is not fully understood. In hepatocyte plasma
      membranes, we identified two functional and independent cAMP-responsive signaling
      protein macrocomplexes that produce, use, degrade, and regulate their own
      nondiffusible (sequestered) cAMP pool to achieve their specific responses. Each
      complex responds to the stimulation of an adenosine G protein-coupled receptor
      (Ado-GPCR), bound to either A2A or A2B , but not simultaneously to both. Each
      isoprotein involved in each signaling cascade was identified by measuring changes
      in cAMP levels after receptor activation, and its participation was confirmed by
      antibody-mediated inactivation. A2A -Ado-GPCR selective stimulation activates
      adenylyl cyclase 6 (AC6), which is bound to AKAP79/150, to synthesize cAMP which
      is used by two other AKAP79/150-tethered proteins: protein kinase A (PKA) and
      phosphodiesterase 3A (PDE3A). In contrast, A2B -Ado-GPCR stimulation activates D
      AKAP2-attached AC5 to generate cAMP, which is channeled to two other D-AKAP2
      tethered proteins: guanine-nucleotide exchange factor 2 (Epac2) and PDE3B. In
      both cases, prior activation of PKA or Epac2 with selective cAMP analogs prevents
      de novo cAMP synthesis. In addition, we show that cAMP does not diffuse between
      these protein macrocomplexes or 'signalosomes'. Evidence of coimmunoprecipitation
      and colocalization of some proteins belonging to each signalosome is presented.
      Each signalosome constitutes a minimal functional signaling unit with its own
      machinery to synthesize and regulate a sequestered cAMP pool. Thus, each
      signalosome is devoted to ensure the transmission of a unique and unequivocal
      message through the cell.

PMID- 27865068
TI  - Come one, come all...the sooner the better!

PMID- 27865069
TI  - Investing in our future: Update on the SCAI Emerging Leader Mentorship (ELM)
      Program.

PMID- 27865070
TI  - The newly occluded ectatic vessel: Not an ecstatic time.

PMID- 27865071
TI  - Routine invasive evaluation in non ST elevation myocardial infarction (NSTEMI
      ACS): Optimizing best.

PMID- 27865072
TI  - Long-term outcomes of the SMART stent in femoro-popliteal disease in TASC A/B
      lesions and TASC C/D lesions.

PMID- 27865073
TI  - STEMI with multivessel disease: An ongoing battle for the optimal treatment
      strategy.

PMID- 27865074
TI  - Hybrid transcatheter pulmonary valve replacement: Moving into the mainstream?

PMID- 27865075
TI  - Does the AToMIC trial explode concerns of contrast coagulopathy?

PMID- 27865076
TI  - Thrombus aspiration: Suck it up and keep looking for a niche.

PMID- 27865077
TI  - Renal sympathetic denervation: Recalculating....

PMID- 27865078
TI  - Carotid artery stenting: Avoiding the perfect storm.

PMID- 27865081
TI  - [Editorial. WHO Strategic Directions for Strengthening Nursing from now until
      2020.]

PMID- 27865080
TI  - Cell death-independent activities of the death receptors CD95, TRAILR1, and
      TRAILR2.
AB  - Since their identification more than 20 years ago, the death receptors CD95,
      TRAILR1, and TRAILR2 have been intensively studied with respect to their cell
      death-inducing activities. These receptors, however, can also trigger a variety
      of cell death-independent cellular responses reaching from the activation of
      proinflammatory gene transcription programs over the stimulation of proliferation
      and differentiation to induction of cell migration. The cell death-inducing
      signaling mechanisms of CD95 and the TRAIL death receptors are well understood.
      In contrast, despite the increasing recognition of the biological and
      pathophysiological relevance of the cell death-independent activities of CD95,
      TRAILR1, and TRAILR2, the corresponding signaling mechanisms are less understood
      and give no fully coherent picture. This review is focused on the cell death
      independent activities of CD95 and the TRAIL death receptors and addresses mainly
      three questions: (a) how are these receptors linked to noncell death pathways at
      the molecular level, (b) which factors determine the balance of cell death and
      cell death-independent activities of CD95 and the TRAIL death receptors at the
      cellular level, and (c) what are the consequences of the cell death-independent
      functions of these receptors for their role in cancer and inflammatory diseases.

PMID- 27865079
TI  - Blood flow evaluation using PINPOINT(r) in a case of incarcerated inguinal
      hernia: A case report.
AB  - Indocyanine green (ICG) fluorescence for intestinal blood flow has been reported,
      but application during laparoscopic surgery for incarcerated inguinal hernia has
      not been reported. Here, we report the case of a patient with an incarcerated
      inguinal hernia in whom the bowel was preserved after evaluation of intestinal
      blood flow with ICG fluorescence using PINPOINT(r), a brightfield full-color,
      near-infrared fluorescence camera. A man in his 80s was diagnosed with
      incarcerated inguinal hernia and underwent laparoscopic surgery. The ascending
      colon and mesentery showed deep red discoloration on gross evaluation. However,
      intravenous injection of ICG revealed uniform fluorescence of the mesentery and
      bowel wall, indicating the absence of irreversible ischemic changes of the bowel.
      As such, no resection was performed, and transabdominal preperitoneal patch
      plasty was completed. The patient had a good postoperative course. In this case,
      ICG fluorescence with the PINPOINT was useful to avoid bowel resection during
      laparoscopic surgery.

PMID- 27865082
TI  - [Nutritional self-care promotion in community-dwelling older people: a protocol
      of mixed method research].
AB  - AIM: To describe a research protocol designed to promote nutritional self-care in
      older people. The aims of the research are: a) to evaluate the effectiveness of a
      nutritional education intervention in changing knowledge, attitudes, and
      behaviors; b) to describe the nutritional self-care ability and activities; c) to
      identify the promoting factors and barriers that influence the changes in
      nutritional knowledge, behaviors and attitudes in home-dwelling older people.
      METHOD: Sequential explanatory mixed method design. The study will enroll 50
      people aged 65 years and over. In the first quantitative phase, a pre-test and
      post-test design will be used to deliver a nutritional intervention aimed to
      change knowledge, behaviors and attitudes toward nutrition. Using the
      quantitative study results, the qualitative study phase will be conducted by
      interviews in sub-groups of older people. In a third phase, the quantitative and
      qualitative study results will be integrated. Quantitative data will be analyzed
      using descriptive and inferential statistics and qualitative data will be
      analyzed through content analysis. RESULTS: The study will provide new knowledge
      on nutritional self-care in home-dwelling older adults and the factors promoting
      nutritional self-care. CONCLUSIONS: Nutritional self-care promotion is of pivotal
      importance for the nursing care provided to home-dwelling older people.
      Educational programs aimed at the maintenance of proper nutrition in the older
      adults may reduce malnutrition and the related diseases. Nutrition educational
      programs should be based on knowledge derived from research to tailor
      individualized nutritional interventions and to realize effective educational
      programs.

PMID- 27865083
TI  - [Shared decision making: a scoping review].
AB  - AIM: This research aimed to explore the literature regarding the model of the
      Shared Decision Making (SDM) in the field of nursing. METHOD: A scoping review
      was conducted. The electronic literature research was made on Medline, CINAHL,
      The Cochrane Library, Google Scholar, using a combination of key words: "Decision
      Making", "Shared Decision Making", "Nursing", "Nursing Patient relationship". The
      review was carried out following the Levac model. RESULTS: 29 studies were
      included, in a time range between 1972 and 2015. The analysis identifies the main
      characteristics of the SDM model, the tools for its implementation, the patients
      experience, the fields of application and the integration among SDM e evidence
      based practice. CONCLUSION: the analysis showed that the Shared Decision Making
      model is not widespread, especially in the Italian context. This phenomenon could
      be explained by three fundamental aspects. The concept is not widely disseminated
      and full scientific maturity. His application also seems to be related to
      extensive knowledge of gold standard interventions and possible alternatives.
      Finally, there are cultural barriers to the implementation of the SDM.

PMID- 27865084
TI  - [Cyberstalking among Italian nurses: a large multicentric study].
AB  - SCOPO: Determinare la prevalenza di cyberstalking tra gli infermieri italiani e
      valutare il livello di ansia e depressione nelle vittime. METODO: Da aprile a
      settembre 2014 e stato condotto uno studio multicentrico trasversale in un
      campione di infermieri italiani (n=997) utilizzando il questionario
      "Cyberstalking" per analizzare il fenomeno del cyberstalking. Ai partecipanti,
      che si sono autodefinite vittime di cyberstalking, e stato chiesto anche di
      compilare gli strumenti "Beck Depression Inventory" e "State-Trait Anxiety
      Inventory" per valutare, rispettivamente, i livelli di depressione ed ansia.
      RISULTATI: La prevalenza di cyberstalking tra gli infermieri italiani e risultata
      pari al 23.3%. Il 42.7% ha dovuto cambiare il proprio stile di vita e lavorativo.
      Il cyberstalker era prevalentemente di sesso maschile (52%) e, nel 49% dei casi,
      era un paziente. Le vittime hanno riferito moderati livelli di ansia (media=28.4,
      SD=23.2) e depressione (media=92.7, SD=18.3); i risultati hanno mostrato un
      aumento dei livelli di depressione negli infermieri esperti nell'utilizzo del
      computer, gestori di siti web o blog, e una correlazione negativa tra il livello
      di ansia e gli infermieri esperti (r = -0.264). CONCLUSIONI: Il cyberstalking e
      un fenomeno che si riscontra frequentemente tra gli infermieri. Il rapporto
      infermiere - paziente gioca un ruolo centrale nello sviluppo del fenomeno e le
      vittime hanno riferito disordini correlati allo stress che influenzano la vita
      lavorativa. Questi risultati preliminari potrebbero sensibilizzare, i dirigenti
      ospedalieri, la politica e i centri antiviolenza al fine di sviluppare strategie
      risolutiv.

PMID- 27865085
TI  - [L'impiego dell'ICNP(r) nella formazione infermieristica con modelli teorici
      infermieristici: una revisione della letteratura].
AB  - INTRODUCTION: The International Classification for Nursing Practice (ICNP(r)) is
      the only nursing terminology that has been accepted within the Family of
      International Classification of the World Health Organization. The academic
      teaching of ICNP(r) could contribute to improve nursing clinical practice.
      However, standards for its implementation in undergraduate nursing education
      together with a nursing theoretical model are not available. AIM: To know the
      state of the art about the use of ICNP(r) in undergraduate nursing education and
      its use with a nursing theoretical model. METHOD: A narrative literature review
      was conducted searching main health scientific databases and including
      monographs, statements from international associations, and published conference
      papers. RESULTS: Available literature about ICNP(r) implementation in nursing
      education and its use with theoretical models is limited. Results supported the
      organization of a specific course on ICNP(r) before clinical teaching programs,
      the development of paper or electronic ICNP(r) based educational tools, and the
      use of active learning strategies. Only three experiences reporting the use of
      ICNP(r) with theoretical models have been found. CONCLUSIONS: Both the use of
      ICNP(r) in nursing undergraduate education and its use according to one or more
      nursing theoretical models, could help students to learn nursing process.
      However, weak recommendations can be found in the literature to orient ICNP(r)
      implementation in undergraduate nursing education and/or with an explicit
      theoretical framework. Further studies focusing on these issues are strongly
      needed.

PMID- 27865086
TI  - [Knowledge and common sense of nurses on the health's inequities: an exploratory
      study.]
AB  - INTRODUCTION: The data for 2015 show of a general deterioration of living
      conditions and health of the population in Italy. The possible effects call the
      nurse to become involved in the subject of health inequalities. The study was
      designed with the goal of assessing how much the nurses know and perceive the
      correlation between the state of health of the population and system inequities.
      METHOD: An exploratory study was conducted through a bibliographic update
      compared to previous work and questionnaires in convenience samples of
      professionals and students of nursing and evaluation of results according to the
      mixed method perspective. RESULTS: The nursing literature on the quantity is very
      limited plan. The questionnaire provides useful answers to the evaluation of the
      perception of inequalities in health in terms of horizontal and vertical equity.
      CONCLUSION: Knowledge of health inequalities cannot be on the edge scientific
      work and the same professional literature. E 'need to reduce the gap between the
      aspects of values of their profession, which reverberate in the perception of
      existing inequities, and the full assumption of knowledge related to the socio
      economic determinants of health and disease.

PMID- 27865087
TI  - [Pain management in patients of a Swiss Institute of Oncology and the role of
      nurses: from programs to reality].
AB  - INTRODUCTION: In 2004, the Oncology Institute of Southern Switzerland (IOSI)
      started a program to improve cancer pain treatment, through training of health
      professionals and the introduction of monitoring tools . AIM: The aim is to
      evaluate patient relief from pain (effective pain control), with attention to
      nursing role (pain assessment, monitoring and documentation). METHOD:
      Retrospective study. The health records of patients admitted in the last three
      months of 2010 were consulted to evaluate how pain was assessed and managed.
      RESULTS: Out of 177 patients admitted, 93 (52.6 %) experienced pain during
      hospitalization and 85 were included in the analysis . Sixty-two out of 85 (72.9
      %) received drugs in reserve > = 2 days. They had pain from 2 to 28 days (median
      4). For 56/62 patients ( 90.3 %) analgesic therapy was changed one or more times
      and 40 of them ( 63.4 % ) received strong opioids during hospitalization . In
      8/62 cases pain wasn't documented, and overall, in 25/85 (29.4 %) intensity or
      any other feature weren't documented. CONCLUSIONS: At IOSI there is a good
      pharmacological control of pain. Analgesics are prescribed upon entry and are
      modulated according to patient needs, even with wide administration of opioids.
      The issue to improve is pain assessment and monitoring by nurses, whose role is
      mainly oriented to contribute to the pharmacological management of this symptom.

PMID- 27865088
TI  - Clinical competence in nursing: A concept analysis.
AB  - INTRODUCTION: In nursing, clinical competence is a central issue for patient care
      and a clear understanding of the concept is critical for nursing education and
      nursing discipline. AIM: To perform an analysis of the concept of 'clinical
      competence' in nursing to better understand its meaning. METHOD: The Walker and
      Avant's concept analysis model was used. A systematic literature review on
      international databases (PubMed, CINAHL, Scopus, Cochrane, Ovid, Open Grey) from
      1993 to 2015 was conducted. In the retrieved articles, the utilization of the
      concept of "clinical competence in nursing" was examined. RESULTS: According to
      Walker and Avant's method all the 8 steps were described on the basis of the
      findings of the literature review. Attributes, antecedents, consequences and
      empirical referents of the clinical competence in nursing have been identified
      and discussed and model, borderline, opposite cases were constructed. The
      relevance of the concept both for education and nursing professionalism have been
      also debated. CONCLUSION: This concept analysis has defined 'clinical competence
      in nursing' as 'a mix of skills, knowledge, attitudes and abilities that each
      nurse must possess to perform acceptably those duties directly related to patient
      care, in a specific clinical context and in given circumstances in order to
      promote, maintain and restore the health of patients'.

PMID- 27865089
TI  - The novel class of seven transmembrane segment inverted repeat carriers.
AB  - Solute carriers from the SLC4, SLC23, and SLC26 families are involved in pH
      regulation, vitamin C transport and ion homeostasis. While these families do not
      share any obvious sequence relationship, they are united by their unique and
      novel architecture. Each member of this structural class is organized into two
      structurally related halves of seven transmembrane segments each. These halves
      span the membrane with opposite orientations and form an intricately intertwined
      structure of two inverted repeats. This review highlights the general design
      principles of this fold and reveals the diversity between the different families.
      We discuss their domain architecture, structural framework and transport mode and
      detail an initial transport mechanism for this fold inferred from the recently
      solved structures of different members.

PMID- 27865091
TI  - Analysis of voluntary opening Ottobock Hook and Hosmer Hook for upper limb
      prosthetics: a preliminary study.
AB  - There are a number of prosthetic terminal devices which offer functional
      restoration to individuals with upper limb deficiencies. Hosmer and Ottobock are
      major commercial hook providers for prosthetic terminal devices. The concern of
      this paper is to analyse the voluntary opening (VO) Ottobock model 10A18 and
      Hosmer model 99P hooks (one band) during opening operation and to find out
      favourable features in the design. Two tests were conducted to analyse the
      performance of both hooks. The first test used a simple bench tool to investigate
      cable excursion and hook opening angle and the second test used force sensor to
      find out the force supplied at a different hook opening angle. The study found
      that the average cable excursion for both hooks is approximately 30% less than
      the hook's opening span with the force at the hook's tip section being inversely
      proportional to the force at the lateral section. Ottobock 10A18 has a better
      control for grasping larger objects, while Hosmer 99P has the highest average
      force at the tip section but yet less efficient in generating adequate force for
      activities of daily living. Favourable features identified are low cable
      excursion per hook opening span and balance lateral to hook tip pinch force.

PMID- 27865090
TI  - Characterization of the subcellular localization and nuclear import molecular
      mechanisms of herpes simplex virus 1 UL2.
AB  - As a crucial protein, the herpes simplex virus 1 (HSV-1) UL2 protein has been
      shown to take part in various stages of viral infection, nonetheless, its exact
      subcellular localization and transport molecular determinants are not well known
      thus far. In the present study, by using live cells fluorescent microscopy assay,
      UL2 tagged with enhanced yellow fluorescent protein was transiently expressed in
      live cells and showed a completely nuclear accumulation without the presence of
      other HSV-1 proteins. Moreover, the nuclear transport of UL2 was characterized to
      be assisted by multiple transport pathways through Ran-, importin alpha1-, alpha5
      , alpha7-, beta1- and transportin-1 cellular transport receptors. Consequently,
      these results will improve understanding of UL2-mediated biological functions in
      HSV-1 infection cycles.

PMID- 27865092
TI  - Control of bone and fat mass by oxytocin.
AB  - Osteoporosis and overweight/obesity constitute major worldwide public health
      burdens. Aging is associated with a decrease in hormonal secretion, lean mass and
      bone mass, and an increase in fat accumulation. It is established that both
      obesity and osteoporosis are affected by genetic and environmental factors, bone
      remodeling and adiposity are both regulated through the hypothalamus and
      sympathetic nervous system. Oxytocin (OT), belongs to the pituitary hormone
      family and regulates the function of peripheral target organs, its circulating
      levels decreased with age. Nowadays, it is well established that OT plays an
      important role in the control of bone and fat mass and their metabolism. Of note,
      OT and oxytocin receptor knock out mice develop bone defects and late-onset
      obesity. Thus OT emerges as a promising molecule in the treatment of osteoporosis
      and obesity as well as associated metabolic disorders such as type 2 diabetes and
      cardiovascular diseases. In this review, we will discuss findings regarding the
      OT effects on bone and fat mass.

PMID- 27865093
TI  - Maternal endothelial damage as a disorder shared by early preeclampsia, late
      preeclampsia and intrauterine growth restriction.
AB  - INTRODUCTION: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are
      separate disease entities that have frequently been reported as sharing the same
      pathogenesis. In both of them, angiogenesis disorders and generalized endothelial
      damage with an accompanying inflammation are the dominant symptoms. In this
      study, we attempted to prove that both these processes demonstrate the same
      profile in early PE, late PE and IUGR patients, while the only difference is in
      the degree of exacerbation of the lesions. PATIENTS, MATERIALS AND METHODS: In
      167 patients divided into four groups, three of those with early PE, late PE and
      IUGR and one control group, fms-like tyrosine kinase-1 (sFlt-1), placental growth
      factor (PlGF), high sensitive c-reactive protein (hsCRP) and fibronectin were
      determined. The behavior of these parameters in each of the groups was studied,
      and correlations between them were sought for. RESULTS: Higher concentrations of
      sFlt-1, hsCRP and fibronectin and a lower concentration of PlGF were found in the
      study groups compared to the control group. Significant correlations were
      observed between the factors concerned. CONCLUSIONS: The higher values of
      disordered angiogenesis markers, endothelial damage markers and inflammatory
      markers both in the PE and the intrauterine growth restriction (IUGR) groups
      suggest the existence of shared disorders in the development of these
      pathologies. The correlations between disordered angiogenesis markers and
      endothelial damage markers argue in favor of a mutual relationship between these
      two processes in the development of pathologies evolving as secondary to
      placental ischemia. The results obtained confirm that the lesion profiles are the
      same in both PE and IUGR patients, which can be utilized in developing common
      diagnostic criteria.

PMID- 27865094
TI  - Planned home birth and the association with neonatal hypoxic ischemic
      encephalopathy.
AB  - OBJECTIVE: To evaluate the association between planned home birth and neonatal
      hypoxic ischemic encephalopathy (HIE). METHODS: This is a case-control study in
      which a database of neonates who underwent head cooling for HIE at our
      institution from 2007 to 2011 was linked to New York City (NYC) vital records.
      Four normal controls per case were then randomly selected from the birth
      certificate data after matching for year of birth, geographic location, and
      gestational age. Demographic and obstetric information was obtained from the
      vital records for both the cases and controls. Location of birth was analyzed as
      hospital or out of hospital birth. Details from the out of hospital deliveries
      were reviewed to determine if the delivery was a planned home birth. Maternal and
      pregnancy characteristics were examined as covariates and potential confounders.
      Logistic regression was used to determine the odds of HIE by intended location of
      delivery. RESULTS: Sixty-nine neonates who underwent head cooling for HIE had
      available vital record data on their births. The 69 cases were matched to 276
      normal controls. After adjusting for pregnancy characteristics and mode of
      delivery, neonates with HIE had a 44.0-fold [95% confidence interval (CI) 1.7
      256.4] odds of having delivered out of hospital, whether unplanned or planned.
      Infants with HIE had a 21.0-fold (95% CI 1.7-256.4) increase in adjusted odds of
      having had a planned home birth compared to infants without HIE. CONCLUSION: Out
      of hospital birth, whether planned home birth or unplanned out of hospital birth,
      is associated with an increase in the odds of neonatal HIE.

PMID- 27865095
TI  - Assessment and Determinants of Spinal Pain in the Course of Disc Disorders
      Treated Surgically.
AB  - BACKGROUND Intervertebral disc disease is defined as a complex of structural
      changes in the aftermath of disorders of mutual elements, the structure of which
      form the discus intervertebralis and the spinal canal. The present work assessed
      pain in patients who were surgically treated due to spinal discopathy and
      analyzed factors that determine the condition. MATERIAL AND METHODS The research
      was carried on a group of 187 patients diagnosed with discopathy of the
      lumbosacral and cervical segment. The data are discussed in the context of
      medical records and the Visual Analogue Scale used for pain assessment. We used a
      prospective study plan with a 3-time assessment. RESULTS The pain level observed
      among patients prior to the procedure (M=6.52) was higher than after 7 days
      (M=3.15) and 6 months from the operation (M= 3.45). The highest level of pain
      (M=6.88), with a relatively high consistency among the patients (SD=2.25), was
      observed in the case of left-side hernia (H=7.31; p=0.023). The influence of the
      analyzed factors on pain experience markedly increased by the third assessment
      (R2=0.14), and was strongly associated with the type of work performed by the
      patient. CONCLUSIONS Surgical operation significantly reduces pain in patients
      with disc disorders. The level of pain is predominantly affected by the location
      of the hernia and the type of work performed by the patient.

PMID- 27865096
TI  - Salmonellosis in Poland in 2014
AB  - OBJECTIVE: The aim of the study is to assess the epidemiological situation of
      salmonellosis in Poland in 2014 in comparison to the previous years. MATERIAL AND
      METHODS: The evaluation was based on the data from the bulletin "Infectious
      diseases and poisoning in Poland 2014", information from the laboratories of
      sanitary-epidemiological stations and reports from the epidemiological
      investigations in outbreaks of salmonellosis, sent by the sanitary
      epidemiological stations to the Department of Epidemiology, as well as the data
      from the Department of Demographic Studies of the Central Statistical Office.
      Cases were classified according to the definitions adopted in the UE. RESULTS: In
      2014, a total number of 8 392 cases of salmonellosis derived from animals were
      reported, including 8 197 cases of intestinal salmonellosis and 195 cases of
      extraintestinal. The total incidence was 21.8/100 000. Almost 96% of the cases
      met the criteria for a confirmed case. The number of registered cases was, for
      the first time since many years, higher than in the previous year, but still
      lower than the median for 2008-2012. A very high percentage (approximately 70%)
      of hospitalizations remains among patients diagnosed with salmonellosis.
      Approximately 33% of all cases in outbreaks of salmonellosis were hospitalized.
      The highest incidence was among children under the age of 5 years. Salmonellosis
      was reported as the cause of death for 13 patients. In 2014 there were 171
      outbreaks reported with Salmonella as an etiological agent. Majority of them were
      small outbreaks limited to the family in singular household, and the total number
      of cases in those outbreaks amounted to 1 229 people. In Poland the most common
      etiological agent of salmonellosis is (and have been for many years) S.
      Enteritidis. CONCLUSIONS: In 2014, the first time in many years, an increase was
      recorded in the annual number of cases of salmonellosis. A very high percentage
      of hospitalizations for salmonellosis cases indicates a relatively rare practice
      among GPs in ordering laboratory testing in patients presenting with
      gastroenteritis. This causes significant underreporting of salmonellosis in
      throughout the country and indicates the need to introduce mechanisms which would
      make laboratory testing for salmonellosis as a recommended practice.

PMID- 27865097
TI  - Etiology and treatment of acute inferior vena cava thrombosis.
AB  - Inferior vena cava thrombosis (IVCT) is a rare but severe disease that is
      associated with a high rate of mortality. IVCT can be categorized into primary
      versus secondary thrombosis dependent upon the underlying pathophysiology. The
      diagnosis includes both clinical probability assessment as well as the imaging
      evaluation. The optimal therapeutic strategy remains the target of continued
      research. Although anticoagulation therapy remains fundamental in treating IVCT,
      its inherent limitations have led to the use of minimally invasive, endovascular
      treatment options, including transcatheter thrombolysis, mechanical thrombectomy
      or a combination of these techniques. This review focuses on the etiology,
      diagnostic assessment, and endovascular treatment options for IVCT.

PMID- 27865098
TI  - Dying two deaths - programmed cell death regulation in development and disease.
AB  - Programmed cell death (PCD) is a fundamental cellular process that has adopted a
      plethora of vital functions in multicellular organisms. In plants, PCD processes
      are elicited as an inherent part of regular development in specific cell types or
      tissues, but can also be triggered by biotic and abiotic stresses. Although over
      the last years we have seen progress in our understanding of the molecular
      regulation of different plant PCD processes, it is still unclear whether a common
      core machinery exists that controls cell death in development and disease. In
      this review, we discuss recent advances in the field, comparing some aspects of
      the molecular regulation controlling developmental and pathogen-triggered PCD in
      plants.

PMID- 27865099
TI  - Assessing symptoms during comprehensive interventions for young children with
      autism spectrum disorder: Development and preliminary analysis of the Autism
      Behaviour Coding System (ABCS).
AB  - The aims of this paper are to present the Autism Behaviour Coding System (ABCS),
      a novel, video-based observational instrument for assessing core autism symptoms
      during intensive early interventions in autism spectrum disorder (ASD), to
      provide preliminary data on its psychometric characteristics and to discuss its
      clinical utility. Video recordings of child-therapist interactions during the
      'Fruhintervention bei autistischen Storungen' (FIAS) were coded by treatment
      independent raters who were blind with respect to the temporal order of the
      sequences. We assessed inter-rater reliability using intra-class correlations
      (ICCs). Mean ICCs ranged from 0.85 to 0.90. We analysed the sensitivity of the
      ABCS to change by comparing the change in ABCS scores with the change in a
      validated external measure of level of functioning (Developmental Disorder-Child
      Global Assessment of functioning Scale, DD-C-GAS) in a sample of 15 children who
      received intensive treatment. Both the ABCS and DD-C-GAS indicated that the
      intervention improved symptoms. The ABCS has promise as a research instrument and
      has good to excellent inter-rater agreement and sensitivity to intervention
      related changes. This pilot study suggests that the ABCS may be useful as an
      objective method of assessing the proximal effects of therapy in young children
      with ASD.

PMID- 27865100
TI  - Walking away from depression-motor activity increases ratings of mood and
      incentive drive in patients with major depression.
AB  - Reduced motor activity is associated with depression. Lewinsohn's cognitive
      behavioural model of depression assumes a lack of positive experience due to a
      reduced level of activity as a key aspect of depression. The acute relationship
      between motor activity and mood as well as between motor activity and incentive
      drive (the motivation to engage in activities) is unknown. An augmentation of
      mood and incentive drive could precede or follow motor activity. We examined (1)
      whether motor activity would be correlated with the course of depression and (2)
      the temporal relationship between motor activity and acute changes in mood and
      incentive drive. Motor activity was measured with actigraphy in 12 patients with
      depression for one week. Severity of depression was assessed before and at the
      end of the study with depression rating scales. The patients reported mood and
      incentive drive once per hour. With lag sequential analysis, the temporal
      relationship between motor activity and mood and incentive drive was evaluated.
      Higher motor activity was associated with depression improvement. Motor activity
      had an acute association with mood and incentive drive, especially one hour after
      activity. The results support the Lewinsohn's model of depression and underline
      the impact of behavioural activation in antidepressant treatment.

PMID- 27865101
TI  - Diagnostic guide enabling distinction between taphonomic stains and enamel
      hypomineralisation in an archaeological context.
AB  - OBJECTIVE: Molar Incisor Hypomineralisation (MIH) is a structural anomaly that
      affects the quality of tooth enamel and has important consequences for oral
      health. The developmentally hypomineralised enamel has normal thickness and can
      range in colour from white to yellow or brown with or without surface breakdown.
      The possibility of finding MIH in 'ancient populations' could downplay several
      current aetiological hypotheses (e.g., dioxin derivatives, bisphenols,
      antibiotics) without excluding the possible multifactorial aspect of the anomaly.
      In an archaeological context, chemical elements contained in the burial ground
      can stain teeth yellow or brown and therefore might create a taphonomic bias. The
      purpose of the present study is to test a proposed diagnostic guide enabling
      determination of the pathological or taphonomic cause of enamel discolouration
      and defects that resemble MIH present on 'ancient teeth'. DESIGN: Two sample
      groups including MIH discoloration (n=12 teeth) from living patients, taphonomic
      discoloration (n=9 teeth) and unknown discoloration (n=2 teeth) from medieval
      specimens were tested. Three non-destructive methods-Raman spectroscopy, X-ray
      micro-computed tomography and X-ray fluorescence were utilised. RESULTS:
      Hypomineralised enamel has decreased mineral density (p<0.0001) and increased
      phosphate/beta-carbonate ratio (p<0.01) compared to normal enamel whereas
      relative concentrations of manganese, copper, iron and lead are similar. In
      taphonomic discoloration, relative concentrations of these elements are
      significantly different (p<0.05) to normal enamel whereas mineral density and
      Raman spectra profile are comparable. CONCLUSIONS: Enamel hypomineralisation can
      be distinguished from taphonomic staining in archaeological teeth.

PMID- 27865102
TI  - Pharmacotherapy for residual excessive sleepiness and cognition in CPAP-treated
      patients with obstructive sleep apnea syndrome: A systematic review and meta
      analysis.
AB  - Pharmacotherapy has been used as an adjunct to CPAP for treatment of residual
      excessive sleepiness in patients with a diagnosis of obstructive sleep apnea
      syndrome (OSAS). However, no studies with a high level of evidence have been
      conducted to support this practice and confirm its effectiveness. We conducted a
      meta-analysis to summarize and quantify the effects of pharmacological treatment
      in adults with OSAS who experience residual excessive sleepiness despite adequate
      CPAP use. We reviewed clinical trials that compared medications to placebo and
      evaluated the outcomes residual excessive sleepiness, cognition, and quality of
      life, as well as treatment effectiveness and safety. The MEDLINE, EMBASE, LILACS,
      Cochrane Central Register of Controlled Trials - CENTRAL, and PsycINFO electronic
      databases were searched using highly sensitive search strategies. Trials were
      only included if measures were taken to ensure effective CPAP treatment. Eight
      randomized clinical trials were included. Pharmacotherapy with modafinil and
      armodafinil led to improvement of excessive daytime sleepiness,
      attention/alertness, and clinical condition as measured with the CGI-C. No
      improvements in quality of life or other cognitive domains (including memory,
      executive function, and language) could be confirmed. Pharmacotherapy did not
      cause any severe adverse effects, but was associated with significant dropout
      rates as compared with placebo. In conclusion, although our results demonstrate
      the effectiveness of pharmacological treatment as an adjunct to CPAP, further
      investigation is necessary to improve confidence in its effects. Many findings on
      the impact of pharmacotherapy on cognition and quality of life were evaluated
      through analysis of single studies, with heterogeneity in tests and absence of
      standardization, which reduced certainty as to whether actual improvement
      occurred in these outcomes.

PMID- 27865103
TI  - Rethinking pathology in adolescent self-harm: Towards a more complex
      understanding of risk factors.
AB  - Researchers have begun to consider whether there may be more than one
      psychological profile to describe adolescents who engage in self-harm. Limited
      past research suggests multiple different profiles. Australian high school
      students (n = 1,521, age 11-19, 56.4% female) completed an online questionnaire
      reporting risk and protective factors and self-harm frequency. Non-hierarchical
      cluster analysis allocated 256 students who reported 6-month self-harm to
      mutually exclusive profiles based on psychological similarity. Five distinct
      psychological profiles were identified: 1) Psychologically 'normal'; 2) Anxiety
      symptoms; 3) Impulsive; 4) Pathological; and 5) Pathological-Impulsive. The
      proportion of adolescents that reported 11 or more episodes of self-harm varied
      from 5.7% in the psychologically 'Normal' group to 27.7% in the 'Pathological-
      Impulsive' group. These results indicate that multiple psychological profiles
      exist. Adolescents with different risk factors may require disparate strategies
      for treatment and prevention. Given the variability in profiles, screening may
      assist in detecting adolescents who self-harm.

PMID- 27865104
TI  - Detection of low-abundance biomarker lipocalin 1 for diabetic retinopathy using
      optoelectrokinetic bead-based immunosensing.
AB  - Early diagnosis of diabetic retinopathy (DR) is vital but challenging. DR is a
      common complication and a major cause of vision loss in patients with diabetes
      mellitus. Without appropriate medical intervention, visual impairment may become
      a great burden to our healthcare system. In clinical practice, the current
      diagnostic methods, such as fluorescence angiography and optical coherence
      tomography, remain constrained by non-quantitative examinations and individual
      ophthalmologists' experiences. Late diagnosis often prevents early treatment. To
      address the constraints on current diagnostics, this study developed an
      optoelectrokinetic bead-based immunosensing technique for detecting lipocalin 1
      (LCN1), a DR biomarker. The concentration level of LCN1 in the tears of DR
      patients increases with DR severity. The immunoassay was dependent on the
      formation of sandwiched immunocomplexes on the particles. A secondary antibody
      labeled with dyes/quantum dots (QDs) was used to visualize the presence of the
      target antigens. Rapid electrokinetic patterning (REP), an optoelectrokinetic
      technique, was used to dynamically enhance the fluorescent signal by
      concentrating the modified particles. The limit of detection (LOD) of the
      technique could reach 110pg/mL. Only 1.5MUL of a sample fluid was required for
      the measurement. Our results showed that highly sensitive and improved LOD is
      subjected to particle stacking, small particle size, and compact cluster. By
      labeling different particle sizes with dyes/QDs for LCN1 and TNF-alpha, we
      successfully used REP to detect the two DR biomarkers on the same platform. The
      development of an optoelectrokinetic bead-based immunosensing technique can
      provide new insights into diagnosing other low-abundance diseases in the future.

PMID- 27865105
TI  - Sensitive and rapid detection of microRNAs using hairpin probes-mediated
      exponential isothermal amplification.
AB  - MicroRNAs (miRNAs) play significant roles in a diverse range of biological
      progress and have been regarded as biomarkers and therapeutic targets in cancer
      treatment. Here, we develop a rapid and sensitive miRNA assay on the basis of
      exponential isothermal amplification in combination with the hairpin probes,
      which was designed for sensitive detection of miRNA. The binding of target miRNA
      with a linear DNA template initiates exponential isothermal amplification
      reaction (EXPAR) and generates the universal triggers which are complementary to
      the 3' protruding end of hairpin probe1(HP1). These triggers function not only as
      the primers to unfold the hairpin probes through catalysed hairpin assembly(CHA),
      generating distinct fluorescence signals, but also as the primer to initiate the
      next EXPAR. Moreover, CHA can release new triggers to initiate EXPAR or CHA. Thus
      this hairpin probes-mediated exponential isothermal amplification assay exhibits
      high sensitivity with a detection limit of 3.0*10-15M. More importantly, the
      isothermal condition and simple fluorescence measurement would greatly promote
      the development of a fast, point-of-care detection system. It can be completed in
      an hour which can effectively avoid miRNA from degradation. This hairpin probe
      based circular exponential amplification assay holds a great promise for further
      application in biomedical research and early clinical diagnosis.

PMID- 27865106
TI  - High-speed biosensing strategy for non-invasive profiling of multiple cancer
      fusion genes in urine.
AB  - Aberrant chromosal rearrangements, such as the multiple variants of TMPRSS2:ERG
      fusion gene mutations in prostate cancer (PCa), are promising diagnostic and
      prognostic biomarkers due to their specific expression in cancerous tissue only.
      Additionally, TMPRSS2:ERG variants are detectable in urine to provide non
      invasive PCa diagnostic sampling as an attractive surrogate for needle biopsies.
      Therefore, rapid and simplistic assays for identifying multiple urinary
      TMPRSS2:ERG variants are potentially useful to aid in early cancer detection,
      immediate patient risk stratification, and prompt personalized treatment.
      However, current strategies for simultaneous detection of multiple gene fusions
      are limited by tedious and prolonged experimental protocols, thus limiting their
      use as rapid clinical screening tools. Herein, we report a simple and rapid gene
      fusion strategy which expliots the specificity of DNA ligase and the speed of
      isothermal amplification to simultaneously detect multiple fusion gene RNAs
      within a short sample-to-answer timeframe of 60min. The method has a low
      detection limit of 2 amol (1000 copies), and was successfully applied for non
      invasive fusion gene profiling in patient urine samples with subsequent
      validation by a PCR-based gold standard approach.

PMID- 27865108
TI  - Self-powered sensing platform equipped with Prussian blue electrochromic display
      driven by photoelectrochemical cell.
AB  - By incorporating the Prussian Blue (PB) electrochromic display as cathode, a
      solar-driven photoelectrochemical (PEC) cell was constructed through combining
      sandwich-structured graphite-like carbon nitride (g-C3N4)-Au-branched-titanium
      dioxide (B-TiO2) nanorods as photoanode for self-powered hydrogen peroxide (H2O2)
      sensing, which exhibits both direct photoelectrochemical and electrochromic
      response. The gold nanoparticles (Au NPs) sandwiched between the B-TiO2 nanorods
      and the g-C3N4 layer served as electron relay as well as plasmonic
      photosensitizer to enhance the solar-to-chemical energy conversion efficiency.
      Owing to the effective disproportionation of H2O2 and specific recognition of
      mannose on cell surface, concanavalin-A conjugated porous AuPd alloy
      nanoparticles were introduced as the catalytically active nanolabels promoting
      generation of hydroxyl radicals (.OH). Based on the cleavage of DNA with the
      participation of .OH radicals generated by the decomposition of H2O2 under the
      catalysis of AuPd alloy result in the disassembly of cancer cells to achieve
      further signal enhancement. The multiple-signal-output sensing response not only
      provides a promising strategy for different analytical purposes based on novel
      stimuli-responsive materials, but also enhances the reliability in the analyte
      detection.

PMID- 27865109
TI  - Carbon-based nanocomposites with aptamer-templated silver nanoclusters for the
      highly sensitive and selective detection of platelet-derived growth factor.
AB  - We synthesized two kinds of carbon-based nanocomposites of silver nanoclusters
      (AgNCs). An aptamer for targeted platelet-derived growth factor-BB (PDGF-BB)
      detection was used as the organic phase to produce AgNCs@Apt, three dimensional
      reduced graphene oxide@AgNCs@Aptamer (3D-rGO@AgNCs@Apt), and graphene quantum
      dots@AgNCs@Aptamer (GQD@AgNCs@Apt) nanocomposites. The formation mechanism of the
      developed nanocomposites was described by detailed characterizations of their
      chemical and crystal structures. Subsequently, the as-synthesized nanoclusters
      containing aptamer strands were applied as the sensitive layers to fabricate a
      novel electrochemical aptasensor for the detection of PDGF-BB, which may be
      directly used to determine the target protein. Electrochemical impedance spectra
      showed that the developed 3D-rGO@AgNCs@Apt-based biosensor exhibited the highest
      sensitivity for PDGF-BB detection among three kinds of fabricated aptasensors,
      with an extremely low detection limit of 0.82pgmL-1. In addition, the 3D
      rGO@AgNCs@Apt-based biosensor showed high selectivity, stability, and
      applicability for the detection of PDGF-BB. This finding indicated that the AgNC
      based nanocomposites prepared by a one-step method could be used as an
      electrochemical biosensor for various detection procedures in the biomedical
      field.

PMID- 27865107
TI  - A luminescent lanthanide coordination polymer based on energy transfer from metal
      to metal for hydrogen peroxide detection.
AB  - A bimetal lanthanide coordination polymer nanoparticle (ATP-Ce/Tb-Tris CPNs) with
      good biocompatibility was synthesized in Tris-HCl buffer using adenosine
      triphosphate (ATP) molecules as the bridge ligands. The large absorption cross
      section and suitable emission energy of Ce3+ matching to the adsorption energy of
      Tb3+(4fn) results in the efficient energy transfer from Ce3+ to Tb3+, thus the
      synthesized ATP-Ce/Tb-Tris CPNs exhibit the characteristic green emission of
      Tb3+. Such energy transfer from metal to metal in fluorescent lanthanide
      coordination polymer nanoparticles (Ln-CPNs) has been demonstrated. It is found
      that the oxidation of Ce3+ in ATP-Ce/Tb-Tris CNPs to Ce4+ would interrupt the
      energy transfer from Ce3+ to Tb3+, leading to fluorescence quenching of Tb3+. On
      the basis of this quenching mechanism, ATP-Ce/Tb-Tris CPNs has been successfully
      used to detect reactive oxygen H2O2 with detection limit as low as 2nM. If
      glucose oxidase is present in the system, glucose can be determined using the ATP
      Ce/Tb-Tris CNPs nanosensor.

PMID- 27865110
TI  - Specifically and wash-free labeling of SNAP-tag fused proteins with a hybrid
      sensor to monitor local micro-viscosity.
AB  - Viscosity, as one of the major factors of intracellular microenvironment,
      influences the function of proteins. To detect local micro-viscosity of a
      protein, it is a precondition to apply a viscosity sensor for specifically target
      to proteins. However, all the reported small-molecule probes are just suitable
      for sensing/imaging of macro-viscosity in biological fluids of entire cells or
      organelles. To this end, we developed a hybrid sensor BDP-V BG by connecting a
      viscosity-sensitive boron-dipyrromethene (BODIPY) molecular rotor (BDP-V) to O6
      benzylguanine (BG) for specific detection of local micro-viscosity of SNAP-tag
      fused proteins. We measured and calculated the reaction efficiency between the
      sensor and SNAP-tag protein in vitro to confirm the high labeling specificity. We
      also found that the labeling reaction results in a 53-fold fluorescence
      enhancement for the rotor, which qualifies it as a wash-free sensor with
      ignorable background fluorescence. The high sensitivity of protein labeled sensor
      (BDP-V-SNAP) to the changes of local viscosity was evaluated by detecting the
      enhancement of fluorescence lifetimes. Further, with the sensor BDP-V BG, we
      achieved high specific labeling of cells expressing two SNAP-tag fused proteins
      (nuclear histone H2B and mitochondrial COX8A). Two-photon excited fluorescence
      lifetime imaging revealed that, the micro-viscosities nearby the SNAP-tag fused
      two proteins are distinct. The different changes of local micro-viscosity of SNAP
      tag fused histone protein in apoptosis induced by three nucleus-targeted drugs
      were also characterized for the first time.

PMID- 27865111
TI  - Camelid and shark single domain antibodies: structural features and therapeutic
      potential.
AB  - In addition to canonical antibodies composed of heavy and light chains, the
      adaptive immune systems of camelids and cartilaginous fish comprise heavy-chain
      only isotypes (HcAb) devoid of light chains, where antigen-binding is mediated
      exclusively by one variable domain. Due to their inherent favorable attributes,
      such as high affinity and specificity for their cognate antigen, extraordinary
      stability, small size and, most importantly, the possibility to complement
      classical antibodies in terms of 'drugable' target-space, HcAb-derived entities
      evolved as promising candidates for biomedical applications of which many have
      already proven to be successful in early stage clinical trials.

PMID- 27865113
TI  - Implicit moral evaluations: A multinomial modeling approach.
AB  - Implicit moral evaluations-i.e., immediate, unintentional assessments of the
      wrongness of actions or persons-play a central role in supporting moral behavior
      in everyday life. Yet little research has employed methods that rigorously
      measure individual differences in implicit moral evaluations. In five
      experiments, we develop a new sequential priming measure-the Moral Categorization
      Task-and a multinomial model that decomposes judgment on this task into multiple
      component processes. These include implicit moral evaluations of moral
      transgression primes (Unintentional Judgment), accurate moral judgments about
      target actions (Intentional Judgment), and a directional tendency to judge
      actions as morally wrong (Response Bias). Speeded response deadlines reduced
      Intentional Judgment but not Unintentional Judgment (Experiment 1). Unintentional
      Judgment was stronger toward moral transgression primes than non-moral negative
      primes (Experiments 2-4). Intentional Judgment was associated with increased
      error-related negativity, a neurophysiological indicator of behavioral control
      (Experiment 4). Finally, people who voted for an anti-gay marriage amendment had
      stronger Unintentional Judgment toward gay marriage primes (Experiment 5). Across
      Experiments 1-4, implicit moral evaluations converged with moral personality:
      Unintentional Judgment about wrong primes, but not negative primes, was
      negatively associated with psychopathic tendencies and positively associated with
      moral identity and guilt proneness. Theoretical and practical applications of
      formal modeling for moral psychology are discussed.

PMID- 27865112
TI  - Recent advances in understanding proton coupled peptide transport via the POT
      family.
AB  - The POT family of membrane transporters use the inwardly directed proton
      electrochemical gradient to drive the uptake of essential nutrients into the
      cell. Originally discovered in bacteria, members of the family have been found in
      all kingdoms of life except the archaea. A remarkable feature of the family is
      their diverse substrate promiscuity. Whereas in mammals and bacteria they are
      predominantly di- and tri-peptide transporters, in plants the family has diverged
      to recognize nitrate, plant defence compounds and hormones. This promiscuity has
      led to the development of peptide-based pro-drugs that use PepT1 and PepT2, the
      mammalian homologues, to improve oral drug delivery. Recent crystal structures
      from bacterial and plant members of the family have revealed conserved features
      of the ligand-binding site and provided insights into post-translational
      regulation. Here I review the current understanding of transport, ligand
      promiscuity and regulation within the POT family.

PMID- 27865114
TI  - The effect of selenium and UV radiation on leaf traits and biomass production in
      Triticum aestivum L.
AB  - UV radiation as an evolutionarily important environmental factor, significantly
      affects plants traits and alters the effects of other environmental factors.
      Single and combined effects of ambient UV radiation, its exclusion, and Se foliar
      treatments on Si concentrations and production of Si phytoliths in wheat
      (Triticum aestivum L.) cv. 'Reska' were studied. The effects of these treatments
      on growth parameters of the plants, structural and biochemical traits of the
      leaves, and interactions of the leaves with light, as Si incrustation is the
      first barrier to light at the leaf surface were also examined. Under ambient UV
      radiation and foliar treatment with 10mgL-1 sodium selenate solution, there was a
      trade-off between the plant investment in primary and secondary metabolism, as
      the production of UV-absorbing compounds was enhanced while photosynthetic
      pigment levels were reduced. Independent of Se treatment, ambient UV radiation
      lowered respiratory potential, Ca concentration, and leaf thickness, and
      increased Si concentration, Si phytoliths formation, and cuticle thickness. The
      Se treatment has little effect on plant traits and biomass production but it
      increased Se concentrations in the plants by >100-fold, independent of UV
      radiation. In combination with UV radiation Se strengthen the protection of
      plants against stress by increasing the amount of UV absorbing compounds, light
      reflectance and transmittance.

PMID- 27865115
TI  - Phytochelatin synthesis in Dunaliella salina induced by arsenite and arsenate
      under various phosphate regimes.
AB  - This study investigated the dynamic variations in thiol compounds, including
      cysteine (Cys), glutathione (GSH), and phytochelatins (PCs), in Dunaliella salina
      samples exposed to arsenite [As(III)] and arsenate [As(V)] under various
      phosphate (PO43-) regimes. Our results showed that GSH was the major non-protein
      sulfhydryl compound in D. salina cells. As(III) and As(V) induced PC syntheses in
      D. salina. PC2, PC3, and PC4 were all found in algal cells; the PC concentrations
      decreased gradually while exposed to As for 3 d. The synthesis of PC2-3 was
      significantly affected by As(III) and As(V) concentrations in the cultures. More
      PCs were detected in the As(V)-treated algal cells compared with the As(III)
      treatment. PC levels increased with As(III)/As(V) amount in the medium, but
      remained stable after 112MUgL-1 As(V) exposure. In contrast, significant
      (p<0.001) positive correlations were observed between PC synthesis and
      intracellular As(III) content or As accumulation in As(III)-treated algal cells
      during the 72-h exposure. PO43- had a significant influence on the PC synthesis
      in algal cells, irrespective of the As-treated species. Reductions in As uptake
      and subsequent PC synthesis by D. salina were observed as the PO43- concentration
      in the growth medium increased. L-Buthionine sulfoximine (BSO) differentially
      influenced PC synthesis in As-treated D. salina under different extracellular
      PO43- regimes. Overall, our data demonstrated that the production of GSH and PCs
      was affected by PO43- and that these thiols played an important role in As
      detoxification by D. salina.

PMID- 27865116
TI  - Comparison of contemporaneous responses for EQ-5D-3L and Minnesota Living with
      Heart Failure; a case for disease specific multiattribute utility instrument in
      cardiovascular conditions.
AB  - BACKGROUND: The EQ-5D-3L, a generic multi-attribute utility instrument (MAUI), is
      widely employed to assist in economic evaluations in health care. The EQ-5D-3L
      lacks sensitivity when used in conditions such as cardiovascular disease (CVD).
      Although there are number of CVD specific quality of life instruments, currently,
      there are no CVD specific MAUIs. The aim of this study is to investigate the
      discriminative ability and responsiveness of the EQ-5D-3L and the Minnesota
      Living with Heart Failure Questionnaire (MLHF), a CVD specific quality of life
      instrument in a group of heart failure patients. METHODS: The psychometric
      performance of the EQ-5D-3L and the MLHF was assessed using data from a
      randomised trial for a heart failure management intervention. The two instruments
      were compared for discrimination, responsiveness and agreement. The severity
      groups were defined using New York Heart Association functional classes. RESULTS:
      The effect sizes for severe classes were generally similar showing good
      discrimination. The MLHF recorded better responsiveness between the time points
      than the EQ-5D-3L which was indicated by higher effect sizes and standardised
      response means. The change in MLHF summary scores between the time points was
      significant (p<0.005; paired t-test). The overall agreement between the two
      measures was low. CONCLUSION: The low correlation indicates that the two
      classification systems cover different aspects of health space. Comparison of CVD
      specific instruments with other generic MAUIs such as EQ-5D-3L and AQOL-8D is
      recommended for further research.

PMID- 27865117
TI  - Catalytic iron in acute myocardial infarction complicated by cardiogenic shock -
      A biomarker substudy of the IABP-SHOCK II-trial.
AB  - BACKGROUND: Catalytic iron (CI) is unbound ferric iron with the potential to
      generate reactive oxygen species with further deleterious vascular effects. In
      acute coronary syndromes, high levels of CI are linked to all-cause mortality.
      The prognostic impact of CI and iron metabolism in cardiogenic shock (CS) is
      currently undetermined. Aims of this study were to investigate the prognostic
      impact of CI and to identify predictors of high CI levels in patients with CS
      complicating acute myocardial infarction. METHODS: The Intraaortic Balloon Pump
      in Cardiogenic Shock II (IABP-SHOCK II) trial randomized 600 patients with CS to
      either therapy with intraaortic balloon pump or control. In 185 of these
      patients, blood samples were systematically collected at baseline and day 3. CI
      levels were measured using a modified bleomycin detectable iron assay.
      Furthermore, levels of free hemoglobin, total serum iron, transferrin, total iron
      binding capacity, ferritin, hepcidin, and transferrin saturation were assessed.
      RESULTS: Patients with baseline CI levels in the highest quartile had a worse
      outcome in comparison to patients with lower CI (day 1: HR 1.91 [1.11-3.31],
      p=0.005; day 3: HR 2.15 [1.06-4.34], p=0.01). In multivariable Cox-regression
      analysis baseline CI remained an independent predictor of 30-day mortality (HR
      per 10LOG 2.08 [1.25-3.47], p=0.005). Predictors of CI levels on day 3 were
      baseline CI, bleeding events, and baseline troponin T. CONCLUSIONS: CI levels
      were associated with increased short-term mortality in CS complicating acute
      myocardial infarction. High levels of CI at day 3 were associated with bleeding
      and high troponin levels.

PMID- 27865119
TI  - Does haptic steering guidance instigate speeding? A driving simulator study into
      causes and remedies.
AB  - An important issue in road traffic safety is that drivers show adverse behavioral
      adaptation (BA) to driver assistance systems. Haptic steering guidance is an
      upcoming assistance system which facilitates lane-keeping performance while
      keeping drivers in the loop, and which may be particularly prone to BA. Thus far,
      experiments on haptic steering guidance have measured driver performance while
      the vehicle speed was kept constant. The aim of the present driving simulator
      study was to examine whether haptic steering guidance causes BA in the form of
      speeding, and to evaluate two types of haptic steering guidance designed not to
      suffer from BA. Twenty-four participants drove a 1.8m wide car for 13.9km on a
      curved road, with cones demarcating a single 2.2m narrow lane. Participants
      completed four conditions in a counterbalanced design: no guidance (Manual),
      continuous haptic guidance (Cont), continuous guidance that linearly reduced
      feedback gains from full guidance at 125km/h towards manual control at 130km/h
      and above (ContRF), and haptic guidance provided only when the predicted lateral
      position was outside a lateral bandwidth (Band). Participants were familiarized
      with each condition prior to the experimental runs and were instructed to drive
      as they normally would while minimizing the number of cone hits. Compared to
      Manual, the Cont condition yielded a significantly higher driving speed (on
      average by 7km/h), whereas ContRF and Band did not. All three guidance conditions
      yielded better lane-keeping performance than Manual, whereas Cont and ContRF
      yielded lower self-reported workload than Manual. In conclusion, continuous
      steering guidance entices drivers to increase their speed, thereby diminishing
      its potential safety benefits. It is possible to prevent BA while retaining
      safety benefits by making a design adjustment either in lateral (Band) or in
      longitudinal (ContRF) direction.

PMID- 27865120
TI  - Polybrominated diphenyl ethers (PBDEs) in Great Lakes fish: Levels, patterns,
      trends and implications for human exposure.
AB  - Levels of polybrominated diphenyl ethers (PBDEs) were measured in edible portions
      of Great Lakes fish, with the goal of examining patterns/trends and evaluating
      implications for human exposure. A total of 470 fillets of 18 fish species
      collected from various parts of the Canadian waters of the Great Lakes between
      2006 and 2013 were analyzed for 17 (expanded to 33 in 2009) PBDEs. For a limited
      number of species, fillet to whole body and fillet to eggs PBDEs were compared to
      examine pattern and concentration among tissue types. Levels and patterns of
      PBDEs varied dramatically within and among the 18 fish species. Bottom dwelling
      Common Carp (and White Sucker) exhibited the highest ?PBDE levels (27-71ng/g).
      Lake Trout and Lake Whitefish from Lake Superior had higher levels than those
      from the other Great Lakes; otherwise the spatial trend was Lake
      Ontario?Erie~Huron~Superior. The measured levels would result in restriction on
      consumption of only Common Carp from the Toronto waterfront area, which is in
      proximity to the most urbanised region on the Canadian side of the basin. Deca
      BDE was the major congener in panfish, while BDE-47 was the major congener in top
      predators and its contribution to ?PBDE increased with the contamination.
      Although ?PBDE was related to fish length and lipid content when all measurements
      were pooled, the relationships were variable for individual sampling events
      (species/location/year). Whole body ?PBDE for bottom dweller Brown Bullhead and
      Common Carp were 2.6-4.9 times greater and egg ?PBDE for four fatty Salmon/Trout
      species were same to 6.5 times greater than the corresponding fillet
      concentrations. Levels of major lower brominated PBDEs appear to have declined in
      fish fillets by 46-74% between 2006/07 and 2012. Although PBDE in existing
      consumer items will remain in-use for a while, it will likely not result in
      appreciable accumulation of PBDEs in fish. Based on an overall assessment,
      regular monitoring of PBDEs in Great Lake fish can be replaced with targeted
      surveillance and focus can be shifted to other in-use flame retardants.

PMID- 27865118
TI  - Dienogest reduces proliferation, NGF expression and nerve fiber density in human
      adenomyosis.
AB  - OBJECTIVES: To evaluate the in vivo effect of dienogest on proliferation,
      apoptosis, aromatase expression, vascular density, nerve growth factor (NGF)
      expression and nerve fiber density in human adenomyosis tissue. STUDY DESIGN:
      Twelve women who underwent hysterectomy for adenomyosis were enrolled. Six
      patients received dienogest treatment prior to hysterectomy (dienogest group),
      and age-matched six patients who had not received any hormonal treatment for >=3
      months before surgery (control group). Cell proliferation, vascular and nerve
      fiber density in adenomyosis tissue were evaluated by staining for Ki67, von
      Willebrand factor and PGP9.5, respectively. Apoptosis was detected using the
      TUNEL assay. The expression aromatase and NGF were evaluated by staining for
      corresponding antibodies. RESULTS: The proportion of Ki67 positive epithelial
      cells was significantly lower in samples from dienogest-treated patients in
      comparison with controls (p<0.05). The density of blood vessels in adenomyosis
      was marginally lower in the dienogest group in comparison with controls but
      statistical significance was not reached (p=0.07). The intensity of NGF
      expression and the density of nerve fibers were significantly lower in the
      dienogest group compared with controls (p<0.05 for both). CONCLUSION: This study
      demonstrates that adenomyosis, taken from patients treated with dienogest, shows
      remarkable histological features, such as reductions in proliferation, NGF
      expression and nerve fiber density. These findings indicate the impact of
      dienogest on local histological events, and explains its therapeutic effect on
      adenomyosis.

PMID- 27865121
TI  - Physiological responses of a population of Sargassum vulgare (Phaeophyceae) to
      high pCO2/low pH: implications for its long-term distribution.
AB  - Ocean Acidification (OA) is likely to affect macroalgal diversity in the future
      with species-specific responses shaping macroalgal communities. In this
      framework, it is important to focus research on the photosynthetic response of
      habitat-forming species which have an important structural and functional role in
      coastal ecosystems. Most of the studies on the impacts of OA involve short-term
      laboratory or micro/mesocosm experiments. It is more challenging to assess the
      adaptive responses of macroalgal community to decreasing ocean pH over long-term
      periods, as they represent the basis of trophic dynamics in marine environments.
      This work aims to study the physiological traits of a population of Sargassum
      vulgare that lives naturally in the high pCO2 vents system in Ischia (Italy), in
      order to predict the species behaviour in a possible OA future scenario. With
      this purpose, the photosynthetic performance of S. vulgare was studied in a wild,
      natural population living at low pH (6.7) as well as in a population transplanted
      from native (6.7) to ambient pH (8.1) for three weeks. The main results show that
      the photochemical activity and Rubisco expression decreased by 30% after
      transplanting, whereas the non-photochemical dissipation mechanisms and the
      photosynthetic pigment content increased by 50% and 40% respectively, in order to
      compensate for the decrease in photochemical efficiency at low pH. Our data
      indicated a stress condition for the S. vulgare population induced by pH
      variation, and therefore a reduced acclimation capability at different pH
      conditions. The decline of the PSII maximum quantum yield (Fv/Fm) and the
      increase of PARP enzyme activity in transplanted thalli further supported this
      hypothesis. The absence of the species at ambient pH conditions close to the vent
      system, as well as the differences in physiological traits, suggest a local
      adaptation of S. vulgare at pH6.7, through optimization of photosynthetic
      performance.

PMID- 27865122
TI  - Prolonged grief and post-traumatic stress among relatives of missing persons and
      homicidally bereaved individuals: A comparative study.
AB  - BACKGROUND: Traumatic loss (e.g., homicide) is associated with elevated prolonged
      grief disorder (PGD) and posttraumatic stress disorder (PTSD). Several studies
      comparing relatives of missing persons with homicidally bereaved individuals
      showed inconsistent results about the difference in PGD- and PTSD-levels between
      the groups. These studies were conducted in the context of armed conflict, which
      may confound the results. The current study aims to compare PGD- and PTSD-levels
      between the groups outside the context of armed conflict. METHODS: Relatives of
      long-term missing persons (n=134) and homicidally bereaved individuals (n=331)
      completed self-report measures of PGD and PTSD. Multilevel regression modelling
      was used to compare symptom scores between the groups. RESULTS: Homicidally
      bereaved individuals reported significantly higher levels of PGD (d=0.86) and
      PTSD (d=0.28) than relatives of missing persons, when taking relevant covariates
      (i.e., gender, time since loss, and kinship to the disappeared/deceased person)
      into account. LIMITATIONS: A limitation of this study is the use of self-report
      measures instead of clinical interviews. CONCLUSION: Prior studies among
      relatives of missing persons and homicidally bereaved individuals in the context
      of armed conflict may not be generalizable to similar samples outside these
      contexts. Future research is needed to further explore differences in bereavement
      related psychopathology between different groups and correlates and treatment of
      this psychopathology.

PMID- 27865125
TI  - Preceptors' conceptions of a peer learning model: A phenomenographic study.
AB  - BACKGROUND: During the past few years nurses precepting undergraduate nursing
      students have been put under greater pressure because of increased number of
      students admitted to the universities combined with a shortage of clinical
      placements. One solution is the preceptor model peer learning where two students
      are tutored by the same preceptor simultaneously. OBJECTIVES: The aim of this
      study was to describe the variation of registered nurses' conceptions of
      preceptorship in a peer learning model for undergraduate nursing students.
      DESIGN: The study used a qualitative descriptive design and a phenomenographic
      approach. SETTINGS: The interviews took place at somatic and psychiatric units at
      two different hospitals in southern Sweden. PARTICIPANTS: Twelve informants
      participated who had worked as registered nurses between 1-17years and acted as
      peer learning preceptors between 2month and 6years. METHODS: Each nurse was
      interviewed individually using a semi structured interview guide. Follow up
      questions were used to make the informants develop and deepen their answers.
      RESULTS: Four different descriptive categories emerged in the study: 1)
      Preceptorship in peer learning generates development and new perspectives 2)
      Preceptorship in peer learning enables student reflection and independence 3)
      Preceptorship in peer learning engenders insufficiency and stress 4)
      Preceptorship in peer learning requires education and support. CONCLUSIONS: The
      result of this study showed that preceptors conceived that peer learning enabled
      them to take a step back which gave them a new role and perspectives. The
      consequence was that the students could be more independent which saved time for
      some of the preceptors. However, some preceptors perceived insufficiency and
      stress while working with two students. It is also important to educate both
      students and preceptors to optimise the use of peer learning.

PMID- 27865124
TI  - The "killer cell story" in recurrent miscarriage: Association between activated
      peripheral lymphocytes and uterine natural killer cells.
AB  - Peripheral and uterine NK cells (pNK, uNK) can be distinguished according to
      their receptor expression. Recent studies indicate an association of elevated pNK
      and uNK with recurrent miscarriage (RM). This study aimed to analyze pNK and uNK
      in patients with RM and healthy controls. Out of n=590 RM patients screened
      according to a standard diagnostic protocol, n=268 couples with >=3 consecutive
      RM were identified. Subgroups consisted of n=151 primary RM (pRM), n=85 secondary
      RM (sRM), n=32 tertiary RM (tRM) and n=42 healthy controls. Finally, n=147
      idiopathic RM (iRM) and n=121 non-iRM patients were identified. Peripheral blood
      levels of CD45+CD3-CD56+CD16+ NK cells were determined in non-pregnant patients
      and controls in the mid-luteal phase by FACS. In n=129 RM patients a uterine
      biopsy was taken to evaluate CD56+ NK cells by immunohistochemistry. PRM showed
      higher absolute pNK than sRM (median/MUl (Q1;Q3): 234 (147;306) vs 176 (128;245),
      p=0.02). Further a trend towards higher pNK percentages in pRM was detected. UNK
      numbers did not differ between RM subgroups and did not correlate with pNK.
      However, the rate of highly elevated uNK was increased in iRM compared to non-iRM
      patients (p=0.04). Further, higher numbers of CD45+CD3-DR+ (p<0.01) and
      CD45+CD3+CD8+DR+ (p=0.04) peripheral lymphocytes were associated with higher uNK
      numbers. In conclusion, elevated pNK were present in pRM patients. Although pNK
      and uNK numbers did not correlate, the association between high CD45+CD3-DR+ and
      CD45+CD3+CD8+DR+ peripheral lymphocytes and uNK might indicate that activated NK,
      B and T cells provide cytokines for the differentiation of uNK.

PMID- 27865126
TI  - Crossing the canal: Looking beyond hernias - Spectrum of common, uncommon and
      atypical pathologies in the inguinal canal.
AB  - Inguinal canal can have diverse range of pathologies due to its complex anatomy
      and multiple different contents in the males and females. Imaging plays a
      dominant role in the appropriate diagnosis and management as inguinal pathologies
      have fairly similar clinical presentation with pain and swelling. Various
      pathologies in the inguinal region include congenital, infectious/inflammatory,
      vascular, neoplastic and iatrogenic. This paper gives an overview of the role of
      various modalities like Ultrasound, CT and MRI in the evaluation of inguinal
      pathologies.

PMID- 27865123
TI  - Decontamination of Bacillus spores adhered to iron and cement-mortar drinking
      water infrastructure in a model system using disinfectants.
AB  - Decontamination of Bacillus spores adhered to common drinking water
      infrastructure surfaces was evaluated using a variety of disinfectants. Corroded
      iron and cement-mortar lined iron represented the infrastructure surfaces, and
      were conditioned in a 23 m long, 15 cm diameter (75 ft long, 6 in diameter) pilot
      scale drinking water distribution pipe system. Decontamination was evaluated
      using increased water velocity (flushing) alone at 0.5 m s-1 (1.7 ft s-1), as
      well as free chlorine (5 and 25 mg L-1), monochloramine (25 mg L-1), chlorine
      dioxide (5 and 25 mg L-1), ozone (2.0 mg L-1), peracetic acid 25 mg L-1) and
      acidified nitrite (0.1 mol L-1 at pH 2 and 3), all followed by flushing at 0.3 m
      s-1 (1 ft s-1). Flushing alone reduced the adhered spores by 0.5 and 2.0 log10
      from iron and cement-mortar, respectively. Log10 reduction on corroded iron pipe
      wall coupons ranged from 1.0 to 2.9 at respective chlorine dioxide concentrations
      of 5 and 25 mg L-1, although spores were undetectable on the iron surface during
      disinfection at 25 mg L-1. Acidified nitrite (pH 2, 0.1 mol L-1) yielded no
      detectable spores on the iron surface during the flushing phase after
      disinfection. Chlorine dioxide was the best performing disinfectant with >3.0
      log10 removal from cement-mortar at 5 and 25 mg L-1. The data show that free
      chlorine, monochloramine, ozone and chlorine dioxide followed by flushing can
      reduce adhered spores by > 3.0 log10 on cement-mortar.

PMID- 27865127
TI  - Beef consumer segment profiles based on information source usage in Poland.
AB  - The main aim of this study was to identify market segments based on consumers'
      usage of information sources about beef and to investigate whether the use of
      information sources was associated with the type of information consumers were
      searching for, factors guiding their decision processes to buy beef and motives
      related to beef consumption. Data were collected in 2014 through a self
      administered survey of 501 regular beef consumers. Three distinct clusters were
      identified: Enthusiast (38.5%), Conservative (43.1%) and Ultra Conservative
      (18.4%). This study revealed that culinary and personal sources of information on
      beef were the most frequently used. Taste, perceived healthiness and suitability
      to prepare many dishes were reported as primary motives to eat beef. These
      results show that communication channels such as culinary programs and
      opportunities provided by the development of labelling systems to guarantee beef
      quality should be considered when developing policies and strategies to increase
      beef consumption in Poland.

PMID- 27865129
TI  - Laurdan emission study of the cholesterol-like effect of long-chain
      alkylresorcinols on the structure of dipalmitoylphosphocholine and sphingomyelin
      membranes.
AB  - Long-chain alkylresorcinols (ARs) are commonly found in plant and bacteria cells,
      and they exhibit a wide variety of biological effects, including antifungal,
      antitumor, and antiphrastic activities. The cholesterol (Chol)-like effect of ARs
      with hydrocarbon side-chain lengths ranging from C15 to C25 on the structure of
      pure and Chol-doped dipalmitoylphosphocholine (DPPC) and sphingomyelin (SM)
      membranes was investigated by Laurdan fluorescence spectroscopy. The Laurdan
      emission generalized polarization parameter was analyzed as a function of the
      temperature and excitation wavelength in DPPC (or SM)/Chol, DPPC (or SM)/AR, and
      DPPC/Chol/AR systems. It was found that AR incorporation into both DPPC and SM
      bilayers induces an increase in the temperature of the main lipid phase
      transition, similar to the effect of Chol molecule incorporation. The phase
      separation, lipid-chain ordering, and membrane hydration are discussed for the AR
      mixed membranes and compared with DPPC (or SM)/Chol membranes.

PMID- 27865128
TI  - The pleiotropic role of non-coding genes in development and cancer.
AB  - The expansive dimension of non-coding genes is by now a well-recognized feature
      of eukaryotes genomes. Over the past decades, in vitro functional studies and in
      vivo manipulation of non-coding genes through Genetically Engineered Mouse Models
      (GEMMs) have provided compelling evidence that almost every biological phenomenon
      is regulated, at some level, by non-coding RNA transcripts or by coding RNAs with
      non-coding functions. In this opinion article, we will discuss how recent
      discoveries in the field of non-coding RNAs are contributing to advance our
      understanding of evolution and organismal complexity and its relevance to human
      diseases.

PMID- 27865130
TI  - Effects of fatigue on lower limb, pelvis and trunk kinematics and muscle
      activation: Gender differences.
AB  - BACKGROUND: Muscle fatigue is associated with biomechanical changes that may lead
      to anterior cruciate ligament (ACL) injuries. Alterations in trunk and pelvis
      kinematics may also be involved in ACL injury. Although some studies have
      compared the effects of muscle fatigue on lower limb kinematics between men and
      women, little is known about its effects on pelvis and trunk kinematics. The aim
      of the study was to compare the effects of fatigue on lower limb, pelvis and
      trunk kinematics and muscle activation between men and women during landing.
      METHODS: The participants included forty healthy subjects. We performed kinematic
      analysis of the trunk, pelvis, hip and knee and muscle activation analysis of the
      gluteal muscles, vastus lateralis and biceps femoris, during a single-leg landing
      before and after fatigue. RESULTS: Men had greater trunk flexion than women after
      fatigue. After fatigue, a decrease in peak knee flexion and an increase in Gmax
      and BF activation were observed. CONCLUSION: The increase in the trunk flexion
      can decrease the anterior tibiofemoral shear force resulted from the lower knee
      flexion angle, thereby decreasing the stress on the ACL.

PMID- 27865131
TI  - Evaluation of cellular uptake, cytotoxicity and cellular ultrastructural effects
      of heteroleptic oxidovanadium(IV) complexes of salicylaldimines and polypyridyl
      ligands.
AB  - Searching for prospective vanadium-based drugs for cancer treatment, a new series
      of structurally related [VIVO(L-2H)(NN)] compounds (1-8) was developed. They
      include a double deprotonated salicylaldimine Schiff base ligand (L-2H) and
      different NN-polypyridyl co-ligands having DNA intercalating capacity. Compounds
      were characterized in solid state and in solution. EPR spectroscopy suggests that
      the NN ligands act as bidentate and bind through both nitrogen donor atoms in an
      axial-equatorial mode. The cytotoxicity was evaluated in human tumoral cells
      (ovarian A2780, breast MCF7, prostate PC3). The cytotoxic activity was dependent
      on type of cell and incubation time. At 24h PC3 cells presented low sensitivity,
      but at 72h all complexes showed high cytotoxic activity in all cells. Human
      kidney HEK293 and ovarian cisplatin resistant A2780cisR cells were also included
      to evaluate selectivity towards cancer cells and potency to overcome cisplatin
      resistance, respectively. Most complexes showed no detectable interaction with
      plasmid DNA, except 2 and 7 which depicted low ability to induce single strand
      breaks in supercoiled DNA. Based on the overall cytotoxic profile, complexes with
      2,2'-bipyridine and 1,10-phenanthroline ligands (1 and 2) were selected for
      further studies, which consisted on cellular distribution and ultrastructural
      analyses. In the A2780 cells both depicted different distribution profiles; the
      former accumulates mostly at the membrane and the latter in the cytoskeleton.
      Morphology of treated cells showed nuclear atypia and membrane alterations, more
      severe for 1. Complexes induce different cell death pathways, predominantly
      necrosis for 1 and apoptosis for 2. Complexes alternative mode of cell death
      motivates the possibility for further developments.

PMID- 27865132
TI  - A network approach to policy framing: A case study of the National Aboriginal and
      Torres Strait Islander Health Plan.
AB  - Aboriginal health policy in Australia represents a unique policy subsystem
      comprising a diverse network of Aboriginal-specific and "mainstream"
      organisations, often with competing interests. This paper describes the network
      structure of organisations attempting to influence national Aboriginal health
      policy and examines how the different subgroups within the network approached the
      policy discourse. Public submissions made as part of a policy development process
      for the National Aboriginal and Torres Strait Islander Health Plan were analysed
      using a novel combination of network analysis and qualitative framing analysis.
      Other organisational actors in the network in each submission were identified,
      and relationships between them determined; these were used to generate a network
      map depicting the ties between actors. A qualitative framing analysis was
      undertaken, using inductive coding of the policy discourses in the submissions.
      The frames were overlaid with the network map to identify the relationship
      between the structure of the network and the way in which organisations framed
      Aboriginal health problems. Aboriginal organisations were central to the network
      and strongly connected with each other. The network consisted of several densely
      connected subgroups, whose central nodes were closely connected to one another.
      Each subgroup deployed a particular policy frame, with a frame of "system
      dysfunction" also adopted by all but one subgroup. Analysis of submissions
      revealed that many of the stakeholders in Aboriginal health policy actors are
      connected to one another. These connections help to drive the policy discourse.
      The combination of network and framing analysis illuminates competing interests
      within a network, and can assist advocacy organisations to identify which network
      members are most influential.

PMID- 27865133
TI  - Rejoinder to Karen Lutfey Spencer.

PMID- 27865134
TI  - Polychromatic light (480-3400nm) similar to the terrestrial solar spectrum
      without its UV component in post-surgical immunorehabilitation of breast cancer
      patients.
AB  - To this day, two methods of phototherapy (PT) have been successfully used in post
      surgical immunorehabilitation of patients with breast cancer (BC): intravenous
      laser irradiation of the patients' blood and reinfusion of lympholeukosuspension
      of BC patients after single irradiation with HeNe laser. The objective of this
      pilot experimental study was to verify the effectiveness of the percutaneous use
      of polychromatic visible light combined with polychromatic infrared (pVIS+pIR)
      radiation similar to the major components of natural solar spectrum in post
      surgical management of BC patients. Patients with BC (adenocarcinoma) of I-II
      stages, n=19 who had undergone mastectomy, were divided into 2 groups. The
      control group of patients (n=8) underwent a conventional course of post-surgical
      rehabilitation and sham irradiation. Patients of the PT group (n=11) additionally
      received 7days of daily treatment with polychromatic light on the sacral area,
      D=15cm. The PT course began on the day after mastectomy (Bioptron-2 device;
      Switzerland, 480-3400nm, 95% polarization, 40mW/cm2, 24J/cm2). Mastectomy
      produced many changes in cellular and humoral immunity, which was recorded on the
      1st and 8th post-surgical days. The PT course resulted in a faster normalization
      of post-surgical leukocytosis and activation of cytotoxic CD8+ T-lymphocytes
      (Lym), reduced the elevated concentration in blood of immune complexes and in
      parallel promoted cytotoxic activity of CD16+/CD56+ NK-cells. The PT up-regulated
      the number of NK-cells in patients with its decrease on the 1st post-surgical day
      and prevented the decrease in the amount of monocytes, CD19+ B-Lym, CD3+ T-Lym,
      CD4+ T-helpers, activated CD3+/HLADR+ T-Lym, and the decrease of the phagocytotic
      capability of neutrophils. PT blocked the down-regulation of the IgM, IgA
      concentration and abnormally sharp increase of the proinflammatory cytokine IFN
      gamma content. Therefore, a 7-day course with polychromatic light prevented the
      development of immunosupression in the BC patients at the early post-mastectomy
      period.

PMID- 27865135
TI  - Applications of vitamin B6 cofactor pyridoxal 5'-phosphate and pyridoxal 5'
      phosphate crowned gold nanoparticles for optical sensing of metal ions.
AB  - Vitamin B6 cofactor pyridoxal 5'-phosphate (PLP) and PLP crowned gold
      nanoparticles (PLP-AuNPs) was applied for the optical chemosensing of metal ions
      in aqueous medium. PLP showed a visually detectable colour change from colourless
      to yellow and 'turn-off' fluorescence in the presence of Fe3+. The fluorescence
      intensity of PLP at 433nm was also blue-shifted and enhanced at 395nm upon
      addition of Al3+. When the PLP was functionalized over AuNPs surface, the wine
      red colour of PLP-AuNPs was turned to purplish-blue and the SPR band at ~525nm
      was red-shifted upon addition of Al3+, Cd2+ and Pb2+ due to the complexation
      induced aggregation of nanoparticles. The developed sensing systems exhibited
      good selectivity and specificity for the detected analytes (Fe3+, Al3+, Cd2+ and
      Pb2+).

PMID- 27865137
TI  - Calix[3]carbazole: A C3-symmetrical receptor for barium ion.
AB  - The binding ability of calix[3]carbazole (1) to metal ions has been investigated.
      It is found that 1 could serve as a non crown ether based, C3-symmetrical
      receptor for Ba2+ via the marriage of cation-pi and cation-dipole interactions.
      FID assay further illustrates that 1 could selectively interact with Ba2+ over
      Pd2+. A possible binding mechanism for [1-Ba2+] complex is proposed.

PMID- 27865136
TI  - pH-dependent absorption spectra of rhodopsin mutant E113Q: On the role of
      counterions and protein.
AB  - The absorption spectra of bovine rhodopsin mutant E113Q in solutions were
      investigated at the molecular level by using a hybrid quantum mechanics/molecular
      mechanics (QM/MM) method. The calculations suggest the mechanism of the
      absorption variations of E113Q at different pH values. The results indicate that
      the polarizations of the counterions in the vicinity of Schiff base under
      protonation and unprotonation states of the mutant E113Q would be a crucial
      factor to change the energy gap of the retinal to tune the absorption spectra.
      Glu-181 residue, which is close to the chromophore, cannot serve as the
      counterion of the protonated Schiff base of E113Q in dark state. Moreover, the
      results of the absorption maximum in mutant E113Q with the various anions (Cl-,
      Br-, I- and NO3-) manifested that the mutant E113Q could have the potential for
      use as a template of anion biosensors at visible wavelength.

PMID- 27865138
TI  - Young driver risky behaviour and predictors of crash risk in Australia, New
      Zealand and Colombia: Same but different?
AB  - Young drivers remain overrepresented in road crashes around the world, with road
      injury the leading cause of death among adolescents. In addition, the majority of
      road traffic crashes, fatalities and injuries occur in low- and middle-income
      countries. All young drivers are at risk due to a breadth of age- and
      inexperience-related factors; however it is well recognised that young drivers
      may also intentionally engage in risky driving behaviours which increase their
      crash risk. The aim of this paper is to examine the self-reported risky driving
      behaviour of young drivers in Australia, New Zealand (high-income countries), and
      Colombia (middle-income country), and to explore the utility of a crash risk
      assessment model in these three countries. Young drivers aged 16-25 years
      completed the Behaviour of Young Novice Drivers Scale (BYNDS), in addition to
      self-reporting crash involvement and driving offences. A hierarchical
      segmentation analysis via decision trees was used to study the relationship
      between self-reported crashes and risky driving. Young drivers in Colombia
      reported more risky driving than young drivers in New Zealand, and considerably
      more risky driving than young drivers in Australia. Significant differences among
      and across countries in individual BYNDS items were found, and 23.5% of all
      participants reported they had been involved in a road crash. Handheld mobile
      phone usage was the strongest predictor of crashes, followed by driving after
      drinking alcohol, and carrying friends as passengers. Country of origin predicted
      mobile phone usage, with New Zealand and Colombia grouped in the same decision
      tree branch which implies no significant differences in the behaviour between
      these countries. Despite cultural differences in licensing programs and
      enforcement, young drivers reported engaging in a similar breadth of risky
      behaviours. Road crashes were explained by mobile phone usage, drink driving and
      driving with passengers, suggesting interventions should target these three risk
      factors. Whilst New Zealand and Australia have implemented graduated driver
      licensing programs, are geographical neighbours, and are high-income countries,
      the finding that behaviours of young drivers in New Zealand and Colombia were
      more similar than those of young drivers in New Zealand and Australia merits
      further investigation.

PMID- 27865139
TI  - Real-world evaluation of the effectiveness of reversing camera and parking sensor
      technologies in preventing backover pedestrian injuries.
AB  - Backover injuries to pedestrians are a significant road safety issue, but their
      prevalence is underestimated as the majority of such injuries are often outside
      the scope of official road injury recording systems, which just focus on public
      roads. Based on experimental evidence, reversing cameras have been found to be
      effective in reducing the rate of collisions when reversing; the evidence for the
      effectiveness of reverse parking sensors has been mixed. The wide availability of
      these technologies in recent model vehicles provides impetus for real-world
      evaluations using crash data. A logistic model was fitted to data from crashes
      that occurred on public roads constituting 3172 pedestrian injuries in New
      Zealand and four Australian States to estimate the odds of backover injury
      (compared to other sorts of pedestrian injury crashes) for the different
      technology combinations fitted as standard equipment (both reversing cameras and
      sensors; just reversing cameras; just sensors; neither cameras nor sensors)
      controlling for vehicle type, jurisdiction, speed limit area and year of
      manufacture restricted to the range 2007-2013. Compared to vehicles without any
      of these technologies, reduced odds of backover injury were estimated for all
      three of these technology configurations: 0.59 (95% CI 0.39-0.88) for reversing
      cameras by themselves; 0.70 (95% CI 0.49-1.01) for both reversing cameras and
      sensors; 0.69 (95% CI 0.47-1.03) for reverse parking sensors by themselves. These
      findings are important as they are the first to our knowledge to present an
      assessment of real-world safety effectiveness of these technologies.

PMID- 27865140
TI  - Overcoming dynamic molecular heterogeneity in metastatic colorectal cancer:
      Multikinase inhibition with regorafenib and the case of rechallenge with anti
      EGFR.
AB  - In metastatic colorectal cancer (mCRC), fluorouracil-based combination therapy
      with oxaliplatin or irinotecan is the mainstay of first-line treatment. Patient
      survival has been significantly improved with the introduction of monoclonal
      antibodies against VEGF (bevacizumab), VEGFR2 (ramucirumab) or EGFR (cetuximab or
      panitumumab) in first- and second-line therapies. However, all patients treated
      with chemotherapy and targeted therapies will eventually relapse, and recently
      the emergence of alterations in EGFR, RAS, BRAF, ERB-B2, MET and possibly in
      other genes has been shown to jeopardize response to EGFR blockade. In
      chemorefractory patients, multikinase inhibition with regorafenib has proved to
      be effective and rechallenge with chemotherapy or anti-EGFR agents is empirically
      pursued. This review will critically discuss how the evolving knowledge of
      mechanisms of resistance driven by intratumoural dynamic molecular heterogeneity
      can impact on rational choice of treatments in this setting.

PMID- 27865142
TI  - Acute renal failure due to complete labial fusion: A case report.
AB  - Acute renal failure is characterized by rapidly disruption in kidney function and
      postrenal causes typically result from obstruction of urinary flow. Multiple
      etiologies were described for acute renal failure, but labial fusion in
      postmenopausal female is a quite rarely encountered pathology among postrenal
      causes. Only a few cases have been presented in postmenopausal women presenting
      with urinary retention. We present a case with acute renal failure due to
      complete labial fusion in a postmenopausal woman and its treatment.

PMID- 27865141
TI  - Fostering secure attachment in low- and middle-income countries: Suggestions for
      evidence-based interventions.
AB  - Children struggling with the effects of trauma in low- and middle-income
      countries (LMIC) face a substantial mental health resource gap that limits their
      opportunities for positive psychosocial development. Multidisciplinary
      interventions working to close this gap may benefit from incorporating an
      empirically supported treatment (EST) into their approach that targets a
      universal mechanism implicated in resilience, like attachment. ESTs should be
      selected based on their level of empirical support and cultural adaptability, and
      then modified on the basis of qualitative evaluations conducted with the local
      population and stakeholders. This paper will provide an overview of attachment as
      a mechanism of resilience, a critical analysis of existing attachment-based ESTs,
      and recommendations for overcoming EST implementation barriers in LMIC.

PMID- 27865143
TI  - The postauricular fasciocutaneous flap with an adipofascial extension: A case
      report.
AB  - INTRODUCTION: A complex defect on the anterior surface of the ear requires flap
      cover; such as the postauricular skin flap. The postauricular skin flap has never
      been used with an adipofascial extension. PRESENTATION OF CASE: A 5-year old boy
      was involved in a car accident resulting in an exposed cartilage of the upper
      part of the right ear. The defect was covered with a post-auricular
      fasciocutaneous flap with an adipofascial extension. The adipofascial part of the
      flap was covered with a skin graft. DISCUSSION: The adipofascial extension serves
      two purposes: Firstly, it allows easier primary closure of the donor site.
      Secondly, it is less bulky and hence it does not observe the definition of the
      ear cartilage. CONCLUSION: Our case is the first case reported in literature
      using the post-auricular fasciocutaneous flap with an adipofascial extension.

PMID- 27865144
TI  - Successful endovascular management of endoleak-like phenomenon following open
      abdominal aortic aneurysm repair.
AB  - INTRODUCTION: Endoleaks are a well-known complication after endovascular aortic
      repair. Type I endoleak-like phenomenon (also defined as a proximal
      pseudoaneurysm) post-open abdominal aortic aneurysm (AAA) repair is described as
      an anastomotic leak causing recurrent pressurization of the original aneurysm
      sac. It is rare but may result in aneurysmal sac rupture into the peritoneal
      cavity. REPORT: A 78-year-old man presented with a progressively enlarged
      aneurysmal sac due to proximal anastomotic degeneration of the proximal suture
      line associated with an outflow through a patent large lumbar vessel following a
      previous emergency open AAA repair. This was successfully treated using a
      combination coils and ethylene-vinyl alcohol copolymer. An Endoluminal tube stent
      graft was successfully deployed to seal the aortic anastomotic dehiscence.
      CONCLUSION: Endovascular treatment of an anastomotic dehiscence associated with a
      large outflow lumbar artery post-open AAA repair is feasible and safe.

PMID- 27865145
TI  - Rectal gastrointestinal stromal tumor with metastasis to the penis: Case report
      and review of literature.
AB  - We report the case of a 51-year-old gentleman with previously diagnosed
      gastrointestinal stromal tumor (GIST) of the rectum with metastasis to the penis.
      The patient underwent abdominoperineal resection of the primary tumor with
      negative margins and completed a three-year course of imatinib mesylate
      (Gleevec). Forty months after resection of his rectal tumor, the patient
      presented to his urologist with worsening testicular pain, mild lower urinary
      tract obstructive symptoms, and nocturia. A pelvic MRI revealed the presence of
      an ill-defined mass in the right perineum extending from the base of the penis to
      the penoscrotal junction. Biopsy of this mass was consistent with metastatic
      GIST. To our knowledge, this is the first report of metastatic GIST to the penis.

PMID- 27865146
TI  - A case report of successful diagnosis of a pulmonary nodule by a survey of
      oncogenic mutations; primary lung carcinoma or pulmonary metastasis?
AB  - INTRODUCTION: The number of patients diagnosed with solid carcinomas is
      increasing, and the most common site of metastasis is the lungs. It is often
      difficult to make a differential diagnosis between primary lung carcinoma and
      metastatic lung tumor in using histological examination and by determining their
      immunohistological status. PRESENTATION: A 64-years-old man presented with
      dyspnea with chest computed tomography (CT) findings of a pulmonary tumor, and
      afterwards suffered from a sudden bowel hemorrhaged due to colorectal carcinoma.
      The histological diagnosis of a pulmonary tumor was poorly differentiated
      adenocarcinoma. Both Thyroid transcription factor-1 (TTF-1) and Cytokeratin20
      (CK20) were immunohistologically negative. Of the some oncogenic mutations
      investigated, a neuroblastoma RAS viral oncogen homolog (NRAS) codon13 G13D
      mutation was detected in both the colorectal carcinoma and the pulmonary tumor
      tissue samples. Based on the result, the pulmonary tumor was diagnosed as a
      metastasis derived from colorectal carcinoma. DISCUSSION: Recently, examination
      of the oncogenes of solid carcinomas has been clinically investigated in primary
      lung caricnoma and in colorectal carcinomas. The clinical advantage of the
      oncogenic mutation survey is to identify the site, and the type, of amino acid
      change in detail. This case is a rare successful case of a survey of the
      oncogenes for giving a differential diagnosis. CONCLUSION: A survey of the
      oncogenic genes is very useful to make a differential diagnosis between primary
      lung carcinoma and metastatic lung tumor.

PMID- 27865147
TI  - Appendicitis as a rare cause of mechanical small-bowel obstruction: A literature
      review of case reports.
AB  - INTRODUCTION: Although bowel paralysis accompanying acute appendicitis is well
      known, mechanical bowel obstruction as a direct consequence of appendicitis
      remains a rare, but potentially life-threatening, acute abdomen. The aim of our
      literature review was to find all documented cases of this particular
      complication and compare them with our own case study. METHODS: We searched the
      PubMed database for relevant articles published from 1963 to 2015. The study
      included patients for whom direct links between appendicitis and strangulation of
      the terminal ileum were found, and for which the disease course had been
      documented in detail. The study also included our own case report since it met
      the inclusion criteria. A total of 190 articles were examined with a final yield
      of 17 case reports from 13 articles. RESULTS: 17 patients (11 men and 6 women),
      with a mean age of 48+/-23.9years, met the inclusion criteria. The average period
      between symptom onset and surgery was 3.4+/-3.7 days. Symptoms of the disease
      were consistent with small-bowel obstruction. Treatment included simple
      appendectomy (n=7), possibly supplemented by segmental resection (n=5), followed
      by ileocecal resection (n=4), and one case that required a right-sided
      hemicolectomy (n=1). CONCLUSION: We found mechanical bowel obstruction directly
      related to appendiceal inflammation to be extremely rare, and relatively few
      individual cases involving this potentially life-threatening complication have
      been documented in the literature. Clinical signs of the disease are variable,
      non-uniform, and consistent with symptoms of small-bowel obstruction during their
      progression.

PMID- 27865148
TI  - Plasma adrenomedullin in critically ill patients with sepsis after major surgery:
      A pilot study.
AB  - PURPOSE: Adrenomedullin is released by different tissues in hypoxia, oxidative
      stress, and inflammation and is found in general and medical patients and,
      recently, in sepsis patients in emergency departments. The aim of this study was
      to evaluate biologically active adrenomedullin that mirrors directly the active
      peptide levels in plasma of surgical intensive care unit (ICU) patients with
      sepsis. MATERIALS AND METHODS: In this single-center observational pilot trial,
      42 ICU patients with sepsis and 14 patients after major surgery were included
      after sepsis diagnosis or ICU admission. RESULTS: Patients (66% male) were 70
      (median) (interquartile range [IQR], 61-77]) years old and had a body mass index
      of 26.2 (24.2-29.4) kg/m2. The ICU and hospital length of stay was 8 (1-22) and
      17 (8-21) days, respectively. Eight patients had sepsis, 19 developed severe
      sepsis, and 15 suffered from septic shock. Adrenomedullin increased with severity
      (sepsis: 25.8 pg/mL [IQR 20.3-40.2], severe sepsis: 84.2 pg/mL [IQR 42.7-118.5],
      septic shock: 119.7 pg/mL [IQR 83.8-172.6]; P<.0001). Higher adrenomedullin was
      associated with poor 90-day outcomes (P=.019) and more frequent vasopressor use
      (P=.001). CONCLUSIONS: This is the first study investigating adrenomedullin in
      patients with sepsis following major surgery. Higher adrenomedullin on admission
      is associated with increased vasopressor need and mortality after 90 days. Thus,
      adrenomedullin may be a useful additional parameter in surgical patients with
      sepsis.

PMID- 27865149
TI  - Traceable measurement and imaging of the complex permittivity of a multiphase
      mineral specimen at micron scales using a microwave microscope.
AB  - This paper describes traceable measurements of the dielectric permittivity and
      loss tangent of a multiphase material (particulate rock set in epoxy) at micron
      scales using a resonant Near-Field Scanning Microwave Microscope (NSMM) at
      1.2GHz. Calibration and extraction of the permittivity and loss tangent is via an
      image charge analysis which has been modified by the use of the complex frequency
      to make it applicable for high loss materials. The results presented are obtained
      using a spherical probe tip, 0.1mm in diameter, and also a conical probe tip with
      a rounded end 0.01mm in diameter, which allows imaging with higher resolution
      (~10um). The microscope is calibrated using approach-curve data over a restricted
      range of gaps (typically between 1% and 10% of tip diameter) as this is found to
      give the best measurement accuracy. For both tips the uncertainty of scanned
      measurements of permittivity is estimated to be+/-10% (at coverage factor k=2)
      for permittivity ?10. Loss tangent can be resolved to approximately 0.001.
      Subject to this limit, the uncertainty of loss tangent measurements is estimated
      to be+/-20% (at k=2). The reported measurements inform studies of how microwave
      energy interacts with multiphase materials containing microwave absorbent phases.

PMID- 27865150
TI  - Event-level analysis of alcohol consumption and condom use in partnership
      contexts among men who have sex with men and transgender women in Lima, Peru.
AB  - BACKGROUND: We explored the association between alcohol use and condomless
      receptive (CRAI) and insertive (CIAI) anal intercourse within partnership
      contexts of men who have sex with men (MSM) and transgender women (TGW) in Lima,
      Peru. METHODS: From 2012-2014, we surveyed men and TGW (n=1607) who reported anal
      intercourse with >=1 male or TGW. Alcohol use with up to 3 sexual partners during
      the prior 90days was evaluated. Bivariate and multivariate analyses used
      generalized estimating equations to assess event-level associations between
      alcohol use, CRAI, CIAI, and partnership characteristics while adjusting for
      participant clustering from multiple partners. RESULTS: Of 4774 sexual
      partnerships reported, 48% were casual, 34% primary, 10% anonymous, and 8%
      commercial. Alcohol use preceding sex was significantly (p<0.05) associated with
      CRAI (PR=1.26) and CIAI (PR=1.37). Partnership characteristics significantly
      associated with alcohol use included commercial sex work (PR=2.21) and trended
      (p<0.10) towards alcohol use with casual (PR=1.16), transgender (PR=1.48), and
      moderno ("versatile"; PR=1.17) partners. CRAI and CIAI were more common among
      participants who reported knowing they (PR=1.52; PR=1.41, respectively) or their
      partner (PR=1.47; PR=1.44, respectively) was HIV-uninfected. Yet, only CIAI
      (PR=1.42) was more commonly reported with known HIV-infected partners.
      Participants who drank alcohol prior to sex were less likely to know their
      partner's HIV serostatus. CONCLUSIONS: Alcohol use prior to intercourse was
      associated with CRAI and CIAI, varied by partnership type, and may impair
      knowledge of partner HIV serostatus. Detailed knowledge of alcohol use within
      partner-specific contexts is essential for informing condom-based and alternative
      HIV prevention strategies for MSM and TGW in Peru.

PMID- 27865151
TI  - Effects of the benzodiazepine GABAA alpha1-preferring antagonist 3-isopropoxy
      beta-carboline hydrochloride (3-ISOPBC) on alcohol seeking and self
      administration in baboons.
AB  - BACKGROUND: The major inhibitory neurotransmitter, gamma-aminobutyric acid
      (GABA), modulates many of the behavioral effects of alcohol, including sedation,
      tolerance, and withdrawal. The alpha1 subunit of the benzodiazepine GABAA
      receptor is the most widely expressed alpha subunit in the brain, and has been
      implicated in the reinforcing- and abuse-related effects of alcohol. The aim of
      the present study was to examine whether treatment with a benzodiazepine GABAA
      alpha1-preferring ligand, 3-isopropoxy-beta-carboline hydrochloride (3-ISOPBC),
      selectively decreases alcohol seeking and consumption. METHODS: Eight baboons
      self-administered alcohol (4% w/v; n=5; alcohol group) or a non-alcoholic
      beverage (n=3; control group) in Component 3 of a chained schedule of
      reinforcement. Responses in Component 2 provided indices of motivation to drink
      (seeking). Doses of 3-ISOPBC (5.0-30.0mg/kg) and vehicle were administered before
      drinking sessions under both acute and chronic (5day) conditions. RESULTS:
      Chronic, and not acute, administration of 3-ISOPBC significantly decreased self
      administration responses, g/kg alcohol consumed, and the number of drinks in and
      duration of the first drinking bout in the alcohol group. In the control group,
      chronic administration of 3-ISOPBC did not significantly decrease any of these
      measures at any of the doses. CONCLUSIONS: The GABAA alpha1-preferring ligand 3
      ISOPBC may have therapeutic potential in the treatment of alcohol use disorder
      due to its ability to selectively reduce alcohol use.

PMID- 27865153
TI  - Efficient multi-scale 3D CNN with fully connected CRF for accurate brain lesion
      segmentation.
AB  - We propose a dual pathway, 11-layers deep, three-dimensional Convolutional Neural
      Network for the challenging task of brain lesion segmentation. The devised
      architecture is the result of an in-depth analysis of the limitations of current
      networks proposed for similar applications. To overcome the computational burden
      of processing 3D medical scans, we have devised an efficient and effective dense
      training scheme which joins the processing of adjacent image patches into one
      pass through the network while automatically adapting to the inherent class
      imbalance present in the data. Further, we analyze the development of deeper,
      thus more discriminative 3D CNNs. In order to incorporate both local and larger
      contextual information, we employ a dual pathway architecture that processes the
      input images at multiple scales simultaneously. For post-processing of the
      network's soft segmentation, we use a 3D fully connected Conditional Random Field
      which effectively removes false positives. Our pipeline is extensively evaluated
      on three challenging tasks of lesion segmentation in multi-channel MRI patient
      data with traumatic brain injuries, brain tumours, and ischemic stroke. We
      improve on the state-of-the-art for all three applications, with top ranking
      performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is
      computationally efficient, which allows its adoption in a variety of research and
      clinical settings. The source code of our implementation is made publicly
      available.

PMID- 27865154
TI  - A narrow bimalleolar width is a risk factor for ankle inversion injury in male
      military recruits: A prospective study.
AB  - BACKGROUND: Ankle inversion injuries are one of the most common and burdensome
      injuries in athletic populations. Research that prospectively identifies
      characteristics associated with this injury is lacking. This prospective study
      compared baseline anthropometric and biomechanical gait characteristics of
      military recruits who sustained an ankle inversion injury during training, with
      those who remained injury-free. METHODS: Bilateral plantar pressure and three
      dimensional lower limb kinematics were recorded in 1065 male, injury-free
      military recruits, during barefoot running. Injuries that occurred during the 32
      week recruit training programme were subsequently recorded. Data were compared
      between recruits who sustained an ankle inversion injury during training (n=27)
      and a sample (n=120) of those who completed training injury-free. A logistic
      regression analysis was used to identify risk factors for this injury. FINDINGS:
      A narrower bimalleolar width and an earlier peak pressure under the fifth
      metatarsal were predictors of ankle inversion injury. Those who sustained an
      ankle inversion injury also had a lower body mass, body mass index, and a smaller
      calf girth than those who completed training injury-free. INTERPRETATION:
      Anthropometric and dynamic gait characteristics have been identified that may
      predispose recruits to an ankle inversion injury during Royal Marine recruit
      training, allowing identification of recruits at higher risk at the start of
      training.

PMID- 27865155
TI  - Intuitive biological thought: Developmental changes and effects of biology
      education in late adolescence.
AB  - A large body of cognitive research has shown that people intuitively and
      effortlessly reason about the biological world in complex and systematic ways. We
      addressed two questions about the nature of intuitive biological reasoning: How
      does intuitive biological thinking change during adolescence and early adulthood?
      How does increasing biology education influence intuitive biological thinking? To
      do so, we developed a battery of measures to systematically test three components
      of intuitive biological thought: anthropocentric thinking, teleological thinking
      and essentialist thinking, and tested 8th graders and university students (both
      biology majors, and non-biology majors). Results reveal clear evidence of
      persistent intuitive reasoning among all populations studied, consistent but
      surprisingly small differences between 8th graders and college students on
      measures of intuitive biological thought, and consistent but again surprisingly
      small influence of increasing biology education on intuitive biological
      reasoning. Results speak to the persistence of intuitive reasoning, the
      importance of taking intuitive knowledge into account in science classrooms, and
      the necessity of interdisciplinary research to advance biology education. Further
      studies are necessary to investigate how cultural context and continued
      acquisition of expertise impact intuitive biology thinking.

PMID- 27865156
TI  - An unusual case of murder-suicide: The importance of studying knots.
AB  - An atypical murder-suicide that involved a married couple over 80 years of age
      was investigated at the Institute of Legal Medicine of the University of Chieti
      Pescara and is presented and discussed here. The whole story allows us to
      confront the difficulties involved in the discovery of a dead body in water when
      the circumstantial evidence does not allow any unique interpretation of the
      facts. The atypical and misleading element appeared to be how the body of the man
      was tied, with the interpretation inclined towards a homicidal manner of death.
      It was only by combining the contributions of each of the findings that emerged
      during the course of the autopsy with the circumstantial evidence from the site
      inspection that it was possible to reach resolution of this case, which was then
      identified as a murder-suicide.

PMID- 27865152
TI  - Psychoactive medications and disengagement from office based opioid treatment
      (obot) with buprenorphine.
AB  - BACKGROUND: The prevalence of psychoactive medications (PAMs) use in patients
      enrolled in Office Based Opioid Treatment (OBOT) and its association with
      engagement in this care is largely unknown. OBJECTIVE: To describe the use of
      PAMs, including those medications with emerging evidence of misuse ("emerging
      PAMs" - gabapentin, clonidine and promethazine) among patients on buprenorphine,
      and its association with disengagement from OBOT. METHODS: This is a
      retrospective cohort study of adults on buprenorphine from January 2002 to
      February 2014. The association between use of PAMs and 6-month disengagement from
      OBOT was examined using multivariable logistic regression models. A secondary
      analysis exploring time-to-disengagement was conducted using Cox regression
      models. RESULTS: At OBOT entry, 43% of patients (562/1308) were prescribed any
      PAM; including 17% (223/1308) on an emerging PAM. In separate adjusted analyses,
      neither the presence of any PAM (adjusted odds ratio [AOR] 1.07, 95% CI [0.78,
      1.46]) nor an emerging PAM (AOR 1.28 [0.95, 1.74]) was significantly associated
      with 6-month disengagement. The results were similar for the Cox model (any PAM
      (adjusted hazard ratio [AHR] 1.16, 95% CI [1.00, 1.36]), emerging PAM (AHR 1.18
      [0.98, 1.41])). Exploratory analyses suggested gabapentin (AHR 1.30 [1.05-1.62])
      and clonidine (AHR 1.33 [1.01-1.73]) specifically, may be associated with an
      overall shorter time to disengagement. CONCLUSIONS: Psychoactive medication use
      is common among patients in buprenorphine treatment. No significant association
      was found between the presence of any psychoactive medications, including
      medications with emerging evidence of misuse, and 6-month disengagement from
      buprenorphine treatment.

PMID- 27865158
TI  - Increasing cAMP levels of preadipocytes by cyanidin-3-glucoside treatment induces
      the formation of beige phenotypes in 3T3-L1 adipocytes.
AB  - Obesity is a serious health problem and a major risk factor for the onset of
      several diseases such as heart disease, diabetes, stroke and cancer. The
      conversion of white adipocytes to brown-like adipocytes, also called beige or
      brite adipocytes, by pharmacological and dietary compounds has gained attention
      as an effective treatment for obesity. Cyanidin-3-glucoside (Cy3G), a
      polyphenolic compound contained in black soybean, blueberry and grape, has
      several antiobesity effects. However, there are no reports on the role of Cy3G in
      the induction of differentiation of preadipocytes to beige adipocytes and
      corresponding phenotypes. Here, the formation of beige adipocyte phenotypes
      following treatment with Cy3G was evaluated using 3T3-L1 adipocytes. Cy3G induced
      phenotypic changes to white adipocytes, such as increased multilocular lipid
      droplets and mitochondrial content. Additionally, the expression of mitochondrial
      genes (TFAM, SOD2, UCP-1 and UCP-2), UCP-1 protein and beige adipocyte markers
      (CITED1 and TBX1) in 3T3-L1 adipocytes was increased by Cy3G. Furthermore, Cy3G
      promoted preadipocyte differentiation by up-regulating of C/EBPbeta through the
      elevation of the intracellular cAMP levels. These results indicated that Cy3G
      elevates the intracellular cAMP levels, which induces beige adipocyte phenotypes.
      This is the first report on the effect of Cy3G on induction of differentiation of
      preadipocytes into beige adipocyte phenotypes.

PMID- 27865157
TI  - Allegations of maltreatment in custody.
AB  - BACKGROUND: Maltreatment in custody overlaps with torture. Concerned governments
      avoid informing. These governments withhold information and try to impose
      definitions. Therefore, reports often cannot be verified, with the consequence
      being classified as "allegation". The misery of a victim influences the
      recording. Engaged parties modify their reporting according to their intention.
      The difficulty to verify reports and the position of governments affects the
      perception and in consequence the presentation. METHODS: Corporeal effects of
      maltreatment in custody are described. They rely on personal observations, on
      cases treated in the rehabilitations centres for victims of torture, and personal
      collections of colleagues. Therefore the material is selective. RESULTS: One can
      differentiate between not life-threatening maltreatment (with or without
      mutilation), life-threatening maltreatment, and maltreatment meant to kill.
      Examples are described. The possibilities of diagnostic imaging are mentioned.
      The limits of the given overview are pointed out. CONCLUSION: Knowing the
      possible forms is the basis to recognize allegations. Diagnostic imaging can
      prove maltreatment in rare cases, only. Reports and observations of maltreatment
      in custody create emotions. Governments and their organisation react, they
      withhold information and impose definitions. On the other hand, engaged parties
      insist that the misery of the victim has priority over the objective description.
      These positions influence and modify the perception and the use of allegations of
      maltreatment in custody.

PMID- 27865159
TI  - Dietary glutamine supplementation enhances endothelial progenitor cell
      mobilization in streptozotocin-induced diabetic mice subjected to limb ischemia.
AB  - Diabetes is a metabolic disorder with increased risk of vascular diseases. Tissue
      ischemia may occur with diabetic vascular complications. Bone marrow-derived
      endothelial progenitor cells (EPCs) constitute a reparative response to ischemic
      injury. This study investigated the effects of oral glutamine (GLN)
      supplementation on circulating EPC mobilization and expression of tissue EPC
      releasing markers in diabetic mice subjected to limb ischemia. Diabetes was
      induced by a daily intraperitoneal injection of streptozotocin for 5 days.
      Diabetic mice were divided into 2 nonischemic groups and 6 ischemic groups. One
      of the nonischemic and 3 ischemic groups were fed the control diet, while the
      remaining 4 groups received diets with identical components except that part of
      the casein was replaced by GLN. The respective diets were fed to the mice for 3
      weeks, and then the nonischemic mice were sacrificed. Unilateral hindlimb
      ischemia was created in the ischemic groups, and mice were sacrificed at 1, 7 or
      21 days after ischemia. Their blood and ischemic muscle tissues were collected
      for further analyses. Results showed that plasma matrix metallopeptidase (MMP)-9
      and the circulating EPC percentage increased after limb ischemia in a diabetic
      condition. Compared to groups without GLN, GLN supplementation up-regulated
      plasma stromal cell-derived factor (SDF)-1 and muscle MMP-9, SDF-1, hypoxia
      inducible factor-1 and vascular endothelial growth factor gene expression. The
      CD31-immunoreactive intensities were also higher in the ischemic limb. These
      findings suggest that GLN supplementation enhanced circulating EPC mobilization
      that may promote endothelium repair at ischemic tissue in diabetic mice subjected
      to limb ischemia.

PMID- 27865160
TI  - Aetiological relationships between factors associated with postnatal traumatic
      symptoms among Japanese primiparas and multiparas: A longitudinal study.
AB  - OBJECTIVE: this study aims to identify the aetiological relationships of
      psychosocial factors in postnatal traumatic symptoms among Japanese primiparas
      and multiparas. DESIGN: a longitudinal, observational survey. SETTING:
      participants were recruited at three institutions in Tokyo, Japan between April
      2013 and May 2014. Questionnaires were distributed to 464 Japanese women in late
      pregnancy (> 32 gestational weeks, Time 1), on the third day (Time 2) and one
      month (Time 3) postpartum. MEASUREMENTS: The Japanese Wijma Delivery
      Expectancy/Experience Questionnaire (JW-DEQ) version A was used to measure
      antenatal fear of childbirth and social support, while the Impact of Event Scale
      Revised (IES-R) measured traumatic stress symptoms due to childbirth. FINDINGS:
      of the 464 recruited, 427 (92%) completed questionnaires at Time 1, 358 (77%)
      completed at Time 2, and 248 (53%) completed at Time 3. Total 238 (51%) were
      analysed. A higher educational level has been identified in analysed group
      (p=0.021) Structural equation modelling was conducted separately for primiparas
      and multiparas and exhibited a good fit. In both groups antenatal fear of
      childbirth predicted Time 2 postnatal traumatic symptoms (beta=0.33-0.54, p=0.002
      0.007). Antenatal fear of childbirth was associated with a history of mental
      illness (beta=0.23, p=0.026) and lower annual income (beta =-0.24, p=0.018).
      Among multiparas, lower satisfaction with a previous delivery was related to
      antenatal fear of childbirth (beta =-0.28, p < 0.001). KEY CONCLUSIONS: antenatal
      fear of childbirth was a significant predictor of traumatic stress symptoms after
      childbirth among both primiparous and multiparous women. Fear of childbirth was
      predicted by a history of mental illness and lower annual income for primiparous
      women, whereas previous birth experiences were central to multiparous women.
      IMPLICATION FOR PRACTICE: the association between antenatal fear of childbirth
      and postnatal traumatic symptoms indicates the necessity of antenatal care. It
      may be important to take account of the background of primiparous women, such as
      a history of mental illness and their attitude towards the upcoming birth. For
      multiparous women, focusing on and helping them to view their previous birth
      experiences in a more positive light are vital tasks for midwives.

PMID- 27865161
TI  - Experiences of student midwives learning and working abroad in Europe: The value
      of an Erasmus undergraduate midwifery education programme.
AB  - BACKGROUND: universities in the United Kingdom are being challenged to modify
      policies and curricula that reflect the changing global reality through
      internationalisation. An aspect of internationalisation is study abroad which the
      European Commission Erasmus exchange programme is just one means of addressing
      this. OBJECTIVE: to explore the experiences of student midwives who are engaged
      in the Erasmus exchange programme and the effect it has on their learning and
      working in an international context. DESIGN: approval for the small
      phenomenological cohort study was obtained from two participating universities:
      the University of Malta and University of Nottingham. Data were collected from 13
      student midwives from a total of five cohorts in the form of diaries to explore
      their experiences of learning and working in another country. Thematic analysis
      supported by Computer-Assisted Qualitative Data Analysis Software was used to
      identify five recurrent themes emerging from the data: the findings of which have
      served further in developing this programme. FINDINGS: students valued the
      opportunity of undertaking study and midwifery practice in another culture and
      healthcare system, extending their knowledge and development of clinical
      competence and confidence. For some, this was the first time outside of their
      home country and adaptation to a new environment took time. Support from their
      contemporaries, lecturers and midwife mentors however, was overwhelmingly
      positive, enabling the students to feel 'part of the local university / midwifery
      team' By the end of the programme, the students recognised that they had become
      more independent and felt empowered to facilitate developments in practice when
      they returned home. IMPLICATIONS FOR EDUCATION / PRACTICE: this innovative
      development embracing internationalisation within the curricula has the potential
      to increase students' employability and further study within Europe and beyond.
      It can be used as a vehicle to share best practice within an international
      context, ultimately making a difference to the quality of care childbearing
      women, their babies and families experience worldwide.

PMID- 27865162
TI  - Irradiation-induced secretion of BMP4 by marrow cells causes marrow adipogenesis
      post-myelosuppression.
AB  - Pre-transplant myeloablation is associated with marrow adipogenesis, resulting in
      delayed engraftment of hematopoietic stem cells (HSCs). This is strongly
      undesirable, especially when the donor HSCs are fewer in numbers or have
      compromised functionality. The molecular mechanisms behind irradiation-induced
      marrow adipogenesis have not been extensively investigated. Here we show that
      bone marrow (BM) cells, especially T-cells and stromal cells, express and secrete
      copious amounts of BMP4 in response to irradiation, which causes the bone marrow
      stromal cells to commit to adipocyte lineage, thereby contributing to an increase
      in bone marrow adipogenesis. We further demonstrate that Simvastatin inhibits the
      BMP4-mediated adipogenic commitment of marrow stromal cells by inhibiting Ppar
      gamma expression. Importantly, Simvastatin does not prevent BMP4 secretion by the
      BM cells, and thus does not interfere with its salutary role in post-transplant
      hematopoietic regeneration. Our data identify previously unknown mechanisms
      operative in marrow adipogenesis post-myeloablation. They also reveal the
      molecular mechanisms behind the advantage of using Simvastatin as a niche
      targeting agent to improve HSC engraftment.

PMID- 27865163
TI  - Evaluation of patients with type 2 diabetes mellitus receiving treatment during
      the pre-diabetes period: Is early treatment associated with improved outcomes?
AB  - AIM: This study evaluates the association of pretreatment with oral antidiabetics
      (OADs) on clinical outcomes and health resource utilization among commercially
      insured type II diabetes mellitus (T2DM) patients in the United States. METHODS:
      Using administrative data (Truven MarketScan(r) Research Databases), patients
      diagnosed with T2DM between 2007 and 2014 with ?6months continuous enrolment pre-
      and post-diagnosis were evaluated. Pretreatment was defined as OAD use at least
      3months prior to T2DM diagnosis. Time-to-insulin initiation and healthcare costs
      were compared by OAD pretreatment status. RESULTS: Of the 866,605 patients
      studied, 241,856 (27.9%) were pretreated prior to T2DM diagnosis. Mean follow-up
      was 2.9years for pretreatment and 3.1years for those without pretreatment.
      Monthly diabetes-related pharmacy costs were significantly higher among
      pretreated patients ($66 versus $36, p<0.0001), as were overall monthly pharmacy
      costs ($255 versus $198, p<0.0001). Pretreated patients had lower mean monthly
      costs, both total ($625 versus $671, p<0.0001) and diabetes-related ($207 versus
      $214, p=0.0012). After multivariable adjustment, mean monthly diabetes-related
      total healthcare costs were higher among pretreated patients (+$60) but total all
      cause monthly healthcare costs were significantly lower (-$354) (both p<0.05).
      Pretreatment was associated with a lower insulin initiation probability for
      2years, after which probability was similar; the adjusted hazard ratio for
      pretreatment in a time-to-insulin model was 0.96 (95% CI, 0.94-0.97).
      CONCLUSIONS: Pretreatment with OADs is associated with a modest delay in
      initiating insulin therapy and lower total healthcare costs. The clinical and
      pharmacoeconomic benefits of pretreatment should be elucidated in a prospective
      study.

PMID- 27865164
TI  - Metformin improves lipid metabolism disorders through reducing the expression of
      microsomal triglyceride transfer protein in OLETF rats.
AB  - OBJECTIVE: This study aimed to investigate the role of MTP on lipid metabolism
      disorders in insulin-resistant rats and the potential mechanism through which
      metformin can improve lipid metabolism disorders. METHODS: 30 OLETF rats served
      as research subjects and 18 LETO rats of the same strain served as the control
      group (LETO group). After the first oral glucose tolerance test (at 8-week-old),
      6 rats were randomly killed from each group. The remaining 24 OLETF rats were
      randomly divided into untreated group (OLETF group) and treated group (OLETF/M
      group, cured with metformin). By the end of the 10th and 20th week of treatment,
      MTP in the liver was measured for all rats in the study. RESULTS: All OLETF rats
      exhibited diabetic phenotypes at 18-week-old, with their triglyceride level
      higher than in LETO rats at the same age. In OLETF rats, MTP level in the liver
      was higher than in LETO rats at 18-week-old, and the difference was significant
      at 28-week-old [(13.79+/-1.47) vs. (8.20+/-1.14), p<0.05]. Treatment with
      metformin for 20weeks decreased triglyceride [(1.06+/-0.23) vs. (2.20+/-0.62)
      mmol/L, p<0.05] and total cholesterol [(1.90+/-0.19) vs. (2.36+/-0.14) mmol/L,
      p<0.05] in OLETF rats. Metformin also decreased MTP level in the liver [(7.65+/
      1.31) vs. (13.79+/-1.47), p<0.01]. CONCLUSIONS: MTP may be associated with the
      lipid metabolism disorder in OLETF rats and metformin could improve lipid
      metabolism through reducing the expression of MTP.

PMID- 27865165
TI  - The utility of diabetes risk score items as predictors of incident type 2
      diabetes in Asian populations: An evidence-based review.
AB  - BACKGROUND: The prevalence of type 2 diabetes mellitus is rising, with many Asian
      countries featured in the top 10 countries with the highest numbers of persons
      with diabetes. Reliable diabetes risk scores enable the identification of
      individuals at risk of developing diabetes for early intervention. OBJECTIVES:
      This article aims to identify common risk factors in the risk scores with the
      highest discrimination; factors with the most influence on the risk score in
      Asian populations, and to propose a set of factors translatable to the multi
      ethnic Singapore population. METHODS: A systematic search of PubMed and EMBASE
      databases was conducted to identify studies published before August 2016 that
      developed risk prediction models for incident diabetes. RESULTS: 12 studies were
      identified. Risk scores that included laboratory measurements had better
      discrimination. Coefficient analysis showed fasting glucose and HbA1c having the
      greatest impact on the risk score. CONCLUSION: A proposed Asian risk score would
      include: family history of diabetes, age, gender, smoking status, body mass
      index, waist circumference, hypertension, fasting plasma glucose, HbA1c, HDL
      cholesterol and triglycerides. Future research is required on the influence of
      ethnicity in Singapore. The risk score may potentially be used to stratify
      individuals for enrolment into diabetes prevention programmes.

PMID- 27865166
TI  - Ethyl pyruvate inhibits the acetylation and release of HMGB1 via effects on
      SIRT1/STAT signaling in LPS-activated RAW264.7 cells and peritoneal macrophages.
AB  - High mobility group box 1 (HMGB1), a cytokine present in the late phase of
      sepsis, may be a potential target for the treatment of sepsis. For HMGB1 to be
      actively secreted from macrophages during infections, it must be post
      translationally modified. Although ethyl pyruvate (EP), a simple aliphatic ester
      derived from pyruvic acid, has been shown to inhibit the release of HMGB1 in
      lipopolysaccharide (LPS)-treated RAW 264.7 cells, the underlying mechanism(s) are
      not yet clear. We investigated the hypothesis that the upregulation of SIRT1 by
      EP might promote the deacetylation of HMGB1, which reduces HMGB1 release in LPS
      activated macrophages. Our results show that EP induced the expression of the
      SIRT1 protein in RAW264.7 cells and that it significantly inhibited the LPS
      induced acetylation of HMGB1. Transfection with a SIRT1-overexpressing vector
      resulted in a significant decrease in the acetylation of HMGB1 in LPS-activated
      RAW264.7 cells relative to control cells. The genetic ablation or the
      pharmacological inhibition of SIRT1 by sirtinol increased LPS-induced HMGB1
      acetylation. Moreover, EP inhibited the acetylation of HMGB1 in peritoneal
      macrophages treated with LPS. Interestingly, EP significantly reduced the LPS
      induced phosphorylation of STAT1, which was significantly reversed by siSIRT1
      transfection in RAW264.7 cells, indicating that SIRT1 negatively regulates the
      phosphorylation of STAT1. Overall, the results show that EP promotes the
      deacetylation of HMGB1 via the inhibition of STAT1 phosphorylation through the
      upregulation of SIRT1, which reduces HMGB1 release in LPS-activated RAW264.7
      cells. In conclusion, EP might be useful in the treatment of diseases that target
      HMGB1, such as sepsis.

PMID- 27865167
TI  - Accurate spectroscopic calculations of the 21 Lambda-S states and 42 Omega states
      of the SiB radical.
AB  - The potential energy curves were calculated for the 21 Lambda-S states, which
      were generated from the first two dissociation channels, Si(3Pg)+B(2Pu) and
      Si(1Dg)+B(2Pu), of the SiB radical. The potential energy curves were computed for
      the 42 Omega states, which arose from the 21 Lambda-S states. The calculations
      were done using the CASSCF method, which was followed by the icMRCI approach. Of
      these 21 Lambda-S states, the D4Sigma-, i2Sigma+, j2Pi, 52Pi, and 12Phi states
      had double wells. The D4Sigma-, a2Pi, A4Pi, e2Pi, j2Pi, 52Pi, h2Delta, and 12Phi
      states were inverted with the spin-orbit coupling effect taken into account. The
      32Delta state and the second wells of D4Sigma- and 12Phi states were weakly
      bound. Core-valence correlation correction, scalar relativistic correction and
      Davidson correction were included. The spectroscopic parameters were determined
      and the vibrational properties of some weakly-bound states were predicted. The
      spin-orbit coupling effect on the spectroscopic parameters was evaluated.
      Comparison with available experimental data shows that the methodology used is
      highly accurate for the SiB radical.

PMID- 27865168
TI  - Peristrut microhemorrhages: a possible cause of in-stent neoatherosclerosis?
AB  - BACKGROUND: In-stent neoatherosclerosis is characterized by the delayed
      appearance of markers of atheroma in the subintima, but the pathophysiology
      underlying this new disease entity remains unclear. METHODS AND RESULTS: We
      collected 20 human coronary artery stents by removal from explanted hearts. The
      mean duration of stent implantation was 34 months. In all samples,
      neoatherosclerosis was detected, particularly in peristrut areas. It consisted of
      foam cells and cholesterol clefts, with or without calcification, associated with
      neovascularization. Iron and glycophorin-A were present in peristrut areas, as
      well as autofluorescent ceroids. Moreover, in response to neoatherosclerosis,
      tertiary lymphoid organs (tissue lymphoid clusters) often developed in the
      adventitia. Some of these features could be reproduced in an experimental carotid
      stenting model in rabbits fed a high-cholesterol diet. Foam cells were present in
      all samples, and peristrut red blood cells (RBCs) were also detected, as shown by
      iron deposits and Bandeiraea simplicifiola isolectin-B4 staining of RBC
      membranes. Finally, in silico models were used to evaluate the compliance
      mismatch between the rigid struts and the distensible arterial wall using finite
      element analysis. They show that stenting approximately doubles the local von
      Mises stress in the intimal layer. CONCLUSIONS: We show here that stent
      implantation both in human and in rabbit arteries is characterized by local
      peristrut microhemorrhages and finally by both cholesterol accumulation and
      oxidation, triggering together in-stent neoatherosclerosis. Our data indicate
      that these processes are likely initiated by an increased mechanical stress due
      to the compliance mismatch between the rigid stent and the soft wall.

PMID- 27865169
TI  - The effect of TiO2 nanoparticles removal on drinking water quality produced by
      conventional treatment C/F/S.
AB  - Nanoparticles, namely titanium dioxide (TiO2), are emerging contaminants widely
      used to commercial and industrial applications, are a potential hazard and can
      cause damage to environment and human health due to their toxicity. Therefore,
      their removal from the water is urgent to minimize or eliminate the adverse
      environmental and human effects. This work, investigates the efficiency of
      conventional coagulation/flocculation/sedimentation (C/F/S) from drinking water
      treatment to remove TiO2 nanoparticles (NPs) from surface waters, and pretends to
      understand if the removal of TiO2 NPs affects the ability of C/F/S to remove
      natural organic matter (NOM) and turbidity, and consequently affects the quality
      of the treated water. Results show that TiO2 NPs removal is high (>90%) for all
      the waters studied (hydrophobic and hydrophilic waters) and the treated water
      quality is not compromised (turbidity, Ti and Al concentrations, pH and
      conductivity are below the national and international guidelines). In addition,
      TiO2 initial concentrations, ranging between 0.2 and 10 mg/L, have not a
      significant impact on NPs removal by C/F/S. Therefore, the widely used
      polyaluminium based coagulants are effective in the removal of TiO2 NPs by
      conventional C/F/S treatment, but removal is strongly influenced by the water
      characteristics. Hydrophobic waters need a higher coagulant dose than hydrophilic
      waters to achieve the same TiO2 NPs removals, as well as water with higher
      UV254nm values. The principal mechanism involved in TiO2 NPs removal is charge
      neutralisation.

PMID- 27865170
TI  - Long-term wastewater irrigation of vegetables in real agricultural systems:
      Concentration of pharmaceuticals in soil, uptake and bioaccumulation in tomato
      fruits and human health risk assessment.
AB  - Wastewater (WW) reuse for vegetable crops irrigation is regularly applied
      worldwide. Such a practice has been found to allow the uptake of pharmaceutical
      active compounds (PhACs) by plants and their subsequent entrance to the food web,
      representing an important alternative pathway for the exposure of humans to
      PhACs, with potential health implications. Herein we report the impacts of the
      long-term (three consecutive years) WW irrigation of a tomato crop with two
      differently treated effluents under real agricultural conditions, on (1) the soil
      concentration of selected PhACs (i.e. diclofenac, DCF; sulfamethoxazole, SMX;
      trimethoprim, TMP), (2) the bioaccumulation of these PhACs in tomato fruits, and
      (3) the human risks associated with the consumption of WW-irrigated fruits.
      Results revealed that the concentration of the studied PhACs in both the soil and
      tomato fruits varied depending on the qualitative characteristics of the treated
      effluent applied and the duration of WW irrigation. The PhAC with the highest
      soil concentration throughout the studied period was SMX (0.98 MUg kg-1),
      followed by TMP (0.62 MUg kg-1) and DCF (0.35 MUg kg-1). DCF was not found in
      tomato fruits harvested from WW-irrigated plants during the first year of the
      study. However, DCF displayed the highest fruit concentration (11.63 MUg kg-1)
      throughout the study (as a result of prolonged WW irrigation), followed by SMX
      (5.26 MUg kg-1) and TMP (3.40 MUg kg-1). The calculated fruit bioconcentration
      factors (BCFF) were extremely high for DCF in the 2nd (108) and 3rd year (132) of
      the experimental period, with the respective values for SMX (0.5-5.4) and TMP
      (0.2-6.4) being significantly lower. The estimated threshold of toxicity concern
      (TTC) and hazard quotients (HQ) values revealed that the consumption of fruits
      harvested from tomato plants irrigated for long period with the WW applied for
      irrigation under field conditions in this study represent a de minimis risk to
      human health. However, more studies need to be performed in order to obtain more
      solid information on the safety of WW reuse for irrigation.

PMID- 27865172
TI  - Settling regimen transitions quantify solid separation limitations through
      correlation with floc size and shape.
AB  - This study monitored three different activated sludge systems from the Blue
      Plains Advanced Wastewater Plant for a 1 year period to explore the relationship
      between effluent quality and activated sludge settling and flocculation behavior.
      Hindered settling rates (ISV) and sludge volume index (SVI) measurements were
      collected weekly. Novel metrics based on the solids concentration at which the
      transition between settling regimens occurred were also collected weekly. The
      transitional metrics were Threshold of Flocculation (TOF), and Limit of Stokesian
      Settling (LOSS). They marked the transition from discreet to flocculant settling,
      and from flocculant to hindered settling, respectively. A pilot clarifier and
      settling column were run and filmed to determine floc morphological properties.
      SVI was found to lose sensitivity (r < 0.20) when characterizing ISV above a
      hindered settling rate of 3 m h-1. ISV and LOSS had a strong correlation (r =
      0.71), but ISV was subject to change, depending on the solids concentration. Two
      sludge matrix limitations influencing effluent quality were characterized by
      transition concentrations; pinpoint floc formation, and loose floc formation.
      Pinpoint flocs had TOF values above 400 mg TSS L-1; loose floc formation sludge
      had TOF and LOSS values below 400 mg TSS L-1 and 900 mg TSS L-1, respectively.
      TOF was found to correlate with the particle size distribution while LOSS
      correlated to the settling velocity distribution. The use of both TOF and LOSS is
      a quick and effective way to characterize limitations effecting effluent quality.

PMID- 27865171
TI  - Iron and manganese removal: Recent advances in modelling treatment efficiency by
      rapid sand filtration.
AB  - A model has been developed that takes into account the main characteristics of
      (submerged) rapid filtration: the water quality parameters of the influent water,
      notably pH, iron(II) and manganese(II) concentrations, homogeneous oxidation in
      the supernatant layer, surface sorption and heterogeneous oxidation kinetics in
      the filter, and filter media adsorption characteristics. Simplifying assumptions
      are made to enable validation in practice, while maintaining the main mechanisms
      involved in iron(II) and manganese(II) removal. Adsorption isotherm data
      collected from different Dutch treatment sites show that Fe(II)/Mn(II) adsorption
      may vary substantially between them, but generally increases with higher pH. The
      model is sensitive to (experimentally) determined adsorption parameters and the
      heterogeneous oxidation rate. Model results coincide with experimental values
      when the heterogeneous rate constants are calibrated.

PMID- 27865173
TI  - Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.
AB  - OBJECTIVE: Cognitive impairment is frequently observed in patients with temporal
      lobe epilepsy. It is hypothesized that cumulative seizure exposure causes
      accelerated cognitive decline in patients with epilepsy. We investigated the
      influence of seizure frequency on cognitive decline in a rodent model for
      temporal lobe epilepsy. METHODS: Neurobehavioral assessment was performed before
      and after surgery, after the induction of self-sustaining limbic status
      epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent
      seizures. Furthermore, we assessed potential confounders of memory performance.
      RESULTS: Rats showed a deficit in spatial working memory after the induction of
      the SSLSE, which endured in the chronic phase. A progressive decline in
      recognition memory developed in SSLSE rats. Confounding factors were absent.
      Seizure frequency and also the severity of the status epilepticus were not
      correlated with the severity of cognitive deficits. SIGNIFICANCE: The effect of
      the seizure frequency on cognitive comorbidity in epilepsy has long been debated,
      possibly because of confounders such as antiepileptic medication and the
      heterogeneity of epileptic etiologies. In an animal model of temporal lobe
      epilepsy, we showed that a decrease in spatial working memory does not relate to
      the seizure frequency. This suggests for other mechanisms are responsible for
      memory decline and potentially a common pathophysiology of cognitive
      deterioration and the occurrence and development of epileptic seizures.
      Identifying this common denominator will allow development of more targeted
      interventions treating cognitive decline in patients with epilepsy. The treatment
      of interictal symptoms will increase the quality of life of many patients with
      epilepsy.

PMID- 27865174
TI  - Maraviroc in addition to cART during primary HIV infection: Results from MAIN
      randomized clinical trial and 96-weeks follow-up.
AB  - BACKGROUND: Multi-targeted treatment strategies including maraviroc (MVC) during
      Primary HIV Infection (PHI) may benefit from the immune-modulatory properties of
      this CCR5-inhibitor. OBJECTIVES: We conducted a proof-of-concept clinical trial
      aimed at assessing whether maraviroc in addition of a combination antiretroviral
      therapy (cART) initiated during PHI would improve immunological and virological
      parameters. STUDY DESIGN: The MAIN (Maraviroc in HIV Acute INfection) study was a
      randomized open-label clinical trial (EUDRACT number: 2008-007004-29) which
      enrolled 29 patients with PHI. Subjects were randomly assigned to receive cART
      only (cART), cART+8 weeks of MVC (ST-MVC) or cART+48 weeks of MVC (LT-MVC),
      regardless of predicted co-receptor usage. After 48 weeks patients in ST-MVC and
      LT-MVC groups discontinued MVC. Patients were evaluated at week 48 and at week 96
      of follow-up to assess differences in CD4 T-cell gain and plasma HIV-RNA.
      RESULTS: Twenty-nine patients were enrolled. Seven patients (24%) had a predicted
      CXCR4 co-receptor usage. At week 48, 27 patients (93.1%) reached HIV
      RNA<50cps/mL. Median CD4 T-cell count increase was 313 cells/MUL (p<0.001,
      Wilcoxon signed-rank test). At multivariate linear regression analysis, LT-MVC
      arm had the greatest CD4 T-cell increase, while patients in ST-MVC arm had the
      least gain in CD4 T-cells (p=0.007). At week 96, multivariate analysis showed no
      associations between former treatment arm and CD4 T-cell gain. CONCLUSIONS: The
      MAIN study showed that MVC for 48 weeks in addition to cART during PHI was able
      to enhance CD4 T-cell gain, regardless of co-receptor usage. After MVC
      discontinuation, the difference between treatment arms was lost.

PMID- 27865176
TI  - Adoptive immunotherapy for hematological malignancies: Current status and new
      insights in chimeric antigen receptor T cells.
AB  - Hematological malignancies frequently express cancer-associated antigens that are
      shared with normal cells. Such tumor cells elude the host immune system because
      several T cells targeted against self-antigens are removed during thymic
      development, and those that persist are eliminated by a regulatory population of
      T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a
      novel modality for tumor immunotherapy due to their powerful efficacy against
      tumor cells. These cells are created by transducing genes-coding fusion proteins
      of tumor antigen-recognition single-chain Fv connected to the intracellular
      signaling domains of T cell receptors, and are classed as first-, second- and
      third-generation, differing on the intracellular signaling domain number of T
      cell receptors. CAR-T treatment has emerged as a promising approach for patients
      with hematological malignancies, and there are several works reporting clinical
      trials of the use of CAR-modified T-cells in acute lymphoblastic leukemia,
      chronic lymphoblastic leukemia, multiple myeloma, lymphoma, and in acute myeloid
      leukemia by targeting different antigens. This review reports the history of
      adoptive immunotherapy using CAR-Ts, the CAR-T manufacturing process, and T cell
      therapies in development for hematological malignancies.

PMID- 27865175
TI  - JAK2V617F-mutant vascular niche contributes to JAK2V617F clonal expansion in
      myeloproliferative neoplasms.
AB  - The myeloproliferative neoplasms (MPNs) are characterized by hematopoietic
      stem/progenitor cell (HSPC) expansion and overproduction of blood cells. The
      acquired mutation JAK2V617F plays a central role in these disorders. Mechanisms
      responsible for MPN HSPC expansion is not fully understood, limiting the
      effectiveness of current treatments. Endothelial cells (ECs) carrying the
      JAK2V617F mutation can be detected in patients with MPNs, suggesting that ECs are
      involved in the pathogenesis of MPNs. Here we report that JAK2V617F-bearing
      primary murine ECs have increased cell proliferation and angiogenesis in vitro
      compared to JAK2WT ECs. While there was no difference between JAK2V617F and
      JAK2WT HSPC proliferation when co-cultured with JAK2WT EC, the JAK2V617F HSPC
      displayed a relative growth advantage over the JAK2WT HSPC when co-cultured on
      JAK2V617F EC. In addition, the thrombopoietin (TPO) receptor MPL is up regulated
      in JAK2V617F ECs and contributes to the maintenance/expansion of the JAK2V617F
      clone over JAK2WT clone in vitro. Considering that ECs are an essential component
      of the hematopoietic niche and most HSPCs reside in the perivascular niche, our
      studies suggest that the JAK2V617F-bearing ECs form an important component of the
      MPN vascular niche and contribute to mutant stem/progenitor cell expansion,
      likely through a critical role of the TPO/MPL signaling axis.

PMID- 27865177
TI  - Association of plasma xanthine oxidoreductase activity with severity and clinical
      outcome in patients with chronic heart failure.
AB  - BACKGROUND: Oxidative stress due to purine degradation is associated with the
      development of chronic heart failure (CHF). Xanthine oxidoreductase (XOR) is a
      rate-limiting enzyme of purine degradation that plays a key role in uric acid
      (UA) production with a resultant increase in reactive oxygen species. However,
      the relationship between plasma XOR activity and CHF severity and clinical
      outcome remains unclear. METHODS AND RESULTS: We measured XOR activity in 440
      patients with CHF and 44 control subjects. Abnormally high and low XOR activities
      were identified based on the results for 95% of the control subjects (high and
      low XOR activities >=120 and <33pmol/100MUL/h, respectively). The prevalence
      rates of high and low XOR activities increased with advancing New York Heart
      Association functional class. There were 158 cardiac events during a median
      follow-up period of 1034days. Multivariate Cox proportional hazard regression
      analysis showed that both high and low XOR activities were significantly
      associated with cardiac events in patients with CHF after adjustment for
      confounding risk factors including serum UA and loop diuretic use. Kaplan-Meier
      analysis revealed that the cardiac event rate was significantly higher in
      patients with either high or low XOR activity. The net reclassification index was
      significantly improved by adding XOR activity to the basic risk factors.
      CONCLUSIONS: We provide the first evidence of an association of plasma XOR
      activity with CHF severity and clinical outcome. Plasma XOR activity could be
      used to identify high-risk CHF patients and could be a therapeutic target for XOR
      inhibitors.

PMID- 27865178
TI  - Usefulness of soluble urokinase plasminogen activator receptor (suPAR) as an
      inflammatory biomarker in obese children.
AB  - OBJECTIVE: Soluble urokinase plasminogen activator receptor (suPAR) has emerged
      as a relatively new biomarker that reflects increased inflammatory status and
      been associated with cardiovascular risk. We wanted to investigate the predictive
      value and usefulness of suPAR as an inflammatory biomarker in obese children.
      METHODS AND RESULTS: Of the total 136 participants, 76 (36 male, 40 female) were
      in obese group and 60 (24 male, 36 female) were in control group. The median age
      was 12.05 (6.16-17.30) years old for obese group, and 12.83 (8.00-16.75) years
      old for control group. Obese children had statistically significantly higher
      heart rate, systolic and diastolic blood pressure, EAT and LV mass than control
      group (p<0.01). The median suPAR level in obese group was not statistically
      different than in control group (0.54 vs. 0.59, p=0.26). The median hsCRP level
      in obese group was found statistically significantly higher than in control group
      (1.97 vs. 0.41, p<0.01). A significant positive correlation between hsCRP and BMI
      in the obese participants was found (r=0.45, p<0.01), but not a relationship
      between suPAR and BMI (r=-0.21, p>0.05). CONCLUSION: Our research did not
      demonstrate the usefulness of suPAR as an inflammatory biomarker and a predictive
      value for future atherosclerosis in obese children. Further studies with larger
      sample size are required to determine whether suPAR is useful as an inflammatory
      biomarker in childhood obesity.

PMID- 27865179
TI  - Right coronary artery disappeared after giant right coronary artery fistula
      draining into left ventricle occluded by VSD occluder-What we can learn from
      this?

PMID- 27865180
TI  - Detection of right ventricular myocardial fibrosis using quantitative CT
      attenuation of the right ventricular myocardium in the late phase on 320 slice CT
      in subjects with pulmonary hypertension.
AB  - PURPOSE: Right ventricular myocardial (RVM) fibrosis may be a significant
      indicator of prognosis in pulmonary hypertension (PH). To detect the presence of
      RVM fibrosis in PH subjects, we employed ECG gated 320-slice CT. METHODS: 62
      confirmed PH subjects (16 males; 55+/-16years; 45 chronic thromboembolic PH
      (CTEPH) who underwent conventional non-surgical medical therapy; and 17 pulmonary
      arterial hypertension (PAH)) underwent ECG-gated 320-slice CT. On CT, RV fibrosis
      was defined as contrast defect in the early phase and conversely abnormal
      enhancement in the late phase. RESULTS: RVM fibrosis was observed in 14 subjects
      (23%) on CT (CTEPH 22%; PAH 29%; P=0.91). CT attenuation of RVM in the late phase
      was significantly greater in subjects with RVM fibrosis than in those without
      (P=0.025). ROC curves of CT attenuation of RVM in the early and late phase, and
      ratio of CT attenuation of RVM in the early phase/late phase showed AUCs of 0.55,
      0.70, and 0.65, respectively. The best cutoff points of 79.5 HU (sensitivity of
      50% and specificity of 69% for CT attenuation of RVM in the early phase, P=0.59),
      99.5 HU (sensitivity of 50% and specificity of 88% for CT attenuation of RVM in
      the late phase, P=0.025), and 1.416 (sensitivity of 29% and specificity of 94%
      for ratio of CT attenuation of RVM in the early phase/late phase, P=0.092) were
      used to distinguish subjects+/-RVM fibrosis. CONCLUSION: Quantitative-measurement
      of CT attenuation of RVM in the late phase may be able to detect presence of RVM
      fibrosis in PH subjects.

PMID- 27865181
TI  - Radial artery diameter does not correlate with body mass index: A duplex
      ultrasound analysis of 1706 patients undergoing trans-radial catheterization at
      three experienced radial centers.
AB  - BACKGROUND: We examined whether the radial artery diameter is correlated with
      body mass index (BMI) in patients undergoing transradial catheterization.
      METHODS: 1706 patients undergoing trans-radial catheterization at three
      experienced, high-volume, radial centers were analyzed. Radial and ulnar artery
      diameters were determined by ultrasound in the distal third of the forearm one
      day post procedure. Pearson correlation test was used to measure the relationship
      between continuous variables. RESULTS: Radial diameter was larger than the ulnar
      artery [median 2.8mm (interquartile range (IQR): 2.4-3.1mm) vs. median 2.4mm
      (IQR: 2.1-2.6mm), p<0.001]. Women had smaller radial and ulnar arteries compared
      to men [median 2.6mm (IQR: 2.3-2.9mm) vs. median 2.8 (IQR: 2.4-3.2mm), p<0.001
      and median 2.2mm (IQR: 2.0-2.5mm) vs. median 2.5mm (IQR: 2.2-2.7mm), p<0.001,
      respectively]. There was no correlation between radial diameter and BMI (Pearson
      correlation=0.003, p=0.88 (2-sided)), but a strong linear correlation between the
      radial and ulnar artery diameter existed (Pearson correlation=0.48, p<0.001 (2
      sided)). After adjustment for clinical variables including diabetes, gender, and
      age, female gender was associated with smaller radial diameter (<2.8mm) (odds
      ratio 1.72; 95% CI 1.40-2.12, p<0.001). CONCLUSIONS: No correlation was observed
      between radial artery diameter and BMI, although female gender was associated
      with smaller radial diameter. This suggests catheterization can be performed
      without anthropometric consideration, although it should be recognized women may
      have smaller radial arteries. As the diameter of the radial is larger than the
      ulnar artery, the radial should remain the default catheterization access-site.

PMID- 27865182
TI  - Early initiation of eicosapentaenoic acid and statin treatment is associated with
      better clinical outcomes than statin alone in patients with acute coronary
      syndromes: 1-year outcomes of a randomized controlled study.
AB  - BACKGROUND: Early initiation of EPA treatment in combination with a statin within
      24h after percutaneous coronary intervention (PCI) in patients with acute
      myocardial infarction (MI) reduces inflammation and ventricular arrhythmia
      compared with statin monotherapy; however, the impact of early initiation of EPA
      treatment on cardiovascular events is unclear. We determined whether early
      eicosapentaenoic acid (EPA) treatment in patients with acute coronary syndrome
      (ACS) reduces adverse cardiovascular events. METHODS: This prospective, open
      label, blind end point-randomized trial consisted of 241 patients with ACS.
      Patients were randomly assigned to receive pitavastatin (2mg/day) with or without
      1800mg/day of EPA initiated within 24h after PCI. The primary endpoint was
      defined as cardiovascular events occurring within 1year, including death from a
      cardiovascular cause, nonfatal stroke, nonfatal MI and revascularization.
      RESULTS: The mean EPA/arachidonic acid ratio at follow-up was 0.40 in the control
      group and 1.15 in the EPA group. A primary endpoint event occurred in 11 patients
      (9.2%) in the EPA group and 24 patients (20.2%) in the control group (absolute
      risk reduction, 11.0%; hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.87;
      P=0.02). Notably, death from a cardiovascular cause at 1year was significantly
      lower in the EPA group than in the control group (0.8% vs. 4.2%, P=0.04).
      CONCLUSIONS: Early initiation of treatment with EPA combined with statin after
      successful primary PCI reduced cardiovascular events after ACS. CLINICAL TRIAL
      REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR); Registry Number,
      UMIN000016723; URL, http://www.umin.ac.jp/ctr/index-j.htm.

PMID- 27865183
TI  - Feasibility of low radiation dose retrospectively-gated cardiac CT for functional
      analysis in adult congenital heart disease.
AB  - BACKGROUND: The use of cardiac computed tomography (CT) in the evaluation of
      adult congenital heart disease patients is limited due to concerns of high
      radiation doses. The purpose of this study was to prospectively assess whether
      low radiation dose cardiac CT is feasible to evaluate ventricular systolic
      function in adults with congenital heart disease. METHODS: The study group
      included 30 consecutive patients with significant congenital heart disease who
      underwent a total of 35 ECG-gated cardiac CT scans utilizing a 320-detector row
      CT scanner. Each study included a non-contrast scan and subsequent contrast
      enhanced retrospectively-gated acquisition. Effective radiation dose was
      estimated by multiplying the dose length product by a k-factor of 0.014mSv/mGycm.
      RESULTS: The mean age of the patients was 34.4+/-8.9years, 60% were men, and mean
      body mass index was 24.2+/-4.3kg/m2. A majority of patients (n=28, 93.3%) had
      contraindications to cardiac MRI. A tube potential of 80kV was used in 27 (77.1%)
      of the contrast-enhanced scans. The mean signal-to-noise and contrast-to-noise
      ratios were 11.5+/-3.9 and 10.3+/-3.7, respectively. The median radiation dose
      for non-contrast and contrast-enhanced images were 0.1mSv (0.07-0.2mSv) and
      0.94mSv (0.5-2.1mSv), respectively. All 35 CT scans were successfully analyzed
      for ventricular systolic function. CONCLUSIONS: A low radiation contrast
      enhanced, retrospectively-gated cardiac CT with a median radiation dose of less
      than 1mSv was successful in evaluating ventricular systolic function in 30
      consecutive adult congenital heart disease patients who underwent a total of 35
      scans.

PMID- 27865184
TI  - Changes of left ventricular mechanics after trans-catheter aortic valve
      implantation and surgical aortic valve replacement for severe aortic stenosis: A
      tissue-tracking cardiac magnetic resonance study.
AB  - BACKGROUND: Left ventricular (LV) mechanics are impaired in patients with severe
      aortic stenosis (AS). The aim of the present study was to assess their changes
      early and late after trans-catheter aortic valve implantation (TAVI) and surgical
      aortic valve replacement (AVR) using cardiac magnetic resonance (CMR) tissue
      tracking imaging. METHODS: In 59 patients with severe AS undergoing either TAVI
      (n=35) or surgical AVR (n=24), CMR with late gadolinium enhancement (LGE) imaging
      was performed before and early post-procedure to evaluate LV function and mass,
      and presence/extent of LGE. A third CMR scan was performed in 29 patients after a
      mean follow-up of 15+/-4months. Tissue-tracking analysis was applied to cine CMR
      images, to assess LV global longitudinal (GLS), circumferential (GCS) and radial
      (GRS) strains. RESULTS: The TAVI and surgical AVR groups were similar with
      respect to baseline (p=0.14) and early post-procedure (p=0.16) LV ejection
      fraction. However, baseline LV GLS was significantly impaired in TAVI patients
      compared to surgical AVR patients (p=0.025). Early post-procedure, TAVI resulted
      in a significant improvement of LV GLS (p=0.003), while a significant worsening
      of LV GLS was observed early after surgical AVR (p=0.012). At longer term follow
      up, both TAVI and surgical AVR groups experienced a significant reduction of LV
      mass and a significant improvement of LV myocardial mechanics in all the three
      directions. CONCLUSIONS: Treatment-specific differences in the changes of LV
      myocardial mechanics early after afterload release by TAVI and surgical AVR are
      present. Later, both interventions are associated with an improvement of LV
      myocardial deformation, alongside a regression of LV hypertrophy.

PMID- 27865185
TI  - A new era in the management of type 2 diabetes: Is cardioprotection at long last
      a reality?
AB  - The EMPA-REG OUTCOME and the LEADER trials have revealed a new era in the
      management of type 2 diabetes. The SGLT2 inhibitor empagliflozin demonstrated a
      lower rate of the primary composite outcome of death from cardiovascular causes,
      nonfatal myocardial infarction, or nonfatal stroke compared to placebo.
      Liraglutide, a GLP-1 analogue, succeeded to demonstrate reduction on a composite
      outcome including first occurrence of cardiovascular death, nonfatal myocardial
      infarction or non-fatal stroke. These two medications act through different
      mechanisms and has consequently shown different patterns of cardiovascular
      benefit. In one hand, empagliflozin showed an earlier effect compared to those
      observed using liraglutide. On the other hand, the difference between
      empagliflozin and placebo was driven by a significant reduction in death from
      cardiovascular causes, with and striking disconnect showing no significant
      between-group difference in the risk of myocardial infarction or stroke. In
      contrast, liraglutide reduced consistently all components of the composite
      endpoint. Based on the different temporal pattern of achieving clinical benefit
      one might flirt with the idea that liraglutide seems to provide a chronic
      "protection" that better fits in a longer metabolic effect with an impact in the
      progression of atherosclerosis, whilst empagliflozin provides an acute effect
      compatible with an immediate hemodynamic action. After years going from "bench to
      bedside" in order to discover the holy grail of cardioprotection, these 2 new
      studies suggest that we may have reached this state and it is time to go from
      "bed back to bench side" to understand the mechanisms of this potential paradigm
      shift.

PMID- 27865186
TI  - Relationship between neutrophil-lymphocyte ratio and severity of lower extremity
      peripheral artery disease.
AB  - BACKGROUND: The aim of this study was to determine the association between
      neutrophil-lymphocyte ratio (NLR) and severity of lower extremity peripheral
      artery disease (PAD). METHODS: A retrospective chart review identified 928
      patients referred for peripheral angiography. NLR was assessed from routine pre
      procedural hemograms with automated differentials and available in 733 patients.
      Outcomes of interest were extent of disease on peripheral angiography and target
      vessel revascularization. Median follow-up was 10.4months. Odds ratio (OR) [95%
      confidence intervals] was assessed using a logistic regression model. RESULTS:
      There was a significant association between elevated NLR and presence of severe
      multi-level PAD versus isolated suprapopliteal or isolated infrapopliteal disease
      (OR 1.11 [1.03-1.19], p=0.007). This association remained significant even after
      adjustment for age (OR 1.09 [1.01-1.17], p=0.02); age, sex, race, and body mass
      index (OR 1.08 [1.00-1.16], p=0.046); and age, sex, race, body mass index,
      hypertension, diabetes mellitus, coronary artery disease, and creatinine (OR 1.07
      [1.00-1.15], p=0.049). After additional adjustment for clinical presentation,
      there was a trend towards association between NLR and severe multi-level PAD (OR
      1.07 [1.00-1.15], p=0.056), likely limited by sample size. In patients who
      underwent endovascular intervention (n=523), there was no significant difference
      in rate of target vessel revascularization across tertiles of NLR (1st tertile
      14.8%, 2nd tertile 14.1%, 3rd tertile 20.1%; p=0.32). CONCLUSION: In a
      contemporary cohort of patients undergoing peripheral angiography with possible
      endovascular intervention, elevated NLR was independently associated with severe
      multi-level PAD. Larger studies evaluating the association between this
      inexpensive biomarker and clinical outcomes are warranted.

PMID- 27865187
TI  - Final shape of biovascular scaffolds and clinical outcome. Results from a
      multicenter all-comers study with intravascular imaging.
AB  - AIMS: Radial strength of bioresorbable vascular scaffolds (BVS) implanted in
      coronary arteries is still under debate. Moreover, their final shape patterns,
      when implanted in an all-comer, unselected population, have not yet been
      completely correlated with clinical outcome and should be better investigated.
      METHODS AND RESULTS: A multicenter collaborative analysis was performed on all
      consecutive patients with native coronary artery disease undergoing PCI with
      intravascular imaging-guided BVS implantation. The BVS was arbitrarily
      categorized as having a final "oval shape" through intravascular imaging, if
      maximal lumen diameter was longer than 150% of minimal lumen diameter at the
      target lesion. Primary study-endpoint was device-oriented major adverse events
      (DOCE) at mid-term follow-up. Sixty-seven consecutive patients were evaluated at
      6 European centers. Mean patient age was 58+/-11years, and 12 patients (18%) had
      diabetes. Mean percent diameter stenosis was 79+/-12.5%. Average lesion length
      was 24.4+/-13.8mm and 66% of lesions were AHA/ACC type B2/C. Postdilation rate
      was 91% and all BVS resulted well apposed to the vessel wall. Procedural success
      was achieved in all patients and 10 (14.9%) had an "oval shape" at intravascular
      imaging. This occurrence was not associated with an increase in periprocedural
      myocardial infarction (p=0.37) or DOCE during hospitalization (p=0.65). Seven
      month DOCE occurred in 3 patients (5.6%) of the oval shape group, they were
      target-vessel revascularization and did not differ significantly between patients
      with vs. without final "oval shape" (p=0.34). We did not register episodes of
      scaffold thromboses. CONCLUSIONS: In an all-comer population with complex
      coronary lesions treated with BVS, a final oval shape after postdilation was not
      rare and not associated with immediate and medium term adverse events.

PMID- 27865188
TI  - The impact of digoxin on mortality in patients with chronic systolic heart
      failure: A propensity-matched cohort study.
AB  - BACKGROUND: Prior Studies showed mixed results in association of digoxin use with
      all-cause mortality (ACM). The aim of this analysis is to identify the impact of
      digoxin use on ACM in a contemporary heart failure (HF) cohort treated with
      guideline based therapy. METHODS: We included 2298 consecutive patients seen in
      an HF clinic between 2000 and 2015. Patients were considered to be a digoxin user
      if he/she received digoxin at any point during the enrollment period in the HF
      clinic. Patients were matched based on digoxin utility using propensity matching
      in 2-3:1 fashion. The primary outcome was ACM. RESULT: Of 2298 patients, 325
      digoxin users were matched with 750 non-digoxin users. The Matched cohort did not
      have differences among demographics and clinical variables except for worse HF
      symptomatology and increased prevalence of atrial fibrillation. Overall, the
      prevalence of the use of guideline suggested therapies was 96%. After a median
      follow-up duration of 4years (IQR 2-6years), digoxin use was associated with
      increased ACM (21.8% versus 12.9%, unadjusted HR=1.81; 95% CI=1.33 to 2.45;
      p=0.001). This association remained significant after adjusting for the
      propensity score, atrial fibrillation, ejection fraction, and New York HF Class
      (HR=1.74; 95% CI=1.20 to 2.38; p<0.0001). CONCLUSION: In this analysis of well
      treated HF patients, digoxin was associated with increased ACM. Further
      randomized controlled trials are needed to determine whether digoxin therapy
      should be used in well-treated HF patients. Until then, routine use of digoxin in
      clinical practice should be discouraged.

PMID- 27865189
TI  - Screening entire healthcare system ECG database: Association of deep terminal
      negativity of P wave in lead V1 and ECG referral with mortality.
AB  - BACKGROUND: Each encounter of asymptomatic individuals with the healthcare system
      presents an opportunity for improvement of cardiovascular disease (CVD) awareness
      and sudden cardiac death (SCD) risk assessment. ECG sign deep terminal negativity
      of the P wave in V1 (DTNPV1) was shown to be associated with an increased risk of
      SCD in the general population. OBJECTIVE: To evaluate association of DTNPV1 with
      all-cause mortality and newly diagnosed atrial fibrillation (AFib) in the large
      tertiary healthcare system patient population. METHODS: Retrospective double
      cohort study compared two levels of exposure (automatically measured amplitude of
      P-prime (Pp) in V1): DTNPV1 (Pp from -100MUV to -200MUV) and ZeroPpV1 (Pp=0). An
      entire healthcare system (2010-2014) ECG database was screened. Medical records
      of children and patients with previously diagnosed AFib/atrial flutter (AFl),
      implanted pacemaker or cardioverter-defibrillator were excluded. DTNPV1 (n=3,413)
      and ZeroPpV1 (n=3,405) cohorts were matched by age and sex. Primary outcome was
      all-cause mortality. Secondary outcomes were newly diagnosed AFib/AFl. Median
      follow-up was 2.5 y. RESULTS: DTNPV1 was associated with all-cause mortality (HR
      1.95(1.64-2.31); P<0.0001) and newly diagnosed AFib (HR 1.29(1.04-1.59); P=0.021)
      after adjustment for CVD, comorbidities, other ECG parameters, medications, and
      index ECG referral. Index ECG referral by a cardiologist was independently
      associated with 34% relative risk reduction of mortality (HR 0.66(0.52-0.84);
      P=0.001), as compared to ECG referral by a non-cardiologist. CONCLUSION: DTNPV1
      is independently associated with twice higher risk of all-cause death, as
      compared to patients without P prime in V1. Life-saving effect of the index ECG
      referral by a cardiologist requires further study.

PMID- 27865190
TI  - Effect of potassium supplementation on vascular function: A meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Effects of potassium supplementation on vascular function remain
      conflicting. This meta-analysis aimed to summarized current literature to fill
      the gaps in knowledge. METHODS: A literature search was performed on PubMed
      database through April, 2016. The measurements of vascular function included
      pulse wave velocity (PWV), augmentation index (AI), pulse pressure (PP), flow
      mediated dilatation (FMD), glycerol trinitrate responses (GTN), and intercellular
      cell adhesion molecule-1 (ICAM-1). Data were pooled as standardized mean
      difference (SMD) with 95% confidence intervals. RESULTS: Seven randomized
      controlled trials examining 409 participants were included, with dosage of
      potassium ranging from 40 to 150mmol/day, and duration of intervention from 6days
      to 12months. Pooling results revealed a significant improvement in PP (SMD 
      0.280, 95% CI -0.493 to -0.067, p=0.010), but no improvement in PWV (SMD -0.342,
      95% CI -1.123 to 0.440, p=0.391), AI (SMD -0.114, 95% CI -0.282 to 0.054,
      p=0.184), FMD (SMD 0.278, 95% CI -0.321 to 0.877, p=0.363), GTN (SMD -0.009, 95%
      CI -0.949 to 0.930, p=0.984), and ICAM-1 (SMD -0.238, 95% CI -0.720 to 0.244,
      p=0.333). CONCLUSIONS: Potassium supplementation was associated with significant
      improvement of PP, rather than other measurements of vascular function. However,
      the small number of researches and wide variation of evidences make it difficult
      to make a definitive conclusion.

PMID- 27865191
TI  - Inverse association between type 2 diabetes and aortic root dimension in
      hypertensive patients.
AB  - BACKGROUND: Some data support the concept that aortic root diameter (ARD) in
      hypertension may be regarded as a marker of subclinical organ damage. The impact
      of type 2 diabetes mellitus (DM) on cardiac structure and function is known,
      although the relationship between DM and ARD is not clear. The aim of our study
      was to evaluate the influence of DM on ARD in hypertensive patients. METHODS: We
      enrolled 1693 hypertensive patients (aged 63.7+/-9.6years). The population was
      divided into two groups: the first one with DM (n=747) and the second one without
      DM (n=946). ARD was measured by echocardiography at level of Valsalva's sinuses
      using echocardiography M-mode tracings. It was considered as absolute measure and
      normalized to height (ARD/H) and body surface area (ARD/BSA). Left ventricular
      mass index (LVMI) and some parameters of systolic and diastolic function have
      been valued by means of echocardiography and tissue Doppler imaging. RESULTS: The
      DM group was characterized by more elevated values of LVMI and a worst systolic
      and diastolic function. ARD value was significantly lower in DM group in
      comparison to patients without DM only when indexed for BSA (ARD/BSA=18.7+/
      2.3mm/m2 vs 18.3+/-2.0mm/m2, p=0.01). This difference remained statistically
      significant, even after correction by age, sex and BMI (p=0.01). A multivariate
      linear regression analysis demonstrated an inverse relationship between DM and
      ARD/BSA after correction for potential confounders (beta=0.10, p<0.001).
      CONCLUSIONS: Our results confirm the hypothesis of a protective role of DM on
      aortic root dilatation.

PMID- 27865192
TI  - Effect of targeted therapy on circulating progenitor cells in precapillary
      pulmonary hypertension.
AB  - BACKGROUND: Endothelial dysfunction is key in the development of pulmonary
      hypertension (PH) and is associated with reduced number of circulating progenitor
      cells. Studies to date evaluating levels of circulating progenitor cells in PH
      have provided conflicting results. Current treatment of pulmonary arterial
      hypertension (PAH) and medical treatment of chronic thromboembolic pulmonary
      hypertension (CTEPH) targets endothelium dependent signalling pathways. The
      effect of PAH-targeted therapy on circulating progenitor cells has not been
      clearly established. OBJECTIVES: To investigate whether levels of circulating
      progenitor cells in treatment-naive patients with PAH or CTEPH differ from
      healthy subjects and to assess the effect of PAH-targeted therapy on the
      circulating levels of these progenitors. METHODS: Thirty controls, 33 PAH and 11
      CTEPH treatment-naive patients were studied. Eighteen patients with PAH and 9
      with CTEPH were re-evaluated 6-12months after starting PAH-targeted therapy.
      Levels of progenitors were measured by flow cytometry as CD45+CD34+ and
      CD45+CD34+CD133+ cells. RESULTS: Compared with controls, the number of
      circulating progenitor cells was reduced in PAH but not in CTEPH. After 6
      12months of treatment, levels of circulating progenitors increased in PAH and
      remained unchanged in CTEPH. Patients with lower exercise tolerance presented
      lower levels of circulating progenitors. No other relation was found between
      levels of progenitors and clinical or hemodynamic parameters. CONCLUSIONS:
      Patients with PAH, but not those with CTEPH, present reduced levels of
      circulating progenitor cells. PAH-targeted therapy increases levels of
      progenitors in PAH but not in CTEPH, suggesting different involvement of
      progenitor cells in the pathobiology of these pulmonary hypertensive disorders.

PMID- 27865194
TI  - High-sensitivity cardiac troponin T levels in the emergency department in
      patients with chest pain but no myocardial infarction.
AB  - BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced
      into clinical practice. The increased sensitivity has decreased the specificity.
      We aimed to determine the predictors for and prevalence of hs-cTnT levels above
      the 99th percentile in a stable population of patients without myocardial
      infarction (MI) who sought medical attention for chest pain in the emergency
      department. METHODS: We included 11,847 patients with chest pain and at least one
      hs-cTnT measurement during 2011 and 2012. Patients with any acute reasons for an
      elevated hs-cTnT level were excluded. We used logistic regression to calculate
      adjusted odds ratios with 95% confidence intervals for the association between
      patient characteristics and hs-cTnT levels of >14ng/L. We also determined 50th,
      75th, 97.5th, and 99th percentile values of hs-cTnT levels in relation to age,
      sex, estimated glomerular filtration rate (eGFR), and presence or absence of
      comorbidities. RESULTS: In total, 1360 (11%) patients had hs-cTnT levels of
      >14ng/L. Men had higher troponin levels than women, and older patients had higher
      levels than younger patients. The strongest predictor of an elevated troponin
      level was a reduced eGFR. The 99th percentile for hs-cTnT among all men and among
      women <50years of age with normal renal function was 20 and 12ng/L, respectively;
      this level increased to 44 and 36ng/L, respectively, at the age of 70-79years.
      CONCLUSIONS: A hs-cTnT level above the 99th percentile in patients with chest
      pain but no MI is common and is related to sex, age, and eGFR.

PMID- 27865193
TI  - Different clinical outcomes in patients with asymptomatic severe aortic stenosis
      according to the stage classification: Does the aortic valve area matter?
AB  - BACKGROUND: The ACC/AHA guidelines introduced a new classification of severe
      aortic stenosis (AS) mainly based on maximum jet velocity (Vmax) and mean
      pressure gradient (mPG), but not on aortic valve area (AVA). However, prognostic
      value of this new classification has not yet been fully evaluated. METHODS AND
      RESULTS: We studied 1512 patients with asymptomatic severe AS enrolled in the
      CURRENT AS registry in whom surgery was not initially planned. Patients were
      divided into 2 groups: Group 1 (N=122) comprised patients who met the
      recommendation for surgery; high-gradient (HG)-AS (Vmax>=4.0m/s or mPG>=40mmHg)
      with ejection fraction (EF)<50%, or very HG-AS (Vmax>=5.0m/s or mPG>=60mmHg), and
      Group 2 (N=1390) comprised patients who did not meet this recommendation. Group 2
      was further subdivided into HG-AS with preserved EF (HGpEF-AS, N=498) and low
      gradient (LG)-AS, but AVA<1.0cm2 (N=892). The excess risk of Group 1 relative to
      Group 2 for the primary outcome measure (a composite of aortic valve-related
      death or heart failure hospitalization) was significant (adjusted HR: 1.92,
      95%CI: 1.37-2.68, P<0.001). The excess risk of HGpEF-AS relative to LG-AS for the
      primary outcome measure was also significant (adjusted HR: 1.45, 95%CI: 1.11
      1.89, P=0.006). Among LG-AS patients, patients with reduced EF (<50%) (LGrEF-AS,
      N=103) had extremely high cumulative 5-year incidence of all-cause death (85.5%).
      CONCLUSION: Trans-aortic valve gradient in combination with EF was a good
      prognostic marker in patients with asymptomatic AS. However, patients with LGrEF
      AS had extremely poor prognosis when managed conservatively.

PMID- 27865195
TI  - A clinical model to identify patients with high-risk plaque by coronary computed
      tomography angiography.
AB  - OBJECTIVES: Current clinical models predict the pre-test probability of
      obstructive coronary artery disease, but these models do not predict the presence
      of high-risk plaques. Thus the objective of this study was to propose a model to
      predict high-risk plaque assessed by coronary computed tomography (CT)
      angiography. METHODS: This study was a retrospective cross-sectional study. A
      clinical model was derived from 2392 patients and verified by 733 patients who
      underwent coronary CT suspected of coronary artery disease. High-risk plaque was
      defined as a plaque with positive remodeling (remodeling index>1.1), low
      attenuation (<30Hounsfield units) and napkin-ring sign. The risk score was
      calculated from the following 6 variables with a maximum of 24 points: age, sex,
      hemoglobin A1c, systolic blood pressure, high-density lipoprotein and smoking
      status. RESULTS: The proportion of patients with high-risk plaque was 11% and 17%
      in the derivation and validation cohort, respectively. The area under the
      receiver operation characteristic curve was 0.71 (95% confidence interval (CI):
      0.68 to 0.74) in the derivation cohort and 0.75 (95% CI: 0.70 to 0.79) in the
      validation cohort. The frequency of high-risk plaques was 4% in the low-risk
      group (<=8 points) while it was 53% in the high-risk group (>=17 points) of the
      derivation cohort. CONCLUSIONS: We propose a scoring system to detect high-risk
      plaque assessed by coronary CT. Patients in the high-risk group have a high
      prevalence of high-risk plaque and might benefit from lipid lowering therapy.

PMID- 27865197
TI  - Efficacy and safety of ticagrelor versus clopidogrel with different dosage in
      high-risk patients with acute coronary syndrome.
AB  - BACKGROUND: Dual antiplatelet therapy is recommended as a standard antiplatelet
      strategy in acute coronary syndrome. For those with reduced pharmacologic
      response to clopidogrel, strengthening antiplatelet therapy (clopidogrel 150mg
      daily) may reduce adverse clinical events. Ticagrelor is a direct-acting
      inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset
      and offset than clopidogrel. METHODS: In this retrospective study, we compared
      ticagrelor (180mg loading dose 90mg twice daily thereafter), clopidogrel (300mg
      loading dose, 75mg or 150mg daily thereafter) for the prevention of
      cardiovascular events in 273 high-risk patients admitted to coronary care unit
      with acute coronary syndrome. RESULTS: The rate of IST in hospital was
      significantly reduced in patients of ticagrelor group comparing with those
      receiving clopidogrel 75mg (0.69% vs 8.2%, p=0.009). Moreover, the TVR rate was
      less in the ticagrelor group than clopidogrel 75mg group (2.7% vs 13.1%, p=0.007)
      6months follow-up. The incidence of MACCE has no difference between the two
      clopidogrel groups. Kaplan-Meier analysis of MACCE-free indicated that there was
      no difference between the three groups. Ticagrelor significantly increased the
      rate of minor bleeding compared with clopidogrel 75mg daily during hospital
      (45.5% vs 26.2%,p=0.012) and 6-month follow-up (66.9% vs 45.9%,p=0.004).Bleeding
      free prognosis was significantly better in the clopidogrel 75mg daily group.
      CONCLUSIONS: In patients with acute coronary syndrome undergoing PCI, the rate of
      in-stent thrombosis and TVR were significantly reduced treated with ticagrelor
      compared with clopidogrel 75mg daily, without an increase of overall major
      bleeding, but with an increase of minor bleeding.

PMID- 27865198
TI  - A propensity matched case-control study comparing efficacy, safety and costs of
      the subcutaneous vs. transvenous implantable cardioverter defibrillator.
AB  - BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICD) have
      become more widely available. However, comparisons with conventional transvenous
      ICDs (TV-ICD) are scarce. METHODS: We conducted a propensity matched case-control
      study including all patients that underwent S-ICD implantation over a five-year
      period in a single tertiary centre. Controls consisted of all TV-ICD implant
      patients over a contemporary time period excluding those with pacing indication,
      biventricular pacemakers and those with sustained monomorphic ventricular
      tachycardia requiring anti-tachycardia pacing. Data was collected on device
      related complications and mortality rates. A cost efficacy analysis was
      performed. RESULTS: Sixty-nine S-ICD cases were propensity matched to 69 TV-ICD
      controls. During a mean follow-up of 31+/-19 (S-ICD) and 32+/-21months (TV-ICD;
      p=0.88) there was a higher rate of device-related complications in the TV-ICD
      group predominantly accounted for by lead failures (n=20, 29% vs. n=6, 9%;
      p=0.004). The total mean cost for each group, including the complication-related
      costs was L9967+/-4511 ($13,639+/-6173) and L12,601+/-1786 ($17,243+/-2444) in
      the TV-ICD and S-ICD groups respectively (p=0.0001). Even though more expensive S
      ICD was associated with a relative risk reduction of device-related complication
      of 70% with a HR of 0.30 (95%CI 0.12-0.76; p=0.01) compared to TV-ICDs.
      CONCLUSIONS: TV-ICDs are associated with increased device-related complication
      rates compared to a propensity matched S-ICD group during a similar follow-up
      period. Despite the existing significant difference in unit cost of the S-ICD,
      overall S-ICD costs may be mitigated versus TV-ICDs over a longer follow-up
      period.

PMID- 27865200
TI  - A review of comparative studies of MitraClip versus surgical repair for mitral
      regurgitation.
AB  - OBJECTIVES: We summarized comparative studies of MitraClip versus surgical repair
      for mitral regurgitation (MR) with a systematic literature search and meta
      analytic estimates. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register
      of Controlled Trials were searched through June 2016. Eligible studies were
      randomized controlled or observational comparative studies of MitraClip versus
      surgical repair enrolling patients with MR and reporting early (30-day or in
      hospital) or late (>=6-month including early) all-cause mortality. For each
      study, data regarding all-cause mortality and incidence of recurrent >2+ MR in
      both groups were used to generate odds ratios (ORs). Alternatively, ORs or hazard
      ratios (HRs) for mortality and recurrent MR themselves were directly abstracted
      from each study. RESULTS: Eight reports of 7 studies comparing MitraClip with
      surgical repair enrolling a total of 1015 patients with MR were identified and
      included. Pooled analyses demonstrated significantly higher age and logistic
      European System of Cardiac Operative Risk Evaluation and significantly lower
      ejection fraction in the MitraClip than surgical repair group, no significant
      difference in rate of women and patients with New York Heart Association
      functional class of >II, no statistically significant difference in early- (OR,
      0.54; p=0.08) and late-mortality (HR/OR, 1.17; p=0.46), and significantly higher
      incidence of recurrent MR in the MitraClip than surgical repair group (HR/OR,
      4.80; p<0.00001). CONCLUSIONS: In patients with MR, the MitraClip procedure
      achieves similar survival to surgical MV repair despite higher risk profiles.
      Recurrent MR, however, occurs more frequently (4.8-fold) after the MitraClip than
      surgical repair.

PMID- 27865196
TI  - 'Browning' the cardiac and peri-vascular adipose tissues to modulate
      cardiovascular risk.
AB  - Excess visceral adiposity, in particular that located adjacent to the heart and
      coronary arteries is associated with increased cardiovascular risk. In the
      pathophysiological state, dysfunctional adipose tissue secretes an array of
      factors modulating vascular function and driving atherogenesis. Conversely, brown
      and beige adipose tissues utilise glucose and lipids to generate heat and are
      associated with improved cardiometabolic health. The cardiac and thoracic
      perivascular adipose tissues are now understood to be composed of brown adipose
      tissue in the healthy state and undergo a brown-to-white transition i.e. during
      obesity which may be a driving factor of cardiovascular disease. In this review
      we discuss the risks of excess cardiac and vascular adiposity and potential
      mechanisms by which restoring the brown phenotype i.e. "re-browning" could
      potentially be achieved in clinically relevant populations.

PMID- 27865199
TI  - CHA2DS2-VASC-AF2 score accurately predicts moderate-to-severe acute neurological
      dysfunction in the course of first ever ischaemic stroke.

PMID- 27865201
TI  - Increased risk of ventricular tachycardia in patients with sarcoidosis during the
      very long term follow-up.
AB  - BACKGROUND: Sarcoidosis is an important diagnostic consideration in patients with
      ventricular tachycardia (VT) of unknown origin. The clinical course of VT as the
      primary presentation in patients with sarcoidosis is mostly unknown. This study
      aimed to investigate the incidence of life-threatening VT and mortality during
      long term follow-up in patients with sarcoidosis. METHODS: We analyzed the
      epidemiological features of sarcoidosis in Taiwan using the National Health
      Insurance Research Database from 2000 to 2004. Patients with sarcoidosis were
      identified, and healthy controls without prior histories of structural heart
      disease were matched with a 1:1 propensity-score to the sarcoidosis group. The
      risk of life-threatening VT and mortality with sarcoidosis was analyzed. RESULTS:
      A total of 2237 sarcoidosis cases were enrolled with a matching number of healthy
      controls, and the baseline characteristics between the two groups were similar.
      After a mean follow-up of 11.4+/-2.15years (IQR: 12, 11.3-12), the VT incidence
      in the sarcoidosis group was higher than in healthy controls (0.94% [85 per
      100,000 person-year] in the sarcoidosis group, and 0.09% [8 per 100,000 person
      year] in healthy controls). After a multivariate adjustment including the sex,
      age, and other comorbidities, the VT risk was still higher in the sarcoidosis
      group (hazard ratio: 12.7, 95% confidence interval: 2.82-56.9; P<0.001). The risk
      of defibrillator implantations for secondary prevention, cardiovascular death,
      and total mortality between the groups was equivalent. CONCLUSIONS: Sarcoidosis
      may increase the predisposition to ventricular arrhythmias with a cumulative
      incidence of 0.94% during a very long term follow-up of nearly 10years from
      initially diagnosing sarcoidosis.

PMID- 27865202
TI  - Compulsive exercise as a mediator between clinical perfectionism and eating
      pathology.
AB  - The aim of this study was to examine whether compulsive exercise mediates the
      relationship between clinical perfectionism and eating pathology, based on the
      cognitive behavioral model of compulsive exercise. Participants were 368 adults
      who participated regularly in sport/exercise and completed online measures of
      perfectionism, compulsive exercise and eating disorders. In support of the well
      established link between perfectionism and eating disorders, clinical
      perfectionism predicted eating pathology both directly and indirectly mediated by
      compulsive exercise. In addition, there were also direct effects of clinical
      perfectionism on the avoidance/rule-driven behavior, weight control, and mood
      improvement subscales of the Compulsive Exercise Test (CET). There was a direct
      effect of the CET weight control subscale on eating pathology and a negative
      direct effect of the CET subscale mood improvement on eating pathology. Findings
      lend support to the cognitive behavioral model of compulsive exercise in which
      clinical perfectionism is conceptualized as related to eating disorders directly
      and indirectly through the mediation of compulsive exercise. Compulsive exercise
      was also found to have a direct effect on eating disorders. Compulsive exercise
      may be a symptom of eating pathology, rather than an antecedent, however causal
      inferences could not be established given the correlational design. Longitudinal
      research using cross-lagged panel designs to examine a bidirectional relationship
      between compulsive exercise and eating disorders is needed.

PMID- 27865203
TI  - Minocycline prevents cerebral malaria, confers neuroprotection and increases
      survivability of mice during Plasmodium berghei ANKA infection.
AB  - Cerebral malaria (CM) is a neurological complication arising due to Plasmodium
      falciparum or Plasmodium vivax infection. Minocycline, a semi-synthetic
      tetracycline, has been earlier reported to have a neuroprotective role in several
      neurodegenerative diseases. In this study, we investigated the effect of
      minocycline treatment on the survivability of mice during experimental cerebral
      malaria (ECM). The currently accepted mouse model, C57BL/6 mice infected with
      Plasmodium berghei ANKA, was used for the study. Infected mice were treated with
      an intra-peritoneal dose of minocycline hydrochloride, 45mg/kg daily for ten days
      that led to parasite clearance in blood, brain, liver and spleen on 7th day post
      infection; and the mice survived until experiment ended (90days) without parasite
      recrudescence. Evans blue extravasation assay showed that blood-brain barrier
      integrity was maintained by minocycline. The tumor necrosis factor-alpha protein
      level and caspase activity, which is related to CM pathogenesis, was
      significantly reduced in the minocycline-treated group. Fluoro-Jade(r) C and
      hematoxylin-eosin staining of the brains of minocycline group revealed a decrease
      in degenerating neurons and absence of hemorrhages respectively. Minocycline
      treatment led to decrease in gene expressions of inflammatory mediators like
      interferon-gamma, CXCL10, CCL5, CCL2; receptors CXCR3 and CCR2; and hence
      decrease in T-cell-mediated cerebral inflammation. We also proved that this
      reduction in gene expressions is irrespective of the anti-parasitic property of
      minocycline. The distinct ability of minocycline to modulate gene expressions of
      CXCL10 and CXCR3 makes it effective than doxycycline, a tetracycline used as
      chemoprophylaxis. Our study shows that minocycline is highly effective in
      conferring neuroprotection during ECM.

PMID- 27865204
TI  - Possible role of transforming growth factor beta in tuberculous meningitis.
AB  - BACKGROUND: Transforming growth factor beta (TGF-beta) is an anti-inflammatory
      cytokine and its role in hydrocephalus and stoke has been suggested. Tuberculous
      meningitis (TBM) is associated with exudates, stroke, hydrocephalus and
      tuberculoma, but the role of TGF-beta has not been evaluated in relation to these
      changes. AIM: To evaluate the cerebrospinal fluid (CSF) TGF-beta level in the
      patients with TBM, and correlate these with clinical findings, MRI changes,
      paradoxical response and outcome at 6months. METHODS: TBM patients diagnosed on
      the basis of clinical, CSF and MRI criteria were prospectively included. The
      clinical details including duration of illness, seizures, focal motor deficit,
      Glasgow Coma Scale (GCS) score and stage of TBM were noted. Presence of exudate,
      hydrocephalus, tuberculoma and infarction in MRI was also noted. MRI was repeated
      at 3months and presence of paradoxical response was noted. Cerebrospinal fluid
      TGF-beta was measured using ELISA on admission and repeated at 3months and these
      were compared with 20 controls. RESULTS: TGF-beta level was significantly higher
      in TBM compared to the controls (385.76+/-249.98Vs 177.85+/-29.03pg/ml,
      P<0.0001). TGF-beta correlated with motor deficit, infarction and tuberculoma on
      admission but did not correlate with CSF abnormalities, drug induced hepatitis,
      paradoxical response and outcome. TGF-beta level at 3months was significantly
      lower than the baseline but remained higher than the controls. CONCLUSION: CSF
      TGF-beta levels are elevated in TBM and correlate with infarction and
      tuberculoma.

PMID- 27865205
TI  - Human hepatic stellate cells and inflammation: A regulated cytokine network
      balance.
AB  - AIM: Uncertainty about the safety of cell therapy continues to be a major
      challenge to the medical community. Inflammation and the associated immune
      response represent a major safety concern hampering the development of long-term
      clinical therapy. In vivo interactions between the cell graft and the host immune
      system are mediated by functional environmental sensors and stressors that play
      significant roles in the immunobiology of the graft. Within this context, human
      liver stellate cells (HSC) demonstrated marked immunological plasticity that has
      main importance for future liver cell therapy application. METHODS: By using qPCR
      technique, we established the cytokine gene expression profile of HSCs and
      investigated the effect of an inflammatory environment on the immunobiology of
      HSCs. RESULTS AND DISCUSSION: HSCs present a specific immunological profile as
      demonstrated by the expression and modulation of major immunological cytokines.
      Under constitutive conditions, the cytokine pattern expressed by HSCs was
      characterized by the high expression of IL-6. Inflammation critically modulated
      the expression of major immunological cytokines. As evidenced by the induction of
      the expression of several inflammatory genes, HSCs acquire a pro-inflammatory
      profile that ultimately might have critical implications for their immunological
      shape. CONCLUSION: These new observations have to be taken into account in any
      future liver cell therapy application based on the use of HSCs.

PMID- 27865206
TI  - Humor and preschoolers' trust: Sensitivity to changing intentions.
AB  - This research demonstrates that preschoolers (a) avoid trusting informants with
      humorous intentions when learning novel information and (b) flexibly consider
      current intentions rather than initial intentions when determining who to trust.
      In Study 1 (N=61), 3- and 4-year-olds based their trust on intentions or
      intentional cues alone, trusting a sincere informant over a joker, even when no
      prior accuracy or inaccuracy was displayed. In Study 2 (N=32), 3- and 4-year-olds
      flexibly based their trust on the informants' current intentions or intentional
      cues rather than their initial ones. Children trusted a sincere informant, who
      originally joked, over a joker, who was originally sincere. In Study 3 (N=89), 3
      , 4-, and 5-year-olds tracked changing intentions, and not just intentional cues,
      in determining who to trust. Children trusted an informant who joked during
      training trials but was sincere during test trials over an informant who was
      ignorant during training trials and was sincere during test trials. However, if
      the ignorant informant became knowledgeable and the joker continued to joke, the
      pattern reversed. This is the first study to show that preschoolers consider
      intentions to joke when learning information. This is also the first study to
      show that preschoolers do not see trust as stable but rather see it as a function
      of changing intentions.

PMID- 27865208
TI  - What evolution tells us about protein physics, and protein physics tells us about
      evolution.
AB  - The integration of molecular evolution and protein biophysics is an emerging
      theme that steadily gained importance during the last 15 years, significantly
      advancing both fields. The central integrative concept is the stability of the
      native state, although non-native conformations are increasingly recognized to
      play a major role, concerning, for example, aggregation, folding kinetics, or
      functional dynamics. Besides molecular requirements on fitness, the stability of
      native and alternative conformations is modulated by a variety of factors,
      including population size, selective pressure on the replicative system, which
      determines mutation rates and biases, and epistatic effects. We discuss some of
      the recent advances, open questions, and integrating views in protein evolution,
      in light of the many underlying trade-offs, correlations, and dichotomies.

PMID- 27865207
TI  - A multi-level comparative analysis of human femoral cortical bone quality in
      healthy cadavers and surgical safe margin of osteosarcoma patients.
AB  - Osteosarcoma is the most common primary malignancy of bone. However, the
      potential variation it brings to the adjacent undamaged bone tissue is seldom
      investigated. In this study, we conducted a multi-level comparison of human
      femoral cortical bone quality in healthy cadavers (aged 42+/-11 years) and in
      resected safe margin of osteosarcoma patients (aged 49+/-15 years). The objective
      of this study was to document the changes with exposure to osteosarcoma condition
      in bone mechanical strength, structural morphology and elementary composition,
      evaluated by static and dynamic mechanical analysis (DMA), scanning electron
      microscopy (SEM) imaging, X-ray diffraction (XRD) and Fourier-transform infrared
      spectroscopy (FTIR). The resected clinical samples from healthy and osteosarcoma
      conditioned bones were grouped into the Tumor and Healthy groups, and shaped into
      regular beam specimens or pulverized according to testing protocols. The results
      of mechanical tests confirmed osteolytic deteriorations in mineral phase of the
      Tumor group, in terms of significant reductions in storage modulus (-53.6%, at
      1Hz), bending strength (-53.0%) and stiffness (-64.8%) as compared to the Healthy
      group. However, the energy dissipation/absorption ability of the collagen phase
      in the Tumor group did not differ from the Healthy group statistically. Although
      specimens showed no visible morphological difference, a decline in osteocyte
      lacunar density in bone specimens from the Tumor group was discovered (-54.4%,
      p<0.001). Higher magnification observation showed that the cell-free lacunae in
      the Tumor group were occluded by randomized overgrown collagen fibers. XRD and
      FTIR analysis further demonstrated a lower hydroxyapatite crystallinity and
      decreased mineral:matrix ratio in pulverized samples from the Tumor group, mainly
      due to the prominent Amide peaks. Taken together, these data revealed a
      previously unrecognized effect of osteosarcoma on the adjacent "normal" bone
      quality. The current study may provide insights on bone tumor pathology and an
      advanced understanding of surgical safe margin.

PMID- 27865209
TI  - Protein function machinery: from basic structural units to modulation of
      activity.
AB  - Contemporary protein structure is a result of the trade off between the laws of
      physics and the evolutionary selection. The polymer nature of proteins played a
      decisive role in establishing the basic structural and functional units of
      soluble proteins. We discuss how these elementary building blocks work in the
      hierarchy of protein domain structure, co-translational folding, as well as in
      enzymatic activity and molecular interactions. Next, we consider modulators of
      the protein function, such as intermolecular interactions, disorder-to-order
      transitions, and allosteric signaling, acting via interference with the protein's
      structural dynamics. We also discuss the post-translational modifications, which
      is a complementary intricate mechanism evolved for regulation of protein
      functions and interactions. In conclusion, we assess an anticipated contribution
      of discussed topics to the future advancements in the field.

PMID- 27865210
TI  - Exophytic Verrucous Hyperplasia of the Oral Cavity - Application of Standardized
      Criteria for Diagnosis from a Consensus Report
AB  - Verruco-papillary lesions (VPLs) of the oral cavity described in the literature
      involve a spectrum of conditions including squamous papilloma, verruca vulgaris,
      focal epithelial hyperplasia, condyloma, proliferative verrucousleukoplakia and
      verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature
      and have aviral aetiology. Virus associated benign mucosal outgrowths are not too
      difficult to diagnose either clinically orby microscopy. Apart from virus
      associated lesions, VPLs harboring malignant potential or behaviour such
      asverrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous
      hyperplasia (OVH), oral papillarysquamous cell carcinoma (PSCC) and oral
      conventional squamous cell carcinoma with papillary features (CSCC)need to be
      further clarified for better understanding of their predictable biologic behavior
      and appropriatetreatment. Current understanding of potentially malignant VPLs is
      perplexing and is primarily attributed tothe use of confusing and unsatisfactory
      terminology. In particular, the condition referred to as oral
      verrucoushyperplasia (OVH) poses a major diagnostic challenge. OVH represents a
      histopathological entity whose clinicalfeatures are not well recognised and is
      usually clinically indistinguishable from a verrucous carcinoma and aPSCC or a
      CSCC. A consensus report published by an expert working group from South Asia as
      an outcome ofthe 'First Asian Regional Meeting on the Terminology and Criteria
      for Verruco-papillary Lesions of the OralCavity' held in Kuala Lumpur, Malaysia,
      recognised the clinical description of these OVH as a new entity named'Exophytic
      Verrucous Hyperplasia'. Previously described clinical features of OVH such as the
      'blunt' or 'sharp'variants; and the 'mass' or 'plaque' variants can now
      collectively fall under this newly described entity. This paperdiscusses in
      detail the application of the standardized criteria guidelines of 'Exophytic
      Verrucous Hyperplasia'as published by the expert group which will enable
      clinicians and pathologists to uniformly interpret their poolof OVH cases and
      facilitate a better understanding of OVH malignant potential.

PMID- 27865211
TI  - The time is now: setting a rural health research agenda.

PMID- 27865212
TI  - Changes in the oral health of the children of Dili, Timor Leste, between 2002 and
      2014.
AB  - INTRODUCTION: This research compared the oral health status of school children in
      Dili (the capital of Timor Leste) in 2002 and 2014. METHODS: The 2014 oral health
      survey of Dili's children replicated the methods of an AusAID-supported oral
      health survey conducted in 2002. Equal numbers of children were invited to
      participate from four age groups (6-8, 9-11, 12-14 and 15-17 years). For the 2014
      survey, the subdistricts of Dom Aleixo, Cristo Rei, Metinaro and Vera Cruz were
      randomly selected for inclusion. A questionnaire was used to collect data on
      demographics and oral health behaviours. Oral epidemiological examinations were
      conducted by four dentists and five dental nurses. RESULTS: The 2014 survey in
      Dili recruited 758 participants for the questionnaire and 655 children for the
      oral examination. In 2014, a lower proportion of children reported brushing their
      teeth the previous day (97% vs 100%, <i>p</i>=0.01) and a larger proportion
      reported having toothache (40% vs 19%, <i>p</i><0.001) (sometimes to very often)
      during the previous 12 months. The mean number of decayed, missing or filled
      teeth in the primary plus permanent dentition (dmft + DMFT) was greater in 2014
      than in 2002 (4.2 vs 3.5, <i>p</i>=0.01). There was no difference in the
      prevalence of decay in the primary dentition (39% vs 37%, <i>p</i>=0.61) or the
      mean number of decayed, missing or filled (dmft) teeth in the primary dentition
      in 2014 compared to 2002 (2.0 vs 1.8, <i>p</i>=0.47). However, the prevalence of
      decay in the permanent dentition was greater in 2014 (70% vs 53%, <i>p</i><0.001)
      as was the mean DMFT (2.3 vs 1.7, <i>p</i>=0.04). The prevalence of gingival
      bleeding (65% vs 81%, <i>p</i><0.001) and calculus (57% vs 86%, <i>p</i><0.001)
      was lower in 2014. CONCLUSIONS: There was an increase in dental caries
      experiences in Dili school children between 2002 and 2014, associated with more
      permanent teeth dental caries experiences.

PMID- 27865214
TI  - [Auditory Neuropathy: Clinical Evaluation and Diagnostic Approach].
AB  - INTRODUCTION: Auditory neuropathy is a condition in which there is a change in
      the neuronal transmission of the auditory stimuli. Our objective was to describe
      the patients' series within the clinical spectrum of auditory neuropathy.
      MATERIAL AND METHODS: We designed a transversal, retrospective study, with a
      description of a consecutive case series. Auditory neuropathy was defined by the
      presence of acoustic otoemissions plus absent/abnormal auditory brainstem
      responses with cochlear microphonism. RESULTS: 34 patients with bilateral hearing
      loss, 23 males and 11 females, were included in the study. Eighty percent of the
      cases had congenital onset of hearing loss. Acoustic otoemissions were absent in
      67% of them. Cochlear microfonism was present in 79% of all cases. Prenatal,
      perinatal or ambiental factors were present in 35.2% of the cases. DISCUSSION:
      Medical literature shows great variability in findings related to auditory
      neuropathy, both in its etiology and epidemiological data. CONCLUSION: Auditory
      neuropathy presents a broad spectrum of changes that may result from mild to
      severe changes in the functioning of the auditory pathway, and in our sample we
      observed that 80% of Auditory neuropathy have congenital onset of hearing loss
      and/or with cochlear microphonism identified. 91% of patients experience
      significant hearing impairment and 53% suffer from severe or profound deafness.

PMID- 27865213
TI  - Phenotypic correction of Fanconi anemia cells in the murine bone marrow after
      carrier cell mediated delivery of lentiviral vector.
AB  - Fanconi anemia (FA) is an autosomal-recessive disorder associated with
      hematopoietic failure and it is a candidate for hematopoietic stem cell (HSC)
      directed gene therapy. However, the characteristically reduced HSC numbers found
      in FA patients, their ineffective mobilization from the marrow, and re
      oxygenation damage during ex vivo manipulation have precluded clinical success
      using conventional in vitro approaches. We previously demonstrated that
      lentiviral vector (LV) particles reversibly attach to the cell surface where they
      gain protection from serum complement neutralization. We reasoned that cellular
      delivery of LV to the bone marrow niche could avoid detrimental losses during FA
      HSC mobilization and in vitro modification. Here, we demonstrate that a VSV-G
      pseudotyped lentivector, carrying the FANCC transgene, can be transmitted from
      carrier to bystander cells. In cell culture and transplantation models of FA, we
      further demonstrate that LV carrier cells migrate along SDF-1alpha gradients and
      transfer vector particles that stably integrate and phenotypically correct the
      characteristic DNA alkylator sensitivity in murine and human FA-deficient target
      bystander cells. Altogether, we demonstrate that cellular homing mechanisms can
      be harnessed for the functional phenotype correction in murine FA hematopoietic
      cells.

PMID- 27865215
TI  - [Study of the Sociodemographic Factors and Risky Behaviours Associated with the
      Acquisition of Sexual Transmitted Infections by Foreign Exchange Students in
      Portugal].
AB  - BACKGROUND: Sexual transmitted infections are a main cause of morbidity, being a
      public health problem due to its reproductive complications, mostly observed in
      teenagers and young adults. The purpose of this study was to evaluate
      sociodemographic factors and risky behaviours associated with sexual transmitted
      infections acquisition and to assess personal awareness of risky behaviour and
      the knowledge about Chlamydia trachomatis infection between foreign exchange
      students in Portugal. MATERIAL AND METHODS: The main instrument for data
      collection was a questionnaire, applied to foreign students in university
      exchange in Portugal, during the years 2012/2013, 2013/2014 e 2014/2015 Results:
      Three hundred and thirty eight (338) questionnaires were evaluated, being 58.3%
      female students, aged between 17 and 30 years old. Mean age for the beginning of
      the sexual activity was 17.5 years old and the mean number of lifetime sexual
      partners was 6.9. Concerning the answers given: 11.8% mentioned a sexual
      relationship with the same gender, 9.5% mentioned that they have never done oral
      sex and 29% assumed they had practiced anal sex; 82.1% mentioned alcohol/drugs
      consumption; 21% did not know that Sexual transmitted infections can be
      transmitted through oral sex and 42.3% did not recognize Chlamydia trachomatis as
      an Sexual transmitted infections agent. DISCUSSION: Although sexual transmitted
      infections can affect individuals of all ages, races and sexual orientation,
      various demographic, social and behavioral factors have revealed influence in
      their prevalence rates. CONCLUSION: Despite knowing about sexual transmitted
      infections, these students maintain sexual risky behaviours, mainly early age for
      starting sexual activity, multiple sexual partners and the absence of protection
      during sexual activities.

PMID- 27865216
TI  - Establishing the Role of Unlinked Total Elbow Arthroplasty in Low Demand
      Patients: A Long-Term Follow-up Study.
AB  - INTRODUCTION: Experience with total elbow arthroplasty is scarce in most centers.
      It seems to have a significant rate of associated complications. Most studies are
      based on non-validated outcome measures and short-term results. MATERIAL AND
      METHODS: We selected patients undergoing unlinked total elbow arthroplasty, with
      a resultant sample of thirteen cases, with a mean postoperative follow-up of 72
      months. We applied the Mayo Elbow Score and all patients underwent an X-ray
      study, prior to surgery and during the follow-up period. RESULTS: All patients
      have a systemic inflammatory condition. The mean Mayo score increased from 43
      points preoperatively to 70 and 80 points at the intermediate follow-up period
      (with a mean of 15 months after the operation) and at the time of the latest
      follow-up evaluation (with a mean of 72 months after the operation). There was an
      increase in range of motion in all cases. There was one case of mechanical
      failure and two cases of transient ulnar neuropathy. DISCUSSION: Elbow
      dysfunction causes great loss in patient's quality of life, incapacitating them
      for the simplest activities. Small improvements in range of motion and pain
      relief result in significant changes in the patient's functional ability. There
      is a demand to clarify the performance of total elbow arthroplasty in selected
      patient groups in order to throw more light on the relative roles of the
      available implants. CONCLUSIONS: The results obtained in this study seem to
      confirm the long-term benefit of the unlinked arthroplasty in severe joint
      dysfunction in patients with low physical demand, particularly in rheumatoid
      arthritis, a common and limiting condition in our population.

PMID- 27865217
TI  - [Multidimensional Strategy Regarding the Reduction of Central-Line Associated
      Infection in Pediatric Intensive Care].
AB  - INTRODUCTION: To determine the central-line associated bloodstream infection rate
      after implementation of central venous catheter-care practice bundles and
      guidelines and to compare it with the previous central-line associated
      bloodstream infection rate. MATERIAL AND METHODS: A prospective, longitudinal,
      observational descriptive study with an exploratory component was performed in a
      Pediatric Intensive Care Unit during five months. The universe was composed of
      every child admitted to Pediatric Intensive Care Unit who inserted a central
      venous catheter. A comparative study with historical controls was performed to
      evaluate the result of the intervention (group 1 versus group 2). RESULTS:
      Seventy five children were included, with a median age of 23 months: 22 (29.3%)
      newborns; 28 (37.3%) with recent surgery and 32 (43.8%) with underlying illness.
      A total of 105 central venous catheter were inserted, the majority a single
      central venous catheter (69.3%), with a mean duration of 6.8 +/- 6.7 days. The
      most common type of central venous catheter was the short-term, non-tunneled
      central venous catheter (45.7%), while the subclavian and brachial flexure veins
      were the most frequent insertion sites (both 25.7%). There were no cases of
      central-line associated bloodstream infection reported during this study.
      Comparing with historical controls (group 1), both groups were similar regarding
      age, gender, department of origin and place of central venous catheter insertion.
      In the current study (group 2), the median length of stay was higher, while the
      mean duration of central venous catheter (excluding peripherally inserted central
      line) was similar in both groups. There were no statistical differences regarding
      central venous catheter caliber and number of lumens. Fewer children admitted to
      Pediatric Intensive Care Unit had central venous catheter inserted in group 2,
      with no significant difference between single or multiple central venous
      catheter. DISCUSSION: After multidimensional strategy implementation there was no
      reported central-line associated bloodstream infection Conclusions: Efforts must
      be made to preserve the same degree of multidimensional prevention, in order to
      confirm the effective reduction of the central-line associated bloodstream
      infection rate and to allow its maintenance.

PMID- 27865218
TI  - [Percutaneous Endovascular Aortic Repair with Local Anesthesia - One Day
      Surgery].
AB  - INTRODUCTION: To evaluate the results of the abdominal aortic aneurism
      endovascular treatment (EVAR), percutaneously and with local anesthesia,
      according to the concept of one day surgery. MATERIAL AND METHODS: Unicentric,
      retrospective analysis of patients with aorto-iliac aneurysmal disease,
      consecutively treated by EVAR with percutaneous access trough the Preclose
      technique (pEVAR), according to the outpatient criteria, with one overnight stay
      in the hospital. The technical success, exclusion of the aneurysmal sac,
      endoleak, re-intervention and mortality were evaluated. RESULTS: Twenty
      consecutive patients (all male; mean age 74.65 years) were treated by EVAR with
      percutaneous access and local anesthesia, from which 95% (19) presented with
      abdominal aortic aneurysm and 5% (1) common iliac aneurysm. All implants were
      sucessfully performed, with an initial endoleak rate of 10% (2), determined by
      one type 1a endoleak successfully corrected intra-operatively and one type 2a
      endoleak diagnosed in the first imaging control, which sealed spontaneously on
      the second control. Initial technical success for percutaneous closure was 97.5%,
      with one case reported of femoral pseudo-aneurism, posteriorly treated by
      percutaneous thrombin injection. Median length of stay was one day [1-10], with a
      mean follow-up of 11.4 months [1-36]. Both the re-intervention and mortality rate
      are 0% for the selected period. CONCLUSION: Our one day surgery model for the
      outpatient treatment of abdominal aortic aneurysm by the pEVAR technique is
      innovative, safe and effective, as long as the selection criteria are respected.

PMID- 27865219
TI  - HIV/AIDS Indicators for Clinical Care Quality Assessment: Relevance and Utility
      Assessed by Health Professionals.
AB  - INTRODUCTION: After conducting a systematic review of quality indicators for
      assessing HIV/AIDS clinical care, we aimed to assess the clinical relevance and
      practice utility of those indicators from the point of view of HIV/AIDS physician
      experts. MATERIAL AND METHODS: This is an observational, cross-sectional study,
      in which we selected, by convenience, physicians who work in an Infectious
      Disease Department of a central hospital to complete two questionnaires with a
      core set of indicators to establish the most relevant and useful indicators for
      assessment of the clinical HIV/AIDS care. A Likert scale was used to rank the
      indicators. RESULTS: Eleven of thirteen physicians filled two questionnaires.
      From the initial list of 53 quality indicators, 21 were identified as the most
      relevant and useful in HIV/AIDS clinical care. The internal consistency for
      clinical relevance in each indicators domain was for clinical signs and symptoms
      (p = 0.971), for therapy (p = 0.900), for prognosis (p = 0.820) and diagnosis (p
      = 0.733) and for practice utility were diagnosis (p = 0.934), clinical signs (p =
      0.964), laboratory examinations (p = 0.947), therapy (p = 0.583) and prognosis (p
      = 0.368). DISCUSSION: In the process of assessing the clinical relevance and
      practice utility of HIV/AIDS quality care indicators, it was found that the
      majority of physicians agreed that diagnosis and clinical symptoms and signs
      indicators domains are the most important for assessing the quality of care for
      HIV/AIDS patients. CONCLUSION: This instrument should be considered as a
      diagnostic tool, allowing hospital administrators to identify if HIV/AIDS care is
      properly delivered or needs improvement.

PMID- 27865220
TI  - [Efficacy of the Vaccines Against Human Papillomavirus in Women Older than 24
      Years in the Cervix Cancer Prevention].
AB  - INTRODUCTION: Cervix cancer is the fourth most common female cancer and the
      second most frequent in women aged 15 to 44 years. The infection by the human
      papillomavirus is a necessary condition in almost all of cervix cancer cases; it
      is a sexually transmitted disease and all women sexually active are at risk of
      being infected. There are currently three vaccines against human papillomavirus,
      and despite of the efficacy being well proven in woman aged up to 25 years, it is
      not well established in older ages. MATERIAL AND METHODS: It was performed a
      literature review of the current evidence about the efficacy of the vaccines
      against human papillomavirus in women older than 24 years in the cervix cancer
      prevention, and was assessed the evidence quality by the GRADE system. RESULTS:
      Two randomized controlled trials were identified with a total of 9,571
      participants - 4,792 vaccinated and 4,779 at the control group and reported data
      of 48 months period follow-up. The relative risk reduction was 41% (95% CI: 29 a
      50%) - for the vaccinated group. There were no differences in safety and
      tolerability between the two groups - vaccine and control. CONCLUSION: The actual
      evidence shows that the vaccines against human papillomavirus 16 and/or 18 in
      women older than 24 until 45 years have an important efficacy at reducing the
      risk of having persistent infection and/or to acquire cervix cancer precursor
      lesions.

PMID- 27865221
TI  - [Massive Upper Airway Bleeding: A Rare Case of Aortobronchial Fistula].
AB  - Clinical presentation of haemoptysis and haematemesis often generates confusion,
      becoming a difficult task to determine the source of upper airway bleeding.
      Aortobronchial fistula is a rare entity, but has been a reported complication in
      patients that have undergone aortic vascular surgery. A high clinical suspicion
      is fundamental to making this diagnosis. A 69 year old male, with a previous
      diagnosis of chronic gastritis, is admitted to the emergency room for vomiting
      blood. In the first 24 hours after admission, the patient develops respiratory
      insufficiency after an episode of massive bleeding from his mouth. A computed
      tomography is performed, which shows a descending thoracic aortic aneurism and
      signs of aortobronchial fistula. Urgent thoracic endovascular repair was
      performed. Early symptoms of aortobronchial fistulae are nonspecific which
      complicates the diagnosis and can lead to treatment delay. The use of
      bronchoscopy in these cases is controversial.

PMID- 27865222
TI  - Endometrial Tuberculosis Simulating an Ovarian Cancer: a case report.
AB  - Female genital tuberculosis remains a major health problem in developing
      countries and is an important cause of infertility. As symptoms, laboratory data
      and physical findings are non-specific, its diagnosis can be difficult. We
      describe a case of a 39-year-old woman suffering from peri-umbilical pain and
      increased abdominal size for one year, anorexia, asthenia, weight loss,
      occasionally dysuria and dyspareunia, and four months amenorrhea. Laboratory data
      revealed cancer antigen 125 (CA-125) level of 132.3 U/mL, erythrocyte
      sedimentation rate of 42 mm/h, and gamma-globulins of 2.66 g/dL. Computed
      tomography scan showed loculated ascites. It was initially suspected a
      carcinomatous origin, but ascites evaluation was negative for malignant cells.
      Magnetic resonance imaging from another hospital showed endometrial
      heterogeneity. Therefore, an endometrial biopsy was performed demonstrating an
      inflammatory infiltrate with giant cells of type Langhans and bacteriological
      culture identified Mycobacterium tuberculosis.

PMID- 27865223
TI  - Pyogenic Granuloma in a Patient on Gefitinib.

PMID- 27865224
TI  - [Penile Squamous Cell Carcinoma].

PMID- 27865225
TI  - Reactions of protective service workers towards people who stutter.
AB  - PURPOSE: This study sought to assess whether protective service workers differ
      from people in non-protective services occupations in their intended reactions
      towards people who stutter (PWS). METHODS: Analyses were based on questionnaire
      responses regarding intended reactions toward PWS from 171 protective services
      workers and 2595 non-protective services workers in the United States. A
      propensity score matching procedure was used to identify a comparison group of
      non-protective services workers for the protective services workers. The matching
      covariate variables included age, gender, years of education, familiarity with
      PWS, and beliefs about PWS. RESULTS: Findings indicated that protective services
      workers had less helpful intended behavioral reactions and more negative
      affective reactions towards PWS than the matched non-protective services workers.
      Examination of the matching covariate variables in the larger sample also
      indicated that protective services workers had less accurate beliefs about PWS
      compared to respondents not in protective services professions. CONCLUSION: Less
      favorable intended reactions of protective services workers toward PWS indicate a
      need for protective services workers to receive training in best practices when
      interacting with PWS.

PMID- 27865226
TI  - An investigation of the effects of a speech-restructuring treatment for
      stuttering on the distribution of intervals of phonation.
AB  - PURPOSE: The purpose of this study was to investigate whether stuttering
      reductions following the instatement phase of a speech-restructuring treatment
      for adults were accompanied by reductions in the frequency of short intervals of
      phonation (PIs). The study was prompted by the possibility that reductions in the
      frequency of short PIs is the mechanism underlying such reductions in stuttering.
      METHOD: The distribution of PIs was determined for seven adults who stutter,
      before and immediately after the intensive phase of a speech-restructuring
      treatment program. Audiovisual recordings of conversational speech were made on
      both assessment occasions, with PIs recorded with an accelerometer. RESULTS: All
      seven participants had much lower levels of stuttering after treatment but these
      were associated with reductions in the frequency of short PIs for only four of
      them. For the other three participants, two showed no change in frequency of
      short PIs, while for the other participant the frequency of short PIs actually
      increased. CONCLUSIONS: Stuttering reduction with speech-restructuring treatment
      can co-occur with reduction in the frequency of short PIs. However, the latter
      does not appear necessary for this reduction in stuttering to occur. Thus, speech
      restructuring treatment must have other, or additional, treatment agents for
      stuttering to reduce.

PMID- 27865227
TI  - Behavioural, emotional and social development of children who stutter.
AB  - PURPOSE: Developmental stuttering may be associated with diminished psychological
      well-being which has been documented from late childhood onwards. It is important
      to establish the point at which behavioural, emotional and social problems emerge
      in children who stutter. METHODS: The study used data from the Millennium Cohort
      Study, whose initial cohort comprised 18,818 children. Analysis involved data
      collected when the cohort members were 3, 5 and 11 years old. The association
      between parent-reported stuttering and performance on the Strengths and
      Difficulties Questionnaire was determined in regression analyses which controlled
      for cohort members' sex, verbal and non-verbal abilities, maternal education, and
      family economic status. RESULTS: Compared with typically-developing children,
      those who stuttered had significantly higher Total Difficulties scores at all
      three ages; in addition, scores on all of the sub-scales for 5-year-olds who
      stuttered indicated poorer development than their peers, and 11-year-olds who
      stuttered had poorer development than peers in all areas except prosocial skills.
      At ages 5 and 11, those who stuttered were more likely than peers to have scores
      indicating cause for clinical concern in almost all areas. CONCLUSION: Children
      who stutter may begin to show impaired behavioural, emotional and social
      development as early as age 3, and these difficulties are well established in
      older children who stutter. Parents and practitioners need to be aware of the
      possibility of these difficulties and intervention needs to be provided in a
      timely fashion to address such difficulties in childhood and to prevent the
      potential development of serious mental health difficulties later in life.

PMID- 27865228
TI  - Specific subtype of fluency disorder affecting French speaking children: A
      phonological analysis.
AB  - PURPOSE: Clinicians working with fluency disorders sometimes see children whose
      word repetitions are mostly located at the end of words and do not induce
      physical tension. Prior studies on the topic have proposed several names for
      these disfluencies including "end word repetitions", "final sound repetitions"
      and "atypical disfluency". The purpose of this study was to use phonological
      analysis to explore the patterns of this poorly recognized fluency disorder in
      order to better understand its specific speech characteristics. METHODS: We
      analyzed a spontaneous language sample of 8 French speaking children. Audio and
      video recordings allowed us to study general communication issues as well as
      linguistic and acoustical data. RESULTS: We did not detect speech rupture or
      coarticulation failures between the syllable onset and rhyme. The problem resides
      primarily on the rhyme production with a voicing interruption in the middle of
      the syllable nucleus or a repetition of the rhyme (nucleus alone or nucleus and
      coda), regardless of the position in the word or phrase. CONCLUSION: The present
      study provides data suggesting that there exist major differences in syllable
      production between the disfluencies produced by our 8 children and stuttered
      disfluencies. Consequently, we believe that this fluency disorder should be
      recognized as distinct from stuttering.

PMID- 27865229
TI  - A comparison of three strategies for reducing the public stigma associated with
      stuttering.
AB  - PURPOSE: The effects of three anti-stigma strategies for stuttering-contact
      (hearing personal stories from an individual who stutters), education (replacing
      myths about stuttering with facts), and protest (condemning negative attitudes
      toward people who stutter)-were examined on attitudes, emotions, and behavioral
      intentions toward people who stutter. METHOD: Two hundred and twelve adults
      recruited from a nationwide survey in the United States were randomly assigned to
      one of the three anti-stigma conditions or a control condition. Participants
      completed questionnaires about stereotypes, negative emotional reactions, social
      distance, discriminatory intentions, and empowerment regarding people who stutter
      prior to and after watching a video for the assigned condition, and reported
      their attitude changes about people who stutter. Some participants completed
      follow-up questionnaires on the same measures one week later. RESULTS: All three
      anti-stigma strategies were more effective than the control condition for
      reducing stereotypes, negative emotions, and discriminatory intentions from
      pretest to posttest. Education and protest effects for reducing negative
      stereotypes were maintained at one-week follow-up. Contact had the most positive
      effect for increasing affirming attitudes about people who stutter from pretest
      to posttest and pretest to follow-up. Participants in the contact and education
      groups, but not protest, self-reported significantly more positive attitude
      change about people who stutter as a result of watching the video compared to the
      control group. CONCLUSION: Advocates in the field of stuttering can use education
      and protest strategies to reduce negative attitudes about people who stutter, and
      people who stutter can increase affirming attitudes through interpersonal contact
      with others.

PMID- 27865230
TI  - Impact of social media and quality life of people who stutter.

PMID- 27865231
TI  - Long-term Consequences of Childhood Bullying in Adults who Stutter: Social
      Anxiety, Fear of Negative Evaluation, Self-esteem, and Satisfaction with Life.
AB  - PURPOSE: Psychosocial disorders have been reported in adults who stutter,
      especially social anxiety disorder. Social anxiety has been linked to childhood
      victimization. It is possible that recalled childhood victimization could be
      linked to psychosocial problems reported in some adults who stutter. METHOD:
      Participants were 36 adults who stutter and 36 adults who do not stutter (mean
      age=21.9 years). The Retrospective Bullying Questionnaire was completed for
      primary school, secondary school and university environments for physical,
      verbal, relational and cyber bullying. Participants were categorized into one of
      five groups (bully, victim, bully-victim, bystander and uninvolved) based ontheir
      responses. Participants completed four psychosocial scales: social interaction
      anxiety, fear of negative evaluation, self-esteem and satisfaction with life
      scales. RESULTS: The two groups differed with adults who stutter having higher
      social interaction anxiety, fear of negative evaluation and satisfaction with
      life. Analyses of variance revealed that victims had the highest scores among
      both groups on all four scales. CONCLUSION: Adults who recalled being victimized
      during childhood were more likely, regardless of whether they stutter or did not
      stutter, to have poorer psychosocial scale scores. These results show the
      lingering effects of childhood victimization, common in some children who
      stutter, may contribute to the reported psychosocial problems in adulthood. The
      need for early intervention for children who are bullied and future research with
      larger samples is warranted.

PMID- 27865232
TI  - Bedaquiline: Introducing a new drug to the MDR TB armamentarium.

PMID- 27865233
TI  - CYP2E1 polymorphism, acetylator profiles and drug-induced liver injury incidence
      of Indonesian tuberculosis patients.
AB  - OBJECTIVE: A polymorphism of CYP2E1 may be directly associated with the
      development of INH hepatotoxicity. We conducted this study to evaluate the
      association between polymorphisms of CYP2E1, Isoniazid (INH) concentration and
      the acetylator status of INH in cases of Indonesian tuberculosis patients with
      drug-induced liver disease (DILI). METHODS: We conducted our study with a cohort
      design consisting of 55 Indonesian adult tuberculosis (TB) patients. Acetylating
      phenotypes were studied in using the metabolic ratio of plasma AcHZ/HZ. DILI was
      defined using CTCAV version 4.0. The allelic and genotypic frequency
      distributions of CYP2E1 rs 3813867 were studied using the polymerase chain
      reaction - amplification refractory mutation system (ARMS) methodology. RESULTS:
      Patients with an INH concentration of more than 7MUg/mL showed a higher risk of
      developing DILI when compared with patients who showed a therapeutic range of 3
      6MUg/mL INH (OR: 1.3, 95% CI: 0.2-8.2). Slow acetylators had a higher incidence
      of DILI when compared with rapid acetylators (OR: 4.6, 95% CI: 1.3-15.9).
      Meanwhile, subjects with GC had a higher risk of DILI incidence (OR: 4.3, 95% CI:
      0.8-24.4). CONCLUSION: Our study shows that polymorphisms of CYP2E1 and slow
      acetylator may have role in the DILI incidence.

PMID- 27865234
TI  - Rapid detection of extensively drug-resistant (XDR-TB) strains from multidrug
      resistant tuberculosis (MDR-TB) cases isolated from smear-negative pulmonary
      samples in an Intermediate Reference Laboratory in India.
AB  - BACKGROUND: Direct sputum smear microscopy is commonly used for diagnosing
      tuberculosis (TB). The objectives of the study were first, to determine the
      recovery of Mycobacterium tuberculosis in smear-negative sputum samples through
      liquid culture (using MGIT 960) and solid culture (using LJ slant) and second, to
      screen multidrug-resistant isolates through line probe assay and further third,
      to identify XDR isolates through MGIT second-line DST from these positive MDR
      cultures in Delhi region. METHODS: In this study, the sample size was 717 (sputum
      smear AFB negative and culture positive for M. tuberculosis complex by both solid
      and liquid culture methods) MDRTB suspects who were enrolled from January 2014 to
      December 2014 at the Intermediate Reference Laboratory in New Delhi Tuberculosis
      Centre, New Delhi. Rapid line probe assay was performed on all culture-positive
      samples, which were direct smear-negative specimens, and LPA-confirmed MDR
      samples were tested on MGIT 960 second-line DST for identification of XDR
      strains. RESULTS: An overall increase in the culture positivity (9.4%) among
      these smear-negative cases shows a good sign of recovery from M. tuberculosis
      infection in these samples. 717 (9.4%) positive cultures (MGIT+LJ) were subjected
      to line probe assay. Out of these 717 cultures, 9 (1.2%) were confirmed as NTM,
      50 (7%) were MDR, 4 (0.6%) were mono-rifampicin resistant and 654 (91.2%)
      cultures were sensitive to both drugs Rif and Inh, respectively. Out of these 54
      (50 MDR +4 mono-RIF resistant) cultures as screened by LPA, 1 (1.8%) was XDR, 10
      (18.6%) were mono-ofloxacin resistant and 1 (1.8%) was mono-Kanamycin resistant.
      Sensitivity to both drugs KAN and OFX was seen in 42 (77.8%) cultures.
      CONCLUSIONS: Since the bacterial load in direct smear-negative suspected MDR
      samples is less, it is important to recover mycobacteria by rapid liquid culture
      method in such samples. Initial screening for MDRTB is to be done in such cases
      by performing rapid molecular genotypic drug susceptibility test such as LPA.
      Baseline second-line DST is also done to rule out the XDR cases among them for
      rapid and better management of XDRTB patients.

PMID- 27865235
TI  - Role of real-time PCR for detection of tuberculosis and drug resistance directly
      from clinical samples.
AB  - BACKGROUND: Only a few studies done earlier in India reveal the utility of real
      time PCR in detecting drug resistance in cases of pulmonary tuberculosis.
      OBJECTIVES: The study was carried out to standardise real-time PCR (Quantitative
      real-time PCR, qPCR) targeting 16s RNA for the rapid detection of tuberculosis
      and its drug resistance from suspected TB patients. MATERIALS AND METHODS: Sputum
      samples from 100 clinically suspected tuberculosis patients, after processing
      were subjected to microscopy, MGIT culture and qPCR. qPCR targeted 16sRNA for
      detecting Mycobacterium tuberculosis complex, KatG and rpoB genes for detection
      of resistance to isoniazid and rifampicin respectively. 1% proportionate method
      and Line probe assay (Hain Lifesciences, Nehren, Germany) were used to confirm
      the MDR isolates. RESULTS: The study showed positivity of microscopy, culture and
      qPCR for M. tuberculosis as 37%, 44% and 46% respectively. Sensitivity of 100%
      and specificity of 96.5% in the detection of M. tuberculosis was observed for
      qPCR in comparison to culture. MDRTB was detected in 14 cases whereas
      monoresistance to rifampicin and isoniazid was detected in 1 and 3 samples
      respectively. CONCLUSION: Real-time PCR targeting 16sRNA, KatG and rpoB is a
      sensitive, specific, rapid and reliable technique to detect pulmonary
      tuberculosis and its MDR status directly from the sputum samples.

PMID- 27865236
TI  - PCR targeting IS6110 in diagnosing tuberculosis in children in comparison to MGIT
      culture.
AB  - BACKGROUND: Diagnosis of tuberculosis (TB) in children is difficult in children
      especially in extrapulmonary tuberculosis (EPTB). This study was conducted to
      evaluate the use of polymerase chain reaction (PCR) targeting IS6110 in the
      diagnosis of TB in children with pulmonary TB and EPTB and also to compare its
      performance with MGIT 960 culture and conventional microscopy. METHODS: A total
      of 142 cases (50 pulmonary, 92 extrapulmonary) of suspected TB patients <15 years
      of age were included in the study. The clinical specimens obtained from these
      cases were subjected to Ziehl-Neelsen staining (ZN), MGIT 960 TB culture and PCR
      targeting insertion sequence IS6110. Sensitivity and specificity of PCR were
      calculated in pulmonary and extrapulmonary specimens. The results were compared
      to MGIT culture. RESULTS: PCR targeting IS6110 sequence had sensitivity of 69.01%
      in various clinical specimens which was significantly more than MGIT culture
      showing a sensitivity of 47.41% (p<0.05). Sensitivity of PCR IS6110 in
      extrapulmonary specimens was 65.21% which was lower than sensitivity in pulmonary
      specimens (76%) but was not statistically significant (p>0.05). CONCLUSIONS:
      Diagnostic efficacy of PCR IS6110 in pulmonary and extrapulmonary TB cases was
      similar. PCR using IS6110 primer had significantly better efficiency than MGIT
      culture in diagnosing TB in children.

PMID- 27865237
TI  - Smoked and smokeless tobacco use among pulmonary tuberculosis patients under
      RNTCP in urban Puducherry, India.
AB  - BACKGROUND: Smoking is associated with unfavourable treatment outcomes like
      failures and defaults among the TB patients. OBJECTIVES: To study the prevalence
      and pattern of tobacco use among the pulmonary tuberculosis (PTB) patients in
      urban Pondicherry and study the association of various socio-demographic
      variables with current smoked and smokeless tobacco users. METHODS: A cross
      sectional study was conducted among 235 PTB patients from 6 randomly selected
      urban PHCs of Pondicherry from Jan 2013 to March 2014. Fagerstrom Test for
      Nicotine Dependence was used. Chi-square test and multiple-logistic regression
      were done. RESULTS: Prevalence of smoking among the PTB patients at the time of
      TB diagnosis was 35.3%, whereas the same during the continuation phase (CP) was
      23.4%. Among 83 smokers at the time of diagnosis, 52 modified and 31 did not
      modify their smoking after TB diagnosis. Similarly, prevalence of smokeless
      tobacco use both at the time of TB diagnosis and during CP was 9.8%. Male and
      lower education level was associated with current smoking. Similarly, female and
      lower education level was associated with current smokeless tobacco use.
      CONCLUSIONS: One-third of PTB patients used smoked or smokeless tobacco during
      their CP. Health programme needs to concentrate on PTB patients who continue to
      use smoked or smokeless tobacco during their treatment; necessary interventions
      need to be planned.

PMID- 27865238
TI  - Tuberculosis prevalence and socio-economic differentials in the slums of four
      metropolitan cities of India.
AB  - AIM: To understand tuberculosis (TB) prevalence among the slum dwellers of
      metropolitan cities of India and the factors associated with TB prevalence.
      METHODS: National Family Health Survey-III data for four metropolitan cities
      namely, Delhi, Mumbai, Kolkata and Chennai was used for this study. RESULTS:
      Prevalence of TB is significantly (P=0.001) higher in the slums than non-slums of
      Mumbai, Chennai and Kolkata cities. As the living standard increases, TB
      prevalence decreases. Logistic regression analysis uncovers that lower standard
      of living is highly associated with TB followed by place of residence (slum or
      non-slum). CONCLUSION: Mumbai has the highest prevalence among the four cities
      studied herein. Living standards, place of residence and absence of windows and
      electricity in the households are the factors associated with TB prevalence.

PMID- 27865240
TI  - Prediction equations for spirometry in adults in western India.
AB  - BACKGROUND: Spirometry is an essential investigation in pulmonology. The
      predicted normal spirometry values depend on various physiological parameters.
      This study was conducted to collect updated information on pulmonary functions in
      normal adults from western India. MATERIAL AND METHODS: A prospective
      observational study was undertaken at a tertiary hospital in Mumbai enrolling
      healthy subjects, 18-75 years, with ethnic origin from western India. Spirometry
      measurements were carried out as per ATS/ERS-2005 guidelines using a non-heated
      Fleish Pneumotachograph spirometer. Data was analyzed using SPSS for Pearson's
      correlation analysis, multiple linear regressions and log transformations of
      variables to get the best prediction equations. RESULTS: 310 subjects (185 males,
      125 females) were included. Lung function values were higher in men as compared
      to women. In multivariate linear regression models, age and height were major
      predictor variables for all spirometry parameters. Addition of weight as a
      determinant variable did not make significant contribution to the models except
      for PEFR in males and F75 in females. Regression equations were established for
      FVC, FEV1, FEV1/FVC ratio, PEFR, F25-75, F50, and F75. The standard-error-of
      estimate was provided to enable computation of lower limits of normal for these
      parameters. CONCLUSION: We propose regression equations for spirometry variables
      developed using the current standards for adult West Indian population fulfilling
      the long-felt need for updated equations.

PMID- 27865239
TI  - Patterns of granulomatous responses in TB lymphadenitis and their correlation
      with treatment outcomes.
AB  - INTRODUCTION: Four patterns are noted in aspirates of TB lymphadenitis with or
      without concomitant HIV. They are granulomatous, necrotizing granulomatous,
      predominantly necrotizing and necrotizing suppurative designated pattern 1, 2, 3
      and 4, respectively. The present study attempted to correlate granulomatous
      patterns, Acid Fast Bacilli (AFB) density with treatment outcomes. MATERIALS AND
      METHODS: The MGG and Papanicolaou stained slides of 56 lymphadenitis patients, 38
      TB and 18 TB with seropositive HIV were studied for two years. The AFB were
      stratified into: 0 - nil (1 - <=1 AFB, 2 - >1 but <10 AFB, 3 - >=10 AFB)/10
      fields. RESULTS: There were 35 males and 21 females. Eleven aspirates
      demonstrated AFB. TB+HIV lymphadenitis displayed a higher AFB score. TB+HIV
      lymphadenitis aspirates significantly showed higher grade granulomas and AFB.
      TB+HIV lymphadenitis required >=8-month treatment. Granulomas (pattern 3 or 4)
      but not high AFB scores required longer treatment (>6 months). Treatment of AFB
      (>=1) often extended to >6 months. CONCLUSION: TB with seropositive HIV, possibly
      due to defective immune regulation exhibited granulomas (pattern 3 or 4)
      necessitating treatment for >=8 months. Pattern 3 or 4 granulomas irrespective of
      HIV status demanded >6-month treatment.

PMID- 27865241
TI  - Tobacco use and its impact on pulmonary health among elderly population in rural
      area of Muzaffarnagar - A cross-sectional study.
AB  - BACKGROUND: The tobacco use is significant in Indian rural population. Among
      them, elderly people in rural area are at special risk due to ageing and other
      factors. The impact of tobacco use on elderly health, therefore, needs to be
      studied in depth in rural context. OBJECTIVE: To study the patterns of tobacco
      use and its consequent impact on pulmonary health of the elderly. DESIGN AND
      METHODOLOGY: A community-based cross-sectional study was done (April 1st to
      September 30th, 2014) in the field practice area (village Bilaspur) of Rural
      Health Training Centre (RHTC) of Muzaffarnagar Medical College, Muzaffarnagar. A
      simple random sampling was used and elderly of 60 years and above were
      interviewed by semi-structured interview schedule. The data were analyzed by
      software Epi-info. version 7.1.3.3. RESULTS AND CONCLUSION: The prevalence of
      tobacco usage among elderly was 56.7%, in which smoking was the dominant one
      (37%) and majority being in the form of Bidi (56.7%). Tobacco usage was
      significantly associated not only with age, sex, and caste (p<0.05 each), but
      occupational and socio-economic status (p<0.01 each) also; however, literacy was
      the most significant factor (p<0.0001) among all. The tobacco usage in smoking
      form was highly significantly associated with the presence of chronic obstructive
      pulmonary disease (p<0.0001), elucidating a significant impact on their pulmonary
      health. The rural elderly people need health education regarding curtailing the
      use of tobacco for their better health from health clinics.

PMID- 27865242
TI  - A study on knowledge and awareness about tuberculosis in senior school children
      in Bangalore, India.
AB  - BACKGROUND: Tuberculosis (TB) is an infectious disease caused by Mycobacterium
      tuberculosis (M. tuberculosis), commonly affecting the lungs. All health care
      professionals including the pharmacists provide a valuable public health role in
      promoting community awareness of TB particularly in reducing stigma attached to
      TB. Thus, creating awareness at a community level could play a vital role in
      control and prevention of TB. OBJECTIVES: To determine whether educational
      intervention would affect the level of TB awareness among students of selected
      schools and pre-university colleges (PUCs) in Bangalore urban and Bangalore rural
      regions. METHODOLOGY: The present study was conducted among the students of 8th,
      9th, 10th and PUC in Bangalore rural and urban jurisdiction (n=2635). A
      questionnaire was designed in English and Kannada language, consisting of 20
      questions with multiple-choice answers. A 30-minute visual health education was
      given on TB in English, followed by general pictorial presentation, and the data
      were collected as pre-test and post-test. RESULTS: Data collected from 2635
      participants during pre- and post-education session revealed that mean score
      improved from 8.77+/-2.59 to 14.95+/-1.99. Impact of the education session showed
      a significant knowledge improvement about TB from 1.59% (pre-education) to 49.67%
      (post-education). CONCLUSION: The present study clearly demonstrated that a
      simple, 30-minute health education session did have a positive impact on
      knowledge and awareness about TB among school children as observed with increase
      in mean knowledge score from pre-test to post-test, indicating that empowerment
      of students could guide the community on various aspects of TB.

PMID- 27865243
TI  - Lessons learnt from active tuberculosis case finding in an urban slum setting of
      Agra city, India.
AB  - Active case finding (ACF) is recognized as one of the key strategies to reach the
      missing 3 million cases in high tuberculosis (TB) burden countries. In India, we
      conducted ACF as a pilot project to assess its operational feasibility in four
      slums of Agra city in 2012 and covered 3940 households (in 14 wards) with a
      population of 21,870. Trained community volunteers visited households with an
      intention to provide information on TB and refer those with cough >=2 weeks for
      sputum smear examination. Volunteers identified 8 persons with cough of >=2 weeks
      by asking the first or the main respondent of the household. However, by directly
      asking (or probing) all available members of the household, they identified 374
      persons with cough of >=2 weeks. All 382 persons with cough of >=2 weeks were
      referred for sputum smear examination. While 40% of those referred reached health
      facilities for sputum examination on their own, 60% had to be accompanied by the
      community volunteers to the health facility for sputum smear examination by Ziehl
      Neelsen staining method. Eventually, seven persons were found to be sputum smear
      positive. This study highlighted important aspects for implementing ACF: First,
      all household members have to be asked for TB symptoms and Second, mere referral
      for sputum examination is not enough and there is a need to support people to
      reach the health facility for sputum smear examination.

PMID- 27865244
TI  - Tubercular osteomyelitis of calcaneum bone: A rare occurrence.
AB  - In spite of the endemic nature of tuberculosis in India, skeletal tuberculosis is
      relatively infrequent. Involvement of foot bones is uncommon and isolated
      calcaneum is even rarer. Osteoarticular tuberculosis is a diagnostic enigma, as
      the characteristic signs and symptoms of this disease may be absent, or mimic
      other disorders, leading to emergence of complications and therapeutic delay,
      particularly when the disease affects unusual sites. Here, we are reporting the
      case of 20-year-old male, who presented with a rare localization of tubercular
      osteomyelitis involving the calcaneum without adjacent joint involvement to draw
      attention to this exceptional location in adults, managed with anti-tubercular
      treatment and gained excellent recovery.

PMID- 27865245
TI  - Adolescent with recurrent tuberculosis: Can it be chronic granulomatous disease?
AB  - Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency
      disorder with recurrent bacterial and fungal infections like Staphylococcus
      aureus, Nocardia spp, Serratia marcescens, Burkholderia cepacia, Salmonella spp.
      and Aspergillus species. We present a 13-year-old male child who had 3 episodes
      of tuberculosis (TB) at 5 years, 8 years and 13 years of age, respectively, with
      no other intercurrent infections and who was diagnosed as CGD at the age of 13
      years. This case highlights the possibility of phenotypic variations of CGD. The
      diagnosis of CGD should also be sought in all children with recurrent TB.

PMID- 27865246
TI  - Renal tuberculosis presenting as acute pyelonephritis - A rarity.
AB  - One of the major health problems faced particularly by the developing world since
      ages is that of tuberculosis (TB). Genito-urinary tuberculosis (GUTB) is the
      second most common extrapulmonary TB, with kidney being the most frequent site of
      infection. Due to the diverse and atypical clinical manifestations of urinary TB,
      the disease is easy to misdiagnose. The diagnosis of renal TB should be suspected
      in a nonspecific bacterial cystitis associated with a therapeutic failure or a
      sterile pyuria and a past history of pulmonary TB with important radiologic
      findings, particularly with the help of CT scan. Here, we describe a case of
      renal TB where no clinical or radiological features suggestive of renal TB were
      present. The diagnosis was only evident after the histopathological examination
      of the excised kidney. This case highlights the importance of suspecting renal TB
      as an important cause of kidney disease, which can lead to irreversible renal
      function loss particularly in an endemic area, and also the diversity that this
      disease may acquire in its presentation leading to misdiagnosis. In such a case,
      particularly in a high endemic area for TB, therapeutic trial of ATT may also be
      considered to avoid unnecessary surgical intervention and end-stage renal
      disease.

PMID- 27865247
TI  - Implementing a central venous catheter self-management education program for
      patients with cancer.
AB  - PURPOSE: To evaluate the effects of the central venous catheter self-management
      education program (CVC S-MEP) in improving knowledge, attitude, and behavior
      regarding CVC and in decreasing CVC-related complications in patients with cancer
      during homecare service. METHODS: A quasi-experimental, sequential cohort design
      study of patients with cancer and who have CVCs was performed to compare the
      effect of CVC S-MEP with usual care. RESULTS: The study group consisted of 45
      participants (26 male and 19 female), and the mean age was 46.1 (SD, 10.5) years.
      The subjects of the CVC S-MEP had significantly high mean levels of self
      management knowledge (p = 0.007), attitude (p < 0.001), and behavior (p = 0.002).
      Also, the participants in the CVC S-MEP had significantly lower frequency of
      catheter-related complications (p = 0.030). CONCLUSIONS: The CVC S-MEP helped
      improve patients' ability to resolve problems and adequately respond to CVC
      related emergency situations by fostering greater self-care ability.
      Additionally, providing practical information for CVC self-management in a
      gradual and repetitive manner had a notable positive effect on patients.

PMID- 27865248
TI  - The Chinese version of hospital anxiety and depression scale: Psychometric
      properties in Chinese cancer patients and their family caregivers.
AB  - PURPOSE: The Hospital Anxiety and Depression Scale (HADS) acts as one of the most
      frequently used self-reported measures in cancer practice. The evidence for
      construct validity of HADS, however, remains inconclusive. The objective of this
      study is to evaluate the psychometric properties of the Chinese version HADS (C
      HADS) in terms of construct validity, internal consistency reliability, and
      concurrent validity in dyads of Chinese cancer patients and their family
      caregivers. METHODS: This was a cross-sectional study, conducted in multiple
      centers: one hospital in each of the seven different administrative regions in
      China from October 2014 to May 2015. A total of 641 dyads, consisting of cancer
      patients and family caregivers, completed a survey assessing their demographic
      and background information, anxiety and depression using C-HADS, and quality of
      life (QOL) using Chinese version SF-12. Data analysis methods included
      descriptive statistics, confirmatory factor analysis (CFA), and Pearson
      correlations. RESULTS: Both the two-factor and one-factor models offered the best
      and adequate fit to the data in cancer patients and family caregivers
      respectively. The comparison of the two-factor and single-factor models supports
      the basic assumption of two-factor construct of C-HADS. The overall and two
      subscales of C-HADS in both cancer patients and family caregivers had good
      internal consistency and acceptable concurrent validity. CONCLUSIONS: The Chinese
      version of the HADS may be a reliable and valid screening tool, as indicated by
      its original two-factor structure. The finding supports the basic assumption of
      two-factor construct of HADS.

PMID- 27865249
TI  - Development and validation of the preparedness for Colorectal Cancer Surgery
      Questionnaire: PCSQ-pre 24.
AB  - PURPOSE: The aims of the study were to develop and psychometrically evaluate a
      patient-reported outcome instrument for the measurement of preoperative
      preparedness in patients undergoing surgery for colorectal cancer. METHODS: This
      study was conducted in two stages: a) instrument development (item generation,
      construction of items and domains), empirical verification and b) instrument
      evaluation. A questionnaire with 28 items measuring preparedness for surgery was
      developed covering four domains and was tested for content validity with an
      expert panel and with patients. Psychometric testing of the questionnaire was
      conducted on 240 patients undergoing elective surgery for colorectal cancer.
      RESULTS: The scale content validity index of the preparedness items was 0.97. The
      final version consisted of 24 items measuring 4 subscales: Searching for and
      making use of information, Understanding and involvement in the care process,
      Making sense of the recovery process and Support and access to medical care.
      Confirmatory factor analysis revealed good model fit with standardized factor
      loadings ranging from 0.58 to 0.97. A well-fitting second-order factor model
      provided support for a total preparedness score with second-order factor loadings
      ranging from 0.75 to 0.93. The ordinal alpha values of the four latent factors
      ranged from 0.92 to 0.96, indicating good internal consistency. The polyserial
      correlations with the total score were 0.64 (p < 0.01) for the overall
      preparedness question and 0.37 (p < 0.01) for overall well-being. CONCLUSION: The
      Swedish Preparedness for Colorectal Cancer Surgery Questionnaire for use in the
      preoperative phase demonstrated good psychometric properties based on a sound
      conceptualization of preparedness.

PMID- 27865250
TI  - Are children as relatives our responsibility? - How nurses perceive their role in
      caring for children as relatives of seriously ill patients.
AB  - PURPOSE: The purpose of this study was to elucidate how nurses perceive their
      role in caring for children as relatives to a parent with a serious physical
      illness. METHOD: A qualitative explorative design with focus group interviews was
      used. In total, 22 nurses working at one neurological, one haematological and two
      oncological wards were interviewed. The transcripts from the interviews were
      analysed in steps in accordance with inductive qualitative content analysis.
      RESULTS: This study revealed six variations in how nurses perceived their role in
      the encounter with child relatives, ranging from being convinced that it is not
      their responsibility to being aware of the children's situation and working
      systematically to support them. CONCLUSION: Nurses should consider whether their
      patients have children who might be affected by their parent's illness. The
      nurses' self-confidence when meeting these children must be increased by
      education in order to strengthen their professional role. Furthermore, guidelines
      on how to encounter child relatives are required.

PMID- 27865251
TI  - Like being covered in a wet and dark blanket - Parents' lived experiences of
      losing a child to cancer.
AB  - PURPOSE: The aim of this study was to illuminate parents' lived experiences of
      losing a child to cancer. METHOD: Interviews and a narrative about parents'
      experiences of losing a child to cancer were gathered from six parents of
      children whom had participated in a longitudinal study across the child's illness
      trajectory. The analysis of the data was inspired by van Manen's hermeneutic
      phenomenological approach. RESULTS: One essential theme emerged: Like being
      covered in a wet and dark blanket, as well as six related themes: Feeling
      conflicting emotions, Preparing for the moment of death, Continuing parenting
      after death, Recollecting and sharing memories, Working through the sorrow and
      New perspectives in life. CONCLUSION: There is a need for good palliative care.
      If not, there is a risk that the parent will perseverate and blame themselves for
      not being a good parent during the suffering child's last time in life. Meetings
      with the parents six months and two years after the child's death might
      facilitate healing through the grief process.

PMID- 27865252
TI  - Measuring trust in nurses - Psychometric properties of the Trust in Nurses Scale
      in four countries.
AB  - PURPOSE: The purpose of this study was to examine psychometric properties of
      three translated versions of the Trust in Nurses Scale (TNS) and cancer patients'
      perceptions of trust in nurses in a sample of cancer patients from four European
      countries. METHODS: A cross-sectional, cross-cultural, multi-site survey design
      was used. The data were collected with the Trust in Nurses Scale from patients
      with different types of malignancies in 17 units within five clinical sites (n =
      599) between 09/2012 and 06/2014. Data were analyzed using descriptive and
      inferential statistics, multivariate methods and psychometrics using exploratory
      factor analysis, Cronbach's alpha coefficients, item analysis and Rasch analysis.
      RESULTS: The psychometric properties of the data were consistent in all
      countries. Within the exploratory factor analysis the principal component
      analysis supported the one component structure (unidimensionality) of the TNS.
      The internal consistency reliability was acceptable. The Rasch analysis supported
      the unidimensionality of the TNS cross-culturally. All items of the TNS
      demonstrated acceptable goodness-of-fit to the Rasch model. Cancer patients
      trusted nurses to a great extent although between-country differences were found.
      CONCLUSIONS: The Trust in Nurses Scale proved to be a valid and reliable tool for
      measuring patients' trust in nurses in oncological settings in international
      contexts.

PMID- 27865253
TI  - Perceptions of patients, families, physicians and nurses regarding challenges in
      cancer disclosure: A descriptive qualitative study.
AB  - PURPOSE: The findings of numerous studies have illustrated that there is still a
      high proportion of cancer patients in Eastern and Middle-East countries including
      Iran, who are not properly informed of their disease due to the concealment
      atmosphere which still prevails. This descriptive qualitative study is aimed at
      exploring perceptions of patients, patients' family members, physicians and
      nurses regarding cancer disclosure challenges. METHODS: Thirty-five participants
      (15 patients, 6 family members, 9 physicians, and 5 nurses) were selected through
      purposive sampling. The data were collected through in-depth interviews; after
      which they were analyzed using a qualitative content analysis with an inductive
      approach. RESULTS: Data analysis revealed the following three categories: first,
      challenges related to healthcare system which deals with the deficiencies,
      strains and concerns in medical setting and healthcare team training; second,
      challenges related to family insistence on concealment which includes their fear
      of cancer disclosure and its negative impact on the patients; and third,
      challenges related to policy making which consists of deficiencies in legislative
      and supportive institutions for advocacy of truth telling. CONCLUSIONS:
      Successful move from concealment to effective disclosure attitude in cancer
      patients in Iran requires a national determination for resolving challenges in
      medical education as well as other different social, cultural and policy making
      dimensions.

PMID- 27865255
TI  - Recommendations for symptom management in women with vulvar neoplasms after
      surgical treatment: An evidence-based guideline.
AB  - PURPOSE: To develop an evidence-based guideline for nurses and other health care
      professionals involved in pre- and postsurgical care of women with vulvar cancer
      (VC) or vulvar intraepithelial neoplasia (VIN). METHODS: This evidence-based
      guideline was developed according to six domains of the methodological framework
      AGREE II. Literature research with focus on cancer care, symptom management and
      self-management/counselling was conducted from April to August 2013 in the
      databases CINAHL, Cochrane Library, PsycINFO, PubMed as well as in 14
      international guideline databases. Interdisciplinary experts (n = 14) were
      involved in the development of the guideline from December 2013 to January 2014.
      This guideline is currently tested in the WOMAN-PRO II RCT (Clinical Trial No:
      NCT01986725). RESULTS: For the definition of recommendations, five guidelines,
      one meta-analysis, two systematic reviews and two randomized controlled trials
      were included. In total, 24 recommendations were formulated to answer 22 clinical
      questions based on patients' perspective and experts' opinion. Evidence ranged
      from 3.5 to 5 (3.5 = weak evidence and/or clinical relevance, 5 = best evidence
      and/or clinical relevance). The recommendations were subsumed under different
      themes regarding physical, psychological and psychosocial aspects. CONCLUSIONS:
      The clinical practice guideline developed in this study firstly provides
      recommendations for symptom management issues focusing on self-management
      interventions for women with VC or VIN. As an interdisciplinary guideline it
      should be used in addition to the existing medical guideline in the German
      speaking context.

PMID- 27865254
TI  - A systematic literature review comparing the psychological care needs of patients
      with mesothelioma and advanced lung cancer.
AB  - PURPOSE: Psychological distress which adversely affects a person's experience of
      cancer has been shown to be highly prevalent in patients with mesothelioma.
      Historically, the assumption has been made that the evidence guiding the
      supportive care needs for lung cancer is relevant to those with mesothelioma. The
      objective of the study was to evaluate if the psychological care needs differ
      between patients with pleural mesothelioma and those with advanced lung cancer.
      METHODS: A search of MEDLINE, CINAHL, PsycARTICLES, Psychology and Behavioural
      Sciences Collection, PsycINFO databases, grey literature and the Cochrane Library
      of Systematic Reviews identified 17 studies meeting a predefined inclusion
      criteria. These were critically appraised for quality. Data relating to
      psychological experiences was extracted which was then synthesised narratively
      and through a process of meta ethnography. RESULTS: Common themes identified
      across the studies created 10 key concepts. These were uncertainty, normality,
      hope/hopelessness, stigma/blame/guilt, family/carer concern, physical symptoms,
      experience of diagnosis, iatrogenic distress, financial/legal and death and
      dying. Key similarities and differences were identified between the mesothelioma
      and lung cancer evidence. CONCLUSIONS: There is limited research exploring the
      lived experiences of those with mesothelioma and lung cancer, with the majority
      of them having methodological and/or reporting concerns compromising the
      conclusions made. However, reoccurring themes in the evidence were found
      suggesting a number of areas where the psychological experience of mesothelioma
      differs from that of advanced lung cancer. These findings warrant further
      research to explore further and if proven, the need for the provision of
      specialist mesothelioma care services is affirmed.

PMID- 27865256
TI  - Opioid-taking self-efficacy as influencing emotional status in patients with
      cancer pain.
AB  - PURPOSE: The purpose of this study was to evaluate how much of the variance in
      emotional status amongst Taiwanese cancer patients could be accounted for by
      opioid-taking self-efficacy. METHODS: This cross-sectional study included 109
      cancer patients who had taken prescribed opioid analgesics for cancer related
      pain in the past week and completed the Opioid-Taking Self-Efficacy Scale-CA
      (OTSES-CA) and Hospital Anxiety and Depression Scale. RESULTS: There was a
      significant and negative correlation between scores on anxiety and self-efficacy
      total scale (r = -0.29, p < 0.01), self-efficacy communication subscale (r = 
      0.37, p < 0.01), self-efficacy acquiring help subscale (r = -0.22, p < 0.05) and
      self-efficacy managing treatment related concerns subscale (r = -0.32, p < 0.01).
      However, the correlation between scores on depression and the self-efficacy total
      scale was not significant (r = -0.18, p > 0.05); only the self-efficacy
      communication subscale was significantly and negatively associated with
      depression (r = -0.27, p < 0.01). The opioid-taking self-efficacy total scale
      accounted for 8% of predicting the patients' anxiety. Opioid-taking self-efficacy
      subscales accounted for 20% (R2 = 0.20, p = 0.000) of the variance in predicting
      anxiety and 10% (R2 = 0.10, p = 0.02) of the variance in predicting depression.
      CONCLUSIONS: This study highlights the potential importance of a patient's opioid
      taking self-efficacy beliefs in their emotional status, which is relevant to
      cancer pain.

PMID- 27865257
TI  - Pain and social processes for hospice cancer patients: An integrative review.
AB  - PURPOSE: Hospice cancer patients experience poorly-controlled pain in spite of
      widely-disseminated evidence-based guidelines for use by hospice care
      practitioners. Pain management occurs in the context of the interdisciplinary
      team, centered on a caring triad in the home: the person with pain, their
      caregiver, and their nurse. This review: 1) Summarizes what is known about
      differing ways that members of the hospice caring triad (patients, caregivers,
      and nurses) interpret and respond to cancer pain, in order to develop a cancer
      pain social processes theoretical framework, 2) Identifies gaps in understanding
      of hospice cancer pain social processes, and 3) Identifies framework concepts for
      research-based clinical practice with potential to improve pain outcomes.
      METHODS: Our integrative review of the literature resulted in the identification
      and synthesis of 21 unique studies of cancer pain social processes, which were
      categorized according to a social processes framework and hospice caring triad
      member roles, using a social processes concepts matrix. RESULTS: Pain meanings,
      goals, and related responses vary for persons with pain, caregivers, and nurses.
      Studies have explored individual social processes concepts or triad member roles.
      Studies identify the need for pain meaning to be included in hospice pain
      management plans. CONCLUSIONS: To our knowledge, no single study has generated a
      framework for hospice cancer pain social processes addressing and incorporating
      the roles of all three caring triad members. Therefore, comprehensive hospice
      cancer pain clinical evaluation and interventions plans may be missing key
      elements of pain management, especially for persons with ongoing poorly
      controlled pain.

PMID- 27865258
TI  - Preparing young people for future decision-making about cancer risk in families
      affected or at risk from hereditary breast cancer: A qualitative interview study.
AB  - PURPOSE: Women carrying the mutated BRCA gene, have approximately an 80% life
      time risk of developing breast cancer with 50% risk of their children inheriting
      the gene mutation. Many parents find it difficult to know when and how to
      disclose this information to their children and how such disclosure might affect
      their child's future decision-making. METHOD: This study explored the
      communication of genetic risk information in families using qualitative semi
      structured interviews conducted with parents, children (7-11years) and young
      people (12-18years) affected or at risk from a BRCA gene mutation. Thematic
      analysis was applied to coded transcripts producing four themes; family
      communication, perception of cancer risks, risk management strategies and impact
      of genetic risk communication in children and young people's decision making.
      RESULTS: Twenty-seven individuals from 11 families took part, recruited through
      purposive sampling techniques. Cancer risk caused by a BRCA gene mutation induced
      a sense of fear in parents about their children's future. As a result, parents
      with hereditary breast cancer disclosed limited information about the risks
      associated with prophylactic surgery and/or the psychological and emotional
      impacts of surgery on body image. This had implications to children and young
      people's perceptions of prophylactic procedures, which were already influenced by
      cultural understandings of the 'desirable body' and increasing acceptance and
      proliferation cosmetic surgery. CONCLUSION: Lack of risk management information
      and the acculturation of cosmetic surgery combined to limit children and young
      people's understanding of the impact of hereditary breast cancer; reducing their
      ability to actualise the physiological, psychological and emotional consequences
      of surgery.

PMID- 27865259
TI  - Web based survivorship interventions for women with breast cancer: An integrative
      review.
AB  - PURPOSE: Breast cancer survivors' experience a range of negative sequelae post
      treatment including depression, anxiety, physical side effects from treatment,
      sexuality concerns and decreased quality of life. Survivorship care is
      recommended by the IOM to meet the post treatment needs of survivors but
      implementation is variable and barriers to delivery such as time and resource
      restraints have been identified. Web-based interventions may be a way to overcome
      some barriers to providing quality survivorship care that is efficacious, cost
      efficient and convenient. The purpose of this integrative review is to summarize
      and synthesize the current research on web-based interventions for breast cancer
      survivorship care and evaluate the data to determine potential implications for
      practice. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines were used to guide this integrative review. Key
      search terms included breast cancer, survivor, intervention, web, internet and
      technology. Articles evaluating web-based survivorship interventions (n = 405)
      for early stage breast cancer patients who completed active therapy were
      included. RESULTS: Fifteen studies met inclusion criteria: six randomized
      controlled trials, six survey based studies, one qualitative study, one
      retrospective chart review and one mixed methods study. Studies evaluating
      cognitive behavioral therapy provided the strongest data. Other studies evaluated
      exercise and lifestyle interventions, symptom management programs and
      pilot/exploratory work. Findings suggest that web-based survivorship
      interventions are feasible and acceptable to breast cancer survivors.
      CONCLUSIONS: Web-based survivorship interventions have the potential to meet the
      needs of breast cancer survivors while possibly overcoming some of the documented
      barriers to survivorship care implementation.

PMID- 27865260
TI  - Antimicrobial resistance and molecular characterization of virulence genes,
      phylogenetic groups of Escherichia coli isolated from diarrheic and healthy camel
      calves in Tunisia.
AB  - This study was conducted to determine the prevalence of virulence genes,
      serogroups, antimicrobial resistance and phylogenetic groups of Escherichia coli
      strains isolated from diarrheic and healthy camel calves in Tunisia. From 120
      fecal samples (62 healthy and 58 diarrheic camel calves aged less than 3 months),
      70 E. coli isolates (53 from diarrheic herds and 17 from healthy herds) were
      examined by PCR for detection of the virulence genes associated with pathogenic
      E. coli in animals. A significantly greater frequency of the f17 gene was
      observed in individual camels and in herds with diarrhea, this gene being found
      in 44.7% and 41.5% of isolates from camels and herds with diarrhea versus 22.5%
      and 11.7% in camels (p=0.05) and herds without diarrhea (p=0.02). The aida,
      cnf1/2, f18, stx2 and paa genes were found only in isolates from camels with
      diarrhea, although at a low prevalence, 1.8%, 3.7%, 1.8%, 3.7% and 11.3%,
      respectively. Prevalence of afa8, cdtB, eae, east1, iroN, iss, kpsMTII, paa, sfa,
      tsh and papC genes did not differ significantly between herds with or without
      diarrhea. Genes coding for faeG, fanC, f41, estI, estII, CS31a and eltA were not
      detected in any isolates. All isolates were sensitive to amikacin,
      chloramphenicol, ciprofloxacin, gentamicin and ceftiofur and the highest
      frequency of resistance was observed to tetracycline, and ampicillin (52.8% and
      37.1% respectively). The phylogenetic groups were identified by conventional
      triplex PCR. Results showed that E. coli strains segregated mainly in
      phylogenetic group B1, 52.8% in diarrheic herds and 52.9% in healthy herds.

PMID- 27865261
TI  - Humanized mice in infectious diseases.
AB  - The pathogenesis of infectious agents with human tropism can only be properly
      studied in an in vivo model featuring human cells or tissue. Humanized mice
      represent a small animal model featuring human cells or tissue that can be
      infected by human-specific viruses, bacteria, and parasites and also providing a
      functional human immune system. This makes the analysis of a human immune
      response to infection possible and allows for preclinical testing of new vaccines
      and therapeutic agents. Results of various studies using humanized mice to
      investigate pathogens with human tropism are presented in this review. In
      addition, the limitations of humanized mice and methods to improve this valuable
      animal model are discussed.

PMID- 27865262
TI  - Soluble forms of CD46 are detected in Bos taurus plasma and neutralize BVDV, the
      bovine pestivirus.
AB  - The pestivirus bovine viral diarrhea virus (BVDV) is known to bind to the CD46
      molecule, which subsequently promotes entry of the virus. Mapping of the BVD
      virion-binding site has shown that two peptides, 66EQIV69 and 82GQVLAL87, located
      on antiparallel beta sheets in the most distal complement control protein module
      (CCP1), provide the attachment platform. In the present study, we reveal new CD46
      encoding transcripts that are predicted to encode CCP1-containing soluble forms.
      Further, we show that the serum of most adult cattle contains soluble CD46
      (sCD46) and that a recombinant soluble isoform neutralizes BVDV infectivity in an
      in vitro assay. We have then established an ELISA for determination of plasma
      sCD46 in a large cohort of animals. Overall, serum sCD46 amounts to 8+/-18ng/mL
      (mean+/-SD, n=440), with a IC [95-105] ranging from 6,4 to 9,8ng/mL and extreme
      values between 0 and 178ng/mL. We found that sCD46 is not detectable in fetal and
      neonatal sera and that its plasma concentration increases progressively up to
      adulthood. We also detected high- and low-sCD46 performers and show that this
      phenotype does not depend of environment. As modern rearing techniques make it
      possible to disseminate genetically-determined phenotypes very quickly in a
      population, a large-scale study examining whether high-sCD46 animals provide
      epidemiological protection against BVDV infection and transmission should be
      undertaken.

PMID- 27865263
TI  - Molecular assessment of the transplacental transmission of Toxoplasma gondii,
      Neospora caninum, Brucella canis and Ehrlichia canis in dogs.
AB  - Given the fact that numerous microbial species can be detected in pregnant female
      dogs, the objective of this study was to assess the transplacental transmission
      of Brucella canis, Ehrlichia canis, Neospora caninum and Toxoplasma gondii in
      stillborn puppies. This study involved 41 stillborn puppies, 78.6% of which were
      positive for T. gondii, 52.4% for N. caninum and 59.5% for B. canis. E. canis was
      not detected in any of the analyzed puppies. Pregnancy is an important
      physiological condition for the transmission of infectious agents to puppies and
      transplacental transmission may be epidemiologically relevant in the spread of
      these opportunistic agents.

PMID- 27865264
TI  - Changes in serum biomarkers of oxidative stress after treatment for canine
      leishmaniosis in sick dogs.
AB  - Canine leishmaniosis (CanL) is a zoonotic disease being endemic in several parts
      of the world. In this study we investigated the behavior of a panel of biomarkers
      of oxidative stress in 12 sick dogs naturally infected by CanL before and at days
      30 and 180 of a successful therapy with a standard treatment. The assays total
      oxidant status (TOS), trolox equivalent antioxidant capacity (TEAC), ferric
      reducing ability of plasma (FRAP), cupric reducing antioxidant capacity (CUPRAC),
      serum thiol and paraoxonase 1 (PON1) were included in the panel. In addition,
      correlations between biomarkers of oxidative stress and inflammation (C-reactive
      protein (CRP) and ferritin) and urinary protein:creatinine ratio (UPC) were
      calculated. Serum CUPRAC, thiol and PON1 significantly increased after treatment
      and were negatively correlated with CRP, ferritin and UPC. This study
      demonstrates that biomarkers of oxidative stress, not previously studied in
      leishmaniosis such as CUPRAC and thiol, can change after a successful treatment
      for CanL showing a potential for use in monitoring the treatment of this disease.

PMID- 27865266
TI  - Ability of an oral formulation of afoxolaner to protect dogs from Borrelia
      burgdorferi infection transmitted by wild Ixodes scapularis ticks.
AB  - A randomized, blinded, negative controlled study was conducted to determine
      whether treatment with afoxolaner (NexGard(r), Merial, Inc.) would prevent the
      transmission of Borrelia burgdorferi to dogs by wild caught Ixodes scapularis
      ticks. Twenty healthy dogs were randomly assigned to two groups of ten dogs each.
      Ten dogs were treated orally on Day 0 at a dose near the minimum recommended dose
      of afoxolaner of 2.5mg/kg (actual doses 2.5-3.1mg/kg) and ten control dogs were
      not treated. On Day 28, each dog was infested with approximately 50 adult unfed
      wild caught I. scapularis that had a 67% B. burgdorferi infection rate
      (determined by polymerase chain reaction). On Day 33, live ticks were counted and
      removed. No ticks were found on treated dogs while control dogs had an average of
      21.4 ticks. To detect infection, the B. burgdorferi-specific C6 antibody SNAP(r)
      4Dx(r) test (IDEXX) was performed on serum collected before infestation (all dogs
      seronegative on Days -6 and 27) and on Days 48, 63, 77 and 92. The ten treated
      dogs remained seronegative through the end of the study (Day 92), while nine out
      of the ten control dogs were infected, as demonstrated by their seroconversion to
      being positive for the presence of the B. burgdorferi-specific C6 antibody
      starting on Day 48. In this study, all dogs treated with NexGard(r) 28days prior
      to challenge with wild caught I. scapularis ticks were protected from B.
      burgdorferi infection, while nine out of the ten untreated control dogs were
      infected.

PMID- 27865265
TI  - Monitoring of West Nile virus, Usutu virus and Meaban virus in waterfowl used as
      decoys and wild raptors in southern Spain.
AB  - In the last decade, the number of emerging flaviviruses described worldwide has
      increased considerably, with wild birds acting as the main reservoir hosts of
      these viruses. We carried out an epidemiological survey to determine the
      seroprevalence of antigenically related flaviviruses, particularly West Nile
      virus (WNV), Usutu virus (USUV) and Meaban virus (MBV), in waterfowl used as
      decoys and wild raptors in Andalusia (southern Spain), the region considered to
      have the highest risk of flaviviruses circulation in Spain. The overall
      flaviviruses seroprevalence according to bELISA was 13.0% in both in decoys
      (n=1052) and wild raptors (n=123). Specific antibodies against WNV, USUV and MBV
      were confirmed by micro virus neutralization tests in 12, 38 and 4 of the
      seropositive decoys, respectively. This is the first study on WNV and USUV
      infections in decoys and the first report of MBV infections in waterfowl and
      raptors. Moreover we report the first description of WNV infections in short-toed
      snake eagle (Circaetus gallicus) and Montagu's harrier (Circus pygargus). The
      seropositivity obtained indicates widespread but not homogeneous distribution of
      WNV and USUV in Andalusia. The results also confirm endemic circulation of WNV,
      USUV and MBV in both decoys and wild raptors in southern Spain. Our results
      highlight the need to implement surveillance and control programs not only for
      WNV but also for other related flaviviruses. Further research is needed to
      determine the eco-epidemiological role that waterfowl and wild raptors play in
      the transmission of emerging flaviviruses, especially in decoys, given their
      close interactions with humans.

PMID- 27865268
TI  - Epitope mapping of Campylobacter jejuni flagellar capping protein (FliD) by
      chicken (Gallus gallus domesticus) sera.
AB  - Campylobacter jejuni, a Gram-negative rod, is a zoonotic pathogen associated with
      human acute bacterial gastroenteritis worldwide. The flagellum, composed of more
      than 35 proteins, is responsible for colonization of C. jejuni in the host
      gastrointestinal tract as well as inducing protective antibodies against the
      homologous serotype. In our previous study, we demonstrated that the flagellar
      capping protein (FliD) is an immunodominant protein that reacted strongly to sera
      from field chickens. In this communication, we mapped linear immunoreactive
      epitopes on FliD using a set of 158 synthetic peptides of 15-mer overlapping with
      11 amino acid residues on peptide microarrays with sera from field chickens. The
      results from peptide microarrays showed (1) no cross-reactivity of the
      immobilized peptides with the secondary anti-chicken antibody in the control
      incubation, and (2) heterogeneous patterns of sera reacting to the immobilized
      peptides. The peptides that reacted to more than three chicken sera and had
      higher averages of fluorescence units were selected for further validation by the
      peptide ELISA. The results showed peptides 24, 91 and 92 had relatively high
      reactivity and less variation among 64 individual serum samples, indicating these
      peptides represented the shared immunodominant epitopes on the C. jejuni FliD
      protein. These peptides were also recognized by sera from chickens immunized with
      the purified recombinant FliD protein. The findings of the specific shared linear
      immunodominant epitopes on FliD in this study provide a rationale for further
      evaluation to determine their utility as epitope vaccines covering multiple
      serotypes for chicken immunization, and subsequently, for providing safer poultry
      products for human consumption.

PMID- 27865269
TI  - The immunopathogenesis of staphylococcal skin infections - A review.
AB  - Staphylococcus aureus and S. pseudintermedius are the major causes of bacterial
      skin disease in humans and dogs. These organisms can exist as commensals on the
      skin, but they can also cause severe or even devastating infections. The immune
      system has evolved mechanisms to deal with pathogenic microorganisms and has
      strategies to combat bacteria of this type. What emerges is a delicate "peace"
      between the opposing sides, but this balance can be disrupted leading to a full
      blown "war". In the ferocious battle that ensues, both sides attempt to get the
      upper hand, using strategies that are comparable to those used by modern day
      armies. In this review article, the complex interactions between the immune
      system and the organisms are described using such military analogies. The process
      is described in a sequential manner, starting with the invasion itself, and
      progressing to the eventual battlezone in which there are heavy casualties on
      both sides. By the end, the appearance of a simple pustule on the skin surface
      will take on a whole new meaning.

PMID- 27865267
TI  - Occurrence of Pseudocowpox virus associated to Bovine viral diarrhea virus-1,
      Brazilian Amazon.
AB  - In 2011, an outbreak of severe vesicular disease occurred in the state of Para,
      Amazon region. Besides proliferative or verrucous lesions, cattle showed atypical
      clinical signs such as diarrhea and leading to death. The animals were submitted
      to clinical, pathological and molecular diagnosis, and laboratory tests have
      confirmed the presence of Pseudocowpox virus (PCPV), a Parapoxvirus genus member,
      and have also found Bovine viral diarrhea virus-1 (BVDV-1), probably causing
      persistent infection. The results of molecular diagnostics, followed by
      sequencing data demonstrated the circulation of both viruses (PCPV and BVDV-1) in
      an area previously affected by another poxvirus, as Vaccinia virus.The
      cocirculation between PCPV and BVDV-1 indicates a major concern for animal health
      because the clinical presentation can be a severe disease. This is the first
      detection of PCPV in the Brazilian Amazon.

PMID- 27865271
TI  - Bacterial contamination of eggs and behaviour of poultry flocks in the free range
      environment.
AB  - The free range production system is becoming more common in Australia and is
      expected to increase. Free range hens are exposed to more stressors in comparison
      to hens from barn and cage systems and it is suggested that stress can increase
      bacterial shedding on eggs. The aims of this study were to examine the level of
      total bacteria and Enterobacteriaceae populations, as well as the presence of
      Salmonella and Campylobacter, in eggs collected from two free range flocks on two
      different farms and to conduct longitudinal observations of the behaviour and
      welfare of hens in the free range production system. Hen age (weeks) was shown to
      have a significant effect (increase) on the level of total bacteria on the egg
      shell surface and in shell pores, as well as having an effect on feather
      condition score. As the hens aged, the frequency of external visual egg
      characteristics increased, as did feather condition score (where feather
      condition was poorer). These observations indicate areas which should be
      investigated further to improve the food safety of eggs and optimise the welfare
      of free range hens.

PMID- 27865270
TI  - Serum apolipoprotein-A1 as a possible biomarker for monitoring treatment of
      canine leishmaniosis.
AB  - The aims of this study were: the identification of proteins differentially
      represented in the serum proteome of dogs with leishmaniosis after treatment and
      the verification of one selected protein as a possible biomarker for treatment
      monitoring. Serum samples from five dogs with leishmaniosis, before and after
      treatment were pooled into two groups and analysed using 2-dimensional
      electrophoresis followed by mass spectrometry analysis (MS). The MS analysis
      allowed the identification of 8 proteins differently expressed. APO-A1 was
      selected and an immunoturbidimetric assay was validated for its measurement in
      dogs. Significantly decreased concentrations of APO-A1 in dogs with leishmaniosis
      and a significant increase after a good response to the treatment were observed,
      suggesting that APO-A1 could be a potential biomarker of treatment monitoring
      with the advantages of an automated measurement.

PMID- 27865273
TI  - Genetics of Pancreatic Cancer and Its Implications on Therapy.
AB  - Over the past decade, emerging technologies have provided new insights into the
      genomic landscape of pancreatic ductal adenocarcinoma (PDA). In addition to the
      commonly recognized genetic drivers of pancreatic carcinogenesis (KRAS, CDKN2A,
      TP53, SMAD4), new genes and pathways have been implicated. However, these efforts
      have not identified any new high-frequency actionable mutations, limiting the
      success of mutation-targeted therapy in PDA. This article provides a report on
      the current landscape of pancreas cancer genetics and targeted therapeutics.

PMID- 27865272
TI  - Proline-arginine rich (PR-39) cathelicidin: Structure, expression and functional
      implication in intestinal health.
AB  - Proline-Arginine-39 (PR-39) is a small cationic, proline and arginine rich,
      cathelicidin that plays an important role in the porcine innate immune system.
      Although PR-39 was first discovered in intestinal cell lysates of pigs,
      subsequent research has indicated that it is primarily expressed in bone marrow
      and other lymphoid tissues including the thymus and spleen, as well as in
      leukocytes. Mature PR-39 cathelicidin has anti-microbial activity against many
      gram-negative and some gram-positive bacteria. PR-39 is also a bridge between the
      innate and adaptive immune system with recognized immunomodulatory, wound
      healing, anti-apoptotic, and pro-angiogenic functions. The purpose of this review
      is to summarize our current knowledge about the structure, expression, and
      functions of PR-39 and its potential to promote intestinal homeostasis. This
      understanding is relevant in the search of alternative therapeutics against
      diarrheic enterocolitis, a major problem faced by pork producers both in terms of
      costs and risk of zoonosis.

PMID- 27865275
TI  - Imaging Evaluation of Pancreatic Cancer.
AB  - Imaging studies are critical for the detection, characterization, initial
      staging, management, and monitoring of pancreatic cancer cases. Treatment of
      pancreatic cancer requires a multidisciplinary approach. Ideally, assessing
      resectablility with imaging and subsequent treatment decisions should be made at
      a high-volume center of excellence with a multidisciplinary team. This article
      reviews the major imaging modalities used to evaluate pancreatic neoplasms, with
      an emphasis on pancreatic imaging protocols. The imaging appearance of solid
      pancreatic neoplasms and the imaging criteria used to stage and determine
      resectability for pancreatic ductal adenocarcinoma are described. An approach to
      standardized radiologic reporting is also reviewed.

PMID- 27865276
TI  - Endoscopic Evaluation in the Workup of Pancreatic Cancer.
AB  - Early diagnosis and accurate staging of pancreatic cancer is very important to
      plan optimal management strategy. Endoscopy plays an important role in the
      diagnosis and management of pancreatic cancer. Endoscopic ultrasound imaging
      (EUS) is the most sensitive modality for diagnosis, especially for small
      pancreatic tumors; it also allows tissue acquisition for histological diagnosis.
      Computed tomography scanning and EUS play complementary roles in staging and are
      comparable in determining resectability. Endoscopic retrograde
      cholangiopancreatography allows tissue sampling but is limited to palliative
      biliary drainage in most cases. In this article, we review the role of endoscopy
      in the diagnosis and management of pancreatic adenocarcinoma, with special
      emphasis on the use of endoscopic ultrasound and endoscopic retrograde
      cholangiopancreatography (ERCP).

PMID- 27865274
TI  - Screening for Pancreatic Cancer.
AB  - Pancreatic cancer (PC) is a highly fatal disease that can only be cured by
      complete surgical resection. However, most patients with PC have unresectable
      disease at the time of diagnosis, highlighting the need to detect PC and its
      precursor lesions earlier in asymptomatic patients. Screening is not cost
      effective for population-based screening of PC. Individuals with genetic risk
      factors for PC based on family history or known PC-associated genetic syndromes,
      however, can be a potential target for PC screening programs. This article
      provides an overview of the epidemiology and genetic background of familial PC
      and discusses diagnostic and management approaches.

PMID- 27865277
TI  - Surgical Therapy for Pancreatic and Periampullary Cancer.
AB  - Surgery is the key component of treatment for pancreatic and periampullary
      cancers. Pancreatectomy is complex, and there are numerous perioperative and
      intraoperative factors that are important for achieving optimal outcomes. This
      article focuses specifically on key aspects of the surgical management of
      periampullary and pancreatic cancers.

PMID- 27865278
TI  - Adjuvant and Neoadjuvant Therapy for Resectable Pancreatic and Periampullary
      Cancer.
AB  - Pancreatic adenocarcinoma is a relatively uncommon malignancy associated with a
      high rate of cancer-related mortality despite best efforts to perform curative
      surgery. Adjuvant therapy in patients after surgical resection is associated with
      improved overall survival. Adjuvant treatment approaches may include either
      chemotherapy alone or a combination of chemotherapy and radiation therapy.
      Neoadjuvant approaches, also including either chemotherapy alone or a combination
      of chemotherapy and radiation therapy, are under investigation. Periampullary
      cancers constitute a rare and heterogeneous group of tumors that are typically
      treated as pancreatic cancers given their histologic similarities and tumor
      location.

PMID- 27865279
TI  - Enhanced Recovery Pathways in Pancreatic Surgery.
AB  - Enhanced recovery after surgery (ERAS) protocols were first introduced to help
      recovery after colorectal surgery. They have now been applied to multiple
      surgical specialties, including pancreatic surgery. ERAS protocols in pancreatic
      surgery have been shown to decrease length of stay and possibly postoperative
      morbidity.

PMID- 27865280
TI  - Postpancreatectomy Complications and Management.
AB  - Although mortality rates after pancreatectomy have decreased, the incidence of
      postoperative morbidity remains high. The major procedure-related complications
      are pancreatic fistula, delayed gastric emptying, and postpancreatectomy
      hemorrhage. The International Study Group of Pancreatic Surgery defined leading
      complications in a standardized fashion, allowing unbiased comparison of
      operative results and management strategies. Risk factors for postoperative
      complications have been investigated and quantitative scoring systems established
      to estimate patient-specific risks. Management of postpancreatectomy
      complications has shifted from an operative to a conservative approach.
      Nevertheless, postoperative morbidities may have a profound impact on patient
      recovery and length of hospital stay and are associated with increased hospital
      costs.

PMID- 27865281
TI  - Definition and Management of Borderline Resectable Pancreatic Cancer.
AB  - Patients with localized pancreatic ductal adenocarcinoma seek potentially
      curative treatment, but this group represents a spectrum of disease. Patients
      with borderline resectable primary tumors are a unique subset whose successful
      therapy requires a care team with expertise in medical care, imaging, surgery,
      medical oncology, and radiation oncology. This team must identify patients with
      borderline tumors then carefully prescribe and execute a combined treatment
      strategy with the highest possibility of cure. This article addresses the issues
      of clinical evaluation, imaging techniques, and criteria, as well as
      multidisciplinary treatment of patients with borderline resectable pancreatic
      ductal adenocarcinoma.

PMID- 27865282
TI  - Techniques of Vascular Resection and Reconstruction in Pancreatic Cancer.
AB  - Multimodality therapy has become the standard approach for the treatment of
      pancreatic cancer. With improved response rates to newer chemotherapeutic agents,
      tumors that used to be considered unresectable are now being considered for
      operation. Neoadjuvant therapy for borderline resectable pancreatic cancer is
      considered standard of care and venous resection/reconstruction is no longer
      controversial. Arterial resection and reconstruction in select patients has also
      proven to be safe when done in highly specialized centers by high-volume
      surgeons. This article reviews indications for, and technical aspects of,
      vascular resection/reconstruction and shunting procedures during pancreatectomy,
      including critical elements of perioperative care.

PMID- 27865283
TI  - Management of Locally Advanced Pancreatic Cancer.
AB  - The diagnosis for locally advanced pancreatic cancer is based on high-quality
      cross-sectional imaging, which shows tumor invasion into the celiac/superior
      mesenteric arteries and/or superior mesenteric/portal venous system that is not
      reconstructable. The optimal management of these patients is evolving quickly
      with the advent of newer chemotherapeutics, radiation, and nonthermal ablation
      modalities. This article presents the current status of initial chemotherapy,
      surgical therapy, ablative therapy, and radiation therapy for patients with
      nonmetastatic locally advanced unresectable pancreatic cancer. Surgical resection
      offers the best chance of long-term disease control and the only chance for cure
      for patients with nonmetastatic exocrine pancreatic cancer.

PMID- 27865284
TI  - Management of Metastatic Pancreatic Adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal and clinically
      challenging malignancies to treat, with an estimated 5-year survival rate of
      approximately 7%. At the time of initial presentation, a majority of patients
      have metastatic disease. The median overall survival in these patients with good
      performance status is 8.5 to 11.1 months and in patients with significantly
      impaired performance status, even less. Strategies to integrate novel agents with
      traditional cytotoxic therapies are under investigation and hold promise for
      improving outcomes in patients with metastatic PDAC. This article focuses on the
      current management options and novel therapeutics for metastatic PDAC.

PMID- 27865286
TI  - Intraductal Papillary Mucinous Neoplasm of the Pancreas.
AB  - The incidence of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas
      has been rising in the past 2 decades, driven mainly by the widespread use of
      cross-sectional imaging. IPMNs are intraductal mucin-producing neoplasms that
      involve the main pancreatic duct or its side branches and lack the ovarian stroma
      typically seen in mucinous cystic neoplasms. The International Association of
      Pancreatology released consensus guidelines in 2006 and 2012 providing clinical
      algorithms based on IPMN features and risk of malignancy. In this article, we
      review the different classifications of IPMNs, their natural history, and
      clinical management and address recent controversies in the literature.

PMID- 27865285
TI  - Palliative Care for Pancreatic and Periampullary Cancer.
AB  - Most patients with pancreatic cancer will present with metastatic or locally
      advanced disease. Unfortunately, most patients with localized disease will
      experience recurrence even after multimodality therapy. As such, pancreatic
      cancer patients arrive at a common endpoint where decisions pertaining to
      palliative care come to the forefront. This article summarizes surgical,
      endoscopic, and other palliative techniques for relief of obstructive jaundice,
      relief of duodenal or gastric outlet obstruction, and relief of pain due to
      invasion of the celiac plexus. It also introduces the utility of the palliative
      care triangle in clarifying a patient's and family's goals to guide decision
      making.

PMID- 27865287
TI  - Surgical Management of Pancreatic Neuroendocrine Tumors.
AB  - Pancreatic neuroendocrine tumors (PNETs) are a rare, heterogeneous group of
      neoplasms infamous for their endocrinopathies. Up to 90% of PNETs, however, are
      nonfunctional and are frequently detected incidentally on axial imaging during
      the evaluation of vague abdominal symptoms. Surgery remains the mainstay of
      therapy for patients diagnosed with both functional and nonfunctional PNETs.
      However, the multifaceted nature of PNETs challenges treatment decision making.
      In general, resection is recommended for patients with acceptable perioperative
      risk and amenable lesions.

PMID- 27865288
TI  - Foreword.

PMID- 27865289
TI  - Preface.

PMID- 27865290
TI  - Pneumatic Dilation of the Lower Esophageal Sphincter Can Now Be Successfully
      Performed Without Morbidity.
AB  - BACKGROUND: Patients with dysphagia may be diagnosed with impaired lower
      esophageal sphincter (LES) relaxation and treated with pneumatic dilation (PD),
      stretching and tearing LES muscle fibers. Esophageal perforation has been
      reported to be as high as 10%. We conducted a retrospective study to evaluate the
      perforation rate of PD when used for impaired relaxation of the LES using current
      techniques. METHODS: A chart review was conducted to identify patients referred
      for esophageal manometry by high-resolution manometry and later received PD from
      January 2013 to April 2016. The diagnoses of achalasia, gastroesophageal junction
      outlet obstruction or hypertensive LES with accompanying impaired LES relaxation
      were based on the Chicago Classification III. Demographic data, clinical
      findings, treatment approaches and outcomes were explored. RESULTS: A total of
      187 patients were referred for dysphagia and had esophageal manometry during this
      time frame. In all, 62 patients (34 female), mean age of 52 years, met the
      criteria for incomplete relaxation of the LES and underwent a total of 88 PD
      procedures. All initial PD procedures used the 30-mm diameter balloon, 18
      subsequently required a 35-mm balloon and 8 went on to 40-mm balloon size. No
      perforations or other complications were documented by
      esophagogastroduodenoscopy, gastrografin testing immediately postdilation or by
      subsequent clinical outcome. CONCLUSIONS: PD by an experienced gastroenterologist
      using general anesthesia, fluoroscopic guidance, Rigiflex balloon equipment and a
      specific repetitive technique can be successfully performed without perforation.
      Hence, the already known therapeutic efficacy of PD can now be combined with the
      knowledge that there is essentially no accompanying perforation rate.

PMID- 27865291
TI  - Adiposity and Cardiovascular Risk Factor Variables in Childhood Are Associated
      With Premature Death From Coronary Heart Disease in Adults: The Bogalusa Heart
      Study.
AB  - BACKGROUND: More than 600 deaths of all causes have been documented over the 40
      year duration of the Bogalusa Heart Study. Of these, 97 deaths have been related
      to cardiovascular events, based on obituaries published in local newspapers,
      death certificates obtained from the State Health Department, information from
      the coroner and word of mouth by nursing staff from the community. METHODS: This
      study was a retrospective longitudinal cohort with several observations of each
      subject. It consisted of 6 cross-sectional surveys of children aged 5-7 years,
      conducted between 1973 and 1988, and 4 cross-sectional surveys of previously
      examined subjects as young adults extending into middle age, conducted between
      1988 and 2010. RESULTS: Excluding pulmonary, congenital and noncoronary
      cardiovascular diseases, 46 deaths (average age at death = 44.7 years, range: 31
      55) were considered to have been related to coronary artery disease, that is,
      myocardial infarction. Cardiovascular risk factor observations, gathered from
      multiple surveys (average of 4.4 surveys, range: 1-14) since childhood, indicated
      that body fatness and elevated blood pressure beginning in childhood were more
      common in subjects who later died of coronary artery disease than in living
      subjects. CONCLUSIONS: The present findings emphasize that sub-clinical
      cardiovascular disease begins early in life and that early prevention is vital.

PMID- 27865292
TI  - Katrina's Legacy: Processes for Patient Disaster Preparation Have Improved but
      Important Gaps Remain.
AB  - BACKGROUND: Ensuring continuity of care for patients with chronic illness, who
      are elderly or indigent presents unique challenges after disasters; this
      population has fewer financial resources, is less likely to evacuate, has limited
      access to recovery resources and is significantly dependent on charitable and
      government-funded institutions for care. This study expands a previous
      investigation of the extent to which healthcare providers in coastal Mississippi
      and Alabama have made changes to facilitate continued care to these populations
      after disasters. METHODS: Key informants representing healthcare and social
      services organizations serving health-disparate residents of the Mississippi and
      Alabama Gulf Coast were interviewed regarding disaster preparation planning for
      the period of 2009-2012. Interview transcripts were qualitatively coded and
      analyzed for emerging themes using ATLAS.ti software. RESULTS: Participant
      organizations have implemented changes to ensure continuity of care for patients
      with chronic illness in case of disasters. Changes include patient assistance
      with predisaster preparation and training; evacuation planning and assistance;
      support to find resources in evacuation destinations; equipping patients with
      prescription information, diagnoses, treatment plans and advance medications when
      a disaster is imminent; multiple methods for patients to communicate with
      providers and more mandated medical needs shelters. Patients whose chronic
      conditions were diagnosed post-Katrina are more likely to underestimate the need
      to prepare. Further, patients' lack of compliance tends to increase as time
      passes from disasters. CONCLUSIONS: Although changes were implemented, results
      indicate that these may be inadequate to completely address patient needs. Thus,
      additional efforts may be needed, underscoring the complexity of adequate
      disaster preparation among disparate populations.

PMID- 27865293
TI  - Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: Transcoronary and
      Endocardial Approach.
AB  - Septal reduction therapy is the gold standard treatment method for symptomatic,
      hypertrophic obstructive cardiomyopathy. Although surgical myectomy is a well
      established and effective technique with decades of experience in its
      application, use of transcoronary alcohol septal ablation has increased
      precipitously owing to the less-invasive nature of the procedure. Moreover,
      endocardial septal ablation therapy is a relatively newly defined modality, and
      outcomes of the procedure are not clearly elucidated yet. In this review, we
      aimed to present nonsurgical septal reduction approaches in patients with
      hypertrophic obstructive cardiomyopathy.

PMID- 27865294
TI  - Overuse and Misperceptions of Nonsteroidal Anti-inflammatory Drugs in the United
      States.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most
      commonly used medications worldwide. The availability of hundreds of products
      containing an NSAID, combined with a lack of recognition and understanding of
      NSAIDs, can increase the potential of consumers to inadvertently exceed the
      recommended NSAID dosage, which can cause potentially serious side effects.
      Physician and consumer education regarding the appropriate use of NSAIDs can help
      prevent NSAID misuse. Evaluations of current consumer patterns of NSAID use and
      perceptions about NSAIDs are necessary to develop targeted educational programs.
      MATERIALS AND METHODS: An online and telephone survey of 1,750 U.S. adults was
      conducted to obtain information about the patterns of use and perceptions about
      prescription and over-the-counter NSAIDs and medicines. The survey was compared
      to similar surveys conducted in 1997, 2001 and 2002. RESULTS: NSAIDs are widely
      used, with 63% of respondents reporting use within the past 12 months. NSAIDs
      were not well recognized by generic or brand names and many respondents were
      unaware or unconcerned about potential side effects. NSAID misuse was common,
      with 19% using more than the recommended dose and 24% using multiple NSAIDs
      concomitantly. NSAID use appears to have increased since 2002 but the level of
      NSAID awareness and pattern of NSAID misuse has not changed. CONCLUSIONS: NSAIDs
      are widely used and often used in a manner that increases the risk of serious
      side effects. Sufficient knowledge and understanding of NSAIDs is lacking and
      educational interventions directed to consumers and physicians are needed.

PMID- 27865295
TI  - Serum Pepsinogen Levels Are Correlated With Age, Sex and the Level of
      Helicobacter pylori Infection in Healthy Individuals.
AB  - BACKGROUND: To explore the relationship between age, sex, the level of
      Helicobacter pylori (HP) infection and serum pepsinogen (PG) in healthy people
      undergoing a medical examination. METHODS: A total of 6,596 "healthy" individuals
      undergoing a medical examination were selected as subjects in this study. The
      concentrations of serum pepsinogen I (PGI) and serum pepsinogen II (PGII) were
      tested for each of the subjects using time-resolved fluorescence immunoassay
      characterized with high sensitivity and wide measuring range. The infection ratio
      and level of HP were tested using a 13C-urea breath test to analyze the
      relationship between age, sex, HP infection, and serum PGs. RESULTS: The PGI,
      PGII and PGI-to-PGII ratio (x-+/-S) were higher in males than in females. The
      serum PGI and PGII levels gradually increased with age. HP infection rate was
      48.83%, and the serum PGI, PGII and PGI-to-PGII ratio (x-+/-S) were 187.05 +/-
      73.50ug/L, 18.09 +/- 8.68ug/L and 11.67 +/- 5.44, respectively in the HP-positive
      group and 150.39 +/- 67.04ug/L, 11.50 +/- 7.45ug/L and 15.67 +/- 8.19,
      respectively in the HP-negative group. There was significant difference in the
      detection rate of an abnormal PG between the 2 groups as with the worsening of HP
      infection, 13C-urea breath test and serum PGI and PGII levels increased, but the
      PGI-to-PGII ratio decreased significantly. CONCLUSIONS: Serum PGI and PGII levels
      were correlated with age, sex and the level of HP infection. Therefore, the
      influencing factors of age, sex and the level of HP infection should be
      considered when screening stomach diseases using PG.

PMID- 27865296
TI  - Cardiovascular Disease Risk Associated With the Long-term Use of Depot
      Medroxyprogesterone Acetate.
AB  - BACKGROUND: Depot medroxyprogesterone acetate (DMPA) contraception is widely used
      all over the world; however, it may lead to a decrease in high-density
      lipoproteins and an increase in low-density lipoproteins (LDL) and triglycerides.
      These changes in lipid profile have a direct effect on cardiovascular disease
      risk. This study has been conducted to investigate the relationship between DMPA
      use and lipid profile, and the effect of worsening of lipid profile on fasting
      blood glucose. The objective of the present study is to ascertain the effects of
      DMPA on lipid profiles and Castelli indices, and to estimate the risk of
      cardiovascular disease in the women using progesterone-only methods for
      contraception. METHODS: This was a multicenter case-control study including
      females of reproductive age. A total of 893 women were selected according to
      inclusion and exclusion criteria described below with the age range of 19-49
      years. Among these, 477 were females who were beginning DMPA for contraception
      whereas 416 were the matched controls of same age and socioeconomic status. The
      lipid profiles, Castelli indices and fasting blood sugar were evaluated before
      initiation of DMPA and thereafter at 3, 6, 9 and 12 months. Controls were also
      analyzed for the same parameters in the same manner as that of treated group. The
      results were analyzed by repeated measure analysis of variance followed by
      Tukey's post hoc test for the multiple comparisons. RESULTS: The results showed
      statistically significant differences in all parameters of lipid profile, namely
      cholesterol (180.7 +/- 38.8 versus 133.03 +/- 14.8mg/dL, and P = 0.000), LDL
      (120.04 +/- 36.2 versus 94.27 +/- 19.6mg/dL, and P = 0.000), very low-density
      lipoprotein cholesterol (24.6 +/- 10.0 versus 20.99 +/- 8.66mg/dL, and P =
      0.000), high-density lipoprotein (39.67 +/- 3.6 versus 44.13 +/- 4.22mg/dL, and P
      = 0.000), total cholesterol (713.05 +/- 110.2 versus 569.19 +/- 80.4mg/dL, and P
      = 0.000), triglycerides (126.33 +/- 48.8 versus 99.03 +/- 30.6mg/dL, and P =
      0.000), Castelli index I (4.61 +/- 1.2 versus 3.02 +/- 0.31, and P = 0.000) and
      Castelli index II (3.08 +/- 1.07 versus 2.13 +/- 0.41, and P = 0.000) between
      treated and control groups, respectively. Serum glucose levels were significantly
      higher (P <= 0.001) among the cases of DMPA (84.6394 +/- 7.425mg/dL) compared
      with that in the control (77.822 +/- 7.733mg/dL). CONCLUSIONS: This study clearly
      revealed that there is an increase in all deleterious lipid parameters and a
      decrease in favorable lipid measures. Hence, it can be concluded that continued
      use of DMPA may predispose females to the risk of cardiovascular disease in the
      long run.

PMID- 27865297
TI  - Cancer Screening 2016.
AB  - The primary goal of cancer screening is to reduce cancer-related mortality
      without incurring significant harm. Screening efforts for solid tumors,
      therefore, have targeted the precursors of the most common and the most deadly
      cancers-breast, cervical, colorectal, lung and prostate cancer. Balancing risk
      and benefit has led to controversy regarding the timing of cancer screening-when
      to begin, how often to screen and when to stop-and the nature of the modality of
      cancer screening-invasive or noninvasive, laboratory-centered or imaging
      centered. Evidence-based guidelines published by general medical societies,
      subspecialty societies and publicly funded task forces on population-based
      screening aid healthcare providers in making individualized decisions with their
      patients.

PMID- 27865298
TI  - The Value of Thromboelastography for Bleeding Risk Prediction in Hematologic
      Diseases.
AB  - BACKGROUND: This study aimed to explore the correlations between
      thromboelastography (TEG) parameters with platelet (PLT) count and fibrinogen and
      to evaluate the value of the maximal amplitude (MA) for bleeding risk prediction.
      METHODS: A total of 1,559 patients with hematologic diseases underwent PLT
      counting and TEG tests, and 1,201 of these patients underwent conventional
      coagulation tests. Patients were divided into a bleeding group and a nonbleeding
      group according to their clinical records. RESULTS: Patients in the bleeding
      group had lower PLT counts, alpha-angle values, MA values and higher K values
      (all P < 0.05) than patients in the nonbleeding group. Low PLT counts (<=30 *
      109/L) were found in 265 patients and bleeding episodes occurred in 109 patients
      (41.13%). A total of 99 patients had both low MA values and bleeding episodes in
      this subgroup. A total of 124 of the 265 patients (46.79%) had hematological
      malignancies. In the 2 different types of diseases, there was a similar tendency
      in bleeding risk prediction according to the receiver operating characteristic
      curves. The curves using both the PLT counts and MA values show a higher
      sensitivity and a slightly lower specificity than those of the PLT count or MA
      alone. CONCLUSIONS: There are some correlations between the TEG parameters and
      the traditional hemostatic parameters. The combination of the PLT counts and MA
      values had greater predictive value for bleeding risk in hematological diseases
      when the PLT counts were at a low level (<=30 * 109/L).

PMID- 27865301
TI  - Resveratrol Inhibited Non-small Cell Lung Cancer Through Inhibiting STAT-3
      Signaling.
AB  - BACKGROUND: Resveratrol has demonstrated many beneficial effects against cancers;
      however, the mechanism remains unclear. Non-small cell lung cancer accounts for
      80% of lung cancers. The present study was designed to observe the effects and
      related mechanisms of resveratrol on non-small cell lung cancer in in vitro A549
      cells. MATERIALS AND METHODS: The anticancer effects of resveratrol were analyzed
      on cell viability, migration and invasion, proliferation and apoptosis. Cell
      viability was determined by sulphorhodamine B assays. Cell proliferation and
      apoptosis were determined by flow cytometry and migration and invasion by
      transwell chamber analysis. Expression of STAT-3 was examined by real-time
      polymerase chain reaction and western blot. Overexpressing vector of STAT-3 was
      also constructed and transfected into A549 cells to observe the effects of
      resveratrol on STAT-3 signaling. RESULTS: The results showed that resveratrol
      displayed a dose-dependent and time-dependent cytotoxicity action on A549 cell
      viability. Resveratrol also inhibited proliferation, migration and invasion and
      promoted apoptosis in a time-dependent manner from 0-72 hours. Further study
      showed that resveratrol inhibited the messenger RNA and protein expression of
      STAT-3, and overexpressed STAT-3 abolished the effects of resveratrol on
      proliferation, apoptosis, migration and invasion totally or in part. CONCLUSIONS:
      These results suggest that the anticancer effects of resveratrol are mediated by
      STAT-3 signaling.

PMID- 27865302
TI  - Improving Resident Teaching Through Clinical Case Conference Presentations in
      Japan.

PMID- 27865303
TI  - A Tear in the Heart: Myocardial Laceration Following Left Ventriculogram With a
      Dedicated Radial Catheter.

PMID- 27865304
TI  - Brain Natriuretic Peptide Counteracting the Renin-angiotensin-aldosterone System
      in Accelerated Malignant Hypertension.
AB  - We describe 2 patients, a 52-year-old woman and a 57-year-old man, with rapidly
      progressive hypertension and marked elevation of brain natriuretic peptide who
      exhibited polyuria, natriuresis, hypokalemia, posterior reversible encephalopathy
      syndrome and left ventricular dysfunction together with retinopathy and
      nephropathy, which were attenuated in a short time span of 1-2 months with
      normalization of blood pressure after the antihypertensive treatment. The
      possible role of brain natriuretic peptide in the pathophysiology of accelerated
      malignant hypertension was discussed and a review of the literature was
      completed.

PMID- 27865300
TI  - Effect of Dapagliflozin Treatment on Fluid and Electrolyte Balance in Diabetic
      Rats.
AB  - AIM: This study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on
      fluid or electrolyte balance and its effect on urea transporter-A1 (UT-A1),
      aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in
      diabetic rats. METHODS: Diabetes mellitus (DM) was induced by injection of
      streptozotocin into the tail vein. Serum Na+, K+, Cl- concentration, urine Na+,
      K+, Cl- excretion, blood glucose, urine glucose excretion, urine volume, urine
      osmolality and urine urea excretion were analyzed after the administration of
      dapagliflozin. UT-A1, AQP2 and NKCC2 proteins were detected by western blot.
      RESULTS: Dapagliflozin treatment decreased blood glucose concentration by 38% at
      day 7 and by 47% at day 14 and increased the urinary glucose excretion rate
      compared with the untreated diabetic animals. Increased 24-hour urine volume,
      decreased urine osmolality and hyponatremia, hypokalemia and hypochloremia
      observed in diabetic rats were attenuated by dapagliflozin treatment. Western
      blot analysis showed that UT-A1, AQP2 and NKCC2 proteins are upregulated in DM
      rats over control rats; dapagliflozin treatment results in a further increase in
      inner medulla tip UT-A1 protein abundance by 42% at day 7 and by 46% at day 14,
      but it did not affect the DM-induced upregulation of AQP2 and NKCC2 proteins.
      CONCLUSION: Dapagliflozin treatment augmented the compensatory changes in
      medullary transport proteins in DM. These changes would tend to conserve solute
      and water even with persistent glycosuria. Therefore, diabetic rats treated with
      dapagliflozin have a mild osmotic diuresis compared to nondiabetic animals, but
      this does not result in an electrolyte disorder or significant volume depletion.

PMID- 27865299
TI  - Targeting the Mammalian Target of Rapamycin in Lung Cancer.
AB  - Lung cancer is the leading cause of cancer death worldwide. Despite advances in
      its prevention and management, the prognosis of patients with lung cancer remains
      poor. Therefore, much attention is being given to factors that contribute to the
      development of this disease, the mechanisms that drive oncogenesis and tumor
      progression and the search for novel targets that could lead to the development
      of more effective treatments. One cellular pathway implicated in lung cancer
      development and progression is that of the mammalian target of rapamycin. Studies
      involving human tissues have linked lung cancer with abnormalities in this
      pathway. Furthermore, studies in vitro and in vivo using animal models of lung
      cancer reveal that targeting this pathway might represent an effective means of
      treating this disease. As a result, there is significant effort invested in the
      development of drugs targeting mammalian target of rapamycin and related pathways
      in the clinical setting.

PMID- 27865305
TI  - Persistent Pruritic Lesions in Adult-onset Still's Disease.

PMID- 27865306
TI  - Nocardia Bacteremia and Endocarditis in a Patient With a Sulfa Allergy.

PMID- 27865307
TI  - Erratum to "Blood Volume Measurement as a Tool in Diagnosing Syncope" [Am J Med
      Sci 334 (2007) 53-56].

PMID- 27865308
TI  - Chronic Suppurative Otitis Media Complicated With Mastoiditis: An Unusual
      Presentation of Tuberculosis.

PMID- 27865309
TI  - Erdheim-Chester Disease Presenting With Intractable Exophthalmos and Bone
      Lesions.

PMID- 27865310
TI  - The Diabetic Charcot Foot from 1936 to 2016: Eighty Years Later and Still
      Growing.
AB  - Knowledge of diabetic Charcot neuroarthropathy (DCN) has grown tremendously since
      this condition was first described in 1936 by William Riely Jordan. Despite
      advancements in diagnostic approaches and treatment options making DCN limb
      salvage a more viable option, ongoing and additional research is needed to
      determine the definitive pathogenesis, which may aid in prevention of the
      condition. This article chronicles the main developments for the study and
      management of DCN since 1936 and recommends using the term diabetic Charcot
      Jordan foot when specifically managing foot and ankle neuroarthropathy joints in
      patients with diabetic neuropathy.

PMID- 27865311
TI  - Conservative and Pharmacologic Treatments for the Diabetic Charcot Foot.
AB  - Charcot neuroarthropathy is a disabling complication of diabetic neuropathy.
      Prolonged immobilization in a total contact cast (TCC) is among the main
      treatments. Education of health care professionals in the application of TCC
      together with well-conducted clinical trials are required to overcome its
      frequent underuse. There are no established pharmacologic therapies to treat this
      condition; however, there is an overwhelming need for a new therapeutic approach.
      Novel targeted drug delivery systems are required to prevent the pathologic bone
      and joint destruction of the Charcot neuroarthropathy and this may lead to an
      improved outcome in diabetic patients with this condition.

PMID- 27865312
TI  - An Overview of Internal and External Fixation Methods for the Diabetic Charcot
      Foot and Ankle.
AB  - Diabetic Charcot neuroarthropathy (DCN) of the foot and ankle is a challenging
      disease with regard to clinical presentation, pathogenesis, and prognosis. Its
      surgical management is equally difficult to interpret based on the wide array of
      options available. In the presence of an ulceration or concomitant osteomyelitis,
      internal fixation by means of screws, plates, or intramedullary nailing needs to
      be avoided when feasible. External fixation becomes a great surgical tool when
      managing DCN with concomitant osteomyelitis. This article describes internal and
      external fixation methods along with available literature to enlighten surgeons
      faced with treating this complex condition.

PMID- 27865313
TI  - Surgical Equinus Correction for the Diabetic Charcot Foot: What the Evidence
      Reveals.
AB  - Triceps surae contracture, or equinus, is a known deforming force in the foot and
      ankle. Biomechanical studies have shown that ankle equinus significantly alters
      gait and plantar pressures, and in the diabetic neuropathic patient population,
      this can propagate plantar ulceration and/or Charcot neuroarthropathy (CN).
      Surgical correction of equinus is globally and frequently used to aid in plantar
      wound healing in the neuropathic diabetic patient, with and without CN. Treatment
      guidelines for equinus correction in this medically complex population are
      undefined and lack evidence from high-quality published peer-reviewed studies.

PMID- 27865314
TI  - Surgical Treatment Options for the Diabetic Charcot Midfoot Deformity.
AB  - Management of diabetic Charcot midfoot deformity is one of the most demanding
      aspects of foot and ankle surgery. Its treatment should aim at reducing the rate
      of complications, including foot and ankle amputations or limb loss. Attempting
      reconstruction at Eichenholtz stages I and II carries the risk of infection and
      loss of fixation. It is advisable to limit surgical reconstruction to Eichenholtz
      stage III in the absence of any evidence of infection or vascular insufficiency.
      Achilles lengthening or gastrocnemius-soleus release is an essential initial step
      in surgery. Addressing the medial foot column first is a key to a successful
      reconstruction.

PMID- 27865315
TI  - Surgical Treatment Options for the Diabetic Charcot Hindfoot and Ankle Deformity.
AB  - Charcot neuroarthropathy is associated with progressive, noninfectious,
      osteolysis-induced bone and joint destruction. When the ankle and/or hindfoot is
      affected by the destruction process, management is further complicated with
      collapse and destruction of the talar body, which increases instability around
      the ankle. In this patient population, arthrodesis is the most commonly used
      surgical procedure. Internal fixation, external fixation, or a combination of
      both can be used for the treatment. Decision making between them should be
      individualized according to the patient characteristics.

PMID- 27865316
TI  - Soft Tissue Reconstruction Pyramid for the Diabetic Charcot Foot.
AB  - Foot and ankle ulcerations in patients with diabetic Charcot neuroarthropathy
      (DCN) occur frequently and can be challenging to address surgically when
      conservative care fails. Patients with acute or chronic diabetic foot ulcers
      (DFU) are at continued risk for development of osteomyelitis, septic arthritis,
      gas gangrene, and potential lower extremity amputation. Concurrent vasculopathy
      and peripheral neuropathy as well as uncontrolled medical comorbidities
      complicate the treatment approach. In addition, pathomechanical forces left
      untreated may contribute to DFU recurrence in this patient population. This
      article outlines in detail the stepwise approach and options available for
      durable soft tissue coverage in the DCN patient.

PMID- 27865317
TI  - Revisional Surgery of the Diabetic Charcot Foot and Ankle.
AB  - Charcot neuroarthropathy (CN) is a difficult problem for the foot and ankle
      surgeon. If surgery is required, little is known or available regarding the best
      methods and timing. When the initial attempt of reconstruction fails, revision of
      CN is even more demanding. One must take in to account all aspects, including
      nutrition, vascular status, infection control, short- and long-term blood glucose
      management, as well as other factors requiring laboratory monitoring and consult
      services. Once optimized, the biomechanics of the deformity can be addressed and
      decisions can be made on fixation devices.

PMID- 27865318
TI  - Medical Imaging in Differentiating the Diabetic Charcot Foot from Osteomyelitis.
AB  - Diabetic Charcot neuroarthropathy (DCN) poses a great challenge to diagnose in
      the early stages and when plain radiographs do not depict any initial signs of
      osseous fragmentation or dislocation in a setting of a high clinical index of
      suspicion. Medical imaging, including magnetic resonance imaging, computed
      tomography, and advanced bone scintigraphy, has its own unique clinical
      indications when treating the DCN with or without concomitant osteomyelitis. This
      article reviews different clinical case scenarios for choosing the most accurate
      medical imaging in differentiating DCN from osteomyelitis.

PMID- 27865319
TI  - Circular External Fixation as a Primary or Adjunctive Therapy for the Podoplastic
      Approach of the Diabetic Charcot Foot.
AB  - Numerous techniques have been described for surgical management of the diabetic
      Charcot foot. External fixation has become a main surgical tool for the
      reconstructive foot and ankle surgeon when dealing with the ulcerated diabetic
      Charcot foot. In the presence of an open wound and/or osteomyelitis, staged
      reconstruction with circular external fixation becomes ideal for salvage of the
      diabetic lower extremity. Also, circular external fixation can provide
      simultaneous compression and stabilization, correct the underlying osseous or
      soft tissue deformities, and surgically offload the diabetic Charcot foot. This
      article describes a variety of circular external fixation applications for the
      diabetic Charcot foot.

PMID- 27865320
TI  - The Diabetic Charcot Foot and Ankle: A Multidisciplinary Team Approach.

PMID- 27865321
TI  - Chest Tubes: Generalities.
AB  - Insertion, management, and withdrawal of chest tubes is part of the routine
      activity of thoracic surgeons. The selection of the chest tube and the strategy
      for each of these steps is usually built on knowledge, practice, experience, and
      judgment. The indication to insert a chest tube into the pleural cavity is the
      presence of air or fluid within it. Various types and sizes of chest tubes are
      now commercially available.

PMID- 27865322
TI  - Thoracic Trauma: Which Chest Tube When and Where?
AB  - Clinical suspicion of hemo/pneumothorax: when in doubt, drain the chest. Stable
      chest trauma with hemo/pneumothorax: drain and wait. Unstable patient with
      dislocated trachea must be approached with drain in hand and scalpel ready.
      Massive hemo/pneumothorax may be controlled by drainage alone. The surgeon should
      not hesitate to open the chest if too much blood drains over a short period. The
      chest drainage procedure does not end with the last stitch; the second half of
      the match is still ahead. The drained patient is in need of physiotherapy and
      proper pain relief with an extended pleural space: control the suction system.

PMID- 27865323
TI  - Chest Tube Management after Surgery for Pneumothorax.
AB  - There is scant evidence on the management of chest tubes after surgery for
      pneumothorax. Most of the current knowledge is extrapolated from studies
      performed on subjects with lung cancer. This article reviews the existing
      literature with particular focus on the effect of suction and no suction on the
      duration of air leak after lung resection and surgery for pneumothorax. Moreover,
      the role of regulated suction, which seems to provide some benefit in reducing
      pneumothorax recurrence after bullectomy and pleurodesis, is discussed. Finally,
      a personal view on the management of chest tubes after surgery for pneumothorax
      is provided.

PMID- 27865324
TI  - Modern Techniques to Insert Chest Drains.
AB  - Both physicians and surgeons insert chest drains by various techniques-including
      Seldinger and "wide-bore" methods. The indications include hemothorax,
      pneumothorax, pleural effusion, and postoperative care in thoracic surgery. Given
      their invasive nature, there is significant potential for complications; however,
      this can be minimized by following a meticulous technique, which is herein
      described for both Seldinger and "wide-bore" drain insertion.

PMID- 27865325
TI  - Suction or Nonsuction: How to Manage a Chest Tube After Pulmonary Resection.
AB  - Despite several randomized trials and meta-analyses, the dilemma as to whether to
      apply suction after subtotal pulmonary resection has not been solved. The
      combination of a poorly understood pathophysiology of the air leak phenomenon and
      the inadequate quality of the published randomized trials is actually preventing
      thoracic surgeons from abandoning an empirical management of chest drains. Even
      digital systems do not seem to have made the difference so far. Based on the
      evidence of the literature, the authors propose a new air leak predictor score
      (ALPS) as a contributing step toward appropriateness in using intraoperative
      sealants, opting for an external suction and managing and chest tubes.

PMID- 27865326
TI  - When to Remove a Chest Tube.
AB  - Despite the increasing knowledge about the pleural physiology after lung
      resection, most practices around chest tube removal are dictated by personal
      preferences and experience. This article discusses recently published data on the
      topic and suggests opportunities for further investigation and future
      improvements.

PMID- 27865327
TI  - Indwelling Pleural Catheters: A Clinical Option in Trapped Lung.
AB  - Malignant pleural effusion (MPE) symptoms have a real impact on quality of life.
      Surgical approach through video-assisted thoracic surgery provides a first step
      in palliation. In patients unfit for general anesthesia, awake pleuroscopy
      represents an alternative. Sclerosing agents can be administered at the bedside
      through a chest tube. Ideal treatment of MPE should include adequate long-term
      symptom relief, minimize hospitalization, and reduce adverse effects. Indwelling
      pleural catheter (IPC) allows outpatient management of MPE through periodic
      ambulatory fluid drainage. IPC offers advantages over pleurodesis in patients
      with poor functional status who cannot tolerate pleurodesis or in patients with
      trapped lungs.

PMID- 27865329
TI  - Management of Chest Drains After Thoracic Resections.
AB  - Immediately after lung resection, air tends to collect in the retrosternal part
      of the chest wall (in supine position), and fluids in its lower part
      (costodiaphragmatic sinus). Several general thoracic surgery textbooks currently
      recommend the placement of 2 chest tubes after major pulmonary resections, one
      anteriorly, to remove air, and another into the posterior and basilar region, to
      drain fluids. Recently, several authors advocated the placement of a single chest
      tube. In terms of air and fluid drainage, this technique demonstrated to be as
      effective as the conventional one after wedge resection or uncomplicated
      lobectomy.

PMID- 27865328
TI  - Errors and Complications in Chest Tube Placement.
AB  - Chest drain placement is one of the most common surgical procedures performed in
      routine clinical practice. Despite the many benefits, chest tube insertion is not
      always a harmless procedure, and potential significant morbidity and mortality
      may exist. The aim of this article was to highlight the correct chest tube
      placement procedure and to focus on errors and clinical complications following
      its incorrect insertion into the chest.

PMID- 27865330
TI  - Chest Drainage Management: Where Are We Now?

PMID- 27865331
TI  - Lesbian, Gay, Bisexual, and Transgender Youth and Family Acceptance.
AB  - In this article, we address theories of attachment and parental acceptance and
      rejection, and their implications for lesbian, gay, bisexual, and transgender
      (LGBT) youths' identity and health. We also provide 2 clinical cases to
      illustrate the process of family acceptance of a transgender youth and a gender
      nonconforming youth who was neither a sexual minority nor transgender. Clinical
      implications of family acceptance and rejection of LGBT youth are discussed.

PMID- 27865333
TI  - Substance Abuse Prevention, Assessment, and Treatment for Lesbian, Gay, Bisexual,
      and Transgender Youth.
AB  - Knowing how to manage substance abuse in all youth is an important aspect of
      pediatric care, including providing clinically appropriate anticipatory guidance,
      monitoring, assessment, and treatment. Although most lesbian, gay, bisexual, and
      transgender (LGBT) youth do not abuse substances, as a group they experience
      unique challenges in self-identity development that put them at an increased risk
      for substance abuse. This article addresses prevention and management of
      substance use in LGBT youth relevant to pediatrics and allied professions as an
      aspect of their overall health care. It reviews basic information about substance
      abuse in youth and special considerations for LGBT youth.

PMID- 27865332
TI  - Human Immunodeficiency Virus, Other Sexually Transmitted Infections, and Sexual
      and Reproductive Health in Lesbian, Gay, Bisexual, Transgender Youth.
AB  - Lesbian, gay, bisexual, transgender (LGBT), and questioning youth represent a
      diverse population who are affected by many sexual health inequities, including
      increased risk for human immunodeficiency virus (HIV) and sexually transmitted
      infections (STIs). To provide comprehensive sexual health care for LGBT youth,
      providers should set the stage with a nonjudgmental, respectful tone. Providers
      should be competent in recognizing symptoms of STIs and HIV and aware of the most
      up-to-date screening guidelines for LGBT youth. Sexual health visits should also
      focus on prevention, including safer sex practices, HIV pre-exposure and post
      exposure prophylaxis, family planning, and immunization for hepatitis and human
      papillomavirus.

PMID- 27865334
TI  - Body Image and Eating Disorders Among Lesbian, Gay, Bisexual, and Transgender
      Youth.
AB  - Adolescence is a crucial period for emerging sexual orientation and gender
      identity and also body image disturbance and disordered eating. Body image
      distortion and disordered eating are important pediatric problems affecting
      individuals along the sexual orientation and gender identity spectrum. Lesbian,
      gay, bisexual, transgender (LGBT) youth are at risk for eating disorders and body
      dissatisfaction. Disordered eating in LGBT and gender variant youth may be
      associated with poorer quality of life and mental health outcomes. Pediatricians
      should know that these problems occur more frequently in LGBT youth. There is
      evidence that newer treatment paradigms involving family support are more
      effective than individual models of care.

PMID- 27865336
TI  - Lesbian, Gay, Bisexual, and Transgender Families.
AB  - Families headed by sexual minorities encounter unique barriers to care and health
      equity despite greater cultural acceptance and visibility. Empirical research
      suggests that children in lesbian, gay, bisexual, and transgender (LGBT) families
      develop and function comparably to those from traditional families. In helping
      families, awareness of family structure is important. The health care provider
      should be familiar with family composition, and their community, social supports,
      race/ethnic concerns, financial issues, and other vulnerabilities. Cultivating an
      office culture and practice that supports all patients to comfortably discuss
      their family history, interpersonal experiences, needs, and vulnerabilities is
      essential for excellence in clinical care.

PMID- 27865335
TI  - The Intersection of Sociocultural Factors and Health-Related Behavior in Lesbian,
      Gay, Bisexual, and Transgender Youth: Experiences Among Young Black Gay Males as
      an Example.
AB  - Intersectionality suggests that multiple social identities intersect at the
      individual or micro level of experience and reflects larger social structural
      inequities experienced on the macro level. This article uses intersectionality to
      describe how multiple stigmatized social identities can create unique challenges
      for young black gay and bisexual men (YBGBM). YBGBM exist at the intersection of
      multiple stigmatized identities compared with their majority peers. This article
      examines key intersecting identities and cultural expectations that exist in
      YBGBM and how those factors may predispose young men to adverse health outcomes
      and health inequality.

PMID- 27865337
TI  - What the Primary Care Pediatrician Needs to Know About Gender Incongruence and
      Gender Dysphoria in Children and Adolescents.
AB  - The recognition and acknowledgment that gender identity and birth-assigned sex
      may be incongruent in children and adolescents have evolved in recent decades.
      Transgender care for children and adolescents has developed and is now more
      widely available. Controversies exist, however, around clinical management of
      gender dysphoria and gender incongruence in children and adolescents. Clinical
      guidelines are consensus based and research evidence is limited. Puberty
      suppression as part of clinical management has become a valuable element of
      adolescent transgender care, but long-term evidence of success is limited. These
      uncertainties should be weighed against the risk of harming a transgender
      adolescent when medical intervention is denied.

PMID- 27865339
TI  - Development and Mental Health of Lesbian, Gay, Bisexual, or Transgender Youth in
      Pediatric Practice.
AB  - Assessing, monitoring, and supporting children and adolescents' mental health are
      integral parts of comprehensive pediatric primary care. These are especially
      relevant for LGBT youth, who frequently experience unique stressors, often
      including having an identity different from family and peer expectations, whether
      to reveal it, and stigma like peer bullying, family rejection, social
      intolerance, and self nonacceptance. Pediatricians should know key mental health
      practice principles for LGBT youth, how to adapt these to various pediatric
      settings, the continuum of mental health interventions, and their local
      resources. Practice principles in pediatric care for LGBT youth and examples of
      their implementation are discussed.

PMID- 27865340
TI  - Stigma and Minority Stress as Social Determinants of Health Among Lesbian, Gay,
      Bisexual, and Transgender Youth: Research Evidence and Clinical Implications.
AB  - In this article, we review theory and evidence on stigma and minority stress as
      social/structural determinants of health among lesbian, gay, bisexual, and
      transgender (LGBT) youth. We discuss different forms of stigma at individual (eg,
      identity concealment), interpersonal (eg, victimization), and structural (eg,
      laws and social norms) levels, as well as the mechanisms linking stigma to
      adverse health outcomes among LGBT youth. Finally, we discuss clinical (eg,
      cognitive behavioral therapy) and public health (eg, antibullying policies)
      interventions that effectively target stigma-inducing mechanisms to improve the
      health of LGBT youth.

PMID- 27865338
TI  - Caring for Lesbian, Gay, Bisexual, Transgender, and Questioning Youth in
      Inclusive and Affirmative Environments.
AB  - Lesbian, gay, bisexual, transgender, queer and questioning (LGBTQ) youth may
      experience interpersonal and structural stigma within the health care
      environment. This article begins by reviewing special considerations for the care
      of LGBTQ youth, then turns to systems-level principles underlying inclusive and
      affirming care. It then examines specific strategies that individual providers
      can use to provide more patient-centered care, and concludes with a discussion of
      how clinics and health systems can tailor clinical services to the needs of LGBTQ
      youth.

PMID- 27865341
TI  - Bullying Among Lesbian, Gay, Bisexual, and Transgender Youth.
AB  - Bullying of lesbian, gay, bisexual, and transgender (LGBT) youth is prevalent in
      the United States, and represents LGBT stigma when tied to sexual orientation
      and/or gender identity or expression. LGBT youth commonly report verbal,
      relational, and physical bullying, and damage to property. Bullying undermines
      the well-being of LGBT youth, with implications for risky health behaviors, poor
      mental health, and poor physical health that may last into adulthood.
      Pediatricians can play a vital role in preventing and identifying bullying,
      providing counseling to youth and their parents, and advocating for programs and
      policies to address LGBT bullying.

PMID- 27865342
TI  - Lesbian, Gay, Bisexual, and Transgender Youth.

PMID- 27865344
TI  - Erratum.

PMID- 27865345
TI  - Oral delivery of peptides: opportunities and issues for translation.

PMID- 27865343
TI  - Introduction to Lesbian, Gay, Bisexual, and Transgender Youth Health.

PMID- 27865346
TI  - Maternal fat-soluble vitamins, brain development, and regulation of feeding
      behavior: an overview of research.
AB  - Recent research shows a link between vitamin intake during pregnancy and
      offspring health. Inadequate intakes of water-soluble vitamins during pregnancy
      lead to obesity and characteristics of the metabolic syndrome, concurrent with
      altered developments in food intake regulatory pathways. Few studies, however,
      have reported on the effects of fat-soluble vitamins (A, D, E, and K) on the
      development of food intake regulatory pathways. The majority of studies to date
      have focused on associations between inadequate and high intakes of folic acid
      and vitamin D and neurocognitive development of the offspring. Hence, the
      objective of this review is to present an evaluation of the role of maternal
      vitamins A, D, E, and K in brain development and function of neural pathways that
      regulate feeding behaviors. PubMed and Google Scholar were searched from 1975
      through September, 2016. Most studies supporting a role for fat-soluble vitamins
      in regulating brain development and associated behaviors have been conducted in
      animal and cell models, leaving uncertain their relevance to neurocognitive
      development and function in humans. Nevertheless, although current research on
      defining the role of maternal fat-soluble vitamins in offspring's brain
      development is limited, it is sufficient to warrant further investigations on
      their impact when intake amounts during pregnancy are not only inadequate but
      also exceed requirements.

PMID- 27865347
TI  - Gestational food restriction decreases placental interleukin-10 expression and
      markers of autophagy and endoplasmic reticulum stress in murine intrauterine
      growth restriction.
AB  - Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often
      results in short- and long-term sequelae for offspring. The mechanisms underlying
      IUGR are poorly understood, but it is known that healthy placentation is
      essential for nutrient provision to fuel fetal growth, and is regulated by
      immunologic inputs. We hypothesized that in pregnancy, maternal food restriction
      (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the
      placenta, leading to increased cellular stress and death. Our specific objectives
      were to evaluate (1) key cytokines (eg, IL-10) that regulate maternal-fetal
      tolerance, (2) cellular processes (autophagy and endoplasmic reticulum [ER]
      stress) that are immunologically mediated and important for cellular survival and
      functioning, and (3) the resulting IUGR phenotype and placental histopathology in
      this animal model. After subjecting pregnant mice to mild and moderate FR from
      gestational day 10 to 19, we collected placentas and embryos at gestational day
      19. We examined RNA sequencing data to identify immunologic pathways affected in
      IUGR-associated placentas and validated messenger RNA expression changes of genes
      important in cellular integrity. We also evaluated histopathologic changes in
      vascular and trophoblastic structures as well as protein expression changes in
      autophagy, ER stress, and apoptosis in the mouse placentas. Several
      differentially expressed genes were identified in FR compared with control mice,
      including a considerable subset that regulates immune tolerance, inflammation,
      and cellular integrity. In summary, maternal FR decreases the anti-inflammatory
      effect of IL-10 and suppresses placental autophagic and ER stress responses,
      despite evidence of dysregulated vascular and trophoblast structures leading to
      IUGR.

PMID- 27865348
TI  - Nutrient restriction of glucose or serum results in similar proteomic expression
      changes in 3D colon cancer cell cultures.
AB  - Nutrient restriction, also known as caloric restriction, has been extensively
      examined for its positive impact on lifespan, immune system boost, and aging. In
      addition, nutrient restriction is implicated in decreasing cancer initiation and
      progression. Given the phenotypic changes associated with nutrient restriction,
      we hypothesized significant protein expression alterations must be associated
      with caloric restriction. To compare the molecular and phenotypic changes caused
      by glucose restriction and fetal bovine serum restriction there is need for an
      efficient model system. We establish 3-dimensional cell culture models, known as
      spheroids, in the HCT 116 colorectal cancer cell line as a high throughput model
      for studying the proteomic changes associated with nutrient restriction. Flow
      cytometry was used to assess apoptosis and autophagy levels in the spheroids
      under nutrient restriction. Isobaric tags for relative and absolute
      quantification and liquid chromatography tandem mass spectrometry were used to
      determine differential protein abundances between the nutrient restriction
      conditions. We identified specific proteins that have implications in cancer
      progression and metastasis that are differentially regulated by restriction of
      either glucose or serum. These proteins include the up-regulation of sirtuin 1
      and protein inhibitor of activated STAT 1 and down-regulation of multi-drug
      resistance protein and Zinc finger and BTB domain-containing protein 7A. The
      results indicate nutrient restriction causes lower apoptotic and higher autophagy
      rates in HCT 116 spheroids. In addition, proteins shown to be differentially
      regulated by both glucose and serum restriction were similarly regulated.

PMID- 27865349
TI  - Whey protein increases muscle weight gain through inhibition of oxidative effects
      induced by resistance exercise in rats.
AB  - Whey protein (WP) is known for its nutritional value and antioxidant properties.
      The aim of this study was to evaluate whether the antioxidant properties of WP
      could contribute to muscle weight gain in response to resistance exercise (RE).
      We hypothesized that WP ingestion could increase muscle weight gain in rats
      subjected to an RE program, through inhibition of oxidative effects induced by
      high-intensity RE. Thirty-two male Fischer rats were randomly assigned to control
      sedentary, control exercised, WP sedentary, and WP exercised groups (n=8/group).
      The RE consisted of inducing the rats to perform sets of jumps for 8 weeks. Body
      and muscle weight gains, muscle glutathione content, histopathology, muscle
      antioxidant enzyme activities, and gene expression were evaluated. Body and
      muscle weight gains of exercised rats fed WP were higher than those of control
      exercised rats. Concomitantly, RE induced an increase in phagocyte infiltration,
      protein oxidation, and down-regulation of glutathione peroxidase and gamma
      glutamylcysteine synthetase messenger RNA expression in gastrocnemius muscle
      (P<.05), effects that were inhibited by WP ingestion. Cytosolic superoxide
      dismutase and catalase messenger RNA expression were reduced only by RE (P<.05),
      and muscle glutathione content was increased only by WP (P<.05) with no
      significant interaction observed (P>.05). These findings suggest that differences
      in body and muscle weight gain in exercised rats fed control or WP diets were
      mediated, in part, by the antioxidant properties of WP, and indicate that when
      associated with RE, WP represents a nutritional aid to support muscle growth.

PMID- 27865350
TI  - The fruit of Acanthopanax senticosus (Rupr. et Maxim.) Harms improves insulin
      resistance and hepatic lipid accumulation by modulation of liver adenosine
      monophosphate-activated protein kinase activity and lipogenic gene expression in
      high-fat diet-fed obese mice.
AB  - Obesity-associated insulin resistance is a major risk factor for most metabolic
      diseases, including dyslipidemia and type 2 diabetes. Acanthopanax senticosus
      (Rupr. et Maxim.) Harms (Goka) root has been used in traditional Chinese medicine
      for treatment of diabetes and other conditions; however, little is known about
      the effects of Goka fruit (GF). Goka fruit is rich in anthocyanin, which has
      beneficial effects on obesity and insulin resistance via activation of adenosine
      monophosphate-activated protein kinase (AMPK). We hypothesized that GF can
      improve obesity-associated insulin resistance. The aim of the present study was
      to investigate whether GF improves insulin resistance in high-fat diet (HFD)
      induced obese mice. High-fat diet mice treated with GF (500 and 1000 mg/kg) for
      12 weeks showed an improved glucose tolerance and insulin sensitivity, as well as
      reduced plasma insulin and liver lipid accumulation. Moreover, GF administration
      to HFD mice resulted in down-regulation of fatty acid synthase expression and up
      regulation of cholesterol 7-alpha-hydroxylase expression in the liver. Notably,
      AMPK phosphorylation in the liver increased after GF administration. In summary,
      GF supplementation improved obesity-associated insulin resistance and hepatic
      lipid accumulation through modulation of AMPK activity and lipid metabolism
      associated gene expression.

PMID- 27865351
TI  - Quercetin relaxes guinea pig gallbladder strips.
AB  - Quercetin, a phytoestrogen and flavonoid, relaxes intestinal and vascular smooth
      muscle. The purpose of this study was to determine if quercetin had an effect on
      gallbladder smooth muscle. An in vitro technique was used to determine the
      effects of quercetin on gallbladder strips and which system(s) mediated the
      relaxation. Paired t tests were used; differences between means of P < .05 were
      considered significant. Adding quercetin before cholecystokinin or KCl produced a
      significant (P < .001) decrease in the amount of tension (0.80 +/- 0.04 vs 0.48
      +/- 0.04 g cholecystokinin octapeptide and 0.8 +/- 0.06 vs 0.54 +/- 0.05 g KCl,
      respectively). When the protein kinase C (PKC) inhibitors bisindolymaleimide IV
      and chelerythrine Cl- were simultaneously, a significant (P < .001) reduction in
      the quercetin-induced relaxation (45.7% +/- 4.3% vs 27.6% +/- 3.4%) was observed.
      To determine if protein kinase A (PKA) mediated the quercetin-induced relaxation,
      PKA inhibitor 14-22 amide myristolated was used. It significantly (P < .05)
      decreased the amount (40.4% +/- 3.7% vs 34.5% +/- 3.3%) of quercetin-induced
      relaxation. The use of 2-APB also significantly (P < .001) reduced the amount of
      quercetin-induced relaxation (51.2% +/- 3.5% vs 14.8% +/- 3.6%). l-NG-methyl-l
      arginine acetate salt, a nitric oxide synthase inhibitor, significantly (P < 001)
      decreased the quercetin-induced relaxation (45.7% +/- 4.2% vs 35.2% +/- 3.6%).
      KT5823, a PKC inhibitor, had no effect on the quercetin-induced relaxation.
      Quercetin blocked extracellular Ca2+ entry which affected downstream events such
      as activation of PKC, PKA, intracellular Ca2+ release, and activation of nitric
      oxide synthase. Quercetin relaxed cholecystokinin octapeptide and KCl-induced
      tension in a concentration dependent manner. Thus quercetin-induced relaxation
      was mediated by multiple signaling pathways.

PMID- 27865352
TI  - Plum polyphenols inhibit colorectal aberrant crypt foci formation in rats:
      potential role of the miR-143/protein kinase B/mammalian target of rapamycin
      axis.
AB  - The nutritional prevention of aberrant crypt foci by polyphenols may be a crucial
      step to dietary cancer prevention. The objective of this study was to determine
      the underlying mechanisms that contribute to the anti-inflammatory and
      antitumorigenic properties of plum (Prunus salicina L.) polyphenols, including
      chlorogenic acid and neochlorogenic acid, in azoxymethane (AOM)-treated rats. The
      hypothesis was that plum polyphenolics suppress AOM-induced aberrant crypt foci
      formation through alterations in the protein kinase B (AKT)/mammalian target of
      rapamycin (mTOR) pathway and relative micro-RNA expressions. Sprague-Dawley rats
      (n=10/group) received plum beverage (1346mg gallic acid equivalents/L) or a
      control beverage ad libitum for 10 weeks with subcutaneous injections of AOM
      (15mg/kg) at weeks 2 and 3. Results show that the consumption of the plum
      beverage decreased the number of dysplastic aberrant crypt foci by 48% (P<.05)
      and lowered proliferation of mucosal cells by 24% (P<.05). The plum beverage
      decreased the activity of glutathione peroxidase, superoxide dismutase, and
      catalase in mucosal scrapings, as well as the superoxide dismutase activity in
      serum. The results were accompanied by a down-regulation of proinflammatory
      enzymes nuclear factor kappaB, nitric oxide synthase, cyclooxygenase-2, and
      vascular cell adhesion molecule 1 messenger RNA. Plum inhibited the expression of
      AKT and mTOR messenger RNA, phosphorylated AKT, mTOR, and hypoxia-inducible
      factor-1alpha protein levels, and the ratio of the phosphorylated/total protein
      expression of mTOR. Also, the plum beverage increased the expression of miR-143,
      which is involved in the regulation of AKT. These results suggest that plum
      polyphenols may exhibit a chemopreventive potential against colon carcinogenesis
      by impacting the AKT/mTOR pathway and miR-143.

PMID- 27865353
TI  - Maintenance of cytosolic calcium is crucial to extend l-arginine therapeutic
      benefits during continuous dosing.
AB  - The therapeutic benefits associated with short-term l-arginine supplementation
      are lost during continuous dosing. AMP-activated protein kinase (AMPK) functional
      modulation has been correlated with l-arginine therapeutic effectiveness, and
      with tolerance development during continuous supplementation. However, the
      metabolic link that is responsible for AMPK functional modulation during
      continuous l-arginine exposure is currently not known. To explore this, we
      incubated HUVECs for 7 days with 100 MUmol/L l-arginine, in the presence or
      absence of other agents; and monitored their effects for eNOS function, and on
      tolerance sparing effects (viz, cellular glucose accumulation, and oxidative
      stress). HUVEC co-incubation with 100 MUmol/L l-arginine and <=1200 mg/mL calcium
      (Ca2+) for 7 days avoided tolerance development, with an at least 1-fold increase
      in the eNOS and AMPK functional activity; and an 1-fold increase in overall
      cellular glucose uptake. The overall cellular cytosolic Ca2+was below 200 nmol/L,
      with no change in cellular glucose and superoxide/peroxynitrite (O2*-/ONOO-)
      level from control. However, tolerance sparing effects of at least 70% decrease
      in eNOS and AMPK functional response, with an 1-fold reduction in glucose uptake,
      and at least 2-fold increase in O2*-/ONOO- were observed in cells exposed for 7
      days to 100 MUmol/L l-arginine at Ca2+co-incubation concentration of >1200 mg/mL.
      The >1200 mg/mL Ca2+ co-incubation condition, also improved the overall cellular
      Ca2+to >200 nmol/L. Similar tolerance response was observed in cells co-treated
      with 100 MUmol/L l-arginine and <=1200 mg/mL Ca2+ in the presence of Ca2+ influx
      inhibitor (20 MUmol/L 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid),
      or eNOS activity inhibitor (30 MUmol/L l-NG-nitroarginine methyl ester). No
      tolerance response was seen in cells incubated for 7 days with 100 MUmol/L l
      arginine and <=1200 mg/mL Ca2+; even in the presence of the inhibitor for
      cellular glucose induction (30 MUmol/L 5-chloro-2-(n-(2,5
      dichlorobenzenesulfonamide))-benzoxazole). The present study thus provides the
      first definitive evidence that shows the need to maintain cytosolic Ca2+ within a
      threshold limit of less than 200 nmol/L to extend l-arginine therapeutic efficacy
      during continuous dosing, without any potential tolerance development.

PMID- 27865354
TI  - Vitamin D supplementation reduces insulin resistance in Japanese adults: a
      secondary analysis of a double-blind, randomized, placebo-controlled trial.
AB  - Higher circulating 25-hydroxyvitamin D (25[OH]D) concentration has been linked to
      a lower prevalence of insulin resistance and type 2 diabetes mellitus. However,
      randomized controlled trials have not clarified the effect of vitamin D
      supplementation on insulin resistance in healthy adults. The objective of this
      study was to assess the effect of vitamin D supplementation for 1 year on insulin
      resistance; the study was a secondary analysis of a clinical trial. We
      hypothesized that increased 25(OH)D concentration after vitamin D supplementation
      for 1 year would significantly improve insulin resistance. Ninety-six healthy
      adults participated in this study, of whom 81 completed the study. The
      participants randomly received daily either 420 IU vitamin D3 or placebo in a
      double-blind manner for 1 year. The levels of fasting insulin, glucose, and other
      parameters were assessed at baseline and after 1 year of intervention.
      Homeostasis model assessment of insulin resistance index was calculated from
      insulin and glucose levels. Visceral fat area and physical activity were also
      investigated. Serum 25(OH)D and 1,25-dihydroxyvitamin D concentrations were
      significantly increased by approximately 29.5 nmol/L and 7.0 pg/mL, respectively,
      after 1-year vitamin D supplementation. After vitamin D supplementation, fasting
      glucose levels and values of homeostasis model assessment of insulin resistance
      index significantly decreased from 88.3 to 85.3 mg/dL (P < .01) and 1.17 to 0.84
      (P < .01), respectively, and the results were independent of physical activity
      and visceral fat accumulation. In conclusion, the present study showed that
      vitamin D supplementation for 1 year effectively improves fasting glucose level
      and insulin resistance in healthy Japanese adults.

PMID- 27865355
TI  - White sesame seed water-soluble fraction enhances human neuroblast cell viability
      via an anti-apoptotic mechanism.
AB  - Defatted sesame seed flour is recovered as a byproduct after oil extraction and
      is usually considered a waste product. Previously, we showed that water-soluble
      fractions purified from defatted white and gold sesame seed flour exhibited good
      antioxidant activity in vitro. We also identified ferulic acid and vanillic acid
      as the bioactive antioxidants in both white and gold sesame seed water-soluble
      fractions (WS-wsf and GS-wsf, respectively). In this study, we hypothesized that
      WS-wsf and GS-wsf may have neuroprotective effects due to their antioxidant
      potential. Treatment with WS-wsf for 24 hours enhanced human neuroblastoma SH
      SY5Y cell viability and proliferation, while GS-wsf, ferulic acid, and vanillic
      acid did not show similar effects. In addition, WS-wsf (1-3 mg/mL) significantly
      and dose-dependently protected SH-SY5Y cells against camptothecin-induced
      apoptosis, suggesting the involvement of an anti-apoptosis mechanism in the
      neuroprotective effects of WS-wsf. In fact, treatment with WS-wsf significantly
      decreased the mRNA expression levels of pro-apoptotic Bax and p53 genes. WS-wsf
      also enhanced Bcl-2 protein level and Akt phosphorylation. Taken together, this
      study showed that WS-wsf has interesting neuroprotective potential via an anti
      apoptotic mechanism, which is independent from its antioxidant capacity.

PMID- 27865356
TI  - Temporal trends in dietary supplement prescriptions of United States military
      service members suggest a decrease in pyridoxine and increase in vitamin D
      supplements from 2005 to 2013.
AB  - Dietary supplements (DSs) can be obtained over-the-counter but can also be
      prescribed by health-care providers for therapeutic reasons. Few studies have
      documented this later source despite the fact that 79% of physicians and 82% of
      nurses have recommended DSs to patients. This investigation assessed prevalence
      and temporal trends in oral DS prescriptions filled by all United States service
      members (SMs) from 2005 to 2013 (n = 1 427 080 +/- 22 139, mean +/- standard
      deviation (SD)/y). We hypothesize that there would be temporal variations in
      specific types of DSs. Data obtained from Department of Defense Pharmacy Data
      Transaction System were grouped by American Hospital Formulary System
      pharmacologic-therapeutic classifications and prevalence examined over time.
      About 11% of SMs filled one or more DS prescriptions of 235 180 +/- 4926 (mean +/
      SD) prescriptions/y over the 9-year period. Curve-fitting techniques indicated
      significant linear declines over time for multivitamins (P = .004), iron
      preparations (P < .001), antacids (P < .001), and vitamin B and B complex
      vitamins (P < .001). There were significant quadratic trends indicating a rise in
      early years followed by a leveling off in later years for replacement
      preparations (P < .001) and vitamin C (P < .001). There were significant
      quadratic trends (P < .001) for vitamin E indicating a decline in early years and
      leveling off in later years, and vitamin D indicating little change in early
      years followed by a large rise subsequently (P < .001). This study identified
      temporal trends in specific DS categories that may be associated with changing
      perceptions of prescribers and/or patients of the appropriate roles of DSs in
      medicine and public health.

PMID- 27865359
TI  - Getting the Most from Your Cytology Samples.

PMID- 27865358
TI  - Low daily dose of 3 mg monacolin K from RYR reduces the concentration of LDL-C in
      a randomized, placebo-controlled intervention.
AB  - Hypercholesterolemia and elevated homocysteine concentrations are associated with
      cardiovascular risk. Previous studies have demonstrated a cholesterol-lowering
      effect of red yeast rice (RYR) supplements which contained 5 to 10 mg of
      monacolin K. We hypothesized that the intake of a low monacolin K dose may
      likewise reduce low-density lipoprotein-cholesterol (LDL-C) and other plasma
      lipids. In secondary analyses, we tested the homocysteine lowering effect of
      folic acid, which was also included in the study preparation. Therefore, we
      conducted a randomized, double-blind, and placebo-controlled intervention study.
      One hundred forty-two nonstatin-treated participants with hypercholesterolemia
      (LDL-C >= 4.14 <= 5.69 mmol/L) were randomized to the supplement group with RYR
      or the placebo group. Participants of the supplement group consumed 3 mg
      monacolin K and 200 MUg folic acid per day. A significant (P < .001) reduction of
      LDL-C (-14.8%), total cholesterol (-11.2%), and homocysteine (-12.5%) was
      determined in the supplement group after 12 weeks. A total of 51% of the
      participants treated with RYR achieved the limit of LDL-C <4.14 mmol/L advised
      and 26% reached the threshold level of homocysteine <10 MUmol/L. No significant
      changes were exhibited within the placebo group. Other parameters remained
      unchanged and no intolerances or serious adverse events were observed. In
      conclusion, we demonstrated that a low dose of daily 3 mg monacolin K from RYR
      reduces the concentration of LDL-C; a risk factor for cardiovascular diseases.

PMID- 27865357
TI  - Younger and older ages and obesity are associated with energy intake
      underreporting but not overreporting in Japanese boys and girls aged 1-19 years:
      the National Health and Nutrition Survey.
AB  - Evidence on the magnitude and nature of misreporting of food intake in non
      Western children and adolescents is sparse. We investigated the hypothesis that
      under- and overreporting of energy intake (EI) is prevalent and associated with
      some characteristics in 3866 Japanese boys and girls aged 1-19 years using data
      from the 2012 National Health and Nutrition Survey, Japan. Each individual's EI
      was calculated based on a 1-day semiweighed household dietary record, including
      information on approximate proportions by which each dish was divided among the
      family members. Under-, acceptable, and overreporters of EI were identified by 2
      methods: based on the 95% confidence limits (1) for agreement between the ratio
      of EI to basal metabolic rate (BMR) and a physical activity level for sedentary
      lifestyle (1.55) and (2) of the expected ratio of EI to estimated energy
      requirement (EER) of 1.0. BMR was calculated using Schofield's equations. EER was
      calculated using equations from the US Dietary Reference Intakes, assuming "low
      active" level of physical activity. Percentages of under-, acceptable, and
      overreporters were 2.4%, 97.0%, and 0.5%, respectively, based on EI/BMR and 3.2%,
      95.4%, and 1.4%, respectively, based on EI/EER. Underreporting was associated
      with the youngest (1-5 years) and oldest (15-19 years) age groups and with
      obesity. Overreporting was not associated with any of the variables examined. In
      conclusion, although overall mean EI obtained from the National Health and
      Nutrition Survey, Japan seemed plausible in Japanese boys and girls, younger and
      older ages and obesity were associated with EI underreporting but not
      overreporting.

PMID- 27865360
TI  - Langerhans cell number is a strong and independent prognostic factor for head and
      neck squamous cell carcinomas.
AB  - OBJECTIVES: Head and neck squamous cell carcinomas (HNSCCs) exhibit great
      biological heterogeneity and relatively poor prognosis. Tobacco and alcohol
      consumption is involved in the cause of the majority of these cancers, but over
      the last several years, Human Papilloma Virus (HPV) infection has increased
      specifically in oropharyngeal cancers and become an additional risk factor. Here,
      we evaluated the number of Langerhans cells (LCs) in HNSCC and reporting its
      prognostic power in comparison to other risk factors. MATERIALS AND METHODS: Our
      clinical series was composed of 25 tumor-free peritumoral epithelium, 64 low
      grade dysplasia, 54 high-grade dysplasia and 125 carcinoma samples. HPV was
      detected by E6/E7 qPCR and p16 immunohistochemistry. CD1a-positive LCs were
      counted in intra-tumoral and stromal compartments as well as lymph nodes. MIP
      3alpha was assessed in carcinomas using immunohistochemistry. RESULTS: Univariate
      Cox regression analyses demonstrated that high LC number is associated with
      longer recurrence-free survival in both intra-tumoral and stromal compartments
      and longer overall survival in stromal compartment. Tobacco and alcohol habits,
      but not HPV status, are also correlated with poor prognoses in terms of
      recurrence. Multivariate analyses reported stromal LC number as a strong
      prognostic factor independent of tobacco, alcohol and HPV status. Moreover, LC
      number is higher in tumors and invaded lymph nodes than dysplastic lesions but it
      decreases in HPV-positive cancer patients. Further, LC number correlates with MIP
      3alpha expression. CONCLUSION: These findings suggest that LC number is a
      significant and independent prognostic factor for HNSCC. LC infiltration is
      increased in cancer lesions but decrease with HPV infection.

PMID- 27865362
TI  - Lateral lymph node recurrence after total thyroidectomy and central neck
      dissection in patients with papillary thyroid cancer without clinical evidence of
      lateral neck metastasis.
AB  - BACKGROUND: This study analyzed the incidence, pattern, and predictive factors
      for lateral lymph node (LN) recurrence in patients with papillary thyroid cancer
      (PTC) without clinical evidence of lateral LN metastasis. METHODS: A
      retrospective analysis was performed on 246 patients with PTC who underwent total
      thyroidectomy and central neck dissection from 2004 to 2010. None of the patients
      had clinical evidence of lateral LN metastasis at the time of diagnosis.
      Predictive factors for lateral LN recurrence were evaluated using the chi-square
      test. Binary logistic regression was used for the multivariate analysis.
      Recurrence-free survival rates were estimated by the Kaplan-Meier and Cox
      regression methods. RESULTS: Of the 246 patients, 11 (4.5%) developed lateral LN
      recurrence with a median follow-up of 49months. In the multivariate analysis,
      tumor size >1cm (odds ratio [OR], 8.14; 95% confidence interval [CI], 1.01-65.68;
      p=0.049) and central LN metastasis (OR, 10.59; 95% CI, 1.32-85.17; p=0.026) were
      independent predictive factors of lateral LN recurrence. Especially, extranodal
      extension of a metastatic central LN (OR, 38.82; 95% CI, 5.71-264.10; p<0.001)
      was an independent predictor of lateral LN recurrence. CONCLUSIONS: Tumor size
      and central LN metastasis were independent predictors of lateral LN recurrence in
      patients with PTC without initial clinical lateral neck metastasis who underwent
      total thyroidectomy and central neck dissection. Close surveillance may be
      necessary for early detection of lateral LN recurrence in PTC patients with tumor
      size ?1cm, and central LN metastasis with extranodal extension.

PMID- 27865361
TI  - Diagnosis of HPV driven oropharyngeal cancers: Comparing p16 based algorithms
      with the RNAscope HPV-test.
AB  - BACKGROUND: Accurate identification of HPV-driven oropharyngeal cancer (OPC) is a
      major issue and none of the current diagnostic approaches is ideal. An in situ
      hybridization (ISH) assay that detects high-risk HPV E6/E7 mRNA, called the
      RNAscope HPV-test, has been recently developed. Studies have suggested that this
      assay may become a standard to define HPV-status. METHODS: To further assess this
      test, we compared its performance against the strategies that are used in routine
      clinical practice: p16 immunohistochemistry (IHC) as a single test and algorithms
      combining p16-IHC with HPV-DNA identification by PCR (algorithm-1) or ISH
      (algorithm-2). RESULTS: 105 OPC specimens were analyzed. The prevalence of HPV
      positive samples varied considerably: 67% for p16-IHC, 54% for algorithm-1, 61%
      for algorithm-2 and 59% for the RNAscope HPV-test. Discrepancies between the
      RNAscope HPV-test and p16-IHC, algorithm-1 and 2 were noted in respectively
      13.3%, 13.1%, and 8.6%. The 4 diagnostic strategies were able to identify 2
      groups with different prognosis according to HPV-status, as expected. However,
      the greater survival differential was observed with the RNAscope HPV-test [HR:
      0.19, 95% confidence interval (CI), 0.07-0.51, p=0.001] closely followed by
      algorithm-1 (HR: 0.23, 95% CI, 0.08-0.66, p=0.006) and algorithm-2 (HR: 0.26, 95%
      CI, 0.1-0.65, p=0.004). In contrast, a weaker association was found when p16-IHC
      was used as a single test (HR: 0.33, 95% CI, 0.13-0.81, p=0.02). CONCLUSIONS: Our
      findings suggest that the RNAscope HPV-test and p16-based algorithms perform
      better that p16 alone to identify OPC that are truly driven by HPV-infection. The
      RNAscope HPV-test has the advantage of being a single test.

PMID- 27865364
TI  - Induction chemotherapy with docetaxel, cisplatin and fluorouracil followed by
      concurrent chemoradiotherapy or chemoradiotherapy alone in locally advanced non
      endemic nasopharyngeal carcinoma.
AB  - OBJECTIVES: To evaluate the efficacy of induction chemotherapy with docetaxel,
      cisplatin and fluorouracil (TPF) followed by concurrent chemoradiotherapy
      (IC+CCRT) or CCRT alone in non-endemic locally advanced nasopharyngeal carcinoma
      (NPC) patients. MATERIALS AND METHODS: Data of 106 patients with NPC treated from
      January 1999 to June 2012 with IC+CCRT (n=58) or CCRT alone (n=48) were
      retrospectively reviewed. RESULTS: Median follow-up was 6.4years. Distribution of
      age, performance status, stage and concurrent chemotherapy regimen were
      imbalanced between the two groups. The 5-year overall survival (OS) and
      progression-free survival (PFS) were not significantly different between IC+CCRT
      and CCRT groups (OS: 78.3% vs. 82.7%, p=0.77; PFS: 72.5% vs. 68.2%, p=0.81,
      respectively). There were less total cumulative incidence of grade 3-4 late
      radiation morbidity in the IC+CCRT group (44.8% vs. 70.8%, p=0.01). Five-year OS
      for patients with post-IC complete response (CR), partial response (PR) and
      stable disease (SD) sub-groups were 100%, 79.4% and 60%, respectively.
      CONCLUSION: Compared with CCRT alone, IC (TPF regimen)+CCRT did not improve OS or
      PFS in patients with NPC, but less grade 3-4 late toxicities were observed.
      Responsiveness of IC may provide additional prognostic information.

PMID- 27865363
TI  - Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx.
AB  - OBJECTIVE: The rapid worldwide rise in incidence of human papillomavirus (HPV)
      positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies
      confirming this disease as an entity distinct from traditional OPSCC. Based on
      pathology, surgical studies have revealed prognosticators specific to HPV
      positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)
      classification do not differentiate for survival, demonstrating the need for new,
      HPV-specific OPSCC staging. The objective of this study was to define a
      pathologic staging system specific to HPV-positive OPSCC. METHODS: Data were
      assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0)
      of 704 patients from five cancer centers. Analysis was performed for (a) the
      AJCC/UICC pathologic staging, (b) newly published clinical staging for non
      surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based,
      "HPVpath" staging system that combines features of the primary tumor and nodal
      metastases. RESULTS: A combination of AJCC/UICC pT-classification and pathology
      confirmed metastatic node count (?4 versus ?5) yielded three groups: stages I
      (pT1-T2, ?4 nodes), II (pT1-T2, ?5 nodes; pT3-T4, ?4 nodes), and III (pT3-T4, ?5
      nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%,
      84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked
      prognostic definition. Newly published HPV-specific clinical stagings from non
      surgically managed patients, although prognostic, showed lower precision for this
      surgically managed cohort. CONCLUSIONS: Three loco-regional "HPVpath" stages are
      identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary
      tumor pT-classification and metastatic node count. A workable, pathologic staging
      system is feasible to establish prognosis and guide adjuvant therapy decisions in
      surgically-managed HPV-positive OPSCC.

PMID- 27865366
TI  - Effects of geographic area and socioeconomic status in Taiwan on survival rates
      of head and neck cancer patients after radiotherapy.

PMID- 27865365
TI  - Implications of cancer stem cells in developing therapeutic resistance in oral
      cancer.
AB  - Conventional therapeutics are often frequented with recurrences, refraction and
      regimen resistance in oral cavity cancers which are predominantly manifested by
      cancer stem cells (CSCs). During oncoevolution, cancer cells may undergo
      structural and functional reprogramming wherein they evolve as highly tolerant
      CSC phenotypes with greater survival advantages. The CSCs possess inherent and
      exclusive properties including self-renewal, hierarchical differentiation, and
      tumorigenicity that serve as the basis of chemo-radio-resistance in oral cancer.
      However, the key mechanisms underlying the CSC-mediated therapy resistance need
      to be further elucidated. A spectrum of dysfunctional cellular pathways including
      the developmental signaling, apoptosis, autophagy, cell cycle regulation, DNA
      damage responses and epigenetic regulations protect the CSCs from conventional
      therapies. Moreover, tumor niche shelters CSCs and creates an immunosuppressive
      environment favoring the survival of CSCs. Maintenance of lower redox status,
      epithelial-to-mesenchymal transition (EMT), metabolic reprogramming and altered
      drug responses are the accessory features that aid in the process of chemo-radio
      resistance in oral CSCs. This review deals with the functional and molecular
      basis of cancer cell pluripotency-associated resistance highlighting the abrupt
      fundamental cellular processes; targeting these events may hold a great promise
      in the successful treatment of oral cancer.

PMID- 27865367
TI  - Circulating tumor stem like cells in oral squamous cell carcinoma: An unresolved
      paradox.
AB  - OBJECTIVE: Circulating tumor cells (CTCs) are increasingly gaining importance due
      to their immense potential in enhancing diagnosis, prognosis and response to
      therapy in solid malignancies. Therefore, we aimed to comprehend the molecular
      diversity and critical role of this disseminated tumor population in OSCC.
      METHODOLOGY: CD44+ subpopulation was isolated using immuno-magnetic cell
      separation and their purity was validated using flow cytometry. Characterisation
      of self renewal potential and resistance to chemotherapy was assessed using tumor
      sphere forming and cytotoxicity assay. Gene expression profile of pertinent CSC
      (CD44s, CD44v3, CD44v6) and stemness markers (Bmi1 and Nanog) was carried out in
      CD44+ cells using Real Time PCR. Predominantly expressed markers and their
      association with clinico-pathological conditions were substantiated in 30 OSCC
      patients. RESULT: Flow cytometry analysis depicted a predominant population of
      CD44+CD24-CD45- cells suggesting that circulating tumor cells had a subpopulation
      of CSC like cells in the circulation. These cells demonstrated increased sphere
      forming capability and intrinsic chemo-resistance compared to non-CSC, thus
      indicating the CSC features of self-renewal and chemo-resistance. Additionally,
      CD44+ cells showed significantly increased expression levels of CD44v6 and Nanog
      compared to CD44- cells. Clinically, expression pattern of CD44v6 and Nanog
      correlated with different anatomical subsites, loco-regional aggressiveness of
      the disease and recurrence, thus opening newer avenues that can be explored for
      better prognostic and therapeutic implications. CONCLUSION: This study explored
      the inevitable role of CD44v6 and Nanog as circulating stem like cell markers in
      assessment of loco-regional aggressiveness, detection of relapse and therapeutic
      response and resistance.

PMID- 27865369
TI  - Feasibility of using head and neck CT imaging to assess skeletal muscle mass in
      head and neck cancer patients.
AB  - OBJECTIVES: Patients with head and neck cancer (HNC) have a higher risk of
      malnutrition and sarcopenia, which is associated with adverse clinical outcome.
      As abdominal CT-imaging is often used to detect sarcopenia, such scans are rarely
      available in HNC patients, possibly explaining why no studies investigate the
      effect of sarcopenia in this population. We correlated skeletal muscle mass
      assessed on head and neck CT-scans with abdominal CT-imaging. METHODS: Head and
      neck, and abdominal CT-scans of trauma (n=51) and HNC-patients (n=52) were
      retrospectively analyzed. On the head and neck CT-scans, the paravertebral and
      sternocleidomastoid muscles were delineated. On the abdominal CT-scans, all
      muscles were delineated. Cross-sectional area (CSA) of the muscles at the level
      of the C3 vertebra was compared to CSA at the L3 level using linear regression. A
      multivariate linear regression model was established. RESULTS: HNC-patients had
      significantly lower muscle CSA than trauma patients (37.9 vs. 45.1cm2, p<0.001,
      corrected for sex and age). C3 muscle CSA strongly predicted L3 muscle CSA
      (r=0.785, p<0.001). This correlation was stronger in a multivariate model
      including sex, age and weight (r=0.891, p<0.001). DISCUSSION: Assessment of
      skeletal muscle mass on head and neck CT-scans is feasible and may be an
      alternative to abdominal CT-imaging. This method allows assessment of sarcopenia
      using routinely performed scans without additional imaging or additional patient
      burden. Identifying sarcopenic patients may help in treatment selection, or to
      select HNC patients for physiotherapeutic or nutritional interventions to improve
      their outcome.

PMID- 27865368
TI  - Effect of HPV on head and neck cancer patient survival, by region and tumor site:
      A comparison of 1362 cases across three continents.
AB  - OBJECTIVES: To explore whether HPV-related biomarkers predict oropharyngeal
      squamous cell cancer (OPSCC) survival similarly across different global regions,
      and to explore their prognostic utility among non-oropharyngeal (non-OP) head and
      neck cancers. METHODS: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002
      2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S.
      (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally
      tested for p16INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using
      Cox proportional hazard models. RESULTS: There were 517 OPSCC and 845 non-OP
      HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of
      58yearsandmedian follow-up of 3.1years (IQR=1.4-5.9). Among OPSCC, the risk of
      mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+)
      compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR=0.25, 95%CI=0.18
      0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe,
      and Brazil (each p?0.01) and after adjustment, remained significantly reduced
      (aHR=0.34, 95%CI=0.24-0.49). Among non-OP HNSCC, neither p16 (aHR=0.83,
      95%CI=0.60-1.14), HPV16 DNA (aHR=1.20, 95%CI=0.89-1.63), or p16+/HPV16+
      (aHR=0.59, 95%CI=0.32-1.08) was a significantly predictor of mortality. When
      interaction was tested, the effect of HPV16/p16 was significantly different in
      OPSCC than non-OP HNSCC (p-interaction=0.02). CONCLUSION: HPV-related OPSCCs had
      similar survival benefits across these three regions. Prognostic utility of HPV
      among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely
      done among non-OP HNSCC.

PMID- 27865370
TI  - Hypermethylated ZNF582 and PAX1 are effective biomarkers for detection of oral
      dysplasia and oral cancer.
AB  - OBJECTIVES: This study investigated whether the methylation of ZNF582, PAX1,
      SOX1, NKX6.1, and PTPRR genes in oral scrapings could be used to detect oral
      dysplasia and oral cancer and to predict oral cancer recurrence. MATERIALS AND
      METHODS: Oral scrapings were collected from 65 normal oral mucosa subjects, 107
      oral precancer patients, and 95 oral squamous cell carcinoma patients.
      Methylation levels of the five genes were quantified by real-time methylation
      specific PCR after bisulfite conversion. RESULTS: Among the five tested genes,
      methylated ZNF582 (ZNF582m) and PAX1 (PAX1m) were found to be appropriate
      biomarkers for oral dysplasia and oral cancers. ZNF582m could detect mild
      dysplasia or worse oral lesions with the sensitivity and specificity being 0.85
      and 0.87, respectively. PAX1m performed better in identifying moderate dysplasia
      or worse oral lesions with the sensitivity and specificity being 0.72 and 0.86,
      respectively. Moreover, the methylation levels and positive rates for ZNF582m and
      PAX1m were increased when disease severity increased. Thus, they may be
      applicable as a triage tool for patients with abnormal visual oral examinations.
      After cancer excision, both ZNF582m and PAX1m levels decreased. However, their
      levels increased again at the subsequently recurrent sites in some patients
      approximately 3-4 months before cancer recurrence. Finally, areca-quid chewing
      alone and in combination with cigarette smoking or alcohol drinking were found to
      be correlated with ZNF582 and PAX1 hypermethylation. CONCLUSION: We conclude that
      hypermethylated ZNF582 and PAX1 are effective biomarkers for the detection of
      oral dysplasia and oral cancer and for the prediction of oral cancer recurrence.

PMID- 27865371
TI  - Assessing head and neck cancer patient preferences and expectations: A systematic
      review.
AB  - INTRODUCTION: To enhance the value of care, interventions should aim at improving
      endpoints that matter to patients. The preferences of head and neck cancer
      patients regarding treatment outcomes are therefore a major topic for patient
      centered research. METHODS: A systematic review (PROSPERO number CRD42016035692)
      was conducted by searching electronic databases (Medline, Embase, Cochrane,
      CINAHL) for articles evaluating patient or surrogate preferences in head and neck
      cancer. A qualitative review was performed but no quantitative synthesis.
      RESULTS: Of 817 references retrieved, 20full-text articles were eventually
      included in the qualitative analysis Disease sites included mixed head and neck
      tumor sites, n=9; larynx, n=6; oropharynx/oral cavity, n=5. Overall, patients
      prioritized survival over functional endpoints. However, preferences and utility
      scores varied greatly between patients and healthy subjects, and differences were
      less pronounced with spouses or healthcare providers. Findings from studies of
      laryngeal preservation are consistent and conclude that a subset of patients
      would be willing to compromise a certain amount of survival to avoid
      laryngectomy. On the other hand, studies of patients with oropharyngeal cancer
      are too heterogeneous to draw conclusions about acceptable functional trade-offs
      or priorities, and should be the focus of future research. CONCLUSION: Future
      research surrounding head and neck cancer patients will most likely be clinically
      applicable if the questions are focused on well-defined patient groups and
      treatment options. Gathering reliable and valid quality-of-life data, designing
      patient preference studies that use reliable and generalizable methods, and using
      the results to develop decision aids for shared decision-making strategies are
      recommended going forward.

PMID- 27865372
TI  - Phase II study of panitumumab and paclitaxel as first-line treatment in recurrent
      or metastatic head and neck cancer. TTCC-2009-03/VECTITAX study.
AB  - OBJECTIVE: To evaluate the activity and safety profile of panitumumab in
      combination with paclitaxel in patients with recurrent or metastatic SCCHN.
      MATERIALS AND METHODS: The VECTITAX phase II, open-label, multicenter study
      included patients with confirmed metastatic and/or recurrent SCCHN deemed to be
      untreatable by surgery or radiotherapy and ECOG PS=0-1. All patients received
      paclitaxel (80mg/m2/week) and panitumumab (6mg/kg/2weeks) until disease
      progression or unacceptable toxicity. EQ-5D-3L andvisual analogic scale (VAS)
      were used to evaluate impact on quality of life (QoL). RESULTS: The study
      included 40 patients (ITT population): (median age: 61 years; 87% male). Previous
      treatment: 29 patients (73%) had undergone surgery, 34 (85%) had received prior
      radiotherapy and 23 (58%) prior systemic treatment for locally advanced disease.
      Confirmed response was observed in 19 patients (48%) which was a complete
      response in 15% of patients. Stable disease was observed in 11 patients (28%).
      Disease control rate was 75%. Median progression-free survival was 7.5 months
      (95%CI: 4.9-8.3) and median overall survival 9.9 months (95%CI: 7.9-16.3). Most
      frequent grade 3-4 adverse events were skin rash (25%); asthenia (17%);
      neurotoxicity (15%); hypomagnesemia (10%); neutropenia (10%). Permanent
      discontinuation of panitumumab or paclitaxel due to adverse events was required
      in 10 (25%) and 13 patients (33%), respectively. There was one toxic death due to
      febrile neutropenia. Patient-reported QoL was preserved with no decline of median
      VAS scores. CONCLUSION: Panitumumab and paclitaxel is an active combination,
      providing promising outcomes with preservation of the QoL and a favorable safety
      profile. (EudraCT: 2010-018898-37; NCT01264328).

PMID- 27865373
TI  - Extracapsular spread in head and neck squamous cell carcinoma: A systematic
      review and meta-analysis.
AB  - Extracapsular spread (ECS) is one of the most important prognostic factors in
      head and neck squamous cell carcinoma (HNSCC). However, despite its major
      clinical relevance, there are still a number of important remaining issues
      regarding this condition. Indeed, standardized diagnostic and grading criteria of
      ECS are still lacking. The imaging modality of choice for its diagnosis is a
      matter of debate. Current research looking at the identification of specific
      biomarkers is ongoing. Recent findings demonstrate a direct correlation between
      the level of extension of ECS and a poor prognosis. Accumulating data show that
      ECS does not carry the same adverse features in human papilloma virus (HPV)
      positive oropharyngeal squamous cell carcinoma (OPSCC). New treatment strategies
      based on these factors are currently considered to investigate the possibility of
      diminishing the toxicity of chemo-radiotherapy while maintaining similar
      outcomes. The goal of this article was to provide a systematic review of the
      literature covering all the issues related to ECS. As an additional component of
      the review, meta-analyses were performed on relevant aspects of ECS for which
      previous quantitative data were outdated or not available. The results of these
      meta-analyses confirm the negative impact of ECS on loco-regional recurrence and
      distant metastasis. They also demonstrate the absence of a negative impact of ECS
      in HPV-positive OPSCC.

PMID- 27865374
TI  - Clinical implications of the extent of BRAFV600E alleles in patients with
      papillary thyroid carcinoma.
AB  - OBJECTIVE: There are many conflicting reports about the clinical implications of
      BRAFV600E in papillary thyroid cancer (PTC). We investigated the associations
      between the extent of BRAFV600E alleles and both clinico-pathological features
      and recurrence of PTC. MATERIALS AND METHODS: Carcinoma tissues from 60 patients
      with PTC were genotyped for BRAFV600E using pyrosequencing, and the clinico
      pathological factors and disease outcomes of the patients were examined. The
      associations between the extent of mutant BRAF alleles and both clinico
      pathological parameters and recurrence-free survival (RFS) were analyzed.
      RESULTS: The BRAFV600E mutation was detected in 66.7% (40/60) of our PTC
      patients. When we defined four groups on the basis of the extent of BRAFV600E
      alleles by pyrosequencing-negative (less than 5%), low (5 - less than 15%),
      intermediate (15 - less than 25%), and high (25% or greater)- the four groups
      showed statistically significant differences regarding lymph node (LN) metastasis
      and recurrence (P<0.05). However, age, gender, tumor size, multicentricity,
      capsular invasion, and lymphovascular invasion were not significantly different
      among the groups. The 10-year RFS rates in PTC patients with greater than 25% and
      less than 25% mutated BRAF alleles were 74% and 100%, respectively. This
      difference was significant (P=0.043). CONCLUSIONS: A high extent more than 25% of
      BRAFV600E alleles may be associated with disease outcome in PTC patients. We need
      more data to verify a hypothesis that the extent of BRAF mutations may be
      clinically informative in the management of PTC, such as by tailoring proper
      surgical and radioactive iodine treatments and determining appropriate management
      during follow-up.

PMID- 27865375
TI  - Optimize the cycle of neoadjuvant chemotherapy for locoregionally advanced
      nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: A
      propensity score matching analysis.
AB  - OBJECTIVES: The aim of this study is to optimize the cycle for patients with
      locoregionally advanced nasopharyngeal carcinoma (NPC) receiving neoadjuvant
      chemotherapy (NCT) in the era of intensity-modulated radiotherapy (IMRT).
      MATERIALS AND METHODS: Data on 569 locoregionally advanced NPC patients treated
      with IMRT were retrospectively reviewed. Propensity score matching (PSM) method
      was adopted to balance prognostic factors and match patients. Survival outcomes
      of matched patients between different NCT cycle groups were compared. RESULTS:
      The median cycle of NCT was 2 (range, 2-4 cycles) for the whole cohort, and
      patients were therefore stratified as low cycle (=2) and high cycle (>2) groups.
      In total, 247 pairs of NPC patients were selected by PSM. Univariate analysis
      found no significantly prognostic difference between the low cycle and high cycle
      groups, and multivariate analysis did not establish NCT cycle as an independent
      factor. However, stratified analysis revealed patients in the low cycle group had
      better OS than those of patients in the high cycle group (92.4% vs. 80.8%,
      P=0.029), and NCT was identified as an independent prognostic factor for OS in
      patients with N2-3 category (HR, 2.252; 95% CI, 1.024-4.953; P=0.043).
      CONCLUSION: Two cycles of NCT may be enough and additional more cycles are not
      associated with improved survival outcomes for patients with locoregionally
      advanced NPC in the era of IMRT.

PMID- 27865376
TI  - Free flap outcome of salvage surgery compared to primary surgery for head and
      neck defects: A propensity score analysis.
AB  - OBJECTIVES: To compare free flap outcomes for head and neck defects between
      primary surgery and salvage surgery and identify factors affecting the outcomes
      in the two settings. METHODS: A total of 225 patients (primary group, n=56;
      salvage group, n=169) were retrospectively identified. The salvage group was
      previously treated with radiotherapy, chemoradiation, surgery, or any combination
      of these treatments. Clinical data were retrieved and analyzed between the two
      groups to compare the incidence and contributing factors of flap-related
      complications and flap failure. A propensity score analysis with matching T
      stage, defect, and flap types was also performed for unbiased comparisons.
      RESULTS: Flap-related complication rate was 22.2% in all patients. The salvage
      group showed higher rates of wound dehiscence than the primary group (3.6% in
      primary vs. 13.0% in salvage; p=0.04). Flap failures occurred in 10 patients
      (4.4%), including 3 (5.4%) in the primary group and 7 (4.1%) in the salvage group
      (p=0.71). Multivariate analysis showed no critical factor that influenced the
      occurrence of flap-related complications or flap failure, including surgery type
      (primary or salvage). In propensity score analysis, incidences and types of flap
      related complications and flap failure were not statistically different between
      the two groups (primary and salvage). CONCLUSIONS: Free flap reconstruction is a
      safe and reliable method to restore the ablative defects in previously irradiated
      or operated head and neck defects.

PMID- 27865377
TI  - Risk factors for radiation failure in early-stage glottic carcinoma: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Radiotherapy is one of the main treatment modalities for early-stage
      glottic carcinoma. Unfortunately, local failure may occur in a group of cases
      with T1-T2 glottic carcinoma. This meta-analysis sought to determine risk factors
      for radiation failure in patients with early-stage glottic carcinoma. METHODS: A
      systematic and comprehensive search was performed for related studies published
      between 1995 and 2014. The primary end-point was 5-year local control. Data
      extraction and analysis were performed using the software STATA/SE 13.1 for
      Windows. RESULTS: Twenty-seven studies were eligible. A higher risk of radiation
      failure was demonstrated in male patients [relative risk (RR): 0.927, p<0.001]
      and those with low hemoglobin level (RR: 0.891, p<0.001) with a high agreement
      between studies (I-squared=0.0%). Moreover, T2 tumors (RR: 0.795, p<0.001),
      tumors with anterior commissure involvement (RR: 0.904, p<0.001), tobacco use
      during/after therapy (RR: 0.824, p<0.001), and "bulky" tumors (RR: 1.270,
      p<0.001] or tumors bigger in size (RR: 1.332, p<0.001]. Poorly differentiated
      tumors had a questionable risk of local failure, although a moderate to high
      interstudy heterogeneity was determined. A statistically significant contribution
      was not detected for age, presence of comorbidity, alcohol use or subglottic
      extension. CONCLUSION: This is the first meta-analysis which assessed the
      potential risk factors for radiation failure in patients with early-stage glottic
      carcinoma. Gender and pretreatment hemoglobin level are major influential factors
      associated with radiation failure in patients with early-stage glottic carcinoma.
      However, prospective, randomized clinical trials may permit better stratification
      of their relative contributions, and those who may benefit more from upfront
      surgery.

PMID- 27865378
TI  - Development of immune-biomarkers of pulmonary tuberculosis in a rabbit model.
AB  - Tuberculosis (TB) causes extensive morbidity and mortality worldwide with
      approximately 10 million new cases of active disease emerging mostly from a pool
      of two billion individuals latently infected with Mycobacterium tuberculosis (M.
      tb) every year. The underlying host immune responses that drive M. tb infection
      to active disease or latency are not well understood. We propose that
      identification and characterization of host immune biomarkers will be helpful to
      better understand the mechanisms that drive this process, and may, in addition,
      lead to the development of better diagnostic tools for TB. We have previously
      reported the profiles of plasma immune biomarkers in pulmonary TB patients in
      endemic countries, and in M. tb-infected nonhuman primates. However, biomarker
      profiling for a cost-effective and user-friendly animal model relevant to human
      disease, such as rabbit, has not been developed. One challenge in the analysis of
      circulating cytokines/chemokines for rabbit model of TB is the limited
      availability of validated immune-reagents. Here we report the use of a
      commercially available multiplex microbead human cytokine/chemokine panels as
      development platform for rabbit immune reagents. The results demonstrate their
      utility to determine circulating analytes and define their profiles related to TB
      in the rabbit model. In addition, we report the profiles of circulating anti-M.
      tb antibodies in the plasma of rabbits with active pulmonary TB. These studies
      show that the pattern of expression of circulating immune biomarkers correlate
      with TB pathology in rabbits, and are similar to those defined in pulmonary TB
      patients.

PMID- 27865380
TI  - Highly sensitive sequence specific qPCR detection of Mycobacterium tuberculosis
      complex in respiratory specimens.
AB  - Nucleic acid amplification tests for Mycobacterium tuberculosis (MTB) detection
      from sputum are highly sensitive and specific with smear microscopy positive
      specimens, but their sensitivity with smear-negative/culture-positive specimens
      is much lower; therefore, these tests cannot rule out a tuberculosis diagnosis.
      Co-extraction of PCR inhibitors may be a cause of decreased test sensitivity.
      Here the design and early validation of a MTB screening assay with sample
      preparation and qPCR methods designed to specifically address this diagnostic gap
      is reported. First, human genomic DNA is identified as a significant qPCR
      inhibitor. To circumvent this problem, a novel, streamlined sample preparation
      method utilizing detergent and proteolysis to thin the sputum and DNA sequence
      specific MTB DNA isolation was developed. Additionally, a multiplexed qPCR assay
      targeting two MTB complex-specific loci: the potentially multi-copy IS6110 and
      the single-copy senX3-regX3, combined with the cotJC gene from Bacillus
      atrophaeus spores amplified as a process control was developed. The limit of
      detection of the test was estimated to be 20 cfu/ml which is significantly lower
      than the Xpert(r) MTB/RIF assay. In a preliminary field study of 60 de-identified
      blinded sputa, a test sensitivity of 96% and specificity of 100% was observed
      when compared to the Xpert(r) MTB/RIF assay.

PMID- 27865382
TI  - BCG infection in mice is promoted by naive mesenchymal stromal cells (MSC) and
      suppressed by poly(A:U)-conditioned MSC.
AB  - Mesenchymal stromal cells (MSC) transplantation is an actively studied
      therapeutic approach used in regenerative medicine and in the field of control of
      immunoinflammatory response. Conditioning of MSC in culture can form their
      predominantly pro- or anti-inflammatory phenotypes. We demonstrated that
      poly(A:U)-conditioning of bone marrow-derived mouse MSC induced predominantly pro
      inflammatory phenotype. The effects of administration of naive MSC (nMSC) or
      conditioned MSC (cMSC) on the course of mycobacterial infection were studied.
      BALB/c mice infected i.p. with 5 * 106 M. bovis BCG were successively injected
      i.v. with 0.75 * 106 of nMSC or cMSC in 11 and 12.5 weeks after infection and
      sacrificed at the week 14. Histological and bacteriological examination of BCG
      infected animals revealed low bacterial loads in liver, lungs and spleen; the
      bacterial load in spleen was higher than in other organs. Treatment with nMSC
      induced 3-fold increase of the number of bacteria in spleen granulomas, while
      cMSC decreased significantly the number of bacteria in BCG-positive granulomas.
      Analysis of preparations of organ homogenates by luminescent microscopy, MGIT
      cultures and CFU count on Lowenstein-Jensen medium revealed that nMSC promoted
      mycobacterial growth whereas cMSC suppressed mycobacterial growth significantly.
      We concluded that MSC therapy can be effective in mycobacterial infection, but
      only in a case of appropriate conditioning of the cells.

PMID- 27865381
TI  - The impact of Bacille Calmette-Guerin shortage on immunisation practice and
      policies in Europe - A Paediatric Tuberculosis Network European Trials Group
      (ptbnet) survey.
AB  - BACKGROUND: Recent reports indicate an ongoing BCG shortage that may influence
      immunisation practice. This study aimed to determine current availability of BCG
      vaccine across Europe, and implications on immunisation practices and policies in
      Europe. METHODS: Web-based survey among Paediatric Tuberculosis Network European
      Trials Group (ptbnet) members, between May and October 2015. RESULTS: Twenty
      individuals from 13 European countries participated. Ongoing shortages were
      reported in eight countries routinely using BCG (8/11, 73%). As a consequence of
      the shortage, BCG was not given as completely unavailable in some countries (2/8,
      25%), was given only whenever available (1/8, 13%), or only in certain regions of
      the country (1/8, 13%). Strategies reported to reduce loss of immunisation were
      administration to selected high-risk individuals (2/8, 25%), or cohorting
      vaccinees on specific days to maximise the use of multi-dose vials (3/8, 38%).
      Authorities in two countries each were considering a change of
      manufacturer/supplier (2/8, 25%). CONCLUSIONS: The BCG shortage in Europe leads
      to significant changes in immunisation policies including changes of BCG vaccine
      strain and manufacturer. In addition, infants and children eligible for
      immunisation are at risk of not receiving BCG. To ensure necessary BCG
      immunisations, collaboration between national health agencies and vaccine
      manufacturers is crucial.

PMID- 27865383
TI  - Analytical and clinical performance characteristics of the Abbott RealTime MTB
      RIF/INH Resistance, an assay for the detection of rifampicin and isoniazid
      resistant Mycobacterium tuberculosis in pulmonary specimens.
AB  - Clinical management of drug-resistant tuberculosis patients continues to present
      significant challenges to global health. To tackle these challenges, the Abbott
      RealTime MTB RIF/INH Resistance assay was developed to accelerate the diagnosis
      of rifampicin and/or isoniazid resistant tuberculosis to within a day. This
      article summarizes the performance of the Abbott RealTime MTB RIF/INH Resistance
      assay; including reliability, analytical sensitivity, and clinical
      sensitivity/specificity as compared to Cepheid GeneXpert MTB/RIF version 1.0 and
      Hain MTBDRplus version 2.0. The limit of detection (LOD) of the Abbott RealTime
      MTB RIF/INH Resistance assay was determined to be 32 colony forming
      units/milliliter (cfu/mL) using the Mycobacterium tuberculosis (MTB) strain H37Rv
      cell line. For rifampicin resistance detection, the Abbott RealTime MTB RIF/INH
      Resistance assay demonstrated statistically equivalent clinical sensitivity and
      specificity as compared to Cepheid GeneXpert MTB/RIF. For isoniazid resistance
      detection, the assay demonstrated statistically equivalent clinical sensitivity
      and specificity as compared to Hain MTBDRplus. The performance data presented
      herein demonstrate that the Abbott RealTime MTB RIF/INH Resistance assay is a
      sensitive, robust, and reliable test for realtime simultaneous detection of first
      line anti-tuberculosis antibiotics rifampicin and isoniazid in patient specimens.

PMID- 27865379
TI  - Antibodies and tuberculosis.
AB  - Tuberculosis (TB) remains a major public health problem internationally, causing
      9.6 million new cases and 1.5 million deaths worldwide in 2014. The Bacillus
      Calmette-Guerin vaccine is the only licensed vaccine against TB, but its
      protective effect does not extend to controlling the development of infectious
      pulmonary disease in adults. The development of a more effective vaccine against
      TB is therefore a pressing need for global health. Although it is established
      that cell-mediated immunity is necessary for the control of latent infection, the
      presupposition that such immunity is sufficient for vaccine-induced protection
      has recently been challenged. A greater understanding of protective immunity
      against TB is required to guide future vaccine strategies against TB. In contrast
      to cell-mediated immunity, the human antibody response against M.tb is
      conventionally thought to exert little immune control over the course of
      infection. Humoral responses are prominent during active TB disease, and have
      even been postulated to contribute to immunopathology. However, there is evidence
      to suggest that specific antibodies may limit the dissemination of M.tb, and
      potentially also play a role in prevention of infection via mucosal immunity.
      Further, antibodies are now understood to confer protection against a range of
      intracellular pathogens by modulating immunity via Fc-receptor mediated
      phagocytosis. In this review, we will explore the evidence that antibody-mediated
      immunity could be reconsidered in the search for new vaccine strategies against
      TB.

PMID- 27865384
TI  - The in vitro mechanisms of isoniazid and ethionamide resistance poorly reflect
      those in vivo in Mycobacterium tuberculosis.

PMID- 27865385
TI  - The characteristic profiles of PD-1 and PD-L1 expressions and dynamic changes
      during treatment in active tuberculosis.
AB  - PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in
      tuberculosis is controversial because of lack of congruence between clinical
      study and animal model. To investigate the immunological pathogenesis mechanisms
      of tuberculosis and to develop the immune therapy target essential for
      controlling tuberculosis, here we explored the expression characteristics and
      dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We
      enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9
      healthy donors (HD). The expressions of PD-1 and PD-L1 on CD4+T cells increased
      significantly in ATB patients than HD. ATB patients had a higher proportion of
      regulatory T cells (Treg, CD4+CD25 + Foxp3+) than HD. The expressions of PD-1 and
      PD-L1 increased remarkably on CD4+T cell subsets, including Treg cells, Tresp
      (CD4+CD25-) cells and Teff (CD4+CD25 + Foxp3-) cells. Finally, clinical
      improvement following effective anti-TB therapy is correlated with significantly
      decreased expression of PD-1 in Tresp and Teff cells, but not in Treg cells.
      Thus, expression profiles of PD-1 in T cell subpopulations may be used as a
      candidate to predict the clinical efficacy of anti-tuberculosis therapy.
      Modulation of PD-1/PD-L1 pathway in CD4 subsets may offer an immunotherapy target
      for the control of tuberculosis.

PMID- 27865386
TI  - Factors associated with anti-TB drug-induced hepatotoxicity and genetic
      polymorphisms in indigenous and non-indigenous populations in Brazil.
AB  - Anti-tuberculosis (TB) drugs are responsible for the occurrence of several
      adverse drug reactions (ADRs), including hepatotoxicity. The aim was to estimate
      the incidence of hepatotoxicity and its association with genetic polymorphisms
      and clinical-epidemiological factors by comparing indigenous and non-indigenous
      TB patients. We investigated clinical-epidemiological variables, serum levels of
      liver enzymes and NAT2, CYP2E1 and GSTM1 polymorphisms. A non-conditional
      logistic regression was used to identify the factors associated with
      hepatotoxicity. Odds ratios were used as the association measures. The incidence
      of hepatotoxicity was 19.7% for all patients. The risk of hepatotoxicity was
      almost four times higher in indigenous patients, comparing to non-indigenous. We
      identified a new nonsynonymous single nucleotide polymorphism of NAT2 in
      indigenous patients. In total, 54.6% of the patients expressed a slow acetylation
      phenotype profile. The frequency of the null genotype of GSTM1 was higher in non
      indigenous patients (p = 0.002), whereas no significant differences in relation
      to polymorphisms of CYP2E1 were observed between the groups. Hepatotoxicity was
      associated with patients older than 60 and indigenous (OR = 26.0; 95%CI:3.1
      217.6; OR = 3.8; 95%CI:1.3-11.1, respectively). Furthermore, hepatotoxicity was
      associated with a slow acetylation profile in indigenous patients (OR = 10.7;
      95%CI:1.2-97.2). Our findings suggest that there are distinct acetylation
      profiles in the Brazilian population, emphasizing the importance of
      pharmacogenetic analyses for achieving personalized therapeutic schemes and
      better outcomes.

PMID- 27865387
TI  - MicroRNA expression signatures in lungs of mice infected with Mycobacterium
      tuberculosis.
AB  - Tuberculosis (TB) is a major public health concern worldwide; however the factors
      that account for resistance or susceptibility to disease are not completely
      understood. Although some studies suggest that the differential expression of
      miRNAs in peripheral blood of TB patients could be useful as biomarkers of active
      disease, their involvement during the inflammatory process in lungs of infected
      individuals is unknown. Here, we evaluated the global expression of miRNAs in the
      lungs of mice experimentally infected with Mycobacterium tuberculosis on 30 and
      60 days post-infection. We observed that several miRNAs were differentially
      expressed compared to uninfected mice. Furthermore, we verified that the
      expression of miR-135b, miR-21, miR-155, miR-146a, and miR-146b was significantly
      altered in distinct leukocyte subsets isolated from lungs of infected mice, while
      genes potentially targeted by those miRNAs were associated with a diversity of
      immune related molecular pathways. Importantly, we validated the inhibition of
      Pellino 1 expression by miR-135b in vitro. Overall, this study contributes to the
      understanding of the dynamics of miRNA expression in lungs during experimental TB
      and adds further perspectives into the role of miRNAs on the regulation of immune
      processes such as leukocyte activation.

PMID- 27865388
TI  - Quick and cheap MIRU-VNTR typing of Mycobacterium tuberculosis species complex
      using duplex PCR.
AB  - While minisatellites are usually typed using capillary sequencers or qiaplex
      systems in developed countries, many low-resource regions cannot afford it. We
      propose an optimized agarose gel electrophoresis method to genotype Mycobacterium
      tuberculosis species complex minisatellites in their standardized format (24 MIRU
      VNTR). It is based on duplex PCRs combining VNTR loci harboring distinct amplicon
      sizes whatever the repetition number of each locus. This method performs well
      both on DNA extracts of good quality and on thermolysates while reducing workload
      and reagents costs.

PMID- 27865389
TI  - Mycobacterium indicus pranii as a booster vaccine enhances BCG induced immunity
      and confers higher protection in animal models of tuberculosis.
AB  - BCG, the only approved vaccine protects against severe form of childhood
      tuberculosis but its protective efficacy wanes in adolescence. BCG has reduced
      the incidence of infant TB considerably in endemic areas; therefore prime-boost
      strategy is the most realistic measure for control of tuberculosis in near
      future. Mycobacterium indicus pranii (MIP) shares significant antigenic
      repertoire with Mtb and BCG and has been shown to impart significant protection
      in animal models of tuberculosis. In this study, MIP was given as a booster to
      BCG vaccine which enhanced the BCG mediated immune response, resulting in higher
      protection. MIP booster via aerosol route was found to be more effective in
      protection than subcutaneous route of booster immunization. Pro-inflammatory
      cytokines like IFN-gamma, IL-12 and IL-17 were induced at higher level in
      infected lungs of 'BCG-MIP' group both at mRNA expression level and in secretory
      form when compared with 'only BCG' group. BCG-MIP groups had increased frequency
      of multifunctional T cells with high MFI for IFN-gamma and TNF-alpha in Mtb
      infected mice. Our data demonstrate for the first time, potential application of
      MIP as a booster to BCG vaccine for efficient protection against tuberculosis.
      This could be very cost effective strategy for efficient control of tuberculosis.

PMID- 27865391
TI  - Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co
      morbidity upon standard tuberculosis treatment.
AB  - Type 2 diabetes mellitus (DM) is a major risk factor for the development of
      active pulmonary tuberculosis (PTB), with development of DM pandemic in countries
      where tuberculosis (TB) is also endemic. However, the effect of anti-TB treatment
      on the changes in dentritic cell (DC) and monocyte subset phenotype in TB-DM co
      morbidity is not well understood. In this study, we characterized the frequency
      of DC and monocyte subsets in individuals with PTB with (PTB-DM) or without
      coincident diabetes mellitus (PTB-NDM) before, during and after completion of
      anti-TB treatment. PTB-DM is characterized by diminished frequencies of
      plasmacytoid and myeloid DCs and classical and intermediate monocytes at baseline
      and 2 months of anti-TB treatment but not following 6 months of treatment
      completion in comparison to PTB-NDM. DC and monocyte subsets exhibit significant
      but borderline correlation with fasting blood glucose and glycated hemoglobin
      levels. Finally, while minor changes in the DC and monocyte compartment were
      observed at 2 months of treatment, significantly increased frequencies of
      plasmacytoid and myeloid DCs and classical and intermediate monocytes were
      observed at the successful completion of anti-TB treatment. Our data show that
      coincident diabetes alters the frequencies of innate subset distribution of DC
      and monocytes in TB-DM co-morbidity and suggests that most of these changes are
      reversible following anti-TB therapy.

PMID- 27865392
TI  - Mycobacterium indicus pranii (MIP) mediated host protective intracellular
      mechanisms against tuberculosis infection: Involvement of TLR-4 mediated
      signaling.
AB  - Mycobacterium tuberculosis infection inflicts the disease Tuberculosis (TB),
      which is fatal if left untreated. During M. tuberculosis infection, the pathogen
      modulates TLR-4 receptor down-stream signaling, indicating the possible
      involvement of TLR-4 in the regulation of the host immune response. Mycobacterium
      indicus pranii (MIP) possesses immuno-modulatory properties which induces the pro
      inflammatory responses via induction of TLR-4-mediated signaling. Here, we
      observed the immunomodulatory properties of MIP against tuberculosis infection.
      We have studied the detailed signaling mechanisms employed by MIP in order to
      restore the host immune response against the in vitro tuberculosis infection. We
      observed that in infected macrophages MIP treatment significantly increased the
      TLR-4 expression as well as activation of its downstream signaling, facilitating
      the activation of P38 MAP kinase. MIP treatment was able to activate NF-kappaB
      via involvement of TLR-4 signaling leading to the enhanced pro-inflammatory
      cytokine and NO generation in the infected macrophages and generation of
      protective immune response. Therefore, we may suggest that, TLR4 may represent a
      novel therapeutic target for the activation of the innate immune response during
      Tuberculosis infection.

PMID- 27865390
TI  - Alternative BCG delivery strategies improve protection against Mycobacterium
      tuberculosis in non-human primates: Protection associated with mycobacterial
      antigen-specific CD4 effector memory T-cell populations.
AB  - Intradermal (ID) BCG injection provides incomplete protection against TB in
      humans and experimental models. Alternative BCG vaccination strategies may
      improve protection in model species, including rhesus macaques. This study
      compares the immunogenicity and efficacy of BCG administered by ID and
      intravenous (IV) injection, or as an intratracheal mucosal boost (ID + IT),
      against aerosol challenge with Mycobacterium tuberculosis Erdman strain. Disease
      pathology was significantly reduced, and survival improved, by each BCG
      vaccination strategy, relative to unvaccinated animals. However, IV induced
      protection surpassed that achieved by all other routes, providing an opportunity
      to explore protective immunological mechanisms using antigen-specific IFN-gamma
      ELISpot and polychromatic flow cytometry assays. IFN-gamma spot forming units and
      multifunctional CD4 T-cell frequencies increased significantly following each
      vaccination regimen and were greatest following IV immunisation. Vaccine-induced
      multifunctional CD4 T-cells producing IFN-gamma and TNF-alpha were associated
      with reduced disease pathology following subsequent M.tb challenge; however, high
      frequencies of this population following M.tb infection correlated with increased
      pathology. Cytokine producing T-cells primarily occupied the CD4 transitional
      effector memory phenotype, implicating this population as central to the
      mycobacterial response, potentially contributing to the stringent control
      observed in IV vaccinated animals. This study demonstrates the protective
      efficacy of IV BCG vaccination in rhesus macaques, offering a valuable tool for
      the interrogation of immunological mechanisms and potential correlates of
      protection.

PMID- 27865394
TI  - Recent developments in genomics, bioinformatics and drug discovery to combat
      emerging drug-resistant tuberculosis.
AB  - Emergence of drug-resistant tuberculosis (DR-TB) is a big challenge in TB
      control. The delay in diagnosis of DR-TB leads to its increased transmission, and
      therefore prevalence. Recent developments in genomics have enabled whole genome
      sequencing (WGS) of Mycobacterium tuberculosis (M. tuberculosis) from 3-day-old
      liquid culture and directly from uncultured sputa, while new bioinformatics tools
      facilitate to determine DR mutations rapidly from the resulting sequences. The
      present drug discovery and development pipeline is filled with candidate drugs
      which have shown efficacy against DR-TB. Furthermore, some of the FDA-approved
      drugs are being evaluated for repurposing, and this approach appears promising as
      several drugs are reported to enhance efficacy of the standard TB drugs, reduce
      drug tolerance, or modulate the host immune response to control the growth of
      intracellular M. tuberculosis. Recent developments in genomics and bioinformatics
      along with new drug discovery collectively have the potential to result in
      synergistic impact leading to the development of a rapid protocol to determine
      the drug resistance profile of the infecting strain so as to provide personalized
      medicine. Hence, in this review, we discuss recent developments in WGS,
      bioinformatics and drug discovery to perceive how they would transform the
      management of tuberculosis in a timely manner.

PMID- 27865395
TI  - Innovative Tuberculosis Symposium held during Cuba Salud 2015.
AB  - The fourth Tuberculosis (TB) Symposium, held during the Cuba Salud 2015
      International Convention, highlighted advancements in research on TB and
      Mycobacterium tuberculosis (Mtb) by interdisciplinary teams from academic and
      federal institutions in Cuba, Colombia, Mexico, and the Dominican Republic.
      Delegates focused on the targets presented in the World Health Organization End
      TB Strategy for 2016-2035 and elaborated on four primary themes: 1) attention to
      vulnerable populations such as immunocompromised individuals, health care
      workers, and residents of long-term institutions such as prisons and nursing
      homes; 2) identification of active and latent TB cases through contact
      investigations; 3) spread and control of drug-resistant Mtb strains; and 4)
      advancements in the development of novel vaccines or "booster" immunizations.
      This international TB forum served as a platform for experts in diverse
      disciplines in these Latin American countries to discuss challenges faced by TB
      research and control programs, proposing novel research initiatives and promoting
      collaborative teamwork strategies for TB elimination. In solidarity,
      collaborative efforts in TB control require identification of symptomatic
      individuals, rapid diagnostic testing for TB, drug susceptibility assays on Mtb
      strains, and management that provide universal and gratuitous access to directly
      observed short-course therapy.

PMID- 27865393
TI  - Selective reduction of IFN-gamma single positive mycobacteria-specific CD4+ T
      cells in HIV-1 infected individuals with latent tuberculosis infection.
AB  - HIV-1 is recognized to increase the risk for tuberculosis even before CD4+ T cell
      deficiency is profound. To better understand how HIV-1 alters immunity to latent
      tuberculosis, we compared the magnitude and functional profile of mycobacteria
      specific CD4+ T cells between HIV-uninfected and HIV-infected individuals, using
      flow cytometry. In HIV-1 infection, IFN-gamma single positive mycobacteria
      specific CD4+ T cells were decreased, while the frequency of polyfunctional cells
      (IFN-gamma+IL-2+TNF-alpha+) remained unchanged. Moreover, the proportion of IFN
      gamma single positive cells correlated inversely with viral replication. Our
      results suggest that HIV-1 affects mycobacteria-specific cells differentially,
      depending on their functional capacity.

PMID- 27865398
TI  - Primate models of tuberculosis. Faith-based or evidence-based science.

PMID- 27865396
TI  - Mycobacterium smegmatis proteoliposome induce protection in a murine progressive
      pulmonary tuberculosis model.
AB  - Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB
      vaccine, BCG, is not fully protective against the adult form of the disease and
      is unable to prevent its transmission although it is still useful against severe
      childhood TB. Hence, the search for new vaccines is of great interest. In a
      previous study, we have shown that proteoliposomes obtained from Mycobacterium
      smegmatis (PLMs) induced cross reactive humoral and cellular response against
      Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the
      protective capability of PLMs, a murine model of progressive pulmonary TB was
      used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL
      respectively) showed protection compared to non-immunized animals. Mice immunized
      with PLMsAL induced similar protection as that of BCG. Animals immunized with
      BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage
      of pneumonic area/lung) compared to non-immunized animals, with a more prominent
      effect in BCG vaccinated mice. The protective effect of the administration of
      PLMs in mice supports its future evaluation as experimental vaccine candidate
      against Mtb.

PMID- 27865397
TI  - Transmission of multi-drug resistant tuberculosis in Mongolia is driven by
      Beijing strains of Mycobacterium tuberculosis resistant to all first-line drugs.
AB  - BACKGROUND: Mongolia has high and rising rates of multi-drug resistant
      tuberculosis (MDR-TB). Spatio-temporal and programmatic evidence suggests a major
      contribution from MDR-TB transmission, but genotypic evidence has not been
      assessed. METHODS: All MDR-TB cases identified during 2012 were examined.
      Demographic and bacteriological data were obtained from the National Tuberculosis
      Reference Laboratory. Isolates of Mycobacterium tuberculosis from culture
      confirmed category 1 treatment failures were genotyped using 24-loci
      mycobacterium interspersed repetitive unit (MIRU-24) analysis. RESULTS: Of the
      210 MDR-TB cases identified, 115 (54.8%) were treatment failures (34.8% category
      1; 20.0% category 2). Streptomycin resistance was present in 156 (74.3%) cases;
      including 55/73 (75.3%) category 1 treatment failures who had never been exposed
      to streptomycin. Among category 1 treatment failures, Beijing lineage strains
      predominated (88.0%; 59/67 of genotyped isolates). MIRU-24 clustering was
      documented in 62.7% (42/67) of strains; 55.2% (37/67) remained clustered when
      drug susceptibility test results were considered. In total 59.5% (25/42) of
      clustered strains were Beijing lineage and demonstrated in-vitro resistance to
      all first-line drugs tested. CONCLUSION: The MDR-TB epidemic in Mongolia appears
      to be driven by primary transmission of Beijing lineage strains resistant to all
      first-line drugs. Enhanced infection control strategies together with early MDR
      TB case detection and appropriate treatment are necessary to limit escalation of
      the MDR-TB epidemic.

PMID- 27865399
TI  - High body mass index is associated with heightened systemic and mycobacterial
      antigen - Specific pro-inflammatory cytokines in latent tuberculosis.
AB  - High body mass index (HBMI) has been shown to be protective against active
      tuberculosis (TB), although the biological mechanism underlying this protection
      is poorly understood. The immunological association between HBMI and latent TB
      has never been examined. In order to study the association of HBMI with latent
      TB, we examined the circulating and TB- antigen or mitogen stimulated levels of a
      large panel of cytokines in individuals with latent TB (LTB) and high or normal
      body mass index (HBMI or NBMI). HBMI is characterized by heightened circulating
      levels of pro-inflammatory (IFNgamma, TNFalpha, IL-22, IL-1alpha, IL-12 and GM
      CSF) cytokines but decreased circulating levels of anti-inflammatory cytokines
      (IL-4, IL-5 and TGFbeta). This systemic cytokine profile is associated with
      elevated TB-antigen and mitogen stimulated levels of IFNgamma, TNFalpha, IL-2 and
      IL-1alpha and diminished levels of IL-10 and TGFbeta. In addition, we also
      observed a positive correlation between the circulating levels of IFNgamma,
      TNFalpha, IL-22, IL-1alpha with BMI and a negative correlation between the
      circulating levels of IL-10, TGFbeta and BMI. Our data, therefore, suggest the
      modulation of protective and regulatory cytokines might underlie the protective
      effect of HBMI against the development of active TB.

PMID- 27865400
TI  - New Mycobacterium tuberculosis LAM sublineage with geographical specificity for
      the Old World revealed by phylogenetical and Bayesian analyses.
AB  - We recently showed that the Mycobacterium tuberculosis sublineage LAM9 could be
      subdivided as two distinct subpopulations - each reflecting its unique
      biogeographical structure and evolutionary history. We subsequently attempted to
      verify if this genetic structuration could be traced in an enlarged global
      sample. For this purpose, we analyzed global evolutionary relationships of LAM
      strains in a large dataset (n = 1923 isolates from 35 countries worldwide) with
      concomitant spoligotyping and MIRU-VNTR data, followed by a deeper analysis of
      LAM9 sublineage (n = 851 isolates). Based on a combination of phylogenetical
      analysis and Bayesian statistics, a total of three different clusters,
      tentatively named LAM9C1, C2 and C3 were described in this dataset. Closer
      inspection of the phylogenetic tree with concomitant data on origin of isolates
      with genetic clusterization revealed LAM9C3 being the most tightly knit group
      exclusively found in the Old World as opposed to LAM9C2 being a loosely-knit
      group without any phylogeographical specificity; while LAM9C1 appeared with a
      majority of strains being well-clustered despite some isolates that intermixed
      with unrelated LAM clusters. Subsequently, we hereby describe a new M.
      tuberculosis LAM sublineage named LAM9C3 with phylogeographical specificity for
      the Old World. These findings open new perspectives to study respective migration
      histories and adaptation to human hosts of specific M. tuberculosis clones during
      the exploration and conquest of the New World. We therefore plan to reevaluate
      the nomenclature and evolutionary history of various LAM sublineages using Whole
      Genome Sequencing (WGS).

PMID- 27865401
TI  - Relating annual migration from high tuberculosis burden country of origin to
      changes in foreign-born tuberculosis notification rates in low-medium incidence
      European countries.
AB  - The level of immigration from high tuberculosis (TB) burden countries (HBCs)
      which impacts on the foreign-born TB notification rate is largely unknown. In
      this work, we performed a cross-sectional analysis of epidemiological data from
      2000 to 2013 from nine European countries: Austria, Denmark, Finland, Hungary,
      Netherlands, Norway, Spain, Sweden, and the United Kingdom. Crude notification
      rates were calculated for foreign- and native-born populations and a multiple
      linear regression model predicting notification rates with HBC population data
      was generated. From 2000 to 2013, the population percentage with a foreign
      birthplace increased on average each year in all nine countries, ranging from
      +0.11%/year in the Netherlands to +0.66%/year in Spain. An annual increase in HBC
      migrants above +0.43% per year (95% Confidence Interval: 0.24%-0.63%)
      corresponded with higher TB notification rates in the foreign-born population of
      the countries analyzed. This indicates that migration from HBCs can exert a
      measurable effect on the foreign-born TB notification rate. However, an increase
      in the foreign-born TB notification rate coincided with an average annual rise in
      national TB notification rates only in countries, Norway (+3.85%/year) and Sweden
      (+2.64%/year), which have a high proportion (>80%) of TB cases that are foreign
      born.

PMID- 27865402
TI  - Some proteins of M. tuberculosis that localise to the nucleus of THP-1-derived
      macrophages.
AB  - Host-pathogen dialectics in tuberculosis (TB) via DNA-protein interactions are
      emerging. We investigated whether proteins produced by Mycobacterium tuberculosis
      (Mtb) could translocate to the host nucleus. Using lysates of nuclei purified
      from Mtb-infected THP-1-derived macrophages, we identified at least 15 proteins
      of Mtb-origin by electrophoretic and chromatographic separation and mass
      spectrometry. Western blotting confirmed time-dependent accumulation of Mtb EF
      Tu, GroEL, GroES and MtrA in the host nucleus. MtrA could pull down at least 16
      host proteins. Mtb proteins may have moonlighting functions that affect host gene
      expression.

PMID- 27865403
TI  - Propidium monoazide and Xpert MTB/RIF to quantify Mycobacterium tuberculosis
      cells.
AB  - Propidium monoazide (PMA) penetrates non-viable cells with compromised membranes.
      PMA has been proposed to improve the specificity of Xpert MTB/RIF (Xpert) for the
      detection of viable Mycobacterium tuberculosis. This study assessed the effect of
      PMA on Xpert cycle thresholds (CT) of M. tuberculosis made non-viable under
      antibiotic pressure. In vitro, we measured the difference between CT with and
      without PMA (DeltaCT) in liquid cultures treated with one of six anti
      tuberculosis drugs (isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin,
      moxifloxacin) and found significant DeltaCT only with isoniazid and ethambutol
      for pan-susceptible M. tuberculosis and only with ethambutol for extensively drug
      resistant M. tuberculosis. In the clinic we assessed DeltaCT in sputum samples
      collected from patients with pulmonary tuberculosis before and at regular
      intervals over 12 weeks after initiation of treatment. Before treatment start,
      estimated CT were 19.3 (95% CI: 17.1-21.4) and 19.8 (95% CI: 17.6-22.1) without
      and with PMA, respectively. Under treatment CT increased by 2.54 per ??day (95%
      CI: 1.38-3.69) without PMA and an additional 0.55 per ??day (95% CI: 0.37-0.74; p
      < 0.0001) with PMA. We conclude that PMA increases the specificity of Xpert for
      viable M. tuberculosis but the effect is small and dependent on the antibiotics
      used.

PMID- 27865404
TI  - Formulation studies of InhA inhibitors and combination therapy to improve
      efficacy against Mycobacterium tuberculosis.
AB  - Previously, structure-based drug design was used to develop substituted diphenyl
      ethers with potency against the Mycobacterium tuberculosis (Mtb) enoyl-ACP
      reductase (InhA), however, the highly lipophilic centroid compound, SB-PT004,
      lacked sufficient efficacy in the acute murine Mtb infection model. A next
      generation series of compounds were designed with improved specificity, potency
      against InhA, and reduced cytotoxicity in vitro, but these compounds also had
      limited solubility. Accordingly, solubility and pharmacokinetics studies were
      performed to develop formulations for this class and other experimental drug
      candidates with high logP values often encountered in drug discovery. Lead
      diphenyl ethers were formulated in co-solvent and Self-Dispersing Lipid
      Formulations (SDLFs) and evaluated in a rapid murine Mtb infection model that
      assesses dissemination to and bacterial burden in the spleen. In vitro synergy
      studies were performed with the lead diphenyl ether compounds, SB-PT070 and SB
      PT091, and rifampin (RIF), which demonstrated an additive effect, and that guided
      the in vivo studies. Combinatorial therapy in vivo studies with these compounds
      delivered in our Self-Micro Emulsifying Drug Delivery System (SMEDDS) resulted in
      an additional 1.4 log10 CFU reduction in the spleen of animals co-treated with SB
      PT091 and RIF and an additional 1.7 log10 reduction in the spleen with animals
      treated with both SB-PT070 and RIF.

PMID- 27865405
TI  - Identification of SP110 in horse (Equus caballus): Isolation of novel splice
      variants and evidence of activation effects on macrophages.
AB  - SP110 has previously shown to be a genetic determinant of host resistance to the
      intracellular pathogen infection in mouse and human. However, its relevant
      biological information in large non-primate animals still remains unknown. Here
      we report the novel discovery and characterization of three transcript variants
      of horse SP110. The transcript variant 1 (Tv1) of horse SP110 with the longest
      open reading frame has four domains (Sp100, SAND, PHD and Bromo domain). Tv2 and
      Tv3 share the same N-terminal sequence as Tv1, which contains Sp100 and SAND. We
      show that Tv2 is generated from alternative splicing and deletion of Exon17
      Exon18 segment, while Tv3 is generated by pre-mature transcriptional termination
      at Exon 16. Furthermore, we demonstrate that the heterologous expression of horse
      SP110 variants stimulate macrophages into an activation-like phenotype. The
      macrophages underwent a shift in enhancing the secretion of cytokines
      (interleukin-1 (IL-1) and TNF-alpha) and accelerating inducible nitric oxide
      synthase (iNOS) activity, and eventually went into apoptotic cell death.
      Intriguingly, horse SP110 Tv1 showed more capability to trigger the immune
      activities compared to Tv2 and Tv3. To our knowledge, the identification of SP110
      transcript variants from horse is the first report on biological function of
      SP110 in perissodactyla animals.

PMID- 27865406
TI  - An adverse immune-endocrine profile in patients with tuberculosis and type 2
      diabetes.
AB  - Diabetes is a risk factor for the development of pulmonary tuberculosis (TB) and
      both diseases present endocrine alterations likely to play a role in certain
      immuno-endocrine-metabolic associated disorders. Patients with TB, or with TB and
      type 2 diabetes (TB + T2DM) and healthy controls (HCo) were assessed for plasma
      levels of cortisol, dehydroepiandrosterone (DHEA), estradiol, testosterone,
      growth hormone (GH), prolactin, insulin-like growth factor-1 (IGF-1), cytokines
      (IL-6, IL-10, IFN-gamma) and the specific lymphoproliferative capacity of
      peripheral blood mononuclear cells. All patients had higher levels of cortisol
      with a reduction in DHEA, thus resulting in an increased cortisol/DHEA ratio
      (Cort/DHEA). Increased prolactin and particularly GH levels were found in both
      groups of TB patients. This was not paralleled by increased concentrations of
      IGF, which remained within the levels of HCo. Estradiol levels were significantly
      augmented in patients TB, and significantly more in TB + T2DM, whereas
      testosterone levels were decreased in both groups of patients. IFN- gamma and IL
      6 concentrations were significantly increased in all TB, even further in TB +
      T2DM; while IL-10 was equally increased in both groups of TB patients. The in
      vitro specific proliferative capacity was decreased in both groups of patients as
      compared to that of HCo. The adverse immune-endocrine profile of TB seems to be
      slightly more pronounced in patients who also have T2DM.

PMID- 27865407
TI  - Resveratrol prevents capacitation-like changes and improves in vitro fertilizing
      capability of buffalo frozen-thawed sperm.
AB  - The aim of this study was to evaluate the effect of resveratrol supplementation
      of semen extender on fertility parameters of frozen-thawed buffalo sperm. After
      the initial semen assessment, buffalo semen was cryopreserved in BioXcell
      containing 0 (control group), 0.5, 1, 10, and 50-MUM resveratrol. After thawing,
      viability, motility, and capacitation status (assessed by localization of
      phosphotyrosine-containing proteins) were evaluated. Based on the results of the
      dose-response trial, the concentration of 50 MUM was selected for further
      assessments, such as membrane integrity, total antioxidant capacity, reactive
      oxygen species, and lipid peroxidation (LPO) levels. Moreover, in vitro
      fertilizing ability by heterologous IVF and in vivo fertility were assessed. No
      differences among groups were recorded in sperm motility and viability (on
      average 52.3 +/- 2.1% and 76.6 +/- 1.3%, respectively). However, data showed a
      resveratrol dose-dependent effect on sperm capacitation status, with a
      significant reduction of the cryopreservation-induced capacitation with the
      higher concentrations tested. In particular, both 10- and 50-MUM resveratrol
      increased (P < 0.01) the percentage of sperm displaying pattern A (low
      capacitation level), but treatment with 50-MUM resveratrol also decreased (P <
      0.01) the proportion of sperm exhibiting pattern EA (high-capacitation level)
      compared with the control. Interestingly, supplementation of semen extender with
      resveratrol increased membrane integrity, indicated by the higher percentage of
      hypo-osmotic swelling positive sperm (55.6 +/- 0.6 vs. 48.4 +/- 0.7; P < 0.01),
      and total antioxidant capacity (1.36 +/- 0.01 vs. 1.32 +/- 0.02 mM/L; P < 0.05)
      compared with the control. Intracellular reactive oxygen species decreased in
      resveratrol-treated sperm compared with the control, as indicated by
      dihydroethidium values (0.17 +/- 0.01 and 0.22 +/- 0.01 MUM/MUL dihydroethidium,
      respectively; P < 0.01). Moreover, when IVF was carried out by using semen
      treated with 50 MUM resveratrol, the normal fertilization rate considerably
      improved (60.8%, P < 0.05) compared with the control (51.3%). However, no
      differences were recorded in pregnancy rates at 60 days post-AI with resveratrol
      treated semen (50 MUM) compared with the control (48.7 vs. 46.5%, respectively).
      In conclusion, the inclusion of 50-MUM resveratrol in the extender decreases
      capacitation-like changes and oxidative stress, improving membrane stability and
      in vitro fertilizing ability of buffalo semen.

PMID- 27865408
TI  - Progesterone and ultrasonographic changes during aglepristone or cloprosternol
      treatment in queens at 21 to 22 or 35 to 38 days of pregnancy.
AB  - Progesterone (P4) is a requirement for pregnancy development. Previous reports
      observed a maximal value of serum P4 concentration on 21 days after the first
      mating after which it slowly declines throughout the rest of pregnancy.
      Ultrasound examination should be performed to ensure that pregnancy interruption
      is complete. Limited information is available on the ultrasonic appearance of
      conceptuses during pregnancy termination in cats The objective was to study serum
      P4 concentration and ultrasonographic changes during aglepristone (ALI) or
      cloprostenol (CLO) treatment and to evaluate the fertility after treatment. Two
      experiments (EXP) were carried out to accomplish this aim. Sixty queens, 12- to
      36-month-old, were used. On Days 21 to 22 of pregnancy (EXP I) or 35 to 38 of
      pregnancy (EXP II), queens were divided into three groups (G). Queens in G1
      received ALI (10 mg/kg, sc; EXP I, n = 10; EXP II, n = 10) for 2 consecutive
      days. Queens in G2 received CLO (5 MUg/kg, sc; EXP I, n = 10; EXP II = 10) for 3
      consecutive days. Queens in G3 received 1 mL of saline solution (PLA, sc; EXP I,
      n = 10; EXP II = 10). Blood samples were taken before treatment (Day 0) and every
      day during 10 days after the treatment to measure serum P4 concentrations.
      Likewise, after treatment, queens were monitored daily by ultrasonography for 10
      days and weekly until the end of gestation to obtain gestational sacs
      measurements (GS), fetal measurements, and fetal biophysical profile. Data were
      analyzed by ANOVA. Serum P4 concentrations were significantly different on Day 6
      (EXP I) and on Day 1 (EXP II) in ALI and CLO groups compared with PLA group (P <
      0.05 and P < 0.01; respectively). The ultrasonographic monitoring during
      treatment allowed assessing changes in the GS and fetal measurements, embryo
      fetal viability, and risk of pregnancy loss. In conclusion, the results from this
      study reported changes in serum P4 concentration and in ultrasonography
      measurements during pregnancy interruption with ALI or CLO treatment. Also it was
      observed that ALI and CLO are safe drugs and can preserve posttreatment queen
      fertility. Therefore, the results obtained in our work will be applied in feline
      reproduction practice.

PMID- 27865409
TI  - High somatic cell counts and changes in milk fat and protein contents around
      insemination are negatively associated with conception in dairy cows.
AB  - The fertility of dairy cows has decreased dramatically worldwide over the last
      few decades, and several causes of this trend have been reported. Several studies
      have associated compromised udder health with deteriorating reproduction
      performance. Subclinical ketosis (SCK) has also been reported to be a risk factor
      for decreased conception. The objective of the present study was to describe how
      SCK might interact with the reported association between udder health and
      conception in dairy cows. Data from the French Milk Control Program and data on
      8,549,667 instances of artificial insemination (AI) and their corresponding
      preceding and subsequent test-days from 5,979,701 Holstein cows were examined
      over a 5-year period (2008-2012). The effect of udder health was evaluated
      through a low (L) or high (H) somatic cell count (SCC) before and after AI using
      a threshold of 200,000 cells/mL, and transformed into four groups (LL, LH, HL,
      and HH). Three proxies for defining SCK were proposed based on the milk fat and
      protein content (or their ratio) before AI. Statistical analysis first included a
      generalized additive model to help define the optimal threshold values. Next, a
      logistic regression with a Poisson correction was performed. On average, the risk
      of conception at first AI was reduced by 14% for LH or HH cows (relative risk
      [and 95% CI] = 0.86 [0.85-0.87]) when the SCC increased or remained high within
      40 days before and after AI, relative to LL group. The reduction of conception
      success associated with SCK (fat and protein contents changes) varied from 3% to
      17% depending on the used SCK proxy. Including the interaction term SCC*SCK
      clearly showed that the association of increased SCC around AI with conception
      success was modified by the presence of SCK. A cow that already has SCK and
      experiences an increase in SCC around or after AI exhibits up to 2 times further
      decrease in conception success compared with a cow with a high SCC and no SCK. In
      conclusion, this study reinforces the previously described association between
      intramammary inflammation around or after AI and a decreased rate of conception.
      These findings highlight how SCK interacts with the above-mentioned relationship
      by strengthening the negative association between mastitis and conception
      success. In addition, the present work supports the theory that local
      inflammation may affect the whole-body response and alter the functions of other
      organs, such as the reproductive tract.

PMID- 27865410
TI  - Comparative analysis of testis transcriptomes associated with male infertility in
      cattleyak.
AB  - Cattleyak exhibit equivalent adaptability to harsh environment as yak and much
      higher performances than yak. However, male infertility of cattleyak due to
      spermatogenic arrest greatly restricts their effective utilization in yak
      breeding. Although much work has been done to investigate the mechanisms of
      spermatogenic arrest, there is little information available in regard to the
      differences in transcriptomic profiling between cattleyak and yak testes. In this
      work, histologic observation indicated that spermatogonia were the main type of
      germ cells present in cattleyak testis, whereas all types of germ cells in
      differentiation were present in yak testis. Transcriptomic profiling identified
      2960 differentially expressed genes (DEGs) in which 679 were upregulated and 2281
      were downregulated in cattleyak. Significantly enriched gene ontology terms
      comprised a large number of DEGs associated with male infertility of cattleyak.
      The upregulation of STRA8 and NLRP14 may be associated with the accumulation of
      undifferentiated spermatogonial cells and serious cellular apoptosis in
      cattleyak. However, downregulated SPP1, SPIN2B, and PIWIL1 were associated with
      cell cycle progression and spermatogonial genome integrity, whereas CDKN2C,
      CYP26A1, OVOL1, GGN, MAK, INSL6, RNF212, TSSK1B, TSSK2, and TSSK6 were involved
      in meiosis. Furthermore, scores of genes associated with sperm components were
      also downregulated in cattleyak. Wnt/beta-catenin signaling pathway was involved
      in the top-listed three significantly enriched pathways, and the downregulation
      of Wnt3a, PP2A, and TCF/LEF-1 may have contributed to the arrest of
      spermatogonial differentiation in cattleyak. The data suggest that spermatogenic
      arrest of cattleyak might occur at the stage of spermatogonial differentiation
      and get aggravated during meiosis, which results in minimal number of sperms with
      morphologic abnormalities and structural deficiency lacking fertilization
      ability.

PMID- 27865411
TI  - Low levels of apoptotic-like changes in fresh and cryopreserved feline
      spermatozoa collected from the urethra and epididymis.
AB  - The aim of this study was to examine apoptotic markers in fresh and frozen-thawed
      feline spermatozoa collected via urethral catheterization and epididymal slicing.
      Caspase activation, DNA fragmentation, and phosphatidylserine externalization
      were evaluated using flow cytometry in sperm cells from both sources before and
      after cryopreservation. The study revealed no differences between urethral and
      epididymal spermatozoa, both in fresh and frozen-thawed samples. The level of
      apoptotic changes in sperm cells in fresh feline semen was low: 0.8 +/- 0.8% of
      live urethral and 0.4 +/- 0.4% of live epididymal spermatozoa showed active
      caspases; 1.6 +/- 0.9% and 2.1 +/- 1.9%, respectively, showed DNA fragmentation;
      and 0.3 +/- 0.2% and 1.0 +/- 1.3%, respectively, showed phosphatidylserine
      externalization. In both types of sperm cells, cryopreservation did not induce a
      significant increase in caspase activation (urethral: from 3.9 +/- 3.2% to 7.5 +/
      5.0%; epididymal: from 4.7 +/- 2.9% to 11.7 +/- 8.5%). In urethral spermatozoa,
      phosphatidylserine externalization in live cells was significantly (P < 0.05)
      increased after thawing (from 0.3 +/- 0.2% to 2.7 +/- 2.5%). This increase was
      not noted for epididymal spermatozoa (from 1.0 +/- 1.3% to 1.7 +/- 1.3%). No
      significant changes in DNA fragmentation were observed (2.1 +/- 0.8% and 1.7 +/-
      1.0%). In conclusion, both urethral and epididymal feline spermatozoa showed
      equally low levels of apoptotic-like changes. Hence, apoptotic alterations seem
      to play only a minor role, if any, in urethral and epididymal feline spermatozoa.
      The deterioration of sperm quality after freezing and thawing is more likely
      connected with direct damage to the cells than to activation of apoptotic
      processes.

PMID- 27865412
TI  - Expression and localization of matrix metalloproteinases (MMP-2, -7, -9) and
      their tissue inhibitors (TIMP-2, -3) in the chicken oviduct during pause in
      laying induced by tamoxifen.
AB  - Induced pause in egg laying simulates natural molting events in which the hen's
      reproductive organs regress and rejuvenate. Such processes require extracellular
      matrix remodeling that is maintained, at least in part, by the action of
      proteolytic enzymes known as matrix metalloproteinases (MMPs). Nevertheless,
      information concerning the expression and hormonal regulation of MMP system
      members in chickens is scarce. Therefore, MMP-2, -7, and -9 and their tissue
      inhibitors (TIMP-2, -3) expression and localization were investigated in all
      segments of the domestic hen oviduct (infundibulum, magnum, isthmus, shell gland,
      vagina) during a pause in egg laying induced by tamoxifen (TMX)-an estrogen
      receptor modulator. Hy-Line Brown hens were treated daily with TMX (n = 6) at a
      dose of 6 mg/kg of body weight or a vehicle (n = 6) until complete cessation of
      egg laying (for 7 days). Chickens were decapitated on Day 7 of the experiment.
      Real-time polymerase chain reaction and Western blotting revealed section
      dependent expression of MMP-2, -7, -9 and TIMP-2 and -3. Immunohistochemistry
      found tissue and cell-dependent localization of examined proteins in the wall of
      the oviduct. The MMP-2, TIMP-2, and TIMP-3 were localized mainly in the luminal
      epithelium, MMP-7 in the luminal and glandular epithelium, whereas MMP-9 was
      detected only in the connective tissue. Treatment of chickens with TMX markedly
      elevated the relative expression of MMP-7 and MMP-9 mRNA in the oviduct, but did
      not affect MMP-2, TIMP-2, and TIMP-3 mRNA levels. However, TMX increased the MMP
      2 protein level in the infundibulum, shell gland, and vagina as well as activity
      of MMP-2 evaluated by gelatin zymography. The results obtained indicate that MMP
      2, MMP-7, and MMP-9 are involved in chicken oviduct regression. Moreover, changes
      in the expression and activity of chosen MMPs after TMX treatment may indicate a
      contribution of estrogen in the regulation of transcription, translation, and/or
      the activity of selected elements of the MMP system.

PMID- 27865413
TI  - Evaluation of chlorhexidine hydrochloride treatment on endometrial health of
      normal mares.
AB  - Chlorhexidine gluconate solution is a potent antimicrobial and therefore could be
      used effectively for treatment of endometritis, but historically this substance
      has been implicated as irritating to mucous membranes, including the endometrium
      of the mare. The use of chlorhexidine hydrochloride suspension (Nolvasan
      Suspension, Zoetis, Florham Park, NJ, USA) was evaluated in the uterus of normal
      mares to determine if adverse effects on endometrial health were noted. Twelve
      healthy, adult light breed mares were included in this study. Procedures were
      approved by the Auburn University Institutional Animal Care and Use Committee.
      All mares were determined to be reproductively normal by evaluation of
      endometrial histopathology, cytology, and bacterial culture. Mares were randomly
      assigned to treatment or control groups (n = 6 per group). Each mare was treated
      during estrus with an intrauterine infusion of 1 g (28 mLs per tube; 35.7 mg/mL)
      of chlorhexidine hydrochloride suspension (treatment group) or an equal volume of
      lactated ringer's solution (control group) once daily for 3 consecutive days.
      Biopsy and cytology samples were taken 3, 7, and 14 days after completion of
      treatment. Cytology and biopsy samples were read by a board-certified pathologist
      (L.N.) blinded to treatments, and biopsy samples were graded using a standardized
      Kenney-Doig score. There was no difference with respect to biopsy grade, degree
      of endometrial fibrosis, or presence of cytologic inflammation comparing control
      and treatment groups (P = 0.55, 0.7, and 0.06, respectively), neither when
      accounting for sampling day. The suspension was visible within the uterine lumen
      when mares were examined with transrectal ultrasonography for up to 4 days after
      treatment. Treatment with chlorhexidine hydrochloride in this formulation and at
      this concentration does not appear to have a deleterious effect on short term
      endometrial health in mares.

PMID- 27865414
TI  - Association between polymorphisms in somatotropic axis genes and fertility of
      Holstein dairy cows.
AB  - The aim of this study was to determine the effect of growth hormone receptor
      (GHR) AluI, insulin-like growth factor type 1 (IGF-I) SnaBI, and signal
      transducer and activator 5A (STAT5A) BstEII polymorphisms in the reproductive
      performance of Holstein dairy cows and the frequency of this genotypes in cows
      managed in different systems. This work studied 381 and 506 Holstein cows from
      semiextensive and intensive systems, respectively. The frequency of genotypes
      GHRAluI (+/-), IGF-ISnaBI (-/-) and (+/-), and STAT5ABstEII (-/-) was higher in
      animals from semiextensive system, whereas the frequency of the genotypes GHRAluI
      (+/+) and IGF-ISnaBI (+/+) was higher in animals from intensive system (P <
      0.05). In the intensive system, cows from the STAT5ABstEII (-/-) genotype had a
      longer calving-first heat interval (P = 0.03). In conclusion, there was no
      association between the genotypes of GHRAluI and IGF-ISnaBI and fertility of
      Holstein cows raised in semiextensive or intensive regimes, although the genotype
      frequencies of the evaluated polymorphisms were different between the studied
      systems. The STAT5ABstEII polymorphism was associated with calving-first heat
      interval in Holstein cows raised in the intensive system, indicating that this
      gene could be a molecular marker for genetic selection to improve reproductive
      performance.

PMID- 27865415
TI  - Biosterilant effects of Bacillus thuringiensis kurstaki HD-73 extract on male
      Wistar albino rats.
AB  - Chemosterilants have long been used in sterilization programs for managing pet,
      stray, and wild animals but adverse effects such as trauma, incomplete responses
      to treatment, and complete abolition of gonadal sources of testosterone often
      occurs. This study describes the biosterilant effects of administering three
      doses of Bacillus thuringiensis kurstaki HD-73 (Bt 5, 50, and 250 mg/kg; 20
      rats/dose) extract in adult male Wistar albino rats on testicular parameters,
      function, histology, and a number of biochemical markers of overall health, free
      radical production, and cell proliferation. Intratesticular administration of Bt
      extract to rats induces testicular oxidative stress and damages and consequently,
      perturb spermatogenesis, degeneration of testis, reduction in testes size, and
      depletion of testosterone and antioxidant enzyme concentrations in a dose
      dependent manner because of free radical-mediated lipid peroxidation. No
      morbidity or mortality adverse effects were observed in both the saline control
      and Bt extract-treated rats. Significant variation was noted in clinical
      manifestations, weight and volume of testes, and hormonal and biochemical
      profiles between Bt doses in comparison with the saline control.
      Aspermia/azoospermia (100%) resulted in Bt-treated rats without any adverse
      effects. Histopathological analysis showed degeneration, necrosis, vacuolation,
      fewer germ cells, formation of multinucleated giant cells, and a lack of
      elongated spermatids in atrophic seminiferous tubules in Bt extract-treated
      groups in the presence of low concentrations of testosterone, antioxidant
      enzymes, and suppression of germ cell proliferation. Dose-dependent effects were
      evident in most parameters that were measured. The vast array of tests that were
      undertaken also provides some important indicators of the physiological effects
      associated with the treatments that were applied. Intratesticular injection of Bt
      extract impairs spermatogenesis and induces permanent sterility in rats.

PMID- 27865416
TI  - Embryo yield in dairy cattle after superovulation with Folltropin or Pluset.
AB  - Two commercial FSH products were compared in a retrospective study on 3990
      commercial superovulations and embryo recoveries in dairy heifers and cows. In
      addition, the 56-day nonreturn rate of 19,400 embryos produced with these two
      preparations was analyzed. Embryo collections were performed during a 16-year
      period from donors of Holstein and Ayrshire breeds. Folltropin (Vetoquinol S.A.,
      Lure cedex, France) group (Group F) consisted of 2592 superovulations, of which
      80% were performed on heifers and 20% on cows, and Pluset (Laboratorios Calier,
      S.A., Barcelona, Spain) group (Group P) of 1398 treatments, of which 66% and 34%
      were on heifers and cows, respectively. Total number of recovered structures,
      number of transferable embryos, and the proportion of unfertilized ova (UFO) and
      degenerated embryos were analyzed. Distribution of embryos into quality grades (1
      3) and developmental stages (4-9) according to the IETS classification guidelines
      and means for each collection were evaluated. The proportion of low-responders
      having fewer than five corpora lutea and yielding fewer than five embryos or ova
      was investigated for each treatment. Group P yielded 1.1 recovered structures
      more than Group F (P < 0.001). Consequently, however, the number of transferable
      embryos did not differ among the groups, being 7.0 and 7.1 in Groups F and P,
      respectively. Instead, there was an increase in the number of UFO from 2.0 in
      Group F to 3.0 in Group P (P < 0.001). The quality of embryos and the
      developmental stages were similar between the groups and there was no difference
      in the proportion of low-responding donors in Group F and Group P. Also, there
      was no difference in the nonreturn rate after transfer of embryos originating
      from donors superovulated with Folltropin or Pluset. It was concluded that equal
      numbers of transferable embryos and pregnancies can be achieved with Folltropin
      and Pluset.

PMID- 27865417
TI  - Knock-down of apoptosis inducing factor gene protects endoplasmic reticulum
      stress-mediated goat granulosa cell apoptosis.
AB  - The apoptosis of granulosa cells is the main cause of follicular atresia, and
      endoplasmic reticulum (ER) stress is involved in the apoptosis of granulosa
      cells. Apoptosis inducing factor (AIF) mediates caspase-independent apoptosis and
      causes chromatin condensation and DNA fragmentation, but its role in ER stress
      mediated granulosa cell apoptosis during goat follicular atresia remains largely
      unknown. The aim of this study was to investigate the function of AIF in the
      apoptosis of goat granulosa cells mediated by ER stress. The results of
      immunohistochemical and Western blot analyses demonstrated that AIF was mainly
      located in granulosa cells, and the expression of AIF significantly increased
      during follicular atresia. Then, AIF-short hairpin RNA recombinant lentiviral
      vectors were constructed successfully and transfected into human telomerase
      reverse transcriptase-goat granulosa cells (hTERT-GGCs). Real-time quantitative
      polymerase chain reaction and Western blot analysis confirmed that AIF was
      effectively knocked down in hTERT-GGCs. Flow cytometry results showed that the
      knockdown of AIF in hTERT-GGCs reduced apoptosis due to serum starvation or
      thapsigargin (Tg) treatment. In addition, AIF depletion changed the expression of
      related molecular marker molecules of ER stress under Tg treatment. In
      conclusion, AIF may serve as a key factor during follicular atresia, and AIF
      depletion protects ER stress-mediated goat granulosa cell apoptosis.

PMID- 27865418
TI  - Characterizing emergence and divergence in the first follicular wave in a
      tropically adapted Bos taurus breed.
AB  - Tropically adapted Bos taurus breeds are descended from the cattle which were
      brought from the Iberian Peninsula to Latin America by the colonizers and which
      adapted over time to local conditions. These breeds have become a genetic
      treasure that must be preserved. The objective of this study was to characterize
      ovarian follicular emergence and divergence in tropically adapted B. taurus cows
      and heifers. Cyclic heifers (n = 11) and nonlactating, multiparous cows (n = 11)
      were examined at 8-hour intervals using ultrasonography starting on the day
      following the final application of PGF2alpha, which was used to synchronize the
      estrous cycle, and ending 5 days after ovulation. Blood samples were collected
      immediately following the ultrasonographic examinations in order to evaluate FSH
      and estradiol-17beta (E2) concentrations. The interval between ovulation and
      follicular wave emergence (11.6 +/- 3.3 hours vs. 20.3 +/- 2.5 hours, P < 0.05)
      and ovulation and follicular wave divergence (52.4 +/- 5.2 hours vs. 71.8 +/- 4.1
      hours, P < 0.05) was shorter in the cows than in the heifers, respectively.
      Plasma FSH concentrations increased (P < 0.05) and serum E2 concentrations
      decreased earlier in cows than in heifers before ovulation. Following follicular
      wave emergence, no difference in follicular development was found between the
      cows and the heifers. Consequently, following follicular wave emergence, the data
      from both the cows and the heifers were combined and categorized by dominant
      follicle (DF) and second largest follicle (SF). The DF and SF were identified at
      the same time (P > 0.05). The mean number of small (<=4 mm, 7.2 +/- 5.1) and
      medium (4 to <= 8 mm, 6.8 +/- 3.5) follicles was greater than that of large
      follicles (>=8 mm, 0.6 +/- 0.5) from ovulation until 5 days after ovulation. The
      DF diameter (8.1 +/- 1 mm) did not differ (P = 0.09) from SF diameter (7.6 +/-
      0.9 mm) at the time of follicular divergence (around 45 hours after follicular
      emergence). The DF and SF growth rates were similar (P > 0.05) until follicular
      divergence, at which point the SF growth rate decreased, whereas the DF growth
      rate remained constant. Serum E2 concentrations did not change (P > 0.05) during
      the divergence period, whereas FSH concentrations decreased between 48 and 32
      hours before follicular wave divergence. In conclusion, cows and heifers differed
      only in the interval from ovulation to follicular wave emergence and divergence,
      which was confirmed by the different patterns of FSH and E2 concentrations.

PMID- 27865420
TI  - Towards value-based universal Lynch syndrome identification in endometrial cancer
      patients.

PMID- 27865419
TI  - GPR39 is region-specifically expressed in mouse oviduct correlating with the Zn2+
      distribution.
AB  - G-protein-coupled receptor 39 (GPR39) plays a role in cellular and physiological
      processes, including insulin secretion, cell death inhibition, wound healing, and
      obesity. Increasing evidence suggests that GPR39 is potently stimulated by zinc
      ions (Zn2+) and is therefore considered a putative Zn2+ receptor. Given the
      importance of Zn2+ in the reproductive system, we proposed that GPR39 might have
      a functional role in the reproductive system. However, the localization of GPR39
      in the reproductive system remains unknown. Here, we used mice expressing a Gpr39
      promoter-driven LacZ reporter system to detect Gpr39 expression in the
      reproductive system at different phases of the estrous cycle and found an
      interesting region-specific distribution of Gpr39 in the mouse oviduct
      epithelium, with strong expression at the ampulla and weak expression at the
      isthmus, which was consistent with the results using reverse transcription
      polymerase chain reaction and immunofluorescence. Moreover, using ZnSeAMG
      staining, we found that Zn2+, the putative ligand of GPR39, also found a
      distribution similar to GPR39 expression, suggesting that their potential
      interaction mediates fertilization and embryo transportation.

PMID- 27865422
TI  - We've come a long way: Let the work begin.

PMID- 27865423
TI  - Embryonal Rhabdomyosarcoma of the Oesophagus in a Young Dog.
AB  - A 15-month-old great Dane dog, showing clinical signs related to hypertrophic
      osteopathy, was diagnosed radiographically with a mass in the region of the
      thoracic oesophagus. Exploratory thoracotomy revealed an extensive, highly
      vascularized and locally invasive oesophageal mass and the presence of nodules in
      adjacent lung lobes. The dog was humanely destroyed intra-operatively.
      Histological examination revealed that the mass was an embryonal
      rhabdomyosarcoma. This is the first report of rhabdomyosarcoma of the oesophagus
      of a dog. Rhabdomyosarcoma should be considered a differential diagnosis when a
      mass adjacent to the oesophagus is diagnosed.

PMID- 27865424
TI  - Surface-bound microgels - From physicochemical properties to biomedical
      applications.
AB  - Microgels offer robust and facile approaches for surface modification, as well as
      opportunities to introduce biological functionality by loading such structures
      with bioactive agents, e.g., in the context of drug delivery, functional
      biomaterials, and biosensors. As such, they provide a versatile approach for the
      design of surfaces with pre-determined characteristics compared to more elaborate
      bottom-up approaches, such as layer-by-layer deposition and surface-initiated
      polymerization. In the present overview, properties of surface-bound microgels
      are discussed, ranging from physical adsorption and covalent grafting in dilute
      systems, to directed self-assembly, multilayer structures, and composites, as
      well as loading an release of drugs and other cargo molecules into/from such
      systems, and biomedical applications of these.

PMID- 27865421
TI  - Cannabidiol (CBD) induces functional Tregs in response to low-level T cell
      activation.
AB  - Many effects of the non-psychoactive cannabinoid, cannabidiol (CBD), have been
      described in immune responses induced by strong immunological stimuli. It has
      also been shown that CBD enhances IL-2 production in response to low-level T cell
      stimulation. Since IL-2, in combination with TGF-beta1, are critical for Treg
      induction, we hypothesized that CBD would induce CD4+CD25+FOXP3+ Tregs in
      response to low-level stimulation. Low-level T cell stimulation conditions were
      established based on minimal CD25 expression in CD4+ cells using suboptimal
      PMA/Io (4nM/0.05MUM, S/o), ultrasuboptimal PMA/Io (1nM/0.0125MUM, Us/o) or
      soluble anti-CD3/28 (400-800ng each, s3/28). CBD increased CD25+FOXP3+ cells from
      CD4+, CD4+CD25+, and CD4+CD25- T cells, as well as in CD4+ T cells derived from
      FOXP3-GFP mice. Most importantly, the Us/o+CBD-induced CD4+CD25+ Tregs robustly
      suppressed responder T cell proliferation, demonstrating that the mechanism by
      which CBD is immunosuppressive under low-level T cell stimulation involves
      induction of functional Tregs.

PMID- 27865425
TI  - Zika virus infection during the Olympic Games in Rio: A fear or an actual risk?
AB  - The recent outbreak of Zika virus infection in Brazil has aroused considerable
      media interest due to its association with neurological malformations in children
      born from mothers infected by the virus and to its association with Guillain
      Barre syndrome in adults. This relationship has led to the World Health
      Organisation declaring the current epidemic as a "Public Health Emergency of
      International Concern". Controversy also emerged on the advisability of delaying
      or changing the location of the Olympic and Paralympic Games, which were held in
      August at various locations in Brazil. In this article, we review the available
      evidence on the risk of Zika and dengue virus infection in individuals who travel
      to endemic countries, especially for multitudinous events.

PMID- 27865426
TI  - Surgical treatment of acute diverticulitis. A retrospective multicentre study.
AB  - INTRODUCTION: To analyze short and medium-term results of different surgical
      techniques in the treatment of complicated acute diverticulitis (CAD). METHODS:
      Multicentre retrospective study including patients operated on as surgical
      emergency or deferred-urgency with the diagnosis of CAD. RESULTS: A series of 385
      patients: 218 men and 167 women, mean age 64.4+/-15.6 years, operated on in 10
      hospitals were included. The median (25th-75th percentile) time from symptoms to
      surgery was 48 (24-72) h, being peritonitis the main surgical indication in a 66%
      of cases. Surgical approach was usually open (95.1%), and the commonest findings,
      a purulent peritonitis (34.8%) or pericolonic abscess (28.6%). Hartmann procedure
      (HP) was the most used technique in 278 (72.2%) patients, followed by resection
      and primary anastomosis (RPA) in 69 (17.9%). The overall postoperative morbidity
      and mortality was 53.2% and 13% respectively. Age, immunosupression, presence of
      general risk factors and faecal peritonitis were associated with increased
      mortality. Laparoscopic peritoneal lavage (LPL) was associated with an increased
      reoperation rate frequently involving a stoma, and anastomotic leaks presented in
      13.7 patients after RPA, without differences in morbimortality when compared with
      HP. Median postoperative length of stay was 12 days, and was correlated with age,
      surgical risk, ASA score, hospital and postoperative complications. CONCLUSIONS:
      Surgery for CAD has important morbidity and mortality and is frequently
      associated with an end-stoma. Moreover LPL presented high reoperation rates. It
      seems better to resect and anastomose in most cases, even with an associated
      protective stoma.

PMID- 27865427
TI  - De Garengeot's hernia: Incarcerated femoral hernia containing the vermiform
      appendix. Report of two cases and literature review.

PMID- 27865428
TI  - Reply to: "Unique effect for fructose on lipoprotein risk factors for
      cardiovascular disease in children is not demonstrated".

PMID- 27865429
TI  - Maternal Education Is Associated with Disparities in Breastfeeding at Time of
      Discharge but Not at Initiation of Enteral Feeding in the Neonatal Intensive Care
      Unit.
AB  - OBJECTIVE: To investigate the relationship between maternal education and
      breastfeeding in very preterm infants admitted to neonatal intensive care units.
      STUDY DESIGN: This prospective, population-based cohort study analyzed the data
      of all very preterm infants admitted to neonatal care during 1 year in 3 regions
      in Italy (Lazio, Emilia-Romagna, and Marche). The use of mothers' own milk was
      recorded at initial enteral feedings and at hospital discharge. We used
      multilevel logistic analysis to model the association between maternal education
      and breastfeeding outcomes, adjusting for maternal age and country of birth.
      Region was included as random effect. RESULTS: There were 1047 very preterm
      infants who received enteral feeding, and 975 were discharged alive. At
      discharge, the use of mother's own milk, exclusively or not, and feeding directly
      at the breast were significantly more likely for mothers with an upper secondary
      education or higher. We found no relationship between maternal education and type
      of milk at initial enteral feedings. However, the exclusive early use of the
      mother's own milk at initial feedings was related significantly with receiving
      any maternal milk and feeding directly at the breast at discharge from hospital,
      and the association with feeding at the breast was stronger for the least
      educated mothers. CONCLUSION: In this population-based cohort of very preterm
      infants, we found a significant and positive association between maternal
      education and the likelihood of receiving their mother's own milk at the time of
      discharge. In light of the proven benefits of maternal milk, strategies to
      support breastfeeding should be targeted to mothers with less education.

PMID- 27865430
TI  - Apnea in the Otherwise Healthy, Term Newborn: National Prevalence and Utilization
      during the Birth Hospitalization.
AB  - OBJECTIVES: To describe the prevalence of apnea in otherwise healthy term
      newborns, identify attributable length of stay (LOS) and healthcare utilization
      (cost) of apnea, and measure hospital variation in attributable LOS and cost of
      apnea in this population. STUDY DESIGN: We conducted a secondary analysis of a
      national administrative dataset, the 2012 Kids' Inpatient Database, which
      included 3.4 million newborn discharges in the US. The birth hospitalizations of
      approximately 2.6 million otherwise healthy, full-term newborns were included for
      analysis. Attributable LOS and cost of apnea were calculated using multivariate
      analyses. RESULTS: Apnea was diagnosed in 1 in 1000 healthy full-term newborns.
      Multivariate analyses showed that newborns with apnea had 0.6 days longer LOS (P
      < .001) and $483 greater costs (P < .001) compared with healthy term newborns,
      per birth hospitalization. Newborns diagnosed with apnea plus hypoxia and/or
      bradycardia had 1.4 days longer LOS (P < .001) and $653 greater costs (P < .001).
      The attributable LOS and cost attributable to apnea varied between individual
      hospitals and differed by hospital region. CONCLUSIONS: Apnea is associated with
      higher LOS and cost in the newborn hospitalization, with variation in hospital
      practice. This suggests the need for better comprehension of the underlying
      physiology and standardization of practice in its management in the term newborn.

PMID- 27865431
TI  - Regression-based statistical mediation and moderation analysis in clinical
      research: Observations, recommendations, and implementation.
AB  - There have been numerous treatments in the clinical research literature about
      various design, analysis, and interpretation considerations when testing
      hypotheses about mechanisms and contingencies of effects, popularly known as
      mediation and moderation analysis. In this paper we address the practice of
      mediation and moderation analysis using linear regression in the pages of
      Behaviour Research and Therapy and offer some observations and recommendations,
      debunk some popular myths, describe some new advances, and provide an example of
      mediation, moderation, and their integration as conditional process analysis
      using the PROCESS macro for SPSS and SAS. Our goal is to nudge clinical
      researchers away from historically significant but increasingly old school
      approaches toward modifications, revisions, and extensions that characterize more
      modern thinking about the analysis of the mechanisms and contingencies of
      effects.

PMID- 27865432
TI  - A hybrid fault diagnosis approach based on mixed-domain state features for
      rotating machinery.
AB  - To make further improvement in the diagnosis accuracy and efficiency, a mixed
      domain state features data based hybrid fault diagnosis approach, which
      systematically blends both the statistical analysis approach and the artificial
      intelligence technology, is proposed in this work for rolling element bearings.
      For simplifying the fault diagnosis problems, the execution of the proposed
      method is divided into three steps, i.e., fault preliminary detection, fault type
      recognition and fault degree identification. In the first step, a preliminary
      judgment about the health status of the equipment can be evaluated by the
      statistical analysis method based on the permutation entropy theory. If fault
      exists, the following two processes based on the artificial intelligence approach
      are performed to further recognize the fault type and then identify the fault
      degree. For the two subsequent steps, mixed-domain state features containing time
      domain, frequency-domain and multi-scale features are extracted to represent the
      fault peculiarity under different working conditions. As a powerful time
      frequency analysis method, the fast EEMD method was employed to obtain multi
      scale features. Furthermore, due to the information redundancy and the
      submergence of original feature space, a novel manifold learning method (modified
      LGPCA) is introduced to realize the low-dimensional representations for high
      dimensional feature space. Finally, two cases with 12 working conditions
      respectively have been employed to evaluate the performance of the proposed
      method, where vibration signals were measured from an experimental bench of
      rolling element bearing. The analysis results showed the effectiveness and the
      superiority of the proposed method of which the diagnosis thought is more
      suitable for practical application.

PMID- 27865433
TI  - Influences of size-fractionated humic acids on arsenite and arsenate complexation
      and toxicity to Daphnia magna.
AB  - The intrinsic physicochemical properties of dissolved organic matter (DOM) may
      affect the mobility and toxicity of arsenic in aquatic environments. In the
      present study, the humic acid (HA) was ultra-filtered into five fractions
      according to molecular weight, and their physicochemical properties were
      characterized. Complexation of HA fractions with arsenite and arsenate was first
      determined by differential pulse polarography (DPP). The influences of HA
      fractions on arsenic toxicity were then examined using Daphnia magna as a model
      organism. As(V) had a higher affinity with HA than As(III), and their
      complexation was dependent on the total acidity and fluorescence characteristics
      of DOM. We demonstrated that the acidity and fluorescence also better explained
      the As toxicity to daphnids than UV absorbance and hydraulic diameter. Arsenic
      speciation determined by DPP significantly affected the toxicity of arsenite and
      arsenate. The results extended the free-ion activity model application to the
      case of arsenic. The present study clearly indicated that DOM with different
      molecular weights has distinct physicochemical properties, and could influence
      the speciation and toxicity of As to different extent.

PMID- 27865434
TI  - Potential water resource impacts of hydraulic fracturing from unconventional oil
      production in the Bakken shale.
AB  - Modern drilling techniques, notably horizontal drilling and hydraulic fracturing,
      have enabled unconventional oil production (UOP) from the previously inaccessible
      Bakken Shale Formation located throughout Montana, North Dakota (ND) and the
      Canadian province of Saskatchewan. The majority of UOP from the Bakken shale
      occurs in ND, strengthening its oil industry and businesses, job market, and its
      gross domestic product. However, similar to UOP from other low-permeability
      shales, UOP from the Bakken shale can result in environmental and human health
      effects. For example, UOP from the ND Bakken shale generates a voluminous amount
      of saline wastewater including produced and flowback water that are characterized
      by unusual levels of total dissolved solids (350 g/L) and elevated levels of
      toxic and radioactive substances. Currently, 95% of the saline wastewater is
      piped or trucked onsite prior to disposal into Class II injection wells. Oil and
      gas wastewater (OGW) spills that occur during transport to injection sites can
      potentially result in drinking water resource contamination. This study presents
      a critical review of potential water resource impacts due to deterministic
      (freshwater withdrawals and produced water management) and probabilistic events
      (spills due to leaking pipelines and truck accidents) related to UOP from the
      Bakken shale in ND.

PMID- 27865435
TI  - The pulse-mass index as a predictor of cardiovascular events in women with
      systemic lupus erythematosus.
AB  - BACKGROUND: Patients with systemic lupus erythematosus (SLE) have 3times the risk
      of death compared to the rest of the population, with cardiovascular events (CVD)
      being one of the main causes. Indices such as waist-height (W-Ht I), waist-hip (W
      Hp I) and pulse-mass (PMI) predict CVD, though the behaviour is unknown in
      patients with SLE. The aim of this study was to determine the prognostic value of
      PMI in the development of CVD in premenopausal women with SLE. METHODOLOGY:
      Cohort study. Included were premenopausal women with SLE without prior CVD;
      excluded were those patients with antiphospholipid syndrome (APS), pregnancy,
      thyroid disease, recent liposuction, and chronic kidney disease. Exposure
      variables were: PMI, W-Ht I, W-Hp I and metabolic syndrome at onset of the
      cohort. Considered confounding variables were time of evolution, disease
      activity, cumulative damage and treatment. Through semi-annual appointments,
      accident and emergency admittance and hospitalisation records the CVD were
      screened. Analysis was performed with Cox for proportional hazards and survival
      with Kaplan Meier. RESULTS: We included 238 women with a median age of 31 (18-52)
      years, with a follow-up of 8years. We identified 22 (9.6%) cases of CVD. In the
      Cox proportional hazards analysis, the prognostic variables were: PMI with HR=8.1
      (95% CI: 1.1-65), metabolic syndrome with 2.4 (95% CI: 1-5.8), cumulative damage
      with HR=1.5 (95% CI: 1.1-2.2) and body fat percentage HR=2.8 (95% CI: 1.1-6.9)
      CONCLUSIONS: The PMI is a better predictor factor of CVD in women with SLE.

PMID- 27865436
TI  - [Improving adverse drug reaction reporting by general practitioners through
      clinical research assistants visits].
AB  - The main limitation of adverse drug reactions (ADRs) reporting, particularly by
      general practitioners (GP), to the regional pharmacovigilance centers is under
      reporting. The Midi-Pyrenees Regional Pharmacovigilance Center (South western,
      France) sets up regular visits by a clinical research assistant (CRA) to GP in
      order to increase the number of ADR reports. The aim of this pilot study was to
      assess the effect of regular visits of a CRA in GPs offices on the rate of ADR
      reporting. After one year, CRA visits permit a two-fold increase in ADR
      reporting.

PMID- 27865437
TI  - Early neurodevelopmental outcomes of extremely preterm infants.
AB  - Infants born at extreme preterm gestation are at risk for both death and
      disability. Although rates of survival have improved for this population, and
      some evidence suggests a trend toward decreased neuromotor impairment over the
      past decades, a significant improvement in overall early neurodevelopmental
      outcome has not yet been realized. This review will examine the rates and types
      of neurodevelopmental impairment seen after extremely preterm birth, including
      neurosensory, motor, cognitive, and behavioral outcomes. We focus on early
      outcomes in the first 18-36 months of life, as the majority of large neonatal
      studies examining neurodevelopmental outcomes stop at this age. However, this
      early age is clearly just a first glimpse into lifetime outcomes; the
      neurodevelopmental effects of extreme prematurity may last through school age,
      adolescence, and beyond. Importantly, prematurity appears to be an independent
      risk factor for adverse development, but this population demonstrates
      considerable variability in the types and severity of impairments. Understanding
      both the nature and prevalence of neurodevelopmental impairment among extremely
      preterm infants is important because it can lead to targeted interventions that
      in turn may lead to improved outcomes.

PMID- 27865438
TI  - Evaluation of bone marrow derived mesenchymal stem cells for full-thickness wound
      healing in comparison to tissue engineered chitosan scaffold in rabbit.
AB  - BACKGROUND: Chronic wounds present a major challenge in modern medicine. Even
      under optimal conditions, the healing process may lead to scarring and fibrosis.
      The ability of mesenchymal stem cells (MSCs) to differentiate into other cell
      types makes these cells an attractive therapeutic tool for cell transplantation.
      Both tissue-engineered construct and MSC therapy are among the current wound
      healing procedures and potential care. Chitosan has been widely applied in tissue
      engineering because of its biocompatibility and biodegradability. AIM: The aim of
      the current work was to compare the efficiency of MSCs and chitosan dressing,
      alone or in combination treatment on wound healing. METHODS: This study was
      conducted on 15 rabbits, which were randomly divided in 3 groups based on the
      type of treatment with MSCs, chitosan dressing and combination of both. A full
      thickness skin defect was excised from the right and left side of the back of
      each animals. Defects on right sides were filled with treatments and left side
      defects were left as control. Evaluation of the therapeutic effectiveness was
      performed through a variety of clinical and microscopical evaluations and
      measurements of the process of wound healing on days 7, 14, 21, and 28.
      Histological evaluation of wound healing was classified by different scoring
      systems. RESULTS: The data indicated that wounds treated with bone marrow derived
      MSC had enhanced cellularity and better epidermal regeneration. During the early
      stages of wound healing, the closure rate of bone marrow derived MSC-treated
      wounds were significantly higher than other treatments (P<0.05). Although the
      MSCs in the wound edges enhance the healing of the full-thickness wound, the
      healing process of chitosan treatment was slower than the control group.
      CONCLUSION: This study revealed advanced granulation tissue formation and
      epithelialization in wounds treated with MSCs, and may suggests this treatment as
      an effective applicant in wound healing process. Chitosan scaffold dressings,
      whether alone or in combination with MSCs, have worsened the wound healing as
      compared to the control group.

PMID- 27865439
TI  - A scratch by any other name: A comment on Lucas et al.'s reply to "Scratching the
      surface: A critique of Lucas et al. (2013)'s conclusion that phytoliths do not
      abrade enamel" [J. Hum. Evol. 74 (2016) 130-133].

PMID- 27865440
TI  - Hemoglobin of 12 g/dl and above is not associated with increased cardiovascular
      morbidity in children on hemodialysis.
AB  - In adults on chronic hemodialysis, achieving a hemoglobin concentration of 12g/dl
      and above with erythropoiesis stimulating agents leads to increased
      cardiovascular events and mortality, but this may not be true in children.
      Therefore, we conducted a retrospective cohort study of pediatric patients (under
      18) from the Centers for Medicare and Medicaid Services End Stage Renal Disease
      (ESRD) Clinical Performance Measures (CPM) project (2000 to 2008) merged with the
      United States Renal Data System. Hemoglobin was determined from the Clinical
      Performance Measures data, and beginning annually on January 1st of the next
      year, patients were followed for up to 1 year. We determined the outcomes
      (mortality, hospitalization, and cardiovascular events) during follow-up by
      hemoglobin group at baseline. Models were adjusted for demographic and clinical
      characteristics of 1569 children studied. The hemoglobin 12 g/dl and above group
      was older, had fewer years of ESRD, and was more often transplanted. Inpatient
      and outpatient visits for congestive heart failure, cardiomyopathy, and valvular
      heart disease were most common in the hemoglobin under 10g/dl group and the
      frequency of these diagnoses decreased with increasing hemoglobin. The hazard
      ratio of all-cause mortality (0.33, 95% confidence interval 0.14-0.81) and the
      adjusted relative rate of all-cause hospitalizations (0.81, 0.74-0.89) were
      significantly lower in the hemoglobin 12 g/dl and above group. Cardiovascular
      hospitalizations were significantly higher in the hemoglobin under 10g/dl group
      (1.31, 1.05-1.64). Thus, in children on hemodialysis, hemoglobin 12g/dl and above
      is not associated with increased cardiovascular visits, mortality, or all-cause
      and cardiovascular-related hospitalizations.

PMID- 27865441
TI  - Long-term versus short-term dual antiplatelet therapy was similarly associated
      with a lower risk of death, stroke, or infarction in patients with acute coronary
      syndrome regardless of underlying kidney disease.
AB  - Scarce and conflicting evidence exists on whether clopidogrel is effective and
      whether dual antiplatelet treatment (DAPT) is safe in patients with acute
      coronary syndrome and chronic kidney disease (CKD). To study this, we performed
      an observational, prospective, multicenter cohort study of 36,001 patients of the
      SWEDEHEART registry. The exposure was DAPT prolonged after 3 months versus DAPT
      stopped at 3 months in consecutive patients with acute coronary syndrome and
      known serum creatinine. DAPT duration with clopidogrel and aspirin was assessed
      by dispensed tablets. CKD stages were classified according to estimated
      glomerular filtration rate (eGFR). Study outcomes were 1) the composite of death,
      myocardial infarction, or ischemic stroke; 2) bleeding; or 3) the aggregate of
      these two outcomes within day 111 and 365 from discharge. A longer DAPT duration,
      as compared with 3-month DAPT, was associated with lower hazard ratios for
      outcome one in each CKD stratum (eGFR over 60, adjusted hazard ratio [95%
      confidence interval] 0.76 [0.67-0.85]; eGFR 60 and less, 0.84 [0.73-0.96], of
      which eGFR between 45 and 60, 0.85 [0.70-1.05], eGFR between 30 and 45, 0.78
      [0.62-0.97]; eGFR 30 and less ml/min/1.73 m2, 0.93 [0.70-1.24]. Bleeding (outcome
      2) was in general more common in the longer DAPT group of each aforementioned CKD
      stratum. Aggregated outcome analysis (outcome 3) similarly favored longer DAPT in
      each stratum. There was no interaction between DAPT duration and CKD strata for
      any of the study outcomes. Thus, a prolonged as compared with three-month DAPT
      was similarly associated with a lower risk of death, stroke, or reinfarction
      regardless of underlying CKD.

PMID- 27865442
TI  - Triterpene glycosides from the aerial parts of Gouania longipetala.
AB  - Six previously undescribed triterpenoid saponins, gouaniaside I-VI, were isolated
      from the aerial parts of Gouania longipetala Hemsl. (Rhamnaceae), in addition to
      four known triterpenes. The structure elucidation of these compounds was based on
      analyses of spectroscopic data including 1D- and 2D-NMR and HR-ESI-MS techniques.
      The inhibitory activity of isolated compounds against promyelocytic leukemia HL60
      and human erythromyeloblastoid leukemia K562 cell lines was evaluated and
      jujuboside I exhibited moderate cytotoxicity, with IC50 values of 13.5 and 21.0
      MUM, respectively. Among the isolated triterpenes, alphitolic acid exhibited
      moderate antibacterial activity against Staphylococcus aureus, Enterococcus
      faecalis and Escherichia coli (MICs 32, 64 and 128 MUg/mL, respectively).

PMID- 27865443
TI  - Interaction of rare earth elements and components of the Horonobe deep
      groundwater.
AB  - To better understand the migration behavior of minor actinides in deep
      groundwater, the interactions between doped rare earth elements (REEs) and
      components of Horonobe deep groundwater were investigated. Approximately 10 ppb
      of the REEs, i.e. Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Er, Tm, and Yb were
      doped into a groundwater sample collected from a packed section in a borehole
      drilled at 140 m depth in the experiment drift of Horonobe Underground Research
      Laboratory in Hokkaido, Japan. The groundwater sample was sequentially filtered
      with a 0.2 MUm pore filter, and 10 kDa, 3 kDa and 1 kDa nominal molecular weight
      limit (NMWL) ultrafilters with conditions kept inert. Next, the filtrate
      solutions were analyzed with inductively coupled plasma mass spectrometry (ICP
      MS) to determine the concentrations of the REEs retained in solution at each
      filtration step, while the used filters were analyzed through neutron activation
      analysis (NAA) and TOF-SIMS element mapping to determine the amounts and chemical
      species of the trapped fractions of REEs on each filter. A strong relationship
      between the ratios of REEs retained in the filtrate solutions and the ionic radii
      of the associated REEs was observed; i.e. smaller REEs occur in larger
      proportions dissolved in the solution phase under the conditions of the Horonobe
      groundwater. The NAA and TOF-SIMS analyses revealed that portions of the REEs
      were trapped by the 0.2 MUm pore filter as REE phosphates, which correspond to
      the species predicted to be predominant by chemical equilibrium calculations for
      the conditions of the Horonobe groundwater. Additionally, small portions of
      colloidal REEs were trapped by the 10 kDa and 3 kDa NMWL ultrafilters. These
      results suggest that phosphate anions play an important role in the chemical
      behavior of REEs in saline (seawater-based) groundwater, which may be useful for
      predicting the migration behavior of trivalent actinides released from
      radioactive waste repositories in the far future.

PMID- 27865445
TI  - Perinatal complications of oocyte donation to women of advanced reproductive age.

PMID- 27865444
TI  - The Prospective Association of Organized Sports Participation With Cardiovascular
      Disease Risk in Children (the CHAMPS Study-DK).
AB  - OBJECTIVE: To investigate the prospective association of organized leisure-time
      sports participation with cardiovascular risk in children. METHODS: Students were
      recruited from 10 public primary schools. From July 2009 to October 2010, parents
      reported children's weekly organized leisure-time sports participation via text
      messaging. Clustered cardiovascular risk was estimated with a composite score
      comprising fasting serum triglyceride levels, homeostasis assessment model
      estimated insulin resistance, total to high-density lipoprotein cholesterol
      ratio, and systolic blood pressure. Additional outcomes were body mass index
      categories and fasting serum insulin and glucose concentrations. Associations
      were explored with generalized estimating equations and reported with beta
      coefficients (beta) and percent difference per weekly sports session or incidence
      rate ratios. All models were adjusted for baseline values and other potential
      confounders. RESULTS: In total, 1197 children (53% female) with a mean age of
      8.4+/-1.4 years were included. Participating in sports for 53 weeks was
      associated with lower clustered cardiovascular risk (beta, -0.25; 95% CI, -0.41
      to -0.10; percent difference, 3.2%; 95% CI, 5.2%-1.3%). Similar outcomes were
      observed for log homeostasis assessment model-estimated insulin resistance (beta,
      -0.08; 95% CI, -0.12 to -0.04; percent difference, 3.4%; 5.1%-1.7%) and log
      insulin (beta, -0.07; 95% CI, -0.11 to -0.04; percent difference, 2.6%; 95% CI,
      4.0%-1.5%). Sports participation was associated with a 20% decreased risk of
      overweight/obesity (incidence rate ratio, 0.78; 95% CI, 0.64-0.96). CONCLUSION:
      Participating in organized leisure-time sports for approximately 1 year is
      associated with decreased clustered cardiovascular risk in children. These
      findings show that participating in youth sports may be an effective strategy to
      reduce cardiovascular risk in children.

PMID- 27865446
TI  - Use of Utrogestan during controlled ovarian hyperstimulation in normally
      ovulating women undergoing in vitro fertilization or intracytoplasmic sperm
      injection treatments in combination with a "freeze all" strategy: a randomized
      controlled dose-finding study of 100 mg versus 200 mg.
AB  - OBJECTIVE: To compare the clinical characteristics in a Utrogestan and hMG
      protocol with the use of different doses of Utrogestan in normally ovulating
      women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection
      (ICSI) treatments. DESIGN: Prospective controlled study. SETTING: Tertiary-care
      academic medical center. PATIENT(S): A total of 150 infertile patients undergoing
      IVF/ICSI treatments. INTERVENTION(S): Utrogestan and hMG were administered
      simultaneously beginning on cycle day 3. The dose of Utrogestan was 100 mg/d in
      the study group and 200 mg/d in the control group. When the dominant follicles
      reached mature, 0.1 mg GnRH agonist was used for trigger. Viable embryos were
      cryopreserved in both protocols for later transfer. MAIN OUTCOME MEASURE(S): The
      primary outcome measure was the incidence of premature LH surge. Secondary
      outcomes included the embryo results and clinical pregnancy outcomes. RESULT(S):
      Consistent LH suppression was achieved during controlled ovarian hyperstimulation
      with Utrogestan at 100 mg, and the number of patients with profound LH
      suppression (LH <1.2 IU/L) in the low-dose group was significantly less than that
      in the high-dose group. The number of oocytes retrieved in the low-dose group was
      similar to that in the high-dose group (9.87 +/- 5.77 vs. 10.25 +/- 5.43). No
      significant differences were observed in the number of mature oocytes, viable
      embryos, clinical pregnancy rate, or implantation rate. CONCLUSION(S): Utrogestan
      at 100 mg is as effective as Utrogestan at 200 mg in reducing premature LH surge
      during controlled ovarian hyperstimulation. CLINICAL TRIAL REGISTRATION NUMBER:
      ChiCTR-OOC-14005277.

PMID- 27865447
TI  - Surgical management of niche, isthmocele, uteroperitoneal fistula, or cesarean
      scar defect: a critical rebirth in the medical literature.

PMID- 27865448
TI  - Debris makes "MR DC" hustle on endometriosis.

PMID- 27865449
TI  - Characterizing nuclear and mitochondrial DNA in spent embryo culture media:
      genetic contamination identified.
AB  - OBJECTIVE: To characterize nuclear and mitochondrial DNA (mtDNA) in spent culture
      media from normally developing blastocysts to determine whether it could be used
      for noninvasive genetic assessment. DESIGN: Prospective embryo cohort study.
      SETTING: Academic center and private in vitro fertilization (IVF) clinic.
      PATIENT(S): Seventy patients undergoing intracytoplasmic sperm injection (ICSI)
      and 227 blastocysts. INTERVENTION(S): Culture media assessment, artificial
      blastocoele fluid collapse and DNA analysis using digital polymerase chain
      reaction (dPCR), long-range PCR, quantitative PCR (qPCR), and DNA fingerprinting.
      MAIN OUTCOME MEASURE(S): Presence of nuclear and mtDNA in three different
      commercial culture media from Vitrolife and Irvine Scientific, spent embryo media
      assessment at the cleavage and blastocyst stages of development, and analysis of
      the internal media controls for each patient that had been exposed to identical
      conditions as embryo media but did not come into contact with embryos. RESULT(S):
      Higher levels of nuclear and mtDNA were observed in the culture media that had
      been exposed to embryos compared with the internal media controls. Nuclear DNA
      (~4 copies) and mtDNA (~600 copies) could be detected in spent media, and the
      levels increased at the blastocyst stage. No increase in DNA was detected after
      artificial blastocoele fluid collapse. Mixed sex chromosome DNA was detected.
      This originated from contamination in the culture media and from maternal
      (cumulus) cells. Due to the limited amount of template, the presence of embryonic
      nuclear DNA could not be confirmed by DNA fingerprinting analysis. CONCLUSION(S):
      Currently DNA from culture media cannot be used for genetic assessment because
      embryo-associated structures release DNA into the culture medium and the DNA is
      of mixed origin.

PMID- 27865450
TI  - Reproductive function in the sons of women who experienced stress due to
      bereavement before and during pregnancy: a nationwide population-based cohort
      study.
AB  - OBJECTIVE: To estimate the association between prenatal exposure to maternal
      stress and reproductive disorders in Danish men, where prenatal stress exposure
      was defined as the mother's loss of a close relative during pregnancy or in the
      12 months before conception. DESIGN: Population-based cohort study. SETTING: Not
      applicable. PATIENT(S): All males born in Denmark between 1973 and 2008 (n =
      1,217,576) and observed for up to 39 years. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Male reproductive function, defined using a composite outcome
      including congenital malformations of genital organs, testicular cancer,
      diagnosis of male infertility, or assisted conception use due to male factor
      infertility. RESULT(S): In total, 28,986 men (2.4%) had been exposed to prenatal
      stress, and 62,929 (5.2%) experienced the composite outcome during the follow-up
      period. Prenatal exposure to stress was associated with an elevated risk of
      reproductive problems (hazard ratio [HR] 1.09; 95% CI, 1.04-1.15). The
      association was stronger when the exposure occurred during the first trimester of
      pregnancy, and for congenital malformations of genital organs. When focusing on
      infertility alone, we saw no evidence of increased risk (HR 0.90; 95% CI, 0.77
      1.06). In addition, the probability of marrying a woman was lower for exposed men
      (HR 0.93; 95% CI, 0.89-0.98). CONCLUSION(S): Prenatal stress in the form of the
      mother's bereavement during the first trimester of pregnancy is associated with a
      higher risk of reproductive disorders from congenital malformations of the
      genital organs in the male offspring. The lack of an association between maternal
      bereavement and later infertility in the exposed male offspring may be due in
      part to the men's lower probability of attempting to have children.

PMID- 27865451
TI  - Astrocytic Contributions to Synaptic and Learning Abnormalities in a Mouse Model
      of Fragile X Syndrome.
AB  - BACKGROUND: Fragile X syndrome (FXS) is the most common type of mental
      retardation attributable to a single-gene mutation. It is caused by FMR1 gene
      silencing and the consequent loss of its protein product, fragile X mental
      retardation protein. Fmr1 global knockout (KO) mice recapitulate many behavioral
      and synaptic phenotypes associated with FXS. Abundant evidence suggests that
      astrocytes are important contributors to neurological diseases. This study
      investigates astrocytic contributions to the progression of synaptic
      abnormalities and learning impairments associated with FXS. METHODS: Taking
      advantage of the Cre-lox system, we generated and characterized mice in which
      fragile X mental retardation protein is selectively deleted or exclusively
      expressed in astrocytes. We performed in vivo two-photon imaging to track spine
      dynamics/morphology along dendrites of neurons in the motor cortex and examined
      associated behavioral defects. RESULTS: We found that adult astrocyte-specific
      Fmr1 KO mice displayed increased spine density in the motor cortex and impaired
      motor-skill learning. The learning defect coincided with a lack of enhanced spine
      dynamics in the motor cortex that normally occurs in response to motor skill
      acquisition. Although spine density was normal at 1 month of age in astrocyte
      specific Fmr1 KO mice, new spines formed at an elevated rate. Furthermore,
      fragile X mental retardation protein expression in only astrocytes was
      insufficient to rescue most spine or behavioral defects. CONCLUSIONS: Our work
      suggests a joint astrocytic-neuronal contribution to FXS pathogenesis and reveals
      that heightened spine formation during adolescence precedes the overabundance of
      spines and behavioral defects found in adult Fmr1 KO mice.

PMID- 27865452
TI  - CYP2A6 Genetic Variation Alters Striatal-Cingulate Circuits, Network Hubs, and
      Executive Processing in Smokers.
AB  - BACKGROUND: Variation in the CYP2A6 gene alters the rate of nicotine metabolic
      inactivation and is associated with smoking behaviors and cessation success
      rates. The underlying neurobiological mechanisms of this genetic influence are
      unknown. METHODS: Intrinsic functional connectivity strength, a whole-brain, data
      driven, graph theory-based method, was applied to resting-state functional
      magnetic resonance imaging data in 66 smokers and 92 nonsmokers. A subset of
      subjects (n = 23/20; smokers/nonsmokers) performed the monetary incentive delay
      task, probing reward anticipation, and a go/no-go task, probing response
      inhibition, on two occasions, in the presence and absence of a nicotine patch.
      RESULTS: A significant CYP2A6 genotype * smoking effect was found in the dorsal
      anterior cingulate cortex and ventral striatum, such that the normal (vs. slow)
      genotype individuals showed greater functional connectivity strength among
      smokers but not nonsmokers. Functional connectivity strength was negatively
      associated with severity of nicotine dependence in slow metabolizers. Both hubs
      were biased by inputs from the insula identified from seed-based connectivity.
      Similar gene * environment interactions were seen in ventral striatum during
      smoking abstinence when subjects performed the monetary incentive delay task and
      in dorsal anterior cingulate cortex when they performed the go/no-go task; both
      reductions were "normalized" in smokers (and increased in nonsmokers) after acute
      nicotine administration. CONCLUSIONS: Because the CYP2A6 effect was seen only in
      smokers, these data suggest that the rate of nicotine metabolism-and thus the
      concentration of nicotine presented to the brain over the course of nicotine
      addiction-shapes brain circuits that, among other functions, compute reward and
      impulsivity processes.

PMID- 27865454
TI  - Does a groin node dissection in vulvar cancer affect groin recurrence and overall
      survival?: Results from a population-based cohort study.
AB  - BACKGROUND: To determine, in a population-based cohort of vulvar cancer patients,
      if groin node dissection (GND) decreases the risk of groin recurrence and
      increases overall survival. METHODS: This population-based retrospective cohort
      study includes all cases of invasive squamous cell carcinoma identified in a
      provincial cancer registry from 1998 to 2007. Data collection was completed for
      all clinical and pathologic factors by chart abstraction. Cumulative incidence
      functions for recurrence were estimated, accounting for death before recurrence
      as a competing risk. Multivariable Cox regression models examined the
      associations between GND and groin recurrence, and overall survival. RESULTS:
      Clinical and pathologic data were collected for 1109 patients, of which 1038
      patients were eligible for GND. 647 patients (62%) had a GND, while 391 patients
      (38%) did not. Median follow-up was 2.8years. Cumulative incidence plots
      demonstrate that the risk of death without recurrence was consistently higher
      than groin recurrence in each year after diagnosis. On multivariate analysis, GND
      was not significantly associated with decreased groin recurrence (HR 0.91, 95% CI
      0.58-1.44, p=0.70). The hazard of death was 15% lower for women who received GND
      (HR 0.85, 95% CI 0.63-1.16, p=0.32), but this difference was not statistically
      significant. CONCLUSIONS: There was no significant difference in groin recurrence
      or overall survival in those with or without GND in this population-based cohort,
      raising questions whether a subgroup of patients may not benefit from GND.
      Patients had a higher probability of dying before groin recurrence could occur.
      Future trial design should consider death as a competing risk.

PMID- 27865455
TI  - Analysis of ustiloxins in rice using polymer cation exchange cleanup followed by
      liquid chromatography-tandem mass spectrometry.
AB  - Ustiloxins are cyclopeptide mycotoxins produced by the pathogenic fungus
      Ustilaginoidea virens of rice false smut. Quantification of ustiloxins is
      essential to assess the food safety of rice infected by rice false smut disease.
      This paper describes a sensitive method for the simultaneous quantification of
      ustiloxins A, B, C, D and F in rice grains using liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). Since notable matrix enhancement effects (21%-78%)
      occurred for all of the target analytes (except for ustiloxin A), several solid
      phase extraction materials were tested for their ability to retain ustiloxins
      from aqueous solutions prior to the LC-MS/MS analysis, including C18 sorbents,
      polymer anion exchange sorbents resin (PAX), and polymer cation exchange resin
      (PCX). The PCX resin was adopted due to its higher extraction capability and
      selectivity for all targets compared to others, and in this case, almost no
      matrix effects (-5% to 8%) were observed for all of the ustiloxins monitored. The
      developed method reached limits of quantification of 0.2-2ngg-1, and linearity
      was statistically verified over two orders of magnitude with regression
      coefficients (R2)>0.991. The mean recoveries were from 85% to 109%, and the inter
      day precisions (n=11) were less than 16%, with intra-day precisions (n=6) within
      12%. Analysis of samples showed that ustiloxin A was the dominant species, with
      the content ranging from 5.5 to 273.8ngg-1, followed by ustiloxin B (<=88.7ngg
      1), while concentrations of ustiloxins C, D and F were slightly lower (<=43.2ngg
      1). To our knowledge, this is the first report on the determination and analysis
      of five ustiloxins simultaneously in a single analysis.

PMID- 27865453
TI  - Neurophysiology and Regulation of the Balance Between Excitation and Inhibition
      in Neocortical Circuits.
AB  - Brain function relies on the ability of neural networks to maintain stable levels
      of activity, while experiences sculpt them. In the neocortex, the balance between
      activity and stability relies on the coregulation of excitatory and inhibitory
      inputs onto principal neurons. Shifts of excitation or inhibition result in
      altered excitability impaired processing of incoming information. In many
      neurodevelopmental and neuropsychiatric disorders, the excitability of local
      circuits is altered, suggesting that their pathophysiology may involve shifts in
      synaptic excitation, inhibition, or both. Most studies focused on identifying the
      cellular and molecular mechanisms controlling network excitability to assess
      whether they may be altered in animal models of disease. The impact of changes in
      excitation/inhibition balance on local circuit and network computations is not
      clear. Here we report findings on the integration of excitatory and inhibitory
      inputs in healthy cortical circuits and discuss how shifts in
      excitation/inhibition balance may relate to pathological phenotypes.

PMID- 27865456
TI  - Selective adsorption of flavor-active components on hydrophobic resins.
AB  - This work aims to propose an optimum resin that can be used in industrial
      adsorption process for tuning flavor-active components or removal of ethanol for
      producing an alcohol-free beer. A procedure is reported for selective adsorption
      of volatile aroma components from water/ethanol mixtures on synthetic hydrophobic
      resins. High throughput 96-well microtiter-plates batch uptake experimentation is
      applied for screening resins for adsorption of esters (i.e. isoamyl acetate, and
      ethyl acetate), higher alcohols (i.e. isoamyl alcohol and isobutyl alcohol), a
      diketone (diacetyl) and ethanol. The miniaturized batch uptake method is adapted
      for adsorption of volatile components, and validated with column breakthrough
      analysis. The results of single-component adsorption tests on Sepabeads SP20-SS
      are expressed in single-component Langmuir, Freundlich, and Sips isotherm models
      and multi-component versions of Langmuir and Sips models are applied for
      expressing multi-component adsorption results obtained on several tested resins.
      The adsorption parameters are regressed and the selectivity over ethanol is
      calculated for each tested component and tested resin. Resin scores for four
      different scenarios of selective adsorption of esters, higher alcohols, diacetyl,
      and ethanol are obtained. The optimal resin for adsorption of esters is Sepabeads
      SP20-SS with resin score of 87% and for selective removal of higher alcohols,
      XAD16N, and XAD4 from Amberlite resin series are proposed with scores of 80 and
      74% respectively. For adsorption of diacetyl, XAD16N and XAD4 resins with score
      of 86% are the optimum choice and Sepabeads SP2MGS and XAD761 resins showed the
      highest affinity towards ethanol.

PMID- 27865457
TI  - Viral Carcinogenesis.
AB  - Cancer has been recognized for thousands of years. Egyptians believed that cancer
      occurred at the will of the gods. Hippocrates believed human disease resulted
      from an imbalance of the four humors: blood, phlegm, yellow bile, and black bile
      with cancer being caused by excess black bile. The lymph theory of cancer
      replaced the humoral theory and the blastema theory replaced the lymph theory.
      Rudolph Virchow was the first to recognize that cancer cells like all cells came
      from other cells and believed chronic irritation caused cancer. At the same time
      there was a belief that trauma caused cancer, though it never evolved after many
      experiments inducing trauma. The birth of virology occurred in 1892 when Dimitri
      Ivanofsky demonstrated that diseased tobacco plants remained infective after
      filtering their sap through a filter that trapped bacteria. Martinus Beijerinck
      would call the tiny infective agent a virus and both Dimitri Ivanofsky and
      Marinus Beijerinck would become the fathers of virology. Not to long thereafter,
      Payton Rous founded the field of tumor virology in 1911 with his discovery of a
      transmittable sarcoma of chickens by what would come to be called Rous sarcoma
      virus or RSV for short. The first identified human tumor virus was the Epstein
      Barr virus (EBV), named after Tony Epstein and Yvonne Barr who visualized the
      virus particles in Burkitt's lymphoma cells by electron microscopy in 1965. Since
      that time, many viruses have been associated with carcinogenesis including the
      most studied, human papilloma virus associated with cervical carcinoma, many
      other anogenital carcinomas, and oropharyngeal carcinoma. The World Health
      Organization currently estimates that approximately 22% of worldwide cancers are
      attributable to infectious etiologies, of which viral etiologies is estimated at
      15-20%. The field of tumor virology/viral carcinogenesis has not only identified
      viruses as etiologic agents of human cancers, but has also given molecular
      insights to all human cancers including the oncogene activation and tumor
      suppressor gene inactivation.

PMID- 27865460
TI  - Current and Emerging Targeting Strategies for Treatment of Pancreatic Cancer.
AB  - With a dismal 5-year survival rate of only 8%, pancreatic cancer still remains a
      very lethal disease. As with most cancers, pancreatic cancer is treated with
      different combinations of chemotherapeutic drugs which result in side effects and
      potential drug resistance leading in many cases to the unfortunate demise of the
      patient. Over recent years, a number of therapies have been developed against
      numerous molecular targets in cancers. Kinase inhibitors and monoclonal
      antibodies have been shown to target numerous kinases, growth factor receptors,
      and cell signaling pathways. This can lead to effects on tumor cell growth,
      angiogenesis, apoptosis, and the microenvironment. Most recent findings are very
      promising as they relate to the use of immunotherapy to treat certain cancers.
      Immune checkpoint inhibitors and cancer vaccines are currently being
      investigated. In this review, we will highlight some novel molecular targeted
      strategies that are being used or considered as potential therapeutics to treat
      patients with pancreatic cancer.

PMID- 27865461
TI  - Molecular and Cellular Changes During Cancer Progression Resulting From Genetic
      and Epigenetic Alterations.
AB  - Tumorigenesis is a complex process that involves a persistent dismantling of
      cellular safeguards and checkpoints. These molecular and cellular changes that
      accumulate over months or decades lead to a change in the fundamental identity of
      a cell as it transitions from normal to malignant. In this chapter, we will
      examine some of the molecular changes in the evolving relationship between the
      genome and epigenome and highlight some of the key changes that occur as normal
      cells progress to tumor cells. For many years tumorigenesis was almost
      exclusively attributed to mutations in protein-coding genes. This notion that
      mutations in protein-coding genes were a fundamental driver of tumorigenesis
      enabled the development of several novel therapeutics that targeted the mutant
      protein or overactive pathway responsible for driving a significant portion of
      the tumor growth. However, because many therapeutic challenges remained in the
      face of these advances, it was clear that other pieces to the puzzle had yet to
      be discovered. Advances in molecular and genomics techniques continued and the
      study of epigenetics began to expand and helped reshape the view that drivers of
      tumorigenesis extended beyond mutations in protein-coding genes. Studies in the
      field of epigenetics began to identify aberrant epigenetic marks which created
      altered chromatin structures and enabled protein expression in tissues that
      defied rules governing tissue-specificity. Not only were epigenetic alterations
      found to enable overexpression of proto-oncogenes, they also led to the silencing
      of tumor suppressor genes. With these discoveries, it became clear that tumor
      growth could be stimulated by much more than mutations in protein-coding genes.
      In fact, it became increasingly clear that much of the human genome, while
      transcribed, did not lead to proteins. This discovery further led to studies that
      began to uncover the role of noncoding RNAs in regulating chromatin structure,
      gene transcription, and tumor biology. In this chapter, some of the key
      alterations in the genome and epigenome will be explored, and some of the cancer
      therapies that were developed as a result of these discoveries will be discussed.

PMID- 27865462
TI  - Molecular Changes Associated With Tumor Initiation and Progression of Soft Tissue
      Sarcomas: Targeting the Genome and Epigenome.
AB  - Soft tissue sarcomas are rare, but generally aggressive tumors which
      disproportionately affect children and young adults. They represent less than 10%
      of all cancers, but are one of the most frequently diagnosed cancers in pediatric
      patients. These cancers have a high rate of morbidity and mortality, and their
      overall incidence has been increasing at an estimated rate of 26% over the last 2
      decades. The cause of this increased incidence is unknown but various
      environmental factors have been implicated. Establishing standard therapeutic
      strategies is challenging for soft tissue sarcomas as more than 50 different
      histological subtypes exist, each with their own molecular alterations and
      clinical characteristics, and this combination of tumor heterogeneity and a
      limited number of clinical cases make detailed omics level molecular studies
      particularly challenging. This chapter will focus on the unique genetic and
      epigenetic changes which characterize these cancers, with an emphasis on
      translocation-associated sarcomas involving primary gene fusions with the RNA
      chaperone protein EWSR1. We will highlight current therapeutic approaches and
      discuss opportunities for targeted molecular therapeutics.

PMID- 27865463
TI  - Molecular Changes During Acute Myeloid Leukemia (AML) Evolution and
      Identification of Novel Treatment Strategies Through Molecular Stratification.
AB  - Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by
      impaired differentiation and uncontrollable proliferation of myeloid progenitor
      cells. Due to high relapse rates, overall survival for this rapidly progressing
      disease is poor. The significant challenge in AML treatment is disease
      heterogeneity stemming from variability in maturation state of leukemic cells of
      origin, genetic aberrations among patients, and existence of multiple disease
      clones within a single patient. Disease heterogeneity and the lack of biomarkers
      for drug sensitivity lie at the root of treatment failure as well as selective
      efficacy of AML chemotherapies and the emergence of drug resistance. Furthermore,
      standard-of-care treatment is aggressive, presenting significant tolerability
      concerns to the commonly advanced-age AML patient. In this review, we examine the
      concept and potential of molecular stratification, particularly with biologically
      relevant drug responses, in identifying low-toxicity precision therapeutic
      combinations and clinically relevant biomarkers for AML patient care as a way to
      overcome these challenges in AML treatment.

PMID- 27865459
TI  - Molecular Pathogenesis of Pancreatic Cancer.
AB  - Pancreatic cancers arise predominantly from ductal epithelial cells of the
      exocrine pancreas and are of the ductal adenocarcinoma histological subtype
      (PDAC). PDAC is an aggressive disease associated with a poor clinical prognosis,
      weakly effective therapeutic options, and a lack of early detection methods.
      Furthermore, the genetic and phenotypic heterogeneity of PDAC complicates efforts
      to identify universally efficacious therapies. PDACs commonly harbor activating
      mutations in the KRAS oncogene, which is a potent driver of tumor initiation and
      maintenance. Inactivating mutations in tumor suppressor genes such as CDKN2A/p16,
      TP53, and SMAD4 cooperate with KRAS mutations to cause aggressive PDAC tumor
      growth. PDAC can be classified into 3-4 molecular subtypes by global gene
      expression profiling. These subtypes can be distinguished by distinct molecular
      and phenotypic characteristics. This chapter will provide an overview of the
      current knowledge of PDAC pathogenesis at the genetic and molecular level as well
      as novel therapeutic opportunities to treat this highly aggressive disease.

PMID- 27865464
TI  - Myeloproliferative Neoplasms: Molecular Drivers and Therapeutics.
AB  - Activating mutations in genes that drive neoplastic cell growth are numerous and
      widespread in cancer, and specific genetic alterations are associated with
      certain types of cancer. For example, classic myeloproliferative neoplasms (MPNs)
      are hematopoietic stem cell disorders that affect cells of the myeloid lineage,
      including erythrocytes, platelets, and granulocytes. An activating mutation in
      the JAK2 tyrosine kinase is prevalent in these diseases. In MPN patients that
      lack such a mutation, other genetic changes that lead to activation of the JAK2
      signaling pathway are present, indicating deregulation of JAK2 signaling plays an
      etiological driving role in MPNs, a concept supported by significant evidence
      from in vivo experimental MPN systems. Thus, small molecules that inhibit JAK2
      activity are ideal drugs to impede the progression of disease in MPN patients.
      However, even though JAK inhibitors provide significant symptomatic relief, they
      have failed as a remission-inducing therapy. Nonetheless, the progress made
      understanding the molecular etiology of MPNs since 2005 is significant and has
      provided insight for the development and testing of novel molecular targeted
      therapeutic approaches. The current understanding of driver mutations in MPNs and
      an overview of current and potential therapeutic strategies for MPN patients will
      be discussed.

PMID- 27865465
TI  - Dysregulation of Aromatase in Breast, Endometrial, and Ovarian Cancers: An
      Overview of Therapeutic Strategies.
AB  - Aromatase is the rate-limiting enzyme in the biosynthesis of estrogens, which
      play crucial roles on a spectrum of developmental and physiological processes.
      The biological actions of estrogens are classically mediated by binding to two
      estrogen receptors (ERs), ERalpha and ERbeta. Encoded by the cytochrome P450,
      family 19, subfamily A, polypeptide 1 (CYP19A1) gene, aromatase is expressed in a
      wide variety of tissues, as well as benign and malignant tumors, and is regulated
      in a pathway- and tissue-specific manner. Overexpression of aromatase, leading to
      elevated systemic levels of estrogen, is unequivocally linked to the pathogenesis
      and growth of a number malignancies, including breast, endometrium, and ovarian
      cancers. Aromatase inhibitors (AIs) are routinely used to treat estrogen
      dependent breast cancers in postmenopausal women; however, their roles in
      endometrial and ovarian cancers remain obscure. While AI therapy is effective in
      hormone sensitive cancers, they diminish estrogen production throughout the body
      and, thus, generate undesirable side effects. Despite the effectiveness of AI
      therapy, resistance to endocrine therapy remains a major concern and is the
      leading cause of cancer death. Considerable advances, toward mitigating these
      issues, have evolved in conjunction with a number of histone deacetylase (HDAC)
      inhibitors for countering an assortment of diseases and cancers, including the
      aforesaid malignancies. HDACs are a family of enzymes that are frequently
      dysregulated in human tumors. This chapter will discuss the current understanding
      of aberrant regulation and expression of aromatase in breast, endometrial, and
      ovarian cancers, and potential therapeutic strategies for prevention and
      treatment of these life-threatening diseases.

PMID- 27865466
TI  - Wnt/beta Catenin-Mediated Signaling Commonly Altered in Colorectal Cancer.
AB  - Colorectal cancer is the second most common cancer in females and the third most
      common cancer diagnosed in males (Torre et al.1). In 2012, there were about 1.4
      million cases and 693,900 deaths due to colorectal cancer worldwide. It is more
      common in developed countries, and North America, Europe, and Australia have the
      highest incidence rates. In the United States, adults have a 5% chance of
      developing colorectal cancer (Cancer of the colon and rectum-SEER stat fact
      sheets2). Due to the high prevalence of colorectal cancer, understanding the
      mechanism underlying its initiation and progression in order to find better
      therapeutic agents will have a high impact in the field of oncology and may
      improve the treatment of other cancers with shared mechanistic properties.
      Aberrant Wnt/beta-catenin signaling is a characteristic feature of colorectal
      cancer development and is the focus of this review.

PMID- 27865467
TI  - Molecular Changes During Breast Cancer and Mechanisms of Endocrine Therapy
      Resistance.
AB  - Estrogen receptors (ERs) are expressed in 75% of breast cancers. ERs and their
      estrogen ligands play a key role in the development and progression of breast
      cancer. ERs have a genomic activity involving direct modulation of expression of
      genes vital to cell growth and survival by their classic nuclear receptors. The
      nongenomic activity is mediated by membrane receptor tyrosine kinases that
      activate signaling pathways resulting in activation of ER pathway modulators.
      Endocrine therapies inhibit the growth promoting activity of estrogen. ERs
      positive breast cancers can exhibit de novo or acquired endocrine resistance. The
      mechanisms of endocrine therapy resistance are complex include deregulation of ER
      pathway, growth factor receptor signaling, cell cycle machinery, and tumor
      microenvironment. In this chapter, we will review the literature on the biology
      of ERs, the postulated mechanisms of endocrine therapy resistance, and their
      clinical implications.

PMID- 27865468
TI  - Molecular and Cellular Changes in Breast Cancer and New Roles of lncRNAs in
      Breast Cancer Initiation and Progression.
AB  - Breast cancer is not just one disease but many variations on a theme, comprising
      a variety of molecular subtypes with distinct etiologies, cellular origins,
      treatment strategies, and prognoses. Like mRNAs and microRNAs (miRNAs), long
      noncoding RNAs (lncRNAs) differ dramatically in expression across breast cancer
      subtypes and can be used for classification. While there has been considerable
      emphasis on miRNAs, our knowledge is still in its infancy about the role of
      lncRNAs that comprise the majority of the mammalian transcriptome. In this
      chapter, we will review the critical functions that lncRNAs play in breast cancer
      development and metastatic progression. We will conclude with a discussion of
      current and future approaches for RNA-targeted therapeutic intervention.

PMID- 27865469
TI  - Interplay Between Inflammation and Epigenetic Changes in Cancer.
AB  - Immune responses can suppress tumorigenesis, but also contribute to cancer
      initiation and progression suggesting a complex interaction between the immune
      system and cancer. Epigenetic alterations, which are heritable changes in gene
      expression without changes to the DNA sequence, also play a role in
      carcinogenesis through silencing expression of tumor suppressor genes and
      activating oncogenic signaling. Interestingly, epithelial cells at sites of
      chronic inflammation undergo DNA methylation alterations that are similar to
      those present in cancer cells, suggesting that inflammation may initiate cancer
      specific epigenetic changes in epithelial cells. Furthermore, epigenetic changes
      occur during immune cell differentiation and participate in regulating the immune
      response, including the regulation of inflammatory cytokines. Cancer cells
      utilize epigenetic silencing of immune-related genes to evade the immune
      response. This chapter will detail the interactions between inflammation and
      epigenetics in tumor initiation, promotion, and immune evasion and how these
      connections are being leveraged in cancer prevention and treatment.

PMID- 27865470
TI  - Preface.

PMID- 27865471
TI  - Satisfaction and treatment adherence in erectile dysfunction in the medium and
      long term.
AB  - INTRODUCTION: The aim of this study was to show the satisfaction and treatment
      adherence in erectile dysfunction (ED) in the medium and long term. MATERIAL AND
      METHODS: A descriptive, comparative study was conducted in 2 centres through
      telephone interviews with patients who came for an initial visit between 2012 and
      2014 for ED. A complete case history review was conducted on the use of and
      withdrawal from treatment. For current use, the Erectile Dysfunction Inventory of
      Treatment Satisfaction (EDITS) and the Global Assessment Questionnaire (GAQ) were
      filled out; for past use, only the GAQ was filled out. For the statistical
      analysis, we employed Fisher's exact test for comparisons of percentages and the
      Kruskal-Wallis test to compare means. RESULTS: The study included 250 patients;
      20.8% were prescribed intraurethral alprostadil (ALP-IU), 17.2% were prescribed
      intracavernous alprostadil (ALP-IC), 92.8% were prescribed a first IPD5, and
      24.8% were prescribed at least a second IPD5. The treatment withdrawal rate was
      62.07% for the first IPD5, 41.94% for the last IPD5, 69.23% for the ALP-IU and
      65.11% for the ALP-IC (P=.007). The main reason for withdrawal for the IPD5 was a
      lack of response (32.76% of those who took IPD5). In addition to withdrawal,
      there were adverse reactions for ALP-IU and ALP-IC (28.85% and 11.63%,
      respectively). The mean duration of use until withdrawal was 4.3 months for IPD5,
      2.2 months for ALP-IU and 5.5 months for ALP-IC (P=.064). The most favourable GAQ
      and EDITS scores were observed for IPD5 (EDITS score of 74). Sildenafil and
      tadalafil had the longest usage times (mean >5 months). CONCLUSIONS: The
      withdrawal rate for treating ED is high, with short usage times of a few months.
      A lack of response and adverse reactions were the main causes for withdrawal. The
      drugs that provide greater satisfaction are the IPD5, although there are no
      significant differences in the mean usage time between the different types and in
      aspects such as the mean usage time to withdrawal or the withdrawal rates.

PMID- 27865472
TI  - Taking a STEP back: Assessing the outcomes of multiple STEP procedures.
AB  - PURPOSE: Short bowel syndrome (SBS) is a highly morbid condition primarily
      because of parenteral nutrition (PN)-associated complications. Bowel lengthening
      via serial transverse enteroplasty (STEP) has become standard of care. While
      initial STEPs have resulted in weaning from PN, outcomes of repeated STEPs
      (ReSTEPs) are not well described. We investigated outcomes of initial STEP
      compared to ReSTEP procedures. METHODS: This retrospective review of STEPs
      included 17 children and a total of 24 procedures. Demographics, complications,
      hospital readmission rates, postoperative costs, and PN weaning were analyzed.
      RESULTS: Neither patient-specific data nor the etiology of SBS was predictive of
      requiring a ReSTEP. PN weaning was more likely in the year following a first STEP
      (18% wean rate vs. 0% for ReSTEP, p>.05). No ReSTEP patients reached enteral
      autonomy. Enteral nutrition (%EN) increases were greater after first STEP
      compared to ReSTEP (26.0% vs. 4.7%, p=0.03). This trend was true for bowel length
      as well, where first STEPs resulted in a 51% increase in bowel length compared to
      a 20% increase after in ReSTEP (p=0.02). CONCLUSIONS: ReSTEPs failed to result in
      significant PN weaning, with no ReSTEP patients achieving enteral autonomy during
      follow-up. Given its higher costs, smaller bowel length gains, and limited
      ability to produce enteral autonomy, surgeons should carefully consider
      performing ReSTEP procedures. LEVEL OF EVIDENCE: Level III.

PMID- 27865473
TI  - Automated data extraction: merging clinical care with real-time cohort-specific
      research and quality improvement data.
AB  - BACKGROUND/PURPOSE: Although prohibitively labor intensive, manual data
      extraction (MDE) is the prevailing method used to obtain clinical research and
      quality improvement (QI) data. Automated data extraction (ADE) offers a powerful
      alternative. The purposes of this study were to 1) assess the feasibility of ADE
      from provider-authored outpatient documentation, and 2) evaluate the
      effectiveness of ADE compared to MDE. METHODS: A prospective collection of data
      was performed on 90 ADE-templated notes (N=71 patients) evaluated in our bowel
      management clinic. ADE captured data were compared to 59 MDE notes (N=51)
      collected under an IRB-exempt review. Sixteen variables were directly comparable
      between ADE and MDE. RESULTS: MDE for 59 clinic notes (27 unique variables) took
      6months to complete. ADE-templated notes for 90 clinic notes (154 unique
      variables) took 5min to run a research/QI report. Implementation of ADE included
      eight weeks of development and testing. Pre-implementation clinical documentation
      was similar to post-implementation documentation (5-10min). CONCLUSIONS: ADE
      templated notes allow for a 5-fold increase in clinically relevant data that can
      be captured with each encounter. ADE also results in real-time data extraction to
      a research/QI database that is easily queried. The immediate availability of
      these data, in a research-formatted spreadsheet, allows for rapid collection,
      analyses, and interpretation of the data. LEVEL OF EVIDENCE: IV. TYPE OF STUDY:
      Retrospective Study.

PMID- 27865474
TI  - Tubeless Uniportal Thoracoscopic Wedge Resection for Peripheral Lung Nodules.
AB  - BACKGROUND: Endotracheal intubation and chest tube drainage are considered
      mandatory for thoracoscopic pulmonary resection. The management of peripheral
      lung nodules by tubeless uniportal thoracoscopic surgical repair has not been
      reported previously. METHODS: From October 2015 through January 2016, 30
      consecutive patients with peripheral lung nodules underwent uniportal
      thoracoscopic wedge resection without endotracheal intubation and chest tube
      drainage (tubeless group). The clinical outcomes were compared with the outcomes
      in 30 consecutive patients with peripheral lung nodules who underwent uniportal
      thoracoscopic wedge resection with chest tube drainage from April through October
      2015 (chest tube group). RESULTS: The demographic, anesthetic, and operative
      characteristics of the patients were comparable in both groups. No major adverse
      events occurred after operation. A small residual pneumothorax was noted in 12
      (40.0%) patients at 6 hours and day 1 and in 2 (6.6%) patients on day 14 in the
      tubeless group. No patient required reintervention or readmission to the
      hospital. Patients in the tubeless group had lower pain scale scores on
      postoperative day 1 (mean, 1.0 vs 1.5, p = 0.012) and shorter postoperative
      hospital stays (mean, 3.1 days vs 4.4 days, p = 0.011) than did those in the
      chest tube group. CONCLUSIONS: Tubeless uniportal thoracoscopic wedge resection
      is feasible and safe and may be a less invasive alternative for treating selected
      patients with peripheral lung nodules.

PMID- 27865476
TI  - Endobronchial and Endoscopic Ultrasound-Guided Transvascular Biopsy of
      Mediastinal, Hilar, and Lung Lesions.
AB  - BACKGROUND: Endoscopic techniques, including endobronchial ultrasound (EBUS) and
      endoscopic ultrasound (EUS), are the initial approach for the diagnosis and
      staging of lung cancer and the diagnosis of mediastinal and hilar lesions.
      Historically, the transvascular approach has been avoided because of concerns of
      bleeding. Here we review our experience with EBUS and EUS transvascular biopsy of
      mediastinal, hilar, and lung lesions. METHODS: A prospective research database
      was used to retrospectively identify and review the records 33 consecutive
      patients who underwent EBUS and EUS transvascular biopsy in an outpatient setting
      over 4 years. Complications were identified as significant hematoma seen with
      endoscopic ultrasound, hemothorax, hemoptysis other than minor, hemodynamic
      instability, hospital admission, and death. RESULTS: The biopsies in 14 patients
      were performed through branches of the pulmonary artery, and 19 were done through
      the aorta. All EUS biopsies were performed with a 22-gauge needle, and all EBUS
      biopsies were performed with a 21-gauge needle. Malignancy was diagnosed with
      specimens from a transvascular biopsy in 16 patients (48.5%). Samples from 8
      biopsies (24%) were described as negative for malignancy, and 9 specimens (27%)
      were described as insufficient. No complications were seen in the immediate
      postprocedural period, and all 33 patients were discharged home the same day. The
      median follow-up after the procedure was 12 months, with no complications
      described. The overall yield was 73%. CONCLUSIONS: In this series, EBUS- and EUS
      guided transvascular approach for biopsy of mediastinal, hilar, and lung lesions
      was not associated with significant complications. However, careful selection of
      potential candidates and close periprocedural observation are mandatory.

PMID- 27865475
TI  - Soluble Receptor for Advanced Glycation End Products Quantifies Lung Injury in
      Polytraumatized Patients.
AB  - BACKGROUND: Biomarkers caused by blunt chest trauma might leak into the vascular
      compartment and therefore reflect the severity of parenchymal lung injury (PLI).
      Five promising proteins were preselected after a literature scan. The objective
      of our study was to identify a biomarker that is released abundantly into the
      serum shortly after trauma and reliably quantifies the loss of functional lung
      tissue. METHODS: Polytraumatized patients (aged >=18 years, Injury Severity Score
      [ISS] >=16) were included in our prospective observational study if they were
      admitted directly to our level I trauma center during the first hour after trauma
      occurred. Immediately after stabilizing the patient's condition, blood samples
      were taken and a whole-body computed tomographic (CT) scan was obtained.
      Biomarker levels were measured directly after admission and on day 2. PLI volume
      was calculated using volumetric analysis. RESULTS: One hundred thirty patients
      met the inclusion criteria. Compared with a matched healthy control population,
      median levels of the soluble receptor for advanced glycation end products (sRAGE)
      was almost 3 times higher and decreased by 41% on day 2. Higher initial median
      sRAGE levels were detected in patients with PLI compared with patients without
      PLI and in individuals with severe PLI compared with those with mild PLI.
      Spearman correlation analysis and a univariate linear log regression model
      revealed a significant correlation/equation between initial sRAGE levels and
      relative PLI volume. Receiver operating characteristic (ROC) statistics
      identified the initial sRAGE level as an indicator of severe PLI. CONCLUSIONS:
      sRAGE levels measured shortly after trauma seem to be a promising diagnostic tool
      to assess the severity of PLI in polytraumatized patients.

PMID- 27865458
TI  - The Interaction Between Human Papillomaviruses and the Stromal Microenvironment.
AB  - Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that
      replicate in stratified squamous epithelia and cause a variety of malignancies.
      Current efforts in HPV biology are focused on understanding the virus-host
      interactions that enable HPV to persist for years or decades in the tissue. The
      importance of interactions between tumor cells and the stromal microenvironment
      has become increasingly apparent in recent years, but how stromal interactions
      impact the normal, benign life cycle of HPVs, or progression of lesions to cancer
      is less understood. Furthermore, how productively replicating HPV impacts cells
      in the stromal environment is also unclear. Here we bring together some of the
      relevant literature on keratinocyte-stromal interactions and their impacts on HPV
      biology, focusing on stromal fibroblasts, immune cells, and endothelial cells. We
      discuss how HPV oncogenes in infected cells manipulate other cells in their
      environment, and, conversely, how neighboring cells may impact the efficiency or
      course of HPV infection.

PMID- 27865477
TI  - Tracheostomy Among Infants With Hypoplastic Left Heart Syndrome Undergoing
      Cardiac Operations: A Multicenter Analysis.
AB  - BACKGROUND: Less than 2.7% of infants undergoing congenital heart disease
      operations have difficulty weaning from invasive mechanical ventilation. In such
      instances, clinicians may choose to perform tracheostomy. Limited literature has
      examined tracheostomy placement specifically in infants with hypoplastic left
      heart syndrome (HLHS). This study evaluated the risk factors for tracheostomy
      placement in infants with HLHS and examined the outcomes of these infants before
      their first hospital discharge. METHODS: This retrospective analysis of the
      Pediatric Heath Information System data set included infants with HLHS who
      underwent stage 1 Norwood operation, a hybrid procedure, or heart transplant from
      2004 through 2013. RESULTS: We identified 5721 infants with HLHS, and 126
      underwent tracheostomy placement. Infants in the tracheostomy group had more
      morbidities and a higher mortality rate across the study period. Diagnosis of
      chromosomal abnormalities, anomalies of the trachea and esophagus, larynx,
      diaphragm and nervous system, bilateral vocal cord paralysis, and necrotizing
      enterocolitis, and procedures including extracorporeal membrane oxygenation
      support, cardiac catheterization, and gastrostomy tube were independently
      associated with tracheostomy placement in the study population. Despite an
      overall increase in rates of tracheostomy performed in infants with HLHS during
      the study period, the mortality rate did not improve among tracheostomy patients.
      CONCLUSIONS: Several risk factors were identified in infants with HLHS in whom a
      tracheostomy was placed during their first hospitalization. Despite an overall
      increase in rates of tracheostomies during the study period, the mortality rate
      did not improve among these patients. Appropriate family counseling and thorough
      preoperative case selection is suggested when discussing possible tracheostomy
      placement in infants with HLHS.

PMID- 27865478
TI  - The limits of stability and muscle activity in middle-aged adults during static
      and dynamic stance.
AB  - Balance control plays an important role in maintaining daily activity. However,
      studies on postural control among middle-aged adults are scarce. This study aims
      (i) to examine directional control (DCL) and electromyography activity (EMG) for
      different stability levels, and (ii) to determine left-right asymmetry for DCL
      and muscle activity among sedentary middle-aged adults. Twenty healthy, middle
      aged adults (10 males, 10 females; age=50.0+/-7.5yrs; body height: 1.61+/-0.10m;
      body mass: 70.0+/-14.5kg) participated in the study. EMG for left and right side
      of rectus femoris (RF), biceps femoris (BF), and medial gastrocnemius (MG) were
      recorded. Two-way repeated measures analysis of variance was used to assess the
      effect of dynamic level on DCL and EMG, whereas independent sample t-test was
      conducted to analyse the asymmetries of DCL and EMG for the left and right leg.
      When the dynamic tilt surface increased, DCL scores significantly decreased
      (except forward, forward-rightward, and backward-leftward direction) and only RF
      muscle indicated significant differences. Left-right asymmetry was found in BF
      and MG muscles. No significant gender difference was observed in DCL and EMG.
      These data demonstrated that increased dynamic tilt surface may increase the
      displacement of center of pressure of certain directions, and stimulate RF
      activity in dynamic stance among sedentary middle-aged adults. Further studies
      should be conducted to examine the dynamic stance and muscle activity of the
      lower limb in age-matched patient groups with balance abnormalities.

PMID- 27865479
TI  - Evaluation of knee functional calibration with and without the effect of soft
      tissue artefact.
AB  - Functional calibration methods were devised to improve repeatability and accuracy
      of the knee flexion-extension axis, which is used to define the medio-lateral
      axis of the femur coordinate system in gait analysis. Repeatability of functional
      calibration methods has been studied extensively in healthy individuals, but not
      accuracy in the absence of a benchmark knee axis. We captured bi-plane
      fluoroscopy data of the knee joint in 17 subjects with unilateral total knee
      arthroplasty during treadmill walking. The prosthesis provided a benchmark knee
      axis to evaluate the functional calibration methods. Stereo-photogrammetry data
      of thigh and shank marker clusters were captured simultaneously to investigate
      the effect of soft tissue artefact (STA). Three methods were tested, the Axis
      Transformation Technique (ATT) finds the best single fixed axis of rotation,
      2DofKnee finds the axis that minimises knee varus-valgus and trajAJC finds the
      axis perpendicular to the trajectory, in the transverse plane of the femur, of a
      point located on the longitudinal axis of the tibia. Using fluoroscopy data,
      functional axes formed an angle of less than 2 degrees  in the transverse plane
      with the benchmark axis. True internal-external range of movement was correlated
      with decreased accuracy for ATT, while varus-valgus range of movement was
      correlated with decreased accuracy for 2DofKnee and trajAJC. STA had negative
      impact on accuracy and variability. Using stereo-photogrammetry data, the
      accuracy of 2DofKnee was 1.7 degrees (SD: 5.1 degrees ), smaller than ATT 2.9
      degrees (SD: 5.1 degrees ) but not to trajAJC 1.7 degrees (SD: 5.2 degrees ). Our
      results confirm that of previous studies, which utilised the femur condylar axis
      as reference.

PMID- 27865481
TI  - The influence of tethering and gravity on the stability of compliant liquid-lined
      airways.
AB  - This study revolves around two simple questions: 1) how does pulmonary airway
      recruitment/de-recruitment (RecDer) depend on the tethering support provided by
      surrounding airways and alveoli, and 2) does airway angle of inclination (theta)
      influence airway stability? These two questions are critical to understanding the
      existence and prevention of atelectrauma, which may contribute to ventilator
      induced lung injury (VILI). To address these questions, we develop PDMS 2mm ID
      compliant tubes that mimic pulmonary airways. Airway obstruction is modeled using
      silicone oil, and recruitment occurs through insufflation with a constant flow of
      air at Q=0.25ml/s. Parenchymal tethering is modeled through the use of a pressure
      chamber through which we independently establish the external pressure (Pext).
      Repetitive RecDer oscillation is observed as a function of Pext and theta. We
      find that airway collapse significantly increases the rate of instability, and
      this rate correlates strongly with the dimensionless film thickness
      (epsilon=h/R), where h is the film thickness and R is the transumural pressure
      dependent vessel radius. Furthermore, the angle of orientation influences RecDer
      oscillation, with stability decreased when airflow is directed in the upward
      direction. These results may provide insight into protective mechanical
      ventilation processes that can reduce the existence or severity of VILI.

PMID- 27865480
TI  - Biofluids, cell mechanics and epigenetics: Flow-induced epigenetic mechanisms of
      endothelial gene expression.
AB  - Epigenetics is the regulation of gene expression (transcription) in response to
      changes in the cell environment through genomic modifications that largely
      involve the non-coding fraction of the human genome and that cannot be attributed
      to modification of the primary DNA sequence. Epigenetics is dominant in
      establishing cell fate and positioning during programmed embryonic development.
      However the same pathways are used by mature postnatal and adult mammalian cells
      during normal physiology and are implicated in disease mechanisms. Recent
      research demonstrates that blood flow and pressure are cell environments that can
      influence transcription via epigenetic pathways. The principal epigenetic
      pathways are chemical modification of cytosine residues of DNA (DNA methylation)
      and of the amino tails of histone proteins associated with DNA in nucleosomes.
      They also encompass the post-transcriptional degradation of mRNA transcripts by
      non-coding RNAs (ncRNA). In vascular endothelium, epigenetic pathways respond to
      temporal and spatial variations of flow and pressure, particularly hemodynamic
      disturbed blood flow, with important consequences for gene expression. The
      biofluid environment is linked by mechanotransduction and solute transport to
      cardiovascular cell phenotypes via signaling pathways and epigenetic regulation
      for which there is an adequate interdisciplinary infrastructure with robust tools
      and methods available. Epigenetic mechanisms may be less familiar than acute
      genomic signaling to Investigators at the interface of biofluids, biomechanics
      and cardiovascular biology. Here we introduce a biofluids / cellular biomechanics
      readership to the principal epigenetic pathways and provide a contextual overview
      of endothelial epigenetic plasticity in the regulation of flow-responsive
      transcription.

PMID- 27865484
TI  - A Possible Amphidromic Relation Between Spontaneous Coronary Artery Dissection
      and Takotsubo Syndrome.

PMID- 27865482
TI  - Predictors of Suboptimal Gain in Exercise Capacity After Cardiac Rehabilitation.
AB  - Cardiac rehabilitation (CR) improves exercise capacity (EC), but not all CR
      participants achieve such improvements. Our primary aim was to develop a tool to
      identify those with suboptimal improvement in EC after CR. We retrospectively
      analyzed 541 patients enrolled in a phase-II CR program after a cardiac event or
      intervention from 2003 to 2014. EC was assessed with the 6-minute walk test. We
      developed a multivariate linear regression model and corresponding nomogram to
      predict EC after CR. The predictors included in the final model were age, gender,
      baseline EC, primary referral diagnosis, body mass index, systolic blood pressure
      at rest, triglycerides, low-density lipoprotein cholesterol, lipid-lowering
      medication use, and an interaction term of low-density lipoprotein cholesterol
      with lipid-lowering therapy. The prediction model was internally validated using
      bootstrap methods, and a nomogram was created for ease of use. In conclusion,
      this tool helps to identify those patients with suboptimal improvement in EC who
      could be targeted for individualized interventions to increase their performance.

PMID- 27865483
TI  - Acute Aortic Dissection With Intussusception of the Partition Between the True
      and False Channels Leading to Near Total Aortic Occlusion (True Aortic Stenosis).
AB  - Described herein are 2 patients with fatal acute aortic dissection resulting in a
      circumferential intimal-medial tear causing the partition between the true and
      false channels to roll up and propagate forward as an intra-aortic
      intussusception (a receiving within).

PMID- 27865485
TI  - Comparison of the Effectiveness of Stress Echocardiography Versus Myocardial
      Perfusion Imaging in Patients Presenting to the Emergency Department With Low
      Risk Chest Pain.
AB  - The aim of this study was to compare clinically relevant cardiovascular outcomes
      and downstream resource utilization associated with stress echocardiography (SE)
      and myocardial perfusion imaging (MPI) in emergency department patients with low
      risk chest pain. This was a retrospective analysis of health insurance claims
      data for a national sample of privately insured patients over the period January
      1 to December 31, 2011. Subjects were selected who presented to the emergency
      department with a primary or secondary diagnosis of chest pain and underwent
      either SE or MPI. The primary end points were the percentage of patients in each
      group who underwent downstream cardiac catheterization, revascularization, repeat
      noninvasive testing, return emergency department visit with chest pain, and
      hospitalization for myocardial infarction. The mean length of follow-up was 190
      days in both groups. Overall, 48,202 patients or 24,101 propensity-matched pairs
      were included in the final analysis. Compared with SE, MPI was associated with
      significantly higher odds of subsequent cardiac catheterization (adjusted odds
      ratio [AOR] 2.15; 95% confidence interval [CI] 1.99 to 2.33) and
      revascularization procedures (AOR 1.58; 95% CI 1.36 to 1.85) and repeat emergency
      department visits (AOR 1.14; 95% CI 1.11 to 1.19). The odds of repeat testing and
      myocardial infarction did not differ between groups. The average cost of
      downstream care was significantly higher in the MPI group ($2,193.80 vs
      $1,631.10, p <0.0001). According to the a priori rules specified for this
      comparative analysis, SE is more effective than MPI for privately insured
      patients who present to the emergency department with chest pain. In conclusion,
      these findings demonstrate the importance of assessing diagnostic tests based on
      how they affect hard end points because identification of disease, in and of
      itself, may not confer any clinical advantage.

PMID- 27865486
TI  - National single-step genomic method that integrates multi-national genomic
      information.
AB  - The aim of this paper was to develop a national single-step genomic BLUP that
      integrates multi-national genomic estimated breeding values (EBV) and associated
      reliabilities without double counting dependent data contributions from the
      different evaluations. Simultaneous use of all data, including phenotypes,
      pedigree, and genotypes, is a condition to obtain unbiased EBV. However, this
      condition is not always fully met, mainly due to unavailability of foreign raw
      data for imported animals. In dairy cattle genetic evaluations, this issue is
      traditionally tackled through the multiple across-country evaluation (MACE) of
      sires, performed by Interbull Centre (Uppsala, Sweden). Multiple across-country
      evaluation regresses all the available national information onto a joint pedigree
      to obtain country-specific rankings of all sires without sharing the raw data. In
      the context of genomic selection, the issue is handled by exchanging sire
      genotypes and by using MACE information (i.e., MACE EBV and reliabilities), as a
      valuable source of "phenotypic" data. Although all the available data are
      considered, these "multi-national" genomic evaluations use multi-step methods
      assuming independence of various sources of information, which is not met in all
      situations. We developed a method that handles this by single-step genomic
      evaluation that jointly (1) uses national phenotypic, genomic, and pedigree data;
      (2) uses multi-national genomic information; and (3) avoids double counting
      dependent data contributions from an animal's own records and relatives' records.
      The method was demonstrated by integrating multi-national genomic EBV and
      reliabilities of Brown Swiss sires, included in the InterGenomics consortium at
      Interbull Centre, into the national evaluation in Slovenia. The results showed
      that the method could (1) increase reliability of a national (genomic)
      evaluation; (2) provide consistent ranking of all animals: bulls, cows, and young
      animals; and (3) increase the size of a genomic training population. These
      features provide more efficient and transparent selection throughout a breeding
      program.

PMID- 27865487
TI  - Prediction and validation of residual feed intake and dry matter intake in Danish
      lactating dairy cows using mid-infrared spectroscopy of milk.
AB  - The present study explored the effectiveness of Fourier transform mid-infrared
      (FT-IR) spectral profiles as a predictor for dry matter intake (DMI) and residual
      feed intake (RFI). The partial least squares regression method was used to
      develop the prediction models. The models were validated using different external
      test sets, one randomly leaving out 20% of the records (validation A), the second
      randomly leaving out 20% of cows (validation B), and a third (for DMI prediction
      models) randomly leaving out one cow (validation C). The data included 1,044
      records from 140 cows; 97 were Danish Holstein and 43 Danish Jersey. Results
      showed better accuracies for validation A compared with other validation methods.
      Milk yield (MY) contributed largely to DMI prediction; MY explained 59% of the
      variation and the validated model error root mean square error of prediction
      (RMSEP) was 2.24kg. The model was improved by adding live weight (LW) as an
      additional predictor trait, where the accuracy R2 increased from 0.59 to 0.72 and
      error RMSEP decreased from 2.24 to 1.83kg. When only the milk FT-IR spectral
      profile was used in DMI prediction, a lower prediction ability was obtained, with
      R2=0.30 and RMSEP=2.91kg. However, once the spectral information was added, along
      with MY and LW as predictors, model accuracy improved and R2 increased to 0.81
      and RMSEP decreased to 1.49kg. Prediction accuracies of RFI changed throughout
      lactation. The RFI prediction model for the early-lactation stage was better
      compared with across lactation or mid- and late-lactation stages, with R2=0.46
      and RMSEP=1.70. The most important spectral wavenumbers that contributed to DMI
      and RFI prediction models included fat, protein, and lactose peaks. Comparable
      prediction results were obtained when using infrared-predicted fat, protein, and
      lactose instead of full spectra, indicating that FT-IR spectral data do not add
      significant new information to improve DMI and RFI prediction models. Therefore,
      in practice, if full FT-IR spectral data are not stored, it is possible to
      achieve similar DMI or RFI prediction results based on standard milk control
      data. For DMI, the milk fat region was responsible for the major variation in
      milk spectra; for RFI, the major variation in milk spectra was within the milk
      protein region.

PMID- 27865488
TI  - The influence of 3 different navel dips on calf health, growth performance, and
      umbilical infection assessed by clinical and ultrasonographic examination.
AB  - The objectives were to investigate the effect of 3 navel dips on (1) umbilical
      infection, (2) health events (pneumonia, diarrhea, and arthritis), and (3)
      average daily gain (ADG) in newborn dairy calves. A secondary aim was to compare
      the agreement of standardized ultrasonographic examination with clinical
      examination for the diagnosis of umbilical infection. In a randomized block
      design, newborn calves were assigned by birth order to 3 treatment groups: Navel
      Guard (NG; SCG-Solutions Inc., McDonough, GA), 7% iodine tincture (SI), and 2%
      chlorhexidine gluconate (CH). Treatment consisted of a single dip administration
      of the umbilicus immediately after removal of the newborn from the calving pen
      with 1 of the 3 navel dips. Weekly clinical examinations were carried out during
      the first 4wk of life with special attention being paid to the umbilicus, joints,
      respiratory tract, and fecal consistency, and included ultrasonographic
      evaluation of the umbilical structures. Body weight was assessed by using a girth
      tape at first and last evaluation. Multivariable logistic regression demonstrated
      no statistical differences in umbilical infection or health events. Multivariable
      linear regression analysis showed statistical differences in ADG (least squares
      means +/- standard errors) between groups, with 494+/-29, 571+/-29, and 516+/
      29g/d in groups NG, SI, and CH, respectively. Overall mortality during the study
      period was 9.5% (n=40). Postmortem examination identified diarrhea (80%) as the
      main disorder with 19, 4, and 9 calves in groups NG, SI, and CH, respectively.
      Kappa values yielded fair [0.30 (95% CI: -0.03-0.63)], good [0.61 (95% CI 0.46
      0.75)], moderate [0.53 (95% CI 0.31-0.74)], and moderate [0.49 (95% CI 0.19
      0.79)] agreement for detection of omphalitis between clinical and
      ultrasonographic evaluation in wk 1, 2, 3, and 4, respectively. Agreement was
      very good for detection of omphaloplebitis, with kappa values (95% CI) of 0.91
      (0.80-1.00), 0.87 (0.75-0.98), and 0.90 (0.76-1.00) in wk 2, 3, and 4,
      respectively, when omphalophlebitis was diagnosed. We detected no difference in
      the effectiveness of the 3 treatments in the prevention of umbilical infection,
      pneumonia, diarrhea, or arthritis.

PMID- 27865489
TI  - Effects of heating on the secondary structure of proteins in milk powders using
      mid-infrared spectroscopy.
AB  - Milk powder is an important source of protein for adults and children. Protein is
      very sensitive to heat, which may influence people's usage of nutrients in milk
      powder. In this study, we describe the temperature-induced secondary structure of
      protein in milk powders. In this study, whole milk powder containing 24% protein
      and infant formula containing 11% protein were heated from 25 to 100 degrees C.
      Attenuated total reflectance (ATR) spectra in the mid-infrared range 400-4,000cm
      1 were used to evaluate the heat effect on the secondary structure of protein in
      these 2 milk powders. The spectral changes as a function of temperature were
      maintained by difference spectra, second-derivative spectra and Gauss curve
      fitted spectra. The secondary structures of protein in the whole milk powder
      began to change at 70 degrees C and in the infant formula at 50 degrees C. The
      beta-sheet and beta-turn structures in the whole milk powder both decreased in
      the range of 70 to 85 degrees C, whereas alpha-helix structures increased. The
      loss of beta-sheet and beta-turn may contribute to the formation of alpha-helix
      in the whole milk powder. In infant formula powder, the beta-sheet structure
      showed a decrease and then increase, whereas the beta-turn structure showed an
      increase and then decrease in the range of 50 to 75 degrees C, and no change was
      found for alpha-helix structures. This implies that heating may induce the
      transformation from beta-sheet to beta-turn. Overall, whole milk powder had
      better temperature stability than infant formula powder, probably because of the
      lower content of lipid in the former than in the latter. These results help us
      understand the thermal stability of protein in milk powder.

PMID- 27865490
TI  - Effect of concentrate supplementation during the dry period on colostrum quality
      and effect of colostrum feeding regimen on passive transfer of immunity, calf
      health, and performance.
AB  - The objectives were to evaluate the effect of (1) supplementing concentrates to
      multiparous Holstein cows during the dry period on colostral and milk
      immunoglobulin G (IgG) concentration; and (2) feeding calves colostrum at either
      5 or 10% of their body weight (BW) on passive transfer of immunity, health, and
      performance. Holstein multiparous cows (n=37) were assigned to 1 of 2 nutritional
      treatments during an 8-wk dry period: (1) offered ad libitum grass silage only
      (GS) or (2) offered ad libitum access to the same grass silage plus concentrate
      [total mixed ration in a 75:25 dry matter (DM) ratio], providing a mean
      concentrate DM intake of 3.0kg/cow per day (GSC). Both treatment groups were
      offered identical levels of mineral and vitamin supplementation. Calves from
      these cows were weighed immediately after birth and fed either 5% (5BW) or 10%
      (10BW) of their BW in colostrum from their own dams within 2.5h of birth. Calves
      in the 10BW group received their second feed of colostrum from first-milking
      colostrum. Concentrate supplementation during the dry period had no effect on
      colostral IgG concentration, first-milking IgG yield, or fat, protein, and
      lactose contents. However, cows in GSC produced a greater mean milk yield over
      the first 8 milkings compared with cows in the GS group. Concentrate
      supplementation had no effect on calf BW or BW gain, serum IgG, or apparent
      efficiency of absorption (AEA) at 24h after birth. However, offspring from the
      GSC group had fewer cases of enteritis during the first 56d of life compared with
      offspring from the GS group. Calves in the 10BW group had greater mean serum IgG
      concentration for the first 3d following birth; however, at 24h after birth, we
      observed no treatment effect on AEA. The rate of enteritis was greater for calves
      in the 5BW treatment compared with 10BW. The colostrum-feeding regimen had no
      effect on BW gain or on the incidence of pneumonia among calf treatment groups.
      In conclusion, concentrate supplementation regimens offered during the dry period
      had a positive effect on colostrum yield, and offspring from the GSC group had a
      reduced rate of enteritis. Feeding 10% of BW of colostrum versus 5% of BW
      resulted in a greater serum IgG concentration for the first 3d postpartum, and
      10BW calves had a reduced rate of enteritis. Overall, to achieve successful
      passive transfer, decrease the rate of enteritis, and increase efficiency in the
      dairy calf, we recommend that dairy calves be fed 10% of their BW in colostrum as
      soon as possible after birth.

PMID- 27865491
TI  - Prevalence and risk factors for extended-spectrum beta-lactamase or AmpC
      producing Escherichia coli in organic dairy herds in the Netherlands.
AB  - Extended-spectrum beta-lactamase and AmpC-producing Escherichia coli (ESBL/AmpC)
      are an emerging problem and are hypothesized to be associated with antimicrobial
      use (AMU), and more specifically with the use of third- and fourth-generation
      cephalosporins. Whether ESBL/AmpC also occur in organic dairy herds, which have
      restricted AMU, is not known. Additionally, it is unknown whether, in addition to
      restricted AMU, other factors in organic herd management are associated with
      ESBL/AmpC herd status. The aim of this study was to estimate the prevalence of
      ESBL/AmpC in organic dairy herds in the Netherlands. Subsequently, the
      relationships between the ESBL/AmpC herd status and AMU and between ESBL/AmpC
      herd status and farmers' management were assessed in organic dairy herds. For
      this study, 90 randomly selected, officially registered organic dairy herds were
      included. The ESBL/AmpC herd status was determined based on the bacteriological
      culture result of a slurry sample. The sensitivity of testing slurry samples for
      ESBL/AmpC herd status is less than 100% for detecting herds with a low ESBL/AmpC
      prevalence. For that reason, herds that tested positive for ESBL/AmpC in slurry
      were defined as positive and herds with negative slurry samples were defined as
      unsuspected. A comprehensive questionnaire on management practices was conducted
      and records on specified antimicrobials that were provided to these herds by the
      veterinary service providers were obtained. From the data on antimicrobial
      supplies by the veterinarian, the animal daily defined dose of antimicrobials per
      farm per year (DDDAF) was calculated. Descriptive statistics were used to
      describe the relation between the ESBL/AmpC herd status and DDDAF. Multivariable
      logistic regression models were used to evaluate management factors associated
      with the ESBL/AmpC herd status. We found ESBL/AmpC in 12 of the 90 (13%; 95%
      confidence interval=7-22%) slurry samples from organic dairy herds. The median
      DDDAF in organic dairy herds was 0.5, which was not significantly different
      between ESBL/AmpC-positive and unsuspected dairy herds. No association could be
      found between the use of different types of antimicrobials, such as third- and
      fourth-generation cephalosporins, and ESBL/AmpC herd status. Factors that were
      associated with higher odds of being ESBL/AmpC-positive were pig farms located
      within a 2-km radius of the barn, applying parental treatment for clinical
      mastitis, and providing milk replacer to the female calves after colostrum
      intake. The prevalence of ESBL/AmpC in organic dairy herds appeared lower than
      the prevalence in previous studies conducted in conventional dairy herds.
      Apparently, ESBL/AmpC are also present in herds with low AMU; this indicates that
      other factors than AMU are also associated with ESBL/AmpC herd status.

PMID- 27865492
TI  - Peripheral blood mononuclear cell proliferation and cytokine production in sheep
      as affected by cortisol level and duration of stress.
AB  - A large number of studies recognize glucocorticoids (Gc) as suppressors of
      inflammation; Gc exert an important role in coordinating the magnitude and
      duration of host immune responses. In the present in vitro investigation, we
      tested incremental levels of cortisol to verify the immunosuppressive or
      immunopermissive role of cortisol in sheep peripheral blood mononuclear cells
      (PBMC) after acute and chronic stress. Phytohemagglutinin (PHA)-stimulated PBMC
      were cultured for 24h and 96h at 37 degrees C with 5% of CO2 and varying cortisol
      levels: 10 ng/mL (baseline), 100 ng/mL (physiological poststressor), and 1,000
      ng/mL [hyperactivated hypothalamic-pituitary-adrenal (HPA) axis]. The cell-free
      supernatants were collected for determination of IL-6, IL-1beta, and IL-10 by
      ELISA, and the bromodeoxyuridine assay was performed on cells. Physiological
      cortisol concentration negatively affected the levels of IL-6 secreted by PBMC,
      resulting in increased cell proliferation after acute stress (24h of incubation).
      However, physiological cortisol concentration exhibited a reduction in cell
      proliferation induced by increased levels of IL-6 secreted by PBMC during chronic
      stress (96h of incubation). The cortisol concentration representing a
      hyperactivated HPA axis led to a reduction in cell proliferation after acute
      stress, which was probably induced by the elevated IL-10 production. Our results
      demonstrate that in sheep the effect of Gc on the immune system was related to
      the magnitude and the duration of stress. In particular, cortisol levels higher
      than physiological concentrations suppressed cell proliferation soon after acute
      stress. Instead, the physiological poststressor concentration of cortisol
      affected the immune responses in a bidirectional manner depending on the duration
      of the stressor.

PMID- 27865493
TI  - Genetic and genomic analysis of hyperthelia in Brown Swiss cattle.
AB  - Supernumerary teats (SNT) are any abnormal teats found on a calf in addition to
      the usual and functional 4 teats. The presence of SNT has also been termed
      "hyperthelia" since the end of the 19th century. Supernumerary teats can act as
      an incubator for bacteria, infecting the whole udder, and can interfere with the
      positioning of the milking machine, and consequently, have economic relevance.
      Different types of SNT are observed at different positions on the udder. Caudal
      teats are in the rear, ramal teats are attached to another teat, and intercalary
      teats are found between 2 regular teats. Not all teats are equally developed;
      some are completely functional but most are rudimentary and not attached to any
      mammary gland tissue. Recently, different studies showed the poly/oligogenic
      character of these malformations in cattle as well as in other mammalian species.
      The objective of this study was to analyze the genetic architecture and incidence
      of hyperthelia in Swiss Brown Swiss cattle using both traditional genetic
      evaluation as well as imputed whole genome sequence variant information. First,
      phenotypes collected over the last 20 yr were used together with pedigree
      information for estimation of genetic variance. Second, breeding values of Brown
      Swiss bulls were estimated applying the BLUP algorithm. The BLUP-EBV were
      deregressed and used as phenotypes in genome-wide association studies. The gene
      LGR5 on chromosome 5 was identified as a candidate for the presence of SNT. Using
      alternative trait coding, genomic regions on chromosome 17 and 20 were also
      identified as being involved in the development of SNT with their own
      supernumerary mammary gland tissue. Implementing knowledge gained in this study
      as a routine application allows a more accurate evaluation of the trait and
      reduction of SNT prevalence in the Swiss Brown Swiss cattle population.

PMID- 27865494
TI  - Changes in terpenoid composition of milk and cheese from commercial sheep flocks
      associated with seasonal feeding regimens throughout lactation.
AB  - Changes in the terpenoid content of milk and cheese from commercial sheep flocks
      monitored throughout lactation in the Cantabrian area of northern Spain were
      investigated. The flocks followed the same seasonal feeding strategy during
      lactation: indoor feeding in winter (early lactation) based on concentrate and
      forage; part-time grazing in the valley in early spring (mid lactation); and from
      mid spring on (late lactation), flocks were managed under extensive mountain
      grazing. In the present study design, seasonal feeding and lactation stage were
      intrinsically linked and could not be considered in isolation, and a holistic
      approach was necessary to consider the whole production management of the
      commercial flocks studied. Furthermore, the study focused on the identification
      of sesquiterpenoid ratios to differentiate milks and cheeses produced under
      extensive mountain grazing from those produced under other seasonal feeding
      regimens. Total abundance of mono- and sesquiterpenoids and that of individual
      compounds such as alpha-pinene, beta-caryophyllene, alpha-humulene, alpha
      amorphene, and gamma-cadinene significantly increased in milk and cheese from
      indoor feeding to mountain extensive grazing. Sesquiterpenoid ratios such as
      gamma-cadinene/alpha-muurolene, gamma-cadinene/delta-cadinene, beta
      caryophyllene/alpha-muurolene, and (beta-caryophyllene + gamma-cadinene)/alpha
      muurolene were used to differentiate mountain milks and cheeses from those from
      indoor feeding and part-time grazing in the valley. Multivariate discriminant
      analysis applied to individual terpenoids and sesquiterpenoid ratios showed milk
      and cheese samples classified into 2 groups: samples from indoor feeding and part
      time grazing in the valley were classified together, and clearly separated from
      mountain milks and cheeses. The results of the present study showed that the
      sesquiterpenoid ratios approach could help to differentiate mountain dairy
      products from others obtained under other specific feeding regimens in a local
      environment.

PMID- 27865495
TI  - Assessment of multifunctional activity of bioactive peptides derived from
      fermented milk by specific Lactobacillus plantarum strains.
AB  - Milk-derived bioactive peptides with a single activity (e.g., antioxidant,
      immunomodulatory, or antimicrobial) have been previously well documented;
      however, few studies describe multifunctional bioactive peptides, which may be
      preferred over single-activity peptides, as they can simultaneously trigger,
      modulate, or inhibit multiple physiological pathways. Hence, the aim of this
      study was to assess the anti-inflammatory, antihemolytic, antioxidant,
      antimutagenic, and antimicrobial activities of crude extracts (CE) and peptide
      fractions (<3 and 3-10 kDa) obtained from fermented milks with specific
      Lactobacillus plantarum strains. Overall, CE showed higher activity than both
      peptide fractions (<3 and 3-10 kDa) in most of the activities assessed.
      Furthermore, activity of <3 kDa was generally higher, or at least equal, to the 3
      to 10 kDa peptide fractions. In particular, L. plantarum 55 crude extract or
      their fractions showed the higher anti-inflammatory (723.68-1,759.43MUg/mL of
      diclofenac sodium equivalents), antihemolytic (36.65-74.45% of inhibition), and
      antioxidant activity [282.8-362.3umol of Trolox (Sigma-Aldrich, St. Louis, MO)
      equivalents]. These results provide valuable evidence of multifunctional role of
      peptides derived of fermented milk by the action of specific L. plantarum
      strains. Thus, they may be considered for the development of biotechnological
      products to be used to reduce the risk of disease or to enhance a certain
      physiological function.

PMID- 27865496
TI  - Peroxisome proliferator-activated receptor delta facilitates lipid secretion and
      catabolism of fatty acids in dairy goat mammary epithelial cells.
AB  - In rodents, peroxisome proliferator-activated receptor delta (PPARD) is
      associated primarily with catabolism of fatty acids. However, the role of PPARD
      in regulating lipid metabolism in ruminant mammary gland remains unknown. In the
      present study, we assessed the mRNA abundance of PPARD at 3 stages of lactation
      in goat mammary tissue. Results revealed that PPARD had lower expression at peak
      lactation than in the nonlactating period. Luciferase assays revealed that GW0742
      (GW), a specific PPARD ligand, enhanced the activity of the PPARD response
      element in goat mammary epithelial cells. Activation of PPARD by GW selectively
      upregulated the expression of genes related to fatty acid activation (ACSL1),
      lipid droplet formation (PLIN2), and transport (FABP4), and had no effect on
      genes involved in de novo fatty acid synthesis (ACACA and FASN), desaturation
      (SCD), hydrolysis and oxidation (PNPLA2 and CPT1A), transport and uptake (FABP3
      and CD36), or triacylglycerol synthesis (DGAT1 and AGPAT6) in goat mammary
      epithelial cells. In contrast, knockdown of PPARD using small interfering RNA
      dramatically decreased the expression of genes related to fatty acid activation
      (ACSL1) and lipid formation (PLIN2) and increased the expression of genes related
      to fatty acid transport (FABP3) and triacylglycerol synthesis (AGPAT6 and DGAT1).
      The expression of genes related to fatty acid synthesis (FASN), hydrolysis
      (PNPLA2), and fatty acid oxidation (CPT1A) was downregulated significantly only
      after knockdown of PPARD in cells incubated with GW. We observed no significant
      change in fatty acid profiles. However, the total cellular triacylglycerol
      increased after knockdown of PPARD in goat mammary epithelial cells plus GW.
      Collectively, these results highlight an important role for PPARD in the
      homeostasis of ruminant mammary cells by facilitating fatty acid activation and
      lipid droplet formation and secretion.

PMID- 27865497
TI  - Invited review: Abomasal emptying in calves and its potential influence on
      gastrointestinal disease.
AB  - Creating the ideal nutrition program for calves is a demanding task that has
      undergone tremendous change in recent years. Products and technologies including
      novel milk replacers and automated calf feeding systems have been developed to
      facilitate the ability of dairy producers to feed for higher growth rates before
      weaning. The creation of new feeding programs and milk replacers has to be looked
      at carefully, not only from a nutrition point of view but also from the
      perspective of a potential effect on physiologic digestion and calf health.
      Abomasal emptying is a critical factor that may link nutrition and disease. The
      purpose of this article is to review both intrinsic and extrinsic factors that
      are responsible for abomasal emptying. Predominant extrinsic factors controlling
      abomasal emptying include meal volume, energy density, and osmolality along with
      the content and source of protein. This article also reviews experimental methods
      used to measure abomasal emptying in the calf including those that would be
      appropriate for use under field conditions. Among these methods, the use of
      ultrasonography and different absorption tests (d-xylose, acetaminophen) as tools
      to measure abomasal emptying are discussed. The relationship between abomasal
      emptying and disease is explored, particularly as it relates to abomasal bloat.
      Abomasal bloat is a complex syndrome that seems to be increasing in frequency and
      whose etiology likely at least partially involves slowing of abomasal emptying.
      Suggestions for minimizing the effect of feeding programs on abomasal emptying
      are explored as well as needs for future research.

PMID- 27865499
TI  - Optimally achieving milk bulk tank somatic cell count thresholds.
AB  - High somatic cell count in milk leads to reduced shelf life in fluid milk and
      lower processed yields in manufactured dairy products. As a result, farmers are
      often penalized for high bulk tank somatic cell count or paid a premium for low
      bulk tank somatic cell count. Many countries also require all milk from a farm to
      be lower than a specified regulated somatic cell count. Thus, farms often cull
      cows that have high somatic cell count to meet somatic cell count thresholds.
      Rather than naively cull the highest somatic cell count cows, a mathematical
      programming model was developed that determines the cows to be culled from the
      herd by maximizing the net present value of the herd, subject to meeting any
      specified bulk tank somatic cell count level. The model was applied to test-day
      cows on 2 New York State dairy farms. Results showed that the net present value
      of the herd was increased by using the model to meet the somatic cell count
      restriction compared with naively culling the highest somatic cell count cows.
      Implementation of the model would be straightforward in dairy management decision
      software.

PMID- 27865498
TI  - The effects of periparturient administration of flunixin meglumine on the health
      and production of dairy cattle.
AB  - Research on the assessment and management of pain in cows following difficult or
      assisted calving is still limited, especially on the effects of analgesics
      intended to mitigate this pain. The purpose of this study was to assess the
      effects of flunixin meglumine on the health and production of Holstein cows after
      calving. In total, 34 flunixin-treated and 38 placebo-treated animals were
      enrolled in a precalving treatment trial. A total of 633 animals given flunixin
      and 632 animals administered a placebo were enrolled in a postcalving treatment
      trial. In both cases, animals were randomly assigned to treatment, and
      researchers were blind to treatment condition until after analysis. A total of
      1,265 animal records were analyzed for milk production for the first 14d in milk
      and health outcomes for the first 30d in milk. Animals treated with flunixin
      meglumine before calving had a significantly increased risk of stillbirth.
      Animals treated immediately after calving had increased odds of having a retained
      placenta and, in turn, increased risk of a high temperature, decreased milk
      production, and an increased risk of developing metritis. The administration of
      flunixin meglumine within 24h of parturition is not recommended in dairy cattle.

PMID- 27865500
TI  - Lipopolysaccharide derived from the digestive tract provokes oxidative stress in
      the liver of dairy cows fed a high-grain diet.
AB  - The aims of this study were to measure oxidative stress parameters and to
      investigate the molecular mechanism triggered by grain-induced subacute ruminal
      acidosis in mid-lactation cows. Twelve Holstein-Friesian cows with an average
      weight of 455+/-28kg were divided into 2 groups and subjected to 2 diets over
      18wk: either a low-grain (forage-to-concentrate ratio=6:4) or a high-grain
      (forage-to-concentrate ratio=4:6) diet based on dry matter. Being fed a long-term
      high-grain diet resulted in a significant decrease in rumen pH and a significant
      increase in ruminal lipopolysaccharide (LPS) at 4 h postfeeding in the morning.
      The increase was also observed in LPS concentrations in the portal vein, hepatic
      vein, and jugular vein blood plasma as well as reduced milk yield in a high-grain
      diet. Cows fed a high-grain diet had lower levels of catalase and glutathione
      peroxidase (GPx) activity and total antioxidant capacity than cows fed a low
      grain diet; however, super oxide dismutase (SOD) activity and malondialdehyde
      (MDA) levels were higher in both the liver and the plasma of high-grain than in
      low-grain cows. Positive correlations were observed between plasma LPS versus
      hepatic MDA, plasma MDA, and hepatic SOD activity, whereas hepatic GPx and plasma
      GPx were negatively correlated with plasma LPS. The relative mRNA abundances of
      GPX1 and CAT were significantly lower in the liver of cows fed a high-grain diet
      than those fed a low-grain diet, whereas SOD1 was significantly higher in cows
      fed a high-grain diet than cows fed a low-grain diet. The expression levels of
      Nrf2, NQO1, MT1E, UGT1A1, MGST3, and MT1A were downregulated, whereas NF-kB was
      upregulated, in cows fed a high-grain diet. Furthermore, nuclear factor E2
      related factor 2 (Nrf2) total protein and mRNA levels were significantly lower
      than in low-grains. Our results demonstrate the relationship between the
      translocated LPS and the suppression of cellular antioxidant defense capacity,
      which lead to increased oxidative stress and suggests that the Nrf2-dependent
      antioxidant response may be affected by higher levels of LPS translocated to the
      bloodstream.

PMID- 27865501
TI  - Cytological endometritis at artificial insemination in dairy cows: Prevalence and
      effect on pregnancy outcome.
AB  - The aims of our field study in dairy cows were (1) to consolidate cytotape (CT)
      as a valid technique to diagnose cytological endometritis (CYTO) during
      artificial insemination (AI); (2) to establish a cutoff point concerning the
      polymorphonuclear cells (PMN) proportion to diagnose CYTO at AI; (3) to assess
      the prevalence of CYTO at AI; and (4) to evaluate the effect of CYTO on the
      pregnancy outcome of that AI. The investigation was performed using 1,625 AI-CT
      samples harvested from 873 Holstein-Friesian cows from 18 dairy farms in the
      Flemish region of Belgium. The CT device consisted of adapting a 1.5-cm piece of
      paper tape on the top of a conventional AI catheter covered with a double guard
      sheet, allowing an endometrial cytology sample to be taken when performing an AI.
      A receiving operator characteristic curve was built to assess the threshold level
      above which the PMN proportion significantly affected the AI success. Multilevel
      generalized mixed-effect models were built to identify factors affecting the
      pregnancy outcome of the AI under investigation. Only 7 samples (0.4%) harvested
      in 5 cows were discarded because of low-quality parameters. The cutoff point for
      CYTO at AI was set at >=1% PMN (sensitivity=33.8%, specificity=88.6%). Prevalence
      of CYTO at AI was 27.8%. The conception rate for CYTO-positive samples was 32.7%,
      whereas it was 47% for CYTO-negative samples. A CYTO-negative AI had 1.8 [odds
      ratio (OR)] more chances to become pregnant than a CYTO-positive one. Other
      factors identified as detrimental for the pregnancy outcome were body condition
      score <=1.5 (OR=0.6), relative 305-d milk yield (OR=0.9), dystocia (OR=0.3),
      parity >=2 (OR=0.7), and warm months of the year. In conclusion, CT is a
      consolidated technique to diagnose CYTO at AI, PMN 1% is the threshold level to
      diagnose CYTO at AI, around one-quarter of inseminated uteri suffer from CYTO,
      and affected uteri having a significantly lower chance to become pregnant from
      that insemination.

PMID- 27865503
TI  - Effect of claw disorders on milk production, fertility, and longevity, and their
      economic impact in Spanish Holstein cows.
AB  - The aims of this study were (1) to estimate the phenotypic association between
      different degrees of severity of claw disorders and production, fertility
      performance, and longevity in Spanish dairy cattle, and (2) to quantify its
      economic impact at the animal and herd level. In this study, claw data comprised
      108,468 trimmings collected between 2012 and 2014 by 25 trimmers from 804
      Holstein dairy herds. The claw disorders considered were the 3 most frequent
      disorders in Spanish dairy herds: dermatitis (DE), sole ulcer (SU), and white
      line disease (WL). The presence of SU or WL was associated with a significant
      decrease in milk production and was more important in cows in second or later
      lactations. A severe lesion of SU or WL lead to twice the milk losses associated
      with a mild lesion, ranging from 1.47 to 2.66kg/d of energy-corrected milk. The
      presence of SU or WL during the early lactation period was associated with more
      days open, fewer inseminations to get pregnant, and longer calving to first
      service interval (4.83 and 8.0 d longer due to mild and severe lesions of SU,
      respectively, and 4.94 and 17.43 d longer due to mild and severe lesions of WL,
      respectively). The occurrence of a case of SU or WL in first lactation had a
      significant effect on longevity, with severe lesions reducing up to 71 d of
      productive life. The cost of a mild lesion ranged from $53 to $232 per affected
      cow and year, whereas the cost of a severe lesion ranged from $402 to $622 per
      affected cow and year. The annual costs per cow for DE, SU, and WL were $10.80,
      $50.9, and $43.2, respectively. An average herd with 64 cows had an extra
      expenditure of $691/yr due to DE, $3,256/yr due to SU, and $2,765/year due to WL.
      Milk losses, longer calving intervals, and premature culling contributed to more
      than half of the costs. Therefore, providing this information to farmers could
      help decide on strategies to reduce the incidence of claw disorders on the farm.

PMID- 27865502
TI  - Retail lighting and packaging influence consumer acceptance of fluid milk.
AB  - Little is known about the effect of retail light-emitting diode (LED) exposure on
      consumer acceptance of milk. The study objective was to determine effects of
      fluorescent and LED lighting under retail storage conditions on consumer
      acceptance of milk. Consumer acceptance of milk stored under retail conditions
      was determined through sensory evaluation (2 studies; n=150+ each) and analytical
      measures (dissolved oxygen, secondary oxidation products, riboflavin retention).
      Study 1 evaluated milk stored in high-density polyethylene (HDPE) packages for 4h
      under LED light (960 lx). Commercially available HDPE package treatments included
      translucent HDPE (most commonly used), white HDPE [low concentration (1.3%)
      TiO2], and yellow HDPE; in addition, HDPE with a higher TiO2 concentration (high
      white; 4.9% TiO2) and a foil-wrapped translucent HDPE (control) were tested.
      Translucent and control packages also were tested under fluorescent light. Study
      2 evaluated polyethylene terephthalate (PET) packages for 4h under fluorescent
      and LED light (1,460 lx). The PET packaging included 2 treatments (medium, 4.0%
      TiO2; high, 6.6% TiO2) as well as translucent HDPE (exposed to fluorescent),
      clear PET (fluorescent and LED), and light-protected control. Overall mean
      acceptability of milk ranged from "like slightly" to "like moderately" with
      significantly lower acceptability for milk exposed to fluorescent light. Milk in
      HDPE and PET packages had comparable overall acceptability scores when exposed to
      LED light. Only the fluorescent light condition (both PET and HDPE) diminished
      overall acceptability. Fluorescent light exposure negatively influenced flavor
      with significant penalty (2.0-2.5 integers) to overall acceptability of milk in
      translucent HDPE and clear PET. The LED also diminished aftertaste of milk
      packaged in translucent HDPE. Changes in dissolved oxygen content, as an
      indication of oxidation, supported the observed differences in consumer
      acceptance of milk stored under fluorescent and LED light. Consumers like the
      flavor of fresh milk, which can be protected by selecting appropriate packaging
      that blocks detrimental light wavelengths.

PMID- 27865504
TI  - Validation of a fast real-time PCR method to detect fraud and mislabeling in milk
      and dairy products.
AB  - Fast real-time PCR TaqMan assays were developed and validated for species
      identification in dairy products. Based on the amplification of 12S rRNA and cytB
      partial genes of mitochondrial DNA, the methods were demonstrated to be
      sensitive, fast, and species-specific for Bos taurus, Ovis aries, Bubalus
      bubalis, and Capra hircus. The limit of detection calculated was lower than 1%,
      and the efficiency was reported to be higher than 96% in every assay. An internal
      amplification control was used to detect possible false negatives. The method was
      validated by means of laboratory-prepared samples mixing different species.
      Moreover, 18 commercial dairy samples were analyzed by both real-time PCR and
      isoelectric focusing, the official European Union reference method. The 4 TaqMan
      assays were confirmed to be a useful tool for milk and dairy product
      authentication.

PMID- 27865505
TI  - Nitrogen utilization, preweaning nutrient digestibility, and growth effects of
      Holstein dairy calves fed 2 amounts of a moderately high protein or conventional
      milk replacer.
AB  - Studies have shown that calves fed milk replacers (MR) with crude protein (CP)
      concentrations greater than 20%, as typically found in conventional MR, have
      higher dry matter intakes (DMI) and greater average daily gains (ADG) but consume
      less starter, which can lead to stress during weaning and reduced rumen
      development. The greater amount of CP being fed to preweaned calves may alter
      their nitrogen (N) balance, and excess N may be excreted in the urine. The
      objective of this study was to determine N utilization in preweaned calves fed
      diets varying in the amount of CP and MR fed. This study used 24 newborn dairy
      heifer calves blocked by birth and randomly assigned to 1 of 3 treatments: (1)
      446g dry matter (DM) of a conventional MR (CON; 20% CP, 20% fat), (2) 669g DM of
      a moderately high protein MR (moderate; MOD; 26% CP, 18% fat), or (3) 892g DM of
      a moderately high protein MR (aggressive; AGG; 26% CP, 18% fat). All calves had
      ad libitum access to starter and water. Both MR and starter were medicated with
      decoquinate. During weaning (d 43-49), the morning MR feeding ceased. On d 50,
      all MR feedings ended; however, starter and water intakes were continuously
      recorded until d 56. At 5wk of age, urine was collected using urinary catheters
      for 3d and chromium oxide was administered by bolus at 2g/d for 7d to estimate N
      efficiency. Calves fed MOD and AGG had similar starter intakes, feed
      efficiencies, and ADG, with the combined treatments having reduced starter
      intakes (258 vs. 537g/d), greater ADG (674 vs. 422g/d), and improved feed
      efficiency (0.57 vs. 0.45 gain:feed) compared with CON calves preweaning.
      However, DMI and water intake were similar across all treatments. Results from
      the N utilization phase showed that MOD and AGG treatments had similar but lower
      N efficiency compared with CON calves (45.5 vs. 52.7%). This could be due to MOD-
      and AGG-fed calves having greater urine volume and thereby, greater combined
      urine N output compared with CON calves (17.6 vs. 12.1 g/d). In summary, feeding
      >0.66kg (DM) from a 26% CP MR increased ADG and improved feed efficiency during
      the preweaning period but reduced starter intake and lowered N efficiency.

PMID- 27865506
TI  - Synthesis of the suspected trans-11,cis-13 conjugated linoleic acid isomer in
      ruminant mammary tissue by FADS3-catalyzed Delta13-desaturation of vaccenic acid.
AB  - The octadecadienoic conjugated linoleic acid (CLA) isomer with trans-11 and cis
      13 double bonds (trans-11,cis-13 CLA) has been described in ruminant milk. For
      now, this specific CLA is suspected to derive exclusively from ruminal
      biohydrogenation of dietary alpha-linolenic acid. However, in rodents, the fatty
      acid desaturase 3 (FADS3) gene was recently shown to code for an enzyme able to
      catalyze the unexpected Delta13-desaturation of vaccenic acid, producing a
      Delta11,13-CLA with all the structural characteristics of the trans-11,cis-13
      isomer, although no commercial standard exists for complete conclusive
      identification. Because the FADS3 gene has already been reported in bovine
      animals, we hypothesized in the present study that an alternative direct FADS3
      catalyzed Delta13-desaturation of vaccenic acid in mammary tissue may therefore
      co-exist with alpha-linolenic acid biohydrogenation to explain the final ruminant
      milk trans-11,cis-13 CLA presence. Here, we first confirm that the FADS3 gene is
      present in ruminant mammal genomic sequence databases. Second, we demonstrate
      that the Delta11,13-CLA found in milk fat and the highly probable trans-11,cis-13
      CLA isomer produced by rodent FADS3 possess exactly the same structural
      characteristics. Then, we show that bovine mammary MAC-T and BME-UV epithelial
      cells express both FADS3 and stearoyl-CoA desaturase 1 (SCD1) mRNA and are able
      to synthesize both the suspected trans-11,cis-13 CLA and cis-9,trans-11CLA
      (rumenic acid) isomers when incubated with vaccenic acid. Finally, the
      concomitant presence of the suspected trans-11,cis-13 CLA isomer with FADS3 mRNA
      was shown in goat mammary tissue, whereas both were conversely very low or even
      absent in goat liver. Therefore, this study provides several lines of evidence
      that, by analogy with rumenic acid, trans-11,cis-13 CLA may originate both from
      ruminal biohydrogenation and from direct FADS3-catalyzed Delta13-desaturation of
      vaccenic acid in mammary tissue.

PMID- 27865507
TI  - Plasma protein and supplemental isoleucine in milk replacers for dairy calves.
AB  - We measured the effects of milk replacers containing 0, 33, 66, or 100% of the
      total replaceable whey protein as bovine plasma protein (PP), without or with Ile
      supplementation, on the intake, growth, and health of 124 male Holstein calves
      for 35d. Milk replacers were formulated to contain 18% crude protein and 20% fat,
      with contents of Lys and Met equalized. When fed to calves at 1.5% of body weight
      (dry matter basis) under thermoneutral conditions, diets were predicted to allow
      average daily gains of 0.55kg/d based on metabolizable energy or 0.40kg/d based
      on apparent digestible protein. Protein supply was more limiting than energy so
      that differences in protein use could be detected. Dry matter intakes decreased
      with increased PP, irrespective of Ile supplementation. Final body weights
      decreased linearly with increasing PP, regardless of Ile supplementation. Average
      daily gain tended to be affected in a quadratic manner as PP increased, either
      with or without Ile supplementation; average daily gain and gain-feed ratio were
      greatest for calves fed diets containing 33% PP and lowest for calves fed 100%
      PP. The analyzed Lys content in the milk replacers was variable compared with
      formulated values, and this may have affected growth results. However, the gain
      Lys ratio was affected by an interaction of the linear effect of increasing PP
      with Ile supplementation: it decreased with increasing PP but was improved by
      supplementation with Ile for calves fed 100% PP. Body measurements decreased with
      increasing PP inclusion; only decreased heart girth was reversed with Ile
      supplementation. The lowest and highest inclusion of PP, regardless of Ile
      supplementation, decreased the occurrence of scours compared with the control
      diet (all whey protein). Calves fed the lowest and highest PP without Ile
      supplementation also had fewer total days of scours in the first 21d. In
      addition, calves fed 100% PP without supplementation of Ile had fewer days of
      medication compared with the control diet. Even at the highest PP inclusion,
      average daily gain was minimally affected if Ile was supplemented. Growth rates,
      gain-feed ratio, and gain-Lys ratio were decreased at higher PP inclusion, but
      Ile overcame part of the reduction in gain-Lys ratio for 100% PP. Additional
      titration studies will have to be conducted to determine optimal PP inclusion
      rates, with a focus on supplementation of potentially limiting essential AA, as
      well as effects at higher growth rates.

PMID- 27865508
TI  - Occurrence of methicillin-resistant Staphylococcus aureus in dairy cattle herds,
      related swine farms, and humans in contact with herds.
AB  - In this study we investigated the circulation of methicillin-resistant
      Staphylococcus aureus (MRSA) in 2 dairy cattle farms (farm A and B), previously
      identified as MRSA-positive in bulk tank milk samples, and epidemiologically
      related to swine farms. Collected specimens included quarter milk samples and
      nasal swabs from dairy cows, pig nasal swabs collected at both the farm and
      slaughterhouse level, environmental dust samples, and human nasal swabs from the
      farms' owners and workers. The prevalence of MRSA was estimated at the herd level
      by testing quarter milk samples. The prevalence of MRSA was 4.8% (3/63; 95%
      confidence interval=0-10.2%) and 60% (33/55; 95% confidence interval=47.05-72.95)
      in farm A and B, respectively. In farm A, MRSA was also isolated from humans,
      pigs sampled at both farm and slaughterhouse level, and from environmental
      samples collected at the pig facilities. The dairy cattle facilities of farm A
      tested negative for MRSA. In farm B, MRSA was isolated from environmental dust
      samples in both the cattle and pig facilities, whereas nasal swabs collected from
      cows and from humans tested negative. Sixty-three selected MRSA isolates obtained
      from different sources in farm A and B were genetically characterized by
      multilocus sequence typing, spa-typing, ribosomal spacer-PCR, and also tested for
      the presence of specific virulence genes and for their phenotypical antimicrobial
      susceptibility by broth microdilution method. Different clonal complex (CC) and
      spa-types were identified, including CC398, CC97, and CC1, CC already reported in
      livestock animals in Italy. The MRSA isolates from quarter milk of farm A and B
      mostly belonged to CC97 and CC398, respectively. Both lineages were also
      identified in humans in farm A. The CC97 and CC398 quarter milk isolates were
      also identified as genotype GTBE and GTAF by ribosomal spacer-PCR respectively,
      belonging to distinct clusters with specific virulence and resistance patterns.
      The GTBE and GTAF clusters also included swine, environmental, and human isolates
      from both farms. A high heterogeneity in the genetic and phenotypic profiles was
      observed in environmental isolates, in particular from farm B. These results
      demonstrate the possibility of a dynamic sharing and exchange of MRSA lineages or
      genotypes between different species and farm compartments in mixed-species farms.
      The risk of transmission between swine and related dairy cattle herds should be
      considered. Our findings also confirm the zoonotic potential of livestock
      associated MRSA and underline the importance of applying biosecurity measures and
      good hygiene practices to prevent MRSA spread at the farm level and throughout
      the food production chain.

PMID- 27865509
TI  - Effect of incremental amounts of camelina oil on milk fatty acid composition in
      lactating cows fed diets based on a mixture of grass and red clover silage and
      concentrates containing camelina expeller.
AB  - Camelina is an ancient oilseed crop that produces an oil rich in cis-9,cis-12
      18:2 (linoleic acid, LA) and cis-9,cis-12,cis-15 18:3 (alpha-linolenic acid,
      ALA); however, reports on the use of camelina oil (CO) for ruminants are limited.
      The present study investigated the effects of incremental CO supplementation on
      animal performance, milk fatty acid (FA) composition, and milk sensory quality.
      Eight Finnish Ayrshire cows (91d in milk) were used in replicated 4*4 Latin
      squares with 21-d periods. Treatments comprised 4 concentrates (12kg/d on an air
      dry basis) based on cereals and camelina expeller containing 0 (control), 2, 4,
      or 6% CO on an air-dry basis. Cows were offered a mixture of grass and red clover
      silage (RCS; 1:1 on a dry matter basis) ad libitum. Incremental CO
      supplementation linearly decreased silage and total dry matter intake, and
      linearly increased LA, ALA, and total FA intake. Treatments had no effect on
      whole-tract apparent organic matter or fiber digestibility and did not have a
      major influence on rumen fermentation. Supplements of CO quadratically decreased
      daily milk and lactose yields and linearly decreased milk protein yield and milk
      taste panel score from 4.2 to 3.6 [on a scale of 1 (poor) to 5 (excellent)],
      without altering milk fat yield. Inclusion of CO linearly decreased the
      proportions of saturated FA synthesized de novo (4:0 to 16:0), without altering
      milk fat 18:0, cis-9 18:1, LA, and ALA concentrations. Milk fat 18:0 was low
      (<5g/100g of FA) across all treatments. Increases in CO linearly decreased the
      proportions of total saturates from 58 to 45g/100g of FA and linearly enriched
      trans-11 18:1, cis-9,trans-11 18:2, and trans-11,cis-15 18:2 from 5.2, 2.6, and
      1.7 to 11, 4.3, and 5.8g/100g of FA, respectively. Furthermore, CO quadratically
      decreased milk fat trans-10 18:1 and linearly decreased trans-10,cis-12 18:2
      concentration. Overall, milk FA composition on all treatments suggested that one
      or more components in camelina seeds may inhibit the complete reduction of 18
      carbon unsaturates in the rumen. In conclusion, CO decreased the secretion of
      saturated FA in milk and increased those of the trans-11 biohydrogenation pathway
      or their desaturation products. Despite increasing the intake of 18-carbon
      unsaturated FA, CO had no effect on the secretions of 18:0, cis-9 18:1, LA, or
      ALA in milk. Concentrates containing camelina expeller and 2% CO could be used
      for the commercial production of low-saturated milk from grass- and RCS-based
      diets without major adverse effects on animal performance.

PMID- 27865510
TI  - Electrophoretic characterization of protein interactions suggesting limited
      feasibility of accelerated shelf-life testing of ultra-high temperature milk.
AB  - Accelerated shelf-life testing is applied to a variety of products to estimate
      keeping quality over a short period of time. The industry has not been successful
      in applying this approach to ultra-high temperature (UHT) milk because of
      chemical and physical changes in the milk proteins that take place during
      processing and storage. We investigated these protein changes, applying
      accelerated shelf-life principles to UHT milk samples with different fat levels
      and using native- and sodium dodecyl sulfate-PAGE. Samples of UHT skim and whole
      milk were stored at 20, 30, 40, and 50 degrees C for 28d. Irrespective of fat
      content, UHT treatment had a similar effect on the electrophoretic patterns of
      milk proteins. At the start of testing, proteins were bonded mainly through
      disulfide and noncovalent interactions. However, storage at and above 30 degrees
      C enhanced protein aggregation via covalent interactions. The extent of
      aggregation appeared to be influenced by fat content; whole milk contained more
      fat than skim milk, implying aggregation via melted or oxidized fat, or both.
      Based on reduction in loss in absolute quantity of individual proteins, covalent
      crosslinking in whole milk was facilitated mainly by products of lipid oxidation
      and increased access to caseins for crosslinking reactions. Maillard and
      dehydroalanine products were the main contributors involved in protein changes in
      skim milk. Protein crosslinking appeared to follow a different pathway at higher
      temperatures (>=40 degrees C) than at lower temperatures, making it very
      difficult to extrapolate these changes to protein interactions at lower
      temperatures.

PMID- 27865511
TI  - Modeling genetic and nongenetic variation of feed efficiency and its partial
      relationships between component traits as a function of management and
      environmental factors.
AB  - Feed efficiency (FE), characterized as the fraction of feed nutrients converted
      into salable milk or meat, is of increasing economic importance in the dairy
      industry. We conjecture that FE is a complex trait whose variation and
      relationships or partial efficiencies (PE) involving the conversion of dry matter
      intake to milk energy and metabolic body weight may be highly heterogeneous
      across environments or management scenarios. In this study, a hierarchical
      Bayesian multivariate mixed model was proposed to jointly infer upon such
      heterogeneity at both genetic and nongenetic levels on PE and variance components
      (VC). The heterogeneity was modeled by embedding mixed effects specifications on
      PE and VC in addition to those directly specified on the component traits. We
      validated the model by simulation and applied it to a joint analysis of a dairy
      FE consortium data set with 5,088 Holstein cows from 13 research stations in
      Canada, the Netherlands, the United Kingdom, and the United States. Although no
      differences were detected among research stations for PE at the genetic level,
      some evidence was found of heterogeneity in residual PE. Furthermore, substantial
      heterogeneity in VC across stations, parities, and ration was observed with
      heritability estimates of FE ranging from 0.16 to 0.46 across stations.

PMID- 27865512
TI  - The effect of supplemental concentrate fed during the dry period on morphological
      and functional aspects of rumen adaptation in dairy cattle during the dry period
      and early lactation.
AB  - Ten rumen-cannulated Holstein-Friesian cows were used to examine the effect of
      feeding supplemental concentrate during the dry period on rumen papillae
      morphology and fractional absorption rate (ka) of volatile fatty acids (VFA)
      during the dry period and subsequent lactation. Treatment consisted of
      supplemental concentrate [3.0kg of dry matter (DM)/d] from 28d antepartum (ap)
      until the day of calving, whereas control did not receive supplemental
      concentrate. Cows were fed for ad libitum intake and had free access to the dry
      period ration (27% grass silage, 28% corn silage, 35% wheat straw, and 11%
      soybean meal on a DM basis) and, from calving onward, to a basal lactation ration
      (42% grass silage, 42% corn silage, and 16% soybean meal on a DM basis). From 1
      to 3d postpartum (pp), all cows were fed 0.9kg DM/d of concentrate, which
      increased linearly thereafter to 8.9kg of DM/d on d 11 pp. At 28, 18, and 8d ap,
      and 3, 17, 31, and 45d pp, rumen papillae were collected and kaVFA was measured
      in all cows. On average, 13.8 (standard deviation: 3.8) papillae were collected
      each from the ventral, caudodorsal, and caudoventral rumen sacs per cow per day.
      The kaVFA was measured by incubating a standardized buffer fluid (45 L),
      containing 120mM VFA (60% acetic, 25% propionic, and 15% butyric acid) and Co
      EDTA as fluid passage marker, in the evacuated and washed rumen. Treatment did
      not affect ap or pp DM and energy intakes or milk yield and composition.
      Treatment increased papillae surface area, which was 19 and 29% larger at 18 and
      8d ap compared with 28d ap, respectively. Surface area increased, mainly due to
      an increase in papillae width. However, treatment did not increase kaVFA at 18
      and 8d ap compared with 28d ap. In the control group, no changes in papillae
      surface area or kaVFA were observed during the dry period. In the treatment
      group, papillae surface area decreased between 8d ap and 3d pp, whereas no
      decrease was observed for control. From 3 to 45d pp, papillae surface area and
      kaVFA increased for all cows by approximately 50%, but the ap concentrate
      treatment did not affect kaVFA pp. In conclusion, the efficacy of supplemental
      concentrate during the dry period to increase papillae surface area and kaVFA in
      preparation for subsequent lactation is not supported by the present study.
      Current observations underline the importance of functional measurements in lieu
      of morphological measurements to assess changes in the adapting rumen wall.

PMID- 27865513
TI  - The effect of milk allowance on behavior and weight gains in dairy calves.
AB  - The objective of this study was to investigate how milk allowance affects body
      weight gains and behavior before, during, and after weaning in dairy calves.
      Fifty-six Holstein calves were randomly assigned at 1wk of age to 1 of 4 feeding
      treatments of whole pasteurized milk: 6, 8, 10, or 12 L/d. Milk allowance was
      reduced by 50% at d 42, and then reduced by 20% per day starting at d 50, so that
      calves were completely weaned at d 55. Calves were provided ad libitum access to
      calf starter and hay. Body weight was measured weekly from 2 to 10wk of age. Milk
      intake increased with milk allowance as intended, although actual intakes were
      lower than the treatment allowance (e.g., averaging 5.66+/-0.19 L on the 6-L
      treatment and 9.41+/-0.21 L on the 12-L treatment before weaning). Intake of calf
      starter was higher for calves that were fed less milk before weaning (averaging
      0.25+/-0.03kg/d and 0.05+/-0.03kg/d on the 6-L and 12-L treatments, respectively)
      and also during the weaning period (averaging 1.15+/-0.13kg/d and 0.54+/-0.14kg/d
      on these same treatments), but we observed no effect after weaning. Time spent at
      the hay feeder did not differ with treatment. Average daily gain was higher for
      calves that were fed more milk, increasing from 0.77+/-0.04kg/d with the 6-L
      treatment to 0.90+/-0.03kg/d with the 12-L treatment. Before weaning, calves fed
      less milk engaged in more unrewarded visits to the milk feeder, averaging 11.1+/
      0.73 visits/d with the 6-L treatment and 0.4+/-0.78 visits/d with the 12-L
      treatment. During weaning, calves fed less milk still had more unrewarded visits
      to the milk feeder than calves fed more milk (19.7+/-1.64 visits/d with the 6-L
      treatment versus 10.1+/-1.74 visits/d with the 12-L treatment), but treatments
      did not differ after weaning. We conclude that higher milk allowances result in
      weight gain advantages before weaning that can persist beyond weaning, and that
      the high number of unrewarded visits to the milk feeder by calves that were fed
      less milk are indicative of persistent hunger.

PMID- 27865514
TI  - Coagulase-negative Staphylococcus species in bulk milk: Prevalence, distribution,
      and associated subgroup- and species-specific risk factors.
AB  - Coagulase-negative staphylococci (CNS) have become the main pathogens causing
      bovine mastitis in recent years. A huge variation in species distribution among
      herds has been observed in several studies, emphasizing the need to identify
      subgroup- and species-specific herd-level factors to improve our understanding of
      the differences in ecological and epidemiological nature between species. The use
      of bulk milk samples enables the inclusion of a large(r) number of herds needed
      to identify herd-level risk factors and increases the likelihood of recovering
      enough isolates per species needed for conducting subgroup- and, eventually,
      species-specific analyses at the same time. This study aimed to describe the
      prevalence and distribution of CNS species in bulk milk samples and to identify
      associated subgroup- and species-specific herd-level factors. Ninety percent of
      all bulk milk samples yielded CNS. Staphylococcus equorum was the predominant
      species, followed by Staphylococcus haemolyticus and Staphylococcus epidermidis.
      A seasonal effect was observed for several CNS species. Bulk milk samples from
      herds with a loose-pack or a tiestall housing system were more likely to yield
      CNS species compared with herds with a freestall barn, except for S. epidermidis,
      Staphylococcus simulans, and Staphylococcus cohnii. In September, herds in which
      udders were clipped had lower odds of yielding Staphylococcus chromogenes, S.
      simulans, and Staphylococcus xylosus, the CNS species assumed to be most relevant
      for udder health, in their bulk milk than herds in which udder clipping was not
      practiced. Bulk milk of herds participating in a monthly veterinary udder health
      monitoring program was more likely to yield these 3 CNS species. Herds always
      receiving their milk quality premium or predisinfecting teats before attachment
      of the milking cluster had lower odds of having S. equorum in their bulk milk.
      Herds not using a single dry cotton or paper towel for each cow during premilking
      udder preparation were more likely to have S. cohnii-positive bulk milk. Herds in
      which flushing with hot water or steam of the milking cluster after having milked
      a cow with a (sub)clinical mastitis was applied, were less likely to yield S.
      simulans, S. haemolyticus, and S. cohnii in their bulk milk. Always wearing
      gloves during milking decreased the odds of having Staphylococcus devriesei
      positive bulk milk. Tap water from the public drinking system used as drinking
      water increased the odds of yielding S. simulans in the bulk milk. In conclusion,
      CNS are highly prevalent in bulk milk and might originate from the environment
      for some species (we hypothesize this is true for S. equorum or S. cohnii), or
      from within the udder (e.g., for S. simulans). Studies collecting bulk milk and
      quarter milk samples at the same time along with environmental samples are needed
      to determine the exact origin of the different (subgroups of) CNS species present
      in bulk milk using strain-typing techniques.

PMID- 27865515
TI  - [Bladder tumor histoseminar - Case 7: Primary urothelial adenocarcinoma].

PMID- 27865516
TI  - Headholders' - complications in neurosurgery: A review of the literature and
      recommendations for its use.
AB  - Several types of headholders are routinely used in neurosurgical practice to
      secure the head in a precise position, providing better security during surgical
      dissection as well as an absence of eye compression during prone positions.
      Nevertheless, potentially lethal complications might occur. We performed a review
      of the literature via PubMed and Google Scholar using the terms "Mayfield skull
      clamp", "Sugita headholders", "headholder complications" and "skull clamp
      complications". Twenty-six complications directly related to the use of
      headholders were identified through 19 papers published from 1981 to 2014: mainly
      skull fractures with or without a dural laceration (50%), epidural hematomas
      (23.8%), skull fractures with or without a dural laceration (50%), and air
      embolism (9.5%). The authors propose recommendations for the safe use of
      headholders.

PMID- 27865517
TI  - Effects of melatonin in the treatment of asthenia in aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND OBJECTIVES: Survivors of aneurysmal subarachnoid hemorrhage (aSAH)
      commonly experience sleep disorders resulting in asthenia. The objective of this
      prospective study was to determine, in a cohort of patients with treated ruptured
      intracranial aneurysm (IA), the proportion of asthenia at 2months, in a cohort of
      patients treated with melatonin and in a control cohort. PATIENTS AND METHODS:
      Twenty consecutive patients admitted for the treatment of ruptured IA and able to
      answer a standardized questionnaire were included in the study. After evaluation
      for fatigue at discharge, we divided our population into 2 cohorts of 10
      patients: the first cohort was treated with melatonin for a period of 2months;
      the second cohort had no specific treatment for fatigue. The primary endpoint was
      the proportion of asthenia at 2months in both groups. Confounding factors, such
      as depression, autonomy and apathy were evaluated at the same time. RESULTS: At
      discharge, there was no significant difference observed between both groups in
      terms of mean age and initial clinical status (WFNS, Rankin Scale and Fatigue
      Severity Scale). At 2months, the mean FSS score in the control group was of 4.7+/
      1.0 versus 3.8+/-0.9 in the melatonin group (P=0.03). The mean MADRS score in the
      control group was of 1.1+/-1.45 versus 2.7+/-2.5 in the melatonin group (P=0.10).
      The mean LARS score in the control group was of -32.5+/-1.7 versus -31.7+/-1.9 in
      the melatonin group (P=0.24). DISCUSSION: In a prospective evaluation of post
      aSAH fatigue, we suggest that melatonin could decrease fatigue. There is no
      significant impact on depression and apathy. Further studies would be necessary
      to improve our comprehension of fatigue physiopathology in a context of aSAH.

PMID- 27865518
TI  - Impact of surgical correction of a U-shaped sacral fracture on sagittal spino
      pelvic alignment: Regarding one case.
AB  - U-shaped sacral fractures are uncommon and are mostly the consequence of a high
      energy kinetic trauma. The sacrum is a crucial element for sagittal alignment in
      a standing position as it determines the value of the pelvic incidence, which is
      a fixed and unchanging parameter for a given individual. We report the case of a
      21-year-old man who underwent corrective surgery for a type II U-shaped fracture
      of the sacrum (according to the Roy-Camille classification), associated with a S1
      S2 dislocation and sacral kyphosis that modified the patient's pelvic incidence.
      At one-year follow-up, radiographic examinations revealed solid bony fusion and
      stable results after removal of the implants. The surgery was managed for
      neurological decompression, stabilization of the fracture and correction of
      sacral kyphosis. The restoration of the theoretical pelvic incidence depended on
      the estimated lumbar lordosis. The aim of this study was to highlight the
      particularities in the management of a sacral U-shaped fracture and their
      relationship with the sagittal alignment.

PMID- 27865519
TI  - Fine sediments suppress detritivory on coral reefs.
AB  - Increasing sediment inputs are recognised as an important factor leading to coral
      reef degradation. However, the role of sediments in ecological processes is
      poorly understood. This study used paired-choice trials to quantify the effects
      of sediment grain size and chemical composition on feeding by the abundant
      detritivorous reef fish, Ctenochaetus striatus. The size of sediments from algal
      turfs were also compared to those ingested by reef-dwelling C. striatus. Algal
      turfs containing coarser sediments were preferred by C. striatus, while sediment
      composition (reefal carbonates vs. riverine silicates) had little effect. On the
      reef, C. striatus ingested finer sediments than those present in algal turfs. C.
      striatus appears to prefer algal turfs with coarser sediments as this facilitates
      ingestion of fine detrital particles, while finer sediments prevent selective
      feeding on detritus. These findings suggest that fine sediments from terrestrial
      runoff or dredging may be detrimental to feeding by detritivorous species.

PMID- 27865520
TI  - Are environmental risk estimations linked to the actual environmental impact?
      Application to an oil handling facility (NE Spain).
AB  - The environmental risk analysis of aquatic systems includes the evaluation of the
      likelihood that adverse ecological effects may occur as a result of exposure to
      one or more stressors. In harbor areas, pollution is provided by a complex
      mixture of substances with different levels of toxicity, persistence and
      bioaccumulation, which complicates the hazards characterization and their
      multiple effects. A study of the relationship between the environmental impact
      and the environmental risk assessment at a specific isolated oil handling
      facility was undertaken. The environmental risk of the oil handling facility,
      considering the consequences of specific pollutants, was estimated and the
      associated environmental impact was quantified based on a 'weights of evidence'
      approach. The contamination quantified at the potentially affected area around
      the monobuoy of Tarragona has proved to be related with environmental risk
      estimations but the lines of evidence obtained do not allow us to assert that the
      activity developed at this facility has an associated environmental impact.

PMID- 27865521
TI  - Degradation pathways of 1-methylphenanthrene in bacterial Sphingobium sp. MP9-4
      isolated from petroleum-contaminated soil.
AB  - Alkylated polycyclic aromatic hydrocarbons (PAHs) are abundant in petroleum, and
      alkylated phenanthrenes are considered as the primary PAHs during some oil spill
      events. Bacterial strain of Sphingobium sp. MP9-4, isolated from petroleum
      contaminated soil, was efficient to degrade 1-methylphenanthrene (1-MP). A
      detailed metabolism map of 1-MP in this strain was delineated based on analysis
      of metabolites with gas chromatograph-mass spectrometer (GC-MS). 1-MP was
      initially oxidized via two different biochemical strategies, including benzene
      ring and methyl-group attacks. Benzene ring attack was initiated with
      dioxygenation of the non-methylated aromatic ring via similar degradation
      pathways of phenanthrene (PHE) by bacteria. For methyl-group attack, mono
      oxygenase system was involved and more diverse enzymes were needed than that of
      PHE degradation. This study enhances the understanding of the metabolic pathways
      of alkylated PAHs and shows the significant potential of Sphingobium sp. MP9-4
      for the bioremediation of alkylated PAHs contaminated environments.

PMID- 27865522
TI  - Pollution levels and risks of polycyclic aromatic hydrocarbons in surface
      sediments from two typical estuaries in China.
AB  - To assess the environmental risks of polycyclic aromatic hydrocarbons (PAHs), 48
      and 45 sediments were collected from the Yangtze River Estuary (YRE) and Pearl
      River Estuary (PRE), respectively. The toxicity equivalency concentration (TEQ)
      in the YRE and PRE were ranged from 1.68 to 76.13 and 9.28 to 129.24ngTEQg-1,
      respectively. Results of risk quotient suggest that ecological risks of two
      estuaries are at a moderate level, but are higher in the PRE than YRE. The
      increment lifetime cancer risks (ILCR) from the YRE via ingestion and dermal
      contact were 1*10-6 to 5.6*10-5 and 4*10-6 to 1.6*10-4, and ranged from 7*10-6 to
      9.4*10-5 and 2*10-5 to 2.8*10-4 in the PRE. ILCR results suggest that some low
      and moderate cancer risk exists in the YRE and PRE. Therefore, monitoring and
      control measures should be carried out immediately to reduce or eliminate the
      risks to human health from environmental exposure.

PMID- 27865524
TI  - Exposure to UV filters during summer and winter in Danish kindergarten children.
AB  - BACKGROUND: Ultra violet (UV) filters with known or suspected endocrine
      disrupting properties are widely used in sunscreens and other personal care
      products, clothing, food packaging and many other consumer products. Danish
      kindergarten children have sunscreens applied daily during summer to prevent skin
      burns. OBJECTIVES: To estimate the assumed contribution of sunscreens to the
      total exposure to UV filters, we measured the urinary excretion of UV filters
      during summer and winter in kindergarten children. METHODS: Spot- and first
      morning urines were collected during a summer and a winter day in 2013. A total
      of 266 urine samples were collected from 55 children and were analysed for
      content of benzophenone (BP), benzophenone-1 (BP-1), benzophenone-2 (BP-2),
      benzophenone-3 (BP-3), 5-chloro-2-hydroxybenzophenone (BP-7), 4-methyl
      benzophenone (4-MBP), 4-hydroxybenzophenone (4-HBP), 3-(4-methylbenzylidene)
      camphor (4-MBC), and 3-benzylidene camphor (3-BC) by LC-MS/MS. RESULTS: Of the
      analysed UV filters, the children excreted predominantly BP-1, BP-3 and 4-HBP.
      The urine levels were significantly higher in summer samples compared to winter
      samples, however exposure during winter was still evident. Furthermore, children
      with the highest concentrations of UV filters in summer urines also tended to be
      among those with the highest winter levels. CONCLUSION: Exposures to UV filters
      during summertime can partly be explained by the intended use of UV filters in
      sunscreens, which is considered to be beneficial for children during outdoor
      activities. However, exposure to UV filters all year round together with large
      inter-individual variation indicate that children's exposure to UV filters also
      comes from other consumer items, presumably highly influenced by the general
      lifestyle of an individual child: this is completely unintended, without benefit,
      and potentially harmful.

PMID- 27865523
TI  - Alterations in high-density lipoprotein proteome and function associated with
      persistent organic pollutants.
AB  - There is a growing body of evidence that persistent organic pollutants (POPs) may
      increase the risk for cardiovascular disease (CVD), but the mechanisms remain
      unclear. High-density lipoprotein (HDL) acts protective against CVD by different
      processes, and we have earlier found that HDL from subjects with CVD contains
      higher levels of POPs than healthy controls. In the present study, we have
      expanded analyses on the same individuals living in a contaminated community and
      investigated the relationship between the HDL POP levels and protein
      composition/function. HDL from 17 subjects was isolated by ultracentrifugation.
      HDL protein composition, using nanoliquid chromatography tandem mass
      spectrometry, and antioxidant activity were analyzed. The associations of 16
      POPs, including polychlorinated biphenyls (PCBs) and organochlorine pesticides,
      with HDL proteins/functions were investigated by partial least square and
      multiple linear regression analysis. Proteomic analyses identified 118 HDL
      proteins, of which ten were significantly (p<0.05) and positively associated with
      the combined level of POPs or with highly chlorinated PCB congeners. Among these,
      cholesteryl ester transfer protein and phospholipid transfer protein, as well as
      the inflammatory marker serum amyloid A, were found. The serum
      paraoxonase/arylesterase 1 activity was inversely associated with POPs. Pathway
      analysis demonstrated that up-regulated proteins were associated with biological
      processes involving lipoprotein metabolism, while down-regulated proteins were
      associated with processes such as negative regulation of proteinases, acute phase
      response, platelet degranulation, and complement activation. These results
      indicate an association between POP levels, especially highly chlorinated PCBs,
      and HDL protein alterations that may result in a less functional particle.
      Further studies are needed to determine causality and the importance of other
      environmental factors. Nevertheless, this study provides a first insight into a
      possible link between exposure to POPs and risk of CVD.

PMID- 27865526
TI  - Emerging usage of electrocoagulation technology for oil removal from wastewater:
      A review.
AB  - Electrocoagulation is a simple and efficient treatment method involving the
      electrodissolution of sacrificial anodes and formation of hydroxo-metal products
      as coagulants, while the simultaneous production of hydrogen at the cathode
      facilitates the pollutant removal by flotation. Oil is one of the most important
      hydrocarbon products in the modern world. It can cause environmental pollution
      during various stages of production, transportation, refining and use.
      Electrocoagulation treatment is particularly effective for destabilization of oil
      in-water emulsions by neutralizing charges and bonding oil pollutants to
      generated flocs and hydrogen bubbles. The development of electrocoagulation
      technologies provided a promising alternative for oil removal from wastewater.
      This paper presents a review of emerging electrochemical technologies used for
      treating oil-containing wastewater. It includes a brief description of the oily
      wastewater origin and characteristics. The treatment processes developed so far
      for oily wastewater and the electrocoagulation mechanisms are also introduced.
      This paper summarizes the current applications of electrocoagulation for oil
      removal from wastewater. The factors that influence the electrocoagulation
      treatment efficiencies as well as the process optimization and modeling studies
      are discussed. The state-of-the-art and development trends of electrocoagulation
      process for oil removal are further introduced.

PMID- 27865525
TI  - Maternal stress modifies the effect of exposure to lead during pregnancy and 24
      month old children's neurodevelopment.
AB  - BACKGROUND: Lead and psychosocial stress disrupt similar but not completely
      overlapping mechanisms. Exposure during the prenatal period to each of these
      insults singularly has been found to alter normal neurodevelopment; however,
      longitudinal associations with stress modifying the effect of lead have not been
      sufficiently analyzed in epidemiologic studies. OBJECTIVE: To evaluate prenatal
      stress as an effect modifier of gestational lead neurotoxicity. METHODS: We used
      a structural equations modeling approach with a trivariate response to evaluate
      cognitive, language and motor scores of the Bayley Scales of Infant Development
      III in 24month-old children (n=360). Maternal blood lead levels were measured at
      the 2nd and 3rd trimester and psychosocial stress during pregnancy was assessed
      using a negative life events (NLE) scale derived from the CRYSIS questionnaire.
      RESULTS: 3rd trimester lead (mean 3.9+/-3.0 SDMUg/dL) and stress (median=3 NLE)
      were negatively associated with Bayley III scores. Using the model's results we
      generated profiles for 0, 2, 4 and 6 NLE across lead levels (up to 10MUg/dL) and
      observed a dose-response for the developmental scores when lead levels were below
      2MUg/dL. Each NLE curve had a different shape across increasing lead levels.
      Higher stress (NLE=6) resulted in lower cognitive scores for both sexes, in lower
      language scores in girls but not boys. In the absence of stress we saw a negative
      association with lead for all scores, however for language and motor scores,
      higher stress seemed to mask this association. CONCLUSIONS: Our work examined and
      confirmed prenatal stress exposure as a modifier of the well-known neurotoxic
      effects of prenatal lead. It adds to the existing evidence pointing at the
      importance of studying the co-exposure of chemical and non-chemical exposures,
      specifically of considering the emotional environment of children at early
      developmental stages of life.

PMID- 27865527
TI  - Pathways of inhalation exposure to manganese in children living near a
      ferromanganese refinery: A structural equation modeling approach.
AB  - Manganese (Mn) is both essential element and neurotoxicant. Exposure to Mn can
      occur from various sources and routes. Structural equation modeling was used to
      examine routes of exposure to Mn among children residing near a ferromanganese
      refinery in Marietta, Ohio. An inhalation pathway model to ambient air Mn was
      hypothesized. Data for model evaluation were obtained from participants in the
      Communities Actively Researching Exposure Study (CARES). These data were
      collected in 2009 and included levels of Mn in residential soil and dust, levels
      of Mn in children's hair, information on the amount of time the child spent
      outside, heat and air conditioning in the home and level of parent education.
      Hair Mn concentration was the primary endogenous variable used to assess the
      theoretical inhalation exposure pathways. The model indicated that household dust
      Mn was a significant contributor to child hair Mn (0.37). Annual ambient air Mn
      concentration (0.26), time children spent outside (0.24) and soil Mn (0.24)
      significantly contributed to the amount of Mn in household dust. These results
      provide a potential framework for understanding the inhalation exposure pathway
      for children exposed to ambient air Mn who live in proximity to an industrial
      emission source.

PMID- 27865528
TI  - Integrating new indicators of predictors that shape the public's perception of
      local extreme temperature in China.
AB  - The public's risk perception of local extreme heat or cold plays a critical role
      in community health and prevention under climate change. However, there is
      limited evidence on such issues in China where extreme weather is occurring more
      frequently due to climate change. Here, a total of 2500 residents were selected
      using a three-step sampling method and investigated by a questionnaire in two
      representative cities. We investigated risk perception of extreme heat in Beijing
      and extreme cold in Harbin in 2013, aiming to examine their possible correlations
      with multiple epidemiological factors. We found that exposure, vulnerability, and
      adaptive ability were significant predictors in shaping public risk perceptions
      of local extreme temperature. In particular, a 1 degrees C increase in daily
      temperature resulted in an increased odds of perceiving serious extreme heat in
      Beijing (OR=1.091; 95% CI: 1.032, 1.153), while a 1 degrees C increase in daily
      temperature resulted in a decreased odds of perceiving serious extreme cold in
      Harbin (OR=0.965; 95% CI: 0.939, 0.992). Therefore for both extreme heat and
      cold, frequent local extreme temperature exposure may amplify a stronger
      communication. Health interventions for extreme temperature should consider
      exposure, vulnerability, and adaptive ability factors. This will help improve the
      public's perception of climatic changes and their willingness to balance adaption
      and mitigation appropriately.

PMID- 27865530
TI  - Cardiac function and survival are affected by crude oil in larval red drum,
      Sciaenops ocellatus.
AB  - Following exposure to weathered and non-weathered oil, lethal and sub-lethal
      impacts on red drum larvae were assessed using survival, morphological, and
      cardiotoxicity assays. The LC50 for red drum ranged from 14.6 (10.3-20.9) to 21.3
      (19.1-23.8) MUgl-1 SigmaPAH with no effect of exposure timing during the pre
      hatch window or oil weathering. Similarly, morphological deformities showed dose
      responses in the low ppb range. Cardiac output showed similar sensitivity
      resulting in a major 70% reduction after exposure to 2.6MUgl-1 SigmaPAH. This
      cardiac failure was driven by reduced stroke volume rather than bradycardia,
      meaning that in some species, cardiac function is more sensitive than previously
      thought. After the Deepwater Horizon oil spill, much of this type of work has
      primarily focused on pelagic species with little known about fast developing
      estuarine species. These results demonstrate similarity sensitivity of the red
      drum as their pelagic counter parts, and more importantly, that cardiac function
      is dramatically reduced in concert with pericardial edema.

PMID- 27865529
TI  - Application of acclimated sewage sludge as a bio-augmentation/bio-stimulation
      strategy for remediating chlorpyrifos contamination in soil with/without cadmium.
AB  - This experiment was performed to investigate the effects of acclimated sewage
      sludge (ASS) and sterilized ASS on the fates of chlorpyrifos (CP) in soil with or
      without cadmium (Cd), as well as the improvement of soil biochemical properties.
      Results showed that both ASS and sterilized ASS could significantly promote CP
      dissipation, and the groups with ASS had the highest efficiency on CP removal,
      whose degradation rates reached 71.3%-85.9% at the 30th day (40.4%-50.2% higher
      than non-sludge groups). Besides, the degradation rate of CP was not severely
      influenced by the existence of Cd, and the population of soil microorganism
      dramatically increased after adding sludge. The soil enzyme activities
      (dehydrogenase, acid phosphatase and FDA hydrolase activities) ranked from high
      to low were as follows: groups with sterilized ASS>groups with ASS>groups without
      sludge. Simultaneously, 16S rRNA gene sequencing revealed that ASS changed
      bacterial community structure and diversity in soil. In addition, alkali
      hydrolyzable nitrogen and Olsen- phosphorus increased after application of
      sludge, indicating that the addition of ASS (or sterilized ASS) could effectively
      improve soil fertility.

PMID- 27865531
TI  - Meeting Our Patients Where They Are.

PMID- 27865533
TI  - Prince Mahidol Awards for 2016 announced.

PMID- 27865532
TI  - Tarp-Assisted Cooling as a Method of Whole-Body Cooling in Hyperthermic
      Individuals.
AB  - STUDY OBJECTIVE: We investigated the efficacy of tarp-assisted cooling as a body
      cooling modality. METHODS: Participants exercised on a motorized treadmill in hot
      conditions (ambient temperature 39.5 degrees C [103.1 degrees F], SD 3.1 degrees
      C [5.58 degrees F]; relative humidity 38.1% [SD 6.7%]) until they reached
      exercise-induced hyperthermia. After exercise, participants were cooled with
      either partial immersion using a tarp-assisted cooling method (water temperature
      9.20 degrees C [48.56 degrees F], SD 2.81 degrees C [5.06 degrees F]) or passive
      cooling in a climatic chamber. RESULTS: There were no differences in exercise
      duration (mean difference=0.10 minutes; 95% CI -5.98 to 6.17 minutes or end
      exercise rectal temperature (mean difference=0.10 degrees C [0.18 degrees F]; 95%
      CI -0.05 degrees C to 0.25 degrees C [-0.09 degrees F to 0.45 degrees F] between
      tarp-assisted cooling (48.47 minutes [SD 8.27 minutes]; rectal temperature 39.73
      degrees C [103.51 degrees F], SD 0.27 degrees C [0.49 degrees F]) and passive
      cooling (48.37 minutes [SD 7.10 minutes]; 39.63 degrees C [103.33 degrees F], SD
      0.40 degrees C [0.72 degrees F]). Cooling time to rectal temperature 38.25
      degrees C (100.85 degrees F) was significantly faster in tarp-assisted cooling
      (10.30 minutes [SD 1.33 minutes]) than passive cooling (42.78 [SD 5.87 minutes]).
      Cooling rates for tarp-assisted cooling and passive cooling were 0.17 degrees
      C/min (0.31 degrees F/min), SD 0.07 degrees C/min (0.13 degrees F/min) and 0.04
      degrees C/min (0.07 degrees F/min), SD 0.01 degrees C/min (0.02 degrees F/min),
      respectively (mean difference=0.13 degrees C [0.23 degrees F]; 95% CI 0.09
      degrees C to 0.17 degrees C [0.16 degrees F to 0.31 degrees F]. No sex
      differences were observed in tarp-assisted cooling rates (men 0.17 degrees C/min
      [0.31 degrees F/min], SD 0.07 degrees C/min [0.13 degrees F/min]; women 0.16
      degrees C/min [0.29 degrees F/min], SD 0.07 degrees C/min [0.13 degrees F/min];
      mean difference=0.02 degrees C/min [0.04 degrees F/min]; 95% CI -0.06 degrees
      C/min to 0.10 degrees C/min [-0.11 degrees F/min to 0.18 degrees F/min]). Women
      (0.04 degrees C/min [0.07 degrees F/min], SD 0.01 degrees C/min [0.02 degrees
      F/min]) had greater cooling rates than men (0.03 degrees C/min [0.05 degrees
      F/min], SD 0.01 degrees C/min [0.02 degrees F/min]) in passive cooling, with
      negligible clinical effect (mean difference=0.01 degrees C/min [0.02 degrees
      F/min]; 95% CI 0.001 degrees C/min to 0.024 degrees C/min [0.002 degrees F/min to
      0.04 degrees F/min]). Body mass was moderately negatively correlated with the
      cooling rate in passive cooling (r=-0.580) but not in tarp-assisted cooling (r=
      0.206). CONCLUSION: In the absence of a stationary cooling method such as cold
      water immersion, tarp-assisted cooling can serve as an alternative, field
      expedient method to provide on-site cooling with a satisfactory cooling rate.

PMID- 27865534
TI  - Meniere's disease: damaged hearing but reduced vertigo.

PMID- 27865535
TI  - Intratympanic methylprednisolone versus gentamicin in patients with unilateral
      Meniere's disease: a randomised, double-blind, comparative effectiveness trial.
AB  - BACKGROUND: Meniere's disease is characterised by severe vertigo attacks and
      hearing loss. Intratympanic gentamicin, the standard treatment for refractory
      Meniere's disease, reduces vertigo, but damages vestibular function and can
      worsen hearing. We aimed to assess whether intratympanic administration of the
      corticosteroid methylprednisolone reduces vertigo compared with gentamicin.
      METHODS: In this double-blind comparative effectiveness trial, patients aged 18
      70 years with refractory unilateral Meniere's disease were enrolled at Charing
      Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK).
      Patients were randomly assigned (1:1) by a block design to two intratympanic
      methylprednisolone (62.5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks
      apart, and were followed up for 2 years. All investigators and patients were
      masked to treatment allocation. The primary outcome was vertigo frequency over
      the final 6 months (18-24 months after injection) compared with the 6 months
      before the first injection. Analyses were done in the intention-to-treat
      population, and then per protocol. This trial is registered with
      ClinicalTrials.gov, number NCT00802529. FINDINGS: Between June 19, 2009, and
      April 15, 2013, 256 patients with Meniere's disease were screened, 60 of whom
      were enrolled and randomly assigned: 30 to gentamicin and 30 to
      methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the
      mean number of vertigo attacks in the final 6 months compared with the 6 months
      before the first injection (primary outcome) decreased from 19.9 (SD 16.7) to 2.5
      (5.8) in the gentamicin group (87% reduction) and from 16.4 (12.5) to 1.6 (3.4)
      in the methylprednisolone group (90% reduction; mean difference -0.9, 95% CI -3.4
      to 1.6). Patients whose vertigo did not improve after injection (ie, non
      responders) after being assessed by an unmasked clinician were eligible for
      additional injections given by a masked clinician (eight patients in the
      gentamicin group vs 15 in the methylprednisolone group). Two non-responders
      switched from methylprednisolone to gentamicin. Both drugs were well tolerated
      with no safety concerns. Six patients reported one adverse event each: three in
      the gentamicin group and three in the methylprednisolone group. The most common
      adverse event was minor ear infections, which was experienced by one patient in
      the gentamicin group and two in the methylprednisolone group. INTERPRETATION:
      Methylprednisolone injections are a non-ablative, effective treatment for
      refractory Meniere's disease. The choice between methylprednisolone and
      gentamicin should be made based on clinical knowledge and patient circumstances.
      FUNDING: Meniere's Society and National Institute for Health Research Imperial
      Biomedical Research Centre.

PMID- 27865536
TI  - Breast cancer.
AB  - Breast cancer is one of the three most common cancers worldwide. Early breast
      cancer is considered potentially curable. Therapy has progressed substantially
      over the past years with a reduction in therapy intensity, both for locoregional
      and systemic therapy; avoiding overtreatment but also undertreatment has become a
      major focus. Therapy concepts follow a curative intent and need to be decided in
      a multidisciplinary setting, taking molecular subtype and locoregional tumour
      load into account. Primary conventional surgery is not the optimal choice for all
      patients any more. In triple-negative and HER2-positive early breast cancer,
      neoadjuvant therapy has become a commonly used option. Depending on clinical
      tumour subtype, therapeutic backbones include endocrine therapy, anti-HER2
      targeting, and chemotherapy. In metastatic breast cancer, therapy goals are
      prolongation of survival and maintaining quality of life. Advances in endocrine
      therapies and combinations, as well as targeting of HER2, and the promise of
      newer targeted therapies make the prospect of long-term disease control in
      metastatic breast cancer an increasing reality.

PMID- 27865537
TI  - Metastases in the cervical spine from primary head and neck cancers: current
      concepts of diagnosis and management.
AB  - Vertebral metastases from primary head and neck cancers are uncommon, and so
      there are no clear guidelines about management. The spinal cord can be compressed
      by a vertebral fracture or invasion of a tumour, and may present as an
      oncological and spinal emergency. The goals of treatment are to relieve pain and
      maintain neurological function. However, surgical treatments in this group of
      patients have not been defined, and primary operative treatment of spinal
      metastases remains controversial. Here we discuss their contemporary management.
      Surgical options should be considered for treatment to achieve stability of the
      spine, relieve pain, and preserve neurological function in certain cases.

PMID- 27865538
TI  - Micafungin in the treatment of invasive fungal infection in an infant with
      extracorporeal.

PMID- 27865539
TI  - Meta-analysis of prevalence of wheezing and recurrent wheezing in infants.
AB  - BACKGROUND: Wheezing affects children's quality of life, and is related with
      asthma in childhood. Although prevalence of wheezing has been previously studied
      in several countries, there is no reference of worldwide prevalence in infants.
      The aim of this meta-analysis is to estimate the prevalence of wheezing and
      recurrent wheezing in infants aged up to two years, and compare the prevalence
      across world regions. METHODS: Literature search was conducted in MEDLINE and
      SCOPUS databases, looking for observational studies published up to June 2016,
      including as keywords "prevalence" or "epidemiology" combined with "wheeze",
      "wheezing" or "asthma symptoms" and "infant" or "preschool". Fast*Pro software
      and random effects Bayesian model were used. Heterogeneity was estimated using I2
      statistic, and sensitivity analyses were performed. RESULTS: We identified 109
      studies after duplicates were removed. After exclusions, 14 studies were included
      in the meta-analysis. Prevalence of wheezing and recurrent wheezing were 36.06%
      (95% CI 35.17-36.96), and 17.41% (95% CI 16.74-18.09), respectively. In European
      countries, prevalence of wheezing was 30.68% (95% CI 28.97-32.45), and 12.35%
      (95% CI 11.27-13.47) for recurrent wheezing. Prevalence of wheezing and recurrent
      wheezing in Latin America were higher, 40.55% (95% CI 39.40-41.71), and 19.27%
      (95% CI 18.44-20.11), respectively. In Africa, prevalence of wheezing was 15.97%
      (95% CI 14.05-18.00). Low or no heterogeneity was found in all cases.
      CONCLUSIONS: More than one third of infants suffer from wheezing and almost one
      fifth from recurrent wheezing, being these illnesses especially prevalent in
      Latin American countries, pointing out an important public health problem.

PMID- 27865540
TI  - Cofactors and comorbidities in patients with aspirin/NSAID hypersensitivity.
AB  - Hypersensitivity reactions to aspirin and other NSAIDs occur in individuals
      genetically predisposed and exhibit different clinical manifestations, especially
      respiratory, cutaneous, and generalised. Five different phenotypes define
      distinct clinical pictures: aspirin-exacerbated respiratory disease,
      aspirin/NSAID cutaneous disease, NSAID-induced urticaria, angio-oedema and
      anaphylaxis, single NSAID reactions, and delayed reactions. They are observed
      more frequently in middle-aged women, and in atopic individuals. While ASA/NSAID
      hypersensitivity shares comorbidities with asthma, chronic rhinosinusitis, nasal
      polyposis, chronic urticaria and angio-oedema, ASA and other NSAIDs can also be
      cofactors for other clinically relevant conditions, especially food-dependent
      exercise-induced anaphylaxis, angio-oedema induced by angiotensin-converting
      enzyme inhibitors, and oral mite anaphylaxis. Awareness on these relationships is
      required for the correct diagnosis, classification, and treatment of affected
      patients.

PMID- 27865541
TI  - Editorial Comment.

PMID- 27865542
TI  - High-capacity hollow porous dummy molecular imprinted polymers using ionic liquid
      as functional monomer for selective recognition of salicylic acid.
AB  - The existence of strong intramolecular hydrogen bond in salicylic acid (SA)
      weakens its intermolecular hydrogen bonding with functional monomer, then it is a
      challenge work to fabricate molecularly imprinted polymers (MIPs) for SA
      recognition with high capacity and good selectivity. Here, hollow porous dummy
      MIPs (HPDMIPs) were prepared using benzoic acid (BA) as dummy template, ionic
      liquid (i.e. 1-vinyl-3-methylimidazolium chloride) as functional monomer, and MCM
      48 as sacrificial support. Factors that affected adsorption, such as type of
      template and porogen, mole ratio of template-functional monomer-cross-linker and
      type of binding solvent, were optimized in detail. Multiple strong interactions
      between SA and ionic liquid in HPDMIPs deduced higher binding capacity
      (29.75mg/g), imprinting factor (5.61) and selectivity than any previously
      reported MIPs by traditional or surface imprinting technology. The large surface
      area (543.9m2/g) with hollow porous structure resulted in faster kinetic binding
      (25min). The equilibrium data fitted well to Freundlich equation and the
      adsorption process could be described by pseudo-second order model. Finally,
      HPDMIPs were successfully applied to selectively extract and enrich SA from
      Actinidia chinensis with a relatively high recovery (84.6-94.5%).

PMID- 27865543
TI  - Patterns of care and survival outcomes in patients with pineal parenchymal tumor
      of intermediate differentiation: An individual patient data analysis.
AB  - BACKGROUND/PURPOSE: Pineal parenchymal tumor constitutes less than 1% of all CNS
      tumors. Pineal parenchymal tumor of intermediate differentiation is a rare tumor
      arising from the pineal parenchyma lying between the spectrum of Pineocytoma and
      Pineoblastoma. METHODS AND MATERIALS: We performed PubMed search with the
      following MesH terms: "pineal parenchymal tumor, pineal parenchymal tumor of
      intermediate differentiation, pineal parenchymal tumor of intermediate
      differentiation AND treatment, and pineal parenchymal tumor of intermediate
      differentiation AND survival" to find all possible publications pertaining to
      PPTID. Individual patient data on "age, gender, surgery, type of surgery,
      radiation and type of radiation, chemotherapy, recurrence, and survival" were
      tabulated. RESULTS: A total of 29 studies were found eligible with 127 patients.
      Median age was 33years (range: 4.5-75years). The male: female ratio was 1:1.6.
      Median MIB labeling index was 7 (range: 1-30). Adjuvant radiation was used in 46
      (36.2%) of the patients and chemotherapy was used in 29 (22.8%) patients. Of the
      patients who had recurrence 62.5% experienced spinal or leptomeningeal recurrence
      while 37.5% had local recurrence. The median progression free survival and
      overall survival were 5.17 and 14years respectively. Univariate analysis revealed
      female sex and the use of adjuvant radiation to be associated with better overall
      survival. CONCLUSION: PPTIDs are associated with a moderate outcome with a median
      progression free survival of 5.17years and median overall survival of 14years.
      Patients with a sub total resection should be treated with adjuvant radiotherapy
      as addition of radiation is associated with better survival outcomes.

PMID- 27865544
TI  - Central liver toxicity after SBRT: An expanded analysis and predictive nomogram.
AB  - PURPOSE: To further explore the correlation of central biliary tract (cHBT)
      radiation doses with hepatobiliary toxicity (HBT) after stereotactic body
      radiation therapy (SBRT) in a larger patient dataset. METHODS: We reviewed the
      treatment and outcomes of all patients who received SBRT for primary liver cancer
      (PLC) and metastatic liver tumors between July 2004 and November 2015 at our
      institution. The cHBT was defined as isotropic expansions (5, 10, 15, 20 and
      25mm) from the portal vein (PV). Doses were converted to biologically effective
      doses by using the standard linear quadratic model with alpha/beta of 10 (BED10).
      HBT was graded according to the Common Terminology Criteria for Adverse Events
      v4.03. RESULTS: Median follow-up was 13months. Out of the 130 patients with
      complete follow-up records analyzed, 60 (46.1%) had liver metastases, 40 (30.8%)
      had hepatocellular carcinoma (HCC), 26 (20%) had cholangiocarcinoma (CCA) and 4
      (3.1%) patients other PLC histologies. Thirty-three (25.4%) grade 2+ and 28
      (21.5%) grade 3+ HBT were observed. Grade 3+ HBT was seen in 13 patients (50%)
      with CCA, 7 patients (17.5%) with HCC and 7 (11.7%) patients with liver
      metastases. SBRT doses to the cHBT were highly associated with HBT, but only for
      PLC patients when analyzed by histological subtype. The 15mm expansion from the
      PV (cHBT15) proved to be an appropriate surrogate for the cHBT. The strongest
      cHBT15 dose predictors for G3+ HBT for PLC were the VBED1040?37cc (p<0.0001) and
      the VBED1030?45cc (p<0.0001). CONCLUSION: SBRT doses to the cHBT are associated
      with occurrence of HBT only in PLC patients. Limiting the dose to the cHBT to
      VBED1040<37cc and VBED1030<45cc when treating PLC patients with SBRT may reduce
      the risk of HBT.

PMID- 27865546
TI  - French consensus. Management of patients with hypersomnia: Which strategy?
AB  - Central hypersomnias principally involves type 1 narcolepsy (NT1), type 2
      narcolepsy (NT2) and idiopathic hypersomnia (IH). Despite great progress made in
      understanding the physiopathology of NT1 with low cerebrospinal fluid hypocretin
      1 levels, current treatment remains symptomatic. The same applies to NT2 and IH,
      for which the physiopathology is still largely unknown. Controlling excessive
      daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis
      and disturbed night-time sleep are key therapeutic targets in NT1. For IH and
      NT2, reducing EDS is the main objective. Based on European and American
      directives for the treatment of narcolepsy, we propose French recommendations for
      managing central hypersomnias as well as strategies in the case of drug
      resistance. Stimulating treatments target EDS, and Modafinil is the first-line
      treatment. Other stimulants such as methylphenidate, pitolisant, and
      exceptionally dextro-amphetamine can be prescribed. Selective serotonin and
      noradrenaline reuptake inhibitor antidepressants are effective for the management
      of cataplexy in NT1. Sodium oxybate is an effective treatment for several
      symptoms, including EDS, cataplexy and disturbed night-time sleep. Treatment of
      central hypersomnia must also take into consideration frequent cardiovascular,
      metabolic and psychiatric comorbidities, particularly in NT1. New therapies are
      currently under study with the development of new stimulants and anti
      cataplectics. The next few years will see innovative emerging therapies, based on
      a physiopathological approach, aiming to restore hypocretinergic transmission or
      to interrupt the autoimmune processes causing the loss of hypocretin neurons.

PMID- 27865545
TI  - Anti-CGRP antibodies block CGRP-induced diarrhea in mice.
AB  - The multifunctional neuropeptide calcitonin gene-related peptide (CGRP) and its
      receptor are expressed throughout the gastrointestinal tract. Previous studies
      have shown that CGRP has roles in intestinal motility, water secretion, and
      inflammation. Furthermore, animal studies have demonstrated CGRP involvement in
      diarrhea secondary to C. difficile and food allergies. Diarrhea thus provides a
      convenient bioassay of CGRP activity in the GI system. In this proof of principle
      study, we report that prophylactic administration of an anti-CGRP antibody is
      able to block CGRP-induced diarrhea in mice. As a control, the CGRP-receptor
      antagonist olcegepant also attenuated the diarrhea response to CGRP. This
      preclinical study indicates that anti-CGRP antibodies may provide a new
      preventative therapy for gastrointestinal disorders involving CGRP.

PMID- 27865547
TI  - Isolated cortical vein thrombosis associated with clinically amyopathic
      dermatomyositis.

PMID- 27865549
TI  - Anaemia and fever in Kidney transplant. The role of human parvovirus B19.
AB  - Infections remain an issue of particular relevance in renal transplant patients,
      particularly viral infections. Human parvovirus B19 infection causes severe
      refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is
      recognized by analysing blood polymerase chain reaction (PCR) and by the
      discovery of typical giant proerythroblasts in the bone marrow. We report the
      case of a 65 year-old man with a history of deceased donor renal transplant in
      September 2014. At 38 days after the transplant, the patient presented
      progressive anaemia that was resistant to erythropoiesis-stimulating agents. At
      64 days after transplant, hyperthermia occurred with progressive deterioration of
      the patient's general condition. The viral serology and the first blood PCR for
      human parvovirus B19 were both negative. At 4 months and 19 days after, a bone
      marrow biopsy was conducted, showing giant erythroblasts with nuclear viral
      inclusions that were compatible with parvovirus; a PCR in the tissue confirmed
      the diagnosis. A second blood PCR was positive for parvovirus. After treatment
      with intravenous immunoglobulin and the temporary discontinuation of
      mycophenolate mofetil, a complete remission of the disease occurred, although the
      blood PCR for parvovirus B19 remained positive, so monitoring is necessary for
      future likely recurrence.

PMID- 27865548
TI  - Household and caregiver characteristics and behaviours as predictors of unsafe
      exposure of children to paraffin appliances.
AB  - This study examines adult safety knowledge and practices regarding the use of
      paraffin cooking appliances. The use of these is common in South Africa with
      injury risks that are poorly understood. This cross-sectional study was in an
      informal settlement in Johannesburg, South Africa, where children were reportedly
      at high risk for burns. This study sought to clarify relationships between key
      risks and developed individual and composite variables from theoretical
      constructs and operational definitions of risks for burns. Risks included Child
      Use of Paraffin Appliances, Child Proximity to Cooking, Risky Stove Use,
      Caregiver's Burn Treatment Knowledge, Children Locked in House, Children Alone in
      House. Number of children remains as in proof as this was not a composite scale.
      Child Proximity to Cooking was associated with more children in the home.
      Households where children were in greater proximity to cooking were 6 times more
      likely to be left alone at home, with caregivers with no education over 100 times
      more likely to lock their children at home. Children locked in were often from
      homes where caregivers used appliances unsafely. In settings with hazardous
      energy use, compressed household configurations, and families with multiple
      children, Risky Stove Use and the practice of locking children in the home may be
      catastrophic.

PMID- 27865550
TI  - The star fruit as a cause of acute kidney injury.

PMID- 27865551
TI  - Objective Voice Analysis of Pediatric Cochlear Implant Recipients and Comparison
      With Hearing Aids Users and Hearing Controls.
AB  - OBJECTIVES: Phonation is influenced by hearing as a feedback mechanism. The
      purpose of the present study was to compare selected acoustic parameters in
      children using cochlear implants (CIs), those using hearing aids (HA), and their
      normal-hearing (NH) peers. METHODS: The participants were 15 children using CI
      (mean age: 72 months), 15 children using HA (mean age: 74 months), and 15 NH
      children (mean age: 77 months). The vowel /a/ was produced to measure
      perturbation and mean fundamental frequency. The six Persian vowels in /CbVCd/
      were obtained to extract vowel duration. Data were analyzed by one-way analysis
      of variance. RESULTS: Results revealed a statistically significant difference
      between the NH group and the HA group regarding fundamental frequency (F2,51 =
      3.443, P < 0.05), jitter local (F2,51 = 1.629, P < 0.05), jitter local absolute
      (F2,51 = 6.519, P < 0.001), jitter rap (F2,51 = 7.151, P < 0.001), jitter ppq5
      (F2,51 = 5.894, P < 0.001), shimmer local (%) (F2,51 = 8.070, P < 0.001), shimmer
      local (dB) (F2,51 = 3.884, P < 0.05), shimmer apq3 (F2,51 = 4.926, P < 0.05),
      shimmer apq5 (F2,51 = 8.442, P < 0.001), and harmonic-to-noise ratio (F2,51 =
      4.117, P < 0.001). The mean values of the duration of all six vowels were
      significantly greater in children with CI and HA than in NH children (P < 0.001).
      CONCLUSION: It seems that after 8 months of using CI, auditory control of voice
      production would be enabled. Furthermore, children with hearing impairment
      potentially regard vowel sound duration as a distinguishing feature, whereas in
      NH speakers, the duration has the least effect in vowel identification.

PMID- 27865553
TI  - The need for personalized resuscitation guidelines in children with congenital
      heart disease.

PMID- 27865552
TI  - Relationship between Voice Complaints and Subjective and Objective Measures of
      Vocal Function in Iranian Female Teachers.
AB  - OBJECTIVES: Teachers are at high risk of developing voice problems because of the
      excessive vocal demands necessitated by their profession. Teachers' self
      assessment of vocal complaints, combined with subjective and objective measures
      of voice, may enable better therapeutic decision-making. This investigation
      compared audio-perceptual assessment and acoustic variables in teachers with and
      without voice complaints. METHODS: Ninety-nine teachers completed this cross
      sectional study and were assigned to one of two groups: those "with voice
      complaint (VC)" and those "without voice complaint (W-VC)." Voice samples were
      collected during reading, counting, and vowel prolongation tasks. Teachers were
      also asked to document any voice symptoms they experienced. Voice samples were
      analyzed using Dr. Speech program (4th version; Tiger Ltd., USA), and labeled
      "normal" or "abnormal" according to the "grade" dimension "G" from GRBAS scale.
      RESULTS: Twenty-one teachers were assigned to the VC group based on self
      assessment data. There were statistically significant differences between the two
      groups with regard to self-reported voice symptoms of hoarseness, breathiness,
      pitch breaks, and vocal fatigue (P < 0.05). Fourteen participants in the VC group
      and 40 from the W-VC group were determined to demonstrate "abnormal" vocal
      quality on perceptual assessment. Only harmonic-to-noise ratio was significantly
      higher for the W-VC group (ES = 0.55). CONCLUSION: Teachers with and without
      voice complaints differed in the incidence, but not type of voice symptoms.
      Teachers' voice complaints did not correspond to perceptual and acoustic
      measures. This suggests a potential unmet need for teachers to receive further
      education on voice disorders.

PMID- 27865554
TI  - Just because you can, doesn't mean you should: The flipside of technical
      feasibility.

PMID- 27865555
TI  - Calpain inhibitors: The aspirin of the 21st century?

PMID- 27865557
TI  - Hypoperfusion of the thalamus is associated with disability in relapsing
      remitting multiple sclerosis.
AB  - BACKGROUND: While gray matter (GM) perfusion abnormalities have been evidenced in
      multiple sclerosis (MS) patients, the relationships with disability still remain
      unclear. Considering that atrophy is known to impact on perfusion, we aimed to
      assess perfusion abnormalities in GM of MS patients, outside atrophic regions and
      investigate relationships with disability. METHODS: Brain perfusion of 23
      relapsing remitting MS patients and 16 matched healthy subjects were assessed at
      3T using the pseudo-continuous arterial spin labeling magnetic resonance imaging
      technique. In order to locate potential GM perfusion abnormalities in regions
      spared by atrophy, we combined voxelwise comparisons of GM cerebral blood flow
      (CBF) maps (cortex and deep GM) (P<0.005, FWE-corrected) and voxel-based
      morphometry analysis (P<0.005, FDR-corrected) to exclude atrophic regions.
      Disability was assessed using the Expanded Disability Status Scale (EDSS) and the
      Multiple Sclerosis Functional Composite score (MSFC). RESULTS: In patients,
      significant GM hypoperfusion outside atrophic regions was depicted only in
      bilateral thalami. No other cluster was found to be hypoperfused compared to
      controls. Perfusion of thalami was correlated to MSFC (P=0.011, rho=0.523). A
      trend of correlation was found between perfusion of thalami and EDSS (P=0.061,
      rho=-0.396). CONCLUSION: In relapsing remitting MS, perfusion abnormalities in
      thalamic regions contribute to disability. These findings suggest that functional
      impairments of thalami, representing a major brain hub, may disturb various
      cerebral functions even before structural damage.

PMID- 27865556
TI  - Trans-crocetin improves amyloid-beta degradation in monocytes from Alzheimer's
      Disease patients.
AB  - Herbal medicines have been recently employed in research and clinical studies for
      the potential treatment of behavioral and psychological symptoms associated with
      Alzheimer's Disease (AD) and other types of dementia. The present study
      investigates the effect of trans-crocetin, an active constituent of Crocus
      sativus L., to restore in vitro the reduced ability of AD patients' monocytes to
      degrade amyloid-beta(1-42) (Abeta42). CD14+ monocytes from 22 sporadic AD
      patients with moderate cognitive impairment were isolated; then, the role of
      trans-crocetin, purified from saffron extracts, was evaluated in terms of Abeta42
      degradation rate through flow cytometry, as well as expression of cathepsin B by
      Western blotting. We observed that low micromolar doses of trans-crocetin
      enhanced Abeta42 degradation in AD monocytes through the upregulation of the
      lysosomal protease cathepsin B. CA074Me, a potent and selective cathepsin B
      inhibitor, counteracted such trans-crocetin-induced effect. These data suggest
      that the carotenoid trans-crocetin improves in vitro the clearance of Abeta42
      through the involvement of cathepsin B, and this could be of value in developing
      a new anti-amyloid strategy in AD.

PMID- 27865558
TI  - Ligand binding to Ryanodine Receptors revealed through cryo-electron microscopy.

PMID- 27865560
TI  - Reply to "statins and non-alcoholic steatohepatitis".

PMID- 27865561
TI  - The cost effectiveness of vacuum-assisted versus core-needle versus surgical
      biopsy of breast lesions.
AB  - OBJECTIVES: To determine the cost effectiveness of breast biopsy by 9G vacuum
      assisted guided by vertical stereotaxy or ultrasonography in comparison with
      breast biopsy by 14G core-needle biopsy and surgical biopsy. MATERIAL AND
      METHODS: We analyzed a total of 997 biopsies (181 vacuum-assisted, 626 core, and
      190 surgical biopsies). We calculated the total costs (indirect and direct) of
      the three types of biopsy. We did not calculate intangible costs. We measured the
      percentage of correct diagnoses obtained with each technique. To identify the
      most cost-effective option, we calculated the mean ratios for the three types of
      biopsies. RESULTS: Total costs were ?225.09 for core biopsy, ?638.90 for vacuum
      assisted biopsy, and ?1780.01 for surgical biopsy. The overall percentage of
      correct diagnoses was 91.81% for core biopsy, 94.03% for vacuum-assisted biopsy,
      and 100% for surgical biopsy; however, these differences did not reach
      statistical significance (p=0.3485). For microcalcifications, the percentage of
      correct diagnoses was 50% for core biopsy and 96.77% for vacuum-assisted biopsy
      (p<0.0001). For nodules, there were no significant differences among techniques.
      The mean cost-effectiveness ratio considering all lesions was 2.45 for core
      biopsy, 6.79 for vacuum-assisted biopsy, and 17.80 for surgical biopsy.
      CONCLUSION: Core biopsy was the dominant option for the diagnosis of suspicious
      breast lesions in general. However, in cases with microcalcifications, the low
      percentage of correct diagnoses achieved by core biopsy (50%) advises against its
      use in this context, where vacuum-assisted biopsy would be the technique of
      choice because it is more cost-effective than surgical biopsy, the other
      technique indicated for biopsying microcalcifications.

PMID- 27865562
TI  - Photo- and thermo-responsive multicompartment hydrogels for synergistic delivery
      of gemcitabine and doxorubicin.
AB  - Hydrogels have found promising applications in drug delivery due to their
      biocompatibility, high drug loading capability, and tunable release profiles.
      However, hydrogel-based carriers are primarily employed for delivering
      hydrophilic payloads while hydrophobic drugs cannot be efficiently delivered due
      to the lack of hydrophobic domains within conventional hydrogel matrices. Herein,
      we report that thermo- and photo-responsive hydrogels could be constructed from
      amphiphilic triblock copolymers, poly(N-isopropylacrylamide)-b-poly(4
      acryloylmorpholine)-b-poly(2-((((2-nitrobenzyl)oxy)carbonyl) amino)ethyl
      methacrylate) (PNIPAM-b-PNAM-b-PNBOC), and the resulting hydrogels could be
      further engineered a new carrier for both hydrophilic gemcitabine (GCT) and
      hydrophobic doxorubicin (DOX). PNIPAM-b-PNAM-b-PNBOC triblock copolymers were
      first self-assembled into micelles with hydrophobic photosensitive PNBOC cores,
      hydrophilic PNAM inner shells, and thermoresponsive PNIPAM coronas below the
      lower critical solution temperature (LCST), while hydrogels of physically cross
      linked micellar nanoparticles were achieved at elevated polymer concentrations
      and high temperatures above the critical gelation temperature (CGT). Rheological
      experiments revealed that the CGT was highly dependent on polymer compositions
      and concentrations, that is, a longer hydrophobic PNBOC block or a higher polymer
      concentration led to a decreased CGT. However, the CGT prior to UV irradiation
      (CGT0) could be drastically elevated after UV irradiation (CGTUV) as a result of
      UV irradiation-induced concurrently cross-linking and hydrophobic-to-hydrophilic
      transition within PNBOC cores. As such, gel-to-sol transition could be
      accomplished by either temperature decrease or exposure to UV irradiation at a
      fixed temperature lower than the CGTUV. Note that both GCT and DOX could be
      simultaneously encapsulated into the hydrogels due to the coexistence of
      extramicellar aqueous phase and hydrophobic micellar cores. Intriguingly, the
      subsequent co-release of GCT and DOX could be regulated by taking advantage of
      either temperature or UV irradiation-mediated gel-to-sol transitions.

PMID- 27865564
TI  - Pneumococcal pep27 mutant immunization stimulates cytokine secretion and confers
      long-term immunity with a wide range of protection, including against non
      typeable strains.
AB  - Streptococcus pneumoniae is comprised of more than 90 serotypes and is the major
      causative agent of pneumonia, which results in over 1million deaths worldwide
      every year. Currently available injectable vaccines can protect against only 13
      23 serotypes, and result in decrease of colonization against vaccine serotypes.
      However, they are neither effective for inhibition of non-vaccine serotypes
      colonization nor inhibition against initial colonization in the nasopharynx
      against various serotypes. Thus, development of a vaccine conveying broader
      protection at the colonization stage is required. This study examined whether the
      Deltapep27 mutant could provide protection at the nasopharynx against a broad
      range of serotypes. Deltapep27 immunization stimulated secretion of IL-4, IL-10,
      TNF-alpha, INF-gamma and IL-17, and significantly increased secretory-IgA levels
      in bronchoalveolar lavage fluid. Colonization and opsonophagocytosis assays
      demonstrated that Deltapep27 immunization could protect against many heterologous
      infections, including non-typeable strains, at the nasopharynx, and prompted
      efficient killing of heterologous strains, suggesting that Deltapep27
      immunization provides a wide range of cross-protection. Furthermore, Deltapep27
      immunization significantly increased both the survival rate and the level of IgG
      3months post-immunization, demonstrating long-lasting immunity. Thus, Deltapep27
      could serve as a highly feasible mucosal vaccine once it is further developed
      into a non-transformable strain.

PMID- 27865563
TI  - Sonic Hedgehog Signaling and Hippocampal Neuroplasticity.
AB  - Sonic hedgehog (Shh) is a secreted protein that controls the patterning of neural
      progenitor cells, and their neuronal and glial progeny, during development.
      Emerging findings suggest that Shh also has important roles in the formation and
      plasticity of neuronal circuits in the hippocampus, a brain region of fundamental
      importance in learning and memory. Shh mediates activity-dependent and injury
      induced hippocampal neurogenesis. Activation of Shh receptors in the dendrites of
      hippocampal neurons engages a trans-neuronal signaling pathway that accelerates
      axon outgrowth and enhances glutamate release from presynaptic terminals.
      Impaired Shh signaling may contribute to the pathogenesis of several
      developmental and adult-onset neurological disorders that affect the hippocampus,
      suggesting a potential for therapeutic interventions that target Shh pathways.

PMID- 27865565
TI  - [Ankle-brachial index screening for peripheral artery disease in high
      cardiovascular risk patients. Prospective observational study of 370 asymptomatic
      patients at high cardiovascular risk].
AB  - INTRODUCTION: Peripheral arterial disease is a marker of systemic
      atherosclerosis; it is associated with a high risk of cardiovascular disease. The
      aim of our study was to assess the prevalence of peripheral arterial disease by
      measuring the ankle-brachial pressure index in patients at high cardiovascular
      risk and to study the risk factors associated with this disease. METHODOLOGY:
      This was a descriptive and analytic cross-sectional study which focused on 370
      patients seen at the medical consultation for atherosclerosis prevention. The
      ankle-brachial index was measured with a portable Doppler (BIDOP 3) using 4 and
      8Hz dual frequency probes. The standards were: normal ankle-brachial index 0.9 to
      1.3; peripheral artery obstructive disease ankle-brachial index less than 0.9;
      poorly compressible artery (medial arterial calcification) ankle-brachial index
      greater than 1.3. Cardiovascular risk factors were also studied. RESULTS: Three
      hundred and seventy subjects (mean age 65.5+/-8.7years) were screened
      Cardiovascular risk factors were: sedentary lifestyle (91.5 %), hypertension
      (68.1 %), elevated LDL-cholesterolemia (36.3 %), diabetes (48.3 %) and tobacco
      smoking (33.8 %). The prevalence of peripheral artery disease was 32.4 % of which
      77.5 % were asymptomatic. We found a significant correlation with smoking,
      diabetes, dyslipidemia and the presence of coronary artery disease or vascular
      cerebral disease. Screening for peripheral arterial disease (PAD) with the ankle
      brachial index has increased the percentage of polyvascular patients from 6.2 to
      29 %. Factors independently associated with PAD were advanced age, presence of
      cardiovascular disease, smoking and glycated hemoglobin. CONCLUSION: PAD is a
      common condition in people at high cardiovascular risk, the frequency of
      asymptomatic forms justifies the screening with pocket Doppler which is a simple,
      inexpensive and effective test to assess the overall cardiovascular risk.

PMID- 27865567
TI  - Preconceptional and perinatal exposure to traffic-related air pollution and
      eczema in preschool children.
AB  - BACKGROUND: Evidence linking prenatal exposure to outdoor air pollution with
      eczema in early childhood is scare, and the role of components of air pollution
      and exposure timing remains unclear. OBJECTIVES: We investigated the association
      between exposure to air pollution during preconceptional and perinatal period and
      the risk of eczema in preschool children. METHODS: We conducted a prospective
      cohort study of 2598 children aged 3-6 years in Changsha, China. The prevalence
      of eczema was assessed by a standardized health questionnaire administered by the
      parents. Individual exposures to nitrogen dioxide (NO2), sulfur dioxide (SO2) and
      particulate matter with an aerodynamic diameter<=10MUm (PM10) during the 4th-6th
      and 1st-3rd month before pregnancy, entire pregnancy, and three trimesters were
      estimated by an inverse distance weighted (IDW) method based on concentrations
      measured at monitoring stations. Association between childhood eczema and
      exposure to air pollution was examined by logistic regression models in terms of
      odds ratio (OR) and 95% confidence interval (CI) for an interquartile range (IQR)
      increase in exposure. RESULTS: Life-time prevalence of eczema in preschool
      children in Changsha was 28.6%. Childhood eczema was associated with traffic
      related air pollutant NO2 during 3 months before pregnancy and entire pregnancy
      with adjusted ORs=1.19 (95% CI: 1.04-1.37) and 1.21 (95% CI: 1.03-1.42)
      respectively. The highest risk of eczema was observed for the 1st trimester
      exposure to NO2 [OR=1.26 (95% CI: 1.09-1.46)]. However, no association was
      detected for SO2 and PM10 exposure during any window. High-level exposure to NO2
      during the whole time period significantly increased the effect of NO2 in all
      windows on eczema risk as compared with low-level exposure. Sensitivity analysis
      indicated that the association between both preconceptional and perinatal
      exposure to NO2 and childhood eczema was consistent and robust, and this
      association was modified by some personal, parental hereditary and indoor
      environmental factors. CONCLUSION: Our findings support the hypothesis that early
      childhood eczema is associated with exposure to traffic-related air pollutant
      during both preconceptional and perinatal period, especially at a high level of
      exposure.

PMID- 27865566
TI  - Phosphorus Additives and Albuminuria in Early Stages of CKD: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Little is known about the effects of phosphorus additives on patients
      with kidney disease. STUDY DESIGN: Randomized, double-blind, crossover trial.
      SETTING & PARTICIPANTS: 31 adults with early stages of presumed chronic kidney
      disease (estimated glomerular filtration rate >= 45mL/min/1.73m2; urine albumin
      creatinine ratio sex-specific cutoff points: men >= 17mg/g, women >= 25mg/g).
      INTERVENTION: Higher versus lower phosphorus intake for 3 weeks. Higher
      phosphorus intake was achieved by the addition of commercially available diet
      beverages and breakfast bars to diet. OUTCOMES: Change in 24-hour urine albumin
      excretion and plasma fibroblast growth factor 23 level. MEASUREMENTS: Two 24-hour
      urine collections and a single fasting blood draw at the end of each period.
      RESULTS: Mean baseline values for phosphorus intake, 24-hour urine phosphorus
      excretion, and estimated glomerular filtration rate were 1,113+/-549 (SD) mg/d,
      688+/-300mg/d, and 74.6+/-22.0mL/min/1.73m2. Median urine albumin excretion of
      82.7 (IQR, 39.6-174.1) mg/d. Although phosphorus intake from study products
      increased by 993mg/d (P<0.001) during the higher compared to lower phosphorus
      additive period, background phosphorus intake decreased by 151mg/d (P=0.004).
      Higher phosphorus additive consumption increased 24-hour urine phosphorus
      excretion by 505 (95% CI, 381 to 629) mg/d (P<0.001), but did not significantly
      increase albuminuria (higher vs lower: 14.3%; 95% CI, -2.5% to 34.0%; P=0.1) or
      fibroblast growth factor 23 level (higher vs lower: 3.4%; 95% CI, -5.9% to 13.6%;
      P=0.4). LIMITATIONS: Small sample size, short duration of intervention, changes
      in background diet during the intervention. CONCLUSIONS: A 3-week consumption of
      higher phosphorus food additives did not significantly increase albuminuria.
      Further studies are needed to confirm these results.

PMID- 27865568
TI  - Home Discharge After Primary Elective Total Joint Arthroplasty: Postdischarge
      Complication Timing and Risk Factor Analysis.
AB  - BACKGROUND: Bundled payment programs for primary total joint arthroplasty (TJA)
      have identified reducing nonhome discharge as a major area of cost savings.
      Health care providers must therefore identify, risk stratify, and appropriately
      care for home-discharged TJA patients. This study aimed to analyze risk factors
      and timing of postdischarge complications among home-discharged primary total hip
      arthroplasty (THA) and total knee arthroplasty (TKA) patients and risk stratify
      them to identify those who would benefit from higher level care. METHODS:
      Patients discharged home after elective primary THA/TKA from 2011 to 2014 were
      identified in the National Surgical Quality Improvement Program database.
      Bivariate and multivariate analyses were performed using perioperative variables.
      RESULTS: A total of 50,376 and 71,293 home-discharged THA and TKA patients were
      included for analysis, of which, 1575 THA (3.1%) and 2490 TKA (3.5%) patients
      suffered postdischarge severe complications or unplanned readmissions. These
      patients were older, smokers, obese, and functionally dependent (P < .001 for
      all). In multivariate analysis, severe adverse event predischarge, age, male
      gender, functional status, and 10 other variables were all associated with >=1.22
      odds of postdischarge severe adverse event or readmission (P < .05). THA and TKA
      patients with 2, 3, or >=4 risk factors had 1.43-5.06 times odds of complications
      within 14 days post discharge and 1.41-3.68 times odds of complications beyond 14
      days compared to those with 0 risk factors (P < .001 for all). CONCLUSION: Risk
      factors can be used to predict which home-discharged TJA patients are at greatest
      risk of postdischarge complications. Given that this is a growing population, we
      recommend the development of formal risk-stratification protocols for home
      discharged TJA patients.

PMID- 27865569
TI  - Response to Letter to the Editor on 'Tibiofemoral Dislocation After Total Knee
      Arthroplasty'.

PMID- 27865570
TI  - Letter to the Editor on 'Tibiofemoral Dislocation After Total Knee Arthroplasty'.

PMID- 27865571
TI  - The authors respond: methodological issues in studying shock indices.

PMID- 27865572
TI  - Salmonella colitis as an unusual cause of elevated serum lipase.
AB  - Authors and clinicians advocate lipase as the preferred serological test for the
      diagnosis for acute pancreatitis. While acute pancreatitis is among the
      differential diagnosis for elevated lipase levels, several other causes of
      elevated lipase levels have been identified including several reports Salmonella
      species as a causative agent. There also have been retrospective studies that
      have reported clinical pancreatitis associated with Salmonella infection. These
      studies concluded that clinical pancreatitis should be considered as a
      complication of Salmonella infections. However, Salmonella infections may induce
      elevated pancreatic enzyme levels without clinical pancreatitis or morphological
      pancreatic abnormalities through a variety of proposed mechanisms. The following
      is a case that describes a patient who developed Salmonella colitis and
      demonstrated elevated serum lipase levels without clinical pancreatitis.

PMID- 27865573
TI  - Polyarteritis nodosa presenting as bilateral Wunderlich syndrome: Rare cause of
      flank pain in a young woman.

PMID- 27865574
TI  - Comparison of blind intubation through the I-gel and the Air-QTM by novice
      physicians during cardiopulmonary resuscitation: A randomized, crossover, manikin
      trial.

PMID- 27865575
TI  - Pathophysiology of Severe diabetic ketoacidosis presenting with negative serum
      ketones.

PMID- 27865576
TI  - Embolization of Congenital Renal Arteriovenous Malformations Using Ethanol and
      Coil Depending on Angiographic Types.
AB  - PURPOSE: To evaluate effectiveness and safety of embolization of congenital renal
      arteriovenous malformations (AVMs) using ethanol and/or coil according to
      angiographic type. MATERIALS AND METHODS: Between August 2010 and October 2015,
      11 patients (13 sessions; 10 women and 1 man; mean age, 50.8 y) with congenital
      renal AVMs were treated using ethanol and/or coils via 2 approaches
      (transarterial access or direct puncture). Demographics, clinical findings,
      diagnostic modalities, angiographic types, technical and clinical success rates,
      and complications were reviewed. Renal AVMs were classified into 3 angiographic
      types, and treatment was based on this classification. RESULTS: Technical success
      rate was 91% (10/11), and clinical success rate was 100% (11/11). Of patients, 7
      had type III AVMs, 3 had type I AVMs, and 1 had type II AVM. Embolic agents were
      ethanol in 5 patients, coils with ethanol in 3 patients, and coils in 3 patients.
      Of the 8 patients treated with ethanol, 6 had infarcted renal areas of 3.5%-30%
      (mean, 14.6%). After a mean follow-up period of 16.3 months, there was no
      evidence of recurrent AVMs on imaging or laboratory studies. CONCLUSIONS:
      Embolization of congenital renal AVMs via transarterial or direct percutaneous
      approaches using ethanol and/or coils based on a simple angiographic
      classification was safe and effective and elicited good outcomes. Most of the
      patients with congenital renal AVMs were women.

PMID- 27865577
TI  - Influence of Statin Therapy on Aneurysm Sac Regression after Endovascular Aortic
      Repair.
AB  - PURPOSE: To determine whether statin therapy is associated with abdominal aortic
      aneurysm (AAA) sac regression after endovascular aneurysm repair (EVAR).
      MATERIALS AND METHODS: A total of 109 patients treated with EVAR were
      retrospectively analyzed (no-statin group, n = 45; statin group, n = 64). The
      primary endpoint was the incidence of AAA sac regression. To investigate
      independent predictors of AAA sac regression, regression analysis was performed.
      The mean age was 74 years (range, 55-90 y), and 87.2% of patients were men.
      RESULTS: The no-statin group had higher rates of AAA sac regression than the
      statin group at 1 year (no-statin group, 66.7%; statin group, 45.3%; P = .028).
      The incidence of AAA sac regression increased over time in the statin group, and
      no statistical difference was seen between the two groups at 2 years (no-statin
      group, 66.7%; statin group, 57.8%; P = .350). The difference between the changes
      in maximum AAA diameter was significant between groups at 1 year (no-statin group
      vs statin group, -4.9 mm +/- 5.9; P = .041), but the difference did not reach
      statistical significance at 2 years (no-statin group, -10.0 mm +/- 10.1; statin
      group, -8.0 mm +/- 9.6; P = .306). Statin therapy was not associated with AAA sac
      regression on univariate (odds ratio [OR], 0.685; 95% confidence interval [CI],
      0.310-1.516; P = .351) and multivariate analyses (OR, 0.617; 95% CI, 0.215-1.772;
      P = .369). CONCLUSIONS: Statin therapy had no effect on AAA sac regression at 2
      years. There is insufficient evidence to recommend statin therapy for AAA sac
      regression.

PMID- 27865578
TI  - Comparison of the Carlsson-Dent and GERD-Q questionnaires for gastroesophageal
      reflux disease symptom detection in a general population.
AB  - INTRODUCTION: Gastroesophageal reflux disease (GERD) is an extremely common
      pathology in the general population and one of the main reasons for consultation
      in gastroenterology. There are different instruments for detecting its symptoms,
      but few studies comparing one tool with another have been conducted in Mexico.
      AIMS: To compare the effectiveness of the Carlsson-Dent questionnaire (CDQ) and
      the GERD-Q questionnaire (GQQ) in detecting GERD symptoms in a general
      population. MATERIALS AND METHODS: A prospective, descriptive, cross-sectional
      study was conducted on 220 individuals in an open population within the time
      frame of May-June 2015. The subjects were evaluated through the self-assessment
      CDQ and GQQ. The positive scores from the CDQ (>= 4) were compared with those of
      the GQQ (>= 8), to determine which of the two instruments more easily detected
      patients with GERD symptoms. RESULTS: Fifty-seven percent of the patients were
      men and the mean patient age was 38.1 years. Fifty percent of the subjects
      presented with GERD symptoms with a positive score in at least one questionnaire;
      45% had positive CDQ results and 23% had positive GQQ results. Fifty-seven
      percent of the patients with a positive CDQ score presented with
      overweight/obesity, as did 72% of the patients with a positive GQQ result.
      Finally, 20% of the individuals had positive results for reflux symptoms in both
      questionnaires. CONCLUSIONS: There was a prevalence of GERD symptoms in 50% of
      the individuals studied from a general population. The GQQ detected a greater
      number of GERD symptoms in patients that presented with overweight/obesity and
      the CDQ was considered easier for patients to understand and answer. It is
      striking that there was only 20% agreement between the two questionnaires,
      suggesting that they may be useful for identifying GERD symptoms in different
      populations.

PMID- 27865579
TI  - Impact of childhood psoriasis on parents of affected children.
AB  - BACKGROUND: Childhood diseases, such as atopic dermatitis, have a negative impact
      on quality of life (QoL) of parents. How pediatric psoriasis affects a parent's
      QoL is unknown. OBJECTIVE: To explore the impact of childhood psoriasis on the
      lives of the parents. METHODS: Semistructured interviews were conducted with 31
      parents of children with psoriasis. Narrative data were analyzed and a conceptual
      framework of the effects of childhood psoriasis on parents was developed.
      RESULTS: All parents reported that their child's psoriasis caused a substantial,
      negative impact on their own QoL. A conceptual framework showed a negative impact
      on health and self-care, emotional well-being, family and social function,
      personal well-being, and life pursuits. Emotional well-being was the most
      affected domain. LIMITATIONS: It was not possible to correlate psoriasis severity
      with parental QoL. CONCLUSION: Childhood psoriasis alters the QoL of parents in
      multiple ways. Information from this study can be used to develop a QoL
      instrument to explore treatment and support strategies for families affected by
      pediatric psoriasis.

PMID- 27865580
TI  - The role of dual-energy computed tomography in the assessment of pulmonary
      function.
AB  - The assessment of pulmonary function, including ventilation and perfusion status,
      is important in addition to the evaluation of structural changes of the lung
      parenchyma in various pulmonary diseases. The dual-energy computed tomography
      (DECT) technique can provide the pulmonary functional information and high
      resolution anatomic information simultaneously. The application of DECT for the
      evaluation of pulmonary function has been investigated in various pulmonary
      diseases, such as pulmonary embolism, asthma and chronic obstructive lung disease
      and so on. In this review article, we will present principles and technical
      aspects of DECT, along with clinical applications for the assessment pulmonary
      function in various lung diseases.

PMID- 27865582
TI  - Orientation of the electrical heart axis in mid-term pregnancy.

PMID- 27865583
TI  - Huge Nabothian cyst causing Hematometra (case report).

PMID- 27865584
TI  - Cooperation and deception in primates.
AB  - Though competition and cooperation are often considered opposing forces in an
      arms race driving natural selection, many animals, including humans, cooperate in
      order to mitigate competition with others. Understanding others' psychological
      states, such as seeing and knowing, others' goals and intentions, and
      coordinating actions are all important for complex cooperation-as well as for
      predicting behavior in order to take advantage of others through tactical
      deception, a form of competition. We outline evidence of primates' understanding
      of how others perceive the world, and then consider how the evidence from both
      deception and cooperation fits this framework to give us a more complete
      understanding of the evolution of complex social cognition in primates. In
      experimental food competitions, primates flexibly manipulate group-mates'
      behavior to tactically deceive them. Deception can infiltrate cooperative
      interactions, such as when one takes an unfair share of meat after a coordinated
      hunt. In order to counter competition of this sort, primates maintain cooperation
      through partner choice, partner control, and third party punishment. Yet humans
      appear to stand alone in their ability to understand others' beliefs, which
      allows us not only to deceive others with the explicit intent to create a false
      belief, but it also allows us to put ourselves in others' shoes to determine when
      cheaters need to be punished, even if we are not directly disadvantaged by the
      cheater.

PMID- 27865581
TI  - [Orthostatic hypotension; that great unknown].
AB  - Orthostatic hypotension is an anomaly of growing interest in scientific research.
      Although certain neurogenic diseases are associated with this phenomenon, it can
      also be associated with non-neurological causes. Although orthostatic hypotension
      is defined by consensus as a decrease in the systolic blood pressure of at least
      20mmHg, or a decrease in diastolic blood pressure of at least 10mmHg, within 3min
      of standing, the studies differ on how to diagnose it. Orthostatic hypotension is
      associated with certain cardiovascular risk factors and with drug treatment, but
      the results are contradictory. The purpose of this review is to update the
      knowledge about orthostatic hypotension and its treatment, as well as to propose
      a method to standardise its diagnosis.

PMID- 27865585
TI  - The prevalence of posttraumatic stress disorder in pregnancy and after birth: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Previous reviews have provided preliminary insights into risk factors
      and possible prevalence of Post-traumatic Stress Disorder (PTSD) postpartum with
      no attempt to examine prenatal PTSD. This study aimed to assess the prevalence of
      PTSD during pregnancy and after birth, and the course of PTSD over this time.
      METHODS: PsychINFO, PubMed, Scopus and Web of Science were searched using PTSD
      terms crossed with perinatal terms. Studies were included if they reported the
      prevalence of PTSD during pregnancy or after birth using a diagnostic measure.
      RESULTS: 59 studies (N =24267) met inclusion criteria: 35 studies of prenatal
      PTSD and 28 studies of postpartum PTSD (where 4 studies provided prevalence of
      PTSD in pregnancy and postpartum). In community samples the mean prevalence of
      prenatal PTSD was 3.3% (95%, CI 2.44-4.54). The majority of postpartum studies
      measured PTSD in relation to childbirth with a mean prevalence of 4.0% (95%, CI
      2.77-5.71) in community samples. Women in high-risk groups were at more risk of
      PTSD with a mean prevalence of 18.95% (95%, CI 10.62-31.43) in pregnancy and
      18.5% (95%, CI 10.6-30.38) after birth. Using clinical interviews was associated
      with lower prevalence rates in pregnancy and higher prevalence rates postpartum.
      LIMITATIONS: Limitations include use of stringent diagnostic criteria, wide
      variability of PTSD rates, and inadequacy of studies on prenatal PTSD measured in
      three trimesters. CONCLUSIONS: PTSD is prevalent during pregnancy and after birth
      and may increase postpartum if not identified and treated. Assessment and
      treatment in maternity services is recommended.

PMID- 27865586
TI  - Erythropoietin induces production of hepatocyte growth factor from bone marrow
      mesenchymal stem cells in vitro.
AB  - BACKGROUND: Hepatocyte Growth Factor (HGF) plays a pivotal role in hematopoiesis,
      motility, growth and mobilization of hematopoietic stem/progenitor cells (HSPCs).
      HGF mainly is produced by bone marrow mesenchymal stem cells (BM-MSCs). MSCs
      express erythropoietin (EPO) receptor. In this study, we aimed to assess the
      effect of EPO on HGF secretion in BM-MSCs. METHODS: The BM-MSCs treated with EPO
      (4 IU/ml) for 6, 24 and 48 h. HGF gene expression and protein level were assessed
      using quantitative real time PCR (qRT-PCR) and Enzyme-linked immunosorbant Assay.
      In order to show the effect of secreted HGF on migration of HSPCs, hematopoietic
      stem cells (HSCs) were isolated from cord blood and evaluated using transwell
      migration assay. RESULTS: We observed a significant increase in level of HGF in
      cell supernatant after 48 h compared to control group (P < 0.05). Also, qRT-PCR
      results demonstrated a significant elevation in HGF expression level after 24 and
      48 h treatment with EPO compared to control group (P < 0.05). Finally, migration
      assay results showed a significant increase in migration of HSCs in treated group
      after 48 h. CONCLUSION: Our data indicated that EPO may play an important role in
      stem cell mobilization through up regulating HGF in MSCs and inducing migration
      of HSCs.

PMID- 27865587
TI  - [A new history...].

PMID- 27865589
TI  - Discussion.

PMID- 27865588
TI  - Pediatric patients with pheochromocytoma and paraganglioma should have routine
      preoperative genetic testing for common susceptibility genes in addition to
      imaging to detect extra-adrenal and metastatic tumors.
AB  - BACKGROUND: Pediatric pheochromocytomas and paragangliomas are rare with limited
      data on the optimal management approach. The aim of this study was to determine
      the role of genetic testing and imaging to detect extra-adrenal and/or metastatic
      tumors in pediatric pheochromocytomas and paragangliomas. METHODS: We performed a
      retrospective study of 55 patients diagnosed at <=21 years of age with
      pheochromocytomas and paragangliomas with analysis of data on genetic testing and
      multimodal imaging. RESULTS: Eighty percent of patients (n = 44/55) had a
      germline mutation. The majority were found to have either VHL (38%) or SDHB (25%)
      mutation. Pheochromocytoma was present in 67% (n = 37/55) of patients and was
      bilateral in 51% (n = 19/37). The majority of patients with bilateral
      pheochromocytomas had VHL (79%). Abdominal paragangliomas was present in 22% (n =
      12/55), head and neck paragangliomas in 11% (n = 6/55), and thoracic
      paragangliomas in 2 of 55 patients. For paragangliomas, SDHx accounted for 72% (n
      = 13/18) of mutations. The rate of malignancy was 16% (n = 9/55), 56% of whom had
      SDHB mutations. In two-thirds of patients, functional imaging identified either
      extra-adrenal paragangliomas and/or metastatic disease. CONCLUSION: The majority
      of pediatric patients with pheochromocytomas and paragangliomas have detectable
      germline mutations. Therefore, we suggest strongly that all pediatric patients
      with pheochromocytomas and paragangliomas undergo genetic testing and imaging to
      detect extra-adrenal paragangliomas and metastatic disease to guide treatment and
      follow-up.

PMID- 27865590
TI  - Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after
      distal pancreatectomy.
AB  - BACKGROUND: Postoperative pancreatic fistula represents the most important
      complication after distal pancreatectomy. The aim of this study was to evaluate
      the use of a preoperative endoscopic injection of botulinum toxin into the
      sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical
      Trials Register number: DRKS00007885). METHODS: This was an investigator
      initiated, prospective clinical phase I/II trial with an exploratory study
      design. We included patients who underwent preoperative endoscopic sphincter
      botulinum toxin injection (100 units of Botox). End points were the feasibility,
      safety, and postoperative outcomes, including postoperative pancreatic fistula
      within 30 days after distal pancreatectomy. Botulinum toxin patients were
      compared with a control collective of patients undergoing distal pancreatectomy
      without botulinum toxin injection by case-control matching in a 1:1 ratio.
      RESULTS: Between February 2015 and February 2016, 29 patients were included. All
      patients underwent successful sphincter of Oddi botulinum toxin injection within
      a median of 6 (range 0-10) days before operation. One patient had an
      asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after
      injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were
      not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased
      amylase levels in drainage fluid on postoperative day 3 (the International Study
      Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade
      A) without symptoms or need for reintervention. Importantly, no clinically
      relevant fistulas (International Study Group of Pancreatic Surgery grades B/C)
      were observed in botulinum toxin patients compared to 33% postoperative
      pancreatic fistula grade B/C in case-control patients (P < .004). CONCLUSION:
      Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe
      approach to decrease the incidence of clinically relevant postoperative
      pancreatic fistula after distal pancreatectomy. The results of the present trial
      suggest its efficacy in the prevention of clinically relevant postoperative
      pancreatic fistula and are validated currently in the German Federal Government
      sponsored, multicenter, randomized controlled PREBOT trial.

PMID- 27865591
TI  - Outcome of adrenalectomy for subclinical hypercortisolism and Cushing syndrome.
AB  - BACKGROUND: We compared operative and metabolic outcomes in patients with
      subclinical Cushing syndrome and Cushing syndrome caused by unilateral adrenal
      lesion, aiming to clarify the role of glucocorticoid replacement treatment in
      patients with subclinical Cushing syndrome after adrenalectomy. METHODS: The
      medical records of all the patients who underwent unilateral adrenalectomy for
      subclinical Cushing syndrome or Cushing syndrome were reviewed. Diagnostic
      criteria for subclinical Cushing syndrome were a pathologic dexamethasone
      suppression test plus 2 additional criteria. RESULTS: Twenty-nine patients with
      subclinical Cushing syndrome and 50 with Cushing syndrome were identified. No
      significant difference was found between patients with subclinical Cushing
      syndrome and Cushing syndrome regarding lesion size, operative time, and hospital
      stay. Two patients out of 29 with subclinical Cushing syndrome and 3 out of 50
      patients with Cushing syndrome experienced Clavien-Dindo grade II complications
      (P = .87). All the patients required postoperative glucocorticoid replacement
      that was discontinued within 6 months in 28 of the 29 patients with subclinical
      Cushing syndrome and in 3 out of 50 Cushing syndrome patients (P < .005). At long
      term follow-up, adrenalectomy significantly improved hypertension and diabetes in
      affected patients, with no differences between subclinical Cushing syndrome and
      Cushing syndrome. Hypercortisolism was resolved in all the cases. CONCLUSION:
      Operative and metabolic outcomes of adrenalectomy are similar in subclinical
      Cushing syndrome and Cushing syndrome. Postoperative glucocorticoid replacement
      treatment is advisable in all patients with subclinical Cushing syndrome.
      Prolonged adrenal insufficiency is more frequent in Cushing syndrome patients.

PMID- 27865594
TI  - Editorial: The role of intraoperative physiologic data in contemporary thyroid
      surgery.

PMID- 27865593
TI  - Identification of novel therapeutic targets in anaplastic thyroid carcinoma using
      functional genomic mRNA-profiling: Paving the way for new avenues?
AB  - BACKGROUND: Currently, anaplastic thyroid carcinoma has a very poor prognosis and
      there is an unmet need for new therapeutic options. Therefore, this study aims to
      identify upregulated genes in anaplastic thyroid carcinoma with known drug
      interactions that could serve as new therapeutic targets. METHODS: Publicly
      available microarray expression profiles of anaplastic thyroid carcinoma and
      normal thyroid tissue were collected. FGmRNA-profiling was applied, which is a
      recently developed method that enhances the ability to capture the downstream
      effects of genomic alterations on gene expression levels. Next, a comparison
      between FGmRNA-profiles of anaplastic thyroid carcinoma and normal thyroid
      samples was performed. Significantly upregulated genes in ATC were prioritized
      based on: 1) known interaction with antineoplastic drugs, 2) current drug
      development status in human, and 3) association with biologic pathways known to
      be involved in anaplastic thyroid carcinoma carcinogenesis. RESULTS: In the
      study, 25 anaplastic thyroid carcinoma and 80 normal thyroid samples were
      included for FGmRNA-profiling. Class comparison identified 301 significantly
      upregulated genes. Following prioritization, MTOR, MET, WEE1, PSMD1, MERTK,
      FGFR3, RARG, and ESR2 were identified as potential therapeutic targets.
      CONCLUSION: We prioritized 8 potential therapeutic druggable targets in
      anaplastic thyroid carcinoma. Ultimately, inhibition of these therapeutic targets
      might improve patient outcome in anaplastic thyroid carcinoma by reducing
      locoregional disease and distant metastases.

PMID- 27865592
TI  - Parathyroidectomy for primary hyperparathyroidism improves sleep quality: A
      prospective study.
AB  - BACKGROUND: This prospective survey study assessed changes in sleep quality in
      patients with primary hyperparathyroidism after parathyroidectomy. METHODS:
      Patients undergoing parathyroidectomy for primary hyperparathyroidism (n = 110)
      or thyroidectomy for benign euthyroid disease (control group; n = 45) were
      recruited between June 2013 and June 2015 and completed the Pittsburgh Sleep
      Quality Index preoperatively and at 1- and 6 months postoperatively. "Poor" sleep
      quality was defined as a score >5; a clinically important and relevant
      improvement was a >=3-point decrease. RESULTS: Preoperatively, parathyroid
      patients had worse sleep quality than thyroid patients (mean 8.1 vs 5.3; P <
      .001); 76 (69%) parathyroid and 23 (51%) thyroid patients reported poor sleep
      quality (P = .03). Postoperatively, only parathyroid patients demonstrated
      improvement in sleep quality; mean scores did not differ between the parathyroid
      and thyroid groups at 1 month (6.3 vs 5.3; P = .12) or 6 months (5.8 vs 4.6; P =
      .11). The proportion of patients with a clinically important improvement in sleep
      quality was greater in the parathyroid group at 1 month (37% vs 10%; P < .001)
      and 6 months (40% vs 17%; P = .01). Importantly, there was no difference in the
      proportion of patients with poor sleep quality between the 2 groups at 1 month
      (50% vs 40%; P = .32) and 6 months (40% vs 29%; P = .22). CONCLUSION: More than
      two-thirds of patients with primary hyperparathyroidism report poor sleep
      quality. After parathyroidectomy, over one-third experienced improvement,
      typically within the first month postoperatively.

PMID- 27865595
TI  - Of mice and men(in) and what I have learned from both.

PMID- 27865596
TI  - Discussion.

PMID- 27865597
TI  - Expert consensus of general surgery residents' proficiency with common endocrine
      operations.
AB  - BACKGROUND: Proficiency with common endocrine operations is expected of
      graduating, general surgery residents. However, no expert consensus guidelines
      exist about these expectations. METHODS: Members of the American Association of
      Endocrine Surgeons were surveyed about their opinions on resident proficiency
      with common endocrine operations. RESULTS: Overall response rate was 38%. A total
      of 92% of the respondents operate with residents. On average, they believed that
      the steps of a total thyroidectomy for benign disease and a well-localized
      parathyroidectomy could be performed by a postgraduate year 4 surgery resident.
      Specific steps that they thought might require more training included decisions
      to divide the strap muscles or leaving a drain. Approximately 66% of respondents
      thought that a postgraduate year 5 surgery resident could independently perform a
      total thyroidectomy for benign disease, but only 45% felt similarly for malignant
      thyroid disease; 79% thought that a postgraduate year 5 surgery resident could
      independently perform a parathyroidectomy. Respondents' years of experience
      correlated with their opinions about resident autonomy for total thyroidectomy
      (benign r = 0.38, P < .001; malignant r = 0.29, P = .001) but not
      parathyroidectomy. On multivariate analysis, sex and years of experience of the
      respondents were independently associated with opinions on autonomy but only for
      total thyroidectomy for benign disease (P = .001). Annual endocrine volume of the
      respondents did not correlate with beliefs in autonomy. CONCLUSION: There was
      general agreement among responding members of the AAES about resident proficiency
      and autonomy with common endocrine operations. As postgraduate year 5 residents
      may not be proficient in advanced endocrine operations, opportunities exist to
      improve training prior to the transition to independent practice for graduates
      that anticipate performing endocrine operations routinely.

PMID- 27865598
TI  - Suppression of cytochrome P450 4B1: An early event in adrenocortical
      tumorigenesis.
AB  - BACKGROUND: Adrenocortical carcinoma is a rare neoplasm with a poor prognosis.
      Conversely, adrenocortical adenomas are common and benign. Despite their shared
      histologic origin, little evidence exists to suggest that adrenocortical adenoma
      arises from adrenocortical carcinoma. Recent genetic analyses of adrenocortical
      carcinoma have shown recurrent gene copy deletion of CYP4B1, a cytochrome P450
      isozyme. This study investigates a potential role for CYP4B1 in modulating
      adrenocortical tumorigenesis and/or conferring chemoresistance to adrenocortical
      carcinomas. METHODS: Using TaqMan, real-time quantitative polymerase chain
      reaction techniques, we investigated CYP4B1 expression in normal adrenal cortex
      (n = 10), histologically confirmed adrenocortical adenomas (n = 10), and
      adrenocortical carcinomas (n = 10). Adrenocortical carcinoma cell lines were
      enforced to express CYP4B1, and effects on cell death and enhanced mitotane and
      cisplatin sensitivity were tested. RESULTS: Gene expression analyses demonstrated
      suppression of CYP4B1 in 100% of both the adrenocortical adenomas (10/10) and
      adrenocortical carcinomas (10/10) tested. Average relative expression of CYP4B1
      was decreased at 0.19 (0.01-0.50; P < .01) in adrenocortical adenomas and nearly
      absent in adrenocortical carcinomas (0.01; 0.00-0.05; P < .01). Protein
      expression correlated with mRNA expression. Ectopic expression of CYP4B1 promoted
      cytotoxicity and increased chemosensitivity in adrenocortical carcinoma cell
      lines. CONCLUSION: CYP4B1 is silenced in both benign and malignant adrenocortical
      tumors and may contribute to tumorigenesis and chemoresistance. Sensitization of
      adrenocortical carcinoma cells engineered to overexpress CYP4B1 further supports
      this notion.

PMID- 27865600
TI  - Discussion.

PMID- 27865599
TI  - Discussion.

PMID- 27865601
TI  - Discussion.

PMID- 27865603
TI  - Discussion.

PMID- 27865602
TI  - Evolution and impact of lymph node dissection during pancreaticoduodenectomy for
      pancreatic cancer.
AB  - BACKGROUND: Insufficient examination of lymph nodes after pancreaticoduodenectomy
      can lead some pancreatic cancer patients with N1 disease to be misclassified as
      N0. We examined trends in lymph node dissection throughout time and investigated
      how these changes affect lymph node status and its prognostic value. METHODS: The
      National Cancer Data Base was queried for patients with nonmetastatic pancreatic
      adenocarcinoma (2004-2013) who underwent classic pancreaticoduodenectomy with
      antrectomy. Logistic regression was performed for odds of node positivity. Kaplan
      Meier curves and Cox proportional hazards models were used to assess the impact
      of lymph node status on overall survival for patients diagnosed during 2-year
      intervals from 2004-2012. RESULTS: Median number of examined lymph nodes was 10
      (interquartile range 6-15) in 2004 vs 17 (interquartile range 12-24) in 2013.
      Number of lymph nodes examined was a significant predictor of N1 disease (P <
      .0001), with a plateau at 30 nodes. N1 disease increased from 64.4% to 68.0% (P <
      .0001). Survival for both N1 and N0 subgroups improved. In successive
      multivariate models, N0 versus N1 status was consistently protective for overall
      survival (P < .0001), but there was no change in the magnitude of its hazard
      ratio over time (overall hazard ratio 0.691; 95% confidence interval 0.660
      0.723). CONCLUSION: Contemporary patients have an adequate number of nodes
      examined during standard pancreaticoduodenectomy. This, along with rising rates
      of N1 cancer detection and improved survival for both node-positive and node
      negative patients, suggest more accurate classification of lymph node status.
      However, no increased benefit is achieved beyond 30 nodes. Overall, lymph node
      status remains a strong prognosticator for overall survival.

PMID- 27865604
TI  - Shorter lives in stingier states: Social policy shortcomings help explain the US
      mortality disadvantage.
AB  - The United States has a mortality disadvantage relative to its political and
      economic peer group of other rich democracies. Recently it has been suggested
      that there could be a role for social policy in explaining this disadvantage. In
      this paper, we test this "social policy hypothesis" by presenting a time-series
      cross-section analysis from 1970 to 2010 of the association between welfare state
      generosity (for unemployment insurance, sickness benefits, and pensions) and life
      expectancy, for the US and 17 other high-income countries. Fixed-effects
      estimation with autocorrelation-corrected standard errors (robust to unmeasured
      between-country differences and serial autocorrelation of repeated measures)
      found strong associations between welfare generosity and life expectancy. A unit
      increase in overall welfare generosity yields a 0.17 year increase in life
      expectancy at birth (p < 0.001), and a 0.07 year increase in life expectancy at
      age 65 (p < 0.001). The strongest effects of the welfare state are in the domain
      of pension benefits (b = 0.439 for life expectancy at birth, p < 0.001; b = 0.199
      for life expectancy at age 65, p < 0.001). Models that lag the measures of social
      policy by ten years produce similar results, suggesting that the results are not
      driven by endogeneity bias. There is evidence that the US mortality disadvantage
      is, in part, a welfare-state disadvantage. We estimate that life expectancy in
      the US would be approximately 3.77 years longer, if it had just the average
      social policy generosity of the other 17 OECD nations.

PMID- 27865605
TI  - Population pharmacokinetic model of lithium and drug compliance assessment.
AB  - Population pharmacokinetic analysis of lithium during therapeutic drug monitoring
      and drug compliance assessment was performed in 54 patients and 246 plasma
      concentrations levels were included in this study. Patients received several
      treatment cycles (1-9) and one plasma concentration measurement for each patient
      was obtained always before starting next cycle (pre-dose) at steady state. Data
      were analysed using the population approach with NONMEM version 7.2. Lithium
      measurements were described using a two-compartment model (CL/F=0.41Lh-1,
      V1/F=15.3L, Q/F=0.61Lh-1, and V2/F = 15.8L) and the most significant covariate on
      lithium CL was found to be creatinine clearance (reference model). Lithium
      compliance was analysed using inter-occasion variability or Markovian features
      (previous lithium measurement as ordered categorical covariate) on
      bioavailability parameter. Markov-type model predicted the lithium compliance in
      the next cycle with higher success rate (79.8%) compared to IOV model (65.2%) and
      reference model (43.2%). This model becomes an efficient tool, not only being
      able to adequately describe the observed outcome, but also to predict the
      individual drug compliance in the next cycle. Therefore, Bipolar disorder
      patients can be classified regarding their probability to become extensive or
      poor compliers in the next cycle and then, individual probabilities lower than
      0.5 highlight the need of intensive monitoring, as well as other pharmaceutical
      care measurements that might be applied to enhance drug compliance for a better
      and safer lithium treatment.

PMID- 27865606
TI  - Arsenic contamination in agricultural soils of Bengal deltaic region of West
      Bengal and its higher assimilation in monsoon rice.
AB  - In the Bengal deltaic region, the shallow groundwater laced with arsenic is used
      for irrigation frequently and has elevated the soil arsenic in agricultural soil.
      However, the areas with seasonal flooding reduce arsenic in top layers of the
      soils. Study shows arsenic accumulation in the deeper soil layers with time in
      the contaminated agricultural soil (19.40+/-0.38mg/kg in 0-5cm, 27.17+/-0.44mg/kg
      in 5-10cm and 41.24+/-0.48mg/kg in 10-15cm) in 2013 whereas depletion in 2014 and
      its buildup in different parts of monsoon rice plant in Nadia, India. Principal
      Component Analysis and Cluster Analysis were performed, and Enrichment Factor was
      calculated to identify the sources of arsenic in the soil. Potential Ecological
      Risk was also calculated to estimate the extent of risk posed by arsenic in soil,
      along with the potential risk of dietary arsenic exposure. Remarkably, the
      concentration of arsenic detected in the rice grain showed average value of
      1.4mg/kg in 2013 which has increased to 1.6 in 2014, both being above the
      permissible limit (1mg/kg). These results indicate that monsoon flooding enhances
      the infiltration of arsenic in the deeper soil layer, which lead to further
      contamination of shallow groundwater.

PMID- 27865608
TI  - Benefit in long-term response and mortality of treatment with intravenous
      immunoglobulin prior to plasmapheresis in peripheral polyneuropathies.
AB  - OBJECTIVES: The benefits of plasmapheresis (PA) for neurologic autoimmune
      diseases have been widely demonstrated. Little is known about the long-term
      neurologic prognosis and course after PA and immunosuppressive (IS) and/or
      intravenous immunoglobulin (IVIG) treatment. We aimed to analyse features
      associated with short-term response and long-term outcome and prognosis
      (neurologic status and mortality) of peripheral polyneuropathy (PP) and central
      nervous system acute inflammatory disease (CNSAID) treated with PA. PATIENTS AND
      METHODS: A descriptive, retrospective single-centre study from January 2005 to
      December 2012. RESULTS: There were 26 episodes, which included 16 CNSAID and 10
      PP cases. First line therapy included PA (n=4), IS drugs (n=15), and IVIG (n=7).
      Responses were achieved in 80% and 50% of PP and CNSAID cases, respectively. For
      PP, first line treatment with IVIG and no IS treatment prior to or during PA were
      variables associated with short-term response (P=0.067), good or stable
      neurologic status at the end of follow-up (P=0.008), and lower mortality rate
      (P=0.008). For CNSAID, initial EDSS score>=7 (P=0.019) was related to long-term
      good or stable neurologic status. During the study period, 177 sessions were
      conducted; 3.4% had technical complications and 8.5% clinical complications.
      However, these incidents were all minor and no PA session had to be discontinued.
      CONCLUSION: The response rates achieved in our patients were similar to those of
      other research. PA has a safe profile but double-blind, controlled studies are
      needed to evaluate the synergy of sequential treatment with IGIV followed by PA
      and the possible benefit for long-term outcome.

PMID- 27865609
TI  - Recent Advances in Lipid-Based Vesicles and Particulate Carriers for Topical and
      Transdermal Application.
AB  - In the recent decade, skin delivery (topical and transdermal) has gained an
      unprecedented popularity, especially due to increased incidences of chronic skin
      diseases, demand for targeted and patient compliant delivery, and interest in
      life cycle management strategies among pharmaceutical companies. Literature
      review of recent publications indicates that among various skin delivery systems,
      lipid-based delivery systems (vesicular carriers and lipid particulate systems)
      have been the most successful. Vesicular carriers consist of liposomes,
      ultradeformable liposomes, and ethosomes, while lipid particulate systems consist
      of lipospheres, solid lipid nanoparticles, and nanostructured lipid carriers.
      These systems can increase the skin drug transport by improving drug
      solubilization in the formulation, drug partitioning into the skin, and
      fluidizing skin lipids. Considering that lipid-based delivery systems are
      regarded as safe and efficient, they are proving to be an attractive delivery
      strategy for the pharmaceutical as well as cosmeceutical drug substances.
      However, development of these delivery systems requires comprehensive
      understanding of physicochemical characteristics of drug and delivery carriers,
      formulation and process variables, mechanism of skin delivery, recent
      technological advancements, specific limitations, and regulatory considerations.
      Therefore, this review article encompasses recent research advances addressing
      the aforementioned issues.

PMID- 27865610
TI  - Assessment of Bioequivalence of Weak Base Formulations Under Various Dosing
      Conditions Using Physiologically Based Pharmacokinetic Simulations in Virtual
      Populations. Case Examples: Ketoconazole and Posaconazole.
AB  - Postabsorptive factors which can affect systemic drug exposure are assumed to be
      dependent on the active pharmaceutical ingredient (API), and thus independent of
      formulation. In contrast, preabsorptive factors, for example, hypochlorhydria,
      might affect systemic exposure in both an API and a formulation-dependent way.
      The aim of this study was to evaluate whether the oral absorption of 2 poorly
      soluble, weakly basic APIs, ketoconazole (KETO) and posaconazole (POSA), would be
      equally sensitive to changes in dissolution rate under the following dosing
      conditions-coadministration with water, with food, with carbonated drinks, and in
      drug-induced hypochlorhydria. The systems-components of validated absorption and
      PBPK models for KETO and POSA were modified to simulate the above-mentioned
      clinical scenarios. Virtual bioequivalence studies were then carried out to
      investigate whether formulation effects on the plasma profile vary with the
      dosing conditions. The slow precipitation of KETO upon reaching the upper part of
      the small intestine renders its absorption more sensitive to the completeness of
      gastric dissolution and thus to the gastric environment than POSA, which is
      subject to extensive precipitation in response to a pH shift. The virtual
      bioequivalence studies showed that hypothetical test and reference formulations
      containing KETO would be bioequivalent only if the microenvironment in the
      stomach enables complete gastric dissolution. We conclude that physiologically
      based pharmacokinetic modeling and simulation has excellent potential to address
      issues close to bedside such as optimizing dosing conditions. By studying virtual
      populations adapted to various clinical situations, clinical strategies to reduce
      therapeutic failures can be identified.

PMID- 27865607
TI  - DNA modifications in models of alcohol use disorders.
AB  - Chronic alcohol use and abuse result in widespread changes to gene expression,
      some of which contribute to the development of alcohol-use disorders (AUD). Gene
      expression is controlled, in part, by a group of regulatory systems often
      referred to as epigenetic factors, which includes, among other mechanisms,
      chemical marks made on the histone proteins around which genomic DNA is wound to
      form chromatin, and on nucleotides of the DNA itself. In particular, alcohol has
      been shown to perturb the epigenetic machinery, leading to changes in gene
      expression and cellular functions characteristic of AUD and, ultimately, to
      altered behavior. DNA modifications in particular are seeing increasing research
      in the context of alcohol use and abuse. To date, studies of DNA modifications in
      AUD have primarily looked at global methylation profiles in human brain and
      blood, gene-specific methylation profiles in animal models, methylation changes
      associated with prenatal ethanol exposure, and the potential therapeutic
      abilities of DNA methyltransferase inhibitors. Future studies may be aimed at
      identifying changes to more recently discovered DNA modifications, utilizing new
      methods to discriminate methylation profiles between cell types, thus clarifying
      how alcohol influences the methylomes of cell-type populations and how this may
      affect downstream processes. These studies and more in-depth probing of DNA
      methylation will be key to determining whether DNA-level epigenetic regulation
      plays a causative role in AUD and can thus be targeted for treatment of the
      disorder.

PMID- 27865612
TI  - Changes in intestinal immunity, gut microbiota, and expression of energy
      metabolism-related genes explain adenoma growth in bilberry and cloudberry-fed
      ApcMin mice.
AB  - We showed previously that ellagitannin-rich cloudberries and anthocyanin-rich
      bilberries reduce the number of intestinal adenomas in multiple intestinal
      neoplasia/+ (ApcMin) mice. We also found that cloudberries decreased the size of
      adenomas, whereas bilberries increased it. Here we hypothesized that the
      difference in adenoma growth could be explained by dissimilar effects of the
      berries on intestinal immune responses and gut microbiota, potentially driven by
      the distinct polyphenol compositions of the 2 berries. Our objectives were to
      investigate lymphocyte subtypes and the predominant cecal bacterial diversity in
      mice fed with bilberries and cloudberries, and to analyze global gene expression
      profiles in the intestinal mucosa. Immunostainings of CD3+ T lymphocytes, FoxP3+
      regulatory T lymphocytes, and CD45R+ B lymphocytes revealed a smaller ratio of
      intraepithelial to all mucosal CD3+ T lymphocytes in the cloudberry-fed mice
      compared with controls, suggesting an attenuation of inflammation. Bilberry
      feeding induced no changes in the density of any of the lymphocyte subtypes. The
      predominant bacterial diversity in cecal contents, analyzed using polymerase
      chain reaction-denaturating gradient gel electrophoresis, was higher in the
      bilberry group than in the control or cloudberry groups. The microbial profiles
      of cloudberry-fed mice clustered together and were associated with small adenoma
      size. Pathway analyses of gene expression data showed that cloudberry down
      regulated and bilberry up-regulated the expression of energy metabolism-related
      genes in the intestinal mucosa. In conclusion, attenuation of intestinal
      inflammation, changes in microbial profiles, and down-regulation of mucosal
      energy metabolism may account for the smaller adenoma size in cloudberry-fed mice
      in comparison to bilberry-fed mice.

PMID- 27865611
TI  - Treatment of osteonecrosis of the femoral head with free vascularized fibular
      grafting: Results of 7.6-year follow-up.
AB  - OBJECTIVES: The aim of this study was to determine long term follow up of the
      patients who had femoral head osteonecrosis and had been treated with free
      vascularized fibular grafting. PATIENTS AND METHODS: We retrospectively reviewed
      28 hips of 21 patients who had undergone free vascularized fibular grafting for
      the treatment of osteonecrosis of femoral head. There were 16 male and 5 female
      patients. The mean age of the patients at the time of surgery was 30.7 years
      (between 15 and 53 years). The mean follow-up time was 7.6 years (between 5 years
      and 9.2 years). RESULTS: During follow-up, one patient died because of leukemia,
      and one patient was lost. The remaining 26 hips of 19 patients were evaluated.
      According to the Ficat classification, at the time of surgery, 17 hips were in
      grade 2 and 9 hips were in grade 3. The post-operative Harris hip scores in grade
      II disease were excellent in 12 patients, good in 3 patients, and fair in 1
      patient. In grade III disease, 1 patient was excellent, 5 patients were good, and
      1 patient was fair. There was a significant increase in HHS scores (61 +/- 9.7 vs
      84 +/- 17.8, p < 0.001). CONCLUSION: Free vascularized fibular grafting yields
      extremely good results, particularly in pre-collapse stages of disease in young
      patients. The operation time does not mark increased if the surgical team is
      "familiar" with the procedure, and the residual fibular defect of the donor site
      does not impair the functions of daily living. LEVEL OF EVIDENCE: Level IV,
      Therapeutic study.

PMID- 27865614
TI  - Plasma eicosapentaenoic acid is negatively associated with all-cause mortality
      among men and women in a population-based prospective study.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties,
      whereas omega-6 PUFAs appear to have proinflammatory properties. We aimed to
      assess plasma omega-3 and omega-6 PUFA status in relation to all-cause mortality
      in an Australian community-based study. We hypothesized that omega-3 PUFA would
      be inversely associated, and omega-6 PUFA positively associated with all-cause
      mortality. Plasma phospholipid omega-3 (eicosapentaenoic acid [EPA],
      docosapentaenoic acid [DPA], docosahexaenoic acid, alpha-linolenic acid, and
      total) and omega-6 PUFAs (linoleic acid, arachidonic acid, and total) were
      measured among 1008 adults (44% men) in 1996. Plasma PUFA composition was
      quantified using gas chromatography. During 17-year follow-up, 98 men and 81
      women died. After adjustment for potential confounding factors, plasma EPA was
      inversely associated with all-cause mortality overall (adjusted hazard ratio [HR]
      per 1-SD increase, 0.81; 95% confidence interval [CI], 0.68-0.95), in men (HR,
      0.78; 95% CI, 0.62-0.98), and in women (HR, 0.78; 95% CI, 0.65-0.94), separately.
      Inverse associations with mortality among men were also seen for DPA (HR, 0.76;
      95% CI, 0.60-0.97) and alpha-linolenic acid (HR, 0.73; 95% CI, 0.57-0.94). No
      omega-6 PUFAs were significantly associated with mortality. Our findings of
      reduced all-cause mortality in men and women who have high EPA in plasma, and in
      men with high plasma DPA and alpha-linolenic acid, partially support our
      hypothesis that omega-3 PUFAs help reduce mortality but provide no evidence that
      omega-6 PUFAs may increase mortality.

PMID- 27865613
TI  - Hyperglycemia, oxidative stress, liver damage and dysfunction in alloxan-induced
      diabetic rat are prevented by Spirulina supplementation.
AB  - Medicinal plants have long been used against life-threatening diseases including
      diabetes, with more or less success. Some of these plants have been shown to
      possess antioxidant activities, which could help improving diabetes
      inconveniences. In that context, we investigated the effects of spirulina
      supplementation on alloxan-induced diabetic rats, hypothesizing that co
      administration of spirulina with rat diet could ameliorate diabetes complications
      and provide as benefits as the common antidiabetic insulin. Following alloxan
      treatment, male Wistar rats were fed daily with 5% spirulina-enriched diet or
      treated with insulin (0.5 IU/rat) for 21 days. Both spirulina and insulin
      treatments of diabetic rats resulted in a significant reduction in fasting blood
      glucose and an increase of glycogen level. Spirulina supplementation also impeded
      loss of body weight and ameliorated hepatic toxicity indices, i.e. alkaline
      phosphatases and transaminases activities, bilirubin levels and lipid
      peroxidation. Besides, triglycerides, total cholesterol, and low-density
      lipoprotein cholesterol levels decreased in the serum. Moreover, diabetic rats
      fed with spirulina exhibited sig changes in antioxidant enzyme activities in the
      liver (ie, decrease in superoxide dismutase and increase in catalase and
      glutathione peroxidase activities). The beneficial effects of spirulina or
      insulin were confirmed by histological study of the liver of diabetic rats.
      Overall, this study indicates that treatment with spirulina decreased
      hyperglycemia and oxidative stress in diabetic rats, this amelioration being even
      more pronounced than that provided by insulin injection. Therefore,
      administration of this alga would be very helpful in the prevention of diabetic
      complications.

PMID- 27865616
TI  - Phenylpropanoids from cinnamon bark reduced beta-amyloid production by the
      inhibition of beta-secretase in Chinese hamster ovarian cells stably expressing
      amyloid precursor protein.
AB  - beta-Amyloid (Abeta) is a substance of Alzheimer disease (AD), which is generated
      via the amyloidogenic pathway from amyloid precursor protein (APP) by beta
      secretase and gamma-secretase. Inhibition of Abeta production is a potential
      therapeutic approach to AD. Thus, we tested the hypothesis that cinnamon bark
      (Cinnamomi Cortex Spissus), the dried bark of Cinnamomum cassia Blume
      (Lauraceae), and its constituents are beneficial to AD. The methanol extract of
      cinnamon bark efficiently reduced Abeta40 production in Chinese hamster ovarian
      (CHO) cells stably expressing APP as determined by enzyme-linked immunosorbent
      assay. Bioassay-guided isolation of cinnamon bark extract was carried out using
      open column chromatography and high-performance liquid chromatography, and the
      following 6 phenylpropanoids were isolated: syringaresinol (1); medioresinol (2);
      coumarin (3); 2-hydroxycinnamaldehyde (4); cryptamygin A (5); and 3',5,7
      trimethoxy epicatechin (6). Among these, 4 MUg/mL medioresinol and cryptamygin A
      reduced Abeta40 production by 50% and 60%, respectively, compared with dimethyl
      sulfoxide-treated control cells. The IC50 values of medioresinol and cryptamygin
      A for the inhibition of Abeta40 production were 10.8 and 8.2 MUg/mL,
      respectively. Furthermore, treatment of APP-CHO cells with either compound
      decreased the amount of beta-secretase and sAPPbeta (the proteolytic fragment of
      APP catalyzed by beta-secretase). These results suggest that the
      antiamyloidogenic activity of cinnamon bark extract was exerted by medioresinol
      and cryptamygin A via a reduction in the amount of beta-secretase. The extract of
      cinnamon bark contains potentially valuable antiamyloidogenic agents for the
      prevention and treatment of AD.

PMID- 27865617
TI  - Panaxatriol derived from ginseng augments resistance exercised-induced protein
      synthesis via mTORC1 signaling in rat skeletal muscle.
AB  - Resistance exercise activates muscle protein synthesis via the mammalian target
      of rapamycin complex 1 (mTORC1) pathway and subsequent muscle hypertrophy.
      Upstream components of the mTORC1 pathway are widely known to be involved in Akt
      and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. Previous
      studies have shown that ginseng stimulated Akt and ERK1/2 signaling. Therefore,
      we hypothesized that panaxatriol (PT) derived from ginseng triggers mTORC1
      signaling and muscle protein synthesis by activating both the Akt and ERK1/2
      signaling pathways, and that PT additively stimulates muscle protein synthesis
      when combined with resistance exercise. The study included male Sprague-Dawley
      rats. The legs of the rats were divided into control, PT-only, exercise-only, and
      exercise + PT groups. The right legs were subjected to isometric resistance
      exercise using percutaneous electrical stimulation, whereas the left legs were
      used as controls. PT (0.2 g/kg) was administered immediately after exercise. The
      Akt and ERK1/2 phosphorylation levels were significantly higher in the exercise +
      PT group than in the exercise-only group 0.5 hour after exercise. The
      phosphorylation of p70S6K was significantly increased at both 0.5 and 3 hours
      after exercise, and it was higher in the exercise + PT group than in the exercise
      only group at both 0.5 and 3 hours after exercise. Muscle protein synthesis was
      significantly increased 3 hours after exercise, and it was higher in the exercise
      + PT group than in the exercise-only group 3 hours after exercise. Our results
      suggest that PT derived from ginseng enhances resistance exercise-induced protein
      synthesis via mTORC1 signaling in rat skeletal muscle.

PMID- 27865615
TI  - Association between the dietary inflammatory index, waist-to-hip ratio and
      metabolic syndrome.
AB  - Inflammation due to poor diet may contribute to the development of metabolic
      syndrome (MetSyn). The Dietary Inflammatory Index (DII) was created to
      characterize diet on a scale from anti- to pro-inflammatory. Our hypothesis was
      that higher (i.e., more pro-inflammatory) DII scores are associated with an
      increased prevalence of MetSyn compared to those with lower (i.e., more anti
      inflammatory) DII scores. Data from the Polish-Norwegian (PONS) Study were
      analyzed using logistic and linear regression procedures in SAS (version 9.4).
      Comparisons of interest were between the first and fourth DII quartiles; analyses
      were stratified by sex. Mean waist-to-hip ratio (WHR) and diastolic blood
      pressure were greater among those in DII quartile 4 compared to 1. No
      statistically significantly increased MetSyn risks were observed for DII quartile
      4 among men or women. Men in DII quartile 4 had elevated odds of fulfilling the
      waist component of MetSyn (odds ratio=1.65, 95% confidence interval=1.01-2.69).
      Although this study benefited from the DII and large sample sizes for both men
      and women, its cross-sectional nature and use of self-reported data may limit
      interpretation of results. Further work must be done in longitudinal studies to
      understand whether pro-inflammatory diets are associated with an increased risk
      of MetSyn, its components or other metabolic-related conditions. Additionally,
      further examination of the DII in relation to body habitus will be needed to
      understand the role of pro-inflammatory diets on anthropometrics, as observed in
      this study.

PMID- 27865618
TI  - Actinidia arguta supplementation protects aorta and liver in rats with induced
      hypercholesterolemia.
AB  - There are no published results focusing on the study of hardy kiwifruit as a
      supplementation to the atherogenic diet. We hypothesized that hardy kiwifruit
      (Actinidia arguta (A. arguta)) from Poland possess better pro-healthy action than
      two Asian varieties (Hayward and Bidan). We tested this hypothesis by measuring
      the metabolic reactions of rats loaded with 1% cholesterol and supplemented with
      5% of hardy kiwifruit (A. arguta), Hayward, or Bidan in their diets. The
      experiment was performed on 71 male Wistar rats. Cholesterol showed a significant
      impact on the rise of liver somatic index, while lipid profile improved by
      decreasing the levels of TC, LDL-C, TC/HDL-C, AI, TG, and increasing HDL-C in the
      serum of rats (P<.05). Total plasma antioxidant capacity determined by ABTS,
      FRAP, and DPPH assays was increased. ALP in rat serum was higher in groups
      receiving cholesterol diets and kiwifruit. A decrease in fibrinogen as well as
      prolonged prothrombin time and a reduction of the MPO in serum were estimated.
      The smallest percentage of lesions in the aortic arch was in the ChGeneva,
      ChWeiki, and ChAnna. Similarly, the smallest fatty liver disease was recorded in
      the ChGeneva and ChAnna groups. The distribution of lipids in the liver from
      these groups had a character of "mosaic," in hardy/mini kiwifruit (Jumbo),
      Hayward, and Bidan was distributed uniformly. The longest villi were in ChWeiki,
      and significantly lower in ChHayward and ChBidan. The present results support our
      hypothesis that A. arguta showed better pro-health impacts in rats loaded with
      cholesterol than Hayward and Bidan kiwifruit, and, for the first time, the
      positive nutritional effects of supplemented A. arguta for hypercholesterolemia
      are noted.

PMID- 27865619
TI  - Inhibition on the growth of human MDA-MB-231 breast cancer cells in vitro and
      tumor growth in a mouse xenograft model by Se-containing polysaccharides from
      Pyracantha fortuneana.
AB  - Breast cancer is the second cause of cancer-related death among Women. Current
      therapies for breast cancer have adverse side-effects. Selenium (Se)-containing
      polysaccharides have multiple health benefits to humans. Pyracantha fortuneana
      (P. fortuneana) contains rich Se polysaccharides. We hypothesized that Se
      containing polysaccharides from P. fortuneana possess anticancer activity on
      breast cancer via inhibiting growth and inducing apoptosis. This study aimed to
      assess the anticancer effect of Se-containing polysaccharides from P. fortuneana
      and the underlying mechanisms. Se-containing polysaccharides were purified. Their
      properties and monosaccharide compositions were analyzed. Their effects on cell
      growth, expression of cycle proteins, apoptosis and apoptosis-related protein,
      and tumor growth in mouse xenograft model were examined. This extract contained
      93.7% (w/w) of carbohydrate, 2.1% (w/w) of uronic acid and 3.7MUg/g of Se, and
      was considered as Se-conjugated polysaccharides (Se-PFPs). In vitro studies
      showed that treatment of triple negative breast cancer (TNBC) MDA-MB-231 cells
      with Se-PFPs (1) inhibited cell growth dose-dependently by arresting cells at G2
      phase via inhibiting CDC25C-CyclinB1/CDC2 pathway; (2) caused apoptosis
      associated with increased p53, Bax, Puma and Noxa, decreased Bcl2, increased
      Bax/Bcl2 ratio and increased activities of caspases 3/9, suggesting its effect on
      p53-mediated cytochrome c-caspase pathway. Treatment of nude mice bearing MDA-MB
      231-derived xenograft tumors with Se-PFPs significantly reduced tumor growth
      without altering body weight, confirming its antitumor activity without toxic
      side effects. Se-PFPs enhanced doxorubicin cytotoxic effects. It is concluded
      that Se-containing polysaccharides from P. fortuneana potently inhibit the growth
      and induce apoptosis of TNBC cells and can be potential anticancer agent for
      TNBC.

PMID- 27865621
TI  - Menaquinone-4 (vitamin K2) up-regulates expression of human intestinal alkaline
      phosphatase in Caco-2 cells.
AB  - Alkaline phosphatase (ALP) hydrolyzes several monophosphate esters into inorganic
      acid and alcohol. In humans, 4 kinds of ALP isozymes have been identified: tissue
      nonspecific ALP, intestinal ALP, placental ALP, and germ cell ALP. Intestinal ALP
      is expressed at a high concentration in the brush border membrane of intestinal
      epithelial cells and is known to be affected by several kinds of nutrients, such
      as lipids, but the physiological function of intestinal ALP has remained elusive.
      Vitamin K is an essential cofactor for the posttranslational carboxylation of
      glutamate residues into gamma-carboxy glutamate. Menaquinone-4 (MK-4) with 4
      isoprene units, vitamin K2, has been shown to induce bone-type ALP activity and
      osteoblastogenesis in human bone marrow cells. In this study, we investigated the
      effects of MK-4 on the level of ALP activity and expression of ALP messenger RNA
      in the human colon carcinoma cell line Caco-2, which is known to differentiate
      into small intestinal epithelial cells in vitro. After treatment with MK-4, there
      were significant increases in the ALP activities of Caco-2 cells. Inhibitor and
      thermal inactivation experiments demonstrated that the increased ALP had
      properties of intestinal-type ALP. Semiquantitative reverse transcription
      polymerase chain reaction analysis revealed that expressions of human intestinal
      ALP and sucrase-isomaltase, which are intestinal differentiation markers, were
      highly enhanced in Caco-2 cells by MK-4. This is the first report concerning ALP
      messenger RNA expression induced by vitamin K2 in Caco-2 cells. Further studies
      on the physiological functions of human intestinal ALP will provide useful data
      on the novel effects of vitamin K.

PMID- 27865620
TI  - Consumption of chokeberry (Aronia mitschurinii) products modestly lowered blood
      pressure and reduced low-grade inflammation in patients with mildly elevated
      blood pressure.
AB  - Previous studies suggest that consumption of chokeberries may improve
      cardiovascular disease risk factor profiles. We hypothesized that chokeberries
      (Aronia mitschurinii) have beneficial effects on blood pressure, low-grade
      inflammation, serum lipids, serum glucose, and platelet aggregation in patients
      with untreated mild hypertension. A total of 38 participants were enrolled into a
      16-week single blinded crossover trial. The participants were randomized to use
      cold-pressed 100% chokeberry juice (300 mL/d) and oven-dried chokeberry powder (3
      g/d), or matched placebo products in random order for 8 weeks each with no
      washout period. The daily portion of chokeberry products was prepared from
      approximately 336 g of fresh chokeberries. Urinary excretion of various
      polyphenols and their metabolites increased during the chokeberry period,
      indicating good compliance. Chokeberries decreased daytime blood pressure and low
      grade inflammation. The daytime ambulatory diastolic blood pressure decreased (
      1.64 mm Hg, P = .02), and the true awake ambulatory systolic (-2.71 mm Hg, P =
      .077) and diastolic (-1.62 mm Hg, P = .057) blood pressure tended to decrease.
      The concentrations of interleukin (IL) 10 and tumor necrosis factor alpha
      decreased (-1.9 pg/mL [P = .008] and -0.67 pg/mL [P = .007], respectively) and
      tended to decrease for IL-4 and IL-5 (-4.5 pg/mL [P = .084] and -0.06 pg/mL [P =
      .059], respectively). No changes in serum lipids, lipoproteins, glucose, and in
      vitro platelet aggregation were noted with the chokeberry intervention. These
      findings suggest that inclusion of chokeberry products in the diet of
      participants with mildly elevated blood pressure has minor beneficial effects on
      cardiovascular health.

PMID- 27865622
TI  - Protecting from Envelope Stress: Variations on the Phage-Shock-Protein Theme.
AB  - During envelope stress, critical inner-membrane functions are preserved by the
      phage-shock-protein (Psp) system, a stress response that emerged from work with
      Escherichia coli and other Gram-negative bacteria. Reciprocal regulatory
      interactions and multiple effector functions are well documented in these
      organisms. Searches for the Psp system across phyla reveal conservation of only
      one protein, PspA. However, examination of Firmicutes and Actinobacteria reveals
      that PspA orthologs associate with non-orthologous regulatory and effector
      proteins retaining functions similar to those in Gram-negative counterparts.
      Conservation across phyla emphasizes the long-standing importance of the Psp
      system in prokaryotes, while inter- and intra-phyla variations within the system
      indicate adaptation to different cell envelope structures, bacterial lifestyles,
      and/or bacterial morphogenetic strategies.

PMID- 27865623
TI  - Key role of an ADP - ribose - dependent transcriptional regulator of NAD
      metabolism for fitness and virulence of Pseudomonas aeruginosa.
AB  - NAD is an essential co-factor of redox reactions and metabolic conversions of NAD
      dependent enzymes. NAD biosynthesis in the opportunistic pathogen Pseudomonas
      aeruginosa has yet not been experimentally explored. The in silico search for
      orthologs in the P. aeruginosa PAO1 genome identified the operon pncA - pncB1
      nadE (PA4918-PA4920) to encode the nicotinamidase, nicotinate
      phosporibosyltransferase and Nad synthase of salvage pathway I. The functional
      role of the preceding genes PA4917 and PA4916 was resolved by the
      characterization of recombinant protein. PA4917 turned out to encode the
      nicotinate mononucleotide adenylyltransferase NadD2 and PA4916 was determined to
      encode the transcriptional repressor NrtR that binds to an intergenic sequence
      between nadD2 and pncA. Complex formation between the catalytically inactive
      Nudix protein NrtR and its DNA binding site was suppressed by the antirepressor
      ADP-ribose. NrtR plasposon mutagenesis abrogated virulence of P. aeruginosa
      TBCF10839 in a murine acute airway infection model and constrained its metabolite
      profile. When grown together with other isogenic plasposon mutants, the nrtR
      knock-out was most compromised in competitive fitness to persist in nutrient-rich
      medium in vitro or murine airways in vivo. This example demonstrates how tightly
      metabolism and virulence can be intertwined by key elements of metabolic control.

PMID- 27865624
TI  - W'ALK' Into the Next Stage.
AB  - In 2007, the rearrangement of anaplastic lymphoma kinase (ALK) was identified to
      be associated with the pathogenesis of a subset of patients with non-small-cell
      lung cancer (NSCLC). Surprisingly, approximately 4 years after the discovery of
      ALK rearrangement in lung cancer, the first-in-class ALK inhibitor (ALKi),
      crizotinib, was approved for metastatic ALK-rearranged NSCLC by the US Food and
      Drug Administration. Subsequently, next-generation ALKis, such as alectinib and
      ceritinib, have been developed, and some of them have been applied in the
      clinical setting. Furthermore, various resistance mechanisms against ALKis have
      been gradually elucidated, and treatment strategies according to such resistance
      have been proposed. In addition, novel ALKis exhibit good antitumor efficacy for
      brain metastases. Thus, we now know much about ALK-rearranged NSCLC; however, is
      it enough? Several concerns, such as the optimal sequence of ALKis, significance
      of antiangiogenic therapy, immune checkpoint therapy, and cytotoxic chemotherapy
      in ALK-rearranged NSCLC, should be clearly addressed, which would lead to the
      establishment of optimal treatment strategies and a more prolonged survival in
      patients with ALK rearrangement. Thus, we should w'ALK' into the next stage.

PMID- 27865625
TI  - Second-Line Treatment Selection in Patients With Non-Small-Cell Lung Cancer of
      Adenocarcinoma Histology: Findings From a European Survey of Treating Physicians.
AB  - BACKGROUND: Guidelines provide treatment recommendations for advanced non-small
      cell lung cancer (NSCLC), but physicians must also consider other factors. We
      surveyed physicians treating NSCLC to determine their therapy goals, drivers of
      treatment choice, current prescribing behavior, and therapy expectations.
      MATERIALS AND METHODS: In 2015, an online survey was conducted of 500
      pulmonologists/oncologists treating lung adenocarcinoma in Germany, France,
      Italy, Spain, and the United Kingdom, comprising screening and therapy decision
      questions. RESULTS: On average, physicians had 14.7 years of experience and
      treated 79 patients/3 months with stage IIIb/IV NSCLC. In patients with Eastern
      Cooperative Oncology Group (ECOG) 0-1, "prolonged survival/extending life" was
      the main therapy goal of physicians for first- (63%) and second-line (40%)
      patients; improvement in quality of life (QoL) was the main goal of 14% of
      physicians for second-line patients. For patients with ECOG >=2, the main goal of
      second-line therapy was improvement in QoL (26%) or tumor-related symptoms (23%).
      Most (57%) physicians strongly agreed that they preferred a second-line treatment
      that extends overall survival (OS) while maintaining QoL; their greatest
      dissatisfaction with available second-line treatment options was the inability to
      "stop tumor progression over the long term" (66%). Physicians expected new
      therapies to become available within 12 months that would provide improvements in
      progression-free survival (83%) or OS (69%). CONCLUSION: OS is important for
      second-line treatments in patients with stage IIIb/IV NSCLC, although QoL
      improvements should not be underestimated. This survey highlights the wait faced
      by patients and physicians as treatments transition from clinical trials to
      clinical practice.

PMID- 27865627
TI  - Epidemiology of infections caused by polymyxin-resistant pathogens.
AB  - Confronting the storm of carbapenemase-producing Gram-negative pathogens and thus
      facing the threat of untreatable infections, the medical community revived
      colistin. Not long since its re-introduction and despite the fact that resistance
      to colistin at least in Escherichia coli is rare, chromosomally-mediated colistin
      resistance in metallo-beta-lactamase-producing Klebsiella pneumoniae strains was
      reported in 2004 from Greece. Subsequent studies revealed the highest
      predominance in Italy (38%) and Greece (26%), with colistin-resistant (Col-R)
      strains frequently carrying a carbapenemase. On the other hand, the international
      prevalence of Col-R Acinetobacter baumannii varied, predominantly in Southern
      Europe and Southeast Asia, with rates exceeding 80% in Italy and Greece. Risk
      factors have mainly incriminated the selective pressure of excess consumption of
      colistin both in animals and humans. In November 2015, emergence of plasmid
      mediated colistin resistance due to the mcr-1 gene was reported from China,
      mostly in community-derived E. coli strains. As of 1 September 2016, the mcr-1
      gene was detected in 35 countries worldwide in livestock/retail meat and in human
      sources from 29 and 22 countries, respectively. Heavy usage of polymyxins in
      animals has been incriminated as the reservoir of the mcr-1 gene. Therefore, it
      is imperative that: (i) polymyxins are banned as growth promoters and for
      prophylaxis in animals; (ii) targeted surveillance plus molecular epidemiology is
      performed in hospitals; (iii) carriers or patients infected with isolates
      harbouring both mcr-1 and carbapenemase genes are strictly isolated; (iv)
      susceptibilities are based on exact colistin minimum inhibitory concentration
      (MIC) determination; and (v) rational use of colistin is audited in hospitals.

PMID- 27865628
TI  - The genesis and presentation of anxiety in disorders of autonomic overexcitation.
AB  - INTRODUCTION: We investigated the genesis and presentation of previously-reported
      anxiety in disorders of autonomic overexcitation in relation to interoception,
      body vigilance and trauma to test our hypothesis that patients with the postural
      tachycardia syndrome (PoTS), vasovagal syncope (VVS) and essential hyperhidrosis
      (EH) represent atypical anxiety phenotypes in whom affective symptoms are more
      related to apprehension and vigilance of physiological (interoceptive) feedback
      than neurotic or trauma-related factors. METHODS: The Anxiety Sensitivity Index,
      Body Vigilance Scale, Self-consciousness Scale, Childhood Traumatic Events Scale
      and heartbeat tracking tasks were completed by 23 healthy controls, 21 PoTS, 20
      EH and 20 VVS patients. Interoceptive accuracy (IA) was assessed during supine
      rest (9min), isometric exercise (3min), cold pressor (90s) and head up tilt (HUT)
      (9min). RESULTS: In comparison to controls, PoTS, VVS and EH patients reported
      increased symptoms of somatic anxiety but not of social anxiety/self
      consciousness or trauma. Autonomic patients' IA was diminished and consistently
      underestimated even during autonomic arousal compared to controls. Controls and
      EH IA negatively correlated with somatic anxiety/hypervigilance, whereas PoTS and
      VVS IA and somatic anxiety/vigilance positively correlated. CONCLUSIONS:
      Affective symptoms in PoTS, VVS and EH appear to be driven by anxiety and
      vigilance of physical sensations/symptoms, rather than trauma or neurosis.
      Increased somatic vigilance/anxiety in PoTS and VVS may be due to interoception
      being anxiogenic in these cohorts. Diminished interoception may be due to a
      common central dysregulation, as both sudomotor and cardiovascular forms of
      autonomic dysfunction had comparable IA deficits. These findings provide a
      possible therapeutic pathway for psychological symptoms in PoTS, VVS and EH.

PMID- 27865626
TI  - Synergistic combinations of polymyxins.
AB  - The proliferation of extensively drug-resistant Gram-negative pathogens has
      necessitated the therapeutic use of colistin and polymyxin B. However, treatment
      failures with polymyxin monotherapies and the emergence of polymyxin resistance
      have catalysed the search for polymyxin combinations that synergistically kill
      polymyxin-susceptible and -resistant organisms. This mini-review examines recent
      (2011-2016) in vitro and in vivo studies that have attempted to identify
      synergistic polymyxin combinations against Pseudomonas aeruginosa, Klebsiella
      pneumoniae and Acinetobacter baumannii. Clinical evidence for the use of
      combination regimens is also discussed.

PMID- 27865629
TI  - Re: Vasectomy and Prostate Cancer Incidence and Mortality in a Large US Cohort.

PMID- 27865630
TI  - Effects of co-administered dexamethasone and nimesulide on pain, swelling, and
      trismus following third molar surgery: a randomized, triple-blind, controlled
      clinical trial.
AB  - This study aimed to determine the effect of the co-administration of
      dexamethasone 8mg and nimesulide 100mg given 1h before mandibular third molar
      surgery. A prospective, randomized, triple-blind, split-mouth clinical trial was
      developed at the study institution in Pernambuco, Brazil. A pilot study was first
      performed (95% confidence interval, 80% test power, and 5% error), and a sample
      of 40 patients aged between 18 and 40 years was selected. The patients were
      randomized and divided into two groups: dexamethasone+placebo and
      dexamethasone+nimesulide. The following parameters were evaluated: pain (visual
      analogue scale), total number of rescue analgesics taken, time taken to first
      rescue analgesic consumption, oedema, trismus, and patient satisfaction. The
      paired t-test and the Wilcoxon test were used to compare means. Statistically
      significant differences were found between the groups in pain values at 2, 4, and
      12h postoperative, and in the total number of rescue analgesics and time taken to
      first rescue analgesic ingestion (P<0.05), with results in favour of
      dexamethasone+nimesulide administration. Oedema and trismus were similar in the
      two treatment groups and decreased over time postoperatively. The co
      administration of dexamethasone and nimesulide reduces pain intensity and the
      need for rescue medication after third molar surgery.

PMID- 27865631
TI  - The influence of cortical bone perforation on guided bone regeneration in humans.
AB  - The purpose of this study was to evaluate the effect of cortical bone perforation
      on angiogenesis and osteogenesis of the augmented ridge in guided bone
      regeneration. Eighteen patients who had osseous defects in the mandible were
      selected. In the test group (n=9), alveolar cortical bone in the area of
      regeneration was perforated. No decortication was performed in the control group
      (n=9). Subsequently, defects were augmented by guided bone regeneration using
      resorbable membrane and bovine bone. After a healing period of 7 months, trephine
      cores were harvested for histological and histomorphometric analysis of the
      grafted areas. Histomorphometry demonstrated that the amount of newly formed bone
      in the test group (27.8%) was greater than that in the control group (25.3%), but
      the difference was not statistically significant (P=0.13). However, the mean
      number of microvessels in the test group was significantly higher than that in
      the control group (P=0.01). This study found that cortical bone perforation
      favourably affects the amount of new bone formation in the grafted sites after 7
      months of healing. Cortical bone perforation significantly increase number of new
      vessels (angiogenesis) of the regenerated bone. Further randomized clinical
      trials are required to confirm these results.

PMID- 27865632
TI  - Detection of Mycobacterium avium subsp. paratuberculosis in bovine milk from the
      state of Pernambuco, Brazil.
AB  - The aim of this study was to detect the IS900 region of Mycobacterium avium
      subsp. paratuberculosis (MAP) in bovine milk samples using real-time polymerase
      chain reaction (qPCR) and conventional PCR, and to study the agreement between
      these tests. A total of 121 bovine milk samples were collected from herds
      considered positive for MAP, from the State of Pernambuco, Brazil. MAP DNA was
      detected in 20 samples (16.5%) using conventional PCR and in 34 samples (28.1%)
      using qPCR. MAP DNA was detected in all of the 6 animal farms studied. Moderate
      agreement was found between qPCR and conventional PCR results, where the
      sensitivity and specificity of conventional PCR in relation to qPCR were 50% and
      96.6%, respectively. Thus, the IS900 region of MAP was found in bovine milk
      samples from the State of Pernambuco. To the best of our knowledge, this is the
      first report of MAP DNA found in bovine milk in Northeast Brazil. We also
      demonstrated the qPCR technique is more sensitive than conventional PCR with
      respect to detection of MAP in milk samples.

PMID- 27865633
TI  - Celebration of 60th anniversary of Brazilian Society for Microbiology.

PMID- 27865634
TI  - Molecular epidemiology and spatiotemporal analysis of hospital-acquired
      Acinetobacter baumannii infection in a tertiary care hospital in southern
      Thailand.
AB  - BACKGROUND: Acinetobacter baumannii is a major hospital-acquired pathogen in
      Thailand that has a negative effect on patient survival. The nature of its
      transmission is poorly understood. AIM: To investigate the genotypic and
      spatiotemporal pattern of A. baumannii infection at a hospital in Thailand.
      METHODS: The medical records of patients infected with A. baumannii at an 800-bed
      tertiary care hospital in southern Thailand between January 2010 and December
      2011 were reviewed retrospectively. A. baumannii was identified at the
      genomospecies level. Carbapenemase genes were identified among carbapenem
      resistant isolates associated with A. baumannii infection. A spatiotemporal
      analysis was performed by admission ward, time of infection and pulsed-field gel
      electrophoresis (PFGE) groups of A. baumannii. RESULTS: Nine PFGE groups were
      identified among the 197 A. baumannii infections. All A. baumannii isolates were
      assigned to International Clonal Lineage II. blaOXA-23 was the most prevalent
      carbapenemase gene. Outbreaks were observed mainly in respiratory and intensive
      care units. The association between PFGE group and hospital unit was significant.
      Spatiotemporal analysis identified 20 clusters of single PFGE group infections.
      Approximately half of the clusters involved multiple hospital units
      simultaneously. CONCLUSIONS: A. baumannii transmitted both within and between
      hospital wards. Better understanding and control of the transmission of A.
      baumannii are needed.

PMID- 27865635
TI  - [How I do... to see the sliding sign by transvaginal ultrasonography?]

PMID- 27865636
TI  - Transcaval embolization of a type I gutter endoleak after three-vessel chimney
      endovascular aneurysm repair.
AB  - Chimney endovascular aneurysm repair provides an endovascular treatment for
      complex aortic aneurysms. However, type I gutter endoleaks can complicate this
      approach and prevent full aneurysm exclusion. Treatment of these leaks can be
      challenging. We report successful embolization of a type I gutter endoleak after
      (chimney endovascular aneurysm repair) via a transcaval approach.

PMID- 27865637
TI  - Increased risk of mortality after lower extremity bypass in individuals with
      acute kidney injury in the Vascular Quality Initiative.
AB  - OBJECTIVE: The development of acute kidney injury (AKI) and its effect on
      prognosis after lower extremity bypass (LEB) surgery have not been well
      described. We determined risk factors associated with AKI in patients undergoing
      infrainguinal LEB surgery and whether individuals with AKI are at increased risk
      for cardiovascular events and mortality. METHODS: Data for 12,907 operations
      entered in the Vascular Quality Initiative (VQI) registry from January 2012
      through April 2015 were retrospectively reviewed. Procedures performed on
      patients not on dialysis before the surgery with perioperative assessments of
      renal function were eligible for the study. AKI was defined as a postoperative
      increase in serum creatinine >=0.5 mg/dL or new dialysis requirement. Logistic
      regression was performed to determine the effect of AKI on the risk of in
      hospital cardiovascular events, including myocardial infarction, stroke,
      congestive heart failure, or arrhythmias, and mortality. Cox proportional hazards
      regression was performed to determine the risk of long-term mortality (median
      follow-up of 11.5 months). RESULTS: AKI developed after 507 (4%) of the 12,907
      operations performed in 11,859 patients. After adjustment for demographic,
      clinical, and perioperative variables, AKI was associated with an increased risk
      of in-hospital cardiovascular events (odds ratio, 2.50; 95% confidence interval
      [CI], 1.91-3.28) and in-hospital mortality (odds ratio, 6.96; 95% CI, 3.94
      12.31). Risk of mortality persisted over the course of follow-up (hazard ratio,
      1.98; 95% CI, 1.58-2.47). CONCLUSIONS: AKI after LEB is associated with an
      increased risk of cardiovascular events and all-cause mortality. Further study
      should evaluate whether preoperative interventions before LEB can be effectively
      applied for at-risk patients to reduce the incidence of AKI and its associated
      morbidity and mortality.

PMID- 27865638
TI  - Incidence and clinical outcomes of the slow-flow phenomenon after infrapopliteal
      balloon angioplasty.
AB  - OBJECTIVE: This study investigated the incidence and clinical relevance of the
      slow-flow phenomenon after infrapopliteal balloon angioplasty. METHODS: This
      retrospective, single-center study included 161 consecutive patients with
      critical limb ischemia (173 limbs) who underwent endovascular treatment for
      infrapopliteal lesions between January 2012 and May 2015. The overall technical
      success rate was 88%. Of these lesions, 30 limbs presented with slow flow after
      angioplasty. RESULTS: Total occlusion (90% vs 63%; P < .01) and severe
      calcification (43% vs 8%; P < .01) were more common in the slow-flow group.
      Kaplan-Meier curve analysis revealed that freedom from major amputation (60% vs
      86%; log-rank, P < .01) and wound healing at 2 years (77% vs 91%; log-rank, P =
      .03) were significantly less common in the slow-flow group. Univariate Cox
      proportional hazard analysis identified Rutherford class 6 (hazard ratio [HR],
      6.4; 95% confidence interval [CI], 2.8-15.8; P < .01), the slow-flow phenomenon
      (HR, 3.9; 95% CI, 1.6-8.9; P < .01), and hemodialysis (HR, 3.2; 95% CI, 1.2-11.1;
      P = .02) as independent predictors of major amputation and Rutherford class 6
      (HR, 0.3; 95% CI, 0.2-0.6; P < .01), the slow-flow phenomenon (HR, 0.5; 95% CI,
      0.3-0.9; P = .02), and pedal arch (HR, 1.6; 95% CI, 1.0-2.5; P = .04) as
      predictors of wound healing. CONCLUSIONS: The slow-flow phenomenon after
      infrapopliteal balloon angioplasty occurred in 18.6% of limbs. This phenomenon
      may result in poor outcomes.

PMID- 27865639
TI  - A network meta-analysis of randomized controlled trials comparing treatment
      modalities for de novo superficial femoral artery occlusive lesions.
AB  - BACKGROUND: Treatment of superficial femoral artery (SFA) lesions remains
      challenging. We conducted a network meta-analysis of randomized controlled trials
      aiming to explore the efficacy of treatment modalities for SFA "de novo" lesions.
      METHODS: Eleven treatments for SFA occlusive disease were recognized. We used
      primary patency and binary restenosis at 12-month follow-up as proxies of
      efficacy for the treatment of SFA lesions. RESULTS: A total of 33 studies (66
      study arms; 4659 patients) were deemed eligible. In terms of primary patency,
      odds ratios (ORs) with 95% confidence intervals (CIs) were statistically
      significantly higher in drug-eluting stent (DES; OR, 10.05; 95% CI, 3.22-31.39),
      femoropopliteal bypass surgery (BPS; OR, 7.15; 95% CI, 2.27-22.51), covered stent
      (CS; OR, 3.56; 95% CI, 1.33-9.53), and nitinol stent (NS; OR, 2.83; 95% CI, 1.42
      5.51) compared with balloon angioplasty (BA). The rank order from higher to lower
      primary patency in the multidimensional scaling was DES, BPS, NS, CS, drug-coated
      balloon, percutaneous transluminal angioplasty with brachytherapy, stainless
      steel stent, cryoplasty (CR), and BA. Combination therapy of NS with CR and drug
      coated balloon were the two most effective treatments, followed by NS, CS,
      percutaneous transluminal angioplasty with brachytherapy, cutting balloon,
      stainless steel stent, BA, and CR in terms of multidimensional scaling values for
      binary restenosis. CONCLUSIONS: DES has shown encouraging results in terms of
      primary patency for SFA lesions, whereas BPS still maintains its role as a
      principal intervention. On the contrary, BA and CR appear to be less effective
      treatment options.

PMID- 27865640
TI  - Technicians and other pharmacy support workforce cadres working with pharmacists:
      Singapore case study.

PMID- 27865641
TI  - Canadian Cardiovascular Society Guidelines on Perioperative Cardiac Risk
      Assessment and Management for Patients Who Undergo Noncardiac Surgery.
AB  - The Canadian Cardiovascular Society Guidelines Committee and key Canadian opinion
      leaders believed there was a need for up to date guidelines that used the Grading
      of Recommendations Assessment, Development, and Evaluation (GRADE) system of
      evidence assessment for patients who undergo noncardiac surgery. Strong
      recommendations included: 1) measuring brain natriuretic peptide (BNP) or N
      terminal fragment of proBNP (NT-proBNP) before surgery to enhance perioperative
      cardiac risk estimation in patients who are 65 years of age or older, are 45-64
      years of age with significant cardiovascular disease, or have a Revised Cardiac
      Risk Index score >= 1; 2) against performing preoperative resting
      echocardiography, coronary computed tomography angiography, exercise or
      cardiopulmonary exercise testing, or pharmacological stress echocardiography or
      radionuclide imaging to enhance perioperative cardiac risk estimation; 3) against
      the initiation or continuation of acetylsalicylic acid for the prevention of
      perioperative cardiac events, except in patients with a recent coronary artery
      stent or who will undergo carotid endarterectomy; 4) against alpha2 agonist or
      beta-blocker initiation within 24 hours before surgery; 5) withholding
      angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker
      starting 24 hours before surgery; 6) facilitating smoking cessation before
      surgery; 7) measuring daily troponin for 48 to 72 hours after surgery in patients
      with an elevated NT-proBNP/BNP measurement before surgery or if there is no NT
      proBNP/BNP measurement before surgery, in those who have a Revised Cardiac Risk
      Index score >=1, age 45-64 years with significant cardiovascular disease, or age
      65 years or older; and 8) initiating of long-term acetylsalicylic acid and statin
      therapy in patients who suffer myocardial injury/infarction after surgery.

PMID- 27865642
TI  - Attention to Physical Activity-Equivalent Calorie Information on Nutrition Facts
      Labels: An Eye-Tracking Investigation.
AB  - OBJECTIVE: Investigate attention to Nutrition Facts Labels (NFLs) with numeric
      only vs both numeric and activity-equivalent calorie information, and attitudes
      toward activity-equivalent calories. DESIGN: An eye-tracking camera monitored
      participants' viewing of NFLs for 64 packaged foods with either standard NFLs or
      modified NFLs. Participants self-reported demographic information and diet
      related attitudes and behaviors. SETTING: Participants came to the Behavioral
      Medicine Lab at Colorado State University in spring, 2015. PARTICIPANTS: The
      researchers randomized 234 participants to view NFLs with numeric calorie
      information only (n = 108) or numeric and activity-equivalent calorie information
      (n = 126). MAIN OUTCOME MEASURE(S): Attention to and attitudes about activity
      equivalent calorie information. ANALYSIS: Differences by experimental condition
      and weight loss intention (overall and within experimental condition) were
      assessed using t tests and Pearson's chi-square tests of independence. RESULTS:
      Overall, participants viewed numeric calorie information on 20% of NFLs for 249
      ms. Participants in the modified NFL condition viewed activity-equivalent
      information on 17% of NFLs for 231 ms. Most participants indicated that activity
      equivalent calorie information would help them decide whether to eat a food (69%)
      and that they preferred both numeric and activity-equivalent calorie information
      on NFLs (70%). CONCLUSIONS AND IMPLICATIONS: Participants used activity
      equivalent calorie information on NFLs and found this information helpful for
      making food decisions.

PMID- 27865643
TI  - Identification and characterization of an enzyme involved in the biosynthesis of
      the 4-hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone in yeast.
AB  - 4-Hydroxy-2(or 5)-ethyl-5(or 2)-methyl-3(2H)-furanone (HEMF) is considered a key
      flavor compound in soy sauce. The compound has a caramel-like aroma and several
      important physiological activities, such as strong antioxidant activity. Here, we
      report the identification and characterization of an enzyme involved in the
      biosynthesis of HEMF in yeast. We fractionated yeast cell-free extract from
      Saccharomyces cerevisiae using column chromatography and partially purified a
      fraction with HEMF-forming activity. Peptide mass fingerprinting analysis showed
      that the partially purified fraction contains aldehyde reductase encoded by
      YNL134C. This reductase shares low sequence identity with enone oxidoreductase,
      which is responsible for the formation of 4-hydroxy-2,5-dimethyl-3(2H)-furanone
      (HDMF) and HEMF in plants. YNL134C was expressed heterologously in Escherichia
      coli, and the purified protein catalyzed the formation of HEMF from the mixture
      of Maillard reaction products, acetaldehydes, and NADPH. Multicopy expression in
      S. cerevisiae resulted in increased HEMF productivity, and gene knockout of
      YNL134C in S. cerevisiae resulted in decreased HEMF productivity. These data
      suggest that the translation product of YNL134C is the HEMF-producing enzyme in
      yeast. Detailed analyses of an intermediate in the enzymatic reaction mixture
      revealed that HEMF is synthesized from (2E)-2-ethylidene-4-hydroxy-5-methyl-3(2H)
      furanone, which formed via Knoevenagel condensation between the acetaldehyde and
      4-hydroxy-5-methyl-3(2H)-furanone derived from the Maillard reaction based on
      ribose and glycine, by YNL134Cp in an NADPH dependent manner. Overall, this study
      shed light on the molecular basis for the improvement of soy sauce flavor and the
      biotechnological production of HEMF.

PMID- 27865646
TI  - Long-term oxygen in COPD.

PMID- 27865644
TI  - Bioactivity of topologically confined gramicidin A dimers.
AB  - The d-/l-peptide gramicidin A (gA) is well known as a pivotal ion channel model
      and shows a broad spectrum of bioactivities such as antibiosis, antimalarial
      activity, as well as hemolysis. We applied inter-chain disulfide bonds to
      constrain the conformational freedom of gA into parallel and antiparallel dimeric
      topologies. Albeit the constructs were not found to be monoconformational, CD-
      and IR-spectroscopic studies suggested that this strategy indeed restricted the
      conformational space of the d-/l-peptide construct, and that beta-helical
      secondary structures prevail. Correlative testing of gA dimers in antimicrobial,
      antimalarial, and ion conduction assays suggested that the tail-to-tail
      antiparallel single stranded beta6.3 helix dominantly mediates the bioactivity of
      gA. Other conformers are unlikely to contribute to these activities. From these
      investigations, only weakly ion conducting gA dimers were identified that
      retained nM antimalarial activity.

PMID- 27865647
TI  - UK Government chokes on air pollution crisis.

PMID- 27865645
TI  - Discovery of SMP-304, a novel benzylpiperidine derivative with serotonin
      transporter inhibitory activity and 5-HT1A weak partial agonistic activity
      showing the antidepressant-like effect.
AB  - We report the discovery of a novel benzylpiperidine derivative with serotonin
      transporter (SERT) inhibitory activity and 5-HT1A receptor weak partial agonistic
      activity showing the antidepressant-like effect. The 3-methoxyphenyl group and
      the phenethyl group of compound 1, which has weak SERT binding activity, but
      potent 5-HT1A binding activity, were optimized, leading to compound 35 with
      potent and balanced dual SERT and 5-HT1A binding activity, but also potent CYP2D6
      inhibitory activity. Replacement of the methoxy group in the left part of
      compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy
      ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP
      304 with serotonin uptake inhibitory activity and 5-HT1A weak partial agonistic
      activity, which could work as a 5-HT1A antagonist, displayed faster onset of
      antidepressant-like effect than a representative SSRI paroxetine in an animal
      model.

PMID- 27865649
TI  - Extracellular vesicles in transfusion-related immunomodulation and the role of
      blood component manufacturing.
AB  - There is an emerging interest in the risks posed by the ability of blood
      transfusion to modulate the immune system of recipients. Observational trials
      suggest that RBC transfusions may be associated with increased morbidity and
      mortality, however studies demonstrating the deleterious consequences of
      transfusion-related immunomodulation have had conflicting results. Efforts to
      understand the biological mechanisms responsible for TRIM are under way, and are
      focusing on the role that the extracellular vesicles (EVs) that accumulate in a
      red cell concentrate (RCC) during storage may play. EVs are heterogeneous
      submicron-sized vesicles that vary in size, composition and surface biomarkers.
      The biophysical and biochemical parameters of EVs reflect their mechanism of
      formation and cell sources. RCCs have been shown to contain a mixed population of
      EVs and not all EVs in RCC are solely from the constituent RBCs. The
      concentration of the different EVs (the RBC EVs and the non-RBC EVs), their
      composition, as well as their effects on the quality of the blood product vary
      depending on the manufacturing methods used to produce the RCC units. This
      article will review current evidence of the role of extracellular vesicles in
      transfusion-related immunomodulation and will discuss the impact that different
      methods used to collect, manufacture and store blood have on the composition and
      characteristics of EVs in RCCs.

PMID- 27865648
TI  - Related factors with extravasation of non-cytostatic agents in peripheral vein
      catheters.
AB  - OBJECTIVE: To know the independent variables related to the occurrence of
      extravasation in patients with peripheral vein catheters (PVC). MATERIAL AND
      METHOD: Retrospective study carried out in 6 longitudinal cuts between July 2013
      an January 2014. A total of 1,442 PVC were reviewed, of which 730 met the
      inclusion criteria, and were divided into 2 groups: extravasation and not
      extravasation, with 365 cases each. The variables of age, gender, admission unit,
      catheter gauge, insertion site, previous insertion into the same limb, hospital
      unit where the insertion took place, communication difficulties, personal health
      history and analyzed parenterally drug administered were considered. RESULTS:
      Risk factors to develop extravasation were: female gender, with previous
      insertion in the same limb, <72h PVC of insertion, communication difficulties,
      personal health history of neoplasia and KCl, gentamicin or beta lactam
      treatment. CONCLUSIONS: Our study allows to know the variables that are related
      to the emergence of extravasations in patients with non-cancer treatments
      (gender, medical service of admission, catheter gauge, elapsed time since the
      insertion, patient communication difficulties, personal health history, and
      intravenous treatments), as well as the factors that may be considered
      protective.

PMID- 27865650
TI  - Economic assessment of integrated cancer and cardiovascular registries: The
      Barbados experience.
AB  - BACKGROUND: This report describes the resources required to support the
      integrated approach of the Barbados National Registry for Chronic Non
      communicable Diseases (BNR) to non-communicable disease (NCD) case registration,
      and to identify differences in cost for collecting and maintaining information on
      cancer and cardiovascular disease (CVD) case registration. METHODS: We used the
      modified Centers for Disease Control and Prevention's International Registry
      Costing Tool to collect data from the CVD and cancer registries. We used cancer
      and CVD cost data for the annual period April 2014 through March 2015 to estimate
      the total cost and cost per case. We used prospectively collected average annual
      CVD cases, and for cancer cases we assumed 2 or 3 years are needed for
      retrospective data collection. RESULTS: The Ministry of Health provided 56% of
      the resources for the registries. Labor accounted for over 70% of both
      registries' budgets, while management and administration, along with data
      collection and analysis, incurred the highest costs per case. Total variable cost
      activities related to data collection and analysis were higher for the CVD
      component (US$131,297) than the cancer component (US$58,917). The CVD cost per
      case (US$489) was in between the cancer 2-year (US$382) and the cancer 3-year
      (US$573) cost-per-case estimates. CONCLUSION: These findings indicate that there
      are substantial fixed costs related to management and administration of NCD
      registries. All registries need management and administration support. When
      registries are combined, management and administration costs can be shared. We
      project that registries that can share fixed-cost infrastructure are likely to
      incur a lower total cost per case.

PMID- 27865651
TI  - Beyond Supermarkets: Food Outlet Location Selection in Four U.S. Cities Over
      Time.
AB  - INTRODUCTION: Understanding what influences where food outlets locate is
      important for mitigating disparities in access to healthy food outlets. However,
      few studies have examined how neighborhood characteristics influence the
      neighborhood food environment over time, and whether these relationships differ
      by neighborhood-level income. METHODS: Neighborhood-level data from four U.S.
      cities (Birmingham, AL; Chicago, IL; Minneapolis, MN; Oakland, CA) from 1986,
      1993, 1996, 2001, 2006, and 2011 were used with two-step econometric models to
      estimate longitudinal associations between neighborhood-level characteristics (z
      scores) and the log-transformed count/km2 (density) of food outlets within real
      estate-derived neighborhoods. Associations were examined with lagged neighborhood
      level sociodemographics and lagged density of food outlets, with interaction
      terms for neighborhood-level income. Data were analyzed in 2016. RESULTS:
      Neighborhood-level income at earlier years was negatively associated with the
      current density of convenience stores (beta= -0.27, 95% CI= -0.16, -0.38,
      p<0.001). The percentage of neighborhood white population was negatively
      associated with fast food restaurant density in low-income neighborhoods (10th
      percentile of income: beta= -0.17, 95% CI= -0.34, -0.002, p=0.05), and the
      density of smaller grocery stores across all income levels (beta= -0.27, 95% CI= 
      0.45, -0.09, p=0.003). There was a lack of policy-relevant associations between
      the pre-existing food environment and the current density of food outlet types,
      including supermarkets. CONCLUSIONS: Socioeconomically disadvantaged and minority
      populations may attract "unhealthy" food outlets over time. To support equal
      access to healthy food outlets, the availability of "less healthy" food outlets
      types may be relatively more important than the potential lack of supermarkets or
      full-service restaurants.

PMID- 27865652
TI  - Development and Evaluation of a Short Adverse Childhood Experiences Measure.
AB  - INTRODUCTION: Clinicians require tools to rapidly identify individuals with
      significant childhood adversity as part of routine primary care. The goal of this
      study was to shorten the 11-item Behavioral Risk Factor Surveillance System
      Adverse Childhood Experiences (ACEs) measure and evaluate the feasibility and
      validity of this shortened measure as a screener to identify adults who have
      experienced significant childhood adversity. METHODS: Statistical analysis was
      conducted in 2015. ACE item responses obtained from 2011-2012 Behavioral Risk
      Factor Surveillance System data were combined to form a sample of 71,413 adults
      aged >=18 years. The 11-item Behavioral Risk Factor Surveillance System ACE
      measure was subsequently reduced to a two-item screener by maintaining the two
      dimensions of abuse and household stressors and selecting the most prevalent item
      within each dimension. RESULTS: The screener included household alcohol and
      childhood emotional abuse items. Overall, 42% of respondents and at least 75% of
      the individuals with four or more ACEs endorsed one or both of these experiences.
      Using the 11-item ACE measure as the standard, a cut off of one or more ACEs
      yielded a sensitivity of 99%, but specificity was low (66%). Specificity improved
      to 94% when using a cut off of two ACEs, but sensitivity diminished (70%). There
      was no substantive difference between the 11-and two-item ACE measures in their
      strength of association with an array of health outcomes. CONCLUSIONS: A two-item
      ACE screener appropriate for rapid identification of adults who have experienced
      significant childhood adversity was developed.

PMID- 27865654
TI  - Surgery for recurrent ovarian cancer: Options and limits.
AB  - Cytoreductive surgery is the backbone of the multimodal therapy in primary
      ovarian cancer patients. Despite the effect of various tumor biological factors
      such as grading and histological subtype, the surgical outcome is the most
      important prognostic factor for both progression free- and overall survival. In
      contrast, the management of recurrent situation has long remained a subject of an
      emotional international discussion. To date, only few prospective studies have
      focused on the effect of surgery in relapsed ovarian cancer. The available
      retrospective data associate complete cytoreduction with prognosis improvement.
      However, the selection of patients eligible for surgery in recurrent situation is
      the essential issue. The establishment of predictive factors for complete tumor
      resection and defining the patient group with recurrent disease who might profit
      from this approach are crucial. The available predictors of complete resection
      depend on the results of primary surgery and the current patient's situation.
      Women who underwent primary complete cytoreduction are in good performance
      status, and those who have only minimal ascites volume (less than 500 ml) in the
      recurrent situation have 76% likelihood of undergoing complete resection and
      survival prolongation. Moreover, the complete cytoreduction in the tertiary
      cytoreductive approach has been evaluated and showed a potential positive
      influence on patients' survival. This review concentrates on the recent data and
      highlights the need of further randomized trials to develop and incorporate
      operative standards in recurrent ovarian cancer.

PMID- 27865653
TI  - Evaluation of School-Based Dental Sealant Programs: An Updated Community Guide
      Systematic Economic Review.
AB  - CONTEXT: A recently updated Community Guide systematic review of the
      effectiveness of school sealant programs (SSPs) still found strong evidence that
      SSPs reduced dental caries among schoolchildren. This follow-up systematic review
      updates SSP cost and benefit information from the original 2002 review. EVIDENCE
      ACQUISITION: Using Community Guide economic review methods, the authors searched
      the literature from January 2000 to November 20, 2014. The final body of evidence
      included 14 studies-ten from the current search and four with cost information
      from the 2002 review. Nine studies had information on SSP costs; six on sealant
      benefit (averted treatment costs and productivity losses); four on SSP net cost
      (cost minus benefit); and three on net cost to Medicaid of clinically delivered
      sealants. The authors imputed productivity losses and discounted costs/outcomes
      when this information was missing. The analysis, conducted in 2015, reported all
      values in 2014 U.S. dollars. EVIDENCE SYNTHESIS: The median one-time SSP cost per
      tooth sealed was $11.64. Labor accounted for two thirds of costs, and time to
      provide sealants was a major cost driver. The median annual economic benefit was
      $6.29, suggesting that over 4 years the SSP benefit ($23.37 at a 3% discount
      rate) would exceed costs by $11.73 per sealed tooth. In addition, two of four
      economic models and all three analyses of Medicaid claims data found that SSP
      benefit to society exceeded SSP cost. CONCLUSIONS: Recent evidence indicates the
      benefits of SSPs exceed their costs when SSPs target schools attended by a large
      number of high-risk children.

PMID- 27865655
TI  - Corrigendum to "Ten-year improvement of insulin resistance and growth with
      recombinant human insulin-like growth factor 1 in a patient with insulin receptor
      mutations resulting in leprechaunism" [Diabetes Metab. 41 (2015) 331-337].

PMID- 27865657
TI  - Cranial adaptations for feeding on snails in species of Sibynomorphus
      (Dipsadidae: Dipsadinae).
AB  - Neotropical "goo-eating" dipsadine snakes display a set of morphological and
      histo-chemical adaptations linked to the capture of their soft-bodied, viscous
      invertebrate prey. Within this group, species from the genus Sibynomorphus feed
      chiefly on snails and slugs. Here, we analyzed a series of skull and mandible
      characters in S. mikanii, S. neuwiedi and S. turgidus using geometric
      morphometrics, with the aim of assessing morphological adaptations related to
      slug- and snail-feeding in that genus. We further compared the results with
      Leptodeira annulata, a species that feeds on vertebrates. To evaluate shape
      differences of the skull and mandible between species we performed a multivariate
      analysis of variance and a linear discriminant analysis. Our results show that
      the narrow, elongate skull in S. mikanii may help with slug ingestion, while
      asymmetry in teeth number and mandibular shape in S. neuwiedi and S. turgidus are
      likely related to snail feeding.

PMID- 27865656
TI  - Nut consumption is associated with lower incidence of type 2 diabetes: The Tehran
      Lipid and Glucose Study.
AB  - AIM: Nuts are rich in unsaturated fatty acids as well as other bioactive
      constituents. The present study investigated the association between nut
      consumption and the incidence of type 2 diabetes mellitus (T2DM) in a Middle
      Eastern population. METHODS: The study was conducted within the framework of the
      Tehran Lipid and Glucose Study (TLGS), in which 1984 participants (920 men and
      1064 women) free of DM, aged>=20 years, were followed from phase III (2005-2008)
      to phase V (2011-2014). Dietary data were obtained from valid and reliable food
      frequency questionnaires at baseline. Using multiple logistic regression, odds
      ratios (ORs) and 95% confidence intervals (CIs) were calculated, with adjustments
      for age, gender, BMI, serum cholesterol and triglycerides, smoking and energy
      intake. RESULTS: Study participants' means+/-SD of age and of BMI were 40.1+/
      13.1 years and 27.0+/-4.8kg/m2, respectively. The median+/-SE of their total
      daily consumption of nuts was 1.19+/-0.11 servings. After 6.2+/-0.7 years of
      follow-up, 150 cases of T2DM were confirmed. On comparing those who consumed >=4
      servings/week with those who consumed <1 serving/week, the age-/energy-adjusted
      OR of incident T2DM for total nut consumption was 0.64 (95% CI: 0.36-1.12; P for
      trend = 0.03). In a fully adjusted model, nut consumption was associated with a
      lower risk of T2DM, and the ORs (95% CIs) of risk for those consuming 2-3.99 and
      >=4 servings/week of nuts were 0.51 (0.26-0.97) and 0.47 (0.25-0.90),
      respectively, compared with those consuming <1 serving/week (P<0.001 for trend).
      CONCLUSION: Our findings suggest that consuming >=4 servings/week of nuts reduced
      the risk of T2DM compared with <1 serving/week.

PMID- 27865658
TI  - Characterization of particulate-phase polycyclic aromatic hydrocarbons emitted
      from incense burning and their bioreactivity in RAW264.7 macrophage.
AB  - This study investigated the effects of particle-bound polycyclic aromatic
      hydrocarbons (PAHs) produced from burning three incense types on and their
      bioreactivity in the RAW 264.7 murine macrophage cell line. Gas
      chromatography/mass spectrometry was used to determine the levels of 16
      identified PAHs. Macrophages were exposed to incense particle extracts at
      concentrations of 0, 3.125, 6.25, 12.5, 25, 50, and 100 MUg/mL for 24 h. After
      exposure, cell viability and nitric oxide (NO) and inflammatory mediator [tumor
      necrosis factor (TNF)-alpha] production of the cells were examined. The mean
      atomic hydrogen (H) to carbon (C) ratios in the environmentally friendly,
      binchotan charcoal, and lao shan incenses were 0.69, 1.13, and 1.71,
      respectively. PAH and total toxic equivalent (TEQ) mass fraction in the incenses
      ranged from 137.84 to 231.00 and 6.73-26.30 pg/MUg, respectively. The exposure of
      RAW 264.7 macrophages to incense particles significantly increased TNF-alpha and
      NO production and reduced cell viability. The cells treated with particles
      collected from smoldering the environmentally friendly incense produced more NO
      and TNF-alpha compared to other incenses. Additionally, the TEQ of fluoranthene
      (FL), pyrene (Pyr), benzo[a]anthracene (BaA), chrysene (Chr),
      benzo[b]fluoranthene (BbF), benzo[k]fluoranthene (BkF), benzo[a]pyrene (BaP),
      indeno[1,2,3-cd]pyrene (INP), dibenz[a,h]anthracene (DBA), and
      benzo[g,h,i]perylene [B(ghi)P] had a significant correlation (R2 = 0.64-0.98, P <
      0.05) with NO and TNF-alpha production. The current findings indicate that
      incense particle-bound PAHs are biologically active and that burning an incense
      with a lower H/C ratio caused higher bioreactivity. The stimulatory effect of PAH
      containing particles on molecular mechanisms of inflammation are critical for
      future study.

PMID- 27865659
TI  - Using long-term air monitoring of semi-volatile organic compounds to evaluate the
      uncertainty in polyurethane-disk passive sampler-derived air concentrations.
AB  - Much effort has been made to standardise sampling procedures, laboratory
      analysis, data analysis, etc. for semi volatile organic contaminants (SVOCs). Yet
      there are some unresolved issues in regards to comparing measurements from one of
      the most commonly used passive samplers (PAS), the polyurethane foam (PUF) disk
      PAS (PUF-PAS), between monitoring networks or different studies. One such issue
      is that there is no universal means to derive a sampling rate (Rs) or to
      calculate air concentrations (Cair) from PUF-PAS measurements for SVOCs. Cair was
      calculated from PUF-PAS measurements from a long-term monitoring program at a
      site in central Europe applying current understanding of passive sampling theory
      coupled with a consideration for the sampling of particle associated compounds.
      Cair were assessed against concurrent active air sampler (AAS) measurements. Use
      of "site-based/sampler-specific" variables: Rs, calculated using a site
      calibration, provided similar results for most gas-phase SVOCs to air
      concentrations derived using "default" values (commonly accepted Rs). Individual
      monthly PUF-PAS-derived air concentrations for the majority of the target
      compounds were significantly different (Wilcoxon signed-rank (WSR) test; p <
      0.05) to AAS regardless of the input values (site/sampler based or default) used
      to calculate them. However, annual average PUF-PAS-derived air concentrations
      were within the same order of magnitude as AAS measurements except for the
      particle-phase polycyclic aromatic hydrocarbons (PAHs). Underestimation of PUF
      derived air concentrations for particle-phase PAHs was attributed to a potential
      overestimation of the particle infiltration into the PUF-PAS chamber and
      underestimation of the particle bound fraction of PAHs.

PMID- 27865661
TI  - The association between subjective health status and 14-year mortality in post
      PCI patients.
AB  - BACKGROUND: Poor subjective health status significantly predicted short-term
      mortality in patients with coronary artery disease (CAD). However, the relation
      between subjective health status and long-term mortality remains limited in
      patients treated with PCI. The aim of this study is to investigate the
      association between subjective health status and 14-year mortality in patients
      treated with percutaneous coronary intervention (PCI). METHODS: A consecutive
      cohort with 1111 patients treated for CAD who completed the SF-36 questionnaire
      was included between 2001 and 2002 as part of the RESEARCH registry. RESULTS:
      After adjustment, physical functioning (HR: 1.96; 95% CI: 1.59-2.43), social
      functioning (HR: 1.53; 95% CI: 1.24-1.88), role limitations due to physical
      functioning (HR: 1.75; 95% CI: 1.41-2.16), role limitations due to emotional
      functioning (HR: 1.34; 95%CI: 1.08-1.67), mental health (HR: 1.52; 95% CI: 1.24
      1.88), vitality (HR: 1.66; 95% CI: 1.35-2.03), bodily pain (HR: 1.63; 95% CI:
      1.32-2.02) and general health (HR: 1.82; 95% CI: 1.49-2.23) were all associated
      with an increased risk of 14-year mortality. CONCLUSION: Physical and mental
      subjective health status as measured with the SF-36 appeared to be a strong
      predictor for 14-year mortality in post-PCI patients.

PMID- 27865660
TI  - Vitamin D3 a new drug against Candida albicans.
AB  - OBJECTIVE: In this study, we demonstrate that vitamin D3 had fungicidal activity
      against Candida albicans. MATERIAL AND METHODS: The susceptibility of the yeast
      strain to the vitamin D3 was investigated by the antimicrobial screening using
      modified agar diffusion method, minimum fungistatic concentrations (MFCs) and
      minimum fungicide concentrations (MFCC) of the vitamin D3 were determined by the
      broth dilution method. RESULTS: The antifungal activity indicted that 100MUg/ml
      of vitamin D3 had a power inhibition in the growth of C. albicans with zone of
      inhibition 12.5mm and CMFC and CMFs were 1.58+/-0.0764MUg/ml. CONCLUSION: These
      values indicate that vitamin D3 can be considered to have fungicide activity.
      This antifungal effect may be due to the large lipsolubility of vitamin D3
      changing the integrity of the cell membrane.

PMID- 27865663
TI  - Hyposmolarity may be also associated with worse outcomes in patients with heart
      failure.

PMID- 27865662
TI  - Sex differences in acute myocardial infarction: Is it only the age?
AB  - BACKGROUND: Several studies have shown that, after an acute myocardial
      infarction, women have worse prognosis than males. However, it is not clear if
      female sex is an independent predictor of mortality risk. Our aim was to analyse
      sex influence on the prognosis of these patients. METHODS: Retrospective registry
      of patients with ST segment elevation myocardial infarction (STEMI) from January
      2010 to April 2015. RESULTS: From 1111 patients, 258 (23.2%) were women. Compared
      with men, they presented higher risk profiles with older age (70.1+/-14.4years
      vs. 62.3+/-13.4, P<0.001), more cardiovascular risk factors (except smoking),
      longer time from symptoms onset to hospital arrival (5.2+/-4.1h vs. 4.2+/-3.7),
      higher Killip classification (1.6+/-1.1 vs. 1.4+/-0.8), fewer complete
      revascularizations (175 [67.8%] vs. 662 [77.9%] in men) and higher in-hospital
      mortality (26 [10.1%] vs. 34 [4.0%]); all p values <0.003. At discharge, women
      less frequently received ACE inhibitors (189 [81.1%] vs. 702 [85.8%], p=0.045)
      and presented more major adverse events (death, bleeding, infection, myocardial
      infarction, stent thrombosis or heart failure) during the first month after
      discharge (10.5% vs. 4.5%, p<0.001) and higher long-term mortality (hazard ratio
      [HR] 1.6, 95% CI 1.1-2.2). After adjusting by age, most of the differences
      disappeared, and sex was not an independent factor of in-hospital (odds ratio
      1.71, 95% CI 0.97-2.99) or long-term mortality (HR 1.0, 95% CI 0.7-1.5).
      CONCLUSIONS: In patients with acute STEMI, the association of female sex with
      poor prognosis is mainly explained by age. Sex does not seem to be an independent
      prognostic factor.

PMID- 27865664
TI  - Statin protects the heart against ischemia-reperfusion injury via inhibition of
      the NLRP3 inflammasome.

PMID- 27865665
TI  - Enhanced volatile fatty acid production from excess sludge by combined free
      nitrous acid and rhamnolipid treatment.
AB  - VFA production from excess sludge (ES) was greatly enhanced by a low-cost and
      high-efficient treatment: 0.67mg/L free nitrous acid (FNA) pretreatment combined
      with 0.04g/g TSS rhamnolipid (RL) addition (FNA+RL), which significantly
      shortened fermentation time to 3days and increased VFA production to
      352.26mgCOD/g VSS (5.42 times higher than raw ES). Propionic and acetic acids
      were the two leading components (71.86% of the total VFA). Mechanism
      investigation manifested FNA+RL improved the biodegradability of ES, achieved
      positive synergetic effect on solubilization, hydrolysis and acidification
      efficiencies, and inhibited methanation. Microbial community distribution further
      explained the above phenomena. The bacteria related to polysaccharides/protein
      utilization and VFA generation, including Clostridium, Megasphaera and
      Proteiniborus, were mainly observed in FNA+RL, whereas gas-forming bacteria
      Anaerolineae and acid-consuming bacteria Proteobacteria were assuredly
      suppressed. Besides, Propionibacterineae associated with propionic acid
      generation was exclusively enriched in sole RL and FNA+RL.

PMID- 27865666
TI  - Reducing sugar loss in enzymatic hydrolysis of ethylenediamine pretreated corn
      stover.
AB  - In this study, the effect of ethylenediamine (EDA) on enzymatic hydrolysis with
      different cellulosic substrates and the approaches to reduce sugar loss in
      enzymatic hydrolysis were investigated. During enzymatic hydrolysis, xylose yield
      reduced 21.2%, 18.1% and 13.0% with 7.5mL/L EDA for AFEX pretreated corn stover
      (CS), washed EDA pretreated CS and CS cellulose. FTIR and GPC analysis
      demonstrated EDA reacted with sugar and produced high molecular weight (MW)
      compounds. EDA was prone to react with xylose other than glucose. H2O2 and Na2SO3
      cannot prevent sugar loss in glucose/xylose-EDA mixture, although they inhibited
      the browning and high MW compounds formation. By decreasing temperature to 30
      degrees C, the loss of xylose yield reduced to only 3.8%, 3.6% and 4.2% with
      7.5mL/L EDA in the enzymatic hydrolysis of AFEX pretreated CS, washed EDA
      pretreated CS and CS cellulose.

PMID- 27865667
TI  - Lower urinary tract symptoms in Parkinson's disease: Prevalence, aetiology and
      management.
AB  - Lower urinary tract symptoms (LUTS) are common in Parkinson's disease (PD),
      effecting 27-85% of patients with PD. Irritative symptoms predominate and
      urodynamic studies confirm high prevalence of detrusor overactivity in PD. LUTS
      are present early in PD and are more common in PD than in age matched controls.
      The assessment of LUTS in PD is complicated by coexisting bradykinesia and
      cognitive impairment. Although LUTS become more troublesome as PD progresses it
      remains unclear if LUTS severity correlates with motor symptoms and/or duration
      of PD. The underlying cause of LUTS in PD remains to be fully elucidated. Animal
      and human studies suggest the net effect of the basal ganglia is to supress
      micturition. Although LUTS are a common in PD, few studies have examined the
      assessment and management of LUTS specifically in patients with PD. Pilot studies
      have suggested that bladder training, antimuscarinic drugs and intravesical
      botulinum toxin maybe helpful but these trials have been small and frequently
      lacked a suitable control group making them vulnerable to the placebo effect.
      Furthermore the adverse effects of antimuscarinic drugs on cognitive and
      gastrointestinal function may limit the use of these drugs in PD. In this review
      we summarise the literature describing the prevalence of LUTS in PD, discuss the
      emerging data delineating the underlying pathophysiology of LUTS and examine
      interventions helpful in the management of LUTS in people with PD.

PMID- 27865668
TI  - A small pons as a characteristic finding in Down syndrome: A quantitative MRI
      study.
AB  - BACKGROUND: Down syndrome (DS) is the most common chromosomal aberration, but the
      characteristics of the brainstem component in this condition during childhood
      (from newborn to preteen stages) have not been clarified. OBJECTIVE: To evaluate
      the morphological features of the brainstem in DS on magnetic resonance imaging
      (MRI). MATERIALS AND METHODS: MRIs for 32 children with DS (16 boys and girls
      each; age range, 0-11years) without major brain insults, and 32 age-matched
      controls (16 boys and girls each) were retrospectively analyzed. Height, width,
      and area of the midbrain, pons, and medulla oblongata were measured on sagittal
      T1-weighted images; these were compared in children with DS and age-matched
      controls. The ratios of the brainstem to the size of the posterior fossa (BS/PF
      index) were calculated; these were also compared in the children with DS and the
      control group. RESULTS: The width and area of the midbrain; height, width, area
      of the pons; and area of the medulla oblongata were significantly smaller in
      children with DS than in control children (P<0.05); the area of the pons,
      particularly for the ventral part, showed the largest differences in the mean
      relative differences. The BS/PF indices of the height, width, and area of the
      pons were significantly smaller in children with DS than in the control group
      (P<0.01). However, the BS/PF indices for the midbrain and the medulla oblongata
      did not differ between these two groups. CONCLUSIONS: Children with DS may have
      small brainstems, particularly in the pons; this may be a characteristic
      morphological feature of the brainstem on MRI in childhood including neonates.

PMID- 27865669
TI  - PiN photodiode performance comparison for dosimetry in radiology applications.
AB  - Performance comparison of selected photodiodes for usage as radiation detectors
      for radio-protection is presented. In this study, based on the criteria of
      minimum sensitive area of 5mm2, minimum half angle 60 degrees  and low cost, four
      commercial photodiodes are selected for evaluation: SFH205, SFH206, BPW34, and
      BPX90F. Photodiodes are low cost, small volume and lightweight detectors. As an
      electronic transducer, photodiode detector is an attractive approach for the
      development of low power portable electronic dosimeter for direct-reading real
      time radiation dose measurement. The devices have been studied with respect to
      sensitivity (efficiency) in X-rays and gamma rays detection, repeatability and
      linearity in air kerma.

PMID- 27865670
TI  - Radiation damage to neuronal cells: Simulating the energy deposition and water
      radiolysis in a small neural network.
AB  - Radiation damage to the central nervous system (CNS) has been an on-going
      challenge for the last decades primarily due to the issues of brain radiotherapy
      and radiation protection for astronauts during space travel. Although recent
      findings revealed a number of molecular mechanisms associated with radiation
      induced impairments in behaviour and cognition, some uncertainties exist in the
      initial neuronal cell injury leading to the further development of CNS
      malfunction. The present study is focused on the investigation of early
      biological damage induced by ionizing radiations in a sample neural network by
      means of modelling physico-chemical processes occurring in the medium after
      exposure. For this purpose, the stochastic simulation of incident particle tracks
      and water radiation chemistry was performed in realistic neuron phantoms
      constructed using experimental data on cell morphology. The applied simulation
      technique is based on using Monte-Carlo processes of the Geant4-DNA toolkit. The
      calculations were made for proton, 12C, and 56Fe particles of different energy
      within a relatively wide range of linear energy transfer values from a few to
      hundreds of keV/MUm. The results indicate that the neuron morphology is an
      important factor determining the accumulation of microscopic radiation dose and
      water radiolysis products in neurons. The estimation of the radiolytic yields in
      neuronal cells suggests that the observed enhancement in the levels of reactive
      oxygen species may potentially lead to oxidative damage to neuronal components
      disrupting the normal communication between cells of the neural network.

PMID- 27865671
TI  - Anomalous pulmonary venous connection: An underestimated entity.
AB  - Anomalous pulmonary venous connection is an uncommon congenital anomaly in which
      all (total form) or some (partial form) pulmonary veins drain into a systemic
      vein or into the right atrium rather than into the left atrium. The authors
      present one case of total anomalous pulmonary venous connection and two cases of
      partial anomalous pulmonary venous connection, one of supracardiac drainage into
      the brachiocephalic vein, and the other of infracardiac anomalous venous drainage
      (scimitar syndrome). Through the presentation of these cases, this article aims
      to review the main pulmonary venous developmental defects, highlighting the role
      of imaging techniques in the assessment of these anomalies.

PMID- 27865672
TI  - How should we interpret the athlete's electrocardiogram?

PMID- 27865673
TI  - A rare cause of acute coronary syndrome: Kounis syndrome.
AB  - Kounis syndrome is an acute coronary syndrome in the context of a
      hypersensitivity reaction. The main pathophysiological mechanism appears to be
      coronary vasospasm. We report the case of a patient with a history of allergy to
      quinolones, who was given ciprofloxacin before an elective surgical procedure and
      during drug administration developed symptoms and electrocardiographic changes
      suggestive of ST-segment elevation acute coronary syndrome. The drug was
      suspended and coronary angiography excluded epicardial coronary disease. Two
      hours after withdrawal of the drug the symptoms and ST elevation had resolved
      completely.

PMID- 27865674
TI  - Does anemia affect the predictive ability of bleeding risk scores in patients
      with acute coronary syndromes?
AB  - INTRODUCTION AND OBJECTIVE: Anemia is a common comorbidity in patients with acute
      coronary syndromes (ACS), and is associated with higher risk for both bleeding
      and ischemic complications. We aimed to assess the predictive ability of bleeding
      risk scores (Can Rapid risk stratification of Unstable angina patients Suppress
      ADverse outcomes with Early implementation of the ACC/AHA guidelines [CRUSADE],
      Mehran and Acute Coronary Treatment and Intervention Outcomes Network [ACTION])
      in ACS patients with anemia. METHODS: All consecutive ACS patients were
      prospectively included. The primary outcome was in-hospital major bleeding
      according to the CRUSADE, Mehran and ACTION definitions. Anemia was defined as
      hemoglobin <130 g/l in men and <120 g/l in women. The predictive ability of the
      bleeding risk scores was assessed by binary logistic regression, calculating
      receiver operating characteristic (ROC) curves and their corresponding area under
      the curve (AUC). RESULTS: We included 2255 patients, mean age 62.4 years. Anemia
      was present in 550 patients (24.4%). Patients with anemia had a significantly
      higher prevalence of comorbidities. The three bleeding risk scores adequately
      predicted major bleeding in the whole cohort. No significant differences were
      observed regarding the predictive ability of each of the scores in patients with
      and without anemia (CRUSADE: AUC 0.73 without anemia vs. 0.74 with anemia,
      p=0.913; ACTION: AUC 0.68 without anemia vs. 0.73 with anemia, p=0.353; Mehran:
      AUC 0.69 without anemia vs. 0.61 with anemia, p=0.210). Only the Mehran score
      showed significantly lower predictive ability in patients with hemoglobin <11
      g/dl (AUC 0.51, p=0.044). CONCLUSIONS: Anemia was a common comorbidity in
      patients with ACS from our series. Currently available bleeding risk scores
      showed an adequate predictive ability in patients with mild anemia.

PMID- 27865675
TI  - Unexpected diagnosis in a liver donor candidate.

PMID- 27865677
TI  - Segmental pulmonary stenosis: Importance of computed tomography angiography.

PMID- 27865676
TI  - Bailout intravenous esmolol for heart rate control in cardiac computed tomography
      angiography.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a heart rate (HR) reduction
      protocol using intravenous esmolol as bailout for failed oral metoprolol regimens
      in patients undergoing coronary computed tomography angiography (CCTA) with 64
      slice multidetector computed tomography (64-MDCT). METHODS: Patients who
      underwent cardiac 64-MDCT in a single institution between 2011 and 2014 were
      analyzed. Those with HR above 60 beats per minute (bpm) on presentation received
      oral metoprolol (50-200 mg) at least one hour before CCTA. Intravenous esmolol 1
      2 mg/kg was administered as a bolus whenever HR remained over 65 bpm just before
      imaging. The primary efficacy endpoint was HR <65 bpm during CCTA. The primary
      safety endpoint was symptomatic hypotension or bradycardia up to hospital
      discharge. RESULTS: During the study period CCTA was performed in 947 cases. In
      86% of these, oral metoprolol was the only medication required to successfully
      reduce HR <60 bpm. Esmolol was used in the remaining 130 patients (14%). For
      esmolol-treated patients mean baseline and acquisition HR were 74+/-14 bpm and
      63+/-9 bpm, respectively (p<0.001). The target HR of <65 bpm was achieved in 82
      of the 130 esmolol-treated patients (63%). Considering the whole population,
      esmolol use led to a significant increase in the primary efficacy endpoint from
      86% to 95% (p<0.001). Esmolol also resulted in a statistically, but not
      clinically, significant reduction in systolic blood pressure (144+/-22 to 115+/
      17 mmHg; p<0.001). The combined primary safety endpoint was only observed in two
      (1.5%) patients. CONCLUSION: Despite optimal use of oral beta-blockers, 14% of
      patients needed intravenous esmolol for HR control. The pre-medication
      combination of oral metoprolol and on-demand administration of intravenous
      esmolol was safe and effective and enabled 95% of patients to be imaged with HR
      below 65 bpm.

PMID- 27865678
TI  - Amorphous tumor of the mitral valve.

PMID- 27865679
TI  - Percutaneous closure of isolated ostium secundum-type atrial septal defect in a
      patient with Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a rare congenital anomaly
      characterized by complete or partial aplasia of the uterus and the upper part of
      the vagina. It is reported to be associated with cardiovascular disorders
      including atrial septal defect, anomalous pulmonary venous return, aortopulmonary
      window, pulmonary valve stenosis, mitral valve prolapse, tetralogy of Fallot,
      truncus arteriosus, and patent ductus arteriosus. Herein, for the first time in
      the medical literature, we present percutaneous closure of an isolated ostium
      secundum atrial septal defect in this syndrome.

PMID- 27865680
TI  - Mortality benefit of long-term angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers after successful percutaneous coronary intervention
      in non-ST elevation acute myocardial infarction.
AB  - INTRODUCTION AND OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEIs) and
      angiotensin receptor blockers (ARBs) have been shown to reduce mortality after
      myocardial infarction (MI). Current guidelines recommend their prescription in
      all patients after MI. Limited data are available on whether ACEIs/ARBs still
      improve prognosis in the contemporary era of non-ST elevation MI (NSTEMI)
      management. We aimed to evaluate the mortality benefit of ACEIs/ARBs in NSTEMI
      patients treated successfully with percutaneous coronary intervention (PCI).
      METHODS: We analyzed 2784 patients with NSTEMI treated successfully with in
      hospital PCI. Two groups were formed based on ACEI/ARB prescription at discharge.
      Two propensity score (PS) analyses were performed to control for differences in
      covariates: one with adjustment among the entire cohort, and the other with PS
      matching (n=1626). The outcome variable was all-cause mortality at four-year
      follow-up. RESULTS: There were 1902 (68.3%) patients prescribed ACEIs/ARBs at
      discharge. When adjusted by PS, ACEI/ARB use was associated with a hazard ratio
      (HR) for mortality of 0.75 (0.60-0.94; absolute risk reduction [ARR] 4.0%) in the
      whole cohort (p=0.01). After one-to-one PS matching (n=813 in each group), the
      mortality rate was significantly lower in patients prescribed ACEIs/ARBs, with HR
      of 0.77 (0.63-0.94; ARR 3.8%) (p=0.03). CONCLUSIONS: In this observational study
      of patients with NSTEMI, all of them treated successfully by PCI, the use of
      ACEIs/ARBs was significantly associated with a lower risk of four-year all-cause
      mortality.

PMID- 27865681
TI  - Cardiac rehabilitation in Portugal: The situation in 2013-2014.

PMID- 27865682
TI  - Cardiac rehabilitation in Portugal: Results from the 2013-14 national survey.
AB  - INTRODUCTION: In recent years, cardiac rehabilitation (CR) programs have evolved
      from being limited to exercise training to comprehensive secondary prevention
      programs. Given the solid scientific evidence supporting them, they are given a
      class I recommendation in the American and European guidelines for various
      cardiovascular diseases, but they continue to be underused in Portugal.
      OBJECTIVE: To analyze the situation of CR programs in Portugal in 2013-14 and to
      assess developments in recent years. METHODS: In November 2014, a questionnaire
      was sent to the centers offering CR programs that included the following items:
      name of the center; composition of the team; phases and components; number of
      participants and diagnoses; and funding bodies. The percentage of patients with
      myocardial infarction admitted to phase II CR programs in 2013 was calculated
      based on data from the Directorate-General of Health (DGS). RESULTS: Twenty-three
      centers offering CR programs were identified, 12 public and 11 private. The
      number of centers rose from 16 in 2007 to 23 in 2014. In 2013, 1927 patients
      participated in phase II programs, nearly three times the number rehabilitated in
      2007 (638 patients). Myocardial infarction was the referral diagnosis in 999
      patients, accounting for 51.8% of admissions. On the basis of DGS data, 8% of
      patients with myocardial infarction were admitted to phase II CRPs in 2013, as
      opposed to 3% in 2007. CONCLUSION: The number of patients admitted to CR
      programs, as well as the number of centers, increased considerably between 2007
      and 2014 in Portugal. Despite these favorable developments, further improvements
      are still needed.

PMID- 27865683
TI  - Health-related quality of life in children, adolescents and adults with
      hereditary and acquired bleeding disorders.
AB  - BACKGROUND: To better understand self-reported health-related quality-of-life
      (HrQoL) in children and adults with chronic hemostatic conditions compared with
      healthy controls. METHODS/PATIENTS/RESULTS: Group 1 consisted of 74
      children/adolescents aged 8-18years with hereditary bleeding disorders (H-BD), 12
      siblings and 34 peers. Group 2 consisted of 82 adult patients with
      hereditary/acquired bleeding disorders (H/A-BD), and group 3 of 198 patients with
      deep venous thrombosis (DVT) on anticoagulant therapy. Adult patients were
      compared to 1011 healthy blood donors. HrQoL was assessed with a 'revised KINDer
      Lebensqualitaetsfragebogen' (KINDL-R)-questionnaire adapted to adolescents and
      adults. No differences were found in multivariate analyses of self-reported HrQoL
      in children with H-BD. In contrast, apart from family and school-/work-related
      wellbeing in female patients with DVT the adult patients showed significantly
      lower HrQoL sub-dimensions compared to heathy control subjects. Furthermore,
      adults with H/A-BD disorders reported better friend-related HrQoL compared to
      patients with DVT, mainly due to a decreased HrQoL subscale in women on
      anticoagulation. CONCLUSION: In children with H-BD, HrQoL was comparable to
      siblings and peers. In adults with H/A-BD HrQoL was comparable to patients with
      DVT while healthy blood donors showed better HrQoL. The friend-related HrQoL
      subscale was significantly reduced in female compared to male patients.

PMID- 27865686
TI  - David Knopman: connecting the images in dementia research.

PMID- 27865684
TI  - Clinical and molecular characteristics of patients with Gaucher disease in
      Southern China.
AB  - Gaucher disease (GD) is a common lysosomal storage disorder caused by the
      deficiency of acid beta-glucosidase, due to mutations in the GBA gene. To explore
      the clinical and molecular characteristics of GD patients from Southern China,
      GBA gene were analyzed by nest PCR and direct Sanger-sequencing. Novel missense
      mutations were transiently transfected in COS-7 cells by plasmid system for
      functional verification. Among the 22 GD patients, 19 patients were classified as
      type 1 and three as type 2. Over 60% of the type 1 patient had the onset before
      two years of age and about 42% of them died before three years of age. Six type 1
      patients with L444P homozygous genotype, presented with early onset and severe
      hepatosplenomegaly. Four novel mutations Y22C, F109L, L149F and
      c.983_990delCCCACTGG were identified. The GBA activities in vitro of novel
      mutants Y22C, F109L and L149F were 20.2%, 6.9% and 6.5% of the wild-type,
      respectively. L444P mutation accounted for 47.7% of the mutant alleles. Our
      results revealed that type 1 GD tends to present with a severe phenotype among
      southern Chinese. L444P was the most prevalent mutation and L444P homozygous
      genotype was associated with severe type 1 GD. Three novel missense mutations
      identified were pathogenic.

PMID- 27865685
TI  - Mixed Epithelial and Stromal Tumor of the Kidney: Two Case Reports of a Rare
      Benign Kidney Tumor.

PMID- 27865687
TI  - Scoring system to predict hemorrhage in pelvic ring fracture.
AB  - BACKGROUND: Risk factors for hemorrhage in patients with pelvic ring fracture
      have been widely reported. Because there are many risk factors, it is thought
      that prediction accuracy of hemorrhage in cases of pelvic ring fracture could be
      improved by using a scoring system. HYPOTHESIS: We investigated the risk factors
      for massive hemorrhage (MH) and created a novel predictive score of MH in pelvic
      ring fractures. MATERIAL AND METHODS: We retrospectively reviewed patients with
      pelvic ring fractures (Abbreviated Injury Score>=3 and age>=16 years) from
      January 2007 to June 2015. We excluded the cases that might have hemorrhage from
      other sites sufficient to require a blood transfusion. Massive hemorrhage was
      defined as hemorrhage requiring transfusion of>=6 red cell concentrate units
      within 24h of admission. RESULTS: The MH group included 27 patients and the non
      MH group included 71 patients. Lactate level, AO/OTA classification and
      extravasation of computed tomography (CT) contrast fluid had a significantly
      higher risk as a result of multivariable analysis. The combined score using these
      risk factors according to their odds-adjusted ratios was created to predict for
      MH: lactate level>2.5-5.0 (mmol/L)=1 point,>5.0 (mmol/L)=2 points, partially
      stable (OA/OTA classification B1/B2/B3)=1 point, unstable (C1/C2/C3)=2 points,
      pelvic extravasation of contrast on CT=4 points. The AUC of the calculated score
      was 0.93 (95% CI: 0.89-0.98). CONCLUSION: The combined score using these risk
      factors according to their odds-adjusted ratios was created to predict MH and was
      an effective prediction score. LEVEL OF EVIDENCE: IV, retrospective study.

PMID- 27865688
TI  - [Cataract surgery with topical anesthesia in adults under 30 years of age:
      Preliminary study].

PMID- 27865690
TI  - [Waardenburg syndrome].

PMID- 27865689
TI  - Retinal oximetry during treatment of retinal vein occlusion by ranibizumab in
      patients with high blood pressure and dyslipidemia.
AB  - INTRODUCTION: In the present study, we examined retinal vascular oxygen
      saturation in patients with retinal vein occlusion (RVO), high blood pressure
      (HBP) and dyslipidemia, before and during intravitreal vascular endothelial
      growth factor (VEGF) injection (ranibizumab). METHODS: We retrospectively
      reviewed the medical records of six patients with visual acuity (VA) reduced by
      macular edema (ME) secondary to RVO with HBP and dyslipidemia, who underwent
      intravitreal anti-VEGF injection between October 2014 and February 2015 in the
      department of ophthalmology of Francois-Quesnay Hospital at Mantes-la-Jolie
      (France). The main inclusion criterion was the presence of RVO with ME and
      decreased VA. The primary endpoint was improvement of retinal venous oxygen
      saturation in patients with RVO before and 3 months after intravitreal
      ranibizumab injection. Secondary outcomes were improvement of retinal arterial
      oxygen saturation, improvement of best-corrected visual acuity (BCVA) on the
      Early Treatment Diabetic Retinopathy Study (ETDRS) scale, regression of ME
      measured by the central macular thickness (CMT) in nm and studying the
      correlation between blood pressure (BP) and retinal venous oxygen saturation
      before and after ranibizumab. RESULTS: Six eyes of six patients were included.
      Before treatment, the mean (standard deviation [SD]) of the retinal venous
      saturation (%) was 38.1+/-14.2. Three months after the injections, the mean (SD)
      of the retinal venous saturation (%) increased statistically significantly 49.2+/
      11 (P=0.03). CONCLUSION: In this study, retinal venous oxygen saturation in
      patients with RVO, HBP and dyslipidemia was partially normalized during
      intravitreal ranibizumab treatment.

PMID- 27865691
TI  - [Evaluation of vision quality after laser vision correction in healthcare
      professionals].
AB  - PURPOSE: Healthcare professionals require good quality of vision. The main
      objective of this study is to evaluate the satisfaction and vision quality after
      laser vision correction in healthcare professionals. METHODS: This is a
      monocentric retrospective study. An online 25-question survey was sent to
      ametropic physicians, surgeons and nurses who underwent corneal refractive
      surgery with laser-assisted in situ keratomileusis (LASIK) or photorefractive
      keratectomy (PRK) between July 2012 and February 2016. Questionnaire responses
      were recorded anonymously by the internet survey site. These patients' pre- and
      postoperative data were analyzed. RESULTS: In total, 2491 laser vision
      corrections were performed during this time frame. One hundred and fifty-eight
      patients were healthcare providers; 131 received the survey, and 111 responded.
      Ninety-nine were surgeons, 60 were medical physicians, and 32 were nurses. Ninety
      one percent reported that they were satisfied with their postoperative vision
      quality, 63.9% even reported an improvement in their quality of vision compared
      with their corrected preoperative vision, 92.8% reported that they would have the
      procedure again, and 94.6% would recommend the procedure to a family member or a
      patient. Visual outcomes showed high levels of efficacy and predictability.
      CONCLUSION: While healthcare professionals require good quality of vision, those
      who had undergone laser vision correction reported the same satisfaction as the
      general population and would recommend the procedure to their family, friends and
      patients.

PMID- 27865692
TI  - Elimination of blinding trachoma in China.
AB  - OBJECTIVE: To present the change in the prevalence of blindness caused by
      trachoma between 1987 and 2006 by secondary data analysis based on two China
      National Sample Surveys on Disability (CNSSD). METHODS: Secondary data analysis
      was performed on two China National Sample Surveys on Disability (CNSSD), which
      were national representative household surveys conducted in 1987 and 2006. The
      prevalence of blindness caused by trachoma was estimated by 10-year age group. In
      addition, the proportion of various causes of blindness was evaluated. The
      geographical distribution of blindness caused by trachoma both in 1987 and 2006
      was analyzed in order to visualize the hot spots of blinding trachoma in China.
      RESULTS: The prevalence of blindness caused by trachoma in China decreased from
      51.5/100,000 in 1987 to 17.6/100,000 in 2006. In addition, the proportion of
      blindness attributed to trachoma also decreased from 10.1% (1987) to 0.9% (2006).
      Moreover, the prevalence of blindness caused by trachoma was over 200/100,000 in
      2.2% of sampled counties in 2006 as compared to 8.6% in 1987. The hot spots of
      blinding trachoma were shown to be limited to underdeveloped mountain areas in
      Hubei and Guizhou provinces. CONCLUSION: Although blinding trachoma is no longer
      the leading cause of blindness in China since the 2000's, the prevalence of
      trachoma should still be monitored in some underdeveloped mountain areas.
      Therefore, health organization must continue to fight against blinding trachoma
      in underdeveloped areas.

PMID- 27865694
TI  - Ocular amyloidosis: A direct view of the amyloid plaques.

PMID- 27865693
TI  - ["Point by point" approach to structure-function correlation of glaucoma on the
      ganglion cell complex in the posterior pole].
AB  - PURPOSE: To try to establish a "point by point" relationship between the local
      thickness of the retinal ganglion cell complex and its sensitivity. MATERIALS AND
      METHODS: In total, 104 glaucomatous eyes of 89 patients with a confirmed 24-2
      visual field, were measured by superimposing the visual field, using imaging
      software, with the Wide 40 degrees  by 30 degrees  measurements of retinal
      ganglion cell complex obtained from the Topcon(c) 3D 2000 OCT, after upward
      adjustment, inversion and scaling. Visual fields were classified into two groups
      according to the extent of the disease: 58 mild to moderate (MD up to -12dB), and
      46 severe (MD beyond -12dB). The 6mm by 6mm central region, equipped with a
      normative database, was studied, corresponding to 16 points in the visual field.
      These points were individually matched one by one to the local ganglion cell
      complex, which was classified into 2 groups depending on whether it was greater
      or less than 70 microns. The normative database confirmed the pathological nature
      of the thin areas, with a significance of 95 to 99%. Displacement of central
      retinal ganglion cells was compensated for. Of 1664 points (16 central points for
      104 eyes), 283 points were found to be "borderline" and excluded. Of the 1381
      analyzed points, 727 points were classified as "over 70 microns" and 654 points
      "under 70 microns". RESULTS: (1) For all stages combined, 85.8% of the 727 points
      which were greater than 70 microns had a deviation between -3 and +3dB: areas
      above 70 microns had no observable loss of light sensitivity. (2) In total, 92.5%
      of the 428 points having a gap ranging from -6 to -35dB were located on ganglion
      cell complex areas below 70 microns: functional visual loss was identified in
      thin areas, which were less than 70 microns. (3) Areas which were less than 70
      microns, that is 654 points, had quite variable sensitivity and can be divided
      into three groups: the first with preserved sensitivity, another with obliterated
      sensitivity, and an intermediate group connecting the two previous ones.
      DISCUSSION: In pathologically thin areas, the distribution of these three
      functional groups seems to correspond to the progression of glaucomatous visual
      degradation, including a period of resistance, a period of rapid decline, finally
      leading to complete functional loss. CONCLUSION: In the studied area, the
      analysis of retinal ganglion cell complex is relevant to identify areas which are
      still functional when they exceed 70 microns. Scotomas correspond to the thin
      areas less than 70 microns. The functionality of areas which are pathologically
      thinned by glaucomatous degeneration is not correlated to their thickness. In the
      future, the correlation between structure and function, currently "regional" may
      be realized "point by point" once automation of the visual field superimposition
      is made available for the ganglion cell complex.

PMID- 27865695
TI  - Fusiform Left Carotid-Ophthalmic Artery Aneurysm Presenting with Central Retinal
      Artery Occlusion.
AB  - Central retinal artery occlusion (CRAO) is a devastating ocular emergency
      characterized by acute painless visual loss in the ipsilateral eye. We describe
      the case of acute non-arteritic CRAO associated fusiform internal carotid
      ophthalmic artery aneurysm with intraluminal thrombus. Despite the rarity of this
      condition, we suggest that carotid-ophthalmic artery aneurysm should be included
      in the differential diagnosis of CRAO.

PMID- 27865696
TI  - Strength Training for Skeletal Muscle Endurance after Stroke.
AB  - BACKGROUND AND PURPOSE: Initial studies support the use of strength training (ST)
      as a safe and effective intervention after stroke. Our previous work shows that
      relatively aggressive, higher intensity ST translates into large effect sizes for
      paretic and non-paretic leg muscle volume, myostatin expression, and maximum
      strength post-stroke. An unanswered question pertains to how our unique ST model
      for stroke impacts skeletal muscle endurance (SME). Thus, we now report on ST
      induced adaptation in the ability to sustain isotonic muscle contraction.
      METHODS: Following screening and baseline testing, hemiparetic stroke
      participants were randomized to either ST or an attention-matched stretch control
      group (SC). Those in the ST group trained each leg individually to muscle failure
      (20 repetition sets, 3* per week for 3 months) on each of three pneumatic
      resistance machines (leg press, leg extension, and leg curl). Our primary outcome
      measure was SME, quantified as the number of submaximal weight leg press
      repetitions possible at a specified cadence. The secondary measures included one
      repetition maximum strength, 6-minute walk distance (6MWD), 10-meter walk speeds,
      and peak aerobic capacity (VO2 peak). RESULTS: ST participants (N = 14) had
      significantly greater SME gains compared with SC participants (N = 16) in both
      the paretic (178% versus 12%, P < .01) and non-paretic legs (161% versus 12%, P <
      .01). These gains were accompanied by group differences for 6MWD (P < .05) and
      VO2 peak (P < .05). CONCLUSION: Our ST regimen had a large impact on the capacity
      to sustain submaximal muscle contraction, a metric that may carry more practical
      significance for stroke than the often reported measures of maximum strength.

PMID- 27865697
TI  - Sulfonylurea Pretreatment and In-Hospital Use Does Not Impact Acute Ischemic
      Strokes (AIS) Outcomes Following Intravenous Thrombolysis.
AB  - BACKGROUND AND PURPOSE: Preliminary studies have indicated that sulfonylurea
      drugs (SUD) may confer protection against cerebral swelling and hemorrhagic
      transformation in severe acute ischemic stroke (AIS). We sought to determine
      whether pretreatment and in-hospital use of SUD may be associated with better
      outcomes in diabetic AIS patients treated with intravenous thrombolysis (IVT).
      SUBJECTS AND METHODS: We analyzed consecutive diabetic AIS patients treated with
      IVT during a 3-year period. Pretreatment with SUD, admission NIHSS (National
      Institutes of Health Stroke Scale) score, NIHSS at 48 hours, and modified Rankin
      Scale (mRS) at discharge were documented. Patients who discontinued SUD during
      hospitalization were excluded. Symptomatic intracranial hemorrhage (sICH) was
      defined as imaging evidence of ICH with NIHSS score increase of greater than or
      equal to 4 points within 72 hours. Early neurological improvement was defined as
      an NIHSS score decrease of greater than or equal to 4 points or NIHSS score of 0
      at 48 hours. Cerebral edema was documented by neuroradiology reports. Favorable
      functional outcome (FFO) was defined as discharge mRS of 0-1. RESULTS: A total of
      148 diabetic AIS patients were evaluated (mean age 64 +/- 11 years, 49% men,
      median admission NIHSS score: 8 points). We identified 42 (28%) cases pretreated
      with SUD. The prevalence of complications and favorable outcomes did not differ
      (P > .1) between patients pretreated and nonpretreated with SUD: sICH (2% versus
      5%), cerebral edema (5% versus 4%), early neurological improvement (42% versus
      43%), in-hospital mortality (12% versus 5%), and FFO (22% versus 32%).
      CONCLUSIONS: Pretreatment and in-hospital use of SUD appears not to be associated
      with early favorable outcomes and lower likelihood of potential complications in
      diabetic AIS patients treated with IVT.

PMID- 27865698
TI  - Immunohistochemical Analysis of Debris Captured by Filter-Type Distal Embolic
      Protection Devices for Carotid Artery Stenting.
AB  - BACKGROUND: Little is known about the micro-debris captured in filter-type distal
      embolic protection devices (EPD) used for carotid stenting (CAS). This study
      aimed to determine the histological and immunohistochemical characteristics of
      such debris by using a new liquid-based cytology (LBC) technique. METHODS:
      Fifteen patients who underwent CAS using a filter-type distal EPD (FilterWire EZ;
      Boston Scientific, Marlborough, MA, USA) were included in the study. After gross
      inspection of each recovered filter device, micro-debris were collected using a
      new LBC technique (SurePath; TriPath Imaging, Inc., Burlington, NC). Histological
      and immunohistochemical analysis of the recovered debris was performed. The pre-
      and postoperative brain magnetic resonance imaging and neurological status of
      each patient were also reviewed. RESULTS: No patient developed ipsilateral
      symptomatic stroke due to a thromboembolic event. All 15 patients (100%) had
      microscopically identifiable debris in the filters, whereas gross inspection
      detected visible debris only in 5 patients (33.3%). Histological analysis
      revealed various types of structural components in an advanced atheromatous
      plaque, including fragments of fibrous cap, calcified plaque, smooth muscle
      cells, and necrotic tissue fragment infiltrated with monocytes and macrophages.
      CONCLUSIONS: Filter-type EPDs may contribute to reducing the risk of CAS-related
      embolic events by capturing micro-debris even when gross inspection of the
      recovered filter shows no visible debris in the device.

PMID- 27865699
TI  - TNF-alpha inhibits the growth of Legionella pneumophila in airway epithelial
      cells by inducing apoptosis.
AB  - BACKGROUND: TNF-alpha plays an important role in the pathogenesis of Legionella
      pneumophila (Lp)-induced pneumonia. Patients undergoing anti-TNF-alpha therapy
      are at an increased risk of Lp infection. Lp infects both phagocytic and non
      phagocytic cells such as airway epithelial cells; however, the role of TNF-alpha
      in airway epithelial cells is unknown. METHODS: Human airway epithelial cell line
      NCI-H292 was infected with Lp NUL1 strain. After infection, both intracellular
      growth of Lp and cell death were evaluated after treating the cells with or
      without TNF-alpha. Apoptosis was examined by performing activated caspase-3/7
      staining and by using a pan-caspase inhibitor. RESULTS: Lp infected and
      replicated in NCI-H292 cells in a time-dependent manner, and TNF-alpha treatment
      of Lp-infected NCI-H292 cells inhibited Lp replication. Inhibitory effects of TNF
      alpha on Lp replication were suppressed after treatment with a TNF-alpha
      neutralizing antibody. Lp infection increased extracellular lactate dehydrogenase
      levels and decreased the number of living cells. Increased number of Lp-infected
      NCI-H292 cells showed caspase-3/7 activation, indicating they underwent
      apoptosis. TNF-alpha treatment inhibited Lp replication by increasing the
      apoptosis of NCI-H292 cells. CONCLUSIONS: Thus, our results suggested that airway
      epithelial cells were involved in the pathogenesis of Lp infection and that TNF
      alpha played a protective role by inhibiting the intracellular replication of Lp
      and by increasing the apoptosis of Lp-infected airway epithelial cells. However,
      Lp infection should be investigated further in patients undergoing anti-TNF-alpha
      therapy who develop pneumonia.

PMID- 27865700
TI  - Adhesion ability of angiotensin II with model membranes.
AB  - The octa-peptide angiotensin II (Ang II, (H2NAspArgValTyrIleHisProPheCOOH)) is
      one of the key player on blood pressure regulation in mammals. Predominantly
      binding to the Angiotensin type 1 and 2 receptors, the hormone is one of several
      peptide ligands binding to G protein coupled receptors (GPCR). The active hormone
      derives from a high molecular weight precursor sequentially cleaved by the
      proteases renin and the angiotensin converting enzyme (ACE). The chemical nature
      of the amino acid sequence has an impact on the behavior in the proximity of
      membranes, demonstrated using different membrane model systems and biophysical
      methods. Applying electrochemical impedance spectroscopy and small angle X-ray
      scattering a detailed view on the adhesion of the peptide with model membrane
      surfaces was performed. The role of specific amino acids involved in the
      interaction with the phospholipid head group were investigated and, studying a
      truncated version of Ang II, Ang (1-7), the key role of the C-terminal
      phenylalanine was proven. Truncation of the C-terminal amino acid abolishes the
      binding of the peptide to the membrane surface. A shift in pH, altering the
      protonation state of the central histidine residue impairs the adhesion of Ang
      II.

PMID- 27865701
TI  - Polymorphisms and haplotypes of the CYP2B6 detoxification gene in the
      predisposition of Acute Myeloid Leukemia (AML) and induction of its cytogenetic
      abnormalities.
AB  - CYP2B6 is a polymorphic detoxification gene which plays a vital role in the
      degradation of genotoxic compounds. In this study we hypothesized that inadequate
      detoxification due to CYP2B6 polymorphisms may contribute to AML. To evaluate the
      potential impact of CYP2B6 polymorphisms on AML development and induction of its
      specific chromosomal abnormalities we studied C777A and A785G polymorphisms for
      the first time in AML. Furthermore, we investigated the co-existence of the above
      polymorphisms with G516T polymorphism to determine the CYP2B6 high-risk
      haplotypes in AML susceptibility. Our study included 619 AML patients and 430
      healthy donors. Concerning C777A CYP2B6 polymorphism, no significant difference
      was found between patients and controls. However, A785G CYP2B6 polymorphism
      showed a statistically higher frequency of the variant genotypes in patients
      (48.2%), mainly in secondary AML patients (49.1%) than in controls (26.1%).
      Moreover, an increased frequency of the variant genotypes was found in those with
      abnormal karyotypes, especially with -7/del(7q), -5/del(5q), +8, inv(16) and
      t(8;21). The combination of the three CYP2B6 polymorphisms (G516T, C777A & A785G)
      revealed seven haplotypes. Four out of six haplotypes with at least one mutant
      allele were significantly associated with an increased risk for AML.
      Interestingly, T516A777G785 haplotype, where the three mutant alleles co-existed,
      had ~3-fold increased risk to be found in patients than controls. The association
      between haplotypes and cytogenetic aberrations revealed a positive correlation
      between specific CYP2B6 haplotypes and AML cytogenetic abnormalities. Our data
      suggest that A785G CYP2B6 gene polymorphism and specific CYP2B6 haplotypes may
      contribute to AML and its specific chromosomal aberrations.

PMID- 27865702
TI  - Biosynthetic approaches to creating bioactive fungal metabolites: Pathway
      engineering and activation of secondary metabolism.
AB  - The diversity of natural products is greater than that of combinatorial chemistry
      compounds and is similar to that of drugs. Compounds rich in sp3 carbons, such as
      natural products, typically exhibit high structural complexity and high
      specificity to molecular targets. Microorganisms can synthesize such sp3 carbon
      rich compounds and can be used as excellent factories for making bioactive
      compounds. Here, we mainly focus on pathway engineering of two sp3 carbon-rich
      bioactive indole alkaloids, fumitremorgin C and terpendole E. We also demonstrate
      the importance of activation of secondary metabolism by focusing on tenuazonic
      acid, a bioactive tetramic acid compound, as an example.

PMID- 27865703
TI  - Discovery of 2-((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5
      (trifluoromethyl)phenyl)-1-methyl-7,8-dihydro-1H-[1,4]dioxino[2',3':3,4]benzo[1,2
      d]imidazole-5-carboxamide as potent, selective and efficacious microsomal
      prostaglandin E2 synthase-1 (mPGES-1) inhibitor.
AB  - The discovery and SAR of potent, selective dioxane-fused tricyclic
      benz[d]imidazole derivatives as mPGES-1 inhibitor are herein described. Various
      amide modifications in this series afforded many potent mPGES-1 inhibitors, of
      which 17d proved to be suitable for further profiling in vivo. Compound 17d {2
      ((2-chloro-6-fluorophenyl)amino)-N-(3-fluoro-5-(trifluoromethyl)phenyl)-1-methyl
      7,8-dihydro-1H-[1,4]dioxino[2',3':3,4]benzo[1,2-d]imidazole-5-carboxamide}
      exhibited excellent mPGES-1 enzyme (IC50: 8nM), cell (A549 IC50: 16.24nM) and
      human whole blood potency (IC50: 249.9nM). In rodent species, 17d strongly
      inhibited guinea pig mPGES-1 (IC50: 10.79nM), but not the rat and mouse enzyme.
      Furthermore 17d displayed excellent in vitro selectivity over mPGES-2, cPGES, COX
      enzymes (COX-1, 2), selectivity against other prostanoid synthases, favorable
      hERG and CEREP panel profile. Likewise, our lead 17d demonstrated good oral
      pharmacokinetic profiles and good CNS B/P ratio in rat and guinea pig. Lead 17d
      also unveiled good efficacy in LPS-induced thermal hyperalgesia pain model with
      ED50 of 36.7mg/kg, respectively.

PMID- 27865704
TI  - Radical scavenging and antibacterial activity of caffemides against gram
      positive, gram negative and clinical drug resistance bacteria.
AB  - A new series of caffemide were synthesized and their antioxidant and
      antibacterial activities were explored. Antioxidant and antibacterial activities
      were measured of different structures of caffemide containing different
      functional groups. Anti-oxidative caffemides 1b and 1g showed significantly
      higher activity against different bacteria with MIC values less than 50MUg/ml.
      These anti-oxidative and antibacterial properties of caffemides might be helpful
      for the treatment of secondary infections and discovery of new antibiotics.

PMID- 27865705
TI  - Dimeric sesquiterpene and thiophenes from the roots of Echinops latifolius.
AB  - Phytochemical investigation of the roots of Echinops latifolius led to the
      isolation of a new carbon skeleton dimeric sesquiterpene (1) and a new thiophene
      (2), along with six known compounds (3-8). Their structures and relative
      stereochemistry were elucidated by spectroscopic and spectrometric methods (1H
      and 13C NMR, COSY, HSQC, HMBC, ROESY, and MS). All isolates were evaluated for
      their inhibition of LPS-induced NO production in RAW 264.7 cells. Compounds 4 and
      5 exhibited the most potent inhibitory effects on NO production.

PMID- 27865706
TI  - Age-related length variability of polymorphic CAG repeats.
AB  - Somatic instability of CAG repeats has been associated with the clinical
      progression of CAG repeat diseases. Aging and DNA repair processes influence the
      somatic stability of CAG repeat in disease and in mouse models. However, most of
      the studies have focused on genetically engineered transgenic repeats and little
      is known about the stability of naturally polymorphic CAG repeats. To study
      whether age and/or DNA repair activity have an effect on the somatic stability of
      CAG repeats, we analyzed variations of the length of naturally polymorphic CAG
      repeats in the striatum of young and aged WT and ogg1 KO mice. Some multiple and
      long polymorphic CAG repeats were observed to have variable length in the
      striatum of aged mice. Interestingly, a low level of repeat variability was
      detected in the CAG repeat located in tbp, the only mouse polymorphic CAG repeat
      that is associated with a trinucleotide disease in humans, in the striatum of
      aged mice and not in young mice. We propose that age may have an effect on the
      somatic stability of polymorphic CAG repeats and that such an effect depends on
      intrinsic CAG repeat characteristics.

PMID- 27865707
TI  - A comprehensive database of published tDCS clinical trials (2005-2016).
AB  - Transcranial direct current stimulation (tDCS) is a technique of noninvasive
      cortical stimulation allowing significant modification of brain functions.
      Clinical application of this technique was reported for the first time in March
      2005. This paper presents a detailed list of the 340 articles (excluding single
      case reports) which have assessed the clinical effect of tDCS in patients, at
      least when delivered to cortical targets. The reviewed conditions were: pain
      syndromes, Parkinson's disease, dystonia, cerebral palsy, post-stroke limb motor
      impairment, post-stroke neglect, post-stroke dysphagia, post-stroke aphasia,
      primary progressive aphasia, multiple sclerosis, epilepsy, consciousness
      disorders, Alzheimer's disease and other types of dementia, tinnitus, depression,
      auditory hallucinations and negative symptoms of schizophrenia, addiction and
      craving, autism, and attention disorders. The following data were collected: (i)
      clinical condition; (ii) study design; (iii) sample size; (iv) anode and cathode
      locations; (v) stimulation intensity and electrode area; (vi) number and duration
      of sessions; (vii) clinical outcome measures and results. This article does not
      include any meta-analysis and aims simply at providing a comprehensive overview
      of the raw data reported in this field to date, as an aid to researchers.

PMID- 27865708
TI  - Effects of exposure to 2100MHz GSM-like radiofrequency electromagnetic field on
      auditory system of rats.
AB  - INTRODUCTION: The use of mobile phones has become widespread in recent years.
      Although beneficial from the communication viewpoint, the electromagnetic fields
      generated by mobile phones may cause unwanted biological changes in the human
      body. OBJECTIVE: In this study, we aimed to evaluate the effects of 2100MHz
      Global System for Mobile communication (GSM-like) electromagnetic field,
      generated by an electromagnetic fields generator, on the auditory system of rats
      by using electrophysiological, histopathologic and immunohistochemical methods.
      METHODS: Fourteen adult Wistar albino rats were included in the study. The rats
      were divided randomly into two groups of seven rats each. The study group was
      exposed continuously for 30days to a 2100MHz electromagnetic fields with a signal
      level (power) of 5.4dBm (3.47mW) to simulate the talk mode on a mobile phone. The
      control group was not exposed to the aforementioned electromagnetic fields. After
      30days, the Auditory Brainstem Responses of both groups were recorded and the
      rats were sacrificed. The cochlear nuclei were evaluated by histopathologic and
      immunohistochemical methods. RESULTS: The Auditory Brainstem Responses records of
      the two groups did not differ significantly. The histopathologic analysis showed
      increased degeneration signs in the study group (p=0.007). In addition,
      immunohistochemical analysis revealed increased apoptotic index in the study
      group compared to that in the control group (p=0.002). CONCLUSION: The results
      support that long-term exposure to a GSM-like 2100MHz electromagnetic fields
      causes an increase in neuronal degeneration and apoptosis in the auditory system.

PMID- 27865709
TI  - Defective splicing of the background K+ channel K2P5.1 by the pre-mRNA splicing
      inhibitor, pladienolide B in lectin-activated mouse splenic CD4+ T cells.
AB  - The two-pore domain K+ channel K2P5.1 has been implicated in the pathogenesis of
      autoimmune diseases. We investigated the changes in K2P5.1 activity caused by a
      defect in normal pre-mRNA splicing in concanavalin A-activated mouse splenic CD4+
      T cells. The pre-mRNA splicing inhibitor, pladienolide B (1 MUM) markedly
      decreased full-length K2P5.1 transcription in activated CD4+ T cells, resulting
      in the disappearance of K2P5.1 activity and an imbalance in Th17 and Treg
      cytokines. These results suggest that the defect in K2P5.1 splicing by the pre
      mRNA splicing inhibitor regulates pro- and/or anti-inflammatory cytokine
      production in K2P5.1-associated autoimmune diseases.

PMID- 27865710
TI  - New human biomonitoring methods for chemicals of concern-the German approach to
      enhance relevance.
AB  - In Germany strong efforts have been made within the last years to develop new
      methods for human biomonitoring (HBM). The German Federal Ministry for the
      Environment, Nature Conservation, Building and Nuclear Safety (BMUB) and the
      German Chemical Industry Association e. V. (VCI) cooperate since 2010 to increase
      the knowledge on the internal exposure of the general population to chemicals.
      The projects aim is to promote human biomonitoring by developing new analytical
      methods Key partner of the cooperation is the German Environment Agency (UBA)
      which has been entrusted with the scientific coordination. Another key partner is
      the "HBM Expert Panel" which each year puts together a list of chemicals of
      interest to the project from which the Steering Committee of the project choses
      up to five substances for which method development will be started. Emphasis is
      placed on substances with either a potential health relevance or on substances to
      which the general population is potentially exposed to a considerable extent. The
      HBM Expert Panel also advises on method development. Once a method is developed,
      it is usually first applied to about 40 non-occupationally exposed individuals. A
      next step is applying the methods to different samples. Either, if the time trend
      is of major interest, to samples from the German Environmental Specimen Bank, or,
      in case exposure sources and distribution of exposure levels in the general
      population are the focus, the new methods are applied to samples from children
      and adolescents from the population representative 5th German Environmental
      Survey (GerES V). Results are expected in late 2018. This article describes the
      challenges faced during method development and solutions found. An overview
      presents the 34 selected substances, the 14 methods developed and the 7 HBM-I
      values derived in the period from 2010 to mid 2016.

PMID- 27865711
TI  - Use of an ePTFE-covered nitinol self-expanding stent graft for the treatment off
      pre-closure device failure during transcatheter aortic valve replacement.
AB  - OBJECTIVES: Our aim was to describe our experience with the use of an ePTFE
      covered nitinol self-expanding stent graft (GORE(r) VIABAHN(r) Endoprosthesis,
      Gore Medical, USA) placed in the common femoral artery for the treatment of
      suture-mediated pre-closure device failure following transcatheter aortic valve
      replacement (TAVR). BACKGROUND: Access site-related vascular complications (VC)
      following sheath removal related to pre-closure device failure during TAVR are
      common and treatment options may vary. METHODS: We performed an observational
      study on a series of consecutive patients who underwent TAVR between 2013 and
      2015. RESULTS: Included were 25 patients at a mean (+/-SD) age of 82+/-9. Failure
      of the closure device resulted in overt bleeding in 19 patients, dissection or no
      flow in 5 patients, and angiographic pseudoaneurysm in 1. Overall 29 stents were
      deployed with diameters ranging from 8 to 11mm and a length of 50mm (26, 90%).
      All stent-graft deployments achieved complete hemostasis of the arteriotomy site
      and resulted in normal flow to the distal vessels. None of the patients required
      open surgical repair. The mean hemoglobin drop was 2.6+/-1.3g/dl. Blood
      transfusions were used in 15 (60%) patients. Acute kidney injury occurred in 4
      (16%) patients, none of whom was treated with dialysis. Length of hospital stay
      was 9+/-5days. All patients survived during a 30-day follow-up period, and none
      had VC related to the stented site. CONCLUSIONS: The use of an ePTFE-covered
      Nitinol self-expanding stent graft is a feasible, safe, and effective treatment
      modality for access site-related VC following TAVR. SUMMARY: The use of an ePTFE
      covered nitinol self-expanding stent graft placed in the common femoral artery
      for the treatment of suture-mediated pre-closure device failure following
      transcatheter aortic valve replacement (TAVR) is described in 25 patients. Its
      use was found to be feasible, safe, and an effective treatment modality for
      access site-related vascular complications following TAVR.

PMID- 27865712
TI  - Role for human arylamine N-acetyltransferase 1 in the methionine salvage pathway.
AB  - The Phase II drug metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) has
      been implicated in the growth and survival of cancer cells, although the
      mechanisms that underlies these effects are unknown. Here, a focused metabolomics
      approach was used to identify changes in folate catabolism as well as the S
      adenosylmethionine (SAM) cycle following NAT1 knockdown with shRNA. Although
      acetylation of the folate catabolite p-aminobenzoylglutamate (pABG) was
      significantly decreased, there were no changes in intracellular pABG or the
      various components of the SAM cycle. By contrast, the flux of homocysteine in the
      medium was different following NAT1 knockdown after the methionine content was
      exhausted suggesting a need for this metabolite in methionine synthesis. Analysis
      of the growth of various cancer cells in methylthioadenosine-supplemented medium
      showed that NAT1 knockdown inhibited the methionine salvage pathway in HT-29
      cells but not in HeLa or MDA-MB-436 cells. The cause of this was a low level of
      expression of the isomerase MRI-1 in the HT-29 cells. Knocking down both NAT1 and
      MRI-1 in HeLa cells with siRNA further demonstrated a redundancy between these 2
      enzymes, although direct isomerase activity by NAT1 could not be demonstrated.
      The present study has identified a novel endogenous role for human NAT1 that
      might explain some of its effects in cancer cell growth and survival.

PMID- 27865714
TI  - Short-term prophylactic use of C1-inhibitor concentrate in hereditary angioedema:
      Findings from an international patient registry.

PMID- 27865715
TI  - Time-dependent severity change during treatment of pediatric patients
      hospitalized for acute asthma exacerbations.

PMID- 27865716
TI  - Common variable immune deficiency associated with pemphigoid.

PMID- 27865713
TI  - Platensimycin and platencin: Inspirations for chemistry, biology, enzymology, and
      medicine.
AB  - Natural products have served as the main source of drugs and drug leads, and
      natural products produced by microorganisms are one of the most prevalent sources
      of clinical antibiotics. Their unparalleled structural and chemical diversities
      provide a basis to investigate fundamental biological processes while providing
      access to a tremendous amount of chemical space. There is a pressing need for
      novel antibiotics with new mode of actions to combat the growing challenge of
      multidrug resistant pathogens. This review begins with the pioneering discovery
      and biological activities of platensimycin (PTM) and platencin (PTN), two
      antibacterial natural products isolated from Streptomyces platensis. The
      elucidation of their unique biochemical mode of action, structure-activity
      relationships, and pharmacokinetics is presented to highlight key aspects of
      their biological activities. It then presents an overview of how microbial
      genomics has impacted the field of PTM and PTN and revealed paradigm-shifting
      discoveries in terpenoid biosynthesis, fatty acid metabolism, and antibiotic and
      antidiabetic therapies. It concludes with a discussion covering the future
      perspectives of PTM and PTN in regard to natural products discovery, bacterial
      diterpenoid biosynthesis, and the pharmaceutical promise of PTM and PTN as
      antibiotics and for the treatment of metabolic disorders. PTM and PTN have
      inspired new discoveries in chemistry, biology, enzymology, and medicine and will
      undoubtedly continue to do so.

PMID- 27865717
TI  - Eosinophilic esophagitis as possible complication of aspirin treatment in patient
      with aspirin-exacerbated respiratory disease.

PMID- 27865718
TI  - Are Echocardiography and CMR Really Discordant in Mitral Regurgitation?

PMID- 27865720
TI  - The Female Side of the Heart: Sex Differences in Athlete's Heart.

PMID- 27865719
TI  - Pre-Load-Induced Changes in Forward LV Stroke and Functional Mitral
      Regurgitation: Echocardiographic Detection of the Descending Limb of Starling's
      Curve.
AB  - OBJECTIVES: The purpose of this study was to clarify the prognostic significance
      of diagnosing whether the failing heart is functioning on the descending limb of
      the Starling curve by using echocardiography with passive leg lifting (PLL).
      BACKGROUND: Patients with advanced heart failure can shift to the descending limb
      of the Starling curve, in which pre-load does not lead to an expected increase in
      forward left ventricular stroke volume (LVSV). METHODS: Thirty-five consecutive
      patients with left ventricular (LV) ejection fraction of <40% underwent
      echocardiography at rest during baseline and during PLL to increase pre-load.
      RESULTS: Despite PLL, a paradoxical decrease in forward LVSV was observed in 15
      (43%) patients. Changes in forward LVSV inversely correlated with those in
      functional mitral regurgitation (r = -0.56). The primary endpoint of cardiac
      death or hospitalization due to worsening heart failure occurred in 15 (43%)
      patients during follow-up (2.8 +/- 2.2 years). There were a number of significant
      predictors of the primary endpoint in the univariate Cox analysis: baseline E/A
      ratio (p = 0.0002), paradoxical decrease in LVSV despite PLL (hazard ratio: 4.44;
      95% confidence interval: 1.41 to 14.0; p = 0.011), baseline LV end-systolic
      volume (p = 0.023), and baseline LV ejection fraction (p = 0.034). In the
      bivariate Cox analysis, an addition of the paradoxical decrease in LVSV
      significantly enhanced the predictive power of all other univariate predictors.
      CONCLUSIONS: Heart failure patients with LV systolic dysfunction on the
      descending limb of the Starling curve can be recognized by the paradoxical
      decrease in LVSV despite PLL, and the prognostic predicting power is additive to
      the other traditional echocardiographic predictors. Also, our results suggest
      that functional mitral regurgitation is an important reason for the descending
      limb of the Starling curve, which is clinically recognized as the pre-load
      induced decrease in forward LVSV.

PMID- 27865721
TI  - New Concepts in an Old Disease: Exercise Intolerance in Moderate Mitral Stenosis.

PMID- 27865722
TI  - Effect of Sex and Sporting Discipline on LV Adaptation to Exercise.
AB  - OBJECTIVES: This study sought to investigate the effect of different types of
      exercise on left ventricular (LV) geometry in a large group of female and male
      athletes. BACKGROUND: Studies assessing cardiac adaptation in female and male
      athletes indicate that female athletes reveal smaller increases in LV wall
      thickness and cavity size compared with male athletes. However, data on sex
      specific changes in LV geometry in athletes are scarce. METHODS: A total of 1,083
      healthy, elite, white athletes (41% female; mean age 21.8 +/- 5.7 years) assessed
      with electrocardiogram and echocardiogram were considered. LV geometry was
      classified into 4 groups according to relative wall thickness (RWT) and left
      ventricular mass (LVM) as per European and American Society of Echocardiography
      guidelines: normal (normal LVM/normal RWT), concentric hypertrophy (increased
      LVM/increased RWT), eccentric hypertrophy (increased LVM/normal RWT), and
      concentric remodeling (normal LVM/increased RWT). RESULTS: Athletes were engaged
      in 40 different sporting disciplines with similar participation rates with
      respect to the type of exercise between females and males. Females exhibited
      lower LVM (83 +/- 17 g/m2 vs. 101 +/- 21 g/m2; p < 0.001) and RWT (0.35 +/- 0.05
      vs. 0.36 +/- 0.05; p < 0.001) compared with male athletes. Females also
      demonstrated lower absolute LV dimensions (49 +/- 4 mm vs. 54 +/- 5 mm; p <
      0.001) but following correction for body surface area, the indexed LV dimensions
      were greater in females (28.6 +/- 2.7 mm/m2 vs. 27.2 +/- 2.7 mm/m2; p < 0.001).
      Most athletes showed normal LV geometry. A greater proportion of females
      competing in dynamic sport exhibited eccentric hypertrophy compared with males
      (22% vs. 14%; p < 0.001). In this subgroup only 4% of females compared with 15%
      of males demonstrated concentric hypertrophy/remodeling (p < 0.001). CONCLUSIONS:
      Highly trained athletes generally show normal LV geometry; however, female
      athletes participating in dynamic sport often exhibit eccentric hypertrophy.
      Although concentric remodeling or hypertrophy in male athletes engaged in dynamic
      sport is relatively common, it is rare in female athletes and may be a marker of
      disease in a symptomatic athlete.

PMID- 27865724
TI  - Leg Lifting in HFrEF, Frank-Starling, and Mitral Regurgitation.

PMID- 27865723
TI  - Mechanisms of Effort Intolerance in Patients With Rheumatic Mitral Stenosis:
      Combined Echocardiography and Cardiopulmonary Stress Protocol.
AB  - OBJECTIVES: This study sought to evaluate mechanisms of effort intolerance in
      patients with rheumatic mitral stenosis (MS). BACKGROUND: Combined stress
      echocardiography and cardiopulmonary testing allows assessment of cardiac
      function, hemodynamics, and oxygen extraction (A-Vo2 difference). METHODS: Using
      semirecumbent bicycle exercise, 20 patients with rheumatic MS (valve area 1.36 +/
      0.4 cm2) were compared to 20 control subjects at 4 pre-defined activity stages
      (rest, unloaded, anaerobic threshold, and peak). Various echocardiographic
      parameters (left ventricular volumes, ejection fraction, stroke volume, mitral
      valve gradient, mitral valve area, tissue s' and e') and ventilatory parameters
      (peak oxygen consumption [Vo2] and A-Vo2 difference) were measured during 8 to 12
      min of graded exercise. RESULTS: Comparing patients with MS to control subjects,
      significant differences (both between groups and for group by time interaction)
      were seen in multiple parameters (heart rate, stroke volume, end-diastolic
      volume, ejection fraction, s', e', Vo2, and tidal volume). Exercise responses
      were all attenuated compared to control subjects. Comparing patients with MS and
      poor exercise tolerance (<80% of expected) to other subjects with MS, we found
      attenuated increases in tidal volume (p = 0.0003), heart rate (p = 0.0009), and
      mitral area (p = 0.04) in the poor exercise tolerance group. These patients also
      displayed different end-diastolic volume behavior over time (group by time
      interaction p = 0.05). In multivariable analysis, peak heart rate response (p =
      0.01), tidal volume response (p = 0.0001), and peak A-Vo2 difference (p = 0.03)
      were the only independent predictors of exercise capacity in patients with MS;
      systolic pulmonary pressure, mitral valve gradient, and mitral valve area were
      not. CONCLUSIONS: In patients with rheumatic MS, exercise intolerance is
      predominantly the result of restrictive lung function, chronotropic incompetence,
      limited stroke volume reserve, and peripheral factors, and not simply impaired
      valvular function. Combined stress echocardiography and cardiopulmonary testing
      can be helpful in determining mechanisms of exercise intolerance in patients with
      MS.

PMID- 27865726
TI  - [Falls in less than one year-old infants: Management in the emergency
      department].
AB  - OBJECTIVES: A study was performed in order to describe injuries associated with
      falls in children aged <1 year who attended the emergency department. The
      approaches used were examined, as well as the factors associated with the greater
      use of these approaches, and the management of the patient. PATIENTS AND METHODS:
      This was a multicentre, descriptive and analytical study that included all
      patients aged <1 year who had experienced a fall for which they attended the
      emergency departments of one of 8 Spanish Hospitals belonging to the
      "Unintentional Paediatric Injury Working Group" of the Spanish Paediatric
      Society. A record was made of the data regarding the visit, circumstances before
      arrival at the hospital, injuries observed, and the diagnostic and therapeutic
      approaches used. RESULTS: A total of 1022 patients had experienced falls, that
      is, 0.35% of the emergencies attended in the study hospitals (95% CI, 0,348
      0,352). The most commonly affected part was the head (58%). Cranial radiography
      was ordered in 31.8% of cases, and was associated with the presence of bruising
      or signs of fracture on examination (P<.001), falls from heights >100cm (P<.001),
      and age <3 months (P=.004). Minor head injury was the most common finding
      (85.6%), followed by fractures, especially cranial fractures (7.1%), which were
      associated with bruising or signs of fracture on examination (P<.001), and age <3
      months (P<.001). Six percent of the patients required admission to hospital. The
      risk factors for hospital admission in this group were falls from heights >50cm
      and age <3 months. CONCLUSIONS: Injuries after falls in infants aged <1 year are
      commonly due to head trauma and frequently require additional diagnostic tests.

PMID- 27865725
TI  - Cardiac CTA for Evaluation of Prosthetic Valve Dysfunction.

PMID- 27865727
TI  - [Epidemiology of patients hospitalised due to bronchiolitis in the south of
      Europe: Analysis of the epidemics, 2010-2015].
AB  - INTRODUCTION: The renewal of clinical practice guidelines on acute bronchiolitis
      (AB) requires the re-assessment of the consequences of their implementation. An
      update is presented on the main clinical and epidemiological variables in
      patients hospitalised due to AB in Southern Europe and an analysis made of the
      causes associated with longer hospital stay. PATIENTS AND METHOD: A retrospective
      study was conducted on patients admitted to hospital due to AB during 5 epidemics
      (2010-2015), with an analysis of the major clinical and epidemiological
      variables. A logistic regression analysis was performed on the factors associated
      with a longer hospital stay. RESULTS: The beginning of the epidemic occurred
      between the 4th week of September and the 3rd week of October. Of those children
      under 2 years (42,530), 15.21% (6,468 patients) attended paediatric emergency
      department due to having AB, and 2.36% (1,006 patients) were admitted. Of these,
      18.5% of were premature, 12.2% had a birth weight <2,300g, 21.1% were younger
      than 1 month, 10.8% consulted for associated apnoea, 31.1% had an intake <50%,
      and 13.1% had bacterial superinfection. These factors were independently
      associated with prolonged stay. The median length of stay was 5 days, and 8.5% of
      cases were admitted to a paediatric intensive care unit (PICU). CONCLUSIONS: The
      beginning of the bronchiolitis epidemic showed a variability of up to 4 weeks in
      this region. Five years after implementing the new guidelines, the incidence of
      admissions was approximately 2.3%, and appeared stable compared to previous
      studies. The mean age of the patients decreased to 2.4 months, although with a
      similar proportion of PICU admissions of 8.5%. Independent factors associated
      with prolonged stay were: low birth weight, age less than one month, apnoea prior
      to-admission, intake of less than 50%, and severe bacterial superinfection.
      Respiratory bacterial infection exceeded the prevalence of urinary tract
      infection.

PMID- 27865728
TI  - The Prevalence and Demographic Associations of Presenting Near-Vision Impairment
      Among Adults Living in the United States.
AB  - PURPOSE: To estimate prevalence of presenting near-vision impairment (PNVI) among
      people aged >=50 years in the United States (US) and examine associations with
      sociodemographic characteristics. DESIGN: Cross-sectional study. METHODS: A total
      of 11 016 of 12 781 (88.5%) US adults aged >=50 years participated in the
      National Health and Nutrition Examination Survey (NHANES) between 1999 and 2008
      with recorded near visual acuity. PNVI was defined as presenting near vision
      worse than 20/40; functional near-vision impairment (FNVI) was defined as at
      least "moderate difficulty" with either reading newsprint or near work.
      Prevalence of PNVI and FNVI were estimated accounting for National Health and
      Nutrition Examination Survey multistage probability sampling design.
      Multivariable regression models were used to determine sociodemographic
      characteristics associated with PNVI. RESULTS: A total of 13.6% of participants
      had PNVI, with 25.9% reporting concurrent FNVI. Higher odds of PNVI was
      associated with nonwhite race, older age, male sex, less than high school
      education, lack of private health insurance, income less than poverty level,
      lacking/not using near-vision correction at time of examination, and impaired
      distance vision. Although the majority of participants with PNVI (82.9%) had
      normal distance vision or uncorrected refractive error, less than half (46.1%)
      used near-vision correction. Not using near correction was associated with
      nonwhite race, younger age, male sex, and lack of access to health care.
      CONCLUSIONS: Approximately 1 in 8 Americans aged >=50 years have PNVI, with 1 in
      4 reporting concurrent FNVI. Demographic factors shown to be important in access
      to eye care likely influence PNVI and utilization of near-vision correction in
      the US. As the majority of PNVI is likely correctable with spectacles, allocation
      of resources to provide corrective lenses to those in need likely has great
      public health implications.

PMID- 27865729
TI  - Improving the efficiency of dissolved oxygen control using an on-line control
      system based on a genetic algorithm evolving FWNN software sensor.
AB  - This work proposes an on-line hybrid intelligent control system based on a
      genetic algorithm (GA) evolving fuzzy wavelet neural network software sensor to
      control dissolved oxygen (DO) in an anaerobic/anoxic/oxic process for treating
      papermaking wastewater. With the self-learning and memory abilities of neural
      network, handling the uncertainty capacity of fuzzy logic, analyzing local detail
      superiority of wavelet transform and global search of GA, this proposed control
      system can extract the dynamic behavior and complex interrelationships between
      various operation variables. The results indicate that the reasonable forecasting
      and control performances were achieved with optimal DO, and the effluent quality
      was stable at and below the desired values in real time. Our proposed hybrid
      approach proved to be a robust and effective DO control tool, attaining not only
      adequate effluent quality but also minimizing the demand for energy, and is
      easily integrated into a global monitoring system for purposes of cost
      management.

PMID- 27865730
TI  - Overview of the state of the art of constructed wetlands for decentralized
      wastewater management in Brazil.
AB  - Conventional wastewater treatment plants (WWTPs) commonly require large capital
      investments as well as operation and maintenance costs. Constructed wetlands
      (CWs) appear as a cost-effective treatment, since they can remove a broad range
      of contaminants by a combination of physical, chemical and biological processes
      with a low cost. Therefore, CWs can be successfully applied for decentralized
      wastewater treatment in regions with low population density and/or with large
      land availability as Brazil. The present work provides a review of thirty nine
      studies developed on CWs implemented in Brazil to remove wastewater contaminants.
      Brazil current sanitation data is also considered to evaluate the potential role
      of CWs as decentralized wastewater treatment. Performance of CWs was evaluated
      according to (i) type of wetland system, (ii) different support matrix (iii)
      vegetation species and (iv) removal efficiency of chemical oxygen demand (COD),
      biological oxygen demand (BOD5), nitrogen (N), and phosphorus (P). The reviewed
      CWs in overall presented good efficiencies, whereas H-CWs achieved the highest
      removals for P, while the higher results for N were attained on VF-CW and for COD
      and BOD5 on HF-CW. Therefore, was concluded that CWs are an interesting solution
      for decentralized wastewater treatment in Brazil since it has warm temperatures,
      extensive radiation hours and available land. Additionally, the low percentage of
      population with access to the sewage network in the North and Northeast regions
      makes these systems especially suitable. Hence, the further implementation of CW
      is encouraged by the authors in regions with similar characteristics as Brazil.

PMID- 27865731
TI  - Physicochemical characterization, modelling and optimization of ultrasono
      assisted acid pretreatment of two Pennisetum sp. using Taguchi and artificial
      neural networking for enhanced delignification.
AB  - Acid as well as ultrasono-assisted acid pretreatment of lignocellulosic biomass
      of two Pennisetum sp.; Denanath grass (DG) and Hybrid Napier grass (HNG) have
      been investigated for enhanced delignification and maximum exposure of cellulose
      for production of bioethanol. Screening of pretreatment with different acids such
      as H2SO4, HCl, H3PO4 and H2NO3 were optimized for different temperature, soaking
      time and acid concentrations using Taguchi orthogonal array and the data obtained
      were statistically validated using artificial neural networking. HCl was found to
      be the most effective acid for pretreatment of both the Pennisetum sp. The
      optimized conditions of HCl pretreatment were acid concentration of 1% and 1.5%,
      soaking time 130 and 50 min and temperature 121  degrees C and 110  degrees C
      which yielded maximum delignification of 33.0% and 33.8% for DG and HNG
      respectively. Further ultrosono-assisted HCl pretreatment with a power supply of
      100 W, temperature of 353 K, and duty cycle of 70% has resulted in significantly
      higher delignification of 80.4% and 82.1% for both DG and HNG respectively than
      that of acid pretreatment. Investigation using SEM, FTIR and autofloresence
      microscopy for both acid and ultrasono-assisted acid pretreatment lignocellulosic
      biomass revealed conformational changes of pretreated lignocellulosic biomass
      with decreased lignin content and increased exposure of cellulose, with greater
      effectiveness in case of ultrasono assisted acid pretreatment condition.

PMID- 27865733
TI  - Systolic and diastolic unloading by mechanical support of the acute vs the
      chronic pressure overloaded right ventricle.
AB  - BACKGROUND: Right ventricular (RV) mechanical support is well described in cases
      of sudden increase in RV afterload. In cases of chronic RV pressure overload
      (e.g., pulmonary arterial hypertension), it has rarely been described. METHODS:
      The pulmonary artery was banded in 18 sheep. In the acute group (n = 9), we
      immediately implanted a Synergy Pocket Micro-Pump. Blood was withdrawn from the
      right atrium to the pulmonary artery. In the chronic group (n = 9), this pump was
      implanted 8 weeks after banding. Hemodynamics and pressure-volume loops were
      recorded before and 15 minutes after pump activation. RESULTS: Low-flow RV
      mechanical support significantly improved arterial blood pressure in both groups,
      but cardiac output only in the acute group. Intrinsic RV contractility was not
      affected. The RV contribution to the total right-sided cardiac output was 54% +/-
      8 in the acute group vs 10% +/- 13 in the chronic group (p < 1.10-5), indicating
      a more profound unloading in the latter. Diastolic unloading (reflected by
      decreases in central venous pressure, end-diastolic pressure and volume, and
      ventricular capacitance) was successful in both groups. Decreases in pressure
      volume area and RV peak pressure reflected successful systolic unloading only in
      the chronic group. CONCLUSIONS: Low-flow RV mechanical support improved arterial
      blood pressure in both conditions but caused a more profound unloading in the
      chronic group. Diastolic unloading was successful in both groups, but systolic
      unloading was successful only in the chronic group. The potential use of low-flow
      mechanical support for a chronic pressure overloaded right ventricle warrants
      further research to assess its long-term effects.

PMID- 27865732
TI  - PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management: The
      PREVENT multi-center study.
AB  - BACKGROUND: Recommended structured clinical practices including implant
      technique, anti-coagulation strategy, and pump speed management (PREVENT
      [PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management]
      recommendations) were developed to address risk of early (<3 months) pump
      thrombosis (PT) risk with HeartMate II (HMII; St. Jude Medical, Inc. [Thoratec
      Corporation], Pleasanton, CA). We prospectively assessed the HMII PT rate in the
      current era when participating centers adhered to the PREVENT recommendations.
      METHODS: PREVENT was a prospective, multi-center, single-arm, non-randomized
      study of 300 patients implanted with HMII at 24 participating sites. Confirmed PT
      (any suspected PT confirmed visually and/or adjudicated by an independent
      assessor) was evaluated at 3 months (primary end-point) and at 6 months after
      implantation. RESULTS: The population included 83% men (age 57 years +/- 13), 78%
      destination therapy, and 83% Interagency Registry for Mechanically Assisted
      Circulatory Support (INTERMACS) Profile 1-3. Primary end-point analysis showed a
      confirmed PT of 2.9% at 3 months and 4.8% at 6 months. Adherence to key
      recommendations included 78% to surgical recommendations, 95% to heparin
      bridging, and 79% to pump speeds >=9,000 RPMs (92% >8,600 RPMs). Full adherence
      to implant techniques, heparin bridging, and pump speeds >=9,000 RPMs resulted in
      a significantly lower risk of PT (1.9% vs 8.9%; p < 0.01) and lower composite
      risk of suspected thrombosis, hemolysis, and ischemic stroke (5.7% vs 17.7%; p <
      0.01) at 6 months. CONCLUSIONS: Adoption of all components of a structured
      surgical implant technique and clinical management strategy (PREVENT
      recommendations) is associated with low rates of confirmed PT.

PMID- 27865734
TI  - Vascular endothelial growth factor A is associated with the subsequent
      development of moderate or severe cardiac allograft vasculopathy in pediatric
      heart transplant recipients.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the leading cause of chronic
      allograft loss after pediatric heart transplantation. We hypothesized that
      biomarkers of endothelial injury and repair would predict CAV development in
      pediatric heart transplant recipients. METHODS: Blood was collected from
      pediatric heart transplant recipients at the time of routine annual coronary
      angiography, and the concentrations of 13 angiogenesis-related molecules were
      determined. The primary end point was the presence of moderate or severe CAV by
      angiography during a 5-year follow-up period. RESULTS: The study enrolled 48
      recipients (57% male) with a median age of 15.5 years (range, 2-22 years) and
      median time post-transplant of 5.8 years (range, 2-15 years). Eight recipients
      developed moderate/severe CAV at a median follow-up of 4.7 years, of whom 3 died,
      3 underwent retransplantation, 1 had a myocardial infarction, and 1 was listed
      for retransplantation. Clinical characteristics associated with the development
      of moderate/severe CAV included prednisone use at enrollment (p = 0.03) and
      positive recipient cytomegalovirus immunoglobulin G at the time of transplant (p
      = < 0.01). Multivariable Cox proportional hazards regression identified plasma
      vascular endothelial growth factor (VEGF)-A concentration greater than 90 pg/ml
      at the time of blood draw as a significant predictor of time to moderate or
      severe CAV (hazard ratio, 14.3; 95% confidence interval, 1.3-163). Receiver
      operating characteristic curve analysis demonstrated that VEGF-A shows moderate
      performance for association with the subsequent development of CAV (area under
      the curve, 0.77; 95% confidence interval, 0.61-0.92). CONCLUSIONS: VEGF-A levels
      in pediatric heart transplant recipients are associated with clinically important
      CAV progression within the subsequent 5 years.

PMID- 27865735
TI  - Impact of age on incidence and prevalence of moderate-to-severe cellular
      rejection detected by routine surveillance biopsy in pediatric heart
      transplantation.
AB  - BACKGROUND: The effect of age at transplant on rejection detected by routine
      surveillance biopsy (RSB) in pediatric heart transplant (HT) recipients is
      unknown. We hypothesized there would be low diagnostic yield and decreased
      prevalence of rejection detected on RSB in infants (age <1 year) when compared
      with children (age 1 to 9 years) and adolescents (age 10 to 18 years). METHODS:
      We utilized Pediatric Heart Transplant Study (PHTS) data from 2010 to 2013 to
      analyze moderate-to-severe (ISHLT Grade 2R/3R) cellular rejection (MSR) detected
      only on RSB (RSBMSR). RESULTS: RSB detected 280 of 343 (81.6%) episodes of MSR.
      RSBMSR was detected in all age groups even >5 years after HT. Infant RSBMSR had a
      greater proportion (p = 0.0025) occurring >5 years after HT (39.2 vs 18.4 vs
      10.8%) and a lower proportion (p = 0.0009) occurring in the first year after HT
      (25.5 vs 60.6 vs 51.7%) compared with children and adolescents, respectively.
      Freedom from RSBMSR was 87 +/- 7% in infants, 76 +/- 6% in children and 73 +/- 7%
      in adolescents 4 years after HT. In 1-year survivors who had RSBMSR in the first
      year after HT, the risk of RSBMSR occurring in Years 2 to 4 was significantly (p
      < 0.0001) greater than patients without RSBMSR in the first year (hazard ratio
      21.28, 95% confidence interval 10.87 to 41.66), regardless of recipient age.
      CONCLUSIONS: RSBMSR exists in all age groups after pediatric HT with long-term
      follow-up. The prevalence in infant recipients is highest >5 years after HT.
      Those with RSBMSR in the first year after HT are at a high risk for recurrent
      rejection regardless of age at HT.

PMID- 27865737
TI  - Echocardiographic assessment of feline false tendons and their relationship with
      focal thickening of the left ventricle.
AB  - BACKGROUND: False tendons (FTs) are string-like structures in the left ventricle.
      A FT might produce focal thickening at its insertion region of the left
      ventricle, which could be mistaken for focal hypertrophic cardiomyopathy.
      OBJECTIVES: To perform a prospective, echocardiographic follow-up examination of
      feline FTs and compare the wall thickness at the FT insertion region and a normal
      region without FTs at both examinations. ANIMALS: One hundred twenty-eight cats
      with one or multiple FTs without other cardiac abnormalities or systemic disease.
      METHODS: Measurements of the interventricular septum at end-diastole at a region
      with and without FT insertion were performed using two-dimensional
      echocardiography at both examinations and compared statistically using a
      Student's t-test. RESULTS: The follow-up interval ranged from 5 to 110 months
      (mean, 33 months). Myocardial wall segments with FT insertions were significantly
      thicker compared with neighboring wall regions in the long axis, but not in the
      short-axis views obtained. Comparing the wall thickness of follow-up examinations
      with the initial examination, revealed a significant growth of both FT and non-FT
      segments. However, differences in growth between the FT region and region without
      FTs were not statistically different. CONCLUSIONS AND CLINICAL IMPORTANCE: Many
      normal cats have FTs, associated with focal thickening compared with neighboring
      regions. This thickening can increase over time, proportionate to growth in other
      (non-FT) segments. The association of such thickening with an FT and the absence
      of disproportionate growth in this segment over time suggests that these segments
      are simply thicker related to FT insertion.

PMID- 27865738
TI  - Evaluation of the modified carbapenem inactivation method and sodium
      mercaptoacetate-combination method for the detection of metallo-beta-lactamase
      production by carbapenemase-producing Enterobacteriaceae.
AB  - We evaluated the effectiveness of carbapenem inactivation method (CIM) and
      modified CIM (mCIM). Our results indicated that mCIM with 4h incubation improved
      sensitivity and specificity for detecting carbapenemase-producing
      Enterobacteriaceae compared to CIM. Additionally, we developed a sodium
      mercaptoacetate-combination method (SMA-mCIM) to detect metallo-beta-lactamase
      (MBL) with high sensitivity and specificity.

PMID- 27865739
TI  - Shaken or stirred?: Comparison of methods for dispersion of Mycoplasma pneumoniae
      aggregates for persistence in vivo.
AB  - BACKGROUND: Mycoplasma pneumoniae (Mpn), one of the smallest self-replicating
      prokaryotes, is known to readily adhere to host cells and to form aggregates in
      suspension. Having only one cell membrane and no cell wall, mycoplasmas present
      questions as to optimal aggregate disruption method while minimizing cell death
      in vitro. We compared conventional vortex mixing with other methods for
      disruption of bacterial aggregates and for its effect on cell viability. METHODS:
      Strain UAB PO1, a clinical Mpn isolate, was dispersed using a conventional vortex
      mixer with or without nonionic detergent (0.1% and 0.01% Tween-20), a probe-type
      ultrasonicator, or repeated passage through a 27-gauge needle. The resulting
      suspensions were assayed for recoverable colony-forming units (CFU). Flow
      cytometric assays were carried out to examine particle size and membrane
      integrity with the transmembrane potential dye DiBAC4. Wet Scanning Transmission
      Electron Microscopy (Wet-STEM) was performed for high resolution imaging of the
      resultant cell suspensions. Additional Mpn strains and other human mollicute
      species were assayed in a similar manner. Mice were infected with either vortexed
      or sonicated UAB PO1 and bacterial persistence was examined via Mpn-specific 16S
      qPCR. RESULTS: Comparison between dispersion methods showed a 10-fold enrichment
      of recoverable Mpn CFU with sonication compared to other methods. Time-course
      analysis showed significantly lower bacterial CFU with vortexing compared to
      sonication at all time points. Flow cytometric analysis showed increased cellular
      membrane damage via DiBAC4 staining in sonicated suspensions, but a decreased
      particle size. Wet-STEM imaging showed markedly improved dispersion with
      sonication compared to conventional vortex treatment, and surprisingly vortexing
      for 30s produced up to a 100-fold drop in CFU. Results similar to UAB PO1 were
      obtained with three additional Mpn strains and other Mollicutes species, although
      they exhibited differential susceptibilities to disaggregation by sonication.
      Finally, increased persistence of the organism in a mouse model of infection was
      observed using sonicated suspensions for initial infection. CONCLUSIONS:
      Sonication is superior to vortexing with or without nonionic detergent or
      repeated 27-gauge needle passage for dispersion of Mpn aggregates while
      preserving cell viability. Preparation of Mpn suspensions for in vivo experiments
      is best accomplished using brief sonication due to the dramatic increase in CFU
      produced by sonication. Dispersion methods may affect the final experimental
      results and should be an important consideration for future research involving
      mycoplasma species.

PMID- 27865736
TI  - iPS-derived neural progenitor cells from PPMS patients reveal defect in myelin
      injury response.
AB  - Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease
      of the central nervous system (CNS) currently lacking any effective treatment.
      Promoting endogenous brain repair offers a potential strategy to halt and
      possibly restore neurologic function in PPMS. To understand how the
      microenvironment within white matter lesions plays a role in repair we have
      focused on neural progenitor cells (NPCs) since these are found in lesions in
      PPMS and have been found to influence oligodendrocyte progenitor cell maturation
      (OPCs). To better understand the cellular nature of NPCs in PPMS we developed iPS
      cells from blood samples of PPMS patients and age matched non-disease spouse or
      blood relative controls. Using these iPS cell lines we determined that the NPCs
      from PPMS cases provided no neuroprotection against active CNS demyelination
      compared to NPCs from control iPS lines which were capable of completely
      preventing injury. Conditioned media (CM) from PPMS NPCs provides no protection
      to OPCs and prevents maturation of OPCs into oligodendrocytes in vitro. We also
      found that CM from PPMS iPS NPCs elicited patient-specific differences in the
      response to compounds that should foster oligodendrocyte (OL) maturation.
      Together, these data establish a new model for understanding the nature of
      myelination defects in PPMS which may lead to novel targeted approaches for
      preventing demyelination in these patients.

PMID- 27865742
TI  - Internal rectal prolapse: Definition, assessment and management in 2016.
AB  - Internal rectal prolapse (IRP) is a well-recognized pelvic floor disorder mainly
      seen during defecatory straining. The symptomatic expression of IRP is complex,
      encompassing fecal continence (56%) and/or evacuation disorders (85%). IRP cannot
      be characterized easily by clinical examination alone and the emergence of
      dynamic defecography (especially MRI) has allowed a better comprehension of its
      pathophysiology and led to the proposition of a severity score (Oxford score)
      that can guide management. Decision for surgical management should be
      multidisciplinary, discussed after a complete work-up, and only after medical
      treatment has failed. Information should be provided to the patient, outlining
      the goals of treatment, the potential complications and results. Stapled trans
      anal rectal resection (STARR) has been considered as the gold standard for IRP
      treatment. However, inconsistent results (failure observed in up to 20% of cases,
      and fecal incontinence occurring in up to 25% of patients at one year) have led
      to a decrease in its indications. Laparoscopic ventral mesh rectopexy has
      substantial advantages in solving the functional problems due to IRP (efficacy on
      evacuation and resolution of continence symptoms in 65-92%, and 73-97% of
      patients, respectively) and is currently considered as the gold standard therapy
      for IRP once the decision to operate has been made.

PMID- 27865741
TI  - Seasonal Population Movements and the Surveillance and Control of Infectious
      Diseases.
AB  - National policies designed to control infectious diseases should allocate
      resources for interventions based on regional estimates of disease burden from
      surveillance systems. For many infectious diseases, however, there is pronounced
      seasonal variation in incidence. Policy-makers must routinely manage a public
      health response to these seasonal fluctuations with limited understanding of
      their underlying causes. Two complementary and poorly described drivers of
      seasonal disease incidence are the mobility and aggregation of human populations,
      which spark outbreaks and sustain transmission, respectively, and may both
      exhibit distinct seasonal variations. Here we highlight the key challenges that
      seasonal migration creates when monitoring and controlling infectious diseases.
      We discuss the potential of new data sources in accounting for seasonal
      population movements in dynamic risk mapping strategies.

PMID- 27865743
TI  - A smart way to reconstruct the middle hepatic vein during major hepatectomy.

PMID- 27865740
TI  - Sm-p80-Based Schistosomiasis Vaccine: Preparation for Human Clinical Trials.
AB  - Mass antiparasitic drug administration programs and other control strategies have
      made important contributions in reducing the global prevalence of helminths.
      Schistosomiasis, however, continues to spread to new geographic areas. The advent
      of a viable vaccine and its deployment, coupled with existing control efforts, is
      expected to make significant headway towards sustained schistosomiasis control.
      In 2016, Science ranked the schistosomiasis vaccine as one of the top 10 vaccines
      that needs to be urgently developed. A vaccine that is effective against
      geographically distinct forms of intestinal/hepatic and urinary disease is
      essential to make a meaningful impact in global reduction of the disease burden.
      In this opinion article, we focus on salient features of schistosomiasis vaccines
      in different phases of the clinical development pipeline and highlight the Sm-p80
      based vaccine which is now being prepared for human clinical trials.

PMID- 27865745
TI  - Movement artifacts mimicking a normal EEG background activity in a patient with
      anoxic brain injury.

PMID- 27865746
TI  - Serious complication of applying a laryngeal mask after a foreign body aspiration
      in an infant.

PMID- 27865744
TI  - Outcomes of sudden cardiac arrest in a state-wide integrated resuscitation
      program: Results from the Minnesota Resuscitation Consortium.
AB  - BACKGROUND: Despite many advances in resuscitation science the outcomes of sudden
      cardiac arrest (SCA) remain poor. The Minnesota Resuscitation Consortium (MRC) is
      a statewide integrated resuscitation program, established in 2011, to provide
      standardized, evidence-based resuscitation and post-resuscitation care. The
      objective of this study is to assess the outcomes of a state-wide integrated
      resuscitation program. METHODS: We examined the trends in resuscitation metrics
      and outcomes in Minnesota since 2011 and compared these to the results from the
      national Cardiac Arrest Registry to Enhance Survival (CARES) program. Since 2011
      MRC has expanded significantly providing service to >75% of Minnesota's
      population. RESULTS: A total of 5192 SCA occurred in counties covered by MRC from
      2011 to 2014. In this period, bystander cardiopulmonary resuscitation (CPR) and
      use of hypothermia, automatic CPR device and impedance threshold device increased
      significantly (p<0.0001 for all). Compared to CARES, SCA cases in Minnesota were
      more likely to be ventricular fibrillation (31% vs. 23%, p<0.0001) but less
      likely to receive bystander CPR (33% vs. 39%, p<0.0001). Survival to hospital
      discharge with good or moderate cerebral performance (12% vs. 8%, p<0.0001),
      survival in SCA with a shockable rhythm (Utstein survival) (38% vs. 33%,
      p=0.0003) and Utstein survival with bystander CPR (44% vs. 37%, p=0.003) were
      greater in Minnesota than CARES. CONCLUSIONS: State-wide integration of
      resuscitation services in Minnesota was feasible. Survival rate after cardiac
      arrest is greater in Minnesota compared to the mean survival rate in CARES.

PMID- 27865747
TI  - Impact of neighbourhood socio-economic status on bystander cardiopulmonary
      resuscitation in Paris.
AB  - BACKGROUND: No European data currently describe the relation between
      neighbourhood socio-economic status (SES) and rates of out-of-hospital cardiac
      arrest (OHCA) bystander cardiopulmonary resuscitation (CPR). This study aims to
      analyse this effect with a robust deprivation index. METHODS: Data about all OHCA
      in Paris were collected prospectively between 2000 and 2010. A geographical
      neighbourhood unit was assigned to each case. Median household income, and rates
      of blue-collar workers, unemployment, and adults without high school diplomas
      were selected as SES characteristics and used to classify neighbourhoods as low
      SES or higher SES. We analysed the relationship between neighbourhood SES
      characteristics and the probability of receiving bystander CPR. RESULTS: Of the
      4009 OHCA with mappable addresses recorded, 777 (19.4%) received bystander CPR.
      Compared to OHCA who did not receive bystander CPR, those receiving CPR were
      significantly more likely to have occurred in public locations, have had a
      witness to their OHCA, and not to have collapsed in a low SES neighbourhood, or
      in a neighbourhood with a median household income in the lowest quartile and with
      rates of no high school diplomas and blue-collar workers in the highest quartile.
      In the multilevel analyses, bystander CPR provision was significantly less
      frequent in low than in higher SES neighbourhoods (OR 0.85; 95% confidence
      interval [CI] 0.72-0.99). CONCLUSION: In the city of Paris, OHCA victims were
      less likely to receive bystander CPR in low SES neighbourhoods. These first
      European data are consistent with observations in North America and Asia.

PMID- 27865748
TI  - A novel reverse genetics system for production of infectious West Nile virus
      using homologous recombination in mammalian cells.
AB  - Reverse genetics systems facilitate investigation of many aspects of the life
      cycle and pathogenesis of viruses. However, genetic instability in Escherichia
      coli has hampered development of a reverse genetics system for West Nile virus
      (WNV). In this study, we developed a novel reverse genetics system for WNV based
      on homologous recombination in mammalian cells. Introduction of the DNA fragment
      coding for the WNV structural protein together with a DNA-based replicon resulted
      in the release of infectious WNV. The growth rate and plaque size of the
      recombinant virus were almost identical to those of the parent WNV. Furthermore,
      chimeric WNV was produced by introducing the DNA fragment coding for the
      structural protein and replicon plasmid derived from various strains. Here, we
      report development of a novel system that will facilitate research into WNV
      infection.

PMID- 27865750
TI  - Outcomes Following Radical Cystectomy for Plasmacytoid Urothelial Carcinoma:
      Defining the Need for Improved Local Cancer Control.
AB  - OBJECTIVE: To evaluate oncological outcomes after radical cystectomy (RC) in
      patients with plasmacytoid urothelial carcinoma (UC) and to compare survival to
      that in patients with pure UC of the bladder. MATERIALS AND METHODS: We
      identified 46 patients with plasmacytoid UC and 972 with pure UC who were treated
      with RC between 1980 and 2009. All pathologic specimens were re-reviewed by a
      single GU pathologist. Patients were matched 1:2 by age, gender, Eastern
      Cooperative Oncology Group performance status, pathologic tumor stage, and nodal
      status to patients with pure UC. Survival was estimated using the Kaplan-Meier
      method and compared with the log rank test. RESULTS: Patients with plasmacytoid
      UC were more likely to have extravesical disease (>=pT3) (83% vs 43%, P < .0001)
      and positive margins (31% vs 2.1%, P < .0001) than patients with pure UC.
      Plasmacytoid UC was associated with decreased overall survival (27% vs 45% at 5
      years, relative risk [RR] 1.4, P = .04), cancer-specific survival (36% vs 57% at
      5 years, RR 1.7, P = .01), and local recurrence-free survival (63% vs 81% at 5
      years, RR 2, P = .01). When patients with plasmacytoid UC were matched to those
      with pure UC, there were no significant differences in 5-year overall, cancer
      specific, and local or distant recurrence-free survival. CONCLUSION: Plasmacytoid
      UC is associated with a high rate of locally advanced disease and positive
      margins at RC, as well as increased local recurrence rates. Further research is
      necessary to delineate adjuvant or neoadjuvant treatment strategies to improve
      local cancer control of this rare subtype of UC.

PMID- 27865751
TI  - Feasibility of Long-term Tibial Nerve Stimulation Using a Multi-contact and
      Wirelessly Powered Neurostimulation System Implanted in Rats.
AB  - OBJECTIVE: Implant-driven tibial nerve stimulation therapy is an effective
      technique for treating overactive bladder. However, the monopolar lead design in
      the currently available implantable devices pose long-term therapeutic challenges
      in terms of efficiently and selectively delivering electrical pulses to the
      target. Hence, the purpose of this study was to (1) characterize the tibial nerve
      (TN) activation properties using a multi-contact implantable system and (2)
      evaluate the long-term stability of using such a neural interface in a
      preclinical model. MATERIALS AND METHODS: Ten adult Sprague-Dawley rats were used
      in this study. An implantable pulse generator was surgically inserted in the
      lower back region. The lead wire with 4 active electrodes was placed in parallel
      with the TN. The threshold for activating the TN was confirmed via movement of
      the hallux or toes as well as the foot EMG. The TN activation threshold was
      assessed biweekly, over a period of 12 weeks. RESULTS: Channel 1 exhibited the
      lowest motor threshold at T0 (mean = 0.58 +/- 0.10 mA). A notable increase in
      motor twitch intensity was observed during the first test session (2 weeks)
      following surgical implantation (75.8 +/- 30.5%, channel 1). Among the 10 rats
      tested, 8 rats successfully completed the 3-month study. CONCLUSION: Results from
      this study demonstrate the long-term feasibility of achieving tibial nerve
      stimulation with a multi-contact implantable device in a preclinical model.
      Future studies are warranted to assess the effects of using such a wirelessly
      powered system for treating lower urinary tract symptoms in patients.

PMID- 27865752
TI  - Reconstruction of Massive Localized Lymphedema of the Scrotum: Results,
      Complications, and Quality of Life Improvements.
AB  - OBJECTIVE: To review the surgical technique, outcomes, and complications of
      surgical excision of massive localized lymphedema (MLL) of the scrotum, and to
      determine changes in weight and quality of life (QOL) after excision. METHODS: A
      retrospective review was performed for all patients who have undergone excision
      of MLL of the scrotum at our institution between 2008 and 2014. Standard baseline
      characteristics, complications, pre- and postoperative weight, and QOL data were
      recorded. RESULTS: Eleven patients were included, with a mean follow-up of 26
      months after surgery. The mean preoperative body mass index was 60, and the mean
      weight of resected tissue was 21 kg. No patient required an orchiectomy for
      completion of the resection. Skin grafting was performed in 1 patient, and the
      rest were closed primarily. Wound complications were common but generally managed
      successfully with local wound care. At the time of most recent follow-up, most
      patients had actually gained weight since surgery (mean weight change of +5.2
      kg). However, QOL scores improved across all domains, and overall QOL improved
      from a mean of 1.3 preoperatively to 7.7 postoperatively (where 1 is poor, and 10
      is excellent). CONCLUSION: Surgical treatment of MLL of the scrotum can be
      performed successfully for masses even up to 61 kg (134 lbs). Short-term wound
      complications are common, but subjective QOL scores improve dramatically. Despite
      expectations, most patients gained weight after mass removal, which indicates
      that they would benefit from a comprehensive weight loss plan that includes, but
      is not limited to, scrotal surgery.

PMID- 27865749
TI  - In vitro functional assessment of natural HIV-1 group M Vpu sequences using a
      universal priming approach.
AB  - The HIV-1 accessory protein Vpu exhibits high inter- and intra- subtype genetic
      diversity that may influence Vpu function and possibly contribute to HIV-1
      pathogenesis. However, scalable methods to evaluate genotype/phenotype
      relationships in natural Vpu sequences are limited, particularly those expressing
      the protein in CD4+ T-cells, the natural target of HIV-1 infection. A major
      impediment to assay scalability is the extensive genetic diversity within, and
      immediately upstream of, Vpu's initial 5' coding region, which has necessitated
      the design of oligonucleotide primers specific for each individual HIV-1 isolate
      (or subtype). To address this, we developed two universal forward primers,
      located in relatively conserved regions 38 and 90 bases upstream of Vpu, and a
      single universal reverse primer downstream of Vpu, which are predicted to cover
      the vast majority of global HIV-1 group M sequence diversity. We show that
      inclusion of up to 90 upstream bases of HIV-1 genomic sequence does not
      significantly influence in vitro Vpu expression or function when a Rev/Rev
      Response Element (RRE)-dependent expression system is used. We further assess the
      function of four diverse HIV-1 Vpu sequences, revealing reproducible and
      significant differences between them. Our approach represents a scalable option
      to measure the in vitro function of genetically diverse natural Vpu isolates in a
      CD4+ T-cell line.

PMID- 27865753
TI  - Development and Validation of the Self-Efficacy Regarding Vaginal Birth Scale.
AB  - OBJECTIVES: The purpose of this study was to develop a scale to measure self
      efficacy regarding a vaginal birth (SEVB) during pregnancy and to assess its
      reliability and validity among nulliparous Chinese women. DESIGN: A panel study.
      SETTING: Five hospitals in Northern Taiwan. PARTICIPANTS: The analysis included
      700 (second trimester), 637 (third trimester), and 585 (before birth) women who
      did not have medical indications for cesarean births at the indicated time
      points. METHODS: The SEVB scale was used to measure the level of confidence in
      ability to carry the pregnancy to term and give birth vaginally. The scale
      included nine items, and each was scored on a numeric rating scale from 0 to 10.
      A higher score indicated a higher level of self-efficacy. RESULTS: Factor
      analysis confirmed the one-factor structure, which explained 62.77% and 67.08% of
      the variance, with Cronbach's alphas for the scale of 0.93 and 0.94 during the
      second and third trimesters, respectively. The test-retest reliability was 0.73
      as determined by the intraclass correlation coefficient. Contrasted group
      validity supported that those women who preferred cesarean births had
      significantly lower SEVB scores than women who preferred vaginal births during
      the second and third trimesters. Those women who tried vaginal births had higher
      SEVB scores than women who had cesareans without trying vaginal births.
      CONCLUSION: The scale showed acceptable reliability and validity. Health
      professionals could use the scale to screen women with low self-efficacy during
      pregnancy and provide appropriate intervention to increase their willingness to
      try vaginal births.

PMID- 27865754
TI  - Perinatal Nurse Home Visiting Referral Patterns Among Women With Diabetes and
      Hypertension in Philadelphia.
AB  - OBJECTIVE: To examine access to perinatal nurse home visiting services for high
      risk pregnant women who have diabetes or hypertension. DESIGN: Secondary data
      analysis. SETTING: Philadelphia, PA. PARTICIPANTS: Pregnant women who had a live
      birth during 2012 and those referred to a community-based agency for perinatal
      nurse home visiting because of their diagnosis of diabetes or hypertension.
      METHODS: Access to services was measured by examining referral information
      (dosage, diagnosis, gestational age at time of referral, and insurance type)
      retrieved from administrative logs of the community-based organization that
      provides perinatal home visiting to high-risk pregnant women. The population
      based prevalence rates of hypertension and diabetes were calculated from birth
      record data provided by the Philadelphia Department of Public Health. RESULTS:
      During 2012, 595 pregnant women were referred for perinatal nurse home visiting
      services. The mean gestational age when referred for services was 24.9 weeks
      (standard deviation = 8.5) with a mean number of 8.8 authorized visits (standard
      deviation = 8). Associated with more authorized visits was having Medicaid as the
      insurance type and medical diagnoses that included hypertension (p < .01).
      Philadelphia prevalence rates for diabetes and hypertension varied by race and
      ethnicity (p < .001); Asian mothers had the greatest rates for diabetes and Black
      mothers the greatest rates for hypertension. CONCLUSION: Various models of home
      visiting programs exist to improve maternal and child health outcomes. Because
      maternal morbidity and mortality rates are rising in the United States, further
      research about perinatal nurse home visiting programs for pregnant women with
      diabetes and hypertension is warranted.

PMID- 27865755
TI  - Corrigendum to "Fc-gamma receptors are not involved in cartilage damage during
      experimental osteoarthritis" [Osteoarthritis Cartilage 23 (2015) 1221-1225].

PMID- 27865757
TI  - Guilt, or guilt by association? Insulin therapy in type 2 diabetes and death.

PMID- 27865756
TI  - Association of insulin dosage with mortality or major adverse cardiovascular
      events: a retrospective cohort study.
AB  - BACKGROUND: Existing studies have shown conflicting evidence regarding the safety
      of exogenous insulin therapy in patients with type 2 diabetes. In particular,
      observational studies have reported an increased risk of death and cardiovascular
      disease among users of higher versus lower doses of insulin. We aimed to quantify
      the association between increasing dosage of insulin exposure and death and
      cardiovascular events, while taking into account time-dependent confounding and
      mediation that might have biased previous studies. METHODS: We did a cohort study
      using primary care records from the UK-based Clinical Practice Research Datalink
      (CPRD). New users of metformin monotherapy were identified in the period between
      Jan 1, 2001, and Dec 31, 2012. We then identified those in this group with a new
      prescription for insulin. Insulin exposure was categorised into groups according
      to the mean dose (units) per day within 180-day time segments throughout each
      patient's follow-up. Relative differences in mortality and major adverse
      cardiovascular events (non-fatal myocardial infarction, non-fatal stroke,
      cardiovascular-related mortality) were assessed using conventional multivariable
      Cox proportional hazards models. Marginal structural models were then applied to
      reduce bias introduced by the time-dependent confounders affected by previous
      treatment. FINDINGS: We identified 165 308 adults with type 2 diabetes in the
      CPRD database. After applying our exclusion criteria, 6072 (mean age 60 years [SD
      12.5], 3281 [54%] men, mean HbA1c 8.5% [SD 1.75], and median follow-up 3.1 years
      [IQR 1.7-5.3) were new add-on insulin users and were included in the study
      cohort; 3599 were new add-on insulin users and were included in the subcohort
      linked to hospital records and death certificate information. Crude mortality
      rates were comparable between insulin dose groups; <25 units per day (46 per 1000
      person-years), 25 to <50 units per day (39 per 1000 person-years), 50 to <75
      units per day (27 per 1000 person-years), 75 to <100 units per day (34 per 1000
      person-years), and at least 100 units per day (32 per 1000 person-years; p>0.05
      for all; mean rate of 31 deaths per 1000 person-years [95% CI 29-33]). With
      adjustment for baseline covariates, mortality rates were higher for increasing
      insulin doses: less than 25 units per day [reference group]; 25 to <50 units per
      day, hazard ratio (HR) 1.41 [95% CI 1.12-1.78]; 50 to <75 units per day, 1.37
      [1.04-1.80]; 75 to <100 units per day, 1.85 [1.35-2.53]; and at least 100 units
      per day, 2.16 [1.58-2.93]. After applying marginal structural models, insulin
      dose was not associated with mortality in any group (p>0.1 for all).
      INTERPRETATION: In conventional multivariable regression analysis, higher insulin
      doses are associated with increased mortality after adjustment for baseline
      covariates. However, this effect seems to be confounded by time-dependent factors
      such as insulin exposure, glycaemic control, bodyweight gain, and the occurrence
      of cardiovascular and hypoglycaemic events. This study provides reassurance of
      the overall safety of insulin use in the treatment of type 2 diabetes and
      contributes to our understanding of the contrasting conclusions from non
      randomised and randomised studies regarding dose-dependent effects of insulin on
      cardiovascular events and mortality. FUNDING: Canadian Institutes of Health
      Research, Heart and Stroke Foundation of Canada, and the Newfoundland and
      Labrador Research and Development Corporation.

PMID- 27865759
TI  - miRNA-Coordinated Networks as Promising Therapeutic Targets for Acute Kidney
      Injury.
AB  - This commentary highlights the article by Wilflingseder et al that investigates
      the relationship between in vivo inhibition of miR-182 by antisense
      oligonucleotides and improved post-injury kidney function.

PMID- 27865758
TI  - Bone Morphogenetic Protein 2 and Transforming Growth Factor beta1 Inhibit the
      Expression of the Proinflammatory Cytokine IL-34 in Rheumatoid Arthritis Synovial
      Fibroblasts.
AB  - IL-34 is a proinflammatory cytokine implicated in rheumatoid arthritis (RA). The
      current study aimed to assess the IL-34 expression in response to two members of
      the transforming growth factor (TGF)-beta family, TGF-beta1 and bone
      morphogenetic protein (BMP)-2, in synovial fibroblasts from RA patients. IL-34,
      TGF-beta1, and BMP-2 productions were measured in patient synovial fluids by
      enzyme-linked immunosorbent assay. IL-34 mRNA levels were quantified by real-time
      quantitative PCR in human synovial fibroblasts and murine mesenchymal stem cells.
      Pharmacologic inhibitions were used to determine the involvement of activin
      receptor-like kinase 1 (ALK1) and ALK5 downstream TGF-beta1 and BMP-2. IL-34, TGF
      beta1, and BMP-2 were expressed in synovial fluids from RA patients. We found a
      significant correlation between IL-34 and TGF-beta1 expressions. Levels of both
      IL-34 and TGF-beta1 were thus correlated with the total leukocyte counts in the
      synovial fluids. TGF-beta1 and BMP-2 decreased IL-34 expression in the synovial
      fibroblasts or in murine mesenchymal stem cells in a dose- and time-dependent
      manner through ALK5 and ALK1 pathways, respectively. In addition, TGF-beta1 and
      BMP-2 antagonized tumor necrosis factor alpha-induced IL-34 gene expression. This
      work identifies TGF-beta1 and BMP-2 as potent inhibitors of IL-34 expression in
      RA synovial fibroblasts. These cytokines, as upstream inhibitors of IL-34, may
      thus contribute to antagonize inflammation and bone erosions in RA.

PMID- 27865760
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- 27865761
TI  - Pharmacist-led health-system approaches to reduce opioid overdose and death.

PMID- 27865763
TI  - Screening biological methods for laboratory scale stabilization of fine fraction
      from landfill mining.
AB  - Increasing interest for the landfill mining and the amount of fine fraction (FF)
      in landfills (40-70% (w/w) of landfill content) mean that sustainable treatment
      and utilization methods for FF are needed. For this study FF (<20mm) was mined
      from a municipal solid waste (MSW) landfill operated from 1967 to 1989. FF, which
      resembles soil, was stabilized in laboratory scale reactors in two phases: first,
      anaerobically for 101days and second, for 72days using four different methods:
      anaerobic with the addition of moisture (water) or inoculum (sewage sludge) and
      aerobic with continuous water washing, with, or without, bulking material. The
      aim was to evaluate the effect on the stability of mined FF, which has been
      rarely reported, and to study the quality and quantity of gas and leachate
      produced during the stabilization experiment. The study showed that aerobic
      treatment reduced respiration activity (final values 0.9-1.1mgO2/gTS) and
      residual methane potential (1.1LCH4/kgTS) better than anaerobic methods (1.8
      2.3mg O2/g TS and 1.3-2.4L CH4/kg TS, respectively). Bulking material mixed in FF
      in one aerobic reactor had no effect on the stability of FF. The benefit of
      anaerobic treatment was the production of methane, which could be utilized as
      energy. Even though the inoculum addition increased methane production from FF
      about 30%, but the methane production was still relatively low (in total 1.5-1.7L
      CH4/kg TS). Continuous water washing was essential to remove leachable organic
      matter and soluble nutrients from FF, while increasing the volume of leachate
      collected. In the aerobic treatment, nitrogen was oxidized into nitrite and
      nitrate and then washed out in the leachate. Both anaerobic and aerobic methods
      could be used for FF stabilization. The use of FF, in landscaping for example, is
      possible because its nutrient content (4gN/kg TS and 1g P/kg TS) can increase the
      nutrient content of soil, but this may have limitations due to the possible
      presence of heavy metal and other contaminants.

PMID- 27865765
TI  - Assessing Gametocyte Carriage in Treated Asymptomatic Falciparum Carriers in
      Africa.

PMID- 27865766
TI  - Inulin: A New Adjuvant With Unknown Mode of Action.

PMID- 27865762
TI  - Tumor-targeted nanomedicines for cancer theranostics.
AB  - Chemotherapeutic drugs have multiple drawbacks, including severe side effects and
      suboptimal therapeutic efficacy. Nanomedicines assist in improving the
      biodistribution and target accumulation of chemotherapeutic drugs, and are
      therefore able to enhance the balance between efficacy and toxicity. Multiple
      types of nanomedicines have been evaluated over the years, including liposomes,
      polymer-drug conjugates and polymeric micelles, which rely on strategies such as
      passive targeting, active targeting and triggered release for improved tumor
      directed drug delivery. Based on the notion that tumors and metastases are highly
      heterogeneous, it is important to integrate imaging properties in nanomedicine
      formulations in order to enable non-invasive and quantitative assessment of
      targeting efficiency. By allowing for patient pre-selection, such next generation
      nanotheranostics are useful for facilitating clinical translation and
      personalizing nanomedicine treatments.

PMID- 27865764
TI  - Phase 2a Randomized Clinical Trial: Safety and Post Hoc Analysis of Subretinal
      rAAV.sFLT-1 for Wet Age-related Macular Degeneration.
AB  - BACKGROUND: We present the results of a Phase 2a randomized controlled trial
      investigating the safety, and secondary endpoints of subretinal rAAV.sFLT-1 gene
      therapy in patients with active wet age-related macular degeneration (wAMD).
      METHODS: All patients (n=32), (ClinicalTrials.gov; NCT01494805), received
      ranibizumab injections at baseline and week 4, and thereafter according to
      prespecified criteria. Patients in the gene therapy group (n=21) received
      rAAV.sFLT-1 (1*1011vg). All patients were assessed every 4weeks to the week 52
      primary endpoint. FINDINGS: Ocular adverse events (AEs) in the rAAV.sFLT-1 group
      were mainly procedure related and self-resolved. All 11 phakic patients in the
      rAAV.sFLT-1 group showed progression of cataract following vitrectomy. No
      systemic safety signals were observed and none of the serious AEs were associated
      with rAAV.sFLT-1. AAV2 capsid was not detected and rAAV.sFLT-1 DNA was detected
      transiently in the tears of 13 patients. ELISPOT analysis did not identify any
      notable changes in T-cell response. In the rAAV.sFLT-1 group 12 patients had
      neutralizing antibodies (nAb) to AAV2. There was no change in sFLT-1 levels in
      bodily fluids. In the rAAV.sFLT-1 group, Best Corrected Visual Acuity (BCVA)
      improved by a median of 1.0 (IQR: -3.0 to 9.0) Early Treatment Diabetic
      Retinopathy Study (ETDRS) letters from baseline compared to a median of -5.0
      (IQR: -17.5 to 1.0) ETDRS letters change in the control group. Twelve (57%)
      patients in the rAAV.sFLT-1 group maintained or improved vision compared to 4
      (36%) in the control group. The median number of ranibizumab retreatments was 2.0
      (IQR: 1.0 to 6.0) for the gene therapy group compared to 4.0 (IQR: 3.5 to 4.0)
      for the control group. Interpretation rAAV.sFLT-1 combined with the option for co
      treatment appears to be a safe and promising approach to the treatment of wAMD.
      FUNDING: National Health and Medical Research Council of Australia (AP1010405),
      Lions Eye Institute, Perth Australia, Avalanche Biotechnologies, Menlo Pk, CA,
      USA.

PMID- 27865767
TI  - Neural stem cells promote nerve regeneration through IL12-induced Schwann cell
      differentiation.
AB  - Regeneration of injured peripheral nerves is a slow, complicated process that
      could be improved by implantation of neural stem cells (NSCs) or nerve conduit.
      Implantation of NSCs along with conduits promotes the regeneration of damaged
      nerve, likely because (i) conduit supports and guides axonal growth from one
      nerve stump to the other, while preventing fibrous tissue ingrowth and retaining
      neurotrophic factors; and (ii) implanted NSCs differentiate into Schwann cells
      and maintain a growth factor enriched microenvironment, which promotes nerve
      regeneration. In this study, we identified IL12p80 (homodimer of IL12p40) in the
      cell extracts of implanted nerve conduit combined with NSCs by using protein
      antibody array and Western blotting. Levels of IL12p80 in these conduits are 1.6
      fold higher than those in conduits without NSCs. In the sciatic nerve injury
      mouse model, implantation of NSCs combined with nerve conduit and IL12p80
      improves motor recovery and increases the diameter up to 4.5-fold, at the medial
      site of the regenerated nerve. In vitro study further revealed that IL12p80
      stimulates the Schwann cell differentiation of mouse NSCs through the
      phosphorylation of signal transducer and activator of transcription 3 (Stat3).
      These results suggest that IL12p80 can trigger Schwann cell differentiation of
      mouse NSCs through Stat3 phosphorylation and enhance the functional recovery and
      the diameter of regenerated nerves in a mouse sciatic nerve injury model.

PMID- 27865768
TI  - Regulation of extrasynaptic signaling by polysialylated NCAM: Impact for synaptic
      plasticity and cognitive functions.
AB  - The activation of synaptic N-methyl-d-aspartate-receptors (NMDARs) is crucial for
      induction of synaptic plasticity and supports cell survival, whereas activation
      of extrasynaptic NMDARs inhibits long-term potentiation and triggers
      neurodegeneration. A soluble polysialylated form of the neural cell adhesion
      molecule (polySia-NCAM) suppresses signaling through peri-/extrasynaptic GluN2B
      containing NMDARs. Genetic or enzymatic manipulations blocking this mechanism
      result in impaired synaptic plasticity and learning, which could be repaired by
      reintroduction of polySia, or inhibition of either GluN1/GluN2B receptors or
      downstream signaling through RasGRF1 and p38 MAP kinase. Ectodomain shedding of
      NCAM, and hence generation of soluble NCAM, is controlled by metalloproteases of
      a disintegrin and metalloprotease (ADAM) family. As polySia-NCAM is predominantly
      associated with GABAergic interneurons in the prefrontal cortex, it is noteworthy
      that EphrinA5/EphA3-induced ADAM10 activity promotes polySia-NCAM shedding in
      these neurons. Thus, in addition to the well-known regulation of synaptic NMDARs
      by the secreted molecule Reelin, shed polySia-NCAM may restrain activation of
      extrasynaptic NMDARs. These data support a concept that GABAergic interneuron
      derived extracellular proteins control the balance in synaptic/extrasynaptic
      NMDAR-mediated signaling in principal cells. Strikingly, dysregulation of Reelin
      or polySia expression is linked to schizophrenia. Thus, targeting of the
      GABAergic interneuron-principle cell communication and restoring the balance in
      synaptic/extrasynaptic NMDARs represent promising strategies for treatment of
      psychiatric diseases.

PMID- 27865769
TI  - Discrepancies in the diagnosis and classification of nonsteroidal anti
      inflammatory drug hypersensitivity reactions in children.
AB  - BACKGROUND: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) are
      frequently encountered in daily clinical practice. The aim of this study was to
      determine the confirmation rates, risk factors of NSAID hypersensitivity in
      children and to try to classify them with a standardized diagnostic protocol.
      METHODS: All patients with a suspicion of NSAID-induced hypersensitivity were
      evaluated with European Network for drug Allergy (ENDA) recommendations. The
      children were classified as selective responders (SRs) or cross-intolerant (CI)
      depending on the drug provocation test (DPT) results. RESULTS: We evaluated 106
      children with a suspicion of NSAID hypersensitivity. NSAID hypersensitivity was
      confirmed with tests in 31 patients; 4 (12.9%) were diagnosed by skin tests and
      27 (87.1%) by DPTs and two patients with a history of anaphylaxis by medical
      records. Eleven patients (33.3%) were classified as SRs, whereas twenty-two
      (66.6%) children as CIs. SRs and CIs were further classified as NSAID-induced
      urticaria/angioedema (n = 8), NSAID-exacerbated cutaneous disease (n = 6) and
      NSAID-exacerbated respiratory disease (n = 1) and single NSAID-induced
      urticaria/angioedema and/or anaphylaxis (n = 11). Eight (24.2%) patients could
      not be categorized according to ENDA/GA2LEN classification; one CI patient could
      not be classified based on pathomechanisms, seven CIs could not be categorized
      based on the underlying disease and clinical manifestations. A reaction within an
      hour of drug intake (aOR:3.0, 95% confidence interval: 1.18-7.67, p = 0.021), a
      history with multiple NSAIDs hypersensitivity (aOR:2.9, 95% confidence interval:
      1.16-7.60, p = 0.022), and family history of atopy (aOR:4.0, 95% confidence
      interval: 1.50-10.82, p = 0.006) were found as the independent risk factors
      related to confirmed NSAID hypersensitivity. CONCLUSIONS: This study suggests the
      presence of different phenotypes which do not fit into the current
      classifications in children with NSAID hypersensitivity.

PMID- 27865770
TI  - Effect of lipid environment on amyloid fibril formation of human serum amyloid A.
AB  - Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis and a
      component of high-density lipoproteins (HDLs), thus it is essential to
      investigate the amyloid fibril formation of SAA under a lipid environment. We
      used synthetic fragment peptides corresponding to the N-terminal (residues 1-27)
      and central (residues 43-63) regions of the SAA molecule, which are known to have
      amyloidogenic properties. Measurements of tryptophan fluorescence in conjunction
      with circular dichroism showed that SAA (1-27) peptide binds to neutral and
      acidic lysophospholipids, whereas SAA (43-63) peptide binds only to acidic
      lysophospholipids. For both these SAA peptides, binding to lysophospholipids
      inhibited heparin-induced amyloid-like fibril formation by stabilizing the alpha
      helical structure. However, acidic lysophospholipids implied a possibility to
      promote fibril formation of SAA (1-27) peptide by themselves. These results
      suggest that the amyloid fibril formation of SAA may be modulated by altering the
      lipid head group composition of HDLs during metabolism.

PMID- 27865771
TI  - Cholinergic activation affects the acute and chronic antinociceptive effects of
      morphine.
AB  - Current studies indicate that the cholinergic and opioid systems interact to
      modulate pain. In the present work, we investigated the influence of the
      cholinesterase inhibitors, donepezil (0.5; 1 or 3mg/kg, i.p.) and rivastigmine
      (0.03; 0.5 or 1mg/kg, i.p.), on the acute antinociceptive effects of morphine
      (5mg/kg, i.p.) in the hot plate test in mice. Herein, both inhibitors were found
      to enhance and prolong the analgesic effects of morphine without affecting
      latencies themselves. In an extension of this work, we determined which
      cholinergic receptors subtype mediates the enhancement of analgesic effects of
      morphine, following inhibition of cholinesterases. In this part of the study,
      scopolamine (0.5mg/kg, i.p.), a muscarinic cholinergic receptors antagonist, but
      not mecamylamine (3mg/kg, i.p.), a nicotinic cholinergic receptors antagonist,
      reversed the enhancing effects of donepezil (3mg/kg, i.p.) and rivastigmine
      (1mg/kg, i.p.) on the morphine antinociception. Moreover, both cholinesterase
      inhibitors attenuated the development of tolerance to the antinociceptive effects
      of morphine. In contrast, acute administration of donepezil (3mg/kg, i.p.) or
      rivastigmine (1mg/kg, i.p.) on the day of expression of tolerance, had no effect
      on the already developed morphine tolerance. What is more, in both set of
      experiments, rivastigmine was slightly more potent than donepezil due to the
      broader inhibitory spectrum of this drug on acetylcholine degradation. Thus, our
      results suggest that the cholinesterase inhibitors, donepezil and rivastigmine,
      may be administered with morphine in order to enhance the latter's analgesic
      effects for the treatment of acute and chronic pain.

PMID- 27865772
TI  - Kissing bugs can generalize and discriminate between different bitter compounds.
AB  - Animals make use of contact chemoreception structures to examine the quality of
      potential food sources. During this evaluation they can detect nutritious
      compounds that promote feeding and recognize toxins that trigger evasive
      behaviors. Although animals can easily distinguish between stimuli of different
      gustatory qualities (bitter, salty, sweet, etc.), their ability to discriminate
      between compounds of the same quality may be limited. Numerous plants produce
      alkaloids, compounds that elicit aversive behaviors in phytophagous insects and
      almost uniformly evoke a bitter taste for man. In hematophagous insects, however,
      the effect of feeding deterrent molecules has been barely studied. Recent studies
      showed that feeding in Rhodnius prolixus can be negatively modulated by the
      presence of alkaloids such as quinine (QUI) and caffeine (CAF), compounds that
      elicit similar aversive responses. Here, we applied associative and non
      associative learning paradigms to examine under two behavioral contexts the
      ability of R. prolixus to distinguish, discriminate and/or generalize between
      these two bitter compounds, QUI and CAF. Our results show that bugs innately
      repelled by bitter compounds can change their behavior from avoidance to
      indifference or even to preference according to their previous experiences. After
      an aversive operant conditioning with QUI or CAF, R. prolixus modified its
      behavior in a direct but also in a cross-compound manner, suggesting the
      occurrence of a generalization process between these two alkaloids. Conversely,
      after a long pre-exposure to each alkaloid, bugs decreased their avoidance to the
      compound used during pre-exposure but still expressed an avoidance of the novel
      compound, proving that QUI and CAF are detected separately. Our results suggest
      that R. prolixus is able to discriminate between QUI and CAF, although after an
      associative conditioning they express a symmetrical cross-generalization. This
      kind of studies adds insight into the gustatory sense of a blood-sucking model
      but also into the learning abilities of hematophagous insects.

PMID- 27865773
TI  - Particulate suspension effect on peristaltically induced unsteady pulsatile flow
      in a narrow artery: Blood flow model.
AB  - This work is concerned with theoretically investigating the pulsatile flow of a
      fluid with suspended particles in a flow driven by peristaltic waves that deform
      the wall of a small blood artery in the shape of traveling sinusoidal waves with
      constant velocity. The problem formulation in the wave frame of reference is
      presented and the governing equations are developed up to the second-order in
      terms of the asymptotic expansion of Womersley number which characterizes the
      unsteady effect in the wave frame. We suppose that the flow rate imposed, in this
      frame, is a function versus time. The analytical solution of the problem is
      achieved using the long wavelength approximation where Reynolds number is
      considered small with reference to the blood flow in the circulatory system. The
      present study inspects novelties brought about into the classic peristaltic
      mechanism by the inclusion of Womersley number, and the critical values of
      concentration and occlusion on the flow characteristics in a small artery with
      flexible walls. Momentum and mass equations for the fluid and particle phases are
      solved by means of a perturbation analysis in which the occlusion is a small
      parameter. Closed form solutions are obtained for the fluid/particle velocity
      distributions, stream function, pressure rise, friction force, wall shear stress,
      instantaneous mechanical efficiency, and time-averaged mechanical efficiency. The
      physical explanation of the Segre-Silberberg effect is introduced and the
      trapping phenomenon of plasma for haemodilution and haemoconcentration cases is
      discussed. It has been deduced that the width of the closed plasma streamlines is
      increased while their number is minimally reduced in case of haemoconcentration.
      This mathematical problem has numerous applications in various branches in
      science including blood flow in small blood vessels. Several results of other
      models can be deduced as limiting cases of our situation.

PMID- 27865774
TI  - A systems toxicology approach for comparative assessment: Biological impact of an
      aerosol from a candidate modified-risk tobacco product and cigarette smoke on
      human organotypic bronchial epithelial cultures.
AB  - This study reports a comparative assessment of the biological impact of a heated
      tobacco aerosol from the tobacco heating system (THS) 2.2 and smoke from a
      combustible 3R4F cigarette. Human organotypic bronchial epithelial cultures were
      exposed to an aerosol from THS2.2 (a candidate modified-risk tobacco product) or
      3R4F smoke at similar nicotine concentrations. A systems toxicology approach was
      applied to enable a comprehensive exposure impact assessment. Culture histology,
      cytotoxicity, secreted pro-inflammatory mediators, ciliary beating, and genome
      wide mRNA/miRNA profiles were assessed at various time points post-exposure.
      Series of experimental repetitions were conducted to increase the robustness of
      the assessment. At similar nicotine concentrations, THS2.2 aerosol elicited lower
      cytotoxicity compared with 3R4F smoke. No morphological change was observed
      following exposure to THS2.2 aerosol, even at nicotine concentration three times
      that of 3R4F smoke. Lower levels of secreted mediators and fewer miRNA
      alterations were observed following exposure to THS2.2 aerosol than following
      3R4F smoke. Based on the computational analysis of the gene expression changes,
      3R4F (0.13 mg nicotine/L) elicited the highest biological impact (100%) in the
      context of Cell Fate, Cell Proliferation, Cell Stress, and Inflammatory Network
      Models at 4 h post-exposure. Whereas, the corresponding impact of THS2.2 (0.14 mg
      nicotine/L) was 7.6%.

PMID- 27865775
TI  - Epidemiology and outcomes from out-of-hospital cardiac arrests in England.
AB  - INTRODUCTION: This study reports the epidemiology and outcomes from out-of
      hospital cardiac arrest (OHCA) in England during 2014. METHODS: Prospective
      observational study from the national OHCA registry. The incidence, demographic
      and outcomes of patients who were treated for an OHCA between 1st January 2014
      and 31st December 2014 in 10 English ambulance service (EMS) regions, serving a
      population of almost 54 million, are reported in accordance with Utstein
      recommendations. RESULTS: 28,729 OHCA cases of EMS treated cardiac arrests were
      reported (53 per 100,000 of resident population). The mean age was 68.6 (SD=19.6)
      years and 41.3% were female. Most (83%) occurred in a place of residence, 52.7%
      were witnessed by either the EMS or a bystander. In non-EMS witnessed cases,
      55.2% received bystander CPR whilst public access defibrillation was used rarely
      (2.3%). Cardiac aetiology was the leading cause of cardiac arrest (60.9%). The
      initial rhythm was asystole in 42.4% of all cases and was shockable (VF or pVT)
      in 20.6%. Return of spontaneous circulation at hospital transfer was evident in
      25.8% (n=6302) and survival to hospital discharge was 7.9%. CONCLUSION: Cardiac
      arrest is an important cause of death in England. With less than one in ten
      patients surviving, there is scope to improve outcomes. Survival rates were
      highest amongst those who received bystander CPR and public access
      defibrillation.

PMID- 27865776
TI  - Post-cardiac arrest shock treated with veno-arterial extracorporeal membrane
      oxygenation: An observational study and propensity-score analysis.
AB  - PURPOSE: Cardiogenic shock due to post-resuscitation myocardial dysfunction is a
      major cause of mortality among patients hospitalized after cardiac arrest (CA).
      Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been proposed in
      the most severe cases but the level of evidence is very low. We assessed
      characteristics, outcome and prognostic factors of patients treated with VA-ECMO
      for post-CA shock. METHODS: Using a large regional registry, we focused on all CA
      admitted in ICU. Among those who developed a post-CA shock, prognostic was
      compared according to VA-ECMO use, using logistic regression and propensity
      score. Specific prognostic factors were identified among VA-ECMO patients.
      RESULTS: Among 2988 patients admitted after CA, 1489 developed a post-CA shock,
      and were included. They were mostly male (68%), with mean age 63 years (SD=15).
      Fiflty-two patients (3.5%) were treated with VA-ECMO, mostly patients with
      ischemic cause of CA (67%). Among patients with post-CA shock, 312 (21%) were
      discharged alive (25% in VA-ECMO group, 21% in control group, P=0.45). After
      adjustment for pre-hospital and in-hospital factors, survival did not differ
      among patients treated with VA-ECMO (OR for survival=0.9, 95%CI 0.4-2.3, P=0.84).
      After propensity-score matching, results were consistent. Among patients treated
      with VA-ECMO, initial arterial pH (OR=1.7 per 0.1 increase, 95%CI 1.0-2.8,
      P=0.04) and implantation of VA-ECMO over 24h after ROSC (OR=20.0, 95%CI 1.4
      277.3, P=0.03) were associated with survival. CONCLUSIONS: Post-CA shock is
      frequent and is associated with a high mortality rate. When used in selected
      patients, we observed that VA-ECMO could be an appropriate treatment.

PMID- 27865777
TI  - Making health systems research work: time to shift funding to locally-led
      research in the South.

PMID- 27865778
TI  - Curcumin inhibits glial scar formation by suppressing astrocyte-induced
      inflammation and fibrosis in vitro and in vivo.
AB  - Spinal cord injury (SCI) leads to glial scar formation by astrocytes, which
      severely hinders neural regeneration. Curcumin (cur) can inhibit glial scar
      formation, but the underlying mechanism is not fully understood. Using both in
      vivo and in vitro experiments, the current study investigated the phenotypic
      transformation of astrocytes following cur and siRNA intervention during the
      processes of inflammation and fibrosis and determined details of the relationship
      between cur treatment and the glial scar components GFAP and CSPG. We found that
      cur and NF-kappab p65 siRNA could inhibit astrocyte activation through
      suppressing NF-kappab signaling pathway, which led to down-regulate the
      expression of chemokines MCP-1, RANTES and CXCL10 released by astrocytes and
      decreased macrophage and T-cell infiltration, thus reducing the inflammation in
      the glial scar. In addition, silencing SOX-9 may reduce the deposition of
      extracellular matrix CSPG; whereas its over-expression could increase the CSPG
      expression. Cur suppressedSOX-9-inducedCSPG deposition, reduced alpha-SMA (an
      important symbol of fibrosis) expression in astrocytes, altered astrocyte
      phenotype, and inhibited glial scar formation by regulating fibrosis. This study
      confirmed that cur could regulate both the NF-kappab and SOX9 signaling pathways
      and reduce the expression of intracellular and extracellular glial scar
      components through dual-target regulating both inflammation and fibrosis after
      SCI in the rat. This study provides an important hypothesis centered on the dual
      inhibition of intracellular and extracellular glial scar components as a
      treatment strategy for SCI.

PMID- 27865781
TI  - Imaging Transcriptional Regulation of Eukaryotic mRNA Genes: Advances and
      Outlook.
AB  - Regulation of eukaryotic transcription in vivo occurs at distinct stages.
      Previous research has identified many active or repressive transcription factors
      (TFs) and core transcription components and studied their functions in vitro and
      in vivo. Nonetheless, how individual TFs act in concert to regulate mRNA gene
      expression in a single cell remains poorly understood. Direct observation of TF
      assembly and disassembly and various biochemical reactions during transcription
      of a single-copy gene in vivo is the ideal approach to study this problem.
      Research in this area requires developing novel techniques for single-cell
      transcription imaging and integrating imaging studies into understanding the
      molecular biology of transcription. In the past decade, advanced cell imaging has
      enabled unprecedented capabilities to visualize individual TF molecules, to track
      single transcription sites, and to detect individual mRNA in fixed and living
      cells. These studies have raised several novel insights on transcriptional
      regulation such as the "hit-and-run" model and transcription bursting that could
      not be obtained by in vitro biochemistry analysis. At this point, the key
      question is how to achieve deeper understandings or discover novel mechanisms of
      eukaryotic transcriptional regulation by imaging transcription in single cells.
      Meanwhile, further technical advancements are likely required for visualizing
      distinct kinetic steps of transcription on a single-copy gene in vivo. This
      review article summarizes recent progress in the field and describes the
      challenges and opportunities ahead.

PMID- 27865782
TI  - Application of nano-LC-MALDI-TOF/TOF-MS for proteomic analysis of microvesicles.
AB  - Activated platelets and platelet derived microvesicles (PMVs) emerged recently to
      be promising biomarkers. There is no universal procedure to carry out the
      proteomic analysis on microvesicles. In this study we proposed a nano-liquid
      chromatography (nano-LC) technique coupled off-line with a spectrometric
      measurement MALDI-TOF-MS/MS as a throughput and time-saving procedure. In this
      study we developed a simplified method to evaluate the protein composition of
      platelet organelles and PMVs. Platelet-rich plasma (PRP) was collected from
      healthy donors. PMVs were generated from washed and thrombin activated platelets.
      Activated platelets from every donor were used to compare the PMV proteome.
      Enzymatic digestion of protein lysate was carried out using Filter Aided Sample
      Preparation (FASP) method with trypsin as a proteolytic enzyme. Tryptic peptides
      derived from PMVs and activated platelets were analysed using nano-LC coupled off
      line mode with a MALDI-TOF/TOF-MS. PMV and platelet protein identification was
      performed using the Mascot engine for searching against the Swiss-Prot human
      database. The precision tolerance was 100ppm for peptide masses and 0.7Da for
      fragment ion masses. Individual peptide matches with a score above 28 were
      considered statistically significant. In total, 446 proteins were identified in
      PMVs and 513 proteins in activated platelets. Among them 190 were specific for
      activated platelets and 123 were PMV specific. Cellular component analysis of
      identified proteins revealed that PMVs contained relatively more extracellular
      proteins than activated platelets (9.6 vs. 6.0 %) and unique synaptic proteins
      (0.3%). A new simplified bottom-up method for PMV proteome analysis allowed
      eliminating the drawbacks of the previously used protocols. This approach can be
      used in PMV proteome identification.

PMID- 27865783
TI  - The modulation of inflammatory parameters, Brain-derived neurotrophic factor
      levels and global histone H4 acetylation status in peripheral blood of patients
      with Gaucher disease type 1.
AB  - OBJECTIVES: Gaucher's disease type 1 (GD1) pathophysiology includes an imbalance
      on brain-derived neurotrophic factor (BDNF) levels and in the inflammatory
      system. However, the pathways involved remain poorly understood. The hypothesis
      of this study is that epigenetic mechanisms might be involved, at least
      partially, in this phenomenon. DESIGN AND METHODS: This study investigated the
      BDNF modulation, global histone H4 acetylation and pro- and anti-inflammatory
      cytokines levels in the peripheral blood of GD1 patients (n=10) when compared
      with control samples (CS) (n=11). RESULTS: The results showed a significant
      increase in Chitotriosidase (CT) (p=0.019) and decreased beta-glucosidase (GBA)
      activities (p=0.001) in GD1 samples when compared to CS, for GD1 diagnostic
      confirmation. Reduced levels of BDNF (p=0.004) and elevated levels of TNF-alpha
      (p=0.017) and IL-4 (p=0.035) were also found in the GD group. No significant
      differences were observed in IL-6 or IL-17a levels between groups (p>0.05).
      Finally, a trend on higher global histone H4 acetylation levels (p=0.054) was
      observed in the control group when compared to GD1 individuals. CONCLUSIONS:
      Combined, these results suggest inflammatory cytokines imbalance, reduced BDNF
      levels and global histone H4 hypoacetylation status in GD type 1 physiopathology.
      These preliminary findings may open new avenues to introduce therapies and
      strategies in the preventive management and treatment of this population.

PMID- 27865780
TI  - RasIns: Genetically Encoded Intrabodies of Activated Ras Proteins.
AB  - K- and H-Ras are the most commonly mutated genes in human tumors and are critical
      for conferring and maintaining the oncogenic phenotype in tumors with poor
      prognoses. Here, we design genetically encoded antibody-like ligands
      (intrabodies) that recognize active, GTP-bound K- and H-Ras. These ligands, which
      use the 10th domain of human fibronectin as their scaffold, are stable inside the
      cells and when fused with a fluorescent protein label, the constitutively active
      G12V mutant H-Ras. Primary selection of ligands against Ras with mRNA display
      resulted in an intrabody (termed RasIn1) that binds with a KD of 2.1MUM to H
      Ras(G12V) (GTP), excellent state selectivity, and remarkable specificity for K-
      and H-Ras. RasIn1 recognizes residues in the Switch I region of Ras, similar to
      Raf-RBD, and competes with Raf-RBD for binding. An affinity maturation selection
      based on RasIn1 resulted in RasIn2, which binds with a KD of 120nM and also
      retains excellent state selectivity. Both of these intrabodies colocalize with H
      Ras, K-Ras, and G12V mutants inside the cells, providing new potential tools to
      monitor and modulate Ras-mediated signaling. Finally, RasIn1 and Rasin2 both
      display selectivity for the G12V mutants as compared with wild-type Ras providing
      a potential route for mutant selective recognition of Ras.

PMID- 27865779
TI  - Impairment of neurovascular coupling in Type 1 Diabetes Mellitus in rats is
      prevented by pancreatic islet transplantation and reversed by a semi-selective
      PKC inhibitor.
AB  - Streptozotocin (STZ)-induced chronic hyperglycemia has a detrimental effect on
      neurovascular coupling, linked to increased PKC-mediated phosphorylation and PKC
      isoform expression changes. Here, we sought to determine whether: 1) selective
      PKC-alpha/beta/gamma inhibitor, GF109203X, could reverse the effects of chronic
      hyperglycemia on cerebrovascular reactivity; 2) pancreatic islet transplantation
      could prevent the development of cerebrovascular impairment seen in a rat model
      of Type 1 Diabetes. We studied the effect of GF109203X in diabetic (DM), non
      diabetic (ND), and transplanted (TR) Lewis rats during either sciatic nerve
      stimulation (SNS) or the topical applications of the large-conductance Ca2+
      operated K+(BKCa) channel opener, NS1619, or the K+ inward rectifier (Kir)
      channel agonist, KCl. Pial arteriole diameter changes were monitored using a
      closed cranial window in vivo microscopy technique. The pial arteriole dilatory
      response associated with SNS was decreased by ~45%, when comparing DM vs either
      ND or TR rats. Also, pial arteriolar dilations to topical KCl and NS1619 were
      largely attenuated in DM rats, but not in ND or TR animals. These responses were
      completely restored by the acute application of GF109203X to the brain surface.
      The PKC inhibitor had no effect on vascular responses in normoglycemic and TR
      animals. In conclusion, DM-associated chronic impairment of neurovascular
      coupling may be readily reversed by a PKC-alpha/beta/gamma inhibitor or prevented
      via pancreatic islet transplantation. We believe that specific PCK isoforms
      (alpha/beta/gamma) are mechanistically linked to the neurovascular uncoupling
      seen with hyperglycemia.

PMID- 27865784
TI  - A Comparison of Cell-Free DNA Isolation Kits: Isolation and Quantification of
      Cell-Free DNA in Plasma.
AB  - The analysis of cell-free DNA (cfDNA) as a sensitive biomarker for cancer
      diagnosis and monitoring has resulted in a need for efficient and standardized
      cfDNA isolation. In this study, we compared the isolation efficiency of the
      QIAamp circulating nucleic acid kit (QIA) with four other cfDNA isolation kits:
      the PME free-circulating DNA Extraction Kit (PME), the Maxwell RSC ccfDNA Plasma
      Kit (RSC), the EpiQuick Circulating Cell-Free DNA Isolation Kit (EQ), and two
      consecutive versions of the NEXTprep-Mag cfDNA Isolation Kit (NpMV1/2). cfDNA was
      isolated from 10 plasma samples, of which five contained KRAS mutated cell-free
      tumor DNA (ctDNA). Digital droplet PCR was used to quantify the total cfDNA
      concentration as well as the KRAS mutated ctDNA fraction. cfDNA integrity was
      assessed with real-time quantitative PCR. The QIA and the RSC kits displayed
      similar isolation efficiencies of both KRAS mutated ctDNA and nonmutated cfDNA,
      whereas the yield generated by the PME and NpMV2 kits was significantly lower.
      Real-time quantitative PCR indicated the presence of digital droplet PCR
      inhibiting agents in the eluates of the NpMV1 and EQ kits. To conclude, this
      study presents two highly efficient isolation kits for cfDNA isolation, of which
      the RSC kit has the advantage of a fully automated protocol over the labor
      intensive QIA kit.

PMID- 27865785
TI  - Dnmt1, Dnmt3a and Dnmt3b cooperate in photoreceptor and outer plexiform layer
      development in the mammalian retina.
AB  - Characterizing the role of epigenetic regulation in the mammalian retina is
      critical for understanding fundamental mechanisms of retinal development and
      disease. DNA methylation, an epigenetic modifier of genomic DNA, plays an
      important role in modulating networks of tissue and cell-specific gene
      expression. However, the impact of DNA methylation on retinal development and
      homeostasis of retinal neurons remains unclear. Here, we have created a tissue
      specific DNA methyltransferase (Dnmt) triple mutant mouse in an effort to
      characterize the impact of DNA methylation on retinal development and
      homeostasis. An Rx-Cre transgene was used to drive targeted mutation of all three
      murine Dnmt genes in the mouse retina encoding major DNA methylation enzymes
      DNMT1, DNMT3A and DNMT3B. The triple mutant mice represent a hypomorph model
      since Dnmt1 catalytic activity was still present and excision of Dnmt3a and
      Dnmt3b had only about 90% efficiency. Mutation of all three Dnmts resulted in
      global genomic hypomethylation and dramatic reorganization of the photoreceptor
      and synaptic layers within retina. Transcriptome and proteomic analyses
      demonstrated enrichment of dysregulated phototransduction and synaptic genes. The
      5 mC signal in triple mutant retina was confined to the central heterochromatin
      but reduced in the peripheral heterochromatin region of photoreceptor nuclei. In
      addition, we found a reduction of the 5 mC signal in ganglion cell nuclei.
      Collectively, this data suggests cooperation of all three Dnmts in the formation
      and homeostasis of photoreceptors and other retinal neurons within the mammalian
      retina, and highlight the relevance of epigenetic regulation to sensory retinal
      disorders and vision loss.

PMID- 27865786
TI  - Human Connectomics across the Life Span.
AB  - Connectomics has enhanced our understanding of neurocognitive development and
      decline by the integration of network sciences into studies across different
      stages of the human life span. However, these studies commonly occurred
      independently, missing the opportunity to test integrated models of the dynamical
      brain organization across the entire life span. In this review article, we survey
      empirical findings in life-span connectomics and propose a generative framework
      for computationally modeling the connectome over the human life span. This
      framework highlights initial findings that across the life span, the human
      connectome gradually shifts from an 'anatomically driven' organization to one
      that is more 'topological'. Finally, we consider recent advances that are
      promising to provide an integrative and systems perspective of human brain
      plasticity as well as underscore the pitfalls and challenges.

PMID- 27865787
TI  - The Emerging Social Neuroscience of Justice Motivation.
AB  - Humans from a very early age are deeply sensitive to issues of justice and
      fairness, both in their own lives and in the lives of others. Most people are
      highly motivated to pursue justice and condemn injustice. Where does this concern
      for justice come from? Here we integrate findings in evolution, development,
      psychology, behavioral economics, and social neuroscience to highlight multiple
      potential drivers of justice motivation. We argue that justice motivation arises
      from complementary rapid heuristics and deliberation, each utilizing distinct and
      interacting neural circuitry. This framework is useful for explaining observed
      symmetries and asymmetries in responses to experiencing or observing injustice
      and may help to explain why individuals vary in their responses to injustice.

PMID- 27865790
TI  - Maxillomandibular Advancement Surgery for Patients Who Are Refractory to
      Continuous Positive Airway Pressure: Are There Predictors of Success?
AB  - PURPOSE: This pilot study was conducted to determine the effectiveness of
      maxillomandibular advancement (MMA) in the treatment of patients with moderate to
      severe obstructive sleep apnea (OSA). The predictive value of clinical,
      radiographic, and treatment-related variables also was investigated in relation
      to the success or failure of MMA as treatment for OSA. MATERIALS AND METHODS: A
      retrospective study design was used to assess the outcomes of MMA in patients
      with moderate to severe OSA (apnea hypopnea index [AHI] >15 events per hour) at
      the University of Michigan (Ann Arbor, MI). Data collected included clinical,
      radiographic, and polysomnographic findings. Primary outcomes of interest
      included the AHI, minimal oxygen saturation, and percentage of time spent with
      oxygen saturation lower than 88% as measured by polysomnography. RESULTS: Twenty
      patients met the inclusion criteria for the study (mean age, 48.8 +/- 12.3 yr).
      Mean body mass index decreased from 32.03 +/- 5.13 kg/m2 at baseline to 29.75 +/-
      5.23 kg/m2 at follow-up (P = .001). Mean advancements were 13.5 +/- 2.7 mm at
      point B and 16.1 +/- 4.5 mm at the pogonion. A 4.5-fold increase in minimal cross
      sectional area and a 2.2-fold increase in airway volume were achieved on average.
      Patients showed a 68.5% decrease in mean AHI from 49.4 to 15.6 events per hour (P
      < .001). The percentage of time with oxygen saturation lower than 88% was
      significantly decreased from 15.4% at baseline to 1.4% after surgery (P = .014).
      The overall surgical success rate was 55% (11 of 20) based on an AHI of fewer
      than 15 events per hour. CONCLUSIONS: These preliminary results indicate that MMA
      surgery might be highly effective for select patients with moderate to severe
      OSA. Despite large increases in airway dimensions, a surgical success rate of 55%
      was achieved in the overall sample. Assessment of predictive variables for
      success and failure are discussed.

PMID- 27865788
TI  - Testosterone and immune-reproductive tradeoffs in healthy women.
AB  - Although testosterone (T) has been characterized as universally immunosuppressive
      across species and sexes, recent ecoimmunology research suggests that T's
      immunomodulatory effects (enhancing/suppressing) depend on the organism's
      reproductive context. Very little is known about the immune effects of T in
      healthy females, and even less about how reproductive effort modulates the immune
      effects of T in humans. We investigated how the interaction between endogenous T
      and sexual activity predicted menstrual cycle-related changes in several measures
      of immunity: inflammation (indexed by interleukin-6, IL-6), adaptive immunity
      (indexed by immunoglobulin A, IgA), and functional immunity (indexed by
      bactericidal assay). Thirty-two healthy women (sexually abstinent, N=17; sexually
      active with one male partner, N=15) provided saliva samples at four points in the
      menstrual cycle: menses, follicular, ovulation, and luteal phases. Among sexually
      abstinent women, T was positively associated with IL-6 across the cycle; for
      sexually active women, however, T was positively associated with IL-6 in the
      luteal phase only, and negatively associated with IL-6 at ovulation. High T
      predicted higher IgA among women who reported infrequent intercourse, but lower
      IgA among women who reported very frequent intercourse. Finally, across groups, T
      was positively associated with greater bacterial killing at menses, but
      negatively associated in the luteal phase. Overall, rather than being universally
      immunosuppressive, T appeared to signal immunomodulation relevant to reproduction
      (e.g., lowering inflammation at ovulation, potentially preventing immune
      interference with conception). Our findings support the hypothesis that the
      immunomodulatory effects of endogenous T in healthy females depend on sexual and
      reproductive context.

PMID- 27865789
TI  - Anoxia ameliorates the dexamethasone-induced neurobehavioral alterations in the
      neonatal male rat pups.
AB  - Glucocorticoids and hypoxia are two essential factors affecting the brain
      development during labor and delivery. In addition to the neurobehavioral
      alterations induced separately by these factors, glucocorticoids can attenuate
      the deleterious consequences of severe hypoxia-ischemia on the brain development,
      acting as a neuroprotective agent in combination with hypoxia. The role of
      hypoxia in the combined action with corticosteroids is less clear. Severe hypoxia
      ischemia results in the massive activation of caspase-3, masking any other
      effects of hypoxia on the neonatal brain exposed to glucocorticoids. As a result,
      the effects of mild hypoxia on the developing brain pretreated with
      glucocorticoids remain unclear. To analyze this problem, 2-day-old male rats were
      treated with dexamethasone (DEX) before the subsequent exposure to mild 10-min
      anoxia or normoxia. The treatment with only DEX resulted in the delay in the
      development of the negative geotaxis reaction and in the decrease in locomotor
      activity of the neonatal male pups. The mild anoxic event attenuated these DEX
      induced neurobehavioral alterations. The treatment with DEX, but not the mild
      anoxic exposure alone, resulted in the delayed upregulation of active caspase-3
      in the prefrontal cortex and in the brainstem of the male pups. This
      glucocorticoid-induced upregulation of active caspase-3 was prevented by the
      anoxic event. The present findings evidence that mild anoxia is capable of
      ameliorating the glucocorticoid-induced neurodevelopmental alterations in the
      neonatal rats if the artificial or the naturally occurring increase in the levels
      of glucocorticoids occurred just before the episode of hypoxia.

PMID- 27865791
TI  - Efficacy of 2 Representative Topical Agents to Prevent Keloid Recurrence After
      Surgical Excision.
AB  - PURPOSE: Keloids are difficult to remove successfully and there is no universally
      accepted treatment. After surgical excision of the keloid, there are various
      management methods for prevention of keloid recurrence, such as intralesional
      injection, radiation, and topical agents. A few studies have compared topical
      agents with other treatments. The aim of this study was to investigate effective
      topical agents for the prevention of recurrent keloid after surgical excision.
      MATERIALS AND METHODS: Eligible articles were sought using core databases,
      including Medline, Embase, and Cochrane databases, up to April 2016. The
      predictor variables were mitomycin C (MC) and imiquimod cream treatment after
      keloid excision. The outcome variable was keloid recurrence rate. RESULTS: The
      search strategy identified 120 publications. After screening, 9 articles were
      selected for review. Articles were divided into 2 groups: MC and imiquimod cream.
      The recurrence rate after surgical excision in the MC group was estimated to be
      16.5%, and that in the imiquimod cream group was estimated to be 24.7%.
      CONCLUSION: If intralesional injection or radiation is not available, then MC or
      imiquimod 5% cream could be an effective alternative in preventing keloid
      recurrence.

PMID- 27865792
TI  - A quantitative proteomic screen of the Campylobacter jejuni flagellar-dependent
      secretome.
AB  - : Campylobacter jejuni is the leading cause of bacterial gastroenteritis in the
      world. A number of factors are believed to contribute to the ability of C. jejuni
      to cause disease within the human host including the secretion of non-flagellar
      proteins via the flagellar type III secretion system (FT3SS). Here for the first
      time we have utilised quantitative proteomics using stable isotope labelling by
      amino acids in cell culture (SILAC), and label-free liquid chromatography-mass
      spectrometry (LC/MS), to compare supernatant samples from C. jejuni M1 wild type
      and flagella-deficient (flgG mutant) strains to identify putative novel proteins
      secreted via the FT3SS. Genes encoding proteins that were candidates for
      flagellar secretion, derived from the LC/MS and SILAC datasets, were deleted.
      Infection of human CACO-2 tissue culture cells using these mutants resulted in
      the identification of novel genes required for interactions with these cells.
      This work has shown for the first time that both CJM1_0791 and CJM1_0395 are
      dependent on the flagellum for their presence in supernatants from C. jejuni
      stains M1 and 81-176. BIOLOGICAL SIGNIFICANCE: This study provides the most
      complete description of the Campylobac er jejuni secretome to date. SILAC and
      label-free proteomics comparing mutants with or without flagella have resulted in
      the identification of two C. jejuni proteins that are dependent on flagella for
      their export from the bacterial cell.

PMID- 27865793
TI  - Multiplexed mass spectrometry monitoring of biomarker candidates for
      osteoarthritis.
AB  - : The methods currently available for the diagnosis and monitoring of
      osteoarthritis (OA) are very limited and lack sensitivity. Being the most
      prevalent rheumatic disease, one of the most disabling pathologies worldwide and
      currently untreatable, there is a considerable interest pointed in the
      verification of specific biological markers for improving its diagnosis and
      disease progression studies. Considering the remarkable development of targeted
      proteomics methodologies in the frame of the Human Proteome Project, the aim of
      this work was to develop and apply a MRM-based method for the multiplexed
      analysis of a panel of 6 biomarker candidates for OA encoded by the Chromosome
      16, and another 8 proteins identified in previous shotgun studies as related with
      this pathology, in specimens derived from the human joint and serum. The method,
      targeting 35 different peptides, was applied to samples from human articular
      chondrocytes, healthy and osteoarthritic cartilage, synovial fluid and serum.
      Subsequently, a verification analysis of the biomarker value of these proteins
      was performed by single point measurements on a set of 116 serum samples, leading
      to the identification of increased amounts of Haptoglobin and von Willebrand
      Factor in OA patients. Altogether, the present work provides a tool for the
      multiplexed monitoring of 14 biomarker candidates for OA, and verifies for the
      first time the increased amount of two of these circulating markers in patients
      diagnosed with this disease. SIGNIFICANCE: We have developed an MRM method for
      the identification and relative quantification of a panel of 14 protein biomarker
      candidates for osteoarthritis. This method has been applied to analyze human
      articular chondrocytes, articular cartilage, synovial fluid, and finally a
      collection of 116 serum samples from healthy controls and patients suffering
      different degrees of osteoarthritis, in order to verify the biomarker usefulness
      of the candidates. HPT and VWF were validated as increased in OA patients.

PMID- 27865794
TI  - Mutations of cancer-related genes in benign tumors: the example of hidradenoma
      papilliferum.

PMID- 27865795
TI  - Hepatic angiomyolipomas may overexpress TFE3, but have no relevant genetic
      alterations.
AB  - The fusion or amplification of TFE3 has been identified as one of the molecular
      events underlying tumorigenesis in perivascular epithelioid cell tumors
      (PEComas). TFE3 rearrangements in PEComas are related to the morphological
      features of the epithelioid appearance and weaker expression of
      immunohistochemical muscular markers. This study aimed to clarify whether these
      genetic alterations are involved in hepatic angiomyolipomas (AMLs), which are a
      member of the PEComa tumor family. We examined 28 liver specimens (15 biopsies
      and 13 surgical specimens) of hepatic AMLs obtained from 26 patients. Renal AMLs
      (n=20), extrahepatorenal PEComas (n=3), lymphangiomyomatosis (n=8), and
      hepatocellular carcinomas (n=40) were used as a control. A histologic comparison
      between hepatic and renal AMLs revealed that the epithelioid appearance was more
      common in hepatic tumors (38% versus 0%, P=.006). In immunohistochemistry, the
      expression of HMB45 and Melan-A appeared to be more widespread in hepatic AMLs
      than in renal AMLs, whereas smooth muscle actin and desmin were less broadly
      expressed in hepatic tumors (all P<.001). TFE3 also appeared to be overexpressed
      in 6 (21%) of 26 hepatic AMLs and 3 (100%) of 3 PEComas, but in none of the renal
      AMLs. In fluorescence in situ hybridization, although all PEComas harbored a TFE3
      rearrangement or amplification, no genetic alterations were found in any hepatic
      AMLs. In conclusion, although hepatic AMLs and TFE3-rearranged PEComas share
      pathological features such as the epithelioid appearance and immunoreactivity to
      TFE3, TFE3 alterations are less likely to be a major molecular event driving
      tumorigenesis in hepatic AMLs.

PMID- 27865796
TI  - Bletilla striata: Medicinal uses, phytochemistry and pharmacological activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata (Thunb.) Reichb. f.
      (Orchidaceae), also known as Hyacinth Orchid and Baiji (Simplified Chinese: ),
      not only has been widely used for the treatment of hematemesis, hemoptysis, and
      traumatic bleeding due to the efficacy of arresting bleeding with astringent
      action, but also has been applied topically to overcome ulcers, sores, swellings,
      and chapped skin due to the efficacy of dispersing swelling and promoting tissue
      regeneration. Additional medical applications include the treatment of
      tuberculosis, malignant ulcers, hemorrhoids, anthrax, eye diseases, and
      silicosis. AIM OF THIS REVIEW: This review aims to provide up-to-date information
      on the botanical characterization, medicinal uses, chemical constituents,
      pharmacological activities, and toxicity of B. striata. In addition, this paper
      also focuses on the possible exploitation of this plant for the treatment of
      different diseases, and uncovers opportunities for future research. MATERIALS AND
      METHODS: The relevant information on B. striata was gathered from worldwide
      accepted scientific databases via an electronic search (Google Scholar, Web of
      Science, ScienceDirect, ACS Publications, PubMed, Wiley Online Library,
      SciFinder, CNKI). Information was also obtained from The Plant List, Chinese
      pharmacopoeia, Chinese herbal classics books, PhD and MSc dissertations, etc.
      RESULTS: A comprehensive analysis of the literature obtained through the above
      mentioned sources confirmed that the ethnomedical usages of B. striata have been
      recorded in Mongolia, Korea, Japan, and China. Phytochemical investigations
      revealed that the major chemical constituents of B. striata are polysaccharides,
      bibenzyls, phenanthrenes, triterpenoids and its saponins, steroids and its
      saponins, which also have been proven to be the main bioactive substances capable
      of exhibiting numerous pharmacological activities including wound healing,
      antiulcer, hemostasis, cytotoxicity, antimicrobial, anti-inflammation, anti
      oxidation, immunomodulation, anti-fibrosis, antiaging, anti-allergy, and anti
      itch. CONCLUSIONS: Preliminary investigations on pharmacological properties of B.
      striata have shown that B. striata is an outstanding astringent hemostatic
      medicinal, B. striata polysaccharides (BSP) as the major bioactive components not
      only capable of promoting wound healing, but also show good performance as a kind
      of promising natural biomaterial. More importantly, BSP are also reported to be
      excellent embolic material. However, further investigations need to be carried
      out to fully clarify its efficacy of dispersing swelling and promoting tissue
      regeneration. Moreover, this plant also needs a lot more investigations to
      clarify the pathways of absorption, distribution, metabolism and excretion, and
      to evaluate its long-term in vivo chronic toxicity before proceeding to the
      development of pharmaceutical formulation.

PMID- 27865797
TI  - Radboud Centre for Mitochondrial Medicine Pediatric MRI score.
AB  - We developed the first user-friendly, semi-quantitative, and quick-to-perform
      Radboud Centre for Mitochondrial Medicine Pediatric MRI score (RCMM-PMRIS),
      focusing on the six most commonly described neuroimaging abnormalities in the
      literature. The RCMM-PMRIS was validated through individual review of 30 sets of
      brain MRI studies in 24 patients with genetically confirmed mitochondrial
      disorders by six raters. The application of RCMM-PMRIS can help to define the
      extent of the brain involvement and therefore to assess the radiological
      mitochondrial disease severity, to monitor disease progression and consequently
      to act as an outcome measure for treatment effects in patients with mitochondrial
      disease.

PMID- 27865800
TI  - Action observation and motor imagery for rehabilitation in Parkinson's disease: A
      systematic review and an integrative hypothesis.
AB  - This article discusses recent evidence supporting the use of action observation
      therapy and motor imagery practice for rehabilitation of Parkinson's disease. A
      main question that emerges from the review regards the different effectiveness of
      these approaches and the possibility of integrating them into a single method to
      enhance motor behaviour in subjects with Parkinson's disease. In particular, the
      reviewed studies suggest that action observation therapy can have a positive
      effect on motor facilitation of patients and that a long-term rehabilitation
      program based on action observation therapy or motor imagery practice can bring
      some benefit on their motor recovery. Moreover, the paper discusses how the
      research on the combined use of action observation and motor imagery for motor
      improvements in healthy subjects may encourage the combined use of action
      observation therapy and motor imagery practice for therapeutic aims in
      Parkinson's disease. To date, this hypothesis has never been experimented.

PMID- 27865798
TI  - Adoptive transfer of ex vivo expanded Vgamma9Vdelta2 T cells in combination with
      zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of
      osteolytic breast cancer.
AB  - Bone metastases occur in over 75% of patients with advanced breast cancer and are
      responsible for high levels of morbidity and mortality. In this study, ex vivo
      expanded cytotoxic Vgamma9Vdelta2 T cells isolated from human peripheral blood
      were tested for their anti-cancer efficacy in combination with zoledronic acid
      (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded
      Vgamma9Vdelta2 T cells were cytotoxic against a panel of human breast cancer cell
      lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by
      Vgamma9Vdelta2 T cells. Vgamma9Vdelta2 T cells adoptively transferred into
      NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and
      multiple infusions of Vgamma9Vdelta2 T cells reduced tumour growth in the bone.
      ZOL pre-treatment potentiated the anti-cancer efficacy of Vgamma9Vdelta2 T cells,
      with mice showing further reductions in tumour burden. Mice treated with the
      combination also had reduced tumour burden of secondary pulmonary metastases, and
      decreased bone degradation. Our data suggests that adoptive transfer of
      Vgamma9Vdelta2 T cell in combination with ZOL may prove an effective
      immunotherapeutic approach for the treatment of breast cancer bone metastases.

PMID- 27865799
TI  - Oleic acid-induced ANGPTL4 enhances head and neck squamous cell carcinoma anoikis
      resistance and metastasis via up-regulation of fibronectin.
AB  - Obese patients have higher levels of free fatty acids (FFAs) in their plasma and
      a higher risk of cancer than their non-obese counterparts. However, the
      mechanisms involved in the regulation of cancer metastasis by FFAs remain
      unclear. In this study, we found that oleic acid (OA) induced angiopoietin-like 4
      (ANGPTL4) protein expression and secretion and conferred anoikis resistance to
      head and neck squamous cell carcinomas (HNSCCs). The autocrine production of OA
      induced ANGPTL4 further promoted HNSCC migration and invasion. In addition, the
      expression of peroxisome proliferator-activated receptor (PPAR) was essential for
      the OA-induced ANGPTL4 expression and invasion. The levels of OA-induced
      epithelial-mesenchymal transition markers, such as vimentin, MMP-9, and
      fibronectin and its downstream effectors Rac1/Cdc42, were significantly reduced
      in ANGPTL4-depleted cells. Knocking down fibronectin inhibited the expression of
      MMP-9 and repressed OA- and recombinant ANGPTL4-induced HNSCC invasion. On the
      other hand, ANGPTL4 siRNA inhibited OA-induced MMP-9 expression, which was
      reversed in fibronectin-overexpressing cells. Furthermore, the depletion of
      ANGPTL4 impeded the OA-primed metastatic seeding of tumor cells in the lungs.
      These results demonstrate that OA enhances HNSCC metastasis through the
      ANGPTL4/fibronectin/Rac1/Cdc42 and ANGPTL4/fibronectin/MMP-9 signaling axes.

PMID- 27865802
TI  - Improving the Medical Curriculum in Predoctoral Dental Education: Recommendations
      From the American Association of Oral and Maxillofacial Surgeons Committee on
      Predoctoral Education and Training.
AB  - Dental procedures are often performed on patients who present with some level of
      medical fragility. In many dental schools, the exercise of taking a medical
      history is all too often a transcription of information to the dental chart, with
      little emphasis on the presurgical risk assessment and the development of a
      treatment plan appropriate to the medical status of the dental patient. Changes
      in dentistry, driven by an increasingly medically complex population of dental
      patients, combined with treatment advances rooted in the biomedical sciences
      necessitate the adaptation of our dental education to include a stronger
      background in systemic health. Many predoctoral educators in the American
      Association of Oral and Maxillofacial Surgeons (AAOMS) have expressed concern
      about the medical preparedness of our dental students; therefore, the AAOMS and
      its Committee on Predoctoral Education and Training have provided recommendations
      for improving the medical curriculum in predoctoral dental education, including a
      strengthening of training in clinical medicine and biomedical sciences, with
      specific recommendations for improved training of our dental students and dental
      faculty.

PMID- 27865801
TI  - Long-term cognitive, emotional and neurogenic alterations induced by alcohol and
      methamphetamine exposure in adolescent rats.
AB  - A high proportion of young methamphetamine (MA) users simultaneously consume
      alcohol. However, the potential neurological and behavioural alterations induced
      by such a drug combination have not been systematically examined. We studied in
      adolescent rats the long-term effects of alcohol, MA, and alcohol and MA combined
      on anxiety-like behaviour, memory, and neurogenesis in the adult hippocampus.
      Rats received saline, ethanol (ETOH, 1.5g/kg), MA (MA, 2mg/kg), or ethanol and MA
      combined (ETHOH-MA, 1.5g/kg ethanol plus 2mg/kg MA) via oral gavage, once daily
      for 5 consecutive days. Open field (OF), elevated plus maze (EPM) and radial arm
      maze (RAM) tests were conducted following a 15-day withdrawal period. The results
      showed alterations in exploratory behaviour in the OF in the MA and ETOH-MA
      groups, and anxiety-like effects in the EPM in all three drug treatment groups.
      All three drug groups exhibited reference memory deficits in the RAM, but only
      the combination treatment group displayed alterations in working memory. Both MA
      and ETOH-MA treatments increased the length of doublecortin (DCX)-void gaps in
      the dentate gyrus but only ETOH-MA treatment increased the number of such gaps.
      An increased number and length of DCX-void gaps correlated with decreased
      exploratory activity in the OF, and impaired working memory in the RAM was
      associated with an augmented number of gaps. These findings suggest that
      alterations in adult hippocampal neurogenesis are linked to the persistent
      cognitive and behavioural deficits produced by alcohol and MA exposure.

PMID- 27865804
TI  - Ghost Cell Tumors.
AB  - Ghost cell tumors are a family of lesions that range in presentation from cyst to
      solid neoplasm and in behavior from benign to locally aggressive or metastatic.
      All are characterized by the presence of ameloblastic epithelium, ghost cells,
      and calcifications. This report presents the cases of a 14-year-old girl with a
      calcifying cystic odontogenic tumor (CCOT) and a 65-year-old woman with a
      peripheral dentinogenic ghost cell tumor (DGCT) with dysplastic changes, a rare
      locally invasive tumor of odontogenic epithelium. The first patient presented
      with a 1-year history of slowly progressing pain and swelling at the left body of
      the mandible. Initial panoramic radiograph displayed a mixed radiolucent and
      radiopaque lesion. An incisional biopsy yielded a diagnosis of CCOT.
      Decompression of the mass was completed; after 3 months, it was enucleated and
      immediately grafted with bone harvested from the anterior iliac crest. The second
      patient presented with a 3-month history of slowly progressing pain and swelling
      at the left body of the mandible. Initial panoramic radiograph depicted a mixed
      radiolucent and radiopaque lesion with saucerization of the buccal mandibular
      cortex. An incisional biopsy examination suggested a diagnosis of DGCT because of
      the presence of ghost cells, dentinoid, and islands of ameloblastic epithelium.
      Excision of the mass with peripheral ostectomy was completed. At 6 and 12 months
      of follow-up, no evidence of recurrence was noted.

PMID- 27865803
TI  - Leukoplakia-A Diagnostic and Management Algorithm.
AB  - Oral white lesions are frequently encountered in daily practice. Most white
      lesions are benign (eg, reactive keratoses or keratoses from inflammatory
      conditions) and the diagnosis is usually evident from the clinical presentation
      and histopathology. Leukoplakia is a common condition characterized by an
      increased risk for malignant transformation. Histopathology of leukoplakia can
      disclose hyperkeratosis with dysplasia or carcinoma or hyperkeratosis or
      parakeratosis without dysplasia. Treatment depends on demographic, social,
      clinical, and histopathologic factors. This review focuses on the diagnosis and
      management of oral leukoplakia.

PMID- 27865805
TI  - Transcriptional activation by MLL fusion proteins in leukemogenesis.
AB  - Chromosomal translocations involving the mixed lineage leukemia (MLL) gene cause
      aggressive leukemia. Fusion proteins of MLL and a component of the AF4 family/ENL
      family/P-TEFb complex (AEP) are responsible for two-thirds of MLL-associated
      leukemia cases. MLL-AEP fusion proteins trigger aberrant self-renewal of
      hematopoietic progenitors by constitutively activating self-renewal-related
      genes. MLL-AEP fusion proteins activate transcription initiation by loading the
      TATA-binding protein (TBP) to the TATA element via selectivity factor 1. Although
      AEP retains transcription elongation and mediator recruiting activities, the rate
      limiting step activated by MLL-AEP fusion proteins appears to be the TBP-loading
      step. This is contrary to prevailing views, in which the recruitment of
      transcription elongation activities are emphasized. Here, I review recent
      advances towards elucidating the mechanisms underlying gene activation by MLL-AEP
      fusion proteins in leukemogenesis.

PMID- 27865807
TI  - Response to the letter to editor on innovative metabolic operations by El Kadre
      and Tinoco.

PMID- 27865808
TI  - Postprandial hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass: an
      update.
AB  - Roux-en-Y gastric bypass (RYGB) is an efficient treatment for morbid obesity and
      reduces obesity-related co-morbidities. With the growing number of patients
      undergoing gastric bypass, complications now demand further attention.
      Postprandial hyperinsulinemic hypoglycemia (PHH) after Roux-en-Y gastric bypass
      is a complex condition, characterized by increased glucose variability including
      both hyperglycemic and hypoglycemic values. PHH seems to be more prevalent than
      previously suggested and is highly dependent on the choice of diagnostic tool,
      which has not yet been standardized. Questionnaires, an oral glucose tolerance
      test, a mixed meal tolerance test, and continuous glucose monitoring have been
      used, each with their own advantages. The condition is further complicated by a
      large group of asymptomatic cases. Patients with symptoms of PHH after gastric
      bypass are characterized by exaggerated insulin and glucagon-like peptide-1
      responses compared to asymptomatic operated patients. The counter-regulatory
      mechanisms responsible for preventing hypoglycemia appear to be altered. The
      cause of these changes is not entirely understood, and it remains difficult to
      identify patients at risk of developing hypoglycemia. Known risk factors are
      female sex, longer time since surgery, and lack of prior diabetes. Management of
      the hypoglycemic episodes is difficult, and only dietary modifications consisting
      of frequent and less carbohydrate-rich meals seem to be efficient. Medical
      treatments and surgical procedures have been attempted in few studies and still
      warrant further examination.

PMID- 27865806
TI  - Ikaros: Exploiting and targeting the hematopoietic stem cell niche in B
      progenitor acute lymphoblastic leukemia.
AB  - Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS
      are a hallmark of high-risk B-progenitor acute lymphoblastic leukemia (ALL), such
      as BCR-ABL1-positive (Ph+) and Ph-like ALL, and are associated with poor outcome
      even in the era of contemporary chemotherapy incorporating tyrosine kinase
      inhibitors. Recent experimental mouse modeling of B-progenitor ALL has shown that
      IKZF1 alterations have multiple effects, including arresting differentiation,
      skewing lineage of leukemia from myeloid to lymphoid, and, in Ph+ leukemia,
      conferring resistance to tyrosine kinase inhibitor (TKI) therapy without
      abrogating ABL1 inhibition. These effects are in part mediated by acquisition of
      an aberrant hematopoietic stem cell-like program accompanied by induction of cell
      surface expression of stem cell and adhesion molecules that mediate extravascular
      invasion and residence in the niche and activation of integrin signaling
      pathways. These effects can be exploited therapeutically using several
      approaches. IKZF1 alterations also result in upregulation of RXRA that encodes
      part of the heterodimeric retinoic acid X receptor. Rexinoids, a synthetic class
      of retinoids that bind specifically to retinoid "X" receptors such as bexarotene
      potently reverse aberrant adhesion and niche mislocalization in vivo and induce
      differentiation and cell cycle arrest. Focal adhesion kinase inhibitors block the
      downstream integrin-mediated signaling, reverse adhesion, and niche
      mislocalization. Both agents act synergistically with TKIs to prolong survival of
      Ph+ ALL in mouse and human xenograft model, with long-term remission induced by
      focal adhesion kinase inhibitors. Therefore, these findings provide important new
      conceptual insights into the mechanisms by which IKZF1 alterations result in drug
      resistance and indicate that therapeutic strategies directed against the pathways
      deregulated by mutation, rather than attempting to restore IKZF1 expression
      directly, represent promising therapeutic approaches in this disease.

PMID- 27865809
TI  - Duodenal-jejunal bypass attenuates progressive failure of pancreatic islets in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Preservation of pancreatic beta cell function has been increasingly
      appealing in the treatment of type 2 diabetes. Evidence is still limited on how
      bariatric surgery affects pancreatic beta cell apoptosis. SETTING: University
      medical center. OBJECTIVE: The study aimed to investigate the effect of a major
      component of Roux-en-Y gastric bypass, duodenal-jejunal bypass, on protecting
      pancreatic beta cells from progressive loss. METHODS: Forty-five normal Sprague
      Dawley rats were randomly assigned into 3 groups: duodenal-jejunal bypass (DJB)
      group (n = 16) and sham (S) group (n = 17), based upon the procedure received,
      and a control (C) group (n = 12) without any procedure performed, to eliminate
      potential traumatic effects from surgery. Ten days after surgery, streptozotocin
      (STZ, 45 mg/kg weight) was injected intraperitoneally into each animal, including
      the control animals, to selectively induce pancreatic beta cell apoptosis.
      Weight, food intake, plasma glucose level, and the results of an oral glucose
      tolerance test were measured before surgery, pre-STZ injection, and up to 4 weeks
      after STZ injection. Plasma insulin and glucagon-like peptide-1 levels were also
      assayed during oral glucose tolerance test. At the end, pancreatic tissues were
      sliced and stained for beta cell analysis. RESULTS: There were no significant
      differences in weight among all groups at any time points measured, despite rats
      in the S and C groups consuming more food than those in the DJB group as measured
      on day 10 (P<.05) and day 20 (P<.01) after STZ injection. Animals undergoing DJB
      did not experience symptoms typical of uncompensated diabetes, including
      hyperphagia and progressive weight loss. After STZ injection, fasting plasma
      glucose levels in the DJB group were significantly lower than those in the C and
      S groups (P<.001). When challenged by glucose load, DJB rats also had a better
      glycemic excursion (P<.01) and incretin response compared with C and S rats
      (P<.05). In addition, pancreatic beta cell size and mass was better preserved in
      DJB rats (P< .001). CONCLUSION: DJB is able to protect pancreatic beta cells from
      apoptosis, which leads to better glycemic control and delayed onset of diabetes.
      These results imply the necessity of including a DJB component when designing
      bariatric procedure to achieve a better long-term outcome.

PMID- 27865810
TI  - Improvement of anthropometric and biochemical, but not of vitamin A, status in
      adolescents who undergo Roux-en-Y gastric bypass: a 1-year follow up study.
AB  - BACKGROUND: The aim of this study was to describe anthropometric, biochemical, co
      morbidity, and vitamin A nutritional status in severely obese adolescents before
      and 30, 180, and 365 days after Roux-en-Y gastric bypass (RYGB). SETTING: Federal
      University of Rio de Janeiro, Rio de Janeiro, Brazil. METHODS: Sixty-four
      adolescents (15-19 years old) with a body mass index>=40 kg/m2 were enrolled in a
      prospective follow-up study. Vitamin A status was evaluated before surgery (T0),
      and 30 (T30), 180 (T180), and 365 (T365) days after surgery, applying biochemical
      and functional indicators. Anthropometric measures, lipid profile, glycemia, and
      basal insulin also were assessed. No patients were lost during follow-up.
      RESULTS: Before surgery, 26.6% of the sample group experienced vitamin A
      deficiency (VAD). Serum retinol levels dropped significantly 30 days after
      surgery and then returned to basal levels. There was a significant increase in
      the prevalence of beta-carotene deficiency and night blindness throughout the
      postsurgery period. A significant reduction in blood glucose, insulin resistance,
      lipid profile, and anthropometric parameters was observed. CONCLUSION: The
      finding that oral daily supplementation with 5000 IU retinol acetate failed to
      reverse VAD and night blindness after RYGB is highly significant. We recommend
      assessment of VAD and night blindness in extremely obese adolescents before and
      after RYGB. We further recommend monitoring for an additional 180 days (for VAD)
      and 365 days (for night blindness) after surgery, with particular attention to
      daily supplementation needs.

PMID- 27865811
TI  - Laparoscopic stomach intestinal pylorus sparing surgery in a patient with morbid
      obesity and situs inversus: first video case report.

PMID- 27865812
TI  - Laparoscopic adjustable gastric banding versus laparoscopic adjustable gastric
      banding with gastric plication: midterm outcomes in terms of weight loss and
      short term complications.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is a safe procedure
      with variable outcomes and large standard deviations. LAGB with gastric plication
      (LAGBP) is a new restrictive procedure that combines the lap band with gastric
      plication. This procedure, with its mechanism being below the band anatomically,
      should augment the weaknesses of the lap band: slips and inadequate weight loss.
      OBJECTIVE: Compare the weight loss results and complication rates between the
      LAGB and LAGBP. SETTING: Private practice. METHODS: Data was analyzed data from
      120 patients retrospectively from 2 surgeons at a single private institution.
      Seventy-six patients underwent LAGB, and 44 other patients underwent LAGBP
      between February 2011 and July 2013. All 120 patients are beyond the 1-year
      postoperative mark and 110 patients are beyond the 2-year postoperative mark. A
      subset analysis was performed comparing data from both procedures to evaluate
      weight loss and complications. RESULTS: There were no significant differences
      between preoperative age, weight, and body mass index between the patients who
      underwent either procedure. We had 47.4% and 52.3% follow-up at 1 year for LAGB
      and LAGBP, respectively, with 91.5% and 92.3% follow-up at 2 year for LAGB and
      LAGBP, respectively. Complications were low with LAGBP; however, it was not
      statistically significant (P = .54). The LAGBP had a greater percent excess
      weight loss, percent total weight loss, and percent excess body mass index lost
      compared with the LAGB at 3, 6, 9, 12, and 24 months, and these differences were
      statistically significant. Mean percent excess weight loss for LAGB and LAGBP was
      28.3% and 34.5% (P<.05) at 1 year and 32.1% and 39.2% (P<.05) at 2 years,
      respectively. CONCLUSION: LAGBP is a safe, feasible, and reproducible bariatric
      procedure. The LAGBP performs significantly better than the LAGB for weight loss.
      The complication and revision rates were slightly higher with LAGB than LAGBP.
      However, it was not statistically significant.

PMID- 27865813
TI  - Editorial: Barium swallow for hiatal hernia detection is unnecessary prior to
      primary sleeve gastrectomy.

PMID- 27865814
TI  - Obesity and the role of bariatric surgery in the surgical management of
      osteoarthritis of the hip and knee: a review of the literature.
AB  - Obesity accelerates the development of osteoarthritis of the knee and hip by
      exerting deleterious effects on joints through both biomechanical and also
      systemic inflammatory changes. The objective of this review was to evaluate the
      impact of obesity on lower limb biomechanics and total joint arthroplasty
      outcomes, as well as weight changes after joint arthroplasty and the role of
      bariatric surgery among patients requiring joint arthroplasty. The currently
      published data indicate that weight loss increases swing time, stride length,
      gait speed, and lower extremity range of motion. Total joint arthroplasty
      improves pain and joint function, but does not induce significant weight loss in
      the majority of patients. Bariatric surgery improves gait biomechanics, and in
      the severely obese patient with osteoarthritis improves pain and joint function.
      The evidence for supporting bariatric surgery before total joint arthroplasty is
      limited to retrospective reports with conflicting results. Fundamental clinical
      questions remain regarding the optimal management of morbid obesity and lower
      extremity arthritis, which should be the focus of future collaborations across
      disciplines providing care to patients with both conditions.

PMID- 27865815
TI  - Surgical standardization to prevent gastric stenosis after laparoscopic sleeve
      gastrectomy: a case series.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is accepted as a stand-alone
      bariatric procedure. A specific and potentially severe complication of LSG is
      gastric stenosis (GS). OBJECTIVE: Reviewing the treatment and prevention of GS
      after LSG. SETTING: University hospital, Taiwan. MATERIALS AND METHODS: A
      retrospective analysis was conducted involving all of the LSG cases (n = 927) at
      our institution between February 2007 and December 2015. RESULTS: Eight patients
      (0.8%) with GS were identified in our unit and 1 patient was transferred from
      another institution with symptomatic GS. The median intervals from initial LSG to
      the presence of symptoms, endoscopic dilation, and surgical revision were 14+/-30
      days (range, 7-103 days), 21+/-35.6 days (range, 9-110 days), and 36+/-473.9 days
      (range, 11-1185 days), respectively. The majority of stenoses were located at the
      incisura angularis (8/9 [88.9%]). Among the 9 patients, only 1 responded
      satisfactorily to repetitive endoscopic dilation and the remaining 8 patients
      required revisional laparoscopic surgery, including conversion to Roux-en-Y
      gastric bypass (n = 6), stricturoplasty (n = 1), and Roux-en-Y gastric bypass
      after failed seromyotomy (n = 1). No patients experienced recurrent symptoms of
      GS after revisional surgery. In September 2013, we modified our surgical
      techniques for the subsequent 489 patients and GS did not occur after the change
      in surgical procedures. CONCLUSION: A combined treatment modality, endoscopic
      intervention with and without surgical revision is essential for managing GSs.
      Based on our own experience, we emphasize the clinical significance of surgical
      standardization to prevent the occurrence of GS.

PMID- 27865816
TI  - Paired Editorial: Perioperative Outcome of Laparoscopic Sleeve Gastrectomy for
      High-Risk Patients.

PMID- 27865817
TI  - Development and piloting the Woman Centred Care Scale (WCCS).
AB  - PROBLEM/BACKGROUND: In midwifery we espouse a woman centred care approach to
      practice, yet in midwifery education no valid instrument exists with which to
      measure the performance of these behaviours in midwifery students. AIM: To
      develop and validate an instrument to measure woman centred care behaviours in
      midwifery students. METHOD: We identified four core concepts; woman's sphere,
      holism, self-determination and the shared power relationship. We mapped 18
      individual descriptive care behaviours (from the Australian National Competency
      Standards for the Midwife) to these concepts to create an instrument to
      articulate and measure care behaviours that are specifically woman centred.
      Review by expert midwifery clinicians ensured face, content and construct
      validity of the scale and predictive validity and reliability were tested in a
      simulated learning environment. Midwifery students were video recorded performing
      a clinical skill and the videos were reviewed and rated by two expert clinicians
      who assessed the woman centred care behaviours demonstrated by the students
      (n=69). FINDINGS/DISCUSSION: Test and re-test reliability of the instrument was
      high for each of the individual raters (Kappa 0.946 and 0.849 respectively
      p<0.001). However, when raters were compared there were differences between their
      scores suggesting variation in their expectations of woman centred care
      behaviours (Kappa 0.470, p<0.001). Midwifery students who had repeated exposures
      to higher levels of simulation fidelity demonstrated higher levels of woman
      centred care behaviours. CONCLUSION: The WCCS has implications for education and
      the wider midwifery profession in recognising and maintaining practice consistent
      with the underlying philosophy of woman centred care.

PMID- 27865818
TI  - Maternity high-dependency care and the Australian midwife: A review of the
      literature.
AB  - BACKGROUND: Maternity high-dependency care has emerged throughout the 21st
      century in Australian maternity hospitals as a distinct sub-speciality of
      maternity care. However, what the care involves, how and why it should be
      provided, and the role of midwives in the provision of such care remains highly
      variable. INTRODUCTION: Rising levels of maternal morbidity from non-obstetric
      causes have led midwives to work with women who require highly complex care,
      beyond the standard customary midwifery role. Whilst the nursing profession has
      developed and refined its expertise as a specialty in the field of high
      dependency care, the midwifery profession has been less likely to pursue this as
      a specific area of practice. DISCUSSION: This paper explores the literature
      surrounding maternity high-dependency care. From the articles reviewed, four key
      themes emerge which include; the need for maternity high-dependency care,
      maternal morbidity and maternity high-dependency care, the role of the midwife
      and maternity high-dependency care and midwifery education and preparation for
      practice. It highlights the challenges that health services are faced with in
      order to provide maternity high-dependency care to women. Some of these
      challenges include resourcing and budgeting limitations, availability of
      educators with the expertise to train staff, and the availability of suitably
      trained staff to care for the women when required. CONCLUSION: In order to
      provide maternity high-dependency care, midwives need to be suitably equipped
      with the knowledge and skills required to do so.

PMID- 27865819
TI  - Buzz Juice: Neurological sequelae of synthetic cannabinoids.
AB  - The use of synthetic cannabinoids is becoming more widespread. Familiarity with
      the potential toxicities associated with these agents will grow in importance. We
      present a case of a woman who developed onset of confusion, visual
      hallucinations, and ataxia after vaporizing synthetic cannabinoids. MRI imaging
      demonstrated restricted diffusion and increased T2/FLAIR signal in the corpus
      callosum and cerebellar peduncles.

PMID- 27865820
TI  - Adjacent segment disease requiring reoperation in cervical total disc
      arthroplasty: A literature review and update.
AB  - OBJECTIVE: To evaluate the difference in rate of reoperation for adjacent segment
      disease (ASD) between anterior cervical decompression and fusion (ACDF) and total
      disc replacement (TDR). METHOD: A systematic review of literature was performed
      using PubMed, clinicaltrials.gov, and various other search engines. Nine studies
      met the inclusion criteria and were used to report an estimated overall rate of
      reoperation secondary to ASD for both ACDF and TDR. RESULTS: Forty-six clinical
      trials were identified after the initial search, and 9 studies met our inclusion
      criteria. Although the data was not pooled due to significant variation in level
      of evidence and length of follow-up, the overall rate of reoperation for ASD in
      the TDR cohort of patients analyzed in our review was 3.1% (range: 0-7.1%) with a
      follow-up between 24 and 80months. In contrast, the reoperation rate for ASD in
      the ACDF control was 6.0% (range: 1.0-11.9%). CONCLUSION: The average reoperation
      rate for ASD was 3.1% for the TDR across all studies, which was lower than the
      reoperation rate of 6.0% in the ACDF group. Further studies and follow-up data
      are still needed to determine if cervical TDR preserves adjacent segment motion
      more efficiently than the natural history of the disease, and if it will be a
      durable option when compared to the already excellent results of ACDF.

PMID- 27865821
TI  - The effects of tumor treating fields and temozolomide in MGMT expressing and non
      expressing patient-derived glioblastoma cells.
AB  - A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the
      addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined
      radiation/TMZ significantly increased survival and progression free survival.
      Preliminary data suggested benefit with both methylated and unmethylated O-6
      methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however,
      there have been no studies to address the potential interactions of TTFields and
      TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient
      derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12.1
      and 22GSC) and non-MGMT expressing (TMZ sensitive: 33 and 114GSC) lines. Dose
      response curves were constructed using cell proliferation and sphere-forming
      assays. Results demonstrated a ?10-fold increase in TMZ resistance of MGMT
      expressing (12.1GSCs: IC50=160MUM; 22GSCs: IC50=44MUM) compared to MGMT non
      expressing (33GSCs: IC50=1.5MUM; 114GSCs: IC50=5.2MUM) lines. TTFields inhibited
      12.1 GSC proliferation at all tested doses (50-500kHz) with an optimal frequency
      of 200kHz. At 200kHz, TTFields inhibited proliferation and tumor sphere formation
      of both MGMT GSC subtypes at comparable levels (12.1GSC: 74+/-2.9% and 38+/-3.2%,
      respectively; 22GSC: 61+/-11% and 38+/-2.6%, respectively; 33GSC: 56+/-9.5% and
      60+/-7.1%, respectively; 114 GSC: 79+/-3.5% and 41+/-4.3%, respectively). In
      combination, TTFields (200kHz) and TMZ showed an additive anti-neoplastic effect
      with equal efficacy for TTFields in both cell types (i.e., +/- MGMT expression)
      with no effect on TMZ resistance. This is the first demonstration of the effects
      of TTFields on cancer stem cells. The expansion of such studies may have clinical
      implications.

PMID- 27865822
TI  - Ambulatory blood pressure in hypertensive patients with inclusion criteria for
      the SPRINT trial.
AB  - We aimed to characterize 24-hour blood pressure (BP) values and categories in
      patients with inclusion/exclusion criteria of the Systolic Blood Pressure
      Intervention (SPRINT) trial from the Spanish ABPM Registry. We selected patients
      older than 50 years, with office systolic BP (SBP) above 130 mm Hg and at high
      cardiovascular risk, but without diabetes, previous stroke, or symptomatic heart
      failure. Ambulatory BP was compared among BP categories. A total of 39,132
      patients (34%) fulfilled inclusion criteria of SPRINT trial. Ambulatory SBP was
      considerably lower than office BP, with 42% of patients having daytime values
      below 130 mm Hg and 21% 24-hour values below 120 mm Hg. In conclusion, more than
      one-third of the hypertensive population included in the Spanish ABPM Registry
      can be considered as SPRINT candidates, although one out of five have values of
      24-hour SBP below 120 mm Hg. These data suggest that knowledge of ABPM values
      could be helpful when planning a treatment intensification in high-risk patients.

PMID- 27865823
TI  - Gut hormones and gut microbiota: implications for kidney function and
      hypertension.
AB  - Increased blood pressure (BP) and chronic kidney disease are two leading risk
      factors for cardiovascular disease. Increased sodium intake is one of the most
      important risk factors for development of hypertension. Recent data have shown
      that gut influences kidney function and BP by variety of mechanisms. Various
      hormones and peptides secreted from gut such as gastrin, glucocorticoids,
      Glucagon-like peptide-1 impact on kidney function and BP especially influencing
      sodium absorption from gut. These findings stimulate scientist to find new
      therapeutic options such as tenapanor for treatment of hypertension by blocking
      sodium absorption from gut. The gastrointestinal tract is also occupied by a huge
      community of microbes (microbiome) that under normal condition has a symbiotic
      relationship with the host. Alterations in the structure and function of the gut
      microbiota have been shown to play a key role in the pathogenesis and
      complications of numerous diseases including hypertension. Based on these data,
      in this review, we provide a summary of the available data on the role of gut and
      gut microbiota in regulation of BP and kidney function.

PMID- 27865824
TI  - Effect of placebo groups on blood pressure in hypertension: a meta-analysis of
      beta-blocker trials.
AB  - Hypertension is often treated pharmacologically. Since there is evidence that the
      cardiovascular system is sensitive to placebo mechanisms, our aim was to conduct
      an effect size analysis of placebo groups in double-blinded randomized controlled
      parallel-group drug trials using beta-blockers to treat hypertensive patients. A
      comprehensive literature search via PubMed, PsycINFO, PSYNDEX, PQDT OPEN,
      OpenGREY, ISI Web of Knowledge, and the WHO International Clinical Trials
      Registry Platform provided the basis of our meta-analysis. Effect sizes were
      estimated using a random-effects model based on 23 studies covering a total of
      11,067 participants. Main outcomes were systolic blood pressure (sBP) and
      diastolic blood pressure (dBP). Blood pressure was lowered in placebo groups with
      significant and robust effect sizes (Hedges' g). The estimates for sBP (-0.27, P
      < .001) and dBP (-0.49, P < .001) can be interpreted as small to moderate. The
      placebo response accounted for 34% of the drug response for sBP and 47% of the
      drug response for dBP. Our moderator analyses indicated that a higher study
      quality and more study site visits were marginally associated with a higher
      placebo response. In light of these strong placebo responses, placebo mechanisms
      need to be considered in order to improve antihypertensive treatment.

PMID- 27865825
TI  - Removal of protein S1 from Escherichia coli ribosomes without the use of affinity
      chromatography.
AB  - The paper reports an inexpensive and efficient procedure for the removal of
      protein S1 from E. coli ribosomes. It comprises incubation of ribosomes in a
      pyrimidine polyribonucleotide solution followed by centrifugation of the sample
      through a sucrose cushion. To avoid co-sedimentation of the S1-bound
      polypyrimidine with the ribosomes, its length should not exceed several hundred
      nucleotides. Unlike popular affinity chromatography through a poly(U) Sepharose
      or poly(U) cellulose column, the method tolerates limited polyribonucleotide
      degradation by eventual traces of ribonucleases, and can readily be incorporated
      into standard protocols for the isolation of ribosomes by centrifugation.

PMID- 27865826
TI  - Heavy menstrual bleeding in women treated with rivaroxaban and vitamin K
      antagonists and the risk of recurrent venous thromboembolism.
AB  - Anticoagulants increase the risk of heavy menstrual bleeding (HMB). We sought to
      investigate the incidence, predictors and management of HMB in women on
      rivaroxaban compared to those on vitamin K antagonists (VKA). We addressed the
      issue as to whether HMB is associated with VTE recurrences. We performed a single
      center prospective study in menstruating women aged 18-55years treated with
      rivaroxaban or VKA>=3months since the index VTE episode. Seventy six women on
      rivaroxaban and 45 patients on VKA were included. Patients on rivaroxaban more
      commonly reported HMB compared with those on VKA (31 [41%] vs. 8 [18%], p=0.009).
      Women treated with rivaroxaban more frequently needed interventions to reduce
      menstruation compared with those on VKA (29 [38%] vs. 6 [13%], p=0.004). During
      the median follow-up time of 13months, there were 8 (11%) recurrent VTE on
      rivaroxaban and 3 (7%) on VKA (p=0.5). Rivaroxaban treatment predisposed to HMB
      (odds ratio [OR] 3.2, 95% [confidence interval] CI 1.4-8.2, p=0.007) and the
      interruption of anticoagulant treatment for 2-3days (OR 3.2, 95% CI 1.1-11.6,
      p=0.033). HMB during the rivaroxaban treatment predisposed to recurrent VTE (OR
      5.3, 95% CI 1.1-33.3, p=0.038). In menstruating women following VTE, rivaroxaban
      is associated with a two-fold higher risk of HMB compared with VKA. HMB
      predisposes to recurrent VTE episode, most likely due to the short interruptions
      of anticoagulation.

PMID- 27865827
TI  - Overexpression of heat shock GroEL stress protein in leptospiral biofilm.
AB  - Leptospira is the causative agent of leptospirosis, which is an emerging zoonotic
      disease. Recent studies on Leptospira have demonstrated biofilm formation on
      abiotic surfaces. The protein expressed in the biofilm was investigated by using
      SDS-PAGE and immunoblotting in combination with MALDI-TOF mass spectrometry. The
      proteins expressed in Leptospira biofilm and planktonic cells was analyzed and
      compared. Among these proteins, one (60 kDa) was found to overexpress in biofilm
      as compared to the planktonic cells. MALDI-TOF analysis identified this protein
      as stress and heat shock chaperone GroEL. Our findings demonstrate that GroEL is
      associated with Leptospira biofilm. GroEL is conserved, highly immunogenic and a
      prominent stress response protein in pathogenic Leptospira spp., which may have
      clinical relevance.

PMID- 27865829
TI  - Trend and geographic analysis of the prevalence of dengue in Taiwan, 2010-2015.
AB  - BACKGROUND: Dengue is the most rapidly spreading disease caused by a mosquito
      borne virus in the world. The incidence of dengue globally has increased 30-fold
      in the last 50 years. Understanding the prevalence of dengue and its longitudinal
      trends can improve prevention and control strategies. This study assessed the
      trends in prevalence of dengue in Taiwan by population characteristics and
      geographical region. METHODS: Dengue and population data for the years 2010-2015
      were obtained from the public statistics databases of the Taiwan Centers for
      Disease Control and Department of Statistics, Taiwan Ministry of Interior. Yearly
      prevalence rates of dengue were calculated by age group, sex, and administrative
      area within five geographic regions (northern, mid-western, southern, and eastern
      regions, and outer islands). RESULTS: The national prevalence rate of dengue
      decreased gradually from 8 to 4 per 100000 population between 2010 and 2013, but
      it increased substantially in 2014 and 2015 to 67 and 187 per 100000 population,
      respectively. There was no significant difference in prevalence rate between
      males and females. People aged 60-69 years had a significantly higher prevalence
      rate than those in the other age groups during 2010-2014, and people aged over 70
      years had the highest rate in 2015 (309 per 100000 population). The southern
      region had the highest yearly dengue prevalence rate (the rate decreased from 23
      to 9 per 100000 population between 2010 and 2013, but increased to 220 and 616
      per 100000 population in 2014 and 2015, respectively). Three unexpected outbreaks
      of dengue were observed during the study period: the first outbreak occurred in
      Penghu County in 2011 (prevalence rate 101 per 100000 population), the second in
      Kaohsiung City in 2014 (prevalence rate 540 per 100000 population), and the third
      in Tainan City in 2015 (prevalence rate 1208 per 100000 population). CONCLUSIONS:
      More efforts are still needed to prevent and control dengue in Taiwan. The
      government should direct resources and interventions to southern Taiwan, which
      has a tropical climate and a high population density, and should target older
      people who are more likely to be infected. Strategies are also needed to respond
      quickly to unexpected incidents to prevent dengue outbreaks.

PMID- 27865828
TI  - Associations between former exposure to manganese and olfaction in an elderly
      population: Results from the Heinz Nixdorf Recall Study.
AB  - Occupational exposure to manganese (Mn) has been associated with impairments in
      olfaction and motor functions, but it has yet to be determined if such effects
      persist upon cessation of exposure. The objective of this study was to evaluate
      the influence of former occupational Mn exposure on olfaction within the
      framework of a prospective cohort study among an elderly German population.
      Information on job tasks with recognized Mn exposure and data on odor
      identification assessed with Sniffin' sticks was collected during the second
      follow-up of the Heinz Nixdorf Recall Study. The study population consisted of
      1385 men aged 55-86 years, 354 of whom ever worked in jobs with potential Mn
      exposure (median 58.3MUg/m3 years, interquartile range 19.0-185MUg/m3 years).
      Multiple exposure measures, including job tasks, cumulative Mn exposure, and Mn
      determined in blood samples (MnB) archived at baseline, were used to estimate
      effects of Mn on olfaction. Having ever worked as welder was associated with
      better olfaction compared to other blue-collar workers without Mn exposure. Blue
      collar workers identified less odors in comparison to white-collar workers.
      Concentrations of previous Mn exposure >185MUg/m3 years or MnB >=15MUg/L were not
      associated with impaired olfaction. In addition to a strong age effect,
      participants with lower occupational qualification identified less odors. We
      found no relevant association of former Mn exposure at relatively low levels with
      impaired olfaction. Possible neurotoxic Mn effects may not be persistent after
      cessation.

PMID- 27865830
TI  - Community-onset extended-spectrum-beta-lactamase-producing Escherichia coli
      sequence type 131 at two Korean community hospitals: The spread of multidrug
      resistant E. coli to the community via healthcare facilities.
AB  - BACKGROUND: The recent molecular epidemiology of ESBL-producing Escherichia coli
      infection in two Korean community hospitals was evaluated in this prospective
      observational study. METHODS: We collected non-duplicated E. coli isolates from
      consecutive, sequentially encountered patients with community-onset episodes
      between March and April 2016 in two community hospitals in Gyeonggi-do province,
      Korea. We studied the prevalence, clinical characteristics and molecular
      epidemiology of E. coli sequence type 131 (ST131) isolated from the community.
      RESULTS: From a total of 213 E. coli isolates collected from the community, 94
      (44.1%) were community-onset healthcare-associated isolates and 119 (55.9%) were
      community-associated isolates, of which urinary tract infection was the majority.
      A total of 55 (25.8%) of the 213 E. coli isolates were confirmed to have ESBL
      genes, which were mainly CTX-M types such as CTX-M-14 and CTX-M-15. There was no
      difference in the proportion of globally epidemic ST131 clones or that of O25,
      O16, H30, or H30Rx subclones between community-associated and community-onset
      healthcare-associated isolates. CONCLUSIONS: In this study, considerable ST131 E.
      coli isolations in the community were observed and about half of them were
      related to the history of a visit to the healthcare facilities, indicating the
      spread of multidrug-resistant E. coli to the community via healthcare facilities.

PMID- 27865831
TI  - Rutin suppresses human-amylin/hIAPP misfolding and oligomer formation in-vitro,
      and ameliorates diabetes and its impacts in human-amylin/hIAPP transgenic mice.
AB  - Pancreatic islet beta-cells secrete the hormones insulin and amylin, and
      defective beta-cell function plays a central role in the pathogenesis of type-2
      diabetes (T2D). Human amylin (hA, also termed hIAPP) misfolds and forms amyloid
      aggregates whereas orthologous mouse amylin does neither. Furthermore, hA elicits
      apoptosis in cultured beta-cells and beta-cell death in ex-vivo islets. In
      addition, hA-transgenic mice that selectively express hA in their beta-cells,
      manifest beta-cell apoptosis and progressive islet damage that leads to diabetes
      closely resembling that in patients with T2D. Aggregation of hA is thus linked to
      the causation of diabetes. We employed time-dependent thioflavin-T spectroscopy
      and ion-mobility mass spectrometry to screen potential suppressors of hA
      misfolding for anti-diabetic activity. We identified the dietary flavonol rutin
      as an inhibitor of hA-misfolding and measured its anti-diabetic efficacy in hA
      transgenic mice. In vitro, rutin bound hA, suppressed misfolding, disaggregated
      oligomers and reverted hA-conformation towards the physiological. In hA
      transgenic mice, measurements of glucose, fluid-intake, and body-weight showed
      that rutin-treatment slowed diabetes-progression by lowering of rates of
      elevation in blood glucose (P = 0.030), retarding deterioration from symptomatic
      diabetes to death (P = 0.014) and stabilizing body-weight (P < 0.0001). In
      conclusion, rutin treatment suppressed hA-aggregation in vitro and doubled the
      lifespan of diabetic mice (P = 0.011) by a median of 69 days compared with
      vehicle-treated control-diabetic hA-transgenic mice.

PMID- 27865832
TI  - Establishment of monoclonal antibodies against cell surface domains of
      ASCT2/SLC1A5 and their inhibition of glutamine-dependent tumor cell growth.
AB  - Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major
      transporter of the amino acid glutamine that is known to be overexpressed in
      certain malignant tumors. In this study, we generated specific monoclonal
      antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese
      hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008,
      KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these
      specifically bound to ASCT2-positive cells, as determined by flow cytometry and
      immunoprecipitation. In addition, the antibodies suppressed glutamine-dependent
      growth of WiDr colorectal cancer cells. These results provide evidence supporting
      the use of MAbs against ASCT2 as an effective therapeutic strategy for cancer
      treatment.

PMID- 27865833
TI  - Defects in the ratio of the dynein isoform, DHC11 in the long-flagella mutants of
      Chlamydomonas reinhardtii.
AB  - The long-flagella mutants (lf1, lf2, lf3 and lf4) of Chlamydomonas reinhardtii
      are defective in proteins that are required for the assembly of normal flagella,
      their phenotype being long flagella. In a previous study, we biophysically
      characterized these mutants for their waveform patterns, swimming speeds, beat
      frequencies and correlated these parameters with their flagellar lengths. We
      found an anomaly in this correlation and set out to explore the underlying
      molecular significance, if any. The diverse inner dynein isoforms are the
      flagellar motors that convert the chemical energy of ATP into the mechanical
      energy of motility; we probed the presence of one of these isoforms (DHC11, which
      might help in bend initiation) in the lf mutants and compared it with the wild
      type. Our studies show that the ratio of DHC11 is defective in the long-flagella
      mutants of Chlamydomonas reinhardtii.

PMID- 27865834
TI  - Expression and characterization of the Plasmodium translocon of the exported
      proteins component EXP2.
AB  - The malaria parasite Plasmodium falciparum requires the Plasmodium translocon of
      exported proteins (PTEX) to proliferate in human red blood cells. During the
      blood stages of malaria, several hundred parasite-encoded proteins are exported
      from the parasite into the cytosol of red blood cells. PTEX is the translocon for
      protein export and comprises 5 proteins: EXP2, PTEX150, PTEX88, Hsp101 and TRX2.
      Among them, EXP2 is thought to constitute the transmembrane pore, whereas the
      other components seem to play a role in unfolding the luggage proteins or
      providing a driving force. However, detailed functional and structural
      characterizations of PTEX proteins have not been performed. In this study, we
      expressed and characterized the membrane-associated component EXP2. Because
      expression of EXP2 is lethal to E. coli, EXP2 was expressed as a fusion protein
      with GST, and the recombinant EXP2 was obtained by protease digestion. The
      recombinant EXP2 formed pores in bilayer lipid membranes. The inner diameter of
      the pore was estimated to be approximately 3.5 nm based on electron microscopy
      images and channel currents. From this size and the molecular mass as determined
      by size exclusion chromatography and blue native polyacrylamide gel
      electrophoresis, we determined that the pore comprises approximately 10-12 EXP2
      subunits. However, there is a possibility that the pore structure is different in
      the PTEX complex. These results provide important insights in the protein
      transport mechanism of PTEX, which will aid in developing new drugs targeting
      PTEX.

PMID- 27865835
TI  - Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl
      and 2-pyrazoline derivatives of chalcones.
AB  - Super-activation of cholinesterases (acetylcholinesterase and
      butyrylcholinesterase) are linked to various neurological problems most precisely
      Alzheimer's disease (AD), which leads to senile dementia. Therefore,
      cholinesterases (AChE & BChE) inhibition are considered as a promising strategy
      for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of
      AD, belong to a group of cholinesterase inhibitors. However, none of them is able
      to combat or completely abrogate the disease progression. Herein, we report a
      series of newly synthesized chalcone derivatives with anti-AD potential. For this
      purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones
      were tested for their cholinesterases (AChE & BChE) inhibitory activity. All
      compounds were found as selective inhibitor of AChE. In piperidyl chalcones
      derivatives compound 1e having IC50 of 0.16 +/- 0.008 MUM and 2m in 2-pyrazoline
      chalcones with IC50 of 0.13 +/- 0.006 MUM, were found to be the most potent
      inhibitors of AChE, exhibiting ~142 and ~ 173-fold greater inhibitory potential
      compared to the reference inhibitor i.e., Neostigmine (IC50 +/- SEM = 22.2 +/-
      3.2 MUM). Molecular docking studies of most potent inhibitors were carried out to
      investigate the binding interactions inside the active site. Molecular docking
      study revealed that potent compounds and co-crystalized ligand had same binding
      orientation within the active site of target enzyme. Most of these compounds are
      selective inhibitors of AChE with a potential use against progressive
      neurodegenerative disorder and age related problems.

PMID- 27865836
TI  - G protein coupled receptor kinase-2 upregulation causes kappa-opioid receptor
      desensitization in diabetic heart.
AB  - Activation of kappa-opioid receptor (KOR) ameliorates myocardial
      ischemia/reperfusion (I/R) injury; however, cardioprotective effects of KOR
      stimulation disappear in type 1 diabetic subjects with hyperglycemia. The
      molecular mechanisms underlying this phenomenon remain unknown. Here we found
      that KOR expression was obviously downregulated and KOR agonism-induced
      contractile-regulatory and cardioprotective effects were significantly impaired
      in hearts isolated from streptozotocin (STZ) injection-induced diabetic mice.
      These in vivo data identified cardiac KOR desensitization as a novel
      characteristic of the diabetic heart. In cultured cardiomyocytes, high glucose
      (HG) caused obvious KOR downregulation, accompanied by an upregulation of G
      protein coupled receptor kinase-2 (GRK2). We found that HG exposure increased the
      interaction between GRK2 and KOR. More importantly, HG-induced KOR downregulation
      was reversed by small interfering RNA (siRNA)-mediated GRK2 inhibition. GRK2
      knockdown also restored KOR agonism-mediated protection against simulated I/R
      injury in cardiomyocytes. These in vitro data revealed an essential role of GRK2
      in HG-induced KOR desensitization. Finally, cardiac-specific GRK2 knockdown by
      intramyocardial siRNA injection blocked KOR downregulation and restored
      contractile-regulatory and cardioprotective effects of KOR agonism in hearts of
      diabetic mice. In conclusion, these data for the first time demonstrate that GRK2
      upregulation is largely responsible for cardiac KOR desensitization in diabetic
      individuals, which provides novel insights into the management of myocardial I/R
      injury in patients with diabetes.

PMID- 27865837
TI  - Autophagy protects against cholesterol-induced apoptosis in pancreatic beta
      cells.
AB  - Autophagy is believed to play an important role in maintaining homeostasis in
      pancreatic beta-cells during insulin resistance. This study investigated the role
      of autophagy in beta-cell damage induced by cholesterol and its possible
      activation mechanism. Rat and mouse pancreatic beta-cell lines INS-1 and betaTC-6
      were incubated with cholesterol alone or in combination with autophagy inhibitors
      E-64d/Pepstatin A or bafilomycin A1. DAPI staining, western blotting,
      transmission electron microscopy and immunofluorescence were conducted to assess
      the effects of autophagy inhibitors on cholesterol-induced apoptosis and
      autophagy activity. An increase in FITC-LC3 fluorescence dots, autophagic
      vacuoles and LC3-II protein indicated that autophagy was activated in cells
      treated with cholesterol. This was further confirmed by blocking the natural
      turnover processes in lysosomes and autolysosomes with autophagy inhibitors,
      suggesting enhanced autophagic activity rather than blockage of autophagy.
      Furthermore, inhibition of autophagy significantly augmented the activation of
      caspase 3 and the percentage of cholesterol-induced apoptotic nuclei. These
      results demonstrate that autophagy plays a protective role against cholesterol
      induced apoptosis in pancreatic beta-cells.

PMID- 27865839
TI  - Angiogenic factor with G patch and FHA domains 1 (Aggf1) promotes hepatic
      steatosis in mice.
AB  - Increased uptake of nutrients coupled with reduced activity leads to the
      development of a host of metabolic disorders in humans. In the present study we
      examined the role of angiogenic factor with G patch and FHA domains 1 (Aggf1) in
      the pathogenesis of steatosis, characterized by accumulation of lipids in the
      liver and consequently hepatic insulin resistance. We report here that Aggf1
      expression was up-regulated in the liver in both genetically predisposed and diet
      induced mouse model of steatosis. Aggf1 expression was also stimulated by free
      fatty acids in primary hepatocytes. Over-expression of Aggf1 in mice promoted
      steatosis. On the contrary, Aggf1 depletion ameliorated steatosis in mice.
      Mechanistically, Aggf1 activated the expression of gluconeogenesis gene and
      skewed the insulin signaling pathway to induce insulin resistance. Taken
      together, our data suggest that Aggf1 plays a role in steatosis in vivo and as
      such may be a new target in the development of therapeutics solutions against
      steatosis.

PMID- 27865840
TI  - A pleckstrin homology-like domain is critical for F-actin binding and cofilin
      phosphatase activity of Slingshot-1.
AB  - Slingshot-1 (SSH1) is a protein phosphatase that specifically dephosphorylates
      and activates cofilin, an F-actin-severing protein. SSH1 binds to and co
      localizes with F-actin, and the cofilin-phosphatase activity of SSH1 is markedly
      increased by binding to F-actin. In this study, we performed a secondary
      structure analysis of SSH1, which predicted the existence of a pleckstrin
      homology (PH)-like domain in the N-terminal region of SSH1. SSH1 also contains a
      DEK-C domain in the N-terminal region. The N-terminal fragment of SSH1 bound to
      and co-localized with F-actin, but mutation at Arg-96 or a Leu-His-Lys (LHK)
      motif in the PH-like domain reduced this activity. Furthermore, mutation at Arg
      96 abrogated the cofilin-phosphatase activity of SSH1 in the presence of F-actin.
      These results suggest that the N-terminal PH-like domain plays a critical role in
      F-actin binding and F-actin-mediated activation of the cofilin-phosphatase
      activity of SSH1.

PMID- 27865838
TI  - Helix B surface peptide attenuates diabetic cardiomyopathy via AMPK-dependent
      autophagy.
AB  - BACKGROUND: Erythropoietin (EPO) has been reported to exert protective effects on
      a host of damaged tissues. However, the erythropoietic effect of this hormone can
      result in high risks of thrombosis, stroke, and hypertension, remarkably limiting
      the clinical use of EPO. Helix B surface peptide (HBSP) is a small peptide
      derived from the helix-B domain of EPO. Surprisingly, HBSP retains the tissue
      protective properties of EPO without altering the hematocrit. Thus, we evaluated
      the possible role of HBSP on diabetic cardiomyopathy. METHODS: Diabetes was
      induced in mice by intraperitoneal injections of streptozocin (STZ). Mice were
      randomly treated with normal saline or HBSP. Cardiac function, fibrosis,
      apoptosis, and myocardial mitochondrial morphology were examined. For in vitro
      experiments, H9C2 myoblast cells were randomly grouped as normal glucose (NG, 5
      mM), NG+HBSP (100 nM), high glucose (HG, 33 mM), HG+HBSP (100 nM), HG+HBSP+3
      methyladenine (3-MA, 10 mM), HG+rapamycin (Rapa, 100 nM), and HG+HBSP+Compound C
      (CC, 10 mM). Autophagosomes, LC3 dots, apoptosis and mitochondria membrane
      potential (MMP) of H9C2 cells were examined.The expressions of LC3, p62, p-AMPK
      (Thr172) and p-mTOR (Ser2448) were examined by Western blot. RESULTS: HBSP
      markedly improved cardiac function, attenuated cardiac interstitial fibrosis,
      inhibited myocardial apoptosis, and ameliorated mitochondrial ultrastructure in
      mice with diabetic cardiomyopathy. HG reduced autophagy in H9C2 cells. HBSP
      enhanced autophagy in HG-treated H9C2 cells. HBSP reduced the apoptosis index of
      HG-treated H9C2 cells. HBSP increased the MMP of HG-treated H9C2 cells. HBSP
      increased the levels of p-AMPK (Thr172), and reduced p-mTOR (Ser2448) in HG
      treated H9C2 cells, and the increase of p-AMPK (Thr172) was accompanied by the
      stimulation of autophagy. Autophagy inhibitor 3-MA and AMPK inhibitor CC
      mitigated HBSP-induced beneficial effect, whereas autophagy inducer Rapa
      alleviated the HG-induced cell apoptosis. CONCLUSIONS: HBSP attenuates diabetic
      cardiomyopathy via autophagy mediated by AMPK-dependent pathway. HBSP may be a
      potential therapeutic intervention for diabetic cardiomyopathy.

PMID- 27865841
TI  - Survivin does not influence the anti-apoptotic action of XIAP on caspase-9.
AB  - Survivin inhibits apoptosis in numerous tumor cell lines and has emerged as
      promising target for cancer therapy. The anti-apoptotic effect of survivin was
      attributed to a direct interaction with XIAP (X-linked inhibitor of apoptosis)
      and to an indirect effect, where survivin antagonizes the anti-XIAP action of
      Smac. The direct interaction is thought to lead to synergistic inhibition of
      caspase-9 and, at the same time, to enhanced stability of XIAP by reducing its
      auto-ubiquitination. Using recombinant proteins, we have investigated the
      influence of survivin on the inhibition of caspase-9 by XIAP in vitro. With a
      fluorescence-based assay for the apoptosome-stimulated activity of caspase-9, we
      show that survivin has no effect on the inhibition of caspase-9 by XIAP, neither
      in the presence nor in the absence of Smac. Employing analytical size exclusion
      chromatography (SEC) and analytical ultracentrifugation, we show that survivin
      does not physically interact with XIAP. We confirm in vitro that XIAP
      ubiquitinates itself in the presence of the appropriate recombinant enzymes and
      Mg2+-ATP and could show that survivin neither influences the kinetics nor the
      extent of XIAP's self-ubiquitination. Our results call for a revision of the
      current view of how survivin interferes with the mitochondrial pathway of
      apoptosis.

PMID- 27865842
TI  - Decreasing SMPD1 activity in BEAS-2B bronchial airway epithelial cells results in
      increased NRF2 activity, cytokine synthesis and neutrophil recruitment.
AB  - Niemann-Pick disease (NPD) type B is a rare autosomal recessive disease
      characterized by variable levels of impairment in sphingomyelin phosphodiesterase
      1 (SMPD1) activity. Lung involvement is the most important prognostic factor in
      NPD-B, with recurrent respiratory infections starting in infancy being the major
      cause of morbidity and mortality. We hypothesized that decreased SMPD1 activity
      impaired airway epithelium host defense response. SMPD1 activity was reduced
      using inducible shRNA. Surprisingly, decreasing SMPD1 activity by 50%, resulted
      in increased neutrophil recruitment, both at baseline and in response to
      bacterial stimulation. This correlated with elevated levels of cytokine mRNA
      shown to contribute to neutrophil recruitment in unstimulated (e.g. IL-8 and GRO
      alpha) and infected cells (e.g. IL-8, GRO-alpha, GM-CSF and CCL20). Instead of
      preventing the host defence responses, decreased SMPD1 activity results in an
      inflammatory response even in the absence of infection. Moreover, decreasing
      SMPD1 activity resulted in a pro-oxidative shift. Accordingly, expression of an
      inactive mutant, SMPD1[L225P] but not the WT enzyme increased activation of the
      antioxidant transcription factor NRF2. Therefore, decreasing SMPD1 activity by
      50% in airway epithelial cells, the equivalent of the loss of one allele, results
      in the accumulation of oxidants that activates NRF2 and a concomitant increased
      cytokine production as well as neutrophil recruitment. This can result in a
      chronic inflammatory state that impairs host defence similar to scenarios observe
      in other chronic inflammatory lung disease such as Chronic Obstructive Pulmonary
      Disease or Cystic Fibrosis.

PMID- 27865844
TI  - Perturbations of carotenoid and tetrapyrrole biosynthetic pathways result in
      differential alterations in chloroplast function and plastid signaling.
AB  - In this study, we used the biosynthetic inhibitors of carotenoid and tetrapyrrole
      biosynthetic pathways, norflurazon (NF) and oxyfluorfen (OF), as tools to gain
      insight into mechanisms of photooxidation in rice plants. NF resulted in
      bleaching symptom on leaves of the treated plants, whereas OF treatment developed
      a fast symptom of an apparent necrotic phenotype. Both plants exhibited decreases
      in photosynthetic efficiency, as indicated by Fv/Fm. NF caused severe disruption
      in thylakoid membranes, whereas OF-treated plants exhibited disruption of
      chloroplast envelope and plasma membrane. Levels of Lhca and Lhcb proteins in
      photosystem I (PSI) and PSII were reduced by photooxidative stress in NF- and OF
      treated plants, with a greater decrease in NF plants. The down-regulation of
      nuclear-encoded photosynthesis genes Lhcb and rbcS was also found in both NF- and
      OF-treated plants, whereas plastid-encoded photosynthetic genes including RbcL,
      PsaC, and PsbD accumulated normally in NF plants but decreased drastically in OF
      plants. This proposes that the plastids in NF plants retain their potential to
      develop thylakoid membranes and that photobleaching is mainly controlled by
      nuclear genes. Distinct photooxidation patterns between NF- and OF-treated plants
      developed differential signaling, which might enable the plant to coordinate the
      expression of photosynthetic genes from the nuclear and plastidic genomes.

PMID- 27865843
TI  - Methylation effect on IPT5b gene expression determines cytokinin biosynthesis in
      apple rootstock.
AB  - The molecular mechanism of dwarfing in the apple rootstock is poorly understood,
      and has been attributed to low root cytokinin biosynthesis levels. Here we
      identified differences in root trans-zeatin content and expression of cytokinin
      metabolic pathway genes between dwarfing and vigorous rootstocks. Specifically, a
      stable low expression of IPT5b was identified in the dwarfing rootstocks.
      Bisulfite sequencing showed that two CpG islands (CpG2 and CpG4) in the IPT5b
      promoter region showed higher methylation levels in the M9 rootstock (dwarfing)
      compared to the Mr (vigorous) rootstock. Furthermore, IPT5b expression increased
      when M9 rootstocks were treated with 5-azaC, a methylation blocker, indicating
      that methylation levels influence IPT5b expression. In conclusion, we found low
      IPT5b expression with high level methylations in promoter region, leading to poor
      root trans-zeatin biosynthesis in the M9 rootstock, which may induce dwarfing.

PMID- 27865845
TI  - Temporal Spatial and Metabolic Measures of Walking in Highly Functional
      Individuals With Lower Limb Amputations.
AB  - OBJECTIVE: To record the temporal spatial parameters and metabolic energy
      expenditure during walking of individuals with amputation, walking with advanced
      prostheses, and after completion of comprehensive rehabilitation compared with
      able-bodied persons. DESIGN: Cross-sectional. SETTING: Multidisciplinary
      comprehensive rehabilitation center. PARTICIPANTS: Severely injured UK military
      personnel with amputation and subsequent completion of their rehabilitation
      program (n=30; unilateral transtibial: n=10, unilateral transfemoral: n=10, and
      bilateral transfemoral: n=10) were compared with able-bodied persons (n=10) with
      similar age, height, and mass (P>.537). Total number of participants (N = 40).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Temporal spatial and
      metabolic energy expenditure data were captured during walking on level ground at
      a self-selected speed. RESULTS: The individuals with amputation were all men,
      with a mean age of 29+/-4 years and a mean New Injury Severity Score of 31+/-16.
      Walking speed, stride length, step length, and cadence of individuals with a
      unilateral transtibial or transfemoral amputation were comparable with able
      bodied persons, and only individuals with a bilateral transfemoral amputation had
      a significantly slower walking speed (1.12m/s, P=.025) and reduced cadence (96
      steps per minute, P=.026). Oxygen cost for individuals with a unilateral
      transtibial amputation (0.15mL/kg/m) was the same as for able-bodied persons
      (0.15mL/kg/m) and significantly increased by 20% (0.18mL/kg/m, P=.023) for
      unilateral transfemoral amputation and by 60% (0.24mL/kg/m, P<.001) for bilateral
      transfemoral individuals with amputation. CONCLUSIONS: The scientific literature
      reports a wide range of gait and metabolic energy expenditure across individuals
      with amputation. The results of this study indicate that individuals with
      amputation have a gait pattern which is highly functional and efficient. This is
      comparable with a small number of studies reporting similar outcomes for
      individuals with a unilateral transtibial amputation, but the results from this
      study are better than those on individuals with transfemoral amputations reported
      elsewhere, despite comparison with populations wearing similar prosthetic
      componentry. Those studies that do report similar outcomes have included
      individuals who have been provided with a comprehensive rehabilitation program.
      This suggests that such a program may be as important as, or even more important
      than, prosthetic component selection in improving metabolic energy expenditure.
      The data are made available as a benchmark for what is achievable in the
      rehabilitation of some individuals with amputations, but agreeably may not be
      possible for all amputees to achieve.

PMID- 27865846
TI  - Effectiveness of an Educational Physiotherapy and Therapeutic Exercise Program in
      Adult Patients With Hemophilia: A Randomized Controlled Trial.
AB  - OBJECTIVE: To assess the efficacy of an educational physiotherapy home exercise
      intervention for physical improvement, pain perception, quality of life, and
      illness behavior in patients with hemophilic arthropathy. DESIGN: Single-blind
      randomized controlled trial. SETTING: Home. PARTICIPANTS: Patients with
      hemophilia (N=20) were randomly allocated to an educational intervention group or
      to a control group. INTERVENTIONS: The educational intervention was performed
      every 2 weeks over a 15-week period, and home exercises were carried out once a
      day, 6 days a week, over the same period. MAIN OUTCOME MEASURES: Joint status was
      evaluated using the Gilbert scale; pain was assessed using the visual analog
      scale; illness behavior was evaluated using the Illness Behavior Questionnaire;
      and the perception of the quality of life was evaluated using the A36 Hemophilia
      QoL questionnaire. RESULTS: We observed significant differences in the
      intervention group and the control group for both quality of life and illness
      behavior. There was no significant improvement in joint status; however, an
      improvement was noted in terms of perception of pain in the ankle. CONCLUSIONS: A
      physiotherapy program based on educational sessions and home exercises can
      improve the perception of pain in patients with hemophilic arthropathy of the
      ankle. It improves some variables in the perception of the quality of life and
      illness behavior.

PMID- 27865848
TI  - Retinol dehydrogenase 13 deficiency diminishes carbon tetrachloride-induced liver
      fibrosis in mice.
AB  - Retinol dehydrogenase 13 (RDH13) is a mitochondrion-localized member of the short
      chain dehydrogenases/reductases (SDRs) superfamily that participates in
      metabolism of some compounds. Rdh13 mRNA is most highly expressed in mouse liver.
      Rdh13 deficiency reduces the extent of liver injury and fibrosis, reduces hepatic
      stellate cell (HSC) activation, attenuates collagen I (II), tissue inhibitor of
      metalloproteinase 1 (TIMP-1) and transforming growth factor beta 1 (Tgf-beta1)
      expression. The results indicate an important role of Rdh13 and suggest RDH13 as
      a possible new therapeutic target for CCl4-induced fibrosis.

PMID- 27865849
TI  - Evaluation of existing (Q)SAR models for skin and eye irritation and corrosion to
      use for REACH registration.
AB  - The performance of the (Q)SAR models Derek Nexus, Toxtree and Case Ultra for the
      prediction of skin and eye irritation/corrosion is investigated. For irritation
      and corrosion of the skin, 117 compounds and for the eye, 125 compounds were
      listed. The balance between the groups positive and negative for irritation and
      corrosion was maintained. The obtained predictions were compared with
      experimental data and the numbers of true and false positives and negatives were
      determined. Based on these results several performance parameters of the tested
      (Q)SAR models were calculated. Despite all the efforts to make good and valid
      models, the results indicate a poor predictivity of the current models: a lot of
      compounds were not predicted, were out of the applicability domain or were
      predicted wrong. Considering our results, it can be concluded that the tested
      models are not yet sufficiently powerful for implementation. Possibly the
      training-sets used within the current models are not yet comprehensive enough or
      the incorporated data are not of enough quality. Although the use of these models
      as stand-alone evaluation is not recommended, these models can be of value as
      weight-of-evidence in the context of expert knowledge in an Integrated Approach
      to Testing and Assessment.

PMID- 27865847
TI  - Functional characterisation and application of an ex vivo perfusion-superfusion
      system in murine airways.
AB  - INTRODUCTION: The aim of this study was to develop two dynamic ex vivo airway
      explant systems, a perfusion-superfusion system and a ventilation-superfusion
      system, for the study of toxic airborne substances, such as the prevalent smoke
      constituent acrolein. METHODS: Mouse isolated tracheal segments were perfused
      with physiological media or ventilated with humidified air at 37 degrees C to
      mimic dynamic flow conditions, and superfused with media over the exterior
      surface. At selected time points, the histological and functional integrity of
      segments was evaluated. The perfusion-superfusion system was subsequently used to
      examine mucin secretory responses elicited by acrolein in airways in which mucous
      metaplasia had been induced with lipopolysaccharide (LPS; 1MUgml-1) prior to 24h
      of media perfusion, followed by stimulation with acrolein or ATP for 15min.
      Epithelial mucin levels were determined by quantitative analysis of periodic acid
      Schiff's reagent (PAS)-stained sections. RESULTS: Epithelial morphology was
      successfully preserved in the perfusion-superfusion and ventilation-superfusion
      systems for at least 24h and up to 18h, respectively. At these time points, the
      contractile and relaxation responses of perfused and ventilated tracheal segments
      to carbachol, the neuropeptide substance P, and the prostanoid PGE2 were also
      preserved. Using the perfusion-superfusion system, acute exposure to acrolein
      caused a dose-dependent reduction in the levels of PAS-positive mucin stores
      induced by LPS, consistent with mucin secretion. DISCUSSION: Both the perfusion
      superfusion and ventilation-superfusion systems successfully preserved the
      viability of mouse isolated tracheal segments on a histological and functional
      level, and the perfusion-superfusion system was used to characterise the mucin
      secretory responses elicited by acrolein. Thus, this system may be a useful model
      through which to conduct further toxicological studies in mammalian airways.

PMID- 27865850
TI  - Biopersistence and translocation to extrapulmonary organs of titanium dioxide
      nanoparticles after subacute inhalation exposure to aerosol in adult and elderly
      rats.
AB  - The increasing industrial use of nanoparticles (NPs) has raised concerns about
      their impact on human health. Since aging and exposure to environmental factors
      are linked to the risk for developing pathologies, we address the question of
      TiO2 NPs toxicokinetics in the context of a realistic occupational exposure. We
      report the biodistribution of titanium in healthy young adults (12-13-week-old)
      and in elderly rats (19-month-old) exposed to 10mg/m3 of a TiO2 nanostructured
      aerosol 6h/day, 5days/week for 4 weeks. We measured Ti content in major organs
      using inductively coupled plasma mass spectrometry immediately and up to 180days
      after the end of exposure. Large amounts of titanium were initially found in lung
      which were slowly cleared during the post-exposure period. From day 28, a small
      increase of Ti was found in the spleen and liver of exposed young adult rats.
      Such an increase was however never found in their blood, kidneys or brain. In the
      elderly group, translocation to extra-pulmonary organs was significant at day 90.
      Ti recovered from the spleen and liver of exposed elderly rats was higher than in
      exposed young adults. These data suggest that TiO2 NPs may translocate from the
      lung to extra-pulmonary organs where they could possibly promote systemic health
      effects.

PMID- 27865851
TI  - Pathological alpha-synuclein exacerbates the progression of Parkinson's disease
      through microglial activation.
AB  - Parkinson's disease (PD) is characterized by alpha-synuclein accumulation,
      dopaminergic neuron loss and inflammation. alpha-Synuclein can be secreted by
      neurons and activate microglia to different degrees. Excessive microglial
      activation can increase the production of tumor necrosis factor alpha (TNF
      alpha), interleukin-1-beta (IL-1beta), interleukin-6 (IL-6), interferon-gamma
      (INF-gamma), inducible nitric oxide synthase (iNOS), reactive oxygen species
      (ROS) and nitric oxide (NO), and can also enhance microglial phagocytosis and
      migration as well as lymphocyte infiltration. Pathological alpha-synuclein and
      microglial activation can potentiate each other, leading to the loss of
      dopaminergic neurons and accelerated PD degeneration. This review will mainly
      describe the profiles of alpha-synuclein-activated microglia, with particular
      emphasis on the signaling cascades involved in this process.

PMID- 27865852
TI  - Delivery methods for site-specific nucleases: Achieving the full potential of
      therapeutic gene editing.
AB  - The advent of site-specific nucleases, particularly CRISPR/Cas9, provides
      researchers with the unprecedented ability to manipulate genomic sequences. These
      nucleases are used to create model cell lines, engineer metabolic pathways,
      produce transgenic animals and plants, perform genome-wide functional screen and,
      most importantly, treat human diseases that are difficult to tackle by
      traditional medications. Considerable efforts have been devoted to improving the
      efficiency and specificity of nucleases for clinical applications. However, safe
      and efficient delivery methods remain the major obstacle for therapeutic gene
      editing. In this review, we summarize the recent progress on nuclease delivery
      methods, highlight their impact on the outcomes of gene editing and discuss the
      potential of different delivery approaches for therapeutic gene editing.

PMID- 27865854
TI  - Obeticholic acid protects against carbon tetrachloride-induced acute liver injury
      and inflammation.
AB  - The farnesoid X receptor (FXR) is a ligand-activated transcription factor that
      plays important roles in regulating bile acid homeostasis. The aim of the present
      study was to investigate the effects of obeticholic acid (OCA), a novel synthetic
      FXR agonist, carbon tetrachloride (CCl4)-induced acute liver injury. Mice were
      intraperitoneally injected with CCl4 (0.15ml/kg). In CCl4+OCA group, mice were
      orally with OCA (5mg/kg) 48, 24 and 1h before CCl4. As expected, hepatic FXR was
      activated by OCA. Interestingly, OCA pretreatment alleviated CCl4-induced
      elevation of serum ALT and hepatic necrosis. Moreover, OCA pretreatment inhibited
      CCl4-induced hepatocyte apoptosis. Additional experiment showed that OCA inhibits
      CCl4-induced hepatic chemokine gene Mcp-1, Mip-2 and Kc. Moreover, OCA inhibits
      CCl4-induced hepatic pro-inflammatory gene Tnf-alpha and Il-1beta. By contrast,
      OCA pretreatment elevated hepatic anti-inflammatory gene Il-4. Further analysis
      showed that OCA pretreatment inhibited hepatic IkappaB phosphorylation and
      blocked nuclear translocation of NF-kappaB p65 and p50 subunits during CCl4
      induced acute liver injury. In addition, OCA pretreatment inhibited hepatic Akt,
      ERK and p38 phosphorylation in CCl4-induced acute liver injury. These results
      suggest that OCA protects against CCl4-induced acute liver injury and
      inflammation. Synthetic FXR agonists may be effective antidotes for hepatic
      inflammation during acute liver injury.

PMID- 27865856
TI  - Melatonin-loaded silica coated with hydroxypropyl methylcellulose phthalate for
      enhanced oral bioavailability: Preparation, and in vitro-in vivo evaluation.
AB  - Melatonin (MLT) is a small molecule with low water solubility and high
      permeability. According to the Biopharmaceutics Classification System, MLT is a
      class II drug exhibiting a very short half-life and minimal and variable
      bioavailability. This work aimed to establish a delivery system composed of an
      enteric MLT nanosphere with favorably controlled and sustained release
      characteristics superior to those of raw MLT. The nanosphere was composed of
      hydroxypropyl methylcellulose phthalate (HP55) and silica (SiO2) with MLT. As a
      carrier, SiO2 contains numerous surface pores with high adsorption capacity
      advantageous for permeability and slow release. HP55 is a good enteric coating
      material. MLT-loaded SiO2 was obtained through adsorption in acetone solution. A
      MLT-loaded SiO2 coated with HP55 (MLT-SiO2-HP55) nanosphere was prepared via
      desolvation. The characteristics of this nanosphere were analyzed through
      transmission electron microscopy, Brunauer-Emmett-Teller surface area analysis,
      diffuse reflectance infrared Fourier transform spectroscopy, X-ray diffraction,
      differential scanning calorimetry, and thermogravimetric analysis. Results show
      that MLT was loaded mostly in the pores of SiO2. HP55 was coated on a large
      portion of MLT-SiO2. In vitro release studies revealed that the release rate of
      MLT from MLT-SiO2 was higher than that of raw MLT in simulated gastric fluid
      (SGF). The amount of MLT released from MLT-SiO2-HP55 in SGF was lower than that
      released from simulated intestinal fluid because of HP55 coated on MLT-SiO2. In
      vivo evaluation demonstrated the controlled drug release of MLT-SiO2-HP55 in
      rats. Compared with raw MLT, MLT-SiO2-HP55 prolonged peak time (Tmax) from 15min
      to 30min and increased peak concentration (Cmax) from 168.86ng/mL to 383.71ng/mL.
      The corresponding area under the curve (AUC) of MLT-SiO2-HP55 was 3.5 times
      higher than that of raw MLT. This finding illustrated the sustained release of
      MLT-SiO2-HP55. Our in vitro release and in vivo absorption studies indicated that
      the proposed preparation of MLT-SiO2-HP55 is an effective method to facilitate
      the controlled and sustained release of MLT with enhanced bioavailability.

PMID- 27865855
TI  - Intestinal response to salinity challenge in the Senegalese sole (Solea
      senegalensis).
AB  - Fish are continuously forced to actively absorb or expel water and ions through
      epithelia. Most studies have focused on the gill due to its role in Na+ and Cl-
      trafficking. However, comparatively few studies have focused on the changing
      function of the intestine in response to external salinity. Therefore, the
      present study investigated the main intestinal changes of long-term acclimation
      of the Senegalese sole (Solea senegalensis) to 5, 15, 38 and 55ppt. Through the
      measurement of short-circuit current (Isc) in Ussing chambers and biochemical
      approaches, we described a clear anterior/posterior functional regionalization of
      the intestine in response to salinity. The use of specific inhibitors in Ussing
      chamber experiments, revealed that the bumetanide-sensitive Na+/K+/Cl- co
      transporters are the main effectors of Cl- uptake in both anterior intestine and
      rectum. Additionally, the use of the anion exchanger specific inhibitor, DIDS,
      showed a salinity/region dependency of anion exchanger function. Moreover, we
      also described ouabain-sensitive Na+/K+-ATPase (NKA) and Bafilomycin A1-sensitive
      H+-ATPase activities (HA), which displayed changes related to salinity and
      intestinal region. However, the most striking result of the present study is the
      description of an omeprazole-sensitive H+/K+-ATPase (HKA) in the rectum of
      Senegalese sole. Its activity was consistently measurable and increased at lower
      salinities, reaching rates even higher than those of the NKA. Together our
      results provide new insights into the changing role of the intestine in response
      to external salinity in teleost fish. The rectal activity of HKA offers an
      alternative/cooperative mechanism with the HA in the final processing of
      intestinal water absorption by apical titration of secreted bicarbonate.

PMID- 27865857
TI  - Evaluation of dissolution profile similarity - Comparison between the f2, the
      multivariate statistical distance and the f2 bootstrapping methods.
AB  - A simulation study is presented, evaluating the performance of the f2, the model
      independent multivariate statistical distance and the f2 bootstrap methods in the
      ability to conclude similarity between two dissolution profiles. Different
      dissolution profiles, based on the Noyes-Whitney equation and ranging from
      theoretical f2 values between 100 and 40, were simulated. Variability was
      introduced in the dissolution model parameters in an increasing order, ranging
      from a situation complying with the European guidelines requirements for the use
      of the f2 metric to several situations where the f2 metric could not be used
      anymore. Results have shown that the f2 is an acceptable metric when used
      according to the regulatory requirements, but loses its applicability when
      variability increases. The multivariate statistical distance presented
      contradictory results in several of the simulation scenarios, which makes it an
      unreliable metric for dissolution profile comparisons. The bootstrap f2, although
      conservative in its conclusions is an alternative suitable method. Overall, as
      variability increases, all of the discussed methods reveal problems that can only
      be solved by increasing the number of dosage form units used in the comparison,
      which is usually not practical or feasible. Additionally, experimental corrective
      measures may be undertaken in order to reduce the overall variability,
      particularly when it is shown that it is mainly due to the dissolution assessment
      instead of being intrinsic to the dosage form.

PMID- 27865853
TI  - The principles and applications of avidin-based nanoparticles in drug delivery
      and diagnosis.
AB  - Avidin-biotin interaction is one of the strongest non-covalent interactions in
      the nature. Avidin and its analogues have therefore been extensively utilized as
      probes and affinity matrices for a wide variety of applications in biochemical
      assays, diagnosis, affinity purification, and drug delivery. Recently, there has
      been a growing interest in exploring this non-covalent interaction in nanoscale
      drug delivery systems for pharmaceutical agents, including small molecules,
      proteins, vaccines, monoclonal antibodies, and nucleic acids. Particularly, the
      ease of fabrication without losing the chemical and biological properties of the
      coupled moieties makes the avidin-biotin system a versatile platform for
      nanotechnology. In addition, avidin-based nanoparticles have been investigated as
      diagnostic systems for various tumors and surface antigens. In this review, we
      will highlight the various fabrication principles and biomedical applications of
      avidin-based nanoparticles in drug delivery and diagnosis. The structures and
      biochemical properties of avidin, biotin and their respective analogues will also
      be discussed.

PMID- 27865859
TI  - Solubilization of proteins in aqueous two-phase extraction through combinations
      of phase-formers and displacement agents.
AB  - The aqueous two-phase extraction (ATPE) of therapeutic proteins is a promising
      separation alternative to cost-intensive chromatography, still being the
      workhorse of nowadays downstream processing. As shown in many publications, using
      NaCl as displacement agent in salt-polymer ATPE allows for a selective
      purification of the target protein immunoglobulin G (IgG) from human serum
      albumin (HSA, represents the impurity). However a high yield of the target
      protein is only achievable as long as the protein is stabilized in solution and
      not precipitated. In this work the combined influence of NaCl and polyethylene
      glycol (Mw=2000g/mol) on the IgG-IgG interactions was determined using
      composition gradient multi-angle light scattering (CG-MALS) demonstrating that
      NaCl induces a solubilization of IgG in polyethylene glycol 2000 solution.
      Moreover it is shown that the displacement agent NaCl has a significant and
      beneficial influence on the IgG solubility in polyethyleneglycol2000-citrate
      aqueous two-phase system (ATPS) which can also be accessed by these advanced B22
      measurements. By simultaneous consideration of IgG solubility data with results
      of the ATPS phase behavior (especially volume fraction of the respective phases)
      allows for the selection of process tailored ATPS including identification of the
      maximum protein feed concentration. Through this approach an ATPS optimization is
      accessible providing high yields and selectivity of the target protein (IgG).

PMID- 27865858
TI  - Biodistribution of radiolabeled polyglutamic acid and PEG-polyglutamic acid
      nanocapsules.
AB  - Recently we reported the development of 100nm polyglutamic acid (PGA)-based
      nanocapsules, which were intended to carry anticancer drugs to the lymphatic
      system (Abellan-Pose et al., 2016). In this work, the objective was to further
      assess the potential "lympho-targeting" properties of radiolabeled 111In-PGA and
      111In-PGA-PEG, following intravenous or subcutaneous administration. The results
      indicate that, following intravenous administration, both types of nanocapsules
      exhibit a modest accumulation in the lymph nodes (?2.3% ID/g). On the contrary,
      following subcutaneous administration, and irrespective of the presence of PEG on
      their surface, the nanocapsules were found to form a reservoir at the injection
      site, from which they drained slowly into the popliteal and the iliac lymph
      nodes. The significant accumulation of the radiolabeled nanocapsules in the lymph
      nodes was attained at 24 and 48h post-injection, reaching values comprised
      between 70% and 187% ID/g in the popliteal lymph nodes. Altogether, the results
      led us to validate our hypothesis about the ability of the PGA and PGA-PEG
      nanocapsules to reach the lymphatic system, especially following subcutaneous
      administration.

PMID- 27865860
TI  - Human regulatory B cells control the TFH cell response.
AB  - BACKGROUND: Follicular helper T (TFH) cells support terminal B-cell
      differentiation. Human regulatory B (Breg) cells modulate cellular responses, but
      their control of TFH cell-dependent humoral immune responses is unknown.
      OBJECTIVE: We sought to assess the role of Breg cells on TFH cell development and
      function. METHODS: Human T cells were polyclonally stimulated in the presence of
      IL-12 and IL-21 to generate TFH cells. They were cocultured with B cells to
      induce their terminal differentiation. Breg cells were included in these
      cultures, and their effects were evaluated by using flow cytometry and ELISA.
      RESULTS: B-cell lymphoma 6, IL-21, inducible costimulator, CXCR5, and programmed
      cell death protein 1 (PD-1) expressions increased on stimulated human T cells,
      characterizing TFH cell maturation. In cocultures they differentiated B cells
      into CD138+ plasma and IgD-CD27+ memory cells and triggered immunoglobulin
      secretions. Breg cells obtained by Toll-like receptor 9 and CD40 activation of B
      cells prevented TFH cell development. Added to TFH cell and B-cell cocultures,
      they inhibited B-cell differentiation, impeded immunoglobulin secretions, and
      expanded Foxp3+CXCR5+PD-1+ follicular regulatory T cells. Breg cells modulated IL
      21 receptor expressions on TFH cells and B cells, and their suppressive
      activities involved CD40, CD80, CD86, and intercellular adhesion molecule
      interactions and required production of IL-10 and TGF-beta. CONCLUSION: Human
      Breg cells control TFH cell maturation, expand follicular regulatory T cells, and
      inhibit the TFH cell-mediated antibody secretion. These novel observations
      demonstrate a role for the Breg cell in germinal center reactions and suggest
      that deficient activities might impair the TFH cell-dependent control of humoral
      immunity and might lead to the development of aberrant autoimmune responses.

PMID- 27865861
TI  - Midpregnancy and cord blood immunologic biomarkers, HLA genotype, and pediatric
      celiac disease.

PMID- 27865862
TI  - Impaired mucus clearance exacerbates allergen-induced type 2 airway inflammation
      in juvenile mice.
AB  - BACKGROUND: Type 2 airway inflammation plays a central role in the pathogenesis
      of allergen-induced asthma, but the underlying mechanisms remain poorly
      understood. Recently, we demonstrated that reduced mucociliary clearance, a
      characteristic feature of asthma, produces spontaneous type 2 airway inflammation
      in juvenile beta-epithelial Na+ channel (Scnn1b)-transgenic (Tg) mice. OBJECTIVE:
      We sought to determine the role of impaired mucus clearance in the pathogenesis
      of allergen-induced type 2 airway inflammation and identify cellular sources of
      the signature cytokine IL-13. METHODS: We challenged juvenile Scnn1b-Tg and wild
      type mice with Aspergillus fumigatus and house dust mite allergen and compared
      the effects on airway eosinophilia, type 2 cytokine levels, goblet cell
      metaplasia, and airway hyperresponsiveness. Furthermore, we determined cellular
      sources of IL-13 and effects of genetic deletion of the key type 2 signal
      transducing molecule signal transducer and activator of transcription 6 (STAT6)
      and evaluated the effects of therapeutic improvement of mucus clearance. RESULTS:
      Reduced mucociliary allergen clearance exacerbated Stat6-dependent secretion of
      type 2 cytokines, airway eosinophilia, and airway hyperresponsiveness in juvenile
      Scnn1b-Tg mice. IL-13 levels were increased in airway epithelial cells,
      macrophages, type 2 innate lymphoid cells, and TH2 cells along with increased
      Il33 expression in the airway epithelium of Scnn1b-Tg mice. Treatment with the
      epithelial Na+ channel blocker amiloride, improving airway surface hydration and
      mucus clearance, reduced allergen-induced inflammation in Scnn1b-Tg mice.
      CONCLUSION: Our data support that impaired clearance of inhaled allergens
      triggering IL-13 production by multiple cell types in the airways plays an
      important role in the pathogenesis of type 2 airway inflammation and suggests
      therapeutic improvement of mucociliary clearance as a novel treatment strategy
      for children with allergen-induced asthma.

PMID- 27865863
TI  - Curcumin promotes the oncoltyic capacity of vesicular stomatitis virus for the
      treatment of prostate cancers.
AB  - Vesicular stomatitis virus (VSV) matrix (M) protein mutants have been studied as
      oncolytic agents due to their capacity to effectively kill cancer cells while
      exhibiting low virulence in vivo. Despite encouraging results, many cancer cells
      maintain resistance to oncolytic VSV mutants in part due to residual antiviral
      responses. We sought to determine whether combination of VSV with natural agents
      with anti-tumor properties, such as curcumin, resveratrol, and flavokavain B,
      would enhance tumor cell killing in a prostate cancer model. Our results revealed
      that pretreatment with curcumin potentiated VSV-induced oncolysis of PC-3
      prostate cancer cells in cell culture and in a mouse model of prostate cancer.
      The ability of curcumin to synergize with VSV in PC-3 cells correlated with a
      cumulative decrease in the expression of the anti-apoptotic protein, Bcl-xl, and
      in the phosphorylation of NF-kappaB. Although curcumin did not impact the
      expression of type I IFN in infected cells, it inhibited the phosphorylation and
      activation of STAT1, a key player in the IFN response pathway, leading to an
      overall increase in virus-infected cells. These results suggest that curcumin
      sensitizes prostate cancer cells to the oncolytic effects of VSV by modulating
      antiviral responses and components of the intrinsic apoptotic pathway.

PMID- 27865864
TI  - Construction and manipulation of a full-length infectious bacterial artificial
      chromosome clone of equine herpesvirus type 3 (EHV-3).
AB  - Equine herpesvirus type 3 (EHV-3) is the causal agent of equine coital exanthema,
      a disease characterized by pox-like lesions on the penis of stallions and the
      vulva of mares. Although the complete genomic sequence of EHV-3 has been recently
      made available, its genomic content remains poorly characterized and the
      molecular mechanisms of disease development not yet elucidated. In an attempt to
      facilitate genetic manipulation of EHV-3, we describe here the construction of a
      full-length infectious bacterial artificial chromosome (BAC) clone of EHV-3. Mini
      F vector sequences were inserted into the intergenic region between ORF19 and
      ORF20 (UL41 and UL40, respectively) of EHV-3 strain C175 by homologous
      recombination in equine dermal cells (NBL-6). DNA of the resulting recombinant
      virus was electroporated into E. coli and a full-length EHV-3 BAC clone was
      recovered. Virus reconstituted after transfection of the EHV-3 BAC into NBL-6
      cells showed growth properties in vitro that were indistinguishable from those of
      the parental virus. To assess the feasibility of mutagenesis of the cloned EHV-3
      genome, recombinant viruses targeting the glycoprotein E (gE) gene were generated
      using Red recombination in E. coli and in vitro growth properties of the
      recombinant viruses were evaluated. We first repaired the gE (ORF74) coding
      region, since the parental virus used for BAC cloning specifies a truncated
      version of the gene, and then created gE-tagged and gE-null versions of the
      virus. Our results demonstrated that: (i) EHV-3 can be efficiently cloned as a
      BAC allowing easy manipulation of its genome; (ii) gE is dispensable for EHV-3
      growth in vitro and is expressed as a product of approximately 110-kDa in
      infected cells; (iii) viruses having a deletion compromising gE expression or
      with a truncation of the cytoplasmic and transmembrane domains are significantly
      compromised with regard cell-to-cell spread. The cloning of EHV-3 as a BAC
      simplifies future studies to identify the role of its coding genes in viral
      pathogenesis and host immune responses.

PMID- 27865865
TI  - Ectromelia virus N1L is essential for virulence but not dissemination in a
      classical model of mousepox.
AB  - Mousepox is caused by the orthopoxvirus ectromelia virus (ECTV), and is thought
      to be transmitted via skin abrasions. We studied the ECTV virulence factor N1
      following subcutaneous infection of mousepox-susceptible BALB/c mice. In this
      model, ECTV lacking N1L gene was attenuated more than 1000-fold compared with
      wild-type virus and replication was profoundly reduced as early as four days
      after infection. However, in contrast to data from an intranasal model, N1
      protein was not required for virus dissemination. Further, neither T cell nor
      cytokine responses were enhanced in the absence of N1. Together with the early
      timing of reduced virus titres, this suggests that in a cutaneous model, N1
      exerts its function at the level of infected cells or in the inhibition of the
      very earliest effectors of innate immunity.

PMID- 27865866
TI  - Age-related differences in processes organizing goal-directed locomotion toward
      emotional pictures.
AB  - Previous studies yielded evidence for an interaction between age and valence in
      numerous cognitive processes. But, to date, no research has been conducted in the
      field of motor skills. In this study, we examined the age-related differences in
      the organization of an emotionally goal-directed locomotion task. Faced with a
      pleasant, unpleasant, or neutral picture displayed to the side of a stop button,
      younger and older adults were instructed to walk toward the button (intermediate
      goal) and push it to turn-off the picture (final goal). Kinematic and ground
      reaction forces were recorded. The main findings indicated that older adults'
      response times (RTs) did not differ across the valence picture. The fastest RTs
      were found in younger adults when faced with pleasant pictures, suggesting that
      older people may focus either on intermediate or final goals, depending on their
      value of pleasantness, and prioritize positive goals. We also found that the
      spatial coding of locomotion (trajectory and final body position) was affected in
      the same way by the valence of the intermediate goal in both age groups. Taken
      together, these findings provide new perspectives regarding the potential role of
      the emotional valence of the intermediate and final goals on the cognitive
      processes involved in action coding, such as in mental representations of action
      in older adults.

PMID- 27865867
TI  - D1-like dopamine receptor dysfunction in the lateral habenula nucleus increased
      anxiety-like behavior in rat.
AB  - Lateral habenula (LHb) is important for emotional processing. It is a link node
      between forebrain and midbrain. LHb is reciprocally connected with ventral
      tegmental area, acting as a regulatory center for the dopaminergic system.
      However, the role of dopamine receptors in the LHb in emotional processing is
      less clear. In the present study, the expression of dopamine D1 and D2 receptors
      in LHb was testified by western blot. In addition, D1- or D2-like receptor
      agonist or antagonist was bilaterally administered into the LHb, anxiety-like and
      depressive-like behaviors were tested 15min later in rats. In addition, the
      effects of LHb dopamine receptor activation and inactivation on aversive learning
      and memory were assessed. Our results showed that: (1) activation and inhibition
      of D1R but not D2R in LHb increased anxiety-like behavior but decreased
      depressive-like behavior in rats. (2) D1R activation and inactivation in LHb
      impaired aversive memory acquisition but not consolidation in rats, D1R agonist
      also impaired aversive memory retrieval in rats. These results might provide new
      clues about how LHb was involved in emotional processing.

PMID- 27865868
TI  - Blast-induced tinnitus and hyperactivity in the auditory cortex of rats.
AB  - Blast exposure can cause tinnitus and hearing impairment by damaging the auditory
      periphery and direct impact to the brain, which trigger neural plasticity in both
      auditory and non-auditory centers. However, the underlying neurophysiological
      mechanisms of blast-induced tinnitus are still unknown. In this study, we induced
      tinnitus in rats using blast exposure and investigated changes in spontaneous
      firing and bursting activity in the auditory cortex (AC) at one day, one month,
      and three months after blast exposure. Our results showed that spontaneous
      activity in the tinnitus-positive group began changing at one month after blast
      exposure, and manifested as robust hyperactivity at all frequency regions at
      three months after exposure. We also observed an increased bursting rate in the
      low-frequency region at one month after blast exposure and in all frequency
      regions at three months after exposure. Taken together, spontaneous firing and
      bursting activity in the AC played an important role in blast-induced chronic
      tinnitus as opposed to acute tinnitus, thus favoring a bottom-up mechanism.

PMID- 27865869
TI  - ERK potentiates p38 in central sensitization induced by traumatic occlusion.
AB  - This study was to investigate the role of p38 activation via ERK1/2
      phosphorylation in neurons and microglia of the spinal trigeminal subnucleus
      caudalis (Vc) in the promotion of orofacial hyperalgesia induced by unilateral
      anterior crossbite (UAC) traumatic occlusion in adult rats. U0126, a p-ERK1/2
      inhibitor, was injected intracisternally before UAC implant. The effects of the
      U0126 injection were compared to those following the injection of SB203580, a p
      p38 inhibitor. Mechanical hyperalgesia was evaluated via pressure pain threshold
      measurements. Brain stem tissues were processed for a Western blot analysis to
      evaluate the activation of ERK1/2 and p38. Double immunofluorescence was also
      performed to observe the expression of p-ERK1/2 and p-p38 in neurons (labeled by
      NeuN) and microglia (labeled by OX42). The data showed that UAC caused orofacial
      hyperalgia ipsilaterally on d1 to d7, peaking on d3 (P<0.05). An upregulation of
      p-ERK1/2 was observed in the ipsilateral Vc on d1 to d3, peaking on d1. An
      upregulation of p-p38 was also observed on d1 to d7, peaking on d3 (P<0.05). p
      ERK1/2 primarily co-localized with NeuN and, to a lesser extent, with OX42, while
      p-p38 co-localized with both NeuN and OX42. Pretreatment with U0126 prevented the
      upregulation of both p-ERK1/2 and p-p38. Similarly to an intracisternal injection
      of SB203580, U0126 pretreatment attenuated the UAC-induced orofacial
      hyperalgesia. These data indicate that UAC caused orofacial hyperalgesia by
      inducing central sensitization via the activation of ERK1/2 and p38 in both
      neurons and microglia in the Vc, potentially impacting the effects of p-ERK1/2
      during p38 activation.

PMID- 27865870
TI  - African and classical swine fever situation in Ivory-Coast and neighboring
      countries, 2008-2013.
AB  - This study was conducted from 2008 to 2013 to determine the animal health status
      of Ivory Coast and neighboring countries (Burkina Faso, Ghana, Togo and Benin)
      for African swine fever (ASF) and classical swine fever (CSF), and to assess the
      risk factors for ASF introduction in Ivory Coast. Ivory Coast had probably been
      free from ASF from 1998 to 2014 when it was re-introduced in this country.
      However, the ASF virus was found in all neighboring countries. In contrast, no
      evidence of CSF infection was found so far in Ivory Coast and neighboring
      countries. To assess the risk of ASF reintroduction in Ivory Coast, we surveyed
      59 modern pig farms, and 169 pig owners in 19 villages and in two towns. For the
      village livestock, the major risk factor was the high frequency of pig exchanges
      with Burkinabe villages. In the commercial sector, many inadequate management
      practices were observed with respect to ASF. Their identification should enable
      farmers and other stakeholders to implement a training and prevention program to
      reduce the introduction risk of ASF in their farms.

PMID- 27865872
TI  - Thymic Hyperplasia after Treatment of ACTH-Dependent Cushing's Syndrome Can Be
      Mistaken for a Thymic Epithelial Tumor.

PMID- 27865871
TI  - Clinical Impact of Hybrid Capture-Based Next-Generation Sequencing on Changes in
      Treatment Decisions in Lung Cancer.
AB  - INTRODUCTION: Targeted therapy significantly prolongs survival in lung
      adenocarcinoma. Current diagnostic guidelines include only EGFR and anaplastic
      lymphoma receptor tyrosine kinase gene (ALK) testing. Next-generation sequencing
      (NGS) reveals more actionable genomic alterations than do standard diagnostic
      methods. Data on the influence of hybrid capture (HC)-based NGS on treatment are
      limited, and we investigated its impact on treatment decisions and clinical
      outcomes. METHODS: This retrospective study included patients with advanced lung
      cancer on whom HC-based NGS was performed between November 2011 and October 2015.
      Demographic and clinicopathologic characteristics, treatments, and outcome data
      were collected. RESULTS: A total of 101 patients were included (median age 63
      years [53% females, 45% never-smokers, and 85% with adenocarcinoma]). HC-based
      NGS was performed upfront and after EGFR/ALK testing yielded negative or
      inconclusive results in 15% and 85% of patients, respectively. In 51.5% of
      patients, HC-based NGS was performed before first-line therapy, and in 48.5%, it
      was performed after treatment failure. HC-based NGS identified clinically
      actionable genomic alterations in 50% of patients, most frequently in EGFR (18%),
      Ret proto-oncogene (RET) (9%), ALK (8%), Mesenchymal-epithelial transition factor
      (MET) receptor tyrosine kinase gene (6%), and erb-b2 receptor tyrosine kinase 2
      gene (ERBB2) (5%). In 15 patients, it identified EGFR/ALK aberrations after
      negative results of prior standard testing. Treatment strategy was changed for 43
      patients (42.6%). The overall response rate in these patients was 65% (complete
      response 14.7%, partial response 50%). Median survival was not reached.
      Immunotherapy was administered in 33 patients, mostly without an actionable
      driver, with a presenting disease control rate of 32%, and with an association
      with tumor mutation burden. CONCLUSIONS: HC-based NGS influenced treatment
      decisions in close to half of the patients with lung adenocarcinoma and was
      associated with an overall response rate of 65%, which may translate into a
      survival benefit.

PMID- 27865873
TI  - Signaling via G proteins mediates tumorigenic effects of GPR87.
AB  - G protein-coupled receptors (GPCRs) constitute a large protein family of seven
      transmembrane (7TM) spanning proteins that regulate multiple physiological
      functions. GPR87 is overexpressed in several cancers and plays a role in tumor
      cell survival. Here, the basal activity of GPR87 was investigated in transiently
      transfected HEK293 cells, revealing ligand-independent coupling to Galphai,
      Galphaq and Galpha12/13. Furthermore, GPR87 showed a ligand-independent G protein
      dependent activation of the downstream transcription factors CREB, NFkappaB, NFAT
      and SRE. In tetracycline-induced Flp-In T-Rex-293 cells, GPR87 induced cell
      clustering presumably through Galpha12/13 coupling. In a foci formation assay
      using retrovirally transduced NIH3T3 cells, GPR87 showed a strong in vitro
      transforming potential, which correlated to the in vivo tumor induction in nude
      mice. Importantly, we demonstrate that the transforming potential of GPR87 was
      correlated to the receptor signaling, as the signaling-impaired mutant R139A (Arg
      in the conserved "DRY"-motif at the bottom of transmembrane helix 3 of GPR87
      substituted to Ala) showed a lower in vitro cell transformation potential.
      Furthermore, R139A lost the ability to induce cell clustering. In summary, we
      show that GPR87 is active through several signaling pathways and that the
      signaling activity is linked to the receptor-induced cell transformation and
      clustering. The robust surface expression of GPR87 and general high druggability
      of GPCRs make GPR87 an attractive future anticancer target for drugs that -
      through inhibition of the receptor signaling - will inhibit its transforming
      properties.

PMID- 27865875
TI  - Axillary migration of Nexplanon(r): Case report.
AB  - A 19-year-old patient presented to the clinic, and we inserted a single rod
      subdermal etonogestrel implant (Nexplanon (r)), which subsequently migrated to
      the ipsilateral axilla. Distant Nexplanon(r) migration is a rare serious
      complication that should be considered when a device is nonpalpable. Management
      options are discussed.

PMID- 27865874
TI  - Bromodomain-containing protein 2 induces insulin resistance via the mTOR/Akt
      signaling pathway and an inflammatory response in adipose tissue.
AB  - Insulin resistance is a major metabolic abnormality in a large majority of
      patients with type II diabetes. Bromodomain-containing protein 2 (Brd2), a
      transcriptional co-activator/co-repressor with switch mating type/sucrose non
      fermenting (SWI/SNF)-like functions that regulates chromatin, suppresses
      adipocyte differentiation and regulates pancreatic beta-cell biology. However,
      the effects of Brd2 on insulin resistance remain unknown. Here, overexpression of
      Brd2 in white adipose tissue of wild-type (WT) mice led to insulin resistance.
      Brd2 overexpression induced the expression of nuclear Factor-kappaBeta (NF
      kappaBeta) target genes, mainly involving proinflammatory and chemotactic
      factors, in adipocytes. Furthermore, it decreased the expression of DEP domain
      containing mTOR-interacting protein (Deptor) to enhance mechanistic target of
      rapamycin (mTOR) signaling, thus blocking insulin signaling. Collectively, these
      results provided evidence for a novel role of Brd2 in chronic inflammation and
      insulin resistance, suggesting its potential in improving insulin resistance and
      treating metabolic disorders.

PMID- 27865876
TI  - Interstitial Lung Disease in the Elderly.
AB  - BACKGROUND: Despite the relationship between idiopathic pulmonary fibrosis (IPF)
      and advancing age, little is known about the epidemiology of interstitial lung
      disease (ILD) in the elderly. We describe the diagnoses, clinical
      characteristics, and outcomes of patients who were elderly at the time of ILD
      diagnosis. METHODS: Among subjects from a prospective cohort study of ILD,
      elderly was defined as age >= 70 years. Diagnoses were derived from a
      multidisciplinary review. Differences between elderly and nonelderly groups were
      determined using the chi2 test and analysis of variance. RESULTS: Of the 327
      subjects enrolled, 80 (24%) were elderly. The majority of elderly subjects were
      white men. The most common diagnoses were unclassifiable ILD (45%), IPF (34%),
      connective tissue disease (CTD)-ILD (11%), and hypersensitivity pneumonitis (8%).
      Most elderly subjects (74%) with unclassifiable ILD had an imaging pattern
      inconsistent with usual interstitial pneumonia (UIP). There were no significant
      differences in pulmonary function or 3-year mortality between nonelderly and
      elderly subjects combined or in a subgroup analysis of those with IPF.
      CONCLUSIONS: Although IPF was the single most common diagnosis, the majority of
      elderly subjects had non-IPF ILD. Our findings highlight the need for every
      patient with new-onset ILD, regardless of age, to be surveyed for exposures and
      findings of CTD. Unclassifiable ILD was common among the elderly, but for most,
      the radiographic pattern was inconsistent with UIP. Although the effect of ILD
      may be more pronounced in the elderly due to reduced global functionality, ILD
      was not more severe or aggressive in this group.

PMID- 27865878
TI  - Bone marrow mesenchymal stem cells decrease CHOP expression and neuronal
      apoptosis after spinal cord injury.
AB  - Spinal cord injury (SCI) leads to irreversible neuronal loss and ultimately leads
      to paralysis. Bone marrow derived mesenchymal stem cells (BMSCs) have been
      demonstrated to be an effective approach to treat SCI. The present study was
      designed to investigate the role of BMSCs in rats with spinal cord injury and in
      oxygen-glucose deprivation (OGD) treated motor neurons. The results demonstrated
      that BMSCs could improve locomotor function and decrease expression of pro
      apoptotic transcription factor C/EBP homologous protein (CHOP) and apoptosis
      after SCI. Furthermore, co-culture with BMSCs or conditioned medium from BMSCs
      could also decrease the expression of CHOP and apoptosis in post-OGD motor
      neurons, supporting that BMSCs exerts protective effects by decreasing the
      expression of CHOP in injured motor neurons. Our findings provide a potential
      novel mechanism for BMSCs treatments in patients with SCI.

PMID- 27865879
TI  - Arachidonic acid has protective effects on oxygen-glucose deprived astrocytes
      mediated through enhancement of potassium channel TREK-1 activity.
AB  - Polyunsaturated fatty acids (PUFAs) have neuroprotective effects against ischemic
      brain diseases. The newly discovered potassium channel "TREK-1" is a promising
      target for therapies against neurodegeneration. Arachidonic acid (AA) is an n-6
      PUFA, as well as a potent TREK-1 activator. We previously showed that TREK-1 is
      expressed at high levels in astrocytes. However, the effect of AA on astrocytes
      in ischemia remains unknown. Here, we assessed the effects of 3-30MUM AA on
      astrocyte apoptosis, glutamate uptake, and expression of the astrocytic glutamate
      transporter 1 (GLT-1) and TREK-1 under different conditions. Under normal
      conditions, 3-30MUM AA showed no effect on astrocytic apoptosis or TREK-1
      expression, whereas glutamate uptake decreased significantly and its change
      paralleled the decreased expression of GLT-1. When astrocytes were subjected to
      4h of oxygen-glucose deprivation (OGD), 10MUM AA markedly alleviated OGD-induced
      cell death, recovering from 63.50+/-1.90% to 82.96+/-4.63% of the control value.
      AA also rescued the decreased glutamate uptake and increased mRNA, as well as
      protein levels of GLT-1 and TREK-1. Our results provide new evidence of a
      protective effect of AA on astrocytes under OGD conditions, suggesting that a low
      concentration of AA may protect against brain ischemic diseases.

PMID- 27865880
TI  - NOD2 mediates isoflurane preconditioning-induced protection of myocardial injury.
AB  - Anesthetic cardioprotection reduces myocardial infarct size following ischemia
      reperfusion injury. However, the underlying mechanisms that drive ischemia
      reperfusion injury in cardiomyocytes remain unclear. In this study, we report
      that isoflurane, a commonly used inhaled anesthetic, can protect cardiomyocytes
      from anoxia/reoxygenation injury by a nucleotide binding oligomerization domain
      containing 2 (NOD2)-dependent mechanism. The results showed that isoflurane
      increased cell viability, and decreased autophagosome generation in primary
      cardiomyocytes under anoxia/reoxygenation conditions. In addition, western blot
      revealed that isoflurane reduces the expression of NOD2. Overexpression of NOD2
      is accompanied by an increased expression of autophagy-related genes, decreased
      cell viability, and enhanced expression of phosphorylation p38-mitogen-activated
      protein kinase (p38MAPK), while NOD2 knockdown exerted the opposite effect.
      Following preconditioning with SB203580, a p38MAPK inhibitor, the inhibitory
      effect of isoflurane on cardiomyocytes autophagy was further enhanced, which
      suggests that p38MAPK is involved in the mechanism of cardioprotection provided
      by isoflurane. These findings reveal a novel mechanism underlying isoflurane
      afford protection of myocardial injury.

PMID- 27865881
TI  - Modulation of quadriceps corticospinal excitability by femoral nerve stimulation.
AB  - INTRODUCTION: We explored the conditioning effect of a percutaneous electrical
      pulse of the femoral nerve on cortical motor evoked responses in the rectus
      femoris muscle. METHODS: Corticospinal excitability of rectus femoris muscle was
      measured in sixteen healthy subjects, when a single transcranial magnetic pulse
      was preceded by an electrical femoral nerve stimulus, using twelve inter-stimulus
      intervals (from 10 to 275ms). We also evaluated the effects of the intensities of
      the transcranial magnetic and of the electrical pulses. RESULTS: Quadriceps motor
      evoked potentials were inhibited and facilitated when a single femoral nerve
      electrical stimulus was delivered at inter-stimulus intervals of 25ms and 150ms,
      respectively. The facilitation was reduced when low electrical intensity was
      used, while the inhibition decreased with high intensity transcranial magnetic
      pulse. CONCLUSION: Afferent inputs of a femoral stimulation modulate the
      responses elicited by transcranial magnetic pulses of the contralateral
      quadriceps motor cortex. This modulation indicates a sensorimotor integration of
      proximal lower limb muscles that may be mediated via different types of
      afferents. This could be of relevance for studies that explore the role of lower
      limb muscles in postural control and balance.

PMID- 27865882
TI  - Assessing and conceptualizing frontal EEG asymmetry: An updated primer on
      recording, processing, analyzing, and interpreting frontal alpha asymmetry.
AB  - Frontal electroencephalographic (EEG) alpha asymmetry is widely researched in
      studies of emotion, motivation, and psychopathology, yet it is a metric that has
      been quantified and analyzed using diverse procedures, and diversity in
      procedures muddles cross-study interpretation. The aim of this article is to
      provide an updated tutorial for EEG alpha asymmetry recording, processing,
      analysis, and interpretation, with an eye towards improving consistency of
      results across studies. First, a brief background in alpha asymmetry findings is
      provided. Then, some guidelines for recording, processing, and analyzing alpha
      asymmetry are presented with an emphasis on the creation of asymmetry scores,
      referencing choices, and artifact removal. Processing steps are explained in
      detail, and references to MATLAB-based toolboxes that are helpful for creating
      and investigating alpha asymmetry are noted. Then, conceptual challenges and
      interpretative issues are reviewed, including a discussion of alpha asymmetry as
      a mediator/moderator of emotion and psychopathology. Finally, the effects of two
      automated component-based artifact correction algorithms-MARA and ADJUST-on
      frontal alpha asymmetry are evaluated.

PMID- 27865877
TI  - Cough in the Athlete: CHEST Guideline and Expert Panel Report.
AB  - BACKGROUND: Cough is a common symptom experienced by athletes, particularly after
      exercise. We performed a systematic review to assess the following in this
      population: (1) the main causes of acute and recurrent cough, either exercise
      induced or not, (2) how cough is assessed, and (3) how cough is treated in this
      population. From the systematic review, suggestions for management were
      developed. METHODS: This review was performed according to the CHEST
      methodological guidelines and Grading of Recommendations Assessment, Development
      and Evaluation framework until April 2015. To be included, studies had to meet
      the following criteria: participants had to be athletes and adults and
      adolescents aged >= 12 years and had to complain of cough, regardless of its
      duration or relationship to exercise. The Expert Cough Panel based their
      suggestions on the data extracted from the review and final grading by consensus
      according to a Delphi process. RESULTS: Only 60 reports fulfilled the inclusion
      criteria, and the results of our analysis revealed only low-quality evidence on
      the causes of cough and how to assess and treat cough specifically in athletes.
      Although there was no formal evaluation of causes of cough in the athletic
      population, the most common causes reported were asthma, exercise-induced
      bronchoconstriction, respiratory tract infection (RTI), upper airway cough
      syndrome (UACS) (mostly from rhinitis), and environmental exposures. Cough was
      also reported to be related to exercise-induced vocal cord dysfunction among a
      variety of less common causes. Although gastroesophageal reflux disease (GERD) is
      frequent in athletes, we found no publication on cough and GERD in this
      population. Assessment of the causes of cough was performed mainly with
      bronchoprovocation tests and suspected disease-specific investigations. The
      evidence to guide treatment of cough in the athlete was weak or nonexistent,
      depending on the cause. As data on cough in athletes were hidden in a set of
      other data (respiratory symptoms), evidence tables were difficult to produce and
      were done only for cough treatment in athletes. CONCLUSIONS: The causes of cough
      in the athlete appear to differ slightly from those in the general population. It
      is often associated with environmental exposures related to the sport training
      environment and occurs predominantly following intense exercise. Clinical history
      and specific investigations should allow identification of the cause of cough as
      well as targeting of the treatment. Until management studies have been performed
      in the athlete, current guidelines that exist for the general population should
      be applied for the evaluation and treatment of cough in the athlete, taking into
      account specific training context and anti-doping regulations.

PMID- 27865883
TI  - Effects of salinity and copper co-exposure on copper bioaccumulation in marine
      rabbitfish Siganus oramin.
AB  - Marine fish living in estuaries and coastal areas commonly encounter the stress
      of both salinity and metal pollution. In this study, euryhaline rabbitfish
      Siganus oramin were exposed to 50 MUg L-1 waterborne Cu or 300 MUg g-1 dry wt
      dietary Cu at salinity 330/00, 250/00, 200/00, 100/00, and 50/00 for 30 days. The
      Cu accumulation in the liver (>20-fold increase) and intestine (>5-fold increase)
      significantly increased after either waterborne or dietary Cu acclimation.
      Moreover, Cu accumulation was further enhanced in the liver, intestine, plasma,
      and whole body of Cu-exposed fish at lower salinities. Similarly, the waterborne
      Cu uptake rate constants (kus) were stable in the control at different salinities
      but increased significantly (2-4 times higher) after waterborne Cu exposure.
      Conversely, the dietary Cu assimilation efficiencies (AEs) were significantly
      lower in the dietary Cu-exposed fish (3-5%) than in the control fish (8-16%) at
      different salinities, suggesting that dietary Cu acclimation partially alleviated
      the dietary Cu uptake from the high-Cu diet. The Cu efflux rate constants (kes)
      were comparable among all treatments as 0.060-0.071 d-1. The changes of Cu
      accumulation by different salinities and Cu exposure were well estimated by the
      biokinetic modeling. In summary, the present study indicates that rabbitfish can
      regulate Cu uptake and accumulation when acclimated to different salinities, but
      the Cu-exposed rabbitfish failed to prevent the elevation of Cu accumulation at
      low salinities. It therefore suggested that the concurrence of low salinity and
      high Cu exposure enhances the risks of Cu bioaccumulation and toxicity in
      rabbitfish.

PMID- 27865884
TI  - Photodegradation behaviour of sethoxydim and its comercial formulation Poast(r)
      under environmentally-relevant conditions in aqueous media. Study of
      photoproducts and their toxicity.
AB  - Photolysis is an important route for the abiotic degradation of many pesticides.
      However, the knowledge of the photolytic behaviour of these compounds and their
      commercial formulations under environmentally-relevant conditions are limited.
      The present study investigated the importance of photochemical processes on the
      persistence and fate of the herbicide sethoxydim and its commercial formulation
      Poast(r) in aqueous media. Moreover, the effect of important natural water
      substances (nitrate, calcium, and ferric ions) on the photolysis of the herbicide
      was also studied. The results showed that additives existing in the commercial
      formulation Poast(r) accelerated the rate of photolysis of sethoxydim by a factor
      of 3. On the contrary, the presence of nitrate and calcium ions had no effect on
      the photodegradation rate while ferric ions resulted in an important decrease in
      the half-life of sethoxydim possibly due to the formation of a complex. Different
      transformation products were identified in the course of sethoxydim irradiation
      and the effect of experimental conditions on their concentrations was
      investigated. Finally, Microtox(r) test revealed that aqueous solutions of
      sethoxydim photoproducts increased the toxicity to the bacteria Vibrio fischeri.

PMID- 27865886
TI  - Social regulation of ageing by young workers in the honey bee, Apis mellifera.
AB  - Organisms' lifespans are modulated by both genetic and environmental factors. The
      lifespan of eusocial insects is determined by features of the division of labor,
      which itself is influenced by social regulatory mechanisms. In the honey bee,
      Apis mellifera, the presence of brood and of old workers carrying out foraging
      tasks are important social drivers of ageing, but the influence of young adult
      workers is unknown, as it has not been experimentally teased apart from that of
      brood. In this study, we test the role of young workers in the ageing of their
      nestmates. We measured the impact of different social contexts characterized by
      the absence of brood and/or young adults on the lifespan of worker nestmates in
      field colonies. To acquire insight into the physiological processes occurring
      under these contexts, we analyzed the expression of genes known to affect honey
      bee ageing. The data showed that young workers significantly reduced the lifespan
      of nestmate workers, similar to the effect of brood on its own. Differential
      expression of vitellogenin, major royal jelly protein-1, and methylase
      transferase, but not methyl farneosate epoxidase genes suggests that young
      workers and brood influence ageing of adult nestmate workers via different
      physiological pathways. We identify young workers as an essential part of the
      social regulation of ageing in honey bee colonies.

PMID- 27865885
TI  - Perforations and angulations of 324 cervical medial cortical pedicle screws: a
      possible guide to avoid lateral perforations with use of pedicle screws in lower
      cervical spine.
AB  - BACKGROUND CONTEXT: More than half of the perforations reported with usage of
      cervical pedicle screws (CPS) are lateral perforations, endangering the vertebral
      artery. The medial cortical pedicle screw (MCPS) technique with partial drilling
      of the medial cortex shifts the trajectory of pedicle screws medially, decreasing
      the lateral perforations. PURPOSE: To evaluate the decrease in lateral
      perforations of CPS with use of MCPS technique, in relation to medial angulation.
      STUDY DESIGN/SETTING: Retrospective analysis and technical report of the MCPS
      technique and its safety. PATIENT SAMPLE: A total of 58 patients operated on
      between December 2011 and May 2015 with insertion of pedicle screws from C3 to C7
      were included in the study. OUTCOME MEASURES: Axial reconstructed computed
      tomography (CT) scan images of the inserted screws were evaluated for placement,
      perforations, and transverse plane angulations using the Surgimap software
      (Surgimap Spine 1.1.2.271 Intl. 2009 Nemaris LLC). The angulations of screws were
      analyzed by the type and level of placement through unpaired t test and analysis
      of variance test. METHODS: A total of 58 patients operated on between December
      2011 and May 2015 with insertion of pedicle screws from C3 to C7 were included in
      the study. There were 49 males and 9 females. Thirty-seven patients had cervical
      trauma, 17 had cervical spondylotic myelopathy, two had tumors, and two had
      ankylosing spondylitis. The average age was 49 years (range 18 to 80 years). The
      screws were inserted using the MCPS technique. All patients underwent
      postoperative CT scans with GE Optima CT540 16 slice CT scanner (GE Healthcare
      Chalfont St. Giles, Buckinghamshire, UK). Axial reconstructed images along the
      axis of the inserted screws were evaluated for placement and perforations.
      Further, all the screws were evaluated for transverse plane angulations using the
      Surgimap software. The angulations of screw were analyzed by the type and level
      of placement through unpaired t test and analysis of variance test. No funds were
      received by any of the authors for the purpose of the present study. RESULTS: A
      total of 324 screws were assessed with postoperative CT scans. Two hundred fifty
      six were found to be placed within the pedicle and 68 (20.98%) screws were found
      to have perforations. Forty screws (12.34%) had grade I medial perforations, 14
      screws (4.32%) had grade I lateral perforations, 10 screws (3.08%) had grade II
      medial perforations, and 4 screws (1.23%) had grade IIlateral perforations. The
      average angulation of the nonperforated screws (n=256) was 28.6 degrees  (43
      degrees -17 degrees ), that of laterally perforated screws was 20.33 degrees  (13
      degrees -24 degrees ), and that of the medially perforated screws was 34.94
      degrees  (45 degrees -20 degrees ). On statistical analysis with each series, the
      99% CI range for the in-screw angles was 27.91 degrees  to 29.34 degrees ; for
      the laterally perforated screw series, it was 18.42 degrees  to 22.23 degrees ;
      and that for the medially perforated screw series was 32.97 degrees  to 36.9
      degrees . CONCLUSIONS: The MCPS technique represents a shift in the concept of
      placement of CPS from the cancellous core to the medial cortex, avoiding screw
      deflection laterally by the thick proximal medial cortex. The present study shows
      that the lateral perforations can be consistently avoided, with a medial
      angulation of more than 27.91 degrees , which is the primary concern with the use
      of pedicle screws in lower cervical spine. Further, the MCPS technique reduces
      the lateral perforations at a lesser insertion angle, which is technically
      desirable.

PMID- 27865887
TI  - Effects of altered parental folate and one-carbon nutrient status on offspring
      growth and metabolism.

PMID- 27865888
TI  - A morphological and molecular study of Pseudocorynosoma Aznar, Perez Ponce de
      Leon and Raga 2006 (Acanthocephala: Polymorphidae) from Mexico with the
      description of a new species and the presence of cox 1 pseudogenes.
AB  - Pseudocorynosoma tepehuanesi n. sp., is described from the intestine of the ruddy
      duck Oxyura jamaicensis Gmelin, 1789 from single locality from northern Mexico.
      The new species is mainly distinguished morphologically from the other five
      described species of Pseudocorynosoma from the Americas (P. constrictum, type
      species, P. peposacae, P. anatarium, P. enrietti and P. iheringi) associated with
      waterfowl species by possessing a proboscis with 15 longitudinal rows with 7-8
      hooks each, a trunk expanded anteriorly and by having smaller lemniscus. Partial
      sequences of the mitochondrial gene cytochrome c oxidase subunit I (cox 1) and
      the large subunit (LSU) of ribosomal DNA including the domains D2+D3 were used
      independently to corroborate the morphological distinction between the new
      species and other two congeneric species (P. constrictum and P. anatarium) from
      North America. The genetic divergence estimated among the new species and the
      other two species ranged from 15 to 18% for cox 1 and from 3.2 to 4% for LSU. The
      cox 1 alignment shows 24 sequences from P. anatarium with abnormalities, which
      were defined as pseudogenes due the presence of insertions, deletions and
      premature stop codons. Maximum likelihood and Bayesian inference analyses with
      each data set showed that the acanthocephalans from ruddy duck represent an
      independent clade with strong bootstrap support and posterior probabilities. The
      phylogenetic tree inferred with cox 1 gene placed all the pseudogenes from P.
      anatarium in single clade suggesting that those genes arose after speciation
      process within genus Pseudocorynosoma. The morphological evidence, plus the
      monophyly in both phylogenetic analyses indicate that the acanthocephalans
      collected from intestine of the ruddy duck from northern Mexico represent a new
      species.

PMID- 27865889
TI  - Time to review treatment of isoniazid-resistant tuberculosis?

PMID- 27865891
TI  - Treatment of isoniazid-resistant tuberculosis with first-line drugs: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The results of some reports have suggested that treatment of
      isoniazid-resistant tuberculosis with the recommended regimens of first-line
      drugs might be suboptimal. We updated a previous systematic review of treatment
      outcomes associated with use of first-line drugs in patients with tuberculosis
      resistant to isoniazid but not rifampicin. METHODS: In this systematic review, we
      updated the results of a previous review to include randomised trials and cohort
      studies published in English, French, or Spanish to March 31, 2015, containing
      results of standardised treatment of patients with bacteriologically confirmed
      isoniazid-resistant tuberculosis (but not multidrug-resistant tuberculosis-ie,
      not resistant to rifampicin) in whom failure and relapse were bacteriologically
      confirmed. Results in patients with drug-sensitive tuberculosis included in the
      same studies were also analysed. We pooled treatment outcomes with random-effects
      meta-analysis. FINDINGS: We identified 19 cohort studies and 33 trials with 3744
      patients with isoniazid-resistant tuberculosis and 19 012 patients with drug
      sensitive disease. The pooled rates of failure or relapse, or both, and acquired
      drug resistance with all drug regimens were 15% (95% CI 12-18) and 3.6% (2-5),
      respectively, in patients with isoniazid-resistant tuberculosis and 4% (3-5) and
      0.6% (0.3-0.9) in those with drug-sensitive tuberculosis. Of patients with
      initial isoniazid-resistant tuberculosis with acquired drug resistance, 96% (93
      99) had acquired multidrug-resistant disease. Treatment of isoniazid-resistant
      tuberculosis with the WHO standard regimen for new patients resulted in treatment
      failure, relapse, and acquired multidrug resistance in 11% (6-17), 10% (5-15) and
      8% (3-13), respectively; treatment with the standard WHO regimen for previously
      treated patients resulted in treatment failure in 6% (2-10), relapse in 5% (2-8),
      and acquisition of multidrug resistance in 3% (0-6). For patients with drug
      sensitive disease treated with the standard retreatment regimen the rates were 1%
      (0-2), 5% (4-7), and 0.3% (0-0.6). INTERPRETATION: Treatment of isoniazid
      resistant tuberculosis with first-line drugs resulted in suboptimal outcomes,
      supporting the need for better regimens. Standardised empirical treatment of new
      cases could be contributing substantially to the multidrug-resistant epidemic,
      particularly in settings where the prevalence of isoniazid resistance is high.
      FUNDING: Canadian Institutes of Health Research.

PMID- 27865892
TI  - Dihydroartemisinin-piperaquine: if it works for control, can we use it for
      elimination?

PMID- 27865890
TI  - Safety, tolerability, and efficacy of repeated doses of dihydroartemisinin
      piperaquine for prevention and treatment of malaria: a systematic review and meta
      analysis.
AB  - BACKGROUND: Intermittent preventive treatment (IPT) for malaria is used in
      infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine
      (DP) is an effective, well tolerated artemisinin-based combination therapy. The
      long half-life of piperaquine makes it attractive for IPT. We conducted a
      systematic review and meta-analysis to establish the efficacy and safety of
      repeated treatment with DP. METHODS: Following PRISMA guidelines, we searched
      multiple databases on Sept 1, 2016, with the terms: "human" AND
      "dihydroartemisinin-piperaquine" OR "DHA-PPQ". Studies were eligible if they were
      randomised controlled trials (RCTs) or prospective cohort studies involving
      repeat exposures to standard 3-day courses of DP for either seasonal malaria
      chemoprevention, mass drug administration, or treatment of clinical malaria,
      conducted at any time and in any geographic location. Random-effects meta
      analysis was used to generate pooled incidence rate ratios and relative risks, or
      risk differences. FINDINGS: 11 studies were included: two repeat treatment
      studies (one in children younger than 5 years and one in pregnant women), and
      nine IPT trials (five in children younger than 5 years, one in schoolchildren,
      one in adults, two in pregnant women). Comparator interventions included placebo,
      artemether-lumefantrine, sulfadoxine-pyrimethamine (SP), SP+amodiaquine,
      SP+piperaquine, SP+chloroquine, and co-trimoxazole. Of 14 628 participants, 3935
      received multiple DP courses (2-18). Monthly IPT-DP was associated with an 84%
      reduction in the incidence of malaria parasitaemia measured by microscopy
      compared with placebo. Monthly IPT-DP was associated with fewer serious adverse
      events than placebo, daily co-trimoxazole, or monthly SP. Among 56 IPT-DP
      recipients (26 children, 30 pregnant women) with cardiac parameters, all QTc
      intervals were within normal limits, with no significant increase in QTc
      prolongation with increasing courses of DP. INTERPRETATION: Monthly DP appears
      well tolerated and effective for IPT. Additional data are needed in pregnancy and
      to further explore the cardiac safety with monthly dosing. FUNDING: Bill &
      Melinda Gates Foundation and NIH.

PMID- 27865894
TI  - Activation of peroxisome proliferator-activated receptor gamma in mammary
      epithelial cells upregulates the expression of tumor suppressor Cyld to mediate
      growth inhibition and anti-inflammatory effects.
AB  - Several studies have implicated the downregulation of the tumor suppressor Cyld
      expression in breast cancer development. However, the mechanisms that regulate
      Cyld expression in mammary epithelial cells are largely unknown. In order to
      investigate them, a bioinformatic analysis of the promoter region of Cyld was
      performed and identified putative nuclear hormone receptor response elements that
      included peroxisome proliferator-activated receptor gamma (PPAR-gamma)-responsive
      elements. In the present study, we showed that upon activation of the nuclear
      hormone receptor PPAR-gamma by the agonist troglitazone (TZD), there was a
      significant increase in Cyld mRNA in human mammary epithelial cell lines. The
      effect of TZD could be attributed to the transactivation of the Cyld promoter as
      indicated by the upregulation of a luciferase reporter that was driven by the 
      1995 to +95 region of the human Cyld gene. Furthermore, the upregulation of Cyld
      expression by TZD was dependent on PPAR-gamma since downregulation of PPAR-gamma
      expression by RNAi compromised the induction of Cyld expression by TZD. CYLD
      induction mediated, at least in part, the TZD-mediated downregulation of tumor
      necrosis factor alpha (TNFalpha)-induced interleukin 8 (IL-8). In addition,
      downregulation of CYLD compromised the cytotoxic effects of TZD in immortalized
      mammary epithelial cells. Our results demonstrated that PPAR-gamma is a novel
      regulator of Cyld transcription and identified CYLD as a mediator of the PPAR
      gamma-dependent anti-inflammatory and anti-proliferative activity in mammary
      epithelial cells, which underscores its potential to be used as a target for the
      development of breast cancer therapeutic approaches.

PMID- 27865896
TI  - Reduced cytotoxicity in PCB-exposed Chinese Hamster Ovary (CHO) cells pretreated
      with vitamin E.
AB  - The aim of this study was to evaluate protective effects of vitamin E (50 -150
      MUM) in ovary cells upon cytotoxic effects induced by two structurally distinct
      PCB congeners - planar "dioxin-like" PCB 77 and non-planar di-ortho-substituted
      PCB 153 with an emphasis on identifying differences in the mechanism of vitamin E
      action depending on the structure of congeners. Application of three bioassays
      confirmed that PCBs decrease ovarian cell proliferation with slightly profound
      effects of PCB 77. PCB - induced ROS production and lipid peroxidation were
      significant for both congeners with also more noticeable effect for PCB 77.
      Vitamin E pre-incubation has improved viability of cells, reduced ROS formation
      and lipid peroxidation induced by PCBs' treatment. Preincubation with vitamin E
      was more effective when cells where treated with non-planar PCB 153. Altogether,
      vitamin E action was protective, congener specific and more effective when ovary
      cells were exposed to ortho-substituted PCB congener.

PMID- 27865895
TI  - Intensive care unit-acquired pneumonia due to Pseudomonas aeruginosa with and
      without multidrug resistance.
AB  - OBJECTIVE: Pseudomonas aeruginosa often presents multi-drug resistance (MDR) in
      intensive care unit (ICU)-acquired pneumonia (ICUAP), possibly resulting in
      inappropriate empiric treatment and worse outcomes. We aimed to identify patients
      with ICUAP at risk for these pathogens in order to improve treatment selection
      and outcomes. METHODS: We prospectively assessed 222 consecutive immunocompetent
      ICUAP patients confirmed microbiologically. We determined the characteristics,
      risk factors, systemic inflammatory response and outcomes of P. aeruginosa
      pneumonia (Pa-ICUAP), compared to other aetiologies. We also compared patients
      with MDR vs. non-MDR Pa-ICUAP. RESULTS: Pseudomonas aeruginosa was the most
      frequent aetiology (64, 29%); 22 (34%) cases had MDR. Independent predictors for
      Pa-ICUAP were prior airway colonization by P. aeruginosa, previous antibiotic
      treatment, solid cancer and shock; alcohol abuse and pleural effusion were
      independently associated to lower risk for Pa-ICUAP. Chronic liver disease
      independently predicted MDR among Pa-ICUAP. The inflammatory biomarkers were
      similar between all groups. Patients with Pa-ICUAP had lower unadjusted 90-day
      survival (p = 0.049). However, the 90-day survival adjusted for confounding
      factors using a propensity score did not differ between all groups. CONCLUSION:
      Pseudomonas aeruginosa remains the most frequent aetiology of ICUAP, with high
      prevalence of MDR. These risk factors should be taken into account to avoid
      inappropriate empiric antibiotics for Pa-ICUAP. Pseudomonas aeruginosa,
      regardless multidrug resistance, was not associated with different propensity
      adjusted survival.

PMID- 27865893
TI  - Sex and genetic differences in the effects of acute diesel exhaust exposure on
      inflammation and oxidative stress in mouse brain.
AB  - In addition to increased morbidity and mortality caused by respiratory and
      cardiovascular diseases, air pollution may also contribute to central nervous
      system (CNS) diseases. Traffic-related air pollution is a major contributor to
      global air pollution, and diesel exhaust (DE) is its most important component. DE
      contains more than 40 toxic air pollutants and is a major constituent of ambient
      particulate matter (PM), particularly of ultrafine-PM. Limited information
      suggests that exposure to DE may cause oxidative stress and neuroinflammation in
      the CNS. We hypothesized that males may be more susceptible than females to DE
      neurotoxicity, because of a lower level of expression of paraoxonase 2 (PON2), an
      intracellular anti-oxidant and anti-inflammatory enzyme. Acute exposure of
      C57BL/6 mice to DE (250-300MUg/m3 for 6h) caused significant increases in lipid
      peroxidation and of pro-inflammatory cytokines (IL-1alpha, IL-1beta, IL-3, IL-6,
      TNF-alpha) in various brain regions (particularly olfactory bulb and
      hippocampus). In a number of cases the observed effects were more pronounced in
      male than in female mice. DE exposure also caused microglia activation, as
      measured by increased Iba1 (ionized calcium-binding adapter molecule 1)
      expression, and of TSPO (translocator protein) binding. Mice heterozygotes for
      the modifier subunit of glutamate cysteine ligase (the limiting enzyme in
      glutathione biosynthesis; Gclm+/- mice) appeared to be significantly more
      susceptible to DE-induced neuroinflammation than wild type mice. These findings
      indicate that acute exposure to DE causes neuroinflammation and oxidative stress
      in brain, and suggest that sex and genetic background may play important roles in
      modulating susceptibility to DE neurotoxicity.

PMID- 27865898
TI  - Keeping time in the chest.

PMID- 27865897
TI  - Enigmas in tumor resistance to kinase inhibitors and calculation of the drug
      resistance index for cancer (DRIC).
AB  - Darwinian selection is also applicable when antibiotics, the immune system or
      other host factors shape the repertoire of microorganisms, and similarly, clonal
      selection is the hallmark of tumor evolution. The ongoing revolution in new anti
      cancer treatment modalities, combined with an unprecedented precision in
      characterizing malignant clones at the level below one percent, profoundly
      improves the understanding of repertoire-tuning mechanisms. There is no
      fundamental difference between selection of the tumor cells in the presence, or
      absence, of therapy. However, under treatment the influence of a single agent can
      be measured, simplifying the analysis. Because of their beneficial and selective
      therapeutic effect, the focus in this review is set on protein kinase inhibitors
      (PKIs), predominantly tyrosine kinase inhibitors (TKIs). This is one of the most
      rapidly growing families of novel cancer medicines. In order to limit the number
      of drugs, the following representative target kinases are included: ALK, BCR-ABL,
      BRAF, BTK, and EGFR. A key therapeutic challenge is how to reduce tumor growth
      after treatment, since this is rate-limiting for the generation and expansion of
      more malignant escape mutants. Thus, upon efficient treatment, tumor cell loss
      often enables a profoundly increased growth rate among resistant cells.
      Strategies to reduce this risk, such as concomitant, competitive outgrowth of non
      transformed cells, are described. Seven parameters: 1. Drug type, 2. tumor type,
      3. presence of metastases or phenotypic change, 4. tumor cell number, 5. net
      growth rate (proliferation minus cell death), 6. inherited genetic- and 7.
      epigenetic- variations are crucial for drug responses. It is envisaged that it
      might become possible to calculate a clinically relevant Drug Resistance Index
      for Cancer (DRIC) for each patient.

PMID- 27865899
TI  - A systematic review finds limited data on measurement properties of instruments
      measuring outcomes in adult intensive care unit survivors.
AB  - BACKGROUND AND OBJECTIVE: There is a growing number of studies evaluating the
      physical, cognitive, mental health, and health-related quality of life (HRQOL)
      outcomes of adults surviving critical illness. However, there is little consensus
      on the most appropriate instruments to measure these outcomes. To inform the
      development of such consensus, we conducted a systematic review of the
      performance characteristics of instruments measuring physical, cognitive, mental
      health, and HRQOL outcomes in adult intensive care unit (ICU) survivors. METHODS:
      We searched PubMed, Embase, PsycInfo, Cumulative Index of Nursing and Allied
      Health Literature, and The Cochrane Library in March 2015. We also conducted
      manual searches of reference lists of eligible studies and relevant review
      articles. Two people independently selected studies, completed data abstraction,
      and assessed the quality of eligible studies using the COnsensus-based Standards
      for the selection of health Measurement Instruments (COSMIN) initiative
      checklist. RESULTS: We identified 20 studies which explicitly evaluated
      measurement properties for 21 different instruments assessing outcomes in ICU
      survivors. Eleven of the instruments assessed quality of life, with few
      instruments assessing other domains. Of the nine measurement properties evaluated
      on the COSMIN checklist, six were assessed in <10% of the evaluations. Overall
      quality of eligible studies was generally poor to fair based on the COSMIN
      checklist. CONCLUSIONS: Although an increasing number of studies measure
      physical, cognitive, mental health, and HRQOL outcomes in adult ICU survivors,
      data on the measurement properties of such instruments are sparse and generally
      of poor to fair quality. Empirical analyses evaluating the performance of
      instruments in adult ICU survivors are needed to advance research in this field.

PMID- 27865901
TI  - Published randomized trials performed in Sub-Saharan Africa focus on high-burden
      diseases but are frequently funded and led by high-income countries.
AB  - BACKGROUND AND OBJECTIVE: In light of funding constraints in Sub-Saharan Africa
      (SSA), the value of research performed there must be increased. The objective of
      this study was to describe the epidemiology of published randomized controlled
      trials (RCTs) performed in SSA. METHODS: We searched PubMed, the Cochrane
      library, and African Index Medicus to identify reports of all RCTs performed in
      SSA and published between January 1, 2014 and March 31, 2015. We systematically
      recorded the country of the affiliation of the corresponding author and the
      funding source. The overall burden of disease was assessed by 2013 disability
      adjusted life years (both sexes, all ages) in percentages for two locations: SSA
      and high-income countries (HICs). RESULTS: Only 12 of 121 RCTs were conducted in
      both Sub-Saharan Africa and another region, with 109 of 121 RCTs (90%) having
      trial centers exclusively located in SSA. The corresponding author's only
      affiliation was in SSA for 44/109 trials (40%) and was institutions in HICs for
      almost half of the trials. The funding source was nonprofit for 77/109 trials
      (70%) and was from HICs for 81% (n = 63/77). Overall, most RCTs targeted diseases
      with a high burden in SSA; 46% of the trials targeted the five diseases with the
      highest burden in SSA, mainly malaria (n = 25), HIV/AIDS (n = 24), lower
      respiratory tract infection (n = 2), diarrheal diseases (n = 3), and preterm
      birth complications (n = 2). Nevertheless, among the 25 diseases or health
      related conditions with the highest burden in SSA, 9 (36%) were not assessed in
      any RCT. CONCLUSIONS: Published RCTs performed in SSA were mainly funded and led
      by HIC institutions, although investigations concerned diseases highly prevalent
      in SSA.

PMID- 27865900
TI  - Potentially unnecessary and wasteful clinical trial research detected in
      cumulative meta-epidemiological and trial sequential analysis.
AB  - OBJECTIVE: The objective was to estimate the presence and extent to which
      potentially unnecessary and therefore maybe wasteful clinical trials regarding
      relevant interventions and outcomes in major clinical areas had been conducted.
      STUDY DESIGN AND SETTING: From current Cochrane collaboration systematic reviews
      in major medical fields (e.g., cardiovascular disease, cancer, psychiatry), 13
      different comparisons were sampled. A cumulative meta-analysis was conducted for
      each and trial sequential analysis applied to determine when in the course of
      evidence accrual evidence was found sufficient to reach a reliable conclusion.
      Trials published afterward were considered potentially unnecessary. Sensitivity
      analysis is performed, for example, to determine if findings could be explained
      by a delayed perception of published findings when planning new trials. RESULTS:
      In 8/13 cases, potentially unnecessary research was detected to an extent of
      between 12% and 89% of all participants in trials that might not have been
      needed. In three of these cases with high proportions (69-89%) of potentially
      unnecessary research, this finding was found basically unchanged in sensitivity
      analysis, when only trials published 3 or 5 years after sufficient evidence had
      already been published were considered potentially wasteful. CONCLUSIONS: The
      reasonableness of claims to relevance of additional trials needs to be much more
      carefully evaluated in the future. Cumulative, information size bases analysis
      might be included in systematic reviews. Research policies to prevent unnecessary
      research from being done need to be developed.

PMID- 27865902
TI  - The regression discontinuity design showed to be a valid alternative to a
      randomized controlled trial for estimating treatment effects.
AB  - OBJECTIVES: To compare treatment effect estimates obtained from a regression
      discontinuity (RD) design with results from an actual randomized controlled trial
      (RCT). STUDY DESIGN AND SETTING: Data from an RCT (EVIDENT), which studied the
      effect of an Internet intervention on depressive symptoms measured with the
      Patient Health Questionnaire (PHQ-9), were used to perform an RD analysis, in
      which treatment allocation was determined by a cutoff value at baseline (PHQ-9 =
      10). A linear regression model was fitted to the data, selecting participants
      above the cutoff who had received the intervention (n = 317) and control
      participants below the cutoff (n = 187). Outcome was PHQ-9 sum score 12 weeks
      after baseline. Robustness of the effect estimate was studied; the estimate was
      compared with the RCT treatment effect. RESULTS: The final regression model
      showed a regression coefficient of -2.29 [95% confidence interval (CI): -3.72 to 
      .85] compared with a treatment effect found in the RCT of -1.57 (95% CI: -2.07 to
      -1.07). CONCLUSION: Although the estimates obtained from two designs are not
      equal, their confidence intervals overlap, suggesting that an RD design can be a
      valid alternative for RCTs. This finding is particularly important for situations
      where an RCT may not be feasible or ethical as is often the case in clinical
      research settings.

PMID- 27865905
TI  - Editorial Comment.

PMID- 27865903
TI  - On-command controlled drug release by diels-Alder reaction using Bi-magnetic
      core/shell nano-carriers.
AB  - A novel bi-functional thermo-responsive system, consisting of core/shell bi
      magnetic nanoparticles with furan surface functionality, is bonded with N-(2
      Carboxyethyl)maleimide through Diels-Alder reaction. The chemotherapeutics
      doxorubicin is attached onto the surface, with a high loading efficiency of 92%.
      This system with high responsiveness to a high frequency external alternating
      magnetic field shows a very good therapeutic efficiency in hyperthermia and drug
      release at relatively low temperatures (50 degrees C). Polyhedron-shaped bi
      magnetic nanoparticles (Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4) exhibit a significant
      increase of the specific energy absorption rate up to 455W/g compared with the
      core nanoparticles (200W/g). Real-time florescence spectroscopy studies
      demonstrate rapid release of doxorubicin up to 50% in 5min and up to 92% after
      15min upon exposure to high frequency external alternating magnetic field. The
      stability is evaluated for 8 weeks in phosphate buffer saline with a doxorubicin
      payload of 85%. In vitro studies using standard MTT cell assays with HeLa and Hep
      G2 lines prove an excellent biocompatibility with about 90% of cell viability
      after 24h of treatment within the highest concentration of functionalized
      magnetic nanoparticles (200MUg/mL). The results indicate a controlled drug
      release mediated by thermo-responsive switching under applied alternating
      magnetic field.

PMID- 27865906
TI  - Editorial Comment.

PMID- 27865904
TI  - Surprises of electron microscopic imaging of proteins and polymers covering gold
      nanoparticles layer by layer.
AB  - Gold nanoparticles (GNPs) are used in complicated nanoconstructions, and their
      preparation implies careful analysis of the intermediate and resulting products,
      including visualisation of the NPs. Visualisation of protein and/or organic
      polymer covers on GNPs using electron microscopy (EM) was a goal of this study.
      We covered GNPs with human serum albumin or PEG, and then added a second layer of
      branched or linear polyethyleneimine. EM studies were supplemented with dynamic
      light scattering, spectrophotometry and gel electrophoresis, which confirmed the
      presence and integrity of a cover on GNPs in mixtures with uranylacetate (UA) or
      phosphotungstic acid (PTA). Covered GNPs were contrasted 'on a drop' or in
      suspension with UA (pH 4.5) or PTA (pH 0.5, 3.0, 5.0 and 7.0), and studied by
      transmission EM. A cover on GNPs becomes visible as the result of direct
      interaction of UA or PTA with the components of a layer. The same NPs could look
      'naked' or demonstrate a distinct cover of average electron density. The most
      distinct images of the layers were obtained using PTA at pH 0.5. Thus,
      visualisation of protein and/or polymeric layers covering the GNPs by EM depends
      on the type of contrasting reagent and contrasting conditions, but does not
      depend on surface charge of the NPs and the chemical nature of a cover.

PMID- 27865907
TI  - Differential regulation of glial reactions in the central facial tract and the
      facial nucleus after facial neurorrhaphy.
AB  - We previously reported that perineuronal astrocytic and microglial reactions are
      drastically upregulated in the facial nucleus after facial axotomy at the brain
      stem surface or the stylomastoid foramen. Furthermore, periaxonal astrocytic and
      microglial reactions develop retrogradely in the central facial tract which
      contains proximal facial axons in the brain stem. Because reconnection of
      interrupted peripheral nerve by microsurgical suture is a common clinical
      practice, the aim of this study was to investigate the spatiotemporal patterns of
      glial reactions in the central facial tract and the facial nucleus after facial
      neurorrhaphy. Here, we show immunofluorescent and immunohistochemical evidence
      that facial neurorrhaphy at the stylomastoid foramen largely prevented axotomy
      induced astrocytic and microglial activation in the central facial tract. In
      contrast, glial reactions in the facial nucleus were still highly elevated after
      facial neurorrhaphy. Microglial and astrocytic processes were observed to
      ensheath the facial motoneurons in the facial nucleus. Nevertheless, the
      transformation of ramified to amoeboid shape of microglia, occurring at 10 weeks
      after facial axotomy, was not seen after neurorrhaphy. We further examined the
      effect of N-nitro-l-arginine methyl ester (L-NAME), an inhibitor of nitric oxide
      synthase (NOS), on glial reactions after neurorrhaphy. Western blot analyses
      demonstrate that inhibition of nitric oxide (NO) production significantly reduced
      microglial but not astrocytic reaction in the facial nucleus after neurorrhaphy.
      Taken together, these results indicate that in contrast to the intense glial
      reactions in both the central facial tract and the facial nucleus after facial
      axotomy, glial reactions are differentially regulated in these two compartments
      after facial neurorrhaphy. NO is involved in the activation of microglia in the
      facial nucleus after facial neurorrhaphy.

PMID- 27865908
TI  - Oleic acid promotes the expression of neural markers in differentiated human
      endometrial stem cells.
AB  - Variety of neurodegenerative diseases in humans are caused by loss of cells along
      with loss of function and disability. Cell replacement therapy is a potential
      strategy to cure neurodegenerative diseases. Mesenchymal stem cells are
      pluripotent non-hematopoietic cells that can be isolated from numerous tissues.
      Human endometrial-derived stem cell (hEnSC) are the abundant and easy available
      source with no immunological response, for cell replacement therapy. In the
      nervous system, where fatty acids are found in huge amounts, they participate in
      its development and maintenance throughout life. Oleic acid is a kind of the
      saturated fatty acids which plays crucial role in brain development. Oleic acid
      released by astrocytes is used by neurons for the synthesis of phospholipids and
      is specifically incorporated into growth cones. Human endometrial-derived stem
      cells in the third passage were divided into 3 groups including: control, sham
      (cultured in full differentiation medium without oleic acid) and experimental
      group (cultured in full differentiation medium with oleic acid) to differentiate
      over a 18-day period. Data from Real-Time PCR showed that mRNA levels of NF and
      beta-TUBULIN were increased significantly (p<0.05) in oleic acid treated cells in
      comparison to control and sham groups. Immunocytochemistry analysis of Chat and
      NF expression also showed the same results. The present study clearly
      demonstrates that oleic acid promotes neural differentiation of hEnSC through
      regulation of gene expression.

PMID- 27865909
TI  - Experimental evidence concerning the significant information depth of electron
      backscatter diffraction (EBSD).
AB  - Experiments concerning the information depth of electron backscatter diffraction
      (EBSD) are performed on samples featuring an amorphous wedge on a crystalline
      substrate and a crystalline wedge on an amorphous substrate. The effects of the
      acceleration voltage and exemplary software settings on the ability to measure
      through an amorphous layer are presented. Changes in the EBSD-signal could be
      detected through a ~142nm thick layer of amorphous Si while orientation
      measurements could be performed through a ~116nm thick layer when using a voltage
      of 30kV. The complexity of the information depth significant to a given EBSD
      pattern and the multiple parameters influencing it are discussed. It is suggested
      that a "core information depth" is significant to high quality patterns while a
      larger "maximum information depth" becomes relevant when the pattern quality
      decreases or the sample is inhomogeneous within the information volume, i.e. in
      the form of partially crystalline materials or crystal layers in the nm scale.

PMID- 27865910
TI  - Multi-target-directed therapeutic potential of 7-methoxytacrine-adamantylamine
      heterodimers in the Alzheimer's disease treatment.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder and
      currently there is no efficient treatment. The classic drug-design strategy based
      on the "one-molecule-one-target" paradigm was found to be ineffective in the case
      of multifactorial diseases like AD. A novel multi-target-directed ligand strategy
      based on the assumption that a single compound consisting of two or more distinct
      pharmacophores is able to hit multiple targets has been proposed as promising.
      Herein, we investigated 7-methoxytacrine - memantine heterodimers developed with
      respect to the multi-target-directed ligand theory. The spectroscopic,
      microscopic and cell culture methods were used for systematic investigation of
      the interference of the heterodimers with beta-secretase (BACE1) activity, Abeta
      peptide amyloid fibrillization (amyloid theory) and interaction with M1 subtype
      of muscarinic (mAChRs), nicotinic (nAChRs) acetylcholine receptors (cholinergic
      theory) and N-methyl-d-aspartate receptors (NMDA) (glutamatergic theory). The
      drug-like properties of selected compounds have been evaluated from the point of
      view of blood-brain barrier penetration and cell proliferation. We have confirmed
      the multipotent effect of novel series of compounds. They inhibited effectively
      Abeta peptide amyloid fibrillization and affected the BACE1 activity. Moreover,
      they have AChE inhibitory potency but they could not potentiate cholinergic
      transmission via direct interaction with cholinergic receptors. All compounds
      were reported to act as an antagonist of both M1 muscarinic and muscle-type
      nicotinic receptors. We have found that 7-methoxytacrine - memantine heterodimers
      are able to hit multiple targets associated with Alzheimer's disease and thus,
      have a potential clinical impact for slowing or blocking the neurodegenerative
      process related to this disease.

PMID- 27865911
TI  - Allogeneic Hematopoietic Cell Transplantation Is Safe and Effective Treatment in
      Patients with Myelodysplastic Syndromes Seventy Years and Older.

PMID- 27865912
TI  - The Value of Minimal Residual Disease (and Diamonds).

PMID- 27865913
TI  - TiO2/UV based photocatalytic pretreatment of wheat straw for biogas production.
AB  - The present study deals with the application of an advanced oxidation process
      combining UV irradiation in the presence of the photocatalyst titanium dioxide
      (TiO2), as an effective pretreatment method of wheat straw as means for
      increasing its biodegradability for increased biogas production by anaerobic
      digestion (AD). Especially attention was paid in oxidation of the lignin in
      straw, besides release the sugars from the lignocellulosic structure of straw.
      Specifically, four different TiO2 concentrations (0.0, 0.5, 1.0, 1.5, and 2.0%
      (w/w) TiO2) were tested at three different irradiation times (0, 1, 2, and 3 h).
      Products of lignin-fraction oxidation, namely, vanillic acid, ferullic acid and
      acetic acid were quantified for each set of pretreatment conditions.
      Subsequently, biochemical methane potentials (BMPs) assays were conducted under
      thermophilic conditions from differentially pretreated samples and the
      pretreatment with the best performance was further tested in continuous mode
      operation. From BMP assays, 1.5% (w/w) TiO2/straw at 3 h of UV light exposure
      pretreatment resulted in 37% (p < 0.05) increase in methane yield and 25% in
      CSTRs. It was concluded that the presence of TiO2 and the products of lignin
      oxidation did not inhibit the AD process. Finally, a simplified energy assessment
      showed that all pretreatment conditions become feasible when amounts of substrate
      to be treated are greater than the threshold value of 1.15 g.

PMID- 27865914
TI  - Analgesia following adenotonsillar surgery in children: is Oramorph required in
      addition to paracetamol and ibuprofen?
AB  - BACKGROUND: Recent advice against codeine use in children prompted our unit to
      prescribe Oramorph as required, in addition to regular paracetamol and ibuprofen,
      as post-(adeno)tonsillectomy analgesia. This study investigated whether Oramorph
      was in fact required. METHODS: Following (adeno)tonsillectomy, parents were
      telephoned and asked whether they used Oramorph. RESULTS: Of 56 children studied,
      41 (73.2%) were given Oramorph. In the 15 (26.8%) that were not, this was because
      parents felt it was not required in 14 children, and in 1 case, it was due to
      worries about side effects. Overall, 14 carers (25.0%) expressed concerns about
      Oramorph use, mostly over possible side effects. CONCLUSION: When regular
      paracetamol and ibuprofen are used post-(adeno)tonsillectomy, nearly three
      quarters of children require Oramorph as well. Prescribing Oramorph as required,
      in addition to regular paracetamol and ibuprofen, is appropriate following
      adenotonsillar surgery.

PMID- 27865915
TI  - Functional promoter polymorphisms direct the expression of cystathionine gamma
      lyase gene in mouse models of essential hypertension.
AB  - Despite the well-known role of cystathionine gamma-lyase (Cth) in cardiovascular
      pathophysiology, transcriptional regulation of Cth remains incompletely
      understood. Sequencing of the Cth promoter region in mouse models of
      genetic/essential hypertension (viz. Blood Pressure High [BPH], Blood Pressure
      Low [BPL] and Blood Pressure Normal [BPN] mice) identified several genetic
      variations. Transient transfections of BPH/BPL-Cth promoter-reporter plasmids
      into various cell types revealed higher promoter activity of BPL-Cth than that of
      BPH-Cth. Corroboratively, endogenous Cth mRNA levels in kidney and liver tissues
      were also elevated in BPL mice. Computational analysis of the polymorphic Cth
      promoter region predicted differential binding affinity of c-Rel, HOXA3 and IRF1
      with BPL/BPH-Cth promoter domains. Over-expression of c-Rel/HOXA3/IRF1 modulated
      BPL/BPH-Cth promoter activities in a consistent manner. Gel shift assays using
      BPH/BPL-Cth-promoter oligonucleotides with/without binding sites for c
      Rel/HOXA3/IRF1 displayed formation of specific complexes with c-Rel/HOXA3/IRF1;
      addition of antibodies to reaction mixtures resulted in supershifts/inhibition of
      Cth promoter-transcription factor complexes. Furthermore, chromatin
      immunoprecipitation (ChIP) assays proved differential binding of c-Rel, HOXA3 and
      IRF1 with the polymorphic promoter region of BPL/BPH-Cth. Tumor necrosis factor
      alpha (TNF-alpha) reduced the activities of BPL/BPH-Cth promoters to different
      extents that were further declined by ectopic expression of IRF1; on the other
      hand, siRNA-mediated down-regulation of IRF1 rescued the TNF-alpha-mediated
      suppression of the BPL/BPH-Cth promoter activities. In corroboration, ChIP
      analysis revealed enhanced binding of IRF1 with BPH/BPL-Cth promoter following
      TNF-alpha treatment. BPL/BPH-Cth promoter activity was diminished upon exposure
      of hepatocytes and cardiomyoblasts to ischemia-like pathological condition due to
      reduced binding of c-Rel with BPL/BPH-Cth-promoter. Taken together, this study
      reveals the molecular basis for the differential expression of Cth in mouse
      models of essential hypertension under basal and pathophysiological conditions.

PMID- 27865917
TI  - The co-expression of GluN2B subunits of the NMDA receptors and glucocorticoid
      receptors after chronic restraint stress in low and high anxiety rats.
AB  - The aim of this study was to assess the mechanisms underlying behavioural
      differences between high- (HR) and low- (LR) anxiety rats, selected according to
      their behaviour in the contextual fear test (i.e., the duration of the freezing
      response was used as a discriminating variable), after a chronic restraint
      procedure (21days, 3h daily). We analysed the expression of the GluN2B subunits
      of the NMDA and glucocorticoid receptors (GRs) in selected brain structures
      (immunofluorescence). Following chronic restraint stress in the HR rats, we
      observed a decrease in the expression of the GRs and GluN2B subunits of the NMDA
      receptor in the prefrontal cortical areas and the hippocampus compared to the HR
      control and the LR-restraint groups. These effects coincided with an increase in
      passive depressive-like behaviour in the Porsolt test of the HR rats. Moreover,
      in the hippocampus, the HR-restraint animals demonstrated decreased glutamate
      levels and a decreased glutamate/glutamine ratio compared to the LR-restraint
      rats. Furthermore, the HR-restraint group had increased GRs/GluN2B subunits
      colocalisation in the basolateral amygdala (BLA) compared to the HR-control and
      the LR-restraint rats. The present results suggest that in HR rats exposed to
      chronic restraint stress, the hippocampal and cortical glutamatergic system
      components are changed. These effects could have a negative influence on the
      feedback mechanisms regulating the hypothalamic-pituitary-adrenal axis as well as
      on the behavioural processes expressed as depressive-like symptoms.

PMID- 27865916
TI  - Neutrophil gelatinase-associated lipocalin and microglial activity are associated
      with distinct postoperative behavioral changes in rats.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) has recently gained interest as
      a marker for neuroinflammation and associated behavioral dysfunction. We aimed to
      explore the link between NGAL and behavior in a rat model of postoperative
      cognitive dysfunction (POCD). Material collected in two previous studies on POCD
      was analyzed and associated with outcomes for exploratory behavior and spatial
      learning. Plasma and hippocampal NGAL and microglial activity were analyzed.
      Pearson's correlations and backward linear regression were performed to study the
      associations between behavioral parameters, NGAL concentrations, and microglial
      activity. Plasma and hippocampal NGAL were increased following surgery. Plasma
      NGAL was associated with impaired spatial learning only, microglial activity was
      associated with exploratory behavior only, while hippocampal NGAL was associated
      with both behavioral aspects. Spatial learning was best predicted by a model
      containing plasma NGAL concentrations and hippocampal microglial activity. NGAL
      may serve as a sensitive marker in connecting the peripheral inflammatory state
      to POCD, while postoperative changes in exploratory behavior are better reflected
      by hippocampal neuroinflammation. These findings warrant further exploration in
      the role of NGAL in development of postoperative behavioral deficits.

PMID- 27865918
TI  - Enhanced cued fear memory following post-training whole body irradiation of 3
      month-old mice.
AB  - Typically, in studies designed to assess effects of irradiation on cognitive
      performance the animals are trained and tested for cognitive function following
      irradiation. Little is known about post-training effects of irradiation on
      cognitive performance. In the current study, 3-month-old male mice were
      irradiated with X-rays 24h following training in a fear conditioning paradigm and
      cognitively tested starting two weeks later. Average motion during the extinction
      trials, measures of anxiety in the elevated zero maze, and body weight changes
      over the course of the study were assessed as well. Exposure to whole body
      irradiation 24h following training in a fear conditioning resulted in greater
      freezing levels 2 weeks after training. In addition, motion during both
      contextual and cued extinction trials was lower in irradiated than sham
      irradiated mice. In mice trained for cued fear conditioning, activity levels in
      the elevated zero maze 12days after sham-irradiation or irradiation were also
      lower in irradiated than sham-irradiated mice. Finally, the trajectory of body
      weight changes was affected by irradiation, with lower body weights in irradiated
      than sham-irradiated mice, with the most profound effect 7days after training.
      These effects were associated with reduced c-Myc protein levels in the amygdala
      of the irradiated mice. These data indicate that whole body X ray irradiation of
      mice at 3 months of age causes persistent alterations in the fear response and
      activity levels in a novel environment, while the effects on body weight seem
      more transient.

PMID- 27865921
TI  - Community detection in weighted brain connectivity networks beyond the resolution
      limit.
AB  - Graph theory provides a powerful framework to investigate brain functional
      connectivity networks and their modular organization. However, most graph-based
      methods suffer from a fundamental resolution limit that may have affected
      previous studies and prevented detection of modules, or "communities", that are
      smaller than a specific scale. Surprise, a resolution-limit-free function rooted
      in discrete probability theory, has been recently introduced and applied to brain
      networks, revealing a wide size-distribution of functional modules (Nicolini and
      Bifone, 2016), in contrast with many previous reports. However, the use of
      Surprise is limited to binary networks, while brain networks are intrinsically
      weighted, reflecting a continuous distribution of connectivity strengths between
      different brain regions. Here, we propose Asymptotical Surprise, a continuous
      version of Surprise, for the study of weighted brain connectivity networks, and
      validate this approach in synthetic networks endowed with a ground-truth modular
      structure. We compare Asymptotical Surprise with leading community detection
      methods currently in use and show its superior sensitivity in the detection of
      small modules even in the presence of noise and intersubject variability such as
      those observed in fMRI data. We apply our novel approach to functional
      connectivity networks from resting state fMRI experiments, and demonstrate a
      heterogeneous modular organization, with a wide distribution of clusters spanning
      multiple scales. Finally, we discuss the implications of these findings for the
      identification of connector hubs, the brain regions responsible for the
      integration of the different network elements, showing that the improved
      resolution afforded by Asymptotical Surprise leads to a different classification
      compared to current methods.

PMID- 27865920
TI  - Temporally correlated fluctuations drive epileptiform dynamics.
AB  - Macroscopic models of brain networks typically incorporate assumptions regarding
      the characteristics of afferent noise, which is used to represent input from
      distal brain regions or ongoing fluctuations in non-modelled parts of the brain.
      Such inputs are often modelled by Gaussian white noise which has a flat power
      spectrum. In contrast, macroscopic fluctuations in the brain typically follow a
      1/fb spectrum. It is therefore important to understand the effect on brain
      dynamics of deviations from the assumption of white noise. In particular, we wish
      to understand the role that noise might play in eliciting aberrant rhythms in the
      epileptic brain. To address this question we study the response of a neural mass
      model to driving by stochastic, temporally correlated input. We characterise the
      model in terms of whether it generates "healthy" or "epileptiform" dynamics and
      observe which of these dynamics predominate under different choices of temporal
      correlation and amplitude of an Ornstein-Uhlenbeck process. We find that certain
      temporal correlations are prone to eliciting epileptiform dynamics, and that
      these correlations produce noise with maximal power in the delta and theta bands.
      Crucially, these are rhythms that are found to be enhanced prior to seizures in
      humans and animal models of epilepsy. In order to understand why these rhythms
      can generate epileptiform dynamics, we analyse the response of the model to
      sinusoidal driving and explain how the bifurcation structure of the model gives
      rise to these findings. Our results provide insight into how ongoing fluctuations
      in brain dynamics can facilitate the onset and propagation of epileptiform
      rhythms in brain networks. Furthermore, we highlight the need to combine large
      scale models with noise of a variety of different types in order to understand
      brain (dys-)function.

PMID- 27865922
TI  - Low-frequency cortical oscillations are modulated by temporal prediction and
      temporal error coding.
AB  - Monitoring and updating temporal predictions are critical abilities for adaptive
      behavior. Here, we investigated whether neural oscillations are related to
      violation and updating of temporal predictions. Human participants performed an
      experiment in which they had to generate a target at an expected time point, by
      pressing a button while taking into account a variable delay between the act and
      the stimulus occurrence. Our behavioral results showed that participants quickly
      adapted their temporal predictions in face of an error. Concurrent
      electrophysiological (EEG) data showed that temporal errors elicited markers that
      are classically related to error coding. Furthermore, intertrial phase coherence
      of frontal theta oscillations was modulated by error magnitude, possibly indexing
      the degree of surprise. Finally, we found that delta phase at stimulus onset was
      correlated with future behavioral adjustments. Together, our findings suggest
      that low frequency oscillations play a key role in monitoring and in updating
      temporal predictions.

PMID- 27865923
TI  - Deriving reproducible biomarkers from multi-site resting-state data: An Autism
      based example.
AB  - Resting-state functional Magnetic Resonance Imaging (R-fMRI) holds the promise to
      reveal functional biomarkers of neuropsychiatric disorders. However, extracting
      such biomarkers is challenging for complex multi-faceted neuropathologies, such
      as autism spectrum disorders. Large multi-site datasets increase sample sizes to
      compensate for this complexity, at the cost of uncontrolled heterogeneity. This
      heterogeneity raises new challenges, akin to those face in realistic diagnostic
      applications. Here, we demonstrate the feasibility of inter-site classification
      of neuropsychiatric status, with an application to the Autism Brain Imaging Data
      Exchange (ABIDE) database, a large (N=871) multi-site autism dataset. For this
      purpose, we investigate pipelines that extract the most predictive biomarkers
      from the data. These R-fMRI pipelines build participant-specific connectomes from
      functionally-defined brain areas. Connectomes are then compared across
      participants to learn patterns of connectivity that differentiate typical
      controls from individuals with autism. We predict this neuropsychiatric status
      for participants from the same acquisition sites or different, unseen, ones. Good
      choices of methods for the various steps of the pipeline lead to 67% prediction
      accuracy on the full ABIDE data, which is significantly better than previously
      reported results. We perform extensive validation on multiple subsets of the data
      defined by different inclusion criteria. These enables detailed analysis of the
      factors contributing to successful connectome-based prediction. First, prediction
      accuracy improves as we include more subjects, up to the maximum amount of
      subjects available. Second, the definition of functional brain areas is of
      paramount importance for biomarker discovery: brain areas extracted from large R
      fMRI datasets outperform reference atlases in the classification tasks.

PMID- 27865919
TI  - Differential stress induced c-Fos expression and identification of region
      specific miRNA-mRNA networks in the dorsal raphe and amygdala of high
      responder/low-responder rats.
AB  - Chronic stress triggers a variety of physical and mental health problems, and how
      individuals cope with stress influences risk for emotional disorders. To
      investigate molecular mechanisms underlying distinct stress coping styles, we
      utilized rats that were selectively-bred for differences in emotionality and
      stress reactivity. We show that high novelty responding (HR) rats readily bury a
      shock probe in the defensive burying test, a measure of proactive stress coping
      behavior, while low novelty responding (LR) rats exhibit enhanced immobility, a
      measure of reactive coping. Shock exposure in the defensive burying test elicited
      greater activation of HR rats' caudal dorsal raphe serotonergic cells compared to
      LRs, but lead to more pronounced activation throughout LRs' amygdala (lateral,
      basolateral, central, and basomedial nuclei) compared to HRs. RNA-sequencing
      revealed 271 mRNA transcripts and 33 microRNA species that were differentially
      expressed in HR/LR raphe and amygdala. We mapped potential microRNA-mRNA networks
      by correlating and clustering mRNA and microRNA expression and identified
      networks that differed in either the HR/LR dorsal raphe or amygdala. A dorsal
      raphe network linked three microRNAs which were down-regulated in LRs (miR-206
      3p, miR-3559-5p, and miR-378a-3p) to repression of genes related to microglia and
      immune response (Cd74, Cyth4, Nckap1l, and Rac2), the genes themselves were up
      regulated in LR dorsal raphe. In the amygdala, another network linked miR-124-5p,
      miR-146a-5p, miR-3068-3p, miR-380-5p, miR-539-3p, and miR-7a-1-3p with repression
      of chromatin remodeling-related genes (Cenpk, Cenpq, Itgb3bp, and Mis18a).
      Overall this work highlights potential drivers of gene-networks and downstream
      molecular pathways within the raphe and amygdala that contribute to individual
      differences in stress coping styles and stress vulnerabilities.

PMID- 27865924
TI  - Effects of a coordinated farmland bird conservation project on farmers'
      intentions to implement nature conservation practices - Evidence from the Swedish
      Volunteer & Farmer Alliance.
AB  - To increase the efficacy of agri-environmental schemes (AES), as well as farmers'
      environmental engagement, practitioners are increasingly turning to collective
      forms of agri-environmental management. As yet, empirical evidence from such
      approaches is relatively scarce. Here, we examined a farmland bird conservation
      project coordinated by BirdLife Sweden, the Swedish Volunteer & Farmer Alliance
      (SVFA). The key features of the SVFA were farmland bird inventories from
      volunteering birdwatchers and on-farm visits to individual farmers from
      conservation advisors for guidance on AES as well as unsubsidised practices.
      Using an ex-post application of the theory of planned behaviour across project
      participants and a randomly sampled control group of farmers we assessed how SVFA
      affected behavioural intentions relating to AES and unsubsidised conservation,
      and how the behaviour was affected by attitudes, perceived social norms and
      perceived behavioural control. We also included a measure of self-identity as a
      conservationist to assess its importance for behavioural intentions, and if SVFA
      stimulated this self-identity. SVFA farmers reported greater commitment to
      implementing AES and unsubsidised conservation, as compared to the control group.
      However, greater commitment was associated with more positive attitudes for
      unsubsidised conservation only and not for AES, underlining the inability of
      existing AES to prompt intrinsic motivation. There were also differences between
      farmers within SVFA, where farmers applying to the project were motivated by
      social influences, while farmers recruited by project managers were motivated by
      their personal beliefs regarding nature conservation. Finally, farmers' self
      perceived ability to perform practices (i.e. perceived behavioural control) was
      important for their commitment to implementing AES as well as unsubsidised
      practices. Therefore, increasing farmers' awareness regarding the availability
      and, not least, practicability of available conservation options may be the key
      to successful biodiversity conservation in agricultural systems.

PMID- 27865925
TI  - Orai1 and Orai2 mediate store-operated calcium entry that regulates HL60 cell
      migration and FAK phosphorylation.
AB  - Store-operated Ca2+ entry (SOCE) is a major mechanism for the regulation of
      intracellular Ca2+ homeostasis and cellular function. Emerging evidence has
      revealed that altered expression and function of the molecular determinants of
      SOCE play a critical role in the development or maintenance of several cancer
      hallmarks, including enhanced proliferation and migration. Here we show that, in
      the acute myeloid leukemia cell line HL60, Orai2 is highly expressed at the
      transcript level, followed by the expression of Orai1. Using fluorescence Ca2+
      imaging we found that Orai2 silencing significantly attenuated thapsigargin
      induced SOCE, as well as knockdown of Orai1, while silencing the expression of
      both channels almost completely reduced SOCE, thus suggesting that SOCE in these
      cells is strongly dependent on Orai1 and Orai2. On the other hand, the expression
      of TRPC1, TRPC3 and TRPC6 is almost absent at the transcript and protein level.
      Bromodeoxyuridine cell proliferation assay revealed that Orai1 and Orai2
      expression silencing significantly reduced HL60 cell proliferation. Furthermore,
      knockdown of Orai1 and Orai2 significantly attenuated the ability of HL60 to
      migrate in vitro as determined by transwell migration assay, probably due to the
      impairment of FAK tyrosine phosphorylation. These findings provide evidence for a
      role for Orai1 and Orai2, in SOCE and migration in the human HL60 promyeloblastic
      cell line. This article is part of a Special Issue entitled: ECS Meeting edited
      by Claus Heizmann, Joachim Krebs and Jacques Haiech.

PMID- 27865926
TI  - Emerin suppresses Notch signaling by restricting the Notch intracellular domain
      to the nuclear membrane.
AB  - Emerin is an inner nuclear membrane protein that is involved in maintaining the
      mechanical integrity of the nuclear membrane. Increasing evidence supports the
      involvement of emerin in the regulation of gene expression; however, its precise
      function remains to be elucidated. Here, we show that emerin downregulated genes
      downstream of Notch signaling, which are activated exclusively by the Notch
      intracellular domain (NICD). Deletion mutant experiments revealed that the
      transmembrane domain of emerin is important for the inhibition of Notch
      signaling. Emerin interacted directly and colocalized with the NICD at the
      nuclear membrane. Emerin knockdown induced the phosphorylation of ERK and AKT,
      increased endogenous Notch signaling, and inhibited hydrogen peroxide-induced
      apoptosis in HeLa cells. Notably, the downregulation of barrier-to
      autointegration factor (BAF) or lamin A/C increased Notch signaling by inducing
      the release of emerin into the cytosol, implying that nuclear membrane-bound
      emerin acts as an endogenous inhibitor of Notch signaling. Taken together, our
      results indicate that emerin negatively regulates Notch signaling by promoting
      the retention of the NICD at the nuclear membrane. This mechanism could
      constitute a new therapeutic target for the treatment of emerin-related diseases.

PMID- 27865927
TI  - Structural perturbations induced by Asn131 and Asn171 glycosylation converge
      within the EFSAM core and enhance stromal interaction molecule-1 mediated store
      operated calcium entry.
AB  - A major intracellular calcium (Ca2+) uptake pathway in both excitable and non
      excitable eukaryotic cells is store-operated Ca2+ entry (SOCE). SOCE is the
      process by which endoplasmic reticulum (ER)-stored Ca2+ depletion leads to
      activation of plasma membrane Ca2+ channels to provide a sustained increase in
      cytosolic Ca2+ levels that mediate a plethora of physiological processes ranging
      from the immune response to platelet aggregation. Stromal interaction molecule-1
      (STIM1) is the principal regulator of SOCE and responds to changes in ER stored
      Ca2+ through luminal sensing machinery composed of EF-hand and SAM domains
      (EFSAM). The EFSAM domain can undergo N-glycosylation at Asn131 and Asn171 sites;
      however, the precise role of EFSAM N-glycosylation in the Ca2+ sensing mechanism
      of STIM1 is unclear. By establishing a site-specific chemical approach to
      covalently linking glucose to EFSAM and examining alpha-helicity, thermal
      stability, three dimensional atomic-resolution structure, Ca2+ binding affinity
      and oligomerization, we show that N-glycosylation of the EFSAM domain enhances
      the properties that promote STIM1 activation. This augmentation occurs through
      changes in structure localized near the Asn131 and Asn171 sites that together
      permeate through the protein core and lead to decreased Ca2+ binding affinity,
      reduced stability and enhanced oligomerization. Congruently, Ca2+ influx via SOCE
      in HEK293 cells co-expressing Orai1 and STIM1 was diminished when N-glycosylation
      was blocked by introducing Asn131Gln and Asn171Gln mutations. Collectively, our
      data suggests that N-glycosylation enhances the EFSAM destabilization-coupled
      oligomerization in response to ER Ca2+ depletion thereby augmenting the role of
      STIM1 as a robust ON/OFF regulator of SOCE. This article is part of a Special
      Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques
      Haiech.

PMID- 27865929
TI  - G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of
      triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me, Et, and
      iPr, during zebrafish development.
AB  - Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3),
      were previously shown to be significantly cytotoxic toward HT-29 cancer cells and
      to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1
      activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused
      apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein
      kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial
      cytochrome c measurements and annexin V screening, confirming apoptotic pathways
      of cell death. Cell cycle analysis showed the majority of treated HT-29 cells
      were arrested at the G2/M checkpoint after 24h; results of both assays were
      confirmed by changes in populations of relevant genes (PCR array analysis). Cell
      invasion studies showed inhibition of metastasis through MatrigelTM matrix to 17
      22% cf. untreated cells. LC50 values were determined in zebrafish (8.36, 8.17,
      and 7.64MUM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to
      0.625MUM, and 3 was tolerated at even higher doses of up to 1.25MUM.

PMID- 27865928
TI  - The SWI2/SNF2 Chromatin-Remodeling ATPase BRAHMA Regulates Chlorophyll
      Biosynthesis in Arabidopsis.
AB  - Chlorophyll biosynthesis is critical for chloroplast development and
      photosynthesis in plants. Although reactions in the chlorophyll biosynthetic
      pathway have been largely known, little is known about the regulatory mechanisms
      of this pathway. In this study, we found that the dark-grown knockout and
      knockdown mutants as well as RNA-interference transgenic seedlings of BRAHMA
      (BRM), which encodes an SWI2/SNF2 chromatin-remodeling ATPase, had higher
      greening rates, accumulated less protochlorophyllide, and produced less reactive
      oxygen species than Arabidopsis wild-type plants did upon light exposure. The
      expression of NADPH:protochlorophyllide oxidoreductase A (PORA), PORB, and PORC,
      which catalyze a key step in chlorophyll biosynthesis, was increased in the brm
      mutants. We found that BRM physically interacted with the bHLH transcription
      factor PHYTOCHROME-INTERACTING FACTOR 1 (PIF1) through its N-terminal domains.
      Furthermore, we demonstrated that BRM was directly recruited to the cis
      regulatory regions of PORC, but not of PORA and PORB, at least partially in a
      PIF1-dependent manner and the level of histone H3 lysine 4 tri-methylation
      (H3K4me3) at PORC loci was increased in the brm mutant. Taken together, our data
      indicate that the chromatin-remodeling enzyme BRM modulates PORC expression
      through interacting with PIF1, providing a novel regulatory mechanism by which
      plants fine-tune chlorophyll biosynthesis during the transition from
      heterotrophic to autotrophic growth.

PMID- 27865930
TI  - Evaluation of different in vitro dissolution tests based on level A in vitro-in
      vivo correlations for fenofibrate self-emulsifying lipid-based formulations.

PMID- 27865931
TI  - Multifunctional adhesive polymers: Preactivated thiolated chitosan-EDTA
      conjugates.
AB  - AIM: The aim of this study was to synthesis preactivated thiolated chitosan-EDTA
      (Ch-EDTA-cys-2MNA) conjugates exhibiting in particular high mucoadhesive,
      cohesive and chelating properties. METHODS: Thiol groups were coupled with
      chitosan by carbodiimide reaction and further preactivated by attachment with 2
      mercaptonicotinic acid (2MNA) via disulfide bond formation. Determinations of
      primary amino and sulfhydryl groups were performed by TNBS and Ellman's tests,
      respectively. Cytotoxicity was screened by resazurin assay in Caco-2 cells.
      Mucoadhesive properties and bivalent cation binding capacity with Mg2+ and Ca2+
      in comparison to chitosan-EDTA (Ch-EDTA) and thiolated Ch-EDTA (Ch-EDTA-cys) were
      evaluated. RESULTS: Determination of 2MNA and total sulfhydryl groups indicated
      that 80% of thiol groups were preactivated. The results from cytotoxicity studies
      demonstrated that Ch-EDTA-cys and Ch-EDTA-cys-2MNA were not toxic to the cells at
      the polymer test concentration of 0.25% (w/v) while cell viability decreased by
      increasing the concentration of Ch-EDTA. Although EDTA molecule was modified by
      thiolation and preactivation, approximately 50% of chelating properties of the
      conjugates were maintained compared to Ch-EDTA. Ch-EDTA-cys-2MNA adhered on
      freshly excised porcine intestinal mucosa up to 6h while Ch-EDTA adhered for just
      1h. CONCLUSION: According to the combination of mucoadhesive and chelating
      properties of the conjugates synthesized in this study, Ch-EDTA-cys-2MNA might be
      useful for various mucosal drug delivery systems.

PMID- 27865934
TI  - Prediction of intraocular antibody drug stability using ex-vivo ocular model.
AB  - Following intravitreal (IVT) injection, therapeutic proteins get exposed to
      physiological pH, temperature and components in the vitreous humor (VH) for a
      significantly long time. Therefore, it is of interest to study the stability of
      the proteins in the VH. However, the challenge posed by the isolated VH (such as
      pH shift upon isolation and incubation due to the formation of smaller molecular
      weight (MW) degradation products) can result in artefacts when investigating
      protein stability in relevance for the actual in vivo situation. In this current
      study, an ex-vivo intravitreal horizontal stability model (ExVit-HS) has been
      successfully developed and an assessment of long-term stability of a bi-specific
      monoclonal antibody (mAb) drug in the isolated VH for 3months at physiological
      conditions has been conducted. The stability assessment was performed using
      various analytical techniques such as microscopy, UV visible for protein content,
      target binding ELISA, Differential Scanning Calorimetry (DSC), Capillary
      electrophoresis-SDS, Size Exclusion (SEC) and Ion-exchange chromatography (IEC)
      and SPR-Biacore. The results show that the ExVit-HS model was successful in
      maintaining the VH at physiological conditions and retained a majority of protein
      in the VH-compartment throughout the study period. The mAb exhibited
      significantly less fragmentation in the VH relative to the PBS control; however,
      chemical stability of the mAb was equally compromised in VH and PBS.
      Interestingly, in the PBS control, mAb showed a rapid linear loss in the binding
      affinity. The loss in binding was almost 20% higher compared to that in VH after
      3months. The results clearly suggest that the mAb has different degradation
      kinetics in the VH compared to PBS. These results suggest that it is beneficial
      to investigate the stability in the VH for drugs intended for IVT injection and
      that are expected longer residence times in the VH. The studies show that the
      ExVit-HS model may become a valuable tool for evaluating stability of protein
      drugs and other molecules following IVT injection.

PMID- 27865933
TI  - Mechanistic analysis of triamcinolone acetonide release from PLGA microspheres as
      a function of varying in vitro release conditions.
AB  - In vitro tests for controlled release PLGA microspheres in their current state
      often do not accurately predict in vivo performance of these products during
      formulation development. Here, we introduce a new mechanistic and multi-phase
      approach to more clearly understand in vitro-in vivo relationships, and describe
      the first "in vitro phase" with the model drug, triamcinolone acetonide (Tr-A).
      Two microsphere formulations encapsulating Tr-A were prepared from PLGAs of
      different molecular weights and end-capping (18kDa acid-capped and 54kDa ester
      capped). In vitro release kinetics and the evidence for controlling mechanisms
      (i.e., erosion, diffusion, and water-mediated processes) were studied in four
      release media: PBST pH 7.4 (standard condition), PBST pH 6.5, PBS+1.0% triethyl
      citrate (TC), and HBST pH 7.4. The release mechanism in PBST was primarily
      polymer erosion-controlled as indicated by the similarity of release and mass
      loss kinetics. Release from the low MW PLGA was accelerated at low pH due to
      increased rate of hydrolysis and in the presence of the plasticizer TC due to
      slightly increased hydrolysis and much higher diffusion in the polymer matrix. TC
      also increased release from the high MW PLGA due to increased hydrolysis,
      erosion, and diffusion. This work demonstrates how in vitro conditions can be
      manipulated to change not only rates of drug release from PLGA microspheres but
      also the mechanism(s) by which release occurs. Follow-on studies in the next
      phases of this approach will utilize these results to compare the mechanistic
      data of the Tr-A/PLGA microsphere formulations developed here after recovery of
      microspheres in vivo. This new approach based on measuring mechanistic indicators
      of release in vitro and in vivo has the potential to design better, more
      predictive in vitro release tests for these formulations and potentially lead to
      mechanism-based in vitro-in vivo correlations.

PMID- 27865932
TI  - Oral Helicobacter pylori vaccine-encapsulated acid-resistant HP55/PLGA
      nanoparticles promote immune protection.
AB  - Oral vaccination, is notoriously weak or nonimmunogenic. One of the major reasons
      is the inefficient antigen uptake caused by enzymolysis and hydrolysis in the
      gastrointestinal tract. In this study, acid-resistant HP55/PLGA nanoparticle was
      developed as an oral delivery system to protect H. pylori recombinant antigen CCF
      against the complex gastrointestinal environment. These ~200nm particles
      controlled the release of antigen in the acidic environment (pH?5.5). Immunized
      mice with HP55/PLGA-CCF nanoparticles induced high levels of urease-specific
      antibodies and memory T cell responses. A month after H. pylori challenge, 43% of
      mice were completely protected. The protection was highly associated with the
      Th1/Th17-bias immune response, which had been recognized as an optimal immunity
      against H. pylori infection. In addition, a mass of T-cells were observed in the
      lamina propria of mice immunized with CCF, especially in the HP55/PLGA-CCF
      nanoparticles administered recipients, and contributed to the development of
      postimmunization gastritis. These results indicate that oral immunization with
      acid-resistant HP55/PLGA nanoparticles encapsulating vaccine antigens represent a
      promising strategy for antigen protection, slow-release and targeting, and thus
      prevented gastrointestinal infection.

PMID- 27865935
TI  - Controlling successive ionic layer absorption and reaction cycles to optimize
      silver nanoparticle-induced localized surface plasmon resonance effects on the
      paper strip.
AB  - This study investigates why a silver nanoparticle (SNP)-induced surface-enhanced
      Raman scattering (SERS) paper chip fabricated at low successive ionic layer
      absorption and reaction (SILAR) cycles leads to a high SERS enhancement factor
      (7*108) with an inferior nanostructure and without generating a hot spot effect.
      The multi-layered structure of SNPs on cellulose fibers, verified by magnified
      scanning electron microscopy (SEM) and analyzed by a computational simulation
      method, was hypothesized as the reason. The pattern of simulated local electric
      field distribution with respect to the number of SILAR cycles showed good
      agreement with the experimental Raman intensity, regardless of the wavelength of
      the excitation laser sources. The simulated enhancement factor at the 785-nm
      excitation laser source (2.8*109) was 2.5 times greater than the experimental
      enhancement factor (1.1*109). A 532-nm excitation laser source exhibited the
      highest maximum local electric field intensity (1.9*1011), particularly at the
      interparticle gap called a hot spot. The short wavelength led to a strong
      electric field intensity caused by strong electromagnetic coupling arising from
      the SNP-induced local surface plasmon resonance (LSPR) effects through high
      excitation energy. These findings suggest that our paper-based SILAR-fabricated
      SNP-induced LSPR model is valid for understanding SNP-induced LSPR effects.

PMID- 27865937
TI  - Lipopolysaccharide induces proliferation and osteogenic differentiation of
      adipose-derived mesenchymal stromal cells in vitro via TLR4 activation.
AB  - Multipotent mesenchymal stromal cells (MSC) are capable of multi-lineage
      differentiation and support regenerative processes. In bacterial infections,
      resident MSC can come intocontact with and need to react to bacterial components.
      Lipopolysaccharide (LPS), a typical structure of Gram-negative bacteria,
      increases the proliferation and osteogenic differentiation of MSC. LPS is usually
      recognized by the toll-like receptor (TLR) 4 and induces pro-inflammatory
      reactions in numerous cell types. In this study, we quantified the protein
      expression of TLR4 and CD14 on adipose-derived MSC (adMSC) in osteogenic
      differentiation and investigated the effect of TLR4 activation by LPS on NF
      kappaB activation, proliferation and osteogenic differentiation of adMSC. We
      found that TLR4 is expressed on adMSC whereas CD14 is not, and that osteogenic
      differentiation induced an increase of the amount of TLR4 protein whereas LPS
      stimulation did not. Moreover, we could show that NF-kappaB activation via TLR4
      occurs upon LPS treatment. Furthermore, we were able to show that competitive
      inhibition of TLR4 completely abolished the stimulatory effect of LPS on the
      proliferation and osteogenic differentiation of adMSC. In addition, the
      inhibition of TLR4 leads to the complete absence of osteogenic differentiation of
      adMSC, even when osteogenically stimulated. Thus, we conclude that LPS induces
      proliferation and osteogenic differentiation of adMSC in vitro through the
      activation of TLR4 and that the TLR4 receptor seems to play a role during
      osteogenic differentiation of adMSC.

PMID- 27865936
TI  - Constitutive beta-catenin activation in osteoblasts impairs terminal osteoblast
      differentiation and bone quality.
AB  - Accumulating evidence suggests that Wnt/beta-catenin signaling plays a central
      role in controlling bone mass. We previously reported that constitutive
      activation of beta-catenin (CA-beta-catenin) in osteoblasts potentially has side
      effects on the bone growth and bone remodeling process, although it could
      increase bone mass. The present study aimed to observe the effects of
      osteoblastic CA-beta-catenin on bone quality and to investigate possible
      mechanisms of these effects. It was found that CA-beta-catenin mice exhibited
      lower mineralization levels and disorganized collagen in long bones as confirmed
      by von Kossa staining and sirius red staining, respectively. Also, bone strength
      decreased significantly in CA-beta-catenin mice. Then the effect of CA-beta
      catenin on biological functions of osteoblasts were investigated and it was found
      that the expression levels of osteocalcin, a marker for the late differentiation
      of osteoblasts, decreased in CA-beta-catenin mice, while the expression levels of
      osterix and alkaline phosphatase, two markers for the early differentiation of
      osteoblasts, increased in CA-beta-catenin mice. Furthermore, higher proliferation
      rate were revealed in osteoblasts that were isolated from CA-beta-catenin mice.
      The Real-time PCR and western blot examination found that the expression level of
      c-myc and cyclin D1, two G1 progression-related molecules, increased in
      osteoblasts that were isolated from the CA-beta-catenin mice, and the expression
      levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate
      cells entering into S and G2/M phases, increased in osteoblasts that were
      isolated from the CA-beta-catenin mice. In summary, osteoblastic CA-beta-catenin
      kept osteoblasts in high proliferative state and impaired the terminal osteoblast
      differentiation, and this led to changed bone structure and decreased bone
      strength.

PMID- 27865938
TI  - PDMP, a ceramide analogue, acts as an inhibitor of mTORC1 by inducing its
      translocation from lysosome to endoplasmic reticulum.
AB  - Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is a master
      regulator of cell growth, metabolism, and cell differentiation. Recent studies
      have revealed that the recruitment of mTORC1 to lysosomes is essential for its
      activation. The ceramide analogue 1-phenyl-2-decanoylamino-3-morpholino-1
      propanol (PDMP), a well known glycosphingolipid synthesis inhibitor, also affects
      the structures and functions of various organelles, including lysosomes and
      endoplasmic reticulum (ER). We investigated whether PDMP regulates the mTORC1
      activity through its effects on organellar behavior. PDMP induced the
      translocation of mTORC1 from late endosomes/lysosomes, leading to the
      dissociation of mTORC1 from its activator Rheb in MC3T3-E1 cells. Surprisingly,
      we found mTORC1 translocation to the ER upon PDMP treatment. This effect of PDMP
      was independent of its action as the inhibitor, since two stereoisomers of PDMP,
      with and without the inhibitor activity, showed essentially the same effect. We
      confirmed that PDMP inhibits the mTORC1 activity based on the decrease in the
      phosphorylation of ribosomal S6 kinase, a downstream target of mTORC1, and the
      increase in LC3 puncta, reflecting autophagosome formation. Furthermore, PDMP
      inhibited the mTORC1-dependent osteoblastic cell proliferation and
      differentiation of MC3T3-E1 cells. Accordingly, the present results reveal a
      novel mechanism of PDMP, which inhibits the mTORC1 activity by inducing the
      translocation of mTOR from lysosomes to the ER.

PMID- 27865940
TI  - Alterations in nasal mucociliary activity in polycystic ovary syndrome.
AB  - OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in
      women of reproductive age. It can affect various organ systems, and respiratory
      mucosa has been reported as being hormone responsive. STUDY DESIGN: A case
      control study consisting of 50 women with PCOS and 30 control subjects matched
      for age and body mass index was conducted, in order to investigate nasal
      mucociliary clearance time (NMCT) in patients with PCOS. Serum basal hormonal
      biochemical parameters and NMCT were evaluated on menstrual cycle days 2-5 for
      all participants. RESULTS: The mean NMCT in PCOS and control groups was 10.45+/
      2.88 and 6.92+/-1.78, respectively (p=0.0001). A significant positive correlation
      was found between NMCT and duration of disease (r=0.52; p=0.001), serum total
      testosterone level (r=0.28; p=0.04), and luteinizing hormone/follicle stimulating
      hormone (r=0.29; p=0.04). CONCLUSIONS: Our findings indicate that PCOS is
      associated with altered NMCT. Prolonged NMCT predisposes patients to respiratory
      tract and middle ear infections, and clinicians should be aware of this.

PMID- 27865939
TI  - C-reactive protein response is higher in early than in late ovarian
      hyperstimulation syndrome.
AB  - OBJECTIVES: Many in vitro fertilization (IVF) complications are inflammatory by
      nature, some of which are even life-threatening. We evaluated the response of C
      reactive protein (CRP) in IVF complications, especially in early and late ovarian
      hyperstimulation syndrome (OHSS), to support clinical decision making in
      gynecological emergency policlinics. STUDY DESIGN: In a prospective two-year
      study at Helsinki University Hospital, Finland, we recruited patients with IVF
      complications including moderate or severe OHSS (n=47 patients: 36 early and 14
      late OHSS cases), or other IVF complications (n=13). As controls, we recruited
      women in an uncomplicated IVF cycle (n=27). Serial blood samples (CRP, blood
      count, platelets, albumin, estradiol, creatinine, and electrolytes) were
      collected from patients upon admission to the emergency polyclinic and during and
      after treatment on the ward, and from the controls prior, during, and after the
      IVF protocol. All samples were categorized according to oocyte pick-up (OPU). The
      statistics included comparisons between and within the study groups, and receiver
      operating characteristic (ROC) curve analysis for diagnostic accuracy of CRP for
      early OHSS at emergency polyclinics. RESULTS: On admission, CRP did not
      differentiate OHSS from other IVF complications, but CRP was higher in early
      (median 21; IQR 8-33mg/L) than in late (6; 3-9mg/L, p=0.001) OHSS. In ROC
      analysis for CRP (12mg/L), the area under the curve (AUC) was 0.74 (p=0.001) with
      sensitivity of 69% and specificity of 71% for early OHSS. CRP was significantly
      higher (28; 10-46mg/L) in patients with early OHSS two days after oocyte pick-up
      (OPU) than in the controls (5; <3-9mg/L, p<0.001). The level normalized by 12
      days, similarly to the controls. On the ward, the peak CRP was higher if early
      OHSS was complicated with infection (108; 49-166mg/L) than without infection (20;
      8-32mg/L, p=0.001). Late OHSS was associated with hypoalbuminemia (19.6; 16.2
      23.1g/L, p<0.001) and thrombocytosis (494; 427-561 E9/L, p=0.004; comparisons to
      early OHSS). CONCLUSIONS: Early OHSS associates with a distinct rise in CRP level
      beyond that induced by uncomplicated oocyte pick-up, whereas the CRP levels in
      late OHSS are comparable to those in the control cycles. CRP identifies, but
      cannot distinguish IVF complications.

PMID- 27865941
TI  - Local injection of diluted vasopressin followed by suction curettage for cervical
      ectopic pregnancy.
AB  - OBJECTIVE: To report the results of local injection of diluted vasopressin
      followed by suction curettage as a conservative treatment for women with cervical
      ectopic pregnancy, who wish to preserve their future fertility. STUDY DESIGN:
      This was a retrospective chart review in a university hospital and a municipal
      hospital. We injected diluted vasopressin (Pitressin R, total amount of 4-10
      units) transvaginally into the cervix surrounding the gestational sac, but not
      directly into the gestational sac, and/or the lower segment of the uterine body
      under transvaginal ultrasonographic guidance. After cessation of fetal
      heartbeats, we aspirated the conceptus by performing suction curettage. We
      injected additional vasopressin into the gestational sac in cases with a viable
      fetus after the initial injection. Forced contraction of the cervical smooth
      muscle facilitated removal of the conceptus with minimal blood loss during
      curettage. We measured operative time, total blood loss, complications, and the
      need for additional treatment. RESULTS: We included 11 women. Mean patient age,
      gestational age, and serum human chorionic gonadotrophin (hCG) at the
      intervention were 31.2+/-6.4years, 6.0+/-0.6 weeks, and 18,370+/-21,570 IU/L,
      respectively. Mean size of the gestational sac was 19.6+/-9.5mm. The uterus was
      successfully preserved without any complications in all patients. All procedures
      were completed within 15min except for the first case (range: 5-33min). In 4
      cases, the conceptus containing a gestational sac was spontaneously extruded en
      bloc from the external os after the injection. Additional systematic methotrexate
      administration was required in one case because of remaining villi at the
      implantation site with persistence of serum hCG levels after the procedure.
      CONCLUSION: Local injection of diluted vasopressin and subsequent suction
      curettage is a feasible conservative treatment for cervical ectopic pregnancy.

PMID- 27865942
TI  - Outcomes of laparoscopic sacropexy in women over 70: A comparative study.
AB  - OBJECTIVE: Precise data are lacking concerning laparoscopic sacropexy in the
      elderly population. The purpose of this study was to compare the outcomes and
      complications associated with laparoscopic sacropexy (colpopexy or hysteropexy)
      in women aged under 70 and 70 or over. STUDY DESIGN: Retrospective review of data
      on patients who underwent laparoscopic sacropexy in two tertiary centers. Peri-
      and postoperative complications were recorded and described using the IUGA
      classification. Surgery was considered successful if the patient was
      symptomatically satisfied or very satisfied and if the POP-Q (Pelvic Organ
      Prolapse-Quantification) stage score at the follow-up visit was below stage 2 for
      all compartments. RESULTS: Among the 191 women studied, 47 (24.6%) were aged 70
      or more. According to the ICS/IUGA classification of POP complications,
      perioperative and postoperative complication rates were similar in the older
      versus younger groups (bladder injuries (0 vs. 1.39%, p=1) (4A T1 S2), rectal
      injuries (0% vs. 0.69%, p=1) (5BT1S5), vaginal injuries (2.13% vs. 0%, p=0.246)
      (2A T1 S1)). No laparotomy conversion was required in either group. At two months
      of follow-up, the success rate was 97.9% and 95.1% in the older and younger
      groups, respectively (p=0.68). At 24 months of follow-up, the overall reoperation
      rate was 12.8% for the older group versus 11.8% in the younger group (p=0.80).
      CONCLUSIONS: Our findings suggest that laparoscopic sacropexy is a valid option
      in elderly women presenting with genital prolapse.

PMID- 27865943
TI  - Association between parity and ovarian reserve in reproductive age women.
AB  - OBJECTIVE: A number of factors affect ovarian reserve. In this study, we
      investigate the association between parity and ovarian reserve in reproductive
      age women. MATERIALS AND METHODS: This cross-sectional study was conducted on 186
      women aged 20-35 years. The participants were divided into two main groups. Group
      A (n=93) included women with at least one parity (pregnancy after 28 weeks),
      while group B (n=93) included women with no history of pregnancy. We evaluated
      the following factors related to ovarian reserve: follicle-stimulating hormone
      (FSH), ovarian antral follicles, anti-Mullerian hormone (AMH), and ovarian
      volume. RESULTS: A total of 186 women with a mean age of 27.83+/-4.49years
      enrolled in this study. There was a difference in mean AMH between the
      nulliparous (2.53+/-1.90ng/ml) and multiparous (3.54+/-1.42ng/ml) groups
      (p<0.001). FSH levels were from 5.27+/-1.8mIU/mL in nulliparous women to 5.01+/
      1.9mIU/mL in multiparous women, which did not significantly differ (p=0.36).
      Antral follicles and ovarian size in multiparous women increased significantly
      (p<0.001). CONCLUSION: Parity has a significant association with higher levels of
      ovarian reserve markers.

PMID- 27865945
TI  - Episiotomy in vacuum-assisted delivery affects the risk of obstetric anal
      sphincter injury: a systematic review and meta-analysis.
AB  - The risk of obstetric anal sphincter injury (OASIS) is increased in vacuum
      assisted delivery. However, it remains unclear whether episiotomy may protect
      against OASIS in this type of delivery. The objective of this study was to assess
      whether mediolateral or lateral episiotomy affects the risk of OASIS in vacuum
      assisted delivery among primiparous women. Data were found searching The PubMed,
      Cochrane library and Embase databases electronically. Studies investigating the
      risk of OASIS in vacuum-assisted delivery with and without the use of
      mediolateral or lateral episiotomy were considered for inclusion. Of the 452
      studies found, 15 observational studies were included in this meta-analysis. All
      authors assessed risk of bias of the included studies using the Scottish
      Intercollegiate Guideline Network (SIGN) quality score. According to this meta
      analysis, mediolateral or lateral episiotomy significantly reduced the risk of
      OASIS in vacuum-assisted deliveries in primiparous women (OR 0.53 (95% CI 0.37
      0.77)). Numbers needed to treat (NNT) was 18.3 (95% CI 17.7-18.9). The protective
      effect of episiotomy seemed most pronounced when performed in more than 75% of
      vacuum-assisted deliveries (OR 0.37 (95% CI 0.15-0.92)). In conclusion, this meta
      analysis showed that mediolateral or lateral episiotomy was protective against
      OASIS and may be considered in vacuum-assisted delivery in primiparous women.
      Randomized controlled trials to further investigate this finding are warranted.

PMID- 27865946
TI  - Are lower antibody responses to influenza vaccination in cytomegalovirus
      seropositive older adults the result of beta adrenergic blockade?

PMID- 27865944
TI  - Misoprostol exposure during the first trimester of pregnancy: Is the malformation
      risk varying depending on the indication?
AB  - OBJECTIVE: To report the prospective follow-up of pregnancies exposed to
      misoprostol during the first trimester and analyse the teratogenic risk depending
      on the indication for use. STUDY DESIGN: Prospective observational study of 265
      women exposed to misoprostol during the first 12 weeks of pregnancy and followed
      until the delivery. Women were included if they or their physician had contacted
      a French pharmacovigilance centre before 22 weeks of gestation (WG) to obtain
      information on the risk of misoprostol exposure, and if there had been
      misoprostol exposure before 13 WG. Data were collected at the time of the first
      contact, and the pregnancy outcome was recorded at follow-up. Women were
      prospectively enrolled from January 1988 to December 2013. RESULTS: The main
      indication for misoprostol was voluntary abortion (60.9%). Ten major
      malformations (5.5%) (95% CI 2.65-9.82%) were reported and five of them were
      consistent with the pattern of malformations attributed to misoprostol: Mobius
      sequence, hydrocephalus, terminal transverse limb reduction associated with a
      clubfoot, syndactyly, and complete posterior encephalocele. The rate of
      malformations was higher, but not significantly, in women exposed to misoprostol
      for voluntary abortion (7.9%) compared with women exposed to misoprostol for
      other or unknown indications (3.2%). CONCLUSIONS: Our results confirmed a
      specific pattern of malformations due to misoprostol use in early pregnancy, even
      with low dose of misoprostol. Despite the small number of cases, we observed a
      higher proportion of major malformations in fetuses born to women who continued
      their pregnancy after a failed voluntary abortion with misoprostol. Further
      studies should be conducted to evaluate other potential factors, such as
      combination treatment with mifepristone and the socio-environmental
      characteristics in this group of women.

PMID- 27865947
TI  - Immune responses in perinatal brain injury.
AB  - The perinatal period has often been described as immune deficient. However, it
      has become clear that immune responses in the neonate following exposure to
      microbes or as a result of tissue injury may be substantial and play a role in
      perinatal brain injury. In this article we will review the immune cell
      composition under normal physiological conditions in the perinatal period, both
      in the human and rodent. We will summarize evidence of the inflammatory responses
      to stimuli and discuss how neonatal immune activation, both in the central
      nervous system and in the periphery, may contribute to perinatal hypoxic-ischemic
      brain injury.

PMID- 27865948
TI  - Neuronal Fc-epsilon receptor I contributes to antigen-evoked pruritus in a murine
      model of ocular allergy.
AB  - Pruritus is the major symptom of ocular allergy but currently available
      treatments are often ineffective. Previous studies demonstrated that
      subpopulations of primary sensory neurons express Fc receptors and may contribute
      to antigen-specific pain. We investigated the role of neuronal Fc-epsilon
      Receptor I (FcepsilonRI) in allergic ocular pruritus. Ovalbumin (OVA) was used as
      allergen together with alum adjuvant (OVA+alum) to produce a mouse model of
      ocular allergy with a significant elevation in the serum levels of both antigen
      specific IgE and IgG. Mice sensitized by OVA without alum only induced elevation
      of serum IgG but not IgE. Scratching behavior toward the eyes with the hindlimb
      was used as an indicator of ocular itch. Topical OVA challenging to the eye dose
      dependently induced scratching toward the eye in the OVA+alum sensitized mice,
      but not those sensitized by OVA only. The antigen-induced scratching was largely
      abolished by topical application of the blocking antibody to FcepsilonRIalpha,
      but was only partially alleviated by pretreatment of mast cell stabilizer or
      histamine I receptor antagonist. The expression of FcepsilonRI was detected in
      subpopulations of trigeminal ganglion (TG) neurons including those expressing
      pruriceptive markers and innervating the conjunctiva in the naive mice. Moreover,
      FcepsilonRI was found significantly upregulated in small-sized TG neurons in the
      OVA+alum sensitized mice. In acutely dissociated TG neurons, IgE-immune complex
      (IC), but not the antibody or antigen alone, induced intracellular calcium
      increase. The neuronal responses to IgE-IC could be specifically blocked by pre
      application of a siRNA for FcepsilonRIalpha. Our results indicate that
      FcepsilonRI expressed on peripheral nociceptive neurons in the TG may be directly
      activated by IgE-IC and contribute to allergic ocular pruritus. This study may
      suggest a novel mechanism for the development of pathological itch in allergic
      diseases.

PMID- 27865949
TI  - Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1)
      fails to modulate stress or cognitive performance in healthy male subjects.
AB  - BACKGROUND: Preclinical studies have identified certain probiotics as
      psychobiotics - live microorganisms with a potential mental health benefit.
      Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour,
      corticosterone release and alter central expression of GABA receptors in an
      anxious mouse strain. However, it is unclear if this single putative psychobiotic
      strain has psychotropic activity in humans. Consequently, we aimed to examine if
      these promising preclinical findings could be translated to healthy human
      volunteers. OBJECTIVES: To determine the impact of L. rhamnosus on stress-related
      behaviours, physiology, inflammatory response, cognitive performance and brain
      activity patterns in healthy male participants. METHODS: An 8week, randomized,
      placebo-controlled, cross-over design was employed. Twenty-nine healthy male
      volunteers participated. Participants completed self-report stress measures,
      cognitive assessments and resting electroencephalography (EEG). Plasma IL10,
      IL1beta, IL6, IL8 and TNFalpha levels and whole blood Toll-like 4 (TLR-4) agonist
      induced cytokine release were determined by multiplex ELISA. Salivary cortisol
      was determined by ELISA and subjective stress measures were assessed before,
      during and after a socially evaluated cold pressor test (SECPT). RESULTS: There
      was no overall effect of probiotic treatment on measures of mood, anxiety, stress
      or sleep quality and no significant effect of probiotic over placebo on
      subjective stress measures, or the HPA response to the SECPT. Visuospatial memory
      performance, attention switching, rapid visual information processing, emotion
      recognition and associated EEG measures did not show improvement over placebo. No
      significant anti-inflammatory effects were seen as assessed by basal and
      stimulated cytokine levels. CONCLUSIONS: L. rhamnosus was not superior to placebo
      in modifying stress-related measures, HPA response, inflammation or cognitive
      performance in healthy male participants. These findings highlight the challenges
      associated with moving promising preclinical studies, conducted in an anxious
      mouse strain, to healthy human participants. Future interventional studies
      investigating the effect of this psychobiotic in populations with stress-related
      disorders are required.

PMID- 27865950
TI  - Lactobacillus sps. lipase mediated poly (epsilon-caprolactone) degradation.
AB  - Polymer degradation through lipase appears to be an enthralling alternative to
      bulk chemical routes. Poly (epsilon-caprolactone) (PCL) is an artificial
      polyester that can be degraded by microbes and enzymes like lipases and
      esterases. The environmental degradation of PCL is dependent on the activity of
      bacteria that characterization techniques such as thermogravimetric analysis,
      differential thermal are widely present in the ecosystem. In this study, three
      different lipases derived from Lactobacillus brevis, Lactobacillus plantarum and
      their co-culture have been utilized to explore their efficiency towards PCL
      enzymatic degradation. The effect of parameters such as enzyme loading and
      degradation time has been explored to understand the efficiency of the enzymes
      used in this study. Various analysis, scanning electron microscopy and Fourier
      transform infrared spectroscopy have been employed to study the enzymatic
      degradation and its possible mechanistic insight.

PMID- 27865951
TI  - Renoprotective effect of low-molecular-weight sulfated polysaccharide from the
      seaweed Laminaria japonica on glycerol-induced acute kidney injury in rats.
AB  - We investigated the renal protective effect of low-molecular-weight sulfated
      polysaccharide (LMWSP) fractions extracted from Laminaria japonica on glycerol
      induced acute kidney injury (AKI) in rats. Glycerol treatment significantly
      increased serum creatinine (SCr) and blood urea nitrogen (BUN) levels.
      Intraperitoneal injection of LMWSP fractions markedly decreased SCr and BUN
      levels and reduced renal swelling. The fraction of 1.0M NaCl displayed the best
      renal protective effect of all fractions in attenuating AKI and maintaining blood
      glucose.

PMID- 27865953
TI  - Polysaccharide of caper (Capparis spinosa L.) Leaf: Extraction optimization,
      antioxidant potential and antimicrobial activity.
AB  - Three-variable-three-level Box-Behnken design-response surface methodology (BBD
      RSM) based on the single-factor experiments was used to optimize the extracting
      parameters of crude polysaccharides (CPSs) from the Capparis spinosa leaves (CSL)
      including extraction time (ETi, 60-120min), extraction temperature (ETe, 60-80
      degrees C), and the water/solid ratio (W/S, 6-16). The optimal process conditions
      in order to the highest yield (6.73%) of CSL-CPSs were 119.8min ETi, 72.84
      degrees C ETe, and 15.97:1W/S.Structure of polysaccharide extracted at the
      optimal operating point were identified by Fourier transform-infrared
      spectroscopy (FT-IR). CSL-CPSs (50-300MUg/L) revealed significantly scavenging
      activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH)and OH free-radicals in
      vitro. A much more antimicrobial activity using this polysaccharide against Gram
      negative bacteria (Escherichia coli, Shigella dysenteriaeandSalmonella typhi) was
      found than Gram-positive bacteria (Bacillus panis and Staphylococcus aureus). CSL
      CPSs can thus be used as anexcellent antioxidant and antimicrobial ingredient in
      food and medicinal preparations.

PMID- 27865952
TI  - A superporous and superabsorbent glucuronoxylan hydrogel from quince (Cydonia
      oblanga): Stimuli responsive swelling, on-off switching and drug release.
AB  - Current study was designed to investigate micromeritic properties, water
      absorption capacity, stimuli (pH, ethanol and saline) responsive swelling
      deswelling (on-off switching) and controlled drug release from the polysaccharide
      glucuronoxylan isolated from the seeds of Quince. The water retention capacity of
      Quince hydrogel (QH) was found admirable. The hydrogel also exhibited privileged
      swelling in water and basic buffers (pH 6.8 and 7.4) while insignificant swelling
      in acidic buffer (pH 1.2). The swelling kinetics of QH follows second order.
      Moreover, QH deswells in salt (KCl and NaCl) solutions and ethanol. SEM of
      swollen then freeze dried QH revealed hollow channels with an average diameter of
      67.8MUm. Furthermore, QH sustained the release of levosulpiride (LS) tablet
      formulation and drug release mechanism was ascertained super case-II transport.
      These results signify QH a smart material for sustained release formulations.

PMID- 27865954
TI  - Laminating of chemically modified silan based nanosols for advanced
      functionalization of cotton textiles.
AB  - As per to silver nanoparticles/silicon dioxide nanoparticles (SiO2@AgNPs)
      properties (e.g., conductivity, reactant, adsorption, detachment and
      antimicrobial), many researchers were focused on its preparation technique. A
      core/shell of silicon dioxide and silver nanoparticles (SiO2@AgNPs) has been
      prepared by facile route. The as synthesized core/shell nanoparticles were
      chemically modified with two different silan compounds, nominated,
      vinyltriethoxysilan (VTEOS) and (3-aminopropyl)trimethoxysilan (APTEOS). World
      class facilities such as XRD, FT-IR, TEM, Particle size, DLS, SEM techniques were
      utilized for the nanoparticles characterization. The nanoparticulate system
      comprises SiO2@AgNPs, SiO2@AgNPs/APTEOS were applied to cotton fabric using
      butantetracarboxylic acid (BTCA) as across-linking agent. While UV irradiation by
      photo initiator was used as crosslinking agent for SiO2@AgNPs/VTEOS on cotton
      fabrics. The Treated cotton fabrics were evaluated for their surface morphology
      and heat transfer ability as well as antibacterial activity. The obtained data
      prove that the core/shell was successfully prepared, with AgNPs in core. In
      addition, both silan compounds (APTEOS, VTEOS) were successfully reacted with the
      outer shell SiO2. The results declared also that the treated fabrics exhibit a
      good antibacterial activity as well as good thermal properties.

PMID- 27865955
TI  - Studies to reveal the nature of interactions between catalase and curcumin using
      computational methods and optical techniques.
AB  - Curcumin is an important antioxidant compound, and is widely reported as an
      effective component for reducing complications of many diseases. However, the
      detailed mechanisms of its activity remain poorly understood. We found that
      curcumin can significantly increase catalase activity of BLC (bovine liver
      catalase). The mechanism of curcumin action was investigated using a
      computational method. We suggested that curcumin may activate BLC by modifying
      the bottleneck of its narrow channel. The molecular dynamic simulation data
      showed that placing curcumin on the structure of enzyme can increase the size of
      the bottleneck in the narrow channel of BLC, and readily allow the access of
      substrate to the active site. Because of the increase of the distance between
      amino acids of the bottleneck in the presence of curcumin, the entrance space of
      substrate increased from 250A3 to 440A3. In addition, the increase in emission of
      intrinsic fluorescence of BLC in presence of curcumin demonstrated changes in
      tertiary structure of catalase, and possibility of less quenching. We also used
      circular dichroism (CD) spectropolarimetry to determine how curcumin may alter
      the enzyme secondary structure. Catalase spectra in the presence of various
      concentrations of curcumin showed an increase in the amount of alpha-helix
      content.

PMID- 27865957
TI  - Starch functionalized biodegradable semi-IPN as a pH-tunable controlled release
      platform for memantine.
AB  - Sequentially prepared semi-interpenetrating polymer network (semi-IPN) has been
      developed here via Michael type addition of acrylic acid (AA) and 2-acrylamido-2
      methylpropane sulfonic acid (AMPS) on to starch. The semi-IPN hydrogel have
      proficiency in fast water imbibition towards gel network and swelling tunable
      character with pH alteration in ambient condition. The synthesized gel has been
      characterized by Fourier transformed infrared spectroscopy (FTIR) to confirm
      Michael type grafting of monomers on to starch. The surface morphology, observed
      from Scanning Electron Microscopy (SEM) exhibited corrugated rough surface on
      hydrogel which enhances the fast water uptake feature by anomalous Fickian case
      II diffusion mechanism. Grafting reaction also improves its thermal stability
      which has been confirmed by thermogravimetric analysis (TGA). Biodegradation
      study with hen egg lysozyme medium reveals the accelerated enzymatic scission of
      the starch backbone and progressive mass loss. Degradation of the hydrogel around
      60% of its primary mass has been observed within 7days. The physicochemical
      characterizations of this hydrogel suggest this as a promising pH-tunable,
      biodegradable candidate for control drug delivery vehicle.

PMID- 27865956
TI  - Safranal and its analogs inhibit Escherichia coli ATP synthase and cell growth.
AB  - Safranal, a dominant component of saffron, is known to have antitumor, cytotoxic,
      and antibacterial properties. In this study, we examined safranal and its
      structural analogs-thymol, carvacrol, damascenone, cuminol, 2,6,6-trimethyl-2
      cyclohexene-1,4-dione (TMCHD), 4-isopropylbenzyl bromide (IPBB), and 4-tert
      butylphenol (TBP) induced inhibition of Escherichia coli membrane bound F1Fo ATP
      synthase. Safranal and its analogs inhibited wild-type enzyme to variable
      degrees. While safranal caused 100% inhibition of wild-type F1Fo ATP synthase,
      only about 50% inhibition occurred for alphaR283D mutant ATP synthase. Moreover,
      safranal, thymol, carvacrol, damascenone, cuminol, TMCHD, IPBB, and TBP all fully
      abrogated the growth of wild-type E. coli cells and had partial or no effect on
      the growth of null and mutant E. coli strains. Therefore, the antimicrobial
      properties of safranal, thymol, carvacrol, damascenone, cuminol, TMCHD, IPBB, and
      TBP can be linked to their binding and inhibition of ATP synthase. Total loss of
      growth in wild-type and partial or no growth loss in null or mutant E. coli
      strains demonstrates that ATP synthase is a molecular target for safranal and its
      structural analogs. Partial inhibition of the alphaArg-283 mutant enzyme
      establishes that alphaArg-283 residue is required in the polyphenol binding
      pocket of ATP synthase for the binding of safranal. Furthermore, partial growth
      loss for the null and mutant strains in the presence of inhibitors also suggests
      the role of other targets and residues in the process of inhibition.

PMID- 27865958
TI  - Development of bone-like zirconium oxide nanoceramic modified chitosan based
      porous nanocomposites for biomedical application.
AB  - Here, zirconium oxide nanoparticles (ZrO2 NPs) were incorporated for the first
      time in organic-inorganic hybrid composites containing chitosan, poly(ethylene
      glycol) and nano-hydroxypatite (CS-PEG-HA) to develop bone-like nanocomposites
      for bone tissue engineering application. These nanocomposites were characterized
      by FT-IR, XRD, TEM combined with SAED. SEM images and porosity measurements
      revealed highly porous structure having pore size of less than 1MUm to 10MUm.
      Enhanced water absorption capacity and mechanical strengths were obtained
      compared to previously reported CS-PEG-HA composite after addition of 0.1-0.3wt%
      of ZrO2 NPs into these nanocomposites. The mechanical strengths and porosities
      were similar to that of human spongy bone. Strong antimicrobial effects against
      gram-negative and gram-positive bacterial strains were also observed. Along with
      getting low alkalinity pH (7.4) values, similar to the pH of human plasma,
      hemocompatibility and cytocompatibility with osteoblastic MG-63 cells were also
      established for these nanocomposites. Addition of 15wt% HA-ZrO2 (having 0.3wt%
      ZrO2 NPs) into CS-PEG (55:30wt%) composite resulted in greatest mechanical
      strength, porosity, antimicrobial property and cytocompatibility along with
      suitable water absorption capacity and compatibility with human pH and blood.
      Thus, this nanocomposite could serve as a potential candidate to be used for bone
      tissue engineering.

PMID- 27865959
TI  - Ultrasensitive cardiac troponin I antibody based nanohybrid sensor for rapid
      detection of human heart attack.
AB  - An ultrasensitive cardiac troponin I antibody conjugated with graphene quantum
      dots (GQD) and polyamidoamine (PAMAM) nanohybrid modified gold electrode based
      sensor was developed for the rapid detection of heart attack (myocardial
      infarction) in human. Screen printed gold (Au) electrode was decorated with 4
      aminothiophenol for amine functionalization of the Au surface. These amino groups
      were further coupled with carboxyl functionalities of GQD with EDC-NHS reaction.
      In order to enhance the sensitivity of the sensor, PAMAM dendrimer was
      successively embedded on GQD through carbodiimide coupling to provide ultra-high
      surface area for antibody immobilization. The activated cardiac troponin I (cTnI)
      monoclonal antibody was immobilized on PAMAM to form nanoprobe for sensing
      specific heart attack marker cTnI. Various concentrations of cardiac marker, cTnI
      were electrochemically measured using cyclic voltammetry (CV) and differential
      pulse voltammetry (DPV) in human blood serum. The modifications on sensor surface
      were characterized by FTIR and AFM techniques. The sensor is highly specific to
      cTnI and showed negligible response to non-specific antigens. The sensitivity of
      the sensor was 109.23MUAcm-2MUg-1 and lower limit of detection of cTnI was found
      20fgmL-1.

PMID- 27865960
TI  - Identification of Inonotus obliquus polysaccharide with broad-spectrum antiviral
      activity against multi-feline viruses.
AB  - Inonotus obliquus polysaccharides (IOPs) are a potential drug for the prevention
      and treatment of cancer, cardiopathy, diabetes, AIDs, pancreatitis and other
      diseases. In this study, we found that IOP can act as a broad-spectrum antiviral
      drug against feline viruses in the in vitro experiment. Using cell models of
      feline calicivirus (FCV), we demonstrated that IOP treatment was capable of
      exhibiting anti-FCV strain F9 activity in cell-based assays and also showed low
      cytotoxicity. Investigation of the mechanism of action of the compound revealed
      that IOP treatment induces its inhibitory actions directly on virus particles
      through blocking viral binding/absorpting. The inhibitory activity against other
      FCV isolates from China was also identified. More importantly, we found that IOP
      exhibited broad-spectrum antiviral activity against the feline herpesvirus 1,
      feline influenza virus H3N2 and H5N6, feline panleukopenia virus and feline
      infectious peritonitis virus that can contribute to respiratory and
      gastrointestinal diseases in cats. These findings suggest that IOP may be a
      potential broad-spectrum antiviral drug against feline viruses.

PMID- 27865961
TI  - Lifetime depression and anxiety increase prevalent psychological symptoms and
      worsen glycemic control in type 2 diabetes: The Fremantle Diabetes Study Phase
      II.
AB  - AIMS: To determine the contribution of lifetime major depressive disorder (L-MDD)
      and lifetime generalized anxiety disorder (L-GAD) to current psychological
      symptom severity, health behaviour and glycaemic control in type 2 diabetes.
      METHODS: 1285 community-dwelling people with type 2 diabetes (Fremantle Diabetes
      Study Phase-II; FDS2) completed the PHQ-9 and Brief Life-Time Depression Scale
      (BLDS) to assess current and past MDD. The Generalized Anxiety Disorder Scale
      (GADS) and the Generalized Anxiety Disorder Scale-Lifetime (GAD-LT), designed for
      FDS2, assessed current and past anxiety. Data were analysed using analysis of
      covariance and multiple mediation models, controlling for age, gender, marital
      status, and diabetes duration. RESULTS: L-MDD and L-GAD were independently
      associated with more severe current depression (both P<0.001) and anxiety (both
      P<0.001) symptoms. Mediation models revealed that, through increasing the
      severity of current depressive symptoms, L-MDD was associated with higher HbA1c
      and body mass index (BMI), greater likelihood of current smoking, and reduced
      self-monitoring of blood glucose (SMBG) (indirect regression path ab, all
      P<0.001). In combination, L-MDD+L-GAD additionally elevated the risk of higher
      HbA1c and worse diabetes management, by increasing the severity of current
      depressive symptoms (indirect regression path ab, all P<0.001). CONCLUSIONS:
      Lifetime depression and anxiety increase risk of more severe psychological
      symptoms, hyperglycaemia, and difficulties with health behaviour in type 2
      diabetes. Early screening for these disorders at diabetes diagnosis may be
      warranted to maximize long-term health outcomes.

PMID- 27865963
TI  - Improved vascularization of porous scaffolds through growth factor delivery from
      heparinized polyethylene glycol hydrogels.
AB  - : Surface modification with heparin has previously been shown to increase
      vascularization of porous scaffolds. In order to determine its efficacy with
      sustained release, heparin (Hep) was covalently incorporated into degradable
      (Type D) and non-degradable (Type N) polyethylene glycol (PEG) hydrogels. After
      in vitro characterization of their physicochemical properties, growth factor (GF)
      loaded, heparinised Type D gels were formed within the pores of porous
      polyurethane disks, which were then implanted and evaluated in a subcutaneous
      model. Type N gels formed faster (3.1+/-0.1 vs. 7.2+/-0.2min), were stiffer
      (10.0+/-0.5kPa vs. 7.1+/-1.2kPa) and more stable than degradable gels (>6month
      stability vs. disintegration ?22d in vitro; all p<0.001). Sustained release of
      covalently incorporated (CI) heparin from Type N (56days; first order kinetics)
      and Type D (21days; zero order kinetics) was achieved, as opposed to non
      covalently incorporated (NI) heparin that eluted in a burst release within the
      first 2days. While Type D gels initially impeded tissue ingrowth into the porous
      scaffolds, they were completely degraded and replaced by ingrown tissue after
      28days in vivo. At the latter timepoint disks containing gels without Hep or with
      non-covalently incorporated Hep were less vascularized than empty (no gel)
      controls. In contrast, the incorporation of covalently heparinized (no GF) and GF
      containing gels (no Hep) resulted in a 50% and 42% (p<0.05) improvement in
      vascularization, while an increase of 119% (p<0.001) was achieved with a
      combination of covalently attached Hep and GF. These gels thus provide a
      sustained release system for heparin and GF that extends the duration of their
      action to local tissue ingrowth. STATEMENT OF SIGNIFICANCE: The paper describes
      the modification and covalent incorporation of heparin into degradable and non
      degradable polyethylene glycol hydrogels in a way that provides for the
      hydrolytic cleavage of the linker for the release of the heparin in original and
      active form, and in an extended (21-56d) controlled (zero and first order
      respectively) manner. The successful use of these gels as growth-factor
      containing and releasing matrices for the improvement of in vivo vascularization
      holds promise for many potential uses in tissue engineering and regenerative
      medicine applications, such as vascular grafts and myocardial infarction therapy,
      where the antithrombotic and/or growth factor binding/potentiating properties are
      required.

PMID- 27865962
TI  - Pharmacologically active microcarriers delivering BDNF within a hydrogel: Novel
      strategy for human bone marrow-derived stem cells neural/neuronal differentiation
      guidance and therapeutic secretome enhancement.
AB  - : Stem cells combined with biodegradable injectable scaffolds releasing growth
      factors hold great promises in regenerative medicine, particularly in the
      treatment of neurological disorders. We here integrated human marrow-isolated
      adult multilineage-inducible (MIAMI) stem cells and pharmacologically active
      microcarriers (PAMs) into an injectable non-toxic silanized-hydroxypropyl
      methylcellulose (Si-HPMC) hydrogel. The goal is to obtain an injectable non-toxic
      cell and growth factor delivery device. It should direct the survival and/or
      neuronal differentiation of the grafted cells, to safely transplant them in the
      central nervous system, and enhance their tissue repair properties. A model
      protein was used to optimize the nanoprecipitation conditions of the
      neuroprotective brain-derived neurotrophic factor (BDNF). BDNF nanoprecipitate
      was encapsulated in fibronectin-coated (FN) PAMs and the in vitro release profile
      evaluated. It showed a prolonged, bi-phasic, release of bioactive BDNF, without
      burst effect. We demonstrated that PAMs and the Si-HPMC hydrogel increased the
      expression of neural/neuronal differentiation markers of MIAMI cells after 1week.
      Moreover, the 3D environment (PAMs or hydrogel) increased MIAMI cells secretion
      of growth factors (b-NGF, SCF, HGF, LIF, PlGF-1, SDF-1alpha, VEGF-A & D) and
      chemokines (MIP-1alpha & beta, RANTES, IL-8). These results show that PAMs
      delivering BDNF combined with Si-HPMC hydrogel represent a useful novel local
      delivery tool in the context of neurological disorders. It not only provides
      neuroprotective BDNF but also bone marrow-derived stem cells that benefit from
      that environment by displaying neural commitment and an improved
      neuroprotective/reparative secretome. It provides preliminary evidence of a
      promising pro-angiogenic, neuroprotective and axonal growth-promoting device for
      the nervous system. STATEMENT OF SIGNIFICANCE: Combinatorial tissue engineering
      strategies for the central nervous system are scarce. We developed and
      characterized a novel injectable non-toxic stem cell and protein delivery system
      providing regenerative cues for central nervous system disorders. BDNF, a
      neurotrophic factor with a wide-range effect, was nanoprecipitated to maintain
      its structure and released in a sustained manner from novel polymeric
      microcarriers. The combinatorial 3D support, provided by fibronectin
      microcarriers and the hydrogel, to the mesenchymal stem cells guided the cells
      towards a neuronal differentiation and enhanced their tissue repair properties by
      promoting growth factors and cytokine secretion. The long-term release of
      physiological doses of bioactive BDNF, combined to the enhanced secretion of
      tissue repair factors from the stem cells, constitute a promising therapeutic
      approach.

PMID- 27865964
TI  - Array-based functional peptide screening and characterization of gold
      nanoparticle synthesis.
AB  - : Based on inorganic material production through biomineralization in organisms,
      the use of biological molecules in nanomaterial production has received
      increasing attention as a vehicle to synthesize inorganic materials with selected
      properties in ambient conditions. Among various biological molecules that
      interact with metallic surfaces, short peptides are putative ligand molecules as
      they exhibit potential to control the synthesis of nanoscale materials with
      tailored functions. Herein, using a spot synthesis-based peptide array, the gold
      nanoparticle (AuNP) binding activities of approximately 1800 peptides were
      evaluated and revealed various activities ranging from positive (high-affinity
      binding peptides) to negative (weak- or null-affinity binding peptides). Among 50
      peptides showing the highest AuNP binding activity, 46 sequences showed the
      presence of tryptophan-based motifs including W[Xn]W, H[Xn]W, and W[Xn]H (W:
      tryptophan, X: any amino acid, n: 1-8 amino acid residues), whereas none of these
      motifs was found in the WORST50 peptides. Notably, three peptides showing the
      highest binding affinities possessed bi-functionality in AuNP binding and Au(III)
      reduction in solution and on solid surfaces. In addition, the characterization of
      truncated peptide derivatives revealed unique peptide motifs for their function
      expressions that also supported the importance of tryptophan-based motifs for
      peptide-AuNP binding. These findings open the door for peptide-mediated precise
      regulation of AuNP synthesis in ambient condition and for site dependent
      controlled AuNP integration onto nanotechnological devices. STATEMENT OF
      SIGNIFICANCE: The development of a technique for functionally regulated nanosized
      material production in ambient condition is broadly required according to the
      expansion of nanomaterial based applications. Short peptides, which bind to
      metallic surfaces, have great potential for the technique development, but the
      realization remains a difficult challenge due to the lack of metal binding
      peptide varieties. Herein, approximately 1800 peptides with the gold nanoparticle
      (AuNP) binding activity are reported and characterized. Furthermore, by three
      highest binding peptides, the expression of bi-functionality in AuNP binding and
      Au(III) reduction was serendipitously discovered in solution and on solid
      surfaces. These findings will be attributed to new technique development of
      functional nanoparticle synthesis in mild condition, and for site-dependent AuNP
      integration in various nanotechnological devices.

PMID- 27865965
TI  - Palladin is involved in platelet activation and arterial thrombosis.
AB  - The dynamics of actin cytoskeleton have been shown to play a critical role during
      platelet activation. Palladin is an actin-associated protein, serving as a
      cytoskeleton scaffold to bundle actin fibers and actin cross linker. The
      functional role of palladin on platelet activation has not been investigated.
      Here, we characterized heterozygous palladin knockout (palladin+/-) mice to
      elucidate the platelet-related functions of palladin. The results showed that
      palladin was expressed in platelets and moderate palladin deficiency accelerated
      hemostasis and arterial thrombosis. The aggregation of palladin+/- platelets was
      increased in response to low levels of thrombin, U46619, and collagen. We also
      observed enhanced spreading of palladin+/- platelets on immobilized fibrinogen
      (Fg) and increased rate of clot retraction in platelet-rich plasma (PRP)
      containing palladin+/- platelets. Furthermore, the activation of the small GTPase
      Rac1 and Cdc42, which is associated with cytoskeletal dynamics and platelet
      activation signalings, was increased in the spreading and aggregating palladin+/-
      platelets compared to that in wild type platelets. Taken together, these findings
      indicated that palladin is involved in platelet activation and arterial
      thrombosis, implying a potent role of palladin in pathophysiology of thrombotic
      diseases.

PMID- 27865966
TI  - Febuxostat attenuates paroxysmal atrial fibrillation-induced regional endothelial
      dysfunction.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (PAF) can increase thrombogenesis
      risk, especially in the left atrium (LA). The exact mechanism is still unclear.
      OBJECTIVE: We assessed the effects of PAF on endothelial function, and
      investigated if febuxostat (FX) can attenuate endothelial dysfunction by
      inhibition of xanthine oxidase (XO). MATERIALS AND METHODS: Eighteen male New
      Zealand white rabbits were divided randomly into sham-operated (S), PAF (P) or
      FX+pacing (FP) groups. Group P and group FP received rapid atrial pacing (RAP).
      Group FP was administered febuxostat (FX) for 7days before RAP. Post-procedure,
      blood samples were collected from the LA, right atrium (RA) and peripheral
      circulation. Tissues from the LA and RA were obtained. Endothelial dysfunction
      (thrombomodulin [TM], von Willebrand factor [VWF], asymmetric dimethylarginine
      [ADMA]), and indirect thrombin generation (thrombin-antithrombin complex [TAT],
      prothrombin fragment 1+2 [F1.2]) and oxidative stress in atrial tissue (xanthine
      oxidase [XO], superoxide dismutase [SOD], malondialdehyde [MDA]) were measured
      using an Enzyme-linked immunosorbent assay. Atrial endothelial expression of TM
      and VWF was measured by histology/western blotting. RESULTS AND CONCLUSIONS:
      Endothelial dysfunction (TM, VWF, ADMA), TAT generation and oxidative stress (XO,
      SOD, MDA) in group P were more significant compared with that in group S (p<0.05,
      respectively). In group P, all of these changes occurred to a greater extent in
      the LA compared with those in the RA or peripheral circulation. In group FP, FX
      attenuated endothelial dysfunction and reduced TAT levels by inhibition of XO
      mediated oxidative stress. PAF can lead to endothelial dysfunction and TAT
      generation by XO-mediated oxidative stress. The LA is more susceptible to these
      effects. FX can attenuate these changes by inhibition XO and XO-mediated
      oxidative stress.

PMID- 27865967
TI  - Usual and unusual mutations in a cohort of Belgian patients with hemophilia B.

PMID- 27865968
TI  - The dorsomedial prefrontal cortex plays a causal role in mediating in-group
      advantage in emotion recognition: A TMS study.
AB  - Consistent evidence suggests that emotional facial expressions are better
      recognized when the expresser and the perceiver belong to the same social group
      (in-group advantage). In this study, we used transcranial magnetic stimulation
      (TMS) to investigate the possible causal involvement of the dorsomedial
      prefrontal cortex (dmPFC) and of the right temporo-parietal junction (TPJ), two
      main nodes of the mentalizing neural network, in mediating the in-group advantage
      in emotion recognition. Participants performed an emotion discrimination task in
      a minimal (blue/green) group paradigm. We found that interfering with activity in
      the dmPFC significantly interfered with the effect of minimal group-membership on
      emotion recognition, reducing participants' ability to discriminate emotions
      expressed by in-group members. In turn, rTPJ mainly affected emotion
      discrimination per se, irrespective of group membership. Overall, our results
      point to a causal role of the dmPFC in mediating the in-group advantage in
      emotion recognition, favoring intragroup communication.

PMID- 27865969
TI  - Age-related alterations in functional connectivity patterns during working memory
      encoding of emotional items.
AB  - Previous findings indicate age-related differences in frontal-amygdala
      connectivity during emotional processing. However, direct evidence for age
      differences in brain functional activation and connectivity during emotional
      processing and concomitant behavioral implications is lacking. In the present
      study, we examined the impact of aging on the neural signature of selective
      attention to emotional information during working memory (WM) encoding.
      Participants completed an emotional WM task in which they were asked to attend to
      emotional targets and ignore irrelevant distractors. Despite an overall reduction
      in accuracy for older relative to younger adults, no behavioral age effect was
      observed as a function of emotional valence. The functional connectivity patterns
      of left ventrolateral prefrontal cortex showed that younger adults recruited one
      network for encoding of both positive and negative emotional targets and this
      network contributed to higher memory accuracy in this cohort. Older adults, on
      the other hand, engaged two distinct networks for encoding of positive and
      negative targets. The functional connectivity analysis using left amygdala
      further demonstrated that older adults recruited one single network during
      encoding of positive as well as negative targets whereas younger adults recruited
      this network only for encoding of negative items. The engagement of amygdala
      functional network also contributed to higher memory performance and faster
      response times in older adults. Our findings provide novel insights into the
      differential roles of functional brain networks connected to the medial PFC and
      amygdala during encoding of emotionally-valenced items with advancing age.

PMID- 27865970
TI  - Insights into amyloid-like aggregation of H2 region of the C-terminal domain of
      nucleophosmin.
AB  - Nucleophosmin (NPM1) is a multifunctional protein involved in a variety of
      biological processes including the pathogenesis of several human malignancies and
      is the most frequently mutated gene in Acute Myeloid Leukemia (AML). To deepen
      the role of protein regions in its biological activities, lately we reported on
      the structural behavior of dissected C-terminal domain (CTD) helical fragments.
      Unexpectedly the H2 (residues 264-277) and H3 AML-mutated regions showed a
      remarkable tendency to form amyloid-like assemblies with fibrillar morphology and
      beta-sheet structure that resulted as toxic when exposed to human neuroblastoma
      cells. More recently NPM1 was found to be highly expressed and toxic in neurons
      of mouse models of Huntington's disease (HD). Here we investigate the role of
      each residue in the beta-strand aggregation process of H2 region of NPM1 by
      performing a systematic alanine scan of its sequence and structural and kinetic
      analyses of aggregation of derived peptides by means of Circular Dichorism (CD)
      and Thioflavin T (Th-T) assay. These solution state investigations pointed out
      the crucial role exerted by the basic amyloidogenic stretch of H2 (264-271) and
      to shed light on the initial and main interactions involved in fibril formation
      we performed studies on fibrils deriving from the related Ala peptides through
      the analysis of fibrils with birefringence of polarized optical microscopy and
      wide-angle X-ray scattering (WAXS). This analysis suggested that the presence of
      branched Ile269 conferred preferential packing patterns that, instead, appeared
      geometrically hampered by the aromatic side-chain of Phe268. Present
      investigations could be useful to deepen the knowledge of AML molecular
      mechanisms and the role of cytoplasmatic aggregates of NPM1c+.

PMID- 27865971
TI  - Complete genome sequence of a non-pathogenic strain of Fowl Adenovirus serotype
      11: Minimal genomic differences between pathogenic and non-pathogenic viruses.
AB  - In this study, we conducted the clinicopathological characterization of a non
      pathogenic FAdV-D serotype 11 strain MX95, isolated from healthy chickens, and
      its entire genome was sequenced. Experiments in SPF chickens revealed that the
      strain is a non-pathogenic virus that did not cause death at challenge doses of
      1*106 TCID50. Additionally, the infection in SPF chickens caused no apparent
      damage in most of the organs analyzed by necropsy and histopathology, but it did
      cause inclusion body hepatitis; nevertheless it did not generate severe
      infectious clinical symptoms. The virus was detected in several chicken organs,
      including the lymphoid organs, by real-time polymerase chain reaction (PCR) until
      42 days. The genome of FAdV-11 MX95 has a size of 44,326bp, and it encodes 36
      open reading frames (ORFs). Comparative analysis of the genome indicated only
      0.8% dissimilarity with a highly virulent serotype 11 that was previously
      reported.

PMID- 27865972
TI  - Paediatric urolithiasis in emerging economies.
AB  - BACKGROUND: Paediatric urolithiasis remains endemic in low resource countries.
      This review highlights the epidemiology, causation and management of urolithiasis
      in an Asian country in the context of emerging economies. METHODS: A literature
      review of recent articles with key words paediatric urolithiasis, developing
      countries, endemic stone disease, stone composition, metabolic risk factors,
      management of paediatric urolithiasis was undertaken and 51 relevant articles
      were selected with the main focus on experience of this center in managing stone
      disease in the last two decades. RESULTS: Prevalence of paediatric urolithiasis
      is high upto 15% affecting children under 15 years with male predominance.
      Bladder stones still constitutes 10-70% of the burden. Etiology remains unknown
      where 55% are considered idiopathic, 25% metabolic, 7% infection and 12% due to
      anatomical abnormalities. Hot climate, poor nutrition, diarrheal diseases are the
      major causative factors. Chemical composition of stones showed CaOX in 30-63%,
      AAU in 17-55%, struvite in 8-9%, uric acid in 3-6% and cystine in 1%. Important
      metabolic risk factors are hypocitraturia in 63-87%, hyperoxaluria in 40-43%,
      hypocalciuria in 20%, hyperuricosuria in 27%, hyperammonuria in 11-51% and
      hypovolemia in 31%. Minimally invasive surgery is the mainstay of surgical
      management. ESWL provides excellent free rates of 84% for smaller stones. PCNL is
      the option for majority of renal stones with success rates of 89% for simple and
      71.5% for complex stones. For bladder stones PUCL and PCCL success rates were
      100%. URS for ureteric stones showed clearance rate of 90%. Open surgery is
      required in 12% of patients with large stone burden. CONCLUSION: Paediatric
      urolithiasis remains a devastating health problem in low resource settings. MIS
      offers relief to majority of patients with excellent stone free rates and short
      hospital stay. Preventable strategies have to be put in place by improving
      nutrition and eliminating risk factors by diet and medical intervention.

PMID- 27865973
TI  - Hypertension and other cardiovascular risk factors are associated with vitamin D
      deficiency in an urban Chinese population: A short report.
AB  - There is debate concerning the association of 25-hydroxyvitamin D (25OHD) and
      parathyroid hormone (PTH) with cardiovascular disease (CVD) risk factors. As both
      hypertension and vitamin D deficiency are increasingly important public health
      concerns in China, we investigated these associations in 566 Macao residents. The
      aim was to investigate the association of serum 25OHD and PTH concentrations with
      CVD risk factors (hypertension, high pulse rate, abnormal blood lipids). The data
      were stratified by age, sex, and blood pressure (BP) medication use. Multiple
      linear regression analyses were performed to assess associations, adjusting for
      appropriate confounders. Lower 25OHD concentrations were significantly associated
      with higher systolic BP (SBP) mmHg (beta=-0.07), diastolic BP (DBP) mmHg (beta=
      0.06) and pulse rate beats/min (beta=-0.12), lower high-density lipoprotein (HDL)
      concentrations nmol/L (beta=10.51) and higher triglycerides (TG) nmol/L (beta=
      2.38). However, the inverse associations with lower 25OHD for higher SBP, DBP,
      pulse rate and TG were much stronger in those using BP medications, in those who
      were older, and in females. Higher PTH concentrations were significantly
      associated with higher low-density lipoprotein (LDL) nmol/L (beta=0.77) in the
      total population and with higher SBP mmHg (beta=0.08) in males and those who were
      older (beta=0.09). In conclusion, our major new finding is that lower 25OHD is
      associated with higher BP especially in those who use BP medications. These
      results might explain past discrepancies in findings regarding the association of
      BP and vitamin D and suggest that prospective studies and randomized control
      trials, in otherwise healthy Chinese populations taking blood pressure
      medications, are needed to confirm these cross-sectional results.

PMID- 27865974
TI  - Importance of the combined urinary procedure for the diagnosis of
      Mucopolysaccharidoses.
AB  - BACKGROUND: Mucopolysaccharidoses are characterized by the accumulation of
      undegraded glycosaminoglycans in lysosomes in multiple organs and by their
      excretion in high amounts in urine. The aim of this study is to determine if this
      simple, reliable and reproducible method is useful for the diagnosis of
      Mucopolysaccharidoses. METHODS: The study included 2154 normal urine samples and
      210 samples from 73 patients affected by different types of
      Mucopolysaccharidoses. The glycosaminoglycans were quantified by a
      dimethylmethylene blue method and size-fractionated by a modified one-dimensional
      electrophoresis method. RESULTS: The combination of the two methods allowed to
      identify all the patients affected by the different types of
      Mucopolysaccharidosis with 100% sensitivity and specificity. CONCLUSION: This
      combined approach gives fast diagnostic orientation about the different types of
      Mucopolysaccharidoses, offering an important tool for a better understanding of
      diagnosis and patient management.

PMID- 27865976
TI  - Comment on treatment for recurrent vulvovaginal candidiasis.

PMID- 27865975
TI  - Differences in placental telomere length suggest a link between racial
      disparities in birth outcomes and cellular aging.
AB  - BACKGROUND: Health disparities begin early in life and persist across the life
      course. Despite current efforts, black women exhibit greater risk for pregnancy
      complications and negative perinatal outcomes compared with white women. The
      placenta, which is a complex multi-tissue organ, serves as the primary transducer
      of bidirectional information between the mother and fetus. Altered placental
      function is linked to multiple racially disparate pregnancy complications;
      however, little is known about racial differences in molecular factors within the
      placenta. Several pregnancy complications, which include preeclampsia and fetal
      growth restriction, exhibit racial disparities and are associated with shorter
      placental telomere length, which is an indicator of cellular stress and aging.
      Cellular senescence and telomere dynamics are linked to the molecular mechanisms
      that are associated with the onset of labor and parturition. Further, racial
      differences in telomere length are found in a range of different peripheral
      tissues. Together these factors suggest that exploration of racial differences in
      telomere length of the placenta may provide novel mechanistic insight into racial
      disparities in birth outcomes. OBJECTIVE: This study examined whether telomere
      length measured in 4 distinct fetally derived tissues were significantly
      different between black and white women. The study had 2 hypotheses: (1) that
      telomere length that is measured in different placental tissue types would be
      correlated and (2) that across all sampled tissues telomere length would differ
      by race. STUDY DESIGN: In a prospective study, placental tissue samples were
      collected from the amnion, chorion, villus, and umbilical cord from black and
      white singleton pregnancies (N=46). Telomere length was determined with the use
      of monochrome multiplex quantitative real-time polymerase chain reaction in each
      placental tissue. Demographic and pregnancy-related data were also collected.
      Descriptive statistics characterized the sample overall and among black and white
      women separately. The overall impact of race was assessed by multilevel mixed
      effects linear regression models that included empirically relevant covariates.
      RESULTS: Telomere length was correlated significantly across all placental
      tissues. Pairwise analyses of placental tissue telomere length revealed
      significantly longer telomere length in the amnion compared with the chorion (t=
      2.06; P=.043). Overall telomere length measured in placenta samples from black
      mothers were significantly shorter than those from white mothers (beta=-0.09;
      P=.04). Controlling for relevant maternal and infant characteristics strengthened
      the significance of the observed racial differences (beta=-0.12; P=.02). Within
      tissue analyses revealed that the greatest difference by race was found in
      chorionic telomere length (t=-2.81; P=.007). CONCLUSION: These findings provide
      the first evidence of racial differences in placental telomere length. Telomere
      length was significantly shorter in placental samples from black mothers compared
      with white mothers. Given previous studies that have reported that telomere
      length, cellular senescence, and telomere dynamics are molecular factors that
      contribute to the rupture of the amniotic sac, onset of labor, and parturition,
      our findings of shorter telomere length in placentas from black mothers suggest
      that accelerated cellular aging across placental tissues may be relevant to the
      increased risk of preterm delivery in black pregnancies. Our results suggest that
      racial differences in cellular aging in the placenta contribute to the earliest
      roots of health disparities.

PMID- 27865977
TI  - Racial/ethnic differences in preterm perinatal outcomes.
AB  - BACKGROUND: Racial disparities in preterm birth and infant death have been well
      documented. Less is known about racial disparities in neonatal morbidities among
      infants who are born at <37 weeks of gestation. OBJECTIVE: The purpose of this
      study was to determine whether the risk for morbidity and death among infants who
      are born preterm differs by maternal race. STUDY DESIGN: A retrospective cohort
      design included medical records from preterm deliveries of 19,325 black,
      Hispanic, and white women in the Consortium on Safe Labor. Sequentially adjusted
      Poisson models with generalized estimating equations estimated racial differences
      in the risk for neonatal morbidities and death, controlling for maternal
      demographics, health behaviors, and medical history. Sex differences between and
      within race were examined. RESULTS: Black preterm infants had an elevated risk
      for perinatal death, but there was no difference in risk for neonatal death
      across racial groups. Relative to white infants, black infants were significantly
      more likely to experience sepsis (9.1% vs 13.6%), peri- or intraventricular
      hemorrhage (2.6% vs 3.3%), intracranial hemorrhage (0.6% vs 1.8%), and
      retinopathy of prematurity (1.0% vs 2.6%). Hispanic and white preterm neonates
      had similar risk profiles. In general, female infants had lower risk relative to
      male infants, with white female infants having the lowest prevalence of a
      composite indicator of perinatal death or any morbidity across all races (30.9%).
      Differences in maternal demographics, health behaviors, and medical history did
      little to influence these associations, which were robust to sensitivity analyses
      of pregnancy complications as potential underlying mechanisms. CONCLUSION:
      Preterm infants were at similar risk for neonatal death, regardless of race;
      however, there were notable racial disparities and sex differences in rare, but
      serious, adverse neonatal morbidities.

PMID- 27865978
TI  - Reply.

PMID- 27865979
TI  - Characterizing women with interest in uterine transplant clinical trials in the
      United States: who seeks information on this experimental treatment?

PMID- 27865981
TI  - SRB1 as a new redox target of cigarette smoke in human sebocytes.
AB  - For its critical location, the skin represents the major interface between the
      body and the environment, therefore is one of the major biological barriers
      against the outdoor environmental stressors. Among the several oxidative
      environmental stressors, cigarette smoke (CS) has been associated with the
      development and worsening of many skin pathologies such as acne, dermatitis,
      delayed wound healing, aging and skin cancer. In our previous work we have
      demonstrated that CS is able to affect genes involved in skin cholesterol
      trafficking, among which SRB1, a receptor involved in the uptake of cholesterol
      from HDL, seems to be very susceptible to the oxidative stress induced by CS. In
      the present work we wanted to investigate the presence of SRB1 in human sebocytes
      and whether CS can affect cholesterol cellular uptake via the redox modulation of
      SRB1. By using a co-culture system of keratinocytes/sebocytes, we found that CS
      exposure induced a SRB1 protein loss without affecting sebocytes viability. The
      decrease of SRB1 levels was a consequence of SRB1/HNE adducts formation that
      leads to SRB1 ubiquitination and degradation. Moreover, the CS-induced loss of
      SRB1 induced an alteration of sebocytes lipid content, also demonstrated by
      cholesterol quantification in SRB1 siRNA experiments. In conclusion, exposure to
      CS, induced SRB1 post-translational modifications in sebocytes and this might
      affect sebocytes/skin functionality.

PMID- 27865983
TI  - Transdermal therapeutic systems for memantine delivery. Comparison of passive and
      iontophoretic transport.
AB  - Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist
      used in the treatment of moderate to severe dementia including the symptoms of
      Alzheimer's disease (AD). It is administered orally but compliance, swallowing
      problems and the routine use of multiple medications in elderly AD patients means
      that an alternative route of administration would be of interest. The aim of the
      present study was to develop memantine hydrochloride occlusive transdermal
      therapeutic systems (TTS) for passive and iontophoretic delivery across the skin.
      Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were
      employed as polymeric matrices. The study involved the TTS characterization in
      addition to quantification of the memantine transport across porcine skin in
      vitro. The evaluation of the TTS physical properties suggested that systems were
      made more mechanically resistant by including PVA (6%) or high concentrations of
      PVP (24%). Moreover, a linear correlation was observed between the concentration
      of PVP and the bioadhesion of the systems. Drug delivery experiments showed that
      the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was
      8.89+/-0.81MUgcm-2h-1 whereas the highest iontophoretic transport was 46.4+/
      3.6MUgcm-2h-1. These innovative TTS would enable two dosage regimens that could
      lead to therapeutic plasma concentrations.

PMID- 27865986
TI  - Persistence of antimicrobial resistance in respiratory streptococci.
AB  - OBJECTIVES: To assess whether persistence of antimicrobial resistance (i.e. non
      susceptible resistance status) after treatment with penicillins or cephalosporins
      versus macrolides or tetracyclines differs and to compare the results obtained
      using routinely collected data with findings reported in prospective studies.
      METHODS: Routinely collected microbiological data from 14 voluntary participating
      laboratories (2005) containing information on resistance status and individual
      antimicrobial consumption patterns (mid 2004-2005) were analysed using a
      generalised estimating equation (GEE) approach. The link function was adjusted to
      acknowledge that the proportion of resistant isolates in the population not
      treated with antibiotics [baseline resistance (BR)] is not necessarily zero. To
      optimise the comparability of this study with prospective studies, the analysis
      was repeated after removal of 14 isolates from patients who did not survive 2005.
      RESULTS: BR estimates were unstable and their confidence intervals were wide,
      which called for a sensitivity analysis using an adjusted GEE model with three
      different BR estimates. All models indicated that the proportion of susceptible
      isolates differed by treatment group and increased significantly over time, with
      this increase being independent of treatment group. Persistence of resistance
      after exposure to macrolides or tetracyclines was approximately three times as
      long as after exposure to penicillins or cephalosporins. CONCLUSIONS: Resistance
      following treatment with macrolides or tetracyclines persists longer than
      following treatment with penicillins or cephalosporins, which confirms the
      findings from prospective studies and suggests the use of routinely collected
      data as a valuable alternative to determine such differences in persistence of
      resistance.

PMID- 27865980
TI  - Aging of cerebral white matter.
AB  - White matter (WM) occupies a large volume of the human cerebrum and is mainly
      composed of myelinated axons and myelin-producing glial cells. The myelinated
      axons within WM are the structural foundation for efficient neurotransmission
      between cortical and subcortical areas. Similar to neuron-enriched gray matter
      areas, WM undergoes a series of changes during the process of aging. WM
      malfunction can induce serious neurobehavioral and cognitive impairments. Thus,
      age-related changes in WM may contribute to the functional decline observed in
      the elderly. In addition, aged WM becomes more susceptible to neurological
      disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration.
      In this review, we summarize the structural and functional alterations of WM in
      natural aging and speculate on the underlying mechanisms. We also discuss how age
      related WM changes influence the progression of various brain disorders,
      including ischemic and hemorrhagic stroke, TBI, Alzheimer's disease, and
      Parkinson's disease. Although the physiology of WM is still poorly understood
      relative to gray matter, WM is a rational therapeutic target for a number of
      neurological and psychiatric conditions.

PMID- 27865985
TI  - cfr-mediated linezolid-resistant clinical isolates of methicillin-resistant
      coagulase-negative staphylococci from China.
AB  - Three linezolid-resistant coagulase-negative staphylococci (LR-CoNS), including
      two Staphylococcus cohnii and one Staphylococcus capitis, were isolated from 1104
      clinical staphylococcal isolates across China in 2013-2014. Antibiotic
      susceptibilities of the bacteria were determined by the agar dilution method. PCR
      and DNA sequencing were performed to determine the potential molecular mechanism
      of linezolid resistance. The two linezolid-resistant S. cohnii isolates were
      subjected to pulsed-field gel electrophoresis (PFGE) to investigate their genetic
      relatedness. Primer walking, S1 nuclease PFGE and Southern blot hybridisation
      were conducted to ascertain the location and environment of the cfr gene. All
      three isolates were positive for the cfr gene. Amino acid mutations S158F and
      S158Y in the ribosomal protein L3 were identified in S. cohnii 13B289 and 13L105,
      respectively, both of which also had an additional substitution (D159Y) in L3.
      PFGE indicated that the two S. cohnii isolates belonged to diverse clonal
      strains. S1 nuclease PFGE and Southern blotting experiments indicated that the
      cfr gene of the three isolates resided on plasmids of similar size (ca. 35.4kb).
      The cfr-harbouring segments of S. capitis 13G350 and S. cohnii 13L105 were
      identical to plasmid pSS-01 reported previously. The cfr-carrying fragment of S.
      cohnii 13B289 was indistinguishable from the formerly described plasmid pSS-02.
      In conclusion, the presence of the cfr gene located on a plasmid was the main
      mechanism contributing to resistance to linezolid in the three staphylococcal
      isolates. Hence, timely detection and judicious use of antibiotics are essential
      to prevent further transmission of this resistance mechanism.

PMID- 27865984
TI  - Fabrication of liposomal doxorubicin exhibiting ultrasensitivity against
      phospholipase A2 for efficient pulmonary drug delivery to lung cancers.
AB  - Phospholipase A2 (PLA2) is expressed in inflammation-related tissue, including
      cancer tumors. We report that a hybrid liposome composed of phospholipid (DPPC)
      and PEGylated block-copolymer (Poloxamer 188) can rapidly release an encapsulated
      hydrophilic drug in the presence of PLA2. DPPC/P188 liposomes released
      approximately 80% of the encapsulated calcein (a fluorescence marker) within
      10min in the presence of 120 mU of PLA2 at 37 degrees C in vitro, whereas several
      other liposomal compositions used for inhalation therapy did not. DPPC/P188
      liposomes were stable in the absence of PLA2 at 37 degrees C after 60min
      incubation and drug release by PLA2 was dependent on the amount of P188
      incorporated into the DPPC liposomes. Drug release from doxorubicin (DOX,
      anticancer drug)-loaded DPPC/P188 liposomes was facilitated at higher PLA2
      concentrations and was dependent on the temperature and the presence of calcium
      ion, thus partially explaining PLA2-responsive drug release. DOX release from
      liposomes triggered by PLA2 exhibited the same cytotoxic effects on the A549 lung
      cancer cell line as did DOX in free solution. These findings suggest that
      DPPC/P188 liposomes are a promising drug carrier for delivering drug efficiently
      at PLA2-expressing sites such as inflammatory lung cancer.

PMID- 27865982
TI  - Hide and seek: How do DNA glycosylases locate oxidatively damaged DNA bases
      amidst a sea of undamaged bases?
AB  - The first step of the base excision repair (BER) pathway responsible for removing
      oxidative DNA damage utilizes DNA glycosylases to find and remove the damaged DNA
      base. How glycosylases find the damaged base amidst a sea of undamaged bases has
      long been a question in the BER field. Single molecule total internal reflection
      fluorescence microscopy (SM TIRFM) experiments have allowed for an exciting look
      into this search mechanism and have found that DNA glycosylases scan along the
      DNA backbone in a bidirectional and random fashion. By comparing the search
      behavior of bacterial glycosylases from different structural families and with
      varying substrate specificities, it was found that glycosylases search for damage
      by periodically inserting a wedge residue into the DNA stack as they redundantly
      search tracks of DNA that are 450-600bp in length. These studies open up a wealth
      of possibilities for further study in real time of the interactions of DNA
      glycosylases and other BER enzymes with various DNA substrates.

PMID- 27865987
TI  - Sexy online self-presentation on social network sites and the willingness to
      engage in sexting: A comparison of gender and age.
AB  - The present study investigated whether engaging in sexy self-presentations on
      social network sites (SNSs) or exposure to sexy self-presentations on SNSs
      predicts the willingness to engage in sexting. A second aim of the present study
      was to investigate whether adolescent girls demonstrate stronger relationships
      between (exposure to) sexy online self-presentations on SNSs and willingness to
      sext than adolescent boys and young adult men and women. A two-wave panel survey
      among 953 Dutch adolescents (13-17 years old, 50.7% male) and 899 Dutch young
      adults (18-25 years old, 43.9% male) showed that engaging in sexy self
      presentations on SNSs increased the willingness to engage in sexting, but only
      among adolescent girls. Exposure to sexy self-presentations of others did not
      predict the willingness to engage in sexting. The findings call for more research
      on the role of gender and age in the link between sexy self-presentation and
      sexting.

PMID- 27865988
TI  - Persistent and new-onset daytime sleepiness in pregnant women: A prospective
      observational cohort study.
AB  - BACKGROUND: Daytime sleepiness is a frequent complaint in women during pregnancy.
      It has also been linked to negative obstetric consequences. Although high
      prevalence of excessive daytime sleepiness throughout pregnancy is well
      documented, neither the causes of persistent daytime sleepiness nor new-onset
      daytime sleepiness during pregnancy have been investigated. Identifying
      predictive factors may play an important role in the management of daytime
      sleepiness in pregnant women and improve prenatal care and maternal-fetal
      outcomes. OBJECTIVES: To examine first-trimester maternal characteristics
      associated with the persistence and new-onset daytime sleepiness in pregnant
      women. DESIGN: A longitudinal, prospective cohort design. SETTING: One medical
      center in Taipei, Taiwan and participating women's homes. PARTICIPANTS: A total
      of 204 pregnant women. METHODS: First-trimester pregnant women recruited from an
      outpatient obstetric clinic at a medical center provided socio-demographic and
      health information, wore an actigraphy monitor for 7 days, and completed sleep,
      mood, and daytime sleepiness questionnaires. Data were collected again when the
      women were in the second and third trimester. RESULTS: Thirty-one (15.2%) women
      experienced excessive daytime sleepiness that persisted across all three
      trimesters. Nulliparous women and women who snored in the first trimester were
      2.28 and 2.10 times more at risk of being classified of persistent daytime
      sleepiness than multiparous women and women who did not snore in the first
      trimester, respectively. Thirty-one (15.2%) women developed new-onset daytime
      sleepiness with advancing gestation. Women were more likely to develop new-onset
      daytime sleepiness if they worked longer hours per week (OR=1.04, p<0.001), if
      they reported snoring (OR=6.75, p<0.001), and if they had elevated depressive
      symptoms in the first trimester of pregnancy (OR=1.09, p=0.01). CONCLUSIONS:
      Snoring in the first trimester is involved in both the persistence and new-onset
      of daytime sleepiness with elevated depressive symptoms related to new-onset
      daytime sleepiness in pregnant women. Findings suggest that intervention
      strategies for alleviating daytime sleepiness in pregnant women should focus on
      managing snoring and symptoms of depression in early trimesters with special
      attention to nulliparous and employed women.

PMID- 27865990
TI  - Exploring the link between gastric motility and intragastric drug distribution in
      man.
AB  - In drug development, the stomach is often considered to be a simple, one
      compartmental organ, a waiting room for transfer of an orally administered dosage
      form to the duodenum. However, factors such as gastric acidity and hydrodynamics
      in the gastric environment may influence drug disposition. Although a link
      between gastrointestinal drug behaviour and gastric motility has often been
      hypothesized, they have not been simultaneously investigated in humans yet. In
      this proof-of-concept study, the combination of a well-established intraluminal
      sampling technique with high-resolution manometric measurements in the
      gastrointestinal tract was evaluated. This new combination of in vivo techniques
      proved to be feasible from a practical point of view and yielded valuable
      additional information regarding intraluminal drug behaviour. As a first
      application, the link between fasted state gastric motility and (in)homogeneous
      distribution of an orally administered drug in the stomach was investigated in
      healthy subjects. To this end, drug concentrations were measured in different
      regions of the stomach after oral administration of a commercially available drug
      product (Gabbroral(r), 250mg paromomycin) during a specific period of gastric
      contractile activity. A clear trend towards better mixing of an orally
      administered drug with gastric contents was observed when dosed in the presence
      of gastric contractions, resulting in a more homogeneous distribution of the drug
      throughout the stomach compared to dosing in the absence of gastric contractions.

PMID- 27865989
TI  - Drug delivery across intact and disrupted skin barrier: Identification of cell
      populations interacting with penetrated thermoresponsive nanogels.
AB  - Nanoscaled soft particles, such as nanogels, can be designed to incorporate
      different types of compounds and release them in a controlled and triggered
      manner. Thermoresponsive nanogels (tNG), releasing their cargo above a defined
      temperature, are promising carrier systems for inflammatory skin diseases, where
      the temperature of diseased skin differs from that of healthy skin areas. In this
      study a polyglycerol-based tNG with diameter of 156nm was investigated for
      penetration and release properties upon topical application on ex vivo human skin
      with intact or disrupted barrier. Furthermore, temperature-triggered effects and
      the internalization of tNG by skin cells upon translocation to the viable skin
      layers were analyzed. The investigated tNG were tagged with indodicarbocyanine
      and loaded with fluorescein, so that fluorescent microscopy and flow cytometry
      could be used to evaluate simultaneously particle penetration and release of the
      fluorochrome. Topically applied tNG penetrated into the SC of both intact and
      disrupted skin explants. Only in barrier-disrupted skin significant amounts of
      released fluorochrome and tNG penetrated in the epidermis and dermis 2h after
      topical application. When a thermal trigger was applied by infrared radiation
      (30s, 3.9mJ/cm2), a significantly higher penetration of tNG in the SC and release
      of the dye in the epidermis were detected with respect to non-triggered samples.
      Penetrated tNG particles were internalized by skin cells in both epidermis and
      dermis. Only few CD1a-positive Langerhans cells associated with tNG were found in
      the epidermis. However, in the dermis a significant percentage of cells
      associated with tNG were identified to be antigen presenting cells, i.e. HLA
      DR+and CD206+cells. Thus, tNG represent promising carrier systems for the
      treatment of inflammatory skin diseases, not only because of their improved
      penetration and controlled release properties, but also because of their ability
      to effectively reach dermal dendritic cells in barrier-disrupted skin.

PMID- 27865991
TI  - Recent advances in multiaxial electrospinning for drug delivery.
AB  - Electrospun fibers have seen an insurgence in biomedical applications due to
      their unique characteristics. Coaxial and triaxial electrospinning techniques
      have added new impetus via fabrication of multilayered nano and micro-size
      fibers. These techniques offer the possibility of forming fibers with features
      such as blending, reinforced core, porous and hollow structure. The unique
      fabrication process can be used to tailor the mechanical properties, biological
      properties and release of various factors, which can potentially be useful in
      various controlled drug delivery applications. Harvesting these advantages,
      various polymers and their combinations have been explored in a number of drug
      delivery and tissue regeneration applications. New advances have shown the
      requirement of drug-polymer compatibility in addition to drug-solvent
      compatibility. We summarize recent findings using both hydrophilic and
      hydrophobic (or lipophilic) drugs in hydrophobic or hydrophilic polymers on
      release behavior. We also describe the fundamental forces involved during the
      electrospinning process providing insight to the factors to be considered to form
      fibers. Also, various modeling efforts on the drug release profiles are
      summarized. In addition new developments in the immune response to the
      electrospun fibers, and advances in scale-up issues needed for industrial size
      manufacturing.

PMID- 27865993
TI  - Fifteen-month-old infants' cortisol levels decrease after a 30-min-warm-up
      procedure.
AB  - Stress-induction procedures designed to increase cortisol levels in infants have
      been ineffective in many studies. One reason might be that infants did not have
      sufficient time to settle into the laboratory environment prior to the start of
      the stress induction, and thus already had high baseline levels of cortisol. In
      this study we investigate whether an extended warm-up period reduces infants'
      (N=22) cortisol levels. Fifteen-month-old infants' saliva cortisol was measured
      upon arrival at the laboratory. Then, they were allowed to play with their
      parent. After 30min, cortisol was measured again. There was a decrease in
      cortisol after 30min of free play. Our study suggests that infants' cortisol
      levels decrease when infants have the opportunity to acclimatize to the test
      environment. An extended warm-up phase prior to stress induction procedures might
      be necessary to reliably increase cortisol levels in infants.

PMID- 27865992
TI  - In 6- to 8-year-old children, hair cortisol is associated with body mass index
      and somatic complaints, but not with stress, health-related quality of life,
      blood pressure, retinal vessel diameters, and cardiorespiratory fitness.
AB  - OBJECTIVES: Hair cortisol measurement has become an increasingly accepted
      approach in endocrinology and biopsychology. However, while in adult research
      hair cortisol has been proposed as a relevant biomarker for chronic stress (and
      its adverse consequences), studies with children are scarce. Therefore, the goal
      of the present exploratory study was to examine the associations between hair
      cortisol concentrations (HCCs), stress, and a series of health-related outcomes
      in a sample of Swiss first grade schoolchildren. METHODS: The sample consisted of
      318 children (53% girls, Mage=7.26, SD=0.35). Hair strands were taken near the
      scalp from a posterior vertex position, and HCCs were tested for the first 3-cm
      hair segment. Parents provided information about their children's age, gender,
      parental education, children's stress (recent critical life events, daily
      hassles), health-related quality of life, and psychosomatic complaints. Body
      composition, blood pressure, retinal vessel diameters, and cardiorespiratory
      fitness were measured with established methods. RESULTS: In multiple regression
      analyses, higher HCCs were weakly associated with increased BMI in girls
      (beta=0.22, p<0.001), whereas higher HCCs were associated with increased somatic
      complaints in boys (beta=0.20, p<0.05). No significant relationships were found
      between HCCs and parental reports of stress, health-related quality of life,
      blood pressure, retinal vessel diameters, and cardiorespiratory fitness.
      CONCLUSIONS: Although small significant relationships were found between HCCs,
      BMI and somatic complaints, the findings of this exploratory study challenge the
      view that HCCs can be used as a reliable biomarker of recent critical life
      events, daily hassles, health-related quality of life, and cardiovascular health
      indicators in non-clinical young children.

PMID- 27865994
TI  - Phenanthroline-bis-oxazole ligands for binding and stabilization of G
      quadruplexes.
AB  - BACKGROUND: G-quadruplexes (G4) are found at important genome regions such as
      telomere ends and oncogene promoters. One prominent strategy to explore the
      therapeutic potential of G4 is stabilized it with specific ligands. METHODS: We
      report the synthesis of new phenanthroline, phenyl and quinoline acyclic
      bisoxazole compounds in order to explore and evaluate the targeting to c-myc and
      human telomeric repeat 22AG G4 using FRET-melting, CD-melting, NMR, fluorescence
      titrations and FID assays. RESULTS: The design strategy has led to potent
      compounds (Phen-1 and Phen-2) that discriminate different G4 structures (human
      telomeric sequences and c-myc promoter) and selectively stabilize G4 over duplex
      DNA. CD studies show that Phen-2 binds and induces antiparallel topologies in
      22AG quadruplex and also binds c-myc promotor, increasing their Tm in about 12
      degrees C and 30 degrees C respectively. In contrast, Phen-1 induces parallel
      topologies in 22AG and c-myc, with a moderate stabilization of 4 degrees C for
      both sequences. Consistent with a CD melting study, Phen-2 binds strongly (K=106
      to 107M-1) to c-myc and 22AG quadruplexes. CONCLUSIONS: Phen-1 and Phen-2
      discriminated among various quadruplex topologies and exhibited high selectivity
      for quadruplexes over duplexes. Phen-2 retains antiparallel topologies for
      quadruplex 22AG and does not induce conformational changes on the parallel c-myc
      quadruplex although Phen-1 favors the parallel topology. NMR studies also showed
      that the Phen-2 binds to the c-myc quadruplex via end stacking. GENERAL
      SIGNIFICANCE: Overall, the results suggest the importance of Phen-2 as a scaffold
      for the fine-tuning with substituents in order to enhance binding and
      stabilization to G4 structures. This article is part of a Special Issue entitled
      "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

PMID- 27865995
TI  - G-quadruplex-based aptamers against protein targets in therapy and diagnostics.
AB  - Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to
      recognize with high affinity specific targets including proteins, small
      molecules, ions, whole cells and even entire organisms, such as viruses or
      bacteria. They can be identified from combinatorial libraries of DNA or RNA
      oligonucleotides by SELEX technology, an in vitro iterative selection procedure
      consisting of binding (capture), partitioning and amplification steps.
      Remarkably, many of the aptamers selected against biologically relevant protein
      targets are G-rich sequences that can fold into stable G-quadruplex (G4)
      structures. Aiming at disseminating novel inspiring ideas within the scientific
      community in the field of G4-structures, the emphasis of this review is placed
      on: 1) recent advancements in SELEX technology for the efficient and rapid
      identification of new candidate aptamers (introduction of microfluidic systems
      and next generation sequencing); 2) recurrence of G4 structures in aptamers
      selected by SELEX against biologically relevant protein targets; 3) discovery of
      several G4-forming motifs in important regulatory regions of the human or viral
      genome bound by endogenous proteins, which per se can result into potential
      aptamers; 4) an updated overview of G4-based aptamers with therapeutic potential
      and 5) a discussion on the most attractive G4-based aptamers for diagnostic
      applications. This article is part of a Special Issue entitled "G-quadruplex"
      Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.

PMID- 27865996
TI  - In vivo effects of metal ions on conformation and mechanical performance of
      silkworm silks.
AB  - BACKGROUND: The mechanism of silk fiber formation is of particular interest.
      Although in vitro evidence has shown that metal ions affect conformational
      transitions of silks, the in vivo effects of metal ions on silk conformations and
      mechanical performance are still unclear. METHODS: This study explored the
      effects of metal ions on silk conformations and mechanical properties of silk
      fibers by adding K+ and Cu2+ into the silk fibroin solutions or injecting them
      into the silkworms. Aimed by CD analysis, FTIR analysis, and mechanical testing,
      the conformational and mechanical changes of the silks were estimated. By using
      BION Web Server, the interactions of K+ and N-terminal of silk fibroin were also
      simulated. RESULTS: We presented that K+ and Cu2+ induced the conformational
      transitions of silk fibroin by forming beta-sheet structures. Moreover, the
      mechanical parameters of silk fibers, such as strength, toughness and Young's
      modulus, were also improved after K+ or Cu2+ injection. Using BION Web Server, we
      found that potassium ions may have strong electrostatic interactions with the
      negatively charged residues. CONCLUSION: We suggest that K+ and Cu2+ play crucial
      roles in the conformation and mechanical performances of silks and they are
      involved in the silk fiber formation in vivo. GENERAL SIGNIFICANCE: Our results
      are helpful for clarifying the mechanism of silk fiber formation, and provide
      insights for modifying the mechanical properties of silk fibers.

PMID- 27865998
TI  - Intensive LDL-cholesterol lowering therapy and neurocognitive function.
AB  - The key lipid-lowering target is to achieve guideline-recommended low-density
      lipoprotein cholesterol (LDL-C) levels, usually by using statins. The new
      treatment strategies for lipid-lowering therapy include using proprotein
      convertase subtilisin/kexin type 9 (PCSK9) inhibitors as an exciting approach to
      reduce residual risk of cardiovascular diseases (CVD). However, concerns about
      possible adverse effects, including neurocognitive disorders, were issued by the
      Food and Drug Administration (FDA). The current disputable evidence does not
      allow definite conclusions as to whether statins contribute to, or cause,
      clinically meaningful cognitive impairment. Some evidence indicates a high rate
      of memory loss, while other evidence suggests a benefit in dementia prevention.
      This debate should not discourage appropriate statin and other lipid-lowering
      drug administration. However, prescribers should be aware of such potential drug
      related side effects. Prospective controlled studies comparing the short- and
      long-term effects of different statins on cognitive function are warranted. The
      effects of intensive LDL-C lowering on neurocognition might be attributed to an
      off-target effect. It is also possible that pre-existing pathology and vascular
      risk may already be present outweighing any effect related to lipids. Gender,
      genetic, LDL-C-related genotypes and aging-related changes should also be
      considered. Some data indicate that carriers of apolipoprotein E (apoE) epsilon-4
      allele, with low levels of apoA1 and high-density lipoprotein cholesterol have a
      distinct plasma lipid profile and may be more susceptible to neurocognitive
      dysfunction. Future research on lipid-lowering drugs and cognition is needed;
      careful study design and analysis will be critical.

PMID- 27865999
TI  - Approaches to improve metabolic stability of a statine-based GRP receptor
      antagonist.
AB  - : The bombesin receptor family, in particular the gastrin-releasing peptide
      receptor (GRPr), is an attractive target in the field of nuclear oncology due to
      the high density of these receptors on the cell surface of several human tumors.
      The successful clinical implementation of 64Cu-CB-TE2A-AR06, 68Ga-RM2 and 68Ga
      NODAGA-MJ9, prompted us to continue the development of GRPr-antagonists. The aim
      of the present study was to assess if N-terminal modulations of the statine-based
      GRPr-antagonist influence the binding affinity, the pharmacokinetic performance
      and the in vivo metabolic stability. METHODS: The GRPr-antagonist (D-Phe-Gln-Trp
      Ala-Val-Gly-His-Sta-Leu-NH2) was functionalized with the chelator 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) via the spacer 4-amino-1
      carboxymethyl-piperidine (Pip) and the amino acid N-Methyl-beta-Ala, to obtain
      NMe-RM2 and labeled with 68Ga and 177Lu. The GRPr affinity of the corresponding
      metalloconjugates determined using [125I-Tyr4]-BN as radioligand. In vitro
      evaluation included internalization studies using PC3 cells. The 68Ga-conjugate
      was evaluated in PC3 xenografts by biodistribution and PET studies, while
      investigations on the metabolic stability and plasma protein binding were
      performed. RESULTS: The half maximum inhibitory concentrations (IC50) of the
      metalloconjugates, using [125I-Tyr4]-BN, are in the low nanomolar range. PC3-cell
      culture binding studies of both metallated NMe-RM2 and RM2 show high GRPr-bound
      activity and low internalization. Metabolic studies showed that 68Ga-NMe-RM2 and
      68Ga-RM2 are being cleaved in a similar fashion into three metabolites, with a
      good proportion of about 50% of the remaining blood activity at 15min post
      injection (p.i.) being represented by the intact radiotracer. 68Ga-NMe-RM2 was
      shown to target specifically PC3 xenografts, with high and sustained tumor uptake
      of about 13% IA/g within a time frame of 3h. The PET images clearly visualized
      the tumor. CONCLUSIONS: The relatively high percentage of the remaining intact
      radiotracer in blood 15min post injection sufficiently enables in vivo targeting
      of GRPr positive tumors, finding which has been also shown in clinical trials.

PMID- 27865997
TI  - Homogentisic acid induces aggregation and fibrillation of amyloidogenic proteins.
AB  - BACKGROUND: Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism
      characterized by homogentisic acid (HGA) accumulation due to a deficient activity
      of the homogentisate 1.2-dioxygenase (HGD) enzyme. This leads to the production
      of dark pigments that are deposited onto connective tissues, a condition named
      'ochronosis' and whose mechanisms are not completely clear. Recently, the
      potential role of hitherto unidentified proteins in the ochronotic process was
      hypothesized, and the presence of Serum Amyloid A (SAA) in alkaptonuric tissues
      was reported, allowing the classification of AKU as a novel secondary
      amyloidosis. METHODS: Gel electrophoresis, Western Blot, Congo Red-based assays
      and electron microscopy were used to investigate the effects of HGA on the
      aggregation and fibrillation propensity of amyloidogenic proteins and peptides
      [Abeta(1-42), transthyretin, atrial natriuretic peptide, alpha-synuclein and
      SAA]. LC/MS and in silico analyses were undertaken to identify possible binding
      sites for HGA (or its oxidative metabolite, a benzoquinone acetate or BQA) in
      SAA. RESULTS: We found that HGA might act as an amyloid aggregation enhancer in
      vitro for all the tested proteins and peptides in a time- and dose- dependent
      fashion, and identified a small crevice at the interface between two HGD subunits
      as a candidate binding site for HGA/BQA. CONCLUSIONS: HGA might be an important
      amyloid co- component playing significant roles in AKU amyloidosis. GENERAL
      SIGNIFICANCE: Our results provide a possible explanation for the clinically
      verified onset of amyloidotic processes in AKU and might lay the basis to setup
      proper pharmacological approaches to alkaptonuric ochronosis, which are still
      lacking.

PMID- 27866000
TI  - Effectiveness of final decontamination protocols against Enterococcus faecalis
      and its influence on bond strength of filling material to root canal dentin.
AB  - AIM: The aim of this study was to evaluate the effectiveness of final
      decontamination protocols against Enterococcus faecalis and their influence on
      bond strength of filling material to root canal dentin. MATERIAL AND METHODS:
      Ninety root canals were enlarged with ProTaper system and inoculated with E.
      faecalis for 15days. Sixty samples were randomly divided into six groups (n=10)
      and subjected to following protocols: G1-distilled water(control), G2-2%
      chlorhexidine, G3-QMix, G4-6.5% grape seed extract, G5-photodynamic therapy with
      optical fiber and G6-photodynamic therapy without optical fiber. The percentage
      of bacterial reduction was checked by counting of CFUs. The remaining 30 samples
      were subjected to the same decontamination protocols (n=5) and filled with gutta
      percha and AH Plus sealer in order to perform the push-out test. Data from both
      tests were subjected to one-way ANOVA followed by Tukey's post hoc procedure
      (alpha=0.05). RESULTS: The greatest bacterial reduction was observed for 2%
      chlorhexidine, QMix and 6.5% grape seed extract, with no statistically
      significant difference between them. Photodynamic therapy, with and without
      optical fiber, demonstrated a significantly higher reduction than distilled
      water, with no statistically significant difference between them (p<0.05). For
      the push-out test, final decontamination protocols showed similar bond strength
      values (p<0.05), with the highest incidence of cohesive failure in all groups.
      CONCLUSIONS: The tested final decontamination protocols showed effectiveness
      against E. faecalis and did not interfere with the bond strength of filling
      material to root canal dentin.

PMID- 27866003
TI  - News from the plant world: Listening to transcription.

PMID- 27866002
TI  - Live bio-imaging with fully bio-compatible organic fluorophores.
AB  - We synthesized a new organic fluorescent dye named resveratrone glucoside from
      the photoreaction of naturally-occurring phytoalexin compound resveratrol
      glucoside (resveratrol-3-beta-mono-d-glucoside), which is abundant in various
      plants such as berries, herbs, nuts and grapes. Just like its predecessor
      molecule resveratrone that was previously discovered by our group, resveratrone
      glucoside possesses excellent optical properties including a high fluorescence
      quantum yield, a large Stokes' shift, and a large two-photon absorption cross
      section. In addition to these highly desirable properties, both fluorescent
      molecules can also be used as ideal bio-compatible organic fluorophores since
      they have remarkably low cytotoxicity, which we verified through our cell
      morphological study, trypan blue exclusion assay, Western blot analysis and
      fluorescence imaging of various live biological specimens. In particular, we note
      that resveratrone glucoside is much more soluble in aqueous solution because of
      its glycosidic side chain and therefore highly suitable for in vivo imaging. We
      demonstrated that resveratrone and resveratrone glucoside can be used in one- and
      two-photon fluorescence microscopic imaging of E. coli, yeast (S. cerevisiae),
      and mammalian cell lines including HeLa and MCF10A cells as well as to the live
      imaging and real-time tracking of the zebrafish embryo development. Both organic
      fluorophores can be readily obtained from a simple photoreaction of commercially
      available, inexpensive samples.

PMID- 27866001
TI  - Generating disease-pertinent treatment vocabularies from MEDLINE citations.
AB  - OBJECTIVE: Healthcare communities have identified a significant need for disease
      specific information. Disease-specific ontologies are useful in assisting the
      retrieval of disease-relevant information from various sources. However, building
      these ontologies is labor intensive. Our goal is to develop a system for an
      automated generation of disease-pertinent concepts from a popular knowledge
      resource for the building of disease-specific ontologies. METHODS: A pipeline
      system was developed with an initial focus of generating disease-specific
      treatment vocabularies. It was comprised of the components of disease-specific
      citation retrieval, predication extraction, treatment predication extraction,
      treatment concept extraction, and relevance ranking. A semantic schema was
      developed to support the extraction of treatment predications and concepts. Four
      ranking approaches (i.e., occurrence, interest, degree centrality, and weighted
      degree centrality) were proposed to measure the relevance of treatment concepts
      to the disease of interest. We measured the performance of four ranks in terms of
      the mean precision at the top 100 concepts with five diseases, as well as the
      precision-recall curves against two reference vocabularies. The performance of
      the system was also compared to two baseline approaches. RESULTS: The pipeline
      system achieved a mean precision of 0.80 for the top 100 concepts with the
      ranking by interest. There were no significant different among the four ranks
      (p=0.53). However, the pipeline-based system had significantly better performance
      than the two baselines. CONCLUSIONS: The pipeline system can be useful for an
      automated generation of disease-relevant treatment concepts from the biomedical
      literature.

PMID- 27866004
TI  - Attention capture without awareness in a non-spatial selection task.
AB  - Distractors presented prior to a critical target in a rapid sequence of visually
      presented items induce a lag-dependent deficit in target identification,
      particularly when the distractor shares a task-relevant feature of the target.
      Presumably, such capture of central attention is important for bringing a target
      into awareness. The results of the present investigation suggest that greater
      capture of attention by a distractor is not accompanied by greater awareness of
      it. Moreover, awareness tends to be limited to superficial characteristics of the
      target such as colour. The findings are interpreted within the context of a model
      that assumes sudden increases in arousal trigger selection of information for
      consolidation in working memory. In this conceptualization, prolonged analysis of
      distractor items sharing task-relevant features leads to larger target
      identification deficits (i.e., greater capture) but no increase in awareness.

PMID- 27866005
TI  - Interoception and gender: What aspects should we pay attention to?
AB  - Interoception is involved in both somatic and mental disorders with different
      prevalence between genders; however, gender differences are often neglected. To
      examine the potential gender differences in interoceptive awareness, we recruited
      376 healthy subjects (51% males, aged 17-30years), to fill in the
      Multidimensional Assessment of Interoceptive Awareness (MAIA). Of that sample, in
      a subgroup of 40 subjects (50% males), interoceptive accuracy was assessed by
      heartbeat counting task (HCT). The results on interroceptive awareness suggest
      that females tendto notice bodily sensations more often, better understand
      relations between bodily sensations and emotional states, worry or experience
      more emotional distress with sensations of pain or discomfort and see body as
      less safe. The results of interoceptive accuracy further suggest that females are
      less efficient in consciously detecting heartbeats. Therefore, gender should be
      considered when interoceptive evaluation is performed in disorders associated to
      bodily sensations and to the emotional/mood states.

PMID- 27866007
TI  - Continuous manufacturing via hot-melt extrusion and scale up: regulatory matters.
AB  - Currently, because globalization, the pharmaceutical industry is facing enormous
      challenges to comply with regulatory matters. Reduced patent life and overall
      decreased profitability of newly discovered drugs are also forcing the
      pharmaceutical industry to shorten the drug development time with maximum
      throughput. Therefore, continuous manufacturing (CM) processes via hot melt
      extrusion (HME) can be a promising alternative for achieving these goals. HME
      offers solvent-free green technology with a process that is easy to scale up.
      Moreover, CM provides better product quality assurance compared with batch
      processes, with fewer labor costs and shorter time to development. In this
      review, we primarily focus on various aspects of CM and the emerging application
      of HME to bridge the current manufacturing gap in pharmaceutical sphere.

PMID- 27866006
TI  - The Cardiovascular Safety of Dutasteride.
AB  - PURPOSE: Randomized controlled trials suggest an increased risk of heart failure
      with dutasteride, which inhibits both the type 1 and type 2 isoforms of 5alpha
      reductase. In contrast, no such association has been suggested for finasteride,
      which selectively inhibits the type 2 isoform. We investigated the risk of
      cardiovascular events among patients receiving dutasteride relative to
      finasteride. MATERIALS AND METHODS: We performed a population based cohort study
      of Ontario men 66 years old or older who commenced treatment with dutasteride or
      finasteride between October 1, 2005 and March 31, 2015. For each individual
      treated with dutasteride, we identified 1 treated with finasteride, matching on a
      propensity score and calendar quarter of treatment initiation to account for
      temporal changes in prescribing. The primary outcome was hospitalization for
      heart failure. Secondary analyses were done to examine acute myocardial
      infarction and stroke. Cox proportional hazards regression was used to adjust for
      differences between groups. RESULTS: We studied 36,311 men who commenced
      dutasteride and 36,311 treated with finasteride. In the primary analysis, we
      found no difference in the risk of heart failure among patients receiving
      dutasteride relative to those receiving finasteride (adjusted HR 0.98, 95% CI
      0.88-1.08). Similarly, we found no difference in the risk of acute myocardial
      infarction (HR 0.94, 95% CI 0.82-1.08) or stroke (HR 1.03, 95% CI 0.88-1.20).
      CONCLUSIONS: In this population based cohort study of more than 72,000 older men,
      dutasteride was not associated with an increased risk of cardiovascular events
      relative to finasteride.

PMID- 27866008
TI  - Organs-on-chips: research and commercial perspectives.
AB  - Traditional preclinical drug testing methods utilize animal models to predict
      pharmacology and toxicology profiles. However, the data obtained from such
      methods cannot be directly extrapolated to humans and often do not provide a safe
      starting dose for first-in-human studies. To overcome these limitations,
      researchers have developed organs-on-chips - microfluidic devices that can mimic
      the cellular architecture and physiology more accurately than conventional
      methods. Because accurate organ-level interactions can be achieved with these
      devices, they have the potential to provide a realistic determination of a drug's
      pharmacokinetics, pharmacodynamics and toxicity profile. In this review, we
      describe the evolution of the technology and provide an overview of its current
      applications. We also discuss the current industry and government initiatives in
      promoting further research on organs-on-chips for potential use during drug
      development.

PMID- 27866009
TI  - Commercialisation of CAR T-cell therapies: business model spectrum.

PMID- 27866010
TI  - The botanical explorer's legacy: a promising bioprospecting tool.
AB  - Records about the traditional uses of medicinal plants can be considered useful
      in bioprospecting (i.e., the search for new active agents or lead structures in
      nature). Several sources like Egyptian papyri, early modern herbals and
      pharmacopoeias have been studied in this respect. It is proposed to use
      recordings of botanically interested explorers of the 19th and early 20th
      centuries as well. Some of them give detailed information about traditionally
      used medicinal plants and analysis shows that a considerable number of these have
      never been scientifically investigated. Existing studies, however, are confirming
      the traditional uses described to a great extent. Thus, the explorer's writings
      should not be neglected while looking for starting points for plant screening;
      success seems more likely than with screening at random.

PMID- 27866011
TI  - Protected Mealtimes in hospitals and nutritional intake: Systematic review and
      meta-analyses.
AB  - OBJECTIVES: Protected Mealtimes is an intervention developed to address the
      problem of malnutrition, particularly in the hospital setting. The intervention
      aims to provide interruption-free time to eat during a hospital admission, thus
      supporting increased nutritional intake. This review aimed to determine the
      impact of Protected Mealtimes on the nutritional intake of hospitalised patients.
      DESIGN: The review was registered with the PROSPERO International Prospective
      Register of Systematic Reviews (CRD42015023423) and followed the PRISMA
      guidelines. Meta-analyses were conducted of energy and protein intake. DATA
      SOURCES: Seven databases were searched to identify relevant publications: Ovid
      MEDLINE, Embase, CINAHL Plus, PsycInfo, Scopus, Cochrane Library (including NHS
      economic evaluations), and NICE clinical guidelines. A supplementary internet
      search of Google and Google Scholar was undertaken. The search terms protect* AND
      (mealtime* OR "meal time*") were used for all searches. REVIEW METHODS: Eligible
      studies were original research where Protected Mealtimes was implemented in
      hospitals and nutritional intake measured. Studies were selected for inclusion
      following a systematic process of identification, screening and eligibility
      assessment. Two authors completed the screening and eligibility assessment, and
      quality assessment of included studies. The Quality Criteria Checklist for
      Primary Research was used to evaluate the quality of each study, whilst the
      overall body of evidence was assessed using the GRADE approach. One author
      extracted data and ran the meta-analyses, these were verified by a second author.
      RESULTS: Database and hand searching yielded 150 papers for consideration; the
      final review library was seven studies where nutritional intake of patients had
      been evaluated before and after the introduction of Protected Mealtimes. No
      clinical trials of the intervention were identified. The meta-analyses of energy
      and protein intake in four observational studies found no effect in favour of
      Protected Mealtimes implementation. The GRADE of evidence was rated as very low.
      CONCLUSIONS: Given the small number of observational studies and the quality of
      evidence on the effect of the intervention on nutritional intake, we conclude
      that there is insufficient evidence for widespread implementation of Protected
      Mealtimes in hospitals. More research including clinical trials, with subgroup
      reporting of patients' nutritional status and estimated energy requirements are
      needed to further understand the merits of this complex healthcare intervention.

PMID- 27866013
TI  - A whole genome gene content phylogenetic analysis of anopheline mosquitoes.
AB  - Construction of stringent gene content matrices was accomplished for 21
      Anopheline mosquito species and strains and four outgroups species. The presence
      absence matrix using e-75 as a cutoff in single linkage clustering had over
      17,000 ortholog groups. We used the gene content matrix to generate a
      phylogenetic hypothesis that is in general agreement with gene sequence based
      phylogenies. In addition to establishing a congruent gene content phylogeny we
      examined the consistency of three methods for analyzing presence absence data -
      unweighted parsimony, dollo parsimonly and maximum likelihood using a BINGAMMA
      model. An examination of the chromosomal location of the gains and losses in the
      presence absence matrix revealed a low frequency of gains and losses at
      centromeres and tips of chromosomes.

PMID- 27866012
TI  - Differential activation of the frontal pole to high vs low calorie foods: The
      neural basis of food preference in Anorexia Nervosa?
AB  - Neuroimaging studies in anorexia nervosa (AN) suggest that altered food reward
      processing may result from dysfunction in both limbic reward and cortical control
      centers of the brain. This fMRI study aimed to index the neural correlates of
      food reward in a subsample of individuals with restrictive AN: twelve currently
      ill, fourteen recovered individuals and sixteen healthy controls. Participants
      were shown pictures of high and low-calorie foods and asked to evaluate how much
      they wanted to eat each one following a four hour fast. Whole-brain task
      activated analysis was followed by psychophysiological interaction analysis (PPI)
      of the amygdala and caudate. In the AN group, we observed a differential pattern
      of activation in the lateral frontal pole: increasing following presentation of
      high-calorie stimuli and decreasing in during presentation of low-calorie food
      pictures, the opposite of which was seen in the healthy control (HC) group. In
      addition, decreased activation to food pictures was observed in somatosensory
      regions in the AN group. PPI analyses suggested hypo-connectivity in reward
      pathways, and between the caudate and both somatosensory and visual processing
      regions in the AN group. No significant between-group differences were observed
      between the recovered group and the currently ill and healthy controls in the PPI
      analysis. Taken together, these findings further our understanding of the neural
      processes which may underpin the avoidance of high-calorie foods in those with AN
      and might exacerbate the development of compulsive weight-loss behavior, despite
      emaciation.

PMID- 27866014
TI  - 3D Multi-segment foot kinematics in children: A developmental study in typically
      developing boys.
AB  - BACKGROUND: The relationship between age and 3D rotations objectivized with
      multisegment foot models has not been quantified until now. The purpose of this
      study was therefore to investigate the relationship between age and multi-segment
      foot kinematics in a cross-sectional database. METHODS: Barefoot multi-segment
      foot kinematics of thirty two typically developing boys, aged 6-20 years, were
      captured with the Rizzoli Multi-segment Foot Model. One-dimensional statistical
      parametric mapping linear regression was used to examine the relationship between
      age and 3D inter-segment rotations of the dominant leg during the full gait
      cycle. RESULTS: Age was significantly correlated with sagittal plane kinematics
      of the midfoot and the calcaneus-metatarsus inter-segment angle (p<0.0125). Age
      was also correlated with the transverse plane kinematics of the calcaneus
      metatarsus angle (p<0.0001). CONCLUSION: Gait labs should consider age related
      differences and variability if optimal decision making is pursued. It remains
      unclear if this is of interest for all foot models, however, the current study
      highlights that this is of particular relevance for foot models which incorporate
      a separate midfoot segment.

PMID- 27866015
TI  - Diversity selection, screening and quantitative structure-activity relationships
      of osmolyte-like additive effects on the thermal stability of a monoclonal
      antibody.
AB  - Solvents used for therapeutic proteins in downstream processing and in
      formulations often contain stabilizing additives that inhibit denaturation and
      aggregation. Such additives are mostly selected based on their positive effect on
      thermal stability of the protein, and are often derived from naturally occuring
      osmolytes. To better understand the structural basis underlying the effect of
      additives, we selected a diverse library of compounds comprising 79 compounds of
      the polyol, amino acid and methylamine chemical classes and determined the effect
      of each compound on thermal stability of a monoclonal antibody as a function of
      compound concentration. Thermal stabilization of the antibody was influenced by
      solution pH. Quantitative structure-activity relationships (QSAR) were derived by
      partial least squares regression for individual compound classes and globally.
      The global model suggests that ligands with a phenyl ring will decrease the Tm,
      while highly soluble, polar compounds with at least two hydrogen bond donors will
      increase the Tm. This approach may be beneficial for further studies on the
      influence of other solution conditions like ionic strength and buffer species on
      additive-mediated protein stabilization.

PMID- 27866016
TI  - Successful co-encapsulation of benzoyl peroxide and chloramphenicol in liposomes
      by a novel manufacturing method - dual asymmetric centrifugation.
AB  - Encapsulation of more than one active pharmaceutical ingredient into nanocarriers
      such as liposomes is an attractive approach to achieve a synergic drug effect and
      less complicated dosing schedules in multi-drug treatment regimes. Liposomal drug
      delivery in acne treatment may improve drug efficiency by targeted delivery to
      pilosebaceous units, reduce adverse effects and improve patient compliance. We
      therefore aimed to co-encapsulate benzoyl peroxide (BPO) and chloramphenicol
      (CAM) into liposomes using the novel liposome processing method - dual asymmetric
      centrifugation (DAC). Liposomes were formed from soybean lecithin, propylene
      glycol and distilled water (2:1:2w/v/v ratio), forming a viscous liposome
      dispersion. Liposomes containing both drugs (BPO-CAM-Lip), single drug (BPO-Lip
      and CAM-Lip), and empty liposomes were prepared. Drug entrapment of BPO and CAM
      was determined by a newly developed HPLC method for simultaneous detection and
      quantification of both drugs. Encapsulation of around 50% for BPO and 60% for CAM
      respectively was obtained in both single-drug encapsulated formulations (BPO-Lip
      and CAM-Lip) and co-encapsulated formulations (BPO-CAM-Lip). Liposome sizes were
      comparable for all liposome formulations, ranging from 130 to 150nm mean
      diameter, with a polydispersity index <0.2 for all formulations. CAM exhibited a
      sustained release from all liposomal formulations, whereas BPO appeared retained
      within the liposomes. BPO retention could be attributed to its poor solubility.
      However, HaCaT cell toxicity was found dependent on BPO released from the
      liposomes. In the higher concentration range (4%v/v), liposomal formulations were
      less cytotoxic than the corresponding drug solutions used as reference. We have
      demonstrated that DAC is a fast, easy, suitable method for encapsulation of more
      than one drug within the same liposomes.

PMID- 27866018
TI  - Intravenous beta-blockers in ST-segment elevation myocardial infarction: A
      systematic review and meta-analysis.
AB  - BACKGROUND/OBJECTIVES: The role of intravenous (IV) beta-blockers in conjunction
      with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial
      infarction (STEMI) remains unclear. We therefore conducted a meta-analysis to
      assess their role in the acute phase of STEMI. METHODS: We systematically
      searched the Cochrane Libraries, Medline, and EMBASE for RCTs comparing IV beta
      blockers with inactive controls in STEMI patients undergoing PCI. The primary
      outcome was left ventricular ejection fraction (LVEF). Pooling was performed
      using DerSimonian and Laird random-effects models. RESULTS: Four RCTs (n=1149)
      were included in our meta-analysis. All RCTs only enrolled patients with
      confirmed STEMI with symptoms lasting <6 or <12hours, and presenting in Killip
      Class 1 or 2. Mean age ranged across trials from 58.5-62.5years. Most patients
      were male (range: 74.8%-86.3%). Data suggest that IV beta-blockers may improve
      LVEF at 0-2weeks (weighted mean difference [WMD]: 1.9%; 95% confidence interval
      [CI]: -0.7%, 4.5%) and 4-6weeks (WMD: 1.4%; 95% CI: -3.1%, 5.9%) post-infarct,
      reaching statistical significance at 24weeks (WMD: 2.6%; 95% CI: 0.6%, 4.6%).
      Rates of ventricular arrhythmia (risk ratio [RR]: 0.65; 95% CI: 0.33, 1.29), any
      arrhythmia (RR: 0.67; 95% CI: 0.36, 1.27), and cardiogenic shock (RR: 0.77; 95%
      CI: 0.31, 1.95) during index hospitalization were numerically lower with IV beta
      blockers, but 95% CIs were wide. CONCLUSIONS: In STEMI patients presenting in
      Killip Class 1 or 2, IV beta-blockers in conjunction with PCI are associated with
      improved LVEF at 24weeks relative to PCI alone.

PMID- 27866019
TI  - Dysregulated fatty acid metabolism in coronary ectasia: An extended lipidomic
      analysis.
AB  - BACKGROUND: Coronary artery ectasia (CAE) is not an uncommon clinical condition,
      which could be associated with adverse outcome. The exact pathophysiology of the
      disease is poorly understood and is commonly interpreted as a variant of
      atherosclerosis. In this study, we sought to undertake lipidomic profiling of a
      group of CAE patients in an attempt to achieve better understanding of its
      disturbed metabolism. METHODS: Untargeted lipid profiling and complementary
      modelling strategies were employed to compare serum samples from 16 patients with
      CAE (mean age 63.5+/-10.1years, 6 female) and 26 controls with normal smooth
      coronary arteries (mean age 59.2+/-6.6years and 7 female). Sample preparation, LC
      MS analysis and metabolite identification were performed at the Swedish
      Metabolomics Centre, Umea, Sweden. RESULTS: Phosphatidylcholine levels were
      significantly distorted in the CAE patients (p=0.001-0.04). Specifically, 16
      carbon fatty acyl chain phosphatidylcholines (PC) were detected in lower levels.
      Similarly, 11 meioties of Sphyngomyelin (SM) species were detected at lower
      concentrations (p=0.000001-0.01) in the same group. However, only three
      metabolites were significantly higher in the pure CAE subgroup (6 patients) when
      compared with the 10 mixed CAE patients (two meioties of SM species and one of
      PC). Atherosclerosis risk factors were not different between groups. CONCLUSION:
      This is the first lipid profiling study reported in coronary artery ectasia.
      While the lower concentration and dysregulation of sphyngomyelin suggests an
      evidence for premature apoptosis, that of phosphatidylcholines suggests perturbed
      fatty acid elongation/desaturation, thus may be indicative of non-atherogenic
      process in CAE.

PMID- 27866017
TI  - Safety of optical coherence tomography in pediatric heart transplant patients.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is a crucial problem after heart
      transplantation, in adults as well as in children. CAV is the main risk factor
      for a reduced long-term graft survival. The early diagnosis and treatment of CAV
      is essential for a successful long-term preservation of the donor heart. However,
      asymptomatic progression of CAV and concentric hyperplasia of the coronary
      arteries may complicate the early diagnosis by conventional measures.
      Intravascular imaging, such as intravascular ultrasound and optical coherence
      tomography (OCT), enables the diagnosis of early stage CAV. To date, there is
      little known about OCT in children. We present our single center experience with
      OCT after pediatric heart transplantation. METHODS: Retrospective analysis of OCT
      (n=50) after pediatric heart transplantation between June 2013 and March 2016 and
      comparison between angiographic appearance and OCT. RESULTS: 37 patients
      underwent optical coherence tomography, nine patients were examined twice and two
      patients tree times. The youngest patient at time of examination was 4years with
      a weight of 15kg (mean 50.86kg, range 15 to 88kg). There were no complications,
      especially no bleeding, no arrhythmias or myocardial ischemic events. Early CAV
      (Stanford I or II) was detected by OCT in 26 cases. Only in four of these cases,
      also the coronary angiography showed mild changes. CONCLUSION: OCT is a safe
      intravascular imaging method that can also be used in children after pediatric
      heart transplantation up to a minimum weight of 15kg without an increasing risk
      of a catheterization procedure.

PMID- 27866020
TI  - Clinical manifestation and surgical treatment analysis of five cases with
      biatrial myxoma.
AB  - BACKGROUND: Cardiac myxomas (CMs) are a major primary heart tumor which often
      causes unexpected symptoms or sudden death. Among CMs, biatrial myxomas are even
      rare. This study was designed to investigate the clinical characteristics and
      surgical treatment of 5 cases with biatrial myxoma, to summarize the treatment
      experience and the effect of short-to-mid-term prognosis. METHODS: Five patients
      with biatrial myxoma were included in this study. The patients' relative
      literature, chest X-ray, body-surface electrocardiogram, and ultrasonic
      cardiogram (UCG) were used to investigate the clinical characteristics. The
      experience of surgical treatment and perioperative treatment were analyzed.
      RESULTS: Among the 5 cases, patients had presented discomfort of precordial area
      and cardiac insufficiency symptoms such as dyspnea and chest discomfort. There
      were characteristic changes on echocardiography (ECG). All patients accepted
      resection of both tumor and its basement tissue. Their symptoms were all improved
      after surgery, no deaths occurred. CONCLUSION: In conjunction with clinical
      features, diagnostic clue and echocardiography, the detectable rate of biatrial
      myxoma could be significantly improved. Early diagnosis showed good effect on
      prognosis.

PMID- 27866021
TI  - Early pulmonary arterial hypertension immediately after closure of a ventricular
      or complete atrioventricular septal defect beyond 6months of age.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is virtually absent after
      closure of ventricular septal defect (VSD) in the first six months of life.
      However the prevalence of PAH in patients, who underwent VSD closure later, is
      not clear. The aim of this study was to analyse the prevalence of PAH after a
      successful VSD closure after the age of 6months and whether there are risk
      factors for developing PAH. METHODS: Echocardiographic and right heart catheter
      data of patients with VSD or complete atrioventricular septal defect, who
      underwent VSD closure after the age of 6months in our institution between 01/2005
      and 06/2014, were retrospectively analyzed. PAH was defined as mean pulmonary
      arterial pressure (mPAP) of >=25mmHg or tricuspid regurgitation jet velocity of
      >=3.5m/s. RESULTS: In 228 patients (median age at shunt closure 4.0years, range
      0.5-69) and 174 complete follow-up data (median follow-up 3.7years, range 0.5
      39.4), 9 patients needed pulmonary vasodilator therapy after shunt closure, 4 of
      them temporarily for up to 79months. Three patients are still on vasodilator
      treatment 1, 2.6 and 6years after surgery, other two were lost to follow-up.
      Another 6 patients with preoperatively borderline hemodynamics due to elevated
      mPAP and pulmonary vascular resistance, recovered well without signs of
      postoperative PAH. CONCLUSION: With the current practice for safe late VSD
      closure, PAH is very rare at least in the first years of follow-up. In most
      patients with perioperative PAH, this condition appears to be transient and shows
      good response on pulmonary vasodilator treatment.

PMID- 27866023
TI  - Direct and adjusted indirect comparisons of perioperative mortality after
      sutureless or rapid-deployment aortic valve replacement versus transcatheter
      aortic valve implantation.
AB  - OBJECTIVES: To determine which procedure, aortic valve replacement (AVR) with a
      sutureless or rapid-deployment prosthesis (SL-AVR) or transcatheter aortic valve
      implantation (TAVI), achieves better perioperative survival for severe aortic
      stenosis (AS), we conducted direct-comparison meta-analyses (DC-MAs) and an
      adjusted indirect-comparison meta-analysis (IDC-MA). METHODS: We searched
      MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through
      April 2016. Eligible studies were randomized controlled trials (RCTs) and
      propensity-score matched (PSM) studies. We performed a DC-MA-[A] of SL-AVR versus
      TAVI, a DC-MA-[B] of SL-AVR versus conventional AVR (C-AVR), and a DC-MA-[C] TAVI
      versus C-AVR. Then, we computed a IDC-MA-[A'] of TAVI versus SL-AVR from the
      results of the DC-MA-[B] and the DC-MA-[C]. RESULTS: We identified 6 RCTs and 30
      PSM studies enrolling a total of 15,887 patients. The 3 DC-MAs demonstrated
      significantly lower perioperative (30-day or in-hospital) all-cause mortality
      after SL-AVR than after TAVI (odds ratio [OR], 0.48; 95% confidence interval
      [CI], 0.28 to 0.80; p=0.005) and no significant differences between SL-AVR and C
      AVR (OR, 1.07; 95% CI, 0.60 to 1.94; p=0.81) and between TAVI and C-AVR (1.07;
      95% CI, 0.90 to 1.27; p=0.45). The computed IDC-MA-[A'] indicated no significant
      difference in mortality between SL-AVR and TAVI (1.01; 95% CI, 0.54 to 1.86).
      Combining the results of the DC-MA-[A] and IDC-MA [A'] showed significantly lower
      mortality after SL-AVR than after TAVI (OR, 0.65; 95% CI, 0.44 to 0.97; p=0.03).
      CONCLUSIONS: For patients with severe AS, SL-AVR may achieve better perioperative
      survival than TAVI.

PMID- 27866022
TI  - Novel approaches toward the generation of bioscaffolds as a potential therapy in
      cardiovascular tissue engineering.
AB  - Cardiovascular disease associated with myocardial infarction (MI) is among the
      leading causes of mortality worldwide, in part, due to the limited regenerative
      capacity of tissues. Although various approaches have been employed to generate
      bioartificial myocardial tissues, including surgical reconstruction and the use
      of biosynthetic or biological cell-free grafts, many challenges still remain.
      Natural biomaterials based on decellularization have made significant inroads
      into the development of favorable biomatrices for myocardial tissue regeneration.
      This process occurs with the concept of removing whole cellular contents, while
      preserving the extracellular matrix components and all the necessary features of
      native tissues. Furthermore, acellular-derived matrices serve to stimulate
      proliferation and recruitment of endothelial cells by providing proliferation
      signals to cells. This review highlights a novel approach to generate natural
      three dimensional myocardial scaffolds for clinical applications.

PMID- 27866024
TI  - Comparison of prognostic significance of mean platelet volume/platelet count with
      GRACE for long-term prognosis in patients with non-ST-segment elevation
      myocardial infarction undergoing percutaneous coronary intervention.
AB  - BACKGROUND: Mean platelet volume to platelet count ratio (MPV/P ratio) has been
      demonstrated to be a predictor of adverse outcome in patients with non-ST-segment
      elevation myocardial infarction (NSTEMI). We aimed to assess whether MPV/P ratio
      is a useful marker to predict long-term prognosis in NSTEMI patients undergoing
      PCI. Moreover, the prognostic accuracy of MPV/P ratio was compared with MPV and
      GRACE score. METHODS: In a retrospective cohort study, according to the baseline
      MPV/P values, 887 consecutive NSTEMI patients undergoing PCI were divided into
      two groups: the high MPV/P group (n=296, MPV/P >=0.054) and the low MPV/P group
      (n=591, MPV/P<0.054). Clinical endpoints were all-cause mortality and all-cause
      mortality/nonfatal reinfarction. RESULTS: Multivariate analysis showed that high
      MPV/P was an independent predictor of all-cause mortality [HRs: 1.973, 95% CI:
      1.528-2.549, P<0.001], and all-cause mortality/nonfatal myocardial reinfarction
      [HRs: 1.289, 95% CI: 1.181-1.408, P<0.001]. MPV/P ratio has good accuracy for
      predicting clinical endpoints. The discriminatory performance of MPV/P ratio was
      similar to GRACE score but better than MPV (for all-cause mortality: MPV/P vs.
      GRACE: z=0.205, p=0.837; MPV/P vs. MPV: z=2.677, p=0.008; GRACE vs. MPV: z=3.017,
      p=0.003; for all-cause mortality/nonfatal myocardial: MPV/P vs. GRACE: z=1.098,
      p=0.272; MPV/P vs. MPV: z=4.026, p<0.001; GRACE vs. MPV: z=4.962, p<0.001).
      CONCLUSIONS: MPV/P ratio was similar to GRACE score but better than MPV for
      predicting all-cause mortality and all-cause mortality/nonfatal myocardial
      reinfarction in NSTEMI patients undergoing PCI. However, MPV/P ratio is easier to
      calculate than GRACE score.

PMID- 27866025
TI  - The adverse impact of obesity on heart rate variability is modified by a NFE2L2
      gene variant: The SAPALDIA cohort.
AB  - BACKGROUND: Overweight has been associated with an increase in inflammatory
      markers and with an imbalance in the autonomic nervous system, such as a decrease
      in heart rate variability (HRV). In this study we aimed to investigate the
      modifying effect of a genetic variation in a major anti-inflammatory marker gene,
      NFE2L2, on the relationship between overweight and HRV. METHODS: We analyzed
      participants of the SAPALDIA cohort aged 50years and older, twice in 2002/2003
      (N=1472) and 2010/2011 (N=1235). We included persons with valid genotype data,
      who underwent ambulatory 24-h electrocardiogram monitoring, and reported on
      medical history and lifestyle. The association between HRV and BMI, measured as
      standard deviation of normal-to-normal intervals (SDNN) by BMI and the modifying
      effect of the cardiovascular health-related NFE2L2 gene variant rs2364723 were
      tested, applying multivariable mixed linear regression models. RESULTS: We found
      study participants with overweight (BMI>25) over two follow-up surveys 10years
      apart to have a negative association between SDNN, calculated as geometric means,
      with BMI. The examined NFE2L2 variant sustainably modified (pinteraction=0.014)
      the found inverse association between a BMI increment and SDNN, causing a
      stronger decrement in SDNN for participants with the CC genotype (-20.7%; 95%
      confidence interval: -12.33 to -28.28) compared with participants carrying the GC
      (-7.43; 95%CI: -3.56 to -11.15) or GG (-11.26%; 95%CI: -7.68 to -14.7) genotype,
      estimated for the difference from the 90th to the 10th percentile of BMI by the
      NFE2L2 variant. CONCLUSIONS: Our results are consistent with the hypothesis that
      overweight decreases heart rate variability through inflammatory processes.

PMID- 27866026
TI  - Survival and cardiovascular events after coarctation-repair in long-term follow
      up (COAFU): Predictive value of clinical variables.
AB  - OBJECTIVE: Long-term sequelae and events after coarctation repair are well
      described. However, the predictive value of variables from clinical follow-up
      investigation for late events and survival has rarely been investigated. METHODS:
      All patients who participated in the prospective cross-sectional COALA Study in
      2000 with a structural clinical investigation including blood pressure
      measurement and symptom-limited exercise test were contacted for reevaluation of
      survival, current clinical status and major cardiovascular events. RESULTS: Of
      273 eligible patients, 209 were available for follow-up. Nine patients had died
      at a median age of 46years (range 30-64years), five of them due to cardiovascular
      complications. Late mortality after surgical intervention was 5.7% with a median
      age of 41years (range 16-64years). Twenty-five patients had a major
      cardiovascular event: 12 had procedures at the aortic valve or aortic arch, 8 had
      procedures for restenosis, 2 had endocarditis, 2 had a cerebrovascular insult and
      1 an aortic dissection. The presence of bicuspid aortic valve (p=0.009), brachial
      ankle blood pressure gradient >20mmHg (p<0.001) and reduced left ventricular
      function (p=0.002) correlated with major cardiovascular events. CONCLUSION:
      Surgical correction of coarctation of the aorta shows fairly low mortality in the
      long-term follow-up. Late morbidities include recoarctation, but also the
      consequences of the hemodynamics produced by a congenital bicuspid aortic valve,
      presence of which is predictive for aortic valve procedures: however the
      predictive value of clinical variables is limited.

PMID- 27866027
TI  - Cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors in
      patients with type II diabetes mellitus: A meta-analysis of placebo-controlled
      randomized trials.
AB  - BACKGROUND: The impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on
      cardiovascular outcomes in patients with type II diabetes mellitus (DM) is not
      well established. METHODS: We searched electronic databases from inception
      through July 2016 for randomized, placebo-controlled trials, involving SGLT-2
      inhibitors. Fixed-effects summary odds ratios (OR) were constructed using Peto
      model. RESULTS: Eighty-one trials with a total of 37,195 patients were included.
      The mean follow-up was 89weeks. Compared with placebo, SGLT-2 inhibitors were
      associated with a lower risk of all-cause mortality (OR 0.72; 95% CI 0.59-0.86;
      P<0.001), cardiovascular mortality (OR 0.67; 95% CI 0.53-0.84; P=0.001), and
      heart failure (OR 0.67; 95% CI 0.51-0.87; P=0.003), but a similar risk of
      myocardial infarction (OR 0.89; 95% CI 0.74-1.09; P=0.29) and stroke/transient
      ischemic attack (OR 1.09; 95% CI 0.87-1.37; P=0.47). The reduction in all-cause
      mortality was noticed with empagliflozin (OR 0.66; 95% CI 0.54-0.81; P<0.001),
      but not with other SGLT-2 inhibitors (ORdapagliflozin 1.37; 95% CI 0.71-2.62;
      P=0.35; ORcanagliflozin 0.82; 95% CI 0.41-1.68; P=0.59; ORluseogliflozin 4.6; 95%
      CI 0.07-284.25; P=0.47; and ORipragliflozin 4.73; 95% CI 0.08-283.14; P=0.46)
      (Pinteraction=0.19). Potential harm was observed with dapagliflozin on
      cardiovascular mortality (OR 2.15, 95% CI 0.92-5.04, P=0.08). CONCLUSIONS: In
      patients with type II DM, SGLT-2 inhibitors appeared to reduce both all-cause and
      cardiovascular mortality, primarily due to reduction in the risk of heart
      failure. The benefit was only seen with empagliflozin. There was suggestion of
      potential harm with dapagliflozin, thus future trials are needed to ascertain the
      cardiovascular safety of other agents in this class.

PMID- 27866028
TI  - Lifetime competing risks between coronary heart disease mortality and other
      causes of death during 50years of follow-up.
AB  - OBJECTIVES: To study coronary heart disease (CHD) death versus 11 other causes of
      death using the cumulative incidence function (CIF) and the competing risks
      procedures to disentangle the differential role of risk factors for different end
      points. MATERIAL AND METHODS: Standard Cox and Fine-Gray models among 1712 middle
      aged men were compared during 50years of follow-up. CHD death was the primary
      event, while deaths from 11 selected causes, mutually exclusive from the primary
      end-point, were considered as secondary events. Reverse solutions were also
      performed. We considered 10 selected risk factors. RESULTS: CHD death risk was
      the second highest among 12 mostly specific causes of death. Some risk factors
      were specific: serum cholesterol for CHD death whereas, systolic blood pressure,
      cigarette smoking and age may have a differential role in other causes of death.
      Application of the Fine-Gray model based on CIF enabled to dissect, at least in
      part, the respective role that baseline covariates may have to segregate the
      probabilities of two types of death in contrast from each other. They also point
      to the absence of contributing significance for some of the selected risk factors
      and this calls for a parsimonious approach in predictions. CONCLUSIONS: The
      relative rarity of competing risk challenges when defining the risk factors role
      at long-term needs now be corrected since we have clearly shown, with Fine-Gray
      model, at direct or reverse use, that comparing different end-points heavily
      influences the risk factor predictive capacity.

PMID- 27866029
TI  - Understanding the structural features of symptomatic calcific aortic valve
      stenosis: A broad-spectrum clinico-pathologic study in 236 consecutive surgical
      cases.
AB  - BACKGROUND: With age, aortic valve cusps undergo varying degrees of sclerosis
      which, sometimes, can progress to calcific aortic valve stenosis (AVS). To
      perform a retrospective clinico-pathologic investigation in patients with
      calcific AVS. METHODS: We characterized and graded the structural remodeling in
      236 aortic valves (200 tricuspid and 36 bicuspid) from patients with calcific AVS
      (148 males; average 72years); possible relationships between
      general/clinical/echocardiographic characteristics and the histopathologic
      changes were explored. Twenty autopsy aortic valves served as controls. In 40
      cases, we also tested the immunohistochemical expression of metalloproteinases
      and cytokines, and characterized the inflammatory infiltrate. In 5 cases, we
      cultured cusp stem cells and explored their potential to differentiate into
      osteoblasts/adipocytes. RESULTS: AVS cusps showed structural remodeling as severe
      fibrosis (100%), calcific nodules (100%), neoangiogenesis (81%), inflammation
      (71%), bone metaplasia with or without hematopoiesis (6% and 53%, respectively),
      adipose metaplasia (16%), and cartilaginous metaplasia (7%). At multivariate
      analysis, AVS degree and interventricular septum thickness were the only
      predictors of remodeling (barring inflammation). All the tested
      metalloproteinases (except MMP-13) and cytokines were expressed in AVS cusps.
      Inflammation mainly consisted of B and T lymphocytes (CD4+/CD8+ cell ratio 3:1)
      and plasma cells. AVS changes were mostly different from typical atherosclerosis.
      Cultured mesenchymal cusp stem cells could differentiate into
      osteoblasts/adipocytes. CONCLUSIONS: Structural remodeling in AVS is peculiar and
      considerable, and is related to the severity of the disease. However, the
      different newly formed tissues-where "valvular interstitial cells" play a key
      role-and their well-known slow turnover suggest a reverse structural remodeling
      improbable.

PMID- 27866030
TI  - Diagnostic accuracy of CT for the detection of left ventricular myocardial
      fibrosis in various myocardial diseases.
AB  - PURPOSE: To evaluate the diagnostic accuracy of computed tomography (CT) for the
      detection of myocardial fibrosis, we compared the frequency of abnormal late
      enhancement (LE) in left ventricular myocardium (LVM) on CT with that on
      gadolinium-enhanced cardiac magnetic resonance (CMR) in patients with various
      myocardial diseases. METHODS: Fifty-six patients with suspected various
      myocardial diseases (19 with hypertrophic cardiomyopathy, 3 with cardiac
      amyloidosis, 3 with post myocarditis, 2 with dilated cardiomyopathy, 2 with
      cardiac sarcoidosis, 2 with cardiac tumor, 2 with previous myocardial infarction,
      2 with hypertensive heart disease) underwent 1.5-T CMR and cardiac CT within
      2months without clinical accidents. RESULTS: LE on LVM was detected in 31 and 31
      patients on CT and CMR, respectively, and in 192 and 197 LVM segments on CT and
      CMR, respectively, among a total of 952 LVM segments. The sensitivity,
      specificity, positive and negative predictive values, and consistency for
      detection of LE on CT in comparison with CMR were 90, 89, 90, 89 and 89%,
      respectively, on patient-based analysis, and 67, 92, 68, 91 and 87%,
      respectively, on segment-based analysis. Inter-observer agreement for detection
      of LE on CT was 0.71 (kappa coefficient), and it was significantly lower than
      that on CMR (0.82) on segment-based analysis (P<0.05). CONCLUSIONS: Compared with
      CMR, diagnostic accuracy of CT for the evaluation of LE in LVM in patients with
      myocardial diseases was relatively higher on patient-based analysis, but was
      limited on segment-based analysis, and the inter-observer agreement on CT was
      significantly lower than that on CMR.

PMID- 27866031
TI  - Aortopathy in adults with tetralogy of Fallot has a negative impact on the left
      ventricle.
AB  - BACKGROUND: Aortic pressure wave reflection is significantly elevated in patients
      with congenital heart disease, even in children. Excessive aortic pressure wave
      reflection provokes cardiovascular events. AIM: To assess the influences of the
      enhanced pressure wave reflection on the left ventricle (LV) in adults with
      repaired tetralogy of Fallot (TOF). METHODS: Prospectively, 51 consecutive adults
      with repaired TOF (35.5+/-11.6yrs., 25 males) were enrolled and non-invasively
      assessed the pressure wave reflection using HEM 9000AI. A surrogate maker of the
      aortic pressure wave reflection, radial augmentation index (rAI) was calculated
      as reflection wave divided by ejection wave. We also evaluated LV function using
      echocardiography and magnetic resonance images. Patients were divided into two
      groups: group A with rAI?1SD and group B with rAI<1SD. RESULTS: The mean rAI in
      repaired TOF was 76.9+/-14.3%. In group A, indexed ascending aortic diameter, LV
      global longitudinal strain (GLS), LV global circumferential strain (GCS), LV
      early diastolic strain rate (SR), LV E/A, LV e' were significantly higher than
      them in group B. The indexed ascending aortic diameter significantly correlated
      with rAI (r=0.31, P<0.05). On univariate logistic analysis, body surface area,
      indexed ascending aortic diameter, GLS, GCS, early diastolic SR, LV E/A, LV mass
      index and creatinine were predictive factors of rAI?1SD. On multivariate logistic
      analysis, LV E/A was the most significant predictive factor of rAI?1SD (Odds
      ratio 0.044, 95%CI 0.002-0.98 and P<0.05). CONCLUSIONS: Aortic pressure wave
      reflection in adults with repaired TOF has a negative impact on LV function,
      particularly on diastolic function.

PMID- 27866032
TI  - Prediction of peak oxygen uptake in patients with Chagas heart disease: Value of
      the Six-minute Walk Test.

PMID- 27866033
TI  - Bone scintigraphy for the diagnosis of the responsible level of osteoporotic
      vertebral compression fractures in percutaneous balloon kyphoplasty.
AB  - OBJECTIVES: This study was to investigate the efficacy of bone scintigraphy in
      order to diagnose the correct level of vertebral compression fractures (VCF) for
      the severe back pain before balloon kyphoplasty (BKP) was performed. PATIENTS AND
      METHODS: A total of 30 consecutive patients were treated with BKP for 38 times
      since May 2012. Eleven patients had acute multi-level VCFs. Bone scintigraphy was
      performed preoperatively except for the first case and the case with a chronic
      course and the level responsible for the pain was defined with bone scintigraphy.
      The responsible level of acute single level VCF was easily diagnosed with T1, T2,
      and fat sat T2 but the responsible level of acute multi-level VCFs was not easily
      determined. BKP was performed at the most accumulated level on bone scintigraphy
      and the preoperative and postoperative Visual analogue score (VAS) scores were
      researched with questionnaire postoperatively. RESULTS: BKP was effective in
      relief of pain at the most accumulated level on bone scintigraphy. Preoperative
      VAS score (average 8.6) was significantly improved at post-ope day1 (average
      3.9), at discharge (average 2.4) and at 1 month after discharge (average 2.1).
      New symptomatic VCFs after the first treatment occurred in 5 patients at an
      adjacent level in 3 and twice in 2 of 5 and additional BKP was effective in each
      patient. CONCLUSIONS: The correct level of symptomatic VCF in the patients with
      acute multi-level VCFs should be diagnosed to achieve good clinical results. In
      this study, we showed that bone scintigraphy is very useful in diagnosing the
      proper level for BKP in addition to CT and MRI.

PMID- 27866035
TI  - A unique presentation of ectopic thyroid, a case report.
AB  - INTRODUCTION: This case presents a painful ectopic thyroid, an unusual
      presentation, in an atypical location. The patient's history of an ingested fish
      bone, her acute presentation, and inconclusive imaging, made this case a
      diagnostic dilemma. PRESENTATION OF CASE: 61-year-old female presented with
      acutely worsening history of left throat pain and dysphagia after swallowing a
      fish bone. CT scan showed a foreign body in the anterior wall of the cervical
      esophagus. EGD studies were inconclusive. Surgical exploration identified and
      excised a multinodular cystic lesion without connection to esophageal lumen.
      Pathology described multinodular thyroid parenchyma with chronic inflammation and
      no evidence of malignancy. No foreign body was located. DISCUSSION: Based on the
      patient's history, imaging, and acute presentation, an esophageal perforation
      with abscess formation was the most likely diagnosis. Surgical exploration was
      the necessary intervention for this patient's acute symptoms as both a diagnostic
      and therapeutic tool. The diagnosis of ectopic thyroid tissue from pathology of
      the excised cystic lesion was unexpected, as the location of tissue and the
      painful presentation are not typical characteristics of ectopic thyroid tissue.
      Management of the this case illustrates the dilemma faced in determining the
      appropriate work up for a patient, without compromising the patient's safety.
      CONCLUSION: Though painful presentation and this case's location are rare,
      ectopic thyroid tissue should be included in the differential diagnosis of point
      tenderness with an associated lesion on imaging.

PMID- 27866034
TI  - Micro vs. macrodiscectomy: Does use of the microscope reduce complication rates?
AB  - OBJECTIVE: A single level discectomy is one of the most common procedures
      performed by spine surgeons. While some practitioners utilize the microscope,
      others do not. We postulate improved visualization with an intraoperative
      microscope decreases complications and inferior outcomes. METHODS: A multicenter
      surgical registry was utilized for this retrospective cohort analysis. Patients
      with degenerative spinal diagnoses undergoing elective single level discectomies
      from 2010 to 2014 were included. Univariate analysis was performed comparing
      demographics, patient characteristics, operative data, and outcomes for
      discectomies performed with and without a microscope. Multivariable logistic
      regression analysis was then applied to compare outcomes of micro- and
      macrodiscectomies. RESULTS: Query of the registry yielded 23,583 patients meeting
      inclusion criteria. On univariate analysis the microscope was used in a greater
      proportion of the oldest age group as well as Hispanic white patients. Patients
      with any functional dependency, history of congestive heart failure, chronic
      corticosteroid use, or anemia (hematocrit<35%) also had greater proportions of
      microdiscectomies. Thoracic region discectomies more frequently involved use of
      the microscope than cervical or lumbar discectomies (25.0% vs. 16.4% and 13.0%,
      respectively, p<0.001). Median operative time (IQR) was increased in microscope
      cases [80min (60, 108) vs. 74min (54, 102), p<0.001]. Of the patients that
      required reoperation within 30days, 2.5% of them had undergone a microdiscectomy
      compared to 1.9% who had undergone a macrodiscectomy, p=0.044. On multivariable
      analysis, microdiscectomies were more likely to have an operative time in the top
      quartile of discectomy operative times, >=103min (OR 1.256, 95% CI 1.151-1.371,
      p<0.001). In regards to other multivariable outcome models for any complication,
      surgical site infection, dural tears, reoperation, and readmission, no
      significant association with microdiscectomy was found. CONCLUSIONS: The use of
      the microscope was found to significantly increase the odds of longer operative
      time, but not influence rates of postoperative complications. Thus, without
      evidence from this study that the microscope decreases complications, the use of
      the microscope should be at the surgeon's discretion, validating the use of both
      macro and micro approaches to discectomy as acceptable standards of care.

PMID- 27866036
TI  - Idiopathic chylous ascites simulating acute appendicitis: A case report and
      literature review.

PMID- 27866037
TI  - Preoperative preparation of a patient with grade II leg Lymphedema for his third
      hip replacement surgery.
AB  - INTRODUCTION: The treatment of lymphedema remains a challenge to modern medicine,
      due to the characteristics of the disease. CASE PRESENTATION: Report on the case
      of a 75-year-old patient with lower limb lymphedema for treatment prior to
      surgery. At age 45, he made the first hip replacement surgery in the left leg.
      One year later he performed the same surgery on the right leg. At that time his
      legs had slight ankle edema mainly of the left leg and the entire left leg was
      affected by lymphedema. At 68 years old the patient returned to the surgeon, who
      indicated a third surgery to replace the left hip prosthesis. The patient was
      evaluated by bioimpedance, which measured the volumes of right and left legs at
      5.52 and 7.24l, respectively. Five days of intensive treatment were proposed
      using Mechanical Lymphatic Therapy (RAGodoy(r)), Manual Lymphatic Therapy and
      compression therapy with a grosgrain stocking for 24h per day. On the fifth day,
      there was significant improvement in the volume (right leg 4.45l and left leg
      5.57l). DISCUSSION: In this case report intensive treatment was used to reduce
      the volume of leg edema prior to a surgery to replace a hip prosthesis in a
      patient with grade II leg lymphedema. Small positive and negative changes, which
      are common in the evolution of this type of case but the end result was a total
      reduction of the edema. CONCLUSION: The patient underwent surgery to replace the
      prosthesis after total reduction of edema.

PMID- 27866038
TI  - Separating content-specific retrieval from post-retrieval processing.
AB  - According to cortical reinstatement accounts, neural processes engaged at the
      time of encoding are re-engaged at the time of memory retrieval. The temporal
      precision of event-related potentials (ERPs) has been exploited to assess this
      possibility, and in this study ERPs were acquired while people made memory
      judgments to visually presented words encoded in two different ways. There were
      reliable differences between the scalp distributions of the signatures of
      successful retrieval of different contents from 300 to 1100 ms after stimulus
      presentation. Moreover, the scalp distributions of these content-sensitive
      effects changed during this period. These findings are, to our knowledge, the
      first demonstration in one study that ERPs reflect content-specific processing in
      two separable ways: first, via reinstatement, and second, via downstream
      processes that operate on recovered information in the service of memory
      judgments.

PMID- 27866039
TI  - Sleep EEG maps the functional neuroanatomy of executive processes in adolescents
      born very preterm.
AB  - Executive function deficits are among the most frequent sequela of very preterm
      birth but the underlying neuronal mechanisms are not fully understood. We used
      high-density electroencephalography (EEG) recordings during sleep to assess
      alterations in the functional neuroanatomy of executive processes in adolescents
      born very preterm. The topographical distribution of sleep slow wave activity
      (SWA; 1-4.5 Hz EEG power) has previously been used to map cognitive abilities and
      is known to reflect the intensity of the prior use of the respective neuronal
      networks. We assessed 38 adolescents born before 32 weeks of gestation [age at
      assessment: 12.9 (SD: 1.7), range: 10.6-16.7 years] and 43 term-born peers [13.1
      (2.0), 10.0-16.9]. Executive function abilities were quantified with a composite
      score derived from a comprehensive task battery. All-night high-density EEG (128
      electrodes) was recorded and SWA of the first hour of sleep was calculated.
      Abilities were significantly poorer in the very preterm compared to the term
      group, particularly, if the tasks demands were high (p < .01). The score was
      positively correlated with sleep SWA in a cluster of 15 electrodes over frontal
      and negatively in a cluster of 14 electrodes over central brain regions after
      controlling for age at assessment and correcting for multiple comparisons. Within
      the frontal cluster, sleep SWA was higher in very preterm compared to term-born
      participants when controlling for executive function performance and age at
      assessment (p = .02). No difference in SWA between very preterm and term-born
      participants was found for the central cluster (p = .29). Our results demonstrate
      a local increase of sleep SWA over brain regions associated with executive
      processes in adolescents born very preterm compared to similarly performing term
      born peers. Thus, sleep SWA seems to map the higher effort needed for executive
      function tasks in adolescents born very preterm.

PMID- 27866040
TI  - In vitro fermentation of different fructo-oligosaccharides by Bifidobacterium
      strains for the selection of synbiotic combinations.
AB  - The use of selected probiotics, prebiotics and/or synbiotics, constitute an
      interesting dietary strategy for intestinal microbiota modulation in case of
      dysbiosis. Species of the genus Bifidobacterium are among the most currently used
      probiotics for human consumption since they have shown beneficial effects in the
      prevention and treatment of some disorders. Bifidobacteria are saccharolytic
      microorganisms, but their ability to use different carbohydrates varies among
      strains. In this study, we investigate the utilization of three prebiotic
      substrates (two different short-chain fructo-oligosaccharides [scFOS] and inulin)
      by strains of Bifidobacterium, in order to determine the synbiotic potential of
      the different probiotic/prebiotic combinations. Batch culture fermentations from
      six Bifidobacterium strains (Bifidobacterium longum IPLA20021, B. longum
      IPLA20022, Bifidobacterium animalis IPLA20031, B. animalis IPLA20032, B. animalis
      IPLA20020 and B. animalis Bb12) were carried out in the presence of inulin or
      scFOS (Synergy or Actilight), or glucose, as carbon source. Bifidobacteria levels
      were quantified by plate counting. The pH and production of organic acids in the
      different batch-culture fermentations were also determined. Our results showed
      that all the studied strains of B. animalis and B. longum were able to utilize
      scFOS but not inulin. The use of scFOS as carbon source affected the pattern of
      metabolite's production, when compared with cultures carried out in glucose,
      particularly in the case of B. longum. The results indicated that the scFOS are
      well suited to be used in combination with B. animalis or B. longum strains for
      the development of synbiotic foods or food supplements.

PMID- 27866043
TI  - Sensory processing disorders in children with cerebral palsy.
AB  - OBJECTIVE: To evaluate sensory processing in children with CP using the Sensory
      Profile questionnaire and to compare results with the ones of children with
      typical development (TD). METHODS: We assessed sensory processing of 59 TD
      children and 43 CP children using the Sensory Profile, a standardized parent
      reporting measure that records children's responses to sensory events in daily
      life. Mann-Whitney test was used to compare the results of sensory processing
      evaluation among the groups. Bonferroni correction was applied. RESULTS: We found
      differences in sensory processing between groups in 16 out of the 23 categories
      evaluated in the Sensory Profile. CONCLUSION: Our results pointed out to the
      existence of disturbances in the processing of sensory information in CP. Based
      on the importance of the sensory integration process for motor function, the
      presence of such important disturbances draw the attention to the implementation
      of sensory therapies which improve function in these children.

PMID- 27866041
TI  - Study of the bacterial diversity of foods: PCR-DGGE versus LH-PCR.
AB  - The present study compared two culture-independent methods, polymerase chain
      reaction denaturing gradient gel electrophoresis (PCR-DGGE) and length
      heterogeneity polymerase chain reaction (LH-PCR), for their ability to reveal
      food bacterial microbiota. Total microbial DNA and RNA were extracted directly
      from fourteen fermented and unfermented foods, and domain A of the variable
      regions V1 and V2 of the 16S rRNA gene was analyzed through LH-PCR and PCR-DGGE.
      Finally, the outline of these analyses was compared with bacterial viable counts
      obtained after bacterial growth on suitable selective media. For the majority of
      the samples, RNA-based PCR-DGGE revealed species that the DNA-based PCR-DGGE was
      not able to highlight. When analyzing either DNA or RNA, LH-PCR identified
      several lactic acid bacteria (LAB) and coagulase negative cocci (CCN) species
      that were not identified by PCR-DGGE. This phenomenon was particularly evident in
      food samples with viable loads<5.0 Logcfug-1. Furthermore, LH-PCR was able to
      detect a higher number of peaks in the analyzed food matrices relative to species
      identified by PCR-DGGE. In light of these findings, it may be suggested that LH
      PCR shows greater sensitivity than PCR-DGGE. However, PCR-DGGE detected some
      other species (LAB included) that were not detected by LH-PCR. Therefore, certain
      LH-PCR peaks not attributed to known species within the LH-PCR database could be
      solved by comparing them with species identified by PCR-DGGE. Overall, this study
      also showed that LH-PCR is a promising method for use in the food microbiology
      field, indicating the necessity to expand the LH-PCR database, which is based, up
      to now, mainly on LAB isolates from dairy products.

PMID- 27866046
TI  - Changes in depression among older adults in China: A latent transition analysis.
AB  - BACKGROUND: Depression in late life is an important public health problem in
      developing countries. It is timely to investigate stability and transition
      patterns of depressive symptom subtypes. METHODS: Longitudinal data were used
      from the China Health and Retirement Longitudinal Study (CHARLS). A total of 853
      women and 930 men aged 60-96 years were recruited. Latent class and latent
      transition analysis (LCA/LTA) were used to identify meaningful subgroups,
      transitions between those classes across time, and baseline demographic features
      that help to predict and design tailored interventions. RESULTS: Three depression
      subgroups were identified: Class 1 was labeled "Mild Depression"; Class 2 was
      labeled "Severe Depression" and class 3 was labeled "Lack of Positive Affect". A
      predominant tendency for stability appeared rather than change, meanwhile
      individual in Mild Depression and Severe Depression latent status both had a high
      probability to convert to the Lack of Positive Affect latent status. Social
      activities played a significant role in buffering the effect of depression, while
      individuals with chronic diseases, having difficulty with ADLs and smoking might
      be at-risk groups. LIMITATIONS: The limitations of the present study were
      inherent limitation in the LTA model and some small proportion of transitions.
      CONCLUSIONS: This study demonstrated a transition pattern in older adult
      depression within a person-centered approach. Differential treatment effects were
      found across baseline depression class, suggesting the benefit for tailored
      intervention programs to improve depression outcomes among older adults.

PMID- 27866044
TI  - Alternative splicing of SMPD1 coding for acid sphingomyelinase in major
      depression.
AB  - BACKGROUND: Major depressive disorder (MDD) is a psychiatric disorder
      characterized by key symptoms that include depressed mood and a loss of interest
      and pleasure. A recently developed pathogenic model of MDD involves disturbed
      neurogenesis in the hippocampus, where the acid sphingomyelinase (ASM)/ceramide
      system plays an important role and is proposed as a molecular target for
      antidepressant action. Because alternative splicing of SMPD1 mRNA, coding for
      ASM, is relevant for the regulation of ASM enzymatic activity, we investigated
      the frequency of alternatively spliced ASM isoforms in peripheral blood cells of
      MDD patients versus healthy controls. METHODS: Because the full-length transcript
      variant 1 of SMPD1 (termed ASM-1) is the only known form within the splicing
      pattern that encodes an enzymatically fully active ASM, we determined a fraction
      of splice isoforms deviating from ASM-1 using PCR amplification and capillary
      electrophoresis with laser-induced fluorescence analysis. RESULTS: ASM
      alternative splicing events occurred significantly less frequently in MDD
      patients compared to healthy subjects. After 5 days of antidepressant treatment,
      the frequency of alternatively spliced ASM isoforms decreased in those patients
      who were treated with a functional inhibitor of ASM activity (FIASMA) but
      remained constant in MDD patients treated with other antidepressant drugs. This
      effect was more pronounced when healthy male volunteers were treated with the
      FIASMAs fluoxetine or paroxetine, in contrast to a placebo group. LIMITATIONS:
      Patients were treated with different antidepressant drugs, depending on
      individual parameters and disease courses. CONCLUSIONS: This study shows that the
      ASM alternative splicing pattern could be a biological target with diagnostic
      relevance and could serve as a novel biomarker for MDD.

PMID- 27866042
TI  - Carcinogenic effects of oil dispersants: A KEGG pathway-based RNA-seq study of
      human airway epithelial cells.
AB  - The health impacts of the BP oil spill are yet to be further revealed as the
      toxicological effects of oil products and dispersants on human respiratory system
      may be latent and complex, and hence difficult to study and follow up. Here we
      performed RNA-seq analyses of a system of human airway epithelial cells treated
      with the BP crude oil and/or dispersants Corexit 9500 and Corexit 9527 that were
      used to help break up the oil spill. Based on the RNA-seq data, we then
      systemically analyzed the transcriptomic perturbations of the cells at the KEGG
      pathway level using two pathway-based analysis tools, GAGE (generally applicable
      gene set enrichment) and GSNCA (Gene Sets Net Correlations Analysis). Our results
      suggested a pattern of change towards carcinogenesis for the treated cells marked
      by upregulation of ribosomal biosynthesis (hsa03008) (p=1.97E-13), protein
      processing (hsa04141) (p=4.09E-7), Wnt signaling (hsa04310) (p=6.76E-3),
      neurotrophin signaling (hsa04722) (p=7.73E-3) and insulin signaling (hsa04910)
      (p=1.16E-2) pathways under the dispersant Corexit 9527 treatment, as identified
      by GAGE analysis. Furthermore, through GSNCA analysis, we identified gene co
      expression changes for several KEGG cancer pathways, including small cell lung
      cancer pathway (hsa05222, p=9.99E-5), under various treatments of oil/dispersant,
      especially the mixture of oil and Corexit 9527. Overall, our results suggested
      carcinogenic effects of dispersants (in particular Corexit 9527) and their
      mixtures with the BP crude oil, and provided further support for more stringent
      safety precautions and regulations for operations involving long-term respiratory
      exposure to oil and dispersants.

PMID- 27866045
TI  - Corrigendum to "Prevalence and correlates of major depressive disorder and
      dysthymia in an eleven-year follow-up - Results from the Finnish Health 2011
      Survey" [J. Affect. Disord. 173 (2015) 73-80].

PMID- 27866047
TI  - Erratum to "GATA-4 regulation of myocardial survival in the preconditioned heart"
      [J. Mol. Cell. Cardiol. 37(6) (2004 Dec) 1195-1203].

PMID- 27866048
TI  - 7p22.1 microduplication syndrome: Refinement of the critical region.
AB  - 7p22.1 microduplication syndrome is mainly characterized by developmental and
      speech delay, craniofacial dysmorphisms and skeletal abnormalities. The minimal
      critical region includes two OMIM genes: ACTB and RNF216. Here, we report on a
      girl carrying the smallest 7p22.1 microduplication detected to date, contributing
      to the delineation of the clinical phenotype of the 7p22.1 duplication syndrome
      and to the refinement of the minimal critical region. Our patient shares several
      major features of the 7p22.1 duplication syndrome, including craniofacial
      dysmorphisms and speech and motor delay, but she also presents with renal
      anomalies. Based on present and published dup7p22.1 patients we suggest that
      renal abnormalities might be an additional feature of the 7p22.1 microduplication
      syndrome. We also pinpoint the ACTB gene as the key gene affecting the 7p22.1
      duplication syndrome phenotype.

PMID- 27866050
TI  - Boucher Neuhauser Syndrome - A rare cause of inherited hypogonadotropic
      hypogonadism. A case of two adult siblings with two novel mutations in PNPLA6.
AB  - Boucher Neuhauser Syndrome (BNS) is a rare clinical syndrome with autosomal
      recessive inheritance defined by early-onset ataxia, hypogonadism and
      chorioretinal dystrophy. We present two siblings diagnosed with BNS in late adult
      life identified with compound heterozygous state of two novel PNPLA6 mutations.
      Five healthy siblings were non- or heterozygous carriers of the mutations. The
      cases, which presented with ataxia in childhood and hypogonadotropic hypogonadism
      (HH), were diagnosed at age 17 and 25, respectively, when examined for delayed
      puberty. The youngest case, a 55-year old male, was referred to our department in
      2006 for evaluation of secondary causes of osteoporosis, which he developed
      despite adequate testosterone replacement therapy. The unusual medical history
      with childhood ataxia and hypogonadotropic hypogonadism lead to further
      examinations and eventually the diagnosis of BNS. The older sister of the proband
      also displayed the triad of ataxia, HH and chorioretinal dystrophy accompanied by
      cerebellar atrophy and in 2014, we found the mutations in PNPLA6. BNS is a rare
      cause of HH and secondary osteoporosis, but should be considered in patients
      presenting with one or more of the key features. Genetic screening is becoming
      increasingly available and inexpensive and accordingly this may be considered
      earlier and by broader indication in unusual phenotypic presentations. The
      increasing knowledge of causes for inherited diseases should extend the use of
      genetic screening, as the correct diagnosis will benefit the patients.

PMID- 27866049
TI  - Novel ELN mutation in a family with supravalvular aortic stenosis and
      intracranial aneurysm.
AB  - Pathogenic germline mutations in ELN can be detected in patients with
      supravalvular aortic stenosis. The mutation might occur de novo or be inherited
      following an autosomal dominant pattern of inheritance. In this report we
      describe a three-generation family suffering from supravalvular aortic stenosis,
      various other arterial stenoses, sudden death, and intracranial aneurysms. A
      frameshift mutation in exon 12, not described before, was detected in the
      affected family members. This report emphasises the importance of family history,
      genetic counselling, and demonstrates the great variability in the phenotype
      within a single SVAS family.

PMID- 27866051
TI  - Insights into structure and function of 30S Ribosomal Protein S2 (30S2) in
      Chlamydophila pneumoniae: A potent target of pneumonia.
AB  - The gene 30S ribosomal protein S2 (30S2) is identified as a potential drug and
      vaccine target for Pneumonia. Its structural characterization is an important to
      understand the mechanism of action for identifying its receptor and/or other
      binding partners. The comparative genomics and proteomics studies are useful for
      structural characterization of 30S2 in C. Pneumoniae using different
      bioinformatics tools and web servers. In this study, the protein 30S2 structure
      was modelled and validated by Ramachandran plot. It is found that the modelled
      protein under most favoured "core" region was 88.7% and overall G-factor
      statistics with average score was -0.20. However, seven sequential motifs have
      been identified for 30S2 with reference codes (PR0095, PF0038, TIGR01012,
      PTHR11489, SSF52313 and PTHR11489). In addition, seven structural highly
      conserved residues have been identified in the large cleft are Lys160, Gly161and
      Arg162 with volume 1288.83A3 and average depth of the cleft was 10.75A. Moreover,
      biological functions, biochemical process and structural constituents of ribosome
      are also explored. The study will be helped us to understand the sequential,
      structural, functional and evolutionary clues of unknown proteins available in C.
      Pneumoniae.

PMID- 27866052
TI  - Investigating dysregulated pathways in Staphylococcus aureus (SA) exposed
      macrophages based on pathway interaction network.
AB  - OBJECTIVE: This work aimed to identify dysregulated pathways for Staphylococcus
      aureus (SA) exposed macrophages based on pathway interaction network (PIN).
      METHODS: The inference of dysregulated pathways was comprised of four steps:
      preparing gene expression data, protein-protein interaction (PPI) data and
      pathway data; constructing a PIN dependent on the data and Pearson correlation
      coefficient (PCC); selecting seed pathway from PIN by computing activity score
      for each pathway according to principal component analysis (PCA) method; and
      investigating dysregulated pathways in a minimum set of pathways (MSP) utilizing
      seed pathway and the area under the receiver operating characteristics curve
      (AUC) index implemented in support vector machines (SVM) model. RESULTS: A total
      of 20,545 genes, 449,833 interactions and 1189 pathways were obtained in the gene
      expression data, PPI data and pathway data, respectively. The PIN was consisted
      of 8388 interactions and 1189 nodes, and Respiratory electron transport, ATP
      synthesis by chemiosmotic coupling, and heat production by uncoupling proteins
      was identified as the seed pathway. Finally, 15 dysregulated pathways in MSP
      (AUC=0.999) were obtained for SA infected samples, such as Respiratory electron
      transport and DNA Replication. CONCLUSIONS: We have identified 15 dysregulated
      pathways for SA infected macrophages based on PIN. The findings might provide
      potential biomarkers for early detection and therapy of SA infection, and give
      insights to reveal the molecular mechanism underlying SA infections. However, how
      these dysregulated pathways worked together still needs to be studied.

PMID- 27866053
TI  - LC-ESI-MS/MS evaluation of forced degradation behaviour of silodosin: In vitro
      anti cancer activity evaluation of silodosin and major degradation products.
AB  - Silodosin (SLD) a novel alpha1-adrenoceptor antagonist was subjected to forced
      degradation involving hydrolysis (acidic, alkaline and neutral), oxidative,
      photolysis and thermal stress, as per ICH specified conditions. The drug
      underwent significant degradation under hydrolytic (acidic, alkaline and neutral)
      and oxidative stress conditions whereas, it was found to be stable under other
      stress conditions. A rapid, precise, accurate and robust chromatographic method
      for the separation of the drug and its degradation products (DPs) was developed
      on a Fortis C18 analytical column (150*4.6mm, 5MUm) using 0.1% formic acid and
      acetonitrile as a mobile phase in gradient elution mode at a flow rate of
      1.0mL/min. A total of 5 (DP 1 to DP 5) hitherto unknown DPs were identified by LC
      ESI-TOF-MS/MS experiments and accurate mass measurements. The most probable
      mechanisms for the formation of DPs have been proposed based on a comparison of
      the fragmentation of the [M+H]+ ions of silodosin and its DPs. The major DPs (DP
      1 and DP 2) were isolated and evaluated for anticancer activity using PC3 (human
      prostate cancer) cell lines by MTT assay. The results revealed that silodosin, DP
      1 and DP 2 have potential anticancer activity with IC50 values (MUM) 72.74 (+/
      4.51), 25.21 (+/-2.36), and, 114.07 (+/-11.90) respectively.

PMID- 27866054
TI  - Comparison of miRNA signature versus conventional biomarkers before and after off
      pump coronary artery bypass graft.
AB  - Circulating levels of microRNAs (miRNAs) and their expression patterns are
      supposed to serve as signatures for diagnosis or prognosis of cardiovascular
      events. The present study aimed at determining if there is any correlation
      between the release pattern of 2 miRNAs and the plasma levels of conventional
      biomarkers cardiac troponin I (cTnI), creatine kinase (CK) and uric acid (UA) in
      patients undergoing their first off-pump coronary artery bypass graft (OCABG).
      Seventy OCABG patients (69% men, aged 59.2+/-8.2years) were enrolled.
      Emergencies, re-operations, abnormal preoperative serum cTnI and combined
      procedures were excluded from this study. Pre-operative mean ejection fraction
      was 45.8+/-8.6%, the average number of grafts was 3+/-0.87/patient, and the
      internal mammary artery was used for all. Beside conventional clinical assays, we
      performed real-time quantitative PCR to analyze the circulating levels of miR
      155, miR-126 and miR-499 at 1day before surgery as well as 4days after surgery.
      Importantly, there was no report of myocardial infarction in our patients, pre-
      or post-operatively. In contrast to conventional biomarkers cTnI and CK,
      circulating levels of miRNAs decreased significantly (P<0.01) after
      revascularization surgery. A significant positive correlation was seen between
      the cTnI and miR-499 (r~0.53, P<0.01) and between miR-126 and UA (r~0.5, P<0.01).
      Time course study of circulating miR-499, miR-126 and miR-155 in cardiac surgery
      clarified their advantage and correlations to the traditional biomarkers cTnI,
      total CK, CK-MB and UA. Our results suggest that this signature is a novel, early
      biomarker which indicates myocardial ischemia in cardiac surgery. It could be
      postulated that the application of these miRNAs may be considered for monitoring
      of response to pharmacological interventions aimed at reducing cardiac ischemia,
      especially in OCABG candidates.

PMID- 27866055
TI  - Microstructure and nanoindentation analyses of low-temperature aging on the
      zirconia-porcelain interface.
AB  - The aim of the present study was to investigate the effects of low-temperature
      aging on the micro-mechanical and micro-structural properties of zirconia
      porcelain interface. In total, thirty-three Y-TZP zirconia blocks were fabricated
      by using CAD/CAM technology, veneered with porcelains. Specimens were submitted
      to low-temperature aging in an autoclave at 134 degrees C, additional 0.2MPa
      pressure for 0h, 5h, or 10h. Flexural strength was obtained by using three-point
      bending test. Micro-mechanical properties (nano-hardness (H) and reduced modulus
      (Er)) were investigated by nanoindentation tests. Scanning electron microscopy
      and X-ray diffraction analyses were performed to identify the micro-structure and
      fracture behavior. The flexure strength, modulus and hardness of zirconia
      increased after 5h aging and decreased after 10h aging. No significant
      alterations of the reduced modulus or hardness of porcelain were detected in the
      whole aging duration. Width of the zirconia-porcelain interface was extended
      towards the bulk of zirconia. The detachment and cracks could be observed in
      zirconia, and the crystal alignment was disorganized in porcelain after 5h aging
      and 10h aging. Mechanical properties of the veneering porcelain are not affected
      by low-temperature aging. However, the expansion and the alterations of micro
      mechanical and micro-structural properties of zirconia-porcelain interface were
      detected.

PMID- 27866057
TI  - Effect of crosslinking in cartilage-like collagen microstructures.
AB  - The mechanical performance of biological tissues is underpinned by a complex and
      finely balanced structure. Central to this is collagen, the most abundant protein
      in our bodies, which plays a dominant role in the functioning of tissues, and
      also in disease. Based on the collagen meshwork of articular cartilage, we have
      developed a bottom-up spring-node model of collagen and examined the effect of
      fibril connectivity, implemented by crosslinking, on mechanical behaviour.
      Although changing individual crosslink stiffness within an order of magnitude had
      no significant effect on modelling predictions, the density of crosslinks in a
      meshwork had a substantial impact on its behaviour. Highly crosslinked meshworks
      maintained a 'normal' configuration under loading, with stronger resistance to
      deformation and improved recovery relative to sparsely crosslinked meshwork.
      Stress on individual fibrils, however, was higher in highly crosslinked
      meshworks. Meshworks with low numbers of crosslinks reconfigured to disease-like
      states upon deformation and recovery. The importance of collagen
      interconnectivity may provide insight into the role of ultrastructure and its
      mechanics in the initiation, and early stages, of diseases such as
      osteoarthritis.

PMID- 27866056
TI  - Towards the mechanical characterization of abdominal wall by inverse analysis.
AB  - The aim of this study is to characterize the passive mechanical behaviour of
      abdominal wall in vivo in an animal model using only external cameras and
      numerical analysis. The main objective lies in defining a methodology that
      provides in vivo information of a specific patient without altering mechanical
      properties. It is demonstrated in the mechanical study of abdomen for hernia
      purposes. Mechanical tests consisted on pneumoperitoneum tests performed on New
      Zealand rabbits, where inner pressure was varied from 0mmHg to 12mmHg. Changes in
      the external abdominal surface were recorded and several points were tracked.
      Based on their coordinates we reconstructed a 3D finite element model of the
      abdominal wall, considering an incompressible hyperelastic material model defined
      by two parameters. The spatial distributions of these parameters (shear modulus
      and non linear parameter) were calculated by inverse analysis, using two
      different types of regularization: Total Variation Diminishing (TVD) and Tikhonov
      (H1). After solving the inverse problem, the distribution of the material
      parameters were obtained along the abdominal surface. Accuracy of the results was
      evaluated for the last level of pressure. Results revealed a higher value of the
      shear modulus in a wide stripe along the craneo-caudal direction, associated with
      the presence of linea alba in conjunction with fascias and rectus abdominis. Non
      linear parameter distribution was smoother and the location of higher values
      varied with the regularization type. Both regularizations proved to yield in an
      accurate predicted displacement field, but H1 obtained a smoother material
      parameter distribution while TVD included some discontinuities. The methodology
      here presented was able to characterize in vivo the passive non linear mechanical
      response of the abdominal wall.

PMID- 27866058
TI  - Timing and duration of nursing from birth affect neonatal porcine uterine matrix
      metalloproteinase 9 and tissue inhibitor of metalloproteinase 1.
AB  - Nursing for 2 d from birth supports neonatal porcine uterine and cervical
      development. However, it is not clear how timing or duration of lactocrine
      signaling from birth (postnatal day = PND 0) affects development of neonatal
      female reproductive tract tissues. Therefore, studies were conducted to determine
      effects of age at first nursing and duration of nursing from birth on specific
      elements of the matrix metalloproteinase (MMP)/tissue inhibitor of
      metalloproteinase (TIMP) system in uterine and cervical tissues at PND 2. When
      nursing was initiated at 0 h or 30 min of age, targeted proteins, including
      proMMP9 and MMP9, were detected in uterine and cervical tissues on PND 2, as was
      uterine TIMP1. However, these proteins were undetectable when nursing was delayed
      for 12 h and when gilts were fed milk replacer for 48 h from birth. Increasing
      the duration of nursing from 30 min to 12 h from birth increased uterine (P <
      0.05) and cervical (P < 0.001) MMP9 levels to those observed in gilts nursed for
      48 h. Similarly, uterine TIMP1 levels increased with duration of nursing. Uterine
      MMP2 levels were detectable but unaffected by age at first nursing or duration of
      nursing from birth. Uterine MMP2 and MMP9 activities, monitored by zymography,
      reflected immunoblotting data. Results provide evidence for the utility of MMP9
      and TIMP1 as markers of age- and lactocrine-sensitive porcine female reproductive
      tract development.

PMID- 27866059
TI  - Glucocorticoid metabolism in equine follicles and oocytes.
AB  - The objective of this study was to determine whether (1) systemic and
      intrafollicular cortisol concentrations in horses are directly related and (2)
      supraphysiological levels of glucocorticoids affect in vitro maturation (IVM)
      rates of oocytes. Specifically, we studied the (1) changes in the intrafollicular
      cortisol and progesterone in context with granulosa cell gene expression during
      maturation of equine follicles (from 5-9 mm, 10-14 mm, 15-19 mm, 20-24 mm, and
      >=25 mm in diameter) and (2) effects of cortisol supplementation on IVM rates and
      gene expression of equine cumulus-oocyte complexes (COCs). For these purposes,
      follicular fluid, granulosa cells, and COCs were collected from 12 mares (mean
      age 8.6 +/- 0.5 yr) by transvaginal aspiration. Cortisol and progesterone
      concentrations in follicular fluid from follicles >=25 mm were greater (P < 0.05)
      than in all other follicle classes and were positively correlated (r = 0.8; P <
      0.001). Plasma concentrations of cortisol and progesterone did not differ before
      and after follicle aspiration (P > 0.05). In granulosa cells, gene expression of
      NR3C1, HSD11B1, HSD11B2, and CYP21A2 did not differ (P > 0.05) among different
      follicle classes. Maturation rates were similar (P > 0.05) among groups,
      regardless of the cortisol concentration in the IVM medium. In cumulus cells,
      messenger RNA expression of genes involved in glucocorticoid mechanism and
      apoptosis was either increased (NR3C1 and BCL2) or decreased (HSD11B2) by
      treatment (P < 0.01). In oocytes, gene expression of maturation markers (BMP15
      and GDF9) was affected (P < 0.001) by cortisol treatment. This study demonstrates
      the involvement of glucocorticoids in follicle and oocyte maturation and cortisol
      modulation by HSD11B2 in equine COCs. Our data provide further information for
      understanding the normal ovarian endocrine physiology which might in turn also
      help improve equine assisted reproduction techniques.

PMID- 27866060
TI  - Psychometric properties of the Spanish version of the Cannabis Use Problems
      Identification Test among Chilean university students: A validation study.
AB  - BACKGROUND: In Chile, concerns mount about escalating cannabis use. Thus, it is
      important to have tools for early identification of at-risk users. The Cannabis
      Use Problems Identification Test (CUPIT) is a useful screening tool, and the aim
      of this study was to examine the psychometric properties of its Spanish version
      among Chilean university students. METHODS: The CUPIT was translated into
      Spanish, pre-tested in a focus group (n=8), and then tested through an online
      survey (n=3798, 28% response rate). Of the 1061 respondents, 578 reported 12
      month cannabis use. Internal reliability, internal structure, and concurrent
      validity (using the Cannabis Abuse Screening Test [CAST]) were obtained. Test
      retest reliability was calculated (n=150) at 3-4 weeks (30% of attrition rate).
      Discriminative validity was evaluated comparing CUPIT subscales and four DSM-IV
      diagnostic groups. Receiving operator characteristic (ROC) curve analysis
      assessed sensitivity and specificity. RESULTS: Test-retest Pearson correlation
      between total CUPIT scores of 0.90 (p<0.001), and highly significant Kendall Tau
      b coefficients for individual items (p<0.001) indicated excellent reliability.
      Concordance between the CUPIT and CAST (Pearson correlation 0.73, p<0.001)
      indicated good concurrent validity. ANOVA revealed significant differences in
      CUPIT scores between the four DSM-IV diagnostic groups (p<0.001), indicative of
      good discriminative validity. ROC analysis (gold standard: DSM-IV
      abuse/dependence) yielded an AUC value of 0.72, indicating acceptable
      discriminative capability. CONCLUSIONS: The Spanish CUPIT is reliable, valid, and
      accepted by the university population studied, and, thus, a potentially useful
      tool for identifying both problematic and at-risk users.

PMID- 27866061
TI  - Patterns of drugs & poisons in southern area of South Korea in 2014.
AB  - The southern area of South Korea consists of three parts; Busan, Ulsan and
      Gyeongsangnam-do. Busan Institute of National Forensic Service (NFS) performed
      about 50,000 cases throughout the southern area in 2014, occupying over 15% of
      total cases covered by NFS. In this study, patterns of drugs and poisons in the
      southern area of South Korea were investigated. The investigation was carried out
      by the laboratory information management system of NFS between January and
      December of 2014. As results, a total of 606 autopsy cases were performed by
      Busan Institute of NFS in 2014. Among them, 15 cases were determined as drug
      intoxication or poisons as the cause of death, taking up 2.5% of total cases: 5
      cases of intoxication by drugs, 5 by agricultural pesticides, 3 by illicit drugs,
      and 1 each by detergents and chemical substances. A total of 108 drugs in
      postmortem bloods were detected from the autopsy cases, and the top 5 drugs were
      chlorpheniramine, tramadol, diazepam, zolpidem and lidocaine. Meanwhile, a total
      of 1,728 cases were submitted for illicit drug testing in 2014. Among them, hair
      was the most common type of specimens, and the rate of positive detection of
      methamphetamine from the hair, urine, and seized materials in the southern area
      was over 50% in all cases, indicating that this is the most commonly abused drug
      in South Korea. A total of 12 types of novel psychoactive substances (NPSs) were
      detected in the southern area in 2014; 10 were identified as synthetic
      cannabinoids and 2 as alkyl nitrites.

PMID- 27866062
TI  - Gunshot residue contamination of the hands of police officers following start-of
      shift handling of their firearm.
AB  - If police officers are contaminated with gunshot residue (GSR) through the normal
      receiving, checking, loading, and securing of their issued firearm, there is the
      potential for secondary transfer of GSR to anyone those officers arrest during
      their shift. This 3-part study examined the level of GSR contamination of police
      officers following the start-of-shift handling of their standard issue firearm,
      the impact that hand-washing or the use of a self-drying hand-wash had on the
      level of GSR contamination, and the likelihood of officers re-contaminating their
      hands through contact with the exposed hand-grip of their holstered hand-gun.
      Almost 85% (28/33) of officers sampled had 3-component GSR particles on their
      hands immediately following the start-of-shift handling of their firearm. There
      was an average of 64 such particles over the 33 officers sampled. Of the 17
      officers who washed their hands after securing their firearm, a single 3
      component particle was recovered from the hands of one officer. GSR particles
      (maximum of 4) were recovered from 3 of the 14 officers who used self-drying hand
      gel following firearm handling. 3-component particles (maximum of 7) were
      recovered from the hand-grips of 12 of the 34 unissued handguns sampled.

PMID- 27866063
TI  - Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond.
AB  - Cardiotoxicity induced by chemotherapeutic agents and radiotherapy is a growing
      problem. In recent years, an increasing number of new drugs with targeted action
      have been designed. These molecules, such as monoclonal antibodies and tyrosine
      kinase inhibitors, can cause different type of toxicities compared to traditional
      chemotherapy. However, they can also cause cardiac complications such as heart
      failure, arterial hypertension, QT interval prolongation and arrhythmias.
      Currently, a field of intense research is the vascular toxicity induced by new
      biologic drugs, particularly those which inhibit vascular endothelial growth
      factor (VEGF) and its receptor (VEGF-R) and other tyrosine kinases. In this
      review, we aim at focusing on the problem of vascular toxicity induced by new
      targeted therapies, chemotherapy and radiotherapy, and describe the main
      mechanisms and emphasizing the importance of early diagnosis of vascular damage,
      in order to prevent clinical complications.

PMID- 27866064
TI  - Incretin-based therapy for type 2 diabetes: A real class effect?

PMID- 27866065
TI  - The effect of vitamin D supplementation on hypertension in non-CKD populations: A
      systemic review and meta-analysis.
AB  - OBJECTIVES: To investigate the vitamin D supplementation on blood pressure
      control by a systemic review and meta-analysis. METHODS: Randomized controlled
      clinical trials were analyzed, which date from eight studies in databases
      including MEDLINE, EMBASE, Clinical trials, China Integrated Knowledge Resources
      Database and the Cochrane library. RESULTS: Total 917 patients from eight
      randomized controlled trials (RCTs), treatment with vitamin D for more than
      3months were analyzed. Meta-analysis showed that vitamin D supplementation
      slightly reduced the systolic blood pressure (SBP) by 1.964mmHg (95% CI, 0.362
      3.566; P=0.016), but not lowered diastolic blood pressure (SMD: -0.087, 95% CI, 
      0.208-0.033; P=0.155). Subgroup analysis also showed that sBP lowering by vitamin
      D supplementation was not dose-dependent. Comparison to placebo, there is also no
      statistical difference in SBP lowering by vitamin D supplementation. CONCLUSIONS:
      This meta-analysis indicated that vitamin D is not an antihypertensive agent
      although it has a moderate SBP lowering effect. More RCTs are required to observe
      the role of vitamin D plus other antihypertensive drugs in blood pressure
      control, and define the optimum dose, dosing interval, and type of vitamin D to
      administer.

PMID- 27866068
TI  - An abnormal ocular motor manifestation of Joubert syndrome.
AB  - Joubert syndrome is a congenital neurodevelopmental disorder primarily affecting
      the midbrain and hindbrain. It is characterized by ataxia, hypotonia, and
      developmental delay as well as apnea or abnormal ocular motor function. We
      describe and present a video of a child with Joubert syndrome with an alternating
      skew deviation in primary position rather than on lateral gaze, which is a more
      characteristic phenotype of this condition.

PMID- 27866067
TI  - Escalating and de-escalating treatment in HER2-positive early breast cancer.
AB  - The current standard adjuvant systemic treatment of early HER2-positive breast
      cancer consists of chemotherapy plus 12months of trastuzumab, with or without
      endocrine therapy. Several trials have investigated modifications of the standard
      treatment that are shorter and less resource-demanding (de-escalation) or
      regimens that aim at dual HER2 inhibition or include longer than 12months of HER2
      targeted treatment (escalation). Seven randomized trials investigate shorter than
      12months of trastuzumab treatment duration. The shorter durations were not
      statistically inferior to the 1-year duration in the 3 trials with survival
      results available, but 2 of the trials were small and 1 had a relatively short
      follow-up time of the patients at the time of reporting. The pathological
      complete response (pCR) rates were numerically higher in all 9 randomized trials
      that compared chemotherapy plus dual HER2 inhibition consisting of trastuzumab
      plus either lapatinib, neratinib, or pertuzumab with chemotherapy plus
      trastuzumab as neoadjuvant treatments, but the superiority of chemotherapy plus
      dual HER2-inhibition over chemotherapy plus trastuzumab remains to be
      demonstrated in the adjuvant setting. One year of adjuvant trastuzumab was as
      effective as 2years of trastuzumab in the HERA trial, and was associated with
      fewer side-effects. Extending 1-year adjuvant trastuzumab treatment with 1year of
      neratinib improved disease-free survival in the ExteNET trial, but the patient
      follow-up times are still short, and no overall survival benefit was reported.
      Several important trials are expected to report results in the near future and
      may modify the current standard.

PMID- 27866066
TI  - Terminate lung cancer (TLC) study-A mixed-methods population approach to increase
      lung cancer screening awareness and low-dose computed tomography in Eastern
      Kentucky.
AB  - For low dose CT lung cancer screening to be effective in curbing disease
      mortality, efforts are needed to overcome barriers to awareness and facilitate
      uptake of the current evidence-based screening guidelines. A sequential mixed
      methods approach was employed to design a screening campaign utilizing messages
      developed from community focus groups, followed by implementation of the outreach
      campaign intervention in two high-risk Kentucky regions. This study reports on
      rates of awareness and screening in intervention regions, as compared to a
      control region.

PMID- 27866069
TI  - A case of recurrent, grade 3 corneal choriostoma after surgical excision.
AB  - We report a case of congenital grade 3 corneal choriostoma accompanied by
      anterior staphyloma. The tumor was excised by deep lamellar dissection, and the
      defect was filled with multilayer amniotic membranes. On histologic examination,
      the excised tumor contained demislike connective tissues, dermal adnexa (hair
      follicles and sebaceous gland), and adipose tissue, and was lined by keratinizing
      squamous epithelium. One month after surgery, the tumor recurred and
      progressively enlarged.

PMID- 27866070
TI  - Spontaneous rupture of chorioretinal coloboma in an 8-year-old child is treated
      by temporal fascia graft.
AB  - We report the rare case of an 8-year-old boy with spontaneous scleral perforation
      secondary to an isolated congenital chorioretinal coloboma. Visual acuity was
      20/200 and examination revealed severe hypotony with subcapsular cataract,
      complete exudative retinal detachment, hypotonous optic nerve swelling, and
      hypotony retinal fold. In the temporal periphery, there was a chorioretinal
      coloboma with a central full-thickness defect. The scleral defect was
      successfully treated with an autologous temporalis fascia graft. One year later,
      and after cataract surgery, visual acuity had improved to 20/20, with normal
      intraocular pressure.

PMID- 27866071
TI  - The CD4/CD8 ratio is associated with coronary artery disease (CAD) in elderly
      Chinese patients.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      number of circulating T cells and coronary artery disease (CAD) in an elderly
      Chinese population. METHODS: A total of 295 elderly inpatients (age>=60) were
      included in this cross-sectional study. Their clinical and biochemical
      characteristics were recorded. Patients were divided to two groups: control
      patients and CAD patients. The risk factors of CAD were explored by binary
      logistic regression analysis. RESULTS: Compared with control patients, the ratio
      of CD4 to CD8 T cells was significantly increased in CAD patients. There was no
      difference in the number of CD3, CD4, and CD8 T cells between the two groups.
      Multiple logistic regression analysis showed that CAD was independently
      associated with age, gender, body mass index (BMI), systolic blood pressure
      (SBP), chronic heart failure (CHF) and the CD4/CD8 ratio. In addition, after
      adjusting for different clinical parameters (including gender, age, CHF,
      hypertension, arrhythmia, SBP, and BMI), the risk of CAD was significantly
      increased in patients with a CD4/CD8 ratio>1.5. CONCLUSIONS: There was a strong
      and independent association between the ratio of CD4/CD8 and CAD in elderly
      Chinese population.

PMID- 27866072
TI  - General expressions for R1rho relaxation for N-site chemical exchange and the
      special case of linear chains.
AB  - Exploration of dynamic processes in proteins and nucleic acids by spin-locking
      NMR experiments has been facilitated by the development of theoretical
      expressions for the R1rho relaxation rate constant covering a variety of kinetic
      situations. Herein, we present a generalized approximation to the chemical
      exchange, Rex, component of R1rho for arbitrary kinetic schemes, assuming the
      presence of a dominant major site population, derived from the negative
      reciprocal trace of the inverse Bloch-McConnell evolution matrix. This
      approximation is equivalent to first-order truncation of the characteristic
      polynomial derived from the Bloch-McConnell evolution matrix. For three- and four
      site chemical exchange, the first-order approximations are sufficient to
      distinguish different kinetic schemes. We also introduce an approach to calculate
      R1rho for linear N-site schemes, using the matrix determinant lemma to reduce the
      corresponding 3N*3N Bloch-McConnell evolution matrix to a 3*3 matrix. The first-
      and second order-expansions of the determinant of this 3*3 matrix are closely
      related to previously derived equations for two-site exchange. The second-order
      approximations for linear N-site schemes can be used to obtain more accurate
      approximations for non-linear N-site schemes, such as triangular three-site or
      star four-site topologies. The expressions presented herein provide powerful
      means for the estimation of Rex contributions for both low (CEST-limit) and high
      (R1rho-limit) radiofrequency field strengths, provided that the population of one
      state is dominant. The general nature of the new expressions allows for
      consideration of complex kinetic situations in the analysis of NMR spin
      relaxation data.

PMID- 27866073
TI  - Drivers' detection of roadside targets when driving vehicles with three headlight
      systems during high beam activation.
AB  - A previous open-road experiment indicated that curve-adaptive HID headlights
      driven with low beams improved drivers' detection of low conspicuity targets
      compared with fixed halogen and fixed HID low beam systems. The current study
      used the same test environment and targets to assess whether drivers' detection
      of targets was affected by the same three headlight systems when using high
      beams. Twenty drivers search and responded for 60 8*12inch targets of high or low
      reflectance that were distributed evenly across straight and curved road sections
      as they drove at 30 mph on an unlit two-lane rural road. The results indicate
      that target detection performance was generally similar across the three systems.
      However, one interaction indicated that drivers saw low reflectance targets on
      straight road sections from further away when driving with the fixed halogen high
      beam condition compared with curve-adaptive HID high beam headlights and also
      indicated a possible benefit for the curve-adaptive HID high beams for high
      reflectance targets placed on the inside of curves. The results of this study
      conflict with the previous study of low beams, which showed a consistent benefit
      for the curve-adaptive HID low beams for targets placed on curves compared with
      fixed HID and fixed halogen low beam conditions. However, a comparison of mean
      detection distances from the two studies indicated uniformly longer mean target
      detection distances for participants driving with high beams and implicates the
      potential visibility benefits for systems that optimize proper high beam use.

PMID- 27866074
TI  - Environmentally induced tissue responses of hematopoietic system in abu mullet
      (Liza abu) and tiger tooth croaker (Otolithes ruber) from the Persian Gulf.
AB  - The present investigation aimed to assess the possibility of using plasma levels
      of erythropoietin (EPO) hormone and tissue changes of hematopoietic organs as
      biomarkers of environmental pollution in abu mullet (Liza abu) and tiger tooth
      croaker (Otolithes ruber) collected from Musa Creek (northwest of the Persian
      Gulf). 120 L. abu and O. ruber were collected from five stations at the Musa
      Creek: Petrochemical, Ghanam, Doragh, Zangi and Patil stations. Blood samples
      were obtained from the caudal vein. Tissue samples were also taken from the
      spleen and head kidney, and tissue sections were prepared according to routine
      histological methods. The concentrations of Hg, Pb, Zn, Cu, and Cd were also
      measured in the sediment samples. The minimum level of EPO and the most severe
      tissue changes were determined in fish collected near a Petrochemical station.
      This station is adjacent to the Imam Khomeini Petrochemical Complex and receives
      highly contaminated effluents from this complex. The highest degree of
      contamination (Cd) also belonged to this station. The fish collected from the
      Patil station represented the highest EPO level and the least tissue changes.
      This station exhibited a lesser degree of contamination. Based on the results,
      there was a significant correlation between the plasma level of EPO hormone and
      the degree of environmental contamination.

PMID- 27866075
TI  - Bioaccumulation and subcellular partitioning of Cr(III) and Cr(VI) in the
      freshwater green alga Chlamydomonas reinhardtii.
AB  - Chromium occurs in aquatic environments under two main redox forms, namely
      Cr(III) and Cr(VI), with different geochemical and biochemical properties. Cr(VI)
      readily crosses biological membranes of living organisms and once inside the
      cells it undergoes a rapid reduction to Cr(III). The route of entry for the
      latter form is, however, poorly known. Using the radioactive tracer 51Cr we
      compared the accumulation (absorption and adsorption) of the two Cr forms by the
      green unicellular alga Chlamydomonas reinhardii after 1h and 72h of exposure to
      100nM of either Cr(III) or Cr(VI) at pH 7. Both Cr forms had similar
      accumulation, with a major part in the extracellular (adsorbed) fraction after 1h
      and a major part of total accumulated Cr in the intracellular (absorbed) fraction
      after 72h. We also investigated the intracellular partitioning of Cr using an
      operational fractionation scheme and found that both Cr forms had similar
      distributions among fractions: Cr was mostly associated with organelles (23+/-12%
      after 1h and 37+/-7% after 72h) and cytosolic heat-stable proteins and peptides
      (39+/-18% after 1h and 35+/-3% after 72h) fractions. Further investigations using
      a metallomic approach (SEC-ICP-MS) were performed with the heat-stable proteins
      and peptides fraction to compare the distribution of the two Cr forms among
      various biomolecules of this fraction. One Cr-binding biomolecule (~28kDa)
      appeared after 1h of exposure for both Cr species. After 72h another biomolecule
      of lower molecular weight (~0.7kDa) was involved in binding Cr and higher signal
      intensities were observed for Cr(VI) than for Cr(III). We show, for the first
      time, that both Cr(III) and Cr(VI) have similar fate within algal cells,
      supporting the tenet that a unique redox form occurs within cells.

PMID- 27866076
TI  - Antioxidant properties of tea blunt ROS-dependent lipogenesis: beneficial effect
      on hepatic steatosis in a high fat-high sucrose diet NAFLD obese rat model.
AB  - Oxidative stress could trigger lipid accumulation in liver and thus hepatic
      steatosis. Tea is able to prevent liver disorders, but a direct link between
      antioxidant capacities and prevention of steatosis has not been reported yet. We
      aimed to investigate such relationship in a rat model of high fat-high sucrose
      diet (HFS)-induced obesity and to explore more deeply the mechanisms in isolated
      hepatocytes. Wistar rats were divided into a control group (standard diet), an
      HFS group (high fat-sucrose diet) and an HFS+tea group (HFS diet with ad-libitum
      access to tea drink). Body weight, fat mass, glycemic parameters in blood, lipid
      and oxidative stress parameters in blood and liver were measured in each group
      after 14 weeks. Isolated hepatocytes were treated with the reactive oxygen
      species (ROS) inducer t-BHP in the presence or not of antioxidants (tempol or
      tea), and superoxide anion production and lipid accumulation were measured using
      specific fluorescent probes. We reported that the HFS diet highly increased
      hepatic lipids content, while tea consumption attenuated steatosis and improved
      the oxidative status (decrease in hepatic oxidative stress, increase in plasma
      total antioxidant capacity). The role of antioxidant properties of tea in such
      phenomenon was confirmed in primary cultured rat hepatocytes. Indeed, the
      increase of mitochondrial ROS production with t-BHP resulted in lipid
      accumulation in hepatocytes (positive linear regression), and antioxidants
      (tempol or tea) normalized both. We reported that the antioxidant properties of
      tea protect rats from an obesogenic HFS diet-induced hepatic steatosis by
      counteracting the ROS-dependent lipogenesis.

PMID- 27866077
TI  - The concept of double inlet-double outlet right ventricle: a distinct congenital
      heart disease.
AB  - The aim of this study was to estimate the incidence and to analyze the anatomy of
      double inlet-double outlet right ventricle complex and its associated cardiac
      anomalies in our autopsy series. Among the 1640 hearts with congenital heart
      disease of our Anatomical Collection, we reviewed the specimens with double inlet
      double outlet right ventricle, according to the sequential-segmental analysis,
      identifying associated cardiac anomalies and examining lung histology to assess
      the presence of pulmonary vascular disease. We identified 14 hearts with double
      inlet-double outlet right ventricle (0.85%). Right atrial isomerism was observed
      in 10 hearts, situs solitus in 3 and left atrial isomerism in one. Regarding the
      mode of atrioventricular connection, all hearts but one had a common
      atrioventricular valve. Systemic or pulmonary venous abnormalities were noted in
      all patients with atrial isomerism. In nine patients a valvular or subvalvular
      pulmonary stenosis was present. Among the functionally "univentricular hearts",
      double inlet- double outlet right ventricle represents a peculiar entity, mostly
      in association with right atrial isomerism. Multiple cardiac anomalies are
      associated and may complicate surgical repair.

PMID- 27866078
TI  - A pH Indicator-linked Immunosorbent assay following direct amplification strategy
      for colorimetric detection of protein biomarkers.
AB  - A new pH indicator-linked immunosorbent assay (PILISA) reached pg/mL sensitivity
      based on pH indicator molecules loaded carbon nitride nanosheets as signal
      enhancer has been developed for colorimetric detection of protein biomarkers. As
      the secondary antibody binds to the carbon nitride nanosheets, the carbon nitride
      nanosheets and pH indicator complex as the signal amplification platform for
      colour change by detecting absorbance of pH indicator. The colour change was
      resulted from the releasing of pH indicator molecules from carbon nitride
      nanosheets triggered by alkali solution (AS). In this novel PILISA, the intensity
      absorbance of pH indicator is proportional to the concentration of the disease
      marker. The outstanding detection performance of the PILISA can be attributed to
      the following reasons: (1) ultrathin carbon nitride nanosheets with a larger
      surface area could adsorb abundant phenolphthalein (PP) molecules through
      hydrophobic interactions as well as the resulted PP anions can be free easily
      released into aqueous solution, leading to an obvious allochroic response; (2)
      the signal intensity is precisely determined by the amount of PP molecules
      loading onto the carbon nitride nanosheets surface, which ensures simple, low
      cost and stable colorimetric detection. As expected, this new PILISA method
      offered an enzyme-free approach followed enzyme-linked immunosorbent assay
      format, which showed great promising potential as an innovative robust assay
      method for practical clinical applications.

PMID- 27866079
TI  - Multimodal plasmonic biosensing nanostructures prepared by DNA-directed
      immobilization of multifunctional DNA-gold nanoparticles.
AB  - Biofunctional multimodal plasmonic nanostructures suitable for multiplexed
      localized surface plasmon resonance (LSPR) biosensing have been created by DNA
      directed immobilization (DDI) of two distinct multifunctional biohybrid gold
      nanoparticles. Gold nanoparticles (AuNP) of distinct sizes, and therefore showing
      distinct plasmon resonant peaks (RP), have been biofunctionalized and codified
      with two different single stranded-DNA (ssDNA) chains. One of these
      oligonucleotide chains has been specifically designed to direct each AuNP to a
      distinct location of the surface of a DNA microarray chip through specific
      hybridization with complementary oligonucleotide strands. Scanning Electron
      Microscopy (SEM) has been used to demonstrate selective immobilization of each
      AuNP on distinct spots. The second ssDNA chain of the AuNPs provides the
      possibility to introduce by hybridization distinct types of bioactive molecules
      or bioreceptors, on a reversible manner. In this work, hapten-oligonucleotide
      bioconjugate probes, with sequences complementary to the second ssDNA linked to
      the AuNP, have been synthesized and used to create multiplexed hapten
      biofuncionalized plasmonic nanostructures. The oligonucleotide probes consist on
      anabolic androgenic steroid haptens (AAS) covalently linked to specifically
      designed oligonucleotide sequences. The biofunctionality of these plasmonic
      nanostructures has been demonstrated by fluorescent microarray immunoassay and
      LSPR measurements, recording the shift of the RP produced after the antibody
      binding to the corresponding hapten-oligonucleotide probes immobilized on the
      nanostructured surface. Preliminary data show that this approach could allow
      manufacturing multifunctional multimodal LSPR chips for multiplexed analysis of
      different substances reaching very good detectability. Thus, small molecular
      weigh, analytes such as stanozolol (ST,) could be detected at concentrations in
      the low nM range. The results here presented open the door for an easy way to
      construct site-encoded multiplexed multimodal LSPR sensor transducers, combining
      the DDI strategies with multimodal biohybrid nanoparticles showing distinct
      optical properties.

PMID- 27866080
TI  - Highly sensitive detection of cancer cells with an electrochemical cytosensor
      based on boronic acid functional polythiophene.
AB  - The detection of cancer cells through important molecular recognition target such
      as sialic acid is significant for the clinical diagnosis and treatment. There are
      many electrochemical cytosensors developed for cancer cells detection but most of
      them have complicated fabrication processes which results in poor reproducibility
      and reliability. In this study, a simple, low-cost, and highly sensitive
      electrochemical cytosensor was designed based on boronic acid-functionalized
      polythiophene. In cytosensors fabrication simple single-step procedure was used
      which includes coating pencil graphite electrode (PGE) by means of electro
      polymerization of 3-Thienyl boronic acid and Thiophen. Electrochemical impedance
      spectroscopy and cyclic voltammetry were used as an analytical methods to
      optimize and measure analytical performances of PGE/P(TBA0.5Th0.5) based
      electrode. Cytosensor showed extremely good analytical performances in detection
      of cancer cells with linear rage of 1*101 to 1*106 cellsmL-1 exhibiting low
      detection limit of 10 cellsmL-1 and incubation time of 10min. Next to excellent
      analytical performances, it showed high selectivity towards AGS cancer cells when
      compared to HEK 293 normal cells and bone marrow mesenchymal stem cells (BM
      hMSCs). This method is promising for future applications in early stage cancer
      diagnosis.

PMID- 27866081
TI  - Delineating baseflow contribution areas for streams - A model and methods
      comparison.
AB  - This study addresses the delineation of areas that contribute baseflow to a
      stream reach, also known as stream capture zones. Such areas can be delineated
      using standard well capture zone delineation methods, with three important
      differences: (1) natural gradients are smaller compared to those produced by
      supply wells and are therefore subject to greater numerical errors, (2) stream
      discharge varies seasonally, and (3) stream discharge varies spatially. This
      study focuses on model-related uncertainties due to model characteristics,
      discretization schemes, delineation methods, and particle tracking algorithms.
      The methodology is applied to the Alder Creek watershed in southwestern Ontario.
      Four different model codes are compared: HydroGeoSphere, WATFLOW, MODFLOW, and
      FEFLOW. In addition, two delineation methods are compared: reverse particle
      tracking and reverse transport, where the latter considers local-scale parameter
      uncertainty by using a macrodispersion term to produce a capture probability
      plume. The results from this study indicate that different models can calibrate
      acceptably well to the same data and produce very similar distributions of
      hydraulic head, but can produce different capture zones. The stream capture zone
      is found to be highly sensitive to the particle tracking algorithm. It was also
      found that particle tracking by itself, if applied to complex systems such as the
      Alder Creek watershed, would require considerable subjective judgement in the
      delineation of stream capture zones. Reverse transport is an alternative and more
      reliable approach that provides probability intervals for the baseflow
      contribution areas, taking uncertainty into account. The two approaches can be
      used together to enhance the confidence in the final outcome.

PMID- 27866083
TI  - Neuroanatomical differences in FAST and SLOW rat strains with differential
      vulnerability to kindling and behavioral comorbidities.
AB  - OBJECTIVE: The neurobiological factors underlying a predisposition towards
      developing epilepsy and its common behavioral comorbidities are poorly
      understood. FAST rats are a strain that has been selectively bred for enhanced
      vulnerability to kindling, while the SLOW strain has been bred to be resistant to
      kindling. FAST rats also exhibit behavioral traits reminiscent of those observed
      in neurodevelopmental disorders (autism spectrum disorder (ASD)/attention
      deficit/hyperactivity disorder (ADHD)) commonly comorbid with epilepsy. In this
      study, we aimed to investigate neuroanatomical differences between these strains
      that may be associated with a differential vulnerability towards these
      interrelated disorders. METHODS: Ex vivo high-resolution magnetic resonance
      imaging on adult male FAST and SLOW rat brains was performed to identify
      morphological differences in regions of interest between the two strains.
      Behavioral examination using open-field, water consumption, and restraint tests
      was also conducted on a subgroup of these rats to document their differential
      ASD/ADHD-like behavior phenotype. Using optical stereological methods, the volume
      of cerebellar granule, white matter, and molecular layer and number of Purkinje
      cells were compared in a separate cohort of adult FAST and SLOW rats. RESULTS:
      Behavioral testing demonstrated hyperactivity, impulsivity, and polydipsia in
      FAST versus SLOW rats, consistent with an ASD/ADHD-like phenotype. Magnetic
      resonance imaging analysis identified brain structural differences in FAST
      compared with SLOW rats, including increased volume of the cerebrum, corpus
      callosum, third ventricle, and posterior inferior cerebellum, while decreased
      volume of the anterior cerebellar vermis. Stereological measurements on
      histological slices indicated significantly larger white matter layer volume,
      reduced number of Purkinje cells, and smaller molecular layer volume in the
      cerebellum in FAST versus SLOW rats. SIGNIFICANCE: These findings provide
      evidence of structural differences between the brains of FAST and SLOW rats that
      may be mechanistically related to their differential vulnerability to kindling
      and associated comorbid ASD/ADHD-like behaviors.

PMID- 27866084
TI  - Engineering cell signaling modulators from native protein-protein interactions.
AB  - Recent studies on genome sequencing and genetic screens with RNAi and CRISPR
      technology have revolutionized our understanding of aberrant signaling networks
      in human diseases. A strategy combining both genetic and protein-based
      technologies should be at the heart of modern drug-development efforts,
      particularly in the era of precision medicine. Thus, there is an urgent need for
      efficient platforms to develop probes that can modulate protein function in cells
      to validate drug targets and to develop therapeutic leads. Advanced protein
      engineering has enabled the rapid production of monoclonal antibodies and small
      protein scaffold affinity reagents for diverse protein targets. Here, we review
      the most recent progress on engineering natural protein-protein interactions for
      modulation of cell signaling.

PMID- 27866082
TI  - Auditory verbal hallucinations and continuum models of psychosis: A systematic
      review of the healthy voice-hearer literature.
AB  - Recent decades have seen a surge of research interest in the phenomenon of
      healthy individuals who experience auditory verbal hallucinations, yet do not
      exhibit distress or need for care. The aims of the present systematic review are
      to provide a comprehensive overview of this research and examine how healthy
      voice-hearers may best be conceptualised in relation to the diagnostic versus
      'quasi-' and 'fully-dimensional' continuum models of psychosis. A systematic
      literature search was conducted, resulting in a total of 398 article titles and
      abstracts that were scrutinised for appropriateness to the present objective.
      Seventy articles were identified for full-text analysis, of which 36 met criteria
      for inclusion. Subjective perceptual experience of voices, such as loudness or
      location (i.e., inside/outside head), is similar in clinical and non-clinical
      groups, although clinical voice-hearers have more frequent voices, more negative
      voice content, and an older age of onset. Groups differ significantly in beliefs
      about voices, control over voices, voice-related distress, and affective
      difficulties. Cognitive biases, reduced global functioning, and psychiatric
      symptoms such as delusions, appear more prevalent in healthy voice-hearers than
      in healthy controls, yet less than in clinical samples. Transition to mental
      health difficulties is increased in HVHs, yet only occurs in a minority and is
      predicted by previous mood problems and voice distress. Whilst healthy voice
      hearers show similar brain activity during hallucinatory experiences to clinical
      voice-hearers, other neuroimaging measures, such as mismatch negativity, have
      been inconclusive. Risk factors such as familial and childhood trauma appear
      similar between clinical and non-clinical voice-hearers. Overall the results of
      the present systematic review support a continuum view rather than a diagnostic
      model, but cannot distinguish between 'quasi' and 'fully' dimensional models.
      Healthy voice-hearers may be a key resource in informing transdiagnostic
      approaches to research of auditory hallucinations.

PMID- 27866085
TI  - Cognitive bias modification of interpretation in children with social anxiety
      disorder.
AB  - Negative (or a lack of positive) interpretation of ambiguous social situations
      has been hypothesised to maintain social anxiety disorder in children, yet there
      is currently limited evidence to support this. Cognitive Bias Modification of
      Interpretation (CBM-I) provides a means to explore the causal influence of
      interpretation bias on social anxiety disorder, and has been associated with a
      reduction in social anxiety symptoms in adults. Seven to twelve year old children
      with a diagnosis of social anxiety disorder completed CBM-I training, adapted
      from materials designed for socially anxious children in the community, or no
      training. Effects on interpretation bias and social anxiety were assessed. The
      adapted CBM-I training was not associated with significant changes in benign or
      negative interpretation. Unsurprisingly given the lack of successful
      interpretation training, there were no significant changes in child or parent
      reported social anxiety symptoms, clinician-rated severity or diagnoses and
      change in interpretation was not significantly associated with change in social
      anxiety. These findings contrast with some studies with community populations
      although it is possible that more intensive CBM-I training is required to fully
      test this hypothesis among clinical groups.

PMID- 27866086
TI  - The role of postural instability/gait difficulty and fear of falling in
      predicting falls in non-demented older adults.
AB  - INTRODUCTION: Postural instability/gait difficulty (PIGD) and fear of falling
      (FoF) frequently co-exist, but their individual predictive values for falls have
      not been compared in aging. This study aims to determine both independent and
      combined effect of PIGD and FoF to falls in older adults without dementia.
      METHODS: PIGD and other extrapyramidal signs were systematically assessed in 449
      community-dwelling participants without Parkinson's disease (76.48+/-6.61 ys;
      56.8% female) enrolled in this longitudinal cohort study. Presence of FoF was
      measured by a single-item question (Do you have a FoF?) and self-confidence by
      the Activities-specific Balance Confidence scale (ABC scale). RESULTS: One
      hundred sixty-nine participants (38%) had an incident fall over a mean follow-up
      of 20.1+/-12.2months. PIGD was present in 32% and FoF in 23% of the participants.
      Both PIGD (adjusted hazard ratio (aHR): 2.28; p=0.016) and self-confidence (aHR:
      0.99; p=0.040) predicted falls when entered simultaneously in the Cox model.
      However, presence of FoF (aHR: 1.99; p=0.021) and self-confidence (aHR: 0.98;
      p=0.006) predicted falls only in individuals with PIGD. CONCLUSIONS: PIGD and FoF
      were associated with future falls in older adults without dementia but FoF was a
      fall's predictor only in individuals with PIGD.

PMID- 27866088
TI  - Is ketogenic diet treatment hepatotoxic for children with intractable epilepsy?
AB  - PURPOSE: Long-term ketogenic diet (KD) treatment has been shown to induce liver
      steatosis and gallstone formation in some in vivo and clinical studies. The aim
      of this retrospective study was to evaluate the hepatic side effects of KD in
      epileptic children. METHOD: A total of 141 patients (mean age: 7.1+/-4.1years [2
      18 years], 45.4% girls), receiving KD at least one year for intractable epilepsy
      due to different diagnoses (congenital brain defects, GLUT-1 deficiency, West
      syndrome, tuberous sclerosis, hypoxic brain injury, etc.) were included in the
      study. Serum triglyceride, cholesterol, aminotransferase, bilirubin, protein and
      albumin levels and abdominal ultrasonography were recorded before and at 1, 3, 6,
      and 12 months following after diet initiation. RESULTS: The mean duration of KD
      was 15.9+/-4.3months. At one month of therapy, three patients had elevated
      alanine and aspartate aminotransferase levels. These patients were receiving
      ketogenic diet for Doose syndrome, idiopathic epilepsy and GLUT-1 deficiency.
      Hepatosteatosis was detected in three patients at 6 months of treatment. Two of
      these patients were treated with KD for the primary diagnosis of tuberous
      sclerosis and one for Landau Kleffner syndrome. Cholelithiasis was detected in
      two patients at 12 months of treatment. They were receiving treatment for West
      syndrome and hypoxic brain injury sequelae. CONCLUSION: Long-term ketogenic diet
      treatment stimulates liver parenchymal injury, hepatic steatosis and gallstone
      formation. Patients should be monitored by screening liver enzymes and abdominal
      ultrasonography in order to detect these side effects.

PMID- 27866087
TI  - A predictive model for estimating regional skeletal muscle size by two-point
      dixon magnetic resonance imaging in healthy Koreans.
AB  - This study was undertaken to develop and cross-validate reference and individual
      predictive models for estimating functional thigh muscle cross-sectional area
      (TCSA) by 2-point Dixon magnetic resonance imaging (MRI). TCSAs of dominant sides
      at the mid-thigh level were measured by 2-point Dixon MRI (MRITCSA). Functional
      MRITCSA were compared with the predictive models in a sample of 92 younger (20-40
      years; 28.55+/-4.87; n=50) and older (>65years; 71.22+/-4.82; n=42) Koreans. Lean
      body masses were measured by dual energy X-ray absorptiometry (DXALBM), and thigh
      isokinetic muscle strengths, extension peak torque at 60 degrees /sec, were
      measured using a Biodex(r) dynamometer (BiodexEPT). Multiple regression analysis
      generated the reference model (R2=0.75 and SEE=1472.63mm2 (8%)) as follows: The
      reference model: functional TCSA(mm2)=-1230.49+62.81*height+3061.78*gender 
      2692.57*age+58.91*weight. The individual model (R2=0.80, SEE=1158.34mm2 (7%)) was
      as follows: The individual model: functional TCSA(mm2)=1631.62+1.76*
      DXALBM+9.51*BiodexEPT where height is in centimeters; weight is in kilograms; for
      gender, female=0 and male=1; and for age, age under 40=1 and age over 65=2. PRESS
      statistics of R2 and SEE were 0.78 and 1382.98mm2 for the reference model, and
      0.88 and 979.02mm2 for the individual model. The 2-point Dixon MRI appears to be
      valid for measuring functional muscle size. Our results suggest that the
      reference and individual models provide acceptable estimates of functional thigh
      muscle CSA in healthy Korean adults. Therefore, the models developed in the study
      could be useful as a research tool to establish indexes for functional muscle
      composition in healthy Koreans.

PMID- 27866089
TI  - Absence of epithelial atypia in B3-lesions of the breast is associated with
      decreased risk for malignancy.
AB  - INTRODUCTION: Lesions of uncertain malignant potential (B3) represent a
      heterogeneous group with an overall risk for malignancy of 9.85-35.1% after total
      resection. Positive predictive values (PPV) for malignancy vary depending on B3
      subtype. The aim of this study was to evaluate the PPV for malignancy in B3
      lesions and to determine the clinical significance of atypia-dependent sub
      classification (a = without epithelial atypia; b = with epithelial atypia) of B3
      into B3a and B3b and papillary lesions (PL) in PLa and PLb. METHODS: 219 patients
      with histopathologically proven B3 lesions on core needle/vacuum-assisted biopsy
      who subsequently underwent diagnostic excision biopsy were included in this
      study. PPVs for malignancy were reported for B3 in general and all B3 sub
      categories. Logistic regression analysis identified associations between B3
      subgroups and outcome after excision biopsy as well as the impact of clinical and
      diagnostic findings on excision diagnosis. RESULTS: The overall PPV rate was
      10.0% (22/219). Excision histology exhibited a higher malignancy rate in PLb
      (2/7; PPV: 28.6%) than in PLa (6/127; PPV: 4.7%) (p = 0.057) and in B3b (12/50;
      PPV: 24.0%) compared to B3a category (8/165; PPV: 4.8%) (p < 0.001). DISCUSSION:
      These findings support the necessity of B3 lesion sub-classification into B3a and
      B3b and of PL into PLa and PLb when considering epithelial atypia. The
      determination of atypia status represents a relevant factor in risk
      stratification for clinical management of B3 lesions. Should future studies using
      the sub-classification of PL confirm these results, observation may be a safe
      option for the clinical management of patients with asymptomatic PLa lesions.

PMID- 27866090
TI  - Relationship between anxiety disorders and domains of health related quality of
      life among Nigerians with breast cancer.
AB  - PURPOSE: Health Related Quality of life (HRQoL) is increasingly recognised as an
      important indicator of outcome and well-being in oncology care. We set out in
      this study to evaluate whether significant association exists between anxiety
      disorders (ADs) and HRQoL in breast cancer, such that any intervention addressing
      ADs would potentially improve HRQoL. METHODS: A cross sectional evaluation of 200
      attendees of an oncology clinic was done using designed questionnaire to gather
      socio-demographic and clinical data. Subsequently, the Schedule for clinical
      Assessment in Neuropsychiatry was used to ascertain ADs and the European
      Organization for Research and Treatment of Cancer QOL Questionnaire (THE EORTC
      QLQ-C30) Version 3 with its breast specific supplement (QLQ-BR-23) was used to
      profile HRQoL in participants. RESULTS: The mean age of participants was 49.6(+/
      11.2) years, and 54% of participants had stage III and IV breast cancer. Findings
      on EORTC QLQ-C30 following univariate analyses showed association between ADs and
      poorer mean scores on global health status, functional domains including
      physical, emotional, social, and cognitive functions (p < 0.05). On the symptom
      scale, those with ADs had higher symptom load including fatigue, pain, insomnia,
      appetite loss, diarrhoea and financial difficulties (p < 0.05). Similarly, the
      QLQ-BR-23 showed correlation between ADs and poorer mean scores on breast cancer
      specific issues like body image, future perspectives, sexual functioning, sexual
      enjoyment, systemic therapy side-effects, upset by hair loss and breast symptoms
      (p < 0.05). Findings after controlling for age, treatment, cancer duration,
      recurrence and stage showed the same pattern of relationship between ADs and
      HRQoL; however, the global health status, cognition, sexual functioning, and
      higher symptom load with respect to appetite loss and financial difficulties were
      not independently related with ADs. CONCLUSIONS: Scaling up of oncological
      services, supportive care and targeted psychosocial interventions are indicated
      for optimal outcome of breast cancer. Longitudinal research with focus on the
      complex relationship between HRQoL and ADs along with their modifiable
      determinants across the trajectories of breast cancer is warranted.

PMID- 27866091
TI  - A sensitivity and specificity comparison of fine needle aspiration cytology and
      core needle biopsy in evaluation of suspicious breast lesions: A systematic
      review and meta-analysis.
AB  - PURPOSE: Breast cancer detections for women with suspicious lesions mainly depend
      on two non-operative pathological tests-fine needle aspiration cytology (FNAC)
      and core needle biopsy (CNB). The aim of this systematic review was to compare
      the sensitivity and specificity of CNB and FNAC in this setting. METHODS: The
      data sources included MEDLINE, EMBASE, PubMed, and the Cochrane Central Register
      of Controlled Trials (CENTRAL) till February 2016. We included prospective series
      of studies which directly compared the accuracy of FNAC and CNB. We used forest
      plots to display the sensitivity and specificity of FNAC and CNB respectively.
      Pre-specified subgroup analyses and sensitivity analysis were conducted. RESULTS:
      Ultimately, 12 articles (1802 patients) were included in the final analysis. The
      pooled analysis shows that the sensitivity of CNB is better than that of FNAC
      [87% (95% CI, 84%-88%, I2 = 88.5%) versus 74% (95% CI, 72%-77%, I2 = 88.3%)] and
      the specificity of CNB is similar to that of FNAC [98% (95% CI, 96%-99%, I2 =
      76.2%) versus 96% (95% CI, 94%-98%, I2 = 39.0%)]. For subgroup analysis, the
      sensitivities of both tests are better for palpable lesions than that of non
      palpable lesions. Sensitivity analysis shows the robustness of the primary
      analysis. CONCLUSION: Our study suggests that both of FNAC and CNB have good
      clinical performance. In similar circumstances, the sensitivity of CNB is better
      than that of FNAC, while their specificities are similar. FNAC could be still
      considered the first choice to evaluate suspicious nonpalpable breast lesions.

PMID- 27866092
TI  - Identify high risk estrogen receptor-positive breast cancer patients for extended
      endocrine therapy.
AB  - PURPOSE: To demonstrate the patterns of breast cancer-specific mortality (BCSM)
      in estrogen receptor (ER)-positive diseases and to identify high-risk candidates
      for extended endocrine therapy. METHODS: Using the Surveillance, Epidemiology and
      End Results database, we identified ER-positive patients diagnosed between 1990
      and 2000 (cohort 1 [C1]) and between 2001 and 2005 (cohort 2 [C2]). The patterns
      of BCSM were calculated using Cox proportional hazard regression models. A risk
      classification model was developed, and X-tile software was used to divide
      patients with high BCSM rates into 3 risk groups. RESULTS: The annual BCSM rate
      of C2 was decreased by one-third and was maintained at 10-15 (per 1000 persons
      per year) from year 2 to year 10. Long-term mortality risks still persisted in
      C2, especially in patients with node-positive, grade 3 or T3 disease, who should
      be considered as "clinical-high-risk". These patients were further divided into 3
      risk groups through our model: for C1, 42.2% were in the low-risk group, 38.9% in
      the medium-risk group, and 18.9% in the high-risk group; and for C2, 45.5% were
      in the low-risk group, 38.2% in the medium-risk group and 16.2% in the high-risk
      group (p < 0.001). The BCSM rates of the patients in each group within C2
      decreased, and fewer patients in C2 were classified into the clinical high-risk
      group. CONCLUSION: ER-positive patients with node-positive, grade 3 or T3
      diseases had sustained risks of death throughout the 10-year time frame, and our
      model is helpful to identify patients with high risk who are candidates for
      extended endocrine therapy.

PMID- 27866093
TI  - NSCA-1-a novel N-substituted coumalamide derivative-increases Adriamycin
      sensitivity in HepG2/adriamycin cells through modulating Akt/GSK-3beta signaling
      and p53-dependant apoptotic pathway.
AB  - Coumalamide derivatives are one of 2-pyrones derivatives, exerting
      multifunctional bioactivity. An array of coumalamide derivatives have been
      developed and presented good antiproliferative properties on cancer cells.
      However, the synthesis of 5-substituted coumalamide derivatives has not yet been
      published. Resistance to chemotherapeutic drugs is a major obstacle in
      hepatocellular carcinoma therapy. Recent evidence suggests that overexpression of
      constitutively active Akt confers on cancer cells resistance to chemotherapy. In
      this study, we report the synthesis and biological evaluation of a novel N
      substituted coumalamide derivative (NSCA-1). The results indicated that NSCA-1
      exerts synergistic cytotoxicity with Adriamycin in HepG2/ADR (HepG2/adriamycin)
      cells. Furthermore, both of the Akt kinase activity and phosphorylated Akt
      (Ser473) were found to be inhibited by NSCA-1 and subsequently resulting in
      decreased phosphorylation of GSK-3beta. The intracellular accumulation of
      Adriamycin was also boosted by NSCA-1 via reducing the expression of p-gp. In
      addition, we found that combined treatment with NSCA-1 enhance cell apoptosis
      induced by Adriamycin via p53-dependant apoptotic pathway.

PMID- 27866094
TI  - (Neo)adjuvant treatment in localised soft tissue sarcoma: The unsolved affair.
AB  - Soft tissue sarcomas (STS) are rare and heterogeneous tumours. A correct
      definition of STS is imperative from the very beginning of disease management, to
      guide the diagnostic and imaging work-up, and help to establish the prognosis on
      which the therapeutic strategy will be based. Over the last few years, many
      efforts have been made to identify characteristics that could predict disease
      behaviour and to enrich the therapeutic armamentarium against the advanced
      disease, that is still characterised by poor prognosis. Surgery remains the
      milestone of treatment for localised STS, whereas many uncertainties regarding
      the role of adjuvant and neoadjuvant treatment persist. Some controlled evidence
      is available, but often conflicting and insufficient to make chemotherapy (CT) a
      standard practice and, currently, a common and shared strategy does not exist.
      The biggest question concerns the prospective identification of the subgroup of
      patients who would benefit the most from (neo)adjuvant therapies. In light of the
      growing understanding of different biologies and sensitivities of the various
      sarcoma subtypes, the value of histology in the selection of peri-operative
      treatments is one of the most intriguing topics under discussion. In this
      perspective, a new generation of neoadjuvant trials have been planned and are
      currently ongoing. The aim of this review was to rekindle interest in the long
      standing topic of (neo)adjuvant CT in localised STS, providing an update on its
      role in sarcomas' management and highlighting future directions and consequential
      factors needed to further improve outcomes in this disease.

PMID- 27866095
TI  - Continuing EGFR inhibition beyond progression in advanced non-small cell lung
      cancer.
AB  - The majority of patients with epidermal growth factor receptor (EGFR) mutant non
      small cell lung cancer (NSCLC) respond to first-line EGFR tyrosine kinase
      inhibitors (TKIs), but nearly all inevitably acquire resistance and develop
      disease progression. Conventional practice would be to switch treatments to
      second-line therapy. However, continuing TKIs beyond progression is becoming
      increasingly commonplace in patients with indolent, small volume asymptomatic
      growth, who may potentially continue to derive ongoing clinical benefit and to
      avoid a 'withdrawal tumour flare'. Nevertheless, there are limitations to our
      current criteria for assessing disease response, which are based on radiological
      assessments without considering symptomatic benefit, or the complex molecular and
      clinical heterogeneity of tumour growth and drug response patterns. In this
      article, we review the rationale for continuing EGFR inhibitors in patients with
      EGFR mutant NSCLC beyond disease progression and discuss strategies that have
      been pursued in the context of molecularly and clinically heterogeneous
      populations of tumour growth depending on the different clinical scenarios
      encountered. We discuss the management of systemic disease progression, including
      continuing EGFR TKIs alone, introducing a drug holiday, or combining TKIs with
      chemotherapy or other molecularly targeted agents. We also focus on approaches in
      managing patients with indolent, small volume asymptomatic growth (non-CNS
      oligometastatic disease progression) and those with oligometastatic EGFR mutant
      NSCLC with involvement of the central nervous system. We envision future
      precision medicine strategies through the use of next generation sequencing
      strategies of serial tumour rebiopsies and circulating plasma DNA to
      individualise the management for such patients during disease progression.

PMID- 27866096
TI  - Comparative effectiveness and safety of thalidomide and lenalidomide in patients
      with multiple myeloma in the United States of America: A population-based cohort
      study.
AB  - BACKGROUND: The comparative effectiveness of thalidomide and lenalidomide in the
      treatment of multiple myeloma has not been established. We conducted an
      observational cohort study of multiple myeloma patients receiving either
      thalidomide or lenalidomide in routine care in the United States of America to
      assess their comparative survival and rates of peripheral neuropathy. METHODS:
      Myeloma patients were identified and followed using administrative claims data
      from a large national health insurance provider (UnitedHealth). Patients were
      eligible if they initiated treatment with either lenalidomide or thalidomide
      between 2004 and 2013. Propensity score stratified Cox proportional hazards
      regression was used to estimate the hazard ratios (HR) and 95% confidence
      intervals (CI) for death and new-onset peripheral neuropathy (defined by
      International Classification of Disease, Ninth Revision codes or a new
      prescription intended to treat neuropathic pain). FINDINGS: Our cohort included
      1264 myeloma patients who initiated either thalidomide or lenalidomide. Among 406
      new users of thalidomide, 142 (35%) developed peripheral neuropathy during a mean
      499 person-days of follow-up. Among 858 new users of lenalidomide, 244 (29%)
      developed neuropathy during 587 person-days. Compared with thalidomide
      initiators, lenalidomide initiators had a reduced risk of peripheral neuropathy
      (HR 0.71, 95% CI: 0.56-0.92). We found no difference in rates of death (HR 1.00,
      95% CI: 0.71-1.41). INTERPRETATION: Our results agree with the findings of
      recently published trials suggesting that thalidomide and lenalidomide are
      equivalent with respect to survival outcomes but different with respect to
      neurotoxicity in clinical practice settings.

PMID- 27866097
TI  - Current therapy and the evolving molecular landscape of paediatric ependymoma.
AB  - Ependymomas are the third commonest paediatric central nervous system (CNS)
      tumour, accounting for 6-12% of brain tumours in children. The management of
      these tumours has seen considerable changes over the last two decades, leading to
      a significant improvement in outcomes. However, despite advances in
      neurosurgical, neuroimaging and postoperative adjuvant therapy, management of
      these tumours remain challenging, and recurrence occurs in over 50% of cases,
      particularly when complete resection is not achieved prior to conformal
      radiotherapy. To-date no chemotherapeutic regimen has proven to be of significant
      clinical benefit. Predicting tumour behaviour and defining robust correlates of
      disease outcome based on histopathology and clinical characteristics remains
      suboptimal. Paucity of cell lines, failure to develop ideal animal models of
      these tumours, have precluded better understanding of the oncogenic drivers,
      undermining development of targeted therapies. Over the last few years
      breakthrough in the understanding of the molecular biology, are now providing
      clues to therapeutic insights. It is clear that even with histopathological
      similarities, these are genetically heterogeneous tumours with diverse clinical
      outcomes. Rapid evolution of data based on genome-wide DNA methylation patterns,
      have now identified nine molecular subgroups in these tumours, across three
      anatomic compartments which include supratentorial (ST), posterior fossa (PF) and
      the spinal locations. More recently based on transcriptome profiling, two
      subgroups (group A and B) of PF ependymoma have been identified with distinct
      molecular, clinical characteristics and specific chromosomal aberrations. This
      review includes current management, evolving molecular biology and the shifting
      paradigm of treatment profile that targets molecular alterations in paediatric
      ependymoma.

PMID- 27866098
TI  - Study on the relationship of genotoxic and oxidative potential of a new mixed
      chelate copper antitumoral drug, Casiopeina II-gly (Cas II-gly) in Drosophila
      melanogaster.
AB  - The present study evaluates the superoxide dismutase (SOD) and catalase (CAT)
      activities in a wild strain of Drosophila melanogaster and the genotoxic
      potential induced by Cas II-gly (a new antineoplastic drug) using the somatic
      mutation and recombination test. Larvae 48h old were treated with Cas II-gly in a
      range of 0-1.5mM and aliquot were taken every 24h to have individuals treated for
      24, 48, 72h and adulthood as well. A dose-dependent toxicity and a significant
      increase in SOD and CAT activities were found after a 24 and 48h treatment with
      0.5-1.5mM concentrations. The comparison of the effect in enzymes with mutation
      indicated a positive correlation with increased genetic damage, after 24 and 48h
      of exposure for all concentrations tested. The addition of the genetic damage
      induced in each exposure time showed a significant effect, but only the small
      single spots had a concentration-related increase.

PMID- 27866099
TI  - How to image cell adhesion on soft polymers?
AB  - Here, we present a method to investigate cell adhesion on soft, non-conducting
      polymers that are implant candidate materials. Neuronal cells were grown on two
      elastomers (polydimethylsiloxane (PDMS) and Ecoflex(r)) and prepared for electron
      microscopy. The samples were treated with osmium tetroxide (OsO4) and
      uranylacetate (UrAc). Best results can be achieved when the polymers were coated
      with a thin iridium layer before the cell culture. This was done to emphasize the
      usage of soft polymers as supports for implant electrodes. A good contrast and
      the adhesion of the cells on soft polymers could be visualized.

PMID- 27866100
TI  - TEM illumination settings study for optimum spatial resolution and indexing
      reliability in crystal orientation mappings.
AB  - The spatial resolution and the indexing quality obtained with an automated
      orientation and phase mapping tool are analyzed for different Transmission
      Electron Microscope (TEM) illumination settings. The electron probe size and
      convergence angle are studied for two TEM configuration modes referred as
      microprobe and nanoprobe modes. Using a 10MUmC2 aperture in a FEI Tecnai F20
      (S)TEM, the nanoprobe mode is used to get a small convergent electron beam while
      the microprobe mode provides a nearly parallel illumination at the cost of a
      larger probe size. The nanoprobe configuration enables to increase the spatial
      resolution (~1nm vs 3nm) but also affects the fraction of mis-indexed points (15%
      vs 1%). Indexing errors are attributed to the increase by a factor of three of
      the convergence angle with respect to the microprobe mode. While intermediate
      optimum settings may be found and are potentially achievable on electron
      microscopes providing a 'free lens' control or a larger choice of C2 apertures,
      it is emphasized that the spatial resolution cannot be considered without
      reference to the indexing quality and, consequently to the convergence angle.

PMID- 27866101
TI  - Decadal phytoplankton dynamics in response to episodic climatic disturbances in a
      subtropical deep freshwater ecosystem.
AB  - Information of the decadal timescale effects of episodic climatic disturbances
      (i.e., typhoons) on phytoplankton in freshwater ecosystems have received less
      attention and fewer seasonal evaluations partly due to the lack of long-term time
      series monitoring data in typhoon prevailing areas. Through field observations of
      a total 36 typhoon cases in a subtropical deep freshwater ecosystem in the period
      of 2005-2014, we quantified phytoplankton biomass, production and growth rate in
      response to meteorological and hydrological changes in the weeks before, during
      and after typhoons between summer and autumn, and also investigated the effects
      of typhoon characteristics on the aforementioned phytoplankton responses. The
      results showed that phytoplankton exposed to typhoon disturbances generally
      exhibited an increasing trend over the weeks before, during and after typhoons in
      summer but varied in autumn. The correlations and multivariate regressions showed
      different contributions of meteorological and hydrological variables to
      individual phytoplankton responses before, during and after typhoons between
      seasons. The post-typhoon weeks (i.e., within two weeks after a typhoon had
      passed) were especially important for the timeline of phytoplankton increases and
      with a detectable seasonal variation that the chlorophyll a concentration
      significantly increased in autumn whereas both primary production and growth rate
      were associated with significant changes in summer. Additionally, phytoplankton
      responses during the post-typhoon weeks were significantly different between
      discrete or continuous types of typhoon events. Our work illustrated the fact
      that typhoons did influence phytoplankton responses in the subtropical deep
      freshwater ecosystem and typhoon passages in summer and autumn affected the
      phytoplankton dynamics differently. Nevertheless, sustained and systematic
      monitoring in order to advance our understanding of the role of typhoons between
      seasons in the modulation of phytoplankton productivity and functioning is
      required because such episodic climatic disturbances are projected to have
      intense magnitude and inconsistent frequency under 21st century climate change.

PMID- 27866102
TI  - Variations in physical, chemical and biological properties in relation to sludge
      dewaterability under Fe (II) - Oxone conditioning.
AB  - The mechanism of Fe (II) - oxone conditioning to improve sludge dewaterability
      was investigated in this study. Five different types of sludge were tested,
      including raw sludge (Group 1: mixed primary and secondary sludge, waste
      activated sludge and anaerobic digested sludge) and pretreated sludge with prior
      solubilisation (Group 2: ultrasonic or thermal pretreated sludge). After Fe (II) 
      oxone conditioning, the concentrations of dissolved organic carbon, protein and
      polysaccharide of soluble extracellular polymeric substances (SB EPS) increased
      for Group 1, but decreased for Group 2. For all types of sludge investigated, the
      related organic compounds of loosely bound (LB) and tightly bound (TB) EPS
      decreased with Fe (II) - oxone conditioning, and increased sludge filterability
      showed strong and positive correlation with the removal of low molecular weight
      protein and neutrals in LB EPS. Fe (II) - oxone was very effective in
      disintegrating cell membrane and caused potential cell lysis, as indicated by
      increased percentage of damaged microbial cells. From this study, the mechanism
      of Fe (II) - oxone conditioning was proposed and can be divided into two steps:
      (1) Oxidation step - sulfate radicals degraded organic compounds in LB and TB EPS
      in sludge and transformed bound water to free water that was trapped in TB and LB
      EPS; It also damaged cells membrane and may help to release intracellular water
      content. Sludge flocs were broken into smaller particles; (2) Coagulation step -
      Fe (III), generated from the oxidation step can act as a coagulant to agglomerate
      smaller particles into larger ones and reduce the repulsive electrostatic
      interactions. Combined effects from above two steps can greatly improve sludge
      filterability.

PMID- 27866104
TI  - Aquatic transformation of phosphite under natural sunlight and simulated
      irradiation.
AB  - The phototransformation of phosphite (HPO32-, H2PO3-, +3) from Lake Taihu water
      (THW) under natural sunlight was evaluated. No direct phosphite photoreaction was
      observed under sunlight. Suspended solids were shown to play important roles in
      the indirect photoreaction of phosphite in lake water. The phototransformation of
      phosphite followed pseudo-first-order reaction kinetics and the kinetics
      constants (k, d-1) decreased as: 0.0324 (original THW), 0.0236 (sterilized THW),
      0.0109 (filtered THW) and 0.0102 (sterilized filtered THW). Original THW with 1
      mmol L-1 NO3- added was used to simulate the phosphite removal in lakes with
      serious N pollution. The results showed that the phototransformation was
      accelerated (with k increased to 0.0386-0.0463 d-1), and sterilization or
      filtration shown little effect to the transformation, as the half-lives of
      phosphite drew closer. Under simulated irradiation in NO3- system, increasing NO3
      concentration or decreasing pH value promoted phototransformation. The addition
      of Fe3+ or Fe2+ accelerated photooxidation, while the addition of Mn2+ or Cd2+
      inhibited phototransformation. Br-, NO2- and HCO3- in environmental
      concentrations decreased phototransformation, and HCO3- showed the strongest
      inhibition. Suwannee River humic acid or Suwannee River fulvic acid strongly
      inhibited the photooxidation process, and the inhibiting effects varied with
      their structure. Phosphite photooxidation was strongly inhibited by adding
      isopropanol or sodium azide as reactive oxygen species (ROS) quenchers. Electron
      spin resonance analysis indicated that OH was a main oxidant produced in this
      system. The increased amount of phosphate coincided with the decreased amount of
      phosphite, which indicated that the transformation product of phosphite was
      phosphate. Phosphite is a considerable component of the P redox cycle in Lake
      Taihu.

PMID- 27866103
TI  - Enhanced MFC power production and struvite recovery by the addition of sea salts
      to urine.
AB  - Urine is an excellent fuel for electricity generation in Microbial Fuel Cells
      (MFCs), especially with practical implementations in mind. Moreover, urine has a
      high content in nutrients which can be easily recovered. Struvite (MgNH4PO4.6H2O)
      crystals naturally precipitate in urine, but this reaction can be enhanced by the
      introduction of additional magnesium. In this work, the effect of magnesium
      additives on the power output of the MFCs and on the catholyte generation is
      evaluated. Several magnesium sources including MgCl2, artificial sea water and a
      commercially available sea salts mixture for seawater preparation (SeaMix) were
      mixed with real fresh human urine in order to enhance struvite precipitation. The
      supernatant of each mixture was tested as a feedstock for the MFCs and it was
      evaluated in terms of power output and catholyte generation. The commercial
      SeaMix showed the best performance in terms of struvite precipitation, increasing
      the amount of struvite in the solid collected from 21% to 94%. Moreover, the
      SeaMix increased the maximum power performance of the MFCs by over 10% and it
      also changed the properties of the catholyte collected by increasing the pH,
      conductivity and the concentration of chloride ions. These results demonstrate
      that the addition of sea-salts to real urine is beneficial for both struvite
      recovery and electricity generation in MFCs.

PMID- 27866105
TI  - Pilot-scale removal and recovery of dissolved phosphate from secondary wastewater
      effluents with reusable ZnFeZr adsorbent @ Fe3O4/SiO2 particles with magnetic
      harvesting.
AB  - Advanced nanocomposite magnetic particles functionalized with ZnFeZr-adsorbent
      are developed, characterized and tested for the removal and recovery of phosphate
      directly from spiked secondary wastewater effluent (~10 mg/L PO4-P). The
      phosphate loaded particles can be extracted from the liquid phase via magnetic
      separation, regenerated in a NaOH solution where phosphate desorption takes
      place, and reused in numerous cycles. Laboratory experiments demonstrate their
      reusability and stability in 60 consecutive adsorption/desorption runs where
      under optimal conditions > 90% total P-recovery efficiency is reached. In
      addition, pilot tests are performed to verify the proof-of-concept by upscaling
      the technology and maintain high efficiency of phosphate removal and recovery
      after treating 1.5 m3 wastewater in 20 cycles. Effluent concentrations <0.05 mg/L
      PO4-P can be achieved in the treated wastewater. The reclaimed desorption
      solution is concentrated with phosphate ions through its repetitive application,
      attaining up to 38-times enrichment (~380 mg/L PO4-P) compared to the initial
      concentration in wastewater. The P-rich eluate is used as a source for subsequent
      precipitation of a solid fertilizer product such as struvite.

PMID- 27866106
TI  - Denitrification in an integrated bioelectro-photocatalytic system.
AB  - Since nitrate causes severe ecological and health risks, nitrate contamination of
      drinking water sources has become one of the most important water quality
      concerns all over the world. Photocatalytic reduction of nitrate to molecular
      nitrogen presents a promising approach to remove nitrate from drinking water
      sources. However, harmful intermediates like NO2-, NO, NO2 and N2O are usually
      formed, and metal loading or hole scavengers are generally needed to reduce the
      recombination of photo-generated electrons and holes, which will cause secondary
      pollution to drinking water. In this work, an efficient, selective and
      sustainable bioelectro-photocatalytic nitrate-reducing system by utilizing
      commercial TiO2 nanoparticles P25 as the photocatalyst and bio-electrons from
      microbial metabolism as the hole scavenger is reported. In this system, bio
      electrons extracted from organic substrates in bioanode are transferred to the
      photocathode through an external circuit for hole quenching. With the utilization
      of the residual photogenerated electrons, nitrate is completely reduced to
      nitrogen without accumulation of harmful nitrite or ammonium. The experimental
      results and the mechanistic analysis using the first-principles density
      functional theory calculations demonstrate that toxic by-products like nitrite or
      ammonium will not be accumulated in this system. Thus, this approach has a great
      potential for sustainable remediation of nitrate-contaminated drinking water
      sources.

PMID- 27866107
TI  - Perturbation-free measurement of in situ di-nitrogen emissions from
      denitrification in nitrate-rich aquatic ecosystems.
AB  - Increased production of reactive nitrogen (Nr) from atmospheric di-nitrogen (N2)
      has greatly contributed to increased food production. However, enriching the
      biosphere with Nr has also caused a series of negative effects on global
      ecosystems, especially aquatic ecosystems. The main pathway converting Nr back
      into the atmospheric N2 pool is the last step in the denitrification process.
      Despite several attempts, there is still a need for perturbation-free methods for
      measuring in situ N2 fluxes from denitrification in aquatic ecosystems at the
      field scale. Such a method is needed to comprehensively quantify the N2 fluxes
      from aquatic ecosystems. Here we observed linear relationships between the
      delta15N-N2O signatures and the logarithmically transformed N2O/(N2+N2O) emission
      ratios. Through independent measurements, we verified that the perturbation-free
      N2 flux from denitrification in nitrate-rich aquatic ecosystems can be inferred
      from these linear relationships. Our method allowed the determination of field
      scale in situ N2 fluxes from nitrate-rich aquatic ecosystems both with and
      without overlaying water. The perturbation-free in situ N2 fluxes observed by the
      new method were almost one order of magnitude higher than those by the sediment
      core method. The ability of aquatic ecosystems to remove Nr may previously have
      been severely underestimated.

PMID- 27866108
TI  - Clinical characteristics of critically ill patients with suspected influenza
      during the 2009-10 and 2013-14 outbreaks.
AB  - PURPOSE: Pandemic influenza A pdm09 (pH1N1) virus was the predominant isolate
      identified during the 2009-10 and 2013-14 influenza outbreaks, causing
      significant morbidity and mortality. We describe clinical characteristics of
      critically ill patients during 2 pH1N1 outbreaks. METHODS: Single-center,
      retrospective cohort study of patients admitted to the intensive care unit
      receiving oseltamivir for suspected influenza during 2 outbreak periods.
      Demographics and comorbidities were collected from the medical record. Outcomes
      included use of adjunct oxygenation therapies and oseltamivir dosing. RESULTS:
      One hundred twenty-four patients were included (2009, n=53; 2013, n=71).
      Demographics were as follows: mean (SD) age, 52.3 (14.2) years; mean (SD) Acute
      Physiology and Chronic Health Evaluation II score, 19.4 (9.2); 71% had greater
      than or equal to 2 comorbidities; and mortality was 27%. Inhaled nitric oxide was
      administered more commonly in 2009 (P=.01), whereas neuromuscular blockade
      (P=.02) and epoprostenol were administered more commonly in 2013 (P=.01).
      Patients in 2009 were more likely to receive high-dose oseltamivir (P=.02; odds
      ratio, 1.8; 95% confidence interval, 1.18-6.62). No differences in clinical
      outcomes were observed between 2009 and 2013. CONCLUSIONS: Use of adjunct
      oxygenation therapies and nontraditional antiviral dosing has changed
      significantly since the 2009 pandemic, although this has not resulted in a
      measurable impact on clinical outcomes.

PMID- 27866109
TI  - Magnitude of temperature elevation is associated with neurologic and survival
      outcomes in resuscitated cardiac arrest patients with postrewarming pyrexia.
AB  - PURPOSE: Avoidance of pyrexia is recommended in resuscitation guidelines,
      including after treatment with targeted temperature management (TTM). Which
      aspects of postresuscitation pyrexia are harmful and modifiable have not been
      conclusively determined. MATERIALS AND METHODS: This retrospective multicenter
      registry study collected serial temperatures during 72 hours postrewarming to
      assess the relationship between 3 aspects of pyrexia (maximum temperature,
      pyrexia duration, timing of first pyrexia) and neurologic outcome (primary) and
      survival (secondary) at hospital discharge. Adult TTM-treated patients from 13 US
      hospitals between 2005 and 2015 were included. RESULTS: One hundred seventy-nine
      of 465 patients had at least 1 temperature greater than or equal to 38 degrees C.
      Pyrexic temperatures were associated with better survival than nonpyrexic
      temperatures (adjusted odds ratio [aOR], 1.54; 95% confidence interval [CI], 1.00
      2.35). Higher maximum temperature was associated with worse outcome (neurologic
      aOR, 0.30 [95% CI, 0.10-0.84]; survival aOR, 0.25 [95% CI, 0.10-0.59]) in pyrexic
      patients. There was no significant relationship between pyrexia duration and
      outcomes unless duration was calculated as hours greater than or equal to 38.8
      degrees C, when longer duration was associated with worse outcomes (neurologic
      aOR, 0.86 [95% CI, 0.75-1.00]; survival aOR, 0.82 [95% CI, 0.72-0.93]).
      CONCLUSIONS: In postarrest TTM-treated patients, pyrexia was associated with
      increased survival. Patients experiencing postrewarming pyrexia had worse
      outcomes at higher temperatures. Longer pyrexia duration was associated with
      worse outcomes at higher temperatures.

PMID- 27866111
TI  - High-fidelity simulation: Teaching end-of-life care.
AB  - The American Nurses Association, American Association of Colleges of Nursing, and
      the Institute of Medicine of the National Academies are unified in the position
      that nursing education must prepare students to coordinate and perform end-of
      life (EOL) care. Yet, according to literature, undergraduate nursing education in
      EOL care remains inadequate. Following a review of literature indicating a need
      for more EOL instruction, a high-fidelity simulation activity is introduced and
      described. Included are guidelines for preparation, role assignment, integration
      of other professionals and family, and student reflection after the activity.
      Student evaluations indicate that the simulation is valuable and improves self
      efficacy in caring for the dying. By providing students with the opportunity to
      experience EOL in a low-risk, learning environment, a high-fidelity EOL
      simulation activity can help educators bridge the knowledge gap in nursing
      education.

PMID- 27866112
TI  - Protein-protein interactions: scoring schemes and binding affinity.
AB  - Protein-protein interactions mediate several cellular functions, which can be
      understood from the information obtained using the three-dimensional structures
      of protein-protein complexes and binding affinity data. This review focuses on
      computational aspects of predicting the best native-like complex structure and
      binding affinities. The first part covers the prediction of protein-protein
      complex structures and the advantages of conformational searching and scoring
      functions in protein-protein docking. The second part is devoted to various
      aspects of protein-protein interaction thermodynamics, such as databases for
      binding affinities and other thermodynamic parameters, computational methods to
      predict the binding affinity using either the three-dimensional structures of
      complexes or amino acid sequences, and change in binding affinities of the
      complexes upon mutations. We provide the latest developments on protein-protein
      docking and binding affinity studies along with a list of available computational
      resources for understanding protein-protein interactions.

PMID- 27866113
TI  - Small world brain network characteristics during EEG Holter recording of a stroke
      event.

PMID- 27866110
TI  - Dysbiosis in the intensive care unit: Microbiome science coming to the bedside.
AB  - Complex microbial communities within the human body, constituting the microbiome,
      have a broad impact on human health and disease. A growing body of research now
      examines the role of the microbiome in patients with critical illness, such as
      sepsis and acute respiratory failure. In this article, we provide an introduction
      to microbiome concepts and terminology and we systematically review the current
      evidence base of the critical-illness microbiome, including 51 studies in animal
      models and pediatric and adult critically ill patients. We further examine how
      this emerging scientific discipline may transform the way we manage infectious
      and inflammatory diseases in intensive care units. The evolving molecular,
      culture-independent techniques offer the ability to study microbial communities
      in unprecedented depth and detail, and in the short-term, may enable us to
      diagnose and treat infections in critical care more precisely and effectively.
      Longer term, these tools may also give us insights in the underlying
      pathophysiology of critical illness and reveal previously unsuspected targets for
      innovative, microbiome-targeted therapeutics. We finally propose a roadmap for
      future studies in the field for transforming critical care from its current
      isolated focus on the host to a more personalized paradigm addressing both human
      and microbial contributions to critical illness.

PMID- 27866114
TI  - Does relative or absolute EEG power have prognostic value in HIE setting?

PMID- 27866115
TI  - Rethinking blinking: No cognitive modulation of reflex eye protection in early
      onset blindness.

PMID- 27866116
TI  - Individuals with chronic hemiparetic stroke can correctly match forearm positions
      within a single arm.
AB  - OBJECTIVE: Previous studies determined, using between arms position matching
      assessments, that at least one-half of individuals with stroke have an impaired
      position sense. We investigated whether individuals with chronic stroke who have
      impairments mirroring arm positions also have impairments identifying the
      location of each arm in space. METHODS: Participants with chronic hemiparetic
      stroke and age-matched participants without neurological impairments (controls)
      performed a between forearms position matching task based on a clinical
      assessment and a single forearm position matching task, using passive and active
      movements, based on a robotic assessment. RESULTS: 12 out of our 14 participants
      with stroke who had clinically determined between forearms position matching
      impairments had greater errors than the controls in both their paretic and non
      paretic arm when matching positions during passive movements; yet stroke
      participants performed comparable to the controls during active movements.
      CONCLUSIONS: Many individuals with chronic stroke may have impairments matching
      positions in both their paretic and non-paretic arm if their arm is moved for
      them, yet not within either arm if these individuals control their own movements.
      SIGNIFICANCE: The neural mechanisms governing arm location perception in the
      stroke population may differ depending on whether arm movements are made
      passively versus actively.

PMID- 27866118
TI  - Pathological and physiological muscle co-activation during active elbow extension
      in children with unilateral cerebral palsy.
AB  - OBJECTIVE: To address the roles and mechanisms of co-activation in two
      flexor/extensor pairs during elbow extension in children with cerebral palsy
      (CP). METHODS: 13 Typically Developing (TD) and 13 children with unilateral
      spastic CP performed elbow extension/flexion at different speeds. Elbow angle and
      velocity were recorded using a 3D motion analysis system. The acceleration and
      deceleration phases of extension were analyzed. Co-activation of the
      brachioradialis/triceps and biceps/triceps pairs was computed for each phase from
      surface electromyographic signals. Statistical analysis involved linear mixed
      effects models and Spearman rank correlations. RESULTS: During the acceleration
      phase, there was strong co-activation in both muscle pairs in the children with
      CP, which increased with speed. Co-activation was weak in the TD children and it
      was not speed-dependent. During the deceleration phase, co-activation was strong
      and increased with speed in both groups; co-activation of brachioradialis/triceps
      was stronger in children with CP, and was negatively correlated with extension
      range and positively correlated with flexor spasticity. CONCLUSIONS: Abnormal
      patterns of co-activation in children with CP were found throughout the entire
      movement. Co-activation was specific to the movement phase and to each flexor
      muscle. SIGNIFICANCE: Co-activation in children with CP is both physiological and
      pathological.

PMID- 27866117
TI  - Distinguishing spinocerebellar ataxia with pure cerebellar manifestation from
      multiple system atrophy (MSA-C) through saccade profiles.
AB  - OBJECTIVE: Patients with spinocerebellar ataxia with pure cerebellar presentation
      (SCD) and multiple system atrophy (MSA-C) show similar symptoms at early stages,
      although cerebellofugal pathology predominates in SCD, and cerebellopetal
      pathology in MSA-C. We studied whether saccade velocity profiles, which reflect
      the accelerating and braking functions of the cerebellum, can differentiate these
      two disorders. METHODS: We recorded visually guided (VGS) and memory guided
      saccades (MGS) in 29 MSA-C patients, 12 SCD patients, and 92 age-matched normal
      subjects, and compared their amplitude, peak velocity and duration (accelerating
      and decelerating phases). RESULTS: Hypometria predominated in VGS and MGS of MSA
      C, whereas hypometria was less marked in SCD, with hypermetria frequently noted
      in MGS. Peak velocity was reduced, and deteriorated with advancing disease both
      in SCD and MSA-C groups at smaller target eccentricities. The deceleration phase
      was prolonged in SCD compared to MSA-C and normal groups at larger target
      eccentricities, which deteriorated with advancing disease. CONCLUSION: Saccades
      in MSA-C were characterized by a more prominent acceleration deficit and those in
      SCD by a more prominent braking defect, possibly caused by the cerebellopetal and
      cerebellofugal pathologies, respectively. SIGNIFICANCE: Saccade profiles provide
      important information regarding the accelerating and braking signals of the
      cerebellum in spinocerebellar ataxia.

PMID- 27866121
TI  - Isotopic composition analysis of dilute Pu solutions using 90-105keV region of
      gamma ray spectra.
AB  - Isotopic composition of dilute Pu solutions (1-3900MUg/mL) has been determined by
      analysis of HPGe detector response function in the 90-105keV region of gamma ray
      spectra. Results are in excellent agreement with that obtained from mass
      spectrometric measurements. The present method has been successfully applied for
      samples of low Pu concentrations, which otherwise is not possible using the
      conventional 120-415keV region of plutonium gamma ray spectra.

PMID- 27866120
TI  - Evidence-based guidelines on the therapeutic use of transcranial direct current
      stimulation (tDCS).
AB  - A group of European experts was commissioned by the European Chapter of the
      International Federation of Clinical Neurophysiology to gather knowledge about
      the state of the art of the therapeutic use of transcranial direct current
      stimulation (tDCS) from studies published up until September 2016, regarding
      pain, Parkinson's disease, other movement disorders, motor stroke, poststroke
      aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's
      disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence
      based analysis included only studies based on repeated tDCS sessions with sham
      tDCS control procedure; 25 patients or more having received active treatment was
      required for Class I, while a lower number of 10-24 patients was accepted for
      Class II studies. Current evidence does not allow making any recommendation of
      Level A (definite efficacy) for any indication. Level B recommendation (probable
      efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1)
      (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left
      dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in
      major depressive episode without drug resistance; (iii) anodal tDCS of the right
      DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation
      (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral
      to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic
      pain secondary to spinal cord lesion. Conversely, Level B recommendation
      (probable inefficacy) is conferred on the absence of clinical effects of: (i)
      anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in
      tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode)
      in drug-resistant major depressive episode. It remains to be clarified whether
      the probable or possible therapeutic effects of tDCS are clinically meaningful
      and how to optimally perform tDCS in a therapeutic setting. In addition, the easy
      management and low cost of tDCS devices allow at home use by the patient, but
      this might raise ethical and legal concerns with regard to potential misuse or
      overuse. We must be careful to avoid inappropriate applications of this technique
      by ensuring rigorous training of the professionals and education of the patients.

PMID- 27866123
TI  - Effect of a dual-purpose cask payload increment of spent fuel assemblies from
      VVER 1000 Bushehr Nuclear Power Plant on basket criticality.
AB  - Dual-purpose casks can be utilized for dry interim storage and transportation of
      the highly radioactive spent fuel assemblies (SFAs) of Bushehr Nuclear Power
      Plant (NPP). Criticality safety analysis was carried out using the MCNP code for
      the cask containing 12, 18, or 19 SFAs. The basket materials of borated stainless
      steel and Boral (Al-B4C) were investigated, and the minimum required receptacle
      pitch of the basket was determined.

PMID- 27866119
TI  - Group III/IV locomotor muscle afferents alter motor cortical and corticospinal
      excitability and promote central fatigue during cycling exercise.
AB  - OBJECTIVE: To investigate the influence of group III/IV muscle afferents on the
      development of central fatigue and corticospinal excitability during exercise.
      METHODS: Fourteen males performed cycling-exercise both under control-conditions
      (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg
      muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was
      used to monitor cortical versus spinal excitability. RESULTS: While fentanyl
      blockade during non-fatiguing cycling had no effect on motor-evoked potentials
      (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13+/-3% higher
      (P<0.05), resulting in a decrease in MEP/CMEP (P<0.05). Although the pre- to post
      exercise reduction in resting twitch was greater in FENT vs. CTRL (-53+/-3% vs. 
      39+/-3%; P<0.01), the reduction in voluntary muscle activation was smaller (-2+/
      2% vs. -10+/-2%; P<0.05). Compared to the start of fatiguing exercise, MEPs and
      CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP
      increased 13+/-3% and 25+/-6% in FENT (P<0.05). CONCLUSION: During non-fatiguing
      exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal
      motoneurons and facilitate motor cortical cells. In contrast, during exhaustive
      exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex
      and promote central fatigue. SIGNIFICANCE: Group III/IV muscle afferents
      influence corticospinal excitability and central fatigue during whole-body
      exercise in humans.

PMID- 27866122
TI  - Synthesis, characterization and radiolabeling of folic acid modified
      nanostructured lipid carriers as a contrast agent and drug delivery system.
AB  - Nanostructured lipid carriers (NLCs) are the new generation of solid lipid drug
      delivery systems. Their suitability as contrast agents for gamma scintigraphy is
      an attracting major attention. The aim of current study was to prepare surface
      modified nanostructured lipid carrier system for paclitaxel (PTX) with active
      targeting and imaging functions. In accordance with the purpose of study, PTX
      loaded nanostructured lipid carriers (NLCs) prepared, modified with a folate
      derivative and radiolabeled with technetium-99m tricarbonyl complex
      (99mTc(CO)3+). Cellular incorporation ratios of radiolabeled nanoparticles
      (99mTc(CO)3-PTX-NLC) were investigated in vitro on three cancer cell lines.
      Additionally in vivo animal studies conducted to evaluate biological behavior of
      99mTc(CO)3-PTX-NLC on female Wistar Albino rats. Biodistribution results showed
      that the folate derivative modified 99mTc(CO)3-PTX-NLC had considerably higher
      uptake in folate receptor positive organs. The data obtained from present study
      could be useful in the design of biodegradable drug carriers of PTX and folate
      receptor based tumor imaging agents.

PMID- 27866124
TI  - A method for determining Am-241 activity for large area contamination.
AB  - Airborne gamma-ray spectrometry system HELINUCTM is used for different missions.
      Although well-developed for estimation of high energy emitters' activity, it is
      rarely used for low energy emitters. A new method for the determination of Am-241
      activity over extended sites based both on statistical analysis of spectra and
      deconvolution of Am-241 signal with a reference library is presented. Results
      show a lowering of the detection threshold and a good agreement with ground level
      measurements.

PMID- 27866125
TI  - Roles of pre-mRNA splicing and polyadenylation in plant development.
AB  - Plants possess amazing plasticity of growth and development, allowing them to
      adjust continuously and rapidly to changes in the environment. Over the past two
      decades, numerous molecular studies have illuminated the role of transcriptional
      regulation in plant development and environmental responses. However, emerging
      studies in Arabidopsis have uncovered an unexpectedly widespread role for post
      transcriptional regulation in development and responses to environmental changes.
      In this review, we summarize recent discoveries detailing the contribution of two
      post-transcriptional mechanisms, pre-mRNA splicing and polyadenylation, to the
      regulation of plant development, with an emphasis on the control of flowering
      time. We also discuss future directions in the field and new technological
      approaches.

PMID- 27866126
TI  - Peer review at EuroIntervention - a rough guide and an expression of thanks.

PMID- 27866127
TI  - Prevention of coronary microvascular plugging: the next target in STEMI?

PMID- 27866128
TI  - Bleeding in STEMI with staged multivessel PCI: is it truly benign?

PMID- 27866129
TI  - Long-term outcomes after Resolute zotarolimus-eluting stent implantation in
      patients with ST-segment elevation acute myocardial infarction: insights from the
      RESOLUTE All Comers Trial and the RESOLUTE Global Clinical Trial Program.
AB  - AIMS: We examined long-term outcomes after implantation of the Resolute
      zotarolimus-eluting stent (R-ZES) in ST-segment elevation acute myocardial
      infarction (STEMI) patients. METHODS AND RESULTS: We compared long-term outcomes
      of STEMI patients undergoing primary angioplasty <12 hours from symptom onset who
      were randomised to the R-ZES (n=122) or the everolimus-eluting stent (EES, n=158)
      in the RESOLUTE All Comers Trial after propensity score adjustment. The five-year
      cumulative incidence of target lesion failure (TLF) was 7.6% versus 10.4% among
      patients treated with R-ZES versus EES, respectively, (adjusted p=0.304), and
      comprised clinically driven target lesion revascularisation (TLR, 2.5% versus
      2.0%, adjusted p=0.766) and cardiac death/target vessel MI (5.1% versus 9.1%,
      adjusted p=0.123). The five-year cumulative incidence of stent thrombosis was
      0.8% for R-ZES patients versus 1.3% for EES patients (adjusted p=0.868). In the
      RESOLUTE Global Clinical Trial Program, excluding RESOLUTE All Comers, the three
      year cumulative incidence of TLF with R-ZES was 9.8% and comprised 7.0%
      clinically driven TLR and 4.5% cardiac death/target vessel MI. CONCLUSIONS:
      Patients with STEMI who received R-ZES had excellent long-term clinical outcomes
      which were similar to those of patients who received EES.

PMID- 27866130
TI  - Outcomes of stenting extra-small (<=2.25 mm) vessels using the Resolute
      zotarolimus-eluting stent (R-ZES).
AB  - AIMS: We assessed long-term outcomes in patients with extra-small (XS) (<=2.25
      mm) and small vessels (SV) (>2.25-2.75 mm) treated with the Resolute zotarolimus
      eluting stent (R-ZES). METHODS AND RESULTS: Data from eight studies including
      patients with XS or SV were pooled for this analysis. Among 2,141 patients (837
      XS, 1,304 SV), three-year cumulative major adverse cardiac events (15.4% vs.
      11.5%; adj. HR [95% CI]: 1.3 [1.0, 1.7], p=0.12), target lesion failure (12.4%
      vs. 9.3%, adj. HR: 1.1 [0.8, 1.5], p=0.56), and target lesion revascularisation
      (TLR: 6.9% vs. 4.5%, adj. HR 1.4 [0.9, 2.1], p=0.17) were greater in the XS
      cohort but were not significantly different after propensity adjustment. Target
      vessel revascularisation occurred more frequently in XS patients in both
      unadjusted and adjusted analyses (11.2% vs. 7.6%, adj. HR: 1.5 [1.1, 2.1],
      p=0.02). Stent thrombosis was low in both cohorts (1.2% vs. 0.6%, p=0.09). In the
      XS cohort, insulin-dependent diabetics had over twofold higher rates of TLR than
      non-diabetics (13.6% vs. 6.0%, p=0.02). CONCLUSIONS: Long-term lesion-specific
      results among patients with XS vessels treated with the R-ZES were not
      significantly different from those among patients with SV, but specific patients
      with XS vessels (e.g., insulin-dependent diabetics) may remain at high risk for
      TLR.

PMID- 27866131
TI  - Ruptured "non-culprit" in-stent neoatherosclerosis during ST-segment elevation
      acute myocardial infarction.

PMID- 27866132
TI  - A tool for predicting the outcome of reperfusion in ST-elevation myocardial
      infarction using age, thrombotic burden and index of microcirculatory resistance
      (ATI score).
AB  - AIMS: Restoration of effective myocardial reperfusion by primary percutaneous
      coronary intervention (PPCI) in patients with ST-elevation myocardial infarction
      is difficult to predict. A method to assess the likelihood of a suboptimal
      response to conventional pharmacomechanical therapies could be beneficial. We
      aimed to derive and validate a scoring system that can be used acutely at the
      time of coronary reopening to predict the likelihood of downstream microvascular
      impairment in patients with STEMI. METHODS AND RESULTS: A score estimating the
      risk of post-procedural microvascular injury defined by an index of
      microcirculatory resistance (IMR) >40 was initially derived in a cohort of 85
      STEMI patients (derivation cohort). This score was then tested and validated in
      three further cohorts of patients (retrospective [30 patients], prospective [42
      patients] and external [29 patients]). The ATI score (age [>50=1]; pre-stenting
      IMR [>40 and <100=1; >=100=2]; thrombus score [4=1; 5=3]) was highly predictive
      of a post-stenting IMR >40 in all four cohorts (AUC: 0.87; p<0.001-derivation
      cohort, 0.84; p=0.002-retrospective cohort, 0.92; p<0.001-prospective cohort and
      0.81; p=0.006-external cohort). In the whole population, an ATI score >=4
      presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred
      in the presence of an ATI score <2. CONCLUSIONS: The ATI score appears to be a
      promising tool capable of identifying patients during PPCI who are at the highest
      risk of coronary microvascular impairment following revascularisation. This
      procedural risk stratification has a number of potential research and clinical
      applications and warrants further investigation.

PMID- 27866133
TI  - Bleeding episodes in "complete, staged" versus "culprit only" revascularisation
      in patients with multivessel disease and ST-segment elevation myocardial
      infarction: a DANAMI-3-PRIMULTI substudy.
AB  - AIMS: The aim of this study was to evaluate whether a staged in-hospital complete
      revascularisation strategy increases the risk of serious bleeding events in
      patients with ST-segment elevation myocardial infarction (STEMI) and multivessel
      disease. METHODS AND RESULTS: The DANAMI-3-PRIMULTI trial investigated whether a
      staged in-hospital complete revascularisation strategy improved outcome in
      patients with STEMI and multivessel disease. In this substudy, we investigated
      potential bleeding complications related to a second in-hospital procedure.
      Bleedings were assessed using BARC and TIMI criteria. Six hundred and twenty
      seven (627) patients were randomised 1:1 to either PCI of the infarct-related
      artery (IRA) only (n=313) or complete revascularisation during a staged procedure
      before discharge (n=314). We found no significant difference in TIMI major+minor
      bleedings related to the primary PCI. There were neither major nor minor
      bleedings in relation to the second procedure in the complete revascularisation
      arm. There were significantly more in-hospital minimal+medical attention
      bleedings in the group randomised to complete revascularisation (61.5% vs. 49.5%
      in the IRA-PCI only group, p=0.003), but no difference in admission time or one
      year mortality (2.2% complete revascularisation-group vs. 2.6% IRA-PCI only
      group, p=0.8). CONCLUSIONS: In multivessel diseased STEMI patients, a staged
      complete in-hospital revascularisation strategy or any second in-hospital
      procedure did not result in an increase in serious bleeding events.

PMID- 27866134
TI  - One-year clinical outcomes of patients treated with everolimus-eluting
      bioresorbable vascular scaffolds versus everolimus-eluting metallic stents: a
      propensity score comparison of patients enrolled in the ABSORB EXTEND and SPIRIT
      trials.
AB  - AIMS: We sought to compare the outcomes of low/moderate complexity patients
      treated with the Absorb BVS from the ABSORB EXTEND trial with patients treated
      with the XIENCE everolimus-eluting stent (EES), using propensity score (PS)
      matching of pooled data from the SPIRIT trials (SPIRIT II, SPIRIT III, SPIRIT IV)
      and the XIENCE V USA trial. METHODS AND RESULTS: ABSORB EXTEND was a prospective,
      single-arm, open-label clinical study in which 812 patients were enrolled at 56
      sites. This study allowed the treatment of lesions <=28 mm in length and with a
      reference vessel diameter of 2.0-3.8 mm (as assessed by online QCA). The
      propensity score was obtained by fitting a logistic regression model with the
      cohort indicator as the binary outcome and other variables as the predictor
      variables. At one-year clinical follow-up, there was no statistical difference
      between groups with regard to MACE (5.0% vs. 4.8%, p=0.83), target lesion failure
      (5.0% vs. 4.7%, p=0.74), ischaemia-driven target vessel revascularisation (2.3%
      vs. 3.0%, p=0.38) and device thrombosis (1.0% vs. 0.3%, p=0.11). Myocardial
      infarction was higher with Absorb (3.3% vs. 1.5%, p=0.02), at the expense of
      periprocedural CK-MB elevation. Independent predictors of MACE among patients
      receiving Absorb BVS were treatment of multivessel disease, insulin-dependent
      diabetes and performance of post-dilation. CONCLUSIONS: At one-year follow-up,
      propensity score-matched analysis demonstrated that the clinical safety and
      effectiveness of Absorb are comparable to those of XIENCE EES among non-complex
      patients treated with PCI.

PMID- 27866135
TI  - Endothelial dysfunction and the occurrence of radial artery spasm during
      transradial coronary procedures: the ACRA-Spasm study.
AB  - AIMS: The aim of this study was to analyse the relation between endothelial
      dysfunction (ED) and the occurrence of radial artery spasm (RAS) during
      transradial coronary procedures. METHODS AND RESULTS: From May 2014 to June 2015,
      endothelial function was assessed by EndoPAT and FMD before the procedure in 165
      patients referred for coronary angiography or intervention. The primary endpoint
      was RAS, defined by patient's symptoms and procedural characteristics. The mean
      age of the study population was 63 years and 71% were male. In total 16% of the
      patients experienced RAS. The incidence of RAS did not differ between patients
      with and without ED (13.8% vs. 20.2%, OR 0.63, 95% CI: 0.25-1.58, p=0.32). The
      strongest predictors of RAS were a ratio of radial artery inner diameter and
      sheath outer diameter smaller than 1 (OR 4.7, 95% CI: 1.35-16.5, p=0.009) and a
      combination of clinical characteristics presented as an RAS risk score of at
      least 4 (p=0.007, OR 3.7, 95% CI: 1.37-9.89). CONCLUSIONS: Endothelial
      dysfunction was not found to be a predictor of the occurrence of radial artery
      spasm in a cohort of patients undergoing elective heart catheterisation. Radial
      artery-sheath mismatch is the strongest pre-procedural predictor of RAS.

PMID- 27866136
TI  - Biodegradable polymer-based, argatroban-eluting, cobalt-chromium stent (JF-04)
      for treatment of native coronary lesions: final results of the first-in-man study
      and lessons learned.
AB  - AIMS: The aim of the study was to investigate the six-month angiographic and nine
      month clinical follow-up outcomes in a first-in-man study using the biodegradable
      polymer-based cobalt-chromium argatroban-eluting stent (JF-04) for treatment of
      native coronary atherosclerotic lesions. METHODS AND RESULTS: A total of 31
      patients with either stable or unstable angina, or silent myocardial ischaemia,
      exhibiting de novo coronary lesions were enrolled at seven Japanese sites. The
      lesions were treated with the JF-04 stent after predilatation. The primary
      endpoint was angiographic in-stent late loss six months after implantation. The
      secondary endpoints included angiographic restenosis and in-stent volume
      obstruction by intravascular ultrasound at six months and target vessel failure
      (TVF) at nine months. Procedural success was achieved in 100% of cases. At six
      months, angiographic in-stent late loss was 1.01+/-0.48 mm and binary restenosis
      was observed in nine cases (29.0%). Among these restenotic cases, most (n=8)
      demonstrated advanced angiographic restenosis patterns, including
      diffuse/proliferative restenosis and total occlusion. At nine months, TVF was
      observed in four cases (12.9%), exclusively attributed to target vessel
      revascularisation. CONCLUSIONS: This argatroban-eluting stent failed to inhibit
      neointimal hyperplasia sufficiently, despite the theoretical benefits and
      promising clinical experience with local drug delivery.

PMID- 27866137
TI  - Clinical and multimodality imaging results at 6 months of a bioresorbable
      sirolimus-eluting scaffold for patients with single de novo coronary artery
      lesions: the NeoVas first-in-man trial.
AB  - AIMS: The study sought to investigate clinical and multimodality imaging
      assessment of a bioresorbable sirolimus-eluting scaffold (NeoVas, Lepu Medical,
      Beijing, China) for patients with single de novo coronary artery lesions. METHODS
      AND RESULTS: The NeoVas first-in-man study was a prospective, open-label study
      which enrolled 31 patients with single de novo lesions treated with a
      bioresorbable sirolimus-eluting scaffold. The primary endpoint was target lesion
      failure (TLF), a composite of cardiac death, target vessel myocardial infarction
      and clinically indicated target lesion revascularisation (TLR). Angiography,
      intravascular ultrasound (IVUS) and optical coherence tomography (OCT) imaging
      were performed at baseline and six months. Procedural success and device success
      were 100% (31/31 patients). At six months, the rate of TLF was 3.2%, with only
      one patient having clinically indicated TLR. No scaffold thrombosis was observed.
      The angiographic six-month in-scaffold late loss was 0.26+/-0.32 mm. The minimal
      scaffold area decreased from 7.11+/-1.56 mm2 post procedure to 6.74+/-1.38 mm2 at
      six months, as measured by IVUS. The OCT results showed that the neointimal
      hyperplasia area was low (1.56+/-0.46 mm2), with a high proportion of scaffold
      strut coverage (95.7%). CONCLUSIONS: This first-in-man study shows feasibility,
      promising clinical and multimodality imaging results up to six months for the
      NeoVas bioresorbable sirolimus-eluting scaffold in the treatment of patients with
      simple de novo lesions, with an acceptable in-scaffold late loss, low neointimal
      hyperplasia, and a high percentage of scaffold strut coverage.

PMID- 27866138
TI  - Coronary covered stents.
AB  - Covered stents offer an effective bail-out strategy in vessel perforations, are
      an alternative to surgery for the exclusion of coronary aneurysms, and have a
      potential role in the treatment of friable embolisation-prone plaques. The aim of
      this manuscript is to offer an overview of currently available platforms and to
      report results obtained in prior studies.

PMID- 27866139
TI  - Triple orifice as a novel strategy in interventional reconstruction of a mitral
      pseudo cleft.

PMID- 27866140
TI  - One-year outcomes with two suture-mediated closure devices to achieve access-site
      haemostasis following transfemoral transcatheter aortic valve implantation.
AB  - AIMS: In the current study we assess the impact of two different access-site
      suture-mediated closure devices (SMCD), ProGlide and Prostar, on vascular and
      bleeding complications after transfemoral transcatheter aortic valve implantation
      (TAVI), as well as on long-term mortality. METHODS AND RESULTS: From 2008 to
      2013, 1,022 patients underwent transfemoral TAVI in two German centres using
      ProGlide (n=506) and Prostar (n=516) SMCD to close the access site. The primary
      outcome was the incidence of peri-TAVI major vascular complications according to
      Valve Academic Research Consortium-2 (VARC-2) definitions. Secondary outcomes
      were the incidence of bleeding complications and mortality. Compared to the
      Prostar SMCD group, patients in the ProGlide SMCD group less frequently
      experienced VARC-2 major vascular complications (7.5% vs. 15.9%, p<0.001),
      closure device failure (0.8% vs. 2.3%, p=0.04), any bleeding (BARC: 36.8% vs.
      53.9%, p<0.001; VARC-2: 30.8% vs. 34.9%, p=0.59). Furthermore, one-year mortality
      was significantly lower in the ProGlide SMCD group, 14.8% vs. 19.5% in the
      Prostar SMCD group, log-rank p=0.04. However, VARC-2 major vascular complications
      but not ProGlide use were identified as an independent predictor of one-year
      mortality (adjusted odds ratio 1.54, 95% CI: 1.01-2.34 and 1.01, 95% CI: 0.65
      1.55, respectively). CONCLUSIONS: In this analysis, the use of ProGlide SMCD was
      associated with a reduced risk of vascular and bleeding complications following
      TAVI compared to Prostar SMCD usage. However, major vascular complications but
      not ProGlide use did independently predict long-term mortality.

PMID- 27866141
TI  - Transapical aortic stenting: an initial case series.
AB  - AIMS: The standard approach for thoracic endovascular aortic repair (TEVAR) is
      transfemoral; however, calcifications and tortuosity of the access vessels might
      be so extensive as to increase the operative risk markedly or preclude the
      procedure. This study evaluates the transapical approach as an alternative route
      for TEVAR in such patients. METHODS AND RESULTS: From June 2011 to July 2013, the
      institution's interdisciplinary board for aortic diseases initially denied TEVAR
      for eight patients with thoracic aortic pathology due to extensive calcification
      and tortuosity of the distal vessels. The transapical approach was suggested and
      approved by the board. All procedures were performed in a hybrid operating room
      through a left mini-thoracotomy. The stent grafts were implanted in either the
      proximal descending or the ascending aorta. The deployment was performed under
      rapid ventricular pacing. Procedural success was 100%. There were no
      intraoperative complications. One patient needed re-exploration. There was no 30
      day mortality. In follow-up, one patient suffered type 1B endoleak, which
      required surgery after one year. CONCLUSIONS: The transapical approach for TEVAR
      (TaTEVAR) is a feasible option for patients with distal aorta/iliac vessels
      unsuitable for transfemoral access. It might be even more beneficial for TEVAR of
      the ascending aorta.

PMID- 27866142
TI  - Overstepping anatomical hurdles when opening an extremely rudimentary right
      ventricular outflow tract - greater safety via a hybrid strategy?

PMID- 27866143
TI  - How should I treat renal artery in-stent restenosis and stent fracture after
      endovascular abdominal aortic aneurysm repair?

PMID- 27866144
TI  - Instilling fear makes good business sense: unwarranted hysterectomies in
      Karnataka.
AB  - This paper uses data from two fact-finding exercises in two districts of
      Karnataka to trace how government and private doctors alike pushed women to
      undergo hysterectomies. The doctors provided grossly unscientific information to
      poor Dalit women to instil a fear of "cancer" in their minds to wilfully mislead
      them to undergo hysterectomies, following which many suffered complications and
      died. The paper examines a review, made by two separate panels of experts, of
      women's medical records from private hospitals to illustrate that a large
      proportion of the hysterectomies performed were medically unwarranted; that
      private doctors were using highly suspect diagnostic criteria, based on a single
      ultrasound scan, to perform the hysterectomies and had not sent even a single
      sample for histopathology; and that the medical records were incomplete,
      erroneous and, in several instances, manipulated. The paper describes how a
      combination of patriarchal bias, professional unscrupulousness and pro-private
      healthcare policies posed a serious threat to the survival and well-being of
      women in Karnataka.

PMID- 27866145
TI  - Cosmetic limb lengthening in a patient of normal stature: ethical considerations.
AB  - Recently, a 23-year-old male patient underwent cosmetic limb lengthening, despite
      the fact that his height was that of the average Indian male (5 feet 7 inches).
      The patient's parents and the media criticised the orthopaedic surgeon who had
      performed the surgery for undertaking an unethical operation. This paper
      discusses the relevant clinical evidence, ethical aspects and ethical theories
      surrounding the case. We conclude that the surgeon's decision to perform the
      surgery seems to be fair and appropriate from the ethical and clinical
      perspectives.

PMID- 27866146
TI  - Hearing Preservation After Penetrating Cochlear Injury.
AB  - OBJECTIVES: To share results and recommendations for management of penetrating
      cochlear injury. METHODS: A patient underwent repair of a penetrating cochlear
      injury after a projectile led to a traumatic cochleostomy with a narrow miss of
      the facial nerve and intracranial carotid artery. RESULTS: Postoperatively, the
      patient's audiogram demonstrated a pure tone average of 47.5 dB for air
      conduction and 35 dB for bone conduction, worse in the high frequencies, with a
      Word Recognition Score of 76%. CONCLUSIONS: Hearing loss from a penetrating
      cochlear injury can be mitigated with early repair, minimizing inner ear trauma,
      and steroid use to treat posttraumatic labyrinthitis.

PMID- 27866147
TI  - Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for
      Preventing Progression of Age-Related Macular Degeneration.
AB  - OBJECTIVE: To briefly review age-related macular degeneration (AMD), the main
      findings from the Age Related Eye Disease Study (AREDS) report number 8 on the
      use of nutritional supplements for AMD, and to focus on data suggesting that
      supplement use should be guided using genetic testing of AMD risk genes. DATA
      SOURCES: A literature search (January 2001 through October 26, 2016) was
      conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic
      use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics,
      Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use.
      Bibliographies of publications identified were also reviewed. STUDY SELECTION AND
      DATA EXTRACTION: English-language studies assessing AREDS supplement response in
      patients with AMD in relation to complement factor H gene ( CFH) and age-related
      maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. DATA
      SYNTHESIS: Three of the 4 studies demonstrated a treatment interaction between
      ARMS2 and CFH genotypes and a differential response to supplements. The fourth
      study documented an interaction for the CFH genotype only. Reported response
      interactions included attenuated response, no response, and good response,
      whereas a subset showed increased progression of AMD. Conversely, one study
      reported no interactions between CFH and ARMS2 risk alleles and response to
      supplements. CONCLUSIONS: The weight of the evidence supports using genetic
      testing to guide selection of ocular vitamin use. This approach will avoid using
      supplements that could speed the progression of AMD in vulnerable patients, avoid
      using supplements that will have little to no effect in others, and result in
      appropriately using supplements in those that are likely to derive meaningful
      benefits.

PMID- 27866148
TI  - Identification of Genes Mediating Drosophila Follicle Cell Progenitor
      Differentiation by Screening for Modifiers of GAL4::UAS Variegation.
AB  - The Drosophila melanogaster ovarian follicle cell lineage provides a powerful
      system for investigating how epigenetic changes contribute to differentiation.
      Downstream from an epithelial stem cell, follicle progenitors undergo nine
      mitotic cell cycles before transitioning to the endocycle and initiating
      differentiation. During their proliferative phase, follicle progenitors
      experience Lsd1-dependent changes in epigenetic stability that can be monitored
      using GAL4::UAS variegation. Eventually, follicle progenitors acquire competence
      to respond to Delta, a Notch ligand present in the environment, which signals
      them to cease division and initiate differentiation. The time required to acquire
      competence determines the duration of mitotic cycling and hence the final number
      of follicle cells. We carried out a screen for dominant modifiers of variegation
      spanning nearly 70% of Drosophila euchromatin to identify new genes influencing
      follicle progenitor epigenetic maturation. The eight genes found include
      chromatin modifiers, but also cell cycle regulators and transcription factors.
      Five of the modifier genes accelerate the acquisition of progenitor competence
      and reduce follicle cell number, however, the other three genes affect follicle
      cell number in an unexpected manner.

PMID- 27866149
TI  - Correlations of Genotype with Climate Parameters Suggest Caenorhabditis elegans
      Niche Adaptations.
AB  - Species inhabit a variety of environmental niches, and the adaptation to a
      particular niche is often controlled by genetic factors, including gene-by
      environment interactions. The genes that vary in order to regulate the ability to
      colonize a niche are often difficult to identify, especially in the context of
      complex ecological systems and in experimentally uncontrolled natural
      environments. Quantitative genetic approaches provide an opportunity to
      investigate correlations between genetic factors and environmental parameters
      that might define a niche. Previously, we have shown how a collection of 208
      whole-genome sequenced wild Caenorhabditis elegans can facilitate association
      mapping approaches. To correlate climate parameters with the variation found in
      this collection of wild strains, we used geographic data to exhaustively curate
      daily weather measurements in short-term (3 month), middle-term (one year), and
      long-term (three year) durations surrounding the date of strain isolation. These
      climate parameters were used as quantitative traits in association mapping
      approaches, where we identified 11 quantitative trait loci (QTL) for three
      climatic variables: elevation, relative humidity, and average temperature. We
      then narrowed the genomic interval of interest to identify gene candidates with
      variants potentially underlying phenotypic differences. Additionally, we
      performed two-strain competition assays at high and low temperatures to validate
      a QTL that could underlie adaptation to temperature and found suggestive evidence
      supporting that hypothesis.

PMID- 27866151
TI  - Genotyping-by-Sequencing-Based Investigation of the Genetic Architecture
      Responsible for a ~Sevenfold Increase in Soybean Seed Stearic Acid.
AB  - Soybean oil is highly unsaturated but oxidatively unstable, rendering it nonideal
      for food applications. Until recently, the majority of soybean oil underwent
      partial chemical hydrogenation, which produces trans fats as an unavoidable
      consequence. Dietary intake of trans fats and most saturated fats are
      conclusively linked to negative impacts on cholesterol levels and cardiovascular
      health. Two major soybean oil breeding targets are: (1) to reduce or eliminate
      the need for chemical hydrogenation, and (2) to replace the functional properties
      of partially hydrogenated soybean oil. One potential solution is the elevation of
      seed stearic acid, a saturated fat which has no negative impacts on
      cardiovascular health, from 3 to 4% in typical cultivars to > 20% of the seed
      oil. We performed QTL analysis of a population developed by crossing two mutant
      lines, one with a missense mutation affecting a stearoyl-acyl-carrier protein
      desaturase gene resulting in ~11% seed stearic acid crossed to another mutant,
      A6, which has 24-28% seed stearic acid. Genotyping-by-sequencing (GBS)-based QTL
      mapping identified 21 minor and major effect QTL for six seed oil related traits
      and plant height. The inheritance of a large genomic deletion affecting
      chromosome 14 is the basis for largest effect QTL, resulting in ~18% seed stearic
      acid. This deletion contains SACPD-C and another gene(s); loss of both genes
      boosts seed stearic acid levels to >= 18%. Unfortunately, this genomic deletion
      has been shown in previous studies to be inextricably correlated with reduced
      seed yield. Our results will help inform and guide ongoing breeding efforts to
      improve soybean oil oxidative stability.

PMID- 27866150
TI  - CRISPR/Cas9-Induced Double-Strand Break Repair in Arabidopsis Nonhomologous End
      Joining Mutants.
AB  - Double-strand breaks (DSBs) are one of the most harmful DNA lesions. Cells
      utilize two main pathways for DSB repair: homologous recombination (HR) and
      nonhomologous end-joining (NHEJ). NHEJ can be subdivided into the KU-dependent
      classical NHEJ (c-NHEJ) and the more error-prone KU-independent backup-NHEJ (b
      NHEJ) pathways, involving the poly (ADP-ribose) polymerases (PARPs). However, in
      the absence of these factors, cells still seem able to adequately maintain genome
      integrity, suggesting the presence of other b-NHEJ repair factors or pathways
      independent from KU and PARPs. The outcome of DSB repair by NHEJ pathways can be
      investigated by using artificial sequence-specific nucleases such as CRISPR/Cas9
      to induce DSBs at a target of interest. Here, we used CRISPR/Cas9 for DSB
      induction at the Arabidopsis cruciferin 3 (CRU3) and protoporphyrinogen oxidase
      (PPO) genes. DSB repair outcomes via NHEJ were analyzed using footprint analysis
      in wild-type plants and plants deficient in key factors of c-NHEJ (ku80), b-NHEJ
      (parp1 parp2), or both (ku80 parp1 parp2). We found that larger deletions of >20
      bp predominated after DSB repair in ku80 and ku80 parp1 parp2 mutants,
      corroborating with a role of KU in preventing DSB end resection. Deletion lengths
      did not significantly differ between ku80 and ku80 parp1 parp2 mutants,
      suggesting that a KU- and PARP-independent b-NHEJ mechanism becomes active in
      these mutants. Furthermore, microhomologies and templated insertions were
      observed at the repair junctions in the wild type and all mutants. Since these
      characteristics are hallmarks of polymerase theta-mediated DSB repair, we suggest
      a possible role for this recently discovered polymerase in DSB repair in plants.

PMID- 27866153
TI  - Exploring Personality and Readiness to Change in Patients With Substance Use
      Disorders With and Without ADHD.
AB  - OBJECTIVE: To explore personality and readiness to change among substance use
      disorders (SUD) patients with and without ADHD. METHOD: SUD + ADHD versus SUD -
      ADHD patients consecutively entering treatment between 2010 and 2012 were
      compared concerning personality (Temperament and Character Inventory) and
      readiness to change (Stages of Change Readiness and Treatment Eagerness Scale).
      RESULTS: Among 103 SUD patients (76 men, age M = 43.3, SD = 11.1), 16 (15.5%)
      were diagnosed with ADHD. SUD + ADHD patients reported significantly elevated
      eagerness to effort ( p = .008) compared with SUD - ADHD patients, who reported
      significantly elevated fear of uncertainty ( p < .000). SUD + ADHD patients
      reported higher ambition ( p = .025), self-forgetfulness ( p = .029), and lower
      recognition ( p = .022). They were younger ( p = .019) and showed more often
      amphetamine addiction ( p = .022) compared with SUD - ADHD patients. CONCLUSION:
      The distinct characteristics found in SUD + ADHD and SUD - ADHD patients
      underline the need for differentiated treatment interventions.

PMID- 27866152
TI  - The Effect of Childhood ADD/ADHD on Parental Workforce Participation.
AB  - OBJECTIVE: This research aimed to examine the impact of attention deficit
      disorder (ADD)/ADHD in children on parental labor force participation across
      different child age groups. METHOD: This study utilized a longitudinal,
      quantitative analyses approach. All data were collected from Wave 6 of the
      Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC)
      survey. RESULTS: After adjusting for various confounders, mothers whose children
      were 10/11 years old and had been diagnosed with ADD/ADHD were significantly more
      likely to be out of the labor force compared with those mothers whose child had
      not been diagnosed with ADD/ADHD. The impact was more pronounced for single
      mothers. No significant influence on paternal labor force participation was
      found. CONCLUSION: In assessing the cost-effectiveness of interventions for
      ADD/ADHD, policy makers and researchers must consider the long-term social and
      economic effects of ADD/ADHD on maternal workforce participation when considering
      costs and outcomes.

PMID- 27866154
TI  - The Correlation Between Cognitive and Movement Shifting and Brain Activity in
      Children With ADHD.
AB  - OBJECTIVE: We assessed the correlation between the deficits of cognition,
      movement, and brain activity in children with Attention Deficit Hyperactvity
      Disorder (ADHD). METHOD: We recruited 15 children with ADHD and 15 age- and sex
      matched healthy control participants. Clinical symptoms, cognitive shifting,
      movement shifting, and brain activity were assessed using the Korean ADHD Rating
      Scale, the Wisconsin Card Sorting Test (WCST), the 7- and 14-ring drill test with
      hop jumps (7 HJ and 14 HJ), and 3.0 Tesla functional magnetic resonance imaging
      scanner, respectively. RESULTS: ADHD children showed an increased distance
      traveled and decreased speed on the 14 HJ task. In response to the WCST task,
      ADHD children showed decreased activation within right gyrus. Total distance on
      the 14 HJ task was negatively correlated with the mean beta value of Cluster 2 in
      ADHD children. CONCLUSION: These results suggested that children with ADHD showed
      difficulty with attention shifting as well as with movement shifting.

PMID- 27866155
TI  - The Assessment of the Relationship Between ADHD and Posttraumatic Stress Disorder
      in Child and Adolescent Patients.
AB  - OBJECTIVE: This study examined ADHD comorbidity in child and adolescent patients
      who diagnosed with posttraumatic stress disorder (PTSD) or obsessive compulsive
      disorder (OCD). METHOD: Sixty-eight child and adolescent patients with PTSD and
      42 child and adolescent patients with OCD were evaluated for ADHD. The sample
      included 110 patients who were administered structured clinical interviews based
      on the Diagnostic and Statistical Manual of Mental Disorders (5th ed.). RESULTS:
      Results showed that 22.05% patients with PTSD and 59.52% patients with OCD met
      criteria for ADHD. CONCLUSION: The results of our study indicate that no
      meaningful differences were detected in comparisons between PTSD and OCD groups,
      in having ADHD as comorbidity.

PMID- 27866156
TI  - Hide-and-seek: the interplay between cancer stem cells and the immune system.
AB  - The enhanced ability of cancer stem cells (CSCs) to give rise to new tumors
      suggests that these cells may also have an advantage in evading immune detection
      and elimination. This tumor-forming ability, combined with the known plasticity
      of the immune system, which can play both protumorigenic and antitumorigenic
      roles, has motivated investigations into the interaction between CSCs and the
      immune system. Herein, we review the interplay between host immunity and CSCs by
      examining the immune-related mechanisms that favor CSCs and the CSC-mediated
      expansion of protumorigenic immune cells. Furthermore, we discuss immune cells,
      such as natural killer cells, that preferentially target CSCs and the strategies
      used by CSCs to evade immune detection and destruction. An increased
      understanding of these interactions and the pathways that regulate them may allow
      us to harness immune system components to create new adjuvant therapies that
      eradicate CSCs and improve patient survival.

PMID- 27866157
TI  - Loss of free fatty acid receptor 2 enhances colonic adenoma development and
      reduces the chemopreventive effects of black raspberries in ApcMin/+ mice.
AB  - We previously showed that black raspberries (BRBs) have beneficial effects in
      human colorectal cancer and a mouse model of colorectal cancer (ApcMin/+). The
      current study investigated the role of free fatty acid receptor 2 (FFAR2) in
      colon carcinogenesis and whether the FFAR2 signaling pathway contributes to BRB
      mediated chemoprevention in mice. FFAR2 (also named GPR43) is a member of the G
      protein-coupled receptor family that is expressed in leukocytes and colon.
      ApcMin/+ and ApcMin/+-FFAR2-/- mice were given a control diet or the control diet
      supplemented with 5% BRBs for 8 weeks. FFAR2 deficiency promoted colonic polyp
      development, with 100% incidence and increased polyp number and size. The
      ApcMin/+ mice developed colonic tubular adenoma, whereas the ApcMin/+-FFAR2-/-
      mice developed colonic tubular adenoma with high-grade dysplasia. FFAR2
      deficiency also enhanced the cAMP-PKA-CREB-HDAC pathway, downstream of FFAR2
      signaling, and increased activation of the Wnt pathway, and raised the percentage
      of GR-1+ neutrophils in colonic lamina propria (LP) and increased infiltration of
      GR-1+ neutrophils into colonic polyps. BRBs suppressed colonic polyp development
      and inhibited the cAMP-PKA-CREB-HDAC and Wnt pathways in the ApcMin/+ mice but
      not the ApcMin/+-FFAR2-/- mice. They also increased the percentage of GR-1+
      neutrophils and cytokine secretion in colonic LP and decreased the infiltration
      of GR-1+ neutrophils and IL-1beta expression in colon polyps of ApcMin/+ mice but
      not ApcMin/+-FFAR2-/- mice. These results suggest that loss of FFAR2 drives colon
      tumorigenesis and that BRBs require functional FFAR2 to be chemopreventive. BRBs
      have the potential to modulate the host immune system, thereby enhancing the
      antitumor immune microenvironment.

PMID- 27866161
TI  - Self-Administered Assessment of Health Literacy in Adolescents Using the Newest
      Vital Sign.
AB  - The "Newest Vital Sign" (NVS) is a validated health literacy assessment tool
      typically administered by clinicians. The objective of this study was to assess
      if the NVS could be self-administered in adolescents to measure health literacy.
      Sixth graders in a Colorado middle school were provided a self-administered
      survey containing the NVS, a section for parent permission, and a section for the
      student's age, gender, grade, and previous elementary school. In all, 167 sixth
      graders returned usable surveys (45% return rate), and the average health
      literacy score was 3.75 +/- 1.70. Almost two thirds (62.9%) of the students
      scored in the adequate health literacy range, while only 12.6% scored in the
      limited health literacy range. Health literacy scores were similar when evaluated
      based on gender. However, when students were grouped based on prior elementary
      school attendance, students who matriculated from one elementary school had an
      average NVS score significantly lower than two other elementary schools (p < .001
      and p < .05). Self-administration of the NVS was successful and showed similar
      health literacy scores compared to other studies in adolescents. Using the NVS as
      a self-administered tool could greatly increase its function as a quick health
      literacy assessment for adolescents, both in clinical practice and in school
      based health education.

PMID- 27866160
TI  - Utilizing Talking Circles as a Means of Gathering American Indian Stories for
      Developing a Nutrition and Physical Activity Curriculum.
AB  - This qualitative study used a focus group approach (talking circles) to elicit
      tribal elder insight on important concepts for the purpose of creating a
      curriculum to teach tribal youth in South Dakota about nutrition and physical
      activity in culturally appropriate ways. The focus groups were part of a larger
      project that is exploring mechanisms for creating culturally relevant nutrition
      and physical activity education for American Indian youth. A series of "Eat
      Smart, Play Hard" posters, created by South Dakota State University Extension,
      served as the starting point for talking circle conversations with tribal elders
      about teaching nutrition and physical activity to children. Data from the talking
      circles were analyzed using qualitative content analysis for themes in elder
      dialogs. In open-ended conversations, elders discussed barriers and success in
      achieving good nutrition and physical activity, important aspects of the Siouan
      food culture, and historical relationships with food. They shared insights on
      food ingredients and methods of obtaining and preparing food that were and are
      currently important to their communities. These data were used to better
      understand the Native cultural perspectives on nutrition and physical activity
      and to create effective educational material for Native youth that could be used
      to teach them in culturally relevant ways.

PMID- 27866158
TI  - A Nitric Oxide Storage and Transport System That Protects Activated Macrophages
      from Endogenous Nitric Oxide Cytotoxicity.
AB  - Nitric oxide (NO) is integral to macrophage cytotoxicity against tumors due to
      its ability to induce iron release from cancer cells. However, the mechanism for
      how activated macrophages protect themselves from endogenous NO remains unknown.
      We previously demonstrated by using tumor cells that glutathione S-transferase P1
      (GSTP1) sequesters NO as dinitrosyl-dithiol iron complexes (DNICs) and inhibits
      NO-mediated iron release from cells via the transporter multidrug resistance
      protein 1 (MRP1/ABCC1). These prior studies also showed that MRP1 and GSTP1
      protect tumor cells against NO cytotoxicity, which parallels their roles in
      defending cancer cells from cytotoxic drugs. Considering this, and because GSTP1
      and MRP1 are up-regulated during macrophage activation, this investigation
      examined whether this NO storage/transport system protects macrophages against
      endogenous NO cytotoxicity in two well characterized macrophage cell types (J774
      and RAW 264.7). MRP1 expression markedly increased upon macrophage activation,
      and the role of MRP1 in NO-induced 59Fe release was demonstrated by Mrp1 siRNA
      and the MRP1 inhibitor, MK571, which inhibited NO-mediated iron efflux.
      Furthermore, Mrp1 silencing increased DNIC accumulation in macrophages,
      indicating a role for MRP1 in transporting DNICs out of cells. In addition,
      macrophage 59Fe release was enhanced by silencing Gstp1, suggesting GSTP1 was
      responsible for DNIC binding/storage. Viability studies demonstrated that GSTP1
      and MRP1 protect activated macrophages from NO cytotoxicity. This was confirmed
      by silencing nuclear factor-erythroid 2-related factor 2 (Nrf2), which decreased
      MRP1 and GSTP1 expression, concomitant with reduced 59Fe release and macrophage
      survival. Together, these results demonstrate a mechanism by which macrophages
      protect themselves against NO cytotoxicity.

PMID- 27866159
TI  - Pairing Animal Cartoon Characters With Produce Stimulates Selection Among Child
      Zoo Visitors.
AB  - In order to address the pervasive trend of underconsumption of fruits and
      vegetables among children, we examined the hypothesis that children would be more
      likely to select fruits (apple slices, bananas, and oranges) and vegetables (baby
      carrots) when paired with animal cartoon image than when available without the
      character image. Tested in a randomized experiment using counterbalancing,
      products were arranged on two tables at two separate family fun nights held at a
      local zoo. Animal character produce parings were manipulated by placing one of
      two animals (tamarin or iguana) next to two of the four fruit or vegetable
      selections at each table, and by changing when available without the image. In
      total, 755 produce selections were made. Significantly more products paired with
      a character were selected (62.38%) than the same products, not paired (37.62%),
      chi2 = 46.32, df = 1, p < .001. The odds ratio of the treatment versus control
      was 1.66 (i.e., 471/284), indicating that children were 66% more likely to select
      a snack when paired with an animal cartoon. Study findings highlight the positive
      impact of animal cartoons on children's fruit and vegetable snack selections, and
      results suggest the potential for using animal cartoons to encourage fruit and
      vegetable selection for children.

PMID- 27866162
TI  - Outcomes Associated With Familial Versus Nonfamilial Atrial Fibrillation: A
      Matched Nationwide Cohort Study.
AB  - BACKGROUND: We examined all-cause mortality and long-term thromboembolic risk
      (ischemic stroke, transient ischemic attack, systemic thromboembolism) in
      patients with and without familial atrial fibrillation (AF). METHODS AND RESULTS:
      Using Danish nationwide registry data, we identified all patients diagnosed with
      AF (1995-2012) and divided them into those with familial AF (having a first
      degree family member with a prior AF admission) and those with nonfamilial AF. We
      paired those with and without familial AF according to age, year of AF diagnosis,
      and sex in a 1:1 match. Using cumulative incidence and multivariable Cox models,
      we examined the risk of long-term outcomes. We identified 8658 AF patients (4329
      matched pairs) with and without familial AF. The median age was 50 years
      (interquartile range 43-54 years), and 21.4% were women. Compared with
      nonfamilial AF patients, those with familial AF had slightly less comorbid
      illness but similar overall CHA2DS2-VASc score (P=0.155). Median follow-up was
      3.4 years (interquartile range 1.5-6.5 years). Patients with familial AF had risk
      of death and thromboembolism similar to those with nonfamilial AF (adjusted
      hazard ratio 0.91 [95% CI 0.79-1.04] for death and 0.90 [95% CI 0.71-1.14] for
      thromboembolism). CONCLUSIONS: Although family history of AF is associated with
      increased likelihood for development of AF, once AF developed, long-term risks of
      death and thromboembolic complications were similar in familial and nonfamilial
      AF patients.

PMID- 27866163
TI  - Prognosis in Familial Atrial Fibrillation.

PMID- 27866165
TI  - Anemia and Acute Coronary Syndrome: Time for Intervention Studies.

PMID- 27866164
TI  - Relationship Between Anemia and Mortality Outcomes in a National Acute Coronary
      Syndrome Cohort: Insights From the UK Myocardial Ischemia National Audit Project
      Registry.
AB  - BACKGROUND: We aim to determine the prevalence of anemia in acute coronary
      syndrome (ACS) patients and compare their clinical characteristics, management,
      and clinical outcomes to those without anemia in an unselected national ACS
      cohort. METHODS AND RESULTS: The Myocardial Ischemia National Audit Project
      (MINAP) registry collects data on all adults admitted to hospital trusts in
      England and Wales with diagnosis of an ACS. We conducted a retrospective cohort
      study by analyzing patients in this registry between January 2006 and December
      2010 and followed them up until August 2011. Multiple logistic regressions were
      used to determine factors associated with anemia and the adjusted odds of 30-day
      mortality with 1 g/dL incremental hemoglobin increase and the 30-day and 1-year
      mortality for anemic compared to nonanemic groups. Analyses were adjusted for
      covariates. Our analysis of 422 855 patients with ACS showed that 27.7% of
      patients presenting with ACS are anemic and that these patients are older, have a
      greater prevalence of renal disease, peripheral vascular disease, diabetes
      mellitus, and previous acute myocardial infarction, and are less likely to
      receive evidence-based therapies shown to improve clinical outcomes. Finally, our
      analysis suggests that anemia is independently associated with 30-day (OR 1.28,
      95% CI 1.22-1.35) and 1-year mortality (OR 1.31, 95% CI 1.27-1.35), and we
      observed a reverse J-shaped relationship between hemoglobin levels and mortality
      outcomes. CONCLUSIONS: The prevalence of anemia in a contemporary national ACS
      cohort is clinically significant. Patients with anemia are older and multimorbid
      and less likely to receive evidence-based therapies shown to improve clinical
      outcomes, with the presence of anemia independently associated with mortality
      outcomes.

PMID- 27866166
TI  - Variability in a Short Tandem Repeat Mediates Complex Epistatic Interactions in
      Arabidopsis thaliana.
AB  - Short tandem repeats (STRs) are hypervariable genetic elements that occur
      frequently in coding regions. Their high mutation rate readily generates genetic
      variation, contributing to adaptive evolution and human diseases. We previously
      reported that natural ELF3 polyglutamine variants cause reciprocal genetic
      incompatibilities in two divergent Arabidopsis thaliana backgrounds. Here, we
      dissect the genetic architecture of this incompatibility, revealing as many as
      four loci putatively interacting with ELF3 We were able to specifically identify
      one such ELF3-interacting gene, LSH9 We further used a yeast two-hybrid strategy
      to identify proteins whose physical interactions with ELF3 were affected by
      polyglutamine tract length. We found two proteins for which this was the case,
      ELF4 and AtGLDP1. Using these two approaches, we identify specific genetic
      interactions and physical mechanisms by which the ELF3 polyglutamine tract may
      mediate the observed genetic incompatibilities. Our work elucidates how STR
      variation, which is generally underascertained in population-scale sequencing,
      can contribute to phenotypic variation. Furthermore, our results support our
      proposal that highly variable STR loci can contribute to the epistatic component
      of heritability.

PMID- 27866168
TI  - Fixation Probability in a Haploid-Diploid Population.
AB  - Classical population genetic theory generally assumes either a fully haploid or
      fully diploid life cycle. However, many organisms exhibit more complex life
      cycles, with both free-living haploid and diploid stages. Here we ask what the
      probability of fixation is for selected alleles in organisms with haploid-diploid
      life cycles. We develop a genetic model that considers the population dynamics
      using both the Moran model and Wright-Fisher model. Applying a branching process
      approximation, we obtain an accurate fixation probability assuming that the
      population is large and the net effect of the mutation is beneficial. We also
      find the diffusion approximation for the fixation probability, which is accurate
      even in small populations and for deleterious alleles, as long as selection is
      weak. These fixation probabilities from branching process and diffusion
      approximations are similar when selection is weak for beneficial mutations that
      are not fully recessive. In many cases, particularly when one phase predominates,
      the fixation probability differs substantially for haploid-diploid organisms
      compared to either fully haploid or diploid species.

PMID- 27866169
TI  - A New Mechanism for Mendelian Dominance in Regulatory Genetic Pathways:
      Competitive Binding by Transcription Factors.
AB  - We report a new mechanism for allelic dominance in regulatory genetic
      interactions that we call binding dominance. We investigated a biophysical model
      of gene regulation, where the fractional occupancy of a transcription factor (TF)
      on the cis-regulated promoter site it binds to is determined by binding energy (
      DeltaG) and TF dosage. Transcription and gene expression proceed when the TF is
      bound to the promoter. In diploids, individuals may be heterozygous at the cis
      site, at the TF's coding region, or at the TF's own promoter, which determines
      allele-specific dosage. We find that when the TF's coding region is heterozygous,
      TF alleles compete for occupancy at the cis-sites and the tighter-binding TF is
      dominant in proportion to the difference in binding strength. When the TF's own
      promoter is heterozygous, the TF produced at the higher dosage is also dominant.
      Cis-site heterozygotes have additive expression and therefore codominant
      phenotypes. Binding dominance propagates to affect the expression of downstream
      loci and it is sensitive in both magnitude and direction to genetic background,
      but its detectability often attenuates. While binding dominance is inevitable at
      the molecular level, it is difficult to detect in the phenotype under some
      biophysical conditions, more so when TF dosage is high and allele-specific
      binding affinities are similar. A body of empirical research on the biophysics of
      TF binding demonstrates the plausibility of this mechanism of dominance, but
      studies of gene expression under competitive binding in heterozygotes in a
      diversity of genetic backgrounds are needed.

PMID- 27866170
TI  - Measurement Invariance of a Body Dysmorphic Disorder Symptom Questionnaire Across
      Sex: The Body Image Questionnaire-Child and Adolescent Version.
AB  - Measures of body dysmorphic disorder symptoms have received little psychometric
      evaluation in adolescent samples. This study aimed to examine cross-sex
      measurement invariance in the Body Image Questionnaire-Child and Adolescent
      version (BIQ-C) to establish whether observed sex differences in total scores may
      be meaningful or due to differences in measurement properties. A sample of 3,057
      Australian high school students completed the initial screening item of the
      measure (63.2% male, Mage = 14.58 years, SD = 1.37, range = 12-18 years). Of
      these participants, 1,512 (49.5%) reported appearance concerns and thus completed
      the full measure. Partial scalar measurement invariance was established among a
      revised two-factor, 9-item version of the BIQ-C (BIQ-C-9). Females reported
      significantly greater latent factor variance, higher BIQ-C-9 total and factor
      scores, and higher scores on most individual BIQ-C-9 items. The measure can be
      used with caution to compare body dysmorphic disorder symptoms between male and
      female adolescents, though sex-specific cutoff scores should be used.

PMID- 27866167
TI  - Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen
      Cryptococcus neoformans.
AB  - Thermotolerance is a crucial virulence attribute for human pathogens, including
      the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss
      of the protein kinase Sch9 increases C. neoformans thermotolerance, but its
      regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent
      and Sch9-independent signaling networks modulating C. neoformans thermotolerance
      by using genome-wide transcriptome analysis and reverse genetic approaches.
      During temperature upshift, genes encoding for molecular chaperones and heat
      shock proteins were upregulated, whereas those for translation, transcription,
      and sterol biosynthesis were highly suppressed. In this process, Sch9 regulated
      basal expression levels or induced/repressed expression levels of some
      temperature-responsive genes, including heat shock transcription factor (HSF1)
      and heat shock proteins (HSP104 and SSA1). Notably, we found that the HSF1
      transcript abundance decreased but the Hsf1 protein became transiently
      phosphorylated during temperature upshift. Nevertheless, Hsf1 is essential for
      growth and its overexpression promoted C. neoformans thermotolerance.
      Transcriptome analysis using an HSF1 overexpressing strain revealed a dual role
      of Hsf1 in the oxidative stress response and thermotolerance. Chromatin
      immunoprecipitation demonstrated that Hsf1 binds to the step-type like heat shock
      element (HSE) of its target genes more efficiently than to the perfect- or gap
      type HSE. This study provides insight into the thermotolerance of C. neoformans
      by elucidating the regulatory mechanisms of Sch9 and Hsf1 through the genome
      scale identification of temperature-dependent genes.

PMID- 27866172
TI  - What Does the WRAML2 Core Battery Measure? Utilizing Exploratory and Confirmatory
      Techniques to Disclose Higher Order Structure.
AB  - The present study examined the factor structure of the Wide Range Assessment of
      Memory and Learning-Second Edition (WRAML2) core battery with participants from
      the normative sample aged 9 to 90 years ( n = 880) using higher order exploratory
      and confirmatory factor analytic techniques that were not reported in the in the
      WRAML2 Administration and Technical Manual. Exploratory factor analysis results
      suggested only one factor, whereas confirmatory factor analysis results favored
      the three factors posited by the test authors. Although model fit statistics were
      equivalent for the oblique, indirect hierarchical, and direct hierarchical
      measurement models, it was determined that the bifactor model best disclosed the
      influence of latent dimensions on WRAML2 manifest variables. In the three-factor
      bifactor model, the general factor accounted for 31% of the total variance and
      69% of the common variance, whereas the three first-order factors combined
      accounted for 41% of the total variance and 31% of the common variance. Latent
      factor reliability coefficients (as estimated by omegah) indicated that only the
      general factor was measured with enough precision to warrant confident clinical
      interpretation. Implications for clinical interpretation of WRAML2 scores and the
      procedures utilized in the development of related measures are discussed.

PMID- 27866171
TI  - Refining Diagnostic Procedures for Adults With Symptoms of ADHD.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a chronic disorder that
      afflicts individuals into adulthood. The field continues to refine diagnostic
      standards for ADHD in adults, complicated by the disorder's heterogeneous
      presentation, subjective symptoms, and overlap with other disorders. Two key
      diagnostic questions are from whom to collect diagnostic information and which
      symptoms should be contained on an adult diagnostic checklist. Using a trifactor
      model, Martel et al. examine these questions in a sample of adults with and
      without self-identified ADHD symptoms. In this response, we highlight the
      importance of their finding that self and informant symptom reports differ in a
      sample of adults who acknowledge ADHD symptoms. We also review issues that
      continue to face the field related to model specification, evaluating symptom
      utility, and sample composition, discussing how these issues influence
      conclusions that may be drawn from Martel et al. and similar investigations. We
      conclude that the article makes an important research contribution about the
      nature of self and informant ADHD symptom reports but emphasize that symptom
      checklist refinement must occur through a broad lens that considers work from a
      range of sample types and clinically informative analytic strategies.

PMID- 27866174
TI  - Sample size calculation based on generalized linear models for differential
      expression analysis in RNA-seq data.
AB  - As RNA-seq rapidly develops and costs continually decrease, the quantity and
      frequency of samples being sequenced will grow exponentially. With proteomic
      investigations becoming more multivariate and quantitative, determining a study's
      optimal sample size is now a vital step in experimental design. Current methods
      for calculating a study's required sample size are mostly based on the hypothesis
      testing framework, which assumes each gene count can be modeled through Poisson
      or negative binomial distributions; however, these methods are limited when it
      comes to accommodating covariates. To address this limitation, we propose an
      estimating procedure based on the generalized linear model. This easy-to-use
      method constructs a representative exemplary dataset and estimates the
      conditional power, all without requiring complicated mathematical approximations
      or formulas. Even more attractive, the downstream analysis can be performed with
      current R/Bioconductor packages. To demonstrate the practicability and efficiency
      of this method, we apply it to three real-world studies, and introduce our on
      line calculator developed to determine the optimal sample size for a RNA-seq
      study.

PMID- 27866173
TI  - A rapid UPLC-MS/MS assay for the simultaneous measurement of fluconazole,
      voriconazole, posaconazole, itraconazole, and hydroxyitraconazole concentrations
      in serum.
AB  - BACKGROUND: Triazole antifungals are essential to the treatment and prophylaxis
      of fungal infections. Significant pharmacokinetic variability combined with a
      clinical need for faster turnaround times has increased demand for in-house
      therapeutic drug monitoring of these drugs, which is best performed using mass
      spectrometry-based platforms. However, technical and logistical obstacles to
      implementing these platforms in hospital laboratories have limited their
      widespread utilization. Here, we present the development and validation of a fast
      and simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC
      MS/MS) method to measure fluconazole, voriconazole, posaconazole, itraconazole,
      and hydroxyitraconazole in human serum suitable for incorporation into a hospital
      clinical laboratory. METHODS: Serum samples (20 uL) were prepared using protein
      precipitation in the presence of deuterated internal standards. Chromatographic
      separation was accomplished using reversed phase UPLC and analysis was performed
      using positive-mode electrospray ionization and collision-induced dissociation
      MS. RESULTS: Total analytical run time was 3 min. All analytes demonstrated
      linearity (r2>0.998) from 0.1 to 10 ug/mL (1-100 ug/mL for fluconazole),
      acceptable accuracy and precision (%DEV<15% and %CV<15% at all levels tested),
      suitable stability under relevant storage conditions, and correlated well with
      reference laboratory results. CONCLUSIONS: A simple and rapid UPLC-MS/MS method
      for monitoring multiple triazole antifungals was developed with a focus on the
      needs of hospital laboratories. The assay is suitable for clinical utilization
      and management of patients on these medications.

PMID- 27866175
TI  - Association Between Diabetes-related Knowledge and Medication Adherence: Results
      From Cross-sectional Analysis.
AB  - Context * Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide.
      To have optimal glycemic control, T2DM patients must have sufficient diabetes
      related knowledge and must adhere positively and closely to a prescribed regimen.
      Medication adherence is a key determinant of therapeutic success in patients with
      T2DM. However, adherence to medications among T2DM patients varies widely, with
      estimates ranging from 36%-94%. Objective * The purpose of the study was to
      assess the level of and the association between diabetes-related knowledge and
      medication adherence among T2DM patients in Pakistan. Design * The research team
      conducted a cross-sectional survey. Setting * The study was carried out at the
      outpatient clinic of a public-sector teaching hospital in Sargodha, Pakistan.
      Participants * Participants were 392 diabetic patients of the hospital. Outcome
      Measures * In addition to the collection of data on the demographic and disease
      related characteristics of the participants, the Urdu versions of the Morisky
      Medication Adherence Scale (MMAS-U) and the Michigan Diabetes Knowledge Test
      (MDKT-U) were used to assess medication adherence and diabetes-related knowledge,
      respectively. Descriptive statistics were used to determine the demographic and
      disease characteristics, whereas a Spearman rank correlation was used to measure
      the association between medication adherence and diabetes-related knowledge.
      Results * The mean age of the participants was 50.77 +/- 9.671 y, with males
      being the dominant gender (n = 222, 56.6%). The mean duration of diabetes was
      5.58 +/- 4.09 y. Of the 392 patients, 245 (62.5%) had an average knowledge of
      diabetes. Furthermore, 282 (71.9%) were categorized as showing poor adherence. A
      significant but weak positive correlation between diabetes-related knowledge and
      medication adherence was found for the study (r = 0.036, P < .05). Conclusions *
      Although diabetes-related knowledge among the patients was average, the adherence
      to treatment was poor. Because patients' knowledge about diabetes was positively
      associated with medication adherence, the research team believes that educating
      patients about the disease and medication management can result in better control
      of T2DM.

PMID- 27866176
TI  - Hypoglycemia Alert Dogs: A Novel, Cost-effective Approach for Diabetes
      Monitoring?
AB  - The recent publication of the results of 3 small trials, and as many as 5 case
      reports on dogs producing clear and intelligible alerts in the presence of their
      owners' hypoglycemia, opens an intriguing clinical scenario for management of
      diabetes. The skill seems attributable to the ability of dogs to identify
      patterns in skin and breath odors as well as to understand and interpret visual
      cues from humans during hypoglycemia. Provided that further trials can confirm
      the findings, the use of diabetes alert dogs that are trained to detect the onset
      of hypoglycemia can be regarded as a fast, versatile, reliable, and cost
      effective approach for safeguarding the health of individuals with diabetes.

PMID- 27866177
TI  - Cranberries for Preventing Recurrent Urinary Tract Infections in Uncircumcised
      Boys.
AB  - Background * Highly concentrated cranberry juice has long been considered to have
      protective properties against urinary tract infections (UTIs), on the basis of
      its content of cranberry proanthocyanidins, with A-type interflavan bonds.
      Objective * This study intended to evaluate the benefits of a highly concentrated
      cranberry juice for the prevention of repeated episodes of UTI in uncircumcised
      boys. Design * The study was a randomized, controlled trial. Setting * The study
      took place at Taipei City Hospital, Renai and Zhongxing Branches (Taipei City,
      Taiwan). Participants * Participants were 55 uncircumcised boys and 12
      circumcised boys, aged 6 to 18 y, with histories of uncomplicated UTI, who were
      patients at the hospital. Intervention * The uncircumcised boys were randomly
      divided into 2 groups: (1) group 1 (n = 28) took 4 oz (120 mL) daily of cranberry
      juice for 6 mo; and (2) group 2 (n = 27), the negative control group, drank a
      placebo juice for 6 months. The circumcised boys in group 3, a positive control
      group, also drank a placebo juice for 6 mo. Outcome Measures * The time to UTI
      (ie, to the appearance of symptoms plus pyuria) was the main outcome.
      Asymptomatic bacteriuria, adherence to the treatment, and adverse effects were
      assessed at monthly visits. Results * After 6 mo of a prophylactic treatment with
      cranberry juice, the incidence of bacteriuria, mainly Escherichia coli, as shown
      in urine cultures at >=1 * 105, were 25% (7/28), 37% (10/27), and 33.3% (4/12) in
      groups 1, 2 and 3, respectively. The comparisons of the rate of prevention of a
      recurrence of UTI between group 1 and group 2 and between group 1 and group 3
      showed that group 1 had fewer recurrent episodes of UTI. No children withdrew
      from the study. No adverse events or side effects were recorded. Conclusions *
      Cranberry juice may reduce the number of repeated episodes of UTI in
      uncircumcised boys and may have beneficial effects against the growth of Gram
      negative bacterial pathogens. Its preventive benefits against UTI in the
      uncircumcised boys were even higher than those of circumcision for the
      circumcised boys.

PMID- 27866178
TI  - Low-level Laser Therapy: A Review of Its Applications in the Management of Oral
      Mucosal Disorders.
AB  - Due to its analgesic, anti-inflammatory, and biostimulating effects, low-level
      laser therapy (LLLT) has been widely used for oral disorders, such as oral lichen
      planus (OLP), xerostomia, recurrent aphthous stomatitis (RAS), herpes labialis,
      burning mouth syndrome (BMS), and oral mucositis (OM). The research team for the
      present study has reviewed the literature on the subject, with an emphasis on the
      applicability of LLLT in general and of its various clinical protocols for the
      management of those oral disorders. In lesions such as the ones occurring in OM,
      RAS, herpes labialis, and OLP, the course of wound healing and the pain have been
      shown to decrease, with a few, or most often, no adverse side effects. The
      literature shows that LLLT can also be effective in reducing symptoms in patients
      with BMS. For the treatment of hyposalivation and xerostomia, the use of LLLT has
      been described in the literature, but no consensus has resulted. Very few
      controlled clinical studies with well-established therapeutic protocols have
      occurred, except for OM, for which LLLT has been widely researched. Although
      information on the use of the laser for some lesions has already been
      consolidated, further research is needed, especially randomized, controlled
      clinical trials with long-term follow-up. Those studies will allow the safe use
      of LLLT, permitting the creation of care protocols for the management of oral
      disorders.

PMID- 27866179
TI  - Tripterygium Glycosides for Treating Late-onset Rheumatoid Arthritis: A
      Systematic Review and Meta-analysis.
AB  - Context * Older- or late-onset rheumatoid arthritis (LORA) is defined as
      rheumatoid arthritis (RA) with an onset of symptoms at age 60 y or older, which
      includes a specific clinical course and features. To date, a specific therapeutic
      treatment for LORA is still a dilemma in modern medicine. Objective * The study
      aimed to assess the effectiveness and safety of Tripterygium glycosides for
      treating LORA. Design * Seven databases were searched from their inceptions until
      June 2015. The research team included randomized, controlled trials (RCTs) in
      which Tripterygium glycosides were employed, either alone or as an adjuvant
      treatment with disease-modifying antirheumatic drugs (DMARDs), in patients with
      LORA. The selection of studies, data extraction, and validation were performed
      independently by 2 reviewers. The Cochrane risk-of-bias criteria were used for
      evaluating the quality of the included studies. Settings * The study was
      conducted at Changzhou University (Changzhou, China), Nanjing University of
      Chinese Medicine (Nanjing, China), and the hospital affiliated with Nanjing
      University of Chinese Medicine (Nanjing, China). Participants * Studies including
      patients aged 60 y or older with RA in any of their peripheral joints were
      included in the meta-analysis. Intervention * All participants in the included
      studies were administered Tripterygium glycosides, either alone or together with
      other DMARDs, for at least 3 mo. Outcome Measures * The primary outcomes included
      (1) the swollen joint count (SJC) and (2) the tender joint count (TJC). The
      secondary outcomes included the erythrocyte sedimentation rate (ESR) and the
      level of C-reactive protein (CRP). Results * Four RCTs met the inclusion
      criteria, and most of them were of low methodological quality. The results of the
      current meta-analysis indicated that Tripterygium glycosides plus DMARD therapy,
      when compared with DMARD therapy alone, showed a favorable effect: (1) on the
      SJC, with the mean difference (MD) = -1.58, 95% confidence interval (CI) = -1.64
      to -1.51, and P < .01; (2) on the TJC, with the MD = -1.71, 95% CI = -2.26 to 
      1.15, and P < .01; (3) on the CRP levels, with the MD = -9.96, 95% CI = -10.96 to
      -8.96, and P < .01; and (4) on the ESR, with MD = -10.74, 95% CI = -12.47 to 
      9.00, and P < .01. In addition, the groups treated with Tripterygium glycosides
      were not superior to the intervention groups that did not use Tripterygium
      glycosides in terms of decreasing adverse events. Conclusions * A lack of
      sufficient trials contributed to the small sample size of the combined, eligible
      RCTs, and it was difficult to draw firm conclusions on the positive effects of
      Tripterygium glycosides and on their efficacy as an effective intervention for
      treating RA. A high risk of bias existed among the available RCTs. Further work
      with more RCTs on a larger patient population is necessary to confirm the
      efficacy and safety of Tripterygium glycosides for treating LORA.

PMID- 27866180
TI  - Positive Effects of Uyakujunkisan Therapy (Kampo Medicine) for Postherpetic
      Neuralgia With Concomitant Pregabalin: Two Case Reports With a Literature Review.
AB  - Context * The hallmark of herpes zoster (HZ) is a painful, blistering rash, but
      neuropathic pain can persist beyond the clearing of the rash and is diagnosed as
      postherpetic neuralgia (PHN), a chronic pain syndrome. However, the pain in PHN
      is often refractory to treatment. Objective * The study investigated the ability
      of Uyakujunkisan (UJS), or Kampo medicine, a traditional herbal medicine, to
      treat PHN successfully. Design * The study was observational, with discussion of
      2 cases. Setting * The study took place in the Department of Japanese Oriental
      Medicine at Gunma Central and General Hospital (Maebashi, Gunma, Japan).
      Participants * The participants in cases 1 and 2 were a 70-y-old male and a 70-y
      old female, respectively. The woman in case 2 also had rheumatoid arthritis. Both
      had been treated for HZ with antiviral drugs but continued to experience pain and
      were diagnosed with PHN. Intervention * Both participants were treated with a
      decoction of UJS that was administered 3 */d before meals. Outcome Measures * The
      patients completed a visual analogue scale. Results * In case 1, the patient's
      pain had almost disappeared after 8 wk of treatment. In case 2, the patient's
      pain had disappeared by 4 mo after starting the UJS treatment. Conclusions *
      Treatment with UJS may be a useful option as a therapeutic strategy for
      refractory PHN, especially in older adults.

PMID- 27866181
TI  - Dysbiosis or Adaptation: How Stable Is the Gut Microbiome?
AB  - No Abstract Available.

PMID- 27866182
TI  - Homeopathic Treatment of Overweight and Obesity in Pregnant Women With Mental
      Disorders: A Double-blind, Controlled Clinical Trial.
AB  - Context * Worldwide, 35 million people suffer from obesity. Mental disorders have
      been associated with being overweight or obese. Considerable evidence has shown a
      correlation between stress and the use of homeopathy and stress and obesity.
      However, few studies have examined the relationship between weight loss and
      homeopathic treatment of obesity. Objective * The study intended to evaluate the
      efficacy of a homeopathic treatment in preventing excessive weight gain during
      pregnancy in overweight or obese women who were suspected of having a common
      mental disorder. Design * The study was a randomized, controlled, double-blinded
      clinical trial. Setting * The study took place at the Center for the Social
      Support of Motherhood (Sao Paulo, Brazil). Participants * Participants were
      pregnant women who were enrolled at the center. Intervention * For the
      homeopathic group, 9 drugs were preselected, including (1) Pulsatilla nigricans,
      (2) Sepia succus, (3) Lycopodium clavatum, (4) sulphur, (5) Lachesis
      trigonocephalus, (6) Nux vomica, (7) Calcarea carbonica, (8) phosphorus; and (9)
      Conium maculatum. From those 9 drugs, 1 was prioritized for administration for
      each participant. After the first appointment, a reselection or selection of a
      new, more appropriate drug occurred, using the list of preselected drugs. The
      dosage was 6 drops orally 2 */d, in the morning and at night, on 4 consecutive
      days each wk, with an interval of 3 d between doses, up until the next
      appointment medical appointment. The control group received the equivalent
      placebo drug. Both groups also received a diet orientation. Outcome Measures * We
      evaluated pregnant women who were overweight or had class 1 or 2 obesity and were
      suspected of having a common mental disorder, with no concomitant diseases, in 2
      groups: those receiving a placebo (control group, n = 72); and those receiving
      homeopathic treatment (homeopathy group, n = 62). Weight change during pregnancy
      was defined as the difference between the body mass index (BMI) at the initial
      evaluation and that recorded at the final evaluation, adjusted for 40 wk of
      gestation. In addition, the APGAR index in the newborn was evaluated as a
      possible complication. Results * The mean variation between baseline BMI and BMI
      at week 40 of gestation was +4.95 kg/m2 in the control group and +5.05 kg/m2 in
      the homeopathy group. The difference between the 2 groups was not significant (P
      = .815; 95% confidence interval [CI], -0.916 to 0.722). APGAR 10 at 5 min
      (59.6%in homeopathy group and 36.4% among control) was statistically significant
      (P = .016). Conclusions * Homeopathy does not appear to prevent excessive body
      mass gain in pregnant women who are overweight or obese and suspected of having a
      common mental disorder. Homeopathy did not change the APGAR score to modified
      clinical attention at delivery room. However, the evidence observed at APGAR 10
      at minute 5 suggests that homeopathy had a modulating effect on the vitality of
      newborns, warranting further studies designed to investigate it.

PMID- 27866183
TI  - Resolution of Allergic Rhinitis and Reactive Bronchospasm With Supplements and
      Food-specific Immunoglobulin G Elimination: A Case Report.
AB  - Context * Allergies are a common affliction, whether they are respiratory, food
      related, or dermatological. People often resort to continuous use of over-the
      counter medications, such as antihistamines, to manage their symptoms.
      Controversy still remains over testing serum immunoglobulin (Ig) G to diagnose
      food allergies. Objective * This study intended to examine the benefits of
      treatment of a pediatric patient with natural supplements and an elimination diet
      for IgG food allergies. Design * The research team reported a case study. Setting
      * The study was conducted at Southwest Naturopathic Medical Center (Tempe, AZ,
      USA). Participant * The participant was a 10-y-old Caucasian female who had
      diagnoses of allergic rhinitis and reactive bronchospasm, the second of which was
      exacerbated by allergens such as wheat, perfumes, and seasonal flora.
      Intervention * Following testing for IgE- and IgG-reactive foods, the patient was
      treated with natural supplements to reduce her allergic responses and was
      instructed to make dietary changes to eliminate the IgG-reactive foods. Outcome
      Measures * The patient's symptom severity was tracked starting 1 mo after her
      initial visit to Southwest Naturopathic Medical Center. The severity was based on
      the patient's subjective reports about her congestion to her mother and on her
      mother's observations of the effect of symptoms on her attention and school
      performance. The bronchospasm severity was based on the frequency of a sensation
      of wheezing and chest tightness, the frequency of inhaler use, and the occurrence
      of any exacerbation of symptoms with acute respiratory illness Results * After 1
      mo, in which the patient used the natural supplements, she experienced a 90%
      improvement in coughing; a 70% improvement in nasal congestion; less chest
      tightness; and no need for use of loratadine, diphenhydramine, or albuterol. At
      the 8-mo follow-up visit, her nasal congestion was reported to be entirely gone.
      Conclusions * The case demonstrates the effectiveness of natural supplements and
      a diet eliminating IgG-reactive foods in the treatment and management of
      pediatric allergic rhinitis and reactive bronchospasm.

PMID- 27866184
TI  - The Gut-Brain Axis: Autoimmune and Neuroimmune Disorders.
AB  - No Abstract Available.

PMID- 27866185
TI  - Wilms Tumor 1 (WT1) mRNA Expression Level at Diagnosis Is a Significant
      Prognostic Marker in Elderly Patients with Myelodysplastic Syndrome.
AB  - BACKGROUND/AIMS: A high expression of Wilms tumor 1 (WT1) mRNA occurs in most
      cases of acute leukemia and myelodysplastic syndrome (MDS). Although there are
      many reports suggesting that acute myeloid leukemia patients with high expression
      levels of WT1 mRNA have a relatively poor long-term survival, there are few
      reports addressing the relationship between WT1 levels and prognosis in MDS.
      METHODS: We retrospectively analyzed 42 elderly patients with MDS whose WT1
      levels at diagnosis were available, and we assessed the relationships between WT1
      levels in peripheral blood and preexisting prognostic factors such as World
      Health Organization prognostic scores and Revised International Prognostic
      Scoring System risk categories, bone marrow blast percentages, and chromosomal
      abnormalities linked to a poor prognosis. We also evaluated the relationship
      between WT1 levels and prognosis. RESULTS: WT1 levels were significantly
      different between high- and low-risk MDS patients (p < 0.05). There was a trend
      towards a significant difference between those with and those without poor
      prognostic chromosomal rearrangements (p = 0.051). Moreover, the overall survival
      and progression-free survival were significantly worse in elderly patients with
      higher levels of WT1 (p = 0.00039 and p = 0.00077, respectively). CONCLUSIONS:
      The WT1 mRNA expression level at diagnosis may be a significant independent
      prognostic marker for elderly patients with MDS.

PMID- 27866186
TI  - Consequences of Stimulus Type on Higher-Order Processing in Single-Sided Deaf
      Cochlear Implant Users.
AB  - Single-sided deaf subjects with a cochlear implant (CI) provide the unique
      opportunity to compare central auditory processing of the electrical input (CI
      ear) and the acoustic input (normal-hearing, NH, ear) within the same individual.
      In these individuals, sensory processing differs between their two ears, while
      cognitive abilities are the same irrespectively of the sensory input. To better
      understand perceptual-cognitive factors modulating speech intelligibility with a
      CI, this electroencephalography study examined the central-auditory processing of
      words, the cognitive abilities, and the speech intelligibility in 10
      postlingually single-sided deaf CI users. We found lower hit rates and prolonged
      response times for word classification during an oddball task for the CI ear when
      compared with the NH ear. Also, event-related potentials reflecting sensory (N1)
      and higher-order processing (N2/N4) were prolonged for word classification
      (targets versus nontargets) with the CI ear compared with the NH ear. Our results
      suggest that speech processing via the CI ear and the NH ear differs both at
      sensory (N1) and cognitive (N2/N4) processing stages, thereby affecting the
      behavioral performance for speech discrimination. These results provide objective
      evidence for cognition to be a key factor for speech perception under adverse
      listening conditions, such as the degraded speech signal provided from the CI.

PMID- 27866187
TI  - A Pilot Study Examining the Effects of 8-Week Whey Protein versus Whey Protein
      Plus Creatine Supplementation on Body Composition and Performance Variables in
      Resistance-Trained Women.
AB  - AIMS: We performed a pilot study examining the effects of whey protein and
      creatine supplementation (PRO + CRE group) versus whey protein supplementation
      (PRO group) alone on body composition and performance variables in a limited
      number of resistance-trained women. METHODS: Seventeen resistance-trained women
      (21 +/- 3 years, 64.7 +/- 8.2 kg, 23.5 kg/m2, 26.6 +/- 4.8% body fat, >6 months
      of training) performed a 4-day per week split-body resistance training program
      for 8 weeks. Subjects ingested either 24 g PRO (n = 9) or 24 g whey plus 5 g
      creatine monohydrate (PRO + CRE, n = 8) following each exercise bout. At baseline
      (T1), 4 weeks (T2) and 8 weeks (T3), body composition was measured by dual X-ray
      absorptiometry (DXA), strength measures (leg press and bench press one repetition
      maximum) and lower-body power measures were determined. RESULTS: DXA lean mass
      increased from T1 to T3 in both groups (PRO: +2.5 kg, p < 0.001; PRO + CRE: +2.5
      kg, p < 0.001), although no differences between groups were observed. Compared to
      T1 values, performance measures similarly increased in both groups from T1 to T3
      although, no between-group differences were observed. CONCLUSIONS: PRO + CRE did
      not enhance training adaptations compared to PRO, albeit studies employing longer
      term interventions with larger sample sizes are needed in order to confirm or
      disprove our findings.

PMID- 27866188
TI  - Feasibility of Laryngeal Mask Airway Device Placement in Neonates.
AB  - BACKGROUND: The laryngeal mask airway (LMA) has been used in adult and pediatric
      populations for decades. While the familiarity of its use in the neonatal
      population is increasing, there are few data investigating this. OBJECTIVE: The
      objective of this study was to determine the feasibility of LMA placement in
      neonates by investigating the time and number of attempts required for successful
      placement and physiologic stability during the placement of the device. METHODS:
      This study is one component of a national, multicenter, randomized controlled
      trial investigating surfactant administration through an LMA in neonates.
      Videotape of LMA placement was reviewed to determine the total procedure time and
      the number of attempts required to successfully place the device. Heart rate and
      oxygen saturation (SaO2) were analyzed as change from baseline, in order to
      examine physiologic stability during device placement. RESULTS: Videotape and
      physiologic data were analyzed for 36 infants. Gestational age ranged from 293/7
      to 354/7 weeks (mean 33 +/- 1.7) with the birth weight ranging from 1,290 to
      3,180 g (mean 2,006 +/- 482). Average total procedure time was 88 s (+/-136) with
      64% of the procedures successfully completed in <35 s. Successful placement was
      achieved on the first attempt in 69% of the cases. Compared to baseline, heart
      rate increased by an average of 1 bpm (+/-4.5) and SaO2 decreased an average of
      6% (+/-7). CONCLUSIONS: Successful placement was achieved in the majority of
      patients in <35 s and required only one attempt. Physiologic parameters were
      maintained close to baseline, measured by minimal fluctuation in heart rate and
      SaO2 during the procedure. Placement of the LMA is feasible in neonates.

PMID- 27866189
TI  - Liver Transplantation in Wilson's Disease with Neurological Impairment:
      Evaluation in 4 Patients.
AB  - BACKGROUND: The aim of this work is to report our early experiences about the
      benefits of liver transplantation (LT) in the treatment of persistent
      neurological symptoms in Wilson's disease (WD) patients. METHODS: We describe our
      findings in 4 WD patients with neurological impairment or symptoms treated by LT:
      2 patients had transplants due to worsening of neurological symptoms despite long
      term appropriate medical treatment. The other 2 required LT because of symptoms
      associated with liver failure. Patients were evaluated using the modified Rankin
      scale and the Unified Wilson's Disease Rating Scale (UWDRS). RESULTS: The 4
      patients experienced neurological improvement after LT. The pre-LT Rankin score
      of the 2 patients transplanted due to neurological impairment was 4 compared to 3
      and 2, respectively, post LT. The pre-LT Rankin scores of the 2 WD cases
      transplanted because of hepatic failure were 1 and 2, respectively, compared to 0
      in both cases post LT. UWDRS score improved in 2 cases and remained stable in 1
      less severely impaired case. Brain MRI abnormalities proved partially reversible
      in 3 patients and remained stable for 1 patient. CONCLUSIONS: These results
      suggest that LT could be envisaged for neurologically impaired WD patients.

PMID- 27866190
TI  - Role of MCPIP1 in the Endothelial-Mesenchymal Transition Induced by Silica.
AB  - BACKGROUND: Silicosis is characterized by the accumulation of fibroblasts and the
      excessive deposition of extracellular matrix. Fibroblast generation via
      endothelial-mesenchymal transition (EndMT) is one process responsible for this
      accumulation of fibroblasts. However, the mechanisms underlying EndMT remain
      unknown. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to
      SiO2 (50 ug/cm2). Specific endothelial and mesenchymal markers were evaluated
      using immunofluorescence and western blot analysis. Functional changes were
      evaluated by analyzing cell migration and proliferation. LC3-adenovirus
      transfections were performed, and changes in autophagy were measured using a
      marker of autophagy. RESULTS: SiO2 induced decreases in the endothelial cell
      specific markers in HUVECs while dramatically increasing mesenchymal cell product
      levels and mesenchymal functions. Although MCPIP1 expression increased in
      parallel with the increase in specific mesenchymal cell products, the MCPIP1
      expression level was not consistent with the observed decrease in specific
      endothelial marker expression. Autophagy mediated the effects of MCPIP1, as
      rapamycin and 3-MA enhanced and attenuated the effect of SiO2 on HUVECs,
      respectively. MAPKs and the PI3K/Akt pathway were involved in the regulation of
      MCPIP1 by SiO2, and Pyk2 and MLC-2 mediated cell migration. CONCLUSION: Our
      findings reveal a new potential function of MCPIP1, suggesting a possible
      mechanism of fibrosis in pulmonary silicosis.

PMID- 27866191
TI  - The Long Non-Coding RNA LncRNA8975-1 is Upregulated in Hypertrophic Scar
      Fibroblasts and Controls Collagen Expression.
AB  - BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) are thought to play crucial roles
      in human diseases. However, the function of lncRNAs in hypertrophic scar
      formation remains poorly understood. METHODS: In this study, we investigated the
      expression of lncRNA8975-1 in hypertrophic scar tissues and fibroblasts by
      quantitative reverse transcription PCR (qRT-PCR). To investigate its function,
      overexpression and knockdown of lncRNA8975-1 were performed using lentivirus
      infection and Stealth RNAi transfection, respectively. Cell proliferation was
      detected by CCK-8 assay. The protein levels of collagens and alpha-smooth muscle
      actin (alpha-SMA) were analysed by western blot. RESULTS: We found that
      lncRNA8975-1 was overexpressed in hypertrophic scar tissues and dermal
      fibroblasts. Overexpression of lncRNA8975-1 inhibited cell proliferation and
      reduced the protein expression levels of COL1A2, COL1A1, COL3A1 and alpha-SMA in
      hypertrophic scar fibroblasts, whereas knockdown of lncRNA8975-1 had the opposite
      effect. CONCLUSION: Our results show that the long non-coding RNA lncRNA8975-1 is
      upregulated in hypertrophic scar fibroblasts; furthermore, it inhibits fibroblast
      proliferation and reduces collagen and alpha-SMA expression. Further studies on
      the mechanisms regulated by lncRNA8975-1 would lead to a better understanding of
      the pathogenesis of hypertrophic scar formation.

PMID- 27866192
TI  - Dietary Genistein Rescues Reduced Basal Chloride Secretion in Diabetic Jejunum
      via Sex-Dependent Mechanisms.
AB  - BACKGROUND/AIMS: The goal of this study was to determine the effect of dietary
      genistein (naturally occurring phytoestrogen) on jejunal secretory function in a
      clinically relevant model of diabetes and obesity, the leptin-defIcient ob/ob
      mouse. METHODS: We measured transepithelial short circuit current (Isc), across
      freshly isolated segments of jejunum from 12-week old male and female ob/ob and
      lean C57Bl/6J mice fed a genistein diet (600 mg genistein/kg diet) for 4-weeks.
      Separate segments of jejunum were frozen for western blot determination of key
      proteins involved in secretory transport. RESULTS: Basal Isc was signifIcantly
      decreased (by 33%, P<0.05) in ob/ob females versus leans, and genistein-diet
      reversed this. Similarly, in males, basal Isc was decreased (by 47%, P<0.05) in
      ob/ob mice versus leans, and genistein-diet reversed this. Inhibition with either
      clotrimazole (100 uM, bilateral) or ouabain (100 uM, basolateral) was
      signifIcantly reduced in ob/ob mice compared to leans (P<0.05), and genistein
      diet reversed clotrimazole-sensitive inhibition in ob/ob females, and reversed
      the ouabain-sensitive inhibition in males (indicating sex-dependent mechanisms).
      Our data suggested that PDE3 levels were dysregulated in ob/ob females and
      genistein reversed this. Expression of total CFTR (normalized to actin) was
      signifIcantly decreased ~80% (P<0.05) in all ob/ob mice compared to leans, and
      genistein-diet was without effect. Expression of total NKCC1 (normalized to
      actin) was signifIcantly decreased ~80% (P<0.05) in ob/ob male mice versus leans,
      and genistein-diet reversed this. CONCLUSIONS: Our data suggests that the reduced
      basal jejunal Isc in ob/ob female mice is a consequence of reduced CFTR
      expression, decreased activities of the basolateral KCa channel and Na+/K+
      ATPase, and in male mice reduced basal jejunal Isc is a consequence of reduced
      CFTR and NKCC1 expression, along with decreased activities of the basolateral KCa
      channel and Na+/K+-ATPase. Genistein-diet has beneficial effects on basal Isc
      mediated by sex-dependent mechanisms in diabetic mice: in females via increased
      KCa-sensitive Isc and in males via increased Na+/K+-ATPase activity and increased
      NKCC1 expression. Improved understanding of intestinal dysfunctions in the ob/ob
      jejunum, may allow for the development of novel drug targets to treat obesity and
      diabetes, and may also be of benefit in CF-related diabetes.

PMID- 27866194
TI  - Efficacy of Bevacizumab in the First-Line Treatment of Patients with RAS
      Mutations Metastatic Colorectal Cancer: a Systematic Review and Network Meta
      Analysis.
AB  - BACKGROUND/AIMS: Whether patients with RAS mutation metastatic colorectal cancer
      (mCRC) obtain benefits from bevacizumab added to first-line chemotherapy remains
      unclear. METHODS: PubMed, Cochrane Systematic Reviews, the Cochrane Collaboration
      Central Register of Controlled Clinical Trials, ClinicalTrials.gov, and the
      American Society of Clinical Oncology and European Society for Medical Oncology
      databases were searched to identify abstracts for randomized controlled trials
      (RCTs) evaluating the efficacy of bevacizumab for the first-line treatment of
      patients with RAS mutations mCRC from inception to the end of April 2016. Hazard
      ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were
      estimated. RESULTS: Ten eligible papers reporting six RCTs were included. In the
      network meta-analysis of patients with RAS mutations, bevacizumab + chemotherapy
      prolonged PFS compared with chemotherapy alone (HR 0.75, 95% CI 0.51-1.10), but
      the difference was not statistically significant. Bevacizumab + chemotherapy did
      not prolong OS compared with chemotherapy alone (HR 1.10, 95% CI 0.73-1.66).
      CONCLUSION: There was insufficient evidence to definitively state that patients
      with RAS mutations mCRC could benefit from bevacizumab combined with chemotherapy
      as first-line treatment.

PMID- 27866193
TI  - Mixed Aqueous Extract of Salvia Miltiorrhiza Reduces Blood Pressure through
      Inhibition of Vascular Remodelling and Oxidative Stress in Spontaneously
      Hypertensive Rats.
AB  - BACKGROUND/AIMS: Salvia miltiorrhiza (SM) contains four major aqueous active
      ingredients, which have been isolated, purified and identified as danshensu
      (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic
      aldehyde (PAL), totally abbreviated as SABP. Although SM is often used to treat
      various cardiovascular diseases in traditional Chinese medicine, the efficacy and
      function of optimal compatibility ratio of SM's active ingredients (SABP) in the
      prevention and treatment of cardiovascular diseases remain uncertain. This study
      investigated antihypertensive effect and underlying mechanisms of SABP vs. SM
      lyophilized powder (SMLP) in spontaneously hypertensive rats (SHR) and to
      establish the ratio of the optimal compatibility of DSS, Sal-A, Sal-B and PAL in
      improving cardiovascular functions. METHODS: The SHRs were treated with either
      SABP or SMLP and their systolic blood pressures (SBP) were monitored. The
      isolated thoracic aorta of SHRs was segregated for immunohistochemistry,
      Hematoxylin-Eosin stain and mRNA and protein expression of NOX4, TGF-beta1, Col
      I, ET-1, alpha-SMA and Smad7. Moreover, the adventitial fibroblasts (AFs) were
      isolated and cultured from SD rats' aorta and the reactive oxygen species (ROS)
      production was determined after SABP or SMLP treatment. RESULTS: SABP, but not
      SMLP, significantly reduced SBP, which were accompanied by the inhibited
      morphological changes in the thoracic aorta and the reduced mRNA and protein
      expression of NOX4, TGF-beta1, Col-I, ET-1 and alpha-SMA, but the increased Smad
      7 expression in SHRs. Moreover, SABP also resulted in a decreased ROS production
      in AFs of SD rats. CONCLUSIONS: These results indicate that SABP, but not SMLP,
      treatment potently inhibits hypertension through improvements of vascular
      remodeling and oxidative stress. The present study provides new evidence that the
      efficacy and function from optimal compatibility ratio of SM active ingredients
      is much better than its lyophilized powder, which represents a strategy to
      develop SM's new beneficial effect in improving cardiovascular functions.

PMID- 27866195
TI  - Comparison of Telbivudine and Entecavir Therapy on Nephritic Function and Drug
      Resistance in Patients with Hepatitis B Virus-Related Compensated Cirrhosis.
AB  - BACKGROUND: To compare the impact of telbivudine (LDT) and entecavir (ETV)
      administration on nephritic function. METHOD: One hundred thirty patients
      diagnosed with hepatitis B virus (HBV)-related compensated cirrhosis were
      randomly divided into LDT (600 mg/d) or ETV (0.5 mg/d) groups. RESULTS: The drug
      resistance rate was higher following LDT treatment compared to ETV treatment
      (16.9% vs. 1.5%, P=0.0006). The mean creatinine level decreased compared to
      baseline in the LDT group (0.81 vs. 0.94 mg/dl, P=0.000). The change in median
      glomerular filtration rate (eGFR) compared to baseline in the LTD and ETV groups
      was 22.3 and -3.3, respectively, at 2 years (P=0.000). In patients with mild
      nephritic injury (eGFR< 90 ml/min/1.73m2), the median eGFR increased by 28.0
      ml/min/1.73m2 in the LDT group and decreased by 4.3 ml/min/1.73m2 in the ETV
      group (p=0.000). The eGFR in 88.5% of patients (23/26) from the LDT group
      increased > 90 ml/min/1.73m2. The percentage of patients with an eGFR > 90
      ml/min/1.73m2 increased from 60.0% to 92.3% in the LDT group and from 64.6% to
      69.2% in the ETV group. CONCLUSION: In patients with HBV-related compensated
      cirrhosis, LDT treatment was more effective in protecting nephritic function and
      was associated with a higher drug resistance rate, but did not contribute to a
      better outcome compared with ETV treatment.

PMID- 27866197
TI  - Rs56288038 (C/G) in 3'UTR of IRF-1 Regulated by MiR-502-5p Promotes Gastric
      Cancer Development.
AB  - BACKGROUND/AIMS: Interferon regulatory factor 1 (IRF-1) has been shown to
      function as a transcriptional activator or repressor of a variety of target
      genes. However, its upstream, non-coding RNA-related regulatory capacity remains
      unknown. In this study, we focus on the miRNA-associated single nucleotide
      polymorphisms (SNPs) in the 3'untranslated region (UTR) of IRF-1 to further
      investigate the functional relationship and potential diagnostic value of the
      SNPs and miRNAs among Chinese gastric cancer (GC) patients. METHODS: We performed
      a case-control study with 819 GC patients and 756 cancer-free controls.
      Genotyping by realtime PCR assay, cell transfection, and the dual luciferase
      reporter assay were used in our study, and the 5-year overall survival rate and
      relapse-free survival rate in different groups were investigated. RESULTS: We
      found that patients suffering from Helicobacter pylori (Hp) infection were the
      susceptible population compared to controls. SNP rs56288038 (C/G) in IRF-1 3'UTR
      was involved in the occurrence of GC by acting as a tumor promoter factor. SNP
      rs56288038 (C/G) could be up-regulated by miR-502-5p, which caused a down
      regulation of IRF-1 in cell lines and decreased apoptosis induced by IFN-gamma.
      Carrying the G genotype was related to significantly low expression of IRF-1 and
      Hp infection, poor differentiation, big tumor size, invasion depth, as well as
      the high probability of metastasis, and moreover, the C/G SNP was associated with
      shorter survival of GC patients with five years of follow-up study. CONCLUSIONS:
      our findings have shown that the SNP rs56288038 (C/G) in IRF-1 3'UTR acted as a
      promotion factor in GC development through enhancing the regulatory role of miR
      502-5p in IRF-1 expression.

PMID- 27866196
TI  - Down-Regulation of Protein Kinase C-epsilon by Prolonged Incubation with PMA
      Inhibits the Proliferation of Vascular Smooth Muscle Cells.
AB  - BACKGROUND/AIMS: Phorbol myristate acetate (PMA) exerts a pleiotropic effect on
      the growth and differentiation of various cells. Protein kinase Cs (PKCs) plays a
      central role in mediating the effects of PMA on cells. The present study
      investigated whether the down-regulation of protein kinase C-epsilon (PKC
      epsilon) is involved in the inhibition of vascular smooth muscle cell (VSMC)
      proliferation caused by prolonged PMA incubation. METHODS: Using cell counting,
      Cell Counting Kit-8 (CCK-8) and EdU incorporation assay on VSMCs, we evaluated
      the inhibitory effects of prolonged incubation of PMA, of lentiviruses carrying
      the short-hairpin RNAs (shRNA) of PKC-epsilon and of the PKC-epsilon inhibitor
      peptide on the proliferation and viability of cells. The effect of PKC-epsilon
      down-regulation on growth of rat breast cancer SHZ-88 cells was also measured.
      RESULTS: The prolonged incubation of VSMCs with PMA for up to 72 hours resulted
      in attenuated cell growth rates in a time-dependent manner. The expression of PKC
      epsilon, as assessed by Western blotting, was also decreased accordingly.
      Notably, the number of EdU-positive cells and the cell viability of VSMCs were
      decreased by shRNA of PKC-epsilon and the PKC-epsilon inhibitor peptide,
      respectively. The proliferation of rat breast cancer SHZ-88 cells was also
      attenuated by lentivirus-induced shRNA silencing of PKC-epsilon. CONCLUSIONS:
      Prolonged incubation of PMA can inhibit the expression of PKC-epsilon. The effect
      results in the inhibition of VSMC proliferation. PKC-epsilon silencing can also
      attenuate breast cancer cell growth, suggesting that PKC-epsilon may be a
      potential target for anti-cancer drugs.

PMID- 27866198
TI  - Proteomic Analysis and Identification of Paracrine Factors in Mesenchymal Stem
      Cell-Conditioned Media under Hypoxia.
AB  - BACKGROUND/AIMS: We previously showed that a hypoxic environment modulates the
      antiarrhythmic potential of mesenchymal stem cells. METHODS: To investigate the
      mechanism by which secreted proteins contribute to the pathogenesis of
      antiarrhythmic potential in mesenchymal stem cells, we used two-dimensional
      electrophoresis combined with MALDI-TOF-MS to perform a proteomic analysis to
      compare the paracrine media produced by normoxic and hypoxic cells. RESULTS: The
      proteomic analysis revealed that 66 protein spots out of a total of 231 matched
      spots indicated differential expression between the normoxic and hypoxic
      conditioned media of mesenchymal stem cells. Interestingly, two tropomyosin
      isoforms were dramatically increased in the hypoxic conditioned medium of
      mesenchymal stem cells. An increase in tropomyosin was confirmed using Western
      blot to analyze the conditioned media between normoxic and hypoxic cells. In a
      network analysis based on gene ontology (GO) Molecular Function by GeneMANIA
      analysis, most of the identified proteins were found to be involved in the
      regulation of heart processes. CONCLUSION: Our results show that hypoxia up
      regulates tropomyosin and other secreted proteins which suggests that tropomyosin
      may be involved in regulating proarrhythmic and antiarrhythmic functions.

PMID- 27866199
TI  - The Experience of Relations in Persons with Dementia: A Systematic Meta
      Synthesis.
AB  - BACKGROUND: Dementia influences a person's experience of social relationships, as
      described in several studies. In this systematic meta-synthesis of qualitative
      studies, we aim to interpret and synthesize the experiences of persons with
      dementias and their relations with others. SUMMARY: Living with dementia changes
      life, leading to new social roles and different social statuses. Persons with
      dementia experience being disconnected and dependent on others, feeling like
      being a burden, and being a person who is treated in paternalistic ways. Family,
      friends and others with dementia might play significant roles in their ability to
      maintain a meaningful life. Key Messages: Three categories emerged from the data,
      change in life, change in relations, and maintenance of meaningful aspects in
      life; these categories are intertwined and essential in sustaining a lifeline for
      persons with dementia. The comprehensive meaning of the material is understood as
      the expression: Living a meaningful life in relational changes.

PMID- 27866200
TI  - Implementation of a Simplified Regional Citrate Anticoagulation Protocol for Post
      Dilution Continuous Hemofiltration Using a Bicarbonate Buffered, Calcium
      Containing Replacement Solution.
AB  - BACKGROUND/AIMS: Recent updates to the Nikkiso Aquarius continuous renal
      replacement therapy (CRRT) platform allowed us to develop a post-dilution
      protocol for regional citrate anticoagulation (RCA) using standard bicarbonate
      buffered, calcium containing replacement solution with acid citrate dextrose
      formula-A as a citrate source. Our objective was to demonstrate that the protocol
      was safe and effective. METHODS: Prospective audit of consecutive patients
      receiving RCA for CRRT within intensive care unit, who were either
      contraindicated to heparin or had poor filter lifespan (<12 h for 2 consecutive
      filters) on heparin. RESULTS: We present the first 29 patients who used 98
      filters. After excluding 'non-clot' filter loss, 50% had a duration of >27 h.
      Calcium supplementation was required for 30 (30%) filter circuits, in 17 of 29
      (58%) patients. One patient discontinued the treatment due to metabolic
      alkalosis, but there were no adverse bleeding events. CONCLUSION: Post-dilution
      RCA system is effective and simple to use on the Aquarius platform and results in
      comparable filter life for patients relatively contraindicated to heparin.

PMID- 27866201
TI  - Comparative Analysis of Gene Regulatory Network Components in the Auditory
      Hindbrain of Mice and Chicken.
AB  - The neurons in the mammalian and avian auditory hindbrain nuclei share a number
      of significant morphological and physiological properties for fast, secure and
      precise neurotransmission, such as giant synapses, voltage-gated K+ channels and
      fast AMPA receptors. Based on the independent evolution of the middle ear in
      these two vertebrate lineages, on different embryonic origins of the nuclei and
      on marked differences on the circuit level, these similarities are assumed to
      reflect convergent evolution. Independent acquisition of similar phenotypes can
      be produced by divergent evolution of genetic mechanisms or by similar molecular
      mechanisms. The distinction between these two possibilities requires knowledge of
      the gene regulatory networks (GRNs) that orchestrate the development of auditory
      hindbrain structures. We therefore compared the expression pattern of GRN
      components, both transcription factors (TFs) and noncoding RNA, during terminal
      differentiation of the auditory hindbrain structures in mouse and chicken when
      neurons acquire their final morphological and electrophysiological properties. In
      general, we observed broad expression of these genes in the mouse auditory
      cochlear nucleus complex and the superior olivary complex at both postnatal day 4
      (P4) and at P25, and for the chicken at the equivalent developmental stages, i.e.
      embryonic day 13 (E13) and at P14-P17. Our data are in agreement with a model
      based on similar molecular mechanisms underlying terminal differentiation and
      maintenance of neuronal cell identity in the auditory hindbrain of different
      vertebrate lineages. This conservation might reflect developmental constraints
      arising from the tagmatic organization of rhombomeres and the evolutionarily
      highly conserved GRNs operating in these structures.

PMID- 27866202
TI  - The Evolution of Thyroid Function after Presenting with Hashimoto Thyroiditis Is
      Different between Initially Euthyroid Girls with and Those without Turner
      Syndrome.
AB  - AIM: To prospectively investigate, during a 5-year follow-up, whether the
      prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in
      euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS.
      DESIGN: In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid
      functional test results at HT diagnosis, we followed up the evolution of thyroid
      status over time. RESULTS: At the end of follow-up, the TS girls exhibited higher
      TSH levels, lower fT4 levels, and lower prevalence rates of both euthyroidism and
      subclinical hypothyroidism, but higher prevalence rates of both overt
      hypothyroidism and hyperthyroidism, irrespective of the karyotype. CONCLUSIONS:
      An association with TS is able to impair the long-term prognosis of thyroid
      function in girls with HT. Such an effect occurs irrespective of thyroid
      functional test results at HT diagnosis and is not necessarily linked with a
      specific karyotype.

PMID- 27866204
TI  - More Attention Should Be Paid to Monitoring of Abdominal Obesity among Children
      and Adolescents.

PMID- 27866203
TI  - Frontal Assessment Battery as a Useful Tool to Differentiate Mild Cognitive
      Impairment due to Subcortical Ischemic Vascular Disease from Alzheimer Disease.
AB  - BACKGROUND: Prominent executive dysfunction can differentiate vascular dementia
      from Alzheimer disease (AD). However, it is unclear whether the Frontal
      Assessment Battery (FAB) screening tool can differentiate subcortical ischemic
      vascular disease (SIVD) from AD at the pre-dementia stage. In addition, the
      neural correlates of FAB performance have yet to be clarified. METHODS: Patients
      with mild cognitive impairment (MCI) due to SIVD (MCI-V), MCI due to AD (MCI-A),
      and demographically matched controls completed the Mini-Mental State Examination,
      Taiwanese FAB (TFAB), Category Fluency, and Chinese Version of the Verbal
      Learning Test, and underwent magnetic resonance imaging. White matter
      hyperintensities were rated according to the Scheltens scale. RESULTS: TFAB total
      scale and its Orthographical Fluency subtest were the only measures that could
      differentiate MCI-V from MCI-A. Discriminative analysis showed that
      Orthographical Fluency scores successfully identified 73.2% of the cases with MCI
      V, with 85.0% sensitivity. Orthographical Fluency scores were specifically
      associated with lesion load within frontal periventricular, frontal deep white
      matter, and basal ganglia regions. CONCLUSION: The TFAB, and especially its 1-min
      Orthographical Fluency subtest, is a useful screening procedure to differentiate
      MCI due to SIVD from MCI due to AD. The discriminative ability is probably due to
      frontosubcortical white matter pathologies disproportionately involved in the two
      disease entities.

PMID- 27866205
TI  - Disparities in Kidney Transplantation Access among Korean Patients Initiating
      Dialysis: A Population-Based Cohort Study Using National Health Insurance Data
      (2003-2013).
AB  - BACKGROUND: The socioeconomic status of a person has an impact on his or her
      access to kidney transplantation as has been reported in western countries. This
      study examined the association between income level and kidney transplantation
      among chronic kidney disease patients undergoing dialysis in South Korea.
      METHODS: We analyzed data from 1,792 chronic kidney disease patients undergoing
      dialysis and listed in the Korean National Health Insurance Claim Database (2003
      2013). The likelihood of receiving the first kidney transplant over time was
      analyzed using competing risk proportional hazard models on time from initiating
      dialysis to receiving a transplant. RESULTS: Of 1,792 patients on dialysis, only
      184 patients (10.3%) received kidney transplants. Patients with medical aid had
      the lowest kidney transplantation rate (hazard ratio 0.29, 95% CI 0.16-0.51). A
      lower income level was significantly associated with a low kidney transplantation
      rate, after adjusting for covariates, compared to patients in the high-income
      level group. CONCLUSIONS: Our findings indicate that in South Korea, the total
      number of kidney transplants is remarkably low and there exists income disparity
      with regard to access to kidney transplantation. Thus, we suggest that plans be
      implemented to encourage organ donation and increase organ transplant
      accessibility for all patients irrespective of their socioeconomic status.

PMID- 27866208
TI  - Kidney Cancer Linked to Chronic Hepatitis in the Asia-Pacific: A Population-Based
      Analysis.
AB  - BACKGROUND: The association of renal cancer with viral hepatitis infection
      remains unclear. Using an insurance data set, this population-based case-control
      study evaluated the association of renal cancer with chronic hepatitis virus
      infection in an endemic area of hepatitis B virus (HBV) and hepatitis C virus
      (HCV) infection. METHODS: We enrolled 17,747 patients with renal cancer during
      the period from 2000 to 2011 from the National Health Insurance Research Database
      of Taiwan. The control group comprised 35,494 randomly selected people without
      renal cancer matched by age and gender to the patients in the study group. ORs
      were calculated to assess the association of chronic hepatitis virus infection
      with renal cancer by using logistic regression analysis. RESULTS: Renal cancer
      was associated with HBV and HCV infection (OR 1.38, 95% CI 1.24-1.54; OR 1.24,
      95% CI 1.07-1.44, respectively). An analysis stratified by gender and age
      revealed that young male HBV carriers had a higher risk of renal cancer compared
      with men without viral hepatitis (age <55 years: OR 1.94, 95% CI 1.57-2.39; 55<=
      age <64 years: OR 1.40, 95% CI 1.05-1.86). Male HCV-infected patients aged <55
      years (OR 1.90, 95% CI 1.11-3.26) and female HCV carriers aged between 55 and 64
      years (OR 1.59, 95% CI 1.00-2.53) had a significantly higher risk of renal cancer
      compared with their counterparts. CONCLUSIONS: Renal cancer is significantly
      associated with chronic hepatitis infection, particularly in younger HBV-infected
      men.

PMID- 27866206
TI  - Genome-Wide STAT3 Binding Analysis after Histone Deacetylase Inhibition Reveals
      Novel Target Genes in Dendritic Cells.
AB  - STAT3 is a master transcriptional regulator that plays an important role in the
      induction of both immune activation and immune tolerance in dendritic cells
      (DCs). The transcriptional targets of STAT3 in promoting DC activation are
      becoming increasingly understood; however, the mechanisms underpinning its role
      in causing DC suppression remain largely unknown. To determine the functional
      gene targets of STAT3, we compared the genome-wide binding of STAT3 using ChIP
      sequencing coupled with gene expression microarrays to determine STAT3-dependent
      gene regulation in DCs after histone deacetylase (HDAC) inhibition. HDAC
      inhibition boosted the ability of STAT3 to bind to distinct DNA targets and
      regulate gene expression. Among the top 500 STAT3 binding sites, the frequency of
      canonical motifs was significantly higher than that of noncanonical motifs.
      Functional analysis revealed that after treatment with an HDAC inhibitor, the
      upregulated STAT3 target genes were those that were primarily the negative
      regulators of proinflammatory cytokines and those in the IL-10 signaling pathway.
      The downregulated STAT3-dependent targets were those involved in immune effector
      processes and antigen processing/presentation. The expression and functional
      relevance of these genes were validated. Specifically, functional studies
      confirmed that the upregulation of IL-10Ra by STAT3 contributed to the
      suppressive function of DCs following HDAC inhibition.

PMID- 27866209
TI  - Local Ecological Knowledge about Endangered Primates in a Rural Community in
      Paraiba, Brazil.
AB  - The study of local ecological knowledge (LEK) fosters a better understanding of
      the relationship between humans and the environment. We assessed respondents'
      ecological knowledge of primates in a rural community located near the Atlantic
      Forest remnants in the state of Paraiba, Brazil. Populations of Alouatta belzebul
      (red-handed howler monkeys), Sapajus flavius (blonde capuchins), and Callithrix
      jacchus (the common marmoset) inhabit the region. We conducted 200 semi
      structured interviews and applied thematic content analysis, with weighting, to
      the responses to quantify the LEK. Respondents showed a low LEK, despite the
      community's proximity to forest remnants. However, the LEK was significantly
      higher among men, as well as among those who had a greater degree of contact with
      the primates. Age did not influence LEK. The studied community apparently does
      not intensively exploit the forest resources nor does it economically depend on
      primates, which may explain these individuals' low levels of knowledge about
      these animals. Such data may support future studies, as well as environmental
      education and action plans, especially for A. belzebul and S. flavius, both of
      which are endangered species and targets of the National Action Plan for the
      Conservation of the Primates of the Northeast.

PMID- 27866207
TI  - Post-Stroke Fatigue May Be Associated with the Promoter Region of a Monoamine
      Oxidase A Gene Polymorphism.
AB  - BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite
      reports of serotonergic involvement in the etiology of PSF, the potential
      contribution of serotonergic genes in the development of PSF needs to be
      investigated. METHODS: A total of 373 patients, who experienced ischemic stroke
      for PSF, were evaluated 3 months after the stroke. PSF was assessed using the
      Fatigue Severity Scale. The genomic DNA collected and stored in a -70 degrees C
      freezer was genotyped for 6 polymorphisms in genes associated with serotonin
      synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2
      rs4641528), transport (the promoter region of the serotonin transporter protein),
      and catabolism (the 30-bp functional variable number tandem repeat) polymorphism
      in the promoter region of monoamine oxidase A (MAO-A). RESULTS: Among the 373
      patients, 164 (44%) had PSF. All patients were ethnic Koreans. Of the 6
      polymorphisms examined, only one marker, that is, low-activity MAO-A was
      associated with PSF (p < 0.05) in female patients. Multiple logistic regression
      analyses showed that post-stroke depression (PSD; 95% CI 1.561-14.323, p = 0.006)
      and low MAO-A activity (95% CI 0.166-0.722, p = 0.005) were factors associated
      with PSF in female patients, whereas only PSD (95% CI 5.511-65.269, p = 0.000)
      was associated with PSF in male patients. CONCLUSIONS: Our findings suggest that
      PSF may be associated with a genetic polymorphism involving MAO-A, at least in
      female stroke patients.

PMID- 27866210
TI  - Body Composition in Very Preterm Infants: Role of Neonatal Characteristics and
      Nutrition in Achieving Growth Similar to Term Infants.
AB  - BACKGROUND: The identification of factors involved in the postnatal growth of
      preterm infants will help achieve growth similar to that of term infants.
      OBJECTIVES: As per protocol: to compare body composition in very preterm infants
      at term-corrected age (TCA) with that in term infants, and to explore
      relationships between neonatal characteristics and body composition in preterm
      infants. METHODS: Anthropometry, nutritional characteristics, and neonatal
      outcomes were prospectively collected in 26 preterm (<29 weeks) and 33 term (37
      40 weeks) infants. Body composition using dual-energy X-ray absorptiometry (DXA)
      was measured at TCA in preterm infants and between days 7 and 10 in term infants.
      RESULTS: Parenteral nutrition in preterm infants provided a mean of 2.9 +/- 0.2
      and 2.1 +/- 0.5 g/kg/day of intravenous amino acids and lipids, respectively,
      during the first week of life. The mean weight gain velocity from birth to DXA
      assessment was 12.1 +/- 1.4 g/kg/day. Compared with term infants, preterm infants
      at TCA were shorter and lighter, with a smaller head circumference, a lower
      weight estimated by DXA (2,960 +/- 552 vs. 3,843 +/- 377 g), and increased
      skinfold thicknesses. Fat mass percent (13.9 +/- 5.4%) and lean mass percent
      (84.7 +/- 5.6%) in preterm infants were similar to those in term infants (14.7 +/
      3.5 and 83.5 +/- 3.6%, respectively). Neonatal weight gain velocity in preterm
      infants was positively associated with lean mass (grams). CONCLUSION:
      Subcutaneous fat is increased in preterm infants. Higher protein intake in
      preterm infants might increase weight gain velocity and achieve a lean mass
      comparable to that of term infants.

PMID- 27866212
TI  - Expression of IL-1alpha and IL-6 is Associated with Progression and Prognosis of
      Human Cervical Cancer.
AB  - BACKGROUND IL-1alpha and IL-6 are associated with the prognosis of a wide range
      of cancers, but their value in cervical cancer remains controversial. The aim of
      this study was to investigate the expression of IL-1alpha and IL-6 in cervical
      cancer and their significance in clinical prognosis. MATERIAL AND METHODS The
      expression of IL-1alpha and IL-6 in 105 formalin-fixed, paraffin-embedded
      cervical cancer tissues and adjacent non-tumor tissues was examined by
      immunohistochemistry. The results were semi-quantitatively scored and analyzed by
      chi-square test. Patient overall survival (OS) data was collected by follow-up
      and analyzed by Kaplan-Meier analysis. RESULTS The expression level of both IL
      1alpha and IL-6 in cervical cancer tissue was higher than in adjacent non-tumor
      tissues (p<0.05). IL-1alpha expression was shown to be correlated with tumor
      size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor
      differentiation (p<0.05). IL-6 expression was shown to be correlated with tumor
      size, FIGO histology grade, and tumor differentiation (p<0.05). Patients with
      positive expression of IL-1alpha or IL-6 tended to have much shorter survival
      times than patients with negative expression. In addition, a multivariate Cox
      regression analysis demonstrated that IL-1alpha expression and lymph node
      metastasis were independent predictors of OS in cervical cancer patients.
      CONCLUSIONS The expression of IL-1alpha was significantly associated with tumor
      size, FIGO histology grade, lymph node metastasis, stromal invasion, and tumor
      differentiation. The expression of IL-6 was significantly associated with tumor
      size, FIGO histology grade, and tumor differentiation. Positive IL-1alpha and IL
      6 expression was significantly correlated with poor prognosis. They may be
      considered valuable biomarkers for prognosis and potential therapeutic targets
      for cervical cancer.

PMID- 27866211
TI  - Single-Nucleotide Polymorphisms of Genes Involved in Repair of Oxidative DNA
      Damage and the Risk of Recurrent Depressive Disorder.
AB  - BACKGROUND Depressive disorder, including recurrent type (rDD), is accompanied by
      increased oxidative stress and activation of inflammatory pathways, which may
      induce DNA damage. This thesis is supported by the presence of increased levels
      of DNA damage in depressed patients. Such DNA damage is repaired by the base
      excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms
      in BER-related genes. Therefore, we genotyped nine single-nucleotide
      polymorphisms (SNPs) in six genes encoding BER proteins. MATERIAL AND METHODS
      Using TaqMan, we selected and genotyped the following SNPs: c.-441G>A (rs174538)
      of FEN1, c.2285T>C (rs1136410) of PARP1, c.580C>T (rs1799782) and c.1196A>G
      (rs25487) of XRCC1, c.*83A>C (rs4796030) and c.*50C>T (rs1052536) of LIG3, c.
      7C>T (rs20579) of LIG1, and c.-468T>G (rs1760944) and c.444T>G (rs1130409) of
      APEX1 in 599 samples (288 rDD patients and 311 controls). RESULTS We found a
      strong correlation between rDD and both SNPs of LIG3, their haplotypes, as well
      as a weaker association with the c.-468T>G of APEXI which diminished after Nyholt
      correction. Polymorphisms of LIG3 were also associated with early onset versus
      late onset depression, whereas the c.-468T>G polymorphism showed the opposite
      association. CONCLUSIONS The SNPs of genes involved in the repair of oxidative
      DNA damage may modulate rDD risk. Since this is an exploratory study, the results
      should to be treated with caution and further work needs to be done to elucidate
      the exact involvement of DNA damage and repair mechanisms in the development of
      this disease.

PMID- 27866213
TI  - Is overlap of respiratory and limb muscle weakness at weaning from mechanical
      ventilation associated with poorer outcomes?

PMID- 27866214
TI  - Vesicouterine fistula: teaching video on diagnosis and surgical treatment.
AB  - INTRODUCTION: A 42-year-old woman presented with urinary incontinence 9 years
      after the last of four vaginal deliveries. She had also had one Caesarean
      section. Immediately after the last delivery, she presented with haematuria,
      which resolved within a few hours, but the drain remained prophylactically for 7
      days. Nine years later, she was referred to a specialist hospital. METHOD: The
      patient presented with continuous urinary incontinence, and physical examination
      revealed a loss of urine from the vagina, the latter confirmed by a methylene
      blue test showing loss of urine from the uterine cervix. Other diagnostic
      techniques used were cystography, cystoscopy and uro-CT. Based on a literature
      review of the management options for such patients and the relevant clinical
      details of our patient, a decision was made to perform a total abdominal
      hysterectomy and fistula repair. RESULTS AND DISCUSSION: Six months following
      surgery, the results were entirely satisfactory, with full urinary continence and
      significant improvement in the patient's quality of life. A discussion about
      controversial approaches to diagnosis and management is included.

PMID- 27866215
TI  - Impact of body mass index on risk of acute kidney injury and mortality in elderly
      patients undergoing hip fracture surgery.
AB  - : The literature is limited regarding risk factors for acute kidney injury (AKI)
      and mortality in hip fracture patients, although AKI is common in these patients.
      While obese patients were at increased risk of AKI, underweight patients with and
      without AKI had elevated mortality for up to 1 year after hip fracture surgery,
      compared with normal-weight patients. INTRODUCTION: This study aimed to examine
      risk of postoperative AKI and subsequent mortality, by body mass index (BMI)
      level, in hip fracture surgery patients aged 65 and over. METHODS: A regional
      cohort study using medical databases was used. We included all patients who
      underwent surgery to repair a hip fracture during the years 2005-2011 (n =
      13,529) at hospitals in Northern Denmark. We calculated cumulative risk of AKI by
      BMI level during 5 days postsurgery and subsequent short-term (6-30 days
      postsurgery) and long-term (31-365 days post-surgery) mortality. We calculated
      crude and adjusted hazard ratios (aHRs) for AKI and death with 95% confidence
      intervals (CIs), comparing underweight, overweight, and obese patients with
      normal-weight patients. RESULTS: Risks of AKI within five postoperative days were
      11.9, 10.1, 12.5, and 17.9% for normal-weight, underweight, overweight, and obese
      patients, respectively. Among those who developed AKI, short-term mortality was
      14.1% for normal-weight patients compared to 23.1% for underweight (aHR 1.7 (95%
      CI 1.2-2.4)), 10.7% for overweight (aHR 0.9 (95% CI 0.6-1.1)), and 15.2% for
      obese (aHR 0.9 (95% CI 0.6-1.4)) patients. Long-term mortality was 24.5% for
      normal-weight, 43.8% for underweight (aHR 1.6 (95% CI 1.0-2.6)), 20.5% for
      overweight (aHR 0.8 (95% CI 0.6-1.2)), and 21.4% for obese (aHR 1.1 (95% CI 0.7
      1.8) AKI patients. Similar associations between BMI and mortality were observed
      among patients without postoperative AKI, although the absolute mortality risk
      estimates by BMI were considerably lower in patients without than in those with
      AKI. CONCLUSIONS: Obese patients were at increased risk of AKI compared with
      normal-weight patients. Among patients with and without postoperative AKI,
      overweight and obesity were not associated with mortality. Compared to normal
      weight patients, underweight patients had elevated mortality for up to 1 year
      after hip fracture surgery irrespective of the presence of AKI. The absolute
      mortality risks were higher in all BMI groups with the presence of AKI.

PMID- 27866217
TI  - Osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF) in an
      osteoporotic patient chronically treated with bisphosphonates.
AB  - The aim of the study is to report the rare association of two complications of
      long-term treatment of osteoporosis with bisphosphonates in the same Caucasian
      elderly patient. A female patient of Italian descent, age 87 years, consulted in
      February 2013. She had a history of osteoporosis and had taken alendronate weekly
      for 7 years (1999-2006). Due to low back pain, an orthopedist had indicated i.v.
      zoledronic acid, 5 mg/year for 3 years (2006-2008). She received occasional
      supplements of ergocalciferol. In 2009, she suffered a fall and sustained a
      subtrochanteric fracture of the left femur. She was operated on and recovered
      uneventfully. In 2012, she consulted a dentist due to loose teeth. She underwent
      the removal of a molar and was given a denture. She had discomfort when using the
      prosthesis, and developed an ulceration in the gum of the mandible, which exposed
      the bone and did not heal for 2 months. After radiologic studies, the diagnosis
      was osteonecrosis of the jaw. She improved after surgical debridement and local
      and systemic antibiotics. In early 2013, laboratory tests were normal except for
      a slight elevation of serum PTH and CTX-I. Calcitriol 0.25 mcg/day was
      prescribed; after 3 months serum calcium, phosphate, PTH, and CTX-I showed no
      variation. Two years later, she experienced acute low back pain after a fall; MRI
      showed recent crushing of D12, and chronic deformities of D11 and L1. Bone
      densitometry of her right hip (DXA) showed a T-score of -2.3 at the femoral neck.
      An X-ray film of the right femur showed diffuse thickening of both cortices. She
      was treated with nasal calcitonin and analgesics. After the back pain subsided,
      she was treated with s.c. denosumab. Although the association of ONJ and AFF was
      known in cancer patients treated with high doses of bisphosphonates, it is very
      rare in patients with osteoporosis receiving these drugs at usual doses. Only
      three cases have been reported, all in oriental women. This appears to be the
      first reported case in a Caucasian woman.

PMID- 27866216
TI  - Association of circulating dipeptidyl-peptidase 4 levels with osteoporotic
      fracture in postmenopausal women.
AB  - : Postmenopausal women with osteoporotic fracture (OF) had higher plasma
      dipeptidyl-peptidase 4 (DPP4) levels than those without. Furthermore, higher
      plasma DPP4 levels were significantly associated with higher bone turnover and a
      higher prevalence of OF. These results indicated that DPP4 may be associated with
      OF by mediating bone turnover rate. INTRODUCTION: Evidence indicates that
      dipeptidyl-peptidase 4 (DPP4) plays a distinct role in bone metabolism. However,
      there has been no report on the association, if any, between circulating DPP4
      levels and osteoporosis-related phenotypes, including osteoporotic fracture (OF).
      Therefore, we performed a case-control study to investigate these associations in
      postmenopausal women. METHODS: This study was conducted in multiple centers in
      Korea. We enrolled 178 cases with OF and 178 age- and body mass index-matched
      controls. OF was assessed by an interviewer-assisted questionnaire and lateral
      thoracolumbar radiographs. Bone turnover markers (BTMs), bone mineral density
      (BMD), and plasma DPP4 levels were obtained in all subjects. RESULTS: After
      adjustment for potential confounders, subjects with OF had significantly higher
      DPP4 levels than those without (P = 0.021). Higher DPP4 levels were significantly
      positively associated with higher levels of all BTMs, but not with BMD at all
      measured sites. The differences in DPP4 levels according to OF status disappeared
      after an additional adjustment for each BTM, but not after adjustment for any BMD
      values. BTMs explained approximately half of the relationship between DPP4 and
      OF. The risk of OF was 3.80-fold (95% confidence interval = 1.53-9.42) higher in
      subjects in the highest DPP4 quartile than in those in the lowest quartile after
      adjustment for potential confounders, including femoral neck BMD. CONCLUSIONS:
      DPP4 may be associated with OF by at least partly mediating the bone turnover
      rate. Circulating DPP4 levels may be a potential biomarker that could increase
      the predictive power of current fracture risk assessment models.

PMID- 27866218
TI  - Prevalence of negative CT scans in a level one trauma center.
AB  - PURPOSE: The rise of computed tomography (CT) use in trauma has become the
      subject of concern given the harms of CT including radiation, cost, over
      diagnosis and identification of incidental lesions. We developed a novel metric,
      the Negative CT Score, (?CT-) which quantifies how often CT imaging identifies
      important injuries. Our objective was to describe the pattern of CT utilization
      in trauma at an urban academic level one trauma center using this novel metric.
      METHODS: This was a retrospective study of intermediate level trauma patients who
      received CT imaging over a 1-year study period at an urban level one trauma
      center. We applied the Negative CT Score, (?CT-) to quantify the results of CT
      imaging. ?CT- is computed by subtracting the number of non-extremity body regions
      (maximum four: head, neck, chest, abdomen) with an important positive CT finding
      (defined by a priori criteria) from the total number of non-extremity body
      regions scanned. RESULTS: Of the 552 cases reviewed during the study period, 410
      (74.3%) were male and the mean age was 40.3 years [SD +/- 21.2]. Four hundred
      eighty-six patients (88.0%) suffered blunt trauma; 66 (12.0%) suffered
      penetrating trauma. The average injury severity score for admitted patients was
      seven. Four hundred ninety-five cases had at least one CT performed. The average
      number of regions per patient that received CT imaging was 2.36 (SD +/- 1.3), and
      the average ?CT- was 2.10 (SD +/- 1.2). Three hundred and sixty-seven (74.3%)
      patients had no important findings on CT imaging. CONCLUSIONS: In a consecutive
      series of 552 intermediate trauma patients at our urban trauma center, 2.36 body
      regions were scanned per patient; of these, 2.10 regions revealed no important CT
      findings. We hope that these results and the Negative CT Score can be used to
      identify trends, variations in practice, and outliers within and across
      departments so that CT utilization can be optimized.

PMID- 27866219
TI  - Mental health of children who work on the streets in Brazil after enrollment in a
      psychosocial program.
AB  - PURPOSE: To evaluate the mental health status of children working on the streets
      in Sao Paulo City, Brazil, two years after their participation in a psychosocial
      program, and to identify factors associated with their mental health status.
      METHODS: From a total sample of 126 children working on the streets, 107 (85%)
      were re-evaluated two years after the initiation of a psychosocial program which
      aimed to cease their work on the streets. The focus was the presence of mental
      health problems, defined based on a screening instrument (Strengths and
      Difficulties Questionnaire). Logistic regression models tested factors related to
      the probability that a child would not present mental health problems at follow
      up. RESULTS: The likelihood of a child presenting mental health problems was
      higher at baseline compared to the two-year follow-up (67.5 and 56.1%,
      respectively). Absence of mental health problems two years after a psychosocial
      intervention was significantly correlated with the following baseline factors:
      lower level of caregiver's psychiatric symptoms as measured by the SRQ (Self
      Report Questionnaire) (AOR = 0.84, p = 0.0065), absence of child physical neglect
      (AOR = 0.38, p = 0.0705) and parental Protestant religion affiliation, compared
      to other religions (AOR = 4.06; p = 0.0107). CONCLUSIONS: Different factors are
      related to the absence of mental health problems of children working on the
      streets after enrollment in a two-year psychosocial program. Our findings suggest
      that interventions that aim to improve child mental health should consider the
      detection of psychiatric symptoms in caregivers, provide treatment when it is
      needed, and also assess other problems such as neglect in the family setting.

PMID- 27866222
TI  - The cytoskeletal protein septin 11 is associated with human obesity and is
      involved in adipocyte lipid storage and metabolism.
AB  - AIMS/HYPOTHESIS: Septins are newly identified members of the cytoskeleton that
      have been proposed as biomarkers of a number of diseases. However, septins have
      not been characterised in adipose tissue and their relationship with obesity and
      insulin resistance remains unknown. Herein, we characterised a member of this
      family, septin 11 (SEPT11), in human adipose tissue and analysed its potential
      involvement in the regulation of adipocyte metabolism. METHODS: Gene and protein
      expression levels of SEPT11 were analysed in human adipose tissue. SEPT11
      distribution was evaluated by immunocytochemistry, electron microscopy and
      subcellular fractionation techniques. Glutathione S-transferase (GST) pull-down,
      immunoprecipitation and yeast two-hybrid screening were used to identify the
      SEPT11 interactome. Gene silencing was used to assess the role of SEPT11 in the
      regulation of insulin signalling and lipid metabolism in adipocytes. RESULTS: We
      demonstrate the expression of SEPT11 in human adipocytes and its upregulation in
      obese individuals, with SEPT11 mRNA content positively correlating with variables
      of insulin resistance in subcutaneous adipose tissue. SEPT11 content was
      regulated by lipogenic, lipolytic and proinflammatory stimuli in human
      adipocytes. SEPT11 associated with caveolae in mature adipocytes and interacted
      with both caveolin-1 and the intracellular fatty acid chaperone, fatty acid
      binding protein 5 (FABP5). Lipid loading of adipocytes caused the association of
      the three proteins with the surface of lipid droplets. SEPT11 silencing impaired
      insulin signalling and insulin-induced lipid accumulation in adipocytes.
      CONCLUSIONS/INTERPRETATION: Our findings support a role for SEPT11 in lipid
      traffic and metabolism in adipocytes and open new avenues for research on the
      control of lipid storage in obesity and insulin resistance.

PMID- 27866223
TI  - Circulating microRNA levels predict residual beta cell function and glycaemic
      control in children with type 1 diabetes mellitus.
AB  - AIMS/HYPOTHESIS: We aimed to identify circulating microRNA (miRNA) that predicts
      clinical progression in a cohort of 123 children with new-onset type 1 diabetes
      mellitus. METHODS: Plasma samples were prospectively obtained at 1, 3, 6, 12 and
      60 months after diagnosis from a subset of 40 children from the Danish Remission
      Phase Cohort, and profiled for miRNAs. At the same time points, meal-stimulated C
      peptide and HbA1c levels were measured and insulin-dose adjusted HbA1c (IDAA1c)
      calculated. miRNAs that at 3 months after diagnosis predicted residual beta cell
      function and glycaemic control in this subgroup were further validated in the
      remaining cohort (n = 83). Statistical analysis of miRNA prediction for disease
      progression was performed by multiple linear regression analysis adjusted for age
      and sex. RESULTS: In the discovery analysis, six miRNAs (hsa-miR-24-3p, hsa-miR
      146a-5p, hsa-miR-194-5p, hsa-miR-197-3p, hsa-miR-301a-3p and hsa-miR-375) at 3
      months correlated with residual beta cell function 6-12 months after diagnosis.
      Stimulated C-peptide at 12 months was predicted by hsa-miR-197-3p at 3 months (p
      = 0.034). A doubling of this miRNA level corresponded to a sixfold higher
      stimulated C-peptide level. In addition, a doubling of hsa-miR-24-3p and hsa-miR
      146a-5p levels at 3 months corresponded to a 4.2% (p < 0.014) and 3.5% (p <
      0.022) lower IDAA1c value at 12 months. Analysis of the remaining cohort
      confirmed the initial finding for hsa-miR-197-3p (p = 0.018). The target genes
      for the six miRNAs revealed significant enrichment for pathways related to
      gonadotropin-releasing hormone receptor and angiogenesis pathways.
      CONCLUSIONS/INTERPRETATION: The miRNA hsa-miR-197-3p at 3 months was the
      strongest predictor of residual beta cell function 1 year after diagnosis in
      children with type 1 diabetes mellitus.

PMID- 27866221
TI  - Inter-organ regulation of adipose tissue browning.
AB  - Adaptive thermogenesis is an important component of energy expenditure. Brown
      adipocytes are best known for their ability to convert chemical energy into heat.
      Beige cells are brown-like adipocytes that arise in white adipose tissue in
      response to certain environmental cues to dissipate heat and improve metabolic
      homeostasis. A large body of intrinsic factors and external signals are critical
      for the function of beige adipocytes. In this review, we discuss recent advances
      in our understanding of neuronal, hormonal, and metabolic regulation of the
      development and activation of beige adipocytes, with a focus on the regulation of
      beige adipocytes by other organs, tissues, and cells. Understanding the cellular
      and molecular mechanisms of inter-organ regulation of adipose tissue browning may
      provide an avenue for combating obesity and associated diseases.

PMID- 27866225
TI  - Characterization of a common wheat (Triticum aestivum L.) high-tillering dwarf
      mutant.
AB  - KEY MESSAGE: A novel high-tillering dwarf mutant in common wheat Wangshuibai was
      characterized and mapped to facilitate breeding for plant height and tiller and
      the future cloning of the causal gene. Tiller number and plant height are two
      major agronomic traits in cereal crops affecting plant architecture and grain
      yield. NAUH167, a mutant of common wheat landrace Wangshuibai induced by
      ethylmethyl sulfide (EMS) treatment, exhibits higher tiller number and reduced
      plant height. Microscope observation showed that the dwarf phenotype was
      attributed to the decrease in the number of cells and their length. The same as
      the wild type, the mutant was sensitive to exogenous gibberellins. Genetic
      analysis showed that the high-tillering number and dwarf phenotype were related
      and controlled by a partial recessive gene. Using a RIL2:6 population derived
      from the cross NAUH167/Sumai3, a molecular marker-based genetic map was
      constructed. The map consisted of 283 loci, spanning a total length of 1007.98 cM
      with an average markers interval of 3.56 cM. By composite interval mapping, a
      stable major QTL designated QHt.nau-2D controlling both traits, was mapped to the
      short arm of chromosome 2D flanked by markers Xcfd11 and Xgpw361. To further map
      the QHt.nau-2D loci, another population consisted of 180 F2 progeny from a cross
      2011I-78/NAUH167 was constructed. Finally, QHt.nau-2D was located within a
      genetic region of 0.8 cM between markers QHT239 and QHT187 covering a predicted
      physical distance of 6.77 Mb. This research laid the foundation for map-based
      cloning of QHt.nau-2D and would facilitate the characterization of plant height
      and tiller number in wheat.

PMID- 27866226
TI  - High accuracy of predicting hybrid performance of Fusarium head blight resistance
      by mid-parent values in wheat.
AB  - KEY MESSAGE: Mid-parent values of Fusarium head blight (FHB) resistance tested
      across several locations are a good predictor of hybrid performance caused by a
      preponderance of additive gene action in wheat. Hybrid breeding is intensively
      discussed as one solution to boost yield and yield stability including an
      enhanced biotic stress resistance. Our objectives were to investigate (1) the
      heterosis for Fusarium head blight (FHB) resistance, (2) the importance of
      general (GCA) vs. specific combining ability (SCA) for FHB resistance, and (3)
      the possibility to predict the FHB resistance of the hybrids by the parental
      means. We re-analyzed phenotypic data of a large population comprising 1604
      hybrids and their 120 female and 15 male parental lines evaluated in inoculation
      trials across seven environments. Mid-parent heterosis of FHB severity averaged 
      9%, with a range from -36 to +35%. Mean better parent heterosis was 2% and 78 of
      the hybrids significantly (P < 0.05) outperformed the best commercial check
      variety included in our study. FHB resistance was not correlated with grain yield
      in healthy status for lines (r = 0.01) and hybrids (r = 0.09, P < 0.01). While a
      preponderance of GCA variance (P < 0.01) was found, SCA variance was not
      significantly different from zero. Accuracy to predict hybrid performance of FHB
      severity based on mid-parent values and on GCA effects was high (r = 0.70 and
      0.86, respectively; P < 0.01). Similarly, line per se performance and GCA effects
      were significantly correlated (r = 0.77; P < 0.01). The substantial level of mid
      parent heterosis in the desired direction of decreased susceptibility and the
      negligible better parent heterosis suggest that hybrids are an attractive
      alternative variety type to improve FHB resistance.

PMID- 27866224
TI  - The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis
      in ApoE -/- mice fed a western diet.
AB  - AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a
      lower rate of cardiovascular and all-cause mortality when compared with placebo
      in patients with type 2 diabetes. We investigated the effect of empagliflozin
      (compared with glimepiride) on the progression of atherosclerosis, and its
      possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE -/- mice
      were fed a western diet for 20 weeks and divided into four groups: control
      (saline, 154 mmol/l NaCl), glimepiride 0.1 mg/kg, empagliflozin 1 mg/kg and
      empagliflozin 3 mg/kg (n = 12/group). Plaque size and composition in the aortic
      arch/valve areas and cardiovascular risk variables in the blood and tissues were
      evaluated. Insulin resistance was estimated by HOMA and adiponectin levels. Body
      composition was determined using dual-energy x-ray absorptiometry. RESULTS: After
      8 weeks of treatment, the empagliflozin and glimepiride groups exhibited
      decreased blood glucose levels. Atherosclerotic plaque areas in the aortic
      arch/valve were significantly smaller in the empagliflozin groups than in the
      control or glimepiride groups. Insulin resistance and circulating concentrations
      of TNF-alpha, IL-6, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A
      and urinary microalbumin decreased after empagliflozin treatment, and this
      significantly correlated with plaque size. Empagliflozin treatment reduced weight
      and fat mass, lipid droplets in the liver, fat cell size, mRNA expression of Tnf,
      Il6 and Mcp-1 (also known as Ccl2) and the infiltration of inflammatory cells in
      plaque and adipose tissue compared with the control or glimepiride group.
      Empagliflozin treatment increased adiponectin levels. CONCLUSIONS/INTERPRETATION:
      Improvements in inflammation and insulin resistance seem to be mechanisms
      involved in the mitigation of atherosclerosis by empagliflozin.

PMID- 27866227
TI  - Genome-wide association mapping of resistance to eyespot disease
      (Pseudocercosporella herpotrichoides) in European winter wheat (Triticum aestivum
      L.) and fine-mapping of Pch1.
AB  - KEY MESSAGE: Genotypes with recombination events in the Triticum ventricosum
      introgression on chromosome 7D allowed to fine-map resistance gene Pch1, the main
      source of eyespot resistance in European winter wheat cultivars. Eyespot (also
      called Strawbreaker) is a common and serious fungal disease of winter wheat
      caused by the necrotrophic fungi Oculimacula yallundae and Oculimacula acuformis
      (former name Pseudocercosporella herpotrichoides). A genome-wide association
      study (GWAS) for eyespot was performed with 732 microsatellite markers (SSR) and
      7761 mapped SNP markers derived from the 90 K iSELECT wheat array using a panel
      of 168 European winter wheat varieties as well as three spring wheat varieties
      and phenotypic evaluation of eyespot in field tests in three environments. Best
      linear unbiased estimations (BLUEs) were calculated across all trials and ranged
      from 1.20 (most resistant) to 5.73 (most susceptible) with an average value of
      4.24 and a heritability of H 2 = 0.91. A total of 108 SSR and 235 SNP marker
      trait associations (MTAs) were identified by considering associations with a 
      log10 (P value) >=3.0. Significant MTAs for eyespot-score BLUEs were found on
      chromosomes 1D, 2A, 2D, 3D, 5A, 5D, 6A, 7A and 7D for the SSR markers and
      chromosomes 1B, 2A, 2B, 2D, 3B and 7D for the SNP markers. For 18 varieties
      (10.5%), a highly resistant phenotype was detected that was linked to the
      presence of the resistance gene Pch1 on chromosome 7D. The identification of
      genotypes with recombination events in the introgressed genomic segment from
      Triticum ventricosum harboring the Pch1 resistance gene on chromosome 7DL allowed
      the fine-mapping of this gene using additional SNP markers and a potential
      candidate gene Traes_7DL_973A33763 coding for a CC-NBS-LRR class protein was
      identified.

PMID- 27866220
TI  - Molecular basis of mycobacterial survival in macrophages.
AB  - Macrophages play an essential role in the immune system by ingesting and
      degrading invading pathogens, initiating an inflammatory response and instructing
      adaptive immune cells, and resolving inflammation to restore homeostasis. More
      interesting is the fact that some bacteria have evolved to use macrophages as a
      natural habitat and tools of spread in the host, e.g., Mycobacterium tuberculosis
      (Mtb) and some non-tuberculous mycobacteria (NTM). Mtb is considered one of
      humanity's most successful pathogens and is the causal agent of tuberculosis,
      while NTMs cause opportunistic infections all of which are of significant public
      health concern. Here, we describe mechanisms by which intracellular pathogens,
      with an emphasis on mycobacteria, manipulate macrophage functions to circumvent
      killing and live inside these cells even under considerable immunological
      pressure. Such macrophage functions include the selective evasion or engagement
      of pattern recognition receptors, production of cytokines, reactive oxygen and
      nitrogen species, phagosome maturation, as well as other killing mechanisms like
      autophagy and cell death. A clear understanding of host responses elicited by a
      specific pathogen and strategies employed by the microbe to evade or exploit
      these is of significant importance for the development of effective vaccines and
      targeted immunotherapy against persistent intracellular infections like
      tuberculosis.

PMID- 27866228
TI  - Fine mapping of the chromosome 5B region carrying closely linked rust resistance
      genes Yr47 and Lr52 in wheat.
AB  - KEY MESSAGE: Fine mapping of Yr47 and Lr52 in chromosome arm 5BS of wheat
      identified close linkage of the marker sun180 to both genes and its robustness
      for marker-assisted selection was demonstrated. The widely effective and
      genetically linked rust resistance genes Yr47 and Lr52 have previously been
      mapped in the short arm of chromosome 5B in two F3 populations (Aus28183/Aus27229
      and Aus28187/Aus27229). The Aus28183/Aus27229 F3 population was advanced to
      generate an F6 recombinant inbred line (RIL) population to identify markers
      closely linked with Yr47 and Lr52. Diverse genomic resources including flow
      sorted chromosome survey sequence contigs representing the orthologous region in
      Brachypodium distachyon, the physical map of chromosome arm 5BS, expressed
      sequence tags (ESTs) located in the 5BS6-0.81-1.00 deletion bin and resistance
      gene analog contigs of chromosome arm 5BS were used to develop markers to
      saturate the target region. Selective genotyping was also performed using the
      iSelect 90 K Infinium wheat SNP assay. A set of SSR, STS, gene-based and SNP
      markers were developed and genotyped on the Aus28183/Aus27229 RIL population.
      Yr47 and Lr52 are genetically distinct genes that mapped 0.4 cM apart in the RIL
      population. The SSR marker sun180 co-segregated with Lr52 and mapped 0.4 cM
      distal to Yr47. In a high resolution mapping population of 600 F2 genotypes Yr47
      and Lr52 mapped 0.2 cM apart and marker sun180 was placed 0.4 cM distal to Lr52.
      The amplification of a different sun180 amplicon (195 bp) than that linked with
      Yr47 and Lr52 (200 bp) in 204 diverse wheat genotypes demonstrated its robustness
      for marker-assisted selection of these genes.

PMID- 27866229
TI  - Vascular epiphytes and host trees of ant-gardens in an anthropic landscape in
      southeastern Mexico.
AB  - Ant-gardens (AGs) are considered one of the most complex mutualist systems
      between ants and plants, since interactions involving dispersal, protection, and
      nutrition occur simultaneously in them; however, little is known about the
      effects of the transformation of ecosystems on their diversity and interactions.
      In five environments with different land use within an anthropic landscape in
      southeastern Mexico, we investigated the diversity and composition of epiphytes
      and host trees of AGs built by Azteca gnava. A total of 10,871 individuals of 26
      epiphytic species, associating with 859 AGs located in 161 host trees, were
      recorded. The diversity and composition of epiphytes tended to be different
      between environments; however, Aechmea tillandsioides and Codonanthe uleana were
      the most important species and considered true AG epiphytes, because they were
      the most frequent, abundant, and occurred exclusively in AGs. Other important
      species were the orchids Epidendrum flexuosum, Coryanthes picturata, and
      Epidendrum pachyrachis, and should also be considered true AG epiphytes, because
      they occurred almost exclusively in the AGs. The AG abundance in agroforestry
      plantations was similar or even greater than in riparian vegetation (natural
      habitat). The AGs were registered in 37 host species but were more frequent in
      Mangifera indica and Citrus sinensis. We conclude that true epiphytes of A. gnava
      AGs persist in different environments and host trees, and even these AGs could
      proliferate in agroforestry plantations of anthropic landscapes.

PMID- 27866232
TI  - Surgical treatment of two adolescent athletes with dislocated avulsion fracture
      of the anterior superior iliac spine (ASIS).
AB  - INTRODUCTION: Avulsion fractures of the anterior superior iliac spine are rare.
      Therefore, evidence-based treatment guidelines do not exist. The therapeutic
      options are either conservative treatment or surgical intervention. The decision
      depends on grade of dislocation, age of the patient, and his sportive demands and
      competitive requirements. MATERIALS AND METHODS: We present the cases of two
      young athletes suffering from traumatic avulsion fractures of the anterior
      superior iliac spine. In both cases, the musculotendinous unit (sartorius muscle
      and tensor of the fascia lata) remained attached to the loose dislocated
      fragment. Both patients were treated by means of open reduction with a new
      surgical technique using suture anchors. RESULTS: Both patients were pain-free 4
      weeks after surgery and had full range of motion. They were able to return to
      their preoperative sportive activity levels 10 weeks after surgery. No
      complications were reported at final follow-up 18 months postoperatively.
      CONCLUSION: Operative treatment of avulsion fracture of the ASIS using suture
      anchors shows excellent clinical outcome and a short convalescence period. The
      patients achieve their preinjury sportive levels within 3 months.

PMID- 27866231
TI  - Presynaptic proteins complexin-I and complexin-II differentially influence
      cognitive function in early and late stages of Alzheimer's disease.
AB  - Progressive accumulation of Alzheimer's disease-related pathology is associated
      with cognitive dysfunction. Differences in cognitive reserve may contribute to
      individual differences in cognitive function in the presence of comparable
      neuropathology. The protective effects of cognitive reserve could contribute
      differentially in early versus late stages of the disease. We investigated
      presynaptic proteins as measures of brain reserve (a subset of total cognitive
      reserve), and used Braak staging to estimate the progression of Alzheimer's
      disease. Antemortem evaluations of cognitive function, postmortem assessments of
      pathologic indices, and presynaptic protein analyses, including the complexins I
      and II as respective measures of inhibitory and excitatory terminal function,
      were assayed in multiple key brain regions in 418 deceased participants from a
      community study. After covarying for demographic variables, pathologic indices,
      and overall synapse density, lower brain complexin-I and -II levels contributed
      to cognitive dysfunction (P < 0.01). Each complexin appeared to be dysregulated
      at a different Braak stage. Inhibitory complexin-I explained 14.4% of the
      variance in global cognition in Braak 0-II, while excitatory complexin-II
      explained 7.3% of the variance in Braak V-VI. Unlike other presynaptic proteins,
      complexins did not colocalize with pathologic tau within neuritic plaques,
      suggesting that these functional components of the synaptic machinery are cleared
      early from dystrophic neurites. Moreover, complexin levels showed distinct
      patterns of change related to memory challenges in a rat model, supporting the
      functional specificity of these proteins. The present results suggest that
      disruption of inhibitory synaptic terminals may trigger early cognitive
      impairment, while excitatory terminal disruption may contribute relatively more
      to later cognitive impairment.

PMID- 27866230
TI  - Differential expression and emerging functions of non-coding RNAs in cold
      adaptation.
AB  - Several species undergo substantial physiological and biochemical changes to
      confront the harsh conditions associated with winter. Small mammalian hibernators
      and cold-hardy insects are examples of natural models of cold adaptation that
      have been amply explored. While the molecular picture associated with cold
      adaptation has started to become clearer in recent years, notably through the use
      of high-throughput experimental approaches, the underlying cold-associated
      functions attributed to several non-coding RNAs, including microRNAs (miRNAs) and
      long non-coding RNAs (lncRNAs), remain to be better characterized. Nevertheless,
      key pioneering work has provided clues on the likely relevance of these molecules
      in cold adaptation. With an emphasis on mammalian hibernation and insect cold
      hardiness, this work first reviews various molecular changes documented so far in
      these processes. The cascades leading to miRNA and lncRNA production as well as
      the mechanisms of action of these non-coding RNAs are subsequently described.
      Finally, we present examples of differentially expressed non-coding RNAs in
      models of cold adaptation and elaborate on the potential significance of this
      modulation with respect to low-temperature adaptation.

PMID- 27866234
TI  - The RNA World at Thirty: A Look Back with its Author.
AB  - Thirty years ago, molecular biologist Walter Gilbert published his RNA world
      hypothesis, which posited that early in evolution living systems were composed
      entirely of RNA. Proposed in the immediate wake of the discovery that certain RNA
      molecules were capable of catalyzing biological reactions, the hypothesis
      ascribed both of life's essential functions, namely carrying information and
      catalysis-respectively, performed by DNA and proteins in most modern life systems
      to RNA, which were labeled as ribozymes. In the years since its inception, the
      RNA world has been greeted with equal parts enthusiasm and opposition from the
      origins of life research community, of which Gilbert neither was, nor really
      became, a part. For this special historical issue of the Journal of Molecular
      Evolution, Gilbert agreed to revisit his hypothesis and share his memories about
      the theory's origins and his insights into its fate in the years since he first
      published his idea.

PMID- 27866233
TI  - A Treatise to Computational Approaches Towards Prediction of Membrane Protein and
      Its Subtypes.
AB  - Membrane proteins are vital mediating molecules responsible for the interaction
      of a cell with its surroundings. These proteins are involved in different
      functionalities such as ferrying of molecules and nutrients across membrane,
      recognizing foreign bodies, receiving outside signals and translating them into
      the cell. Membrane proteins play significant role in drug interaction as nearly
      50% of the drug targets are membrane proteins. Due to the momentous role of
      membrane protein in cell activity, computational models able to predict membrane
      protein with accurate measures bears indispensable importance. The conventional
      experimental methods used for annotating membrane proteins are time-consuming and
      costly and in some cases impossible. Computationally intelligent techniques have
      emerged to be as a useful resource in the automation of prediction and hence the
      annotation process. In this study, various techniques have been reviewed that are
      based on different computational intelligence models used for prediction process.
      These techniques were formulated by different researchers and were further
      evaluated to provide a comparative analysis. Analysis shows that the usage of
      support vector machine-based prediction techniques bears more assiduous results.

PMID- 27866236
TI  - Effects of Physical Exercise on Markers of Cellular Immunosenescence: A
      Systematic Review.
AB  - Aging affects negatively the immune system, defined as immunosenescence, which
      increases the susceptibility of elderly persons to infection, autoimmune disease,
      and cancer. There are strong indications that physical exercise in elderly
      persons may prevent the age-related decline in immune response without
      significant side effects. Consequently, exercise is being considered as a safe
      mode of intervention to reduce immunosenescence. The aim of this review was to
      appraise the existing evidence regarding the impact of exercise on surface
      markers of cellular immunosenescence in either young and old humans or animals.
      PubMed and Web of Science were systematically screened, and 28 relevant articles
      in humans or animals were retrieved. Most of the intervention studies
      demonstrated that an acute bout of exercise induced increases in senescent,
      naive, memory CD4+ and CD8+ T-lymphocytes and significantly elevated apoptotic
      lymphocytes in peripheral blood. As regards long-term effects, exercise induced
      increased levels of T-lymphocytes expressing CD28+ in both young and elderly
      subjects. Few studies found an increase in natural killer cell activity following
      a period of training. We can conclude that exercise has considerable effects on
      markers of cellular aspects of the immune system. However, very few studies have
      been conducted so far to investigate the effects of exercise on markers of
      cellular immunosenescence in elderly persons. Implications for immunosenescence
      need further investigation.

PMID- 27866235
TI  - Arthroscopically-assisted mini open partial synovectomy for the treatment of
      localized pigmented villonodular synovitis of the knee. A retrospective
      comparative study with long-term follow up.
AB  - PURPOSE: The purpose of this study was to present the long-term results of
      treatment of localized pigmented villonodular synovitis (LPVNS) comparing two
      operative procedures of excision of the lesion-the arthroscopic and the
      arthroscopically assisted mini-open. We hypothesized that the latter approach
      allowed for treatment of LPVNS with acceptable recurrence rates, complication
      rates and functional outcomes. METHODS: Between 1990 and 2006, 21 patients with
      LPVNS were treated with partial synovectomy through an arthroscopically-assisted
      mini open technique (group A), and 23 patients were treated with an arthroscopic
      excision of the lesion (group B). All patients were clinically examined at one,
      three, and 12 months post-operatively and graded by the Lysholm knee score and
      the Ogilvie-Harris score. RESULTS: The mean Lysholm score was improved from 58.7
      +/- 9 to 94.2 +/- 7 for group A (p < 0.05) and from 57.4 +/- 9.1 to 95.5 +/- 8
      for group B (p < 0.05). The mean Ogilvie-Harris score was improved from 7.2 +/- 2
      to 11.2 +/- 0.9 for group A and from 7.1 +/- 2 to 11.75 +/- 0.5 for group B (p <
      0.05). We encountered two cases of CRPS and one case of recurrence of the lesion
      in group A and no complications for group B. CONCLUSIONS: Arthroscopically
      assisted mini open partial synovectomy is a safe alternative treatment,
      especially for surgeons without extended experience in arthroscopic techniques.
      The arthroscopic localization of the precise position of the lesion and its
      subsequent mini-open excision is a safe and effective technique with very low
      morbidity and recurrence rate and equivalent functional outcome to fully
      arthroscopic excision due to limited incision. LEVEL OF EVIDENCE: Retrospective
      comparative study, Level III.

PMID- 27866238
TI  - Topological horseshoe and its uniform hyperbolicity in the HP model.
AB  - A famous food-chain model proposed by Hastings and Powell is numerically
      restudied. The existence and uniform hyperbolicity of chaotic invariant sets are
      demonstrated by means of the topological horseshoe theory and the Conley-Moser
      conditions, indicating that, for a fixed cross section, the second return
      Poincare map of the model possesses a closed uniformly hyperbolic chaotic
      invariant set, on which it is topologically conjugate to the 2-shift map.

PMID- 27866239
TI  - Diffusion kurtosis imaging and diffusion-weighted imaging in assessment of liver
      fibrosis stage and necroinflammatory activity.
AB  - PURPOSE: To investigate and compare the diagnostic value of diffusion kurtosis
      imaging (DKI) with diffusion-weighted imaging (DWI) in assessing and quantifying
      hepatic fibrosis. METHODS: Thirty rats were divided into the control group (n =
      6) and the fibrosis experimental groups (n = 6 per group) with CCl4
      administration for 2, 4, 6, and 8 weeks. Liver fibrosis stage (S) and
      necroinflammatory activity grade (G) were histopathologically determined. DKI and
      DWI were performed; mean apparent diffusion (MD), mean kurtosis (MK), and
      apparent diffusion coefficient (ADC) values were calculated. DKI parameters were
      compared with ADC values according to G/S scores. RESULTS: Strong inverse
      correlations were found between the degree of fibrosis and both MD and ADC (r = 
      0.840 and r = -0.760), while only weak correlation existed in MK (r = 0.405). ROC
      analyses demonstrated the AUC in MD, MK, and ADC of 0.862, 0.684, 0.817 for
      identifying mild and severe fibrosis, and 0.757, 0.675, 0.733 for non-cirrhosis
      and cirrhosis, respectively. The degree of fibrosis was significantly correlated
      with alpha-smooth muscle actin (alpha-SMA) (P < 0.0001); alpha-SMA had strong
      inverse correlation with MD (r = -0.723), moderate inverse correlation with ADC
      (r = -0.613), and very weak correlation with MK (r = 0.175). Additionally, MD was
      strongly correlated with the necroinflammatory activity (r = -0.758), ADC was
      moderately correlated (r = -0.492), and MK was weakly correlated (r = 0.254).
      CONCLUSION: DKI may provide added information and serve as a valuable tool for
      the characterization and surveillance of liver fibrosis in a non-invasive manner.

PMID- 27866237
TI  - Long-Term Effects of Intravenous Ibandronate in Paget's Disease of Bone.
AB  - We have previously demonstrated that intravenous ibandronate produces high
      initial response rates in Paget's disease, but the durability of this effect is
      unknown. It might be expected to be short lived because ibandronate has a low
      affinity for bone. Here we report long-term follow-up (up to 14 years) of
      patients from that trial. Twenty-five patients with active Paget's disease
      [baseline serum total alkaline phosphatase (ALP) ~3 times the upper limit of
      normal] received either 6 or 12 mg intravenous ibandronate at baseline. There
      were prompt reductions in ALP following treatment, with normalization in 88%. ALP
      remained in the normal range in most patients for 20-30 months, but some subjects
      then showed gradual increases. Three years after ibandronate, before any patients
      had received additional treatment, ALP was normal in 61%. Six patients maintained
      normal ALP beyond 6 years without further intervention. Responses to 6 and 12 mg
      were similar. These results indicate that long-term remissions in Paget's disease
      can be achieved with bolus delivery of a potent bisphosphonate, even if the drug
      has a low affinity for bone. Therefore, bisphosphonate retention in bone might
      not be the only factor determining duration of remission. Intravenous
      bisphosphonates are likely to produce high drug concentrations within pagetic
      lesions which might result in cytotoxicity to the pagetic cells, leading to long
      durations of remission. These findings strengthen the evidence that potent
      bisphosphonates delivered in a single intravenous dose are a very efficient way
      to manage this condition.

PMID- 27866240
TI  - Extranodal lymphomas of abdomen and pelvis: imaging findings and differential
      diagnosis.
AB  - A wide spectrum of extranodal lymphomas in the abdomen and pelvis is commonly
      encountered by imaging. Diagnosing these lesions generally requires a
      multimodality approach. This review highlights imaging appearances of extranodal
      lymphomas in the abdomen and pelvis with emphasis on computed tomography,
      magnetic resonance imaging, and positron emission tomography-computed tomography
      along with the relevant differential diagnosis.

PMID- 27866241
TI  - Elevated regulatory T cells, surface and intracellular CTLA-4 expression and
      interleukin-17 in the lung cancer microenvironment in humans.
AB  - Regulatory T cells (Tregs) play an important role in the suppression of the
      immune response in lung cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4)
      expressed on T lymphocytes is capable of downregulating cytotoxic T cells and is
      constitutively expressed on Tregs. Little is known about the population of Tregs
      with two forms of CTLA-4: surface (s) and intracellular (in) in the lung cancer
      environment. Th17 cells defined by production of IL-17 have pleiotropic functions
      in anticancer immune response. Our aim was to detect the elements of immune
      response regulation in lung cancer in three compartments: by analysis of
      bronchoalveolar lavage fluid (BALF) from the lung affected by cancer (clBALF),
      healthy symmetrical lung (hlBALF) and peripheral blood (PB) from the same
      patient. A total of 54 samples were collected. Tregs, (s)CTLA-4, (in)CTLA-4 were
      detected by flow cytometry with antibodies against CD4, CD25, Foxp3, CD127, CTLA
      4, and concentration of IL-17 was estimated by ELISA. We observed a significantly
      higher proportion of Tregs in clBALF than in hlBALF or PB (8.5 vs. 5.0 vs. 5.1%,
      respectively, p < 0.05). The median proportion of (in)CTLA-4+ Tregs was higher in
      clBALF than in hlBALF or PB (89.0, 81.5, 56.0%, p < 0.05). IL-17 concentration
      was the highest in clBALF-6.6 pg/ml. We observed a significant correlation
      between the proportion of Tregs and (in)CTLA-4+ Tregs with IL-17A concentration
      in clBALF. We confirmed significant differences in the proportion of regulatory
      elements between cancerous lung and healthy lung and PB and the usefulness of
      BALF analysis in evaluation of immune response regulation in local lung cancer
      environment.

PMID- 27866242
TI  - Elevated systemic interleukin-7 in patients with colorectal cancer and
      individuals at high risk of cancer: association with lymph node involvement and
      tumor location in the right colon.
AB  - Interleukin (IL)-7 is a cytokine essential for protective immunity, and it is
      considered as a promising agent for cancer immunotherapy. Recent studies,
      however, appear to associate IL-7 with aggressiveness of solid tumors. The IL-7
      has been less studied in colorectal cancer (CRC) and conditions associated with
      increased risk of CRC development. To explore IL-7 status in bowel diseases, it
      was measured immunofluorometrically in 431 individuals (110 with CRC) by using
      Luminex platform. A level of IL-7 in CRC patients was significantly higher than
      in controls, did not differ from those with adenomas, but was lower than in both
      active and inactive inflammatory bowel disease (IBD) cases. In CRC, IL-7 was
      higher in patients with lymph node and distant metastases and with tumors located
      in right colon. In adenomas, IL-7 elevation was associated exclusively with
      villous growth pattern, while in IBD, circulating IL-7 reflected clinical
      activity of Crohn's disease and ulcerative colitis. Systemic TNFalpha, IL-10, and
      PDGF-BB were independent predictors of circulating IL-7. In summary, our study is
      the first to demonstrate IL-7 elevation in CRC in association with metastatic
      disease and tumor location. Both associations should be considered when designing
      IL-7-based immunotherapies for CRC. Further studies on IL-7 functionality in CRC
      are necessary.

PMID- 27866243
TI  - Monitoring of adherence to headache treatments by means of hair analysis.
AB  - PURPOSE: The aim of this study was to evaluate the potential of hair analysis to
      monitor medication adherence in headache patients undergoing chronic therapy. For
      this purpose, the following parameters were analyzed: the detection rate of 23
      therapeutic drugs in headache patients' hair, the degree of agreement between the
      self-reported drug and the drug found in hair, and whether the levels found in
      hair reflected the drug intake reported by the patients. METHODS: The study
      included 93 patients suffering from primary headaches declaring their daily
      intake of at least one of the following drugs during the 3 months before the hair
      sampling: alprazolam, amitriptyline, citalopram, clomipramine, clonazepam,
      delorazepam, diazepam, duloxetine, fluoxetine, flurazepam, levomepromazine,
      levosulpiride, lorazepam, lormetazepam, mirtazapine, paroxetine, quetiapine,
      sertraline, topiramate, trazodone, triazolam, venlafaxine, and zolpidem. A
      detailed pharmacological history and a sample of hair were collected for each
      patient. Hair samples were analyzed by liquid chromatography-electrospray tandem
      mass spectrometry, using a previously developed method. RESULTS: All 23 drugs
      were detected in the examined hair samples. The agreement between the self
      reported drug and the drug found in hair was excellent for most analytes (P <
      0.001, Cohen's kappa); a statistically significant relationship (P < 0.05, linear
      regression analysis) between dose and hair level was found for amitriptyline,
      citalopram, delorazepam, duloxetine, lorazepam, and venlafaxine. CONCLUSIONS:
      Hair analysis proved to be a unique matrix to document chronic drug use in
      headache patients, and the level found for each individual drug can represent a
      reliable marker of adherence to pharmacological treatments.

PMID- 27866244
TI  - Efficacy and safety of nab-paclitaxel in patients with previously treated
      metastatic colorectal cancer: a phase II COLO-001 trial.
AB  - PURPOSE: This single-arm, phase II trial evaluated nab-paclitaxel monotherapy in
      pretreated patients with metastatic colorectal cancer (mCRC). METHODS: Patients
      with mCRC (RAS wild-type and RAS mutant cohorts) received nab-paclitaxel 125
      mg/m2 days 1, 8, and 15 (28-day cycle). The primary endpoint was investigator
      assessed progression-free survival (PFS) rate at week 8; secondary endpoints
      included overall survival, overall response rate, and safety. Stage 1 planned
      enrollment was 15 patients per cohort per Simon 2-stage design. Stage 2
      enrollment was to continue unless <=8 of the first 15 patients per cohort
      achieved PFS at 8 weeks. RESULTS: Stage 1 enrolled 41 patients (RAS wild type: n
      = 18; RAS mutant: n = 23). In both RAS cohorts, 3 of 15 patients initially
      enrolled were progression-free at week 8 (20%; 95% CI 4.0-48.0). Median PFS was
      8.1 weeks (95% CI 7.7-8.6) and 7.9 weeks (95% CI 7.6-8.0) for RAS wild-type and
      RAS mutant cohorts, respectively. There were no complete or partial responses.
      The overall disease control rate was 16% (95% CI 6.0-32.0), and rates were
      similar in the RAS wild-type and RAS mutant cohorts (18 and 15%, respectively).
      No new safety signals were reported; the most common grade >=3 adverse events
      included neutropenia, asthenia, and peripheral neuropathy. This study did not
      progress to stage 2 per the preplanned statistical stopping rule. CONCLUSIONS: In
      patients with heavily pretreated mCRC, nab-paclitaxel did not demonstrate
      promising antitumor activity; further assessment of nab-paclitaxel monotherapy in
      this population of patients is not supported. TRIAL REGISTRATION: NCT02103062.

PMID- 27866245
TI  - The impact of socioeconomic status on perioperative complications and oncologic
      outcomes in patients undergoing radical cystectomy.
AB  - PURPOSE: To examine if patients of lower socioeconomic status (SES) are at higher
      risk of perioperative complications and experience different oncologic outcomes
      after radical cystectomy (RC). METHODS: Retrospective review was performed on 383
      consecutive non-metastatic patients who underwent definitive RC at a tertiary
      referral center. Along with clinical and pathologic parameters traditionally
      utilized for risk stratification, potential social determinants of health were
      estimated using US Census data. Zip code-derived proxies of SES included median
      annual household income and percentage of residents completing high school
      education. Patients were grouped based on SES parameters, and potential
      differences were assessed. Multivariable logistic regression was then performed
      to identify predictors of complication within 90 days of RC. Survival outcomes
      were plotted using Kaplan-Meier survival curves. RESULTS: Overall, 167 (46.2%)
      patients suffered any complication within 90 days of RC. On multivariable
      analysis, length of stay (p <= 0.001), lower income grouping (p = 0.03), and
      lowest education tertile (p = 0.007) were significant predictors of any
      complication. Income (p = 0.04) and education (p = 0.008) groupings remained
      significant predictors in a subset analysis looking specifically at post
      discharge complications. No significant differences in recurrence-free or overall
      survival estimates were observed among education (log-rank test: p > 0.9 and p =
      0.6, respectively) or income (log-rank test: p = 0.2 and p = 0.09, respectively)
      groupings. CONCLUSION: Patients of lower socioeconomic status who undergo RC for
      bladder cancer are at increased risk of perioperative complications. Further
      studies are needed to clarify this relationship, and to explore interventions
      aimed to improve outcomes.

PMID- 27866246
TI  - Comparison of Self-Efficacy for Managing Chronic Disease between patients with
      systemic sclerosis and other chronic conditions: a systematic review.
AB  - The complexity and burden of systemic sclerosis (SSc) pose challenges to
      developing and sustaining disease management self-efficacy. The objective of this
      systematic review was to compare scores on a commonly used self-efficacy measure,
      the Self-Efficacy for Managing Chronic Disease (SEMCD) Scale, between SSc and
      other diseases. Data sources included the CINAHL, EMBASE, MEDLINE, and Scopus
      databases, searched through January 25, 2016, and reference lists of included
      articles and relevant reviews. Studies in any language that reported total SEMCD
      scores or individual item scores in adult non-psychiatric medical patients were
      eligible. We identified one eligible non-intervention study of SSc patients (n =
      553), 13 other non-intervention studies, and 21 studies with pre-intervention
      data for patients enrolled in a self-management program or a trial of a program.
      Of 13 non-intervention studies with published total score means in cancer,
      cardiovascular disease, Parkinson's disease, spinal cord injuries, organ
      transplant candidates and recipients, dialysis, and lupus, SEMCD scores were
      statistically significantly lower (poorer self-efficacy) in SSc than 6 other
      disease samples, not significantly different from 6, and significantly higher
      than lupus patients. Compared to 18 studies of patients in self-management
      programs or trials with published total score means, SSc patients were similar or
      lower than 9 samples and significantly higher than 9 samples. Compared to
      patients with other diseases not enrolled in programs to improve self-efficacy,
      SSc patients report lower self-efficacy scores than most patient groups.
      Rigorously tested self-care interventions designed to meet the unique needs of
      patients with SSc are needed.

PMID- 27866247
TI  - Identification of potential peripheral blood diagnostic biomarkers for patients
      with juvenile idiopathic arthritis by bioinformatics analysis.
AB  - Juvenile idiopathic arthritis (JIA) is common childhood rheumatic disease harming
      children health. However, there is still lack of effective biomarkers for
      diagnosis JIA at early onset. We aim to construct a classification model to
      predict JIA disease. The peripheral blood gene expression profile data of JIA
      were downloaded from GEO database. We compared and analyzed differentially
      expressed genes (DEGs) between different JIA samples through Pearson's
      correlation coefficient method and unsupervised clustering analysis. Diagnostic
      model were constructed based on the deviation pathway through bioinformatics
      method. Eighteen specific correlated DEGs were obtained, but the correlations
      altered in different disease states. Although most JIA and control samples were
      clustered by unsupervised clustering analysis, respectively, a few JIA samples
      could not be clustered well. Four co-expression networks were next constructed
      with gene connections dynamically altered under variable conditions. Eight
      signaling pathways were significantly enriched including B/T cell receptor, ErbB
      and MAPK signaling pathways. The deviation scores of pathways were calculated.
      Applying these eight signaling pathways as feature to construct a classification
      model could predict JIA disease with high accuracies. Our data provide some light
      into pathogenic mechanism of JIA, the specific gene sets and the related
      signaling pathways may be potential biomarkers for diagnosis or therapeutic
      targets of JIA.

PMID- 27866248
TI  - Microanatomy of the brachial plexus roots and its clinical significance.
AB  - PURPOSE: To provide the anatomical basis of brachial plexus roots for the
      diagnosis and treatment of brachial plexus root avulsion injury. METHODS: The
      morphological features of brachial plexus roots were observed and measured on 15
      cervicothoracic spine of adult cadavers. The relationship of brachial plexus
      nerve roots and the surrounding tissues also were observed, as well as the blood
      supply of anterior and posterior roots of the brachial plexus. RESULTS:
      Origination of the nerve roots in the dorsal-ventral direction from the midline
      was fine-tuned at each level along the spinal cord. The minimum distance of the
      origin of the nerve root to midline was 2.2 mm at C 5, while the maximum was 3.1
      mm at T 1. Inversely, the distance between the origin of the posterior root and
      the midline of the spinal cord gradually decreased, the maximum being 4.2 mm at C
      5 and minimum 2.7 mm at T 1. Meanwhile, there was complicated fibrous connection
      among posterior roots of the brachial plexus. The C 5-6 nerve roots interlaced
      with tendons of the scalenus anterior and scalenus medius and fused with the
      transverse-radicular ligaments in the intervertebral foramina. However, these
      ligaments were not seen in C 7-8, and T 1. The blood supply of the anterior and
      posterior roots of the brachial plexus was from the segmental branches of the
      vertebral artery, deep cervical artery and ascending cervical artery, with a mean
      outer diameter of 0.61 mm. CONCLUSIONS: The systematic and comprehensive anatomic
      data of the brachial plexus roots provides the anatomical basis to diagnose and
      treat the brachial plexus root avulsion injury.

PMID- 27866249
TI  - Investigation of Endophytic Bacterial Community in Supposedly Axenic Cultures of
      Pineapple and Orchids with Evidence on Abundant Intracellular Bacteria.
AB  - Asepsis, defined as the absence of microbial contamination, is one of the most
      important requirements of plant micropropagation. In long-term micropropagated
      cultures, there may occasionally occur scattered microorganism growth in the
      culture medium. These microorganisms are common plant components and are known as
      latent endophytes. Thus, the aim of this research was to investigate the presence
      of endophytic bacteria in asymptomatic pineapple and orchid microplants, which
      were cultivated in three laboratories for 1 year. Isolation and characterization
      of bacterial isolates, PCR-DGGE from total genomic DNA of microplants and
      ultrastructural analysis of leaves were performed. In the culture-dependent
      technique, it was only possible to obtain bacterial isolates from pineapple
      microplants. In this case, the bacteria genera identified in the isolation
      technique were Bacillus, Acinetobacter, and Methylobacterium. The scanning
      electron microscopy and transmission electron microscopy (SEM and TEM) analyses
      revealed the presence of endophytic bacteria in intracellular spaces in the
      leaves of pineapple and orchid microplants, independent of the laboratory or
      cultivation protocol. Our results strongly indicate that there are endophytic
      bacterial communities inhabiting the microplants before initiation of the in
      vitro culture and that some of these endophytes persist in their latent form and
      can also grow in the culture medium even after long-term micropropagation, thus
      discarding the concept of "truly axenic plants."

PMID- 27866252
TI  - Identification of alkaline phosphatase genes for utilizing a flame retardant,
      tris(2-chloroethyl) phosphate, in Sphingobium sp. strain TCM1.
AB  - Tris(2-chloroethyl) phosphate (TCEP) is a haloalkyl phosphate flame retardant and
      plasticizer that has been recognized as a global environmental contaminant.
      Sphingobium sp. strain TCM1 can utilize TCEP as a phosphorus source. To identify
      the phosphomonoesterase involved in TCEP utilization, we identified four putative
      alkaline phosphatase (APase) genes, named SbphoA, SbphoD1, SbphoD2, and SbphoX
      II, in the genome sequence. Following expression of these genes in Escherichia
      coli, APase activity was confirmed for the SbphoA and SbphoX-II gene products but
      was not clearly observed for the SbphoD1 and SbphoD2 gene products, owing to
      their accumulation in inclusion bodies. The single deletion of either SbphoA or
      SbphoX-II retarded the growth and reduced the APase activity of strain TCM1 cells
      on medium containing TCEP as the sole phosphorus source; these changes were more
      marked in cells with the SbphoX-II gene deletion. In contrast, the deletion of
      either SbphoD1 or SbphoD2 had no effect on cell growth or APase activity. The
      double deletion of SbphoA and SbphoX-II resulted in the complete loss of cell
      growth on TCEP. These results show that SbPhoA and SbPhoX-II are involved in the
      utilization of TCEP as a phosphorus source and that SbPhoX-II is the major
      phosphomonoesterase involved in TCEP utilization.

PMID- 27866251
TI  - Diversity, abundance, and possible sources of fecal bacteria in the Yangtze
      River.
AB  - The fecal bacteria in natural waters may pose serious risks on human health.
      Although many source tracking methods have been developed and used to determine
      the possible sources of the fecal pollution, little is known about the overall
      diversity and abundance of fecal bacterial community in natural waters. In this
      study, a method based on fecal bacterial sequence library was introduced to
      evaluate the fecal bacterial profile in the Yangtze River (Nanjing section). Our
      results suggested that the Yangtze River water harbors diverse fecal bacteria.
      Fifty-eight fecal operational taxonomic units (97% identity level) were detected
      in the Yangtze River water samples and the relative abundance of fecal bacteria
      in these samples ranged from 0.1 to 8%. It was also found that the relative
      abundances of the fecal bacteria in locations near to the downstream of
      wastewater treatment plants were obviously higher than those in other locations.
      However, the high abundance of fecal bacteria could decrease to the normal level
      in 2~4 km in the river due to degradation or dilution, and the overall fecal
      bacteria level changed little when the Yangtze River flew through the Nanjing
      City. Moreover, the fecal bacteria in the Yangtze River water were found to be
      highly associated (Spearman rho = 0.804, P < 0.001) with the potential pathogenic
      bacteria. Collectively, the findings in this study reveal the diversity,
      abundance, and possible sources of fecal bacteria in the Yangtze River and
      advance our understandings of the fecal bacteria community in the natural waters.

PMID- 27866250
TI  - iTRAQ-Based Comparative Proteomics Analysis of the Fruiting Dikaryon and the Non
      fruiting Monokaryon of Flammulina velutipes.
AB  - Flammulina velutipes is a potentially excellent fungus to study basic mechanisms
      of basidiomycete mycelium biology. To provide a better understanding of the
      mechanism of hyphae growth and fruit-body formation, the biological functions of
      the differentially abundant proteins between the fruiting dikaryon and the non
      fruiting monokaryon of F. velutipes were investigated at the proteomic level
      using iTRAQ-coupled two-dimensional liquid chromatography tandem mass
      spectrometry technique. Among the 1198 proteins identified with high confidence,
      a total of 472 proteins were detected differentially abundant at least one of the
      mycelium development stages. In-depth data analysis revealed that differentially
      expressed proteins were influenced a variety of cellular processes, particularly
      metabolic processes. Functional pathway analysis indicated that 63 up-regulated
      proteins at only the fruiting dikaryon (Fv13) stage were mainly distributed in 51
      specific Kyoto Encyclopedia of Genes and Genome pathways, such as amino acids
      biosynthesis and metabolism, signaling pathway, and central carbon metabolism.
      These up-regulated proteins could possibly serve as potential biomarkers to study
      the mycelium development pathways as well as provide new insights on the mycelium
      heterogenic compatibility and fruit-body formation mechanisms of basidiomycetes.

PMID- 27866253
TI  - Characterization of Clostridium ljungdahlii OTA1: a non-autotrophic hyper ethanol
      producing strain.
AB  - A Clostridium ljungdahlii lab-isolated spontaneous-mutant strain, OTA1, has been
      shown to produce twice as much ethanol as the C. ljungdahlii ATCC 55383 strain
      when cultured in a mixotrophic medium containing fructose and syngas. Whole
      genome sequencing identified four unique single nucleotide polymorphisms (SNPs)
      in the C. ljungdahlii OTA1 genome. Among these, two SNPs were found in the gene
      coding for AcsA and HemL, enzymes involved in acetyl-CoA formation from CO/CO2.
      Homology models of the respective mutated enzymes revealed alterations in the
      size and hydrogen bonding of the amino acids in their active sites. Failed
      attempts to grow OTA1 autotrophically suggested that one or both of these mutated
      genes prevented acetyl-CoA synthesis from CO/CO2, demonstrating that its activity
      was required for autotrophic growth by C. ljungdahlii. An inoperable Wood
      Ljungdahl pathway resulted in higher CO2 and ethanol yields and lower biomass and
      acetate yields compared to WT for multiple growth conditions including
      heterotrophic and mixotrophic conditions. The two other SNPs identified in the C.
      ljungdahlii OTA1 genome were in genes coding for transcriptional regulators
      (CLJU_c09320 and CLJU_c18110) and were found to be responsible for deregulated
      expression of co-localized arginine catabolism and 2-deoxy-D-ribose catabolism
      genes. Growth medium supplementation experiments suggested that increased
      arginine metabolism and 2-deoxy-D-ribose were likely to have minor effects on
      biomass and fermentation product yields. In addition, in silico flux balance
      analysis simulating mixotrophic and heterotrophic conditions showed no change in
      flux to ethanol when flux through HemL was changed whereas limited flux through
      AcsA increased the ethanol flux for both simulations. In characterizing the
      effects of the SNPs identified in the C. ljungdahlii OTA1 genome, a non
      autotrophic hyper ethanol-producing strain of C. ljungdahlii was identified that
      has utility for further physiology and strain performance studies and as a
      biocatalyst for industrial applications.

PMID- 27866254
TI  - Heart-cut achiral-chiral LC-LC method development using factorial design:
      application to the chiral separation of ketoprofen.
AB  - A two-dimensional achiral-chiral LC-LC method in heart-cut mode for ketoprofen
      and its enantiomeric fraction determination was proposed. A C8 column was used in
      the first dimension, and the chiral column was an alpha1-acid glycoprotein. The
      mobile phase of the chiral system was optimized by a factorial design. The effect
      of temperature on retention and on enantiomeric resolution was studied.
      Particular attention was paid to mobile phase compatibility for the two columns
      and to transferring time, using ketoprofen standards. The R-(-) and S-(+)
      ketoprofen retention times were 9 and 11 min, respectively; the resolution was
      higher than 1.1 and enantiomeric fraction close to 0.5. The method was applied to
      capsules and gels containing ketoprofen. Factorial design was also used to
      establish the best conditions for gel sample preparation. Recoveries were 84 and
      105 % for capsules and gels, respectively. Graphical abstract Two-dimensional
      chromatogram for KPF and its enantiomers.

PMID- 27866255
TI  - Erratum to: Diffusive gradients in thin films measurement of sulfur stable
      isotope variations in labile soil sulfate.

PMID- 27866256
TI  - Surfactant-free microemulsion electrokinetic chromatography (SF-MEEKC) with UV
      and MS detection - a novel approach for the separation and ESI-MS detection of
      neutral compounds.
AB  - Microemulsion electrokinetic chromatography (MEEKC) is a powerful tool to
      separate neutral species based on differences in their hydrophobic and
      hydrophilic properties. However, as a major drawback the conventionally used SDS
      based microemulsions are not compatible with electrospray ionization mass
      spectrometry (ESI-MS). In this work, a surfactant-free microemulsion (SFME)
      consisting of water, ethanol, and 1-octanol is used for surfactant-free
      microemulsion electrokinetic chromatography (SF-MEEKC). Ammonium acetate was
      added to the SFME enabling electrophoretic separations. The stability of SFMEs
      containing ammonium acetate was investigated using small-angle X-ray scattering
      and dynamic light scattering. A method for the separation of a model system of
      hydrophobic and hydrophilic neutral vitamins, namely the vitamins B2 and D3, and
      the cationic vitamin B1 was developed using UV/VIS detection. The influence of
      the ammonium acetate concentration on the separation performance was studied in
      detail. The method was characterized concerning reproducibility of migration
      times and peak areas and concerning the linearity of the calibration data.
      Furthermore, SF-MEEKC was coupled to ESI-MS investigating the compatibility
      between SFMEs and the ESI process. The signal intensities of ESI-MS measurements
      of the model analytes were comparable for SFMEs and aqueous systems. Finally, the
      vitamin D3 content of a drug treating vitamin D3 deficiency was determined by SF
      MEEKC coupled to ESI-MS using 25-hydroxycholecalciferol as an internal standard.
      Graphical abstract The concept of surfactant-free microemulsion electrokinetic
      chromatography coupled to electrospray ionization mass spectrometry.

PMID- 27866257
TI  - Detection of methicillin-resistant Staphylococcus aureus using phage
      amplification combined with matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - Antibiotic resistance continues to contribute significantly to morbidity and
      mortality across the world. Developing new tests for antibiotic-resistant
      bacteria is a core action to combat resistant infections. We describe a method
      that uses phage amplification detection (PAD) combined with matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) to rapidly identify
      Staphylococcus aureus and determine phenotypic susceptibility to cefoxitin.
      Samples tested for S. aureus are incubated together with bacteriophage in the
      presence and absence of cefoxitin and subjected to rapid trypsin digestion
      followed by MALDI-MS analysis. Tryptic peptides derived from amplified phage
      proteins can be detected by MALDI-MS, as validated by time-of-flight (TOF)/TOF
      analysis of each peptide combined with database searching. Methicillin-resistant
      S. aureus show significant phage amplification in the presence of cefoxitin,
      while methicillin-sensitive S. aureus show no phage amplification relative to a
      no-antibiotic control. We also show that PAD methodology can be implemented on an
      FDA-approved commercial MALDI-MS bacterial identification system to identify S.
      aureus and determine antibiotic susceptibility. The novelty of this assay
      includes the use of phage-derived tryptic peptides as detected by MALDI-MS to
      monitor the results of PAD on an instrument common to many modern microbiology
      laboratories.

PMID- 27866258
TI  - Fat-containing soft-tissue masses in children.
AB  - The diagnosis of soft-tissue masses in children can be difficult because of the
      frequently nonspecific clinical and imaging characteristics of these lesions.
      However key findings on imaging can aid in diagnosis. The identification of
      macroscopic fat within a soft-tissue mass narrows the differential diagnosis
      considerably and suggests a high likelihood of a benign etiology in children. Fat
      can be difficult to detect with sonography because of the variable appearance of
      fat using this modality. Fat is easier to recognize using MRI, particularly with
      the aid of fat-suppression techniques. Although a large portion of fat-containing
      masses in children are adipocytic tumors, a variety of other tumors and mass-like
      conditions that contain fat should be considered by the radiologist confronted
      with a fat-containing mass in a child. In this article we review the sonographic
      and MRI findings in the most relevant fat-containing soft-tissue masses in the
      pediatric age group, including adipocytic tumors (lipoma, angiolipoma,
      lipomatosis, lipoblastoma, lipomatosis of nerve, and liposarcoma);
      fibroblastic/myofibroblastic tumors (fibrous hamartoma of infancy and
      lipofibromatosis); vascular anomalies (involuting hemangioma, intramuscular
      capillary hemangioma, phosphate and tensin homologue (PTEN) hamartoma of soft
      tissue, fibro-adipose vascular anomaly), and other miscellaneous entities, such
      as fat necrosis and epigastric hernia.

PMID- 27866261
TI  - Anticipatory postural adjustments and anticipatory synergy adjustments: preparing
      to a postural perturbation with predictable and unpredictable direction.
AB  - We explored two aspects of feed-forward postural control, anticipatory postural
      adjustments (APAs) and anticipatory synergy adjustments (ASAs) seen prior to self
      triggered unloading with known and unknown direction of the perturbation. In
      particular, we tested two main hypotheses predicting contrasting changes in APAs
      and ASAs. The first hypothesis predicted no major changes in ASAs. The second
      hypothesis predicted delayed APAs with predominance of co-contraction patterns
      when perturbation direction was unknown. Healthy subjects stood on the force
      plate and held a bar with two loads acting in the forward and backward
      directions. They pressed a trigger that released one of the loads causing a
      postural perturbation. In different series, the direction of the perturbation was
      either known (the same load released in all trials) or unknown (the subjects did
      not know which of the two loads would be released). Surface electromyograms were
      recorded and used to quantify APAs, synergies stabilizing center of pressure
      coordinate (within the uncontrolled manifold hypothesis), and ASA. APAs and ASAs
      were seen in all conditions. APAs were delayed, and predominance of co
      contraction patterns was seen under the conditions with unpredictable direction
      of perturbation. In contrast, no significant changes in synergies and ASAs were
      seen. Overall, these results show that feed-forward control of vertical posture
      has two distinct components, reflected in APAs and ASAs, which show qualitatively
      different adjustments with changes in predictability of the direction of
      perturbation. These results are interpreted within the recently proposed
      hierarchical scheme of the synergic control of motor tasks. The observations
      underscore the complexity of the feed-forward postural control, which involves
      separate changes in salient performance variables (such as coordinate of the
      center of pressure) and in their stability properties.

PMID- 27866260
TI  - Isolation and characterization of a novel cadmium-regulated Yellow Stripe-Like
      transporter (SnYSL3) in Solanum nigrum.
AB  - KEY MESSAGE: SnYSL3 encodes a plasma-localized transporter delivering various
      metal-nicotianamine complexes. The expression of SnYSL3 is up-regulated by excess
      Cd, suggesting an important role for SnYSL3 in response to Cd stress. The Yellow
      Stripe-Like (YSL) transporters have been proposed to participate in metal uptake
      and long-range transport in model plants. In this study, we isolated and
      characterized a novel member of the YSL gene family, SnYSL3, from the cadmium
      hyperaccumulator Solanum nigrum. SnYSL3 was constitutively expressed and encodes
      a plasma membrane-localized protein. In situ RNA hybridization localized the
      SnYSL3 transcripts predominantly in vascular tissues and epidermal cells of the
      roots and stems, while in leaves, the mRNA levels were high in the vasculature.
      The SnYSL3 expression level was up-regulated by excess Cd, excess Fe and Cu
      deficiency. Heterologous expression of SnYSL3 in yeast revealed that SnYSL3
      transports nicotianamine complexes containing Fe(II), Cu, Zn and Cd. SnYSL3
      overexpression in Arabidopsis thaliana decreased Fe and Mn concentrations in the
      roots and increased the root-to-shoot translocation ratios of Fe and Mn. Under Cd
      exposure, the transgenic plants showed increased translocation ratios of Fe and
      Cd, but no difference was observed in Mn translocation from roots to shoots
      between the transgenic and wild-type lines. Although the accurate function of
      SnYSL3 remains to be confirmed, these results suggest that SnYSL3 is a
      transporter delivering a broad range of metal-nicotianamine complexes and is
      potentially important for the response to heavy metal stress, especially due to
      Cd and Fe.

PMID- 27866262
TI  - Impairment of mitochondria dynamics by human A53T alpha-synuclein and rescue by
      NAP (davunetide) in a cell model for Parkinson's disease.
AB  - The formation of oligomers and aggregates of overexpressed or mutant alpha
      synuclein play a role in the degeneration of dopaminergic neurons in Parkinson's
      disease by causing dysfunction of mitochondria, reflected in their disturbed
      mobility and production of ROS. The mode of action and mechanisms underlying this
      mitochondrial impairment is still unclear. We have induced stable expression of
      wild-type, A30P or A53T alpha-synuclein in neuronally differentiated SH-SY5Y
      neuroblastoma cells and studied anterograde and retrograde mitochondrial
      trafficking in this cell model for Parkinson's disease. In contrast to wild-type
      and A30P, A53T alpha-synuclein significantly inhibited mitochondrial trafficking,
      at first retrogradely and in a later stage anterogradely. Accordingly, A53T alpha
      synuclein also caused the highest increase in ROS production in the dysmobilized
      mitochondria in comparison to wild-type or A30P alpha-synuclein. Treatment with
      NAP, the eight amino acid peptide identified as the active component of activity
      dependent neuroprotective protein (ADNP), completely annihilated the adverse
      effects of A53T on mitochondrial dynamics. Our results reveal that A53T alpha
      synuclein (oligomers or aggregates) leads to the inhibition of mitochondrial
      trafficking, which can be rescued by NAP, suggesting the involvement of
      microtubule disruption in the pathophysiology of Parkinson's disease.

PMID- 27866263
TI  - Aperture extent and stimulus speed affect the perception of visual acceleration.
AB  - Humans are generally poor at detecting the presence of visual acceleration, but
      it is unclear whether the extent of a field of moving objects through an aperture
      affects this ability. Hypothetically, the farther a stimulus can accelerate
      uninterrupted by an aperture's physical constraints, the easier it should be to
      discern its motion profile. We varied the horizontal extent of the aperture
      through which continuously accelerating or decelerating random dot arrays were
      presented at different average speeds, and measured acceleration and deceleration
      detection thresholds. We also hypothesized that manipulating aperture extent at
      different speeds would change how observers visually pursue acceleration, which
      we tested in a control experiment. Results showed that, while there was no
      difference between the acceleration and deceleration conditions, detection was
      better in the larger than small aperture conditions. Regardless of aperture size,
      smaller acceleration and deceleration rates (relative to average speed) were
      needed to detect changing speed in faster than slower speed ranges. Similarly,
      observers tracked the stimuli to a greater extent in the larger than small
      apertures, and smooth pursuit was overall poorer at faster than slower speeds.
      Notably, the effect of speed on pursuit was greater for the larger than small
      aperture conditions, suggesting that the small aperture restricted pursuit.
      Furthermore, there was little difference in psychophysical and eye movement data
      between the medium and large aperture conditions within each speed range,
      indicating that it is easier to detect an accelerating profile when the aperture
      is large enough to encourage a minimum level of pursuit.

PMID- 27866264
TI  - Effects of intentional movement preparation on response times to symbolic and
      imitative cues.
AB  - Speeded responses to an external cue are slower when the cue interrupts
      preparation to perform the same or a similar action in a self-paced manner. To
      explore the mechanism underlying this 'cost of intention', we examined whether
      the size of the cost is influenced by the nature of the external cue.
      Specifically, we assessed whether the cost of intention is different for
      movements made in response to an imitative cue (an on-screen hand movement)
      compared to those made in response to a symbolic cue. Consistent with previous
      reports, externally cued responses were significantly slower on trials where
      participants were preparing to perform an internally driven movement later in the
      trial. Also as predicted, simple response times to the imitative cue were faster
      than those made to the symbolic cue. Critically, the cost of intention was
      similar for each cue type, suggesting that preparing an intentional action
      influenced responses cued by the symbolic and imitative cues to a similar degree.
      These findings suggest that the nature of the external cue does not influence the
      response time delay associated with concurrent intentional preparation. Together
      with previous findings, the results of the current study shed further light on
      the potential mechanisms underlying the cost of intention.

PMID- 27866266
TI  - Survey of Baylisascaris spp. in captive striped skunks (Mephitis mephitis) in
      some European areas.
AB  - Skunks are popular carnivore species kept both in zoological institutions and in
      households where they are hand raised as exotic pets. These small carnivores are
      considered the main definitive hosts of the roundworm Baylisascaris columnaris.
      The purpose of this survey was to investigate the occurrence of Baylisascaris
      spp. in striped skunks kept as pets or in private zoo collections in some
      European areas. Copromicroscopic data from two laboratories, one in Italy and one
      in Germany, were used. A total of 60 animals were selected. Samples came from
      Germany (n = 30), Italy (n = 23), United Kingdom (n = 5), Austria (n = 1), and
      the Netherlands (n = 1). Twenty-eight animals were certainly kept as pets in
      private households in Italy and the UK. Fifteen out of 60 animals (25%) were
      positive for Baylisascaris spp. Molecular identification of adult parasites was
      performed in ten of those animals, revealing B. columnaris in all cases. To the
      authors' knowledge, this is the first survey of Baylisascaris spp. in captive
      skunks in Europe.

PMID- 27866265
TI  - Proteomic analysis of Fasciola hepatica excretory and secretory products (FhESPs)
      involved in interacting with host PBMCs and cytokines by shotgun LC-MS/MS.
AB  - Fasciola hepatica is a helminth parasite with a worldwide distribution, which can
      cause chronic liver disease, fasciolosis, leading to economic losses in the
      livestock and public health in many countries. Control is mostly reliant on the
      use of drugs, and as a result, drug resistance has now emerged. The
      identification of F. hepatica genes involved in interaction between the parasite
      and host immune system is utmost important to elucidate the evasion mechanisms of
      the parasite and develop more effective strategies against fasciolosis. In this
      study, we aimed to identify molecules in F. hepatica excretory and secretory
      products (FhESPs) interacting with the host peripheral blood mononuclear cells
      (PBMCs), Th1-like cytokines (IL2 and IFN-gamma), and Th17-like cytokines (IL17)
      by Co-IP combined with tandem mass spectrometry. The results showed that 14, 16,
      and 9 proteins in FhESPs could bind with IL2, IL17, and IFN-gamma, respectively,
      which indicated that adult F. hepatica may evade the host immune responses
      through directly interplaying with cytokines. In addition, nine proteins in
      FhESPs could adhere to PBMCs. Our findings provided potential targets as immuno
      regulators, and will be helpful to elucidate the molecular basis of host-parasite
      interactions and search for new potential proteins as vaccine and drug target
      candidates.

PMID- 27866267
TI  - Luminol testing in detecting modern human skeletal remains: a test on different
      types of bone tissue and a caveat for PMI interpretation.
AB  - When forensic pathologists and anthropologists have to deal with the evaluation
      of the post-mortem interval (PMI) in skeletal remains, luminol testing is
      frequently performed as a preliminary screening method. However, the
      repeatability of this test on the same bone, as well as comparative studies on
      different bones of the same individual, has never been performed. Therefore, with
      the aim of investigating the influence that different types of bones may exert on
      the response to the luminol test, the present study analysed three different
      skeletal elements (femoral diaphysis, vertebra and cranial vault), gathered from
      ten recent exhumed skeletons (all with a 20-year PMI). The analysis was performed
      twice on the same bone after 2 months: the analysis at time 0 concerned the whole
      bone, whereas the second concerned only a part of the same bone taken during the
      first test (which already had been broken). The overall results showed different
      responses, depending on the type of bone and on the integrity of the samples.
      Negative results at the first analysis (6.6% out of the total of samples) are
      consistent with what is reported in the literature, whilst at the second
      analysis, the increase of about 20% of false-negative results highlights that the
      luminol test ought to be performed with caution in case of broken bones or
      elements which are taphonomically altered. Results have thus proven that the
      exposition to environmental agents might result in haemoglobin (Hb) loss, as
      detected even after only 2 months. The study also focused on the crucial issue of
      the type of bone subjected to testing, remarking the suitability of the femoral
      diaphysis (100% of positive responses at the first analysis vs only 18% of false
      negative results at the second test, corresponding to 5% of total false-negative
      results) as opposed to other bone elements that showed a low yield. In
      particular, the cranial vault gave poor results, with 40% of discrepancy between
      results from the two analyses, which suggests caution in choosing the type of
      bone sample to test. In conclusion, luminol testing should be used with caution
      on bones different from long bones or on non-intact bones.

PMID- 27866269
TI  - Effects of alexithymia and empathy on the neural processing of social and
      monetary rewards.
AB  - Empathy has been found to affect the neural processing of social and monetary
      rewards. Alexithymia, a subclinical condition showing a close inverse
      relationship with empathy is linked to dysfunctions of socio-emotional processing
      in the brain. Whether alexithymia alters the neural processing of rewards, which
      is currently unknown. Here, we investigated the influence of both alexithymia and
      empathy on reward processing using a social incentive delay (SID) task and a
      monetary incentive delay (MID) task in 45 healthy men undergoing functional
      magnetic resonance imaging. Controlling for temperament-character dimensions and
      rejection sensitivity, the relationship of alexithymia and empathy with neural
      activity in several a priori regions of interest (ROIs) was examined by means of
      partial correlations, while participants anticipated and received social and
      monetary rewards. Results were considered significant if they survived Holm
      Bonferroni correction for multiple comparisons. Alexithymia modulated neural
      activity in several ROIs of the emotion and reward network, both during the
      anticipation of social and monetary rewards and in response to the receipt of
      monetary rewards. In contrast, empathy did not affect reward anticipation and
      modulated ROI activity only in response to the receipt of social rewards. These
      results indicate a significant influence of alexithymia on the processing of
      social and monetary rewards in the healthy brain.

PMID- 27866268
TI  - A genome-wide association study of essential hypertension in an Australian
      population using a DNA pooling approach.
AB  - Despite the success of genome-wide association studies (GWAS) in detecting
      genetic loci involved in complex traits, few susceptibility genes have been
      detected for essential hypertension (EH). We aimed to use pooled DNA GWAS
      approach to identify and validate novel genomic loci underlying EH susceptibility
      in an Australian case-control population. Blood samples and questionnaires
      detailing medical history, blood pressure, and prescribed medications were
      collected for 409 hypertensives and 409 age-, sex- and ethnicity-matched
      normotensive controls. Case and control DNA were pooled in quadruplicate and
      hybridized to Illumina 1 M-Duo arrays. Allele frequencies agreed with those
      reported in reference data and known EH association signals were represented in
      the top-ranked SNPs more frequently than expected by chance. Validation showed
      that pooled DNA GWAS gave reliable estimates of case and control allele
      frequencies. Although no markers reached Bonferroni-corrected genome-wide
      significance levels (5.0 * 10-8), the top marker rs34870220 near ASGR1 approached
      significance (p = 4.32 * 10-7), as did several candidate loci (p < 1 * 10-6) on
      chromosomes 2, 4, 6, 9, 12, and 17. Four markers (located in or near genes NHSL1,
      NKFB1, GLI2, and LRRC10) from the top ten ranked SNPs were individually genotyped
      in pool samples and were tested for association between cases and controls using
      the chi 2 test. Of these, rs1599961 (NFKB1) and rs12711538 (GLI2) showed
      significant difference between cases and controls (p < 0.01). Additionally, four
      top-ranking markers within NFKB1 were found to be in LD, suggesting a single
      strong association signal for this gene.

PMID- 27866270
TI  - Relationship among interthalamic adhesion size, thalamic anatomy and
      neuropsychological functions in healthy volunteers.
AB  - The interthalamic adhesion (ITA) is an understudied neuroanatomical structure
      that forms a bridge of tissue connecting the thalamus of each hemisphere across
      the midline whose functional significance remains largely unknown. The likelihood
      of ITA absence has been reported in some studies to be increased in males, but
      findings have been inconsistent. We used magnetic resonance imaging to
      investigate the size and absence of the ITA and their relationship to thalamic
      volume, putative indices of white matter integrity (fractional anisotropy and
      mean diffusivity) within the anterior thalamic radiation and neuropsychological
      functions in 233 (129 M/104 F) healthy volunteers (age range 8-68). To ensure
      high reliability in this study two operators independently rated the absence of
      the ITA and measured its size for all individuals. The ITA was absent in 4% of
      all individuals with no sex differences in its absence. Females had greater ITA
      size compared to males overall with both groups demonstrating nonlinear age
      associated changes across the age range examined. ITA size among females
      correlated significantly with thalamus volume and lower mean diffusivity in the
      anterior thalamic radiation. Path modeling indicated that ITA size statistically
      mediated the relationship between age and attention among females. Our findings
      provide evidence for sex differences in ITA size across the lifespan, which are
      associated with the surrounding thalamic anatomy and neuropsychological
      functions.

PMID- 27866271
TI  - Paediatric biobanking: Dutch experts reflecting on appropriate legal standards
      for practice.
AB  - : Large sets of data and human specimens, such as blood, tumour tissue and DNA,
      are deposited in biobanks for research purposes, preferably for long periods of
      time and with broadly defined research aims. Our research focuses on the
      retention of data and biological materials obtained from children. However
      important such paediatric biobanks may be, the privacy interests of the children
      involved and the related risks may not be ignored. The privacy issues arising
      from paediatric biobanks are the central focus of this article. We first review
      the international regulations that apply to biobanks and then summarise
      viewpoints expressed by experts in a round-table discussion. We confine ourselves
      here to two normative questions: (1) How much control should children's parents
      or legal representatives, and later the children themselves, have over the stored
      materials and data? (2) What should be done if research findings emerge that have
      serious implications for a child's health? CONCLUSION: On the basis of
      international legal standards and the views of experts, involved in paediatric
      biobanking, we argue that biological material of children may only be stored in a
      biobank for scientific purposes if parents provide their explicit consent, the
      child is re-contacted at 16 or 18 years of age to reconsider storage and use of
      its material, and the biobank maintains a limited policy in disclosure of
      individual research findings to the child's parents. What is Known: *
      Increasingly, biological material of children is stored in biobanks for research
      purposes. * Clear standards on the conditions under which children's cells or
      tissues may be stored and used are lacking. What is New: * According to experts,
      storage and use of children's materials should only be allowed if performed in
      accordance with appropriate consent procedures and feedback policies.

PMID- 27866272
TI  - Angry but not neutral faces facilitate response inhibition in schizophrenia
      patients.
AB  - Schizophrenia is a very heterogeneous disorder with extensive impairments in
      cognitive as well as emotional abilities. One critical domain is response
      inhibition, and previous studies in schizophrenia patients have mostly observed
      impairments, i.e., slower inhibition. Moreover, response inhibition to socially
      salient stimuli has not been investigated in schizophrenia so far. Therefore, to
      elucidate emotion-cognition interactions by examining potential emotional effects
      on inhibition processes and further investigate the association of cognition with
      inhibition we used an emotional stop signal task in 27 schizophrenia patients and
      27 gender- and age-matched controls. Task irrelevant emotional faces (angry and
      neutral) were used as stimuli in a stop signal reaction time task. Regarding
      accuracy, patients showed significantly worse performance in neutral trials,
      while their performance in anger trials (stop and go) was similar to controls.
      Angry faces elicited faster response inhibition in both groups, underlining an
      emotional facilitation effect. Neurocognitive functions significantly correlated
      with accuracy in the stop signal task in schizophrenia patients, thus further
      strengthening the notion of the strong link between cognitive abilities and
      inhibition processes. Inhibitory control impairments are of high clinical
      interest due to their association with substance abuse, impulsive behavior and
      suicide. Based on our data, neutral faces significantly affect response
      inhibition in schizophrenia while an emotional facilitation effect was apparent
      for angry faces even in schizophrenia patients. Thus, our data further support
      the notion that neutral face processing is critically impaired in schizophrenia.

PMID- 27866275
TI  - Clinical relevance for the use of ozone to enhance the remineralizing potential
      of n-HAP on initial enamel lesions.

PMID- 27866273
TI  - Omeprazole suppressed plasma magnesium level and duodenal magnesium absorption in
      male Sprague-Dawley rats.
AB  - Hypomagnesemia is the most concerned side effect of proton pump inhibitors (PPIs)
      in chronic users. However, the mechanism of PPIs-induced systemic Mg2+ deficit is
      currently unclear. The present study aimed to elucidate the direct effect of
      short-term and long-term PPIs administrations on whole body Mg2+ homeostasis and
      duodenal Mg2+ absorption in rats. Mg2+ homeostasis was studied by determining the
      serum Mg2+ level, urine and fecal Mg2+ excretions, and bone and muscle Mg2+
      contents. Duodenal Mg2+ absorption as well as paracellular charge selectivity
      were studied. Our result showed that gastric and duodenal pH markedly increased
      in omeprazole-treated rats. Omeprazole significantly suppressed plasma Mg2+
      level, urinary Mg2+ excretion, and bone and muscle Mg2+ content. Thus, omeprazole
      induced systemic Mg2+ deficiency. By using Ussing chamber techniques, it was
      shown that omeprazole markedly suppressed duodenal Mg2+ channel-driven and Mg2+
      channel-independent Mg2+ absorptions and cation selectivity. Inhibitors of
      mucosal HCO3- secretion significantly increased duodenal Mg2+ absorption in
      omeprazole-treated rats. We therefore hypothesized that secreted HCO3- in
      duodenum decreased luminal proton, this impeded duodenal Mg2+ absorption. Higher
      plasma total 25-OH vitamin D, diuresis, and urine PO43- were also demonstrated in
      hypomagnesemic rats. As a compensatory mechanism for systemic Mg2+ deficiency,
      the expressions of duodenal transient receptor potential melastatin 6 (TRPM6),
      cyclin M4 (CNNM4), claudin (Cldn)-2, Cldn-7, Cldn-12, and Cldn-15 proteins were
      enhanced in omeprazole-treated rats. Our findings support the potential role of
      duodenum on the regulation of Mg2+ homeostasis.

PMID- 27866274
TI  - Ryanodine receptor type 3 does not contribute to contractions in the mouse
      myometrium regardless of pregnancy.
AB  - Ryanodine receptor type 3 (RyR3) is expressed in myometrial smooth muscle cells
      (MSMCs). The short isoform of RyR3 is a dominant negative variant (DN-RyR3) and
      negatively regulates the functions of RyR2 and full-length (FL)-RyR3. DN-RyR3 has
      been suggested to function as a major RyR3 isoform in non-pregnant (NP) mouse
      MSMCs, and FL-RyR3 may also be upregulated during pregnancy (P). This increase in
      the FL-RyR3/DN-RyR3 ratio may contribute to the strong contractions by MSMCs for
      parturition. In the present study, spontaneous contractions by the myometrium in
      NP and P mice were highly susceptible to nifedipine but were not affected by
      ryanodine. Ca2+ image analyses under a voltage clamp revealed that the influx of
      Ca2+ through voltage-dependent Ca2+ channels did not cause the release of Ca2+
      from the sarcoplasmic reticulum (SR). Cytosolic Ca2+ concentrations ([Ca2+]cyt)
      in MSMCs were not affected by caffeine. Despite the abundant expression of large
      conductance Ca2+-activated K+ channels in MSMCs, spontaneous transient outward
      currents were not observed in the resting state because of the substantive lack
      of Ca2+ sparks. Quantitative PCR and Western blot analyses indicated that DN-RyR3
      was strongly expressed in the NP myometrium, while the expression of FL-RyR3 and
      DN-RyR3 was markedly reduced in the P myometrium. The messenger RNA (mRNA)
      expression of RyR2 and RyR1 was negligible in the NP and P myometria. Moreover,
      RyR3 knockout mice may become pregnant and deliver normally. Thus, we concluded
      that none of the RyR subtypes, including RyR3, play a significant role in the
      regulation of [Ca2+]cyt in or contractions by mouse MSMCs regardless of
      pregnancy.

PMID- 27866276
TI  - Manual Intrapleural Saline Flushing Plus Urokinase: A Potentially Useful Therapy
      for Complicated Parapneumonic Effusions and Empyemas.
AB  - PURPOSE: We sought to evaluate the safety profile and effectiveness of manual
      pleural saline flushing, in addition to urokinase, for managing complicated
      parapneumonic effusions and empyemas. METHODS: Retrospective comparative review
      of 23 consecutive patients with complicated parapneumonic effusions or empyemas
      who received saline flushing plus urokinase through small-bore chest catheters,
      and 39 who were only treated with fibrinolytics. Both groups had similar baseline
      characteristics and treatments were mostly protocol-driven. RESULTS: As compared
      with patients only receiving urokinase, those additionally treated with saline
      flushing needed less fibrinolytic doses (a single dose being sufficient in 15 vs
      44%, p = 0.019), chest tube duration (5 vs 2 days, p < 0.01), and length of
      hospital stay (8 vs 6 days, p = 0.011). There were no adverse events attributed
      to saline therapy. CONCLUSIONS: Manual pleural saline flushing via chest tube, in
      addition to urokinase, is a safe and potentially beneficial therapy in patients
      with pleural infection.

PMID- 27866277
TI  - Identification of Key Cost Generating Events for Idiopathic Pulmonary Fibrosis: A
      Systematic Review.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable, debilitating
      disease which impairs lung function and eventually leads to death. Currently,
      there is a lack of effective modifying therapies and treatments for IPF as the
      underlying epidemiological mechanism is not clearly understood. This leads to
      difficulty in diagnosing and managing IPF, which results in a high incurment of
      disease-associated cost. Even though IPF poses a substantial economic burden,
      there is a lack of research available on cost triggers and healthcare
      utilization, which can be a barrier to future economic evaluations of new
      medicines for IPF. OBJECTIVES: We aimed to conduct a systematic literature review
      (SLR) to identify the key cost-generating events of IPF and to gather any related
      costing information. RESULTS: The data showed that the main events triggering
      high resource use in patients were the symptoms of IPF progression along with
      comorbidities and lung transplantations. These events result in a high economic
      impact through the use of medications, health care professionals, and hospital
      stays. CONCLUSION: More research is needed to identify the direct, and indirect,
      relationships between IPF events and the costs they generate. This would help to
      further evaluate the area of need for future health technologies and to
      understand what events should be targeted to reduce the global economic burden of
      IPF.

PMID- 27866279
TI  - High-risk carotid plaques identified by CT-angiogram can predict acute myocardial
      infarction.
AB  - Prior studies identified the incremental value of non-invasive imaging by CT
      angiogram (CTA) to detect high-risk coronary atherosclerotic plaques. Due to
      their superficial locations, larger calibers and motion-free imaging, the carotid
      arteries provide the best anatomic access for the non-invasive characterization
      of atherosclerotic plaques. We aim to assess the ability of predicting
      obstructive coronary artery disease (CAD) or acute myocardial infarction (MI)
      based on high-risk carotid plaque features identified by CTA. We retrospectively
      examined carotid CTAs of 492 patients that presented with acute stroke to
      characterize the atherosclerotic plaques of the carotid arteries and examined
      development of acute MI and obstructive CAD within 12-months. Carotid lesions
      were defined in terms of calcifications (large or speckled), presence of low
      attenuation plaques, positive remodeling, and presence of napkin ring sign.
      Adjusted relative risks were calculated for each plaque features. Patients with
      speckled (<3 mm) calcifications and/or larger calcifications on CTA had a higher
      risk of developing an MI and/or obstructive CAD within 1 year compared to
      patients without (adjusted RR of 7.51, 95%CI 1.26-73.42, P = 0.001). Patients
      with low-attenuation plaques on CTA had a higher risk of developing an MI and/or
      obstructive CAD within 1 year than patients without (adjusted RR of 2.73, 95%CI
      1.19-8.50, P = 0.021). Presence of carotid calcifications and low-attenuation
      plaques also portended higher sensitivity (100 and 79.17%, respectively) for the
      development of acute MI. Presence of carotid calcifications and low-attenuation
      plaques can predict the risk of developing acute MI and/or obstructive CAD within
      12-months. Given their high sensitivity, their absence can reliably exclude 12
      month events.

PMID- 27866278
TI  - Risk of acute myeloid leukemia and myelodysplastic syndrome among older women
      receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern
      Cooperative Group Trials (Alliance A151511).
AB  - PURPOSE: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome
      (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance
      for Clinical Trials in Oncology trials with >90 months of follow-up in order to
      better characterize the risk for AML/MDS in older patients receiving
      anthracyclines. METHODS: We used multivariable Cox regression to examine factors
      associated with AML/MDS, adjusting for age (>=65 vs. <65 years; separately for
      >=70 vs. <70 years), race/ethnicity, insurance, performance status, and
      anthracycline receipt. We also examined the effect of cyclophosphamide, the
      interaction of anthracycline and age, and outcomes for those developing AML/MDS.
      RESULTS: On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741,
      7290 received anthracyclines; 15% were in the age >=65 and 7% were >=70. Overall,
      47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events
      occurred within 5 years of study registration. Among those age >=65 and >=70, 0.8
      and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted
      analyses, older age and anthracycline receipt were significantly associated with
      AML/MDS (adjusted hazard ratio [HR] for age >=65 [vs. <65] = 3.13, 95% confidence
      interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] =
      5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline
      use. Deaths occurred in 70% of those developing AML/MDS. CONCLUSIONS: We observed
      an increased risk for AML/MDS for older patients and those receiving
      anthracyclines, though these events were rare. Our results help inform
      discussions surrounding anticipated toxicities of adjuvant chemotherapy in older
      patients.

PMID- 27866281
TI  - Reversible lesion involving the splenium of the corpus callosum caused by
      phenytoin sodium withdrawal.

PMID- 27866280
TI  - Proteasome-mediated degradation of tyrosine hydroxylase triggered by its
      phosphorylation: a new question as to the intracellular location at which the
      degradation occurs.
AB  - Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine
      biosynthesis, and its stability is a fundamental factor to maintain the level of
      the catecholamines in cells. However, the intracellular stability of TH
      determined by the degradation remains unknown; although the TH molecule
      phosphorylated at its Ser19 was observed in the nucleus, and the phosphorylation
      suspected to trigger its proteasome-mediated degradation. Computer-assisted
      analysis using the cNLS Mapper program predicted that two sequences of nuclear
      localization signals (NLS) exist in the N-terminus of TH molecule containing the
      phosphorylation sites Ser19, Ser31, and Ser40 (Pro9-Arg38 and Lys12-Ile42): the
      NLS scores indicated that TH could become localized in both nucleus and
      cytoplasm. Moreover, inhibition of the importin alpha/beta-mediated nuclear
      import pathway increased the level of TH phosphorylated at its Ser19 in PC12D
      cells. The results suggest that TH might be imported to nucleus from cytoplasm to
      be degraded. Recent studies revealed that proteasomes predominantly exist in the
      nucleus rather than in the cytoplasm to degrade the nuclear proteins related to
      cell-cycle progression, gene expression, DNA damage, and DNA repair. Therefore,
      these studies suggest that the relationship between the phosphorylation and the
      nuclear localization of the TH molecule should be a matter of focus to understand
      the mechanism of proteasome-mediated degradation of the enzyme as a first
      priority.

PMID- 27866282
TI  - Transfer to inpatient rehabilitation facilities after neurological admission.

PMID- 27866283
TI  - Learning curves of theta/beta neurofeedback in children with ADHD.
AB  - : Neurofeedback is widely applied as non-pharmacological intervention aimed at
      reducing symptoms of ADHD, even though efficacy has not been unequivocally
      established. Neuronal changes during the neurofeedback intervention that resemble
      learning can provide crucial evidence for the feasibility and specificity of this
      intervention. A total of 38 children (aged between 7 and 13 years) with a DSM-IV
      TR diagnosis of ADHD, completed on average 29 sessions of theta (4-8 Hz)/beta (13
      20 Hz) neurofeedback training. Dependent variables included training-related
      measures as well as theta and beta power during baseline and training runs for
      each session. Learning effects were analyzed both within and between sessions. To
      further specify findings, individual learning curves were explored and correlated
      with behavioral changes in ADHD symptoms. Over the course of the training, there
      was a linear increase in participants' mean training level, highest obtained
      training level and the number of earned credits (range b = 0.059, -0.750, p <
      0.001). Theta remained unchanged over the course of the training, while beta
      activity increased linearly within training sessions (b = 0.004, 95% CI = [0.0013
      0.0067], p = 0.005) and over the course of the intervention (b = 0.0052, 95% CI =
      [0.0039-0.0065], p < 0.001). In contrast to the group analyses, significant
      individual learning curves were found for both theta and beta over the course of
      the intervention in 39 and 53%, respectively. Individual learning curves were not
      significantly correlated with behavioral changes. This study shows that children
      with ADHD can gain control over EEG states during neurofeedback, although a lack
      of behavioral correlates may indicate insufficient transfer to daily functioning,
      or to confounding reinforcement of electromyographic activity. CLINICAL TRIALS
      REGISTRATION: This trial is registered at the US National Institutes of Health
      (ClinicalTrials.gov, ref. no: NCT01363544);
      https://clinicaltrials.gov/show/NCT01363544 .

PMID- 27866285
TI  - A Power Calculator for the Classical Twin Design.
AB  - Power is a ubiquitous, though often overlooked, component of any statistical
      analyses. Almost every funding agency and institutional review board requires
      that some sort of power analysis is conducted prior to data collection. While
      there are several excellent on line power calculators for independent
      observations, twin studies pose unique challenges that are not incorporated into
      these algorithms. The goal of the current manuscript is to outline a general
      method for calculating power in twin studies, and to provide functions to allow
      researchers to easily conduct power analyses for a range of common twin models.
      Several scenarios are discussed to demonstrate the importance of various factors
      that influence the power within the classical twin design and to serve as
      examples for the provided functions.

PMID- 27866284
TI  - A syntenic locus on buffalo chromosome 20: novel genomic hotspot for miRNAs
      involved in follicular-luteal transition.
AB  - The developmental reorganization of ovarian follicular granulosa cells (GC)
      during follicular maturation, ovulation, and luteinization require a well
      controlled regulation of dynamic gene expression profiles. Recently, microRNAs
      (miRNAs) were found to be key players of ovarian follicular dynamics. The current
      study aimed to understand the miRNA regulatory role in follicular-luteal
      transition by characterizing the miRNA profile through miRNA-seq at different
      follicular (small, medium, and large) and luteal (early, mid, and late) stages in
      Indian water buffaloes, mono-ovulatory animals like humans. A total of 517 miRNAs
      were identified in follicular granulosa cells (GC) and corpus luteum (CL)
      together. Among them, 2 unique and 40 novel miRNAs were in GC; 15 unique and 45
      novel miRNAs were in CL. Among the remaining 415 annotated common miRNAs between
      GC and CL, 43 have showed significant (p < 0.05) differential expression between
      GC and CL. Particularly, 39 and 4 miRNAs showed higher expression in CL and GC,
      respectively, with respect to each other. Genome mapping analysis revealed that
      71.7% of differential miRNAs having higher expression in CL compared to GC, and
      93% of the unique miRNAs in CL were mapped to a short chromosomal region of 0.7
      Mb (67.4 to 68.1 Mb) on chromosome 21 of cows which is syntenic to the buffalo
      chromosome 20. Clustering of all these miRNAs at this locus suggests it as a
      chromosomal hotspot for miRNAs involved in follicular-luteal transition,
      especially for CL physiological functions.

PMID- 27866286
TI  - Social learning across species: horses (Equus caballus) learn from humans by
      observation.
AB  - This study examines whether horses can learn by observing humans, given that they
      identify individual humans and orientate on the focus of human attention. We
      tested 24 horses aged between 3 and 12. Twelve horses were tested on whether they
      would learn to open a feeding apparatus by observing a familiar person. The other
      12 were controls and received exactly the same experimental procedure, but
      without a demonstration of how to operate the apparatus. More horses from the
      group with demonstration (8/12) reached the learning criterion of opening the
      feeder twenty times consecutively than horses from the control group (2/12), and
      younger horses seemed to reach the criterion more quickly. Horses not reaching
      the learning criteria approached the human experimenters more often than those
      that did. The results demonstrate that horses learn socially across species, in
      this case from humans.

PMID- 27866287
TI  - Examining the gastric cancer survival gap between Asians and whites in the United
      States.
AB  - BACKGROUND: Globally, Asian countries bear a disproportionate gastric cancer
      burden. Asian Americans, the fastest growing minority population in the US, have
      higher gastric cancer survival than non-Hispanic whites (NHWs) despite higher
      incidence. Benefitting from uniform cancer registry standards within the US, we
      examine for the first time the heterogeneity in the Asian American population,
      which may elucidate the causes of these disparities. METHODS: SEER gastric cancer
      data from 2000 to 2012 were used to calculate 5-year survival estimates for NHWs
      and the six largest Asian ethnicities. Multivariate analyses were performed to
      identify critical prognostic factors and survival disparities between Asian
      groups and NHWs. RESULTS: We analyzed 33,313 NHW and 8473 Asian gastric cancer
      cases. All Asian groups had significantly higher 5-year survival than NHWs, at
      29.8%. Among Asians, Koreans and Vietnamese had the highest and lowest survival,
      at 45.4% and 35.7%, respectively. The Korean survival advantage was largely
      attributable to relatively high proportions of localized stage and low
      proportions of cardia tumors. After adjusting for major prognostic factors, the
      survival disadvantage of NHWs, while attenuated, remained significant in
      comparison to all Asian groups (HR: 1.33, 95% CI: 1.24-1.43; reference: Korean).
      The survival disparities within the Asian groups vanished with adjustment.
      CONCLUSIONS: This study characterizes distinctive gastric cancer survival
      patterns among the six major Asian groups and NHWs in the US. The favorable
      survival for Koreans is largely attributable to specific clinical factors,
      particularly stage at diagnosis. The causes of the survival disadvantage for NHWs
      remain elusive.

PMID- 27866289
TI  - Echocardiographic findings in asymptomatic systemic lupus erythematosus patients.
AB  - The aim of this study is to use transthoracic echocardiographic (TTE) imaging
      methods to identify cardiac dysfunction in asymptomatic systemic lupus
      erythematosus (SLE) patients and to determine the association between
      echocardiographic findings and serology. This is a prospective cross-sectional
      study where 50 patients with confirmed diagnoses of SLE were recruited from
      rheumatology outpatient clinics. Clinical and serological evaluation to confirm
      the diagnosis of lupus was done in all patients. Fifty SLE patients, 46 (92%)
      females and 4 (8%) males, were recruited. Anti-double-stranded DNA (Anti-dsDNA),
      anticardiolipin, lupus anticoagulant, and anti-beta2-glycoproteins were positive
      in 52.1, 32.6, 13.3, and 15.6%, respectively. Transthoracic echocardiogram
      revealed mitral regurgitation in 16 patients (32%), pericardial effusion in16
      patients (32%), aortic regurgitation in five patients (10%), and tricuspid
      regurgitation in 10 patients (20%). Eleven patients had left ventricular
      hypertrophy (22%), and eight patients had ventricular systolic dysfunction (16%).
      Only four patients had ventricular diastolic dysfunction (8%). A significant
      association between mitral and tricuspid valve regurgitation and positive anti
      dsDNA (p < 0.018, p < 0.006, respectively) was found. Positive anticardiolipin
      antibodies, lupus anticoagulant, and anti-beta 2 glycoprotein antibodies were
      also associated with mitral valve regurgitation (p values 0.044, 0.006, and
      0.023), respectively. Active disease assessed by Systemic Lupus Erythematosus
      Disease Activity Index (SLEDAI) was found to be associated with increased risk of
      mitral valvular leaflet thickening (p value 0.028). Performing regular
      transthoracic echocardiogram in asymptomatic SLE patients is important for early
      detection and appropriate treatment of cardiac lesions. Clinically quiescent but
      serologically active disease and presence of antiphospholipid antibodies were
      associated with structural heart abnormalities.

PMID- 27866290
TI  - Efficient oxidation of N-protected tryptophan and tryptophanyl-dipeptides by in
      situ generated dimethyldioxirane provides hexahydropyrroloindoline-containing
      synthons suitable for peptide synthesis and subsequent tryptathionylation.
AB  - A series of hydroxypyrroloindoline (Hpi) containing dipeptides along with the
      corresponding monomeric Hpi-alpha-amino acid (Hpi-2-carboxylate), were prepared
      by reacting a series of N alpha-protected-tryptophans in aqueous or biphasic
      [water/cyclopentyl methyl ether (CPME)] solutions containing Oxone(r) (potassium
      peroxymonosulfate) and acetone. This procedure avoids the tedious distillation of
      unstable dimethyldioxirane (DMDO), which is commonly used to oxidize indoles.
      Monomers N alpha-Boc-Hpi-OH and N alpha-Fmoc-Hpi-OH were readily incorporated by
      solid-phase peptide synthesis (SPPS) into a peptide containing a cysteine; in
      trifluoroacetic acid (TFA), the Hpi underwent intramolecular dehydrative
      condensation with the cysteine thiol to afford the anticipated tryptathionine
      crosslink. This eco- and user-friendly oxidative methodology greatly simplifies
      the synthesis of Hpi derivatives while enabling the synthesis of tryptathionine
      crosslinks characteristic of phalloidin and amanitin, two potent peptide toxins
      of present interest.

PMID- 27866288
TI  - Impact of Sexual Trauma on HIV Care Engagement: Perspectives of Female Patients
      with Trauma Histories in Cape Town, South Africa.
AB  - South African women have disproportionately high rates of both sexual trauma and
      HIV. To understand how sexual trauma impacts HIV care engagement, we conducted in
      depth qualitative interviews with 15 HIV-infected women with sexual trauma
      histories, recruited from a public clinic in Cape Town. Interviews explored
      trauma narratives, coping behaviors and care engagement, and transcripts were
      analyzed using a constant comparison method. Participants reported multiple and
      complex traumas across their lifetimes. Sexual trauma hindered HIV care
      engagement, especially immediately following HIV diagnosis, and there were
      indications that sexual trauma may interfere with future care engagement, via
      traumatic stress symptoms including avoidance. Disclosure of sexual trauma was
      limited; no women had disclosed to an HIV provider. Routine screening for sexual
      trauma in HIV care settings may help to identify individuals at risk of poor care
      engagement. Efficacious treatments are needed to address the psychological and
      behavioral sequelae of trauma.

PMID- 27866291
TI  - Japanese contribution to the field of sentinel lymph node biopsy for breast
      cancer patients: introduction to invited articles.

PMID- 27866292
TI  - Small reductions in corolla size and pollen: ovule ratio, but no changes in
      flower shape in selfing populations of the North American Arabidopsis lyrata.
AB  - The shift from outcrossing to selfing is often accompanied by striking changes in
      floral morphology towards a "selfing syndrome", which is characterized by flowers
      with reduction in size, pollen: ovule (P/O) ratio, and herkogamy. This study aims
      to test whether such changes have occurred in the North American Arabidopsis
      lyrata, which is of particular interest because of the relatively recent
      transitions to selfing in this system. Flower size, flower shape, herkogamy
      levels, P/O ratio, and floral integration of six self-incompatible (outcrossing)
      and six self-compatible (selfing) populations of A. lyrata were measured in a
      common environment using conventional and geometric morphometrics methods.
      Although selfers had on average 9.2% smaller corollas, 8.4% longer pistils, and
      21.5% lower P/O ratios than outcrossers, there were no differences in shape,
      floral integration, and herkogamy between outcrossing and selfing populations.
      Moreover, most variation in floral traits was explained by population genetic
      background rather than by mating system. We conclude that selfing populations in
      A. lyrata have not evolved a selfing syndrome.

PMID- 27866294
TI  - Renal paratransplant hernia revealed: a review of the literature.
AB  - BACKGROUND: Renal paratransplant hernia (RPH) is an uncommon variant of internal
      hernias developed in renal transplant recipients. The aim of this review is to
      meticulously present and analyze all data coming mainly from case reports or
      short-case studies on this very uncommon surgical entity. MATERIALS AND METHODS:
      The MEDLINE/PubMed database was searched for publications with the medical
      subject heading ''renal paratransplant hernia''. All the references from the
      identified articles were searched for relevant information. The end date of the
      literature search was set to March 2016. RESULTS: Our search revealed five
      publications, three short clinical series (three cases each) and two case
      reports. The total number of cases retrieved was 11. RPH should be considered as
      an iatrogenic surgical complication. The incidence is around 0.45%. CONCLUSIONS:
      RPH is a relatively uncommon but potentially fatal complication after renal
      transplantation, and its non-specific symptoms may lead to misdiagnosis.
      Physician awareness, prompt diagnosis, and early surgical intervention are
      critical. In addition, meticulous surgical technique during transplantation may
      help avoid this complication.

PMID- 27866293
TI  - The efficacy of laparoscopic intracorporeal linear suture technique as a strategy
      for reducing recurrences in pediatric inguinal hernia.
AB  - PURPOSE: Pediatric laparoscopic herniorrhaphy has rare complications, but
      recurrence might occur. The purpose of this manuscript is to evaluate the
      efficacy of linear suture technique of laparoscopic pediatric herniorrhaphy in
      reducing recurrences. METHODS: Laparoscopic surgery was performed on 2223
      pediatric patients (under 10 years old) from September 2012 to December 2014 in
      Damsoyu Hospital, Seoul, Republic of Korea. The causes of recurrence were
      investigated case by case. The patients were categorized into two groups
      according to the suture method used in closing the hernia orifice: Group 1 (purse
      string suture, 1009 patients) and Group 2 (linear suture, 1214 patients).
      RESULTS: There were 1413 (63.6%) male and 810 (36.4%) female patients. Mean age
      was 30.5 +/- 29.2 months. A significantly higher proportion of male patients,
      contralateral patent processus vaginalis, and less proportion of recurrence were
      observed in Group 2. There were ten cases of recurrence in Group 1 because the
      internal ring suture could not endure the tension. One recurrence occurred in
      Group 2. The suture technique and age were found to be a significant risk factor
      for recurrence. Linear suture technique had a lower recurrence rate (odds ratio =
      0.07, with 95% confidence interval 0.01-0.53, and p = 0.004). CONCLUSIONS: Purse
      string suture technique causes significantly higher occurrence of hernia
      recurrences than linear suture technique. Linear suture technique can reduce
      recurrence by increasing the endurance to tension around the internal ring by
      distributing pressure to a wider area along the linear suture line. Linear suture
      technique can effectively reduce recurrence in pediatric inguinal herniorrhaphy.

PMID- 27866295
TI  - Characterization of a neutral recombinant xylanase from Thermoactinospora rubra
      YIM 77501T.
AB  - A xylanase gene (TrXyn10) from Thermoactinospora rubra YIM 77501T was cloned and
      expressed in Escherichia coli. The amino acid sequence displayed 78% homology
      with Microbispora mesophila xylanase (WP_062413927.1). The recombinant xylanase
      (TrXyn10), with MW 46.1 kDa, could hydrolyse beechwood, birchwood and oatspelt
      xylan. Based on the sequence, enzymatic properties and tertiary structure of the
      protein, TrXyn10 belongs to glycoside hydrolase family 10 (GH10). The optimal pH
      and temperature for the recombinant enzyme were determined to be 7.0 and 55 
      degrees C, respectively. TrXyn10 was stable over a wide pH range, and it retained
      more than 45% of the total activity at pH 6.0-12.0 for 12 h. In addition, the
      activity was greatly promoted, by approximately 200% of the initial activity,
      after incubation at pH 6.0 and 7.0 for 12 h. Based on enzymatic properties and
      product analysis, we showed that TrXyn10 is a neutral endoxylanase.

PMID- 27866296
TI  - Intranasal Curcumin Inhibits Pulmonary Fibrosis by Modulating Matrix
      Metalloproteinase-9 (MMP-9) in Ovalbumin-Induced Chronic Asthma.
AB  - Pulmonary fibrosis is associated with irreversible, or partially reversible,
      airflow obstruction and ultimately unresponsiveness to asthma therapies such as
      corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been
      found effective in allergic asthma. To study the effect of intranasal curcumin on
      airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice
      were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21
      (after sensitization) for 5 weeks (twice/week). Curcumin (intranasal) was
      administered during the OVA aerosol challenge. Mice exposed to OVA developed
      inflammation dominated by eosinophils which lead to fibrosis and airway
      remodeling. Intranasal administration of curcumin significantly inhibited airway
      inflammation and pulmonary fibrosis, where MMP-9 activities were decreased along
      with alpha-smooth muscle actin (alpha-SMA), MMP-9, TIMP-1, and eotaxin
      expressions. These results suggest that intranasal curcumin regulates airway
      inflammation and remodeling in chronic asthma.

PMID- 27866298
TI  - Radiation-induced osteosarcoma after Gamma Knife surgery for vestibular
      schwannoma: a case report and literature review.
AB  - We present a rare case of radiation-induced osteosarcoma following Gamma Knife(r)
      surgery (GKS) for a vestibular schwannoma (VS). A 49-year-old female with
      sporadic VS underwent GKS. Serial follow-up imaging showed that the tumor size
      decreased. Six years after GKS, magnetic resonance imaging demonstrated regrowth
      of the tumor. The tumor was removed via the retrosigmoid approach. Interestingly,
      the final pathology report confirmed osteosarcoma arising in schwannoma with
      direct transition (osteosarcoma component: 90 %, schwannoma component: 10 %). The
      osteosarcoma was considered to be a radiation-induced malignancy. The possibility
      of this rare complication should be explained to the patient before GKS, and the
      patient should be screened periodically after GKS.

PMID- 27866297
TI  - NPS2143 Inhibits MUC5AC and Proinflammatory Mediators in Cigarette Smoke Extract
      (CSE)-Stimulated Human Airway Epithelial Cells.
AB  - Mucus overproduction is a fundamental hallmark of COPD that is caused by exposure
      to cigarette smoke. MUC5AC is one of the main mucin genes expressed in the
      respiratory epithelium, and its transcriptional upregulation often correlates
      with increased mucus secretion. Calcium-sensing receptor (CaSR) antagonists have
      been reported to possess anti-inflammatory effects. The purpose of the present
      study was to investigate the protective role of NPS2143, a selective CaSR
      antagonist on cigarette smoke extract (CSE)-stimulated NCI-H292 mucoepidermoid
      human lung cells. Treatment of NPS2143 significantly inhibited the expression of
      MUC5AC in CSE-stimulated H292 cells. NPS2143 reduced the expression of MMP-9 in
      CSE-stimulated H292 cells. NPS2143 also decreased the release of proinflammatory
      cytokines such as IL-6 and TNF-alpha in CSE-stimulated H292 cells. Furthermore,
      NPS2143 attenuated the activation of MAPKs (JNK, p38, and ERK) and inhibited the
      nuclear translocation of NF-kappaB in CSE-stimulated H292 cells. These results
      indicate that NPS2143 had a therapeutic potential in COPD.

PMID- 27866299
TI  - Localization and dynamics of the anticarcinogenic curcumin with GM1 and other
      miceller assemblies.
AB  - Structural transitions involving shape changes play an important role in cellular
      physiology and enhance the bioavailability of the natural food like curcumin in
      surfactant aggregates. In this work, we have studied the localization, dynamics
      and stability of curcumin in various miceller assemblies using a combination of
      absorbance and fluorescence spectroscopic approaches. The measurements of
      absorption and fluorescence spectra of curcumin revealed that the nature of
      interactions of ionic and nonionic surfactants and the glycosphingolipid, GM1
      with curcumin is significantly different with surfactant concentrations. At low
      concentrations of SDS and the GM1 the head group of SDS and GM1 binds to the
      central beta-diketone group of curcumin to form SDS-curcumin or GM1-curcumin
      complexes. At high concentrations, both formed micelles with curcumin completely
      solubilized inside. Cucurmin is solubilized in the stern layer of SDS micelles.
      Compared to spherical micelles, rod shaped micelles allow more curcumin to bind
      through hydrophobic interactions indicated by higher absorption and fluorescence,
      enhanced partition coefficient and stability. Whereas curcumin associates with
      GM1 micelles with lower partition coefficient, solubility and remain closer to
      aqueous phase decreasing its bioavailability and stability. While cucurmin is
      solubilized in the palisade layer of deoxycholate and octyl glucopyranoside
      micelles through the alkyl chains providing more hydrophobic microenvironment to
      curcumin with enhanced stability and bioavailability. Graphical abstract
      Schematic diagram of the two different types of detergent micelles and larger GM1
      micelles.

PMID- 27866300
TI  - Endoscopic Management of Biliary Leaks and Strictures After Living Donor Liver
      Transplantation: Optimizing Techniques for Successful Management.
AB  - BACKGROUND AND AIMS: Biliary complications (BCs) occur in up to 40% of living
      donor liver transplant (LDLT) recipients. The aim of this study was to evaluate
      the efficacy of endoscopic therapy in the management of LDLT-related BCs.
      METHODS: A retrospective study of 100 LDLT recipients at a single transplant
      center over a 9-year period was conducted. BC was defined as a biliary leak
      and/or a stricture. Patient records were used to identify time to diagnosis, type
      of intervention, and time to resolution. RESULTS: BCs occurred in 46 (46%)
      patients; median follow-up was 4.6 years (range 5 days-9.3 years); and median
      time to diagnosis was 37.5 days (range 1 day-3.5 years). BCs were classified as a
      leak in 6 (6%), stricture in 22 (22%), and a leak + stricture in 18 (18%). ERCP
      was the initial treatment modality in 43/46 (93%) patients and was completed in
      42/43 (98%). Three (6.5%) patients with a leak underwent surgery as the primary
      treatment approach. The median time to resolution of BCs was 91.5 days (range 21
      367). Thirteen patients had a recurrence which was managed with endoscopic
      therapy alone. CONCLUSIONS: Endoscopic therapy was successful in almost all
      patients (98%) and ERCP alone resulted in successful treatment in a higher
      proportion of patients (93%) than traditionally reported. Advanced endoscopic
      techniques obviate the need for PTC and/or surgery and allow successful
      management in almost all LDLT recipients presenting with BC and in patients with
      recurrence of strictures.

PMID- 27866303
TI  - Anesthetic technique and cancer recurrence in oncologic surgery: unraveling the
      puzzle.
AB  - Surgery/anesthetic technique-stimulated immunosuppression in the perioperative
      period might cause an increase in cancer-related mortality. Whether anesthetic
      technique can affect the outcomes of cancer patients remains inconclusive. This
      review discusses data from the available literature on anesthetic techniques
      applied in oncologic surgery, the long-term outcomes of anesthetic technique, and
      their relation to survival and cancer recurrence. Searches of the PubMed database
      up to June 30, 2016, were conducted to identify publications with the terms
      "anesthetic technique and cancer recurrence," "regional anesthesia and cancer
      recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and
      immunosuppression," and "anesthetic technique and oncologic surgery."
      Surgery/anesthesia-stimulated activation of the hypothalamic-pituitary-adrenal
      (HPA) axis and the sympathetic nervous system (SNS) provides immunosuppression
      through several soluble factors. Volatile anesthetics and opioids suppress cell
      mediated immunity (CMI) and promote the proliferation of cancer cells and
      angiogenesis, whereas propofol does not suppress CMI and inhibits tumor
      angiogenesis. Regional anesthesia (RA) protects CMI and diminishes the surgical
      neuroendocrine stress response by blocking afferent neural transmission that
      stimulates the HPA axis and SNS, decreasing the requirement for opioids and
      volatile anesthetics and thereby decreasing cancer recurrence. Preclinical and
      retrospective studies highlight a potential benefit of anesthetic technique in
      reducing cancer-related mortality and recurrence by attenuating immunosuppression
      following surgical treatment in patients with specific types of cancer. Several
      well-planned, prospective, randomized controlled trials (RCTs) are underway that
      may provide more conclusive and definitive results regarding the benefits of
      anesthetic technique on survival in oncologic surgery.

PMID- 27866301
TI  - Longitudinal Profiles of Girls' Irritable, Defiant and Antagonistic Oppositional
      Symptoms: Evidence for Group Based Differences in Symptom Severity.
AB  - Three subdimensions of ODD symptoms have been proposed -angry/irritable (IR),
      argumentative/defiant (DF) and antagonism (AN). This study tested whether
      longitudinal symptom trajectories could be identified by these subdimensions.
      Group-based trajectory analysis was used to identify developmental trajectories
      of IR, DF and AN symptoms. Multi-group trajectory analysis was then used to
      identify how subdimension trajectories were linked together over time. Data were
      drawn from the Pittsburgh Girls Study (PGS; N = 2450), an urban community sample
      of girls between the ages of five--eight at baseline. We included five waves of
      annual data across ages five-13 to model trajectories. Three trajectories were
      identified for each ODD subdimension: DF and AN were characterized by high,
      medium and low severity groups; IR was characterized by low, medium stable, and
      high increasing groups. Multi-trajectory analysis confirmed these subdimensions
      were best linked together based on symptom severity. We did not identify girls'
      trajectory groups that were characterized predominantly by a particular
      subdimension of ODD symptoms. Membership in more severe symptom groups was
      significantly associated with worse outcomes five years later. In childhood and
      early adolescence girls with high levels of ODD symptoms can be identified, and
      these youth are characterized by a persistently elevated profile of IR, DF and AN
      symptoms. Further studies in clinical samples are required to examine the ICD-10
      proposal that ODD with irritability is a distinct or more severe form of ODD.

PMID- 27866302
TI  - Expression analysis of Dickkopf-related protein 3 (Dkk3) suggests its pleiotropic
      roles for a secretory glycoprotein in adult mouse.
AB  - Dickkopf-related protein 3 (Dkk3) is the third member of the Dkk gene family and
      identical to the gene, whose expression was reduced in immortalized cells.
      Therefore, its another name is reduced expression in immortalized cells. Since
      the intratumoral introduction of Dkk3 inhibits tumor growth in mouse models of
      cancers, Dkk3 is likely a tumor suppressor gene. However, the functions of Dkk3
      in vivo remain unclear. As the first step to decipher the physiological roles of
      this gene, we examined the expression pattern of Dkk3 in various tissues from
      adult mice. In situ hybridization showed that Dkk3 mRNA was detected in the
      brain, retina, heart, gastrointestinal tract, adrenal glands, thymus, prostate
      glands, seminal vesicles, testes, and ovaries in a regionally specific manner.
      Furthermore, we raised anti-mouse Dkk3 antibody and performed
      immunohistochemistry. Cytoplasmic localization of Dkk3 protein was observed in
      the cells of the adrenal medulla, while Dkk3 immunoreactivity was observed in the
      lumen of the stomach and intestine, implying that the Dkk3 protein may be
      secreted into the lumen of the gastrointestinal tract. These results suggest that
      Dkk3 has pleiotropic roles for a secretory glycoprotein that acts primarily in
      the gastrointestinal tract, thymus, endocrine and reproductive organs of the
      mouse.

PMID- 27866304
TI  - Cell lineage determinants as regulators of breast cancer metastasis.
AB  - The mammary epithelium is organized in a hierarchy of mammary stem cells (MaSCs),
      progenitors, and differentiated cells. The development and homeostasis of mammary
      gland are tightly controlled by a complex network of cell lineage regulators.
      These determinants of cellular hierarchy are frequently deregulated in breast
      tumor cells and closely associated with cancer progression and metastasis. They
      also contribute to the diversity of breast cancer subtypes and their distinct
      metastatic patterns. Cell fate regulators that normally promote stem/progenitor
      activities can serve as drivers for epithelial-mesenchymal transition and
      metastasis whereas regulators that promote terminal differentiation generally
      suppress metastasis. In this review, we discuss how some of the key factors
      function in normal mammary lineage determination and how these processes are
      hijacked by tumor cells to enhance metastasis. Understanding the molecular
      connections between normal development and cancer metastasis will enable the
      development of more specific and effective therapeutic approaches targeting
      metastatic tumor cells.

PMID- 27866305
TI  - Mental Health Status of Double Minority Adolescents: Findings from National Cross
      Sectional Health Surveys.
AB  - Little population-based work has been published about the mental health of
      adolescents with both sexual/gender (SG) and ethnic minority (i.e. double
      minority) status. This study aimed to provide an overview on their mental health.
      Analysis of data from a total of 17,607 high school students from New Zealand's
      2007 and 2012 cross-sectional nationally representative Adolescent Health
      Surveys, including a total of 1306 (7.4%) SG minority participants, of whom 581
      (3.3%) were also an ethnic minority. SG minority status, minority ethnicity, and
      female sex were associated with higher mental distress and poorer well-being.
      Generally speaking, double minority students reported poorer mental health than
      SG majority students of the same ethnicity, but reported better mental health
      than SG minority New Zealand European students. Explanations and future
      directions for research were suggested to further explore how double minority
      students negotiate mental health in the context of their communities/cultures in
      New Zealand.

PMID- 27866306
TI  - Low Dose of Bisphenol A Activates NF-kappaB/IL-6 Signals to Increase Malignancy
      of Neuroblastoma Cells.
AB  - Bisphenol A (BPA) can accumulate in the human body and promote the progression of
      various cancers. However, its role in the development of neuroblastoma (NB) is
      largely unknown. Our present study revealed that nanomolar concentrations of BPA
      can significantly increase the proliferation, migration and invasion of NB SH
      SY5Y and SiMa cells, further evidenced by the upregulation of human proliferating
      cell nuclear antigen, Bcl-2, vimentin and fibronectin. Real-time PCR and ELISA
      results suggested that nanomolar BPA can increase the expression of interleukin-6
      (IL-6), but had no effect on the expression of IL-2, IL-8, IL-10 or IL-12. The
      neutralization antibody of IL-6 can abolish BPA-induced proliferation and
      invasion of NB cells. The inhibitor of NF-kappaB (BAY 11-7082), but not PD98059
      (PD, ERK1/2 inhibitor) or LY294002 (LY, PI3 K/Akt inhibitor), attenuated BPA
      induced IL-6 expression and cell proliferation and invasion. In addition, BPA
      treatment also rapidly increased the phosphorylation of p65 since treatment for 5
      min. Collectively, our data revealed that nanomolar BPA can trigger the
      malignancy of NB cells via activation of NF-kappaB/IL-6 signals, suggesting that
      more attention should be paid to the potential health risks of daily BPA intake.

PMID- 27866307
TI  - Explicating the Conditions Under Which Multilevel Multiple Imputation Mitigates
      Bias Resulting from Random Coefficient-Dependent Missing Longitudinal Data.
AB  - Random coefficient-dependent (RCD) missingness is a non-ignorable mechanism
      through which missing data can arise in longitudinal designs. RCD, for which we
      cannot test, is a problematic form of missingness that occurs if subject-specific
      random effects correlate with propensity for missingness or dropout. Particularly
      when covariate missingness is a problem, investigators typically handle missing
      longitudinal data by using single-level multiple imputation procedures
      implemented with long-format data, which ignores within-person dependency
      entirely, or implemented with wide-format (i.e., multivariate) data, which
      ignores some aspects of within-person dependency. When either of these standard
      approaches to handling missing longitudinal data is used, RCD missingness leads
      to parameter bias and incorrect inference. We explain why multilevel multiple
      imputation (MMI) should alleviate bias induced by a RCD missing data mechanism
      under conditions that contribute to stronger determinacy of random coefficients.
      We evaluate our hypothesis with a simulation study. Three design factors are
      considered: intraclass correlation (ICC; ranging from .25 to .75), number of
      waves (ranging from 4 to 8), and percent of missing data (ranging from 20 to
      50%). We find that MMI greatly outperforms the single-level wide-format
      (multivariate) method for imputation under a RCD mechanism. For the MMI analyses,
      bias was most alleviated when the ICC is high, there were more waves of data, and
      when there was less missing data. Practical recommendations for handling
      longitudinal missing data are suggested.

PMID- 27866308
TI  - Establishing a Mathematical Equations and Improving the Production of L-tert
      Leucine by Uniform Design and Regression Analysis.
AB  - L-tert-Leucine (L-Tle) and its derivatives are extensively used as crucial
      building blocks for chiral auxiliaries, pharmaceutically active ingredients, and
      ligands. Combining with formate dehydrogenase (FDH) for regenerating the
      expensive coenzyme NADH, leucine dehydrogenase (LeuDH) is continually used for
      synthesizing L-Tle from alpha-keto acid. A multilevel factorial experimental
      design was executed for research of this system. In this work, an efficient
      optimization method for improving the productivity of L-Tle was developed. And
      the mathematical model between different fermentation conditions and L-Tle yield
      was also determined in the form of the equation by using uniform design and
      regression analysis. The multivariate regression equation was conveniently
      implemented in water, with a space time yield of 505.9 g L-1 day-1 and an
      enantiomeric excess value of >99 %. These results demonstrated that this method
      might become an ideal protocol for industrial production of chiral compounds and
      unnatural amino acids such as chiral drug intermediates.

PMID- 27866309
TI  - Osteoporosis in patients with diabetes after kidney transplantation.
AB  - Preexisting diabetes increases risk of fractures after kidney transplantation
      (KT). However, little is known about mechanisms and prevention of increased
      fragility in these patients. Pathophysiology of osteoporosis after KT is complex
      and characterized by high prevalence of adynamic bone disease. Despite high
      prevalence of preexisting diabetes in KT recipients, diabetes patients were
      underrepresented in the studies that explored mechanisms and treatments of
      osteoporosis after KT. Therefore, caution should be exercised before considering
      conventional fracture prevention strategies in this unique group of patients.
      Many traditional osteoporosis medications reduce bone turnover and, hence, can be
      ineffective or even harmful in diabetic patients after KT. Contrary to
      predictions, evidence from the studies conducted in mostly non-diabetic subjects
      demonstrated that bisphosphonates failed to reduce fracture rates after KT.
      Therefore, bisphosphonates use should be limited in diabetic patients until more
      evidence supporting their post-transplant efficacy is available. We recommend the
      following strategies that may help reduce fracture risk in diabetes subjects
      after KT such as adequate management of calcium, parathyroid hormone, and vitamin
      D levels, optimization of glycemic control, use of steroid-sparing
      immunosuppressive regimens, and fall prevention.

PMID- 27866311
TI  - Unforced Revision in Processing Relative Clause Association Ambiguity in
      Japanese: Evidence Against Revision as Last Resort.
AB  - The current study tackles a long standing question of whether comprehenders
      perform structural revision when it is not forced by grammar or not. Using an eye
      tracking reading paradigm, we addressed this issue by making use of global
      structural ambiguity in Japanese. Our results show that comprehenders initially
      associate a relative clause with the first potential head noun and that they
      revise this analysis when the second noun is lexico-semantically possible as the
      relative clause head, but do not when it is impossible. The results are
      incompatible with the Revision as Last Resort hypothesis. Instead, they support
      the parsing with unforced revision that is immediately sensitive to lexical
      properties. We argue that our results cannot be accounted for by serial modular
      processing models but that they can be explained by ranked-parallel interactive
      processing models. Furthermore, we propose that head-finality is a key factor
      involved in the availability of unforced revision.

PMID- 27866310
TI  - Prediction of difficult laryngoscopy using spirometry: a pilot study.
AB  - Prediction of difficult laryngoscopy is still the uncovered secret of anesthetic
      practice. This pilot study is aimed to assess the efficacy of spirometry
      measurements in predicting difficult laryngoscopy compared with conventional
      airway assessment techniques. We enrolled 202 adults, ages 18-40 years, with an
      American Society of Anaesthesiologists score of I or II, scheduled for elective
      surgery and undergoing general anesthesia. Spirometry was used for lung capacity
      measurements before the operation. The Mallampati classification, neck
      circumference, sternomental distance, thyromental distance, maximum mouth-opening
      measurement, and upper lip bite test of the subjects were measured. During
      intubation, the Cormack-Lehane grade was recorded. Spearman's correlation
      analysis was used to define the linearity between spirometry outputs and airway
      measurements. Receiver operating curves were drawn to discriminate the predictive
      features of the significant values. The thyromental distance showed a higher
      correlation with forced inspiratory vital capacity (rho = 0.420, P < 0.001). In a
      multivariate linear regression model, all spirometry measurements revealed that
      forced inspiratory vital capacity (beta = -2.050, P = 0.022) was the significant
      predictor for difficult laryngoscopy. The area under the curve for forced
      inspiratory vital capacity with a cut-off value of 3.1950 L while using
      thyromental distance as difficult laryngoscopy indicator is 0.754 and forced
      inspiratory vital capacity showed a sensitivity of 0.718 and specificity of 0.714
      with a positive likelihood ratio of 2.5104 and negative likelihood ratio of
      0.3949. Forced inspiratory vital capacity showed a close association with the
      prediction of difficult laryngoscopy.

PMID- 27866312
TI  - Transgenic citrus expressing synthesized cecropin B genes in the phloem exhibits
      decreased susceptibility to Huanglongbing.
AB  - KEY MESSAGE: Expression of synthesized cecropin B genes in the citrus phloem,
      where Candidatus Liberibacter asiaticus resides, significantly decreased host
      susceptibility to Huanglongbing. Huanglongbing (HLB), associated with Candidatus
      Liberibacter asiaticus bacteria, is the most destructive disease of citrus
      worldwide. All of the commercial sweet orange cultivars lack resistance to this
      disease. The cationic lytic peptide cecropin B, isolated from the Chinese tasar
      moth (Antheraea pernyi), has been shown to effectively eliminate bacteria. In
      this study, we demonstrated that transgenic citrus (Citrus sinensis Osbeck)
      expressing the cecropin B gene specifically in the phloem had a decreased
      susceptibility to HLB. Three plant codon-optimized synthetic cecropin B genes,
      which were designed to secrete the cecropin B peptide into three specific sites,
      the extracellular space, the cytoplasm, and the endoplasmic reticulum, were
      constructed. Under the control of the selected phloem-specific promoter GRP1.8,
      these constructs were transferred into the citrus genome. All of the cecropin B
      genes were efficiently expressed in the phloem of transgenic plants. Over more
      than a year of evaluation, the transgenic lines exhibited reduced disease
      severity. Bacterial populations in transgenic lines were significantly lower than
      in the controls. Two lines, in which bacterial populations were significantly
      lower than in others, showed no visible symptoms. Thus, we demonstrated the
      potential application of the phloem-specific expression of an antimicrobial
      peptide gene to protect citrus plants from HLB.

PMID- 27866313
TI  - Two MYB-related transcription factors play opposite roles in sugar signaling in
      Arabidopsis.
AB  - KEY MESSAGE: Sugar regulation of gene expression has profound effects at all
      stages of the plant life cycle. Although regulation at the transcriptional level
      is one of the most prominent mechanisms by which gene expression is regulated,
      only a few transcription factors have been identified and demonstrated to be
      involved in the regulation of sugar-regulated gene expression. OsMYBS1, an R1/2
      type MYB transcription factor, has been demonstrated to be involved in sugar- and
      hormone-regulated alpha-amylase gene expression in rice. Arabidopsis contains two
      OsMYBS1 homologs. In the present study, we investigate MYBS1 and MYBS2 in sugar
      signaling in Arabidopsis. Our results indicate that MYBS1 and MYBS2 play opposite
      roles in regulating glucose and ABA signaling in Arabidopsis during seed
      germination and early seedling development. MYB proteins have been classified
      into four subfamilies: R2R3-MYB, R1/2-MYB, 3R-MYB, and 4R-MYB. An R1/2-type MYB
      transcription factor, OsMYBS1, has been demonstrated to be involved in sugar- and
      hormone-regulated alpha-amylase genes expression in rice. In this study, two
      genes homologous to OsMYBS1, MYBS1 and MYBS2, were investigated in Arabidopsis.
      Subcellular localization analysis showed that MYBS1 and MYBS2 were localized in
      the nucleus. Rice embryo transient expression assays indicated that both MYBS1
      and MYBS2 could recognize the sugar response element, TA-box, in the promoter and
      induced promoter activity. mybs1 mutant exhibited hypersensitivity to glucose,
      whereas mybs2 seedlings were hyposensitive to it. MYBS1 and MYBS2 are involved in
      the control of glucose-responsive gene expression, as the mybs1 mutant displayed
      increased expression of a hexokinase gene (HXK1), chlorophyll a/b-binding protein
      gene (CAB1), ADP-glucose pyrophosphorylase gene (APL3), and chalcone synthase
      gene (CHS), whereas the mybs2 mutant exhibited decreased expression of these
      genes. mybs1 also showed an enhanced response to abscisic acid (ABA) in the seed
      germination and seedling growth stages, while mybs2 showed reduced responses. The
      ABA biosynthesis inhibitor fluridone rescued the mybs1 glucose-hypersensitive
      phenotype. Moreover, the mRNA levels of three ABA biosynthesis genes, ABA1,
      NCED9, and AAO3, and three ABA signaling genes, ABI3, ABI4, and ABI5, were
      increased upon glucose treatment of mybs1 seedlings, but were decreased in mybs2
      seedlings. These results indicate that MYBS1 and MYBS2 play opposite roles in
      regulating glucose and ABA signaling in Arabidopsis during seed germination and
      early seedling development.

PMID- 27866314
TI  - Factors associated with health-related quality of life (HRQOL) in adults with
      short stature skeletal dysplasias.
AB  - INTRODUCTION: Numerous factors associate with health disparities. The extent to
      which such factors influence health-related quality of life (HRQOL) among adults
      with short stature skeletal dysplasias (SD) is unknown. In an effort to update
      and clarify knowledge about the HRQOL of adults with SD, this study aimed to
      quantify HRQOL scores relative to the American average and assess whether
      specific indicators are associated with lower scores. METHODS: Members (>18
      years) of Little People of America were invited to complete an online survey
      assessing HRQOL using the SF-12 supplemented with indicator-specific questions.
      SF-12 components (Physical Component Summary, PCS; Mental Component Summary, MCS)
      were compared to the standardized national American mean. Scores were divided at
      the median to identify factors associated with lower scores using multivariable
      logistic regression, adjusting for age, gender, race, education, and employment.
      RESULTS: A total of 189 surveys were completed. Mean and median PCS and MCS were
      below the national mean of 50 (p < 0.001). Advancing decade of age corresponded
      to a significant decline in PCS (p < 0.001) but not MCS (p = 0.366). Pain
      prevalence was high (79.4%); however, only 5.9% visited a pain specialist.
      Significant factors for lower PCS included age >40 years (p = 0.020), having
      spondyloepiphyseal dysplasia congenita (SED) or diastrophic dysplasia relative to
      achondroplasia (p = 0.023), pain (p < 0.001), and "partial" versus "full" health
      insurance coverage (p = 0.034). For MCS, significant factors included a lack of
      social support (p = 0.002) and being treated differently/feeling stigmatized by
      health care providers (p = 0.022). CONCLUSIONS: Individuals with SD face
      documented disparities and report lower HRQOL. Further research and interventions
      are needed to modify nuanced factors influencing these results and address the
      high prevalence of pain.

PMID- 27866315
TI  - Does the EQ-5D capture the effects of physical and mental health status on life
      satisfaction among older people? A path analysis approach.
AB  - PURPOSE: To examine the extent to which EQ-5D utility scores capture the effect
      of mental and physical health status on life satisfaction (LS) in older adults.
      METHODS: Retrospective cohort study of 884 patients aged >=70 years from 15
      general practices in Ireland, including medical records, pharmacy claims, and
      self-completion questionnaire. Path analysis was used to evaluate the direct and
      indirect effects of: (1) chronic disease burden (based on medications data); (2)
      activity limitation (basic and instrumental activities of daily living); (3)
      anxiety symptoms and; (4) depressive symptoms (Hospital Anxiety and Depression
      Scale) on LS (Life Satisfaction Index Z), via a utility score based on responses
      to the EQ-5D scale. Utility scores were calculated using UK time trade-off
      utility weights. Covariates included age and socioeconomic status. RESULTS: The
      final path model fitted the data well (goodness of fit chi2 = 7.5, df (7), p =
      0.37). The direct effects of chronic disease burden and disability on LS were not
      statistically significant and were excluded from the final model, indicating that
      EQ-5D score mediated 100% of the total effect on LS. The direct and indirect
      effects of anxiety and depression on LS were statistically significant, but the
      size of the indirect effect was small (4% of the total effect for anxiety and 6%
      of the total effect for depression). CONCLUSION: The EQ-5D does not adequately
      capture the effects of anxiety and depression on LS among older adults,
      suggesting that it may lead to inaccurate assessments of the effectiveness of
      interventions in this cohort.

PMID- 27866316
TI  - Epidemiology of developmental dysplasia of the hip within the UK: refining the
      risk factors.
AB  - PURPOSE: The epidemiology and risk factors for developmental dysplasia of the hip
      (DDH) are still being refined. We investigated the local epidemiology of DDH in
      order to define incidence, identify risk factors, and refine our policy on
      selective ultrasound screening. METHODS: With a cohort study design, data were
      prospectively recorded on all live births in our region from January 1998 to
      December 2008. We compared data on babies treated for DDH with data for all other
      children. Crude odds ratios (ORs) were calculated to identify potential risk
      factors. Logistic regression was then used to control for interactions between
      variables. RESULTS: There were 182 children born with DDH (with a total of 245
      dysplastic hips) and 37,051 without. The incidence was 4.9 per 1000 live births.
      Female sex (adjusted OR 7.2, 95% confidence interval [CI] 4.6-11.2), breech
      presentation (adjusted OR 24.3, 95% CI 13.1-44.9), positive family history
      (adjusted OR 15.9, 95% CI 11.0-22.9) and first or second pregnancy (adjusted OR
      1.8, 95% CI 1.5-2.3) were confirmed as risk factors (p < 0.001). In addition,
      there was an increased risk with vaginal delivery (adjusted OR 2.7, 1.6-4.5, p <
      0.001) and post-maturity (OR 1.7, 1.2-2.4, p < 0.002). CONCLUSIONS: One in 200
      children born within our region requires treatment for DDH. Using both
      established and novel risk factors, we can potentially calculate an individual
      child's risk. Our findings may contribute to the debate regarding selective
      versus universal ultrasound screening. LEVEL OF EVIDENCE: Prognostic Study: Level
      1.

PMID- 27866317
TI  - Spectrofluorimetric and Potentiometric Determination of Acidity Constants of 4
      (4'-Acetyloxy-3'-Methoxybenzylidene)-5-Oxazolone Derivatives.
AB  - 4-(4'-acetyloxy-3'-methoxybenzylidene)-5-oxazolone fluorescent molecules bearing
      four different aryl groups attached to the 2-position of 5-oxazolone ring have
      been investigated by spectrophotometric and potentiometric techniques in solution
      media. The acidity constants (pKa) of the fluorescent molecules were precisely
      determined in acetone, acetonitrile, dimethylformamide and in 1:1 mixture of
      toluene-isopropanol. The studied derivatives were titrated with
      tetrabutylammonium hydroxide and non-aqueous perchloric acid by scanning the
      basic and acidic region of the pH scale. A computerizable derivative method was
      used in order to descript precisely the end point and pKa values. The molecules
      investigated performed well-shaped and stoichiometric potentiometric titration
      curves.

PMID- 27866318
TI  - Pig BVDV-2 non-structural protein (Npro) links to cellular antiviral response in
      vitro.
AB  - In this study, we constructed for the first time a full-length cDNA clone of pig
      original bovine viral diarrhea virus 2 (BVDV-2) strain SH-28, modified the cDNA
      clone (pASH28) for mutant pASHDeltaNpro and derived virus strain vASHDeltaNpro by
      deleting the genomic region encoding the Npro polypeptide, and examined
      significance of protein Npro for antiviral responses in vitro. Data showed that
      Npro-deletion mutant virus vASHDeltaNpro led to significant overexpression of
      oligo adenylate synthetase (OAS), myxovirus-resistant protein 1 (Mx1), and
      ubiquitin-like protein 15 (ISG15). Data also revealed that overexpression of
      Npro, but not NS2 and NS3 proteins, resulted in significant down-regulation of
      OAS, Mx1, and ISG15 production (p <= 0.05) in bovine cells as well as porcine
      cells transfected with Npro recombinant eukaryotic expression plasmids. Npro (but
      not NS2 and NS3) was also found to inhibit poly(IC) from inducing production of
      type I interferon (IFN-I). These results indicated that protein Npro may play
      multiple roles in regulating antiviral response in host cells interfered by pig
      BVDV-2 strain, and provided useful information to understand better the mechanism
      of BVDV-2 persistent infection in pigs.

PMID- 27866319
TI  - Successful Posaconazole Therapy of Disseminated Alternariosis due to Alternaria
      infectoria in a Heart Transplant Recipient.
AB  - We report a case of phaeohyphomycosis caused by Alternaria infectoria in a 61
      year-old heart transplant recipient with multiple skin lesions and pulmonary
      infiltrates. The infection spread via the haematogenous route from the primary
      cutaneous lesions into the lungs. The diagnosis was based on the
      histopathological examination, direct microscopy, skin lesion cultures and
      detection of Alternaria DNA in the bronchoalveolar lavage fluid using molecular
      methods. The treatment consisted of a combination of surgical excision and
      systemic antifungal therapy. Voriconazole was the first agent used but had a weak
      effect. Posaconazole was subsequently used to achieve a successful response. The
      isolate was identified as A. infectoria by sequencing of the rDNA ITS region and
      the partial beta-tubulin gene.

PMID- 27866320
TI  - Protein tyrosine phosphatase 1B inhibitory properties of seco-cucurbitane
      triterpenes obtained from fruiting bodies of Russula lepida.
AB  - The known seco-cucurbitane triterpene, (24E)-3,4-seco-cucurbita-4,24-diene
      3,26,29-trioic acid (1), has been isolated as a potent protein tyrosine
      phosphatase (PTP) 1B inhibitor together with a new analogue, (24E)-3,4-seco
      cucurbita-4,24-diene-3-hydroxy-26,29-dioic acid (2), from the fruiting bodies of
      Russula lepida. Further evaluation of their biological properties against PTPs
      revealed that compound 1 inhibited T-cell PTP activity similarly to PTP1B and
      exhibited moderate selectivity against PTP1B over vaccinia H-1-related
      phosphatase. Moreover, the in vitro growth inhibitory effects of 1 and 2 against
      three human cancer cell lines were examined in order to evaluate cell-based
      efficacy. However, neither 1 nor 2 enhanced insulin-stimulated p-Akt levels at
      non-cytotoxic concentrations.

PMID- 27866321
TI  - Exceptional Symmetry by Genomic Word : A Statistical Analysis.
AB  - Single-strand DNA symmetry is pointed as a universal law observed in the genomes
      from all living organisms. It is a somewhat broadly defined concept, which has
      been refined into some more specific measurable effects. Here we discuss the
      exceptional symmetry effect. Exceptional symmetry is the symmetry effect beyond
      that expected in independence contexts, and it can be measured for each word, for
      each equivalent composition group, or globally, combining the effects of all
      possible words of a given length. Global exceptional symmetry was found in
      several species, but there are genomic words with no exceptional symmetry effect,
      whereas others show a very high exceptional symmetry effect. In this work, we
      discuss a measure to evaluate the exceptional symmetry effect by symmetric word
      pair, and compare it with others. We present a detailed study of the exceptional
      symmetry by symmetric pairs and take the CG content into account. We also
      introduce and discuss the exceptional symmetry profile for the DNA of each
      organism, and we perform a multiple comparison for 31 genomes: 7 viruses; 5
      archaea; 5 bacteria; 14 eukaryotes.

PMID- 27866322
TI  - Rare Case of an Ancient Craniofacial Osteosarcoma with Probable Surgical
      Intervention.
AB  - Osteosarcoma is the most common primary malignant bone tumor both today and in
      antiquity. Nevertheless, it is a comparatively rare tumor. This paper describes a
      case of a highly aggressive craniofacial lesion from the 11th-12th centuries AD,
      most likely representing osteosarcoma. During the paleopathological study,
      macroscopic, endoscopic, radiological, scanning-electron and light microscopic
      investigations were performed. The skull of the approximately 40-50 year-old
      female revealed several pathological findings. The most impressive macroscopic
      feature was an extensively spiculated periosteal reaction ("sunburst" pattern) in
      combination with a massive bone destruction most likely derived from a highly
      aggressive tumor originating in the ethmoidal area of the medial wall of the
      orbit. The central parts of the lesion showed excessive new and most probably
      neoplastic bone formation indicating an underlying high-grade osteosarcoma. The
      light microscopic examination revealed three different levels of bony structures
      representing different qualities of bone tissues. Besides the mass lesion, signs
      of a healed multiple incomplete trephination of the left parietal bone was
      observed. This case represents a unique example in which the concomitance of a
      tumor and an incomplete trephination could be observed from the skeletal remains
      of an ancient individual. The case opens new considerations as to whether
      surgical interventions, such as incomplete trephination, might have been used
      already in the Middle Ages as a therapeutic approach.

PMID- 27866323
TI  - Measuring Compassion in Healthcare: A Comprehensive and Critical Review.
AB  - BACKGROUND: There is international concern about the lack of compassion in
      healthcare systems. A valid and reliable tool for measuring compassion in
      healthcare systems and educational institutions is required. This comprehensive
      and critical narrative synthesis identified and compared existing measures of
      compassionate care in clinical settings. METHODS: PubMed, MEDLINE, CINAHL and
      PsycINFO databases and grey literature were searched to identify studies that
      report information on instruments that measure compassion or compassionate care
      in clinicians, nurses, healthcare students and patients. Textual qualitative
      descriptions of included studies were prepared. Instruments were evaluated using
      the Evaluating Measures of Patient-Reported Outcomes (EMPRO) tool. RESULTS: Nine
      studies containing information on the Compassion Competence Scale, a self-report
      instrument that measures compassion competence among Korean nurses; the
      Compassion Scale, the Compassionate Care Assessment Tool(c), and the Schwartz
      Center Compassionate Care ScaleTM, patient-reported instruments that measure the
      importance of healthcare provider compassion; the Compassion Practices Scale, an
      instrument that measures organisational support for compassionate care; and
      instruments that measure compassion in educational institutions (instructional
      quality and a Geriatric Attitudes Scale), were included. Each instrument is
      associated with significant limitations. Most only measure certain aspects of
      compassion and lack evidence of adaptability to diverse practice settings. The
      EMPRO of self-report instruments revealed a lack of psychometric information on
      measurement reliability, validity, responsiveness and interpretability,
      respondent, administrative and scoring burden, and use in subpopulations.
      CONCLUSION: The findings of this narrative synthesis identified an unmet need for
      a psychometrically validated instrument that comprehensively measures the
      construct of compassion in healthcare settings.

PMID- 27866324
TI  - Pedicle screw insertion techniques: an update and review of the literature.
AB  - Pedicle screw construct have become one of the most practiced procedure in spinal
      surgery. Despite commonly used, questions remain about their safety especially
      for the thoracic spine and in deformity where difficulty in positioning can lead
      to pedicle breach and adjacent structures injury. Misplacement rates have been
      reported to be from 5 to 41% in the lumbar spine and from 3 to 55% in the
      thoracic spine. Hence, various procedures have been described in order to improve
      pedicle screw insertion accuracy. Aim of this study is to evaluate current
      concepts on pedicle screws placement techniques to better understand recent
      attitude and clarify some doubts when selecting the most proper method.

PMID- 27866325
TI  - Sexually Dimorphic Expression of Reelin in the Brain of a Mouse Model of
      Alzheimer Disease.
AB  - Recent evidence highlights the protective role of reelin against amyloid beta
      (Abeta)-induced synaptic dysfunction and cognitive impairment in Alzheimer
      disease (AD). In this study, exploiting TgCRND8 mice that overexpress a mutant
      form of amyloid beta precursor protein (AbetaPP) and display an early onset of AD
      neuropathological signs, we addressed the question whether changes of reelin
      expression eventually precede the appearance of Abeta-plaques in a sex-dependent
      manner. We show that sex-associated and brain region-specific differences in
      reelin expression appear long before Abeta-plaque formation. However, in spite of
      a downregulation of reelin expression compared to males, TgCRND8 females display
      fewer Abeta-plaques, suggesting that additional factors, other than sex and
      reelin level, influence amyloidosis in this mouse model.

PMID- 27866327
TI  - Mesenchymal Stem Cells Attenuate the Adverse Effects of Immunosuppressive Drugs
      on Distinct T Cell Subopulations.
AB  - Immunosuppressive drugs are widely used to treat undesirable immune reaction,
      however their clinical use is often limited by harmful side effects. The combined
      application of immunosuppressive agents with mesenchymal stem cells (MSCs) offers
      a promising alternative approach that enables the reduction of immunosuppressive
      agent doses and simultaneously maintains or improves the outcome of therapy. The
      present study aimed to determinate the effects of immunosuppressants on
      individual T cell subpopulations and to investigate the efficacy of MSC-based
      treatment combined with immunosuppressive drugs. We tested the effect of five
      widely used immunosuppressants with different action mechanisms: cyclosporine A,
      mycophenolate mofetil, rapamycin, and two glucocorticoids - prednisone and
      dexamethasone in combination with MSCs on mouse CD4+ and CD8+ lymphocyte
      viability and activation, Th17 (RORgammat+), Th1 (T-bet+), Th2 (GATA-3+) and Treg
      (Foxp3+) cell proportion and on the production of corresponding key cytokines (IL
      17, IFNgamma, IL-4 and IL-10). We showed that MSCs modulate the actions of
      immunosuppressants and in combination with immunosuppressive drugs display
      distinct effect on cell activation and balance among different T lymphocytes
      subpopulations and exert a suppressive effect on proinflammatory T cell subsets
      while promoting the functions of anti-inflammatory Treg lymphocytes. The results
      indicated that MSC-based therapy could be a powerful strategy to attenuate the
      negative effects of immunosuppressive drugs on the immune system.

PMID- 27866328
TI  - Histochemical changes of occlusal surface enamel of permanent teeth, where dental
      caries is questionable vs sound enamel surfaces.
AB  - AIM: This in vitro study was to classify questionable for caries occlusal
      surfaces (QCOS) of permanent teeth according to ICDAS codes 1, 2, and 3 and to
      compare them in terms of enamel mineral composition with the areas of sound
      tissue of the same tooth. METHODS: Partially impacted human molars (60) extracted
      for therapeutic reasons with QCOS were used in the study, photographed via a
      polarised light microscope and classified according to the ICDAS II (into codes
      1, 2, or 3). The crowns were embedded in clear self-cured acrylic resin and
      longitudinally sectioned at the levels of the characterised lesions and studied
      by SEM/EDX, to assess enamel mineral composition of the QCOS. Univariate and
      multivariate random effect regressions were used for Ca (wt%), P (wt%), and Ca/P
      (wt%). RESULTS: The EDX analysis indicated changes in the Ca and P contents that
      were more prominent in ICDAS-II code 3 lesions compared to codes 1 and 2 lesions.
      In these lesions, Ca (wt%) and P (wt%) concentrations were significantly
      decreased (p = 0.01) in comparison with sound areas. Ca and P (wt%) contents were
      significantly lower (p = 0.02 and p = 0.01 respectively) for code 3 areas in
      comparison with codes 1 and 2 areas. Significantly higher (p = 0.01) Ca (wt%) and
      P (wt%) contents were found on sound areas compared to the lesion areas.
      CONCLUSIONS: The enamel of occlusal surfaces of permanent teeth with ICDAS 1, 2,
      and 3 lesions was found to have different Ca/P compositions, necessitating
      further investigation on whether these altered surfaces might behave differently
      on etching preparation before fissure sealant placement, compared to sound
      surfaces.

PMID- 27866326
TI  - The Neuroprotective Peptide Poly-Arginine-12 (R12) Reduces Cell Surface Levels of
      NMDA NR2B Receptor Subunit in Cortical Neurons; Investigation into the
      Involvement of Endocytic Mechanisms.
AB  - We have previously reported that cationic poly-arginine and arginine-rich cell
      penetrating peptides display high-level neuroprotection and reduce calcium influx
      following in vitro excitotoxicity, as well as reduce brain injury in animal
      stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the
      NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also
      known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine
      rich peptides reduce glutamate-induced excitotoxic calcium influx. Using cell
      surface biotin protein labeling and western blot analysis, we demonstrated that
      R12 and TAT-NR2B9c significantly reduced cortical neuronal cell surface
      expression of the NMDA receptor subunit NR2B. Chemical endocytic inhibitors used
      individually or in combination prior to glutamate excitotoxicity did not
      significantly affect R12 peptide neuroprotective efficacy. Similarly,
      pretreatment of neurons with enzymes to degrade anionic cell surface
      proteoglycans, heparan sulfate proteoglycan (HSPG), and chondroitin sulfate
      proteoglycan (CSPG), as well as sialic acid residues, did not significantly
      affect peptide neuroprotective efficacy. While the exact mechanisms responsible
      for R12 peptide-mediated NMDA receptor NR2B subunit cell surface downregulation
      were not identified, an endocytic process could not be ruled out. The study
      supports our hypothesis that arginine-rich peptides reduce excitotoxic calcium
      influx by reducing the levels of cell surface ion channels.

PMID- 27866329
TI  - Diffusional behavior and guest conformational analysis of hexadecane-1,16-diol
      and hexadecane in urea crystal model via molecular dynamics simulation approach.
AB  - Diffusion at the atomic or molecular level is a source of many physical,
      chemical, and biological processes taking place in plentiful materials. This work
      is an endeavor toward investigating the diffusional behavior of two different
      type of guests, hexadecane-1,16-diol and hexadecane enclathration in urea tunnel
      architecture, whereby the correlation of the diffusion mechanism with the guest's
      structural and conformational properties is explored. To carry out this study,
      molecular dynamics simulation approach is adopted. It is found that hexadecane
      1,16-diol exhibit slower diffusion with an average diffusion coefficient value
      [Formula: see text], where hexadecane diffuse more rapidly with an average
      diffusion coefficient value [Formula: see text]. It is also observed that the
      structural properties influence the guest's travel distance and torsion angle
      distribution of the trans and gauche conformational proportion. Furthermore, the
      observed high energy barrier accounted for hexadecane-1,16-diol and low energy
      barrier for hexadecane along urea tunnel systems was analyzed. The comparison of
      our obtained results are in close agreement with the available experimental
      measurements, i.e., gauche proportion properties between two different guest
      molecules correlate well with Raman spectroscopy investigation on alpha,omega
      dihalogenoalkane/urea inclusion compounds. Our calculations also successfully
      endorse the structure-property relation between the two systems.

PMID- 27866330
TI  - Human gut microbiota: the links with dementia development.
AB  - Dementia is a comprehensive category of brain diseases that is great enough to
      affect a person's daily functioning. The most common type of dementia is
      Alzheimer's disease, which makes most of cases. New researches indicate that
      gastrointestinal tract microbiota are directly linked to dementia pathogenesis
      through triggering metabolic diseases and low-grade inflammation progress. A
      novel strategy is proposed for the management of these disorders and as an
      adjuvant for psychiatric treatment of dementia and other related diseases through
      modulation of the microbiota (e.g. with the use of probiotics).

PMID- 27866331
TI  - Photoreceptor degeneration by intravitreal injection of N-methyl-N-nitrosourea
      (MNU) in rabbits: a pilot study.
AB  - BACKGROUND: Pilot study on the attempt to induce selective photoreceptor
      degeneration in the rabbit eye by intravitreal injection of MNU, facing the
      difficulties of the evaluation of retinal degeneration by different in-vivo and
      in-vitro methods in such a large eye animal model. METHODS: Eight pigmented
      Chinchilla Bastard rabbits were injected intravitreally with MNU (1 * 1mg/kg body
      weight (BW), 1 * 2mg/kg BW, 3 * 3mg/kg BW, 1 * 4mg/kg BW, 1 * 6mg/kg BW, and 1 *
      DMSO + PBS as control). One, 2, and 3 weeks after injection, the effects on the
      rabbit retina were examined in vivo using clinical observation (macroscopic
      images, funduscopy, weighing of the animals), measurement of intraocular pressure
      (IOP), full-field Electroretinography (ffERG), and spectral-domain Optical
      Coherence Tomography (sd-OCT). After 3 weeks follow-up, blood samples were taken
      to evaluate the general health status of the animals, and immunohistochemistry
      (IH) was performed on sections obtained from six different regions throughout the
      whole retina to evaluate MNU effects in more detail. RESULTS: It was difficult to
      observe the effects of MNU on retinal structure by OCT in vivo. Only the temporal
      quadrant of the retina could be visualized. Therefore, it was indispensible to
      evaluate the effects of MNU on the retina in vitro by examining six areas of the
      retina using immunohistochemistry. Furthermore, immunohistochemistry plays a
      decisive role to evaluate the effects on retinal cells other than photoreceptors
      while in H&E staining, namely the cell count of the ONL can be observed. The
      results obtained in vivo and in vitro in this study mainly follow the results of
      a previous study in mice. The low doses of MNU (1, 2 mg/kg BW) had no effects on
      retinal function and morphology, while high doses (4, 6 mg/kg BW) led to retinal
      changes in combination with significant side-effects (e.g., cataractous changes).
      Injection of 3 mg/kg BW MNU induced selective photoreceptor degeneration.
      However, the degree of degeneration varied between different parts of the same
      retina and between retinae of different animals. In two of three animals, a
      complete loss of ERG potentials was observed. Negative effects on the
      contralateral eye or on general welfare of the animal were never observed.
      CONCLUSIONS: In rabbits, the intravitreal injection of 3 mg/kg BW MNU leads to
      selective but inhomogeneous photoreceptor degeneration.

PMID- 27866332
TI  - Decreased proteinase A excretion by strengthening its vacuolar sorting and
      weakening its constitutive secretion in Saccharomyces cerevisiae.
AB  - Proteinase A (PrA), encoded by PEP4 gene, is detrimental to beer foam stability.
      There are two transport pathways for the new synthesized PrA in yeast, sorting to
      the vacuole normally, or excreting out of the cells under stress conditions. They
      were designated as the Golgi-to-vacuole pathway and the constitutive secretory
      pathway, respectively. To reduce PrA excretion in some new way instead of its
      coding gene deletion, which had a negative effect on cell metabolism and beer
      fermentation, we modified the PrA transport based on these above two pathways. In
      the Golgi-to-vacuole pathway, after the verification that Vps10p is the dominant
      sorting receptor for PrA Golgi-to-vacuolar transportation by VPS10 deletion,
      VPS10 was then overexpressed. Furthermore, SEC5, encoding exocyst complexes'
      central subunit (Sec5p) in the constitutive secretory pathway, was deleted. The
      results show that PrA activity in the broth fermented with WGV10 (VPS10
      overexpressing strain) and W?SEC5 (SEC5 deletion strain) was lowered by 76.96 and
      32.39%, compared with the parental strain W303-1A, at the end of main
      fermentation. There are negligible changes in fermentation performance between
      W?SEC5 and W303-1A, whereas, surprisingly, WGV10 had a significantly improved
      fermentation performance compared with W303-1A. WGV10 has an increased growth
      rate, resulting in higher biomass and faster fermentation speed; finally, wort
      fermentation is performed thoroughly. The results show that the biomass
      production of WGV10 is always higher than that of W?SEC5 and W303-1A at all
      stages of fermentation, and that ethanol production of WGV10 is 1.41-fold higher
      than that of W303-1A. Obviously, VPS10 overexpression is beneficial for yeast and
      is a more promising method for reduction of PrA excretion.

PMID- 27866333
TI  - Strain engineering and process optimization for enhancing the production of a
      thermostable steryl glucosidase in Escherichia coli.
AB  - Biodiesels produced from transesterification of vegetable oils have a major
      problem in quality due to the presence of precipitates, which are mostly composed
      of steryl glucosides (SGs). We have recently described an enzymatic method for
      the efficient removal of SGs from biodiesel, based on the activity of a
      thermostable beta-glycosidase from Thermococcus litoralis. In the present work,
      we describe the development of an Escherichia coli-based expression system and a
      high cell density fermentation process. Strain and process engineering include
      the assessment of different promoters to drive the expression of a codon
      optimized gene, the co-expression of molecular chaperones and the development of
      a high cell density fermentation process. A 200-fold increase in the production
      titers was achieved, which directly impacts on the costs of the industrial
      process for treating biodiesel.

PMID- 27866334
TI  - Growth and wax ester production of an Acinetobacter baylyi ADP1 mutant deficient
      in exopolysaccharide capsule synthesis.
AB  - Acinetobacter baylyi ADP1 naturally produces wax esters that could be used as a
      raw material in industrial applications. We attempted to improve wax ester yield
      of A. baylyi ADP1 by removing rmlA, a gene involved in exopolysaccharide
      production. Growth rate, biomass formation and wax ester yield on 4
      hydroxybenzoate were not affected, but the rmlA - strain grew slower on acetate,
      while reaching similar biomass and wax ester yield. The rmlA - cells had
      malformed shape and large size and grew poorly on glucose without expression of
      the gene for pyruvate kinase (pykF) from Escherichia coli. The pykF-expressing
      rmlA - strain had similar growth rate, lowered biomass formation and improved wax
      ester production on glucose as compared to the wild-type strain expressing pykF.
      Cultivation of the pykF-expressing rmlA - strain on an elevated glucose
      concentration in a medium supplemented with amino acids resulted in doubled molar
      wax ester yield and acetate production.

PMID- 27866336
TI  - The role of clinical pharmacists in treatment adherence: fast impact in
      suppression of chronic myeloid leukemia development and symptoms.
AB  - PURPOSE: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease,
      accounting for 15 to 20% of leukemias, with an incidence of one to two
      cases/100,000 inhabitants. In Brazil, the estimated incidence of leukemia is six
      cases/100,000 men and 4.28 cases/100,000 women. CML is characterized by the
      presence of the Philadelphia chromosome. At present, three types of tyrosine
      kinase inhibitors (TKI) are administered to treat CML patients in the Brazilian
      public national health system (NHS), called the Unified Health System (in
      Portuguese, "Sistema Unico de Saude", SUS). Such treatments are only effective if
      patients adhere to strict dosage regimens; protocol improvements that increase
      patient adherence to treatment would have economic and health benefits for
      overburdened health care systems. Here, pharmacist-monitored treatment is
      assessed. METHODS: In our study, we applied two questionnaires, one to assess the
      adherence to pharmacological treatment and another to assess the quality of life.
      All patients studied (n = 23) were diagnosed with CML at a local hospital in
      "Espirito Santo" State, the "Hospital Evangelico Vila Velha" (HEVV). RESULTS:
      Treatment adherence was significantly higher in pharmacist-monitored patients
      than in nonmonitored patients (p = 0.0135). The quality of life of CML patients
      was also analyzed, indicating that monitored patients had a lower number of
      symptoms/complaints during treatment periods than nonmonitored patients. Finally,
      improved treatment adherence also translated into better clinical conditions,
      particularly during the early stage of treatment (e.g., the first 4 months).
      CONCLUSIONS: The intervention of a clinical pharmacist is significant to obtain
      positive clinical results. Therefore, it is recommended that this protocol be
      included in the standard NHS treatment protocol CML patient outcomes to reduce
      the indirect and recurring costs to the health care system caused by
      nonadherence.

PMID- 27866338
TI  - Reflections on Serving Remote Mountain Communities: Mobile Hospitals and Women's
      and Children's Health Care in Northern Haiti.
AB  - In 2003 Alyans Sante Borgne's (ASB) conducted the first week-long mobile hospital
      in Molas, a poor mountain community a 10-h walk from the main hospital in the
      town of Borgne in North Haiti. ASB is a partnership between Haiti Outreach-Pwoje
      Espwa (H.O.P.E.), a US-based NGO, and Haiti's Ministry of Health. The paper
      reflects on this first experience and the evolution of an indigenous model of
      health care delivery, Sante Nan Lakou (SNL)/Health at the Extended Family Level,
      a model that prioritizes the needs of patients over those of the institution. It
      highlights the challenges of providing quality care to a much neglected segment
      of our population and documents the impact of this event for the community and
      for ASB. Lessons learned during that week shaped ASB's response to the root
      causes of women and children's poor health in the commune of Borgne. The response
      is articulated in a holistic grassroots program called Sante/Health,
      Edikasyon/Education, Ekonomi/Economy for Fanm/Women (SEE Fanm). SEE Fanm is a
      constellation of programs and initiatives that together brings quality care to
      women and seeks to empower them to take charge of their health and wellbeing and,
      by extension, that of their families and communities.

PMID- 27866337
TI  - Mental and physical health correlates among family caregivers of patients with
      newly-diagnosed incurable cancer: a hierarchical linear regression analysis.
AB  - PURPOSE: Caregiver, relational, and patient factors have been associated with the
      health of family members and friends providing care to patients with early-stage
      cancer. Little research has examined whether findings extend to family caregivers
      of patients with incurable cancer, who experience unique and substantial
      caregiving burdens. We examined correlates of mental and physical health among
      caregivers of patients with newly-diagnosed incurable lung or non-colorectal
      gastrointestinal cancer. METHODS: At baseline for a trial of early palliative
      care, caregivers of participating patients (N = 275) reported their mental and
      physical health (Medical Outcome Survey-Short Form-36); patients reported their
      quality of life (Functional Assessment of Cancer Therapy-General). Analyses used
      hierarchical linear regression with two-tailed significance tests. RESULTS:
      Caregivers' mental health was worse than the U.S. national population (M = 44.31,
      p < .001), yet their physical health was better (M = 56.20, p < .001).
      Hierarchical regression analyses testing caregiver, relational, and patient
      factors simultaneously revealed that younger (B = 0.31, p = .001), spousal
      caregivers (B = -8.70, p = .003), who cared for patients reporting low emotional
      well-being (B = 0.51, p = .01) reported worse mental health; older (B = -0.17, p
      = .01) caregivers with low educational attainment (B = 4.36, p < .001) who cared
      for patients reporting low social well-being (B = 0.35, p = .05) reported worse
      physical health. CONCLUSIONS: In this large sample of family caregivers of
      patients with incurable cancer, caregiver demographics, relational factors, and
      patient-specific factors were all related to caregiver mental health, while
      caregiver demographics were primarily associated with caregiver physical health.
      These findings help identify characteristics of family caregivers at highest risk
      of poor mental and physical health who may benefit from greater supportive care.

PMID- 27866339
TI  - Recurrent TP53 missense mutation in cancer patients of Arab descent.
AB  - Hereditary cancer comprises more than 10% of all breast cancer cases.
      Identification of germinal mutations enables the initiation of a preventive
      program that can include early detection or preventive treatment and may also
      have a major impact on cancer therapy. Several recurrent mutations were
      identified in the BRCA1/2 genes in Jewish populations however, in other ethnic
      groups in Israel, no recurrent mutations were identified to date. Our group
      established panel sequencing in cancer patients to identify recurrent, founder,
      and new mutations in the heterogeneous and diverse populations in Israel, We
      evaluated five breast cancer patients of Arab descent diagnosed with cancer
      before the age of 50 years and identified the previously described TP53 mutation,
      c.541C>T, R181C (rs587782596), in two women from unrelated Arab families. The two
      probands were diagnosed with breast cancer at a young age (27 and 34 years) and
      had significant family history spanning a wide range of tumors (breast cancer
      (BC), papillary thyroid cancer, glioblastoma multiform (GBM), colon cancer and
      leukemia). The R181C variant is expected to disrupt p53 at the ASPP2 binding
      domain but not the DNA binding domain and is defined by Clinvar as likely
      pathogenic and in HGMD as disease mutation. We further tested 85 unrelated Arab
      cancer patients and father of a BC carrier patient for TP53 c.541C>T using a real
      time polymerase chain reaction (RT-PCR) approach and identified four additional
      carriers, two with BC one with lung cancer, and the father of a BC carrier
      patient, diagnosed with GBM. Another carrier suffering from BC was identified
      using a Myriad panel, suggesting a recurrent mutation in this population with a
      frequency of 5/42 (11.9%) of our selected BC patients. We suggest testing Arab
      women with a breast cancer at a young age, Arab patients with multiple
      malignancies, or with suggestive family history for TP53 c.541C>T.

PMID- 27866340
TI  - The hereditary nature of small cell carcinoma of the ovary, hypercalcemic type:
      two new familial cases.
AB  - Small cell carcinoma of the ovary, hypercalcemic type, (SCCOHT) is the most
      common undifferentiated ovarian cancer in women aged under 40 years. SCCOHT is a
      monogenic disease, characterized by germline and somatic SMARCA4 mutations.
      Recent studies have stressed its morphological and clinical similarity to
      malignant rhabdoid tumours, which are usually caused by mutations in the related
      gene, SMARCB1. While familial tumours are rare, the incidence of germline
      mutations is relatively high, with up to 43% of SCCOHTs and 35% of rhabdoid
      tumours caused by germline mutations in SMARCA4 and SMARCB1, respectively. We
      report two new familial cases of SCCOHT. Affected members in both families and
      the associated tumours were found to carry SMARCA4 germline and somatic
      mutations, respectively, leading to loss of SMARCA4 protein expression in the
      tumours. Despite the rarity of familial SCCOHT, the high incidence of germline
      mutations is important to note, as without a family history of the disease, the
      hereditary nature of SCCOHT may be missed, especially if the mutation was
      inherited from the father or acquired de novo. The similarity between SCCOHT and
      rhabdoid tumours should be recognized, as infant carriers of SMARCA4 mutations
      may be at risk for these tumours in addition to SCCOHT.

PMID- 27866341
TI  - The role of the P2X7 receptor in murine cutaneous leishmaniasis: aspects of
      inflammation and parasite control.
AB  - Leishmania amazonensis is the etiological agent of diffuse cutaneous
      leishmaniasis. The immunopathology of leishmaniasis caused by L. amazonensis
      infection is dependent on the pathogenic role of effector CD4+ T cells.
      Purinergic signalling has been implicated in resistance to infection by different
      intracellular parasites. In this study, we evaluated the role of the P2X7
      receptor in modulating the immune response and susceptibility to infection by L.
      amazonensis. We found that P2X7-deficient mice are more susceptible to L.
      amazonensis infection than wild-type (WT) mice. P2X7 deletion resulted in
      increased lesion size and parasite load. Our histological analysis showed an
      increase in cell infiltration in infected footpads of P2X7-deficient mice.
      Analysis of the cytokine profile in footpad homogenates showed increased levels
      of IFN-gamma and decreased TGF-beta production in P2X7-deficient mice, suggesting
      an exaggerated pro-inflammatory response. In addition, we observed that CD4+ and
      CD8+ T cells from infected P2X7-deficient mice exhibit a higher proliferative
      capacity than infected WT mice. These data suggest that P2X7 receptor plays a key
      role in parasite control by regulating T effector cells and inflammation during
      L. amazonensis infection.

PMID- 27866342
TI  - Phototoxicity and chronic toxicity of methyl paraben and 1,2-hexanediol in
      Daphnia magna.
AB  - Parabens are used as antimicrobial preservatives in consumer products. Exposure
      to methylparaben (MP) has been associated with adverse health outcomes,
      therefore, an alternative compound, 1,2-hexanediol (1,2-H), has been applied for
      cosmetics. In the present study, the phototoxicity of MP and 1,2-H, as well as
      the toxic effect caused by chronic exposure, were investigated using Daphnia
      magna. The 48 h acute toxicity tests with D. magna were conducted under indoor or
      ultraviolet (UV) light irradiation conditions, i.e., exposure to 4 h/d sunlight.
      Changes in the transcription of genes related to oxidative stress were determined
      in D. magna juveniles, to investigate the underlying mechanism of phototoxicity.
      The 21 d chronic toxicity tests of MP and 1,2-H were performed under indoor light
      irradiation. Exposure to MP under environmental level of UV light was more
      detrimental to D. magna. Transcripts of catalase and glutathione-S-transferase
      genes in D. magna was significantly increased by co-exposure to MP and UV light.
      After 21 d of chronic exposure to MP and 1,2-H, the reproduction no-observed
      effect concentrations for D. magna were 1 and >10 mg/L, respectively. The present
      study showed that exposure to UV could magnify the toxicity of MP on daphnids.
      Although acute and chronic toxicities of 1,2-H were generally lower than those of
      MP, its effects on other aquatic organisms should not be ignored. Further studies
      are needed to identify other mechanisms of MP phototoxicity.

PMID- 27866343
TI  - Maternal transfer of trace elements in the Atlantic horseshoe crab (Limulus
      polyphemus).
AB  - The maternal transfer of trace elements is a process by which offspring may
      accumulate trace elements from their maternal parent. Although maternal transfer
      has been assessed in many vertebrates, there is little understanding of this
      process in invertebrate species. This study investigated the maternal transfer of
      13 trace elements (Ag, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn) in
      Atlantic horseshoe crab (Limulus polyphemus) eggs and compared concentrations to
      those in adult leg and gill tissue. For the majority of individuals, all trace
      elements were transferred, with the exception of Cr, from the female to the eggs.
      The greatest concentrations on average transferred to egg tissue were Zn (140
      ug/g), Cu (47.8 ug/g), and Fe (38.6 ug/g) for essential elements and As (10.9
      ug/g) and Ag (1.23 ug/g) for nonessential elements. For elements that were
      maternally transferred, correlation analyses were run to assess if the
      concentration in the eggs were similar to that of adult tissue that is completely
      internalized (leg) or a boundary to the external environment (gill). Positive
      correlations between egg and leg tissue were found for As, Hg, Se, Mn, Pb, and
      Ni. Mercury, Mn, Ni, and Se were the only elements correlated between egg and
      gill tissue. Although, many trace elements were in low concentration in the eggs,
      we speculate that the higher transfer of essential elements is related to their
      potential benefit during early development versus nonessential trace elements,
      which are known to be toxic. We conclude that maternal transfer as a source of
      trace elements to horseshoe crabs should not be overlooked and warrants further
      investigation.

PMID- 27866344
TI  - Development of a fast curing tissue adhesive for meniscus tear repair.
AB  - Isocyanate-terminated adhesive amphiphilic block copolymers are attractive
      materials to treat meniscus tears due to their tuneable mechanical properties and
      good adhesive characteristics. However, a drawback of this class of materials is
      their relatively long curing time. In this study, we evaluate the use of an amine
      cross-linker and addition of catalysts as two strategies to accelerate the curing
      rates of a recently developed biodegradable reactive isocyanate-terminated hyper
      branched adhesive block copolymer prepared from polyethylene glycol (PEG),
      trimethylene carbonate, citric acid and hexamethylene diisocyanate. The curing
      kinetics of the hyper-branched adhesive alone and in combination with different
      concentrations of spermidine solutions, and after addition of 2,2
      dimorpholinodiethylether (DMDEE) or 1,4-diazabicyclo [2.2.2] octane (DABCO) were
      determined using FTIR. Additionally, lap-shear adhesion tests using all
      compositions at various time points were performed. The two most promising
      compositions of the fast curing adhesives were evaluated in a meniscus bucket
      handle lesion model and their performance was compared with that of fibrin glue.
      The results showed that addition of both spermidine and catalysts to the adhesive
      copolymer can accelerate the curing rate and that firm adhesion can already be
      achieved after 2 h. The adhesive strength to meniscus tissue of 3.2-3.7 N was
      considerably higher for the newly developed compositions than for fibrin glue
      (0.3 N). The proposed combination of an adhesive component and a cross-linking
      component or catalyst is a promising way to accelerate curing rates of isocyanate
      terminated tissue adhesives.

PMID- 27866345
TI  - Comparison of rabbit rib defect regeneration with and without graft.
AB  - Rib segment, as one of the most widely used autologous boneresources for bone
      repair, is commonly isolated with an empty left in the defect. Although defective
      rib repair is thought to be unnecessary traditionally, it's of vital importance
      actually to promote rib regeneration for patients with better postoperative
      recovery and higher life quality. Comparative investigations on rabbit rib bone
      regeneration with and without graft were reported in this article. A segmental
      defect was performed on the 8th rib of 4-month-old male New Zealand rabbits. The
      mineralized collagen bone graft (MC) was implanted into the defect and evaluated
      for up to 12 weeks. The rib bone repair was investigated by using X-ray at 4, 8
      and 12 weeks and histological examinations at 12 weeks after surgery, which
      showed a higher bone remodeling activity in the groups with MC implantation in
      comparison with blank control group, especially at the early stage of remodeling.

PMID- 27866346
TI  - Comparing the effects of an acute bout of physical exercise with an acute bout of
      interactive mental and physical exercise on electrophysiology and executive
      functioning in younger and older adults.
AB  - BACKGROUND: Physical exercise has been shown to improve cognitive and neural
      functioning in older adults. AIMS AND METHODS: The current study compared the
      effects of an acute bout of physical exercise with a bout of interactive mental
      and physical exercise (i.e., "exergaming") on executive (Stroop) task performance
      and event-related potential (ERP) amplitudes in younger and older adults.
      RESULTS: Results revealed enhanced executive task performance in younger and
      older adults after exercise, with no differences in performance between exercise
      conditions. Stroop (RT) performance in older adults improved more than in younger
      adults from pre- to post-exercise. A significant increase in EEG amplitude from
      pre- to post-exercise was found at the Cz site from 320 to 700 ms post-stimulus
      for both younger and older adults, with older adults demonstrating a larger
      Stroop interference effect. While younger adults exhibited overall greater EEG
      amplitudes than older adults, they showed no differences between congruent and
      incongruent trials (i.e., minimal interference). Compared to peers with higher
      BMI (body mass index), older adults with lower BMI showed a greater reduction in
      Stroop interference effects from pre- to post-exercise. DISCUSSION AND
      CONCLUSIONS: The beneficial effects of an acute bout of physical exercise on
      cognitive and neural functioning in younger and older adults were confirmed, with
      no difference between standard exercise and exergaming. Findings suggest that
      BMI, sometimes used as a proxy for fitness level, may modulate benefits that
      older adults derive from an acute bout of exercise. Findings have implications
      for future research that seeks to investigate unique effects of exergaming when
      compared to standard physical exercise.

PMID- 27866347
TI  - Effect of low-intensity resistance training with heat stress on the HSP72,
      anabolic hormones, muscle size, and strength in elderly women.
AB  - BACKGROUND: Several recent studies have reported that heat stress stimulates the
      activation of heat shock protein 72 (HSP72), leading to an increase in muscle
      synthesis. Some studies suggested that low-intensity resistance training combined
      with heat stress could improve muscle size and strength. AIM: This study aimed to
      identify the effect of low-intensity resistance training with heat stress over 12
      weeks on the HSP72, anabolic hormones, muscle size, and strength in elderly
      women. METHODS: The subjects were physically healthy women of 65-75 years, who
      were randomly assigned to one of three groups: a low-intensity resistance
      training with heating sheet group (HRT group, n = 8), a moderate-intensity
      resistance training (RT group, n = 6), and a heating sheet group (HEAT group, n =
      7). Computed tomography scans, 1-repetition maximum (1RM), and blood samples were
      taken pre- and post-training. RESULTS: The HSP72 did not vary significantly
      between the different groups and times. The IGF-1 and 1RM had significantly
      increased in all three groups after the training (respectively, p < 0.05).
      Moreover, the cross-sectional area (CSA) of the quadriceps showed a significantly
      greater increase in the HRT group than in the HEAT group (p < 0.05). CONCLUSIONS:
      We found that low-intensity training with heat stress stimulated the anabolic
      hormones of elderly women, improving their muscle strength and hypertrophy. We
      believe that low-intensity training with heat stress is an effective way to
      prevent muscle atrophy and to improve muscle strength in elderly women.

PMID- 27866348
TI  - Attentional Differences in a Driving Hazard Perception Task in Adults with Autism
      Spectrum Disorders.
AB  - The current study explored attentional processing of social and non-social
      stimuli in ASD within the context of a driving hazard perception task.
      Participants watched videos of road scenes and detected hazards while their eye
      movements were recorded. Although individuals with ASD demonstrated relatively
      good detection of driving hazards, they were slower to orient to hazards. Greater
      attentional capture in the time preceding the hazards' onset was associated with
      lower verbal IQ. The findings suggest that individuals with ASD may distribute
      and direct their attention differently when identifying driving hazards.

PMID- 27866349
TI  - The Emergent Literacy Skills of Preschool Children with Autism Spectrum Disorder.
AB  - A high percentage of school-age students with autism spectrum disorder (ASD) have
      reading comprehension difficulties leading to academic disadvantage. These
      difficulties may be related to differences in children's emergent literacy
      development in the preschool years. In this study, we examined the relationship
      between emergent literacy skills, broader cognitive and language ability, autism
      severity, and home literacy environment factors in 57 preschoolers with ASD. The
      children showed strengths in code-related emergent literacy skills such as
      alphabet knowledge, but significant difficulties with meaning-related emergent
      literacy skills. There was a significant relationship between meaning-related
      skills, autism severity, general oral language skills, and nonverbal cognition.
      Identification of these meaning-related precursors will guide the targets for
      early intervention to help ensure reading success for students with ASD.

PMID- 27866350
TI  - Changes in Food Selectivity in Children with Autism Spectrum Disorder.
AB  - Food selectivity is a common problem in children with autism spectrum disorder
      (ASD) and has an adverse impact on nutrient adequacy and family mealtimes.
      Despite recent research in this area, few studies have addressed whether food
      selectivity present in children with ASD persists into adolescence. In this
      study, we assessed food selectivity in 18 children with ASD at two time points
      (mean age = 6.8 and 13.2 years), and examined changes in food selectivity. While
      food refusal improved overall, we did not observe an increase in food repertoire
      (number of unique foods eaten). These findings support the need for interventions
      early in childhood to increase variety and promote healthy eating among children
      with ASD.

PMID- 27866352
TI  - Friendship Satisfaction in Children with Autism Spectrum Disorder and Nominated
      Friends.
AB  - The current study examined the level of friendship satisfaction of children with
      autism spectrum disorder (ASD) and their nominated friends (with and without
      diagnosis of ASD). A total of 77 target children with ASD and friends from 49
      nominated friendships participated in the study. Relatively high levels of
      friendship satisfaction were reported by both target children and their nominated
      friends with no overall difference between dyads involving typically developing
      friends and friends with ASD. Analysis at the individual dyad level showed a high
      level of agreement on the reported level of satisfaction across the target
      participants and their friends. Limitations and directions for future research
      are presented.

PMID- 27866351
TI  - Social Referencing Gaze Behavior During a Videogame Task: Eye Tracking Evidence
      from Children With and Without ASD.
AB  - The purpose of this study was to understand the social referencing behaviors of
      children with and without autism spectrum disorder (ASD) while visually attending
      to a videogame stimulus depicting both the face of the videogame player and the
      videogame play action. Videogames appear to offer a uniquely well-suited
      environment for the emergence of friendships, but it is not known if children
      with and without ASD attend to and play videogames similarly. Eyetracking
      technology was used to investigate visual attention of participants matched based
      on chronological age. Parametric and nonparametric statistical analyses were used
      and results indicated the groups did not differ on percentage of time spent
      visually attending to any of the areas of interest, with one possible exception.

PMID- 27866353
TI  - Nimesulide inhibits pathogenic fungi: PGE2-dependent mechanisms.
AB  - Certain non-steroidal anti-inflammatory drugs can inhibit fungal growth, fungal
      prostaglandin E2 production, and enzyme activation. This study aims to
      investigate the antifungal effect of nimesulide against pathogenic filamentous
      fungi and yeast. The experiments detailed below were also designed to investigate
      whether the action is dependent on E2 fungal prostaglandins. Our data showed that
      nimesulide exhibited potent antifungal activity, mainly against Trichophyton
      mentagrophytes (ATCC 9533) and Cryptococcus neoformans with MIC values of 2 and
      62 MUg/mL, respectively. This drug was also able to inhibit the growth of clinic
      isolates of filamentous fungi, such as Aspergillus fumigatus, and dermatophytes,
      such as T. rubrum, T. mentagrophytes, Epidermophyton floccosum, Microsporum
      canis, and M. gypseum, with MIC values ranging from 112 to 770 MUg/mL. Our data
      also showed that the inhibition of fungal growth by nimesulide was mediated by a
      mechanism dependent on PGE2, which led to the inhibition of essential fungal
      enzymes. Thus, we concluded that nimesulide exerts a fungicidal effect against
      pathogenic filamentous fungi and yeast, involving the inhibition of fungal
      prostaglandins and fungal enzymes important to the fungal growth and
      colonization.

PMID- 27866354
TI  - Isolation and characterization of a novel glycosyl hydrolase family 74 (GH74)
      cellulase from the black goat rumen metagenomic library.
AB  - This study aimed to isolate and characterize a novel cellulolytic enzyme from
      black goat rumen by using a culture-independent approach. A metagenomic fosmid
      library was constructed from black goat rumen contents and screened for a novel
      cellulase. The KG37 gene encoding a protein of 858 amino acid residues (92.7 kDa)
      was isolated. The deduced protein contained a glycosyl hydrolase family 74 (GH74)
      domain and showed 77% sequence identity to two endo-1,4-beta-glucanases from
      Fibrobacter succinogenes. The novel GH74 cellulase gene was overexpressed in
      Escherichia coli, and its protein product was functionally characterized. The
      recombinant GH74 cellulase showed a broad substrate spectrum. The enzyme
      exhibited its optimum activity at pH 5.0 and temperature range of 20-50  degrees
      C. The enzyme was thermally stable at pH 5.0 and at a temperature of 20-40 
      degrees C. The novel GH74 cellulase can be practically exploited to convert
      lignocellulosic biomass to value-added products in various industrial
      applications in future.

PMID- 27866356
TI  - Effect of Feeding and Withdrawal of Vanadium and Vitamin C on Egg Quality and
      Vanadium Residual Over Time in Laying Hens.
AB  - This experiment examined the egg quality of hens fed vanadium (V) and vitamin C
      (VC) during storage, as well as the V and VC withdrawal on egg quality and V
      residual in egg. A total of 360 laying hens (31 weeks old) were randomly allotted
      into a 3 * 2 factorial arrangement treatments (6 replicates and 10 chicks per
      replicate) with three levels of dietary V (0, 5, and 10 mg/kg) and two levels of
      VC (0 and 100 mg/kg) for 19 weeks (feeding V and VC 12 weeks, recovery 7 weeks).
      The V residual in eggs at 4, 8, and 12th weeks were increased (linear effect, P
      <= 0.01) as V levels increased and was not detected in albumen at 7th week after
      V withdrawal. Followed by 12-week feeding period, albumen height and Haugh unit
      of eggs during 2-week storage were decreased (linear and quadratic effect, P <
      0.01) by dietary V supplementation. Lightness value was increased (linear effect,
      P < 0.01), whereas redness and yellowness value of the eggshell were lowered
      (linear effect, P < 0.01) in V-containing diet. During 7-week withdrawal period,
      eggs from groups pre-feeding 5 and 10 mg/kg V had lower (linear effect, P < 0.01)
      overall albumen height and Haugh unit. The reducing effect on albumen height and
      HU continued to be observed until the seventh week, whereas the bleaching effect
      on eggshell color disappeared after 1-week withdrawal. The results indicated that
      feeding 5 or 10 mg/kg V increases egg V residual and reduces egg albumen quality
      and bleached the shell color, and the impaired albumen quality induced by 10
      mg/kg of V lasted at least 6 weeks after changing to no V supplementation diet.
      The addition of VC did not show to affect egg quality during storage or recovery
      phase.

PMID- 27866357
TI  - An Optimal Dietary Zinc Level of Brown-Egg Laying Hens Fed a Corn-Soybean Meal
      Diet.
AB  - An experiment was conducted to estimate the optimal dietary zinc (Zn) level of
      brown-egg laying hens fed a corn-soybean meal diet from 20 to 40 weeks of age. A
      total of 120 20-week-old Beijing Red commercial laying hens were randomly
      allotted by bodyweight to one of five treatments with six replicates of four
      birds each in a completely randomized design, and fed a Zn-unsupplemented corn
      soybean meal basal diet containing 27.95 mg Zn/kg by analysis and the basal diets
      supplemented with 30, 60, 90, or 120 mg Zn/kg as Zn sulfate (reagent grade
      ZnSO4.7H2O) for a duration of 20 weeks. Laying performance, egg quality, tissue
      Zn concentrations, and activities of serum alkaline phosphatase (AKP), and liver
      copper-Zn superoxide dismutase (CuZnSOD) were measured. Regression analyses were
      performed to estimate an optimal dietary Zn level whenever a significant
      quadratic response (P < 0.05) was observed. Tibia Zn concentration (P = 0.002)
      and serum AKP activity (P = 0.010) showed significant quadratic responses to
      dietary supplemental Zn levels. The estimates of dietary Zn requirements for
      brown-egg laying hens from 20 to 40 weeks of age were 71.95 and 64.63 mg/kg for
      tibia Zn concentration and serum AKP activity, respectively. The results from
      this study indicate that the tibia Zn might be a more suitable and reliable
      parameter for Zn requirement estimation, and the optimal dietary Zn level would
      be about 72 mg/kg for brown-egg laying hens fed a corn-soybean meal diet from 20
      to 40 weeks of age.

PMID- 27866358
TI  - Anemia and Dental Caries in Pregnant Women: a Prospective Cohort Study.
AB  - The objective was to evaluate the effect of anemia during pregnancy on the risk
      of dental caries development in pregnant women. A prospective cohort including a
      sample of pregnant women in a prenatal care unit of Sao Luis, Brazil, was done.
      The incidence of dental caries during pregnancy, according to Nyvad's criteria,
      was the outcome. The main independent variables were serum iron, ferritin,
      hemoglobin, erythrocyte, hematocrit, mean corpuscular volume (MCV), mean
      corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC),
      and red cell distribution width (RDW). Pregnant women (n = 121) were evaluated at
      two moments: up to 16th week of gestational age (T1) and in the last trimester of
      pregnancy (T2). Crude and adjusted associations were estimated by the incidence
      ratio risk (IRR) and respective 95% confidence intervals (95%CI). After
      adjustment, higher serum concentrations of ferritin (IRR = 0.97, 95%CI 0.95-0.99)
      in T1, and Fe (IRR = 0.99, 95%CI 0.98-0.99), ferritin (IRR = 0.99, 95%CI 0.98
      0.99), erythrocyte (IRR = 0.71, 95%CI 0.50-0.99), hemoglobin (IRR = 0.84, 95%CI
      0.73-0.96), hematocrit (IRR = 0.93, 95%CI 0.88-0.98), MCV (IRR = 0.91, 95%CI 0.86
      0.96), and MCH (IRR = 0.83, 95%CI 0.74-0.93) in T2, were associated with fewer
      incidence of dental caries in pregnant women. Iron deficiency anemia during
      pregnancy is a risk factor for the incidence of dental caries in these women.

PMID- 27866359
TI  - Evaluation of coarse and fine particles in diverse Indian environments.
AB  - The estimates of airborne fine particle (PM2.5) concentrations are possible
      through rigorous empirical correlations based on the monitored PM10 data.
      However, such correlations change depending on the nature of sources in diverse
      ambient environments and, therefore, have to be environment specific. Studies
      presenting such correlations are limited but needed, especially for those areas,
      where PM2.5 is not routinely monitored. Moreover, there are a number of studies
      focusing on urban environments but very limited for coal mines and coastal areas.
      The aim of this study is to comprehensively analyze the concentrations of both
      PM10 and PM2.5 and develop empirical correlations between them. Data from 26
      different sites spread over three distinct environments, which are a relatively
      clean coastal area, two coal mining areas, and a highly urbanized area in Delhi
      were used for the study. Distributions of PM in the 0.43-10-MUm size range were
      measured using eight-stage cascade impactors. Regression analysis was used to
      estimate the percentage of PM2.5 in PM10 across distinct environments for source
      identification. Relatively low percentage of PM2.5 concentrations (21, 28, and
      32%) in PM10 were found in clean coastal and two mining areas, respectively.
      Percentage of PM2.5 concentrations in PM10 in the highly urbanized area of Delhi
      was 51%, indicating a presence of a much higher percentage of fine particles due
      to vehicular combustion in Delhi. The findings of this work are important in
      estimating concentrations of much harmful fine particles from coarse particles
      across distinct environments. The results are also useful in source
      identification of particulates as differences in the percentage of PM2.5
      concentrations in PM10 can be attributed to characteristics of sources in the
      diverse ambient environments.

PMID- 27866355
TI  - The descriptive epidemiology of DSM-IV Adult ADHD in the World Health
      Organization World Mental Health Surveys.
AB  - We previously reported on the cross-national epidemiology of ADHD from the first
      10 countries in the WHO World Mental Health (WMH) Surveys. The current report
      expands those previous findings to the 20 nationally or regionally representative
      WMH surveys that have now collected data on adult ADHD. The Composite
      International Diagnostic Interview (CIDI) was administered to 26,744 respondents
      in these surveys in high-, upper-middle-, and low-/lower-middle-income countries
      (68.5% mean response rate). Current DSM-IV/CIDI adult ADHD prevalence averaged
      2.8% across surveys and was higher in high (3.6%)- and upper-middle (3.0%)- than
      low-/lower-middle (1.4%)-income countries. Conditional prevalence of current ADHD
      averaged 57.0% among childhood cases and 41.1% among childhood subthreshold
      cases. Adult ADHD was significantly related to being male, previously married,
      and low education. Adult ADHD was highly comorbid with DSM-IV/CIDI anxiety, mood,
      behavior, and substance disorders and significantly associated with role
      impairments (days out of role, impaired cognition, and social interactions) when
      controlling for comorbidities. Treatment seeking was low in all countries and
      targeted largely to comorbid conditions rather than to ADHD. These results show
      that adult ADHD is prevalent, seriously impairing, and highly comorbid but vastly
      under-recognized and undertreated across countries and cultures.

PMID- 27866360
TI  - Effect of the edaphic factors and metal content in soil on the diversity of
      Trichoderma spp.
AB  - Influence of edaphic factors and metal content on diversity of Trichoderma
      species at 14 different soil sampling locations, on two depths, was examined.
      Forty-one Trichoderma isolates from 14 sampling sites were determined as nine
      species based on their internal transcribed spacer (ITS) sequences. Our results
      indicate that weakly alkaline soils are rich sources of Trichoderma strains.
      Also, higher contents of available K and P are connected with higher Trichoderma
      diversity. Increased metal content in soil was not inhibiting factor for
      Trichoderma species occurrence. Relationship between these factors was confirmed
      by locally weighted sequential smoothing (LOESS) nonparametric smoothing
      analysis. Trichoderma strain (Szeged Microbiology Collection (SZMC) 22669) from
      soil with concentrations of Cr and Ni above remediation values should be tested
      for its potential for bioremediation of these metals in polluted soils.

PMID- 27866361
TI  - Hydrogeochemical characterization of the thermal springs in northeastern of Los
      Cabos Block, Baja California Sur, Mexico.
AB  - The existence of hot springs in the northeastern part of Los Cabos Baja
      California Sur (BCS), is known from pre-Hispanic times, but their hydrochemical
      composition had not been previously described. Several springs are located within
      the watershed of Santiago, and the objective of this study was to define the
      hydrogeochemical composition of the thermal springs and to characterize the
      geothermal reservoir. A total of 16 water samples were taken in 11 geothermal
      manifestations under dry (June 2014) and humid (March 2015) conditions. A
      geothermal system of low enthalpy and low mineralization was found along the San
      Jose del Cabo Fault (FSJC), with an average salinity (TDS) of 261 mg/L and an
      alkaline pH (8.5-9.5). The hydrogeochemical composition corresponds to the sodium
      bicarbonate type, and geothermometers (silica and Na-K) indicate temperatures
      ranging from 70 to 115  degrees C for the deep thermal reservoir in conditions of
      equilibrium. The thermal springs with these hydrogeochemical characteristics
      differ in respect to the hydrochemical composition of the springs, formally
      described on several sites of BCS. Br/Cl and B/Cl ratios as well as the
      enrichment factor (EF) indicate that rainwater with a seawater component
      represents the source of the thermal spring water. In the springs, a mixture
      between thermal water and surface water is observed, combined with a relatively
      deep water circulation, allowing a calcium-sodium exchange, according to the host
      rock geochemistry. The higher temperatures found at some hot springs are related
      to the main trace of the San Jose del Cabo Fault.

PMID- 27866362
TI  - Proteomic response of oat leaves to long-term salinity stress.
AB  - Salinity adversely affects plant growth and production. Oat is a moderately salt
      tolerant crop and can contribute to improving saline soil. The physiological and
      molecular responses of the oat plant to long-term salinity were studied. After a
      16-day salt treatment (150 mmol L-1NaCl in Hoagland's solution), photosynthetic
      rate, maximum photosystem II photochemical efficiency, and actual efficiency of
      photosystem II decreased. The activities of superoxide dismutase, peroxidase, and
      catalase significantly increased. We also investigated the protein profiles of
      oat leaves in response to salinity and detected 30 reproducible protein spots by
      two-dimensional gel electrophoresis that were differentially abundant.
      Specifically, one protein was up-regulated and 29 proteins were down-regulated
      compared with the control. These 29 proteins were identified using MALDI-TOF mass
      spectrometry, and 19 corresponding genes were further investigated by
      quantitative real-time PCR. These proteins were involved in four types of
      biological processes: photosynthesis, carbohydrate metabolism and energy, protein
      biosynthesis, and folding and detoxification. This study indicates that the lower
      levels of Calvin cycle-related proteins, 50S ribosomal protein L10 and adenosine
      triphosphate regulation-related proteins, and the high levels of antioxidant
      enzymes play important roles in the response of oat to long-term salinity stress.

PMID- 27866364
TI  - Integrative health risk assessment of air pollution in the northwest of Spain.
AB  - Levels, origins and potential risks due to different air pollutants (ozone, SO2
      and particle-borne metals) in NW Spain were investigated in eight locations
      affected by different emission sources. All monitored locations suffered the
      influence of traffic and industrial emissions, being this influence more
      important in urban locations. Although average values of the estimated hazard
      index (HI) due to particle-borne metals showed values lower than one, maximum
      values of this parameter exceeded this safety limit in urban locations. In
      general, Ni and As were identified as those metals most contributing to the HI.
      Furthermore, the presence of industrial emission episodes produced a significant
      increase in the magnitude of the HI in two of the seven urban areas. Therefore,
      the frequency and intensity of these episodes should be further investigated.
      Finally, levels of airborne and particle-borne pollutants were integrated with
      the aim of providing a comprehensive assessment of health risk. According to an
      established indexing system, air quality can be classified from good to moderate,
      being the southern urban locations (the most densely populated and industrialised
      ones) presenting the worst values. However, either the high or the low influence
      of acute and chronic-effect pollutants on air quality depends on the location.

PMID- 27866363
TI  - Comparative of Quercus spp. and Salix spp. for phytoremediation of Pb/Zn mine
      tailings.
AB  - A pot experiment was conducted to evaluate the feasibility of using tree
      seedlings for the phytoremediation of lead/zinc (Pb/Zn) mine tailings. Seedlings
      of three Quercus spp. (Q. shumardii, Q. phellos, and Q. virginiana) and rooted
      cuttings of two Salix spp. (S. matsudana and S. integra) were transplanted into
      pots containing 50 and 100 % Pb/Zn mine tailings to evaluate their tolerance of
      heavy metals. The five species showed different tolerance levels to the Pb/Zn
      tailings treatments. Q. virginiana was highly tolerant to heavy metals and grew
      normally in the Pb/Zn tailings. The root systems showed marked differences
      between the Quercus spp. and Salix spp., indicating that different mechanisms
      operated to confer tolerance of heavy metals. The maximum efficiency of
      photosystem II photochemistry value of the five species showed no differences
      among the treatments, except for Q. shumardii. All species showed low metal
      translocation factors (TFs). However, S. integra had significantly higher TF
      values for Zn (1.42-2.18) and cadmium (1.03-1.45) than did the other species. In
      this respect, Q. virginiana showed the highest tolerance and a low TF, implying
      that it is a candidate for phytostabilization of mine tailings in southern China.
      S. integra may be useful for phytoextraction of tailings in temperate regions.

PMID- 27866366
TI  - A qualitative study of patients' perceptions of the value of molecular diagnosis
      for familial hypercholesterolemia (FH).
AB  - For many years, familial hypercholesterolemia (FH), an inherited disorder, has
      been diagnosed using phenotypic features plus family history of early onset
      cardiovascular disease (CVD), and has been successfully treated using statin
      therapy. DNA testing is now available and this has been incorporated into
      familial cascade screening programmes in many parts of Europe. Little is known
      about patients' perceptions of the value of undergoing molecular diagnosis for
      FH. In-depth interviews were carried out with patients (n = 38) being treated for
      FH who were the first in their family to undergo DNA testing for FH. Data were
      analysed thematically. While interviewees regarded DNA testing as an
      unexceptional event, it was seen as a positive innovation because it confirmed
      that their family carried a particular disorder, offered an aetiological
      explanation for their hypercholesterolemia and provided information about their
      own and family members' future risks. From the patient perspective, the main
      benefit of molecular diagnosis lies in its ability to provide information which
      allows (younger) family members to access genetic screening and, thus, timely
      treatment. The implications for future developments in genetic services and the
      need to investigate further the provision of molecular testing in mainstream
      specialties are briefly discussed.

PMID- 27866365
TI  - Periodontal status in crack and cocaine addicted men: a cross-sectional study.
AB  - This cross-sectional study evaluated the association between crack/cocaine
      addiction and periodontal disease in men. Periodontal examination (probing depth,
      clinical attachment level, bleeding on probing, and plaque index) and interviews
      were performed in 160 patients (>=18 years) from the Federal University of Bahia.
      Crack and cocaine dependence was defined according to the medical records and
      interviews of each patient; all drug addicted volunteers used both crack and
      cocaine. T test, Chi-square test, and logistic regression were used to assess the
      associations between destructive periodontal disease and crack/cocaine dependence
      (p <= 0.05). Probing depth was significantly greater in crack/cocaine addicted
      individuals (2.84 +/- 0.76 mm) compared with non-addicted individuals (2.55 +/-
      0.73 mm, p = 0.04). After adjusting for covariates, periodontitis was not
      significantly associated with crack/cocaine addiction (OR = 2.31, 95 % CI = 0.82
      6.46, p = 0.11), which was only associated with age >=35 years (OR = 4.16, 95 %
      CI = 1.65-10.50, p = 0.003) and higher dental plaque index (OR = 6.46, 95 % CI =
      1.95-21.42, p = 0.002). In conclusion, although probing depth was greater in
      crack/cocaine addicted individuals, destructive periodontal disease was not
      associated with crack and cocaine addiction in the present population.
      Destructive periodontal disease was associated with age and dental plaque.
      Further studies in a larger sample size are required to confirm the results.

PMID- 27866367
TI  - Risk for latent and active tuberculosis in Germany.
AB  - PURPOSE: Few individuals that are latently infected with M. tuberculosis latent
      tuberculosis infection(LTBI) progress to active disease. We investigated risk
      factors for LTBI and active pulmonary tuberculosis (PTB) in Germany. METHODS:
      Healthy household contacts (HHCs), health care workers (HCWs) exposed to M.
      tuberculosis and PTB patients were recruited at 18 German centres. Interferon
      gamma release assay (IGRA) testing was performed. LTBI risk factors were
      evaluated by comparing IGRA-positive with IGRA-negative contacts. Risk factors
      for tuberculosis were evaluated by comparing PTB patients with HHCs. RESULTS:
      From 2008-2014, 603 HHCs, 295 HCWs and 856 PTBs were recruited. LTBI was found in
      34.5% of HHCs and in 38.9% of HCWs. In HCWs, care for coughing patients (p =
      0.02) and longstanding nursing occupation (p = 0.04) were associated with LTBI.
      In HHCs, predictors for LTBI were a diseased partner (odds ratio 4.39), sexual
      contact to a diseased partner and substance dependency (all p < 0.001). PTB was
      associated with male sex, low body weight (p < 0.0001), alcoholism (15.0 vs 5.9%;
      p < 0.0001), glucocorticoid therapy (7.2 vs 2.0%; p = 0.004) and diabetes (7.8
      vs. 4.0%; p = 0.04). No contact developed active tuberculosis within 2 years
      follow-up. CONCLUSIONS: Positive IGRA responses are frequent among exposed HHCs
      and HCWs in Germany and are poor predictors for the development of active
      tuberculosis.

PMID- 27866368
TI  - Does serum procalcitonin aid in the diagnosis of bloodstream infection regardless
      of whether patients exhibit the systemic inflammatory response syndrome?
AB  - BACKGROUND: Physicians frequently rely on the systemic inflammatory response
      syndrome (SIRS) criteria to detect bloodstream infections (BSIs). We evaluated
      the diagnostic performance of procalcitonin (PCT) in detecting BSI in patients
      with and without SIRS. METHODS: We tested the association between BSI, serum PCT
      levels, contemporaneous SIRS scores and serum lactate using logistic regression
      in a dataset of 4279 patients. The diagnostic performance of these variables was
      assessed. RESULTS: In multivariate regression analysis, only log(PCT) was
      independently associated with BSI (p < 0.05). The mean area under the curve (AUC)
      of PCT in detecting BSI (0.683; 95% CI 0.65-0.71) was significantly higher than
      serum lactate (0.615; 95% CI 0.58-0.64) and the SIRS score (0.562; 95% CI 0.53
      0.58). The AUC of PCT did not differ significantly by SIRS status. PCT of less
      than 0.1 ng/mL had a negative predictive value (NPV) of 97.4 and NPV of 96.2% for
      BSI in the SIRS-negative and SIRS-positive patients, respectively. A PCT of
      greater than 10 ng/mL had a LR of 6.22 for BSI in SIRS-negative patients. The
      probability of BSI increased exponentially with rising PCT levels regardless of
      SIRS status. CONCLUSION: The performance of PCT for the diagnosis of BSI was not
      affected by SIRS status. Only PCT was independently associated with BSI, while
      the SIRS criterion and serum lactate were not. A low PCT value may be used to
      identify patients at a low risk for having BSI in both settings. An elevated PCT
      value even in a SIRS negative patient should prompt a careful search for BSI.

PMID- 27866369
TI  - Fate of deoxynivalenol and deoxynivalenol-3-glucoside during cereal-based thermal
      food processing: a review study.
AB  - Deoxynivalenol (DON), the most commonly occurring trichothecene in nature, may
      affect animal and human health through causing diarrhea, vomiting,
      gastrointestinal inflammation, and immunomodulation. DON-3-glucoside (DON-3G) as
      a major plant metabolite of the mycotoxin is another "emerging" food safety issue
      in recent years. Humans may experience potential health risks by consuming DON
      contaminated food products. Thus, it is crucial for human and animal health to
      study also the degradation of DON and DON-3G during thermal food processing.
      Baking, boiling, steaming, frying, and extrusion cooking are commonly used during
      thermal food processing and have promising effects on the reduction of mycotoxins
      in food. For DON, however, the observed effects of these methods, as reported in
      numerous studies, are ambiguous and do not present a clear picture with regard to
      reduction or transformation. This review summarized the influence of thermal
      processing on the stability of DON and the formation of degradation/conversion
      products. Besides this, also a release of DON and DON-3G from food matrix as well
      as the release of DON from DON-3G during processing is discussed. In addition,
      some conflicting findings as reported from the studies on thermal processing as
      well as cause-effect relationships of the different thermal procedures are
      explored. Finally, the potential toxic profiles of DON degradation products are
      discussed as well when data are available.

PMID- 27866371
TI  - Sparse multidimensional iterative lineshape-enhanced (SMILE) reconstruction of
      both non-uniformly sampled and conventional NMR data.
AB  - Implementation of a new algorithm, SMILE, is described for reconstruction of non
      uniformly sampled two-, three- and four-dimensional NMR data, which takes
      advantage of the known phases of the NMR spectrum and the exponential decay of
      underlying time domain signals. The method is very robust with respect to the
      chosen sampling protocol and, in its default mode, also extends the truncated
      time domain signals by a modest amount of non-sampled zeros. SMILE can likewise
      be used to extend conventional uniformly sampled data, as an effective
      multidimensional alternative to linear prediction. The program is provided as a
      plug-in to the widely used NMRPipe software suite, and can be used with default
      parameters for mainstream application, or with user control over the iterative
      process to possibly further improve reconstruction quality and to lower the
      demand on computational resources. For large data sets, the method is robust and
      demonstrated for sparsities down to ca 1%, and final all-real spectral sizes as
      large as 300 Gb. Comparison between fully sampled, conventionally processed
      spectra and randomly selected NUS subsets of this data shows that the
      reconstruction quality approaches the theoretical limit in terms of peak position
      fidelity and intensity. SMILE essentially removes the noise-like appearance
      associated with the point-spread function of signals that are a default of five
      fold above the noise level, but impacts the actual thermal noise in the NMR
      spectra only minimally. Therefore, the appearance and interpretation of SMILE
      reconstructed spectra is very similar to that of fully sampled spectra generated
      by Fourier transformation.

PMID- 27866370
TI  - Perspective: revisiting the field dependence of TROSY sensitivity.
AB  - The discovery of the TROSY effect (Pervushin et al. in Proc Natl Acad Sci USA
      94:12366-12371, 1997) for reducing transverse relaxation and line sharpening
      through selecting pathways in which dipole-dipole and CSA Hamiltonians partially
      cancel each other had a tremendous impact on solution NMR studies of
      macromolecules. Together with the methyl TROSY (Tugarinov and Kay in J Biomol NMR
      28:165-172, 2004) it enabled structural and functional studies of significantly
      larger systems. The optimal field strengths for TROSY have been estimated to be
      on spectrometers operating around 900 MHz (21.14 T) for the 1HN TROSY (Pervushin
      et al. in Proc Natl Acad Sci USA 94:12366-12371, 1997) while the aromatic 13C
      (13Caro) TROSY is posited to be optimal at around 600 MHz (14.09 T) (Pervushin et
      al. in J Am Chem Soc 120:6394-6400, 1998b; Pervushin in Q Rev Biophys 33:161-197,
      2000). The initial rational was based on the consideration of where the quadratic
      B0 field dependences of the TROSY relaxation rates reach a minimum. For
      sensitivity consideration, however, it is interesting to estimate which field
      strengths yield the tallest peaks. Recent studies of 15N-detected TROSYs
      suggested that maximal peak heights are expected at 1.15 GHz (27.01 T) although
      the slowest relaxation rates or longest transverse relaxation times T2 are indeed
      expected around 900 MHz (21.14 T) (Takeuchi in J Biomol NMR 63:323-331, 2015;
      Takeuchi et al. in J Biomol NMR 64:143-151, 2016). This was based on the fact
      that the heights of Lorentzian lines are proportional to B o3/2 * T2 (Bo). Thus,
      multiplying the parabolic T2(Bo) dependence with the increasing function of B
      o3/2 shifts the maxima of peak-height field dependence from the T2 maximum at 900
      MHz to higher fields. Moreover, besides shifting the peak height maximum for 15N
      TROSY, this analysis yields estimates for optimal peak heights for 1HN detected
      TROSY to 1.5 GHz, and to 900 MHz for 13C-detected 13CaroTROSY as is detailed
      below. To our knowledge, this aspect of field dependence of TROSY sensitivity has
      not been in the attention of the NMR community but may affect perspectives of NMR
      at ultra-high fields.

PMID- 27866372
TI  - Input, behaviour and distribution of multiple elements in abiotic matrices along
      a transect within the Okavango Delta, northern Botswana.
AB  - Wetlands fed by rivers can be a sink for elements depending on elemental
      concentrations, wetland hydrology, geochemistry, vegetation and climate. In the
      case of the Okavango Delta, northern Botswana, the outflow discharge is a small
      fraction (2-5%) of the inflow. This has strong potential consequences for the
      Delta, as it strongly affects element cycling and storage within the Delta. We
      estimated the inputs, behaviour and distribution of multiple elements along a
      longitudinal transect within the Okavango Delta, to show potential effects of
      retention mechanisms of different elements. High annual element input is rather
      attributed to discharge than to the concentration within the water, which is
      generally extremely low. We observed minimal enrichment of the elements within
      the water pathway along the transect from inflow to outlets, implying that
      element output is negligible. For most elements, we observed a high correlation
      between storage and sediment organic matter content. The organic matter content
      within the sediments was higher in the vegetated sediments than in non-vegetated
      sediments (factor ~ 10), and a similar trend was found for most elements. In
      conclusion, organic matter dominated in sediments from vegetated plots and thus
      plays an important role in retaining the elements within the sediments of the
      Delta. This finding has major implications for e.g. planning constructed wetlands
      for water purification or element retention especially in areas with high
      evapotranspiration.

PMID- 27866374
TI  - Older men's experiences of accessing general practitioner services in rural
      areas.

PMID- 27866375
TI  - Pre-operative Assessment for Arteriovenous Fistula Placement for Dialysis.
AB  - Native AV fistulas are considered to be the best VA for most dialysis patients. A
      careful preoperative process of care is essential to maximize the proportion of
      fistulas that achieve adequacy for dialysis. An individualized and timely
      evaluation of patients starts early with the identification of risk factors,
      followed by a physical examination which should be complemented by ultrasound
      vascular mapping in most cases. Vascular mapping includes any technique that
      leads to information on patient's inflow and outflow anatomy (+/- hemodynamics)
      as they relate to arteriovenous access creation and may predict maturation. There
      is increasing evidence favoring the utilization of preoperative Doppler
      ultrasound which is recommended in all patients by NFK-KDOQI Guidelines. It
      allows noninvasive evaluation of both structural and functional aspects of
      vessels that play an important role in access maturation. Its major limitation is
      the relative inability to assess central vein patency. Although conventional
      venography is still the gold standard to evaluate central veins, it provides
      otherwise limited information and can incur serious adverse effects related to
      its invasive nature and contrast use. Alternatives to these two imaging
      techniques are rarely used, especially because of their higher costs and low
      availability.

PMID- 27866373
TI  - Involvement of GSK-3beta Phosphorylation Through PI3-K/Akt in Cerebral Ischemia
      Induced Neurogenesis in Rats.
AB  - Glycogen synthase kinase (GSK)-3beta, which is abundantly expressed in the
      central nervous system, regulates various cellular processes including gene
      expression, cell proliferation, and differentiation. However, involvement of GSK
      3beta in cerebral ischemia-induced endogenous neurogenesis is not yet fully
      understood. Appropriate strategies to prevent ischemic cell damage and subsequent
      severe sequelae are needed. The purpose of the present study was to determine the
      relationship between pathophysiological alteration of the GSK-3beta signaling
      pathway and cerebral ischemia-induced endogenous neurogenesis in rats. Severe
      cerebral ischemia was produced by the injection of 700 microspheres into the
      right internal carotid artery of rats. We demonstrated that phosphorylation of
      GSK-3beta at its Ser9 and that of Akt was significantly enhanced on day 7 after
      the cerebral ischemia, as was the number of NeuroD-positive cells. Treatment with
      a phosphatidylinositol 3-kinase (PI3-K) inhibitor decreased the cerebral ischemia
      induced phosphorylation of Akt and that of GSK-3beta at its Ser9. In addition, as
      the protein levels of insulin-like growth factor-1 (IGF-1) and brain-derived
      neurotrophic factor (BDNF) were decreased, they might not have been essential for
      activation of the PI3-K/Akt/GSK-3beta pathway after severe cerebral ischemia.
      Although it remains to be determined what factors activate this pathway, our
      results suggest that PI3K/Akt-dependent GSK-3beta signaling and subsequent
      expression of NeuroD were involved in the neurogenesis elicited by cerebral
      ischemia.

PMID- 27866376
TI  - Reduction in Dietary Acrylamide Exposure-Impact of Potatoes with Low Acrylamide
      Potential.
AB  - Acrylamide forms primarily from a reaction between reducing sugars (e.g., glucose
      and fructose) and an amino acid (asparagine, Asn) formed naturally in foods,
      including potatoes. This reaction occurs when carbohydrate-rich foods are heated
      at temperatures above 120  degrees C. Multiple potato varieties were transformed
      with potato genomic DNA that results in down-regulation of the expression of the
      asparagine synthetase-1 gene (Asn1), significantly reducing synthesis of free
      Asn, and consequently lowering the potential to form acrylamide during cooking.
      These potatoes with low acrylamide potential (LAP) were tested in agronomic
      trials, and processed into French fries and potato chips. Decreased levels of
      acrylamide were measured in these cooked food products when derived from LAP
      potatoes compared with those derived from conventional potatoes. These reductions
      can be directly attributed to reduction in Asn levels in the LAP potatoes. The
      corresponding average reduction in exposure to acrylamide from French fry and
      potato chip consumption is estimated to be 65%, which would amount to
      approximately a 25% reduction in overall dietary exposure. Considering that
      children consume nearly three times more acrylamide than adults on a per kg body
      weight basis, they would experience the most impact from the reduced acrylamide
      associated with LAP potatoes. The potential public health impacts, in context of
      dietary acrylamide exposure reduction, are discussed in this study.

PMID- 27866378
TI  - Four-month-old infants individuate and track simple tools following functional
      demonstrations.
AB  - Two experiments examined whether 4-month-olds (n = 120) who were induced to
      assign two objects to different categories would then be able to take advantage
      of these contrastive categorical encodings to individuate and track the objects.
      In each experiment, infants first watched functional demonstrations of two tools,
      a masher and tongs (Experiment 1) or a marker and a knife (Experiment 2). Next,
      half the infants saw the two tools brought out alternately from behind a screen,
      which was then lowered to reveal only one of the tools (different-objects
      condition); the other infants saw similar events except that the same tool was
      shown on either side of the screen (same-object condition). In both experiments,
      infants in the different-objects condition looked reliably longer than those in
      the same-object condition, and this effect was eliminated if the demonstrations
      involved similar but non-functional actions. Together, these results indicate
      that infants (a) were led by the functional demonstrations they observed to
      assign the two tools to distinct categories, (b) recruited these categorical
      encodings to individuate and track the tools, and hence (c) detected a violation
      in the different-objects condition when the screen was lowered to reveal only one
      tool. Categorical information thus plays a privileged role in individuation and
      identity tracking from a very young age.

PMID- 27866377
TI  - Unusual cause of hypercalcaemia in end stage renal failure patients.
AB  - Immobility-induced hypercalcaemia is rarely considered in patients on dialysis
      and is a challenging diagnosis to make. This is especially so due to the lack of
      biomarkers as well as the notion that calcium metabolism is mostly related to
      chronic kidney disease-metabolic bone disorder due to the role of iPTH. We
      present two cases of our dialysis patients, who were clinically unwell from
      hypercalcemia. We were initially uncertain of the cause of hypercalcemia as
      despite our attempts to adjust treatment based on their biochemical findings, we
      were unable to correct the hypercalcemia. We did not have appropriate bone
      turnover markers to guide us and out of desperation, anti-resorptives-calcitonin
      and bisphosphonate were given with good clinical response. We concluded that the
      hypercalcemia was related to immobility-induced hypercalcemia and the
      inappropriately low iPTH was a red herring. Immobility-induced hypercalcaemia
      should be considered in patients with end stage renal failure on renal
      replacement therapy, especially in those with recent and significant immobility.
      In these patients, pamidronate can be considered should the hypercalcaemia
      persist.

PMID- 27866380
TI  - IMAGING DIAGNOSIS-ULTRASOUND UNCOMMON FEATURES OF AN ABDOMINAL GOSSYPIBOMA IN A
      DOG.
AB  - An abdominal mass was incidentally detected in a 12-year-old, neutered female,
      crossed breed dog. Abdominal ultrasonographic examination showed a well
      delineated, irregular, heterogeneous mass that did not generate any distal
      acoustic shadowing. Transcutaneous US-guided biopsy of the mass were
      nonconclusive but raised the possibility of neoplasia. Surgery discovered a mass
      embedded in the omentum and a large quantity of surgical sponges were identified
      in cut section. To the authors' knowledge, this represents the first published
      case of gossypiboma casting no characteristic distal acoustic shadowing.

PMID- 27866381
TI  - CARDIAC MAGNETIC RESONANCE IMAGING OF PATENT DUCTUS ARTERIOSUS IN THREE DOGS.
AB  - Patent ductus arteriosus (PDA) is the most common congenital cardiovascular
      disorder in dogs and requires an accurate diagnosis for an appropriate treatment.
      Cardiac MRI (cMRI) has been reported as a method for characterization of canine
      thoracic vasculature. However, to the authors' knowledge, no published studies
      describe evaluation of canine PDA through cMRI. Three dogs were selected for this
      exploratory study. Electrocardiogram gating and breath-hold techniques were
      performed using a 3T MR scanner. Both black blood imaging and bright blood cine
      acquisitions were performed. Quantification of stroke volume (SV) and shunting
      volume were calculated using a stack of short-axis cine images. Additional 4D
      (three-spatial dimensions plus time)-TRAK (time-resolved MR angiography with
      keyhole) sequences were conducted in patient 2 to verify other vasculature
      abnormality. Black blood images clearly depicted the course of the ductus from
      the descending aorta to the pulmonary artery in all three dogs. Morphological
      evaluation of PDA classified patients 1 and 2 as Type 2a and patient 3 as Type 1.
      Patient 2 was confirmed to have a concurrent persistent left cranial vena cava.
      Left ventricular SV, right ventricular SV, and left-to-right SV ratio were 12.4
      ml, 3.36 ml, and 3.704, respectively, in patient 1; 6.85 ml, 1.22 ml, and 5.60 in
      the patient 2; and 3.67 ml, 2.14 ml, and 1.702 in patient 3. Findings indicated
      that cMRI is a feasible method for characterizing the morphology of PDA and
      extracardiac vasculature anomalies in dogs.

PMID- 27866379
TI  - Effects of oral exposure to the phthalate substitute acetyl tributyl citrate on
      female reproduction in mice.
AB  - Acetyl tributyl citrate (ATBC), is a phthalate substitute used in food and
      medical plastics, cosmetics and toys. Although systemically safe up to 1000 mg kg
      1  day-1 , its ability to cause reproductive toxicity in females at levels below
      50 mg kg-1  day-1 has not been examined. This study evaluated the effects of
      lower ATBC exposures on female reproduction using mice. Adult CD-1 females (n = 7
      8 per treatment) were dosed orally with tocopherol-stripped corn oil (vehicle), 5
      or 10 mg kg-1  day-1 ATBC daily for 15 days, and then bred with a proven breeder
      male. ATBC exposure did not alter body weights, estrous cyclicity, and
      gestational and litter parameters. Relative spleen weight was slightly increased
      in the 5 mg kg-1  day-1 group. ATBC at 10 mg kg-1  day-1 targeted ovarian
      follicles and decreased the number of primordial, primary and secondary follicles
      present in the ovary. These findings suggest that low levels of ATBC may be
      detrimental to ovarian function, thus, more information is needed to understand
      better the impact of ATBC on female reproduction. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27866382
TI  - Immunotoxic effects of in vitro exposure of dolphin lymphocytes to Louisiana
      sweet crude oil and CorexitTM.
AB  - The Deepwater Horizon oil spill was one of the worst environmental disasters on
      record in the United States. Response efforts to reduce the magnitude of the oil
      slick included the use of thousands of gallons of the chemical dispersant
      CorexitTM in surface and deep-water environments. The immunotoxicity of Louisiana
      sweet crude oil and the chemical dispersant Corexit was examined using lymphocyte
      proliferation (LP) and natural killer cell (NK) assays as measures of impact on
      the adaptive (LP) and innate (NK) immune response in bottlenose dolphins. Study
      results show that both high-energy media-accommodated fractions (MAF) and
      chemically enhanced MAF (CEMAF) mixtures modulate immune function. Following
      exposure to Louisiana sweet crude, both B- and T-cell proliferation of white
      blood cells was increased for all exposure concentrations, compared to control;
      however, this increase was only significant for the 50% and 100% treatments. In
      contrast, exposure of white blood cells to the CEMAF mixture significantly
      decreased both T- and B-cell proliferation in the 25%, 50% and 100% treatments.
      NK cell activity was enhanced significantly by CEMAF mixtures for the 50% and
      100% treatments. The immunosuppression of LP at environmentally relevant
      concentrations of oil and dispersant suggests that marine mammals may be unable
      to mount an adequate defense against xenobiotic threats following exposure to oil
      and dispersant, leaving them more susceptible to disease. In contrast, NK cell
      activity was significantly enhanced, which may increase an organism's tumor or
      viral surveillance ability by mounting an enhanced immune response. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27866383
TI  - Perceptions of Peer Sexual Behavior: Do Adolescents Believe in a Sexual Double
      Standard?
AB  - BACKGROUND: The purpose of the study was to (1) examine attitudes of adolescents
      toward peer models having sex or choosing abstinence, and (2) determine whether a
      "double standard" in perception existed concerning adolescent abstinence and
      sexual behavior. METHODS: Adolescents (N = 173) completed questionnaires that
      included 1 of 6 randomly assigned vignettes that described male and female peer
      models 3 ways: (1) no information about model's sexual behavior, (2) model in
      love but choosing abstinence, and (3) model in love and having sex. Participants
      read the vignette to which they had been assigned and responded to statements
      about the peer model. Data were analyzed using multivariate analysis of variance.
      RESULTS: Results did not show evidence of a sexual double standard among male
      participants, but did show some evidence of a sexual double standard among female
      participants. Additionally, both male and female participants evaluated more
      harshly peer models that were having sex than peer models that chose abstinence.
      CONCLUSIONS: Findings provide insight concerning the lack of a sexual double
      standard among male participants, the existence, to some degree, of a sexual
      double standard among female participants, and demonstrate the existence of a
      social cost to both young men and young women for choosing to have sex.

PMID- 27866384
TI  - Schoolyard Characteristics, Physical Activity, and Sedentary Behavior: Combining
      GPS and Accelerometry.
AB  - BACKGROUND: Physical activity (PA) is decreasing among children, while sedentary
      behavior (SB) is increasing. Schoolyards seem suitable settings to influence
      children's PA behavior. This study investigated the associations between
      schoolyard characteristics and moderate-to-vigorous physical activity (MVPA) and
      SB of children aged 8-11 years at schoolyards. METHODS: Twenty primary schools in
      the Netherlands were involved. A total of 257 children wore an accelerometer and
      global positioning system (GPS) device for 5 consecutive days to objectively
      assess their PA levels and presence at the schoolyard, respectively.
      Accelerometer and GPS data were merged using the personal activity and location
      measurement system. Multilevel linear regression analyses were used to study
      correlates of MVPA and SB at schoolyards. RESULTS: On average, children spent 54
      minutes a day at the schoolyard, 9 minutes of which were spent in MVPA and 20
      minutes in SB. Boys engaged in MVPA longer than girls at the schoolyard. Fixed
      equipment, such as high bars and soccer goals, teacher-initiated activities, and
      the presence of a ball games policy were correlates of more MVPA and less SB.
      CONCLUSION: Well-designed schoolyards, including PA-enhancing fixed equipment, a
      supportive PA climate created by teachers, and supportive schoolyard policies may
      contribute to increased PA and decreased SB during school recess among school
      aged children.

PMID- 27866386
TI  - Hand Hygiene Program Decreases School Absenteeism Due to Upper Respiratory
      Infections.
AB  - BACKGROUND: We assessed the effectiveness of a handwashing program using hand
      sanitizer to prevent school absenteeism due to upper respiratory infections
      (URIs). METHODS: This was a randomized, controlled, and open study on a sample of
      1341 children 4-12 years old, attending 5 state schools in Almeria (Spain), with
      an 8-month follow-up. The experimental group (EG) washed their hands with soap
      and water, together with using hand sanitizer, and the control group followed
      their usual handwashing procedures. Absenteeism rates due to URIs were compared
      between the 2 groups through a multivariate Poisson regression analysis. The
      percent of days missed in both groups were compared with a z test. RESULTS:
      Overall, 1271 cases of school absenteeism due to URIs were registered.
      Schoolchildren from the EG had a 38% lower risk of absenteeism due to URIs,
      incidence rate ratio: 0.62, 95% confidence interval: 0.55-0.70, and a decrease in
      absenteeism of 0.45 episodes/child/academic year, p < .001. Pupils missed 2734
      school days due to URIs and the percentage of days absent was significantly lower
      in the EG, p < .001. CONCLUSIONS: Use of hand sanitizer plus handwashing with
      soap accompanied by educational support is an effective measure to reduce
      absenteeism due to URIs.

PMID- 27866387
TI  - School Context Matters: The Impacts of Concentrated Poverty and Racial
      Segregation on Childhood Obesity.
AB  - BACKGROUND: Schools are important sites for interventions to prevent childhood
      obesity. This study examines how variables measuring the socioeconomic and racial
      composition of schools and counties affect the likelihood of obesity among third
      to fifth grade children. METHODS: Body mass index data were collected from third
      to fifth grade public school students by teachers from 317 urban and rural North
      Carolina schools in 38 counties. Multilevel models are used to examine county-,
      school-, and individual-level effects. RESULTS: Low concentrations of poverty at
      the school level are associated with lower odds of obesity. Schools in rural
      counties had significantly higher rates of obesity, net the other variables in
      the model. Students in minority-segregated schools had higher rates of obesity
      than those in more racially diverse schools, but the effect was not statistically
      significant once school-level poverty was controlled. CONCLUSIONS: Place-based
      inequalities are important determinants of health inequalities. The results of
      this study show that school-level variables related to poverty are important for
      understanding and confronting childhood obesity.

PMID- 27866385
TI  - Effectiveness of Universal School-Based Mental Health Awareness Programs Among
      Youth in the United States: A Systematic Review.
AB  - BACKGROUND: Stigmatizing attitudes toward mental illness and low mental health
      literacy have been identified as links to social adversity, and barriers to
      seeking and adhering to treatment among adolescents suffering from mental
      illness. Prior research has found that it is possible to improve these outcomes
      using school-based mental health awareness interventions. The purpose of this
      study was to review empirical literature pertaining to universal mental health
      awareness interventions aiming to improve mental health related outcomes among
      students enrolled in US K-12 schools, especially minorities vulnerable to health
      disparities. METHODS: PsycINFO, Cochrane Library, PUBMED, and reference lists of
      relevant articles were searched for K-12 school-based mental health awareness
      interventions in the United States. Universal studies that measured knowledge,
      attitudes, and/or help-seeking pertinent to mental health were included. RESULTS:
      A total of 15 studies were selected to be part of the review. There were 7
      pretest/post-test case series, 5 nonrandomized experimental trial, 1 Solomon 4
      groups, and 2 randomized controlled trial (RCT) designs. Nine studies measuring
      knowledge, 8 studies measuring attitudes, and 4 studies measuring help-seeking,
      indicated statistically significant improvements. CONCLUSIONS: Although results
      of all studies indicated some level of improvement, more research on
      implementation of universal school-based mental health awareness programs is
      needed using RCT study designs, and long-term follow-up implementation.

PMID- 27866388
TI  - Increasing Prevalence of US Elementary School Gardens, but Disparities Reduce
      Opportunities for Disadvantaged Students.
AB  - BACKGROUND: We examined the prevalence of school garden programs at US public
      elementary schools. The study examined time trends, demographic and regional
      disparities, and associations with related programs such as farm-to-school.
      METHODS: Annual surveys were gathered from nationally representative samples of
      elementary schools between 2006-2007 and 2013-2014. Annual samples ranged from
      553 to 748 schools. RESULTS: The prevalence of gardens increased steadily from
      11.9% in 2006-2007 to 31.2% in 2013-2014 (p < .001). In multivariate logistic
      regressions the prevalence of garden programs varied significantly by school
      characteristics. Gardens were more prevalent in the west than in other regions.
      Gardens were less prevalent at schools serving higher proportions of lower-income
      students, and were more prevalent at urban schools than in suburbs, towns, or
      rural areas. Gardens were more common at schools with farm-to-school programs.
      Gardens also were associated with offering formal classroom-based nutrition
      education. CONCLUSIONS: Garden programs in elementary schools have increased over
      time, but there is room for wider implementation, particularly at schools serving
      lower-income students. Given the role of childhood in establishing food
      preferences and dietary consumption habits, such programs are important and can
      reinforce the messages imparted through nutrition education.

PMID- 27866389
TI  - Do Substance Use, Psychosocial Adjustment, and Sexual Experiences Vary for Dating
      Violence Victims Based on Type of Violent Relationships?
AB  - BACKGROUND: We examined whether substance use, psychosocial adjustment, and
      sexual experiences vary for teen dating violence victims by the type of violence
      in their relationships. We compared dating youth who reported no victimization in
      their relationships to those who reported being victims of intimate terrorism
      (dating violence involving one physically violent and controlling perpetrator)
      and those who reported experiencing situational couple violence (physical dating
      violence absent the dynamics of power and control). METHODS: This was a cross
      sectional survey of 3745 dating youth from 10 middle and high schools in the
      northeastern United States, one third of whom reported physical dating violence.
      RESULTS: In general, teens experiencing no dating violence reported less frequent
      substance use, higher psychosocial adjustment, and less sexual activity than
      victims of either intimate terrorism or situational couple violence. In addition,
      victims of intimate terrorism reported higher levels of depression, anxiety, and
      anger/hostility compared to situational couple violence victims; they also were
      more likely to report having sex, and earlier sexual initiation. CONCLUSIONS:
      Youth who experienced physical violence in their dating relationships, coupled
      with controlling behaviors from their partner/perpetrator, reported the most
      psychosocial adjustment issues and the earliest sexual activity.

PMID- 27866390
TI  - School-Based HIV/STD Testing Behaviors and Motivations Among Black and Hispanic
      Teen MSM: Results From a Formative Evaluation.
AB  - BACKGROUND: This evaluation explores experiences with, and motivations for, human
      immunodeficiency virus (HIV) and sexually transmitted disease (STD) testing among
      black and Hispanic school-aged young men who have sex with men (YMSM). METHODS:
      Participants were recruited at community-based organizations that serve YMSM in
      New York City, Philadelphia, and San Francisco. Eligible participants were 13- to
      19-year-old black or Hispanic males who reported attraction to or sexual behavior
      with other males and/or identified as gay or bisexual, and attended at least 90
      days of school in the previous 18 months. Participants (N = 415) completed web
      based questionnaires and/or in-depth interviews (N = 32). RESULTS: In the past
      year, 72.0% of questionnaire participants had been tested for HIV, 13.5% of them
      at school or school clinic. Participants reported that they would be more likely
      to get an HIV test if they could be tested close to or at school (34.4%), and
      64.4% would use HIV testing if offered in schools. Most interview participants
      reported willingness to use school-based services if they were offered
      nonjudgmentally, privately, and confidentially by providers with experience
      serving YMSM. CONCLUSION: Schools can provide opportunities to make HIV and STD
      testing accessible to school-aged YMSM, but the services must be provided in ways
      that are comfortable to them.

PMID- 27866392
TI  - Drug-caused deaths in Australian medical practitioners and health-care
      professionals.
AB  - BACKGROUND AND AIMS: There are numerous factors putting health-care professionals
      (HCP) at a higher risk of substance abuse and premature death, including high
      stress jobs, access to controlled substances, long hours of practice and constant
      contact with the critically ill. This study aimed to examine fatal drug toxicity
      in this high-risk cohort, in order to: (1) estimate the rate of drug-caused
      deaths of Australian HCPs; (2) describe the key characteristics of the cohort;
      and (3) examine the relationship between HCP occupation and drug type, or intent.
      DESIGN: Retrospective cohort study. SETTING: The National Coronial Information
      System (NCIS), a database of cases reported to an Australian coroner.
      PARTICIPANTS: A total of 404 drug-caused deaths reported to an Australian coroner
      between 2003 and 2013 involving HCPs (including medical practitioners,
      paramedics, nurses, dentists, psychologists, pharmacists and veterinarians).
      MEASURES: chi2 tests and descriptive statistics were used to examine
      relationships. The primary outcome measures were drug type and intent. Covariates
      included occupation type, mental illness and self-harm. FINDINGS: Females
      comprised nearly two-thirds of the cohort. The highest number of cases involved
      nurses (62.87%) and medical practitioners (18.07%). The mortality rate was
      highest among the veterinary group [confidence interval (CI) = 42.21-58.79]. Most
      were intentional self-harm deaths (50.25%), followed by unintentional deaths
      (37.62%) (CI = 92.15-109.85). Mental illness was common, diagnosed in almost half
      of cases (46.04%), with the majority involving depression (CI = 33.48-44.12).
      Specific drugs were associated significantly with certain professions, such as
      intravenous barbiturates among veterinarians (chi2(7)  = 237.391). A number of
      cases reported additional stressors, such as relationship, work-place or
      financial issues, and drugs were diverted from the work-place in nearly a fifth
      of cases. CONCLUSIONS: Between 2003 and 2013, Australian health-care
      professionals averaged 37 deaths per year attributed to drug toxicity, with a
      mortality rate of nearly five deaths per 1000 employed HCPs. Drug-caused deaths
      among HCPs in Australia commonly involve females in their mid-40s, with a
      diagnosis of mental illness, personal and professional stress and the intent to
      self-harm.

PMID- 27866391
TI  - Adolescent Healthcare Brokering: Prevalence, Experience, Impact, and
      Opportunities.
AB  - BACKGROUND: Limited health literacy disproportionately affects those with limited
      English proficiency (LEP). Parents with LEP might rely on their adolescent
      children to interpret health information. We call this adolescent healthcare
      brokering. This study uncovers the prevalence of brokering, kinds of tasks,
      emotional and academic impact, and desired support. METHODS: We invited 165
      students from health classes (in a community in which 29.8% are foreign-born and
      53.4% speak another language at home) to complete a survey. We used IBM SPSS to
      calculate descriptive statistics. RESULTS: Of the 159 who received parental
      consent and assented, 54.1% (N = 86) assist with healthcare tasks. When
      brokering, 80.2% (N = 69) translate. Most common tasks were talking to a doctor,
      reading prescriptions, and searching on the Internet. Participants were most
      confident reading prescriptions and talking to a doctor and least confident
      finding healthcare services. Among brokers, 29.1% (N = 24) missed school; 33.7%
      did not complete homework. They most wanted to learn about filling out insurance
      forms and talking to doctors. CONCLUSIONS: Despite assurances that children are
      not permitted to interpret, adolescents are acting as healthcare brokers. The
      impact can be academic and emotional. Findings indicate a need for further
      research and support for adolescents who want to learn about healthcare tasks.

PMID- 27866393
TI  - Potentially pathogenic circulating autoantibodies to cardiac troponin are present
      in hemodialysis patients.
AB  - INTRODUCTION: Repetitive dialysis-induced cardiac injury is associated with
      elevated troponin levels, inflammation, and longitudinal reduction in cardiac
      function. Pathogenic autoantibodies to cardiac troponins (cTnAAb) produce
      inflammatory cardiomyopathy in murine models. This study aimed to explore the
      possibility that analogous autoimmune processes might occur in hemodialysis (HD)
      patients, by initially investigating cTnAAb prevalence, and exploring potential
      links with HD-induced myocardial stunning. METHODS: In 130 prevalent HD patients
      from two centers (Derby, UK; Turku, Finland), cTnAAb (immunoassay) and cardiac
      troponins were quantified. Sixty-four patients underwent serial echocardiography
      to assess myocardial stunning. FINDINGS: cTnAAb were present in 7% of patients.
      Dual positivity to cTnAAb and elevated cTn occurred in 3% and 6% for cTnI and
      cTnT, respectively. Patients with cTnAAb had significantly longer dialysis
      vintage (82 vs. 30 months, P = 0.024), higher cTnT (0.1 vs. 0.05 pg/mL, P =
      0.04), cTnI (0.02 vs. 0.01 pg/mL, P = 0.029), and free PAPP-A (6.4 vs. 3.3 mIU/L,
      P = 0.038). DISCUSSION: This is the first description of cTnAAb in HD patients,
      which raises the possibility that longitudinal exposure to repetitive HD-induced
      cardiac injury may lead to further autoimmune-based myocardial insult.

PMID- 27866395
TI  - [Best Medical Rreatment of Vascular Diseases: Which future?]

PMID- 27866397
TI  - Left Partial Anomalous Pulmonary Venous Return and Mitral Stenosis in an Adult.
AB  - Partial anomalous pulmonary venous return (PAPVR) is a relatively common
      congenital cardiac malformation in which one to three pulmonary veins drain to a
      systemic vein, the right atrium or the coronary sinus, resulting in a left-to
      right shunt and the risk of developing pulmonary hypertension (PHT). It is
      frequently associated to other congenital cardiac defects (mainly atrial septal
      defect) but seldom associated with acquired cardiac disease, and normally
      involves the right lung. When it involves the left lung, the surgical correction
      in children is normally performed without prosthetic material. The authors report
      a case of associated mitral stenosis and left PAPVR corrected with comissurotomy
      and extra-anatomic derivation with a synthetic vascular graft.

PMID- 27866394
TI  - Repeated otilonium bromide administration prevents neurotransmitter changes in
      colon of rats underwent to wrap restraint stress.
AB  - Otilonium bromide (OB) is a spasmolytic drug successfully used for the treatment
      of irritable bowel syndrome (IBS). Its efficacy has been attributed to the block
      of L- and T-type Ca2+ channels and muscarinic and tachykinin receptors in the
      smooth muscle. Furthermore, in healthy rats, repeated OB administration modified
      neurotransmitter expression and function suggesting other mechanisms of action.
      On this basis, we investigated whether repeated OB treatment prevented the
      functional and neurochemical changes observed in the colon of rats underwent to
      wrap restrain stress (WRS) a psychosocial stressor considered suitable to
      reproduce the main IBS signs and symptoms. In control, WRS and OB/WRS rats
      functional parameters were measured in vivo and morphological investigations were
      done ex vivo in the colon. The results showed that OB counteracts most of the
      neurotransmitters changes caused by WRS. In particular, the drug prevents the
      decrease in SP-, NK1r-, nNOS-, VIP-, and S100beta-immunoreactivity (IR) and the
      increase in CGRP-, and CRF1r-IR. On the contrary, OB does not affect the increase
      in CRF2r-IR neurons observed in WRS rats and does not interfere with the mild
      mucosal inflammation due to WRS. Finally, OB per se increases the Mr2 expression
      in the muscle wall and decreases the number of the myenteric ChAT-IR neurons.
      Functional findings show a significantly reduction in the number of spontaneous
      abdominal contraction in OB treated rats. The ability of OB to block L-type Ca2+
      channels, also expressed by enteric neurons, might represent a possible mechanism
      through which OB exerts its actions.

PMID- 27866396
TI  - [Patency of Coronary Artery Bypass Graft].
AB  - INTRODUCTION: Coronary heart disease is the leading cause of death and disability
      in the U.S. and Europe. When significant, the coronary disease can be treated
      medically or surgically. The medical treatment is performed in the
      catheterization laboratory and consists in the re-permeabilization of the
      coronary arteries by percutaneous approach, whereas the surgical myocardial
      revascularization consists in performing aorto-coronary bypass using arterial or
      venous conduits. OBJECTIVE: This study is sought to assess the patency and
      longevity of bypass in patients requiring new catheterization after surgery for
      recurrence of ischemic heart disease and to evaluate its relationship with
      factors such as the type of bypass, cardiovascular risk factors and left
      ventricular ejection fraction. METHODS: This study retrospectively analysed a
      sample of 260 surgically revascularized patients who required a new
      catheterization at the Hospital of Vila Nova de Gaia - Espinho between 2007 and
      2012, for recurrence of ischemic heart disease. The degree of patency of the
      bypass was evaluated and sought a relationship with other variables such as
      gender, age, cardiovascular risk factors, left ventricular ejection fraction, the
      time interval between bypass surgery and the new catheterization. RESULTS: The
      patency of the arterial bypass using the left internal mammary artery proved to
      be superior to the venous conduit bypass. There was no statistically significant
      relationship between the patency of the bypass, the cardiovascular risk factors
      and the left ventricle ejection fraction. CONCLUSION: In this study we found a
      greater patency of the arterial bypass compared to the venous bypass.

PMID- 27866398
TI  - [Anorexia and Weight Loss as First Symptoms of a Solitary Fibrous Tumor of the
      Pleura].
AB  - We report the clinical case of a 66 year-old woman with anorexia and weight loss,
      in whom a giant mass was found in the left pulmonary field. A computorized
      tomography guided fine-needle biopsy established the diagnosis of a solitary
      fibrous tumor of the pleura. Surgical resection of a 2655 grams of tumor mass was
      performed and the pathological examination confirmed the diagnosis. Nine months
      after surgery, the patient remained free of symptoms and with no evidence of
      disease recurrence. Solitary fibrous tumor of the pleura is a rare entity with
      mesenchymal origin. Although most solitary fibrous tumors of the pleura are
      benign, they possess a malignant potential and thus should be totally excised.
      Diagnosis is generally incidental, being the majority of the patients
      asymptomatic. However, extrinsic compression of the solitary fibrous pleural
      tumor on lung parenchyma may cause symptoms, from which the commonest are cough,
      dyspnea, and chest pain. The clinical presentation, suggestive of a consumptive
      and malignant disease reinforced the heterogeneity of this disease and the
      singularity of this clinical case, thus justifying its presentation.

PMID- 27866399
TI  - Thoracoscopic Pleural Abrasion in Neonatal Recurrent Pneumothorax.
AB  - Recurrent pneumothorax is a rare neonatal condition and there are few cases
      reporting surgical treatment, mainly based on adult studies. We present a male,
      term newborn that after four recurrent spontaneous pneumothorax (treated with
      pleural needle aspiration and drains) underwent thoracoscopic mechanical pleural
      abrasion. There were no post-operatory complications and no recurrence reported
      until the second year of life. We believe that this technique is safe and
      effective and may play an important role in these cases.

PMID- 27866400
TI  - [Deep Venous Thrombosis in Emergency Care: From Clinical Suspicion to Correct
      Diagnosis].
AB  - AIM: Retrospective analysis of suspected deep venous thrombosis (DVT) of the
      lower limbs admitted to an emergency unit and subsequently scanned in the
      vascular lab. METHODS: Clinical and demographic details of patients were
      retrieved from clinical files and collected in a database. The statistical
      software SPSS was used for statistical analysis. RESULTS: Between January 2011
      and September 2013, 407 venous scans were performed for ruling out DVT. Two
      hundred sixty-nine (66%) patients were female. Average age was 60.1 years-old (16
      93). One hundred thirty-four scans (32.9%) were positive for the diagnosis of
      recent DVT (simultaneous DVT and superficial thrombophlebitis in six patients of
      this group). In 194 exams (47.6%) there was any sign of venous thrombosis,
      whether recent or remote. The remaining cases showed up signs of remote DVT in 22
      (5.4%) patients, and superficial thrombophlebitis in 50 (12.2%) patients.
      CONCLUSION: Suspected DVT was confirmed in only a third of patients, using
      ultrasound scan. Local implementation of guidelines for the evaluation of
      patients with suspected DVT may reduce the amount of unnecessary scans.

PMID- 27866402
TI  - [Subclavian Steal Syndrome and Cerebral Hypoperfusion during Hemodialysis: A case
      report].
AB  - Subclavian steal syndrome is caused by retrograde vertebral artery flow
      "stealing" vertebrobasilar perfusion. We report the clinical case of a 53 year
      old dialysis dependent woman with several cardiovascular risk factors, who had
      episodes of vertebrobasilar insufficiency and resting pain of the left upper
      extremity, during hemodialysis sessions, through a left arm brachiobasilic
      arteriovenous fistula. Noninvasive studies demonstrated a preoclusive stenosis at
      the origin of left subclavian artery, together with a stenosis on the left
      internal carotid artery superior to 70% and reversion of flow in the left
      vertebral artery. The patient underwent endarterectomy and Dacron patch
      angioplasty of the left internal carotid artery and carotid-subclavian ePTFE
      bypass, with total resolution of the previously described clinical presentation.

PMID- 27866401
TI  - [Primary Aorto-enteric Fistula Related to an Aortic Pseudo Aneurysm].
AB  - : Primary aorto-enteric fistula is a very rare entity, with a high mortality.
      Direct aortic reconstruction is the preferred treatment, with extra-anatomic
      revascularization regarded as an alternative. Despite somehow promising results,
      the role of endovascular exclusion is still under scrutiny. CASE REPORT: Male
      patient, 80 years old, with a history of Micobacterium bovis infection one year
      ago, and two episodes of gastrointestinal bleeding in the last month. He
      presented with abdominal pain and hematochezia, was hypotensive and digested
      blood was found in the nasogastric tube. Anemia (Hb 7,3g/dL) was the only
      bloodwork remark. Upper and lower endoscopies reported no bleeding nor suspect
      lesions. Angio-CT showed a pseudo aneurysm of the infra-renal aorta, adherent to
      the third portion of the duodenum, with findings suggestive of an aorto-enteric
      fistula; it also showed a thrombosed false aneurysm related to the aorta and left
      iliac artery. None of these CT findings were reported in a CT done one year
      before. A right axillo-femoral bypass and crossover femoro-femoral bypass were
      done, before laparotomy, duodenal repair with jejunal patch and aortic and iliac
      arteries suture interruption. Good clinical outcome, with discharge from hospital
      on the 11th post-operative day. One year afterwards no vascular or
      gastrointestinal events were noticed. No positive microbiological cultures were
      obtained. CONCLUSION: The history of previous Micobacterium infection and the
      absence of the CT findings one year before this event support the aortic
      infection as the most likely cause for the fistula, emphasizing the rarity of
      this case.

PMID- 27866403
TI  - [Occlusion of Peripheral Bypass - Changing of an Institutional Paradigm].
AB  - The vast majority of renovascular hypertension is treated nowadays resorting to
      endovascular procedures (angioplasty/stenting). We report a case of malignant
      hypertension derived from bilateral ostial renal artery occlusion with unfit
      anatomy for endovascular correction. The patient maintained assymptomatic with
      controlled arterial tension at the thirteenth yeah of follow-up, due to a
      splenorenal bypass. A review of the literature and this surgery indications is
      discussed.

PMID- 27866404
TI  - Current Era of Minimally Invasive Aortic Valve Replacement.

PMID- 27866405
TI  - Occupation and mesothelioma in Sweden: updated incidence in men and women in the
      27 years after the asbestos ban.
AB  - OBJECTIVES: We updated the Swedish component of the Nordic Occupational Cancer
      (NOCCA) Study through 2009 in order to investigate the incidence of mesothelioma
      of the peritoneum and pleura in both genders, and explored occupational exposures
      that may be associated with mesothelioma. METHODS: The Swedish component of the
      NOCCA Study includes 6.78 million individuals. Data from this cohort were linked
      to the population-based Swedish Cancer Registry and Swedish Total Population
      Registry for three periods between 1961 and 2009, and then further linked to the
      Swedish NOCCA job-exposure matrix, which includes 25 carcinogenic substances and
      the corresponding exposure levels for 280 occupations. Multivariate analysis was
      used to calculate standardized incidence ratios (SIRs) for mesothelioma of the
      peritoneum and pleura by gender, occupational category, carcinogenic substance,
      and for multiple occupational exposures simultaneously. RESULTS: A total of 3,716
      incident mesotheliomas were recorded (21.1% in women). We found a significantly
      increased risk of mesothelioma in 24 occupations, as well as clear differences
      between the genders. Among men, increased risks of mesothelioma of the pleura
      were observed in male-dominated occupations, with the greatest elevation of risk
      among plumbers (SIR, 4.99; 95% confidence interval, 4.20 to 5.90). Among women,
      increased risks were observed in sewing workers, canning workers, packers,
      cleaners, and postal workers. In multivariate analysis controlling for multiple
      occupational exposures, significant associations were only observed between
      asbestos exposure and mesothelioma. CONCLUSIONS: Asbestos exposure was associated
      with mesothelioma incidence in our study. The asbestos ban of 1982 has yet to
      show any clear effect on the occurrence of mesothelioma in this cohort. Among
      women, the occupations of canning workers and cleaners showed increased risks of
      mesothelioma of the pleura without evidence of asbestos exposure.

PMID- 27866406
TI  - Prevalence of factors related to active reproductive health behavior: a cross
      sectional study Indonesian adolescent.
AB  - OBJECTIVES: Complex and diverse factors are related to reproductive health (RH)
      behavior among adolescents according to the social and cultural context of each
      countries. This study examined the prevalence of active RH and factors related to
      active RH behavior among Indonesian adolescents. METHODS: A cross-sectional study
      was conducted among 1,040 of students who were selected through a multi-stage
      random sampling technique. A self-administered questionnaire was developed,
      including the World Health Organization Illustrative Questionnaire for Interview
      Surveys with Young People, pubertal development scale, and sexual activity scale,
      modified in accordance to the Indonesian context. The data were analyzed using
      descriptive and comparative statistics, as well as logistic regression analyses.
      RESULTS: The prevalence of active RH behavior were more higher in boys (56.6%;
      95% confidence interval [CI], 50.6% to 62.6%) than in girls (43.7%; 95% CI, 37.6%
      to 49.8%). Negative attitudes towards RH were a factor related to active RH
      behavior in both boys and girls. Smoking and kind relationship envisioned before
      marriage (pacaran [courtship] and nikah siri [non-registered marriage]) were
      factors related to active RH behavior in boys; whereas the absence of access to
      information on substance abuse was an additional factor in girls. Moreover, an
      interaction was found between access to information on development and smoking
      (boys) and attitudes on RH (girls) as independent variables associated with
      active RH behavior. CONCLUSIONS: Sex education for adolescents in Indonesia,
      particularly in the context of a health promotion program, should be developed
      based on prevalent social, cultural, and religious values to prevent active RH
      behavior. Such programs should focus on the kind of relationship envisioned
      before marriage and smoking for boys and access to information on subtance abuse
      for girls.

PMID- 27866407
TI  - Forecasting and prediction of scorpion sting cases in Biskra province, Algeria,
      using a seasonal autoregressive integrated moving average model.
AB  - OBJECTIVES: The aims of this study were to highlight some epidemiological aspects
      of scorpion envenomations, to analyse and interpret the available data for Biskra
      province, Algeria, and to develop a forecasting model for scorpion sting cases in
      Biskra province, which records the highest number of scorpion stings in Algeria.
      METHODS: In addition to analysing the epidemiological profile of scorpion stings
      that occurred throughout the year 2013, we used the Box-Jenkins approach to fit a
      seasonal autoregressive integrated moving average (SARIMA) model to the monthly
      recorded scorpion sting cases in Biskra from 2000 to 2012. RESULTS: The
      epidemiological analysis revealed that scorpion stings were reported continuously
      throughout the year, with peaks in the summer months. The most affected age group
      was 15 to 49 years old, with a male predominance. The most prone human body areas
      were the upper and lower limbs. The majority of cases (95.9%) were classified as
      mild envenomations. The time series analysis showed that a (5,1,0)*(0,1,1)12
      SARIMA model offered the best fit to the scorpion sting surveillance data. This
      model was used to predict scorpion sting cases for the year 2013, and the fitted
      data showed considerable agreement with the actual data. CONCLUSIONS: SARIMA
      models are useful for monitoring scorpion sting cases, and provide an estimate of
      the variability to be expected in future scorpion sting cases. This knowledge is
      helpful in predicting whether an unusual situation is developing or not, and
      could therefore assist decision-makers in strengthening the province's prevention
      and control measures and in initiating rapid response measures.

PMID- 27866408
TI  - Prescribing patterns for attention deficit hyperactivity disorder medications
      among children and adolescents in Korea, 2007-2011.
AB  - OBJECTIVES: This study analyzed the prevalence of attention deficit hyperactivity
      disorder (ADHD) medication use among children and adolescents in Korea between
      January 1, 2007 and December 31, 2011. METHODS: Using the Korea National Health
      Insurance claims database, we identified patients between one and 17 years of age
      who had at least one medical claim for the diagnosis of ADHD (International
      Classification of Diseases, 10th revision: F90.0). The annual prevalence of ADHD
      diagnoses was calculated, using national census data from Statistics Korea on the
      population aged between one and 17 years as the denominator. The prevalence was
      age-standardized using the 2010 population as the standard population. The number
      of patients who were treated with methylphenidate and/or atomoxetine and the
      prevalence of total patients with ADHD that were treated with either drug were
      also calculated for each year. All analyses were stratified according to gender
      and age group (1-5 years, 6-12 years, and 13-17 years). RESULTS: The number of
      patients diagnosed with ADHD increased from 72,704 persons (0.71%) in 2007 to
      85,468 persons (0.93%) in 2011. The annual age-standardized prevalence of ADHD
      diagnoses increased from 0.67% in 2007 to 0.94% in 2011. The prevalence of
      methylphenidate use among children and adolescents with ADHD decreased from
      73.91% in 2007 to 70.33% in 2011, whereas that of atomoxetine use increased from
      5.77% in 2009 to 13.09% in 2011. CONCLUSIONS: While methylphenidate remains the
      most commonly prescribed ADHD drug, the use of atomoxetine has increased.

PMID- 27866409
TI  - Child migration: from social determinants of health to the development agenda and
      beyond.

PMID- 27866410
TI  - Distress, depression and anxiety among persons seeking HIV testing.
AB  - We investigated psychological distress and symptoms of depression and anxiety
      among 485 South Africans seeking HIV testing. The mean scores of the sample were
      45.78 (SD = 16.81) on the Hopkins Symptom Checklist; 15.8 (SD = 12.4) on the Beck
      Depression Inventory and 12.44 (SD = 13.00) on the Beck Anxiety Inventory, which
      fell in the elevated, mild and low ranges on these instruments, respectively. For
      more than a third of participants, symptoms of depression and clinically
      significant distress were at least moderate and in some cases severe, indicating
      that they may have benefitted from psychological help. We make the case that
      symptoms of depression and distress are common among persons seeking HIV testing
      and are therefore not a consequence of an HIV-positive test result.

PMID- 27866411
TI  - Evaluation of the ERIC-PCR as a probable method to differentiate Avibacterium
      paragallinarum serovars.
AB  - Infectious coryza, an upper respiratory tract disease in chickens, caused by
      Avibacterium paragallinarum, leads to huge economic losses. The disease is
      controlled through vaccination; but vaccination efficacy is dependent on correct
      identification of the infecting serovar, as limited cross-protection is reported
      amongst some serovars. Current identification methods include the
      heamagglutination inhibition test, which is demanding and could be subjective. To
      overcome this, molecular typing methods proposed are the Multiplex polymerase
      chain reaction (PCR) and Restriction Fragment Length Polymorphism-PCR, but low
      reproducibility is reported. Enterobacterial Repetitive Intergenic Consensus
      (ERIC)-PCR has been suggested for molecular groupings of various bacterial
      species. This study focuses on evaluating the ERIC-PCR as a probable method to
      differentiate between different Av. paragallinarum serovars by grouping with
      reference isolates, based on clonal relations. The ERIC-PCR was performed on 12
      reference isolates and 41 field isolates originating from South Africa and South
      America. The data indicate that the ERIC-PCR is not ideal for the differentiation
      or for molecular typing of Av. paragallinarum serovars, as no correlation is
      drawn upon comparison of banding patterns of field isolates and reference
      strains. However, the results do indicate isolates from the same origin sharing
      unique banding patterns, indicating potential clonal relationship; but when
      compared to the reference isolates dominant in the specific area, no correlation
      could be drawn. Furthermore, although the ERIC-PCR serves a purpose in
      epidemiological studies, it has proved to have little application in
      differentiating amongst serovars of Av. paragallinarum and to group untyped field
      strains with known reference strains.

PMID- 27866412
TI  - Failing to deliver established quality treatment for cervical cancer: what is
      going on and how can we improve it?

PMID- 27866413
TI  - Disbalance of calcium regulation-related genes in broiler hearts induced by
      selenium deficiency.
AB  - Dietary selenium (Se) deficiency may influence the calcium (Ca) homeostasis in
      broilers. Our objective was to investigate the effects of Se deficiency on Ca
      regulation-related genes in broiler hearts. In the present study, 1-day-old
      broilers were fed either a commercial diet (as control group) with 0.15 mg/kg Se
      or a Se-deficient diet (as L group) with 0.033 mg/kg Se for 35 days. We examined
      the mRNA expression levels of 15 Ca regulation-related genes (ITPR 1, ITPR 2,
      ITPR3, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S, TRPC1, TRPC3, stromal
      interacting molecule 1, ORAI1, calmodulin (CaLM) and calreticulin (CRT) in
      broiler hearts. Then, Kyoto Encyclopedia of Genes and Genomes analysis, protein
      protein interactions (PPI) analysis and correlation analysis were performed to
      analyse the relationships between these genes. The results showed that the mRNA
      expression levels of ITPR 1, ITPR 2, RyR2, RyR3, SERCA1s, SLC8A1, PMCA1, CACNA1S,
      CaLM and CRT were generally decreased by Se deficiency, while mRNA expression
      levels of TRPC1, TRPC3, stromal interacting molecule 1, ORAI1 and ITPR3 were
      increased by Se deficiency. Kyoto Encyclopedia of Genes and Genomes and PPI
      analysis showed that these Ca regulation-related genes are involved in the Ca
      signalling pathway and a total of 15 PPIs with a combined score of >0.4 were
      obtained. In conclusion, the results demonstrated that Se deficiency might cause
      heart injury via modulating the Ca-related pathway genes, and then induce Ca2+
      overload in the heart of broilers.

PMID- 27866414
TI  - Chemerin level in pregnancies complicated by preeclampsia and its relation with
      disease severity and neonatal outcomes.
AB  - The aims of this prospective study were to detect maternal serum chemerin level
      in patients with preeclampsia and investigate its association with disease
      severity and neonatal outcomes. Maternal serum chemerin levels were significantly
      elevated in severe preeclamptic women (394.72 +/- 100.01 ng/ml) compared to mild
      preeclamptic women (322.11 +/- 37.60 ng/ml) and healthy pregnant women (199.96 +/
      28.05 ng/ml) (p = .001). Maternal serum chemerin levels were positively
      correlated with systolic and diastolic blood pressure, C-reactive protein levels,
      homeostasis model assessment of insulin resistance, proteinuria, AST, ALT, and
      duration of hospitalisation. Gestational week at delivery, birthweight, and APGAR
      scores at 1 and 5 min were negatively correlated with maternal serum chemerin
      level. A maternal serum chemerin level of >252.0 ng/ml indicated preeclampsia
      with 95.5% sensitivity and 95.7% specificity. There was a positive correlation
      between maternal serum chemerin level and severity of preeclampsia. Additionally,
      adverse neonatal outcomes were significantly associated with high maternal serum
      chemerin levels.

PMID- 27866415
TI  - Teachers' perceptions of implementation of aided AAC to support expressive
      communication in South African special schools: a pilot investigation.
AB  - Although the provision of assistive technology for students with disabilities has
      been mandated in South African education policy documents, limited data are
      available on the implementation of aided augmentative and alternative
      communication (AAC) in classrooms. This pilot investigation used a concurrent
      mixed-methods survey design to determine the extent to which aided AAC was
      implemented to foster students' expressive communication in preschool to Grade 3
      classrooms in special schools from six urban school districts in the Gauteng (the
      smallest, most affluent and most densely populated of the nine South African
      provinces), and also obtained teachers' perceptions of this process. A total of
      26 teachers who taught students who used aided AAC for expression participated.
      Although there is evidence of provision and also implementation of aided AAC in
      classrooms, various limitations still exist. Teachers identified an array of
      factors that influenced the implementation of aided AAC, including those related
      to themselves, the classroom context, the characteristics of aided AAC, students
      using AAC, and other stakeholders. These factors are discussed in the light of
      international literature as well as the local context, and are used as a basis to
      suggest a research agenda for AAC in the South African education system.

PMID- 27866416
TI  - How active are patients in setting goals during rehabilitation after stroke? A
      qualitative study of clinician perceptions.
AB  - PURPOSE: We investigated stroke rehabilitation clinician's perceptions of the
      patient as an active partner in setting goals within stroke rehabilitation and
      factors that influence patient engagement. METHODS: Semi-structured interviews,
      subject to general inductive analysis with 20 Clinicians' working in three UK
      based stroke rehabilitation teams (one in-patient ward and two community based
      rehabilitation teams). RESULTS: There were three key themes that impacted on the
      patients active involvement in setting goals for rehabilitation after stroke:
      Patient barriers to goal setting (knowledge of the patient and family, who is the
      patient and the stroke's impact); How we work as a team (the role of the patient
      in setting goals, the effect of clinician attributes on goal setting); and How
      systems impact goal setting (goal-setting practice, home versus hospital, and
      professional/funder expectations of clinicians'). CONCLUSIONS: Goal setting
      served a range of different, sometimes conflicting, functions within
      rehabilitation. Clinicians' identified the integral nature of goals to engage and
      motivate patients and to provide direction and purpose for rehabilitation.
      Further, there was an identified need to consider the impact of prioritizing
      clinician-derived goals at the expense of patient-identified goals. Lastly the
      reliance on the SMART goal format requires further consideration, both in terms
      of the proposed benefits and whether they disempower the patient during
      rehabilitation. Implications for rehabilitation Goal setting is often promoted as
      a relatively simple, straightforward way to structure interactions with patients
      Patient-related factors together with resourcing constraints are significant
      barriers to patient-centered goal setting, particularly during inpatient
      rehabilitation Clinicians need to have pragmatic tools that can be integrated
      into practice to ensure that goal-setting practice can be maximized for patients
      with different intrinsic characteristics.

PMID- 27866417
TI  - BODIPY-conjugated chitosan nanoparticles as a fluorescent probe.
AB  - Recently, development of fluorescent nanoparticle-based probes for various
      bioimaging applications has attracted great attention. This work aims to develop
      a new type fluorescent nanoparticle conjugate and evaluate its cytotoxic effects
      on A549 and BEAS 2B cell lines. Throughout the study, ionically crosslinked
      chitosan nanoparticles (CNs) were conjugated with carboxylated 4,4-difluoro-4
      bora-3a,4a-diaza-s-indacene (BODIPY-COOH). The results of conjugates (BODIPY-CNs)
      were investigated with regard to their physic-chemical, optical, cytotoxic
      properties and cellular internalization. The morphology of BODIPY-CNs was found
      to be spherical in shape and quite uniform having average diameter of 70.25 +/-
      11.99 nm. Cytotoxicty studies indicated that although BODIPY-COOH itself was
      quite toxic on both A549- and BEAS 2B-treated cells, CNs increased the cell
      viability of both cell lines via conjugation to BODIPY-COOH fluorescent molecule
      up to 67% for A549 and 74% for BEAS 2B cells. These results may suggest a
      possible utilization of the new fluorescent nanoparticle-based probe for
      bioimaging in biology and medicine.

PMID- 27866418
TI  - Microinvasive squamous carcinoma of neovagina created with peritoneal flap
      (Davidov): Case report and literature review.
AB  - Carcinoma of the vagina is a rare disease, and it is even more rare when it
      appears in a neovagina, having its incidence and optimum treatment constantly
      discussed. The aim of this article was to review the cases described in the
      currently available literature and describe the second documented case of
      carcinoma in a neovagina created with peritoneal flaps, and also list the
      possible pathways and risk factors for its development. The case we present is a
      49-year-old female who after undergoing a laparoscopic colpectomy of the upper
      two-thirds of the vagina, with an immediate reconstruction with peritoneal flaps
      by laparoscopy, at a 4 months follow up presented a focal microinvasive squamous
      carcinoma in the vault of the neovagina. After reviewing the literature, we
      conclude that excisional treatment is the preferable option to avoid the
      progression to an invasive carcinoma. However, this case demonstrates the
      importance of the necessity to do regular cito-vulvovaginoscopic examinations
      after the complete surgical treatment because of the chance of persistent or
      recurrent lesions on the transplanted tissue.

PMID- 27866419
TI  - Evidence for Impact and Impact of Evidence.

PMID- 27866421
TI  - The development of 1,3-diphenylisobenzofuran as a highly selective probe for the
      detection and quantitative determination of hydrogen peroxide.
AB  - 1,3-Diphenylisobenzofuran (DPBF) has been developed as a selective probe for the
      detection and quantitative determination of hydrogen peroxide in samples
      containing different reactive nitrogen and oxygen species (RNOS). DPBF is a
      fluorescent probe which, for almost 20 years, was believed to react in a highly
      specific manner toward some reactive oxygen species (ROS) such as singlet oxygen
      and hydroxy, alkyloxy or alkylperoxy radicals. Under the action of these
      individuals DPBF has been rapidly transformed to 1,2-dibenzoylbenzene (DBB). In
      order to check if DPBF can act as a unique indicator of the total amount of
      different RNOS, as well as oxidative stress caused by an overproduction of these
      individuals, a series of experiments was carried out, in which DPBF reacted with
      peroxynitrite anion, superoxide anion, hydrogen peroxide, hypochlorite anion, and
      anions commonly present under biological conditions, namely nitrite and nitrate.
      In all cases, except for hydrogen peroxide, the product of the reaction is DBB.
      Only under the action of H2O2 9-hydroxyanthracen-10(9H)-one (oxanthrone) is
      formed. This product has been identified with the use of fluorescence
      spectroscopy, NMR spectroscopy, high performance liquid chromatography coupled
      with mass spectrometry, infrared spectroscopy, elemental analysis, and cyclic
      voltammetry (CV). A linear relationship was found between a decrease in the
      fluorescence intensity of DPBF and the concentration of hydrogen peroxide in the
      range of concentrations of 0.196-3.941 mM. DPBF responds to hydrogen peroxide in
      a very specific way with the limits of detection and quantitation of 88 and 122.8
      MUM, respectively. The kinetics of the reaction between DBBF and H2O2 was also
      studied.

PMID- 27866420
TI  - Cancer stem cell-targeted therapeutics and delivery strategies.
AB  - INTRODUCTION: Cancer initiating or stem cells (CSCs) are a small population of
      cells in the tumor mass, which have been reported to be present in different
      types of cancers. CSCs usually reside within the tumor and are responsible for
      reoccurrence of cancer. The imprecise, inaccessible nature and increased efflux
      of conventional therapeutic drugs make these cells resistant to drugs. We discuss
      the specific markers for identification of these cells, role of CSCs in
      chemotherapy resistance and use of different therapeutic means to target them,
      including elucidation of specific cell markers, exploitation of different
      signaling pathways and use of nanotechnology. Area covered: This review covers
      cancer stem cell signaling which are used by these cells to maintain their
      quiescence, stemness and resistant phenotype, distinct cell surface markers,
      contribution of these cells in drug resistance, inevitability to cure cancer and
      use of nanotechnology to overcome this hurdle. Expert opinion: Cancer stem cells
      are the main culprit of our failure to cure cancer. In order to cure cancer along
      with other cells types in cancer, cancer stem cells need to be targeted in the
      tumor bed. Nanotechnology solutions can facilitate clinical translation of the
      therapeutics along with other emerging technologies to cure cancer.

PMID- 27866422
TI  - Mapping the rehabilitation interventions of a community stroke team to the
      extended International Classification of Functioning, Disability and Health Core
      Set for Stroke.
AB  - PURPOSE: This study aim was to evaluate whether the Extended International
      Classification of Functioning, Disability and Health Core Set for Stroke captured
      the interventions of a community stroke rehabilitation team situated in a large
      city in New Zealand. It was proposed that the results would identify the
      contribution of each discipline, and the gaps and differences in service
      provision to Maori and non-Maori. Applying the Extended International
      Classification of Functioning, Disability and Health Core Set for Stroke in this
      way would also inform whether this core set should be adopted in New Zealand.
      METHOD: Interventions were retrospectively extracted from 18 medical records and
      linked to the International Classification of Functioning, Disability and Health
      and the Extended International Classification of Functioning, Disability and
      Health Core Set for Stroke. The frequencies of linked interventions and the
      health discipline providing the intervention were calculated. RESULTS: Analysis
      revealed that 98.8% of interventions provided by the rehabilitation team could be
      linked to the Extended International Classification of Functioning, Disability
      and Health Core Set for Stroke, with more interventions for body function and
      structure than for activities and participation; no interventions for emotional
      concerns; and limited interventions for community, social and civic life. Results
      support previous recommendations for additions to the EICSS. CONCLUSIONS: The
      results support the use of the Extended International Classification of
      Functioning, Disability and Health Core Set for Stroke in New Zealand and
      demonstrates its use as a quality assurance tool that can evaluate the scope and
      practice of a rehabilitation service. Implications for Rehabilitation The
      Extended International Classification of Functioning Disability and Health Core
      Set for Stroke appears to represent the stroke interventions of a community
      stroke rehabilitation team in New Zealand. As a result, researchers and
      clinicians may have increased confidence to use this core set in research and
      clinical practice. The Extended International Classification of Functioning
      Disability and Health Core Set for Stroke can be used as a quality assurance tool
      to establish whether a community stroke rehabilitation team is meeting the
      functional needs of its stroke population.

PMID- 27866424
TI  - Image-guided thermal ablation might be a way to compensate for image deriving
      cancer overdiagnosis.

PMID- 27866423
TI  - Risk factors for bone metastasis in completely resected non-small-cell lung
      cancer.
AB  - AIM: We assessed risk factors for bone metastasis in patients with completely
      resected non-small-cell lung cancer (NSCLC). MATERIALS & METHODS: A total of 374
      NSCLC patients who had undergone a complete resection from January 2008 to May
      2012 were included in this retrospective study. The Kaplan-Meier method and
      multivariate Cox regression analysis were used to evaluate risk factors for bone
      metastasis. RESULTS: A total of 47 (47/374; 12.6%) patients developed bone
      metastasis up until the last follow-up time. The patients with bone metastasis
      included 33 adenocarcinoma patients and 6 (4.9%) squamous cell carcinoma patients
      (p = 0.001). There were 17 (10.2%) patients with pathological stage (P-stage) I
      disease, 9 (9.5%) patients with P-stage II disease and 21 (18.8%) patients with P
      stage III disease (p = 0.007) among all the bone metastasis patients. For
      patients without or with bone metastasis, the overall survival ratio at 3 years
      was 71.6% compared with 46.8% (p < 0.0001), respectively. CONCLUSION:
      Adenocarcinoma and P-stage III disease were related to a high risk of bone
      metastasis.

PMID- 27866425
TI  - The role of physical status versus mental status in predicting the quality of
      life of patients with lumbar disk herniation.
AB  - PURPOSE: To explore the role of physical status versus mental status in
      predicting the quality of life (QOL) of patients with lumbar disk herniation
      (LDH). METHOD: In this correlative study 51 patients with LDH were recruited in
      their conservative stage of treatment. After profiling their physical status, all
      participants reported about pain level (according to VAS), pain perception using
      the Pain Catastrophizing Scale (PCS), and disability level (according to Oswestry
      Low Back Pain Disability Questionnaire). Their mental status was evaluated using
      the Spielberger's State-Trait Anxiety Inventory (STAI) and the Beck Depression
      Inventory (BDI-II). Their QOL was evaluated by the World Health Organization
      Quality of Life Questionnaire, brief version (WHOQOL-BREF). RESULTS: Physical
      status/disability level correlated with anxiety and depression. While Physical
      status predicted physical QOL, mental status, and mainly anxiety and depression
      were the significant predictors of psychological, social, and environmental QOL.
      CONCLUSIONS: Mental status may play a significant role in reducing most QOL
      domains among patients with LDH. The evaluation and intervention process should
      consider both physical and mental status and their relation to the person's QOL.
      Since QOL is a major parameter in determining intervention type and success this
      elaborated perspective may contribute to the intervention planning and outcomes.
      Implications for rehabilitaion A significant mental distress may accompany the
      physical disability of patients with LDH. The role of this mental distress in
      reducing the QOL of patients with LDH may be greater than that of their physical
      disability. The evaluation and intervention for patients with LDH should refer to
      both physical and mental status and explore their impacts on quality of life in
      order to elevate intervention success.

PMID- 27866426
TI  - Comparative study on the induction of complex genomic alterations after exposure
      of mammalian cells to carboplatin and oxaliplatin.
AB  - Metal complexes are still broadly used as the first line of the treatment for
      different types of tumors nowadays. Carboplatin and oxaliplatin were authorized
      for clinical use, even though there is little information on the mutagenic
      profile associated to their usage. This study evaluated the cytostatic effects
      and the induction of complex genomic alterations after 24-h treatment of CHO-K1
      cells to concentrations of 12.5-800 MUM of carboplatin and oxaliplatin in the
      cytokinesis-block micronucleus assay (CBMN-Cyt). The results demonstrated that
      carboplatin and oxaliplatin significantly increased the frequency of micronuclei
      (MN), nucleoplasmatic bridges (NPBs), and nuclear buds (NBUDs). On one hand,
      oxaliplatin induces significantly more chromosomal abnormalities than carboplatin
      at concentrations of 12.5 and 25 MUM. On the other hand, carboplatin, in cells
      exposed to concentrations of 50 and 100 MUM, is more efficient than oxaliplatin
      in the induction of chromosomal instability events. Both drugs cause significant
      reduction in the cytokinesis-block proliferation index, demonstrating their
      cytostatic effects at concentrations 50-800 MUM. The results of this study shed
      more light on the characterization of biological effects associated with the
      exposure to carboplatin and oxaliplatin.

PMID- 27866427
TI  - Image-guided thermal ablation might be a way to compensate for image deriving
      cancer overdiagnosis: Author reply.

PMID- 27866429
TI  - CD99 refers to the activity of inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD), composed of Crohn's disease (CD)
      and ulcerative colitis (UC), is an inflammatory autoimmune disease. CD99 has been
      reported to participate in migration of leukocytes and T cell activation.
      However, the roles of CD99 in IBD are obscure. MATERIALS AND METHODS: CD99
      expression was examined in peripheral blood mononuclear cells (PBMCs) and
      inflamed mucosa from IBD patients by qRT-PCR. Serum TNF-alpha and IL-17A levels
      were detected by ELISA. Correlations of CD99 expression with TNF-alpha, IL-17A,
      Crohn's disease activity index (CDAI), simple endoscopic score for CD (SES-CD),
      Mayo index, and Truelove grading were performed by Pearson's correlation.
      RESULTS: CD99 expression was increased in PBMCs and inflamed mucosa from active
      CD and UC patients, and CD99 expression was also increased in the inflamed mucosa
      compared with unaffected control from the same patients. Serum TNF-alpha and IL
      17A levels were increased in active CD or UC patients, and positively correlated
      with CD99 expression in PBMCs (CD: r = .402, p = .009; r = .350, p = .025. UC: r
      = .289, p = .028; r = .322, p = .014). Moreover, CD99 expression in inflamed
      mucosa was correlated with CDAI, SES-CD, Mayo index, and Truelove grading (r =
      .410, p = .012; r = .341, p = .005; r = .366, p = .002; r = .312, p = .011).
      CONCLUSION: CD99 expression is increased in patients with active IBD, and
      positively correlated with disease activity. Therefore, CD99 expression can be
      used as an index to evaluate the activity of IBD.

PMID- 27866428
TI  - Diagnosis and treatment of epilepsy and sleep apnea comorbidity.
AB  - INTRODUCTION: The comorbidity of epilepsy and sleep apnea is not uncommon. The
      diagnosis and treatment of obstructive sleep apneas will improve the prognosis
      and the quality of life in patients with epilepsy. Areas covered: In this paper,
      the authors review the pathological link between sleep apnea and epilepsy and
      systematically analyze the current literature on the diagnosis and treatment of
      obstructive sleep apnea in patients with epilepsy. This review includes studies
      retrieved from the PubMed, Embase and Google Scholar databases. Expert
      commentary: A variety of treatments are available for OSA and epilepsy
      independently but there are no standards or guidelines for how to implement these
      treatments for patients who suffer from both disorders. The authors expect that
      alternative efficient therapies for comorbidity will be explored, which may
      change the current clinical practice for the management of epileptic patients.

PMID- 27866430
TI  - Assessing catastrophic thinking associated with debilitating mental health
      conditions.
AB  - PURPOSE: The present study examined the psychometric properties of the Symptom
      Catastrophizing Scale (SCS). The SCS items were drawn from the Pain
      Catastrophizing Scale but were modified to make them better suited to the context
      of debilitating mental health conditions that are not necessarily associated with
      pain. The number of items was reduced from 13 to 7, and the response scale was
      simplified. METHODS: The SCS was administered to individuals diagnosed with Major
      Depressive Disorder (MDD) (N = 79) or with a chronic musculoskeletal (MSK)
      condition (N = 88). RESULTS: Exploratory factor analyzes revealed single factor
      solutions of the SCS for both the MSK and MDD samples. The internal consistency
      of the SCS was good. The SCS was significantly correlated with measures of pain
      severity, depressive symptom severity and disability in both samples. Individuals
      with MDD scored higher on the SCS than individuals with MSK. The SCS was shown to
      be sensitive to treatment-related reductions in catastrophic thinking.
      CONCLUSIONS: Preliminary analyzes suggest that the SCS is a reliable and valid
      measure of symptom-related catastrophic thinking associated with debilitating
      mental health conditions. Implications for Rehabilitation Although catastrophic
      thinking has been identified as a risk factor for disability, current assessment
      tools are not well suited for individuals with debilitating mental health
      conditions. This paper describes a brief assessment instrument that can be used
      to assess catastrophic thinking in individuals with debilitating mental health
      conditions. The results of this study suggest that targeting catastrophic
      thinking might yield reductions in symptom severity and disability in work
      disabled individuals with major depressive disorder.

PMID- 27866431
TI  - MicroRNA-targeted therapeutics for lung cancer treatment.
AB  - INTRODUCTION: Lung cancer is one of the leading causes of cancer-related
      mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that
      repress the expression of a broad array of target genes. Many efforts have been
      made to therapeutically target miRNAs in cancer treatments using miRNA mimics and
      miRNA antagonists. Areas covered: This article summarizes the recent findings
      with the role of miRNAs in lung cancer, and discusses the potential and
      challenges of developing miRNA-targeted therapeutics in this dreadful disease.
      Expert opinion: The development of miRNA-targeted therapeutics has become an
      important anti-cancer strategy. Results from both preclinical and clinical trials
      of microRNA replacement therapy have shown some promise in cancer treatment.
      However, some obstacles, including drug delivery, specificity, off-target effect,
      toxicity mediation, immunological activation and dosage determination should be
      addressed. Several delivery strategies have been employed, including naked
      oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors.
      However, delivery remains a main challenge in miRNA-targeting therapeutics.
      Furthermore, immune-related serious adverse events are also a concern, which
      indicates the complexity of miRNA-based therapy in clinical settings.

PMID- 27866432
TI  - Maternal cardiac haemodynamics in severe pre-eclampsia complicated by acute
      pulmonary oedema: A review.
AB  - AIM: To establish alterations in maternal cardiac haemodynamics and function
      using electrocardiography and echocardiography in severe pre-eclampsia
      complicated by acute pulmonary oedema. METHODS: An extensive literature search
      including any research articles, randomised control trials, observational study,
      case report or expert or consensus statement pertaining to severe pre-eclampsia,
      eclampsia, hypertensive crises of pregnancy, pulmonary oedema, maternal cardiac
      haemodynamics, Holter monitoring and maternal echocardiography was done.
      Electronic search strategies included searching the MEDLINE, EMBASE, Cochrane
      Library and Pubmed databases. RESULTS: Toxic substrates from a chronically
      ischaemic placenta and elevated maternal cathecolamines leads to widespread
      elevated systemic vascular resistance, endothelial cell damage and increased left
      ventricular afterload all of which combine to result in left ventricular
      hypertrophy with impaired ventricular filling reflected as significant diastolic
      dysfunction, increased left ventricular end systolic and end diastolic volumes,
      increased left ventricular stroke work, myocardial ischaemia and resultant
      ventricular arrhythmias, in particular ventricular tachycardia. These factors
      could lead to cardiac failure in severe pre-eclampsia, either in combination or
      in independently of each other depending on the magnitude of the angiogenic
      imbalances, degree of elevated systemic vascular resistance, degree of impaired
      myocardial relaxation and diastolic filling anomalies, gene-environment
      interaction and degree of possible pre-existing or potential cardiovascular
      dysfunction. CONCLUSION: Comprehensive maternal echocardiographic and
      electocardiographic assessment should be incorporated in the work-up of severe
      pre-eclampsia to stratify these cases, to enable clinicians to choose the
      appropriate acute hypertensive drug therapy and plan optimal management pathways.

PMID- 27866435
TI  - Wards are carrying out dangerous practices.

PMID- 27866433
TI  - Rasch validation of the Arabic version of the lower extremity functional scale.
AB  - PURPOSE: The purpose of this study was to examine the internal construct validity
      of the Arabic version of the Lower Extremity Functional Scale (20-item Arabic
      LEFS) using Rasch analysis. METHODS: Patients (n = 170) with lower extremity
      musculoskeletal dysfunction were recruited. Rasch analysis of 20-item Arabic LEFS
      was performed. Once the initial Rasch analysis indicated that the 20-item Arabic
      LEFS did not fit the Rasch model, follow-up analyses were conducted to improve
      the fit of the scale to the Rasch measurement model. These modifications included
      removing misfitting individuals, changing item scoring structure, removing
      misfitting items, addressing bias caused by response dependency between items and
      differential item functioning (DIF). RESULTS: Initial analysis indicated
      deviation of the 20-item Arabic LEFS from the Rasch model. Disordered thresholds
      in eight items and response dependency between six items were detected with the
      scale as a whole did not meet the requirement of unidimensionality. Refinements
      led to a 15-item Arabic LEFS that demonstrated excellent internal consistency
      (person separation index [PSI] = 0.92) and satisfied all the requirement of the
      Rasch model. CONCLUSION: Rasch analysis did not support the 20-item Arabic LEFS
      as a unidimensional measure of lower extremity function. The refined 15-item
      Arabic LEFS met all the requirement of the Rasch model and hence is a valid
      objective measure of lower extremity function. The Rasch-validated 15-item Arabic
      LEFS needs to be further tested in an independent sample to confirm its fit to
      the Rasch measurement model. Implications for Rehabilitation The validity of the
      20-item Arabic Lower Extremity Functional Scale to measure lower extremity
      function is not supported. The 15-item Arabic version of the LEFS is a valid
      measure of lower extremity function and can be used to quantify lower extremity
      function in patients with lower extremity musculoskeletal disorders.

PMID- 27866446
TI  - Clinical and serological one-year follow-up of patients after the bite of Ixodes
      ricinus ticks infected with Borrelia burgdorferi sensu lato.
AB  - BACKGROUND: The risk of developing Lyme borreliosis (LB) after the bite of a
      Borrelia (B.) burgdorferi sensu lato (s.l.) infected tick in Romania is unknown.
      METHODS: The present prospective study, performed in 2010-2011 in a hospital in
      Romania, has followed-up clinical and serological outcome of patients that
      presented with B. burgdorferi positive Ixodes (I.) ricinus bite. A second group
      of patients, including age, sex and residence-matched individuals bitten by B.
      burgdorferi negative ticks, was followed-up as a control group. The subjects'
      outcome was evaluated one year after the tick bite. RESULTS: Forty-three out of
      389 ticks detached from patients were positive by hbb Real-Time PCR (RT-PCR) for
      B. burgdorferi s.l. (mainly B. afzelii, but also B. garinii, B. burgdorferi sensu
      stricto, B. spielmanii/B. valaisiana and B. lusitaniae). Twenty patients bitten
      by B. burgdorferi positive ticks and twenty matched control patients returned for
      the one year follow-up. Two patients from the B. burgdorferi positive group
      developed clinical manifestations of acute LB (erythema migrans) and 5 patients
      seroconverted (two from the B. burgdorferi positive group and three from the B.
      burgdorferi negative group). Borrelia afzelii was identified in ticks collected
      from persons that developed erythema migrans (EM). Comparing the two groups of
      patients, no statistical significant differences were found regarding presence of
      clinical symptoms or seroconversion. CONCLUSIONS: No outcome differences were
      found between the group of patients bitten by B. burgdorferi positive ticks and
      the group of patients bitten by B. burgdorferi negative ticks.

PMID- 27866447
TI  - Challenges in congenital central hypoventilation syndrome (Ondine's curse) on
      pregnancy: a case report.

PMID- 27866448
TI  - Dehydration of CO2-alpha-cyclodextrin complex powder by desiccant adsorption
      method and its release properties.
AB  - Stability and release properties of CO2-alpha-cyclodextrin complex powder
      prepared by solid encapsulation (water activity, aw ~ 0.95) followed by moisture
      removal using silica gel and CaCl2 desiccants during post-dehydration were
      investigated. The results showed that CaCl2 reduced aw much faster than silica
      gel did under the same conditions. After approximately 60 h, aw of complex
      powders reduced using silica gel was almost constant at 0.247 (+/-0.012), while
      those treated with CaCl2, aw was 0.225 (+/-0.005) and had not yet reached their
      lowest value. Moisture adsorption by silica gel and CaCl2 also led to a decrease
      in the CO2 concentration of complex powder (higher decrease for silica gel
      adsorption) without affecting the structure and morphology of complex powder. The
      CO2 release properties of CaCl2-aw-reduced complex powder at different relative
      humidities (32.73, 52.86, 75.32 and 97.30% RH), liquid environments (water and
      oil) and packaging methods (normal and vacuum) were also studied.

PMID- 27866449
TI  - Effect of magnesium sulfate on morphine activity retention to control pain after
      herniorrhaphy.
AB  - AIM: This research was carried out to compare magnesium sulfate (MgSO4) with
      isotonic saline in terms of pain control after herniorrhaphy. PATIENTS & METHODS:
      A randomized double-blind study, in which the patients were blind to all. A total
      of 100 patients who were candidates of herniorrhaphy were randomized into two
      groups: experimental and control (50 patients in each). Anesthesia was induced
      with 20% of 4 cc of morphine. The experimental and control group received
      postoperative 20% of 2 cc MgSO4 in 2 cc of isotonic saline and 4 cc of isotonic
      saline, respectively. RESULT: The administration of postoperative morphine in
      control group 0.79 +/- 1.48 mg was significantly higher to the experimental group
      0.17 +/- 0.63 mg during the first 24 h (p = 0.01). CONCLUSION: MgSO4 increased
      the potency of morphine thereby reducing the amount of postoperative pain killer
      needed.

PMID- 27866450
TI  - Recognizing healthcare-associated Staphylococcus aureus bloodstream infections in
      children.

PMID- 27866451
TI  - Health advocacy.
AB  - In the medical profession, activities related to ensuring access to care,
      navigating the system, mobilizing resources, addressing health inequities,
      influencing health policy and creating system change are known as health
      advocacy. Foundational concepts in health advocacy include social determinants of
      health and health inequities. The social determinants of health (i.e. the
      conditions in which people live and work) account for a significant proportion of
      an individual's and a population's health outcomes. Health inequities are
      disparities in health between populations, perpetuated by economic, social, and
      political forces. Although it is clear that efforts to improve the health of an
      individual or population must consider "upstream" factors, how this is
      operationalized in medicine and medical education is controversial. There is a
      lack of clarity around how health advocacy is delineated, how physicians' scope
      of responsibility is defined and how teaching and assessment is conceptualized
      and enacted. Numerous curricular interventions have been described in the
      literature; however, regardless of the success of isolated interventions,
      understanding health advocacy instruction, assessment and evaluation will require
      a broader examination of processes, practices and values throughout medicine and
      medical education. To support the instruction, assessment and evaluation of
      health advocacy, a novel framework for health advocacy is introduced. This
      framework was developed for several purposes: defining and delineating different
      types and approaches to advocacy, generating a "roadmap" of possible advocacy
      activities, establishing shared language and meaning to support communication and
      collaboration across disciplines and providing a tool for the assessment of
      learners and for the evaluation of teaching and programs. Current approaches to
      teaching and assessment of health advocacy are outlined, as well as suggestions
      for future directions and considerations.

PMID- 27866452
TI  - Efficacy of debridement, antibiotic therapy and implant retention within three
      months during postoperative instrumented spine infections.
AB  - BACKGROUND: Postoperative instrumented spine infection (PISI) is a severe
      complication of invasive spine procedures. METHODS: Retrospective study of
      patients treated for PISI between 1st January 2008 and 31st December 2012 in a
      French University Hospital. The objectives of this study were to describe the
      outcome of patients treated with debridement-irrigation, antibiotic therapy and
      implant retention (DAIR) within three months after the occurrence of PISI and to
      identify factors associated with relapse. RESULTS: Among 4290 patients who
      underwent spinal arthrodesis surgery during the 5-year study period, 129 had PISI
      treated by debridement-irrigation in the first three months (3.0%, 95% confidence
      interval [95%CI]: 2.5-3.5). Fifty-two (40%) were female and the median age was 57
      years. Fourteen patients (10.8%) had diabetes and 73 (56.6%) had a BMI (Body Mass
      Index) >=25 kg/m2. Staphylocccus aureus, enterobacteria or polymicrobial
      infections were identified in 44.0, 18.0 and 13.0% of cases, respectively. One
      hundred and six patients (82.2%) and one hundred and twenty-one patients (93.8%)
      were cured after one DAIR and after two DAIR, respectively. In multivariate
      logistic analysis, polymicrobial infection was associated with relapse (Odd Ratio
      [OR] = 3.81; 95%CI: 1.06-13.66; p = .03), while a BMI >=25 kg/m2 was a protective
      factor (OR =0.25; 95%CI: 0.07-0.89; p = .03). CONCLUSION: DAIR may be effective
      for PISI when performed within the first 3 months after onset of infection.
      Relapses are significantly associated with polymicrobial infection and negatively
      associated with moderate overweight. These results need to be confirmed in future
      prospective studies.

PMID- 27866453
TI  - Very rare cause of hemoperitoneum: Ovarian fibroma.

PMID- 27866454
TI  - The role of thymidylate synthase in non-small cell lung cancer treated with
      pemetrexed continuation maintenance therapy.
AB  - Pemetrexed continuation maintenance therapy has been proven to be beneficial for
      patients with advanced non-squamous non-small cell lung cancer (NSCLC). However,
      the eligibility criteria for maintenance treatment are too simple. This study
      sought to evaluate thymidylate synthase (TS) as a predicting biomarker for
      pemetrexed continuation maintenance treatment in NSCLC. Specimens were collected
      from 87 patients treated with pemetrexed continuation maintenance therapy before
      and after four-cycle induction chemotherapy. Real-time quantitative PCR was used
      to detect TS expression in tissues. The TS expression level was correlated with
      characteristic clinical data, radiographic response, progression-free time (PFS)
      and overall survival (OS). Low total TS expression (<8.47) was associated with
      improved PFS (median: 4.7 months vs. 3.5 months, p = 0.034) and improved OS (time
      from random assignment: 16.4 months vs. 11.7 months, p = 0.026; time from
      induction: 19.7 months vs. 14.8 months, p = 0.022). Our results indicate that in
      NSCLC patients treated with pemetrexed continuation maintenance therapy, low TS
      expression is associated with improved PFS and OS.

PMID- 27866455
TI  - Changes in pulsatility and resistance indices of cerebral arteriovenous
      malformation feeder arteries after embolization and surgery.
AB  - OBJECTIVES: Embolization reduces flow in cerebral arteriovenous malformations
      (AVMs) before surgical resection, but changes in pulsatility and resistance
      indices (PI, RI) are unknown. Here, we measure PI, RI in AVM arterial feeders
      before and after embolization/surgery. METHODS: Records of patients who underwent
      AVM embolization and surgical resection at our institution between 2007 and 2014
      and had PI, RI, and flows obtained using quantitative magnetic resonance
      angiography were retrospectively reviewed. PI = [(systolic - diastolic flow
      velocity)/mean flow velocity] and RI = [(systolic - diastolic flow
      velocity)/systolic flow velocity]. Hemodynamic parameters were compared between
      the feeder and contralateral artery before and after embolization/surgery.
      RESULTS: 38 patients were included (6 embolization only, 24 embolization and
      surgery, 8 surgery only). After embolization, flow volume rates within feeders
      decreased significantly (p < 0.001) to match flows in their contralateral
      counterparts (p = 0.78). On the other hand, mean, systolic, and diastolic flow
      velocities (p = 0.60, 0.32, 0.34, respectively) as well as PI, RI (p = 0.99,
      0.68) did not change significantly after embolization. However, after surgery
      mean, systolic, and diastolic flow velocities within feeders decreased
      significantly (p = 0.001, 0.002, 0.001, respectively) and PI, RI normalized to
      match the indices of their contralateral counterparts (p = 0.46, 0.46).
      CONCLUSION: Following partial AVM embolization, PI, RI are unchanged and flow
      velocities in feeder arteries also remain unchanged likely due to redistribution
      of flow through residual nidus. Thus, staged management of AVMs is unlikely to
      increase outflow resistance and offers a safe treatment strategy.

PMID- 27866457
TI  - Motivation in medical education.
AB  - Motivation is a concept which has fascinated researchers for many decades. The
      field of medical education has become interested in motivation recently, having
      always assumed that medical students must be motivated because of their
      commitment to highly specific training, leading to a very specific profession.
      However, motivation is a major determinant of the quality of learning and
      success, the lack of which may well explain why teachers sometimes observe
      medical students who are discouraged, have lost interest or abandon their
      studies, with a feeling of powerlessness or resignation. After describing the
      importance of motivation for learning in medicine, this Guide will define the
      concept of motivation, setting it within the context of a social cognitive
      approach. In the second part of this Guide, recommendations are made, based upon
      the so-called "motivational dynamic model", which provides a multitude of various
      strategies with positive effects on students' motivation to learn.

PMID- 27866456
TI  - Comparison of Saudi Arabian hemodialysis and peritoneal dialysis patients'
      illness perceptions.
AB  - The clinical outcome of patients with end-stage renal disease (ESRD) may differ
      according to their beliefs concerning their illness and its treatment. Both the
      disease itself and negative perceptions of the illness may increase patients'
      morbidity and mortality. This study aims to compare hemodialysis (HD) and
      peritoneal dialysis (PD) patients' illness perceptions and their related factors.
      This cross-sectional comparative study was conducted in five dialysis centers.
      After excluding patients with psychiatric comorbidities, 342 stable dialysis
      patients (HD, n = 267; PD, n = 75) completed a demographic questionnaire and the
      Revised Illness Perception Questionnaire (IPQ-R). The data were analyzed using t
      tests and ANOVAs. Out of the 342 patients, 53.8% were male and 46.2% were female.
      Their mean age was 46.1 +/- 16.5 years. Compared to the HD patients, the PD
      patients perceived their illness to be significantly less chronic (p = .029) and
      more controllable, whether through personal or treatment control (p = .012, p =
      .017). Patients' most common cause of attributions were stress, worry, or poor
      past medical care. PD showed an advantage over HD in terms of perceptions of ESRD
      chronicity and controllability. Intervention programs targeting illness
      perception are needed to support dialysis patients.

PMID- 27866458
TI  - A virilising primary mucinous carcinoid tumour of the ovary in a postmenopausal
      woman: A diagnostic challenge!

PMID- 27866459
TI  - Appearance of external genital organs and types of hymen in Turkish female foetal
      cadavers.
AB  - The present study's purpose was to determine the size and morphometric
      development of the female external genital organs on foetal cadavers. Dimensions
      of labia majora, labia minora and clitoris, bilabial diameter, vertical and
      horizontal diameters of hymenal opening, distance between the external urethral
      orifice and hymenal opening, distance between the clitoris and external urethral
      orifice and anogenital distance were measured. The hymenal types were determined.
      Mean values of parameters according to gestational weeks, months and trimesters
      were calculated. Imperforate hymen were determined in the first trimester. Twenty
      eight foetuses with annular hymen, 25 foetuses with imperforate hymen, and 1
      foetus with septated hymen were determined in the second trimester. Twenty-four
      foetuses with annular hymen, 3 foetuses with imperforate hymen, 1 foetus with
      fimbriated hymen, and 1 foetus with hymenal tag were determined in the third
      trimester. All foetuses in the full term were determined with annular hymen.

PMID- 27866461
TI  - Metabolism, excretion and pharmacokinetics of [14C]glasdegib (PF-04449913) in
      healthy volunteers following oral administration.
AB  - 1. The metabolism, excretion and pharmacokinetics of glasdegib (PF-04449913) were
      investigated following administration of a single oral dose of 100 mg/100 MUCi
      [14C]glasdegib to six healthy male volunteers (NCT02110342). 2. The peak
      concentrations of glasdegib (890.3 ng/mL) and total radioactivity (1043 ngEq/mL)
      occurred in plasma at 0.75 hours post-dose. The AUCinf were 8469 ng.h/mL and
      12,230 ngEq.h/mL respectively, for glasdegib and total radioactivity. 3. Mean
      recovery of [14C]glasdegib-related radioactivity in excreta was 91% of the
      administered dose (49% in urine and 42% in feces). Glasdegib was the major
      circulating component accounting for 69% of the total radioactivity in plasma. An
      N-desmethyl metabolite and an N-glucuronide metabolite of glasdegib represented
      8% and 7% of the circulating radioactivity, respectively. Glasdegib was the major
      excreted component in urine and feces, accounting for 17% and 20% of administered
      dose in the 0-120 hour pooled samples, respectively. Other metabolites with
      abundance <3% of the total circulating radioactivity or dose in plasma or excreta
      were hydroxyl metabolites, a desaturation metabolite, N-oxidation and O
      glucuronide metabolites. 4. Elimination of [14C]glasdegib-derived radioactivity
      was essentially complete, with similar contribution from urinary and fecal
      routes. Oxidative metabolism appears to play a significant role in the
      biotransformation of glasdegib.

PMID- 27866460
TI  - Morphine enhances renal cell carcinoma aggressiveness through promotes survivin
      level.
AB  - BACKGROUND: Morphine is an opioid analgesic drug often used for pain relief in
      cancer patients. However, there is growing evidence that morphine may modulate
      tumor growth, progression and metastasis. Unfortunately, the results obtained by
      these studies are still contradictory. METHODS: In this study, we investigated
      the effect of morphine in human clear cell renal cell carcinoma 786-O, RLC-310
      cells and whether morphine affects on tumor growth in human clear cell renal cell
      carcinoma 786-O, RLC-310 cells. The cell proliferation was determined by MTT
      assay, cell proliferation, migration and invasion assays. Immunofluorescence
      staining and Q-PCR was used to determine the Survivin expression. RESULTS: It was
      shown that morphine enhances proliferation of 786-O, RLC-310 cells, whereas
      morphine promoted the growth and aggressive phenotype of 786-O and RLC-310 cells
      in vitro though Survivin-dependent signaling. CONCLUSIONS: Our data showed that
      morphine promotes RCC growth and increases RCC progression via over-expression of
      Survivin.

PMID- 27866462
TI  - Prolactinoma and pregnancy - a series of cases including pituitary apoplexy.
AB  - The objective of this article is to evaluate the impact of pregnancy in women
      with prolactinoma, the possible consequences of therapy
      maintenance/discontinuation during pregnancy and to assess the type of delivery
      and maternal-foetal obstetrical outcome. A retrospective study of all pregnant
      women with prolactinoma in our Centre between 2006 and 2014 was made. We had 35
      cases of pregnant women with prolactinoma, two of which had an episode of
      pituitary apoplexy during the second trimester. At the time of conception, most
      women were being treated with 5 mg bromocriptine. The majority of women had
      suspended medication in the 8th week of gestation. Caesarean rate was 48.6%. The
      maternal foetal outcome was favourable in all cases.

PMID- 27866465
TI  - Polyphenol-Rich Foods Alleviate Pain and Ameliorate Quality of Life in
      Fibromyalgic Women.
AB  - OBJECTIVES: The present study aimed to describe the antioxidant dietary intake of
      patients with fibromyalgia and explore the association of the results with
      glutathione status, pain, quality of life, and socioeconomic status. METHODS: 38
      fibromyalgic female patients and 35 female controls (mean age = 48.6 +/- 8.1 and
      47.6 +/- 10.0 years, respectively) were evaluated. The number of tender points,
      pain threshold, quality of life, physical activity, socioeconomic status,
      nutritional status, intake of antioxidant micronutrients and foods with high
      total antioxidant capacity, and total salivary glutathione were evaluated.
      RESULTS: The number of tender points, pain threshold, and quality of life were
      worse in the fibromyalgia group. The consumption of vegetable juices was more
      common among women with fibromyalgia and consumption of red wine and beer were
      more common among healthy women. The adjusted mean intakes of antioxidant
      vitamins as well as selenium were higher for the control group (p <= 0.01). There
      was no difference for salivary levels of glutathione between the groups and no
      correlation for intake of antioxidant micronutrients and pain or quality of life
      among fibromyalgic women. However, intake of foods rich in polyphenols was
      associated with lower numbers of tender points (coffee, r = - 0.346; pear, r = -
      0.331) and better quality of life (red fruits, r = - 0.342; dark chocolate, r = -
      0.404) in the fibromyalgic group. In these women, associations between
      glutathione levels and food intake, pain or quality of life were not found.
      CONCLUSION: This study indicated that antioxidant protection from bioactive
      compounds present in fruit and vegetables could have an adjuvant role in
      fibromyalgia treatment.

PMID- 27866463
TI  - Pharmacokinetics, distribution, and disposition of esaxerenone, a novel, highly
      potent and selective non-steroidal mineralocorticoid receptor antagonist, in rats
      and monkeys.
AB  - 1. Esaxerenone (CS-3150) is a novel non-steroidal mineralocorticoid receptor
      antagonist. The pharmacokinetics, tissue distribution, excretion, and metabolism
      of esaxerenone were evaluated in rats and monkeys. 2. Following intravenous
      dosing of esaxerenone at 0.1-3 mg/kg, the total body clearance and the volume of
      distribution were 3.53-6.69 mL/min/kg and 1.47-2.49 L/kg, respectively, in rats,
      and 2.79-3.69 mL/min/kg and 1.34-1.54 L/kg, respectively, in monkeys. The
      absolute oral bioavailability was 61.0-127% in rats and 63.7-73.8% in monkeys. 3.
      After oral administration of [14C]esaxerenone, the radioactivity was distributed
      widely to tissues, with the exception of a low distribution to the central
      nervous system. Both in rats and in monkeys, following oral administration of
      [14C]esaxerenone the main excretion route of the radioactivity was feces. 4. Five
      initial metabolic pathways in rats and monkeys were proposed to be N
      dealkylation, carboxylation, hydroxymethylation, O-glucuronidation, and O
      sulfation. The oxidized metabolism was predominant in rats, while both oxidation
      and glucuronidation were predominant in monkeys.

PMID- 27866464
TI  - Endometriotic cyst fluid induces reactive oxygen species (ROS) in human
      immortalized epithelial cells derived from ovarian endometrioma.
AB  - OBJECTIVES: Endometriotic cyst fluid (ECF) contains a large amount of reactive
      oxygen species (ROS), and endometriotic cysts are exposed to strong oxidative
      stress, which may cause malignant transformation. In this study, ROS production
      by ECF was clinically analysed. METHODS: Human immortalized epithelial cells
      derived from ovarian endometrioma (EMosis-CC/TERT 1) were treated with ECF. In
      addition, ROS production in EMosis-CC/TERT 1 was measured, and its clinical
      significance was analysed. RESULTS: A total of 38 ECF samples were obtained from
      patients diagnosed with endometriotic cysts. In EMosis-CC/TERT1, significantly
      higher levels of ROS were induced by ECF than by the vehicle control and ferric
      nitrilotriacetate. There were no significant differences in ROS production by
      laterality and preoperative serum CA125 values. There were several patients whose
      cyst sizes were approximately 5 cm and had relatively high ROS production.
      Production of ROS by ECF was relatively higher in patients older than 40 years of
      age than in those younger than 40. DISCUSSION: Our study revealed that ROS are
      highly produced by ECF in EMosis-CC/TERT1 cells; therefore, exposure to ECF
      induced strong oxidative stress. Development of a therapeutic strategy to reduce
      ROS production might be useful for preventing malignant transformation of
      endometriotic cysts.

PMID- 27866466
TI  - Preventive Effect of Carvacrol Against Oxidative Damage in Aged Rat Liver.
AB  - The present study was designed to investigate the changes in activities of
      antioxidant enzymes and lipid peroxidation level in the liver of 2, 10 and 20
      months old rats, and to see whether these changes are restored to those of the
      two month old rats after carvacrol treatment. Male rats of 2, 10, and 20 months
      (n = 10 for each group) were used for all the experiments. The aged rats (10 and
      20 months old) were given carvacrol (15 mg/day per body weight) for 30 days.
      Control animals received an equal volume of vehicle. After the treatment, livers
      were removed for estimation of superoxide dismutase-SOD, glutathione-S
      transferase-GST, catalase-CAT activities and lipid peroxidation level. The
      present findings determined that normal aging was associated with a significant
      decrease in the activities of antioxidant enzymes (SOD; 11.87 +/- 0.6 (2 months
      old) vs 7.56 +/- 0.1 (20 months old); P < 0.001) in liver, as well as an increase
      in lipid peroxidation level (MDA; 0.15 +/- 0.01 (2 months old) vs 0.41 +/- 0.01
      (20 months old); P < 0.001) in aged rats. Also, the results of this study
      indicated that carvacrol treatment increased the activities of the antioxidant
      enzymes in 20 months old animals versus the aged matched control group (SOD; 9.87
      +/- 0.4; P < 0.01). Furthermore, carvacrol decreased lipid peroxidation content
      in 10 and 20 months old animals compared with the aged matched control (MDA; 9.87
      +/- 0.4; P < 0.001). Our data shows that carvacrol could be a candidate to
      inhibit the development of age-induced liver damage through inhibition of
      oxidative stress and also increasing antioxidant defenses.

PMID- 27866467
TI  - Vitamin D2, Ergosterol, and Vitamin B2 Content in Commercially Dried Mushrooms
      Marketed in China and Increased Vitamin D2 Content Following UV-C Irradiation.
AB  - Mushrooms are a great source of vitamin D and vitamin B2; however, the content of
      these vitamins in dried mushrooms has not fully been investigated. Thus, the
      objectives of this study were to determine the contents of vitamin D2,
      ergosterol, and vitamin B2 in commercially dried edible mushrooms in China and to
      investigate the effect of UV-C irradiation on fresh mushrooms. Among the 35
      species of dried mushrooms considered for this study, the average ergosterol
      content was 1.98 mg/g, while the average vitamin D2 content was 16.88 ug/g. The
      average vitamin B2 content in dried mushrooms was 12.68 ug/g. Fresh shaggy ink
      caps and oyster mushrooms, when exposed to UV-C at 254 nm at a dose of 0.25 J/cm2
      for 10, 30, and 60 min, showed significantly (p < 0.05) increased vitamin D2
      content (229.7 and 67.0 ug/g, respectively) as compared to its fresh
      counterparts. The conversion of ergosterol to vitamin D2 induced by UV-C
      irradiation at 0.25 J/cm2 was significant (p < 0.05). In conclusion, dried
      commercial mushrooms have higher contents of ergosterol and vitamin D2 than fresh
      mushrooms. UV-C radiation can be used to increase vitamin D2 content in
      mushrooms.

PMID- 27866468
TI  - Intratubular disinfection with tri-antibiotic and calcium hydroxide pastes.
AB  - OBJECTIVE: The aim of this study was to compare the in vitro intradentinal
      antimicrobial ability of the calcium hydroxide and tri-antibiotic pastes.
      MATERIALS AND METHODS: Standard bovine dentin tubes were sterilized and then
      infected with Enterococcus faecalis by a new contamination protocol of great
      depths of dentin. The specimens were filled with the medications, divided into
      two test-groups: calcium hydroxide (Group 1) and tri-antibiotic (Group 2) pastes.
      After 15 days, the teeth were evaluated by microbiological culture and confocal
      laser scanning microscopy (CLSM) with viability dye assay LIVE/DEAD inside
      dentinal tubules. In experiment of culture, the bacterial collection of the
      dentin fragments was done for counting the colony-forming units. RESULTS: The tri
      antibiotic paste had a slightly greater antimicrobial effect; however, there was
      no statistical difference between the groups. CONCLUSIONS: It was concluded that
      the tri-antibiotic paste and the calcium hydroxide paste exercise the same effect
      on intra-tubular decontamination against E. faecalis. So, due the multiples
      advantages, the calcium hydroxide paste can be the choice for dentinal
      decontamination in regenerative procedures.

PMID- 27866470
TI  - The inevitable colonisation of Singapore by Zika virus.
AB  - Singapore is endemic for Dengue virus, with approximately 10,000 to 20,000 annual
      cases reported in recent years. In 2012, Chikungunya was introduced, although the
      numbers of cases reported is much fewer. The current Zika virus pandemic
      originating in Brazil represents a threat to all regions with Aedes mosquitoes,
      particularly those well connected by travellers. In this respect, it was felt
      inevitable that Singapore would eventually realise its third endemic flavivirus.
      In late August 2016, a primary care practitioner observed a cluster of
      geographically linked patients attending with fever and rash. This resulted in
      the first identification of locally transmitted Zika in Singapore on August 27,
      2016. This prompted a robust response in an attempt to stop further spread, which
      continued for approximately 10 days until a large number of laboratory-confirmed
      cases were found as a result of active case finding. Surprisingly, the strain was
      later identified to be of Asian lineage and distinct from that originating in the
      Americas, prompting speculation over the epidemiology of this under recognised
      virus in Asia.

PMID- 27866469
TI  - The effects of percutaneous transluminal coronary intervention on biomarkers of
      oxidative stress in the erythrocytes of elderly male patients.
AB  - OBJECTIVES: Oxidative stress plays a key role in the pathogenesis of coronary
      artery disease. The aim of this study was to compare the effects of percutaneous
      transluminal coronary angioplasty (PTCA) and elective coronary angiography (EC)
      on erythrocytic antioxidant defense in elderly male patients. METHODS: Twenty
      three stable angina pectoris (SAP) patients undergoing PTCA and 18 patients with
      ischemic symptoms scheduled to undergo diagnostic EC were included in the study.
      The concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) and the
      activities of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and cytosolic
      glutathione peroxidase (GSH-Px) were examined in the erythrocytes before,
      immediately after and 2 weeks following PTCA or EC. RESULTS: The MDA
      concentrations were significantly higher and SOD-1, CAT, and GSH-Px activities
      were significantly lower in the PTCA group than in the EC group at baseline. Two
      weeks after treatment, the activities of the enzymes significantly increased in
      both groups, whereas the MDA concentrations decreased only in the PTCA patients.
      CONCLUSIONS: The results confirm that an advanced state of atherosclerosis is
      related to greater levels of oxidative stress. The study indicates that both
      procedures may induce antioxidant defenses; however, PTCA exclusively induces a
      long-term reduction in lipid peroxidation.

PMID- 27866471
TI  - Distal renal tubular acidosis without renal impairment after use of tenofovir: a
      case report.
AB  - BACKGROUND: Tenofovir, one of antiretroviral medication to treat human
      immunodeficiency virus (HIV) infection, is known to cause proximal renal tubular
      acidosis such as Fanconi syndrome, but cases of distal renal tubular acidosis had
      never been reported. CASE PRESENTATION: A 20-year-old man with HIV infection
      developed nausea and vomiting without diarrhea after starting antiretroviral
      therapy. Arterial blood gas revealed non-anion-gap metabolic acidosis and urine
      test showed positive urine anion gap. Tenofovir, one of antiretroviral medicine
      the patient received, was considered to be the cause of this acidosis and all
      antiretroviral drugs were discontinued. Symptoms disappeared promptly without
      recurrence of symptoms after resuming antiretroviral medications without
      tenofovir. CONCLUSION: Distal renal tubular acidosis caused by tenofovir, without
      renal impairment is very rare. Since causes of nausea and vomiting among HIV/AIDS
      patients are very diverse, awareness of this phenomenon is useful in diagnosing
      and managing the problem.

PMID- 27866472
TI  - Outcomes measures in a decade of dementia and mild cognitive impairment trials.
AB  - BACKGROUND: In a research study, to give a comprehensive evaluation of the impact
      of interventions, the outcome measures should reflect the lived experience of the
      condition. In dementia studies, this necessitates the use of outcome measures
      which capture the range of disease effects, not limited to cognitive functioning.
      In particular, assessing the functional impact of cognitive impairment is
      recommended by regulatory authorities, but there is no consensus on the optimal
      approach for outcome assessment in dementia research. Our aim was to describe the
      outcome measures used in dementia and mild cognitive impairment (MCI)
      intervention studies, with particular interest in those evaluating patient
      centred outcomes of functional performance and quality of life. METHODS: We
      performed a focused review of the literature with multiple embedded checks of
      internal and external validity. We used the Cochrane Dementia and Cognitive
      Improvement Group's register of dementia studies, ALOIS. ALOIS was searched to
      obtain records of all registered dementia and MCI intervention studies over a 10
      year period (2004-2014). We included both published and unpublished materials.
      Outcomes were categorised as cognitive, functional, quality of life, mood,
      behaviour, global/disease severity and institutionalisation. RESULTS: From an
      initial return of 3271 records, we included a total of 805 records, including 676
      dementia trial records and 129 MCI trial records. Of these, 78 % (630) originated
      from peer-reviewed publications and 60 % (487) reported results of
      pharmacological interventions. Cognitive outcomes were reported in 70 % (563), in
      contrast with 29 % (237) reporting measures of functional performance and only 13
      % (102) reporting quality of life measures. We identified significant
      heterogeneity in the tools used to capture these outcomes, with frequent use of
      non-standardised tests. CONCLUSIONS: This focus on cognitive performance
      questions the extent to which intervention studies for dementia are evaluating
      outcome measures which are relevant to individual patients and their carers. The
      heterogeneity in measures, use of bespoke tools and poor descriptions of test
      strategy all support the need for a more standardised approach to the conduct and
      reporting of outcomes assessments.

PMID- 27866473
TI  - Top 100 cited articles in cardiovascular magnetic resonance: a bibliometric
      analysis.
AB  - BACKGROUND: With limited health care resources, bibliometric studies can help
      guide researchers and research funding agencies towards areas where reallocation
      or increase in research activity is warranted. Bibliometric analyses have been
      published in many specialties and sub-specialties but our literature search did
      not reveal a bibliometric analysis on Cardiovascular Magnetic Resonance (CMR).
      The main objective of the study was to identify the trends of the top 100 cited
      articles on CMR research. METHODS: Web of Science (WOS) search was used to create
      a database of all English language scientific journals. This search was then
      cross-referenced with a similar search term query of Scopus(r) to identify
      articles that may have been missed on the initial search. Articles were ranked by
      citation count and screened by two independent reviewers. RESULTS: Citations for
      the top 100 articles ranged from 178 to 1925 with a median of 319.5. Only 17
      articles were cited more than 500 times, and the vast majority (n = 72) were
      cited between 200-499 times. More than half of the articles (n = 52) were from
      the United States of America, and more than one quarter (n = 21) from the United
      Kingdom. More than four fifth (n = 86) of the articles were published between the
      time period 2000-2014 with only 1 article published before 1990. Circulation and
      Journal of the American College of Cardiology made up more than half (n = 62) of
      the list. We found 10 authors who had greater than 5 publications in the list.
      CONCLUSION: Our study provides an insight on the characteristics and quality of
      the most highly cited CMR literature, and a list of the most influential
      references related to CMR.

PMID- 27866475
TI  - An Increase in Healthcare-Associated Clostridium difficile Infection Associated
      with Use of a Defective Peracetic Acid-Based Surface Disinfectant.
AB  - BACKGROUND We investigated an increase in the incidence of healthcare-associated
      Clostridium difficile infection (CDI) that occurred following a change from a
      bleach disinfectant to a peracetic acid-based disinfectant. OBJECTIVE To evaluate
      the efficacy of the peracetic acid-based disinfectant. DESIGN Laboratory-based
      product evaluation. METHODS The commercial peracetic acid-based product is
      activated on site by mixing a small volume of concentrated hydrogen peroxide and
      peracetic acid present in a "SmartCap" reservoir with the remaining contents of
      the container. We measured concentrations of peracetic acid in newly activated
      and in-use product and determined the stability of nonactivated and activated
      product. We tested the efficacy of the product against C. difficile spores using
      the American Society for Testing and Materials standard quantitative carrier disk
      test method. RESULTS Measured concentrations of peracetic acid (50-800 parts per
      million [ppm]) were significantly lower than the level stated on the product
      label (1,500 ppm), and similar results were obtained for containers from multiple
      lot numbers and from another hospital. Product with peracetic acid levels below
      600 ppm had significantly reduced activity against C. difficile spores. Peracetic
      acid concentrations were reduced markedly after storage of either activated or
      nonactivated product for several weeks. The Environmental Protection Agency
      confirmed the finding of low disinfectant levels and ordered discontinuation of
      sale of the product. CONCLUSION Use of a defective peracetic acid-based surface
      disinfectant may have contributed to an increase in healthcare-associated CDI.
      Our findings highlight the importance of evaluating the efficacy of liquid
      disinfectants in healthcare settings. Infect Control Hosp Epidemiol 2017;38:300
      305.

PMID- 27866474
TI  - Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute
      rejection and improving small bowel transplantation outcomes in rats.
AB  - BACKGROUND: We determined whether bone marrow mesenchymal stem cells (BMMSCs)
      transduced with heme oxygenase-1 (HO-1), a cytoprotective and immune-protective
      factor, could improve outcomes for small bowel transplantation (SBTx) in rats.
      METHODS: We performed heterotopic SBTx from Brown Norway rats to Lewis rats,
      before infusing Ad/HO-1-transduced BMMSCs (Ad/HO-1/BMMSCs) through the
      superficial dorsal veins of the penis. Respective infusions with Ad/BMMSCs,
      BMMSCs, and normal saline served as controls. The animals were sacrificed after
      1, 5, 7, or 10 days. At each time point, we measured small bowel histology and
      apoptosis, HO-1 protein and mRNA expression, natural killer (NK) cell activity,
      cytokine concentrations in serum and intestinal graft, and levels of regulatory T
      (Treg) cells. RESULTS: The saline-treated control group showed aggravated acute
      cellular rejection over time, with mucosal destruction, increased apoptosis, NK
      cell activation, and upregulation of proinflammatory and immune-related
      mediators. Both the Ad/BMMSC-treated group and the BMMSC-treated group exhibited
      attenuated acute cellular rejection at an early stage, but the effects receded 7
      days after transplantation. Strikingly, the Ad/HO-1/BMMSC-treated group
      demonstrated significantly attenuated acute cellular rejection, reduced apoptosis
      and NK cell activity, and suppressed concentrations of inflammation and immune
      related cytokines, and upregulated expression of anti-inflammatory cytokine
      mediators and increased Treg cell levels. CONCLUSION: Our data suggest that Ad/HO
      1-transduced BMMSCs have a reinforced effect on reducing acute rejection and
      protecting the outcome of SBTx in rats.

PMID- 27866477
TI  - Cross-reactivity of the 31 kDa antigen of Angiostrongylus cantonensis - Dealing
      with the immunodiagnosis of meningoencephalitis.
AB  - The primary causative agent of eosinophilic meningoencephalitis (EoM) in endemic
      regions is the nematode Angiostrongylus cantonensis. The occurrence of EoM was
      previously restricted to countries in Southeast Asia and the Pacific Islands;
      however, more recently, it has been reported from other regions, including
      Brazil. The commonly used diagnosis is detection of specific antibody reactivity
      to the 31 kDa antigen, which is derived from female worm somatic extracts. Here
      we report the occurrence of cross-reactivity to this antigen in sera from other
      parasitic infections, especially those that may cause EoM, such as
      gnathostomiasis, toxocariasis, hydatidosis and strongyloidiasis. We also
      demonstrated that the cross-reactivity, in part, is dependent of the
      concentration of antigen used in Western blot assays. We discuss the importance
      of these findings on the interpretation of this test.

PMID- 27866479
TI  - Consumption of fruits and vegetables among adolescents: a multi-national
      comparison of eleven countries in the Eastern Mediterranean Region.
AB  - A regional cross-country profile of fruit and vegetable (F&V) consumption is
      lacking in the Eastern Mediterranean Region (EMR). This study examines the
      prevalence of and differences in consumption of F&V >=5 times/d among adolescents
      in eleven EMR countries, and describes differences in the proportions of taking
      F&V >=5 times/d by sex, age and BMI. The study included 26 328 school adolescents
      (13-15 years) with complete data on consumption of F&V, age, sex, weight and
      height taken from the Global School-based Student Health Survey conducted in the
      EMR between 2005 and 2009. Overall, only 19.4 % of adolescents reported consuming
      F&V >=5 times/d. The highest prevalence was reported in Djibouti (40.4 %) and the
      lowest was reported in Pakistan (10.0 %). Statistically significant differences
      in prevalence were observed across countries (P<0.05). With the exception of
      Oman, Libya and Djibouti, significantly more males than females ate F&V >=5
      times/d. The proportion of students consuming F&V >=5 times/d also varied
      significantly in all countries based on BMI (P<0.0001), with students within
      normal BMI having the highest frequency. A negative trend was observed between
      age and intake of F&V >=5 times/d in most of the eleven EMR countries except
      Jordan, Djibouti and Morocco. The prevalence of adequate intake of F&V is low in
      the eleven EMR countries. There is a need for interventions to increase the
      prevalence of adolescents consuming F&V >=5 times/d. Interventions should take
      into consideration the psychosocial, environmental and socio-environmental
      factors influencing F&V intake within countries.

PMID- 27866480
TI  - Consumption of nutritional pellets with Duddingtonia flagrans fungal
      chlamydospores reduces infective nematode larvae of Haemonchus contortus in
      faeces of Saint Croix lambs.
AB  - Two groups of six Haemonchus contortus infected Saint Croix lambs each received
      different diets for 11 weeks: control group, commercial food, molasses and
      lucerne hay; and treated group, nutritional pellets (NPs) containing Duddingtonia
      flagrans at 2 * 106 chlamydospores/kg body weight (BW), sorghum and lucerne hay.
      Mean BW gain (BWG), body condition score (BCS) and packed cell volume (PCV) and
      also eggs/g of faeces (EPG) and recovered L3 were compared using a repeated
      measures across time model. Groups had similar BWG (control 139.7 +/- 0.035 g/day
      and treated 167.7 +/- 0.041 g/day), BCS (control 3.6 +/- 0.39 and treated 3.4 +/-
      0.46) and PCV (control 32.5 +/- 1.68% and treated 30.0 +/- 1.68%). The mean EPG
      of the control group was 1215 +/- 1040 and in the treated group it was 2097.91 +/
      2050. No reduction in larval population was observed during weeks 2 and 3. The
      greatest larval population reduction in the faeces of treated lambs was observed
      during the first week (70.5%) and from weeks 6 to 11, with a mean value close to
      70% (P < 0.05). In general, both experimental groups showed a similar feed
      conversion. It was concluded that both diets resulted in similar lamb growth,
      PCV, BCS and H. contortus EPG. However, NP consumption significantly reduced the
      H. contortus L3 population in lamb faeces.

PMID- 27866481
TI  - Effect of inoculum age and physical parameters on in vitro culture of the
      entomopathogenic nematode Steinernema feltiae.
AB  - Entomopathogenic nematodes (EPNs) of the families Steinernematidae and
      Heterorhabditidae have a symbiotic association with bacteria which makes them
      virulent against insects. EPNs have been mass produced using in vivo and in vitro
      methods, including both solid and liquid fermentation. This study assessed the
      effect of nematode inoculum age on the production of Steinernema feltiae in
      liquid, solid and biphasic processes. Several physical parameters were also
      assessed: the effect of medium viscosity, flask size and aeration speed on the
      recovery and yield of infective juveniles (IJs). Inoculum age treatments included
      inoculum liquid cultures that were 7, 14, 21 and 28 days old. Nematodes from the
      same inoculum were added to one liquid medium (liquid culture), one solid medium
      with bacteria previously grown in sponge (solid culture) and a variation of the
      solid medium (a biphasic culture), in which the bacteria were first grown in
      liquid and, then, soaked into the sponges, with the purpose of providing a more
      homogeneous bacterial culture before nematode inoculation. Experiments were
      conducted in Erlenmeyer flasks. Eight treatments were established involving
      combinations of three variables: two media (with and without 0.2% agar), two
      flask sizes (250 and 150 ml) and two agitation speeds (180 and 280 rpm). The
      study showed increases in nematode yield for liquid cultures, but not for solid
      or biphasic cultures, with the advance of the inoculum age up to 28 days of
      growth. Furthermore, the addition of 0.2% agar to the liquid medium and
      increasing the aeration rate by using larger flasks with higher agitation speed
      may increase nematode recovery and final yield. The experiments were conducted
      using shake flasks but the results may also be applicable for bioreactors.

PMID- 27866478
TI  - Evaluating drug resistance in visceral leishmaniasis: the challenges.
AB  - For decades antimonials were the drugs of choice for the treatment of visceral
      leishmaniasis (VL), but the recent emergence of resistance has made them
      redundant as first-line therapy in the endemic VL region in the Indian
      subcontinent. The application of other drugs has been limited due to adverse
      effects, perceived high cost, need for parenteral administration and increasing
      rate of treatment failures. Liposomal amphotericin B (AmB) and miltefosine (MIL)
      have been positioned as the effective first-line treatments; however, the number
      of monotherapy MIL-failures has increased after a decade of use. Since no
      validated molecular resistance markers are yet available, monitoring and
      surveillance of changes in drug sensitivity and resistance still depends on
      standard phenotypic in vitro promastigote or amastigote susceptibility assays.
      Clinical isolates displaying defined MIL- or AmB-resistance are still fairly
      scarce and fundamental and applied research on resistance mechanisms and dynamics
      remains largely dependent on laboratory-generated drug resistant strains. This
      review addresses the various challenges associated with drug susceptibility and 
      resistance monitoring in VL, with particular emphasis on the choice of strains,
      susceptibility model selection and standardization of procedures with specific
      read-out parameters and well-defined threshold criteria. The latter are essential
      to support surveillance systems and safeguard the limited number of currently
      available antileishmanial drugs.

PMID- 27866476
TI  - The impact of education, country, race and ethnicity on the self-report of
      postpartum depression using the Edinburgh Postnatal Depression Scale.
AB  - BACKGROUND: Universal screening for postpartum depression is recommended in many
      countries. Knowledge of whether the disclosure of depressive symptoms in the
      postpartum period differs across cultures could improve detection and provide new
      insights into the pathogenesis. Moreover, it is a necessary step to evaluate the
      universal use of screening instruments in research and clinical practice. In the
      current study we sought to assess whether the Edinburgh Postnatal Depression
      Scale (EPDS), the most widely used screening tool for postpartum depression,
      measures the same underlying construct across cultural groups in a large
      international dataset. METHOD: Ordinal regression and measurement invariance were
      used to explore the association between culture, operationalized as education,
      ethnicity/race and continent, and endorsement of depressive symptoms using the
      EPDS on 8209 new mothers from Europe and the USA. RESULTS: Education, but not
      ethnicity/race, influenced the reporting of postpartum depression [difference
      between robust comparative fit indexes (?*CFI) 0.01), but not between European
      countries (?*CFI < 0.01). CONCLUSIONS: Investigators and clinicians should be
      aware of the potential differences in expression of phenotype of postpartum
      depression that women of different educational backgrounds may manifest. The
      increasing cultural heterogeneity of societies together with the tendency towards
      globalization requires a culturally sensitive approach to patients, research and
      policies, that takes into account, beyond rhetoric, the context of a person's
      experiences and the context in which the research is conducted.

PMID- 27866483
TI  - Wild and vaccine-derived poliovirus circulation, and implications for polio
      eradication.
AB  - Polio cases due to wild virus are reported by only three countries in the world.
      Poliovirus type 2 has been globally eradicated and the last detection of
      poliovirus type 3 dates to November 2012. Poliovirus type 1 remains the only
      circulating wild strain; between January and September 2016 it caused 26 cases
      (nine in Afghanistan, 14 in Pakistan, three in Nigeria). The use of oral polio
      vaccine (OPV) has been the key to success in the eradication effort. However,
      paradoxically, moving towards global polio eradication, the burden caused by
      vaccine-derived polioviruses (VDPVs) becomes increasingly important. In this
      paper circulation of both wild virus and VDPVs is reviewed and implications for
      the polio eradication endgame are discussed. Between April and May 2016 OPV2
      cessation has been implemented globally, in a coordinated switch from trivalent
      OPV to bivalent OPV. In order to decrease the risk for cVDPV2 re-emergence
      inactivated polio vaccine (IPV) has been introduced in the routine vaccine
      schedule of all countries. The likelihood of re-emergence of cVDPVs should
      markedly decrease with time after OPV cessation, but silent circulation of
      polioviruses cannot be ruled out even a long time after cessation. For this
      reason, immunity levels against polioviruses should be kept as high as possible
      in the population by the use of IPV, and both clinical and environmental
      surveillance should be maintained at a high level.

PMID- 27866482
TI  - Insight as a social identity process in the evolution of psychosocial functioning
      in the early phase of psychosis.
AB  - BACKGROUND: Awareness of illness (insight) has been found to have contradictory
      effects for different functional outcomes after the early course of psychosis.
      Whereas it is related to psychotic symptom reduction and medication adherence, it
      is also associated with increased depressive symptoms. In this line, the specific
      effects of insight on the evolution of functioning over time have not been
      identified, and social indicators, such as socio-occupational functioning have
      barely been considered. Drawing from social identity theory we investigated the
      impact of insight on the development of psychosocial outcomes and the
      interactions of these variables over time. METHOD: The participants, 240 patients
      in early phase of psychosis from the Treatment and Early Intervention in
      Psychosis Program (TIPP) of the University Hospital of Lausanne, Switzerland,
      were assessed at eight time points over 3 years. Cross-lagged panel analyses and
      multilevel analyses were conducted on socio-occupational and general functioning
      [Social and Occupational Functioning Assessment Scale (SOFAS) and Global
      Assessment of Functioning (GAF)] with insight, time and depressive symptoms as
      independent variables. RESULTS: Results from multilevel analyses point to an
      overall positive impact of insight on psychosocial functioning, which increases
      over time. Yet the cross-lagged panel analysis did not reveal a systematic
      positive and causal effect of insight on SOFAS and GAF scores. Depressive
      symptoms seem only to be relevant in the beginning of the treatment process.
      CONCLUSIONS: Our results point to a complex process in which the positive impact
      of insight on psychosocial functioning increases over time, even when considering
      depressive symptoms. Future studies and treatment approaches should consider the
      procedural aspect of insight.

PMID- 27866484
TI  - Exploring DSM-5 ADHD criteria beyond young adulthood: phenomenology, psychometric
      properties and prevalence in a large three-decade birth cohort.
AB  - BACKGROUND: There are still uncertainties on the psychometric validity of the DSM
      5 attention deficit hyperactivity disorder (ADHD) criteria for its use in the
      adult population. We aim to describe the adult ADHD phenotype, to test the
      psychometric properties of the DSM-5 ADHD criteria, and to calculate the
      resulting prevalence in a population-based sample in their thirties. METHOD: A
      cross-sectional evaluation using the DSM-5 ADHD criteria was carried out in 3574
      individuals from the 1982 Pelotas Birth Cohort. Through receiver operator curve,
      latent and regression analyses, we obtained parameters on construct and
      discriminant validity. Still, prevalence rates were calculated for different sets
      of criteria. RESULTS: The latent analysis suggested that the adult ADHD phenotype
      is constituted mainly by inattentive symptoms. Also, inattention symptoms were
      the symptoms most associated with impairment. The best cut-off for diagnosis was
      four symptoms, but sensitivity and specificity for this cut-off was low. ADHD
      prevalence rates were 2.1% for DSM-5 ADHD criteria and 5.8% for ADHD disregarding
      age-of-onset criterion. CONCLUSIONS: The bi-dimensional ADHD structure proposed
      by the DSM demonstrated both construct and discriminant validity problems when
      used in the adult population, since inattention is a much more relevant feature
      in the adult phenotype. The use of the DSM-5 criteria results in a higher
      prevalence of ADHD when compared to those obtained by DSM-IV, and prevalence
      would increase almost threefold when considering current ADHD syndrome. These
      findings suggest a need for further refinement of the criteria for its use in the
      adult population.

PMID- 27866485
TI  - Determinants of the nurses' and nursing assistants' request for antipsychotics
      for people with dementia.
AB  - BACKGROUND: Although physicians are responsible for writing the antipsychotic
      prescriptions for patients with dementia, the initiative is often taken by nurses
      or nursing assistants. To reduce antipsychotics uses, one needs to understand the
      reasons for nurses and nursing assistants to request them. This study gives an
      overview of the influencing factors for this request based on the Theory of
      Planned Behavior in which attitude, beliefs, and behavioral control is thought to
      influence the intention to request, which in turn affects the behavior to request
      for a prescription. METHODS: Eighty-one nurses and nursing assistants of one
      Dutch nursing home organization completed an online survey. RESULTS: Nurses and
      nursing assistants frequently agreed on items related to the positive effects of
      antipsychotics for the resident and for the staff. Nurses and nursing assistants
      with a lower job satisfaction were more likely to call for antipsychotics. Having
      more positive beliefs about treatment effects and feel of being more in control
      toward asking for antipsychotics were positively associated with intention to
      call. All variables explained 59% of the variance of intention. The current
      position (nurse/nursing assistant) was associated with actual behavior to call.
      The explained variance was 25%. CONCLUSIONS: Policy-makers should focus on the
      nurses' and nursing assistants' belief in positive effects of antipsychotics for
      the resident, which is not in line with available evidence. Nurses and nursing
      assistants should be educated about the limited effectiveness of antipsychotics.

PMID- 27866487
TI  - Tuberculosis infection testing in HIV-positive men who have sex with men from
      Xi'an China.
AB  - In individuals with latent tuberculosis (TB) infection, those living with human
      immunodeficiency virus (HIV) had a 20-37 times higher risk of developing active
      TB compared to those without HIV infection. Systematic testing and treatment of
      latent TB infection are priorities in HIV-infected persons. In China, the
      prevalence of HIV infection in men who have sex with men (MSM) has gradually
      increased in the past decade. However, the prevalence of TB infection has been
      studied sparsely in HIV-infected MSM. Hence, we conducted a pilot study in MSM
      living with HIV infection in Xi'an city to evaluate TB infection status by means
      of interferon-gamma release assay (IGRA). A total of 182 HIV-infected MSM were
      included in this study, the prevalence of IGRA positivity was observed to be
      8.79% (16/182). IGRA quantitative results were not statistically influenced by
      the CD4 cell counts of the study participants. However, IGRA positivity was found
      to be lower than our previously reported data from the general population. This
      suggests that immunological deficiency might decrease the sensitivity of IGRA and
      thus increase the number of false negatives. Our primary results, suggesting
      systematic testing and treatment of latent TB infection together with active case
      finding, were equally important for TB control in persons living with HIV
      infection.

PMID- 27866486
TI  - The effects of cannabis use on salience attribution: a systematic review.
AB  - OBJECTIVE: The relationship between cannabis use and the onset of psychosis is
      well established. Aberrant salience processing is widely thought to underpin many
      of these symptoms. Literature explicitly investigating the relationship between
      aberrant salience processing and cannabis use is scarce; with those few studies
      finding that acute tetrahydrocannabinol (THC) administration (the main
      psychoactive component of cannabis) can result in abnormal salience processing in
      healthy cohorts, mirroring that observed in psychosis. Nevertheless, the extent
      of and mechanisms through which cannabis has a modulatory effect on aberrant
      salience, following both acute and chronic use, remain unclear. METHODS: Here, we
      systematically review recent findings on the effects of cannabis use - either
      through acute THC administration or in chronic users - on brain regions
      associated with salience processing (through functional MRI data); and
      performance in cognitive tasks that could be used as either direct or indirect
      measures of salience processing. We identified 13 studies either directly or
      indirectly exploring salience processing. Three types of salience were identified
      and discussed - incentive/motivational, emotional/affective, and attentional
      salience. RESULTS: The results demonstrated an impairment of immediate salience
      processing, following acute THC administration. Amongst the long-term cannabis
      users, normal salience performance appeared to be underpinned by abnormal neural
      processes. CONCLUSIONS: Overall, the lack of research specifically exploring the
      effects of cannabis use on salience processing, weaken any conclusions drawn.
      Additional research explicitly focussed on salience processing and cannabis use
      is required to advance our understanding of the neurocognitive mechanisms
      underlying the association between cannabis use and development of psychosis.

PMID- 27866488
TI  - Disposable Bronchoscope Model for Simulating Endoscopic Reprocessing and
      Surveillance Cultures.
AB  - BACKGROUND Endoscope-associated infections are reported despite following proper
      reprocessing methods. Microbiological testing can confirm the adequacy of
      endoscope reprocessing. Multiple controversies related to the method and
      interpretation of microbiological testing cultures have arisen that make their
      routine performance a complex target. OBJECTIVE We conducted a pilot study using
      disposable bronchoscopes (DBs) to simulate different reprocessing times and
      soaking times and to compare high-level disinfection versus ethylene oxide
      sterilization. We also reviewed the time to reprocessing and duration of the
      procedures. METHODS Bronchoscopes were chosen because an alternative disposable
      scope is commercially available and because bronchoscopes are more prone to
      delays in processing. Disposable bronchoscopes were contaminated using a liquid
      bacterial suspension and were then incubated for 1-4 hours. Standard processing
      and high-level disinfection were performed on 36 endoscopes. Ethylene oxide
      sterilization was performed on 21 endoscopes. Endoscope cultures were performed
      using the standard "brush, flush, brush" technique. RESULTS After brushing was
      performed, a final water-flush culture procedure was the most effective method of
      detecting bacterial persistence on the disposable scopes. Klebsiella pneumoniae
      was the most commonly recovered organism after reprocessing. Ethylene oxide
      sterilization did not result in total elimination of viable bacteria. CONCLUSION
      Routine endoscopy cultures may be required to assess the adequacy of endoscopic
      processing. Infect Control Hosp Epidemiol 2017;38:136-142.

PMID- 27866489
TI  - Exploring genotype concordance in epidemiologically linked cases of tuberculosis
      in New York City.
AB  - Comparing genotype results of tuberculosis (TB) isolates from individuals
      diagnosed with TB can support or refute transmission; however, these conclusions
      are based upon the criteria used to define a genotype match. We used a genotype
      match definition which allowed for variation in IS6110 restriction fragment
      length polymorphism (RFLP) to support transmission between epidemiologically
      linked persons. Contacts of individuals with infectious TB (index cases)
      diagnosed in New York City from 1997 to 2003 who subsequently developed TB
      (contact cases) from 1997 to 2007 were identified. For each contact case and
      index case (case-pair), isolate genotypes (spoligotype and RFLP results) were
      evaluated. Isolates from case-pairs were classified as exact or non-exact
      genotype match. Genotypes from non-exact match case-pairs were reviewed at the
      genotyping laboratory to determine if the isolates met the near-genotype-match
      criteria (exactly matching spoligotype and similar RFLP banding patterns). Of 118
      case-pairs identified, isolates from 83 (70%) had exactly matching genotypes and
      14 (12%) had nearly matching genotypes (supporting transmission), while the
      remaining 21 (18%) case-pairs had discordant genotypes (refuting transmission).
      Using identical genotype-match criteria for isolates from case-pairs
      epidemiologically linked through contact investigation may lead to
      underestimation of transmission. TB programmes should consider the value of
      expanding genotype-match criteria to more accurately assess transmission between
      such cases.

PMID- 27866491
TI  - Conducting longitudinal, process-oriented research with conflict-affected youth:
      Solving the inevitable challenges.
AB  - The reader might get the impression that the four projects described in this
      Special Section proceeded in a systematic and predictable way. Of course, those
      of us engaged in each research project encountered pitfalls and challenges along
      the way. A main goal of this Special Section is to provide pathways and
      encouragement for those who may be interested in advancing high-quality research
      on this topic. In this paper, we describe a set of practical and ethical
      challenges that we encountered in conducting our longitudinal, process-oriented,
      and translational research with conflict-affected youth, and we illustrate how
      problems can be solved with the goal of maintaining the internal and external
      validity of the research designs. We are hopeful that by describing the
      challenges of our work, and how we overcame them, which are seldom treated in
      this or any other literature on research on child development in high-risk
      contexts, we can offer a realistic and encouraging picture of conducting
      methodologically sound research in conflict-affected contexts.

PMID- 27866490
TI  - MULTILEVEL LINEAR REGRESSION ANALYSIS OF FACTORS INFLUENCING BODY MASS INDEX
      AMONG BANGLADESHI MARRIED NON-PREGNANT WOMEN.
AB  - The aim of this study was to investigate the socioeconomic and demographic
      factors influencing the body mass index (BMI) of non-pregnant married Bangladeshi
      women of reproductive age. Secondary (Hierarchy) data from the 2011 Bangladesh
      Demographic and Health Survey, collected using two-stage stratified cluster
      sampling, were used. Two-level linear regression analysis was performed to remove
      the cluster effect of the variables. The mean BMI of married non-pregnant
      Bangladeshi women was 21.60+/-3.86 kg/m2, and the prevalence of underweight,
      overweight and obesity was 22.8%, 14.9% and 3.2%, respectively. After removing
      the cluster effect, age and age at first marriage were found to be positively
      (p<0.01) related with BMI. Number of children was negatively related with women's
      BMI. Lower BMI was especially found among women from rural areas and poor
      families, with an uneducated husband, with no television at home and who were
      currently breast-feeding. Age, total children ever born, age at first marriage,
      type of residence, education level, level of husband's education, wealth index,
      having a television at home and practising breast-feeding were found to be
      important predictors for the BMI of married Bangladeshi non-pregnant women of
      reproductive age. This information could be used to identify sections of the
      Bangladeshi population that require special attention, and to develop more
      effective strategies to resolve the problem of malnutrition.

PMID- 27866492
TI  - Predictive modelling of Ross River virus notifications in southeastern Australia.
AB  - Ross River virus (RRV) is a mosquito-borne virus endemic to Australia. The
      disease, marked by arthritis, myalgia and rash, has a complex epidemiology
      involving several mosquito species and wildlife reservoirs. Outbreak years
      coincide with climatic conditions conducive to mosquito population growth. We
      developed regression models for human RRV notifications in the Mildura Local
      Government Area, Victoria, Australia with the objective of increasing
      understanding of the relationships in this complex system, providing trigger
      points for intervention and developing a forecast model. Surveillance, climatic,
      environmental and entomological data for the period July 2000-June 2011 were used
      for model training then forecasts were validated for July 2011-June 2015.
      Rainfall and vapour pressure were the key factors for forecasting RRV
      notifications. Validation of models showed they predicted RRV counts with an
      accuracy of 81%. Two major RRV mosquito vectors (Culex annulirostris and Aedes
      camptorhynchus) were important in the final estimation model at proximal lags.
      The findings of this analysis advance understanding of the drivers of RRV in
      temperate climatic zones and the models will inform public health agencies of
      periods of increased risk.

PMID- 27866493
TI  - Dietary DHA and health: cognitive function ageing.
AB  - DHA is a key nutritional n-3 PUFA and needs to be supplied by the human diet. DHA
      is found in significant amounts in the retinal and neuronal cell membranes due to
      its high fluidity. Indeed, DHA is selectively concentrated in the synaptic and
      retinal membranes. DHA is deemed to display anti-inflammatory properties and to
      reduce the risk of CVD. Consumption of larger amounts of DHA appears to reduce
      the risk of depression, bipolar disorder, schizophrenia and mood disorders.
      Conversely, it has been shown that loss of DHA from the nerve cell membrane leads
      to dysfunction of the central nervous system in the form of anxiety,
      irritability, susceptibility to stress, dyslexia, impaired memory and cognitive
      functions, and extended reaction times. DHA plays an important role in ensuring a
      healthy ageing, by thwarting macular degeneration, Alzheimer's disease, and other
      brain disorders at the same time as enhancing memory and strengthening
      neuroprotection in general. A reduced level of DHA is associated with cognitive
      decline during ageing. Different mechanisms for this fundamental DHA role have
      been put forward. Namely, neuroprotectin D1, a DHA derivative, may support brain
      cell survival and repair through neurotrophic, anti-apoptotic, and anti
      inflammatory signalling. Many of the effects of DHA on the neurological system
      may be related to signalling connections, thus leading to the study of the
      related signalolipidomics. Therefore, the present review will focus on the
      influence of DHA deficiency upon ageing, with specific emphasis upon neurological
      disorders related to cognitive function and mental health.

PMID- 27866495
TI  - Commentary on Sharma et al.

PMID- 27866494
TI  - Brucellosis as a neglected disease in a neglected population: a
      seroepidemiological study of migratory nomads in the Fars province of Iran.
AB  - This study assessed the seroprevalence of brucellosis and its risk factors in
      migratory nomads in the Fars province of Iran. Active brucellosis was defined as
      the combination of clinical symptoms, including fever, chills, night sweats,
      headache, low back pain, arthralgia, or myalgia, and positive laboratory testing,
      including either a serum agglutination test (SAT) ?1:80 with a 2-mercaptoethanol
      (2-ME) test ?1:40, or a SAT <1:80 combined with a positive Coombs Wright test
      (CWT) at a titre of at least threefold higher than SAT titre results. For the 536
      participants, the female (316, 59%) to male (220, 41%) ratio was 1.4 and the
      participants' mean age was 32.4 +/- 18.9 (range 1-96) years. Of all participants,
      325 (60.6%) showed clinical symptoms; in symptomatic participants, the Rose
      Bengal plate test was positive in 33 (6.1%) cases, the SAT was positive in 18
      (3.3%) cases, and the 2-ME test was positive in 30 (5.5%) cases. Positive SAT and
      2-ME results were seen in 18 (3.3%) cases, but a negative SAT and a positive CWT
      were found in 36 (6.7%) cases. As a result, active brucellosis was detected in 54
      cases, indicating a prevalence of 10% (95% confidence interval 8-12). In
      conclusion, we determined that brucellosis is a prevalent yet neglected disease
      in this nomadic population. Brucellosis control is not possible as long as these
      high-risk populations remain neglected.

PMID- 27866496
TI  - Building a translational science on children and youth affected by political
      violence and armed conflict: A commentary.
AB  - Articles in this timely Special Section represent an important milestone in the
      developmental science on children and youth involved in political violence and
      armed conflict. With millions of children worldwide affected by past and present
      wars and conflicts, there is an urgent and growing need for research to inform
      efforts to understand, prevent, and mitigate the possible harm of such violence
      to individual children, families, communities, and societies, for present as well
      as future generations. The four programs of research highlighted in this Special
      Section illustrate key advances and challenges in contemporary development
      research on young people growing up in the midst or aftermath of political
      violence. These studies are longitudinal, methodologically sophisticated, and
      grounded in socioecological systems models that align well with current models of
      risk and resilience in developmental psychopathology. These studies collectively
      mark a critically important shift to process-focused research that holds great
      promise for translational applications. Nonetheless, given the scope of the
      international crisis of children and youth affected by political violence and its
      sequelae, there is an urgent global need for greater mobilization of resources to
      support translational science and effective evidence-based action.

PMID- 27866497
TI  - Neurodevelopmental outcomes in infants exposed in utero to antipsychotics: a
      systematic review of published data.
AB  - The proportion of pregnancies exposed to either second-generation antipsychotics
      (SGAs) or first-generation antipsychotics (FGAs) varies between 0.3%-2% of all
      pregnancies, but, until now, little is known about the potential neurobehavioral
      teratogenicity of antipsychotics. Assessing this safety facet is the aim of this
      article. PubMed, Scopus, and Google Scholar were searched for eligible articles.
      PubMed (1954 to May 2016) was searched using several medical subject headings,
      variously combined. PubMed search results were also limited using the search
      filter for human studies published in English. Scopus and Google Scholar searches
      were filtered for article title (antipsychotics/neuroleptics, pregnancy). After
      excluding duplicates, 9,250 articles were identified and 29 met the following
      inclusion criteria: only articles that provided original/primary data on
      neurodevelopmental outcome in human offspring older than 4 months of age,
      independently of the study design, were selected for review. Indeed, some
      relevant neurodevelopmental milestones are achieved at this time. Length of study
      and neurodevelopmental assessment methodology did not influence the study
      selection. Unfortunately, published data on neurodevelopmental teratogenicity of
      SGAs mainly derive from case reports and small case-series studies. Even findings
      emerging from case-control and prospective/retrospective studies are of limited
      clinical relevance because of their small sample sizes. Limited data are also
      available on FGAs. Hence, we have to conclude that the long-term
      neurodevelopmental outcomes for children exposed in utero remain unclear. Low to
      very low quality evidence of retrieved data makes impossible to confirm or
      exclude potential long-lasting untoward effects on infant neurocognitive
      development associate with antenatal exposure to either SGAs or FGAs.

PMID- 27866498
TI  - Emotional insecurity about the community: A dynamic, within-person mediator of
      child adjustment in contexts of political violence.
AB  - Over 1 billion children worldwide are exposed to political violence and armed
      conflict. The current conclusions are qualified by limited longitudinal research
      testing sophisticated process-oriented explanatory models for child adjustment
      outcomes. In this study, consistent with a developmental psychopathology
      perspective emphasizing the value of process-oriented longitudinal study of child
      adjustment in developmental and social-ecological contexts, we tested emotional
      insecurity about the community as a dynamic, within-person mediating process for
      relations between sectarian community violence and child adjustment.
      Specifically, this study explored children's emotional insecurity at a person
      oriented level of analysis assessed over 5 consecutive years, with child gender
      examined as a moderator of indirect effects between sectarian community violence
      and child adjustment. In the context of a five-wave longitudinal research design,
      participants included 928 mother-child dyads in Belfast (453 boys, 475 girls)
      drawn from socially deprived, ethnically homogenous areas that had experienced
      political violence. Youth ranged in age from 10 to 20 years and were 13.24 (SD =
      1.83) years old on average at the initial time point. Greater insecurity about
      the community measured over multiple time points mediated relations between
      sectarian community violence and youth's total adjustment problems. The pathway
      from sectarian community violence to emotional insecurity about the community was
      moderated by child gender, with relations to emotional insecurity about the
      community stronger for girls than for boys. The results suggest that ameliorating
      children's insecurity about community in contexts of political violence is an
      important goal toward improving adolescents' well-being and adjustment. These
      results are discussed in terms of their translational research implications,
      consistent with a developmental psychopathology model for the interface between
      basic and intervention research.

PMID- 27866499
TI  - Commentary on Huesmann et al.

PMID- 27866500
TI  - Coping and mental health outcomes among Sierra Leonean war-affected youth:
      Results from a longitudinal study.
AB  - This study explored how coping with war-related traumatic events in Sierra Leone
      impacted mental health outcomes among 529 youth (aged 10-17 at baseline; 25%
      female) using longitudinal data from three time points (Time 1 in 2002, Time 2 in
      2004, and Time 3 in 2008). We examined two types of coping items (approach and
      avoidance); used multiple regression models to test their relations with long
      term mental health outcomes (internalizing behaviors, externalizing behaviors,
      adaptive/prosocial behaviors, and posttraumatic stress symptoms); and used
      mediation analyses to test whether coping explained the relation between previous
      war exposures (being raped, death of parent(s), or killing/injuring someone
      during the war) and those outcomes. We found that avoidance coping items were
      associated with lower internalizing and posttraumatic stress behaviors at Time 3,
      and provided some evidence of mediating the relation between death of parent(s)
      during the war and the two outcomes mentioned above. Approach coping was
      associated with higher Time 3 adaptive/prosocial behaviors, whereas avoidance
      coping was associated with lower Time 3 adaptive/prosocial behaviors. Avoidance
      coping may be a protective factor against mental illness, whereas approach coping
      may be a promotive factor for adaptive/prosocial behaviors in war-affected
      societies. This study has important implications for designing and implementing
      mental health interventions for youth in postconflict settings.

PMID- 27866501
TI  - Promoting children's learning and development in conflict-affected countries:
      Testing change process in the Democratic Republic of the Congo.
AB  - Improving children's learning and development in conflict-affected countries is
      critically important for breaking the intergenerational transmission of violence
      and poverty. Yet there is currently a stunning lack of rigorous evidence as to
      whether and how programs to improve learning and development in conflict-affected
      countries actually work to bolster children's academic learning and
      socioemotional development. This study tests a theory of change derived from the
      fields of developmental psychopathology and social ecology about how a school
      based universal socioemotional learning program, the International Rescue
      Committee's Learning to Read in a Healing Classroom (LRHC), impacts children's
      learning and development. The study was implemented in three conflict-affected
      provinces of the Democratic Republic of the Congo and employed a cluster
      randomized waitlist control design to estimate impact. Using multilevel
      structural equation modeling techniques, we found support for the central
      pathways in the LRHC theory of change. Specifically, we found that LRHC
      differentially impacted dimensions of the quality of the school and classroom
      environment at the end of the first year of the intervention, and that in turn
      these dimensions of quality were differentially associated with child academic
      and socioemotional outcomes. Future implications and directions are discussed.

PMID- 27866502
TI  - Dysphoric mania, mixed states, and mania with mixed features specifier: are we
      mixing things up?
AB  - Various terms have been used to describe mania when it is accompanied by
      depressive symptoms. In this article, we attempt to define and discuss 3 of these
      terms: dysphoric mania, mixed state, and mania with mixed features specifier. We
      conclude that whatever term is used, it is important to be aware that mania is
      more often unpleasant than pleasant, and that the unpleasantness is not limited
      to depression.

PMID- 27866503
TI  - Controlling feeding practices and maternal migrant background: an analysis of a
      multicultural sample.
AB  - OBJECTIVE: Parental feeding practices shape children's relationships with food
      and eating. Feeding is embedded socioculturally in values and attitudes related
      to food and parenting. However, few studies have examined associations between
      parental feeding practices and migrant background. DESIGN: Cross-sectional study.
      Parental feeding practices (restriction, pressure to eat, monitoring) were
      assessed using the Child Feeding Questionnaire. Differences were explored in four
      sub-samples grouped by maternal place of birth: Sweden, Nordic/Western Europe,
      Eastern/Southern Europe and countries outside Europe. Crude, partly and fully
      adjusted linear regression models were created. Potential confounding variables
      included child's age, gender and weight status, and mother's age, weight status,
      education and concern about child weight. SETTING: Malmo and Stockholm, Sweden.
      SUBJECTS: Mothers (n 1325, representing seventy-three countries; mean age 36.5
      years; 28.1 % of non-Swedish background; 30.7 % with overweight/obesity; 62.8 %
      with university education) of pre-school children (mean age 4.8 years; 50.8 %
      boys; 18.6 % with overweight/obesity). RESULTS: Non-Swedish-born mothers, whether
      European-born or non-European-born, were more likely to use restriction. Swedish
      born mothers and Nordic/Western European-born mothers reported lower levels of
      pressure to eat compared with mothers born in Eastern/Southern Europe and mothers
      born outside Europe. Differences in monitoring were small. Among the potential
      confounding variables, child weight status and concern about child weight were
      highly influential. Concern about child weight accounted for some of the effect
      of maternal origin on restriction. CONCLUSIONS: Non-European-born mothers were
      more concerned about children being overweight and more likely to report
      controlling feeding practices. Future research should examine acculturative and
      structural factors underlying differences in feeding.

PMID- 27866504
TI  - Oxytocin Reduces Face Processing Time but Leaves Recognition Accuracy and Eye
      Gaze Unaffected.
AB  - OBJECTIVES: Previous studies have found that oxytocin (OXT) can improve the
      recognition of emotional facial expressions; it has been proposed that this
      effect is mediated by an increase in attention to the eye-region of faces.
      Nevertheless, evidence in support of this claim is inconsistent, and few studies
      have directly tested the effect of oxytocin on emotion recognition via altered
      eye-gaze Methods: In a double-blind, within-subjects, randomized control
      experiment, 40 healthy male participants received 24 IU intranasal OXT and
      placebo in two identical experimental sessions separated by a 2-week interval.
      Visual attention to the eye-region was assessed on both occasions while
      participants completed a static facial emotion recognition task using medium
      intensity facial expressions. RESULTS: Although OXT had no effect on emotion
      recognition accuracy, recognition performance was improved because face
      processing was faster across emotions under the influence of OXT. This effect was
      marginally significant (p<.06). Consistent with a previous study using dynamic
      stimuli, OXT had no effect on eye-gaze patterns when viewing static emotional
      faces and this was not related to recognition accuracy or face processing time.
      CONCLUSIONS: These findings suggest that OXT-induced enhanced facial emotion
      recognition is not necessarily mediated by an increase in attention to the eye
      region of faces, as previously assumed. We discuss several methodological issues
      which may explain discrepant findings and suggest the effect of OXT on visual
      attention may differ depending on task requirements. (JINS, 2017, 23, 23-33).

PMID- 27866505
TI  - Ultrastructural Localization of Intracellular Calcium During Spermatogenesis of
      Sterlet (Acipenser ruthenus).
AB  - Calcium regulates many intracellular events such as growth and differentiation
      during different stages of gamete development. The aim of this study was to
      localize and quantify the intracellular distribution of calcium during different
      developmental stages of spermatogenesis in sterlet, Acipenser ruthenus, using a
      combined oxalate-pyroantimonate technique. The distribution of calcium was
      described in spermatogonium, spermatocyte, spermatid, and spermatozoon stages. In
      the spermatogonium and spermatocyte, calcium deposits were mainly localized in
      the nucleus and cytoplasm. The spermatid had calcium in the nucleus, developing
      acrosomal vesicle, and cytoplasm. Intracellular calcium transformed from
      scattered deposits in spermatogonia and spermatocyte stages into an unbound form
      in spermatid and the spermatozoon. The proportion of area covered by calcium
      increased significantly (p<0.05) from early to late stages of spermatogenesis.
      The largest proportion of area covered by calcium was observed in the nucleus of
      the spermatozoon. In conclusion, although most of the intracellular calcium is
      deposited in limited areas of the spermatogonium and spermatocyte, it is present
      an unbound form in the larger area of spermatids and spermatozoa which probably
      reflects changes in its physiological function and homeostasis during the process
      of male gamete production in spermatogenesis.

PMID- 27866506
TI  - The surprising blindness in modern psychiatry: do guidelines really guide?

PMID- 27866508
TI  - New directions for psychiatric rehabilitation in the USA.
AB  - American researchers have led the world in developing, evaluating, and
      disseminating evidence-based psychiatric rehabilitation practices for people with
      serious mental illness. Paradoxically, however, the USA lags behind most
      industrialized nations in providing access to high-quality mental health and
      psychiatric services. This essay examines several evidence-based practices
      developed in the USA, the spread of these practices, the barriers to ensuring
      availability to people who could benefit from these services, and some promising
      directions for overcoming the barriers. Factors influencing the growth and
      sustainment of effective client-centred practices include the availability of
      adequate and stable funding, committed leadership, and the influence of vested
      interests. Two strategies for promoting the spread and sustainment of well
      implemented evidence-based practices are the adoption of fidelity scales and
      learning communities.

PMID- 27866507
TI  - Simulation and Web-based learning increases utilization of Bier block for forearm
      fracture reduction in the pediatric emergency department.
AB  - OBJECTIVES: Bier block (BB) is a safe and effective alternative to procedural
      sedation for analgesia during forearm fracture reductions, yet remains
      infrequently used in the pediatric emergency department (PED). No standardized
      methods of BB training have previously been described. The objective of this
      study was to determine whether a multimodal instructional course increases
      comfort with BB and translates to increased use of this technique. METHODS: A
      novel interdisciplinary simulation and Web-based training course was developed to
      teach the use of BB for forearm fracture reduction at a tertiary PED.
      Participants were surveyed pre-/post-training, and at 2 and 6 months regarding
      their comfort with BB. In parallel, we prospectively assessed the clinical use of
      BB for children ages 6 to 18 years requiring closed reduction of forearm
      fractures during the 24-month post-course period. RESULTS: Course participation
      included 26 physicians and 12 nurses. Survey response rate was 100%. Course
      participation increased both comfort (10% pre-training v. 89% post-training,
      p<0.001) and the willingness to use BB (51% pre-training v. 95% post-training,
      p<0.001), an effect sustained at 6 months post-course (66% and 92%, respectively,
      p<0.001 for both). In clinical practice, there were no BBs performed prior to
      course administration. We observed a consistent and sustained increase in
      clinical use among the BB-trained physicians, with 37% of all forearm reductions
      performed using BB at 24 months post-course completion. CONCLUSIONS: A novel
      combined simulation and Web-based training course increased comfort and
      willingness to use BB and was associated with increased use of this technique for
      forearm fracture reduction in the PED.

PMID- 27866509
TI  - Assistive Technology and Older Adults in Disasters: Implications for Emergency
      Management.
AB  - This article identifies concepts, trends, and policy gaps in the availability and
      service delivery of assistive technology utilized by older adults in disasters,
      as well as implications for emergency management planning and shelter
      administration. Definitions of types of assistive technology, as well as views of
      older adults using technology as at-risk individuals for emergency management
      service provision, are provided. An overview of peer-reviewed articles and gray
      literature is conducted, focusing on publications from 2001 to the present in the
      United States. Analytical frameworks used by emergency management organizations
      as well as regulations such as the Americans with Disabilities Act and recent
      court decisions on emergency shelter accessibility in disasters are reviewed.
      Research on the use of assistive technology by older adults during disasters is a
      neglected issue. The current and potential benefits of defining standards for
      provision and use of assistive technology for older adults during disasters has
      received limited recognition in emergency management planning. Older adults with
      disabilities utilize assistive technology to maintain their independence and
      dignity, and communities as well as emergency services managers need to become
      more aware of the needs and preferences of these older adults in their planning
      processes and drills as well as in service delivery during actual events.
      (Disaster Med Public Health Preparedness. 2017;11:135-139).

PMID- 27866510
TI  - Cancer incidence in young and middle-aged people with schizophrenia: nationwide
      cohort study in Taiwan, 2000-2010.
AB  - AIMS: For nearly a century, the incidence of cancer in people with schizophrenia
      was lower than in the general population. In the recent decade, the relationship
      between cancer and schizophrenia has become obscured. Thus, we investigated the
      cancer risk among young and middle-aged patients with schizophrenia. METHODS:
      Records of newly admitted patients with schizophrenia (n = 32 731) from January
      2000 through December 2008 were retrieved from the Psychiatric Inpatient Medical
      Claims database in Taiwan, and the first psychiatric admission of each patient
      during the same period was defined as the baseline. We obtained 514 incident
      cancer cases that were monitored until December 2010. Standardised incidence
      ratios (SIRs) were calculated to compare the risk of cancer between those with
      schizophrenia and the general population. Stratified analyses of cancer
      incidences were performed by gender, site of cancers and duration since baseline
      (first psychiatric admission). RESULTS: The incidence of cancer for all sites was
      slightly higher than that of the general population for the period (SIR = 1.15
      [95% CI 1.06-1.26], p = 0.001). Men had a significantly higher incidence of
      colorectal cancer (SIR = 1.48 [95% CI 1.06-2.06], p = 0.019). Women had a higher
      incidence of breast cancer (SIR = 1.47 [95% CI 1.22-1.78], p < 0.001).
      Intriguingly, the risk for colorectal cancer was more pronounced 5 years after
      the first psychiatric admission rather than earlier (SIR = 1.94 [1.36-2.75], p <
      0.001) and so was the risk for breast cancer (SIR = 1.85 [1.38-2.48], p < 0.001).
      The cancer incidence was higher in patients with schizophrenia contradicting the
      belief that schizophrenia was protective of cancers. CONCLUSIONS: Our analyses
      suggest that men and women with schizophrenia were more vulnerable to certain
      types of cancers, which indicates the need for gender-specific cancer screening
      programs. The fact that risk of colorectal cancer was more pronounced 5 years
      after the first psychiatric admission could imply the impact of unhealthy
      lifestyles or the possibility of delayed diagnoses.

PMID- 27866511
TI  - Impaired phagocytosis of apoptotic cells causes accumulation of bone marrow
      derived macrophages in aged mice.
AB  - Accumulation of tissue macrophages is a significant characteristic of disease
      associated chronic inflammation, and facilitates the progression of disease
      pathology. However, the functional roles of these bone marrow-derived macrophages
      (BMDMs) in aging are unclear. Here, we identified agedependent macrophage
      accumulation in the bone marrow, showing that aging significantly increases the
      number of M1 macrophages and impairs polarization of BMDMs. We found that age
      related dysregulation of BMDMs is associated with abnormal overexpression of the
      anti-inflammatory interleukin-10. BMDM dysregulation in aging impairs the
      expression levels of pro-inflammatory cytokines and genes involved in B-cell
      maturation and activation. Phagocytosis of apoptotic Jurkat cells by BMDMs was
      reduced because of low expression of phagocytic receptor CD14, indicating that
      increased apoptotic cells may result from defective phagocytosis of apoptotic
      cells in the BM of aged mice. Therefore, CD14 may represent a promising target
      for preventing BMDM dysregulation, and macrophage accumulation may provide
      diagnostic and therapeutic clues. [BMB Reports 2017; 50(1): 43-48].

PMID- 27866514
TI  - [Paraneoplastic Leukocytosis and Thrombocytosis as Prognostic Biomarkers in Non
      small Cell Lung Cancer].
AB  - BACKGROUND: Search for inexpensive laboratory markers have identified
      associations between blood counts and lung cancer outcomes. In this study, we
      evaluated the prognostic value of paraneoplastic leukocytosis (p-Leukocytosis)
      and paraneoplastic thrombocytosis (p-Thrombocytosis) in patients with non-small
      cell lung cancer (NSCLC). We also studied their relation to the expression of
      commonly detected molecular markers. METHODS: We conducted a retrospective chart
      review on 571 consecutive NSCLC patients over a 10 year period. Blood counts were
      recorded at the time of cancer diagnosis. Kaplan-Meier survival curves were used
      to compare overall survival (OS) between patients with and without p-Leukocytosis
      (or) p-Thrombocytosis (p-Leuko/Thrombocytosis). Cox regression was used to
      determine if leukocytosis/thrombocytosis was a predictor of OS in NSCLC. RESULTS:
      Patients with p-Leukocytosis and p-Thrombocytosis had a significantly poorer
      survival compared patients with normal blood counts (P<0.001). In a multivariate
      survival analysis, both continued to correlate even when adjusted for histology,
      gender, stage and chemotherapy (P<0.01, 0.03 respectively). Stage I and II NSCLC
      with p-Leuko/Thrombocytosis did not perform poorly compared to stage I/II NSCLC
      patients without paraneoplasia. Patients with the combined leukothrombocytosis
      syndrome did not have worse outcomes compared to those with either paraneoplastic
      syndrome alone. CONCLUSIONS: p-Leuko/Thrombocytosis is an accessible laboratory
      parameter of prognostic value in NSCLC. Evidence of p-Leuko/Thrombocytosis
      portends poor survival. The role of various cytokines in tumor pathobiology
      provides a rationale for identifying cytokine factors responsible for the
      paraneoplasia and administering anti-cytokine therapies alongside traditional
      chemotherapy in an attempt to improve survival outcomes in these subset of
      patients.

PMID- 27866512
TI  - Age-related epigenetic regulation in the brain and its role in neuronal diseases.
AB  - Accumulating evidence indicates many brain functions are mediated by epigenetic
      regulation of neural genes, and their dysregulations result in neuronal
      disorders. Experiences such as learning and recall, as well as physical exercise,
      induce neuronal activation through epigenetic modifications and by changing the
      noncoding RNA profiles. Animal models, brain samples from patients, and the
      development of diverse analytical methods have broadened our understanding of
      epigenetic regulation in the brain. Diverse and specific epigenetic changes are
      suggested to correlate with neuronal development, learning and memory, aging and
      age-related neuronal diseases. Although the results show some discrepancies, a
      careful comparison of the data (including methods, regions and conditions
      examined) would clarify the problems confronted in understanding epigenetic
      regulation in the brain. [BMB Reports 2016; 49(12): 671-680].

PMID- 27866513
TI  - [Experts Consensus on Huisheng Oral Solution for Lung Cancer ?Anticoagulation
      Treatment at Perioperation Period (2016 version)].

PMID- 27866515
TI  - [Outcomes and Toxicity of Concurrent Radiotherapy with Carboplatin/Paclitaxel
      ?Administrated Every Three Weeks in Inoperable Advanced ?Non-small Cell Lung
      Cancer: ?A Retrospective Study from A Single Center].
AB  - BACKGROUND: Standard care for patients with inoperable advanced non-small cell
      lung cancer (NSCLC) is concurrent chemoradiotherapy. The ideal concurrent
      chemotherapy regimen has not been determined. The aim of this study is to
      retrospectively analyze the efficacy and safety of concurrent radiotherapy with
      carboplatin/paclitaxel administrated every three weeks (PC three-week regimen) in
      inoperable advanced NSCLC and compare them with the results of
      cisplatin/etoposide. METHODS: The 43 patients with inoperable advanced NSCLC
      receiving concurrent chemotherapy in Peking Union Medical College Hospital from
      January 2012 to June 2014 were enrolled and analyzed. Of them, 15 patients
      received carboplatin/paclitaxel with concurrent thoracic radiotherapy; the other
      28 patients received cisplatin/etoposide. Clinical characteristic, efficacy and
      toxicity data were compared in these two groups. RESULTS: For the overall
      population, the objective response rate (ORR) and disease control rate (DCR) were
      41.9% and 90.7% respectively. The median progression free survival (PFS) was 10.6
      months (95%CI: 7.4-13.8). And the median overall survival (OS) was 19.2 months
      (95%CI: 15.3-23.1). There were no significant differences in response rates (ORR:
      33.3% vs 46.4%; DCR: 86.7% vs 92.9%, P=0.638), PFS (6.6 months vs 12.2 months,
      P=0.389), or OS (16.1 months vs 22.1 months, P=0.555) in either group. The
      adverse events were generally manageable and no treatment-related deaths
      occurred. CONCLUSIONS: Compared with PE, PC three-week regimen concurrent
      thoracic radiotherapy for inoperable advanced NSCLC has the similar efficacy and
      acceptable toxicity profile, which can be used in clinical setting.

PMID- 27866516
TI  - [GSI Quantitative Parameters: Preoperative Diagnosis of Metastasis Lymph Nodes in
      Lung Cancer].
AB  - BACKGROUND: Mediastinal involvement in lung cancer is an important prognostic
      factor affecting survival, and accurate staging of the mediastinum lymph node
      correctly identifies patients who can benefit the most from surgery. The aim of
      this study is to investigate the value of dual-energy spectral computed
      tomography (DEsCT) imaging in differentiating metastatic from non-metastatic
      lymph nodes in lung cancer. METHODS: Forty-eight patients with non-small cell
      lung cancer (NSCLC) underwent arterial (AP) and portal venous (PP) phase contrast
      enhanced DEsCT imaging followed by surgical treatment. gemstone spectral imaging
      (GSI) data images were reconstructed and transmitted to an offline workstation.
      GSI quantitative parameters, including lymph-node size, CT value, IC, water
      concentration, and spectral curve. Differences were tested for statistical
      significance using the two-sample t test. ROC analysis was performed to assess
      diagnostic performance. RESULTS: The mean short-axis diameter of metastatic LNs,
      slope of the spectral Hounsfield unit curve (lambdaHU), normalized iodine
      concentration measured during, and both AP and PP were significantly higher in
      metastatic lymph node than that in benign lymph nodes. The best parameter for
      detecting metastatic lymph nodes was AP lambdaHU when a threshold lambdaHU of
      2.75 was used; sensitivity, specificity, and accuracy were 88.2%, 88.4%, and
      87.0%, respectively. CONCLUSIONS: Quantitative assessment with gemstone spectral
      imaging quantitative parameters showed higher accuracy than the qualitative
      assessment of conventional CT imaging features for the preoperative diagnosis of
      metastatic lymph nodes in patients with lung cancer.?.

PMID- 27866517
TI  - [Impact and Effect of Preoperative Short-term Pulmonary Rehabilitation Training
      on ?Lung Cancer Patients with Mild to Moderate Chronic Obstructive Pulmonary
      Disease: ?A Randomized Trial].
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is proposed as an effective strategy to
      decrease surgical morbidity. However, appropriate rehabilitation plan, initiation
      time, and optimal duration of PR remain unclear. Lung cancer patients with
      chronic obstructive pulmonary disease (COPD) are considered high-risk population
      for postoperative pulmonary complications (PPCs) because of poor lung fitness and
      cardiopulmonary endurance. This study aims to assess the impact of a one-week,
      systematic and highly-intensive rehabilitation on surgical lung cancer patients
      with mild to moderate COPD. METHODS: A randomized controlled trial with 48
      subjects was conducted (24 patients each for the intervention and groups). The
      intervention group received seven days of systematic, integrated and highly
      intensive PR before surgical treatment, including: pharmacotherapy with atomizing
      terbutaline, pulmicort and infusion of ambroxol; and physical rehabilitation with
      respiratory training and endurance training. The control group underwent standard
      preoperative care. RESULTS: For the intervention group, the postoperative length
      of stay was shorter [(6.17+/-2.91) d vs (8.08+/-2.21) d; P=0.013]; likewise for
      the duration of antibiotics use [(3.61+/-2.53) d vs (5.36+/-3.12) d; P=0.032]. No
      significant difference was found between the groups in total in-hospital cost
      [(46,455.6+/-5,080.9) Y vs (45,536.0+/-4,195.8) Y, P=0.498], medicine cost
      [(7,760.3+/-2,366.0) vs (6,993.0+/-2,022.5), P=0.223], and material cost
      [(21,155.5+/-10,512.1) Y vs (21,488.8+/-3,470.6) Y, P=0.883]. In the intervention
      group, peak expiratory flow [(268.40+/-123.94) L/min vs (343.71+/-123.92) L/min;
      P<0.001], 6-min walk distance (6-MWD) [(595.42+/-106.74) m vs (620.90+/-99.27) m;
      P=0.004], and energy consumption [(59.93+/-10.61) kcal vs (61.03+/-10.47) kcal;
      P=0.004] were statistically different after the seven-day exercise, compared with
      those on the first day. Finally, for the intervention group the incidence of PPCs
      (8.3%, 2/24 vs 20.8%, 5/24, 20.8%; P=0.416) were lower. CONCLUSIONS: The
      systematic and highly-intensive pulmonary rehabilitation combining abdominal
      respiration training, respiratory exercise with incentive spirometry, and aerobic
      exercise could improve the cardiorespiratory endurance of lung cancer patients
      with mild to moderate COPD. The proposed program may be a practicable
      preoperative strategy.?.

PMID- 27866518
TI  - [Expression of LncRNA AK09398 and Relationship with Prognosis in Patients with
      Small Cell Lung Cancer].
AB  - BACKGROUND: Small cell lung cancer (SCLC) accounts for approximately 15% of lung
      cancer. The poor prognosis of SCLC patients is attributed to the early blood and
      lymph node metastasis. However, the mechanism of SCLC is still unclear. Recent
      studies show that LncRNA plays an important role in the development, metastasis,
      and apoptosis of tumor. Thus, the present study aimed to investigate the
      expression and clinical significance of LncRNA AK09398 in SCLC. METHODS:
      Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used
      to detect the expression of LncRNA AK09398 in 118 cases of SCLC and non-cancerous
      tissues. qRT-PCR was also utilized to analyze the relationship between the
      expression and clinical pathological characteristics and prognosis of SCLC.
      RESULTS: The expression of LncRNA AK09398 in lung cancer tissues was (7.813+/
      0.373). This value was significantly increased in paracarcinoma tissues (1.782+/
      0.116) and normal lung tissues (1.209+/-0.200). The difference was statistically
      significant (F=58.41, P<0.001). AK09398 expression was positively correlated with
      disease stage, lymph node and distant metastasis, chemosensitivity, and survival
      status (P<0.05). However, AK09398 expression was not associated with gender and
      age (P>0.05). Kaplan-Meier analysis demonstrated that high expression level of
      AK09398 contributed to poor overall survival (P<0.001) and progression-free
      survival (P<0.001). The multivariate survival analysis also indicated that
      AK09398 expression, disease stage, and distant metastasis could be independent
      prognostic markers. CONCLUSIONS: LncRNA AK09398 is involved in the development of
      SCLC and can be used as a molecular marker to evaluate the prognosis of SCLC.?.

PMID- 27866519
TI  - [Role of Fucosylation in Cancer].
AB  - Fucosylation is one of the most important glycosylation in mamal, involving
      biosynthesis of blood H antigen and Lewis antigen, selectin mediated intravasion
      and homing of leukocyte, host-microbe interactions, modification of signaling.
      Alterations in the expression of fucosylated oligosaccharides have been observed
      in several cancer, playing a role in proliferation, invasion, metastasis, immune
      escape and drug-sensitiity, especially in lung cancer. Targeting the abnormality
      of fucosylaion in cancer will become a new strategy. The role of fucosylation in
      cancer will be reviewed in this article.

PMID- 27866520
TI  - [Research Advancement on EGFR Mutation Detection of Cell-free DNA and Tumor Cell
      in Peripheral Blood of Patients with Non-small Cell Lung Cancer].
AB  - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer.
      Epideral growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the
      most important treatments currently for advanced NSCLC patients harboring
      activating EGFR gene mutations, and achieve significant clinical efficacy. T790M
      mutation occurs in half of NSCLC patents with acquired EGFR-TKI resistance.
      Screening for EGFR gene mutations in histological and/or circulating tumor cell
      or DNA samples of NSCLC patients can identify patients who would have a response
      to EGFR-TKIs or acquire resistance during the treatment. Quantitative analysis of
      plasma EGFR mutation is of great importance not only in early diagnosis of
      tumors, but also in curative effect evaluation and for follow-up. However, a
      strict requirement is proposed on the detection technique because of low DNA
      content and the fragmentation of the genes. To date, many methods have been
      applied to detect cfDNA EGFR mutations, including sequencing, real-time PCR (RT
      PCR), amplification refractory mutation system (ARMS), mutant-enriched PCR (ME
      PCR), denaturing high-performance liquid chromatography (DHPLC), digital PCR, and
      droplet digital PCR (ddPCR). However, of all the methods above, ddPCR has the
      highest sensitivity, allows high throughput operation. In conclusion, the ddPCR
      has a lot of future promise in clinical gene diagnosis.

PMID- 27866521
TI  - [Progressions on Diagnosis and Treatment of Ground-glass Opacity].
AB  - Pulmonary ground-glass opacity (GGO) has raised increasing attention of clinical
      oncologists and thoracic surgeons in recent years. GGO appears as hazy increased
      opacity of lung, with preservation of bronchial and vascular margins. GGO is less
      opaque than consolidation, in which bronchovascular margins are obscured. In most
      cases, GGOs are indolent, while in other cases, they may grow malignant. This
      pattern makes it difficult to find a standard way to treat patients with GGO.
      Moreover, with the improvement of technology, more and more GGOs are found in
      patients' computed tomgraphy (CT) scan, making it a global problem. In the
      literature, many clinicians have reported their findings on this topic from
      histologic, radiologic and therapeutic perspectives. In this study, we reviewed
      the development on this topic in recent 10 years. We hope our study can be
      helpful for clinicians to better understand this problem, collect more data in
      their clinical work and most importantly, let evidence guide our future
      therapeutic choices.

PMID- 27866525
TI  - [Peripheral T cell lymphoma treatment in the precision medicine era].

PMID- 27866522
TI  - [Research Progress of Exosomes in Lung Cancer Diagnosis and Treatment].
AB  - As the leading cause of morbidity and cancer related-death worldwide, lung cancer
      has a serious threat to human health. Exosomes are nanoscale lipid membrane
      vesicles derived from multivesicles, which containing active biomolecules
      including proteins, lipids, nucleic acids and etc. Exosomes play important roles
      in lung cancer initiation and progression by promoting the formation of tumor
      microenvironment, enhancing tumor invasive and metastasis capability, leading to
      immunosuppression and resistance to chemoradiotherapy, and also have the
      application value in early diagnosis and treatment. This review summarizes the
      research progress of exosomes in tumor initiation and progression, and its roles
      in diagnosis and treatment of lung cancer.

PMID- 27866526
TI  - [Decipher the 2016 revision of the World Health Organization classification of
      lymphoid neoplasms].

PMID- 27866523
TI  - [Progress on the Therapeutic Approaches for Malignant Tumor ?with Superior Vena
      Cava Syndrome].
AB  - Patients with thoracic malignant tumors often suffered from superior vena cava
      syndrome (SVCS), featured by high morbidity and mortality. Traditionally treated
      with palliative approaches, SVCS has been widely studied and novel therapeutic
      approaches have been investigated, focusing on drug therapy, interventional
      therapy, radiation therapy, surgery and proton therapy. In this manuscript, the
      progress of therapeutic approaches for SVCS is summarized.

PMID- 27866524
TI  - [Effect and Significance of BIM on Non-small Cell Lung Cancer].
AB  - B-cell lymphoma 2 interacting mediator of cell death (BIM) plays an important
      role in the progress of cell apoptosis. The lowering expression level or
      functional defect of which may have an negative effect on the efficacy of
      anticancer drugs and the prognosis of postoperative patients with non-small cell
      lung cancer (NSCLC). This review aims to summarize the structure and function of
      BIM, as well as the relationship between BIM and the therapeutic efficacy of
      NSCLC.

PMID- 27866527
TI  - [Association between daytime sleepiness and hypertension among patients with
      obstructive sleep apnea-hypopnea syndrome].
AB  - Objective: To assess the association between daytime sleepiness and hypertension
      among patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods: A
      total of 1 958 patients from Sleep Medicine Center of West China Hospital between
      January 2015 and January 2016 were included in the study. All subjects underwent
      one night polysomnography (PSG) and Epworth sleep scale (ESS) was estimated. The
      patients were divided into non-OSAHS group[apnea-hypopnea index (AHI)<5/h]and
      OSAHS group (AHI>=5/h) based on PSG, and then OSAHS group was further divided
      into those with and without daytime sleepiness groups according to ESS score (the
      cut point of ESS was 14). The association between blood pressure and risk of
      suffering from hypertension among patients with different degree of daytime
      sleepiness was explored by binary logistic regression. Results: There were 1 580
      men and 378 women among the included patients, the mean age was (44.3+/-11.6)
      years old and the mean body mass index (BMI) was (26.4+/-3.8) kg/m2. Among these
      patients, there were 267 non-OSAHS and 1 691 OSAHS patients (1 275 without
      daytime sleepiness and 416 with daytime sleepiness). The prevalence of
      hypertension was higher among OSAHS patients (53.9%vs 28.8%) than non-OSAHS
      group, and OSAHS patients had higher systolic blood pressure (SBP)[(126.3+/-0.4)
      vs (116.3+/-4.9) mmHg], diastolic blood pressure (DBP)[(82.4+/-0.3) vs (78.1+/
      3.7) mmHg]and mean arterial pressure (MAP)[(97.0+/-0.3) vs (90.9+/-3.9) mmHg]than
      non-OSAHS group. And OSAHS with daytime sleepiness also had elevated DBP[(84.5+/
      0.6) vs (81.7+/-0.3) mmHg]and MAP[(98.8+/-0.6) vs (96.5+/-0.3) mmHg]than those
      without sleepiness (all P<0.05). After controlling for age, sex, BMI, smoking,
      drinking, AHI and related sleep parameters, OSAHS combined with daytime
      sleepiness increased the odds of hypertension by 23% (OR=1.23, 95% CI: 1.01-1.65)
      compared to OSAHS without daytime sleepiness. Conclusion: The daytime sleepiness
      is an independent risk factor of hypertension in OSAHS patients.

PMID- 27866528
TI  - [Effect of non-invasive NAVA on the patients with acute exacerbation of chronic
      obstructive pulmonary disease].
AB  - Objective: To observe the effect of non-invasive neurally adjusted ventilatory
      assist (NIV-NAVA) on patient-ventilator synchrony and effect of gas exchange in
      patients with acute exacerbation of chronic obstructive pulmonary disease
      compared with NIV-pressure support ventilation (PSV). Methods: This was a
      prospective study of 40 patients with AECOPD given 30-min trials of NIV with NIV
      PSV group (n=20) and NAVA group (n=20) in random order. Arterial blood gas
      analysis (ABGs), main asynchrony events and asynchrony index were quantified.
      Results: There were no significant difference between the two groups on effect of
      gas exchange (P>0.05). Main asynchrony events during NIV-NAVA including
      autotriggering, ineffective efforts and double triggering were less frequent than
      NIV-PSV (P<0.05). The trigger delay in the NIV-NAVA group was markedly shorter
      than the NIV-PSV (62.20+/-8.91 vs 112.65+/-15.10)ms (P<0.001). The
      inspiratory/expiratory off-cycle delay was significantly shorter in the NIV-PSV
      group than that in the NIV-NAVA group (73.00+/-18.27 vs 187.95+/-39.24)ms
      (P<0.001). The occurrence of severe asynchrony (AI>10%) was also less under NAVA
      (P<0.05). Conclusions: Both NIV-NAVA and NIV-PSV can improve gas exchange. As
      compared with NIV-PSV, NIV-NAVA can reduce main asynchrony events, improve
      patient-ventilator synchrony in patients with AECOPD.

PMID- 27866529
TI  - [A Fisher discriminant model to predict the outcome of postoperative blood
      pressure in primary aldosteronism].
AB  - Objective: To establish a Fisher discriminant model in order to predict the
      outcome of postoperative blood pressure for primary aldosteronism (PA). Methods:
      A total of 83 cases from the First Affiliated Hospital of Chongqing Medical
      University were enrolled and divided into two groups: cure group and not cure
      group according to postoperative blood pressure. Fisher stepwise discriminant
      analysis was used to establish a discriminant model, and compared with
      aldosteronoma resolution score (ARS) and nomogram model by receiver operating
      characteristic curve. Results: Hypertension was cured in 52 cases, and 31 cases
      remained uncured. Patients in uncured group were older, and had bigger body mass
      index (BMI), longer duration of hypertension, higher serum triglyceride (TG),
      more types of antihypertensive drug, higher incidence of diabetes, smoking and
      alcohol intake, less typical nodules on computed tomography imaging, lower
      estimated glomerular filtration rate (eGFR) and high density lipoprotein
      cholesterol. The discriminant model based on BMI, types of antihypertensive
      drugs, typical nodules on CT, eGFR and TG was established and the cut-off value
      was 0.195 9, with a sensitivity of 86.5% and a specificity of 83.9%. The area
      under the curve was 0.857 (95% CI: 0.764-0.951), which was higher than that of
      ARS (0.733, 95% CI: 0.619-0.847) and the nomogram model (0.735, 95% CI: 0.619
      0.851). Conclusion: The Fisher discriminant model had a high value to predict the
      outcome of postoperative blood pressure in PA.

PMID- 27866530
TI  - [Comparison of the prognosis after hepatic resection for patients with Barcelona
      Clinical Liver Cancer Stage B hepatocellular carcinoma].
AB  - Objective: To compare the efficacy of hepatic resection (HR) in patients with
      Barcelona Clinical Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and
      examine how that efficacy has changed over time in a large medical center.
      Methods: A consecutive sample of 918 patients with preserved liver function and
      large and/or multinodular HCC who were treated by initial HR were divided into
      three groups: those with a single tumor >=5 cm in diameter (n=582), 2-3 tumors
      with a maximum diameter>3 cm (n=223), or>3 tumors of any diameter (n=113).
      Hospital mortality and overall survival (OS) in each group were compared for the
      years 2001-2007 and 2008-2013. Results: Patients with >3 tumors showed the
      highest incidence of hospital mortality of all groups (P<0.05). Kaplan-Meier
      survival analysis showed that OS varied across the three groups as follows:
      single tumor>2-3 tumors >3+ tumors (all P<0.05). OS rate at 5 years ranged from
      24% to 41% in all three groups for the period 2001-2007, and from 35% to 46% for
      the period 2008-2013. OS was significantly higher during the more recent 6-year
      period in the entire patient population, those with single tumor, and those with
      3+ tumors (all P<0.05). However, in patients with 2-3 tumors, OS was only
      slightly higher during the more recent 6-year period (P=0.084). Conclusions:
      Prognosis of three types of HCC was different. Patients with >3 tumors show the
      highest hospital mortality and lowest OS after HR. OS has been improving for all
      three types of HCC at our medical center as a consequence of improvements in
      surgical technique and perioperative management.

PMID- 27866531
TI  - [Effect of 10-Hydroxycamptotbecine on the proliferation of human Fibroblast-like
      Synoviocyte with Rheumatoid Arthritis].
AB  - Objective: To study the effect of 10-Hydroxycamptothecine (10-HCPT) on the
      proliferation and apoptosis of human Fibroblast-like Synoviocyte (FLS) with
      Rheumatoid Arthritis (RA). Methods: Different concentrations of 10-HCPT and
      Methotrexate (MTX) were used to treat FLS cells in RA and Osteoarthritis (OA) for
      different time (24, 48, and 72 hours), and FLS cells without 10-HCPT and MTX were
      served as the control group. CCK-8 assay were applied to determine the
      proliferation of FLS cells, Annexin-V APC/7-AAD staining were used to detect the
      apoptosis of FLS cells. Results: The survival rate of FLS cells were (66.68+/
      0.48) %, 48 h; (60.09+/-0.95) %, 72 h and (44.05+/-1.29) %, 48 h; (30.63+/-1.79)
      %, 72 h, when the concentrations were 1.0 MUg/ml and 10.0 MUg/ml in 10-HCPT
      group. Compared with the control group, the survival rate of FLS cells in RA and
      OA both declined in treatment groups with different concentrations of 10-HCPT and
      MTX. With the extension of time, the survival rate of FLS cells declined
      significantly. Compared with the MTX group, there were no obvious differences in
      10-HCPT group with 1.0 MUg/ml. But the concentration of 10.0 MUg/ml of 10-HCPT
      group showed obviously difference in the proliferation of FLS cells. The
      apoptosis rate of FLS cells were (66.68+/-0.48) %, 48 h; (60.09+/-0.95) %, 72 h
      and (44.05+/-1.29) %, 48 h; (30.63+/-1.79) %, 72 h, when the concentrations were
      1.0 MUg/ml and 10.0 MUg/ml in 10-HCPT group. Compared with the control group, two
      concentrations of 10-HCPT and MTX induced higher apoptosis in FLS cells with RA
      and OA; with the extension of time (72 h), the rate of apoptosis was
      significantly enhanced (P<0.05). When FLS cells with RA were treated for 48 h,
      apoptosis of 10-HCPT group was higher than that of MTX group. The 10.0 MUg/ml of
      10-HCPT had the highest effect. Conclusion: Compared with MTX, 10-HCPT had the
      higher efficacy of inhibiting proliferation and promoting apoptosis in FLS cells.

PMID- 27866532
TI  - [Evaluation of disease free survival after radical resection for primary duodenal
      adenocarcinoma].
AB  - Objective: To investigate the risk factors associated with the disease free
      survival (DFS) for primary duodenal adenocarcinoma patients undergoing radical
      resection. Methods: The clinicopathological data of 101 primary duodenal
      adenocarcinoma patients who underwent radical resection from January 2001 to
      October 2014 were retrospectively reviewed. Using SPSS 13.0 software, the
      survival curve was drawn by Kaplan-Meier method, and the survival rates were
      analyzed by Log-rank test.COX regression model was used to identify independent
      risk factors. Results: Among 101 patients, the main clinical manifestation were
      upper abdomen discomfort, abdominal pain, jaundice, gastrointestinal obstruction,
      hemorrhage, emaciation and so on. A total of 87 patients had the tumor located at
      the descending part of the duodenum. All the 101 patients underwent radical
      resection, and 85 patients received pancreatoduodenectomy while 16 patients
      underwent segmental resection. The median disease free survival time was 26
      months and the postoperative 1, 3, 5 year DFS rate were 79.7%, 60.3% and 53.6%,
      respectively. The univariate analyses identified elevated preoperative CEA and
      CA19-9 level, T stage, lymph node state, vascular invasion and perineural
      invasion predicting a worse DFS(P<0.05). On multivariate analysis, positive lymph
      node state was an independent risk factor for DFS (RR=5.394, 95% CI: 1.624
      17.913). Conclusion: Radical resection is the best therapeutic method for primary
      duodenal adenocarcinoma; the positive lymph node state is the independent risk
      factor affecting the disease free survival of patients after radical resection.

PMID- 27866533
TI  - [LB100 reverses the acquired resistance to gefitinib in lung adenocarcinoma cells
      with EGFR mutation].
AB  - Objective: To investigate the possibility of the Protein Phosphatase 2A (PP2A)
      inhibitor, LB100, in reversing acquired resistance to gefitinib in lung
      adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutation.
      Methods: Cell line NCI-H1975 and established primary culture cell line 44-1 with
      gefitinib resistance were sequenced to determine the mutation type of EGFR gene.
      Cells were treated with gefitinib alone or combined with LB100 to determine the
      half maximal inhibitory concentration (IC50), and sensitivity of 44-1 and NCI
      1975 to gefitinib alone or combined with LB100 was compared. The volume of NCI
      H1975 xenografts with different drug treatments was observed to determine the
      efficiency of gefitinib with or without LB100 in tumor growth inhibition.
      Results: Both 44-1 and NCI-1975 cells had double EGFR mutation (sensitive L858R
      mutation and resistant T790M mutation). Both cells showed significant gefitinib
      resistance (IC50: 23.0 MUmol/L in 44-1, 16.7 MUmol/L in NCI-1975). When combined
      with LB100, IC50 of gefitinib decreased to 6.9 MUmol/L in 44-1 cell and decreased
      to 3.4 MUmol/L in NCI-H1975 cells. In NCI-1975 xenografts experiments, LB100
      enhanced the ability of gefitinib in tumor growth inhibition (P<0.05).
      Conclusion: LB100 reverses acquired resistance to gefitinib in lung
      adenocarcinoma cell lines.

PMID- 27866535
TI  - [Regulatory analysis of hypoxia on innate immunity of human corneal epithelium].
AB  - Objective: To investigate the role of hypoxia on the regulation of innate
      immunity of human corneal epithelium. Methods: Telomerase-immortalized human
      epithelial cells (THCEs) were incubated under normoxia (21% O2) or hypoxic (1%
      O2) conditions respectively. After 6, 12, 24, 48 h culture, the mRNA and protein
      levels of toll like receptor 4 (TLR4) were measured by real-time polymerase chain
      reaction (RT-PCR) and Western blot analysis. After 24 h culture, THCEs of each
      group were challenged respectively with TLR4 ligand lipopolysaccharide (LPS) (1
      MUg/ml) for 6 h. RT-PCR was used to assess the mRNA level of myeloid
      differentiation factor 88 (MyD88), interleukin(IL)6, IL-8 and tumor necrosis
      factor alpha (TNF-alpha). Western blot was used to examine the protein level of
      inhibitor of nuclear factor kappa-B alpha (IkappaBalpha) and phosphorylated
      IkappaBalpha (p-IkappaBalpha). Enzyme-linked immunosorbent assay (ELISA) was used
      to detect the secretion of the inflammatory cytokines IL-6, IL-8 and TNF-alpha.
      Results: The results of RT-PCR and Western blot analysis showed that the
      expression of TLR4 downregulated 90% and 55% respectively after hypoxic exposure
      for 48 h. Hypoxia also inhibited LPS-induced secretion of IL-6, IL-8, TNF-alpha,
      expression of MyD88 and activation of NF-kappaB. The mRNA level of MyD88 was
      diminished 63%, and the protein expression of p-IkappaBalpha was also lowered.
      Meanwhile, the secretions of IL-6, IL-8 and TNF-alpha under hypoxia were reduced
      (31%, 55% and 50% respectively). Conclusion: Hypoxia attenuated immune and
      inflammatory response of the cornea epithelium by suppressing TLR4 signaling, and
      could enhance cell susceptibility to microorganism infection.

PMID- 27866534
TI  - [Dihydrotestosterone inhibits foam cell formation via a lectin-like ox-low
      density lipoprotein receptor mediated mechanism in J774.1 cell line].
AB  - Objective: To investigate the effect of dihydrotestosterone (DHT) on lectin-like
      ox- low-density lipoprotein (LDL) receptor(LOX-1)expression and foam cell
      formation in the female macrophage cell line J774.1. Methods: In cultured J774.1
      cells, after pretreated with DHT at concentrations of 1*10-9 mol/L and 1*10-8
      mol/L, ox-LDL-induced LOX-1 expression and foam cell formation were investigated
      by quantitative real-time PCR, Western blotting, and oil-red O staining. Results:
      DHT at concentrations of 1*10-9 mol/L and 1*10-8 mol/L inhibited ox-LDL-induced
      LOX-1 mRNA (2.81+/-0.46 and 2.29+/-0.21 vs 4.71+/-0.31, both P<0.01) and protein
      expression (1.35+/-0.06 and 1.09+/-0.04 vs 1.75+/-0.11, both P<0.05). The effect
      was partly reversed by the androgen receptor (AR) blocker flutamide (87.6%,
      P=0.004). Oil-red O staining also revealed that DHT at concentrations of 1*10-9
      mol/L and 1*10-8 mol/L suppressed ox-LDL-induced foam cell formation as
      quantified by the number of foam cells per high-power field (HPF) (36.0+/-3.0 and
      29.1+/-1.3 vs 45.9+/-3.7, both P<0.05) and by the area of oil-red O stained
      particles per HPF (7 983+/-1 035 and 4 060+/-390 vs 14 750+/-2 489, both P<0.05).
      Conclusion: DHT at concentrations of 1*10-9 mol/L and 1*10-8 mol/L decreases LOX
      1 expression and foam cell formation via AR.

PMID- 27866536
TI  - [In vivo and in vitro experimental studies of remote digital control endovascular
      robotic system in interventional angiography].
AB  - Objective: To investigate the feasibility of the remote control endovascular
      robotic system in interventional angiography. Method: The endovascular robotic
      system HeifetzTM and the matched steerable catheter MirageTM were used to
      cannulate all the target vessels in the vascular model and cerebral arteries
      originated from the aorta of Bama mini-pigs under fluoroscopic guidance. The
      technical success rate, cannulation time and exposure dose were all collected and
      compared with the result of using conventional techniques. Result: All the target
      vessels were successfully cannulated.The average cannulation time for the
      steerable catheter into left subclavian artery, left common carotid artery,
      brachiocephalic artery, right common carotid artery and right subclavian artery
      in the vascular model was (21.3+/-2.8)s, (28.8+/-5.2)s, (17.7+/-2.6)s, (31.5+/
      5.1)s and (24.2+/-3.7) s, respectively, while the average exposure dose was
      (9.3+/-1.2)mGy, (12.4+/-2.2)mGy, (7.4+/-1.2)mGy, (14.2+/-2.5)mGy and( 10.4+/
      1.9)mGy, respectively. The endovascular robotic system completed the cerebral
      angiography in Bama mini-pigs successfully. The average cannulation time for left
      innominate artery, right innominate artery, right subclavian artery, common
      internal carotid trunk, left internal carotid artery and right internal carotid
      artery was (41.5+/-6.8)s, (29.1+/-3.7)s, (40.7+/-5.5)s, (40.1+/-5.8)s, (59.6+/
      9.0)s and( 60.3+/-10.1)s, respectively, while the average exposure dose was
      (40.6+/-6.5)mGy, (36.0+/-5.2)mGy, (39.8+/-6.1)mGy, (43.9+/-6.7)mGy, (51.0+/
      7.4)mGy and( 50.1+/-7.8)mGy, respectively. There was no significant difference
      between robotic and conventional group in success rate, cannulation time and
      exposure dose. Conclusion: The remote digital control endovascular robotic system
      could cannulate the target vessel in both vascular model and complete the
      cerebral angiography in Bama mini-pigs, which shows the feasibility of using this
      robotic system in endovascular intervention procedures under remote control.

PMID- 27866537
TI  - [Asbestos related diseases: a challenge for occupational health].

PMID- 27866538
TI  - [Respiratory protection provided by N95 filtering facepiece respirators and
      disposable medicine masks against airborne bacteria in different working
      environments].
AB  - Objective: To determine the relative protection provided by N95 filtering
      facepiece respirators (FFR) and disposable medicine masks (DMM) against airborne
      bacteria in different working environments. Methods: The field study was
      performed with 12 subjects wearing an N95 filtering facepiece respirator and a
      disposable medicine mask for 1h, respectively. Airborne microorganisms and
      bacteria samples from both the external (Ce) and the inner (Ci) surface of N95
      FFR and DMM are collected. The Ce: Ci ratio was used to calculate the bacterial
      filtering proportion. Bacterial filtering efficiency (BFE) was measured using the
      JWL-2A Sampler. Results: The bacterial filtration efficiency of N95 FFR and DMM
      were 99.93% and 91.53%, respectively. There was significant difference between
      the two materials (P<0.05). In summer, airborne bacterial concentration was
      higher than that in winter. In the same season, airborne bacterial concentration
      in hospital environment is higher than that in campus. The higher the airborne
      bacterial concentration, the greater bacterial contaminated on the external
      surface of the used masks. To all masks used in different working environment,
      bacterial contamination on the external surface was much greater than the inner
      surface (P<0.01). Compared to N95 FFR, DMM had slighter bacterial contamination
      on the external surface and greater bacterial contamination on the inner surface.
      However, this difference was not significant (P>0.05). The bacterial filtering
      proportion of N95 FFR is higher than DMM. These differences were significant in
      samples tested in summer (P<0.05) , but were not significant in samples tested in
      winter (P>0.05). Conclusion: Bacterial filtering efficiency of N95 respirator is
      superior to medicine mask, and this advantage become more obvious in high
      airborne bacterial concentration levels.

PMID- 27866539
TI  - [The relationships of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) inhalational dose and oxidative damage in foundry workers].
AB  - Objective: To investigate the potential dose-response relationship between
      PCDD/Fs inhalational exposure and oxidative damage to DNA and lipid in foundry
      workers. Methods: The participants were divided into three groups, including
      exposure group, administrator group and control group. The concentrations of
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in air environment
      were determined by isotope dilution high resolution capillary column gas
      chromatography/high resolution mass spectrometry (HRGC-HRMS). The inhalational
      dose of PCDD/Fs were evaluated by Houmen's model. Urinary 8-OHdG was analyzed by
      high performance liquid chromatography-electrochemical detector (HPLC-ECD).
      Urinary 8-iso-PGF2alpha were determined by ELISA. Results: The PCDD/Fs
      environmental concentrations of three groups (pg.TEQ/m) were 0.21+/-0.08, 0.03+/
      0.01, 0.0012+/-0.0007 (P<0.05) , respectively. The inhalational dose of exposure
      group (92.54 (32.90~264.49) fg.TEQ/kg.d) was 5.4 folds higher than the
      administrator group, and was 201 times more than control group. The levels of
      urinary 8-OHdG (nmol/L crea) of three groups were 3.25 (1.07~15.36) , 2.72
      (0.75~16.07) , 2.17 (0.38~17.07) (P<0.05) and the levels of urinary 8-iso
      PGF2alpha (nmol/L crea) were 19.11 (9.33~76.50) , 20.95 (8.40~79.31) , 11.48
      (4.85~37.80) (P<0.05) , respectively. The multiple linear regression analysis
      revealed that there were significantly increased trend for levels of urinary 8
      OHdG and 8-iso-PGF2alpha as PCDD/Fs exposure levels increased, after adjustment
      for age, sex, smoking statue, alcohol use and BMI (P<0.01). Conclusion: There was
      a dose-response relationship between PCDD/Fs inhalational exposure and oxidative
      damage in foundry workers.

PMID- 27866541
TI  - [Influencing factors for postoperative survival of patients with stage III
      silicosis treated by lung transplantation].
AB  - Objective: To investigate the clinical effect, postoperative complications, and
      causes of death in the treatment of stage III silicosis with lung transplantation
      and the influencing factors for survival. Methods: A retrospective analysis was
      performed for the clinical data of 32 patients with stage III silicosis who
      underwent lung transplantation in our hospital from September 2002 to September
      2015. The survival, causes of death, and postoperative complications were
      analyzed. The Kaplan-Meier method was used to plot survival curves, the log-rank
      test was used to compare the influence of each factor on survival rates, and the
      multivariate Cox proportional hazards regression model was used to evaluate the
      influence of each factor on survival. Results: All the patients underwent
      successful lung transplantation. The 3-month and 1-, 3-, and 5-year postoperative
      cumulative survival rates were 90.6%, 80.8%, 76.7%, and 76.7%, respectively.
      Eight patients died during the postoperative follow-up, among whom 1 died of
      multiple organ failure, 3 died of severe infection, 2 died of sudden cardiac
      death, 1 died of renal failure, and 1 died of bronchiolitis obliterans. The major
      postoperative complications included primary graft dysfunction (PGD) in 10
      patients, severe infection in 7 patients, acute rejection reaction in 3 patients,
      bronchiolitis obliterans in 5 patients, bleeding in 5 patients, anastomotic
      complication in 2 patients, and renal dysfunction in 3 patients. The Kaplan-Meier
      survival analysis showed that sex, postoperative PGD, postoperative infection,
      massive intraoperative blood loss, preoperative pulmonary arterial hypertension
      were influencing factors for postoperative survival rates (P<0.05). The
      multivariate Cox regression model showed that male sex was the protective factor
      (P<0.05) and postoperative PGD and massive intraoperative blood loss were
      independent risk factors for death after transplantation (P<0.05). Conclusion:
      Lung transplantation is a method for the treatment of silicosis. Postoperative
      PGD and massive intraoperative blood loss are independent risk factors for death
      after transplantation. Survival rates are affected by postoperative PGD,
      infection, massive intraoperative blood loss, and preoperative pulmonary arterial
      hypertension.

PMID- 27866542
TI  - [Analyse coal workers' pneumoconiosis deaths reported in Beijing since 1997 to
      2014].

PMID- 27866540
TI  - [The study of the eosinophil CD34+ progenitor cells differentiation mechanism of
      model rats with occupational asthma and the intervention of warm and tonifying
      kidney yang decoction].
AB  - Objective: To investigate the mechanism of CD34+ progenitor cell differentiation
      in rat by observing the change relations between the eosinophils (EOS) and the
      content of Eotaxin and IL-5 in blood and the CD34+/CCR3+, CD34+/IL-5Ralpha+ in
      bone marrow after occupational asthma (OA) model rats are simulated, and to
      observe the effect of WTKYD Trraitional Chinese Medicine intervention. Methods: A
      total of 40 healthy male SD model rats (200~250 g weight) were randomly divided
      into model contrast Group, prednisone acetate intervention Group, WTKYD+1/2
      prednisone acetate intervention Group and WTKYD intervention Group, 10 in each
      group, and set a Group for blank contrast. Give them saline (20 ml/kg) ,
      prednisone acetate (8.22 mg/kg) , WTKYD (20g/kg) +1/2 prednisone acetate (4.11
      mg/kg) and WTKYD (20 g/kg) intervention respectively. By means of cell count,
      immunohistochemical, ELISA, flow cytometry technique, situ hybridization and so
      on, to observe EOS and the expression of Eotaxin in lung tissue, the EOS in
      peripheral blood, the content of Eotaxin and IL-5 in blood as well as the
      expression of CD34+/CCR3+ and CD34+/IL-5Ra+ in bone marrow respectively. Results:
      The number of EOS, the content of Eotaxin and IL-5, the expression of CD34+/CCR3+
      and CD34+/IL-5Ra+ in Model Contrast Group were higher in Blank Contrast Group,
      the difference was statistically significant (P<0.01) , while they were lower in
      medical intervention Groups when comparing to Model Contrast Group, the
      difference was statistically significant (P<0.01 or P<0.05) , and the above items
      in WTKYD+1/2 Prednisone Acetate Intervention Group were even lower than in
      Prednisone Acetate Intervention Group and WTKYD Intervention Group, the
      difference was statistically significant (P<0.05). EOS in lung tissue is highly
      positive related to the content of Eotaxin and IL-5 in peripheral blood as well
      as the expression of CD34+/CCR3 and CD34+/IL-5Ralpha in bone marrow
      (0.9666,0.9829,0.9142, 0.8874). Conclusion: The increase of internal EOS in lung
      tissue is related to the up-regulated expression of CD34+/CCR3+ and CD34+/IL-5Ra+
      in bone marrow after antigens in Occupational Asthma model rats are stimulated.
      Through down-regulating it's expression to restrain the differentiation of CD34+
      progenitor cells towards EOS, meanwhile, the collaboration of WTKYD and
      prednisone acetate possess a certain synergistic action.

PMID- 27866543
TI  - [Influence of coke oven emissions on workers' blood pressure and
      electrocardiographic findings].
AB  - Objective: To investigate the influence of coke oven emissions on workers' blood
      pressure and electrocardiographic findings, and to provide a basis for the
      prevention and treatment of cardiovascular diseases. Methods: The concentration
      of coke oven emissions at the bottom, side, and top of coke ovens was determined
      in a coking plant. A total of 406 coke oven workers were enrolled as exposure
      group and 201 office staff members were enrolled as control group. Blood pressure
      and electrocardiographic findings were compared between the two groups, and the
      multivariate logistic regression analysis was performed to analyze the
      influencing factors for hypertension and abnormal electrocardiographic findings.
      Results: The concentration of coke oven emissions was the highest at the top of
      coke ovens, followed by the side and bottom of coke ovens, and there was a
      significant difference between the exposure group and the control group (P<0.01).
      The exposure group had significantly higher detection rates of hypertension,
      abnormal electrocardiographic findings, and abnormal chest X-ray findings than
      the control group (P<0.05). The logistic regression analysis showed that high
      concentration of coke oven emission and age were risk factors for hypertension
      and abnormal electrocardiographic findings (P<0.05). The workers exposed to high
      concentration coke oven emissions were more likely to experience hypertension and
      abnormal electrocardiographic findings than those exposed to low-concentration
      coke oven emissions (OR=1.7 and 1.9). Conclusion: Besides lung injury, coke oven
      emissions also have adverse effects on the cardiovascular system. Therefore, more
      effective measures are needed to protect the health of coke oven workers.

PMID- 27866544
TI  - [Effects of chronic exposure to monochloroacetic acid on the lung function and
      lymphocyte subsets in occupational exposed workers].
AB  - Objective: To investigate the effects of chronic exposure to monochloroacetic
      acid on the lung function and whole blood counts in occupational exposed workers,
      and provide new markers for occupational health surveillance. Methods: We
      conducted a cross-sectional molecular epidemiology study of 121 workers who were
      occupationally exposed to monochloroacetic acid and 69 unexposed workers
      frequency-matched by age and smoking status from the same geographic region. The
      lung function was measured by portable lung function instrument, and the
      lymphocyte subsets were measured by flow cytometry. Linear regression was used to
      test for differences in the levels of each marker between exposed and control
      workers. Results: FEV1.0/FVC was significantly decreased in both male and female
      workers exposed to monochloroacetic acid compared to unexposed workers (P<0.01)
      after adjusting for potential confounders, which were highly consistent when
      stratified by smoking status. Among male workers, monochloroacetic acid exposure
      was associated with significant decrease in the levels of CD8+ T cells (P<0.05)
      and monocytes (P<0.05) , and these statistically significant differences were
      observed between exposure and control workers only among smokers, not among non
      smokers. However, there were no significant differences in the levels of whole
      blood cells and lymphocyte subsets between two groups among female workers.
      Conclusion: The chronic monochloroacetic acid exposure was associated with
      pulmonary dysfunction and immunosuppression, which mainly occurred among male
      workers and smokers.

PMID- 27866545
TI  - [Value of low-dose multi-slice spiral CT chest scan in diagnosis of coal workers'
      pneumoconiosis].
AB  - Objective: To investigate the value of low-dose multi-slice CT (MSCT) chest scan
      in the diagnosis of coal workers' pneumoconiosis. Methods: A total of 90 patients
      with a confirmed diagnosis of coal workers' pneumoconiosis were enrolled, and
      under the conditions of fixed tube voltage, pitch, and slice thickness, they
      underwent CT scan with a normal dose (150 mA) and a low dose (30-50 mA). The
      quality of images obtained from two scans was compared, and the imaging findings,
      opacity profusion, stage, and radiation doses were also compared. Results:
      Compared with the normal-dose scan, low-dose scan increased the image noise, and
      the images obtained from scans with doses of 30, 40, and 50 mA did not show
      significant reductions in signal-to-noise ratio or contrast-to-noise ratio
      (P>0.05). There was no significant difference in the percentage of image quality
      between low-dose and normal-dose scans (P>0.05). There were no significant
      differences in the percentage of various imaging findings, opacity profusion, or
      percentage of different stages between low-dose (30, 40, and 50 mA) and normal
      dose (150 mA) scans (P>0.05). Conclusion: There are no significant differences
      between low-dose MSCT chest scan and normal-dose CT in image quality, imaging
      findings of coal workers' pneumoconiosis, opacity profusion, and stage.
      Meanwhile, low-dose MSCT chest scan greatly reduces the radiation dose and can be
      used to assist the diagnosis and follow-up reexamination of coal workers'
      pneumoconiosis and cover the shortage of high-kilovoltage chest X-ray.

PMID- 27866546
TI  - [Application of principal component analysis in comprehensive indicator screening
      for pneumoconiosis in different regions].
AB  - Objective: To investigate the application of principal component analysis in
      comprehensive indicator screening for pneumoconiosis in different regions.
      Methods: A principal component analysis was performed for the data of 11 factors
      associated with the prediction of pneumoconiosis hazard and collected in the
      investigation on occupational health status conducted in 172 counties (districts)
      in Hebei, China. The degree of pneumoconiosis hazard in different regions was
      obtained and intuitively presented by GIS. Results: The eigenvalues of 5
      principal components of pneumoconiosis were 4.103, 2.341, 0.981, 0.943, and
      0.726, respectively, and the contribution values were 37.299%, 21.286%, 8.919%,
      8.572%, and 6.596%, respectively. According to the comprehensive value of
      principal components, GIS Natural Breaks was used to divide the degree of
      pneumoconiosis hazard in 172 counties (districts) in Hebei into mild, moderate,
      and severe grades. Of all the counties, 46 had severe pneumoconiosis hazard, 69
      had moderate pneumoconiosis hazard, and 57 had mild pneumoconiosis hazard, and
      the ranges of the score of principal components were 0.30-1.15, -0.24 to 0.27,
      and -0.69 to -0.25, respectively. Conclusion: Principal component analysis can
      optimize the comprehensive indicators for the evaluation of regional
      pneumoconiosis. The comprehensive score of principal components can quantify and
      intuitively show the degree of pneumoconiosis hazard in different regions.
      Tangshan, Chengde, Shijiazhuang, and Handan have the most severe pneumoconiosis
      hazard.

PMID- 27866547
TI  - [Prevalence of pneumoconiosis in a coal enterprise from 2002 to 2013].
AB  - Objective: To investigate the prevalence of pneumoconiosis in a coal enterprise,
      and to provide a basis for the prevention and treatment of pneumoconiosis.
      Methods: The workers' occupational health examination data were collected, and a
      cross-sectional study was performed to analyze the prevalence of pneumoconiosis.
      Results: A total of 62 976 person times of occupational health examination were
      performed for the workers exposed to dust in this enterprise from 2002 to 2013.
      There were 8 445 cases of pneumoconiosis diagnosed in total, and the mean
      detection rate was 13.41%. Of all patients with pneumoconiosis, 3 262 died. The
      mean detection rate was 8.98% among in-service workers and 19.64% among retired
      workers. The mean age of onset was (52.6+/-11.3) years, and the mean working age
      of onset was (18.4+/-10.1) years. Conclusion: The detection rate of
      pneumoconiosis is high in the retired workers in this enterprise, and medical
      follow-up for retired workers and those who have left their jobs should be taken
      seriously.

PMID- 27866548
TI  - [Effect of heme oxygenase-1 transduced by cell penetrating peptide PEP-1 on renal
      injury in rats with acute paraquat poisoning].
AB  - Objective: To study the effects of heme oxygenase-1 transduced by cell
      penetrating peptide PEP-1 on renal injury in acute paraquat-induced rats.
      Methods: The fusion protein PEP-1/HO-1 was manufactured by genetic engineering
      methods. One hundred and twenty-six healthy adult Sprague-Dawley (SD) rats (63
      male, 63 female) were randomly divided into three groups: (1) Control group: 42
      rats, (2) Poisoned group: 42 rats, (3) PEP-1/HO-1 intervention group: 42 rats.
      The rats in Poisoned group and intervention group were treated intraperitoneally
      with paraquat (25 mg/kg) deliquated with normal saline. Control group rats were
      treated with the same way of normal saline as the others. Intervention group rats
      were injected 1 mg of the fusion protein PEP-1/HO-1 into the left iliac vein at
      30 minutes before the administration of the paraquat. After abdominal dissection
      with ether anaesthesia, six rats respectively from each of three groups were
      taken tissue samples from kidney at 1 st,6 th,12 th,24 th,36 th,48 th,and 72 nd
      hour respectively. Tissue Superoxide Dismutase (SOD) activity and Malondialdehyde
      (MDA) content were measured, and renal tissue was quickly remained to observe the
      expression of Heme Oxygenase-1 (HO-1) by the method of immunohistochemistry.
      Blood samples were collected from the abdominal aorta for determination of Blood
      Urea Nitrogen (BUN) and Creatinine (Cr) concentrations in plasma. Results: To
      prepare high purity fusion protein PEP-1/HO-1 Successfully. The levels of the
      plasma Bun and Cr in Poisoned and intervention group were significantly higher
      than that in Control group in the six to seventy-two hours (P<0.01) ; Whereas the
      increases of Bun and Cr were markedly intibited in PEP-1/HO-1 intervention group,
      in which, the levels of Bun and Cr in the six to seventy-two hours were
      significantly lower than Poisoned group (P<0.05). Compared with control group,
      the levels of MDA in poisoned groups were increased in the one to forty-eight
      hours and the levels of it in groups PEP-1/HO-1 in the one to thirty-six (P<0.01
      or P<0.05). The T-SOD activity of the poisoned group was decreased in the one to
      thirty-six hours than that of the control group (P<0.05). Compared with poisoned
      group, the T-SOD activity at various points in time was increased in group PEP
      1/HO-1 (P<0.01). In control group, there was only very weak expressions of HO-1
      in the normal renal tissue. In poisoned and intervention group, the expressions
      of HO-1 were significantly higher than that in control group in all time
      (P<0.01). The HO-1 expressions of PEP-1/HO-1 group in all time was significantly
      higher than that in poisoned group (P<0.01 or P<0.05). Conclusion: The HO-1
      protein Can be successfully transduced into renal tissue by cell penetrating
      peptide PEP-1 and the transduced HO-1 protein reduces renal injury of the acute
      paraquat-induced rats by inhibiting lipid peroxidation response.

PMID- 27866549
TI  - [Characteristics of lung function in patients with asbestosis of different
      stages].
AB  - Objective: To investigate the characteristics of lung function in the patients
      with asbestosis of different stages, and analyze the correlations between the
      pulmonary function values and imaging score of chest X-ray. Methods: A cohort of
      newly diagnosed 249 asbestosis patients over a period of eight years in a single
      center were evaluated. Clinical data were collected from clinical charts.
      Radiographs were reviewed by the experts blinded to clinical data. The asbestosis
      patients were classified into I to III stages by chest X-ray according to the
      guideline. The correlations between the pulmonary function values and imaging
      score of chest X-ray were analyzed. Results: The prevalence of stage I to III in
      this asbestosis cohort was 73.5%, 19.3% and 7.2% respectively. With the stages
      increasing, the patients' forced vital capacity (FVC) , total lung capacity (TLC)
      , total carbon monoxide diffusion capacity (DLCO) predicted values were all
      reduced showing the restrictive ventilation impairment and/or gas exchange
      barrier. The obstruction of the small respiratory tracts was detected in the
      asbestosis of all the different stages. According to the small shadow density of
      each lung area, chest small shadow density score had a significant negative
      correlation with FVC, TLC or DLCO predicted values respectively (all P<0.01).
      Conclusion: The patients with asbestosis of different stages had varying degrees
      of gas exchange impairment, small airway dysfunction with or without ventilation
      dysfunction. The decreasing of DLCO was earlier than lung volume change. Chest X
      ray image score paralleled the decline of lung function values, reflecting the
      severity of the disease.

PMID- 27866550
TI  - [A case of mediastinal emphysema following gastric lavage for oral doxepin
      poisoning].

PMID- 27866551
TI  - [A case of respiatory failue caused by inalation of dichlorvos and chlorpyrifos
      poisoning].

PMID- 27866552
TI  - [Silicosis with tracheobronchopathia osteochondroplastica: one case report].

PMID- 27866553
TI  - [Clinical analysis of five cases of acute naphthalene poisoning].

PMID- 27866554
TI  - [Hemoperfusion for the treatment of toxic hepatitis caused by mushroompoisoning:
      a report of 3 cases].

PMID- 27866555
TI  - [Two cases of acute poisoning of paraquat with dursban and paraquat with
      bromadiolone].

PMID- 27866556
TI  - [Clinical analysis of 5 patients caused by acute inhalation of phosphoric acid
      gas poisoning].

PMID- 27866557
TI  - [52 acute toxic hepatopathy cases induced by tetrachloromethane combined organic
      solvent].

PMID- 27866558
TI  - [Analysis of the reasons for the change in the diagnosis of coal
      workerspneumoconiosis].

PMID- 27866559
TI  - [The founding analysis of national natural science foundation in the field of
      occupational and environmental health].

PMID- 27866560
TI  - [Nonmalignant diseases related to asbestos: a clinical update].

PMID- 27866561
TI  - [Idiopathic pulmonary fibrosis: an update of pharmacological therapy].

PMID- 27866563
TI  - [Recent advance of cytokines in the pathogenesis of lung injury induced by
      paraquat poisoning].

PMID- 27866562
TI  - [The association between gene polymorphisms and genetic susceptibility of the
      pathogenesis of pneumoconiosis].

PMID- 27866564
TI  - Home, Lifestyle and the Burden of Disease.

PMID- 27866565
TI  - Regional Differences in the Prevalence of Cardiovascular Disease.
AB  - BACKGROUND: Cardiovascular disease continues to be the single most common cause
      of death and to account for the largest single portion of treatment costs in
      Germany. Reliable data on regional differences in the frequency of cardio -
      vascular disease are important for the planning of targeted care structures and
      preventive measures. METHODS: Pooled data from the German Health Update (GEDA), a
      nationwide telephone health survey conducted in 2009, 2010 and 2012 (n = 62 214)
      were used to estimate the lifetime prevalence of major cardiovascular disease
      (self-reported medical diagnosis of myocardial infarction, other coronary heart
      disease, stroke, or congestive heart failure) in each of the German federal
      states. The influence of sociodemographic factors on regional prevalence
      differences was examined in adjusted logistic regression analyses. Prevalences
      were compared with mortality rates from cardiovascular disease that were obtained
      from cause-of-death statistics. RESULTS: The lifetime prevalence of
      cardiovascular disease in Germany ranged from 10.0% in Baden-Wrttemberg to 15.8%
      in Saxony-Anhalt. After adjustment for age, sex, socioeconomic status, and size
      of the communities of residence, nine of the other 15 states had significantly
      higher prevalences than Baden-Wrttemberg, with odds ratios ranging from 1.26
      (Hesse) to 1.55 (Saxony-Anhalt). Four of the five states that previously
      constituted the German Democratic Republic (East Germany) had above-average
      figures for prevalence and mortality. CONCLUSION: There are relevant differences
      among the German federal states in the lifetime prevalence of major
      cardiovascular disease, which are only partly accounted for by differences in age
      and sex distribution, socioeconomic status, and community size.

PMID- 27866567
TI  - Large Gaps in Care.

PMID- 27866566
TI  - Time Trends in Cardiometabolic Risk Factors in Adults.
AB  - BACKGROUND: Data from three representative health examination surveys in Germany
      were analyzed to examine secular trends in the prevalence and magnitude of
      cardiometabolic risk factors. METHODS: The target variables were the following
      cardiometabolic risk factors: lack of exercise, smoking, obesity, systolic blood
      pressure, total cholesterol, serum glucose, self-reported high blood pressure,
      hyperlipidemia, and diabetes, and the use of antihypertensive, cholesterol
      lowering, and antidiabetic drugs. 9347 data sets from men and 10 068 from women
      were analyzed. The calculated means and prevalences were standardized to the age
      structure of the German population as of 31 December 2010 and compared across the
      three time periods of the surveys: 1990-1992, 1997-1999, and 2008-11. RESULTS:
      Over the entire period of observation (1990-2011), the mean systolic blood
      pressure fell from 137 to 128 mmHg in men and from 132 to 120 mmHg in women; the
      mean serum glucose concentration fell from 5.6 to 5.3 mmol/L in men and from 5.4
      to 5.0 mmol/l in women; and the mean total cholesterol level fell from 6.2 to 5.3
      mmol/L in both sexes. In men, smoking and lack of exercise became less common. On
      the other hand, the prevalence of use of antidiabetic, cholesterol-lowering, and
      antihypertensive drugs rose over the same time period, as did that of self
      reported diabetes. The first of the three surveys (1990-1992) revealed
      differences between persons residing in the former East and West Germany in most
      of the health variables studied; these differences became less marked over time,
      up to the last survey in 2008-2011. CONCLUSION: The cardiometabolic risk profile
      of the German adult population as a whole improved over a period of 20 years.
      Further in-depth analyses are now planned.

PMID- 27866568
TI  - In Reply.

PMID- 27866569
TI  - Computed Tomography in Germany.
AB  - BACKGROUND: In 2001, calculations in models based on atomic bomb survivors
      indicated that children exposed to ionizing radiation by computed tomography (CT)
      would be expected to have an increased risk of cancer. This led to the issuance
      of new recommendations in Germany concerning CT in children. METHODS: We analyzed
      data from the German pediatric CT cohort study together with data on children
      from a large general statutory health insurance provider (AOK) in order to
      characterize the secular trend in the use of CT in Germany. We used information
      from the Picture Archiving and Communication System (PACS) to estimate individual
      organ doses per scan and their development over time. RESULTS: The number of CT
      scans performed on children in Germany each year declined by 29% from 2006 to
      2012. Over the same period, younger children were exposed to lower organ doses
      during CT scanning, although some organ doses were higher in neonates than in
      older children. The highest organ doses were in the 7.6 to 12.5-year-old age
      group and affected the brain (37.12 mGy +/- 19.68 mGy) and the lenses (41.24 mGy
      +/- 20.08 mGy). In every age group, the organ doses declined from year to year.
      With approximately 21 000 children aged 0-13 undergoing CT each year
      (extrapolated from insurance data of 2008), one can expect 2.3 [-1.7; 6.3]
      additional new cases of leukemia and 1 [-2.3; 4.0] additional new tumor of the
      central nervous system to arise each year. CONCLUSION: In view of the risks,
      children should undergo CT only for the indications listed by the German
      Commission on Radiological Protection (Strahlenschutzkommission). Further
      epidemiological studies are needed for estimation of the risk associated with the
      use of newer CT technology.

PMID- 27866571
TI  - Maintenance of Sterility: A Base of Aseptic Procedures.

PMID- 27866570
TI  - The Diagnosis and Treatment of Peripheral Arterial Vascular Disease.
AB  - BACKGROUND: In peripheral arterial occlusive disease (PAOD), arterial stenosis or
      occlusion impairs perfusion in the territory of the distal portion of the aorta
      and the iliac and leg arteries. In Germany, the prevalence of PAOD rises with
      age, reaching 20% among persons over age 70. METHODS: This guideline was prepared
      by a collaboration of 22 medical specialty societies and two patient self-help
      organizations on the basis of pertinent publications that were retrieved by a
      systematic search in PubMed for articles that appeared from 2008 to April 2014,
      with a subsequent update to May 2015. RESULTS: 294 articles were assessed,
      including 34 systematic reviews and 98 randomized controlled trials (RCTs). The
      diagnostic assessment of PAOD is based on physical examination, blood pressure at
      the ankles, and color-coded duplex ultrasonography (grade A recommendation).
      Other tomographic imaging methods can be used for suitable indications. The main
      elements of the treatment of PAOD are the control of cardiovascular risk factors
      and structured vascular exercise (grade A recommendation). Acetylsalicylic acid
      and statins are the main drugs for symptomatic PAOD (grade A recommendation).
      Patients with claudication and correlated structural findings can undergo an endo
      - vascular or open surgical procedure. Critical ischemia is an indication for
      arterial revascularization as soon as possible (grade A recommendation); this may
      be performed either by open surgery or by an endovascular procedure of one of the
      types that are now undergoing rapid development, or one of the crural treatment
      options. There is inadequate evidence concerning the optimal drug regimen after
      revascularization procedures. CONCLUSION: The diagnostic assessment of PAOD is
      based on physical examination, measurement of the ankle-brachial index (ABI), and
      duplex ultrasonography. Acetylsalicylic acid and statins are indicated for
      patients with symptomatic PAOD. Endovascular procedures should be used if
      indicated. Randomized studies are needed to provide better evidence on many open
      questions in the treatment of PAOD.

PMID- 27866572
TI  - Progressively Reduce the Number of Infections.

PMID- 27866573
TI  - In Reply.

PMID- 27866574
TI  - Welcome to a SUPA issue.

PMID- 27866575
TI  - Anemia for the Primary Care Physician.
AB  - Anemia denotes a reduced red blood cell (RBC) mass from any cause. The causes of
      anemia are numerous and due to decreased (or abnormal) erythropoesis, shortened
      RBC life span, or blood loss. The most common etiology of anemia is iron
      deficiency. A judicious work up of anemia includes evaluating the reticulocyte
      count and peripheral smear. The severity of illness of a patient with anemia is
      determined by the degree of anemia and the seriousness of the underlying
      disorder. Management of patients with hereditary and hemolytic anemias should
      involve a hematologist.

PMID- 27866576
TI  - Thrombocytopenia.
AB  - Thrombocytopenia is a commonly encountered hematologic problem in inpatient and
      ambulatory medicine. The many underlying mechanisms of thrombocytopenia include
      pseudothrombocytopenia, splenic sequestration, and marrow underproduction and
      destruction. This article presents the known causes of thrombocytopenia, a
      framework for evaluation, and brief descriptions of management in a case-based
      format.

PMID- 27866577
TI  - Novel Developments in Leukopenia and Pancytopenia.
AB  - Cytopenias are not disease entities in and of themselves; rather, they are the
      expression of various underlying disease processes. Careful attention to details
      in patients' presentation, careful history and examination, as well as attention
      to the ancillary parameters of the complete blood count with a peripheral blood
      smear can point the clinician toward the appropriate workup. Causes of cytopenias
      can be inherited or acquired; the latter include medication related, autoimmune,
      or neoplastic causes. Emergencies need to be recognized in a timely fashion and
      expert consultation obtained.

PMID- 27866578
TI  - Leukocytosis and Leukemia.
AB  - Leukocytosis is among the most common findings on peripheral blood smear. A wide
      range of causes may mediate this finding, and careful clinical and laboratory
      evaluation assist in differentiating between benign and malignant causes of
      increased white blood cell counts. In this article, various nonmalignant causes
      are explored, including infectious, inflammatory, autoimmune, and allergic. In
      addition, malignant causes of leukocytosis are discussed, including
      myeloproliferative disorders, acute leukemia, and chronic leukemia, as well as
      treatment and monitoring for patients with these diseases.

PMID- 27866579
TI  - Polycythemia and Thrombocytosis.
AB  - Myeloproliferative neoplasms (MPNs) are diseases of excess cell proliferation
      from bone marrow precursors. Two classic MPNs, polycythemia vera (PV) and
      essential thrombocytosis (ET), are conditions of excess proliferation of red
      blood cells and platelets, respectively. Although PV and ET involve different
      cells in the myeloid lineage, their clinical presentations have shared features,
      consistent with overlapping mutations in growth factor signaling. The management
      of both diseases involves minimizing the risk of thrombotic and hemorrhagic
      complications. Both PV and ET can progress to myelofibrosis or acute myeloid
      leukemia, portending a poor prognosis. MPNs can also present as primary
      myelofibrosis.

PMID- 27866580
TI  - Eosinophilia.
AB  - Eosinophilia is defined as elevation of eosinophils in the bloodstream (450-550
      cell/MUL). There are many reasons for eosinophilia to exist, including parasitic
      disease, allergic disease, autoimmune, connective tissue disease, rheumatologic
      disease, primary eosinophilia such as hypereosinophilic syndrome, and as part of
      a malignant state. Primary care physicians should have an understanding of the
      variety of diseases or situations that can produce eosinophilia and know in what
      setting referral to specialty care may be warranted.

PMID- 27866581
TI  - Thrombosis, Hypercoagulable States, and Anticoagulants.
AB  - Patients with derangements of secondary hemostasis resulting from inherited or
      acquired thrombophilias are at increased risk of venous thromboemboli (VTE).
      Evaluation of a patient with suspected VTE proceeds via evidence-based algorithms
      that involve computing a pretest probability based on the history and physical
      examination; this guides subsequent work-up, which can include D dimer and/or
      imaging. Testing for hypercoagulable disorders should be pursued only in patients
      with VTE with an increased risk for an underlying thrombophilia. Direct oral
      anticoagulants are first-line VTE therapies, but they should be avoided in
      patients who are pregnant, have active cancer, antiphospholipid antibody
      syndrome, severe renal insufficiency, or prosthetic heart valves.

PMID- 27866582
TI  - Bleeding Diatheses: Approach to the Patient Who Bleeds or Has Abnormal
      Coagulation.
AB  - Many complex elements contribute to normal hemostasis, and an imbalance of these
      elements may lead to abnormal bleeding. In addition to evaluating medication
      effects, the hematologist must evaluate for congenital or acquired deficiencies
      in coagulation factors and platelet disorders. This evaluation should include a
      thorough bleeding history with careful attention to prior hemostatic challenges
      and common laboratory testing, including coagulation studies and/or functional
      platelet assays. An accurate diagnosis of a bleeding diathesis and selection of
      appropriate treatment are greatly aided by a basic understanding of the
      mechanisms of disease and the tests used to diagnose them.

PMID- 27866583
TI  - Transfusion Medicine.
AB  - Transfusion of various blood components can provide relief from symptomatic
      anemia and reduce the bleeding risks associated with low platelet counts or
      presence of coagulopathy. Blood components are collected from volunteer donors
      and processed into separate components to maximize efficient utilization of a
      scarce resource while also providing maximum clinical benefit. Tests including
      blood type and screening for clinically significant alloantibodies increase the
      likelihood of successful transfusion. Risks of transfusion include
      hypersensitivity and hemolytic transfusion reactions, transfusion-related acute
      lung injury, transfusion-associated circulatory overload, and transmission of
      infection. Indications for transfusion are reviewed along with various products
      available for transfusion.

PMID- 27866584
TI  - Lymphoma.
AB  - Lymphomas may be broadly divided into non-Hodgkin (90%) and Hodgkin (10%) types.
      Most lymphomas (90%) are of B cell origin but can also be T cell or natural
      killer cell. Clinical management of indolent and aggressive lymphomas is
      different. Aggressive lymphomas are more dangerous if left untreated yet a higher
      cell proliferation rate also renders them more chemosensitive, so they are
      managed with curative intent. Indolent lymphomas are, for the most part,
      incurable, such that quality of life must be balanced against toxicity of
      treatment in deciding when and how to treat.

PMID- 27866585
TI  - Plasma Cell Disorders.
AB  - Plasma cell disorders are benign, premalignant, and malignant conditions
      characterized by the presence of a monoclonal paraprotein detected in serum or
      urine. These conditions are biologically, pathologically, and clinically
      heterogeneous. There have been major advances in the understanding of the biology
      of these diseases, which are promoting the development of therapies with novel
      mechanisms of action. Novel agents such as proteasome inhibitors,
      immunomodulatory drugs, and monoclonal antibodies have gained approval in the
      United States and Europe for the treatment of plasma cell disorders. Such
      therapies are translating into higher rates of response and survival and better
      toxicity profiles.

PMID- 27866586
TI  - Basics of Hematopoietic Cell Transplantation for Primary Care Physicians and
      Internists.
AB  - More than 60,000 hematopoietic cell transplantations (HCTs) are annually
      performed worldwide to treat a variety of malignant and nonmalignant conditions.
      Although HCT is complicated and risky, a majority of the HCT recipients are
      surviving for many years post-transplant. This article presents the basics of
      transplantation, HCT types/stem cell sources, mobilization and conditioning
      procedures, indications for HCT, conditioning regimens, engraftment, graft-versus
      host-disease, and survivorship issues.

PMID- 27866587
TI  - Strange Cells.

PMID- 27866588
TI  - Preface.

PMID- 27866589
TI  - Endocrinology, diabetes and nutrition: The future is here.

PMID- 27866590
TI  - Corrigendum to the inextricable axis of targeted diagnostic imaging and therapy:
      An immunological natural history approach [Nucl Med Biol 43 (2016) 215-225].

PMID- 27866591
TI  - Considerations on a New Diagnostic Clue to Osteomyelitis.

PMID- 27866592
TI  - The Reply.

PMID- 27866593
TI  - Zika Virus Infection: Don't Miss It.

PMID- 27866595
TI  - Modifiable Healthy Lifestyle Behaviors: 10-Year Health Outcomes From a Health
      Promotion Program.
AB  - INTRODUCTION: Previous studies have examined the impact of healthy lifestyle
      choices on health-related outcomes; however, given their fragmented, often cross
      sectional nature, assessing the relative impact of daily modifiable behaviors on
      overall long-term outcomes, particularly for a diverse working adult population,
      remains challenging. METHODS: Relationships between ten self-reported healthy
      lifestyle behaviors and health outcomes during the subsequent 9 years in a cohort
      of 10,248 participants enrolled during 2003 in a voluntary workplace wellness
      program were assessed. Cox proportional-hazards models computed hazard ratios
      (HRs) for lifestyle characteristics associated with time to one of seven self
      reported chronic diseases or death. Data were collected between 2003 and 2012 and
      analyzed between 2014 and 2016. RESULTS: Behaviors that most significantly
      affected future outcomes were low-fat diet, aerobic exercise, nonsmoking, and
      adequate sleep. A dose-response effect was seen between dietary fat intake and
      hypertension, obesity, diabetes, heart disease, and hypercholesterolemia. After
      dietary fat intake, aerobic exercise was the next most significant behavior
      associated with development of outcomes. Compared with sedentary participants,
      those who exercised 4 days per week were less likely to develop new-onset
      diabetes (HR=0.31, 95% CI=0.20, 0.48); heart disease (HR=0.46, 95% CI=0.27,
      0.80); and hypercholesterolemia (HR=0.61, 95% CI=0.50, 0.74). Low-fat diet and
      adequate sleep were more significant than commonly promoted healthy behaviors,
      such as eating a daily breakfast. CONCLUSIONS: Modifiable lifestyle behaviors
      targeted in health promotion programs should be prioritized in an evidence-based
      manner. Top priorities for workplace health promotion should include low-fat
      diet, aerobic exercise, nonsmoking, and adequate sleep.

PMID- 27866596
TI  - Clinic and Community: The Road to Integration.
AB  - INTRODUCTION: There is growing recognition of the important role that social and
      environmental conditions play in health, and of the interaction needed between
      clinical providers and the broader community in which patients live, work, play,
      and manage their health. Through the Safety Net Enhancement Initiative, the
      Kresge Foundation funded demonstration projects in eight vulnerable communities
      to address health inequities and increase integration between clinical and
      community systems. METHODS: In 2014, integration efforts in 2011-2013 were
      qualitatively analyzed within and between sites to identify common features. The
      series of steps taken by sites during the 3-year implementation period that were
      necessary to move toward integration were then analyzed. RESULTS: Safety Net
      Enhancement Initiative sites increased capacities within clinics, including
      policy and practice changes that expanded the way "health" is defined by clinical
      providers and the implementation of onsite programs/services. Several sites
      changed clinic policies to support referral to community programs with partner
      organizations. Several sites also successfully changed local community policies
      and practices. Moving toward integration, mechanisms were created to link newly
      developed or identified community resources to the clinical system. CONCLUSIONS:
      As an established system organized around disease treatment, not prevention,
      certain changes need to be made within the clinical system to prepare for
      integration. These changes require shifting perspectives, changing behaviors, and
      developing novel administrative models. Similarly, integration requires changes
      within and among community systems, including organizations, services, and
      residents. Ultimately, there is the need to find ways for these two very
      different environments to interact and coordinate.

PMID- 27866594
TI  - Influenza Vaccination of Healthcare Personnel by Work Setting and Occupation
      U.S., 2014.
AB  - INTRODUCTION: Routine influenza vaccination of healthcare personnel (HCP) can
      reduce influenza-related illness and its potentially serious consequences among
      HCP and their patients. Influenza vaccination has been routinely recommended for
      HCP since 1984. METHODS: Data from the 2013 and 2014 National Health Interview
      Survey were analyzed in 2015. Kaplan-Meier survival estimated the cumulative
      proportion of HCP reporting 2013-2014 season influenza vaccination. Vaccination
      coverage by work setting and occupation were assessed. Multivariable logistic
      regression and predictive marginal analyses identified factors independently
      associated with vaccination among HCP. RESULTS: Influenza vaccination coverage
      was 64.9% among HCP aged >=18 years (95% CI=60.5%, 69.3%), which was
      significantly higher compared with non-HCP among the same age group (41.0%, 95%
      CI=39.8%, 42.1%) (p<0.05). Vaccination coverage was higher among physicians
      (82.3%) and nurses (77.5%) than other types of HCP (range, 50.2%-65.6%). Coverage
      was higher among HCP working in hospitals (76.9%) versus other settings (range,
      53.9%-60.2%). Characteristics independently associated with an increased
      likelihood of vaccination among HCP were older age, higher education, having more
      physician contacts, and having health insurance. Having never been married was
      independently associated with decreased likelihood of vaccination among HCP.
      CONCLUSIONS: Influenza vaccination coverage was higher among HCP than non-HCP,
      but still below the national target of 90%. Vaccination coverage varied widely by
      occupation type, work settings, and demographic characteristics. Evidence-based
      interventions, such as making vaccine available at no cost in the workplace and
      active promotion of vaccination, are needed to increase influenza vaccination
      among HCP in all healthcare settings.

PMID- 27866598
TI  - Never-Smoking Adolescents' Exposure to Secondhand Smoke in Africa.
AB  - INTRODUCTION: Though Africa is in Stage 1 of the tobacco epidemic, lack of
      effective public smoking laws or political will implies that secondhand smoke
      (SHS) exposure may be high in youth. The study objective is to estimate
      prevalence and identify determinants of SHS exposure among never-smoker
      adolescents in Africa and make cross-country comparisons. METHODS: Pooled data
      from the Global Youth Tobacco Surveys conducted in 25 African countries during
      2006-2011 were used. Based on the venue of exposure in past 7 days, SHS was
      categorized into exposure inside, outside, and overall exposure (either inside or
      outside of the home), respectively. Data were analyzed in 2015 using logistic
      regression models to identify factors related to SHS exposure in three venues.
      RESULTS: About 21% and 39% of adolescents were exposed to SHS inside or outside
      of the home, with overall exposure of 45%. In all 25 African countries, parental
      smoking was significantly associated with SHS exposure inside the home (ORs
      ranging from 3.02 [95% CI=2.0, 4.5] to 14.65 [95% CI=10.0, 21.5]). Peer smoking
      was associated with SHS exposure outside the home in 18 countries (ORs ranging
      from 1.45 [95% CI=1.0, 2.1] to 3.00 [95% CI=1.8, 5.1]). Parental smoking, peer
      smoking, and anti-smoking messages in media were identified as three major
      factors associated with SHS exposure. CONCLUSIONS: A significant proportion of
      never-smoking adolescents in Africa are exposed to SHS, suggesting the need for
      countries to adopt policies to protect never smokers through the implementation
      of the WHO Framework Convention on Tobacco Control.

PMID- 27866599
TI  - Correlates of Helmet Use Among Recreation and Transportation Bicyclists.
AB  - INTRODUCTION: Helmet use prevents injury and mortality if a bicyclist is in a
      collision while riding. This cross-sectional study sought to identify domain
      specific (recreation versus transportation) correlates of helmet use among U.S.
      adult bicyclists, using nationally representative data from 2012. METHODS: This
      analysis, conducted in 2015-2016, utilized data from the 2012 National Survey of
      Bicyclist and Pedestrian Attitudes and Behaviors, administered for the National
      Highway Traffic Safety Administration. Bivariate logistic regressions identified
      sociodemographic, behavioral, and environmental correlates of helmet use among
      U.S. adult bicyclists. Backwards elimination procedures selected final
      multivariate models for bicyclists' helmet use in both domains. RESULTS: Among
      recreation cyclists, helmet use was significantly associated with income ($30,000
      $75,000, OR=1.79, 95% CI=1.04, 3.10; >=$75,000, OR=2.34, 95% CI=1.38, 3.97),
      safety training (OR=2.94, 95% CI=1.46, 5.93), not riding at dark (OR=1.92, 95%
      CI=1.24, 2.98), feeling threatened while riding (OR=2.24, 95% CI=1.12, 4.45), and
      using bike lanes/paths (OR=2.04, 95% CI=1.42, 2.93). Helmet use among
      transportation riders was significantly associated with education (less than high
      school, OR=2.45, 95% CI=1.13, 5.32; post-high school, OR=3.55, 95% CI=1.96,
      6.42), income ($30,000-$75,000, OR=2.11, 95% CI=1.17, 3.8; >=$75,000, OR=2.33,
      95% CI=1.26, 4.27), unemployment (OR=0.29, 95% CI=0.11, 0.76), not using
      electronics while riding (OR=2.3, 95% CI=1.41, 3.75), safety training (OR=3.19,
      95% CI=1.44, 7.07), and injury while riding within the past 2 years (OR=2.81, 95%
      CI=1.14, 6.94). CONCLUSIONS: Correlates of helmet use among bicyclists are domain
      specific. Although confirmatory longitudinal studies are needed, findings suggest
      that interventions to increase bicyclists' helmet use consider riding domain.

PMID- 27866597
TI  - Life-course Social Mobility and Reduced Risk of Adverse Birth Outcomes.
AB  - INTRODUCTION: Higher adult socioeconomic position (SEP) is associated with better
      birth outcomes. However, few studies incorporate life-course or intergenerational
      SEP, which may inform etiology and targeted prevention efforts. This study tested
      whether life-course social mobility from childhood was associated with lower risk
      of adverse birth outcomes. METHODS: Data were from the Life-course Influences of
      Fetal Environments (LIFE) retrospective cohort study among black women, 2009
      2011, in metropolitan Detroit, MI. This study (analyzed in 2014-2016) examined
      whether social mobility was associated with two primary birth outcomes: small for
      gestational age (SGA) and preterm birth (PTB). Childhood and adulthood SEP were
      measured by survey in adulthood, for two constructs, measured ordinally:
      educational attainment and perceived financial sufficiency (subjective
      income/wealth). Social mobility was calculated as the difference of adulthood
      minus childhood SEP. RESULTS: In covariate-adjusted Poisson regression models, 1
      SD improved educational social mobility from childhood to adulthood was
      protective for SGA (adjusted risk ratio=0.76; 95% CI=0.64, 0.91); this
      association remained after adjusting for financial mobility. Upward financial
      social mobility from early childhood was marginally protective for SGA (adjusted
      risk ratio=0.85; 95% CI=0.72, 1.02), but became nonsignificant after controlling
      educational mobility. There were no overall associations of social mobility with
      PTB or low birth weight, although sensitivity analyses identified that improved
      financial mobility was associated with 16% marginally lower risk of spontaneous
      PTB and 28% marginally lower risk of low birth weight among upwardly
      mobile/stable women only. CONCLUSIONS: Improved life-course social mobility is
      associated with reduced risk for SGA and spontaneous PTB among black women.

PMID- 27866600
TI  - Maintaining a Healthy BMI: Data From a 16-Year Study of Young Australian Women.
AB  - INTRODUCTION: The aims of this prospective cohort study were to examine 16-year
      trajectories of weight and BMI in young adult women who had a healthy BMI in 1996
      and determinants of remaining in the healthy BMI category. METHODS: A total of
      4,881 women with healthy BMI at baseline and either healthy, overweight, or obese
      BMI at 16-year follow-up reported their weight, height, health, and health
      behaviors in six surveys of the Australian Longitudinal Study on Women's Health
      between 1996 (aged 18-23 years) and 2012 (aged 34-39 years). Determinants of BMI
      maintenance were estimated using binary logistic regression and generalized
      estimating equations in 2015. RESULTS: Almost 60% remained in the healthy BMI
      category from 1996 to 2012, (mean weight gain, 0.19 kg/year), 29% transitioned to
      overweight BMI (0.83 kg/year), and 11.6% transitioned to obese (1.73 kg/year).
      The mean rates of annual weight gain in each group were consistent over time.
      Only three factors (low alcohol, moderate/high physical activity, having a
      university degree) were positively associated with maintaining a healthy BMI.
      Additional behavioral factors (smoking, high sitting time, energy intake,
      dieting, takeaway food, and use of oral contraceptives), as well as blue collar
      occupation, separation/divorce/widowhood, and major illness were negatively
      associated with BMI maintenance. CONCLUSIONS: To prevent the transition from
      healthy to overweight/obese BMI, weight gain must be limited to <0.5 kg/year.
      Women with healthy BMI, but with higher rates of weight gain in their early 20s,
      could be identified by health professionals for assistance with prevention of
      becoming overweight/obese.

PMID- 27866602
TI  - Biosynthetic nanoparticles for biotechnological and biomedical applications.

PMID- 27866601
TI  - Assessment of State Perinatal Hepatitis B Prevention Laws.
AB  - INTRODUCTION: Identifying pregnant women with hepatitis B virus (HBV) infection
      for post-exposure prophylaxis of their infants is critical to preventing mother
      to-child transmission of HBV infection. HBV infection in infancy results in
      premature death from chronic liver disease or cancer in 25% of affected infants.
      Universal screening of pregnant women for HBV infection is the standard of care,
      and in many states is supported by laws for screening and reporting these
      infections to public health. No recent assessment of state screening and
      reporting laws for HBV infection has been published. METHODS: In 2014, the
      authors analyzed laws current through December 31, 2013 from U.S. jurisdictions
      (50 states and the District of Columbia) related to HBV infection and hepatitis B
      surface antigen screening and reporting requirements generally and for pregnant
      women specifically. RESULTS: All states require reporting of cases of HBV
      infection. Twenty-six states require pregnant women to be screened. Thirty-three
      states require public health reporting of HBV infections in pregnant women, but
      only 12 states require reporting pregnancy status of women with HBV infection.
      CONCLUSIONS: This assessment revealed significant variability in laws related to
      screening and reporting of HBV infection among pregnant women in the U.S.
      Implementing comprehensive HBV infection screening and reporting laws for
      pregnant women may facilitate identifying HBV-infected pregnant women and
      preventing HBV infection in their infants.

PMID- 27866603
TI  - Effect of biosynthesized gold nanoparticles by Sargassum swartzii in alloxan
      induced diabetic rats.
AB  - Biosynthesis of gold nanoparticles (AuNPs) using Sargassum swartzii and its anti
      diabetic effect were studied using male wistar Albino rats. Formation of AuNPs
      were confirmed by UV-vis spectroscopy, Fourier transformed infrared (FTIR)
      spectroscopy, High-Resolution transmission electron microscopy (HR-TEM) and X-ray
      diffraction (XRD). Fasting blood glucose levels, serum insulin, hemoglobin and
      glycosylated hemoglobin levels in diabetic treated rats with AuNPs were
      significantly decreased compared to the control group. The results of the blood
      glucose level and serum insulin levels indicated that AuNPs could significantly
      improve the insulin resistance and glucose level in diabetic rats. AuNPs also
      shows reduction in anti-inflammation, tumor necrosis factor-alpha, interleukin-6
      and high-sensitive C-reactive protein in diabetic rats. The data showed that
      AuNPs synthesized using S. swartzii exerted antidiabetic effect, accordingly
      improve pancreas, liver and kidney damage caused by alloxan induced diabetic
      rats.

PMID- 27866604
TI  - Impact of bio-nanogold on seed germination and seedling growth in Pennisetum
      glaucum.
AB  - Nanotechnology is leading towards the development of low cost applications to
      improve the cultivation and growth of plants. The use of nanotechnology in
      agriculture will leads to a significant effect on food industry along with
      opening a new area of research in agroecosystem. In this paper gold nanoparticles
      were biosynthesized with Cassia auriculata leaf extract at room temperature and
      characterized by UV-vis spectroscopy, X-ray diffraction and transmission electron
      microscopy. The objective of this study was to investigate effect of synthesized
      bio-nanogold on an important food and biofuel producing plant Pennisetum glaucum.
      Positive effects were observed on percentage of seed germination and growth of
      seedlings. Improved germination and increased plant biomass have high economic
      importance in production of biofuel or raw materials, agriculture and
      horticulture. Although the impact of nanoparticles on plants depends on
      concentration, size and shape. The biological synthesized AuNPs can replace the
      chemically synthesized AuNPs used in gene transfer method. The study gives brief
      insight on nanoparticles effects on plants, brings attention on both positive and
      negative side of nanomaterial which can resolve phytopathological infections by
      stimulating nutrition and growth.

PMID- 27866605
TI  - Hydrothermal preparation of reduced graphene oxide-silver nanocomposite using
      Plectranthus amboinicus leaf extract and its electrochemical performance.
AB  - Graphene based nanocomposites are receiving increasing attention in many fields
      such as material chemistry, environmental science and pharmaceutical science. In
      this study, a facial synthesis of a reduced graphene oxide-silver nanocomposite
      (RGO-Ag) was carried out from Plectranthus amboinicus leaf extract. The
      synthesized nanocomposite was characterized by using X-ray diffraction, scanning
      electron microscope, Fourier transform infrared spectroscopy, X-ray photoelectron
      spectroscopy, transmission electron microscope and UV-vis spectroscopy for
      structural confirmation. The reduction of graphene oxide and silver ions was
      achieved simultaneously due to the reducibility of the Plectranthus amboinicus
      leaf extract. We further investigated the electrochemical properties of the
      biosynthesized RGO-Ag nanocomposite. A nonenzymatic H2O2 electrochemical sensor
      was shown to be successfully fabricated by using biosynthesized RGO-Ag
      nanocomposite. Moreover, the fabricated electrochemical sensor also showed good
      selectivity.

PMID- 27866607
TI  - Synthesis of silver nanoparticles by endosymbiont Pseudomonas fluorescens CA 417
      and their bactericidal activity.
AB  - The present study emphasizes on biogenic synthesis of silver nanoparticles and
      their bactericidal activity against human and phytopathogens. Nanoparticle
      synthesis was performed using endosymbiont Pseudomonas fluorescens CA 417
      inhabiting Coffea arabica L. Synthesized nanoparticles were characterized using
      hyphenated spectroscopic techniques such as UV-vis spectroscopy which revealed
      maximum absorption 425nm. Fourier transform infrared spectroscopy (FTIR) analysis
      revealed the possible functional groups mediating and stabilizing silver
      nanoparticles with predominant peaks occurring at 3346 corresponding to hydroxyl
      group, 1635 corresponding carbonyl group and 680 to aromatic group. X-ray
      diffraction (XRD) analysis revealed the Bragg's diffraction pattern with distinct
      peaks at 38 degrees  44 degrees , 64 degrees  and 78 degrees  revealing the face
      centered cubic (fcc) metallic crystal corresponding to the (111), (200), (220)
      and (311) facets of the crystal planes at 2theta angle. The energy dispersive X
      ray spectroscopy (EDS) analysis revealed presence of high intense absorption peak
      at 3keV is a typical characteristic of nano-crystalline silver which confirmed
      the presence of elemental silver. TEM analysis revealed the size of the
      nanoparticles to be in the range 5-50nm with polydisperse nature of synthesized
      nanoparticles bearing myriad shapes. The particle size determined by Dynamic
      light scattering (DLS) method revealed average size to be 20.66nm. The
      synthesized silver nanoparticles exhibited significant antibacterial activity
      against panel of test pathogens. The results showed Klebsiella pneumoniae (MTCC
      7407) and Xanthomonas campestris to be more sensitive among the test human
      pathogen and phyto-pathogen respectively. The study also reports synergistic
      effect of silver nanoparticles in combination with kanamycin which displayed
      increased fold activity up to 58.3% against Klebsiella pneumoniae (MTCC 7407).
      The results of the present investigation are promising enough and attribute
      towards growing scientific knowledge on development of new antimicrobial agents
      to combat drug resistant microorganisms. The study provides insight on emerging
      role of endophytes towards reduction of metal salts to synthesize nanoparticles.

PMID- 27866606
TI  - Effect of gemini surfactant (16-6-16) on the synthesis of silver nanoparticles: A
      facile approach for antibacterial application.
AB  - In this report, we describe the effect of Gemini surfactants1, 6-Bis (N, N
      hexadecyldimethylammonium) adipate (16-6-16) on synthesis, stability and
      antibacterial activity of silver nanoparticles (AgNPs). The stabilizing effect of
      Gemini surfactant and aggregation behavior of AgNPs was evaluated by plasmonic
      property and morphology of the AgNPs were characterized by UV-vis spectroscopy,
      Dynamic Light Scattering (DLS), X-ray diffraction (XRD), High resolution
      transmission electron microscopy (HRTEM) and Energy dispersive X-ray analysis
      (EDX) techniques. Interestingly, the formation of quite mono-dispersed spherical
      particles was found. Apart from the stabilizing role, the Gemini surfactant has
      promoted the agglomeration of individual AgNPs in small assemblies whose Plasmon
      band features differed from those of the individual nanoparticles. The
      antibacterial activity of the synthesized AgNPs on Gram-negative and Gram
      positive bacterium viz., E. coli and S. aureus was carried out by plate count,
      growth kinetics and cell viability assay. Furthermore, the mechanism of
      antibacterial activity of AgNPs was tested by Zeta potential and DLS analysis, to
      conclude that surface charge of AgNPs disrupts the cells causing cell death.

PMID- 27866608
TI  - Noble metal, oxide and chalcogenide-based nanomaterials from scalable
      phototrophic culture systems.
AB  - Phototrophic cell or tissue cultures can produce nanostructured noble metals,
      oxides and chalcogenides at ambient temperatures and pressures in an aqueous
      environment and without the need for potentially toxic solvents or the generation
      of dangerous waste products. These "green" synthesized nanobiomaterials can be
      used to fabricate biosensors and bio-reporting tools, theranostic vehicles,
      medical imaging agents, as well as tissue engineering scaffolds and biomaterials.
      While successful at the lab and experimental scales, significant barriers still
      inhibit the development of higher capacity processes. While scalability issues in
      traditional algal bioprocess engineering are well known, such as the controlled
      delivery of photons and gas-exchange, the large-scale algal synthesis of
      nanomaterials introduces additional parameters to be understood, i.e.,
      nanoparticle (NP) formation kinetics and mechanisms, biological transport of
      metal cations and the effect of environmental conditions on the final form of the
      NPs. Only after a clear understanding of the kinetics and mechanisms can the
      strain selection, photobioreactor type, medium pH and ionic strength, mean light
      intensity and other relevant parameters be specified for an optimal bioprocess.
      To this end, this mini-review will examine the current best practices and
      understanding of these phenomena to establish a path forward for this technology.

PMID- 27866609
TI  - Efficient continuous biosynthesis of silver nanoparticles by activated sludge
      micromycetes with enhanced tolerance to metal ion toxicity.
AB  - The method for producing AgNPs by granules of activated sludge micromycetes with
      enhanced tolerance to metal ion toxicity - Penicillium glabrum, Fusarium nivale
      and Fusarium oxysporum has been developed; the optimum conditions for AgNP
      biosynthesis being found: the Ag+ ion concentration, duration of the contact of
      microbial cells with silver ions, a growth phase of microorganisms, medium
      composition, a rN value, mixing conditions, and also lighting intensity. The
      effect of Cl-, SO42- and HPO42- ions binding Ag+ ions was eliminated, that
      brought to significant increase of the yield of NPs. Under batch conditions,
      silver particles of 60-110 nanometers in size were formed with a 65% yield. It
      was established that the nanoparticles were covered with microbial cell membrane
      proteins composed up to 70% by weight of the NPs that prevented their
      aggregation. In addition, it was the first time stable AgNPs had been formed by
      continuous AgNP biosynthesis by living cells of F. oxysporum with an 80% yield
      for a long time.

PMID- 27866610
TI  - In vitro anticancer activity of silver nanoparticle synthesized by Escherichia
      coli VM1 isolated from marine sediments of Ennore southeast coast of India.
AB  - In the present investigation, the bacterium Escherichia coli (VM1) was isolated
      from a marine sediments of Ennore coastal water along southeast coast of India
      was exploited for its capability of Ag NPs synthesis. The derived nanoparticles
      were characterized employing ultraviolet-visible (UV-vis) spectroscopy, Fourier
      Transform Infrared (FTIR) spectroscopy, X-ray diffraction and High Resolution
      Transmission Electron Microscopy (HRTEM) studies. The Ag NPs were further
      subjected to MTT assay to evaluate their anticancer activity against human lung
      cancer cell line (A549), human cervical cancer cell line (HeLa) and normal (Vero)
      cell line. The marine E. coli (VM1) synthesized silver nanoparticles exhibited
      considerable cytotoxic influence against human cancer cell lines, thereby
      suggesting that they have tremendous potential as effective anticancer agents.

PMID- 27866611
TI  - Facile fabrication of eco-friendly nano-mosquitocides: Biophysical
      characterization and effectiveness on neglected tropical mosquito vectors.
AB  - Mosquito (Diptera: Culicidae) vectors are solely responsible for transmitting
      important diseases such as malaria, dengue, chikungunya, Japanese encephalitis,
      lymphatic filariasis and Zika virus. Eco-friendly control tools of Culicidae
      vectors are a priority. In this study, we proposed a facile fabrication process
      of poly-disperse and stable silver nanoparticles (Ag NPs) using a cheap leaf
      extract of Ichnocarpus frutescens (Apocyanaceae). Bio-reduced Ag NPs were
      characterized by UV-vis spectrophotometry, Fourier transform infrared
      spectroscopy (FTIR), X-ray diffraction analysis (XRD), atomic force microscopy
      (AFM), scanning electron microscopy (SEM) and transmission electron microscopy
      (TEM). The acute toxicity of I. frutescens leaf extract and green-synthesized Ag
      NPs was evaluated against larvae of the malaria vector Anopheles subpictus, the
      dengue vector Aedes albopictus and the Japanese encephalitis vector Culex
      tritaeniorhynchus. Compared to the leaf aqueous extract, Ag NPs showed higher
      toxicity against A. subpictus, A. albopictus, and C. tritaeniorhynchus with LC50
      values of 14.22, 15.84 and 17.26MUg/mL, respectively. Ag NPs were found safer to
      non-target mosquito predators Anisops bouvieri, Diplonychus indicus and Gambusia
      affinis, with LC50 values ranging from 636.61 to 2098.61MUg/mL. Overall, this
      research firstly shed light on the mosquitocidal potential of I. frutescens, a
      potential bio-resource for rapid, cheap and effective synthesis of poly-disperse
      and highly stable silver nanocrystals.

PMID- 27866612
TI  - Carotenoid stabilized gold and silver nanoparticles derived from the Actinomycete
      Gordonia amicalis HS-11 as effective free radical scavengers.
AB  - The Actinomycete Gordonia amicalis HS-11 produced orange pigments when cultivated
      on n-hexadecane as the sole carbon source. When cells of this pigmented bacterium
      were incubated with 1mM chloroauric acid (HAuCl4) or silver nitrate (AgNO3), pH
      9.0, at 25 degrees C, gold and silver nanoparticles, respectively, were obtained
      in a cell associated manner. It was hypothesized that the pigments present in the
      cells may be mediating metal reduction reactions. After solvent extraction and
      High Performance Liquid Chromatography, two major pigments displaying UV-vis
      spectra characteristic of carotenoids were isolated. These were identified on the
      basis of Atmospheric Pressure Chemical Ionization Mass Spectrometry (APCI-MS) in
      the positive mode as 1'-OH-4-keto-gamma-carotene (Carotenoid K) and 1'-OH-gamma
      carotene (Carotenoid B). The hydroxyl groups present in the carotenoids were
      eliminated under alkaline conditions and provided the reducing equivalents
      necessary for synthesizing nanoparticles. Cell associated and carotenoid
      stabilized nanoparticles were characterized by different analytical techniques.
      In vitro free radical scavenging activities of cells (control, gold and silver
      nanoparticle loaded), purified carotenoids and carotenoid stabilized gold and
      silver nanoparticles were evaluated. Silver nanoparticle loaded cells and
      carotenoid stabilized silver nanoparticles exhibited improved nitric oxide (NO)
      and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activities compared to their
      control and gold counterparts. This paper thus reports cell associated
      nanoparticle synthesis by G. amicalis, describes for the first time the role of
      carotenoid pigments in metal reduction processes and demonstrates enhanced free
      radical scavenging activities of the carotenoid stabilized nanoparticles.

PMID- 27866613
TI  - A facile and green strategy for the synthesis of Au, Ag and Au-Ag alloy
      nanoparticles using aerial parts of R. hypocrateriformis extract and their
      biological evaluation.
AB  - A facile and green strategy is reported here to synthesize gold (Au), silver (Ag)
      and gold-silver (Au-Ag) alloy nanoparticles (NPs) through bio-reduction reactions
      of aqueous corresponding metal precursors mediated by extracts of aerial parts of
      R. hypocrateriformis, which act as both reducing and stabilizing agents, under
      microwave irradiation. UV-vis spectrophotometer, XRD, FT-IR, FESEM/TEM, TGA and
      EDAX analysis were used to characterize the obtained NPs. The formation of NPs is
      evident from their surface plasmon resonance peak observed at lambdamax=~550, 450
      and 500nm for Au, Ag and Au-Ag alloy NPs respectively. XRD pattern revealed that
      fcc structure, while FT-IR spectra signify the presence of phytochemicals
      adsorbed on NPs. Such a biofunctionalized NPs were characterized by their weight
      loss, 30% due to thermal degradation of plant phytochemicals observed in TG
      analysis. The spherical shape of Au, Ag and Au-Ag alloy NPs (~10-50nm) is
      observed by FE-SEM/TEM images. EDAX analysis confirms the expected elemental
      composition. Moreover, these NPs showed enhanced antimicrobial, antioxidant, and
      anticancer activities, though it is more pronounced for Au-Ag alloy NPs, which is
      due to the combining effect of phytochemicals, Au and Ag metals. Thus, the
      biosynthesized NPs could be applied as effective growth inhibitors for various
      biomedical applications.

PMID- 27866615
TI  - Anti-neoplastic selenium nanoparticles from Idiomarina sp. PR58-8.
AB  - Selenium nanoparticles (SeNPs) with novel biological activities, cancer cell
      selectivity, and low toxicity towards normal cells have gained attention for
      chemo-therapeutic and chemo-preventive applications. These nanoparticles may be
      synthesized using micro-organisms, which is the green alternative of
      nanofabrication. Here we report the intracellular synthesis of SeNPs by the
      moderate halophilic bacterium, Idiomarina sp. PR58-8 using sodium selenite as the
      precursor. Characterization of SeNPs by XRD exhibited the characteristic Bragg's
      peak of hexagonal selenium with a crystallite domain size of 34nm. Morphological
      characterization by TEM exhibited spherical nanoparticles with a size
      distribution of 150-350nm. The non-protein thiols were found to be involved in
      resistance/reduction of sodium selenite. The SeNPs exhibited selectivity in
      exerting cytotoxicity towards human cervical cancer cell line, HeLa, while being
      non-toxic towards model normal cell line, HaCaT. The SeNPs induced a caspase
      dependent apoptosis in HeLa cell lines as exhibited by the ROS assay, apoptotic
      index assay, and western blot analysis. These results suggest the application of
      SeNPs synthesized by Idiomarina sp. PR58-8 as potential anti-neoplastic agents.

PMID- 27866614
TI  - In vivo synthesis of nano-selenium by Tetrahymena thermophila SB210.
AB  - Nano-selenium has a great potential to be used in chemical, biological, medical
      and environmental fields. Biological methods for nano-selenium synthesis have
      attracted wide interests, because they can be operated at ambient temperature and
      pressure without complicated equipments. In this work, a protozoa, Tetrahymena
      thermophila (T. thermophila) SB210, was used to in vivo synthesize nano-selenium.
      The biosynthesized nano-selenium was characterized using transmission electron
      microscopy, energy dispersive X-ray spectroscopy and Raman spectroscopy. The
      synthesized amorphous spherical selenium nanoparticles had diameters of 50-500nm
      with the coexistence of irregular nano-selenium. The expressions of glutathione
      (GSH) synthesis related gene glutathione synthase, cysteine-rich protein
      metallothionein related gene metallothionein-1 and [2Fe-2S] cluster-binding
      protein related gene were up-regulated in the nano-selenium producing group.
      Also, the subsequent GSH detection and in vitro synthesis experimental results
      suggest the three proteins were likely to be involved in the nano-selenium
      synthesis process.

PMID- 27866616
TI  - In vivo synthesis of europium selenide nanoparticles and related cytotoxicity
      evaluation of human cells.
AB  - Nanotechnology strives to combine new materials for development of noble
      nanoparticles. As the nanoparticles exhibit unique optical, electronic, and
      magnetic properties depending on their composition, developing safe, cost
      effective and environmentally friendly technologies for the synthesis have become
      an important issue. In this study, in vivo synthesis of europium selenide (EuSe)
      nanoparticles was performed using recombinant Escherichia coli cells expressing
      heavy-metal binding proteins, phytochelatin synthase and metallothionein. The
      formation of EuSe nanoparticles was confirmed by using UV-vis spectroscopy,
      spectrofluorometry, X-ray diffraction, energy dispersive X-ray and transmission
      electron microscopy. The synthesized EuSe nanoparticles exhibited high
      fluorescence intensities as well as strong magnetic properties. Furthermore, anti
      cancer effect of EuSe nanoparticles against cancer cell lines was investigated.
      This strategy for the biogenic synthesis of nanoparticles has a great potential
      as bioimaging tools and drug carrying agents in biomedical fields due to its
      simplicity and nontoxicity.

PMID- 27866617
TI  - Synthesis of CdS nanoparticles from cadmium sulfate solutions using the
      extracellular polymeric substances of B. licheniformis as stabilizing agent.
AB  - Mining and hydrometallurgical industries produce large amounts of hazardous metal
      sulfate solutions as a by-product which can be recycled and exploited to produce
      valuable and advanced materials. Here, for the first time, extracellular
      polymeric substances of Bacillus licheniformis were applied as biosurfactants to
      synthesize quantum dots of cadmium sulfide from pure artificial and impure
      industrial cadmium sulfate solutions. The bacterial biopolymers stabilized the
      generated crystalline nuclei as colloidal dots and prevented their further growth
      or agglomeration. In order to discover the composition and size distribution of
      the produced particles, characterization was performed by X-ray diffraction
      (XRD), and transmission electron microscopy (TEM). Results showed that the
      particles biosynthesized from the pure solution were nano-sized cubic crystals of
      CdS with the dimensions of 2-10nm. The same product was also derived from the
      impure industrial solution. The outcomes of this study indicate the feasibility
      of cadmium or probably other metal recovery from industrial solutions and
      wastewaters in the form of valuable metal sulfide nanoparticles.

PMID- 27866618
TI  - "Use of acidophilic bacteria of the genus Acidithiobacillus to biosynthesize CdS
      fluorescent nanoparticles (quantum dots) with high tolerance to acidic pH".
AB  - The use of bacterial cells to produce fluorescent semiconductor nanoparticles
      (quantum dots, QDs) represents a green alternative with promising economic
      potential. In the present work, we report for the first time the biosynthesis of
      CdS QDs by acidophilic bacteria of the Acidithiobacillus genus. CdS QDs were
      obtained by exposing A. ferrooxidans, A. thiooxidans and A. caldus cells to
      sublethal Cd2+ concentrations in the presence of cysteine and glutathione. The
      fluorescence of cadmium-exposed cells moves from green to red with incubation
      time, a characteristic property of QDs associated with nanocrystals growth.
      Biosynthesized nanoparticles (NPs) display an absorption peak at 360nm and a
      broad emission spectra between 450 and 650nm when excited at 370nm, both
      characteristic of CdS QDs. Average sizes of 6 and 10nm were determined for green
      and red NPs, respectively. The importance of cysteine and glutathione on QDs
      biosynthesis in Acidithiobacillus was related with the generation of H2S.
      Interestingly, QDs produced by acidophilic bacteria display high tolerance to
      acidic pH. Absorbance and fluorescence properties of QDs was not affected at pH
      2.0, a condition that totally inhibits the fluorescence of QDs produced
      chemically or biosynthesized by mesophilic bacteria (stable until pH 4.5-5.0).
      Results presented here constitute the first report of the generation of QDs with
      improved properties by using extremophile microorganisms.

PMID- 27866619
TI  - Rhizopus stolonifer mediated biosynthesis of biocompatible cadmium chalcogenide
      quantum dots.
AB  - We report an efficient method to biosynthesize biocompatible cadmium telluride
      and cadmium sulphide quantum dots from the fungus Rhizopus stolonifer. The
      suspension of the quantum dots exhibited purple and greenish-blue luminescence
      respectively upon UV light illumination. Photoluminescence spectroscopy, X-ray
      diffraction, and transmission electron microscopy confirms the formation of the
      quantum dots. From the photoluminescence spectrum the emission maxima is found to
      be 424 and 476nm respectively. The X-ray diffraction of the quantum dots matches
      with results reported in literature. The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay for cell viability evaluation carried out on 3
      days transfer, inoculum 3*105 cells, embryonic fibroblast cells lines shows that
      more than 80% of the cells are viable even after 48h, indicating the
      biocompatible nature of the quantum dots. A good contrast in imaging has been
      obtained upon incorporating the quantum dots in human breast adenocarcinoma
      Michigan Cancer Foundation-7 cell lines.

PMID- 27866620
TI  - Extracellular biosynthesis of copper sulfide nanoparticles by Shewanella
      oneidensis MR-1 as a photothermal agent.
AB  - Photothermal therapy (PTT) is a minimally invasive and effective cancer treatment
      method and has a great potential for innovating the conventional chemotherapy
      approaches. Copper sulfide (CuS) exhibits photostability, low cost, and high
      absorption in near infrared region, and is recognized as an ideal candidate for
      PTT. However, CuS, as a photothermal agent, is usually synthesized with
      traditional chemical approaches, which require high temperature, additional
      stabilization and hydrophilic modification. Herein, we report, for the first
      time, the preparation of CuS nanoparticles as a photothermal agent by a
      dissimilatory metal reducing bacterium Shewanella. oneidensis MR-1. The prepared
      nanoparticles are homogenously shaped, hydrophilic, small-sized (~5nm) and highly
      stable. Furthermore, the biosynthesized CuS nanoparticles display a high
      photothermal conversion efficiency of 27.2% because of their strong absorption at
      1100nm. The CuS nanoparticles could be effectively used as a PTT agent under the
      irradiation of 1064nm. This work provides a simple, eco-friendly and cost
      effective approach for fabricating PTT agents.

PMID- 27866621
TI  - Biogenic FeS accelerates reductive dechlorination of carbon tetrachloride by
      Shewanella putrefaciens CN32.
AB  - Dissimilatory metal reducing bacteria (DMRB) widely exist in the subsurface
      environment and are involved in various contaminant degradation and element
      geochemical cycling processes. Recent studies suggest that DMRB can biosynthesize
      metal nanoparticles during metal reduction, but it is unclear yet how such
      biogenic nanomaterials would affect their decontamination behaviors. In this
      study, we found that the dechlorination rates of carbon tetrachloride (CT) by
      Shewanella putrefaciens CN32 was significantly increased by 8 times with the
      formation of biogenic ferrous sulfide (FeS) nanoparticles. The pasteurized
      biogenic FeS enabled 5 times faster dechlorination than abiotic FeS that had
      larger sizes and irregular structure, confirming a significant contribution of
      the biogenic FeS to CT bioreduction resulting from its good dispersion and
      relatively high dechlorination activity. This study highlights a potentially
      important role of biosynthesized nanoparticles in environmental bioremediation.

PMID- 27866622
TI  - Palladium nanoparticles enzyme aggregate (PANEA) as efficient catalyst for Suzuki
      Miyaura reaction in aqueous media.
AB  - Palladium nanoparticles enzyme aggregate (PANEA) were prepared from Candida
      antarctica B lipase and palladium salt by precipitation and subsequent in situ Pd
      nanoparticle formation. This heterogeneous catalyst was successfully used for the
      Suzuki-Miyaura cross-coupling reaction between bromobenzene with different
      phenylboronic acid derivatives under mild reaction conditions and using low Pd
      amount. The nanocatalyst exhibited the highest catalytic activity in a mixture of
      methanol/water (1:1), obtaining good to excellent product yields from the cross
      coupling reaction. A variety of functional groups were accepted and the catalyst
      was recycled 4 times without activity loss.

PMID- 27866623
TI  - Biophysical characterization and activity analysis of nano-magnesium supplemented
      cellulase obtained from a psychrobacterium following graphene oxide
      immobilization.
AB  - Cellulase enzyme was purified from a psychrophilic strain of Bacillus subtilis
      obtained from east Himalayan mountains. The native enzyme showed optimum activity
      at 15 degrees C and pH 8.0.The Magnesium oxide nanoparticle (MgN) supplemented
      enzyme when immobilized on graphene oxide nanosupport (GO), via glutaraldehyde as
      cross linker, showed 2.98 folds increase in enzymatic activity at 8 degrees C and
      more than 3.5 folds activity increment at 90 degrees C. The MgN-cel on graphene
      (GO-MgN-cel) showed a decrease in Km by 6.7 folds at 8 degrees C and 34 folds at
      90 degrees C. GO-MgN-cel showed 5 fold and 4.7 fold increase in Vmax at 8 degrees
      C and 90 degrees C respectively than the untreated enzyme.When compared to native
      enzyme, GO-MgN-cel had t1/2 (half life) and Ed increased by 72.5 fold and 2.48
      fold respectively at 90 degrees C; and 41.6 fold and 2.19 fold respectively at 8
      degrees C. Enzymatic activity of GO-MgN-cel was retained even after 12 repeated
      uses and showed storage stability at 4 degrees C for more than 120days. This
      nanoparticle assisted immobilization technique can be utilized in bioprocessing
      industries which require functioning at these extreme ranges of temperature.

PMID- 27866624
TI  - A review on the biosynthesis of metallic nanoparticles (gold and silver) using
      bio-components of microalgae: Formation mechanism and applications.
AB  - The synthesis of nanoparticles (NP) using algae has been underexploited and even
      unexplored. In recent times, there are few reports on the synthesis of NP using
      algae, which are being used as a bio-factory for the synthesis. Moreover, the
      algae are a renewable source, so that it could be effectively explored in the
      green synthesis of NP. Hence, this review reports on the biosynthesis of NP
      especially gold and silver NP using algae. The most widely reported NP from algae
      are silver and gold than any other metallic NP, which might be due to their
      enormous biomedical field applications. The NP synthesized by this method is
      mainly in spherical shape; the reports are revealing the fact that the cell free
      extracts are highly exploited for the synthesis than the biomass, which is
      associated with the problem of recovering the particles. Besides, mechanism
      involving in the reduction and stabilization is well demonstrated to deepen the
      knowledge towards enhancement possibilities for the synthesis and applications.

PMID- 27866625
TI  - Biological synthesis of nanoparticles in biofilms.
AB  - The biological synthesis of nanoparticles (NPs) by bacteria and biofilms via
      extracellular redox reactions has received attention because of the minimization
      of harmful chemicals, low cost, and ease of culturing and downstream processing.
      Bioreduction mechanisms vary across bacteria and growth conditions, which leads
      to various sizes and shapes of biosynthesized NPs. NP synthesis in biofilms
      offers additional advantages, such as higher biomass concentrations and larger
      surface areas, which can lead to more efficient and scalable biosynthesis.
      Although biofilms have been used to produce NPs, the mechanistic details of NP
      formation are not well understood. In this review, we identify three critical
      areas of research and development needed to advance our understanding of NP
      production by biofilms: 1) synthesis, 2) mechanism and 3) stabilization.
      Advancement in these areas could result in the biosynthesis of NPs that are
      suitable for practical applications, especially in drug delivery and
      biocatalysis. Specifically, the current status of methods and mechanisms of
      nanoparticle synthesis and surface stabilization using planktonic bacteria and
      biofilms is discussed. We conclude that the use of biofilms to synthesize and
      stabilize NPs is underappreciated and could provide a new direction in biofilm
      based NP production.

PMID- 27866626
TI  - Seaweeds: A resource for marine bionanotechnology.
AB  - Marine bionanotechnology is one of the most promising areas of research in modern
      science and technology. Although there are multitude methods for the synthesis of
      nanoparticles (NPs), there is an increasing attention in developing high-yield,
      low-cost, non-toxic and eco-friendly procedures. The vital advantages of greener
      synthesis are cost-effective, reduced usage of toxic chemicals and abundant
      availability of resources. During the last ten years, there have been many
      biological entities used to elevate novel, greener and affordable methods for the
      metal NPs synthesis. Rate of synthesis and stability are higher for plant
      material mediated NPs. However, in comparison with terrestrial resources, marine
      resources have not been fully explored for synthesis of noble metal NPs. Our
      present review is designed to speculate the importance of usage of vast marine
      resources and its mediated NPs synthesis, in particular seaweed-mediated NPs
      synthesis to overcome the limitations involved in physical and chemical methods.
      Finally, recent advancements in greener synthesis of metal NPs, their size,
      distribution, morphology and applications such as antimicrobial, antifouling and
      anticancer potentials are briefly described along with portraying the prospective
      scope of research in this field without any negative impact on the environment.

PMID- 27866627
TI  - Green synthesized nanoparticles in the fight against mosquito-borne diseases and
      cancer-a brief review.
AB  - Nanobiomedicine and parasitology are facing a number of key challenges, which
      mostly deal with the paucity of effective preventive and curative tools against
      mosquito-borne diseases and cancer. In this scenario, the employ of botanical and
      invertebrate extracts as reducing, stabilizing and capping agents for the
      synthesis of nanoparticles is advantageous over chemical and physical methods,
      since it is one-pot, cheap, and does not require high pressure, energy,
      temperature, or the use of highly toxic chemicals. Considering the overlooked
      connection between mosquito vector activity and the spread of cancer in USA, this
      review focused on the current knowledge available about green synthesized
      nanoparticles with efficacy against mosquito-borne diseases and cancer. Green
      fabricated metal nanoparticles showed antiplasmodial activity that often
      encompasses the efficacy of currently marked drugs for malaria treatment. They
      have been also reported as growth inhibitors against dengue virus (serotype DEN
      2), with moderate cytotoxicity on mammalian cells. However, this feature is
      strongly dependent to the botanical agents employed during nanosynthesis. In
      addition, green nanoparticles have been successfully used to reduce mosquito
      young instar populations in the field. The final section focuses on some issues
      for future research, with special reference to the chemical standardization of
      the botanical extracts used for nanosynthesis and the potential effects on green
      fabricated nanoparticles on non-target organisms.

PMID- 27866628
TI  - Production of gold nanoparticles by electrode-respiring Geobacter sulfurreducens
      biofilms.
AB  - The goal of this work was to synthesize gold nanoparticles (AuNPs) using
      electrode-respiring Geobacter sulfurreducens biofilms. We found that AuNPs are
      generated in the extracellular matrix of Geobacter biofilms and have an average
      particle size of 20nm. The formation of AuNPs was verified using TEM, FTIR and
      EDX. We also found that the extracellular substances extracted from electrode
      respiring G. sulfurreducens biofilms reduce Au3+ to AuNPs. From FTIR spectra, it
      appears that reduced sugars were involved in the bioreduction and synthesis of
      AuNPs and that amine groups acted as the major biomolecules involved in binding.

PMID- 27866629
TI  - Fungal surface protein mediated one-pot synthesis of stable and hemocompatible
      gold nanoparticles.
AB  - Despite their large secretome and wide applications in bioprocesses, fungi remain
      underexplored in metal nanoparticles (MNP) biosynthesis. Previous studies have
      shown that cell surface proteins of Rhizopus oryzae play a crucial role in
      biomineralization of Au(III) to produce gold nanoparticles (AuNPs). Therefore, it
      is hypothesized that purified cell surface protein may produce in vitro AuNPs
      with narrow size distribution for biomedical and biocatalytic applications.
      However, different protein extraction methods might affect protein stability and
      the AuNP biosynthesis process. Herein, we have explored the extraction of cell
      surface proteins from R. oryzae using common detergents and reducing agent
      (sodium dodecyl sulfate (SDS) Triton X-100, and 1,4-dithiothreitol (DTT)) and
      their effect on the size and shape of the biosynthetic AuNPs. The surface
      proteins extracted with reducing agent (DTT) and non-ionic detergent (Triton X
      100) produce spherical AuNPs with a mean particle size of 16+/-7nm, and 19+/-4nm,
      respectively, while the AuNPs produced by the surface protein extracted by ionic
      detergent (SDS) are flower-like AuNPs with broader size distribution of 43+/
      19nm. This synthetic approach does not require use of any harsh chemicals,
      multistep preparation and separation process, favouring environmental
      sustainability. The biosynthetic AuNPs thus formed, are stable in different
      physiological buffers and hemocompatible, making them suitable for biomedical
      applications.

PMID- 27866630
TI  - Intracellular synthesis of gold nanoparticles with antioxidant activity by
      probiotic Lactobacillus kimchicus DCY51T isolated from Korean kimchi.
AB  - A straightforward synthesis of gold nanoparticles (AuNps) is achieved by novel
      probiotic Lactobacillus kimchicus DCY51T isolated from Korean kimchi via an
      intracellular membrane-bound mechanism. The bioreduction of HAuCl4 into AuNps was
      verified by ultraviolet-visible spectrophotometry at ~540nm. AuNps were spherical
      with varying sizes of 5-30nm. AuNps maintained an average crystallite size of
      13nm and demonstrated long-term stability in physiological buffer and biological
      media. Furthermore, the protective capping layer consisted of amino acid residues
      and surface-bound proteins rendered them non-toxic to murine macrophage
      (RAW264.7) and human colorectal adenocarcinoma (HT29) cell lines. Finally,
      biosynthesized AuNps served as superior free radical scavengers against 2,2
      diphenyl-1-picrylhydrazyl (DPPH) in contrast to their corresponding gold salt. In
      short, this green synthesis is cost-effective and advantageous for the
      development of a new class of probiotics mediated and non-toxic carriers in
      targeted drug delivery systems, cancer diagnostic, photothermal therapy,
      biosensing, and medical imaging.

PMID- 27866633
TI  - Anti-PD-1 Antibody Treatment and the Development of Acute Pulmonary Tuberculosis.

PMID- 27866632
TI  - Predicting Malignant Nodules from Screening CTs.

PMID- 27866631
TI  - Rapid detection of viral antibodies based on multifunctional Staphylococcus
      aureus nanobioprobes.
AB  - Biosynthesis of nanoparticles inside S. aureus cells has enhanced the sensitivity
      of immunoassays based on the S. aureus nanoparticles. However, the current
      methods are limited to antigen detection by conjugating IgG antibodies on S.
      aureus nanoparticles. In this study, a simple way to conjugate antigens to the S.
      aureus nanobioparticles was developed by utilizing a cell wall binding domain
      (CBD) from a bacteriophage lysin PlyV12. Based on this novel design, simple
      agglutination tests of the IgG antibodies of Ebola virus (EBOV) nucleoprotein
      (NP) and Middle East Respiratory Virus (MERS) NP in rabbit sera were successfully
      developed by conjugating the S. aureus nanobioparticles with two fusion proteins
      EBOV NP- CBD and MERS NP-CBD, respectively. The conjugation was done easily by
      just mixing the fusion proteins with the S. aureus nanoparticles. The detection
      time was within 20 min without any special equipment or expertise. As far as we
      know, this is the first time to realize the detection of viral antibodies based
      on S. aureus nanoparticles.

PMID- 27866634
TI  - Transient Asymptomatic Pulmonary Opacities during Osimertinib Treatment: "Stop or
      Go" Decision.

PMID- 27866635
TI  - Prophylactic Cranial Irradiation for Extensive-Stage Small Cell Lung Cancer.

PMID- 27866636
TI  - Prophylactic Cranial Irradiation for Extensive-Stage Small Cell Lung Cancer:
      Authors' Reply.

PMID- 27866637
TI  - Are All ALK Inhibitors Really Necessary?

PMID- 27866638
TI  - Sequential Use of ALK Inhibitors: An Optional Approach.

PMID- 27866639
TI  - Innovation within a university setting.
AB  - Elisabeth K. Wynne, MD, completed her undergraduate degree in bioengineering and
      is currently a surgical resident in training at the University of Washington.
      From 2014-2016, she served as a Biodesign Fellow at Stanford University. She
      plans to pursue a career of innovation as an academic surgeon. Thomas M. Krummel,
      MD, is the Emile Holman Professor and Chair Emeritus of the Department of Surgery
      at Stanford University School of Medicine. Throughout his career, Dr Krummel has
      been a pioneer and an innovator. For >12 years, he has partnered with Dr Paul
      Yock to co-direct the Stanford Biodesign program, which is designed to teach
      innovation at the emerging frontiers of engineering and biomedical sciences. Dr
      Krummel is Chairman of the Fogarty Institute for Innovation Board of Directors,
      and President of the International Scientific Committee at Institut de Recherche
      contre les Cancers de l'Appareil Digestif - IRCAD at the University of Strasbourg
      and is a frequent consultant to the medical device industry.

PMID- 27866640
TI  - Innovation in rural settings.

PMID- 27866641
TI  - Optimizing the success of surgeons innovating and commercializing ideas: 10
      lessons learned.
AB  - Michael Blackhurst is a salaried employee in the role of General Manager of the
      Surgical Product Group of Fisher and Paykel Healthcare Limited.

PMID- 27866643
TI  - Evaluating levels of dentist participation in Medicaid: A complicated endeavor.
AB  - BACKGROUND: The availability of dentists to care for Medicaid beneficiaries is a
      longstanding concern of many families and those who serve them in the dental
      profession as well as policy makers. Yet, little information beyond the number of
      enrolled dentists has been reliably determined. The American Dental Association
      (ADA) Health Policy Institute has called for more nuanced measures that better
      reflect dentistry's contribution to the care of Medicaid beneficiaries. METHODS:
      The authors calculated percentages of general and pediatric dentists who enrolled
      in Medicaid, billed Medicaid, and treated Medicaid beneficiaries in each state
      for which data were available from the ADA's 2008 study, the Association of State
      and Territorial Dental Directors' 2013 report, and the 2013 federal Web site
      InsureKidsNow.org. To determine the number of primary dentists available to treat
      Medicaid beneficiaries, the ADA masterfile list of clinically active dentists was
      adjusted to remove nonpediatric dental specialists. RESULTS: The authors
      determined that the ADA's 2015 analysis of dentists enrolled in Medicaid was the
      most rigorously assessed source for enrollment but did not report numbers of
      billing or treating dentists. Increasingly stringent metrics of participation are
      associated with considerable declines in dentist participation. They found the
      underlying data sources unreliable, inaccurate, and incomparable within and among
      states. CONCLUSIONS: The authors concluded that no consistent, comparable,
      ongoing source of dentist participation in Medicaid exists that reliably provides
      substantive information to the profession and policy makers. PRACTICAL
      IMPLICATIONS: Dentistry's ability to respond to policymakers' concerns about
      service to Medicaid beneficiaries depends on the development and implementation
      of a standardized, reliable, systematic, and ongoing method to measure meaningful
      participation.

PMID- 27866642
TI  - Genetic susceptibility to Gilbert's syndrome in a valencian population; efficacy
      of the fasting test.
AB  - OBJECTIVE: To describe the populational distribution of the UGT1A1*28 variant
      (genetic variant code rs8175347) located in the promotor of the UGT gene and
      correlate its genotypes with the results of the fasting test, as well as its
      relationship with the biochemical disorder of Gilbert's syndrome (GS) in a
      Valencian population. PATIENTS AND METHODS: We studied the prevalence of the
      genotypes (TA)6/6 (TA)6/7 and (TA)7/7 of the deleterious variant rs8175347 in 144
      patients with hyperbilirubinemia, 38 of whom had previously undergone the fasting
      test to diagnose GS, and in 150 control patients. By analysing the genomic region
      of the TATA box of the UGT1A1 gene promotor using Sanger sequencing, we
      established the correlation between the rs8175347 genotypes and the fasting test
      results and with the patients' biochemical disorders. RESULTS: The rate of
      heterozygosity of allele (TA)7 in the control population was 32% and increased to
      87.59% among the patients with suspected GS. The rate of genotype TA7/7 was
      81.94% among the patients with hyperbilirubinemia, compared with 11.33% in the
      control patients. The fasting test showed a 15.79% rate of false negatives and a
      5.26% rate of false positives. CONCLUSIONS: The high frequency of allele (TA)7
      among the Valencian control population, almost double the 5% reported for
      European control patients, confirms the high rate of GS reported in the Spanish
      population, without observing significant differences between the geographical
      ends of the country. The efficacy and reliability of the fasting test for the
      diagnosis of GS is questionable.

PMID- 27866644
TI  - China-leading the way in diabetes research.

PMID- 27866645
TI  - Reply.

PMID- 27866646
TI  - A Prospective Study of Biometric Stability After Scleral Buckling Surgery.

PMID- 27866647
TI  - The Maastricht-Duke bridge: An era of mentoring in clinical research - A model
      for mentoring in clinical research - A tribute to Dr. Galen Wagner.
AB  - OBJECTIVE: With the passing of Dr. Galen Wagner, an exceptional collaboration
      between Maastricht University Medical Center, The Netherlands, and Duke Clinical
      Research Institute, USA, has come to an end. This article focuses on the
      background of what Galen coined the Maastricht-Duke bridge (MD-bridge), its
      merits, limitations and development throughout the years, and his special role.
      METHODS: Between 2004 and 2015, 23 Maastricht University medical students and
      post-graduate students were enrolled in the 4-month research elective, mentored
      by Galen and the Maastricht co-mentor. They were asked to complete a survey about
      their MD-bridge experience. RESULTS: Sixteen out of the 23 students responded.
      None but 1 participant had prior research experience. Following their MD bridge
      program most participants published 1 or more manuscripts and/or presented their
      research in an international setting. They felt they had full responsibility as a
      leader of their project with all participants developing meaningful skills useful
      in their current job. Fourteen out of 16 would recommend the MD-bridge experience
      to others. Participants considered the program of great value for their personal
      growth and independence, giving a feeling of achievement. In addition, for some
      participants it led to careers in foreign countries including medical practice
      and research, or obtaining PhDs. CONCLUSIONS: With Galen's impressive career of
      mentoring students, including the 23 MD-bridge participants, he has left behind
      an amazing concept of self-development in research and personal life. The
      successes of the MD-bridge prove that it is possible for students to be young
      investigators during or just after medical school with the potential to
      contribute to developing meaningful skills and noteworthy careers. Collaborations
      between international universities, such as the MD-bridge, are feasible and
      should be embraced by other institutions.

PMID- 27866648
TI  - Extracorporeal life support is safe in trauma patients.
AB  - INTRODUCTION: The role of extracorporeal life support (ECLS) in the critically
      ill trauma patient is poorly defined, possibly leading to the underutilization of
      this lifesaving therapy in this population. This study examined survival rates
      and risk factors for death in trauma patients who received ECLS. METHODS: Data
      from the National Trauma Data Bank was retrospectively reviewed to identify
      trauma patients who received ECLS from January 2012 to December 2014. Clinical
      outcomes and risk factors for death were examined in these patients. RESULTS:
      Eighty patients were identified and included in the final analysis. Overall
      survival to hospital discharge was 64%. Survivors and non-survivors were similar
      in regard to age, gender, weight, and injury mechanism. Non-survivors had greater
      median injury severity scores (ISS) (29 non-survivors vs. 24 survivors, p=0.018)
      and had a shorter median total hospital length of stay (8days non-survivors vs.
      32days survivors, p<0.001). Analysis of specific anatomic locations of traumatic
      injury, including serious head/neck, thoracic, and abdominal injuries, revealed
      no impact on patient survival. Multivariable logistic regression analysis
      identified increasing age and ISS as significant risk factors for mortality;
      whereas treatment at facilities that performed multiple ECLS runs over the study
      period was associated with improved survival. CONCLUSIONS: Extracorporeal life
      support appears to be an effective treatment option in trauma patients with
      severe cardiopulmonary failure. Survival in trauma patients receiving ECLS is
      similar to that observed in the general ECLS population and this may represent an
      underutilized therapy in this population.

PMID- 27866649
TI  - Management of paediatric splenic injury in the New South Wales trauma system.
AB  - : Since the 1980's, paediatric surgeons have increasingly managed blunt splenic
      injury (BSI) in children non-operatively. However, studies in North America have
      shown higher operation rates in non-paediatric centres and by adult surgeons.
      This association has not been examined elsewhere. OBJECTIVE: To investigate the
      management of BSI in New South Wales (NSW) children, to determine the patient and
      hospital factors related to the odds of operation. Secondarily, to investigate
      whether the likelihood of operation varied by year. METHODS: Children age 0-16
      admitted to a NSW hospital between July 2000 and December 2011 with a diagnosis
      of BSI were identified in the NSW Admitted Patient Data Collection, and linked to
      deaths data from Registry of Births Deaths and Marriages, and Bureau of
      Statistics. The operation rate was calculated and compared between different
      hospital types. Univariable analysis was used to determine patient and hospital
      factors associated with operative management. The difference in the odds of
      operation between the oldest data (July 2000-December 2005) and most recent
      (January 2006-December 2011) was also examined. Multivariable logistic regression
      with stepwise elimination was then performed to determine likelihood of operative
      management according to hospital category and era, adjusting for potential
      confounders. RESULTS: 955 cases were identified, with 101(10.6%) managed
      operatively. On multivariable analysis, factors associated with operation
      included age (OR 1.11, 95% CI 1.01-1.18, p<0.05), massive splenic disruption (OR
      3.10, 95% CI 1.61-6.19, p<0.001), hollow viscus injury (OR 11.03, 95% CI 3.46
      34.28, p<0.001) and transfusion (OR 7.70, 95% CI 4.54-13.16, p<0.001). Management
      outside a paediatric trauma centre remained significantly associated with
      operation, whether it be metropolitan adult trauma centre (OR 4.22 95% CI 1.70
      10.52, p<0.01), rural trauma centre (OR 3.72 95% CI 1.83-7.83, p<0.001) or
      metropolitan local hospital (OR 5.23, 95% CI 1.22-18.93 p<0.05). Comparing the 2
      eras, the overall operation rate fell, although not significantly, from 12.9% to
      8.7% (OR 1.3, 95% CI 0.89-243 p=0.13) CONCLUSION: While Paediatric Surgeons have
      wholeheartedly adopted non-operative management, away from paediatric centres,
      children in NSW are still being operated on for BSI unnecessarily. While the
      factors at play may be complex, further evaluation of the management and movement
      of injured children within the broad NSW trauma system is required.

PMID- 27866650
TI  - Evidence-Based and Personalized Medicine. It's [AND] not [OR].
AB  - Good clinical practice is an amalgamation of personalized medicine with evidence
      based medicine in the best interests of patient. Hence, our title uses Boolean
      operators to indicate that it is [AND] not [OR]. This is the syntax of formal
      searching for systematic reviews, ensuring that all the evidence is found.
      Comprehensive evidence-based guidance can thus be formulated. Many residents and
      fellows around the world, and their chiefs, are now exposed to consensus
      documents, white papers, levels of appropriateness, and guidelines and are in
      many jurisdictions expected to comply with them. However, they are the summation
      of many forms of evidence, each of which has its place, and we consider them in
      turn in this article.

PMID- 27866651
TI  - Cardiac Surgery in Patients With Previous Hepatic or Renal Transplantation: A
      Pair-Matched Study.
AB  - BACKGROUND: The objective of this study was to compare outcomes of patients with
      previous solid organ transplant with those of a pair-matched population. METHODS:
      Data from our prospectively maintained cardiac surgery registry were obtained and
      identified 70 transplant recipients (21 hepatic, 49 renal) who were operated on
      at our department of cardiac surgery between 2000 and 2013; they formed the
      transplant group. Those patients were pair-matched regarding age, sex, and
      cardinal cardiac risk factors to form the pair-matched group. RESULTS: Early
      mortality was 15.7% in the transplant group (23.8% hepatic, 12.2% renal allograft
      recipients) versus 5.7% in the pair-matched population. The overall mortality was
      32.9% in the transplant group (38.1% hepatic, 30.6% renal allograft recipients)
      versus 11.4% in the pair-matched group (p < 0.01) over a median follow-up of 32
      months. Transplant patients had more bleeding complications (12.9%) than the pair
      matched patients (1.4%), and more operative reexploration (15.7% versus 2.9%),
      atrial fibrillation (32.9% versus 10.0%), new-onset dialysis (17.1% versus 5.7%),
      and sepsis (10.0% versus 1.4%). One-, 2-, 5-, and 10-year survival for the
      transplant group versus the pair-matched group, respectively, was 74%, 71%, 66%,
      and 56% versus 93%, 91%, 88%, 81%. Multivariate predictors of mortality were
      solid organ transplant (hazard ratio 3.8, 95% confidence interval: 1.6 to 9.2),
      intraoperative transfusion (hazard ratio 1, 95% confidence interval: 1.00 to
      1.01), and postoperative increase in bilirubin concentration (hazard ratio 1.34,
      95% confidence interval: 1.08 to 1.65). CONCLUSIONS: Cardiac surgery is feasible
      for recipients of solid organ transplants with acceptable early morbidity and
      mortality.

PMID- 27866652
TI  - Tortuosity, Recurrent Segments, and Bridging of the Epicardial Coronary Arteries
      in Patients With the Takotsubo Syndrome.
AB  - Myocardial bridging (MB) and a long recurrent wraparound left anterior descending
      artery (wrap-LAD) are coronary anatomic variants that have been recently
      suggested to be associated with takotsubo syndrome (TS). Until now, coronary
      artery tortuosity (CAT) has never been investigated in this setting. Our study
      sought to evaluate the prevalence of the aforementioned anatomic variants in a
      large population with TS. In this retrospective angiographic study, 109 patients
      with TS were compared with 109 age- and gender-matched subjects without coronary
      artery disease, valve heart disease, or cardiomyopathy. CAT was identified by >=3
      consecutive curvatures >=90 degrees  (criteria 1) or by >=2 consecutive
      curvatures >=180 degrees  (criteria 2). Wrap-LAD was defined if any part of the
      vessel outreached the apex of the left ventricle and MB as the presence of a
      milking effect or a step-up and step-down phenomenon. An anatomic variant was
      found in 79 patients with TS (72%) and in 48 controls (44%) (p <0.001). CAT in at
      least 1 vessel (criteria 1: 49% vs 20%, p <0.001; criteria 2: 38% vs 13%, p
      <0.001), >=2 vessels (criteria 2: 14% vs 3%, p = 0.005), and wrap-LAD (41% vs
      27%, p = 0.02) were significantly more frequent in patients with TS than in
      controls. The prevalence of MB (9% vs 5%, p = 0.18) did not differ between
      groups. In conclusion, CAT and wrap-LAD have higher prevalence in patients with
      TS than in matched controls. These findings could support the hypothesis that
      anatomic variants might act as potential pathogenic substrates in TS.

PMID- 27866653
TI  - Thoralf Mauritz Sundt III, MD: A Conversation With the Editor.

PMID- 27866655
TI  - Prediction of Cardiovascular Mortality by Estimated Cardiorespiratory Fitness
      Independent of Traditional Risk Factors: The HUNT Study.
AB  - OBJECTIVE: To assess the predictive value of estimated cardiorespiratory fitness
      (eCRF) and evaluate the additional contribution of traditional risk factors in
      cardiovascular disease (CVD) mortality prediction. PARTICIPANTS AND METHODS: The
      study included healthy men (n=18,721) and women (n=19,759) aged 30 to 74 years. A
      nonexercise algorithm estimated cardiorespiratory fitness. Cox proportional
      hazards models evaluated the primary (CVD mortality) and secondary (all-cause,
      ischemic heart disease, and stroke mortality) end points. The added predictive
      value of traditional CVD risk factors was evaluated using the Harrell C statistic
      and net reclassification improvement. RESULTS: After a median follow-up of 16.3
      years (range, 0.04-17.4 years), there were 3863 deaths, including 1133 deaths
      from CVD (734 men and 399 women). Low eCRF was a strong predictor of CVD and all
      cause mortality after adjusting for established risk factors. The C statistics
      for eCRF and CVD mortality were 0.848 (95% CI, 0.836-0.861) and 0.878 (95% CI,
      0.862-0.894) for men and women, respectively, increasing to 0.851 (95% CI, 0.839
      0.863) and 0.881 (95% CI, 0.865-0.897), respectively, when adding clinical
      variables. By adding clinical variables to eCRF, the net reclassification
      improvement of CVD mortality was 0.014 (95% CI, -0.023 to 0.051) and 0.052 (95%
      CI, -0.023 to 0.127) in men and women, respectively. CONCLUSION: Low eCRF is
      independently associated with CVD and all-cause mortality. The inclusion of
      traditional clinical CVD risk factors added little to risk discrimination and did
      not improve the classification of risk beyond this simple eCRF measurement, which
      may be proposed as a practical and cost-effective first-line approach in primary
      prevention settings.

PMID- 27866658
TI  - Effect of Modulated Electrohyperthermia on the Pharmacokinetics of Oral
      Transmucosal Fentanyl Citrate in Healthy Volunteers.
AB  - PURPOSE: This study aimed to determine whether changes occur in fentanyl
      absorption and disposition when administered in conjunction with modulated
      electrohyperthermia (mEHT) treatment. METHODS: A randomized, single-dose,
      crossover, open-label study was used to investigate the effect of mEHT on the
      pharmacokinetic properties of fentanyl in 12 healthy volunteers. The 12 healthy
      volunteers were each administered a single dose of oral transmucosal fentanyl
      citrate (OTFC) or a single dose of OTFC with mEHT. mEHT was performed on the
      abdomen for 1 hour. Blood samples were collected for 24 hours after dosing. The
      temperature of the abdominal skin surface was assessed before dosing and at 10,
      20, and 60 minutes after dosing. FINDINGS: Geometric mean ratios (ratio of
      fentanyl with mEHT to fentanyl alone) for the Cmax and AUC0-last were 1.20 (90%
      CI, 1.09-1.32) and 1.15 (90% CI, 0.99-1.33), respectively. The mean temperature
      of the abdominal skin surface increased by approximately 4 degrees C.
      IMPLICATIONS: There was an increase in the overall exposure to the drug without
      implications of any clinical significance. OTFC can be administered without
      limitations in combination with mEHT, and it is not necessary to modify the
      dosing regimen. cris.nih.go,kr Identifier: KCT0001286.

PMID- 27866656
TI  - An analysis of possible off target effects following CAS9/CRISPR targeted
      deletions of neuropeptide gene enhancers from the mouse genome.
AB  - We have successfully used comparative genomics to identify putative regulatory
      elements within the human genome that contribute to the tissue specific
      expression of neuropeptides such as galanin and receptors such as CB1. However, a
      previous inability to rapidly delete these elements from the mouse genome has
      prevented optimal assessment of their function in-vivo. This has been solved
      using CAS9/CRISPR genome editing technology which uses a bacterial endonuclease
      called CAS9 that, in combination with specifically designed guide RNA (gRNA)
      molecules, cuts specific regions of the mouse genome. However, reports of "off
      target" effects, whereby the CAS9 endonuclease is able to cut sites other than
      those targeted, limits the appeal of this technology. We used cytoplasmic
      microinjection of gRNA and CAS9 mRNA into 1-cell mouse embryos to rapidly
      generate enhancer knockout mouse lines. The current study describes our analysis
      of the genomes of these enhancer knockout lines to detect possible off-target
      effects. Bioinformatic analysis was used to identify the most likely putative off
      target sites and to design PCR primers that would amplify these sequences from
      genomic DNA of founder enhancer deletion mouse lines. Amplified DNA was then
      sequenced and blasted against the mouse genome sequence to detect off-target
      effects. Using this approach we were unable to detect any evidence of off-target
      effects in the genomes of three founder lines using any of the four gRNAs used in
      the analysis. This study suggests that the problem of off-target effects in
      transgenic mice have been exaggerated and that CAS9/CRISPR represents a highly
      effective and accurate method of deleting putative neuropeptide gene enhancer
      sequences from the mouse genome.

PMID- 27866657
TI  - Distribution and chemical coding of sensory neurons innervating the skin of the
      porcine hindlimb.
AB  - The aim of the present study was to establish the origin and chemical phenotyping
      of neurons involved in skin innervation of the porcine hind leg. The dorsal root
      ganglia (DRGs) of the lumbar (L4-L6) and sacral (S1-S3) spinal nerves were
      visualized using the fluorescent tracer Fast Blue (FB). The morphometric analysis
      of FB-positive (FB+)neurons showed that in the L4, L5, S1 and S2 DRGs, the small
      sized perikarya constituted the major population, whereas in the L6 and S3 DRGs
      the medium-sized cells made up the major population. In all these ganglia, large
      sized FB+ perikarya constituted only a small percentage of all FB+ neurons.
      Immunohistochemistry revealed that small- and medium-sized FB+ perikarya
      contained sensory markers such as: substance P (SP), calcitonin gene related
      peptide (CGRP) and galanin (GAL); as well as various other factors such as
      somatostatin (SOM), calbindin-D28k (CB), pituitary adenylate cyclase-activating
      polypeptide (PACAP) and neuronal nitric oxide synthase (nNOS). Meanwhile large
      sized FB+ perikarya usually expressed SP, CGRP or PACAP. In the lumbar DRGs, some
      large cells also contained SOM and CB. Double-labeling immunohistochemistry
      showed that SP-positive neurons co-expressed CGRP, GAL or PACAP; while PACAP
      positive cells co-expressed GAL or nNOS. Neurons stained for SOM were also
      immunoreactive for CB or GAL, while neurons stained for nNOS were also
      immunoreactive for GAL. In conclusion, the present data has indicated that the
      distribution and chemical phenotyping of the porcine skin-projecting neurons are
      different within DRGs of the lumbar (forming a femoral nerve) and sacral (forming
      a sciatic nerve) spinal nerves.

PMID- 27866654
TI  - CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes.
AB  - The CRISPR-Cas9 RNA-guided DNA endonuclease has contributed to an explosion of
      advances in the life sciences that have grown from the ability to edit genomes
      within living cells. In this Review, we summarize CRISPR-based technologies that
      enable mammalian genome editing and their various applications. We describe
      recent developments that extend the generality, DNA specificity, product
      selectivity, and fundamental capabilities of natural CRISPR systems, and we
      highlight some of the remarkable advancements in basic research, biotechnology,
      and therapeutics science that these developments have facilitated.

PMID- 27866659
TI  - Value of Propensity Score Matching for Equalizing Comparator Groups in
      Observational Database Studies: A Case Study in Anti-infectives.
AB  - PURPOSE: Propensity score methodologies can reduce bias and confounding in
      nonrandomized studies, including pharmaceutical comparative effectiveness
      studies. An observational case study was developed to demonstrate the impact of
      propensity score adjustments on outcomes (ie, discharge status) of patients
      hospitalized for complicated intra-abdominal infections. METHODS: Two cohorts
      were examined: intensive care unit (ICU) (vs non-ICU) patients and tigecycline
      treated patients (vs patients receiving other antibiotics). Discharge status was
      captured before propensity scoring. FINDINGS: The impact of propensity scoring on
      discharge outcome was greater when comparing ICU patients versus non-ICU patients
      than when comparing tigecycline recipients versus nonrecipients. IMPLICATIONS:
      Propensity scoring should be examined carefully to optimize its effects.
      Moreover, propensity scoring only addresses bias and confounding in nonrandomized
      studies that are attributable to variables contained within the dataset (ie, so
      called "observables") and not to other variables that may influence the
      relationship between outcomes and other independent variables.

PMID- 27866661
TI  - A critical question for NEC researchers: Can we create a consensus definition of
      NEC that facilitates research progress?
AB  - In the last decades the reported incidence of preterm necrotizing enterocolitis
      (NEC) has been declining in large part due to implementing comprehensive NEC
      prevention initiatives, including breast milk feeding, standardized feeding
      protocols, transfusion guidelines, and antibiotic stewardship and improving the
      rigor with which non-NEC cases are excluded from NEC data. However, after more
      than 60 years of NEC research in animal models, the promise of a "magic bullet"
      to prevent NEC has yet to materialize. There are also serious issues involving
      clinical NEC research. There is a lack of a common, comprehensive definition of
      NEC. National datasets have their own unique definition and staging definitions.
      Even within academia, randomized trials and single center studies have widely
      disparate definitions. This makes NEC metadata of very limited value. The world
      of neonatology needs a comprehensive, universal, consensus definition of NEC. It
      also needs a de-identified, international data warehouse.

PMID- 27866660
TI  - Graft copolymerization of acrylamide on chitosan-co-chitin and its application
      for immobilization of Aspergillus sp. RL2Ct cutinase.
AB  - The synthesis of chitosan (Chs) and chitin (Chi) copolymer and grafting of
      acrylamide (AAm) onto the synthesized copolymer have been carried out by chemical
      methods. The grafted copolymer was characterized by FTIR, SEM and XRD. The
      extracellular cutinase of Aspergillus sp. RL2Ct (E.C. 3.1.1.3) was purified to
      4.46 fold with 16.1% yield using acetone precipitation and DEAE sepharose ion
      exchange chromatography. It was immobilized by adsorption on the grafted
      copolymer. The immobilized enzyme was found to be more stable then the free
      enzyme and has a good binding efficiency (78.8%) with the grafted copolymer. The
      kinetic parameters KM and Vmax for free and immobilized cutinase were found to be
      0.55mM and 1410MUmolmin-1mg-1 protein, 2.99mM and 996MUmolmin-1mg-1 protein,
      respectively. The immobilized cutinase was recycled 64 times without considerable
      loss of activity. The matrix (Chs-co-Chi-g-poly(AAm)) prepared and cutinase
      immobilized on the matrix have potential applications in enzyme immobilization
      and organic synthesis respectively.

PMID- 27866663
TI  - [Dermatoscopy of breast melanoma in women].

PMID- 27866662
TI  - Should we believe in transfusion-associated enterocolitis? Applying a GRADE to
      the literature.
AB  - Numerous observational studies appear to demonstrate an association between
      packed red blood cell (pRBC) transfusions and necrotizing enterocolitis (NEC).
      However, the limited numbers of randomized controlled trials (RCTs) do not
      support a causal relationship between pRBC transfusion and NEC. We sought to
      determine the quality of the evidence behind transfusion-associated necrotizing
      enterocolitis (TANEC), and to formulate a GRADE-based recommendation regarding
      transfusion practices to reduce the risk of TANEC. A systematic search including
      MEDLINE, Embase, CINAHL, the Cochrane Central Register of Controlled Trials and
      clinical trials registries was performed for studies assessing the association
      between transfusion and NEC. Teams of two paired reviewers independently screened
      studies for eligibility, assessed risk of bias using the GRADE framework, and
      collected data from each eligible study. We examined studies for two time points
      following transfusion: within 48h if this was available, and otherwise at any
      time after transfusion. In total, 23 observational studies and three RCTs met
      inclusion criteria. The average rating for the quality of evidence of individual
      studies was between "very low" and "low." On pooling studies for GRADE review, we
      observed an inconsistency of results. This led to a final overall quality of
      "very low" for the evidence for an association between transfusions and
      necrotizing enterocolitis. The pooled outcome of NEC for observational/case
      control studies was an odds ratio of 1.13 (95% CI: 0.99-1.29) when TANEC was
      defined as occurring within 48 hours of transfusion. For NEC occurring at any
      time post-transfusion, the pooled OR was 1.95 (1.60-2.38). Conversely, the pooled
      outcome of NEC for the RCT data had an odds ratio of 0.6 (0.3, 1.21) with NEC
      being less frequent in the liberal transfusion group compared to the restrictive
      transfusion group. The overall quality of the evidence for TANEC is "very low,"
      suggesting very little confidence in the effect estimate. RCT data tended toward
      apparent protection against NEC. The available evidence is not sufficient to
      support a practice recommendation around pRBC transfusions in the context of
      preventing the development of NEC.

PMID- 27866664
TI  - Introduction: Social Return On Investment (SROI).
AB  - An introduction to the issue Social Return On Investment (SROI), including an
      overview of problems prompting this special issue, plus definitions and examples
      of terms in this exciting, burgeoning area of cost-inclusive evaluation.

PMID- 27866665
TI  - "Giant cell reparative tumor: An exceptional differential diagnosis for a lytic
      lesion of the temporal bone".
AB  - BACKGROUND AND IMPORTANCE: Giant cell reparative granuloma is a very rare benign
      osteolytic lesion. It typically arises in the mandible and rarely involves the
      skull. CLINICAL PRESENTATION: A 25-year-old male was admitted in August 2002 for
      a painless left preauricular mass of several months duration. CT scan revealed an
      osteolytic extradural lesion located in the temporal bone, with extension to
      infratemporal fossa. We performed a surgical partial resection of the tumour via
      a frontotemporal approach. At 36 months after surgery, the lesion continued
      growth and subsequently we decided to perform a preauricular infratemporal
      approach. After a ten year-follow-up, the patient remained asymptomatic and a
      small tumour remnant was visible and stable. CONCLUSION: Giant cell reparative
      granulomas that originate from the temporal bone are exceptional. There are no
      typical radiological features of this disease. Diagnosis is confirmed by analysis
      of the surgical specimen. Tumor growth requires surgical resection.

PMID- 27866666
TI  - Why is there no "c" in nursing?

PMID- 27866667
TI  - CMS overhauls nursing facility regulations.

PMID- 27866668
TI  - Long term care nursing competence and related factors among Taiwanese nurses: A
      national survey for those who completed the LTC training course.
AB  - The aim of this study was to explore Taiwanese nurses' LTC competence and to
      examine its relationship with their LTC-related knowledge, care intention, and
      practical experience. The total sampling was selected from nurses who
      participated in a 2013 LTC course offered by the Ministry of Health and Welfare.
      Participants in this study (n = 122) voluntarily provided email addresses and
      responded to an online survey. A self-developed scale with acceptable reliability
      and validity was used for data collection. Findings from this study showed median
      high levels of LTC nursing competence, which was found to be positively
      correlated with LTC knowledge, care intention, practical experience, continuing
      education, and marital status. The study revealed that through on-the-job
      training, nurses' LTC knowledge, care intention, practical experience and nursing
      competence can be improved, which will benefit the quality of care for LTC
      clients.

PMID- 27866669
TI  - Conjoined twins after in-vitro fertilization.

PMID- 27866670
TI  - [Shift the skin paddle in an additional incision improves the result: Study of a
      series of 82 breast reconstructions by latissimus dorsi flap and prosthesis
      implantation at 10 years].
AB  - : The position of the skin paddle on the breast area is a fundamental element for
      the breast reconstructions by latissimus dorsi flap and prosthesis implantation.
      Should, as Millard advocated, to recreate the initial defect and include it in
      the mastectomy scar or is it better in an additional incision as have others
      authors. This study compares the long-term morphological results of these two
      attitudes, with or without additional incision. PATIENTS AND METHODS: Eighty-two
      breast reconstructions by latissimus dorsi flap and prosthesis implantation, with
      a mean follow-up of 9.5 years were scored from 1 to 5 by a panel of expert and
      non-expert. The patients scored also their own reconstruction. Various parameters
      of the reconstructed breast were thus evaluated. We compared the results,
      according to the positioning of the skin paddle: with additional incision (50
      cases); without additional incision (32 cases). The characteristics of the
      mastectomy scar on the breast area, high or low, horizontal or oblique, defined 6
      groups where the results of the 2 surgical options were compared. RESULTS: Only
      the reconstructions with additional incision get significantly higher results
      than those without additional incision (P<0.05). This involves the two panels, in
      the case of high mastectomy scars. In the others cases the additional incision is
      not essential. CONCLUSIONS: If the realization of an additional incision can be
      perceived like misfit on an area already "mutilated", we plead for this solution
      in selected cases. This provides a benefit stable in time, in terms of overall
      results, shape and even rendering scar.

PMID- 27866671
TI  - Biology enters the scene-a new perspective on bilingualism, cognition, and
      dementia.
AB  - The question of whether bilingualism can influence cognitive functions in healthy
      aging as well as in brain diseases is currently a topic of an intense debate. In
      a study published in this issue of the "Neurobiology of Ageing", Estanga et al.
      are breaking new ground by combining cognitive and biological approaches. Based
      on the data from the Guipuzkoa Alzheimer Project, they report that, compared with
      monolinguals, early bilinguals are not only characterized by a better cognitive
      performance in several domains and a lower prevalence of Alzheimer's disease but
      also by lower levels of t-tau in their cerebrospinal fluid. We suggest that
      sustained activation of noradrenergic signaling pathways associated with
      bilingualism could provide a possible mechanism linking results of this study
      with previous observations of delayed onset of dementia in bilinguals.

PMID- 27866672
TI  - Chemical and biochemical thermodynamics: Is it time for a reunification?
AB  - The thermodynamics of chemical reactions in which all species are explicitly
      considered with atoms and charge balanced is compared with the transformed
      thermodynamics generally used to treat biochemical reactions where atoms and
      charges are not balanced. The transformed thermodynamic quantities suggested by
      Alberty are obtained by execution of Legendre transformation of the usual
      thermodynamic potentials. The present analysis demonstrates that the transformed
      values for DeltarG'0 and DeltarH'0can be obtained directly without performing
      Legendre transformations by simply writing the chemical reactions with all the
      pseudoisomers explicitly included and charges balanced. The appropriate
      procedures for computing the stoichiometric coefficients for the pseudoisomers
      are fully explained by means of an example calculation for the biochemical ATP
      hydrolysis reaction. It is concluded that the analysis has reunited the "two
      separate worlds" of conventional thermodynamics and transformed thermodynamics.
      In addition, it is also shown that the value of the conditional Gibbs energy of
      reaction, DeltarG', for a biochemical reaction is the same of the value of
      DeltarG for any chemical reaction involving pseudoisomers of the biochemical
      reagents.

PMID- 27866673
TI  - Surveillance of tedizolid activity and resistance: In vitro susceptibility of
      Gram-positive pathogens collected over 5 years from the United States and Europe.
AB  - In vitro activity of tedizolid and comparators against 11,231 Gram-positive
      clinical isolates from the United States (84 centers) and Europe (115 centers)
      were summarized as part of the Surveillance of Tedizolid Activity and Resistance
      program between 2009 and 2013. Susceptibility testing was performed according to
      Clinical Laboratory and Standards Institute (CLSI) guidelines. Minimum inhibitory
      concentration (MIC) interpretations were based on CLSI and European Committee on
      Antimicrobial Susceptibility Testing criteria. Tedizolid inhibited 99.7% of all
      isolates at MIC <=0.5 mg/L; activity was similar regardless of methicillin or
      vancomycin resistance phenotypes of Staphylococcus aureus and enterococci,
      respectively. Tedizolid MIC >1 mg/L was reported for 3 S. aureus, 4 coagulase
      negative staphylococci, and 2 enterococcal isolates; all streptococci were
      inhibited at MIC <=0.5 mg/L. Tedizolid was >=4-fold more potent than linezolid
      against all groups, including resistant phenotypes. Tedizolid had potent/stable
      activity against a large, contemporary collection of Gram-positive clinical
      isolates, with low rates of resistance.

PMID- 27866674
TI  - Quantitative T2 mapping for detection and quantification of thrombophlebitis in a
      rabbit model.
AB  - Short peripheral catheter thrombophlebitis (SPCT), a sterile inflammation of the
      vein wall, is the most common complication associated with short peripheral
      catheters (SPCs) and affects up to 80% of hospitalized patients receiving IV
      therapy. Extensive research efforts have been devoted for improvement and
      optimization of the catheter material, but means for examination of any novel
      design are limited, inaccurate and require costly comprehensive pre-clinical and
      clinical trials. Therefore, there is a conclusive need for a reliable
      quantitative method for evaluation of SPCT, in particular for research purposes
      examining the thrombophlebitis-related symptoms of any novel catheter design. In
      this study, we developed for the first time a quantitative MRI based tool for
      evaluation of SPCT. The extent and severity of SPCT caused by two different
      commercially available SPCs with known predisposition for thrombophlebitis, were
      studied in a rabbit model. MRI analysis was consistent with the standardized
      pathology evaluation and showed remarkable difference in the percent of edema
      between the experimental groups. These differences were in line with previous
      studies and provide evidence that this type of analysis may be useful for future
      assessment of SPCT in vivo. As a non-invasive method, it may constitute a cost
      effective solution for examination of new catheters and other medical devices,
      thereby reducing the need for animal sacrifice.

PMID- 27866675
TI  - Hemodynamics of patient-specific aorta-pulmonary shunt configurations.
AB  - Optimal hemodynamics in aorta-pulmonary shunt reconstruction is essential for
      improved post-operative recovery of the newborn congenital heart disease patient.
      However, prior to in vivo execution, the prediction of post-operative
      hemodynamics is extremely challenging due to the interplay of multiple
      confounding physiological factors. It is hypothesized that the post-operative
      performance of the surgical shunt can be predicted through computational blood
      flow simulations that consider patient size, shunt configuration, cardiac output
      and the complex three-dimensional disease anatomy. Utilizing only the routine
      patient-specific pre-surgery clinical data sets, we demonstrated an intelligent
      decision-making process for a real patient having pulmonary artery atresia and
      ventricular septal defect. For this patient, a total of 12 customized candidate
      shunt configurations are contemplated and reconstructed virtually using a sketch
      based computer-aided anatomical editing tool. Candidate shunt configurations are
      evaluated based on the parameters that are computed from the flow simulations,
      which include 3D flow complexity, outlet flow splits, shunt patency, coronary
      perfusion and energy loss. Our results showed that the modified Blalock-Taussig
      (mBT) shunt has 12% higher right pulmonary artery (RPA) and 40% lower left
      pulmonary artery (LPA) flow compared to the central shunt configuration. Also,
      the RPA flow regime is distinct from the LPA, creating an uneven flow split at
      the pulmonary arteries. For all three shunt sizes, right mBT innominate and
      central configurations cause higher pulmonary artery (PA) flow and lower coronary
      artery pressure than right and left mBT subclavian configurations. While there is
      a trade-off between energy loss, flow split and coronary artery pressure,
      overall, the mBT shunts provide sufficient PA perfusion with higher coronary
      artery pressures and could be preferred for similar patients having PA overflow
      risk. Central shunts would be preferred otherwise particularly for cases with
      very low PA overflow risk.

PMID- 27866676
TI  - Human soleus sarcomere lengths measured using in vivo microendoscopy at two ankle
      flexion angles.
AB  - The forces generated by the soleus muscle play an important role in standing and
      locomotion. The lengths of the sarcomeres of the soleus affect its force
      generating capacity, yet it is unknown how sarcomere lengths in the soleus change
      as a function of ankle flexion angle. In this study, we used microendoscopy to
      measure resting sarcomere lengths at 10 degrees  plantarflexion and 20 degrees 
      dorsiflexion in 7 healthy individuals. Mean sarcomere lengths at 10 degrees 
      plantarflexion were 2.84+/-0.09um (mean+/-S.E.M.), near the optimal length for
      sarcomere force generation. Sarcomere lengths were 3.43+/-0.09um at 20 degrees 
      dorsiflexion, indicating that they were longer than optimal length when the ankle
      was in dorsiflexion and the muscle was inactive. Our results indicate a smaller
      sarcomere length difference between two ankle flexion angles compared to
      estimates from musculoskeletal models and suggest why these models frequently
      underestimate the force-generating capacity of the soleus.

PMID- 27866677
TI  - Pressure drop and arterial compliance - Two arterial parameters in one
      measurement.
AB  - Coronary artery pressure-drop and distensibility (compliance) are two major,
      seemingly unrelated, parameters in the cardiovascular clinical setting, which are
      indicative of coronary arteries patency and atherosclerosis severity. While
      pressure drop is related to flow, and therefore serves as a functional indicator
      of a stenosis severity, the arterial distensibility is indicative of the arterial
      stiffness, and hence the arterial wall composition. In the present study, we
      hypothesized that local pressure drops are dependent on the arterial
      distensibility, and hence can provide information on both indices. The clinical
      significance is that a single measurement of pressure drop could potentially
      provide both functional and bio-mechanical metrics of lesions, and thus assist in
      real-time decision making prior to stenting. The goal of the current study was to
      set the basis for understanding this relationship, and define the accuracy and
      sensitivity required from the pressure measurement system. The investigation was
      performed using numerical fluid-structure interaction (FSI) simulations,
      validated experimentally using our high accuracy differential pressure
      measurement system. Simplified silicone mock coronary arteries with zero to
      intermediate size stenoses were used, and various combinations of arterial
      distensibility, diameter, and flow rate were simulated. Results of hyperemic flow
      cases were also compared to fractional flow reserve (FFR). The results indicate
      the potential clinical superiority of a high accuracy pressure drop-based
      parameter over FFR, by: (i) being more lesion-specific, (ii) the possibility to
      circumvent the FFR dependency on pharmacologically-induced hyperemia, and, (iii)
      by providing both functional and biomechanical lesion-specific information.

PMID- 27866678
TI  - Patient-specific CFD models for intraventricular flow analysis from 3D ultrasound
      imaging: Comparison of three clinical cases.
AB  - BACKGROUND: As the intracardiac flow field is affected by changes in shape and
      motility of the heart, intraventricular flow features can provide diagnostic
      indications. Ventricular flow patterns differ depending on the cardiac condition
      and the exploration of different clinical cases can provide insights into how
      flow fields alter in different pathologies. METHODS: In this study, we applied a
      patient-specific computational fluid dynamics model of the left ventricle and
      mitral valve, with prescribed moving boundaries based on transesophageal
      ultrasound images for three cardiac pathologies, to verify the abnormal flow
      patterns in impaired hearts. One case (P1) had normal ejection fraction but low
      stroke volume and cardiac output, P2 showed low stroke volume and reduced
      ejection fraction, P3 had a dilated ventricle and reduced ejection fraction.
      RESULTS: The shape of the ventricle and mitral valve, together with the pathology
      influence the flow field in the left ventricle, leading to distinct flow
      features. Of particular interest is the pattern of the vortex formation and
      evolution, influenced by the valvular orifice and the ventricular shape. The base
      to-apex pressure difference of maximum 2mmHg is consistent with reported data.
      CONCLUSION: We used a CFD model with prescribed boundary motion to describe the
      intraventricular flow field in three patients with impaired diastolic function.
      The calculated intraventricular flow dynamics are consistent with the diagnostic
      patient records and highlight the differences between the different cases. The
      integration of clinical images and computational techniques, therefore, allows
      for a deeper investigation intraventricular hemodynamics in patho-physiology.

PMID- 27866679
TI  - [Hodgkin and non-Hodgkin lymphoma of adolescents and young adults].
AB  - Lymphoma is one of the most frequent cancers in adolescent and young adults.
      Hodgkin Lymphoma is curable in more than 90% of cases. Recent pediatric and
      adults protocols aimed to decrease long term toxicities (mostly gonadic and
      cardiovascular) and secondary malignancies, reducing the use of alkylating agents
      and limiting radiation fields. Risk-adapted strategies, using positron emission
      tomography staging, are about to become a standard, both in adult and pediatric
      protocols. These approaches allow obtaining excellent results in adolescents with
      Hodgkin lymphoma. On the other hand, treatment of adolescents with diffuse large
      B-cell lymphoma raises some questions. Even through children have good outcomes
      when treated with risk-adapted strategies, adolescents who are between 15 and 18
      years old seem to experience poorer survivals, whereas patients older than 18
      years old have globally the same outcome than older adults. This category of
      patient needs a particular care, based on a tight coordination between adults and
      pediatric oncologists. Primary mediastinal lymphomas, a subtype of BLDCL frequent
      in young adult population, exhibits poorer outcomes in children or young
      adolescent population than in older ones. Taking together, B-cell lymphoma
      benefited from recent advances in immunotherapy (in particular with the extended
      utilization of rituximab) and metabolic response-adapted strategies. In
      conclusion, adolescent and young adult's lymphomas are very curable diseases but
      require a personalized management in onco-hematological units.

PMID- 27866680
TI  - ARLTS1, potential candidate gene in familial aggregation of hematological
      malignancies.
AB  - INTRODUCTION: Genetic predisposition to familial hematological malignancies was
      previously described through several epidemiological analyses, but the genetic
      basis remains unclear. The tumor-suppressor ARLTS1 gene was previously described
      in sporadic hematological malignancies and familial cancer context. METHODS: In
      this study, we sequence the ARLTS1 gene in 100 patients belonging to 88
      independent Tunisian and French families. RESULTS: After gene sequencing, we
      report 8 genetic variations, most of which were previously reported in several
      cancer forms. The most common variants were W149X and C148R and were previously
      associated to B-cell chronic lymphocytic leukemia and to high-risk of familial
      breast cancer. CONCLUSIONS: These results emphasize the fact that ARLTS1 gene
      mutations can be considered as a potential predisposing factor in familial
      hematological malignancies and other several cancer forms.

PMID- 27866681
TI  - [Psychosocial and developmental outcomes of TYAs with cancer: Are there any
      specific characteristics for the young adults?]
AB  - During the last few years, specific support devices and even dedicated units for
      teenagers and young adults (TYAs - patients grouped in the 15-25 years age group)
      appeared in oncology. If the existing literature review allows identifying many
      written work related to the experience of cancer during adolescence, resources
      about "young adults" are not only far less abundant, but rarely give the
      definition of what is a "young adult". Based on this observation, it appears
      necessary, at this stage of our practice, to question the definition and
      psychosocial outcomes of those psychiatrists and psychologists also call "young
      adults". Are they so different compared to teenagers? Do they have their own
      specificities? Based on the analysis of the general literature, we will seek to
      define the highlights of this moment of life and to identify their specific
      psychosocial and developmental outcomes. Thus, we will be able to study more
      accurately the experience of young adults facing cancer and the associated
      psychological side effects. Based on this analysis, we will present the issues
      which seemed to be specific in the psychological support of young adults and
      their relatives.

PMID- 27866683
TI  - Interventional laser surgery for oral potentially malignant disorders: a
      longitudinal patient cohort study.
AB  - Oral squamous cell carcinoma (OSCC) is a lethal disease, with rising incidence.
      There were 6767 new OSCC cases and 2056 deaths in the UK in 2011. Cancers are
      preceded by oral potentially malignant disorders (PMDs), recognizable mucosal
      diseases harbouring increased SCC risk, offering clinicians a 'therapeutic
      window' to intervene. Contemporary practice remains unable to predict lesion
      behaviour or quantify malignant transformation risk. No clear management
      guidelines exist and it is unclear from the literature whether early diagnosis
      and intervention prevents cancer. Between 1996 and 2014, 773 laser treatments
      were performed on 590 PMD patients in Newcastle maxillofacial surgery
      departments. The efficacy of the intervention was examined by review of the
      clinicopathological details and clinical outcomes of the patients (mean follow-up
      7.3 years). Histopathology required up-grading in 36.1% on examining excision
      specimens. Seventy-five percent of patients were disease-free, mostly younger
      patients with low-grade dysplasia; 9% exhibited persistent disease and were
      generally older with proliferative verrucous leukoplakia. Disease-free status was
      less likely for erythroleukoplakia (P=0.022), 'high-grade' dysplasia (P<0.0001),
      and with lichenoid inflammation (P=0.028). Unexpected OSCC was identified in
      12.0%, whilst 4.8% transformed to malignancy. Interventional laser surgery
      facilitates definitive diagnosis and treatment, allows early diagnosis of OSCC,
      identifies progressive disease, and defines outcome categories. Evidence is
      lacking that intervention halts carcinogenesis. Multicentre, prospective,
      randomized controlled trials are needed to confirm the efficacy of surgery.

PMID- 27866682
TI  - [Adolescent and Young Adults (AYAS) brain tumor national Web conference. On
      behalf of ANOCEF, GO-AJA and SFCE societies].
AB  - : The skills of adult versus pediatric neuro-oncologists are not completely
      similar though additive. Because the tumors and their protocols are different and
      the tolerance and expected sequelae are specific. Multidisciplinary meetings
      including adult and pediatric neuro-oncologists are warranted to share expertise.
      Since 2008, a weekly national web based conference was held in France. Any
      patient with the following criteria could be discussed: Adolescent and Young
      Adults aged between 15 and 25 years, and any adult with a pediatric type
      pathology, including medulloblastoma, germ cell tumors, embryonic tumors,
      ependymoma, pilocytic astrocytoma. RESULTS: Attendance during the year 2015 was
      as follows: 42 meetings were held; the median number of cases discussed at each
      meeting was 4 (1 to 8); the mean number of attendants was 7 (2 to 12). One
      hundred and sixty-eight cases concerning 121 patients were discussed. Mean age
      was 30 years old (7 to 67). Forty-eight percent were discussed at diagnosis. The
      patients had mostly medulloblastomas (40%), germ cell tumors (11%), ependymomas
      (11%), pineal tumors (7%) and embryonal tumors (8%). The rate of inclusion in
      protocols was increased since the opening of this web conference, especially for
      the germ cell tumor SIOP protocol that is opened without age restriction, and in
      RSMA standard risk or MEVITEM relapse adult medulloblastoma protocols.
      CONCLUSION: Multidisciplinary Web conference for AYAs is feasible and increases
      the inclusion rate in protocols. It should be developed further.

PMID- 27866685
TI  - Garrett Hardin's Tragic Sense of Life.
AB  - I discuss biologist Garrett Hardin's view of human nature, with examples from the
      background to his seminal 1968 essay "The Tragedy of the Commons" and his
      testimony before the US House of Representatives in the 1970s. Hardin saw the
      human species as being governed by deterministic laws of the same kind that
      controlled all other forms of life. Humans, as much as cattle and microbes, were
      in inevitable competition for space and resources. Equal parts Malthusian
      political economy and Cold War systems science, his view was the survival of the
      human race depended on obeying these iron laws. Human freedom was the recognition
      of-and obedience to-its nature. This determination for humanity to act within the
      strictures placed on itself by its own nature was what he called "lifeboat
      ethics." In order for the citizens of the rich countries to survive, many in the
      Third World would have to die. In this sense I characterize Hardin's sense of
      life as tragic, both as a play on the title of his famous essay, and to emphasize
      his view that the problem of human population growth had no 'win-win' solutions.

PMID- 27866684
TI  - Was Queen Jane Seymour (1509-1537) Delivered by a Cesarean Section?
AB  - No direct evidence documents exactly how Jane Seymour gave birth on October 12,
      1537. Several later commentators have raised cesarean birth as an option. This
      paper tries to establish the probable cause of Jane Seymour's death in accordance
      with present-day knowledge of obstetrics and whether or not a cesarean section
      could have been actually performed in sixteenth-century England. It appears
      almost certainly that there were no obstetrical indications that would have led
      the Queen's physicians to operate on her, a surgeon was not present at her
      delivery, cesarean section on a living woman was not regularly performed in
      England in 1537, puerperium events do not support surgery, and the existing pro
      cesarean confirmation was politically motivated. Therefore, the most likely mode
      of Jane Seymour's delivery was vaginal rather than cesarean.

PMID- 27866686
TI  - Size, Loading Efficiency, and Cytotoxicity of Albumin-Loaded Chitosan
      Nanoparticles: An Artificial Neural Networks Study.
AB  - When designing nanoparticles for drug delivery, many variables such as size,
      loading efficiency, and cytotoxicity should be considered. Usually, smaller
      particles are preferred in drug delivery because of longer blood circulation time
      and their ability to escape from immune system, whereas smaller nanoparticles
      often show increased toxicity. Determination of parameters which affect size of
      particles and factors such as loading efficiency and cytotoxicity could be very
      helpful in designing drug delivery systems. In this work, albumin (as a protein
      drug model)-loaded chitosan nanoparticles were prepared by polyelectrolyte
      complexation method. Simultaneously, effects of 4 independent variables including
      chitosan and albumin concentrations, pH, and reaction time were determined on 3
      dependent variables (i.e., size, loading efficiency, and cytotoxicity) by
      artificial neural networks. Results showed that concentrations of initial
      materials are the most important factors which may affect the dependent
      variables. A drop in the concentrations decreases the size directly, but they
      simultaneously decrease loading efficiency and increase cytotoxicity. Therefore,
      an optimization of the independent variables is required to obtain the most
      useful preparation.

PMID- 27866687
TI  - Glibenclamide Nanocrystals in a Biodegradable Chitosan Patch for Transdermal
      Delivery: Engineering, Formulation, and Evaluation.
AB  - Glibenclamide (GBD) nanocrystals (D50 = 429 nm) were engineered by applying
      combined precipitation and homogenization procedures. GBD crystallinity was
      maintained during the nanonization process as revealed by differential scanning
      calorimetry and X-ray analyses. Nanonized and micronized GBD were incorporated
      into chitosan solutions to fabricate transdermal delivery systems (TDDSs), nano-
      and micro-GBD, respectively. The fabricated TDDSs displayed satisfactory
      physicochemical characteristics without substantial aggregation of GBD
      nanocrystals during the casting and drying procedures. Within 24 hours, about 85
      +/- 3.1% of the GBD content was released from nano-GBD, compared to 61 +/- 3.9%
      from micro-GBD. Cumulative permeation of GBD from nano-GBD after 24 hours was 498
      +/- 33.35 compared to 362 +/- 25.25 MUg/cm2 from micro-GBD. The calculated flux
      across rat skin for nano-GBD was 23.14 compared to 13.64 MUg/cm2/h for micro-GBD,
      with an enhancement factor of 1.7. In vivo assessment clearly revealed the
      enhanced efficacy of nano-GBD to reduce blood glucose levels and counteract the
      induced hyperglycemia in tested animals compared to micro-GBD (p < 0.5).
      Simultaneously, the nano-GBD was able to maintain higher drug concentration for
      longer time (24 hours, p < 0.5) and minimize intense action and hypoglycemia
      associated with GBD oral therapy (p < 0.5).

PMID- 27866688
TI  - Optimal mixing rate in linear solvent strength gradient liquid chromatography.
      Balanced mixing program.
AB  - The mixing rate (Rphi) is the temporal rate of increase in the solvent strength
      in gradient LC. The optimal Rphi (Rphi,Opt) is the one at which a required peak
      capacity of gradient LC analysis is obtained in the shortest time. The balanced
      mixing program is a one where, for better separation of early eluting solutes,
      the mixing ramp is preceded by a balanced isocratic hold of the duration
      depending on Rphi. The improvement in the separation of the earlier eluites due
      to the balanced programming has been evaluated. The value of Rphi,Opt depends on
      the solvent composition range covered by the mixing ramp and on the column
      pressure conditions. The Rphi,Opt for a column operating at maximum instrumental
      pressure is different from Rphi,Opt for a column operating below the instrumental
      pressure limit. On the other hand, it has been shown that the difference in the
      Rphi,Opt values under different conditions is not very large so that a single
      default Rphi previously recommended for gradient analyses without the isocratic
      hold also yields a good approximation to the shortest analysis time for all
      conditions in the balanced analyses. With or without the initial balance
      isocratic hold, the recommended default Rphi is about 5%/t0 (5% increase in the
      solvent strength per each t0-long increment in time) for small-molecule samples,
      and about an order of magnitude slower (0.5%/t0) for protein samples. A
      discussion illustrating the use of the optimization criteria employed here for
      the techniques other than LSS gradient LC is included.

PMID- 27866689
TI  - Characterization of non-specific protein adsorption induced by triazole groups on
      the chromatography media using Cu (I)-catalyzed alkyne-azide cycloaddition
      reaction for ligand immobilization.
AB  - As an efficient and facile reaction, click chemistry has been growingly used in
      the preparation of chromatography media for immobilizing varying types of
      ligands. For the widely used Cu (I)-catalyzed alkyne-azide click reaction, a 1,
      2, 3-triazole group will be inevitably introduced in the molecular linkage, which
      could give rise to unexpected non-specific adsorption especially for the media
      employing small compound ligands or high ligand density. Triazole-induced non
      specific protein adsorption on sepharose resins was evaluated systematically in
      this work, by considering the effects of triazole content, length of spacer arm,
      and solution conditions. We found that triazole content of a resin played the key
      role. Protein adsorption became significant when the media was coupled with
      triazole at a medium density (about 60MUmol/mL gel), and the binding amount
      further increased with triazole density. The resin with triazole content of about
      100MUmol/mL gel could adsorb human IgG, bovine serum albumin and lysozyme at the
      amount of 13.6, 30.0, and 5.1mg/mL respectively. Proteins tended to be adsorbed
      at higher amount as the pH of solution approached their isoelectric points, and
      increasing salt concentration could reduce triazole-induced adsorption but only
      within limited extent. This study can facilitate reasonable application of click
      chemistry in the synthesis of chromatography media, by providing some basic
      principles for optimizing structural properties of separation media and choosing
      suitable solution conditions.

PMID- 27866690
TI  - Method to determine the true modulation ratio for comprehensive two-dimensional
      gas chromatography.
AB  - A new method is presented to determine the true modulation ratio, MR, from the
      measurable effective modulation ratio, MR*, in comprehensive two-dimensional gas
      chromatography, GC*GC, without the requirement for a detector at the end of the
      primary column. The method was developed through the investigation of modulator
      induced band broadening, as a function of 1Wb and the selected modulation period,
      PM, for simulated GC*GC data, by first defining primary column 1D peak(s) and
      simulating the modulation process. Gaussian curve fitting is used to model each
      modulated secondary column separation peaklet, 2D, in the unfolded GC*GC data to
      accurately determine the maxima of the peaklet distribution, followed by Gaussian
      curve fitting to the maxima to determine the effective 1D peak profile and width,
      1Wb*. The relationship between 1Wb and 1Wb* is studied as a function of the
      effective modulation ratio, MR*, which is 1Wb* divided by PM, in order to
      determine the true modulation ratio, MR, which is 1Wb divided by PM. We explore
      how peak sampling phase (in-phase and out-of-phase) plays a role in the
      relationship between MR and MR*. Experimental validation of the simulated results
      is also provided, to span a range of commonly implemented conditions with typical
      1Wb (2-4.5s) and PM (0.25-8s). Use of MR<2 significantly broadens the 1D peak
      (MR*>=1.2MR) corresponding to a loss in 1D peak capacity, 1nc>=20%. The new
      method relies upon mapping from MR* to MR, which is discussed in relation to peak
      capacity theories for GC*GC. It is found that optimizing 1nc in GC*GC requires
      that 1Wb is minimized and must be sampled with a sufficiently short PM (1-2s) to
      minimize modulator induced band broadening and a subsequent reduction in the
      effective 1D peak capacity.

PMID- 27866693
TI  - An unexpected complication of acute pancreatitis: Intra-cardiac thrombus.
AB  - Left atrial thrombus after acute pancreatitis (AP) is a rare clinical statement.
      Because of induction of systemic prothrombotic process by AP; some patients with
      underlying risk factors may develop an intra-cardiac thrombus. We present a
      53years-old-woman with moderate mitral stenosis and atrial fibrillation. However
      the patient was under warfarin treatment, she developed a big left atrial big
      thrombus which was originated from left atrial appendage after she was suffered
      from AP.

PMID- 27866691
TI  - Vocal Parameters and Self-Perception in Individuals With Adductor Spasmodic
      Dysphonia.
AB  - OBJECTIVE: The study aimed to compare and correlate perceptual-auditory analysis
      of vocal parameters and self-perception in individuals with adductor spasmodic
      dysphonia before and after the application of botulinum toxin. STUDY DESIGN: This
      is a prospective cohort study. METHODS: Sixteen individuals with a diagnosis of
      adductor spasmodic dysphonia were submitted to the application of botulinum toxin
      in the thyroarytenoid muscle, to the recording of a voice signal, and to the
      Voice Handicap Index (VHI) questionnaire before the application and at two time
      points after application. Two judges performed a perceptual-auditory analysis of
      eight vocal parameters with the aid of the Praat software for the visualization
      of narrow band spectrography, pitch, and intensity contour. RESULTS: Comparison
      of the vocal parameters before toxin application and on the first return revealed
      a reduction of oscillation intensity (P = 0.002), voice breaks (P = 0.002), and
      vocal tremor (P = 0.002). The same parameters increased on the second return. The
      degree of severity, strained-strangled voice, roughness, breathiness, and
      asthenia was unchanged. The total score and the emotional domain score of the VHI
      were reduced on the first return. There was a moderate correlation between the
      degree of voice severity and the total VHI score before application and on the
      second return, and a weak correlation on the first return. CONCLUSIONS:
      Perceptual-auditory analysis and self-perception proved to be efficient in the
      recognition of vocal changes and of the vocal impact on individuals with adductor
      spasmodic dysphonia under treatment with botulinum toxin, permitting the
      quantitation of changes along time.

PMID- 27866692
TI  - Does the number of emergency medical technicians affect the neurological outcome
      of patients with out-of-hospital cardiac arrest?
AB  - BACKGROUND: It is unclear whether the number of paramedics in an ambulance
      improves the outcome of patients with out-of-hospital cardiac arrest (OHCA) or
      not. METHODS AND RESULTS: This study was a prospective, observational study
      conducted on patients with OHCA. Patients were divided into the One-paramedic
      group (Group O) and the Two-or-more-paramedic group (Group T) and we analyzed the
      differences. Patients who were treated with only basic life support during
      transportation, and whose cause of cardiac arrest were extrinsic cause such as
      trauma and poisoning were excluded. Good neurological outcome was defined as
      cerebral performance category (CPC) 1 or 2. In Group O, there were 1516 patients
      (male/female, 922/594). In Group T, there were 2932 patients (male/female,
      1798/1134). Return of spontaneous circulation (ROSC) was obtained in 528 patients
      (34.8%) in Group O and 1058 patients (36.1%) in Group T (p=0.589). 320 patients
      (21.1%) in Group O and 656 patients (22.4%) in Group T were admitted to hospital
      after ROSC (p=0.461). At 90days, there were 57 survivors (3.8%) in Group O and
      114 survivors (3.9%) in Group T (p=0.873). At 90days, 14 patients (0.9%) in Group
      T had a CPC of 1 or 2, while 30 patients (1.0%) in Group T did so (p=0.87). From
      the results of logistic regression analysis, age [odds ratio (OR): 0.983, 95%
      confidence interval (CI): 0.952-0.993], witnessed OHCA (OR: 4.583, 95% CI: 1.587
      13.234), and shockable rhythm as first documented (OR: 19.67, 95% CI: 9.181
      42.13) were associated with good outcome. CONCLUSION: The number of paramedics in
      an ambulance did not affect the outcome in OHCA patients.

PMID- 27866694
TI  - Spontaneously resolved STEMI after a hymenoptera sting.

PMID- 27866695
TI  - Does formulation matter? A systematic review and meta-analysis of oral versus
      long-acting antipsychotic studies.
AB  - Recently, many authors highlighted the potential advantages of a broader
      prescription of long-acting injectable antipsychotics (LAIs) based on various
      assumptions, including favorable pharmacokinetic features. In this systematic
      review, data from randomized controlled trials comparing LAIs versus the oral
      formulation of the same antipsychotic were meta-analyzed in order to ascertain
      whether the route of administration may be associated with a different efficacy
      and tolerability profile. Of 21 included studies, 18 contributed to the meta
      analysis, providing data for risperidone, olanzapine, aripiprazole,
      zuclopenthixol, fluphenazine and haloperidol. For all drugs, the number of
      dropouts for any reason (primary outcome) did not differ between the two
      formulations, except for a small effect in favor of LAI aripiprazole (2
      comparisons; 986 patients; relative risk (RR) 0.78; 95% confidence interval (CI)
      0.64 to 0.95). Similarly, no differences emerged in terms of dropouts for adverse
      events, extrapyramidal symptoms, prolactin increase (except for a small advantage
      for LAI risperidone), weight gain, non-response rate, relapse rate, and dropouts
      for inefficacy (except for a small advantage for oral olanzapine). Data on
      aripiprazole proved to be of high quality according to the GRADE approach
      (Grading of Recommendations, Assessment, Development and Evaluation), therefore
      we are confident that the effect estimate is close to the true effect. Data on
      risperidone were of moderate quality, while data on olanzapine, fluphenazine,
      zuclopenthixol and haloperidol were of low quality. In conclusion, there is no
      robust evidence to support doctors in choosing LAI instead of oral formulations
      in order to obtain better tolerability and efficacy.

PMID- 27866697
TI  - Development and capture of soft tissue contours at time of implant placement.
AB  - A technique is described which will generate a customized healing abutment for a
      dental implant to allow the development of ideal soft tissue contours. With
      implant position and soft tissue contours defined at surgery, customized
      impression techniques can be used to capture those details and help generate the
      definitive implant-supported restoration. This workflow reduces the number of
      patient visits.

PMID- 27866696
TI  - Equivalent Young's modulus of composite resin for simulation of stress during
      dental restoration.
AB  - OBJECTIVES: For shrinkage stress simulation in dental restoration, the elastic
      properties of composite resins should be acquired beforehand. This study proposes
      a formula to measure the equivalent Young's modulus of a composite resin through
      a calculation scheme of the shrinkage stress in dental restoration. METHODS: Two
      types of composite resins remarkably different in the polymerization shrinkage
      strain were used for experimental verification: the methacrylate-type (Clearfil
      AP-X) and the silorane-type (Filtek P90). The linear shrinkage strains of the
      composite resins were gained through the bonded disk method. A formula to
      calculate the equivalent Young's moduli of composite resin was derived on the
      basis of the restored ring substrate. Equivalent Young's moduli were measured for
      the two types of composite resins through the formula. Those values were applied
      as input to a finite element analysis (FEA) for validation of the calculated
      shrinkage stress. SIGNIFICANCE: Both of the measured moduli through the formula
      were appropriate for stress simulation of dental restoration in that the
      shrinkage stresses calculated by the FEA were in good agreement within 3.5% with
      the experimental values. The concept of equivalent Young's modulus so measured
      could be applied for stress simulation of 2D and 3D dental restoration.

PMID- 27866698
TI  - Comparison of margin discrepancy of complete gold crowns fabricated using
      printed, milled, and conventional hand-waxed patterns.
AB  - STATEMENT OF PROBLEM: The recent application of printing for the fabrication of
      dental restorations has not been compared and evaluated for margin discrepancy
      (margin fit) with restorations fabricated using milling and conventional hand
      waxing techniques. PURPOSE: The purpose of this in vitro study was to evaluate
      and compare margin discrepancy of complete gold crowns (CGCs) fabricated from
      printed, milled, and conventional hand-waxed patterns. MATERIAL AND METHODS:
      Thirty crown patterns were produced by each of 3 different methods: printed by
      ProJet DP 3000, milled by LAVA CNC 500, and hand waxed, then invested and cast
      into CGCs. Each crown was evaluated at 10 positions around the margin on the
      corresponding epoxy die under *50 light microscopy to determine the mean and
      maximum margin discrepancy. Measurements were made using a micrometer positioning
      stage. The results were compared by ANOVA (alpha=.05). RESULTS: Milled and hand
      waxed patterns were not statistically different from each other (P>.05), while
      printed patterns produced significantly higher mean and maximum margin
      discrepancy than milled and hand-waxed patterns (P<.05). CONCLUSIONS: Relative to
      margin discrepancy, the LAVA CNC 500 milled and hand-waxed patterns were not
      significantly different from each other. The ProJet DP 3000 printed patterns were
      significantly different from LAVA CNC 500 milled and hand-waxed patterns, with an
      overall poorer result. Fabricating CGCs from printed patterns produced a
      significantly higher number of crowns with unacceptable margin discrepancy (>120
      MUm).

PMID- 27866699
TI  - Recording the trajectory of mouth opening and closing for the fabrication of an
      occlusal splint.
AB  - Various attempts have been made to transfer the transverse hinge axis and
      mandibular movement pattern to the mechanical articulator and to fabricate dental
      prostheses with the fewest errors. However, the occlusal adjustment of a dental
      prosthesis is always necessary to ensure a precise intraoral fit even when the
      facebow transfer technique is used in the cast mounting procedure. This is
      because the true hinge axis is not obtained when the facebow is applied to a
      patient who exhibits a variable mandible movement pattern rather than a single
      rotational axis. This technique merges facial scanning data and digital data
      obtained from a diagnostic cast based on measurements of several landmarks of the
      anterior teeth and makes it possible to design a dental prosthesis while
      considering the mandibular opening and closing movements of the patient. This
      technique could be used to design prosthetic restorations, occlusal splints, and
      intermediate splints for orthognathic surgery and for complete mouth
      rehabilitation when changes in vertical dimensions are needed.

PMID- 27866700
TI  - Angiopoietin-related growth factor is independently associated with lower
      extremity peripheral arterial disease.
AB  - AIMS: The present study investigated the association of serum levels of
      angiopoietin-related growth factor (AGF) with lower extremity peripheral arterial
      disease (LEPAD). METHODS: The study group is comprised of 105 patients with lower
      extremity peripheral arterial disease. The control group consisted of 80
      individuals without lower extremity peripheral arterial disease. Serum AGF
      concentrations were determined by enzyme-linked immunosorbent assay. The
      relationship between AGF and clinical and biochemical parameters was studied.
      Besides, this study analyzed AGF levels in LEPAD patients according to disease
      severity and evaluated the prognostic value of AGF for amputation and mortality
      in LEPAD patients after a follow-up period of 1.7years. RESULTS: Median serum AGF
      levels were significantly higher in LEPAD group (103.70+/-64.69ng/mL) as compared
      with control group (53.83+/-37.87ng/mL) (P<0.001). In addition, T2DM patients
      with LEPAD exhibited markedly higher serum AGF concentrations (118.7+/
      60.90ng/mL) than those without LEPAD (60.23+/-32.62ng/mL) (P<0.0001). Moreover,
      LEPAD positively predicted AGF concentrations in multivariate linear regression
      analysis (P<0.0001). Serum AGF levels were independently associated with LEPAD in
      binary logistic regression analysis model. Among LEPAD patients, those with
      critical limb ischemia (n=43) showed higher AGF levels (124.9+/-73.9 vs. 88.98+/
      53.26ng/mL, P=0.01) compared with those with intermittent claudication (n=62).
      Furthermore, patients with the highest AGF tertile had an increased all-cause
      mortality and cardiovascular mortality (P=0.033 and P=0.025, respectively).
      CONCLUSIONS: Our results suggested that lower extremity peripheral artery disease
      was positively associated with AGF serum levels. High serum AGF level was a
      potential risk factor for LEPAD and associates with disease severity and poor
      outcome in LEPAD patients.

PMID- 27866701
TI  - Place of sodium-glucose cotransporter-2 inhibitors in East Asian subjects with
      type 2 diabetes mellitus: Insights into the management of Asian phenotype.
AB  - The burden of type 2 diabetes (T2DM) in East Asia is alarming. Rapid
      modernization and urbanization have led to major lifestyle changes and a
      tremendous increase in the prevalence of obesity, metabolic syndrome, and
      diabetes mellitus. The development of T2DM at a younger age, with lower body mass
      index, higher visceral adiposity, and more significant pancreatic beta-cell
      dysfunction compared to Caucasians are factors responsible for the increased
      prevalence of T2DM in East Asians. Sodium-glucose Cotransporter-2 (SGLT2)
      inhibitors (canagliflozin, dapaglifozin, empagliflozin, etc.) reduce renal
      glucose reabsorption, leading to favorable effects on glycemic, blood pressure,
      and weight control. The insulin-independent mechanism enables their use as
      monotherapy or combination therapy with insulin and other oral antidiabetic
      agents. The role of SGLT2 inhibitors in the management of T2DM among East Asians
      is an interesting area of research, given that East Asians have been proven to be
      uniquely different from Caucasians. This review provides comprehensive coverage
      of the available literature not only on the efficacy and safety, but also on the
      recent cardiovascular and renal outcomes of SGLT2 inhibitors, focusing among East
      Asians.

PMID- 27866702
TI  - Elucidation of Percutaneously Accessible Lymph Nodes in Swine: A Large Animal
      Model for Interventional Lymphatic Research.
AB  - PURPOSE: To define percutaneously accessible, anatomically reproducible swine
      lymph nodes using magnetic resonance imaging, ultrasound, and ethiodized oil
      (Lipiodol; Guerbet, Bloomington, Indiana) lymphangiography. MATERIALS AND
      METHODS: Five adult female swine (Yorkshire, 50-60 kg) were used. Under general
      anesthesia, T1-weighted and T2-weighted, coronal and axial images of the entire
      swine were obtained. The animal's extrathoracic, extraperitoneal soft tissues
      from the neck to the groins were examined with ultrasound. Lymph nodes >= 1 cm
      were marked before the animal was transferred to the angiography suite. Under
      ultrasound guidance, the nodes were accessed, and lymphangiograms were obtained.
      The imaging findings between the 3 modalities were correlated, and the lymph node
      drainage was mapped. RESULTS: Four lymph nodes/lymph node groups were identified
      that were reproducible in all 5 animals, > 1 cm and percutaneously accessible:
      submandibular node, superficial cervical lymph node group, subiliac node, and
      superficial inguinal lymph node group. Drainage of these nodes mirrored human
      anatomy. The abdominopelvic lymphatics formed a retroperitoneal cisterna chyli
      and drained cephalad via a thoracic duct. CONCLUSIONS: The swine exhibits
      reproducible lymphatic anatomy with at least 4 percutaneously accessible lymph
      nodes/lymph node groups. Based on these results, the swine may be a suitable
      large animal model for research into lymphatic interventions.

PMID- 27866703
TI  - Understanding the coherence of the severity effect and optimism phenomena:
      Lessons from attention.
AB  - Claims that optimism is a near-universal characteristic of human judgment seem to
      be at odds with recent results from the judgment and decision making literature
      suggesting that the likelihood of negative outcomes are overestimated relative to
      neutral outcomes. In an attempt to reconcile these seemingly contrasting
      phenomena, inspiration is drawn from the attention literature in which there is
      evidence that both positive and negative stimuli can have attentional privilege
      relative to neutral stimuli. This result provides a framework within which I
      consider three example phenomena that purport to demonstrate that people's
      likelihood estimates are optimistic: Wishful thinking; Unrealistic comparative
      optimism and Asymmetric belief updating. The framework clarifies the
      relationships between these phenomena and stimulates future research questions.
      Generally, whilst results from the first two phenomena appear reconcilable in
      this conceptualisation, further research is required in reconciling the third.

PMID- 27866704
TI  - Standardized Ultrasound Measurement of Subcutaneous Fat Patterning: High
      Reliability and Accuracy in Groups Ranging from Lean to Obese.
AB  - A recently standardized ultrasound technique for measuring subcutaneous adipose
      tissue (SAT) was applied to normal-weight, overweight and obese persons. Eight
      measurement sites were used: upper abdomen, lower abdomen, erector spinae, distal
      triceps, brachioradialis, lateral thigh, front thigh and medial calf. Fat
      compression was avoided. Fat patterning in 38 participants (body mass index: 18.6
      40.3 kgm-2; SAT thickness sums from eight sites: 12-245 mm) was evaluated using a
      software specifically designed for semi-automatic multiple thickness measurements
      in SAT (sound speed: 1450 m/s) that also quantifies embedded fibrous structures.
      With respect to ultrasound intra-observer results, the correlation coefficient
      rho = 0.999 (p < 0.01), standard error of the estimate = 1.1 mm and 95% of
      measurements were within +/-2.2 mm. For the normal-weight subgroup, the median
      measurement deviation was 0.43 mm (1.1% of mean thickness), and for the
      obese/overweight subgroup it was 0.89 mm (0.5%). The eight sites used here are
      suggested to represent inter-individual differences in SAT patterning. High
      measurement accuracy and reliability can be obtained in all groups, from lean to
      overweight and obese, provided that measurers are trained appropriately.

PMID- 27866705
TI  - Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange
      Factor DENND5A.
AB  - Epileptic encephalopathies are a catastrophic group of epilepsies characterized
      by refractory seizures and cognitive arrest, often resulting from abnormal brain
      development. Here, we have identified an epileptic encephalopathy additionally
      featuring cerebral calcifications and coarse facial features caused by recessive
      loss-of-function mutations in DENND5A. DENND5A contains a DENN domain, an
      evolutionarily ancient enzymatic module conferring guanine nucleotide exchange
      factor (GEF) activity to multiple proteins serving as GEFs for Rabs, which are
      key regulators of membrane trafficking. DENND5A is detected predominantly in
      neuronal tissues, and its highest levels occur during development. Knockdown of
      DENND5A leads to striking alterations in neuronal development. Mechanistically,
      these changes appear to result from upregulation of neurotrophin receptors,
      leading to enhanced downstream signaling. Thus, we have identified a link between
      a DENN domain protein and neuronal development, dysfunction of which is
      responsible for a form of epileptic encephalopathy.

PMID- 27866706
TI  - Colocalization of GWAS and eQTL Signals Detects Target Genes.
AB  - The vast majority of genome-wide association study (GWAS) risk loci fall in non
      coding regions of the genome. One possible hypothesis is that these GWAS risk
      loci alter the individual's disease risk through their effect on gene expression
      in different tissues. In order to understand the mechanisms driving a GWAS risk
      locus, it is helpful to determine which gene is affected in specific tissue
      types. For example, the relevant gene and tissue could play a role in the disease
      mechanism if the same variant responsible for a GWAS locus also affects gene
      expression. Identifying whether or not the same variant is causal in both GWASs
      and expression quantitative trail locus (eQTL) studies is challenging because of
      the uncertainty induced by linkage disequilibrium and the fact that some loci
      harbor multiple causal variants. However, current methods that address this
      problem assume that each locus contains a single causal variant. In this paper,
      we present eCAVIAR, a probabilistic method that has several key advantages over
      existing methods. First, our method can account for more than one causal variant
      in any given locus. Second, it can leverage summary statistics without accessing
      the individual genotype data. We use both simulated and real datasets to
      demonstrate the utility of our method. Using publicly available eQTL data on 45
      different tissues, we demonstrate that eCAVIAR can prioritize likely relevant
      tissues and target genes for a set of glucose- and insulin-related trait loci.

PMID- 27866707
TI  - A Functional Variant Associated with Atrial Fibrillation Regulates PITX2c
      Expression through TFAP2a.
AB  - The most significantly associated genetic locus for atrial fibrillation (AF) is
      in chromosomal region 4q25, where four independent association signals have been
      identified. Although model-system studies suggest that altered PITX2c expression
      might underlie the association, the link between specific variants and the
      direction of effect on gene expression remains unknown for all four signals. In
      the present study, we analyzed the AF-associated region most proximal to PITX2 at
      4q25. First, we identified candidate regulatory variants that might confer AF
      risk through a combination of mammalian conservation, DNase hypersensitivity, and
      histone modification from ENCODE and the Roadmap Epigenomics Project, as well as
      through in vivo analysis of enhancer activity in embryonic zebrafish. Within
      candidate regions, we then identified a single associated SNP, rs2595104, which
      displayed dramatically reduced enhancer activity with the AF risk allele. CRISPR
      Cas9-mediated deletion of the rs2595104 region and editing of the rs2595104 risk
      allele in human stem-cell-derived cardiomyocytes resulted in diminished PITX2c
      expression in comparison to that of the non-risk allele. This differential
      activity was mediated by activating enhancer binding protein 2 alpha (TFAP2a),
      which bound robustly to the non-risk allele at rs2595104, but not to the risk
      allele, in cardiomyocytes. In sum, we found that the AF-associated SNP rs2595104
      altered PITX2c expression via interaction with TFAP2a. Such a pathway could
      ultimately contribute to AF susceptibility at the PITX2 locus associated with AF.

PMID- 27866709
TI  - Disability, depression and suicide ideation in people with multiple sclerosis.
AB  - INTRODUCTION: Depressive symptoms occur frequently in people with Multiple
      Sclerosis (MS) and rates of suicide ideation are higher than the general
      population. There is evidence for a direct association between disability and
      depression, disability and suicide ideation, and depression and suicide ideation
      in MS. However, the relationship between all three, i.e. the mediating role of
      depression between disability and suicidal ideation, has not been investigated.
      Exploring this relationship could highlight risk factors, alerting clinicians to
      the need for timely intervention. METHOD: Seventy five people with progressive MS
      attending two out-patient clinics took part in this cross-sectional study.
      Participants completed the Beck Suicide Scale, Beck Depression Inventory,
      Multiple Sclerosis Impact Scale and Guy's Neurological Disability Scale. RESULTS:
      Depressive symptoms mediated the relationship between perceived and actual
      disability and suicide ideation. Different types of disability were associated
      with suicidality, including: 'tremors' and 'taking longer to do things'. A small
      sub-group of participants were identified who reported suicide ideation in the
      presence of only mild levels of depression. LIMITATIONS: There may be a sample
      bias in this study as all participants were attending out-patient clinics and
      receiving support which may not be available to everyone with MS. CONCLUSION: It
      is important for clinicians to screen regularly for both depression and suicide
      ideation, to be alert to specific types of disability for which a higher level of
      suicide ideation might be present and to consider the possibility of suicidal
      thoughts being present in people who show minimal or no depressive symptoms.

PMID- 27866710
TI  - Pulpal Tissue Inflammatory Reactions after Experimental Pulpal Exposure in Mice.
AB  - INTRODUCTION: The purpose of this study was to establish a stable experimental
      mice pulpal inflammatory model and to evaluate inflammatory reactions of pulpal
      tissue after pulpal exposure. METHODS: Pulpal inflammation was induced in 80
      C57BL/6 mice by occlusal exposure of the pulp of the maxillary first molar. The
      mice were sacrificed randomly at 0, 1, 6, 12, 24, 48, and 72 hours after pulpal
      exposure. Mice without pulpal exposure served as controls. Maxillary teeth were
      obtained and prepared for histologic analyses and real-time polymerase chain
      reaction analyses. RESULTS: As the duration of pulpal exposure increases, the
      inflammatory reaction is exacerbated. Within 6 to 12 hours after pulpal exposure,
      pulp tissues experienced red blood cell extravasation to the destruction of the
      odontoblast layer. After 24 hours, necrosis was observed in the pulpal tissue;
      until 72 hours, necrosis spread to the whole coronal pulpal tissue, and a large
      number of inflammatory cells were found in the radicular pulpal tissue. The
      results of histomorphologic scores have the same trend; samples from the 72-hour
      group possessed the highest score followed by samples from other groups (P <
      .01). The expression levels of inflammatory cytokines increased over the 72
      hours, and there was a high rate of inflammatory cytokine expression at 6 and 12
      hours after pulpal exposure. CONCLUSIONS: Our study represents a stable mice
      model for studying pulpal inflammation in vivo. Mouse pupal inflammation
      progresses rapidly, with dramatic changes evident in just a few hours.

PMID- 27866708
TI  - Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause
      Uncombable Hair Syndrome.
AB  - Uncombable hair syndrome (UHS), also known as "spun glass hair syndrome," "pili
      trianguli et canaliculi," or "cheveux incoiffables" is a rare anomaly of the hair
      shaft that occurs in children and improves with age. UHS is characterized by dry,
      frizzy, spangly, and often fair hair that is resistant to being combed flat.
      Until now, both simplex and familial UHS-affected case subjects with autosomal
      dominant as well as -recessive inheritance have been reported. However, none of
      these case subjects were linked to a molecular genetic cause. Here, we report the
      identification of UHS-causative mutations located in the three genes PADI3
      (peptidylarginine deiminase 3), TGM3 (transglutaminase 3), and TCHH
      (trichohyalin) in a total of 11 children. All of these individuals carry
      homozygous or compound heterozygous mutations in one of these three genes,
      indicating an autosomal-recessive inheritance pattern in the majority of UHS case
      subjects. The two enzymes PADI3 and TGM3, responsible for posttranslational
      protein modifications, and their target structural protein TCHH are all involved
      in hair shaft formation. Elucidation of the molecular outcomes of the disease
      causing mutations by cell culture experiments and tridimensional protein models
      demonstrated clear differences in the structural organization and activity of
      mutant and wild-type proteins. Scanning electron microscopy observations revealed
      morphological alterations in hair coat of Padi3 knockout mice. All together,
      these findings elucidate the molecular genetic causes of UHS and shed light on
      its pathophysiology and hair physiology in general.

PMID- 27866711
TI  - Discussion.

PMID- 27866712
TI  - Discussion.

PMID- 27866713
TI  - Twelve-year outcomes of laparoscopic adhesiolysis in patients with chronic
      abdominal pain: A randomized clinical trial.
AB  - BACKGROUND: Laparoscopic adhesiolysis as a therapy for chronic pain is still
      controversial, and long-term effects are not known; therefore, our aim was to
      evaluate long-term effects of laparoscopic adhesiolysis for the treatment of
      chronic abdominal pain believed to be related to intraperitoneal adhesions.
      METHODS: A total of 100 patients with abdominal pain attributed to adhesions were
      randomized to laparoscopic adhesiolysis or a placebo group with laparoscopy
      alone. Pain relief was assessed after 12-year follow-up. RESULTS: A total of 73%
      of patients fulfilled the long-term follow-up. Compared to the placebo group (n =
      31), patients in the adhesiolysis group (n = 42) were significantly less often
      pain-free (8 vs 13, P = .033, relative risk [RR] = 1.3) and to have a greater
      intake of analgesics (26 vs 16, P = .379, RR = 1.2, 95% confidence interval 0.8
      1.8). Moreover, the adhesiolysis group sought medical consultations more
      frequently (14 vs 6, P = .186, RR = 1.33, 95% confidence interval 0.9-1.9), and
      had an increased rate of additional operation (8 vs 1, P = .042, RR = 1.67, 95%
      confidence interval 1.208-2.318). Both groups had improved pain and quality-of
      life scores. CONCLUSION: This is the first, long-term, placebo-controlled trial
      regarding the use of laparoscopic adhesiolysis for treating chronic abdominal
      pain. Laparoscopic adhesiolysis was less beneficial than laparoscopy alone in the
      long term. Secondly, there appeared to be a powerful, long-lasting placebo effect
      of laparoscopy. Because adhesiolysis is associated with an increased risk of
      operative complications, avoiding this treatment may result in less morbidity and
      health care costs.

PMID- 27866714
TI  - Discussion.

PMID- 27866715
TI  - Normohormonal primary hyperparathyroidism is a distinct form of primary
      hyperparathyroidism.
AB  - BACKGROUND: Normohormonal primary hyperparathyroidism presents diagnostic and
      intraoperative challenges, and current literature is conflicting about
      management. We aim to better define normohormonal primary hyperparathyroidism in
      order to improve the care for these patients. METHODS: In the study, 516
      consecutive patients undergoing parathyroidectomy for primary hyperparathyroidism
      were divided into 2 groups: classic primary hyperparathyroidism (classic primary
      hyperparathyroidism, increased serum levels of calcium, and parathyroid hormone)
      and normohormonal primary hyperparathyroidism (hypercalcemia, normal serum levels
      of parathyroid hormone). We evaluated inter-group differences in presentation,
      gland weight, pathology, and complications. RESULTS: The normohormonal primary
      hyperparathyroidism group was comprised of 116 (22.5%) patients. Mean serum
      levels of parathyroid hormone and calcium were 62.1 pg/mL +/- 10.1 and 10.6 mg/dL
      +/- 0.63 in normohormonal primary hyperparathyroidism, and 142 +/- 89.0pg/mL and
      11.0 +/- 0.88 (both P < .01) for classic primary hyperparathyroidism.
      Nephrolithiasis was more common in normohormonal primary hyperparathyroidism.
      Multigland hyperplasia was more common in normohormonal primary
      hyperparathyroidism 23 (19.8%) vs 44 (11%; P = .04). Concordant imaging studies
      were less likely in normohormonal primary hyperparathyroidism (82 [73.2%] vs 337
      [87.1%; P < .01]), had a lesser total gland weight (531.8 mg +/- 680.0 vs 1,039.6
      mg +/- 1,237.3; P < .01), and lesser 2-week parathyroid hormone (32.5 pg/mL +/-
      18.95 vs 41.0 pg/mL +/- 27.8; P = .01). There was no difference in
      hypoparathyroidism (parathyroid hormone <15 pg/mL; P = .93) at 2 weeks
      postoperatively. CONCLUSION: Normohormonal primary hyperparathyroidism represents
      22.5% of our primary hyperparathyroidism population, which is greater than
      reported previously. It is a distinct disease process from classic primary
      hyperparathyroidism in presentation, imaging, and operative findings. More
      hyperplasia and a lesser gland weight make it challenging to resect the ideal
      amount of tissue. Studies with long-term follow-up are needed to determine
      optimal operative management.

PMID- 27866717
TI  - Adrenocortical carcinoma with inferior vena cava tumor thrombus.
AB  - BACKGROUND: The safety, efficacy, and prognostic implications of resection of
      adrenocortical carcinoma with inferior vena cava tumor thrombus are poorly
      described. METHODS: A retrospective review was performed during a 30-year period
      on patients who underwent resection of locally advanced, nonmetastatic
      adrenocortical carcinoma. We compared patients with and without inferior vena
      cava tumor thrombus, examining perioperative characteristics, completeness of
      resection, mortality, and survival. RESULTS: We identified 65 patients who
      underwent resection of locally advanced (T4N0 and T4N1) adrenocortical carcinoma
      (28 patients with inferior vena cava tumor thrombus, 37 noninferior vena cava
      tumor thrombus). Rate of complete resection, adjuvant chemotherapy, and short
      term postoperative morbidity was similar between groups. Overall survival was
      similar at 12-months. At 24 months overall survival was less in the inferior vena
      cava tumor thrombus group (59% vs 30%, P = .04). Differential survival through 60
      month follow-up favored the noninferior vena cava tumor thrombus group (36% vs
      0%, P = .001). Subgroup analysis including only patients with complete resection
      demonstrates similar survival at 24-months but at 36-months survival favored the
      noninferior vena cava tumor thrombus patients (65% vs 29%, P = .047) and this
      continued through 60 months (40% vs 0%, P = .049). CONCLUSION: Attempt at
      complete resection of adrenocortical carcinoma with inferior vena cava tumor
      thrombus seems justified particularly as short-term safety and survival are
      similar to patients without inferior vena cava tumor thrombus. However, survival
      beyond 36-months is limited in patients with inferior vena cava tumor thrombus.
      Patients being evaluated for resection in the setting of inferior vena cava tumor
      thrombus should be selected carefully.

PMID- 27866716
TI  - Can we consider immediate complications after thyroidectomy as a quality metric
      of operation?
AB  - BACKGROUND: Permanent recurrent laryngeal nerve palsy and hypoparathyroidism are
      2 major complications after thyroid operation. Assuming that the rate of
      immediate complications can predict the permanent complication rate, some authors
      consider these complications as a valid metric for assessing the performance of
      individual surgeons. This study aimed to determine the correlation between rates
      of immediate and permanent complications after thyroidectomy at the surgeon
      level. METHODS: We conducted a prospective, cross-sectional study in 5 academic
      hospitals between April 2008 and December 2009. The correlation between the rates
      of immediate and permanent complications for each of the 22 participating
      surgeons was calculated using the Pearson correlation test (r). RESULTS: The
      study period included 3,605 patients. There was a fairly good correlation between
      rates of immediate and permanent recurrent laryngeal nerve palsy (r = 0.70, P =
      .004), but no correlation was found for immediate and permanent
      hypoparathyroidism (r = 0.18, P = .427). CONCLUSION: The immediate
      hypoparathyroidism rate does not reflect the permanent hypoparathyroidism rate.
      Consequently, immediate hypoparathyroidism should not be used to assess the
      quality of thyroidectomy or to monitor the performance of surgeons.

PMID- 27866718
TI  - Mutational analysis of metastatic lymph nodes from papillary thyroid carcinoma in
      adult and pediatric patients.
AB  - BACKGROUND: Limited data are available on the analysis of somatic mutations in
      metastatic lymph nodes in adult and pediatric patients with papillary thyroid
      carcinomas. METHODS: A total of 92, microdissected, formalin-fixed, paraffin
      embedded tissue specimens from 39 patients were analyzed for the presence of
      somatic mutations utilizing the ThyGenX next-generation sequencing test. RESULTS:
      Somatic mutations were detected in 67% of papillary thyroid carcinoma specimens.
      The majority of patients with synchronous and all 6 patients with radioactive
      iodine-resistant (metachronous) metastatic lymph nodes contained BRAF mutations.
      Four patients had mutations detected in their metastatic lymph nodes that were
      not detected in their primary tumors. For the most part, BRAF mutations were seen
      in adults, and RAS mutations were seen in children. CONCLUSION: Findings of
      different mutations in metastatic lymph nodes compared with the primary papillary
      thyroid carcinomas are probably the result of tumor heterogeneity. The presence
      of the BRAF mutation in metastatic lymph nodes might be responsible for the
      recurrence of papillary thyroid carcinomas and resistance to radioactive iodine
      therapy. The good prognosis observed in papillary thyroid carcinomas found in
      pediatric and young adult patients might be explained by the predominance of RAS
      rather than BRAF mutations.

PMID- 27866719
TI  - Endocrine surgery fellowship graduates past, present, and future: 8 years of
      early job market experiences and what program directors and trainees can expect.
AB  - BACKGROUND: Given the increasing number of endocrine surgery fellowship
      graduates, we investigated if expectations and job opportunities changed over
      time. METHODS: American Association of Endocrine Surgeons (AAES) fellowship
      graduates, surgery department chairs, and physician recruiters were surveyed.
      Univariate analysis was performed with JMP Pro 12 software. RESULTS: We
      identified 141 graduates from 2008-2015; survey response rate was 72% (n = 101).
      Compared to earlier graduates, fewer academic opportunities were available for
      the recent graduates who intended to join them (P = .001). Unlike earlier
      graduates, recent graduates expected to also perform elective general surgery,
      which ultimately represented a greater percentage of their practices (both P <
      .05). Interview offers increased for recent graduates, but job offers decreased.
      Overall, 84% of graduates matched their intended practice type and 98% reported
      being satisfied. Reponses from graduates, department chairs, and physician
      recruiters highlighted opportunities to improve mentor involvement, job search
      strategies, and online job board utilization. CONCLUSION: The endocrine surgery
      job market has diversified resulting in more graduates entering nonacademic
      practices and performing general surgery. This rapid evolution supports future
      analyses of the job market and opportunities for job creation. Almost every
      graduate reported job satisfaction, which encourages graduates to consider
      joining both academic and nonacademic practices equally.

PMID- 27866720
TI  - Discussion.

PMID- 27866721
TI  - Discussion.

PMID- 27866722
TI  - Effectiveness of traffic-related elements in tree bark and pollen abortion rates
      for assessing air pollution exposure on respiratory mortality rates.
AB  - The majority of epidemiological studies correlate the cardiorespiratory effects
      of air pollution exposure by considering the concentrations of pollutants
      measured from conventional monitoring networks. The conventional air quality
      monitoring methods are expensive, and their data are insufficient for providing
      good spatial resolution. We hypothesized that bioassays using plants could
      effectively determine pollutant gradients, thus helping to assess the risks
      associated with air pollution exposure. The study regions were determined from
      different prevalent respiratory death distributions in the Sao Paulo
      municipality. Samples of tree flower buds were collected from twelve sites in
      four regional districts. The genotoxic effects caused by air pollution were
      tested through a pollen abortion bioassay. Elements derived from vehicular
      traffic that accumulated in tree barks were determined using energy-dispersive X
      ray fluorescence spectrometry (EDXRF). Mortality data were collected from the
      mortality information program of Sao Paulo City. Principal component analysis
      (PCA) was applied to the concentrations of elements accumulated in tree barks.
      Pearson correlation and exponential regression were performed considering the
      elements, pollen abortion rates and mortality data. PCA identified five factors,
      of which four represented elements related to vehicular traffic. The elements Al,
      S, Fe, Mn, Cu, and Zn showed a strong correlation with mortality rates (R2>0.87)
      and pollen abortion rates (R2>0.82). These results demonstrate that tree barks
      and pollen abortion rates allow for correlations between vehicular traffic
      emissions and associated outcomes such as genotoxic effects and mortality data.

PMID- 27866724
TI  - Spatial and temporal microbial pollution patterns in a tropical estuary during
      high and low river flow conditions.
AB  - Spatial and temporal patterns of coastal microbial pollution are not well
      documented. Our study examined these patterns through measurements of fecal
      indicator bacteria (FIB), nutrients, and physiochemical parameters in Hilo Bay,
      Hawai'i, during high and low river flow. >40% of samples tested positive for the
      human-associated Bacteroides marker, with highest percentages near rivers. Other
      FIB were also higher near rivers, but only Clostridium perfringens concentrations
      were related to discharge. During storms, FIB concentrations were three times to
      an order of magnitude higher, and increased with decreasing salinity and water
      temperature, and increasing turbidity. These relationships and high spatial
      resolution data for these parameters were used to create Enterococcus spp. and C.
      perfringens maps that predicted exceedances with 64% and 95% accuracy,
      respectively. Mapping microbial pollution patterns and predicting exceedances is
      a valuable tool that can improve water quality monitoring and aid in visualizing
      FIB hotspots for management actions.

PMID- 27866723
TI  - Association between ambient particulate matter exposure and semen quality in
      Wuhan, China.
AB  - BACKGROUND: Health effects of exposure to particulate matter (PM) on male
      reproductive health remain unclear. Only a limited number of studies have
      investigated the effects of PM2.5 or PM10 exposure on semen quality, and the
      results were largely inconsistent. OBJECTIVES: To quantitatively assess the
      exposure-response association between PM exposure and semen quality in Chinese
      men who were exposed to a wide concentration range of PM. METHODS: We
      investigated 1759 men from Wuhan, China, who were partners of women undergoing
      assisted reproductive technology procedures, and had semen examined at least once
      between 2013 and 2015. Individual PM2.5 and PM10 exposures during 0-90, 0-9, 10
      14 and 70-90days before each semen examination (corresponding to the entire and
      three key periods of sperm development, respectively) were retrospectively
      estimated by inverse distance weighting interpolation. Linear mixed models were
      used to assess exposure-response relations of PM exposure with sperm
      concentration, count and motility. RESULTS: PM2.5 exposure during 0-90 lag days
      ranged from 27.3 to 172.4MUg/m3. It was linearly and inversely associated with
      sperm concentration (beta: -0.20; 95% CI: -0.34, -0.07) and count (-0.22; -0.35, 
      0.08). For the three key exposure periods, only PM2.5 exposure during the 70-90
      lag days was significantly associated with sperm concentration (-0.12; -0.22, 
      0.03) and count (-0.12; -0.21, -0.02). Sensitivity analyses for a subgroup
      (n=1146) excluding subjects with abnormal sperm concentration, count or motility
      yielded similar results. Compared with PM2.5, we found generally similar
      associations for PM10 exposure in relation to sperm concentration and count,
      except that the associations appeared to be nonlinear with inverted J-shaped
      relationships. Neither PM2.5 nor PM10 exposure was significantly associated with
      sperm motility (all p>0.05). CONCLUSIONS: Our results suggest that ambient PM
      exposure during sperm development adversely affects semen quality, in particular
      sperm concentration and count.

PMID- 27866725
TI  - Common attributes of high/low performing general surgery programs as they relate
      to QE/CE pass rates.
AB  - PURPOSE: This comparative study aims to identify the differences between high and
      low performing programs as defined by their ABS board pass rates. METHODS: We
      identified programs in the top 5% (TP) and lower 5% (LP) for 1st time QE/CE pass
      rates during the study period with resident and program related variables. All
      data was pooled and analyzed. RESULTS: TP had more U.S. graduates, higher average
      USMLE Step 1/2 scores, and all residents took the exam within a year of
      graduation. TP were more likely to rotate at a Level 1 trauma center, spent more
      time with simulation, and had numerous fellowship programs. They ascribed their
      success to mock oral exams, mature curricula, and group educational activities.
      Graduates of TP chose general surgery twice as often (40% vs 19%). CONCLUSIONS:
      Program related factors (Level 1 trauma, excellent didactics, higher number of
      fellowships, increased group educational activities, higher percentage of
      graduates into general surgery) are associated with TP. Our data suggests there
      may be modifiable program related variables that positively impact QE/CE pass
      rates.

PMID- 27866726
TI  - Trends in mastectomy and reconstruction for breast cancer; a twelve year
      experience from a tertiary care center.
AB  - BACKGROUND: Many surgical options exist for breast cancer, including breast
      conserving therapy (BCT), mastectomy with reconstruction (MAST+RECON) or without
      reconstruction (MAST). Long-term results regarding oncologic outcomes are few and
      primarily retrospective studies. METHODS: A retrospective review of a
      prospectively collected database of patients undergoing breast surgery for breast
      cancer from 2002 to 2014 was performed. Patients were separated into 3 time
      periods for analysis: 2002 to 2005, 2006 to 2009, and 2010 to 2014. Recurrence
      outcomes were compared at 4 years between MAST+RECON patients. RESULTS: Two
      thousand seventy-six patients were identified: 61.2% underwent BCT, 19.7% had
      MAST, and 19.1% had MAST+RECON. BCT patients were older and had smaller tumors.
      MAST+RECON increased in prevalence, whereas BCT decreased. Implant-based
      reconstruction and conservative mastectomy rates increased over the study period.
      Four-year local recurrence-free rates were similar in nipple-sparing and skin
      sparing mastectomy groups. CONCLUSIONS: BCT usage has decreased, trending toward
      immediate, nipple-sparing mastectomy, implant-based reconstruction. Surgeons
      should be aware of trends to optimally offer patients their surgical options.

PMID- 27866727
TI  - Who did the case? Perceptions on resident operative participation.
AB  - BACKGROUND: The ACGME case log is one of the primary metrics used to determine
      resident competency; it is unclear if this is an accurate reflection of the
      residents' role and participation. METHODS: Residents and faculty were
      independently administered 16-question surveys following each case over a three
      week period. The main outcome was agreement between resident and faculty on
      resident role and percent of the case performed by the resident. RESULTS: Matched
      responses were collected for 87 cases. Agreement on percent performed occurred in
      61% of cases, on role in 63%, and on both in 47%. Disagreement was more often due
      to resident perception they performed more of the case. Faculty with <10 years
      experience were more likely to have disagreement compared to faculty with >=10
      years (p = 0.009). CONCLUSIONS: There was a high degree of disagreement between
      faculty and residents regarding percent of the case performed and role. Accurate
      understanding of participation and competency is vital for accrediting
      institutions and for resident self-assessment meriting further study of the
      causes for this disagreement to improve training and evaluation.

PMID- 27866728
TI  - What is new in 2015 in dysimmune neuropathies?
AB  - This review discusses and summarizes the concept of nodopathies, the diagnostic
      features, investigations, pathophysiology, and treatment options of chronic
      inflammatory demyelinating polyradiculoneuropathy, and gives updates on other
      inflammatory and dysimmune neuropathies such as Guillain-Barre syndrome, sensory
      neuronopathies, small-fiber-predominant ganglionitis, POEMS syndrome,
      neuropathies associated with IgM monoclonal gammopathy and multifocal motor
      neuropathy. This field of research has contributed to the antigenic
      characterization of the peripheral motor and sensory functional systems, as well
      as helping to define immune neuropathic syndromes with widely different clinical
      presentation, prognosis and response to therapy.

PMID- 27866730
TI  - Hereditary neuropathies: An update.
AB  - Hereditary neuropathies are the most common inherited neuromuscular diseases.
      Charcot-Marie-Tooth (CMT) disease represents the most common form with an average
      prevalence ranging from 1/2500 to 1/1200, depending on the studies. To date and
      with the advances of the latest generation sequencing, more than 80 genes have
      been identified. Although the common clinical phenotype comprises a progressive
      distal muscle weakness and sensory loss, foot deformities and decreased or absent
      tendon reflexes, clinical and electrophysiological phenotypes exhibit great
      variability. Moreover, atypical phenotypes are arising, overlapping with spastic
      paraplegia, hereditary sensory neuropathies or amyotrophic lateral sclerosis. The
      causative genes are involved in various biological processes such as myelin
      development and maintenance, biosynthesis and degradation of proteins, neuronal
      structural maintenance, axonal transport, endocytosis, membrane dynamics, ion
      channel function and the mitochondrial network. An accurate genetic diagnosis is
      important for appropriate genetic counselling and treatment options. Therapeutic
      advances, particularly small interfering RNA therapy, are encouraging in
      hereditary transthyretin amyloid neuropathy.

PMID- 27866729
TI  - Molecular imaging in the diagnosis of Alzheimer's disease and related disorders.
AB  - INTRODUCTION: The diagnosis of Alzheimer's disease (AD) and its related disorders
      rely on clinical criteria. There is, however, a large clinical overlap between
      the different neurodegenerative diseases affecting cognition and, frequently,
      there are diagnostic uncertainties with atypical clinical presentations. Current
      clinical practices can now regularly use positron emission tomography (PET) and
      single-photon emission computed tomography (SPECT) molecular imaging to help
      resolve such uncertainties. The Neurology Group of the French Society of Nuclear
      Medicine and Federations of Memory, Resources and Research Centers have
      collaborated to establish clinical guidelines to determine which molecular
      imaging techniques to use when seeking a differential diagnosis between AD and
      other neurodegenerative disorders affecting cognition. STATE OF KNOWLEDGE:
      According to the current medical literature, the potential usefulness of
      molecular imaging to address the typical clinical criteria in common forms of AD
      remains modest, as typical AD presentations rarely raise questions of
      differential diagnoses with other neurodegenerative disorders. However, molecular
      imaging could be of significant value in the diagnosis of atypical
      neurodegenerative disorders, including early onset, rapid cognitive decline,
      prominent non-amnestic presentations involving language, visuospatial,
      behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic
      presentations in other non-AD dementias. CONCLUSION AND PERSPECTIVE: The clinical
      use of molecular imaging should be recommended for assessing cognitive
      disturbances particularly in patients with early clinical onset (before age 65)
      and atypical presentations. However, diagnostic tools should always be part of
      the global clinical approach, as an isolated positive result cannot adequately
      establish a diagnosis of any neurodegenerative disorder.

PMID- 27866731
TI  - Guillain-Barre syndrome: 100 years on.
AB  - The Guillain-Barre syndrome is associated with acute polyradiculoneuritis for
      almost one century. Its spectrum has considerably been enlarged since its first
      description. It now includes pure motor or sensory syndromes, focal forms,
      demyelinating and axonal neurophysiological features that characterise
      excitability dysfunctions, and immunological differentiations. We can hope that
      this improved classification will facilitate development of treatment innovations
      for a condition that is still a life-threatening condition with a severe
      functional prognosis in a significant proportion of cases.

PMID- 27866732
TI  - Impact of a direct-admission stroke pathway on delays of admission, care, and
      rates of intravenous thrombolysis.
AB  - INTRODUCTION: This study examined the impact of a "direct potential thrombolysis"
      pathway with direct admission to a neurological stroke unit (SU) on delays of
      admission, stroke care and proportion of patients with ischemic stroke (IS)
      treated with intravenous (IV) rtPA. METHODS: This prospective study included all
      patients admitted in the intensive SU for potential thrombolysis over a 2-month
      period. Data collected included the time of symptom onset, mode of transport,
      National Institutes of Health Stroke Scale (NIHSS) score on arrival, delays of
      care, delays of imaging and modalities, diagnosis and therapeutic data. RESULTS:
      During the 2-month study period, 81 patients (mean age of 65 years) were included
      in the study. The Emergency Medical Services (EMS) were involved in 86% of
      admissions, with a median delay of admission of 1h48 and access within 4.5h in
      84% of cases. Every patient underwent immediate neurovascular assessment and
      imaging examination, which was a MRI in 80% of cases. Only 70% of patients had a
      final diagnosis of stroke. Intravenous rtPA therapy was administered to 26
      patients (32%), and 58% of patients with IS. The median door-to-needle time delay
      was 63min. CONCLUSION: A direct 'potential thrombolysis' pathway, based on EMS
      and located in the SU, can result in earlier admission, reaching the recommended
      care delay, and a large proportion (58%) of IS patients receiving rtPA therapy.
      On the other hand, the proportion of patients with stroke mimics is high, thereby
      increasing the chances of intermittent periods of saturation of this specific
      pathway.

PMID- 27866733
TI  - Review of the literature: Articles published in the last five years that have
      changed my daily practice.
AB  - Over the last five years, the management of peripheral neuropathies has become
      structured by the publication of recognized diagnostic criteria for inflammatory
      neuropathies and the elaboration of a function score, the R-ODS, used to evaluate
      the progression of these neuropathies. The concept of nodo-paranodopathy has
      enriched the concept of peripheral neuropathies, over-riding the classical
      mechanisms of axonal and demyelinating mechanisms. The structures of the nodes of
      Ranvier, gangliosides, contractin and neurofascin are preferential targets for
      auto-antibodies responsible for dysimmune neuropathies. Concerning treatments,
      immunosuppressors have demonstrated their efficacy for the treatment of anti-MAG
      neuropathies. Corticosteroid treatments are also in the limelight, demonstrating
      a different response profile than intravenous immunoglobulins for CIDP. But the
      most remarkable therapeutic progress has been made in the domain of hereditary
      neuropathies. The first trial versus placebo produced positive results in CMT1a.
      Finally, the era of genetic therapy appears to have come to fruition with the
      interfering RNA trial for familial amyloid neuropathies.

PMID- 27866736
TI  - Assessing the transport of PAH in the surficial sediment layer by passive sampler
      approach.
AB  - A new method based on passive samplers has been developed to assess the diffusive
      flux of fluorene, fluoranthene and pyrene in the sediment bed and across the
      sediment-water interface. The dissolved compound concentration gradient in the
      sediment in the vertical direction was measured at the outlet of a storm water
      pond by using polyethylene strips as passive samplers. Simultaneously, the
      dissipation of a set of tracer compounds preloaded in the passive samplers was
      measured to estimate the effective diffusion coefficients of the pollutants in
      the sediment. Both measurements were used to evaluate the diffusive flux of the
      compounds according to Fick's first law. The diffusive fluxes of the 3 studied
      compounds have been estimated with a centimetre-scale resolution in the upper
      44cm of the sediment. According to the higher compound diffusion coefficient and
      the steeper concentration gradient in the surficial sediment layer, the results
      show that the net flux of compounds near the sediment interface (1cm depth) is on
      average 500 times higher than in the deep sediment, with average fluxes at 1cm
      depth on the order of 5, 0.1 and 0.1ng/m2/y for fluorene, fluoranthene and
      pyrene, respectively.

PMID- 27866734
TI  - Comparing Variability, Severity, and Persistence of Depressive Symptoms as
      Predictors of Future Stroke Risk.
AB  - OBJECTIVE: Numerous studies show that depressive symptoms measured at a single
      assessment predict greater future stroke risk. Longer-term symptom patterns, such
      as variability across repeated measures or worst symptom level, might better
      reflect adverse aspects of depression than a single measurement. This prospective
      study compared five approaches to operationalizing depressive symptoms at annual
      assessments as predictors of stroke incidence. DESIGN: Cohort followed for
      incident stroke over an average of 6.4 years. SETTING: The Adult Changes in
      Thought cohort follows initially cognitively intact, community- dwelling older
      adults from a population base defined by membership in Group Health, a Seattle
      based nonprofit healthcare organization. PARTICIPANTS: 3,524 individuals aged 65
      years and older. MEASUREMENTS: We identified 665 incident strokes using ICD
      codes. We considered both baseline Center for Epidemiologic Studies-Depression
      scale (CES-D) score and, using a moving window of three most recent annual CES-D
      measurements, we compared most recent, maximum, average, and intra-individual
      variability of CES-D scores as predictors of subsequent stroke using Cox
      proportional hazards models. RESULTS: Greater maximum (hazard ratio [HR]: 1.18;
      95% CI: 1.07-1.30), average (HR: 1.20; 95% CI: 1.05-1.36) and intra-individual
      variability (HR: 1.15; 95% CI: 1.06-1.24) in CES-D were each associated with
      elevated stroke risk, independent of sociodemographics, cardiovascular risks,
      cognition, and daily functioning. Neither baseline nor most recent CES-D was
      associated with stroke. In a combined model, intra-individual variability in CES
      D predicted stroke, but average CES-D did not. CONCLUSIONS: Capturing the dynamic
      nature of depression is relevant in assessing stroke risk. Fluctuating depressive
      symptoms may reflect a prodrome of reduced cerebrovascular integrity.

PMID- 27866735
TI  - Metal exposures from aluminum cookware: An unrecognized public health risk in
      developing countries.
AB  - Removing lead from gasoline has resulted in decreases in blood lead levels in
      most of the world, but blood lead levels remain elevated in low and middle-income
      countries compared to more developed countries. Several reasons for this
      difference have been investigated, but few studies have examined the potential
      contribution from locally-made aluminum cookware. In a previous study of cookware
      from a single African country, Cameroon, artisanal aluminum cookware that is made
      from scrap metal released significant quantities of lead. In this study, 42
      intact aluminum cookware items from ten developing countries were tested for
      their potential to release lead and other metals during cooking. Fifteen items
      released >=1 microgram of lead per serving (250mL) when tested by boiling with
      dilute acetic acid for 2h. One pot, from Viet Nam, released 33, 1126 and 1426
      micrograms per serving in successive tests. Ten samples released >1 microgram of
      cadmium per serving, and fifteen items released >1 microgram of arsenic per
      serving. The mean exposure estimate for aluminum was 125mg per serving, more than
      six times the World Health Organization's Provisional Tolerable Weekly Intake of
      20mg/day for a 70kg adult, and 40 of 42 items tested exceeded this level. We
      conducted preliminary assessments of three potential methods to reduce metal
      leaching from this cookware. Coating the cookware reduced aluminum exposure per
      serving by >98%, and similar reductions were seen for other metals as well.
      Potential exposure to metals by corrosion during cooking may pose a significant
      and largely unrecognized public health risk which deserves urgent attention.

PMID- 27866737
TI  - Enhanced nitrogen loss from rivers through coupled nitrification-denitrification
      caused by suspended sediment.
AB  - Present-day estimations of global nitrogen loss (N-loss) are underestimated.
      Commonly, N-loss from rivers is thought to be caused by denitrification only in
      bed-sediments. However, coupled nitrification-denitrification occurring in
      overlying water with suspended sediments (SPS) where oxic and anoxic/low oxygen
      zones may coexist is ignored for N-loss in rivers. Here the Yellow and Yangtze
      Rivers were taken as examples to investigate the effect of SPS, which exists in
      many rivers of the world, on N loss through coupled nitrification-denitrification
      with nitrogen stable (15N) isotopic tracer simulation experiments and in-situ
      investigation. The results showed even when SPS was surrounded by oxic waters,
      there were redox conditions that transitioned from an oxic surface layer to
      anoxic layer near the particle center, enabling coupled nitrification
      denitrification to occur around SPS. The production rate of 15N2 from 15NH4+-N
      (R15N2-production) increased with increasing SPS concentration ([SPS]) as a power
      function (R15N2-production=a.[SPS]b) for both the SPS-water and bed sediment-SPS
      water systems. The power-functional increase of nitrifying and denitrifying
      bacteria population with [SPS] accounted for the enhanced coupled nitrification
      denitrification rate in overlying water. SPS also accelerated denitrification in
      bed-sediment due to increased NO3- concentration caused by SPS-mediated
      nitrification. For these two rivers, 1gL-1 SPS will lead to N-loss enhancement by
      approximately 25-120%, and the enhancement increased with organic carbon content
      of SPS. Thus, we conclude that SPS in overlying water is a hot spot for nitrogen
      loss in river systems and current estimates of in-stream N-loss are
      underestimated without consideration of SPS; this may partially compensate for
      the current imbalance of global nitrogen inputs and sinks.

PMID- 27866738
TI  - Novel hydrolytic de-methylthiolation of the s-triazine herbicide prometryn by
      Leucobacter sp. JW-1.
AB  - s-Triazine herbicides have been widely used in recent decades and caused serious
      concern over contamination of groundwater, surface water and soil. A novel
      bacterial strain JW-1 was isolated from activated sludge and identified as
      Leucobacter sp. based on comparative morphology, physiological characteristics
      and comparison of the 16S rDNA gene sequence. JW-1 was capable of using
      methylthio-s-triazine prometryn as a sole source of carbon and energy in pure
      culture. Favorable conditions for prometryn degradation were found at pH7.0-9.0
      and temperature of 37-42 degrees C. The degradation half-life of prometryn at
      50mgL-1 was remarkably as short as 1.1h, and increased to 6.0h when the initial
      concentration increased to 400mgL-1. The strain JW-1 could degrade 100% of
      ametryn, 99% of simetryn, 41% of propazine, 43% of atrazine, 28% of simazine, 12%
      of terbutylhylazine, 10% of prometon and 13% of atraton at 50mgL-1 of each
      herbicide in 2days. Prometryn was converted to 2-hydroxypropazine and methanthiol
      via a novel hydrolysis pathway. 2-Hydroxypropazine was then transformed to N
      isopropylammelide and the final product cyanuric acid via two sequential
      deamination reactions. In addition to biodegradation by Leucobacter sp. JW-1, the
      hydrolytic de-methylthiolation would be valuable in biocatalysis.

PMID- 27866740
TI  - Metabolomics evaluation of the in vivo toxicity of bromoacetonitriles: One class
      of high-risk nitrogenous disinfection byproducts.
AB  - Bromoacetonitriles (BANs), one class of nitrogenous disinfection byproducts (N
      DBPs), have frequently been detected in drinking water. The cytotoxicity and
      genotoxicity of BANs have been demonstrated in mammalian cells. However, a
      systematic study of the in vivo toxicity of BANs is rare. In this study,
      metabolomics combined with histopathology and oxidative stress analysis were used
      to evaluate the toxicity of BANs in mice. The results indicated that BAN exposure
      induced liver and kidney injury in mice. Furthermore, the superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) activities decreased, and the level of
      malonaldehyde (MDA) increased in mice livers due to BANs exposure, which
      indicated that hepatic oxidative stress was induced. These toxicities increased
      with an increasing number of bromine at the alpha carbon. In addition, BAN
      exposure disrupted the metabolic pathways of amino acid, energy and lipid
      metabolism in mice. Our results provide evidence for the comprehensive omics
      endpoints of the in vivo toxicity of BANs.

PMID- 27866739
TI  - An integrated approach for identifying priority contaminant in the Great Lakes
      Basin - Investigations in the Lower Green Bay/Fox River and Milwaukee Estuary
      areas of concern.
AB  - Environmental assessment of complex mixtures typically requires integration of
      chemical and biological measurements. This study demonstrates the use of a
      combination of instrumental chemical analyses, effects-based monitoring, and bio
      effects prediction approaches to help identify potential hazards and priority
      contaminants in two Great Lakes Areas of Concern (AOCs), the Lower Green Bay/Fox
      River located near Green Bay, WI, USA and the Milwaukee Estuary, located near
      Milwaukee, WI, USA. Fathead minnows were caged at four sites within each AOC
      (eight sites total). Following 4d of in situ exposure, tissues and biofluids were
      sampled and used for targeted biological effects analyses. Additionally, 4d
      composite water samples were collected concurrently at each caged fish site and
      analyzed for 132 analytes as well as evaluated for total estrogenic and
      androgenic activity using cell-based bioassays. Of the analytes examined, 75 were
      detected in composite samples from at least one site. Based on multiple analyses,
      one site in the East River and another site near a paper mill discharge in the
      Lower Green Bay/Fox River AOC, were prioritized due to their estrogenic and
      androgenic activity, respectively. The water samples from other sites generally
      did not exhibit significant estrogenic or androgenic activity, nor was there
      evidence for endocrine disruption in the fish exposed at these sites as indicated
      by the lack of alterations in ex vivo steroid production, circulating steroid
      concentrations, or vitellogenin mRNA expression in males. Induction of hepatic
      cyp1a mRNA expression was detected at several sites, suggesting the presence of
      chemicals that activate the aryl hydrocarbon receptor. To expand the scope beyond
      targeted investigation of endpoints selected a priori, several bio-effects
      prediction approaches were employed to identify other potentially disturbed
      biological pathways and related chemical constituents that may warrant future
      monitoring at these sites. For example, several chemicals such as
      diethylphthalate and naphthalene, and genes and related pathways, such as
      cholinergic receptor muscarinic 3 (CHRM3), estrogen receptor alpha1 (esr1),
      chemokine ligand 10 protein (CXCL10), tumor protein p53 (p53), and monoamine
      oxidase B (Maob), were identified as candidates for future assessments at these
      AOCs. Overall, this study demonstrates that a better prioritization of
      contaminants and associated hazards can be achieved through integrated evaluation
      of multiple lines of evidence. Such prioritization can guide more comprehensive
      follow-up risk assessment efforts.

PMID- 27866741
TI  - Assessment of indoor air quality in office buildings across Europe - The OFFICAIR
      study.
AB  - The European project OFFICAIR aimed to broaden the existing knowledge regarding
      indoor air quality (IAQ) in modern office buildings, i.e., recently built or
      refurbished buildings. Thirty-seven office buildings participated in the summer
      campaign (2012), and thirty-five participated in the winter campaign (2012-2013).
      Four rooms were investigated per building. The target pollutants were twelve
      volatile organic compounds, seven aldehydes, ozone, nitrogen dioxide and
      particulate matter with aerodynamic diameter <2.5MUm (PM2.5). Compared to other
      studies in office buildings, the benzene, toluene, ethylbenzene, and xylene
      concentrations were lower in OFFICAIR buildings, while the alpha-pinene and d
      limonene concentrations were higher, and the aldehyde, nitrogen dioxide and PM2.5
      concentrations were of the same order of magnitude. When comparing summer and
      winter, significantly higher concentrations were measured in summer for
      formaldehyde and ozone, and in winter for benzene, alpha-pinene, d-limonene, and
      nitrogen dioxide. The terpene and 2-ethylhexanol concentrations showed
      heterogeneity within buildings regardless of the season. Considering the average
      of the summer and winter concentrations, the acetaldehyde and hexanal
      concentrations tended to increase by 4-5% on average with every floor level
      increase, and the nitrogen dioxide concentration tended to decrease by 3% on
      average with every floor level increase. A preliminary evaluation of IAQ in terms
      of potential irritative and respiratory health effects was performed. The 5-day
      median and maximum indoor air concentrations of formaldehyde and ozone did not
      exceed their respective WHO air quality guidelines, and those of acrolein, alpha
      pinene, and d-limonene were lower than their estimated thresholds for irritative
      and respiratory effects. PM2.5 indoor concentrations were higher than the 24-h
      and annual WHO ambient air quality guidelines.

PMID- 27866742
TI  - Spatiotemporal patterns of paddy rice croplands in China and India from 2000 to
      2015.
AB  - Due to rapid population growth and urbanization, paddy rice agriculture is
      experiencing substantial changes in the spatiotemporal pattern of planting areas
      in the two most populous countries-China and India-where food security is always
      the primary concern. However, there is no spatially explicit and continuous rice
      planting information in either country. This knowledge gap clearly hinders our
      ability to understand the effects of spatial paddy rice area dynamics on the
      environment, such as food and water security, climate change, and zoonotic
      infectious disease transmission. To resolve this problem, we first generated
      annual maps of paddy rice planting areas for both countries from 2000 to 2015,
      which are derived from time series Moderate Resolution Imaging Spectroradiometer
      (MODIS) data and the phenology- and pixel-based rice mapping platform (RICE
      MODIS), and analyzed the spatiotemporal pattern of paddy rice dynamics in the two
      countries. We found that China experienced a general decrease in paddy rice
      planting area with a rate of 0.72 million (m) ha/yr from 2000 to 2015, while a
      significant increase at a rate of 0.27mha/yr for the same time period happened in
      India. The spatial pattern of paddy rice agriculture in China shifted
      northeastward significantly, due to simultaneous expansions in paddy rice
      planting areas in northeastern China and contractions in southern China. India
      showed an expansion of paddy rice areas across the entire country, particularly
      in the northwestern region of the Indo-Gangetic Plain located in north India and
      the central and south plateau of India. In general, there has been a
      northwesterly shift in the spatial pattern of paddy rice agriculture in India.
      These changes in the spatiotemporal patterns of paddy rice planting area have
      raised new concerns on how the shift may affect national food security and
      environmental issues relevant to water, climate, and biodiversity.

PMID- 27866743
TI  - A data-mining framework for exploring the multi-relation between fish species and
      water quality through self-organizing map.
AB  - The steep slopes of rivers can easily lead to large variations in river water
      quality during typhoon seasons in Taiwan, which may poses significant impacts on
      riverine eco-hydrological environments. This study aims to investigate the
      relationship between fish communities and water quality by using artificial
      neural networks (ANNs) for comprehending the upstream eco-hydrological system in
      northern Taiwan. We collected a total of 276 heterogeneous datasets with 8 water
      quality parameters and 25 fish species from 10 sampling sites. The self
      organizing feature map (SOM) was used to cluster, analyze and visualize the
      heterogeneous datasets. Furthermore, the structuring index (SI) was adopted to
      determine the relative importance of each input variable of the SOM and identify
      the indicator factors. The clustering results showed that the SOM could suitably
      reflect the spatial characteristics of fishery sampling sites. Besides, the
      patterns of water quality parameters and fish species could be distinguishably
      (visually) classified into three eco-water quality groups: 1) typical upstream
      freshwater fishes that depended the most on dissolved oxygen (DO); 2) typical
      middle-lower reach riverine freshwater fishes that depended the most on total
      phosphorus (TP) and ammonia nitrogen; and 3) low lands or pond (reservoirs)
      freshwater fishes that depended the most on water temperature, suspended solids
      and chemical oxygen demand. According to the results of the SI, the
      representative indicators of water quality parameters and fish species consisted
      of DO, TP and Onychostoma barbatulum. This grouping result suggested that the
      methodology can be used as a guiding reference to comprehensively relate ecology
      to water quality. Our methods offer a cost-effective alternative to more
      traditional methods for identifying key water quality factors relating to fish
      species. In addition, visualizing the constructed topological maps of the SOM
      could produce detailed inter-relation between water quality and the fish species
      of stream habitat units.

PMID- 27866744
TI  - Role of solution chemistry in the retention and release of graphene oxide
      nanomaterials in uncoated and iron oxide-coated sand.
AB  - Understanding the fate and transport including remobilization of graphene oxide
      nanomaterials (GONMs) in the subsurface would enable us to expedite their benign
      use and evaluate their environmental impacts and health risks. In this study, the
      retention and release of GONMs were investigated in water-saturated columns
      packed with uncoated sand (Un-S) or iron oxide-coated sand (FeS) at
      environmentally relevant solution chemistries (1-100mM KCl and 0.1-10mM CaCl2 at
      pH7 and 11). Our results showed that increasing ionic strength (IS) inhibited
      GONMs' transport, and the impact of K+ was less than Ca2+. The positively charged
      iron oxide coating on sand surfaces immobilized the negatively charged GONMs
      (pH7) in the primary minimum, yielding hyperexponential retention profiles
      particularly in Ca2+. A stepwise decrease in pore-water IS caused detachment of
      previously retained GONMs. The mass of GONMs released during each detachment step
      correlated positively with the difference in secondary minimum depth
      (DeltaPhimin2) at each IS, indicating that the released GONMs were retained in
      the secondary minimum. While most retained GONMs were re-entrained upon lowering
      pore-water IS in Un-S, decreasing IS only released limited GONMs in FeS, which
      were captured in the primary minimum. Introducing 1mM NaOH (pH11) released most
      retained GONMs in FeS; and average hydrodynamic diameters of the detached GONMs
      upon injecting NaOH were significantly smaller than those of GONMs in the
      influent and retentate, suggesting that NaOH induced GONMs disaggregation. Our
      findings advance current knowledge to better predict NMs' fate and transport
      under various solution chemistries such as during rainfall events or in the
      mixing zones between sea water and fresh water where transient IS changes
      drastically.

PMID- 27866745
TI  - Urbanization impact on sulfur content of groundwater revealed by the study of
      urban speleothem-like deposits: Case study in Paris, France.
AB  - Speleothem-like deposits that develop underground in urban areas are an archive
      of the environmental impact of anthropic activities that has been little studied
      so far. In this paper, the sulfate content in shallow groundwater from northern
      Paris (France) is compared with the sulfur content in two 300-year-old urban
      carbonate deposits that grew in a historical underground aqueduct. The present
      day waters of the aqueduct have very high sulfur and calcium contents, suggesting
      pollution from gypsum dissolution. However, geological gypsum levels are located
      below the water table. Sulfur content was measured by micro-X-ray fluorescence in
      these very S-rich carbonate deposits (0.5 to 1% of S). A twofold S increase
      during the second half of the 1800s was found in both samples. These dates
      correspond to two major periods of urbanization above the site. We discus three
      possible S sources: anthropic sources (industries, fertilizers...), volcanic
      eruptions and input within the water through gypsum brought for urbanization
      above the studied site (backfill with quarry waste) since the middle of the 19th
      century. For the younger second half of the studied section, S input from gypsum
      brought during urbanization was confirmed by the study of isotopic sulfur
      composition (delta34S=+15.20/00 at the top). For the oldest part, several sulfur
      peaks could be related to early industrial activity in Paris, that caused high
      local air pollution, as reported in historical archives but also to historical
      gypsum extraction. This study provides information on the origin and timing of
      the very high SO42- levels measured nowadays within the shallow groundwater, thus
      demonstrating the interest in using carbonate deposits in urban areas as a proxy
      for the history of urbanization or human activities and their impact on water
      bodies.

PMID- 27866746
TI  - How does elevated ozone reduce methane emissions from peatlands?
AB  - The effects of increased tropospheric ozone (O3) pollution levels on methane
      (CH4) emissions from peatlands, and their underlying mechanisms, remain unclear.
      In this study, we exposed peatland mesocosms from a temperate wet heath dominated
      by the sedge Schoenus nigricans and Sphagnum papillosum to four O3 treatments in
      open-top chambers for 2.5years, to investigate the O3 impacts on CH4 emissions
      and the processes that underpin these responses. Summer CH4 emissions, were
      significantly reduced, by 27% over the experiment, due to summer daytime (8hday
      1) O3 exposure to non-filtered air (NFA) plus 35ppb O3, but were not
      significantly affected by year-round, 24hday-1, exposure to NFA plus 10ppb or NFA
      plus 25ppb O3. There was no evidence that the reduced CH4 emissions in response
      to elevated summer O3 exposure were caused by reduced plant-derived carbon
      availability below-ground, because we found no significant effect of high summer
      O3 exposure on root biomass, pore water dissolved organic carbon concentrations
      or the contribution of recent photosynthate to CH4 emissions. Our CH4 production
      potential and CH4 oxidation potential measurements in the different O3 treatments
      could also not explain the observed CH4 emission responses to O3. However, pore
      water ammonium concentrations at 20cm depth were consistently reduced during the
      experiment by elevated summer O3 exposure, and strong positive correlations were
      observed between CH4 emission and pore water ammonium concentration at three peat
      depths over the 2.5-year study. Our results therefore imply that elevated
      regional O3 exposures in summer, but not the small increases in northern
      hemisphere annual mean background O3 concentrations predicted over this century,
      may lead to reduced CH4 emissions from temperate peatlands as a consequence of
      reductions in soil inorganic nitrogen affecting methanogenic and/or
      methanotrophic activity.

PMID- 27866747
TI  - Predicting readmission risk following coronary artery bypass surgery at the time
      of admission.
AB  - BACKGROUND: Reducing readmissions following hospitalization is a national
      priority. Identifying patients at high risk for readmission after coronary artery
      bypass graft surgery (CABG) early in a hospitalization would enable hospitals to
      enhance discharge planning. METHODS: We developed different models to predict 30
      day inpatient readmission to our institution in patients who underwent CABG
      between January 2010 and April 2013. These models used data available: 1) at
      admission, 2) at discharge 3) from STS Registry data. We used logistic regression
      and assessed the discrimination of each model using the c-index. The models were
      validated with testing on a different patient cohort who underwent CABG between
      May 2013 and September 2015. Our cohort included 1277 CABG patients: 1159 in the
      derivation cohort and 1018 in the validation cohort. RESULTS: The discriminative
      ability of the admission model was reasonable (C-index of 0.673). The c-indices
      for the discharge and STS models were slightly better. (C-index of 0.700 and
      0.714 respectively). Internal validation of the models showed a reasonable
      discriminative admission model with slight improvement with adding discharge and
      registry data (C-index of 0.641, 0.659 and 0.670 respectively). Similarly
      validation of the models on the validation cohort showed similar results (C-index
      of 0.573, 0.605 and 0.595 respectively). CONCLUSIONS: Risk prediction models
      based on data available early on admission are predictive for readmission risk.
      Adding registry data did not improved the performance of these models. These
      simplified models may be sufficient to identify patients at highest risk of
      readmission following coronary revascularization early in the hospitalization.

PMID- 27866748
TI  - Promus Premier versus Xience V and Taxus Liberte in contemporary United States
      practice (REWARDS premier registry).
AB  - BACKGROUND/PURPOSE: Drug-eluting stents (DES) reduce in-stent restenosis and
      repeat revascularization in comparison to bare metal stents. Individual DES vary,
      however, in regard to rates of restenosis and stent thrombosis; they also differ
      in regard to their platform and physical characteristics. The Promus Premier was
      designed to improve the performance of the Promus Element, with respect to
      conformability, trackability, and avoidance of longitudinal stent deformation;
      there is little published data, however, on clinical outcomes with Promus
      Premier. METHODS: We performed a registry study that compared 952 patients who
      underwent percutaneous coronary intervention with Promus Premier to 595 patients
      who received Taxus Liberte and 600 patients who received Xience V for a variety
      of indications. The primary endpoint was a composite of all-cause mortality,
      definite or probable stent thrombosis, myocardial infarction, and target vessel
      revascularization (TVR-MACE). Kaplan-Meier analysis and Cox proportional hazards
      regression were performed in order to compare the three stents in regard to
      outcomes at 1year. RESULTS: Procedural success was highest with Premier (99.4%)
      when compared to Xience V (98.0%) and Taxus Liberte (97.3%; p<0.001). Unadjusted
      survival analysis showed that TVR-MACE was less frequent with Premier in
      comparison to Taxus Liberte (p=0.003), and similar frequency in comparison to
      Xience V (p=0.16). Following multivariable adjustment, and using Xience V as the
      reference, there was only a borderline association of Promus Premier and lower
      rates of TVR-MACE (HR 0.69, 95% CI 0.45-1.04; p=0.075). CONCLUSION: Promus
      Premier demonstrates excellent procedural success rates and real-world outcomes
      that are similar to Xience V.

PMID- 27866749
TI  - Inter-population and inter-organ distribution of the main polyphenolic compounds
      of Epilobium angustifolium.
AB  - Rosebay willowherb (Epilobium angustifolium) contains large amounts of
      polyphenolic compounds, including tellimagrandin I-based oligomeric ellagitannins
      (ETs). The aim of this study was to assess the interpopulational and inter-organ
      variability of the polyphenol fingerprint of E. angustifolium. Seven ETs, 11
      flavonol glycosides and neochlorogenic acid were quantified by UHPLC-DAD-ESI-QqQ
      MS in the leaves, flowers and stem parts of plants from 10 populations. Total
      polyphenol content of leaves and flowers ranged from 150 to 200 mg/g dry wt, of
      which 90% was constituted by dimeric to heptameric ETs. Flowers contained, on
      average, 10% more oenothein B (dimeric ET) and 2 times less oenothein A (trimeric
      ET) than leaves. Tetrameric and pentameric ETs exhibited rather similar levels in
      leaves and flowers whereas hexameric and heptameric were 3-4 times more abundant
      in flowers than in leaves. Quercetin-3-O-rhamnoside, myricetin-3-O-rhamnoside and
      kaempferol-3-O-rhamnoside were specific to flower tissue and were absent from
      leaves. The inflorescence stem showed the highest content in total polyphenols
      with an average of 250 mg/g dry wt and contained remarkably large amounts of
      oenothein B and A. Polyphenol content steadily decreased along the inflorescence
      stem and reached its lowest level in the vegetative part of the stem. The
      interpopulational variability of most polyphenols was within a two- to threefold
      range across the 10 sampled populations. Myricetin-3-O-glucoside and myricetin-3
      O-glucuronide, however, showed a more population-specific distribution with
      concentrations varying from 0 to 2.3 mg/g dry wt. Finally, this study showed that
      the levels of oenothein B and A in the plant are not interdependent but that
      their relative abundance is constant within a population.

PMID- 27866751
TI  - Weight loss after bariatric surgery and periodontal changes: a 12-month
      prospective study.
AB  - BACKGROUND: Several longitudinal studies have explored the association of obesity
      and weight gain with periodontal disease. However, the effect of weight loss on
      periodontal tissues remains unclear. OBJECTIVE: To explore whether weight loss
      after bariatric surgery was associated with changes in periodontal measures over
      12 months. SETTING: Two public hospitals in Sao Paulo, Brazil. METHODS: We used
      data from 110 morbidly obese patients (body mass index [BMI]>40 kg/m2 or>=35
      kg/m2 with co-morbid conditions) who underwent bariatric surgery between April
      2011 and March 2013. Data on demographic factors, BMI, smoking habits, and
      glucose levels were extracted from medical records preoperatively and after 6 and
      12 months postsurgery. A full-mouth periodontal examination was conducted by
      trained examiners to assess probing pocket depth, clinical attachment loss, and
      bleeding on probing (BOP) at baseline and 6 and 12 months after surgery. Data
      were analyzed using linear mixed-effects models. RESULTS: BMI was not
      significantly related to the proportion of sites with BOP at baseline, but it was
      negatively associated with the rate of change in the proportion of sites with
      BOP. The greater the BMI loss, the higher the proportion of sites with BOP,
      particularly 6 months after surgery. However, BMI was not associated with
      baseline probing pocket depth and clinical attachment loss or rates of changes in
      these periodontal outcomes. CONCLUSION: The findings suggest that weight loss was
      associated with increased gingival bleeding, showing a peak at 6 months after
      bariatric surgery. Periodontal pocketing and attachment loss remained unchanged
      during the study period.

PMID- 27866752
TI  - Selling antimicrobials without prescription - Far beyond an administrative
      problem.
AB  - INTRODUCTION: Selling antibiotics without prescription is common in many
      countries; beyond the administrative restrictions, this practice is a risk for
      patients and society. The aim of the study was to evaluate the information
      provided by the staff of the pharmacy to a simulated patient requesting an
      antibiotic. MATERIAL AND METHODS: A prospective study was carried out in January
      2013 - February 2014 in the Health Region of Tarragona, in which a mystery
      shopper visited 220 pharmacies requesting an antibiotic to be sold. RESULTS: The
      actress was not asked about allergies in 73.9% of cases and never was asked about
      possible pregnancy. Recommendation to see a doctor was observed in 36.1% of
      cases. When antibiotics were not sold, the explanation provided by the staff was
      reasoned only in 9.9% of the cases. CONCLUSION: It is necessary and urgent to
      improve the training of pharmacists in dispensing antibiotics but also strengthen
      basic health knowledge among the population.

PMID- 27866750
TI  - Distinguishing hypothetical willingness from behavioral intentions to initiate
      HIV pre-exposure prophylaxis (PrEP): Findings from a large cohort of gay and
      bisexual men in the U.S.
AB  - RATIONALE: Much of the data on the acceptability of HIV Pre-Exposure Prophylaxis
      (PrEP) is based on willingness to take PrEP (i.e., hypothetical receptivity)
      rather than actual intentions (i.e., planned behavioral action) to do so.
      OBJECTIVE: We sought to examine differences between hypothetical willingness and
      behavioral intentions to begin PrEP in a national sample of gay and bisexual men
      (GBM) across the U.S. METHODS: We utilized data collected in 2015 to examine
      differences between those Unwilling (42.6% n = 375), Willing but not intending
      (41.4%, n = 365), and willing and Intending to take PrEP (15.9%, n = 140) in a
      multivariable, multinomial logistic regression. RESULTS: Men with less education
      had higher odds of Intending to take PrEP. Compared to men unsure about PrEP's
      efficacy, those who believed PrEP was at least 90% efficacious had higher odds of
      Intending to take PrEP. Those who saw themselves as appropriate candidates for
      PrEP had higher odds of Intending to take PrEP while those who saw themselves as
      inappropriate candidates for PrEP had lower odds of Intending to take PrEP in
      comparison to men unsure if they were appropriate candidates. Increased
      motivation for condom non-use because of perceived sexual pressure by partners
      was associated with higher odds of Intending to take PrEP. The groups did not
      differ by risk behavior nor recent STI diagnosis. CONCLUSIONS: Overall, the
      distinction between willingness and intentions to take PrEP was meaningful and
      may help explain disparities between PrEP acceptability and uptake. While much of
      the literature has focused on hypothetical willingness to take PrEP, these
      results highlight the importance of simultaneously assessing willingness and
      intentions when examining correspondence with uptake and developing interventions
      to increase PrEP uptake.

PMID- 27866753
TI  - Molecular epidemiology of carbapenemase-producing Enterobacteriaceae
      infection/colonisation in a hospital in Madrid.
AB  - INTRODUCTION: A description is presented on the molecular epidemiology of
      carbapenemase-producing enterobacteriaceae infection in a tertiary hospital.
      MATERIAL AND METHODS: A study was made on all the carbapenemase-producing
      enterobacteriaceae isolations obtained between February 2015 and March 2016 in
      the Hospital Universitario 12 de Octubre (Madrid). Phenotypic and molecular
      methods were used. RESULTS: A total of 7 bacterial species were identified, with
      the majority being Klebsiella pneumoniae (K. pneumoniae) (78.9%) and Enterobacter
      cloacae (E. cloacae) (16.4%). The resistance of K. pneumoniae and E. cloacae for
      carbapenems was 88.7 and 88.6% for ertapenem, 21.4 and 54.3% for imipenem, and
      20.8 and 34.3% for meropenem, respectively. The most frequent carbapenemase type
      was OXA-48 (91.1%) and VIM (71.4%) in E. cloacae. A total of 9K. pneumoniae
      clonal types were identified, including a majority pertaining to the sequence
      type ST11. In E. cloacae, 16 clonal types were identified. CONCLUSIONS: The
      current increase in carbapenemase-producing enterobacteriaceae is mainly due to
      the spread of OXA-48-producing K. pneumoniae.

PMID- 27866754
TI  - Cat bite wound infection.

PMID- 27866755
TI  - Evaluation of an automated room decontamination device using aerosolized
      peracetic acid.
AB  - Because manual cleaning is often suboptimal, there is increasing interest in use
      of automated devices for room decontamination. We demonstrated that an ultrasonic
      room fogging system that generates submicron droplets of peracetic acid and
      hydrogen peroxide eliminated Clostridium difficile spores and vegetative
      pathogens from exposed carriers in hospital rooms and adjacent bathrooms.

PMID- 27866756
TI  - Cuboid morphology of a basal anthropoid from the Eocene of China.

PMID- 27866757
TI  - Differential diagnosis of IgG4-related sialadenitis, primary Sjogren syndrome,
      and chronic obstructive submandibular sialadenitis.
AB  - Our aim was to differentiate IgG4-related sialadenitis, primary Sjogren syndrome,
      and chronic obstructive submandibular sialadenitis by analysing clinical,
      radiographic, and pathological features. Fifty-five patients, 50, and 50 were
      enrolled, respectively and their baseline characteristics and serological,
      sialographic, and pathological findings compared. The male:female ratio for IgG4
      related sialadenitis was 1:1.2 for primary Sjogren syndrome 1:15.7, and for
      chronic obstructive submandibular sialadenitis1:0.92. Numbers with enlarged
      salivary glands were 55, 16, and 50; with xerostomia 26, 48, and 0; with a
      history of allergy 26, 4, and 6, and with coexisting systemic disease 12, 19, and
      0 (p=0.14). Mean (SD) serum IgG4 concentrations were 109.1 (97.9), 4.9. (1.9)
      g/L, and 5.3 (1.6) g/L, p<0.001 in all cases. Sialography showed enlargement of
      the gland, dilatation of the duct, and slightly decreased secretory function in
      IgG4-related disease; obvious sialectasia and decreased secretory function in
      Sjogren syndrome; and dilatation of Wharton's duct and filling defects in
      obstructive sialadenitis. Histopathological examination showed lymphoplasmacytic
      infiltration with storiform fibrosis, lymphoplasmacytic inflammation and
      lymphoepithelial lesions, and dilatation of the duct with epithelial metaplasia
      in the three groups, respectively. The number of IgG4-positive plasma cells was
      123 (45)/HPF, 8 (3)/HPF, and 5 (4)/HPF, while the IgG4-/IgG-positive cell ratio
      was 71.7 (13.9)%, 4.6 (2.5)%, 18.9 (19.7)%, respectively (p<0.001). The three
      conditions have different clinical, radiographic, and pathological features that
      provide important clues to the differential diagnosis. Serological and
      histological tests are important, and comprehensive consideration is necessary.

PMID- 27866758
TI  - The influence of deprivation on malnutrition risk in outpatients with chronic
      obstructive pulmonary disease (COPD).
AB  - BACKGROUND & AIMS: The social gradient in chronic obstructive pulmonary disease
      (COPD) is considerable, but the influence of deprivation on common clinical risk
      factors such as malnutrition is unclear. This study aimed to explore the
      relationship between COPD disease-severity, deprivation and malnutrition.
      METHODS: 424 outpatients with a confirmed diagnosis of COPD were routinely
      screened for malnutrition risk using the 'Malnutrition Universal Screening Tool'
      ('MUST') while attending respiratory clinics across two hospitals; a large city
      hospital (site A) and a smaller community hospital (site B). Deprivation was
      assessed for each outpatient according to their address (postcode) using the
      English governments' index of multiple deprivation (IMD) and related to
      malnutrition risk. Each postcode was attributed to both an IMD score and IMD
      rank, where a higher IMD score and a lower IMD ranking indicated increased
      deprivation. RESULTS: Overall prevalence of malnutrition was 22% (95% CI 18-26%;
      9% medium risk, 13% high risk). It was significantly higher at site A (28% vs
      17%; p = 0.004) where patients were also significantly more likely to reside in
      areas of more deprivation than those at site B (IMD rank: 15,510 SD 8137 vs
      22,877 SD 6827; p < 0.001). COPD disease-severity was positively associated with
      malnutrition (p < 0.001) whilst a higher rank IMD was negatively associated with
      malnutrition (p = 0.014). CONCLUSIONS: Deprivation is a significant independent
      risk factor for malnutrition in outpatients with COPD. Consideration of
      deprivation is important in the identification of malnutrition and the
      nutritional management of patients with COPD.

PMID- 27866759
TI  - Adherence to healthy lifestyle factors and risk of death in men with diabetes
      mellitus: The Physicians' Health Study.
AB  - BACKGROUND & AIMS: The relationship between healthy lifestyle factors and
      mortality in people with type 2 diabetes is unclear. The purpose of this study
      was to examine whether healthy lifestyle factors are associated with mortality in
      people with type 2 diabetes. METHODS: We prospectively studied 1163 men with type
      2 diabetes from the Physicians' Health Study. Lifestyle factors consisted of
      currently not smoking, moderate drinking (1-2 drinks/day), vigorous exercise
      (1+/week), BMI < 25 kg/m2, and being in the top 2 quintiles of the alternate
      healthy eating index-2010 (AHEI-2010). Multivariate Cox regression models were
      used to estimate hazard ratios (95% confidence intervals) of mortality. RESULTS:
      At baseline, average age was 69 years and mean follow up was 9 years. About 22%
      of study participants had <=1 healthy lifestyle factor, 37% had two, 29% had
      three, and 12% had four or more healthy lifestyle factors. An inverse
      relationship was found between the number of lifestyle factors and total
      mortality. Compared with participants who had <=1 healthy lifestyle factor, the
      risk of death was 42% (95% CI; 19%-58%) lower for those with two healthy
      lifestyle factors, 41% (95% CI; 18%-58%) lower for those with three, and 44% (95%
      CI; 12%-64%) lower for those with 4 or more healthy lifestyle factors.
      CONCLUSION: Adherence to modifiable healthy lifestyle factors is associated with
      a lower risk of death among adult men with type 2 diabetes. Our study emphasizes
      the importance of educating individuals with diabetes to adhere to healthy
      lifestyle factors.

PMID- 27866760
TI  - Polyurethane foam impregnated with lignin as a filler for the removal of crude
      oil from contaminated water.
AB  - The present study describes the influence of the concentration of lignin when
      used as a filler in polyurethane foam for crude oil sorption. The foams (lignin 0
      20wt%) were characterized by Fourier transform infrared spectroscopy (FTIR),
      scanning electron microscopy (SEM), thermogravimetric analysis, contact angle and
      density. The FTIR analysis confirmed urethane linkage formation, showing that the
      chemical structure of the polymer was preserved, despite the addition of
      different lignin concentrations. Thermogravimetric analysis showed that the
      presence of lignin has altered the onset temperature (Tonset) of the foams,
      decreasing as the concentration of lignin is increased. The contact angle
      analysis showed a decrease in the hydrophobicity of the foams with increasing
      lignin concentration. All modified foams showed an improvement in the oil
      sorption capacity in a PUF/oil/water system, and the PUF-10 showed an improvement
      of about 35.5% compared to the PUF-blank. The Langmuir isotherm showed a better
      fit to the data and predicted a maximum oil adsorption of 28.9gg-1 by the PUF-10.
      The DeltaG degrees  value of -4.4kJmol-1 indicated that crude oil adsorption
      process by PUF-10 was spontaneous. The results of reuse of the PUF-10 showed that
      oil removal efficiency remained greater than 95% after five consecutive cycles.

PMID- 27866761
TI  - Degradation of sulfamethazine using Fe3O4-Mn3O4/reduced graphene oxide hybrid as
      Fenton-like catalyst.
AB  - In this paper, Fe3O4-Mn3O4/reduced graphene oxide (RGO) hybrid was synthesized
      through polyol process and impregnation method and used as heterogeneous Fenton
      like catalyst for degradation of sulfamethazine (SMT) in aqueous solution. The
      hybrid catalyst had higher catalytic efficiency compared with Fe3O4-Mn3O4 and
      Mn3O4 as catalyst for degradation of SMT. The effects of pH value, H2O2
      concentration, catalyst dosage, initial SMT concentration and temperature on SMT
      degradation were investigated. The removal efficiency of SMT was about 98% at
      following optimal conditions: pH=3, T=35 degrees C, Fe3O4/Mn3O4-RGO
      composites=0.5g/L, H2O2=6mM. The inhibitor experiments indicated that the main
      active species was hydroxyl radicals (.OH) on catalyst surface. At last, the
      possible catalytic mechanism was proposed.

PMID- 27866762
TI  - Synthesis and characterization of polyacrylic acid- grafted-carboxylic
      graphene/titanium nanotube composite for the effective removal of enrofloxacin
      from aqueous solutions: Adsorption and photocatalytic degradation studies.
AB  - Polyacrylic acid-grafted-carboxylic graphene/titanium nanotube (PAA-g-CGR/TNT)
      composite was synthesized. It was effectively used as adsorbent as well as
      photocatalyst. The composite was characterized by FTIR, XRD, SEM, TEM, Surface
      Area Analyzer, XPS and DRS. The photocatalytic activity of PAA-g-CGR/TNT
      composite was evaluated on the basis of the degradation of pollutants by using
      sunlight. The band gap of the prepared photocatalyst was found to be 2.6eV. The
      removal of the antibiotic enrofloxacin (ENR) was achieved by two step mechanism
      based on adsorption and photodegradation. The maximum adsorption was observed at
      pH 5.0. The best fitted kinetic model was found to be pseudo-second-order. The
      maximum adsorption was observed at 30 degrees C. The maximum adsorption capacity
      was found to be 13.40mg/g. The kinetics of photodegradation of ENR onto PAA-g
      CGR/TNT composite follow first-order kinetics and optimum pH was found to be 5.0.
      The regeneration and reuse of the adsorbent-cum-photocatalyst were also examined
      upto five cycles.

PMID- 27866764
TI  - Thermodynamic features of dioxins' adsorption.
AB  - In this paper, the six more poisonous species among all congeners of dioxin group
      are taken into account, and the P-T diagram for each of them is developed.
      Starting from the knowledge of vapour tensions and thermodynamic parameters, the
      theoretical adsorption isotherms are calculated according to the Langmuir's
      model. In particular, the Langmuir isotherm parameters (K and wmax) have been
      validated through the estimation of the adsorption heat (DeltaHads), which varies
      in the range 20-24kJ/mol, in agreement with literature values. This result will
      allow to put the thermodynamical basis for a rational design of different process
      units devoted to dioxins removal.

PMID- 27866763
TI  - Direct and indirect photodegradation pathways of cytostatic drugs under UV
      germicidal irradiation: Process kinetics and influences of water matrix species
      and oxidant dosing.
AB  - The ever-increasing consumption of various cytostatic drugs (CSDs) has attracted
      growing public concern in recent years. The photodegradation of 8 CSDs was
      investigated using a low-pressure UV-254Hg lamp, resulting in fluence-based first
      order kinetic rate constants in the range of (0.20-6.97)*10-4cm2mJ-1. The
      influence of water matrix components, including natural dissolved organic matter
      (DOM), bicarbonate (HCO3-), nitrate (NO3-), chloride (Cl-), and sulfate (SO42-),
      was investigated. The degradation rates of CSDs decrease in the presence of DOM
      due to the competition for the UV light, but increase with addition of NO3- due
      to an indirect production of HO. Further investigation was carried out to
      evaluate the viability of UV treatment performances using two real water samples,
      namely treated water from a water treatment plant and secondary effluent from a
      wastewater treatment plant. The primary photodegradation byproducts of CSDs were
      identified using LC/MS/MS to investigate the mechanism of direct UV photolysis
      and indirect NO3--induced and DOM-induced photolysis. The degradation rates of
      CSDs increase significantly with the addition of H2O2 or S2O82- under UV
      irradiation, due to the generation of non-selective HO or selective SO4-. As an
      electrophilic radical, SO4- mainly reacts via electron transfer and selectively
      attacks certain electron-donating functional groups of CSDs.

PMID- 27866766
TI  - Age-specific effectiveness following each dose of acellular pertussis vaccine
      among infants and children in New Zealand.
AB  - BACKGROUND: Though it is believed the switch from whole cell to acellular
      pertussis vaccine has contributed to the resurgence of pertussis disease, few
      studies have evaluated vaccine effectiveness (VE) and duration of protection
      provided by an acellular vaccine schedule including three primary doses but no
      toddler-age dose. We assessed this schedule in New Zealand (NZ), a setting with
      historically high rates of pertussis disease, and low but recently improved
      immunisation coverage. We further evaluated protection following the preschool
      age booster dose. METHODS: We performed a nested case-control study using
      national-level healthcare data. Hospitalised and non-hospitalised pertussis was
      detected among children 6weeks to 7years of age between January 2006 and December
      2013. The NZ National Immunisation Register provided vaccination status for cases
      and controls. Conditional logistic regression was used to calculate dose-specific
      VE with duration of immunity examined by stratifying VE into ages aligned with
      the immunisation schedule. RESULTS: VE against pertussis hospitalisation was 93%
      (95% confidence interval [CI]: 87, 96) following three doses among infants aged 5
      11months who received three compared to zero doses. This protection was sustained
      through children's fourth birthdays (VE?91%). VE against non-hospitalised
      pertussis was also sustained after three doses, from 86% (95% CI: 80, 90) among 5
      11month olds to 84% (95% CI: 80, 88) among 3-year-olds. Following the first
      booster dose at 4years of age, the protective VE of 93% (95% CI: 90, 95) among 4
      year-olds continued through 7years of age (VE?91%). CONCLUSIONS: We found a high
      level of protection with no reduction in VE following both the primary course and
      the first booster dose. These findings support a 3-dose primary course of
      acellular vaccine with no booster dose until 4years of age.

PMID- 27866765
TI  - Safety, tolerability, and immunogenicity of a single dose 4-antigen or 3-antigen
      Staphylococcus aureus vaccine in healthy older adults: Results of a randomised
      trial.
AB  - BACKGROUND: The decline in immune function with age is a challenge to vaccine
      development. Following an initial study in adults aged 18-64years, this study
      evaluated the safety and immunogenicity of Staphylococcus aureus (S. aureus) 4
      antigen (SA4Ag) and 3-antigen (SA3Ag) vaccine in older adults. SA3Ag included
      capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to the
      nontoxic mutant form of diphtheria toxin (CRM197) and a recombinant version of
      clumping factor A (ClfA). SA4Ag included these antigens, with the addition of a
      recombinant manganese transporter C (rP305A or MntC). Both vaccines were
      unadjuvanted. METHODS: In this double-blind, sponsor-unblinded, placebo
      controlled, phase 1/2 study, 284 healthy adults (aged 65-85years) were randomised
      to receive a single dose of one of three formulations of SA4Ag with escalating
      dose levels of rP305A, SA3Ag, or placebo. Functional immune responses were
      measured using opsonophagocytic activity (OPA) killing and fibrinogen-binding
      inhibition (FBI) assays; immunogenicity was also assessed using a competitive
      Luminex(r) immunoassay (cLIA). T-cell responses were measured in a small subgroup
      of subjects using intracellular cytokine staining (ICS) assays. RESULTS: The
      results demonstrated rapid and robust functional immune responses to all antigens
      in healthy older adults. A high proportion of active vaccine recipients met the
      pre-defined antibody thresholds for each antigen at Day 29. SA4Ag elicited a dose
      level response to rP305A with up to a 13-fold rise in cLIA titres at Day 29.
      Opsonophagocytic activity (OPA) assays showed >50- and >20-fold rises in
      functional titres using S. aureus strains expressing CP5 and CP8, respectively,
      at Day 29. T-cell cytokine responses were not substantially above background
      levels. There were no safety concerns in this study population and no increases
      in adverse events with higher rP305A dose levels. CONCLUSIONS: Single-dose
      vaccination of SA4Ag and SA3Ag in healthy adults aged 65-85years safely induced
      rapid and robust functional immune responses, supporting further development of
      SA4Ag for the prevention of S. aureus disease in adults up to age 85years. TRIAL
      REGISTRATION NUMBER: NCT01643941.

PMID- 27866767
TI  - Minimization of hepatitis B infection among children in Jiangsu, China, 12years
      after integration of hepatitis B vaccine into the expanded program on
      immunization.
AB  - BACKGROUND: China has integrated hepatitis B vaccine into the Expanded Program on
      Immunization since 2002. We aimed to survey the seroprevalence of and immunity to
      hepatitis B virus (HBV) in children born from 2002 to 2014 in Jiangsu, China.
      METHODS: Totally 3442 children (M:F=2072:1370) at the age of 7months to 12years
      (5.5+/-3.6), from five cities and rural areas across Jiangsu province, were
      enrolled. Blood samples were measured for HBV markers by ELISA and quantitative
      microparticle enzyme immunoassay. HBV DNA was tested by real-time PCR and S
      region was amplified by nested PCR. RESULTS: Twelve (0.35%) children were
      positive for hepatitis B surface antigen (HBsAg) and 34 (0.99%) were HBsAg
      negative and positive for antibody against hepatitis B core antigen (anti-HBc).
      Totally 2542 (73.85%) children had anti-HBs levels ?10mIU/ml and 535 (15.54%)
      with 2-9.9mIU/ml. All 12 HBsAg-positive children had detectable HBV DNA with a
      mean level of 6.1+/-1.7logIU/ml (3.3-8.1logIU/ml); 8 were genotype C and 4 were
      genotype B. No mutation was detected in the a determinant of HBsAg. HBV DNA was
      not detected in all the 34 children with positive anti-HBc and negative HBsAg.
      CONCLUSION: HBsAg prevalence among children in Jiangsu born after the
      introduction of universal vaccination against hepatitis B has significantly
      decreased. No mutation of S gene is associated with vaccine failure in the cohort
      of children.

PMID- 27866768
TI  - Estimating the burden of rubella virus infection and congenital rubella syndrome
      through a rubella immunity assessment among pregnant women in the Democratic
      Republic of the Congo: Potential impact on vaccination policy.
AB  - BACKGROUND: Rubella-containing vaccines (RCV) are not yet part of the Democratic
      Republic of the Congo's (DRC) vaccination program; however RCV introduction is
      planned before 2020. Because documentation of DRC's historical burden of rubella
      virus infection and congenital rubella syndrome (CRS) has been minimal, estimates
      of the burden of rubella virus infection and of CRS would help inform the
      country's strategy for RCV introduction. METHODS: A rubella antibody
      seroprevalence assessment was conducted using serum collected during 2008-2009
      from 1605 pregnant women aged 15-46years attending 7 antenatal care sites in 3 of
      DRC's provinces. Estimates of age- and site-specific rubella antibody
      seroprevalence, population, and fertility rates were used in catalytic models to
      estimate the incidence of CRS per 100,000 live births and the number of CRS cases
      born in 2013 in DRC. RESULTS: Overall 84% (95% CI 82, 86) of the women tested
      were estimated to be rubella antibody seropositive. The association between age
      and estimated antibody seroprevalence, adjusting for study site, was not
      significant (p=0.10). Differences in overall estimated seroprevalence by study
      site were observed indicating variation by geographical area (p?0.03 for all).
      Estimated seroprevalence was similar for women declaring residence in urban (84%)
      versus rural (83%) settings (p=0.67). In 2013 for DRC nationally, the estimated
      incidence of CRS was 69/100,000 live births (95% CI 0, 186), corresponding to
      2886 infants (95% CI 342, 6395) born with CRS. CONCLUSIONS: In the 3 provinces,
      rubella virus transmission is endemic, and most viral exposure and seroconversion
      occurs before age 15years. However, approximately 10-20% of the women were
      susceptible to rubella virus infection and thus at risk for having an infant with
      CRS. This analysis can guide plans for introduction of RCV in DRC. Per World
      Health Organization recommendations, introduction of RCV should be accompanied by
      a campaign targeting all children 9months to 14years of age as well as
      vaccination of women of child bearing age through routine services.

PMID- 27866769
TI  - Modular virus-like particles for sublingual vaccination against group A
      streptococcus.
AB  - Infection with Group A streptococcus (GAS)-an oropharyngeal pathogen-leads to
      mortality and morbidity, primarily among developing countries and indigenous
      populations in developed countries. The development of safe and affordable GAS
      vaccines is challenging, due to the presence of various unique GAS serotypes,
      antigenic variation within the same serotype, and potential auto-immune
      responses. In the present study, we evaluated the use of a sublingual freeze
      dried (FD) formulation based on immunogenic modular virus-like particles (VLPs)
      carrying the J8 peptide (J8-VLPs) as a potential safe and cost-effective GAS
      vaccine for inducing protective systemic and mucosal immunity. By using in vivo
      tracing of the sublingual J8-VLPs, we visualized the draining of J8-VLPs into the
      submandibular lymph nodes, in parallel with its rapid absorption into the
      systemic circulation, which support the induction of effective immune responses
      in both systemic and mucosal compartments. The sublingual administration of J8
      VLPs resulted in a high serum IgG antibody level, with a good balance of Th1 and
      Th2 immune responses. Of note, sublingual vaccination with J8-VLPs elicited high
      levels of IgA antibody in the saliva. The co-administration of mucosal adjuvant
      cholera toxin (CT) further enhanced the increase in salivary IgA antibody levels
      induced by the J8-VLPs formulation. Moreover, the levels of salivary IgA and
      serum IgG observed following the administration of the CT-adjuvanted FD
      formulation of J8-VLPs (FD-J8-VLPs) and non-FD formulation of J8-VLPs were
      comparable. In fact, the saliva isolated from mice immunized with J8-VLPs and FD
      J8-VLPs with CT demonstrated opsonizing activity against GAS in vitro. Thus, we
      observed that the sublingually delivered FD formulation of microbially produced
      modular VLPs could prevent and control GAS diseases in endemic areas in a cost
      effective manner.

PMID- 27866771
TI  - The changing face of vaccines and vaccination.

PMID- 27866770
TI  - Tetanus vaccination is associated with differential DNA-methylation: Reduces the
      risk of asthma in adolescence.
AB  - BACKGROUND: Vaccinations have been suggested to be associated with increased risk
      of allergic diseases. Tetanus vaccination is one of the most frequently
      administered vaccines as a part of wound management and was also found to be
      associated with increased serum IgE levels. We hypothesized that the vaccination
      modifies the risk of allergic diseases through epigenetic changes such as DNA
      methylation. METHOD: Data on tetanus vaccination between 10 and 18years of age
      was collected from a birth cohort established on the Isle of Wight UK in 1989.
      DNA methylation data were collected from individuals at different ages (at birth
      [n=30], age 10 [n=34], age 18 [n=245] and during pregnancy [n=121]) using the
      Illumina Infinium HumanMethylation450K array. Firstly, we performed an epigenome
      wide screening to identify cytosine-phosphate-guanine sites (CpGs) associated
      with tetanus vaccination in 18-year-olds. Secondly, we tested their association
      with asthma, allergic sensitization, eczema, serum IgE and pulmonary lung
      function (FVC, FEV1, FEV1/FVC, and FEF25-75%). We then described changes in the
      methylation of the selected CpG sites over age, and by vaccination status.
      RESULTS: Tetanus vaccination was found to be associated with decreased
      methylation of cg14472551 (p value 0.5*10-5, FDR-adjusted p value 2.1*10-4) and
      increased methylation of cg01669161 (p value 0.0007, FDR-adjusted p value 0.014).
      Both CpGs, in turn, were associated with decreased risk of asthma at 18years of
      age. Cg14472551 is located in an intron of KIAA1549L, whose protein binds to a B
      cell commitment transcription factor; cg01669161 is located between an antisense
      regulator of the proteasome assembly chaperone PSMG3, and TFAMP1, a pseudogene.
      Increased methylation of cg01669161 was also associated with decreased serum IgE
      levels. CONCLUSION: DNA methylation changes following tetanus vaccination may
      offer a novel prospect to explain a differential occurrence of asthma in
      adolescence.

PMID- 27866773
TI  - Influenza H7N9 LAH-HBc virus-like particle vaccine with adjuvant protects mice
      against homologous and heterologous influenza viruses.
AB  - The long alpha-helix (LAH) region located in influenza virus hemagglutinin (HA)
      shows conservation among different influenza A strains, which could be used as a
      candidate target of influenza vaccines. Moreover, the hepatitis B virus core
      protein (HBc) is a carrier for heterologous epitopes in eliciting effective
      immune responses. We inserted the LAH region of H7N9 influenza virus into the HBc
      and prepared the LAH-HBc protein, which were capable of self-assembly into virus
      like particles (VLP), by using E. coli expression system. Intranasal immunization
      of the LAH-HBc VLP in combination with chitosan adjuvant or CTB* adjuvant in mice
      could induce both humoral and cellular immune responses effectively and provide
      complete protection against lethal challenge of homologous H7N9 virus or
      heterologous H3N2 virus, as well as partial protection against lethal challenge
      of heterologous H1N1 virus. These results provide a proof of concept for LAH-HBc
      VLP vaccine that would be fast and easy to be produced and might be an ideal
      candidate as a rapid-response tool against a future influenza pandemic.

PMID- 27866774
TI  - Complement-independent dengue virus type 1 infection-enhancing antibody reduces
      complement-dependent and -independent neutralizing antibody activity.
AB  - Dengue fever and dengue hemorrhagic fever are globally important mosquito
      transmitted viral diseases. However, the only licensed vaccine is not highly
      protective. Viremia is related to disease severity in infected humans, and it is
      thought to be reduced by neutralizing antibodies but increased by infection
      enhancing antibodies. We established an assay system to measure the balance
      between neutralizing and enhancing antibodies and found that most dengue-immune
      individuals in endemic areas carry complement-independent enhancing antibodies
      (CiEAb). Studying CiEAb is important for dengue vaccine development because the
      enhancing activity of CiEAb does not decrease in the presence of complement,
      which can reduce the enhancing activity of other antibodies in vitro. Here, we
      investigated the effects of CiEAb on the activity of neutralizing antibodies
      (mainly, complement-dependent neutralizing antibodies; CdNAb) using cocktails of
      mouse monoclonal antibodies (MAbs) against dengue virus type 1 (DENV-1). These
      cocktails included MAbs with enhancing activity only (represented by D1-V-3H12
      [3H12]) or neutralizing activity only (represented by D1-IV-7F4 [7F4]). Because
      3H12, an IgG1 subclass antibody, is complement-independent and cross-reacted with
      all dengue serotypes, it is a suitable model of CiEAb. An approximately equal
      amount of 3H12 abolished the neutralizing activity of 7F4. The complement
      dependent neutralizing activities of the IgG2a and IgG2b variants of 7F4 were
      also completely inhibited by ?3-fold concentrations of the IgG1 variant. The
      complement-dependent antibody activities of other anti-DENV-1 MAbs and those of
      MAbs directed against other serotypes were inhibited 50% by 3H12 at various
      mixing ratios, ranging from one-hundredth to 10-fold. The complement-dependent
      neutralizing activities of dengue-immune mouse ascites fluids were also
      effectively inhibited by 3H12. This suggests that concomitantly induced CiEAb
      exerts an unwanted effect on the protective capacity of a vaccine. Thus, the
      effective inhibition of the neutralizing activity of CdNAb by CiEAb has
      implications for dengue pathogenesis and vaccine development.

PMID- 27866775
TI  - The case for verbal autopsy in health systems strengthening.

PMID- 27866772
TI  - H1:IC31 vaccination is safe and induces long-lived TNF-alpha+IL-2+CD4 T cell
      responses in M. tuberculosis infected and uninfected adolescents: A randomized
      trial.
AB  - BACKGROUND: Control of the tuberculosis epidemic requires a novel vaccine that is
      effective in preventing tuberculosis in adolescents, a key target population for
      vaccination against TB. METHODS: Healthy adolescents, stratified by M.
      tuberculosis-infection status, were enrolled into this observer-blinded phase II
      clinical trial of the protein-subunit vaccine candidate, H1:IC31, comprising a
      fusion protein (H1) of Ag85B and ESAT-6, formulated with the IC31 adjuvant. Local
      and systemic adverse events and induced T cell responses were measured after one
      or two administrations of either 15MUg or 50MUg of the H1 protein. RESULTS: Two
      hundred and forty participants were recruited and followed up for 224days. No
      notable safety events were observed regardless of H1 dose or vaccination
      schedule. H1:IC31 vaccination induced antigen-specific CD4 T cells, co-expressing
      IFN-gamma, TNF-alpha and/or IL-2. H1:IC31 vaccination of M.tb-uninfected
      individuals preferentially drove the emergence of Ag85B and ESAT-6 specific TNF
      alpha+IL-2+CD4 T cells, while H1:IC31 vaccination of M.tb-infected individuals
      resulted in the expansion of Ag85B-specific but not ESAT-6-specific TNF-alpha+IL
      2+CD4 T cells. CONCLUSIONS: H1:IC31 was safe and immunogenic in uninfected and
      M.tb-infected adolescents. Two administrations of the 15MUg H1:IC31 dose induced
      the greatest magnitude immune response, and was considered optimal (South African
      National Clinical Trials Register, DoH-27-0612-3947; Pan African Clinical Trial
      Registry, PACTR201403000464306).

PMID- 27866776
TI  - Activation of alpha7 nicotinic acetylcholine receptors facilitates long-term
      potentiation at the hippocampal-prefrontal cortex synapses in vivo.
AB  - Activation of alpha7 nAChRs has been shown to improve performance in a variety of
      nonclinical assays of cognitive function. The role of alpha7 nAChRs in cognitive
      processes is likely related to their role in modulating synaptic transmission and
      plasticity that have been reported in cell culture, brain slices, and intact
      animals. Here we report the effects of the alpha7 nAChR agonist FRM-17874 on
      synaptic plasticity within the hippocampal-medial prefrontal cortex pathway. Long
      term potentiation (LTP) was generated by tetanic stimulation of CA1/subiculum
      region in urethane anesthetized male rats. Compared to saline controls, FRM-17874
      significantly increased LTP (F(3,16)=10.39, p=0.0005) at doses of 0.3 and
      1.0mg/kg but not with 3.0mg/kg, injected subcutaneously. Considering the
      physiological role of hippocampal LTP in mnemonic functions and memory formation,
      and the role of the hippocampal - prefrontal cortex pathway in working memory,
      the described neurophysiological effects could be a contributing mechanism
      underlying the cognitive effects of alpha7 nAChRs activation.

PMID- 27866779
TI  - Use of allogeneic tissue to treat infective valvular disease: Has everything been
      said?

PMID- 27866778
TI  - Historical Perspectives of The American Association for Thoracic Surgery: Aldo
      Castaneda.

PMID- 27866780
TI  - More than vital: Who bears the burden?

PMID- 27866782
TI  - No longer novel: The association of a dilated coronary sinus with left
      ventricular inflow obstruction.

PMID- 27866781
TI  - Endovascular repair of thoracoabdominal aortic aneurysms using fenestrated and
      branched endografts.
AB  - PURPOSE: The study purpose was to review the outcomes of patients treated for
      thoracoabdominal aortic aneurysms using endovascular repair with fenestrated and
      branched stent-grafts in a single center. METHODS: We reviewed the clinical data
      of the first 185 consecutive patients (134 male; mean age, 75 +/- 7 years)
      treated for thoracoabdominal aortic aneurysms using fenestrated and branched
      stent-grafts. Graft design evolved from physician-modified endografts (2007-2013)
      to off-the-shelf or patient-specific manufactured devices in patients enrolled in
      a prospective physician-sponsored investigational device exemption protocol (NCT
      1937949 and 2089607). Outcomes were reported for extent IV and extent I to III
      thoracoabdominal aortic aneurysms, including 30-day mortality, major adverse
      events, patient survival, primary target vessel patency, and reintervention.
      RESULTS: A total of 112 patients (60%) were treated for extent IV
      thoracoabdominal aortic aneurysms, and 73 patients (40%) were treated for extent
      I to III thoracoabdominal aortic aneurysms. Demographics and cardiovascular risk
      factors were similar in both groups. A total of 687 renal-mesenteric arteries
      (3.7 vessels/patient) were targeted by 540 fenestrations and 147 directional
      branches. Technical success was 94%. Thirty-day mortality was 4.3%, including a
      mortality of 1.8% for extent IV and 8.2% for extent I to III thoracoabdominal
      aortic aneurysms (P = .03). Mortality decreased in the second half of clinical
      experience from 7.5% to 1.2%, including a decrease of 3.3% to 0% for extent IV
      thoracoabdominal aortic aneurysms (P = .12) and 15.6% to 2.4% for extent I to III
      thoracoabdominal aortic aneurysms (P = .04). Early major adverse events occurred
      in 36 patients (32%) with extent IV thoracoabdominal aortic aneurysms and 26
      patients (36%) with extent I to III thoracoabdominal aortic aneurysms, including
      spinal cord injury in 2 patients (1.8%) and 4 patients (3.2%), respectively. Mean
      follow-up was 21 +/- 20 months. At 5 years, patient survival (56% and 59%, P =
      .37) and freedom from any reintervention (50% and 53%, P = .26) were similar in
      those with extent IV and extent I to III thoracoabdominal aortic aneurysms.
      Primary patency was 93% at 5 years. CONCLUSIONS: Endovascular repair of
      thoracoabdominal aortic aneurysms can be performed with high technical success
      and low mortality and morbidity. However, the need for secondary reinterventions
      and continued graft surveillance represents major limitations compared with
      results of conventional open surgical repair. Long-term follow-up is needed
      before the widespread use of these techniques in younger or lower-risk patients.

PMID- 27866784
TI  - Endothelial dysfunction or anything else?

PMID- 27866783
TI  - Characterizing cardiac arrest in children undergoing cardiac surgery: A single
      center study.
AB  - OBJECTIVES: To characterize cardiac arrest in children undergoing cardiac surgery
      using single-center data from the Society of Thoracic Surgeons and Pediatric
      Advanced Life Support Utstein-Style Guidelines. METHODS: Patients aged 18 years
      or less having a cardiac arrest for 1 minute or more during the same hospital
      stay as heart operation qualified for inclusion (2002-2014). Patients having a
      cardiac arrest both before or after heart operation were included. Heart
      operations were classified on the basis of the first cardiovascular operation of
      each hospital admission (the index operation). The primary outcome was survival
      to hospital discharge. RESULTS: A total of 3437 children undergoing at least 1
      heart operation were included. Overall rate of cardiac arrest among these
      patients was 4.5% (n = 154) with survival to hospital discharge of 84 patients
      (66.6%). Presurgery cardiac arrest was noted among 28 patients, with survival of
      21 patients (75%). Among the 126 patients with postsurgery cardiac arrest,
      survival was noted among 84 patients (66.6%). Regardless of surgical case
      complexity, the median days between heart operation and cardiac arrest, duration
      of cardiac arrest, and survival after cardiac arrest were similar. The
      independent risk factors associated with improved chances of survival included
      shorter duration of cardiac arrest (odds ratio, 1.12; 95% confidence interval,
      1.05-1.20; P = .01) and use of defibrillator (odds ratio, 4.51; 95% confidence
      interval, 1.08-18.87; P = .03). CONCLUSIONS: This single-center study
      demonstrates that characterizing cardiac arrest in children undergoing cardiac
      surgery using definitions from 2 societies helps to increase data granularity and
      understand the relationship between cardiac arrest and heart operation in a
      better way.

PMID- 27866785
TI  - Cardiac cellular reprogramming with transient expression vectors: Less is more.

PMID- 27866786
TI  - Why compromise with an elderly patient?

PMID- 27866787
TI  - Cavopulmonary assist: Bridge to Fontan repair of single-ventricle circulation.

PMID- 27866788
TI  - String no ring.

PMID- 27866789
TI  - First case of a sutureless Perceval valve delayed proximal migration.

PMID- 27866790
TI  - Mitral repair in children with connective tissue disorders: On the edge, over the
      edge, or edge-to-edge?

PMID- 27866791
TI  - Mesenchymal stem cells: The roles and functions in cutaneous wound healing and
      tumor growth.
AB  - Mesenchymal stem cells (MSCs) are bone marrow-derived non-hematopoietic
      progenitor cells. MSCs are able to differentiate into various types of cells,
      including chondrocytes, adipocytes, osteocytes, myocytes, endothelial cells, and
      keratinocytes. There is increasing evidence that MSCs might be located external
      to the vasculature, and that perivascular cells in the skin, generally called as
      "pericytes", might include MSCs. It has been suggested that MSCs localized around
      blood vessels might migrate into wounds and contribute to the restoration of
      injured tissues. Many studies have demonstrated that intravenous or intradermal
      administration of MSCs enhanced cutaneous wound healing, such as acute incisional
      and excisional wounds, diabetic ulcers, radiation ulcers, and burns in animals
      and humans. Several mechanisms of the acceleration of wound healing by MSCs have
      been identified, including the enhancement of angiogenesis by secretion of pro
      angiogenic factors and the differentiation into endothelial cells and/or
      pericytes, M2 macrophages polarization, the recruitment of endogenous
      stem/progenitor cells, extracellular matrix production and remodeling, and
      immunosuppressive effects. Since the microenvironments of wounds and/or injured
      tissues are similar to those of tumors, MSCs also play similar roles in malignant
      tumors, such as the enhancement of angiogenesis, M2 macrophages polarization, and
      immunosuppressive effects. In addition, the mechanisms of homing of MSCs might
      have a commonality in the pathogenesis of wound healing and tumors. Thus, the
      regulating factors of MSCs, including MFG-E8, could be a therapeutic target and
      lead to the establishment of new therapeutic approaches for both intractable
      wound healing and tumors.

PMID- 27866792
TI  - 210Po secretion from sweat glands.
AB  - The results of the research indicated that the 210Po activity concentration in
      sweat samples was between 0.22 +/- 0.03 to 2.10 +/- 0.15 mBq.g-1 d.w. The
      obtained results of the studies showed that smoking and eating fish led to higher
      activity concentrations of 210Po in sweat in comparison to the control group.
      Statistical analysis of 210Po activity concentrations in sweat samples showed
      significant differences between control, smoking, fish eating and age groups,
      while no significant differences was found for 210Po between volunteers as far as
      gender is concerned.

PMID- 27866794
TI  - Treatment of Symptomatic Acromioclavicular Joint Instability by a Docking
      Technique: Clinical Indications, Surgical Technique, and Outcomes.
AB  - PURPOSE: To report functional and objective outcomes resulting from surgical
      treatment of patients with symptomatic type III through V acromioclavicular (AC)
      joint injury by use of a modification of the anatomic AC joint reconstruction
      developed by Carofino and Mazzocca. METHODS: The study included all patients
      treated in 2009-2014 who presented with a history of direct trauma to the
      shoulder; deformity of the AC joint on clinical examination; radiographic
      findings that would classify the injury as a Rockwood type III, IV, or V injury;
      AC joint instability on clinical examination; and self-reported deficits of arm
      function on initial presentation, in whom a comprehensive and directed
      nonoperative program failed. The surgical procedure used an allograft with
      reinforcing internal sutures passed around the coracoid and through anatomically
      positioned clavicular holes for the coracoclavicular (CC) ligaments, used a
      docking technique for reconstruction of the superior AC ligaments, and included
      repair of the native AC ligaments. Outcomes were reported for patients with a
      minimum follow-up period of 1.5 years. Outcome measurements included dynamic
      static stability evaluation and Disabilities of the Arm, Shoulder and Hand (DASH)
      scores. RESULTS: The study included 15 patients with 15 affected shoulders. The
      postsurgical follow-up period averaged 3 years (range, 1.5-5 years).
      Postoperatively, one patient showed loss of reduction after a fall. All others
      showed 2-dimensional radiographic stability and 3-dimensional dynamic clinical
      stability. Static radiographic measurement of the CC distance at discharge
      averaged 0.93 cm compared with 2.7 cm on initial examination (P < .0001). Patient
      reported outcomes at an average of 3 years' follow-up showed a DASH score of 13
      compared with a preoperative DASH score of 51 (P < .0001). CONCLUSIONS: This
      study confirms that anatomic CC ligament reconstruction and repair or
      reconstruction of the AC ligaments help restore arm function as shown by the
      patient-specific and clinical outcome metrics. These results were achieved by
      correction of the deformity, which in turn allowed for the obtainment of static
      and dynamic stability. LEVEL OF EVIDENCE: Level IV.

PMID- 27866793
TI  - Tracking the dissemination of a culturally targeted brochure to promote awareness
      of hereditary breast and ovarian cancer among Black women.
AB  - OBJECTIVE: Black women have a higher rate of BRCA1 and BRCA2 (BRCA) mutations,
      compared with other populations, that increases their risk for hereditary breast
      and ovarian cancer (HBOC). However, Black women are less likely to know about
      HBOC and genetic testing. Based on a request from a community advisory panel of
      breast cancer survivors, community leaders and healthcare providers in the Black
      community, our team developed a culturally targeted educational brochure to
      promote awareness of HBOC among Black women. METHODS: To reach the target
      population we utilized a passive dissemination strategy. Using Diffusion of
      Innovations (DOI) as a framework, we traced dissemination of the brochure over a
      five year period using self-addressed postcards contained inside the brochure
      that included several open-ended questions about the utility of the brochure, and
      a field for written comments. Closed-ended responses were analyzed using
      descriptive statistics and thematic analysis was conducted on the open-ended
      responses. RESULTS: DOI captured the proliferation of the brochure among Black
      women across the US. PRACTICE IMPLICATIONS: The use of passive dissemination
      strategies among pre-existing social networks proved to be a useful and
      sustainable method for increasing knowledge of HBOC among Black women.

PMID- 27866795
TI  - Midterm Outcomes After Arthroscopic Anteroinferior Capsular Release for the
      Treatment of Idiophatic Adhesive Capsulitis.
AB  - PURPOSE: The purpose of this study is to report the early and midterm functional
      outcomes and complications of a consecutive series of patients with primary
      adhesive capsulitis who were treated with isolated anteroinferior arthroscopic
      capsular release after they did not respond to conservative treatment. METHODS:
      Thirty-two consecutive patients with idiopathic adhesive capsulitis who did not
      respond to conservative physiotherapy were included in the study. Arthroscopic
      anteroinferior capsular release was performed in all cases. The primary outcome
      was improvement in range of motion in the short- and midterm follow-up. We also
      evaluated pain relief with the visual analog scale, functional outcomes with the
      Constant-Murley score, and we registered postoperative complications. RESULTS:
      The mean age was 49.6 years (range, 33-68 years) and the mean follow-up was 63
      months (range, 18-84). Overall, there was significant improvement in the Constant
      Murley score from 42.4 to 86 points (P < .001). The visual analog scale decreased
      by approximately 6.3 points compared with the preoperative value (P < .001). All
      parameters improved significantly the first 6 months and then remained stable
      until the end of follow-up (P < .001). There was an additional minor improvement
      in both parameters between the sixth month and the final follow-up; however, this
      improvement was less than in the first 6 months and it was not statistically
      significant. CONCLUSIONS: In patients who don't respond to conservative treatment
      for primary adhesive capsulitis, isolated anteroinferior capsular release
      provides a reliable improvement in pain and range of motion that is maintained in
      the mid-term follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic, case series
      study.

PMID- 27866796
TI  - Interplay between Hippocampal Sharp-Wave-Ripple Events and Vicarious Trial and
      Error Behaviors in Decision Making.
AB  - Current theories posit that memories encoded during experiences are subsequently
      consolidated into longer-term storage. Hippocampal sharp-wave-ripple (SWR) events
      have been linked to this consolidation process during sleep, but SWRs also occur
      during awake immobility, where their role remains unclear. We report that awake
      SWR rates at the reward site are inversely related to the prevalence of vicarious
      trial and error (VTE) behaviors, thought to be involved in deliberation
      processes. SWR rates were diminished immediately after VTE behaviors and an
      increase in the rate of SWR events at the reward site predicted a decrease in
      subsequent VTE behaviors at the choice point. Furthermore, SWR disruptions
      increased VTE behaviors. These results suggest an inverse relationship between
      SWRs and VTE behaviors and suggest that awake SWRs and associated planning and
      memory consolidation mechanisms are engaged specifically in the context of higher
      levels of behavioral certainty.

PMID- 27866798
TI  - Long-Distance Descending Spinal Neurons Ensure Quadrupedal Locomotor Stability.
AB  - Locomotion is an essential animal behavior used for translocation. The spinal
      cord acts as key executing center, but how it coordinates many body parts located
      across distance remains poorly understood. Here we employed mouse genetic and
      viral approaches to reveal organizational principles of long-projecting spinal
      circuits and their role in quadrupedal locomotion. Using neurotransmitter
      identity, developmental origin, and projection patterns as criteria, we uncover
      that spinal segments controlling forelimbs and hindlimbs are bidirectionally
      connected by symmetrically organized direct synaptic pathways that encompass
      multiple genetically tractable neuronal subpopulations. We demonstrate that
      selective ablation of descending spinal neurons linking cervical to lumbar
      segments impairs coherent locomotion, by reducing postural stability and speed
      during exploratory locomotion, as well as perturbing interlimb coordination
      during reinforced high-speed stepping. Together, our results implicate a highly
      organized long-distance projection system of spinal origin in the control of
      postural body stabilization and reliability during quadrupedal locomotion.

PMID- 27866797
TI  - The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in
      Cortical Networks.
AB  - Models of cortical dynamics often assume a homogeneous connectivity structure.
      However, we show that heterogeneous input connectivity can prevent the dynamic
      balance between excitation and inhibition, a hallmark of cortical dynamics, and
      yield unrealistically sparse and temporally regular firing. Anatomically based
      estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical
      simulations of this circuit indicate that the local network possesses substantial
      heterogeneity in input connectivity, sufficient to disrupt excitation-inhibition
      balance. We show that homeostatic plasticity in inhibitory synapses can align the
      functional connectivity to compensate for structural heterogeneity.
      Alternatively, spike-frequency adaptation can give rise to a novel state in which
      local firing rates adjust dynamically so that adaptation currents and synaptic
      inputs are balanced. This theory is supported by simulations of L4 barrel cortex
      during spontaneous and stimulus-evoked conditions. Our study shows how synaptic
      and cellular mechanisms yield fluctuation-driven dynamics despite structural
      heterogeneity in cortical circuits.

PMID- 27866799
TI  - Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex
      Regulation and Interplay with Memory and Decision Processes.
AB  - We developed a circuit model of spiking neurons that includes multiple pathways
      in the basal ganglia (BG) and is endowed with feedback mechanisms at three
      levels: cortical microcircuit, corticothalamic loop, and cortico-BG
      thalamocortical system. We focused on executive control in a stop signal task,
      which is known to depend on BG across species. The model reproduces a range of
      experimental observations and shows that the newly discovered feedback projection
      from external globus pallidus to striatum is crucial for inhibitory control.
      Moreover, stopping process is enhanced by the cortico-subcortical reverberatory
      dynamics underlying persistent activity, establishing interdependence between
      working memory and inhibitory control. Surprisingly, the stop signal reaction
      time (SSRT) can be adjusted by weights of certain connections but is insensitive
      to other connections in this complex circuit, suggesting novel circuit-based
      intervention for inhibitory control deficits associated with mental illness. Our
      model provides a unified framework for inhibitory control, decision making, and
      working memory.

PMID- 27866801
TI  - Microalgal post-treatment of anaerobically digested agro-industrial wastes for
      nutrient removal and lipids production.
AB  - The aim of this study was to investigate the effectiveness of cultivating
      Parachlorella kessleri and Acutodesmus obliquus, in anaerobic digestion effluent
      (ADE) derived from the co-digestion of end-of-life dairy products with mixtures
      of agro-industrial wastes. To this end, their performance under sterile and non
      sterile conditions and different ADE loadings was evaluated, in terms of biomass
      and lipid production, nutrient removal efficiency and vitality of the
      photosynthetic apparatus. 10% (v/v) ADE loading inhibited growth over 9-12days of
      cultivation, however biomass yields of 1.1 and 1gL-1, 22.7% and 19.5% (w/w) fatty
      acids concentration, as well as NH3-N assimilation of 49.7mgL-1 and 32.3mgL-1 and
      TP removal of 84.2% and 84% were recorded for P. kessleri and A. obliquus,
      respectively. Among all the ADE-based treatments tested, P. kessleri outperformed
      A. obliquus, with no differences observed between sterilized and non-sterilized
      ADE.

PMID- 27866800
TI  - Neural Architecture of Hunger-Dependent Multisensory Decision Making in C.
      elegans.
AB  - Little is known about how animals integrate multiple sensory inputs in natural
      environments to balance avoidance of danger with approach to things of value.
      Furthermore, the mechanistic link between internal physiological state and threat
      reward decision making remains poorly understood. Here we confronted C. elegans
      worms with the decision whether to cross a hyperosmotic barrier presenting the
      threat of desiccation to reach a source of food odor. We identified a specific
      interneuron that controls this decision via top-down extrasynaptic aminergic
      potentiation of the primary osmosensory neurons to increase their sensitivity to
      the barrier. We also establish that food deprivation increases the worm's
      willingness to cross the dangerous barrier by suppressing this pathway. These
      studies reveal a potentially general neural circuit architecture for internal
      state control of threat-reward decision making.

PMID- 27866802
TI  - Effective degradation of aflatoxin B1 using a novel thermophilic microbial
      consortium TADC7.
AB  - We constructed a novel thermophilic microbial consortium, TADC7, with stable and
      efficient aflatoxin B1 (AFB1) degradation activity. The microbial consortium
      degraded more than 95% of the toxin within 72h when cultured with AFB1, and the
      optimum temperature was 55-60 degrees C. TADC7 tolerated high doses of AFB1, with
      no inhibitory effects up to 5000MUgL-1 AFB1; moreover, the degradation kinetics
      fit well with the Monod model. The proteins or enzymes in the TADC7 cell-free
      supernatant played a major role in AFB1 degradation. AFB1 degradation by the cell
      free supernatant was stable up to 90 degrees C, with an optimal pH of 8-10. We
      performed 16S rRNA sequencing to determine TADC7 community structure dynamics;
      the results indicated that Geobacillus and Tepidimicrobium played major roles in
      AFB1 degradation.

PMID- 27866803
TI  - Effect of hydrothermal pretreatment on Miscanthus anaerobic digestion.
AB  - Miscanthus is a promising source of bioenergy with high lignocellulose content.
      This paper studied the effect of hydrothermal pretreatment on Miscanthus biogas
      production. Different pretreatment temperature from 125 to 200 degrees C was
      tested. After pretreatment, hemicellulose was partially removed and this led to a
      change in cellulose accessibility. Enzymatic hydrolysis was used to examine the
      digestibility of different samples. There was no obvious enhancement in low
      temperature (125 and 150 degrees C) conditions. According to the results, 200
      degrees C hydrothermal pretreatment was the optimal condition saving 50% on the
      digestion time and increasing glucose production 13.2 times compared with the raw
      material. Although the cellulose crystallinity increased after the pretreatment,
      its effect on biogas production and enzymatic hydrolysis was limited.

PMID- 27866804
TI  - Evaluation of ultrasound assisted potassium permanganate pre-treatment of spent
      coffee waste.
AB  - In the present study, novel pre-treatment for spent coffee waste (SCW) has been
      proposed which utilises the superior oxidising capacity of alkaline KMnO4
      assisted by ultra-sonication. The pre-treatment was conducted for different
      exposure times (10, 20, 30 and 40min) using different concentrations of KMnO4 (1,
      2, 3, 4, 5%w/v) at room temperature with solid/liquid ratio of 1:10. Pretreating
      SCW with 4% KMnO4 and exposing it to ultrasound for 20min resulted in 98%
      cellulose recovery and a maximum lignin removal of 46%. 1.7 fold increase in
      reducing sugar yield was obtained after enzymatic hydrolysis of KMnO4 pretreated
      SCW as compared to raw. SEM, XRD and FTIR analysis of the pretreated SCW revealed
      the various effects of pretreatment. Thermal behaviour of the pretreated
      substrate against the native biomass was also studied using DSC. Ultrasound
      assisted potassium permanganate oxidation was found to be an effective
      pretreatment for SCW, and can be a used as a potential feedstock pretreatment
      strategy for bioethanol production.

PMID- 27866805
TI  - Detergent assisted ultrasonication aided in situ transesterification for
      biodiesel production from oleaginous yeast wet biomass.
AB  - In situ transesterification of oleaginous yeast wet biomass for fatty acid methyl
      esters (FAMEs) production using acid catalyst, methanol with or without N-Lauroyl
      sarcosine (N-LS) treatment was performed. The maximum FAMEs yield obtained with
      or without N-LS treatment in 24h reaction time was 96.1+/-1.9 and 71+/-1.4% w/w,
      respectively. The N-LS treatment of biomass followed by with or without
      ultrasonication revealed maximum FAMEs yield of 94.3+/-1.9% and 82.9+/-1.8% w/w
      using methanol to lipid molar ratio 360:1 and catalyst concentration 360mM (64MUL
      H2SO4/g lipid) within 5 and 25min reaction time, respectively. The FAMEs
      composition obtained in in situ transesterification was similar to that obtained
      with conventional two step lipid extraction and transesterification process.
      Biodiesel fuel properties (density, kinematic viscosity, cetane number and total
      glycerol) were in accordance with international standard (ASTM D6751), which
      suggests the suitability of biodiesel as a fuel.

PMID- 27866806
TI  - Enhanced nutrient removal and mechanisms study in benthic fauna added surface
      flow constructed wetlands: The role of Tubifex tubifex.
AB  - This study designed a combined benthic fauna-T. orientalis-substrate-microbes
      surface-flow constructed wetlands (SFCWs) through the addition of T. tubifex.
      Results showed that, the removal efficiencies of nitrogen and phosphorus in the
      tested SFCWs achieved 81.14+/-4.16% and 70.49+/-7.60%, which were 22.27% and
      27.35% higher than that without T. tubifex. Lower nitrate (2.11+/-0.79mg/L) and
      ammonium (0.75+/-0.64mg/L) were also observed in the tested SFCWs, which were
      3.46mg/L and 0.52mg/L lower than that without T. tubifex. Microbial study
      confirmed the increased denitrifiers with T. tubifex. The lower nitrogen in
      effluent was also attributed to higher contents of nitrogen storage in sediment
      and T. orientalis due to the bioturbation of T. tubifex. Furthermore, with T.
      tubifex, higher proportions of particulate (22.66+/-3.96%) and colloidal
      phosphorus (20.57+/-3.39%) observed promoted phosphorus settlement and further
      absorption by T. orientalis. The outcomes of this study provides an ecological
      and economical strategy for improving the performance of SFCWs.

PMID- 27866809
TI  - Corrigendum to "High abundance of circulating megakaryocytic cells in chronic
      myeloid leukemia in Indian patients. Revisiting George Minot to re-interpret
      megakaryocytic maturation" [Blood Cell Mol. Dis. 60 (2016) 28-32].

PMID- 27866807
TI  - Genome-wide analysis of the nucleus accumbens identifies DNA methylation signals
      differentiating low/binge from heavy alcohol drinking.
AB  - Alcohol-use disorders encompass a range of drinking levels and behaviors,
      including low, binge, and heavy drinking. In this regard, investigating the
      neural state of individuals who chronically self-administer lower doses of
      alcohol may provide insight into mechanisms that prevent the escalation of
      alcohol use. DNA methylation is one of the epigenetic mechanisms that stabilizes
      adaptations in gene expression and has been associated with alcohol use. Thus, we
      investigated DNA methylation, gene expression, and the predicted neural effects
      in the nucleus accumbens core (NAcc) of male rhesus macaques categorized as "low"
      or "binge" drinkers, compared to "alcohol-naive" and "heavy" drinkers based on
      drinking patterns during a 12-month alcohol self-administration protocol. Using
      genome-wide CpG-rich region enrichment and bisulfite sequencing, the methylation
      levels of 2.6 million CpGs were compared between alcohol-naive (AN), low/binge
      (L/BD), and heavy/very heavy (H/VHD) drinking subjects (n = 24). Through regional
      clustering analysis, we identified nine significant differential methylation
      regions (DMRs) that specifically distinguished ANs and L/BDs, and then compared
      those DMRs among H/VHDs. The DMRs mapped to genes encoding ion channels,
      receptors, cell adhesion molecules, and cAMP, NF-kappabeta and Wnt signaling
      pathway proteins. Two of the DMRs, linked to PDE10A and PKD2L2, were also
      differentially methylated in H/VHDs, suggesting an alcohol-dose independent
      effect. However, two other DMRs, linked to the CCBE1 and FZD5 genes, had L/BD
      methylation levels that significantly differed from both ANs and H/VHDs. The
      remaining five DMRs also differentiated L/BDs and ANs. However, H/VHDs
      methylation levels were not distinguishable from either of the two groups.
      Functional validation of two DMRs, linked to FZD5 and PDE10A, support their role
      in regulating gene expression and exon usage, respectively. In summary, the
      findings demonstrate that L/BD is associated with unique DNA methylation
      signatures in the primate NAcc, and that the methylation signatures identify
      synaptic genes that may play a role in preventing the escalation of alcohol use.

PMID- 27866808
TI  - Combined beta-glucosylceramide and ambroxol hydrochloride in patients with
      Gaucher related Parkinson disease: From clinical observations to drug
      development.
AB  - Both patients with non-neuronopathic Gaucher disease (GD) and heterozygous GBA
      mutation carrier are at increased risk for Parkinson disease (PD). The risk for
      PD in these groups does not linearly increase with glucosylceramide (GC)
      accumulation or with acid beta-glucocerebrosidase (GCase) activity. This
      observation, together with other clinical systemic observations raises the
      possibility that extra-cellular GC actually has beneficial, anti-inflammatory,
      properties. Based on this hypothesis, we suggest here that the administration of
      supplementary oral GC to GBA carriers at risk for PD may slow inflammatory-driven
      secondary neuronal death. Such a treatment may act synergistically in GBA
      carriers once given in combination with an agent that prevent the primary
      pathologic process that leads to cell death. Ambroxol hydrochloride, a
      pharmacological chaperone, which reduces endoplasmic reticulum (ER) stress
      induced by accumulation of mutant misfolded GCase could serve as such an agent.
      The efficacy of this combined therapy, derived from clinical observations, in
      vivo and in vitro studies, should be evaluated in clinical trials.

PMID- 27866810
TI  - Histological characterisation of visceral changes in a patient with type 2
      Gaucher disease treated with enzyme replacement therapy.
AB  - Gaucher disease is a lysosomal storage disease caused by deficiency of
      glucocerebrosidase and accumulation of glucocerebroside. Three major sub-types
      have been described, type 2 is an acute neurological form that exhibits serious
      general symptoms and poor prognosis, compared with the other types. This case was
      a girl diagnosed with type 2 Gaucher disease at 12months of age who presented
      with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly,
      trismus and an eye movement disorder. Enzyme replacement therapy (ERT) was
      administered, but she had frequent myoclonus and developmental regression. She
      needed artificial ventilation because of respiratory failure. She died at 11years
      of age. An autopsy demonstrated infiltrating CD68-positive large cells containing
      abundant lipids in alveoli, while in the liver, kidney and bone marrow CD68
      positive cells were small and round. In the bone marrow, myelodysplastic changes
      were present without Gaucher cells. The infiltration of Gaucher cells in alveoli
      was marked, suggesting that ERT was relatively ineffective in pulmonary
      involvement, particularly intra-alveolar. Additional treatments are necessary to
      improve the neurological and pulmonary prognosis of type 2Gaucher disease.

PMID- 27866811
TI  - The modified Glasgow prognosis score predicts for overall and disease-free
      survival following cytoreductive surgery and HIPEC in patients with pseudomyxoma
      peritonei of appendiceal origin.
AB  - BACKGROUND: The modified Glasgow prognostic score (incorporating C-reactive
      protein and albumin) predicts survival in patients with gastro-intestinal tract
      cancer but has not been evaluated in patients with peritoneal malignancy. The aim
      was to evaluate the modified Glasgow score preoperatively in patients undergoing
      complete cytoreductive surgery (CCRS) with hyperthermic intraperitoneal
      chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) of appendiceal origin.
      METHODS: Prospectively collected data from patients with PMP of appendiceal
      origin following CCRS and HIPEC between January 2007 and December 2011 were
      analysed. The mGPS was calculated from preoperative C-reactive protein and
      albumin. Predicted overall survival (OS) and disease-free survival (DFS) for each
      mGPS score were calculated using the Kaplan-Meier model. In a separate analysis,
      a comparison was made between mGPS and Tumour Markers (TM). RESULTS: 260 patients
      were included in the study. The mGPS of 0, 1, and 2 were found in 111, 130, and
      19 patients respectively. The median follow-up was 48 months. For mGPS-0, -1, and
      -2, the predicted OS was 82.2, 73.7, and 69.2 months and the DFS was 73.5, 62.9,
      and 54.4 months respectively. As mGPS increases, there is a reduction in long
      term survival. There was no difference between mGPS and TM. CONCLUSION:
      Preoperative mGPS may be a cost effective prognostic tool for predicting OS and
      DFS in patients following complete CRS-HIPEC, and performs well compared to TM
      for predicting patients at high risk of recurrence.

PMID- 27866812
TI  - A Case Report of Infectious Sacroiliitis in an Adult Presenting to the Emergency
      Department with Inability to Walk.
AB  - BACKGROUND: Infectious sacroiliitis (ISI) is an uncommon cause of back and hip
      pain in which the sacroiliac joint, either unilateral or bilateral, is inflamed
      from an infectious source. Historically, this has been an easily missed diagnosis
      due to nonspecific presenting symptoms along with subtle nondistinguishable
      laboratory abnormalities. CASE REPORT: We describe an injection drug user
      presenting with right-sided ISI who presented with hip and back pain and
      inability to walk. The patient had tenderness over his right sacroiliac joint,
      and despite negative plain radiographs, a magnetic resonance imaging (MRI) scan
      was obtained from the Emergency Department (ED) given the patient's risk factors
      for infection. Concerning findings of ISI on this MRI led to a computed
      tomography-guided biopsy during the patient's hospital admission, which revealed
      alpha-hemolytic Streptococcus as the responsible pathogen. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Infectious sacroiliitis is a rare
      condition that is difficult to diagnose, and carries increasing morbidity when
      diagnosis is delayed. We aim to increase awareness through a case report of a
      patient encountered in the ED.

PMID- 27866813
TI  - Rhodnius prolixus: from physiology by Wigglesworth to recent studies of immune
      system modulation by Trypanosoma cruzi and Trypanosoma rangeli.
AB  - This review is dedicated to the memory of Professor Sir Vincent B. Wigglesworth
      (VW) in recognition of his many pioneering contributions to insect physiology
      which, even today, form the basis of modern-day research in this field. Insects
      not only make vital contributions to our everyday lives by their roles in
      pollination, balancing eco-systems and provision of honey and silk products, but
      they are also outstanding models for studying the pathogenicity of microorganisms
      and the functioning of innate immunity in humans. In this overview, the immune
      system of the triatomine bug, Rhodnius prolixus, is considered which is most
      appropriate to this dedication as this insect species was the favourite subject
      of VW's research. Herein are described recent developments in knowledge of the
      functioning of the R. prolixus immune system. Thus, the roles of the cellular
      defences, such as phagocytosis and nodule formation, as well as the role of
      eicosanoids, ecdysone, antimicrobial peptides, reactive oxygen and nitrogen
      radicals, and the gut microbiota in the immune response of R. prolixus are
      described. The details of many of these were unknown to VW although his work
      gives indications of his awareness of the importance to R. prolixus of cellular
      immunity, antibacterial activity, prophenoloxidase and the gut microbiota. This
      description of R. prolixus immunity forms a backdrop to studies on the
      interaction of the parasitic flagellates, Trypanosoma cruzi and Trypanosoma
      rangeli, with the host defences of this important insect vector. These parasites
      remarkably utilize different strategies to avoid/modulate the triatomine immune
      response in order to survive in the extremely hostile host environments present
      in the vector gut and haemocoel. Much recent information has also been gleaned on
      the remarkable diversity of the immune system in the R. prolixus gut and its
      interaction with trypanosome parasites. This new data is reviewed and gaps in our
      knowledge of R. prolixus immunity are identified as subjects for future
      endeavours. Finally, the publication of the T. cruzi, T. rangeli and R. prolixus
      genomes, together with the use of modern molecular techniques, should lead to the
      enhanced identification of the determinants of infection derived from both the
      vector and the parasites which, in turn, could form targets for new molecular
      based control strategies.

PMID- 27866814
TI  - Predictors of tissue healing in ulcerative colitis patients treated with anti
      TNF.
AB  - AIM: To identify factors predicting mucosal healing in ulcerative colitis
      patients treated with anti-TNFalpha agents with or without azathioprine. METHODS:
      In a prospective, multicenter, one-year study biologic naive patients aged 25-65
      years, with corticosteroid-dependent or refractory colitis received combination
      treatment with anti-TNFalpha and azathioprine for 6 months followed by anti
      TNFalpha monotherapy. Patients who denied combination therapy or were outside
      this age range received anti-TNFalpha monotherapy (controls). Before and at weeks
      12 and 54 of treatment the total Mayo score was calculated. Mucosal healing was
      defined as endoscopic subscore of 0. Mucosal expression of T helper (Th) cell
      lineage specific transcription factors (Tbet, Gata3, Rorc, FoxP3) before
      treatment was also associated with mucosal healing. RESULTS: Of 67 patients, 58
      (86.6%) received combination and 9 (13.4%) anti-TNFalpha monotherapy. Overall 29
      (43.3%) patients achieved mucosal healing; rates were higher in patients
      receiving combination therapy vs. monotherapy (p=0.03) and in azathioprine naive
      vs. exposed patients in the combination group (p=0.01). Mucosal healing was
      associated with lower pre-treatment mucosal expression of transcription factor
      Th1-Tbet (p<0.05) and higher expression of Th17-Rorc (p<0.05). CONCLUSIONS:
      Mucosal healing was associated with combination therapy, especially in biologic
      and azathioprine-naive patients and pre-treatment mucosal expression of specific
      Th specific transcripting factors (Tbet and Rorc).

PMID- 27866816
TI  - Nitric oxide-donating derivatives of hederacolchiside A1: Synthesis and
      biological evaluation in vitro and in vivo as potential anticancer agents.
AB  - A series of nitric oxide (NO) donating derivatives of hederacolchiside A1 bearing
      triterpenoid saponin motif were designed, synthesized and evaluated for their
      anticancer activity. All of the tested furoxan-based NO releasing compounds
      showed significant proliferation inhibitory activities. Especially compound 6a
      exhibited strong cytotoxicity (IC50=1.6-6.5MUM) against four human tumor cell
      lines (SMMC-7721, NCI-H460, U251, HCT-116) in vitro and the highest level of NO
      releasing. Furthermore, compound 6a was revealed low acute toxicity to mice and
      weak haemolytic activity with potent tumor growth inhibition against mice H22
      hepatocellular cells in vivo (51.5%).

PMID- 27866815
TI  - N-[11CH3]Dimethylaminoparthenolide (DMAPT) uptake into orthotopic 9LSF
      glioblastoma tumors in the rat.
AB  - The aim of this study was to determine the uptake of intravenously administered N
      [11CH3]-dimethylaminoparthenolide (DMAPT) into orthotopic 9LSF glioblastoma brain
      tumors in Fisher 344 rats from positron emission tomography (PET) imaging
      studies. [11C]methyl iodide (11CH3I) was utilized as a [11C]-labeling reagent to
      label the precursor methylaminoparthenolide (MAPT) intermediate. From PET imaging
      studies it was found that brain uptake of N-[11CH3]DMAPT into brain tumor tissue
      was rapid (30min), and considerably higher than that in the normal brain tissue.

PMID- 27866817
TI  - Discovery of novel N-phenyl 1,4-dihydropyridines with a dual mode of
      antimycobacterial activity.
AB  - There is an urgent need for novel drugs for the treatment of tuberculosis (TB)
      due to the increasing prevalence of antibiotic resistance among Mycobacterium
      tuberculosis (Mtb) strains against first-line and second-line therapeutics. We
      developed novel N-phenyl 1,4-dihydropyridines as potential antituberculotic
      agents. The observed activity depends on the substitution patterns of the
      aromatic residues. N-unsubstituted 1,4-dihydropyridines are known inhibitors of
      the cancer-relevant transmembrane efflux pump ABCB1. Based on the similarity of
      ABCB1 amino acids sequences relevant to 1,4-dihydropyridine binding and the MTb
      efflux pump Rv0194, we determined ABCB1-inhibitory properties of our compounds in
      a cell line model. We identified one compound, which substantially increased the
      activity of two antituberculotic drugs which are substrates of ABCB1. The data
      indicate that our N-phenyl 1,4-dihydropyridines represent a novel compound class
      which improves the efficacy of anti-TB drugs by interfering with transmembrane
      efflux pumps in Mtb.

PMID- 27866818
TI  - The discovery of quinoline based single-ligand human H1 and H3 receptor
      antagonists.
AB  - A novel series of potent quinoline-based human H1 and H3 bivalent histamine
      receptor antagonists, suitable for intranasal administration for the potential
      treatment of allergic rhinitis associated nasal congestion, were identified.
      Compound 18b had slightly lower H1 potency (pA2 8.8 vs 9.7 for the clinical
      goldstandard azelastine), and H3 potency (pKi 9.1vs 6.8 for azelastine), better
      selectivity over alpha1A, alpha1B and hERG, similar duration of action, making
      18b a good back-up compound to our previous candidate, but with a more desirable
      profile.

PMID- 27866819
TI  - Endocrinology of human female sexuality, mating, and reproductive behavior.
AB  - Hormones orchestrate and coordinate human female sexual development, sexuality,
      and reproduction in relation to three types of phenotypic changes: life history
      transitions such as puberty and childbirth, responses to contextual factors such
      as caloric intake and stress, and cyclical patterns such as the ovulatory cycle.
      Here, we review the endocrinology underlying women's reproductive phenotypes,
      including sexual orientation and gender identity, mate preferences, competition
      for mates, sex drive, and maternal behavior. We highlight distinctive aspects of
      women's sexuality such as the possession of sexual ornaments, relatively cryptic
      fertile windows, extended sexual behavior across the ovulatory cycle, and a
      period of midlife reproductive senescence-and we focus on how hormonal mechanisms
      were shaped by selection to produce adaptive outcomes. We conclude with
      suggestions for future research to elucidate how hormonal mechanisms subserve
      women's reproductive phenotypes.

PMID- 27866820
TI  - Cutaneous fungal infections are commonly misdiagnosed: A survey-based study.

PMID- 27866821
TI  - Advanced Analysis Techniques Improve Infant Bone and Body Composition Measures by
      Dual-Energy X-Ray Absorptiometry.
AB  - OBJECTIVE: To evaluate a novel technique designed to reduce the negative impact
      of motion artifacts in infant dual-energy X-ray absorptiometry (DXA) scans. STUDY
      DESIGN: Using cross-sectional data from a large multicenter study, we developed
      and tested advanced methods for infant scan analysis. Newborns (n = 750) received
      spine and whole-body DXA scans with up to 3 attempts to acquire a motion free
      scan. Precision of infant DXA was estimated from visits with multiple valid
      scans. Accuracy of regional reflection, fusion, and omission techniques was
      estimated by comparing modified scans to unmodified valid scans. The
      effectiveness of the acquisition and analysis protocol was represented by the
      reduction in rate of failure to acquire valid results from infant visits.
      RESULTS: For infant whole-body DXA, arm reflection and all fusion techniques
      caused no significant changes to bone mineral content, bone mineral density, bone
      area, total mass, fat mass, lean mass, and percentage fat. Leg reflection and
      arm/leg dual-reflection caused significant changes to total mass, but the
      percentage change remained small. For infant spine DXA, fusion and omission
      caused no significant changes. Advanced analysis techniques reduced the failure
      rate of whole-body scanning from 20.8% to 9.3% and the failure rate of spine
      scanning from 8.9% to 2.4%. CONCLUSIONS: Advanced analysis techniques
      significantly reduced the impact of motion artifacts on infant DXA scans. We
      suggest this protocol be used in future infant DXA research and clinical
      practice.

PMID- 27866823
TI  - Relative Risk and Incidence for Developmental Dysplasia of the Hip.
AB  - OBJECTIVE: To determine the incidence and associated risk factors of
      developmental dysplasia of the hip (DDH) in a modern population without universal
      screening. STUDY DESIGN: Children with DDH were identified from the Manitoba
      Centre for Health Policy's Data Repository by the use of International
      Classification of Diseases diagnosis codes as well as physician billing tariffs
      for surgical procedures for DDH for all children born between 1995 and 2012. To
      identify the outpatient-treated patients, ultrasound scans and radiographic
      imaging for DDH were reviewed for 2004-2012. Overall incidence was calculated on
      the basis of birth rate for the province per year. Relative risks of sex, first
      born, breech position, clubfoot deformity, multiple gestations, as well as
      regional health areas were analyzed with chi2 tests. RESULTS: We identified 1716
      cases of DDH of 258 499 newborns. The incidence of DDH was calculated at 6.6/1000
      newborns. Late-presenting DDH was detected in 2.2/1000 newborns. Female first
      born children, clubfoot deformity, and breech position were associated
      significantly with an increased risk. Children with DDH born in rural areas of
      the Northern and Central part of Manitoba presented at a later age than those who
      are born in the urban areas (P < .0001) CONCLUSION: This study shows the need for
      improved early detection and awareness at well-baby clinics of risk factors and
      regional differences for DDH.

PMID- 27866822
TI  - Correlates of Physical Activity among Young Children with Moderate Acute
      Malnutrition.
AB  - OBJECTIVE: To assess the levels of physical activity among young children with
      moderate acute malnutrition and to identify clinical, biochemical,
      anthropometric, and sociodemographic correlates of physical activity. STUDY
      DESIGN: In a cross-sectional study, 1609 children aged 6-23 months wore a
      triaxial accelerometer (ActiGraph GT3x+; ActiGraph, Pensacola, Florida) for 6
      consecutive days, from which total physical activity were determined. Data on
      morbidity were collected based by history and physical examination, and serum C
      reactive protein and alpha1-acid glycoprotein were measured. RESULTS: A total of
      1544 (96%) children had physical activity measured, of whom 1498 (97%) completed
      6 consecutive days of physical activity recording with a daily median wear time
      of 24 hours. The mean (+/-SD) total physical activity was 707 (+/-180) vector
      magnitude counts per minute (cpm). Age was negatively correlated with physical
      activity; compared with children below 12 months of age, those 12-17 months of
      age, and 18-23 months of age had 51 (95% CI, 26; 75) and 106 (95% CI, 71; 141)
      cpm lower physical activity, respectively. Fever and malaria were associated with
      49 (95% CI, 27; 70) and 44 (95% CI, 27; 61) cpm lower activity, respectively.
      Elevated serum C-reactive protein and alpha1-acid glycoprotein were both negative
      correlates of physical activity, and hemoglobin was a positive correlate.
      CONCLUSIONS: Physical activity declines with age in children with moderate acute
      malnutrition and is also inversely related to infection and inflammatory status.
      Future studies are needed to ascertain cause and effect of these associations.
      TRIAL REGISTRATION: Controlled-Trials.com: ISRCTN42569496.

PMID- 27866824
TI  - Detection of Her2-overexpressing cancer cells using keyhole shaped chamber array
      employing a magnetic droplet-handling system.
AB  - An on-chip gene expression analysis compartmentalized in droplets was developed
      for detection of cancer cells at a single-cell level. The chip consists of a
      keyhole-shaped reaction chamber with hydrophobic modification employing a
      magnetic bead-droplet-handling system with a gate for bead separation. Using
      three kinds of water-based droplets in oil, a droplet with sample cells, a lysis
      buffer with magnetic beads, and RT-PCR buffer, parallel magnetic manipulation and
      fusion of droplets were performed using a magnet-handling device containing small
      external magnet patterns in an array. The actuation with the magnet offers a
      simple system for droplet manipulation that allows separation and fusion of
      droplets containing magnetic beads. After reverse transcription and amplification
      by thermal cycling, fluorescence was obtained for detection of overexpressing
      genes. For clinical detection of gastric cancer cells in peritoneal washing, the
      Her2-overexpressing gastric cancer cells spiked within normal cells was detected
      by gene expression analysis of droplets containing an average of 2.5 cells. Our
      developed droplet-based cancer detection system manipulated by external magnetic
      force without pumps or valves offers a simple and flexible set-up for
      transcriptional detection of cancer cells, and will be greatly advantageous for
      less-invasive clinical diagnosis and prognostic prediction.

PMID- 27866825
TI  - Comparative Effectiveness of Wellness Programs: Impact of Incentives on
      Healthcare Costs for Obese Enrollees.
AB  - INTRODUCTION: Employee wellness programs show mixed effectiveness results. This
      study examined the impact of an insurer's lifestyle modification program on
      healthcare costs of obese individuals. METHODS: This nonrandomized comparative
      effectiveness study evaluated changes in healthcare costs for participants in two
      incentivized programs, an Internet-mediated pedometer-based walking program
      (WalkingSpree, n=7,594) and an in-person weight-loss program (Weight Watchers,
      n=5,764). The primary outcome was the change in total healthcare costs from the
      baseline year to the year after program participation. Data were collected from
      2009 to 2011 and the analysis was done in 2014-2015. RESULTS: After 1 year,
      unadjusted mean costs decreased in both programs, with larger decreases for
      Weight Watchers participants than WalkingSpree participants (-$1,055.39 vs 
      $577.10, p=0.019). This difference was driven by higher rates of women in Weight
      Watchers, higher baseline total costs among women, and a greater decrease in
      costs for women in Weight Watchers (-$1,037.60 vs -$388.50, p=0.014). After
      adjustment for baseline costs, there were no differences by program or gender.
      CONCLUSIONS: Comparable cost reductions in both programs suggest that employers
      may want to offer more than one choice of incentivized wellness program with
      monitoring to meet the diverse needs of employees.

PMID- 27866826
TI  - The impact of online therapeutic feedback on outcome measures in Internet-CBTI
      for adolescents with insomnia.
AB  - BACKGROUND: Guided Internet cognitive behavioral therapy for insomnia (CBTI)
      offers an effective treatment for adolescents, but little is known about the
      active ingredients of therapeutic feedback on outcomes. OBJECTIVE: This study
      aims to identify which factors can be distinguished in written therapeutic
      feedback in Internet CBTI, and examine whether these factors and participation in
      a chat session contribute to sleep outcomes. METHODS: Internet CBTI was applied
      to 57 adolescents (mean age 15.43 years, SD 1.74, 82.5% girls). Symptoms of
      insomnia and chronic sleep reduction, and total sleep time, time in bed, and
      sleep efficiency from seven day sleep logs were measured at baseline, post
      treatment, and at two month follow-up. With a coding instrument developed for
      this study, two independent researchers coded transcripts of the written
      therapeutic feedback of the Internet CBTI sessions with an event sampling method.
      RESULTS: Principal component analysis of the initial 17 items from the coding
      instrument yielded four distinct factors of therapeutic feedback, of which only
      Sleep expertise seemed to contribute to improvements after Internet CBTI. The
      other factors, indicating forms of encouragement, and participation in a chat
      session seemed counterproductive. CONCLUSIONS: This first longitudinal study into
      effects of therapeutic feedback in adolescent Internet CBTI indicated that
      emphasizing knowledge about sleep might contribute to insomnia improvement. The
      structured nature of the preprogrammed treatment content, delay of therapeutic
      feedback due to standardized timing, and unintentional reinforcement of
      undesirable behavior by giving attention to failures might explain the negative
      results of encouraging behavior. Further research to identify effective
      therapeutic factors in Internet therapy is warranted.

PMID- 27866827
TI  - Nucleoprotein supplementation enhances the recovery of rat soleus mass with
      reloading after hindlimb unloading-induced atrophy via myonuclei accretion and
      increased protein synthesis.
AB  - Hindlimb unloading results in muscle atrophy and a period of reloading has been
      shown to partially recover the lost muscle mass. Two of the mechanisms involved
      in this recovery of muscle mass are the activation of protein synthesis pathways
      and an increase in myonuclei number. The additional myonuclei are provided by
      satellite cells that are activated by the mechanical stress associated with the
      reloading of the muscles and eventually incorporated into the muscle fibers.
      Amino acid supplementation with exercise also can increase skeletal muscle mass
      through enhancement of protein synthesis and nucleotide supplements can promote
      cell cycle activity. Therefore, we hypothesized that nucleoprotein
      supplementation, a combination of amino acids and nucleotides, would enhance the
      recovery of muscle mass to a greater extent than reloading alone after a period
      of unloading. Adult rats were assigned to 4 groups: control, hindlimb unloaded
      (HU; 14 days), reloaded (5 days) after hindlimb unloading (HUR), and reloaded
      after hindlimb unloading with nucleoprotein supplementation (HUR + NP). Compared
      with the HUR group, the HUR + NP group had larger soleus muscles and fiber cross
      sectional areas, higher levels of phosphorylated rpS6, and higher numbers of
      myonuclei and myogenin-positive cells. These results suggest that nucleoprotein
      supplementation has a synergistic effect with reloading in recovering skeletal
      muscle properties after a period of unloading via rpS6 activation and satellite
      cell differentiation and incorporation into the muscle fibers. Therefore, this
      supplement may be an effective therapeutic regimen to include in rehabilitative
      strategies for a variety of muscle wasting conditions such as aging, cancer
      cachexia, muscular dystrophy, bed rest, and cast immobilization.

PMID- 27866828
TI  - High-fat Western diet-induced obesity contributes to increased tumor growth in
      mouse models of human colon cancer.
AB  - Strong epidemiologic evidence links colon cancer to obesity. The increasing
      worldwide incidence of colon cancer has been linked to the spread of the Western
      lifestyle, and in particular consumption of a high-fat Western diet. In this
      study, our objectives were to establish mouse models to examine the effects of
      high-fat Western diet-induced obesity on the growth of human colon cancer tumor
      xenografts, and to examine potential mechanisms driving obesity-linked human
      colon cancer tumor growth. We hypothesize that mice rendered insulin resistant
      due to consumption of a high-fat Western diet will show increased and accelerated
      tumor growth. Homozygous Rag1tm1Mom mice were fed either a low-fat Western diet
      or a high-fat Western diet (HFWD), then human colon cancer xenografts were
      implanted subcutaneously or orthotopically. Tumors were analyzed to detect
      changes in receptor tyrosine kinase-mediated signaling and expression of
      inflammatory-associated genes in epididymal white adipose tissue. In both models,
      mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor
      weight was greater compared with in the low-fat Western diet-fed mice. They also
      displayed significantly higher levels of leptin; however, there was a negative
      correlation between leptin levels and tumor size. In the orthotopic model, tumors
      and adipose tissue from the HFWD group displayed significant increases in both c
      Jun N-terminal kinase activation and monocyte chemoattractant protein 1
      expression, respectively. In conclusion, this study suggests that human colon
      cancer growth is accelerated in animals that are obese and insulin resistant due
      to the consumption of an HFWD.

PMID- 27866829
TI  - Lutein and zeaxanthin supplied by red/orange foods and fruits are more closely
      associated with macular pigment optical density than those from green vegetables
      in Spanish subjects.
AB  - Lutein and zeaxanthin (L+Z) accumulate in the retina. Although vegetables are
      major contributors to their intake, a stronger association between fruits and
      macular pigment optical density (MPOD) has been reported. We hypothesized that
      L+Z intake from fruits would have a stronger association with L+Z status markers
      (MPOD, serum concentrations) than intake from vegetables or eggs, and that those
      associations would also differ according to plant foods color. One hundred eight
      subjects (57 men; age groups, 20-35 and 45-65 years) were enrolled in a cross
      sectional study. L+Z intake from fruits, vegetables, and eggs was determined
      using three 24-hour diet recalls and a country-specific carotenoid database.
      Vegetables were the major contributors (75%) to L+Z intake, followed by eggs
      (10%) and fruits (4%). Vegetables supplied 86% and 84% of the LandZ intake,
      respectively, and fruits supplied 3% and 16%. Green foods supplied 78% and 52% of
      LandZ, respectively, followed by red/orange (9% and 38%) and white/yellow (14%
      and 9%). Factorial analysis showed associations in older subjects. The explained
      variance of the first 2 principal components was 54% considering L+Z intake from
      fruits, vegetables, and eggs, and 55% considering L+Z intake from plant foods
      grouped by color. Macular pigment optical density is related to L+Z intake from
      fruits (0.264, P=.003) and is independent of that from vegetables and eggs. It is
      related to L+Z intake from red/orange foods (0.320, P=.000) and the serum
      concentrations to that from green foods (0.222, P=.11). Although vegetables and
      green foods of plant origin are the major contributors to L+Z intake, red/orange
      foods and fruits have the strongest relationship to MPOD in study participants
      (45-65 years of age).

PMID- 27866831
TI  - The debate: Treatment after the first seizure - The CONTRA.
AB  - In many instances antiepileptic drug (AED) treatment of epilepsy patients is
      sustained for a long time and is even a lifelong therapy. Chronic drug treatment
      naturally means the potential burden of adverse effects. The prognosis to remain
      seizure-free is good after a first seizure even without AEDs. Therefore one has
      to consider the possibility that freedom from seizures when AED treatment has
      been initiated after the first seizure may not in fact be the result of the AED
      treatment. On the other hand seizure-free patients without severe side effects
      most probably will not consider discontinuing AEDs. Therefore in these cases it
      will not be possible to discover whether AEDs are really necessary to maintain
      freedom from seizures. Furthermore it has been shown that the long-term prognosis
      is independent of whether AED treatment started after the first or a following
      seizure. Therefore in most instances AED treatment after a first seizure should
      be avoided.

PMID- 27866830
TI  - A high-fat diet differentially regulates glutathione phenotypes in the obesity
      prone mouse strains DBA/2J, C57BL/6J, and AKR/J.
AB  - The ubiquitous tripeptide glutathione (GSH) is a critical component of the
      endogenous antioxidant defense system. Tissue GSH concentrations and redox status
      (GSH/GSSG) are genetically controlled, but it is unclear whether interactions
      between genetic background and diet affect GSH homeostasis. The current study
      tested the hypothesis that a high-fat diet regulates GSH homeostasis in a manner
      dependent on genetic background. At 4 months of age, female mice representing 3
      obesity-prone inbred strains-C57BL/6J (B6), DBA/2J (D2), and AKR/J (AKR)-were
      randomly assigned to consume a control (10% energy from fat) or high-fat (62%
      energy from fat) diet for 10 weeks (n=5/diet per strain). Tissue GSH levels, GSSG
      levels, and GSH/GSSG were quantified, and hepatic expression of GSH-related
      enzymes was evaluated by quantitative reverse transcription polymerase chain
      reaction. The high-fat diet caused a decrease in hepatic GSH/GSSG in D2 mice. In
      contrast, B6 mice exhibited a decrease in GSSG levels in the liver and kidney, as
      well as a resultant increase in renal GSH/GSSG. AKR mice also exhibited increased
      renal GSH/GSSG on a high-fat diet. Finally, the high-fat diet induced a unique
      gene expression response in D2 mice compared with B6 and AKR. The D2 response was
      characterized by up-regulation of glutamate-cysteine ligase modifier subunit and
      down-regulation of glutathione reductase, whereas the B6 and AKR responses were
      characterized by up-regulation of glutathione peroxidase 1. Two-way analysis of
      variance analyses confirmed several diet-strain interactions within the GSH
      system, and linear regression models highlighted relationships between body mass
      and GSH outcomes as well. Overall, our data indicate that dietary fat regulates
      the GSH system in a strain-dependent manner.

PMID- 27866833
TI  - TP53 and 53BP1 Reunited.
AB  - Identified as a TP53-binding protein, 53BP1 is a key regulator of the cellular
      response to double-strand breaks, a TP53-independent activity. Recent data have
      established a new TP53-dependent function for 53BP1 in mitotic surveillance after
      centrosome loss.

PMID- 27866832
TI  - Roscoe Owen Brady, MD: Remembrances of co-investigators and colleagues.
AB  - To celebrate the research visions and accomplishments of the late Roscoe O. Brady
      (1923-2016), remembrance commentaries were requested from several of his
      postdoctoral research fellows and colleagues. These commentaries not only reflect
      on the accomplishments of Dr. Brady, but they also share some of the backstories
      and experiences working in the Brady laboratory. They provide insights and
      perspectives on Brady's research activities, and especially on his efforts to
      develop an effective treatment for patients with Type 1 Gaucher disease. These
      remembrances illuminate Brady's efforts to implement the latest scientific
      advances with an outstanding team of young co-investigators to develop and
      demonstrate the safety and effectiveness of the first enzyme replacement therapy
      for a lysosomal storage disease. Brady's pursuit and persistence in accomplishing
      his research objectives provide insights into this remarkably successful
      physician scientist who paved the way for the development of treatments for
      patients with other lysosomal storage diseases.

PMID- 27866834
TI  - 'Patient 0' and the Origin of HIV/AIDS in America.
AB  - The origin of the HIV/AIDS epidemic in North America remains contentious. A
      recent study uses phylogenetic and historical approaches to investigate the early
      history of HIV-1 group M subtype B in North America and shows that 'Patient 0' is
      not the source of the North American HIV/AIDS epidemic.

PMID- 27866835
TI  - Over-using chemotherapy in the adjuvant setting.
AB  - Avoidance of unnecessary or ineffective treatment should be one of the main goals
      in adjuvant breast oncology today. Unfortunately, both patients and doctors hunt
      for tiny statistical differences in survival curves. This search could not only
      lead to an oncological approach of unlimited addition that we will not be able to
      afford, but would also end inevitably in indeterminate overtreatment with
      substantial risks of unexpected toxic effects eating away whatever progress we
      might make. "Do not harm" remains the main principle in medicine. To be able to
      follow this rule, we need to better understand the biology of breast cancer. The
      mistake of "one treatment fits all" can only be changed when we critically review
      trial designs of adjuvant breast oncology. The risk of overtreatment is there and
      selection of precisely defined cohorts for phase 3 trials is necessary, despite
      pressure of scientific ambition, pragmatism, and demands of industry. The "add
      on" clinical trial design model accepts the inability to confirm that standard
      therapy is still necessary if a positive result from the addition of the new
      therapy is obtained. The same model can be applied to "extended" adjuvant
      treatments in breast cancer subtypes. Addition of "miraculin" to the standard of
      care should generate a new standard. Such trials that show a modest benefit on
      average at a population level take us a step away from refining care for the
      individual, and might support the use of multiple and costly interventions with
      potential short and long term side effects. It is essential to escalate treatment
      when necessary and to de-escalate when un-necessary.

PMID- 27866836
TI  - Physiological Suppression of Lipotoxic Liver Damage by Complementary Actions of
      HDAC3 and SCAP/SREBP.
AB  - Liver fat accumulation precedes non-alcoholic steatohepatitis, an increasing
      cause of end-stage liver disease. Histone deacetylase 3 (HDAC3) is required for
      hepatic triglyceride homeostasis, and sterol regulatory element binding protein
      (SREBP) regulates the lipogenic response to feeding, but the crosstalk between
      these pathways is unknown. Here we show that inactivation of SREBP by hepatic
      deletion of SREBP cleavage activating protein (SCAP) abrogates the increase in
      lipogenesis caused by loss of HDAC3, but fatty acid oxidation remains defective.
      This combination leads to accumulation of lipid intermediates and to an energy
      drain that collectively cause oxidative stress, inflammation, liver damage, and,
      ultimately, synthetic lethality. Remarkably, this phenotype is prevented by
      ectopic expression of nuclear SREBP1c, revealing a surprising benefit of de novo
      lipogenesis and triglyceride synthesis in preventing lipotoxicity. These results
      demonstrate that HDAC3 and SCAP control symbiotic pathways of liver lipid
      metabolism that are critical for suppression of lipotoxicity.

PMID- 27866837
TI  - High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via
      Passive Cholesterol Depletion and PKC-NF-kappaB/STAT1-IRF1 Signaling.
AB  - Membrane cholesterol modulates a variety of cell signaling pathways and
      functions. While cholesterol depletion by high-density lipoproteins (HDLs) has
      potent anti-inflammatory effects in various cell types, its effects on
      inflammatory responses in macrophages remain elusive. Here we show overt pro
      inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft
      disruption in murine and human primary macrophages in vitro. These pro
      inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I
      transgenic mice, which have elevated HDL levels. In line with these findings, the
      innate immune responses required for clearance of P. aeruginosa bacterial
      infection in lung were compromised in mice with low HDL levels. Expression
      analysis, ChIP-PCR, and combinatorial pharmacological and genetic intervention
      studies unveiled that both native and reconstituted HDL enhance Toll-like
      receptor-induced signaling by activating a PKC-NF-kappaB/STAT1-IRF1 axis, leading
      to increased inflammatory cytokine expression. HDL's pro-inflammatory activity
      supports proper functioning of macrophage immune responses.

PMID- 27866839
TI  - Markers for toxicity to HepG2 exposed to cadmium sulphide quantum dots; damage to
      mitochondria.
AB  - Interaction of living organisms with quantum dots (QDs) is certainly more focused
      on environment and occupational exposure associated with production and release
      or disposal. Here, the transcription of genes involved in mitochondrial
      organization and function in HepG2 cells exposed to cadmium sulphide (CdS) QDs
      has been profiled to highlight biomarkers of exposure and effect to be tested for
      other cadmium based QDs. At low concentrations, exposure to CdS QDs induced only
      minor damage to nuclear DNA, and none to mitochondrial DNA. However, the stress
      caused an increase in the production of reactive oxygen species (ROS), which
      triggered the mitochondria-mediated intrinsic apoptotic pathway involving a
      cascade of transcriptomic events, finally prompting the activation of a rescue
      pathway. The transcriptomic analysis confirmed the involvement in the response to
      CdS QDs of genes related to apoptosis (AIFM2 and APAF1), oxidative stress
      response (OXR1 and AOX1) and autophagy (ATG3 and ATG7), as potential biomarkers.
      Other possible biomarkers specific for mitochondria function were LONP1 and
      HSPD1.

PMID- 27866838
TI  - Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic
      Programs in Trained Immunity.
AB  - Induction of trained immunity (innate immune memory) is mediated by activation of
      immune and metabolic pathways that result in epigenetic rewiring of cellular
      functional programs. Through network-level integration of transcriptomics and
      metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol
      synthesis pathway as indispensable for the induction of trained immunity by beta
      glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of
      the TCA cycle, integrates immune and metabolic circuits to induce monocyte
      epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore,
      fumarate itself induced an epigenetic program similar to beta-glucan-induced
      trained immunity. In line with this, inhibition of glutaminolysis and cholesterol
      synthesis in mice reduced the induction of trained immunity by beta-glucan.
      Identification of the metabolic pathways leading to induction of trained immunity
      contributes to our understanding of innate immune memory and opens new
      therapeutic avenues.

PMID- 27866840
TI  - The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to
      acquired idiopathic thrombotic thrombocytopenic purpura.
AB  - The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an
      autoimmune disease, in which the underlying ADAMTS13-deficiency is caused by
      inhibitory autoantibodies against the protease. Human leukocyte antigens (HLA),
      responsible for antigen presentation, play an important role in the development
      of antibodies. The loci coding HLA DR and DQ molecules are inherited in linkage
      as haplotypes. The c.1858C>T polymorphism of the PTPN22 gene, which codes a
      protein tyrosine phosphatase important in lymphocyte activation, predisposes to a
      number of autoimmune diseases. We determined the HLA-DRB1-DQB1 haplotypes and the
      PTPN22 c.1858C>T genotypes in 75 patients with acquired idiopathic TTP and in
      healthy controls, in order to assess the role of these genetic factors and their
      interactions in the susceptibility to TTP. We found that the carrier frequencies
      of the DRB1*11-DQB1*03 and DRB1*15-DQB1*06 haplotypes were higher, while those of
      the DRB1*07-DQB1*02 and DRB1*13-DQB1*06 haplotypes were lower in TTP patients.
      There was no difference in the overall frequency of the PTPN22 c.1858T allele
      between TTP patients and controls. In conclusion, we identified four HLA-DRB1
      DQB1 haplotypes associated with an increased (DRB1*11-DQB1*03 and DRB1*15
      DQB1*06) or a decreased (DRB1*07-DQB1*02 and DRB1*13-DQB1*06) susceptibility to
      acquired idiopathic TTP.

PMID- 27866841
TI  - Thai Yoga improves physical function and well-being in older adults: A randomised
      controlled trial.
AB  - OBJECTIVES: Compare two 12-week low-intensity exercise regimens on components of
      physical function and quality of life in community-dwelling healthy yet sedentary
      adults aged over 60. DESIGN: This study used a randomised, multi-arm, controlled
      trial design. METHODS: Thirty-nine sedentary participants (29 women), aged 67.7+/
      6.7 years were randomly allocated to either a 12-week Thai Yoga (TY) or Tai Chi
      (TC) for 90min twice per week, or telephone counselling Control (C). A Senior
      Fitness Test (chair-stand, arm-curl, sit-&-reach, back-scratch, 8-foot up-&-go
      and 6-min walk) and Short-Form 36 Health Survey, Centre for Epidemiological
      Studies of Depression, Physical Activity Scale for the Elderly and the Physical
      Activity Enjoyment Scale were assessed at baseline, six, 12 weeks, and three
      months after the completion of the regimen. RESULTS: After 12 weeks, chair-stand
      (mean difference, 2.69; 95% CI, 0.97-4.41; P<0.001), arm-curl (2.23; 95% CI, 0.06
      4.52; P=0.009), sit-&-reach (1.25; 95% CI, 0.03-2.53; P=0.013), back-scratch
      (2.00; 95% CI, 0.44-3.56; P=0.005), 8-foot up-&-go (-0.43; 95% CI, -0.85 to 0.01;
      P=0.013), 6-min walk (57.5; 95% CI, 20.93-94.07; P<0.001), vitality (13.27; 95%
      CI, 2.88-23.66; P=0.050) and enjoyment (7.96; 95% CI, 3.70-12.23; P=0.001)
      significantly improved in TY compared to C, however no change was observed in TC
      compared to C. TY improved in chair-stand (2.31; 95% CI, 0.59-4.03; P=0.007), sit
      &-reach (1.38; 95% CI, 0.10-2.66; P=0.007), 6-min walk (32.31; 95% CI, -4.26
      68.88; P=0.015), vitality (12.88; 95% CI, 2.50-23.27; P=0.040) and enjoyment
      (5.65; 95% CI, 1.39-9.92; P=0.010) compared to TC after 12 weeks. CONCLUSIONS:
      The findings suggest that older adults can make significant improvements in their
      health and well-being by engaging in low intensity Thai Yoga exercise.

PMID- 27866842
TI  - Upholding Rigorous Standards: Comparable Patterns and Rates of Recurrence Between
      Open and Robot-assisted Radical Cystectomy.

PMID- 27866843
TI  - Postoperative Radiotherapy in Locally Advanced Prostate Cancer: A Question of Who
      and When.

PMID- 27866844
TI  - New materials for sample preparation techniques in bioanalysis.
AB  - The analysis of biological samples is a complex and difficult task owing to two
      basic and complementary issues: the high complexity of most biological matrices
      and the need to determine minute quantities of active substances and contaminants
      in such complex sample. To succeed in this endeavor samples are usually subject
      to three steps of a comprehensive analytical methodological approach: sample
      preparation, analytes isolation (usually utilizing a chromatographic technique)
      and qualitative/quantitative analysis (usually with the aid of mass spectrometric
      tools). Owing to the complex nature of bio-samples, and the very low
      concentration of the target analytes to be determined, selective sample
      preparation techniques is mandatory in order to overcome the difficulties imposed
      by these two constraints. During the last decade new chemical synthesis
      approaches has been developed and optimized, such as sol-gel and molecularly
      imprinting technologies, allowing the preparation of novel materials for sample
      preparation including graphene and derivatives, magnetic materials, ionic
      liquids, molecularly imprinted polymers, and much more. In this contribution we
      will review these novel techniques and materials, as well as their application to
      the bioanalysis niche.

PMID- 27866845
TI  - Untargeted serum metabolomics reveals Fu-Zhu-Jiang-Tang tablet and its optimal
      combination improve an impaired glucose and lipid metabolism in type II diabetic
      rats.
AB  - Fu-Zhu-Jiang-Tang tablet, a six-herb preparation, was proved to show beneficial
      effects on type II diabetes patients in clinical. This study aims to optimize the
      component proportion of the six-herb preparation and explore the serum metabolic
      signatures of type II diabetes rats after treatment with Fu-Zhu-Jiang-Tang tablet
      and its optimal combination. The component proportion of the preparation was
      optimized using uniform experimental design and machine learning techniques.
      Untargeted GC-MS metabolomic experiments were carried out with serum samples from
      model group and treatment groups. Data were normalized, multivariate and
      univariate statistical analysis performed and metabolites of interest putatively
      identified. 23 metabolites were significantly changed by Fu-Zhu-Jiang-Tang tablet
      treatment and the majority of these were decreased, including various
      carbohydrates (glucose, mannose, fructose, allose and gluconic acid), unsaturated
      fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid, arachidonic acid),
      alanine, valine, propanoic acid, 3-hydroxybutyrate, along with pyrimidine and
      cholesterol. Increased concentrations of oxalic acid, leucine, glycine, serine,
      threonine, proline, lysine and citrate were observed. In the optimal combination
      fed group, 21 metabolites were significantly affected and strikingly, the
      magnitudes of changes here were generally much greater than that of Fu-Zhu-Jiang
      Tang tablet treated rats. 18 metabolites affected in both groups included various
      carbohydrates (mannose, glucose, allose, fructose and gluconic acid), unsaturated
      fatty acids (palmitic acid, 9-octadecenoic acid, oleic acid and arachidonic
      acid), short-chain fatty acids (oxalic acid, 3-hydroxybutyrate), and amino acids
      (alanine, valine, leucine, glycine, proline and lysine), as well as pyrimidine.
      Metabolites exclusively affected in optimal combination treated rat included
      succinic acid, cysteine and phenylalanine, whilst four metabolites (propanoic
      acid, citrate, serine and threonine) were only altered in Fu-Zhu-Jiang-Tang
      tablet treated rat. Our investigation demonstrated Fu-Zhu-Jiang-Tang tablet and
      its optimal combination treatments were able to ameliorate impaired glucose and
      lipid metabolism, down- regulate the high level of glucose to a lower level and
      reverse abnormal levels of metabolites in serum of type II diabetes rats.
      However, the optimal combination treatment was able to maximize the magnitudes of
      changes in some metabolites. These findings may be helpful in clarifying the anti
      diabetic mechanism of FZJT tablet and its optimal combination.

PMID- 27866846
TI  - Determination of enantiomeric vigabatrin by derivatization with diacetyl-l
      tartaric anhydride followed by ultra-high performance liquid chromatography
      quadrupole-time-of-flight mass spectrometry.
AB  - Vigabatrin, one of the most widely used antiepileptic drugs, is marketed and
      administered as a racemic mixture, while only S-enantiomer is therapeutically
      effective. In the present study, diacetyl-l-tartaric acid anhydride was used as
      an inexpensive and effective chiral derivatization reagent to produce tartaric
      acid monoester derivatives of vigabatrin enantiomers that could be readily
      resolved by reversed phase chromatography. Derivatization conditions were
      statistically optimized by response surface methodology, resulting in an optimal
      reaction temperature of 44 degrees C and an optimal reaction time of 30min. The
      derivatized diastereomers of vigabatrin and internal standard (gabapentin) were
      analyzed using ultra-high performance liquid chromatography coupled to quadrupole
      time-of-flight mass spectrometry. For this analysis, an Agilent ZORBAX Rapid
      Resolution High Definition Eclipse Plus C18 column (100mm*2.1mm, 1.8MUm) was
      employed for chromatographic separation using 10mM ammonium formate (pH 3.0) and
      methanol as mobile phase at a flow rate of 0.2mLmin-1. The established method was
      validated in terms of specificity, linearity, precision, accuracy, dilution
      integrity, recovery, matrix effect, stability, and incurred sample reanalysis. It
      was linear over a range of 0.25-100.0mgL-1 for both S- and R-enantiomers
      (R2>=0.9987 for both). Intra- and inter-day precisions and accuracies were within
      acceptable ranges. The method was successfully applied to determine the levels of
      vigabatrin enantiomers in mouse serum after administration of vigabatrin
      racemate.

PMID- 27866847
TI  - Detection of trans-fatty acids by high performance liquid chromatography coupled
      with in-tube solid-phase microextraction using hydrophobic polymeric monolith.
AB  - Based on in-tube solid-phase microextraction (in-tube SPME) using a hydrophobic
      poly (octadecyl methacrylate-co-ethylene dimethacrylate) [poly (OMA-co-EDMA)]
      monolith, a simple high performance liquid chromatography (HPLC) method has been
      developed for detection of trans-fatty acids (TFAs) as their fatty acid methyl
      esters (FAMEs). The poly (OMA-co-EDMA) monolithic column with high hydrophobicity
      was specially prepared for simultaneous microextraction, pre-separation and
      purification for the analytes. The pre-separation selectivity, the extraction
      efficiency, and the purification effect for FAMEs were investigated respectively.
      Furthermore, some operation parameters have been optimized in detail with respect
      to satisfactory extraction efficiency of the target compounds. Under the
      optimized conditions, the enrichment factors for model FAMEs were ranged from
      58.3 to 70.9, wide linear range (0.01-1.00mg/kg) and low detection limits (LODs)
      (3.0-7.1MUg/kg) were achieved, respectively. In addition, recoveries of the
      method were in the range from 83.0 to 106.4% with low relative standard
      deviations (RSDs) of 3.2-4.7% (n=4) at spiking levels of 0.05, 0.25 and 0.5mg/kg,
      respectively. Finally, the proposed method was successfully applied for detection
      of TFAs in practical samples, which possesses short time-consuming, low
      disturbance and high detection sensitivity.

PMID- 27866848
TI  - Analysis of GTV reduction during radiotherapy for oropharyngeal cancer:
      Implications for adaptive radiotherapy.
AB  - BACKGROUND AND PURPOSE: Adaptive field size reduction based on gross tumor volume
      (GTV) shrinkage imposes risk on coverage. Fiducial markers were used as surrogate
      for behavior of tissue surrounding the GTV edge to assess this risk by evaluating
      if GTVs during treatment are dissolving or actually shrinking. MATERIALS AND
      METHODS: Eight patients with oropharyngeal tumors treated with chemo-radiation
      were included. Before treatment, fiducial markers (0.035*0.2cm2, n=40) were
      implanted at the edge of the primary tumor. All patients underwent planning-CT,
      daily cone beam CT (CBCT) and MRIs (pre-treatment, weeks 3 and 6). Marker
      displacement on CBCT was compared to local GTV surface displacement on MRIs.
      Additionally, marker displacement relative to the GTV surfaces during treatment
      was measured. RESULTS: GTV surface displacement derived from MRI was larger than
      derived from fiducial markers (average difference: 0.1cm in week 3). During
      treatment, the distance between markers and GTV surface on MRI in week 3
      increased in 33%>0.3cm and in 10%>0.5cm. The MRI-GTV shrank faster than the
      surrounding tissue represented by the markers, i.e. adapting to GTV shrinkage may
      cause under-dosage of microscopic disease. CONCLUSIONS: We showed that adapting
      to primary tumor GTV shrinkage on MRI mid-treatment is potentially not safe since
      at least part of the GTV is likely to be dissolving. Adjustment to clear
      anatomical boundaries, however, may be done safely.

PMID- 27866849
TI  - Inter-observer variation in delineating the coronary arteries as organs at risk.
AB  - PURPOSE: To determine the inter-observer variation in delineating the coronary
      arteries as organs at risk (OAR) in breast cancer (BC) radiotherapy (RT) and how
      this variation affects the estimated coronary artery radiation dose. METHOD:
      Delineation of the left main and the left anterior descending coronary artery
      (LMCA and LAD), and the right coronary artery (RCA), by using the heart atlas by
      Feng et al., was performed by three radiation oncologists in 32 women who had
      received adjuvant RT for BC. Centres of the arteries were calculated and
      distances between artery centres were measured and the artery radiation doses
      were estimated. The intraclass correlation coefficient (ICC) was used to quantify
      the variability in doses. RESULTS: Along the extent of RCA, the median distance
      between centres of arteries varied from 2 to 9mm with similar patterns over pairs
      of oncologists. For the LMCA-LAD the median distance varied from 1 to 4mm. The
      estimated maximum radiation doses showed an ICC variation from 0.82 to 0.97.
      CONCLUSION: The coronary arteries can be reliably identified and delineated as
      OARs in BC RT. The spatial variance is limited and the total variation in
      radiation dose is almost completely determined by the between patient variation.

PMID- 27866850
TI  - Deubiquitination and Stabilization of PD-L1 by CSN5.
AB  - Pro-inflammatory cytokines produced in the tumor microenvironment lead to
      eradication of anti-tumor immunity and enhanced tumor cell survival. In the
      current study, we identified tumor necrosis factor alpha (TNF-alpha) as a major
      factor triggering cancer cell immunosuppression against T cell surveillance via
      stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that
      COP9 signalosome 5 (CSN5), induced by NF-kappaB p65, is required for TNF-alpha
      mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination
      and degradation of PD-L1. Inhibition of CSN5 by curcumin diminished cancer cell
      PD-L1 expression and sensitized cancer cells to anti-CTLA4 therapy.

PMID- 27866852
TI  - OmpA: A Flexible Clamp for Bacterial Cell Wall Attachment.
AB  - The envelope of Gram-negative bacteria is highly complex, containing separate
      outer and inner membranes and an intervening periplasmic space encompassing a
      peptidoglycan (PGN) cell wall. The PGN scaffold is anchored non-covalently to the
      outer membrane via globular OmpA-like domains of various proteins. We report
      atomically detailed simulations of PGN bound to OmpA in three different states,
      including the isolated C-terminal domain (CTD), the full-length monomer, or the
      complete full-length dimeric form. Comparative analysis of dynamics of OmpA CTD
      from different bacteria helped to identify a conserved PGN-binding mode. The
      dynamics of full-length OmpA, embedded within a realistic representation of the
      outer membrane containing full-rough (Ra) lipopolysaccharide, phospholipids, and
      cardiolipin, suggested how the protein may provide flexible mechanical support to
      the cell wall. An accurate model of the heterogeneous bacterial cell envelope
      should facilitate future efforts to develop antibacterial agents.

PMID- 27866851
TI  - Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel
      Normalization, Impairs Metastasis, and Improves Chemotherapy.
AB  - Abnormal tumor vessels promote metastasis and impair chemotherapy. Hence, tumor
      vessel normalization (TVN) is emerging as an anti-cancer treatment. Here, we show
      that tumor endothelial cells (ECs) have a hyper-glycolytic metabolism, shunting
      intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the
      glycolytic activator PFKFB3 did not affect tumor growth, but reduced cancer cell
      invasion, intravasation, and metastasis by normalizing tumor vessels, which
      improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition
      tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs, and
      rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin)
      through glycolysis reduction; it also lowered the expression of cancer cell
      adhesion molecules in ECs by decreasing NF-kappaB signaling. PFKFB3-blockade
      treatment also improved chemotherapy of primary and metastatic tumors.

PMID- 27866854
TI  - Source apportionment of fine and coarse particles at a roadside and urban
      background site in London during the 2012 summer ClearfLo campaign.
AB  - London, like many major cities, has a noted air pollution problem, and a better
      understanding of the sources of airborne particles in the different size
      fractions will facilitate the implementation and effectiveness of control
      strategies to reduce air pollution. Thus, the trace elemental composition of the
      fine and coarse fraction were analysed at hourly time resolution at urban
      background (North Kensington, NK) and roadside (Marylebone Road, MR) sites within
      central London. Unlike previous work, the current study focuses on measurements
      during the summer providing a snapshot of contributing sources, utilising the
      high time resolution to improve source identification. Roadside enrichment was
      observed for a large number of elements associated with traffic emissions (Al, S,
      Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, As, Rb and Zr), while those elements that are
      typically from more regional sources (e.g. Na, Cl, S and K) were not found to
      have an appreciable increment. Positive Matrix Factorization (PMF) was applied
      for the source apportionment of the particle mass at both sites with similar
      sources being identified, including sea salt, airborne soil, traffic emissions,
      secondary inorganic aerosols and a Zn-Pb source. In the fine fraction, traffic
      emissions was the largest contributing source at MR (31.9%), whereas it was
      incorporated within an "urban background" source at NK, which had contributions
      from wood smoke, vehicle emissions and secondary particles. Regional sources were
      the major contributors to the coarse fraction at both sites. Secondary inorganic
      aerosols (which contained influences from shipping emissions and coal combustion)
      source factors accounted for around 33% of the PM10 at NK and were found to have
      the highest contributions from regional sources, including from the European
      mainland. Exhaust and non-exhaust sources both contribute appreciably to PM10
      levels at the MR site, highlighting the continuing importance of vehicle-related
      air pollutants at roadside.

PMID- 27866853
TI  - Functional Annotation of Ion Channel Structures by Molecular Simulation.
AB  - Ion channels play key roles in cell membranes, and recent advances are yielding
      an increasing number of structures. However, their functional relevance is often
      unclear and better tools are required for their functional annotation. In sub
      nanometer pores such as ion channels, hydrophobic gating has been shown to
      promote dewetting to produce a functionally closed (i.e., non-conductive) state.
      Using the serotonin receptor (5-HT3R) structure as an example, we demonstrate the
      use of molecular dynamics to aid the functional annotation of channel structures
      via simulation of the behavior of water within the pore. Three increasingly
      complex simulation analyses are described: water equilibrium densities; single
      ion free-energy profiles; and computational electrophysiology. All three
      approaches correctly predict the 5-HT3R crystal structure to represent a
      functionally closed (i.e., non-conductive) state. We also illustrate the
      application of water equilibrium density simulations to annotate different
      conformational states of a glycine receptor.

PMID- 27866855
TI  - Possible emissions of POPs in plain and hilly areas of Nepal: Implications for
      source apportionment and health risk assessment.
AB  - Ambient air is a core media chosen for monitoring under the Stockholm Convention
      on POPs. While extensive monitoring of POPs in ambient air has been carried out
      in some parts of the globe, there are still regions with very limited information
      available, such as some developing countries as Nepal. This study therefore aims
      to target the occurrence of selected POPs in Nepal in suspected source areas/more
      densely populated regions. Four potential source regions in Nepal were
      furthermore targeted as it was hypothesized that urban areas at lower altitudes
      (Birgunj and Biratnagar located at approximately 86 and 80 m.a.s.l.) would be
      potentially more affected by OCPs because of more intensive agricultural
      activities in comparison to urban areas at higher altitudes (Kathmandu, Pokhara
      located 1400 and 1135 m.a.s.l). As some of these areas could also be impacted by
      LRAT, air mass back trajectories during the sampling period were additionally
      evaluated using HYSPLIT. The concentrations of overall POPs were twice as high in
      plain areas in comparison to hilly areas. DDTs and HCHs were most frequently
      detected in the air samples. The high p,p'-DDT/(pp'-DDE + pp'-DDD) ratio as well
      as the low o,p'-DDT/p,p'-DDT ratio observed in this study was inferred as
      continuing use of technical DDT. High levels of ?26PCBs were linked to proximity
      to highly urbanized and industrial areas, indicating the potential source of
      PCBs. The measured concentrations of legacy POPs in air from this study is
      assumed to represent a negligible health risk through inhalation of ambient air,
      however, other modes of human exposure could still be relevant in Nepal. The air
      mass backward trajectory analysis revealed that most of the air masses sampled
      originated from India and the Bay of Bengal.

PMID- 27866856
TI  - Free tissue transfer in patients with sickle cell disease: Considerations for
      multi-disciplinary peri-operative management.
AB  - INTRODUCTION AND AIMS: Sickle cell disease (SCD) is an increasingly common
      condition in the UK. The safety of free tissue transfer in these patients is
      controversial, and no specific guidelines exist. The aim of this paper is to
      create recommendations for the plastic surgical multidisciplinary team for use in
      the assessment and management of SCD patients undergoing free tissue transfer and
      reconstruction. METHOD: A literature review was performed in PubMed of 'sickle
      [TiAb] AND plast* adj3 surg*. RESULTS: Sickle cell disease is explained, as is
      the relative peri-operative risk in different genotypes of SCD. Acute and chronic
      manifestations of SCD are described by system, for consideration at pre-operative
      assessment and post-operative review. The evidence surrounding free tissue
      transfer and SCD is discussed and the outcomes in published cases summarised. An
      algorithm for peri-operative multi-disciplinary management is outlined and
      justified. CONCLUSION: Free tissue transfer theoretically carries a high risk of
      a crisis, due not only to long anaesthetic times, but the potential requirement
      for tourniquet use, and the relatively hypoxic state of the transferred tissue.
      This paper outlines a useful, practical algorithm to optimise the safety of free
      tissue transfer in patients with SCD.

PMID- 27866857
TI  - Cognitive impairment in Parkinson's disease.

PMID- 27866859
TI  - Trastuzumab emtansine for HER2-positive breast cancer.

PMID- 27866858
TI  - Clinical variables and biomarkers in prediction of cognitive impairment in
      patients with newly diagnosed Parkinson's disease: a cohort study.
AB  - BACKGROUND: Parkinson's disease is associated with an increased incidence of
      cognitive impairment and dementia. Predicting who is at risk of cognitive decline
      early in the disease course has implications for clinical prognosis and for
      stratification of participants in clinical trials. We assessed the use of
      clinical information and biomarkers as predictive factors for cognitive decline
      in patients with newly diagnosed Parkinson's disease. METHODS: The Parkinson's
      Progression Markers Initiative (PPMI) study is a cohort study in patients with
      newly diagnosed Parkinson's disease. We evaluated cognitive performance (Montreal
      Cognitive Assessment [MoCA] scores), demographic and clinical data, APOE status,
      and biomarkers (CSF and dopamine transporter [DAT] imaging results). Using change
      in MoCA scores over 2 years, MoCA scores at 2 years' follow-up, and a diagnosis
      of cognitive impairment (combined mild cognitive impairment or dementia) at 2
      years as outcome measures, we assessed the predictive values of baseline clinical
      variables and separate or combined additions of APOE status, DAT imaging, and CSF
      biomarkers. We did univariate and multivariate linear analyses with MoCA change
      scores between baseline and 2 years, and with MoCA scores at 2 years as dependent
      variables, using backwards linear regression analysis. Additionally, we
      constructed a prediction model for diagnosis of cognitive impairment using
      logistic regression analysis. FINDINGS: 390 patients with Parkinson's disease
      recruited between July 1, 2010, and May 31, 2013, and for whom data on MoCA
      scores at baseline and 2 years were available. In multivariate analyses, baseline
      age, University of Pennsylvania Smell Inventory Test (UPSIT) scores, CSF amyloid 
      (Abeta42) to t-tau ratio, and APOE status were associated with change in MoCA
      scores over time. Baseline age, MoCA and UPSIT scores, and CSF Abeta42 to t-tau
      ratio were associated with MoCA score at 2 years (using a backwards p-removal
      threshold of 0.1). Accuracy of prediction of cognitive impairment using age alone
      (area under the curve 0.68, 95% CI 0.60-0.76) significantly improved by addition
      of clinical scores (UPSIT, Rapid Eye Movement Sleep Behaviour Disorder Screening
      Questionnaire [RBDSQ], Geriatric Depression Scale, and Movement Disorder Society
      Unified Parkinson's Disease Rating Scale motor scores; 0.76, 0.68-0.83), CSF
      variables (0.74, 0.68-0.81), or DAT imaging results (0.76, 0.68-0.83). In
      combination, the five variables showing the most significant associations with
      cognitive impairment (age, UPSIT, RBDSQ, CSF Abeta42, and caudate uptake on DAT
      imaging) allowed prediction of cognitive impairment at 2 years (0.80, 0.74-0.87;
      p=0.0003 compared to age alone). INTERPRETATION: In newly diagnosed Parkinson's
      disease, the occurrence of cognitive impairment at 2 year follow-up can be
      predicted with good accuracy using a model combining information on age, non
      motor assessments, DAT imaging, and CSF biomarkers. FUNDING: None.

PMID- 27866860
TI  - Hyperprogressive disease with anti-PD-1 and anti-PD-L1.

PMID- 27866861
TI  - Outcomes after transplantation of lungs preserved for more than 12 h: a
      retrospective study.
AB  - BACKGROUND: Ex-vivo lung perfusion (EVLP) can be used to extend overall lung
      preservation time by splitting one long cold ischaemic time into two shorter ones
      and interposing an additional EVLP time. We assessed the outcomes after clinical
      transplantation of lungs with more than 12 h of preservation time. METHODS: For
      this retrospective study, we searched the Toronto Lung Transplant Program
      database for patients who had received at least one lung transplant between Jan
      1, 2006, and April 30, 2015, at a single hospital in Toronto, Canada. We split
      the identified patients into those with a total preservation time of more than 12
      h and those with a total preservation time of less than 12 h to act as the
      control group. Total preservation time was defined as the sum of first cold
      ischaemic time, EVLP time, and second cold ischaemic time. We excluded patients
      if they had received a heart-lung transplant or were younger than 18 years. In
      bilateral lung transplantations, we used the longer preservation time of the two
      lungs for analysis. Lung preservation was done according to present standards of
      care and EVLP was done according to the Toronto EVLP technique. The primary
      outcomes were survival and International Society for Heart and Lung
      Transplantation Primary Graft Dysfunction (PGD) grade at 72 h post
      transplantation. We compared outcomes with our control group using univariable
      and multivariable models. FINDINGS: We identified 906 patients who met
      eligibility criteria and had sufficient data for analysis (<12 h group [n=809];
      mean lung preservation time 400.8 min [SD 121.8] vs >12 h group [n=97]; 875.7 min
      [109.0]). Median hospital and intensive-care unit length of stay were similar
      between the less than 12 h group and the more than 12 h group (hospital stay: 23
      days [16-42] vs 25.5 days [17-50.25], p=0.60; intensive-care unit stay: 4 days [2
      14] vs 4 days [2-16], p=0.53). PGD grade was also not different between the two
      groups at 72 h post-transplantation (p=0.85). There was also no difference in
      survival between the two groups as shown on Kaplan-Meier survival curves
      (p=0.61). Multivariable survival analysis using Cox's model showed increasing
      recipient age to be a significant variable affecting survival. INTERPRETATION:
      Extension of graft preservation time beyond 12 h with EVLP does not negatively
      affect early lung transplantation outcomes. Extension of clinical lung
      preservation times might allow for more transplantations to be done as a result
      of improved facilitation and increased flexibility around timing of lung
      transplantation operations. FUNDING: None.

PMID- 27866863
TI  - IL-2 complex treatment amplifies CD8+ T cell mediated immunity following herpes
      simplex virus-1 infection.
AB  - CD8+ T cells play an important role in controlling numerous virus infections and
      some tumors and therefore several strategies have been adopted to modulate CD8+ T
      cell responses. One such approach includes treatment with IL-2 bound to a
      monoclonal antibody against IL-2 (IL-2 complex) which was shown to enhance CD8+ T
      cell responses and provide protection against some cancers and pathogens. This
      report analyses the value of IL-2 complex therapy to protect against a cutaneous
      virus infection as occurs with herpes simplex virus-1 (HSV-1) infection.
      Treatment with IL-2 complex after infection reduced virus levels and lesion
      severity in a zosteriform model of HSV infection in mice. Furthermore, IL-2
      complex treatment expanded HSV-1-gB epitope-specific CD8+ T cells, IFN-gamma and
      TNF-alpha producing CD8+ T cells as well as cells that produced more than one
      cytokine. In addition, IL-2 complex therapy recipients showed enhanced cytolytic
      activity of CD8+ T cells as shown by increased granzyme B expression and lytic
      granule release. Taken, together, these studies demonstrate that IL-2 complex
      therapy can be useful to boost protection against a cutaneous virus infection.

PMID- 27866864
TI  - Anatomical, histochemical and immunohistochemical characterisation of the cardiac
      outflow tract of the silver arowana, Osteoglossum bicirrhosum (Teleostei:
      Osteoglossiformes).
AB  - The cardiac outflow tract of chondrichthyans and actinopterygians is composed of
      a myocardial conus arteriosus and a non-myocardial bulbus arteriosus. In
      teleosts, the conus has been subjected to a reduction in size over the evolution
      in conjunction with the further development of the bulbus. Most studies on the
      outflow tract of the teleost heart refer to species of modern groups and are
      mainly devoted to the bulbus. Knowledge on the outflow tract of species belonging
      to early teleost groups is scarce. The aim here was to characterise the structure
      of the cardiac outflow tract of the silver arowana, a representative of the
      ancient teleost clade of the Osteoglossomorpha. The material consisted of hearts
      from six juvenile animals. The cardiac outflow tract of the silver arowana is
      composed of a conus, which supports two conal valves, and a bulbus. Both
      components are lined externally by the epicardium and internally by the
      endocardium. The conus is immunoreactive to antibodies against myosin heavy
      chains and is composed of compact myocardium, thus contrasting with the
      ventricle, which has exclusively trabeculated myocardium. The bulbus is
      immunoreactive to antibodies against smooth muscle alpha-actin and mainly
      consists of elastic fibres and smooth muscle cells, both arranged in three
      layers, outer, middle and inner. The most remarkable feature of the bulbus is the
      presence of two prominent longitudinal ridges, dorsal and ventral, at the luminal
      side, which serve to anchor the commissures of the conal valves. This arrangement
      has not been described so far in any fish species. Pigment cells, presumably of
      neural crest origin, are present in the subepicardium of the bulbus and anterior
      part of the ventricle.

PMID- 27866862
TI  - Extraordinary long-term and fluctuating persistence of Ebola virus RNA in semen
      of survivors in Guinea: implications for public health.

PMID- 27866865
TI  - Accelerated Partial Breast Irradiation: Executive summary for the update of an
      ASTRO Evidence-Based Consensus Statement.
AB  - PURPOSE: To update the accelerated partial breast irradiation Consensus Statement
      published in 2009 and provide guidance on use of intraoperative radiation therapy
      (IORT) for partial breast irradiation in early-stage breast cancer, based on
      published evidence complemented by expert opinion. METHODS AND MATERIALS: A
      systematic PubMed search using the same terms as the original Consensus Statement
      yielded 419 articles; 44 articles were selected. The authors synthesized the
      published evidence and, through a series of conference calls and e-mails, reached
      consensus regarding the recommendations. RESULTS: The new recommendations include
      lowering the age in the "suitability group" from 60 to 50 years and in the
      "cautionary group" to 40 years for patients who meet all other elements of
      suitability (Table 1). Patients with low-risk ductal carcinoma in situ, as per
      Radiation Therapy Oncology Group 9804 criteria, were categorized in the
      "suitable" group. The task force agreed to maintain the current criteria based on
      margin status. Recommendations for the use of IORT for breast cancer patients
      include: counseling patients regarding the higher risk of ipsilateral breast
      tumor recurrence with IORT compared with whole breast irradiation; the need for
      prospective monitoring of long-term local control and toxicity with low-energy
      radiograph IORT given limited follow-up; and restriction of IORT to women with
      invasive cancer considered "suitable." CONCLUSION: These recommendations will
      provide updated clinical guidance regarding use of accelerated partial breast
      irradiation for radiation oncologists and other specialists participating in the
      care of breast cancer patients.

PMID- 27866866
TI  - Assessment of oral ivermectin versus shampoo in the treatment of pediculosis
      (head lice infestation) in rural areas of Sine-Saloum, Senegal.
AB  - Reports of treatment failure and the emergence of resistance to topical head lice
      treatments have become increasingly common, driving the need for continued
      development of new therapeutic options for pediculosis. Ivermectin has been
      proposed as a potential alternative for the treatment of pediculosis but has not
      been sufficiently evaluated. In this study, the effectiveness of oral ivermectin
      versus shampoo in the treatment of pediculosis in Senegal was compared. The study
      was conducted in two neighbouring villages of Sine-Saloum, Senegal: Dielmo
      (ivermectin trial group; 201 female participants) and Ndiop (shampoo trial group;
      239 female participants). In the ivermectin group, patients received two doses of
      oral ivermectin (400 ug/kg body weight; Mectizan(r)) 7 days apart. In contrast,
      the shampoo group received a shampoo treatment based on d-phenothrin (0.23%;
      Hegor(r)). At the beginning of the study, 70 (34.8%) of 201 participants in the
      ivermectin group were infested by head lice versus 145 (60.7%) of 239
      participants in the shampoo group. At Day 15 post-treatment, the efficacy of the
      treatment against head lice reached 41/53 (77.4%) in the ivermectin group (53
      patients were tested in this group) versus 42/130 (32.3%) in the shampoo group
      (130 patients were tested in this group) (P <10-7). However, 4 (7.5%) of the 53
      females in the ivermectin group exhibited probable ivermectin treatment failure,
      suggesting the emergence of ivermectin-resistant lice. This study demonstrates
      that oral ivermectin is highly effective for the treatment of pediculosis
      compared with shampoo, but also suggests that ivermectin resistance may emerge
      during treatment.

PMID- 27866867
TI  - Impact of mild patient prosthesis mismatch on quality of life in patients with
      preserved ejection fraction after isolated aortic valve replacement for aortic
      stenosis.
AB  - AIM: To analyze whether PPM affects QOL and functional status in patients after
      isolated AVR for aortic stenosis (AS) with preserved left ventricular ejection
      fraction (LVEF). METHODS: Consecutive patients who underwent AVR in University
      Hospital Center Zagreb for isolated severe symptomatic AS and preserved EF were
      enrolled. Echo data was obtained from complete transthoracic examinations prior
      and after surgery by offline analysis. Patients were divided into two groups
      according to the presence of PPM (effective orifice area (EOA)/body surface area
      (BSA)<0,85cm2/m2). QOL was assessed by telephone interview using Short Form 36
      Item Health Survey (SF-36) along with functional NYHA status estimation. RESULTS:
      A total of 45 pts were included (23 female), and divided in PPM (n=26), and non
      PPM group (n=19). Both groups were similar in pts age, LVEF, AVA/BSA prior
      surgery. After surgery, 57% of pts had PPM categorized as mild PPM. During follow
      up of 2,5years, 3 pts had died and 10 were lost from following. There was no
      difference in NYHA status after surgery between groups (p=0,758). SF36 results
      showed no difference between groups. However, there was a significant improvement
      in Physical functioning (47,50% vs 75,47%,p=0,000) and Role limitation due to
      physical health (41,41% vs 81,25%, p=0,007) scores in the whole study population
      after AVR. Males had significantly better Energy/fatigue (p=0,034), Social
      functioning (p=0,004) and Pain (p=0,017) scores. CONCLUSIONS: Mild to moderate
      PPM showed no clinical relevance. All patients revealed improvement in QOL after
      AVR, while male sex was related to better functioning scores irrespectively of
      PPM.

PMID- 27866870
TI  - Commentary to "Management of undescended testes: European Association of
      Urology/European Society for Paediatric Urology Guidelines".

PMID- 27866869
TI  - Clinical characteristics and outcomes of Yemeni patients with acute heart failure
      aged 50years or younger: Data from Gulf Acute Heart Failure Registry (Gulf CARE).
AB  - AIMS: There is a shortage of data about acute heart failure (AHF) in the young,
      including its underlying causes, clinical presentation and outcomes. We aim to
      describe clinical characteristics, causes and outcomes of AHF in Yemeni patients
      aged 50years or younger. METHODS AND RESULTS: we evaluated Yemeni patients with
      AHF enrolled in Gulf CARE registry. Patients were divided into two groups: young
      patients (<=50years) and older patients (>50years). A total of 1536 patients with
      AHF were enrolled, of whom 635 (41.3%) were 50years old or younger. The mean age
      for this group was 38.8 (+/-9.5) years; and 399 (62.8%) were males. Younger
      patients had a higher prevalence of non-ischemic cardiomyopathy (41% vs 11.1%,
      p<0.001), primary valvular disease (27.9% vs 3.2%, p<0.001), viral myocarditis
      (0.8% vs 0, p<0.001). Ischemic heart disease (61.6% vs 25.5%, p<0.001) and
      hypertensive heart disease (18.3% vs 6.3%, p<0.001) were more frequent in the
      elderly group. Cardiogenic shock was more frequent among younger patients (13.7%
      vs 7.0, p<0.001). In-hospital mortality was higher in patient aged <=50years (12%
      vs 7.6%, p=0.002) while no difference in all-cause mortality was present at
      3months (17.8 vs 14.5, p=0.089) and after 1year (21.9% vs 20.6%, p=0.56).
      CONCLUSION: This analysis of Gulf CARE registry represents the largest report of
      patients admitted with AHF in Yemen. There were differences among cause of HF and
      precipitating factors of AHF among younger and elderly patients. Younger patients
      had higher in-hospital mortality and more severe clinical condition at admission.

PMID- 27866868
TI  - Lack of evidence of lower 30-day all-cause readmission in Medicare beneficiaries
      with heart failure and reduced ejection fraction discharged on spironolactone.
AB  - BACKGROUND: Therapy with evidence-based heart failure (HF) medications has been
      shown to be associated with lower risk of 30-day all-cause readmission in
      patients with HF and reduced ejection fraction (HFrEF). METHODS: We examined the
      association of aldosterone antagonist use with 30-day all-cause readmission in
      this population. Of the 2443 Medicare beneficiaries with HF and left ventricular
      EF <=35% discharged home from 106 Alabama hospitals during 1998-2001, 2060 were
      eligible for spironolactone therapy (serum creatinine <=2.5 for men and <=2mg/dl
      for women, and serum potassium <5mEq/L). After excluding 186 patients already
      receiving spironolactone on admission, the inception cohort consisted of 1874
      patients eligible for a new discharge prescription for spironolactone, of which
      329 received one. Using propensity scores for initiation of spironolactone
      therapy, we assembled a matched cohort of 324 pairs of patients receiving and not
      receiving spironolactone balanced on 34 baseline characteristics (mean age
      72years, 42% women, 33% African American). RESULTS: Thirty-day all-cause
      readmission occurred in 17% and 19% of matched patients receiving and not
      receiving spironolactone, respectively (hazard ratio [HR], 0.92; 95% confidence
      interval [CI], 0.64-1.32; p=0.650). Spironolactone had no association with 30-day
      all-cause mortality (HR, 0.84; 95% CI, 0.38-1.88; p=0.678) or HF readmission (HR,
      0.74; 95% CI, 0.41 1.31; p=0.301). These associations remained unchanged during
      12months of post-discharge follow-up. CONCLUSION: A discharge prescription for
      spironolactone had no association with 30-day all-cause readmission among older,
      hospitalized Medicare beneficiaries with HFrEF eligible for spironolactone
      therapy.

PMID- 27866871
TI  - Endoscopic ultrasound of pancreatic tumors.
AB  - Computed tomography (CT) and endoscopic ultrasound (EUS) are the two most
      effective techniques for the assessment of pancreatic cancers. CT has
      revolutionized the field of tumor imaging in pancreatic cancer and is now a well
      established imaging technique for diagnosis and staging. However, EUS still plays
      an important role in several situations, especially when the diagnosis is
      uncertain or when histopathological confirmation of the lesion is needed.
      Similarly, regarding cystic lesions, magnetic resonance imaging and CT have very
      good performances but are often inadequate because the diagnosis can be difficult
      to establish, while the consequences for the patient are major. New biopsy
      needles, the use of elastography and ultrasonographic contrast agents, and
      confocal laser endomicroscopy can also provide additional and essential
      information to improve diagnosis confidence of pancreatic lesions with EUS.

PMID- 27866872
TI  - Commitment issues: PrEP adherence in injecting drug users.

PMID- 27866873
TI  - Factors associated with the uptake of and adherence to HIV pre-exposure
      prophylaxis in people who have injected drugs: an observational, open-label
      extension of the Bangkok Tenofovir Study.
AB  - BACKGROUND: Results of the randomised, double-blind, placebo-controlled Bangkok
      Tenofovir Study (BTS) showed that taking tenofovir daily as pre-exposure
      prophylaxis (PrEP) can reduce the risk of HIV infection by 49% in people who
      inject drugs. In an extension to the trial, participants were offered 1 year of
      open-label tenofovir. We aimed to examine the demographic characteristics, drug
      use, and risk behaviours associated with participants' uptake of and adherence to
      PrEP. METHODS: In this observational, open-label extension of the BTS
      (NCT00119106), non-pregnant, non-breastfeeding, HIV-negative BTS participants,
      all of whom were current or previous injecting drug users at the time of
      enrolment in the BTS, were offered daily oral tenofovir (300 mg) for 1 year at 17
      Bangkok Metropolitan Administration drug-treatment clinics. Participant
      demographics, drug use, and risk behaviours were assessed at baseline and every 3
      months using an audio computer-assisted self-interview. HIV testing was done
      monthly and serum creatinine was assessed every 3 months. We used logistic
      regression to examine factors associated with the decision to take daily
      tenofovir as PrEP, the decision to return for at least one PrEP follow-up visit,
      and greater than 90% adherence to PrEP. FINDINGS: Between Aug 1, 2013, and Aug
      31, 2014, 1348 (58%) of the 2306 surviving BTS participants returned to the
      clinics, 33 of whom were excluded because they had HIV (n=27) or grade 2-4
      creatinine results (n=6). 798 (61%) of the 1315 eligible participants chose to
      start open-label PrEP and were followed up for a median of 335 days (IQR 0-364).
      339 (42%) participants completed 12 months of follow-up; 220 (28%) did not return
      for any follow-up visits. Participants who were 30 years or older (odds ratio
      [OR] 1.8, 95% CI 1.4-2.2; p<0.0001), injected heroin (OR 1.5, 1.1-2.1; p=0.007),
      or had been in prison (OR 1.7, 1.3-2.1; p<0.0001) during the randomised trial
      were more likely to choose PrEP than were those without these characteristics.
      Participants who reported injecting heroin or being in prison during the 3 months
      before open-label enrolment were more likely to return for at least one open
      label follow-up visit than those who did not report injecting heroin (OR 3.0, 95
      % CI 1.3-7.3; p=0.01) or being in prison (OR 2.3, 1.4-3.7; p=0.0007).
      Participants who injected midazolam or were in prison during open-label follow-up
      were more likely to be greater than 90% adherent than were those who did not
      inject midazolam (OR 2.2, 95% CI 1.2-4.3; p=0.02) or were not in prison (OR 4.7,
      3.1-7.2; p<0.0001). One participant tested positive for HIV, yielding an HIV
      incidence of 2.1 (95% CI 0.05-11.7) per 1000 person-years. No serious adverse
      events related to tenofovir use were reported. INTERPRETATION: More than 60% of
      returning, eligible BTS participants started PrEP, which indicates that a
      substantial proportion of PWID who are knowledgeable about PrEP might be
      interested in taking it. Participants who had injected heroin or been in prison
      were more likely to choose to take PrEP, suggesting that participants based their
      decision to take PrEP, at least in part, on their perceived risk of incident HIV
      infection. FUNDING: US Centers for Disease Control and Prevention and the Bangkok
      Metropolitan Administration.

PMID- 27866874
TI  - PAR1 Scaffolds TGFbetaRII to Downregulate TGF-beta Signaling and Activate ESC
      Differentiation to Endothelial Cells.
AB  - We studied the function of the G-protein-coupled receptor PAR1 in mediating the
      differentiation of mouse embryonic stem cells (mESCs) to endothelial cells (ECs)
      that are capable of inducing neovascularization. We observed that either deletion
      or activation of PAR1 suppressed mouse embryonic stem cell (mESC) differentiation
      to ECs and neovascularization in mice. This was mediated by induction of
      TGFbetaRII/TGFbetaRI interaction, forming an active complex, which in turn
      induced SMAD2 phosphorylation. Inhibition of TGF-beta signaling in PAR1-deficient
      mESCs restored the EC differentiation potential of mESCs. Thus, PAR1 in its
      inactive unligated state functions as a scaffold for TGFbetaRII to downregulate
      TGF-beta signaling, and thereby promote ESC transition to functional ECs. The
      PAR1 scaffold function in ESCs is an essential mechanism for dampening TGF-beta
      signaling and regulating ESC differentiation.

PMID- 27866875
TI  - p53 and p73 Regulate Apoptosis but Not Cell-Cycle Progression in Mouse Embryonic
      Stem Cells upon DNA Damage and Differentiation.
AB  - Embryonic stem cells (ESCs) are fast proliferating cells capable of
      differentiating into all somatic cell types. In somatic cells, it is well
      documented that p53 is rapidly activated upon DNA damage to arrest the cell cycle
      and induce apoptosis. In mouse ESCs, p53 can also be functionally activated, but
      the precise biological consequences are not well characterized. Here, we
      demonstrated that doxorubicin treatment initially led to cell-cycle arrest at
      G2/M in ESCs, followed by the occurrence of massive apoptosis. Neither p53 nor
      its target gene p73 was required for G2/M arrest. Instead, p53 and p73 were fully
      responsible for apoptosis. p53 and p73 were also required for differentiation
      induced apoptosis in mouse ESCs. In addition, doxorubicin treatment induced the
      expression of retinoblastoma protein in a p53-dependent manner. Therefore, both
      p53 and p73 are critical in apoptosis induced by DNA damage and differentiation.

PMID- 27866877
TI  - [Resistant or refractory arterial hypertension?]

PMID- 27866876
TI  - PRDM14 Drives OCT3/4 Recruitment via Active Demethylation in the Transition from
      Primed to Naive Pluripotency.
AB  - Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes
      associated with naive pluripotency are repressed in the transition from inner
      cell mass to epiblast cells, followed by upregulation after PGC specification.
      However, the molecular mechanisms underlying the reactivation of pluripotency
      genes are poorly characterized. Here, we exploited the in vitro differentiation
      of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the
      molecular and epigenetic functions of PR domain-containing 14 (PRDM14). We found
      that Prdm14 overexpression in EpiLCs induced their conversion to ESC-like cells
      even in the absence of leukemia inhibitory factor in adherent culture. This was
      impaired by the loss of Kruppel-like factor 2 and ten-eleven translocation (TET)
      proteins. Furthermore, PRDM14 recruited OCT3/4 to the enhancer regions of naive
      pluripotency genes via TET-base excision repair-mediated demethylation. Our
      results provide evidence that PRDM14 establishes a transcriptional network for
      naive pluripotency via active DNA demethylation.

PMID- 27866878
TI  - [Integrated Management Area of Vascular Risk: A new organisational model for
      global control of risk factors].
AB  - Cardiovascular disease (CVD), is a major cause of morbidity and mortality that
      increases the cost of care. Currently there is a low degree of control of the
      main cardiovascular risk factors, although we have a good therapeutic arsenal. To
      achieve the improvement of this reality, a good coordination and
      multidisciplinary participation are essential. The development of new
      organizational models such as the Integrated Management Area of Vascular Risk can
      facilitate the therapeutic harmonization and unification of the health messages
      offered by different levels of care, based on clinical practice guidelines, in
      order to provide patient-centred integrated care.

PMID- 27866879
TI  - Differences in bite force between dolichofacial and brachyfacial individuals:
      Side of mastication, gender, weight and height.
AB  - PURPOSE: Due to the bite force importance in functionality of the masticatory
      system, this study aimed to characterize it in dolichofacial and brachyfacial
      individuals. METHODS: A sample comprised by 190 patients was divided into two
      groups: 90 severe dolichofacial, and 100 severe brachyfacial individuals
      classified according to the VERT index and the face height ratio (Jarabak
      quotient). Bite force was measured by using an adjusted digital dynamometer and
      proper methodology. RESULTS: The sample met the parametric assumptions and
      presented statistical significance when right and left sides of dolichofacial and
      brachyfacial individuals were compared. However, within the same group, no
      differences between the left and right sides were found. Generally, bite force
      was higher for male, left masticator, age between 41-50 years, weighing over
      100kg and between 1.81 and 1.90m tall. CONCLUSIONS: Based on the results of this
      cross-sectional study, it was possible to conclude that the bite force in severe
      brachyfacial individuals was significantly higher than in severe dolichofacial
      individuals, being influenced by gender, weight and height.

PMID- 27866880
TI  - Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With
      Clostridium difficile Infection.
AB  - BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is a highly effective
      therapy for recurrent Clostridium difficile infection (CDI). However,
      transferring undefined living bacteria entails uncontrollable risks for
      infectious and metabolic or malignant diseases, particularly in immunocompromised
      patients. We investigated whether sterile fecal filtrates (containing bacterial
      debris, proteins, antimicrobial compounds, metabolic products, and
      oligonucleotides/DNA), rather than intact microorganisms, are effective in
      patients with CDI. METHODS: We performed a clinical case series to investigate
      the effects of fecal filtrate transfer (FFT) in 5 patients with symptomatic
      chronic-relapsing CDI at the Department of Internal Medicine I at the University
      Hospital Schleswig-Holstein (Kiel, Germany). Patients were followed up for at
      least 6 months and for up to 33 months. Stool was collected from 5 donors
      selected by the patients, and fully characterized according to FMT standards.
      Stool was sterile-filtered to remove small particles and bacteria; the filtrate
      was transferred to patients in a single administration via nasojejunal tube.
      Fecal samples were collected from patients before and at 1 week and 6 weeks after
      FFT. Microbiome, virome, and proteome profiles of donors and patients were
      compared. RESULTS: In all 5 patients, FFT restored normal stool habits and
      eliminated symptoms of CDI for a minimum period of 6 months. Proteome analyses of
      selected FFT filtrates showed no obvious protein candidates associated with
      therapeutic efficacy. 16S ribosomal RNA gene sequencing detected diverse
      bacterial DNA signatures in the filtrates. Analysis of virus-like particles from
      a filtrate found to reduce symptoms of CDI showed a complex signature of
      bacteriophages. Bacterial phylogeny and virome profile analyses of fecal samples
      from recipients indicated longitudinal changes in microbial and viral community
      structures after FFT. CONCLUSIONS: A preliminary investigation of 5 patients with
      CDI shows that transfer of sterile filtrates from donor stool (FFT), rather than
      fecal microbiota, can be sufficient to restore normal stool habits and eliminate
      symptoms. This finding indicates that bacterial components, metabolites, or
      bacteriophages mediate many of the effects of FMT, and that FFT might be an
      alternative approach, particularly for immunocompromised patients.

PMID- 27866881
TI  - [Failure to patients with appointments in primary care].

PMID- 27866882
TI  - Commentary on "The Endovascular Sealing Device in Combination with Parallel
      Grafts for Treatment of Juxta/Suprarenal Abdominal Aortic Aneurysms: Short-term
      Results of a Novel Alternative".

PMID- 27866883
TI  - Comparison of contraction among three dermal substitutes: Morphological
      differences in scaffolds.
AB  - Various kinds of synthetic dermal substitutes are produced and used in clinical
      application and contribute to wound bed preparation for subsequent skin grafting.
      Although their appearance and outcomes are different, the criteria for the
      selection of proper synthetic dermal substitutes is not well defined yet. In this
      study, we focused on the contraction of dermal substitutes and compared the
      morphological differences in scaffolds. A marked contraction was observed with
      Pelnac(r) compared to Integra(r) and Terudermis(r) in vitro. We also showed that
      the pore size of Pelnac(r) was smaller than that of Integra(r) and Terudermis(r).
      The shape of the pore was oval in Pelnac(r), whereas those in Integra(r) and
      Terudermis(r) were more circular. Differences in the morphological structure may
      have affected the contraction of the synthetic dermal substitutes.

PMID- 27866884
TI  - MicroRNA biomarkers of pancreatic injury in a canine model.
AB  - Pancreas-enriched microRNAs have been experimentally investigated in rodents as
      candidate serum biomarkers of pancreatic injury with several different acute
      pancreatic injury models. In the present study, temporal and magnitude responses
      of exocrine pancreas-enriched miR-216a, miR-216b, and miR-217 and endocrine
      enriched miR-375 and miR-148a were measured by droplet digital PCR in serum in a
      caerulein model of pancreatic injury in the dog. All 5 microRNAs followed a
      similar time course that mirrored the responses of the conventional serum
      pancreatic injury biomarkers, amylase and lipase. Detection was improved through
      the use of assays designed against microRNA isomers (isomirs) identified by
      sequencing. Serum biomarker increases were concordant with histopathology defined
      acinar cell injury. Minimal islet cell changes were noted. The pancreas-enriched
      microRNAs demonstrated similar or greater sensitivity, a larger range of
      response, and a higher correlation to acinar cell injury compared to amylase and
      lipase. Our results further support the translational potential of pancreas
      enriched microRNAs as sensitive biomarkers of acinar cell injury with evidence
      from an additional non-clinical model system.

PMID- 27866885
TI  - Surgical Planning for Flexor Digitorum Longus Tendon Transfers: An Anatomic
      Study.
AB  - Posterior tibial tendon dysfunction is often coupled with various degrees of
      hindfoot valgus and equinus. Preoperative planning is essential to appropriate
      procedure choice and surgical efficiency. The purpose of the present study was to
      assess the anatomy at the harvest site for flexor digitorum longus tendon
      transfer, specifically at the master knot of Henry. Thirty fresh-frozen below-the
      knee cadavers were used for dissection. A standard anatomic approach was
      performed for posterior tibial tendon debridement and flexor digitorum longus
      tendon transfer. The flexor digitorum longus tendon was harvested and measured at
      the master knot of Henry. The present anatomic study evaluated the tendon width
      of the flexor digitorum longus tendon at a common harvest site. Of the 30
      specimens, 20 (67%) measured 5 mm and 10 (33%) measured 4 mm. A 5.0-mm
      interference screw would be acceptable in each specimen and therefore would be
      the safest choice. A 4.0-mm interference screw would be acceptable in only 33% of
      the specimens. Males have a slightly more robust flexor digitorum longus tendon
      than females at the harvest site. This information will assist surgeons in
      preoperative planning during stage II flatfoot correction for posterior tibial
      tendon dysfunction.

PMID- 27866886
TI  - Concomitant Contracture of the Knee and Ankle Joint After Gastrocnemius Muscle
      Rupture: A Case Report.
AB  - Injury of the medial head of the gastrocnemius, also called "tennis leg," is
      known to heal uneventfully in most cases with compression and immobilization
      therapy. Failure to heal or long-term complications, including ongoing pain and
      pes equinus, have been documented in only a limited number of case reports. To
      the best of our knowledge, a severe concomitant contracture of the knee and ankle
      joint as a consequence of a maltreated gastrocnemius muscle rupture has not been
      previously reported in English-language reports. The purpose of the present study
      was to report a serious complication of neglected tennis leg with a review of the
      published data.

PMID- 27866887
TI  - Quality of Early Union After First Metatarsophalangeal Joint Arthrodesis.
AB  - The aim of the present retrospective cohort study was to assess the quality of
      union and the clinical outcomes in patients who had undergone first
      metatarsophalangeal joint (MTPJ) fusion using a dorsal plate and plantar lag
      screw. From March 2011 to December 2012, the clinical and radiographic data of 39
      patients (41 feet) who had undergone first MTPJ fusion using a compressive
      locking plate were retrospectively reviewed. All patients had undergone
      postoperative computed tomography at 6 weeks postoperatively to assess union. The
      average metatarsophalangeal angles improved from 23 degrees  +/- 16 degrees 
      preoperatively to 14 degrees  +/- 5 degrees  postoperatively. The dorsiflexion of
      the hallux at the preoperative assessment averaged 17 degrees  +/- 11 degrees 
      and 23 degrees  +/- 5 degrees  postoperatively. At 6 weeks postoperatively, the
      computed tomography scans demonstrated 3 complete fusions (7.3 %) and 38 partial
      unions (92.7%). Also at 6 weeks, the mean +/- standard deviation joint bridging
      was 54% +/- 14.6%. The forefoot American Orthopaedic Foot and Ankle Society scale
      score had improved significantly from 50 +/- 13 preoperatively to 80 +/- 7 at >1
      year of follow-up (p = .001). Hardware removal was performed in 8 cases because
      of pain in 7 and infection in 1. Revision arthrodesis was required in 2 cases
      because of nonunion. At 6 weeks postoperatively, partial bony joint bridging
      could be observed in most cases after arthrodesis of the first MTPJ with the
      dorsal fusion plate.

PMID- 27866888
TI  - Comparative Analysis of Ciliary Membranes and Ectosomes.
AB  - Primary and motile cilia/flagella function as cellular antennae, receiving
      signals from the environment and subsequently activating signaling pathways that
      are critical for cellular homeostasis and differentiation [1-3]. Recent work with
      the green alga Chlamydomonas and the nematode C. elegans demonstrated that
      ectosomes can be released from the cilium and can mediate the intercellular
      communication [4-9]. To better understand the function of flagellar ectosomes, we
      have compared their protein composition to that of the flagellar membrane from
      which they are derived. Ectosomes released from flagella have a unique protein
      composition, being enriched in a subset of flagellar membrane proteins,
      proteases, proteins from the endosomal sorting complex required for transport
      (ESCRT) [10-12], small GTPases, and ubiquitinated proteins. Live imaging showed
      that an ESCRT-related protein (PDCD6) was enriched in ectosomes released from
      flagella during gamete activation. We devised a sensitive and rapid assay to
      monitor ectosome release using luciferase fused to PDCD6 and a mutated ubiquitin.
      Ectosome release increased when cells underwent flagellar resorption. Knockdown
      of two ESCRT-related proteins, PDCD6 and VPS4, attenuated ectosome release during
      flagellar shortening and shortening was slowed. These data suggest that the ESCRT
      proteins mediate ectosome release and thereby influence flagellar shortening in
      Chlamydomonas. In addition, the prevalence of receptors such as agglutinin and
      ubiquitinated proteins in ciliary ectosomes suggests that they are involved in
      cell signaling and turnover of ciliary proteins.

PMID- 27866890
TI  - Genome Sequence of a 5,310-Year-Old Maize Cob Provides Insights into the Early
      Stages of Maize Domestication.
AB  - The complex evolutionary history of maize (Zea mays L. ssp. mays) has been
      clarified with genomic-level data from modern landraces and wild teosinte grasses
      [1, 2], augmenting archaeological findings that suggest domestication occurred
      between 10,000 and 6,250 years ago in southern Mexico [3, 4]. Maize rapidly
      evolved under human selection, leading to conspicuous phenotypic transformations,
      as well as adaptations to varied environments [5]. Still, many questions about
      the domestication process remain unanswered because modern specimens do not
      represent the full range of past diversity due to abandonment of unproductive
      lineages, genetic drift, on-going natural selection, and recent breeding
      activity. To more fully understand the history and spread of maize, we
      characterized the draft genome of a 5,310-year-old archaeological cob excavated
      in the Tehuacan Valley of Mexico. We compare this ancient sample against a
      reference panel of modern landraces and teosinte grasses using D statistics,
      model-based clustering algorithms, and multidimensional scaling analyses,
      demonstrating the specimen derives from the same source population that gave rise
      to modern maize. We find that 5,310 years ago, maize in the Tehuacan Valley was
      on the whole genetically closer to modern maize than to its wild counterpart.
      However, many genes associated with key domestication traits existed in the
      ancestral state, sharply contrasting with the ubiquity of derived alleles in
      living landraces. These findings suggest much of the evolution during
      domestication may have been gradual and encourage further paleogenomic research
      to address provocative questions about the world's most produced cereal.

PMID- 27866889
TI  - The Mechanism Forming the Cell Surface of Tip-Growing Rooting Cells Is Conserved
      among Land Plants.
AB  - To discover mechanisms that controlled the growth of the rooting system in the
      earliest land plants, we identified genes that control the development of
      rhizoids in the liverwort Marchantia polymorpha. 336,000 T-DNA transformed lines
      were screened for mutants with defects in rhizoid growth, and a de novo genome
      assembly was generated to identify the mutant genes. We report the identification
      of 33 genes required for rhizoid growth, of which 6 had not previously been
      functionally characterized in green plants. We demonstrate that members of the
      same orthogroup are active in cell wall synthesis, cell wall integrity sensing,
      and vesicle trafficking during M. polymorpha rhizoid and Arabidopsis thaliana
      root hair growth. This indicates that the mechanism for constructing the cell
      surface of tip-growing rooting cells is conserved among land plants and was
      active in the earliest land plants that existed sometime more than 470 million
      years ago [1, 2].

PMID- 27866891
TI  - Confidence Is the Bridge between Multi-stage Decisions.
AB  - Demanding tasks often require a series of decisions to reach a goal. Recent
      progress in perceptual decision-making has served to unite decision accuracy,
      speed, and confidence in a common framework of bounded evidence accumulation,
      furnishing a platform for the study of such multi-stage decisions. In many
      instances, the strategy applied to each decision, such as the speed-accuracy
      trade-off, ought to depend on the accuracy of the previous decisions. However, as
      the accuracy of each decision is often unknown to the decision maker, we
      hypothesized that subjects may carry forward a level of confidence in previous
      decisions to affect subsequent decisions. Subjects made two perceptual decisions
      sequentially and were rewarded only if they made both correctly. The speed and
      accuracy of individual decisions were explained by noisy evidence accumulation to
      a terminating bound. We found that subjects adjusted their speed-accuracy setting
      by elevating the termination bound on the second decision in proportion to their
      confidence in the first. The findings reveal a novel role for confidence and a
      degree of flexibility, hitherto unknown, in the brain's ability to rapidly and
      precisely modify the mechanisms that control the termination of a decision.

PMID- 27866893
TI  - Effective Connectivity Reveals Largely Independent Parallel Networks of Face and
      Body Patches.
AB  - The primate brain processes objects in the ventral visual pathway. One object
      category, faces, is processed in a hierarchical network of interconnected areas
      along this pathway. It remains unknown whether such an interconnected network is
      specific for faces or whether there are similar networks for other object
      classes. For example, the primate inferotemporal cortex also contains a set of
      body-selective patches, adjacent to the face-selective patches, but it is not
      known whether these body-selective patches form a similar discretely connected
      network or whether cross-talk exists between the face- and body-processing
      systems. To address these questions, we combined fMRI with electrical
      microstimulation to determine the effective connectivity of fMRI-defined face and
      body patches. We found that microstimulation of face patches caused increased
      fMRI activation throughout the face-processing system; microstimulation of the
      body patches gave similar results restricted to the body-processing system.
      Critically, our results revealed largely segregated connectivity patterns for the
      body and face patches. These results suggest that face and body patches form two
      interconnected hierarchical networks that are largely separated within the monkey
      inferotemporal cortex. Only a restricted number of voxels were activated by
      stimulation of both the body and face patches. The latter regions may be
      important for the integration of face and body information. Our findings are not
      only essential to advance our understanding of the neural circuits that enable
      social cognition, but they also provide further insights into the organizing
      principles of the inferotemporal cortex.

PMID- 27866892
TI  - Tropomyosin and Profilin Cooperate to Promote Formin-Mediated Actin Nucleation
      and Drive Yeast Actin Cable Assembly.
AB  - Tropomyosins comprise a large family of actin-binding proteins with critical
      roles in diverse actin-based processes [1], but our understanding of how they
      mechanistically contribute to actin filament dynamics has been limited. We
      addressed this question in S. cerevisiae, where tropomyosins (Tpm1 and Tpm2),
      profilin (Pfy1), and formins (Bni1 and Bnr1) are required for the assembly of an
      array of actin cables that facilitate polarized vesicle delivery and daughter
      cell growth. Formins drive cable formation by promoting actin nucleation and by
      accelerating actin filament elongation together with profilin [2]. In contrast,
      how tropomyosins contribute mechanistically to cable formation has been unclear,
      but genetic studies demonstrate that Tpm1 plays a more important role than Tpm2
      [3, 4]. Here, we found that loss of TPM1 in strains lacking BNR1, but not BNI1,
      leads to severe defects in cable formation, polarized secretion, and cell growth,
      suggesting that TPM1 function is required for proper Bni1-mediated cable
      assembly. Furthermore, in vitro total internal reflection fluorescence (TIRF)
      microscopy demonstrated that Tpm1 strongly enhances Bni1-mediated, but not Bnr1
      mediated, actin nucleation without affecting filament elongation rate, whereas
      Tpm2 has no effects on Bni1 or Bnr1. Tpm1 stimulation of Bni1-mediated nucleation
      also requires profilin and its interactions with both G-actin and formins.
      Together, these results demonstrate that yeast Tpm1 works in concert with
      profilin to promote formin-dependent nucleation of actin cables, thus expanding
      our understanding of how specific tropomyosin isoforms influence actin dynamics.

PMID- 27866894
TI  - SYP73 Anchors the ER to the Actin Cytoskeleton for Maintenance of ER Integrity
      and Streaming in Arabidopsis.
AB  - The endoplasmic reticulum (ER) is an essential organelle that spreads throughout
      the cytoplasm as one interconnected network of narrow tubules and dilated
      cisternae that enclose a single lumen. The ER network undergoes extensive
      remodeling, which critically depends on membrane-cytoskeleton interactions [1].
      In plants, the ER is also highly mobile, and its streaming contributes
      significantly to the movement of other organelles [2, 3]. The remodeling and
      motility of the plant ER rely mainly on actin [4] and to a minor extent on
      microtubules [5]. Although a three-way interaction between the ER, cytosolic
      myosin-XI, and F-actin mediates the plant ER streaming [6], the mechanisms
      underlying stable interaction of the ER membrane with actin are unknown. Early
      electron microscopy studies suggested a direct attachment of the plant ER with
      actin filaments [7, 8], but it is plausible that yet-unknown proteins facilitate
      anchoring of the ER membrane with the cytoskeleton. We demonstrate here that
      SYP73, a member of the plant Syp7 subgroup of SNARE proteins [9] containing actin
      binding domains, is a novel ER membrane-associated actin-binding protein. We show
      that overexpression of SYP73 causes a striking rearrangement of the ER over actin
      and that, similar to mutations of myosin-XI [4, 10, 11], loss of SYP73 reduces ER
      streaming and affects overall ER network morphology and plant growth. We propose
      a model for plant ER remodeling whereby the dynamic rearrangement and streaming
      of the ER network depend on the propelling action of myosin-XI over actin coupled
      with a SYP73-mediated bridging, which dynamically anchors the ER membrane with
      actin filaments.

PMID- 27866895
TI  - Empty Niches after Extinctions Increase Population Sizes of Modern Corals.
AB  - Large environmental fluctuations often cause mass extinctions, extirpating
      species and transforming communities [1, 2]. While the effects on community
      structure are evident in the fossil record, demographic consequences for
      populations of individual species are harder to evaluate because fossils reveal
      relative, but not absolute, abundances. However, genomic analyses of living
      species that have survived a mass extinction event offer the potential for
      understanding the demographic effects of such environmental fluctuations on
      extant species. Here, we show how environmental variation since the Pliocene has
      shaped demographic changes in extant corals of the genus Orbicella, major extant
      reef builders in the Caribbean that today are endangered. We use genomic
      approaches to estimate previously unknown current and past population sizes over
      the last 3 million years. Populations of all three Orbicella declined around 2-1
      million years ago, coincident with the extinction of at least 50% of Caribbean
      coral species. The estimated changes in population size are consistent across the
      three species despite their ecological differences. Subsequently, two shallow
      water specialists expanded their population sizes at least 2-fold, over a time
      that overlaps with the disappearance of their sister competitor species O. nancyi
      (the organ-pipe Orbicella). Our study suggests that populations of Orbicella
      species are capable of rebounding from reductions in population size under
      suitable conditions and that the effective population size of modern corals
      provides rich standing genetic variation for corals to adapt to climate change.
      For conservation genetics, our study suggests the need to evaluate genetic
      variation under appropriate demographic models.

PMID- 27866896
TI  - Performance of the irregular surface compensator compared with four-field box and
      intensity modulated radiation therapy for gynecologic cancer.
AB  - PURPOSE: A retrospective planning study was undertaken to evaluate the dosimetric
      advantages of the irregular surface compensator (ISC) technique, a forward
      planning technique with electronic compensation algorithm available on Varian
      Eclipse treatment planning system. This was extensively compared to the
      conventional four-field box (4FB) and intensity modulated radiation therapy using
      5 fields (IMRT5F) on gynecologic cancer patients. METHODS: Twenty-two patients
      were enrolled. The prescribed dose was 50.4Gy in 28 fractions to the primary
      target including pelvic lymph nodes. 4FB treatment plans were generated, then
      fluence of anterior and posterior fields were modified to generate ISC plans.
      IMRT5F were inversely optimized with equally spaced five coplanar fields. Dose
      volume parameters were evaluated for the comparison of three planning techniques.
      The MU and delivery time were also estimated. RESULTS: In terms of target
      coverage, the conformity and homogeneity index of ISC (1.67 and 1.03,
      respectively) were superior to those of 4FB (2.43 and 1.06, respectively) but
      slightly inferior to those of IMRT5F (1.10 and 1.02, respectively). ISC also
      illustrated an overall improvement in normal organ saving. Compared to 4FB, the
      mean dose of the rectum was reduced by about 4.0-5.0Gy with ISC and IMRT5F. The
      volume receiving large doses was reduced for bladder with statistical
      significance with ISC and more with IMRT5F relative to 4FB. The mean number of MU
      per fraction were 200.86 (4FB), 446.09 (ISC) and 895.59 (IMRT5F). CONCLUSION: The
      ISC technique has the superior target coverage and healthy tissue sparing in
      comparison with conventional 4FB and comparable normal organ saving compared to
      IMRT5F. The ISC can be an available option for gynecologic radiotherapy.

PMID- 27866897
TI  - Dosimetric and bremsstrahlung performance of a single convergent beam for
      teletherapy device.
AB  - The present work investigates preliminary feasibility and characteristics of a
      new type of radiation therapy modality based on a single convergent beam of
      photons. The proposal consists of the design of a device capable of generating
      convergent X-ray beams useful for radiotherapy. The main goal is to achieve high
      concentrated dose delivery. The first step is an analytical approach in order to
      characterize the dosimetric performance of the hypothetical convergent photon
      beam. Then, the validated FLUKA Monte Carlo main code is used to perform complete
      radiation transport to account also for scattering effects. The proposed method
      for producing convergent X-rays is mainly based on the bremsstrahlung effect.
      Hence the operating principle of the proposed device is described in terms of
      bremsstrahlung production. The work is mainly devoted characterizing the effect
      on the bremsstrahlung yield due to accessories present in the device, like anode
      material and geometry, filtration and collimation systems among others. The
      results obtained for in-depth dose distributions, by means of analytical and
      stochastic approaches, confirm the presence of a high dose concentration around
      the irradiated target, as expected. Moreover, it is shown how this spot of high
      dose concentration depends upon the relevant physical properties of the produced
      convergent photon beam. In summary, the proposed design for producing single
      convergent X-rays attained satisfactory performance for achieving high dose
      concentration around small targets depending on beam spot size that may be used
      for some applications in radiotherapy, like radiosurgery.

PMID- 27866899
TI  - Potential of compact Compton sources in the medical field.
AB  - The exceptional improvement of high power lasers and optical cavity finesses in
      the last fifteen years allows today the development of X-ray sources based on
      inverse Compton scattering. These compact sources will provide high intensity
      beams, with a tunable energy in the range 20-100keV, that can be used in several
      application including material sciences, structural biology, cultural heritage
      research and preservation and medical or biomedical preclinical and clinical
      research. The access to these devices will be easier. Methods currently used only
      in synchrotron facilities will be available in dedicated work environment such as
      hospitals, laboratories or museums. Several machines are in design or
      construction phase, and aim at producing 1012-1014ph/s. The ThomX machine is the
      most advanced project and has the potential to be used as the radiation source
      for biomedical searches, clinical imaging techniques or radiotherapy programs.

PMID- 27866898
TI  - Optimizing dose enhancement with Ta2O5 nanoparticles for synchrotron microbeam
      activated radiation therapy.
AB  - Microbeam Radiation Therapy (MRT) exploits tumour selectivity and normal tissue
      sparing with spatially fractionated kilovoltage X-ray microbeams through the dose
      volume effect. Experimental measurements with Ta2O5 nanoparticles (NPs) in 9L
      gliosarcoma treated with MRT at the Australian Synchrotron, increased the
      treatment efficiency. Ta2O5 NPs were observed to form shells around cell nuclei
      which may be the reason for their efficiency in MRT. In this article, our
      experimental observation of NP shell formation is the basis of a Geant4 radiation
      transport study to characterise dose enhancement by Ta2O5 NPs in MRT. Our study
      showed that NP shells enhance the physical dose depending microbeam energy and
      their location relative to a single microbeam. For monochromatic microbeam
      energies below ~70keV, NP shells show highly localised dose enhancement due to
      the short range of associated secondary electrons. Low microbeam energies
      indicate better targeted treatment by allowing higher microbeam doses to be
      administered to tumours and better exploit the spatial fractionation related
      selectivity observed with MRT. For microbeam energies above ~100keV, NP shells
      extend the physical dose enhancement due to longer-range secondary electrons.
      Again, with NPs selectively internalised, the local effectiveness of MRT is
      expected to increase in the tumour. Dose enhancement produced by the shell
      aggregate varied more significantly in the cell population, depending on its
      location, when compared to a homogeneous NP distribution. These combined
      simulation and experimental data provide first evidence for optimising MRT
      through the incorporation of newly observed Ta2O5 NP distributions within 9L
      cancer cells.

PMID- 27866902
TI  - The atypical antipsychotic olanzapine disturbs depotentiation by modulating
      mAChRs and impairs reversal learning.
AB  - Antipsychotic medication is an essential component for treating schizophrenia,
      which is a serious mental disorder that affects approximately 1% of the global
      population. Olanzapine (Olz), one of the most frequently prescribed atypical
      antipsychotics, is generally considered a first-line drug for treating
      schizophrenia. In contrast to psychotic symptoms, the effects of Olz on cognitive
      symptoms of schizophrenia are still unclear. In addition, the mechanisms by which
      Olz affects the neural circuits associated with cognitive function are unknown.
      Here we show that Olz interrupts depotentiation (reversal of long-term
      potentiation) without disturbing de novo LTP (long-term potentiation) and LTD
      (long-term depression). At hippocampal SC-CA1 synapses, inhibition of NMDARs (N
      methyl-d-aspartate receptors), mGluRs (metabotropic glutamate receptors), or
      mAChRs (muscarinic acetylcholine receptors) disrupted depotentiation. In
      addition, co-activation of NMDARs, mGluRs, and mAChRs reversed stably expressed
      LTP. Olz inhibits the activation of mAChRs, which amplifies glutamate signaling
      through enhanced NMDAR opening and Gq (Gq class of G protein)-mediated signal
      transduction. Behaviorally, Olz impairs spatial reversal learning of mice in the
      Morris water maze test. Our results uncover a novel mechanism underpinning the
      cognitive modulation of Olz and show that the anticholinergic property of Olz
      affects glutamate signaling and synaptic plasticity.

PMID- 27866900
TI  - A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-Induced
      Activation.
AB  - RIG-I detects double-stranded RNA (dsRNA) to trigger antiviral cytokine
      production. Protein deamidation is emerging as a post-translational modification
      that chiefly regulates protein function. We report here that UL37 of herpes
      simplex virus 1 (HSV-1) is a protein deamidase that targets RIG-I to block RNA
      induced activation. Mass spectrometry analysis identified two asparagine residues
      in the helicase 2i domain of RIG-I that were deamidated upon UL37 expression or
      HSV-1 infection. Deamidation rendered RIG-I unable to sense viral dsRNA, thus
      blocking its ability to trigger antiviral immune responses and restrict viral
      replication. Purified full-length UL37 and its carboxyl-terminal fragment were
      sufficient to deamidate RIG-I in vitro. Uncoupling RIG-I deamidation from HSV-1
      infection, by engineering deamidation-resistant RIG-I or introducing deamidase
      deficient UL37 into the HSV-1 genome, restored RIG-I activation and antiviral
      immune signaling. Our work identifies a viral deamidase and extends the paradigm
      of deamidation-mediated suppression of innate immunity by microbial pathogens.

PMID- 27866903
TI  - Emerging concepts in T follicular helper cell responses to malaria.
AB  - Antibody responses to malaria and candidate malaria vaccines are short-lived in
      children, leaving them susceptible to repeated malaria episodes. Because T
      follicular helper (TFH) cells provide critical help to B cells to generate long
      lived antibody responses, they have become the focus of recent studies of
      Plasmodium-infected mice and humans. The emerging data converge on common themes,
      namely, that malaria-induced TH1 cytokines are associated with the activation of
      (i) T-like memory TFH cells with impaired B cell helper function, and (ii) pre
      TFH cells that acquire Th1-like features (T-bet expression, IFN-gamma
      production), which impede their differentiation into fully functional TFH cells,
      thus resulting in germinal center dysfunction and suboptimal antibody responses.
      Deeper knowledge of TFH cells in malaria could illuminate strategies to improve
      vaccines through modulating TFH cell responses. This review summarizes emerging
      concepts in TFH cell responses to malaria.

PMID- 27866901
TI  - Histones Are Rapidly Loaded onto Unintegrated Retroviral DNAs Soon after Nuclear
      Entry.
AB  - Chromosomal structure of nuclear DNA is usually maintained by insertion of
      nucleosomes into preexisting chromatin, both on newly synthesized DNA at
      replication forks and at sites of DNA damage. But during retrovirus infection, a
      histone-free DNA copy of the viral genome is synthesized that must be loaded with
      nucleosomes de novo. Here, we show that core histones are rapidly loaded onto
      unintegrated Moloney murine leukemia virus DNAs. Loading of nucleosomes requires
      nuclear entry, but does not require viral DNA integration. The histones
      associated with unintegrated DNAs become marked by covalent modifications, with a
      delay relative to the time of core histone loading. Expression from unintegrated
      DNA can be enhanced by modulation of the histone-modifying machinery. The data
      show that histone loading onto unintegrated DNAs occurs very rapidly after
      nuclear entry and does not require prior establishment of an integrated provirus.

PMID- 27866904
TI  - Assessment of the national schistosomiasis control program in a typical region
      along the Yangtze River, China.
AB  - Schistosomiasis remains a major public health problem in eastern China,
      particularly along the Yangtze River Basin. The latest national schistosomiasis
      control program (NSCP) was implemented in 2005 with the main goal of reducing the
      rate of infection to less than 5% by 2008 and 1% by 2015. To assess the progress,
      we applied a Bayesian spatio-temporal model to describe dynamics of
      schistosomiasis in Guichi, Anhui Province, China, using annual parasitological
      and environmental data collected within 41 sample villages for the period 2005
      2011. Predictive maps of schistosomiasis showed that the disease prevalence
      remains constant and low. Results of uncertainty analysis, in the form of
      probability contour maps (PCMs), indicated that the first goal of "infection rate
      less than 5% by 2008" was fully achieved in the study area. More longitudinal
      data for schistosomiasis are needed for the assessment of the second goal of
      "infection rate less than 1% by 2015". Compared with the traditional way of
      mapping uncertainty (e.g., variance or mean-square error), our PCMs provide more
      realistic information for schistosomiasis control.

PMID- 27866905
TI  - KirrelL, a member of the Ig-domain superfamily of adhesion proteins, is essential
      for fusion of primary mesenchyme cells in the sea urchin embryo.
AB  - In the sea urchin embryo, primary mesenchyme cells (PMCs) adhere to one another
      and fuse via filopodia, forming cable-like structures within which skeletal rods
      are deposited. Although this process was first described more than a century ago,
      molecules that participate in PMC adhesion and fusion have not been identified.
      Here we show that KirrelL, a PMC-specific, Ig domain-containing transmembrane
      protein, is essential for PMC fusion, probably by mediating filopodial adhesions
      that are a pre-requisite for subsequent membrane fusion. We show that KirrelL is
      not required for PMC specification, migration, or for direct filopodial contacts
      between PMCs. In the absence of KirrelL, however, filopodial contacts do not
      result in fusion. kirrelL is a member of a family of closely related, intronless
      genes that likely arose through an echinoid-specific gene expansion, possibly via
      retrotransposition. Our findings are significant in that they establish a direct
      linkage between the transcriptional network deployed in the PMC lineage and an
      effector molecule required for a critically important PMC morphogenetic process.
      In addition, our results point to a conserved role for Ig domain-containing
      adhesion proteins in facilitating cell fusion in both muscle and non-muscle cell
      lineages during animal development.

PMID- 27866906
TI  - Successful closure of a cryotherapy-induced bleeding jejunal perforation with the
      over-the-scope clip system.

PMID- 27866907
TI  - Radiofrequency ablation for intraductal extension of ampullary neoplasms.
AB  - BACKGROUND AND AIMS: Extension of ampullary adenomas into the common bile duct
      (CBD) or pancreatic duct (PD) may be difficult to treat endoscopically. We
      evaluated the feasibility, safety, and efficacy of endoscopic radiofrequency
      ablation (RFA) in the management of ampullary neoplasms with intraductal
      extension. METHODS: This was a multicenter, retrospective analysis of all
      patients with intraductal extension of ampullary neoplasms treated with
      endoscopic RFA between February 2012 and June 2015. Treatment success was defined
      as the absence of detectable intraductal polyps by ductography, visual
      inspection, and biopsy sampling. RESULTS: Fourteen patients with adenoma
      extension into the CBD (13 +/- 7 mm, n = 14) and PD (7 +/- 2 mm, n = 3) underwent
      a median of 1 RFA sessions (range, 1-5). Additional modalities (thermal probes,
      argon plasma coagulation, and/or photodynamic therapy) were also used in 7
      patients, and prophylactic stents were routinely placed. Thirteen assessable
      patients underwent a median of 2 surveillance ERCPs after completion of treatment
      over a median follow-up of 16 months (range, 5-46), with intraductal biopsy
      specimens showing no neoplasm in 12 patients at the conclusion of endoscopic
      treatment. Treatment success was achieved in 92%, including 100% of those treated
      with RFA alone. Adverse events occurred in 43% and included ductal strictures (5
      patients) and retroduodenal abscess (1 patient), all of which were successfully
      treated endoscopically. CONCLUSIONS: Endoscopic RFA, alone or in combination with
      other modalities, may effectively treat intraductal extension of ampullary
      neoplasms. Ductal strictures were common after RFA but responded to endoscopic
      stent therapy. RFA may be appropriate in selected patients, particularly when the
      main treatment alternative is pancreaticoduodenectomy.

PMID- 27866908
TI  - Biosynthetic Pathway Connects Cryptic Ribosomally Synthesized Posttranslationally
      Modified Peptide Genes with Pyrroloquinoline Alkaloids.
AB  - In an era where natural product biosynthetic gene clusters can be rapidly
      identified from sequenced genomes, it is unusual for the biosynthesis of an
      entire natural product class to remain unknown. Yet, the genetic determinates for
      pyrroloquinoline alkaloid biosynthesis have remained obscure despite their
      abundance and deceptive structural simplicity. In this work, we have identified
      the biosynthetic gene cluster for ammosamides A-C, pyrroloquinoline alkaloids
      from Streptomyces sp. CNR-698. Through direct cloning, heterologous expression
      and gene deletions we have validated the ammosamide biosynthetic gene cluster and
      demonstrated that these seemingly simple molecules are derived from a
      surprisingly complex set of biosynthetic genes that are also found in the
      biosynthesis of lymphostin, a structurally related pyrroloquinoline alkaloid from
      Salinispora and Streptomyces. Our results implicate a conserved set of genes
      driving pyrroloquinoline biosynthesis that consist of genes frequently associated
      with ribosomal peptide natural product biosynthesis, and whose exact biochemical
      role remains enigmatic.

PMID- 27866909
TI  - Unsaturated Fatty Acid Synthesis in the Gastric Pathogen Helicobacter pylori
      Proceeds via a Backtracking Mechanism.
AB  - Helicobacter pylori is a Gram-negative bacterium that inhabits the upper
      gastrointestinal tract in humans, and the presence of this pathogen in the gut
      microbiome increases the risk of peptic ulcers and stomach cancer. H. pylori
      depends on unsaturated fatty acid (UFA) biosynthesis for maintaining membrane
      structure and function. Although some of the H. pylori enzymes involved in UFA
      biosynthesis are functionally homologous with the enzymes found in Escherichia
      coli, we show here that an enzyme HP0773, now annotated as FabX, uses an
      unprecedented backtracking mechanism to not only dehydrogenate decanoyl-acyl
      carrier protein (ACP) in a reaction that parallels that of acyl-CoA
      dehydrogenase, the first enzyme of the fatty acid beta-oxidation cycle, but also
      isomerizes trans-2-decenoyl-ACP to cis-3-decenoyl-ACP, the key UFA synthetic
      intermediate. Thus, FabX reverses the normal fatty acid synthesis cycle in H.
      pylori at the C10 stage. Overall, this unusual FabX activity may offer a broader
      explanation for how many bacteria that lack the canonical pathway enzymes produce
      UFA-containing phospholipids.

PMID- 27866911
TI  - Structural Insight into the Enzymatic Formation of Bacterial Stilbene.
AB  - In contrast to stilbene biosynthesis by type III polyketide synthase in plants,
      in bacteria stilbene is produced by the collaboration of two enzymes in
      Photorhabdus luminescens: the unusual beta-ketosynthase StlD catalyzes the
      condensation of the beta-ketoacyl starter with an alpha,beta-unsaturated-acyl
      substrate (two C-C bond-forming reactions) to produce
      isopropylstyrylcyclohexanedione, which is subsequently converted to stilbene by
      the aromatase StlC. Here we report the in vitro characterizations of StlD and
      StlC, and the X-ray crystal structures of StlD. Interestingly, structure-based
      mutagenesis demonstrated that His302, within the conserved Cys-His-Asn triad, is
      not essential for the enzyme reaction, while Glu154 functions as a base-catalyst
      to activate the beta-ketoacyl intermediate bound to the catalytic Cys126. The
      structures also revealed the presence of a putative nucleophilic water molecule
      activated by hydrogen bond networks with Glu154 and Ser340, suggesting that StlD
      employs novel catalytic machinery for the condensation of two acyl substrates to
      produce the cyclohexanedione scaffold.

PMID- 27866910
TI  - Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific
      Secondary Targets.
AB  - Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a promising class of
      targeted cancer drugs, but their individual target profiles beyond the PARP
      family, which could result in differential clinical use or toxicity, are unknown.
      Using an unbiased, mass spectrometry-based chemical proteomics approach, we
      generated a comparative proteome-wide target map of the four clinical PARPi,
      olaparib, veliparib, niraparib, and rucaparib. PARPi as a class displayed high
      target selectivity. However, in addition to the canonical targets PARP1, PARP2,
      and several of their binding partners, we also identified hexose-6-phosphate
      dehydrogenase (H6PD) and deoxycytidine kinase (DCK) as previously unrecognized
      targets of rucaparib and niraparib, respectively. Subsequent functional
      validation suggested that inhibition of DCK by niraparib could have detrimental
      effects when combined with nucleoside analog pro-drugs. H6PD silencing can cause
      apoptosis and further sensitize cells to PARPi, suggesting that H6PD may be, in
      addition to its established role in metabolic disorders, a new anticancer target.

PMID- 27866912
TI  - Investigation of candidate genes for osteoarthritis based on gene expression
      profiles.
AB  - OBJECTIVE: To explore the mechanism of osteoarthritis (OA) and provide valid
      biological information for further investigation. METHODS: Gene expression
      profile of GSE46750 was downloaded from Gene Expression Omnibus database. The
      Linear Models for Microarray Data (limma) package (Bioconductor project,
      http://www.bioconductor.org/packages/release/bioc/html/limma.html) was used to
      identify differentially expressed genes (DEGs) in inflamed OA samples. Gene
      Ontology function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathways enrichment analysis of DEGs were performed based on Database for
      Annotation, Visualization and Integrated Discovery data, and protein-protein
      interaction (PPI) network was constructed based on the Search Tool for the
      Retrieval of Interacting Genes/Proteins database. Regulatory network was screened
      based on Encyclopedia of DNA Elements. Molecular Complex Detection was used for
      sub-network screening. Two sub-networks with highest node degree were integrated
      with transcriptional regulatory network and KEGG functional enrichment analysis
      was processed for 2 modules. RESULTS: In total, 401 up- and 196 down-regulated
      DEGs were obtained. Up-regulated DEGs were involved in inflammatory response,
      while down-regulated DEGs were involved in cell cycle. PPI network with 2392
      protein interactions was constructed. Moreover, 10 genes including Interleukin 6
      (IL6) and Aurora B kinase (AURKB) were found to be outstanding in PPI network.
      There are 214 up- and 8 down-regulated transcription factor (TF)-target pairs in
      the TF regulatory network. Module 1 had TFs including SPI1, PRDM1, and FOS, while
      module 2 contained FOSL1. The nodes in module 1 were enriched in chemokine
      signaling pathway, while the nodes in module 2 were mainly enriched in cell
      cycle. CONCLUSION: The screened DEGs including IL6, AGT, and AURKB might be
      potential biomarkers for gene therapy for OA by being regulated by TFs such as
      FOS and SPI1, and participating in the cell cycle and cytokine-cytokine receptor
      interaction pathway.

PMID- 27866913
TI  - Minimally invasive plate osteosynthesis with PHILOS plate for proximal humerus
      fractures.
AB  - OBJECTIVES: The aim of the present study was to evaluate results, including
      clinical and radiological outcomes and number of complications, following
      minimally invasive plate osteosynthesis (MIPO) of proximal humerus fractures,
      using the PHILOS(r) proximal humerus internal locking system (Synthes Holding AG,
      Solothurn, Switzerland). METHODS: Retrospectively evaluated were 31 patients
      treated with MIPO (12 male, 19 female; average age: 58.4 years). Four patients
      had 2-part fractures, 14 patients had 3-part fractures, and 13 patients had 4
      part fractures, according to Neer classification. Healing, complications, and
      head-shaft angle (HSA) were radiographically evaluated. Clinical outcomes were
      assessed at 1-year follow-up with Constant score. RESULTS: Average Constant
      scores for fractured and normal shoulders were 73.2 +/- 10.9 and 84.8 +/- 5.1,
      respectively. Varus progression, fracture type, and age had no significant effect
      on functional outcome. Average postoperative and follow-up HSA's were 130.80 +/-
      7.70 and 128.80 +/- 10.00, respectively. Significant varus progression was
      observed during follow-up (p = 0.01). Varus progression was more prominent in
      patients with postoperative HSA < 130 degrees  (p < 0.001). Inferomedial calcar
      screw usage, fracture type, and age had no significant effect on varus
      progression. Complications included 2 implant failures, 1 case of avascular
      necrosis (AVN), 1 primary screw cut-out, 1 axillary nerve injury, and 1 radial
      nerve injury (22.6% overall). CONCLUSION: MIPO is a safe and effective option for
      the treatment of proximal humerus fractures, with good functional recovery and
      fewer complications, which are typically technique dependent. Reduction may be
      difficult, resulting in varus progression. Another disadvantage is risk of
      axillary nerve injury. Careful surgical technique and correct implant selection
      is important in the prevention of nerve injury. LEVEL OF EVIDENCE: Level IV,
      Therapeutic study.

PMID- 27866914
TI  - Short Form Health Survey version-2.0 Turkish (SF-36v2) is an efficient outcome
      parameter in musculoskeletal research.
AB  - OBJECTIVE: Although the Short Form Health Survey version-2.0 (SF-36v2) is widely
      used since 2000, the researchers and clinicians in Turkey have been still using
      the original version. However, the original version includes many deficiencies
      and the SF-36v2 was introduced aiming to correct these deficiencies. The purpose
      of this study is to indicate differences between SF-36 and SF-36v2 and the
      present cross cultural adaptation, reliability and validity of the SF-36v2.
      PATIENTS AND METHODS: The SF-36v2 was cross culturally adapted to Turkish and the
      measurement properties of the Turkish version of the SF-36v2 were tested in 50
      patients (19 males; mean +/- SD age: 36.9 +/- 14.6 years; range: 16-65 years,
      BMI; 24.1 +/- 4.6) with a variety of musculoskeletal pathologies. Intraclass
      correlation coefficients (ICC) were used to estimate the test-retest reliability.
      Construct validity was analyzed with SF-36v2 and EuroQol Group (EQ-5D). The
      distribution of ceiling and floor effects was determined. RESULTS: During the
      cross-cultural adaptation process many changes were made. The Turkish SF-36v2
      subscales showed excellent test-retest reliability which was ranged 0.80 to 0.95.
      The highest correlation was found between SF-36v2-PCS and SF-36v2-PF (r = 0.75),
      the lowest correlation was found between SF-36v2-PCS and SF-36v2-MH (r = 0.05).
      The correlations between EQ-5D and SF-36v2 subscales ranged from 0.10 (SF-36v2 
      VT) to 0.46 (SF-36v2 -RE). We observed no ceiling and floor effects. CONCLUSION:
      The cultural adaptation of the SF-36v2 was successful. The SF-36v2 has sufficient
      reliability and validity to measure a variety of musculoskeletal pathologies for
      Turkish-speaking individuals.

PMID- 27866915
TI  - Trends in Transcranial Doppler Monitoring in Aneurysmal Subarachnoid Hemorrhage:
      A 10-Year Analysis of the Nationwide Inpatient Sample.
AB  - BACKGROUND: Transcranial Doppler (TCD) is endorsed by national guidelines for use
      in aneurysmal subarachnoid hemorrhage (aSAH) for surveillance of cerebral
      vasospasm (CV). However, nationwide data on utilization of TCD for CV detection
      and monitoring in aSAH are lacking. METHODS: Analysis of nationwide trends in TCD
      prevalence was performed using Nationwide Inpatient Sample (NIS) data from 2002
      to 2011. Raw counts were converted into weighted counts, which were used to
      generate national estimates. Teaching hospitals were examined separately for TCD
      utilization rates. All analyses accounted for the complex sampling design and
      sample discharge weights of the NIS, following Healthcare Cost and Utilization
      Project-NIS recommendations. The objective was to estimate the proportion of
      patients with aSAH receiving TCD monitoring using the NIS. RESULTS: Between 2002
      and 2011, a total of 256,089 patients were discharged with a diagnosis of aSAH,
      of which 3850 underwent TCD monitoring. aSAH accounted for an average of 67.1
      discharges per 100,000 annually (95% confidence interval [CI] 61.3-72.8). Of
      these, 1.5% (95% CI 0.4-2.6) underwent TCD examination. In teaching hospitals,
      aSAH accounted for an average of 108.5 discharges per 100,000 biennially (95% CI,
      96.2-120.8), of which 2% (95% CI 1.0-4.0) underwent TCD examination. TCD
      utilization increased from <1% during the 2002-2005 period to >=1.5% during the
      2006-2011 period (odds ratio 2.3, 95% CI 1.0-5.7), an increase also seen in
      teaching hospitals. CONCLUSIONS: TCD is underused nationally in the care of aSAH.
      Whereas the prevalence of TCD is low in teaching hospitals, it is nearly
      nonexistent in nonteaching hospitals.

PMID- 27866916
TI  - Blood coagulation in immunothrombosis-At the frontline of intravascular immunity.
AB  - While hemostasis is the physiological process that prevents blood loss after
      vessel injury, thrombosis is often portrayed as a pathologic event involving
      blood coagulation and platelet aggregation eventually leading to vascular
      occlusion and tissue damage. However, recent work suggests that thrombosis can
      also be a physiological process, termed immunothrombosis, initiated by the innate
      immune system providing a first line of defense to locally control infection.
      Fibrin forms the structural basis of immunothrombotic clots and its assembly
      involves the concerted action of coagulation factors, platelets and leukocytes.
      Here, we summarize the cellular and molecular events that initiate fibrin
      formation during the innate immune response and discuss how aberrant activation
      of these pathways fosters pathologies associated with thrombosis, including
      disseminated intravascular coagulation and atherothrombosis.

PMID- 27866917
TI  - PRKAG3 polymorphisms associated with sporadic Wolff-Parkinson-White syndrome
      among a Taiwanese population.
AB  - BACKGROUND: The aim of this study was to investigate whether mutation in AMP
      activated protein kinase (AMPK) subunit genes (PRKAG3-230) is associated with
      sporadic, isolated Wolff-Parkinson-White (WPW) syndrome. METHODS: This study
      consisted of 87 patients with symptomatic WPW syndrome and 93 healthy controls.
      PRKAG3-230 genotypes were determined using real-time polymerase chain reaction
      assay. Genotype and allele frequencies of PRKAG3-230 between patients with WPW
      syndrome and healthy controls were ascertained using chi-square test or Fisher
      exact test when appropriate. RESULTS: PRKAG3-230 were genotyped in 87 patients
      (53 men and 34 women; age=24.4+/-18.0 years) with WPW syndrome and 93 healthy
      controls (57 men and 36 women; age=16.8+/-4.2 years). There were no significant
      differences between the two groups in terms of age and sex. The patients with CG
      and CG+CC genotypes had a significantly increased risk of WPW syndrome compared
      with those with GG genotype [odds ratio (OR)=1.99, 95% confidence interval
      (CI)=1.01-3.89, p=0.045; OR=1.99, 95% CI=1.04-3.78, p=0.037, respectively]. The
      allelic types were not associated with the risk of WPW syndrome. The patients
      with manifest type with CG and CG+CC genotypes had a significantly increased risk
      of WPW syndrome compared with those with GG genotype (OR=2.86, 95% CI=1.16-7.05,
      p=0.022; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The patients with
      right-side accessory pathways with CG and CG+CC genotypes had a significantly
      increased risk of WPW syndrome compared with those with GG genotype (OR=3.07, 95%
      CI=1.25-7.51, p=0.014; OR=2.84, 95% CI=1.19-6.80, p=0.019, respectively). The
      allelic types were not associated with the risk of WPW types and locations.
      CONCLUSION: This study shows that PRKAG3-230 may be associated with sporadic WPW
      syndrome among a Taiwanese population. Further studies are warranted to elucidate
      the role of mutations in AMPK subunit genes other than PRKAG3-230 in sporadic WPW
      syndrome.

PMID- 27866918
TI  - [Children and adolescents' anxiety disorders].
AB  - Anxiety disorders were long underestimated in children by healthcare
      professionals, but they are now better diagnosed. They account for the most
      frequent psychiatric diagnosis between 6 and 18 years of age, with differences in
      prevalence or risk factors related to the clinical forms. Different clinical
      subtypes of anxiety disorders are detailed in this article: separation anxiety,
      specific phobia, generalized anxiety, social anxiety, panic disorder, post
      traumatic stress syndrome, and obsessional-compulsive disorder. The repercussions
      of anxiety are often major on the psychological, relational, and developmental
      dimensions, as well as academics. Refusing school for reasons of anxiety is one
      of the possible and severe consequences of anxiety disorders, possibly resulting
      in total removal from school and the risk of early and permanent cessation of
      schooling. Other frequent complications are depression, and substance abuse
      during adolescence, as well as chronification of the disorders until adulthood.
      Indeed, adults affected by anxiety disorders frequently place the onset of their
      disorders at the beginning of adolescence. It is therefore essential to diagnose
      these disorders as soon as possible to set up an adapted therapeutic strategy.
      The main first-line treatment currently recommended in the pediatric population
      is cognitive and behavioral therapy, the efficacy of which has been the most
      clearly demonstrated. Psychoactive drugs can be used as a complement in severe or
      resistant cases, mainly serotonin recapture inhibitors.

PMID- 27866919
TI  - In vitro sensitivity of antimalarial drugs and correlation with clinico
      parasitological response following treatment with a 3-day artesunate-mefloquine
      combination in patients with falciparum malaria along the Thai-Myanmar border.
AB  - A 3-day artesunate-mefloquine combination therapy has been using as first-line
      treatment for acute uncomplicated Plasmodium falciparum malaria in Thailand since
      1995 on the background of mefloquine resistance. The aim of the present study was
      to assess sensitivity of P. falciparum isolates (n=44) in an area along the Thai
      Myanmar border (year 2009) to artesunate, mefloquine, chloroquine and quinine,
      including their correlation with clinico-parasitological response. Twenty, 19,
      and 5 isolates were collected from patients with 'Adequate Clinical and
      Parasitological Response (ACPR)', 'Late Parasitological Failure (LPF)' and 're
      infection', respectively. The IC50 of artesunate and mefloquine were
      significantly higher in patients with LPF compared with ACPR and re-infection.
      The proportion of isolates with declined artesunate or mefloquine sensitivity in
      the LPF group (47.4%) was significantly higher than the ACPR group (5.0%). A weak
      but statistical significant correlation (r=0.384, p=0.01) was observed between
      IC50 values of artesunate and parasite clearance time (PCT). There was no
      significant relationship between in vitro sensitivity of parasite isolates to
      chloroquine or quinine and clinical response. In vitro susceptibility of P.
      falciparum isolates to artesunate and mefloquine may be used as a useful reliable
      tool to predict clinico-pathological response following a 3-day artesunate
      mefloquine combination therapy.

PMID- 27866921
TI  - Models of evolution and evolutionary game theory: A comment on "Evolutionary game
      theory using agent based models" by Christoph Adami, Jory Schossau, Arend Hintze.

PMID- 27866920
TI  - The orphan nuclear receptor COUP-TFII coordinates hypoxia-independent
      proangiogenic responses in hepatic stellate cells.
AB  - BACKGROUND & AIMS: Hepatic stellate cell (HSC) transdifferentiation into collagen
      producing myofibroblasts is a key event in hepatic fibrogenesis, but the
      transcriptional network that controls the acquisition of the activated phenotype
      is still poorly understood. In this study, we explored whether the nuclear
      receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII)
      is involved in HSC activation and in the multifunctional role of these cells
      during the response to liver injury. METHODS: COUP-TFII expression was evaluated
      in normal and cirrhotic livers by immunohistochemistry and Western blot. The role
      of COUP-TFII in HSC was assessed by gain and loss of function transfection
      experiments and by generation of mice with COUP-TFII deletion in HSC. Molecular
      changes were determined by gene expression microarray and RT-qPCR. RESULTS: We
      showed that COUP-TFII is highly expressed in human fibrotic liver and in mouse
      models of hepatic injury. COUP-TFII expression rapidly increased upon HSC
      activation and it was associated with the regulation of genes involved in cell
      motility, proliferation and angiogenesis. Inactivation of COUP-TFII impairs
      proliferation and invasiveness in activated HSC and COUP-TFII deletion in mice
      abrogate HSC activation and angiogenesis. Finally, co-culture experiments with
      HSC and liver sinusoidal endothelial cells (SEC) showed that COUP-TFII expression
      in HSC influenced SEC migration and tubulogenesis via a hypoxia-independent and
      nuclear factor kappaB-dependent mechanism. CONCLUSION: This study elucidates a
      novel transcriptional pathway in HSC that is involved in the acquisition of the
      proangiogenic phenotype and regulates the paracrine signals between HSC and SEC
      during hepatic wound healing. LAY SUMMARY: In this study, we identified an
      important regulator of HSC pathobiology. We showed that the orphan receptor COUP
      TFII is an important player in hepatic neoangiogenesis. COUP-TFII expression in
      HSC controls the crosstalk between HSC and endothelial cells coordinating
      vascular remodelling during liver injury. TRANSCRIPT PROFILING: ArrayExpress
      accession E-MTAB-1795.

PMID- 27866922
TI  - Disease control framework based on spatial epidemiology: Reply to comments on
      "Pattern transitions in spatial epidemics: Mechanisms and emergent properties".

PMID- 27866923
TI  - How to avoid plagiarism, dual publication and data fragmentation.

PMID- 27866927
TI  - Mesenchymal stem cells transplantation during ex vivo lung perfusion.

PMID- 27866925
TI  - Extracorporeal membrane oxygenation support and post-heart transplant outcomes
      among United States adults.
AB  - BACKGROUND: Patients supported with extracorporeal membrane oxygenation (ECMO)
      are given priority listing status for heart transplant (HT). Data on post-HT
      outcomes for adults with ECMO support at the time of HT are limited. METHODS: We
      analyzed data from the United Network for Organ Registry (UNOS) registry for 157
      ECMO-supported adults (age >= 18 years) undergoing HT after January 1, 2000. Data
      at the time of HT were examined for their association with post-transplant
      mortality using multivariable Cox proportional hazard analyses. RESULTS: Patients
      (69.4% males; mean age, 46.0 +/- 15.6 years; 15.9% African Americans) were
      monitored for median of 0.55 years (interquartile range, 0.04-4.5). Seventy
      patients (44.6%) died during follow-up (survival at 1 year was 57.8%), of which
      43 (61.4%) died within 30 days post-HT. For patients surviving the first 30 days
      after transplant, long-term survival was acceptable (82.3% at 1 year and 76.2% at
      5 years). Prevalence of immediate post-HT complications, such as stroke and need
      for dialysis, were 10.1% and 28.1%, respectively. Post-HT survival did not differ
      between those who received an allograft before and after January 1, 2009
      (univariate hazard ratio, 0.84; 95% confidence interval, 0.51-1.38; p = 0.48).
      Among the predictors identified for 30-day and long-term mortality were recipient
      history of renal insufficiency (RI; defined as estimated glomerular filtration
      rate < 45 ml/min/1.73 m2 or dialysis) and mechanical ventilation (MV; interaction
      p < 0.05); those with both MV and RI had significantly poorer post-transplant
      survival (29.4% and 12.5% for 30-day and 1-year survival, respectively) compared
      with those without (78.7% and 71.4% for 30-day and 1-year survival,
      respectively). CONCLUSIONS: Post-HT mortality did not change for ECMO-supported
      adults in the contemporary era, and those with RI and MV had significantly poorer
      post-transplant survival. A critical review of priority listing status for ECMO
      supported patients is warranted for optimal allocation and outcomes of cardiac
      allografts.

PMID- 27866928
TI  - Improved waitlist and transplant outcomes for pediatric lung transplantation
      after implementation of the lung allocation score.
AB  - BACKGROUND: Although the lung allocation score (LAS) has not been considered
      valid for lung allocation to children, several additional policy changes for
      pediatric lung allocation have been adopted since its implementation. We compared
      changes in waitlist and transplant outcomes for pediatric and adult lung
      transplant candidates since LAS implementation. METHODS: The United Network for
      Organ Sharing database was reviewed for all lung transplant listings during the
      period 1995 to June 2014. Outcomes were analyzed based on date of listing (pre
      LAS vs post-LAS) and candidate age at listing (adults >18 years, adolescents 12
      to 17 years, children 0 to 11 years). RESULTS: Of the 39,962 total listings,
      2,096 (5%) were for pediatric candidates. Median waiting time decreased after LAS
      implementation for all age groups (adults: 379 vs 83 days; adolescents: 414 vs
      104 days; children: 211 vs 109 days; p < 0.001). The proportion of candidates
      reaching transplant increased after LAS (adults: 52.6% vs 71.6%, p < 0.001;
      adolescents: 40.3% vs 61.6%, p < 0.001; children: 42.4% vs 50.9%, p = 0.014),
      whereas deaths on the waitlist decreased (adults: 28.0% vs 14.4%, p < 0.001;
      adolescents: 33.1% vs 20.9%, p < 0.001; children: 32.2% vs 25.0%; p = 0.025),
      despite more critically ill candidates in all groups. Median recipient survival
      increased after LAS for adults and children (adults: 5.1 vs 5.5 years, p < 0.001;
      children: 6.5 vs 7.6 years, p = 0.047), but not for adolescents (3.6 vs 4.3
      years, p = 0.295). CONCLUSIONS: Improvements in waiting time, mortality and post
      transplant survival have occurred in children after LAS implementation. Continued
      refinement of urgency-based allocation to children and broader sharing of
      pediatric donor lungs may help to maximize these benefits.

PMID- 27866926
TI  - Evaluation of humoral immunity profiles to identify heart recipients at risk for
      development of severe infections: A multicenter prospective study.
AB  - BACKGROUND: New biomarkers are necessary to improve detection of the risk of
      infection in heart transplantation. We performed a multicenter study to evaluate
      humoral immunity profiles that could better enable us to identify heart
      recipients at risk of severe infections. METHODS: We prospectively analyzed 170
      adult heart recipients at 8 centers in Spain. Study points were before
      transplantation and 7 and 30 days after transplantation. Immune parameters
      included IgG, IgM, IgA and complement factors C3 and C4, and titers of specific
      antibody to pneumococcal polysaccharide antigens (anti-PPS) and to
      cytomegalovirus (CMV). To evaluate potential immunologic mechanisms leading to
      IgG hypogammaglobulinemia, before heart transplantation we assessed serum B-cell
      activating factor (BAFF) levels using enzyme-linked immunoassay. The clinical
      follow-up period lasted 6 months. Clinical outcome was need for intravenous anti
      microbials for therapy of infection. RESULTS: During follow-up, 53 patients
      (31.2%) developed at least 1 severe infection. We confirmed that IgG
      hypogammaglobulinemia at Day 7 (defined as IgG <600 mg/dl) is a risk factor for
      infection in general, bacterial infections in particular, and CMV disease. At Day
      7 after transplantation, the combination of IgG <600 mg/dl + C3 <80 mg/dl was
      more strongly associated with the outcome (adjusted odds ratio 7.40; 95%
      confidence interval 1.48 to 37.03; p = 0.014). We found that quantification of
      anti-CMV antibody titers and lower anti-PPS antibody concentrations were
      independent predictors of CMV disease and bacterial infections, respectively.
      Higher pre-transplant BAFF levels were a risk factor of acute cellular rejection.
      CONCLUSION: Early immunologic monitoring of humoral immunity profiles proved
      useful for the identification of heart recipients who are at risk of severe
      infection.

PMID- 27866924
TI  - Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions.
AB  - Research in recent years has focused significantly on the role of selective
      macroautophagy in targeting intracellular pathogens for lysosomal degradation, a
      process termed xenophagy. In this review we evaluate the proposed roles for
      xenophagy in controlling bacterial infection, highlighting the concept that
      successful pathogens have evolved ways to subvert or exploit this defense,
      minimizing the actual effectiveness of xenophagy in innate immunity. Instead,
      studies in animal models have revealed that autophagy-associated proteins often
      function outside of xenophagy to influence bacterial pathogenesis. In light of
      current efforts to manipulate autophagy and the development of host-directed
      therapies to fight bacterial infections, we also discuss the implications
      stemming from the complicated relationship that exists between autophagy and
      bacterial pathogens.

PMID- 27866930
TI  - Finding Ms or Mr Right: Which miRNA to target in AF?

PMID- 27866929
TI  - Long-term outcomes of pulmonary arterial hypertension under specific drug therapy
      in Eisenmenger syndrome.
AB  - BACKGROUND: The long-term effectiveness of pulmonary arterial hypertension
      specific drug therapy (PAH-SDT) in Eisenmenger syndrome is controversial. We
      investigated short-term and long-term hemodynamic changes under PAH-SDT and their
      associations with outcomes in a bicentric cohort. METHODS: Over 20 years, we
      included 69 patients with congenital heart disease, an indexed pulmonary vascular
      resistance (PVRi) >8 WU.m2, and 292 standardized catheterizations at baseline and
      after PAH-SDT initiation or intensification. Oxygen consumption was measured and
      the Fick principle applied to calculate indexed pulmonary output (Qpi) and PVRi.
      RESULTS: After PAH-SDT initiation or intensification, median (interquartile
      range) PVRi decrease was 5.1 WU.m2 (-1.4, -12.6) (p < 0.0001). Median Qpi and 6
      minute walk test increases were +0.4 liter/min/m2 (0.0, +0.9) (p < 0.0001) and
      +49 m (+15, +93) (p = 0.0003), respectively. Hemodynamic response combining
      increased Qpi with decreases in transpulmonary gradient and PVRi occurred in
      68.0% of patients. After a median of 4.9 years, PVRi and Qpi changes were no
      longer significant. Over a median of 7.2 years, 23 (33.3%) patients met a
      composite criterion (death, n = 8; heart-lung transplantation or listing for
      transplantation, n = 15). The 15-year cumulative event rate was 49.2%. By
      multivariate analysis, independent predictors of events were superior vena cava
      oxygen saturation and hemodynamic response (p = 0.048 and p < 0.0001).
      CONCLUSIONS: In Eisenmenger syndrome, PAH-SDT induces early hemodynamic
      improvements, which decline over time. Hemodynamic changes under PAH-SDT vary
      across patients. Hemodynamic parameters at baseline and under PAH-SDT are
      associated with events. PAH-SDT may need to be individualized based on
      hemodynamic changes.

PMID- 27866931
TI  - Key role of endothelium in the eNOS-dependent cardioprotection with exercise
      training.
AB  - Modulation of endothelial nitric oxide synthase (eNOS) activation is recognized
      as a main trigger of the cardioprotective effects of exercise training on heart
      vulnerability to ischemia-reperfusion (IR). However, this enzyme is expressed
      both in coronary endothelial cells and cardiomyocytes and the contribution of
      each one to such cardioprotection has never been challenged. The aim of this
      study was to investigate the role of eNOS from the cardiomyocytes vs. the
      endothelium in the exercise cardioprotection. Male Wistar rats were assigned to a
      chronic aerobic training (Ex) (vs. sedentary group; Sed) and we investigated the
      role of eNOS in the effects of exercise on sensitivity to IR or anoxia
      reoxygenation (A/R) at whole heart, isolated cardiomyocytes and left coronary
      artery (LCA) levels. We observed that exercise increased eNOS activation (Ser1177
      phosphorylation) and protein S-nitrosylation in whole heart but not at
      cardiomyocyte level, suggesting the specific target of endothelial cells by
      exercise. Consistently, in isolated cardiomyocytes submitted to the A/R
      procedure, exercise reduced cell death and improved cells contractility, but
      independently of the eNOS pathway. Next, to evaluate the contribution of
      endothelial cells in exercise cardioprotection, LCA were isolated before and
      after an IR procedure performed on Langendorff hearts. Exercise improved basal
      relaxation sensitivity to acetylcholine and markedly reduced the alteration of
      endothelium-dependent coronary relaxation induced by IR. Furthermore,
      inactivation of coronary endothelial cells activity just before IR, obtained with
      a bolus of Triton X-100, totally suppressed cardioprotective effects of exercise
      on both left ventricular functional recovery after IR and infarct size, whereas
      no effect of Triton X-100 was observed in Sed group. In conclusion, these results
      show that coronary endothelial cells rather than cardiomyocytes play a key role
      in the eNOS-dependent cardioprotection of exercise.

PMID- 27866932
TI  - Oxytocin attenuates aversive response to nicotine and anxiety-like behavior in
      adolescent rats.
AB  - Initial tobacco use is initiated with rewarding and aversive properties of
      nicotine and aversive response to nicotine plays a critical role in nicotine
      dependency. Decrease of nicotine aversion increases the nicotine use that causes
      behavioral and neuronal changes of animals. Oxytocin influences drug abuse and
      reciprocally affect vulnerability to drug use. To assess the effect of oxytocin
      on initial nicotine aversion and anxiety, we examined voluntary oral nicotine
      intake and anxiety-like behavior following oxytocin treatment in adolescent rats.
      Sprague-Dawley male rats (4 weeks old) were used. For oxytocin administration,
      rats were injected subcutaneously with saline or oxytocin (0.01, 0.1 and 1mg/kg)
      according to the assigned groups. Voluntary oral nicotine consumption test was
      performed by two bottle free-choice paradigm. To examine anxiety-like behavior in
      rats, we performed a light/dark box test. Oxytocin not only significantly
      increased the nicotine intake but also alleviated nicotine aversion after
      acclimation to nicotine solution in a concentration dependent manner. Meanwhile,
      oxytocin significantly reduced anxiety-like behavior. We suggest that oxytocin
      itself mitigates aversive response toward initial nicotine intake and anxiety
      like behavior. These results widen the psychophysiological perspective on
      oxytocin for better understanding of nicotine addiction related behaviors
      influenced by diverse social factors.

PMID- 27866933
TI  - Evaluation of the Tobacco Heating System 2.2 (THS2.2). Part 5: microRNA
      expression from a 90-day rat inhalation study indicates that exposure to THS2.2
      aerosol causes reduced effects on lung tissue compared with cigarette smoke.
AB  - Modified-risk tobacco products (MRTP) are designed to reduce the individual risk
      of tobacco-related disease as well as population harm compared to smoking
      cigarettes. Experimental proof of their benefit needs to be provided at multiple
      levels in research fields. Here, we examined microRNA (miRNA) levels in the lungs
      of rats exposed to a candidate modified-risk tobacco product, the Tobacco Heating
      System 2.2 (THS2.2) in a 90-day OECD TG-413 inhalation study. Our aim was to
      assess the miRNA response to THS2.2 aerosol compared with the response to
      combustible cigarettes (CC) smoke from the reference cigarette 3R4F. CC smoke
      exposure, but not THS2.2 aerosol exposure, caused global miRNA downregulation,
      which may be explained by the interference of CC smoke constituents with the
      miRNA processing machinery. Upregulation of specific miRNA species, such as miR
      146a/b and miR-182, indicated that they are causal elements in the inflammatory
      response in CC-exposed lungs, but they were reduced after THS2.2 aerosol
      exposure. Transforming transcriptomic data into protein activity based on
      corresponding downstream gene expression, we identified potential mechanisms for
      miR-146a/b and miR-182 that were activated by CC smoke but not by THS2.2 aerosol
      and possibly involved in the regulation of those miRNAs. The inclusion of miRNA
      profiling in systems toxicology approaches increases the mechanistic
      understanding of the complex exposure responses.

PMID- 27866934
TI  - Pharmacodynamic action and mechanism of Du Liang soft capsule, a traditional
      Chinese medicine capsule, on treating nitroglycerin-induced migraine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Du Liang soft capsule (DL) is a traditional
      Chinese medicine for treating migraines; it is made from two Chinese herbs,
      including LigusticumstriatumDC., root; Angelica dahurica (Hoffm.) Benth. &
      Hook.f. ex Franch. & Sav., root. AIM OF THE STUDY: In the present study, we aimed
      to elucidate the pharmacodynamic action of DL and its mechanism in an animal
      model of migraines induced by glyceryl trinitrate (GTN). MATERIALS AND METHODS:
      Sixty rats were randomly divided into six groups, including a normal control
      group, model control group, positive group (Sumatriptan 0.006gkg-1), and three DL
      groups (0.44, 1.31 and 3.93gkg-1). All rats were intragastrically treated with
      the corresponding treatment for 7 consecutive days, and they were subcutaneously
      injected with GTN (10mgkg-1) 30min after the last treatment, except in the normal
      control group. After model establishment, the behaviors of all rats, including
      head scratching, cage climbing, and the development of red ears were observed
      continuously by digital camera every 30min for 3h. Four hours after GTN
      treatment, all rats were anaesthetized and the blood and tissue samples were
      collected. Plasma calcitonin gene related to peptide (CGRP) and endothelin (ET)
      levels were measured using the radioimmunoassay method, and serum NO was
      determined by the colorimetric method. Afterwards, the brainstem tissues were
      dissected and washed with physiological saline, and divided evenly into two
      parts. One part was used to test the monoamine levels, including levels of 5
      hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA), by the
      fluorometric method, and the other part was used to determine the nuclear factor
      kappaB (NF-kappaB) p65, nuclear c-fos, inducible nitric oxide synthase (iNOS),
      interleukin (IL)-1beta (IL-1beta), and cyclooxygenase-2 (COX-2) levels by Western
      blot analysis. RESULTS: In the pharmacodynamic action assay, DL (1.31 and 3.93gkg
      1) greatly improved the abnormal behaviors of migraine rats, including head
      scratching and cage climbing, and the development of red ears. In the mechanism
      assay, compared with the control group, the plasma CGRP and serum NO levels and
      the brainstem 5-HT, NE and DA levels in the DL administration groups were
      significantly decreased; and the plasma ET levels were remarkably increased.
      Moreover, down-regulation of NF-kappaB p65, c-fos and pro-inflammatory cytokines,
      including iNOS, IL-1beta and COX-2 in the brainstem in the DL administration
      groups were observed by Western blot analysis. CONCLUSIONS: The above results
      suggested that DL has a therapeutic effect on migraines, and its mechanism may be
      related to adjusting the level of neurotransmitters and vasoactive substances,
      consequently relieving neurogenic inflammation.

PMID- 27866937
TI  - Antenatal foetal heart monitoring.
AB  - Antenatal foetal heart rate assessment was introduced into clinical medicine
      before clear evidence of any benefits had been reported. Ad hoc definitions were
      used to define normal and abnormal recordings resulting in a high false-positive
      rate for foetal compromise. The understanding of the foetal states resulted in an
      improved physiologically based assessment of the antenatal tracings and allowed
      their classification as (i) reactive - 2 accelerations in 10 min within a
      recording period of 120 min, (ii) unreactive - no accelerations seen in 120 min
      of tracing and (iii) decelerative - the presence of repetitive decelerations on
      an otherwise unreactive trace. This classification reduces the high rate of false
      positive traces associated with recording times of less than 40 min. Traces
      performed on pregnancies before 32 weeks predict clinical outcome, but need to be
      interpreted in light of the fact the many foetuses will not show a mature
      reactive pattern.

PMID- 27866936
TI  - Current applications and different approaches for microbial l-asparaginase
      production.
AB  - l-asparaginase (EC 3.5.1.1) is an enzyme that catalysis mainly the asparagine
      hydrolysis in l-aspartic acid and ammonium. This enzyme is presented in different
      organisms, such as microorganisms, vegetal, and some animals, including certain
      rodent's serum, but not unveiled in humans. It can be used as important
      chemotherapeutic agent for the treatment of a variety of lymphoproliferative
      disorders and lymphomas (particularly acute lymphoblastic leukemia (ALL) and
      Hodgkin's lymphoma), and has been a pivotal agent in chemotherapy protocols from
      around 30 years. Also, other important application is in food industry, by using
      the properties of this enzyme to reduce acrylamide levels in commercial fried
      foods, maintaining their characteristics (color, flavor, texture, security, etc.)
      Actually, l-asparaginase catalyzes the hydrolysis of l-asparagine, not allowing
      the reaction of reducing sugars with this aminoacid for the generation of
      acrylamide. Currently, production of l-asparaginase is mainly based in
      biotechnological production by using some bacteria. However, industrial
      production also needs research work aiming to obtain better production yields, as
      well as novel process by applying different microorganisms to increase the range
      of applications of the produced enzyme. Within this context, this mini-review
      presents l-asparaginase applications, production by different microorganisms and
      some limitations, current investigations, as well as some challenges to be
      achieved for profitable industrial production.

PMID- 27866938
TI  - Ovulation induction in polycystic ovary syndrome: Current options.
AB  - There are a variety of effective treatment options to induce ovulation in women
      with polycystic ovary syndrome (PCOS). The most effective treatments are
      primarily reproductive and target the hypothalamic-pituitary-ovarian (HPO) axis.
      Letrozole, an aromatase inhibitor, is headed toward replacing clomiphene, a
      selective estrogen receptor modulator, as the first-choice option. Metabolic
      treatments likely work indirectly through the HPO axis. Many metabolic treatments
      have shown initial promise and later failed (troglitozone or d-chiro-inositol) or
      disappointed (metformin); further studies are needed of newer agents to treat
      type 2 diabetes. Weight loss interventions, lifestyle related, through obesity
      drugs or through bariatric surgery have shown mixed results on pregnancy
      outcomes. With both reproductive and metabolic treatments, combination therapies
      (such as metformin and clomiphene together) may offer greater benefit to distinct
      subgroups of patients.

PMID- 27866939
TI  - [First case report of Streptococcus equi subsp. zooepidemicus post-infectious
      acute glomerulonephritis in France].
AB  - Post-infectious glomerulonephritis has become exceptional in France because
      streptococcus infections are well-treated. When they appear, clinical and
      biological symptoms are mostly typical and associate acute nephritic syndrome,
      acute renal failure, proteinuria, hematuria and low complement. We are reporting
      the first French case of acute post-infectious glomerulonephritis related to
      Streptococcus equi subsp. zooepidemicus, which is commonly found in horses and
      rarely in human pathology, and of which contamination is by direct contact with
      sick horses or by ingestion of non-pasteurized milk.

PMID- 27866940
TI  - Anterior pre-tensioned external fixator for pelvic fractures and dislocations.
      Initial clinical series.
AB  - In the treatment of unstable pelvic ring fractures, external fixators have the
      limitation of not adequately stabilizing the injured posterior elements. This
      article presents a novel and simple technique of temporary external fixation of
      the pelvic ring, able to produce compression of both the anterior and posterior
      pelvic elements. A curved flexible carbon-fiber rod is used, pre-tensioned before
      attachment to supra-acetabular Schanz screws. Although more extensive clinical
      experience is required, favorable preliminary results in a series of 13 patients
      with unstable pelvic fracture were encouraging: the aim of closing the posterior
      and anterior elements of the pelvic ring was achieved in all cases treated with
      this technique, and 12 patients survived. Radiological results were excellent in
      3 cases and good in 9 cases. No major complications, such as secondary
      displacement, vertical re-displacement or deep infection, were observed. Mean
      operative time was 25min, compatible with emergency management.

PMID- 27866941
TI  - Vayg1 is required for microsclerotium formation and melanin production in
      Verticillium dahliae.
AB  - The fungus Verticillium dahliae causes vascular wilt disease on many plant
      species, including economically important crop and ornamental plants worldwide.
      It produces darkly pigmented resting structures known as microsclerotia, which
      are able to survive for up to 14years in soil, and represent one of the defining
      characteristics of this species. The pigment produced in V. dahliae is
      dihydroxynaphthalene (DHN)-melanin, a form of melanin common among fungi and
      named so for the intermediary of this melanin biosynthetic pathway. In this
      study, we characterized the function of the V. dahliae Vayg1 gene, whose homologs
      were involved in melanin biosynthesis in Exophiala dermatitidis (Wayg1) and
      Aspergillus fumigatus (Aayg1), by deletion and complementation of the gene and co
      incubating deletion mutant with wild-type strain. Results showed that melanin
      production and microsclerotial formation in deletion mutants are inhibited. The
      Vayg1 deletion mutant also exhibited reduced pathogenicity. These results showed
      that Vayg1 is necessary for melanin and microsclerotium production, and we may
      thus hypothesize that the Vayg1 product may catalyze two different precursors,
      one of which is essential for DHN melanin production and the other one is
      involved in a signal network for microsclerotial formation in V. dahliae.

PMID- 27866942
TI  - A review of molecular genetic studies of neurocognitive deficits in
      schizophrenia.
AB  - Schizophrenia is a complex and debilitating illness with strong genetic loading.
      In line with its heterogeneous symptomatology, evidence suggests genetic
      etiologies for the phenotypes in schizophrenia. A search across endophenotypes
      has pointed towards consistent findings in its neurocognitive deficits. Extensive
      literature has demonstrated impaired cognition including executive function,
      attention, and memory in schizophrenia patients when compared to healthy
      subjects. This review (1) provides an overview of recent studies and (2) develops
      an up-to-date conceptualization of genetic variations influencing neurocognitive
      functions in schizophrenia patients. Several neurotransmitter system genes have
      been examined given knowledge of their role in brain functions and their reported
      genetic associations with schizophrenia and cognition. Several genetic variations
      have emerged as having preliminary effects on neurocognitive deficits in
      schizophrenia. These include genes in the neurotrophic, serotonin, cell adhesion,
      and sodium channel systems. Limited evidence also suggests the dopaminergic
      system genes, with the most studied catechol-o-methytransferase (COMT) gene
      showing inconsistent findings. Further investigations with larger samples and
      replications are required to elucidate genetic risk for cognitive deficits in
      schizophrenia.

PMID- 27866943
TI  - Enterobacteriaceae: joining the dots with pan-European epidemiology.

PMID- 27866945
TI  - A global call from five countries to collaborate in antibiotic stewardship:
      united we succeed, divided we might fail.
AB  - In February, 2016, WHO released a report for the development of national action
      plans to address the threat of antibiotic resistance, the catastrophic
      consequences of inaction, and the need for antibiotic stewardship. Antibiotic
      stewardship combined with infection prevention comprises a collaborative,
      multidisciplinary approach to optimise use of antibiotics. Efforts to mitigate
      overuse will be unsustainable without learning and coordinating activities
      globally. In this Personal View, we provide examples of international
      collaborations to address optimal prescribing, focusing on five countries that
      have developed different approaches to antibiotic stewardship-the USA, South
      Africa, Colombia, Australia, and the UK. Although each country's approach
      differed, when nurtured, individual efforts can positively affect local and
      national antimicrobial stewardship programmes. Government advocacy, national
      guidelines, collaborative research, online training programmes, mentoring
      programmes, and social media in stewardship all played a role. Personal
      relationships and willingness to learn from each other's successes and failures
      continues to foster collaboration. We recommend that antibiotic stewardship
      models need to evolve from infection specialist-based teams to develop and use
      cadres of health-care professionals, including pharmacists, nurses, and community
      health workers, to meet the needs of the global population. We also recommend
      that all health-care providers who prescribe antibiotics take ownership and
      understand the societal burden of suboptimal antibiotic use, providing examples
      of how countries can learn, act globally, and share best antibiotic stewardship
      practices.

PMID- 27866935
TI  - Diarrheagenic Escherichia coli.
AB  - Most Escherichia coli strains live harmlessly in the intestines and rarely cause
      disease in healthy individuals. Nonetheless, a number of pathogenic strains can
      cause diarrhea or extraintestinal diseases both in healthy and immunocompromised
      individuals. Diarrheal illnesses are a severe public health problem and a major
      cause of morbidity and mortality in infants and young children, especially in
      developing countries. E. coli strains that cause diarrhea have evolved by
      acquiring, through horizontal gene transfer, a particular set of characteristics
      that have successfully persisted in the host. According to the group of virulence
      determinants acquired, specific combinations were formed determining the
      currently known E. coli pathotypes, which are collectively known as diarrheagenic
      E. coli. In this review, we have gathered information on current definitions,
      serotypes, lineages, virulence mechanisms, epidemiology, and diagnosis of the
      major diarrheagenic E. coli pathotypes.

PMID- 27866944
TI  - Occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli
      in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a
      prospective, multinational study.
AB  - BACKGROUND: Gaps in the diagnostic capacity and heterogeneity of national
      surveillance and reporting standards in Europe make it difficult to contain
      carbapenemase-producing Enterobacteriaceae. We report the development of a
      consistent sampling framework and the results of the first structured survey on
      the occurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia
      coli in European hospitals. METHODS: National expert laboratories recruited
      hospitals with diagnostic capacities, who collected the first ten carbapenem non
      susceptible clinical isolates of K pneumoniae or E coli and ten susceptible same
      species comparator isolates and pertinent patient and hospital information.
      Isolates and data were relayed back to national expert laboratories, which made
      laboratory-substantiated information available for central analysis. FINDINGS:
      Between Nov 1, 2013, and April 30, 2014, 455 sentinel hospitals in 36 countries
      submitted 2703 clinical isolates (2301 [85%] K pneumoniae and 402 (15%) E coli).
      850 (37%) of 2301 K pneumoniae samples and 77 (19%) of 402 E coli samples were
      carbapenemase (KPC, NDM, OXA-48-like, or VIM) producers. The ratio of K
      pneumoniae to E coli was 11:1. 1.3 patients per 10 000 hospital admissions had
      positive clinical specimens. Prevalence differed greatly, with the highest rates
      in Mediterranean and Balkan countries. Carbapenemase-producing K pneumoniae
      isolates showed high resistance to last-line antibiotics. INTERPRETATION: This
      initiative shows an encouraging commitment by all participants, and suggests that
      challenges in the establishment of a continent-wide enhanced sentinel
      surveillance for carbapenemase-producing Enterobacteriaeceae can be overcome.
      Strengthening infection control efforts in hospitals is crucial for controlling
      spread through local and national health care networks. FUNDING: European Centre
      for Disease Prevention and Control.

PMID- 27866946
TI  - Systems Genetics Approach Identifies Gene Pathways and Adamts2 as Drivers of
      Isoproterenol-Induced Cardiac Hypertrophy and Cardiomyopathy in Mice.
AB  - We previously reported a genetic analysis of heart failure traits in a population
      of inbred mouse strains treated with isoproterenol to mimic catecholamine-driven
      cardiac hypertrophy. Here, we apply a co-expression network algorithm, wMICA, to
      perform a systems-level analysis of left ventricular transcriptomes from these
      mice. We describe the features of the overall network but focus on a module
      identified in treated hearts that is strongly related to cardiac hypertrophy and
      pathological remodeling. Using the causal modeling algorithm NEO, we identified
      the gene Adamts2 as a putative regulator of this module and validated the
      predictive value of NEO using small interfering RNA-mediated knockdown in
      neonatal rat ventricular myocytes. Adamts2 silencing regulated the expression of
      the genes residing within the module and impaired isoproterenol-induced cellular
      hypertrophy. Our results provide a view of higher order interactions in heart
      failure with potential for diagnostic and therapeutic insights.

PMID- 27866947
TI  - Integrating GWAS and Co-expression Network Data Identifies Bone Mineral Density
      Genes SPTBN1 and MARK3 and an Osteoblast Functional Module.
AB  - Bone mineral density (BMD) is a highly heritable predictor of osteoporotic
      fracture. Genome-wide association studies (GWAS) for BMD have identified dozens
      of associations; yet, the genes responsible for most associations remain elusive.
      Here, we used a bone co-expression network to predict causal genes at BMD GWAS
      loci based on the premise that genes underlying a disease are often functionally
      related and functionally related genes are often co-expressed. By mapping genes
      implicated by BMD GWAS onto a bone co-expression network, we predicted and
      inferred the function of causal genes for 30 of 64 GWAS loci. We experimentally
      confirmed that two of the genes predicted to be causal, SPTBN1 and MARK3, are
      potentially responsible for the effects of GWAS loci on chromosomes 2p16.2 and
      14q32.32, respectively. This approach provides a roadmap for the dissection of
      additional BMD GWAS associations. Furthermore, it should be applicable to GWAS
      data for a wide range of diseases.

PMID- 27866949
TI  - Perioperative Periprosthetic Fractures Associated With Primary Total Hip
      Arthroplasty.
AB  - BACKGROUND: Periprosthetic fracture (PPF) is a rare but devastating complication
      of primary total hip arthroplasty (THA). While PPF is associated with increased
      morbidity and mortality, early revision rate, and poor patient outcome, there is
      a paucity of data on patient and hospital-dependent risk factors. Using a large
      administrative database, we investigated epidemiology and the risk factors
      associated with perioperative PPF after primary THA. METHODS: We performed a
      retrospective review of the National Inpatient Sample records from 2006 to 2011
      and identified 1062 PPFs of 1,187,969 patients using International Classification
      of Diseases, Ninth Revision code for PPF (996.44). We then analyzed
      sociodemographic characteristics, comorbidities, and hospital characteristics of
      our study population. RESULTS: The overall incidence of PPF in National Inpatient
      Sample database was 0.089% (8.9 per 10,000 THAs). Patient-dependent risk factors
      were: female (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.67-2.22), low
      household income (OR 1.4, 95% CI 1.18-1.65), Medicaid (OR 1.89, 95% CI 1.39
      2.57), and uninsured (OR 2.74, 95% CI 1.63-4.61). Patients with malnutrition and
      hemiparesis/hemiplegia were associated 10-fold and 6-fold risk of PPF.
      Nonteaching hospitals (OR 1.15, 95% CI 1.01-1.32), hospitals in northeast (OR
      1.29, 95% CI 1.04-1.59), and rural hospitals (OR 1.27, 95% CI 1.06-1.53) had
      higher incidence of PPF. CONCLUSION: Our study demonstrates that the incidence of
      PPF was low in our study population, and greater awareness is needed when
      performing primary THAs in patients with risk factors identified in our study to
      prevent PPF.

PMID- 27866948
TI  - Pulmonary Embolism Rates Following Total Hip Arthroplasty With Prophylactic
      Anticoagulation: Some Pulmonary Emboli Cannot Be Avoided.
AB  - BACKGROUND: A symptomatic pulmonary embolism (PE) after total joint arthroplasty
      has been described as a "never event." Despite potent anticoagulants and
      improvements in patient care, PE continues to occur following total hip
      arthroplasty (THA). This study evaluates symptomatic PE rates over time in THA
      patients enrolled in multicenter randomized clinical trials (RCTs) assessing the
      efficacy of venous thromboembolism prophylaxis regimens. METHODS: The MEDLINE and
      Cochrane Central Register of Controlled Trials were searched to identify clinical
      trials assessing prophylactic anticoagulation in patients undergoing THA between
      January 1995 and December 2015. Inclusion criteria consisted of RCTs evaluating
      prophylactic anticoagulation in patients undergoing THA. A random effect model
      was used to combine PE rates across studies. RESULTS: A total of 21 studies
      (34,764 patients) were included. Patients were administered low molecular weight
      heparin (13,590 patients), oral factor Xa inhibitors (6609 patients), oral direct
      thrombin inhibitors (5965 patients), indirect factors Xa/IIa inhibitors (3444
      patients), aspirin (2427 patients), and warfarin (489 patients). Mobile
      compression was used in 199 patients, and placebo was used in 2041 patients.
      Across all included studies, the estimated PE rate was 0.21% (95% confidence
      interval: 0.13%, 0.32%). Between 1997 and 2013, the proportion of PEs did not
      change in regression analysis. CONCLUSION: Although the PE rate was low, it was
      consistent throughout the 17 years spanning these RCTs, which excluded patients
      with significant morbidity. These results suggest that even healthy THA patients
      receiving aggressive anticoagulation still have a risk for PE, and the "never
      event" designation requires reassessment.

PMID- 27866950
TI  - Cause-Specific Mortality Trends Following Total Hip and Knee Arthroplasty.
AB  - BACKGROUND: While studies have demonstrated that mortality after total hip (THA)
      and total knee (TKA) arthroplasty is better than the general population, the
      causes of death are not well established. We evaluated cause-specific mortality
      after THA and TKA. METHODS: The study included population-based cohorts of
      patients who underwent THA (N = 2019) and TKA (N = 2259) between 1969 and 2008.
      Causes of death were classified using the International Classification of
      Diseases 9th and 10th editions. Cause-specific standardized mortality ratios
      (SMR) and 95% confidence intervals (CI) were calculated by comparing observed and
      expected mortality. Expected mortality was derived from mortality rates in the
      United States white population of similar calendar year, age, and sex
      characteristics. RESULTS: All-cause mortality was lower than expected following
      both THA and TKA. However, there was excess mortality due to mental diseases such
      as dementia following both THA (SMR 1.40, 95% CI 1.08, 1.80) and TKA (SMR 1.49,
      95% CI 1.19, 1.85). There was also excess mortality from inflammatory
      musculoskeletal diseases in THA (SMR 3.50, 95% CI 2.11, 5.46) and TKA (SMR 4.85,
      95% CI 3.29, 6.88). When the cohorts were restricted to patients with
      osteoarthritis as the surgical indication, the excess risk of death from mental
      diseases still persisted in THA (SMR 1.36, 95% CI 1.02, 1.78) and TKA (SMR 1.52,
      95% CI 1.20, 1.91). CONCLUSION: THA and TKA patients experience a higher risk of
      death from mental and inflammatory musculoskeletal diseases. These findings
      warrant further research to identify drivers of mortality and prevention
      strategies in arthroplasty patients.

PMID- 27866951
TI  - The Incidence and Economic Burden of In-Hospital Venous Thromboembolism in the
      United States.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a potentially preventable and costly
      complication after total hip arthroplasty (THA) and total knee arthroplasty
      (TKA). The in-hospital incidence and economic burden of VTE following total joint
      arthroplasty (TJA) in the United States is unknown. The aim of this study was to
      examine this issue. METHODS: The Nationwide Inpatient Sample was used to estimate
      the total number of THA, TKA, and VTE events using International Classification
      of Diseases, Ninth Revision procedure codes from years 2002 to 2011. The rate of
      in-hospital deep vein thrombosis (DVT) and pulmonary embolism (PE), associated
      length of hospitalization, and current and projected in-hospital charges were
      obtained. RESULTS: Revision arthroplasties had higher rates of in-hospital VTE
      compared to primary TJAs (2.5% vs 1.6%, P < .0001). Among primary TJAs, the
      median rate of in-hospital VTE was 0.59% (0.55%-0.63%) for primary THA and 1.01%
      (0.94%-1.08%) for primary TKA. Revision THAs developed more VTE events compared
      to revision TKAs (1.35% [1.25%-1.46%] vs 1.16% [1.07%-1.26%]). Patients with a
      VTE have longer hospitalizations (median primary TKA: 7 vs 3; median primary THA:
      6 vs 3, P < .0001). The overall rate of VTE decreased over the last decade;
      however, the PE rates have remained relatively constant. Moreover, the associated
      costs with VTE events have increased significantly over the last decade.
      CONCLUSION: Based on the analysis of the Nationwide Inpatient Sample database,
      the rate of in-hospital DVT following TJA appears to have declined over the last
      decade while the incidence of PE has remained constant. This may indicate that
      the current recommendations by the American Academy of Orthopaedic Surgeons for
      VTE prophylaxis are adequate for preventing DVT without increasing the rate of PE
      or that institutional screening and reporting of DVT has been reduced because
      DVTs became a "never" event.

PMID- 27866952
TI  - Recent Trends in Blood Utilization After Primary Hip and Knee Arthroplasty.
AB  - BACKGROUND: Blood conservation strategies have evolved greatly over the last 5
      years. There is a paucity of large blood utilization studies of total hip
      arthroplasty (THA) and total knee arthroplasty (TKA) that include recently
      performed surgery. The purpose of this study was to use a large database to
      evaluate trends in blood transfusion after THA and TKA, including 2015 data.
      METHODS: The Humana data set was reviewed from 2007 to the third quarter of 2015
      for all patients undergoing primary THA and TKA. Rates and type of postoperative
      blood transfusion were trended through the years of the data set. Further
      subgroup analysis was performed to evaluate the impact of patients' age, gender,
      geographic location, and obesity on the incidence of blood transfusion using
      standard statistical techniques. RESULTS: In total, 69,350 THA patients and
      139,804 TKA patients were analyzed. Overall transfusion rate was 18.2% and 12.7%
      after TKA and THA, respectively. The most common type of blood transfused was
      allogeneic packed red blood cells (88% of all transfusions) followed by
      perioperative collected autologous blood (12% of all transfusions). There were no
      transfusions of preoperatively collected autologous blood. Transfusion rates
      decreased significantly from 21.3%-8.7% and 17.3%-4.4% for THA and TKA,
      respectively, over the years 2007-2015 (P < .001). CONCLUSION: Rates of blood
      transfusion after primary THA and TKA have fallen precipitously since 2010 and
      are now down to 9% and 4% for THA and TKA, respectively. Blood management
      strategies instituted over the last 5 years have had a large impact on
      transfusion rates after joint arthroplasty.

PMID- 27866953
TI  - Triple-tandem high-dose-rate brachytherapy for early-stage medically inoperable
      endometrial cancer: Initial report on acute toxicity and dosimetric comparison to
      stereotactic body radiation therapy.
AB  - PURPOSE: Stereotactic body radiotherapy (SBRT) may be appealing in medically
      inoperable endometrial cancer to avoid procedural risks. We performed a
      dosimetric comparison to triple-tandem, high-dose-rate (HDR) brachytherapy.
      METHODS AND MATERIALS: Six consecutive clinical stage I, grade 1-2, medically
      inoperable endometrial cancer patients were treated with triple-tandem HDR
      brachytherapy. We report patient factors and acute toxicity. Also, we performed
      dosimetric comparison to SBRT using both 3D conformal arc (3DArc) and volumetric
      modulated arc therapy. D2cc values for normal tissues were calculated and
      compared to the HDR plans. RESULTS: Median age was 57 years. Patient
      comorbidities included morbid obesity, congestive heart failure, diabetes, and
      pulmonary emboli. In three patients who received prior external beam radiation
      (EBRT), median EBRT and HDR doses were 46 Gy and 20 Gy, respectively. The median
      dose with HDR brachytherapy monotherapy was 35 Gy. Acute toxicities during EBRT
      included gastrointestinal (3/3 with grade 1-2) and genitourinary (3/3 with grade
      1-2). Acute toxicities during HDR brachytherapy were gastrointestinal (2/6 total
      with grade 1-2) and genitourinary (2/6 total with grade 1). The mean D2cc/Gy of
      prescription dose for rectum, sigmoid, and bladder were 0.58, 0.40, and 0.47
      respectively. Overall, doses to normal tissues were higher for SBRT plans as
      compared to HDR. Also, the R50 (ratio of the 50% prescription isodose volume to
      the PTV) was lowest with HDR brachytherapy. CONCLUSIONS: In medically inoperable,
      clinical stage I endometrial cancer patients with multiple comorbidities,
      definitive triple-tandem, HDR brachytherapy results in mild acute toxicity. In
      addition, HDR brachytherapy achieves relatively lower doses to surrounding normal
      tissues as compared to SBRT.

PMID- 27866955
TI  - Analysis of the power profile of a new soft contact lens for myopia progression.

PMID- 27866954
TI  - The Enright phenomenon. Stereoscopic distortion of perceived driving speed
      induced by monocular pupil dilation.
AB  - PURPOSE: The Enright phenomenon describes the distortion in speed perception
      experienced by an observer looking sideways from a moving vehicle when viewing
      with interocular differences in retinal image brightness, usually induced by
      neutral density filters. We investigated whether the Enright phenomenon could be
      induced with monocular pupil dilation using tropicamide. METHODS: We tested 17
      visually normal young adults on a closed road driving circuit. Participants were
      asked to travel at Goal Speeds of 40km/h and 60km/h while looking sideways from
      the vehicle with: (i) both eyes with undilated pupils; (ii) both eyes with
      dilated pupils; (iii) with the leading eye only dilated; and (iv) the trailing
      eye only dilated. For each condition we recorded actual driving speed. RESULTS:
      With the pupil of the leading eye dilated participants drove significantly faster
      (by an average of 3.8km/h) than with both eyes dilated (p=0.02); with the
      trailing eye dilated participants drove significantly slower (by an average of
      3.2km/h) than with both eyes dilated (p<0.001). The speed, with the leading eye
      dilated, was faster by an average of 7km/h than with the trailing eye dilated
      (p<0.001). There was no significant difference between driving speeds when
      viewing with both eyes either dilated or undilated (p=0.322). CONCLUSIONS: Our
      results are the first to show a measurable change in driving behaviour following
      monocular pupil dilation and support predictions based on the Enright phenomenon.

PMID- 27866957
TI  - Gender and the circadian pattern of body temperature in normoxia and hypoxia.
AB  - Circadian patterns are at the core of many physiological processes, and their
      disruption can have short- and long-term consequences. This essay focuses on one
      of the best known patterns, the daily oscillation of body temperature (Tb), and
      the possibility of its difference between genders. From human and animal studies
      globally considered, the tentative conclusion is reached that differences in Tb
      circadian pattern between genders are very small and probably limited to the
      timing of the rhythm, not to its amplitude. Such similarity between genders,
      despite the differences in hormonal systems, presumably testifies to the
      importance that the Tb circadian pattern plays in the economy of the organism and
      its survival against environmental challenges. The second part of the article
      presents some previously unpublished experimental data from behaving male and
      female rats during hypoxia in synchronized conditions. In adult rats hypoxia
      (10.5% O2 for three days) caused a profound drop of the Tb daily oscillations; by
      day 3 they were 55% (?) and 22% (?) of the normoxic amplitudes, with a
      statistically significant gender difference. In pre-puberty rats (26-day old)
      hypoxia caused a major disruption of the circadian pattern qualitatively similar
      to the adults but not different between genders. Hence, on the basis of this
      preliminary set of data, it seems that sex-hormones may be a factor in how the Tb
      daily pattern responds to hypoxia. The implications of the effects of hypoxia on
      the circadian patterns, and the possibility that such effects may differ between
      genders, are matters that could have biological and clinical implications and
      deserve further investigations.

PMID- 27866956
TI  - Accuracy and completeness of drug information in Wikipedia medication monographs.
AB  - OBJECTIVES: The primary objective of this study was to determine the accuracy and
      completeness of drug information on Wikipedia and Micromedex compared with U.S.
      Food and Drug Administration-approved U.S. product inserts. METHODS: The top 10
      brand and top 10 generic medications from the 2012 Institute for Health
      Informatics' list of top 200 drugs were selected for evaluation. Wikipedia
      medication information was evaluated and compared with Micromedex in 7 sections
      of drug information; the U.S. product inserts were used as the standard
      comparator. RESULTS: Wikipedia demonstrated significantly lower completeness and
      accuracy scores compared with Micromedex (mean composite scores 18.55 vs. 38.4,
      respectively; P <0.01). No difference was found between the mean composite scores
      for brand versus generic drugs in either reference (17.8 vs. 19.3, respectively
      [P = 0.62], for Wikipedia; 39.2 vs. 37.6, [P = 0.06] for Micromedex). Limitations
      to these results include the speed with which information is edited on Wikipedia,
      that there was no evaluation of off-label information, and the limited number of
      drugs that were evaluated. CONCLUSION: Wikipedia lacks the accuracy and
      completeness of standard clinical references and should not be a routine part of
      clinical decision making. More research should be conducted to evaluate the
      rationale for health care providers' use of Wikipedia.

PMID- 27866958
TI  - Use of Concomitant Stress Incontinence Surgery at Time of Pelvic Organ Prolapse
      Surgery Since Release of the 2011 Notification on Serious Complications
      Associated with Transvaginal Mesh.
AB  - PURPOSE: There is controversy regarding the performance of concomitant anti
      incontinence procedures at the time of pelvic organ prolapse repair. Data support
      improvement in stress urinary incontinence with a concomitant sling but increased
      adverse events. We assessed trends in preoperative stress urinary incontinence
      evaluation, concomitant anti-incontinence procedure at pelvic organ prolapse
      surgery and postoperative anti-incontinence procedures at our institution before
      and after the 2011 FDA (U.S. Food and Drug Administration) Public Health
      Notification pertaining to vaginal mesh. MATERIALS AND METHODS: We
      retrospectively reviewed the records of patients who underwent pelvic organ
      prolapse surgery from 2009 to 2015. Preoperative workup included assessment of
      subjective stress urinary incontinence and/or evaluation for leakage with
      reduction of pelvic organ prolapse on physical examination, urodynamics or a
      pessary trial. The percentages of concomitant and postoperative anti-incontinence
      procedures were compared before and after the 2011 FDA notification. RESULTS: A
      total of 775 women underwent pelvic organ prolapse repair. The percentage of anti
      incontinence procedures at pelvic organ prolapse repair decreased from 54.8% to
      38.0% after the FDA notification (p = 0.002) while the incidence of preoperative
      objective stress urinary incontinence on examination, urodynamics and pessary
      trials remained constant. The incidence of postoperative anti-incontinence
      procedures within 1 year of the index surgery remained low. CONCLUSIONS: We found
      a decrease in the incidence of concomitant anti-incontinence procedures at the
      time of pelvic organ prolapse repair following the 2011 FDA notification despite
      no significant decline in subjective stress urinary incontinence or demonstrable
      stress urinary incontinence on preoperative evaluation. Further analysis is
      warranted to assess the impact of the FDA notification on treatment patterns in
      women with pelvic organ prolapse and stress urinary incontinence.

PMID- 27866959
TI  - Evaluating the risk of hypertension according to the metabolic health status
      stratified by degree of obesity.
AB  - Despite the accumulated evidence showing the significant association between
      hypertension and obesity, it remains unclear how metabolic healthy status of
      obesity have an impact on the development of hypertension. Thus, this study was
      to investigate the risk of hypertension according to the metabolic healthy status
      stratified by the degree of obesity. A cohort of 25,442 Korean men without
      hypertension at baseline was followed-up from 2005 to 2010. They were divided
      into the following 6 phenotypes according to their baseline metabolic health and
      obesity status: metabolically healthy normal weight (MH-NW), metabolically
      healthy overweight (MH-OW), metabolically healthy obese (MHO), metabolically
      unhealthy normal weight (MU-NW), metabolically unhealthy overweight (MU-OW), and
      metabolically unhealthy obese (MUO). Cox proportional hazard model was used to
      evaluate the risk for hypertension according to the metabolically healthy status
      stratified by degree of obesity. During 91,256.4 person-years of follow-up, 4633
      participants (18.2%) developed hypertension. The adjusted hazard ratios (95%
      confidence intervals) for hypertension in MH-OW, MHO, MU-NW, MU-OW, and MUO
      phenotypes compared with MH-NW phenotype were 1.13 (1.04-1.23), 1.43 (1.15-1.69),
      1.17 (1.02-1.34), 1.49 (1.27-1.72), and 1.54 (1.36-1.88), respectively. The
      interaction between metabolically healthy status and degree of obesity was not
      significant (P for interaction = .29). Compared with MH-NW, both the obese
      phenotype and metabolically unhealthy phenotype independently had an increased
      risk for hypertension. These results imply that both metabolic health status and
      obesity status play important roles independently in the risk of hypertension in
      Korean men.

PMID- 27866960
TI  - Ethanol-seeking behavior is expressed directly through an extended amygdala to
      midbrain neural circuit.
AB  - Abstinent alcohol-dependent individuals experience an enduring sensitivity to cue
      induced craving and relapse to drinking. There is considerable evidence
      indicating that structures within the midbrain and extended amygdala are involved
      in this process. Individually, the ventral tegmental area (VTA) and the bed
      nucleus of the stria terminalis (BNST) have been shown to modulate cue-induced
      ethanol-seeking behavior. It is hypothesized that cue-induced seeking is
      communicated through a direct projection from the BNST to VTA. In the current
      experiments, an intersectional viral strategy was used in DBA/2J mice to
      selectively target and inhibit BNST projections to the VTA during a test of
      ethanol conditioned place preference (CPP). Inhibitory designer receptors
      exclusively activated by designer drugs (hM4Di DREADDs) were expressed in VTA
      projecting BNST (BNST-VTA) cells by infusing a retrograde herpes-simplex virus
      encoding cre recombinase (HSV-Cre) into VTA and a cre-inducible adeno-associated
      virus encoding hM4Di (AAV-DIO-hM4Di) into BNST. Before testing the expression of
      preference, clozapine-N-oxide (CNO) was peripherally administered to activate
      hM4Di receptors and selectively inhibit these cells. Ethanol CPP expression was
      blocked by CNO-mediated inhibition of BNST-VTA cells. A follow-up study revealed
      this effect was specific to CNO activation of hM4Di as saline- and CNO-treated
      mice infused with a control vector (HSV-GFP) in place of HSV-Cre showed
      significant CPP. These findings establish a role for a direct BNST input to VTA
      in cue-induced ethanol-seeking behavior.

PMID- 27866961
TI  - Paradoxical results of two automated real-time PCR assays in the diagnosis of
      pleural tuberculosis.
AB  - Tuberculosis (TB) is a major cause of worldwide mortality. We report the case of
      a non-HIV-infected woman with clinical suspicion of pleural tuberculosis and
      contradictory results between Xpert(r) MTB/RIF and Abbott RealTime MTB assays
      from pleural fluid specimen. Liquid and solid cultures for tuberculosis were
      performed with negative results. The patient received treatment, and clinical
      improvement was observed. Both techniques detect Mycobacterium tuberculosis
      complex, but they have different targets and limits of detection. Abbott RealTime
      MTB results correlated well with the clinical findings of the patient.

PMID- 27866962
TI  - Distribution of muscarinic acetylcholine receptor subtypes in the murine small
      intestine.
AB  - AIMS: Serotonin stimulates enterocyte turnover in the small intestine and studies
      suggest this is mediated by neuronal signaling via a cholinergic pathway.
      Distribution of the five known muscarinic receptor subtypes (mAChRs) in the small
      intestine has not been fully studied, and their role in intestinal growth is
      unknown. We hypothesized that mAChRs have distinct anatomic distributions within
      the bowel, and that mAChRs present within intestinal crypts mediate the effects
      of acetylcholine on the small intestinal mucosa. MAIN METHODS: Small intestine
      from male C57BL/6 mice ages 2, 4, 6, and 8weeks were harvested. RNA was isolated
      and cDNA synthesized for PCR-amplification of subtype specific mAChRs. Ileum was
      fixed with Nakane, embedded in epon, and immunofluorescence microscopy performed
      using polyclonal antibodies specific to each mAChR1-5. KEY FINDINGS: All five
      mAChR subtypes were present in the mouse duodenum, jejunum, and ileum at all ages
      by RT-PCR. Immunofluorescence microscopy suggested the presence of mAChR1-5 in
      association with mature enterocytes along the villus and within the myenteric
      plexus. Only mAChR2 clearly localized to the crypt stem cell compartment,
      specifically co-localizing with Paneth cells at crypt bases. SIGNIFICANCE:
      Muscarinic receptors are widely distributed along the entire alimentary tract.
      mAChR2 appears to localize to the crypt stem cell compartment, suggesting it is a
      plausible regulator of stem cell activity. The location of mAChR2 to the crypt
      makes it a potential therapeutic target for treatment of intestinal disease such
      as short bowel syndrome. The exact cellular location and action of each mAChR
      requires further study.

PMID- 27866963
TI  - Interdialytic Weight Gain: Trends, Predictors, and Associated Outcomes in the
      International Dialysis Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: High interdialytic weight gain (IDWG) is associated with adverse
      outcomes in hemodialysis (HD) patients. We identified temporal and regional
      trends in IDWG, predictors of IDWG, and associations of IDWG with clinical
      outcomes. STUDY DESIGN: Analysis 1: sequential cross-sections to identify
      facility- and patient-level predictors of IDWG and their temporal trends.
      Analysis 2: prospective cohort study to assess associations between IDWG and
      mortality and hospitalization risk. SETTING & PARTICIPANTS: 21,919 participants
      on HD therapy for 1 year or longer in the Dialysis Outcomes and Practice Patterns
      Study (DOPPS) phases 2 to 5 (2002-2014). PREDICTORS: Analysis 1: study phase,
      patient demographics and comorbid conditions, HD facility practices. Analysis 2:
      relative IDWG, expressed as percentage of post-HD weight (<0%, 0%-0.99%, 1%
      2.49%, 2.5%-3.99% [reference], 4%-5.69%, and >=5.7%). OUTCOMES: Analysis 1:
      relative IDWG as a continuous variable using linear mixed models; analysis 2:
      mortality; all-cause and cause-specific hospitalization using Cox regression,
      adjusting for potential confounders. RESULTS: From phase 2 to 5, IDWG declined in
      the United States (-0.29kg; -0.5% of post-HD weight), Canada (-0.25kg; -0.8%),
      and Europe (-0.22kg; -0.5%), with more modest declines in Japan and Australia/New
      Zealand. Among modifiable factors associated with IDWG, the most notable was
      facility mean dialysate sodium concentration: every 1-mEq/L greater dialysate
      sodium concentration was associated with 0.13 (95% CI, 0.11-0.16) greater
      relative IDWG. Compared to relative IDWG of 2.5% to 3.99%, there was elevated
      risk for mortality with relative IDWG>=5.7% (adjusted HR, 1.23; 95% CI, 1.08
      1.40) and elevated risk for fluid-overload hospitalization with relative IDWG>=4%
      (HRs of 1.28 [95% CI, 1.09-1.49] and 1.64 [95% CI, 1.27-2.13] for relative IDWGs
      of 4%-5.69% and >=5.7%, respectively). LIMITATIONS: Possible residual
      confounding. No dietary salt intake data. CONCLUSIONS: Reductions in IDWG during
      the past decade were partially explained by reductions in dialysate sodium
      concentration. Focusing quality improvement strategies on reducing occurrences of
      high IDWG may improve outcomes in HD patients.

PMID- 27866965
TI  - Proton Pump Inhibitor Use and Risk of Hip Fracture in Kidney Transplant
      Recipients.
AB  - BACKGROUND: Posttransplantation bone disease is a significant problem, with few
      well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated
      with hip fracture in the general population and are widely prescribed for kidney
      transplant recipients. STUDY DESIGN: A case-control study. SETTING &
      PARTICIPANTS: From the US Renal Data System, we identified from diagnoses and
      procedures 231 kidney transplant recipients with a first hip fracture. Cases were
      matched at the hip fracture index date with 15,575 controls on age, sex, race,
      and transplantation year. PREDICTOR: PPI use. OUTCOMES: First hip fracture.
      RESULTS: In the year prior to the index date, a PPI was prescribed to 65.4% of
      cases and 57.4% of controls. Additionally, in 34.6% of cases and 28.9% of
      controls, a PPI was prescribed for >80% of the year preceding the index date
      (higher PPI users). Unadjusted ORs of hip fracture associated with any and higher
      PPI use were 1.55 (95% CI, 1.18-2.05) and 1.65 (95% CI, 1.2-2.27), respectively.
      When adjusted for baseline demographic, clinical, and pharmacologic covariables,
      any and higher PPI use remained associated with hip fracture, with ORs of 1.39
      (95% CI, 1.04-1.84) and 1.41 (95% CI, 1.02-1.95), respectively. LIMITATIONS:
      Potential residual confounding through either incorrectly ascertained or
      unavailable confounders; cohort limited to Medicare beneficiaries receiving low
      income subsidy. CONCLUSIONS: In summary, PPI use was associated with hip fracture
      risk in the US kidney transplant population.

PMID- 27866966
TI  - Complications of Vascular Access: Superior Vena Cava Syndrome.
AB  - Stenosis or occlusion of central veins in hemodialysis patients is common,
      especially with previous intravascular catheter or device use. Superior vena cava
      (SVC) obstruction is emerging as a frequent chronic complication of central vein
      cannulation that not only jeopardizes the availability of vascular access for
      hemodialysis, but can become a life-threatening emergency. Clinical features of
      SVC syndrome can be subtle or dramatic, including facial swelling and shortness
      of breath, which require expeditious attention and intervention. The approach to
      SVC syndrome involves judicious use of imaging techniques to define the cause and
      location. Early management with endovascular intervention with angioplasty and
      stent placement is the usual first choice. The occlusion can often be recanalized
      using new techniques such as radiofrequency wire and then salvaged with stents,
      providing prompt resolution of symptoms. Limitations to interventions include
      requirement of cutting-edge equipment, expertise, expense, and the usually
      temporary nature of the resolution. Surgery is considered the treatment of last
      resort for refractory cases. SVC syndrome can be prevented by minimizing catheter
      and intravascular device use through early recognition of patients with chronic
      kidney disease, early referral for education about all choices for kidney
      replacement modalities, and early placement of arteriovenous access prior to the
      onset of dialysis therapy.

PMID- 27866964
TI  - Dialysate Potassium, Serum Potassium, Mortality, and Arrhythmia Events in
      Hemodialysis: Results From the Dialysis Outcomes and Practice Patterns Study
      (DOPPS).
AB  - BACKGROUND: Sudden death is a leading cause of death in patients on maintenance
      hemodialysis therapy. During hemodialysis sessions, the gradient between serum
      and dialysate levels results in rapid electrolyte shifts, which may contribute to
      arrhythmias and sudden death. Controversies exist about the optimal electrolyte
      concentration in the dialysate; specifically, it is unclear whether patient
      outcomes differ among those treated with a dialysate potassium concentration of 3
      mEq/L compared to 2 mEq/L. STUDY DESIGN: Prospective cohort study. SETTING &
      PARTICIPANTS: 55,183 patients from 20 countries in the Dialysis Outcomes and
      Practice Patterns Study (DOPPS) phases 1 to 5 (1996-2015). PREDICTOR: Dialysate
      potassium concentration at study entry. OUTCOMES: Cox regression was used to
      estimate the association between dialysate potassium concentration and both all
      cause mortality and an arrhythmia composite outcome (arrhythmia-related
      hospitalization or sudden death), adjusting for potential confounders. RESULTS:
      During a median follow-up of 16.5 months, 24% of patients died and 7% had an
      arrhythmia composite outcome. No meaningful difference in clinical outcomes was
      observed for patients treated with a dialysate potassium concentration of 3
      versus 2 mEq/L (adjusted HRs were 0.96 [95% CI, 0.91-1.01] for mortality and 0.98
      [95% CI, 0.88-1.08] for arrhythmia composite). Results were similar across
      predialysis serum potassium levels. As in prior studies, higher serum potassium
      level was associated with adverse outcomes. However, dialysate potassium
      concentration had only minimal impact on serum potassium level measured
      predialysis (+0.09 [95% CI, 0.05-0.14] mEq/L serum potassium per 1 mEq/L greater
      dialysate potassium concentration). LIMITATIONS: Data were not available for
      delivered (vs prescribed) dialysate potassium concentration and postdialysis
      serum potassium level; possible unmeasured confounding. CONCLUSIONS: In
      combination, these results suggest that approaches other than altering dialysate
      potassium concentration (eg, education on dietary potassium sources and
      prescription of potassium-binding medications) may merit further attention to
      reduce risks associated with high serum potassium levels.

PMID- 27866967
TI  - Cryofibrinogen-Associated Glomerulonephritis.
AB  - Cryofibrinogen is an under-recognized cryoprotein. Cryofibrinogen is a
      cryoprecipitate that develops following plasma refrigeration, but does not occur
      in cold serum. People with cryofibrinogenemia may be asymptomatic, but this
      cryoprotein can be associated with thromboembolic disease, particularly affecting
      the skin. Kidney manifestations are relatively uncommon, but are likely
      underestimated. We describe clinical features and kidney biopsy results in 2
      patients with cryofibrinogen-related kidney disease. Both patients presented with
      proteinuria and hematuria. One had significant cutaneous ulcers and palpable
      purpura. Kidney biopsy in both cases showed membranoproliferative
      glomerulonephritis with no immunoglobulin deposition. Weak segmental capillary
      wall fibrinogen staining was noted in glomeruli. Immunofluorescence studies
      following pronase digestion failed to reveal masked immunoglobulin deposits.
      Ultrastructural studies were distinctive and characterized by organized deposits
      of large-bore with multilayered tubular structures and fine fibrillary structures
      in a matrix. To confirm the composition of deposits, we extracted the
      cryoprecipitate from plasma of a patient and performed ultrastructural studies,
      which showed identical ultrastructural characteristics to those seen on the
      kidney biopsy. We also performed proteomic analysis of the cryoprecipitate that
      confirmed the presence of fibrinogen. Subsequent laboratory evaluation was
      positive for cryofibrinogen in both patients on multiple occasions. Appropriate
      therapy was instituted in both patients, which included prednisone,
      immunosuppressive therapy, and avoidance of cold exposure. In summary, we present
      clinical, kidney biopsy, and laboratory findings and the treatment and follow-up
      of cryofibrinogen-associated glomerulonephritis. Awareness of this entity will
      result in accurate diagnoses, appropriate investigation, and treatment.

PMID- 27866968
TI  - Vasectomy Reversal Surgical Patterns: An Analysis of the American Board of
      Urology Case Logs.
AB  - OBJECTIVE: To characterize vasectomy reversal practice patterns among American
      Board of Urology (ABU) certifying urologists. MATERIALS AND METHODS: We reviewed
      the ABU case logs for certifying urologists from 2008 to 2014. Vasectomy reversal
      procedures were identified by 3 current procedure terminology (CPT) codes: 55400
      (vasovasostomy), 54900 (epididymovasostomy, unilateral), and 54901
      (epididymovasostomy, bilateral). Demographic data were obtained and reviewed.
      Multivariate analysis determined the factors influencing the performance of
      surgical approach. RESULTS: There were 5167 urologists who submitted case logs
      for 2008-2014, and 9.4% (486) had performed at least one vasectomy reversal
      procedure. General urologists accounted for the highest overall volume of
      vasectomy reversal procedures. Andrology-trained urologists performed a higher
      volume of vasovasostomy per surgeon, and bilateral epididymovasostomy constituted
      a greater portion of their E-V practice. Multivariate analysis demonstrated that
      being in recertification years, being younger in age, practicing in the South
      Central, Southeast, and Western regions, and practicing in the largest and
      smallest practice areas were associated with being more likely to perform a
      vasectomy reversal procedure. CONCLUSION: Microsurgical vasectomy reversals are
      putatively considered technically challenging and reserved for fellowship-trained
      urologists, and the majority of vasectomy reversal surgeries were performed by
      general urologists. Given the known association between microsurgical technique
      and improved outcomes, greater emphasis should be placed on microsurgical
      training during urology residency.

PMID- 27866969
TI  - Overexpression of CD109 in the Epidermis Differentially Regulates ALK1 Versus
      ALK5 Signaling and Modulates Extracellular Matrix Synthesis in the Skin.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor
      involved in many physiological processes including wound healing and
      inflammation. Excessive TGF-beta signaling in the skin has been implicated in
      fibrotic skin disorders such as keloids and scleroderma. We previously identified
      CD109 as a TGF-beta co-receptor and inhibitor of TGF-beta signaling and have
      shown that transgenic mice overexpressing CD109 in the epidermis display
      decreased scarring. In certain cell types, in addition to the canonical type I
      receptor, ALK5, which activates Smad2/3, TGF-beta can signal through another type
      I receptor, ALK1, which activates Smad1/5. Here we demonstrate that ALK1 is
      expressed and co-localizes with CD109 in mouse keratinocytes and that mice
      overexpressing CD109 in the epidermis display enhanced ALK1-Smad1/5 signaling but
      decreased ALK5-Smad2/3 signaling, TGF-beta expression, and extracellular matrix
      production in the skin when compared with wild-type littermates. Furthermore,
      treatment with conditioned media from isolated keratinocytes or epidermal
      explants from CD109 transgenic mouse skin leads to a decrease in extracellular
      matrix production in mouse skin fibroblasts. Taken together, our findings suggest
      that CD109 differentially regulates TGF-beta-induced ALK1-Smad1/5 versus ALK5
      Smad2/3 pathways, leading to decreased extracellular matrix production in the
      skin and that epidermal CD109 expression regulates dermal function through a
      paracrine mechanism.

PMID- 27866971
TI  - Snapping knee caused by the thickening of the medial hamstrings.
AB  - We report a case of symptomatic subluxation of the semitendinosus and gracilis
      over the medial condyle of the tibia caused by the thickening of its tendons.
      Snapping was reproduced on active extension. Clinical examination and, above all,
      dynamic ultrasound were the key for the diagnosis because other imaging tests
      were normal. Due to failure of conservative treatment with physiotherapy and
      infiltrations, surgery was undertaken, involving desinsertion and excision of
      distal 8cm segment of the semitendinosus and gracilis tendons. At the present
      time (6 months postoperatively), the patient is symptom-free and has returned to
      the previous normal life activities.

PMID- 27866970
TI  - Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association
      of rs2470102 with Skin Pigmentation.
AB  - Our understanding of the genetics of skin pigmentation has been largely skewed
      towards populations of European ancestry, imparting less attention to South Asian
      populations, who behold huge pigmentation diversity. Here, we investigate skin
      pigmentation variation in a cohort of 1,167 individuals in the Middle Gangetic
      Plain of the Indian subcontinent. Our data confirm the association of rs1426654
      with skin pigmentation among South Asians, consistent with previous studies, and
      also show association for rs2470102 single nucleotide polymorphism. Our haplotype
      analyses further help us delineate the haplotype distribution across social
      categories and skin color. Taken together, our findings suggest that the social
      structure defined by the caste system in India has a profound influence on the
      skin pigmentation patterns of the subcontinent. In particular, social category
      and associated single nucleotide polymorphisms explain about 32% and 6.4%,
      respectively, of the total phenotypic variance. Phylogeography of the associated
      single nucleotide polymorphisms studied across 52 diverse populations of the
      Indian subcontinent shows wide presence of the derived alleles, although their
      frequencies vary across populations. Our results show that both polymorphisms
      (rs1426654 and rs2470102) play an important role in the skin pigmentation
      diversity of South Asians.

PMID- 27866972
TI  - Letrozole regulates actin cytoskeleton polymerization dynamics in a SRC-1
      dependent manner in the hippocampus of mice.
AB  - In the hippocampus, local estrogens (E2) derived from testosterone that is
      catalyzed by aromatase play important roles in the regulation of hippocampal
      neural plasticity, but the underlying mechanisms remain unclear. The actin
      cytoskeleton contributes greatly to hippocampal synaptic plasticity; however,
      whether it is regulated by local E2 and the related mechanisms remain to be
      elucidated. In this study, we first examined the postnatal developmental profiles
      of hippocampal aromatase and specific proteins responsible for actin cytoskeleton
      dynamics. Then we used aromatase inhibitor letrozole (LET) to block local E2
      synthesis and examined the changes of these proteins and steroid receptor
      coactivator-1 (SRC-1), the predominant coactivator for steroid nuclear receptors.
      Finally, SRC-1 specific RNA interference was used to examine the effects of SRC-1
      on the expression of these actin remodeling proteins. The results showed a V-type
      profile for aromatase and increased profiles for actin cytoskeleton proteins in
      both male and female hippocampus without obvious sex differences. LET treatment
      dramatically decreased the F-actin/G-actin ratio, the expression of Rictor,
      phospho-AKT (ser473), Profilin-1, phospho-Cofilin (Ser3), and SRC-1 in a dose
      dependent manner. In vitro studies demonstrated that LET induced downregulation
      of these proteins could be reversed by E2, and E2 induced increase of these
      proteins were significantly suppressed by SRC-1 shRNA interference. These results
      for the first time clearly demonstrated that local E2 inhibition could induce
      aberrant actin polymerization; they also showed an important role of SRC-1 in the
      mediation of local E2 action on hippocampal synaptic plasticity by regulation of
      actin cytoskeleton dynamics.

PMID- 27866973
TI  - Fluorescent rare earth solutions as intrinsic wavelength standards for protein
      fluorescence spectroscopy.
AB  - Trivalent Gd, Tm, and Dy solutions can be used as intrinsic excitation and
      emission standards to validate the UV and violet-blue wavelength accuracy of a
      spectrofluorimeter. Europium extends the range into the red. To attain sufficient
      sensitivity, these luminescent rare earth ions require deuterated reagents or
      carbonate complexation, which allow the use of ordinary water and thus
      preparation in virtually any laboratory. Such solutions are particularly valuable
      as system suitability standards (SST) for protein fluorescence spectroscopy to
      detect red shifts of the intrinsic fluorescence maximum in stability and storage
      studies.

PMID- 27866975
TI  - Expression of stem cell markers in oral cavity and oropharynx squamous cell
      carcinoma.
AB  - OBJECTIVES: The aim of this study was to analyze the expression of CD24, CD44,
      CD133, ALDH1, CD29 (integrin-beta1), and Ki-67 in squamous cell carcinoma of the
      oral cavity and oropharynx. STUDY DESIGN: Fifty-two tumors and 21 metastatic
      lymph nodes were evaluated by using immunohistochemistry. RESULTS: Seven of 52
      cases (13.5%) showed positive cytoplasmic staining of aldehyde dehydrogenase 1;
      integrin-beta1 was expressed in 45 of 50 cases (90%); 30 of 52 cases (57.7%) had
      positive membranous staining of CD44; CD24 was expressed in 44 of 50 cases (88%);
      and three of 52 cases (5.8%) stained positively for membranous CD133. Median
      proliferation rate, measured by Ki-67, was 37.1% for tumors. Five-year cancer
      specific survival rates for the CD44-negative and CD44-positive groups were 74%
      and 38%, respectively, although this difference did not reach statistical
      significance (P = .052). CONCLUSIONS: Our study demonstrated the expression of
      putative stem cell markers in squamous cell carcinoma of the oral cavity and
      oropharynx, with participation of CD44-positive cells in association with poor
      survival outcome.

PMID- 27866976
TI  - Protective effect of rosiglitazone against acetaminophen-induced acute liver
      injury is associated with down-regulation of hepatic NADPH oxidases.
AB  - The peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand
      activated nuclear receptor that regulates glucose and lipid metabolism. The aim
      of the present study was to investigate the effects of rosiglitazone (RSG), a
      synthetic PPAR-gamma agonist, on acetaminophen (APAP)-induced acute liver injury.
      Male CD-1 mice were injected with APAP (300mg/kg). Some mice were pretreated with
      RSG (20mg/kg) 48, 24 and 1h before APAP injection. As expected, RSG pretreatment
      alleviated APAP-induced acute liver injury. Moreover, RSG pretreatment attenuated
      APAP-induced hepatic cell death and improved the survival. Although it did not
      affect hepatic cytochrome P450 (CYP)2E1 expression, RSG pretreatment attenuated
      reduction of hepatic glutathione peroxidase (GSH-Px), glutathione reductase (GSH
      Rd) and glutathione S-transferase (GST) activities, inhibited upregulation of
      hepatic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-2 and
      NOX-4, and alleviated hepatic GSH depletion during APAP-induced acute liver
      injury. In addition, RSG pretreatment suppressed activation of hepatic nuclear
      factor kappa B (NF-kappaB) and extracellular signal-related kinase (ERK)/mitogen
      activated protein kinase (MAPK) signaling during APAP-induced acute liver injury.
      These results provide a novel mechanistic explanation for RSG-mediated protection
      against APAP-induced acute liver injury. The present results suggest that
      synthetic PPAR-gamma agonists might be effective agents for preventing the
      progression of APAP-induced acute liver injury.

PMID- 27866977
TI  - The anti-hyperplasia, anti-oxidative and anti-inflammatory properties of Qing Ye
      Dan and swertiamarin in testosterone-induced benign prostatic hyperplasia in
      rats.
AB  - Qing Ye Dan (QYD) is the whole plant of Swertia mileensis and used in Chinese
      folk medicine for the treatment of prostatitis, benign prostatic hyperplasia
      (BPH) and so on. This study was to investigate the effects of QYD and its main
      component swertiamarin on BPH induced by testosterone in rats. The prostatic
      expressions of vascular endothelial growth factor (VEGF), epidermal growth factor
      (EGF), basic fibroblast growth factor (betaFGF) and proliferating cell nuclear
      antigen (PCNA) were detected by immunohistochemistry assay. Prostatic levels of
      oxidative stress and inflammatory-related factors were also analyzed.
      Additionally, the prostatic expressions of androgen receptor (AR), estrogen
      receptor (ER)-alpha, ER-beta, hypoxia-inducible factor (HIF)-1alpha, B-cell
      CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by
      western blot. The epithelial-mesenchymal transition (EMT) associated factors were
      evaluated by quantitative RT-PCR. It showed that QYD and swertiamarin ameliorated
      the testosterone-induced prostatic hyperplasia and collagen deposition,
      attenuated the over-expressions of HIF-1alpha, VEGF, EGF, betaFGF, PCNA, AR and
      ER-alpha, reduced the ratio of Bcl-2/Bax, enhanced the expression of ER-beta,
      inhibited the oxidative stress and local inflammation, as well as relieved
      prostatic EMT. It suggested that QYD and swertiamarin had prostatic protective
      potential against BPH.

PMID- 27866978
TI  - Stability and structural properties of gene regulation networks with coregulation
      rules.
AB  - Coregulation of the expression of groups of genes has been extensively
      demonstrated empirically in bacterial and eukaryotic systems. Such coregulation
      can arise through the use of shared regulatory motifs, which allow the
      coordinated expression of modules (and module groups) of functionally related
      genes across the genome. Coregulation can also arise through the physical
      association of multi-gene complexes through chromosomal looping, which are then
      transcribed together. We present a general formalism for modeling coregulation
      rules in the framework of Random Boolean Networks (RBN), and develop specific
      models for transcription factor networks with modular structure (including module
      groups, and multi-input modules (MIM) with autoregulation) and multi-gene
      complexes (including hierarchical differentiation between multi-gene complex
      members). We develop a mean-field approach to analyse the dynamical stability of
      large networks incorporating coregulation, and show that autoregulated MIM and
      hierarchical gene-complex models can achieve greater stability than networks
      without coregulation whose rules have matching activation frequency. We provide
      further analysis of the stability of small networks of both kinds through
      simulations. We also characterize several general properties of the transients
      and attractors in the hierarchical coregulation model, and show using simulations
      that the steady-state distribution factorizes hierarchically as a Bayesian
      network in a Markov Jump Process analogue of the RBN model.

PMID- 27866979
TI  - Species tree estimation using Neighbor Joining.
AB  - Recent theoretical work has demonstrated that Neighbor Joining applied to
      concatenated DNA sequences is a statistically consistent method of species tree
      reconstruction. This brief note compares the accuracy of this approach to other
      popular statistically consistent species tree reconstruction algorithms including
      ASTRAL-II Neighbor Joining using average gene-tree internode distances (NJst) and
      SVD-Quartets+PAUP*, as well as concatenation using maximum likelihood (RaxML). We
      find that the faster Neighbor Joining, applied to concatenated sequences, is
      among the most effective of these methods for accurate species tree
      reconstruction.

PMID- 27866980
TI  - Spherical agglomerates of lactose with enhanced mechanical properties.
AB  - The aim of this study was to prepare spherical agglomerates of lactose and to
      evaluate their physicochemical properties, flow properties, particle friability
      and compaction properties, and to compare them to commercially available types of
      lactose for direct compression (spray-dried, granulated and anhydrous beta
      lactose). Porous spherical agglomerates of alpha-lactose monohydrate with
      radially arranged prism-like primary particles were prepared exhibiting a high
      specific surface area. All types of lactose analysed had passable or better flow
      properties, except for anhydrous beta-lactose, which had poor flowability.
      Particle friability was more pronounced in larger granulated lactose particles;
      however, particle structure was retained in all samples analysed. The mechanical
      properties of spherical agglomerates of lactose, in terms of compressibility,
      established with Walker analysis, and compactibility, established with a
      compactibility profile, were found to be superior to any commercially available
      types of lactose. Higher compactibility of spherical agglomerates of lactose is
      ascribed to significantly higher particle surface area due to a unique internal
      structure with higher susceptibility to fragmentation.

PMID- 27866974
TI  - Sphingolipids in neutrophil function and inflammatory responses: Mechanisms and
      implications for intestinal immunity and inflammation in ulcerative colitis.
AB  - Bioactive sphingolipids are regulators of immune cell function and play critical
      roles in inflammatory conditions including ulcerative colitis. As one of the
      major forms of inflammatory bowel disease, ulcerative colitis pathophysiology is
      characterized by an aberrant intestinal inflammatory response that persists
      causing chronic inflammation and tissue injury. Innate immune cells play an
      integral role in normal intestinal homeostasis but their dysregulation is thought
      to contribute to the pathogenesis of ulcerative colitis. In particular,
      neutrophils are key effector cells and are first line defenders against invading
      pathogens. While the activity of neutrophils in the intestinal mucosa is required
      for homeostasis, regulatory mechanisms are equally important to prevent
      unnecessary activation. In ulcerative colitis, unregulated neutrophil
      inflammatory mechanisms promote tissue injury and loss of homeostasis. Aberrant
      neutrophil function represents an early checkpoint in the detrimental cycle of
      chronic intestinal inflammation; thus, dissecting the mechanisms by which these
      cells are regulated both before and during disease is essential for understanding
      the pathogenesis of ulcerative colitis. We present an analysis of the role of
      sphingolipids in the regulation of neutrophil function and the implication of
      this relationship in ulcerative colitis.

PMID- 27866981
TI  - Multiple coexistence equilibria in a two parasitoid-one host model.
AB  - Briggs et al. (1993) introduced a host-parasitoid model for the dynamics of a
      system with two parasitoids that attack different juvenile stages of a common
      host. Their main result was that coexistence of the parasitoids is only possible
      when there is sufficient variability in the maturation delays of the host
      juvenile stages. Here, we analyze the phenomenon of coexistence in that model
      more deeply. We show that with some distribution families for the maturation
      delays, the coexistence equilibrium is unique, while with other distributions
      multiple coexistence equilibria can be found. In particular, we find that stable
      coexistence does not necessarily require mutual invasibility.

PMID- 27866983
TI  - Downregulation of cytochrome c oxidase subunit 7A1 expression is important in
      enhancing cell proliferation in adenocarcinoma cells.
AB  - Mitochondrial Dysfunction has been implicated in multiple human diseases,
      including cancer. Among all cancer, lung cancer is the most common type of cancer
      worldwide with low survival rates. Mammals possess multiple subunits of the
      mitochondrial enzyme Cytochrome C oxidase (COX). The COX subunits are expressed
      in a tissue specific manner and have been implicated in cancer cell metabolism
      although their molecular and regulatory mechanisms are not clearly understood. In
      this study, we aimed at identifying novel gene signatures in lung cancer. We
      performed extensive analysis of seven different Gene Expression Omnibus (GEO)
      datasets pertaining to different stages of lung adenocarcinoma and identified
      that multiple subunits of COX genes are differentially expressed in these
      patients. Amongst all COX genes, the expression of COX7A1 gene was observed to be
      highly down regulated in these patients. In order to validate the GEO datasets,
      we looked at the expression of multiple COX genes using quantitative real time
      PCR (qPCR) using human lung adenocarcinoma cell line A549. Our results confirmed
      that COX 7A1 gene expression was indeed highly reduced in these cells.
      Overexpression of COX7A1 in human lung cancer cells led to inhibition of cell
      proliferation and increase in cell death via apoptosis. These results indicated
      that low level of COX7A1 gene expression is essential to regulate cell viability
      and inhibit cell death in lung adenocarcinoma. Our study has identified COX7A1 as
      a novel gene that might play a crucial role in the etiology of lung
      adenocarcinoma and can serve as a biomarker for lung cancer disease progression.

PMID- 27866982
TI  - Structure of the NS5 methyltransferase from Zika virus and implications in
      inhibitor design.
AB  - Recent outbreak of flavivirus Zika virus (ZIKV) in America has urged the basic as
      well as translational studies of this important human pathogen. The nonstructural
      protein 5 (NS5) of the flavivirus has an N-terminal methyltransferase (MTase)
      domain that plays critical roles in viral RNA genome capping. The null mutant of
      NS5 MTase is lethal for virus. Therefore, NS5 is a potential drug target for the
      treatment of Zika virus infection. In this study, we determined crystal
      structures of the ZIKV MTase in complex with GTP and RNA cap analogue 7meGpppA.
      Structural analyses revealed highly conserved GTP/cap-binding pocket and S
      adenosylmethionine (SAM)-binding pocket. Two conformations of the second base of
      the cap were identified, which suggests the flexibility of RNA conformation. In
      addition, the ligand-binding pockets identified a continuous region of hotspots
      suitable for drug design. Docking calculation shows that the Dengue virus
      inhibitor compound 10 may bind to the ZIKV MTase.

PMID- 27866985
TI  - Identification of functional bitter taste receptors and their antagonist in
      chickens.
AB  - Elucidation of the taste sense of chickens is important not only for the
      development of chicken feedstuffs for the chicken industry but also to help
      clarify the evolution of the taste sense among animals. There are three putative
      chicken bitter taste receptors, chicken T2R1 (cT2R1), cT2R2 and cT2R7, which were
      identified using genome information and cell-based assays. Previously, we have
      shown that cT2R1 is a functional bitter taste receptor through both cell-based
      assays and behavioral tests. In this study, therefore, we focused on the
      sensitivities of the other two bitter receptors, cT2R2 and cT2R7, by using their
      agonists in behavioral tests. We tested three agonists of cT2R2 and three
      agonists of cT2R7. In a 10-min drinking study, the intakes of cT2R2 agonist
      solutions were not different from that of water. On the other hand, the intakes
      of cT2R7 agonist solutions were significantly lower compared to water. In
      addition, we constructed cT2R1-and cT2R7-expressing cells in order to search for
      an antagonist for these functional bitter taste receptors. By using Ca2+ imaging
      methods, we found that 6-methoxyflavanone (6-meth) can inhibit the activities of
      both cT2R1 and cT2R7. Moreover, 6-meth also inhibited the reduction of the intake
      of bitter solutions containing cT2R1 or cT2R7 agonists in behavioral tests. Taken
      together, these results suggested that cT2R7 is a functional bitter taste
      receptor like cT2R1, but that cT2R2 is not, and that 6-meth is an antagonist for
      these two functional chicken bitter taste receptors. This is the first
      identification of an antagonist of chicken bitter receptors.

PMID- 27866984
TI  - p53R2 regulates thioredoxin reductase activity through interaction with TrxR2.
AB  - Ribonucleotide reductase small subunit p53R2 is a member of the ribonucleotide
      reductase family that supplies dNTPs for nuclear and mitochondrial DNA
      replication and repair. Here, we have identified a mitochondrial thioredoxin
      reductase 2 (TrxR2) as a novel p53R2-binding protein. We demonstrated a direct
      interaction between the two, and observed that p53R2 stimulated the enzymatic
      activity of TrxR in vitro. Moreover, TrxR2 activity was significantly lower in
      p53R2 knockdown cells, and increased when p53R2 was overexpressed, effects that
      were independent of p53. Furthermore, p53R2 knockdown suppressed UV-induced TrxR
      activity. These findings suggest that p53R2 acts as a positive regulator of TrxR2
      activity in mitochondria both under normal physiological conditions and during
      the cellular response to DNA damage.

PMID- 27866986
TI  - Modelling of in-vitro and in-vivo performance of aerosol emitted from different
      vibrating mesh nebulisers in non-invasive ventilation circuit.
AB  - Substituting nebulisers by another in non-invasive ventilation circuit (NIV)
      involves many process variables which must be adjusted to ensure patient optimum
      therapy. However, there is a doubt when nebulisers use the same technology. Data
      mining technology based on artificial neural networks and genetic algorithms were
      used here to model in-vitro inhalation process and predict bioavailability from
      inhaled doses delivered by three different vibrating mesh nebulisers (VMNs) in
      NIV. Modelling of data indicated that in-vitro performance of VMNs was dependent
      mainly on fine particle fraction, mass median aerodynamic diameter (MMAD), total
      emitted dose (TED) and to lesser extent on nebuliser type. Ex-vivo model
      indicated that amount of salbutamol collected on facemask filter was directly
      affected by TED. In-vivo model showed that amount of salbutamol deposited into
      the lung (0.5hQ) and amount absorbed systemically (24hQ) were dependent directly
      on MMAD and TED. Female patients showed higher 24hQ values than males. Nebuliser
      type affected TED, 0.5hQ but not 24hQ values. Results indicate suitability of
      VMNs in achieving appropriate in-vitro inhalation performance model. The results
      also, indicate that the three VMNs are comparable and can be interchanged with no
      fear of any additional toxicity.

PMID- 27866987
TI  - Signalling product healthiness through symbolic package cues: Effects of package
      shape and goal congruence on consumer behaviour.
AB  - Three studies show that product packaging shape serves as a cue that communicates
      healthiness of food products. Inspired by embodiment accounts, we show that
      packaging that simulates a slim body shape acts as a symbolic cue for product
      healthiness (e.g., low in calories), as opposed to packaging that simulates a
      wide body shape. Furthermore, we show that the effect of slim package shape on
      consumer behaviour is goal dependent. Whereas simulation of a slim (vs. wide)
      body shape increases choice likelihood and product attitude when consumers have a
      health-relevant shopping goal, packaging shape does not affect these outcomes
      when consumers have a hedonic shopping goal. In Study 3, we adopt a realistic
      shopping paradigm using a shelf with authentic products, and find that a slim (as
      opposed to wide) package shape increases on-shelf product recognition and
      increases product attitude for healthy products. We discuss results and
      implications regarding product positioning and the packaging design process.

PMID- 27866988
TI  - The effects of partial sleep restriction and altered sleep timing on appetite and
      food reward.
AB  - : We examined the effects of partial sleep restriction (PSR) with an advanced
      wake-time or delayed bedtime on measures of appetite, food reward and subsequent
      energy intake (EI). Twelve men and 6 women (age: 23 +/- 4 years, body fat: 18.8
      +/- 10.1%) participated in 3 randomized crossover sessions: control (habitual bed
      and wake-time), 50% PSR with an advanced wake-time and 50% PSR with a delayed
      bedtime. Outcome variables included sleep architecture (polysomnography), ad
      libitum EI (validated food menu), appetite sensations (visual analogue scales),
      satiety quotient (SQ; mm/100 kcal) and food reward (Leeds Food Preference
      Questionnaire and the relative-reinforcing value (RRV) of preferred food task).
      Increased fasting and post-standard breakfast appetite ratings were noted
      following PSR with an advanced wake-time compared to the control and PSR with a
      delayed bedtime sessions (Fasting hunger ratings: 77 +/- 16 vs. 65 +/- 18 and 64
      +/- 16; P = 0.01; Post-meal hunger AUC: 5982 +/- 1781 vs. 4508 +/- 2136 and 5198
      +/- 2201; P = 0.03). Increased explicit wanting and liking for high- relative to
      low-fat foods were also noted during the advanced wake-time vs. control session
      (Explicit wanting: -3.5 +/- 12.5 vs. -9.3 +/- 8.9, P = 0.01; Explicit liking: 
      1.6 +/- 8.5 vs. -7.8 +/- 9.6, P = 0.002). No differences in the RRV of preferred
      food, SQ and ad libitum lunch intake were noted between sessions. These findings
      suggest that appetite sensations and food reward are increased following PSR with
      an advanced wake-time, rather than delayed bedtime, vs. CONTROL: However, this
      did not translate into increased EI during a test meal. Given the increasing
      prevalence of shift workers and incidences of sleep disorders, additional studies
      are needed to evaluate the prolonged effects of voluntary sleep restriction with
      altered sleep timing on appetite and EI measurements.

PMID- 27866989
TI  - Do interoceptive awareness and interoceptive responsiveness mediate the
      relationship between body appreciation and intuitive eating in young women?
AB  - The extent to which an individual appreciates their own body is recognised as a
      proximal predictor of intuitive eating, but the mechanisms underlying this
      relationship are less clearly understood. This study tested whether two partially
      independent, self-reported facets of interoceptive ability: 'interoceptive
      awareness' (defined as the ability to detect internal bodily cues) and
      'interoceptive responsiveness' (the way in which individuals value and respond to
      these cues) mediated the relationship between body appreciation and three
      subscales of intuitive eating: 'unconditional permission to eat'; 'reliance on
      internal hunger and satiety cues', and 'eating for physical rather than emotional
      reasons'. Multiple mediation analyses of data from an online survey of Australian
      college women (n = 200) showed that: (1) interoceptive awareness partially
      mediated the relationship between body appreciation and 'reliance on internal
      hunger and satiety cues', and (2) interoceptive responsiveness partially mediated
      the relationship between all three subscales of intuitive eating. Although
      preliminary, this work lends support to the theoretical framework of the
      acceptance model of intuitive eating and extends it by suggesting that the
      different facets of intuitive eating may have distinct underlying mechanisms.

PMID- 27866990
TI  - Longitudinal auditory learning facilitates auditory cognition as revealed by
      microstate analysis.
AB  - The current study investigates cognitive processes as reflected in late auditory
      evoked potentials as a function of longitudinal auditory learning. A normal
      hearing adult sample (n=15) performed an active oddball task at three consecutive
      time points (TPs) arranged at two week intervals, and during which EEG was
      recorded. The stimuli comprised of syllables consisting of a natural fricative
      (/sh/,/s/,/f/) embedded between two /a/ sounds, as well as morphed transitions of
      the two syllables that served as deviants. Perceptual and cognitive modulations
      as reflected in the onset and the mean global field power (GFP) of N2b- and P3b
      related microstates across four weeks were investigated. We found that the onset
      of P3b-like microstates, but not N2b-like microstates decreased across TPs, more
      strongly for difficult deviants leading to similar onsets for difficult and easy
      stimuli after repeated exposure. The mean GFP of all N2b-like and P3b-like
      microstates increased more in spectrally strong deviants compared to weak
      deviants, leading to a distinctive activation for each stimulus after learning.
      Our results indicate that longitudinal training of auditory-related cognitive
      mechanisms such as stimulus categorization, attention and memory updating
      processes are an indispensable part of successful auditory learning. This
      suggests that future studies should focus on the potential benefits of cognitive
      processes in auditory training.

PMID- 27866991
TI  - Parkinson's disease-like motor and non-motor symptoms in rotenone-treated
      zebrafish.
AB  - The pesticide rotenone is widely used to produce Parkinson's disease (PD)-like
      symptoms in rodents, but few studies have examined whether rotenone-treated
      zebrafish can serve as an animal model of PD. Here, we report that 4 weeks of
      rotenone treatment induced motor and non-motor PD-like symptoms in adult
      zebrafish. Compared with control fish, rotenone-treated fish spent less time
      swimming at a fast speed, indicating a deficit in motor function. In the light
      dark box test, rotenone-treated fish exhibited longer latencies to enter the dark
      compartment and spent more time in the light compartment, reflecting anxiety- and
      depression-like behavior. Furthermore, rotenone-treated fish showed less of an
      olfactory preference for amino acid, indicating olfactory dysfunction. These
      behavioral symptoms were associated with decreased levels of dopamine in the
      brains of rotenone-treated fish. Taken together, these results suggest that
      rotenone-treated zebrafish are a suitable model of PD.

PMID- 27866992
TI  - Comorbidities That Cause Pain and the Contributors to Pain in Individuals With
      Chronic Obstructive Pulmonary Disease.
AB  - OBJECTIVE: To determine comorbidities that cause pain and the potential
      contributors to pain in individuals with chronic obstructive pulmonary disease
      (COPD). DESIGN: Prospective cross-sectional survey study. SETTING: Pulmonary
      rehabilitation programs of 6 centers. PARTICIPANTS: A convenience sample of
      individuals with COPD (N=137) who attended pulmonary rehabilitation programs. In
      total, 100 (73%) returned the survey packages. Of those responders, 96
      participants (70%) were included in the analyses. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Pain was measured using the Brief Pain Inventory. The
      questionnaire used to obtain information about health conditions that might
      contribute to pain and a medication record asked, in lay terms, about
      comorbidities that cause pain. The health conditions that cause pain were then
      validated by health professionals. Demographics, fatigue, dyspnea, quality of
      life, and self-efficacy were also measured using questionnaires. RESULTS: Pain
      was reported in 71% (68/96) of participants. Low back pain was the most common
      location (41%). Arthritis (75%), back problems (47%), and muscle cramps (46%)
      were the most common comorbidities that caused pain. Lower self-efficacy, and
      renting rather than home ownership increased the likelihood of pain (P<.05). Pain
      severity and Brief Fatigue Inventory scores contributed to pain interference
      scores (P<.05). CONCLUSIONS: Pain was highly prevalent in pulmonary
      rehabilitation program participants with COPD. The most common causes of pain
      were musculoskeletal conditions. Pain severity and higher levels of fatigue
      contributed to how pain interfered with daily aspects of living. The assessment
      and management of pain need to be addressed within the overall care of
      individuals with COPD.

PMID- 27866993
TI  - MicroRNAs 223-3p and 93-5p in patients with chronic kidney disease before and
      after renal transplantation.
AB  - Chronic kidney disease (CKD) is associated with a multifactorial dysregulation of
      bone and vascular calcification and closely linked to increased cardiovascular
      mortality and concomitant bone disease. We aimed to investigate specific microRNA
      (miRNA) signatures in CKD patients to find indicators for vascular calcification
      and/or bone mineralization changes during CKD and after kidney transplantation
      (KT). A miRNA array was used to investigate serum miRNA profiles in CKD patients,
      then selected miRNAs were quantified in a validation cohort comprising 73
      patients in CKD stages 3 to 5, 67 CKD patients after KT, and 36 healthy controls.
      A spectrum of biochemical parameters including markers for kidney function,
      inflammation, glucose, and mineral metabolism was determined. The relative
      expression of miR-223-3p and miR-93-5p was down-regulated in patients with CKD
      stage 4 and 5 compared to healthy controls. This down-regulation disappeared
      after kidney transplantation even when lower glomerular filtration rates (eGFR)
      persisted. MiR-223-3p and miR-93-5p were associated with interleukin-6 (IL-6) and
      eGFR levels, and by trend with interleukin-8 (IL-8), C-peptide, hematocrit, and
      parathyroid hormone (PTH). This study contributes new knowledge of serum miRNA
      expression profiles in CKD, potentially reflecting pathophysiological changes of
      bone and calcification pathways associated with inflammation, vascular
      calcification, mineral and glucose metabolism. Identified miRNA signatures can
      contribute to future risk markers or future therapeutic targets in bone and
      kidney disease.

PMID- 27866994
TI  - Corrigendum to genome-wide association study in East Asians suggests UHMK1 as a
      novel bone mineral density susceptibility gene.

PMID- 27866995
TI  - An integrated decision making approach for assessing healthcare waste treatment
      technologies from a multiple stakeholder.
AB  - With increased worldwide awareness of environmental issues, healthcare waste
      (HCW) management has received much attention from both researchers and
      practitioners over the past decade. The task of selecting the optimum treatment
      technology for HCWs is a challenging decision making problem involving
      conflicting evaluation criteria and multiple stakeholders. In this paper, we
      develop an integrated decision making framework based on cloud model and MABAC
      method for evaluating and selecting the best HCW treatment technology from a
      multiple stakeholder perspective. The introduced framework deals with uncertain
      linguistic assessments of alternatives by using interval 2-tuple linguistic
      variables, determines decision makers' relative weights based on the uncertainty
      and divergence degrees of every decision maker, and obtains the ranking of all
      HCW disposal alternatives with the aid of an extended MABAC method. Finally, an
      empirical example from Shanghai, China, is provided to illustrate the feasibility
      and effectiveness of the proposed approach. Results indicate that the methodology
      being proposed is more suitable and effective to handle the HCW treatment
      technology selection problem under vague and uncertain information environment.

PMID- 27866996
TI  - Spatial and temporal characteristics of elevated temperatures in municipal solid
      waste landfills.
AB  - Elevated temperatures in waste containment facilities can pose health,
      environmental, and safety risks because they generate toxic gases, pressures,
      leachate, and heat. In particular, MSW landfills undergo changes in behavior that
      typically follow a progression of indicators, e.g., elevated temperatures,
      changes in gas composition, elevated gas pressures, increased leachate migration,
      slope movement, and unusual and rapid surface settlement. This paper presents two
      MSW landfill case studies that show the spatial and time-lapse movements of these
      indicators and identify four zones that illustrate the transition of normal MSW
      decomposition to the region of elevated temperatures. The spatial zones are gas
      front, temperature front, and smoldering front. The gas wellhead temperature and
      the ratio of CH4 to CO2 are used to delineate the boundaries between normal MSW
      decomposition, gas front, and temperature front. The ratio of CH4 to CO2 and
      carbon monoxide concentrations along with settlement strain rates and subsurface
      temperatures are used to delineate the smoldering front. In addition, downhole
      temperatures can be used to estimate the rate of movement of elevated
      temperatures, which is important for isolating and containing the elevated
      temperature in a timely manner.

PMID- 27866997
TI  - Recovery of metallic concentrations from waste printed circuit boards via reverse
      floatation.
AB  - Efficient disposal of waste printed circuit boards (PCBs) is favorable toward
      recovering valuable components and reducing pollution. Reverse floatation was
      used to recover metallic concentrations from waste PCBs. Basic properties and
      mineralogical characteristics of raw PCBs were tested and analyzed. Results
      indicated that the grade of metallic concentrations declined as the size fraction
      of PCBs decreased. The major metallic elements found in PCBs were Cu, Pb, and Sn,
      as well as trace elements were also found in fine PCB particles. Kerosene and
      terpenic oil were used as the collector and frother in the floatation
      experiments. The effects of various operational factors, including the feeding
      concentration, aeration rate, and agitation speed of floatation machine, on the
      floatation performance of -0.25mm PCBs were experimentally studied to determine
      optimal range. The floatation results suggested that the yield of sinks and grade
      of metallic concentrations diminished significantly with the decrease of size
      fraction of PCBs. The maximum yields of sinks and highest grades of metallic
      concentrations were 48.72% and 16.86%, 47.96% and 14.61%, 44.36% and 8.81%, with
      the optimum recoveries of metallic concentrations of 94.69%, 90.06%, and 75.96%
      for size fractions of 0.125-0.25mm, 0.074-0.125mm, and -0.074mm PCBs,
      respectively. The recovery efficiency of metallic concentrations declined as the
      size fraction decreased. The efficient overall recovery performance of metallic
      concentrations from waste PCBs was obtained via reverse floatation. This study
      provides an alternative approach for disposing waste PCBs.

PMID- 27866998
TI  - Tomographic inversion of time-domain resistivity and chargeability data for the
      investigation of landfills using a priori information.
AB  - In this paper, we present a new code for the modelling and inversion of
      resistivity and chargeability data using a priori information to improve the
      accuracy of the reconstructed model for landfill. When a priori information is
      available in the study area, we can insert them by means of inequality
      constraints on the whole model or on a single layer or assigning weighting
      factors for enhancing anomalies elongated in the horizontal or vertical
      directions. However, when we have to face a multilayered scenario with numerous
      resistive to conductive transitions (the case of controlled landfills), the
      effective thickness of the layers can be biased. The presented code includes a
      model-tuning scheme, which is applied after the inversion of field data, where
      the inversion of the synthetic data is performed based on an initial guess, and
      the absolute difference between the field and synthetic inverted models is
      minimized. The reliability of the proposed approach has been supported in two
      real-world examples; we were able to identify an unauthorized landfill and to
      reconstruct the geometrical and physical layout of an old waste dump. The
      combined analysis of the resistivity and chargeability (normalised) models help
      us to remove ambiguity due to the presence of the waste mass. Nevertheless, the
      presence of certain layers can remain hidden without using a priori information,
      as demonstrated by a comparison of the constrained inversion with a standard
      inversion. The robustness of the above-cited method (using a priori information
      in combination with model tuning) has been validated with the cross-section from
      the construction plans, where the reconstructed model is in agreement with the
      original design.

PMID- 27866999
TI  - The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release
      in the prefrontal cortex and dopamine release in the nucleus accumbens and
      decreases motivation for reward and "waiting" impulsivity, but increases
      "stopping" impulsivity.
AB  - The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that
      resembles that of a variety of psychostimulant drugs, despite the differences in
      receptor binding profile. These psychostimulants are effective in treating
      impulsivity disorders, most likely because they increase norepinephrine (NE) and
      dopamine (DA) levels in the prefrontal cortex. Both amphetamine and
      methylphenidate, however, also increase dopamine levels in the nucleus accumbens
      (NAc), which has a significant role in motivation, pleasure, and reward. How
      eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the
      orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether
      eltoprazine affects different forms of impulsivity and brain reward mechanisms.
      Therefore, in the present study, we investigate the effects of eltoprazine in
      rats in the following sequence: 1) the activity of the monoaminergic systems
      using in vivo microdialysis, 2) motivation for reward measured using the
      intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting"
      impulsivity in the delay-aversion task, and the "stopping" impulsivity in the
      stop-signal task. The microdialysis studies clearly showed that eltoprazine
      increased DA and NE release in both the mPFC and OFC, but only increased DA
      concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the
      mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased
      impulsive choice, but increased impulsive action. Furthermore, brain stimulation
      was less rewarding following eltoprazine treatment. These results further support
      the long-standing hypothesis that "waiting" and "stopping" impulsivity are
      regulated by distinct neural circuits, because 5-HT1A/1B-receptor activation
      decreases impulsive choice, but increases impulsive action.

PMID- 27867000
TI  - Neuromodulatory effects of the dorsal hippocampal endocannabinoid system in
      dextromethorphan/morphine-induced amnesia.
AB  - Dextromethorphan which is an active ingredient in many cough medicines has been
      previously shown to potentiate amnesic effect of morphine in rats. However, the
      effect of dextromethorphan, that is also a noncompetitive N-methyl-D-aspartate
      (NMDA) receptor antagonist, in combination with morphine on hippocampus-based
      long term memory has not been well characterized. The aim of the present study
      was to assess the possible role of endocannabinoid system of the dorsal
      hippocampus in dextromethorphan /morphine-induced amnesia. Our results showed
      that intraperitoneal (i.p.) injection of morphine (5mg/kg) or dextromethorphan (5
      15mg/kg) before testing the passive avoidance learning induced amnesia.
      Combination of ineffective doses of dextromethorphan (7.5mg/kg, i.p.) and
      morphine (2mg/kg, i.p.) also produced amnesia, suggesting the enhancing effects
      of the drugs. To assess the effect of the activation or inhibition of the dorsal
      hippocampal cannabinoid CB1 receptors on this amnesia, ACPA or AM251 as selective
      receptor agonists or antagonists were respectively injected into the CA1 regions
      before systemic injection of dextromethorphan and morphine. Interestingly, intra
      CA1 microinjection of ACPA (0.5-1ng/rat) improved the amnesic effect of
      dextromethorphan /morphine combination. The microinjection of AM251 into the CA1
      region enhanced the response of the combination of dextromethorphan /morphine in
      inducing amnesia. Moreover, Intra-CA1 microinjection of AM251 inhibited the
      improving effect of ACPA on dextromethorphan /morphine-induced amnesia. It is
      important to note that intra-CA1 microinjection of the same doses of the agonist
      or antagonist by itself had no effects on memory formation. Thus, it can be
      concluded that the dorsal hippocampal endocannabinoid system, via CB1 receptor
      dependent mechanism, may be involved in morphine/dextromethorphan -induced
      amnesia.

PMID- 27867001
TI  - Comparison of Amrubicin and Weekly Cisplatin/Etoposide/Irinotecan in Patients
      With Relapsed Small-cell Lung Cancer.
AB  - BACKGROUND: Although several agents have been introduced for the treatment of
      relapsed small-cell lung cancer (SCLC), there is still only limited evidence
      regarding second- and later-line chemotherapies for these patients. PATIENTS AND
      METHODS: Consecutive patients with relapsed SCLC treated at the National Cancer
      Center Hospital between 2000 and 2014 were analyzed. Patients' characteristics
      and treatments to explore factors associated with the survival outcomes were
      reviewed. RESULTS: A total of 580 patients diagnosed as having SCLC received
      first-line chemotherapy/chemoradiotherapy, of which 343 (59%) received second
      line chemotherapy. Among the 343 patients, 193, 148, and 2 patients were
      diagnosed sensitive relapse, refractory relapse, and relapse of unknown
      sensitivity status, respectively. Second-line chemotherapy regimens used were as
      follows: amrubicin (AMR) in 188 (55%) patients; weekly
      cisplatin/etoposide/irinotecan (PEI) in 56 (16%) patients; topotecan in 18 (5.2%)
      patients; others in 81 (24%) patients. In the analysis including all patients,
      the following outcomes were obtained for the patients treated with AMR and PEI,
      respectively: objective response rate: 51% and 73%; median progression-free
      survival: 4.5 and 4.2 months; median overall survival: 10.0 and 10.8 months.
      Multivariate analysis identified sensitive relapse to first-line treatment (vs.
      refractory relapse) (P = .007) and AMR as second-line treatment (vs. PEI) (P =
      .005) as independent favorable prognostic factors for survival. CONCLUSION: AMR
      showed a favorable trend compared with PEI in terms of the progression-free
      survival and feasibility in SCLC patients with relapsed disease. Based on our
      findings, we suggest that a randomized trial comparing AMR and PEI is warranted.

PMID- 27867002
TI  - Trametinib plus 4-Methylumbelliferone Exhibits Antitumor Effects by ERK Blockade
      and CD44 Downregulation and Affects PD-1 and PD-L1 in Malignant Pleural
      Mesothelioma.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive
      malignancy in which the mitogen-activated protein kinase pathway plays a critical
      role in the regulation of tumorigenesis. Hyaluronic acid (HA) is a major
      component of the extracellular matrix, and elevated HA levels with a concurrent
      increase in malignant properties are associated with MPM. METHODS: We evaluated
      the effects of trametinib, a mitogen-activated protein kinase (MEK) inhibitor,
      and 4-methylumbelliferone (4-MU), an HA synthesis inhibitor, alone and in
      combination on MPM cells in vitro and in vivo. We studied the effects of
      trametinib, 4-MU, and their combination on MPM cells by using cell viability
      assays, Western blot analysis, and a mouse xenograft model. RESULTS: Trametinib
      and 4-MU exhibited antiproliferative activity in MPM cells. Trametinib blocked
      MEK-dependent extracellular signal-regulated kinase (ERK) phosphorylation and
      decreased CD44 expression in a concentration-dependent manner. Trametinib
      inhibited the expression of Fra-1 (the activator protein 1 [AP1] component),
      inhibited ERK phosphorylation, and decreased CD44 expression. 4-MU inhibited ERK
      phosphorylation but not CD44 expression. In a mouse xenograft model, trametinib
      and 4-MU alone suppressed tumor growth compared with a control. The combination
      had a greater inhibitory effect than either monotherapy. Immunohistochemical
      analysis showed that trametinib treatment alone significantly reduced expression
      of programmed cell death 1 ligand 1. Furthermore, the combination of trametinib
      and 4-MU resulted in higher expression of programmed cell death 1 and programmed
      cell death 1 ligand 1 than did the 4-MU treatment alone. CONCLUSIONS: Our results
      suggest that trametinib and 4-MU are promising therapeutic agents in MPM and that
      further study of the combination is warranted.

PMID- 27867003
TI  - Prognostic Impact of Newly Proposed M Descriptors in TNM Classification of Non
      Small Cell Lung Cancer.
AB  - INTRODUCTION: The International Association for the Study of Lung Cancer recently
      proposed new M descriptors for the next edition of the TNM classification for
      NSCLC, subdividing the current M1b category into two subcategories: M1b, which
      indicates a solitary extrathoracic metastasis in a single organ, and M1c, which
      indicates multiple extrathoracic metastasis. The purpose of this study was to
      validate the prognostic value of the newly proposed M descriptors in an
      independent cohort with multivariate and subgroup analysis. METHODS: A total of
      1024 patients in a consecutive lung cancer database who had stage IV NSCLC
      treated between 2011 and 2014 were analyzed. Newly proposed M staging was used
      for classification and comparison of survival. Adjustment for other clinical
      covariates and subgroup analysis was conducted. RESULTS: According to the newly
      proposed M descriptors, 262 patients (25.6%), 152 patients (14.8%), and 610
      patients (59.6%) were classified into the subgroups M1a, M1b, and M1c,
      respectively. The median overall survival times were 22.5, 17.8, and 13.6 months
      for the M1a, M1b, and M1c groups, respectively (p < 0.001). After adjustment for
      other covariates, Cox proportional hazards regression revealed statistically
      significantly shorter overall survival for the M1b group than for the M1a group
      (hazard ratio = 1.30; 95% confidence interval: 1.03-1.65, p = 0.03) and for the
      M1c than the M1b group (hazard ratio = 1.57; 95% confidence interval: 1.28-1.93,
      p < 0.001). These differences showed a consistent tendency regardless of
      pathologic and molecular subtypes. CONCLUSIONS: The newly proposed M descriptors
      have prognostic value in patients with stage IV NSCLC.

PMID- 27867004
TI  - Metabolic engineering of Bacillus subtilis fueled by systems biology: Recent
      advances and future directions.
AB  - By combining advanced omics technology and computational modeling, systems
      biologists have identified and inferred thousands of regulatory events and system
      wide interactions of the bacterium Bacillus subtilis, which is commonly used both
      in the laboratory and in industry. This dissection of the multiple layers of
      regulatory networks and their interactions has provided invaluable information
      for unraveling regulatory mechanisms and guiding metabolic engineering. In this
      review, we discuss recent advances in the systems biology and metabolic
      engineering of B. subtilis and highlight current gaps in our understanding of
      global metabolism and global pathway engineering in this organism. We also
      propose future perspectives in the systems biology of B. subtilis and suggest
      ways that this approach can be used to guide metabolic engineering. Specifically,
      although hundreds of regulatory events have been identified or inferred via
      systems biology approaches, systematic investigation of the functionality of
      these events in vivo has lagged, thereby preventing the elucidation of regulatory
      mechanisms and further rational pathway engineering. In metabolic engineering,
      ignoring the engineering of multilayer regulation hinders metabolic flux
      redistribution. Post-translational engineering, allosteric engineering, and
      dynamic pathway analyses and control will also contribute to the modulation and
      control of the metabolism of engineered B. subtilis, ultimately producing the
      desired cellular traits. We hope this review will aid metabolic engineers in
      making full use of available systems biology datasets and approaches for the
      design and perfection of microbial cell factories through global metabolism
      optimization.

PMID- 27867006
TI  - Intercellular Coupling of the Cell Cycle and Circadian Clock in Adult Stem Cell
      Culture.
AB  - Circadian clock-gated cell division cycles are observed from cyanobacteria to
      mammals via intracellular molecular connections between these two oscillators.
      Here we demonstrate WNT-mediated intercellular coupling between the cell cycle
      and circadian clock in 3D murine intestinal organoids (enteroids). The circadian
      clock gates a population of cells with heterogeneous cell-cycle times that emerge
      as 12-hr synchronized cell division cycles. Remarkably, we observe reduced
      amplitude oscillations of circadian rhythms in intestinal stem cells and
      progenitor cells, indicating an intercellular signal arising from differentiated
      cells governing circadian clock-dependent synchronized cell division cycles.
      Stochastic simulations and experimental validations reveal Paneth cell-secreted
      WNT as the key intercellular coupling component linking the circadian clock and
      cell cycle in enteroids.

PMID- 27867005
TI  - Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early
      developmental stages of human retinal ganglion cells in embryonic stem cell
      derived retina.
AB  - Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs)
      have anticipated value for human disease study, drug screening, and therapeutic
      applications; however, their full potential remains underdeveloped. To
      characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids
      we examined RGC markers and surface antigen expression and made comparisons to
      human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and
      distinct expression patterns of the RGC markers BRN3 and RBPMS. The retinal
      progenitor cells (RPCs) of retinal organoids expressed CD184, consistent with its
      expression in the neuroblastic layer in fetal retina. In retinal organoids CD184
      expression was enhanced in RGC competent RPCs and high CD184 expression was
      retained on post-mitotic RGC precursors; CD171 was detected on maturing RGCs. The
      differential expression timing of CD184 and CD171 permits identification and
      enrichment of RGCs from retinal organoids at differing maturation states from
      committed progenitors to differentiating neurons. These observations will
      facilitate molecular characterization of PSC-derived RGCs during differentiation,
      critical knowledge for establishing the veracity of these in vitro produced
      cells. Furthermore, observations made in the retinal organoid model closely
      parallel those in human fetal retina further validating use of retinal organoid
      to model early retinal development.

PMID- 27867007
TI  - SRF Co-factors Control the Balance between Cell Proliferation and Contractility.
AB  - The ERK-regulated ternary complex factors (TCFs) act with the transcription
      factor serum response factor (SRF) to activate mitogen-induced transcription.
      However, the extent of their involvement in the immediate-early transcriptional
      response, and their wider functional significance, has remained unclear. We show
      that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible
      gene transcription and impairs cell proliferation. Using integrated SRF ChIP-seq
      and Hi-C data, we identified over 700 TCF-dependent SRF direct target genes
      involved in signaling, transcription, and proliferation. These also include a
      significant number of cytoskeletal gene targets for the Rho-regulated myocardin
      related transcription factor (MRTF) SRF cofactor family. The TCFs act as general
      antagonists of MRTF-dependent SRF target gene expression, competing directly with
      the MRTFs for access to SRF. As a result, TCF-deficient MEFs exhibit
      hypercontractile and pro-invasive behavior. Thus, competition between TCFs and
      MRTFs for SRF determines the balance between antagonistic proliferative and
      contractile programs of gene expression.

PMID- 27867008
TI  - Molecular Structures of Transcribing RNA Polymerase I.
AB  - RNA polymerase I (Pol I) is a 14-subunit enzyme that solely synthesizes pre
      ribosomal RNA. Recently, the crystal structure of apo Pol I gave unprecedented
      insight into its molecular architecture. Here, we present three cryo-EM
      structures of elongating Pol I, two at 4.0 A and one at 4.6 A resolution, and a
      Pol I open complex at 3.8 A resolution. Two modules in Pol I mediate the
      narrowing of the DNA-binding cleft by closing the clamp domain. The DNA is bound
      by the clamp head and by the protrusion domain, allowing visualization of the
      upstream and downstream DNA duplexes in one of the elongation complexes. During
      formation of the Pol I elongation complex, the bridge helix progressively folds,
      while the A12.2 C-terminal domain is displaced from the active site. Our results
      reveal the conformational changes associated with elongation complex formation
      and provide additional insight into the Pol I transcription cycle.

PMID- 27867009
TI  - A Polar and Nucleotide-Dependent Mechanism of Action for RAD51 Paralogs in RAD51
      Filament Remodeling.
AB  - Central to homologous recombination in eukaryotes is the RAD51 recombinase, which
      forms helical nucleoprotein filaments on single-stranded DNA (ssDNA) and
      catalyzes strand invasion with homologous duplex DNA. Various regulatory proteins
      assist this reaction including the RAD51 paralogs. We recently discovered that a
      RAD51 paralog complex from C. elegans, RFS-1/RIP-1, functions predominantly
      downstream of filament assembly by binding and remodeling RAD-51-ssDNA filaments
      to a conformation more proficient for strand exchange. Here, we demonstrate that
      RFS-1/RIP-1 acts by shutting down RAD-51 dissociation from ssDNA. Using stopped
      flow experiments, we show that RFS-1/RIP-1 confers this dramatic stabilization by
      capping the 5' end of RAD-51-ssDNA filaments. Filament end capping propagates a
      stabilizing effect with a 5'->3' polarity approximately 40 nucleotides along
      individual filaments. Finally, we discover that filament capping and
      stabilization are dependent on nucleotide binding, but not hydrolysis by RFS
      1/RIP-1. These data define the mechanism of RAD51 filament remodeling by RAD51
      paralogs.

PMID- 27867010
TI  - Quorum Sensing Controls Adaptive Immunity through the Regulation of Multiple
      CRISPR-Cas Systems.
AB  - Bacteria commonly exist in high cell density populations, making them prone to
      viral predation and horizontal gene transfer (HGT) through transformation and
      conjugation. To combat these invaders, bacteria possess an arsenal of defenses,
      such as CRISPR-Cas adaptive immunity. Many bacterial populations coordinate their
      behavior as cell density increases, using quorum sensing (QS) signaling. In this
      study, we demonstrate that QS regulation results in increased expression of the
      type I-E, I-F, and III-A CRISPR-Cas systems in Serratia cells in high-density
      populations. Strains unable to communicate via QS were less effective at
      defending against invaders targeted by any of the three CRISPR-Cas systems.
      Additionally, the acquisition of immunity by the type I-E and I-F systems was
      impaired in the absence of QS signaling. We propose that bacteria can use
      chemical communication to modulate the balance between community-level defense
      requirements in high cell density populations and host fitness costs of basal
      CRISPR-Cas activity.

PMID- 27867013
TI  - Characterization of P2X4 receptor agonists and antagonists by calcium influx and
      radioligand binding studies.
AB  - Antagonists for ATP-activated P2X4 ion channel receptors are currently in the
      focus as novel drug targets, in particular for the treatment of neuropathic and
      inflammatory pain. We stably expressed the human, rat and mouse P2X4 receptors in
      1321N1 astrocytoma cells, which is devoid of functional nucleotide receptors, by
      retroviral transfection, and established monoclonal cell lines. Calcium flux
      assay conditions were optimized for high-throughput screening resulting in a Z'
      factor of >0.8. The application of ready-to-use frozen cells did not negatively
      affect the results of the calcium assays, which is of great advantage for the
      screening of compound libraries. Species differences were observed, the rat P2X4
      receptor being particularly insensitive to many ATP derivatives. Membrane
      preparations of the cell lines showed high levels of specific [35S]ATPgammaS
      binding with low nonspecific binding (<5% of total binding), while non
      transfected cells were devoid of specific binding sites for the radioligand.
      Conditions were employed which allow binding studies to be performed at room
      temperature. While a variety of nucleotide-derived agonists and the antagonist
      TNP-ATP displaced [35S]ATPgammaS from its binding site at human P2X4 receptors,
      the non-nucleotidic antagonists paroxetine and 5-BDBD did not compete with
      radioligand binding and were therefore characterized as allosteric antagonists.
      Homology modeling was applied to find an explanation for the observed species
      differences.

PMID- 27867012
TI  - A robust sparse-modeling framework for estimating schizophrenia biomarkers from
      fMRI.
AB  - BACKGROUND: Our goal is to identify the brain regions most relevant to mental
      illness using neuroimaging. State of the art machine learning methods commonly
      suffer from repeatability difficulties in this application, particularly when
      using large and heterogeneous populations for samples. NEW METHOD: We revisit
      both dimensionality reduction and sparse modeling, and recast them in a common
      optimization-based framework. This allows us to combine the benefits of both
      types of methods in an approach which we call unambiguous components. We use this
      to estimate the image component with a constrained variability, which is best
      correlated with the unknown disease mechanism. RESULTS: We apply the method to
      the estimation of neuroimaging biomarkers for schizophrenia, using task fMRI data
      from a large multi-site study. The proposed approach yields an improvement in
      both robustness of the estimate and classification accuracy. COMPARISON WITH
      EXISTING METHODS: We find that unambiguous components incorporate roughly two
      thirds of the same brain regions as sparsity-based methods LASSO and elastic net,
      while roughly one third of the selected regions differ. Further, unambiguous
      components achieve superior classification accuracy in differentiating cases from
      controls. CONCLUSIONS: Unambiguous components provide a robust way to estimate
      important regions of imaging data.

PMID- 27867011
TI  - Tetrameric Acetyl-CoA Acetyltransferase 1 Is Important for Tumor Growth.
AB  - Mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1) regulates pyruvate
      dehydrogenase complex (PDC) by acetylating pyruvate dehydrogenase (PDH) and PDH
      phosphatase. How ACAT1 is "hijacked" to contribute to the Warburg effect in human
      cancer remains unclear. We found that active, tetrameric ACAT1 is commonly
      upregulated in cells stimulated by EGF and in diverse human cancer cells, where
      ACAT1 tetramers, but not monomers, are phosphorylated and stabilized by enhanced
      Y407 phosphorylation. Moreover, we identified arecoline hydrobromide (AH) as a
      covalent ACAT1 inhibitor that binds to and disrupts only ACAT1 tetramers. The
      resultant AH-bound ACAT1 monomers cannot reform tetramers. Inhibition of
      tetrameric ACAT1 by abolishing Y407 phosphorylation or AH treatment results in
      decreased ACAT1 activity, leading to increased PDC flux and oxidative
      phosphorylation with attenuated cancer cell proliferation and tumor growth. These
      findings provide a mechanistic understanding of how oncogenic events signal
      through distinct acetyltransferases to regulate cancer metabolism and suggest
      ACAT1 as an anti-cancer target.

PMID- 27867014
TI  - The cave microbiome as a source for drug discovery: Reality or pipe dream?
AB  - This review highlights cave habitats, cave microbiomes and their potential for
      drug discovery. Such studies face many challenges, including access to remote and
      pristine caves, and sample collection and transport. Inappropriate physical and
      chemical growth conditions in the laboratory for the isolation and cultivation of
      cave microorganisms pose many complications including length of cultivation; some
      cave microorganisms can take weeks and even months to grow. Additionally, DNA
      extraction from cave environmental samples may be difficult due to the high
      concentration of various minerals that are natural DNA blocking agents. Once cave
      microorganisms are grown in the lab, other problems often arise, such as
      maintenance of pure culture, consistency of antimicrobial activity and
      fermentation conditions for antimicrobial production. In this review, we suggest
      that, although based on what has been done in the field, there is potential in
      using cave microorganisms to produce antimicrobial agents, one needs to be highly
      committed and prepared.

PMID- 27867015
TI  - CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5
      activity in gastric cancer.
AB  - CMTM3 (CKLF-like MARVEL transmembrane domain containing 3), a tumor suppressor
      gene, is involved in multiple types of malignancies. CMTM3 knockdown promotes
      metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway. Strong
      epidermal growth factor receptor1 (EGFR) expression is significantly associated
      with tumor metastasis and poor outcomes of gastric cancer patients. In this
      paper, we show that CMTM3 suppresses epidermal growth factor (EGF)-mediated
      migration and STAT3 signaling, downregulates EGFR expression via accelerating
      EGFR degradation in gastric cancer cells. CMTM3 colocalizes with early endosome
      markers Rab5 and EEA1. Co-immunoprecipitation (Co-IP) assay further confirms that
      CMTM3 interacts with Rab5. More importantly, CMTM3 markedly increases Rab5
      activity. The suppressive effects of CMTM3 on EGFR expression and EGF-mediated
      migration can be abrogated by the siRNA against Rab5. Finally, we found that the
      C-terminal region of CMTM3 plays more important roles in the tumor suppressive
      effects of CMTM3. Overall, this study demonstrates that CMTM3 decreases EGFR
      expression, facilitates EGFR degradation, and inhibits the EGF-mediated
      tumorigenicity of gastric cancer cells via enhancing Rab5 activity.

PMID- 27867016
TI  - Vasohibin 2 promotes epithelial-mesenchymal transition in human breast cancer via
      activation of transforming growth factor beta 1 and hypoxia dependent repression
      of GATA-binding factor 3.
AB  - Vasohibin 2 (VASH2) is identified as an angiogenic factor, and has been
      implicated in tumor angiogenesis, proliferation and epithelial-mesenchymal
      transition (EMT). To investigate the EMT role of VASH2 in breast cancer, we
      overexpressed or knocked down expression of VASH2 in human breast cancer cell
      lines. We observed that VASH2 induced EMT in vitro and in vivo. The transforming
      growth factor beta1 (TGFbeta1) pathway was activated by VASH2, and expression of
      a dominant negative TGFbeta type II receptor could block VASH2-mediated EMT. In
      clinical breast cancer tissues VASH2 positively correlated with TGFbeta1
      expression, but negatively correlated with E-cadherin (a marker of EMT)
      expression. Under hypoxic conditions in vitro or in vivo, we found that down
      regulation of estrogen receptor 1 (ESR1) in VASH2 overexpressing ESR1 positive
      cells suppressed E-cadherin. Correlation coefficient analysis indicated that
      VASH2 and ESR1 expression were negatively correlated in clinical human breast
      cancer tissues. Further study revealed that a transcription factor of ESR1, GATA
      binding factor 3 (GATA3), was down-regulated by VASH2 under hypoxia or in vivo.
      These findings suggest that VASH2 drives breast cancer cells to undergo EMT by
      activation of the TGFbeta1 pathway and hypoxia dependent repression GATA3-ESR1
      pathway, leading to cancer metastasis.

PMID- 27867018
TI  - Chitin synthase 1 gene is crucial to antifungal host defense of the model beetle,
      Tribolium castaneum.
AB  - The importance of the insect cuticle as a primary protective barrier against
      entomopathogens has long been noted. In the present study, we addressed this
      issue by utilizing an experimental infection system composed of the model beetle
      T. castaneum and two entomopathogenic fungal species, Beauveria bassiana and
      Metarhizium anisopliae. The pupae were relatively susceptible to these fungi by
      the natural route of infection, with some refractoriness developed with age,
      while the adults exhibited much higher refractoriness. Whereas M. anisopliae
      exhibited seemingly higher infectivity to the pupae compared to B. bassiana when
      the natural conidium infection was employed, direct inoculation of cultured
      hyphal body cells into the hemocoel was found highly and equally virulent in the
      pupae for the both fungal species. These results collectively suggest an
      important role of the cuticular integument in antifungal host defense, and we
      subsequently conducted the knockdown of chitin synthase 1 gene (CHS1). We
      targeted the prepupal and mid-pupal peaks of its expression respectively by using
      injection of the dsRNA at very low dosages to avoid lethality. The resulting
      pupae looked normal, but the adults showed a mild phenotype with dimpled/wrinkled
      elytra. The CHS1 gene knockdown compromised significantly host defense against
      the fungal infection via the natural route, except the configuration of knockdown
      pupae and M. anisopliae, suggesting an indispensable role of CHS1.

PMID- 27867019
TI  - Potential of RNAi applications to control viral diseases of farmed shrimp.
AB  - Viral pathogens pose a primary threat to global shrimp aquaculture. Despite the
      urgent industry need for them, practical anti-viral control methods are
      unavailable due, in part, to lack of an adaptive immune response in crustaceans
      that renders conventional vaccination methods ineffective. One currently studied
      method of high interest for protecting shrimp against viral infection relies on
      the post-transcriptional gene silencing mechanism called RNA interference (RNAi)
      that is induced by gene-specific constructs of double stranded RNA (dsRNA).
      Although this approach was first described for successful protection of shrimp
      against white spot disease (WSD) by injecting dsRNA specific to genes of white
      spot syndrome virus (WSSV) into shrimp in the laboratory in 2005 no practical
      method for use of dsRNA in shrimp farms has been developed to date. The apparent
      bottleneck for farm-scale applications of RNAi-mediated viral control in shrimp
      aquaculture is the lack of simple and cost-effective delivery methods. This
      review summarizes recent studies on use and delivery of dsRNA to shrimp via
      injection and oral routes in hatcheries and on farms and it discusses the
      research directions that might lead to development of practical methods for
      applications with farmed shrimp. Oral delivery methods tested so far include use
      of dsRNA-expressing bacteria as a component of dry feed pellets or use of living
      brine shrimp (Artemia) pre-fed with dsRNA before they are fed to shrimp. Also
      tested have been dsRNA enclosed in nanocontainers including chitosan, liposomes
      and viral-like particles (VLP) before direct injection or use as components of
      feed pellets for hatchery or pond-reared shrimp.

PMID- 27867017
TI  - Genomic amplification of Fanconi anemia complementation group A (FancA) in head
      and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance
      and clinical relevance.
AB  - Radio (chemo) therapy is a crucial treatment modality for head and neck squamous
      cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms
      remain largely elusive. Therefore, novel biomarkers are urgently needed.
      Previously, we identified gains on 16q23-24 to be associated with amplification
      of the Fanconi anemia A (FancA) gene and to correlate with reduced progression
      free survival after radiotherapy. Here, we analyzed the effects of FancA on
      radiation sensitivity in vitro, characterized the underlying mechanisms, and
      evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell
      lines with genomic gains on 16q23-24 resulted in significantly impaired
      clonogenic survival upon irradiation. Conversely, overexpression of FancA in
      immortalized keratinocytes conferred increased survival accompanied by improved
      DNA repair, reduced accumulation of chromosomal translocations, but no
      hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as
      identified by microarray analyses, enforced irradiation-induced senescence, and
      elevated production of the senescence-associated secretory phenotype (SASP)
      appeared to be candidate mechanisms contributing to FancA-mediated
      radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains
      on 16q24.3 with FancA overexpression and impaired overall survival. Importantly,
      transcriptomic alterations similar to those observed upon FancA overexpression in
      vitro strengthened the clinical relevance. Overall, FancA amplification and
      overexpression appear to be crucial for radiotherapeutic failure in HNSCC.

PMID- 27867020
TI  - A Randomized Dose Escalation Study of Intravenous Baclofen in Healthy Volunteers:
      Clinical Tolerance and Pharmacokinetics.
AB  - BACKGROUND: Abrupt discontinuation of baclofen can result in a potentially severe
      withdrawal syndrome. The current treatment for baclofen withdrawal is inadequate,
      resulting in a critical need to develop an alternative method to prevent or treat
      this withdrawal syndrome. OBJECTIVE: To evaluate the safety profile and
      pharmacokinetics of oral (PO) and investigational intravenous (IV) baclofen
      formulations at clinically relevant doses. DESIGN: Randomized, open-label, dose
      escalation, crossover study. SETTING: Contract Research Organization (CRO).
      METHODS: Three cohorts of 12 healthy adults received single doses of PO baclofen
      (10 mg, 15 mg or 20 mg) and 10-minute infusions of IV baclofen (7.5 mg, 11.5 mg,
      or 15 mg) with a minimum 48-hour wash-out period. The third cohort also received
      a 60-minute infusion of 15 mg IV baclofen after an additional 48-hour wash-out
      period. MAIN OUTCOME MEASURES: Subjects were observed in a CRO for 24 hours after
      each dose of baclofen, and were assessed for nystagmus, ataxia, and sedation.
      Blood samples were collected from 0 to 24 hours and analyzed for baclofen
      concentration using high-performance liquid chromatography-mass spectroscopy.
      Noncompartmental pharmacokinetic analyses were performed. Dose linearity and
      proportionality was assessed using 2-way repeated-measures analysis of variance
      and a power model analysis. RESULTS: None of the PO or IV doses resulted in
      significant sedation compared to baseline. All subjects could perform tandem gait
      after each baclofen dose. The most common side effect, transient mild nystagmus,
      was noted in 4 of 36 and in 13 of 36 subjects after PO and IV administration,
      respectively. This was likely related to increased maximum concentrations (Cmax).
      After the 20 mg PO and 15 mg IV doses, mean Cmax levels were 255 and 722 ng/mL
      and half-lives were 5.24 and 5.79 hours for PO and IV baclofen, respectively. The
      mean oral bioavailability for the 20-mg PO dose was approximately 80%.
      CONCLUSIONS: All PO and IV doses of baclofen were well tolerated clinically. The
      80% bioavailability suggests that a 20% reduction in IV dose will produce
      comparable total drug exposures to that of the PO dose. When PO therapy is
      interrupted, bridging with IV baclofen may be feasible. LEVEL OF EVIDENCE: II.

PMID- 27867022
TI  - Choroidal neovascularization secondary to Best vitelliform macular dystrophy
      detected by optical coherence tomography angiography.
AB  - Best vitelliform macular dystrophy (VMD) is a hereditary condition that causes
      childhood-onset macular dystrophy. In rare cases, VMD is accompanied by formation
      of a choroidal neovascular membrane (CNVM). We report a case of CNVM secondary to
      Best VMD in a 10-year-old boy that was detected using optical coherence
      tomography angiography, a new noninvasive diagnostic modality that detects motion
      contrast in repeated B-scans to identify blood flow within vessels.

PMID- 27867021
TI  - Patient-reported long-term sexual outcomes following plication surgery for penile
      curvature: A retrospective 58-patient study.
AB  - OBJECTIVE: To evaluate long-term sexual function results following plication
      surgery for the correction of penile curvature using patient questionnaires.
      METHODS: We performed a single-center, retrospective study in a cohort of
      patients with Peyronie's disease or congenital penile curvature. All patients who
      underwent plication surgery on the convex aspect using the Nesbit, Yachia or
      diamond-shaped techniques were included. At a mean 34 months after the
      interventions, the patients were asked to respond to the IIEF5 questionnaire and
      a 19-item questionnaire. RESULTS: Forty-six patients operated for Peyronie's
      disease and 12 for congenital curvature (total: 58) were included in the study.
      The questionnaire response rate was 69% (40/58). The shortened penis bothered
      47.5% of patients in their sexuality at least regularly. Involuntary exit from
      the vagina occurred for 35% of the patients in at least one out of two sexual
      intercourse sessions. Postoperative sexual life was as good as or better than
      preoperative sexual life for 35% of the patients and 95% stated that they could
      achieve erection at least sometimes, in coherence with the mean IIEF5 result of
      19.3/25. CONCLUSION: Our study suggests that even when successful, a relatively
      high rate of patients may be unsatisfied with the results of plication surgery,
      and there may be a relatively low rate of maintenance or improvement of
      postoperative sexual life. Furthermore, our in-house questionnaire, although not
      validated, shed light on how bothersome the loss of penis length is in
      postoperative sexuality, an aspect the IIEF5 and its sole evaluation of erectile
      quality cannot detect. LEVEL OF EVIDENCE: 4.

PMID- 27867024
TI  - Bariatric surgery in morbidly obese adolescents.

PMID- 27867023
TI  - The role of white matter microstructure in inhibitory deficits in patients with
      schizophrenia.
AB  - BACKGROUND: Inhibitory-excitatory (I-E) imbalance has increasingly been proposed
      as a fundamental mechanism giving rise to many schizophrenia-related
      pathophysiology. The integrity of I-E functions should require precise and rapid
      electrical signal transmission. OBJECTIVE/HYPOTHESIS: We hypothesized that part
      of the I-E abnormality in schizophrenia may originate from their known abnormal
      white matter connectivity that may interfere the I-E functions. METHODS: We test
      this using short-interval intracortical inhibition (SICI) vs. intracortical
      facilitation (ICF) which is a non-invasive measurement of I-E signaling. SICI-ICF
      from left motor cortex and white matter microstructure were assessed in
      schizophrenia patients and healthy controls. RESULTS: Schizophrenia patients
      showed significantly reduced SICI but not ICF. White matter microstructure as
      measured by fraction anisotropy (FA) in diffusion tensor imaging had a
      significant effect on SICI in patients, such that weaker SICI was associated with
      lower FA in several white matter tracts, most strongly with left corona radiata
      (r = -0.68, p = 0.0002) that contains the fibers connecting with left motor
      cortex. Left corticospinal tract, which carries the motor fibers to peripheral
      muscular output, also showed significant correlation with SICI (r = -0.54, p =
      0.005). Mediation analysis revealed that much of the schizophrenia disease effect
      on SICI can be accounted for by mediation through left corona radiata. SICI was
      also significantly associated with the performance of processing speed in
      patients. CONCLUSION: This study demonstrated the importance of structural
      circuitry integrity in inhibitory signaling in schizophrenia, and encouraged
      modeling the I-E dysfunction in schizophrenia from a circuitry perspective.

PMID- 27867025
TI  - Comparison of short-segment pedicle fixation with versus without inclusion of the
      fracture level in the treatment of mild thoracolumbar burst fractures.
AB  - BACKGROUND: A review of the literature showed that posterior short-segment
      fixation including the fractured vertebra (PSFFV) has better outcomes in the
      treatment of thoracolumbar burst fractures(TBFs) than patients with short-segment
      pedicle screw fixation(SSPF) alone. However, its efficacy in mild TBFs with load
      sharing scores of 3 and 4 points has not been specifically analyzed. The aim of
      this study was to compare the clinical, functional and radiologic results of
      PSFFV with SSPF for mild TBFs and to determine whether the screws in the
      fractured vetebra were necessary for these patients. METHODS: In this
      retrospective study, sixty-nine patients with mild TBFs were divided into 2
      groups according to the number of instrumented levels. Group A included 34
      patients treated by SSPF (four screws:one level above and below the fracture),
      and Group B included 35 patients treated by PSFFV (six screws: including the
      fractured vertebra). Clinical and radiologic parameters were evaluated before
      surgery, after surgery, and at follow-up. They included clinical outcomes: visual
      analog scale (VAS), Oswestry Disability Index (ODI). Being a radiology-based
      study, the radiologic measures included vertebral wedge angle (VWA), and anterior
      vertebral height (AVH). RESULTS: A sum of 69 patients (34 patients in Group A and
      35 patients in Group B) were enrolled in the study. The patients in both the
      groups showed similar outcomes with regards to age, gender, fracture type and
      site. We did not find any statistically difference between the two groups in
      corrected rate of VWA or AVH (P > 0.05). In terms of clinical variants such as
      VAS and ODI scores, there were also no significant differences. However, the SSPF
      had advantages over PSFFV method in operative time, blood loss, postoperative
      drainage and postoperative hospitalization time (P > 0.05). There were no serious
      complications occurring during our study, such as infection, blood vessel injury,
      spinal cord or nerve root injury. No patient needed revision for loss of
      correction or failure of instrumentation. CONCLUSIONS: SSPF alone is a safe and
      effective surgical method for restoration and maintenance of vertebral column
      stability in treating mild TBFs. It gives excellent clinical and radiological
      results regardless of whether the fractured vertebra is included in the fixation
      or not.

PMID- 27867027
TI  - Therapeutic potential of hepcidin - the master regulator of iron metabolism.
AB  - Iron is an essential biogenic element for both prokaryotic and eukaryotic cells.
      In humans iron is present in hundreds of different metalloproteins. The peptide
      hormone hepcidin serves as a master regulator of iron homeostasis on the level of
      single cells and whole organism - by altering cell surface expression of cellular
      iron exporter - protein ferroportin. Altered levels of extracellular hepcidin
      lead to pathological conditions such as hemochromatosis and iron loading or, on
      the other side, iron restrictive anemias. Therapeutic modulation of hepcidin is a
      new and promising approach to treatment of these conditions. In this review, a
      summary of the current knowledge of hepcidin function, regulation and
      pathological involvements are provided, followed by a section covering the
      therapeutic potential of hepcidin and the current strategies how to modulate its
      levels and biological functions for therapeutic purposes.

PMID- 27867029
TI  - Genotypic diversity of porcine circovirus type 2 (PCV2) and genotype shift to
      PCV2d in Korean pig population.
AB  - Porcine circovirus type 2 (PCV2) is a causative agent of PCV2-associated disease
      (PCVAD), which leads to enormous economic losses in the swine industry worldwide.
      A high nucleotide substitution rate allows for the continuous evolution of PCV2
      and the emergence of novel PCV2 strains. However, the distribution of emerging
      PCV2 genotypes and the co-existence of multiple genotypes in Korea have not been
      elucidated. The objective of this study was to determine the genetic diversity of
      PCV2 in Korean pig herds between 2009 and 2016. The overall prevalence of PCV2,
      from various samples originating from commercial pigs, was 53.8% (325/604). Two
      cases of a genotype shift to PCV2d at the farm level showed that the genotype
      shift started before 2012. In addition, genotype-specific PCR, on pen-based oral
      fluid samples for nationwide PCV2 surveillance in 2016, indicated that the
      infection pattern of PCV2 genotypes at the farm level was as follows; none
      (6/69), PCV2a (6/69), PCV2b (2/69), PCV2d (33/69), PCV2a/b (2/69), PCV2a/d
      (4/69), PCV2b/d (11/69), and PCV2a/b/d (2/69), respectively. This suggests that
      the genotype shift to PCV2d occurred on a nationwide scale and that the co
      existence of different genotypes is common in Korean pig herds. In addition,
      seven sites on the capsid protein of Korean PCV2 were identified as being under
      positive selection pressure, all of which are related to the epitope region and
      neutralization activity. These data provide evidence of increased genetic
      diversity and shifts among Korean PCV2 isolates.

PMID- 27867026
TI  - Artemisinin and its derivatives in treating protozoan infections beyond malaria.
AB  - Parasitic protozoan diseases continue to rank among the world's greatest global
      health problems, which are also common among poor populations. Currently
      available drugs for treatment present drawbacks, urging the need for more
      effective, safer, and cheaper drugs. Artemisinin (ART) and its derivatives are
      some of the most important classes of antimalarial agents originally derived from
      Artemisia annua L. However, besides the outstanding antimalarial and
      antischistosomal activities, ART and its derivatives also possess activities
      against other parasitic protozoa. In this paper we review the activities of ART
      and its derivatives against protozoan parasites in vitro and in vivo, including
      Leishmania spp., Trypanosoma spp., Toxoplasma gondii, Neospora caninum, Eimeria
      tenella, Acanthamoeba castellanii, Naegleria fowleri, Cryptosporidium parvum,
      Giardia lamblia, and Babesia spp. We conclude that ART and its derivatives may be
      good alternatives for treating other non-malarial protozoan infections in
      developing countries, although more studies are necessary before they can be
      applied clinically.

PMID- 27867030
TI  - Gemcitabine treatment enhanced the anti-tumor effect of cytokine induced killer
      cells by depletion of CD4+CD25bri regulatory T cells.
AB  - Cytokine induced killer (CIK) cells have a powerful tumor cells killing activity
      both in vitro and in vivo and transfusion of these cells have become an adjuvant
      treatment for tumors. CIK cells are induced and amplified from peripheral blood
      mononuclear cells (PBMCs) with multiple cytokines. As CD4+CD25bri regulatory T
      cells can be also induced by high dose of interleukin 2 (IL-2) which is used for
      CIK cells amplification in the CIK cell culture system, the anti-tumor activity
      of CIK cells was suppressed to some extent. In order to overcome this unwanted
      suppressive factor, we found that low dose of gemcitabine could reduce the
      proportion of CD4+CD25bri regulatory T cells in the CIK cell culture system and
      significantly enhance the anti-tumor activity of CIK cells in vitro. The levels
      of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) were
      also reduced significantly following the depletion of CD4+CD25bri regulatory T
      cells in gemcitabine treated CIK cell culture system. In vivo experiment showed
      that low dose of gemcitabine treated CIK cells significantly suppressed tumor
      growth and prolonged their lifespan in tumor-bearing nude mice, with the
      proportion of CD4+CD25bri regulatory T cells reduced. Meanwhile, we detected
      lower levels of IL-10, TGF-beta and a higher level of interferon-gamma (IFN
      gamma) in tumor-bearing nude mice that received gemcitabine treated CIK cells
      transfusion than those in other groups. The possible mechanism involved in the
      enhanced anti-tumor activity in vivo was that gemcitabine treated CIK cells
      created a strengthened anti-tumor immune microenvironment with the changed levels
      of cytokines such as IL-10, TGF-beta and IFN-gamma. These results suggested a
      strategy to improve the adoptive immune therapy in recent use by removing the
      suppressive factors and a more effective tumor treatment combining chemotherapy
      and immunotherapy.

PMID- 27867028
TI  - Control of human papillomavirus gene expression by alternative splicing.
AB  - Human papillomaviruses possess circular double stranded DNA genomes of around 8kb
      in size from which multiple mRNAs are synthesized during an infectious life
      cycle. Although at least three viral promoters are used to initiate
      transcription, viral mRNAs are largely the product of processing of pre-mRNAs by
      alternative splicing and polyadenylation. The HPV life cycle and viral gene
      expression are tightly linked to differentiation of the epithelium the virus
      infects: there is an orchestrated production of viral mRNAs and proteins. In this
      review we describe viral mRNA expression and the roles of the SR and hnRNP
      proteins that respectively positively and negatively regulate splicing. We
      discuss HPV regulation of splicing factors and detail the evidence that the
      papillomavirus E2 protein has splicing-related activities. We highlight the
      possibility that HPV-mediated control of splicing in differentiating epithelial
      cells may be necessary to accomplish the viral replication cycle.

PMID- 27867031
TI  - Marine n-3 fatty acids are incorporated into atrial tissue but do not correlate
      with postoperative atrial fibrillation in cardiac surgery.
AB  - OBJECTIVES: Postoperative new-onset atrial fibrillation (POAF) in cardiac surgery
      is associated with increased morbidity and mortality. Because n-3 polyunsaturated
      fatty acids (n-3 PUFA) have an antiarrhythmic effect, we hypothesized that a high
      content of marine n-3 PUFA in the atrial wall was associated with a reduced risk
      of POAF. DESIGN: Venous blood and tissue from the right atrial appendage were
      obtained from 50 patients undergoing elective cardiac surgery. We determined the
      content of marine n-3 PUFA in atrial tissue and in plasma phospholipids using gas
      chromatography. RESULTS: The mean age of the patients (results available from 49
      patients) was 66.0+/-10.4years, and 22, 14, 10 and 3 patients underwent coronary
      artery bypass surgery, valve, combined or other cardiac surgery, respectively.
      Eighteen patients (36.7%) developed POAF. Concentrations of n-3 PUFA in the
      atrial wall and in plasma phospholipids did not predict the development of POAF,
      but there were significant correlations between marine n-3 PUFA in atrial tissue
      and plasma. CONCLUSION: Levels of marine n-3 PUFA in the atrial wall was not
      associated with the risk of POAF following cardiac surgery, despite significant
      correlations of marine n-3 PUFA in the atrium and in plasma phospholipids.

PMID- 27867032
TI  - Neural correlates of temporal context retrieval for abstract scrambled phrases:
      Reducing narrative and familiarity-based strategies.
AB  - Temporal context, memory for the timing of events, can be assessed using non
      temporal strategies such as relative familiarity or inference from a semantic
      narrative. Neuroimaging studies, which have previously encouraged such
      strategies, find similar patterns of brain regions involved in both temporal and
      non-temporal context memory. The present study aims to investigate whether
      previous findings are driven by the use of non-temporal strategies or whether the
      same pattern of brain regions is identified when relative familiarity and
      semantic narrative strategies are discouraged. We used abstract phrases (e.g.
      alone me leave) created by scrambling familiar three-word phrases. The words in
      the phrases were less concrete than the object image stimuli used in previous
      studies of temporal context memory (Jenkins and Ranganath, 2010) and were
      presented quickly while participants read each word aloud. This differed from
      previous studies in which participants were encouraged to use narrative
      strategies during encoding (Tubridy and Davachi, 2011) and was designed to
      discourage use of narrative strategies. The relative familiarity of the words
      within each phrase was similar and likely not diagnostic of word order during
      encoding, in order to minimize the use of relative familiarity strategies.
      Neuroimaging results indicate that temporal context retrieval was associated with
      the hippocampus, parahippocampal cortex, ventromedial prefrontal cortex, and
      retrosplenial cortex, which are regions consistent with the retrieval of non
      temporal context in episodic memory, suggesting that previous findings were not
      driven entirely by non-temporal strategies but rather that temporal memory relies
      on similar brain regions to non-temporal memory.

PMID- 27867033
TI  - Differences in Abeta brain networks in Alzheimer's disease and healthy controls.
AB  - The prevailing beta-amyloid (Abeta)-cascade hypothesis is the most classical
      Alzheimer's disease (AD) pathogenesis. In this hypothesis, excessive Abeta plaque
      deposition in human brain is considered to be the cause of AD. Carbon 11-labeled
      Pittsburgh compound B Positron emission tomography (11C-PiB PET) is the latest
      technology to detect Abeta plaques in vivo. Thus, it is possible to investigate
      the difference of Abeta brain networks between AD patients and Health Controls
      (HC) by analyzing 11C-PiB PET images. In this study, a graph-theoretical method
      was employed to investigate the topological properties of Abeta networks in 18
      Chinese AD patients and 16 HC subjects from Huashan Hospital, Shanghai. The
      results showed that both groups demonstrated small-world property, and this
      property was more obvious in AD group. Additionally, the clustering coefficients
      and path lengths were significantly lower in AD group. The global efficiency was
      larger in AD than in HC. A direct comparison between with and without regression
      found that sex, age and weight had no significant effect on the Abeta network.
      Moreover, three altered regions in AD group were identified, including left
      cuneus (CUN.L), right caudate nucleus (CAU.R) and left superior frontal gyrus
      (SFGdor. L). A voxel-wise correlation analysis showed that in AD patients, the
      regions of strengthened connection with CUN.L were mainly located in frontal
      cortex and parietal cortex, the regions of strengthen connection with CAU.R were
      mainly located in temporal cortex. Finally, a machine learning based analysis
      demonstrated that the three regions could be better biomarkers than the whole
      brain for AD classification.

PMID- 27867034
TI  - The effects of NBM- lesion on synaptic plasticity in rats.
AB  - The nucleus basalis magnocellularis (NBM) is a major source of cholinergic
      projections to the neocortex that is vulnerable to degeneration in Alzheimer's
      disease. Despite numerous anatomical, pharmacological, behavioral, and
      physiological investigations of NBM, there is no in vivo study of its effects on
      short- or long-term synaptic plasticity. Hence, this study was devoted to the
      assessment of the effects of bilateral lesion of the NBM on synaptic plasticity
      in the dentate gyrus of the hippocampus using electrophysiological techniques.
      For this purpose, twenty-five male Wistar rats were randomly allocated into the
      three Control, Sham, and NBM-lesioned groups. Lesion was made via bilateral
      injections of 5ug/ul ibotenic acid. After twenty-one days, the input-output
      functions, paired-pulse facilitation/inhibition, and long-term potentiation (LTP)
      were evaluated in the dentate gyrus while the perforant pathway was stimulated.
      NBM lesion was found to attenuate the basal synaptic responsiveness, paired-pulse
      responses, and LTP in the rats' dentate gyrus, indicating that lesions of this
      cholinergic nucleus affects both short- and long-term neural plasticity in the
      dentate gyrus although NBM does not send direct cholinergic projections to the
      hippocampus.

PMID- 27867035
TI  - Two-Way Conversion between Lipogenic and Myogenic Fibroblastic Phenotypes Marks
      the Progression and Resolution of Lung Fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a form of progressive interstitial lung
      disease with unknown etiology. Due to a lack of effective treatment, IPF is
      associated with a high mortality rate. The hallmark feature of this disease is
      the accumulation of activated myofibroblasts that excessively deposit
      extracellular matrix proteins, thus compromising lung architecture and function
      and hindering gas exchange. Here we investigated the origin of activated
      myofibroblasts and the molecular mechanisms governing fibrosis formation and
      resolution. Genetic engineering in mice enables the time-controlled labeling and
      monitoring of lipogenic or myogenic populations of lung fibroblasts during
      fibrosis formation and resolution. Our data demonstrate a lipogenic-to-myogenic
      switch in fibroblastic phenotype during fibrosis formation. Conversely, we
      observed a myogenic-to-lipogenic switch during fibrosis resolution. Analysis of
      human lung tissues and primary human lung fibroblasts indicates that this fate
      switching is involved in IPF pathogenesis, opening potential therapeutic avenues
      to treat patients.

PMID- 27867038
TI  - Comparative mitogenomic analysis of three species of periwinkles: Littorina
      fabalis, L. obtusata and L. saxatilis.
AB  - The flat periwinkles, Littorina fabalis and L. obtusata, offer an interesting
      system for local adaptation and ecological speciation studies. In order to
      provide genomic resources for these species, we sequenced their mitogenomes
      together with that of the rough periwinkle L. saxatilis by means of next
      generation sequencing technologies. The three mitogenomes present the typical
      repertoire of 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA
      genes and a putative control region. Although the latter could not be fully
      recovered in flat periwinkles using short-reads due to a highly repetitive
      fragment, in L. saxatilis this problem was overcome with additional long-reads
      and we were able to assemble the complete mitogenome. Both gene order and
      nucleotide composition are similar between the three species as well as compared
      to other Littorinimorpha. A large variance in divergence was observed across
      mitochondrial regions, with six- to ten-fold difference between the highest and
      the lowest divergence rates. Based on nucleotide changes on the whole molecule
      and assuming a molecular clock, L. fabalis and L. obtusata started to diverge
      around 0.8 Mya (0.4-1.1 Mya). The evolution of the mitochondrial protein-coding
      genes in the three Littorina species appears mainly influenced by purifying
      selection as revealed by phylogenetic tests based on dN/dS ratios that did not
      detect any evidence for positive selection, although some caution is required
      given the limited power of the dataset and the implemented approaches.

PMID- 27867039
TI  - Peritoneal dialysis effluent miR-21 and miR-589 levels correlate with
      longitudinal change in peritoneal transport characteristics.
AB  - BACKGROUND: The role of microRNA (miRNA) in peritoneal fibrosis and longitudinal
      change in transport is uncertain. METHODS: We studied 80 new peritoneal dialysis
      (PD) patients. Peritoneal transport was determined by standard peritoneal
      equilibration test (PET) of creatinine at baseline. Based on published
      literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA
      quantification were repeated one year later in 46 patients. RESULTS: Baseline PD
      effluent levels of all targets tested had modest but significant correlation with
      peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated
      with dialysate-to-plasma creatinine concentration at 4h (D/P4) at baseline
      (r=0.377, p=0.001 and r=0.237, p=0.037, respectively) and after one year of PD
      (r=0.362, p=0.014 and r=0.402, p=0.007). The change in PD effluent -21 and miR
      589 levels over one year correlated with the corresponding change in D/P4
      (r=0.470, p=0.001 and r=0.479, p=0.002). The number of peritonitis episodes
      during follow up significantly correlated with the change in PD effluent miR-21
      (r=0.387, p=0.009) and miR-589 (r=0.336, p=0.027) levels. There was no
      significant correlation between PD effluent miRNA level and ultrafiltration
      volume. CONCLUSION: Amongst the 10 miRNA targets tested, miR-21 and miR-589
      showed consistently significant relation with peritoneal transport. Further
      studies are needed to delineate their mechanisms of regulating peritoneal
      transport.

PMID- 27867037
TI  - Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate
      Pathological Heart Calcification.
AB  - Mammalian tissues calcify with age and injury. Analogous to bone formation,
      osteogenic cells are thought to be recruited to the affected tissue and induce
      mineralization. In the heart, calcification of cardiac muscle leads to conduction
      system disturbances and is one of the most common pathologies underlying heart
      blocks. However the cell identity and mechanisms contributing to pathological
      heart muscle calcification remain unknown. Using lineage tracing, murine models
      of heart calcification and in vivo transplantation assays, we show that cardiac
      fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to
      heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is
      induced upon injury and regulates bone mineralization, significantly attenuated
      cardiac calcification. Inhibitors of bone mineralization completely prevented
      ectopic cardiac calcification and improved post injury heart function. Taken
      together, these findings highlight the plasticity of fibroblasts in contributing
      to ectopic calcification and identify pharmacological targets for therapeutic
      development.

PMID- 27867040
TI  - Epilepsy in MELAS.

PMID- 27867036
TI  - DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation.
AB  - Hematopoietic stem cells give rise to all blood cells in a differentiation
      process that involves widespread epigenome remodeling. Here we present genome
      wide reference maps of the associated DNA methylation dynamics. We used a meta
      epigenomic approach that combines DNA methylation profiles across many small
      pools of cells and performed single-cell methylome sequencing to assess cell-to
      cell heterogeneity. The resulting dataset identified characteristic differences
      between HSCs derived from fetal liver, cord blood, bone marrow, and peripheral
      blood. We also observed lineage-specific DNA methylation between myeloid and
      lymphoid progenitors, characterized immature multi-lymphoid progenitors, and
      detected progressive DNA methylation differences in maturing megakaryocytes. We
      linked these patterns to gene expression, histone modifications, and chromatin
      accessibility, and we used machine learning to derive a model of human
      hematopoietic differentiation directly from DNA methylation data. Our results
      contribute to a better understanding of human hematopoietic stem cell
      differentiation and provide a framework for studying blood-linked diseases.

PMID- 27867041
TI  - Infantile Epileptic Encephalopathy Associated With SCN2A Mutation Responsive to
      Oral Mexiletine.
AB  - BACKGROUND: Genetic alterations are significant causes of epilepsy syndromes;
      especially early-onset epileptic encephalopathies and voltage-gated sodium
      channelopathies are among the best described. Mutations in the SCN2A subunit of
      voltage-gated sodium channels have been associated with benign familial neonatal
      infantile seizures, generalized epilepsy febrile seizures plus, and an early
      onset infantile epileptic encephalopathy. METHOD: We describe two infants with
      medically refractory seizures due to a de novo SCN2A mutation. RESULTS: The first
      child responded to intravenous lidocaine with significant reduction in seizure
      frequency and was successfully transitioned to enteral mexiletine. Mexiletine was
      subsequently used in a second infant with reduction in seizure frequency.
      CONCLUSION: Class 1b antiarrhythmic agents, lidocaine and mexiletine, may be
      useful in infants with medically refractory early infantile epileptic
      encephalopathy secondary to mutations in SCN2A.

PMID- 27867042
TI  - Poly(ADP-ribose)polymerase-1 hyperactivation in neurodegenerative diseases: The
      death knell tolls for neurons.
AB  - Neurodegeneration is a salient feature of chronic refractory brain disorders like
      Alzheimer's, Parkinson's, Huntington's, amyotropic lateral sclerosis and acute
      conditions like cerebral ischemia/reperfusion etc. The pathological protein
      aggregates, mitochondrial mutations or ischemic insults typifying these disease
      conditions collude with and intensify existing oxidative stress and attendant
      mitochondrial dysfunction. Interlocking these mechanisms is poly(ADP-ribose)
      polymerase (PARP-1) hyperactivation that invokes a distinct form of neuronal cell
      death viz., 'parthanatos'. PARP-1, a typical 'moonlighting protein' by virtue of
      its ability to poly(ADP-ribosyl)ate a plethora of cellular proteins exerts
      diverse functions that impinge significantly on cellular processes. In addition,
      its interactions with various nuclear proteins like transcription factors and
      chromatin modifiers elicit varied transcriptional outcomes that wield
      pathological cellular responses. Further, emerging leitmotifs like mitochondrial
      and nucleolar PARPs and the novel aspects of gene expression regulation by PARP-1
      and poly(ADP-ribosyl)ation can provide a holistic view of PARP-1's influence on
      cell vitality. In this review, we discuss the pathological underpinnings of PARP
      1, with a special emphasis on mitochondrial dysfunction and cell death
      subroutines, in the realm of neurodegeneration. This would provide a deeper
      insight into the functions of PARP-1 in neurodegenerative conditions that would
      enable the development of more effective therapeutic strategies.

PMID- 27867043
TI  - Acute social stress-induced immunomodulation in pigs high and low responders to
      ACTH.
AB  - Pig husbandry is known as an intensive breeding system, piglets being submitted
      to multiple stressful events such as early weaning, successive mixing, crowding
      and shipping. These stressors are thought to impair immune defences and might
      contribute, at least partly, to the prophylactic use of antibiotics. Robustness
      was recently defined as the ability of an individual to express a high-production
      potential in a wide variety of environmental conditions. Increasing robustness
      thus appears as a valuable option to improve resilience to stressors and could be
      obtained by selecting piglets upon their adrenocortical activity. In this study,
      we aimed at depicting the consequences of an acute social stress on the immune
      capacity of piglets genetically selected upon divergent hypothalamic-pituitary
      adrenocortical (HPA) axis activity. For this purpose, we monitored neuroendocrine
      and immune parameters, in high- (HPAhi) and low- (HPAlo) responders to ACTH, just
      before and immediately after a one-hour mixing with unfamiliar conspecifics. As
      expected, stressed piglets displayed higher levels of circulating cortisol and
      norepinephrine. Blood cell count analysis combined to flow cytometry revealed a
      stress-induced leukocyte mobilization in the bloodstream with a specific
      recruitment of CD8alpha+ lymphocytes. Besides, one-hour mixing decreased LPS
      induced IL-8 and TNFalpha secretions in whole-blood assays (WBA) and reduced
      mononuclear cell phagocytosis. Altogether, our data demonstrate that acute social
      stress alters immune competence of piglets from both groups, and bring new
      insights in favour of good farming practices. While for most parameters high- and
      low-responders to ACTH behaved similarly, HPAhi piglets displayed higher number
      of CD4+ CD8alpha- T cells, as well as increased cytokine production in WBA (LPS
      induced TNFalpha and PIL-induced IL-8), which could confer them increased
      resistance to pathogens. Finally, a principal component analysis including all
      parameters highlighted that overall stress effects were less pronounced on
      piglets with a strong HPA axis. Thus, selection upon adrenocortical axis activity
      seems to reduce the magnitude of response to stress and appears as a good tool to
      increase piglet robustness.

PMID- 27867045
TI  - MinVar: A rapid and versatile tool for HIV-1 drug resistance genotyping by deep
      sequencing.
AB  - Genotypic monitoring of drug-resistance mutations (DRMs) in HIV-1 infected
      individuals is strongly recommended to guide selection of the initial
      antiretroviral therapy (ART) and changes of drug regimens. Traditionally,
      mutations conferring drug resistance are detected by population sequencing of the
      reverse transcribed viral RNA encoding the HIV-1 enzymes target by ART, followed
      by manual analysis and interpretation of Sanger sequencing traces. This process
      is labor intensive, relies on subjective interpretation from the operator, and
      offers limited sensitivity as only mutations above 20% frequency can be reliably
      detected. Here we present MinVar, a pipeline for the analysis of deep sequencing
      data, which allows reliable and automated detection of DRMs down to 5%. We
      evaluated MinVar with data from amplicon sequencing of defined mixtures of
      molecular virus clones with known DRM and plasma samples of viremic HIV-1
      infected individuals and we compared it to VirVarSeq, another virus variant
      detection tool exclusively working on Illumina deep sequencing data. MinVar was
      designed to be compatible with a diverse range of sequencing platforms and allows
      the detection of DRMs and insertions/deletions from deep sequencing data without
      the need to perform additional bioinformatics analysis, a prerequisite to a
      widespread implementation of HIV-1 genotyping using deep sequencing in routine
      diagnostic settings.

PMID- 27867044
TI  - Mitochondrial dysfunction in cancer chemoprevention by phytochemicals from
      dietary and medicinal plants.
AB  - Cancer chemoprevention, a scientific term coined by Dr. Sporn in the late
      seventies, implies use of natural or synthetic chemicals to block, delay or
      reverse carcinogenesis. Phytochemicals derived from edible and medicinal plants
      have been studied rather extensively for cancer chemoprevention using preclinical
      models in the past few decades. Nevertheless, some of these agents (e.g.,
      isothiocyanates from cruciferous vegetables like broccoli and watercress) have
      already entered into clinical investigations. Examples of widely studied and
      highly promising phytochemicals from edible and medicinal plants include
      cruciferous vegetable constituents (phenethyl isothiocyanate, benzyl
      isothiocyanate, and sulforaphane), withaferin A (WA) derived from a medicinal
      plant (Withania somnifera) used heavily in Asia, and an oriental medicine plant
      component honokiol (HNK). An interesting feature of these structurally-diverse
      phytochemicals is that they target mitochondria to provoke cancer cell-selective
      death program. Mechanisms underlying cell death induction by commonly studied
      phytochemicals have been discussed rather extensively and thus are not covered in
      this review article. Instead, the primary focus of this perspective is to discuss
      experimental evidence pointing to mitochondrial dysfunction in cancer
      chemoprevention by promising phytochemicals.

PMID- 27867046
TI  - Efficient production of an avian adeno-associated virus vector using insect
      cell/baculovirus expression system.
AB  - Recombinant avian adeno-associated virus (rAAAV) is a promising gene transfer
      vector for avian cells. Although rAAAV can be produced by co-transfection of
      HEK293 cells with three plasmids, both scalability and productivity of the
      transient transfection method can not meet the demand for large-scale in vivo
      experiments. In this study, a scalable rAAAV production method was established by
      using insect cell/baculovirus expression system. Three recombinant baculoviruses,
      namely BacARep, BacAVP and BacAGFP, were generated by transfection of Sf9 cells
      with the three plasmids expressing AAAV Rep genes, modified VP gene or the
      inverted terminal repeats-flanked green fluorescent protein (GFP) gene. After
      demonstration of the correct expression of AAAV genes, rAAAV-GFP was produced by
      triple infection of insect cells or triple transfection of HEK293 cells for
      comparison purpose. Electron microscopy revealed the formation of typical AAAV
      particles in the insect cells. Western blotting showed the correct assembly of
      rAAAV particles with a VP protein ratio similar to that of AAAV. Quantitative PCR
      showed that the insect cell-produced rAAAV yield was almost 25-fold higher than
      that produced by HEK293 cells. Fluorescent microscopy showed that the insect cell
      produced rAAAV could transfer GFP reporter gene into two avian cell types with
      similar transfer efficiency to that of HEK293 cell-produced rAAAV. These data
      suggest that insect cell/baculovirus expression system could be used for scalable
      production of rAAAV, and the viral vector produced could be used as the gene
      transfer vehicle for avian cells.

PMID- 27867047
TI  - Assessing the intra-species genetic variability in the clonal pathogen
      Campylobacter fetus: CRISPRs are highly polymorphic DNA markers.
AB  - Campylobacter fetus is a Gram-negative, microaerophilic bacterium that infects
      animals and humans. The subspecies Campylobacter fetus subsp. fetus (Cff) affects
      a broad range of vertebrate hosts and induces abortion in cows and sheep.
      Campylobacter fetus subsp. venerealis (Cfv) is restricted to cattle and causes
      the endemic disease bovine genital campylobacteriosis, which triggers
      reproductive problems and is responsible for major economic losses. Campylobacter
      fetus subsp. testudinum (Cft) has been isolated mostly from apparently healthy
      reptiles belonging to different species but also from ill snakes and humans.
      Genotypic differentiation of Cff and Cfv is difficult, and epidemiological
      information is scarce because there are few methods to study the genetic
      diversity of the strains. We analyze the efficacy of MLST, ribosomal sequences
      (23S gene and internal spacer region), and CRISPRs to assess the genetic
      variability of C. fetus in bovine and human isolates. Sequences retrieved from
      complete genomes were included in the analysis for comparative purposes. MLST and
      ribosomal sequences had scarce or null variability, while the CRISPR-cas system
      structure and the sequence of CRISPR1 locus showed remarkable diversity. None of
      the sequences here analyzed provided evidence of a genetic differentiation of Cff
      and Cfv in bovine isolates. Comparison of bovine and human isolates with Cft
      strains showed a striking divergence. Inter-host differences raise the
      possibility of determining the original host of human infections using CRISPR
      sequences. CRISPRs are the most variable sequences analyzed in C. fetus so far,
      and constitute excellent representatives of a dynamic fraction of the genome.
      CRISPR typing is a promising tool to characterize isolates and to track the
      source and transmission route of C. fetus infections.

PMID- 27867048
TI  - Feasibility and Learning Curve of Robotic Laparoendoscopic Single-Site Surgery in
      Gynecology.
AB  - Single-site laparoscopy has proven to be a desirable option for patients
      undergoing gynecologic surgery, with some studies indicating improved cosmesis
      and less perioperative pain compared with standard approaches. This study
      describes the safety and feasibility of a novel robotic laparoendoscopic single
      site surgery (R-LESS) platform as it is incorporated into a surgeon's practice
      with extensive multiport robotic surgical experience but limited LESS experience.
      We reviewed 83 women undergoing R-LESS by a single surgeon from September 2013
      through August 2015. Operative times (total operative time, console time, docking
      time) were collected prospectively for the first 53 cases, and total operative
      time was collected retrospectively for the next 30 cases. Clinical parameters,
      including age, estimated blood loss, body mass index (BMI), prior abdominal
      surgeries, conversion to laparotomy, procedure type, uterine weight, length of
      hospital stay, and complications, were retrospectively collected from medical
      charts. Eighty-two of 83 surgeries were completed successfully with a single
      incision. One surgery was converted to multiport robotics for para-aortic lymph
      node dissection. Twelve surgeries were performed for cancer (ovary 1, uterus 8,
      and cervix 3). Eight patients underwent pelvic lymph node biopsy. The median
      total operative time for hysterectomies was 128 minutes (range, 60-275). After
      the first 13 hysterectomies the total operative time and the console time
      decreased significantly from 165.3 to 131.1 minutes (p = .032) and from 84.9 to
      57.1 minutes (p = .028), respectively. Mean docking time halved from 7.8 minutes
      to 3.4 minutes comparing the first 10 cases to the last 10 cases. Surgical times
      were longer with larger BMIs, but the console time decreased with experience
      regardless of BMI. The mean uterine weight was 164 g (range, 30-460).
      Complications included 2 umbilical hernias (2.4%) and 1 conversion to multiport.
      In conclusion, R-LESS is a feasible and safe surgical platform for gynecologic
      procedures. A small number of cases are needed to significantly improve operative
      times when it is introduced on a surgeon's practice with limited experience in
      LESS but familiar with robotic surgery. Further study is needed to investigate
      the cost, benefits, and long-term outcomes of R-LESS.

PMID- 27867049
TI  - Improving Rates of Post-Essure Hysterosalpingography in an Urban Population Using
      Electronic Tracking Reminders.
AB  - STUDY OBJECTIVE: To demonstrate the efficacy of electronic reminders for follow
      up hysterosalpingography (HSG) after Essure hysteroscopic sterilization in an
      urban tertiary care hospital obstetrics and gynecology practice. DESIGN:
      Retrospective cohort study (Canadian Task Force classification II-3). SETTING:
      Obstetrics and gynecology practice at a university-affiliated urban tertiary care
      teaching hospital. PATIENTS: Two hundred and fifty patients who underwent Essure
      hysteroscopic sterilization between June 2011 and July 2014. INTERVENTION:
      Implementation of electronic reminders for the office staff. MEASUREMENTS AND
      MAIN RESULTS: Two hundred and fifty of 259 patients (96.5%) underwent Essure
      hysteroscopic sterilization and successful placement of coils into bilateral
      Fallopian tubes. Among these 250 patients, 135 (54%) returned for HSG at 3 months
      post-Essure as advised at the time of procedure. The use of electronic reminders
      prompted another 45 patients (18%) to return for HSG, improving the total post
      Essure follow-up rate to 72%. CONCLUSION: Electronic reminders for the office
      staff of an urban tertiary care hospital's obstetrics and gynecology practice is
      an effective method for improving the rate of post-Essure HSG.

PMID- 27867050
TI  - Laparoscopic Resection of Cesarean Scar Ectopic Pregnancy.
AB  - STUDY OBJECTIVE: To demonstrate a technique for the laparoscopic surgical
      management of cesarean section scar ectopic pregnancy. DESIGN: Step-by-step
      presentation of the procedure using video (Canadian Task Force classification
      III). SETTING: Cesarean section scar ectopic pregnancy is a rare form of ectopic
      pregnancy with an incidence ranging from 1:1800 to 1:2216. Over the last decade,
      the incidence seems to be on the rise with increasing rates of cesarean
      deliveries and early use of Doppler ultrasound. These pregnancies can lead to
      life-threatening hemorrhage, uterine rupture, and hysterectomy if not managed
      promptly. Local or systemic methotrexate therapy has been used successfully but
      can result in prolonged hospitalization, requires long-term follow-up, and in
      some cases treatment can fail. In the hands of a trained operator, laparoscopic
      resection can be performed to manage this type of pregnancy. PATIENT: Consent was
      obtained from the patient, and exemption was granted from the local Internal
      Review Board (The Womens' Hospital, Parkville). INTERVENTIONS, MEASUREMENTS AND
      MAIN RESULTS: In this video we describe our technique for laparoscopic management
      of a cesarean scar ectopic pregnancy. We present the case of a 34-year-old G4P2T1
      with the finding of a live 8-week pregnancy embedded in the cesarean section
      scar. The patient had undergone 2 previous uncomplicated cesarean sections at
      term. On presentation her beta-human chorionic gonadotropin (beta-hCG) level was
      52 405 IU/L. She was initially managed with an intragestational sac injection of
      potassium chloride and methotrexate, followed by 4 doses of intramuscular
      methotrexate. Despite these conservative measures, the level of beta-hCG did not
      adequately fall and an ultrasound showed a persistent 4-cm mass. A decision was
      made to proceed with surgical treatment in the form of a laparoscopic resection
      of the ectopic pregnancy. The surgery was uneventful, and the patient was
      discharged home within 24 hours of her procedure. Her serial beta-hCG levels were
      followed until complete resolution. CONCLUSION: Laparoscopic excision of cesarean
      section scar ectopic pregnancy is an effective procedure for the management of
      this increasingly more common condition. The use of vasopressin intraoperatively
      and laparoscopic suturing can prevent hemorrhage and allow for the safe removal
      of the ectopic pregnancy with multilayer repair of the uterine defect.

PMID- 27867051
TI  - Total Laparoscopic Hysterectomy Versus Vaginal Hysterectomy: A Systematic Review
      and Meta-Analysis.
AB  - Hysterectomies performed laparoscopically have greatly increased within the last
      few decades and even exceed the number of vaginal hysterectomies (VHs). This
      systematic review, conducted according to the Meta-analysis of Observational
      Studies in Epidemiology guidelines, compares surgical outcomes of total
      laparoscopic hysterectomy (TLH) and VH to evaluate which approach offers the most
      benefits. A literature search was performed in PubMed, Embase, and Web of Science
      for all relevant publications from January 2000 to February 2016. All randomized
      controlled trials and cohort studies for benign indication or low-grade
      malignancy comparing TLH with VH were considered for inclusion. From the
      literature search, 24 articles were found to be relevant and included in this
      review. The results of our meta-analysis showed no difference between the 2
      groups for overall complications (OR 1.24 [.68, 2.28] for major complications; OR
      .83 [.53, 1.28] for minor complications), risk of ureter and bladder injuries (OR
      .81 [.34, 1.92]), intraoperative blood loss (mean difference [MD] -30 mL [-67.34,
      7.60]), and length of hospital stay (-.61 days [-1.23, -.01]). VH was associated
      with a shorter operative time (MD 42 minute [29.34, 55.91]) and a lower rate of
      vaginal cuff dehiscence (OR 6.28 [2.38, 16.57]) and conversion to laparotomy (OR
      3.89 [2.18, 6.95]). Although not significant, the costs of procedure were lower
      for VH (MD 3889.9 dollars [2120.3, 89 000]). Patients in the TLH group had lower
      postoperative visual analog scale scores (MD -1.08, [-1.74, -.42]) and required
      less analgesia during a shorter period of time (MD -.64 days, [-1.06, -.22]).
      Defining the best surgical approach is a dynamic process that requires frequent
      re-evaluation as techniques improve. Although TLH and VH result in similar
      outcomes, our meta-analysis showed that when both procedures are feasible, VH is
      currently still associated with greater benefits, such as shorter operative time,
      lower rate of vaginal dehiscence and conversion to laparotomy, and lower costs.
      Many factors influence the choice for surgical approach to hysterectomy, and
      shared decision-making is recommended.

PMID- 27867052
TI  - Accelerating MRI fat quantification using a signal model-based dictionary to
      assess gastric fat volume and distribution of fat fraction.
AB  - To quantify intragastric fat volume and distribution with accelerated magnetic
      resonance (MR) imaging using signal model-based dictionaries (DICT) in comparison
      to conventional parallel imaging (CG-SENSE). This study was approved by the local
      ethics committee and written informed consent was obtained. Seven healthy
      subjects were imaged after intake of a lipid emulsion and data at three different
      time points during the gastric emptying process was acquired in order to cover a
      range of fat fractions. Fully sampled and prospectively undersampled image data
      at a reduction factor of 4 were acquired using a multi gradient echo sequence at
      1.5T. Retrospectively and prospectively undersampled data were reconstructed with
      DICT and CG-SENSE. Image quality of the retrospectively undersampled data was
      assessed relative to the fully sampled reference using the root mean square error
      (RMSE). In order to assess the agreement of fat volumes and intragastric fat
      distribution, Bland-Altman analysis and linear regression were performed on the
      data. The RMSE in intragastric content (DeltaRMSE=0.10+/-0.01, P<0.001) decreased
      significantly with DICT relative to CG-SENSE. CG-SENSE overestimated fat volumes
      (bias 2.1+/-1.3mL; confidence limits 5.4 and -1.1mL) in comparison to the
      prospective DICT reconstruction (bias -0.1+/-0.7mL; confidence limits 1.8 and 
      2.0mL). There was a good agreement in fat distribution between the images
      reconstructed by retrospective DICT and the reference images (regression slope:
      1.01, R2=0.961). Accelerating gastric MRI by integrating a dictionary-based
      signal model allows for improved image quality and increases accuracy of fat
      quantification during breathholds.

PMID- 27867053
TI  - Intra voxel analysis in magnetic resonance imaging.
AB  - A technique for analyzing the composition of each voxel, in the magnetic
      resonance imaging (MRI) framework, is presented. By combining different
      acquisitions, a novel methodology, called intra voxel analysis (IVA), for the
      detection of multiple tissues and the estimation of their spin-spin relaxation
      times is proposed. The methodology exploits the sparse Bayesian learning (SBL)
      approach in order to solve a highly underdetermined problem imposing the solution
      sparsity. IVA, developed for spin echo imaging sequence, can be easily extended
      to any acquisition scheme. For validating the approach, simulated and real data
      sets are considered. Monte Carlo simulations have been implemented for evaluating
      the performances of IVA compared to methods existing in literature. Two clinical
      datasets acquired with a 3T scanner have been considered for validating the
      approach. With respect to other approaches presented in literature, IVA has
      proved to be more effective in the voxel composition analysis, in particular in
      the case of few acquired images. Results are interesting and very promising: IVA
      is expected to have a remarkable impact on the research community and on the
      diagnostic field.

PMID- 27867054
TI  - Thiolated methylated dimethylaminobenzyl chitosan: A novel chitosan derivative as
      a potential delivery vehicle.
AB  - Chitosan is a natural mucoadhesive, biodegradable, biocompatible and nontoxic
      polymer which has been used in pharmaceutical industry for a lot of purposes such
      as dissolution enhancing, absorption enhancing, sustained releasing and protein,
      gene or drug delivery. Two major disadvantages of chitosan are poor solubility in
      physiological pH and low efficiency for protein and gene delivery. In this study
      thiolated methylated N-(4-N,N-dimethylaminobenzyl) chitosan was prepared for the
      first time in order to improve the solubility and delivery properties of
      chitosan. This novel chitosan derivative was characterized using 1H NMR, Ellman
      test, TGA and Zetasizer. Cell toxicity studies were performed on Human Embryonic
      Kidney 293 (Hek293) cell line using XTT method, to investigate the potential
      effect of this new derivative on cell viability. 1H NMR results showed that all
      substitution reactions were successfully carried out. Zeta potential of new
      derivative at acidic and physiological pHs was greater than chitosan and it
      revealed an increase in solubility of the derivative. Furthermore, it had no
      significant cytotoxicity against Hek293 cell line in comparison to chitosan.
      These findings confirm that this new derivative can be introduced as a suitable
      compound for biomedical purposes.

PMID- 27867055
TI  - Heterologous expression and functional characterization of phytaspase, a caspase
      like plant protease.
AB  - Following the cloning and expression of tobacco (Nicotiana tabacum) phytaspase
      gene in Escherichia coli BL21, the recombinant protease was purified by affinity
      chromatography for further characterization. Circular dichroism (CD) spectroscopy
      and in silico analysis revealed structural similarities of recombinant phytaspase
      with other plant serine-proteases. Molecular docking studies showed favourable
      binding of synthetic peptide substrate for caspase 8 (Ac-VETD-AMC) to the
      reactive pocket of recombinant phytaspase indicating its potential in assessing
      functional activity of recombinant phytaspase. In silico findings were supported
      by caspase 8-like activity of purified phytaspase demonstrated in vitro. The
      Michaelis constant (KM) and specificity constant (kcat/KM) of phytaspase for
      hydrolyzing Ac-VETD-AMC were found to be 1.587MUM and 4.67*103M-1min-1,
      respectively. Transient expression of phytaspase in lung epithelial
      adenocarcinoma cells (A549) resulted in reduced IC50 value of doxorubicin. This
      is the first report of functional expression of mature phytaspase in bacterial
      system as well as its transfection to sensitize A549 cells at lower doxorubicin
      concentration.

PMID- 27867056
TI  - Manipulation of pH-Sensitive interactions between podophyllotoxin-chitosan for
      enhanced controlled drug release.
AB  - Podophyllotoxin (PPT) offers a broad-spectrum of anticancer activities, but
      little has been reported for its controlled release. This work shows that by
      manipulating molecular interactions between PPT and Chitosan, efficient nanoscale
      capsulation of PPT can be realized. The drug encapsulation efficiency is as high
      as 52%, with a final particle drug loading in the order of 10% (wt/wt). It
      further demonstrates that changes in pH can also significantly affect the rate of
      drug release from the Chitosan nanoparticles. Upon contact with cancer cells,
      chitosan nanoparticles enable efficient internalization and drug release. In
      vitro evaluations with HepG-2 and MCF-7 cells indicate that the chitosan
      nanoparticle carriers can improve drug efficacy in comparison to free PPT, most
      likely by regulating the intrinsic apoptotic signaling pathway to induce
      apoptosis. Overall, PPT chitosan nanoparticles promise a safe and efficient drug
      delivery system for PPT.

PMID- 27867057
TI  - Understanding protein domain-swapping using structure-based models of protein
      folding.
AB  - In domain-swapping, two or more identical protein monomers exchange structural
      elements and fold into dimers or multimers whose units are structurally similar
      to the original monomer. Domain-swapping is of biotechnological interest because
      inhibiting domain-swapping can reduce disease-causing fibrillar protein
      aggregation. To achieve such inhibition, it is important to understand both the
      energetics that stabilize the domain-swapped structure and the protein dynamics
      that enable the swapping. Structure-based models (SBMs) encode the folded
      structure of the protein in their potential energy functions. SBMs have been
      successfully used to understand diverse aspects of monomer folding. Symmetrized
      SBMs model interactions between two identical protein chains using only intra
      monomer interactions. Molecular dynamics simulations of such symmetrized SBMs
      have been used to correctly predict the domain-swapped structure and to
      understand the mechanism of domain-swapping. Here, we review such models and
      illustrate that monomer topology determines key aspects of domain-swapping.
      However, in some proteins, specifics of local energetic interactions modulate
      domain-swapping and these need to be added to the symmetrized SBMs. We then
      summarize some general principles of the mechanism of domain-swapping that emerge
      from the symmetrized SBM simulations. Finally, using our own results, we explore
      how symmetrized SBMs could be used to design domain-swapping in proteins.

PMID- 27867058
TI  - Application of Strep-Tactin XT for affinity purification of Twin-Strep-tagged
      CB2, a G protein-coupled cannabinoid receptor.
AB  - Human cannabinoid receptor CB2 belongs to the class A of G protein-coupled
      receptor (GPCR). CB2 is predominantly expressed in membranes of cells of immune
      origin and is implicated in regulation of metabolic pathways of inflammation,
      neurodegenerative disorders and pain sensing. High resolution structural studies
      of CB2 require milligram quantities of purified, structurally intact protein.
      While we previously reported on the methodology for expression of the recombinant
      CB2 and its stabilization in a functional state, here we describe an efficient
      protocol for purification of this protein using the Twin-Strep-tag/Strep-Tactin
      XT system. To improve the affinity of interaction of the recombinant CB2 with the
      resin, the double repeat of the Strep-tag (a sequence of eight amino acids
      WSHPQFEK), named the Twin-Strep-tag was attached either to the N- or C-terminus
      of CB2 via a short linker, and the recombinant protein was expressed in
      cytoplasmic membranes of E. coli as a fusion with the N-terminal maltose binding
      protein (MBP). The CB2 was isolated at high purity from dilute solutions
      containing high concentrations of detergents, glycerol and salts, by capturing
      onto the Strep-Tactin XT resin, and was eluted from the resin under mild
      conditions upon addition of biotin. Surface plasmon resonance studies performed
      on the purified protein demonstrate the high affinity of interaction between the
      Twin-Strep-tag fused to the CB2 and Strep-Tactin XT with an estimated Kd in the
      low nanomolar range. The affinity of binding did not vary significantly in
      response to the position of the tag at either N- or C-termini of the fusion. The
      binding capacity of the resin was several-fold higher for the tag located at the
      N-terminus of the protein as opposed to the C-terminus- or middle of the fusion.
      The variation in the length of the linker between the double repeats of the Strep
      tag from 6 to 12 amino acid residues did not significantly affect the binding.
      The novel purification protocol reported here enables efficient isolation of a
      recombinant GPCR expressed at low titers in host cells. This procedure is
      suitable for preparation of milligram quantities of stable isotope-labelled
      receptor for high-resolution NMR studies.

PMID- 27867059
TI  - Pre- and unplanned walking turns in Parkinson's disease - Effects of dopaminergic
      medication.
AB  - Although dopaminergic medication improves functional mobility in individuals with
      Parkinson's disease (PD), its effects on walking turns are uncertain. Our goals
      was to determine whether dopaminergic medication improves preplanned and
      unplanned walking turns in individuals with PD, compared to healthy controls.
      Nineteen older adults with mild-to-moderate PD and 17 healthy controls performed
      one of the following three tasks, presented randomly: walking straight, or
      walking and turning 180 degrees  to the right or left. The walking direction was
      visually cued before starting to walk (preplanned) or after (unplanned, i.e.,
      0.6m before reaching the turning point). Subjects with PD were assessed off
      dopaminergic medication (OFF) and on dopaminergic medication (ON) medication.
      Turning strategy (step and spin turns), turning performance (turning distance and
      body rotation) and walking pattern were analyzed for three turning steps.
      Irrespective of medication state and turning condition, step and spin turns
      followed a nearly 50:50 distribution. After intake of dopaminergic medication,
      subjects with PD increased their turning distance but not the amount of body
      rotation or their walking pattern. Compared to controls, turning impairments in
      subjects with PD remained while ON medication and problems regulating step width
      were the most prominent features of their walking pattern. Specifically, subjects
      with PD turned with narrower cross-over steps, i.e. when the external foot
      crossed over the line of progression of the internal leg. We conclude that
      turning impairments remained even after dopaminergic medication and problems
      modulating step width appears to be a critical feature for turning in PD.

PMID- 27867061
TI  - Interaction between DRD2 variation and sound environment on mood and emotion
      related brain activity.
AB  - Sounds, like music and noise, are capable of reliably affecting individuals' mood
      and emotions. However, these effects are highly variable across individuals. A
      putative source of variability is genetic background. Here we explored the
      interaction between a functional polymorphism of the dopamine D2 receptor gene
      (DRD2 rs1076560, G>T, previously associated with the relative expression of D2S/L
      isoforms) and sound environment on mood and emotion-related brain activity.
      Thirty-eight healthy subjects were genotyped for DRD2 rs1076560 (G/G=26; G/T=12)
      and underwent functional magnetic resonance imaging (fMRI) during performance of
      an implicit emotion-processing task while listening to music or noise. Individual
      variation in mood induction was assessed before and after the task. Results
      showed mood improvement after music exposure in DRD2GG subjects and mood
      deterioration after noise exposure in GT subjects. Moreover, the music, as
      opposed to noise environment, decreased the striatal activity of GT subjects as
      well as the prefrontal activity of GG subjects while processing emotional faces.
      These findings suggest that genetic variability of dopamine receptors affects
      sound environment modulations of mood and emotion processing.

PMID- 27867060
TI  - The role of Efr3a in age-related hearing loss.
AB  - Efr3a has been found to be involved in the functional maintenance and structural
      degeneration of sensory and motor nervous tissues. Our previous data have
      suggested that Efr3a may be associated with the initiation of the degeneration of
      spiral ganglion neurons (SGNs). In this study, we used Efr3a knockdown (Efr3a KD)
      and Efr3a overexpression (Efr3a OE) mice to determine the role of Efr3a in age
      related hearing loss. Measurements of hearing thresholds showed that Efr3a had
      little or no influence on the hearing threshold at all frequencies in adult mice,
      whereas in an early stage of senescence, Efr3a reduction resulted in better
      hearing function, especially at 10 and 12months of age. No significant
      differences were observed in hair cell loss among the three groups until
      14months. The number of surviving hair cells in the OE mice was lower than that
      in the KD mice. As indicated by the density of SGNs in the upper basal turn, the
      Efr3a OE mice displayed earlier and more severe degeneration than the KD mice. In
      addition, the p-Akt levels in the cochlear spiral ganglions were higher in adult
      Efr3a KD mice than in WT and OE mice, although there was no difference in Akt
      expression among the three groups. Our study suggests that down-regulation of
      Efr3a might improve hearing function and alleviate the degeneration of SGNs in an
      early stage of senescence, probably via enhancing the basal expression of
      activated Akt.

PMID- 27867062
TI  - Evaluation of convalescent whole blood for treating Ebola Virus Disease in
      Freetown, Sierra Leone.
AB  - BACKGROUND: Convalescent blood therapy has been a promising form of treatment for
      Ebola Virus Disease (EVD), but less attention has been focused on it for
      treatment. METHOD: We assessed the effectiveness of convalescent whole blood
      (CWB) in the treatment of consented EVD patients. We recruited 69 subjects in
      December 2014 up to April 2015, at the 34 Military Hospital in Wilberforce and
      the PTS 1 Ebola Treatment Unit in Hastings, Freetown. Forty-four were given CWB,
      and 25 who consented but preferred to be exempted from the CWB treatment were
      used to compare clinical outcomes. All were given routine treatment used at the
      Ebola Treatment Unit. RESULTS: One of 44 subjects treated with CWB dropped out of
      the study and 31 recovered while 12 succumbed to the disease with a case fatality
      rate of 27.9%. For the group that was given routine treatment without CWB, 11
      died with a case fatality rate of 44%. There was a significant difference between
      admission viral load and viral load after the first 24 h of treatment with
      convalescent whole blood (P < 0.01). The odds ratio for survival with CWB was 2.3
      (95% CI, 0.8-6.5). CONCLUSION: CWB is promising for treating EVD in resource-poor
      settings, especially in the early phases of outbreaks when resource-mobilization
      is done. Even though our sample size was small and the evaluation was not
      randomised, our results contribute to existing evidence that convalescent whole
      blood could be considered as a useful candidate for treating EVD. Further studies
      that are randomised will be required to further assess the efficacy of CWB as
      treatment option during any EVD outbreak.

PMID- 27867064
TI  - ?

PMID- 27867065
TI  - Condylar resorptions and orthodontic-surgical treatment: State of the art.
AB  - Resorption of the mandibular condyle [RMC] is a disease of the temporomandibular
      joints, with multifactorial origins. The clinical manifestations take the form
      essentially of joint pain and occlusal disorders, depending on the rate at which
      the condyle is affected. X-ray imaging shows that the condyle is reduced in
      volume, flattened and displaced backwards, with loss of cortical substance in
      advanced forms. The aim of this article is to recall some pathophysiological
      features and then to review all the diagnostic and etiological factors and
      discuss possible modes of management.

PMID- 27867066
TI  - ?

PMID- 27867067
TI  - ?

PMID- 27867063
TI  - Neonatal listeriosis in the UK 2004-2014.
AB  - OBJECTIVE: To define the clinical features and outcomes of neonatal listeriosis,
      and identify the maternal risk factors to seek scope for improvement. METHODS:
      Neonatal listeriosis was identified prospectively from a United Kingdom neonatal
      infection surveillance network (neonIN) between 2004 and 2014. The participating
      neonatal units completed a study-specific proforma. RESULTS: The incidence of
      neonatal listeriosis was 3.4 per 100,000 live births. Of the 21 cases identified,
      19 were confirmed with a median gestational age of 33 weeks and a median birth
      weight of 1960 g. The majority had clinical features (95%, 18/19), presented
      within the first 24 h (95%, 18/19), and received penicillin empirically (94%,
      18/19). The neonatal case-fatality rate was 21% (24% if probable cases were
      included). A proportion of mothers were investigated (60%, 12/18) and diagnosed
      with listeriosis (58%, 7/12); 32% (6/19) were treated with antibiotics but only
      33% (6/12) included penicillin. DISCUSSION: Despite its rarity and the prompt and
      appropriate use of antibiotics neonatal listeriosis has a high case-fatality
      rate. There is room for improvement in the adherence to the empiric antibiotic
      choice for puerperal sepsis, according to the national guidelines as this, would
      target listeriosis. Strategies should be in place to prevent pregnancy-associated
      listeriosis in higher risk population.

PMID- 27867068
TI  - Evaluation of arch forms depending on the angle classification.
AB  - : It is generally accepted that each individual has his or her own dental arch
      form. However, during orthodontic treatment, industrially preshaped archwires are
      widely used. The resulting use of the same arch form for all malocclusions may
      compromise occlusal stability after orthodontic treatment. AIM: To determine the
      average dental arch form of a non-consulting Moroccan population depending on the
      Angle classification, after digitization of plaster models of the dental arches.
      MATERIAL AND METHODS: A sample of 50 dental students aged between 21 and 27 was
      selected. After digitization of the plaster models to produce a cloud of points,
      the barycentric method was applied to this representation, enabling all the arch
      shapes of each series to be superimposed with Photoshop CS 5 software (layer
      mode) and the average curves for each Angle class to be thereby determined.
      RESULTS: The average maxillary and mandibular arch forms were defined for each
      class: Class I: a normal maxillary form and an ovoid mandibular form; Class II: a
      tapered maxillary form and a narrow tapered mandibular form; Class III: narrow
      tapered forms for both upper and lower arches. Globally speaking, in this sample
      an ovoid mandibular arch form and a normal maxillary arch form are the dominant
      shapes. DISCUSSION AND CONCLUSION: The studied population exhibited specific arch
      form features. This study could serve as the basis for the choice and use of
      preformed archwires better-adapted to the needs of our patients.

PMID- 27867069
TI  - Statistical study on bracket debonding rate with the win lingual technique.
AB  - The aim of this study is to present the results of a statistical inquiry
      measuring the bracket debonding rate using the WIN lingual technique. This
      inquiry was performed in the Odontology Unit at the Rothschild Hospital in the
      framework of the Lingual Orthodontics University Diploma at Paris VII university.
      Results were gathered by 8 orthodontic practitioners during two years of training
      from all their patients treated with the WIN lingual technique. The sample study
      comprised 33 patients treated exclusively with the WIN lingual technique. The 8
      practitioners filled in a questionnaire relating to bracket bond failure in their
      patients in the course of treatment. In all, sixty-two questionnaires were
      analyzed. The data were then computed using the statistical tool of R software
      version 3.1.3. The results of this analysis demonstrate the reliability of the
      WIN system evidenced by an average of 2.1 bracket bond failures over the two-year
      treatment period, i.e. approximately 1 bracket per patient per year. Given the
      right conditions, (precise prescription, compliance with bonding protocols), the
      bond failure rate can be lower still, even compared with the buccal technique or
      relative to other lingual techniques. The benefits of lingual appliances,
      particularly in the WIN system, are essential to clinicians in their daily
      practice in order to optimize the quality and duration of their treatments with a
      view to ensuring patient satisfaction.

PMID- 27867071
TI  - Evaluation of a novel high-resolution mapping system for catheter ablation of
      ventricular arrhythmias.
AB  - BACKGROUND: The mapping of ventricular arrhythmias in humans using a minibasket
      64-electrode catheter paired with a novel automatic mapping system (Rhythmia) has
      not been evaluated. OBJECTIVE: The purpose of this study was to evaluate the
      safety and efficacy of mapping ventricular arrhythmias and clinical outcomes
      after ablation using this system. METHODS: Electroanatomic maps for ventricular
      arrhythmias were obtained during 20 consecutive procedures in 19 patients (12
      with ventricular tachycardia [VT] and 2 with ventricular ectopy [VE]). High
      density maps were acquired using automatic beat acceptance and automatic system
      annotation of electrograms. RESULTS: Forty-seven electroanatomic maps (including
      3 right ventricular and 9 epicardial maps) were obtained. Left ventricular
      endocardial mapping by transseptal (n = 13) and/or transaortic (n = 11) access
      was safe with no complications related to the minibasket catheter. VT substrate
      maps (n = 14; median 10,184 points) consistently demonstrated late potentials
      with high resolution. VT activation maps (n = 25; median 6401 points) obtained by
      automatic annotation included 7 complete maps (covering >=90% of the tachycardia
      cycle length) in 5 patients in whom the entire VT circuit was accurately
      visualized. VE timing maps (n = 8) successfully localized the origin of VEs in
      all, with all accepted beats consistent with clinical VEs. Over a median follow
      up of 10 months, no arrhythmia recurrence was noted in 75% after VT ablation and
      86% after VE ablation. CONCLUSION: In this first human experience for ventricular
      arrhythmias using this system, ultra-high-density maps were created rapidly and
      safely, with a reliable automatic annotation of VT and consistent recording of
      abnormal electrograms. Medium-term outcomes after ablation were encouraging.
      Further larger studies are needed to validate these findings.

PMID- 27867070
TI  - The Shh Topological Domain Facilitates the Action of Remote Enhancers by Reducing
      the Effects of Genomic Distances.
AB  - Gene expression often requires interaction between promoters and distant
      enhancers, which occur within the context of highly organized topologically
      associating domains (TADs). Using a series of engineered chromosomal
      rearrangements at the Shh locus, we carried out an extensive fine-scale
      characterization of the factors that govern the long-range regulatory
      interactions controlling Shh expression. We show that Shh enhancers act
      pervasively, yet not uniformly, throughout the TAD. Importantly, changing intra
      TAD distances had no impact on Shh expression. In contrast, inversions disrupting
      the TAD altered global folding of the region and prevented regulatory contacts in
      a distance-dependent manner. Our data indicate that the Shh TAD promotes distance
      independent contacts between distant regions that would otherwise interact only
      sporadically, enabling functional communication between them. In large genomes
      where genomic distances per se can limit regulatory interactions, this function
      of TADs could be as essential for gene expression as the formation of insulated
      neighborhoods.

PMID- 27867073
TI  - Immune status assessment in adult lung transplant candidates.
AB  - BACKGROUND: Lung transplant recipients have an increased susceptibility to a
      variety of infections due to immunosuppressive therapy. Current guidelines
      recommend pneumococcal and other vaccinations, prior to lung transplantation to
      protect against post-transplant infections, but measurement of the antibody
      response to vaccination is not advised. Immune status investigation in lung
      transplant candidates, including the response to pneumococcal polysaccharide
      vaccination, has not been described. METHODS: Immune status investigation,
      including measurement of immunoglobulins, complement and the response to 23
      valent pneumococcal polysaccharide vaccination (23vPPV) was performed in 81 adult
      lung transplant candidates. RESULTS: Eighteen patients had low IgG levels and 32
      patients had low IgG1 and/or IgG2 levels. After vaccination with 23vPPV the
      median antibody concentration of all serotypes increased significantly. Fifty-two
      patients had protective IgG-post-vaccination antibody levels to at least 10
      serotypes. Twenty-nine patients had an impaired response to 23vPPV. CONCLUSIONS:
      In conclusion, a significant proportion of our cohort of lung transplant
      candidates had one or more abnormalities in the immune status. It is likely that
      these patients have an increased risk for infections after transplantation.
      Revaccination, including measurement of antibody response, and possibly antibody
      replacement therapy should be considered to minimize infection risk.

PMID- 27867072
TI  - Changes in electrical dyssynchrony by body surface mapping predict left
      ventricular remodeling in patients with cardiac resynchronization therapy.
AB  - BACKGROUND: Electrical activation is important in cardiac resynchronization
      therapy (CRT) response. Standard electrocardiographic analysis may not accurately
      reflect the heterogeneity of electrical activation. OBJECTIVE: We compared
      changes in left ventricular size and function after CRT to native electrical
      dyssynchrony and its change during pacing. METHODS: Body surface isochronal maps
      using 53 anterior and posterior electrodes as well as 12-lead electrocardiograms
      were acquired after CRT in 66 consecutive patients. Electrical dyssynchrony was
      quantified using standard deviation of activation times (SDAT). Ejection fraction
      (EF) and left ventricular end-systolic volume (LVESV) were measured before CRT
      and at 6 months. Multiple regression evaluated predictors of response. RESULTS:
      ?LVESV correlated with ?SDAT (P = .007), but not with ?QRS duration (P = .092).
      Patients with SDAT >=35 ms had greater increase in EF (13 +/- 8 units vs 4 +/- 9
      units; P < .001) and LVESV (-34% +/- 28% vs -13% +/- 29%; P = .005). Patients
      with >=10% improvement in SDAT had greater ?EF (11 +/- 9 units vs 4 +/- 9 units;
      P = .010) and ?LVESV (-33% +/- 26% vs -6% +/- 34%; P = .001). SDAT >=35 ms
      predicted ?EF, while ?SDAT, sex, and left bundle branch block predicted ?LVESV.
      In 34 patients without class I indication for CRT, SDAT >=35 ms (P = .015) and
      ?SDAT >=10% (P = .032) were the only predictors of ?EF. CONCLUSION: Body surface
      mapping of SDAT and its changes predicted CRT response better than did QRS
      duration. Body surface mapping may potentially improve selection or optimization
      of CRT patients.

PMID- 27867074
TI  - Toxicity of Cry1A toxins from Bacillus thuringiensis to CF1 cells does not
      involve activation of adenylate cyclase/PKA signaling pathway.
AB  - Bacillus thuringiensis (Bt) bacteria produce Cry toxins that are able to kill
      insect pests. Different models explaining the mode of action of these toxins have
      been proposed. The pore formation model proposes that the toxin creates pores in
      the membrane of the larval midgut cells after interaction with different
      receptors such as cadherin, aminopeptidase N and alkaline phosphatase and that
      this pore formation activity is responsible for the toxicity of these proteins.
      The alternative model proposes that interaction with cadherin receptor triggers
      an intracellular cascade response involving protein G, adenylate cyclase (AC) and
      protein kinase A (PKA). In addition, it was shown that Cry toxins induce a
      defense response in the larvae involving the activation of mitogen-activated
      kinases such as MAPK p38 in different insect orders. Here we analyzed the
      mechanism of action of Cry1Ab and Cry1Ac toxins and a collection of mutants from
      these toxins in the insect cell line CF1 from Choristoneura fumiferana, that is
      naturally sensitive to these toxins. Our results show that both toxins induced
      permeability of K+ ions into the cells. The initial response after intoxication
      with Cry1Ab and Cry1Ac toxins involves the activation of a defense response that
      involves the phosphorylation of MAPK p38. Analysis of activation of PKA and AC
      activities indicated that the signal transduction involving PKA, AC and cAMP was
      not activated during Cry1Ab or Cry1Ac intoxication. In contrast we show that
      Cry1Ab and Cry1Ac activate apoptosis. These data indicate that Cry toxins can
      induce an apoptotic death response not related with AC/PKA activation. Since
      Cry1Ab and Cry1Ac toxins affected K+ ion permeability into the cells, and that
      mutant toxins affected in pore formation are not toxic to CF1, we propose that
      pore formation activity of the toxins is responsible of triggering cell death
      response in CF1cells.

PMID- 27867075
TI  - Sexually dimorphic traits in the silkworm, Bombyx mori, are regulated by
      doublesex.
AB  - The DM domain genes, doublesex (dsx) in insects, or their structural homologs,
      male abnormal 3 (mab-3) in nematodes and Dmrt1 (doublesex and mab-3-related
      transcription factor 1) in mammals, are downstream regulators of the sex
      determination pathway that control sexually dimorphic development. Despite the
      functional importance of dsx and its potential applications in sterile insect
      technologies (SITs), the mechanisms by which it controls sexually dimorphic
      traits and the subsequent developmental gene networks in insects are poorly
      understood. Phylogenetic analyses indicate that insect dsx genes have sex
      specific alternative splicing isoforms, whereas other taxa do not. We exploited
      genome editing and transgenesis technologies to induce mutations in either the
      male-specific isoform (dsxM) or common region (dsxC) of dsx in the somatic
      tissues of the lepidopteran model insect Bombyx mori. Disruptions of gene
      function produced either male-specific sexually-dimorphic defects or intersexual
      phenotypes; these results differ from those observed in other insects, including
      Drosophila melanogaster. Our data provide insights into the divergence of the
      insect sex determination pathways related to the most conserved downstream
      component dsx.

PMID- 27867076
TI  - The DNA chaperone HMGB1 potentiates the transcriptional activity of Rel1A in the
      mosquito Aedes aegypti.
AB  - High Mobility Group protein 1 (HMGB1) is a non-histone, chromatin-associated
      nuclear protein that functions in regulating eukaryotic gene expression. We
      investigated the influence and mechanism of action of Aedes aegypti HMGB1
      (AaHMGB1) on mosquito Rel1A-mediated transcription from target gene promoters.
      The DNA-binding domain (RHD) of AaRel1A was bacterially expressed and purified,
      and AaHMGB1 dramatically enhanced RHD binding to consensus NF-kB/Rel DNA response
      elements. Luciferase reporter analyses using a cecropin gene promoter showed that
      AaHMGB1 potentiates the transcriptional activity of AaRel1A in Aag-2 cells.
      Moreover, overexpression of AaHMGB1 in Aag-2 cells led to an increase in mRNA
      levels of antimicrobial peptide genes. In vitro GST pull-down assays revealed
      that the presence of DNA is a pre-requisite for assembly of a possible ternary
      complex containing DNA, AaHMGB1 and AaRel1A. Notably, DNA bending by AaHMGB1
      enhanced the binding of AaRel1A to a DNA fragment containing a putative NF-kB/Rel
      response element. Importantly, AaHMGB1 was identified as a potential immune
      modulator in A. aegypti through AaHMGB1 overexpression or RNAi silencing in Aag-2
      cells followed by bacterial challenge or through AaHMGB1 RNAi knockdown in
      mosquitoes followed by Dengue virus (DENV) infection. We propose a model in which
      AaHMGB1 bends NF-kB/Rel target DNA to recruit and allow more efficient AaRel1A
      binding to activate transcription of effector genes, culminating in a stronger
      Toll pathway-mediated response against DENV infection.

PMID- 27867078
TI  - Co-expression of two heterologous lactate dehydrogenases genes in Kluyveromyces
      marxianus for l-lactic acid production.
AB  - Lactic acid (LA) is a versatile compound used in the food, pharmaceutical,
      textile, leather, and chemical industries. Biological production of LA is
      possible by yeast strains expressing a bacterial gene encoding l-lactate
      dehydrogenase (LDH). Kluyveromyces marxianus is an emerging non-conventional
      yeast with various phenotypes of industrial interest. However, it has not been
      extensively studied for LA production. In this study, K. marxianus was engineered
      to express and co-express various heterologous LDH enzymes that were reported to
      have different pH optimums. Specifically, three LDH enzymes originating from
      Staphylococcus epidermidis (SeLDH; optimal at pH 5.6), Lactobacillus acidophilus
      (LaLDH; optimal at pH 5.3), and Bos taurus (BtLDH; optimal at pH 9.8) were
      functionally expressed individually and in combination in K. marxianus, and the
      resulting strains were compared in terms of LA production. A strain co-expressing
      SeLDH and LaLDH (KM5 La+SeLDH) produced 16.0g/L LA, whereas the strains
      expressing those enzymes individually produced only 8.4 and 6.8g/L, respectively.
      This co-expressing strain produced 24.0g/L LA with a yield of 0.48g/g glucose in
      the presence of CaCO3. Our results suggest that co-expression of LDH enzymes with
      different pH optimums provides sufficient LDH activity under dynamic
      intracellular pH conditions, leading to enhanced production of LA compared to
      individual expression of the LDH enzymes.

PMID- 27867077
TI  - Critical phases of viral production processes monitored by capacitance.
AB  - Over the last decade industrial manufacturing of viral vaccines and viral vectors
      for prophylactic and therapeutic applications is experiencing a remarkable
      growth. Currently, the quality attributes of viral derived products are assessed
      only at the end-point of the production process, essentially because in-process
      monitoring tools are not available or not implemented at industrial scale.
      However, to demonstrate process reproducibility and robustness, manufacturers are
      strongly advised by regulatory agencies to adopt more on-line process monitoring
      and control. Dielectric spectroscopy has been successfully used as an excellent
      indicator of the cell culture state in mammalian and yeast cell systems. We
      previously reported the use of this technique for monitoring influenza and
      lentiviral productions in HEK293 cell cultures. For both viruses, multi-frequency
      capacitance measurements allowed not only the on-line monitoring of the
      production kinetics, but also the identification of the viral release time from
      the cells. The present study demonstrates that the same approach can be
      successfully exploited for the on-line monitoring of different enveloped and non
      enveloped virus production kinetics in cell culture processes. The on-line
      monitoring multi-frequency capacitance method was assessed in human HEK293 and
      Sf9 insect cells expression systems, with viral productions initiated by either
      infection or transfection. The comparative analyses of all the data acquired
      indicate that the characteristic capacitance signals were highly correlated with
      the occurrence of viral replication phases. Furthermore the evolution of the cell
      dielectric properties (intracellular conductivity and membrane capacitance) were
      indicative of each main replication steps. In conclusion, multi-frequency
      capacitance has a great potential for on-line monitoring, supervision and control
      of viral vector production in cell culture processes.

PMID- 27867079
TI  - Variability in diagnostic error rates of 10 MRI centers performing lumbar spine
      MRI examinations on the same patient within a 3-week period.
AB  - BACKGROUND CONTEXT: In today's health-care climate, magnetic resonance imaging
      (MRI) is often perceived as a commodity-a service where there are no meaningful
      differences in quality and thus an area in which patients can be advised to
      select a provider based on price and convenience alone. If this prevailing view
      is correct, then a patient should expect to receive the same radiological
      diagnosis regardless of which imaging center he or she visits, or which
      radiologist reviews the examination. Based on their extensive clinical
      experience, the authors believe that this assumption is not correct and that it
      can negatively impact patient care, outcomes, and costs. PURPOSE: This study is
      designed to test the authors' hypothesis that radiologists' reports from multiple
      imaging centers performing a lumbar MRI examination on the same patient over a
      short period of time will have (1) marked variability in interpretive findings
      and (2) a broad range of interpretive errors. STUDY DESIGN: This is a prospective
      observational study comparing the interpretive findings reported for one patient
      scanned at 10 different MRI centers over a period of 3 weeks to each other and to
      reference MRI examinations performed immediately preceding and following the 10
      MRI examinations. PATIENT SAMPLE: The sample is a 63-year-old woman with a
      history of low back pain and right L5 radicular symptoms. OUTCOME MEASURES:
      Variability was quantified using percent agreement rates and Fleiss kappa
      statistic. Interpretive errors were quantified using true-positive counts, false
      positive counts, false-negative counts, true-positive rate (sensitivity), and
      false-negative rate (miss rate). METHODS: Interpretive findings from 10 study MRI
      examinations were tabulated and compared for variability and errors. Two of the
      authors, both subspecialist spine radiologists from different institutions,
      independently reviewed the reference examinations and then came to a final
      diagnosis by consensus. Errors of interpretation in the study examinations were
      considered present if a finding present or not present in the study examination's
      report was not present in the reference examinations. RESULTS: Across all 10
      study examinations, there were 49 distinct findings reported related to the
      presence of a distinct pathology at a specific motion segment. Zero interpretive
      findings were reported in all 10 study examinations and only one finding was
      reported in nine out of 10 study examinations. Of the interpretive findings,
      32.7% appeared only once across all 10 of the study examinations' reports. A
      global Fleiss kappa statistic, computed across all reported findings, was 0.20+/
      0.06, indicating poor overall agreement on interpretive findings. The average
      interpretive error count in the study examinations was 12.5+/-3.2 (both false
      positives and false-negatives). The average false-negative count per examination
      was 10.9+/-2.9 out of 25 and the average false-positive count was 1.6+/-0.9,
      which correspond to an average true-positive rate (sensitivity) of 56.4%+/-11.7
      and miss rate of 43.6%+/-11.7. CONCLUSIONS: This study found marked variability
      in the reported interpretive findings and a high prevalence of interpretive
      errors in radiologists' reports of an MRI examination of the lumbar spine
      performed on the same patient at 10 different MRI centers over a short time
      period. As a result, the authors conclude that where a patient obtains his or her
      MRI examination and which radiologist interprets the examination may have a
      direct impact on radiological diagnosis, subsequent choice of treatment, and
      clinical outcome.

PMID- 27867081
TI  - Defining the number and type of fixation anchors for optimal main curve
      correction in posterior surgery for adolescent idiopathic scoliosis.
AB  - BACKGROUND CONTEXT: The number and type of fixation anchors to use during
      posterior surgery for adolescent idiopathic scoliosis (AIS) is still debated, and
      the relationship with curve correction remains unclear. PURPOSE: This study aimed
      to determine the number and type of fixation anchors associated with optimal
      curve correction following posterior surgery for AIS. STUDY DESIGN: A
      retrospective study of the relationship between fixation anchors and main curve
      correction in AIS surgery was carried out. PATIENT SAMPLE: A cohort of 137 AIS
      patients operated from a posterior-only approach using hooks and pedicle screws
      comprised the study sample. OUTCOME MEASURES: Correction of the main scoliotic
      curve was the outcome measure. METHODS: Implant density (ID) was defined as the
      number of fixation anchors divided by the number of available anchor sites within
      the main curve. Pedicle screw ratio (PSR) was defined as the number of pedicle
      screws divided by the total number of fixation anchors within the main curve.
      Multiple linear regressions were performed to analyze the influence of ID and PSR
      on main curve correction, while taking into account age, gender, curve type,
      preoperative main Cobb angle, main curve reducibility, number of fused levels,
      and number of levels within the main curve. RESULTS: Main coronal curve
      correction was significantly related only to ID for all patients and for the
      subgroup of patients with a main thoracic curve. Constructs with an ID >=70% and
      <90% provided a correction similar to that obtained with an ID >=90%. However,
      main coronal curve correction was inferior for constructs with an ID <70%, when
      compared with constructs with ID >=90%. Implant density and PSR were not related
      to the change in thoracic kyphosis in the multiple linear regressions.
      CONCLUSIONS: Implant density is an important predictor of main coronal curve
      correction in posterior surgery for AIS. Increasing the number of fixation
      anchors within the main curve-rather than favoring screws over hooks-can lead to
      better correction in the coronal plane. However, after reaching an ID of >=70% in
      the main curve, adding fixation anchors is not likely to result in significantly
      greater correction of the main curve in the coronal plane.

PMID- 27867080
TI  - Biomechanical advantages of robot-assisted pedicle screw fixation in posterior
      lumbar interbody fusion compared with freehand technique in a prospective
      randomized controlled trial-perspective for patient-specific finite element
      analysis.
AB  - BACKGROUND CONTEXT: There have been conflicting results on the surgical outcome
      of lumbar fusion surgery using two different techniques: robot-assisted pedicle
      screw fixation and conventional freehand technique. In addition, there have been
      no studies about the biomechanical issues between both techniques. PURPOSE: This
      study aimed to investigate the biomechanical properties in terms of stress at
      adjacent segments using robot-assisted pedicle screw insertion technique (robot
      assisted, minimally invasive posterior lumbar interbody fusion, Rom-PLIF) and
      freehand technique (conventional, freehand, open approach, posterior lumbar
      interbody fusion, Cop-PLIF) for instrumented lumbar fusion surgery. STUDY DESIGN:
      This is an additional post-hoc analysis for patient-specific finite element (FE)
      model. PATIENT SAMPLE: The sample is composed of patients with degenerative
      lumbar disease. OUTCOME MEASURES: Intradiscal pressure and facet contact force
      are the outcome measures. METHODS: Patients were randomly assigned to undergo an
      instrumented PLIF procedure using a Rom-PLIF (37 patients) or a Cop-PLIF (41),
      respectively. Five patients in each group were selected using a simple random
      sampling method after operation, and 10 preoperative and postoperative lumbar
      spines were modeled from preoperative high-resolution computed tomography of 10
      patients using the same method for a validated lumbar spine model. Under four
      pure moments of 7.5 Nm, the changes in intradiscal pressure and facet joint
      contact force at the proximal adjacent segment following fusion surgery were
      analyzed and compared with preoperative states. RESULTS: The representativeness
      of random samples was verified. Both groups showed significant increases in
      postoperative intradiscal pressure at the proximal adjacent segment under four
      moments, compared with the preoperative state. The Cop-PLIF models demonstrated
      significantly higher percent increments of intradiscal pressure at proximal
      adjacent segments under extension, lateral bending, and torsion moments than the
      Rom-PLIF models (p=.032, p=.008, and p=.016, respectively). Furthermore, the
      percent increment of facet contact force was significantly higher in the Cop-PLIF
      models under extension and torsion moments than in the Rom-PLIF models (p=.016
      under both extension and torsion moments). CONCLUSIONS: The present study showed
      the clinical application of subject-specific FE analysis in the spine. Even
      though there was biomechanical superiority of the robot-assisted insertions in
      terms of alleviation of stress increments at adjacent segments after fusion,
      cautious interpretation is needed because of the small sample size.

PMID- 27867082
TI  - Erratum to "BCGitis in children".

PMID- 27867083
TI  - Trends in antimicrobial resistance among Bacteroides species and Parabacteroides
      species in the United States from 2010-2012 with comparison to 2008-2009.
AB  - The susceptibility trends for Bacteroides fragilis and related species against
      various antibiotics were determined using data from 3 years of surveillance (2010
      2012) on 779 isolates referred by 7 medical centers. The antibiotic test panel
      included imipenem, ertapenem, meropenem, ampicillin-sulbactam, piperacillin
      tazobactam, cefoxitin, clindamycin, moxifloxacin, tigecycline, linezolid,
      chloramphenicol and . MICs were determined using the agar dilution CLSI reference
      method. Carbapenem resistance remained low (range 1.1%-2.5%) and unchanged from
      2008 to 9 through 2010-2012. Resistance also remained low to the beta-lactam/beta
      lactamase inhibitor combinations (1.1%-4.4%). While resistance to clindamycin and
      moxifloxacin remained high; rates were lower for B. fragilis in 2010-12 (24% and
      19% respectively) compared to the earlier time frame of 2008-9 (29% and 35%
      respectively for the earlier time frame). There were notable species and
      resistance associations which have been demonstrated previously. No resistance to
      metronidazole or chloramphenicol resistance was seen. These data demonstrate the
      continued variability in resistance among Bacteroides and Parabacteroides
      species, but do demonstrate that carbapenems and beta-lactam/beta-lactamase
      inhibitor combinations remain very active throughout the United States.

PMID- 27867084
TI  - New concepts in asthma: clinical phenotypes and pathophysiological mechanisms.
AB  - Asthma is among the most common chronic inflammatory diseases worldwide. Recent
      evidence indicates that the pathogenesis shows a high degree of heterogeneity.
      Patient subsets have been identified that exhibit different cellular and
      molecular patterns of dysregulation. A prominent example is eosinophilic Th2
      driven asthma. These unique and molecular patterns are termed endotypes.
      Characterization of endotypes has broad implications for therapeutic
      interventions. Although ~80% of asthmatic patients respond well to standard anti
      inflammatory therapies, the remaining subset particularly consisting of severe
      patients requires a more specialized endotype-specific approach. This
      interrelationship between clinical phenotypes, molecular endotypes and endotype
      specific therapies is the focus of this review.

PMID- 27867085
TI  - Optically active stereoisomers of 5-(1-iodoethyl)-4-(4'
      isopropylphenyl)dihydrofuran-2-one: The effect of the configuration of
      stereocenters on apoptosis induction in canine cancer cell lines.
AB  - Four stereoisomers of delta-iodo-gamma-lactones with p-isopropylphenyl
      substituent at beta-position: cis-(4R,5R,6S)-1, cis-(4S,5S,6R)-2, trans
      (4R,5S,6R)-3, trans-(4S,5R,6S)-4 with proved antiproliferative activity were
      subjected to in vitro tests for a better understanding of their anticancer
      activity. The subject of our interest was a possible relationship between a
      configuration of chiral centers of the studied lactones and their anticancer
      potency against a panel of canine cell lines representing hematopoietic (CLBL-1,
      GL-1, CL-1, CLB70) and mammary gland cancers (P114, CMT-U27, CMT-U309). To
      determine the anticancer activity of the tested compounds, cell viability and
      cell metabolic activity were checked using propidium iodide staining and the MTT
      test. To determine whether the studied compounds cause necrotic or apoptotic cell
      death, two assays for apoptosis evaluation were performed, annexin V staining and
      detection of caspase 3/7 activation. Simultaneously, the effects of the compounds
      on the cell cycle were also examined. The conducted research confirmed the
      anticancer potential of the tested lactones against canine cancers. The
      investigated isomers exerted higher activity against canine lymphoma/leukemia
      cell lines than against mammary tumors, whereas the configuration of stereogenic
      centers of the examined compounds affected their activity. It has been shown that
      stereoisomers with 4S configuration (2,4) were more active, and the most potent
      one was the cis-(4S,5S,6R)-2 isomer. The investigated lactones seemed to initiate
      the process of apoptosis rather than acting as typical cytostatic agents, as cell
      death via apoptosis, and no increase in G2-M population in the cell cycle
      analysis were observed. The presented study demonstrated that all four
      stereoisomers of delta-iodo-gamma-lactones with p-isopropylphenyl substituent at
      beta-position induced apoptosis via a mitochondrial-mediated, caspase-dependent
      pathway.

PMID- 27867086
TI  - Diazoxide prevents reactive oxygen species and mitochondrial damage, leading to
      anti-hypertrophic effects.
AB  - Pathological cardiac hypertrophy is characterized by wall thickening or chamber
      enlargement of the heart in response to pressure or volume overload,
      respectively. This condition will, initially, improve the organ contractile
      function, but if sustained will render dysfunctional mitochondria and oxidative
      stress. Mitochondrial ATP-sensitive K+ channels (mitoKATP) modulate the redox
      status of the cell and protect against several cardiac insults. Here, we tested
      the hypothesis that mitoKATP opening (using diazoxide) will avoid isoproterenol
      induced cardiac hypertrophy in vivo by decreasing reactive oxygen species (ROS)
      production and mitochondrial Ca2+-induced swelling. To induce cardiac
      hypertrophy, Swiss mice were treated intraperitoneally with isoproterenol (30
      mg/kg/day) for 8 days. Diazoxide (5 mg/kg/day) was used to open mitoKATP and 5
      hydroxydecanoate (5 mg/kg/day) was administrated as a mitoKATP blocker.
      Isoproterenol-treated mice had elevated heart weight/tibia length ratios and
      increased myocyte cross-sectional areas. Additionally, hypertrophic hearts
      produced higher levels of H2O2 and had lower glutathione peroxidase activity. In
      contrast, mitoKATP opening with diazoxide blocked all isoproterenol effects in a
      manner reversed by 5-hydroxydecanoate. Isolated mitochondria from Isoproterenol
      induced hypertrophic hearts had increased susceptibility to Ca2+-induced swelling
      secondary to mitochondrial permeability transition pore opening. MitokATP opening
      was accompanied by lower Ca2+-induced mitochondrial swelling, an effect blocked
      by 5-hydroxydecanoate. Our results suggest that mitoKATP opening negatively
      regulates cardiac hypertrophy by avoiding oxidative impairment and mitochondrial
      damage.

PMID- 27867087
TI  - A quantitative immunoassay for lung cancer biomarker CIZ1b in patient plasma.
AB  - OBJECTIVES: Non-invasive tests for early detection of lung cancer are an
      important unmet clinical need. CIZ1b plasma biomarker can discriminate stage 1
      lung cancer from within high-risk groups with clinically useful accuracy, with
      ROC AUCs in excess of 0.9 for two independent retrospective cohorts, and could
      therefore meet this need. Our aim was to characterise the native state of the
      biomarker and develop a quantitative immunoassay. DESIGN AND METHODS: Selective
      denaturation, preparative electrophoresis and mass spectrometry of human plasma
      were used to characterise the biomarker and interaction partners. A sandwich
      ELISA was generated, and specificity for CIZ1b biomarker tested on lung cancer
      patient plasma. RESULTS: CIZ1b biomarker is a denaturation-resistant complex
      between a C-terminal fragment of CIZ1 bearing the CIZ1b epitope specified by
      alternative splicing of exon14, and fibrinogen alpha chain. Reconstitution of the
      biomarker epitope with purified fibrinogen and CIZ1b, but not CIZ1a (non
      alternatively spliced exon 14) confirmed the specificity of the results. The
      endogenous complex is highly stable in lung cancer plasma and can be quantified
      by pairing of a CIZ1b exon-junction specific antibody with detection of
      fibrinogen. Application of this sandwich ELISA to a prospectively collected
      development set of plasmas reveals the same level of accuracy as the western blot
      used to validate the discriminatory capability of the biomarker. CONCLUSIONS:
      Unexpected and unusual molecular structure of CIZ1b in native plasma has
      complicated immunoassay design, and delayed translation of this promising
      biomarker. However, CIZ1b can now be measured using a high-throughput, hospital
      friendly sandwich ELISA format, overcoming an important barrier to further
      clinical development and application of this blood test for early stage lung
      cancer.

PMID- 27867088
TI  - Techniques for blood volume fMRI with VASO: From low-resolution mapping towards
      sub-millimeter layer-dependent applications.
AB  - Quantitative cerebral blood volume (CBV) fMRI has the potential to overcome
      several specific limitations of BOLD fMRI. It provides direct physiological
      interpretability and promises superior localization specificity in applications
      of sub-millimeter resolution fMRI applications at ultra-high magnetic fields (7T
      and higher). Non-invasive CBV fMRI using VASO (vascular space occupancy),
      however, is inherently limited with respect to its data acquisition efficiency,
      restricting its imaging coverage and achievable spatial and temporal resolution.
      This limitation may be reduced with recent advanced acceleration and
      reconstruction strategies that allow two-dimensional acceleration, such as in
      simultaneous multi-slice (SMS) 2D-EPI or 3D-EPI in combination with CAIPIRINHA
      field-of-view shifting. In this study, we sought to determine the functional
      sensitivity and specificity of these readout strategies with VASO over a broad
      range of spatial resolutions; spanning from low spatial resolution (3mm) whole
      cortex to sub-millimeter (0.75mm) slab-of-cortex (for cortical layer-dependent
      applications). In the thermal-noise-dominated regime of sub-millimeter
      resolutions, 3D-EPI-VASO provides higher temporal stability and sensitivity to
      detect changes in CBV compared to 2D-EPI-VASO. In this regime, 3D-EPI-VASO
      unveils task activation located in the cortical laminae with little contamination
      from surface veins, in contrast to the cortical surface weighting of GE-BOLD
      fMRI. In the physiological-noise-dominated regime of lower resolutions, however,
      2D-SMS-VASO shows superior performance compared to 3D-EPI-VASO. Due to its
      superior sensitivity at a layer-dependent level, 3D-EPI VASO promises to play an
      important role in future neuroscientific applications of layer-dependent fMRI.

PMID- 27867089
TI  - Clinical vascular imaging in the brain at 7T.
AB  - Stroke and related cerebrovascular diseases are a major cause of mortality and
      disability. Even at standard-field-strengths (1.5T), MRI is by far the most
      sensitive imaging technique to detect acute brain infarctions and to characterize
      incidental cerebrovascular lesions, such as white matter hyperintensities,
      lacunes and microbleeds. Arterial time-of-flight (TOF) MR angiography (MRA) can
      depict luminal narrowing or occlusion of the major brain feeding arteries, and
      this without the need for contrast administration. Compared to 1.5T MRA, the use
      of high-field strength (3T) and even more so ultra-high-field strengths (7T),
      enables the visualization of the lumen of much smaller intracranial vessels,
      while adding a contrast agent to TOF MRA at 7T may enable the visualization of
      even more distal arteries in addition to veins and venules. Moreover, with 3T and
      7T, the arterial vessel walls beyond the circle of Willis become visible with
      high-resolution vessel wall imaging. In addition, with 7T MRI, the brain
      parenchyma can now be visualized on a submillimeter scale. As a result, high
      resolution imaging studies of the brain and its blood supply at 7T have generated
      new concepts of different cerebrovascular diseases. In the current article, we
      will discuss emerging clinical applications and future directions of vascular
      imaging in the brain at 7T MRI.

PMID- 27867090
TI  - Visual cortex responses reflect temporal structure of continuous quasi-rhythmic
      sensory stimulation.
AB  - Neural processing of dynamic continuous visual input, and cognitive influences
      thereon, are frequently studied in paradigms employing strictly rhythmic
      stimulation. However, the temporal structure of natural stimuli is hardly ever
      fully rhythmic but possesses certain spectral bandwidths (e.g. lip movements in
      speech, gestures). Examining periodic brain responses elicited by strictly
      rhythmic stimulation might thus represent ideal, yet isolated cases. Here, we
      tested how the visual system reflects quasi-rhythmic stimulation with frequencies
      continuously varying within ranges of classical theta (4-7Hz), alpha (8-13Hz) and
      beta bands (14-20Hz) using EEG. Our findings substantiate a systematic and
      sustained neural phase-locking to stimulation in all three frequency ranges.
      Further, we found that allocation of spatial attention enhances EEG-stimulus
      locking to theta- and alpha-band stimulation. Our results bridge recent findings
      regarding phase locking ("entrainment") to quasi-rhythmic visual input and
      "frequency-tagging" experiments employing strictly rhythmic stimulation. We
      propose that sustained EEG-stimulus locking can be considered as a continuous
      neural signature of processing dynamic sensory input in early visual cortices.
      Accordingly, EEG-stimulus locking serves to trace the temporal evolution of
      rhythmic as well as quasi-rhythmic visual input and is subject to attentional
      bias.

PMID- 27867092
TI  - Peptide-rich venom from the spider Heteropoda venatoria potently inhibits insect
      voltage-gated sodium channels.
AB  - Heteropoda venatoria is a venomous spider species distributed worldwide and has a
      characteristic habit of feeding on insects. Reverse-phase high-performance liquid
      chromatography and matrix-assisted laser-desorption/ionization time-of-flight
      mass spectrometry analyses revealed that H. venatoria venom contains hundreds of
      peptides with a predominant molecular weights of 3000-5000 Da. Intra-abdominal
      injection of the venom had severe toxic effects on cockroaches and caused death
      at higher concentrations. The LD50 was 28.18 MUg/g of body weight in the
      cockroach. It was found that the venom had potent inhibitory effect on voltage
      gated sodium channels (VGSCs) in Periplaneta americana cockroach dorsal unpaired
      median (DUM) neurons with an IC50 values of 6.25 +/- 0.02 MUg/mL. However, 100
      MUg/mL venom only partially blocked VGSC currents in rat dorsal root ganglion
      cells, a much lower inhibitory effect than that on DUM VGSCs. Our results
      indicate that the venom of H. venatoria contains diverse neurotoxins that might
      become new leads for bioinsecticides.

PMID- 27867091
TI  - Development and aging of a brain neural stem cell niche.
AB  - In the anterior forebrain, along the lateral wall of the lateral ventricles, a
      neurogenic stem cell niche is found in a region referred to as the ventricular
      subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new
      neurons to the olfactory bulb throughout adulthood; however, with increasing age
      stem cell numbers are reduced and neurogenic capacity is significantly
      diminished, but new olfactory bulb neurons continue to be produced even in old
      age. Humans, in contrast, show little to no new neurogenesis after two years of
      age and whether V-SVZ neural stem cells persist in the adult human brain remains
      unclear. Here, we review functional and organizational differences in the V-SVZ
      stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche
      and its associated functions.

PMID- 27867093
TI  - Relationship between food and venom production in the estuarine stonefish
      Synanceia horrida.
AB  - BACKGROUND: The potential costs of venom production may be significant to many
      marine venomous taxa. In general, the parameters that influence the rate of venom
      production are poorly understood, but seem to be related to feeding frequency.
      METHODS: This study examines the effects of starvation on venom profile and venom
      yield on the estuarine stonefish (Synanceia horrida). In total, the venom of
      eight stonefishes was tested under two feeding regimes. Over a four week period,
      one of the two groups underwent an episode of suspended feeding, while the other
      was fed on a daily basis. The effect of time on venom replacement was determined
      by a paired T-test. ANOVA was performed to analyze differences in venom weight
      between fed and unfed treatments. RESULTS: Nutritional suspension was found to
      have a significant effect on the quantity of venom produced. SDS-PAGE gel and
      FPLC revealed that the components of the venom collected from both groups were
      similar, indicating that four weeks is an adequate time to regenerate key venom
      components but not replenish initial venom quantities. CONCLUSIONS: Venom
      production was found to be affected by starvation.

PMID- 27867094
TI  - Differences between renal effects of venom from two Bothrops jararaca populations
      from southeastern and southern Brazil.
AB  - Components from animal venoms may vary according to the snake's age, gender and
      region of origin. Recently, we performed a proteomic analysis of Bothrops
      jararaca venom from southern (BjSv) and southeastern (BjSEv) Brazil, showing
      differences in the venom composition, as well as its biological activity. To
      continue the study, we report in this short communication the different effects
      induced by the BjSEv and BjSv on isolated kidney and MDCK renal cells. BjSEv
      decreased perfusion pressure (PP) and renal vascular resistance (RVR) and
      increased urinary flow (UF) and glomerular filtration rate (GFR), while BjSv did
      not alter PP and RVR and reduced UF and GFR. Both types of venom, more
      expressively BjSEv, reduced %TNa+, %TK+ and %Cl-. In MDCK cells, the two types of
      venom showed cytotoxicity with IC50 of 1.22 MUg/mL for BjSv and 1.18 MUg/mL for
      BjSEv and caused different profiles of cell death, with BjSv being more necrotic.
      In conclusion, we suggest that BjSv is more nephrotoxic than BjSEv.

PMID- 27867095
TI  - Identification of snake venom allergens by two-dimensional electrophoresis
      followed by immunoblotting.
AB  - This allergic reaction to snake venom was described to occur in patients after
      recurrent exposure through bites in amateur and professional snake handlers,
      which might be underestimated and contribute to fatal snakebites in victim,
      independently from the toxicity of the venom itself. Few allergens were
      identified from snake venoms by normal SDS-PAGE, which cannot separate the snake
      venom completely. In the present study, we identified nine potential allergens by
      two-dimensional (2D) electrophoresis followed by immunoblotting (named as
      allergenomics) in Protobothrops mucrosquamatus venom. By multidimensional liquid
      chromatography-ion trap mass spectrometry (MDLC-ESI-LTQ-MS/MS) analysis, six
      allergens showed sequence similarity to snake venom serine proteinases. Other
      allergens showed sequence similarity to snake venom metalloproteinase. These
      allergic reactions to snake venom allergens might contribute to fatal snakebites
      in victim, independently.

PMID- 27867096
TI  - Ptgr1 expression is regulated by NRF2 in rat hepatocarcinogenesis and promotes
      cell proliferation and resistance to oxidative stress.
AB  - Prostaglandin reductase-1 (Ptgr1) is an alkenal/one oxidoreductase that is
      involved in the catabolism of eicosanoids and lipid peroxidation such as 4
      hydroxynonenal (4-HNE). Recently, we reported that Ptgr1 is overexpressed in
      human clinical and experimentally induced samples of hepatocellular carcinoma
      (HCC). However, how the expression of this gene is regulated and its role in
      carcinogenesis are not yet known. Here, we studied parameters associated with
      antioxidant responses and the mechanisms underlying the induction of Ptgr1
      expression by the activation of Nuclear Factor (erythroid-derived-2)-like-2
      (NRF2). For these experiments, we used two protocols of induced
      hepatocarcinogenesis in rats. Furthermore, we determined the effect of PTGR1 on
      cell proliferation and resistance to oxidative stress in cell cultures of the
      epithelial liver cell line, C9. Ptgr1 was overexpressed during the early phase in
      altered hepatocyte foci, and this high level of expression was maintained in
      persistent nodules until tumors developed. Ptgr1 expression was regulated by
      NRF2, which bound to an antioxidant response element at -653bp in the rat Ptgr1
      gene. The activation of NRF2 induced the activation of an antioxidant response
      that included effects on proteins such as glutamate-cysteine ligase, catalytic
      subunit, NAD(P)H dehydrogenase quinone-1 (NQO1) and glutathione-S-transferase-P
      (GSTP1). These effects may have produced a reduced status that was associated
      with a high proliferation rate in experimental tumors. Indeed, when Ptgr1 was
      stably expressed, we observed a reduction in the time required for proliferation
      and a protective effect against hydrogen peroxide- and 4-HNE-induced cell death.
      These data were consistent with data showing colocalization between PTGR1 and 4
      HNE protein adducts in liver nodules. These findings suggest that Ptgr1 and
      antioxidant responses act as a metabolic adaptation and could contribute to
      proliferation and cell-death evasion in liver tumor cells. Furthermore, these
      data indicate that Ptgr1 could be used to design early diagnostic tools or
      targeted therapies for HCC.

PMID- 27867097
TI  - Mitochondrial remodeling in the liver following chronic alcohol feeding to rats.
AB  - The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to
      cause declines in mitochondrial respiration (state III), decreased expression of
      respiratory complexes, and decreased respiratory control ratios (RCR) in liver
      mitochondria. These declines and other mitochondrial alterations have led to the
      hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver.
      If oral alcohol feeding leads to mitochondrial dysfunction, one would predict
      that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats
      would cause greater declines in mitochondrial bioenergetics in the liver. In this
      study, we examined the mitochondrial alterations that occur in rats fed alcohol
      both orally and intragastrically. Oral alcohol feeding decreased glutamate/malate
      , acetaldehyde- and succinate-driven state III respiration, RCR, and expression
      of respiratory complexes (I, III, IV, V) in liver mitochondria, in agreement with
      previous results. IG alcohol feeding, on the other hand, caused a slight increase
      in glutamate/malate-driven respiration, and significantly increased acetaldehyde
      driven respiration in liver mitochondria. IG feeding also caused liver
      mitochondria to experience a decline in succinate-driven respiration, but these
      decreases were smaller than those observed with oral alcohol feeding.
      Surprisingly, oral and IG alcohol feeding to rats increased mitochondrial
      respiration using other substrates, including glycerol-3-phosphate (which
      delivers electrons from cytoplasmic NADH to mitochondria) and octanoate (a
      substrate for beta-oxidation). The enhancement of glycerol-3-phosphate- and
      octanoate-driven respiration suggests that liver mitochondria remodeled in
      response to alcohol feeding. In support of this notion, we observed that IG
      alcohol feeding also increased expression of mitochondrial glycerol phosphate
      dehydrogenase-2 (GPD2), transcription factor A (TFAM), and increased
      mitochondrial NAD+-NADH and NADP+-NADPH levels in the liver. Our findings suggest
      that mitochondrial dysfunction represents an incomplete picture of mitochondrial
      dynamics that occur in the liver following alcohol feeding. While alcohol feeding
      causes some mitochondrial dysfunction (i.e. succinate-driven respiration), our
      work suggests that the major consequence of alcohol feeding is mitochondrial
      remodeling in the liver as an adaptation. This mitochondrial remodeling may play
      an important role in the enhanced alcohol metabolism and other adaptations in the
      liver that develop with alcohol intake.

PMID- 27867100
TI  - The independent influence of concussive and sub-concussive impacts on soccer
      players' neurophysiological and neuropsychological function.
AB  - Accumulating research demonstrates that repetitive sub-concussive impacts can
      alter the structure, function and connectivity of the brain. However, the
      functional significance of these alterations as well as the independent
      contribution of concussive and sub-concussive impacts to neurophysiological and
      neuropsychological health are unclear. Accordingly, we compared the
      neurophysiological and neuropsychological function of contact athletes with
      (concussion group) and without (sub-concussion group) a history of concussion, to
      non-contact athletes. We evaluated event-related brain potentials (ERPs) elicited
      during an oddball task and performance on a targeted battery of
      neuropsychological tasks. Athletes in the sub-concussion and concussion groups
      exhibited similar amplitude reductions in the ERP indices of attentional resource
      allocation (P3b) and attentional orienting (P3a) relative to non-contact
      athletes. However, only athletes in the concussion group exhibited reduced
      amplitude in the ERP index of perceptual attention (N1). Athletes in the sub
      concussion and concussion groups also exhibited deficits in memory recall
      relative to non-contact athletes, but athletes in the concussion group also
      exhibited significantly more recall errors than athletes in the sub-concussion
      group. Additionally, only athletes in the concussion group exhibited response
      delays during the oddball task. The current findings suggest that sub-concussive
      impacts are associated with alterations in the neurophysiological and
      neuropsychological indices of essential cognitive functions, albeit to a lesser
      degree than the combination of sub-concussive and concussive impacts.

PMID- 27867098
TI  - Ammonia promotes endothelial cell survival via the heme oxygenase-1-mediated
      release of carbon monoxide.
AB  - Although endothelial cells produce substantial quantities of ammonia during cell
      metabolism, the physiologic role of this gas in these cells is not known. In this
      study, we investigated if ammonia regulates the expression of heme oxygenase-1
      (HO-1), and if this enzyme influences the biological actions of ammonia on
      endothelial cells. Exogenously administered ammonia, given as ammonium chloride
      or ammonium hydroxide, or endogenously generated ammonia stimulated HO-1 protein
      expression in cultured human and murine endothelial cells. Dietary
      supplementation of ammonia also induced HO-1 protein expression in murine
      arteries. The increase in HO-1 protein by ammonia in endothelial cells was first
      detected 4h after ammonia exposure and was associated with the induction of HO-1
      mRNA, enhanced production of reactive oxygen species (ROS), and increased
      expression and activity of NF-E2-related factor-2 (Nrf2). Ammonia also activated
      the HO-1 promoter and this was blocked by mutating the antioxidant responsive
      element or by overexpressing dominant-negative Nrf2. The induction of HO-1
      expression by ammonia was dependent on ROS formation and prevented by N
      acetylcysteine or rotenone. Finally, prior treatment of endothelial cells with
      ammonia inhibited tumor necrosis factor-alpha-stimulated cell death. However,
      silencing HO-1 expression abrogated the protective action of ammonia and this was
      reversed by the administration of carbon monoxide but not bilirubin or iron. In
      conclusion, this study demonstrates that ammonia stimulates the expression of HO
      1 in endothelial cells via the ROS-Nrf2 pathway, and that the induction of HO-1
      contributes to the cytoprotective action of ammonia by generating carbon
      monoxide. Moreover, it identifies ammonia as a potentially important signaling
      gas in the vasculature that promotes endothelial cell survival.

PMID- 27867099
TI  - Risky repair: DNA-protein crosslinks formed by mitochondrial base excision DNA
      repair enzymes acting on free radical lesions.
AB  - Oxygen is both necessary and dangerous for aerobic cell function. ATP is most
      efficiently made by the electron transport chain, which requires oxygen as an
      electron acceptor. However, the presence of oxygen, and to some extent the
      respiratory chain itself, poses a danger to cellular components. Mitochondria,
      the sites of oxidative phosphorylation, have defense and repair pathways to cope
      with oxidative damage. For mitochondrial DNA, an essential pathway is base
      excision repair, which acts on a variety of small lesions. There are instances,
      however, in which attempted DNA repair results in more damage, such as the
      formation of a DNA-protein crosslink trapping the repair enzyme on the DNA. That
      is the case for mitochondrial DNA polymerase gamma acting on abasic sites
      oxidized at the 1-carbon of 2-deoxyribose. Such DNA-protein crosslinks presumably
      must be removed in order to restore function. In nuclear DNA, ubiquitylation of
      the crosslinked protein and digestion by the proteasome are essential first
      processing steps. How and whether such mechanisms operate on DNA-protein
      crosslinks in mitochondria remains to be seen.

PMID- 27867101
TI  - Regulation of fear extinction by long-term depression: The roles of
      endocannabinoids and brain derived neurotrophic factor.
AB  - The extinction of a conditioned fear response is of great interest in the search
      for a means of ameliorating adverse neurobiological changes resulting from
      stress. The discovery that endocannibinoid (EC) levels are inversely related to
      the extent of such stress, and that the amygdala is a primary site mediating
      stress, suggests that ECs in this brain region might play a major role in
      extinction. Supporting this are the observations that the basolateral complex of
      the amygdala shows an increase in ECs only during extinction and that early
      clinical trials indicate that cannabinoid-like agents, when taken orally by
      patients suffering from post traumatic stress disorder (PTSD), reduce insomnia
      and nightmares. In order to optimize the potential of these agents to ameliorate
      symptoms of PTSD four important questions need to be answered: first, what is the
      identity of the cells that release ECs in the amygdala during extinction; second,
      what are their sites of action; third, what roles do the ECs play in the
      alleviation of long- depression (LTD), a process central to extinction; and
      finally, to what extent does brain derived neurotrophic factor (BDNF) facilitate
      the release of ECs? A review of the relevant literature is presented in an
      attempt to answer these questions. It is suggested that the principal cell
      involved in EC synthesis and release during extinction is the so-called
      excitatory extinction neuron in the basal nucleus of the amygdala. Furthermore
      that the main site of action of the ECs is the adjacent calcitonin gene-related
      peptide inhibitory interneurons, whose normal role of blocking the excitatory
      neurons is greatly diminished. The molecular pathways leading (during extinction
      trials) to the synthesis and release of ECs from synaptic spines of extinction
      neurons, that is potentiated by BDNF, are also delineated in this review.
      Finally, consideration is given to how the autocrine action of BDNF, linked to
      the release of ECs, can lead to the sustained release of these, so maintaining
      extinction over long times.

PMID- 27867102
TI  - Neural correlates of response inhibition in current and former smokers.
AB  - Loss of behavioral control is a hallmark of addiction. Individual differences in
      basic cognitive processes such as response inhibition may be important for
      interrupting automatic behaviors associated with smoking and supporting prolonged
      abstinence. To examine how response inhibition and error monitoring processes
      differ as a function of smoking status, current smokers, former smokers and never
      smokers (N=126) completed a simple Go/No-Go task while undergoing functional
      magnetic resonance imaging. All groups performed similarly on the task and
      similarly engaged the inferior frontal gyrus and dorsal anterior cingulate
      cortex, regions traditionally associated with response inhibition and error
      monitoring, respectively. During response inhibition (i.e., Correct Rejects>Hits
      contrast), overall group differences emerged in the recruitment of the
      cerebellum, while individual group differences in error monitoring (False
      Alarms>Hits contrast) were seen for regions of the parietal lobe and thalamus
      (current smokers>former smokers), as well as regions of the bilateral cerebellum,
      parahippocampal gyrus and superior parietal lobe (i.e., ever smokers>never
      smokers). We discuss how our results replicate two previous large-sample studies
      that used the same Go/No-Go task and review these data in terms of network models
      of inhibitory and error monitoring abnormalities in addiction.

PMID- 27867103
TI  - Lymphoblastic lymphoma with a triple-hit profile: a rare but distinct and
      relevant entity.
AB  - Follicular lymphoma with progression to a high-grade lymphoma bears a poor
      prognosis. We describe a case of a 60-year-old man who presented in 2012 with an
      epidural mass, diagnosed as a diffuse large B-cell lymphoma (DLBCL) with
      concurrent low-grade follicular lymphoma. Three years later, the patient
      presented with a cervical mass, diagnosed as a lymphoblastic lymphoma (LBL). Both
      the DLBCL and LBL contained a "triple hit" with BCL2, BCL6, and cMYC
      translocations demonstrated by fluorescence in situ hybridization analysis and a
      complex karyotype by single-nucleotide polymorphism array analysis. Furthermore,
      the 2 lymphomas were shown to be clonally related by clonality analysis and
      single-nucleotide polymorphism array analysis. This case report presents a highly
      unusual case of an LBL with a triple hit, originating from a DLBCL, which has
      rarely been described in the literature and deserves further exploration.

PMID- 27867105
TI  - Arabidopsis NahG Plants as a Suitable and Efficient System for Transient
      Expression using Agrobacterium tumefaciens.

PMID- 27867104
TI  - Identification of transcripts involved in digestion, detoxification and immune
      response from transcriptome of Empoasca vitis (Hemiptera: Cicadellidae) nymphs.
AB  - Tea production has been significantly impacted by the false-eye leafhopper,
      Empoasca vitis (Gothe), around Asia. To identify the key genes which are
      responsible for nutrition absorption, xenobiotic metabolism and immune response,
      the transcriptome of either alimentary tracts or bodies minus alimentary tract of
      E. vitis was sequenced and analyzed. Over 31 million reads were obtained from
      Illumina sequencing. De novo sequence assembly resulted in 52,182 unigenes with a
      mean size of 848nt. The assembled unigenes were then annotated using various
      databases. Transcripts of at least 566 digestion-, 224 detoxification-, and 288
      immune-related putative genes in E. vitis were identified. In addition, relative
      expression of highly abundant transcripts was verified through quantitative real
      time PCR. Results from this investigation provide genomic information about E.
      vitis, which will be helpful in further study of E. vitis biology and in the
      development of novel strategies to control this devastating pest.

PMID- 27867106
TI  - The Mystery of Mendel's Stay-Green: Magnesium Stays Chelated in Chlorophylls.

PMID- 27867107
TI  - Draft Genome Sequence of Mentha longifolia and Development of Resources for Mint
      Cultivar Improvement.
AB  - The genus Mentha encompasses mint species cultivated for their essential oils,
      which are formulated into a vast array of consumer products. Desirable oil
      characteristics and resistance to the fungal disease Verticillium wilt are top
      priorities for the mint industry. However, cultivated mints have complex
      polyploid genomes and are sterile. Breeding efforts, therefore, require the
      development of genomic resources for fertile mint species. Here, we present draft
      de novo genome and plastome assemblies for a wilt-resistant South African
      accession of Mentha longifolia (L.) Huds., a diploid species ancestral to
      cultivated peppermint and spearmint. The 353 Mb genome contains 35 597 predicted
      protein-coding genes, including 292 disease resistance gene homologs, and nine
      genes determining essential oil characteristics. A genetic linkage map ordered
      1397 genome scaffolds on 12 pseudochromosomes. More than two million simple
      sequence repeats were identified, which will facilitate molecular marker
      development. The M. longifolia genome is a valuable resource for both metabolic
      engineering and molecular breeding. This is exemplified by employing the genome
      sequence to clone and functionally characterize the promoters in a peppermint
      cultivar, and demonstrating the utility of a glandular trichome-specific promoter
      to increase expression of a biosynthetic gene, thereby modulating essential oil
      composition.

PMID- 27867108
TI  - Poly (3,4-ethylenedioxythiophene) graphene oxide composite coatings for
      controlling magnesium implant corrosion.
AB  - : Magnesium (Mg) is a promising biodegradable implant material because of its
      appropriate mechanical properties and safe degradation products. However, in vivo
      corrosion speed and hydrogen gas production need to be controlled for uses in
      biomedical applications. Here we report the development of a conducting polymer
      3,4-ethylenedioxythiphene (PEDOT) and graphene oxide (GO) composite coating as a
      corrosion control layer. PEDOT/GO was electropolymerized on Mg samples in ethanol
      media. The coated Mg samples were subjected to various corrosion tests. The
      PEDOT/GO coating significantly reduced the rate of corrosion as evidenced by
      lower Mg ion concentration and pH of the corrosion media. In addition, the
      coating decreased the evolved hydrogen. Electrochemical analysis of the corroding
      samples showed more positive corrosion potential, a decreased corrosion current,
      and an increase in the polarization resistance. PEDOT/GO corrosion protection is
      attributed to three factors; an initial passive layer preventing solution
      ingress, buildup of negative charges in the film, and formation of corrosion
      protective Mg phosphate layer through redox coupling with Mg corrosion. To
      explore the biocompatibility of the coated implants in vitro, corrosion media
      from PEDOT/GO coated or uncoated Mg samples were exposed to cultured neurons
      where PEDOT/GO coated samples showed decreased toxicity. These results suggest
      that PEDOT/GO coating will be an effective treatment for controlling corrosion of
      Mg based medical implants. STATEMENT OF SIGNIFICANCE: Coating Mg substrates with
      a PEDOT/GO composite coating showed a significant decrease in corrosion rate.
      While conducting polymer coatings have been used to prevent corrosion on various
      metals, there has been little work on the use of these coatings for Mg.
      Additionally, to our knowledge, there has not been a report of the combined used
      of conducting polymer and GO as a corrosion control layer. Corrosion control is
      attributed to an initial barrier layer followed by electrochemical coupling of
      the PEDOT/GO coating with the substrate to facilitate the formation of a
      protective phosphate layer. This coupling also resulted in a decrease in hydrogen
      produced during corrosion, which could further improve the host tissue
      integration of Mg implants. This work elaborates on the potential for
      electroactive polymers to serve as corrosion control methods.

PMID- 27867109
TI  - Towards long lasting zirconia-based composites for dental implants:
      Transformation induced plasticity and its consequence on ceramic reliability.
AB  - : Zirconia-based composites were developed through an innovative processing route
      able to tune compositional and microstructural features very precisely. Fully
      dense ceria-stabilized zirconia ceramics (84vol% Ce-TZP) containing equiaxed
      alumina (8vol%Al2O3) and elongated strontium hexa-aluminate (8vol% SrAl12O19)
      second phases were obtained by conventional sintering. This work deals with the
      effect of the zirconia stabilization degree (CeO2 in the range 10.0-11.5mol%) on
      the transformability and mechanical properties of Ce-TZP-Al2O3-SrAl12O19
      materials. Vickers hardness, biaxial flexural strength and Single-edge V-notched
      beam tests revealed a strong influence of ceria content on the mechanical
      properties. Composites with 11.0mol% CeO2 or above exhibited the classical
      behaviour of brittle ceramics, with no apparent plasticity and very low strain to
      failure. On the contrary, composites with 10.5mol% CeO2 or less showed large
      transformation-induced plasticity and almost no dispersion in strength data.
      Materials with 10.5mol% of ceria showed the highest values in terms of biaxial
      bending strength (up to 1.1GPa) and fracture toughness (>10MPa?m). In these
      ceramics, as zirconia transformation precedes failure, the Weibull modulus was
      exceptionally high and reached a value of 60, which is in the range typically
      reported for metals. The results achieved demonstrate the high potential of using
      these new strong, tough and stable zirconia-based composites in structural
      biomedical applications. STATEMENT OF SIGNIFICANCE: Yttria-stabilized (Y-TZP)
      zirconia ceramics are increasingly used for developing metal-free restorations
      and dental implants. Despite their success related to their excellent mechanical
      resistance, Y-TZP can undergo Low Temperature Degradation which could be
      responsible for restoration damage or even worst the failure of the implant.
      Current research is focusing on strategies to improve the LTD resistance of Y-TZP
      or to develop alternative composites with better stability in vivo. In this work
      the mechanical characterization of a new type of very-stable zirconia-based
      composites is presented. These materials are composed of ceria-stabilized
      zirconia (84vol%Ce-TZP) containing two second phases (alpha-alumina and strontium
      hexa-aluminate) and exhibit exceptional strength, toughness and ductility, which
      may allow the processing of dental implants with a perfect reliability and longer
      lifetime.

PMID- 27867110
TI  - Poly(epsilon-benzyloxycarbonyl-L-lysine)-grafted branched polyethylenimine as
      efficient nanocarriers for indomethacin with enhanced oral bioavailability and
      anti-inflammatory efficacy.
AB  - : Star-block copolymers PEI-g-PZLL with a branched polyethylenimine (PEI) core
      and multiple grafted poly(epsilon-benzyloxycarbonyl-L-lysine) (PZLL) peripheral
      chains were designed, synthesized, and evaluated as nanocarriers for indomethacin
      (IND). In an aqueous solution, PEI-g-PZLL self-assembled into spherical
      nanoparticles capable of encapsulating IND at high loading capacity and loading
      efficiency. Differential scanning calorimetry and X-ray diffraction measurements
      indicated that IND was molecularly or amorphously dispersed in the nanoparticles.
      Fourier transform infrared spectra revealed the presence of multiple
      intermolecular interactions, including hydrogen bonding, electrostatic forces, pi
      pi stacking and hydrophobic interactions, between the block copolymer and the IND
      molecules. IND-loaded nanoparticles exhibited fast release under intestinal pH.
      Compared with raw IND, the utilization of PEI-g-PZLL as a carrier significantly
      enhanced the oral bioavailability of IND and improved its protective effect on
      renal ischemia-reperfusion injury, as evidenced by in vivo pharmacokinetic and
      pharmacodynamic studies. Cytotoxicity assay, histological observation and
      cellular uptake study suggested that PEI-g-PZLL was fairly biocompatible. All
      these results indicated that star-block copolymers PEI-g-PZLL could be used as
      efficient nanocarriers for IND and other poorly water-soluble drugs. STATEMENT OF
      SIGNIFICANCE: The use of polyethylenimine (PEI) as an oral drug delivery carrier
      is limited because it is not biodegradable and the use of higher molecular weight
      PEI leads to improved efficiency but also increased cytotoxicity. The design of
      functionalized PEIs with low cytotoxicity and high efficiency is crucial for
      developing a successful oral drug delivery system. In our study, poly(epsilon
      benzyloxycarbonyl-L-lysine) (PZLL)-grafted branched PEI (PEI-g-PZLL) was reported
      as an oral nanocarrier for indomethacin (IND). The low cytotoxicity and
      biodegradability, well-defined self-assembled nano-sized polymeric micelles, high
      loading capacity and loading efficiency, amorphous state of the encapsulated IND,
      as well as the enhanced oral bioavailability of IND, makes the copolymer PEI-g
      PZLL a promising nanocarrier for the oral administration of IND and possibly
      other poorly water-soluble drugs.

PMID- 27867111
TI  - Anti-inflammatory activity of Punica granatum L. (Pomegranate) rind extracts
      applied topically to ex vivo skin.
AB  - Coadministered pomegranate rind extract (PRE) and zinc (II) produces a potent
      virucidal activity against Herpes simplex virus (HSV); however, HSV infections
      are also associated with localised inflammation and pain. Here, the objective was
      to determine the anti-inflammatory activity and relative depth penetration of
      PRE, total pomegranate tannins (TPT) and zinc (II) in skin, ex vivo. PRE, TPT and
      ZnSO4 were dosed onto freshly excised ex vivo porcine skin mounted in Franz
      diffusion cells and analysed for COX-2, as a marker for modulation of the
      arachidonic acid inflammation pathway, by Western blotting and
      immunohistochemistry. Tape stripping was carried out to construct relative depth
      profiles. Topical application of PRE to ex vivo skin downregulated expression of
      COX-2, which was significant after just 6h, and maintained for up to 24h. This
      was achieved with intact stratum corneum, proving that punicalagin penetrated
      skin, further supported by the depth profiling data. When PRE and ZnSO4 were
      applied together, statistically equal downregulation of COX-2 was observed when
      compared to the application of PRE alone; no effect followed the application of
      ZnSO4 alone. TPT downregulated COX-2 less than PRE, indicating that tannins alone
      may not be entirely responsible for the anti-inflammatory activity of PRE.
      Punicalagin was found throughout the skin, in particular the lower regions,
      indicating appendageal delivery as a significant route to the viable epidermis.
      Topical application of TPT and PRE had significant anti-inflammatory effects in
      ex vivo skin, confirming that PRE penetrates the skin and modulates COX-2
      regulation in the viable epidermis. Pomegranates have potential as a novel
      approach in ameliorating the inflammation and pain associated with a range of
      skin conditions, including cold sores and herpetic stromal keratitis.

PMID- 27867113
TI  - Glycosylation and antiproliferative activity of hyperglycosylated IFN-alpha2
      potentiate HEK293 cells as biofactories.
AB  - Both CHO and HEK cells are interesting hosts for the production of
      biotherapeutics due to their ability to introduce post-translational
      modifications such as glycosylation. Even though oligosaccharide structures
      attached to proteins are conserved among eukaryotes, many differences have been
      found between therapeutic glycoproteins expressed in hamster and human derived
      cells. In this work, a hyperglycosylated IFN-alpha2b mutein (IFN4N) was produced
      in CHO and HEK cell lines and an extensive characterization of their properties
      was performed. IFN4NCHO exhibited a higher average molecular mass and more acidic
      isoforms compared to IFN4NHEK. In agreement with these results, a 2-times higher
      sialic acid content was found for IFN4NCHO in comparison with the HEK-derived
      protein. This result was in agreement with monosaccharide quantification and
      glycan's analysis using WAX chromatography and HILIC coupled to mass
      spectrometry; all methods supported the existence of highly sialylated and also
      branched structures for IFN4NCHO glycans, in contrast with smaller and truncated
      structures among IFN4NHEK glycans. Unexpectedly, those remarkable differences in
      the glycosylation pattern had not a considerable impact on the clearance rate of
      both molecules in rats. In fact, although IFN4NHEK reached maximum plasma
      concentration 3-times faster than IFN4NCHO, their elimination profile did not
      differ significantly. Also, despite the in vitro antiviral specific biological
      activity of both proteins was the same, IFN4NHEK was more efficient as an
      antiproliferative agent in different tumor-derived cell lines. Accordingly,
      IFN4NHEK showed a higher in vivo antitumor activity in animal models. Our results
      show the importance of an appropriate host selection to set up a bioprocess and
      potentiate the use of HEK293 cells for the production of a new hyperglycosylated
      protein-based pharmaceutical.

PMID- 27867112
TI  - Hydrogel-thickened nanoemulsions based on essential oils for topical delivery of
      psoralen: Permeation and stability studies.
AB  - Nanoemulsions (NE) have attracted much attention due to their as dermal delivery
      systems for lipophilic drugs such as psoralens. However, NE feature low viscosity
      which might be unsuitable for topical application. In this work, we produced
      hydrogel-thickened nanoemulsions (HTN) using chitosan as thickening polymer to
      overcome the low viscosity attributed to NE. The aim of this study is to develop
      and characterize oil-in-water (o/w) HTN based on sweet fennel and clove essential
      oil to transdermal delivery of 8-methoxsalen (8-MOP). NE components (oil,
      surfactant) were selected on the basis of solubility and droplet size and
      processed in a high-pressure homogenizer (HPH). Drug loaded NE and HTN were
      characterized for particle size, stability under storage and centrifugation,
      rheological behavior, transdermal permeation and skin accumulation. Transdermal
      permeation of 8-MOP from HTN was determined by using Franz diffusion cell.
      Transdermal permeation from HTN using clove essential oil showed strong
      dependency chitosan molecular weight. On the other hand, HTN using sweet fennel
      oil showed an unexpected pH-dependent behavior not fully understood at the
      moment. These results need further investigation, nevertheless HTN revealed to be
      interesting and complex dermal delivery systems for poorly soluble drugs.

PMID- 27867116
TI  - Automatic and rapid identification of glycopeptides by nano-UPLC-LTQ-FT-MS and
      proteomic search engine.
AB  - : Here we demonstrate the potential of nano-UPLC-LTQ-FT-MS and the ByonicTM
      proteomic search engine for the separation, detection, and identification of N-
      and O-glycopeptide glycoforms in standard glycoproteins. The use of a BEH C18
      nanoACQUITY column allowed the separation of the glycopeptides present in the
      glycoprotein digest and a baseline-resolution of the glycoforms of the same
      glycopeptide on the basis of the number of sialic acids. Moreover, we evaluated
      several acquisition strategies in order to improve the detection and
      characterization of glycopeptide glycoforms with the maximum number of
      identification percentages. The proposed strategy is simple to set up with the
      technology platforms commonly used in proteomic labs. The method allows the
      straightforward and rapid obtention of a general glycosylated map of a given
      protein, including glycosites and their corresponding glycosylated structures.
      The MS strategy selected in this work, based on a gas phase fractionation
      approach, led to 136 unique peptides from four standard proteins, which
      represented 78% of the total number of peptides identified. Moreover, the method
      does not require an extra glycopeptide enrichment step, thus preventing the bias
      that this step could cause towards certain glycopeptide species. Data are
      available via ProteomeXchange with identifier PXD003578. SIGNIFICANCE: We propose
      a simple and high-throughput glycoproteomics-based methodology that allows the
      separation of glycopeptide glycoforms on the basis of the number of sialic acids,
      and their automatic and rapid identification without prior knowledge of protein
      glycosites or type and structure of the glycans.

PMID- 27867114
TI  - Serine protease inhibitor Kazal-type 2 is expressed in the male reproductive
      tract of carp with a possible role in antimicrobial protection.
AB  - The presence of the low-molecular-mass serine protease inhibitor Kazal-type
      (Spink) is a characteristic feature of vertebrate semen. Its main function is
      control of the serine protease in the acrosome, acrosin. Here we showed for the
      first time that Spink is present in the seminal plasma of carp, which have
      anacrosomal spermatozoa. Using a three-step isolation procedure that consisted in
      gel filtration and RP-HPLC and re-RP-HPLC, we isolated this inhibitor and
      identified it as serine protease inhibitor Kazal-type 2 (Spink2), a reproductive
      derived member of the Spink family. The cDNA sequence of this inhibitor obtained
      from carp testis encoded 77 amino acids, including a 17 amino acids signal
      peptide; this sequence was distinct from fish Kazal-type inhibitors. The mRNA
      expression analysis showed that Spink2 is expressed predominantly in carp testis
      and spermatic duct. Immunohistochemical analysis demonstrated its localization in
      testis in Sertoli, Leydig and germ cells at all developmental stages (with the
      exception of spermatozoa) and in the epithelium of the spermatic duct. Aside from
      strong inhibition of trypsin, this inhibitor acts strongly against subtilisin and
      possesses bacteriostatic activities against Lactobacillus subtilis, Escherichia
      coli and Aeromonas hydrophila. The localization of Spink2 in carp reproductive
      tract suggests an important function in spermatogenesis and in maintenance of the
      microenvironment in which sperm maturation occurs and sperm are stored. Our
      results suggest that Spink2 from carp seminal plasma may play a role in
      antibacterial semen defense, protecting semen against unwanted proteolysis within
      the reproductive tract.

PMID- 27867115
TI  - Central Chemoreceptor Sensitivity Is Not Enhanced in Contemporary Patients With
      Chronic Systolic Heart Failure Receiving Optimal Treatment.
AB  - BACKGROUND: Clinical and prognostic consequences of enhanced central
      chemosensitivity in the contemporary optimally treated patients with chronic
      heart failure (CHF) are unknown. METHODS AND RESULTS: We studied central
      chemosensitivity (defined as hypercapnic ventilatory response [HCVR; L/min/mmHg])
      in 161 CHF patients (mean left ventricular ejection fraction [LVEF] 31 +/- 6%,
      all receiving a combination of angiotensin-converting enzyme
      inhibitor/angiotensin receptor blocker and beta-blocker) and 55 sex- and age
      matched healthy controls. HCVR did not differ between CHF patients and controls
      (median 0.63 vs 0.57 L/min-1/mmHg-1, P = .76). When the CHF patients were divided
      into tertiles according to their HCVR values, there were no significant
      differences in clinical characteristics (except for ischemic etiology, which was
      more frequent in those with the highest HCVR), results of the cardiopulmonary
      exercise testing, and indices of heart rate variability. During the follow-up
      (median 28 months, range 1-48 months, >=15 months in all survivors), 21 patients
      died. HCVR was not related to survival in the Cox proportional hazards analysis.
      CONCLUSIONS: Central chemosensitivity is not enhanced in contemporary, optimally
      treated CHF patients and its assessment does not provide significant clinical or
      prognostic information.

PMID- 27867117
TI  - Extramedullary Cavernous Hemangioma with Intradural and Extradural Growth and
      Clinical Symptoms of Brown-Sequard Syndrome: Case Report and Review of the
      Literature.
AB  - BACKGROUND: Primary spinal tumors are rare. Symptoms depend on the size and
      location of the tumor. CASE DESCRIPTION: A patient presented with a rare clinical
      finding, Brown-Sequard syndrome. The symptoms were caused by an extramedullary
      tumor compressing on the thoracic spinal cord. Pathologic examination showed
      cavernous hemangioma with growth both intradurally and extradurally. CONCLUSIONS:
      This is an extremely rare finding; to our knowledge, only 1 case report has been
      published before in which a spinal cavernous hemangioma had intradural and
      extradural growth. The clinical symptoms of Brown-Sequard syndrome have not been
      described before in the findings of spinal cavernous hemangiomas.

PMID- 27867118
TI  - Giant Parietal Encephalocele with Massive Brain Herniation and Suboccipital
      Encephalocele in a Neonate: An Unusual Form of Double Encephalocele.
AB  - Double encephalocele is extremely rare. We present an unusual form of double
      encephalocele including giant supratentorial and small infratentorial
      encephalocele in a neonate.

PMID- 27867119
TI  - Glioblastoma Secondary to Meningioma: A Case Report and Literature Review.
AB  - BACKGROUND: The pathophysiologies underlying meningioma and glioma are distinct.
      The coexistence of those 2 lesions in the same patient is rare, and at the same
      location, it is even more exceptional. CASE DESCRIPTION: We report a case of a 79
      year-old man initially presenting with a meningioma that was treated by complete
      excision of the lesion. The patient had 2 relapses at the same site, in which
      glioblastoma was confirmed histopathologically. CONCLUSIONS: Glial transformation
      meningiomas remain a contentious issue, with coincidental occurrence being the
      most prevalent explanation. Nevertheless, impairment of the same molecular
      signaling pathways in both tumor types suggests a common origin. Another
      hypothesis is that perilesional parenchymal damage from radiotherapy or surgery
      may lead to glial transformation in the tissues surrounding the original
      meningioma lesion. Further research is needed to determine if the original tumor
      or surgery has an oncogenic effect on the adjacent tissue.

PMID- 27867120
TI  - Transforaminal Resection of Cervical Dumbbell Schwannomas in Patients with
      Additional Tumors.
AB  - BACKGROUND: It is rare for 2 primary tumors to occur simultaneously in a patient.
      Management of cervical dumbbell schwannomas (CDSs) with concurrent tumors (CTs)
      requires a specific neurosurgical strategy. The primary objective of this study
      is to investigate surgical strategies for CDSs with CTs while preserving as much
      of the mechanically relevant bone structures as possible. METHODS: Twelve
      patients with concurrent CTs and CDSs were identified from 3 medical centers.
      Surgical strategies for CDSs were based on accurate preoperative images and
      subsequent treatment considerations for CTs. All patients received surgical
      treatment for CDSs and CTs. Clinical features, surgical considerations for a
      transforaminal approach (TA), and ultimate outcome were studied retrospectively.
      RESULTS: Gross total resection of CDSs was achieved with endoscopic and
      microscopic assistance in 9 cases, and subtotal resection was achieved in 3 cases
      after the head and neck surgeons exposed and removed the extraforaminal anatomy.
      One patient required an additional hemilaminectomy for the resection of the
      intraspinal segment. After wound healing, patients were transferred to the
      appropriate surgical department for surgery on CTs with cervical spine
      stabilization after a transforaminal approach. CONCLUSIONS: In most patients, the
      stability of the cervical spine can be preserved with low invasive microsurgical
      or endoscopic transforaminal resection. CTs could be surgically treated
      sequentially after microscopic- and endoscopic-assisted resection of CDSs.

PMID- 27867121
TI  - Effect of Direct Stimulation of the Cochleovestibular Nerve on Tinnitus: A Long
      Term Follow-Up Study.
AB  - OBJECTIVE: Tinnitus is a common entity that may lead to severe impairment in
      quality of life. An adequate treatment modality for severe tinnitus is currently
      lacking. Neurostimulation of the auditory tract may serve as a promising adjunct
      in tinnitus treatment. The aim is to investigate the effect of direct stimulation
      on the cochleovestibular nerve for intractable tinnitus. METHODS: This study was
      conducted at the University Medical Center Groningen, The Netherlands. We studied
      10 patients with severe, unilateral, intractable tinnitus, who were implanted
      with a cuff electrode around the cochleovestibular nerve between 2001 and 2013.
      All patients had preoperative ipsilateral hearing loss. Tinnitus Handicap
      Inventory (THI) scores and audiometric values were collected. Treatment success
      was determined based on the self-assessment of satisfactory usage by each
      patient. RESULTS: The mean preoperative tinnitus duration was 8.0 +/- 5.9 years.
      The preoperative THI score was 71 +/- 18 points. During mean follow-up of 49
      months, the mean THI reduction was 24 +/- 26 points (P = 0.02). Treatment was
      regarded successful in 6 patients (60%). In these patients, tinnitus did not
      disappear, but transformed into a more bearable sound. In 4 patients, transient
      complications occurred, and 1 patient experienced permanent vertigo
      postoperatively. Furthermore, hearing deterioration was a result of implantation
      in 86% of the patients. CONCLUSIONS: Direct neurostimulation resulted in
      treatment success in a small majority of the patients, with a significant
      decrease in THI score. However, because of a high risk of additional hearing
      damage, this technique seems not viable for patients with moderate hearing loss.

PMID- 27867122
TI  - Resolution of Trigeminal Neuralgia After Transvenous Embolization of a Cavernous
      Sinus Dural Arteriovenous Fistula.
AB  - BACKGROUND: Trigeminal neuralgia (TN) resulting from a dural arteriovenous
      fistula (DAVF) are rare. A case of cavernous sinus dural arteriovenous fistula
      (CSDAVF) in a patient with TN that resolved immediately after transvenous
      embolization (TVE) is described. CASE DESCRIPTION: A 75-year-old woman presented
      with continuous facial pain. On time-of-flight magnetic resonance angiography
      (MRA), a CSDAVF was suspected, and digital subtraction angiography (DSA) showed a
      CSDAVF. The TN completely resolved immediately after TVE, with no recurrence.
      Follow-up MRA showed complete obliteration of the fistula 13 months after TVE.
      CONCLUSIONS: The pulsatile flow at the posteromedial part of the cavernous sinus
      might have compressed the upper aspect of the Gasserian ganglion, causing TN.
      Disappearance of pulsatile flow after TVE might result in complete resolution of
      TN.

PMID- 27867123
TI  - Significance of the Extent of Resection in Modern Neurosurgical Practice of World
      Health Organization Grade I Meningiomas.
AB  - OBJECTIVE: Since the prognostic importance of radical resection was introduced in
      1957, the neurosurgery practice has undergone several technologic advancements.
      The aim of this study was to evaluate whether the prognostic value of the extent
      of resection is still relevant in modern neurosurgical practice. METHODS: Over a
      10-year period, all patients with histologic-confirmed World Health Organization
      grade I meningiomas and who underwent meningioma surgery were retrospectively
      analyzed. Survival analyses were performed using Kaplan-Meier analysis and
      univariate and multivariate Cox proportional-hazards regression analyses.
      RESULTS: There were 113 patients included in this study. A better Simpson grade
      was associated with recurrence-free survival (RFS) 5, 10, and 15 years after
      surgery (P < 0.001). Comparing Simpson grade I with Simpson grades III and IV,
      13.1 and 36.6 times higher hazard ratios were revealed with respect to RFS,
      respectively. A 7.5 times higher hazard ratio was revealed when comparing Simpson
      grades II and IV. Additional survival analyses were performed within specific
      locations and groups with low and high mitotic indices, demonstrating that the
      extent of resection can add additional information about RFS. CONCLUSIONS:
      Simpson grade remains a highly significant predictor of RFS in meningioma
      resected patients in modern neurosurgical practice. Extent of resection should
      therefore be emphasized when predicting prognosis and considering postoperative
      treatment and frequency of radiologic follow-up after surgery.

PMID- 27867125
TI  - Choosing a Prescription Isodose in Stereotactic Radiosurgery for Brain
      Metastases: Implications for Local Control.
AB  - OBJECTIVE: Stereotactic radiosurgery (SRS) achieves excellent local control (LC)
      with limited toxicity for most brain metastases. SRS dose prescription variables
      influence LC; therefore, we evaluated the impact of prescription isodose line
      (IDL) on LC after SRS. METHODS: A retrospective analysis of patients with brain
      metastases treated on a Gamma Knife platform from 2004 to 2014 was conducted.
      Clinical, toxicity, radiographic, and dosimetric data were collected. Cox
      proportional hazards regression was used to determine progression-free survival
      (PFS) and competing risks analysis was used to determine predictive factors for
      LC. RESULTS: A total of 134 patients with 374 brain metastases were identified
      with a median survival of 8.7 months (range, 0.2-64.8). The median tumor maximum
      dimension was 8 mm (range, 2-62 mm), median margin dose was 20 Gy (range, 5-24
      Gy), and 12-month LC rate was 88.7%. On multivariate analysis, PFS improved with
      increasing IDL (P = 0.003) and decreased with non-non-small-cell lung cancer
      histology (P = 0.001). Margin dose, tumor size, conformality, and previous whole
      brain irradiation failed to independently affect PFS. When adjusting for death as
      a competing risk, the cumulative likelihood of LC improved with higher IDL (P =
      0.04). The rate of SRS-induced radiographic and clinical toxicity was low (16.6%
      and 1.5%, respectively), and neither was affected by IDL. CONCLUSIONS: Our
      results confirm that SRS for brain metastases results in favorable LC,
      particularly for patients with smaller tumors. We noted that dose delivery to a
      higher prescription IDL is associated with small but measurable improvements in
      LC. This finding could be related to higher dose just beyond the radiographically
      apparent tumor.

PMID- 27867124
TI  - Ventral Dural Injury After Oblique Lumbar Interbody Fusion.
AB  - BACKGROUND: Oblique lumbar interbody fusion (OLIF) through the oblique corridor
      between the aorta and anterior border of psoas muscle is favored among spinal
      surgeons who employ minimally invasive techniques. We report a case of ventral
      dural tear after OLIF that was associated with the inaccurate trajectory
      direction of endplate preparation. This is the first report to our knowledge of
      ventral dural tear associated with OLIF. CASE DESCRIPTION: A 72-year-old woman
      presented with right leg pain and numbness. X-rays showed degenerative
      spondylolisthesis and loss of disc height at L4-L5 and L5-S1 levels. Magnetic
      resonance imaging revealed right-sided paracentral disc herniation at the L3-L4
      level and foraminal disc herniation at L4-L5. The initial surgical plan was OLIF
      of L3-L4 and L4-L5 after percutaneous screw fixation without laminectomy. With
      the patient in the lateral position, discectomy and endplate preparation were
      done successfully at the L3-L4 level, and the same procedure was done at the L4
      L5 level for OLIF. A sharp Cobbs elevator for endplate preparation triggered a
      ventral dural defect at the L4-L5 level. We changed the patient's position to
      attempt dural repair. The ventral dural defect could not be repaired because it
      was too large. After the herniated rootlets were repositioned, TachoComb was
      patched over the defect site. Postoperatively, the patient has no definite
      neurologic deficits. CONCLUSIONS: When a surgeon performs OLIF, ventral dural
      injury should be avoided during the procedure of endplate preparation and
      contralateral annular release.

PMID- 27867126
TI  - Coiling Is Not Superior to Clipping in Patients with High-Grade Aneurysmal
      Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Outcomes of coiling embolization versus clipping for patients with
      high-grade aneurysmal subarachnoid hemorrhage (aSAH) have not been previously
      compared. We reviewed current evidence regarding the safety and efficacy of
      clipping versus coiling for high-grade aSAH. METHODS: We conducted a meta
      analysis of studies that compared clipping with coiling in patients with high
      grade aSAH published from January 1999 to February 2016 in Medline, Embase, and
      Cochrane databases based on PRISMA inclusion and exclusion criteria. Binary
      outcome comparisons between clipping and coiling were described using odds ratios
      (ORs). RESULTS: Three randomized controlled trials (RCTs) and 16 observational
      studies were included. There was no statistical difference in good outcome rates
      between the clipping and coiling groups (OR, 1.44; 95% confidence interval [CI],
      0.97-2.13). Subgroup analysis showed no significant difference between the 2
      treatments in non-RCTs (OR, 1.49; 95% CI, 0.95-2.36) and RCTs (OR, 1.15; 95% CI,
      0.59-2.25). Coiling was associated with higher mortality (OR, 0.55; 95% CI, 0.41
      0.75). Lower mortality was associated with clipping in non-RCTs (OR, 0.54; 95%
      CI, 0.40-0.74), but there was no difference in the RCTs (OR, 0.79; 95% CI, 0.19
      3.39). Coiling was not associated with lower rates of complications including
      rebleeding (OR, 0.62; 95% CI, 0.30-1.29), ischemic infarct (OR, 0.89; 95% CI,
      0.53-1.49), symptomatic vasospasm (OR, 0.76; 95% CI, 0.45-1.29), or shunt
      dependent hydrocephalus (OR, 1.33; 95% CI, 0.52-3.40). CONCLUSION: The outcome
      with coiling is not superior to clipping in patients with high-grade aSAH;
      moreover, coiling has a greater risk of mortality.

PMID- 27867127
TI  - Salvage Revision Surgery After Inappropriate Approach for Primary Spine Tumors:
      Long Term Follow-Up in 56 Cases.
AB  - BACKGROUND: The mainstay treatment of primary malignant bone tumors is wide
      surgery in the spine. Unfortunately, most cases undergo the first approach in a
      nonspecialized center; this often means adopting an inappropriate approach with
      contamination, which consistently decreases the effectiveness of a second
      surgery. The aim of the present paper is to evaluate recurrence and survival
      rates after en-bloc resection. METHODS: All patients underwent wide resection by
      the senior author from January 1997 to December 2013 after the first
      inappropriate approach was reviewed. Fifty-six patients were included in the
      present evaluation. Epidemiologic and clinical characteristics, surgeries, early
      and late complications, and survival rate were reported. RESULTS: The margin
      obtained was wide, marginal, and intralesional in 9, 28, and 19 cases,
      respectively. The complication rates were 55.4% and 44.6% for early and late
      complications, respectively. Most (73.2%) of the patients had complications. The
      survival rate is 82.1% at 1 year and then decreases 10% each year until 42.1% at
      5 years from surgeries. No statistically significant correlation was found
      between margin and local recurrence and survival. CONCLUSION: In our series, the
      first inappropriate approach had already compromised patient prognosis, so in
      case of suspicious primary spine tumor, the patient had to be referred to a
      specialized center. The margin obtained during salvage surgery does not appear to
      influence recurrence and survival, probably because it is already compromised by
      the first surgery. More prospective studies are necessary to confirm our data and
      verify the impact of the margin obtained during salvage surgery on patients'
      survival.

PMID- 27867128
TI  - Evaluation of Meropenem Penetration into Cerebrospinal Fluid in Patients with
      Meningitis After Neurosurgery.
AB  - OBJECTIVE: Meropenem is important for management of postneurosurgical meningitis,
      but the data about its penetration into cerebrospinal fluid (CSF) are inadequate.
      This prospective, open-label study investigated the pharmacokinetic profile of
      meropenem in patients with postneurosurgical meningitis, especially its CSF
      penetration. METHODS: A total of 82 patients with postneurosurgical meningitis
      were included to receive meropenem intravenously according to a regimen of 2 g
      every 8 hours, 1 g every 8 hours, or 1 g every 6 hours. After infusion of 4
      doses, blood and CSF samples were collected simultaneously at predefined time
      points. The high-performance liquid chromatography ultraviolet method was used to
      determine the concentration of meropenem. RESULTS: The peak meropenem
      concentration in blood and CSF was 43.2 +/- 5.3 and 2.4 +/- 0.3 mg/L in the group
      who received 2 g every 8 hours; 28.9 +/- 2.7 and 1.2 +/- 0.2 mg/L in the group
      who received 1g every 8 hours; and31.5 +/- 3.4 and 1.6 +/- 0.2 mg/L in the group
      who received 1g every 6 hours. The maximal percent penetration into CSF was 17.6%
      +/- 7.3%, 14.3% +/- 1.7%, and 30.9% +/- 24.2%, respectively. CONCLUSIONS: Dosing
      regimens of meropenem 1 g every 6 hours and 2 g every 8 hours provided higher CSF
      penetration than 1 g every 8 hours. A higher dose and shorter dosing interval of
      meropenem may be more useful for clearance of pathogens.

PMID- 27867129
TI  - Interventions for Lumbar Synovial Facet Joint Cysts: A Comparison of
      Percutaneous, Surgical Decompression and Fusion Approaches.
AB  - OBJECTIVE: Facet joint cysts (FJCs) of the lumbar spine are an increasingly
      reported cause of radiculopathy, lower back pain, and neurologic deficits.
      Currently, there is a lack of conclusive evidence outlining when a particular
      treatment should be undertaken and what patient indications suit a particular
      approach. The present systematic review and meta-analysis aims to evaluate the
      efficacy of percutaneous treatment and surgical decompression with or without
      fusion. METHODS: A systematic literature search of scientific databases from
      their inception to February 2016 was performed by 2 reviewers. Studies pertaining
      to percutaneous procedures, decompressive surgeries, or decompressive surgeries
      with fusion for the treatment of lumbar facet joint cysts were identified. Data
      for resolution of symptoms, repeat procedures, and subsequent fusion were
      extracted and analyzed. RESULTS: Fifty studies comprising 870 patients with
      lumbar FJCs were identified for inclusion. Decompressive procedures were
      performed in 62.8% of patients, whereas 36.1% were treated by percutaneous
      aspiration or rupture, and only 1.1% were treated by decompression with fusion.
      Pooled analysis showed the rate of cyst resolution to be 90% for decompressive
      procedures with or without fusion and 58% for percutaneous procedures. Repeat
      procedures were required in 29% of percutaneous procedures, but less than 1% for
      all decompression operations. CONCLUSIONS: Evaluation of the literature shows
      surgical intervention to be advantageous over percutaneous procedures for the
      treatment of lumbar FJCs. There is no evidence suggesting when fusion should be
      undertaken because of the limited data available.

PMID- 27867130
TI  - Bilateral Ossified Chronic Subdural Hematoma Presenting as Diabetes Insipidus
      Case Report and Literature Review.
AB  - Calcified chronic subdural hematomas are an occurrence rarely seen in
      neurosurgical clinical practice. And when they occur bilaterally, the radiologic
      image they present is fascinating, as is the clinical presentation, but their
      management may be challenging. They have been reported to present with a
      multitude of neurologic deficits but never with diabetes insipidus, which is
      described here. Due to the rarity of this pathology, the management protocol is
      not well defined, though there have been quite a few papers on this condition.
      This review article gathers information published over the years on this rare
      entity to suggest a treatment protocol.

PMID- 27867132
TI  - Learning curve for real-time ultrasound-guided percutaneous tracheostomy.
AB  - OBJECTIVES: The objective of this study was to demonstrate and quantify the
      ultrasound-guided percutaneous tracheostomy (UPDT) learning curve in a single
      team since the first UPDT. STUDY DESIGN AND PATIENTS: This was a cohort of all
      consecutive patients undergoing UPDT in the Amiens teaching hospital surgical
      intensive care unit between 2010 and 2014. METHODS: The learning process was
      evaluated according to three aspects: duration of the various steps involved in
      UPDT, incidence of consecutive complications, and procedure difficulty. RESULTS:
      During the study period, 85 consecutive patients underwent UPDT with no deaths.
      The mean total procedure time was 22 (10) minutes (range: 7 to 60). Analysis of
      mean cumulative UPDT procedure times showed that total UPDT time decreased to a
      stable duration of 25minutes after 54 procedures. Complications were observed in
      24 (28%) of the 85 patients. The overall complication rate decreased to below a
      stable percentage of 30% after 70 procedures. The minor complication rate
      decreased below 25% after 64 procedures. The moderate complication rate decreased
      to below a stable percentage of 10% after 10 procedures. The major complication
      rate decreased to below a stable percentage of 5% after 20 procedures. Most
      complications were observed in the first 50 patients (25 [50%] versus 6 [13%],
      P<0.05). CONCLUSIONS: Our study demonstrated that UPDT is associated with a
      fairly long learning curve. At least 50 procedures are necessary to perform UPDT
      with an acceptable complication rate and procedure time.

PMID- 27867131
TI  - Neuronavigation Based on Track Density Image Extracted from Deterministic High
      Definition Fiber Tractography.
AB  - BACKGROUND: Diffusion tensor imaging-based navigation is unable to resolve
      crossing fibers or to determine with accuracy the fanning, origin, and
      termination of fibers. It is important to improve the accuracy of localizing
      white matter fibers for improved surgical approaches. We propose a solution to
      this problem using navigation based on track density imaging extracted from high
      definition fiber tractography (HDFT). CASE DESCRIPTION: A 28-year-old
      asymptomatic female patient with a left-lateral ventricle meningioma was enrolled
      in the present study. Language and visual tests, magnetic resonance imaging
      findings, both preoperative and postoperative HDFT, and the intraoperative
      navigation and surgery process are presented. Track density images were extracted
      from tracts derived using full q-space (514 directions) diffusion spectrum
      imaging (DSI) and integrated into a neuronavigation system. Navigation accuracy
      was verified via intraoperative records and postoperative DSI tractography, as
      well as a functional examination. DSI successfully represented the shape and
      range of the Meyer loop and arcuate fasciculus. Extracted track density images
      from the DSI were successfully integrated into the navigation system. The
      relationship between the operation channel and surrounding tracts was consistent
      with the postoperative findings, and the patient was functionally intact after
      the surgery. CONCLUSIONS: DSI-based TDI navigation allows for the visualization
      of anatomic features such as fanning and angling and helps to identify the range
      of a given tract. Moreover, our results show that our HDFT navigation method is a
      promising technique that preserves neural function.

PMID- 27867133
TI  - Fiber optic bronchoscopy and remifentanil target-controlled infusion in
      critically ill patients with acute hypoxaemic respiratory failure: A descriptive
      study.
AB  - INTRODUCTION: Sedation optimizes patient comfort and ease of execution during
      fiber optic bronchoscopy (FOB). Our objective was to describe the safety and
      efficacy of remifentanil-TCI during FOB in non-intubated, hypoxaemic, thoracic
      surgery ICU patients. METHODS: Consecutive spontaneously breathing adults
      requiring FOB after thoracic surgery were included if they had hypoxaemia
      (PaO2/FiO2<300mmHg or need for non-invasive ventilation [NIV]) and prior FOB
      failure under topical anaesthesia. The remifentanil initial target was chosen at
      1ng/mL brain effect-site concentration (Cet), then titrated to 0.5ng/mL Cet
      increments according to patient comfort and coughing. Outcomes were patient
      reported pain and discomfort (Visual Analogue Scale scores), ventilatory support
      intensification within 24hours after bronchoscopy, and ease of FOB execution.
      RESULTS: Thirty-nine patients were included; all had a successful FOB. Their
      median PO2/FiO2 before starting FOB was 187+/-84mmHg and 24 patients received
      NIV. Median [interquartile range] pain scores were not different before and after
      FOB (1.0 [0.0-3.0] and 0.0 [0.0-2.0], respectively). Discomfort was reported as
      absent or minimal by 27 patients (69%; 95% confidence interval [95% CI], 54-81%)
      and as bothersome but tolerable by 12 patients (31%; 95% CI, 19-46%). Mean FiO2
      returned to baseline within 2hours after FOB in 30 patients; the remaining 9
      patients (23%; 95% CI, 13-38%) received ventilatory support intensification. Ease
      of execution was good or very good in 34 patients (87%; 95% CI, 73-94%),
      acceptable in 4 patients, and poor in 1 patient (persistent cough). CONCLUSION:
      Sedation with remifentanil-TCI during FOB with prior failure under topical
      anaesthesia alone was effective and acceptably safe in non-intubated hypoxaemic
      thoracic surgery patients.

PMID- 27867134
TI  - Residual anxiety after high fidelity simulation in anaesthesiology: An
      observational, prospective, pilot study.
AB  - BACKGROUND: High fidelity simulation (HFS) in anaesthesiology intentionally
      provides stress on students, but anxiety may be detrimental if it goes on through
      debriefing. The primary goal of this study was to estimate the proportion of
      students with significant anxiety remaining after debriefing (residual anxiety
      [RA]). Secondary goals were to evaluate the instructors' ability to estimate
      students' RA and to identify potential risk factors for high RA. SUBJECTS AND
      METHODS: Following IRB approval and informed consent, data from a cohort of
      subjects were prospectively collected by an independent expert. State-anxiety
      after debriefing (RA) was prospectively measured using the State-Trait Anxiety
      Inventory (a score varying from 20 to 80/80). RA was considered significant
      when>=36/80. Instructors simultaneously estimated the levels of subjects' RA via
      a visual analogue scale. Data about subjects, stress during scenarios (including
      continuous heart rate monitoring), and debriefings (including DASH(c) quality
      scores) were also collected. RESULTS: Seventy study subjects (30 residents, 26
      nurses and 14 anaesthetists) were enrolled during 52 HFS sessions. As concerns
      the primary endpoint, RA was>=36/80 in 15 subjects (21%; 95% CI: 13-32). The
      median RA was 30/80 [25-35]. For secondary endpoints, the instructors'
      estimations poorly correlated with measurements: rho=0.36 (P<0.01); limits of
      agreement: -16 and 22. Subjects with RA>=36/80 had significantly higher trait
      anxiety (P<0.01). An easy scenario (P=0.04) and low quality debriefing (P=0.04)
      were associated with higher RAs. CONCLUSION: Most students experienced low
      anxiety after debriefing. Instructors seem to be unable to reliably estimate
      students' RA. Students with an anxious personality are more likely to be anxious
      after debriefing.

PMID- 27867135
TI  - Comparison of capillary and arterial lactate levels in patients with shock.
AB  - OBJECTIVE: Several guidelines recommend point-of-care lactate measurements for
      therapeutic decision-making in patients with shock. The aim of the study was to
      validate capillary lactate measurements with a bedside micromethod in patients
      with shock. STUDY DESIGN: Prospective observational study. PATIENTS AND
      MEASUREMENTS: Capillary lactate levels measured by a micromethod (CAPI) and
      arterial lactate levels measured by a standard laboratory method (ARTs) were
      simultaneously and repeatedly assayed in consecutive ICU patients with shock. The
      validity and clinical acceptability of the CAPI method was assessed from its
      reproducibility, the arterio-capillary lactate difference (ACLD) and conventional
      diagnostic indicators. MAIN RESULTS: Lactate measurements were available for 139
      time-points in 37 patients. CAPI values correlated well with ARTs values
      (intraclass coefficient correlation: r2=0.92, P<0.001). CAPI had a sensitivity of
      98%, a specificity of 36%, an accuracy of 88% and a positive predictive value of
      89% to detect lactate values>=2mmol/L (P<0.0001). The mean bias between the two
      methods (ACLD: 0.56+/-2.21mmol/L) was mainly due to higher lactate concentration
      in capillary blood. CONCLUSION: CAPI was correctly correlated to ARTs. The bias
      between the two methods is probably acceptable for triage purpose. Patients with
      elevated capillary lactate or in shock should be monitored with atrial-based
      lactate.

PMID- 27867136
TI  - Pediatric orthopedic surgery in humanitarian aid.
AB  - Pediatric orthopedic surgery in humanitarian aid is conducted mainly in
      cooperation with emerging countries. Each mission is different, and depends on
      numerous parameters such as the country, the frequency of such missions, the
      pathologies encountered, the local structure and team, and the non-governmental
      organization (NGO) involved. Pathologies vary in etiology (tuberculosis,
      poliomyelitis) and severity. Each mission requires the presence of an experienced
      surgeon. Working conditions are often rudimentary. Surgical indications should be
      restricted to procedures that are going to be effective, with minimal
      postoperative complications, without any surgical "acrobatics". Teaching should
      be in association with the local university, and adapted to local needs. Mission
      objectives need to be realistic. Surgical indications should be adapted to local
      conditions, and the surgeon needs to be able to say "no" to procedures involving
      undue risk. The surgeon on mission should cooperate with local teams and be able
      to adapt to unusual situations. Assessment of results is essential to improving
      efficacy and evaluating the success of the mission.

PMID- 27867137
TI  - Minimally invasive internal fixation of distal femur fractures.
AB  - Fractures of the distal femur remain a daunting challenge. Since 1970, operative
      treatment has been recommended. Unfortunately, it is fraught with complications,
      and techniques have been developed to limit incidence of non-union, infection and
      stiffness. A soft-tissue friendly approach is the key point, with minimally
      invasive surgery as the ultimate goal: its biological and anatomical advantages
      have been demonstrated, but clinical studies have been less convincing, being
      based on historical series. At present, retrograde nailing and minimally invasive
      percutaneous plate osteosynthesis (ideally by locking plate) are the two main
      techniques. Unfortunately, reports tend to compare implants rather than operative
      techniques, hindering solid conclusions. Lastly, the delineation of "distal femur
      fracture" is quite variable, sometimes situated well above the AO epiphyseal
      square. Meta-analyses find almost no difference between the two implants in
      minimally invasive procedures. The main advantage of the plate is its
      versatility, whereas nailing can be impossible in case of certain hip or knee
      prostheses, compound articular fracture or medullary canal obstruction by
      fixation material (nail, stem, screw, etc.). The role of arthroscopy is limited.
      Only a few case reports describe its use in reduction of epiphyseal fracture. In
      the last analysis, the surgeon's experience is more relevant to outcome than any
      particular implant.

PMID- 27867138
TI  - Are the AMPLATZER Duct Occluder II Additional Sizes devices dedicated only for
      smaller children?
AB  - AIMS: The aim of this study was to present our experience with the AMPLATZER Duct
      Occluder II Additional Sizes (ADOIIAS) for the closure of different types of
      patent ductus arteriosus (PDA) in patients of various age groups. METHODS AND
      RESULTS: A group of 103 patients, in whom the PDA (diameter below 3.5 mm) was
      closed using the ADOIIAS, was analysed. The median age of treated patients was
      3.0 years (from 0.1 to 24 years), and 55 patients (53.4%) were older than three
      years. Ductal anatomy defined by angiography showed type A in 42 patients
      (40.8%), type C in six patients (5.8%), type D in 21 patients (20.5%), and type E
      in 34 patients (33.0%). In two cases, embolisation of the device occurred shortly
      after implantation. Both occluders were retrieved percutaneously. One death
      occurred in a neonate four days after ADOIIAS implantation (not related to the
      procedure: multi-organ failure). Total occlusion of PDA was confirmed in all
      patients the day after the procedure. No protrusion of the device into the aorta
      or pulmonary artery was observed in any patient during follow-up. CONCLUSIONS:
      The use of the ADOIIAS is a good therapeutic option for the treatment of selected
      PDA. The implant may be successfully substituted for coil implantation in all age
      groups.

PMID- 27867141
TI  - Sex differences in plaque characteristics by intravascular imaging in patients
      with coronary artery disease.
AB  - AIMS: We aimed to study sex differences in coronary plaque burden and plaque
      composition in patients with coronary artery disease (CAD). METHODS AND RESULTS:
      Virtual histology intravascular ultrasound (VH-IVUS) and near-infrared
      spectroscopy (NIRS) imaging of a non-culprit coronary artery was performed in 178
      (23.5%) women and 581 (76.5%) men who underwent invasive management of stable
      angina pectoris (SAP) or acute coronary syndrome (ACS). Women were older and had
      a worse cardiovascular risk profile than men, but less extended angiographic
      coronary disease. Irrespective of the presenting diagnosis, women had lower VH
      IVUS-derived plaque burden than men (38.1% vs. 40.5% in SAP, and 35.9% vs. 38.8%
      in ACS). Standardised (mean 211 vs. 263 mm3 in SAP, and 199 vs. 245 mm3 in ACS)
      total plaque volume was lower in women. Volumes of fibrous tissue, fibro-fatty
      tissue, necrotic core and dense calcium were also lower in women. NIRS-derived
      lipid core burden index (LCBI) was lower in women, in particular in SAP (mean
      LCBI in the worst 4 mm 220 vs. 240). The observed differences remained
      significant after adjustment for clinical characteristics. CONCLUSIONS: Women had
      more favourable plaque characteristics than men, despite their worse risk
      profile. Long-term follow-up studies are required to evaluate the clinical
      consequences.

PMID- 27867140
TI  - Impact of calcified bifurcation lesions in patients undergoing percutaneous
      coronary intervention using drug-eluting stents: results from the COronary
      BIfurcation Stent (COBIS) II registry.
AB  - AIMS: Few data regarding clinical outcomes according to severity of calcification
      in patients with coronary bifurcation target lesions are available. We therefore
      aimed to evaluate the clinical outcomes according to severity of calcification in
      patients with coronary bifurcation target lesions after percutaneous coronary
      intervention (PCI) with drug-eluting stents (DES) using a large-scale multicentre
      Korean registry. METHODS AND RESULTS: This prospective, multicentre,
      observational registry enrolled 2,897 patients undergoing PCI with DES for
      coronary bifurcation lesions. We compared target lesion failure (TLF), defined as
      a composite of cardiac death, non-fatal myocardial infarction (MI), and target
      lesion revascularisation (TLR), according to severity of calcification in
      coronary bifurcation target lesions, assessed by an angiographic core laboratory
      using quantitative coronary angiography. Moderate or severe calcification of
      target bifurcation lesions was observed in 608 (20.9%) patients. During a median
      follow-up period of 36 months, moderate or severe calcification increased the
      adjusted risks of TLF (hazard ratio [HR] 1.31, 95% confidence interval [CI]: 1.03
      1.68, p=0.031), TLR (HR 1.36, 95% CI: 1.04-1.79, p=0.027), and revascularisation
      (HR 1.39, 95% CI: 1.09-1.78, p=0.009). However, it was not associated with an
      increased risk of cardiac death, MI, or stent thrombosis. CONCLUSIONS: Moderate
      or severe calcification of coronary bifurcation lesions is not uncommon and is
      associated with unfavourable long-term clinical outcomes, driven mainly by an
      increased frequency of repeat revascularisation.

PMID- 27867142
TI  - Impact of plaque type and side branch geometry on side branch compromise after
      provisional stent implantation: a simulation study.
AB  - AIMS: Mechanisms of lumen compromise after provisional side branch (SB) stenting
      are poorly understood. In this study we aimed to investigate the impact of
      bifurcation angle, plaque composition, and procedural strategy on SB compromise.
      METHODS AND RESULTS: Computer simulations of stent implantation were performed in
      Medina (1,1,1) bifurcation models. Provisional SB stenting was replicated
      including post-dilation after main branch stenting. Two bifurcation angles (45
      degrees , 70 degrees ) and four plaque types (fully lipid, fully fibrous, lipid
      with half and fully calcified ring distal to the carina) were tested. Two post
      dilation balloons of different lengths (15 mm and 9 mm) were also investigated.
      Provisional stenting caused an ovalisation of the SB ostium (i.e., increase of
      ellipticity from 0.27 to 0.58+/-0.21, p<0.05) that might appear as a significant
      stenosis on two-dimensional angiography, although SB ostium area was preserved (
      3.3+/-10.3%) in the absence of calcifications. However, in the presence of
      calcifications, SB lumen volume compromise was evident (-0.89+/-0.15 mm3). Plaque
      type had a higher impact than bifurcation angle on SB ostium shape. A shorter
      balloon (9 mm) for proximal optimisation reduced SB lumen volume compromise from 
      1.11 mm3 to -0.72 mm3. CONCLUSIONS: Simulations showed ovalisation of the SB
      ostium, generally without significant lumen compromise. Provisional stenting in
      the presence of calcifications resulted in a more severe outcome for the SB
      ostium.

PMID- 27867143
TI  - Survival after percutaneous coronary intervention for chronic total occlusion in
      elderly patients.
AB  - AIMS: Few data are available on outcomes of percutaneous coronary intervention
      (PCI) for coronary chronic total occlusions (CTO) in very elderly patients in the
      drug-eluting stent (DES) era. We aimed to investigate long-term survival in a
      single-centre cohort of elderly patients following CTO PCI using DES. METHODS AND
      RESULTS: A total of 2,002 consecutive patients who underwent PCI of a CTO at our
      centre between January 2005 and December 2013 were followed for a median of 2.6
      years (interquartile range 1.1-3.1 years). Four hundred and nine (409) patients
      were older than 75 years. The absolute reduction in all-cause mortality by
      successful CTO PCI was numerically greater in elderly patients as compared to
      younger patients (22.1% vs. 7.2% at three years). In multivariate models,
      successful CTO PCI was significantly associated with improved survival in both
      elderly (adjusted hazard ratio [HR] 0.58, 95% confidence interval [CI]: 0.39 to
      0.87; p=0.009) and younger patients (adjusted HR 0.59, 95% CI: 0.40 to 0.86;
      p=0.006). CONCLUSIONS: In the DES era, elderly patients (>=75 years) derive a
      similar survival benefit from successful CTO PCI to younger patients. These
      findings suggest that CTO PCI, when indicated, should not be withheld from the
      elderly.

PMID- 27867144
TI  - Palliative care in Pakistan.
AB  - Pakistan is a developing country of South East Asia, with all the incumbent
      difficulties currently being faced by the region. Insufficient public healthcare
      facilities, poorly regulated private health sector, low budgetary allocation for
      health, improper priority setting while allocating limited resources, have
      resulted essentially in an absence of palliative care from the healthcare scene.
      Almost 90% of healthcare expenditure is out of the patient's pocket with more
      than 45% of population living below the poverty line. All these factors have a
      collective potential to translate into an end-of-life care disaster as a large
      percentage of population is suffering from chronic debilitating/terminal
      diseases. So far, such a disaster has not materialised, the reason being a family
      based culture emphasising the care of the sick and old at home, supported by
      religious teachings. This culture is not limited to Pakistan but subsists in the
      entire sub-continent, where looking after the sick/elderly at home is considered
      to be the duty of the younger generation. With effects of globalisation, more and
      more older people are living alone and an increasing need for palliative care is
      being realised. However, there does not seem to be any plan on the part of the
      public or private sectors to initiate palliative care services. This paper seeks
      to trace the social and cultural perspectives in Pakistan with regards to
      accessing palliative care in the context of healthcare facilities available.

PMID- 27867145
TI  - Human papillomavirus vaccines, complex regional pain syndrome, postural
      orthostatic tachycardia syndrome, and autonomic dysfunction - a review of the
      regulatory evidence from the European Medicines Agency.
AB  - Recent concerns about a possible association between exposure of young women to
      human papillomavirus (HPV) vaccines and two "dysautonomic syndromes" (a
      collection of signs and symptoms thought to be caused by autoimmunity) - complex
      regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome
      (POTS) - led the European Medicines Agency (EMA) to review existing evidence. The
      review was announced by the EMA on July 13, 2015, and was completed on November
      4, 2015.

PMID- 27867146
TI  - Genomics: disclose the influence of human specific genetic variation on the
      evolution and development of cerebral cortex.
AB  - Cerebral cortex, whose complexity of structure and function has derived from
      human specific genetic variation, is the most advanced nerve center of human,
      controlling the cognitive ability which distinguishes human from any other
      creatures. Using genomics technology, molecular mechanisms of cerebral cortex
      development and evolution have been disclosed. In this review, we summarize how
      genomics technologies are used in exploring the influence of human specific
      genetic variation on cerebral cortex development and evolution, including the
      genomics methods to study the gene expression differences among the cerebral
      cortex of human beings, chimpanzee and other mammals; as well as the role of the
      significant non-coding regulatory sequences-human accelerated regions (HARs) in
      the process of brain development. We also discuss the future research trends on
      the human specific genetic variation in the field of neurobiology.

PMID- 27867147
TI  - Evolution of KRAB-containing zinc finger proteins and their roles in species
      evolution.
AB  - The C2H2 zinc finger protein family, one of the largest families of transcription
      factor/transcriptional regulator in mammal, arose from a small ancestral group of
      eukaryotic zinc finger transcription factors through many repeated gene
      duplications accompanied by functional divergence. As the biggest subfamily of
      C2H2 zinc finger protein family, Kruppel-associated box-containing zinc finger
      proteins (KRAB-ZFPs) appeared at the period oftetrapod, expand rapidly along with
      species evolution, and take about 60% of the total C2H2 zinc finger proteins in
      human. During species evolution, the DNA binding ability of KRAB-ZFPs is changed
      while the KRAB-ZFPs-mediate transcriptional repression ability maintains stable
      under the evolution pressure. Moreover, multiple KRAB-ZFPs function
      synergistically with KAP1 on transcriptional silencing of retroelements, and the
      coevolution between KRAB-ZFPs and target retrotransposons restrict the jumping
      ability of the retroelements. In this review, we summarize the roles of KRAB-ZFPs
      duplication, the flexibility of zinc finger structure, transcriptional repression
      of KRAB-ZFPs/KAP1 and retroelement "jump" in promoting the divergence in
      regulatory network, stable genome change and species evolution, in order to
      reveal the characters and functions of KRAB-ZFPs in driving species evolution
      stably.

PMID- 27867148
TI  - Generation, identification, formation mechanism and application of plant
      haploids.
AB  - Haploids are individuals with gametophytic chromosome numbers. Homozygous doubled
      haploids can be quickly gained by genome doubling. Haploids and doubled haploids
      play an important role on crop breeding, mutant screening, gene functional
      analysis, cytological studies, construction of genetic population and so on, and
      have been a research hotspot of plants in recent years. In this review, we
      summarize the production means, identification, the genetic mechanism and the
      applications of haploids and doubled haploids. We hope to provide a reference for
      study and application of haploids and doubled haploids.

PMID- 27867149
TI  - Research progress on identification of QTLs and functional genes involved in salt
      tolerance in soybean.
AB  - The yield of soybean is substantially reduced when the crop is grown in salinity
      affected soil. This review summarizes the progress achieved in defining the
      genetic basis of salinity tolerance. Both forward (uncovering the genetic basis
      of a phenotype by exploiting natural or induced mutations) and reverse (defining
      the phenotype which arises as a result of an altered DNA sequence) genetics
      methods have been used to reveal the function of key salinity response genes.
      Quantitative trait locus analysis has identified six regions of the genome which
      harbor loci influencing salinity tolerance, and positional cloning has succeeded
      in isolating one important salt tolerant gene. Meanwhile the application of the
      genome-wide association study technique has led to the isolation of a second gene
      involved in salinity tolerance. Reverse genetics experiments have highlighted a
      number of salinity response genes, mainly including ion transporter genes and
      transcription factor genes. These studies lay the foundations for understanding
      the mechanistic basis of salinity tolerance in soybean, knowledge of which would
      be essential to enable the breeding of highly salinity tolerant soybean cultivars
      through the use of marker-assisted selection or transgenesis.

PMID- 27867150
TI  - Generation and analysis of the Rett syndrome-associated MeCP2- null rat model.
AB  - MeCP2 mutations are associated with the Rett syndrome (RTT). Currently, there is
      an urgent need for new animal models for RTT as the existing MeCP2 knockout mouse
      models fail to fully mimic the pathogenesis and symptoms of RTT patients. In
      order to investigate the role of MeCP2 in brain development and RTT pathogenesis,
      we aimed to set up the MeCP2-null rat model using the CRISPR/Cas9 technology.
      Firstly we constructed the MeCP2 targeting vector and then microinjected Cas9
      mRNA and sgRNA mixtures into fertilized ova of SD rats. The sgRNA was designed to
      target the exon 2 of MeCP2. Next, knockout rats were confirmed using DNA
      sequencing and Western blotting. Lastly, phenotypes including growth and
      behaviors of MeCP2 knockout rats were analyzed. The results indicated that the
      MeCP2 knockout rats showed body weight loss, anxiety tendency and cognitive
      deficits. The MeCP2-null rat model established in this study recapitulates the
      major symptoms of RTT patients and provides an alternative tool for future
      studies of MeCP2 functions.

PMID- 27867151
TI  - Genetic analysis and gene mapping of the glabrous leaf and hull mutant glr3 in
      rice (Oryza sativa L.).
AB  - We obtained a glabrous leaf and hull mutant from a population of radiation
      mutagenesis of an indica rice cultivar R401. The mutant produced smooth leaves
      and hairless glumes under normal growth conditions. An F2 population was
      developed from a cross between a japonica cultivar Nipponbare and the glabrous
      leaf and hull mutant. By investigating the performance of the F2 population, we
      found that the mutant phenotype was controlled by a single recessive gene,
      temporarily designated GLR3. Bulked segregant analysis (BSA) based on the F2
      mapping population revealed that GLR3 is located on chromosome 6. By analyzing
      417 typical glabrous leaf F2 plants using molecular markers, GLR3 was mapped to a
      0.2 cM interval between InDel markers ID27101 and ID27199, and the physical
      distance between the two markers is 98 kb. Thus we have mapped the gene GLR3, and
      our work will provide basis for future mechanistic analysis of GLR3 function.

PMID- 27867152
TI  - Transmitting characters of individual E chromosomes of Thinopyrum elongatum in
      Triticum turgidum background.
AB  - The transmission patterns of Thinopyrum elongatum chromosomes in the background
      of Triticum turgidum were investigated through cytogenetic and molecular marker
      analysis based on the F2 and F3 plants derived from a cross between Triticum
      trititrigia (AABBEE) and T. turgidum L. ssp. durum (AABB). An additional
      objective was to develop durum-Th. elongatum E chromosome addition lines. Among
      218 F2 plants, individuals with 2n=28 accounted for 41.7%, those with 2n=29
      accounted for 18.3%, and the remaining 40.0% had 2n=31-42. Molecular marker
      analysis of the F2 monosomic addition plants with 2n=29 showed significant
      differences in transmission rate among Th. elongatum chromosomes. Chromosome 1E
      had the highest transmission rates, while 3E and 6E had the lowest. Among F2
      double monosomic addition plants with 2n=30, joint transmission was frequent
      between 1E, 4E, 7E and 5E; 6E was less frequent in joint transmission with other
      chromosomes, while 2E and 3E never transmitted along with other chromosomes.
      Among F3 plants derived from F2 monosomic addition plants, the transmission rates
      of E chromosomes varied widely, from the minimum of 9.1% for 6E to the maximum of
      27.5% for 1E, consistent with observations from F2 plants. A full set of durum
      Th. elongatum 1E-7E monosomic addition lines and several disomic addition lines
      were selected from F3 plants, and all monosomic addition plants were fertile.
      These chromosome E addition lines will be useful intermediate materials for
      developing substitution lines and translocation lines.

PMID- 27867153
TI  - Cultivating the scientific research ability of undergraduate students in teaching
      of genetics.
AB  - The classroom is the main venue for undergraduate teaching. It is worth pondering
      how to cultivate undergraduate's research ability in classroom teaching. Here we
      introduce the practices and experiences in teaching reform in genetics for
      training the research quality of undergraduate students from six aspects: (1)
      constructing the framework for curriculum framework systematicaly, (2) using the
      teaching content to reflect research progress, (3) explaining knowledge points
      with research activities, (4) explaining the scientific principles and
      experiments with PPT animation, (5) improving English reading ability through
      bilingual teaching, and (6) testing students' analysing ability through
      examination. These reforms stimulate undergraduate students' enthusiasm for
      learning, cultivate their ability to find, analyze and solve scientific problems,
      and improve their English reading and literature reviewing capacity, which lay a
      foundation for them to enter the field of scientific research.

PMID- 27867154
TI  - Life Sciences Discovery and Technology Highlights.

PMID- 27867155
TI  - Handgrip Strength Is Positively Associated with Mildly Elevated Serum Bilirubin
      Levels among Community-Dwelling Adults.
AB  - Handgrip strength (HGS) is a useful measure of health-related quality of life and
      general muscle strength. Serum total bilirubin (T-B) may present potential
      beneficial effects in preventing oxidative changes which are associated with a
      risk of metabolic syndrome and the development of cardiovascular disease. Limited
      information is available regarding whether HGS is an independent confounding
      factor for serum T-B. The study participants were 214 men aged 71 +/- 8 (mean +/-
      standard deviation) years and 302 women aged 71 +/- 7 years that were enrolled
      consecutively from among paticipants aged >= 50 years through an annual check-up
      process. We evaluated the relationship between serum T-B and confounding factors
      within each sex. HGS related significantly with serum T-B in both men (r = 0.156,
      p = 0.023) and women (r = 0.173, p = 0.003). Multiple linear regression analysis
      showed that in men, HGS (beta = 0.173) as well as smoking status (beta = -0.147),
      exercise habit (beta = 0.138), low-density lipoprotein cholesterol (beta =
      0.146), and hemoglobin A1c (HbA1c) (beta = -0.198) were significantly and
      independently associated with serum T-B. In women, HGS (beta = 0.159) as well as
      smoking status (beta = -0.116), high-density lipoprotein cholesterol (beta =
      0.159), and HbA1c (beta = -0.161) were significantly and independently associated
      with serum T-B. Multivariate-adjusted serum T-B levels were significantly lower
      in subjects with the lowest HGS level in both sexes. Increased HGS is strongly
      associated with increased serum T-B, independent of confounding factors in both
      sexes.

PMID- 27867156
TI  - Transcriptional Analysis of Intravenous Immunoglobulin Resistance in Kawasaki
      Disease Using an Induced Pluripotent Stem Cell Disease Model.
AB  - BACKGROUND: Approximately 10-20% of Kawasaki disease (KD) patients are resistant
      to intravenous immunoglobulin (IVIG) treatment. Further, these patients are at a
      particularly high risk of having coronary artery abnormalities. The mechanisms of
      IVIG resistance in KD have been analyzed using patient leukocytes, but not
      patient vascular endothelial cells (ECs). The present study clarifies the
      mechanisms of IVIG resistance in KD using an induced pluripotent stem cell (iPSC)
      disease model.Methods and Results:Dermal fibroblasts or peripheral blood
      mononuclear cells from 2 IVIG-resistant and 2 IVIG-responsive KD patients were
      reprogrammed by the episomal vector-mediated transduction of 6 reprogramming
      factors. KD patient-derived iPSCs were differentiated into ECs (iPSC-ECs). The
      gene expression profiles of iPSC-ECs generated from IVIG-resistant and IVIG
      responsive KD patients were compared by RNA-sequencing analyses. We found that
      the expression ofCXCL12was significantly upregulated in iPSC-ECs from IVIG
      resistant KD patients. Additionally, Gene Set Enrichment Analysis (GSEA) revealed
      that gene sets involved in interleukin (IL)-6 signaling were also upregulated.
      CONCLUSIONS: The first iPSC-based model for KD is reported here. Our mechanistic
      analyses suggest thatCXCL12, which plays a role in leukocyte transmigration, is a
      key molecule candidate for IVIG resistance and KD severity. They also indicate
      that an upregulation of IL-6-related genes may be involved in this pathogenesis.

PMID- 27867157
TI  - Effects of Salt Loading on Plasma Osteoprotegerin Levels and Protective Role of
      Potassium Supplement in Normotensive Subjects.
AB  - BACKGROUND: Excess dietary salt is strongly correlated with cardiovascular
      disease, morbidity, and mortality. Conversely, potassium likely elicits favorable
      effects on cardiovascular disorders. In epidemiological studies, increased plasma
      osteoprotegerin (OPG) concentrations are associated with atherosclerosis and
      vascular deaths. Our study was designed to examine the effects of salt intake and
      potassium supplementation on plasma OPG levels in normotensive subjects.Methods
      and Results:The 18 normotensive subjects were selected from a rural community in
      China. They were sequentially maintained on low-salt diet for 7 days (3 g/day,
      NaCl), high-salt diet for 7 days (18 g/day), and high-salt diet with potassium
      supplementation for 7 days (18 g/day of NaCl+4.5 g/day of KCl). High-salt intake
      enhanced plasma OPG levels (252.7+/-13.9 vs. 293.4+/-16.1 pg/mL). This phenomenon
      was abolished through potassium supplementation (293.4+/-16.1 vs. 235.1+/-11.3
      pg/mL). Further analyses revealed that the OPG concentration positively
      correlated with 24-h urinary sodium excretion (r=0.497, P<0.01). By contrast, OPG
      concentration negatively correlated with 24-h urinary potassium excretion
      (r=0.594, P<0.01). CONCLUSIONS: Salt loading can enhance the production of
      circulating OPG. Potassium supplementation can reverse the effects of excessive
      OPG. Our study results may improve our understanding of the roles of salt and
      potassium in the risk of cardiovascular disorders.

PMID- 27867158
TI  - Preprocedural High-Sensitivity C-Reactive Protein Predicts Long-Term Outcome of
      Percutaneous Coronary Intervention.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) has been used to predict
      the risk of adverse cardiac events in patients with coronary artery disease (CAD)
      after percutaneous coronary intervention (PCI). Less is known, however, about the
      association between hs-CRP and long-term outcome after PCI in the Japanese
      population.Methods and Results:We studied 3,039 all-comer patients with CAD who
      underwent their first PCI and had data available for preprocedural hs-CRP at
      Juntendo University between 2000 and 2011. Patients were assigned to tertiles
      based on preprocedural hs-CRP concentration. We evaluated the incidence of major
      adverse cardiac events (MACE) including all-cause death, acute coronary syndrome
      (ACS), and target vessel revascularization (TVR). Patients with higher hs-CRP had
      a higher prevalence of current smoking, chronic kidney disease and ACS, and a
      lower prevalence of statin use. During a median follow-up period of 6.5 years,
      ongoing divergence in MACE with hs-CRP tertile was noted on Kaplan-Meier curves
      (hs-CRP <0.08 mg/L, 26.4%; 0.08-0.25 mg/L, 38.2%; >0.25 mg/L, 45.6%; log-rank
      P<0.001). After adjustment for established cardiovascular risk factors, hs-CRP
      was associated with higher incidence of MACE (hazard ratio [HR], 1.10; 95% CI:
      1.04-1.16, P<0.001) and higher all-cause mortality (HR, 1.14; 95% CI: 1.06-1.22,
      P<0.001). CONCLUSIONS: Preprocedural hs-CRP measurement is clinically useful for
      long-term risk assessment in Japanese patients with established CAD and
      undergoing PCI.

PMID- 27867159
TI  - Culture-Dependent and -Independent Identification of Polyphosphate-Accumulating
      Dechloromonas spp. Predominating in a Full-Scale Oxidation Ditch Wastewater
      Treatment Plant.
AB  - The oxidation ditch process is one of the most economical approaches currently
      used to simultaneously remove organic carbon, nitrogen, and also phosphorus (P)
      from wastewater. However, limited information is available on biological P
      removal in this process. In the present study, microorganisms contributing to P
      removal in a full-scale oxidation ditch reactor were investigated using culture
      dependent and -independent approaches. A microbial community analysis based on
      16S rRNA gene sequencing revealed that a phylotype closely related to
      Dechloromonas spp. in the family Rhodocyclaceae dominated in the oxidation ditch
      reactor. This dominant Dechloromonas sp. was successfully isolated and subjected
      to fluorescent staining for polyphosphate, followed by microscopic observations
      and a spectrofluorometric analysis, which clearly demonstrated that the
      Dechloromonas isolate exhibited a strong ability to accumulate polyphosphate
      within its cells. These results indicate the potential key role of Dechloromonas
      spp. in efficient P removal in the oxidation ditch wastewater treatment process.

PMID- 27867160
TI  - Morphological and Taxonomic Properties of Tokyovirus, the First Marseilleviridae
      Member Isolated from Japan.
AB  - Members of the Marseilleviridae family are large DNA viruses with icosahedral
      particle structures that infect Acanthamoeba cells. The first Marseillevirus to
      be discovered was isolated in 2009. Since then, several other members of the
      Marseilleviridae family have been reported, including Lausannevirus,
      Senegalvirus, Cannes 8 virus, Insectomime virus, Tunisvirus, Melbournevirus, Port
      Miou virus, and Brazilian Marseillevirus, which have been isolated from Europe,
      Africa, Australia, and South America. The morphological and genomic properties of
      a new Marseilleviridae family member, Tokyovirus, discovered in a water/soil
      sample from a Japanese river in Tokyo, were described in the present study.
      Tokyovirus possesses icosahedral particles of up to 200 nm in diameter, as
      revealed by a transmission electron microscopy (TEM) analysis, which form a giant
      virion factory in Acanthamoeba cells. A preliminary genome analysis predicted 487
      coding sequences. A dot plot analysis and phylogenetic analysis using family B
      DNA polymerase, proliferating cell nuclear antigen (PCNA), and DNA-directed RNA
      polymerase alpha subunit genes revealed that Tokyovirus shares similarities with
      Marseillevirus, Melbournevirus, and Cannes 8 virus (Marseilleviridae subclade A),
      but not with Lausannevirus and Port-Miou virus (subclade B), Tunisvirus and
      Insectomime virus (subclade C), or Brazilian Marseillevirus (subclade D),
      suggesting that Tokyovirus has evolved separately from the previously described
      Marseilleviridae members.

PMID- 27867162
TI  - A unique mechanism regulating gene expression in 1-cell embryos.
AB  - After fertilization, the genome of zygotes is transcriptionally silent. The
      timing of the initiation of transcription is species-specific and occurs at the
      mid-1-cell stage in mice. Recent analyses using high-throughput sequencing (HTS)
      have identified thousands of genes transcribed at the 1-cell stage, and the
      pattern of expression among these genes appears to be unique. In this article, we
      show the result of an additional analysis using HTS data from a previous study,
      and present the hypothesis that an extremely loose chromatin structure causes
      promiscuous gene expression in 1-cell embryos.

PMID- 27867161
TI  - Departure from optimal O2 level for mouse trophoblast stem cell proliferation and
      potency leads to most rapid AMPK activation.
AB  - Previous studies showed that cultured mouse trophoblast stem cells (mTSCs) have
      the most rapid proliferation, normal maintenance of stemness/potency, the least
      spontaneous differentiation, and the lowest level of stress-activated protein
      kinase (SAPK) when incubated at 2% O2 rather than at the traditional 20% O2 or
      hypoxic (0.5% and 0% O2) conditions. Switching from 2% O2 induced fast SAPK
      responses. Here we tested the dose response of AMP-activated protein kinase
      (AMPK) in its active form (pAMPK Thr172P) at O2 levels from 20-0%, and also
      tested whether pAMPK levels show similar rapid changes when mTSC cultures were
      switched from the optimal 2% O2 to other O2 conditions. There was a delayed
      increase in pAMPK levels ~6-8 h after switching conditions from 20% to 2%, 0.5%,
      or 0% O2. Altering O2 conditions from 2% to either 20%, 0.5%, or 0% led to rapid
      increase in pAMPK levels within 1 h, similar to the previously reported SAPK
      response in mTSC cells removed from 2% O2. Twelve hours of 0.5% O2 exposure led
      to cell program changes in terms of potency loss and suppressed biosynthesis, as
      indicated by levels of phosphorylated inactive acetyl CoA carboxylase (pACC).
      Phosphorylation of ACC was inhibited by the AMPK inhibitor Compound C. However,
      unlike other stressors, AMPK does not mediate hypoxia-induced potency loss in
      mTSCs. These results suggest an important aspect of stem cell biology, which
      demands rapid stress enzyme activation to cope with sudden changes in external
      environment, e.g., from least stressful (2% O2) to more stressful conditions.

PMID- 27867163
TI  - Anatomical variations of the arterial supply to the adrenal gland in the rat.
AB  - The adrenal gland is an essential endocrine organ for the stress response. The
      functions of this organ may be studied by ligation of the adrenal artery or
      adrenalectomy. However, in prior studies, descriptions of the anatomical
      variations of the adrenal artery were insufficient and inconsistent. Therefore,
      anatomical variations of the arterial supply to the adrenal gland were studied in
      18 male and 18 female Wistar rats by colored latex injection into the arteries.
      The vascularization pattern was categorized into 4 types based on the origin of
      each adrenal artery. The cranial and middle adrenal arteries arose from the
      caudal phrenic artery in Types 1-3, but the caudal adrenal artery emerged from
      the caudal phrenic artery in Type 1, from the renal artery in Type 2 and from the
      abdominal aorta in Type 3. In Type 4, the cranial and middle adrenal arteries
      stemmed from the cranial phrenic artery, and the caudal adrenal artery arose from
      the caudal phrenic artery. The number of adrenal arteries varied from 3 to 11 on
      the left side and from 4 to 12 on the right side, and the total varied from 9 to
      20 (predominantly 14) in each individual. There was no sex difference in the
      vascularization pattern. The results show that more individual variations occur
      in the adrenal arteries of rats than was previously reported. Such variations
      should always be considered when experimental treatments of the rat adrenal gland
      are performed.

PMID- 27867164
TI  - Preface for Special Issue on the Field of the Abdomen.

PMID- 27867165
TI  - Evaluation of a New Motion-correction Algorithm Using On-rigid Registration in
      Respiratory-gated PET/CT Images of Liver Tumors.
AB  - OBJECTIVE: The present study aimed to determine the qualitative and quantitative
      accuracy of the Q.Freeze algorithm in PET/CT images of liver tumors. METHODS: A
      body phantom and hot spheres representing liver tumors contained 5.3 and 21.2
      kBq/mL of a solution containing 18F radioactivity, respectively. The phantoms
      were moved in the superior-inferior direction at a motion displacement of 20 mm.
      Conventional respiratory-gated (RG) and Q.Freeze images were sorted into 6, 10,
      and 13 phase-groups. The SUVave was calculated from the background of the body
      phantom, and the SUVmax was determined from the hot spheres of the liver tumors.
      Three patients with four liver tumors were also clinically assessed by whole-body
      and RG PET. The RG and Q.Freeze images derived from the clinical study were also
      sorted into 6, 10 and 13 phase-groups. Liver signal-to-noise ratio (SNR) and
      SUVmax were determined from the RG and Q.Freeze clinical images. RESULTS: The
      SUVave of Q.Freeze images was the same as those derived from the body phantom
      using RG. The liver SNR improved with Q.Freeze, and the SUVsmax was not
      overestimated when Q.Freeze was applied in both the phantom and clinical studies.
      Q.Freeze did not degrade the liver SNR and SUVmax even though the phase number
      was larger. CONCLUSIONS: Q.Freeze delivered qualitative and quantitative motion
      correction than conventional RG imaging even in 10-phase groups.

PMID- 27867166
TI  - The Usefulness of Using Fiducial Marker in Proton Therapy for Locally Advanced
      Pancreatic Cancer.
AB  - BACKGROUND: Though the dosimetric criteria for the gastrointestinal tract were
      met, late gastrointestinal toxicity was seen in several cases. Therefore, we
      thought that it was caused by the positional variation of gastrointestine
      surrounding pancreatic cancer because of peristalsis. METHOD: They were confirmed
      by CT image regularly. And we evaluated that how much the difference of matching
      methods for correcting the positional variation influenced dose distribution.
      RESULT: The fiducial markers could follow the position of pancreatic cancer and
      the duodenum. But it could reproduce the dose distribution to pancreatic cancer
      and the duodenum. DISCUSSION: In proton therapy, the reproducible improvement of
      the duodenum position did not make the dose of the duodenum same as planning dose
      because the matching of fiducial markers made the positional relations between
      beam compensator and the duodenum change. CONCLUSION: The fiducial markers are
      useful for correcting the position of pancreatic cancer and the duodenum. But in
      proton therapy, it could not reproduce the dose distribution to pancreatic cancer
      and the duodenum.

PMID- 27867167
TI  - Evaluation of Fat Quantification in the Liver Using Dual Energy CT.
AB  - BACKGROUND AND PURPOSE: Recently, the number of patients with nonalcoholic fatty
      liver disease (NAFLD) has been increasing, and some of them progresses to
      cirrhosis and hepatocellular carcinoma. Dual energy CT allows the discrimination
      of substance using monochromatic image (MI), and steatosis exhibit specifically
      the CT value of each energy level. The purpose is to evaluate the fat
      quantification in the liver using spectral HU curve and CT value compare to a
      conventional image diagnosis. METHODS: Dual energy CT and liver biopsy were
      performed in 54 patients between October 2014 and April 2016. The CT value of 40
      keV MI was measured by spectral HU curve setting 3 points ROI on the right and
      left liver. The CT value of 40 keV MI was compared with steatosis area and the
      NAFLD activity score (NAS). Additionally, steatosis area was compared with the
      conventional CT value scan and hepatorenal echo contrast value. RESULTS AND
      DISCUSSION: The CT value of 40 keV MI exhibited a negative correlation for the
      stenosis area (R2=0.619), and NAS (R2=0.147). Steatosis area exhibited
      correlation for the conventional CT value (R2=0.407), and hepatorenal echo
      contrast (R2=0.135). This study suggests that the evaluation of the fat
      quantification in the liver using the spectral HU curve and CT value improved in
      comparison to the conventional image diagnosis.

PMID- 27867168
TI  - Clinical Experience of Dual-phase Cone Beam Computed Tomography during Hepatic
      Arteriography to Apply 3D-DSA.
AB  - We report on the methods and experiences of the dual-phase cone beam computed
      tomography during hepatic arteriography (CBCTHA) to apply the 3D-DSA. A total of
      32 ml contrast medium (150 mgI/ml) was injected at the rate of 2.0 ml/s for 16 s.
      The early phase scan was initiated 10 s after the start of contrast media
      injection. The delayed phase scan was started 40 s after that (24 s after the end
      of CM injection). When using the dual phase CBCTHA, it was able to obtain the
      classical hepatocellular carcinoma (HCC) images same as computed tomography
      during hepatic arteriography (CTHA). In the early phase, the tumor can be highly
      enhanced against the liver parenchyma. In delayed phase, corona enhancement was
      clearly appeared at the liver parenchyma. Of 58 cases of acquisitions, we
      experienced six cases with miss breath holding and 14 cases with over the field
      of view (FOV) due to hepatomegaly. We evaluated the tumor contrast in 18 cases
      because the other 40 cases were not applied to our criteria. The pixel values of
      ROIs on the tumor, coronal enhancement, and liver parenchyma were measured,
      respectively. Then, we calculated tumor-parenchyma contrast (T-P contrast),
      corona-tumor contrast (C-T contrast), and corona-parenchyma contrast (C-P
      contrast). The T-P contrast was 358+/-112, the C-T contrast was 132+/-51, and the
      C-P contrast was 168+/-66. The contrast was clearly visualized among them. The
      dual-phase CBCTHA that applies the 3D-DSA is a simple and useful technique for
      hepatocellular carcinoma treatment.

PMID- 27867169
TI  - Optimization of the Timing of the Portal Venous Phase in Preoperative 3DCT for
      Malignant Liver Tumors.
AB  - Preoperative three-dimensional computed tomography (3DCT) of the liver is the
      most important examination in performing preoperative simulation. Detailed
      visualization of the portal vein using the workstation is critical to enable
      accurate liver segmentation. However, the timing of imaging in the portal venous
      phase has mostly been reported equivalent to that of the liver screening
      examinations commonly performed. The purpose of this study was to examine the
      optimal timing of image capture to create the best portal vein visualization in
      preoperative 3DCT of the liver. Seventy-nine patients who underwent hepatectomy
      for malignant liver tumors were enrolled in this study. All patients were
      preoperatively examined using protocol A (imaging method separated into a portal
      venous phase and a hepatic venous phase) and then examined 1 week after surgery
      using protocol B (normal liver screening protocol). We first established the
      regions of interest in the portal vein and the hepatic vein and then compared CT
      values for these regions under protocol A and protocol B. The average CT value of
      the portal vein in protocol A and B was 239.8+/-28.1 HU and 202.2+/-18.5 HU,
      respectively. The average CT value of the portal vein in protocol A was
      significantly higher compared with protocol B (p<0.01). By introducing separate
      timing for portal venous phase imaging before preoperative 3DCT (protocol A), it
      is possible to satisfactorily depict the portal vein.

PMID- 27867170
TI  - Evaluation of Appropriate Readout Sequence for Renal MRI Perfusion Using ASTAR
      (ASL) Technique.
AB  - The aim of this study was to compare true-steady state free precession (True
      SSFP) with fast field echo (FFE) as readout imaging sequences for renal arterial
      spin labeling (ASL), and to optimize the imaging condition. Renal ASL perfusion
      images were acquired using signal targeting with alternated radio frequency using
      asymmetric inversion slab (ASTAR) technique with respiratory triggering at 3T MRI
      system, using either 3D True-SSFP or FFE as the readout sequence. Inversion time
      (TI) varied from 800 to 2400 ms. Appropriate flip angles were estimated for each
      sequence by simulating signal intensity (SI). The SI of the renal cortex,
      vertebral body, and intestinal tract were measured, and the contrast ratio of the
      cortex (CRcortex) or intestine (CRintestine) related to vertebra was calculated.
      The image quality of the kidneys, background signal suppression, and
      misregistration were evaluated by four-point scales. As a result, in quantitative
      evaluation, the average of CRcortex of each TI (800, 1200, 1600, 2000, and 2400
      msec) were 0.49, 0.57, 0.63, 0.63, and 0.56 in FFE, and 0.59, 0.71, 0.73, 0.73,
      and 0.68 in True-SSFP, respectively. IN qualitative evaluation, ASL images with
      True-SSFP readout were significantly better than those with FFE readout. In
      conclusion, True-SSFP sequences will be recommended as read out imaging sequence
      for obtaining ASL image compared with FFE image.

PMID- 27867171
TI  - Optimal Imaging Parameters and the Advantage of Renal Artery Image Using Time
      spatial Labeling Inversion Pulse at 3 Tesla Magnetic Resonance Imaging:
      Comparison of Image Quality for 1.5 Tesla Magnetic Resonance Imaging.
AB  - With the recent spread of three tesla (3 T) magnetic resonance imaging (MRI),
      time-spatial labeling inversion pulse (Time-SLIP) technique at high magnetic
      field can be used. The purpose of this study was to determine appropriate renal
      artery imaging parameters and to compare with the 1.5 T MRI image quality of a
      renal artery using the Time-SLIP technique. The imaging sequence was 3D true
      steady-state free precession (True SSFP), and using respiratory gated by the
      voice instructions of breath interval 2, 4, 6 seconds. We measured the fat
      signals when changing the values of short TI inversion recovery (STIR TI), the
      renal artery and renal parenchyma signals when changing the values of black blood
      time interval (BBTI), and contrast-to-noise ratio (CNR) between renal artery and
      background in 11 healthy volunteers. Visual evaluation using a 4-stage score at
      renal artery in clinical cases was performed. 3 T MRI is compared with a 1.5 T
      MRI, and the null point of STIR TI value is 60 ms extension, null point of BBTI
      value in the renal parenchyma was an extension of 250 ms in any of the breath
      interval. In flow effect, there is no difference in the 1.5 T MRI and 3 T MRI,
      peaked at BBTI value 1500 ms. CNR and visual evaluation were better than 3 T MRI.
      3 T MRI showed a better image quality by the background signal suppression effect
      of the extension of the T1 value.

PMID- 27867172
TI  - Evaluation of Image Quality in Three-dimensional Fat-suppressed T1-weighted
      Images with Fast Acquisition Mode for Upper Abdomen.
AB  - We compared the uniformity of fat-suppression and image quality using three
      dimensional fat-suppressed T1-weighted gradient-echo sequences that are liver
      acquisition with volume acceleration (LAVA) and Turbo-LAVA at 3.0T-MRI. The
      subjects were seven patients with liver disease (mean age, 66.7+/-8.2 years). The
      axial slices of two LAVA sequences were used for the comparison of the uniformity
      of fat-suppression and image quality at a region-of-interest (ROI) of the liver
      dome, the porta, and the renal hilum. To yield a quantitative measurement of the
      uniformity of fat suppression, the percentage standard deviation (%SD) was
      calculated by comparing two sequences. For image signal to noise ratio (SNR), the
      contrast between the liver and fat (Cliver-fat), and the liver and muscle (Cliver
      muscle), the other ROIs were placed in the superficial fat, liver, spleen,
      pancreas, and muscle. The %SD in Turbo-LAVA (28.1+/-16.8%) was lower than that in
      LAVA (41.5+/-13.4%). The SNRs in Turbo-LAVA (17.8+/-4.1 [liver], 12.5+/-3.0
      [pancreas], 14.7+/-1.6 [spleen], 8.2+/-3.5 [fat]) were lower than those in LAVA
      (20.9+/-6.1 [liver], 16.8+/-4.1 [pancreas], 17.4+/-2.4 [spleen], 12.0+/-4.5
      [fat]). While, the Cliver-fat in the Turbo-LAVA (0.72+/-0.06) was significantly
      higher than that in LAVA (0.59+/-0.07). Turbo-LAVA sequence offers superior and
      more homogenous fat-suppression in comparison to LAVA sequence.

PMID- 27867174
TI  - Operator Dose Measurements and Image Quality Assessment in Computed Tomography
      Fluoroscopy Using Bismuth Sheet.
AB  - OBJECTIVE: The purpose of this study was to assess the dose reduction and the
      image quality using bismuth sheets during the computed tomography fluoroscopy
      (CTF). MATERIALS AND METHODS: The bismuth sheets of 1-mm thick were put on the
      upper mylar ring to reduce the frontal X-ray. The dose rates of an operator were
      measured using a torso phantom in the patient position during the CTF. The torso
      phantom was set on the gantry rotation center (center) and the lower position
      from the center (off-center). The image quality of the CTF image was assessed
      using an original phantom that mimics the normal liver parenchyma and the low
      attenuation lesions. The image contrast and contrast-to-noise ratio (CNR) were
      compared with and without the bismuth sheets. RESULTS: The bismuth sheets reduced
      the dose rate of the operator, regardless of whether the torso phantom was set at
      the center or the off-center. The reduction rate of exposure at the center and
      the off-center were 42.3% and 34.5%, respectively. There were no significant
      differences in the image contrast and the CNR, although the bismuth sheets
      increased the CT values of the liver parenchyma and the low attenuation lesions.
      CONCLUSION: The bismuth sheets were effective for the reduction of exposure to
      the operator without degrading the image quality of CTF images.

PMID- 27867175
TI  - Understanding the Scatter Radiation Distribution during C-arm CT Examination: A
      Body Phantom Study.
AB  - The purpose of this study was to understand the scatter radiation distribution
      during C-arm CT examination in the interventional radiography (IVR) room to show
      the escaped area and the radiation protective method. The C-arm rotates 200
      degrees  in 5 s. The tube voltage was 90 kV, and the entrance dose to the
      detector was 0.36 MUGy/frame during C-arm CT examination. The scattered doses
      were measured each 50 cm from the isocenter like a grid pattern. The heights of
      the measurement were 50, 100, and 150 cm from the floor. The maximum scattered
      doses were 38.23+/-0.60 MUGy at 50 cm, 43.86+/-0.20 MUGy at 100 cm, and 25.78+/
      0.37 MUGy at 150 cm. The scatter radiation distribution at 100 cm was the highest
      scattered dose. The operator should protect their reproductive gland, thyroid,
      and lens. The scattered dose was low behind the C-arm body and the bed, so they
      will be able to become the escaped area for staff.

PMID- 27867173
TI  - Evaluation of In Vivo Volumetric Dosimetry for Prostate Cancer Using Electronic
      Portal Imaging Device.
AB  - PURPOSE: Volumetric modulated arc therapy (VMAT) is capable of acquiring
      projection images using electronic portal imaging device (EPID). Commercial EPID
      based dosimetry software, dosimetry check (DC), allows in vivo dosimetry using
      projection images. The purpose of this study was to evaluate in vivo dosimetry
      for prostate cancer using VMAT. METHOD: VMAT plans were generated for eight
      patients with prostate cancer using treatment planning system (TPS), and patient
      quality assurances (QAs) were carried out with phantom. We analyzed five plans as
      phantom study and five plans as patient study. Projection images were acquired
      during VMAT delivery. DC converted acquired images into fluence images and used a
      pencil beam algorithm to calculate dose distributions delivered on the CT images
      of the phantom and the patients. We evaluated isocenter point doses and gamma
      analysis in both studies and dose indexes of planning target volume (PTV),
      bladder and rectum in patient study. RESULTS AND DISCUSSION: Dose differences at
      the isocenter were less than a criterion in both studies. Pass rates of the gamma
      analysis were less than a criterion by two plans in the phantom study. Dose
      indexes of reconstructed distribution were lower than original plans and standard
      deviations of PTV in reconstructed distribution were larger than original plans.
      The errors were caused by some issues, such as the commissioning of DC,
      variations in patient anatomy, and patient positioning. CONCLUSION: The method
      was feasible to non-invasively perform in vivo dose evaluation for prostate
      cancer using VMAT.

PMID- 27867176
TI  - Impact of Pelvic Rotational Setup Error on Lymph Nodal Dose in Whole Pelvic IMRT
      Using Fiducial Markers.
AB  - PURPOSE: The aim of this study was to investigate the impact of pelvic rotational
      setup error on lymph nodal dose in the whole pelvic intensity-modulated radiation
      therapy using the fiducial marker. METHODS: The dose differences of clinical
      target volume for pelvic lymph node (CTVLN) due to isocenter (IC) shift and
      pelvic rotation were evaluated using the radiation treatment planning system. The
      rotated computed tomography (CT) images were created for the simulation of the
      pelvic rotation. The original CT images were rotated around the IC of the
      original plan in the pitch and roll directions up to+/-3.0 deg. at 1.0 deg.
      intervals. As simulated plans, IC positions were shifted in the anterior
      posterior and superior-inferior directions up to+/-10 mm at 2 mm intervals in the
      original and rotated CT images, and the dose distributions were calculated. The
      dose calculation was performed for each CT image while keeping the movement of
      multi leaf collimator and the monitor unit of the original plan. The differences
      between D98% of CTVLN in the original plan and simulated plans were calculated.
      RESULTS: In the posterior direction shifts of 4, 6, 8, and 10 mm, the dose
      reduction of 0.7, 2.1, 6.1, and 11.9% from the original plan were found for D98%
      of CTVLN, respectively. The dose reductions due to the rotation of pitch
      direction were greater than the rotation of roll direction. In the posterior
      direction shifts of 4, 6, 8, and 10 mm with 3.0 deg. rotation of pitch direction,
      the dose reduction of 2.2, 6.8, 12.8, and 19.0% from the original plan were
      found, respectively. CONCLUSION: The dose reduction of CTVLN might be occurred
      due to the rotational setup error of pitch direction.

PMID- 27867177
TI  - Image Quality Characteristics of the 3D-parallel Imaging Method (CAIPIRINHA) in
      Abdominal MRI.
AB  - This study investigated the image quality using controlled aliasing in parallel
      imaging results in higher acceleration (CAIPIRINHA) to shorten the imaging time
      in dynamic abdominal examinations. Comparisons with the conventional generalized
      autocalibrating partially parallel acquisitions (GRAPPA) method were made by
      changing the sampling shift in CAIPIRINHA using a 3.0 T MRI. The measurements
      included the visual evaluation of five stages, the signal-to-noise ratio (SNR),
      and contrast-to-noise ratio (CNR) in phantom experiments. The visual evaluation
      (five stages) and SNR were determined using a nickel sulfate bottle phantom
      attached to the MRI device. Each evaluation was performed on the middle slice of
      the 3D image. The SNR was compared with the mean region of interest value
      calculated from five locations within the phantom. The CNR was determined using
      custommade phantoms that mimic the T1 and T2 values of the liver and spleen. In
      the results, at reduction factor (Rf) = 6 and 8, the SNR per unit imaging time
      was reduced with GRAPPA, while there was no decrease in SNR and CNR with
      CAIPIRINHA. By performing imaging using an appropriate sampling shift, it is
      possible to acquire an equivalent GRAPPA in a short period of time using
      CAIPIRINHA.

PMID- 27867178
TI  - MTF Measurement of MR Blurring in Liver Dynamic MRI with Gd-EOB-DTPA.
AB  - During the arterial phase acquisition of Gd-EOB-DTPA examinations, use of a small
      volume of the Gd-EOB-DTPA may make it difficult the encoding center of the k
      space, and produce blurring. The previous studies revealed the encoding technique
      of the k-space was one of the most important reasons. However, there is no report
      to discuss the reasons with quantitative evaluations. The purpose of this study
      was to quantitatively evaluate the characteristics of the artifacts using
      different k-space encoding techniques (centric-view ordering (CVO) and sequential
      view ordering (SVO)) for liver dynamic MRI in computer simulation study. This
      simulation study consists of the following steps. First of all, the creation of a
      time intensity curve, and original simulation images at certain points among the
      one phase dynamic scanning. Secondly, creation-simulated MR echo data from the
      created original images using FFT, and encoding simulated k-space using the
      simulated MR echo data. Finally, a reconstruction of simulated dynamic MR images
      from the simulated k-space, and to evaluate each simulated MR images, we measured
      modulation transfer functions (MTFs) from the bar patterns of the reconstructed
      images. The results of the CVO simulation indicated that the bar patterns were
      blurring compared to the images encoded by the SVO. The results of the SVO
      simulation indicated that the bar patterns were not enhanced at late scan
      timings. In addition, the results of MTFs indicated that there was no edge
      enhancement at all scan timings and both encoding techniques. In conclusion, it
      is possible to quantitatively evaluate the characteristics of artifacts using
      MTF, which was measured by the bar patterns, in liver dynamic MRI.

PMID- 27867179
TI  - Required Work for a Radiology Technologist in IR.

PMID- 27867180
TI  - Ultrasound Examination of the Abdomen.

PMID- 27867181
TI  - IMDRF/DITTA Activity for Harmonization and Convergence of Medical Device
      Regulations.

PMID- 27867182
TI  - To Support Safety and High Quality Medical Service from the Aspect of the
      Radiation Technology.

PMID- 27867183
TI  - Serum Calcium and Risk of Nonmedullary Thyroid Cancer in Patients with Primary
      Hyperparathyroidism.
AB  - BACKGROUND Clinical cases of nonmedullary thyroid carcinoma (NMTC) in combination
      with primary hyperparathyroidism (PHPT) have been reported occasionally. However,
      the clinical characteristics and risk factors of concomitant NMTC in PHPT
      patients remain unclear. This study aimed to assess the association between PHPT
      and NMTC, and evaluate the clinical characteristics and risk factors of NMTC in
      Chinese patients with PHPT. MATERIAL AND METHODS This was a retrospective cohort
      analysis. We reviewed the medical records of 155 patients who underwent surgery
      for PHPT in two large medical centers in China between 2009 and 2014. The
      clinical manifestations, biochemical abnormalities, and histological
      characteristics of PHPT patients were analyzed. RESULTS Of the 155 patients with
      PHPT, 58 patients (37.4%) had thyroid nodules and 12 patients (7.7%) were ill
      with concomitant NMTC. PHPT patients with NMTC demonstrated significantly lower
      preoperative serum calcium levels compared to PHPT patients with benign thyroid
      nodules (p<0.05). A significantly negative association between preoperative serum
      calcium levels and the presence of NMTC was found in PHPT patients (p<0.05).
      Furthermore, ROC analysis revealed that albumin-corrected serum calcium levels
      <2.67 mmol/L had good capacity to differentiate the PHPT patients with NMTC from
      those with benign thyroid nodules. CONCLUSIONS Compared with the reported much
      lower prevalence of thyroid carcinoma in the general population, our results
      suggest that PHPT might be a risk factor for the malignancy of thyroid nodules; a
      lower level of serum calcium may predict the existence of NMTC in PHPT patients
      with thyroid nodules.

PMID- 27867184
TI  - A Rare Case of Tubulointerstitial Nephritis and Uveitis Syndrome Treated with a
      Multi-Specialty Approach.
AB  - BACKGROUND It is important for an ophthalmologist and nephrologist to look for
      hidden causes of uveitis and nephritis, respectively. Delay in diagnosis leads to
      increased morbidity and failure to systemically manage the patient results in
      future recurrence of disease. It is likely that TINU remains underdiagnosed and
      could potentially account for some of the cases of idiopathic uveitis, especially
      when greater than 50% of uveitis cases have no identifiable cause. Fewer than 300
      cases of tubulointerstitial nephritis and uveitis (TINU) syndrome have been
      reported. In TINU syndrome, inflammation affects the renal tubules, interstitial
      tissue, and uveal tract. Its pathogenesis remains poorly understood. CASE REPORT
      We report a rare case of TINU syndrome in a 23-year-old female who was treated
      using a multispecialty approach. Her primary care physician diagnosed her with
      proteinuria and acute kidney injury and referred her to the nephrologist, who
      later referred her to the ophthalmologist. A left kidney biopsy confirmed acute
      interstitial nephritis. Following the discovery of a "pink eye", the patient was
      referred to ophthalmology and diagnosed with anterior uveitis, confirming TINU
      syndrome. Without the additional findings of uveitis, the diagnosis would have
      been missed. Resolution was obtained through steroid therapy. CONCLUSIONS
      Correctly diagnosing TINU syndrome requires a multispecialty approach and may not
      be obvious upon initial presentation. Therefore, the ophthalmologist needs to
      consider TINU in the differential diagnosis for a patient with bilateral uveitis
      and evaluate a urinalysis for proteinuria as part of the work up.

PMID- 27867185
TI  - Absorption mechanism of DHP107, an oral paclitaxel formulation that forms a
      hydrated lipidic sponge phase.
AB  - Paclitaxel is a most widely used anticancer drug with low oral bioavailability,
      thus it is currently administered via intravenous infusion. DHP107 is a lipid
      based paclitaxel formulation that can be administered as an oral solution. In
      this study, we investigated the mechanism of paclitaxel absorption after oral
      administration of DHP107 in mice and rats by changing the dosing interval, and
      evaluated the influence of bile excretion. DHP107 was orally administered to mice
      at various dosing intervals (2, 4, 8, 12, 24 h) to examine how residual DHP107
      affected paclitaxel absorption during subsequent administration. Studies with
      small-angle X-ray diffraction (SAXS) and cryo-transmission electron microscopy
      (cryo-TEM) showed that DHP107 formed a lipidic sponge phase after hydration. The
      AUC values after the second dose were smaller than those after the first dose,
      which was correlated to the induction of expression of P-gp and CYP in the livers
      and small intestines from 2 h to 7 d after the first dose. The smaller AUC value
      observed after the second dose was also attributed to the intestinal adhesion of
      residual formulation. The adhered DHP107 may have been removed by ingested food,
      thus resulting in a higher AUC. In ex vivo and in vivo mucoadhesion studies, the
      formulation adhered to the villi for up to 24 h, and the amount of DHP107 that
      adhered was approximately half that of monoolein. The paclitaxel absorption after
      administration of DHP107 was not affected by bile in the cholecystectomy mice.
      The dosing interval and food intake affect the oral absorption of paclitaxel from
      DHP107, which forms a mucoadhesive sponge phase after hydration. Bile excretion
      does not affect the absorption of paclitaxel from DHP107 in vivo.

PMID- 27867186
TI  - Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against
      colorectal cancers via improving their subcellular distribution.
AB  - Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly
      made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary
      heart disease and tumors by boosting Qi and nourishing Yin. In this study we
      examined whether SMI could produce direct synergetic effects on the cytoxicity of
      adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro,
      and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with
      LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg.kg
      1.3d-1) or PTX (7.5 mg.kg-1.3d-1) with or without SMI (0.01 mL.g-1.d-1) for 13 d.
      Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of
      ADR and PTX, whereas administration of SMI alone at the given dosage did not
      produce visible anti-cancer effects, The chemosensitizing action of SMI was
      associated with increased concentrations of ADR and PTX in the plasma and tumors.
      In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 MUL/mL) significantly
      enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable
      pharmacokinetic changes in the subcellular distribution of ADR and PTX. In
      addition, SMI-induced intracellular accumulation of ADR was closely correlated
      with the increased expression levels of P-glycoprotein in 4 colon cancer cell
      lines (r2=+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon
      cancers in vivo and in vitro by improving the subcellular distributions of ADR
      and PTX.

PMID- 27867187
TI  - Crosstalk of ROS/RNS and autophagy in silibinin-induced apoptosis of MCF-7 human
      breast cancer cells in vitro.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important
      roles in regulating cell survival and death. Silibinin is a natural polyphenolic
      flavonoid isolated from milk thistle with anti-tumor activities, but it was found
      to induce cytoprotective ROS/RNS in human breast cancer MCF-7 cells. Furthermore,
      treatment with silibinin down-regulates ERalpha expression in MCF-7 cells, and
      inducing both autophagy and apoptosis. In this study we explored the relationship
      between ER-associated pathways and RNS/ROS in MCF-7 cells. We also investigated
      the molecular mechanisms underlying the reciprocal regulation between ROS/RNS
      levels and autophagy in the death signaling pathways in silibinin-treated MCF-7
      cells. Silibinin (100-300 MUmol/L) dose-dependently increased ROS/RNS generation
      in MCF-7 cells (with high expression of ERalpha and low expression of ERbeta) and
      MDA-MB-231 cells (with low expression of ERalpha and high expression of ERbeta).
      Scavenging ROS/RNS significantly enhanced silibinin-induced death of MCF-7 cells,
      but not MDA-MB231 cells. Pharmacological activation or blockade of ERalpha in MCF
      7 cells significantly enhanced or decreased, respectively, silibinin-induced
      ROS/RNS generation, whereas activation or block of ERbeta had no effect. In
      silibinin-treated MCF-7 cells, exposure to the ROS/RNS donators decreased the
      autophagic levels, whereas inhibition of autophagy with 3-MA significantly
      increased ROS/RNS levels. We further showed that increases in ROS/RNS generation,
      ERalpha activation or autophagy down-regulation had protective roles in silibinin
      treated MCF-7 cells. Under a condition of ERalpha activation, scavenging ROS/RNS
      or stimulating autophagy enhanced the cytotoxicity of silibinin. These results
      demonstrate the existence of two conflicting pathways in silibinin-induced death
      of MCF-7 cells: one involves the down-regulation of ERalpha and thereby
      augmenting the pro-apoptotic autophagy downstream, leading to cell death; the
      other involves the up-regulation of pro-survival ROS/RNS; and that the generation
      of ROS/RNS and autophagy form a negative feedback loop whose balance is regulated
      by ERalpha.

PMID- 27867188
TI  - A historic study that opened a new chapter in nutritional science.

PMID- 27867190
TI  - Hypertension: Microbiota under pressure.

PMID- 27867191
TI  - Sepsis: Preventing organ failure in sepsis - the search continues.

PMID- 27867192
TI  - DNA repair: RNA-DNA hybrids: double-edged swords.

PMID- 27867189
TI  - The role of phosphate in kidney disease.
AB  - The importance of phosphate homeostasis in chronic kidney disease (CKD) has been
      recognized for decades, but novel insights - which are frequently relevant to
      everyday clinical practice - continue to emerge. Epidemiological data
      consistently indicate an association between hyperphosphataemia and poor clinical
      outcomes. Moreover, compelling evidence suggests direct toxicity of increased
      phosphate concentrations. Importantly, serum phosphate concentration has a
      circadian rhythm that must be considered when interpreting patient phosphate
      levels. Detailed understanding of dietary sources of phosphate, including food
      additives, can enable phosphate restriction without risking protein malnutrition.
      Dietary counselling provides an often underestimated opportunity to target the
      increasing exposure to dietary phosphate of both the general population and
      patients with CKD. In patients with secondary hyperparathyroidism, bone can be an
      important source of serum phosphate, and adequate appreciation of this fact
      should impact treatment. Dietary and pharmotherapeutic interventions are
      efficacious strategies to lower phosphate intake and serum concentration.
      However, strong evidence that targeting serum phosphate improves patient outcomes
      is currently lacking. Future studies are, therefore, required to investigate the
      effects of modern dietary and pharmacological interventions on clinically
      meaningful end points.

PMID- 27867193
TI  - From profiles to function in epigenomics.
AB  - Myriads of epigenomic features have been comprehensively profiled in health and
      disease across cell types, tissues and individuals. Although current epigenomic
      approaches can infer function for chromatin marks through correlation, it remains
      challenging to establish which marks actually have causative roles in gene
      regulation and other processes. After revisiting how classical approaches have
      addressed this question in the past, we discuss the current state of epigenomic
      profiling and how functional information can be indirectly inferred. We also
      present new approaches that promise definitive functional answers, which are
      collectively referred to as 'epigenome editing'. In particular, we explore CRISPR
      based technologies for single-locus and multi-locus manipulation. Finally, we
      discuss which level of function can be achieved with each approach and introduce
      emerging strategies for high-throughput progression from profiles to function.

PMID- 27867196
TI  - Extracellular ADP facilitates monocyte recruitment in bacterial infection via ERK
      signaling.
AB  - As the most prominent clinical drug targets for the inhibition of platelet
      aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both
      platelets and macrophages. However, the roles and function of P2Y12/13 in the
      regulation of macrophage-mediated innate immune responses remain unclear. Here,
      we demonstrate that adenosine 5'-diphosphate (ADP), the endogenous ligand of
      P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from
      macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4.
      Furthermore, the expression of P2Y13 was clearly increased in both LPS-treated
      macrophages and tuberculosis patients. ADP protected mice from E. coli 0111
      induced peritonitis by recruiting more macrophages to the infected sites.
      Consistent with this, ADP and ADP-treated cell culture medium attracted more
      macrophages in the transwell assay by enhancing the expression of MCP-1.
      Nevertheless, P2Y1 is dispensable for ADP-mediated protection against bacterial
      infection. However, either P2Y12/P2Y13 deficiency or blocking the downstream
      signaling of P2Y12/P2Y13 blocked the ADP-mediated immune response and allowed
      more bacteria to persist in the infected mice. Furthermore, extracellular signal
      regulated kinase (ERK) phosphorylation was clearly increased by ADP, and this
      type of activation could be blocked by either forskolin or analogs of cyclic AMP
      (cAMP) (for example, 8-bromo-cAMP). Accordingly, ADP-induced MCP-1 production and
      protection against bacterial infection could also be reduced by U0126, forskolin
      and 8-bromo-cAMP. Overall, our study reveals a relationship between danger
      signals and innate immune responses, which suggests the potential therapeutic
      significance of ADP-mediated purinergic signaling in infectious diseases.

PMID- 27867194
TI  - Regulatory activities of transposable elements: from conflicts to benefits.
AB  - Transposable elements (TEs) are a prolific source of tightly regulated,
      biochemically active non-coding elements, such as transcription factor-binding
      sites and non-coding RNAs. Many recent studies reinvigorate the idea that these
      elements are pervasively co-opted for the regulation of host genes. We argue that
      the inherent genetic properties of TEs and the conflicting relationships with
      their hosts facilitate their recruitment for regulatory functions in diverse
      genomes. We review recent findings supporting the long-standing hypothesis that
      the waves of TE invasions endured by organisms for eons have catalysed the
      evolution of gene-regulatory networks. We also discuss the challenges of
      dissecting and interpreting the phenotypic effect of regulatory activities
      encoded by TEs in health and disease.

PMID- 27867197
TI  - p38alpha has an important role in antigen cross-presentation by dendritic cells.
AB  - The role of the p38 signaling pathway in the innate and adaptive immune responses
      has been well documented, especially in inflammatory cytokine production by
      dendritic cells (DCs). However, whether the p38 signaling pathway affects the
      important antigen (Ag) presentation function of DCs remains largely unknown. In
      this study, we reported that the deletion of p38alpha resulted in an impaired
      cross-presentation ability of CD8+ conventional DCs (cDCs) and a reduction in the
      direct presentation ability of CD8- cDCs ex vivo. Further study revealed that
      p38alpha had a crucial role in Ag processing by CD8+ cDCs but did not affect the
      Ag uptake or co-stimulation of T cells. Moreover, p38alpha deficiency led to
      reduced cross-priming of T cells in vivo. The production of the IL-12p40 and IL
      12p70 cytokines by p38alpha-deficient cDCs was also significantly reduced. Our
      study identified a new role for p38alpha in modulating the important antigen
      cross-presentation function of DCs.

PMID- 27867195
TI  - Order from clutter: selective interactions at mammalian replication origins.
AB  - Mammalian chromosome duplication progresses in a precise order and is subject to
      constraints that are often relaxed in developmental disorders and malignancies.
      Molecular information about the regulation of DNA replication at the chromatin
      level is lacking because protein complexes that initiate replication seem to bind
      chromatin indiscriminately. High-throughput sequencing and mathematical modelling
      have yielded detailed genome-wide replication initiation maps. Combining these
      maps and models with functional genetic analyses suggests that distinct DNA
      protein interactions at subgroups of replication initiation sites (replication
      origins) modulate the ubiquitous replication machinery and supports an emerging
      model that delineates how indiscriminate DNA-binding patterns translate into a
      consistent, organized replication programme.

PMID- 27867200
TI  - Antifungals: Uncovering new drugs and targets.

PMID- 27867198
TI  - Probing the evolution, ecology and physiology of marine protists using
      transcriptomics.
AB  - Protists, which are single-celled eukaryotes, critically influence the ecology
      and chemistry of marine ecosystems, but genome-based studies of these organisms
      have lagged behind those of other microorganisms. However, recent transcriptomic
      studies of cultured species, complemented by meta-omics analyses of natural
      communities, have increased the amount of genetic information available for
      poorly represented branches on the tree of eukaryotic life. This information is
      providing insights into the adaptations and interactions between protists and
      other microorganisms and macroorganisms, but many of the genes sequenced show no
      similarity to sequences currently available in public databases. A better
      understanding of these newly discovered genes will lead to a deeper appreciation
      of the functional diversity and metabolic processes in the ocean. In this Review,
      we summarize recent developments in our understanding of the ecology, physiology
      and evolution of protists, derived from transcriptomic studies of cultured
      strains and natural communities, and discuss how these novel large-scale genetic
      datasets will be used in the future.

PMID- 27867201
TI  - Does body mass index modify the association between physical activity and screen
      time with cardiometabolic risk factors in adolescents? Findings from a country
      wide survey.
AB  - BACKGROUND: Moderate and vigorous physical activity (MVPA) and screen time (ST)
      have been associated with cardiometabolic health in youth. However, previous
      studies are conflicting whether these associations are independent of each other
      and it is unknown if they are modified by adiposity. We aimed to examine the
      independent and joint associations between MVPA and ST with cardiometabolic risk
      across body mass index (BMI) categories. METHODS: A total of 36 956 Brazilian
      adolescents (12-17 years) from the Study of Cardiovascular Risks in Adolescents
      were included. Information on time spent in MVPA and ST were assessed by self
      reports. Blood pressure, Homeostasis Model Assessment of Insulin Resistance,
      triglycerides, high-density lipoprotein-cholesterol and waist circumference were
      used to calculate a cardiometabolic risk score (sex-age-specific top-risk
      quintile for each biomarker). Ordered logistic regression was used to examine the
      associations. RESULTS: In final adjusted models, both higher MVPA (proportional
      odds ratio (POR)=0.80; 95% confidence interval (CI): 0.67-0.95) and ST (POR=1.23;
      95% CI: 1.10-1.37) were independently associated with cardiometabolic risk. After
      stratification by normal weight vs overweight/obese, the inverse independent
      association for MVPA remained unchanged, whereas ST was positively associated
      with cardiometabolic risk only in overweight/obese adolescents (POR=1.62; 95% CI:
      1.18-2.22). Participants who met the recommendations for both MVPA and ST had
      lower odds for cardiometabolic risk, especially if they were overweight/obese
      (POR=0.46; 95% CI: 0.31-0.68). CONCLUSIONS: MVPA and ST are independently
      associated with cardiometabolic risk; the association with ST, however, appears
      modified by BMI. Normal-weight adolescents should be encouraged to increase MVPA,
      whereas a combination of increasing MVPA and decreasing ST is recommended in
      those who are overweight or obese.

PMID- 27867199
TI  - Candida albicans cell-type switching and functional plasticity in the mammalian
      host.
AB  - Candida albicans is a ubiquitous commensal of the mammalian microbiome and the
      most prevalent fungal pathogen of humans. A cell-type transition between yeast
      and hyphal morphologies in C. albicans was thought to underlie much of the
      variation in virulence observed in different host tissues. However, novel yeast
      like cell morphotypes, including opaque(a/alpha), grey and gastrointestinally
      induced transition (GUT) cell types, were recently reported that exhibit marked
      differences in vitro and in animal models of commensalism and disease. In this
      Review, we explore the characteristics of the classic cell types - yeast, hyphae,
      pseudohyphae and chlamydospores - as well as the newly identified yeast-like
      morphotypes. We highlight emerging knowledge about the associations of these
      different morphotypes with different host niches and virulence potential, as well
      as the environmental cues and signalling pathways that are involved in the
      morphological transitions.

PMID- 27867203
TI  - Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin
      resistance.
AB  - BACKGROUND: The exchange protein directly activated by cAMP (Epac), which is
      primarily involved in cAMP signaling, has been known to be essential for
      controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The
      function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice.
      However, the role of Epac2 in obesity remains unclear. METHODS: To evaluate the
      role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed
      in neurons and endocrine tissues. Physiological factors related to obesity were
      analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin
      levels, energy expenditure, glucose tolerance, and insulin and leptin resistance.
      To determine the mechanism of Epac2a, mice received exogenous leptin and then
      hypothalamic leptin signaling was analyzed. RESULTS: Epac2a KO mice appeared to
      have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but
      an early onset increase of plasma leptin levels and decrease of plasma
      adiponectin levels compared with wild-type mice. Acute leptin injection revealed
      impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a
      high-fat diet (HFD) were significantly obese, presenting greater food intake and
      lower energy expenditure. HFD-fed KO mice were also characterized by greater
      impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease
      in food consumption compared with HFD-fed wild-type mice. In wild-type mice,
      acute exogenous leptin injection or chronic HFD feeding tended to induce
      hypothalamic Epac2a expression. CONCLUSIONS: Considering that HFD is an inducer
      of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta
      cells during demands of greater work load, hypothalamic Epac2a may have a role in
      facilitating leptin signaling, at least in response to higher metabolic demands.
      Thus, our data indicate that Epac2a is critical for preventing obesity and thus
      Epac2a activators may be used to manage obesity and obesity-mediated metabolic
      disorders.

PMID- 27867202
TI  - Generalization and fine mapping of European ancestry-based central adiposity
      variants in African ancestry populations.
AB  - BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference
      (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders
      independently of body mass index (BMI) and are gaining clinically utility.
      Several studies report genetic variants associated with central adiposity, but
      most utilize only European ancestry populations. Understanding whether the
      genetic associations discovered among mainly European descendants are shared with
      African ancestry populations will help elucidate the biological underpinnings of
      abdominal fat deposition. SUBJECTS/METHODS: To identify the underlying functional
      genetic determinants of body fat distribution, we conducted an array-wide
      association meta-analysis among persons of African ancestry across seven
      studies/consortia participating in the Population Architecture using Genomics and
      Epidemiology (PAGE) consortium. We used the Metabochip array, designed for fine
      mapping cardiovascular-associated loci, to explore novel array-wide associations
      with WC and WHR among 15 945 African descendants using all and sex-stratified
      groups. We further interrogated 17 known WHR regions for African ancestry
      specific variants. RESULTS: Of the 17 WHR loci, eight single-nucleotide
      polymorphisms (SNPs) located in four loci were replicated in the sex-combined or
      sex-stratified meta-analyses. Two of these eight independently associated with
      WHR after conditioning on the known variant in European descendants (rs12096179
      in TBX15-WARS2 and rs2059092 in ADAMTS9). In the fine-mapping assessment, the
      putative functional region was reduced across all four loci but to varying
      degrees (average 40% drop in number of putative SNPs and 20% drop in genomic
      region). Similar to previous studies, the significant SNPs in the female
      stratified analysis were stronger than the significant SNPs from the sex-combined
      analysis. No novel associations were detected in the array-wide analyses.
      CONCLUSIONS: Of 17 previously identified loci, four loci replicated in the
      African ancestry populations of this study. Utilizing different linkage
      disequilibrium patterns observed between European and African ancestries, we
      narrowed the suggestive region containing causative variants for all four loci.

PMID- 27867206
TI  - Structural Effects in the Recognition of DNA by Circular Oligonucleotides.
AB  - It was recently reported that certain pyrimidine-rich circular DNA oligomers can
      bind strongly and specifically to purine-rich DNA or RNA strands by forming
      bimolecular triple helical complexes.1-3 In this study are investigated the
      effects of structural variations on the strength of binding for this new class of
      nucleotide-binding ligand. The number of loop nucleotides (nt) which is optimum
      for bridging the two binding domains of a circle is examined. Comparing loop
      sizes of 3, 4, 5, 6, and 10 nt, the optimum number of nucleotides in a loop is
      found to be five for the sequences studied. In order to test the method of
      construction and the ability of these compounds to bind sites of varied length,
      we attempted to synthesize circles of varied size. Circles over the size range 24
      46 nt were successfully constructed. Varying the target site length shows that
      oligomers of four, eight, twelve, and eighteen nucleotides can be complexed
      strongly by circles, with melting temperatures (Tm) 17 degrees  to >33  degrees C
      higher at pH 7.0 than the corresponding Watson-Crick duplexes of the same length.
      Also studied is the effect of the covalently closed circular structure in
      comparison to linear oligomers having the same sequence; it is shown that a
      covalently closed circle has considerably higher binding affinity than do three
      different "nicked" circles (linear oligomers) which contain the same bases. The
      high binding affinities of these circles are thus attributed to the entropic
      benefit of preorganization. Finally, the ability of such circles to bind to
      complementary sites within longer oligomers, the ends of which must pass beyond
      the loops of a circle, is confirmed by melting studies with synthetic target
      strands 36 bases in length.

PMID- 27867204
TI  - A brief intervention for weight control based on habit-formation theory delivered
      through primary care: results from a randomised controlled trial.
AB  - BACKGROUND: Primary care is the 'first port of call' for weight control advice,
      creating a need for simple, effective interventions that can be delivered without
      specialist skills. Ten Top Tips (10TT) is a leaflet based on habit-formation
      theory that could fill this gap. The aim of the current study was to test the
      hypothesis that 10TT can achieve significantly greater weight loss over 3 months
      than 'usual care'. METHODS: A two-arm, individually randomised, controlled trial
      in primary care. Adults with obesity were identified from 14 primary care
      providers across England. Patients were randomised to either 10TT or 'usual care'
      and followed up at 3, 6, 12, 18 and 24 months. The primary outcome was weight
      loss at 3 months, assessed by a health professional blinded to group allocation.
      Difference between arms was assessed using a mixed-effect linear model taking
      into account the health professionals delivering 10TT, and adjusted for baseline
      weight. Secondary outcomes included body mass index, waist circumference, the
      number achieving a 5% weight reduction, clinical markers for potential
      comorbidities, weight loss over 24 months and basic costs. RESULTS: Five-hundred
      and thirty-seven participants were randomised to 10TT (n=267) or to 'usual care'
      (n=270). Data were available for 389 (72%) participants at 3 months and for 312
      (58%) at 24 months. Participants receiving 10TT lost significantly more weight
      over 3 months than those receiving usual care (mean difference =-0.87kg; 95%
      confidence interval: -1.47 to -0.27; P=0.004). At 24 months, the 10TT group had
      maintained their weight loss, but the 'usual care' group had lost a similar
      amount. The basic cost of 10TT was low, that is, around L23 ($32) per
      participant. CONCLUSIONS: The 10TT leaflet delivered through primary care is
      effective in the short-term and a low-cost option over the longer term. It is the
      first habit-based intervention to be used in a health service setting and offers
      a low-intensity alternative to 'usual care'.

PMID- 27867205
TI  - Interactive effects of obesity and physical fitness on risk of ischemic heart
      disease.
AB  - BACKGROUND/OBJECTIVES: Obesity and low physical fitness are known risk factors
      for ischemic heart disease (IHD), but their interactive effects are unclear.
      Elucidation of interactions between these common, modifiable risk factors may
      help inform more effective preventive strategies. We examined interactive effects
      of obesity, aerobic fitness and muscular strength in late adolescence on risk of
      IHD in adulthood in a large national cohort. SUBJECTS/METHODS: We conducted a
      national cohort study of all 1 547 407 military conscripts in Sweden during 1969
      1997 (97-98% of all 18-year-old males each year). Aerobic fitness, muscular
      strength and body mass index (BMI) measurements were examined in relation to IHD
      identified from outpatient and inpatient diagnoses through 2012 (maximum age 62
      years). RESULTS: There were 38 142 men diagnosed with IHD in 39.7 million person
      years of follow-up. High BMI or low aerobic fitness (but not muscular strength)
      was associated with higher risk of IHD, adjusting for family history and
      socioeconomic factors. The combination of high BMI (overweight/obese vs normal)
      and low aerobic fitness (lowest vs highest tertile) was associated with highest
      IHD risk (incidence rate ratio, 3.11; 95% confidence interval (CI), 2.91-3.31;
      P<0.001). These exposures had no additive and a negative multiplicative
      interaction (that is, their combined effect was less than the product of their
      separate effects). Low aerobic fitness was a strong risk factor even among those
      with normal BMI. CONCLUSIONS: In this large cohort study, low aerobic fitness or
      high BMI at age 18 was associated with higher risk of IHD in adulthood, with a
      negative multiplicative interaction. Low aerobic fitness appeared to account for
      a similar number of IHD cases among those with normal vs high BMI (that is, no
      additive interaction). These findings suggest that interventions to prevent IHD
      should begin early in life and include not only weight control but aerobic
      fitness, even among persons of normal weight.

PMID- 27867207
TI  - Purification of Bioactive Lipopeptides Produced by Bacillus subtilis Strain BIA.
AB  - Bacillus subtilis strain BIA was used for the production of bioactive
      lipopeptides. Different extraction and purification methods were assayed as
      liquid-liquid extraction, and acid and ammonium sulfate precipitation followed by
      TLC, SPE, and gel filtration. Active fractions were further purified using RP
      HPLC. The molecular mass of the purified product from HPLC was determined through
      Tris-Tricine SDS-PAGE and MALDI-TOF-MS. The results revealed that Bacillus
      subtilis strain BIA produced surfactin and iturin like compounds. Coproduction of
      surfactin and iturin like compounds by this strain is a remarkable trait for a
      potential biocontrol agent. This paper also includeds techniques that have been
      developed for the optimal and convenient extraction of bioactive lipopeptides
      from microbial origin.

PMID- 27867208
TI  - ANTIBIOTIC SUSCEPTIBILITY OF ORGANISMS CAUSING URINARY TRACT INFECTION IN
      PATIENTS PRESENTING AT KENYATTA NATIONAL HOSPITAL, NAIROBI.
AB  - BACKGROUND: Changes in susceptibility patterns of bacterial pathogens isolated
      from urinary tract infections emphasize the need for regional surveillance to
      generate information that can be used in management of patients. Knowledge on the
      current status of antimicrobial resistance in uropathogens, and the prevalence of
      expanding spectrum beta-lactamases (ESBLs) in the isolates will guide policy
      formulations and encourage prudent use of antimicrobials. OBJECTIVE: Identify
      bacterial pathogens causing UTI and determine the association between the
      pathogens isolated from patients attending KNH. Determine antimicrobial
      susceptibility patterns of the UTI pathogens and the prevalence of ESBL in the
      isolated pathogens. DESIGN: Laboratory-based study. SETTING: Department of
      Medical Microbiology University of Nairobi and Kenyatta National Hospital
      microbiology laboratory, Nairobi, Kenya. SUBJECTS: Nine hundred and forty eight
      patients presenting directly to the Kenyatta National Hospital's diagnostic lab.
      Patients were only classified as in-patients if at the time of specimen
      collection they were being admitted to one of KNH wards. RESULTS: Out of the 948
      urine samples processed, 189 in-patients and 37 out-patients samples had
      significant bacterial growth. The uropathogens identified from in-patient
      specimens were Escherichia coli (56), Klebsiellapneumoniae (33), Enterococcus
      spp. (34) and Entrobacter (16) making up 30%, 18%, 18% and 9% respectively. ESBL
      isolates were found to be resistant to the locally administered antibiotics;
      Augmentin (37%), Levofloxacin (37%), Cefoperazone (37%), Ampicillin (39%),
      Doxycyline (41%), Gentamicin (30%) and Nalidixic Acid (38%). CONCLUSION: The
      increased prevalence of multidrug resistant ESBL pathogens poses challenges for
      health care providers at KNH and signifies the need for new approach to treat
      UTI. It would be prudent for laboratories to include specialized tests for
      detection of ESBL producing pathogens from isolates obtained from in-patients.
      Further studies on the mechanisms and pathways utilized by these bacteria to
      cause UTI will highlight other avenues in patient management.

PMID- 27867209
TI  - Adsorption and desorption of arsenic to aquifer sediment on the Red River
      floodplain at Nam Du, Vietnam.
AB  - The adsorption of arsenic onto aquifer sediment from the Red River floodplain,
      Vietnam, was determined in a series of batch experiments. Due to water supply
      pumping, river water infiltrates into the aquifer at the field site and has
      leached the uppermost aquifer sediments. The leached sediments, remain anoxic but
      contain little reactive arsenic and iron, and are used in our experiments. The
      adsorption and desorption experiments were carried out by addition or removal of
      arsenic from the aqueous phase in sediment suspensions under strictly anoxic
      conditions. Also the effects of HCO3, Fe(II), PO4 and Si on arsenic adsorption
      were explored. The results show much stronger adsorption of As(V) as compared to
      As(III), full reversibility for As(III) adsorption and less so for As(V). The
      presence or absence of HCO3 did not influence arsenic adsorption. Fe(II) enhanced
      As(V) sorption but did not influence the adsorption of As(III) in any way. During
      simultaneous adsorption of As(III) and Fe(II), As(III) was found to be fully
      desorbable while Fe(II) was completely irreversibly adsorbed and clearly the two
      sorption processes are uncoupled. Phosphate was the only solute that
      significantly could displace As(III) from the sediment surface. Compiling
      literature data on arsenic adsorption to aquifer sediment in Vietnam and
      Bangladesh revealed As(III) isotherms to be almost identical regardless of the
      nature of the sediment or the site of sampling. In contrast, there was a large
      variation in As(V) adsorption isotherms between studies. A tentative conclusion
      is that As(III) and As(V) are not adsorbing onto the same sediment surface sites.
      The adsorption behavior of arsenic onto aquifer sediments and synthetic Fe-oxides
      is compared. Particularly, the much stronger adsorption of As(V) than of As(III)
      onto Red River as well as on most Bangladesh aquifer sediments, indicates that
      the perception that arsenic, phosphate and other species compete for the same
      surface sites of iron oxides in sediments with properties similar to those of,
      for example a synthetic goethite, probably is not correct. A simple two-component
      Langmuir adsorption model was constructed to quantitatively describe the reactive
      transport of As(III) and PO4 in the aquifer.

PMID- 27867210
TI  - A model for the evolution in water chemistry of an arsenic contaminated aquifer
      over the last 6000 years, Red River floodplain, Vietnam.
AB  - Aquifers on the Red River flood plain with burial ages ranging from 500 to 6000
      years show, with increasing age, the following changes in solute concentrations;
      a decrease in arsenic, increase in Fe(II) and decreases in both pH, Ca and
      bicarbonate. These changes were interpreted in terms of a reaction network
      comprising the kinetics of organic carbon degradation, the reduction kinetics of
      As containing Fe-oxides, the sorption of arsenic, the kinetics of siderite
      precipitation and dissolution, as well as of the dissolution of CaCO3. The
      arsenic released from the Fe-oxide is preferentially partitioned into the water
      phase, and partially sorbed, while the released Fe(II) is precipitated as
      siderite. The reaction network involved in arsenic mobilization was analyzed by 1
      D reactive transport modeling. The results reveal complex interactions between
      the kinetics of organic matter degradation and the kinetics and thermodynamic
      energy released by Fe-oxide reduction. The energy released by Fe-oxide reduction
      is strongly pH dependent and both methanogenesis and carbonate precipitation and
      dissolution have important influences on the pH. Overall it is the rate of
      organic carbon degradation that determines the total electron flow. However, the
      kinetics of Fe-oxide reduction determines the distribution of this flow of
      electrons between methanogenesis, which is by far the main pathway, and Fe-oxide
      reduction. Modeling the groundwater arsenic content over a 6000 year period in a
      20 m thick aquifer shows an increase in As during the first 1200 years where it
      reaches a maximum of about 600 MUg/L. During this initial period the release of
      arsenic from Fe-oxides actually decreases but the adsorption of arsenic onto the
      sediment delays the build-up in the groundwater arsenic concentration. After 1200
      years the groundwater arsenic content slowly decreases controlled both by
      desorption and continued further, but diminishing, release from Fe-oxide being
      reduced. After 6000 years the arsenic content has decreased to 33 MUg/L. The
      modeling enables a quantitative description of how the aquifer properties, the
      reactivity of organic carbon and Fe-oxides, the number of sorption sites and the
      buffering mechanisms change over a 6000 year period and how the combined effect
      of these interacting processes controls the groundwater arsenic content.

PMID- 27867211
TI  - Teaching tools to engage Anishinaabek First Nations women in cervical cancer
      screening: Report of an educational workshop.
AB  - OBJECTIVE: To explore educational strategies for engaging First Nations women in
      Canada to attend cervical cancer screening. DESIGN: Within a participatory action
      research framework, semi-structured interviews with health-care providers in
      First Nations communities revealed that education about the value of screening is
      perceived as being a key factor to promote cervical cancer screening. SETTING: To
      obtain feedback from workshop informants, a 1-day educational workshop was held
      to identify appropriate educational intervention strategies, which would be
      applied in a forthcoming randomised controlled cervical screening trial. METHODS:
      Common discussion and discussion groups, which were facilitated by a First
      Nations workshop moderator and a note taker. RESULTS: This workshop helped to
      strengthen the ethical space dialogue with the First Nations communities with
      whom the study team had established research partnerships. The workshop
      atmosphere was relaxed and the invited informants decided that an educational
      health promotion event for community women needed to be held prior to inviting
      them to the cervical screening trial. Such an event would provide an opportunity
      to communicate the importance of attending regular cervical screening allowing
      women to make informed decisions about screening participation. Complementary
      promotional items, including an eye-catching pamphlet and storytelling, were also
      suggested. CONCLUSION: The key messages from the events and promotional items can
      help to destigmatise women who develop a type of cancer that is caused by a
      sexually transmitted virus that affects both men and women. Developing and
      implementing positive health education that respectfully depicts female bodies,
      sexuality and health behaviours through a First Nations lens is strongly
      warranted.

PMID- 27867213
TI  - Screening for a Chronic Disease: A Multiple Stage Duration Model with Partial
      Observability.
AB  - We estimate a dynamic multi-stage duration model to investigate how early
      detection of diabetes can delay the onset of lower extremity complications and
      death. We allow for partial observability of the disease stage, unmeasured
      heterogeneity, and endogenous timing of diabetes screening. Timely diagnosis
      appears important. We evaluate the effectiveness of two potential policies to
      reduce the monetary costs of frequent screening in terms of lost longevity.
      Compared to the status quo, the more restrictive policy yields an implicit value
      for an additional year of life of about $50,000, while the less restrictive
      policy implies a value of about $120,000.

PMID- 27867212
TI  - Adaptive Angular Sampling for SPECT Imaging.
AB  - This paper presents an analytical approach for performing adaptive angular
      sampling in single photon emission computed tomography (SPECT) imaging. It allows
      for a rapid determination of the optimum sampling strategy that minimizes image
      variance in regions-of-interest (ROIs). The proposed method consists of three key
      components: (a) a set of close-form equations for evaluating image variance and
      resolution attainable with a given sampling strategy, (b) a gradient-based
      algorithm for searching through the parameter space to find the optimum sampling
      strategy and (c) an efficient computation approach for speeding up the search
      process. In this paper, we have demonstrated the use of the proposed analytical
      approach with a single-head SPECT system for finding the optimum distribution of
      imaging time across all possible sampling angles. Compared to the conventional
      uniform angular sampling approach, adaptive angular sampling allows the camera to
      spend larger fractions of imaging time at angles that are more efficient in
      acquiring useful imaging information. This leads to a significantly lowered image
      variance. In general, the analytical approach developed in this study could be
      used with many nuclear imaging systems (such as SPECT, PET and X-ray CT) equipped
      with adaptive hardware. This strategy could provide an optimized sampling
      efficiency and therefore an improved image quality.

PMID- 27867214
TI  - Immersive virtual reality in computational chemistry: Applications to the
      analysis of QM and MM data.
AB  - The role of Virtual Reality (VR) tools in molecular sciences is analyzed in this
      contribution through the presentation of the Caffeine software to the quantum
      chemistry community. Caffeine, developed at Scuola Normale Superiore, is
      specifically tailored for molecular representation and data visualization with VR
      systems, such as VR theaters and helmets. Usefulness and advantages that can be
      gained by exploiting VR are here reported, considering few examples specifically
      selected to illustrate different level of theory and molecular representation.

PMID- 27867215
TI  - Resolving large-scale pressures on species and ecosystems: propensity modelling
      identifies agricultural effects on streams.
AB  - Although agriculture is amongst the world's most widespread land uses, studies of
      its effects on stream ecosystems are often limited in spatial extent. National
      monitoring data could extend spatial coverage and increase statistical power, but
      present analytical challenges where covarying environmental variables confound
      relationships of interest.Propensity modelling is used widely outside ecology to
      control for confounding variables in observational data. Here, monitoring data
      from over 3000 English and Welsh river reaches are used to assess the effects of
      intensive agricultural land cover (arable and pastoral) on stream habitat, water
      chemistry and invertebrates, using propensity scores to control for potential
      confounding factors (e.g. climate, geology). Propensity scoring effectively
      reduced the collinearity between land cover and potential confounding variables,
      reducing the potential for covariate bias in estimated treatment-response
      relationships compared to conventional multiple regression.Macroinvertebrate
      richness was significantly greater at sites with a higher proportion of improved
      pasture in their catchment or riparian zone, with these effects probably mediated
      by increased algal production from mild nutrient enrichment. In contrast,
      macroinvertebrate richness did not change with arable land cover, although
      sensitive species representation was lower under higher proportions of arable
      land cover, probably due to greatly elevated nutrient concentrations. Synthesis
      and applications. Propensity modelling has great potential to address questions
      about pressures on ecosystems and organisms at the large spatial extents relevant
      to land-use policy, where experimental approaches are not feasible and broad
      environmental changes often covary. Applied to the effects of agricultural land
      cover on stream systems, this approach identified reduced nutrient loading from
      arable farms as a priority for land management. On this specific issue, our data
      and analysis support the use of riparian or catchment-scale measures to reduce
      nutrient delivery to sensitive water bodies.

PMID- 27867216
TI  - Investigating the impacts of field-realistic exposure to a neonicotinoid
      pesticide on bumblebee foraging, homing ability and colony growth.
AB  - The ability to forage and return home is essential to the success of bees as both
      foragers and pollinators. Pesticide exposure may cause behavioural changes that
      interfere with these processes, with consequences for colony persistence and
      delivery of pollination services.We investigated the impact of chronic exposure
      (5-43 days) to field-realistic levels of a neonicotinoid insecticide (2.4 ppb
      thiamethoxam) on foraging ability, homing success and colony size using radio
      frequency identification (RFID) technology in free-flying bumblebee
      colonies.Individual foragers from pesticide-exposed colonies carried out longer
      foraging bouts than untreated controls (68 vs. 55 min). Pesticide-exposed bees
      also brought back pollen less frequently than controls indicating reduced
      foraging performance.A higher proportion of bees from pesticide-exposed colonies
      returned when released 1 km from their nests; this is potentially related to
      increased orientation experience during longer foraging bouts. We measured no
      impact of pesticide exposure on homing ability for bees released from 2 km, or
      when data were analysed overall.Despite a trend for control colonies to produce
      more new workers earlier, we found no overall impacts of pesticide exposure on
      whole colony size. Synthesis and applications. This study shows that field
      realistic neonicotinoid exposure can have impacts on both foraging ability and
      homing success of bumblebees, with implications for the success of bumblebee
      colonies in agricultural landscapes and their ability to deliver crucial
      pollination services. Pesticide risk assessments should include bee species other
      than honeybees and assess a range of behaviours to elucidate the impact of
      sublethal effects. This has relevance for reviews of neonicotinoid risk
      assessment and usage policy world-wide.

PMID- 27867217
TI  - Avoidance of wind farms by harbour seals is limited to pile driving activities.
AB  - As part of global efforts to reduce dependence on carbon-based energy sources
      there has been a rapid increase in the installation of renewable energy devices.
      The installation and operation of these devices can result in conflicts with
      wildlife. In the marine environment, mammals may avoid wind farms that are under
      construction or operating. Such avoidance may lead to more time spent travelling
      or displacement from key habitats. A paucity of data on at-sea movements of
      marine mammals around wind farms limits our understanding of the nature of their
      potential impacts.Here, we present the results of a telemetry study on harbour
      seals Phoca vitulina in The Wash, south-east England, an area where wind farms
      are being constructed using impact pile driving. We investigated whether seals
      avoid wind farms during operation, construction in its entirety, or during piling
      activity. The study was carried out using historical telemetry data collected
      prior to any wind farm development and telemetry data collected in 2012 during
      the construction of one wind farm and the operation of another.Within an
      operational wind farm, there was a close-to-significant increase in seal usage
      compared to prior to wind farm development. However, the wind farm was at the
      edge of a large area of increased usage, so the presence of the wind farm was
      unlikely to be the cause.There was no significant displacement during
      construction as a whole. However, during piling, seal usage (abundance) was
      significantly reduced up to 25 km from the piling activity; within 25 km of the
      centre of the wind farm, there was a 19 to 83% (95% confidence intervals)
      decrease in usage compared to during breaks in piling, equating to a mean
      estimated displacement of 440 individuals. This amounts to significant
      displacement starting from predicted received levels of between 166 and 178 dB re
      1 MUPa(p-p). Displacement was limited to piling activity; within 2 h of cessation
      of pile driving, seals were distributed as per the non-piling scenario. Synthesis
      and applications. Our spatial and temporal quantification of avoidance of wind
      farms by harbour seals is critical to reduce uncertainty and increase robustness
      in environmental impact assessments of future developments. Specifically, the
      results will allow policymakers to produce industry guidance on the likelihood of
      displacement of seals in response to pile driving; the relationship between sound
      levels and avoidance rates; and the duration of any avoidance, thus allowing far
      more accurate environmental assessments to be carried out during the consenting
      process. Further, our results can be used to inform mitigation strategies in
      terms of both the sound levels likely to cause displacement and what temporal
      patterns of piling would minimize the magnitude of the energetic impacts of
      displacement.

PMID- 27867218
TI  - Predictive Validity of an Empirical Approach for Selecting Promising Message
      Topics: A Randomized-Controlled Study.
AB  - Several message topic selection approaches propose that messages based on beliefs
      pretested and found to be more strongly associated with intentions will be more
      effective in changing population intentions and behaviors when used in a
      campaign. This study aimed to validate the underlying causal assumption of these
      approaches which rely on cross-sectional belief-intention associations. We
      experimentally tested whether messages addressing promising themes as identified
      by the above criterion were more persuasive than messages addressing less
      promising themes. Contrary to expectations, all messages increased intentions.
      Interestingly, mediation analyses showed that while messages deemed promising
      affected intentions through changes in targeted promising beliefs, messages
      deemed less promising also achieved persuasion by influencing nontargeted
      promising beliefs. Implications for message topic selection are discussed.

PMID- 27867220
TI  - Unsafe at Any Age: Linking Childhood and Adolescent Maltreatment to Delinquency
      and Crime.

PMID- 27867219
TI  - Finite magnetic relaxation in x-space magnetic particle imaging: Comparison of
      measurements and ferrohydrodynamic models.
AB  - Magnetic Particle Imaging (MPI) is an emerging tomographic imaging technology
      that detects magnetic nanoparticle tracers by exploiting their non-linear
      magnetization properties. In order to predict the behavior of nanoparticles in an
      imager, it is possible to use a non-imaging MPI relaxometer or spectrometer to
      characterize the behavior of nanoparticles in a controlled setting. In this paper
      we explore the use of ferrohydrodynamic magnetization equations for predicting
      the response of particles in an MPI relaxometer. These include a magnetization
      equation developed by Shliomis (Sh) which has a constant relaxation time and a
      magnetization equation which uses a field-dependent relaxation time developed by
      Martsenyuk, Raikher and Shliomis (MRSh). We compare the predictions from these
      models with measurements and with the predictions based on the Langevin function
      that assumes instantaneous magnetization response of the nanoparticles. The
      results show good qualitative and quantitative agreement between the
      ferrohydrodynamic models and the measurements without the use of fitting
      parameters and provide further evidence of the potential of ferrohydrodynamic
      modeling in MPI.

PMID- 27867221
TI  - Molecular Recognition by Circular Oligonucleotides. Strong Binding of Single
      stranded DNA and RNA.
AB  - Pyrimidine-rich circular DNA oligonucleotides 1 and 2 display very high binding
      affinities for complementary DNA and RNA oligomers by forming bimolecular triple
      helical complexes.

PMID- 27867222
TI  - Strong between-site variation in New Caledonian crows' use of hook-tool-making
      materials.
AB  - Functional tool use requires the selection of appropriate raw materials. New
      Caledonian crows Corvus moneduloides are known for their extraordinary tool
      making behaviour, including the crafting of hooked stick tools from branched
      vegetation. We describe a surprisingly strong between-site difference in the
      plant materials used by wild crows to manufacture these tools: crows at one study
      site use branches of the non-native shrub Desmanthus virgatus, whereas only
      approximately 7 km away, birds apparently ignore this material in favour of the
      terminal twigs of an as-yet-unidentified tree species. Although it is likely that
      differences in local plant communities drive this striking pattern, it remains to
      be determined how and why crows develop such strong site-specific preferences for
      certain raw materials.

PMID- 27867223
TI  - Thermomechanical Formation-Structure-Property Relationships in Photopolymerized
      Copper-Catalyzed Azide-Alkyne (CuAAC) Networks.
AB  - Bulk photopolymerization of a library of synthesized multifunctional azides and
      alkynes was carried out toward developing structure-property relationships for
      CuAAC-based polymer networks. Multifunctional azides and alkynes were formulated
      with a copper catalyst and a photoinitiator, cured, and analyzed for their
      mechanical properties. Material properties such as the glass transition
      temperatures (Tg) show a strong dependence on monomer structure with Tg values
      ranging from 41 to 90  degrees C for the series of CuAAC monomers synthesized in
      this study. Compared to the triazoles, analogous thioether-based polymer networks
      exhibit a 45-49  degrees C lower Tg whereas analogous monomers composed of ethers
      in place of carbamates exhibit a 40  degrees C lower Tg. Here, the formation of
      the triazole moiety during the polymerization represents a critical component in
      dictating the material properties of the ultimate polymer network where material
      properties such as the rubbery modulus, cross-link density, and Tg all exhibit
      strong dependence on polymerization conversion, monomer composition, and
      structure postgelation.

PMID- 27867224
TI  - Approximating the Little Grothendieck Problem over the Orthogonal and Unitary
      Groups.
AB  - The little Grothendieck problem consists of maximizing Sigma ij Cijxixj for a
      positive semidef-inite matrix C, over binary variables xi ? {+/-1}. In this paper
      we focus on a natural generalization of this problem, the little Grothendieck
      problem over the orthogonal group. Given C ? R dn * dn a positive semidefinite
      matrix, the objective is to maximize [Formula: see text] restricting Oi to take
      values in the group of orthogonal matrices [Formula: see text], where Cij denotes
      the (ij)-th d * d block of C. We propose an approximation algorithm, which we
      refer to as Orthogonal-Cut, to solve the little Grothendieck problem over the
      group of orthogonal matrices [Formula: see text] and show a constant
      approximation ratio. Our method is based on semidefinite programming. For a given
      d >= 1, we show a constant approximation ratio of alphaR(d)2, where alphaR(d) is
      the expected average singular value of a d * d matrix with random Gaussian
      [Formula: see text] i.i.d. entries. For d = 1 we recover the known alphaR(1)2 =
      2/pi approximation guarantee for the classical little Grothendieck problem. Our
      algorithm and analysis naturally extends to the complex valued case also
      providing a constant approximation ratio for the analogous little Grothendieck
      problem over the Unitary Group [Formula: see text]. Orthogonal-Cut also serves as
      an approximation algorithm for several applications, including the Procrustes
      problem where it improves over the best previously known approximation ratio of
      [Formula: see text]. The little Grothendieck problem falls under the larger class
      of problems approximated by a recent algorithm proposed in the context of the non
      commutative Grothendieck inequality. Nonetheless, our approach is simpler and
      provides better approximation with matching integrality gaps. Finally, we also
      provide an improved approximation algorithm for the more general little
      Grothendieck problem over the orthogonal (or unitary) group with rank
      constraints, recovering, when d = 1, the sharp, known ratios.

PMID- 27867225
TI  - TOTAL SYNTHESES OF PANCRATISTATIN. A REVIEW.

PMID- 27867227
TI  - A Pattern-Based Definition of Urban Context Using Remote Sensing and GIS.
AB  - In Sub-Saharan Africa rapid urban growth combined with rising poverty is creating
      diverse urban environments, the nature of which are not adequately captured by a
      simple urban-rural dichotomy. This paper proposes an alternative classification
      scheme for urban mapping based on a gradient approach for the southern portion of
      the West African country of Ghana. Landsat Enhanced Thematic Mapper Plus (ETM+)
      and European Remote Sensing Satellite-2 (ERS-2) synthetic aperture radar (SAR)
      imagery are used to generate a pattern based definition of the urban context.
      Spectral mixture analysis (SMA) is used to classify a Landsat scene into Built,
      Vegetation and Other land covers. Landscape metrics are estimated for Built and
      Vegetation land covers for a 450 meter uniform grid covering the study area. A
      measure of texture is extracted from the SAR imagery and classified as Built/Non
      built. SMA based measures of Built and Vegetation fragmentation are combined with
      SAR texture based Built/Non-built maps through a decision tree classifier to
      generate a nine class urban context map capturing the transition from unsettled
      land at one end of the gradient to the compact urban core at the other end.
      Training and testing of the decision tree classifier was done using very high
      spatial resolution reference imagery from Google Earth. An overall classification
      agreement of 77% was determined for the nine-class urban context map, with user's
      accuracy (commission errors) being lower than producer's accuracy (omission
      errors). Nine urban contexts were classified and then compared with data from the
      2000 Census of Ghana. Results suggest that the urban classes appropriately
      differentiate areas along the urban gradient.

PMID- 27867226
TI  - Testing the Impact of Child Characteristics * Instruction Interactions on Third
      Graders' Reading Comprehension by Differentiating Literacy Instruction.
AB  - There is accumulating correlational evidence that the effect of specific types of
      reading instruction depends on children's initial language and literacy skills,
      called child characteristics * instruction (C*I) interactions. There is, however,
      no experimental evidence beyond first grade. This randomized control study
      examined whether C*I interactions might present an underlying and predictable
      mechanism for explaining individual differences in how students respond to third
      grade classroom literacy instruction. To this end, we designed and tested an
      instructional intervention (Individualizing Student Instruction [ISI]). Teachers
      (n = 33) and their students (n = 448) were randomly assigned to the ISI
      intervention or a vocabulary intervention, which was not individualized. Teachers
      in both conditions received professional development. Videotaped classroom
      observations conducted in the fall, winter, and spring documented the instruction
      that each student in the classroom received. Teachers in the ISI group were more
      likely to provide differentiated literacy instruction that considered C*I
      interactions than were the teachers in the vocabulary group. Students in the ISI
      intervention made greater gains on a standardized assessment of reading
      comprehension than did students in the vocabulary intervention. Results indicate
      that C*I interactions likely contribute to students' varying response to literacy
      instruction with regard to their reading comprehension achievement and that the
      association between students' profile of language and literacy skills and
      recommended instruction is nonlinear and dependent on a number of factors. Hence,
      dynamic and complex theories about classroom instruction and environment impacts
      on student learning appear to be warranted and should inform more effective
      literacy instruction in third grade.

PMID- 27867228
TI  - Simplexolides A-E and plakorfuran A, six butyrate derived polyketides from the
      marine sponge Plakortis simplex.
AB  - Six new polyketides, simplexolides A-E (1-5) and a furan ester, plakorfuran A
      (6), together with four known furanylidenic methyl esters (7-10) were isolated
      from the marine sponge Plakortis simplex. Compounds 1-5 feature a tetrahydrofuran
      ring opened seco-plakortone skeleton. These new structures, including relative
      configurations, were determined on the basis of extensive analysis of
      spectroscopic data. The absolute configurations of 1-6 were established by the
      modified Mosher's method, and the CD exciton chirality method. However,
      configurations of the remote stereocenters at C-8 in compounds 1-5 were not
      determined. Antifungal, cytotoxicity, antileismanial, and antimalarial activities
      of these poly-ketides were evaluated.

PMID- 27867229
TI  - Eucalyptals D and E, new cytotoxic phloroglucinols from the fruits of Eucalyptus
      globulus and assignment of absolute configuration.
AB  - Two new phloroglucinols, named eucalyptals D (1) and E (2), along with a related
      known compound (euglobal-In-3, 3) were isolated from the fruits of Eucalyptus
      globulus. Their structures were established on the basis of extensive
      spectroscopic studies, revealing that they share a common 3,5-diformyl-isopentyl
      phloroglucinol unit, but each is instead coupled to a different sesquiterpenoid
      skeleton (aromadendrene in 1, cadinene in 2, and a spirosesquiterpene in 3).
      Compound 1 possessed an unusual seven-membered D ring with an ether bridge
      between C-2 of the aromadendrene moiety and C-2' of the aromatic unit. The
      absolute configuration of the isolates was defined by the comparison of
      experimental and calculated electronic circular dichroism (ECD) spectra.
      Compounds 1-3 exhibited significant in vitro cytotoxicities against a few human
      cancer cell lines (Huh-7, Jurkat, BGC-823, and KE-97) using the CellTiter-GloTM
      luminescent cell viability assay method.

PMID- 27867230
TI  - Isospora scinci (Apicomplexa: Eimeriidae) from Five-Lined Skinks, Plestiodon
      fasciatus (Sauria: Scincidae): Additional Records from Arkansas and First Report
      from Oklahoma.

PMID- 27867231
TI  - Interviewing Practices, Conversational Practices, and Rapport: Responsiveness and
      Engagement in the Standardized Survey Interview.
AB  - "Rapport" has been used to refer to a range of positive psychological features of
      an interaction -- including a situated sense of connection or affiliation between
      interactional partners, comfort, willingness to disclose or share sensitive
      information, motivation to please, or empathy. Rapport could potentially benefit
      survey participation and response quality by increasing respondents' motivation
      to participate, disclose, or provide accurate information. Rapport could also
      harm data quality if motivation to ingratiate or affiliate caused respondents to
      suppress undesirable information. Some previous research suggests that motives
      elicited when rapport is high conflict with the goals of standardized
      interviewing. We examine rapport as an interactional phenomenon, attending to
      both the content and structure of talk. Using questions about end-of-life
      planning in the 2003-2005 wave of the Wisconsin Longitudinal Study, we observe
      that rapport consists of behaviors that can be characterized as dimensions of
      responsiveness by interviewers and engagement by respondents. We identify and
      describe types of responsiveness and engagement in selected question-answer
      sequences and then devise a coding scheme to examine their analytic potential
      with respect to the criterion of future study participation. Our analysis
      suggests that responsive and engaged behaviors vary with respect to the goals of
      standardization-some conflict with these goals, while others complement them.

PMID- 27867232
TI  - Professional boundaries and the identity of counselling psychology in South
      Africa.

PMID- 27867233
TI  - Influence of anthropogenic aerosol deposition on the relationship between oceanic
      productivity and warming.
AB  - Satellite data and models suggest that oceanic productivity is reduced in
      response to less nutrient supply under warming. In contrast, anthropogenic
      aerosols provide nutrients and exert a fertilizing effect, but its contribution
      to evolution of oceanic productivity is unknown. We simulate the response of
      oceanic biogeochemistry to anthropogenic aerosols deposition under varying
      climate from 1850 to 2010. We find a positive response of observed chlorophyll to
      deposition of anthropogenic aerosols. Our results suggest that anthropogenic
      aerosols reduce the sensitivity of oceanic productivity to warming from -15.2 +/-
      1.8 to -13.3 +/- 1.6 Pg C yr-1  degrees C-1 in global stratified oceans during
      1948-2007. The reducing percentage over the North Atlantic, North Pacific, and
      Indian Oceans reaches 40, 24, and 25%, respectively. We hypothesize that
      inevitable reduction of aerosol emissions in response to higher air quality
      standards in the future might accelerate the decline of oceanic productivity per
      unit warming.

PMID- 27867234
TI  - Revisiting the hemispheric asymmetry in midlatitude ozone changes following the
      Mount Pinatubo eruption: A 3-D model study.
AB  - Following the eruption of Mount Pinatubo, satellite and in situ measurements
      showed a large enhancement in stratospheric aerosol in both hemispheres, but
      significant midlatitude column O3 depletion was observed only in the north. We
      use a three-dimensional chemical transport model to determine the mechanisms
      behind this hemispheric asymmetry. The model, forced by European Centre for
      Medium-Range Weather Forecasts ERA-Interim reanalyses and updated aerosol surface
      area density, successfully simulates observed large column NO2 decreases and the
      different extents of ozone depletion in the two hemispheres. The chemical ozone
      loss is similar in the Northern (NH) and Southern Hemispheres (SH), but the
      contrasting role of dynamics increases the depletion in the NH and decreases it
      in the SH. The relevant SH dynamics are not captured as well by earlier ERA-40
      reanalyses. Overall, the smaller SH column O3 depletion can be attributed to
      dynamical variability and smaller SH background lower stratosphere O3
      concentrations.

PMID- 27867235
TI  - Transient, small-scale field-aligned currents in the plasma sheet boundary layer
      during storm time substorms.
AB  - We report on field-aligned current observations by the four Magnetospheric
      Multiscale (MMS) spacecraft near the plasma sheet boundary layer (PSBL) during
      two major substorms on 23 June 2015. Small-scale field-aligned currents were
      found embedded in fluctuating PSBL flux tubes near the separatrix region. We
      resolve, for the first time, short-lived earthward (downward) intense field
      aligned current sheets with thicknesses of a few tens of kilometers, which are
      well below the ion scale, on flux tubes moving equatorward/earthward during
      outward plasma sheet expansion. They coincide with upward field-aligned electron
      beams with energies of a few hundred eV. These electrons are most likely due to
      acceleration associated with a reconnection jet or high-energy ion beam-produced
      disturbances. The observations highlight coupling of multiscale processes in PSBL
      as a consequence of magnetotail reconnection.

PMID- 27867236
TI  - Direct observation of the thermal demagnetization of magnetic vortex structures
      in nonideal magnetite recorders.
AB  - The thermal demagnetization of pseudo-single-domain (PSD) magnetite (Fe3O4)
      particles, which govern the magnetic signal in many igneous rocks, is examined
      using off-axis electron holography. Visualization of a vortex structure held by
      an individual Fe3O4 particle (~250 nm in diameter) during in situ heating is
      achieved through the construction and examination of magnetic-induction maps.
      Stepwise demagnetization of the remanence-induced Fe3O4 particle upon heating to
      above the Curie temperature, performed in a similar fashion to bulk thermal
      demagnetization measurements, revealed that its vortex state remains stable under
      heating close to its unblocking temperature and is recovered upon cooling with
      the same or reversed vorticity. Hence, the PSD Fe3O4 particle exhibits
      thermomagnetic behavior comparable to a single-domain carrier, and thus, vortex
      states are considered reliable magnetic recorders for paleomagnetic
      investigations.

PMID- 27867238
TI  - Comment: Addressing the Need for Portability in Big Data Model Building and
      Calibration.

PMID- 27867237
TI  - Facets of Arctic energy accumulation based on observations and reanalyses 2000
      2015.
AB  - Various observation- and reanalysis-based estimates of sea ice mass and ocean
      heat content trends imply that the energy imbalance of the Arctic climate system
      was similar [1.0 (0.9,1.2) Wm-2] to the global ocean average during the 2000-2015
      period. Most of this extra heat warmed the ocean, and a comparatively small
      fraction went into sea ice melt. Poleward energy transports and radiation
      contributed to this energy increase at varying strengths. On a seasonal scale,
      stronger radiative energy input during summer associated with the ice-albedo
      feedback enhances seasonal oceanic heat uptake and sea ice melt. In return, lower
      sea ice extent and higher sea surface temperatures lead to enhanced heat release
      from the ocean during fall. This weakens meridional temperature gradients,
      consequently reducing atmospheric energy transports into the polar cap. The
      seasonal cycle of the Arctic energy budget is thus amplified, whereas the
      Arctic's long-term energy imbalance is close to the global mean.

PMID- 27867239
TI  - Legal Status and Health Care: Mexican-Origin Children in California, 2001-2014.
AB  - Using restricted data from the 2001-2014 California Health Interview Surveys,
      this research illuminates the role of legal status in health care among Mexican
      origin children. The first objective is to provide a population-level overview of
      trends in health care access and utilization, along with the legal statuses of
      parents and children. The second objective is to examine the nature of
      associations between children's health care and legal status over time. We
      identify specific status-based distinctions that matter and investigate how their
      importance is changing. Despite the continuing significance of child nativity for
      health care, the descriptive analysis shows that the proportion of Mexican-origin
      children who are foreign born is declining. This trend suggests a potentially
      greater role of parental legal status in children's health care. Logistic
      regression analyses demonstrate that the importance of parental legal status
      varies with the health care indicator examined and the inclusion of child
      nativity in models. Moreover, variation in some aspects of children's health care
      coalesced more around parents' citizenship than documentation status in the past.
      With one exception, the salience of such distinctions has dissipated over time.

PMID- 27867240
TI  - Internal and International Migration Across the Urban Hierarchy in Albania.
AB  - The interactions between the processes of urbanization and international
      migration in less developed and transition countries have important repercussions
      for socioeconomic development, but are not well understood. Based on the
      retrospective data from the Albanian Living Standards Measurement Survey 2008, we
      first assess the geography of migration in terms of the rural-urban continuum,
      the urban hierarchy and the outside world since 1990. We then investigate the
      spatio-temporal diffusion of rural-to-urban and international movements using
      survival models. Results reveal an immediate onset of large-scale rural exodus,
      despite the post-communist crisis. Internal migrants mainly moved to the capital,
      bypassing secondary cities, and were predominantly female. Initially,
      international migrants were primarily men who tended to originate from the main
      urban agglomerations. The diffusion of opportunities to emigrate down the urban
      hierarchy and across the sexes then redirected the rural exodus abroad, despite
      domestic economic development. This evolution in population mobility is related
      to the gendered patterns and interlinkages of the two flows, as well as to rising
      inequalities within the urban hierarchy.

PMID- 27867241
TI  - Family Profiles and Educational Attainment.
AB  - The educational attainment of participants in the Chicago Longitudinal Study (93%
      Black and 7% Hispanic) was examined. Cluster analysis on measures of human
      capital resources, family dynamics and demographics was used to identify four
      distinct profiles of families. In general, children who had family profiles
      characterized by higher levels of human capital resources and more favorable
      scores on indictors of family functioning were more likely than other children to
      have higher educational attainment. Moreover, children who experienced a positive
      change in family profile characteristics between the ages of 8 and 12 were more
      likely than other children to have higher educational attainment. Implications
      for intervention and research are discussed.

PMID- 27867242
TI  - Childhood Predictors of Adult Substance Abuse.
AB  - Identification of the early determinants of substance abuse is a major focus of
      life course research. In this study, we investigated the child, family, and
      school-related antecedents of the onset and prevalence of substance abuse by age
      26 for a cohort of 1,208 low-income minority children in the Chicago Longitudinal
      Study. Data onon well-being have been collected prospectively since birth from
      administrative records, parents, teachers, and children. Results indicated that
      the prevalence of substance abuse by age 26 was 32 percent (self reports or
      criminal justice system records) with a median age of first use of 17. Probit
      regression analysis indicated that substance abuse prevalence was primarily
      determined by gender (males had a higher rate), trouble making behavior by age
      12, school mobility, and previous substance use. Family and peer predictors
      included involvement in the child welfare system by age 9, parent expectations
      for school success at age 9, parent substance abuse by children's age 15, and
      deviant peer affiliation by age 16. Age of first substance use was predicted by
      gender and race/ethnicity (males and Blacks had earlier incidence), involvement
      in the child welfare system, and family risk status at age 8. As with prevalence,
      the pattern of predictors for males was similar to the overall sample but the
      magnitude of effects was stronger.. The predictors of the timing of substance use
      dependency were gender, family conflict by age 5, involvement in the child
      welfare system, social maturity at age 9, adolescent school mobility, and school
      dropout by age 16. Findings indicate that the promotion of family involvement and
      positive school and social behavior can reduce the risk of substance abuse.

PMID- 27867243
TI  - Maltreatment prevention through early childhood intervention: A confirmatory
      evaluation of the Chicago Child-Parent Center preschool program.
AB  - Increased recognition of the consequences associated with child maltreatment has
      led to greater emphasis on its prevention. Promising maltreatment prevention
      strategies have been identified, but research continues to suffer from
      methodological limitations and a narrow focus on select prevention models. This
      investigation uses data from the Chicago Longitudinal Study to examine mediating
      mechanisms that link the Chicago Child-Parent Center preschool program to a
      reduction in overall child maltreatment and, more specifically, child neglect. We
      use structural equation modeling to test child, family, and school measures
      hypothesized to mediate the effects of CPC participation on maltreatment and
      neglect. Results indicate that a substantial proportion of the program's impacts
      can be accounted for by family support processes, including increased parent
      involvement in school and maternal educational attainment as well as decreased
      family problems. The CPC program's association with reduced school mobility and
      increased attendance in higher-quality schools also significantly mediated its
      effects on maltreatment and neglect. Further, a decrease in troublemaking
      behavior contributed modestly to mediating the program's association with
      maltreatment but not neglect. We discuss the implications of these results for
      the field of maltreatment prevention.

PMID- 27867244
TI  - Community-based organisations for vulnerable children in South Africa: Reach,
      psychosocial correlates, and potential mechanisms.
AB  - Community-based organisations (CBOs) have the potential to provide high quality
      services for orphaned and vulnerable children in resource-limited settings.
      However, evidence is lacking as to whether CBOs are reaching those who are most
      vulnerable, whether attending these organisations is associated with greater
      psychosocial wellbeing, and how they might work. This study addressed these three
      questions using cross-sectional data from 1848 South African children aged 9-13.
      Data were obtained from the Young Carers and Child Community Care studies, which
      both investigated child wellbeing in South Africa using standardised self-report
      measures. Children from the Child Community Care study were all CBO attenders,
      whereas children from Young Carers were not receiving any CBO services, thereby
      serving as a comparison group. Multivariable regression analyses were used to
      test whether children attending CBOs were more deprived on socio-demographic
      variables (e.g., housing), and whether CBO attendance was in turn associated with
      better psychosocial outcomes (e.g., child depression). Mediation analysis was
      conducted to test whether more positive home environments mediated the
      association between CBO attendance and significantly higher psychological
      wellbeing. Overall, children attending CBOs did show greater vulnerability on
      most socio-demographic variables. For example, compared to children not attending
      any CBO, CBO-attending children tended to live in more crowded households (OR
      1.22) and have been exposed to more community violence (OR 2.06). Despite their
      heightened vulnerability, however, children attending CBOs tended to perform
      better on psychosocial measures: for instance, showing fewer depressive symptoms
      (B=-0.33) and lower odds of experiencing physical (OR 0.07) or emotional abuse
      (OR 0.22). Indirect effects of CBO attendance on significantly higher child
      psychological wellbeing (lower depressive symptoms) was observed via lower rates
      of child abuse (B=-0.07) and domestic conflict/violence (B=-0.03) and higher
      rates of parental praise (B=-0.03). Null associations were observed between CBO
      attendance and severe psychopathology (e.g., suicidality). These cross-sectional
      results provide promising evidence regarding the potential success of CBO reach
      and impact but also highlight areas for improvement.

PMID- 27867245
TI  - Diamond coated artificial cardiovascular devices.
AB  - Ultrananocrystalline diamond (UNCD), an extremely smooth, low cost diamond
      coating was successfully developed herein for antithrombogenic application which
      requires high biocompatibility, low wear, low friction, and chemical inertness.
      The substrate materials utilized in the Jarvik 2000 ventricular assist device
      (VAD), silicon carbide and titanium alloy, provide an excellent substrate match
      for UNCD integration. The paper addresses the development of medical-quality UNCD
      films to significantly improve the knowledge base regarding the defect mechanisms
      of UNCD films, to reduce or eliminate known wear-inducing imperfections in the
      film, and to thoroughly characterize and test the films as well as assembled UNCD
      coated VADs. After the defect reduction and seeding experiments to improve film
      adhesion and coating quality, the best candidate deposition method has been down
      selected for coating and assembly of VAD parts from Jarvik Heart. The coated and
      assembled devices have been tested with mechanical and blood-simulating fluid
      hydrodynamic testing at Jarvik Heart for full verification of the new coating
      technology. UNCD interface takes advantage of combining unmatched durability and
      antithrombogenicity.

PMID- 27867246
TI  - Predicting stability and change in loneliness in later life.
AB  - This study examined potential discriminators of groups of older adults showing
      different patterns of stability or change in loneliness over 5 years: those who
      became lonely, overcame loneliness, were persistently lonely, and were
      persistently not lonely. Discriminant function analysis results showed that the
      persistently lonely, compared with the persistently not lonely, were more often
      living alone, widowed, and experiencing poorer health and perceived control.
      Moreover, changes in living arrangements and perceived control predicted
      loneliness change. In conclusion, perceiving that one is able to meet social
      needs is a predictor of loneliness and loneliness change and appears to be more
      important than people's friendships. Because the predictors were better able to
      predict entry into loneliness, results point to the promise of prevention
      approaches to loneliness interventions.

PMID- 27867247
TI  - "Extra Oomph:" Addressing Housing Disparities through Medical Legal Partnership
      Interventions.
AB  - Low-income households face common and chronic housing problems that have known
      health risks and legal remedies. The Medical Legal Partnership (MLP) program
      presents a unique opportunity to address housing problems and improve patient
      health through legal assistance offered in clinical settings. Drawn from in-depth
      interviews with 72 patients, this study investigated the outcomes of MLP
      interventions and compares results to similarly disadvantaged participants with
      no access to MLP services. Results indicate that participants in the MLP group
      were more likely to achieve adequate, affordable and stable housing than those in
      the comparison group. Study findings suggest that providing access to legal
      services in the healthcare setting can effectively address widespread health
      disparities rooted in problematic housing. Implications for policy and
      scalability are discussed with the conclusion that MLPs can shift professionals'
      consciousness as they work to improve housing and health trajectories for
      indigent groups using legal approaches.

PMID- 27867248
TI  - Comparability of Spot Versus Band Electrodes for Impedance Cardiography.
AB  - Although band and spot electrodes have been compared in prior research, they have
      not been evaluated (a) at identical anatomical locations, (b) during a single
      laboratory session, (c) with measures taken in close temporal proximity, (d)
      using a single impedance cardiograph unit, or (e) using sufficiently powerful
      statistical tests. Thirty-one healthy young adults completed a
      psychophysiological assessment which consisted of baseline, mental arithmetic
      stressor, and recovery conditions. Data from spot and band electrodes were
      collected by alternating between electrode types every minute of the experiment.
      Correlations between spot and band electrodes at absolute levels of all
      cardiovascular measures (cardiac output, impedance derivative, basal impedance
      level, Heather index, heart rate, left ventricular ejection time, pre-ejection
      period, stroke volume) were of high magnitude (ravg = .78), while the
      correlations for difference scores were lower (ravg = .50). Analyses of mean
      levels indicated spot electrodes yielded significantly lower values for the
      impedance derivative, Heather index, and basal impedance, and higher values for
      cardiac output and stroke volume, than band electrodes. The advantages and
      disadvantages associated with spot and band electrode configurations, as well as
      their use in ambulatory recording, are discussed.

PMID- 27867250
TI  - Approaches to the Estimation of the Local Average Treatment Effect in a
      Regression Discontinuity Design.
AB  - Regression discontinuity designs (RD designs) are used as a method for causal
      inference from observational data, where the decision to apply an intervention is
      made according to a 'decision rule' that is linked to some continuous variable.
      Such designs are being increasingly developed in medicine. The local average
      treatment effect (LATE) has been established as an estimator of the intervention
      effect in an RD design, particularly where a design's 'decision rule' is not
      adhered to strictly. Estimating the variance of the LATE is not necessarily
      straightforward. We consider three approaches to the estimation of the LATE: two
      stage least squares, likelihood-based and a Bayesian approach. We compare these
      under a variety of simulated RD designs and a real example concerning the
      prescription of statins based on cardiovascular disease risk score.

PMID- 27867249
TI  - Elevated Omentin Serum Levels Predict Long-Term Survival in Critically Ill
      Patients.
AB  - Introduction. Omentin, a recently described adipokine, was shown to be involved
      in the pathophysiology of inflammatory and infectious diseases. However, its role
      in critical illness and sepsis is currently unknown. Materials and Methods.
      Omentin serum concentrations were measured in 117 ICU-patients (84 with septic
      and 33 with nonseptic disease etiology) admitted to the medical ICU. Results were
      compared with 50 healthy controls. Results. Omentin serum levels of critically
      ill patients at admission to the ICU or after 72 hours of ICU treatment were
      similar compared to healthy controls. Moreover, circulating omentin levels were
      independent of sepsis and etiology of critical illness. Notably, serum
      concentrations of omentin could not be linked to concentrations of inflammatory
      cytokines or routinely used sepsis markers. While serum levels of omentin were
      not predictive for short term survival during ICU treatment, low omentin
      concentrations were an independent predictor of patients' overall survival.
      Omentin levels strongly correlated with that of other adipokines (e.g., leptin
      receptor or adiponectin), which have also been identified as prognostic markers
      in critical illness. Conclusions. Although circulating omentin levels did not
      differ between ICU-patients and controls, elevated omentin levels were predictive
      for an impaired patients' long term survival.

PMID- 27867251
TI  - Linear Increments with Non-monotone Missing Data and Measurement Error.
AB  - Linear increments (LI) are used to analyse repeated outcome data with missing
      values. Previously, two LI methods have been proposed, one allowing non-monotone
      missingness but not independent measurement error and one allowing independent
      measurement error but only monotone missingness. In both, it was suggested that
      the expected increment could depend on current outcome. We show that LI can allow
      non-monotone missingness and either independent measurement error of unknown
      variance or dependence of expected increment on current outcome but not both. A
      popular alternative to LI is a multivariate normal model ignoring the missingness
      pattern. This gives consistent estimation when data are normally distributed and
      missing at random (MAR). We clarify the relation between MAR and the assumptions
      of LI and show that for continuous outcomes multivariate normal estimators are
      also consistent under (non-MAR and non-normal) assumptions not much stronger than
      those of LI. Moreover, when missingness is non-monotone, they are typically more
      efficient.

PMID- 27867252
TI  - Sample Heterogeneity and the Measurement Structure of the Multidimensional
      Students' Life Satisfaction Scale.
AB  - Several measurement assumptions were examined with the goal of assessing the
      validity of the Multidimensional Students' Life Satisfaction Scale (MSLSS), a
      measure of adolescents' satisfaction with their family, friends, living
      environment, school, self, and general quality of life. The data were obtained
      via a cross-sectional survey of 8,225 adolescents in British Columbia, Canada.
      Confirmatory factor and factor mixture analyses of ordinal data were used to
      examine the measurement assumptions. The adolescents did not respond to all the
      MSLSS items in a psychometrically equivalent manner. A correlated five-factor
      model for an abridged version of the MSLSS resulted in good fit when all
      negatively worded items and several positively worded items (the least invariant)
      were excluded. The abridged 18-item version of the MSLSS provides a promising
      alternative for the measurement of five life domains that are pertinent to
      adolescents' quality of life.

PMID- 27867253
TI  - Drosophila ezoana uses an hour-glass or highly damped circadian clock for
      measuring night length and inducing diapause.
AB  - Insects inhabiting the temperate zones measure seasonal changes in day or night
      length to enter the overwintering diapause. Diapause induction occurs after the
      duration of the night exceeds a critical night length (CNL). Our understanding of
      the time measurement mechanisms is continuously evolving subsequent to Bunning's
      proposal that circadian systems play the clock role in photoperiodic time
      measurement (Bunning, 1936). Initially, the photoperiodic clocks were considered
      to be either based on circadian oscillators or on simple hour-glasses, depending
      on 'positive' or 'negative' responses in Nanda-Hamner and Bunsow experiments
      (Nanda & Hammer, 1958; Bunsow, 1960). However, there are also species whose
      responses can be regarded as neither 'positive', nor as 'negative', such as the
      Northern Drosophila species Drosophila ezoana, which is investigated in the
      present study. In addition, modelling efforts show that the 'positive' and
      'negative' Nanda-Hamner responses can also be provoked by circadian oscillators
      that are damped to different degrees: animals with highly sustained circadian
      clocks will respond 'positive' and those with heavily damped circadian clocks
      will respond 'negative'. In the present study, an experimental assay is proposed
      that characterizes the photoperiodic oscillators by determining the effects of
      non-24-h light/dark cycles (T-cycles) on critical night length. It is predicted
      that there is (i) a change in the critical night length as a function of T-cycle
      period in sustained-oscillator-based clocks and (ii) a fixed night-length
      measurement (i.e. no change in critical night length) in damped-oscillator-based
      clocks. Drosophila ezoana flies show a critical night length of approximately 7 h
      irrespective of T-cycle period, suggesting a damped-oscillator-based
      photoperiodic clock. The conclusion is strengthened by activity recordings
      revealing that the activity rhythm of D. ezoana flies also dampens in constant
      darkness.

PMID- 27867254
TI  - Network sampling coverage II: The effect of non-random missing data on network
      measurement.
AB  - Missing data is an important, but often ignored, aspect of a network study.
      Measurement validity is affected by missing data, but the level of bias can be
      difficult to gauge. Here, we describe the effect of missing data on network
      measurement across widely different circumstances. In Part I of this study (Smith
      and Moody, 2013), we explored the effect of measurement bias due to randomly
      missing nodes. Here, we drop the assumption that data are missing at random: what
      happens to estimates of key network statistics when central nodes are more/less
      likely to be missing? We answer this question using a wide range of empirical
      networks and network measures. We find that bias is worse when more central nodes
      are missing. With respect to network measures, Bonacich centrality is highly
      sensitive to the loss of central nodes, while closeness centrality is not;
      distance and bicomponent size are more affected than triad summary measures and
      behavioral homophily is more robust than degree-homophily. With respect to types
      of networks, larger, directed networks tend to be more robust, but the relation
      is weak. We end the paper with a practical application, showing how researchers
      can use our results (translated into a publically available java application) to
      gauge the bias in their own data.

PMID- 27867255
TI  - Bone Formation in Maxillary Sinus Lift Using Autogenous Bone Graft at 2 and 6
      Months.
AB  - The aim of this study is to compare the bone formation in maxillary sinus lift
      with an autogenous bone graft in histological evaluation at 2 or 6 months. A
      comparative study was designed where 10 patients with missing teeth bilaterally
      in the posterior zone of the maxilla were selected. Patients received a
      particulate autogenous bone graft under the same surgical conditions, selecting a
      site to collect a biopsy and histological study at two months and another at six
      months postoperatively. Histomorphometry was performed and were used Kolmogorov
      Smirnov test, student's t-test and Spearman's correlation coefficient,
      considering a value of p<0.05. Differences were observed in inflammatory
      infiltrate and vascularization characteristics; however, the group analyzed at
      two months presented 38.12% +/- 6.64 % of mineralized tissue, whereas the group
      studied at 6 months presented an average of 38.45 +/- 9.27 %. There were no
      statistical differences between the groups. It is concluded that the bone
      formation may be similar in intrasinus particulate autogenous bone grafts in
      evaluations at two or six months; under these conditions, early installation of
      implants is viable.

PMID- 27867256
TI  - Modular Polymer Biosensors by Solvent Immersion Imprint Lithography.
AB  - We recently demonstrated Solvent Immersion Imprint Lithography (SIIL), a rapid
      benchtop microsystem prototyping technique, including polymer functionalization,
      imprinting and bonding. Here, we focus on the realization of planar polymer
      sensors using SIIL through simple solvent immersion without imprinting. We
      describe SIIL's impregnation characteristics, including an inherent mechanism
      that not only achieves practical doping concentrations, but their unexpected 2
      fold enhancement compared to the immersion solution. Subsequently, we developed
      and characterized optical sensors for detecting molecular O2. To this end, a
      substantially high dynamic range is reported, including its control through the
      immersion duration, a manifestation of SIIL's modularity. Overall, SIIL exhibits
      the potential of improving the operating characteristics of polymer sensors,
      while significantly accelerating their prototyping, as it requires a few seconds
      of processing and no need for substrates or dedicated instrumentation. These are
      critical for O2 sensing as probed by way of example here, as well as any polymer
      permeable reactant.

PMID- 27867257
TI  - LearningRx Cognitive Training Effects in Children Ages 8-14: A Randomized
      Controlled Trial.
AB  - In a randomized controlled study, we examined the effects of a one-on-one
      cognitive training program on memory, visual and auditory processing, processing
      speed, reasoning, attention, and General Intellectual Ability (GIA) score for
      students ages 8-14. Participants were randomly assigned to either an experimental
      group to complete 60 h of cognitive training or to a wait-list control group. The
      purpose of the study was to examine changes in multiple cognitive skills after
      completing cognitive training with ThinkRx, a LearningRx program. Results showed
      statistically significant differences between groups on all outcome measures
      except for attention. Implications, limitations, and suggestions for future
      research are examined.

PMID- 27867258
TI  - Principle of Care and Giving to Help People in Need.
AB  - Theories of moral development posit that an internalized moral value that one
      should help those in need-the principle of care-evokes helping behaviour in
      situations where empathic concern does not. Examples of such situations are
      helping behaviours that involve cognitive deliberation and planning, that benefit
      others who are known only in the abstract, and who are out-group members.
      Charitable giving to help people in need is an important helping behaviour that
      has these characteristics. Therefore we hypothesized that the principle of care
      would be positively associated with charitable giving to help people in need, and
      that the principle of care would mediate the empathic concern-giving
      relationship. The two hypotheses were tested across four studies. The studies
      used four different samples, including three nationally representative samples
      from the American and Dutch populations, and included both self-reports of giving
      (Studies 1-3), giving observed in a survey experiment (Study 3), and giving
      observed in a laboratory experiment (Study 4). The evidence from these studies
      indicated that a moral principle to care for others was associated with
      charitable giving to help people in need and mediated the empathic concern-giving
      relationship. (c) 2016 The Authors. European Journal of Personality published by
      John Wiley & Sons Ltd on behalf of European Association of Personality
      Psychology.

PMID- 27867259
TI  - Personality and Other Lifelong Influences on Older-Age Health and Wellbeing:
      Preliminary Findings in Two Scottish Samples.
AB  - Recent observations that personality traits are related to later-life health and
      wellbeing have inspired considerable interest in exploring the mechanisms
      involved. Other factors, such as cognitive ability and education, also show
      longitudinal influences on health and wellbeing, but it is not yet clear how all
      these early-life factors together contribute to later-life health and wellbeing.
      In this preliminary study, we assessed hypothesised relations among these
      variables across the life course, using structural equation modelling in a sample
      assessed on dependability (a personality trait related to conscientiousness) in
      childhood, cognitive ability and social class in childhood and older age,
      education, and health and subjective wellbeing in older age. Our models indicated
      that both health and subjective wellbeing in older age were influenced by
      childhood IQ and social class, via education. Some older-age personality traits
      mediated the effects of early-life variables, on subjective wellbeing in
      particular, but childhood dependability did not show significant associations.
      Our results therefore did not provide evidence that childhood dependability
      promotes older-age health and wellbeing, but did highlight the importance of
      other early-life factors, particularly characteristics that contribute to
      educational attainment. Further, personality in later life may mediate the
      effects of early-life factors on health and subjective wellbeing. (c) 2016 The
      Authors. European Journal of Personality published by John Wiley & Sons Ltd on
      behalf of European Association of Personality Psychology.

PMID- 27867260
TI  - Tracking sentence comprehension: Test-retest reliability in people with aphasia
      and unimpaired adults.
AB  - PURPOSE: Visual-world eyetracking is increasingly used to investigate online
      language processing in normal and language impaired listeners. Tracking changes
      in eye movements over time also may be useful for indexing language recovery in
      those with language impairments. Therefore, it is critical to determine the test
      retest reliability of results obtained using this method. METHODS: Unimpaired
      young adults and people with aphasia took part in two eyetracking sessions spaced
      about one week apart. In each session, participants completed a sentence-picture
      matching task in which they listened to active and passive sentences (e.g., The
      [N1+Auxwoman was] [Vvisiting/visited] [NP/PP2(by) the man]) and selected between
      two pictures with reversed thematic roles. We used intraclass correlations (ICCs)
      to examine the test-retest reliability of response measures (accuracy, reaction
      time (RT)) and online eye movements (i.e., the likelihood of fixating the target
      picture in each region of the sentence) in each participant group. RESULTS: In
      the unimpaired adults, accuracy was at ceiling (thus ICCs were not computed),
      with moderate ICCs for RT (i.e., 0.4 - 0.58) for passive sentences and low (<0.4)
      for actives. In individuals with aphasia, test-retest reliability was strong
      (0.59<ICC<0.75) for accuracy and excellent (>0.75) for RT for both sentence
      types. Similarly, for the unimpaired listeners, reliability of eye movements was
      moderate for passive sentences (NP/PP2 region) and low in all regions for active
      sentences. But, for the aphasic participant group, eye movement reliability was
      excellent for passive sentences (in the first second after sentence end) and
      strong for active sentences (V and NP/PP2 regions). CONCLUSION: Results indicated
      moderate-to-low reliability for unimpaired listeners; however, reliable eye
      movement patterns were detected for processes specific to passive sentences
      (e.g., thematic reanalysis). In contrast, individuals with aphasia exhibited
      strong and stable performance across sentence types in response measures and
      online eye movements. These findings indicate that visual-world eyetracking
      provides a reliable measure of online sentence comprehension, and thus may be
      useful for investigating sentence processing changes over time.

PMID- 27867261
TI  - Counselling Psychology in South Africa.
AB  - The origin and development of counselling psychology in South Africa has been
      profoundly influenced by the country's socio-political history and the impact of
      apartheid. As a result of this, counselling psychologists in the country face a
      number of challenges and opportunities for the future. In this paper we provide a
      portrait of counselling psychology in South Africa by describing the current
      character of the specialty and the context in which South African psychologists
      work. We critically discuss the challenges that the specialty faces to meet the
      country's mental health care needs, contest the current Scope of Practice; affirm
      multiculturalism without essentializing or reifying race and ethnicity, and build
      an evidence base for community interventions in the country. We also consider
      how, in the future, counselling psychologists in South Africa may make a more
      meaningful contribution within public health and the country's health care and
      education systems.

PMID- 27867262
TI  - Colonial legacy and the experience of First Nations women in cervical cancer
      screening: a Canadian multi-community study.
AB  - Regular Papanicolaou (Pap) screening has dramatically reduced cervical cancer
      incidence in Canada since the 1950s. However, Indigenous women's rates of
      cervical cancer remain disproportionately high, a factor which is not
      acknowledged in national media or in educational materials reporting Canada's new
      cervical cancer screening guidelines. Here, we present findings from a cervical
      cancer screening initiative in Northwestern Ontario. Based on participatory
      action research, we worked with 10 First Nations communities in the Robinson
      Superior Treaty area to increase awareness of cervical cancer risk, develop
      culturally sensitive tools for screening and education and test the efficacy of
      human papillomavirus (HPV) self-sampling as an alternative to Pap cytology. We
      conducted 16 interviews with health care professionals and 9 focus groups with 69
      women from the communities. A central theme for both health care providers (HCPs)
      and community members was the colonial legacy and its influence on women's
      experiences of cervical cancer screening. This was evidenced by a strong sense of
      body shyness, including shame related to sexuality and sexually transmitted
      infections, concerns about confidentiality in clinical encounters and distrust or
      caution around HCPs. Reaffirming women's traditional caregiving and educational
      roles, enhancing mother and daughter communication, improving cultural
      sensitivity in health care and education and adoption of HPV self-sampling to
      increase women's privacy and control of the cervical cancer screening experience
      were endorsed. We argue that education and screening initiatives must reflect the
      cultural preferences of Indigenous women, empowering them to take control of
      their experiences of health and body in cervical cancer screening.

PMID- 27867264
TI  - Traditional Herbal Formulas to as Treatments for Musculoskeletal Disorders: Their
      Inhibitory Effects on the Activities of Human Microsomal Cytochrome P450s and UDP
      glucuronosyltransferases.
AB  - OBJECTIVE: The aim of this study was to assess the influence of traditional
      herbal formulas, including Bangpungtongseong-san (BPTSS; Fangfengtongsheng-san,
      Bofu-tsusho-san), Ojeok-san (OJS; Wuji-san, Goshaku-san), and Oyaksungi-san
      (OYSGS; Wuyaoshungi-san, Uyakujyunki-san), on the activities of the human
      cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs), which are
      drug-metabolizing enzymes. MATERIALS AND METHODS: The activities of the major
      human CYP450 isozymes (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and
      CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were investigated using in vitro
      fluorescence-based and luminescence-based enzyme assays, respectively. The
      inhibitory effects of the herbal formulas were characterized, and their IC50
      values were determined. RESULTS: BPTSS inhibited the activities of CYP1A2,
      CYP2C19, CYP2E1, and UGT1A1 while it exerted relatively weak inhibition on
      CYP2B6, CYP2C9, CYP2D6, and CYP3A4. BPTSS also negligibly inhibited the
      activities of UGT1A4 and UGT2B7, with IC50 values in the excess of 1000 MUg/mL.
      OJS and OYSGS inhibited the activity of CYP2D6, whereas they exhibited no
      inhibition of the UGT1A4 activity at doses <1000 MUg/mL. In addition, OJS
      inhibited the CYP1A2 activity but exerted a relatively weak inhibition on the
      activities of CYP2C9, CYP2C19, CYP2E1, and CYP3A4. Conversely, OJS negligibly
      inhibited the activities of CYP2B6, UGT1A1, and UGT2B7 with IC50 values in excess
      of 1000 MUg/mL. OYSGS weakly inhibited the activities of CYP1A2, CYP2C19, CYP2E1,
      CYP3A4, and UGT1A1, with a negligible inhibition on the activities of CYP2B6,
      CYP2C9, and UGT2B7, with IC50 values in excess of 1000 MUg/mL. CONCLUSIONS: These
      results provide information regarding the safety and effectiveness of BPTSS, OJS,
      and OYSGS when combined with conventional drugs. SUMMARY: Bangpungtongseong-san
      inhibited the activities of human microsomal CYP1A2, CYP2C19, CYP2E1, and UGT1A1,
      with a negligibly inhibition on the activities of CYP2B6, CYP2C9, CYP2D6, CYP3A4,
      UGT1A4, and UGT2B7Ojeok-san (OJS) inhibited the CYP1A2 and CYP2D6 mediated
      metabolism while showing a comparatively weak inhibition against CYP2B6, CYP2C9,
      CYP2C19, CYP2E1, CYP3A4, and UGT1A1 in human microsomesOyaksungi-san (OYSGS)
      inhibited the activities of human microsomal CYP2D6, with a relatively weak
      inhibition on the activities of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2E1, CYP3A4,
      UGT1A1, and UGT2B7OJS showed no inhibition on the activities of human microsomal
      UGT1A4 and UGT2B7, and OYSGS did not affect the human microsomal UGT1A4 activity.
      Abbreviations used: BPTSS: Bangpungtongseong-san, OJS: Ojeok-san, OYSGS:
      Oyaksungi-san, CYP450s: cytochrome P450s, UGTs: UDP-glucuronosyltransferases,
      MSDs: Musculoskeletal disorders, NSAIDs: nonsteroidal anti-inflammatory drugs,
      EOMCC: 7-ethoxy-methyloxy-3-cyanocoumarin, DBOMF:
      di(benzyloxymethoxy)fluorescein, BOMCC: 7-benzyloxy-4-trifluoromethylcoumarin,
      HPLC: High-performance liquid chromatography, PDA: photo diode array, SEM:
      standard error of the mean, UDPGA: uridine 5'-diphosphoglucuronic acid.

PMID- 27867265
TI  - Alpha-glucosidase Inhibitory and Antioxidant Potential of Antidiabetic Herb
      Alternanthera sessilis: Comparative Analyses of Leaf and Callus Solvent
      Fractions.
AB  - BACKGROUND: Alternanthera sessilis is a medicinal herb which is consumed as
      vegetable and used as traditional remedies of various ailments in Asia and
      Africa. OBJECTIVE: This study aimed to investigate the antiglucosidase and
      antioxidant activity of solvent fractions of A. sessilis leaf and callus.
      MATERIALS AND METHODS: Leaf and callus methanol extracts were fractionated to
      produce hexane, chloroform, ethyl acetate, butanol, and water fractions.
      Antiglucosidase and 1,1-diphenyl-2-picrylhydrazyl scavenging activities as well
      as total phenolic (TP), total flavonoid (TF), and total coumarin (TC) contents
      were evaluated. Lineweaver-Burk plot analysis was performed on leaf and callus
      fractions with the strongest antiglucosidase activity. RESULTS: Leaf ethyl
      acetate fraction (LEF) had the strongest antiglucosidase (EC50 0.55 mg/mL) and
      radical scavenging (EC50 10.81 MUg/mL) activity among leaf fractions. Callus
      ethyl acetate fraction (CEF) and chloroform fraction had the highest
      antiglucosidase (EC50 0.25 mg/mL) and radical scavenging (EC50 34.12 MUg/mL)
      activity, respectively, among callus fractions. LEF and CEF were identified as
      noncompetitive and competitive alpha-glucosidase inhibitors, respectively. LEF
      and CEF had greater antiglucosidase activity than acarbose. Leaf fractions had
      higher phytochemical contents than callus fractions. LEF had the highest TP, TF,
      and TC contents. Antiglucosidase and antioxidant activities of leaf fractions
      correlated with phytochemical contents. CONCLUSION: LEF had potent
      antiglucosidase activity and concurrent antioxidant activity. CEF had the highest
      antiglucosidase activity among all fractions. Callus culture is a promising tool
      for enhancing production of potent alpha-glucosidase inhibitors. SUMMARY: Leaf
      ethyl acetate fraction (LEF) had the strongest antiglucosidase (EC50 0.55 mg/mL)
      and radical scavenging (EC50 10.81 MUg/mL) activity among leaf fractionsCallus
      ethyl acetate fraction (CEF) and chloroform fraction had the highest
      antiglucosidase (EC50 0.25 mg/mL) and radical scavenging (EC50 34.12 MUg/mL)
      activity, respectively, among callus fractionsLEF and CEF were identified as
      noncompetitive and competitive a-glucosidase inhibitors,
      respectivelyAntiglucosidase and antioxidant activities of leaf fractions
      correlated with phytochemical contents. Abbreviations used: LHF: Leaf hexane
      fraction, LCF: Leaf chloroform fraction, LEF: Leaf ethyl acetate fraction, LBF:
      Leaf butanol fraction, LWF: Leaf water fraction, CHF: Callus hexane fraction,
      CCF: Callus chloroform fraction, CEF: Callus ethyl acetate fraction, CBF: Callus
      butanol fraction, CWF: Callus water fraction, TP: Total phenolic, TF: Total
      flavonoid, TC: Total coumarin.

PMID- 27867263
TI  - Interferon-Stimulated Gene 15 Conjugation Stimulates Hepatitis B Virus Production
      Independent of Type I Interferon Signaling Pathway In Vitro.
AB  - Hepatitis B virus (HBV) is an important account of infectious hepatitis and
      interferon (IFN) remains one of the best treatment options. Activation of type I
      IFN signaling pathway leads to expressions of IFN-stimulated genes (ISGs) which
      play important roles in antiviral and immunomodulatory responses to HBV or
      hepatitis C virus (HCV) infection. Our previous studies indicated that ISG15 and
      its conjugation (ISGylation) were exploited by HCV to benefit its replication and
      persistent infection. This study was designed to assess the role of ISG15 and
      ISGylation in HBV infection in vitro. The levels of ISG15 and ISGylation were
      upregulated by ISG15 plasmid transfection into HepG2.2.15 cells. Decreased
      ISGylation was achieved by siRNA targeting UBE1L, the only E1 activating enzyme
      for ISGylation. Overexpression of ISG15 and subsequent ISGylation significantly
      increased the levels of HBV DNA in the culture supernatants although the
      intracellular viral replication remained unaffected. Silencing UBE1L, with
      decreased ISGylation achieved, abrogated this ISGylation-mediated promoting
      effect. Our data indicated that overexpression of ISG15 stimulated HBV production
      in an ISGylation-dependent manner. Identification of ISG15-conjugated proteins
      (either HBV viral or host proteins) may reveal promising candidates for further
      antiviral drug development.

PMID- 27867266
TI  - A New Antifungal Isocoumarin from The Endophytic Fungus Trichoderma Sp. 09 of
      Myoporum bontioides A. Gray.
AB  - BACKGROUND: Myoporum bontioides A. Gray is a commonly used medicinal plant in
      China. Recently, the chemical and bioactive investigations to the endophytic
      fungi of this plant have led to several new compounds with antimicrobial and
      cytotoxic activities. To find out more active molecules, the metabolites of an
      endophytic fungus, Trichoderma sp. 09 from the root of Myoporum bontioides were
      investigated. MATERIALS AND METHODS: The metabolites were isolated by column
      chromatography on silica gel, and their structures were elucidated on the basis
      of spectroscopic analysis[one-dimensional (1D), two-dimensional (2D)-nuclear
      magnetic resonance (NMR), Mass spectrometry (MS)], and by comparison with the
      published data. The dilution method was used for the evaluation of antifungal
      activity. RESULTS: Four metabolites were isolated and identified as:
      dichlorodiaportinolide (1), dichlorodiaportin (2), diaportinol (3), and diaportin
      (4). Compounds 1 and 2 showed weak to high antifungal activities against
      Colletotrichum musae (Berk. and M. A. Curtis) Arx and Rhizoctonia solani Kuhn, as
      compared with the positive control. CONCLUSIONS: Compound 1 was a new isocoumarin
      being worthy of consideration for the development and research of antifungal
      agents. SUMMARY: A new isocoumarin named dichlorodiaportinolide, along with
      dichlorodiaportin, diaportinol, and diaportin were isolated from the endophytic
      fungus Trichoderma sp. 09 of the root of Myoporum
      bontioides.Dichlorodiaportinolide and dichlorodiaportin showed weak to high
      antifungal activities against musae and R. solani (MIC values from 6.25 to 150
      MUg/mL).Dichlorodiaportinolide and dichlorodiaportin were inactive to P. italic
      and F. graminearum (MIC values > 200 MUg/mL). Abbreviations used: IR: Infrared
      Radiation, HR-ESI-MS: High resolution electrospray ionization mass spectroscopy,
      LCMS-IT-TOF: Liquid chromatography mass spectroscopy-Ion trap-Time-of-flight, UV:
      Ultraviolet-visible, HMBC: Heteronuclear multiple bond correlation, NOE: Nuclear
      Overhauser effect.

PMID- 27867267
TI  - Essential Oil Composition, Antimicrobial and Pharmacological Activities of Lippia
      sidoides Cham. (Verbenaceae) From Sao Goncalo do Abaete, Minas Gerais, Brazil.
AB  - BACKGROUND: Lippia sidoides (Verbenaceae) is used in Brazilian folk medicine as
      an antiseptic, and it is usually applied topically on skin, mucous membranes,
      mouth, and throat, or used for vaginal washings. OBJECTIVES: To analyze the
      chemical composition of the essential oil from L. sidoides collected in Sao
      Goncalo do Abaete, Minas Gerais and grown in Hidrolandia, Goias; to evaluate the
      antimicrobial activity of the essential oil, crude ethanol extract, and hexane,
      dichloromethane, ethyl-acetate, and aqueous fractions (AFs); to study the
      antinociceptive, anti-inflammatory, and central nervous system activities of the
      crude ethanol extract. MATERIALS AND METHODS: The essential oils were obtained by
      hydro-distillation using a Clevenger-type apparatus and analyzed by GC/MS. The
      antimicrobial activity in vitro was performed by broth microdilution method. The
      pharmacological tests were performed using female Swiss albino mice. RESULTS: The
      major components of the essential oil were isoborneol (14.66%), bornyl acetate
      (11.86%), alpha-humulene (11.23%), alpha-fenchene (9.32%), and 1.8-cineole
      (7.05%), supporting the existence of two chemotypes of this species. The hexane
      fraction (HF) had good antifungal activity against Cryptococcus sp. ATCC D (MIC =
      31.25 MUg/mL) and Cryptococcus gatti L48 (MIC = 62.5 MUg/mL). In the
      pharmacological tests, the crude ethanol extract presented antinociceptive and
      anti-inflammatory activities. CONCLUSION: Given that the ethanol extract of L.
      sidoides is included in the Formulary of Phytotherapeutic Agents of the Brazilian
      Pharmacopeia as an anti-inflammatory for oral cavities, the present work provides
      scientific evidence to back this use and highlight the importance of selecting
      the appropriate chemotype on the basis of the expected biological response.
      SUMMARY: The major components of the essential oil of L. sidoides were isoborneol
      bornyl acetate, alpha-humulene, alpha-fenchene, and 1.8-cineole. The HF had good
      antifungal activity against Cryptococcus sp. ATCC D and C. gatti L4.The crude
      ethanol extract of L. sidoides presented antinociceptive and anti-inflammatory
      activities.The present work provides scientific evidence of the importance of
      selecting the appropriate chemotype on the basis of the expected biological
      response. Abbreviations used: UFG: Universidade Federal de Goias; HF: hexane
      fraction; DF: dichloromethane fraction; EAF: ethyl acetate fraction; AF: aqueous
      fraction; MeOH: methanol; MIC: minimum inhibitory concentration; ATCC: American
      Type Culture Collection; MH: Muller Hinton; DMSO: dimethyl sulfoxide; RPMI:
      Roswell Park Memorial Institute; NaCl: sodium chloride; MUL: microliters; mL:
      milliliters; MUg: microgram; kg: kilogram; h: hour; min: minute; cm: centimeter;
      COBEA: Brazilian College of Animal Experiments; p.o.:, oral; i.p.:
      intraperitoneal; s.c.: subcutaneous; SEM: standard error of the mean; RI:
      retention indices.

PMID- 27867269
TI  - Platyphylloside Isolated From Betula platyphylla Inhibit Adipocyte
      Differentiation and Induce Lipolysis Via Regulating Adipokines Including
      PPARgamma in 3T3-L1 Cells.
AB  - BACKGROUND: Obesity causes or aggravates many health problems, both independently
      and in association with several pathological disorders, including Type II
      diabetes, hypertension, atherosclerosis, and cancer. Therefore, we screened small
      compounds isolated from natural products for the development of anti-obesity
      drugs. OBJECTIVE: The purpose of this study was to investigate the anti
      adipogenic activities of platyphylloside, diarylheptanoid isolated from Betula
      platyphylla, which was selected based on the screening using 3T3-L1 cells.
      MATERIALS AND METHODS: To evaluate the inhibition of adipocyte differentiation
      and lipolysis, lipid contents of BPP on were measured using Oil Red O staining in
      3T3-L1 cells. The mRNA and protein expression levels of various adipokines were
      measured by Quantitative real-time PCR and Western blotting analysis,
      respectively. RESULTS: Platyphylloside showed significant inhibitory activity on
      adipocyte differentiation in 3T3-L1 cells and suppressed adipocyte
      differentiation even in the presence of troglitazone, a PPARgamma agonist.
      Platyphylloside might suppress adipocyte differentiation through PPARgamma,
      C/EBPalpha, and SREBP1-induced adipogenesis, which is synergistically associated
      with downstream adipocyte-specific gene promoters such as aP2, FAS, SCD-1, LPL,
      and Adiponectin. In addition, platyphylloside affected lipolysis by down
      regulating perilipin and HSL and up-regulating TNFalpha. CONCLUSION: Taken
      together, the results reveal that platyphylloside has anti-adipogenic activity
      and highlight its potential in the prevention and treatment of obesity. SUMMARY:
      The extract of B. platyphylla bark and its isolate, BPP, had anti-adipogenic
      activity in 3T3-L1 cells via suppression of adipocyte differentiation from
      preadipocytes.Treatment with BPP significantly down-regulated the expression of
      PPARgamma, C/EBP, C/EBPbeta, C/EBPdelta, SREBP1c, SCD-1, FAS, aP2 and LPL.BPP
      induced a lipolytic response in mature adipocytes via up-regulation krof TNFa and
      down-regulation of HSL, perilipin, PPARgamma, PDE3B, and Gia1.BPP is a novel
      potential agent in the prevention and treatment of obesity through its anti
      adipogenic activities and lipolysis. Abbreviations used: DMEM: Dulbecco's
      modified Eagle's medium, FBS: fetal bovine serum, ORO: Oil Red O, PBS: phosphate
      buffered saline, RT: room temperature, PPAR: peroxisome proliferator-activated
      receptor, C/EBP: CCAAT/enhancer-binding protein, SREBP1: sterol regulatory
      element binding protein 1, SCD-1: steroyl-coenzyme A desaturase 1, LPL:
      lipoprotein lipase, aP2: adipocyte fatty acid binding protein, FAS: fatty acid
      synthase, HSL: hormone sensitive lipase, Gialpha1: GPT binding protein, PDE3B:
      phosphodiesterase 3B, TNFalpha: tumor necrosis factor alpha, GAPDH:
      glyceraldehyde 3-phosphate dehydrogenase, SD: standard deviation, EGCG:
      epigallocatechin-3-gallate, TZD: thiazolidinediones.

PMID- 27867268
TI  - Composition of The Essential Oil From Danggui-zhiqiao Herb-Pair and Its Analgesic
      Activity and Effect on Hemorheology in Rats With Blood Stasis Syndrome.
AB  - BACKGROUND: Angelica sinensis and Aurantii fructu used in a pair, named Danggui
      Zhiqiao herb-pair (DZHP), which was rich in essential oil and has been adopted to
      promote blood circulation, dispel blood stasis, and relieve pain in traditional
      Chinese medicine (TCM). OBJECTIVE: To analyze the composition and pharmacological
      effects of essential oil from DZHP. MATERIALS AND METHODS: The composition of the
      essential oil from DZHP was analyzed by gas chromatography/mass spectrometry
      (GC/MS). Its analgesic activity was evaluated by acetic acid-induced writhing
      test and hot plate test. The hemorheology test was carried out to evaluate the
      effect on hemorheology in rats with blood stasis syndrome. RESULTS: Twenty-eight
      components were identified and the main components were alpha-pinene (3.07%),
      beta-pinene (2.0%), beta-myrcene (3.71%), D-limonene (49.28%), gamma-terpinen
      (9.53%), alpha-terpinolene (1.80%), alpha-terpineol (2.02%), beta-bisabolene
      (1.13%), butylidenephthalide (1.43%), and Z-ligustilide (16.08%). The
      pharmacology test showed that the essential oil significantly inhibited the
      number of writhes induced by acetic acid with inhibition rate of 44.64% and
      significantly increased hot-plate latency compared with control group from 30 to
      90 min after oral administration of drugs in mice. It could significantly
      decrease plasma viscosity, whole blood relative index at high and low shear rate,
      whole blood reduced viscosity at high and low shear rate, and erythrocyte
      rigidity index in hemorheology test. CONCLUSION: The composition of the essential
      oil of DZHP was determined successfully and it had analgesic and promoting blood
      circulation activities. SUMMARY: Angelica sinensis and Aurantii fructu used in a
      pair, named Danggui-Zhiqiao herb-pair (DZHP), which was rich in Essential oil and
      has been adopted to promote blood circulation, dispel blood stasis and relieve
      pain in traditional Chinese medicine (TCM).Twenty-eight components were
      identified and the main components were alpha-pinene (3.07%), beta-pinene (2.0%),
      beta-myrcene (3.71%), D-limonene (49.28%), gamma-terpinen (9.53%), alpha
      terpinolene (1.80%), alpha-terpineol (2.02%), beta-bisabolene (1.13%),
      butylidenephthalide (1.43%), and Z-ligustilide (16.08%).The essential oil
      significantly inhibited the number of writhes induced by acetic acid and
      increased hot-plate latency compared with control group from 30 min to 90 min
      after oral administration of drugs in mice.The essential oil could significantly
      decrease plasma viscosity (PV), whole blood relative index (WBRI) at high and low
      shear rate, whole blood reduced viscosity (WBRV) at high and low shear rate, and
      erythrocyte rigidity index (ERI) in hemorheology test. Abbreviations used: DZHP:
      Danggui-Zhiqiao herb-pair; TCM: traditional Chinese medicine; GC/MS: gas
      chromatography /mass spectrometry; PV: plasma viscosity; WBRI: whole blood
      relative index; WBRV: whole blood reduced viscosity; ERI: erythrocyte rigidity
      index.

PMID- 27867270
TI  - Preparation of Sesquiterpenoids from Tussilago farfara L. by High-speed Counter
      current Chromatography.
AB  - BACKGROUND: Sesquiterpenoids, such as tussilagone, has effects of raising blood
      pressure, antiplatelet aggregation, and anti-inflammation activities, which is
      regarded as index compound for quality control of Tussilago farfara L. OBJECTIVE:
      This study was aimed to obtain an effective method for fast isolation of
      sesquiterpenoids from T. farfara L. by high-speed counter-current chromatography
      (HSCCC). MATERIALS AND METHODS: A solvent optimization method for HSCCC was
      presented, i.e., the separation factors of compounds after the K values of
      solvent system should be investigated. RESULTS: A ternary solvent system of n
      hexane:methanol:water (5:8:2, v/v/v) was selected and applied for the HSCCC, and
      56 mg of tussilagone (2) was isolated from T. farfara L., along with two other
      sesquiterpenoids 5.6 mg of 2,2-dimethyl-6-acetylchromanone (1) and 22 mg of 14
      acetoxy-7 beta-(3'-ethyl cis-crotonoyloxy)-lalpha-(2'-methylbutyryloxy)
      notonipetranone (3) by HSCCC with high purities. Their chemical structures were
      elucidated by liquid chromatography-mass spectrometry and nuclear magnetic
      resonance experiments. CONCLUSION: These results offered an efficient strategy
      for preparation of potentially health-relevant phytochemicals from T. farfara L.,
      which might be used for further chemical research and pharmacological studies by
      preparative HSCCC. SUMMARY: The real separation efficiency has been verified by
      analytical HSCCC.A solvent optimization method for HSCCC was presented and
      applied to separate and prepare active compounds.A method for rapid and effective
      separation of target compound Tussilagone with high yield and purity from the
      flower buds of Tussilago farfara.Two other compounds 2,2-Dimethyl-6
      acetylchromanone and 14-acetoxy-7beta-(3'-ethyl cis-crotonoyloxy) -lalpha- (2'
      methylbutyryloxy). notonipetranone hasbeen obtained with high purities from
      flower buds of Tussilago farfara. Abbreviations used: HSCCC: High-Speed Counter
      Current Chromatography; LC-MS: Liquid Chromatograph-Mass Spectrometer; NMR:
      Nuclear Magnetic Resonance; TCM: Traditional Chinese Medicine; HPLC: High
      Performance Liquid Chromatography; ESI-MS: Electrospray Ionization Mass
      Spectrometry; PE: petroleum ether.

PMID- 27867271
TI  - Wound Healing Activity and Chemical Standardization of Eugenia pruniformis
      Cambess.
AB  - BACKGROUND: Eugenia pruniformis is an endemic species from Brazil. Eugenia genus
      has flavonoids as one of the remarkable chemical classes which are related to the
      improvement of the healing process. AIMS: To evaluate of wound healing activity
      of E. pruniformis leaves and to identify and quantify its main flavonoids
      compounds. MATERIALS AND METHODS: Wound excision model in rats was used to verify
      the hydroethanolic and ethyl acetate extracts potential. The animals were divided
      in four groups of six and the samples were evaluated until the 15 degrees  day of
      treatment. Hydroxyproline dosage and histological staining with hematoxilin-eosin
      and Sirius Red were used to observe the tissue organization and quantify the
      collagen deposition, respectively. Chemical compounds of the ethyl acetate
      extract were identified by chromatographic techniques and mass spectrometry
      analysis and total flavonoids content was determined by spectrophotometric
      method. The antioxidant activity was determined by oxygen radical absorbing
      capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazylhydrate radical photometric
      (DPPH) assays. RESULTS: The treated group with the ethyl acetate extract showed
      collagen deposition increase, higher levels of hidroxyproline, better tissue
      reorganization and complete remodeling of epidermis. Quercetin, kaempferol and
      hyperoside were identified as main compounds and flavonoids content value was 43%
      (w/w). The ORAC value of the ethyl acetate extract was 0.81+/- 0.05 mmol TE/g
      whereas the concentration to produce 50% reduction of the DPPH was 7.05+/- 0.09
      MUg/mL. CONCLUSION: The data indicate a wound healing and antioxidant activities
      of E. pruniformis. This study is the first report of flavonoids and wound healing
      activity of E. pruniformis. KEY MESSAGES: Eugenia pruniformis extract accelerates
      wound healing in skin rat model, probably due to its involvement with the
      collagen deposition increase, higher levels of hidroxyproline, dermal remodelling
      and potent antioxidant activity. Chemical standardization of the active wound
      healing extract was done. The total flavonoid content was 43% (w/w) and
      quercetin, kaempferol and hyperoside were identified as main compounds. SUMMARY:
      Wound excision model in rats showed the potential wound healing activity of E.
      pruniformis by collagen deposition increase, higher levels of hidroxyproline,
      better tissue reorganization and complete remodeling of epidermis.Flavonoids are
      the main compounds of the endemic E. pruniformis and quercetin, kaempferol and
      hyperoside were identified in ethyl acetate extract by TLC, HPLC-PDA and HRESI-MS
      analysis.The ethyl acetate extract of E. pruniformis showed a potent antioxidant
      activity by ORAC and DPPH assays Abbreviation used: NC: Negative control, PC:
      Positive control, CH: Crude hydroethanolic extract, EA: Ethyl acetate extract,
      TE: Trolox equivalent, mg: Milligram, mM: Millimolar, mL: Milliliter, HPLC-PDA:
      High performance liquid chromatography with a photodiode array detector, HRESI
      MS: High-resolution electrospray ionization mass spectrometry analysis, TLC: Thin
      layer chromatography, ORAC: Oxygen radical absorbance capacity, w/v: Weight per
      volume.

PMID- 27867272
TI  - Oryza sativa (Rice) Hull Extract Inhibits Lipopolysaccharide-Induced Inflammatory
      Response in RAW264.7 Macrophages by Suppressing Extracellular Signal-regulated
      Kinase, c-Jun N-terminal Kinase, and Nuclear Factor-kappaB Activation.
AB  - BACKGROUND: Rice (Oryza sativa) is a major cereal crop in many Asian countries
      and an important staple food source. Rice hulls have been reported to possess
      antioxidant activities. MATERIALS AND METHODS: In this study, we evaluated the
      antiinflammatory effects of rice hull extract and associated signal transduction
      mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. RESULTS:
      We found that rice hull extract inhibited nitric oxide (NO) and prostaglandin E2
      by suppressing the expression of inducible NO synthase and cyclooxygenase-2,
      respectively. The release of interleukin-1beta and tumor necrosis factor-alpha
      was also reduced in a dose-dependent manner. Furthermore, rice hull extract
      attenuated the activation of nuclear factor-kappa B (NF-kappaB), as well as the
      phosphorylation of mitogen-activated protein kinases, extracellular signal
      regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), in LPS-stimulated
      RAW264.7 cells. CONCLUSION: This suggests that rice hull extract decreases the
      production of inflammatory mediators by downregulating ERK and JNK and the NF
      kappaB signal pathway in RAW 264.7 cells. SUMMARY: Rice hull extract inhibits the
      lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages.Rice
      hull extract inhibited nitric oxide and prostaglandin E2 by suppressing the
      expression of inducible NO synthase and cyclooxygenase-2, respectively.Rice hull
      extract exerted anti-inflammatory effect through inhibition of nuclear factor
      kappa B, extracellular signal-regulated kinase and c-Jun N-terminal kinase
      signaling pathways.Rice hull extract may provide a potential therapeutic approach
      for inflammatory diseases. Abbreviations used: COX-2: cyclooxygenase-2, ERK:
      extracellular signal-regulated kinase, IkappaB: inhibitory kappa B, IL-1beta:
      interleukin-1beta, iNOS: inducible NO synthase, JNK: c-Jun N-terminal kinase,
      LPS: lipopolysaccharide, MAPKs: mitogen-activated protein kinases, NF-kappaB:
      nuclear factor-kappaB, NO: nitric oxide, PGE2: prostaglandin E2, RHE: rice hull
      extract, ROS: reactive oxygen species, TNF-alpha: tumor necrosis factor-alpha.

PMID- 27867273
TI  - Soyasaponin Bb Protects Rat Hepatocytes from Alcohol-Induced Oxidative Stress by
      Inducing Heme Oxygenase-1.
AB  - BACKGROUND: It has been known that oxidative stress induced by alcohol played a
      crucial role in the formation of alcoholic liver disease. Although the formation
      mechanisms underlying liver injury induced by alcohol still remained largely
      unknown, it has been considered that oxidative stress played a core role in the
      pathogenesis of hepatocyte damage. OBJECTIVE: The aim of this study was to
      investigate the effects of soyasaponin Bb (Ss-Bb) on oxidative stress in alcohol
      induced rat hepatocyte injury. RESULTS: It has been shown that the administration
      of Ss-Bb could significantly restore antioxidant activity in BRL 3A cells.
      Moreover, the impaired liver function and morphology changes resulting from
      ethanol exposure were improved by Ss-Bb treatment. Treatment with a
      pharmacological inhibitor of haem oxygenase-1 (HO-1) indicated a critical role of
      HO-1 in mediating the protective role. Finally, we found that pretreatment with
      Ss-Bb to ethanol exposure cells increased the expression level of HO-1.
      CONCLUSION: It was suggested that Ss-Bb may protect against alcohol-induced
      hepatocyte injury through ameliorating oxidative stress, and the induction of HO
      1 was an important protective mechanism. SUMMARY: Effects of soyasaponin Bb was
      investigated on oxidative stress in rat hepatocytesCell viability and antioxidant
      capacities were evaluated to determine the effectsThe expression level of HO-1
      was measured to reveal the proptective mechanisms.

PMID- 27867274
TI  - Pharmacognostical Analysis and Protective Effect of Standardized Extract and
      Rizonic Acid from Erythrina velutina against 6-Hydroxydopamine-Induced
      Neurotoxicity in SH-SY5Y Cells.
AB  - BACKGROUND: Erythrina velutina is a tree common in the northeast of Brazil
      extensively used by traditional medicine for the treatment of central nervous
      system disorders. OBJECTIVE: To develop a standardized ethanol extract of E.
      velutina (EEEV) and to investigate the neuroprotective potential of the extract
      and rizonic acid (RA) from E. velutina on neuronal cells. MATERIALS AND METHODS:
      The plant drug of E. velutina previously characterized was used for the
      production of EEEV. Three methods were evaluated in order to obtain an extract
      with higher content of phenols. The neuroprotective effect of standardized EEEV
      (HPLC-PDA) and RA was investigated on SH-SY5Y cell exposure to the neurotoxin 6
      hydroxydopamine (6-OHDA). RESULTS: The powder of the plant drug was classified as
      moderately coarse and several quality control parameters were determined. EEEV
      produced by percolation gave the highest phenol content when related to others
      extractive methods, and its HPLC-PDA analysis allowed to identify four flavonoids
      and RA, some reported for the first time for the species. EEEV and RA reduced
      significantly the neurotoxicity induced by 6-OHDA in SH-SY5Y cells determined by
      the MTT assay and the nitrite concentration. EEEV also showed a free radical
      scavenging activity. CONCLUSION: This is the first pharmacological study about E.
      velutina which used a controlled standardized extract since the preparation of
      the herbal drug. This extract and RA, acting as an antioxidant, presents a
      neuroprotective effect suggesting that they have potential for future development
      as a therapeutic agent in neurodegenerative disease as Parkinson. SUMMARY: The
      powder of Erythrina velutina was classified as moderately coarse and several
      quality-control parameters were determined.Ethanolic extract from E. velutina
      (EEEV) produced by percolation gave the highest phenol content when related to
      others extractive methods and its HPLC-PDA analysis of EEEV allowed to identify
      four flavonoids and rizonic acid (RA), some reported for the first time for the
      species.The EEEV and RA reduced significantly the neurotoxicity induced by 6-OHDA
      in SH-SY5Y cells determined by the MTT assay and the nitrite concentration.The
      EEEV also showed a free radical scavenging activity. Abbreviations used: +/-:
      More or less, %: Percentage,  degrees C: Degree Celsius, <: Less than, MUg:
      Microgram, MUL: Microliter, MUM: Micromol, [1D] MNR: One-dimensional nuclear
      magnetic resonance spectroscopy, [2D] MNR:Two-dimensional nuclear magnetic
      resonance spectroscopy, 6-OHDA: [6-] Hydroxydopamine. Abs: Absorbance, CFU:
      Colony forming units, CH2Cl2: Dichloromethane, CHCl3: Chloroform cmCentimeter,
      DMEM/F12: Dulbecco's Modified Eagle's Medium: Nutrient Mixture F-12. DMSO:
      Dimethyl sulfoxide, DPPH: 1,1-Diphenyl-2-picrylhydrazyl, EAG: Gallic acid
      equivalents, EEEV: Ethanolic extract of Erythrina velutina, EtOAc: Ethyl acetate,
      g: Gram, h: Hour, H2O: Water, HPLC: High-performance liquid chromatography, H
      REIMS: Hydrogen rapid evaporative ionization mass spectrometry, Kg: Kilogram M:
      Molar, m: Metro, MeOH: Methanol, mg: Milligram, min: Minute, mL: Milliliter, mm:
      Millimeter, MTT: Bromide 3 [4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium,
      N: Normal, NBT: Nitroblue tetrazolium, nm: Nanometer, PDA: Photodiode array
      detector, TPC: Total polyphenol content, RA: Rizonic acid, RP: Reverse phase,
      SOD: Superoxide dismutase, v/v: Volume per volume, Vs: Versus W: Watts.

PMID- 27867275
TI  - Improved Oral Bioavailability of Total Flavonoids of Dracocephalum moldavica via
      Composite Phospholipid Liposomes: Preparation, in-vitro Drug Release and
      Pharmacokinetics in Rats.
AB  - BACKGROUND: Dracocephalum moldavica L is a traditional Uygur medicine for
      centuries, total flavonoids extracted from Dracocephalum moldavica are the major
      active ingredients of herbs, which possesses significant medicinal values to
      treat coronart disease and hypertension, due to the glycosyl group on the ring,
      total flavonoids of Dracocephalum moldavica has low hydrophilic and poorly
      absorbed after oral administration, so one way is the formulation of poorly water
      soluble and permeabledrugs with lipids containing formulations such as Composite
      phospholipid liposomes to improve the absorption profile of drug. OBJECTIVES: To
      prepare composite phospholipid liposome (CPL) encapsulatetotal flavonoids extract
      from Dracocephalum moldavica (TFDM), determine its physicochemical properties,
      investigate its in-vitro release and evaluate the pharmacokinetics in Sprague
      Dawley (SD) rats to increase the bioavailability of TFDM-CPL. MATERIAL AND
      METHODS: The TFDMCPL was prepared by the method of ammonium sulfate transmembrane
      gradients. The CPL and TFDM were separated by Sephadex-G50 chromatography. The
      concentration of TFDM in the CPL was detected by HPLC, then the entrapment
      efficiency (EE) was evaluated. And the shape, particle size, zeta potential, drug
      release in vitro of TFDMCPL were investigated, and the pharmacokinetics was
      evaluated by rat jugular vein intubation tube in SD rats. RESULTS: The EE of TFDM
      was 84.17+/-2.2%, mean size of TFDMCPL was 136.2+/-3.7nm, polymey disperse index
      (PDI) was 0.158+/-0.015 and zeta potential was -19.8+/-1.2mV. TFDM-CPLwere found
      to enhance the release of drugs more effectively than TFDM based on the in vitro
      model and Following oral administration of TFDM, the plasma exposures of TFDM-CPL
      was significantly extended, and the mean concentration of TFDM-CPL was
      significantly higher compared to TFDM-solution. TheCmax, t1/2, AUC0-12 h values
      of TFDM for group of TFDM-CPL were siginificantly increased. CONCLUSION: The
      method of ammonium sulfate transmembrane gradients is suitable for preparingTFDM
      CPL. And TFDM-CPL have potential to be used to improve the bioavailability of
      poorly soluble drugs after oral administration. SUMMARY: For the first time,
      composite phospholipid liposomes (CPL) containing total flavonoids of
      Dracocephalum moldavica (TFDM) were developed by method of ammonium sulfate
      transmembrane gradients.The TFDM-CPL was a significant improvement in
      bioavailability compared to the TFDM-solution, with a 10-fold increase in
      relative bioavailability in vivo.The TFDM-CPL was still stable during storage at
      4oC for 6 months. Abbreviations Used: CPL: composite phospholipid liposome.;
      TFDM: Total Flavonoids Extract from Dracocephalum moldavica; SD:Sprague-Dawley;
      EE:entrapment efficiency; PDI: polymey disperse index; TFDM-CPL: Total flavonoid
      extract from Dracocephalum moldavica - composite phospholipid liposome; DM:
      Dracocephalum moldavica L.; SPC: Soybean phospholipid; HSPC: Hydrogenated soya
      phosphatide; PBS: phosphate buffered saline; HPLC: high performance liquid
      chromatography; TEM: transmission electron microscopy; CMC-Na: Carboxy Methyl
      Cellulose-Natrium; AUC: area under the curve.

PMID- 27867276
TI  - Ursolic Acid, a Natural Pentacylcic Triterpene from Ochrosia elliptica and Its
      Role in The Management of Certain Neglected Tropical Diseases.
AB  - BACKGROUND: Leishmaniasis and African trypanosomiasis are recognized as the
      leading causes of mortality and morbidity with the greatest prevalence in the
      developing countries. They affect more than one billion of the poorest people on
      the globe. OBJECTIVE: To find a cheap, affordable, safe, and efficacious
      antileshmanial and antitrypanosomal natural drug and to elucidate its probable
      mode of action. MATERIALS AND METHODS: Phytochemical investigation of the non
      polar fraction of the methanol extract of leaves of Ochrosia elliptica Labill.
      (Apocyanaceae) resulted in the isolation of ursolic acid, which was unambiguously
      determined based on HR-ESI-FTMS, extensive 1D and 2D NMR spectroscopy. It was
      further tested for its cytotoxicity, antimicrobial, antimalarial,
      antileishmanial, and trypanocidal potency. in-silico molecular modeling studies
      were conducted on six vital parasitic enzymes including farnesyl diphosphate
      synthase, N-myristoyl transferase, pteridine reductase 1, trypanothione
      reductase, methionyl-tRNA synthetase, and inosine-adenosine-guanosine nucleoside
      hydrolase to discover its potential mode of action as antitrypanosomal and
      antileishmanial agent. RESULTS: Ursolic acid displayed considerable
      antitrypanosomal and antileishmanial activities with IC50 values ranging between
      1.53 and 8.79 MUg/mL. It showed superior antitrypanosomal activity as compared to
      the standard drug difluoromethylornithine (DFMO), with higher binding affinities
      towards trypanothione reductase and pteridine reductase 1. It displayed free
      binding energy of -30.73 and -50.08 kcal/mole towards the previously mentioned
      enzymes, respectively. In addition, ursolic acid exhibited considerable
      affinities to farnesyl diphosphate synthase, N-myristoyl transferase and
      methionyl-tRNA synthetase with free binding energies ranging from -42.54 to 
      63.93 kcal/mole. CONCLUSION: Ursolic acid offers a safe, effective and cheap
      antitrypanosomal and antileishmanial candidate acting on several key parasitic
      enzymes. SUMMARY: The fresh leaves of Ochrosia elleptica Labill., family
      Apocyanaceae are a reliable source of ursolic acid.Ursolic acid displayed
      considerable antitrypanosomal and antileishmanial activities. It showed superior
      antitrypanosomal activity as compared to difluoromethylornithine (DFMO), potent
      antitrypanosomal reference drug.In silico molecular modeling studies revealed
      that the antileishmanial and antitrypanosomal activities of ursolic acid could be
      partially explained in view of its multiple inhibitory effects on vital parasitic
      enzymes with the highest potency exerted in the inhibition of pteridine reductase
      1 and trypanothione reductase. Abbreviations used: AHT: African Human
      Trypanosomiasis, ATCC: American type cell culture, BuOH: n-butanol, DCM:
      dichloromethane, DFMO: difluoromethylornithine, EtOAc: ethyl acetate, FCS: fetal
      calf serum, HMBC: Heteronuclear Multiple Bond Correlation, HMQC: Heteronuclear
      Multiple-Quantum Correlation, HR-ESI-FTMS: High Resolution Electrospray
      ionozation Mass Spectrometry, MENA: Middle East and North Africa, MeOH: Methanol,
      MRSA: Methicillin-resistant Staphylococcus aureus, NTDs: Neglected tropical
      diseases, TLC: Thin layer chromatography, UA: Ursolic acid, UV: Ultra violet,
      WHO: World Health Organization.

PMID- 27867277
TI  - Characterization and Bioavailability Study of Baicalin-mesoporous Carbon
      Nanopowder Solid Dispersion.
AB  - BACKGROUND: Baicalin is the main bioactive constitute of the dried roots of
      Scutellaria baicalensis and possesses various biological activities. However, the
      poor water solubility and low oral bioavailability limit its efficacy. OBJECTIVE:
      The present study was conducted to enhance the dissolution and oral
      bioavailability of baicalin (BA) through a novel mesoporous carbon nanopowder
      (MCN) drug carrier. MATERIALS AND METHODS: Solid dispersions (SDs) of BA with MCN
      were prepared using a solvent evaporation method. The physical state of the
      formulations was investigated using SEM, differential scanning calorimetry (DSC)
      and powder X-ray diffraction (XRD). The pharmaceutical performance of pure BA,
      physical mixture (PM) and SDs was evaluated by performing an in-vitro dissolution
      test. The pharmacokinetic studies were conducted in SD rats and the analysis of
      the biological samples was performed on an Acquity UPLC-MS system. The intestinal
      and renal toxicity test of MCN was also evaluated. RESULTS: The drug release
      profile indicated that the BA dissolution rate from SDs with a BA/MCN ratio of
      1:6 greatly increased in comparison with that of the pure crystalline drug.
      Furthermore, a pharmacokinetic analysis in rats showed that the BA area under the
      concentration-time curve for SDs of MCN/BA was 1.83 times larger than that of
      pure BA. In comparison with the pure drug, the MCN-BA system significantly
      shortened the time to Tmax and generated higher Cmax. There was no intestinal and
      renal toxicity of MCN. CONCLUSION: These results indicated that the oral
      bioavailability of BA was remarkably improved by the MCN carrier. Additionally,
      intestinal toxicity test showed that MCN produced no toxicity in the
      gastrointestinal tract. Our results show that MCN-based SDs could be used to
      enhance the bioavailability of drugs with poor water solubility. SUMMARY: The
      drug release profile indicated that the BA dissolution rate from SDs with a
      BA/MCN ratio of 1:6 greatly increased in comparison with that of the pure
      crystalline drug.Furthermore, a pharmacokinetic analysis in rats showed that the
      BA area under the concentration-time curve for SDs of MCN/BA was 1.83 times
      larger than that of pure BA.In comparison with the pure drug, the MCN-BA system
      significantly shortened the time to Tmax and generated higher CmaxAbbreviations
      used: BA: baicalin, MCN: mesoporous carbon nanopowder, SDs: solid dispersions,
      SEM: scanning electron microscopy, DSC: differential scanning calorimetry, XRD:
      powder X-ray diffraction, HPLC: high-performance liquid chromatography, PM:
      physical mixture, S.D.: standard deviation, ANOVA: analysis of variance, RSD:
      relative standard deviation, ESI: electrospray ionization, IS: internal standard,
      MRM: multiple reaction monitoring.

PMID- 27867278
TI  - Effect of Methanolic Leaf Extract of Talinum triangulare (Jacq). Willd. on
      Biochemical Parameters in Diet induced Dyslipidemia Wistar Rats.
AB  - OBJECTIVE: To investigate the effect of methanolic leaf extract of Talinum
      triangulare on hematological parameters, enzymatic and non-enzymatic antioxidant
      status, and serum lipid in Wistar rats fed standard laboratory, or 2% cholesterol
      enrich diet. MATERIAL AND METHODS: Wistar rats (180-210g) divided into six groups
      of six animals (males) each were fed 2% cholesterol-enriched diet and orally
      treated with 0.9% saline or extract of Talinum triangulare (250, 500, and 1000
      mg/kg per body weight) daily for eight weeks. Lipid profile, lipid peroxidation
      (MDA), hematological parameters, and their functional indices and serum
      antioxidant enzymes (catalase, glutathione -S-transferase, and superoxide
      dismutase) activities and glutathione status were assessed in normal and diet
      induced hypercholesterolemic extract treated rats and compared with the rats
      treated with 100 mg/kg per bwt standard drug gemfibrozil. RESULTS: A significant
      (P < 0.05) increase in lipid profile (total glyceride, total cholestrol, low
      density lipoprotein, and very low-density lipoprotein), MDA and reduction (P <
      0.05) in enzymatic and nonenzymatic antioxidant status coupled with alterations
      in hematological parameters was observed in the serum of hypercholesterolemic
      rats when compared with animals on a normal diet. Coadministration of methanolic
      leaf extracts of Talinum triangulare or gemfibrozil significantly (P < 0.05)
      restored the elevated serum lipid profile, MDA, and the deranged hematological
      parameters to near normal. The extract also protected against
      hypercholesterolemic-induced diminished enzymatic and nonenzymatic antioxidant
      status. The activities of the plant extract are dose (250, 500, and 1000 mg/kg)
      dependent and it compared favorably with the standard drug gemfibrozil.
      CONCLUSION: The present study suggested that the extract of Talinum triangulare
      might protect against hypercholesterolemic-induced altered lipid profiles,
      oxidative stress, and also improve the status of antioxidant defense system and
      hematopoiesis. SUMMARY: Elevated lipid profile (total glyceride, total
      cholestrol, low-density lipoprotein, and very low-density lipoprotein), lipid
      peroxidation (MDA), and reduced enzymatic and nonenzymatic antioxidant status
      coupled with alterations in hematological parameters was observed in the serum of
      hypercholesterolemic rats when compared with animals on a normal
      dietCoadministration of methanolic leaf extracts of Talinum triangulare
      significantly (P < 0.05) restored the elevated serum lipid profile, MDA, and the
      deranged hematological parameters to near normal.The extract also protected
      against hypercholesterolemic-induced diminished enzymatic and bnonenzymatic
      antioxidant status.The activities of the plant extract was dose-dependent and it
      compared favorably with the standard drug gemfibrozil. Abbreviations used: Lipid
      peroxidation (MDA), (catalase (CAT), glutathione-S-transferase (GST), superoxide
      dismutase (SOD), glutathione (GSH), Thrombocytes indices (PLT), Red blood cell
      (RBC), Packed cell volume (PVC), Mean corpuscular hemoglobin(MCH), Mean
      corpuscular hemoglobin concentration (MCHC), Total glyceride (TG), Very low
      density lipoprotein (VLDL), Total cholesterol (TC), Low density lipoprotein
      (LDL), High density lipoprotein (HDL) and 3-Hydroxy-3-methyl-glutaryl-CoA
      reductase(HMG-CoA).

PMID- 27867279
TI  - Noise Shaping in Neural Populations with Global Delayed Feedback.
AB  - The interplay between intrinsic and network dynamics has been the focus of many
      investigations. Here we use a combination of theoretical and numerical approaches
      to study the effects of delayed global feedback on the information transmission
      properties of neural networks. Specifically, we compare networks of neurons that
      display intrinsic interspike interval correlations (nonrenewal) to networks that
      do not (renewal). We find that excitatory and inhibitory delays can tune
      information transmission by single neurons but not by the entire network. Most
      surprisingly, addition of a delay can change the dependence of the information on
      the coupling strength for renewal neurons and not for nonrenewal neurons. Our
      results show that intrinsic ISI correlations can have nontrivial interactions
      with network-induced phenomena.

PMID- 27867280
TI  - Anti-cancerous triterpenoid saponins from Lecaniodiscus cupanioides.
AB  - From the ethanol extract of the stem of Lecaniodiscus cupanioides Planch, two
      known compounds 1 and 2 were isolated and identified as triterpenoid saponins 3-O
      [alpha-L-arabinofuranosyl- (1->3)-alpha-L-rhamnopyranosyl- (1->2)-alpha-L
      arabinopyranosyl-]-hederagenin and 3-O- [alpha-L-arabinopyranosyl- (1->3)-alpha-L
      rhamnopyranosyl (1->2)-alpha-L-arabinopyranosyl-]-hederagenin. The structures
      were established by physicochemical and spectroscopic investigations (MS and NMR)
      as well as comparison of literature data. The compound 1 exhibited anticancer
      activity against human colon carcinoma H-116, human lung carcinoma A-549 and
      human lung carcinoma HT-29 cell lines with IC50 5.0, 2.5 and 2.5MUg/ml
      respectively and compound 2 exhibited similar activities with IC505.0, 5.0 and
      2.5MUg/ml respectively. This suggests that the isolated triterpenoid saponins may
      be considered as potential anticancer leads for further studies.

PMID- 27867281
TI  - Visiting Mom: A pilot evaluation of a prison-based visiting program serving
      incarcerated mothers and their minor children.
AB  - We describe an evaluation of a prison visiting program, Extended Visiting (EV),
      for incarcerated mothers and their children. Mothers (N = 24) and caregivers (N =
      19) were interviewed regarding experiences with the program. Mothers identified
      benefits including maintaining a relationship with children, physical contact,
      motivation, privacy, peer support, and personal growth. Caregivers echoed
      mothers' appreciation for the opportunity to maintain mother-child relationships
      and physical contact. Mothers identified barriers including desire for overnight
      visits and more age-appropriate activities. Caregivers perceived travel time and
      costs and children's adverse reactions as barriers. When comparing EV to typical
      visiting, participants unanimously preferred EV.

PMID- 27867282
TI  - Is group singing special? Health, well-being and social bonds in community-based
      adult education classes.
AB  - Evidence demonstrates that group singing improves health and well-being, but the
      precise mechanisms remain unknown. Given that cohesive social networks also
      positively influence health, we focus on the social aspects of singing, exploring
      whether improvements in health and well-being are mediated by stronger social
      bonds, both to the group as a whole (collective-bonding) and to individual
      classmates (relational-bonding). To do so, seven newly-formed community-based
      adult education classes (four singing, N=84, and three comparison classes
      studying creative writing or crafts, N=51) were followed over seven months. Self
      report questionnaire data on mental and physical health, well-being, and social
      bonding were collected at Months 1, 3 and 7. We demonstrate that physical and
      mental health and satisfaction with life significantly improved over time in both
      conditions. Path analysis did not show any indirect effects via social bonding of
      Condition on health and well-being. However, higher collective-bonding at
      timepoint 3 significantly predicted increased flourishing, reduced anxiety and
      improved physical health independently of baseline levels. In contrast,
      relational-bonding showed no such effects, suggesting that it is feeling part of
      a group that particularly yields health and well-being benefits. Moreover, these
      results indicate that singing may not improve health and well-being more than
      other types of activities. Nonetheless, these findings encourage further work to
      refine our understanding of the social aspects of community-based adult education
      classes in promoting health, well-being and community cohesion.

PMID- 27867283
TI  - From 'Virgin Births' to 'Octomom': Representations of Single Motherhood via Sperm
      Donation in the UK News.
AB  - The use of sperm donation by single women has provoked public, professional and
      political debate. Newspapers serve as a critical means of both broadcasting this
      debate and effecting a representation of this user group within the public
      sphere. This study uses the theory of social representations to examine how
      single motherhood by sperm donation has been represented in the UK news over
      time. The study sampled news coverage on this topic in eight British newspapers
      during three 4-year periods between the years 1988 and 2012. The dataset of news
      reports (n = 406) was analysed using a qualitative approach. Findings indicated
      that UK media reports of single women using donor sperm are underpinned by
      conventional categories of the 'personal', the 'traditional' and the 'natural'
      that when paired with their corollaries produce a representation of this user
      group as the social 'other'. The amount of coverage on this topic over time was
      found to vary according to the political orientation of different media sources.
      Using key concepts from social representations theory, this article discusses the
      relationship between themata and anchoring in the maintenance of representations
      of the social 'other' in mass mediated communication. Findings are explained in
      relation to theoretical conceptions of the mass media and its position within the
      public sphere. It is argued that the use of personal narratives in news reports
      of single mothers by sperm donation may have significant implications for public
      understandings of this social group. (c) 2016 The Authors. Journal of Community &
      Applied Social Psychology published by John Wiley & Sons Ltd.

PMID- 27867284
TI  - EkoSonic Thrombolysis as a Therapeutic Adjunct in Venous Occlusive Disease.
AB  - The use of ultrasound waves in conjunction with local thrombolysis may accelerate
      clot resolution and serve as an important therapeutic adjunct in the treatment of
      venous occlusive disease. Our goal was to provide a larger sample population over
      a 5-year period to evaluate our experience with the EkoSonic endovascular system
      (EKOS, EKOS Corporation, Bothell, WA). We suspected that ultrasound-accelerated
      thrombolysis (UAT) using EKOS would provide excellent thrombolysis and midterm
      patency rates with minimal thrombolytic complications. A retrospective study was
      conducted to provide a case series with UAT using EKOS. Data were collected over
      a 5-year period. Primary end points included degree of thrombolysis. Secondarily,
      we analyzed thrombolytic usage, complication rates, and midterm patency, over a 1
      year period. A total of 48 limbs were treated with UAT. Forty cases were
      diagnosed as acute, whereas the remaining 8 were chronic. Complete thrombolysis
      was successful in 38/48 (79%) of patients, and partial thrombolysis was
      accomplished in 10/48 (21%) of patients. Overall mean infusion time was 22.4
      hours +/-3.6. There were a total of three complications (6%), all of which were
      minor bleeding. One-year patency was shown to be 87% with no signs of valvular
      reflux. UAT using EKOS demonstrated effective rates of thrombolysis with very few
      complications. In addition, our 1-year patency rates were comparable to published
      data using conventional catheter-directed thrombolysis. UAT provides lytic
      therapy by utilizing the benefits of ultrasonic waves to help augment the
      fibrinolytic process. Our institution currently favors the use of EKOS as the
      treatment of choice in patients that are appropriate thrombolytic candidates.

PMID- 27867285
TI  - Lower Platelet Reactivity Is Associated with Presentation of Unstable Coronary
      Artery Disease.
AB  - In patients with acute coronary syndrome, high platelet reactivity (PR) is
      associated with an increased risk of secondary thrombotic events. However, in
      patients undergoing elective percutaneous coronary intervention (PCI), no
      association between high PR and outcome has been demonstrated. At present, the
      relation of PR and clinical symptoms is unknown. To examine the association of PR
      with clinical indication for diagnostic angiography (stable or unstable coronary
      artery disease [CAD]), taking into account the influence of P2Y12 inhibitors. A
      platelet function score (PFS) was determined in 195 patients by quantifying
      fibrinogen binding and P-selectin expression with flow cytometry. We evaluated
      the PFS with clinical presentation of stable or unstable CAD, angiographic
      severity of CAD, and the incidence of cardiovascular events during 2 years of
      follow-up. All data were analyzed stratified by P2Y12 inhibitor use (long-term
      and preprocedural versus none). Surprisingly, among non-P2Y12 inhibitor users,
      the PFS was lower in patients with unstable CAD compared with stable CAD (5.6 +/-
      1.8 vs. 7.4 +/- 1.6; p = 0.001). Angiographic CAD severity showed no relation
      with PFS. The SYNTAX score tended to be inversely related with PFS: low PFS, 13.2
      (IQR, 11.9-19.1); median PFS, 10.0 (IQR, 5.0-14.0); and high PFS, 8.0 (IQR, 5.0
      13.0), without significance (p = 0.304). Patients with low PFSs required more re
      PCIs than those with median and high PFSs (11.1 vs. 4.7 vs. 0.0%, p = 0.004).
      This association was modified for patients using P2Y12 inhibitors. Among patients
      without P2Y12 inhibitors undergoing coronary angiography, presentation of
      unstable CAD is independently associated with lower PR.

PMID- 27867286
TI  - Basilic Vein Elevation for Arteriovenous Fistula Creation: Results of 60 Cases
      Following 1 Year.
AB  - Basilic vein elevation (BVE) is a procedure where the basilic vein (BV) is
      surgically exposed, mobilized, and elevated into a more superficial position for
      the purpose of facilitating arteriovenous fistula (AVF) cannulation. The purpose
      of this study is to review the use of BVE as an adjunct to fistula maturation.
      Between January 2009 and December 2013, 60 patients received BVE. After
      performing the anastomosis between brachial artery and BV, the elevated vein was
      placed just anterior to the surgical incision, 3 to 4 mm deep. Patients'
      morbidity, mortality, and patency rates were evaluated. The 90-day mortality was
      0%. Maturation rates were 91.6%. The mean time to maturation was 52 days (range,
      25-75 days). Primary patency rate at 12 months was 90% and secondary patency rate
      was 95%. The mean vein size was 4.5 +/- 0.5 mm. AVF surgery via BVE offers
      satisfactory results in patients with chronic hemodialysis.

PMID- 27867287
TI  - Atherosclerosis in Psoriatic Arthritis: A Multiparametric Analysis Using Imaging
      Technique and Laboratory Markers of Inflammation and Vascular Function.
AB  - Cardiovascular disease is one of the leading causes of death in psoriatic
      arthritis (PsA). Pathogenesis of accelerated atherosclerosis in PsA remains to be
      elucidated. Endothelial dysfunction (ED) often precedes manifesting
      atherosclerosis. This study aims to assess carotid intima-media thickness (CIMT),
      a marker of atherosclerosis in PsA, in context of markers of inflammation and
      vascular function. A cross-sectional study was performed in 18 PsA patients who
      were compared with 18 controls matched for age and sex. Flow-mediated dilatation
      (FMD) assessed by AngioDefender (Everist Health, Ann Arbor, MI), endothelial
      progenitor cells (EPCs) quantified by flow cytometry and CIMT measured
      ultrasonographically. Inflammatory measures included disease activity score of 28
      joints count and disease activity index in psoriatic arthritis. We also assayed
      markers of inflammation, including C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), proinflammatory cytokines (interleukin [IL]-1, IL-6,
      and tumor necrosis factor [TNF]-alpha), and endothelial dysfunction, including
      lipids, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion
      molecule 1 (VCAM-1), and EPCs. CIMT is significantly higher in PsA patients
      compared with controls (0.062 +/- 0.18 vs. 0.045 +/- 0.10 cm, p < 0.01) whereas
      FMD%, EPCs%, and high-density lipoproteins (HDL) cholesterol are significantly
      reduced in PsA compared with controls (p < 0.05). Compared with controls, PsA
      patients had significantly increased concentrations of ESR, CRP, TNF-alpha, IL-6,
      ICAM-1, and VCAM-1. In PsA, CIMT positively correlated with IL-6 and ICAM-1 and
      inversely correlated with FMD, HDL, and EPCs (p < 0.05). In PsA, FMD and CIMT
      were impaired, indicating endothelial dysfunction and accelerated
      atherosclerosis, respectively. PsA-related inflammatory mechanisms (TNF-alpha, IL
      6) and markers of vascular function (CRP, ICAM-1, and EPCs) may all be involved
      in the development of vascular disease in PsA. Cytokine-triggered inflammation
      upregulates expression of adhesion molecules, depletes EPCs with endothelial
      dysfunction, and increased CIMT in PsA.

PMID- 27867288
TI  - Visual-Functional Mismatch Between Coronary Angiography, Fractional Flow Reserve,
      and Quantitative Coronary Angiography.
AB  - Anatomical and functional mismatches are not uncommon in the assessment of
      coronary lesions. The aim of this study was to identify clinical and lesion
      specific factors affecting angiographic, anatomical, and functional mismatch in
      intermediate coronary lesions. In patients who underwent coronary angiography for
      clinical reasons, fractional flow reserve (FFR), and quantitative coronary
      angiography (QCA) analyses for intermediate stenotic lesions were performed
      simultaneously. Mismatches between the measured values were analyzed. A total of
      95 intermediate lesions were assessed simultaneously by visual angiography, FFR,
      and QCA. The visual-FFR mismatch was found in 40% of the lesions while reverse
      visual-FFR mismatch was determined in nearly 14% of the lesions. Mismatch and
      reverse mismatch between FFR and QCA parameters were observed in 10 and 23% of
      the lesions. FFR value was significant in 32% of the lesions while visually
      significant stenosis was shown in 61% of the lesions. Among the visual-FFR
      reverse mismatch group, the prevalence of culprit lesions within the left
      anterior descending (LAD) was significantly higher than other vessels (p value <
      0.02). There were high frequencies of angiographic, QCA, and functional
      mismatches in analyses of intermediate coronary lesions. LAD lesions showed the
      highest mismatch. Angiographic or QCA estimation of lesion severity has
      consistently resulted in inappropriate stenting of functionally nonsignificant
      lesions or undertreatment of significant lesions based on FFR.

PMID- 27867289
TI  - Amplatzer Cardiac Plug for Stroke Prevention in Patients with Atrial Fibrillation
      and Bigger Left Atrial Appendix Size.
AB  - Left atrial appendage (LAA) dimensions have been shown as an independent
      predictor of higher risk for stroke in AF patients. Little data exist on the
      outcomes after LAA closure in patients with nonvalvular atrial fibrillation
      (NVAF) who have relatively bigger LAA size. This study aims to evaluate the
      results associated with LAA closure with the Amplatzer cardiac plug (ACP, AGA,
      St. Jude Medical, Minneapolis, MN) in bigger LAA size. A total of 25 patients
      with NVAF underwent LAA closure with the ACP device. All patients received short
      term (up to 3 months) dual-antiplatelet therapy (clopidogrel and aspirin) after
      the procedure and aspirin only thereafter. A transesophageal echocardiography was
      performed in all patients at the 3- and 6-month follow-ups. No patient was lost
      to follow-up (>= 12 months in all patients). The mean age, CHA2DS2-VASc score,
      and HAS-BLED score were 66.2 +/- 8.79 years; 3.2 +/- 1.46 and 2.4 +/- 1.0,
      respectively. The average sizes of the LAA landing zone and ostium were 23.08 +/-
      5.0 and 24.9 +/- 4.4 mm, respectively. The procedure was successful in 23 (92%)
      patients and was canceled in 2 (8%) patients due to huge LAA dimensions. In 56%
      of the patients "pull and release" technique is needed to appropriately implant
      the ACP. During a mean follow-up of 12 months, no cases of periprocedural stroke
      and no mortality were observed. In patients with NVAF at high risk of
      cardioembolic events and big LAA size, LAA closure using the ACP device is safe
      and effective.

PMID- 27867290
TI  - Ranolazine is an Effective and Safe Treatment of Adults with Symptomatic
      Premature Ventricular Contractions due to Triggered Ectopy.
AB  - Early and delayed afterdepolarizations (EAD/DAD) cause triggered ventricular
      ectopy. Because ranolazine (RAN) suppresses EAD/DAD, we postulated that RAN might
      be effective in reducing premature ventricular contractions (PVCs). To assess the
      effect of RAN in patients with symptomatic PVCs due to triggered ectopy and its
      safety and tolerability. A total of 59 patients with symptomatic PVCs were
      identified from full-disclosure Holters. Doses of 500 and 1,000 mg offlabel RAN,
      daily, were given to 34 and 66% patients, respectively, and repeat Holters were
      performed prospectively during mean followup of 3.1 months. The two Holters were
      retrospectively compared. Congestive heart failure (CHF) was defined as symptoms
      including dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and fatigue, with a
      brain natriuretic peptide > 400. Systolic (heart failure with reduced ejection
      fraction) versus diastolic (heart failure with preserved ejection fraction,
      HFpEF) CHF depended upon an echocardiographic left ventricular ejection fraction
      (LVEF) at least 50% by apical two- and four-chamber Simpson's method (HFpEF). The
      mean age of the patients was 63 years, 60% were males, mean left ventricular
      ejection fraction was 60%, with 34% having coronary artery disease, 73% were
      hypertensive, 24% had type 2 diabetic, and 34% were on beta blockers. Upon repeat
      Holters at a mean of 3.1 months after initiating RAN, 95% (56/59) of the patients
      had their PVC count reduced as follows: 24% (14/59) had more than 90% decrease,
      34% (20/59) had 71 to 90% decrease, and 17% (10/59) had 50 to 70% decrease. In
      the entire group, RAN reduced PVCs by 71% (mean: 13,329 to 3,837; p < 0.001).
      Ventricular bigeminy was reduced by 80% (4,168 to 851; p < 0.001), ventricular
      coupletswere reduced by 78% (374 to 81; p < 0.001), and ventricular
      tachycardiawas reduced by 91% (56 to 5; p < 0.001). The PVC reduction was dose
      dependent. Off-label RAN offers an effective and safe pharmacologic treatment for
      symptomatic triggered PVCs. A large, prospective randomized study is needed.

PMID- 27867291
TI  - Ubiquitous Nature of Distal Athero/Thromboembolic Events during Lower Extremity
      Atherectomy Procedures Involving the Superficial Femoral Artery.
AB  - This study aims to evaluate occurrence, size, composition, and clinical
      significance of embolized debris during superficial femoral artery atherectomy
      using all commercially available atherectomy devices. Distal
      athero/thromboembolic events (DATE) are a universal phenomenon in lower extremity
      atherectomy procedures (LEAPs) due to the sheer volume of atheroma and the
      thrombus burden in peripheral arterial disease. Some of these events can be
      clinically significant. We prospectively gathered clinical and histopathological
      data on all commercially available atherectomy devices by using embolic
      protection devices (EPD) in every case. After intervention, the contents of EPD
      were examined both microscopically and macroscopically. Data from 59 consecutive
      patients undergoing LEAP were analyzed. DATE occurred 100% of the time. The
      composition of particulate debris varied with the device used. Grossly visible
      agglomerated debris was captured by the filter in the majority of patients 54/59
      (91.5%). Clinically significant debris, defined by the Preventing Lower Extremity
      Distal Embolization Using Embolic Filter Protection registry as particle diameter
      > 0.2 cm, was found in 33/59 (56%) patients. The size of captured debris
      particles ranged from 0.1 to 2.4 mm. While DATE occurred in all patients,
      clinically significant DATE occurred in 56% patients undergoing LEAP regardless
      of the atherectomy device. In spite of a large fraction of the clinically
      significant debris occurring on our routine dual antiplatelet regimen, no patient
      suffered an amputation. Although DATE was prevented by the use of EPD in all 59
      cases, more data are needed to determine whether the use of EPD translates into a
      long-term clinical benefit. Use of EPD and optimal thromboprophylaxis should be
      considered in patients, especially in the setting of compromised distal runoff.

PMID- 27867292
TI  - New Impella Cardiac Power Device Used in Patient with Cardiogenic Shock due to
      Nonischemic Cardiomyopathy.
AB  - The new percutaneous Impella CP (Cardiac Power; Abiomed, Inc., Danvers, MA) was
      designed to provide a higher level of support than Impella 2.5 (Abiomed, Inc.).
      We present the first documented case of a patient that was transitioned from the
      Impella 2.5 to Impella CP. A 48-year-old male patient with no medical history was
      transferred to our institution with a one day history of worsening shortness of
      breath. The patient was unstable and found to have monomorphic ventricular
      tachycardia at 220 beats/min that was cardioverted to normal sinus rhythm. An
      emergent right and left heart catheterization was performed showing
      nonobstructive coronary artery disease, biventricular failure with a left
      ventricular ejection fraction (LVEF) of 5 to 10%, high pulmonary capillary wedge
      pressure (PCWP) 22 mm Hg, right atrial (RA) pressure 22 mm Hg, and a very low
      cardiac index of 1.0 L/min/m2. Because of severe cardiogenic shock, Impella 2.5
      was inserted providing flow up to 2.1 L/min; however, the patient remained
      unstable and critically ill with severe multiorgan failure. To provide better
      mechanical support, the device was upgraded to the new Impella CP that can
      provide up to 3.5 L/min of cardiac output. Over the course of the next 72 hours,
      the patient showed significant improvement in hemodynamics and cardiac function
      (LVEF 45%), with recovery of liver function. The Impella CP was removed with no
      complications. The new Impella CP was shown to be safe and effective for
      prolonged use in critically ill patients and may significantly improve their
      prognosis.

PMID- 27867293
TI  - Type VI Choledochal Cyst-An Unusual Presentation of Jaundice.
AB  - Choledochal cysts involving the cystic duct are extremely rare, and are usually
      associated with cystic dilatations of the extrahepatic biliary tract. We describe
      a patient who presented with jaundice and was found to have a dilatation of the
      common bile duct on computed tomographic imaging, consistent with a choledochal
      cyst. He underwent a laparoscopic-converted-to-open cholecystectomy with excision
      of the choledochal cyst which was found to involve the cystic duct. Choledochal
      cysts involving the cystic duct are notably missing from the Todani
      classification. Although exceedingly rare, new cases of these types of cysts are
      being reported, in part due to advancement of diagnostic imaging modalities. We
      discuss the current classification scheme for choledochal cysts and we propose an
      expansion of this scheme.

PMID- 27867294
TI  - Novel Technique to Treat Common Femoral Artery Pseudoaneurysm using Angio-Seal
      Closure Device.
AB  - Iatrogenic common femoral artery pseudoaneurysm is a well-described vascular
      access complication. Several methods have been proposed to treat these
      pseudoaneurysms. In this report, we present three cases of successful
      pseudoaneurysm closure using a novel method of retrograde pseudoaneurysm access
      and thrombosis with Angio-Seal (St Jude Medical, St Paul, MN) closure device.
      This technique appears safe, effective, and reduces patient discomfort.

PMID- 27867295
TI  - Siblings' Perceptions of Differential Treatment, Fairness, and Jealousy and
      Adolescent Adjustment: A Moderated Indirect Effects Model.
AB  - Youth's perception of parents' differential treatment (PDT) are associated with
      maladjustment during adolescence. Although the direct relations between PDT and
      youth's maladjustment have been well established, the mechanisms underlying these
      associations remain unclear. We addressed this gap by examining whether sibling
      jealousy accounted for the links between PDT and youth's depressive symptoms,
      self-worth, and risky behaviors. Additionally, we examined whether youth's
      perceptions of fairness regarding their treatment as well as the gender
      constellation of the dyad moderated these indirect relations (i.e., moderated
      indirect effects). Participants were first- and second-born adolescent siblings
      (M = 15.96, SD = .72 years for older siblings, M = 13.48, SD = 1.02 years for
      younger siblings) and their parents from 197 working and middle class European
      American families. Data were collected via home interviews. A series of
      Conditional Process Analyses revealed significant indirect effects of PDT through
      sibling jealousy to all three adjustment outcomes. Furthermore, perceptions of
      fairness moderated the relations between PDT and jealousy, such that the indirect
      effects were only significant at low (-1 SD) and average levels of fairness. At
      high levels of fairness (+1 SD) there was no association between PDT, jealousy,
      and youth adjustment. Taken together, results indicate that youth and parents
      would benefit from engaging in clear communication regarding the reasoning for
      the occurrence of differential treatment, likely maximizing youth and parent
      perceptions of that treatment as being fair, and in turn mitigating sibling
      jealousy and maladjustment.

PMID- 27867296
TI  - Micropositioning and Control of an Underactuated Platform for Microscopic
      Applications.
AB  - For automation of biological experiments at the micro-scale, highly precise
      manipulator equipped with a microscope is required. However, current
      micropositioning stages have several limitations, such as: 1) manual operation,
      2) lack of rotational capability, 3) incompatibility with a microscope, and 4)
      small range of motion (RoM). This research aims to develop a microscope
      compatible XYtheta micropositioning stage with large RoM for phenotyping multiple
      biological samples rapidly for various microscopic applications. An underactuated
      planar mechanism, kinematic analysis, and control of the XYtheta stage are
      presented in this paper. The planar mechanism consists of two piezoelectric
      linear actuators for translational motion capability and two passive revolute
      joints at the tip of each linear actuator for rotational capability. Based on the
      kinematic analysis of the stage, controllability and control strategy of the
      underactuated stage is described. Finally, the feasibility of the
      micropositioning stage for a general positioning and orienting task is verified
      by both simulation and tissue core experiments.

PMID- 27867298
TI  - Prophylactic Bilateral Nipple-sparing Mastectomy and a Staged Breast
      Reconstruction Technique: Preliminary Results.
AB  - More high-risk women with breast cancer are identified using genetic testing at a
      younger age. These young women often opt for prophylactic surgery. Most patients
      are reluctant for extra donor-site scars besides infections and necrosis. In
      order to reduce these risks, a two-stage breast reconstruction technique is used
      for high-risk women with large or ptotic breasts. We presume that this procedure
      will reduce the risk of skin envelope and nipple-areola complex (NAC) necrosis to
      less than 1%. In the first stage, an inferior pedicle reduction is performed to
      obtain large volume reduction with maximal safety for the NAC. The ptosis, skin
      excess, and malpositioning of the NAC are corrected safely at this stage. In the
      second stage, the skin-sparing mastectomy is performed with or without nipple
      sparing. During this procedure, the areola is never removed. A bilateral breast
      reconstruction is then performed with an immediate subpectoral prothesis or
      delayed with the use of a subpectoral tissue expander. In this way, we aim to
      meet the patient's wish to undergo bilateral risk reducing mastectomy in breasts
      that need ptosis correction without donor-site scarring. This article describes
      the procedure and reports the preliminary data.

PMID- 27867297
TI  - Soil stabilization linked to plant diversity and environmental context in coastal
      wetlands.
AB  - BACKGROUND: Plants play a pivotal role in soil stabilization, with above-ground
      vegetation and roots combining to physically protect soil against erosion. It is
      possible that diverse plant communities boost root biomass, with knock-on
      positive effects for soil stability, but these relationships are yet to be
      disentangled. QUESTION: We hypothesize that soil erosion rates fall with
      increased plant species richness, and test explicitly how closely root biomass is
      associated with plant diversity. METHODS: We tested this hypothesis in salt marsh
      grasslands, dynamic ecosystems with a key role in flood protection. Using step
      wise regression, the influences of biotic (e.g. plant diversity) and abiotic
      variables on root biomass and soil stability were determined for salt marshes
      with two contrasting soil types: erosion-resistant clay (Essex, southeast UK) and
      erosion-prone sand (Morecambe Bay, northwest UK). A total of 132 (30-cm depth)
      cores of natural marsh were extracted and exposed to lateral erosion by water in
      a re-circulating flume. RESULTS: Soil erosion rates fell with increased plant
      species richness (R2 = 0.55), when richness was modelled as a single explanatory
      variable, but was more important in erosion-prone (R2 = 0.44) than erosion
      resistant (R2 = 0.18) regions. As plant species richness increased from two to
      nine species.m-2, the coefficient of variation in soil erosion rate decreased
      significantly (R2 = 0.92). Plant species richness was a significant predictor of
      root biomass (R2 = 0.22). Step-wise regression showed that five key variables
      accounted for 80% of variation in soil erosion rate across regions. Clay-silt
      fraction and soil carbon stock were linked to lower rates, contributing 24% and
      31%, respectively, to variation in erosion rate. In regional analysis, abiotic
      factors declined in importance, with root biomass explaining 25% of variation.
      Plant diversity explained 12% of variation in the erosion-prone sandy region.
      CONCLUSION: Our study indicates that soil stabilization and root biomass are
      positively associated with plant diversity. Diversity effects are more pronounced
      in biogeographical contexts where soils are erosion-prone (sandy, low organic
      content), suggesting that the pervasive influence of biodiversity on
      environmental processes also applies to the ecosystem service of erosion
      protection.

PMID- 27867300
TI  - QUIC Transport and Dispersion Modeling of Vehicle Emissions in Cities for Better
      Public Health Assessments.
AB  - The Quick Urban and Industrial Complex (QUIC) plume modeling system is used to
      explore how the transport and dispersion of vehicle emissions in cities are
      impacted by the presence of buildings. Using downtown Philadelphia as a test
      case, notional vehicle emissions of gases and particles are specified as line
      source releases on a subset of the east-west and north-south streets. Cases were
      run in flat terrain and with 3D buildings present in order to show the
      differences in the model-computed outdoor concentration fields with and without
      buildings present. The QUIC calculations show that buildings result in regions
      with much higher concentrations and other areas with much lower concentrations
      when compared to the flat-earth case. On the roads with vehicle emissions, street
      level concentrations were up to a factor of 10 higher when buildings were on
      either side of the street as compared to the flat-earth case due to trapping of
      pollutants between buildings. However, on roads without vehicle emissions and in
      other open areas, the concentrations were up to a factor of 100 times smaller as
      compared to the flat earth case because of vertical mixing of the vehicle
      emissions to building height in the cavity circulation that develops on the
      downwind side of unsheltered buildings. QUIC was also used to calculate
      infiltration of the contaminant into the buildings. Indoor concentration levels
      were found to be much lower than outdoor concentrations because of deposition
      onto indoor surfaces and particulate capture for buildings with filtration
      systems. Large differences in indoor concentrations from building to building
      resulted from differences in leakiness, air handling unit volume exchange rates,
      and filter type and for naturally ventilated buildings, whether or not the
      building was sheltered from the prevailing wind by a building immediately upwind.

PMID- 27867299
TI  - Circulating Phospholipids as Biomarkers of Breast Cancer: A Review.
AB  - Breast cancer is the most common cancer in women and the second leading cause of
      cancer deaths in women. The key to surviving breast cancer is early detection and
      treatment. Current technologies rely heavily on imaging of the breast, and
      although considered the gold standard, they have their limitations. There is a
      need for a more accurate screening test for women of all ages, which can detect
      the cancer at a cellular level and before metastasis. There have been extensive
      studies into markers for breast cancer including protein and nucleic acid
      biomarkers, but to date, these have been unsuccessful. A growing field of
      interest is the association between breast cancer (tissue and cells) and lipids,
      which is documented in the literature, and may be considered as a leading
      candidate in the breast cancer detection space.

PMID- 27867301
TI  - Perioperative Evaluation of Patients with Pulmonary Conditions Undergoing Non
      Cardiothoracic Surgery.
AB  - This review describes the perioperative management of patients with suspected or
      established pulmonary conditions undergoing non-cardiothoracic surgery, with a
      focus on common pulmonary conditions such as obstructive airway disease,
      pulmonary hypertension, obstructive sleep apnea, and chronic hypoxic respiratory
      conditions. Considering that postoperative pulmonary complications are common and
      given the increasing number of surgical procedures and the size of the aging
      population, familiarity with current guidelines for preoperative risk assessment
      and intra- and postoperative patient management is recommended to decrease the
      morbidity and mortality. In particular, smoking cessation and pulmonary
      rehabilitation are perioperative strategies for improving patients' short- and
      long-term outcomes. Understanding the potential risk for pulmonary complications
      allows the medical team to appropriately plan the intra- and postoperative care
      of each patient.

PMID- 27867303
TI  - DNA Methylation of Cellular Retinoic Acid-Binding Proteins in Cervical Cancer.
AB  - This study determined the methylation status of cellular retinoic acid-binding
      protein (CRABP) gene promoters and associated them with demographic
      characteristics, habits, and the presence of human papilloma virus (HPV) in
      patients with cervical cancer (CC), low and high squamous intraepithelial
      lesions, and no intraepithelial lesion. Women (n = 158) were selected from the
      Colposcopy Clinic of Sanitary Jurisdiction II in Ciudad Juarez, Chihuahua,
      Mexico. Demographic characteristics and habit information were collected.
      Cervical biopsy and endocervical scraping were used to determine methylation in
      promoter regions by methylation-specific polymerase chain reaction technique. We
      found hemi-methylation patterns in the promoter regions of CRABP1 and CRABP2;
      there was 28.5% hemi-methylation in CRABP1 and 7.0% in that of CRABP2.
      Methylation in CRABP1 was associated with age (>=35 years, P = 0.002), family
      history of cancer (P = 0.032), the presence of HPV-16 (P = 0.013), and no alcohol
      intake (P = 0.035). These epigenetic changes could be involved in the CC process,
      and CRABP1 has the potential to be a predictive molecular marker of retinoid
      therapy response.

PMID- 27867304
TI  - Relationships of Reproductive Traits With the Phylogeny of the African Noctuid
      Stem Borers.
AB  - The display of the reproductive behavior in most noctuid Lepidoptera follows a
      diel periodicity and is limited to a precise period of either the day or the
      night. These behavioral traits and the sex pheromone chemistry can be species
      specific and thus might be linked to the phylogeny. The objective of this study
      was to test the relationship of these reproductive traits with phylogeny. The
      study was undertaken using eight closely related species of noctuid stem borers,
      which are easy to rear under artificial conditions, namely, Busseola fusca, B.
      nairobica, B. sp. nr. segeta, Manga melanodonta, M. sp. nr. nubifera, Pirateolea
      piscator, Sesamia calamistis, and S. nonagrioides. For each species, the adult
      emergence period, the mating time, and the oviposition period were estimated,
      referred as biological traits. The components of the sex pheromones emitted by
      the females of each species were also analyzed by gas chromatography-mass
      spectrometry. Among the biological traits measured, only those linked to the
      oviposition pattern (timing and egg loads per night) were significantly
      correlated with the phylogeny of these species. For the sex pheromone components,
      among the 13 components identified in all species, only four, namely, Z9
      tetradecenyl acetate (Z9-TDA), Z11-TDA, E11-TDA, and Z11-hexadecenyl acetate (Z11
      HDA), showed the highest significant correlations with the phylogeny. These
      results suggest that among the different reproductive traits evaluated, only few
      are phylogenetically constrained. Their involvement in the reinforcement of
      ecological speciation in noctuid stem borers is discussed.

PMID- 27867305
TI  - Pulmonary Hypertension in Heart Failure Patients Presenting at OAUTHC, Ile-Ife,
      Nigeria.
AB  - BACKGROUND: Pulmonary hypertension (PH) is common in heart failure patients.
      Literature on PH in heart failure is sparse in Nigeria. This study was carried
      out to determine the prevalence of PH in heart failure patients and ascertain the
      relationship between left ventricular systolic and diastolic function and the
      degree of PH. METHODS: A total of 125 heart failure patients had echocardiography
      done. PH was diagnosed using tricuspid regurgitation jet and pulmonary ejection
      jet profile. RESULTS: PH was present in 70.4% of heart failure patients.
      Estimated mean pulmonary arterial pressure increased with increasing severity of
      systolic and diastolic dysfunction and had significantly negative correlation
      with ejection fraction, fractional shortening, and early mitral annular tissue
      diastolic velocity (E'), but positive correlation with left ventricular end
      systolic volume, right ventricular dimension, transmitral E to A ratio, and E/E'
      ratio. CONCLUSION: PH is very common in heart failure and has significant
      relationship with left ventricular function.

PMID- 27867302
TI  - Current and Emerging Uses of Statins in Clinical Therapeutics: A Review.
AB  - Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3
      methyl-glutaryl-coenzyme A reductase, are commonly administered to treat
      atherosclerotic cardiovascular disease. Statin use may expand considerably given
      its potential for treating an array of cholesterol-independent diseases. However,
      the lack of conclusive evidence supporting these emerging therapeutic uses of
      statins brings to the fore a number of unanswered questions including
      uncertainties regarding patient-to-patient variability in response to statins,
      the most appropriate statin to be used for the desired effect, and the efficacy
      of statins in treating cholesterol-independent diseases. In this review, the
      adverse effects, costs, and drug-drug and drug-food interactions associated with
      statin use are presented. Furthermore, we discuss the pleiotropic effects
      associated with statins with regard to the onset and progression of autoimmune
      and inflammatory diseases, cancer, neurodegenerative disorders, strokes,
      bacterial infections, and human immunodeficiency virus. Understanding these
      issues will improve the prognosis of patients who are administered statins and
      potentially expand our ability to treat a wide variety of diseases.

PMID- 27867306
TI  - Case Report of Ectopic Ovarian Pregnancy Following Fresh Embryo Transfer.
AB  - BACKGROUND: Ovarian pregnancy is a rare and challenging clinical phenomenon.
      Recent studies have identified assisted reproductive treatments and infertility
      as risk factors. However, neither a definite mechanism nor clear risk factors
      were identified and therefore prevention strategies are yet unavailable. CLINICAL
      CASE: In this article, we present a case of ovarian pregnancy occurring following
      in vitro fertilization treatment and a fresh embryo transfer. The couple was
      diagnosed with unexplained infertility and no identifiable risk factors for
      extrauterine pregnancy. The diagnosis of ovarian pregnancy was made during
      explorative laparoscopy performed due to suspected extrauterine pregnancy. The
      patient had normal intra- and postoperative course. CONCLUSION: Ovarian pregnancy
      is an infrequent and a challenging diagnosis. Yet, late diagnosis and lack of
      appropriate intervention may have long-term implications. Several mechanisms and
      risk factors are proposed, and their acknowledgment may improve early diagnosis
      and prevention of complications.

PMID- 27867307
TI  - Adequate Vitamin D Intake but Low Serum Levels in Pediatric Asthma Patients: A
      Pilot Study, Alberta Children's Hospital.
AB  - Background. We assessed vitamin D intakes and serum 25(OH) vitamin D levels in
      pediatric asthma patients on moderate-to-high dose inhaled steroids and compared
      them to published findings of healthy children in our city. Methods. Parents
      and/or patients were interviewed to estimate the children's vitamin D intakes
      from foods and supplements (using an adapted validated food frequency
      questionnaire) and asthma duration and management. Vitamin D status: serum 25
      hyroxy vitamin D (25(OH)D) was obtained from the medical records. Results.
      Vitamin D intakes from food and supplements of the asthma patients (n = 20, 742
      +/- 185 IU/day) were significantly higher compared to healthy Canadian children
      (n = 1442, 229 +/- 121 IU/day). Despite higher vitamin D intakes, the children
      had nonsignificantly lower serum 25(OH) vitamin D levels compared to the
      comparison group. Serum 25(OH)D levels increased by 3.6 nmol/L with each 100 IU
      of vitamin D intake (95% Confidence interval = 2.0-4.0, R2 = 0.931, and p =
      0.001). Conclusion. Since adequate vitamin D status in asthma patients is
      necessary to support bone mineral accretion, it is important to achieve adequate
      vitamin D status by checking serum 25(OH)D status and supplement accordingly.

PMID- 27867308
TI  - Effect of N-Methyl-D-Aspartate Receptor Antagonist Dextromethorphan on Opioid
      Analgesia in Pediatric Intensive Care Unit.
AB  - Objective. Pain control is an essential goal in the management of critical
      children. Narcotics are the mainstay for pain control. Patients frequently need
      escalating doses of narcotics. In such cases an adjunctive therapy may be
      beneficial. Dextromethorphan (DM) is NMDA receptor antagonist and may prevent
      tolerance to narcotics; however, its definitive role is still unclear. We sought
      whether dextromethorphan addition could decrease the requirements of fentanyl to
      control pain in critical children. Design. Double-blind, randomized control trial
      (RCT). Setting. Pediatric multidisciplinary ICU in tertiary care center.
      Patients. Thirty-six pediatric patients 2-14 years of age in a multidisciplinary
      PICU requiring analgesia were randomized into dextromethorphan and placebo. The
      subjects in both groups showed similarity in most of the characteristics.
      Interventions. Subjects while receiving fentanyl for pain control received
      dextromethorphan or placebo through nasogastric/orogastric tubes for 96 hours.
      Pain was assessed using FLACC and faces scales. Measurements and Main Results.
      This study found no statistical significant difference in fentanyl requirements
      between subjects receiving dextromethorphan and those receiving placebo (p =
      0.127). Conclusions. Dextromethorphan has no effect on opioid requirement for
      control of acute pain in children admitted with acute critical care illness in
      PICU. The registration number for this trial is NCT01553435.

PMID- 27867310
TI  - The North Wyke Farm Platform: effect of temperate grassland farming systems on
      soil moisture contents, runoff and associated water quality dynamics.
AB  - : The North Wyke Farm Platform was established as a United Kingdom national
      capability for collaborative research, training and knowledge exchange in agro
      environmental sciences. Its remit is to research agricultural productivity and
      ecosystem responses to different management practices for beef and sheep
      production in lowland grasslands. A system based on permanent pasture was
      implemented on three 21-ha farmlets to obtain baseline data on hydrology,
      nutrient cycling and productivity for 2 years. Since then two farmlets have been
      modified by either (i) planned reseeding with grasses that have been bred for
      enhanced sugar content or deep-rooting traits or (ii) sowing grass and legume
      mixtures to reduce nitrogen fertilizer inputs. The quantities of nutrients that
      enter, cycle within and leave the farmlets were evaluated with data recorded from
      sensor technologies coupled with more traditional field study methods. We
      demonstrate the potential of the farm platform approach with a case study in
      which we investigate the effects of the weather, field topography and farm
      management activity on surface runoff and associated pollutant or nutrient loss
      from soil. We have the opportunity to do a full nutrient cycling analysis, taking
      account of nutrient transformations in soil, and flows to water and losses to
      air. The NWFP monitoring system is unique in both scale and scope for a managed
      land-based capability that brings together several technologies that allow the
      effect of temperate grassland farming systems on soil moisture levels, runoff and
      associated water quality dynamics to be studied in detail. HIGHLIGHTS: Can meat
      production systems be developed that are productive yet minimize losses to the
      environment?The data are from an intensively instrumented capability, which is
      globally unique and topical.We use sensing technologies and surveys to show the
      effect of pasture renewal on nutrient losses.Platforms provide evidence of the
      effect of meteorology, topography and farm activity on nutrient loss.

PMID- 27867311
TI  - Spatial variation in soil properties and diffuse losses between and within
      grassland fields with similar short-term management.
AB  - : One of the major challenges for agriculture is to understand the effects of
      agricultural practices on soil properties and diffuse pollution, to support
      practical farm-scale land management. Three conventionally managed grassland
      fields with similar short-term management, but different ploughing histories,
      were studied on a long-term research platform: the North Wyke Farm Platform. The
      aims were to (i) quantify the between-field and within-field spatial variation in
      soil properties by geostatistical analysis, (ii) understand the effects of soil
      condition (in terms of nitrogen, phosphorus and carbon contents) on the quality
      of discharge water and (iii) establish robust baseline data before the
      implementation of various grassland management scenarios. Although the fields
      sampled had experienced the same land use and similar management for at least 6
      years, there were differences in their mean soil properties. They showed
      different patterns of soil spatial variation and different rates of diffuse
      nutrient losses to water. The oldest permanent pasture field had the largest soil
      macronutrient concentrations and the greatest diffuse nutrient losses. We show
      that management histories affect soil properties and diffuse losses. Potential
      gains in herbage yield or benefits in water quality might be achieved by
      characterizing every field or by area-specific management within fields (a form
      of precision agriculture for grasslands). Permanent pasture per se cannot be
      considered a mitigation measure for diffuse pollution. The between- and within
      field soil spatial variation emphasizes the importance of baseline
      characterization and will enable the reliable identification of any effects of
      future management change on the Farm Platform. HIGHLIGHTS: Quantification of soil
      and water quality in grassland fields with contrasting management
      histories.Considerable spatial variation in soil properties and diffuse losses
      between and within fields.Contrasting management histories within and between
      fields strongly affected soil and water quality.Careful pasture management
      needed: the oldest pasture transferred the most nutrients from soil to water.

PMID- 27867309
TI  - Gender Differences in Symptoms, Health-Related Quality of Life, Sleep Quality,
      Mental Health, Cognitive Performance, Pain-Cognition, and Positive Health in
      Spanish Fibromyalgia Individuals: The Al-Andalus Project.
AB  - Objective. To test the gender differences in tenderness, impact of fibromyalgia,
      health-related quality of life, fatigue, sleep quality, mental health, cognitive
      performance, pain-cognition, and positive health in Spanish fibromyalgia patients
      and in age-matched nonfibromyalgia individuals from the same region. To test the
      optimal cut-off score of the different tender points for women and men. Methods.
      A total of 405 (384 women) fibromyalgia versus 247 (195 women) nonfibromyalgia
      control participants from southern Spain (Andalusia) took part in this cross
      sectional study. The outcomes studied were assessed by means of several tests.
      Results. In the fibromyalgia group, men showed better working memory than women
      (all, P < 0.01), whereas sleep latency was lower in women compared to men (P =
      0.013). In the nonfibromyalgia group, men showed higher pain threshold in all the
      tender points (all, P < 0.01), except in right and left lateral epicondyle.
      Furthermore, men showed better working memory than women (all, P < 0.01), whereas
      memory performance was better in women compared to men (all, P <= 0.01).
      Conclusion. The results of the present study do not support consistent evidence
      of gender differences in fibromyalgia-related symptoms. However, it seems that
      detriment of some symptoms (especially pain) in fibromyalgia men compared with
      their nonfibromyalgia counterparts is greater than those of fibromyalgia women
      compared with their nonfibromyalgia peers.

PMID- 27867312
TI  - Sustainable grassland systems: a modelling perspective based on the North Wyke
      Farm Platform.
AB  - The North Wyke Farm Platform (NWFP) provides data from the field- to the farm
      scale, enabling the research community to address key issues in sustainable
      agriculture better and to test models that are capable of simulating soil, plant
      and animal processes involved in the systems. The tested models can then be used
      to simulate how agro-ecosystems will respond to changes in the environment and
      management. In this study, we used baseline datasets generated from the NWFP to
      validate the Soil-Plant-Atmosphere Continuum System (SPACSYS) model in relation
      to the dynamics of soil water content, water loss from runoff and forage biomass
      removal. The validated model, together with future climate scenarios for the
      2020s, 2050s and 2080s (from the International Panel on Climate Change (IPCC)
      Special Report on Emissions Scenarios (SRES): medium (A1B) and large (A1F1)
      emission scenarios), were used to simulate the long-term responses of the system
      with three contrasting treatments on the NWFP. Simulation results demonstrated
      that the SPACSYS model could estimate reliably the dynamics of soil water
      content, water loss from runoff and drainage, and cut biomass for a permanent
      sward. The treatments responded in different ways under the climate change
      scenarios. More carbon (C) is fixed and respired by the swards treated with an
      increased use of legumes, whereas less C was lost through soil respiration with
      the planned reseeding. The deep-rooting grass in the reseeding treatment reduced
      N losses through leaching, runoff and gaseous emissions, and water loss from
      runoff compared with the other two treatments.

PMID- 27867313
TI  - Tool-specific performance of vibration-reducing gloves for attenuating fingers
      transmitted vibration.
AB  - BACKGROUND: Fingers-transmitted vibration can cause vibration-induced white
      finger. The effectiveness of vibration-reducing (VR) gloves for reducing hand
      transmitted vibration to the fingers has not been sufficiently examined.
      OBJECTIVE: The objective of this study is to examine tool-specific performance of
      VR gloves for reducing finger-transmitted vibrations in three orthogonal
      directions (3D) from powered hand tools. METHODS: A transfer function method was
      used to estimate the tool-specific effectiveness of four typical VR gloves. The
      transfer functions of the VR glove fingers in three directions were either
      measured in this study or during a previous study using a 3D laser vibrometer.
      More than seventy vibration spectra of various tools or machines were used in the
      estimations. RESULTS: When assessed based on frequency-weighted acceleration, the
      gloves provided little vibration reduction. In some cases, the gloves amplified
      the vibration by more than 10%, especially the neoprene glove. However, the
      neoprene glove did the best when the assessment was based on unweighted
      acceleration. The neoprene glove was able to reduce the vibration by 10% or more
      of the unweighted vibration for 27 out of the 79 tools. If the dominant vibration
      of a tool handle or workpiece was in the shear direction relative to the fingers,
      as observed in the operation of needle scalers, hammer chisels, and bucking bars,
      the gloves did not reduce the vibration but increased it. CONCLUSIONS: This study
      confirmed that the effectiveness for reducing vibration varied with the gloves
      and the vibration reduction of each glove depended on tool, vibration direction
      to the fingers, and finger location. VR gloves, including certified anti
      vibration gloves do not provide much vibration reduction when judged based on
      frequency-weighted acceleration. However, some of the VR gloves can provide more
      than 10% reduction of the unweighted vibration for some tools or workpieces.
      Tools and gloves can be matched for better effectiveness for protecting the
      fingers.

PMID- 27867314
TI  - DNA Recognition by Hybrid Oligoether-Oligodeoxynucleotide Macrocycles.

PMID- 27867316
TI  - Support for international trade law: The US and the EU compared.
AB  - In this article we compare US and EU support for bilateral and multilateral
      international trade law. We assess the support for international law of both
      trading blocs by focusing on the following four dimensions: leadership, consent,
      compliance and internalization. Although we find strong support for international
      trade law from both the US and the EU in general, we also witness some variation,
      most notably in relation to the design of preferential trade agreements (PTAs)
      and compliance with World Trade Organization (WTO) law. Turning to explaining
      these (moderate) differences, we argue that outcomes in US trade policy can best
      be explained by a domestic political factor, namely the direct influence of
      interest groups. Although the involvement of societal interests also goes a long
      way in explaining EU behavior, it does not tell the entire story. We posit that,
      in EU trade policy, institutions are a particular conditioning factor that needs
      to be stressed. Moreover, we suggest that foreign policy considerations in
      managing trade relations have characterized EU's support for international trade
      law.

PMID- 27867315
TI  - The Diphosphorus Complex [Cp2Mo2(CO)4(eta2-P2)] as a Building Block for the
      Synthesis of Mixed-Hybrid Coordination Polymers.
AB  - The three-component reaction of the tetrahedral diphosphorus complex
      [Cp2Mo2(CO)4(eta2-P2)] (1), with Ag[BF4] (2) in the presence of 2,2'-bipyrimidine
      (3) leads to the formation of the two novel two-dimensional networks 4 and 5.
      Compound 4 is a new two-dimensional organometallic-organic hybrid polymer, while
      derivative 5 represents a unique two-dimensional organometallic-inorganic-organic
      hybrid polymer. These results show the possibility of synthesizing a new class of
      coordination polymers, which could not be obtained from two-component reactions
      with organic molecules in addition of metal ions.

PMID- 27867317
TI  - The Longitudinal Process of Early Parent Involvement on Student Achievement: A
      Path Analysis.
AB  - This longitudinal study investigated the process whereby early parent involvement
      in preschool effects student achievement from kindergarten through 6th grade.
      Participants were 1,539 low-income, mainly African American children and their
      mothers, in the Chicago Longitudinal Study. Program children (N = 989) received
      one or two years of the Child-Parent Center (CPC) program - a preschool
      intervention that strongly promoted parents' development of parent involvement
      skills within the school and at home. Children from similar backgrounds who did
      not attend the CPC, but participated in available local resources (e.g. day
      care), were obtained as a comparison group (N = 550). Path analysis revealed an
      interactive process between parent involvement, academic achievement, and
      children's motivation. Early parent involvement directly influenced kindergarten
      achievement, which in turn influenced first grade student motivation. Highly
      motivated children then encouraged parents to continue involvement. The cyclic
      nature of this process across elementary school was observed. The model accounted
      for 61% of the variance in 6th grade achievement. Findings suggest that early
      parent involvement promoted in the CPC program, sets the stage for subsequent
      parent involvement, student motivation, and academic achievement throughout early
      and middle childhood.

PMID- 27867318
TI  - The Power of Affirming Group Values: Group Affirmation Buffers the Self-Esteem of
      Women Exposed to Blatant Sexism.
AB  - Extending the group affirmation literature to the domain of prejudice, this study
      investigated whether group affirmation buffers the self-esteem of women exposed
      to blatant sexism. In accordance with Self-Affirmation Theory (Steele, 1988) and
      group affirmation research (Sherman et al., 2007), we hypothesized that when one
      aspect of the collective self is threatened (gender identity), self-esteem can be
      maintained via the affirmation of an alternative aspect of the collective self.
      In a 2*2 between-participants design, female students were randomly assigned to
      read about discrimination directed toward women or a non-self-relevant
      disadvantaged group (the Inuit). All then participated in a (fictitious) second
      study, in which half completed a group affirmation manipulation (wrote about the
      top three values of a self-defining group) and half completed a control writing
      exercise. The self-esteem of women who were threatened by sexism, but group
      affirmed, was protected from the negative effects of perceiving sexism.

PMID- 27867319
TI  - "I Got to Know Them in a New Way": Rela(y/t)ing Rhizomes and Community-Based
      Knowledge (Brokers') Transformation of Western and Indigenous Knowledge.
AB  - Drawing on three culturally specific research projects, this paper examines how
      community-based knowledge brokers' engagement in brokering knowledge shaped the
      projects' processes. Informed by Deleuze and Guattari's (1987) conceptualization
      of the "rhizome," we discuss how community knowledge brokers' engagement in open
      research-creation practices embrace the relational foundation of Indigenous
      research paradigms in contrast to mainstream Western research practices that are
      engaged as linear, objective, and outcome-oriented activities. In turn, we offer
      propositions for building team environments where open research-creation
      practices can unfold, informing a periphery of shared space for Indigenous and
      Western paradigms.

PMID- 27867320
TI  - Changes in the Dose-Response Relationship of One Toxicant Under Simultaneous
      Exposure to Another Toxicant.
AB  - We considered, in general form for a 22 full factorial experiment, linear
      approximations of the organism's dose-response relationship for some factors
      operating alone and modification of this relationship by another factor operating
      in the background. A typological classification of such modifications is
      suggested. An analysis of the outcomes obtained in a number of subchronic animal
      experiments on rats in which this response was assessed by changes in a large
      number of biomedical indices revealed that all theoretically possible variants
      (types) of the modification under consideration are actually observed depending
      on a specific index and specific harmful exposure. Statistical significance
      estimation procedures are formulated for each of them.

PMID- 27867321
TI  - Destroying the Linear No-threshold Basis for Radiation Regulation: A Commentary.
AB  - This article suggests five classes of effort that scientists can undertake to
      destroy the linear no-threshold hypothesis as the basis of radiation regulation
      in the United States. These are (1) pressure on regulators such as the Nuclear
      Regulatory Commission, (2) presidential messages, (3) Congressional pressure, (4)
      educate physicians about low-dose radiation, and (5) work with journalists and
      media people.

PMID- 27867322
TI  - A Certified Health Physicist's Reflections on a 40-Year Career in Radiation
      Protection.
AB  - This is a reflection from a certified health physicist regarding his becoming
      aware, during his 40-year career, that the linear no-threshold (LNT) model and
      the associated As Low As Reasonably Achievable concept have no scientific basis
      and make no positive contribution to radiation safety. They should be replaced by
      an alternative, scientifically based model that includes a threshold, below which
      there is no harm, and recognition of hormesis and the adaptive response, which
      reflect the benefits of low-dose and low-dose-rate radiation exposure. Continued
      use of the unscientific LNT model is not conservative, as most regulators
      complacently claim but actually harmful. Examples of these harmful impacts in the
      areas of nuclear power, nuclear medicine, and environmental management are
      included.

PMID- 27867323
TI  - Low-Dose-Rate Irradiation for 1 Hour Induces Protection Against Lethal Radiation
      Doses but Does Not Affect Life Span of DBA/2 Mice.
AB  - Prior findings showed that serum from DBA/2 mice that had been given whole-body
      irradiation for 1 hour at a low dose rate (LDR) of 30 cGy/h induced protection
      against radiation in reporter cells by a mechanism depending on transforming
      growth factor beta3 and inducible nitric oxide synthase activity. In the present
      study, the effect of the 1 hour of LDR irradiation on the response of the
      preirradiated mice to a subsequent lethal dose and on the life span is examined.
      These DBA/2 mice were prime irradiated for 1 hour at 30 cGy/h. Two experiments
      with 9 and 9.5 Gy challenge doses given 6 weeks after priming showed increased
      survival in primed mice compared to unprimed mice followed up to 225 and 81 days
      after challenge irradiation, respectively. There was no overall significant
      difference in life span between primed and unprimed mice when no challenge
      irradiation was given. The males seemed to have a slight increase in lifespan
      after priming while the opposite was seen for the females.

PMID- 27867324
TI  - Predicting Adult Criminal Behavior from Juvenile Delinquency: Ex-Ante vs. Ex-Post
      Benefits of Early Intervention.
AB  - Recent analyses of the long-term societal benefits from early intervention
      (prenatal care, home visitation, and high quality preschool) for at-risk children
      commonly include significant savings to society in the form of reduced juvenile
      delinquency and adult criminal behavior. However, a nontrivial proportion of the
      reported benefits of several early intervention programs are based on forecasts
      of criminal behavior throughout adulthood conditional on intervention effects on
      delinquency in adolescence. Data from the Chicago Longitudinal Study (CLS), an
      investigation of the life course of 1,539 children from low-income families born
      in 1979-1980, are used to investigate the bias resulting from predicting the
      effect of early intervention on adult criminal behavior from the effect on
      delinquency in adolescence. The investigation concludes that the general method
      used to predict adult criminal behavior results in a conservative estimate of the
      reduction in the cost of adult criminal behavior attributed to early
      intervention.

PMID- 27867326
TI  - Towards a Consistent and Scientifically Accurate Drug Ontology.
AB  - Our use case for comparative effectiveness research requires an ontology of drugs
      that enables querying National Drug Codes (NDCs) by active ingredient, mechanism
      of action, physiological effect, and therapeutic class of the drug products they
      represent. We conducted an ontological analysis of drugs from the realist
      perspective, and evaluated existing drug terminology, ontology, and database
      artifacts from (1) the technical perspective, (2) the perspective of pharmacology
      and medical science (3) the perspective of description logic semantics (if they
      were available in Web Ontology Language or OWL), and (4) the perspective of our
      realism-based analysis of the domain. No existing resource was sufficient.
      Therefore, we built the Drug Ontology (DrOn) in OWL, which we populated with NDCs
      and other classes from RxNorm using only content created by the National Library
      of Medicine. We also built an application that uses DrOn to query for NDCs as
      outlined above, available at: http://ingarden.uams.edu/ingredients. The
      application uses an OWL-based description logic reasoner to execute end-user
      queries. DrOn is available at http://code.google.com/p/dr-on.

PMID- 27867325
TI  - PARASITOID VENOM INDUCES METABOLIC CASCADES IN FLY HOSTS.
AB  - Parasitoid wasps inject insect hosts with a cocktail of venoms to manipulate the
      physiology, development, and immunity of the hosts and to promote development of
      the parasitoid offspring. The jewel wasp Nasonia vitripennis is a model
      parasitoid with at least 79 venom proteins. We conducted a high-throughput
      analysis of Nasonia venom effects on temporal changes of 249 metabolites in pupae
      of the flesh fly host (Sarcophaga bullata), over a five-day time course. Our
      results show that venom does not simply arrest the metabolism of the fly host.
      Rather, it targets specific metabolic processes while keeping hosts alive for at
      least five days post venom injection by the wasp. We found that venom: (a)
      Activates the sorbitol biosynthetic pathway while maintaining stable glucose
      levels, (b) Causes a shift in intermediary metabolism by switching to anaerobic
      metabolism and blocking the tricarboxylic acid cycle, (c) Arrests chitin
      biosynthesis that likely reflects developmental arrest of adult fly structures,
      (d) Elevates the majority of free amino acids, and (e) May be increasing
      phospholipid degradation. Despite sharing some metabolic effects with cold
      treatment, diapause, and hypoxia, the venom response is distinct from these
      conditions. Because Nasonia venom dramatically increases sorbitol levels without
      changing glucose levels, it could be a useful model for studying the regulation
      of the sorbitol pathway, which is relevant to diabetes research. Our findings
      generally support the view that parasitoid venoms are a rich source of bioactive
      molecules with potential biomedical applications.

PMID- 27867328
TI  - Association Between Erectile Function and Biomarkers of Subclinical
      Atherosclerosis: A Study Based on Middle-Aged Healthy Men from the General
      Population.
AB  - INTRODUCTION: Epidemiological studies suggest atherosclerosis as a common risk
      factor between cardiovascular diseases and erectile dysfunction (ED). We aimed to
      determine the association between erectile function and the biomarkers of
      subclinical atherosclerosis in 119 middle-aged healthy men from the general
      population. METHODS: Erectile function was assessed using the International Index
      of Erectile Function-5 (IIEF-5). Serum levels of biomarkers of atherosclerosis:
      Apolipoprotein A, Apolipoprotein B, fibrinogen, and C-reactive protein (CRP) were
      measured. In addition, demographic data was collected. RESULTS: The mean (SD) of
      age was 55 years (+/- 4.0). The prevalence of ED was 50%. There was a negative
      significant correlation between IIEF-5 and CRP levels (r = -0.20, p = 0.02), and
      BMI (r = -0.20, p = 0.03), respectively. No significant correlations between IIEF
      5 and serum levels of Apolipoprotein A, Apolipoprotein B, and fibrinogen were
      found (p > 0.05). A positive significant correlation was found between BMI and
      fibrinogen (r = 0.20, p = 0.01), CRP (r = 0.30, p = 0.001). In a multivariate
      logistic regression model with IIEF-5 as the dependent variable, CRP was the only
      biomarker that predicted ED (odds ratio = 1.350; 95 % CI: 1.044-1.754).
      CONCLUSIONS: These results indicate that CRP is a biomarker of subclinical
      atherosclerosis associated with ED. This association seems to be linked to
      greater BMI among such men.

PMID- 27867327
TI  - Unusual Glomus Tumor of the Penis.
AB  - INTRODUCTION: Glomus tumors are benign neoplasms commonly found in subungual
      regions of the extremities and rarely located in the penis. Misdiagnosis of
      glomus tumors is common; therefore, symptoms and clinical presentations should be
      reviewed. OBJECTIVE: The primary objective of this review article is to emphasize
      the pathogenesis, pathology, clinical presentation, symptoms, diagnosis, and
      treatment methods of glomus tumors in order to better identify and manage the
      condition. MATERIALS AND METHODS: Research was conducted using PubMed/Medline.
      The inclusion criteria required glomus tumor to be present on the penis. RESULTS:
      Glomus tumors, which appear as symptomatic or asymptomatic lesions, are
      attributed to dispersion grouping of neoplastic or non-neoplastic lesions in a
      particular area. CONCLUSION: Differential diagnosis of glomus tumors includes
      hemangiomas, neurofibromatosis, epithelial lesions, and spindle-cell lesions.
      Physical examination and histological findings should be used for diagnosis.
      Treatment options can be either conservative or invasive, in which the patient
      undergoes surgical excision.

PMID- 27867329
TI  - Caffeine as a Probable Factor for Increased Risk of OAB Development in Elderly
      People.
AB  - OBJECTIVE: This study was conducted to compare overactive bladder (OAB)
      prevalence among people greater than 60 years of age who intake various doses of
      caffeine, as well as those who abstain from caffeine. PATIENTS AND METHODS: A
      randomized observational study was carried out in Vladivostok Gerontological
      Hospital. A total of 1,098 retired people greater than 60 years of age (659 women
      and 439 men, average age 67.1 years) took part in the study. They were admitted
      to the in-patient department with the purpose of annual physical examination
      performed in accordance with the order of the Ministry of Public Health of the
      Russian Federation. People over age 60, who at the moment of examination were in
      satisfactory health condition, were included into the study. People in which OAB
      had been detected or who used to take antimuscarinic were excluded from the
      study. Assessment tools for examining the patients' lower urinary tract condition
      were as follows: OAB-q SF, urination diaries, and uroflowmetry. RESULTS: In the
      course of the experiment conducted, we found that 1/3 of people, both men and
      women greater than 60 years of age, who did not previously seek medical advice
      due to urination troubles, had symptoms of detrusor overactivity. These symptoms
      were moderate and did not bother patients too much in most cases (63.4%). It was
      also found that most patients consumed no more than 300mg caffeine with beverages
      per day, with 30% and 10% of patients suffering from OAB or severe detrusor
      overactivity, respectively. At the same time, almost 50% of patients taking more
      than 300 mg of caffeine per day suffer from OAB. CONCLUSION: 48.1% of people over
      60 years of age suffering from overactive detrusor symptoms consume greater than
      300 mg caffeine daily, which is significantly higher than that of their peers who
      do not intake excessive amounts of caffeine.

PMID- 27867330
TI  - Use of Caudal Analgesia Supplemented with Low Dose of Morphine in Children Who
      Undergo Renal Surgery.
AB  - INTRODUCTION: To test the efficacy and safety of caudal anesthesia (CA)
      supplemented by low dose morphine in children who undergo renal surgery.
      MATERIALS AND METHODS: Forty patients aged 2 months-14 years were enrolled and
      randomly divided into two groups of 20 patients each: Group A (bupivacaine 0.2%
      with fentanyl); Group B (bupivacaine with morphine). The duration of surgery and
      hospitalization time were recorded. Postoperative pain score was measured by Face
      Legs Activity Cry Consolability scale and Wong-Baker Faces scale for those who
      are older. Overall use of rescue analgesics was calculated. RESULTS: There was no
      statistical difference in the length of surgery, incidence of pruritus,
      postoperative nausea, vomiting and urinary retention between the two groups.
      However the postoperative opioid requirements were significantly higher in Group
      A 1.03 +/- 0.9 mg/kg compared to Group B, in which only one patient required
      opioid therapy (p < 0.0001). Moreover the need for non-opioid rescue analgesic
      was higher in Group A, (36 +/- 5.7 mg/kg of paracetamol) compared to morphine CA
      group there only 26 +/- 3.6 mg/kg required during first 24 h of the postoperative
      period (p = 0.0312). The Face Legs Activity Cry Consolability pain score (1, 4,
      and 24 h after surgery) and Wong-Baker Faces scale were significantly higher in
      Group A. The hospitalization period was shorter in the CA morphine group, but the
      difference did not reach statistical significance. None developed hemodynamic
      instability or respiratory depression. CONCLUSIONS: Our data show that CA
      supplemented with low dose morphine provides a longer duration of analgesia
      without significant side-effects in children undergoing renal surgery.

PMID- 27867331
TI  - The Effectiveness of a Systematic Algorithm for the Management of Vascular
      Injuries during the Laparoscopic Surgery.
AB  - OBJECTIVES: Currently, there is no standardized training protocol to teach
      surgeons how to deal with vascular injuries during laparoscopic procedures. The
      purpose of this study is to develop and evaluate the effectiveness of a
      standardized algorithm for managing vascular injury during laparoscopic
      nephrectomies. MATERIALS AND METHODS: The performance of 6 surgeons was assessed
      during 10 laparoscopic nephrectomies in a porcine model. During the first and
      tenth operations, an injury was made in the renal vein without warning the
      surgeon. After the first procedure, the surgeons were instructed on how to
      proceed in dealing with the vascular injury, according to an algorithm developed
      by the designers of this study. The performance of each surgeon before and after
      learning the algorithm was assessed. RESULTS: After learning the algorithm there
      was a decreased blood loss from 327 +/- 403.11 ml to 37 +/- 18.92 ml (p = 0.031)
      and decreased operative time from 43 +/- 14.53 min to 27 +/- 8.27 min (p =
      0.015). There was also improvement in the time to start lesion repair from 147 +/
      117.65 sec to 51 +/- 39.09 sec (p = 0.025). There was a trend toward improvement
      in the reaction time to the injury (22 +/- 21.55 sec vs. 14 +/- 6.39, p = 0.188),
      the time required to control the bleeding (50 +/- 94.2 sec vs. 14 +/- 6.95 sec, p
      = 0.141), and the total time required to completely repair of the vascular injury
      (178 +/- 170.4 sec vs. 119 +/- 183.87 sec, p = 0.302). CONCLUSION: A standardized
      algorithm may help to reduce the potential risks associated with laparoscopic
      surgery. Further studies will help to refine and determine the benefits of
      standardized protocols such as that developed in this study for the management of
      life-threatening laparoscopic complications.

PMID- 27867332
TI  - Predictive Ability of Preoperative CT Scan in Determining Whether the Adrenal
      Gland is Spared at Radical Nephrectomy.
AB  - INTRODUCTION: The aim of this study was to assess whether preoperative multiple
      detector computed tomography (MDCT) accurately predicts adrenal involvement for
      patients undergoing non-adrenal sparing radical nephrectomy for renal cell
      carcinoma. METHODS AND MATERIALS: A retrospective observational study based on a
      composite patient population of two university teaching hospitals who underwent
      radical nephrectomy. Sensitivity, specificity, overall accuracy, positive and
      negative predictive values and likelihood ratios were calculated from
      radiological reports. RESULTS: Total 579 patients underwent radical nephrectomy,
      of which 199 (34.4%) patients underwent a non-adrenal sparing radical
      nephrectomy, in which 128 (64.3%) were male and 118 (59.3%) were left side
      tumors. Mean tumor size was 8.2 cm (range 1.4-20cm). MDCT was found to have a
      sensitivity of 100% and specificity of 95.2% for identifying adrenal invasion.
      Total 179 patients (89.9%) had a radiographically normal ipsilateral adrenal
      gland, of which none were found to have adrenal involvement. Therefore, the
      negative predictive value of preoperative cross-sectional imaging for
      identification of adrenal involvement was 100%. CONCLUSION: Cross- sectional MDCT
      imaging accurately predicts adrenal involvement and the decision to remove or
      spare the adrenal gland should be made preoperative planning regardless of tumour
      size or location at the time of multi-disciplinary discussion unless there is
      intraoperative evidence of adrenal invasion.

PMID- 27867333
TI  - Association between PSA Levels and Biomarkers of Subclinical Systemic
      Inflammation in Middle-Aged Healthy Men from the General Population.
AB  - INTRODUCTION: This study was aimed to determine the association between PSA
      levels and biomarkers of subclinical systemic inflammation based on data from 119
      middle-aged healthy men from the general population. MATERIALS AND METHODS: Serum
      levels of PSA and biomarkers of systemic inflammation (CRP and fibrinogen) were
      measured. Demographic data were also collected. Subjects were divided into two
      groups according to PSA levels; < 2 ng/ml and >= 2 ng/ml. RESULTS: The mean (SD)
      age of men was 55 +/- 4.0 years. We found a positive significant correlation
      between PSA and fibrinogen levels (r = 0.20, p = 0.04), and between CRP and
      fibrinogen levels (r = 0.60, p = 0.01). On the other hand, no significant
      correlation between PSA and CRP levels was found. Men with PSA values >= 2 ng/ml
      had significantly higher levels of fibrinogen as compared to those with PSA < 2
      ng/ml (2.9 ng/ml vs. 2.4 ng/ml, p = 0.01). In a multivariate regression analysis
      model adjusted for the age of subjects, BMI, marital status, smoking, snuff, and
      alcohol intake with serum levels of PSA as a dependent variable, serum level of
      fibrinogen predicted higher PSA-values (odds ratio = 3.30, 95% CI = 1.05-10.20, p
      = 0.042). CONCLUSIONS: The present results indicate that serum fibrinogen is a
      biomarker of subclinical systemic inflammation associated with PSA elevation
      among middle-aged healthy men from the general population.

PMID- 27867334
TI  - Comparison of the Effect of Lidocaine versus a Lidocaine-Bupivacaine Combination
      in a Periprostatic Nerve Block Undergoing Transrectal Ultrasound-Guided Prostate
      Biopsy: A Double-Blind Randomized Controlled Trial.
AB  - INTRODUCTION: To determine whether a combination of the long acting local
      anesthetic, bupivacaine, and lidocaine is better than lidocaine alone in the long
      term pain control, which is a short-acting anesthetic. MATERIALS AND METHODS: In
      group 1, periprostatic nerve block was applied to both neurovascular areas with
      2% lidocaine (5 ml) in an isotonic solution (5 ml). In group 2, the combination
      of 2% lidocaine (5 ml) and 5mg/ml bupivacaine (5 ml) was used for the PPNB.
      RESULTS: In the first 30 minutes the mean VAS scores of groups 1 and 2 were 2.1
      +/- 0.2 and 1.2 +/- 0.1, respectively (p = 0.002). VAS scores of group II
      determined at 1, 2, 4, 6, and 8 hours after the biopsy were significantly lower
      since it was (p < 0.05). CONCLUSION: While periprostatic nerve block for late
      phase pain control, applying a combination of a long-acting local anesthetic,
      such as bupivacaine, is effective in terms of pain control and patient comfort.

PMID- 27867335
TI  - Pyoderma Gangrenosum in the Urologist Clinic.
AB  - Pyoderma gangrenosum is a rare non-infectious skin disorder. It is often
      associated with systemic diseases, like the inflammatory bowel disease,
      rheumatological disease and (hematological) malignancy. The diagnosis is affirmed
      through a process of elimination and is principally based on clinical
      presentation and course. We present a 59-year-old male with T-cell large granular
      lymphocyte leukemia and pyoderma gangrenosum of penis and scrotum. Finally the
      patient was successfully treated with systemic prednisolone.

PMID- 27867336
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1159/000442846.].

PMID- 27867337
TI  - Oligometastatic Growing Teratoma Syndrome: A Case for an Aggressive Surgical
      Approach.
AB  - Growing teratoma syndrome is an infrequent presentation of testicular cancer. We
      present a case of growing teratoma syndrome in a patient who initially presented
      with clinical stage I nonseminomatous testicular germ cell tumor, who
      subsequently developed large volume oligometastases to the retroperitoneum,
      thorax, and thigh. Despite two regimens of chemotherapy, his disease progressed.
      Complete surgical extirpation of all gross tumors confirmed mature teratoma. An
      aggressive surgical approach, including postchemotherapy resection of all known
      metastatic sites, can provide long-term disease-free survival.

PMID- 27867338
TI  - Bladder Leiomyosarcoma: A Rare, but Aggressive Diagnosis.
AB  - It remains evident in the literature that leiomyosarcomas of the bladder have
      continuously been regarded as highly aggressive tumors associated with a poor
      prognosis. Immediate surgical therapy by radical cystectomy with wide margins is
      warranted as an effective treatment modality and has been associated with longer
      survival rates. Herein, we present the case of a high-grade leiomyosarcoma
      primarily treated with anterior pelvic exenteration and urinary diversion.

PMID- 27867339
TI  - When Recessive Genes Mutate to Dominant Gene Action.

PMID- 27867340
TI  - Changing Paradigms in Down Syndrome: The First International Conference of the
      Trisomy 21 Research Society.
AB  - Down syndrome (DS) is the most common genetic cause of intellectual disability
      (ID) in humans with an incidence of ~1:1,000 live births worldwide. It is caused
      by the presence of an extra copy of all or a segment of the long arm of human
      chromosome 21 (trisomy 21). People with DS present with a constellation of
      phenotypic alterations involving most organs and organ systems. ID is present in
      all people with DS, albeit with variable severity. DS is also the most frequent
      genetic cause of Alzheimer's disease (AD), and ~50% of those with DS will develop
      AD-related dementia. In the last few years, significant progress has been made in
      understanding the crucial genotype-phenotype relationships in DS, in identifying
      the alterations in molecular pathways leading to the various clinical conditions
      present in DS, and in preclinical evaluations of potential therapies to improve
      the overall health and well-being of individuals with DS. In June 2015, 230
      scientists, advocates, patients, and family members met in Paris for the 1st
      International Conference of the Trisomy 21 Research Society. Here, we report some
      of the most relevant presentations that took place during the meeting.

PMID- 27867341
TI  - Disorders of Transcriptional Regulation: An Emerging Category of Multiple
      Malformation Syndromes.
AB  - Some genetic disorders caused by mutations in genes encoding components of the
      transcriptional machinery as well as proteins involved in epigenetic modification
      of the genome share many overlapping features, such as facial dysmorphisms,
      growth problems and developmental delay/intellectual disability. As a basis for
      some shared phenotypic characteristics in these syndromes, a similar
      transcriptome disturbance, characterized by global transcriptional dysregulation,
      is believed to play a major role. In this review article, a general overview of
      gene transcription is provided, and the current knowledge of the mechanisms
      underlying some disorders of transcriptional regulation, such as Rubinstein-
      Taybi, Coffin-Siris, Cornelia de Lange, and CHOPS syndromes, are discussed.

PMID- 27867342
TI  - The Family of Crumbs Genes and Human Disease.
AB  - The family of vertebrate Crumbs proteins, homologous to Drosophila Crumbs (Crb),
      share large extracellular domains with epidermal growth factor-like repeats and
      laminin-globular domains, a single transmembrane domain, and a short
      intracellular C-terminus containing a single membrane proximal
      4.1/ezrin/radixin/moesin-binding domain and PSD-95/Discs large/ZO-1-binding
      motifs. There are 3 Crb genes in humans - Crumbs homolog-1 (CRB1), Crumbs homolog
      2 (CRB2), and Crumbs homolog-3 (CRB3). Bilallelic loss-of-function mutations in
      CRB1 cause visual impairment, with Leber's congenital amaurosis and retinitis
      pigmentosa, whereas CRB2 mutations are associated with raised maternal serum and
      amniotic fluid alpha feto-protein levels, ventriculomegaly/hydrocephalus, and
      renal disease, ranging from focal segmental glomerulosclerosis to congenital
      Finnish nephrosis. CRB3 has not yet been associated with human disease. In this
      review, we summarize the phenotypic findings associated with deleterious sequence
      variants in CRB1 and CRB2. We discuss the mutational spectrum, animal models of
      loss of function for both genes and speculate on the likely mechanisms of
      disease.

PMID- 27867343
TI  - PARK2 Microduplication: Clinical and Molecular Characterization of a Further Case
      and Review of the Literature.
AB  - We report on a patient with psychomotor deficits, language delay, dyspraxia,
      skeletal anomalies, and facial dysmorphisms (hirsutism, right palpebral ptosis, a
      bulbous nasal tip with enlarged and anteverted nares, and a mild prominent
      antihelix stem). Using high-resolution SNP array analysis, we identified a 0.49
      Mb microduplication in chromosome 6q26 inherited from the mother involving the
      PARK2 gene: arr[hg19] 6q26(162,672,821-163,163,143)*3 mat. To the best of our
      knowledge, this is the third patient to date described in whom a 6q26
      microduplication encompassing only the PARK2 gene has been reported in medical
      literature. The PARK2 gene is a neurodevelopmental gene that was initially
      discovered as one of the causes of autosomal recessive juvenile Parkinson disease
      and subsequently reported to be linked to autism spectrum disorders and attention
      deficit hyperactivity disorders. We provide an overview of the literature on
      PARK2 microduplications and further delineate the associated phenotype. Taken
      together, our findings confirm the involvement of this gene in neurodevelopmental
      disorders and are useful to strengthen the hypothesis that, although with
      variable expressivity and incomplete penetrance, the PARK2 microduplication is
      associated with a new emerging neurodevelopmental delay syndrome. However,
      clinical and molecular evaluations of more patients with the microduplication are
      needed for full delineation of this syndrome.

PMID- 27867344
TI  - Distal 7q11.23 Duplication, an Emerging Microduplication Syndrome: A Case Report
      and Further Characterisation.
AB  - Chromosome 7q11.23 duplication syndrome is a well-recognised syndrome which
      involves the duplication of the same genes located in the Williams-Beuren
      critical region. However, in 2010, 4 patients were reported with a
      microduplication only in the HIP1 and YWHAG genes. We refer to this as a distal
      7q11.23 duplication (dup7q11.23D). Here, we report the fifth de novo patient with
      dup7q11.23D, whose symptoms may be explained by YWHAG overexpression as was
      demonstrated recently in mice and obese patients. Finally, further studies will
      be necessary to delineate this emerging microduplication syndrome.

PMID- 27867345
TI  - Language Impairment Resulting from a de novo Deletion of 7q32.1q33.
AB  - We report on a girl who presents with hearing loss, behavioral disturbances
      (according to the Inventory for Client and Agency Planning) as well as motor and
      cognitive delay (according to Battelle Developmental Inventories) which have a
      significant impact on her speech and language abilities [according to the Peabody
      Picture Vocabulary Test (ed 3), and the Prueba de Lenguaje Oral de Navarra
      Revisada (Navarra Oral Language Test, Revised)]. Five copy number variations
      (CNVs) were identified in the child: arr[hg18] 7q32.1q33(127109685-132492196)*1,
      8p23.1(7156900-7359099) *1, 15q13.1(26215673-26884937)*1, Xp22.33(17245-
      102434)*3, and Xp22.33(964441-965024)*3. The pathogenicity of similar CNVs is
      mostly reported as unknown. The largest deletion is found in a hot spot for
      cognitive disease and language impairment and contains several genes involved in
      brain development and function, many of which have been related to developmental
      disorders encompassing language deficits (dyslexia, speech-sound disorder, and
      autism). Some of these genes interact with FOXP2. The proband's phenotype may
      result from a reduced expression of some of these genes.

PMID- 27867346
TI  - An Event-Based Neurobiological Recognition System with Orientation Detector for
      Objects in Multiple Orientations.
AB  - A new multiple orientation event-based neurobiological recognition system is
      proposed by integrating recognition and tracking function in this paper, which is
      used for asynchronous address-event representation (AER) image sensors. The
      characteristic of this system has been enriched to recognize the objects in
      multiple orientations with only training samples moving in a single orientation.
      The system extracts multi-scale and multi-orientation line features inspired by
      models of the primate visual cortex. An orientation detector based on modified
      Gaussian blob tracking algorithm is introduced for object tracking and
      orientation detection. The orientation detector and feature extraction block work
      in simultaneous mode, without any increase in categorization time. An addresses
      lookup table (addresses LUT) is also presented to adjust the feature maps by
      addresses mapping and reordering, and they are categorized in the trained spiking
      neural network. This recognition system is evaluated with the MNIST dataset which
      have played important roles in the development of computer vision, and the
      accuracy is increased owing to the use of both ON and OFF events. AER data
      acquired by a dynamic vision senses (DVS) are also tested on the system, such as
      moving digits, pokers, and vehicles. The experimental results show that the
      proposed system can realize event-based multi-orientation recognition. The work
      presented in this paper makes a number of contributions to the event-based vision
      processing system for multi-orientation object recognition. It develops a new
      tracking-recognition architecture to feedforward categorization system and an
      address reorder approach to classify multi-orientation objects using event-based
      data. It provides a new way to recognize multiple orientation objects with only
      samples in single orientation.

PMID- 27867347
TI  - Susceptibility of Mutant SOD1 to Form a Destabilized Monomer Predicts Cellular
      Aggregation and Toxicity but Not In vitro Aggregation Propensity.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by the rapid and progressive degeneration of upper and lower motor
      neurons in the spinal cord, brain stem and motor cortex. The first gene linked to
      ALS was the gene encoding the free radical scavenging enzyme superoxide dismutase
      1 (SOD1) that currently has over 180, mostly missense, ALS-associated mutations
      identified. SOD1-associated fALS patients show remarkably broad mean survival
      times (<1 year to ~17 years death post-diagnosis) that are mutation dependent. A
      hallmark of SOD1-associated ALS is the deposition of SOD1 into large insoluble
      aggregates in motor neurons. This is thought to be a consequence of mutation
      induced structural destabilization and/or oxidative damage leading to the
      misfolding and aggregation of SOD1 into a neurotoxic species. Here we aim to
      understand the relationship between SOD1 variant toxicity, structural stability,
      and aggregation propensity using a combination of cell culture and purified
      protein assays. Cell based assays indicated that aggregation of SOD1 variants
      correlate closely to cellular toxicity. However, the relationship between
      cellular toxicity and disease severity was less clear. We next utilized mass
      spectrometry to interrogate the structural consequences of metal loss and
      disulfide reduction on fALS-associated SOD1 variant structure. All variants
      showed evidence of unfolded, intermediate, and compact conformations, with
      SOD1G37R, SOD1G93A and SOD1V148G having the greatest abundance of intermediate
      and unfolded SOD1. SOD1G37R was an informative outlier as it had a high
      propensity to unfold and form oligomeric aggregates, but it did not aggregate to
      the same extent as SOD1G93A and SOD1V148G in in vitro aggregation assays.
      Furthermore, seeding the aggregation of DTT/EDTA-treated SOD1G37R with preformed
      SOD1G93A fibrils elicited minimal aggregation response, suggesting that the
      arginine substitution at position-37 blocks the templating of SOD1 onto preformed
      fibrils. We propose that this difference may be explained by multiple strains of
      SOD1 aggregate and this may also help explain the slow disease progression
      observed in patients with SOD1G37R.

PMID- 27867348
TI  - Better Targeting, Better Efficiency for Wide-Scale Neuronal Transduction with the
      Synapsin Promoter and AAV-PHP.B.
AB  - Widespread genetic modification of cells in the central nervous system (CNS) with
      a viral vector has become possible and increasingly more efficient. We previously
      applied an AAV9 vector with the cytomegalovirus/chicken beta-actin (CBA) hybrid
      promoter and achieved wide-scale CNS transduction in neonatal and adult rats.
      However, this method transduces a variety of tissues in addition to the CNS. Thus
      we studied intravenous AAV9 gene transfer with a synapsin promoter to better
      target the neurons. We noted in systematic comparisons that the synapsin promoter
      drives lower level expression than does the CBA promoter. The engineered adeno
      associated virus (AAV)-PHP.B serotype was compared with AAV9, and AAV-PHP.B did
      enhance the efficiency of expression. Combining the synapsin promoter with AAV
      PHP.B could therefore be advantageous in terms of combining two refinements of
      targeting and efficiency. Wide-scale expression was used to model a disease with
      widespread pathology. Vectors encoding the amyotrophic lateral sclerosis (ALS)
      related protein transactive response DNA-binding protein, 43 kDa (TDP-43) with
      the synapsin promoter and AAV-PHP.B were used for efficient CNS-targeted TDP-43
      expression. Intracerebroventricular injections were also explored to limit TDP-43
      expression to the CNS. The neuron-selective promoter and the AAV-PHP.B enhanced
      gene transfer and ALS disease modeling in adult rats.

PMID- 27867349
TI  - Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical Hypoxia
      Induced Apoptosis Through the Akt and PERK Pathways.
AB  - Retinal ganglion cells (RGCs) consume large quantities of energy to convert light
      information into a neuronal signal, which makes them highly susceptible to
      hypoxic injury. This study aimed to investigate the potential protection by
      baclofen, a GABAB receptor agonist of RGCs against hypoxia-induced apoptosis.
      Cobalt chloride (CoCl2) was applied to mimic hypoxia. Primary rat RGCs were
      subjected to CoCl2 with or without baclofen treatment, and RNA interference
      techniques were used to knock down the GABAB2 gene in the primary RGCs. The
      viability and apoptosis of RGCs were assessed using cell viability and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays,
      Hoechst staining, and flow cytometry. The expression of cleaved caspase-3, bcl-2,
      bax, Akt, phospho-Akt, protein kinase RNA (PKR)-like ER kinase (PERK), phospho
      PERK, eIF2alpha, phospho-eIF2alpha, ATF-4 and CCAAT/enhancer-binding protein
      homologous protein (CHOP) were measured using western blotting. GABAB2 mRNA
      expression was determined using quantitative real-time polymerase chain reaction
      (qRT-PCR) analysis. Our study revealed that CoCl2 significantly induced RGC
      apoptosis and that baclofen reversed these effects. CoCl2-induced reduction of
      Akt activity was also reversed by baclofen. Baclofen prevented the activation of
      the PERK pathway and the increase in CHOP expression induced by CoCl2. Knockdown
      of GABAB2 and the inactivation of the Akt pathway by inhibitors reduced the
      protective effect of baclofen on CoCl2-treated RGCs. Taken together, these
      results demonstrate that baclofen protects RGCs from CoCl2-induced apoptosis by
      increasing Akt activity and by suppressing the PERK pathway and CHOP activation.

PMID- 27867350
TI  - Berlyne Revisited: Evidence for the Multifaceted Nature of Hedonic Tone in the
      Appreciation of Paintings and Music.
AB  - In his seminal book on esthetics, Berlyne (1971) posited an inverted-U
      relationship between complexity and hedonic tone in arts appreciation, however,
      converging evidence for his theory is still missing. The disregard of the
      multidimensionality of complexity may explain some of the divergent results.
      Here, we argue that definitions of hedonic tone are manifold and systematically
      examined whether the nature of the relationship between complexity and hedonic
      tone is determined by the specific measure of hedonic tone. In Experiment 1, we
      studied three picture categories with similar affective and semantic contents: 96
      affective environmental scenes, which were also converted into 96 cartoons, and
      96 representational paintings. Complexity varied along the dimension of elements.
      In a between-subjects design, each stimulus was presented for 5 s to 206 female
      participants. Subjective ratings of hedonic tone (either beauty, pleasantness or
      liking), arousal, complexity and familiarity were collected in three conditions
      per stimulus set. Complexity and arousal were positively associated in all
      conditions, with the strongest association observed for paintings. For
      environmental scenes and cartoons, there was no significant association between
      complexity and hedonic tone, and the three measures of hedonic tone were highly
      correlated (all rs > 0.85). As predicted, in paintings the measures of hedonic
      tone were less strongly correlated (all rs > 0.73), and when controlling for
      familiarity, the association with complexity was significantly positive for
      beauty (rs = 0.26), weakly negative for pleasantness (rs = -0.16) and not present
      for liking. Experiment 2 followed a similar approach and 77 female participants,
      all non-musicians, rated 92 musical excerpts (15 s) in three conditions of
      hedonic tone (either beauty, pleasantness or liking). Results indicated a strong
      relationship between complexity and arousal (all rs > 0.85). When controlling for
      familiarity effects, the relationship between complexity and beauty followed an
      inverted-U curve, whereas the relationship between complexity and pleasantness
      was negative (rs = -0.26) and the one between complexity and liking positive (rs
      = 0.29). We relate our results to Berlyne's theory and the latest findings in
      neuroaesthetics, proposing that future studies need to acknowledge the
      multifaceted nature of hedonic tone in esthetic experiences of artforms.

PMID- 27867351
TI  - Advice Taking from Humans and Machines: An fMRI and Effective Connectivity Study.
AB  - With new technological advances, advice can come from different sources such as
      machines or humans, but how individuals respond to such advice and the neural
      correlates involved need to be better understood. We combined functional MRI and
      multivariate Granger causality analysis with an X-ray luggage-screening task to
      investigate the neural basis and corresponding effective connectivity involved
      with advice utilization from agents framed as experts. Participants were asked to
      accept or reject good or bad advice from a human or machine agent with low
      reliability (high false alarm rate). We showed that unreliable advice decreased
      performance overall and participants interacting with the human agent had a
      greater depreciation of advice utilization during bad advice compared to the
      machine agent. These differences in advice utilization can be perceivably due to
      reevaluation of expectations arising from association of dispositional
      credibility for each agent. We demonstrated that differences in advice
      utilization engaged brain regions that may be associated with evaluation of
      personal characteristics and traits (precuneus, posterior cingulate cortex,
      temporoparietal junction) and interoception (posterior insula). We found that the
      right posterior insula and left precuneus were the drivers of the advice
      utilization network that were reciprocally connected to each other and also
      projected to all other regions. Our behavioral and neuroimaging results have
      significant implications for society because of progressions in technology and
      increased interactions with machines.

PMID- 27867353
TI  - Simultaneous Bayesian Estimation of Excitatory and Inhibitory Synaptic
      Conductances by Exploiting Multiple Recorded Trials.
AB  - Advanced statistical methods have enabled trial-by-trial inference of the
      underlying excitatory and inhibitory synaptic conductances (SCs) of membrane
      potential recordings. Simultaneous inference of both excitatory and inhibitory
      SCs sheds light on the neural circuits underlying the neural activity and
      advances our understanding of neural information processing. Conventional
      Bayesian methods can infer excitatory and inhibitory SCs based on a single trial
      of observed membrane potential. However, if multiple recorded trials are
      available, this typically leads to suboptimal estimation because they neglect
      common statistics (of synaptic inputs (SIs)) across trials. Here, we establish a
      new expectation maximization (EM) algorithm that improves such single-trial
      Bayesian methods by exploiting multiple recorded trials to extract common SI
      statistics across the trials. In this paper, the proposed EM algorithm is
      embedded in parallel Kalman filters or particle filters for multiple recorded
      trials to integrate their outputs to iteratively update the common SI statistics.
      These statistics are then used to infer the excitatory and inhibitory SCs of
      individual trials. We demonstrate the superior performance of multiple-trial
      Kalman filtering (MtKF) and particle filtering (MtPF) relative to that of the
      corresponding single-trial methods. While relative estimation error of excitatory
      and inhibitory SCs is known to depend on the level of current injection into a
      cell, our numerical simulations using MtKF show that both excitatory and
      inhibitory SCs are reliably inferred using an optimal level of current injection.
      Finally, we validate the robustness and applicability of our technique through
      simulation studies, and we apply MtKF to in vivo data recorded from the rat
      barrel cortex.

PMID- 27867352
TI  - Aberrant Functional Connectivity between the Amygdala and the Temporal Pole in
      Drug-Free Generalized Anxiety Disorder.
AB  - The amygdala and the dorsolateral prefrontal cortex (DLPFC) play important roles
      in "emotion dysregulation," which has a profound impact on etiologic research of
      generalized anxiety disorder (GAD). The present study analyzed both eyes-open and
      eyes-closed resting state functional MRI (rs-fMRI) of 43 subjects (21 GAD
      patients with medicine free and 22 matched healthy controls). The amygdala and
      the DLPFC were defined as regions of interest (ROI) to analyze functional
      connectivity (FC) in GAD patients compared with healthy controls. The main
      findings revealed GAD patients had increased FC between the amygdala and the
      temporal pole compared to healthy controls, which was found in both eyes-open and
      eyes-closed rs-fMRI. And altered FC between the ROIs and brain regions that
      mainly belonged to the default mode network (DMN) were found. These findings
      suggest that the abnormal FC between the amygdala and the temporal pole may
      contribute to the pathophysiology of GAD, and provide insights into the current
      understanding of the emotion dysregulation of anxiety disorders.

PMID- 27867355
TI  - Methods for Specifying Scientific Data Standards and Modeling Relationships with
      Applications to Neuroscience.
AB  - Neuroscience continues to experience a tremendous growth in data; in terms of the
      volume and variety of data, the velocity at which data is acquired, and in turn
      the veracity of data. These challenges are a serious impediment to sharing of
      data, analyses, and tools within and across labs. Here, we introduce BRAINformat,
      a novel data standardization framework for the design and management of
      scientific data formats. The BRAINformat library defines application-independent
      design concepts and modules that together create a general framework for
      standardization of scientific data. We describe the formal specification of
      scientific data standards, which facilitates sharing and verification of data and
      formats. We introduce the concept of Managed Objects, enabling semantic
      components of data formats to be specified as self-contained units, supporting
      modular and reusable design of data format components and file storage. We also
      introduce the novel concept of Relationship Attributes for modeling and use of
      semantic relationships between data objects. Based on these concepts we
      demonstrate the application of our framework to design and implement a standard
      format for electrophysiology data and show how data standardization and
      relationship-modeling facilitate data analysis and sharing. The format uses HDF5,
      enabling portable, scalable, and self-describing data storage and integration
      with modern high-performance computing for data-driven discovery. The BRAINformat
      library is open source, easy-to-use, and provides detailed user and developer
      documentation and is freely available at:
      https://bitbucket.org/oruebel/brainformat.

PMID- 27867354
TI  - A Symmetry-Based Method to Infer Structural Brain Networks from Probabilistic
      Tractography Data.
AB  - Recent progress in diffusion MRI and tractography algorithms as well as the
      launch of the Human Connectome Project (HCP) have provided brain research with an
      abundance of structural connectivity data. In this work, we describe and evaluate
      a method that can infer the structural brain network that interconnects a given
      set of Regions of Interest (ROIs) from probabilistic tractography data. The
      proposed method, referred to as Minimum Asymmetry Network Inference Algorithm
      (MANIA), does not determine the connectivity between two ROIs based on an
      arbitrary connectivity threshold. Instead, we exploit a basic limitation of the
      tractography process: the observed streamlines from a source to a target do not
      provide any information about the polarity of the underlying white matter, and so
      if there are some fibers connecting two voxels (or two ROIs) X and Y,
      tractography should be able in principle to follow this connection in both
      directions, from X to Y and from Y to X. We leverage this limitation to formulate
      the network inference process as an optimization problem that minimizes the
      (appropriately normalized) asymmetry of the observed network. We evaluate the
      proposed method using both the FiberCup dataset and based on a noise model that
      randomly corrupts the observed connectivity of synthetic networks. As a case
      study, we apply MANIA on diffusion MRI data from 28 healthy subjects to infer the
      structural network between 18 corticolimbic ROIs that are associated with various
      neuropsychiatric conditions including depression, anxiety and addiction.

PMID- 27867356
TI  - Cyanidin-3-O-Glucoside Protects against 1,3-Dichloro-2-Propanol-Induced Reduction
      of Progesterone by Up-regulation of Steroidogenic Enzymes and cAMP Level in
      Leydig Cells.
AB  - 1,3-Dichloro-2-propanol (1,3-DCP) is a food processing contaminant and has been
      shown to perturb male reproductive function. Cyanidin-3-O-glucoside (C3G), an
      anthocyanin antioxidant, is reported to have protective effects on many organs.
      However, it remains unclear whether C3G protects against chemical-induced
      reproductive toxicity. The present study was therefore to investigate the
      intervention of C3G on 1,3-DCP-induced reproductive toxicity in R2C Leydig cells.
      Results demonstrated that C3G inhibited the 1,3-DCP-induced cytotoxicity and cell
      shape damage with the effective doses being ranging from 10 to 40 MUmol/L. In
      addition, 1,3-DCP (2 mmol/L) exposure significantly increased the ROS level and
      mitochondrial membrane potential damage ratio, leading to a decrease in
      progesterone production, while C3G intervention reduced the ROS level, and
      increased the progesterone production after 24 h treatment. Most importantly, C3G
      intervention could up-regulate the cyclic adenosine monophosphate (cAMP) level
      and protein expression of steroidogenic acute regulatory protein and 3beta
      hydroxysteroid dehydrogenase. It was concluded that C3G is effective in reducing
      1,3-DCP-induced reproductive toxicity via activating steroidogenic enzymes and
      cAMP level.

PMID- 27867357
TI  - Machine Perfusion of Porcine Livers with Oxygen-Carrying Solution Results in
      Reprogramming of Dynamic Inflammation Networks.
AB  - Background:Ex vivo machine perfusion (MP) can better preserve organs for
      transplantation. We have recently reported on the first application of an MP
      protocol in which liver allografts were fully oxygenated, under dual pressures
      and subnormothermic conditions, with a new hemoglobin-based oxygen carrier (HBOC)
      solution specifically developed for ex vivo utilization. In those studies, MP
      improved organ function post-operatively and reduced inflammation in porcine
      livers. Herein, we sought to refine our knowledge regarding the impact of MP by
      defining dynamic networks of inflammation in both tissue and perfusate. Methods:
      Porcine liver allografts were preserved either with MP (n = 6) or with cold
      static preservation (CSP; n = 6), then transplanted orthotopically after 9 h of
      preservation. Fourteen inflammatory mediators were measured in both tissue and
      perfusate during liver preservation at multiple time points, and analyzed using
      Dynamic Bayesian Network (DyBN) inference to define feedback interactions, as
      well as Dynamic Network Analysis (DyNA) to define the time-dependent development
      of inflammation networks. Results: Network analyses of tissue and perfusate
      suggested an NLRP3 inflammasome-regulated response in both treatment groups,
      driven by the pro-inflammatory cytokine interleukin (IL)-18 and the anti
      inflammatory mediator IL-1 receptor antagonist (IL-1RA). Both DyBN and DyNA
      suggested a reduced role of IL-18 and increased role of IL-1RA with MP, along
      with increased liver damage with CSP. DyNA also suggested divergent progression
      of responses over the 9 h preservation time, with CSP leading to a stable pattern
      of IL-18-induced liver damage and MP leading to a resolution of the pro
      inflammatory response. These results were consistent with prior clinical,
      biochemical, and histological findings after liver transplantation. Conclusion:
      Our results suggest that analysis of dynamic inflammation networks in the setting
      of liver preservation may identify novel diagnostic and therapeutic modalities.

PMID- 27867358
TI  - Biased Agonism of Three Different Cannabinoid Receptor Agonists in Mouse Brain
      Cortex.
AB  - Cannabinoid receptors are able to couple to different families of G proteins when
      activated by an agonist drug. It has been suggested that different intracellular
      responses may be activated depending on the ligand. The goal of the present study
      was to characterize the pattern of G protein subunit stimulation triggered by
      three different cannabinoid ligands, Delta9-THC, WIN55212-2, and ACEA in mouse
      brain cortex. Stimulation of the [35S]GTPgammaS binding coupled to specific
      immunoprecipitation with antibodies against different subtypes of G proteins
      (Galphai1, Galphai2, Galphai3, Galphao, Galphaz, Galphas, Galphaq/11, and
      Galpha12/13), in the presence of Delta9-THC, WIN55212-2 and ACEA (submaximal
      concentration 10 MUM) was determined by scintillation proximity assay (SPA)
      technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2
      double knock-out mice. Results show that, in mouse brain cortex, cannabinoid
      agonists are able to significantly stimulate not only the classical inhibitory
      Galphai/o subunits but also other G subunits like Galphaz, Galphaq/11, and
      Galpha12/13. Moreover, the specific pattern of G protein subunit activation is
      different depending on the ligand. In conclusion, our results demonstrate that,
      in mice brain native tissue, different exogenous cannabinoid ligands are able to
      selectively activate different inhibitory and non-inhibitory Galpha protein
      subtypes, through the activation of CB1 and/or CB2 receptors. Results of the
      present study may help to understand the specific molecular pathways involved in
      the pharmacological effects of cannabinoid-derived drugs.

PMID- 27867360
TI  - Inflammatory Cytokines and BDNF Response to High-Intensity Intermittent Exercise:
      Effect the Exercise Volume.
AB  - The purpose of this study was to compare the effects of two similar high
      intensity intermittent exercises (HIIE) but different volume 1.25 km (HIIE1.25)
      and 2.5 km (HIIE2.5) on inflammatory and BDNF responses. Ten physically active
      male subjects (age 25.22 +/- 1.74 years, body mass 78.98 +/- 7.31 kg, height 1.78
      +/- 0.06 m, VO2peak 59.94 +/- 9.38 ml.kg.min-1) performed an incremental
      treadmill exercise test and randomly completed two sessions of HIIE on a
      treadmill (1:1 min at vVO2max with passive recovery). Blood samples were
      collected at rest, immediately and 60-min after the exercise sessions. Serum was
      analyzed for glucose, lactate, IL-6, IL-10, and BDNF levels. Blood lactate
      concentrations was higher immediately post-exercise compared to rest (HIIE1.25:
      1.69 +/- 0.26-7.78 +/- 2.09 mmol.L-1, and HIIE2.5: 1.89 +/- 0.26-7.38 +/- 2.57
      mmol.L-1, p < 0.0001). Glucose concentrations did not present changes under the
      different conditions, however, levels were higher 60-min post-exercise than at
      rest only in the HIIE1.25 condition (rest: 76.80 +/- 11.14-97.84 +/- 24.87 mg.dL
      1, p < 0.05). BDNF level increased immediately after exercise in both protocols
      (HIIE1.25: 9.71 +/- 306-17.86 +/- 8.59 ng.mL-1, and HIIE2.5: 11.83 +/- 5.82-22.84
      +/- 10.30 ng.mL-1). Although both exercises increased IL-6, level percent between
      rest and immediately after exercise was higher in the HIIE2.5 than HIIE1.25 (30
      and 10%; p = 0.014, respectively). Moreover, IL-10 levels percent increase
      between immediately and 60-min post-exercise was higher in HIIE2.5 than HIIE1.25
      (37 and 10%; p = 0.012, respectively). In conclusion, both HIIE protocols with
      the same intensity were effective to increase BDNF and IL-6 levels immediately
      after exercise while only IL-10 response was related to the durantion of exercise
      indicanting the importance of this exercise prescription variable.

PMID- 27867361
TI  - Calcium-Sensing Receptor Regulates Cytosolic [Ca 2+ ] and Plays a Major Role in
      the Development of Pulmonary Hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease characterized by
      elevated pulmonary vascular resistance (PVR) leading to right heart failure and
      premature death. The increased PVR results in part from pulmonary vascular
      remodeling and sustained pulmonary vasoconstriction. Excessive pulmonary vascular
      remodeling stems from increased pulmonary arterial smooth muscle cell (PASMC)
      proliferation and decreased PASMC apoptosis. A rise in cytosolic free Ca2+
      concentration ([Ca2+]cyt) in PASMC is a major trigger for pulmonary
      vasoconstriction and a key stimulus for PASMC proliferation and migration, both
      contributing to the development of pulmonary vascular remodeling. PASMC from
      patients with idiopathic PAH (IPAH) have increased resting [Ca2+]cyt and enhanced
      Ca2+ influx. Enhanced Ca2+ entry into PASMC due to upregulation of membrane
      receptors and/or Ca2+ channels may contribute to PASMC contraction and
      proliferation and to pulmonary vasoconstriction and pulmonary vascular
      remodeling. We have shown that the extracellular Ca2+-sensing receptor (CaSR),
      which is a member of G protein-coupled receptor (GPCR) subfamily C, is
      upregulated, and the extracellular Ca2+-induced increase in [Ca2+]cyt is enhanced
      in PASMC from patients with IPAH in comparison to PASMC from normal subjects.
      Pharmacologically blockade of CaSR significantly attenuate the development and
      progression of experimental pulmonary hypertension in animals. Additionally, we
      have demonstrated that dihydropyridine Ca2+ channel blockers (e.g., nifedipine),
      which are used to treat PAH patients but are only effective in 15-20% of
      patients, activate CaSR resulting in an increase in [Ca2+]cyt in IPAH-PASMC, but
      not normal PASMC. Our data indicate that CaSR functionally couples with transient
      receptor potential canonical (TRPC) channels to mediate extracellular Ca2+
      induced Ca2+ influx and increase in [Ca2+]cyt in IPAH-PASMC. Upregulated CaSR is
      necessary for the enhanced extracellular Ca2+-induced increase in [Ca2+]cyt and
      the augmented proliferation of PASMC in patients with IPAH. This review will
      highlight the pathogenic role of CaSR in the development and progression of PAH.

PMID- 27867362
TI  - Association between Myocardial Infarction and Periodontitis: A Meta-Analysis of
      Case-Control Studies.
AB  - Background and Objective: Many clinical researches have been carried out to
      investigate the relationship between myocardial infarction (MI) and
      periodontitis. Despite most of them indicated that the periodontitis may be
      associated with an increased risk of MI, the findings and study types of these
      studies have been inconsistent. The goal of this meta-analysis was to critically
      assess the strength of the association between MI and periodontitis in case
      control studies. Methods: PubMed and the Cochrane Library were searched for
      eligible case-control studies reporting relevant parameters that compared
      periodontal status between MI and control subjects. The odds ratios (ORs) and 95%
      confidence intervals (CIs) from each study were pooled to estimate the strength
      of the association between MI and periodontitis. The mean differences and 95% CIs
      for periodontal-related parameters were calculated to determine their overall
      effects. Results: Seventeen studies including a total of 3456 MI patients and
      3875 non-MI control subjects were included. The pooled OR for the association
      between MI and periodontitis was 2.531 (95% CI: 1.927-3.324). The mean
      differences (95% CIs) for clinical attachment loss, probing depth, bleeding on
      probing, plaque index, and the number of missing teeth were 1.000 (0.726-1.247),
      1.209 (0.538-1.880), 0.342 (0.129-0.555), 0.383 (0.205-0.560), and 4.122 (2.012
      6.232), respectively. Conclusion: With the current evidence, the results support
      the presence of a significant association between MI and periodontitis. Moreover,
      MI patients had worse periodontal and oral hygiene status and fewer teeth than
      did control subjects. More high-quality and well-designed studies focusing on the
      casual relationship between MI and periodontitis should be conducted in the
      future.

PMID- 27867359
TI  - Physiology and Evolution of Voltage-Gated Calcium Channels in Early Diverging
      Animal Phyla: Cnidaria, Placozoa, Porifera and Ctenophora.
AB  - Voltage-gated calcium (Cav) channels serve dual roles in the cell, where they can
      both depolarize the membrane potential for electrical excitability, and activate
      transient cytoplasmic Ca2+ signals. In animals, Cav channels play crucial roles
      including driving muscle contraction (excitation-contraction coupling), gene
      expression (excitation-transcription coupling), pre-synaptic and neuroendocrine
      exocytosis (excitation-secretion coupling), regulation of flagellar/ciliary
      beating, and regulation of cellular excitability, either directly or through
      modulation of other Ca2+-sensitive ion channels. In recent years, genome
      sequencing has provided significant insights into the molecular evolution of Cav
      channels. Furthermore, expanded gene datasets have permitted improved inference
      of the species phylogeny at the base of Metazoa, providing clearer insights into
      the evolution of complex animal traits which involve Cav channels, including the
      nervous system. For the various types of metazoan Cav channels, key properties
      that determine their cellular contribution include: Ion selectivity, pore gating,
      and, importantly, cytoplasmic protein-protein interactions that direct sub
      cellular localization and functional complexing. It is unclear when these
      defining features, many of which are essential for nervous system function,
      evolved. In this review, we highlight some experimental observations that
      implicate Cav channels in the physiology and behavior of the most early-diverging
      animals from the phyla Cnidaria, Placozoa, Porifera, and Ctenophora. Given our
      limited understanding of the molecular biology of Cav channels in these basal
      animal lineages, we infer insights from better-studied vertebrate and
      invertebrate animals. We also highlight some apparently conserved cellular
      functions of Cav channels, which might have emerged very early on during metazoan
      evolution, or perhaps predated it.

PMID- 27867364
TI  - An Objective Screening Method for Major Depressive Disorder Using Logistic
      Regression Analysis of Heart Rate Variability Data Obtained in a Mental Task
      Paradigm.
AB  - BACKGROUND AND OBJECTIVES: Heart rate variability (HRV) has been intensively
      studied as a promising biological marker of major depressive disorder (MDD). Our
      previous study confirmed that autonomic activity and reactivity in depression
      revealed by HRV during rest and mental task (MT) conditions can be used as
      diagnostic measures and in clinical evaluation. In this study, logistic
      regression analysis (LRA) was utilized for the classification and prediction of
      MDD based on HRV data obtained in an MT paradigm. METHODS: Power spectral
      analysis of HRV on R-R intervals before, during, and after an MT (random number
      generation) was performed in 44 drug-naive patients with MDD and 47 healthy
      control subjects at Department of Psychiatry in Shizuoka Saiseikai General
      Hospital. Logit scores of LRA determined by HRV indices and heart rates
      discriminated patients with MDD from healthy subjects. The high frequency (HF)
      component of HRV and the ratio of the low frequency (LF) component to the HF
      component (LF/HF) correspond to parasympathetic and sympathovagal balance,
      respectively. RESULTS: The LRA achieved a sensitivity and specificity of 80.0 and
      79.0%, respectively, at an optimum cutoff logit score (0.28). Misclassifications
      occurred only when the logit score was close to the cutoff score. Logit scores
      also correlated significantly with subjective self-rating depression scale scores
      (p < 0.05). CONCLUSION: HRV indices recorded during a MT may be an objective tool
      for screening patients with MDD in psychiatric practice. The proposed method
      appears promising for not only objective and rapid MDD screening but also
      evaluation of its severity.

PMID- 27867363
TI  - A Comparative Review of microRNA Expression Patterns in Autism Spectrum Disorder.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by
      a wide spectrum of deficits in social interaction, communication, and behavior.
      There is a significant genetic component to ASD, yet no single gene variant
      accounts for >1% of incidence. Posttranscriptional mechanisms such as microRNAs
      (miRNAs) regulate gene expression without altering the genetic code. They are
      abundant in the developing brain and are dysregulated in children with ASD.
      Patterns of miRNA expression are altered in the brain, blood, saliva, and
      olfactory precursor cells of ASD subjects. The ability of miRNAs to regulate
      broad molecular pathways in response to environmental stimuli makes them an
      intriguing player in ASD, a disorder characterized by genetic predisposition with
      ill-defined environmental triggers. In addition, the availability and
      extracellular stability of miRNAs make them an ideal candidate for biomarker
      discovery. Here, we discuss 27 miRNAs with overlap across ASD studies, including
      3 miRNAs identified in 3 or more studies (miR-23a, miR-146a, and miR-106b).
      Together, these 27 miRNAs have 1245 high-confidence mRNA targets, a significant
      number of which are expressed in the brain. Furthermore, these mRNA targets
      demonstrate over-representation of autism-related genes with enrichment of
      neurotrophic signaling molecules. Brain-derived neurotrophic factor, a molecule
      involved in hippocampal neurogenesis and altered in ASD, is targeted by 6 of the
      27 miRNAs of interest. This neurotrophic pathway represents one intriguing
      mechanism by which perturbations in miRNA signaling might influence central
      nervous system development in children with ASD.

PMID- 27867365
TI  - Gender Agreement Attraction in Russian: Production and Comprehension Evidence.
AB  - Agreement attraction errors (such as the number error in the example "The key to
      the cabinets are rusty") have been the object of many studies in the last 20
      years. So far, almost all production experiments and all comprehension
      experiments looked at binary features (primarily at number in Germanic, Romance,
      and some other languages, in several cases at gender in Romance languages). Among
      other things, it was noted that both in production and in comprehension,
      attraction effects are much stronger for some feature combinations than for the
      others: they can be observed in the sentences with singular heads and plural
      dependent nouns (e.g.,"The key to the cabinets..."), but not in the sentences
      with plural heads and singular dependent nouns (e.g., "The keys to the
      cabinet..."). Almost all proposed explanations of this asymmetry appeal to
      feature markedness, but existing findings do not allow teasing different
      approaches to markedness apart. We report the results of four experiments (one on
      production and three on comprehension) studying subject-verb gender agreement in
      Russian, a language with three genders. Firstly, we found attraction effects both
      in production and in comprehension, but, unlike in the case of number agreement,
      they were not parallel (in production, feminine gender triggered strongest
      effects, while neuter triggered weakest effects, while in comprehension,
      masculine triggered weakest effects). Secondly, in the comprehension experiments
      attraction was observed for all dependent noun genders, but only for a subset of
      head noun genders. This goes against the traditional assumption that the features
      of the dependent noun are crucial for attraction, showing the features of the
      head are more important. We demonstrate that this approach can be extended to
      previous findings on attraction and that there exists other evidence for it. In
      total, these findings let us reconsider the question which properties of features
      are crucial for agreement attraction in production and in comprehension.

PMID- 27867366
TI  - The Impact of Perspective Change As a Cognitive Reappraisal Strategy on Affect: A
      Systematic Review.
AB  - The strategic or deliberate adoption of a cognitively distanced, third-person
      perspective is proposed to adaptively regulate emotions. However, studies of
      psychological disorders suggest spontaneous adoption of a third-person
      perspective reflects counter-productive avoidance. Here, we review studies that
      investigate the deliberate adoption of a third- or first-person vantage
      perspective and its impact on affect in healthy people, "sub-clinical"
      populations and those with psychological disorders. A systematic search was
      conducted across four databases. After exclusion criteria were applied, 38
      studies were identified that investigated the impact of both imagery and verbal
      instructions designed to encourage adoption of a third-person perspective on self
      reported affect. The identified studies examined a variety of outcomes related to
      recalling memories, imagining scenarios and mood induction. These were associated
      with specific negative emotions or mood states (dysphoria/sadness, anxiety,
      anger), mixed or neutral affect autobiographical memories, and self-conscious
      affect (e.g., guilt). Engaging a third-person perspective was generally
      associated with a reduction in the intensity of positive and negative affect.
      Studies that included measures of semantic change, suggested that this is a key
      mediator in reduction of affect following perspective change. Strategically
      adopting a "distanced," third-person perspective is linked to a reduction in
      affect intensity across valence, but in addition has the potential to introduce
      new information that regulates emotion via semantic change. Such reappraisal
      distinguishes deliberate adoption of a distanced perspective from the habitual
      and/or spontaneous shift in perspective that occurs in psychopathology.

PMID- 27867367
TI  - Mentalizing and Information Propagation through Social Network: Evidence from a
      Resting-State-fMRI Study.
AB  - Microblogs is one of the main social networking channels by which information is
      spread. Among them, Sina Weibo is one of the largest social networking channels
      in China. Millions of users repost information from Sina Weibo and share embedded
      emotion at the same time. The present study investigated participants' propensity
      to repost microblog messages of positive, negative, or neutral valence, and
      studied the neural correlates during resting state with the reposting rate of
      each type microblog messages. Participants preferred to repost negative messages
      relative to positive and neutral messages. Reposting rate of negative messages
      was positively correlated to the functional connectivity of temporoparietal
      junction (TPJ) with insula, and TPJ with dorsolateral prefrontal cortex. These
      results indicate that reposting negative messages is related to conflict
      resolution between the feeling of pain/disgust and the intention to repost
      significant information. Thus, resposting emotional microblog messages might be
      attributed to participants' appraisal of personal and recipient's interest, as
      well as their cognitive process for decision making.

PMID- 27867368
TI  - How do Co-agents Actively Regulate their Collective Behavior States?

PMID- 27867369
TI  - Formal Semantics in the Neurology Clinic: Atypical Understanding of Aspectual
      Coercion in ALS Patients.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor
      system with subtle adverse effects on cognition. It is still unclear whether ALS
      also affects language and semantics, and if so, what aspects and processes
      exactly. We investigated how ALS patients understand verb phrases modified by
      temporal preposition phrases, e.g., "To watch TV for half an hour."
      Interpretation here requires operations such as aspectual coercion that add or
      delete elements from event structures, depending on temporal modifiers, and
      constraints on coercion, which make combinations with certain modifiers not
      viable. Using a theoretically-motivated experimental design, we observed that
      acceptance rates for aspectual coercion were abnormally high in ALS patients. The
      effect was largest for the more complex cases of coercion: not those that involve
      enrichment of event structures ("To switch on the TV in half an hour," where a
      number of failed attempts must be included in the interpretation) but those that,
      if applied, would result in deletion of event structure elements ("To repair the
      TV for half an hour"). Our experimental results are consistent with a deficit of
      constraints on coercion, and not with impaired semantic processes or
      representations, in line with recent studies suggesting that verb semantics is
      largely spared in ALS.

PMID- 27867370
TI  - Theory of Mind Deficits and Social Emotional Functioning in Preschoolers with
      Specific Language Impairment.
AB  - Children with Specific Language Impairment (SLI) often experience emotional and
      social difficulties. In general, problems in social emotional functioning can be
      cognitively explained in terms of Theory of Mind (ToM). In this mini-review, an
      overview is provided of studies on social-emotional functioning and ToM in
      preschoolers (average age from 2.3 to 6.2 years) with SLI. It is concluded that,
      similar to school-aged children with SLI, preschoolers with SLI have several
      social-emotional problems and that both cognitive and affective aspects of ToM
      are impaired in those children. Based hereon, three possible causal models for
      the interrelation between language, ToM and social emotional functioning are put
      forward. It is proposed that future research on the construct and measurement of
      early ToM, social emotional functioning and language development in preschoolers
      with SLI is needed to achieve early detection, tailored treatment, and ultimately
      insight into the pathogenesis of SLI.

PMID- 27867371
TI  - "Candidatus Gortzia shahrazadis", a Novel Endosymbiont of Paramecium
      multimicronucleatum and a Revision of the Biogeographical Distribution of
      Holospora-Like Bacteria.
AB  - Holospora spp. and "Candidatus Gortzia infectiva", known as Holospora-like
      bacteria (HLB), are commonly found as nuclear endosymbionts of ciliates,
      especially the Paramecium genus. HLB are related by phylogenetic relationships,
      morphological features, and life-cycles, which involve two alternating
      morphotypes: reproductive and infectious forms (RF, IF). In this paper we
      describe a novel species belonging to the "Ca. Gortzia" genus, detected in P.
      multimicronucleatum, a ciliate for which infection by an HLB has not been
      reported, discovered in India. This novel endosymbiont shows unusual and
      surprising features with respect to other HLB, such as large variations in IF
      morphology and the occasional ability to reproduce in the host cytoplasm. We
      propose the name of "Candidatus Gortzia shahrazadis" for this novel HLB.
      Moreover, we report two additional species of HLB from Indian Paramecium
      populations: "Ca. Gortzia infectiva" (from P. jenningsi), and H. obtusa (from P.
      caudatum); the latter is the first record of Holospora from a tropical country.
      Although tropical, we retrieved H. obtusa at an elevation of 706 m corresponding
      to a moderate climate not unlike conditions where Holospora are normally found,
      suggesting the genus Holospora does exist in tropical countries, but restricted
      to higher elevations.

PMID- 27867372
TI  - Overlapping Regions in HIV-1 Genome Act as Potential Sites for Host-Virus
      Interaction.
AB  - More than a decade, overlapping genes in RNA viruses became a subject of research
      which has explored various effect of gene overlapping on the evolution and
      function of viral genomes like genome size compaction. Additionally, overlapping
      regions (OVRs) are also reported to encode elevated degree of protein intrinsic
      disorder (PID) in unspliced RNA viruses. With the aim to explore the roles of
      OVRs in HIV-1 pathogenesis, we have carried out an in-depth analysis on the
      association of gene overlapping with PID in 35 HIV1- M subtypes. Our study
      reveals an over representation of PID in OVR of HIV-1 genomes. These disordered
      residues endure several vital, structural features like short linear motifs
      (SLiMs) and protein phosphorylation (PP) sites which are previously shown to be
      involved in massive host-virus interaction. Moreover, SLiMs in OVRs are noticed
      to be more functionally potential as compared to that of non-overlapping region.
      Although, density of experimentally verified SLiMs, resided in 9 HIV-1 genes,
      involved in host-virus interaction do not show any bias toward clustering into
      OVR, tat and rev two important proteins mediates host-pathogen interaction by
      their experimentally verified SLiMs, which are mostly localized in OVR. Finally,
      our analysis suggests that the acquisition of SLiMs in OVR is mutually exclusive
      of the occurrence of disordered residues, while the enrichment of PPs in OVR is
      solely dependent on PID and not on overlapping coding frames. Thus, OVRs of HIV-1
      genomes could be demarcated as potential molecular recognition sites during host
      virus interaction.

PMID- 27867374
TI  - Editorial: Proteomics of Microbial Human Pathogens.

PMID- 27867373
TI  - Two Genetically Similar H9N2 Influenza A Viruses Show Different Pathogenicity in
      Mice.
AB  - H9N2 Avian influenza virus has repeatedly infected humans and other mammals,
      which highlights the need to determine the pathogenicity and the corresponding
      mechanism of this virus for mammals. In this study, we found two H9N2 viruses
      with similar genetic background but with different pathogenicity in mice. The
      A/duck/Nanjing/06/2003 (NJ06) virus was highly pathogenic for mice, with a 50%
      mouse lethal dose (MLD50) of 102.83 50% egg infectious dose (EID50), whereas the
      A/duck/Nanjing/01/1999 (NJ01) virus was low pathogenic for mice, with a MLD50 of
      >106.81 EID50. Further studies showed that the NJ06 virus grew faster and reached
      significantly higher titers than NJ01 in vivo and in vitro. Moreover, the NJ06
      virus induced more severe lung lesions, and higher levels of inflammatory
      cellular infiltration and cytokine response in lungs than NJ01 did. However, only
      12 different amino acid residues (HA-K157E, NA-A9T, NA-R435K, PB2-T149P, PB2
      K627E, PB1-R187K, PA-L548M, PA-M550L, NP-G127E, NP-P277H, NP-D340N, NS1-D171N)
      were found between the two viruses, and all these residues except for NA-R435K
      were located in the known functional regions involved in interaction of viral
      proteins or between the virus and host factors. Summary, our results suggest that
      multiple amino acid differences may be responsible for the higher pathogenicity
      of the NJ06 virus for mice, resulting in lethal infection, enhanced viral
      replication, severe lung lesions, and excessive inflammatory cellular
      infiltration and cytokine response in lungs. These observations will be helpful
      for better understanding the pathogenic potential and the corresponding molecular
      basis of H9N2 viruses that might pose threats to human health in the future.

PMID- 27867375
TI  - Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-Like Microcolony B.
      burgdorferi Persisters Which Are Sterilized by Daptomycin/ Doxycycline/Cefuroxime
      without Pulse Dosing.
AB  - Although the majority of Lyme disease patients can be cured, at least 10-20% of
      the patients continue to suffer from persisting symptoms such as fatigue,
      muscular and joint pain, and neurologic impairment after standard 2-4 week
      antibiotic treatment. While the causes for this post-treatment Lyme disease
      symptoms are unclear, one possibility is due to Borrelia burgdorferi persisters
      that are not effectively killed by current antibiotics such as doxycycline or
      amoxicillin used to treat Lyme disease. A previous study showed that four rounds
      of ceftriaxone pulse dosing treatment eradicated B. burgdorferi persisters in
      vitro using a relatively young late log phase culture (5 day old). In this study,
      we investigated if ceftriaxone pulse dosing could also eradicate B. burgdorferi
      persisters in older stationary phase cultures (10 day old) enriched with more
      resistant microcolony form of persisters. We found that ceftriaxone pulse dosing
      could only eradicate planktonic log phase B. burgdorferi spirochetal forms and
      round body forms but not more resistant aggregated biofilm-like microcolony
      persisters enriched in stationary phase cultures. Moreover, we found that not all
      drugs are suitable for pulse dosing, with bactericidal drugs ceftriaxone and
      cefuroxime being more appropriate for pulse dosing than bacteriostatic drug
      doxycycline and persister drug daptomycin. We also showed that drug combination
      pulse dosing treatment was more effective than single drug pulse dosing.
      Importantly, we demonstrate that pulse dosing treatment impaired the activity of
      the persister drug daptomycin and its drug combination against B. burgdorferi
      persisters and that the most effective way to kill the more resistant biofilm
      like microcolonies is the daptomycin/doxycycline/ceftriaxone triple drug
      combination without pulse dosing. Our findings indicate pulse dosing may not
      always work as a general principle but rather depends on the specific drugs used,
      with cidal drugs being more appropriate for pulse dosing than static or persister
      drugs, and that drug combination approach with persister drugs is more effective
      at killing the more resistant microcolony form of persisters than pulse dosing.
      These observations may have implications for more effective treatment of Lyme
      disease. Future studies are required to validate these findings in animal models
      of B. burgdorferi persistence.

PMID- 27867376
TI  - The Exosporium of Bacillus megaterium QM B1551 Is Permeable to the Red
      Fluorescence Protein of the Coral Discosoma sp.
AB  - Bacterial spores spontaneously interact and tightly bind heterologous proteins. A
      variety of antigens and enzymes have been efficiently displayed on spores of
      Bacillus subtilis, the model system for spore formers. Adsorption on B. subtilis
      spores has then been proposed as a non-recombinant approach for the development
      of mucosal vaccine/drug delivery vehicles, biocatalysts, bioremediation, and
      diagnostic tools. We used spores of B. megaterium QM B1551 to evaluate their
      efficiency as an adsorption platform. Spores of B. megaterium are significantly
      larger than those of B. subtilis and of other Bacillus species and are surrounded
      by the exosporium, an outermost surface layer present only in some Bacillus
      species and lacking in B. subtilis. Strain QM B1551 of B. megaterium and a
      derivative strain totally lacking the exosporium were used to localize the
      adsorbed monomeric Red Fluorescent Protein (mRFP) of the coral Discosoma sp.,
      used as a model heterologous protein. Our results indicate that spores of B.
      megaterium adsorb mRFP more efficiently than B. subtilis spores, that the
      exosporium is essential for mRFP adsorption, and that most of the adsorbed mRFP
      molecules are not exposed on the spore surface but rather localized in the space
      between the outer coat and the exosporium.

PMID- 27867377
TI  - Over-Expression of the Mycobacterial Trehalose-Phosphate Phosphatase OtsB2
      Results in a Defect in Macrophage Phagocytosis Associated with Increased
      Mycobacterial-Macrophage Adhesion.
AB  - Trehalose-6-phosphate phosphatase (OtsB2) is involved in the OtsAB trehalose
      synthesis pathway to produce free trehalose and is strictly essential for
      mycobacterial growth. We wished to determine the effects of OtsB2 expression on
      mycobacterial phenotypes such as growth, phagocytosis and survival in
      macrophages. Mycobacterium bovis-bacillus calmette-guerin (BCG) over-expressing
      OtsB2 were able to better survive in stationary phase. Over-expression of OtsB2
      led to a decrease in phagocytosis but not survival in THP-1 macrophage-like
      cells, and this was not due to a decrease in general macrophage phagocytic
      activity. Surprisingly, when we investigated macrophage-mycobacterial
      interactions by flow cytometry and atomic force microscopy, we discovered that
      BCG over-expressing OtsB2 have stronger binding to THP-1 cells than wild-type
      BCG. These results suggest that altering OtsB2 expression has implications for
      mycobacterial host-pathogen interactions. Macrophage-mycobacteria phagocytic
      interactions are complex and merit further study.

PMID- 27867378
TI  - Improved Pathogenicity of a Beet Black Scorch Virus Variant by Low Temperature
      and Co-infection with Its Satellite RNA.
AB  - Co-infection of none-coding satellite RNAs (sat-RNAs) usually inhibits
      replication and attenuates disease symptoms of helper viruses. However, we find
      that the sat-RNA of Beet black scorch virus (BBSV) and low temperature (18
      degrees C) additively enhance the systemic infection of BBSV in Nicotiana
      benthamiana. Northern blotting hybridization revealed a relatively reduced
      accumulation of BBSV-derived small interfering RNAs (siRNAs) in presence of sat
      RNA as compared to that of BBSV alone. Cloning and sequencing of total small RNAs
      showed that more than 50% of the total small RNAs sequenced from BBSV-infected
      plants were BBSV-siRNAs, whereas the abundance of sat-siRNAs were higher than
      BBSV-siRNAs in the sat-RNA co-infected plants, indicating that the sat-RNA
      occupies most of the silencing components and possibly relieves the RNA silencing
      mediated defense against BBSV. Interestingly, the 5' termini of siRNAs derived
      from BBSV and sat-RNA were dominated by Uridines (U) and Adenines (A),
      respectively. Besides, the infection of BBSV alone and with sat-RNA induce down
      regulation of miR168 and miR403, respectively, which leads to high accumulation
      of their targets, Argonaute 1 (AGO1) and AGO2. Our work reveals the profiles of
      siRNAs of BBSV and sat-RNA and provides an additional clue to investigate the
      complicated interaction between the helper virus and sat-RNA.

PMID- 27867380
TI  - IMPre: An Accurate and Efficient Software for Prediction of T- and B-Cell
      Receptor Germline Genes and Alleles from Rearranged Repertoire Data.
AB  - Large-scale study of the properties of T-cell receptor (TCR) and B-cell receptor
      (BCR) repertoires through next-generation sequencing is providing excellent
      insights into the understanding of adaptive immune responses.
      Variable(Diversity)Joining [V(D)J] germline genes and alleles must be
      characterized in detail to facilitate repertoire analyses. However, most species
      do not have well-characterized TCR/BCR germline genes because of their high
      homology. Also, more germline alleles are required for humans and other species,
      which limits the capacity for studying immune repertoires. Herein, we developed
      "Immune Germline Prediction" (IMPre), a tool for predicting germline V/J genes
      and alleles using deep-sequencing data derived from TCR/BCR repertoires. We
      developed a new algorithm, "Seed_Clust," for clustering, produced a multiway tree
      for assembly and optimized the sequence according to the characteristics of
      rearrangement. We trained IMPre on human samples of T-cell receptor beta (TRB)
      and immunoglobulin heavy chain and then tested it on additional human samples.
      Accuracy of 97.7, 100, 92.9, and 100% was obtained for TRBV, TRBJ, IGHV, and
      IGHJ, respectively. Analyses of subsampling performance for these samples showed
      IMPre to be robust using different data quantities. Subsequently, IMPre was
      tested on samples from rhesus monkeys and human long sequences: the highly
      accurate results demonstrated IMPre to be stable with animal and multiple data
      types. With rapid accumulation of high-throughput sequence data for TCR and BCR
      repertoires, IMPre can be applied broadly for obtaining novel genes and a large
      number of novel alleles. IMPre is available at
      https://github.com/zhangwei2015/IMPre.

PMID- 27867379
TI  - Convergence of Innate and Adaptive Immunity during Human Aging.
AB  - Aging is associated with profound changes in the human immune system, a
      phenomenon referred to as immunosenescence. This complex immune remodeling
      affects the adaptive immune system and the CD8+ T cell compartment in particular,
      leading to the accumulation of terminally differentiated T cells, which can
      rapidly exert their effector functions at the expenses of a limited proliferative
      potential. In this review, we will discuss evidence suggesting that senescent
      alphabetaCD8+ T cells acquire the hallmarks of innate-like T cells and use
      recently acquired NK cell receptors as an alternative mechanism to mediate rapid
      effector functions. These cells concomitantly lose expression of co-stimulatory
      receptors and exhibit decreased T cell receptor signaling, suggesting a
      functional shift away from antigen-specific activation. The convergence of innate
      and adaptive features in senescent T cells challenges the classic division
      between innate and adaptive immune systems. Innate-like T cells are particularly
      important for stress and tumor surveillance, and we propose a new role for these
      cells in aging, where the acquisition of innate-like functions may represent a
      beneficial adaptation to an increased burden of malignancy with age, although it
      may also pose a higher risk of autoimmune disorders.

PMID- 27867384
TI  - Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates
      with Active Visceral Disease in Humans.
AB  - The complexity of Leishmania-host interactions, one of the main leishmaniasis
      issues, is yet to be fully understood. We detected elevated IL-27 plasma levels
      in European patients with active visceral disease caused by Leishmania infantum,
      which returned to basal levels after successful treatment, suggesting this
      cytokine as a probable infection mediator. We further addressed this hypothesis
      recurring to two classical susceptible visceral leishmaniasis mouse models.
      BALB/c, but not C57BL/6 mice, showed increased IL-27 systemic levels after
      infection, which was associated with an upregulation of IL-27p28 expression by
      dendritic cells and higher parasite burdens. Neutralization of IL-27 in acutely
      infected BALB/c led to decreased parasite burdens and a transient increase in IFN
      gamma+ splenic T cells, while administration of IL-27 to C57BL/6 promoted a local
      anti-inflammatory cytokine response at the site of infection and increased
      parasite loads. Overall, we show that, as in humans, BALB/c IL-27 systemic levels
      are infection dependently upregulated and may favor parasite installation by
      controlling inflammation.

PMID- 27867381
TI  - A Critical Reappraisal of Neutrophil Extracellular Traps and NETosis Mimics Based
      on Differential Requirements for Protein Citrullination.
AB  - NETosis, an antimicrobial form of neutrophil cell death, is considered a primary
      source of citrullinated autoantigens in rheumatoid arthritis (RA) and immunogenic
      DNA in systemic lupus erythematosus (SLE). Activation of the citrullinating
      enzyme peptidylarginine deiminase type 4 (PAD4) is believed to be essential for
      neutrophil extracellular trap (NET) formation and NETosis. PAD4 is therefore
      viewed as a promising therapeutic target to inhibit the formation of NETs in both
      diseases. In this review, we examine the evidence for PAD4 activation during
      NETosis and provide experimental data to suggest that protein citrullination is
      not a universal feature of NETs. We delineate two distinct biological processes,
      leukotoxic hypercitrullination (LTH) and defective mitophagy, which have been
      erroneously classified as "NETosis." While these NETosis mimics share
      morphological similarities with NETosis (i.e., extracellular DNA release), they
      are biologically distinct. As such, these processes can be readily classified by
      their stimuli, activation of distinct biochemical pathways, the presence of
      hypercitrullination, and antimicrobial effector function. NETosis is an
      antimicrobial form of cell death that is NADPH oxidase-dependent and not
      associated with hypercitrullination. In contrast, LTH is NADPH oxidase
      independent and not bactericidal. Rather, LTH represents a bacterial strategy to
      achieve immune evasion. It is triggered by pore-forming pathways and equivalent
      signals that cumulate in calcium-dependent hyperactivation of PADs, protein
      hypercitrullination, and neutrophil death. The generation of citrullinated
      autoantigens in RA is likely driven by LTH, but not NETosis. Mitochondrial DNA
      (mtDNA) expulsion, the result of a constitutive defect in mitophagy, represents a
      second NETosis mimic. In the presence of interferon-alpha and immune complexes,
      this process can generate highly interferogenic oxidized mtDNA, which has
      previously been mistaken for NETosis in SLE. Distinguishing NETosis from LTH and
      defective mitophagy is paramount to understanding the role of neutrophil damage
      in immunity and the pathogenesis of human diseases. This provides a framework to
      design specific inhibitors of these distinct biological processes in human
      disease.

PMID- 27867382
TI  - IL-1beta, But Not Programed Death-1 and Programed Death Ligand Pathway, Is
      Critical for the Human Th17 Response to Mycobacterium tuberculosis.
AB  - The programed death-1 (PD-1)-programed death ligand-1 (PD-L1) and PD-L2 co
      inhibitory pathway has been implicated in the evasion strategies of Mycobacterium
      tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion
      of regulatory T cells and suppression of Th1 response. However, the role of PD
      pathway in regulating Th17 response to M. tuberculosis has not been investigated.
      In the present report, we demonstrate that M. tuberculosis and M. tuberculosis
      derived antigen fractions have differential abilities to mediate human monocyte-
      and dendritic cell (DC)-mediated Th17 response and were independent of expression
      of PD-L1 or PD-L2 on aforementioned antigen-presenting cells. Importantly, we
      observed that blockade of PD-L1 or PD-1 did not significantly modify either the
      frequencies of Th17 cells or the production of IL-17 from CD4+ T cells though IFN
      gamma response was significantly enhanced. On the contrary, IL-1beta from
      monocytes and DCs were critical for the Th17 response to M. tuberculosis.
      Together, our results indicate that IL-1beta, but not members of the programed
      death pathway, is critical for human Th17 response to M. tuberculosis.

PMID- 27867383
TI  - Environmental Toxicants-Induced Immune Responses in the Olfactory Mucosa.
AB  - Olfactory sensory neurons (OSNs) are the receptor cells for the sense of smell.
      Although cell bodies are located in the olfactory mucosa (OM) of the nasal
      cavity, OSN axons directly project to the olfactory bulb (OB) that is a component
      of the central nervous system (CNS). Because of this direct and short connection
      from this peripheral tissue to the CNS, the olfactory system has attracted
      attention as a port-of-entry for environmental toxicants that may cause
      neurological dysfunction. Selected viruses can enter the OB via the OM and
      directly affect the CNS. On the other hand, environmental toxicants may induce
      inflammatory responses in the OM, including infiltration of immune cells and
      production of inflammatory cytokines. In addition, these inflammatory responses
      cause the loss of OSNs that are then replaced with newly generated OSNs that re
      connect to the OB after inflammation has subsided. It is now known that immune
      cells and cytokines in the OM play important roles in both degeneration and
      regeneration of OSNs. Thus, the olfactory system is a unique neuroimmune
      interface where interaction between nervous and immune systems in the periphery
      significantly affects the structure, neuronal circuitry, and immunological status
      of the CNS. The mechanisms by which immune cells regulate OSN loss and the
      generation of new OSNs are, however, largely unknown. To help develop a better
      understanding of the mechanisms involved, we have provided a review of key
      research that has investigated how the immune response in the OM affects the
      pathophysiology of OSNs.

PMID- 27867385
TI  - Expanding Diversity in Molecular Structures and Functions of the IL-6/IL-12
      Heterodimeric Cytokine Family.
AB  - The interleukin (IL)-6/IL-12 family cytokines have pleiotropic functions and play
      critical roles in multiple immune responses. This cytokine family has very unique
      characteristics in that they comprise two distinct subunits forming a heterodimer
      and each cytokine and receptor subunit shares with each other. The members of
      this cytokine family are increasing; currently, there are more than six
      cytokines, including the tentatively named cytokines IL-Y (p28/p40), IL-12
      (p35/p40), IL-23 (p19/p40), IL-27 [p28/Epstein-Barr virus-induced protein 3
      (EBI3)], IL-35 (p35/EBI3), and IL-39 (p19/EBI3). This family of cytokines covers
      a very broad range of immune responses, including pro-inflammatory responses,
      such as helper T (Th)1, Th2, and Th17, to anti-inflammatory responses, such as
      regulatory T (Treg) cells and IL-10-producing Treg cells. IL-12 is the first
      member of this family, and IL-12, IL-23, and IL-27 are mainly produced by
      activated antigen-presenting cells, such as dendritic cells and macrophages. IL
      12 plays a critical role in the promotion of Th1 immune responses by inducing
      interferon-gamma production to combat pathogens and malignant tumors. IL-23
      induces IL-17 production and is necessary to maintain pathogenic Th17 cells that
      cause inflammatory and autoimmune diseases. IL-27 was initially reported to play
      a critical role in promotion of Th1 differentiation; however, subsequent studies
      revealed that IL-27 has broader stimulatory and inhibitory roles by inducing IL
      10-producing Treg cells. IL-35 is produced by forkhead box P3+ Treg cells and
      activated B cells and has immunosuppressive functions to maintain immune
      tolerance. The most recently identified cytokine, IL-39, is produced by activated
      B cells and has pro-inflammatory functions. The cytokine tentatively named IL-Y
      seems to have anti-inflammatory functions by inhibiting Th1 and Th17
      differentiation. In addition, individual cytokine subunits were also shown to
      have self-standing activities. Thus, promiscuity within the IL-6/IL-12 family
      cytokines complicates structural and functional clarification and assignment of
      individual cytokines. A better understanding of the recent advances and expanding
      diversity in molecular structures and functions of the IL-6/IL-12 family
      cytokines could allow the creation of novel therapeutic strategies by using them
      as tools and targeted molecules.

PMID- 27867386
TI  - Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity.
AB  - Pericytes (PC) are mural cells that surround endothelial cells in small blood
      vessels. PC have traditionally been credited with structural functions, being
      essential for vessel maturation and stabilization. However, an accumulating body
      of evidence suggests that PC also display immune properties. They can respond to
      a series of pro-inflammatory stimuli and are able to sense different types of
      danger due to their expression of functional pattern-recognition receptors,
      contributing to the onset of innate immune responses. In this context, PC not
      only secrete a variety of chemokines but also overexpress adhesion molecules such
      as ICAM-1 and VCAM-1 involved in the control of immune cell trafficking across
      vessel walls. In addition to their role in innate immunity, PC are involved in
      adaptive immunity. It has been reported that interaction with PC anergizes T
      cells, which is attributed, at least in part, to the expression of PD-L1. As
      components of the tumor microenvironment, PC can also modulate the antitumor
      immune response. However, their role is complex, and further studies will be
      required to better understand the crosstalk of PC with immune cells in order to
      consider them as potential therapeutic targets. In any case, PC will be looked at
      with new eyes by immunologists from now on.

PMID- 27867387
TI  - Neutrophils Discriminate between Lipopolysaccharides of Different Bacterial
      Sources and Selectively Release Neutrophil Extracellular Traps.
AB  - The release of neutrophil extracellular traps (NETs), either during "suicidal" or
      "vital" NETosis, represents an important strategy of neutrophils to combat Gram
      negative bacteria. Lipopolysaccharide (LPS), a major component of the outer
      membrane of Gram-negative bacteria, is a reported stimulus for NET formation.
      Although it is widely acknowledged that the structural diversity in LPS
      structures can elicit heterogeneous immune responses, species- and serotype
      specific differences in the capacity of LPS to trigger NET formation have not yet
      been investigated. In the present study, we compared the NET-inducing potential
      of LPS derived from Escherichia coli (serotypes O55:B5, O127:B8, O128:B12,
      O111:B4, and O26:B6), Salmonella enterica (serotype enteritidis), and Pseudomonas
      aeruginosa (serotype 10), under platelet-free and platelet-rich conditions in
      vitro, and in whole blood ex vivo. Here, we demonstrate that under serum- and
      platelet-free conditions, mimicking tissue circumstances, neutrophils
      discriminate between LPS of different bacterial sources and selectively release
      NETs only in response to LPS derived from E. coli O128:B12 and P. aeruginosa 10,
      which both induced "suicidal" NETosis in an autophagy- and reactive oxygen
      species (ROS)-dependent, but TLR4-independent manner. Intriguingly, in whole
      blood cultures ex vivo, or in vitro in the presence of platelets, all LPS
      serotypes induced "vital" NET formation. This platelet-dependent release of NETs
      occurred rapidly without neutrophil cell death and was independent from ROS
      formation and autophagy but required platelet TLR4 and CD62P-dependent platelet
      neutrophil interactions. Taken together, our data reveal a complex interplay
      between neutrophils and LPS, which can induce both "suicidal" and "vital"
      NETosis, depending on the bacterial origin of LPS and the presence or absence of
      platelets. Our findings suggest that LPS sensing by neutrophils may be a critical
      determinant for restricting NET release to certain Gram-negative bacteria only,
      which in turn may be crucial for minimizing unnecessary NET-associated
      immunopathology.

PMID- 27867388
TI  - Transcriptomic Changes of Drought-Tolerant and Sensitive Banana Cultivars Exposed
      to Drought Stress.
AB  - In banana, drought responsive gene expression profiles of drought-tolerant and
      sensitive genotypes remain largely unexplored. In this research, the
      transcriptome of drought-tolerant banana cultivar (Saba, ABB genome) and
      sensitive cultivar (Grand Naine, AAA genome) was monitored using mRNA-Seq under
      control and drought stress condition. A total of 162.36 million reads from
      tolerant and 126.58 million reads from sensitive libraries were produced and
      mapped onto the Musa acuminata genome sequence and assembled into 23,096 and
      23,079 unigenes. Differential gene expression between two conditions (control and
      drought) showed that at least 2268 and 2963 statistically significant,
      functionally known, non-redundant differentially expressed genes (DEGs) from
      tolerant and sensitive libraries. Drought has up-regulated 991 and 1378 DEGs and
      down-regulated 1104 and 1585 DEGs respectively in tolerant and sensitive
      libraries. Among DEGs, 15.9% are coding for transcription factors (TFs)
      comprising 46 families and 9.5% of DEGs are constituted by protein kinases from
      82 families. Most enriched DEGs are mainly involved in protein modifications,
      lipid metabolism, alkaloid biosynthesis, carbohydrate degradation, glycan
      metabolism, and biosynthesis of amino acid, cofactor, nucleotide-sugar, hormone,
      terpenoids and other secondary metabolites. Several, specific genotype-dependent
      gene expression pattern was observed for drought stress in both cultivars. A
      subset of 9 DEGs was confirmed using quantitative reverse transcription-PCR.
      These results will provide necessary information for developing drought-resilient
      banana plants.

PMID- 27867389
TI  - Modeling the Morphometric Evolution of the Maize Shoot Apical Meristem.
AB  - The maize (Zea mays subsp. mays L.) shoot apical meristem (SAM) is a self
      replenishing pool of stem cells that produces all above-ground plant tissues.
      Improvements in image acquisition and processing techniques have allowed high
      throughput, quantitative genetic analyses of SAM morphology. As with other large
      scale phenotyping efforts, meaningful descriptions of genetic architecture depend
      on the collection of relevant measures. In this study, we tested two quantitative
      image processing methods to describe SAM morphology within the genus Zea,
      represented by 33 wild relatives of maize and 841 lines from a domesticated maize
      by wild teosinte progenitor (MxT) backcross population, along with previously
      reported data from several hundred diverse maize inbred lines. Approximating the
      MxT SAM as a paraboloid derived eight parabolic estimators of SAM morphology that
      identified highly overlapping quantitative trait loci (QTL) on eight chromosomes,
      which implicated previously identified SAM morphology candidate genes along with
      new QTL for SAM morphological variation. Using a Fourier-transform related method
      of comprehensive shape analysis, we detected cryptic SAM shape variation that
      identified QTL on six chromosomes. We found that Fourier transform shape
      descriptors and parabolic estimation measures are highly correlated and
      identified similar QTL. Analysis of shoot apex contours from 73 anciently
      diverged plant taxa further suggested that parabolic shape may be a universal
      feature of plant SAMs, regardless of evolutionary clade. Future high-throughput
      examinations of SAM morphology may benefit from the ease of acquisition and
      phenotypic fidelity of modeling the SAM as a paraboloid.

PMID- 27867390
TI  - The Mechanisms of Maize Resistance to Fusarium verticillioides by Comprehensive
      Analysis of RNA-seq Data.
AB  - Fusarium verticillioides is the most commonly reported fungal species responsible
      for ear rot of maize which substantially reduces grain yield. It also results in
      a substantial accumulation of mycotoxins that give rise to toxic response when
      ingested by animals and humans. For inefficient control by chemical and agronomic
      measures, it thus becomes more desirable to select more resistant varieties.
      However, the molecular mechanisms underlying the infection process remain poorly
      understood, which hampers the application of quantitative resistance in breeding
      programs. Here, we reveal the disease-resistance mechanism of the maize inbred
      line of BT-1 which displays high resistance to ear rot using RNA high throughput
      sequencing. By analyzing RNA-seq data from the BT-1 kernels before and after F.
      verticillioides inoculation, we found that transcript levels of genes associated
      with key pathways are dramatically changed compared with the control treatment.
      Differential gene expression in ear rot resistant and susceptible maize was
      confirmed by RNA microarray and qRT-PCR analyses. Further investigation suggests
      that the small heat shock protein family, some secondary metabolites, and the
      signaling pathways of abscisic acid, jasmonic acid, or salicylic acids (SA) may
      be involved in the pathogen-associated molecular pattern-triggered immunity
      against F. verticillioides. These data will not only provide new insights into
      the molecular resistant mechanisms against fungi invading, but may also result in
      the identification of key molecular factors associated with ear rot resistance in
      maize.

PMID- 27867391
TI  - Origin of the Autophagosomal Membrane in Plants.
AB  - During autophagy, cargo molecules destined for degradation are sequestrated into
      a double-membrane structure called autophagosome, which subsequently fuses with
      the vacuole. An isolation membrane structure (also called the phagophore)
      initiates from the platform termed PAS (phagophore assembly site or
      preautophagosomal structure), which then elongates and expands to become the
      completed autophagosome. The origin of the membrane for autophagosome formation
      has been extensively investigated but remains an enigma in the field of
      autophagy. In yeast and mammalian cells multiple membrane sources have been
      suggested to contribute to autophagosome formation at different steps, from
      initiation through expansion and maturation. Recent studies in plants have
      provided a significant advance in our understanding of the conserved role of
      autophagy and the underlying mechanism for autophagosome formation. Here, we will
      discuss and evaluate these new findings on autophagosome formation in plants,
      with a particular focus on the origin of plant autophagosomal membranes.

PMID- 27867393
TI  - Melatonin Application to Pisum sativum L. Seeds Positively Influences the
      Function of the Photosynthetic Apparatus in Growing Seedlings during Paraquat
      Induced Oxidative Stress.
AB  - Melatonin, due to its pleiotropic effects plays an important role improving
      tolerance to stresses. Plants increase endogenous melatonin synthesis when faced
      with harsh environments as well as exogenously applied melatonin limits stress
      injuries. Presented work demonstrated that single melatonin application into the
      seeds during pre-sowing priming improved oxidative stress tolerance of growing
      seedlings exposed to paraquat (PQ). PQ is a powerful herbicide which blocks the
      process of photosynthesis under light conditions due to free radicals excess
      production, when O2 is rapidly converted to [Formula: see text] and subsequently
      to other reactive oxygen species. The parameters of chlorophyll fluorescence
      [Fv/Fm, Fv/Fo, Rfd, PhiPSII, qP, and non-photochemical quenching (NPQ)] in all
      variants of pea leaves (derived from control non-treated seeds - C, and those
      hydroprimed with water - H, and hydroprimed with melatonin water solution 50 or
      200 MUM - H-MEL50 and H-MEL200, respectively) were analyzed as a tool for
      photosynthetic efficacy testing. Moreover stability of the photosynthetic
      pigments (chlorophylls a, b, and carotenoids) was also monitored under oxidative
      stress conditions. The results suggest that melatonin applied into the seed
      significantly enhances oxidative stress tolerance in growing seedlings. This
      beneficial effect was reflected in reduced accumulation of [Formula: see text] in
      leaf tissues, preservation of photosynthetic pigments, improved functioning of
      the photosynthetic apparatus and higher water content in the tissues during PQ
      mediated stress. Our findings provide evidence for the physiological role of this
      molecule and serve as a platform for its possible applications in agricultural or
      related areas of research.

PMID- 27867394
TI  - Association of Tissue Transglutaminase Antibody Titer with Duodenal Histological
      Changes in Children with Celiac Disease.
AB  - Celiac disease is usually diagnosed by demonstrating gluten enteropathy in small
      bowel biopsy. Celiac specific antibodies are used as an initial screening test.
      The goal of this study is to test the relationship of the anti-tTG titer and
      severity of histological changes in Jordanian children with celiac disease.
      Method. The medical records of 81 children who had elevated anti-tTG titer and
      had duodenal biopsies available were retrospectively reviewed. Result. Assessing
      the association of anti-tTG titer with duodenal histopathological changes, 94% of
      those with high anti-tTG titer (>=180 U/mL) had histological evidence of celiac
      disease. There was statistically significant positive association between high
      anti-tTG titer and Marsh grading as 82% of patients with Marsh III had high anti
      tTG titer (Chi2 18.5; P value 0.00; Odds Ratio 8.5). The fraction of patients
      with Marsh III who were correctly identified as positive by anti-tTG titer >= 180
      U/mL was high (sensitivity = 81.6). Moreover, the fraction of patients with anti
      tTG titer >= 180 U/mL who had Marsh III was also high (positive predictive value
      = 78.4). Conclusion. Anti-tTG titer >= 180 U/mL had significant positive
      association with Marsh III histopathological changes of celiac disease.

PMID- 27867392
TI  - The Physcomitrella patens Chloroplast Proteome Changes in Response to
      Protoplastation.
AB  - Plant protoplasts are widely used for genetic manipulation and functional studies
      in transient expression systems. However, little is known about the molecular
      pathways involved in a cell response to the combined stress factors resulted from
      protoplast generation. Plants often face more than one type of stress at a time,
      and how plants respond to combined stress factors is therefore of great interest.
      Here, we used protoplasts of the moss Physcomitrella patens as a model to study
      the effects of short-term stress on the chloroplast proteome. Using label-free
      comparative quantitative proteomic analysis (SWATH-MS), we quantified 479
      chloroplast proteins, 219 of which showed a more than 1.4-fold change in
      abundance in protoplasts. We additionally quantified 1451 chloroplast proteins
      using emPAI. We observed degradation of a significant portion of the chloroplast
      proteome following the first hour of stress imposed by the protoplast isolation
      process. Electron-transport chain (ETC) components underwent the heaviest
      degradation, resulting in the decline of photosynthetic activity. We also
      compared the proteome changes to those in the transcriptional level of nuclear
      encoded chloroplast genes. Globally, the levels of the quantified proteins and
      their corresponding mRNAs showed limited correlation. Genes involved in the
      biosynthesis of chlorophyll and components of the outer chloroplast membrane
      showed decreases in both transcript and protein abundance. However, proteins like
      dehydroascorbate reductase 1 and 2-cys peroxiredoxin B responsible for ROS
      detoxification increased in abundance. Further, genes such as thylakoid ascorbate
      peroxidase were induced at the transcriptional level but down-regulated at the
      proteomic level. Together, our results demonstrate that the initial chloroplast
      reaction to stress is due changes at the proteomic level.

PMID- 27867395
TI  - Radioactive Iodine Administration Is Associated with Persistent Related Symptoms
      in Patients with Differentiated Thyroid Cancer.
AB  - Context. Radioiodine (RAI) administration has adverse effects in patients treated
      for thyroid cancer (DTC), but there is scarce information regarding their
      intensity and duration. Objective. To evaluate frequency and intensity of early
      and late RAI-related symptoms in patients with DTC. Design. Observational
      prospective study. Patients. DTC patients who underwent thyroidectomy, with or
      without RAI. Measurements. Patients answered 2 surveys: (1) from 0 to 6 months
      and (2) between 6 and 18 months after initial treatment. Results. 110 patients
      answered the first survey and 61 both. Nearly 80 percent received RAI. Among
      early symptoms, periorbital edema, excessive tearing, salivary gland
      disturbances, dry mouth, taste disorders, and nausea were more frequent and
      intense among RAI patients. Regarding late symptoms, periorbital edema, salivary
      gland pain and swelling, and dry mouth were more frequent and intense in RAI
      patients. Frequency and intensity of adverse effects were not different between
      low and high RAI doses (50 versus >=100 mCi). Conclusion. RAI-related symptoms
      are frequent and usually persist after 6 months of administration, even when low
      doses are given. This finding must be considered when deciding RAI
      administration, especially in low risk patients, among whom RAI benefit is
      controversial.

PMID- 27867397
TI  - Knowledge and Awareness of Cervical Cancer among HIV-Infected Women in Ethiopia.
AB  - Introduction. Cervical cancer is one of the leading causes of cancer death among
      Ethiopian women. Low awareness of cervical cancer, in combination with low health
      care seeking behavior, is a key challenge for cervical cancer prevention. This
      study assessed the knowledge of cervical cancer among HIV-infected women in
      Ethiopia. Methods. A facility-based cross-sectional survey was conducted from
      August to September 2012 among HIV-infected women between 21 and 49 years of age.
      Basic descriptive statistics were performed using SPSS. Results. A total of 432
      HIV-infected women participated in this study. About 71% of participants had ever
      heard of cervical cancer. Among women who had ever heard of cervical cancer, 49%
      did not know the cause while 74% were able to identify at least one risk factor
      for cervical cancer. Only 33% of women were able to correctly address when women
      should seek care and 33% identified at least one treatment option for cervical
      cancer. Conclusion. This study revealed that knowledge about cervical cancer was
      generally low, in particular for health care seeking behavior and treatment of
      cervical cancer. Health awareness programs should be strengthened at both
      community and health facility levels with emphasis highlighting the causes, risk
      factors, care seeking behaviors, and treatment options for cervical cancer.

PMID- 27867396
TI  - Challenges in the Diagnosis and Management of Growth Hormone Deficiency in India.
AB  - In clinical practice, every year approximately 150,000 children are referred with
      short stature (SS) based on a cut-off of fifth percentile. The most important
      endocrine and treatable cause of SS is growth hormone deficiency (GHD). The lack
      of reliable data on the prevalence of GHD in India limits estimation of the
      magnitude of this problem. The diagnosis and treatment of GHD are hurdled with
      various challenges, restricting the availability of growth hormone (GH) therapy
      to only a very limited segment of the children in India. This review will firstly
      summarize the gaps and challenges in diagnosis and treatment of GHD based on
      literature analysis. Subsequently, it presents suggestions from the members at
      advisory board meetings to overcome these challenges. The advisory board
      suggested that early initiation of the therapy could better the chances of
      achieving final adult height within the normal range for the population.
      Education and awareness about growth disorders among parents, regular training
      for physicians, and more emphasis on using the Indian growth charts for growth
      monitoring would help improve the diagnosis and treatment of children with GHD.
      Availability of an easy-to-use therapy delivery system could also be beneficial
      in improving adherence and achieving satisfactory outcomes.

PMID- 27867399
TI  - Biodemographic Analysis of Factors Related to Perinatal Mortality in Portugal
      (1988-2011).
AB  - Background. The purpose of this paper is to determine the relative mortality
      risks at delivery and during the first week of life with regard to maternal and
      foetal characteristics. Methods. Yearly individual digital records on live births
      and early neonatal mortality were used to infer the possible factors involved in
      perinatal deaths. Results. The results show that the number of births per year
      declined with time throughout the period studied. At the same time, rates
      decreased in 66.4% for stillbirths and in 70.2% for early neonatal mortality.
      Logistic regressions modelled the interaction of the two mortality indicators and
      covariables such as birth weight and the duration of gestation. Conclusions. This
      research provides a first biodemographic approach to the knowledge of factors
      influencing perinatal mortality in Portugal based on a set of foetal and maternal
      variables. Although the magnitude of the different perinatal mortality rates may
      be affected by the criteria used for selecting cases (multiple-singletons;
      minimum birth weight or minimum duration of gestation), one of the conclusions of
      the present analysis is that the relationship among the maternal and foetal
      variables that determine the relative risk remains unaltered. Certain resemblance
      with the factors determining negative birth outcomes in Spain is appreciated.

PMID- 27867400
TI  - Climate Change Impact: The Experience of the Coastal Areas of Bangladesh Affected
      by Cyclones Sidr and Aila.
AB  - Bangladesh is considered one of the countries most at risk to the effects of
      climate change and its coastal area is most vulnerable. This study tries to
      explore the experiences of cyclones Sidr and Aila affected people living in the
      coastal areas of Bangladesh. This study was conducted in the cyclone Sidr
      affected Amtali Upazila of Barguna District and in the cyclone Aila affected
      Koyra Upazila of Khulna District. Primary data collection was done using Focus
      Group Interview and then a thematic analysis approach was used for analysis.
      Three core themes emerged from the analysis and they are, firstly, impacts of
      climate change on the socioeconomic condition of the people, secondly, the impact
      on the health status of the population, and finally the impact on vulnerable
      people. Findings show that the effects of climate change have serious
      consequences on the livelihood patterns of the affected population and on their
      overall health status. As a result, the unfavorable health condition of these
      affected people makes them more vulnerable to various emerging diseases.

PMID- 27867401
TI  - KRAS mutant tumor subpopulations can subvert durable responses to personalized
      cancer treatments.
AB  - KRAS mutations in colorectal and lung cancers predict failure to respond to
      therapies that target the EGFR. Significant percentages of patients with KRAS
      wild-type tumors also fail to respond to these therapies. Relapse occurs in
      patients with KRAS wild-type and mutant tumors, with moderately longer
      progression-free survival in patients with KRAS wild-type tumors. Colon and lung
      tumors frequently carry KRAS mutant tumor subpopulations not detected by DNA
      sequencing. This suggests detected and undetected KRAS mutant subpopulations in
      colon and lung tumors are undermining the efficacy of anti-EGFR therapies.
      Therefore, consideration should be given to combining therapies that target KRAS
      mutant cells with those that downregulate EGFR signaling. As tumors are
      frequently polyclonal in origin and comprised of distinct clonal populations
      carrying complementing genetic and/or epigenetic lesions, preclinical models that
      assess the efficacy of combination therapies in the context of heterogeneous
      tumor cell populations will be essential for progress in this area.

PMID- 27867398
TI  - Mesenchymal Stem Cells as a Prospective Therapy for the Diabetic Foot.
AB  - The diabetic foot is a serious complication of diabetes. Mesenchymal stem cells
      are an abundant source of stem cells which occupy a special position in cell
      therapies, and recent studies have suggested that mesenchymal stem cells can play
      essential roles in treatments for the diabetic foot. Here, we discuss the
      advances that have been made in mesenchymal stem cell treatments for this
      condition. The roles and functional mechanisms of mesenchymal stem cells in the
      diabetic foot are also summarized, and insights into current and future studies
      are presented.

PMID- 27867402
TI  - Evaluation of Hypoglycemic and Genotoxic Effect of Polyphenolic Bark Extract from
      Quercus sideroxyla.
AB  - Quercus sideroxyla is a wood species whose bark has phenolic compound and should
      be considered to be bioactive; the hypoglycemic and genotoxic properties of Q.
      sideroxyla bark were evaluated in this study. Total phenolic compound was
      determined in crude extract (CE) and organic extract (OE). The OE has the highest
      amount of phenols (724.1 +/- 12.0 GAE/g). Besides, both CE and OE demonstrated
      effect over the inhibition of alpha-amylase in vitro. Hypoglycemic activity was
      assessed by glucose tolerance curve and the area under curve (UAC); OE showed the
      highest hypoglycemic activity. In addition, diabetes was induced by
      streptozotocin (65 mg/kg) and the extracts (50 mg/kg) were administered for 10
      days; OE showed hypoglycemic effect compared with diabetic control and decreased
      hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE;
      results of acute toxicity did not show any mortality. Besides, the comet assay
      showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when
      evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the
      formation of type 1 comets.

PMID- 27867404
TI  - Editorial.

PMID- 27867403
TI  - In Vitro TNF-alpha Inhibitory Activity of Brazilian Plants and Anti-Inflammatory
      Effect of Stryphnodendron adstringens in an Acute Arthritis Model.
AB  - Stryphnodendron species, popularly named "barbatimao," are traditionally used in
      Brazil as anti-inflammatory agents. This study aimed to investigate the effect of
      barbatimao and 11 other species on the production of tumor necrosis factor-alpha
      (TNF-alpha) in lipopolysaccharide- (LPS-) stimulated THP-1 cells, as well as
      their anti-arthritis activity. The extracts of Stryphnodendron adstringens,
      Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens
      promoted a concentration-dependent inhibition of TNF-alpha. Mice injected with
      LPS in the knee joint were treated per os with fractions from the selected
      extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S.
      adstringens promoted a dose-dependent reduction of leukocyte migration and
      neutrophil accumulation into the joint, but none of them reduced CXCL1
      concentration in the periarticular tissue. In contrast, treatment with C.
      lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory
      parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC)
      coupled to electrospray ionization mass spectrometry (ESI-MS) led to the
      identification of gallic acid along with 11 prodelphinidins, characterized as
      monomers and dimers of the B-type. Our findings contribute to some extent to
      corroborating the traditional use of S. adstringens as an anti-inflammatory
      agent. This activity is probably related to a decrease of leukocyte migration
      into the inflammatory site. Polyphenols like gallic acid and prodelphinidins,
      identified in the active fraction, may contribute to the observed activity.

PMID- 27867406
TI  - Helping expectant mothers understand inadequate ultrasound images.
AB  - BACKGROUND: Obstetric ultrasound scans may fail to provide all the information
      that is needed because of poor visualisation. Two main causes of poor
      visualisation are addressed. These are poor foetal position and poor quality
      imaging due to beam distortion by overlying fatty tissue. METHOD: To improve
      communication with patients attending obstetric scans, a poster and leaflet were
      designed to explain these causes of inadequate scans. A questionnaire was used to
      assess the value of the poster. RESULTS: 57/66 (86%) questionnaires were
      completed. 52 (91%) found the information on the poster was helpful and well
      explained. For 8 (14%) the information changed their thoughts about the scan.
      CONCLUSION: Clear communication aids the expectant mothers understanding of why
      scans may be suboptimal. The way this is recorded in the scan results is
      discussed.

PMID- 27867405
TI  - Development and assessment of inter- and intra-rater reliability of a novel
      ultrasound tool for scoring tendon and sheath disease - A pilot study.
AB  - BACKGROUND: Tendon and synovial sheath disease is common. A method of monitoring
      the status of tendons and sheaths is important for both diagnosis of pathology
      and evaluation of the efficacy of treatments. For this study, an ultrasound
      scoring tool was developed and its reliability tested between raters. The tool is
      novel in that it scores tendons and sheaths separately, an important
      consideration since disorders of these structures are not necessarily concurrent.
      METHODS: Thirty diseased tendons and sheaths were included in this pilot cross
      sectional study. Tendon and sheath measurements were taken and the semi
      quantitative five-grade score was applied to assess tendon greyscale, tendon
      Doppler activity and sheath Doppler activity. Inter-rater and intra-rater
      agreement exercises were undertaken to test the reliability of the scoring tool.
      RESULTS: The Intra-class Correlation Coefficient values for both the inter-rater
      and intra-rater reliability tests showed excellent agreement for the tendon and
      sheath measurements. Unweighted kappa estimations for inter-rater scores showed
      excellent agreement for tendon Doppler; good agreement was shown for scoring
      sheath Doppler, while poor agreement was shown for tendon grey-scale scoring. The
      intra-rater reliability scores demonstrated similar results. CONCLUSION: Overall,
      the study strongly supports the use of this scoring tool for the diagnosis and
      follow-up of tendon and sheath disorders. The results may be used as a starting
      point from which to base further work in this important area. Future studies
      should address the limitations found in this research with a strong focus on
      improving tendon grey-scale measurement accuracy and agreement.

PMID- 27867407
TI  - Twinkle artefact in the ultrasound diagnosis of superficial epidermoid cysts.
AB  - AIM: The aim of the study was to evaluate whether the twinkle artefact is a
      valuable feature in the sonographic diagnosis of superficial epidermoid cysts.
      MATERIALS AND METHODS: A retrospective search was undertaken of our institution's
      Radiology Information System and pathology database to identify cases of
      superficial masses showing the twinkle artefact that proceeded to surgical
      excision. RESULTS: Eighteen superficial masses demonstrating the twinkle artefact
      were identified that were submitted for pathological analysis. Of these, 17 were
      confirmed to represent epidermoid cysts and only 1 case had an alternative
      diagnosis (proliferating trichilemmal cyst). CONCLUSION: The presence of the
      twinkle artefact appears to be a specific and valuable ancillary sonographic
      feature for the diagnosis of superficial epidermoid cysts.

PMID- 27867408
TI  - Reliability of a measurement method for the cross-sectional area of the longus
      colli using real-time ultrasound imaging.
AB  - OBJECTIVE: Real-time ultrasound imaging is an established objective outcome
      measurement with proven reliability. However, it is still largely biased by user
      ability. Published research in the area of real-time ultrasound imaging
      reliability in the cervical region and in particular the deep cervical flexors is
      quite sparse. The purpose of this investigation was to examine if a novice
      ultrasound user could agree favourably with an experienced ultrasound sonographer
      in measuring the cross-sectional area of the longus colli. METHODS: Ultrasound
      images were captured from 22 healthy subjects on two different occasions, one
      week apart, by a novice ultrasound user. They were acquired using a GE Healthcare
      LOGIQe ultrasound machine, at a depth of 3-4 cm with the transducer frequency set
      to 8 MHz, in line with previous research guidelines. Cross-sectional area was
      then measured on-screen by both a novice and experienced ultrasound user to
      determine inter-rater reliability. Intra-rater reliability was also analysed
      using cross-sectional area figures from days one and two. RESULTS: Intra-rater
      reliability for real-time ultrasound imaging for the cross-sectional area of the
      longus colli was "excellent" (intra-class correlation 0.90, 95% CI 0.82-0.95).
      Inter-rater reliability was "moderate" but in keeping with previous published
      research (intra-class correlation 0.61, 95% CI 0.37-0.77). CONCLUSION:
      Difficulties in identifying the borders of the longus colli muscle due to its
      deep anatomical location and surrounding structures make it difficult for
      assessors to agree favourably on cross-sectional area measurements, leading to
      "moderate" levels of inter-rater reliability and poor agreement. Intra-rater
      reliability is excellent, and in this instance indicates that a novice user can
      be just as reliable as a more experienced ultrasound user.

PMID- 27867409
TI  - The postpartum ultrasound scan.
AB  - Ultrasound assessment of the postpartum uterus has a significant role to play in
      the evaluation of a large proportion of symptomatic puerperal women. Often the
      imaging modality of choice for excluding retained placental tissue, correct
      application of postpartum ultrasound could enable more accurate identification of
      women requiring surgical intervention, with consequent reduction in patient
      morbidity and clinical workload. This article aims to review the current
      understanding and application of ultrasound in the puerperium and evaluate the
      current evidence investigating the physiological and pathological findings of the
      postpartum uterus and its contents.

PMID- 27867410
TI  - Closed gastroschisis, vanishing midgut and extreme short bowel syndrome: Case
      report and review of the literature.
AB  - Gastroschisis alone has excellent survival rates. Occasionally reported is closed
      gastroschisis, leading to vanishing small bowel and extreme short bowel syndrome.
      It is believed that the abdominal wall defect can contract or close in utero,
      which leads to strangulation of the eviscerated bowel and the rare "vanishing gut
      syndrome." This has a very poor prognosis with mortality as high as 70%. An 18
      year-old primigravid patient's 13 week scan diagnosed a large gastroschisis
      affecting the fetus. After counselling, she decided to continue with the
      pregnancy. Between 20 and 22 weeks, the gastroschisis disappeared, and the bowel
      within the abdomen became markedly dilated. Spontaneous labour occurred at 33 + 3
      weeks gestation. There was no abdominal wall defect seen at delivery. Imaging and
      an exploratory laparotomy demonstrated absence of most of the midgut. Because
      available options for treatment would be very aggressive and risky, palliative
      care was thought to be the most feasible and practical option. He died at home on
      day 29 after birth. Extreme short gut syndrome (less than 25 cm of remaining
      small bowel) is rare. There are 13 reported cases in the literature from year
      2000 to 2013. Treatment is aggressive and involves a bowel lengthening procedure
      or small bowel transplant. All require total parenteral nutrition and liver
      failure, and liver transplant is a common complication. Of these cases, 12 were
      born alive and 7 had aggressive treatment. Only two cases were confirmed to still
      be alive in infancy. If gastroschisis is seen to be reducing and "disappearing"
      antenatally, parents should be made aware of this rare complication so that they
      might be prepared if a poor outcome is anticipated.

PMID- 27867411
TI  - Ultrasound as a screening tool in the follow-up of asymptomatic congenital cystic
      adenomatoid malformation.
AB  - Congenital cystic adenomatoid malformation accounts for the vast majority of
      congenital cystic lung pathologies. The clinical spectrum of congenital cystic
      adenomatoid malformation is wide and ranges from silent incidental lesions to
      severe congenital respiratory distress or stillbirths. Management of clinically
      silent lesions is still a matter of debate, with conservative follow-up being a
      popular approach during the last decade. However, an optimal methodology of
      follow-up is yet to be determined. In this study, ultrasound is proposed as a
      follow-up tool for clinically silent lesions based on the findings in a case with
      known congenital cystic adenomatoid malformation from the antenatal period, which
      has been followed up for four years.

PMID- 27867413
TI  - A Parent-Based Intervention to Prevent HIV Among Adolescent Children of Mothers
      Living with HIV: The Ms. Now! Program.
AB  - One group often overlooked by HIV prevention efforts is adolescent children of
      mothers living with HIV (MLH). Despite their potential vulnerability, very few
      evidence-based prevention programs exist for this population in the United States
      (U.S.) and elsewhere. The current study introduces a parent-based program adapted
      for families affected by HIV for the purpose of preventing adolescent HIV
      infection. Following a structured process of adaptation, 12 African American MLH
      adolescent dyads were recruited from HIV clinics and non-governmental
      organizations in a southeastern U.S. city to participate in a feasibility pilot
      evaluation of the adapted program (Moms Stopping It Now! [Ms. Now]). The
      intervention consisted of group and individual sessions implemented in a
      university setting and at participants' homes, respectively. We determined
      feasibility through assessing participant acceptability and signs of intervention
      efficacy. Quantitative and qualitative process data revealed high levels of
      acceptability, as participants were largely satisfied and engaged with Ms. Now,
      and were willing to attend most sessions. In addition, positive intervention
      effects approaching medium to large effect sizes were observed for some
      protective parenting outcomes, including increases in parent-child relationship
      quality, parental monitoring, maternal HIV disclosure self-efficacy, and
      communication about maternal HIV infection. Other outcomes, namely communication
      about sex topics, did not show positive shifts due to ceiling effects and may be
      indicative of the pre-existing strengths these MLH possess. Ms. Now's approach
      and further refinement is discussed in the context of strengthening families
      affected by HIV. Moreover, we recommend that policy aimed at program development
      consider jointly targeting these populations (MLH and adolescents) due to the
      unique benefits of family intervention.

PMID- 27867414
TI  - The Role of Family Variables in the Length of Stay of Psychiatric In-patients.
AB  - BACKGROUND: In Japan, the number of beds and average length of stay in a
      psychiatric ward are greater than in other developed countries. OBJECTIVE: The
      present study aimed to investigate the association between family variables and
      the length of stay of patients with mental and behavioural disorders in a private
      psychiatric hospital in Japan. METHODS: The medical records of patients
      discharged during a one-year period (n=56: men 50.0% excepting 27 patients
      discharged due to death were re-examined regarding age, laundry type (self
      washing of clothes, family washing or supplier washing), number of family visits
      per one month while hospitalised, and family structure prior to hospitalisation.
      A length of stay greater than six months was considered the cut-off point for a
      long hospital stay. Bivariate logistic regression analyses were conducted to
      identify factors independently associated with the length of stay, adjusted for
      sex, age, and mental and/or behavioural disorders according to the criteria of
      the International Statistical Classification of Diseases and Related Health
      Problems. RESULTS: The bivariate-adjusted odds ratio (95% confidence intervals)
      for in-patients hospitalised for more than six months was 0.08 (0.01, 0.48) for
      those who used family washing (p = 0.006) compared with those who used supplier
      washing. The number of visits per month and family structures before
      hospitalisation were not significantly associated. CONCLUSION: These results
      suggest that within a private psychiatric hospital in Japan, family washing is
      associated with shortened stays and frequency of family visits, while family
      structure is not associated with these factors.

PMID- 27867415
TI  - Prior Acute Mental Exertion in Exercise and Sport.
AB  - INTRODUCTION: Mental exertion is a psychophysiological state caused by sustained
      and prolonged cognitive activity. The understanding of the possible effects of
      acute mental exertion on physical performance, and their physiological and
      psychological responses are of great importance for the performance of different
      occupations, such as military, construction workers, athletes (professional or
      recreational) or simply practicing regular exercise, since these occupations
      often combine physical and mental tasks while performing their activities.
      However, the effects of implementation of a cognitive task on responses to
      aerobic exercise and sports are poorly understood. Our narrative review aims to
      provide information on the current research related to the effects of prior acute
      mental fatigue on physical performance and their physiological and psychological
      responses associated with exercise and sports. METHODS: The literature search was
      conducted using the databases PubMed, ISI Web of Knowledge and PsycInfo using the
      following terms and their combinations: "mental exertion", "mental fatigue",
      "mental fatigue and performance", "mental exertion and sports" "mental exertion
      and exercise". RESULTS: We concluded that prior acute mental exertion affects
      effectively the physiological and psychophysiological responses during the
      cognitive task, and performance in exercise. CONCLUSION: Additional studies
      involving prior acute mental exertion, exercise/sports and physical performance
      still need to be carried out in order to analyze the physiological,
      psychophysiological and neurophysiological responses subsequently to acute mental
      exertion in order to identify cardiovascular factors, psychological,
      neuropsychological associates.

PMID- 27867416
TI  - Acute Affective Responses and Frontal Electroencephalographic Asymmetry to
      Prescribed and Self-selected Exercise.
AB  - OBJECTIVE: Our goal was to compare affective responses and frontal
      electroencephalographic alpha asymmetry induced by prescribed exercise (PE) and
      self-selected exercise (SS). METHOD: Twenty active participants underwent a
      submaximal exercise test to estimate maximal oxygen consumption (VO2max).
      Participants enrolled a cross-over randomized study where each participant
      completed three conditions: PE (50%PVO2max), SS and Control. The
      electroencephalography was performed before and after exercise. The feeling
      scale, felt arousal scale and heart rate were recorded before, during and after
      each condition. The ratings of perceived exertion were recorded during and after
      each condition. RESULTS: The heart rate and ratings of perceived exertion showed
      higher values in the PE and SS conditions compared to controls, with no
      differences between the PE and SS conditions. For the feeling scale, the SS
      presented higher values compared to the PE and Control conditions. The felt
      arousal scale presented higher values in the PE and SS conditions compared to
      control. There was no interaction between condition and moment, or main effect
      for condition and moment for frontal alpha asymmetry (InF4-InF3). CONCLUSION: The
      SS provided better affective responses compared to PE, thus can consider self
      selected intensity as an appropriate option. In general, no frontal alpha
      asymmetry was seen due to an exercise intervention.

PMID- 27867418
TI  - CRF-Based Model for Instrument Detection and Pose Estimation in Retinal
      Microsurgery.
AB  - Detection of instrument tip in retinal microsurgery videos is extremely
      challenging due to rapid motion, illumination changes, the cluttered background,
      and the deformable shape of the instrument. For the same reason, frequent
      failures in tracking add the overhead of reinitialization of the tracking. In
      this work, a new method is proposed to localize not only the instrument center
      point but also its tips and orientation without the need of manual
      reinitialization. Our approach models the instrument as a Conditional Random
      Field (CRF) where each part of the instrument is detected separately. The
      relations between these parts are modeled to capture the translation, rotation,
      and the scale changes of the instrument. The tracking is done via separate
      detection of instrument parts and evaluation of confidence via the modeled
      dependence functions. In case of low confidence feedback an automatic recovery
      process is performed. The algorithm is evaluated on in vivo ophthalmic surgery
      datasets and its performance is comparable to the state-of-the-art methods with
      the advantage that no manual reinitialization is needed.

PMID- 27867417
TI  - From Asperger's Autistischen Psychopathen to DSM-5 Autism Spectrum Disorder and
      Beyond: A Subthreshold Autism Spectrum Model.
AB  - Growing interest has recently been devoted to partial forms of autism, lying at
      the diagnostic boundaries of those conditions previously diagnosed as Asperger's
      Disorder. This latter includes an important retrieval of the European classical
      psychopathological concepts of adult autism to which Hans Asperger referred in
      his work. Based on the review of Asperger's Autistische Psychopathie, from first
      descriptions through the DSM-IV Asperger's Disorder and up to the recent DSM-5
      Autism Spectrum Disorder, the paper aims to propose a Subthreshold Autism
      Spectrum Model that encompasses not only threshold-level manifestations but also
      mild/atypical symptoms, gender-specific features, behavioral manifestations and
      personality traits associated with Autism Spectrum Disorder. This model includes,
      but is not limited to, the so-called broad autism phenotype spanning across the
      general population that does not fully meet Autism Spectrum Disorder criteria.
      From this perspective, we propose a subthreshold autism as a unique
      psychological/behavioral model for research that could help to understand the
      neurodevelopmental trajectories leading from autistic traits to a broad range of
      mental disorders.

PMID- 27867419
TI  - Combined Application of Ultrasound and CT Increased Diagnostic Value in Female
      Patients with Pelvic Masses.
AB  - Purpose. The current study aimed to evaluate whether combined application of
      ultrasound and CT had increased Diagnostic Value in Female Patients with Pelvic
      Masses over either method alone. Patients and Methods. 240 female patients with
      pelvic masses were detected preoperatively with ultrasound and CT prior to
      surgery. The sensitivity, specificity, and accuracy of ultrasound, CT, and
      combined ultrasound/CT application were evaluated, respectively. Results. The
      sensitivity, specificity, and accuracy of ultrasound were 52.8%, 86.7%, and
      68.75%, respectively. The sensitivity, specificity, and accuracy of CT were
      80.3%, 90.3%, and 85%, respectively. The sensitivity, specificity, and accuracy
      of combined application of ultrasound and CT were 89%, 94.7%, and 91.7%. The
      sensitivity, specificity, and accuracy of combined application of ultrasound and
      CT were higher than those of either ultrasound or CT. Conclusions. The combined
      application of ultrasound and CT had higher Diagnostic Value in Female Patients
      with Pelvic Masses than either method alone.

PMID- 27867420
TI  - A Lattice Model of the Development of Reading Comprehension.
AB  - In this article, I present a developmental model of how children learn to
      comprehend what they read, which builds on current models of reading
      comprehension and integrates findings from instructional research and evidence
      based models of development in early and middle childhood. The lattice model
      holds that children's developing reading comprehension is a function of the
      interacting, reciprocal, and bootstrapping effects of developing text-specific,
      linguistic, and social-cognitive processes, which interact with instruction as
      child-characteristic-by-instruction (CXI) interaction effects. The processes
      develop over time and in the context of classroom, home, peer, community, and
      other influences to affect children's development of proficient reading
      comprehension. I first describe models of reading comprehension. I then review
      the basic processes in the model, the role of instruction, and CXI interactions
      in the context of the lattice model. I then discuss implications for instruction
      and research.

PMID- 27867421
TI  - Dedicated biomass crops can enhance biodiversity in the arable landscape.
AB  - Suggestions that novel, non-food, dedicated biomass crops used to produce
      bioenergy may provide opportunities to diversify and reinstate biodiversity in
      intensively managed farmland have not yet been fully tested at the landscape
      scale. Using two of the largest, currently available landscape-scale biodiversity
      data sets from arable and biomass bioenergy crops, we take a taxonomic and
      functional trait approach to quantify and contrast the consequences for
      biodiversity indicators of adopting dedicated biomass crops on land previously
      cultivated under annual, rotational arable cropping. The abundance and community
      compositions of biodiversity indicators in fields of break and cereal crops
      changed when planted with the dedicated biomass crops, miscanthus and short
      rotation coppiced (SRC) willow. Weed biomass was consistently greater in the two
      dedicated biomass crops than in cereals, and invertebrate abundance was similarly
      consistently higher than in break crops. Using canonical variates analysis, we
      identified distinct plant and invertebrate taxa and trait-based communities in
      miscanthus and SRC willows, whereas break and cereal crops tended to form a
      single, composite community. Seedbanks were shown to reflect the longer term
      effects of crop management. Our study suggests that miscanthus and SRC willows,
      and the management associated with perennial cropping, would support significant
      amounts of biodiversity when compared with annual arable crops. We recommend the
      strategic planting of these perennial, dedicated biomass crops in arable farmland
      to increase landscape heterogeneity and enhance ecosystem function, and
      simultaneously work towards striking a balance between energy and food security.

PMID- 27867422
TI  - ClassyFire: automated chemical classification with a comprehensive, computable
      taxonomy.
AB  - BACKGROUND: Scientists have long been driven by the desire to describe, organize,
      classify, and compare objects using taxonomies and/or ontologies. In contrast to
      biology, geology, and many other scientific disciplines, the world of chemistry
      still lacks a standardized chemical ontology or taxonomy. Several attempts at
      chemical classification have been made; but they have mostly been limited to
      either manual, or semi-automated proof-of-principle applications. This is
      regrettable as comprehensive chemical classification and description tools could
      not only improve our understanding of chemistry but also improve the linkage
      between chemistry and many other fields. For instance, the chemical
      classification of a compound could help predict its metabolic fate in humans, its
      druggability or potential hazards associated with it, among others. However, the
      sheer number (tens of millions of compounds) and complexity of chemical
      structures is such that any manual classification effort would prove to be near
      impossible. RESULTS: We have developed a comprehensive, flexible, and computable,
      purely structure-based chemical taxonomy (ChemOnt), along with a computer program
      (ClassyFire) that uses only chemical structures and structural features to
      automatically assign all known chemical compounds to a taxonomy consisting of
      >4800 different categories. This new chemical taxonomy consists of up to 11
      different levels (Kingdom, SuperClass, Class, SubClass, etc.) with each of the
      categories defined by unambiguous, computable structural rules. Furthermore each
      category is named using a consensus-based nomenclature and described (in English)
      based on the characteristic common structural properties of the compounds it
      contains. The ClassyFire webserver is freely accessible at
      http://classyfire.wishartlab.com/. Moreover, a Ruby API version is available at
      https://bitbucket.org/wishartlab/classyfire_api, which provides programmatic
      access to the ClassyFire server and database. ClassyFire has been used to
      annotate over 77 million compounds and has already been integrated into other
      software packages to automatically generate textual descriptions for, and/or
      infer biological properties of over 100,000 compounds. Additional examples and
      applications are provided in this paper. CONCLUSION: ClassyFire, in combination
      with ChemOnt (ClassyFire's comprehensive chemical taxonomy), now allows chemists
      and cheminformaticians to perform large-scale, rapid and automated chemical
      classification. Moreover, a freely accessible API allows easy access to more than
      77 million "ClassyFire" classified compounds. The results can be used to help
      annotate well studied, as well as lesser-known compounds. In addition, these
      chemical classifications can be used as input for data integration, and many
      other cheminformatics-related tasks.

PMID- 27867423
TI  - Marginalized zero-altered models for longitudinal count data.
AB  - Count data often exhibit more zeros than predicted by common count distributions
      like the Poisson or negative binomial. In recent years, there has been
      considerable interest in methods for analyzing zero-inflated count data in
      longitudinal or other correlated data settings. A common approach has been to
      extend zero-inflated Poisson models to include random effects that account for
      correlation among observations. However, these models have been shown to have a
      few drawbacks, including interpretability of regression coefficients and
      numerical instability of fitting algorithms even when the data arise from the
      assumed model. To address these issues, we propose a model that parameterizes the
      marginal associations between the count outcome and the covariates as easily
      interpretable log relative rates, while including random effects to account for
      correlation among observations. One of the main advantages of this marginal model
      is that it allows a basis upon which we can directly compare the performance of
      standard methods that ignore zero inflation with that of a method that explicitly
      takes zero inflation into account. We present simulations of these various model
      formulations in terms of bias and variance estimation. Finally, we apply the
      proposed approach to analyze toxicological data of the effect of emissions on
      cardiac arrhythmias.

PMID- 27867424
TI  - Aldehyde and Ketone Synthesis by P450-Catalyzed Oxidative Deamination of Alkyl
      Azides.
AB  - Heme-containing proteins have recently attracted increasing attention for their
      ability to promote synthetically valuable transformations not found in nature.
      Following the recent discovery that engineered variants of myoglobin can catalyze
      the direct conversion of organic azides to aldehydes, we investigated the azide
      oxidative deamination reactivity of a variety of hemoproteins featuring different
      heme coordination environments. Our studies show that although several heme
      containing enzymes possess basal activity in this reaction, an engineered variant
      of the bacterial cytochrome P450 CYP102A1 constitutes a particularly efficient
      biocatalyst for promoting this transformation, exhibiting a broad substrate scope
      along with high catalytic activity (up to 11,300 TON), excellent
      chemoselectivity, and enhanced reactivity toward secondary alkyl azides to yield
      ketones. Mechanistic studies and Michaelis-Menten analyses provided insights into
      the mechanism of the reaction and the impact of active site mutations on the
      catalytic properties of the P450. Altogether, these studies demonstrate that
      engineered P450 variants represent promising biocatalysts for the synthesis of
      aryl aldehydes and ketones via the oxidative deamination of alkyl azides under
      mild reaction conditions.

PMID- 27867426
TI  - Fragranced consumer products: exposures and effects from emissions.
AB  - Fragranced consumer products, such as cleaning supplies, air fresheners, and
      personal care products, are a primary source of indoor air pollutants and
      personal exposure. Previous research indicates that fragranced products can
      trigger adverse health effects, with implications for workplaces and public
      places. This is the first study to examine the multiple dimensions of exposures
      related to fragranced products and effects in the US population. The study
      investigated the prevalence and types of fragranced product exposures, associated
      health effects, awareness of product emissions, and preferences for fragrance
      free policies and environments. Data were collected using an online survey with a
      nationally representative population (n = 1136) of adults in the USA. Overall,
      34.7 % of the population reported health problems, such as migraine headaches and
      respiratory difficulties, when exposed to fragranced products. Further, 15.1 %
      have lost workdays or a job due to fragranced product exposure in the workplace.
      Also, 20.2 % would enter a business but then leave as quickly as possible if they
      smell air fresheners or some fragranced product. Over 50 % of the population
      would prefer that workplaces, health care facilities and professionals, hotels,
      and airplanes were fragrance-free. While prior research found that common
      fragranced products, even those called green and organic, emitted hazardous air
      pollutants, more than two thirds of the population were not aware of this, and
      over 60 % would not continue to use a fragranced product if they knew it emitted
      such pollutants. Results from this study provide strong evidence that fragranced
      products can trigger adverse health effects in the general population. The study
      also indicates that reducing exposure to fragranced products, such as through
      fragrance-free policies, can provide cost-effective and relatively simple ways to
      reduce risks and improve air quality and health.

PMID- 27867427
TI  - Practicalities of mapping PM10 and PM2.5 concentrations on city-wide scales using
      a portable particulate monitor.
AB  - Fine particulate matter is considered to be the most significant ambient air
      pollutant in terms of potential health impacts. Therefore, it is important that
      regulators are able to accurately assess the exposure of populations to PM10 and
      PM2.5 across municipal areas. We report on the practicalities of using a laser
      light scattering portable particulate monitor (Turnkey Instruments DustMate), in
      combination with a GPS, to map PM10 and PM2.5 concentrations on city-wide scales
      in Newcastle upon Tyne/Gateshead (UK), during a series of walking surveys. A
      heated inlet is necessary to remove moisture droplets from the sampled air prior
      to analysis by the instrument, though this also results in the loss of volatile
      particulate components, particularly from the PM2.5 fraction. A co-location
      calibration study was carried out with a reference urban background Tapered
      Element Oscillating Micro-Balance/Filter Dynamics Measuring System (TEOM-FDMS)
      system in Newcastle that is part of the UK's Automatic Urban and Rural Network
      (AURN) of air quality monitoring stations. For PM10, orthogonal regression of the
      DustMate against TEOM-FDMS data gave a slope and intercept of 1.02 +/- 0.06 and 
      3.7 +/- 1.2, respectively (R2 = 0.73), whereas for PM2.5, the respective values
      were 0.78 +/- 0.06 and -0.63 +/- 0.55 (R2 = 0.79). These parameters are
      comparable to literature calibration studies using this technology. There was
      good agreement between simultaneous samples taken using two DustMate instruments:
      for PM10, a slope and intercept of 1.05 +/- 0.03 and 0.36 +/- 0.5, respectively
      (R2 = 0.73), were obtained, whereas for the PM2.5, the respective values were
      0.79 +/- 0.01 and 0.19 +/- 0.06 (R2 = 0.86). Correction factors based on the
      slope and intercepts obtained from the calibration exercise were applied to raw
      data collected from the DustMate. An annually-normalised correction procedure was
      then used to account for different background particulate concentrations on
      different sampling days. These corrected PM10 and PM2.5 concentrations and
      corresponding GPS coordinates were displayed on a base map using Google Fusion
      Tables and Google Earth Professional. Almost all areas surveyed in
      Newcastle/Gateshead were well below the EU Air Quality Standards for PM10 and
      PM2.5.

PMID- 27867425
TI  - Gold nanoparticles for cancer radiotherapy: a review.
AB  - Radiotherapy is currently used in around 50% of cancer treatments and relies on
      the deposition of energy directly into tumour tissue. Although it is generally
      effective, some of the deposited energy can adversely affect healthy tissue
      outside the tumour volume, especially in the case of photon radiation (gamma and
      X-rays). Improved radiotherapy outcomes can be achieved by employing ion beams
      due to the characteristic energy deposition curve which culminates in a
      localised, high radiation dose (in form of a Bragg peak). In addition to ion
      radiotherapy, novel sensitisers, such as nanoparticles, have shown to locally
      increase the damaging effect of both photon and ion radiation, when both are
      applied to the tumour area. Amongst the available nanoparticle systems, gold
      nanoparticles have become particularly popular due to several advantages:
      biocompatibility, well-established methods for synthesis in a wide range of
      sizes, and the possibility of coating of their surface with a large number of
      different molecules to provide partial control of, for example, surface charge or
      interaction with serum proteins. This gives a full range of options for design
      parameter combinations, in which the optimal choice is not always clear,
      partially due to a lack of understanding of many processes that take place upon
      irradiation of such complicated systems. In this review, we summarise the
      mechanisms of action of radiation therapy with photons and ions in the presence
      and absence of nanoparticles, as well as the influence of some of the core and
      coating design parameters of nanoparticles on their radiosensitisation
      capabilities.

PMID- 27867428
TI  - A class of non-linear exposure-response models suitable for health impact
      assessment applicable to large cohort studies of ambient air pollution.
AB  - The effectiveness of regulatory actions designed to improve air quality is often
      assessed by predicting changes in public health resulting from their
      implementation. Risk of premature mortality from long-term exposure to ambient
      air pollution is the single most important contributor to such assessments and is
      estimated from observational studies generally assuming a log-linear, no
      threshold association between ambient concentrations and death. There has been
      only limited assessment of this assumption in part because of a lack of methods
      to estimate the shape of the exposure-response function in very large study
      populations. In this paper, we propose a new class of variable coefficient risk
      functions capable of capturing a variety of potentially non-linear associations
      which are suitable for health impact assessment. We construct the class by
      defining transformations of concentration as the product of either a linear or
      log-linear function of concentration multiplied by a logistic weighting function.
      These risk functions can be estimated using hazard regression survival models
      with currently available computer software and can accommodate large population
      based cohorts which are increasingly being used for this purpose. We illustrate
      our modeling approach with two large cohort studies of long-term concentrations
      of ambient air pollution and mortality: the American Cancer Society Cancer
      Prevention Study II (CPS II) cohort and the Canadian Census Health and
      Environment Cohort (CanCHEC). We then estimate the number of deaths attributable
      to changes in fine particulate matter concentrations over the 2000 to 2010 time
      period in both Canada and the USA using both linear and non-linear hazard
      function models.

PMID- 27867429
TI  - Correlation between Diastolic Function and Endothelial Function in Patients with
      Type 2 Diabetes and Hypertension.
AB  - BACKGROUND: Endothelial dysfunction may be involved in the pathophysiology of
      cardiac abnormalities in patients with diabetes mellitus (DM). A correlation
      between endothelial dysfunction and diastolic dysfunction in patients with type 1
      DM has been demonstrated, but this relationship has not been well investigated in
      type 2 DM. OBJECTIVE: Compare groups of patients with type 2 DM and hypertension
      with and without diastolic dysfunction using endothelial function indexes, and to
      assess whether correlations exist between the diastolic function and the
      endothelial function indexes. METHOD: This was a cross-sectional study of 34 men
      and women with type 2 DM and hypertension who were aged between 40 and 70 years
      and were categorized based on assessments of their Doppler echocardiographic
      parameters as having normal (14 patients) and abnormal (20 patients) diastolic
      function. Flow-mediated dilatation (FMD) assessments of the brachial artery
      evaluated the patients' endothelial function. RESULTS: The mean maximum FMD was
      7.15 +/- 2.80% for the patients with diastolic dysfunction and it was 11.85 +/-
      4.77% for the patients with normal diastolic function (p = 0.004). Correlations
      existed between the maximum FMD and the E/e' ratio (p = 0.040, r = -0.354) and
      the early wave velocity (e') at the lateral mitral annulus (p = 0.002, r =
      0.509). CONCLUSION: The endothelial function assessed by FMD was worse in
      hypertensive diabetic patients with diastolic dysfunction. There were
      correlations between the diastolic function indexes and the endothelial function
      indexes in our sample.

PMID- 27867430
TI  - Evaluation in Mouse Model of Combined Virus-bacterial Vaccine Based on Attenuated
      Influenza A(H7N3) Virus and the Group B Streptococcus Recombinant Polypeptides.
AB  - BACKGROUND: Secondary bacterial influenza complications are a common cause of
      excesses morbidity and mortality, which determines the need to develop means for
      specific prophylaxis. Group B streptococcal infection is especially common cause
      of pneumonia among children and the elderly with underlying conditions. Here we
      investigate in a mouse model the effects of combined intranasal immunization
      using live attenuated influenza vaccine and recombinant polypeptides based on
      group B Streptococcus surface proteins. METHODS: Groups of outbred mice received
      two doses of the following preparations: 1) the reassortant
      A/17/Mallard/Netherlands/00/95 (H7N3) influenza virus; 2) a mixture of P6, ScaAB,
      ScpB1 and Stv recombinant GBS proteins (20 ug total); 3) the A(H7N3) influenza
      vaccine pooled with the four bacterial peptide preparation; 4) control animals
      were treated with PBS. RESULTS: Intranasal vaccination using LAIV in combination
      with GBS polypeptides provided advantageous protection against infections with
      homologous A/Mallard/Netherlands/12/00 (H7N3) wild type virus or heterologous
      A/Puerto Rico/8/34 (H1N1) followed by serotype II GBS infection. Also, combined
      vaccination improved bacterial clearance from the lungs of mice. CONCLUSION:
      Intranasal immunization with LAIV+GBSV was safe and enabled to induce the
      antibody response to each of vaccine components. Thus, the combined vaccine
      increased the protective effect against influenza and its bacterial complications
      in mice compared to LAIV-only.

PMID- 27867431
TI  - The Avise Lupus Test and Cell-bound Complement Activation Products Aid the
      Diagnosis of Systemic Lupus Erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a multifaceted disease, and its
      diagnosis may be challenging. A blood test for the diagnosis of SLE, the Avise
      Lupus test, has been recently commercialized and validated in clinical studies.
      OBJECTIVES: To evaluate the use of the Avise Lupus test by community
      rheumatologists. METHODS: The study is a longitudinal, case-control,
      retrospective review of medical charts. Cases had a positive test result, and
      controls had a negative result; all patients were anti-nuclear antibodies (ANA)
      positive but negative for SLE-specific autoantibodies. Features of SLE,
      diagnosis, and medications at two time points were recorded. RESULTS: Twenty of
      the 23 cases (87%) and 4 of the 23 controls (17%) were diagnosed with SLE
      (sensitivity=83%; specificity=86%). More cases than controls (43% vs. 17%)
      fulfilled 4 American College of Rheumatology (ACR) classification criteria of
      SLE. Sensitivity of the test was significantly higher than the ACR score (83% vs.
      42%, p=0.006). A higher percentage of patients who met the classification
      criteria had elevated cell-bound complement activation products (CB-CAPs)
      compared to patients who did not. Anti-rheumatic medications were used in a
      higher percentage of cases than controls (83% vs. 35% at baseline, p=0.002),
      suggesting that cases were treated more aggressively early on. CONCLUSION: A
      positive Avise Lupus test result aids in formulating a SLE diagnosis when
      diagnosis based on standard-of-care tests and clinical features may be
      challenging, and impacts patient management. Prospective studies will be
      performed to better evaluate the clinical utility of the test and of CB-CAPs as
      biomarkers of SLE.

PMID- 27867432
TI  - Arthritis of the Knee Joint in Rheumatoid Arthritis - Evaluation of Treatment
      Response by Ultrasound in Daily Clinical Practice.
AB  - BACKGROUND: Rheumatoid arthritis (RA) commonly involves the knee joint in up to
      30% of patients. Musculoskeletal ultrasound enables the skilled clinician to
      easily assess disease activity. OBJECTIVE: To evaluate the sensitivity to change
      of the sonography score of large joints in Rheumatology (SOLAR) for different
      treatments of knee arthritis in RA. METHOD: Joints were assessed by ultrasound at
      4 visits. Laboratory, immunological and clinical parameters were recorded.
      RESULTS: 225 RA patients were analyzed. The DAS 28 in the subgroup receiving
      systemic steroids was significantly higher (p < 0.001) than in patients treated
      with intraarticular glucocorticosteroids (GCs) at T0, comparing the values from
      T0 to T3 the same appeared (p=0.003). Concerning the acute GC treatment regimens,
      the gray scale ultrasound (GSUS) sum score was found to be significantly higher
      in patients receiving intraarticular GCs versus no GCs (p=0,035), as well as in
      patients receiving systemic versus intraarticular GCs (p=0.001). Regarding the
      differences from T0 and T3, similar to the baseline analysis, a high GSUS sum
      score was significantly associated with intraarticular GCs, a low to no GC
      administration (p=0.035), while a high GSUS sum score was significantly linked to
      intraarticular GCs, rather than systemic GCs (p=0.008). CONCLUSION: SOLAR score
      is sensitive to change in knee arthritis. Intraarticular GC administration is
      performed in patients with high GSUS scores. Systemic administration of GC is
      linked to high disease activity (DAS28) rather than GSUS or power Doppler
      ultrasound (PDUS) results.

PMID- 27867433
TI  - Open-label Study of Initial and Repeat Treatment Cycles of Hylan G-F 20 in
      Patients with Symptomatic Knee Osteoarthritis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of initial and repeat treatment
      with hylan G-F 20 in patients with symptomatic osteoarthritis (OA) of the knee.
      METHODS: A prospective, multicenter, open-label study in adult patients with
      symptomatic knee OA (Kellgren-Lawrence grades I-III) undergoing repeat (SC group)
      or initial (IC group) treatment courses (3 x 2 mL of hylan G-F 20 at weekly
      intervals) was conducted with a maximum follow-up of 26 weeks. Reduction of pain
      using the Verbal Pain Questionnaire (VPQ) and Patient Global Assessment (PTGA)
      scores, concomitant pain medications use, and adverse events (AEs) were
      evaluated. RESULTS: A total of 842 patients were included (SC group, n=314; IC
      group, n=528), of whom 616 formed the intent-to-treat (ITT) population (SC group,
      n=235; IC group, n=381). Of the 462 patients with follow-up at week 26, 311
      (67.3%) were defined as responders. In the ITT population, VPQ scores decreased
      significantly at 26 weeks (p<0.001) compared with baseline. VPQ and PTGA scores
      decreased significantly (p<0.001) from baseline at all time points, without any
      significant changes in concomitant medication use. Twenty-four treatment-related
      AEs (TEAEs) were reported in 2.9% of patients, with most being mild or moderate
      in intensity and resolving without sequelae. CONCLUSION: Initial and repeat
      courses of hylan G-F 20 were effective with a favorable safety profile for knee
      OA. The large patient population and the study's pragmatic design suggest that
      these results could be replicated in routine clinical practice.

PMID- 27867434
TI  - Exploring the Neurocircuitry Underpinning Predictability of Threat in Soldiers
      with PTSD Compared to Deployment Exposed Controls.
AB  - BACKGROUND: Prior work examining emotional dysregulation observed in
      posttraumatic stress disorder (PTSD) has primarily been limited to fear-learning
      processes specific to anticipation, habituation, and extinction of threat. In
      contrast, the response to threat itself has not been systematically evaluated.
      OBJECTIVE: To explore potential disruption in fear conditioning neurocircuitry in
      service members with PTSD, specifically in response to predictable versus
      unpredictable threats. METHOD: In the current study, active-duty U.S. Army
      soldiers with (PTSD group; n = 38) and without PTSD (deployment-exposed controls;
      DEC; n = 40), participated in a fear-conditioning study in which threat
      predictability was manipulated by presenting an aversive unconditioned stimulus
      (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or
      UCS alone (i.e., unpredictable). Threat expectation, skin conductance response
      (SCR), and functional magnetic resonance imaging (fMRI) signal to predictable and
      unpredictable threats (i.e., UCS) were assessed. RESULTS: Both groups showed
      greater threat expectancy and diminished threat-elicited SCRs to predictable
      compared to unpredictable threat. Significant group differences were observed
      within the amygdala, hippocampus, insula, and superior and middle temporal gyri.
      Contrary to our predictions, the PTSD group showed a diminished threat-related
      response within each of these brain regions during predictable compared to
      unpredictable threat, whereas the DEC group showed increased activation.
      CONCLUSION: Although, the PTSD group showed greater threat-related diminution,
      hypersensitivity to unpredictable threat cannot be ruled out. Furthermore, pre
      trauma, trait-like factors may have contributed to group differences in
      activation of the neurocircuitry underpinning fear conditioning.

PMID- 27867436
TI  - Putamen Activation Represents an Intrinsic Positive Prediction Error Signal for
      Visual Search in Repeated Configurations.
AB  - We investigated fMRI responses to visual search targets appearing at locations
      that were predicted by the search context. Based on previous work in visual
      category learning we expected an intrinsic reward prediction error signal in the
      putamen whenever the target appeared at a location that was predicted with some
      degree of uncertainty. Comparing target appearance at locations predicted with
      50% probability to either locations predicted with 100% probability or
      unpredicted locations, increased activation was observed in left posterior
      putamen and adjacent left posterior insula. Thus, our hypothesis of an intrinsic
      prediction error-like signal was confirmed. This extends the observation of
      intrinsic prediction error-like signals, driven by intrinsic rather than
      extrinsic reward, to memory-driven visual search.

PMID- 27867437
TI  - Sero-prevalence and Correlates of Hepatitis B and C Co-infection Among HIV
      infected Individuals in Two Regional Hospitals in Cameroon.
AB  - BACKGROUND: Liver disease related to Hepatitis B (HBV) and C (HCV) infection has
      become a major cause of morbidity and mortality in HIV/AIDS patients. Data on the
      prevalence of HBV and HCV in Cameroon remains inconclusive. OBJECTIVE: We aimed
      to determine the sero-prevalence and correlates of Hepatitis markers in HIV/AIDS
      patients in two Regional Hospitals. METHODS: A cross-sectional study carried out
      from December 2014 to March 2015. HIV/AIDS patients aged 21 were included and
      above, receiving care at HIV treatment centres. Data was collected using a
      structured questionnaire. Blood samples were collected to screen for Hepatitis
      with HBsAg and anti HCV antibody rapid immunochromatographic test kits.
      Correlates of hepatitis were investigated by logistic regression. STATA was used
      for data analysis. RESULTS: We included 833 HIV/AIDS patients,78.8% (657) were
      female. Mean age was 44(SD 11) years. Prevalence of Hepatitis in general (total
      of two viral markers tested) was 8.9% (74/833), with 6.1% for HBsAg and 2.8% for
      Anti-HCV antibodies. From multivariate analysis, the likelihood of having
      hepatitis was independently increased by a history of surgical interventions [OR:
      1.82(1.06-3.14)], and of sexually transmitted infections [OR: 2.20(1.04-4.67)].
      CONCLUSION: Almost one in ten participants with HIV/AIDS attending the BRH and
      LRH tested positive for either HBsAg or anti HCV antibodies. Screening for HBV
      and HCV should therefore be integrated to the existing guidelines in Cameroon as
      it can influence management. More studies are needed to evaluate the extent of
      liver disease and magnitude of HIV suppression in hepatitis and HIV coinfection
      in this setting.

PMID- 27867438
TI  - Total Sleep Deprivation and Pain Perception during Cold Noxious Stimuli in
      Humans.
AB  - BACKGROUND AND AIMS: A substantial portion of the population suffers from chronic
      pain leading to significant health care costs and lost productivity. Loss of
      sleep duration and quality are widely reported in patients suffering from a
      variety of acute or chronic pain conditions. Conversely, sleep loss has been
      known to elevate pain perception; thus a potential bi-directional relationship
      exists between sleep deprivation and pain. To date, the majority of studies
      examining the relationship between experimentally induced pain and sleep loss
      have focused on the measurement of pain threshold. Additionally, despite evidence
      of sex differences in ratings of perceived pain, previous studies examining pain
      following sleep loss have not probed for sex differences. We examined the effects
      of 24-hour total sleep deprivation (TSD) on perceived pain during a 2-minute cold
      pressor test (CPT). We hypothesized that TSD would augment perceived pain and
      that women would demonstrate an elevated pain response compared to men. METHODS:
      Testing was carried out in 14 men and 13 women. All subjects reported to be
      nonsmokers with no history of cardiovascular disease, autonomic dysfunction,
      asthma, or diabetes. All female subjects were free of oral contraceptive use, and
      were tested during the early follicular phase of the menstrual cycle. Trial order
      was randomized and testing sessions (Normal sleep (NS) and TSD) were separated by
      approximately one month. Subjects immersed their left hand, up to the wrist, in
      an ice water bath (~1 degrees C), and perceived pain was recorded every 15
      seconds from a modified Borg scale (6-20 arbitrary units a.u.). RESULTS:
      Perceived pain responses during CPT were augmented following TSD (Delta1.2 a.u.;
      time * condition, p<0.05). The augmented pain response following TSD was noted
      when perceived pain was expressed as mean (NS Delta7.0+/-0.5 vs. TSD Delta8.2+/
      0.5 a.u.; p<0.05) or peak (NS Delta8.9+/-0.6 vs. TSD Delta10.2+/-0.5 a.u.;
      p<0.05) perceived pain. The effects of TSD on perceived pain were similar in both
      men and women (condition * time * sex, p>0.05). CONCLUSIONS AND IMPLICATIONS: We
      conclude that TSD significantly augments perceived pain during CPT, but this
      response was not sex dependent. These findings support emerging evidence that
      adequate sleep represents a relevant, and cost effective,
      preventative/therapeutic strategy to reduce self-perceived pain in both men and
      women.

PMID- 27867440
TI  - An Unusual Case of a Metallic Foreign Body per Urethra.
AB  - BACKGROUND: Foreign body in the lower urinary tract has a low incidence. Here we
      discuss a case of a safety pin within the bulbar urethra inserted by a young boy
      for sexual gratification, which was successfully removed under cysto
      urethroscopic guidance. CASE REPORT: Herein we present a case of a 14-year-old
      boy who presented with complaints of perineal pain and dysuria. On evaluation in
      detail and from clinical history, we came to know that he had inserted a safety
      pin within the urethra. Urine analysis revealed microscopic haematuria and few
      pus cells. X-ray of the pelvis and computerised tomography helped in confirming
      the presence of the safety pin within the urethra. CONCLUSIONS: The method of
      extraction of a foreign body per urethra depends on the size and shape of the
      foreign body. Cysto-urethroscopic removal is successful depending on the physical
      characteristics of the foreign body. It has the advantage of minimising
      urothelial trauma and also helps in assessing any previous mucosal injury or
      thickening. Psychological evaluation and counselling may help to prevent further
      such episodes.

PMID- 27867439
TI  - Evaluation of Head and Neck Paragangliomas by Computed Tomography in Patients
      with Pheochromocytoma-Paraganglioma Syndromes.
AB  - BACKGROUND: Hereditary head and neck paragangliomas (HNP) are very often
      associated with pheochromocytoma-paraganglioma syndromes, which are caused by
      mutations in genes encoding subunits of succinate dehydrogenase (SDHx) complex.
      The aim of this study was to determine the frequency and location of HNP among
      SDHx carriers. MATERIAL/METHODS: A total of 72 patients with SDHx mutations
      underwent computed tomography examinations of the head and neck. HNP were present
      in 44 (61.1%) out of 72 patients (31 SDHD, 11 SDHB, 2 SDHC); 113 HNP were found;
      the most common were carotid paragangliomas (59) and vagal paragangliomas (27).
      RESULTS: The HNP were statistically more frequent in carriers of SDHD mutations
      compared to carriers of SDHB mutations (72.1% vs. 43.5%, p=0.033). Multiple
      tumors more often occurred in patients with SDHD mutations 26/31 (83.9%) than in
      patients with SDHB mutations 6/11 (54.5%) p=0.05. There was a significant
      difference in the prevalence of carotid paragangliomas between patients with SDHB
      and SDHD mutations (7/11 [63.6%] vs. 30/31 [96.8%], respectively, p=0.004).
      Patients with SDHD mutations more often had carotid paragangliomas located on the
      left side than on the right side, as compared to SDHB mutations 25/31 (80.6%) vs.
      4/11 (36.4%), p=0.006. CONCLUSIONS: SDHx mutations predispose to multifocal and
      bilateral HNP. Carotid and vagal paragangliomas occurred most often. Patients
      with SDHD mutations are characterized by higher frequency of HNP than patients
      with SDHB mutations, which is mainly driven by higher frequency of carotid body
      tumors in patients with SDHD mutations. No difference in the frequency of head
      and neck paragangliomas in other locations was found.

PMID- 27867441
TI  - The Role of Computed Tomography in the Diagnostics of Diaphragmatic Injury After
      Blunt Thoraco-Abdominal Trauma.
AB  - BACKGROUND: Diaphragmatic injuries occur in 0.8-8% of patients with blunt trauma.
      The clinical diagnosis of diaphragmatic rupture is difficult and may be
      overshadowed by associated injuries. Diaphragmatic rupture does not resolve
      spontaneously and may cause life-threatening complications. The aim of this study
      was to present radiological findings in patients with diaphragmatic injury.
      MATERIAL/METHODS: The analysis of computed tomography examinations performed
      between 2007 and 2012 revealed 200 patients after blunt thoraco-abdominal trauma.
      Diaphragmatic rupture was diagnosed in 13 patients. Twelve of these patients had
      suffered traumatic injuries and underwent a surgical procedure that confirmed the
      rupture of the diaphragm. Most of diaphragmatic ruptures were left-sided (10)
      while only 2 of them were right-sided. In addition to those 12 patients there,
      another patient was admitted to the emergency department with left-sided
      abdominal and chest pain. That patient had undergone a blunt thoracoabdominal
      trauma 5 years earlier and complained of recurring pain. During surgery there was
      only partial relaxation of the diaphragm, without rupture. The most important
      signs of the diaphragmatic rupture in computed tomography include: segmental
      discontinuity of the diaphragm with herniation through the rupture, dependent
      viscera sign, collar sign and other signs (sinus cut-off sign, hump sign, band
      sign). RESULTS: In our study blunt diaphragmatic rupture occurred in 6% of cases
      as confirmed intraoperatively. In all patients, coronal and sagittal reformatted
      images showed herniation through the diaphragmatic rupture. In left-sided
      ruptures, herniation was accompanied by segmental discontinuity of the diaphragm
      and collar sign. In right-sided ruptures, predominance of hump sign and band sign
      was observed. Other signs were less common. CONCLUSIONS: The knowledge of the CT
      findings suggesting diaphragmatic rupture improves the detection of injuries in
      thoraco-abdominal trauma patients.

PMID- 27867442
TI  - The Slowly Enlarging Ventriculus Terminalis.
AB  - BACKGROUND: A cerebral spinal fluid (CSF) cavity within the conus medullaris has
      been described by the term ventriculus terminalis (VT) or the fifth ventricle.
      The finding of a VT on MRI imaging of the lumbar spine is often incidental but
      may be found in patients with low back pain or neuromuscular deficits. These
      lesions, when identified, are thought to regress or remain stable in terms of
      size, although some have been described to enlarge in the presence of post
      traumatic meningeal hemorrhages or deformities of the vertebral canal. CASE
      REPORT: We describe a case of a slowly growing VT in a patient with progressing
      lower limb weakness without any history or imaging findings of trauma or spinal
      canal abnormalities. CONCLUSIONS: We present an intriguing case of a slowly
      growing VT in a woman with progressive neurological symptoms. Surgical
      fenestration provided complete symptomatic relief and follow-up imaging two years
      after surgery demonstrated no evidence of recurrence. This, to our knowledge, is
      the first described case of a slowly enlarging VT independent of any other
      imaging findings.

PMID- 27867443
TI  - The Complexities of Accessing Care and Treatment: Understanding Alcohol Use by
      Aboriginal Persons Living with HIV and AIDS.
AB  - The role of alcohol in the transmission of HIV and access to health services for
      persons living with HIV/AIDS is relatively unexamined across the globe. Our
      team's community-based, mixed methods study examined both of these questions from
      the perspectives of Aboriginal persons living in Canada with HIV/AIDS (APHA) and
      service providers (SP). A bilingual national survey was undertaken with APHAs and
      SPs and the findings were followed up on in peer interviews. A complex
      relationship was identified between alcohol use, perceptions of alcohol use and
      access to services. Nearly half of APHAs surveyed reported that alcohol played a
      role in their becoming HIV positive. APHAs and SPs differed in their assessment
      of the impact of alcohol in the lives of Aboriginal persons once diagnosed, with
      a far greater proportion of SPs identifying it as problematic. Both SPs and APHAs
      associated the misuse of alcohol with diminished health. Nearly half of the APHAs
      surveyed shared they had been told they were drinking by a SP when they were not,
      while over one-third reported ever being denied services because of drinking when
      in fact they were not. Both SPs and APHAs identified physical health and
      discrimination as key reasons. Notwithstanding these results that point to
      shortcomings in service provision, the data also reveal that most APHAs are
      recieving care in which their choices are respected and from providers they
      trust. The findings point to the need for a nuanced strategy to solidify the
      strengths and address the shortcomings in APHA's service provision.

PMID- 27867444
TI  - The Indigenous Red Ribbon Storytelling Study: What does it mean for Indigenous
      peoples living with HIV and a substance use disorder to access antiretroviral
      therapy in Saskatchewan?
AB  - Indigenous peoples living with HIV are less likely than non-Indigenous peoples
      living with HIV to access antiretroviral therapy; however, there is not enough
      contextual information surrounding this issue. The Indigenous Red Ribbon
      Storytelling Study was conducted in part to examine how Indigenous peoples living
      with HIV construct and understand their experiences accessing antiretroviral
      therapy. Our study design was critical Indigenous qualitative research, using the
      Behavioral Model of Health Services Use and community-based participatory
      research approaches. The study was conducted in partnership with Indigenous and
      non-Indigenous organizations. Study participants were adults from two Canadian
      cities. The study methods included 20 individual and two Indigenous sharing
      circle interviews, six participant observation sessions, a short survey and
      thematic analysis. Accessing antiretroviral therapy within the context of living
      with a substance use disorder was an overarching theme. Indigenous peoples living
      with HIV felt they had to choose between living with their active substance use
      disorder and accessing antiretroviral therapy. They felt misunderstood as a
      person living with a substance use disorder and often felt coerced into using
      antiretroviral therapy. Despite these challenges, they persevered as Indigenous
      peoples living with HIV and a substance use disorder. Further research on
      antiretroviral therapy access among Indigenous peoples living with HIV and a
      substance use disorder, particularly from the perspective of health service
      providers, is needed.

PMID- 27867445
TI  - Research as Cultural Renewal: Applying Two-Eyed Seeing in a Research Project
      about Cultural Interventions in First Nations Addictions Treatment.
AB  - This article explores the application of two-eyed seeing in the first year of a
      three-year study about the effectiveness of cultural interventions in First
      Nations alcohol and drug treatment in Canada. Two-eyed seeing is recognized by
      Canada's major health research funder as a starting point for bringing together
      the strengths of Indigenous and Western ways of knowing. With the aim of
      developing a culture-based measurement tool, our team carried out an Indigenous
      centred research process with our interpretation of two-eyed seeing as a guiding
      principle. This enabled us to engage in a decolonizing project that prioritized
      Indigenous methodologies and ways of knowing and knowledge alongside those of
      Western science. By concentrating on Indigenous governance in the research
      process, our project supported efforts at Indigenous cultural renewal. Two
      illustrations are offered, our team's reconceptualization of Western derived
      understandings of data collection through Indigenous storytelling and our
      research grant timeframe with Indigenous knowledge gardening. This article
      contributes to the Indigenous research and policy literature which is lacking
      documentation about how Indigenous communities and research teams are benefitting
      from two-eyed seeing.

PMID- 27867446
TI  - "So far it's been choosing which side effects I want or I can deal with": A
      grounded theory of HIV treatment side effects among people living with HIV.
AB  - Despite the availability of new antiretroviral drugs and the simplification of
      treatment options, side effects continue to affect people living with HIV. In
      this paper, we present the findings of a grounded theory study designed to gain a
      critical understanding of the experience of side effects. Three main categories
      emerged from the data: the side effects, the experience, and the connections. The
      first category suggests that we need to change how we think about side effects in
      order to take into account the context in which they are experienced as well as
      the types and nature of side effects. The second category puts forward the idea
      that the experience of side effects is composed of three interrelated processes:
      becoming with, living with, and dealing with. Finally, the third category points
      to new connections that are formed with people, things and systems in the
      presence of side effects.

PMID- 27867449
TI  - Exploring the Potential of Indigenous Foods to Address Hidden Hunger: Nutritive
      Value of Indigenous Foods of Santhal Tribal Community of Jharkhand, India.
AB  - Traditional foods of indigenous communities can be explored as a sustainable
      means of addressing undernutrition. Our study aimed at identifying indigenous
      foods of the Santhal tribal community of Godda district of Jharkhand, India,
      assessing their nutritive value, and appraising their potential role in
      addressing hidden hunger. A cross-sectional survey using qualitative methods like
      focus group discussions with women of childbearing age (15-49 years), adult
      males, and elderly people was conducted for food identification. This was
      followed by taxonomic classification and quantitative estimate of nutritive value
      of the identified foods either in a certified laboratory or from secondary data.
      The community was well aware of the indigenous food resources in their
      environment. More than 100 different types of indigenous foods including a number
      of green leafy vegetables were identified. Taxonomic classification was available
      for 25 food items and an additional 26 food items were sent for taxonomic
      classification. Many indigenous foods (more than 50% of which were green leafy
      vegetables) were found to be rich sources of micronutrients like calcium, iron,
      vitamin A as beta carotene, and folate. Maximizing utilization of indigenous
      foods can be an important and sustainable dietary diversification strategy for
      addressing hidden hunger in this indigenous community.

PMID- 27867447
TI  - The Roles of School Readiness and Poverty-Related Risk for 6th Grade Outcomes.
AB  - Low-income students are at increased risk for grade retention and suspension,
      which dampens their chances of high school graduation, college attendance, and
      future success. Drawing from a sample of 357 children and their families who
      participated in the Chicago School Readiness Project, we examine whether greater
      exposure to cumulative poverty-related risk from preschool through 5th grade is
      associated with greater risk of student retention and suspension in 6th grade.
      Logistic regression results indicate that exposure to higher levels of cumulative
      risk across the elementary school years is associated with students' increased
      risk of retention in 6th grade, even after controlling for child school readiness
      skills and other covariates. Importantly, findings of the association between
      average cumulative risk exposure and student suspension are more complex; the
      role of poverty-related risk is reduced to non-significance once early indicators
      of child school readiness and other covariates are included in regression models.
      While, children's early externalizing behavior prior to kindergarten places
      children at greater risk of suspension 7 years later, children's higher levels of
      internalizing behaviors and early math skills are associated with significantly
      decreased risk of suspension in the 6th grade. Together, findings from the study
      suggest the complex ways that both early school readiness and subsequent exposure
      to poverty-related risk may both serve as compelling predictors of children's
      likelihood of "staying on track" academically in the 6th grade.

PMID- 27867448
TI  - Management Commitment to Safety, Teamwork, and Hospital Worker Injuries.
AB  - Although many studies link teamwork in health care settings to patient safety,
      evidence linking teamwork to hospital worker safety is lacking. This study
      addresses this gap by providing evidence linking teamwork perceptions in hospital
      workers to worker injuries, and further, finds a linkage between manager
      commitment to safety and teamwork. Organizational records of worker injuries and
      survey responses regarding management commitment to safety and teamwork from 446
      hospital workers within 42 work units in a multi-site hospital system were
      examined. Results underscored the particular importance of teamwork on worker
      injuries as well as the importance of management commitment to safety as relating
      to teamwork. To improve worker safety, organizational leaders and unit managers
      should work to maintain environments wherein teamwork can thrive.

PMID- 27867450
TI  - Preserving Patient Privacy When Sharing Same-Disease Data.
AB  - Medical and health data are often collected for studying a specific disease. For
      such same-disease microdata, a privacy disclosure occurs as long as an individual
      is known to be in the microdata. Individuals in same-disease microdata are thus
      subject to higher disclosure risk than those in microdata with different
      diseases. This important problem has been overlooked in data-privacy research and
      practice, and no prior study has addressed this problem. In this study, we
      analyze the disclosure risk for the individuals in same-disease microdata and
      propose a new metric that is appropriate for measuring disclosure risk in this
      situation. An efficient algorithm is designed and implemented for anonymizing
      same-disease data to minimize the disclosure risk while keeping data utility as
      good as possible. An experimental study was conducted on real patient and
      population data. Experimental results show that traditional reidentification risk
      measures underestimate the actual disclosure risk for the individuals in same
      disease microdata and demonstrate that the proposed approach is very effective in
      reducing the actual risk for same-disease data. This study suggests that privacy
      protection policy and practice for sharing medical and health data should
      consider not only the individuals' identifying attributes but also the health and
      disease information contained in the data. It is recommended that data-sharing
      entities employ a statistical approach, instead of the HIPAA's Safe Harbor
      policy, when sharing same-disease microdata.

PMID- 27867453
TI  - [Individual determinants of the Quebec electronic health record adoption].
AB  - AIM: The potential of electronic health records to improve effectiveness, safety
      and quality of health care has been shown in several previous studies. However
      healthcare professionals remain reticent as for its use, which limits its
      potential effect on the health care system. The present study aimed to evaluate
      physicians' perceptions towards the electronic health record of Quebec. METHODS:
      Based on a literature review of the factors affecting the adoption of information
      and communication technologies in general, and e-health in particular,
      questionnaire was developed. A total of 12 doctors who represent potential users
      of the Quebec electronic health record completed and returned the questionnaire.
      Afterwards we performed a thematic analysis of content which was followed by a
      theorisation of emerging concepts. RESULTS: Physicians' intention to adopt the
      Quebec electronic health record is positively influenced by perceived usefulness,
      perceived ease of use, demonstrability of the results, system's compatibility
      with practice, and computer self-efficacy. Conversely, resistance to change
      negatively influences physicians' adoption of the electronic health record.
      CONCLUSION: It is crucial to understand factors that influence the acceptance of
      the Quebec electronic health records to inform decision makers. This will allow
      identifying potential users' expectations and to adjust implementation strategies
      accordingly in order to favour a better integration of this technology into
      medical practices.

PMID- 27867451
TI  - Thioredoxin-Interacting Protein Mediates NLRP3 Inflammasome Activation Involved
      in the Susceptibility to Ischemic Acute Kidney Injury in Diabetes.
AB  - Kidney in diabetic state is more sensitive to ischemic acute kidney injury (AKI).
      However, the underlying mechanisms remain unclear. Herein, we examined the impact
      of diabetes mellitus on thioredoxin-interacting protein (TXNIP) expression and
      whether mediated NLRP3 activation was associated with renal ischemia/reperfusion-
      (I/R-) induced AKI. In an in vivo model, streptozotocin-induced diabetic rats
      showed higher susceptibility to I/R injury with increased TXNIP expression, which
      was significantly attenuated by resveratrol (RES) treatment (10 mg/kg
      intraperitoneal daily injection for 7 consecutive days prior to I/R induction).
      RES treatment significantly inhibited TXNIP binding to NLRP3 in diabetic rats
      subjected to renal I/R injury. Furthermore, RES treatment significantly reduced
      cleaved caspase-1 expression and production of IL-1beta and IL-18. In an in vitro
      study using cultured human kidney proximal tubular cell (HK-2 cells) in high
      glucose condition (HG, 30 mM) subjected to hypoxia/reoxygenation (H/R), HG
      combined H/R (HH/R) stimulated TXNIP expression which was accompanied by
      increased NLRP3 expression, ROS generation, caspase-1 activity and IL-1beta
      levels, and aggravated HK-2 cells apoptosis. All these changes were significantly
      attenuated by TXNIP RNAi and RES treatment. In conclusion, our results
      demonstrate that TXNIP-mediated NLRP3 activation through oxidative stress is a
      key signaling mechanism in the susceptibility to AKI in diabetic models.

PMID- 27867452
TI  - Renalase as a Novel Biomarker for Evaluating the Severity of Hepatic Ischemia
      Reperfusion Injury.
AB  - Hepatic ischemia-reperfusion (I/R) injury is a serious complication in clinical
      practice. However, no efficient biomarkers are available for the evaluation of
      the severity of I/R injury. Recently, renalase has been reported to be implicated
      in the I/R injury of various organs. This protein is secreted into the blood in
      response to increased oxidative stress. To investigate the responsiveness of
      renalase to oxidative stress, we examined the changes of renalase in cell and
      mouse models. We observed a significant increase of renalase expression in HepG2
      cells in a time- and dose-dependent manner when treated with H2O2. Renalase
      expression also increased significantly in liver tissues that underwent the
      hepatic I/R process. The increased renalase levels could be efficiently
      suppressed by antioxidants in vitro and in vivo. Furthermore, serum renalase
      levels were significantly increased in the mouse models and also efficiently
      suppressed by antioxidants treatment. The variation trends are consistent between
      renalase and liver enzymes in the mouse models. In conclusion, renalase is highly
      sensitive and responsive to oxidative stress in vitro and in vivo. Moreover,
      renalase can be detected in the blood. These properties make renalase a highly
      promising biomarker for the evaluation of the severity of hepatic I/R injury.

PMID- 27867454
TI  - Predictors for the Outcome of Aortic Regurgitation After Cardiac Surgery in
      Patients with Ventricular Septal Defect and Aortic Cusp Prolapse in Saudi
      Patients.
AB  - BACKGROUND AND AIM: Aortic valve (AV) prolapse and subsequent aortic
      regurgitation (AR) are two complications of ventricular septal defects (VSD) that
      are located close to or in direct contact with the AV. This finding is one of the
      indications for surgical VSD closure even in the absence of symptoms to protect
      the AV integrity. The goal of our study was to assess the outcome and to identify
      the predictors for improvement or progression of AR after surgical repair.
      MATERIALS AND METHODS: A retrospective study of all children with VSD and AV
      prolapse who underwent cardiac surgery at King Abdulaziz Cardiac Centre in Riyadh
      between July 1999 and August 2013. RESULTS: A total of 41 consecutive patients,
      operated for VSD with prolapsed AV, with or without AR, were reviewed. The
      incidence of AV prolapse in the study population was 6.8% out of 655 patients
      with VSD. Thirty-six (88%) patients had a perimembranous VSD, and four had doubly
      committed VSD. Only one patient had an outlet muscular VSD. Right coronary cusp
      prolapse was found in 38 (92.7%) patients. Preoperative AR was absent in five
      patients, mild or less in 25 patients, moderate in seven, and severe in four
      patients. Twenty-six patients showed improvement in the degree of AR after
      surgery (Group A), 14 patients showed no change in the degree of AR (Group B)
      while only one patient showed the progression of his AR after surgery. Those with
      absent AR before surgery remained with no AR after surgery. Improvement was found
      more in those with mild degree of AR preoperatively compared to those with
      moderate and severe AR. Female gender also showed a tendency to improve more as
      compared to male. CONCLUSION: Early surgical closure is advisable for patients
      with VSD and associated AV prolapse to achieve a better outcome after repair and
      to prevent progression of AR in future.

PMID- 27867455
TI  - Diagnostic Accuracy of Computed Tomography Angiography as Compared to
      Conventional Angiography in Patients Undergoing Noncoronary Cardiac Surgery.
AB  - OBJECTIVE: To compare the diagnostic accuracy of multi-slice computed tomography
      (MSCT) angiography with conventional angiography in patients undergoing major
      noncoronary cardiac surgeries. MATERIALS AND METHODS: We studied fifty major
      noncoronary cardiac surgery patients scheduled for invasive coronary angiography,
      29 (58%) female and 21 (42%) male. Inclusion criteria of the study were age of
      the patients >=40 years, having low or intermediate probability of coronary
      artery disease (CAD), left ventricular ejection fraction (LVEF) >35%, and patient
      giving informed consent for undergoing MSCT and conventional coronary
      angiography. The patients with LVEF <35%, high pretest probability of CAD, and
      hemodynamically unstable were excluded from the study. RESULTS: The diagnostic
      accuracy of CT coronary angiography was evaluated regarding true positive, true
      negative values. The overall sensitivity and specificity of CT angiography
      technique was 100% (95% confidence interval [CI]: 39.76%-100%) and 91.30% (95%
      CI: 79.21%-97.58%). The positive (50%; 95% CI: 15.70%-84.30%) and negative
      predictive values (100%; 95% CI: 91.59%-100%) of CT angiography were also fairly
      high in these patients. CONCLUSION: Our study suggests that this non-invasive
      technique may improve perioperative risk stratification in patients undegoing non
      cardiac surgery.

PMID- 27867457
TI  - A Heart Set in Stone: A Case of Extensive Cardiac Calcification.
AB  - Massive endocardial calcification is a rare entity. We describe a rare disease
      endomyocardial fibrosis associated with massive calcification of the left
      ventricle suspected on a chest X-ray and confirmed by echocardiography and
      computed tomography in an 18-year-old female presenting with breathlessness and
      congestive heart failure.

PMID- 27867456
TI  - Heart Failure in Children.
AB  - Heart failure (HF) in children differs from that in adults in many respects. The
      causes and clinical presentations may differ considerably among children of
      different age groups and between children and adults. The time of onset of HF
      holds the key to the etiological diagnosis. Clinical presentation of HF in
      younger children can be nonspecific requiring heightened degree of suspicion. The
      overall outcome with HF is better in children than in adults as HF in children is
      commonly due to structural heart disease and reversible conditions which are
      amenable to therapy. The principles of management include treatment of the cause,
      correction of any precipitating event, and treatment of systemic or pulmonary
      congestion. Though HF in adults has been the subject of extensive research and
      generation of evidence-based guidelines, there is a scarcity of evidence base in
      pediatric HF.

PMID- 27867458
TI  - Renal Subcapsular Hematoma Caused by Hydrophilic Guide Wire during Patent Ductus
      Arteriosus Closure.
AB  - Hydrophilic guide wire-associated renal subcapsular hematoma (RSH) during patent
      ductus arteriosus (PDA) closure is an extremely rare clinical condition. Herein,
      we present the case of a 16-year-old adolescent who suffered accidental
      hydrophilic 0.035-inch guide wire-related RSH during PDA closure. This RSH was
      diagnosed by computerized tomography and selective renal angiography. It was
      successfully treated by conservative treatment.

PMID- 27867459
TI  - Successful Treatment of Giant Left Subclavian Artery Pseudoaneurysm Abutting the
      Arch of the Aorta and Descending Aorta.
AB  - A 28-year-old woman presented with 3-month history of fever of unknown origin and
      progressively increasing cough. She was diagnosed with pulmonary tuberculosis on
      bronchial lavage cultures. A chest X-ray performed on follow-up showed a new
      opacity in the left apical area of the chest. Computed tomography scan of chest
      showed a large 10 cm pseudoaneurysm of the left subclavian artery 1 cm from its
      take off from the arch of the aorta. The pseudoaneurysm was approached through a
      left posterolateral thoracotomy and opened following a proximal and distal
      control. A 3 cm longitudinal defect was identified in the subclavian artery
      within its intrathoracic portion. This was debrided and repaired with an
      autologous pericardial patch. The patient had an uneventful recovery and remained
      well on follow-up.

PMID- 27867460
TI  - Percutaneous Dual-valve Intervention in a High-risk Patient with Severe Aortic
      and Mitral Stenosis.
AB  - Aortic stenosis is the most frequent and mitral stenosis is the least frequent
      native single-sided valve disease in Europe. Patients with the combination of
      severe symptomatic degenerative aortic and mitral stenosis are very rare.
      Guidelines for the treatment of heart valve diseases are clear for single-valve
      situations. However, there is no common agreement or recommendation for the best
      treatment strategy in patients with multiple valve disease and severe concomitant
      comorbidities. A 76-year-old female patient with the combination of severe
      degenerative symptomatic aortic and mitral stenosis and several comorbidities
      including severe obesity, who was found unsuitable surgical candidate by the
      heart team and unsuitable for two-time general anesthesia in the case of two-step
      single-valve percutaneous approach by anesthesiologists, underwent successful
      percutaneous dual-valve single-intervention (transcatheter aortic valve
      implantation and percutaneous mitral balloon commissurotomy). Percutaneous dual
      valve single-intervention is feasible in selected symptomatic high-risk patients.

PMID- 27867461
TI  - Transesophageal Echocardiography and Radiation-induced Damages.
AB  - The long-term sequelae of mantle therapy include, especially lung and cardiac
      disease but also involve the vessels and the organs in the neck and thorax (such
      as thyroid, aorta, and esophagus). We presented the case of 66-year-old female
      admitted for congestive heart failure in radiation-induced heart disease. The
      patient had undergone to massive radiotherapy 42 years ago for Hodgkin's disease
      (type 1A). Transesophageal echocardiography was performed unsuccessfully with
      difficulty because of the rigidity and impedance of esophageal walls. Our case is
      an extraordinary report of radiotherapy's latency effect as a result of dramatic
      changes in the structure of mediastinum, in particular in the esophagus, causing
      unavailability of a transesophageal echocardiogram.

PMID- 27867463
TI  - Narrative and Dialog.

PMID- 27867462
TI  - Ruptured Sinus of Valsalva.

PMID- 27867464
TI  - Rheumatic Fever and Rheumatic Heart Disease a Historical Perspective.

PMID- 27867465
TI  - Specification of the Myopathy Type may Influence the Management of Noncompaction.

PMID- 27867466
TI  - A training paradigm to enhance performance and safe use of an innovative
      neuroendovascular device.
AB  - Training has been important to facilitate the safe use of new devices designed to
      repair vascular structures. This paper outlines the generic elements of a
      training program for vascular devices and uses as an example the actual training
      requirements for a novel device developed for the treatment of bifurcation
      intracranial aneurysms. Critical elements of the program include awareness of the
      clinical problem, technical features of device, case selection, and use of a
      simulator. Formal proctoring, evaluation of the training, and recording the
      clinical outcomes complement these elements. Interventional physicians should
      embrace the merits of a training module to improve the user experience, and
      vendors, physicians, and patients alike should be aligned in the goal of device
      training to improve its success rate and minimize complications of the procedure.

PMID- 27867467
TI  - High-throughput monitoring of wild bee diversity and abundance via mitogenomics.
AB  - Bee populations and other pollinators face multiple, synergistically acting
      threats, which have led to population declines, loss of local species richness
      and pollination services, and extinctions. However, our understanding of the
      degree, distribution and causes of declines is patchy, in part due to inadequate
      monitoring systems, with the challenge of taxonomic identification posing a major
      logistical barrier. Pollinator conservation would benefit from a high-throughput
      identification pipeline.We show that the metagenomic mining and resequencing of
      mitochondrial genomes (mitogenomics) can be applied successfully to bulk samples
      of wild bees. We assembled the mitogenomes of 48 UK bee species and then shotgun
      sequenced total DNA extracted from 204 whole bees that had been collected in 10
      pan-trap samples from farms in England and been identified morphologically to 33
      species. Each sample data set was mapped against the 48 reference mitogenomes.The
      morphological and mitogenomic data sets were highly congruent. Out of 63 total
      species detections in the morphological data set, the mitogenomic data set made
      59 correct detections (93.7% detection rate) and detected six more species
      (putative false positives). Direct inspection and an analysis with species
      specific primers suggested that these putative false positives were most likely
      due to incorrect morphological IDs. Read frequency significantly predicted
      species biomass frequency (R2 = 24.9%). Species lists, biomass frequencies,
      extrapolated species richness and community structure were recovered with less
      error than in a metabarcoding pipeline.Mitogenomics automates the onerous task of
      taxonomic identification, even for cryptic species, allowing the tracking of
      changes in species richness and distributions. A mitogenomic pipeline should thus
      be able to contain costs, maintain consistently high-quality data over long time
      series, incorporate retrospective taxonomic revisions and provide an auditable
      evidence trail. Mitogenomic data sets also provide estimates of species counts
      within samples and thus have potential for tracking population trajectories.

PMID- 27867468
TI  - Demonstration and quantification of the redistribution and oxidation of carbon
      monoxide in the human body by tracer analysis.
AB  - Numerous studies have confirmed the role of endogenous carbon monoxide (CO) gas
      as a signal transmitter. However, CO is considered an intracellular transmitter,
      as no studies have demonstrated the redistribution of CO from the blood to tissue
      cells. Tracer analyses of 13CO2 production following 13CO gas inhalation
      demonstrated that CO is oxidized to carbon dioxide (CO2) in the body and that CO
      oxidation does not occur in the circulation. However, these results could not
      clearly demonstrate the redistribution of CO, because oxidation may have occurred
      in the airway epithelium. The objective of this study, therefore, was to
      definitively demonstrate and quantify the redistribution and oxidation of CO
      using time-course analyses of CO and 13CO2 production following 13CO-hemoglobin
      infusion. The subject was infused with 0.45 L of 13CO-saturated autologous blood.
      Exhaled gas was collected intermittently for 36 hours for measurement of minute
      volumes of CO/CO2 exhalation and determination of the 13CO2/12CO2 ratio. 13CO2
      production significantly increased from 3 to 28 hours, peaking at 8 hours. Of the
      infused CO, 81% was exhaled as CO and 2.6% as 13CO2. Identical time courses of
      13CO2 production following 13CO-hemoglobin infusion and 13CO inhalation refute
      the hypothesis that CO is oxidized in the airway epithelium and clearly
      demonstrate the redistribution of CO from the blood to the tissues. Quantitative
      analyses have revealed that 19% of CO in the circulating blood is redistributed
      to tissue cells, whereas 2.6% is oxidized there. Overall, these results suggest
      that CO functions as a systemic signal transmitter.

PMID- 27867469
TI  - Hyperbaric oxygen increases tissue-plasminogen activator-induced thrombolysis in
      vitro, and reduces ischemic brain damage and edema in rats subjected to
      thromboembolic brain ischemia.
AB  - Recent data have shown that normobaric oxygen (NBO) increases the catalytic and
      thrombolytic efficiency of recombinant tissue plasminogen activator (rtPA) in
      vitro, and is as efficient as rtPA at restoring cerebral blood flow in rats
      subjected to thromboembolic brain ischemia. Therefore, in the present study, we
      studied the effects of hyperbaric oxygen (HBO) (i) on rtPA-induced thrombolysis
      in vitro and (ii) in rats subjected to thromboembolic middle cerebral artery
      occlusion-induced brain ischemia. HBO increases rtPA-induced thrombolysis in
      vitro to a greater extent than NBO; in addition, HBO treatment of 5-minute
      duration, but not of 25-minute duration, reduces brain damage and edema in vivo.
      In line with the facilitating effect of NBO on cerebral blood flow, our findings
      suggest that 5-minute HBO could have provided neuroprotection by promoting
      thrombolysis. The lack of effect of HBO exposure of longer duration is discussed.

PMID- 27867470
TI  - Effect of sevoflurane anesthesia on the comprehensive mRNA expression profile of
      the mouse hippocampus.
AB  - Postoperative nausea and vomiting (PONV) is a common complication after general
      anesthesia. Recent studies suggested that the hippocampus is involved in PONV.
      Hypothesising that hippocampal dopaminergic neurons are related to PONV, we
      examined the comprehensive mRNA profile of the hippocampus, using a sevoflurane
      treated mouse model to confirm this. This study was conducted after approval from
      our institutional animal ethics committee, the Animal Research Center of Sapporo
      Medical University School of Medicine (project number: 12-033). Eight mice were
      assigned to two groups: a naive group and a sevoflurane group (Sev group). In the
      Sev group, four mice were anesthetised with 3.5% sevoflurane for 1 hour.
      Subsequently, mRNA was isolated from their hippocampal cells and RNA sequencing
      was performed on an Illumina HiSeq 2500 platform. Mapping of the quality
      controlled, filtered paired-end reads to mouse genomes and quantification of the
      expression levels of each gene were performed using R software. The Rtn4rl2 gene
      that encodes the Nogo receptor was the most up-regulated gene in the present
      study. The expression levels of dopamine receptor genes and the tachykinin gene
      were increased by sevoflurane exposure, while the genes related to serotonin
      receptors were not altered by sevoflurane exposure. The expression levels of LIM
      homeodomain-related genes were highly down-regulated by sevoflurane. These
      findings suggest that sevoflurane exposure induces dopaminergic stimulation of
      hippocampal neurons and triggers PONV, while neuronal inflammation caused by LIM
      homeodomain-related genes is down-regulated by sevoflurane.

PMID- 27867471
TI  - Commentary on: "Effect of sevoflurane anesthesia on the comprehensive mRNA
      expression profile of the mouse hippocampus": Postoperative nausea and vomiting
      conundrum: RNA-seq to the rescue.

PMID- 27867472
TI  - Correction: Cocktail treatment, a promising strategy to treat acute cerebral
      ischemic stroke?
AB  - [This corrects the article on p. 33 in vol. 6, PMID: 27826421.].

PMID- 27867473
TI  - The role of hydrogen sulfide in stroke.
AB  - Stroke is a kind of acute cerebrovascular disease characterized by the focal lack
      of neurological function, including ischemic stroke and hemorrhagic stroke. As
      society ages rapidly, stroke has become the second leading cause of disability
      and death, and also become the main threat to human health and life. In recent
      years, findings from increasing animal and clinical trials have supplied
      scientific evidences for the treatment of stroke. Hydrogen sulfide (H2S), which
      has always been seen as a toxic gas, now has been thought to be the third gaseous
      signaling molecule following nitric oxide and carbon monoxide. Accumulating
      evidences indicate that H2S plays an important role in stroke. Given that its
      neuroprotective effect is dose-dependent, only when its concentration is
      relatively low, H2S can yield the neuroprotection, while high dose may lead to
      neurotoxicity. All these study results suggest that H2S may offer a new promising
      application for the therapy of stroke. Here, our review will present the role of
      H2S in stroke from its mechanism to animal and clinical studies.

PMID- 27867475
TI  - Characteristics of exogenous carbon monoxide deliveries.
AB  - Carbon monoxide (CO) has long been considered an environmental pollutant and a
      poison. Exogenous exposure to amounts of CO beyond the physiologic level of the
      body can result in a protective or adaptive response. However, as a
      gasotransmitter, endogenous CO is important for multiple physiologic functions.
      To date, at least seven distinct methods of delivering CO have been utilized in
      animal and clinical studies. In this mini-review, we summarize the exogenous CO
      delivery methods and compare their advantages and disadvantages.

PMID- 27867474
TI  - Nitric oxide and hyperoxic acute lung injury.
AB  - Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to
      exposure to elevated oxygen partial pressure. HALI has been a concern in clinical
      practice with the development of deep diving and the use of normobaric as well as
      hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has
      been extensively studied, the findings are still controversial. Nitric oxide (NO)
      is an intercellular messenger and has been considered as a signaling molecule
      involved in many physiological and pathological processes. Although the role of
      NO in the occurrence and development of pulmonary diseases including HALI has
      been extensively studied, the findings on the role of NO in HALI are conflicting.
      Moreover, inhalation of NO has been approved as a therapeutic strategy for
      several diseases. In this paper, we briefly summarize the role of NO in the
      pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI.

PMID- 27867476
TI  - Hyperbaric oxygen therapy for traumatic brain injury: bench-to-bedside.
AB  - Traumatic brain injury (TBI) is a serious public health problem in the United
      States. Survivors of TBI are often left with significant cognitive, behavioral,
      and communicative disabilities. So far there is no effective
      treatment/intervention in the daily clinical practice for TBI patients. The
      protective effects of hyperbaric oxygen therapy (HBOT) have been proved in
      stroke; however, its efficiency in TBI remains controversial. In this review, we
      will summarize the results of HBOT in experimental and clinical TBI, elaborate
      the mechanisms, and bring out our current understanding and opinions for future
      studies.

PMID- 27867478
TI  - Theoretical considerations on the ultimate depth that could be reached by
      saturation human divers.
AB  - The occurrence of paroxysmal narcotic episodes including psychotic-like symptoms
      in divers participating to experimental deep diving programs with various gas
      mixtures has constituted, beyond the classical symptoms of the high-pressure
      neurological syndrome, the major limitation for deep diving. With the development
      of new saturation deep diving programs and experiments by the eastern nations,
      such as India and China, we believed that it is of interest to examine what could
      be the ultimate depth that could be reached by saturation human divers. Based on
      previous data and the critical volume model of inert gas narcosis, we propose
      that the ultimate depth for saturation diving could be around 1,000 m.

PMID- 27867477
TI  - Hyperbaric oxygen therapy in experimental and clinical stroke.
AB  - Stroke, which is defined as a neurologic deficit caused by sudden impaired blood
      supply, has been considered as a common cause of death and disability for
      decades. The World Health Organization has declared that almost every 5 seconds a
      new stroke occurs, placing immense socioeconomic burdens. However, the effective
      and available treatment strategies are still limited. Additionally, the most
      effective therapy, such as thrombolysis and stenting for ischemic stroke,
      generally requires a narrow therapeutic time window after the event. A large
      majority of patients cannot be admitted to hospital and receive these effective
      treatments for reperfusion timely. Hyperbaric oxygen therapy (HBOT) has been
      frequently applied and investigated in stroke since 1960s. Numerous basic and
      clinical studies have shown the beneficial efficacy for neurological outcome
      after stroke, and meanwhile many underlying mechanisms associated with
      neuroprotection have been illustrated, such as cerebral oxygenation promotion and
      metabolic improvement, blood-brain barrier protection, anti-inflammation and
      cerebral edema, intracranial pressure modulation, decreased oxidative-stress and
      apoptosis, increased vascular and neural regeneration. However, HBOT in human
      stroke is still not sufficiently evidence-based, due to the insufficient
      randomized double-blind controlled clinical studies. To date, there are no
      uniform criteria for the dose and session duration of HBOT in different strokes.
      Furthermore, the additional effect of HBOT combined with drugs and other
      treatment strategies are being investigated recently. Therefore, more
      experimental and clinical research is imperative to identify the mechanisms more
      clearly and to explore the best protocol of HBOT in stroke treatment.

PMID- 27867479
TI  - Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury
      following heart transplantation in rats.
AB  - Because inhaled carbon monoxide (CO) provides potent anti-inflammatory and
      antioxidant effects against ischemia reperfusion injury, we hypothesized that
      treatment of organ donors with inhaled CO would decrease graft injury after heart
      transplantation. Hearts were heterotopically transplanted into syngeneic Lewis
      rats after 8 hours of cold preservation in University of Wisconsin solution.
      Donor rats were exposed to CO at a concentration of 250 parts per million for 24
      hours via a gas-exposure chamber. Severity of myocardial injury was determined by
      total serum creatine phosphokinase and troponin I levels at three hours after
      reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was
      performed on the heart graft tissue prior to implantation. Recipients of grafts
      from CO-exposed donors had lower levels of serum troponin I and creatine
      phosphokinase; less upregulation of mRNA for interleukin-6, intercellular
      adhesion molecule-1, and tumor necrosis factor-alpha; and fewer infiltrating
      cells. Although donor pretreatment with CO altered the expression of 49 genes
      expressly represented on the array, we could not obtain meaningful data to
      explain the mechanisms by which CO potentiated the protective effects.
      Pretreatment with CO gas before organ procurement effectively protected cardiac
      grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac
      transplant model. A clinical report review indicated that CO-poisoned organ
      donors may be comparable to non-poisoned donors.

PMID- 27867480
TI  - Xenon protects left ventricular diastolic function during acute ischemia, less
      than ischemic preconditioning.
AB  - Anesthetics modify regional left ventricular (LV) dysfunction following
      ischemia/reperfusion but their effects on global function in this setting are
      less clear. Aim of this study was to test the hypothesis that xenon would limit
      global LV dysfunction as caused by acute anterior wall ischemia, comparable to
      ischemic preconditioning. In an open-chest model under thiopental anesthesia, 30
      pigs underwent 60-minute left anterior descending coronary artery occlusion,
      followed by 120 minutes of reperfusion. A xenon group (constant inhalation from
      previous to ischemia through end of reperfusion) was compared to control and
      ischemic preconditioning. Load-independent measures of diastolic function (end
      diastolic pressure-volume relation, time constant of relaxation) and systolic
      function (end-systolic pressure-volume relation, preload-recruitable stroke work)
      were determined. Heart rate, arterial pressure, cardiac output, and arterial
      elastance were recorded. Data were compared in 26 pigs. Ischemia impaired global
      diastolic but not systolic function in control, which recovered during
      reperfusion. Xenon limited and preconditioning abolished diastolic dysfunction
      during ischemia. Arterial pressure decreased during reperfusion while arterial
      elastance increased. Tachycardia and antero-septal wall edema during reperfusion
      were observed in all groups. In spite of ischemia of 40% of LV mass, global
      systolic function was preserved. Deterioration in global diastolic function was
      limited by xenon and prevented by preconditioning.

PMID- 27867481
TI  - Temporal variation in the response of tumors to hyperoxia with breathing carbogen
      and oxygen.
AB  - The effect of hyperoxygenation with carbogen (95% O2 + 5% CO2) and 100% oxygen
      inhalation on partial pressure of oxygen (pO2) of radiation-induced fibrosarcoma
      (RIF-1) tumor was investigated. RIF-1 tumors were innoculated in C3H mice, and
      aggregates of oximetry probe, lithium phthalocyanine (LiPc), was implanted in
      each tumor. A baseline tumor pO2 was measured by electron paramagnetic resonance
      (EPR) oximetry for 20 minutes in anesthetized mice breathing 30% O2 and then the
      gas was switched to carbogen or 100 % oxygen for 60 minutes. These experiments
      were repeated for 10 days. RIF-1 tumors were hypoxic with a baseline tissue pO2
      of 6.2-8.3 mmHg in mice breathing 30% O2. Carbogen and 100% oxygen significantly
      increased tumor pO2 on days 1 to 5, with a maximal increase at approximately 32
      45 minutes on each day. However, the extent of increase in pO2 from the baseline
      declined significantly on day 5 and day 10. The results provide quantitative
      information on the effect of hyperoxic gas inhalation on tumor pO2 over the
      course of 10 days. EPR oximetry can be effectively used to repeatedly monitor
      tumor pO2 and test hyperoxic methods for potential clinical applications.

PMID- 27867485
TI  - What's new in Medical Gas Research: Highlights for 2015.

PMID- 27867482
TI  - Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective.
AB  - Acute ischemic stroke is a common and serious neurological disease. Oxygen
      therapy has been shown to increase oxygen supply to ischemic tissues and improve
      outcomes after cerebral ischemia/reperfusion. Normobaric hyperoxia (NBO), an
      easily applicable and non-invasive method, shows protective effects on acute
      ischemic stroke animals and patients in pilot studies. However, many critical
      scientific questions are still unclear, such as the therapeutic time window of
      NBO, the long-term effects and the benefits of NBO in large clinic trials. In
      this article, we review the current literatures on NBO treatment of acute
      ischemic stroke in preclinical and clinical studies and try to analyze and
      identify the key gaps or unknowns in our understanding about NBO. Based on these
      analyses, we provide suggestions for future studies.

PMID- 27867483
TI  - Brain globins in physiology and pathology.
AB  - Globins are globular proteins for either transport or storage of oxygen which are
      critical for cellular metabolism. Four globins have been identified in rodent and
      human brains. Among them, neuroglobin, cytoglobin and hemoglobin chains are
      constitutively expressed in normal brain, while myoglobin is only expressed in
      some neurological disorders. Studies on the molecular structure, expression and
      functional features of these brain globins indicated that they may play crucial
      roles in maintenance of neural cell survival and activity, including neurons and
      astrocytes. Their regulation in neurological disorders may help thoroughly
      understand initiation and progression of ischemia, Alzheimer's disease and
      glioma, etc. Elucidation of the brain globin functions might remarkably improve
      medical strategies that sustain neurological homeostasis and treat neurological
      diseases. Here the expression pattern and functions of brain globins and their
      involvement in neurological disorders are reviewed.

PMID- 27867484
TI  - The production of high dose hydrogen gas by the AMS-H-01 for treatment of
      disease.
AB  - Hydrogen gas is a new and promising treatment option for a variety of diseases
      including stroke. Here, we introduce the AMS-H-01, a medically approved machine
      capable of safely producing ~66% hydrogen gas. Furthermore, we propose the
      significance of this machine in the future of hydrogen gas research.

PMID- 27867486
TI  - Effects of normobaric versus hyperbaric oxygen on cell injury induced by oxygen
      and glucose deprivation in acute brain slices.
AB  - Normobaric oxygen (NBO) and hyperbaric oxygen (HBO) are emerging as a possible co
      treatment of acute ischemic stroke. Both have been shown to reduce infarct
      volume, to improve neurologic outcome, to promote endogenous tissue plasminogen
      activator-induced thrombolysis and cerebral blood flow, and to improve tissue
      oxygenation through oxygen diffusion in the ischemic areas, thereby questioning
      the interest of HBO compared to NBO. In the present study, in order to
      investigate and compare the oxygen diffusion effects of NBO and HBO on acute
      ischemic stroke independently of their effects at the vascular level, we used
      acute brain slices exposed to oxygen and glucose deprivation, an ex vivo model of
      brain ischemia that allows investigating the acute effects of NBO (partial
      pressure of oxygen (pO2) = 1 atmospheres absolute (ATA) = 0.1 MPa) and HBO (pO2 =
      2.5 ATA = 0.25 MPa) through tissue oxygenation on ischemia-induced cell injury as
      measured by the release of lactate dehydrogenase. We found that HBO, but not NBO,
      reduced oxygen and glucose deprivation-induced cell injury, indicating that
      passive tissue oxygenation (i.e. without vascular support) of the brain
      parenchyma requires oxygen partial pressure higher than 1 ATA.

PMID- 27867487
TI  - Hypoxia therapy--a new hope for the treatment of mitochondrial dysfunctions.
AB  - Mitochondrial dysfunctions are characteristic features of numerous diseases and
      play a critical role in disease pathogenesis. Despite intensive research in this
      area, there are no approved therapies that directly target mitochondria. Recently
      a study by Jain et al. from Massachusetts General Hospital, USA reported the
      effectiveness of hypoxia for treatment of mitochondrial disease in mice. In this
      commentary, we summarized the potential mechanisms underlying the therapeutic
      effects of hypoxia on mitochondrial dysfunction, and clinical limitations of
      hypoxia as a therapy for human patients. We hope that our concerns will be
      helpful for further clinical studies addressing moderate hypoxia in mitochondrial
      dysfunction.

PMID- 27853502
TI  - Evolution of bright colours in animals: worlds of prohibition and oblivion.
AB  - Because the ability to hide in plain sight provides a major selective advantage
      to both prey and predator species, the emergence of the striking colouration of
      some animal species (such as many coral reef fish) represents an evolutionary
      conundrum that remains unsolved to date. Here I propose a framework by which
      conspicuous colours can emerge when the selective pressures for camouflage are
      relaxed (1) because camouflage is not essential under specific prey/predator
      conditions or (2) due to the impossibility of reducing the signal-to-background
      noise in the environment. The first case is found among non-predator-species that
      possess effective defences against predators (hence a "Carefree World"), such as
      the strong macaws' beaks and the flight abilities of hummingbirds. The second
      case is found in diurnal mobile fish of coral reef communities, which swim in
      clear waters against highly contrasting and unpredictable background (hence an
      "Hyper-Visible World"). In those contexts the selective pressures that usually
      come secondary to camouflage (such as sexual, warning, species recognition or
      territorial display) are free to drive the evolution of brilliant and diverse
      colouration. This theoretical framework can also be useful for studying the
      conditions that allow for conspicuousness in other sensory contexts (acoustic,
      chemical, electrical, etc.).

PMID- 27867488
TI  - Successful treatment with hydrogen rich water in a case of chronic graft-versus
      host-disease.
AB  - The incidence of chronic graft-versus-host-disease is rising year by year, which
      has become the leading cause of non-transplantation related death and has become
      the most difficult complication of allogeneic hematopoietic stem cell
      transplantation to deal with. Inflammation and fibrosis play dominant roles in
      the pathogenesis of chronic graft-versus-host-disease. Studies have shown that
      molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects.
      Therefore, we hypothesized that molecular hydrogen may have therapeutic effects
      on chronic graft-versus-host-disease. Here, we report a patient with severe
      chronic graft-versus-host-disease successfully treated by drinking hydrogen rich
      water which may be a safe and effective method for chronic graft-versus-host
      disease.

PMID- 27853504
TI  - Case Report: Microsurgical excision of grade 5 cerebral AVM.
AB  - In this case report, we discuss the microsurgical management of a Spetzler-Martin
      grade 5 arteriovenous malformation (AVM) in a young boy who presented with a
      hemorrhagic episode and had a high calculated risk of rebleeding. We also outline
      the rationale for choosing the management option.

PMID- 27853503
TI  - Adult attention-deficit/hyperactivity disorder: Associations between subtype and
      lifetime substance use - a clinical study.
AB  - ADHD is the one of the most prevalent childhood disorders and has been associated
      with impairments persisting into adulthood. Specifically, childhood ADHD is an
      independent clinical risk factor for the development of later substance use
      disorders (SUD). Moreover, adults who meet diagnostic criteria for ADHD have
      shown high rates of comorbid SUDs. Few studies, however, have reported on the
      relationship between ADHD subtypes and SUD in adult samples. The purpose of this
      study was to characterize a clinical sample of adults with ADHD and to identify
      possible associations between ADHD subtypes, lifetime substance use, and if ADHD
      subtypes may be preferentially associated with specific substances of abuse. We
      recruited 413 adult ADHD patients, performed an evaluation of their ADHD and
      conducted an interview on their use of psychotropic substances. Complete data was
      obtained for 349 patients. Lifetime substance abuse or dependence was 26% and
      occasional use was 57% in this sample. The inattentive subtype was significantly
      less likely to abuse or be dependent on cocaine than the combined subtype. Our
      findings underscore the high rate of comorbidity between substance use and ADHD
      in adults. The more frequent abuse/dependence of cocaine by adult patients with
      hyperactive-impulsive symptoms should be kept in mind when treating this patient
      group.

PMID- 27853510
TI  - CoNet app: inference of biological association networks using Cytoscape.
AB  - Here we present the Cytoscape app version of our association network inference
      tool CoNet. Though CoNet was developed with microbial community data from
      sequencing experiments in mind, it is designed to be generic and can detect
      associations in any data set where biological entities (such as genes,
      metabolites or species) have been observed repeatedly. The CoNet app supports
      Cytoscape 2.x and 3.x and offers a variety of network inference approaches, which
      can also be combined. Here we briefly describe its main features and illustrate
      its use on microbial count data obtained by 16S rDNA sequencing of arctic soil
      samples. The CoNet app is available at: http://apps.cytoscape.org/apps/conet.

PMID- 27853509
TI  - VISIT-TS: A multimedia tool for population studies on tic disorders.
AB  - Population-based assessment of Tourette syndrome (TS) and other tic disorders
      produces a paradox. On one hand, ideally diagnosis of tic disorders requires
      expert observation. In fact, diagnostic criteria for TS explicitly require expert
      assessment of tics for a definite diagnosis. On the other hand, large-scale
      population surveys with expert assessment of every subject are impracticable.
      True, several published studies have successfully used expert assessment to find
      tic prevalence in a representative population (e.g. all students in a school
      district). However, extending these studies to larger populations is daunting. We
      created a multimedia tool to demonstrate tics to a lay audience, discuss their
      defining and common attributes, and address features that differentiate tics from
      other movements and vocalizations. A first version was modified to improve
      clarity and to include a more diverse group in terms of age and ethnicity. The
      result is a tool intended for epidemiological research. It may also provide
      additional benefits, such as more representative minority recruitment for other
      TS studies and increased community awareness of TS.

PMID- 27853511
TI  - Molecular docking and molecular dynamics simulation study of inositol
      phosphorylceramide synthase - inhibitor complex in leishmaniasis: Insight into
      the structure based drug design.
AB  - Inositol phosphorylceramide synthase (IPCS) has emerged as an important,
      interesting and attractive target in the sphingolipid metabolism of Leishmania.
      IPCS catalyzes the conversion of ceramide to IPC which forms the most predominant
      sphingolipid in Leishmania. IPCS has no mammalian equivalent and also plays an
      important role in maintaining the infectivity and viability of the parasite. The
      present study explores the possibility of targeting IPCS; development of suitable
      inhibitors for the same would serve as a treatment strategy for the infectious
      disease leishmaniasis. Five coumarin derivatives were developed as inhibitors of
      IPCS protein. Molecular dynamics simulations of the complexes of IPCS with these
      inhibitors were performed which provided insights into the binding modes of the
      inhibitors. In vitro screening of the top three compounds has resulted in the
      identification of one of the compounds (compound 3) which shows little cytotoxic
      effects. This compound therefore represents a good starting point for further in
      vivo experimentation and could possibly serve as an important drug candidate for
      the treatment of leishmaniasis.

PMID- 27853512
TI  - Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually
      relevant hubs in biological networks.
AB  - : Highly connected nodes (hubs) in biological networks are topologically
      important to the structure of the network and have also been shown to be
      preferentially associated with a range of phenotypes of interest. The relative
      importance of a hub node, however, can change depending on the biological
      context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool
      (CHAT), which enables users to easily construct and visualize a network of
      interactions from a gene or protein list of interest, integrate contextual
      information, such as gene expression or mass spectrometry data, and identify hub
      nodes that are more highly connected to contextual nodes (e.g. genes or proteins
      that are differentially expressed) than expected by chance. In a case study, we
      use CHAT to construct a network of genes that are differentially expressed in
      Dengue fever, a viral infection. CHAT was used to identify and compare contextual
      and degree-based hubs in this network. The top 20 degree-based hubs were enriched
      in pathways related to the cell cycle and cancer, which is likely due to the fact
      that proteins involved in these processes tend to be highly connected in general.
      In comparison, the top 20 contextual hubs were enriched in pathways commonly
      observed in a viral infection including pathways related to the immune response
      to viral infection. This analysis shows that such contextual hubs are
      considerably more biologically relevant than degree-based hubs and that analyses
      which rely on the identification of hubs solely based on their connectivity may
      be biased towards nodes that are highly connected in general rather than in the
      specific context of interest. AVAILABILITY: CHAT is available for Cytoscape 3.0+
      and can be installed via the Cytoscape App Store (
      http://apps.cytoscape.org/apps/chat).

PMID- 27853513
TI  - South-East Asian strains of Plasmodium falciparum display higher ratio of non
      synonymous to synonymous polymorphisms compared to African strains.
AB  - Resistance to frontline anti-malarial drugs, including artemisinin, has
      repeatedly arisen in South-East Asia, but the reasons for this are not
      understood. Here we test whether evolutionary constraints on Plasmodium
      falciparum strains from South-East Asia differ from African strains. We find a
      significantly higher ratio of non-synonymous to synonymous polymorphisms in P.
      falciparum from South-East Asia compared to Africa, suggesting differences in the
      selective constraints on P. falciparum genome in these geographical regions.
      Furthermore, South-East Asian strains showed a higher proportion of non
      synonymous polymorphism at conserved positions, suggesting reduced negative
      selection. There was a lower rate of mixed infection by multiple genotypes in
      samples from South-East Asia compared to Africa. We propose that a lower mixed
      infection rate in South-East Asia reduces intra-host competition between the
      parasite clones, reducing the efficiency of natural selection. This might
      increase the probability of fixation of fitness-reducing mutations including drug
      resistant ones.

PMID- 27867497
TI  - Murine models of breast cancer bone metastasis.
AB  - Bone metastases cause significant morbidity and mortality in late-stage breast
      cancer patients and are currently considered incurable. Investigators rely on
      translational models to better understand the pathogenesis of skeletal
      complications of malignancy in order to identify therapeutic targets that may
      ultimately prevent and treat solid tumor metastasis to bone. Many experimental
      models of breast cancer bone metastases are in use today, each with its own
      caveats. In this methods review, we characterize the bone phenotype of commonly
      utilized human- and murine-derived breast cell lines that elicit osteoblastic
      and/or osteolytic destruction of bone in mice and report methods for optimizing
      tumor-take in murine models of bone metastasis. We then provide protocols for
      four of the most common xenograft and syngeneic inoculation routes for modeling
      breast cancer metastasis to the skeleton in mice, including the intra-cardiac,
      intra-arterial, orthotopic and intra-tibial methods of tumor cell injection.
      Recommendations for in vivo and ex vivo assessment of tumor progression and bone
      destruction are provided, followed by discussion of the strengths and limitations
      of the available tools and translational models that aid investigators in the
      study of breast cancer metastasis to bone.

PMID- 27867498
TI  - Bone muscle crosstalk targets muscle regeneration pathway regulated by core
      circadian transcriptional repressors DEC1 and DEC2.
AB  - Deletion of proprotein convertase Mbtps1 in bone osteocytes leads to a
      significant postnatal increase in skeletal muscle size and contractile function,
      while causing only a 25% increase in stiffness in long bones. Concerns about
      leakiness in skeletal muscle were discounted since Cre recombinase expression
      does not account for our findings, and, Mbtps1 protein and mRNA is not deleted.
      Interestingly, the response of normal skeletal muscle to exercise and the
      regenerative response of skeletal muscle to the deletion of Mbtps1 in bone share
      some key regulatory features including a preference for slow twitch muscle
      fibers. In addition, transcriptional regulators PPAR, PGC-1alpha, LXR, and
      repressors DEC1 and DEC2 all occupy central positions within these two pathways.
      We hypothesize that the age-dependent muscle phenotype in Dmp1-Cre Mbtps1 cKO
      mice is due to bone->muscle crosstalk. Many of the myogenic genes altered in this
      larger and functionally improved muscle are regulated by circadian core
      transcriptional repressors DEC1 and DEC2, and furthermore, display a temporal
      coordination with Dec1 and Dec2 expression consistent with a regulatory co
      dependency. These considerations lead us to propose that Dmp1-Cre Mbtps1 cKO
      osteocytes activate myogenesis by increased release of an activator of muscle
      PPAR-gamma, for example, PGE2 or sphingosine-1-P, or, by diminished release of an
      inhibitor of LXR, for example, long-chain polyunsaturated fatty acids. We hope
      that further investigation of these interacting pathways in the Dmp1-Cre Mbtps1
      cKO model will lead to clinically translatable findings applicable to age-related
      sarcopenia and other muscle wasting syndromes.

PMID- 27867499
TI  - Lessons on skeletal cell plasticity from studying jawbone regeneration in
      zebrafish.
AB  - Three major mesenchymal cell types have important roles in determining the shapes
      of vertebrate animals: bone-producing osteoblasts, cartilage-producing
      chondrocytes, and fat-producing adipocytes. Although often considered discrete
      cell types, accumulating evidence is revealing mesenchymal cells of intermediate
      identities and interconversion of cell types. Such plasticity is particularly
      evident during adult skeletal repair. In this Review, we highlight recent work in
      zebrafish showing a role for hybrid cartilage-bone cells in large-scale
      regeneration of the adult jawbone, as well as their origins in the periosteum. An
      emerging theme is that the unique mechanical and signaling environment of the
      adult wound causes skeletal cell differentiation to diverge from the discrete
      lineages seen during development, which may aid in rapid and extensive
      regeneration of bone.

PMID- 27867501
TI  - Challenging regulations: Managing risks in crop biotechnology.

PMID- 27867502
TI  - Genetics-based dynamic systems model of canopy photosynthesis: the key to improve
      light and resource use efficiencies for crops.
AB  - Improving canopy photosynthetic light use efficiency instead of leaf
      photosynthesis holds great potential to catalyze the next "green revolution".
      However, leaves in a canopy experience different biochemical limitations due to
      the heterogeneities of microclimates and also physiological parameters.
      Mechanistic dynamic systems models of canopy photosynthesis are now available
      which can be used to design the optimal canopy architectural and physiological
      parameters to maximize CO 2 uptake. Rapid development of modern crop genetics
      research now makes it possible to link such canopy models with genetic variations
      of crops to develop genetics-based dynamic systems models of canopy
      photosynthesis. Such models can guide marker-assisted breeding or genomic
      selection or engineering of crops to enhance light and nitrogen use efficiencies
      for different regions under future climate change scenarios.

PMID- 27867503
TI  - The CROPROTECT project and wider opportunities to improve farm productivity
      through web-based knowledge exchange.
AB  - A key global 21st century challenge is to maximize agricultural production while
      minimizing use of resources such as land, water, and energy to meet rising demand
      for produce. To meet this challenge, while also adapting to climate change,
      agriculture will have to become more knowledge intensive and deploy smarter
      farming techniques. The intention of this study was to: (1) Highlight the
      opportunity for web-based knowledge exchange to increase farm productivity and
      thus contribute to achieving food and energy security, (2) Give some examples of
      online farming information services such as the "CROPROTECT" tool I am developing
      in the UK, the CABI "Plantwise" Knowledge Bank and the IRRI "Rice Doctor," and
      (3) Consider lessons learnt so far. There are huge opportunities to facilitate
      knowledge exchange through online systems for farmers and people who advise
      farmers. CROPROTECT is interacting with users to determine priorities in terms of
      the pests, weeds, and diseases covered and is providing key information to assist
      with their management. Knowledge is a critical input for farming systems. Crop
      protection in particular is becoming more difficult due to evolution of pest
      resistance and changes in legislation. Up to date information can be made rapidly
      available and shared online through websites and smartphone Apps. Agricultural
      extension no longer relies solely on physical meetings and printed documents. The
      capacity to share information via the Internet is tremendous with its potential
      to reach a wide audience in the farming community, to provide rapid updates and
      to interact more with the users. However, in an era of information deluge,
      accessing relevant information and ensuring reliability are essential
      considerations. There is also a need to bring science and farming communities
      together to turn information into relevant farming knowledge.

PMID- 27867500
TI  - Neurological complications in chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) are frequently afflicted with
      neurological complications. These complications can potentially affect both the
      central and peripheral nervous systems. Common neurological complications in CKD
      include stroke, cognitive dysfunction, encephalopathy, peripheral and autonomic
      neuropathies. These conditions have significant impact not only on patient
      morbidity but also on mortality risk through a variety of mechanisms.
      Understanding the pathophysiological mechanisms of these conditions can provide
      insights into effective management strategies for neurological complications.
      This review describes clinical management of neurological complications in CKD
      with reference to the contributing physiological and pathological derangements.
      Stroke, cognitive dysfunction and dementia share several pathological mechanisms
      that may contribute to vascular impairment and neurodegeneration. Cognitive
      dysfunction and dementia may be differentiated from encephalopathy which has
      similar contributing factors but presents in an acute and rapidly progressive
      manner and may be accompanied by tremor and asterixis. Recent evidence suggests
      that dietary potassium restriction may be a useful preventative measure for
      peripheral neuropathy. Management of painful neuropathic symptoms can be achieved
      by pharmacological means with careful dosing and side effect considerations for
      reduced renal function. Patients with autonomic neuropathy may respond to
      sildenafil for impotence. Neurological complications often become clinically
      apparent at end-stage disease, however early detection and management of these
      conditions in mild CKD may reduce their impact at later stages.

PMID- 27867505
TI  - Personalised medicine and medicines optimisation.

PMID- 27867504
TI  - Short rotation plantations policy history in Europe: lessons from the past and
      recommendations for the future.
AB  - Short rotation plantations (SRPs) are fast-growing trees (such as willow (Salix
      spp.), poplar (Populus spp.) and Eucalyptus) grown closely together and harvested
      in periods of 2-20 years. There are around 50,000 hectares of SRPs in Europe, a
      relatively small area considering that there have been supportive policy measures
      in many countries for 30 years. This paper looks at the effect that the policy
      measures used in different EU countries have had, and how other external factors
      have impacted on the development of the industry. Rokwood was a 3-year European
      funded project which attempted to understand the obstacles and barriers facing
      the woody energy crops sector using well established methods of SWOT and PESTLE
      analysis. Stakeholder groups were formed in six different European regions to
      analyze the market drivers and barriers for SRP and propose ways that the
      industry could make progress through targeted research and development and an
      improved policy framework. Based upon the outcomes of the SWOT and PESTLE
      analysis, each region produced a series of recommendations for policymakers,
      public authorities, and government agencies to support the development,
      production, and use of SRP-derived wood fuel in each of the partner countries.
      This study provides details of the SRP policy analysis and reveals that each
      region shared a number of similarities with broad themes emerging. There is a
      need to educate farmers and policymakers about the multifunctional benefits of
      SRPs. Greater financial support from regional and/or national government is
      required in order to grow the SRP market. Introducing targeted subsidies as an
      incentive for growers could address lack of local supply chains. Long-term policy
      initiatives should be developed while increasing clarity within Government
      departments. Research funding should enable closer working between universities
      and industry with positive research findings developed into supportive policy
      measures.

PMID- 27867506
TI  - Independent validation of the Pain Management Plan in a multi-disciplinary pain
      team setting.
AB  - CONTEXT/BACKGROUND: The Pain Management Plan (PP) is a brief cognitive
      behavioural therapy (CBT) self-management programme for people living with
      persistent pain that can be individually facilitated or provided in a group
      setting. Evidence of PP efficacy has been reported previously by the pain centres
      involved in its development. OBJECTIVES: To provide a fully independent
      evaluation of the PP and compare these with the findings reported by Cole et al.
      METHODS: The PP programme was delivered by the County Durham Pain Team (Co.
      Durham PT) as outlined in training sessions led by Cole et al. Pre- and post
      quantitative/patient experience measures were repeated with reliable and clinical
      significant change determined and compared to the original evaluation. RESULTS:
      Of the 69 participants who completed the programme, 33% achieved reliable change
      and 20% clinical significant change using the Pain Self-Efficacy Questionnaire
      (PSEQ). Across the Brief Pain Inventory (BPI) interference domains between 11%
      and 22% of participants achieved clinical significant change. There were high
      levels of positive patient feedback with 25% of participants scoring 100%
      satisfaction. The mean participant satisfaction across the population was 88%.
      CONCLUSION: The results from this evaluation validate those reported by Cole et
      al. It demonstrates clinically significant improvement in pain and health
      functioning and high patient appreciation results. Both evaluations emphasise the
      potential of this programme as an early intervention delivered within a
      stratified care pain pathway. This approach could optimise the use of finite
      resources and improve wider access to pain management.

PMID- 27867507
TI  - Creating a better picture of chronic pain: improving pain pictogram designs
      through systematic evaluation of user responses.
AB  - This article discusses the challenges of visually representing pain qualities in
      pictogram design. An existing set of 12 pictograms designed for people with
      literacy problems was evaluated to understand more about misunderstandings of
      pictogram interpretation. Two sets of university students from different
      disciplines were asked to interpret the pictograms, and a novel classification
      system was developed to categorise answer types, as 'location', 'affective',
      temporal' or 'literal'. Several design recommendations are made as a result that
      will help improve the design of pain pictograms as a whole as well as guide
      designers of related pictogram work. We demonstrate how, through the robust
      classification of incorrect responses, it is possible to extract useful
      comprehension error patterns to inform future design.

PMID- 27867508
TI  - A feasibility study to determine the benefits of upper extremity virtual
      rehabilitation therapy for coping with chronic pain post-cancer surgery.
AB  - BACKGROUND: Persistent pain in shoulder and arm following post-surgical breast
      cancer treatment can lead to cognitive and physical deficits. Depression is also
      common in breast cancer survivors. Virtual reality therapy with integrative
      cognitive and physical rehabilitation has not been clinically trialed for this
      population. The novel BrightArm Duo technology improved cognition and upper
      extremity (UE) function for other diagnoses and has great potential to benefit
      individuals coping with post-surgical breast cancer pain. OBJECTIVES: The aim of
      this study was to explore the feasibility of BrightArm Duo therapy for coping
      with post-surgical chronic pain and associated disability in breast cancer
      survivors with depression. METHODS: BrightArm Duo is a robotic rehabilitation
      table modulating gravity loading on supported forearms. It tracks arm position
      and grasping strength while patients play three-dimensional (3D) custom
      integrative rehabilitation games. Community-dwelling women (N = 6) with post
      surgical breast cancer pain in the upper arm trained on the system twice a week
      for 8 weeks. Training difficulty increased progressively in game complexity,
      table tilt and session length (20-50 minutes). Standardized assessments were
      performed before and after therapy for pain, cognition, emotion, UE function and
      activities of daily living. RESULTS: Subjects averaged upwards of 1300 arm
      repetitions and 850 hand grasps per session. Pain intensity showed a 20% downward
      trend (p = 0.1) that was corroborated by therapist observations and participant
      feedback. A total of 10 out of 11 cognitive metrics improved post-training (p =
      0.01) with a significant 8.3-point reduction in depression severity (p = 0.04). A
      total of 17 of 18 range of motion metrics increased (p < 0.01), with five
      affected-side shoulder improvements above the Minimal Clinically Important
      Difference (8 degrees ). In all, 13 out of 15 strength and function metrics
      improved (p = 0.02) with lateral deltoid strength increasing 7.4 N on the
      affected side (p = 0.05). CONCLUSION: This pilot study demonstrated feasibility
      of using the BrightArm Duo Rehabilitation System to treat cancer survivors coping
      with upper body chronic pain. Outcomes indicate improvement in cognition,
      shoulder range, strength, function and depression.

PMID- 27867509
TI  - Comparison of fentanyl iontophoretic transdermal system and routine care with
      morphine intravenous patient-controlled analgesia in the management of early
      postoperative mobilisation: results from a randomised study.
AB  - INTRODUCTION: Fentanyl iontophoretic transdermal system (ITS) (IONSYS(r), The
      Medicines Company, Parsippany, NJ, USA) and morphine intravenous (IV) patient
      controlled analgesia (PCA) have demonstrated equivalent pain control in several
      published studies. The primary objective of the current study was to compare
      fentanyl ITS with morphine IV PCA with regard to the patient's ability to
      mobilise with acute postoperative pain. METHODS: In this multicentre, open-label,
      randomised, active-controlled, prospective phase IV study, postoperative patients
      initially received IV morphine and were titrated to pain score ? 4out of 10 on a
      Numeric Rating Scale (NRS) and then received fentanyl ITS (up to 240 ug (6
      doses)/hour; up to a maximum of 3.2 mg (80 doses)/24 hours) or morphine IV PCA
      (doses up to 20 mg morphine/2 hours, up to 240 mg/24 hours). The primary efficacy
      measure was ability to mobilise, assessed using patient responses to three
      validated questions regarding mobility on a 6-point Likert scale (0 = no
      difficulty to mobilise to 5 = a very great deal of difficulty to mobilise). The
      study was originally planned to include ~200 patients. However, following the
      early suspension and termination of the study, a total of 108 patients were
      randomised to study treatment. RESULTS: One hundred and eight patients were
      recruited prior to undergoing surgical procedures (orthopaedic surgical
      procedures (72%) or underwent major abdominal procedures (28%)). Postoperatively,
      58 were randomised to receive fentanyl ITS, and 50 to morphine IV PCA. Fentanyl
      ITS patients had a greater ability to mobilise at the time of stopping study
      drug, with an adjusted mean ability to mobilise score (95% confidence interval
      (CI)) of 0.14 (-0.19, 0.47) for fentanyl ITS patients and 2.37 (1.98, 2.76) for
      morphine IV PCA patients (p < 0.001). CONCLUSION: Patients treated with fentanyl
      ITS reported that they were better able to mobilise than patients treated with
      morphine IV PCA, at all time-points following surgery out to 24 hours.

PMID- 27867511
TI  - Is tapentadol different from classical opioids? A review of the evidence.
AB  - Tapentadol is a single molecule able to deliver analgesia by two distinct
      mechanisms, a feature which differentiates it from many other analgesics. Pre
      clinical data demonstrate two mechanisms of action: mu-opioid receptor agonist
      activity and noradrenaline re-uptake inhibition. From these, one may predict that
      tapentadol would be applicable across a broad spectrum of pain from nociceptive
      to neuropathic. The evidence in animal models suggests that norepinephrine re
      uptake inhibition (NRI) is a key mechanism and may even predominate over opioid
      actions in chronic (and especially neuropathic) pain states, reinforcing that
      tapentadol is different to classical opioids and may, therefore, be an a priori
      choice for the treatment of neuropathic and mixed pain. The clinical studies and
      subsequent practice experience and surveillance support the concept of opioid and
      non-opioid mechanisms of action. The reduced incidence of some of the typical
      opioid-induced side effects, compared to equianalgesic doses of classical
      opioids, supports the hypothesis that tapentadol analgesia is only partially
      mediated by opioid agonist mechanisms. Both the pre-clinical and clinical
      profiles appear to be differentiated from those of classical opioids.

PMID- 27867510
TI  - Effect of adding intrathecal morphine to a multimodal analgesic regimen for
      postoperative pain management after laparoscopic bariatric surgery: a
      prospective, double-blind, randomized controlled trial.
AB  - BACKGROUND: Pain control after bariatric surgery is a major challenge. Our
      objective was to study the efficacy and safety of intrathecal (IT) morphine 0.3
      mg added to bupivacaine 0.5% for postoperative pain after laparoscopic bariatric
      surgery. METHODS: After local ethics committee approval, 100 morbidly obese
      patients scheduled for laparoscopic bariatric surgery were enrolled in this
      study. Patients were randomly assigned into two groups: Group I received IT 0.3
      mg morphine (0.3 mL) added to 1.2 mL of bupivacaine 0.5%; Group II received IT
      0.3 mL saline added to 1.2 mL of bupivacaine 0.5%, immediately before induction
      of general anaesthesia. For both groups, 60 mg ketorolac and 1000 mg paracetamol
      were infused 30 minutes before the end of surgery. After wound closure, 20 mL
      bupivacaine 0.25% was infiltrated at wound edges. RESULTS: Visual Analogue Scale
      (VAS) score was significantly lower in group I immediately, 30 minutes and 1 hour
      postoperatively. Time to first ambulation, return of intestinal sounds and
      hospital stay were shorter in group I than group II (p < 0.05); total morphine
      consumption was significantly lower in group I than group II (p < 0.05). Sedation
      score was significantly higher in group I immediately postoperatively, while at
      30 minutes, 1, 2 and 6 hours postoperatively sedation scores were significantly
      higher in group II. Itching was significantly higher in group I. CONCLUSION: The
      addition of IT morphine to a multimodal analgesic regimen after laparoscopic
      bariatric surgery was an effective and safe method that markedly reduced
      postoperative pain, systemic opioid consumption and length of hospital stay.

PMID- 27867512
TI  - A service improvement project to review prescribing information provided by
      general practitioners for new referrals to a UK National Health Service hospital
      pain clinic: potential implications of CYP2D6 enzyme inhibition.
AB  - INTRODUCTION: Chronic pain is often managed using co-prescription of analgesics
      and adjuvants, with concomitant medication prescribed for comorbidities. Patients
      may have suboptimal response to some analgesics or be at risk of drug
      interactions or adverse drug reactions (ADRs) due to polypharmacy affecting
      CYP2D6 enzyme activity. The aim of the service improvement project was to
      determine the proportion of patients referred to a specialist pain service in the
      UK National Health Service (NHS) by general practitioners (GPs) who may be at
      risk of suboptimal analgesic response or ADRs due to CYP2D6 inhibition through
      polypharmacy. This was achieved by reviewing clinical prescribing information
      provided by GPs at time of referral. It was hoped that the findings could be used
      to aid clinical and prescribing decisions without conducting CYP2D6 genotyping or
      phenotyping. METHODS: A review of letters from 250 patients referred to an NHS
      hospital pain service from GPs over a 3-month period was undertaken. Information
      about current and concomitant medications was analysed to identify the potential
      for CYP2D6 inhibition and adverse events. RESULTS: Letters failed to provide
      information about current pain medication for 20 (8%) patients or non-pain
      concomitant medication for 54 (21.6%) patients. Of 176 patients, 52 (29.5%)
      patients with information about non-pain concomitant medication had been
      prescribed at least one known CYP2D6 inhibitor. A total of 35 (19.9%) patients
      were identified as being at risk of an adverse drug reaction and 33 (18.75%)
      patients at risk of suboptimal analgesic response due to co-administration of
      CYP2D6 inhibitors. CONCLUSION: The review revealed the need for improved detail
      in GP referral letters used to transfer care to UK NHS hospital pain clinics.
      There is a need to consider an individual's CYP2D6 phenotype when prescribing
      analgesic prodrugs to manage persistent pain. Caution is needed when patients are
      co-prescribed codeine or tramadol with selective serotonin reuptake inhibitors
      (SSRIs).

PMID- 27867513
TI  - Ultrasound-guided alcohol neurolysis of lateral femoral cutaneous nerve for
      intractable meralgia paresthetica: a case series.
AB  - Meralgia paresthetica is a rare sensory entrapment neuropathy which leads to
      burning, tingling and numbness in the antero-lateral aspect of thigh. Mostly it
      runs a benign course, and responds to conservative measures. We present a case
      series of six patients with intractable meralgia paresthetica with severe pain
      over antero-lateral thigh along the distribution of lateral cutaneous nerve of
      thigh which was further confirmed by nerve conduction study. These patients did
      not respond to the oral anti-neuropathic medications. The two successive
      diagnostic lateral femoral cutaneous nerve block not only had confirmed the
      diagnosis but also provided pain relief for a few days. Then the ultrasound
      guided lateral femoral cutaneous nerve neurolysis was done using 50% alcohol. In
      all the patients, there were more than 50% decrease in pain intensity and
      improvement in quality of life after the procedure, and the relief and
      improvement were maintained for up to 12 weeks. This case series shows ultrasound
      guided lateral femoral cutaneous nerve neurolysis is a safe and effective
      treatment for intractable meralgia paresthetica and also provides prolonged pain
      relief and is a good option in avoiding the surgery. Summary points The
      literature on neurolysis is rare, with only few case reports. This is the first
      case series on this topic, and it will greatly improve the evidence that
      ultrasound-guided neurolysis can also be used for intractable meralgia
      paresthetica patients who do not respond to conservative measures before
      proceeding to surgery.

PMID- 27867514
TI  - Hepatitis C virus drives the pathogenesis of hepatocellular carcinoma: from
      immune evasion to carcinogenesis.
AB  - Persistent hepatitis C virus (HCV) infection is associated with high incidence of
      hepatocellular carcinoma (HCC), the most common primary malignancy of the liver
      with over half a million new cases diagnosed annually worldwide. The aryl
      hydrocarbon receptor (AhR) is a ubiquitously expressed transcription factor and
      its activation by environmental chemicals and by its endogenous ligand kynurenine
      (Kyn) has been implicated in a variety of tumour-promoting processes such as
      transformation, tumorigenesis and in immunosuppression that enables tumour
      survival and growth. Kyn is generated constitutively by human tumour cells via
      tryptophan (Trp)-2,3-dioxygenase (TDO), a Trp-degrading enzyme expressed in
      liver, brain and cancer cells. Notably, it has been shown that TDO-derived Kyn
      suppresses anti-tumour immune responses, thus promoting tumour-cell survival
      through activation of the AhR pathway. In the context of HCV infection-associated
      HCC, it was shown that AhR signalling is increased in HCV-infected hepatocytes,
      and that modifications in the expression of AhR pathway-specific genes are
      associated with the progression of HCV infection into HCC. Based on these
      observations, we present and discuss here the hypothesis that HCV infection
      promotes HCC by modulation of the TDO-Kyn-AhR pathway, resulting in tumorigenesis
      as well as in suppression of both anti-HCV and anti-tumour immune responses.

PMID- 27867516
TI  - Autoantibodies against CD80 in patients with COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is an inflammation disorder and
      possibly an autoimmune disease. The components of the autoimmune response in the
      circulatory system are of considerable interest to clinicians. Because
      aberrations of costimulation status have been noted in COPD, the presence of
      autoantibodies to B7 costimulatory factor CD80 were investigated in a cohort of
      patients. Recombinant rs1CD80 (lacking the transmembrane domain of CD80) was used
      for Western blot analysis and ELISA to investigate the presence of autoantibodies
      in sera of patients with stable COPD and in controls without COPD. Cytokines IL-6
      and IL-8 were detected using ELISA. Western blot revealed a specific band
      reacting to rs1CD80 by diluting sera pool of patients, which indicated the
      existence of autoantibodies to CD80. The serum level of anti-rs1CD80 was higher
      in patients with COPD than in controls(P=0.0185) and was positively correlated to
      the serum level of IL-6 (r=0.797, P<0.001) and IL-8 (r=0.608, P<0.001). There was
      a tendency that more higher level of anti-rs1CD80, more severe COPD stage. The
      existence of autoantibodies to costimulatory factor CD80 may suggest a pathogenic
      role of costimulatory factors in COPD.

PMID- 27867515
TI  - The CD8 T-cell response during tolerance induction in liver transplantation.
AB  - Both experimental and clinical studies have shown that the liver possesses unique
      tolerogenic properties. Liver allografts can be spontaneously accepted across
      complete major histocompatibility mismatch in some animal models. In addition,
      some liver transplant patients can be successfully withdrawn from
      immunosuppressive medications, developing 'operational tolerance'. Multiple
      mechanisms have been shown to be involved in inducing and maintaining alloimmune
      tolerance associated with liver transplantation. Here, we focus on CD8 T-cell
      tolerance in this setting. We first discuss how alloreactive cytotoxic T-cell
      responses are generated against allografts, before reviewing how the liver
      parenchyma, donor passenger leucocytes and the host immune system function
      together to attenuate alloreactive CD8 T-cell responses to promote the long-term
      survival of liver transplants.

PMID- 27867518
TI  - Analyzing heterogeneity in the effects of physical activity in children on social
      network structure and peer selection dynamics.
AB  - BACKGROUND: Social networks influence children and adolescents' physical
      activity. The focus of this paper is to examine the differences in the effects of
      physical activity on friendship selection, with eye to the implications on
      physical activity interventions for young children. Network interventions to
      increase physical activity are warranted but have not been conducted. Prior to
      implementing a network intervention in the field, it is important to understand
      potential heterogeneities in the effects that activity level have on network
      structure. In this study, the associations between activity level and cross
      sectional network structure, and activity level and change in network structure
      are assessed. METHODS: We studied a real-world friendship network among 81
      children (average age 7.96 years) who lived in low SES neighborhoods, attended
      public schools, and attended one of two structured aftercare programs, of which
      one has existed and the other was new. We used the exponential random graph model
      (ERGMs) and its longitudinal extension to evaluate the association between
      activity level and various demographic factors in having, forming, and dissolving
      friendship. Due to heterogeneity between the friendship networks within the
      aftercare programs, separate analyses were conducted for each network. RESULTS:
      There was heterogeneity in the effect of physical activity on both cross
      sectional network structure and the formation and dissolution processes, both
      across time and between networks. CONCLUSIONS: Network analysis could be used to
      assess the unique structure and dynamics of a social network before an
      intervention is implemented, so as to optimize the effects of the network
      intervention for increasing childhood physical activity. Additionally, if peer
      selection processes are changing within a network, a static network intervention
      strategy for childhood physical activity could become inefficient as the network
      evolves.

PMID- 27867520
TI  - Consent information leaflets - readable or unreadable?
AB  - OBJECTIVE: The objective of this article is to assess the readability of leaflets
      about urological procedures provided by the British Association of Urological
      Surgeons (BAUS) to evaluate their suitability for providing information. METHODS:
      Information leaflets were assessed using three measures of readability: Flesch
      Reading Ease, Flesch-Kincaid and Simple Measure of Gobbledygook (SMOG) grade
      formulae. The scores were compared with national literacy statistics. RESULTS:
      Relatively good readability was demonstrated using the Flesch Reading Ease (53.4
      60.1) and Flesch-Kincaid Grade Level (6.5-7.6) methods. However, the average SMOG
      index (14.0-15.0) for each category suggests that the majority of the leaflets
      are written above the reading level of an 18-year-old. Using national literacy
      statistics, at least 43% of the population will have significant difficultly
      understanding the majority of these leaflets. CONCLUSIONS: The results suggest
      that comprehension of the leaflets provided by the BAUS is likely to be poor.
      These leaflets may be used as an adjunct to discussion but it is essential to
      ensure that all the information necessary to make an informed decision has been
      conveyed in a way that can be understood by the patient.

PMID- 27867519
TI  - Force-plate analyses of balance following a balance exercise program during acute
      post-operative phase in individuals with total hip and knee arthroplasty: A
      randomized clinical trial.
AB  - OBJECTIVES: Typical rehabilitation programs following total hip arthroplasty and
      total knee arthroplasty include joint range of motion and muscle-strengthening
      exercises. Balance and balance exercises following total hip arthroplasty and
      total knee arthroplasty have not received much attention. The purpose of this
      study was to determine whether an intervention of balance exercises added to a
      typical rehabilitation program positively affects patients' balance. METHODS: A
      total of 63 patients were provided with outpatient physical therapy at their
      home. Patients were randomly assigned to either typical (n = 33) or balance (n =
      30) exercise group. The typical group completed seven typical surgery-specific
      joint range of motion and muscle-strengthening exercises, while the balance group
      completed the typical exercises plus three balance exercises. After 5 weeks of
      administering the rehabilitation program, patients' balance was assessed on a
      force plate using 95% ellipse area of the center of pressure amplitude. RESULTS:
      Patients in the balance group demonstrated significant reduction in the 95%
      ellipse area for the anterior and posterior lean standing conditions (p < 0.01).
      CONCLUSION: Balance exercises added to the typical outpatient physical therapy
      program resulted in significantly greater improvements in balance for
      participants with total hip arthroplasty or total knee arthroplasty, compared to
      the typical exercise program alone. Physical therapists might consider the use of
      balance exercises to improve balance in individuals in the acute post-operative
      phase following total hip arthroplasty or total knee arthroplasty.

PMID- 27867517
TI  - Protective immunity to liver-stage malaria.
AB  - Despite decades of research and recent clinical trials, an efficacious long
      lasting preventative vaccine for malaria remains elusive. This parasite infects
      mammals via mosquito bites, progressing through several stages including the
      relatively short asymptomatic liver stage followed by the more persistent cyclic
      blood stage, the latter of which is responsible for all disease symptoms. As the
      liver acts as a bottleneck to blood-stage infection, it represents a potential
      site for parasite and disease control. In this review, we discuss immunity to
      liver-stage malaria. It is hoped that the knowledge gained from animal models of
      malaria immunity will translate into a more powerful and effective vaccine to
      reduce this global health problem.

PMID- 27867521
TI  - Exome-first approach identified a novel gloss deletion associated with Lowe
      syndrome.
AB  - Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and
      kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We
      report a 6-month-old male clinically suspected to have LS, but without the
      Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach,
      LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25
      q26.1, encompassing the entire OCRL gene and neighboring loci.

PMID- 27867522
TI  - Study protocol - A systematic review and meta-analysis of hypothermia in
      experimental traumatic brain injury: Why have promising animal studies not been
      replicated in pragmatic clinical trials?
AB  - Traumatic brain injury (TBI) is a major cause of death and permanent disability.
      Systemic hypothermia, a treatment used in TBI for many decades, has recently been
      found to be associated with neutral or unfavourable clinical outcomes despite
      apparently promising preclinical research. Systematic review and meta-analysis is
      a tool to summarize literature and observe trends in experimental design and
      quality that underpin its general conclusions. Here we aim to use these
      techniques to describe the use of hypothermia in animal TBI models, collating
      data relating to outcome and both study design and quality. From here we intend
      to observe correlations between features and attempt to explain any discrepancies
      found between animal and clinical data. This protocol describes the relevant
      methodology in detail.

PMID- 27867524
TI  - Varying effects of recommended treatments for heart failure with reduced ejection
      fraction: meta-analysis of randomized controlled trials in the ESC and ACCF/AHA
      guidelines.
AB  - The aim of this paper is to evaluate the treatment effects of recommended drugs
      and devices on key clinical outcomes for patients with heart failure with reduced
      ejection fraction (HFREF). Randomized controlled trials (RCTs) listed in the 2012
      HF guideline from the European Society of Cardiology as well as the 2013 HF
      guideline from the American College of Cardiology Foundation and American Heart
      Association were evaluated for use in the meta-analysis. RCTs written in English
      evaluating recommended drugs and devices for the treatment of patients with HFREF
      were included. Meta-analyses, based on the outcomes of all-cause mortality and
      hospitalization because of HF, were performed with relative risk ratio as the
      effect size. In the identified 47 RCTs, patients were on average 63 years old and
      22% were female. Drugs targeting the renin-angiotensin-aldosterone system, beta
      blockers, cardiac resynchronization therapy (CRT), and intracardiac defibrillator
      devices (ICDs) significantly reduced the risk of death with reductions of 14-19,
      23, 20, and 20%, respectively. Drugs targeting the renin-angiotensin-aldosterone
      system, beta-blockers, digoxin, and CRT significantly reduced the risk of HF
      hospitalization with reductions of 24-37, 22, 60, and 36%, respectively, while
      ICDs significantly increased the risk with 34%. Ivabradine showed no significant
      effects on either outcome. As such, the majority of recommended HFREF treatments
      offered significant treatment benefits. However, many of the included studies
      were from the 1990s or earlier, and one must therefore be cautious when
      extrapolating these results to contemporary patients with HF.

PMID- 27867523
TI  - Obesity paradox in heart failure: a heavy matter.
AB  - Obesity and heart failure are two of the leading causes of morbidity and
      mortality in the world. The relationship between obesity and cardiovascular
      diseases is complex and not fully understood. While the risk of developing heart
      failure has been shown to be higher in patients who are obese, there is a
      survival advantage for obese and overweight patients compared with normal weight
      or low weight patients. This phenomenon was first described by Horwich et al. and
      was subsequently confirmed in other large trials. The advantage exists
      irrespective of the type, aetiology, or stage of heart failure. Patients with
      morbid obesity (body mass index >40 kg/m2), however, do not have the same
      survival advantage of their obese counterparts. There are several alternative
      indices of obesity available that may be more accurate than body mass index. The
      role of weight loss in patients with heart failure is unclear; thus, providing
      sound clinical advice to patients remains difficult. Future prospective trials
      designed to evaluate the link between obesity and heart failure will help us
      understand more fully this complex relationship.

PMID- 27867525
TI  - Barriers to goals of care discussions with hospitalized patients with advanced
      heart failure: feasibility and performance of a novel questionnaire.
AB  - AIMS: Good end-of-life communication and decision-making are important to
      patients with advanced heart failure (HF) and their families, but their needs
      remain unmet. In this pilot study, we describe the feasibility and performance of
      a novel questionnaire aimed at identifying barriers and solutions to improve
      communication and decision-making about goals of care for hospitalized patients
      with advanced HF. METHODS: We distributed questionnaires to staff cardiologists,
      cardiology trainees, and cardiology nurses who provide care for HF patients at a
      Canadian teaching hospital. The questionnaire asked about the importance of
      various barriers to goals of care discussions. It also asked participants to rank
      their willingness to engage in goals of care discussions and their views on other
      clinicians could engage in such discussions. RESULTS: Of 76 clinicians, 44 (58%)
      completed the questionnaire (median completion time, 17 min). Individual survey
      questions had few missing responses (0% to 2%) for questions about barriers to
      goals of care discussions. There was appreciable discrimination of the importance
      of different barriers (mean scores 2.2 to 6.0 on a 7-point scale). Preliminary
      data suggest that clinicians perceive patient and family factors, such as
      difficulty accepting a poor prognosis, as the most important barriers preventing
      goals of care discussions. CONCLUSIONS: In this pilot study, we have demonstrated
      the feasibility of a novel questionnaire to be used in a larger multi-centre
      study of end-of-life HF care. Essential information will be obtained to inform
      the design and evaluation of interventions that seek to improve communication and
      decision-making about goals of care with HF patients.

PMID- 27867526
TI  - Characteristics of patients with haematological and breast cancer (1996-2009) who
      died of heart failure-related causes after cancer therapy.
AB  - AIMS: To describe the characteristics and time to death of patients with breast
      or haematological cancer who died of heart failure (HF) after cancer therapy.
      Patients with an index admission for HF who died of HF-related causes (IAHF) and
      those with no index admission for HF who died of HF-related causes (NIAHF) were
      compared. METHODS AND RESULTS: We performed a linked data analysis of cancer
      registry, death registry, and hospital administration records (n = 15 987). Index
      HF admission must have occurred after cancer diagnosis. Of the 4894 patients who
      were deceased (30.6% of cohort), 734 died of HF-related causes (50.1% female) of
      which 279 (38.0%) had at least one IAHF (41.9% female) post-cancer diagnosis.
      Median age was 71 years [interquartile range (IQR) 62-78] for IAHF and 66 years
      (IQR 56-74) for NIAHF. There were fewer chemotherapy separations for IAHF
      patients (median = 4, IQR 2-9) compared with NIAHF patients (median = 6, IQR 2
      12). Of the IAHF patients, 71% had died within 1 year of the index HF admission.
      There was no significant difference in HF-related mortality in IAHF patients
      compared with NIAHF (HR, 1.10, 95% CI, 0.94-1.29, P = 0.225). CONCLUSIONS: The
      profile of IAHF patients who died of HF-related causes after cancer treatment
      matched the current profile of HF in the general population (over half were aged
      >=70 years). However, NIAHF were younger (62% were aged <=69 years), female
      patients with breast cancer that died of HF-related causes before hospital
      admission for HF-related causes-a group that may have been undiagnosed or
      undertreated until death.

PMID- 27867528
TI  - Age- and sex-related differences in diastolic function and cardiac dimensions in
      a hypertensive population.
AB  - AIMS: The prevalence of left ventricular diastolic dysfunction increases with
      age, particularly in hypertensive women. We aimed to determine the age- and sex
      related differences in diastolic function, and its relation to alterations of
      cardiac dimensions in a hypertensive population. METHODS AND RESULTS: We enrolled
      479 hypertensive patients with a left ventricular ejection fraction (LVEF) >=50%
      (men/women, 267/212) and their echocardiographic parameters regarding LV
      performance and vascular function were measured. Left atrial volume index (LAVI)
      and operant diastolic elastance (EdI: E/e'/stroke volume index), but not LV mass
      index (LVMI), correlated weakly with age in both sexes. The arterial elastance
      index (EaI) and EdI did not differ significantly between sexes in any of the
      three age groups (A, <65 years; B, >=65 years but <75 years; C, age >=75 years).
      The EdI indexed to EaI, EdI/EaI = E/e'/(0.9 * systolic blood pressure), was
      significantly more impaired in women than in men only in group C. There were
      significant differences in LAVI, LVMI, and EdI/EaI between groups B and C only in
      women. CONCLUSIONS: Impairment of diastolic function relative to arterial
      elasticity, EdI/EaI, occurred in elderly hypertensive women and was coincident
      with the alteration of cardiac dimensions. The coincidence with the changes in
      diastolic function and the alterations of cardiac dimensions occurred in a
      different time point between the sexes.

PMID- 27867529
TI  - Coexistence of apical hypertrophic cardiomyopathy and endomyocardial fibrosis
      with calcification: diagnosis using multimodality imaging.
AB  - A 48-year-old man from West Africa was evaluated for dyspnea. Echocardiography
      showed an echolucent mass at the left ventricular apex surrounded by a dense
      ridge of tissue, suggesting endomyocardial fibrosis (EMF). Doppler
      echocardiography showed restrictive hemodynamics and intramyocardial coronary
      blood flow at the hypertrophied apex, suggesting apical hypertrophic
      cardiomyopathy (ApHCM) with calcified thrombus. Cardiac magnetic resonance
      imaging showed a thickened myocardium with apical cavity obliteration and
      endomyocardial calcification, and gadolinium contrast demonstrated marked bright
      subendocardial and diffuse patchy intramyocardial hyperenhancement in the
      hypertrophied apical wall segment, confirming coexistence of EMF and ApHCM.
      Workup for known disorders of calcification was negative.

PMID- 27867527
TI  - The CHA2DS2-VASc score as a predictor of high mortality in hospitalized heart
      failure patients.
AB  - AIMS: Atrial fibrillation (AF) is common in patients with heart failure (HF).
      CHA2DS2-VASc score was originally employed as a risk assessment tool for stroke
      in patients with AF; however, it has recently been used to predict not only
      stroke but also various cardiovascular diseases beyond the original AF field. We
      aimed to verify the CHA2DS2-VASc score as a risk assessment tool to predict
      mortality in patients with HF. METHODS AND RESULTS: Consecutive 1011 patients
      admitted for treatment of HF were divided into three groups based on their
      CHA2DS2-VASc scores: score 1-3 group (n = 317), score 4-6 group (n = 549) and
      score 7-9 group (n = 145). Of the 1011 HF patients, 387 (38.3%) had AF. We
      compared patient characteristics among the three groups and prospectively
      followed for all-cause mortality. Although left ventricular ejection fraction was
      similar among all three groups, all-cause mortality was higher in the score 4-6
      group and score 7-9 group than in the score 1-3 group (37.9 and 29.3% vs. 15.1%,
      log-rank P < 0.001). In the multivariable Cox proportional hazard analysis, the
      CHA2DS2-VASc score 7-9 was an independent predictor of all-cause mortality (all
      HF patients: hazard ratio (HR) 1.822, P = 0.011; HF patients with AF: HR 1.951, P
      = 0.031; HF patients without AF: HR 2.215, P = 0.033). CONCLUSIONS: The CHA2DS2
      VASc score was an independent predictor of all-cause mortality in HF patients
      with or without AF. This comprehensive risk assessment score may help identify HF
      patients who are at high risk for mortality in HF patient.

PMID- 27867530
TI  - Continuous renal replacement therapy for haemodynamic collapse and rhabdomyolysis
      induced by pheochromocytoma crisis.
AB  - Pheochromocytoma associated with pregnancy is not common. Caesarean section may
      induce pheochromocytoma crisis, resulting in a lethal condition. The clinical
      picture of pheochromocytoma crisis is extremely variable. In this report, we
      describe a case of severe pheochromocytoma crisis induced by caesarean section
      presenting with hyperpyrexia, haemodynamic collapse, muscle weakness, heart
      failure, and acute kidney injury. Furthermore, we report that the muscle weakness
      was a manifestation of rhabdomyolysis, resulting from the pheochromocytoma
      crisis. Standard medical therapy failed to halt the patient's rapidly
      deteriorating condition. Continuous renal replacement therapy removed
      catecholamines from the circulation, resulting in improvement of haemodynamics
      and abrogation of rhabdomyolysis.

PMID- 27867531
TI  - Steroid pulse therapy was effective for cardiac sarcoidosis with ventricular
      tachycardia and systolic dysfunction.
AB  - A 32-year-old man presented with palpitation. He was diagnosed with pulmonary
      sarcoidosis by lung biopsy. The electrocardiogram showed first-degree
      atrioventricular block and complete right bundle branch block (CRBBB). We planned
      to examine laboratory data, echocardiography, Holter monitoring, and gallium-67
      scintigraphy. Before he went through all these exams, he developed ventricular
      tachycardia. After defibrillation was performed, his electrocardiogram revealed
      complete atrioventricular block. We observed elevation of serum angiotensin
      converting enzyme levels. In addition, both of gallium-67 scintigraphy and 18F
      fluorodeoxyglucose positron emission tomography showed abnormal uptake in the
      ventricular septum. We diagnosed the patient with cardiac sarcoidosis associated
      with these arrhythmias. We started treatment with methylprednisolone pulse
      therapy (1 g daily). After 3 days of steroid pulse therapy, we administered
      prednisolone 30 mg daily. On day 15, electrocardiogram changed from complete
      atrioventricular block to first-degree atrioventricular block and CRBBB. He was
      discharged with no progression with cardiac sarcoidosis for 2 years.

PMID- 27867532
TI  - Left ventricular ejection fraction recovery in patients with heart failure
      treated with intravenous iron: a pilot study.
AB  - AIMS: In patients with heart failure with reduced ejection fraction (HFrEF) and
      iron deficiency, treatment with intravenous iron has shown a clinical improvement
      regardless of anaemic status. Cardiac magnetic resonance (CMR) T2* sequence has
      shown a potential utility for evaluating myocardial iron deficiency. We aimed to
      evaluate whether T2* sequence significantly changes after ferric carboximaltose
      (FCM) administration, and if such changes correlate with changes in left
      ventricle ejection fraction (LVEF). METHODS AND RESULTS: In this pilot study, we
      included eight patients with chronic symptomatic (New York Heart Association II
      III) HFrEF and iron deficiency. A CMR, including T2* analysis, was performed
      before and at a median of 43 days (interquartile range = 35-48) after intravenous
      FCM administration. Pearson or Spearman correlation coefficient (r) was used for
      bivariate contrast as appropriate. A partial correlation analysis was performed
      between DeltaLVEF and DeltaT2* while controlling for anaemia status at baseline.
      Anaemia was present in half of patients. After FCM administration, T2* decreased
      from a median of 39.5 (35.9-48) to 32 ms (32-34.5), P = 0.012. Simultaneously, a
      borderline increase in median of LVEF [40% (36-44.5) to 48.5% (38.5-53), P =
      0.091] was registered. In a bivariate correlational analysis, DeltaT2* was highly
      correlated with DeltaLVEF (r = -0.747, P = 0.033). After controlling for anaemia
      at baseline, the association between DeltaT2* and DeltaLVEF persisted
      [r(partial): -0.865, R2(partial): 0.748, P = 0.012]. A median regression analysis
      backed-up these findings. CONCLUSIONS: In a small sample of patients with HFrEF
      and iron deficiency, myocardial iron repletion assessed by CMR was associated to
      left ventricular remodelling. Further studies are warranted.

PMID- 27867533
TI  - The HECT domain ubiquitin ligase HUWE1 targets unassembled soluble proteins for
      degradation.
AB  - In eukaryotes, many proteins function in multi-subunit complexes that require
      proper assembly. To maintain complex stoichiometry, cells use the endoplasmic
      reticulum-associated degradation system to degrade unassembled membrane subunits,
      but how unassembled soluble proteins are eliminated is undefined. Here we show
      that degradation of unassembled soluble proteins (referred to as unassembled
      soluble protein degradation, USPD) requires the ubiquitin selective chaperone
      p97, its co-factor nuclear protein localization protein 4 (Npl4), and the
      proteasome. At the ubiquitin ligase level, the previously identified protein
      quality control ligase UBR1 (ubiquitin protein ligase E3 component n-recognin 1)
      and the related enzymes only process a subset of unassembled soluble proteins. We
      identify the homologous to the E6-AP carboxyl terminus (homologous to the E6-AP
      carboxyl terminus) domain-containing protein HUWE1 as a ubiquitin ligase for
      substrates bearing unshielded, hydrophobic segments. We used a stable isotope
      labeling with amino acids-based proteomic approach to identify endogenous HUWE1
      substrates. Interestingly, many HUWE1 substrates form multi-protein complexes
      that function in the nucleus although HUWE1 itself is cytoplasmically localized.
      Inhibition of nuclear entry enhances HUWE1-mediated ubiquitination and
      degradation, suggesting that USPD occurs primarily in the cytoplasm. Altogether,
      these findings establish a new branch of the cytosolic protein quality control
      network, which removes surplus polypeptides to control protein homeostasis and
      nuclear complex assembly.

PMID- 27867535
TI  - Erratum: Canonical Wnt signalling regulates nuclear export of Setdb1 during
      skeletal muscle terminal differentiation.
AB  - [This corrects the article DOI: 10.1038/celldisc.2016.37.].

PMID- 27867534
TI  - NANOG reprograms prostate cancer cells to castration resistance via dynamically
      repressing and engaging the AR/FOXA1 signaling axis.
AB  - The pluripotency transcription factor NANOG has been implicated in tumor
      development, and NANOG-expressing cancer cells manifest stem cell properties that
      sustain tumor homeostasis, mediate therapy resistance and fuel tumor progression.
      However, how NANOG converges on somatic circuitry to trigger oncogenic
      reprogramming remains obscure. We previously reported that inducible NANOG
      expression propels the emergence of aggressive castration-resistant prostate
      cancer phenotypes. Here we first show that endogenous NANOG is required for the
      growth of castration-resistant prostate cancer xenografts. Genome-wide chromatin
      immunoprecipitation sequencing coupled with biochemical assays unexpectedly
      reveals that NANOG co-occupies a distinctive proportion of androgen
      receptor/Forkhead box A1 genomic loci and physically interacts with androgen
      receptor and Forkhead box A1. Integrative analysis of chromatin
      immunoprecipitation sequencing and time-resolved RNA sequencing demonstrates that
      NANOG dynamically alters androgen receptor/Forkhead box A1 signaling leading to
      both repression of androgen receptor-regulated pro-differentiation genes and
      induction of genes associated with cell cycle, stem cells, cell motility and
      castration resistance. Our studies reveal global molecular mechanisms whereby
      NANOG reprograms prostate cancer cells to a clinically relevant castration
      resistant stem cell-like state driven by distinct NANOG-regulated gene clusters
      that correlate with patient survival. Thus, reprogramming factors such as NANOG
      may converge on and alter lineage-specific master transcription factors broadly
      in somatic cancers, thereby facilitating malignant disease progression and
      providing a novel route for therapeutic resistance.

PMID- 27867536
TI  - Life-threatening MRSA sepsis with bilateral pneumonia, osteomyelitis, and septic
      arthritis of the knee in a previously healthy 13-year-old boy: a case report.
AB  - The incidence and severity of methicillin resistant Staphylococcus aureus (MRSA)
      infections are increasing and cause high mortality and morbidity. We describe the
      first pediatric case in Scandinavia with Panton-Valentine leucocidin (PVL)
      positive MRSA septicemia who developed bilateral pneumonia, arthritis of the
      knee, and osteomyelitis of the tibia. Radiological investigation and
      interpretation directed the treatment, especially the surgical debridement, and
      combined with clinical and biochemical findings lead to close interdisciplinary
      treatment with frequent surgical interventions and antimicrobial combination
      therapy. The outcome was a healthy patient without sequelae, a favorable course
      unlike those previously described in the literature. This case underlines the
      necessity of a close interdisciplinary cooperation in children with severe MRSA
      infection encompassing pneumonia, septic arthritis, and osteomyelitis, using
      different imaging modalities to guide the surgical and antibiotic treatment.

PMID- 27867537
TI  - Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatin via
      autophagy.
AB  - Cisplatin (cDDP) remains one of the first-line chemotherapeutic agents for
      gastric cancer (GC) treatment, and resistance to cDDP is the major limitation in
      its clinical application. Mechanisms of cDDP resistance have been shown to be
      varied and complicated. Aquaporin 3 (AQP3) has been demonstrated to be
      overexpressed in GC tissues and is thought to be involved in GC carcinogenesis
      and progression. However, the role of AQP3 in chemosensitivity of GC to cytotoxic
      agents remains unknown. In this study, we show that AQP3 overexpression induced
      resistance to cDDP in AGS cells (P<0.05), and AQP3 knockdown increased the
      chemosensitivity in MGC803 and SGC7901 cells (P<0.05). Moreover, cDDP treatment
      enhanced AQP3 expression in MGC803, SGC7901 and AGS cells. AQP3 overexpression
      promoted the conversion of LC3-I to LC3-II in AGS cells, whereas AQP3 knockdown
      inhibited this conversion in MGC803 and SGC7901 cells. AQP3 upregulation
      increased Atg5 and Beclin-1 expression, and inhibited P62 expression in AGS
      cells, whereas AQP3 knockdown showed the opposite results in MGC803 and SGC7901
      cells. Chloroquine (CQ), an autophagy inhibitor, enhanced the cytotoxicity of
      cDDP in GC cells, and CQ reversed the chemoresistance to cDDP caused by AQP3
      overexpression in GC cells. Together, our data demonstrate that AQP3 facilitates
      cisplatin resistance in gastric cancer cells via autophagy, and suggest that the
      development of AQP3-based tumor therapeutics could play a key role in future GC
      treatment strategies.

PMID- 27867539
TI  - Statistical modeling to unravel multiple predictors of the choice of chemotherapy
      for non-small cell lung cancer.

PMID- 27867540
TI  - Circulating biomarker for malignant pleural mesothelioma diagnosis: pay attention
      to study design.

PMID- 27867538
TI  - Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB):
      evidence and perspectives.

PMID- 27867541
TI  - Percutaneous coronary intervention versus bypass grafting in left main coronary
      artery disease.

PMID- 27867542
TI  - The expression of SALL4 is significantly associated with EGFR, but not KRAS or
      EML4-ALK mutations in lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide;
      unfortunately, its prognosis is still very poor. Therefore, developing the target
      molecular is very important for lung cancer diagnosis and treatment, especially
      in the early stage. With this in view, spalt-like transcription factor 4 (SALL4)
      is considered a potential biomarker for diagnosis and prognosis in cancers,
      including lung cancer. METHODS: In order to better investigate the association
      between the expression of SALL4 and driver genes mutation, 450
      histopathologically diagnosed patients with lung cancer and 11 non-cancer
      patients were enrolled to test the expression of SALL4 and the status of driver
      genes mutation. This investigation included epidermal growth factor receptor
      (EGFR), kirsten rat sarcoma viral oncogene homolog (KRAS), and a fusion gene of
      the echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic
      lymphoma kinase (ALK). RESULTS: The results of the study showed that females
      harbored more EGFR mutation in adenocarcinoma (ADC). The mutation rate of KRAS
      and EML4-ALK was about 5%, and the double mutations of EGFR/EML4-ALK were higher
      than EGFR/KRAS. In the expression analysis, the expression of SALL4 was much
      higher in cancer tissues than normally expected, especially in tissues that
      carried EGFR mutation (P<0.05), however, there were no significant differences
      between different mutation types. Likewise, there were no significant differences
      between expression of SALL4 and KRAS and EML4-ALK mutations. CONCLUSIONS: SALL4
      is up regulated in lung cancer specimens and harbors EGFR mutation; this finding
      indicates that SALL4 expression may be relevant with EGFR, which could provide a
      new insight to lung cancer therapy. The mechanism needs further investigation and
      analysis.

PMID- 27867543
TI  - Primary adenosquamous carcinoma of the esophagus: an analysis of 39 cases.
AB  - BACKGROUND: Adenosquamous carcinoma (ASC) of the esophagus is an uncommon type of
      malignant esophageal neoplasm containing both squamous cell carcinoma (SCC) and
      adenocacinoma (AC) components. The aim of this study was to explore the clinical
      characteristics and prognosis of esophageal ASC. METHODS: A retrospective review
      of esophageal ASC patients who underwent transthoracic esophagectomy with
      lymphadenectomy in our hospital from July 2007 to April 2014. RESULTS: A total of
      39 (1.0%) esophageal ASC patients among 3855 patients with esophageal cancers
      were collected to analyze. There were 34 men and 5 women with a median age of
      61.0 years (range from 39-85). Median follow-up time was 30.0 months and median
      survival time was 44.4 months. The 1-, 3- and 5-year overall survival rates were
      82.1%, 51.6% and 37.5%, respectively. Compared to esophageal SCC and AC, there
      were no significant difference in survive time (P=0.616). Thirty five (92.1%) of
      the 38 patients who underwent preoperative endoscopic biopsy were misdiagnosed,
      mostly as SCC. Fifteen patients (38.5%) were found to have lymph node metastasis.
      Thirty two patients (82.1%) had a poorly differentiated or undifferentiated
      tumor. According to the 2009 American Joint Committee on Cancer (AJCC) staging
      system for esophageal squamous cell carcinoma, 3 patients were at Stage I, 21
      patients at Stage II and 15 patients at Stage III. In univariate analysis, pT
      stage, lymph node metastasis and pTNM Stage significantly influenced survive
      time. In multivariate analysis, however, only lymph node metastasis (P=0.003; 95%
      CI: 1.626-10.972) was found to be the independent prognostic factor. CONCLUSIONS:
      Primary ASC of the esophagus is a rare disease with difficultly to be
      histologically confirmed by endoscopic biopsy. The prognosis of esophageal ASC
      was no worse than esophageal SCC and AC. Lymph node metastasis is the most
      influent prognostic factor. The TNM staging system of esophageal SCC is
      applicable for esophageal ASC.

PMID- 27867544
TI  - A morphologic study of the airway structure abnormalities in patients with asthma
      by high-resolution computed tomography.
AB  - BACKGROUND: Airway structure changes, termed as airway remodeling, are common in
      asthma patients due to chronic inflammation, which can be assessed by high
      resolution computed tomography (HRCT). Considering the controversial conclusions
      in the correlation of morphologic abnormalities with clinical feature and
      outcome, we aimed to further specify and evaluate the structural abnormalities of
      Chinese asthmatics by HRCT. METHODS: From August 2012 to February 2015,
      outpatients with asthma were recruited consecutively in the Asthma Center of West
      China Hospital, Sichuan University. Standard HRCT and pulmonary function test
      (PFT) were performed to collect information of bronchial wall thickening,
      bronchial dilatation, mucus impaction, emphysema, mosaic perfusion, atelectasis,
      and spirometric parameters. We reported the incidence of each structural
      abnormality in HRCT and compared it among different asthmatic severities.
      RESULTS: A total of 123 asthmatics were enrolled, among which 84 (68.3%) were
      female and 39 (31.7%) were male. At least one structural abnormality was detected
      by HRCT in 85.4% asthmatics, and the incidence of bronchial wall thickening,
      bronchial dilatation, mucus impaction, emphysema, mosaic perfusion, and
      atelectasis was 57.7%, 51.2%, 22%, 24.4%, 5.7% and 1.6%, respectively. The
      incidences of bronchial wall thickening, bronchial dilation and emphysema were
      significantly increased by asthma severity (P<0.05), while incidences of mucus
      impaction (26/27, 96.30%), mosaic perfusion (6/7, 85.71%) and atelectasis (2/2,
      100%) were mainly found in severe asthma. We found a longer asthma history
      (28.13+/-18.55 years, P<0.001, P=0.003), older age (51.30+/-10.70 years, P=0.022,
      P=0.006) and lower predicted percentage of forced expiratory volume in one second
      (FEV1%) (41.97+/-15.19, P<0.001, P<0.001) and ratio of forced expiratory volume
      to forced vital capacity (FEV1/FVC) (48.01+/-9.55, P<0.001, P<0.001) in patients
      with severe bronchial dilation compared with those in none and mild bronchial
      dilation. A negative correlation was also found between the extent of bronchial
      dilation and FEV1% as well as FEV1/FVC (r=-0.359, P=0.004; r=-0.266, P=0.035,
      respectively). CONCLUSIONS: The incidences of structural abnormalities detected
      by HRCT are fairly high in Chinese asthma populations, especially the bronchial
      wall thickening and bronchial dilation, which are significantly increased in
      severe asthma, and are potential risk factors of pulmonary function decline in
      asthmatics.

PMID- 27867545
TI  - An evaluation study of research efficiency of the Guangzhou institute of
      respiratory diseases based on malmquist index.
AB  - BACKGROUND: This study aimed to analyze the dynamic changes of the scientific
      research innovation efficiency of Guangzhou Institute of Respiratory Diseases
      (GIRD) during the year 2009-2013 to explore the reason for these changes and give
      some suggestions on how to improve the overall efficiency of the Institute.
      METHODS: The panel data used in this study were taken from 19 research teams of
      GIRD during 2009 to 2013. Data envelopment analysis (DEA) based on Malmquist
      index (MI) was used to analyze the performance of each research team in terms of
      productivity changes over time. Data were analyzed using DEAP 2.1 software.
      RESULTS: The annual average increase rate of total factor productivity (TFP),
      technological progress, technical efficiency, pure technical efficiency, and
      scale efficiency was 30.4%, 22.5%, 6.4%, 0.9%, and 5.4%, respectively from 2009
      to 2013. The scientific research innovation efficiency of the GIRD was generally
      high and kept on growing. The increase of TFP was mainly caused by the progress
      of tech, the descending of TFP in some teams should be mainly attributable to the
      declining pure technical efficiency, and scale efficiency on the whole,
      maintaining a stable growth at a low speed. CONCLUSIONS: To achieve higher
      scientific research innovation, GIRD not only needs to further improve the
      management level and introduce advanced management mode, but also needs to focus
      on optimization of resource allocation, as well as to strengthen the talent
      introduction, and continue to maintain the absorption of new technologies and
      innovation.

PMID- 27867546
TI  - Transoral endoscopic mediastinal surgery (TOEMS)-results of a first clinical
      study for scarless mediastinal lymph node biopsies.
AB  - BACKGROUND: Video-assisted mediastinoscopy (VAM) represents the standard
      procedure for mediastinal lymph node biopsies. This operation results in a scar
      at prominent position at the anterior neck. Since there is a trend to less
      invasive procedures, natural orifice transluminal endoscopic surgery (NOTES) was
      introduced to different fields of surgery. Based on NOTES we developed a new
      approach for mediastinoscopy: transoral endoscopic mediastinal surgery (TOEMS).
      In previous studies using human cadavers and living pigs the feasibility of TOEMS
      was shown. It was unclear whether TOEMS could be safely applied in patients
      requiring mediastinal lymph node biopsies. METHODS: We conducted a clinical phase
      I study recruiting ten patients with unclear mediastinal lymphadenopathy not
      resolved by prior bronchoscopy. All patients underwent TOEMS for mediastinal
      lymph node biopsy. The duration of the procedure and complications were
      monitored. In addition, all patients were examined for pain, swallowing
      dysfunction and sensation disturbance. RESULTS: TOEMS was accomplished in eight
      patients. In two patients operation was converted to VAM due to technical
      problems. Mediastinal lymph nodes were dissected in all patients who finished
      with TOEMS. On average, two separate lymph stations were reached by TOEMS.
      Duration of the procedure was 159+/-22 min. Permanent palsy of the right
      recurrent laryngeal nerve was noticed in one patient postoperatively.
      CONCLUSIONS: This is the first report for a human application of NOTES in
      thoracic surgery. In fact, transoral endoscopic surgery seems to be a feasible
      approach for mediastinal lymph node biopsies. Further studies are needed to show
      whether this procedure has an advantage over VAM in terms of pain, complications
      and accessibility of mediastinal lymph node stations.

PMID- 27867547
TI  - Clinicopathological features and prognosis of patients <45 years old with
      esophageal adenocarcinoma comparing to other age groups.
AB  - BACKGROUND: To analyze the clinicopathological features and prognosis of younger
      patients with esophageal adenocarcinoma (EAC). METHODS: A total of 2,601 patients
      diagnosed with EAC between 1988 and 2011 were selected from the Surveillance,
      Epidemiology, and End Results (SEER) database. All patients underwent primary
      tumor resection and regional lymphadenectomy without preoperative radiotherapy.
      The patients were into four age groups (<45, 45-59, 60-74, >=75), with 94, 813,
      1,272 and 422 patients in each group respectively. RESULTS: Patients in the age
      <45 group were more likely to have lymph node (LN) metastasis (P=0.002),
      postoperative radiotherapy (P<0.001) and advanced T and N stage (P=0.003, 0.014)
      compared to the other three groups. We then conducted two Cox proportional
      hazards model adjusted for the sex, race, number of LNs examined, histological
      grade, postoperative radiation. The hazard ratio (HR) was higher in patients <45
      y and the survival rate were paradoxically lower compared to the patients between
      45-60 years old (P=0.046, 0.039). CONCLUSIONS: The patients <45 y had the most
      aggressive clinicopathological features of EAC and poorer survival rate after
      radical esophagectomy.

PMID- 27867548
TI  - Detection of salivary aspiration using radionuclide salivagram SPECT/CT in
      patients with COPD exacerbation: a preliminary study.
AB  - BACKGROUND: The aim of this prospective study was to assess the utility of
      radionuclide salivagram for detecting salivary aspiration in AECOPD patients and
      to evaluate the adding value of SPECT/CT to planar imaging. METHODS: 52
      consecutive AECOPD patients underwent radionuclide salivagram SPECT/CT and water
      swallow test between April 2012 and March 2014. All images were interpreted
      independently by two experienced nuclear medicine physicians. Final diagnosis was
      made by consensus of two readers. The radionuclide salivagram and water swallow
      test results were compared using kappa values. The relationship between
      radionuclide salivagram results and exacerbation frequency was evaluated with the
      Person chi2 test. RESULTS: Salivary aspiration was diagnosed by radionuclide
      salivagram in 17 of 52 patients. Aspiration into the right main bronchus and
      branch was seen in 8 patients, bilateral main bronchi in 6 patients, and left
      lung field in 3 patients. SPECT/CT provided more accurate information on the
      extent and location of salivary aspiration, in 11 cases, SPECT/CT demonstrated
      aspiration of pulmonary segment bronchus and the following areas. Moreover,
      SPECT/CT revealed salivary aspiration corresponding to aspiration pneumonia in 8
      cases. There was general agreement between the radionuclide salivagram and water
      swallow test results (Kappa =0.712; 95% CI, 0.504-0.920; P<0.001). The incidence
      of frequent exacerbations was greater among subjects with positive salivagram
      than among those with negative salivagram results (RR =3.43; 95% CI, 1.90-6.19;
      P<0.001). CONCLUSIONS: Radionuclide salivagram is an objective method for
      detecting salivary aspiration in AECOPD patients. Moreover, SPECT/CT can identify
      more precise location of salivary aspiration and suggest a possible role for
      saliva in the pathophysiology of aspiration pneumonia.

PMID- 27867549
TI  - Continuous positive airway pressure therapy in non-sleepy patients with
      obstructive sleep apnea: results of a meta-analysis.
AB  - BACKGROUND: Although continuous positive airway pressure (CPAP) has become the
      first line of therapy for obstructive sleep apnea (OSA), it remains controversial
      whether non-sleepy patients could benefit from CPAP treatment. METHODS: We
      searched the online databases Medline, Embase, the Cochrane library and the
      Cochrane Central Registry of Controlled Trials to select eligible control trials,
      including non-sleepy OSA patients and those patients treated by CPAP or either
      sham CPAP or no CPAP. RESULTS: Seven eligible studies (1,541 patients) were
      included. The pooled estimates of the mean changes after CPAP treatment for the
      systolic blood pressure (SBP) and diastolic blood pressure (DBP) were -0.51 mmHg
      (95% CI, -3.39 to 2.38 mmHg; P=0.73) and -0.92 mmHg (95% CI, -1.39 to -0.46 mmHg;
      P<0.001), respectively. CPAP should not improve subjective sleepiness in the
      minimally symptomatic OSA patients, as the change in the Epworth sleepiness scale
      (ESS) was -0.51 (95% CI, -1.68 to 0.67; P=0.397). However, CPAP can effectively
      reduce AHI or ODI by 15.57 events/h (95% CI, -29.32 to -1.82; P=0.026) compared
      to controls. However, the risk of cardiovascular events did not significantly
      decrease [odds ratio (OR), 0.80; 95% CI, 0.50 to 1.26; P=0.332] in the end.
      CONCLUSIONS: CPAP treatment can reduce OSA severity in non-sleepy patients and
      minutely reduce the DBP, but CPAP seems to have no overall beneficial effects on
      subjective sleepiness, SBP, or cardiovascular risk.

PMID- 27867550
TI  - Amide-linked local anesthetics induce apoptosis in human non-small cell lung
      cancer.
AB  - BACKGROUND: A retrospective analysis of patients undergoing cancer surgery
      suggested that using local anesthetics could reduce cancer recurrence and improve
      survival rate. Previous studies have indicated that local anesthetics may induce
      apoptosis in several kinds of cells in vitro, but the mechanism is unclear.
      METHODS: Cell viability was analyzed by MTS; reactive oxygen species (ROS),
      mitochondrial membrane potential (MMP, ?Psim), cell cycle distribution, and cell
      apoptosis assay were detected by flow cytometry; DNA damage was measured by comet
      assay; cell invasion and migration were observed by microscopy; The expression
      level of related proteins was detected by western blot assay. RESULTS: The
      results indicated that lidocaine and ropivacaine could decrease viability, induce
      G0/G1 phase arrest and apoptosis in human non-small cell lung cancer (NSCLC)
      cells A549 and H520. Invasion and migration were suppressed. Western blot
      indicated the related apoptotic pathways proteins changed accordingly.
      Additionally, lidocaine and ropivacaine downregulated ?Psim, provoked DNA damage,
      upregulated ROS production and activated mitogen-activated protein kinase (MAPK)
      pathways in A549 and H520 cells. CONCLUSIONS: The cytotoxic effect of amide
      linked local anesthetics on NSCLC cells were mainly due to apoptosis. The
      antitumor mechanism of lidocaine and ropivacaine may involve apoptotic pathways
      and MAPK pathways.

PMID- 27867551
TI  - Endobronchial ultrasonography with guide sheath versus computed tomography guided
      transthoracic needle biopsy for peripheral pulmonary lesions: a propensity score
      matched analysis.
AB  - BACKGROUND: Computed tomography guided transthoracic needle aspiration (CT-TTNA)
      and endobronchial ultrasonography with guide sheath (EBUS-GS) transbronchial lung
      biopsy are important methods for the diagnosis of peripheral pulmonary lesions
      (PPLs). Without enough evidence, it is controversial which is a better choice for
      diagnosing PPLs. In this study, we hypothesized that the complication rate of
      EBUS-GS would be lower than CT-TTNA and the diagnostic accuracy of EBUS-GS were
      not inferior to CT-TTNA. METHODS: This study was a retrospective analysis of a
      prospective registry with propensity matching. Patients with PPLs were divided
      into EBUS-GS group and CT-TTNA group according to patients' intent to treatment.
      Pathological results and procedure related complications of EBUS-GS and CT-TTNA
      were recorded. Propensity score matching(PSM) was used to eliminate the
      intergroup bias. Diagnostic yields and complications of two groups were compared.
      Subgroup analysis was performed to conclude the indications of different
      procedures. RESULTS: A total of 187 patients (CT-TTNA: 130; EBUS-GS: 57) were
      enrolled. After propensity score matching, 54 paired patients were included.
      Diagnostic yield was 81% (44/54) for EBUS-GS and 87% (47/54) for CT-TTNA
      (P=0.43), respectively. Diagnostic sensitivity in malignancy was 93% (42/45) for
      CT-TTNA and 79% (37/47) for EUBS-GS (P=0.04). Subgroup analysis revealed that the
      sensitivity of CT-TTNA was significantly higher in diagnosing of lesions close to
      the chest wall (100% vs. 80%, P=0.04), and bronchus sign on CT was a predictive
      factor for accurate diagnosis by EBUS-GS. The overall complication rate was 13%
      (7/54) for CT-TTNA group, which was not significantly higher than that of EBUS-GS
      group (2%, P=0.06). Subgroup analysis showed that patients combined with
      pulmonary comorbidities and lesions apart from chest wall were risk factors for
      complications of CT-TTNA. CONCLUSIONS: Both of the two procedures are effective
      for the diagnosis of PPLs, but CT-TTNA has a higher diagnostic sensitivity for
      malignancy. EBUS-GS has fewer complications, and it is more suitable for patients
      combined with pulmonary comorbidities and lesions with bronchus signs.

PMID- 27867552
TI  - Prognostic value of on admission arterial PCO2 in hospitalized patients with
      community-acquired pneumonia.
AB  - BACKGROUND: There is little data about the correlation between the outcome of
      community acquired pneumonia (CAP) and the hypercapnic type respiratory failure.
      In this study we prospectively investigated the prognostic significance of first
      arterial CO2 tension in patients hospitalized with CAP. METHODS: In this
      prospective study patients with CAP, admitted to a general hospital were
      included. PaCO2 was measured for each subject in an arterial blood sample drawn
      in the first 2 hours and its correlations with three major outcomes were
      evaluated: intensive care unit (ICU) admission, duration of admission and
      mortality in 30 days. RESULTS: A total of 114 patients (mean age: 60.9+/-18.3;
      male: 51.8%) diagnosed with CAP were included. Significant relationship was not
      found between PaCO2 and mortality (P=0.544) or ICU admission (P=0.863). However
      advanced age, associated CHF, high BUN levels, high CURB-65 scores, associated
      pleural effusion in chest X-ray and being admitted to the ICU (P=0.012, 0.004,
      0.003, <0.001, 0.045 and <0.001 respectively) were all significant prognostic
      factors of higher mortality risks. Prognostic factors for ICU admission were a
      history of malignancy (P=0.004), higher CURB-65 (P<0.001) scores and concomitant
      pleural effusion (P=0.028) in chest X-ray. Hypercapnic patients hospitalized for
      longer duration compared with normocapnic subjects. Furthermore, patients with
      lower pH (P=0.041) and pleural effusions (P=0.002) were hospitalized longer than
      the others. CONCLUSIONS: There was less prominent prognostic value regarding on
      admission PaCO2 in comparison to other factors such as CURB-65. Considering the
      inconsistent results of surveys conducted on prognostic value of PaCO2 for CAP
      outcomes, further investigations are required to reach a consensus on this
      matter.

PMID- 27867553
TI  - Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung
      cancer patients from subjects with no lung cancer.
AB  - BACKGROUND: Breath alkanes are reported to be able to discriminate lung cancer
      patients from healthy people. A simple chemiresistor-based sensor was designed to
      respond to alkanes by a change in resistance measured by a digital multimeter
      connected to the sensor. In preclinical experiments, the sensor response was
      found to have a strong positive linear relationship with alkane compounds and not
      responsive to water. This study aimed to determine the ability of the alkane
      sensor to distinguish the exhaled breaths of lung cancer patients from that of
      chronic obstructive pulmonary disease (COPD) patients and control subjects
      without lung cancer. METHODS: In this cross-sectional study, 12 treatment-naive
      patients with lung cancer, 12 ex- or current smokers with COPD and 13 never
      smokers without lung disease were asked to exhale through a drinking straw into a
      prototype breath-in apparatus made from an empty 125 mL Vitagen(r) bottle with
      the chemiresistor sensor attached at its inside bottom to measure the sensor peak
      output (percentage change of baseline resistance measured before exhalation to
      peak resistance) and the time taken for the baseline resistance to reach peak
      resistance. RESULTS: Analysis of multivariate variance and post-hoc Tukey test
      revealed that the peak output and the time to peak values for the lung cancer
      patients were statistically different from that for both the COPD patients and
      the controls without lung disease, Pillai's Trace =0.393, F=3.909, df = (4, 64),
      P=0.007. A 2.20% sensor peak output and a 90-s time to peak gave 83.3%
      sensitivity and 88% specificity in diagnosing lung cancer. Tobacco smoking did
      not affect the diagnostic accuracy of the sensor. CONCLUSIONS: The alkane sensor
      could discriminate patients with lung cancer from COPD patients and people
      without lung disease. Its potential utility as a simple, cheap and non-invasive
      test for early lung cancer detection needs further studies.

PMID- 27867554
TI  - Tigecycline combination for ventilator-associated pneumonia caused by extensive
      drug-resistant Acinetobacter baumannii.
AB  - BACKGROUND: Extensive drug-resistant Acinetobacter baumannii (XDR A. baumannii)
      has emerged as an important pathogen in patients with ventilator-associated
      pneumonia (VAP) worldwide. This study determined whether or not combination
      tigecycline (TGC) treatment improved the short-term outcome of patients with XDR
      A. baumannii-induced VAP. Methods: Fifty-eight patients admitted to our intensive
      care unit (ICU) with confirmed XDR A. baumannii VAP between January 2011 and June
      2013 were retrospectively studied. Fourteen patients were excluded. The included
      subjects were classified into two groups depending on treatment regimens with or
      without TGC (TGC group, n=20; non-TGC group, n=24). Thirty-day mortality rates,
      and clinical and microbiologic responses were reviewed and compared in detail.
      RESULTS: Microbiological eradication was observed in 3 patients (15.0%) in the
      TGC group and 7 patients (29.2%) in the non-TGC group (P=0.264). The mean time-to
      eradication of XDR A. baumannii was 5.3+/-2.1 versus 7.6+/-4.0 days (P=0.395).
      Ten of 20 (50%) patients developed resistance to TGC after initiation of TGC
      therapy in the TGC group. Clinical cure were achieved in 50.0% of the patients
      (10/20) in the TGC group and 45.8% of the patients (7/24) in the non-TGC group
      (P=1.000). No differences existed in the 30-day mortality, length of ICU stay,
      length of hospital stay (LOS), and length of invasive mechanical ventilation (MV)
      between the two groups. The occurrence of septic shock was significantly lower in
      the TGC group (20.0% vs. 54.2%; P=0.030). CONCLUSIONS: TGC combination therapy
      did not improve the clinical cure and microbiologic eradication in patients with
      XDR A. baumannii VAP. TGC combination therapy did not decrease all-cause
      mortality in patients with XDR A. baumannii VAP. TGC combination therapy reduced
      the incidence of septic shock in patients with XDR A. baumannii VAP, and might
      decrease the incidence of poly-microbial VAP. TGC combination therapy can only be
      recommended as an option when other optimized therapeutics, such as colistin, are
      unavailable.

PMID- 27867555
TI  - Functional role of lncRNA DB327252 in lung cancer.
AB  - BACKGROUND: Lung cancer becomes a concerning health issue and is considered one
      of the most deadly cancers in the worldwide. Most recently, long non-coding RNAs
      (lncRNAs) are newfound non-coding RNAs that are thought as one of the major
      players in a range of biological processes of human diseases. Although lncRNAs
      are involved in numerous cancer types, the precise understandings of lncRNAs'
      functional roles and mechanisms in lung cancer are limited. In this study, we
      looked for lung cancer related lncRNAs. METHODS: The quantitative reverse
      transcriptase polymerase chain reaction (qRT-PCR) technique was utilized to
      investigate the lncRNA DB327252 expression in 91 paired clinical lung cancer
      tissues and related cell lines. Moreover, its biological functions were also
      evaluated in the development of lung cancer. RESULTS: The results indicated that
      the expression of DB327252 was up-regulated in lung cancer tissues compared to
      the cancer-adjacent normal tissues (P<0.05); and the up-regulated expression is
      likely to relate to those with bigger tumor size, adenocarcinoma and advanced TNM
      stage (P<0.05). In addition, the knockdown of DB327252 inhibited the growth and
      proliferation of tumor cell in vitro and in vivo. According to the observation
      from our study, we found that the knockdown of the DB327252 expression, led to
      G0/G1 phase cell-cycle arrested, colony formation suppressed in vitro, and tumor
      growth inhibited in a nude mouse xenograft model. Our experimental results also
      suggest that lncRNA DB327252 may be a lncRNA related to lung cancer and acts an
      important role in A549 and 16HBE-T cancer cells, which provides evidence that
      DB327252 has an oncogene-like function in lung cancer. CONCLUSIONS: The lncRNA
      DB327252 is up-regulated in lung cancer, and its expression implies that it was
      probable related to biologic functions of lung cancer.

PMID- 27867556
TI  - Recurrent laryngeal nerve lymph node dissection may not be suitable for all early
      stage esophageal squamous cell carcinoma patients: an 8-year experience.
AB  - BACKGROUND: Recurrent laryngeal nerve (RLN) injury is one of the most frequent
      postoperative complications of esophageal squamous cell carcinoma (ESCC) radical
      resection. This study aims to develop a novel scoring system to predict recurrent
      laryngeal nerve lymph node (RLNLN) metastases in early ESCC and explore the
      indications for precise RLN lymphadenectomy. METHODS: Early stage ESCC patients
      from 2006 to 2014 were analyzed. Patient and pathologic characteristics were
      compared between patients with RLNLN metastases and those without. Univariate and
      multivariate analyses were performed to establish a scoring system that estimates
      the risks of RLNLN metastases. The indications for RLNLN dissection were
      validated by survival rate, postoperative complications, and metastases rate.
      RESULTS: A total of 311 cases selected from 1,466 ESCC patients were divided into
      the dissection group and the control group. Age, tumor length, macroscopic tumor
      type, T stage, tumor location and tumor differentiation were independent
      predictors of RLNLN metastases. The weighted scoring system included age (+2 for
      <56 years), tumor length (+2 for over 4.45 cm), tumor location (+4 for upper
      thoracic, +2 for mid-thoracic) and macroscopic tumor type (+1 for advanced type).
      The total number of points estimated the probability of RLNLN metastases [low
      risk (0-2 point), 0%; moderate-risk (3-4 points), 9.8%; and high-risk (>4
      points), 43.4%]. Besides, the dissection group had more complications and similar
      survival rate when compared with the control group. CONCLUSIONS: We developed a
      novel scoring system that accurately estimated the risk of RLNLN metastases in
      early ESCC patients. RLN lymphadenectomy may be safely omitted for the patients
      in the low-risk subgroup.

PMID- 27867557
TI  - Clinical analysis of non-AIDS patients pathologically diagnosed with pulmonary
      cryptococcosis.
AB  - BACKGROUND: Pulmonary cryptococcosis (PC) was not a rare infectious disease in
      non-AIDS patients. However, data on the immune status were lacking in southern
      China for comparative analysis of differences between immunocompromised and
      immunocompetent hosts. This study was to investigate the epidemiological,
      clinical, radiological, and treatment profiles for patients with PC. METHODS: We
      performed a retrospective review of 88 patients diagnosed with tissue-confirmed
      PC who were not HIV-infected from 2003 to 2013. RESULTS: Of 88 patients,
      35(39.7%) were immunocompromised host. Fever and CNS symptom were significantly
      common in immunocompromised patients compared to immunocompetent patients
      (P=0.019 and P=0.036, respectively). The most frequent radiologic abnormalities
      were solitary or multiple pulmonary nodules, and masses or consolidations, and
      most lesions were located in the peripheral lung field. Cavitations and halo sign
      were significantly frequent in immunocompromised patients than in immunocompetent
      patients (P<0.05). The most frequently applied and reliable diagnostic procedure
      was CT-guided percutaneous translung biopsy. Treatment included antifungal drug
      alone in 20 patients, surgery alone in 20 including 3 treated by VATS, surgery
      plus antifungal drugs in 20 patients. CONCLUSIONS: PC was not rare in
      immunocompetent host in southern China. Special differences remained in clinical
      manifestation and radiological findings of PC between immunocompromised and
      immunocompetent patients. Future work on the mechanisms of possible differences
      is required.

PMID- 27867558
TI  - Effectiveness of lung ultrasonography for diagnosis of pneumonia in adults: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Pneumonia is usually presented as a forgotten killer, and an early
      diagnosis could largely improve the prognostic outcomes. Lung ultrasound (LUS)
      has been universally applied in evaluating multiple pulmonary diseases including
      pneumonia. However, the diagnosis accuracy of LUS for pneumonia in adults is
      still uncertain. Hence, we performed a systematic review of the current
      literature to assess the diagnosis accuracy of LUS for pneumonia in adults.
      METHODS: PubMed and EMBASE were searched for clinical trials that assessed the
      detection accuracy of LUS for pneumonia in adult patients. We extracted
      descriptive and quantitative information from eligible studies that met strict
      inclusion criteria and calculated pooled sensitivity, specificity and pooled
      diagnostic likelihood ratios (LR). Summary receiver operating characteristic
      (sROC) curve was used to assess the overall performance of LUS-based assays.
      RESULTS: We reviewed 1,072 articles and selected 38 for detailed review. 14
      articles containing 1,911 participants met all inclusion criteria and were
      included in the final analysis. LUS exhibited a pooled sensitivity of 0.904
      (0.884-0.921), specificity of 0.884 (0.861-0.904), positive LR of 6.6 (3.7-11.7),
      negative LR of 0.08 (0.04-0.19) and the area under curve (AUC) was 0.9611.
      Interestingly, when CT alone, CT combined with clinical presentations, and
      microbiology was set as the gold standard of pneumonia respectively, LUS
      demonstrated a pooled sensitivity of 90.9%, 95.0%, 53.3%, and a pooled
      specificity of 89.7%, 91.3% and 67.9%. In extension, we compared the diagnostic
      efficiency of LUS for pneumonia with chest X-ray (CXR) in 1,343 patients. The AUC
      for LUS and CXR was 0.972 and 0.867 respectively and the Z statistic of the two
      sROC curves was 2.31. CONCLUSIONS: Our study indicated that LUS is a robust
      diagnostic tool for pneumonia with high accuracy. Utilization of LUS would
      facilitate the estimation of pneumonia at bedside.

PMID- 27867559
TI  - Impact of anticancer drugs price cut on physician's prescription choices on first
      line chemotherapy regimens and health expenditure for advanced non-small cell
      lung cancer in China.
AB  - BACKGROUND: Increases in insurance coverage and price cut of drugs are two
      important measures to make health care more accessible and affordable. As far as
      we know, this was the first study to explore the impact of anticancer drug price
      cut on health expenses and oncologist's prescription decisions in China. METHODS:
      The 511 non-small cell lung cancer (NSCLC) patients were recruited from Qilu
      Affiliated Hospital of Shandong University from January 1, 2003 to December 31,
      2010. We categorized the patients into five groups based on China's fifth
      population census in 2000, including administrative group, workers and services
      group, peasants group, professionals group and others group. All statistical
      analyses were performed using SPSS (version 16.0), all statistic tests were two
      tailed and P value <=0.05 was considered significant. RESULTS: As for the first
      line chemotherapy regimens prescribed during the study, 27.6% patients received
      vinorelbine + cisplatin (NP), 31.5% and 30.9% patients had gemcitabine +
      cisplatin (GC) and docetaxel + cisplatin (DC), respectively, while only 4.3%
      patients received paclitaxel + cisplatin or carboplatin (TP). Before price policy
      implementation, NP was the most popularly used regimen (44.6%). By contrast,
      doctors' prescription choices changed significantly after drug price cut, GC took
      first place (42.0%). GC became the most expensive regimen (4,431.40 RMB per
      cycle, about 665.15 dollars per cycle), while NP cost the least (1,974.48 RMB per
      cycle, about 296.37 dollars per cycle) after price cut. No significant reduction
      could be seen for both the pharmaceutical spending and total expense per
      inpatient episode after drug price adjustment. One interesting phenomena was that
      doctors relied less on patient's sex, age, histology to make their decisions, by
      contrast, more on patient's occupation and health insurance type. And, the total
      drug cost was closely related to patient occupation and health insurance type.
      CONCLUSIONS: The introduction of anticancer drug price control policy was found
      to be ineffective on the containment of hospital drug expenditures in one cancer
      center in China.

PMID- 27867561
TI  - Comparison of robot-assisted esophagectomy and thoracoscopic esophagectomy in
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: The aim of the study was to compare robot-assisted esophagectomy (RE)
      with thoracoscopic esophagectomy (TE) for the treatment of esophageal squamous
      cell carcinoma (ESCC). METHODS: A total of 105 patients who underwent RE (n=62)
      or TE (n=43) due to ESCC were included in this study. Early postoperative
      outcomes and long-term survivals between the two groups were compared. RESULTS:
      The RE and TE groups were comparable in preoperative clinical characteristics.
      Total operation times were not significantly different between the two groups
      (490 minutes in RE vs. 458 minutes in TE; P=0.118). The total number of dissected
      lymph nodes was significantly greater in the RE group (37.3+/-17.1 vs. 28.7+/
      11.8; P=0.003), and intergroup differences were significant for numbers of lymph
      nodes dissected from the upper mediastinum (10.7+/-9.7 in RE vs. 6.3+/-9.3 in TE;
      P=0.032) and the abdomen (12.2+/-8.7 in RE vs. 7.8+/-7.1 in TE; P=0.007). Five
      year overall survival was not different between the two groups (69% in RE and 59%
      in TE; P=0.737). CONCLUSIONS: Better quality lymphadenectomy could be achieved in
      RE although survival benefit was not clear. Prospective randomized studies
      comparing the RE and TE are necessary.

PMID- 27867560
TI  - Should primary tumor be resected for non-small cell lung cancer with malignant
      pleural disease unexpectedly found during operation?-a systemic review and meta
      analysis.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) with malignant pleural disease
      (MPD) was considered to be contraindication for surgery, but sometimes MPD was
      unexpectedly found intraoperatively. There was no consensus on the role of
      surgical intervention on the primary tumor in patients with MPD. The object of
      this research was to assess whether exairesis of primary tumor could prolong
      survival time. METHODS: A systemic research of literature was performed on the
      databases of PubMed, Embase and Web of Science. Literatures examining surgical
      benefit or other prognostic factors among NSCLC patients with MPD unexpectedly
      found during operations were included. Hazard ratio (HR) with 95% confidence
      interval (95% CI) as well as P value is applied for prognostic role of surgical
      removal or other potential factors. RESULTS: Nine articles with a total number of
      861 patients fulfilled the eligibility criteria, five of them compared the
      survival benefit between exploration and resection among NSCLC patients with
      unexpected MPD, and other studies also investigated the prognostic factors in
      these patients. There was a significant survival benefit in patients with primary
      tumor resection (HR =0.443; 95% CI: 0.344-0.571; P<0.001). This role was further
      detected when stratified by analysis method and ethnicity. Female was an
      independent favorable predicted factor (HR =0.788; 95% CI: 0.648-0.959; P=0.017)
      while higher N-stage was a risk factor (HR =1.879; 95% CI: 1.307-2.701; P=0.001).
      Among patients who received primary tumor resection, higher N-stage was also a
      risk factor for poorer survival (HR =2.021; 95% CI: 1.496-2.730; P<0.001).
      CONCLUSIONS: Resection of primary tumor, female and lower-N stage were suggested
      to be beneficial prognostic factor among NSCLC patients who were detected with
      MPD for the first time in the operating room. And among these people who received
      surgical removal of primary tumor, lower N-stage also indicated a better
      survival.

PMID- 27867562
TI  - Analysis of risk factors for and the prognosis of postoperative acute respiratory
      distress syndrome in patients with Stanford type A aortic dissection.
AB  - BACKGROUND: To explore the risk factors for and the prognosis of postoperative
      acute respiratory distress syndrome (ARDS) in patients with Stanford type A
      aortic dissection (AD). METHODS: This retrospective nested case-control study
      included 527 Stanford type A AD patients who were divided into ARDS groups and
      non-ARDS groups. The clinical features of the groups were examined. RESULTS: The
      fifty-nine patients in the ARDS group exhibited extended durations of
      cardiopulmonary bypass (CPB) (P=0.004), deep hypothermic circulatory arrest
      (DHCA) (P=0.000), ventilator support (P=0.013) and intensive care unit (ICU) stay
      (P=0.045), higher hospital costs (P=0.000), larger perioperative transfusions
      volumes [red blood cells (RBC): P=0.002, platelets (PLT): P=0.040, fresh frozen
      plasma (FFP): P=0.001], more frequent pulmonary infection (P=0.018) and multiple
      organ dysfunction syndrome (MODS) (P=0.040) and a higher rate of in-hospital
      mortality (P=0.020). The ARDS group exhibited worse statuses in terms of
      oxygenation index (OI) values (P=0.000) and Apache II scores (P=0.000). DHCA
      [P=0.000, odds ratio (OR) =2.589] and perioperative transfusion (RBC: P=0.000, OR
      =2.573; PLT: P=0.027, OR =1.571; FFP: P=0.002, OR =1.929) were independent risk
      factors for postoperative ARDS. The survival rates and median survival times
      after discharge were similar between the two groups (P=0.843). CONCLUSIONS: DHCA
      duration and perioperative transfusion volume were independent risk factors for
      postoperative ARDS which warrants greater attention by the cardiac surgeons.

PMID- 27867563
TI  - Single-port video-assisted thoracic surgery in the treatment of non-small cell
      lung cancer: a propensity-matched comparative analysis.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS)-assisted lobectomy is widely
      used to treat non-small cell lung carcinoma (NSCLC). There are no reports
      concerning the comparison between single-port VATS and two-port VATS in treating
      NSCLC. This study aimed to compare the perioperative and short-term follow-up
      results between these two methods for treating NSCLC. METHODS: A retrospective
      surgical evaluation of patients undergoing either single-port VATS or two-port
      VATS for NSCLC between January 2013 and June 2015 was conducted. The propensity
      score (PS) matching method was used to reduce selection bias by creating two
      groups. After generating the PSs, 1:1 ratio and nearest-neighbor score matching
      was completed. The primary outcome measures were surgical time, blood loss,
      drainage time, length of hospital stay, postoperative pain score and patient
      satisfaction score. The data were analyzed statistically with P<0.05 defined as
      statistically significant. RESULTS: Of the 143 patients who met the inclusion
      criteria, 66 (46.2%) were operated on using two-port VATS and 77 (53.8%) using
      single-port VATS. After 1-to-1 PS matching, 63 pairs were selected. Both groups
      were well balanced for age, gender, body mass index, pulmonary function,
      preoperative comorbidity, tumor size and tumor type. The single-port VATS group
      had less blood loss, less postoperative pain, and a higher satisfaction score
      than those in the two-port VATS group, with statistical significance.
      Postoperative complications occurred in 2 (2/63, 3.2%) patients in the single
      port VATS group and 6 (6/63, 9.5%) patients in the two-port VATS group, not a
      significant difference. No deaths occurred during the follow-up period.
      CONCLUSIONS: A single-port VATS-assisted lobectomy is suggested to be safe and
      feasible for treating NSCLC. Compared with two-port VATS, single-port VATS has
      many advantages, including reduced blood loss, less postoperative pain and a
      higher satisfaction score.

PMID- 27867564
TI  - Psychological impact of revealing a diagnosis of lung cancer to patients in
      China.
AB  - BACKGROUND: In conventional Chinese culture, awareness of a malignant disease is
      believed to increase a patient's psychological pressure, leading to anxiety or
      depression. But this notion is in conflict with the patient's right to receive
      information about their own disease. METHODS: This study is to investigate
      whether disclosure of diagnosis increases the level of anxiety or depression in
      patients diagnosed with lung cancer. Seventy patients who underwent lung
      resection and diagnosed with lung cancer postoperatively were divided into two
      groups-the disclosed group (n=35) and the undisclosed group (n=35), depending on
      the awareness of their diagnosis, as decided by their consigned family members.
      All patients were asked to fill in a form to evaluate their level of anxiety and
      depression before discharge. RESULTS: Disclosure of diagnosis did not affect the
      degree of anxiety or depression in patients with lung cancer (P>0.05). Age <=50,
      relatively more advanced stage (stage II as compared with stage I) of disease,
      extensive surgery and major postoperative complication were risk factors of
      anxiety (P<0.05). Major postoperative complication was the only risk factor of
      depression (P<0.05). CONCLUSIONS: Disclosure of diagnosis to patients with lung
      cancer does not induce or aggravate anxiety or depression in modern Chinese
      population. Factors such as complications, age, stage of disease and extent of
      surgery do have psychological impacts on patient with lung cancer.

PMID- 27867565
TI  - Changes in cholesterol level correlate with the course of pulmonary
      nontuberculous mycobacterial disease.
AB  - BACKGROUND: Nutritional assessment is important in patients with pulmonary
      nontuberculous mycobacterial (PNTM) disease. The therapeutic effect of a
      cholesterol-rich diet in tuberculosis (TB) patients has been demonstrated, but
      the role of cholesterol in PNTM disease is unclear. This study evaluated the
      sequential changes in nutritional markers, including cholesterol, total
      lymphocyte count and visceral fat volume, according to the PNTM disease course.
      METHODS: This was an age-, sex- and number of comorbid diseases-matched case
      control analysis of 89 patients with PNTM disease and 356 controls, who were
      participants in a Korean national survey. RESULTS: The median body mass index
      (BMI) and cholesterol level in the PNTM group [BMI =19.7 kg/m2; interquartile
      range (IQR): 17.8-21.6; cholesterol: 159 mg/dL; IQR, 135-185] were lower than
      those in controls (BMI: 23.1 kg/m2; IQR, 21.3-25.3; cholesterol: 188 mg/dL; IQR,
      164-217; both P<0.001). In a multivariate analysis, Age more than 70 years (OR
      =3.38; 95% CI: 1.13-10.15, P=0.029), BMI <19.5 kg/m2 (OR =5.09; 95% CI: 1.67
      15.48; P=0.004) and cavitary lesions (OR: 3.86; 95% CI: 1.30-11.47; P=0.015) were
      independently associated with extensive pulmonary lesions involving more than
      four lobes. The total cholesterol level, total lymphocyte count showed a tendency
      to decrease in PNTM patients with disease progression (both, P value <0.05), but
      not in those with a stable disease course. A decrease in cholesterol
      concentration of >20 mg/dL and a decrease in lymphocyte count more than 200/uL
      were predictive factors for disease progression (cholesterol: OR =10.50, 95% CI:
      2.51-43.98, P=0.001; lymphocyte count: OR =5.32, 95% CI: 1.46-19.35, P=0.011).
      CONCLUSIONS: These findings suggest that the change in cholesterol level may be a
      marker of disease progression in patients with PNTM disease.

PMID- 27867566
TI  - Effectiveness of temporary positive expiratory pressure (T-PEP) at home and at
      hospital in patients with severe chronic obstructive pulmonary disease.
AB  - BACKGROUND: Temporary positive airway pressure (T-PEP) is a tool recently
      introduced in the treatment of chronic obstructive pulmonary disease (COPD) or
      bronchiectasis. It demonstrated encouraging results also in severe COPD patients.
      The aim of this study is verify if adding T-PEP to best bronchodilator therapy
      both in clinic and home administering could reduce disease exacerbations and
      improve lung function in patients with severe COPD. METHODS: A total of 142
      patients with severe COPD (FEV1 <50%) were enrolled; 120 were randomized in three
      groups: a group treated with T-PEP at home, a group with T-PEP at hospital and a
      group with medical therapy only (control group). Number of acute exacerbations
      COPD (AECOPD) after 1 month and 3 months were the primary outcomes. Secondary
      outcomes were changes in respiratory function parameters (FVC, FEV1, TLC, RV),
      arterial blood gases, dyspnea and health status assessment scales (Modified
      Medical Research Council (MMRC), Breathlessness, Cough and Sputum scale (BCSS)
      and COPD Assessment Test (CAT). The time of daily use of the T-PEP was registered
      as well as its acceptance using a Likert scale. RESULTS: Ninety-nine patients
      completed the study. Both the groups who used T-PEP showed a statistical lower
      number of AECOPD after 1 month and 3 months (P<0.01). Some respiratory functional
      parameters improved in the two groups treated with T-PEP (FVC, FEV1, RV) (P<0.02)
      and dyspnea and health status assessment scales (MMRC, BCSS, CAT) (P<0.04;
      P<0.01; P<0.009). The time of daily using was similar in the two T-PEP groups.
      Patients treated at home showed a greater acceptance than those treated at
      hospital (Likert scale 4.7 vs. 5.9) (P<0.01). CONCLUSIONS: Patients treated with
      T-PEP showed a lower number of AECOPD. T-PEP improves functional respiratory
      parameters and improves dyspnea and health status assessment scales. No adherence
      difference in hospital and home treatment was found. Patients preferred home
      treatment.

PMID- 27867567
TI  - Influence of old pulmonary tuberculosis on the management of secondary
      spontaneous pneumothorax in patients over the age of 70 years.
AB  - BACKGROUND: This study aimed to investigate the treatment outcomes and influence
      of old pulmonary tuberculosis (TB) in elderly patients (over 70 years) with
      secondary spontaneous pneumothorax (SSP). METHODS: A retrospective analysis was
      performed on patients with SSP between January 2002 and December 2014. Treatment
      outcomes including chest tube duration (CTD), type and complication of surgery,
      recurrence and survival rate were obtained from the review of medical records and
      analyzed statistically. RESULTS: Two hundred and sixteen consecutive cases were
      recruited. Of these, 134 (62.0%) did not have old pulmonary TB [non-tuberculosis
      (NTB) group], and the other 82 (38.0%) had experienced pulmonary TB (TB group).
      More thoracoscopic surgeries had been performed in the NTB group (P=0.038). More
      postoperative complications developed in the TB group (P=0.038). Total CTD and
      postoperative CTD in the TB group were significantly longer (P=0.015 and 0.030,
      respectively). However, recurrence-free survival and overall survival rate were
      not significantly different between the TB and NTB groups. CONCLUSIONS: Old
      pulmonary TB in elderly patients with SSP made their treatment more complicated.
      However, surgery might be considered in highly selected patients regardless of
      old pulmonary TB, and could be conducted with acceptable morbidity and mortality.

PMID- 27867569
TI  - Does 11.5 mm guided single port surgery has clinical advantage than multi-port
      thoracoscopic surgery in spontaneous pneumothorax?
AB  - BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been widely used for
      spontaneous pneumothorax (SP). In recent years, thoracic surgeons have attempted
      single incision or single port surgery with the development of surgical
      technology and skills. Theoretically, single port surgery is expected to provide
      benefits such as less pain and early recovery. The purpose of this study was to
      determine the benefits of single port surgery in SP. METHODS: The 107 patients
      with SP who underwent surgery, between July 2013 and May 2015, were reviewed
      retrospectively. The patients with secondary pneumothorax, who underwent open
      procedures and lacking of medical records were excluded. Visual analog scale
      (VAS), paresthesia and clinical outcomes were reviewed in 86 patients (46
      patients: three-port, 40 patients: 11.5 mm guided single-port). RESULTS: The mean
      age was 23.4 years in three-port and 22.4 in single-port (P=0.247). The height
      and body weight were not significantly difference between two groups. The mean
      operation time was 39 minutes (mins) in the three-port and 37.3 mins in the
      single port without statistical difference (P=0.204). The pain score in the
      single port surgery was significantly lower after postoperative day (POD) 1
      (P=0.028). However chest tube duration time was significantly shorter in the
      single port group (P<0.001). After exclusion of the patients with chest tube
      removal within postoperative 1 day, the pain score was not significantly
      different at the POD 1 between two groups (P=0.176). The pain score between two
      groups were not different at 1 week after discharge. CONCLUSIONS: The pain score
      reduction was found 1 day after operation in the single port group. However, the
      chest tube duration time was significantly shorter in the single port group and
      the pain score was not different at 1 week after discharge. Considering young age
      in primary SP, the benefit of single port surgery in SP was minimal.

PMID- 27867570
TI  - Small cervical incision facilitates minimally invasive resection of non-invasive
      thoracic inlet tumor.
AB  - BACKGROUND: A challenge for resection of thoracic inlet tumors lies in that high
      risk of injuring vital blood vessels and brachial plexus still exists during the
      resection. And the standard surgical approach for resection of thoracic inlet
      tumors has not yet been well established. METHODS: Small cervical incision
      assisted minimally invasive surgical technique was developed and carried out in
      patients with non-invasive thoracic inlet tumor in our department. RESULTS: We
      successfully performed the small cervical incision-assisted minimally invasive
      surgery in two patients with thoracic inlet tumors. The thoracic inlet tumors of
      the two patients were removed completely without any postoperative complications,
      and the patients achieved quick rehabilitation after surgery. This combined
      approach compensates the blind area of thoracoscope in visualizing the superior
      end of thoracic inlet tumors, and thus enables us to complete the resection
      safely and confidently. CONCLUSIONS: Small cervical incision did facilitate the
      minimally invasive resection of non-invasive thoracic inlet tumor. Hopefully,
      this combined approach of video-assisted thoracoscopic surgery (VATS) with small
      cervical incision could be widely utilized in resecting thoracic inlet tumors by
      general thoracic surgeon.

PMID- 27867568
TI  - The overexpression of KIFC1 was associated with the proliferation and prognosis
      of non-small cell lung cancer.
AB  - BACKGROUND: The kinesin family member C1 (KIFC1, also known as HSET) is a kinesin
      superfamily protein (KIFs). Although KIFC1 acts as a crucial role in the
      development of several human cancers, the KIFC1 expression profile and functional
      remain unclear in non-small cell lung cancer (NSCLC). METHODS: We collected the
      fresh NSCLC samples and paired normal lung tissue in patients with lung cancer
      operation, and detected KIFC1 expression using quantitative reverse-transcription
      polymerase chain reaction (qRT-PCR) and Western blotting. To expand on previous
      smaller-scale studies, NSCLC tissue microarrays (TMA) were analyzed by IHC.
      Finally, cell lines were employed to further probe the potential mechanisms.
      RESULTS: In this study, we described that KIFC1 was significantly upregulated in
      NSCLC tissues compared with the corresponding normal tissues. Moreover, KIFC1
      overexpression was associated with the poor overall survival (OS) of NSCLC
      patients, and siRNA-mediated knockdown of KIFC1 significantly suppressed tumor
      cell proliferation in vitro. Further verification showed that inhibition of KIFC1
      gene expression caused the upregulation of the cyclin-dependent kinases inhibitor
      p21 and downregulation of the cell cycle driver protein cdc2, which arrested
      cells in the G2-M phase. CONCLUSIONS: we report that increased KIFC1 expression
      may promote cell proliferation and identified it as a biomarker of unfavorable
      prognosis in NSCLC patients.

PMID- 27867571
TI  - Role of oxidative stress and outcome of various surgical approaches among
      patients with bullous lung disease candidate for surgical interference.
AB  - BACKGROUND: Bullous lung disease is characterized by formation of blebs, bullae
      and emphysema. We investigate the role of oxidative stress in the pathogenesis of
      bullous lung disease and compare between conventional thoracotomy versus video
      assisted thoracoscopic approach in surgical management of such patients. METHODS:
      This study was a prospective case control study and it was carried out on 21
      patients (16 males and 5 females) with bullous lung disease selected as candidate
      for surgical interference. This was in addition to 21 apparently healthy age and
      sex matched subjects selected as control group. Plasma levels of alpha1
      antitrypsin were estimated using commercially available ELISA assay kit, while
      plasma levels of malondialdehyde (MDA), beta-carotene, vitamin A, vitamin C and
      vitamin E were estimated using spectrophotometric methods. Conventional
      thoracotomy approach was done in thirteen patients, while, videothoracoscopic
      approach was done in eight patients. RESULTS: There were significant higher
      plasma levels of MDA (P<0.001) and lower plasma levels of beta-carotene (P<0.01),
      vitamin A, vitamin C and vitamin E (P<0.001 for each) among patients with bullous
      lung disease when compared with the control group. There was non-significant
      difference regarding the air leakage and the hospital stay among patients with
      bullous lung disease who managed via conventional thoracotomy approach when
      compared with those managed via videothoracoscopic approach. CONCLUSIONS: This
      study proves that the oxidative stress plays an important role in the
      pathogenesis of bullous lung disease. Also there are no significant outcome
      differences between conventional thoracotomy versus video assisted thoracoscopic
      approach in surgical treatment of such patients.

PMID- 27867572
TI  - The efficacy of specific neuromodulators on human refractory chronic cough: a
      systematic review and meta-analysis.
AB  - BACKGROUND: There have been several published reports on the use of orally
      administered, specific centrally acting medicines for the treatment of idiopathic
      cough; however, there is no extant systematic review of randomized controlled
      trials (RCTs) that evaluated their efficacy and safety for the treatment of
      idiopathic cough in human beings. METHODS: We conducted a series of definitive
      systematic reviews and meta-analyses of RCTs. Claims data from the MEDLINE,
      EMBASE, LILACS, CBM, CNKI, VIP, Wan Fang, and Cochrane Library databases were
      used. We also reviewed articles and reference lists of relevant articles
      pertaining to human subjects published prior to March 26, 2016. No language
      restrictions were imposed. Two authors independently reviewed the titles and
      abstracts of the retrieved studies, which were matched using Review Manager 5.3
      software. Disagreements were resolved by consensus. The outcome data were the
      number of subjects whose symptoms declined, measured by cough or Leicester Cough
      Questionnaire (LCQ) score. Random effect meta-analyses were used to pool the
      findings. Publication bias was assessed using funnel plots. RESULTS: Three RCTs,
      regarding the medicines baclofen, amitriptyline, and gabapentin, were conducted
      involving 92 persons in total. Our reviews confirmed that baclofen,
      amitriptyline, and gabapentin show promise in the treatment of cough for select
      cases of refractory chronic cough. After-treatment relief of cough symptoms was
      significant (risk ratio =2.41; 95% CI: 1.15-5.04, n=84). Each of the medicines
      was well tolerated with minimal side effects. Methodological biases in the design
      and execution of cluster randomized trials might contribute to any selection bias
      in this review. CONCLUSIONS: Baclofen, amitriptyline, and gabapentin may be
      effective 'non-specific' antitussives in clinical settings, although none of them
      are used in medical assessments or routinely included in the anatomic diagnostic
      protocol.

PMID- 27867573
TI  - "Ipsilateral, high, single-hand, sideways"-Ruijin rule for camera assistant in
      uniportal video-assisted thoracoscopic surgery.
AB  - Camera assistant plays a very important role in uniportal video-assisted
      thoracoscopic surgery (VATS), who acts as the eye of the surgeon, providing the
      VATS team with a stable and clear operating view. Thus, a good assistant should
      cooperate with surgeon and manipulate the camera expertly, to ensure eye-hand
      coordination. We have performed more than 100 uniportal VATS in the Department Of
      Thoracic Surgery in Ruijin Hospital. Based on our experiences, we summarized the
      method of holding camera, known as "ipsilateral, high, single-hand, sideways",
      which largely improves the comfort and fluency of surgery.

PMID- 27867574
TI  - Non-grasping en bloc mediastinal lymph node dissection through uniportal video
      assisted thoracic surgery for lung cancer surgery.
AB  - Uniportal video-assisted thoracic surgery (VATS) has been demonstrated to be
      feasible, safe, and effective for lung cancer surgery compared with traditional
      multi-portal VATS. However, complete mediastinal lymph node dissection (MLND)
      through uniportal VATS is still a difficult work due to more limited access, and
      most thoracic surgeons use strategies of grasping, accompanied with which are
      complicated instrumentation and mutual interference among them. To simplify the
      instrumentation and make MLND more comfortable, we developed the method of "non
      grasping en bloc MLND" and applied it during uniportal VATS lung cancer surgery.
      Two main instruments (suction and energy devices) were developed with diversified
      use. And only the two instruments were used during MLND following the strategy of
      "non-grasping". This technique incorporates with several advantages, such as:
      simplified instrumentation, decreased risk of damages to lymph nodes, and en bloc
      dissection. Considering the limited access, this technique fits well with the
      uniportal procedure and truly interprets the concept of "less is more" during
      uniportal VATS MLND.

PMID- 27867575
TI  - Stepwise approaches to optimize strategy for holding thoracoscope during single
      port video-assisted thoracoscopic surgery.
AB  - Coordination between the thoracoscope assistant and the surgeon was difficult
      during single port video-assisted thoracoscopic surgery (SP-VATS). What's more,
      holding the thoracoscope was an exhausting work for the assistant and optimized
      strategies were intensely needed. This paper aims to share our experience in
      making the thoracoscope assistant feel comfortable by illustrating the stepwise
      approaches in optimizing the strategies for holding the thoracoscope during our
      practice of SP-VATS. The evolution of techniques were divided into four stages:
      stage I, traditional 10-mm 30 degrees  thoracoscope placed at the posterior part
      of the incision; stage II, 5-mm thoracoscope towed and fixed via a silk suture;
      stage III, 5-mm thoracoscope placed outside of a plastic wound protector; stage
      IV, 5-mm thoracoscope introduced into the thoracic cavity through a 5-mm
      laparoscopic trocar outside of a plastic wound protector and the assistant stood
      at a foot-stool. After stepwise improvement, the thoracoscope assistant felt more
      labor saving and comfortable, and coordination with the surgeon has become
      smoother.

PMID- 27867576
TI  - Resection with preserved histologic morphology of a rare tumour via bronchoscopic
      cryosurgery.
AB  - Tracheobronchial leiomyoma is a rare pulmonary neoplasm accounting for <2% of
      benign tumours of the lower airway. Published case series reported bronchoscopic
      resectability with laser ablation for lesions located in the large airway.
      Surgery was performed for tumours with wide-based and tumours located in
      segmental bronchus or lung parenchyma. This is the first reported case of
      complete bronchoscopic cryoresection of leiomyoma arising from the subsegmental
      bronchi and illustrating the cryopreservation of its histologic morphology. A 55
      year-old Chinese male who was a life-long non-smoker presented with chronic
      cough, left-sided chest pain and loss of weight. Chest radiograph showed left
      lower lobe (LLL) collapse, with the accompanying computed tomography scan of the
      thorax showing a non-enhancing soft tissue lesion in the LLL bronchus. Rigid
      bronchoscopy was performed, with rigid forceps resection followed by cryosurgery
      of the tumour to its base. Histology was consistent with a primary bronchial
      leiomyoma. Surveillance bronchoscopy performed 6 months later revealed no tumour
      recurrence. The patient also had complete resolution of his symptoms. Cryosurgery
      is a promising treatment modality, in complement with conventional forceps
      resection, for benign airway neoplasms.

PMID- 27867577
TI  - When continuous positive airway pressure (CPAP) fails.
AB  - Obstructive sleep apnoea (OSA) is increasingly prevalent, particularly in the
      context of the obesity epidemic, and is associated with a significant social,
      health and economic impact. The gold standard of treatment for moderate to severe
      OSA is continuous positive airway pressure (CPAP). However compliance rates can
      be low. Methodology to improve patient tolerance to CPAP alongside with
      alternative, non-surgical and surgical, management strategies are discussed. All
      patients that fail CPAP therapy would benefit from formal upper airway evaluation
      by the otolaryngologist to identify any obvious causes and consider site-specific
      surgical therapies. Patient selection is integral to ensuring successful
      outcomes. A multidisciplinary team is needed to manage these patients.

PMID- 27867579
TI  - Three-field lymph node dissection in treating the esophageal cancer.
AB  - There are many controversies in lymphadenectomy for thoracic esophageal cancer,
      and whether 3-field lymphadenectomy or 2-field lymphadenectomy is better have
      still been in doubt. The aim of this article is to review the role of the lymph
      node dissection by introducing the merits and demerits in 3-field
      lymphadenectomy, and the development in lymphadenectomy's selection, treatment
      and diagnosis. All the literatures related to esophageal lymphadenectomy and
      minimally invasive surgery (MIE) were searched in PubMed database and the cross
      references were added and reviewed to complete the reference list. Several
      researches elucidated that better overall survival (OS) in patients with
      esophageal cancer after 3-field lymphadenectomy had been reported worldwide, and
      3-field lymphadenectomy is more suitable for treating esophageal cancer with
      cervical and/or upper mediastinal lymph nodes metastasis than 2-field
      lymphadenectomy regardless of the tumor's histology and location. Many approaches
      based on the characteristics of esophageal cancer lymph node metastasis are taken
      to improve the accuracy of 3-field lymphadenectomy and decrease the postoperative
      morbidity and mortality, while every approach needs further studies to
      demonstrate its feasibility. The benefits of the recently rapid-developed
      techniques performed in treating esophageal cancer: the MIE and the robotic
      assisted thoracoscopic esophagectomy are illuminated as well, and both of them
      are technically safe and feasible for esophageal cancer, whereas further
      evaluations are still necessary.

PMID- 27867578
TI  - Relationships between chronic obstructive pulmonary disease and lung cancer:
      biological insights.
AB  - Lung cancer (LC) has become one of the leading causes of preventable death in the
      last few decades. Cigarette smoking (CS) stays as the main etiologic factor of LC
      despite that many other causes such as occupational exposures, air pollution,
      asbestos, or radiation have also been implicated. Patients with chronic
      obstructive pulmonary disease (COPD), which also represents a major cause of
      morbidity and mortality in developed countries, exhibit a significantly greater
      risk of LC. The study of the underlying biological mechanisms that may predispose
      patients with chronic respiratory diseases to a higher incidence of LC has also
      gained much attention in the last few years. The present review has been divided
      into three major sections in which different aspects have been addressed: (I)
      relevant etiologic agents of LC; (II) studies confirming the hypothesis that COPD
      patients are exposed to a greater risk of developing LC; and (III) evidence on
      the most relevant underlying biological mechanisms that support the links between
      COPD and LC. Several carcinogenic agents have been described in the last decades
      but CS remains to be the leading etiologic agent in most geographical regions in
      which the incidence of LC is very high. Growing evidence has put the line forward
      the implications of COPD and especially of emphysema in LC development. Hence,
      COPD represents a major risk factor of LC in patients. Different avenues of
      research have demonstrated the presence of relevant biological mechanisms that
      may predispose COPD patients to develop LC. Importantly, the so far identified
      biological mechanisms offer targets for the design of specific therapeutic
      strategies that will further the current treatment options for patients with LC.
      Prospective screening studies, in which patients with COPD should be followed up
      for several years will help identify biomarkers that may predict the risk of LC
      among these patients.

PMID- 27867580
TI  - Understanding and managing in-stent restenosis: a review of clinical data, from
      pathogenesis to treatment.
AB  - The lumen diameter reduction after percutaneous coronary intervention (PCI) is
      well known as "restenosis". This phenomenon is due to vessel remodeling/recoil in
      case of no-stent strategy or, in case of stent employ, "neointimal proliferation"
      that consists in an excessive tissue proliferation in the luminal surface of the
      stent otherwise by a further new-occurring atherosclerotic process called
      "neoatherosclerosis". The exact incidence of in-stent restenosis (ISR) is not
      easy to determine caused by different clinical, angiographic and operative
      factors. In the pre-stent era the occurrence of restenosis ranged between 32-55%
      of all angioplasties, and drop to successively 17-41% in the bare metal stents
      (BMS) era. The advent of drug-eluting stent (DES), especially 2nd generation, and
      drug-coated balloon (DCB) further reduce restenosis rate until <10%. We here
      review the main characteristics of this common complication of coronary
      interventions, from its pathogenesis to the most appropriate treatment strategy.

PMID- 27867581
TI  - The diseases of airway-tracheal diverticulum: a review of the literature.
AB  - Tracheal diverticulum (DV) is a type of paratracheal air cyst (PTAC) that is
      often asymptomatic and usually detected incidentally by imaging methods. Tracheal
      DV are divided into two subgroups: congenital and acquired. Dysphagia,
      odynophagia, neck pain, hoarseness, hemoptysis, choking, and recurrent episodes
      of hiccups and burping can also be seen in symptomatic patients. Thin-section
      multidetector computed tomography (MDCT) is useful for diagnosis of tracheal
      diverticulum. The relationship between DV and tracheal lumen can be demonstrated
      by axial, coronal, and sagittal reformat multiplanar images. Bronchoscopy can
      also be used in diagnosis for tracheal DV. However, the connection between DV and
      tracheal lumen can not be shown easily with bronchoscopy. Conservative treatment
      is the preferred treatment in asymptomatic patients. Surgical or conservative
      treatment can be performed for symptomatic patients, depending on patient age and
      physical condition.

PMID- 27867582
TI  - Central airway tumors: interventional bronchoscopy in diagnosis and management.
AB  - The diagnosis of central airway tumors is usually challenging because of the
      vague presentations. Advances in visualization technology in bronchoscopy aid
      early detection of bronchial lesion. Cryotechnology has great impact on
      endobronchial lesion sampling and provides better diagnostic yield. Airway tumor
      involvements result in significant alteration in life quality and lead to poor
      life expectancy. Timely and efficiently use ablation techniques by heat or cold
      energy provide symptoms relief for central airway obstruction. Prostheses
      implantation is effective in maintaining airway patency after ablative procedure
      or external compression. Combined interventional bronchoscopy modalities and
      other adjunctive therapies have improvement in quality of life and further
      benefit in survival. This review aims to provide a diagnostic approach to central
      airway tumors and an overview of currently available techniques of interventional
      bronchoscopy in managing symptomatic central airway obstruction.

PMID- 27867584
TI  - Birt-Hogg-Dube syndrome accompanied by pulmonary arteriovenous malformation.
AB  - A 25-year-old male with Birt-Hogg-Dube (BHD) syndrome who developed hemothorax
      caused by ruptured of pulmonary arteriovenous malformation was reported. The
      patient was admitted to the hospital due to chest pain. A chest X-ray showed
      pleural fluid in his left lung, and a chest CT showed the presence of a tumor
      with enhanced contrast in the lower left lobe of approximately 5 cm in a
      diameter. Pleural fluid was collected by tap and indicated the presence of blood;
      therefore, hemothorax was suspected. Thoracoscopic surgery was performed to
      remove the mass for homostasis. Pathological findings indicated that the resected
      tumor-like lesion was an intrapulmonary hematoma, and aggregated vascular vessels
      of various diameters forming incomplete media elastic lamina was observed around
      the hematoma; therefore, it was diagnosed as pulmonary arteriovenous
      malformation. Family history of the patient indicated the presence of
      pneumothorax and malignant diseases, and the patient presented with papules and
      multiple pulmonary cysts. The genetic test revealed a deletion of exon 11 of the
      BHD gene; therefore, the patient was diagnosed with BHD syndrome. This report is
      the first to describe BHD syndrome accompanied by pulmonary arteriovenous
      malformation.

PMID- 27867583
TI  - Acute respiratory distress syndrome after cardiac surgery.
AB  - Acute respiratory distress syndrome (ARDS) is a leading cause of postoperative
      respiratory failure, with a mortality rate approaching 40% in the general
      population and 80% in the subset of patients undergoing cardiac surgery. The
      increased risk of ARDS in these patients has traditionally been associated with
      the use of cardiopulmonary bypass (CPB), the need for blood product transfusions,
      large volume shifts, mechanical ventilation and direct surgical insult. Indeed,
      the impact of ARDS in the cardiac population is substantial, affecting not only
      survival but also in-hospital length of stay and long-term physical and
      psychological morbidity. No patient undergoing cardiac surgery can be considered
      ARDS risk-free. Early identification of those at higher risk is crucial to
      warrant the adoption of both surgical and non-surgical specific preventative
      strategies. The present review focuses on epidemiology, risk assessment,
      pathophysiology, prevention and management of ARDS in the specific setting of
      patients undergoing cardiac surgery.

PMID- 27867585
TI  - Successful treatment of suspected organizing pneumonia in a patient with Middle
      East respiratory syndrome coronavirus infection: a case report.
AB  - A 54-year-old man with Middle East respiratory syndrome coronavirus (MERS-CoV)
      infection was transferred to our hospital. We initiated anti-viral drugs and
      supportive care. The patient's fever and chills disappeared 3 days after
      admission and the results of serial follow-up reverse transcription-polymerase
      chain reaction testing for MERS-CoV was negative soon thereafter. He was
      discharged from the hospital 14 days after admission with no symptoms; however,
      he presented with a fever 7 days after discharge and was re-hospitalized. Chest
      radiographs showed newly developed consolidative opacity. His fever persisted for
      3 days after commencing empirical antibiotics. Subsequent contrast-enhanced
      computed tomography (CT) of the chest showed focal patchy airspace consolidation
      and ground-glass opacities (GGOs) in a subpleural lesion of the right lower and
      left upper lobes, which was indicative of organizing pneumonia. We initiated
      empirical corticosteroid treatment for this illness, and his fever markedly
      subsided 1 day later. A chest radiograph showed improvement in the lung lesions,
      and he was discharged from the hospital 10 days after re-admission. The
      corticosteroid dose was gradually tapered over 2 months at the outpatient clinic,
      and a follow-up CT scan showed complete resolution of the consolidation and GGOs.

PMID- 27867586
TI  - Autofluorescence imaging bronchoscopy as a novel approach to the management of
      tracheobronchopathia osteochondroplastica: a case report.
AB  - Tracheobronchopathia osteochondroplastica (TO) is not only rare but also presents
      highly varied and unpredictable clinical manifestations. Consequently, the
      management and treatment strategies remain unclear. An accurate evaluation tool
      is important for the management of individual patients in the absence of standard
      guidelines. Although bronchoscopy is the gold standard for diagnosis, it cannot
      satisfactorily detect the treatment response and disease progression because
      subtle mucosal changes can go undetected. Therefore, improved techniques that can
      detect subtle mucosal changes associated with TO are desirable. Autofluorescence
      imaging bronchoscopy (AFI) is a recently introduced advanced endoscopic
      technology that can detect subtle mucosal changes with the aid of different
      colors. Here we report the first case, to the best of our knowledge, involving a
      42-year-old man with TO in whom tracheal involvement was evaluated by AFI and
      detected as the appearance of a magenta color.

PMID- 27867587
TI  - Acute chest pain in a triathlete: rupture of the noncoronary sinus of Valsalva
      into the right ventricle.
AB  - Sinus of Valsalva (SoV) aneurysm is a rare cardiac disease which can be
      congenital or acquired. A ruptured SoV aneurysm presents a clinical emergency and
      can lead to progressively deteriorating heart failure. Therefore, appropriate
      treatment requires prompt and accurate diagnosis. Most ruptured or nonruptured
      SoV aneurysms are diagnosed by the means of echocardiography. However,
      cardiovascular magnetic resonance (CMR) can provide information on precise
      anatomy and mechanisms due to its excellent soft tissue contrast and high
      resolution, and thereby allows for optimized preoperative planning of the repair
      strategy. In the present case, we demonstrate the benefit of CMR in emergency
      settings.

PMID- 27867588
TI  - An unusual case of incomplete Carney triad: an 18-year-old girl suffering from
      multiple benign tumors.
AB  - Carney triad is a rare syndrome that involves gastrointestinal stromal tumor
      (GIST), pulmonary chondroma and extra-adrenal paraganglioma. Patients presenting
      GIST and pulmonary chondroma account for 72.7% of all incomplete Carney triad
      cases. Clinically, it is mainly diagnosed by radiological images and pathological
      results. Some studies have elucidated the pathogenesis of Carney triad. Surgical
      resection is the preferred treatment for Carney triad. Generally speaking, the
      prognosis of patients with Carney triad has been satisfied. According to current
      reports, the rate of 40-year survival is up to 73%. The case reports an 18-year
      old girl suffering from pulmonary chondroma and posterior mediastinal
      paraganglioma, simultaneously with pulmonary hamartoma, breast fibroma and lower
      limb chondroma.

PMID- 27867589
TI  - Bruton's agammaglobulinemia in an adult male due to a novel mutation: a case
      report.
AB  - X-linked agammaglobulinemia (XLA) is caused by mutation in the gene coding for
      Bruton's tyrosine kinase (BTK), which impairs peripheral B cell maturation and
      hypogammaglobulinemia. In this report, we present a case of XLA in a 22-year-old
      adult male. Genetic testing revealed a novel mutation located at the conserved
      region (c.383T>C). The patient had a history of recurrent respiratory tract
      infection which eventually progressed to chronic type II respiratory failure.
      Several pathogenic bacteria were isolated on culture of respiratory secretions
      obtained on bronchoscopy. The patient improved on treatment with antibiotics.

PMID- 27867590
TI  - Prosthetic valve endocarditis after transcatheter aortic valve implantation
      diagnostic and surgical considerations.
AB  - Prosthetic valve endocarditis (PVE) after transcatheter aortic valve implantation
      (TAVI) or surgical aortic valve replacement (SAVR) is a potential life
      threatening complication. Better understanding of the incidence, predictors,
      clinical presentation, diagnostic measures, complications and management of PVE
      may help improve TAVI long-term outcome. We report a case of TAVI-PVE in an 80
      year-old high risk patient in whom SAVR was successfully performed. We have
      reviewed literature regarding TAVI-PVE.

PMID- 27867591
TI  - Anastomotic leak: an early complication with potentially long-term consequences.

PMID- 27867592
TI  - How to deal with subcentimeter lung cancer: a moving target!

PMID- 27867593
TI  - Duration of dual antiplatelet therapy (DAPT): a call for personalized medicine.

PMID- 27867594
TI  - Onsite cardiac surgery standby during transcatheter aortic valve implantation:
      when and why.

PMID- 27867595
TI  - Significance of depression in family caregivers of critically ill patients
      discharged home.

PMID- 27867596
TI  - Does high-dose perioperative use of statins ameliorate acute kidney injury
      following cardiac surgery?

PMID- 27867597
TI  - From self-awareness to self-actualization: empowering sepsis survivors to a
      meaningful and enduring recovery.

PMID- 27867598
TI  - Timing of RRT initiation in critically-ill patients: time for precision medicine.

PMID- 27867599
TI  - Myocardial revascularization: do age and sex matter?

PMID- 27867600
TI  - Emerging strategies for the treatment of advanced small cell lung cancer.

PMID- 27867601
TI  - Efficacy and safety of nivolumab combined with standard therapies for first-line
      therapy of advanced non-small cell lung cancer.

PMID- 27867602
TI  - Lung cancer screening: not all nodules are created equal.

PMID- 27867603
TI  - Left atrial appendage exclusion for atrial fibrillation: does the protection from
      stroke prevail in the long-term?

PMID- 27867604
TI  - Best percutaneous coronary intervention approach for small caliber coronary
      arteries.

PMID- 27867605
TI  - Should we apply "early" initiation of renal replacement therapy to critically ill
      patients with acute kidney injury?

PMID- 27867606
TI  - Robotic assisted lung resection needs further evidence.

PMID- 27867607
TI  - Liquid biopsy in the practice of neo-oncology.

PMID- 27867608
TI  - Changes in biometry and cerebroplacental hemodynamics in fetuses with congenital
      heart diseases.

PMID- 27867609
TI  - Editorial on the article entitled "brigatinib efficacy and safety in patients
      with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer in a
      phase I/II trial".

PMID- 27867610
TI  - Clinical efficacy of EGFR-TKIs in combination with chemotherapy in patients with
      advanced non-small cell lung cancer harboring EGFR mutations.

PMID- 27867611
TI  - High-flow nasal cannula oxygen therapy: more than a higher amount of oxygen
      delivery.

PMID- 27867612
TI  - New guidelines on duration of dual antiplatelet therapy in patients with coronary
      artery disease: what's the novelty?

PMID- 27867613
TI  - Implementing computed tomography-based lung cancer screening in the community.

PMID- 27867614
TI  - Anti-arrhythmics in out-of-hospital cardiac arrest: lessons from a randomized
      controlled trial.

PMID- 27867616
TI  - Measures of outcome in lung cancer screening: maximising the benefits.

PMID- 27867615
TI  - Current evidence in support of the second-generation anaplastic lymphoma kinase
      (ALK) tyrosine kinase inhibitor alectinib for the treatment of non-small cell
      lung cancer positive for ALK translocation.

PMID- 27867617
TI  - Bleeding in continuous flow left ventricular assist device recipients: an
      acquired vasculopathy?

PMID- 27867618
TI  - Bioresorbable scaffolds and drug-eluting balloons for the management of
      spontaneous coronary artery dissections.

PMID- 27867619
TI  - Editorial on the article entitled "the impact of intimal tear location and
      partial false lumen thrombosis in acute type b aortic dissection".

PMID- 27867620
TI  - Myocarditis with very high troponins: risk stratification by cardiac magnetic
      resonance.

PMID- 27867621
TI  - Von Willebrand factor, paravalvular leak, and a new vista for TAVR.

PMID- 27867622
TI  - Early enteral nutrition still has advantages in patients undergoing
      pancreaticoduodenectomy.

PMID- 27867623
TI  - The APPS: an outcome score for the acute respiratory distress syndrome.

PMID- 27867624
TI  - Immunotherapy and lung cancer: from therapeutic cancer vaccination to novel
      approaches.

PMID- 27867625
TI  - Coronary bifurcation lesions: is less more?

PMID- 27867626
TI  - Perspectives and implications of the new sepsis clinical practice guidelines.

PMID- 27867627
TI  - Endovascular stent graft repair of the ascending aorta-final frontier in the
      endovascular treatment of the aorta.

PMID- 27867628
TI  - Radiosensitivity in the breast cancer management scenario: another step forward?

PMID- 27867629
TI  - A novel function of IL-33: suppression of innate antiviral immunity.

PMID- 27867630
TI  - MELK kinase holds promise as a new radiosensitizing target and biomarker in
      triple-negative breast cancer.

PMID- 27867631
TI  - Optimizing the lung cancer screening interval: the world is waiting.

PMID- 27867632
TI  - The modest outcome of clinical trials with bone marrow cells for myocardial
      repair: is the autologous source of cells the prime culprit?

PMID- 27867633
TI  - A crucial first randomized controlled trial of thymectomy in non-thymomatous
      myasthenia gravis.

PMID- 27867634
TI  - Quality of life in adults with congenital heart disease: what matters?

PMID- 27867635
TI  - Efficacy of crizotinib in ALK fusion variants.

PMID- 27867636
TI  - Oligometastases to the liver: predicting outcomes based upon radiation
      sensitivity.

PMID- 27867637
TI  - Harnessing plasma genotyping for precision therapy against lung cancer.

PMID- 27867639
TI  - Using sound advice-intravascular ultrasound as a diagnostic tool.

PMID- 27867638
TI  - The appropriate use of risk scores in the prediction of atrial fibrillation.

PMID- 27867640
TI  - "The scaffolding must be removed once the house is built"-spontaneous coronary
      artery dissection and the potential of bioresorbable scaffolds.

PMID- 27867641
TI  - Role of adjuvant therapy in early-stage small-cell lung cancer: comment on a
      population-based cohort study of patients with early-stage small-cell lung
      cancer.

PMID- 27867642
TI  - More options, more considerations: how new treatment options influence clinical
      decision making.

PMID- 27867643
TI  - High salt diet and caffeine: food for thought.

PMID- 27867644
TI  - Contemporary drug-eluting stents and companion polymers: durable is not
      synonymous with harm.

PMID- 27867645
TI  - Management of screening-detected stage I lung cancer.

PMID- 27867646
TI  - Commentary on "Randomized trial of thymectomy in myasthenia gravis".

PMID- 27867647
TI  - The omentum flap for empyema treatment: indications and disadvantages.

PMID- 27867648
TI  - Firm evidence of complete revascularization with culprit and target vessel
      revascularization only after ST-segment elevation myocardial infarction.

PMID- 27867649
TI  - Minimising patient harm whilst gaining surgical proficiency.

PMID- 27867650
TI  - Reducing reintubation and postextubation respiratory failure: improving high-flow
      oxygen support performance.

PMID- 27867652
TI  - Is it possible to terminate resuscitation in accordance with the termination of
      resuscitation rule?

PMID- 27867651
TI  - Dexmedetomidine, agitated delirium, and "off-label" drugs.

PMID- 27867653
TI  - Appreciating the shades of gray: a case for Computer-Aided Nodule Assessment and
      Risk Yield (CANARY)-based risk stratification of lung adenocarcinomas.

PMID- 27867654
TI  - Patient-prosthesis mismatch: surgical aortic valve replacement versus
      transcatheter aortic valve replacement in high risk patients with aortic
      stenosis.
AB  - Patient prosthesis mismatch (PPM) can occur when a prosthetic aortic valve has an
      effective orifice area (EOA) less than that of a native valve. A recent study by
      Zorn and colleagues evaluated the incidence and significance of PPM in high risk
      patients with severe aortic stenosis who were randomized to transcatheter aortic
      valve replacement (TAVR) or surgical aortic valve replacement (SAVR). TAVR is
      associated with decreased incidence of severe PPM compared to traditional SAVR
      valves. Severe PPM increases risk for death at 1 year postoperatively in high
      risk patients. The increased incidence of PPM is largely due to differences in
      valve design and should encourage development of newer SAVR valves to reduce risk
      for PPM. In addition more vigorous approaches to root enlargement in small
      annulus should be performed with SAVR to prevent PPM.

PMID- 27867656
TI  - Erratum to cardiac obstruction secondary to metastatic invasion - A rare
      complication of Human Herpes Virus 8-positive plasmablastic lymphoma in acquired
      immunodeficiency syndrome.
AB  - [This corrects the article on p. 425 in vol. 4, PMID: 22934146.].

PMID- 27867655
TI  - Veno-arterial extracorporeal membrane oxygenation (VA ECMO) in postcardiotomy
      cardiogenic shock: how much pump flow is enough?
AB  - Post-cardiotomy cardiogenic shock (PCCS) is a complication of heart surgery
      associated with a poor prognosis: veno-arterial extracorporeal membrane
      oxygenation (VA ECMO) ensures end-organ perfusion while fully replacing heart and
      lung function, though it is associated with unsatisfactory results. Few studies
      have identified reliable predictors of poor prognosis early in the course of
      extracorporeal support. A recent study showed the strong prognostic power of
      urine output in the first 24 hours of VA ECMO in predicting early and late
      mortality of PCCS. Urine output is a commonly collected parameter in all
      intensive care units (ICU) and has a defined role in the diagnosis of acute
      kidney injury (AKI) and is inexpensive. These findings offer the possibility to
      summarize some aspects regarding the adequacy of extracorporeal support early in
      the course of cardiogenic shock and to shed light about cardio-renal interactions
      in ECMO patients. Finally, it is our opinion that a timely implantation of
      mechanical circulatory support in post cardiotomy shock should be considered if
      systemic perfusion is not ensured by low or medium dose inotropic support and
      intra-aortic balloon counterpulsation.

PMID- 27867657
TI  - Method of Quantifying Size of Retinal Hemorrhages in Eyes with Branch Retinal
      Vein Occlusion Using 14-Square Grid: Interrater and Intrarater Reliability.
AB  - Purpose. To describe a method of quantifying the size of the retinal hemorrhages
      in branch retinal vein occlusion (BRVO) and to determine the interrater and
      intrarater reliabilities of these measurements. Methods. Thirty-five fundus
      photographs from 35 consecutive eyes with BRVO were studied. The fundus images
      were analyzed with Power-Point(r) software, and a grid of 14 squares was laid
      over the fundus image. Raters were asked to judge the percentage of each of the
      14 squares that was covered by the hemorrhages, and the average of the 14 squares
      was taken to be the relative size of the retinal hemorrhage. Results. Interrater
      reliability between three raters was higher when a grid with 14 squares was used
      (intraclass correlation coefficient (ICC), 0.96) than that when a box with no
      grid was used (ICC, 0.78). Intrarater reliability, which was calculated by the
      retinal hemorrhage area measured on two different days, was also higher (ICC,
      0.97) than that with no grid (ICC, 0.86). Interrater reliability for five fundus
      pictures with poor image quality was also good when a grid with 14 squares was
      used (ICC, 0.88). Conclusions. Although our method is subjective, excellent
      interrater and intrarater reliabilities indicate that this method can be adapted
      for clinical use.

PMID- 27867658
TI  - Man versus Machine: Software Training for Surgeons-An Objective Evaluation of
      Human and Computer-Based Training Tools for Cataract Surgical Performance.
AB  - This study aimed to address two queries: firstly, the relationship between two
      cataract surgical feedback tools for training, one human and one software based,
      and, secondly, evaluating microscope control during phacoemulsification using the
      software. Videos of surgeons with varying experience were enrolled and
      independently scored with the validated PhacoTrack motion capture software and
      the Objective Structured Assessment of Cataract Surgical Skill (OSACCS) human
      scoring tool. Microscope centration and path length travelled were also evaluated
      with the PhacoTrack software. Twenty-two videos correlated PhacoTrack motion
      capture with OSACCS. The PhacoTrack path length, number of movements, and total
      procedure time were found to have high levels of Spearman's rank correlation of 
      0.6792619 (p = 0.001), -0.6652021 (p = 0.002), and -0.771529 (p = 0001),
      respectively, with OSACCS. Sixty-two videos evaluated microscope camera control.
      Novice surgeons had their camera off the pupil centre at a far greater mean
      distance (SD) of 6.9 (3.3) mm, compared with experts of 3.6 (1.6) mm (p ? 0.05).
      The expert surgeons maintained good microscope camera control and limited total
      pupil path length travelled 2512 (1031) mm compared with novices of 4049 (2709)
      mm (p ? 0.05). Good agreement between human and machine quantified measurements
      of surgical skill exists. Our results demonstrate that surrogate markers for
      camera control are predictors of surgical skills.

PMID- 27867659
TI  - Ganglion Cell-Inner Plexiform Layer, Peripapillary Retinal Nerve Fiber Layer, and
      Macular Thickness in Eyes with Myopic beta-Zone Parapapillary Atrophy.
AB  - Purpose. To assess the correlations of myopic beta-zone parapapillary atrophy
      (beta-PPA) with the optic nerve head (ONH) and retina. Methods. We selected 27
      myopic patients who showed prominent beta-PPA in one eye and no beta-PPA in the
      other eye. We studied their macula, macular ganglion cell-inner plexiform layer
      (mGCIPL), peripapillary retinal nerve fiber layer (pRNFL) thickness, and ONH
      parameters using optical coherence tomography. Results. The average of five out
      of six sectors and minimum values of mGCIPL thicknesses in eyes with prominent
      beta-PPA discs were significantly less than those of the control eyes. The
      results of clock-hour sector analyses showed significant differences for pRNFL
      thickness in one sector. In the ONH analyses, no significant difference was
      observed between myopic beta-PPA and control eyes. The macular thickness of the
      beta-PPA eyes was thinner than control eyes in all sectors. There was a
      significant difference between the two groups in three sectors (the inner
      superior macula, inner temporal macula, and inner inferior macula) but there was
      no significant difference in the other sectors, including the fovea. Conclusions.
      The myopic beta-PPA eyes showed thinner mGCIPL, parafovea, and partial pRNFL
      layers compared with myopic eyes without beta-PPA.

PMID- 27867660
TI  - Corneal Aberrations, Contrast Sensitivity, and Light Distortion in
      Orthokeratology Patients: 1-Year Results.
AB  - Purpose. To evaluate the corneal higher-order aberrations (HOA), contrast
      sensitivity function (CSF), and light distortion (LD) in patients undergoing
      orthokeratology (OK). Methods. Twenty healthy subjects (mean age: 21.40 +/- 8
      years) with mean spherical equivalent refractive error M = -2.19 +/- 0.97 D were
      evaluated at 1 day, 1 month, and 1 year after starting OK treatment. Monocular
      LD, photopic monocular CSF, and corneal HOA for 6 mm pupil size were measured.
      Results. LD showed an increase after the first night (p < 0.05) and recovery to
      baseline after 1 month, remaining stable after 1 year (p > 0.05). Spherical-like,
      coma-like, and secondary astigmatism HOA RMS increased significantly (p <= 0.022)
      from baseline to 1-month visit, remaining unchanged over the follow-up. Contrast
      sensitivity for medium frequencies (3.0, 4.24, and 6.00 cpd) was significantly
      correlated with LD parameters at baseline (r <= -0.529, p < 0.001). However,
      after 1 year of treatment, this correlation was only statistically significant
      for 12 cpd spatial frequency (r <= -0.565, p < 0.001). Spherical-like RMS for 6
      mm pupil size correlated with irregularity of the LD (r = -0.420, p < 0.05) at
      the 1-year visit. Conclusion. LD experienced by OK patients recovers after one
      month of treatment and remains stable in the long term while optical aberrations
      remain significantly higher than baseline.

PMID- 27867661
TI  - Insights into Adherence among a Cohort of Adolescents Aged 12-20 Years in South
      Africa: Reported Barriers to Antiretroviral Treatment.
AB  - Adolescents experience disproportionately high rates of poor ART outcomes
      compared to adults despite prolonged use of antiretroviral therapy in Southern
      African treatment programs, presenting a significant challenge to national
      attempts to meet the UNAIDS 90-90-90 targets for 2020. This cohort study among
      adolescents aged 12-20 years accessing ART care at two urban public-sector
      clinics in Johannesburg between September and November 2013 aimed to identify
      factors potentially associated with poor attendance at clinic visits. Patients
      were followed up through routine medical records to identify missed visits
      (failing to attend clinic within 30 days of scheduled visit date) up to 2 years
      after enrolment. We enrolled 126 adolescents on ART for a median of 6.3 years
      (IQR: 2.7-8.4). A total of 47 (38%) adolescents missed a scheduled visit within
      24 months of enrolment. Older adolescents (18-20 years) were more likely to miss
      a visit compared to adolescents aged 12-14 years (risk ratio (RR) = 1.72; 95% CI:
      1.00-2.95). Those who were identified to have difficulty in taking medication (RR
      = 1.57; 95% CI: 1.13-2.18) as a barrier to care were more likely to miss a visit
      compared to adolescents who did not. Awareness of treatment fatigue, challenges
      to taking ART, and caregiver difficulties is important when considering
      interventions to improve treatment outcomes among adolescents.

PMID- 27867662
TI  - Death Anxiety, Reliability, Validity, and Factorial Structure of the Farsi Form
      of the Arabic Scale of Death Anxiety in Iranian Old-Aged Persons.
AB  - The present study is aimed at examining the level of death anxiety and the sex
      related differences among old-aged Iranian individuals sample to compare the old
      aged persons with young college students and to explore the psychometric
      properties of the Arabic Scale of Death Anxiety (ASDA) factors in old-aged
      sample. A sample of 146 volunteer Iranian individuals took part in the study. The
      mean ages were 68.58 (SD = 7.10), men 68.81 (SD = 7.44) and women 68.28 (SD =
      6.76), respectively. The mean score of the ASDA was 51.09 (SD = 20.19).
      Cronbach's alpha of the ASDA was found to be high (0.94); and Spearman-Brown
      coefficient was 0.92. Women had a significantly higher mean total score on the
      ASDA. Old-aged individuals had a significantly higher mean ASDA total score than
      younger college students (M age = 25.77). The factor analysis of the ASDA items
      yielded three factors accounting for 67.88% of the total variance labeled (F1)
      fear of dead people and tombs; (F2) fear of lethal disease and postmortem events;
      and (F3) death fear. These factors were highly replicable with previous factors
      extracted from a middle-aged Kuwaiti sample. On the basis of the present results,
      there are the following three general conclusions: death anxiety is not
      significantly correlated with age; the sex-related differences on death anxiety
      are striking in the Iranian samples; and the ASDA has a highly replicable factor
      structure among two Iranian and Arab countries.

PMID- 27867663
TI  - Dry Powder Inhalers: A Focus on Advancements in Novel Drug Delivery Systems.
AB  - Administration of drug molecules by inhalation route for treatment of respiratory
      diseases has the ability to deliver drugs, hormones, nucleic acids, steroids,
      proteins, and peptides, particularly to the site of action, improving the
      efficacy of the treatment and consequently lessening adverse effects of the
      treatment. Numerous inhalation delivery systems have been developed and studied
      to treat respiratory diseases such as asthma, COPD, and other pulmonary
      infections. The progress of disciplines such as biomaterials science,
      nanotechnology, particle engineering, molecular biology, and cell biology permits
      further improvement of the treatment capability. The present review analyzes
      modern therapeutic approaches of inhaled drugs with special emphasis on novel
      drug delivery system for treatment of various respiratory diseases.

PMID- 27867664
TI  - The Case for Musical Instrument Training in Cerebral Palsy for
      Neurorehabilitation.
AB  - Recent imaging studies in cerebral palsy (CP) have described several brain
      structural changes, functional alterations, and neuroplastic processes that take
      place after brain injury during early development. These changes affect motor
      pathways as well as sensorimotor networks. Several of these changes correlate
      with behavioral measures of motor and sensory disability. It is now widely
      acknowledged that management of sensory deficits is relevant for rehabilitation
      in CP. Playing a musical instrument demands the coordination of hand movements
      with integrated auditory, visual, and tactile feedback, in a process that
      recruits multiple brain regions. These multiple demands during instrument
      playing, together with the entertaining character of music, have led to the
      development and investigation of music-supported therapies, especially for
      rehabilitation with motor disorders resulting from brain damage. We review
      scientific evidence that supports the use of musical instrument playing for
      rehabilitation in CP. We propose that active musical instrument playing may be an
      efficient means for triggering neuroplastic processes necessary for the
      development of sensorimotor skills in patients with early brain damage. We
      encourage experimental research on neuroplasticity and on its impact on the
      physical and personal development of individuals with CP.

PMID- 27867665
TI  - Dose-Dependent Differential Effect of Neurotrophic Factors on In Vitro and In
      Vivo Regeneration of Motor and Sensory Neurons.
AB  - Although peripheral axons can regenerate after nerve transection and repair,
      functional recovery is usually poor due to inaccurate reinnervation. Neurotrophic
      factors promote directional guidance to regenerating axons and their selective
      application may help to improve functional recovery. Hence, we have characterized
      in organotypic cultures of spinal cord and dorsal root ganglia the effect of
      GDNF, FGF-2, NGF, NT-3, and BDNF at different concentrations on motor and sensory
      neurite outgrowth. In vitro results show that GDNF and FGF-2 enhanced both motor
      and sensory neurite outgrowth, NGF and NT-3 were the most selective to enhance
      sensory neurite outgrowth, and high doses of BDNF selectively enhanced motor
      neurite outgrowth. Then, NGF, NT-3, and BDNF (as the most selective factors) were
      delivered in a collagen matrix within a silicone tube to repair the severed
      sciatic nerve of rats. Quantification of Fluorogold retrolabeled neurons showed
      that NGF and NT-3 did not show preferential effect on sensory regeneration
      whereas BDNF preferentially promoted motor axons regeneration. Therefore, the
      selective effects of NGF and NT-3 shown in vitro are lost when they are applied
      in vivo, but a high dose of BDNF is able to selectively enhance motor neuron
      regeneration both in vitro and in vivo.

PMID- 27867667
TI  - Spontaneous Renal Artery Dissection in a Patient with Neurofibromatosis Type I.
AB  - We present a case of spontaneous renal artery dissection (SRAD) in a 28-year-old
      female with history of neurofibromatosis type I (NF-1) treated successfully with
      endovascular stenting. The clinical presentation, diagnostic testing, and
      treatment options are discussed. An endovascular approach with stenting was
      successfully performed after failure of medical treatment with subcutaneous low
      molecular weight heparin. Patient's blood pressure and symptoms improved
      significantly. This may be the first reported case of SRAD in a patient with NF-1
      successfully treated with endovascular stenting.

PMID- 27867668
TI  - A Rare Clinical Course of Seronegative Pulmonary-Renal Syndrome.
AB  - Purpose. Pulmonary-renal syndrome (PRS) is characterized by diffuse alveolar
      hemorrhage and rapidly progressive glomerulonephritis mainly due to autoimmune
      etiologies. Seronegative PRS is a challenging entity to the clinician, since
      early diagnosis may be missed leading to delayed appropriate treatment. Materials
      and Methods. We present the clinical course of a 77-year-old patient who was
      admitted under the suspected diagnosis of pneumogenic sepsis and septic renal
      failure with fever, dyspnea, and elevated CRP levels. The diagnosis of pulmonary
      renal syndrome was initially missed because of the absence of autoantibodies in
      all serological findings. Results. Despite delayed initiation of
      immunosuppressive therapy and a prolonged period of dialysis and extracorporeal
      membrane oxygenation the patient recovered well and was released to a
      rehabilitation center with nearly normalized creatinine levels. The diagnosis of
      PRS was established by renal biopsy. Conclusion. This case illustrates the
      important differential diagnosis of seronegative pulmonary-renal syndrome in
      patients with pulmonary and renal impairment.

PMID- 27867669
TI  - Simplifying the Treatment of Bone Atrophy in the Posterior Regions: Combination
      of Zygomatic and Wide-Short Implants-A Case Report with 2 Years of Follow-Up.
AB  - The rehabilitation of maxillary and mandibular bone atrophy represents one of the
      main challenges of modern oral implantology because it requires a variety of
      procedures, which not only differ technically, but also differ in their results.
      In the face of limitations such as deficiencies in the height and thickness of
      the alveolar structure, prosthetic rehabilitation has sought to avoid large bone
      reconstruction through bone grafting; this clinical behavior has become a
      treatment system based on evidence from clinical scientific research. In the
      treatment of atrophic maxilla, the use of zygomatic implants has been safely
      applied as a result of extreme technical rigor and mastery of this surgical
      skill. For cases of posterior mandibular atrophy, short implants with a large
      diameter and a combination of short and long implants have been recommended to
      improve biomechanical resistance. These surgical alternatives have demonstrated a
      success rate similar to that of oral rehabilitation with the placing of
      conventional implants, allowing the adoption of immediate loading protocol, a
      decrease in morbidity, simplification and speed of the treatment, and cost
      reduction. This case report presents complete oral rehabilitation in a patient
      with bilateral bone atrophy in the posterior regions of the maxilla and mandible
      with the goal of developing and increasing posterior occlusal stability during
      immediate loading.

PMID- 27867666
TI  - Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi
      Associated Chaperone Protein PIST.
AB  - Protocadherin 15 (PCDH15) is a core component of hair cell tip-links and crucial
      for proper function of inner ear hair cells. Mutations of PCDH15 gene cause
      syndromic and nonsyndromic hearing loss. At present, the regulatory mechanisms
      responsible for the intracellular transportation of PCDH15 largely remain
      unknown. Here we show that PIST, a Golgi-associated, PDZ domain-containing
      protein, interacts with PCDH15. The interaction is mediated by the PDZ domain of
      PIST and the C-terminal PDZ domain-binding interface (PBI) of PCDH15. Through
      this interaction, PIST retains PCDH15 in the trans-Golgi network (TGN) and
      reduces the membrane expression of PCDH15. We have previously showed that PIST
      regulates the membrane expression of another tip-link component, cadherin 23
      (CDH23). Taken together, our finding suggests that PIST regulates the
      intracellular trafficking and membrane targeting of the tip-link proteins CDH23
      and PCDH15.

PMID- 27867670
TI  - Lymphoma Heterogeneity: Three Different Histological Pictures and One Unique
      Clone.
AB  - We report a patient who developed up to three different lymphomas with the same
      clonal IGH rearrangement. She was first diagnosed of splenic zone marginal
      lymphoma and relapsed for the first time with Hodgkin lymphoma histology and
      later with diffuse large B-cell lymphoma histology. Subsequent biopsies and
      analysis of clonally rearranged IGH genes helped to elucidate the clonal
      relationship between the three histologies and to confirm a common origin from
      the three tissue histologies. An integrated diagnosis should always be performed
      in order to achieve the most accurate diagnosis and be able to choose the best
      therapeutic options for our patients.

PMID- 27867671
TI  - Retreatment with Bendamustine-Bortezomib-Dexamethasone in a Patient with
      Relapsed/Refractory Multiple Myeloma.
AB  - The clinical management of relapsed/refractory multiple myeloma and the correct
      choice of the most suitable therapy in heavily pretreated and fragile patients
      are tough clinical issues for clinicians. In advanced phases of disease, the
      choice of available therapies becomes very poor, and the retreatment with
      previously adopted and effective therapy, although unpredictable, could be an
      effective option. In this report, we describe the clinical history of a patient,
      previously treated with 9 lines of therapy, refractory to bortezomib and IMIDs,
      for whom the retreatment with bendamustine resulted in a stable disease with good
      quality of life.

PMID- 27867672
TI  - Primary Angiosarcoma of the Spleen: Rare Diagnosis with Atypical Clinical Course.
AB  - Primary angiosarcoma of the spleen is a rare diagnosis with poor prognosis.
      Morphologically, it demonstrates conventional blood vessel differentiation. We
      present a case of 65-year-old female who underwent radical splenectomy for
      primary angiosarcoma of the spleen. After three-year disease-free interval, she
      was diagnosed with bone-only metastatic disease. Palliative radiotherapy and
      bisphosphonates kept her disease reasonably stable for another four years. After
      development of lung metastases, six cycles of single agent doxorubicin kept her
      progression-free for six years. Upon further progression in lungs, thirteen years
      after original diagnosis, lung biopsy confirmed metastatic splenic angiosarcoma
      in the lungs. She started weekly paclitaxel chemotherapy. Although splenic
      angiosarcoma generally carries grave prognosis, some patients may enjoy prolonged
      periods of disease stabilization. Durable benefit can be achieved in some
      patients with multimodality management. We review the literature focusing on
      systemic treatment for this rare tumor.

PMID- 27867673
TI  - Central Retinal Artery Occlusion in Takayasu's Arteritis as the First
      Presentation of the Disease.
AB  - Takayasu's arteritis (TA) is a chronic inflammatory granulomatous vasculitis
      which affects large and medium arterial vessels. The disease involves especially
      subclavian arteries and aortic branches but it can consist of any arteries. The
      major pathology is granulomatous panarteritis with intima proliferation and
      defects of the elastic lamina of the vessels. We present a case of central
      retinal artery occlusion in TA as the first presentation of the disease. To the
      best of our knowledge, the present case is the first case that demonstrates
      central retinal artery occlusion as an initial manifestation in TA. A 48-year-old
      woman was admitted to our clinic with the complaint of sudden and painless vision
      loss in her right eye for one day. Although retinal artery involvement is a very
      rare presentation in TA, it is important to recall TA particularly in young
      patients with retinal artery occlusion.

PMID- 27867674
TI  - Filariasis of Stensen's Duct: An Index Case.
AB  - Filariasis, a neglected tropical disease, is a global health problem and is
      endemic to 73 countries including India. It is caused by nematodes of
      Filariodidea family, namely, W. bancrofti and B. malayi in India, which have a
      predilection for the lower limbs and testis. We report a never before reported
      case of filariasis of the main parotid duct in a 25-year-old male that resolved
      on medical management, exemplifying the importance of maintaining a high index of
      suspicion and careful examination of cytological smears in endemic countries,
      allowing for an early diagnosis and treatment, decreasing the morbidity of this
      debilitating disease.

PMID- 27867675
TI  - A Case of Thyroid Storm Associated with Cardiomyopathy and Poststreptococcal
      Glomerulonephritis.
AB  - Thyroid storm has a high mortality rate and is often associated with a
      precipitating factor such as intercurrent illness or infection. It is rare in
      pediatric patients. Cardiac disease in hyperthyroidism mostly manifests itself as
      tachycardia but more serious cardiac findings have also been described. A 5-year
      old male with recent strep throat infection presented with dilated
      cardiomyopathy, hematuria, and symptoms and lab findings consistent with severe
      hyperthyroidism. He was diagnosed with thyroid storm secondary to concurrent
      Graves' disease and poststreptococcal glomerulonephritis (PSGN). After starting
      the treatment with methimazole and a beta-blocker, his cardiac disease gradually
      improved and the PSGN resolved over time. There are no specific pediatric
      criteria for thyroid storm. Adult criteria can be difficult to apply to pediatric
      cases. Criteria for diagnosis of thyroid storm are less clear for pediatric
      patients. Dilated cardiomyopathy is a rare cardiac manifestation of
      hyperthyroidism. PSGN is due to glomerular immune complexes and can complicate
      group A strep infection. Providers should be aware of cardiac disease as a
      complication of hyperthyroidism. PSGN should not mechanistically be related to
      hyperthyroidism but can precipitate the signs of thyroid storm such as
      hypertension. This association has not been previously reported in the
      literature.

PMID- 27867676
TI  - Cardiac Magnetic Resonance for Evaluating Catheter Related FDG Avidity.
AB  - A 53-year-old female with a history of metastatic left arm melanoma presented for
      F(18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) which showed a moderately FDG avid focus at her port catheter tip near
      the cavoatrial junction. Although catheter tip related FDG avidity has previously
      been suggested to be bland thrombus or infection, melanoma can metastasize to
      unusual locations including the superior vena cava. In addition, the patient had
      an elevated risk of anticoagulation due to a history of hemorrhagic brain
      metastases. Therefore, confirmatory cardiac magnetic resonance (CMR) was obtained
      and findings were consistent with bland catheter-related thrombus.

PMID- 27867677
TI  - Bilateral Simultaneous Pseudoangiomatous Stromal Hyperplasia of the Breasts and
      Axillae: Imaging Findings with Pathological and Clinical Correlation.
AB  - Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a pathology that is
      usually diagnosed by accident during pathological examination of other breast
      lesions. PASH is an uncommon and benign tumoral lesion of the mammary stroma that
      can be pathologically mistaken for other tumours, such as phyllodes,
      fibroadenoma, and sometimes even angiosarcoma. We report the case of a 45-year
      old woman with complaints of huge bilateral breast enlargement. This is a rare
      case of PASH presenting with gigantomastia and involving bilateral breasts and
      axillae simultaneously. Mammography, ultrasonography, and MRI features are
      illustrated with histopathological correlation.

PMID- 27867678
TI  - Reduced Dental Plaque Formation in Dogs Drinking a Solution Containing Natural
      Antimicrobial Herbal Enzymes and Organic Matcha Green Tea.
AB  - The results of an exploratory, multicenter clinical study confirmed the
      hypothesis that a novel, natural, and safe oral care product (OCP) reduced the
      rate of plaque formation on teeth of dogs consuming the OCP (antimicrobial plant
      derived enzymes, organic matcha green tea, cultured dextrose, sodium bicarbonate,
      and ascorbic acid) compared to controls. Healthy dogs without periodontitis, of
      varying breeds, sex, and age, were recruited and enrolled, using nonrandomized
      stratification methods, into a control and treatment groups. Treatment group dogs
      drank only water into which OCP was suspended, for 28 days. Control group dogs
      drank their normal household water. On day 0 all teeth were cleaned by a
      veterinarian and gingivitis was assessed. On days 14, 21, and 28 plaque index,
      plaque thickness, gingivitis, freshness of breath, and general health were
      assessed. Over the 28 days of study, dogs on the OCP had significant reduction in
      plaque index and plaque thickness compared to controls. By day 14 OCP reduced
      plaque formation by 37%; the 28-day reduction in plaque index and coverage
      averaged 22% with no measurable gingivitis or calculus. Conclusion. Using the OCP
      attenuated dental plaque formation when consumed as normal drinking water and in
      the absence of other modes of oral care.

PMID- 27867680
TI  - Bilirubin in coronary artery disease: Cytotoxic or protective?
AB  - Bilirubin has traditionally been considered a cytotoxic waste product. However,
      recent studies have shown bilirubin to have anti-oxidant, anti-inflammatory,
      vasodilatory, anti-apoptotic and anti-proliferative functions. These properties
      potentially confer bilirubin a new role of protection especially in coronary
      artery disease (CAD), which is a low grade inflammatory process exacerbated by
      oxidative stress. In fact, recent literature reports an inverse relationship
      between serum concentration of bilirubin and the presence of CAD. In this
      article, we review the current literature exploring the association between
      levels of bilirubin and risk of CAD. We conclude that current evidence is
      inconclusive regarding the protective effect of bilirubin on CAD. A causal
      relationship between low serum bilirubin level and increased risk of CAD is not
      currently established.

PMID- 27867679
TI  - Identification of two novel mutations in the GALNT3 gene in a Chinese family with
      hyperphosphatemic familial tumoral calcinosis.
AB  - Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare, autosomal
      recessive genetic disease. This disease is characterized by the progressive
      calcification of soft tissues leading to symptoms of pressure and
      hyperphosphatemia but normal concentrations of serum calcium with or without an
      elevation of 1,25-dihydroxyvitamin D3 levels.HFTC is caused by loss-of-function
      mutations in the GALNT3, FGF23 or KL genes. Here, we identified two novel
      mutations in the GALNT3 gene in a Chinese family with HFTC. Identification of a
      novel genotype in HFTC provides clues for understanding the phenotype-genotype
      relationships in HFTC and may assist not only in the clinical diagnosis of HFTC
      but also in the interpretation of the genetic information used for prenatal
      diagnosis and genetic counseling.

PMID- 27867681
TI  - Local ablative treatments for hepatocellular carcinoma: An updated review.
AB  - Ablative treatments currently represent the first-line option for the treatment
      of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are
      effective as bridging/downstaging therapies before orthotopic liver
      transplantation. Contraindications based on size, number, and location of nodules
      are quite variable in literature and strictly dependent on local expertise. Among
      ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due
      to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety.
      Although survival outcomes are similar to percutaneous ethanol injection, the
      lower local recurrence rate stands for a wider application of RFA in hepato
      oncology. Moreover, RFA seems to be even more cost-effective than liver resection
      for very early HCC (single nodule <= 2 cm) and in the presence of two or three
      nodules <= 3 cm. There is increasing evidence that combining RFA to transarterial
      chemoembolization may increase the therapeutic benefit in larger HCCs without
      increasing the major complication rate, but more robust prospective data is still
      needed to validate these pivotal findings. Among other thermal treatments,
      microwave ablation (MWA) uses high frequency electromagnetic energy to induce
      tissue death via coagulation necrosis. In comparison to RFA, MWA has several
      theoretical advantages such as a broader zone of active heating, higher
      temperatures within the targeted area in a shorter treatment time and the lack of
      heat-sink effect. The safety concerns raised on the risks of this procedure, due
      to the broader and less predictable necrosis areas, have been recently overcome.
      However, whether MWA ability to generate a larger ablation zone will translate
      into a survival gain remains unknown. Other treatments, such as high-intensity
      focused ultrasound ablation, laser ablation, and cryoablation, are less
      investigated but showed promising results in early HCC patients and could be a
      valuable therapeutic option in the next future.

PMID- 27867683
TI  - Logical hypothesis: Low FODMAP diet to prevent diverticulitis.
AB  - Despite little evidence for the therapeutic benefits of a high-fiber diet for
      diverticulitis, it is commonly recommended as part of the clinical management.
      The ongoing uncertainty of the cause(s) of diverticulitis confounds attempts to
      determine the validity of this therapy. However, the features of a high-fiber
      diet represent a logical contradiction for colon diverticulitis. Considering that
      Bernoulli's principle, by which enlarged diameter of the lumen leads to increased
      pressure and decreased fluid velocity, might contribute to development of the
      diverticulum. Thus, theoretically, prevention of high pressure in the colon would
      be important and adoption of a low FODMAP diet (consisting of fermentable
      oligosaccharides, disaccharides, monosaccharides, and polyols) may help prevent
      recurrence of diverticulitis.

PMID- 27867682
TI  - Treatment of pregnant women with a diagnosis of inflammatory bowel disease.
AB  - The frequency of diagnosis of inflammatory bowel disease (IBD) has increased in
      younger populations. For this reason, pregnancy in patients with IBD is a topic
      of interest, warranting additional focus on disease management during this
      period. The main objective of this article is to summarize the latest findings
      and guidelines on the management of potential problems from pregnancy to the
      breastfeeding stage. Fertility is decreased in patients with active IBD. Disease
      remission prior to conception will likely decrease the rate of pregnancy-related
      complications. Most of the drugs used for IBD treatment are safe during both
      pregnancy and breastfeeding. Two exceptions are methotrexate and thalidomide,
      which are contraindicated in pregnancy. Anti-tumor necrosis factor agents are not
      advised during the third trimester as they exhibit increased transplacental
      transmission and potentially cause immunosuppression in the fetus. Radiological
      and endoscopic examinations and surgical interventions should be performed only
      when absolutely necessary. Surgery increases the fetal mortality rate. The
      delivery method should be determined with consideration of the disease site and
      presence of progression or flare up. Treatment planning should be a collaborative
      effort among the gastroenterologist, obstetrician, colorectal surgeon and
      patient.

PMID- 27867685
TI  - How I treat my inflammatory bowel disease-patients with thiopurines?
AB  - Thiopurines are essential drugs to maintain remission in patients with
      inflammatory bowel disease (IBD). Thiopurines used in IBD are azathioprine (2.0
      2.5 mg/kg), mercaptopurine (1.0-1.5 mg/kg) and thioguanine (0.2-0.3 mg/kg).
      However, mainly due to numerous adverse events associated with thiopurine use,
      almost 50% of the patients have to discontinue conventional thiopurine treatment.
      Extensive monitoring and the application of several treatment strategies, such as
      split-dose administration, co-administration with allopurinol or dose
      reduction/increase, may increase the chance of successful therapy. With this
      review, we provide practical information on how thiopurines are initiated and
      maintained in two thiopurine research centers in The Netherlands. We provide
      clinical information concerning safety issues, indications and management of
      therapy that may serve as a guide for the administration of thiopurines in IBD
      patients in daily practice.

PMID- 27867684
TI  - Eosinophilic gastroenteritis: Approach to diagnosis and management.
AB  - Eosinophilic gastroenteritis (EGE) is a rare and benign inflammatory disorder
      that predominantly affects the stomach and the small intestine. The disease is
      divided into three subtypes (mucosal, muscular and serosal) according to klein's
      classification, and its manifestations are protean, depending on the involved
      intestinal segments and layers. Hence, accurate diagnosis of EGE poses a
      significant challenge to clinicians, with evidence of the following three
      criteria required: Suspicious clinical symptoms, histologic evidence of
      eosinophilic infiltration in the bowel and exclusion of other pathologies with
      similar findings. In this review, we designed and applied an algorithm to clarify
      the steps to follow for diagnosis of EGE in clinical practice. The management of
      EGE represents another area of debate. Prednisone remains the mainstay of
      treatment; however the disease is recognized as a chronic disorder and one that
      most frequently follows a relapsing course that requires maintenance therapy.
      Since prolonged steroid treatment carries of risk of serious adverse effects,
      other options with better safety profiles have been proposed; these include
      budesonide, dietary restrictions and steroid-sparing agents, such as leukotriene
      inhibitors, azathioprine, anti-histamines and mast-cell stabilizers. Single cases
      or small case series have been reported in the literature for all of these
      options, and we provide in this review a summary of these various therapeutic
      modalities, placing them within the context of our novel algorithm for EGE
      management according to disease severity upon presentation.

PMID- 27867686
TI  - Widespread use of gastric acid inhibitors in infants: Are they needed? Are they
      safe?
AB  - Gastroesophageal reflux is a common phenomenon in infants, but the
      differentiation between gastroesophageal reflux and gastroesophageal reflux
      disease can be difficult. Symptoms are non-specific and there is increasing
      evidence that the majority of symptoms may not be acid-related. Despite this,
      gastric acid inhibitors such as proton pump inhibitors are widely and
      increasingly used, often without objective evidence or investigations to guide
      treatment. Several studies have shown that these medications are ineffective at
      treating symptoms associated with reflux in the absence of endoscopically proven
      oesophagitis. With a lack of evidence for efficacy, attention is now being turned
      to the potential risks of gastric acid suppression. Previously assumed safety of
      these medications is being challenged with evidence of potential side effects
      including GI and respiratory infections, bacterial overgrowth, adverse bone
      health, food allergy and drug interactions.

PMID- 27867688
TI  - Usefulness of vonoprazan, a potassium ion-competitive acid blocker, for primary
      eradication of Helicobacter pylori.
AB  - AIM: To investigate usefulness of triple therapy with vonoprazan, a potassium ion
      competitive acid blocker and antibiotics, for Helicobacter pylori (H. pylori)
      eradication. METHODS: The H. pylori eradication rate was examined in 2507
      patients (2055 undergoing primary eradication and 452 undergoing secondary
      eradication, excluding patients with subtotal gastrectomy) at the Japanese Red
      Cross Kyoto Daiichi Hospital from March 2013 to September 2015. For patients
      treated from March 2013 to February 2015, a proton pump inhibitor (PPI) was used
      to reduce acid secretion, while vonoprazan was used after March 2015. The success
      rates of the 2 regimens (PPI + amoxicillin + clarithromycin/metronidazole, or
      vonoprazan + amoxicillin + clarithromycin/metronidazole) were compared. RESULTS:
      The success rate of primary H. pylori eradication was significantly higher in the
      vonoprazan group. When stratified by the underlying disease, a significant
      increase of the H. pylori eradication rate was observed in patients with chronic
      gastritis. A significantly lower H. pylori eradication rate was observed in
      younger patients compared to older patients in the PPI group, but there was no
      difference according to age in the vonoprazan group. On the other hand, the
      success rate of secondary eradication was similar at approximately 90% in both
      groups. CONCLUSION: Vonoprazan is very useful for primary eradication of H.
      pylori, and may become a first-line acid secretion inhibitor instead of PPIs.

PMID- 27867687
TI  - A20 inhibits lipopolysaccharide-induced inflammation in enterocytes.
AB  - AIM: To examine the role of A20 in the regulation of intestinal epithelial cells
      (IECs) inflammation. METHODS: Using gene transfection, both stable overexpression
      and knockdown A20-expressed HT-29 cell lines were established. Accordingly, the
      cells were divided into the following groups: The control group, the A20
      overexpression group, the A20 knockdown group and the respective controls. A20
      was stimulated with lipopolysaccharide (LPS) in a dose- and time-dependent manner
      and was detected using western blotting and real-time polymerase chain reaction
      (PCR) analyses. Immunofluorescence and western blotting analyses were performed
      to investigate the role of A20 in the regulation of nuclear factor (NF)-kappaB
      activation and translocation into the nucleus. ELISA and real-time PCR were
      performed to examine A20 in regulating the release of the following inflammatory
      cytokines: Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL
      8. RESULTS: The expression of A20 in IECs was inducible. When intestinal
      epithelial cells were subjected to the stimulation of LPS, the expression of A20
      was increased, and the expression of A20 was induced in a dose- and time
      dependent manner. The expression of A20 was very low in HT-29 cells without LPS
      stimulation but rapidly increased and was maintained at a high level 2-4 h after
      stimulation with LPS. These levels gradually declined with a change in time
      course, and the expression of A20 increased with increasing LPS stimulation.
      Western blotting and immunofluorescence revealed that overexpression of A20 can
      inhibit NF-kappaB activation and its translocation to the nucleus. The
      overexpression of A20 can reduce the levels of proinflammatory cytokines involved
      in the pathophysiology of inflammatory bowel disease. There was no significant
      difference in the expression of IL-8 mRNA in the control group, A20
      overexpression group or A20 knockdown group without LPS stimulation (P > 0.05);
      however, while after 2 h, 4 h and 8 h stimulation with LPS, the expression of IL
      8 in the A20 overexpression group was lower than the control group and the A20
      knockdown group (P < 0.05 or P < 0.01). The expression of TNF-alpha was different
      at different time points after 8 h of LPS stimulation (F = 31.33, DF = 5, P <
      0.001), and the expression of TNF-alpha increased as the LPS stimulation time
      increased. Upon LPS stimulation, lower levels of TNF-alpha were detected in the
      A20 overexpression cell lines (P < 0.05). There were no significant differences
      in the induction of IL-6 and IL-1beta among the control group, A20 overexpression
      group and A20 knockdown group (P > 0.05). CONCLUSION: A20 plays an important role
      in limiting inflammation by inhibiting LPS-induced NF-kappaB responses in the gut
      luminal. A20 may be a potential therapeutic tool for inflammatory diseases.

PMID- 27867689
TI  - Family history and disease outcomes in patients with Crohn's disease: A
      comparison between China and the United States.
AB  - AIM: To investigate the differences in family history of inflammatory bowel
      disease (IBD) and clinical outcomes among individuals with Crohn's disease (CD)
      residing in China and the United States. METHODS: We performed a survey-based
      cross-sectional study of participants with CD recruited from China and the United
      States. We compared the prevalence of IBD family history and history of ileal
      involvement, CD-related surgeries and IBD medications in China and the United
      States, adjusting for potential confounders. RESULTS: We recruited 49
      participants from China and 145 from the United States. The prevalence of family
      history of IBD was significantly lower in China compared with the United States
      (China: 4.1%, United States: 39.3%). The three most commonly affected types of
      relatives were cousin, sibling, and parent in the United States compared with
      child and sibling in China. Ileal involvement (China: 63.3%, United States:
      63.5%) and surgery for CD (China: 51.0%, United States: 49.7%) were nearly
      equivalent in the two countries. CONCLUSION: The lower prevalence of familial
      clustering of IBD in China may suggest that the etiology of CD is less attributed
      to genetic background or a family-shared environment compared with the United
      States. Despite the potential difference in etiology, surgery and ileal
      involvement were similar in the two countries. Examining the changes in family
      history during the continuing rise in IBD may provide further insight into the
      etiology of CD.

PMID- 27867690
TI  - Good adherence to mediterranean diet can prevent gastrointestinal symptoms: A
      survey from Southern Italy.
AB  - AIM: To evaluate how different levels of adherence to a mediterranean diet (MD)
      correlate with the onset of functional gastrointestinal disorders. METHODS: As
      many as 1134 subjects (598 M and 536 F; age range 17-83 years) were prospectively
      investigated in relation to their dietary habits and the presence of functional
      gastrointestinal symptoms. Patients with relevant chronic organic disease were
      excluded from the study. The Mediterranean Diet Quality index for children and
      adolescents (KIDMED) and the Short Mediterranean Diet Questionnaire were
      administered. All subjects were grouped into five categories according to their
      ages: 17-24 years; 25-34; 35-49; 50-64; above 64. RESULTS: On the basis of the
      Rome III criteria, our population consisted of 719 (63.4%) individuals who did
      not meet the criteria for any functional disorder and were classified as controls
      (CNT), 172 (13.3%) patients meeting criteria for prevalent irritable bowel
      syndrome (IBS), and 243 (23.3%) meeting criteria for prevalent functional
      dyspepsia (FD). A significantly lower adherence score in IBS (0.57 +/- 0.23, P <
      0.001) and FD (0.56 +/- 0.24, P < 0.05) was found compared to CNT (0.62 +/-
      0.21). Females with FD and IBS exhibited significantly lower adherence scores
      (respectively 0.58 +/- 0.24, P < 0.05 and 0.56 +/- 0.22, P < 0.05) whereas males
      were significantly lower only for FD (0.53 +/- 0.25, P < 0.05). Age cluster
      analyses showed a significantly lower score in the 17-24 years and 25-34 year
      categories for FD (17-24 years: 0.44 +/- 0.21, P < 0.001; 25-34 years: 0.48 +/-
      0.22, P < 0.05) and IBS (17-24 years: 0.45 +/- 0.20, P < 0.05; 24-34 years: 0.44
      +/- 0.21, P < 0.001) compared to CNT (17-24 years: 0.56 +/- 0.21; 25-34 years:
      0.69 +/- 0.20). CONCLUSION: Low adherence to MD may trigger functional
      gastrointestinal symptoms, mainly in younger subjects. Moreover, with increasing
      age, patients tend to adopt dietary regimens closer to MD.

PMID- 27867691
TI  - Efficacy of small-volume simethicone given at least 30 min before gastroscopy.
AB  - AIM: To evaluate the efficacy of 5 mL simethicone solution in decreasing gastric
      foam if given at least 30 min before gastroscopy. METHODS: This was a randomized,
      placebo controlled, endoscopist blinded study performed at Changi General
      Hospital. Patients were at least 21 years old, had no prior surgical resection of
      the upper gastrointestinal tract, and scheduled for elective diagnostic
      gastroscopies. The primary outcome was the total mucosal visibility score (TMVS)
      which was evaluated using McNally score. The sample size was calculated to be 24
      per group (SD 2.4, 80% power, P < 0.05, 2-sample t test). RESULTS: Fifty-four
      patients were randomised to receive either simethicone [1 mL liquid simethicone
      (100 mg) in 5 mL of water] or placebo (5 mL of water) at least 30 min before
      their gastroscopy. Six accredited consultants conducted the gastroscopy, and the
      interobserver agreement of scoring TMVS was good with a Kappa statistic of 0.73.
      The simethicone group had significantly better mean TMVS compared to placebo
      (5.78 +/- SD 1.65 vs 8.89 +/- SD 1.97, P < 0.001). The improvement was
      statistically significant for the duodenum and the gastric antrum, angularis,
      body, and fundus. Percent 51.9 of patients in the simethicone group had a TMVS of
      4 (no bubbles at all) to 5 (only 1 area with minimal bubbles), while in the
      placebo group 3.7% of patients had TMVS of 4 or 5. The number needed to treat was
      2.1 to avoid a TMVS of 6 and more. The simethicone group also had a significantly
      shorter procedure time with less volume of additional flushes required during
      gastroscopy to clear away obscuring gastric foam. CONCLUSION: With a
      premedication time of at least 30 min, 5 mL simethicone can significantly
      decrease gastric foam, decrease the volume of additional flushes, and shorten
      gastroscopy time.

PMID- 27867692
TI  - Osteonecrosis of both knees in a woman with Crohn's disease.
AB  - Osteonecrosis is a very rare complication of Crohn's disease (CD). It is not
      clear if it is related to corticosteroid therapy or if it occurs as an
      extraintestinal manifestation of inflammatory bowel disease. We present the case
      of a patient with CD who presented with osteonecrosis of both knees. A 22 years
      old woman was diagnosed with CD in April 2012 (Montreal Classification A2L1 +
      L4B3p). She was started on prednisolone (40 mg/d), azathioprine (100 mg/d) and
      messalazine (3 g/d). In July 2012, due to active perianal disease, infliximab
      therapy was initiated. In September 2012, she had a pelvic abscess complicated by
      peritonitis and an ileal segmental resection and right hemicolectomy were
      performed. In December 2012 she was diagnosed with bilateral septic arthritis of
      both knees with walking impairment. She was treated with amoxicillin-clavulanic
      acid, started a physical rehabilitation program and progressively improved.
      However, then, bilateral knee pain exacerbated by movement developed. Magnetic
      resonance imaging showed multiple osseous medullary infarcts in the distal
      extremity of the femurs, proximal extremity of the tibiae and patellas and no
      signs of subchondral collapse, which is consistent with osteonecrosis. The
      patient recovered completely and maintains therapy with azathioprine and
      messalazine. A review of the literature is also done.

PMID- 27867693
TI  - Gastroenterology, hepatology and movies: A holistic insight.
AB  - The Project "Movies and Health in Night talks" took place in Braga and Porto,
      northern Portugal, in the last 3 years. This Project demonstrated how medical
      knowledge may surround and integrate a cosmopolitan and holistic approach, so
      that we as doctors and the general public, are able to become much closer and
      much more prone to understand the vital cycles of our society.

PMID- 27867694
TI  - TakeCARE, a Video Bystander Program to Help Prevent Sexual Violence on College
      Campuses: Results of Two Randomized, Controlled Trials.
AB  - OBJECTIVE: The present research reports on two randomized controlled trials
      evaluating TakeCARE, a video bystander program designed to help prevent sexual
      violence on college campuses. METHOD: In Study 1, students were recruited from
      psychology courses at two universities. In Study 2, first-year students were
      recruited from a required course at one university. In both studies, students
      were randomly assigned to view one of two videos: TakeCARE or a control video on
      study skills. Just before viewing the videos, students completed measures of
      bystander behavior toward friends and ratings of self-efficacy for performing
      such behaviors. The efficacy measure was administered again after the video, and
      both the bystander behavior measure and the efficacy measure were administered at
      either one (Study 1) or two (Study 2) months later. RESULTS: In both studies,
      students who viewed TakeCARE, compared to students who viewed the control video,
      reported engaging in more bystander behavior toward friends and greater feelings
      of efficacy for performing such behavior. In Study 1, feelings of efficacy
      mediated effects of TakeCARE on bystander behavior; this result did not emerge in
      Study 2. CONCLUSIONS: This research demonstrates that TakeCARE, a video bystander
      program, can positively influence bystander behavior toward friends. Given its
      potential to be easily distributed to an entire campus community, TakeCARE might
      be an effective addition to campus efforts to prevent sexual violence.

PMID- 27867695
TI  - Quantitative photoacoustic image reconstruction improves accuracy in deep tissue
      structures.
AB  - Photoacoustic imaging (PAI) is emerging as a potentially powerful imaging tool
      with multiple applications. Image reconstruction for PAI has been relatively
      limited because of limited or no modeling of light delivery to deep tissues. This
      work demonstrates a numerical approach to quantitative photoacoustic image
      reconstruction that minimizes depth and spectrally derived artifacts. We present
      the first time-domain quantitative photoacoustic image reconstruction algorithm
      that models optical sources through acoustic data to create quantitative images
      of absorption coefficients. We demonstrate quantitative accuracy of less than 5%
      error in large 3 cm diameter 2D geometries with multiple targets and within 22%
      error in the largest size quantitative photoacoustic studies to date (6cm
      diameter). We extend the algorithm to spectral data, reconstructing 6 varying
      chromophores to within 17% of the true values. This quantitiative PA tomography
      method was able to improve considerably on filtered-back projection from the
      standpoint of image quality, absolute, and relative quantification in all our
      simulation geometries. We characterize the effects of time step size, initial
      guess, and source configuration on final accuracy. This work could help to
      generate accurate quantitative images from both endogenous absorbers and
      exogenous photoacoustic dyes in both preclinical and clinical work, thereby
      increasing the information content obtained especially from deep-tissue
      photoacoustic imaging studies.

PMID- 27867696
TI  - Quantification of extra-cerebral and cerebral hemoglobin concentrations during
      physical exercise using time-domain near infrared spectroscopy.
AB  - Fitness is known to have beneficial effects on brain anatomy and function.
      However, the understanding of mechanisms underlying immediate and long-term
      neurophysiological changes due to exercise is currently incomplete due to the
      lack of tools to investigate brain function during physical activity. In this
      study, we used time-domain near infrared spectroscopy (TD-NIRS) to quantify and
      discriminate extra-cerebral and cerebral hemoglobin concentrations and oxygen
      saturation (SO2) in young adults at rest and during incremental intensity
      exercise. In extra-cerebral tissue, an increase in deoxy-hemoglobin (HbR) and a
      decrease in SO2 were observed while only cerebral HbR increased at high intensity
      exercise. Results in extra-cerebral tissue are consistent with thermoregulatory
      mechanisms to dissipate excess heat through skin blood flow, while cerebral
      changes are in agreement with cerebral blood flow (CBF) redistribution mechanisms
      to meet oxygen demand in activated regions during exercise. No significant
      difference was observed in oxy- (HbO2) and total hemoglobin (HbT). In addition
      HbO2, HbR and HbT increased with subject's peak power output (equivalent to the
      maximum oxygen volume consumption; VO2 peak) supporting previous observations of
      increased total mass of red blood cells in trained individuals. Our results also
      revealed known gender differences with higher hemoglobin in men. Our approach in
      quantifying both extra-cerebral and cerebral absolute hemoglobin during exercise
      may help to better interpret past and future continuous-wave NIRS studies that
      are prone to extra-cerebral contamination and allow a better understanding of
      acute cerebral changes due to physical exercise.

PMID- 27867698
TI  - Mapping 3D fiber orientation in tissue using dual-angle optical polarization
      tractography.
AB  - Optical polarization tractography (OPT) has recently been applied to map fiber
      organization in the heart, skeletal muscle, and arterial vessel wall with high
      resolution. The fiber orientation measured in OPT represents the 2D projected
      fiber angle in a plane that is perpendicular to the incident light. We report
      here a dual-angle extension of the OPT technology to measure the actual 3D fiber
      orientation in tissue. This method was first verified by imaging the murine
      extensor digitorum muscle placed at various known orientations in space. The
      accuracy of the method was further studied by analyzing the 3D fiber orientation
      of the mouse tibialis anterior muscle. Finally we showed that dual-angle OPT
      successfully revealed the unique 3D "arcade" fiber structure in the bovine
      articular cartilage.

PMID- 27867697
TI  - Joint blood flow is more sensitive to inflammatory arthritis than oxyhemoglobin,
      deoxyhemoglobin, and oxygen saturation.
AB  - Joint hypoxia plays a central role in the progression and perpetuation of
      rheumatoid arthritis (RA). Thus, optical techniques that can measure surrogate
      markers of hypoxia such as blood flow, oxyhemoglobin, deoxyhemoglobin, and oxygen
      saturation are being developed to monitor RA. The purpose of the current study
      was to compare the sensitivity of these physiological parameters to arthritis.
      Experiments were conducted in a rabbit model of RA and the results revealed that
      joint blood flow was the most sensitive to arthritis and could detect a
      statistically significant difference (p<0.05, power = 0.8) between inflamed and
      healthy joints with a sample size of only four subjects. Considering that this a
      quantitative technique, the high sensitivity to arthritis suggests that joint
      perfusion has the potential to become a potent tool for monitoring disease
      progression and treatment response in RA.

PMID- 27867699
TI  - Characterization of autism spectrum disorder with spontaneous hemodynamic
      activity.
AB  - Functional near-infrared spectroscopy (fNIRS) was used to investigate spontaneous
      hemodynamic activity in the temporal cortex for typically developing (TD)
      children and children with autism spectrum disorder (ASD). Forty-seven children
      participated in the experiments including twenty-five with ASD. Compared with TD
      children, children with ASD showed weaker bilateral resting-state functional
      connectivity (RSFC), but much stronger fluctuation magnitude in terms of oxy
      hemoglobin (HbO2) and deoxy-hemoglobin (Hb). Differentiating between ASD and TD
      based on a support vector machine (SVM) model including bilateral RSFC and the
      fluctuation power of HbO2 and Hb as variables could achieve high accurate
      classification with sensitivity of 81.6% and specificity of 94.6%. This study
      demonstrates optical brain imaging has the potential for screening children with
      risk of ASD.

PMID- 27867700
TI  - Mental stress assessment using simultaneous measurement of EEG and fNIRS.
AB  - Previous studies reported mental stress as one of the major contributing factors
      leading to various diseases such as heart attack, depression and stroke. An
      accurate stress assessment method may thus be of importance to clinical
      intervention and disease prevention. We propose a joint independent component
      analysis (jICA) based approach to fuse simultaneous measurement of
      electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) on
      the prefrontal cortex (PFC) as a means of stress assessment. For the purpose of
      this study, stress was induced by using an established mental arithmetic task
      under time pressure with negative feedback. The induction of mental stress was
      confirmed by salivary alpha amylase test. Experiment results showed that the
      proposed fusion of EEG and fNIRS measurements improves the classification
      accuracy of mental stress by +3.4% compared to EEG alone and +11% compared to
      fNIRS alone. Similar improvements were also observed in sensitivity and
      specificity of proposed approach over unimodal EEG/fNIRS. Our study suggests that
      combination of EEG (frontal alpha rhythm) and fNIRS (concentration change of
      oxygenated hemoglobin) could be a potential means to assess mental stress
      objectively.

PMID- 27867701
TI  - Real-time photo-magnetic imaging.
AB  - We previously introduced a new high resolution diffuse optical imaging modality
      termed, photo-magnetic imaging (PMI). PMI irradiates the object under
      investigation with near-infrared light and monitors the variations of temperature
      using magnetic resonance thermometry (MRT). In this paper, we present a real-time
      PMI image reconstruction algorithm that uses analytic methods to solve the
      forward problem and assemble the Jacobian matrix much faster. The new algorithm
      is validated using real MRT measured temperature maps. In fact, it accelerates
      the reconstruction process by more than 250 times compared to a single iteration
      of the FEM-based algorithm, which opens the possibility for the real-time PMI.

PMID- 27867703
TI  - Deep imaging of absorption and scattering features by multispectral multiple
      scattering low coherence interferometry.
AB  - We have developed frequency domain multispectral multiple scattering low
      coherence interferometry (ms2/LCI) for deep imaging of absorption and scattering
      contrast. Using tissue-mimicking phantoms that match the full scattering phase
      function of human dermal tissue, we demonstrate that ms2/LCI can provide a
      signal/noise ratio (SNR) improvement of 15.4 dB over conventional OCT at an
      imaging depth of 1 mm. The enhanced SNR and penetration depth provided by ms2/LCI
      could be leveraged for a variety of clinical applications including the
      assessment of burn injuries where current clinical classification of severity
      only provides limited accuracy. The utility of the approach was demonstrated by
      imaging a tissue phantom simulating a partial-thickness burn revealing good
      spectroscopic contrast between healthy and injured tissue regions deep below the
      sample surface. Finally, healthy rat skin was imaged in vivo with both a
      commercial OCT instrument and our custom ms2/LCI system. The results demonstrate
      that ms2/LCI is capable of obtaining spectroscopic information far beyond the
      penetration depth provided by conventional OCT.

PMID- 27867702
TI  - Evaluation of artifact reduction in optical coherence tomography angiography with
      real-time tracking and motion correction technology.
AB  - Artifacts introduced by eye motion in optical coherence tomography angiography
      (OCTA) affect the interpretation of images and the quantification of parameters
      with clinical value. Eradication of such artifacts in OCTA remains a technical
      challenge. We developed an algorithm that recognizes five different types of
      motion artifacts and used it to evaluate the performance of three motion removal
      technologies. On en face maximum projection of flow images, the summed flow
      signal in each row and column and the correlation between neighboring rows and
      columns were calculated. Bright line artifacts were recognized by large summed
      flow signal. Drifts, distorted lines, and stretch artifacts exhibited abnormal
      correlation values. Residual lines were simultaneously a local maximum of summed
      flow and a local minimum of correlation. Tracking-assisted scanning integrated
      with motion correction technology (MCT) demonstrated higher performance than
      tracking or MCT alone in healthy and diabetic eyes.

PMID- 27867704
TI  - Quantitative chemical imaging with background-free multiplex coherent anti-Stokes
      Raman scattering by dual-soliton Stokes pulses.
AB  - Coherent anti-Stokes Raman microscopy (CARS) is a quantitative, chemically
      specific, and label-free optical imaging technique for studying inhomogeneous
      systems. However, the complicating influence of the nonresonant response on the
      CARS signal severely limits its sensitivity and specificity and especially limits
      the extent to which CARS microscopy has been used as a fully quantitative imaging
      technique. On the basis of spectral focusing mechanism, we establish a dual
      soliton Stokes based CARS microspectroscopy and microscopy scheme capable of
      quantifying the spatial information of densities and chemical composition within
      inhomogeneous samples, using a single fiber laser. Dual-soliton Stokes scheme not
      only removes the nonresonant background but also allows robust acquisition of
      multiple characteristic vibrational frequencies. This all-fiber based laser
      source can cover the entire fingerprint (800-2200 cm-1) region with a spectral
      resolution of 15 cm-1. We demonstrate that quantitative degree determination of
      lipid-chain unsaturation in the fatty acids mixture can be achieved by the
      characterization of C = C stretching and CH2 deformation vibrations. For
      microscopy purposes, we show that the spatially inhomogeneous distribution of
      lipid droplets can be further quantitatively visualized using this quantified
      degree of lipid unsaturation in the acyl chain for contrast in the hyperspectral
      CARS images. The combination of compact excitation source and background-free
      capability to facilitate extraction of quantitative composition information with
      multiplex spectral peaks will enable wider applications of quantitative chemical
      imaging in studying biological and material systems.

PMID- 27867706
TI  - Simultaneous in vivo imaging of diffuse optical reflectance, optoacoustic
      pressure and ultrasonic scattering.
AB  - We present reflection-mode bioimaging system providing complementary optical,
      photoacsoutic and acoustic measurements by acoustic detector after each laser
      pulse. While the photons absorbed within the sample provide optoacoustic (OA)
      signals, the photons absorbed by the external electrode of a detector provide the
      measurable diffuse reflectance (DR) from the sample and the probing ultrasonic
      (US) pulse. To demonstrate the in vivo capabilities of the system we present the
      results of complementary DR/OA/US imaging of a mouse tumor, head of a newborn
      rat, and the back of a newborn rat with 3.5mm/50MUm/35MUm lateral resolution.
      Trimodal approach allows visualization of mechanical structures in healthy and
      pathological tissues along with peculiarities of blood supply. The system may be
      used for diagnostics of diseases accompanied by the defects of vascularization as
      well as for assessing the mechanisms of vascular changes when monitoring response
      to therapy.

PMID- 27867705
TI  - 3D differential phase contrast microscopy.
AB  - We demonstrate 3D phase and absorption recovery from partially coherent intensity
      images captured with a programmable LED array source. Images are captured through
      focus with four different illumination patterns. Using first Born and weak object
      approximations (WOA), a linear 3D differential phase contrast (DPC) model is
      derived. The partially coherent transfer functions relate the sample's complex
      refractive index distribution to intensity measurements at varying defocus.
      Volumetric reconstruction is achieved by a global FFT-based method, without an
      intermediate 2D phase retrieval step. Because the illumination is spatially
      partially coherent, the transverse resolution of the reconstructed field achieves
      twice the NA of coherent systems and improved axial resolution.

PMID- 27867707
TI  - Scanless functional imaging of hippocampal networks using patterned two-photon
      illumination through GRIN lenses.
AB  - Patterned illumination through the phase modulation of light is increasingly
      recognized as a powerful tool to investigate biological tissues in combination
      with two-photon excitation and light-sensitive molecules. However, to date two
      photon patterned illumination has only been coupled to traditional microscope
      objectives, thus limiting the applicability of these methods to superficial
      biological structures. Here, we show that phase modulation can be used to
      efficiently project complex two-photon light patterns, including arrays of points
      and large shapes, in the focal plane of graded index (GRIN) lenses. Moreover,
      using this approach in combination with the genetically encoded calcium indicator
      GCaMP6, we validate our system performing scanless functional imaging in rodent
      hippocampal networks in vivo ~1.2 mm below the brain surface. Our results open
      the way to the application of patterned illumination approaches to deep regions
      of highly scattering biological tissues, such as the mammalian brain.

PMID- 27867709
TI  - Optimal wavelengths for optoacoustic measurements of blood oxygen saturation in
      biological tissues.
AB  - The non-invasive measurement of blood oxygen saturation in blood vessels is a
      promising clinical application of optoacoustic imaging. Nevertheless, precise
      optoacoustic measurements of blood oxygen saturation are limited because of the
      complexities of calculating the spatial distribution of the optical fluence. In
      the paper error in the determination of blood oxygen saturation, associated with
      the use of approximate methods of optical fluence evaluation within the blood
      vessel, was investigated for optoacoustic measurements at two wavelengths. The
      method takes into account both acoustic pressure noise and the error in
      determined values of the optical scattering and absorption coefficients used for
      the calculation of the fluence. It is shown that, in conditions of an unknown (or
      partially known) spatial distribution of fluence at depths of 2 to 8 mm, minimal
      error in the determination of blood oxygen saturation is achieved at wavelengths
      of 658 +/- 40 nm and 1069 +/- 40 nm.

PMID- 27867708
TI  - In vivo volumetric fluorescence sectioning microscopy with mechanical-scan-free
      hybrid illumination imaging.
AB  - Optical sectioning microscopy in wide-field fashion has been widely used to
      obtain three-dimensional images of biological samples; however, it requires
      scanning in depth and considerable time to acquire multiple depth information of
      a volumetric sample. In this paper, in vivo optical sectioning microscopy with
      volumetric hybrid illumination, with no mechanical moving parts, is presented.
      The proposed system is configured such that the optical sectioning is provided by
      hybrid illumination using a digital micro-mirror device (DMD) for uniform and non
      uniform pattern projection, while the depth of imaging planes is varied by using
      an electrically tunable-focus lens with invariant magnification and resolution.
      We present and characterize the design, implementation, and experimentally
      demonstrate the proposed system's ability through 3D imaging of in vivo
      Canenorhabditis elegans' growth cones.

PMID- 27867710
TI  - Intraocular scattering compensation in retinal imaging.
AB  - Intraocular scattering affects fundus imaging in a similar way that affects
      vision; it causes a decrease in contrast which depends on both the intrinsic
      scattering of the eye but also on the dynamic range of the image. Consequently,
      in cases where the absolute intensity in the fundus image is important,
      scattering can lead to a wrong estimation. In this paper, a setup capable of
      acquiring fundus images and estimating objectively intraocular scattering was
      built, and the acquired images were then used for scattering compensation in
      fundus imaging. The method consists of two parts: first, reconstruct the
      individual's wide-angle Point Spread Function (PSF) at a specific wavelength to
      be used within an enhancement algorithm on an acquired fundus image to compensate
      for scattering. As a proof of concept, a single pass measurement with a scatter
      filter was carried out first and the complete algorithm of the PSF reconstruction
      and the scattering compensation was applied. The advantage of the single pass
      test is that one can compare the reconstructed image with the original one and
      see the validity, thus testing the efficiency of the method. Following the test,
      the algorithm was applied in actual fundus images in human eyes and the effect on
      the contrast of the image before and after the compensation was compared. The
      comparison showed that depending on the wavelength, contrast can be reduced by
      8.6% under certain conditions.

PMID- 27867711
TI  - Automated data selection method to improve robustness of diffuse optical
      tomography for breast cancer imaging.
AB  - Imaging-guided near infrared diffuse optical tomography (DOT) has demonstrated a
      great potential as an adjunct modality for differentiation of malignant and
      benign breast lesions and for monitoring treatment response of breast cancers.
      However, diffused light measurements are sensitive to artifacts caused by
      outliers and errors in measurements due to probe-tissue coupling, patient and
      probe motions, and tissue heterogeneity. In general, pre-processing of the
      measurements is needed by experienced users to manually remove these outliers and
      therefore reduce imaging artifacts. An automated method of outlier removal, data
      selection, and filtering for diffuse optical tomography is introduced in this
      manuscript. This method consists of multiple steps to first combine several data
      sets collected from the same patient at contralateral normal breast and form a
      single robust reference data set using statistical tests and linear fitting of
      the measurements. The second step improves the perturbation measurements by
      filtering out outliers from the lesion site measurements using model based
      analysis. The results of 20 malignant and benign cases show similar performance
      between manual data processing and automated processing and improvement in tissue
      characterization of malignant to benign ratio by about 27%.

PMID- 27867712
TI  - Enhancement of image quality and imaging depth with Airy light-sheet microscopy
      in cleared and non-cleared neural tissue.
AB  - We have investigated the effect of Airy illumination on the image quality and
      depth penetration of digitally scanned light-sheet microscopy in turbid neural
      tissue. We used Fourier analysis of images acquired using Gaussian and Airy light
      sheets to assess their respective image quality versus penetration into the
      tissue. We observed a three-fold average improvement in image quality at 50 MUm
      depth with the Airy light-sheet. We also used optical clearing to tune the
      scattering properties of the tissue and found that the improvement when using an
      Airy light-sheet is greater in the presence of stronger sample-induced
      aberrations. Finally, we used homogeneous resolution probes in these tissues to
      quantify absolute depth penetration in cleared samples with each beam type. The
      Airy light-sheet method extended depth penetration by 30% compared to a Gaussian
      light-sheet.

PMID- 27867713
TI  - Wavelength-normalized spectroscopic analysis of Staphylococcus aureus and
      Pseudomonas aeruginosa growth rates.
AB  - Optical density (OD) measurements are the standard approach used in microbiology
      for characterizing bacteria concentrations in culture media. OD is based on
      measuring the optical absorbance of a sample at a single wavelength, and any
      error will propagate through all calculations, leading to reproducibility issues.
      Here, we use the conventional OD technique to measure the growth rates of two
      different species of bacteria, Pseudomonas aeruginosa and Staphylococcus aureus.
      The same samples are also analyzed over the entire UV-Vis wavelength spectrum,
      allowing a distinctly different strategy for data analysis to be performed.
      Specifically, instead of only analyzing a single wavelength, a multi-wavelength
      normalization process is implemented. When the OD method is used, the detected
      signal does not follow the log growth curve. In contrast, the multi-wavelength
      normalization process minimizes the impact of bacteria byproducts and
      environmental noise on the signal, thereby accurately quantifying growth rates
      with high fidelity at low concentrations.

PMID- 27867714
TI  - Automatic identification of the temporal retinal nerve fiber raphe from macular
      cube data.
AB  - We evaluated several approaches for automatic location of the temporal nerve
      fiber raphe from standard macular cubes acquired on a Heidelberg Spectralis OCT.
      Macular cubes with B-scan separation of 96-122 um were acquired from 15 healthy
      participants, and "high density" cubes with scan separation of 11 um were
      acquired from the same eyes. These latter scans were assigned to experienced
      graders for subjective location of the raphe, providing the ground truth by which
      to compare methods operating on the lower density data. A variety of OCT scan
      parameters and image processing strategies were trialed. Vertically oriented
      scans, purposeful misalignment of the pupil to avoid reflective artifacts, and
      the use of intensity as opposed to thickness of the nerve fiber layer were all
      critical to minimize error. The best performing approach "cFan" involved
      projection of a fan of lines from each of several locations across the foveal
      pit; in each fan the line of least average intensity was identified. The centroid
      of the crossing points of these lines provided the raphe orientation with an
      average error of 1.5 degrees  (max = 4.1 degrees ) relative to the human graders.
      The disc-fovea-raphe angle was 172.4 +/- 2.3 degrees  (range = 168.5-176.2
      degrees ), which agrees well with other published estimates.

PMID- 27867715
TI  - Changes of collagen ultrastructure in breast cancer tissue determined by second
      harmonic generation double Stokes-Mueller polarimetric microscopy.
AB  - Second-harmonic generation (SHG) double Stokes-Mueller polarimetric microscopy is
      applied to study the alteration of collagen ultrastructure in a tissue microarray
      containing three pathological human breast cancer types with differently
      overexpressed estrogen receptor (ER), progesterone receptor (PgR), and human
      epidermal growth factor receptor 2 (HER2). Kleinman symmetry is experimentally
      validated in breast tissue for 1028 nm laser wavelength and it has been shown
      that measurements with only linearly polarized incoming and outgoing states can
      determine molecular nonlinear susceptibility tensor component ratio, average in
      plane orientation of collagen fibers and degree of linear polarization of SHG.
      Increase in the susceptibility ratio for ER, PgR, HER2 positive cases, reveals
      ultrastructural changes in the collagen fibers while the susceptibility ratio
      increase and decrease in degree of linear polarization for ER and PgR positive
      cases indicate alteration of the ultrastructure and increased disorder of the
      collagen fibers within each focal volume. The study demonstrates a potential use
      of polarimetric SHG microscopy for collagen characterization and cancer
      diagnostics.

PMID- 27867716
TI  - Automatic classification of atherosclerotic plaques imaged with intravascular
      OCT.
AB  - Intravascular optical coherence tomography (IV-OCT) allows evaluation of
      atherosclerotic plaques; however, plaque characterization is performed by visual
      assessment and requires a trained expert for interpretation of the large data
      sets. Here, we present a novel computational method for automated IV-OCT plaque
      characterization. This method is based on the modeling of each A-line of an IV
      OCT data set as a linear combination of a number of depth profiles. After
      estimating these depth profiles by means of an alternating least square
      optimization strategy, they are automatically classified to predefined tissue
      types based on their morphological characteristics. The performance of our
      proposed method was evaluated with IV-OCT scans of cadaveric human coronary
      arteries and corresponding tissue histopathology. Our results suggest that this
      methodology allows automated identification of fibrotic and lipid-containing
      plaques. Moreover, this novel computational method has the potential to enable
      high throughput atherosclerotic plaque characterization.

PMID- 27867717
TI  - Holographic tomography with scanning of illumination: space-domain reconstruction
      for spatially invariant accuracy.
AB  - The paper presents two novel, space-domain reconstruction algorithms for
      holographic tomography utilizing scanning of illumination and a fixed detector
      that is highly suitable for imaging of living biomedical specimens. The first
      proposed algorithm is an adaptation of the filtered backpropagation to the
      scanning illumination tomography. Its space-domain implementation enables
      avoiding the error-prone interpolation in the Fourier domain, which is a
      significant problem of the state-of-the-art tomographic algorithm. The second
      proposed algorithm is a modified version of the former, which ensures the
      spatially invariant reconstruction accuracy. The utility of the proposed
      algorithms is demonstrated with numerical simulations and experimental
      measurement of a cancer cell.

PMID- 27867719
TI  - Monitoring cerebral oxygenation and local field potential with a variation of
      isoflurane concentration in a rat model.
AB  - We aimed to investigate experimentally how anesthetic levels affect cerebral
      metabolism measured by near-infrared spectroscopy (NIRS) and to identify a robust
      marker among NIRS parameters to discriminate various stages of anesthetic depth
      in rats under isoflurane anesthesia. In order to record the hemodynamic changes
      and local field potential (LFP) in the brain, fiber-optic cannulae and custom
      made microelectrodes were implanted in the frontal cortex of the skull. The NIRS
      and LFP signals were continuously monitored before, during and after isoflurane
      anesthesia. As isoflurane concentration is reduced, the level of oxyhemoglobin
      and total hemoglobin concentrations of the frontal cortex decreased gradually,
      while deoxyhemoglobin increased. The reflectance ratio between 730nm and 850nm
      and burst suppression ratio (BSR) correspond similarly with the change of
      oxyhemoglobin during the variation of isoflurane concentration. These results
      suggest that NIRS signals in addition to EEG may provide a possibility of
      developing a new anesthetic depth index.

PMID- 27867720
TI  - Biodegradable polymeric nanoparticles containing gold nanoparticles and
      Paclitaxel for cancer imaging and drug delivery using photoacoustic methods.
AB  - In this study, optical-triggered multifunctional theranostic agents for
      photoacoustic/fluorescent imaging and cancer therapy have been developed. This
      system consists of a perfluorohexane liquid and gold nanoparticles (GNPs) in the
      core, stabilized by a Poly (lactide-co-glycolic acid) (PLGA) polymer shell. When
      cancer cells containing PLGA-GNPs were exposed to laser pulses, cell viability
      decreased due to the vaporization of the particles in and around the cells. The
      particle chemo drug loading and delivery capacity was also investigated in vitro
      experiments. These particles show potential as photoacoustic imaging and therapy
      agents for future clinical translation in cancer therapy.

PMID- 27867718
TI  - Temporal multiplexing with adaptive optics for simultaneous vision.
AB  - We present and test a methodology for generating simultaneous vision with a
      deformable mirror that changed shape at 50 Hz between two vergences: 0 D (far
      vision) and -2.5 D (near vision). Different bifocal designs, including toric and
      combinations of spherical aberration, were simulated and assessed objectively. We
      found that typical corneal aberrations of a 60-year-old subject changes the shape
      of objective through-focus curves of a perfect bifocal lens. This methodology can
      be used to investigate subjective visual performance for different multifocal
      contact or intraocular lens designs.

PMID- 27867721
TI  - Wide-field optical coherence micro-elastography for intraoperative assessment of
      human breast cancer margins.
AB  - Incomplete excision of malignant tissue is a major issue in breast-conserving
      surgery, with typically 20 - 30% of cases requiring a second surgical procedure
      arising from postoperative detection of an involved margin. We report advances in
      the development of a new intraoperative tool, optical coherence micro
      elastography, for the assessment of tumor margins on the micro-scale. We
      demonstrate an important step by conducting whole specimen imaging in
      intraoperative time frames with a wide-field scanning system acquiring mosaicked
      elastograms with overall dimensions of ~50 * 50 mm, large enough to image an
      entire face of most lumpectomy specimens. This capability is enabled by a wide
      aperture annular actuator with an internal diameter of 65 mm. We demonstrate
      feasibility by presenting elastograms recorded from freshly excised human breast
      tissue, including from a mastectomy, lumpectomies and a cavity shaving.

PMID- 27867722
TI  - Feasibility of spatial frequency domain imaging (SFDI) for optically
      characterizing a preclinical oncology model.
AB  - Determination of chemotherapy efficacy early during treatment would provide more
      opportunities for physicians to alter and adapt treatment plans. Diffuse optical
      technologies may be ideally suited to track early biological events following
      chemotherapy administration due to low cost and high information content. We
      evaluated the use of spatial frequency domain imaging (SFDI) to characterize a
      small animal tumor model in order to move towards the goal of endogenous optical
      monitoring of cancer therapy in a controlled preclinical setting. The effects of
      key measurement parameters including the choice of imaging spatial frequency and
      the repeatability of measurements were evaluated. The precision of SFDI optical
      property extractions over repeat mouse measurements was determined to be within
      3.52% for move and replace experiments. Baseline optical properties and
      chromophore values as well as intratumor heterogeneity were evaluated over 25
      tumors. Additionally, tumor growth and chemotherapy response were monitored over
      a 45 day longitudinal study in a small number of mice to demonstrate the ability
      of SFDI to track treatment effects. Optical scattering and oxygen saturation
      increased as much as 70% and 25% respectively in treated tumors, suggesting SFDI
      may be useful for preclinical tracking of cancer therapies.

PMID- 27867723
TI  - All-optical highly sensitive akinetic sensor for ultrasound detection and
      photoacoustic imaging.
AB  - A novel all-optical akinetic ultrasound sensor, consisting of a rigid, fiber
      coupled Fabry-Perot etalon with a transparent central opening is presented. The
      sensing principle relies exclusively on the detection of pressure-induced changes
      of the refractive index in the fluid filling the Fabry-Perot cavity. This enables
      resonance-free, inherently linear signal detection over a broad bandwidth. We
      demonstrate that the sensor achieves a exceptionally low peak noise equivalent
      pressure (NEP) values of 2 Pa over a 20 MHz measurement bandwidth (without signal
      averaging), while maintaining a flat frequency response, and a detection
      bandwidth up to 22.5 MHz (-6 dB). The measured large full field of view of the
      sensor is 2.7 mm * 1.3 mm and the dynamic range is [Formula: see text] or 63 dB
      at 20 MHz bandwidth. For different required amplitude ranges the upper amplitude
      detection limit can be customized from at least 2 kPa to 2 MPa by using cavity
      mirrors with a lower optical reflectivity. Imaging tests on a resolution target
      and on biological tissue show the excellent suitability of the akinetic sensor
      for optical resolution photoacoustic microscopy (OR-PAM) applications.

PMID- 27867724
TI  - Dual-color multiple-particle tracking at 50-nm localization and over 100-um range
      in 3D with temporal focusing two-photon microscopy.
AB  - Nanoscale particle tracking in three dimensions is crucial to directly observe
      dynamics of molecules and nanoparticles in living cells. Here we present a three
      dimensional particle tracking method based on temporally focused two-photon
      excitation. Multiple particles are imaged at 30 frames/s in volume up to 180 *
      180 * 100 um3. The spatial localization precision can reach 50 nm. We demonstrate
      its capability of tracking fast swimming microbes at speed of ~200 um/s. Two
      photon dual-color tracking is achieved by simultaneously exciting two kinds of
      fluorescent beads at 800 nm to demonstrate its potential in molecular interaction
      studies. Our method provides a simple wide-field fluorescence imaging approach
      for deep multiple-particle tracking.

PMID- 27867725
TI  - Phase stretch transform for super-resolution localization microscopy.
AB  - Super-resolution localization microscopy has revolutionized the observation of
      living structures at the cellular scale, by achieving a spatial resolution that
      is improved by more than an order of magnitude compared to the diffraction limit.
      These methods localize single events from isolated sources in repeated cycles in
      order to achieve super-resolution. The requirement for sparse distribution of
      simultaneously activated sources in the field of view dictates the acquisition of
      thousands of frames in order to construct the full super-resolution image. As a
      result, these methods have slow temporal resolution which is a major limitation
      when investigating live-cell dynamics. In this paper we present the use of a
      phase stretch transform for high-density super-resolution localization
      microscopy. This is a nonlinear frequency dependent transform that emulates the
      propagation of light through a physical medium with a specific warped diffractive
      property and applies a 2D phase function to the image in the frequency domain. By
      choosing properly the transform parameters and the phase kernel profile, the
      point spread function of each emitter can be sharpened and narrowed. This enables
      the localization of overlapping emitters, thus allowing a higher density of
      activated emitters as well as shorter data collection acquisition rates. The
      method is validated by numerical simulations and by experimental data obtained
      using a microtubule sample.

PMID- 27867726
TI  - Time-resolved fluorescence spectroscopy for clinical diagnosis of actinic
      cheilitis.
AB  - Actinic cheilitis is a potentially malignant disorder of the lips. Its first
      cause is believed to be UV sun radiation. The lesion is highly heterogeneous,
      making the choice of area to be biopsied difficult. This study exploits the
      capabilities of time-resolved fluorescence spectroscopy for the identification of
      the most representative area to be biopsied. A preliminary study was performed on
      fourteen patients. A classification algorithm was used on data acquired on nine
      different biopsies. The algorithm discriminated between absent, mild, and
      moderate dysplasia with a sensitivity of 92.9%, 90.0%, and 80.0%, respectively.
      The false positive rate for healthy tissue (specificity) was 88.8%.

PMID- 27867727
TI  - Optical lens-microneedle array for percutaneous light delivery.
AB  - The limited penetration depth of light in skin tissues is a practical bottleneck
      in dermatologic applications of light-induced therapies, including anti-microbial
      blue light therapy and photodynamic skin cancer therapy. Here, we demonstrate a
      novel device, termed optical microneedle array (OMNA), for percutaneous light
      delivery. A prototype device with a 11 by 11 array of needles at a spacing of 1
      mm and a length of 1.6 mm was fabricated by press-molding poly-(lactic acid)
      (PLA) polymers. The device also incorporates a matched microlens array that
      focuses the light through the needle tips at specific points to achieve an
      optimal intensity profile in the tissue. In experiments done with bovine tissues,
      the OMNA enabled us to deliver a total of 7.5% of the input photons at a
      wavelength of 491 nm, compared to only 0.85% without the device. This 9-fold
      enhancement of light delivery was close to the prediction of 10.8 dB by ray
      tracing simulation and is expected to increase the effective treatment depth of
      anti-microbial blue light therapy significantly from 1.3 to 2.5 mm in human skin.

PMID- 27867728
TI  - Label free measurement of retinal blood cell flux, velocity, hematocrit and
      capillary width in the living mouse eye.
AB  - Measuring blood cell dynamics within the capillaries of the living eye provides
      crucial information regarding the health of the microvascular network. To date,
      the study of single blood cell movement in this network has been obscured by
      optical aberrations, hindered by weak optical contrast, and often required
      injection of exogenous fluorescent dyes to perform measurements. Here we present
      a new strategy to non-invasively image single blood cells in the living mouse eye
      without contrast agents. Eye aberrations were corrected with an adaptive optics
      camera coupled with a fast, 15 kHz scanned beam orthogonal to a capillary of
      interest. Blood cells were imaged as they flowed past a near infrared imaging
      beam to which the eye is relatively insensitive. Optical contrast of cells was
      optimized using differential scatter of blood cells in the split-detector imaging
      configuration. Combined, these strategies provide label-free, non-invasive
      imaging of blood cells in the retina as they travel in single file in
      capillaries, enabling determination of cell flux, morphology, class, velocity,
      and rheology at the single cell level.

PMID- 27867729
TI  - Binocular summation and visual function with induced anisocoria and monovision.
AB  - The advances in new techniques for correcting presbyopia, such as a small
      aperture combined with monovision, require an in-depth study of binocular
      aspects. In this work, we have studied binocular visual performance of 12
      subjects after inducing different degrees of anisocoria combined with two
      different add powers in the non-dominant eye. We have analysed visual performance
      in terms of the visual-discrimination capacity (a function to evaluate the
      strength of bothersome halos) and the contrast-sensitivity. The results show a
      deterioration of the binocular vision when inducing anisocoria and with any add
      power, with a higher perception of halos, a lower contrast sensitivity and poorer
      binocular summation of these visual functions on increasing anisocoria. This
      deterioration is clinically acceptable in the case of low add power, since
      positive binocular summation is maintained in contrast sensitivity, and visual
      discrimination is not altered.

PMID- 27867730
TI  - Adaptive illumination reduces photobleaching in structured illumination
      microscopy.
AB  - Photobleaching is a major factor limiting the observation time in fluorescence
      microscopy. We achieve photobleaching reduction in structured illumination
      microscopy (SIM) by locally adjusting the illumination intensities according to
      the sample. Adaptive SIM is enabled by a digital micro-mirror device (DMD), which
      provides a projection of the grayscale illumination patterns. We demonstrate a
      reduction in photobleaching by a factor of three in adaptive SIM compared to the
      non-adaptive SIM based on a spot grid scanning approach. Our proof-of-principle
      experiments show great potential for DMD-based microscopes to become a more
      useful tool in live-cell SIM imaging.

PMID- 27867731
TI  - Functional imaging of the human brain using a modular, fibre-less, high-density
      diffuse optical tomography system.
AB  - We present the first three-dimensional, functional images of the human brain to
      be obtained using a fibre-less, high-density diffuse optical tomography system.
      Our technology consists of independent, miniaturized, silicone-encapsulated DOT
      modules that can be placed directly on the scalp. Four of these modules were
      arranged to provide up to 128, dual-wavelength measurement channels over a scalp
      area of approximately 60 * 65 mm2. Using a series of motor-cortex stimulation
      experiments, we demonstrate that this system can obtain high-quality, continuous
      wave measurements at source-detector separations ranging from 14 to 55 mm in
      adults, in the presence of hair. We identify robust haemodynamic response
      functions in 5 out of 5 subjects, and present diffuse optical tomography images
      that depict functional haemodynamic responses that are well-localized in all
      three dimensions at both the individual and group levels. This prototype modular
      system paves the way for a new generation of wearable, wireless, high-density
      optical neuroimaging technologies.

PMID- 27867733
TI  - Multi-wavelength photoplethysmography method for skin arterial pulse extraction.
AB  - In this work, we present a multi-wavelength (MW) PPG method exploiting the
      wavelength dependence of light penetration in skin tissue to provide depth
      resolution of skin blood pulsation. The MW PPG system requires two to three light
      sources in different wavelengths and extracts the arterial blood pulsation
      through a multi-wavelength multi-layer light-skin interaction model, which
      removes the capillary pulsation (determined from the short-wavelength PPG signal)
      from the long-wavelength PPG signal using absorption weighting factors that are
      quasi-analytically calibrated. The extracted pulsations are used to calculate
      blood pressure (BP) through pulse transit time (PTT), and the results are
      compared with those obtained from the single wavelength PPG method. The
      comparative study is clinically performed on 20 subjects including 10 patients
      diagnosed with cardiovascular diseases and 10 healthy subjects. The result
      demonstrates that the MW PPG method significantly improves the measurement
      accuracy of systolic BP (SBP), reducing the mean absolute difference between the
      reference and the estimated SBP values from 5.7 mmHg (for single-wavelength PPG)
      to 2.9 mmHg (for three-wavelength PPG).

PMID- 27867734
TI  - In vitro hematocrit measurement using spectrally encoded flow cytometry.
AB  - Measuring key physiological parameters of small blood samples extracted from
      patients could be useful for real-time clinical diagnosis at the point of care.
      An important parameter required from all blood tests is the blood hematocrit, a
      measure of the fractional volume occupied by the red cells within the blood. In
      this work, we present a method for in vitro evaluation of hematocrit based on the
      data acquired using spectrally encoded flow cytometry. Analysis of the
      reflectance confocal images of blood within a flow chamber resulted in an error
      as low as 1.7% in the measured hematocrit. The technique could be used as part of
      an in vitro diagnostic system that measures important blood parameters at the
      point of care.

PMID- 27867735
TI  - Spectrally-broad coherent anti-Stokes Raman scattering hyper-microscopy utilizing
      a Stokes supercontinuum pumped at 800 nm.
AB  - We demonstrate spectral-focusing based coherent anti-Stokes Raman scattering (SF
      CARS) hyper-microscopy capable of probing vibrational frequencies from 630 cm-1
      to 3250 cm-1 using a single Ti:Sapphire femtosecond laser operating at 800 nm,
      and a commercially-available supercontinuum-generating fibre module. A broad
      Stokes supercontinuum with significant spectral power at wavelengths between 800
      nm and 940 nm is generated by power tuning the fibre module using atypically long
      and/or chirped ~200 fs pump pulses, allowing convenient access to lower
      vibrational frequencies in the fingerprint spectral region. This work
      significantly reduces the instrumental and technical requirements for multimodal
      CARS microscopy, while expanding the spectral capabilities of an established
      approach to SF-CARS.

PMID- 27867732
TI  - Dynamic contrast optical coherence tomography images transit time and quantifies
      microvascular plasma volume and flow in the retina and choriocapillaris.
AB  - Despite the prevalence of optical imaging techniques to measure hemodynamics in
      large retinal vessels, quantitative measurements of retinal capillary and
      choroidal hemodynamics have traditionally been challenging. Here, a new imaging
      technique called dynamic contrast optical coherence tomography (DyC-OCT) is
      applied in the rat eye to study microvascular blood flow in individual retinal
      and choroidal layers in vivo. DyC-OCT is based on imaging the transit of an
      intravascular tracer dynamically as it passes through the field-of-view.
      Hemodynamic parameters can be determined through quantitative analysis of tracer
      kinetics. In addition to enabling depth-resolved transit time, volume, and flow
      measurements, the injected tracer also enhances OCT angiograms and enables clear
      visualization of the choriocapillaris, particularly when combined with a post
      processing method for vessel enhancement. DyC-OCT complements conventional OCT
      angiography through quantification of tracer dynamics, similar to fluorescence
      angiography, but with the important added benefit of laminar resolution.

PMID- 27867736
TI  - Quantification in time-domain diffuse optical tomography using Mellin-Laplace
      transforms.
AB  - Simulations and phantom measurements are used to evaluate the ability of time
      domain diffuse optical tomography using Mellin-Laplace transforms to quantify the
      absorption perturbation of centimetric objects immersed at depth 1-2 cm in turbid
      media. We find that the estimated absorption coefficient varies almost linearly
      with the absorption change in the range of 0-0.15 cm-1 but is underestimated by a
      factor that depends on the inclusion depth (~2, 3 and 6 for depths of 1.0, 1.5
      and 2.0 cm respectively). For larger absorption changes, the variation is
      sublinear with ~20% decrease for deltaMUa = 0.37 cm-1. By contrast, constraining
      the absorption change to the actual volume of the inclusion may considerably
      improve the accuracy and linearity of the reconstructed absorption.

PMID- 27867737
TI  - Developing the Philippines as a Global Hub for Disaster Risk Reduction - A Health
      Research Initiative as Presented at the 10th Philippine National Health Research
      System Week Celebration.
AB  - The recent Philippine National Health Research System (PNHRS) Week Celebration
      highlighted the growing commitment to Disaster Risk Reduction (DRR) in the
      Philippines. The event was lead by the Philippine Council for Health Research and
      Development of the Department of Science and Technology and the Department of
      Health, and saw the participation of national and international experts in DRR,
      and numerous research consortia from all over the Philippines. With a central
      focus on the Sendai Framework for Disaster Risk Reduction, the DRR related events
      recognised the significant disaster risks faced in the Philippines. They also
      illustrated the Philippine strengths and experience in DRR. Key innovations in
      science and technology showcased at the conference include the web-base hazard
      mapping applications 'Project NOAH' and 'FaultFinder'. Other notable innovations
      include 'Surveillance in Post Extreme Emergencies and Disasters' (SPEED) which
      monitors potential outbreaks through a syndromic reporting system. Three areas
      noted for further development in DRR science and technology included: integrated
      national hazard assessment, strengthened collaboration, and improved
      documentation. Finally, the event saw the proposal to develop the Philippines
      into a global hub for DRR. The combination of the risk profile of the
      Philippines, established national structures and experience in DRR, as well as
      scientific and technological innovation in this field are potential factors that
      could position the Philippines as a future global leader in DRR. The purpose of
      this article is to formally document the key messages of the DRR-related events
      of the PNHRS Week Celebration.

PMID- 27867738
TI  - Evaluation of electrical impedance spectroscopy as an adjunct to dermoscopy in
      short-term monitoring of atypical melanocytic lesions.
AB  - BACKGROUND: Early detection of melanoma is vital for treatment outcome and
      survival. Short-term sequential digital dermoscopic monitoring (ST-SDDM) involves
      the capture and assessment of dermoscopic images of one or more atypical
      melanocytic lesions (AMLs), at baseline and after four months, in order to detect
      early morphologic changes. Electrical impedance spectroscopy (EIS) is a
      diagnostic tool with high sensitivity for the detection of malignant melanocytic
      lesions. OBJECTIVES: The aim of this study was to assess whether EIS, in addition
      to ST-SDDM, could improve the selection of AMLs requiring surgery. METHODS: In
      this retrospective descriptive study, 22 AMLs in 19 patients were monitored with
      both ST-SDDM and EIS. A modified EIS decision-making algorithm was established.
      AMLs were excised if any dermoscopic changes were seen and/or if the EIS score
      had increased significantly at follow-up. Statistical analyses were made
      including sensitivity, specificity, PPV and NPV. RESULTS: A total of seven
      lesions (32%) were excised. Four lesions (57%) were excised solely because of
      dermoscopic changes including a 0.4 mm-thick melanoma and three benign nevi.
      Three benign lesions (43%) were excised because of increased EIS scores without
      any dermoscopic changes. The EIS scores at follow-up showed high variability as
      compared to the initial scores. CONCLUSION: The addition of EIS to ST-SDDM did
      not identify additional malignant lesions. There was no correlation between
      dermoscopic changes seen with ST-SDDM and increased EIS scores. Three
      histopathologically benign lesions were needlessly excised. Moreover, the low
      reproducibility and the possible interoperator variability of the method raised
      concerns.

PMID- 27867740
TI  - Regressing basal-cell carcinoma masquerading as benign lichenoid keratosis.
AB  - BACKGROUND: Benign lichenoid keratosis (BLK, LPLK) is often misdiagnosed
      clinically as superficial basal-cell carcinoma (BCC), especially when occurring
      on the trunk. However, BCCs undergoing regression may be associated with a
      lichenoid interface dermatitis that may be misinterpreted as BLK in
      histopathologic sections. METHODS: In order to assess the frequency of remnants
      of BCC in lesions interpreted as BLK, we performed step sections on 100 lesions
      from the trunk of male patients that had been diagnosed as BLK. RESULTS: Deeper
      sections revealed remnants of superficial BCC in five and remnants of a
      melanocytic nevus in two specimens. In the original sections of cases in which a
      BCC showed up, crusts tended to be more common, whereas vacuolar changes at the
      dermo-epidermal junction and melanophages in the papillary dermis tended to be
      less common and less pronounced. CONCLUSIONS: Lesions from the trunk submitted as
      BCC and presenting histopathologically as a lichenoid interface dermatitis are
      not always BLKs. Although no confident recommendations can be given on the basis
      of this limited study, deeper sections may be warranted if lesions are crusted
      and/or associated with only minimal vacuolar changes at the dermo-epidermal
      junction and no or few melanophages in the papillary dermis.

PMID- 27867741
TI  - Pityriasis rubra pilaris-like eruption following insulin therapy initiation.
AB  - Pityriasis rubra pilaris (PRP) is a chronic disorder of keratinization of unclear
      pathogenesis. PRP-like eruptions induced by drugs have rarely been described. A
      previously healthy 29-year-old man presented with a generalized, rapidly
      spreading, erythematosquamous dermatosis, that started three days after
      initiation of subcutaneous insulin therapy for diabetes mellitus type 1. Clinical
      and histopathological features were consistent with a PRP-like eruption, possibly
      due to insulin therapy. The patient was switched to insulin analogue therapy and
      a complete healing of all lesions was achieved after two months. No recurrence
      was seen after one year of follow-up. Other possible etiologies of PRP were
      excluded. The mechanism leading to the occurrence of drug-induced PRP-like
      eruptions are not clear. Since PRP may occur in the context of immunological
      anomalies, it is possible that diabetes mellitus type 1 may have been a
      predisposing condition for the development of PRP in this case.

PMID- 27867739
TI  - Dermoscopic hemorrhagic dots: an early predictor of response of psoriasis to
      biologic agents.
AB  - BACKGROUND: Biologic agents are routinely used in the treatment of severe
      psoriasis. The evaluation of treatment response is mainly based on the
      physician's global clinical assessment. OBJECTIVE: To investigate whether
      dermoscopy might enhance the assessment of response of psoriasis to treatment
      with biologic agents. METHODS: Patients with severe psoriasis scheduled to
      receive a biologic agent were enrolled in the study. A target lesion from each
      patient was clinically and dermoscopically documented at baseline and after one,
      two and six months. The clinical response was evaluated by the recruiting
      clinicians at all visits, while dermoscopic images were evaluated by two
      independent investigators, blinded to the clinical information. Chi Square test
      was used for cross-tabulation comparisons, while odds ratios, 95% confidence
      intervals and p values were calculated using univariate logistic regression.
      RESULTS: Overall, there was a significant correlation between clinical response
      and vessel distribution at all time points: a regular vessel distribution
      correlated with no response, a clustered distribution with partial response, and
      the dermoscopic absence of vessels with complete response. The presence of
      dermoscopic hemorrhagic dots was a potent predictor of favorable clinical
      response at the subsequent visit at all time points. Among lesions initially
      clinically responding and later recurring, 87.5% displayed dermoscopic dotted
      vessels despite the macroscopic remission. CONCLUSION: Dermoscopy might be a
      useful additional tool for evaluating the response of psoriatic patients to
      biologic agents. Hemorrhagic dots represent an early predictor of clinical
      response, while the persistence or reappearance of dotted vessels might predict
      clinical persistence or recurrence, respectively.

PMID- 27867742
TI  - Dermoscopic appearance of an amelanotic mucosal melanoma.
AB  - BACKGROUND: Hypomelanotic or amelanotic melanomas are challenging to identify,
      especially at mucosal sites. The dermoscopic clues to the diagnosis of mucosal
      melanomas have been reported to be structureless zones with the presence of blue,
      gray, or white colors. CASE: A female in her seventies noted a new lesion on the
      inside of her right labia that first appeared two months prior. Her past medical
      history was significant for rheumatoid arthritis requiring ongoing treatment with
      methotrexate for 20 years and adalimumab for 10 years. After no response to two
      weeks of local treatment for suspected herpes simplex infection, her gynecologist
      performed a skin biopsy. Based on the histopathological diagnosis of an
      amelanotic melanoma (Breslow thickness of 1.3 mm) the patient was referred to
      dermatology for further assessment. Polarized dermoscopy revealed a distinct
      asymmetric, sharply demarcated homogenous white papule (4 * 5 mm) as well as
      polymorphous vessels. CONCLUSION: Dermoscopy may aid in the diagnosis of
      amelanotic mucosal melanomas. Our case revealed a structureless white area and
      polymorphous vessels. Additional clues to the diagnosis were the advanced age of
      the patient and the clinical presentation of a new lesion.

PMID- 27867743
TI  - In vivo reflectance confocal microscopy features of a melanoacanthoma.
AB  - Efforts have been expended to evaluate the reflectance confocal microscopy (RCM)
      features of different clinical entities in order to more thoroughly delineate
      benign versus malignant features. In this way, RCM can help clinicians to be more
      selective in regard to undertaking appropriate skin biopsies and improving their
      benign to malignant ratio. Herein, we report a case of a histopathologically
      proven melanoacanthoma, a variant of seborrheic keratosis. There are scarce
      reports describing the RCM features of melanoacanthoma. Our case demonstrated RCM
      features that were suspicious for melanoma. More RCM images of this benign entity
      are needed to establish definitive diagnostic criteria.

PMID- 27867744
TI  - IgA pemphigus showing IgA antibodies to desmoglein 1 and 3.
AB  - BACKGROUND: IgA pemphigus is a rare autoimmune vesiculo-pustular skin disease.
      Only approximately 70 cases have been reported to date. We report a case of IgA
      pemphigus with IgA antibodies to desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3).
      CASE REPORT: We report the case of an 60-year-old man with intraepidermal
      neutrophilic IgA pemphigus with IgA antibodies to Dsg1 and Dsg3. Histologic
      examination revealed subcorneal neutrophilic pustules with few acantholytic
      cells. The disease was not effectively controlled by conventional therapeutic
      regimens (colchicine, dapsone). Systemic treatment with isotretinoin 25 mg/d and
      prednisone 20 mg/d achieved only a slight effect after six months. CONCLUSIONS:
      Our case confirmed the recalcitrant nature of IgA pemphigus in response to
      distinct therapies, indicating that further research focusing on therapeutic
      approaches for this type of pemphigus is needed. Physicians should keep IgA
      pemphigus in mind when approaching patients with bullous eruption.

PMID- 27867745
TI  - First description of the dermatoscopic features of acquired elastotic hemangioma
      a case report.
AB  - We present a case of acquired elastotic hemangioma (AEH), a rare, benign vascular
      tumor. A Caucasian male in his 60s presented with an asymptomatic, solitary, non
      pigmented and violaceous lesion of short duration on the dorsum of his hand. The
      lesion had unique clinical, dermatoscopic and pathological features.
      Dermatoscopic images of the lesion are presented for characterization and
      histopathological correlation that have not previously been published or
      described.

PMID- 27867746
TI  - Atypical case of lichen planus recognized by dermoscopy.
AB  - Lichen planus (LP) is an inflammatory disease that affects the skin-mainly the
      extremities and the trunk-the mucous membranes, the genitalia, the nails and the
      scalp. The diagnosis of LP is usually established clinically based on the typical
      morphology and distribution of the lesions in conjunction with the associated
      itch. We report a patient with LP manifesting highly psoriasiform lesions, that
      could only be correctly assessed after the application of dermoscopy, which
      revealed LP-specific findings.

PMID- 27867747
TI  - Early diagnosis of genital mucosal melanoma: how good are our dermoscopic
      criteria?
AB  - BACKGROUND: There are limited studies on the dermoscopic features of mucosal
      melanoma, particularly early-stage lesions. Described criteria include the
      presence of blue, gray, or white colors, with a reported sensitivity of 100%. It
      is unclear if these features will aid in the detection of early mucosal melanoma
      or improve diagnostic accuracy compared to naked-eye examination alone. CASE: An
      Asian female in her fifties was referred for evaluation of an asymptomatic,
      irregularly pigmented patch of the clitoral hood and labia minora of unknown
      duration. Her past medical history was notable for Stage IV non-small cell lung
      cancer. She denied a personal or family history of skin cancer. Dermoscopic
      evaluation of the vulvar lesion revealed heterogeneous brown and black
      pigmentation mostly composed of thick lines. There were no other colors or
      structures present. As the differential diagnosis included vulvar melanosis and
      mucosal melanoma, the patient was recommended to undergo biopsy, which was
      delayed due to complications from her underlying lung cancer. Repeat dermoscopic
      imaging performed three months later revealed significant changes concerning for
      melanoma, including increase in size, asymmetric darkening, and the appearance of
      structureless areas and central blue and pink colors. Histopathological
      examination of a biopsy and subsequent resection confirmed the diagnosis of
      melanoma in situ. CONCLUSION: Previously described dermoscopic features for
      mucosal melanoma may not have high sensitivity for early melanomas. Additional
      studies are needed to define the dermoscopic characteristics of mucosal melanomas
      that aid in early detection. Health care providers should have a low threshold
      for biopsy of mucosal lesions that show any clinical or dermoscopic features of
      melanoma, especially in older women.

PMID- 27867748
TI  - Pigmented Bowen's disease presenting with a "starburst" pattern.
AB  - Pigmented Bowen's disease (pBD) is an uncommon in situ squamous cell carcinoma of
      the skin usually presenting as a dark scaly plaque involving chronically exposed
      sites, which is not uncommonly mistaken for other similar pigmented lesions, such
      as melanoma, pigmented basal cell carcinoma or seborrheic keratosis [1,2].
      Dermoscopy has been proven to improve its diagnosis by showing several findings,
      i.e., gray/brownish dots in linear arrangement, scales, coiled vessels,
      focal/multifocal amorphous hypopigmentation and bluish structureless areas [1,2].
      However, pBD may sometimes display dermoscopic features which are typical of
      other pigmented lesions, thus making its recognition quite troublesome despite
      the use of dermoscopy [1,2]. We report a case of pBD with a "starburst" pattern,
      discussing its dermoscopic differential diagnosis.

PMID- 27867749
TI  - An irregular pigmented lesion on the back.

PMID- 27867750
TI  - Ethics, Risk, and Media Intervention: Women's Breast Cancer in Venezuela.
AB  - Breast cancer incidence and mortality rates are of concern among Latin American
      women, mainly due to the growing prevalence of this disease and the lack of
      compliance to proper breast cancer screening and treatment. Focusing on
      Venezuelan women and the challenges and barriers that interact with their health
      communication, this paper looks into issues surrounding women's breast cancer,
      such as the challenges and barriers to breast cancer care, the relevant ethics
      and responsibilities, the right to health, breast cancer risk perception and risk
      communication, and the media interventions that affect Venezuelan women's
      perceptions and actions pertaining to this disease. In particular, it describes
      an action-oriented research project in Venezuela that was conducted over a four
      year period of collaborative work among researchers, practitioners, NGOs,
      patients, journalists, and policymakers. The outcomes include positive
      indications on more effective interactions between physicians and patients,
      increasing satisfactions about issues of ethical treatment in providing
      healthcare services, more sufficient and responsible media coverage of breast
      cancer healthcare services and information, a widely supported declaration for a
      national response against breast cancer in Venezuela, and the creation of a code
      of ethics for the Venezuelan NGO that led the expansion of networking in support
      of women's breast cancer healthcare.

PMID- 27867751
TI  - T7 Phage Display Library a Promising Strategy to Detect Tuberculosis Specific
      Biomarkers.
AB  - One-third of the world's population is infected with tuberculosis, only 10% will
      develop active disease and the remaining 90% is considered to have latent TB
      (LTB). While active TB is contagious and can be lethal, the LTB can evolve to
      active TB. The diagnosis of TB can be challenging, especially in the early
      stages, due to the variability in presentation and nonspecific signs and
      symptoms. Currently, we have limited tools available to diagnose active TB,
      predict treatment efficacy and cure of active tuberculosis, the reactivation of
      latent tuberculosis infection, and the induction of protective immune responses
      through vaccination. Therefore, the identification of robust and accurate
      tuberculosis-specific biomarkers is crucial for the successful eradication of TB.
      In this commentary, we summarized the available methods for diagnosis and
      differentiation of active TB from LTB and their limitations. Additionally, we
      present a novel peptide microarray platform as promising strategy to identify TB
      biomarkers.

PMID- 27867753
TI  - Diabetic Wounds Exhibit Decreased Ym1 and Arginase Expression with Increased
      Expression of IL-17 and IL-20.
AB  - Objective: Impaired wound healing in diabetic (DB) patients is a significant
      health problem; however, the roles that cytokines and innate immune cells
      contribute to this impaired healing are not completely understood. Approach: A
      mouse model was used to compare the innate immune response during DB and normal
      wound healing. Two 5-mm full-thickness wounds were created on the dorsal skin of
      BKS.Cg-m+/+Leprdb/J (DB) and C57BL/6 (wild-type) mice. Innate immune cell markers
      and cytokine mRNA levels were measured in wound biopsies during the first week of
      healing. Results: Innate immune cell influx (typified by the Gr-1 neutrophil
      marker and the Ym1 macrophage marker) was delayed in the DB wounds. Expression of
      the M2 macrophage-related genes, Ym1 and arginase 1, was significantly reduced in
      the DB wounds. PCR array analysis demonstrated altered cytokine expression in DB
      wounds. Most prominently, both interleukin (IL)-17 and IL-20 mRNA levels were
      significantly increased in the DB wounds. Innovation: This is the first study to
      identify increased levels of IL-17 and IL-20 in DB wounds. These cytokines are
      also elevated in the inflammatory skin disorder, psoriasis; thus, they may be
      potential therapeutic targets to aid in DB wound healing. Conclusion: The entire
      cytokine profile of DB wounds over the course of healing is not completely
      understood. This study suggests that the IL-17 and IL-20 families of cytokines
      should be further analyzed in the context of DB wound healing.

PMID- 27867752
TI  - Comparing the Effectiveness of Polymer Debriding Devices Using a Porcine Wound
      Biofilm Model.
AB  - Objective: Debridement to remove necrotic and/or infected tissue and promote
      active healing remains a cornerstone of contemporary chronic wound management.
      While there has been a recent shift toward less invasive polymer-based debriding
      devices, their efficacy requires rigorous evaluation. Approach: This study was
      designed to directly compare monofilament debriding devices to traditional gauze
      using a wounded porcine skin biofilm model with standardized application
      parameters. Biofilm removal was determined using a surface viability assay,
      bacterial counts, histological assessment, and scanning electron microscopy
      (SEM). Results: Quantitative analysis revealed that monofilament debriding
      devices outperformed the standard gauze, resulting in up to 100-fold greater
      reduction in bacterial counts. Interestingly, histological and morphological
      analyses suggested that debridement not only removed bacteria, but also
      differentially disrupted the bacterially-derived extracellular polymeric
      substance. Finally, SEM of post-debridement monofilaments showed structural
      changes in attached bacteria, implying a negative impact on viability.
      Innovation: This is the first study to combine controlled and defined debridement
      application with a biologically relevant ex vivo biofilm model to directly
      compare monofilament debriding devices. Conclusion: These data support the use of
      monofilament debriding devices for the removal of established wound biofilms and
      suggest variable efficacy towards biofilms composed of different species of
      bacteria.

PMID- 27867754
TI  - A Small Chimeric Fibronectin Fragment Accelerates Dermal Wound Repair in Diabetic
      Mice.
AB  - Objective: During wound repair, soluble fibronectin is converted into
      biologically active, insoluble fibrils via a cell-mediated process. This
      fibrillar, extracellular matrix (ECM) form of fibronectin stimulates cell
      processes critical to tissue repair. Nonhealing wounds show reduced levels of ECM
      fibronectin fibrils. The objective of this study was to produce a small,
      recombinant wound supplement with the biological activity of insoluble
      fibronectin fibrils. Approach: A chimeric fibronectin fragment was produced by
      inserting the integrin-binding Arg-Gly-Asp (RGD) loop from the tenth type III
      repeat of fibronectin (FNIII10) into the analogous site within the heparin
      binding, bioactive fragment of the first type III repeat (FNIII1H). FNIII1HRGD
      was tested for its ability to support cell functions necessary for wound healing,
      and then evaluated for its capacity to accelerate healing of full-thickness
      dermal wounds in diabetic mice. Results:In vitro, FNIII1HRGD supported cell
      adhesion, proliferation, and ECM fibronectin deposition. Application of
      FNIII1HRGD to dermal wounds of diabetic mice significantly enhanced wound closure
      compared with controls (73.9% +/-4.1% vs. 58.1% +/-4.7% closure on day 9,
      respectively), and significantly increased granulation tissue thickness (2.88 +/-
      0.75-fold increase over controls on day 14). Innovation: Recombinant proteins
      designed to functionally mimic the ECM form of fibronectin provide a novel
      therapeutic approach to circumvent diminished fibronectin fibril formation by
      delivering ECM fibronectin signals in a soluble form to chronic wounds.
      Conclusion: A small, chimeric fibronectin protein was developed. FNIII1HRGD
      demonstrated enhanced bioactivity in vitro and stimulated wound repair in a
      murine model of chronic wounds.

PMID- 27867755
TI  - Nutritional Aspects of Gastrointestinal Wound Healing.
AB  - Significance: Although the wound healing cascade is similar in many tissues, in
      the gastrointestinal tract mucosal healing is critical for processes such as
      inflammatory bowel disease and ulcers and healing of the mucosa, submucosa, and
      serosal layers is needed for surgical anastomoses and for enterocutaneous
      fistula. Failure of wound healing can result in complications including
      infection, prolonged hospitalization, critical illness, organ failure,
      readmission, new or worsening enterocutaneous fistula, and even death. Recent
      Advances: Recent advances are relevant for the role of specific micronutrients,
      such as vitamin D, trace elements, and the interplay between molecules with pro-
      and antioxidant properties. Our understanding of the role of other small
      molecules, genes, proteins, and macronutrients is also rapidly changing. Recent
      work has elucidated relationships between oxidative stress, nutritional
      supplementation, and glucose metabolism. Thresholds have also been established to
      define adequate preoperative nutritional status. Critical Issues: Further work is
      needed to establish standards and definitions for measuring the extent of wound
      healing, particularly for inflammatory bowel disease and ulcers. In addition, a
      mounting body of evidence has determined the need for adequate preoperative
      nutritional supplementation for elective surgical procedures. Future Directions:
      A large portion of current work is restricted to model systems in rodents.
      Therefore, additional clinical and translational research is needed in this area
      to promote gastrointestinal wound healing in humans, particularly those suffering
      from critical illness, patients with enterocutaneous fistula, inflammatory bowel
      disease, and ulcers, and those undergoing surgical procedures.

PMID- 27867756
TI  - Reference Clinical Database for Fixation Stability Metrics in Normal Subjects
      Measured with the MAIA Microperimeter.
AB  - PURPOSE: The purpose of this study was to establish a normal reference database
      for fixation stability measured with the bivariate contour ellipse area (BCEA) in
      the Macular Integrity Assessment (MAIA) microperimeter. METHODS: Subjects were
      358 healthy volunteers who had the MAIA examination. Fixation stability was
      assessed using two BCEA fixation indices (63% and 95% proportional values) and
      the percentage of fixation points within 1 degrees  and 2 degrees  from the fovea
      (P1 and P2). Statistical analysis was performed with linear regression and
      Pearson's product moment correlation coefficient. RESULTS: Average areas of 0.80
      deg2 (min = 0.03, max = 3.90, SD = 0.68) for the index BCEA@63% and 2.40 deg2
      (min = 0.20, max = 11.70, SD = 2.04) for the index BCEA@95% were found. The
      average values of P1 and P2 were 95% (min = 76, max = 100, SD = 5.31) and 99%
      (min = 91, max = 100, SD = 1.42), respectively. The Pearson's product moment test
      showed an almost perfect correlation index, r = 0.999, between BCEA@63% and
      BCEA@95%. Index P1 showed a very strong correlation with BCEA@63%, r = -0.924, as
      well as with BCEA@95%, r = -0.925. Index P2 demonstrated a slightly lower
      correlation with both BCEA@63% and BCEA@95%, r = -0.874 and -0.875, respectively.
      CONCLUSIONS: The single parameter of the BCEA@95% may be taken as accurately
      reporting fixation stability and serves as a reference database of normal
      subjects with a cutoff area of 2.40 +/- 2.04 deg2 in MAIA microperimeter.
      TRANSLATIONAL RELEVANCE: Fixation stability can be measured with different
      indices. This study originates reference fixation values for the MAIA using a
      single fixation index.

PMID- 27867757
TI  - Epigenetics, Media Coverage, and Parent Responsibilities in the Post-Genomic Era.
AB  - Environmental epigenetics is the study of how exposures and experiences can turn
      genes "on" or "off" without changing DNA sequence. By examining the influence
      that environmental conditions including diet, stress, trauma, toxins, and care
      can have on gene expression, this science suggests molecular connections between
      the environment, genetics, and how acquired characteristics may be inherited
      across generations. The rapid expansion of research in this area has attracted
      growing media attention. This coverage has implications for how parents and
      prospective parents understand health and their perceived responsibilities for
      children's wellbeing. This review provides insight into epigenetic research, its
      coverage in the media, and the social and ethical implications of this science
      for patients and clinicians. As epigenetic findings continue to elucidate the
      complex relationships between nature and nurture, it becomes critical to examine
      how representations of this science may influence patient experiences of risk and
      responsibility. This review describes some of the social and ethical implications
      of epigenetic research today.

PMID- 27867759
TI  - The potential for self-seeding by the coral Pocillopora spp. in Moorea, French
      Polynesia.
AB  - Coral reefs in Moorea, French Polynesia, suffered catastrophic coral mortality
      through predation by Acanthaster planci from 2006 to 2010, and Cyclone Oli in
      2010, yet by 2015 some coral populations were approaching pre-disturbance sizes.
      Using long-term study plots, we quantified population dynamics of spawning
      Pocillopora spp. along the north shore of Moorea between 2010 and 2014, and
      considered evidence that population recovery could be supported by self-seeding.
      Results scaled up from study plots and settlement tiles suggest that the number
      of Pocillopora spp. colonies on the outer reef increased 1,890-fold between 2010
      and 2014/2015, and in the back reef, 8-fold between 2010 and 2014/2015. Assuming
      that spawning Pocillopora spp. in Moorea release similar numbers of eggs as con
      generics in Hawaii, and fertilization success is similar to other spawning
      corals, the capacity of Pocillopora spp. to produce larvae was estimated. These
      estimates suggest that Pocillopora spp. in Moorea produced a large excess of
      larvae in 2010 and 2014 relative to the number required to produce the recruits
      found in the back reef and outer reef in 2010 and 2014, even assuming that ~99.9%
      of the larvae do not recruit in Moorea. Less than a third of the recruits in one
      year would have to survive to produce the juvenile Pocillopora spp. found in the
      back and outer reefs in 2010 and 2014/2015. Our first order approximations reveal
      the potential for Pocillopora spp. on the north shore of Moorea to produce enough
      larvae to support local recruitment and population recovery following a
      catastrophic disturbance.

PMID- 27867758
TI  - Naturally Occurring Changes in Estradiol Concentrations in the Menopause
      Transition Predict Morning Cortisol and Negative Mood in Perimenopausal
      Depression.
AB  - Risk of depression increases considerably during the menopause transition (or
      perimenopause) - the 5-6 years surrounding the last menstrual period. While the
      mechanisms underlying this increased risk are unknown, we have hypothesized that
      excessive estradiol (E2) fluctuation, which accompanies the perimenopause, may be
      implicated. We have furthermore proposed that dysregulation of the hypothalamic
      pituitary-adrenal (HPA) axis may underlie E2 fluctuation's effect on mood. This
      study examined the relationship between weekly changes in salivary E2, salivary
      cortisol levels and weekly mood in 30 perimenopausal women recruited to achieve
      equal numbers of women with current depression, past depression, and no history
      of depression. Greater weekly increases in E2 were associated with increased
      cortisol among past and currently depressed women; greater E2 increases were also
      associated with negative mood among currently depressed women. These findings
      provide evidence that HPA axis dysregulation, correlated with E2 fluctuation, may
      be implicated in the pathophysiology of perimenopausal depression.

PMID- 27867760
TI  - Pico and nanoplankton abundance and carbon stocks along the Brazilian Bight.
AB  - Pico and nanoplankton communities from the Southwest Atlantic Ocean along the
      Brazilian Bight are poorly described. The hydrography in this region is dominated
      by a complex system of layered water masses, which includes the warm and
      oligotrophic Tropical Water (TW), the cold and nutrient rich South Atlantic
      Central Water (SACW) and the Coastal Water (CW), which have highly variable
      properties. In order to assess how pico- and nanoplankton communities are
      distributed in these different water masses, we determined by flow cytometry the
      abundance of heterotrophic bacteria, Prochlorococcus, Synechococcus and
      autotrophic pico and nanoeukaryotes along three transects, extending from 23
      degrees S to 31 degrees S and 39 degrees W to 49 degrees W. Heterotrophic
      bacteria (including archaea, maximum of 1.5 * 106 cells mL-1) were most abundant
      in Coastal and Tropical Water whereas Prochlorococcus was most abundant in open
      ocean oligotrophic waters (maximum of 300 * 103 cells mL-1). Synechococcus(up to
      81 * 103 cells mL-1), as well as autotrophic pico and nanoeukaryotes seemed to
      benefit from the influx of nutrient-rich waters near the continental slope.
      Autotrophic pico and nanoeukaryotes were also abundant in deep chlorophyll
      maximum (DCM) layers from offshore waters, and their highest abundances were 20 *
      103 cells mL-1 and 5 * 103 cells mL-1, respectively. These data are consistent
      with previous observations in other marine areas where Synechococcus and
      autotrophic eukaryotes dominate mesotrophic waters, whereas Prochlorococcus
      dominate in more oligotrophic areas. Regardless of the microbial community
      structure near the surface, the carbon stock dominance by autotrophic
      picoeukaryotes near the DCM is possibly linked to vertical mixing of oligotrophic
      surface waters with the nutrient-rich SACW and their tolerance to lower light
      levels.

PMID- 27867761
TI  - Hyainailourine and teratodontine cranial material from the late Eocene of Egypt
      and the application of parsimony and Bayesian methods to the phylogeny and
      biogeography of Hyaenodonta (Placentalia, Mammalia).
AB  - Hyaenodonta is a diverse, extinct group of carnivorous mammals that included
      weasel- to rhinoceros-sized species. The oldest-known hyaenodont fossils are from
      the middle Paleocene of North Africa and the antiquity of the group in Afro
      Arabia led to the hypothesis that it originated there and dispersed to Asia,
      Europe, and North America. Here we describe two new hyaenodont species based on
      the oldest hyaenodont cranial specimens known from Afro-Arabia. The material was
      collected from the latest Eocene Locality 41 (L-41, ~34 Ma) in the Fayum
      Depression, Egypt. Akhnatenavus nefertiticyon sp. nov. has specialized,
      hypercarnivorous molars and an elongate cranial vault. In A. nefertiticyon the
      tallest, piercing cusp on M1-M2 is the paracone. Brychotherium ephalmos gen. et
      sp. nov. has more generalized molars that retain the metacone and complex
      talonids. In B. ephalmos the tallest, piercing cusp on M1-M2 is the metacone. We
      incorporate this new material into a series of phylogenetic analyses using a
      character-taxon matrix that includes novel dental, cranial, and postcranial
      characters, and samples extensively from the global record of the group. The
      phylogenetic analysis includes the first application of Bayesian methods to
      hyaenodont relationships. B. ephalmos is consistently placed within
      Teratodontinae, an Afro-Arabian clade with several generalist and
      hypercarnivorous forms, and Akhnatenavus is consistently recovered in
      Hyainailourinae as part of an Afro-Arabian radiation. The phylogenetic results
      suggest that hypercarnivory evolved independently three times within Hyaenodonta:
      in Teratodontinae, in Hyainailourinae, and in Hyaenodontinae. Teratodontines are
      consistently placed in a close relationship with Hyainailouridae (Hyainailourinae
      + Apterodontinae) to the exclusion of "proviverrines," hyaenodontines, and
      several North American clades, and we propose that the superfamily
      Hyainailouroidea be used to describe this relationship. Using the topologies
      recovered from each phylogenetic method, we reconstructed the biogeographic
      history of Hyaenodonta using parsimony optimization (PO), likelihood optimization
      (LO), and Bayesian Binary Markov chain Monte Carlo (MCMC) to examine support for
      the Afro-Arabian origin of Hyaenodonta. Across all analyses, we found that
      Hyaenodonta most likely originated in Europe, rather than Afro-Arabia. The clade
      is estimated by tip-dating analysis to have undergone a rapid radiation in the
      Late Cretaceous and Paleocene; a radiation currently not documented by fossil
      evidence. During the Paleocene, lineages are reconstructed as dispersing to Asia,
      Afro-Arabia, and North America. The place of origin of Hyainailouroidea is likely
      Afro-Arabia according to the Bayesian topologies but it is ambiguous using
      parsimony. All topologies support the constituent clades-Hyainailourinae,
      Apterodontinae, and Teratodontinae-as Afro-Arabian and tip-dating estimates that
      each clade is established in Afro-Arabia by the middle Eocene.

PMID- 27867762
TI  - A global analysis of bird plumage patterns reveals no association between habitat
      and camouflage.
AB  - Evidence suggests that animal patterns (motifs) function in camouflage. Irregular
      mottled patterns can facilitate concealment when stationary in cluttered
      habitats, whereas regular patterns typically prevent capture during movement in
      open habitats. Bird plumage patterns have predominantly converged on just four
      types-mottled (irregular), scales, bars and spots (regular)-and habitat could be
      driving convergent evolution in avian patterning. Based on sensory ecology, we
      therefore predict that irregular patterns would be associated with visually noisy
      closed habitats and that regular patterns would be associated with open habitats.
      Regular patterns have also been shown to function in communication for sexually
      competing males to stand-out and attract females, so we predict that male
      breeding plumage patterns evolved in both open and closed habitats. Here, taking
      phylogenetic relatedness into account, we investigate ecological selection for
      bird plumage patterns across the class Aves. We surveyed plumage patterns in 80%
      of all avian species worldwide. Of these, 2,756 bird species have regular and
      irregular plumage patterns as well as habitat information. In this subset, we
      tested whether adult breeding/non-breeding plumages in each sex, and juvenile
      plumages, were associated with the habitat types found within the species'
      geographical distributions. We found no evidence for an association between
      habitat and plumage patterns across the world's birds and little phylogenetic
      signal. We also found that species with regular and irregular plumage patterns
      were distributed randomly across the world's eco-regions without being affected
      by habitat type. These results indicate that at the global spatial and taxonomic
      scale, habitat does not predict convergent evolution in bird plumage patterns,
      contrary to the camouflage hypothesis.

PMID- 27867763
TI  - Sexual reproduction in the Caribbean coral genus Isophyllia (Scleractinia:
      Mussidae).
AB  - The sexual pattern, reproductive mode, and timing of reproduction of Isophyllia
      sinuosa and Isophyllia rigida, two Caribbean Mussids, were assessed by
      histological analysis of specimens collected monthly during 2000-2001. Both
      species are simultaneous hermaphroditic brooders characterized by a single annual
      gametogenetic cycle. Spermatocytes and oocytes of different stages were found to
      develop within the same mesentery indicating sequential maturation for extended
      planulation. Oogenesis took place during May through April in I. sinuosa and from
      August through June in I. rigida. Oocytes began development 7-8 months prior to
      spermaries but both sexes matured simultaneously. Zooxanthellate planulae were
      observed in I. sinuosa during April and in I. rigida from June through September.
      Higher polyp and mesenterial fecundity were found in I. rigida compared to I.
      sinuosa. Larger oocyte sizes were found in I. sinuosa than in I. rigida, however
      larger planula sizes were found in I. rigida. Hermaphroditism is the exclusive
      sexual pattern within the Mussidae while brooding has been documented within the
      related genera Mussa, Scolymia and Mycetophyllia. This study represents the first
      description of the sexual characteristics of I. rigida and provides an updated
      description of I. sinuosa.

PMID- 27867764
TI  - Low self-concept in poor readers: prevalence, heterogeneity, and risk.
AB  - There is evidence that poor readers are at increased risk for various types of
      low self-concept-particularly academic self-concept. However, this evidence
      ignores the heterogeneous nature of poor readers, and hence the likelihood that
      not all poor readers have low self-concept. The aim of this study was to better
      understand which types of poor readers have low self-concept. We tested 77
      children with poor reading for their age for four types of self-concept, four
      types of reading, three types of spoken language, and two types of attention. We
      found that poor readers with poor attention had low academic self-concept, while
      poor readers with poor spoken language had low general self-concept in addition
      to low academic self-concept. In contrast, poor readers with typical spoken
      language and attention did not have low self-concept of any type. We also
      discovered that academic self-concept was reliably associated with reading and
      receptive spoken vocabulary, and that general self-concept was reliably
      associated with spoken vocabulary. These outcomes suggest that poor readers with
      multiple impairments in reading, language, and attention are at higher risk for
      low academic and general self-concept, and hence need to be assessed for self
      concept in clinical practice. Our results also highlight the need for further
      investigation into the heterogeneous nature of self-concept in poor readers.

PMID- 27867766
TI  - Reanalysis of the anthrax epidemic in Rhodesia, 1978-1984.
AB  - In the mid-1980s, the largest epidemic of anthrax of the last 200 years was
      documented in a little known series of studies by Davies in The Central African
      Journal of Medicine. This epidemic involved thousands of cattle and 10,738 human
      cases with 200 fatalities in Rhodesia during the Counterinsurgency. Grossly
      unusual epidemiological features were noted that, to this day, have not been
      definitively explained. This study performed a historical reanalysis of the data
      to reveal an estimated geographic involvement of 245,750 km2, with 171,990 cattle
      and 17,199 human cases. Here we present the first documented geotemporal
      visualization of the human anthrax epidemic.

PMID- 27867765
TI  - Charge neutralization as the major factor for the assembly of nucleocapsid-like
      particles from C-terminal truncated hepatitis C virus core protein.
AB  - BACKGROUND: Hepatitis C virus (HCV) core protein, in addition to its structural
      role to form the nucleocapsid assembly, plays a critical role in HCV pathogenesis
      by interfering in several cellular processes, including microRNA and mRNA
      homeostasis. The C-terminal truncated HCV core protein (C124) is intrinsically
      unstructured in solution and is able to interact with unspecific nucleic acids,
      in the micromolar range, and to assemble into nucleocapsid-like particles (NLPs)
      in vitro. The specificity and propensity of C124 to the assembly and its
      implications on HCV pathogenesis are not well understood. METHODS: Spectroscopic
      techniques, transmission electron microscopy and calorimetry were used to better
      understand the propensity of C124 to fold or to multimerize into NLPs when
      subjected to different conditions or in the presence of unspecific nucleic acids
      of equivalent size to cellular microRNAs. RESULTS: The structural analysis
      indicated that C124 has low propensity to self-folding. On the other hand, for
      the first time, we show that C124, in the absence of nucleic acids, multimerizes
      into empty NLPs when subjected to a pH close to its isoelectric point (pH ~ 12),
      indicating that assembly is mainly driven by charge neutralization. Isothermal
      calorimetry data showed that the assembly of NLPs promoted by nucleic acids is
      enthalpy driven. Additionally, data obtained from fluorescence correlation
      spectroscopy show that C124, in nanomolar range, was able to interact and to
      sequester a large number of short unspecific nucleic acids into NLPs. DISCUSSION:
      Together, our data showed that the charge neutralization is the major factor for
      the nucleocapsid-like particles assembly from C-terminal truncated HCV core
      protein. This finding suggests that HCV core protein may physically interact with
      unspecific cellular polyanions, which may correspond to microRNAs and mRNAs in a
      host cell infected by HCV, triggering their confinement into infectious
      particles.

PMID- 27867767
TI  - Factors influencing infection and transmission of Anopheles gambiae densovirus
      (AgDNV) in mosquitoes.
AB  - Anopheles gambiae densovirus (AgDNV) is a potential microbial agent for
      paratransgenesis and gene transduction in An. gambiae, the major vector of human
      malaria in sub-Saharan Africa. Understanding the interaction between AgDNV and
      An. gambiae is critical for using AgDNV in a basic and applied manner for
      Anopheles gene manipulation. Here, we tested the effects of mosquito age, sex,
      blood feeding status, and potential for horizontal transmission using an enhanced
      green fluorescent protein (EGFP) reporter AgDNV system. Neither mosquito age at
      infection nor feeding regime affected viral titers. Female mosquitoes were more
      permissive to viral infection than males. Despite low viral titers, infected
      males were able to venereally transmit virus to females during mating, where the
      virus was localized with the transferred sperm in the spermathecae. These
      findings will be useful for designing AgDNV-based strategies to manipulate
      Anopheles gambiae.

PMID- 27867768
TI  - Induced pluripotent stem cells from human hair follicle keratinocytes as a
      potential source for in vitro hair follicle cloning.
AB  - BACKGROUND: Human hair follicles are important for the renewal of new hairs and
      their development. The generation of induced pluripotent stem cells (iPSCs) from
      hair follicles is easy due to its accessibility and availability. The pluripotent
      cells derived from hair follicles not only have a higher tendency to re
      differentiate into hair follicles, but are also more suited for growth in hair
      scalp tissue microenvironment. METHODS: In this study, human hair follicular
      keratinocytes were used to generate iPSCs, which were then further differentiated
      in vitro into keratinocytes. The derived iPSCs were characterised by using
      immunofluorescence staining, flow cytometry, and reverse-transcription PCR to
      check for its pluripotency markers expression. RESULTS: The iPSC clones expressed
      pluripotency markers such as TRA-1-60, TRA-1-81, SSEA4, OCT4, SOX2, NANOG, LEFTY,
      and GABRB. The well-formed three germ layers were observed during differentiation
      using iPSCs derived from hair follicles. The successful formation of keratioctyes
      from iPSCs was confirmed by the expression of cytokeratin 14 marker. DISCUSSION:
      Hair follicles represent a valuable keratinocytes source for in vitro hair
      cloning for use in treating hair balding or grafting in burn patients. Our
      significant findings in this report proved that hair follicles could be used to
      produce pluripotent stem cells and suggested that the genetic and micro
      environmental elements of hair follicles might trigger higher and more efficient
      hair follicles re-differentiation.

PMID- 27867770
TI  - Soymilk residue (okara) as a natural immobilization carrier for Lactobacillus
      plantarum cells enhances soymilk fermentation, glucosidic isoflavone
      bioconversion, and cell survival under simulated gastric and intestinal
      conditions.
AB  - Cell immobilization is an alternative to microencapsulation for the maintenance
      of cells in a liquid medium. However, artificial immobilization carriers are
      expensive and pose a high safety risk. Okara, a food-grade byproduct from soymilk
      production, is rich in prebiotics. Lactobacilli could provide health enhancing
      effects to the host. This study aimed to evaluate the potential of okara as a
      natural immobilizer for L. plantarum 70810 cells. The study also aimed to
      evaluate the effects of okara-immobilized L. plantarum 70810 cells (IL) on
      soymilk fermentation, glucosidic isoflavone bioconversion, and cell resistance to
      simulated gastric and intestinal stresses. Scanning electron microscopy (SEM) was
      used to show cells adherence to the surface of okara. Lactic acid, acetic acid
      and isoflavone analyses in unfermented and fermented soymilk were performed by
      HPLC with UV detection. Viability and growth kinetics of immobilized and free L.
      plantarum 70810 cells (FL) were followed during soymilk fermentation. Moreover,
      changes in pH, titrable acidity and viscosity were measured by conventional
      methods. For in vitro testing of simulated gastrointestinal resistance, fermented
      soymilk was inoculated with FL or IL and an aliquot incubated into acidic MRS
      broth which was conveniently prepared to simulate gastric, pancreatic juices and
      bile salts. Survival to simulated gastric and intestinal stresses was evaluated
      by plate count of colony forming units on MRS agar. SEM revealed that the
      lactobacilli cells attached and bound to the surface of okara. Compared with FL,
      IL exhibited a significantly higher specific growth rate, shorter lag phase of
      growth, higher productions of lactic and acetic acids, a faster decrease in pH
      and increase in titrable acidity, and a higher soymilk viscosity. Similarly, IL
      in soymilk showed higher productions of daizein and genistein compared with the
      control. Compared with FL, IL showed reinforced resistance to simulatedgastric
      and intestinal stresses in vitro that included low pH, low pH plus pepsin,
      pancreatin, and bile salt. Our results indicate that okara is a new potential
      immobilization carrier to enhance the growth and glucosidic isoflavone
      bioconversion activities of L. plantarum in soymilk and improve cell
      survivability following simulated gastric and intestinal conditions.

PMID- 27867769
TI  - Comparative analysis of the complete chloroplast genome sequences in psammophytic
      Haloxylon species (Amaranthaceae).
AB  - The Haloxylon genus belongs to the Amaranthaceae (formerly Chenopodiaceae)
      family. The small trees or shrubs in this genus are referred to as the King of
      psammophytic plants, and perform important functions in environmental protection,
      including wind control and sand fixation in deserts. To better understand these
      beneficial plants, we sequenced the chloroplast (cp) genomes of Haloxylon
      ammodendron (HA) and Haloxylon persicum (HP) and conducted comparative genomic
      analyses on these and two other representative Amaranthaceae species. Similar to
      other higher plants, we found that the Haloxylon cp genome is a quadripartite,
      double-stranded, circular DNA molecule of 151,570 bp in HA and 151,586 bp in HP.
      It contains a pair of inverted repeats (24,171 bp in HA and 24,177 bp in HP) that
      separate the genome into a large single copy region of 84,214 bp in HA and 84,217
      bp in HP, and a small single copy region of 19,014 bp in HA and 19,015 bp in HP.
      Each Haloxylon cp genome contains 112 genes, including 78 coding, 30 tRNA, and
      four ribosomal RNA genes. We detected 59 different simple sequence repeat loci,
      including 44 mono-nucleotide, three di-nucleotide, one tri-nucleotide, and 11
      tetra-nucleotide repeats. Comparative analysis revealed only 67 mutations between
      the two species, including 44 substitutions, 23 insertions/deletions, and two
      micro-inversions. The two inversions, with lengths of 14 and 3 bp, occur in the
      petA-psbJ intergenic region and rpl16 intron, respectively, and are predicted to
      form hairpin structures with repeat sequences of 27 and 19 bp, respectively, at
      the two ends. The ratio of transitions to transversions was 0.76. These results
      are valuable for future studies on Haloxylon genetic diversity and will enhance
      our understanding of the phylogenetic evolution of Amaranthaceae.

PMID- 27867773
TI  - Abstract: PRS PSRC Poster Proofs PSRC 2016.

PMID- 27867771
TI  - Prospect and progress of oncolytic viruses for treating peripheral nerve sheath
      tumors.
AB  - INTRODUCTION: Peripheral nerve sheath tumors (PNSTs) are an assorted group of
      neoplasms originating from neuroectoderm and growing in peripheral nerves.
      Malignant transformation leads to a poor prognosis and is often lethal. Current
      treatment of PNSTs is predominantly surgical, which is often incomplete or
      accompanied by significant loss of function, in conjunction with radiotherapy
      and/or chemotherapy, for which the benefits are inconclusive. Oncolytic viruses
      (OVs) efficiently kill tumor cells while remaining safe for normal tissues, and
      are a novel antitumor therapy for patients with PNSTs. AREAS COVERED: Because of
      the low efficacy of current treatments, new therapies for PNSTs are needed. Pre
      clinically, OVs have demonstrated efficacy in treating PNSTs and perineural tumor
      invasion, as well as safety. We will discuss the various PNSTs and their
      preclinical models, and the OVs being tested for their treatment, including
      oncolytic herpes simplex virus (HSV), adenovirus (Ad), and measles virus (MV).
      OVs can be 'armed' to express therapeutic transgenes or combined with other
      therapeutics to enhance their activity. EXPERT OPINION: Preclinical testing of
      OVs in PNST models has demonstrated their therapeutic potential and provided
      support for clinical translation. Clinical studies with other solid tumors have
      provided evidence that OVs are safe in patients and efficacious. The recent
      successful completion of a phase III clinical trial of oncolytic HSV paves the
      way for oncolytic virotherapy to enter clinical practice.

PMID- 27867774
TI  - Abstract: PRS AAPS Poster Proofs 2016.

PMID- 27867775
TI  - Abstract: PRS PSRC Podium Proofs 2016.

PMID- 27867776
TI  - Abstract: PRS AAPS Oral Proofs 2016.

PMID- 27867772
TI  - PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival.
AB  - Cancer is one of the leading causes of death in America, and there is an urgent
      need for new therapeutic approaches. The progesterone receptor membrane component
      1 (PGRMC1) is a cytoch-rome b5 related protein that binds heme and is associated
      with signaling, apoptotic suppression and autophagy. PGRMC1 is essential for
      tumor formation, invasion and metastasis, and is upregulated in breast, colon,
      lung and thyroid tumors. In the present study, we have analyzed PGRMC1 levels in
      over 600 tumor sections, including a larger cohort of lung tumors than in
      previous studies, and report the first clinical analysis of PGRMC1 levels in
      human oral cavity and ovarian tumors compared to corresponding nonmalignant
      tissues. PGRMC1 was highly expressed in lung and ovarian cancers and correlated
      with patient survival. PGRMC1 has been previously associated with drug
      resistance, a characteristic of cancer stem cells. The stem cell theory proposes
      that a subset of cancerous stem cells contribute to drug resistance and tumor
      maintenance, and PGRMC1 was detected in lung-tumor derived stem cells. Drug
      treatment with a PGRMC1 inhibitor, AG-205, triggered stem cell death whereas
      treatment with erlotinib and the ERK inhibitor, PD98059, did not, suggesting a
      specific role for PGRMC1 in cancer stem cell viability. Together, our data
      demonstrate PGRMC1 as a potential tumor biomarker across a variety of tumors, as
      well as a therapeutic target for cancer stem cells.

PMID- 27867777
TI  - Welcome Letter.

PMID- 27867778
TI  - AAPS and PSRC 2016 Abstract Supplement.

PMID- 27867779
TI  - Meter-scale spark X-ray spectrum statistics.
AB  - X-ray emission by sparks implies bremsstrahlung from a population of energetic
      electrons, but the details of this process remain a mystery. We present detailed
      statistical analysis of X-ray spectra detected by multiple detectors during
      sparks produced by 1 MV negative high-voltage pulses with 1 MUs risetime. With
      over 900 shots, we statistically analyze the signals, assuming that the
      distribution of spark X-ray fluence behaves as a power law and that the energy
      spectrum of X-rays detectable after traversing ~2 m of air and a thin aluminum
      shield is exponential. We then determine the parameters of those distributions by
      fitting cumulative distribution functions to the observations. The fit results
      match the observations very well if the mean of the exponential X-ray energy
      distribution is 86 +/- 7 keV and the spark X-ray fluence power law distribution
      has index -1.29 +/- 0.04 and spans at least 3 orders of magnitude in fluence.

PMID- 27867780
TI  - Observation of intrinsically bright terrestrial gamma ray flashes from the
      Mediterranean basin.
AB  - We present three terrestrial gamma ray flashes (TGFs) observed over the
      Mediterranean basin by the Reuven Ramaty High Energy Solar Spectroscope Imager
      (RHESSI) satellite. Since the occurrence of these events in the Mediterranean
      region is quite rare, the characterization of the events was optimized by
      combining different approaches in order to better define the cloud of origin. The
      TGFs on 7 November 2004 and 16 October 2006 came from clouds with cloud top
      higher than 10-12 km where often a strong penetration into the stratosphere is
      found. This kind of cloud is usually associated with heavy precipitation and
      intense lightning activity. Nevertheless, the analysis of the cloud type based on
      satellite retrievals shows that the TGF on 27 May 2004 was produced by an unusual
      shallow convection. This result appears to be supported by the model simulation
      of the particle distribution and phase in the upper troposphere. The TGF on 7
      November 2004 is among the brightest ever measured by RHESSI. The analysis of the
      energy spectrum of this event is consistent with a production altitude <=12 km,
      which is in the upper part of the cloud, as found by the meteorological analysis
      of the TGF-producing thunderstorm. This event must be unusually bright at the
      source in order to produce such a strong signal in RHESSI. We estimate that this
      TGF must contain ~3 * 1018 initial photons with energy >1 MeV. This is 1 order of
      magnitude brighter than earlier estimations of an average RHESSI TGF.

PMID- 27867781
TI  - CloudSat 2C-ICE product update with a new Ze parameterization in lidar-only
      region.
AB  - The CloudSat 2C-ICE data product is derived from a synergetic ice cloud retrieval
      algorithm that takes as input a combination of CloudSat radar reflectivity (Ze )
      and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation lidar
      attenuated backscatter profiles. The algorithm uses a variational method for
      retrieving profiles of visible extinction coefficient, ice water content, and ice
      particle effective radius in ice or mixed-phase clouds. Because of the nature of
      the measurements and to maintain consistency in the algorithm numerics, we choose
      to parameterize (with appropriately large specification of uncertainty) Ze and
      lidar attenuated backscatter in the regions of a cirrus layer where only the
      lidar provides data and where only the radar provides data, respectively. To
      improve the Ze parameterization in the lidar-only region, the relations among Ze
      , extinction, and temperature have been more thoroughly investigated using
      Atmospheric Radiation Measurement long-term millimeter cloud radar and Raman
      lidar measurements. This Ze parameterization provides a first-order estimation of
      Ze as a function extinction and temperature in the lidar-only regions of cirrus
      layers. The effects of this new parameterization have been evaluated for
      consistency using radiation closure methods where the radiative fluxes derived
      from retrieved cirrus profiles compare favorably with Clouds and the Earth's
      Radiant Energy System measurements. Results will be made publicly available for
      the entire CloudSat record (since 2006) in the most recent product release known
      as R05.

PMID- 27867782
TI  - Surface dimming by the 2013 Rim Fire simulated by a sectional aerosol model.
AB  - The Rim Fire of 2013, the third largest area burned by fire recorded in
      California history, is simulated by a climate model coupled with a size-resolved
      aerosol model. Modeled aerosol mass, number, and particle size distribution are
      within variability of data obtained from multiple-airborne in situ measurements.
      Simulations suggest that Rim Fire smoke may block 4-6% of sunlight energy
      reaching the surface, with a dimming efficiency around 120-150 W m-2 per unit
      aerosol optical depth in the midvisible at 13:00-15:00 local time.
      Underestimation of simulated smoke single scattering albedo at midvisible by 0.04
      suggests that the model overestimates either the particle size or the absorption
      due to black carbon. This study shows that exceptional events like the 2013 Rim
      Fire can be simulated by a climate model with 1 degrees  resolution with overall
      good skill, although that resolution is still not sufficient to resolve the smoke
      peak near the source region.

PMID- 27867783
TI  - Convective and large-scale mass flux profiles over tropical oceans determined
      from synergistic analysis of a suite of satellite observations.
AB  - A new, satellite-based methodology is developed to evaluate convective mass flux
      and large-scale total mass flux. To derive the convective mass flux, candidate
      profiles of in-cloud vertical velocity are first constructed with a simple plume
      model under the constraint of ambient sounding and then narrowed down to the
      solution that matches satellite-derived cloud top buoyancy. Meanwhile, the large
      scale total mass flux is provided separately from satellite soundings by a method
      developed previously. All satellite snapshots are sorted into a composite time
      series that delineates the evolution of a vigorous and organized convective
      system. Principal findings are the following. First, convective mass flux is
      modulated primarily by convective cloud cover, with the intensity of individual
      convection being less variable over time. Second, convective mass flux dominates
      the total mass flux only during the early hours of the convective evolution; as
      convective system matures, a residual mass flux builds up in the mass flux
      balance that is reminiscent of stratiform dynamics. The method developed in this
      study is expected to be of unique utility for future observational diagnosis of
      tropical convective dynamics and for evaluation of global climate model cumulus
      parameterizations in a global sense.

PMID- 27867784
TI  - On the sensitivity of the diurnal cycle in the Amazon to convective intensity.
AB  - Climate and reanalysis models contain large water and energy budget errors over
      tropical land related to the misrepresentation of diurnally forced moist
      convection. Motivated by recent work suggesting that the water and energy budget
      is influenced by the sensitivity of the convective diurnal cycle to atmospheric
      state, this study investigates the relationship between convective intensity, the
      convective diurnal cycle, and atmospheric state in a region of frequent
      convection-the Amazon. Daily, 3-hourly satellite observations of top of
      atmosphere (TOA) fluxes from Clouds and the Earth's Radiant Energy System Ed3a
      SYN1DEG and precipitation from Tropical Rainfall Measuring Mission 3B42 data sets
      are collocated with twice daily Integrated Global Radiosonde Archive observations
      from 2002 to 2012 and hourly flux tower observations. Percentiles of daily
      minimum outgoing longwave radiation are used to define convective intensity
      regimes. The results indicate a significant increase in the convective diurnal
      cycle amplitude with increased convective intensity. The TOA flux diurnal phase
      exhibits 1-3 h shifts with convective intensity, and precipitation phase is less
      sensitive. However, the timing of precipitation onset occurs 2-3 h earlier and
      the duration lasts 3-5 h longer on very convective compared to stable days. While
      statistically significant changes are found between morning atmospheric state and
      convective intensity, variations in upper and lower tropospheric humidity exhibit
      the strongest relationships with convective intensity and diurnal cycle
      characteristics. Lastly, convective available potential energy (CAPE) is found to
      vary with convective intensity but does not explain the variations in Amazonian
      convection, suggesting that a CAPE-based convective parameterization will not
      capture the observed behavior without incorporating the sensitivity of convection
      to column humidity.

PMID- 27867785
TI  - Lightning Mapping Array flash detection performance with variable receiver
      thresholds.
AB  - This study characterizes Lightning Mapping Array performance for networks that
      participated in the Deep Convective Clouds and Chemistry field program using new
      Monte Carlo and curvature matrix model simulations. These open-source simulation
      tools are readily adapted to real-time operations or detailed studies of
      performance. Each simulation accounted for receiver threshold and location, as
      well as a reference distribution of source powers and flash sizes based on
      thunderstorm observations and the mechanics of station triggering. Source and
      flash detection efficiency were combined with solution bias and variability to
      predict flash area distortion at long ranges. Location errors and detection
      efficiency were highly dependent on the station configuration and thresholds,
      especially at longer ranges, such that performance varied more than expected
      across different networks and with azimuth within networks. Error characteristics
      matched prior studies, which led to an increase in flash distortion with range.
      Predicted flash detection efficiency exceeded 95% within 100 km of all networks.

PMID- 27867786
TI  - Aerosol lidar observations of atmospheric mixing in Los Angeles: Climatology and
      implications for greenhouse gas observations.
AB  - Atmospheric observations of greenhouse gases provide essential information on
      sources and sinks of these key atmospheric constituents. To quantify fluxes from
      atmospheric observations, representation of transport-especially vertical mixing
      is a necessity and often a source of error. We report on remotely sensed profiles
      of vertical aerosol distribution taken over a 2 year period in Pasadena,
      California. Using an automated analysis system, we estimate daytime mixing layer
      depth, achieving high confidence in the afternoon maximum on 51% of days with
      profiles from a Sigma Space Mini Micropulse LiDAR (MiniMPL) and on 36% of days
      with a Vaisala CL51 ceilometer. We note that considering ceilometer data on a
      logarithmic scale, a standard method, introduces, an offset in mixing height
      retrievals. The mean afternoon maximum mixing height is 770 m Above Ground Level
      in summer and 670 m in winter, with significant day-to-day variance (within
      season sigma = 220m~30%). Taking advantage of the MiniMPL's portability, we
      demonstrate the feasibility of measuring the detailed horizontal structure of the
      mixing layer by automobile. We compare our observations to planetary boundary
      layer (PBL) heights from sonde launches, North American regional reanalysis
      (NARR), and a custom Weather Research and Forecasting (WRF) model developed for
      greenhouse gas (GHG) monitoring in Los Angeles. NARR and WRF PBL heights at
      Pasadena are both systematically higher than measured, NARR by 2.5 times; these
      biases will cause proportional errors in GHG flux estimates using modeled
      transport. We discuss how sustained lidar observations can be used to reduce flux
      inversion error by selecting suitable analysis periods, calibrating models, or
      characterizing bias for correction in post processing.

PMID- 27867787
TI  - Interannual variation of springtime biomass burning in Indochina: Regional
      differences, associated atmospheric dynamical changes, and downwind impacts.
AB  - During March and April, widespread burning occurs across farmlands in Indochina
      in preparation for planting at the monsoon onset. The resultant aerosols impact
      the air quality downwind. In this study, we investigate the climatic aspect of
      the interannual variation of springtime biomass burning in Indochina and its
      correlation with air quality at Mt. Lulin in Taiwan using long-term (2005-2015)
      satellite and global reanalysis data. Based on empirical orthogonal function
      (EOF) analysis, we find that the biomass burning activities vary with two
      geographical regions: northern Indochina (the primary EOF mode) and southern
      Indochina (the secondary EOF mode). We determine that the variation of biomass
      burning over northern Indochina is significantly related with the change in
      aerosol concentrations at Mt. Lulin. This occurs following the change in the so
      called India-Burma Trough in the lower and middle troposphere. When the India
      Burma Trough is intensified, a stronger northwesterly wind (to the west of the
      trough) transports the dryer air from higher latitude into northern Indochina,
      and this promotes local biomass burning activities. The increase in upward motion
      to the east of the intensified India-Burma Trough lifts the aerosols, which are
      transported toward Taiwan by the increased low-level westerly jet. Further
      diagnoses revealed the connection between the India-Burma Trough and the South
      Asian jet's wave train pattern as well as the previous winter's El Nino-Southern
      Oscillation phase. This information highlights the role of the India-Burma Trough
      in modulating northern Indochina biomass burning and possibly predicting aerosol
      transport to East Asia on the interannual time scale.

PMID- 27867788
TI  - The stratigraphy and evolution of lower Mount Sharp from spectral, morphological,
      and thermophysical orbital data sets.
AB  - We have developed a refined geologic map and stratigraphy for lower Mount Sharp
      using coordinated analyses of new spectral, thermophysical, and morphologic
      orbital data products. The Mount Sharp group consists of seven relatively planar
      units delineated by differences in texture, mineralogy, and thermophysical
      properties. These units are (1-3) three spatially adjacent units in the Murray
      formation which contain a variety of secondary phases and are distinguishable by
      thermal inertia and albedo differences, (4) a phyllosilicate-bearing unit, (5) a
      hematite-capped ridge unit, (6) a unit associated with material having a strongly
      sloped spectral signature at visible near-infrared wavelengths, and (7) a layered
      sulfate unit. The Siccar Point group consists of the Stimson formation and two
      additional units that unconformably overlie the Mount Sharp group. All Siccar
      Point group units are distinguished by higher thermal inertia values and record a
      period of substantial deposition and exhumation that followed the deposition and
      exhumation of the Mount Sharp group. Several spatially extensive silica deposits
      associated with veins and fractures show that late-stage silica enrichment within
      lower Mount Sharp was pervasive. At least two laterally extensive hematitic
      deposits are present at different stratigraphic intervals, and both are
      geometrically conformable with lower Mount Sharp strata. The occurrence of
      hematite at multiple stratigraphic horizons suggests redox interfaces were
      widespread in space and/or in time, and future measurements by the Mars Science
      Laboratory Curiosity rover will provide further insights into the depositional
      settings of these and other mineral phases.

PMID- 27867789
TI  - The phenology of Arctic Ocean surface warming.
AB  - In this work, we explore the seasonal relationships (i.e., the phenology) between
      sea ice retreat, sea surface temperature (SST), and atmospheric heat fluxes in
      the Pacific Sector of the Arctic Ocean, using satellite and reanalysis data. We
      find that where ice retreats early in most years, maximum summertime SSTs are
      usually warmer, relative to areas with later retreat. For any particular year, we
      find that anomalously early ice retreat generally leads to anomalously warm SSTs.
      However, this relationship is weak in the Chukchi Sea, where ocean advection
      plays a large role. It is also weak where retreat in a particular year happens
      earlier than usual, but still relatively late in the season, primarily because
      atmospheric heat fluxes are weak at that time. This result helps to explain the
      very different ocean warming responses found in two recent years with extreme ice
      retreat, 2007 and 2012. We also find that the timing of ice retreat impacts the
      date of maximum SST, owing to a change in the ocean surface buoyancy and momentum
      forcing that occurs in early August that we term the Late Summer Transition
      (LST). After the LST, enhanced mixing of the upper ocean leads to cooling of the
      ocean surface even while atmospheric heat fluxes are still weakly downward. Our
      results indicate that in the near-term, earlier ice retreat is likely to cause
      enhanced ocean surface warming in much of the Arctic Ocean, although not where
      ice retreat still occurs late in the season.

PMID- 27867790
TI  - Magma injection into a long-lived reservoir to explain geodetically measured
      uplift: Application to the 2007-2014 unrest episode at Laguna del Maule volcanic
      field, Chile.
AB  - Moving beyond the widely used kinematic models for the deformation sources, we
      present a new dynamic model to describe the process of injecting magma into an
      existing magma reservoir. To validate this model, we derive an analytical
      solution and compare its results to those calculated using the Finite Element
      Method. A Newtonian fluid characterized by its viscosity, density, and
      overpressure (relative to the lithostatic value) flows through a vertical
      conduit, intruding into a reservoir embedded in an elastic domain, leading to an
      increase in reservoir pressure and time-dependent surface deformation. We apply
      our injection model to Interferometric Synthetic Aperture Radar (InSAR) data from
      the ongoing unrest episode at Laguna del Maule (Chile) volcanic field that
      started in 2007. Using a grid search optimization, we minimize the misfit to the
      InSAR displacement data and vary the three parameters governing the analytical
      solution: the characteristic timescale tauP for magma propagation, the maximum
      injection pressure, and the inflection time when the acceleration switches from
      positive to negative. For a spheroid with semimajor axis a = 6200 m, semiminor
      axis c = 100 m, located at a depth of 4.5 km in a purely elastic half-space, the
      best fit to the InSAR displacement data occurs for tauP =9.5 years and an
      injection pressure rising up to 11.5 MPa for 2 years. The volume flow rate
      increased to 1.2 m3/s for 2 years and then decreased to 0.7 m3/s in 2014. In 7.3
      years, at least 187 * 106 m3 of magma was injected.

PMID- 27867791
TI  - An assessment of forward and inverse GIA solutions for Antarctica.
AB  - In this work we assess the most recent estimates of glacial isostatic adjustment
      (GIA) for Antarctica, including those from both forward and inverse methods. The
      assessment is based on a comparison of the estimated uplift rates with a set of
      elastic-corrected GPS vertical velocities. These have been observed from an
      extensive GPS network and computed using data over the period 2009-2014. We find
      systematic underestimations of the observed uplift rates in both inverse and
      forward methods over specific regions of Antarctica characterized by low mantle
      viscosities and thin lithosphere, such as the northern Antarctic Peninsula and
      the Amundsen Sea Embayment, where its recent ice discharge history is likely to
      be playing a role in current GIA. Uplift estimates for regions where many GIA
      models have traditionally placed their uplift maxima, such as the margins of
      Filchner-Ronne and Ross ice shelves, are found to be overestimated. GIA estimates
      show large variability over the interior of East Antarctica which results in
      increased uncertainties on the ice-sheet mass balance derived from gravimetry
      methods.

PMID- 27867792
TI  - Statistical characterization of the growth and spatial scales of the substorm
      onset arc.
AB  - We present the first multievent study of the spatial and temporal structuring of
      the aurora to provide statistical evidence of the near-Earth plasma instability
      which causes the substorm onset arc. Using data from ground-based auroral
      imagers, we study repeatable signatures of along-arc auroral beads, which are
      thought to represent the ionospheric projection of magnetospheric instability in
      the near-Earth plasma sheet. We show that the growth and spatial scales of these
      wave-like fluctuations are similar across multiple events, indicating that each
      sudden auroral brightening has a common explanation. We find statistically that
      growth rates for auroral beads peak at low wave number with the most unstable
      spatial scales mapping to an azimuthal wavelength lambda~ 1700-2500 km in the
      equatorial magnetosphere at around 9-12 RE . We compare growth rates and spatial
      scales with a range of theoretical predictions of magnetotail instabilities,
      including the Cross-Field Current Instability and the Shear Flow Ballooning
      Instability. We conclude that, although the Cross-Field Current instability can
      generate similar magnitude of growth rates, the range of unstable wave numbers
      indicates that the Shear Flow Ballooning Instability is the most likely
      explanation for our observations.

PMID- 27867793
TI  - Internally driven large-scale changes in the size of Saturn's magnetosphere.
AB  - Saturn's magnetic field acts as an obstacle to solar wind flow, deflecting plasma
      around the planet and forming a cavity known as the magnetosphere. The
      magnetopause defines the boundary between the planetary and solar dominated
      regimes, and so is strongly influenced by the variable nature of pressure sources
      both outside and within. Following from Pilkington et al. (2014), crossings of
      the magnetopause are identified using 7 years of magnetic field and particle data
      from the Cassini spacecraft and providing unprecedented spatial coverage of the
      magnetopause boundary. These observations reveal a dynamical interaction where,
      in addition to the external influence of the solar wind dynamic pressure,
      internal drivers, and hot plasma dynamics in particular can take almost complete
      control of the system's dayside shape and size, essentially defying the solar
      wind conditions. The magnetopause can move by up to 10-15 planetary radii at
      constant solar wind dynamic pressure, corresponding to relatively "plasma-loaded"
      or "plasma-depleted" states, defined in terms of the internal suprathermal plasma
      pressure.

PMID- 27867794
TI  - The impact of an ICME on the Jovian X-ray aurora.
AB  - We report the first Jupiter X-ray observations planned to coincide with an
      interplanetary coronal mass ejection (ICME). At the predicted ICME arrival time,
      we observed a factor of ~8 enhancement in Jupiter's X-ray aurora. Within 1.5 h of
      this enhancement, intense bursts of non-Io decametric radio emission occurred.
      Spatial, spectral, and temporal characteristics also varied between ICME arrival
      and another X-ray observation two days later. Gladstone et al. (2002) discovered
      the polar X-ray hot spot and found it pulsed with 45 min quasiperiodicity. During
      the ICME arrival, the hot spot expanded and exhibited two periods: 26 min
      periodicity from sulfur ions and 12 min periodicity from a mixture of
      carbon/sulfur and oxygen ions. After the ICME, the dominant period became 42 min.
      By comparing Vogt et al. (2011) Jovian mapping models with spectral analysis, we
      found that during ICME arrival at least two distinct ion populations, from
      Jupiter's dayside, produced the X-ray aurora. Auroras mapping to magnetospheric
      field lines between 50 and 70 RJ were dominated by emission from precipitating
      sulfur ions (S7+,...,14+). Emissions mapping to closed field lines between 70 and
      120 RJ and to open field lines were generated by a mixture of precipitating
      oxygen (O7+,8+) and sulfur/carbon ions, possibly implying some solar wind
      precipitation. We suggest that the best explanation for the X-ray hot spot is
      pulsed dayside reconnection perturbing magnetospheric downward currents, as
      proposed by Bunce et al. (2004). The auroral enhancement has different spectral,
      spatial, and temporal characteristics to the hot spot. By analyzing these
      characteristics and coincident radio emissions, we propose that the enhancement
      is driven directly by the ICME through Jovian magnetosphere compression and/or a
      large-scale dayside reconnection event.

PMID- 27867795
TI  - Magnetic reconnection in Saturn's magnetotail: A comprehensive magnetic field
      survey.
AB  - Reconnection within planetary magnetotails is responsible for locally energizing
      particles and changing the magnetic topology. Its role in terms of global
      magnetospheric dynamics can involve changing the mass and flux content of the
      magnetosphere. We have identified reconnection related events in spacecraft
      magnetometer data recorded during Cassini's exploration of Saturn's magnetotail.
      The events are identified from deflections in the north-south component of the
      magnetic field, significant above a background level. Data were selected to
      provide full tail coverage, encompassing the dawn and dusk flanks as well as the
      deepest midnight orbits. Overall 2094 reconnection related events were
      identified, with an average rate of 5.0 events per day. The majority of events
      occur in clusters (within 3 h of other events). We examine changes in this rate
      in terms of local time and latitude coverage, taking seasonal effects into
      account. The observed reconnection rate peaks postmidnight with more infrequent
      but steady loss seen on the dusk flank. We estimate the mass loss from the event
      catalog and find it to be insufficient to balance the input from the moon
      Enceladus. Several reasons for this discrepancy are discussed. The reconnection X
      line location appears to be highly variable, though a statistical separation
      between events tailward and planetward of the X line is observed at a radial
      distance of between 20 and 30RS downtail. The small sample size at dawn prevents
      comprehensive statistical comparison with the dusk flank observations in terms of
      flux closure.

PMID- 27867797
TI  - Source of the dayside cusp aurora.
AB  - Monochromatic all-sky imagers at South Pole and other Antarctic stations of the
      Automatic Geophysical Observatory chain recorded the aurora in the region where
      the Time History of Events and Macroscale Interactions during Substorms (THEMIS)
      satellites crossed the dayside magnetopause. In several cases the magnetic field
      lines threading the satellites when mapped to the atmosphere were inside the
      imagers' field of view. From the THEMIS magnetic field and the plasma density
      measurements, we were able to locate the position of the magnetopause crossings
      and map it to the ionosphere using the Tsyganenko-96 field model. Field line
      mapping is reasonably accurate on the dayside subsolar region where the field is
      strong, almost dipolar even though compressed. From these coordinated
      observations, we were able to prove that the dayside cusp aurora of high 630 nm
      brightness is on open field lines, and it is therefore direct precipitation from
      the magnetosheath. The cusp aurora contained significant highly structured N2+
      427.8 nm emission. The THEMIS measurements of the magnetosheath particle energy
      and density taken just outside the magnetopause compared to the intensity of the
      structured N2+ 427.8 nm emissions showed that the precipitating magnetosheath
      particles had to be accelerated. The most likely electron acceleration mechanism
      is by dispersive Alfven waves propagating along the field line. Wave-accelerated
      suprathermal electrons were seen by FAST and DMSP. The 427.8 nm wavelength
      channel also shows the presence of a lower latitude hard-electron precipitation
      zone originating inside the magnetosphere.

PMID- 27867796
TI  - Highly relativistic radiation belt electron acceleration, transport, and loss:
      Large solar storm events of March and June 2015.
AB  - Two of the largest geomagnetic storms of the last decade were witnessed in 2015.
      On 17 March 2015, a coronal mass ejection-driven event occurred with a Dst (storm
      time ring current index) value reaching -223 nT. On 22 June 2015 another strong
      storm (Dst reaching -204 nT) was recorded. These two storms each produced almost
      total loss of radiation belt high-energy (E ? 1 MeV) electron fluxes. Following
      the dropouts of radiation belt fluxes there were complex and rather remarkable
      recoveries of the electrons extending up to nearly 10 MeV in kinetic energy. The
      energized outer zone electrons showed a rich variety of pitch angle features
      including strong "butterfly" distributions with deep minima in flux at alpha = 90
      degrees . However, despite strong driving of outer zone earthward radial
      diffusion in these storms, the previously reported "impenetrable barrier" at L ~
      2.8 was pushed inward, but not significantly breached, and no E ? 2.0 MeV
      electrons were seen to pass through the radiation belt slot region to reach the
      inner Van Allen zone. Overall, these intense storms show a wealth of novel
      features of acceleration, transport, and loss that are demonstrated in the
      present detailed analysis.

PMID- 27867798
TI  - Accurately characterizing the importance of wave-particle interactions in
      radiation belt dynamics: The pitfalls of statistical wave representations.
AB  - Wave-particle interactions play a crucial role in energetic particle dynamics in
      the Earth's radiation belts. However, the relative importance of different wave
      modes in these dynamics is poorly understood. Typically, this is assessed during
      geomagnetic storms using statistically averaged empirical wave models as a
      function of geomagnetic activity in advanced radiation belt simulations. However,
      statistical averages poorly characterize extreme events such as geomagnetic
      storms in that storm-time ultralow frequency wave power is typically larger than
      that derived over a solar cycle and Kp is a poor proxy for storm-time wave power.

PMID- 27867799
TI  - The "Puck" energetic charged particle detector: Design, heritage, and
      advancements.
AB  - Energetic charged particle detectors characterize a portion of the plasma
      distribution function that plays critical roles in some physical processes, from
      carrying the currents in planetary ring currents to weathering the surfaces of
      planetary objects. For several low-resource missions in the past, the need was
      recognized for a low-resource but highly capable, mass-species-discriminating
      energetic particle sensor that could also obtain angular distributions without
      motors or mechanical articulation. This need led to the development of a compact
      Energetic Particle Detector (EPD), known as the "Puck" EPD (short for hockey
      puck), that is capable of determining the flux, angular distribution, and
      composition of incident ions between an energy range of ~10 keV to several MeV.
      This sensor makes simultaneous angular measurements of electron fluxes from the
      tens of keV to about 1 MeV. The same measurements can be extended down to
      approximately 1 keV/nucleon, with some composition ambiguity. These sensors have
      a proven flight heritage record that includes missions such as MErcury Surface,
      Space ENvironment, GEochemistry, and Ranging and New Horizons, with multiple
      sensors on each of Juno, Van Allen Probes, and Magnetospheric Multiscale. In this
      review paper we discuss the Puck EPD design, its heritage, unexpected results
      from these past missions and future advancements. We also discuss high-voltage
      anomalies that are thought to be associated with the use of curved foils, which
      is a new foil manufacturing processes utilized on recent Puck EPD designs.
      Finally, we discuss the important role Puck EPDs can potentially play in upcoming
      missions.

PMID- 27867800
TI  - The Low-Energy Neutral Imager (LENI).
AB  - To achieve breakthroughs in the areas of heliospheric and magnetospheric
      energetic neutral atom (ENA) imaging, a new class of instruments is required. We
      present a high angular resolution ENA imager concept aimed at the suprathermal
      plasma populations with energies between 0.5 and 20 keV. This instrument is
      intended for understanding the spatial and temporal structure of the heliospheric
      boundary recently revealed by Interstellar Boundary Explorer instrumentation and
      the Cassini Ion and Neutral Camera. The instrument is also well suited to
      characterize magnetospheric ENA emissions from low-altitude ENA emissions
      produced by precipitation of magnetospheric ions into the terrestrial upper
      atmosphere, or from the magnetosheath where solar wind protons are neutralized by
      charge exchange, or from portions of the ring current region. We present a new
      technique utilizing ultrathin carbon foils, 2-D collimation, and a novel electron
      optical design to produce high angular resolution (<=2 degrees ) and high
      sensitivity (>=10-3 cm2 sr/pixel) ENA imaging in the 0.5-20 keV energy range.

PMID- 27867801
TI  - RAM-SCB simulations of electron transport and plasma wave scattering during the
      October 2012 "double-dip" storm.
AB  - Mechanisms for electron injection, trapping, and loss in the near-Earth space
      environment are investigated during the October 2012 "double-dip" storm using our
      ring current-atmosphere interactions model with self-consistent magnetic field
      (RAM-SCB). Pitch angle and energy scattering are included for the first time in
      RAM-SCB using L and magnetic local time (MLT)-dependent event-specific chorus
      wave models inferred from NOAA Polar-orbiting Operational Environmental
      Satellites (POES) and Van Allen Probes Electric and Magnetic Field Instrument
      Suite and Integrated Science observations. The dynamics of the source
      (approximately tens of keV) and seed (approximately hundreds of keV) populations
      of the radiation belts simulated with RAM-SCB is compared with Van Allen Probes
      Magnetic Electron Ion Spectrometer observations in the morning sector and with
      measurements from NOAA 15 satellite in the predawn and afternoon MLT sectors. We
      find that although the low-energy (E< 100 keV) electron fluxes are in good
      agreement with observations, increasing significantly by magnetospheric
      convection during both SYM-H dips while decreasing during the intermediate
      recovery phase, the injection of high-energy electrons is underestimated by this
      mechanism throughout the storm. Local acceleration by chorus waves intensifies
      the electron fluxes at E>=50 keV considerably, and RAM-SCB simulations
      overestimate the observed trapped fluxes by more than an order of magnitude; the
      precipitating fluxes simulated with RAM-SCB are weaker, and their temporal and
      spatial evolutions agree well with POES/Medium Energy Proton and Electron
      Detectors data.

PMID- 27867803
TI  - Effect of Bifidobacterium animalis ssp. lactis GCL2505 on visceral fat
      accumulation in healthy Japanese adults: a randomized controlled trial.
AB  - Bifidobacterium animalis ssp. lactis GCL2505 (B. lactis GCL2505) is able to
      survive passage through the intestine and then proliferate, leading to an
      increase in the amount of gut bifidobacteria. In the present study, we evaluated
      the impact of B. lactis GCL2505 on abdominal visceral fat storage in overweight
      and mildly obese Japanese adults. This clinical study was a double-blind,
      randomized, placebo-controlled, parallel-group comparative trial performed for 12
      weeks. Healthy Japanese subjects (N=137) with body mass indices ranging from 23
      to 30 kg/m2 consumed either fermented milk containing B. lactis GCL2505 or a
      placebo every day, and then visceral and subcutaneous abdominal fat areas were
      measured by computed tomography as the primary endpoints. The number of fecal
      bifidobacteria was also measured. Visceral fat area, but not subcutaneous fat
      area, was significantly reduced from baseline at 8 and 12 weeks in the GCL2505
      group, compared with the placebo group. The total number of fecal bifidobacteria
      was significantly increased in the GCL2505 group. These results indicate that B.
      lactis GCL2505 reduces abdominal visceral fat, a key factor associated with
      metabolic disorders. This finding suggests that this probiotic strain can
      potentially serve as a specific functional food to achieve visceral fat reduction
      in overweight or mildly obese individuals.

PMID- 27867802
TI  - Structural diversity and biological significance of lipoteichoic acid in Gram
      positive bacteria: focusing on beneficial probiotic lactic acid bacteria.
AB  - Bacterial cell surface molecules are at the forefront of host-bacterium
      interactions. Teichoic acids are observed only in Gram-positive bacteria, and
      they are one of the main cell surface components. Teichoic acids play important
      physiological roles and contribute to the bacterial interaction with their host.
      In particular, lipoteichoic acid (LTA) anchored to the cell membrane has
      attracted attention as a host immunomodulator. Chemical and biological
      characteristics of LTA from various bacteria have been described. However, most
      of the information concerns pathogenic bacteria, and information on beneficial
      bacteria, including probiotic lactic acid bacteria, is insufficient. LTA is
      structurally diverse. Strain-level structural diversity of LTA is suggested to
      underpin its immunomodulatory activities. Thus, the structural information on LTA
      in probiotics, in particular strain-associated diversity, is important for
      understanding its beneficial roles associated with the modulation of immune
      response. Continued accumulation of structural information is necessary to
      elucidate the detailed physiological roles and significance of LTA. In this
      review article, we summarize the current state of knowledge on LTA structure, in
      particular the structure of LTA from lactic acid bacteria. We also describe the
      significance of structural diversity and biological roles of LTA.

PMID- 27867804
TI  - DFAST and DAGA: web-based integrated genome annotation tools and resources.
AB  - Quality assurance and correct taxonomic affiliation of data submitted to public
      sequence databases have been an everlasting problem. The DDBJ Fast Annotation and
      Submission Tool (DFAST) is a newly developed genome annotation pipeline with
      quality and taxonomy assessment tools. To enable annotation of ready-to-submit
      quality, we also constructed curated reference protein databases tailored for
      lactic acid bacteria. DFAST was developed so that all the procedures required for
      DDBJ submission could be done seamlessly online. The online workspace would be
      especially useful for users not familiar with bioinformatics skills. In addition,
      we have developed a genome repository, DFAST Archive of Genome Annotation (DAGA),
      which currently includes 1,421 genomes covering 179 species and 18 subspecies of
      two genera, Lactobacillus and Pediococcus, obtained from both DDBJ/ENA/GenBank
      and Sequence Read Archive (SRA). All the genomes deposited in DAGA were annotated
      consistently and assessed using DFAST. To assess the taxonomic position based on
      genomic sequence information, we used the average nucleotide identity (ANI),
      which showed high discriminative power to determine whether two given genomes
      belong to the same species. We corrected mislabeled or misidentified genomes in
      the public database and deposited the curated information in DAGA. The repository
      will improve the accessibility and reusability of genome resources for lactic
      acid bacteria. By exploiting the data deposited in DAGA, we found intraspecific
      subgroups in Lactobacillus gasseri and Lactobacillus jensenii, whose variation
      between subgroups is larger than the well-accepted ANI threshold of 95% to
      differentiate species. DFAST and DAGA are freely accessible at
      https://dfast.nig.ac.jp.

PMID- 27867805
TI  - Isolation of lactic acid bacteria bound to the porcine intestinal mucosa and an
      analysis of their moonlighting adhesins.
AB  - The adhesion of lactic acid bacteria (LAB) to the intestinal mucosa is one of the
      criteria in selecting for probiotics. Eighteen LAB were isolated from porcine
      intestinal mucin (PIM): ten strains of Lactobacillus, six strains of Weissella,
      and two strains of Streptococcus. Using sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) for phosphate-buffered saline (PBS) extracts from the
      LAB, many bands were detected in half of the samples, while a few and/or no clear
      bands were detected in the other half. All six of the selected LAB showed
      adhesion to PIM. L. johnsonii MYU 214 and MYU 221 showed adhesion at more than
      10%. W. viridescens MYU 208, L. reuteri MYU 213, L. mucosae MYU 225, and L.
      agilis MYU 227 showed medium levels of adhesion at 5.9-8.3%. In a comprehensive
      analysis for the adhesins in the PBS extracts using a receptor overlay analysis,
      many moonlighting proteins were detected and identified as candidates for
      adhesins: GroEL, enolase, and elongation factor Tu in MYU 208; peptidase C1,
      enolase, formyl-CoA transferase, phosphoglyceromutase, triosephosphate isomerase,
      and phosphofructokinase in MYU 221; and DnaK, enolase, and phosphoglycerate
      kinase in MYU 227. These proteins in the PBS extracts, which included such things
      as molecular chaperones and glycolytic enzymes, may play important roles as
      adhesins.

PMID- 27867806
TI  - Bile metabolites of polycyclic aromatic hydrocarbons (PAHs) in three species of
      fish from Morocco.
AB  - BACKGROUND: Polycyclic aromatic hydrocarbons (PAH) are environmental contaminants
      that pose significant risk to health of fish. Environmental pollution of fish is
      a topic of rising attention in Morocco. However, only few studies have been
      carried out so far, describing the potential threat of organic pollution to
      Moroccan aquatic ecosystem. Two polycyclic aromatic hydrocarbon (PAH)
      metabolites, 1-hydroxypyrene (1-OH-Pyr) and 1-hydroxyphenanthrene (1-OH-Phen),
      were identified and quantified from the bile of 18 European eels (Anguilla
      anguilla), 7 Moray (Muraenidae), and 28 Conger eels (Conger conger) collected
      from Moulay Bousselham lagoon and Boujdour coast. The bile metabolites were
      separated by high-performance liquid chromatography with fluorescence detection.
      The present study aims to compare the levels of PAH metabolites in fish from the
      lagoon and the open sea and to compare levels of PAH metabolites in different
      fish species. RESULTS: The major metabolite present in all fish was 1
      hydroxypyrene (<LOD-15.56 ng/mL) with lower concentration of 1
      hydroxyphenanthrene (<LOD-9.6 ng/mL). These concentrations of PAH metabolites are
      low compared to studies published before. CONCLUSION: The data confirm the
      importance of 1-hydroxypyrene as the key PAH metabolite in fish bile and suggest
      that the European eel is an ideal species for monitoring PAHs in Moroccan waters.
      The present study provides valuable information on concentrations of PAH
      metabolites in fish from Morocco, especially for the first time for Conger eels
      and Moray.

PMID- 27867808
TI  - Magnetohydrodynamics flow of a nanofluid driven by a stretching/shrinking sheet
      with suction.
AB  - The present paper investigates the effect of a mathematical model describing the
      aforementioned process in which the ambient nanofluid in the presence of
      suction/injection and magnetic field are taken into consideration. The flow is
      induced by an infinite elastic sheet which is stretched along its own plane. The
      stretching/shrinking of the sheet is assumed to be proportional to the distance
      from the slit. The governing equations are reduced to a nonlinear ordinary
      differential equation by means of similarity transformation. The consequential
      nonlinear equation is solved analytically. Consequences show that the flow field
      can be divided into a near-field region and a far-field region. Suction on the
      surface plays an important role in the flow development in the near-field whereas
      the far-field is responsible mainly by stretching. The electromagnetic effect
      plays exactly the same role as the MHD, which is to reduce the horizontal flow
      resulting from stretching. It is shown that the behavior of the fluid flow
      changes with the change of the nanoparticles type. The present study throws light
      on the analytical solution of a class of laminar boundary layer equations arising
      in the stretching/shrinking sheet problem.

PMID- 27867807
TI  - Screening for potential endocrine disruptors in fish: evidence from structural
      alerts and in vitro and in vivo toxicological assays.
AB  - BACKGROUND: The European chemicals' legislation REACH aims to protect man and the
      environment from substances of very high concern (SVHC). Chemicals like endocrine
      disruptors (EDs) may be subject to authorization. Identification of (potential)
      EDs with regard to the environment is limited because specific experimental
      assessments are not standard requirements under REACH. Evidence is based on a
      combination of in vitro and in vivo experiments (if available), expert judgement,
      and structural analogy with known EDs. OBJECTIVES: The objectives of this study
      are to review and refine structural alerts for the indication of potential
      estrogenic and androgenic endocrine activities based on in vitro studies; to
      analyze in vivo mammalian long-term reproduction studies with regard to estrogen-
      and androgen-sensitive endpoints in order to identify potential indicators for
      endocrine activity with regard to the environment; to assess the consistency of
      potential estrogenic and androgenic endocrine activities based on in vitro assays
      and in vivo mammalian long-term reproduction studies and fish life-cycle tests;
      and to evaluate structural alerts, in vitro assays, and in vivo mammalian long
      term reproduction studies for the indication of potential estrogenic and
      androgenic endocrine disruptors in fish. RESULTS: Screening for potential
      endocrine activities in fish via estrogenic and androgenic modes of action based
      on structural alerts provides similar information as in vitro receptor-mediated
      assays. Additional evidence can be obtained from in vivo mammalian long-term
      reproduction studies. Conclusive confirmation is possible with fish life-cycle
      tests. Application of structural alerts to the more than 33,000 discrete organic
      compounds of the EINECS inventory indicated 3585 chemicals (approx. 11%) as
      potential candidates for estrogenic and androgenic effects that should be further
      investigated. Endocrine activities of the remaining substances cannot be
      excluded; however, because the structural alerts perform much better for
      substances with (very) high estrogenic and androgenic activities, there is
      reasonable probability that the most hazardous candidates have been identified.
      CONCLUSIONS: The combination of structural alerts, in vitro receptor-based
      assays, and in vivo mammalian studies may support the priority setting for
      further assessments of chemicals with potential environmental hazards due to
      estrogenic and androgenic activities.

PMID- 27867809
TI  - Fixation of split-thickness skin graft using fast-clotting fibrin glue containing
      undiluted high-concentration thrombin or sutures: a comparison study.
AB  - OBJECTIVE: For skin defects caused by full-thickness burns, trauma, or tumor
      tissue excision, skin grafting is one of the most convenient and useful treatment
      methods. In this situation, graft fixation is important in skin grafting. This
      study was performed to compare the effectiveness of skin graft fixation between
      high-concentration fibrin sealant and sutures. There have been numerous studies
      using fibrin sealant for graft fixation, but they utilized slow-clotting fibrin
      sealant containing less than 10 IU/mL thrombin. METHOD: Twenty-five patients
      underwent split-thickness skin grafting using fast-clotting fibrin sealant
      containing 400 IU/mL thrombin, while 30 patients underwent grafting using
      sutures. Rates of hematoma/seroma formation, graft dislocation, graft necrosis,
      and graft take were investigated postoperatively. The graft surface area was
      calculated using Image J software (National Institutes of Health, Bethesda, MD,
      USA). RESULT: After 5 days, rates of hematoma/seroma formation and graft
      dislocation were 7.84 and 1.29% in group I, and 9.55 and 1.45% in group II,
      respectively. After 30 days, rates of graft necrosis and graft take were 1.86 and
      98.14% in group I, and 4.65 and 95.35% in group II. Undiluted fibrin sealant
      showed significantly superior results for all rates (p < 0.05) except graft
      dislocation. CONCLUSION: When high-concentration fast-clotting fibrin sealant was
      applied to skin grafts without dilution, no difficulty was experienced during
      surgery. Sealant showed superior results compared with sutures and had an
      excellent graft take rate. LEVEL OF EVIDENCE: II.

PMID- 27867810
TI  - Bio-ethanol production from wet coffee processing waste in Ethiopia.
AB  - Large amounts of coffee residues are generated from coffee processing plants in
      Ethiopia. These residues are toxic and possess serious environmental problems
      following the direct discharge into the nearby water bodies which cause serious
      environmental and health problems. This study was aimed to quantify wet coffee
      processing waste and estimate its bio-ethanol production. The study showed that
      the wastes are potential environmental problems and cause water pollution due to
      high organic component and acidic nature. The waste was hydrolyzed by dilute
      H2SO4 (0.2, 0.4, 0.6, 0.8 and 1 M) and distilled water. Total sugar content of
      the sample was determined titrimetrically and refractometry. Maximum value (90%)
      was obtained from hydrolysis by 0.4 M H2SO4. Ethanol production was monitored by
      gas chromatography. The optimum yield of ethanol (78%) was obtained from the
      sample hydrolyzed by 0.4 M H2SO4 for 1 h at hydrolysis temperature of 100 
      degrees C and after fermentation for 24 h and initial pH of 4.5. Based on the
      data, it was concluded that reuse of the main coffee industry wastes is of
      significant importance from environmental and economical view points. In
      conclusion, this study has proposed to utilize the wet coffee processing waste to
      produce bio-ethanol which provides the alternative energy source from waste
      biomass and solves the environmental waste disposal as well as human health
      problem.

PMID- 27867811
TI  - Dramatic mitigation of bone pain after phosphorus replacement therapy in a
      subject with FGF23-related hypophosphatemic osteomalacia.
AB  - INTRODUCTION: Fibroblast growth factor 23 (FGF23) is secreted from bone and
      suppresses the absorption of phosphorus in renal proximal tubule and in
      intestinal tract. Therefore, the increase of serum FGF23 levels leads to
      hypophosphatemic situations. Tumor-induced osteomalacia is often induced by
      various tumors, but it is often difficult to identify the localization of tumor,
      because most of the FGF23-producing tumors are small and could be observed in any
      part of the body. CASE DESCRIPTION: Here we report a case of elderly female
      subject with FGF23-related hypophosphatemic osteomalacia who repeatedly
      experienced severe bone pain and fragility fracture in various parts of the body.
      Although we failed to identify the localization of tumor in this subject even
      with various examination, after starting phosphorus replacement therapy with
      relatively small amounts of calcium phosphate (1.5 g/day) (phosphorus content:
      270 mg), hypophosphatemia was ameliorated and repeated bone pain was dramatically
      mitigated without any surgical operation. DISCUSSION AND EVALUATION: Even when we
      fail to identify the localization of tumor in subjects with FGF23-related
      hypophosphatemic osteomalacia, phosphorus replacement therapy for
      hypophosphatemia could reduce the bone pain. CONCLUSIONS: We should be aware of
      the possibility that phosphorus replacement therapy exert marked beneficial
      effects for the reduction of bone pain in subjects with FGF23-related
      hypophosphatemic osteomalacia even when we fail to identify tumor localization.

PMID- 27867812
TI  - Comparisons of oncological and functional outcomes among radical retropubic
      prostatectomy, high dose rate brachytherapy, cryoablation and high-intensity
      focused ultrasound for localized prostate cancer.
AB  - PURPOSE: To conduct a retrospective, single institutional and comparative study
      for radical retropubic prostatectomy (RRP), high dose rate brachytherapy (HDRBT),
      cryoablation and high-intensity focused ultrasound (HIFU) in localized prostate
      cancer with respect to oncological and functional outcomes. METHODS: We reviewed
      97, 161, 114 and 120 patients of RRP, HDRBT, cryoablation and HIFU respectively
      for localized prostate cancer from May 2008 to December 2013. PSA biochemical
      recurrence, salvage treatment-free rate, metastasis-free rate, and biochemical
      recurrence-free survival were analyzed for oncological outcomes. Functional
      outcomes included complications and serial IIEF-5 scores, IPSS and related QoL
      scores. RESULTS: During nearly 3 years of follow-up, the patients of HDRBT
      experienced higher PSA biochemical recurrence rate overall (54.7%), as well as
      D'Amico intermediate-risk (34.4%) and high-risk (61.8%) groups, lower salvage
      treatment-free rate (46.7%), and metastasis-free rate (90.7%). Besides, the
      patients of RRP demonstrated higher urethral stricture (29.9%) and urinary
      incontinence (11.3%). The patients of HIFU revealed lower de novo erectile
      dysfunction rate at 1 year (65.6%), higher serial IIEF-5 scores, lower IPSS and
      related QoL scores. CONCLUSIONS: The patients of HDRBT demonstrated worse
      oncological outcomes in D'Amico intermediate and high-risk groups. Besides, the
      patients of RRP had more complications rate in urethral stricture and urinary
      incontinence. Moreover, the patients of HIFU experienced better urinary function
      improvement and more possible sexual function preservation. In consideration of
      trifecta, HIFU may provide equivalent cancer control and better quality of life
      for patients of localized prostate cancer.

PMID- 27867813
TI  - The evaluation of the three edible tissues of dead adult Chinese mitten crabs
      (Eriocheir sinensis) freshness in harvest season, based on the analysis of TVBN
      and biogenic amine.
AB  - This study was carried out to evaluate the quality of the three edible tissues
      (muscles, hepatopancreas and gonads) of the male and female Chinese mitten crab
      (Eriocheir sinensis) in natural harvest season, based on total volatile base
      nitrogen test (TVBN) and biogenic amines analysis at intervals time of 3 h
      extended for 24 h during 30  degrees C storage (a mean ambient temperature in
      harvest season). In addition, the relationship between the value of TVBN and
      storage time or main biogenic amine was evaluated. Results showed that TVBN level
      of female gonad reached the recommended limit (30 mg/100 g) at 3 h, and the times
      of reaching the recommended limit were 15 h in both sexes muscles, while in male
      and female hepatopancreas reached the recommended limit at times of over 24 and
      24 h respectively. Moreover, putrescine was highest in amount in all biogenic
      amines analyzed. We suggested that TVBN value could be as a good indicator for
      Chinese mitten crab freshness. According to analysis for biogenic amine
      accumulated in edible tissues of crab, it was possible that dead crab poisoning
      may be caused by putrescine. Dead Chinese mitten crabs for over 24 h, should be
      not recommended for eating or processing.

PMID- 27867814
TI  - The assessment of myometrium perfusion in patients with uterine fibroid by
      arterial spin labeling MRI.
AB  - BACKGROUND: It has been suggested that an inadequate blood supply caused by
      uterine fibroids may lead to decreasing fertility. Therefore, a quantitative
      evaluation of blood flow in the uterus might be a good tool for infertility
      treatments. For the first step, the ability to perform arterial spin labeling
      (ASL)-MRI in pelvic organs was examined by measuring blood flow in the uterine
      muscle layer. RESULTS: Three normal volunteer women, seven patients with one
      uterine fibroid and four patients treated with GnRH analogue for uterine
      fibroids, were enrolled in this study. Perfusion of normal uterine myometrium was
      examined using non-enhanced ASL-MRI. The region of interest was set in the
      uterine muscle layer, with a point in the iliopsoas or gluteus muscle. The ASL
      perfusion index was calculated as (ASL value in uterus-ASL value in
      iliopsoas/gluteus muscle). The ASL perfusion indexes in the secretory phase of
      all 3 volunteers were significantly lower than the indexes in the proliferative
      phases (P < 0.05). In patients with fibroids, all three types of fibroids
      (subserosal, intramural and submucosal types) were included. In seven patients
      harboring a single uterine fibroid, the ASL perfusion indexes of myometrium on
      the fibroid-positive side increased 4.9 fold compared with that of the fibroid
      negative side. With GnRH analogue treatment, ASL perfusion in myometrium
      decreased to 39% on average (P < 0.05). CONCLUSION: We utilized the ASL-MRI
      technique to evaluate perfusion of uterine myometrium. For clinical use, an
      inadequate blood supply caused by uterine fibroids is known to lead to decreasing
      fertility. The ASL-MRI technique might be useful to evaluate blood supply as a
      quantitative measurement of fertility in patients with uterine fibroids.

PMID- 27867815
TI  - Epitaxial growth of BaHfO3 buffer layer and its structure degeneration analysed
      by Raman spectrum.
AB  - BaHfO3 (BHO) has been proposed as a new cap layer material for YBa2Cu3O7-delta
      (YBCO) coated conductors. Highly c-axis oriented BHO cap layer has been deposited
      on ion-beam assisted deposition-MgO buffered Hastelloy tapes by direct-current
      magnetron sputtering method. The epi-growth of BHO films combined with its
      properties is investigated in details. The degenerated cubic crystal structure of
      BHO film is confirmed by Raman spectrum analysis. XRD theta-2theta scan, phi-scan
      and omega-scan reveal an excellent c-axis alignment with good in-plane and out-of
      plane textures for BHO cap layers. SEM and AFM investigations show BHO cap layer
      a dense and crack-free morphology. Subsequently pure c-axis orientation YBCO film
      was epitaxial grown on such BHO cap layer successfully, shown BaHfO3 a potential
      cap layer material for coated conductors.

PMID- 27867816
TI  - Severe ARDS caused by adenovirus: early initiation of ECMO plus continuous renal
      replacement therapy.
AB  - The reported survival rates of patients with acute respiratory distress syndrome
      (ARDS) caused by human adenovirus (HAdV) pneumonia are poor. The results do not
      differ much in immunocompetent patients supported by extracorporeal membrane
      oxygenation (ECMO). We report two immunocompetent patients with severe ARDS
      complicating HAdV pneumonia who were treated successfully and survived to
      discharge. Compared with previous cases, our cases might have benefited from
      several factors. First, the time interval between mechanical ventilator support
      and ECMO implantation was shorter. Second, we implemented conservative fluid
      management as recommended by the ARDS network using continuous renal replacement
      therapy (CRRT). Third, we administered an antiviral agent as early as possible. A
      clinical trial of early ECMO with CRRT and the administration of cidofovir in
      patients with severe ARDS complicating HAdV pneumonia are needed to confirm our
      results.

PMID- 27867817
TI  - Evaluating the enhancement and improvement of China's technology and financial
      services platform innovation strategy.
AB  - The development of high-tech industry has been prosperous around the world in
      past decades, while technology and finance have already become the most
      significant issues in the information era. While high-tech firms are a major
      force behind a country's economic development, it requires a lot of money for the
      development process, as well as the financing difficulties for its potential
      problems, thus, how to evaluate and establish appropriate technology and
      financial services platforms innovation strategy has become one of the most
      critical and difficult issues. Moreover, how the chosen intertwined financial
      environment can be optimized in order that high-tech firms financing problems can
      be decided has seldom been addressed. Thus, this research aims to establish a
      technology and financial services platform innovation strategy improvement model,
      as based on the hybrid MADM model, which addresses the main causal factors and
      amended priorities in order to strengthen ongoing planning. A DEMATEL technique,
      as based on Analytic Network Process, as well as modified VIKOR, will be proposed
      for selecting and re-configuring the aspired technology and financial services
      platform. An empirical study, as based on China's technology and financial
      services platform innovation strategy, will be provided for verifying the
      effectiveness of this proposed methodology. Based on expert interviews,
      technology and financial services platforms innovation strategy improvement
      should be made in the following order: credit guarantee platform (C)_credit
      rating platform (B)_investment and finance platform (A).

PMID- 27867818
TI  - A new gene regulatory network model based on BP algorithm for interrogating
      differentially expressed genes of Sea Urchin.
AB  - BACKGROUND: Computer science and mathematical theories are combined to analyze
      the complex interactions among genes, which are simplified to a network to
      establish a theoretical model for the analysis of the structure, module and
      dynamic properties. In contrast, traditional model of gene regulatory networks
      often lack an effective method for solving gene expression data because of high
      durational and spatial complexity. In this paper, we propose a new model for
      constructing gene regulatory networks using back propagation (BP) neural network
      based on predictive function and network topology. RESULTS: Combined with complex
      nonlinear mapping and self-learning, the BP neural network was mapped into a
      complex network. Network characteristics were obtained from the parameters of the
      average path length, average clustering coefficient, average degree, modularity,
      and map's density to simulate the real gene network by an artificial network.
      Through the statistical analysis and comparison of network parameters of Sea
      Urchin mRNA microarray data under different temperatures, the value of network
      parameters was observed. Differentially expressed Sea Urchin genes associated
      with temperature were determined by calculating the difference in the degree of
      each gene from different networks. CONCLUSION: The new model we developed is
      suitable to simulate gene regulatory network and has capability of determining
      differentially expressed genes.

PMID- 27867819
TI  - Assessment of genetic variability for grain nutrients from diverse regions:
      potential for wheat improvement.
AB  - BACKGROUND: A total of 150 bread wheat genotypes representing 121 Indian and 29
      Turkish origin were screened for nutrient concentrations and grain protein
      content. Elemental and grain protein composition were studied by Inductively
      Coupled Plasma-Atomic Emission Spectrophotometer and LECO analyser, respectively.
      The study was performed to determine the variability in nutrient concentrations
      present in the collected wheat genetic material from two countries. RESULTS:
      Several fold variations among genotypes existed for almost all the elements.
      Three major components of principal component analysis (PCA) revealed 60.8%
      variation among the genotypes. Nutrient variables segregated into two groups, one
      group containing all the macroelements except sulphur; and another cluster
      containing proteins and all the microelements except Zn and Mn. Pearson
      correlation analysis and heat-map were in accordance with each other determining
      strong positive association between P-K, Mn-Zn, Mg-S and Cu-protein content.
      Also, PCA and hierarchical grouping divided all the Indian and Turkish genotypes
      in two main clusters. CONCLUSIONS: Nutritional profile differentiated the
      genotypes from two countries into separate groups. However, some of the varieties
      were closely associated and indicated the success of global wheat exchange
      programs. While most of the correlations were in agreement with the previous
      studies, non-association of zinc with grain protein content directed towards its
      control by some other genetic factors. Some of the experimental wheat varieties
      with promising nutrient content have been suggested for future wheat advancement
      programs. Results obtained will be supportive for breeders involved in wheat
      biofortification programs, food industries and people relying on whole grain
      wheat products.

PMID- 27867820
TI  - Alteration of NPY in hypothalamus and its correlation with leptin and ghrelin
      during the development of T2DM in a rat model.
AB  - OBJECTIVES: This study aimed to investigate the alteration of Neuropeptide Y
      (NPY) in the hypothalamus and its correlation with insulin, leptin and ghrelin
      during the development of a rat model of type 2 diabetes mellitus. METHODS: The
      type 2 diabetes mellitus model was developed in diet-induced obesity (DIO) rats
      followed by the intraperitoneal injection of low-dose streptozotocin (STZ, 25
      mg/kg). At four time points during the development of type 2 diabetes mellitus in
      rats, the fasting serum insulin, leptin, and plasma ghrelin were measured and the
      hypothalamic neuropeptide Y (NPY) content and mRNA expression were detected in
      the rats, which were divided into 4 groups: normal control (NC), DIO4W, DIO8W,
      and T2DM; the mRNA expression of OB-Rb, and GSH-R1a in the hypothalamus were also
      assayed. RESULTS: During the development of the type 2 diabetes mellitus rat
      model, both the fasting serum levels of insulin and leptin (ng/ml) elevated
      significantly and the fasting plasma ghrelin concentration decreased the
      hypothalamic NPY (pg/mg) content significantly. NPY mRNA increased significantly
      in a time-dependent fashion while both the OB-Rb and the GHS-R1a mRNA of the
      hypothalamus decreased significantly. Hypothalamic NPY concentration was
      positively correlated with the changes in serum insulin and leptin and negatively
      correlated with plasma ghrelin. CONCLUSIONS: During the development of the type 2
      diabetes mellitus rat model, the hypothalamic NPY content and NPY mRNA expression
      increased in a time-dependent manner, which was positively correlated with the
      changes of the serum insulin and leptin and negatively correlated with the plasma
      ghrelin.

PMID- 27867821
TI  - Modified differential evolution algorithm with onlooker bee operator for mixed
      discrete-continuous optimization.
AB  - For solving non-linear programming problems containing discrete and continuous
      variables, this article suggests two modified algorithms based on differential
      evolution (DE). The two proposed algorithms incorporate a novel random search
      strategy into DE/best/1 and DE/cur-to-best/1 respectively. Inspired by the
      artificial bee colony algorithm, the random search strategy overcomes the
      searching unbalance of DE/best/1 and DE/cur-to-best/1 by enhancing the global
      exploration capability of promising individuals. Two numerical experiments are
      given to test the two modified algorithms. Experiment 1 is conducted on the
      benchmark function set of CEC2005 in order to verify the effectiveness of the
      improved strategy. Experiment 2 is designed to optimize two mixed discrete
      continuous problems to illustrate the competitiveness and the practicality of the
      proposed algorithms. In particular, the modified DE/cur-to-best/1 finds the new
      optima of two engineering optimization problems.

PMID- 27867822
TI  - Why do consumers respond to eco-labels? The case of Korea.
AB  - Although eco-labels were introduced with the intention of encouraging eco
      friendly purchasing behavior by consumers, they have had little effect on
      consumers' purchasing decisions, and therefore a significant gap exists between
      eco-label awareness and actual purchasing behavior. The aim of this study was to
      analyze consumer preference, in terms of public and private values, for two types
      of Korean eco-label that have been administered by the Korean government since
      1992. Analyses were based on a structural equation model, employing the theory of
      reasoned action. Data were collected by survey. The results indicate that
      although general consumers are highly aware of the publicly valuable information
      that eco-labels provide, privately valuable information exerts far greater power
      over their purchasing intentions. Therefore, a supplementary policy that converts
      public value to private value could promote the purchase of eco-labeled products.

PMID- 27867823
TI  - The burden of metastatic disease of the femur on the Medicare system.
AB  - BACKGROUND: In the United States, over 1,650,000 new cases of cancer are being
      diagnosed yearly with almost 50 % of them being the top five bone-seeking
      cancers. Since cancer risk increases with age, this suggests that orthopedic
      oncology services may be a strain on the Medicare system. The femur is the most
      common site of long bone metastases. Prophylactic fixation techniques prevent
      pathologic fractures, reduce morbidities, and enhance the quality of life of
      patients with femoral metastases. This study aims to assess the rate of
      metastatic disease to the skeleton and evaluate the use and financial burden of
      femoral prophylactic fixation techniques on the Medicare system.
      QUESTIONS/PURPOSES: (1) In the Medicare population, has the number of skeletal
      metastases increased? (2) In the Medicare population, has the use of prophylactic
      fixation techniques increased? (3) How has the financial burden of prophylactic
      fixation changed over the study period? METHODS: The Medicare database was
      searched between 2005 and 2014 with the assistance of PearlDiver Technologies
      Inc. and the RBRVS DataManager Online from the American Medical Association.
      Searches were completed by using International Classification of Disease-9 (ICD
      9) and current procedural terminology (CPT) codes for secondary malignant
      neoplasms and prophylactic fixation techniques. Facility charges, Medicare
      reimbursement and length of hospital stay were extracted from the Medicare
      database. Simple linear regression was performed to test the significance of
      yearly changes and the coefficient of determination was used to assess the
      strength of the correlation. RESULTS: (1) In the Medicare population, has the
      number of skeletal metastases increased? While the number of Medicare patients
      with skeletal metastases has increased from 132,452 in 2005 to 155,819 in 2012 (p
      = 0.01, r2 = 0.72), the prevalence of skeletal metastases in this population
      remained constant at 30.66 cases per 10,000 Medicare patients in 2012 (p = 0.56,
      r2 = 0.06). (2) In the Medicare population, has the use of prophylactic fixation
      techniques increased? The number of prophylactic fixation techniques has not
      increased from 2005 to 2014 (p = 0.68, r2 = 0.02); however, the rate of
      prophylactic fixation among those diagnosed with skeletal metastases has
      significantly decreased from 94.6 per 10,000 in 2005 to 82.72 per 10,000 in 2012
      (p = 0.006, r2 = 0.74). (3) How has the financial burden of prophylactic fixation
      changed over the study period? Both total and average hospital charges increased
      after adjusting for inflation in the total Medicare population; however, only the
      average Medicare reimbursement changed to reflect this. The total amount Medicare
      spent on prophylactic fixation techniques in 2012 was $20,245,957 after adjusting
      to 2014. Despite the increase in hospital charges and average Medicare
      reimbursement, the average length of hospital stay in the total Medicare
      population showed a significant decreased trend-down from 7.51 days in 2005 to
      5.86 days in 2012 (p = 0.02, r2 = 0.81). CONCLUSIONS: Although the prevalence of
      metastatic disease to the skeleton remained stable between 2005 and 2012 in the
      Medicare population, prophylactic femoral fixation techniques declined in elderly
      adults between 2005 and 2014. This most likely signifies an increase in other
      treatment modalities that can prevent pathologic fractures such as prophylactic
      hemiarthroplasty, bisphosphonates, and/or radiation therapy. LEVEL OF EVIDENCE:
      Level IV, Cross-sectional Study.

PMID- 27867824
TI  - Safety of heparin bridging therapy for transrectal ultrasound-guided prostate
      biopsy in patients requiring temporary discontinuation of antithrombotic agents.
AB  - BACKGROUND: Safety of heparin bridging therapy for transrectal ultrasound-guided
      prostate (TRUS) biopsy in patients requiring temporary discontinuation of
      antithrombotic therapy is unknown. This study aimed to assess the relationship
      between heparin bridging therapy and the incidence of complications after TRUS
      biopsy. METHODS: From January 2005 to November 2015, we performed 1307
      consecutive TRUS biopsies on 1134 patients in our hospital. The patients were
      assigned to two groups: those without heparin bridging (the control group) and
      those with temporary discontinuation of antithrombotic agents with heparin
      bridging therapy (the bridging group). A 10-12-core TRUS biopsy was performed;
      the patients were evaluated for bleeding-related complications. RESULTS: Of 1134
      patients, 1109 (1281 biopsies) and 25 (26 biopsies) were assigned to the control
      and bridging group, respectively. Patient background did not significantly differ
      between the control and bridging groups, except for age, history of diabetes,
      cardiovascular diseases, and CHADS2 scores. Compared with the control group, the
      bridging group showed a significantly higher rate of complication for any
      complication (35 vs. 8.3%, P < 0.001), bleeding-related complications (27 vs.
      4.4%), and urinary tract infection (7.7 vs. 1.2%). No thromboembolic event was
      observed in the present study. Multivariate logistic analysis showed that heparin
      bridging therapy was a significant risk factor for the incidence of any
      complication and bleeding-related complications. CONCLUSIONS: Heparin bridging
      therapy with temporal discontinuation of antithrombotic agents may increase the
      risk of complications after TRUS biopsy. Further, large-scale studies are
      required to clarify the safety of heparin bridging therapy.

PMID- 27867825
TI  - Evolution, opportunity and challenges of transboundary water and energy problems
      in Central Asia.
AB  - Central Asia is one of the regions that suffer the most prominent transboundary
      water and energy problems in the world. Effective transboundary water-energy
      resource management and cooperation are closely related with socioeconomic
      development and stability in the entire Central Asia. Similar to Central Asia,
      Northwest China has an arid climate and is experiencing a water shortage. It is
      now facing imbalanced supply-demand relations of water and energy resources.
      These issues in Northwest China and Central Asia pose severe challenges in the
      implementation of the Silk Road Economic Belt strategy. Based on the analysis of
      water and energy distribution characteristics in Central Asia as well as demand
      characteristics of different countries, the complexity of local transboundary
      water problems was explored by reviewing corresponding historical problems of
      involved countries, correlated energy issues, and the evolution of inter-country
      water-energy cooperation. With references to experiences and lessons of five
      countries, contradictions, opportunities, challenges and strategies for
      transboundary water-energy cooperation between China and Central Asia were
      discussed under the promotion of the Silk Road Economic Belt construction based
      on current cooperation conditions.

PMID- 27867826
TI  - Development of intron polymorphism markers in major latex-like protein gene for
      locality-level and cultivar identification of Salvia miltiorrhiza.
AB  - BACKGROUND: Salvia miltiorrhiza (Danshen) is one of the most widely used
      medicinal herbs in traditional Chinese medicine. Locality-level and cultivar
      identification is of great importance not only for protecting highest therapeutic
      effectiveness of Daodi Danshen, but also for the genetic conservation and
      utilization of existing S. miltiorrhiza populations. RESULTS: Intron
      polymorphisms including SNPs (single nucleotide polymorphisms) and indels were
      exploited in major latex-like protein (MLP) gene. Based on these markers, genetic
      relationships among S. miltiorrhiza cultivar and populations in different
      locations were evaluated by constructing a dendrogram. Moreover, S. miltiorrhiza
      specimens from Laiwu region were geographically distinguishable by the developed
      SNP marker. A 204 bp-indel marker was exploited for the first space breeding
      cultivar Luyuan Danshen-1 (LD-1), and an effective real-time PCR assay was
      successfully developed for fast screening of LD-1 among local landraces.
      CONCLUSIONS: MLP intron is a valuable DNA barcode for intra-specific study of S.
      miltiorrhiza populations, and the developed markers can serve as a useful tool
      for molecular identification of LD-1 cultivar and geographically distinct
      populations of S. miltiorrhiza.

PMID- 27867827
TI  - An empirical evaluation of software quality assurance practices and challenges in
      a developing country: a comparison of Nigeria and Turkey.
AB  - BACKGROUND: The importance of quality assurance in the software development
      process cannot be overemphasized because its adoption results in high reliability
      and easy maintenance of the software system and other software products. Software
      quality assurance includes different activities such as quality control, quality
      management, quality standards, quality planning, process standardization and
      improvement amongst others. The aim of this work is to further investigate the
      software quality assurance practices of practitioners in Nigeria. While our
      previous work covered areas on quality planning, adherence to standardized
      processes and the inherent challenges, this work has been extended to include
      quality control, software process improvement and international quality standard
      organization membership. It also makes comparison based on a similar study
      carried out in Turkey. The goal is to generate more robust findings that can
      properly support decision making by the software community. The qualitative
      research approach, specifically, the use of questionnaire research instruments
      was applied to acquire data from software practitioners. RESULTS: In addition to
      the previous results, it was observed that quality assurance practices are quite
      neglected and this can be the cause of low patronage. Moreover, software
      practitioners are neither aware of international standards organizations or the
      required process improvement techniques; as such their claimed standards are not
      aligned to those of accredited bodies, and are only limited to their local
      experience and knowledge, which makes it questionable. The comparison with Turkey
      also yielded similar findings, making the results typical of developing
      countries. The research instrument used was tested for internal consistency using
      the Cronbach's alpha, and it was proved reliable. CONCLUSION: For the software
      industry in developing countries to grow strong and be a viable source of
      external revenue, software assurance practices have to be taken seriously because
      its effect is evident in the final product. Moreover, quality frameworks and
      tools which require minimum time and cost are highly needed in these countries.

PMID- 27867828
TI  - Evaluating the effectiveness of public hospital reform from the perspective of
      efficiency and quality in Guangxi, China.
AB  - The evaluation of hospital reform effectiveness in health care reform is very
      important and beneficial since it helps the government to understand the current
      situation of pilot county public hospitals and smoothly start the reform in all
      county hospitals. This study used sample hospitals data from 2010 to 2012 to
      evaluate the effectiveness of public hospital reform through comparisons between
      2010 and 2012 in hospital operating efficiency, clinical terminal quality, the
      average medical expense of patients, patient and medical staff overall
      satisfaction. The results highlight that there was no improvement in hospitals'
      operating efficiency, pilot hospitals' clinical terminal quality was lower than
      its counterpart, and the two objectives had been improved: medical expense
      control and inpatients' satisfaction, however, nearly 68.46% medical staffs were
      dissatisfied with the outcomes of the reform in pilot hospitals staff
      satisfaction. Nevertheless, the reform was helpful to improve the hospital
      current situation with some of the objectives having been achieved. It has not
      completely succeeded in Guangxi, China.

PMID- 27867829
TI  - Intrathecal/Intraventricular Linezolid in Multidrug-Resistant Enterococcus
      faecalis Ventriculitis.
AB  - Background The use of intrathecal antibiotic therapy for the treatment of
      ventriculitis and/or meningitis has demonstrated efficacy especially when
      sterilization of the cerebrospinal fluid is not possible with intravenous
      antibiotics alone. Case Description We describe the successful treatment of
      Enterococcus faecalis ventriculitis utilizing intrathecal linezolid in a 32-year
      old female patient with severe allergy to vancomycin, prohibitive bacterial
      susceptibilities, and failure of previous attempts to sterilize the cerebrospinal
      fluid despite multimodal treatment. Conclusion Intrathecal linezolid is a useful
      treatment in the setting of multidrug-resistant bacterial ventriculitis. We
      present a useful dosing regimen for the administration of intrathecal linezolid.

PMID- 27867830
TI  - Niche construction, social cognition, and language: hypothesizing the human as
      the production of place.
AB  - New data is emerging from evolutionary anthropology and the neuroscience of
      social cognition on our species-specific hyper-cooperation (HC). This paper
      attempts an integration of third-person archaeological and second-person,
      neuroscientific perspectives on the structure of HC, through a post-Ricoeurian
      development in hermeneutical phenomenology. We argue for the relatively late
      evolution of advanced linguistic consciousness (ALC) (Hiscock in Biological
      Theory 9:27-41, 2014), as a reflexive system based on the 'in-between' or
      'cognitive system' as reported by Vogeley et al. (in: Interdisziplinare
      anthropologie, Heidelberg, Springer, 2014) of face-to-face social cognition, as
      well as tool use. The possibility of a positive or negative tension between the
      more recent ALC and the more ancient, pre-thematic, self-organizing 'in-between'
      frames an 'internal' niche construction. This indexes the internal structure of
      HC as 'convergence', where complex, engaged, social reasoning in ALC mirrors the
      cognitive structure of the pre-thematic 'in-between', extending the bio-energy of
      our social cognition, through reflexive amplification, in the production of
      'social place' as 'humanized space'. If individual word/phrase acquisition, in
      contextual actuality, is the distinctive feature of human language (Hurford in
      European Reviews 12:551-565, 2004), then human language is a hyperbolic, species
      wide training in particularized co-location, developing consciousness of a shared
      world. The humanization of space and production of HC, through co-location,
      requires the 'disarming' of language as a medium of control, and a foregrounding
      of the materiality of the sign. The production of 'hyper-place' as solidarity
      beyond the face-to-face, typical of world religions, becomes possible where
      internal niche construction as convergence with the 'in-between' (world in us)
      combines with religious cosmologies reflecting an external 'cosmic' niche
      construction (world outside us).

PMID- 27867831
TI  - Examining ecological validity in social interaction: problems of visual fidelity,
      gaze, and social potential.
AB  - Social interaction is an essential part of the human experience, and much work
      has been done to study it. However, several common approaches to examining social
      interactions in psychological research may inadvertently either unnaturally
      constrain the observed behaviour by causing it to deviate from naturalistic
      performance, or introduce unwanted sources of variance. In particular, these
      sources are the differences between naturalistic and experimental behaviour that
      occur from changes in visual fidelity (quality of the observed stimuli), gaze
      (whether it is controlled for in the stimuli), and social potential (potential
      for the stimuli to provide actual interaction). We expand on these possible
      sources of extraneous variance and why they may be important. We review the ways
      in which experimenters have developed novel designs to remove these sources of
      extraneous variance. New experimental designs using a 'two-person' approach are
      argued to be one of the most effective ways to develop more ecologically valid
      measures of social interaction, and we suggest that future work on social
      interaction should use these designs wherever possible.

PMID- 27867832
TI  - A neuroimaging point of view on the diversity of social cognition: evidence for
      extended influence of experience- and emotion-related factors on face processing.
AB  - Faces are key social stimuli that convey a wealth of information essential for
      person perception and adaptive interpersonal behaviour. Studies in the domain of
      cognitive, affective, and social neuroscience have put in light that the
      processing of faces recruits specific visual regions and activates a distributed
      set of brain regions related to attentional, emotional, social, and memory
      processes associated with the perception of faces and the extraction of the
      numerous information attached to them. Studies using neuroimaging techniques such
      as functional magnetic resonance imaging (fMRI) have allowed localizing these
      brain regions and characterizing their functional properties.
      Magnetoencephalography (MEG) and electroencephalography (EEG) techniques are
      complementary to fMRI in that they offer a unique insight into the temporal
      dynamics of mental processes. In this article, I review the contribution of
      neuroimaging techniques to the knowledge on face processing and person perception
      with the aim of putting in light the extended influence of experience-related
      factors, particularly in relation with emotions, on the face processing system.
      Although the face processing network has evolved under evolutionary selection
      pressure related to sociality-related needs and is therefore highly conserved
      throughout the human species, neuroimaging studies put in light both the
      extension and the flexibility of the brain network involved in face processing.
      MEG and EEG allow in particular to reveal that the human brain integrates emotion
      and experience-related information from the earliest stage of face processing.
      Altogether, this emphasizes the diversity of social cognitive processes
      associated with face perception.

PMID- 27867833
TI  - Audience effects: what can they tell us about social neuroscience, theory of mind
      and autism?
AB  - An audience effect arises when a person's behaviour changes because they believe
      someone else is watching them. Though these effects have been known about for
      over 110 years, the cognitive mechanisms of the audience effect and how it might
      vary across different populations and cultures remains unclear. In this review,
      we examine the hypothesis that the audience effect draws on implicit mentalising
      abilities. Behavioural and neuroimaging data from a number of tasks are
      consistent with this hypothesis. We further review data suggest that how people
      respond to audiences may vary over development, personality factors, cultural
      background and clinical diagnosis including autism and anxiety disorder. Overall,
      understanding and exploring the audience effect may contribute to our models of
      social interaction, including reputation management and mentalising.

PMID- 27867835
TI  - Combined 13C-assisted metabolomics and metabolic flux analysis reveals the
      impacts of glutamate on the central metabolism of high beta-galactosidase
      producing Pichia pastoris.
AB  - BACKGROUND: Pichia pastoris is a popular recombinant protein expression system
      for its accessibility of efficient gene manipulation and high protein production.
      Sufficient supply of precursors, energy, and redox cofactors is crucial for high
      recombinant protein production. In our present work, we found that the addition
      of glutamate improved the recombinant beta-galactosidase (beta-gal) production by
      P. pastoris G1HL. METHODS: To elucidate the impacts of glutamate on the central
      metabolism in detail, a combined 13C-assisted metabolomics and 13C metabolic flux
      analysis was conducted based on LC-MS/MS and GC-MS data. RESULTS: The pool sizes
      of intracellular amino acids were obviously higher on glucose/glutamate
      (Glc/Glu). The fluxes in EMP entry reaction and in downstream TCA cycle were 50
      and 67% higher on Glc/Glu than on Glc, respectively. While the fluxes in upstream
      TCA cycle kept almost unaltered, the fluxes in PPP oxidative branch decreased.
      CONCLUSION: The addition of glutamate leads to a remarkable change on the central
      metabolism of high beta-galactosidase-producing P. pastoris G1HL. To meet the
      increased demands of redox cofactors and energy for higher beta-galactosidase
      production on Glc/Glu, P. pastoris G1HL redistributes the fluxes in central
      metabolism through the inhibitions and/or activation of the enzymes in key nodes
      together with the energy and redox status.

PMID- 27867834
TI  - Neurobiology of Risk for Bipolar Disorder.
AB  - Bipolar disorder (BD) is a chronic mental illness which follows a relapsing and
      remitting course and requires lifetime treatment. The lack of biological markers
      for BD is a major difficulty in clinical practice. Exploring multiple
      endophenotypes to fit in multivariate genetic models for BD is an important
      element in the process of finding tools to facilitate early diagnosis, early
      intervention, prevention of new episodes, and follow-up of treatment response in
      BD. Reviewing of studies on neuroimaging, neurocognition, and biochemical
      parameters in populations with high genetic risk for the illness can yield an
      integrative perspective on the neurobiology of risk for BD. The most up-to-date
      data reveals consistent deficits in executive function, response inhibition,
      verbal memory/learning, verbal fluency, and processing speed in risk groups for
      BD. Functional magnetic resonance imaging (fMRI) studies report alterations in
      the activity of the inferior frontal gyrus, medial prefrontal cortex, and limbic
      areas, particularly in the amygdala in unaffected first-degree relatives (FDR) of
      BD compared to healthy controls. Risk groups for BD also present altered immune
      and neurochemical modulation. Despite inconsistencies, accumulating data reveals
      cognitive and imaging markers for risk and to a less extent resilience of BD.
      Findings on neural modulation markers are preliminary and require further
      studies. Although the knowledge on the neurobiology of risk for BD has been
      inadequate to provide benefits for clinical practice, further studies on
      structural and functional changes in the brain, neurocognitive functioning, and
      neurochemical modulation have a potential to reveal biomarkers for risk and
      resilience for BD. Multimodal, multicenter, population-based studies with large
      sample size allowing for homogeneous subgroup analyses will immensely contribute
      to the elucidation of biological markers for risk for BD in an integrative model.

PMID- 27867836
TI  - Detecting structural variances of Co3O4 catalysts by controlling beam-induced
      sample alterations in the vacuum of a transmission electron microscope.
AB  - This article summarizes core aspects of beam-sample interactions in research that
      aims at exploiting the ability to detect single atoms at atomic resolution by mid
      voltage transmission electron microscopy. Investigating the atomic structure of
      catalytic Co3O4 nanocrystals underscores how indispensable it is to rigorously
      control electron dose rates and total doses to understand native material
      properties on this scale. We apply in-line holography with variable dose rates to
      achieve this goal. Genuine object structures can be maintained if dose rates
      below ~100 e/A2s are used and the contrast required for detection of single atoms
      is generated by capturing large image series. Threshold doses for the detection
      of single atoms are estimated. An increase of electron dose rates and total doses
      to common values for high resolution imaging of solids stimulates object
      excitations that restructure surfaces, interfaces, and defects and cause grain
      reorientation or growth. We observe a variety of previously unknown atom
      configurations in surface proximity of the Co3O4 spinel structure. These are
      hidden behind broadened diffraction patterns in reciprocal space but become
      visible in real space by solving the phase problem. An exposure of the Co3O4
      spinel structure to water vapor or other gases induces drastic structure
      alterations that can be captured in this manner.

PMID- 27867837
TI  - Identifying local structural states in atomic imaging by computer vision.
AB  - The availability of atomically resolved imaging modalities enables an
      unprecedented view into the local structural states of materials, which manifest
      themselves by deviations from the fundamental assumptions of periodicity and
      symmetry. Consequently, approaches that aim to extract these local structural
      states from atomic imaging data with minimal assumptions regarding the average
      crystallographic configuration of a material are indispensable to advances in
      structural and chemical investigations of materials. Here, we present an approach
      to identify and classify local structural states that is rooted in computer
      vision. This approach introduces a definition of a structural state that is
      composed of both local and nonlocal information extracted from atomically
      resolved images, and is wholly untethered from the familiar concepts of symmetry
      and periodicity. Instead, this approach relies on computer vision techniques such
      as feature detection, and concepts such as scale invariance. We present the
      fundamental aspects of local structural state extraction and classification by
      application to simulated scanning transmission electron microscopy images, and
      analyze the robustness of this approach in the presence of common instrumental
      factors such as noise, limited spatial resolution, and weak contrast. Finally, we
      apply this computer vision-based approach for the unsupervised detection and
      classification of local structural states in an experimental electron micrograph
      of a complex oxides interface, and a scanning tunneling micrograph of a defect
      engineered multilayer graphene surface.

PMID- 27867839
TI  - Reward Contrast Effects on Impulsive Choice and Timing in Rats.
AB  - Despite considerable interest in impulsive choice as a predictor of a variety of
      maladaptive behaviors, the mechanisms that drive choice behavior are still poorly
      understood. The present study sought to examine the influence of one understudied
      variable, reward magnitude contrast, on choice and timing behavior as changes in
      magnitude commonly occur within choice procedures. In addition, assessments of
      indirect effects on choice behavior through magnitude-timing interactions were
      assessed by measuring timing within the choice task. Rats were exposed to choice
      procedures composed of different pairs of magnitudes of rewards for either the
      smaller-sooner (SS) or larger-later (LL) option. In Phase 2, the magnitude of
      reward either increased or decreased by 1 pellet in different groups (LL increase
      = 1v1->1v2; SS decrease = 2v2 -> 1v2; SS increase = 1v2 -> 2v2), followed by a
      return to baseline in Phase 3. Choice behavior was affected by the initial
      magnitudes experienced in the task, demonstrating a strong anchor effect. The
      nature of the change in magnitude affected choice behavior as well. Timing
      behavior was also affected by the reward contrast manipulation albeit to a lesser
      degree and the timing and choice effects were correlated. The results suggest
      that models of choice behavior should incorporate reinforcement history, reward
      contrast elements, and magnitude-timing interactions, but that direct effects of
      reward contrast on choice should be given more weight than the indirect reward
      timing interactions. A better understanding of the factors that contribute to
      choice behavior could supply key insights into this important individual
      differences variable.

PMID- 27867840
TI  - Instrumentation for minimally invasive surgery in pediatric urology.
AB  - The success of modern surgery is dependent on the availability of good equipment
      and instruments. This dependence increases along with the degree of
      sophistication of the surgery performed. Paediatric minimally invasive and
      endoscopic surgery are sophisticated techniques where imaging is obtained through
      a video-circuit. Endoscopic surgery has opened the field of virtual reality in
      surgery, and in minimally invasive surgery the actual operation is done through a
      limited number of small holes. Robot-assisted urologic surgery is an emerging and
      safe technology for many urologic paediatric operations, although further
      documentation, including long-term functional outcome, is deemed necessary before
      definite conclusions can be drawn regarding the superiority or not of robotic
      assistance compared to conventional laparoscopic approaches.

PMID- 27867838
TI  - Advances in miRNA-Mediated Mucin Regulation.
AB  - MicroRNAs (miRNAs) are an important class of small non-coding RNAs that direct
      post-transcriptional gene regulation by different mechanisms. Mounting evidences
      from numerous studies in the last decade have unraveled that deregulated miRNAs,
      and their cognate target expressions are strongly implicated in the
      carcinogenesis. Recent advances have highlighted miRNA-mediated regulation of
      mucins that have critical role in inflammation and cancer biology. The aberrant
      expression and differential glycosylation of mucins cause tumorigenesis,
      metastasis, chemoresistance and poor outcome of cancer patients, thus recognizing
      them as attractive therapeutic targets. Though current mucin-based therapies
      (antibodies, vaccines, immunotherapy, peptide inhibitors) have shown preclinical
      utility but only a handful promise for clinical transferability. In this context,
      understanding miRNA-mediated modulation of multiple mucin(s) expression and
      function gives a new hope for future anti-tumor therapeutics. Herein, we reviewed
      miRNA biogenesis, mechanism of action, and their role in tumor development.
      Further, we provide an overview of miRNA-mediated mucin regulation and their
      application as anticancer therapeutics.

PMID- 27867843
TI  - The laparoscopic approach for repair of indirect inguinal hernias in infants and
      children.
AB  - Repair of an indirect inguinal hernia is one of the most common operations
      performed around the world by pediatric surgeons. Until the last 15 years, most
      inguinal hernia repairs were performed using an inguinal crease incision and
      extraperitoneal ligation of the patent processes vaginalis. However, since 2000,
      the laparoscopic approach has gained popularity and there have been increasing
      descriptions about various techniques for laparoscopic hernia (LH) repair. At our
      institution, we have transitioned the majority of inguinal hernia repairs to the
      laparoscopic approach. In this article, we will describe the technique that is
      utilized at Children's Mercy Hospital in Kansas City, Missouri (USA) and express
      our thoughts on the current debate regarding laparoscopic versus open inguinal
      hernia repair in infants and children.

PMID- 27867841
TI  - Laparoscopy or retroperitoneoscopy: which is the best approach in pediatric
      urology?
AB  - The emergence of minimally invasive surgery about 20 years ago revolutionized
      pediatric urology. Advances in pediatric devices allowed the widespread use of
      minimally invasive techniques in almost the entire range of pediatric urology. In
      this context, laparoscopy and later retroperitoneoscopy were developed and
      applied in a wide spectrum of urological diseases. Both approaches have since
      presented benefits and disadvantages that have been documented in various series.
      However, few comparative studies have been conducted. The aim of this review is
      to compare the two approaches and establish which is preferable in each field of
      pediatric urology.

PMID- 27867842
TI  - Pediatric anesthesia for minimally invasive surgery in pediatric urology.
AB  - Laparoscopic or robotic minimally invasive approaches have become the standard of
      care for many urological pediatric surgical procedures. Anesthetic concerns for
      conventional and robotic laparoscopy are similar since they both require
      insufflations of CO2 to allow visualization of surgical field and perform
      surgery. Even if required insufflation pressures and volumes are lower in
      pediatric patients (given the small size of the abdomen and laxity of the
      abdominal walls), the associated increase of intra-abdominal pressure, along with
      absorption of CO2 and surgical positioning requirement, may result in
      neurendocrine and mechanical impact capable to mine cardiopulmonary function.
      Moreover, laparoscopic approach may require specific positioning. A correct
      positioning is essential to allow the surgical team to optimally and safely
      access to the patient. The knowledge of patient's health status, along with the
      multiple physiologic changes that can occur and specific potential complications,
      allow the anesthesiologist to provide a safer an aesthesia.

PMID- 27867844
TI  - Surgical approaches for varicocele in pediatric patient.
AB  - BACKGROUND: Varicocele represents one of the most common surgically correctible
      urologic anomalies in adolescent males. The best procedure for the treatment of
      adolescent varicocele has not been established, but with recent advances in
      minimal access surgery, there have been many reports praising the safety and
      efficacy of laparoscopy and retroperitoneoscopy for the surgical correction of
      varicocele in adolescent. The aim of this review is to compare the results of
      Palomo's technique, with retroperitoneoscopic and transperitoneoscopic approaches
      in adolescent, analyzing recurrence, testicular growth and complications.
      METHODS: A literature search on PubMed and Cochrane Database was conducted with
      regard to management of varicocele in adolescent population. Twenty two English
      language studies that compared outcome of different minimally invasive treatments
      or outcome of minimally invasive and traditional surgical treatments for
      adolescent diagnosed with varicocele were included. RESULTS: Intraoperative
      complications of minimally invasive approaches occur in early cases, but in
      pediatric urology these procedures would become more efficient with experience
      and these approaches continue to increase in number. Postoperative hydrocele is
      the most postoperative compliance of Palom technique, and reports have shown a
      wide range of variability for his incidence, depending on the technique used for
      surgical treatment. Literature showed an increase of testicular volume for real
      growth of testis after surgery, and an intratesticular improvement in sperm
      quality after minimally invasive approach. In laparoscopic approach reports have
      showed very low recurrence because allows better vision of collateral veins, and
      a lymphatic sparing technique permit to identify lymphatic vessels in 100% of
      cases. CONCLUSIONS: The literature has shown that laparoscopic varicocelectomy is
      the surgical approach most commonly reported in adolescent patients, and that its
      use is increasing for better training for surgeons and the ability to avoid
      operational hydrocele that is a main complication after technical Palomo's
      technique.

PMID- 27867845
TI  - Current management of non-palpable testes: a literature review and clinical
      results.
AB  - Cryptorchidism is a common pathology that occurs in 3% in full term newborns, and
      it decreases to 0.8-1.2% at 1 year of age. Nearly a 20% of undescended testes are
      non-palpable. Various surgical treatments have been described, but its management
      is still controversial. A literature review was made of non-palpable testes,
      analysing diagnostic tools, treatment and its results. Additionally we reviewed
      non-palpable testes cases treated in our centre in the last 20 years. Different
      techniques are described for the management of non-palpable testes; with or
      without section of the spermatic vessels and/or in 1 or 2 stages. Nowadays,
      literature supports the laparoscopic management in two stages. In our experience,
      we have better results in two-stage Fowler-Stephens than one-stage, with lower
      rates of testicular atrophy. Non-palpable testes are a common pathology in
      paediatric urology. Analysing the literature and our experience we recommend a
      two-stage surgery for intra-abdominal testes, which has demonstrated good results
      and lower percentage of atrophic testis.

PMID- 27867846
TI  - What's the best minimal invasive approach to pediatric nephrectomy and
      heminephrectomy: conventional laparoscopy (CL), single-site (LESS) or robotics
      (RAS)?
AB  - BACKGROUND: Conventional laparoscopy (CL) using 3-5 mm ports has become the
      goldstandard for pediatric nephrectomy (N), heminephrectomy (HN) and
      heminephrecto-ureterectomy (HNU) for many years now. Recently the spectrum of
      minimal invasive surgery (MIS) has been extended by variants like
      laparoendoscopic single-site surgery (LESS) or robot-assisted surgery (RAS).
      However such technical developments tend to drive surgical euphoria and
      feasibility studies, but may miss adequate academic research about function and
      proven patients' benefits. This article delivers a comprehensive analysis of
      present pediatric studies comparing at least two MIS approaches to N, HN and HNU.
      METHODS: A systematic literature-based search for studies published between 2011
      2016 about CL versus LESS or RAS for pediatric N, HN, and HNU was performed using
      multiple electronic databases and sources. The level of evidence was determined
      using the Oxford Centre for Evidence-based Medicine (OCEBM) criteria. Single arm
      observational studies about N, HN or HNU using CL, LESS or RAS as well as
      publications including adult patients were excluded. RESULTS: A total of 11
      studies met defined inclusion criteria, reporting on CL versus LESS or RAS. No
      studies of OCEBM Level 1 or 2 were identified. Performing CL for N and HN limited
      evidence indicated reduced analgesic requirements and shorter hospital stay over
      open surgery, but longer operating time. Preservation of renal function of the
      remaining moiety after CL-HN was 95%. Importantly, of patients losing their
      remaining moiety, median age at surgery was 9 months (range, 4-42 months), and
      all except 1 (6/7) had an upper pole HN. Several authors compared TNP versus RPN
      access for CL and confirmed a longer operating time for RPN versus TPN-NU.
      Moreover one study reported a longer ureteric stump in RPN versus TPN-HNU (range,
      2-5 cm vs. 3-7 mm). Disadvantages of LESS or RAS over CL were longer operative
      time and higher total costs (RAS). There were no differences regarding
      complications, success rates, or short-term outcomes between pediatric RAS versus
      CL. No long-term studies about preservation of renal function or length of
      ureteric stump using LESS or RAS could be retrieved. CONCLUSIONS: Several
      approaches to MIS-NU and HNU are available today. CL represents the method of
      choice for any age group. TPN or RPN can be chosen according to age of the
      patient. LESS and RAS offer distinct advantages, but also lack evident patients'
      benefits over CL at present. Hopefully, as pediatric MIS advances over the next
      decade, larger studies comparing CL, LESS or RAS directly for pediatric NU and
      HNU will be published to gain a higher level of evidence what's really best for
      the child.

PMID- 27867847
TI  - Retroperitoneal and laparoscopic heminephrectomy in duplex kidney in infants and
      children.
AB  - BACKGROUND: Two main techniques are adopted to perform partial nephrectomy in
      children: laparoscopy and retroperitoneoscopy. The aim of this paper is to review
      the larger multicentric experience recently published by our group to review
      indications, techniques and results of both approaches. METHODS: Data of 102
      patients underwent partial nephrectomy in a 5-year period using minimally
      invasive surgery (MIS) procedures were analyzed. Fifty-two children underwent
      laparoscopic partial nephrectomy (LPN), and 50 children underwent
      retroperitoneoscopic partial nephrectomy (RPN). Median age at surgery was 4.2
      years. Statistical analysis was performed using chi2 test and Student's t-test.
      RESULTS: The overall complications rate was significantly higher after RPN
      (15/50, 30%) than after LPN (10/52, 19%) (chi2 =0.05). In LPN group,
      complications [4 urinomas, 2 symptomatic refluxing distal ureteral stump (RDUS)
      and 4 urinary leakages] were conservatively managed. In RPN group, complications
      (6 urinomas, 8 RDUS, 1 opening of remaining calyxes) required a re-operation in 2
      patients. In both groups no conversion to open surgery was reported. Operative
      time (LPN: 166.2 min vs. RPN: 255 min; P<0.001) and hospitalization (LPN: 3.5
      days vs. RPN: 4.1 days; P<0.001) were significantly shorter in LPN group. No
      postoperative loss of renal function was reported in both groups. CONCLUSIONS:
      MIS now represents the gold standard technique to perform partial nephrectomy in
      children with duplex kidney. Our results demonstrate that RPN remains a
      technically demanding procedure with a significantly higher complications and re
      operation rate compared to LPN. In addition, length of surgery and
      hospitalization were significantly shorter after LPN compared to RPN. LPN seems
      to be a faster, safer and technically easier procedure to perform in children
      compared to RPN due to a larger operative space and the possibility to perform a
      complete ureterectomy in refluxing systems.

PMID- 27867850
TI  - Minimal access surgery in the management of pediatric urolithiasis.
AB  - BACKGROUND: In contrast to adult patients, a relatively large number of open
      surgical procedures are still needed in the treatment of urolithiasis in
      children. Since almost all open surgical techniques may be reproduced by minimal
      access surgery (MAS), there is a rationale to apply the latter in the management
      of pediatric urolithiasis. Our study aimed to assess the feasibility and outcome
      of MAS in the treatment of pediatric urinary calculi. METHODS: The charts of
      patients with urolithiasis submitted to MAS between 1994 and 2007 were
      retrospectively reviewed. The inclusion criteria were contraindication for and
      failure of lithotripsy or endourology techniques. Demographic data, lithiasis
      characterization (location, dimension, composition), predisposing factors
      (anatomic or metabolic) and surgical approach (technique and outcome) were
      evaluated. RESULTS: Fifteen consecutive patients (eight girls, seven boys) with a
      median age of 108 months (range: 10-297 months) were elected for MAS. Eleven
      (73%) children had associated urogenital malformations and three (20%) presented
      metabolic abnormalities. A total of 17 procedures were performed
      laparoscopically: three nephrolithotomy (one transperitoneal, two by
      retroperitoneoscopy), four pyelolithotomies (retro), three ureterolithotomy
      (trans) and seven cystolithotomies (suprapubic approach). Five patients underwent
      concomitant correction of urological anomalies (three calyceal diverticula, one
      obstructive megaureter, one ureteropelvic junction obstruction). Complete removal
      of calculi was accomplished in 14 (82%) procedures. There were two perioperative
      complications (one intraperitoneal vesical perforation and one perivesical
      urinoma). At a median follow up of 4 years (range, 1 month to 11 years), four
      patients have developed recurrence. CONCLUSIONS: MAS is an effective and safe
      approach for urolithiasis in children who are not candidates for minimally
      invasive modalities.

PMID- 27867848
TI  - Pyeloplasty techniques using minimally invasive surgery (MIS) in pediatric
      patients.
AB  - Hydronephrosis is the most common presentation of ureteropelvic junction (UPJ)
      obstruction. We reviewed literature, collecting data from Medline, to evaluate
      the current status of minimally invasive surgery (MIS) approach to pyeloplasty.
      Since the first pyeloplasty was described in 1939, several techniques has been
      applied to correct UPJ obstruction, but Anderson-Hynes dismembered pyeloplasty is
      established as the gold standard, to date also in MIS technique. According to
      literature several studies underline the safety and effectiveness of this
      approach for both trans- and retro-peritoneal routes, with a success rate between
      81-100% and an operative time between 90-228 min. These studies have demonstrated
      the safety and efficacy of this procedure in the management of UPJ obstruction in
      children. Whether better the transperitoneal, than the retroperitoneal approach
      is still debated. A long learning curve is needed especially in suturing and
      knotting.

PMID- 27867849
TI  - Laparoscopic transposition of lower pole crossing vessels (vascular hitch) in
      children with pelviureteric junction obstruction.
AB  - BACKGROUND: Congenital hydronephrosis due to intrinsic or extrinsic uretero
      pelvic-junction (UPJ) obstruction (UPJO) is a common problem in childhood UPJO
      may be caused by intrinsic disorganization or by extrinsic compression from
      crossing vessels (CV); extrinsic causes usually present symptomatically in older
      children. This report the large Italian experience in the treatment of children
      with extrinsic-UPJO by CV. METHODS: We analyzed the data of 51 children (17 girls
      and 34 boys, median age 10, 7 years) affected by extrinsic-UPJO were treated in
      three Italian institutions with laparoscopic transposition of CV (Hellstrom
      Vascular Hitch modified by Chapman).The intraoperative diuretic-test was
      performed in all patients before and after the vessels transpositions confirming
      the extrinsic-UPJO. We included in the study only patients with suspicion of
      vascular extrinsic obstruction of the UPJ. Symptoms at presentation were
      recurrent abdominal/flank pain and haematuria. All patients presented
      intermittent ultrasound (US) detection of hydronephrosis (range, 18-100 mm).
      Preoperative diagnostic studies included: US/doppler scan, MAG3-renogram,
      functional-magnetic-resonance-urography (fMRU). RESULTS: Median operative time
      was 108 minutes; median hospital stay: 3, 4 days. Unique complications: a small
      abdominal wall hematoma and higher junction-translocation without obstruction.
      During follow-up (range, 12-96 months) all patients reported resolution of their
      symptoms, a decrease in the hydronephrosis grade and improved drainage on
      diuretic renogram. CONCLUSIONS: We believe that Vascular Hitch is less
      technically demanding than laparoscopic pyeloplasty, resulting in a lower
      complication rate and a significantly reduced hospitalization. The results of our
      study allow us to conclude that laparoscopic VH may be a safe, feasible, and
      attractive alternative to treat obstructed hydronephrosis due to CV presenting a
      useful alternative to AHDP in the management of symptomatic children where CV are
      deemed the sole aetiology. We recommend careful patient selection based on
      preoperative clinical and radiologic findings that are diagnostic of extrinsic
      UPJO, combined with intraoperative-DT to confirm the appropriate selection of
      corrective procedure.

PMID- 27867851
TI  - Percutaneous endoscopic treatment for urinary stones in pediatric patients: where
      we are now.
AB  - BACKGROUND: Percutaneous nephrolithotomy (PCNL) has been adopted for pyelo
      calyceal stones treatment in pediatric patients, starting from the 90's. Very
      recently, miniaturization of endoscopic instruments allowed less invasive
      procedures with low complication rate. We reviewed our experience on upper tract
      stone treatment utilizing two different percutaneous accesses, focusing on the
      recent new miniaturized devices offered for pediatric renal stones. METHODS:
      Patients presenting upper tract urinary stones observed from January 2011 to
      December 2015 and treated by percutaneous renal access were prospectively
      evaluated: age, sex, metabolic issues, associated abnormalities, treatment
      modalities, hospital stay and complication rate were recorded in a specific
      database. Two different endourological percutaneous modalities were adopted,
      depending to the stone size and position. PCNL was performed through a direct
      calyceal puncture under ultrasonographic and fluoroscopic guidance and Amplatz
      access dilatation till 24 Fr. Ballistic energy was used for fragmentation.
      Micropercutaneous (Microperc) procedure was recently offered utilizing a 4.85 Fr
      metallic needle and Holmium:YAG laser lithotripsy under direct vision through a
      0.9 mm high resolution optic flexible wire connected with a telescope. RESULTS:
      Thirty-eight percutaneous access to pyelo-calyceal renal stones were performed on
      a total of 108 children treated for upper tract stones, aged 4 to 18 years (mean
      age 7.5 years). The overall number of procedures was 144 (36 repeated
      procedures). Cystinuria was diagnosed in 5 patients. PCNL was adopted in 28
      patients, Microperc was utilized in 8 patients. Hemoglobin dropdown was limited
      to 1.20+/-0.80 mg% in PCNL and was not significant in Microperc. No blood
      transfusion was needed. No significant complications were observed. Stone free
      rate or minimal not significant residuals were achieved in 82% of PCNL and in
      87.5% of Microperc, after a single procedure. CONCLUSIONS: Percutaneous
      endoscopic treatment of renal calculi is feasible in pediatric age, with high
      success rate in a single step. Advanced miniaturized endoscopic devices as
      Microperc guarantee high efficacy and reduced complication rate, but endo
      urological experience and adequate learning curve are required, especially in
      small body weight children. Centralization of these patients in Pediatric Stone
      Centers is welcomed to optimize results and reduce risks.

PMID- 27867852
TI  - Laparoscopic management of urachal cysts.
AB  - BACKGROUND: The urachus and the urachal remnants represent a failure in the
      obliteration of the allantois at birth that connects the bladder to the
      umbilicus. After birth it obliterates and presents as the midline umbilical
      ligament. Urachal cyst are the most common urachal anomaly in the pediatric
      population. The traditional surgical approach is a semicircular infraumbilical
      incision or a lower midline laparotomy. METHODS: In a 10 years period at
      Pediatric Surgery Department of Vicenza 16 children were diagnosed with urachal
      anomalies presenting as abdominal or urinary symptoms. Eight underwent open
      excision; eight were treated by laparoscopic surgery. The average age was 5.5
      years (range, 4 months-13 years) in open group and 10 years (range, 1 month-18
      years) in laparoscopic group. RESULTS: Mean operative time was 63 minutes (range,
      35-105 minutes) in open group, 50 minutes (range, 35-90 minutes) in laparoscopic
      group. There were no postoperative complications. The patients of laparoscopic
      group were all discharged after few days (range, 2-4 days). Pathological
      examination confirmed a benign urachal remnant in all cases. Reporting our
      experience since comparing the two surgical approaches we want to describe the
      technique step by step of laparoscopic urachal cyst excision as minimally
      invasive diagnostic and surgical techniques. CONCLUSIONS: Laparoscopy represents
      a useful alternative for the management of persistent or infected urachus, in
      particular when there's the suspect despite the lack of radiological evidence.
      The morbidity associated with this approach is very low as the risk or
      recurrence. Laparoscopy in the management of urachal cyst is safe effective and
      ensures good cosmesis with all the advantages of minimally invasive approach.

PMID- 27867854
TI  - Laparoscopic extravesical ureteral reimplantation (LEVUR): a systematic review.
AB  - BACKGROUND: Laparoscopic ureteral reimplantation is a feasible method for
      treating ureteral pathology with good preliminary results in the literature. In
      this study, we review medium term results for laparoscopic ureteral
      reimplantation and discuss current developments of this procedure. METHODS:
      Medline and Embase databases were searched using relevant key terms to identify
      reports of paediatric laparoscopic extravesical ureteral reimplantation (LEVUR).
      Literature reviews, case reports, series of <3 children and adult studies (age
      >20 years) were excluded. RESULTS: Five studies were assessed, overall, 69 LEVUR
      were performed in children. Despite different surgical technique, in all case the
      technique was respected. Patient demographics, preoperative symptoms,
      radiological imaging, complications, and postoperative outcomes were analyzed.
      Median success rate was 96%. Complications were reported in five cases.
      CONCLUSIONS: This study is limited by the data given in the individual series:
      varied criteria used for patient selection and outcome as well as inconsistent
      pre- and post-operative imaging data precluded a meta-analysis. But it
      demonstrates that the laparoscopic ureteral reimplantation is an effective
      procedure with good medium-term results. We believe that in well selected
      patients this procedure will become an established treatment option.

PMID- 27867853
TI  - Treatment of vesico-ureteral reflux in infants and children using endoscopic
      approaches.
AB  - Vesicoureteral reflux (VUR) represents one of the most significant risk factors
      for acute pyelonephritis in children. Endoscopic treatment of VUR dates back to
      1981 when Matouschek first described injection of the ureteral orifice in an
      attempt to correct VUR. In addition, also Politano and colleagues and McDonald
      described successful correction of reflux using endoscopic techniques. After
      these reports subureteral Teflon injection (STING) came to be appreciated as a
      viable new way to less invasively correct one of the most common pediatric
      urologic problems. The technique is technically easy to perform and is usually
      performed as an outpatient procedure. It is performed in general anesthesia in
      children and may require repeat injections, particularly in patients with high
      grade reflux. As for endoscopic technique, a main problem existed. The success in
      children with high grade reflux was less than reported for open or laparoscopic
      reimplant techniques. However, in the past 10 years, newer products have become
      available that are changing the indications for endoscopic correction. In these
      review, we analyzed the papers published in the literature on this topic to give
      to the readers an updated overview about the results of endoscopic treatment of
      VUR after 30-years of his first description.

PMID- 27867855
TI  - Laparoscopic approach for gonadectomy in pediatric patients with intersex
      disorders.
AB  - The birth of a child with a disorder of sex development (DSD) prompts a long-term
      management strategy that involves a myriad of professionals working with the
      family. There has been progress in diagnosis, surgical techniques and in
      understanding psychosocial issues related to this condition. However, since these
      kinds of disorders are rare and have many anatomical variations, individual care
      is necessary, especially regarding surgical management. Gonadectomy is indicated
      in a number of intersex disorders with a Y chromosome to reduce the associated
      risk of cancer. Recently, laparoscopy has gained wide acceptance in pediatric
      urology. Laparoscopy is also reported to be a useful tool for diagnosing and
      treating DSD because of its minimal invasiveness and favorable cosmetic outcome.
      However, reports of evaluation and management using laparoscopy for large numbers
      of DSD patients are limited and debate is still open about indications and timing
      of gonadectomy. In this study, we reviewed the literature of the last 10 years
      about the role of laparoscopic gonadectomy in patients with DSD. In the analyzed
      papers, all the procedures were accomplished successfully using laparoscopy. No
      conversions to open surgery neither intra-operative complications were reported
      in all series. Post-operative complications were reported only in one series and
      included 1 umbilical port infection [2% (1/50)] and 1 pelvic abscess [2% (1/50)],
      both treated with antibiotic therapy (grade I Clavien-Dindo). Of the analyzed
      series, 7/10 reported postoperative diagnosis of gonadal tumors. The
      histopathologic examinations revealed 15 cases of gonadoblastoma, 7 cases of
      dysgerminoma and 2 cases of seminoma. Analyzing the single series, the incidence
      of these tumors varied between 10% and 33%. The results of our review confirmed
      the safety and efficacy of laparoscopic gonadectomy in DSD patients. In our mind,
      laparoscopic gonadectomy should be accepted as the treatment of choice in
      children and adolescents with these rare conditions. It thereby eliminates the
      risk of malignancies of gonadal origin with the advantages of a minimally
      invasive procedure, with lower morbidity, quicker postoperative recovery and
      excellent cosmetic results.

PMID- 27867856
TI  - Minimally invasive surgery in management of renal tumours in children.
AB  - Minimally invasive surgery (MIS) in the management of malignant and benign renal
      tumours in children is gradually becoming more common. Experience is limited and
      restricted to case reports, retrospective chart reviews and a few cohort studies.
      There are currently no randomized controlled trials or controlled clinical trials
      comparing the laparoscopic and open surgical approach for the management of renal
      tumours in children. MIS may offer the same oncologic outcome in malignant renal
      tumours whilst providing the advantages associated with MIS in correctly selected
      cases. The technique for tumour resection has been shown to be feasible in
      regards to the recommended oncologic principles, although lymph node sampling can
      be inadequate in some cases. Preliminary reports do not show an increased risk of
      tumour rupture or inferior oncologic outcomes after MIS. However, the sample size
      remains small and duration of follow-up inadequate to draw any firm conclusions.
      Implementation of MIS is lacking in the protocols of the major study groups, and
      standardized recommendations for the indications and contra-indications remain
      undefined. The objective of this article is to present a review of the literature
      on the role of MIS in the management of renal tumours in children, with the main
      focus on Wilms' tumour (WT). Further studies on MIS in renal tumours are required
      to evaluate the incidence of oncological complications such as complete tumour
      resection and intra-operative tumour spillage. A long-term follow-up of patients
      managed by MIS is essential to compare recurrence rates and overall survival
      rates.

PMID- 27867857
TI  - Training for MIS in pediatric urology: proposition of a structured training
      curriculum.
AB  - In Europe there are a lot of training centers for minimally invasive surgery
      (MIS) but a standardized MIS training program in pediatric urology doesn't exist
      at the moment. We performed a literature review with the last goals to propose a
      structured training curriculum in MIS urology for pediatric surgeons. Pediatric
      urologists have to obtain a valid MIS training curriculum completing the
      following 4 steps: (I) Theoretical part (theoretical courses, masterclass) to
      acquire theoretical knowledge; (II) experimental training (simulation on pelvic
      trainer, virtual reality simulators, animal models, 3-D ex-vivo models) to
      acquire basic laparoscopic skills; (III) stages in European centers of reference
      for pediatric MIS urology to learn all surgery aspects; (IV) personal operative
      experience. At the end of the training period, the trainee would be expected to
      perform several MIS urological procedures independently, under supervision of an
      expert tutor. At the end of the training program, each center will analyze the
      candidate training booklet and release for each applicant a certification after
      an exam. We think that this MIS training program in pediatric urology may assure
      an integrated acquisition of basic and advanced laparoscopic skills during
      residency training in pediatric urology. Each European country should adopt this
      program so as to secure a standardized technical qualification in MIS urology for
      all future pediatric urologists.

PMID- 27867858
TI  - New techniques and technologies for the treatment of surgical endocrine diseases.

PMID- 27867859
TI  - New endoscopic procedures for diabetes mellitus type 2 and obesity treatment.
AB  - BACKGROUND: Obesity continues to be a growing epidemic worldwide. Obese patients
      have severe comorbidities that make risky and technically demanding the execution
      of bariatric surgery from both surgical and anesthetic point of view; therefore,
      the focus of bariatric surgeons is increasingly moving towards minimally
      invasive, endoscopic techniques. METHODS: The present review presents and
      discusses recent endoscopic techniques employed in obesity treatment, their
      features and results. RESULTS: Endoscopic treatment can be primary or revisional;
      we can mainly divide the endoscopic devices into five categories: space-occupying
      devices, restrictive procedures, bypass liner, aspiration therapy and endoscopic
      revision of gastric bypass for dilated gastric pouch. CONCLUSIONS: Endoscopic
      treatments for obesity are promising techniques for selected patients but each
      procedure should be tailored on the patient in a multimodal approach.

PMID- 27867860
TI  - Laparoscopic sleeve gastrectomy for the treatment of diabetes mellitus type 2
      patients-single center early experience.
AB  - BACKGROUND: In recent years, laparoscopic sleeve gastrectomy (LSG) has become one
      of the most commonly used primary bariatric procedures for morbid obesity. While
      laparoscopic Roux-en-Y gastric bypass (LRYGB) has well documented positive
      clinical influence on type 2 diabetes, the role of LSG in diabetes treatment is
      debatable. The main aim of this study is to present our early experience in LSG
      as a method of bariatric treatment in patients with type 2 diabetes or
      abnormalities in glucose homeostasis. METHODS: Prospectively collected data of
      patients operated for morbid obesity at the 2nd Department of Surgery. The study
      was designed to assess the influence of LSG on type 2 diabetes and glucose
      homeostasis. The primary endpoint was the diabetes type 2 remission. Secondary
      endpoint was the change of glucose metabolism parameters after LSG. Patients were
      assessed preoperatively and allocated to two groups: group 1-with any
      preoperative abnormalities in glucose homeostasis (prediabetes, diabetes) and
      group 2-with non-elevated fasting glucose level. During follow-up (6 months after
      surgery) all glucose homeostasis parameters were analyzed again. One hundred and
      thirty-six patients after LSG were enrolled in the study (90 females, 46 males;
      mean age 40.5+/-9.9 years). Preoperative abnormalities in glucose homeostasis
      were confirmed in 64 (47%) patients. Twenty (15%) patients in this group had
      diabetes. RESULTS: We observed significant reduction of body mass index (BMI)
      after surgery. Mean percent of EBMIL for all groups after 6 months from surgery
      was 59.90% (46.75-69.28%). There were no full remissions after surgery in
      patients with preoperative diabetes. We found significant improvement in
      biochemical markers of glucose homeostasis. We observed significant reduction of
      HbA1c% after surgery in both groups. The level of postoperative HbA1c% was
      related to BMI loss after surgery. CONCLUSIONS: LSG leads to significant
      improvement in biochemical glucose homeostasis and can be considered as a method
      of treatment in morbidly obese patients with glucose metabolism abnormalities.
      LSG as a method of treatment for patients with clinical type 2 diabetes still
      needs some further observation.

PMID- 27867861
TI  - Intraoperative neural monitoring in thyroid surgery: lessons learned from animal
      studies.
AB  - Recurrent laryngeal nerve (RLN) injury remains a significant morbidity associated
      with thyroid and parathyroid surgery. In the past decade, surgeons have
      increasingly used intraoperative neural monitoring (IONM) as an adjunct technique
      for localizing and identifying the RLN, detecting RLN injury, and predicting the
      outcome of vocal cord function. In recent years, many animal studies have
      investigated common pitfalls and new applications of IONM. For example, the use
      of IONM technology in animal models has proven valuable in studies of the
      electrophysiology of RLN injury. The advent of animal studies has substantially
      improved understanding of IONM technology. Lessons learned from animal studies
      have immediate clinical applications in establishing reliable strategies for
      preventing intraoperative RLN injury. This article gives an overview of the
      research progress on IONM-relevant animal models.

PMID- 27867862
TI  - Intermittent neural monitoring of the recurrent laryngeal nerve in surgery for
      recurrent goiter.
AB  - Reoperative thyroid surgery is still challenging even for skilled surgeons, and
      is associated with a higher incidence of complications, such as
      hypoparathyroidism and recurrent laryngeal nerve (RLN) palsy. Displacement of the
      RLN, scar tissue from previous neck surgery and difficulty in maintaining good
      hemostasis are risk factors in reoperations. The prevalence of RLN injury in
      reoperative thyroid surgery ranges as high as 12.5% for transient injury and up
      to 3.8% for permanent injury. Bilateral paresis can also occur during
      reoperations, and is a dangerous complication influencing the quality of life,
      sometimes requiring tracheostomy. RLN identification is the gold standard during
      thyroidectomy, and the use of intraoperative neuromonitoring (IONM) can be a
      valuable adjunct to visual identification. This technique can be used to identify
      the RLN and the external branch of the superior laryngeal nerve (EBSLN), both of
      which are standardized procedures. The aim of this review was to evaluate the use
      of intermittent neural monitoring of the RLN in surgery for recurrent goiter, and
      to assess the prevalence of RLN injury while using IONM reported in the current
      literature.

PMID- 27867863
TI  - Safety of energy based devices for hemostasis in thyroid surgery.
AB  - Energy based devices (EBD) have been developed, implemented and increasingly
      applied in thyroid surgery because they can provide a combined dissection and
      haemostatic effect. In particular, advantages of EBD have been described in terms
      of efficacious haemostasis, reduction of procedure-associated time, reduced
      incision length, less operative blood loss and transfusion need, decreased
      postoperative drain, pain and hospital stay. In addition, EBD are essential for
      endoscopic procedures. On the contrary, a potential drawback is the increased
      health care costs. This paper reviews relevant medical literature published on
      the safety of new devices for achieving hemostasis and dissection around the
      recurrent laryngeal nerve (RLN).

PMID- 27867864
TI  - BRAF V600E mutation in prognostication of papillary thyroid cancer (PTC)
      recurrence.
AB  - Papillary thyroid cancer (PTC) offers excellent prognosis, however relapse risk
      or persistent disease is related to ~30%. Currently, attention is paid to the
      possibility of patient group selection of different risk of unfavorable outcome
      to match a particular therapeutic approach. Therefore, interest in new prognostic
      and predictive markers known preoperatively is observed. BRAF V600E mutation is
      such a marker. Many studies analyzing the prevalence of the mutation and its
      relationship with other clinico-pathological risk factors were reported but with
      controversial conclusions. The prognostic significance of BRAF mutation was
      confirmed by some single centre studies, a few meta-analyses and a large
      multicenter retrospective international study. They confirmed a correlation
      between the mutation and the risk of recurrence. The strongest argument against
      using BRAF mutation as an independent prognostic and predictive factor in PTC is
      its high prevalence (30-80%). At present it seems that BRAF mutation is one of
      the factors influencing the prognosis and it should be analyzed in correlation
      with other prognostic factors. The most recent ATA recommendations do not
      indicate a routine application of BRAF status for initial risk stratification in
      differentiated thyroid cancer due to a lack of evident confirmation of a direct
      influence of mutation on the increase in relapse risk. However, ATA demonstrates
      the continuous risk scale for the relapse risk assessment, considering BRAF
      and/or TERT status. At present, researchers are working on determining the role
      of BRAF mutation in patients from a low-risk group and its correlations with
      others molecular events. Currently, BRAF mutation cannot be used as a single,
      independent predictive factor. However, its usefulness in the context of other
      molecular and clinico-pathological risk factors cannot be excluded. They may be
      used to make modern prognostic scales of relapse risk and be applied to
      individualized diagnostic and therapeutic strategy for PTC patients.

PMID- 27867865
TI  - Perioperative hemodynamic instability in patients undergoing laparoscopic
      adrenalectomy for pheochromocytoma.
AB  - Perioperative hemodynamic instability still remains the biggest surgical and
      anesthetic challenge in surgery for pheochromocytoma. The aim of this review was
      to discuss pre-, intra- and postoperative factors that may impact on hemodynamic
      condition of a patient. It describes patients' preparation with appropriate
      medication, principles of surgical technique as well as risk factors for
      development of hemodynamic instability in postoperative period. Currently the
      gold standard in the treatment of pheochromocytoma is preoperative use of alpha
      blockers and laparoscopic surgery. This approach allowed improving outcomes by
      lowering both mortality and morbidity.

PMID- 27867866
TI  - Indocyanine green-enhanced fluorescence for assessing parathyroid perfusion
      during thyroidectomy.
AB  - Identification of the parathyroid glands during thyroid surgery may prevent their
      inadvertent surgical removal and thus provide a better postoperative quality of
      life. Nevertheless, the most common "technique" for intraoperative evaluation of
      perfusion of parathyroid gland tissues during thyroid surgery is visual
      inspection of the physical condition of tissues, e.g., their color and bleeding
      edges. Another technique is measurement of intact parathyroid hormone. Recently,
      indocyanine green-enhanced fluorescence has been used in various surgical
      techniques, particularly laparoscopic surgery, to improve visualization and to
      provide detailed anatomical information. Fluorescent optical guidance helps
      surgeons to avoid inadvertent tissue injury while enhancing procedural
      efficiency. This technique has potential use for evaluating perfusion of the
      parathyroid gland in real-time intraoperative angiography.

PMID- 27867868
TI  - Innovative solutions in bariatric surgery.
AB  - Nowadays all over the world the rising plague of obesity can be observed. The
      obesity was recognized as "an epidemic of XXI century" in 1997 by World Health
      Organization. The change of eating habits, active lifestyle or pharmacological
      curation are often insufficient to fight against obesity. Nowadays, there are not
      any guidelines about gold standard for curing obese patients is bariatric
      surgery. At the moment, two types of bariatric procedures: laparoscopic Roux-en-Y
      gastric bypass and laparoscopic sleeve gastrectomy, are most commonly used. There
      are also some other new approaches, which are still being investigated. The
      mechanism of losing weight in bariatric surgery is based on restriction,
      malabsorption and neurohormonal effect. Not only is the surgery technique very
      important to succeed, but also the postoperative care in the outpatient clinic.
      This article reviews the new possibilities in obesity treatment.

PMID- 27867867
TI  - Early intact PTH (iPTH) is an early predictor of postoperative hypocalcemia for a
      safer and earlier hospital discharge: an analysis on 260 total thyroidectomies.
AB  - BACKGROUND: Hypocalcemia is the most frequent complication after thyroidectomy.
      Serum calcium levels are reliable only 48-72 hours postoperatively. Early intact
      PTH (iPTH) has been proposed as early predictor of postoperative hypocalcemia.
      Our aim is to assess the ability of iPTH in predicting postoperative
      hypocalcemia. METHODS: Two hundred and sixty patients underwent thyroidectomy
      with postoperative iPTH evaluation. The iPTH samplings were early performed after
      thyroidectomy. The calcium levels were dosed postoperatively. Age, sex, clinical
      diagnosis, obesity, comorbidities, previous neck surgery, preoperative therapy,
      type of surgery, dissectors used, lymphadenectomy, post-operative complications,
      reoperation and histological diagnosis were considered. The primary end-point was
      the postoperative hospital stay. The secondary end-points were serum calcium and
      iPTH. Three iPTH cut-offs were tested to assess which was the best value (10.0,
      15.0, and 20.0 pg/mL). RESULTS: The iPTH cut-off value of 10.0 pg/mL was the most
      accurate and specific for hypocalcemia. Comparing the iPTH value with the
      different values of calcium respectively 24 and 48 hours after surgery, a
      statistically stronger association with the serum calcium levels 48 hours
      postoperatively has been shown. iPTH >=10 pg/mL 3-6 hours after surgery was
      strongly correlated to early discharge. CONCLUSIONS: The correlation of iPTH with
      hypocalcemia is significant since a few hours after surgery and the value of iPTH
      >=10 pg/mL is able to select those patients for a safe and early discharge. The
      use of the iPTH might avoid unnecessary extensions of hospitalization.

PMID- 27867869
TI  - Thyroid Langerhans cell histiocytosis and papillary thyroid carcinoma.
AB  - A 27-year-old female, married with two children, presented to our clinic with a 1
      year history of thyroid swelling and pressure symptoms on lying backward and
      bilateral cervical lymphadenopathy. The patient was a known case of
      panhypopituitarism for 5 years. Comprehensive patient evaluation including FNAC
      with papillary thyroid cancer result then she underwent total thyroidectomy and
      bilateral neck dissection and final histologic examination confirmed papillary
      thyroid carcinoma in the background of lymphocytic thyroiditis, associated with
      Langerhans cell histiocytosis (LCH). The draining cervical lymph nodes were also
      involved by LCH and metastatic papillary thyroid carcinoma. Although the
      association of LCH with papillary thyroid carcinoma in the thyroid has been
      reported, their co-existence with LCH in the draining lymph nodes is very
      uncommon.

PMID- 27867870
TI  - Thyroid cancer with tracheal invasion: a pathological estimation.
AB  - We review the clinical and pathologic features of seven cases of papillary
      carcinoma of the thyroid that invaded the trachea and were treated by
      thyroidectomy, airway resection with reconstructive surgery over an interval of
      15 years. We depicted the peculiarity of invasion of well differentiated
      papillary thyroid carcinoma (PTC) cells is perpendicularly oriented to the
      tracheal lumen, in between cartilaginous rings, along blood vessels and collagen
      fibers. Tracheal rings appear non-infiltrated in all histological sections of
      well differentiated PTC infiltrating the trachea. Similar description of inter
      cartilage PTC infiltration into the trachea was first provided by Shin et al. in
      1993. Interestingly, our pathological revision support the estimation by Shin et
      al., though that cartilage rings infiltration did occur in poorly differentiated
      thyroid cancers with exiguous prognosis.

PMID- 27867871
TI  - Does being born low birth weight affect the ability to exercise?

PMID- 27867872
TI  - The rule of two-thirds in thyroid epidemiology.

PMID- 27867873
TI  - Prevalence and predictors of depression and anxiety in patients of diabetes
      mellitus in a tertiary care center.
AB  - BACKGROUND: Diabetes is one of the most common chronic diseases and affects
      virtually every organ of the human system. Depression and anxiety is common among
      patients with diabetes and associated with worse diabetes outcomes. AIMS AND
      OBJECTIVE: To study the prevalence and predictors of depression and anxiety in
      patients of Type 2 diabetes mellitus (T2DM) in Pt. B.D. Sharma, PGIMS, Rohtak,
      Haryana, India, a tertiary care center in Northern India. MATERIALS AND METHODS:
      Four hundred ten consecutive patients having T2DM and 410 healthy controls
      matched for age and sex attending the endocrine out-patient department of a
      tertiary care center of Northern India were included in the study.
      Sociodemographic and relevant clinical variables were collected. They were
      evaluated for depression and anxiety using Hamilton Depression Rating Scale and
      Hamilton Anxiety Rating Scale respectively. RESULTS: It was found that a
      significantly larger proportion of diabetic patients had depression (26.3% vs.
      11.2%, P = 0.001), anxiety (27.6% vs. 12.7%, P = 0.001) and comorbid depression
      and anxiety (21.0% vs. 7.3%, P = 0.001) as compared to healthy controls. Diabetic
      women had higher depression (17.1% vs. 9.3%) and anxiety (17.6% vs. 10.0%) than
      men. The major predictors for a severe form of depression and anxiety among T2DM
      cases were age, female sex, insulin therapy, retinopathy, nephropathy, and
      ischemic heart disease. CONCLUSION: The present findings reveal that diabetic
      cases had significantly higher depression and anxiety as compared to healthy
      controls. The risk factors for depression and anxiety were age, female sex,
      insulin therapy, and diabetic complications.

PMID- 27867874
TI  - Serum adiponectin levels in gestational diabetes mellitus.
AB  - INTRODUCTION: Gestational diabetes mellitus (GDM) is defined as any degree of
      glucose intolerance with onset or first recognition during pregnancy.[1]
      Pregnancy is a unique situation in which there is a physiological temporary
      increase in insulin resistance (IR). The mechanisms responsible for the
      gestational-induced IR are not completely understood. The current study was
      undertaken to compare adiponectin levels during 24-28 weeks period of gestation
      in drug-naive newly diagnosed GDM women with a cohort of normoglycemic pregnant
      women. SUBJECTS AND METHODS: A total of 47 pregnant women in the age group of 18
      40 years were included in this cross-sectional study, of which 13 were GDM cases
      and 34 were normoglycemic controls. Serum adiponectin level was analyzed by
      enzyme-linked immunosorbent assay. RESULTS: The mean adiponectin level was 16.92
      ng/ml (standard deviation [SD] = 2.78) and 19.38 ng/ml (SD = 2.71) in case and
      control groups, respectively, and the difference was found to be statistically
      significant (P = 0.008). CONCLUSION: Our study demonstrated decreased serum
      adiponectin levels in women with GDM when compared with age- and body mass index
      matched euglycemic pregnant women.

PMID- 27867875
TI  - Coronary artery calcium scoring is a better predictor of cardiac risk in
      subclinical hypothyroidism patients with low-risk Framingham score.
AB  - CONTEXT: Overt hypothyroidism accelerates the cardiovascular disease. Subclinical
      hypothyroidism (SCH), being considered as a preclinical state, impacts on
      cardiovascular status is not clear. AIMS: This study was aimed at assessing
      cardiac risk stratification by Framingham risk scoring (FRS) and coronary
      coronary artery calcium score (CACS) by noncontrast cardiac computed tomography
      in SCH. STUDY DESIGN: Observational study. SUBJECTS AND METHODS: We enrolled
      thirty treatment-naive SCH patients (aged 30-60 years with no serious concurrent
      medical conditions), thirty euthyroid (age, sex, and body mass index-matched)
      controls, and ten healthy controls. All cases were evaluated for coronary artery
      calcium scoring and Framingham risk score. STATISTICAL ANALYSIS: Qualitative data
      were analyzed using the Chi-square test. In addition, demographics and CACS are
      summarized graphically or in a table. RESULTS: SCH cases had higher
      thyroglobulin, while there was a trend toward an increase in total cholesterol,
      low-density lipoprotein (LDL), very LDL, and decrease in HDL levels. All
      participants had low-risk FRS (10-year FRS < 10%). The mean CACS in SCH was
      significantly higher than simple obese and healthy controls (47.17 vs. 2.67 vs.
      0.00). CONCLUSION: This study suggests that SCH is an independent risk factor for
      coronary artery disease in apparently healthy controls. The risk of occult
      coronary artery disease is increased in SCH cases.

PMID- 27867876
TI  - Prevalence and pattern of growth abnormalities in children with extrahepatic
      portal vein obstruction: Response to shunt surgery.
AB  - OBJECTIVE: Growth retardation is common in children with extrahepatic portal vein
      obstruction (EHPVO) and growth hormone (GH) resistance may play a dominant role.
      The aim of this study was to ascertain growth parameters and growth-related
      hormones in children with EHPVO, comparing with controls and to study the
      response of shunt surgery on growth parameters. MATERIALS AND METHODS: The
      auxological and growth-related hormone profile (GH; insulin-like growth factor
      binding protein-3 [IGFBP-3] and IGF-1) of thirty children with EHPVO were
      compared with controls. The effect of shunt surgery on growth parameters in 12
      children was also studied. RESULTS: The mean height standard deviation score
      (HSDS) of cases (-1.797 +/- 1.146) was significantly lower than that of controls
      (-0.036 +/- 0.796); the mean weight SDS of cases (-1.258 +/- 0.743) was also
      lower than that of controls (-0.004 +/- 0.533). The mean GH level of cases (5.00
      +/- 6.46 ng/ml) was significantly higher than that of controls (1.78 +/- 2.04
      ng/ml). The mean IGF-1 level of cases (100.25 +/- 35.93 ng/ml) was significantly
      lower as compared to controls (233.53 +/- 115.06 ng/ml) as was the mean IGFBP-3
      level (2976.53 +/- 1212.82 ng/ml in cases and 5183.28 +/- 1531.28 ng/ml in
      controls). In 12 patients who underwent shunt surgery, growth parameters
      significantly improved. CONCLUSIONS: Marked decrease in weight and height SDSs
      associated with GH resistance is seen in children with EHPVO, which improves with
      shunt surgery.

PMID- 27867877
TI  - Does one-to-one demonstration with insulin pads by health-care providers improves
      the insulin administration techniques among diabetic patients of a Tertiary Care
      Teaching Hospital in South India?
AB  - OBJECTIVES: The study was aimed to capture the effect of using injection pads as
      a tool in educating the diabetic patients who were on insulin. The attitude and
      practice of the patients in storage of insulin vials and disposal of insulin
      syringes were also assessed. MATERIALS AND METHODS: A facility based Quasi
      experimental study was carried out among the diabetic patients on insulin,
      attending diabetic clinic in endocrinology OPD in a tertiary care hospital,
      Puducherry. One to one intervention was given to the study participants or their
      attendants (who were involved in injecting insulin), by a trained investigator
      regarding all the steps of insulin administration. The insulin administration
      practices before and immediately after the intervention was assessed using a
      checklist. RESULTS: In total 91 patients were included for the study with mean
      (SD) age of 53.9 (10.6) years and of them 76% were females. The attitude and
      practices of the study participants, such as hand washing before handling
      insulin, checking the expiry date, storage of insulin, inspection of injection
      site, rolling and cleaning the vial, withdrawal of the syringe up to the required
      dose, pushing the plunger after inserting the syringe into the vial, checking and
      removal of air bubbles, cleaning the injection site and allow to dry and
      injection technique improved significantly after the intervention (P < 0.05).
      CONCLUSION: This study findings shows that using injection pads for educating
      patients helps them to practise better insulin administration. The findings from
      the study can be applied in routine care and has to be explored further in
      diabetic patient management.

PMID- 27867878
TI  - Prevalence of hypothalamo pituitary dysfunction in patients of traumatic brain
      injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) is common in young soldiers of armed
      forces leading to significant morbidity and mortality. We studied the prevalence
      of hypopituitarism following TBI and its association with trauma severity.
      MATERIALS AND METHODS: We conducted a 12-month prospective study of 56 TBI
      patients for the presence of hormonal dysfunction. Hormonal parameters were
      estimated during the early phase (0-10 days posttraumatically) and after 6 and 12
      months. Dynamic testing was done when required, and the results were analyzed by
      appropriate statistical methods. RESULTS: Hormonal dysfunction was seen in 39 of
      the 56 (70%) patients at initial assessment. Persisting pituitary deficiencies
      are seen in 7 and 8 patients at the end of 6 months and 12 months, respectively.
      Hypogonadotropic hypogonadism, hypothyroidism, and growth hormone deficiency are
      the most common diagnoses. Initial severe TBI and plurihormonal involvement
      predicted the long-term hypopituitarism. CONCLUSION: Early hypopituitarism was
      common in severe TBI, but recovers in majority. Evaluation for the occult
      pituitary dysfunction is required during the rehabilitation of TBI patients.

PMID- 27867879
TI  - Relationship of lean mass and obesity in Indian urban children and adolescents.
AB  - BACKGROUND: The association of obesity and lean mass (LM) has not been examined
      well in children and adolescents, and it remains controversial. OBJECTIVE: The
      objective of this study was to evaluate the relationship of body mass index (BMI)
      categories and regional obesity with total and regional LM in children and
      adolescents. METHODS: A total of 1408 children and adolescents (boys 58.9%; girls
      41.1%) divided according to BMI (normal weight 79.5%, overweight 16.0%, and obese
      4.5%) were included in this cross-sectional study. Total and regional LM and fat
      mass were measured by DXA. Leg and arm fat-to-total fat ratio (LATR) indicative
      of subcutaneous fat and trunk fat-to-total fat ratio (TTR), an indicator of
      visceral fat, were calculated. RESULTS: Mean age of the study population was 13.2
      +/- 2.7 years (boys - 13.0 +/- 2.7; girls - 13.4 +/- 2.8 years). Total LM (TLM)
      and its regional distribution were higher in overweight and obese groups when
      compared with those with normal BMI in both genders. TLM was comparable between
      overweight and obese in both genders. TLM per unit of fat progressively decreased
      from normal to obese categories. The difference in LM per unit fat between BMI
      categories persisted after adjustment for age, height, and sexual maturity score.
      TLM increased across the quartiles of TTR, but decreased with an increment in
      subcutaneous fat (quartiles of LATR). CONCLUSIONS: Obese children and adolescents
      apparently have higher LM than normal BMI children, but have lower LM per unit of
      fat. Subcutaneous fat had a negative impact and visceral fat had a positive
      impact on TLM.

PMID- 27867880
TI  - Effect of curative parathyroidectomy on insulin resistance.
AB  - BACKGROUND: Primary hyperparathyroidism (PHPT) is characterized by
      inappropriately elevated serum parathyroid hormone (PTH) level despite elevated
      serum calcium. Insulin resistant is the basic pathophysiology, behind the higher
      prevalence of diabetes mellitus in patients with PHPT. However, the improvement
      in insulin resistance (IR) after curative parathyroidectomy (CPTX) has not been
      established yet, as the study results are conflicting. MATERIALS AND METHODS: In
      this prospective interventional study, ten patients with mild PHPT (Group 1) and
      another ten patients with moderate to severe PHPT (Group 2) were undergone CPTX.
      The IR was assessed by homeostasis model assessment-IR (HOMA-IR), quantitative
      insulin sensitivity check index (QUICKI), fasting plasma glucose (FPG), and
      fasting serum insulin (FSI), before and 3 months after CPTX. RESULTS: There was
      no significant change of FPG and FSI, before and after CPTX in Group 1 (P = 0.179
      and P = 0.104) and Group 2 (P = 0.376 and P = 0.488). Before surgery, HOMA-IR was
      higher, and QUICKI was significantly lower, in both Group 1 (P = 0.058 and P =
      0.009) and Group 2 (P = 0.023 and P = 0.005) as compared to published normal
      reference mean, with no significant difference between the groups. Three months
      after surgery HOMA-IR increased further and QUICKI remained unchanged as compared
      to baseline, in both Group 1 (P = 0.072 and 0.082) and Group 2 (P = 0.54 and
      0.56), but statistically insignificant. CONCLUSION: IR remained unchanged after
      CPTX in mild as well as moderate to severe PHPT. Asymptomatic PHPT with abnormal
      IR should not be used as criteria for parathyroidectomy.

PMID- 27867881
TI  - Feasibility and acceptability of ambulatory glucose profile in children with Type
      1 diabetes mellitus: A pilot study.
AB  - BACKGROUND: Insulin administration and self-monitoring of blood glucose (SMBG)
      are pillars in the management of diabetes in children. Introduction of continuous
      glucose monitoring (CGM) has made it possible to understand the glycemic profiles
      which are not picked up by SMBG. Recent advent of flash glucose monitoring with
      inbuilt software to obtain ambulatory glucose profile (AGP) has emerged as a
      novel method to study glycemic patterns in adults with Type I diabetes. However,
      the use of AGP in children is yet to be explored. METHODS: AGP was used in 46
      children with Type 1 diabetes mellitus. Feasibility was measured regarding data
      and sensor failure. Acceptability was measured using a questionnaire. RESULTS:
      Forty-six children (22 girls and 24 boys) with a mean age of 10.07 years and mean
      diabetes duration of 3.4 years were included in the study. In this cohort, for 30
      (65.21%) subjects, the sensor remained in situ for a complete duration of 14
      days. Except for minor discomfort, AGP was well accepted by most of the children
      and their parents. CONCLUSION: AGP is a feasible option for monitoring glycemic
      status in children with diabetes with a high rate of acceptance.

PMID- 27867882
TI  - Prevalence of hypothyroidism in diabetic kidney disease and effect of thyroid
      hormone replacement on estimate glomerular filtration rate.
AB  - AIMS: To determine the prevalence of subclinical and overt hypothyroidism in
      diabetic kidney disease (DKD) and effect of thyroid hormone replacement on
      progression of DKD. MATERIALS AND METHODS: A prospective cohort study on 41 adult
      DKD patients who were screened for hypothyroidism. Hypothyroid DKD patients were
      started on levothyroxine replacement and were reviewed after 3 and 6 months.
      RESULTS: Of the total population, 14 (34.1%) cases were hypothyroid, among whom
      12 (29.3%) cases were subclinical, and 2 (4.8%) were overt hypothyroidism.
      Prevalence of hypothyroidism and mean thyroid stimulating hormone levels
      increased with increasing severity of DKD. There were 2 (14.3%) hypothyroid cases
      in stage 3b, 4 (28.5%) cases in stage 4, and 8 (57.2%) in stage 5 DKD. The mean
      estimate glomerular filtration rate (ml/min/1.73 m2) at baseline was 13.6 +/-
      13.3 which increased to 16.4 +/- 14.5 and 21.2 +/- 15.3 after 3 and 6 months of
      thyroid hormone replacement therapy (THRT), respectively (P < 0.001).
      CONCLUSIONS: Hypothyroidism is commonly associated with DKD. Prevalence of
      hypothyroidism increased with declining renal function. THRT significantly
      improved renal function in DKD patients with hypothyroidism after 3 and 6 months
      of therapy.

PMID- 27867883
TI  - Demographic details, clinical features, and nutritional characteristics of young
      adults with Type 1 diabetes mellitus - A South Indian tertiary center experience.
AB  - CONTEXT: Type 1 diabetes mellitus (T1DM) accounts for 5-10% of all diagnosed
      diabetes and the highest incidence is found in India. AIMS: The main objectives
      were to study the demographic, clinical, and nutritional characteristics of young
      adults with T1DM and its effect glycosylated hemoglobin levels. SUBJECTS AND
      METHODS: This cross-sectional study was conducted among young adults with T1DM
      (18-45 years of age) in a tertiary hospital in South India. Data were obtained
      from updated medical records. The dietary data were assessed from food diaries
      and 24 h recall method. Anthropometry was determined. RESULTS: The analysis
      revealed that socio-economic variables did not affect the glycosylated hemoglobin
      levels. The mean glycosylated hemoglobin value was 8.81 +/- 2.38%. Nearly, half
      the patients were malnourished. The overall dietary intake was inadequate. The
      multivariate regression model, adjusted for confounding factors such as gender,
      age, and body mass index, revealed that only duration of diabetes and protein
      intake were significant predictors of glycosylated hemoglobin status (P < 0.005).
      CONCLUSION: Integrated care provided at subsidized cost has been pivotal in
      effective diabetes management. However, there is an urgent need to educate our
      patients on nutrition therapy. T1DM patients need specialized advice to ensure
      appropriately balanced nutrition that has a significant impact on their long-term
      glycemic control.

PMID- 27867884
TI  - Comparison clinical and metabolic effects of metformin and pioglitazone in
      polycystic ovary syndrome.
AB  - INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common
      endocrine disorders in women. PCOS comprises a broad spectrum of anomalies,
      including hyperandrogenism, chronic anovulation, obesity, and infertility.
      Insulin resistance and its compensatory hyperinsulinemia play a key role in the
      pathogenicity of PCOS. This study compares the effects of 2 types of insulin
      sensitizer drugs, metformin and pioglitazone, on clinical, metabolic, and
      endocrine characteristics of women with PCOS. METHODS: In this randomized
      clinical trial, 56 women with PCOS (ages 20-49 years) were treated orally with
      either metformin (500 mg 3 times daily) or pioglitazone (30 mg daily) for 3
      months. Clinical (body weight, blood pressure [BP], and body mass index) and
      laboratory indices (fasting blood sugar [FBS], serum triglyceride [TG],
      cholesterol, low-density lipoprotein, high-density lipoprotein, insulin,
      testosterone, and dehydroepiandrosterone [DHEA]) were measured before and after
      therapy. Data were analyzed by Chi-square and McNemar's tests. RESULTS:
      Significant decreases were seen after treatment with metformin in extent of hair
      loss (P = 0.008), wrist circle (P = 0.011), weight (P = 0.047), diastolic BP (P =
      0.023), and DHEA (P = 0.035). A significant decrease in TG was seen with
      pioglitazone treatment (P = 0.047). In both groups, significant decreases in
      acne, menstrual disturbance, FBS, and serum insulin were seen. CONCLUSION: There
      is a significant amelioration of endocrine and metabolic indices with
      pioglitazone in PCOS patients. Although we were not able to recommend one
      treatment regime over the other, pioglitazone offers a useful, alternate
      treatment in women with PCOS who are not able to tolerate metformin.

PMID- 27867885
TI  - Trimester-specific reference interval for thyroid hormones during pregnancy at a
      Tertiary Care Hospital in Haryana, India.
AB  - BACKGROUND: Reference intervals for thyroid hormone during pregnancy need to be
      gestational age, method, and population specific and there is need to establish
      trimester-specific thyroid levels for the different population across the world.
      The aim of this study was to establish trimester-specific reference range for
      thyroid hormone during pregnancy in a tertiary care center in Haryana. MATERIALS
      AND METHODS: A total of 1430 pregnant women were recruited for the study.
      Participants having any history of chronic illness, goiter on physical
      examination, thyroid illness in the past or present, consuming thyroid
      medications, family history of thyroid illness, presence of anti-thyroid
      peroxidase antibody, poor obstetrics history were excluded from the study and
      reference population was identified to calculate serum free triiodothyronine
      (FT3), free thyroxine (FT4) and thyrotropin (TSH) for each trimester of
      pregnancy. RESULTS: The 2.5-97.5th percentiles for FT3, FT4, and TSH obtained in
      this study were 2.53-4.54 pg/ml, 0.88-1.78 ng/ml and 0.37-3.69 MUIU/ml in the
      first trimester, 2.0-4.73 pg/ml, 0.91-1.78 ng/ml and 0.54-4.47 MUIU/ml in the
      second trimester, 2.01-4.01 pg/ml, 0.83-1.73 ng/ml, and 0.70-4.64 MUIU/ml in the
      third trimester of pregnancy. Mean TSH increased and mean FT3 decreased
      significantly with the progression of gestational period. FT4 decreased from
      trimester 1-3rd, but the decrease was nonsignificant from 2nd to 3rd trimester.
      CONCLUSIONS: Existing results for trimester-specific reference intervals for
      thyroid hormones are inconsistent and cannot be extrapolated due to differences
      in ethnicity, maternal iodine status, laboratory assay method, and rigor for
      selection of reference population. Thus, establishment of reference intervals in
      each region is of great importance.

PMID- 27867886
TI  - Genotype-phenotype correlations of dyshormonogenetic goiter in children and
      adolescents from South India.
AB  - BACKGROUND: Dyshormonogenetic goiter is one of the most common causes of
      hypothyroidism in children and adolescents in iodine nonendemic areas. The exact
      genotype-phenotypic correlations (GPCs) and risk categorization of hypothyroid
      phenotypes of dyshormonogenetic mutations are largely speculative. The genetic
      studies in pediatric dyshormonogenesis are very sparse from Indian sub-continent.
      In this context, we analyzed the implications of TPO, NIS, and DUOX2 gene
      mutations in hypothyroid children with dyshormonogenetic hypothyroidism (DH) from
      South India. MATERIALS AND METHODS: This is interdisciplinary prospective study,
      we employed eight sets of primers and screened for 142 known single nucleotide
      polymorphisms in TPO, NIS, and DUOX2 genes. The subjects were children and
      adolescents with hypothyroidism due to dyshormonogenetic goiter. Congenital
      hypothyroidism, iodine deficiency, and Hashimoto's thyroiditis cases were
      excluded. RESULTS: We detected nine mutations in 8/22 (36%) children. All the
      mutations were observed in the intronic regions of NIS gene and none in TPO or
      DUOX2 genes. Except for bi-allelic, synonymous polymorphism of TPO gene in child
      number 14, all other mutations were heterozygous in nature. GPCs show that our
      mutations significantly expressed the phenotypic traits such as overt
      hypothyroidism, goiter, and existence of family history. Other phenotypic
      characters such as sex predilection, the age of onset and transitory nature of
      hypothyroidism were not significantly affected by these mutations. CONCLUSION:
      NIS gene mutations alone appears to be most prevalent mutations in DH among South
      Indian children and these mutations significantly influenced phenotypic
      expressions such as severity of hypothyroidism, goiter rates, and familial
      clustering.

PMID- 27867887
TI  - Cross-sectional study of nutritional markers in pregnancy.
AB  - OBJECTIVES: To note the value of serum Vitamin B12, folic acid, and ferritin in
      normal and high-risk pregnancies (HRPs) in patients attending antenatal clinic at
      All India Institute of Medical Sciences (AIIMS). MATERIALS AND METHODS: This is a
      cross-sectional study where a total of 282 patients attending Gynaecology
      Outpatient Department at AIIMS, New Delhi, India were recruited. Among the 282
      subjects, 251 were pregnant, and 31 were controls. The serum was tested for serum
      Vitamin B12, serum folic acid, and serum ferritin levels using Beckman Coulter
      Access 2 immunoassay. RESULTS: The median value of serum folic acid level in
      pregnant women was 12 pg/ml with range being 2-20 pg/ml in contrast to 8 pg/ml
      with range being 3-20 pg/ml in nonpregnant female. This difference was
      statistically significant. (P = 0.05). There was no significant difference in the
      median level of serum Vitamin B12 and serum ferritin in pregnant and nonpregnant
      group. Serum Vitamin B12 level was lower in the third trimester (127 pg/ml) than
      in first trimester (171 pg/ml) and the difference is statistically significant (P
      = 0.03). Serum ferritin levels were also significantly lower in the second
      trimester (16.4 pg/ml) than third trimester (24.55 pg/ml). Although the median
      serum folic acid level was lower in the first trimester (9.84 pg/ml) than in
      second trimester (10.8 pg/ml) and in the third trimester (13.18 pg/ml) but the
      difference was not statistically significant. There was no significant difference
      in Vitamin B12 level in HRPs (median value 134 pg/ml) as compared to low-risk
      pregnancies (149.5 pg/ml). CONCLUSION: Serum folic acid levels are significantly
      higher during pregnancy as compared to nonpregnant state. However, there was no
      significant difference in the median level of serum Vitamin B12 and serum
      ferritin in pregnant and nonpregnant group. Serum folic acid level and ferritin
      level were significantly higher in HRPs compared to low-risk pregnancies.

PMID- 27867888
TI  - Neck height ratio is an important predictor of metabolic syndrome among Asian
      Indians.
AB  - BACKGROUND AND AIMS: The predictive potential of neck circumference (NC) based
      indices (a measure of upper body fat distribution) for predicting metabolic
      syndrome (MetS) and its components among Indians is not known. This study aimed
      to evaluate the role of NC and neck height ratio (NHtR) as independent predictors
      of MetS and its components as compared to traditional anthropometric indices.
      MATERIALS AND METHODS: A total of 451 individuals from 867 screened individuals,
      30-80 years age, without any co-morbid state who gave informed written consent
      underwent clinical, anthropometric, and biochemical assessment. RESULTS: Patients
      with MetS in both the sexes had significantly higher NC, NHtR, glycated
      hemoglobin, fasting glucose, and dyslipidemia (higher triglycerides, total
      cholesterol/high-density lipoprotein cholesterol (HDL-C) ratio, low-density
      lipoprotein cholesterol/HDL-C ratio, and lower HDL-C). In both sexes, individuals
      in the highest tertile of NC had significantly greater central and generalized
      obesity, lower HDL-C, and significantly higher MetS. Receiver operating
      characteristic analysis revealed waist circumference (WC) to have the largest
      area under the curve for predicting MetS in both sexes, followed by NHtR, NC, and
      body mass index. NC and NHtR of >34.9 cm (sensitivity 78.6%; specificity 59.3%)
      and >21.17 cm/m (sensitivity 80.7% and specificity 64.6%) respectively for men
      and >31.25 cm (sensitivity 72.3%; specificity 64.4%) and >20.48 cm/m (sensitivity
      80.4% and specificity 60%) respectively for women were the best values for
      identifying MetS. Increased NC and NHtR had odds ratio of 1.52 (95% confidence
      interval [CI]: 1.37-1.68; P < 0.001) and 1.96 (95% CI: 1.67-2.29; P < 0.001)
      respectively in identifying MetS. CONCLUSION: NC and NHtR are good predictors of
      MetS and cardiovascular risk factors in Asian Indians. NHtR is reliable and
      perhaps an even better index than NC with regards to cardiovascular risk
      prediction.

PMID- 27867889
TI  - Liraglutide effect and action in diabetes-In (LEAD-In): A prospective
      observational study assessing safety and effectiveness of liraglutide in patients
      with type 2 diabetes mellitus treated under routine clinical practice conditions
      in India.
AB  - BACKGROUND: This 26-week, open-label observational study assessed the incidence
      and type of adverse events (AEs) associated with liraglutide use according to the
      standard clinical practice settings and the local label in India. MATERIALS AND
      METHODS: A total of 1416 adults with type 2 diabetes (T2D) treated with
      liraglutide in 125 sites across India were included in the study. Participants
      were newly diagnosed or already receiving antidiabetic medications. Safety and
      efficacy data were collected at baseline and at approximately weeks 13 and 26.
      The primary outcome was incidence and type of AEs while using liraglutide, with
      events classified by Medical Dictionary for Regulatory Activities system organ
      class and preferred term. The secondary objective was to assess other clinical
      parameters related to effective T2D management. RESULTS: Twenty AEs,
      predominately gastrointestinal, were reported in 1.3% of the study population in
      scheduled visits up to week 26. No serious AEs, including death, were reported.
      Hypoglycemic episodes were reported in 7.3% of participants at baseline and 0.7%
      at week 26. No major hypoglycemic events were reported up to week 26 (baseline:
      0.4%). Glycated hemoglobin was reduced from baseline (8.8 +/- 1.3%) to week 26 by
      1.6 +/- 1.1% (P < 0.0001); significant improvements in fasting blood glucose, and
      2-h postprandial blood glucose (post-breakfast, -lunch, and -dinner) were also
      observed. Mean body weight decreased by 8.1 +/- 6.5 kg from baseline (92.5 +/-
      14.6 kg; P < 0.0001). CONCLUSIONS: From the number of AEs reported, it is
      suggested that liraglutide was well tolerated in subjects with T2D treated under
      standard clinical practice conditions in India. Liraglutide was effective, and no
      new safety concerns were identified.

PMID- 27867891
TI  - Bangladesh national guidelines on the management of tuberculosis and diabetes
      mellitus co-morbidity (summary).
AB  - Tuberculosis (TB) and diabetes mellitus (DM) have synergetic relationship. People
      with diabetes are 2-3 times at higher risk of getting active TB disease. On the
      other hand, TB or anti-TB treatment may cause glucose intolerance. The dual
      disease of DM and TB is more likely to be associated with atypical disease
      presentation, higher probability of treatment failure and complications. In most
      of the health-care delivery systems of the world, DM and TB are managed
      separately by two vertical health-care delivery programs in spite of clear
      interaction between the two diseases. Thus, there should be a uniform management
      service for TB-DM co-morbidity. Realizing this situation, Bangladesh Diabetic
      Samity (BADAS), a nonprofit, nongovernment organization for the management of
      diabetes in Bangladesh, with the patronization of TB CARE II Project funded by
      U.S. Agency for International Development (USAID), launched a project in 2013
      titled BADAS-USAID TB Care II, Bangladesh with the goal of "Integrated approach
      to increase access to TB services for diabetic patients." One of the project
      objective and activity was to develop a national guideline for the management of
      TB-DM comorbidity. Thus, under the guidance of National Tuberculosis Control
      Program, of the Directorate General of Health Services, Government of the
      People's Republic of Bangladesh and World Health Organization (WHO), this
      guideline was developed in 2014. It is based on the existing "National Guidelines
      and Operational Manual for TB Control" (5th edition) and guidelines for
      management of DM as per WHO and International Diabetes Federations. Along with
      that, expert opinions from public health experts and clinicians and "Medline"
      searched literature were used to develop the guidelines. These guidelines
      illustrate the atypical presentation of the TB-DM co-morbidity, recommendations
      for screening, treatment, and follow-up of these patients and also
      recommendations in case of management of TB in patients with kidney and liver
      diseases. Thus, these guidelines will be a comprehensive tool for physicians to
      manage TB in diabetic patients.

PMID- 27867890
TI  - Bone turnover markers: Emerging tool in the management of osteoporosis.
AB  - Bone is a dynamic tissue which undergoes constant remodeling throughout the life
      span. Bone turnover is balanced with coupling of bone formation and resorption at
      various rates leading to continuous remodeling of bone. A study of bone turnover
      markers (BTMs) provides an insight of the dynamics of bone turnover in many
      metabolic bone disorders. An increase in bone turnover seen with aging and
      pathological states such as osteoporosis leads to deterioration of bone
      microarchitecture and thus contributes to an increase in the risk of fracture
      independent of low bone mineral density (BMD). These microarchitectural
      alterations affecting the bone quality can be assessed by BTMs and thus may serve
      as a complementary tool to BMD in the assessment of fracture risk. A systematic
      search of literature regarding BTMs was carried out using the PubMed database for
      the purpose of this review. Various reliable, rapid, and cost-effective automated
      assays of BTMs with good sensitivity are available for the management of
      osteoporosis. However, BTMs are subjected to various preanalytical and analytical
      variations necessitating strict sample collection and assays methods along with
      utilizing ethnicity-based reference standards for different populations.
      Estimation of fracture risk and monitoring the adherence and response to therapy,
      which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are
      the most important applications of measuring BTMs. This review describes the
      physiology of bone remodeling, various conventional and novel BTMs, and BTM
      assays and their role in the assessment of fracture risk and monitoring response
      to treatment with antiresorptive or anabolic agents.

PMID- 27867892
TI  - Fasting practices in Tamil Nadu and their importance for patients with diabetes.
AB  - Religious practices and cultural customs related to eating habits have a
      significant impact on lifestyle and health of the community. The Ramadan fasting
      in Muslims and its influence on various metabolic parameters such as diabetes
      have been reasonably studied. However, literature related to Hindu religious
      customs related to fasting and food patterns during various festivals and its
      effect on diabetes are scarce. This article is an attempt to describe the Hindu
      religious customs related to fasting and food practices from the State of Tamil
      Nadu (South India) and to raise the awareness among physicians about its
      relationship with diabetes which may help in managing their diabetic patients in
      a better way.

PMID- 27867893
TI  - Forum for Injection Technique 2.0 Addendum 1: Insulin use in indoor settings.
AB  - Insulin is a frequently used drug in the indoor setting. Comprehensive
      recommendations for best practice in insulin injection technique have been
      published by the forum for injection technique (FIT), India. This addendum
      focuses on insulin use in indoor settings, and complements the FIT 2.0
      recommendations. It discusses insulin use and disposal in critical care and
      noncritical care settings. It also highlights the need to ensure continuing
      nursing and medical education, and frame insulin policies for such use.

PMID- 27867894
TI  - Hyperthyroidism and Graves' disease: Is an ultrasound examination needed?
AB  - AIM: The aim of our study was to assess the limitation of clinical examination in
      determining the morphology of thyroid gland in patients with hyperthyroidism and
      its implications. METHODS: A retrospective analysis of consecutive patients with
      hyperthyroidism seen in a tertiary endocrine clinic were analyzed. Sub-analysis
      was performed on patients with proven Graves' disease. RESULTS: Of the 133
      patients included in this study with hyperthyroidism, 60 (45%) patients had
      significant nodularity on ultrasound (US). However, only 67% of these were
      identified on clinical examination. In patients with confirmed Graves' disease (n
      = 73), the discordance between US and clinical examination was very similar (18
      of 30 patients, 60%). CONCLUSION: US should form an essential part of the
      evaluation of hyperthyroidism as the morphology of thyroid gland could be
      variable and nodules in these glands would also need to be appropriately
      investigated. This would also significantly influence decision-making and
      appropriate immediate and follow-up management plan.

PMID- 27867895
TI  - Gender of rearing and psychosocial aspect in 46 XX congenital adrenal
      hyperplasia.
AB  - BACKGROUND: In congenital adrenal hyperplasia (CAH) with ambiguous genitalia,
      assigning gender of rearing can be complex, especially If genitalia is highly
      virilized. Apart from karyotype, prenatal androgen exposure, patient's gender
      orientation, sociocultural, and parental influences play a role. The aim of this
      study was to assess gender dysphoria and psychosocial issues in patients of CAH
      raised as males and females. MATERIALS AND METHODS: This is a cross-sectional
      study that includes patients (old and new) with CAH who were treated by us in the
      last 6 months. A semi-structured interview proforma was used to elicit history
      and psychosocial background of the patients. The clinical and biochemical details
      were noted. For psychological analysis, patients were screened for gender
      dysphoria using Parent Report Gender Identity Questionnaire for children <12
      years and Gender Identity/Gender Dysphoria Questionnaire for Adolescents and
      Adults. RESULTS: We analyzed 22 46 XX CAH patients among which, 3 were reared as
      males and 19 as females. Among the 19 patients reared as females, 17 patients
      showed no gender dysphoria. Two patients revealed gender dysphoria as indicated
      by their marginally low scores on the gender dysphoria assessment. However, in
      view of current literature and the age groups of the patients, behavior of the 6
      year-old patient can be best understood as being tomboyish. Gender dysphoria in
      the 22-year-old can be explained by the dominance of psychosocial factors and not
      hormones alone. Among the three patients reared as males, two prepubertal were
      satisfied with their male gender identity. The third patient, aged 32 years, had
      gender dysphoria when reared as a male that resolved when gender was reassigned
      as female and feminizing surgery was done. CONCLUSION: Gender assignment in 46 XX
      CAH is guided by factors such as degree of virilization of genitalia, gender
      orientation, patient involvement, sociocultural, and parental influences.

PMID- 27867896
TI  - Synchronous parathyroid adenoma and papillary thyroid cancer detected on 99mTc
      sestamibi scintigraphy.

PMID- 27867897
TI  - Current practice in treating adult female thalassemia major patients with
      hypogonadism: An International Network of Clinicians for Endocrinopathies in
      Thalassemia and Adolescence Medicine survey from Italy.

PMID- 27867898
TI  - Comments on: Microvascular and macrovascular complications in diabetes mellitus:
      Distinct or continuum?

PMID- 27867899
TI  - How prevalent are depression and anxiety symptoms in hypothyroidism?

PMID- 27867900
TI  - Reply to "How prevalent are depression and anxiety symptoms in hypothyroidism?"

PMID- 27867901
TI  - Sheehan's syndrome in two generations.

PMID- 27867902
TI  - Hypocalcemia and Fahr syndrome in a patient with Graves' disease: Difficult
      etiological diagnosis.

PMID- 27867903
TI  - Incretin Learning and Excellence Academy for Diabetes (iLEAD).

PMID- 27867904
TI  - Incremental role of 18F-fluorocholine PET/CT over technetium-99m-labeled MIBI
      scan in hyperparathyroidism.

PMID- 27867905
TI  - Multiple retroperitoneal paragangliomas.

PMID- 27867906
TI  - Hypercalcemia and electrocardiogram changes.

PMID- 27867907
TI  - Erratum: Sodium-glucose cotransporter 2 inhibitors with insulin in type 2
      diabetes: Clinical perspectives.
AB  - [This corrects the article on p. 22 in vol. 20, PMID: 26904465.].

PMID- 27867908
TI  - Erratum: Study of Vitamin B12 deficiency and peripheral neuropathy in metformin
      treated early Type 2 diabetes mellitus.
AB  - [This corrects the article on p. 631 in vol. 20, PMID: 27730072.].

PMID- 27867909
TI  - Prostate Cancer Screening: A Brief Tool to Incorporate Patient Preferences in a
      Clinical Encounter.

PMID- 27867911
TI  - [Communication and citizenship empowerment in health care: a case of action
      research in a polarized Venezuela].
AB  - An action-research project was implemented in Venezuela from 2009-2013 to empower
      social activists and patients in their fight against breast cancer (BC). The
      project was implemented in a context of high political and social polarization of
      the so-called "Bolivarian revolution". Based on an ecological perspective of
      health activism and communication, that encompasses the interpersonal, group and
      social levels, a series of activities were celebrated to develop the advocacy
      capabilities of citizens, especially women, expand the collaborative networks
      among different stakeholders, and promote a consensual view between social and
      institutional actors about a national response to fight BC. A horizontal and
      participatory communication allowed that the voice of usually marginalized actors
      was heard in the process of shaping health care policy.

PMID- 27867910
TI  - Intrinsically Disordered Side of the Zika Virus Proteome.
AB  - Over the last few decades, concepts of protein intrinsic disorder have been
      implicated in different biological processes. Recent studies have suggested that
      intrinsically disordered proteins (IDPs) provide structural plasticity and
      functional diversity to viral proteins that are involved in rapid replication and
      immune evasion in host cells. In case of Zika virus, the roles of protein
      intrinsic disorder in mechanisms of pathogenesis are not completely understood.
      In this study, we have analyzed the prevalence of intrinsic disorder in Zika
      virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein
      is enriched with intrinsically disordered protein regions (IDPRs) and this
      finding is consistent with previous reports on the involvement of IDPs in shell
      formation and virulence of the Flaviviridae family. We found abundant IDPRs in
      Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle
      formation and replication. In our view, the intrinsic disorder-focused analysis
      of ZIKV proteins could be important for the development of disorder-based drugs.

PMID- 27867913
TI  - Spontaneous Involution of Rathke's Cleft Cysts without Visual Symptoms.
AB  - BACKGROUND: There have been various reports in the literature regarding the
      conservative management of pituitary apoplexy, pituitary incidentalomas and
      Rathke cleft cysts (RCCs). However, to the best of our knowledge, spontaneous
      involution of cystic sellar mass has rarely been reported. We report 14 cases of
      cystic sellar masses with spontaneous involution. METHODS: A total of 14 patients
      with spontaneous regression of cystic sellar masses in our hospital were
      included. The median age was 35 years (range, 5-67), and 8 patients were male.
      Clinical symptoms, hormone study and MRI were evaluated for all patients. The
      initial MRI showed all 14 patients with RCCs. Eight patients were presented with
      sudden onset of headache, and 1 patient with dizziness. Another patient, a 5-year
      old child, was presented with delayed growth. Three patients had no symptoms via
      regular medical work up. All 14 patients had no visual symptoms. The follow-up
      period ranged from 5.7 to 42.8 months, with the mean of 17.3 months. RESULTS: The
      mean initial tumor size was 1.29 cm3 (range, 0.05 to 3.23). After involution, the
      tumor size decreased to 0.23 cm3 (range, 0 to 0.68) without any treatments.
      Repeated MRI showed a spontaneous decrease in tumor volume by 78% (range, 34 to
      99). The initial MRI showed that the tumor was in contact with the optic chiasm
      in 7 patients, while compressing on the optic chiasm in 3 patients. Five patients
      were initially treated with hormone replacement therapy due to hormone
      abnormality. After the follow-up period, only 2 patients needed a long-term
      hormone replacement therapy. CONCLUSION: The spontaneous involution of RCCs is
      not well quantified before. Their incidence has not been well demonstrated, but
      this phenomenon might be underreported. Conservative management can be a
      treatment option in some RCCs without visual symptoms, even in those that are
      large in size and in contact with the optic nerve via imaging study.

PMID- 27867914
TI  - Therapeutic Strategy for Cavernous Sinus-Invading Non-Functioning Pituitary
      Adenomas Based on the Modified Knosp Grading System.
AB  - BACKGROUND: Non-functioning pituitary adenomas (NFPA) invading into the cavernous
      sinus are surgically challenging. To decrease recurrence rate, surgeon makes a
      strong endeavor to resect tumor gross totally. However, gross total resection
      (GTR) is difficult to achieve with cavernous sinus invasion. Recently, a new
      classification system for cavernous invasion of pituitary adenomas was suggested.
      The aim of this study is to validate this new classification system and to
      identify limitations and considerations in designing treatment strategies for
      patients with NFPA involving the cavernous sinus. METHODS: Between January 2000
      and January 2012, 275 patients who underwent operation for NFPA were enrolled in
      the study. Median age was 50 years (15-79 years). There were 145 males and 130
      females. The median follow-up duration was 4 years (range 1-12.5 years). RESULTS:
      Related to extent of tumor removal, GTR was obtained in 184 patients (66.9%),
      near total resection (NTR) was obtained in 45 patients (16.3%), and sub-total
      resection (STR) was obtained in 46 patients (16.7%) of a total 275 patients.
      There were statistically significant differences between the extent of resection
      and the new Knosp classification (p<0.001). In the high-grade group of the new
      Knosp classification, there was no difference in recurrence between patients who
      underwent GTR or NTR only and those who underwent STR with adjuvant radiation
      therapy (p=0.515). CONCLUSION: In case of high risk of surgical complications,
      STR with adjuvant radiation therapy can be considered as an alternative strategy
      for safe treatment of cavernous-invading adenomas.

PMID- 27867912
TI  - Central Neurocytoma: A Review of Clinical Management and Histopathologic
      Features.
AB  - Central neurocytoma (CN) is a rare, benign brain tumor often located in the
      lateral ventricles. CN may cause obstructive hydrocephalus and manifest as signs
      of increased intracranial pressure. The goal of treatment for CN is a gross total
      resection (GTR), which often yields excellent prognosis with a very high rate of
      tumor control and survival. Adjuvant radiosurgery and radiotherapy may be
      considered to improve tumor control when GTR cannot be achieved. Chemotherapy is
      also not considered a primary treatment, but has been used as a salvage therapy.
      The radiological features of CN are indistinguishable from those of other brain
      tumors; therefore, many histological markers, such as synaptophysin, can be very
      useful for diagnosing CNs. Furthermore, the MIB-1 Labeling Index seems to be
      correlated with the prognosis of CN. We also discuss oncogenes associated with
      these elusive tumors. Further studies may improve our ability to accurately
      diagnose CNs and to design the optimal treatment regimens for patients with CNs.

PMID- 27867915
TI  - Surgical Resection of Non-Glial Tumors in the Motor Cortex.
AB  - BACKGROUND: Direct surgery to resect tumors in the motor cortex could improve
      neurological symptoms or cause novel motor weakness. The present study describes
      the neurological outcomes of patients after the surgical resection of non-glial
      tumors in the primary motor cortex. METHODS: The present study included 25
      patients who had pathologically confirmed non-glial tumors in the motor cortex
      for which they underwent surgery. Tumor location was verified using anatomical
      landmarks on preoperative magnetic resonance imaging scans. All surgeries
      involved a craniotomy and tumor resection, especially use of the sulcal
      dissecting approach for intra-axial tumors. RESULTS: Of the 25 patients, 10
      exhibited metastasis, 13 had a meningioma, and 2 had a cavernous malformation.
      Motor weakness and seizures were the most common symptoms, while 3 patients
      experienced only a headache. The tumor size was less than 20 mm in 4 patients, 20
      40 mm in 14, and greater than 40 mm in seven. Of the 25 patients, 13 exhibited
      motor weakness prior to the operation, but most of these symptoms (76.9%)
      improved following surgery. On the other hand, eight patients experienced
      seizures prior to the surgery, and in three of these patients (37.5%), the
      seizures were not controlled after the surgery. In terms of surgical
      complications, a postoperative hematoma developed in one of the meningioma
      patients, and the patient's hemiparesis was aggravated. CONCLUSION: The present
      findings show that careful and meticulous resection of non-glial tumors in the
      motor cortex can improve preoperative neurological signs, but it cannot
      completely control seizure activity.

PMID- 27867917
TI  - Health-Related Quality of Life in Brain Tumor Patients Treated with Surgery:
      Preliminary Result of a Single Institution.
AB  - BACKGROUND: Alongside the extent of removal and patients' survival in the
      management of brain tumors, health-related quality of life (HRQOL) has become an
      important consideration. The purpose of this study is to evaluate the change of
      HRQOL in brain tumor patients before and after surgery and to assess the
      associated factors that contribute to the change of HRQOL. METHODS: A total of
      258 patients who underwent surgical treatment were enrolled in this study. The
      European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire 30 (EORTC QLQ-C30) and the 20-item EORTC QLQ-Brain Neoplasm (QLQ
      BN20) were used to assess HRQOL. Patients were asked to fill out the
      questionnaires before and 3-6 months after surgery. RESULTS: Global QOL (p<0.001)
      and emotional function (p<0.018) were significantly improved after surgery.
      Physical function (p=0.015) was significantly aggravated. Among the symptoms,
      headache, pain and nausea and vomiting were significantly decreased (p<0.01,
      p=0.041, p<0.001, respectively), while dyspnea, communication deficit and
      weakness of the legs were increased (p=0.005, p=0.040, and p=0.014,
      respectively). Preoperative neurologic deficit (p=0.019) and tumor diameter
      (p=0.016) were significantly related to the patients who showed aggravation of
      global QOL after brain tumor surgery. In the aggravated global QOL group, common
      complaints and concerns included role function, appetite loss, financial
      difficulty and future uncertainty. CONCLUSION: In brain tumor patients, HRQOL has
      improved after surgery. Role function, appetite loss, financial difficulty and
      future uncertainty were important factors for HRQOL in brain tumor patients
      treated with surgery. Although there is National Health Insurance and Medical Aid
      program in Korea, financial difficulty and future uncertainty are much more
      important in influencing QOL than previously thought. The results of this short
      term follow up preliminary study suggest that several factors were related to
      HRQOL, Further research is needed to evaluate the long term change of HRQOL and
      enhance the global QOL by analyze related factors.

PMID- 27867920
TI  - Optimal Treatment Decision for Brain Metastases of Unknown Primary Origin: The
      Role and Timing of Radiosurgery.
AB  - BACKGROUND: Up to 15% of all patients with brain metastases have no clearly
      detected primary site despite intensive evaluation, and this incidence has
      decreased with the use of improved imaging technology. Radiosurgery has been
      evaluated as one of the treatment modality for patients with limited brain
      metastases. In this study, we evaluated the effectiveness of radiosurgery for
      brain metastases from unknown primary tumors. METHODS: We retrospectively
      evaluated 540 patients who underwent gamma knife radiosurgery (GKRS) for brain
      metastases radiologically diagnosed between August 1992 and September 2007 in our
      institution. First, the brain metastases were grouped into metachronous,
      synchronous, and precocious presentations according to the timing of diagnosis of
      the brain metastases. Then, synchronous and precocious brain metastases were
      further grouped into 1) unknown primary; 2) delayed known primary; and 3)
      synchronous metastases according to the timing of diagnosis of the primary
      origin. We analyzed the survival time and time to new brain metastasis in each
      group. RESULTS: Of the 540 patients, 29 (5.4%) presented precocious or
      synchronous metastases (34 GKRS procedures for 174 lesions). The primary tumor
      was not found even after intensive and repeated systemic evaluation in 10
      patients (unknown primary, 34.5%); found after 8 months in 3 patients (delayed
      known primary, 1.2%); and diagnosed at the same time as the brain metastases in
      16 patients (synchronous metastasis, 55.2%). No statistically significant
      differences in survival time and time to new brain metastasis were found among
      the three groups. CONCLUSION: Identification of a primary tumor before GKRS did
      not affect the patient outcomes. If other possible differential diagnoses were
      completely excluded, early GKRS can be an effective treatment option for brain
      metastases from unknown primary tumor.

PMID- 27867918
TI  - Clinical and Radiological Characteristics of Angiomatous Meningiomas.
AB  - BACKGROUND: Angiomatous meningioma is a rare histological subtype of meningioma.
      Therefore, this specific medical condition is rarely reviewed in the literature.
      In the present work, we report the clinical and radiological features with
      postoperative outcomes of angiomatous meningioma. METHODS: This retrospective
      study included the patients who were pathologically diagnosed with angiomatous
      meningioma after surgical resection between February 2010 and September 2015 in
      our institute. We analyzed the clinical data, radiological manifestation,
      treatment and prognosis of all patients. RESULTS: The 15 patients (5 males and 10
      females) were diagnosed with angiomatous meningioma during the study period. The
      median age of patients at the time of surgery was 63 years (range: 40 to 80
      years). According to Simpson classification, 7, 5, and 3 patients achieved
      Simpson grade I, II, and IV resection, respectively. In the follow-up period,
      recurrence was noted in one patient. Ten out of the 15 patients showed
      homogeneous enhancement. Two patients demonstrated cystic changes. There was no
      occurrence of calcification or hemorrhage in our patients. Characteristically, 14
      out of 15 patients showed signal voids of vessels. Significant peritumoral edema
      was observed in the majority of tumors (67%). CONCLUSION: Angiomatous meningiomas
      are rare benign meningioma. Brain images of angiomatous meningioma usually
      demonstrate signal void signs and peritumoral edema. In the present study,
      angiomatous meningiomas showed good prognosis after surgical resection.

PMID- 27867919
TI  - White Matter Change Revealed by Diffusion Tensor Imaging in Gliomas.
AB  - BACKGROUND: Tumor-related white matter change is detected at late stages with
      magnetic resonance imaging (MRI), when mass effect or prominent edema is present.
      We analyzed if diffusion tensor imaging (DTI) white matter change earlier than
      conventional MRI. METHODS: Twenty-six patients with gliomas (World Health
      Organization grade II, 5; grade III, 12; and grade IV, 9) within 2 cm from the
      posterior limb of the internal capsule (IC) were studied. Fifteen normal adults
      were enrolled as controls. Fluid attenuation inversion recovery MRI showed a high
      signal change at the posterior limb of the IC (HSIC) in 9 patients with grade III
      or IV gliomas. We classified the gliomas as WHO grade II (gliomas II), grade III
      or IV without HSIC [gliomas III/IV(-)] and grade III or IV with HSIC [gliomas
      III/IV(+)], as an indicator of the increase in the severity of the white matter
      changes. Fractional anisotropy (FA) and apparent diffusion coefficients (ADC)
      were calculated for the pyramidal tract. Tumor progression along pyramidal tract
      was evaluated by follow-up MRI in 16 patients at 40+/-18 months. RESULTS: FA
      showed no significant difference between gliomas II and control (p=0.694), but
      was lower in gliomas III/IV(-) and gliomas III/IV(+) (p<0.001). ADCs were higher
      in gliomas II, gliomas III/IV(-) and gliomas III/IV(+) than control (p<0.001).
      Tumor progression was detected in 2/16 patients. CONCLUSION: DTI detected white
      matter changes that appeared to be normal in MRI. ADC changed even in low grade
      glioma, indicating ADC may be a better parameter for the early detection of white
      matter change.

PMID- 27867921
TI  - Neurological Change after Gamma Knife Radiosurgery for Brain Metastases Involving
      the Motor Cortex.
AB  - BACKGROUND: Although Gamma Knife radiosurgery (GKRS) can provide beneficial
      therapeutic effects for patients with brain metastases, lesions involving the
      eloquent areas carry a higher risk of neurologic deterioration after treatment,
      compared to those located in the non-eloquent areas. We aimed to investigate
      neurological change of the patients with brain metastases involving the motor
      cortex (MC) and the relevant factors related to neurological deterioration after
      GKRS. METHODS: We retrospectively reviewed clinical, radiological and dosimetry
      data of 51 patients who underwent GKRS for 60 brain metastases involving the MC.
      Prior to GKRS, motor deficits existed in 26 patients (50.9%). The mean target
      volume was 3.2 cc (range 0.001-14.1) at the time of GKRS, and the mean
      prescription dose was 18.6 Gy (range 12-24 Gy). RESULTS: The actuarial median
      survival time from GKRS was 19.2+/-5.0 months. The calculated local tumor control
      rates at 6 and 12 months after GKRS were 89.7% and 77.4%, respectively. During
      the median clinical follow-up duration of 12.3+/-2.6 months (range 1-54 months),
      18 patients (35.3%) experienced new or worsened neurologic deficits with a median
      onset time of 2.5+/-0.5 months (range 0.3-9.7 months) after GKRS. Among various
      factors, prescription dose (>20 Gy) was a significant factor for the new or
      worsened neurologic deficits in univariate (p=0.027) and multivariate (p=0.034)
      analysis. The managements of 18 patients were steroid medication (n=10), boost
      radiation therapy (n=5), and surgery (n=3), and neurological improvement was
      achieved in 9 (50.0%). CONCLUSION: In our series, prescription dose (>20 Gy) was
      significantly related to neurological deterioration after GKRS for brain
      metastases involving the MC. Therefore, we suggest that careful dose adjustment
      would be required for lesions involving the MC to avoid neurological
      deterioration requiring additional treatment in the patients with limited life
      expectancy.

PMID- 27867916
TI  - Impact of Human Immunodeficiency Virus in the Pathogenesis and Outcome of
      Patients with Glioblastoma Multiforme.
AB  - BACKGROUND: Improvement in antiviral therapies have been accompanied by an
      increased frequency of non-Acquired Immune Deficiency Syndrome (AIDS) defining
      malignancies, such as glioblastoma multiforme. Here, we investigated all reported
      cases of human immunodeficiency virus (HIV)-positive patients with glioblastoma
      and evaluated their clinical outcomes. A comprehensive review of the molecular
      pathogenetic mechanisms underlying glioblastoma development in the setting of
      HIV/AIDS is provided. METHODS: We performed a PubMed search using keywords "HIV
      glioma" AND "glioblastoma," and "AIDS glioma" AND "glioblastoma." Case reports
      and series describing HIV-positive patients with glioblastoma (histologically
      proven World Health Organization grade IV astrocytoma) and reporting on HAART
      treatment status, clinical follow-up, and overall survival (OS), were included
      for the purposes of quantitative synthesis. Patients without clinical follow-up
      data or OS were excluded. Remaining articles were assessed for data extraction
      eligibility. RESULTS: A total of 17 patients met our inclusion criteria. Of these
      patients, 14 (82.4%) were male and 3 (17.6%) were female, with a mean age of
      39.5+/-9.2 years (range 19-60 years). Average CD4 count at diagnosis of
      glioblastoma was 358.9+/-193.4 cells/mm3. Tumor progression rather than AIDS
      associated complications dictated patient survival. There was a trend towards
      increased median survival with HAART treatment (12.0 vs 7.5 months, p=0.10).
      CONCLUSION: Our data suggests that HAART is associated with improved survival in
      patients with HIV-associated glioblastoma, although the precise mechanisms
      underlying this improvement remain unclear.

PMID- 27867922
TI  - Palliative Resection of Metastatic Brain Tumors Previously Treated by
      Stereotactic Radiosurgery.
AB  - BACKGROUND: Therapeutic approaches to brain metastases include surgery, whole
      brain radiotherapy, stereotactic radiosurgery (SRS), and combination therapy.
      Recently, postoperative or preoperative SRS draws more attention to reduce
      postoperative recurrence in brain metastases. The goal of this study is to review
      surgical outcome of patients who had been treated by SRS, and to discuss the
      effectiveness of preoperative SRS. METHODS: From 2009 to 2015, 174 patients were
      treated by SRS for brain metastases, and among these 50 patients underwent
      surgery. Eighteen patients underwent surgery after SRS, and 14 had
      oligometastases. The patients' median age at the time of surgery was 56 years
      (range, 34-84 years). The median follow-up duration was 16.5 months (range, 4-47
      months). Pathological findings were classified as follows; radiation necrosis
      (Group I, n=3), mixed type (Group II, n=2), and tumor-dominant group (Group III,
      n=9). We compared surgical outcome in respect of steroid, mannitol dosage,
      Karnofsky performance scale, and pathological subgroups. RESULTS: The median
      overall survival was 11 months (range, 2-40 months). Six, 12 and 24 months
      survival rate was 64.3, 42.9, and 28.6%, respectively. Improvement of Karnofsky
      performance score was achieved in 50% after surgery. The overall survival of
      Group I (26.6 months) was longer than the other groups (11.5 months).
      Additionally the patients were able to be weaned from medications, such as
      steroid administration after surgery was reduced in 10 cases, and mannitol dosage
      was reduced in 6 cases. Time interval within 3 months between SRS and surgery
      seemed to be related with better local control. CONCLUSION: Surgical resection
      after radiologically and symptomatically progressed brain metastases previously
      treated with SRS seems to be effective in rapid symptom relief and provides an
      improvement in the quality of life. A short time interval between SRS and
      surgical resection seems to be associated with good local tumor control.

PMID- 27867923
TI  - Failed First Craniotomy and Tumor Removal of Parasagittal Meningioma with Severe
      Peritumoral Brain Edema.
AB  - Parasagittal meningioma often presents as peritumoral brain edema (PTBE). The
      risk of edema increases when the tumor occludes the superior sagittal sinus
      (SSS). Although PTBE may be expected based on the patient's symptoms or
      radiologic findings, extensive brain swelling and extracranial herniation during
      elective surgery are rare. Herniation during surgery could lead to irreversible
      neurological damage and even brain rupture. We report a case of a failed routine
      craniotomy for a parasagittal meningioma with complete occlusion of the posterior
      third of the SSS in a 30-year-old male patient. The patient developed extensive
      brain swelling and extracranial herniation during surgery.

PMID- 27867925
TI  - A Stable Secondary Gliosarcoma with Extensive Systemic Metastases: A Case Report.
AB  - A 63-year-old man complained of intermittent motor weakness of his arm. The
      magnetic resonance image (MRI) of his brain displayed a high signal lesion in
      right cingulate gyrus on T2 weighted image. One year later, he showed a stuporous
      mental status with repeated seizures, and the follow-up brain MRI showed
      heterogeneously enhanced mass associated with bleeding. He was treated with
      surgery and radiotherapy for secondary glioblastomas in right cingulate gyrus.
      One year more later, a mass recurred on the left frontal base, and gliosarcoma
      was diagnosed. After tumor resection, ventriculoperitoneal shunt, chemotherapy,
      and re-radiation therapy, all brain lesions were stable. Fourteen months after
      the diagnosis of gliosarcoma, he complained of dyspnea and back pain. Torso
      positron emission tomography/computed tomography revealed multiple metastatic
      lesions in both lungs, pericardium, pleura, liver, lymph nodes, and bones, and
      metastatic gliosarcoma was diagnosed. One month later, the patient died because
      of the systemic metastases. We present an unusual case of secondary gliosarcoma
      with stable brain lesions and extensive systemic metastases.

PMID- 27867924
TI  - Metastatic Intracranial Hemangiopericytoma to the Spinal Column: A Case Report.
AB  - Intracranial hemangiopericytoma (HPC) is a rare brain tumor with aggressive
      biologic behavior associated with high recurrence rate and often with
      extracranial metastasis. The most common sites of extracranial metastasis of the
      intracranial HPC are the long bones, lung, liver and abdominal cavity in the
      order of frequencies. Extracranial metastases usually occur long after the
      initial diagnosis of the primary tumor. Metastatic intracranial HPC to the
      vertebra has been rarely reported. We present a case of intracranial HPC
      metastasized to the L2 vertebral body 13 years after multiple surgical resections
      and radiotherapy of the primary intracranial HPC.

PMID- 27867926
TI  - A Case of Solitary Brain Metastasis from Uterine Mullerian Adenosarcoma with
      Sarcomatous Overgrowth.
AB  - Uterine adenosarcoma (AS) are rare tumors and have more favorable outcomes than
      the aggressive uterine carcinosarcomas. Uterine adenosarcoma with sarcomatous
      overgrowth (ASSO) is a variant form of AS and exhibits aggressive growth of tumor
      and the prognosis is relatively poor compared with typical AS. Usually patterns
      of metastasis have been known to behave like endometrial carcinoma and spread
      through the lymphatics. Brain metastasis from uterine AS is extremely rare.
      Herein, we report a case of successfully surgically removed solitary brain
      metastasis without any extracranial recurrence from uterine ASSO after 4 years of
      primary treatment.

PMID- 27867927
TI  - Multiple Meningocerebral Metastasis and Extensive Skull Metastasis from Squamous
      Cell Carcinoma of Esophagus: A Case Report and Review of Literature.
AB  - Esophageal carcinoma rarely metastasizes to the brain. Although some studies have
      mentioned esophageal cancer with solitary brain metastasis or with
      meningocerebral metastasis or with skull metastasis, multiple meningocerebral
      metastasis and extensive skull metastasis from squamous cell carcinoma of
      esophagus has not been reported in the literature. We encountered a case of an
      extensive osteolytic change of the skull and multiple meningocerebral metastases
      from esophageal carcinoma.

PMID- 27867928
TI  - World Health Organization Grade II Oligodendroglioma Occurring after Successful
      Treatment for Childhood Acute Lymphoblastic Leukemia.
AB  - When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms
      are a significant long term problem. Radiation is generally accepted to be a
      major cause of the development of secondary neoplasms. Following treatment for
      ALL, a variety of secondary tumors, including brain tumors, hematologic
      malignancies, sarcomas, thyroid cancers, and skin cancers have been reported.
      However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we
      present a case of secondary oligodendroglioma occurring 13 years after the end of
      ALL treatment.

PMID- 27867929
TI  - Comparison of 3 and 7 Tesla Magnetic Resonance Imaging of Obstructive
      Hydrocephalus Caused by Tectal Glioma.
AB  - Obstructive hydrocephalus caused by tectal glioma, which relived by
      neuroendoscopy, have been described using 3.0 Tesla magnetic resonance imaging
      (3T MRI) so far, we present the results obtained from 3T and 7T MRI in this
      patient. A 21-year-old woman presented at our hospital with gait disturbance,
      hormonal insufficiency, and urinary incontinence that began prior to 6 years of
      age. 3.0T MRI revealed a non-enhancing tectal mass along with obstructive
      hydrocephalus. The mass measured approximately 1.1*1.0*1.2 cm. An endoscopic
      third ventriculostomy was performed to relieve the hydrocephalus. We compared
      hydrocephalus and cerebrospinal fluid (CSF) flow findings from 3T and 7T MRI,
      both preoperative and postoperative at 1, 6 months. Intraventricular CSF voiding
      on T2-weighted images obtained with 7T MRI showed greater fluid inversion than
      those obtained with 3T MRI. This study shows that 7T brain MRI can provide
      detailed information on hydrocephalus caused by tectal glioma. Further studies
      are needed to develop refined 7T MRI protocols for better images of
      hydrocephalus.

PMID- 27867930
TI  - A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a
      Child.
AB  - Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's
      lymphoma that is confined to the brain, eyes, and/or leptomeninges without
      evidence of a systemic primary tumor. Although the tumor can affect all age
      groups, it is rare in childhood; thus, its incidence and prognosis in children
      have not been well defined and the best treatment strategy remains unclear. A
      nine-year old presented at our department with complaints of diplopia, dizziness,
      dysarthria, and right side hemiparesis. Magnetic resonance image suggested a
      diffuse brain stem glioma with infiltration into the right cerebellar peduncle.
      The patient was surgically treated by craniotomy and frameless stereotactic
      guided biopsy, and unexpectedly, the histopathology of the mass was consistent
      with diffuse large B cell lymphoma, and immunohistochemical staining revealed
      positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for
      systemic lymphoma, but no evidence of lymphoma elsewhere in the body was
      obtained. In addition, she had a negative serologic finding for human
      immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL.
      She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination
      chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the
      tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.

PMID- 27867931
TI  - Seeding of Meningeal Sarcoma Along a Surgical Trajectory on the Scalp.
AB  - Primary sarcomas of the central nervous system are rare. These tumors is rapid
      growth often produces mass effect on the brain. Diagnosis is rendered
      pathologically after resection. Surgical resection is the mainstay treatment and
      need the adjuvant therapy. We report a 44-year-old female with a meningeal
      sarcoma of frontal meninges. She complained headache for 2 months and palpable
      forehead mass for 3 weeks. Brain MRI demonstrated a soft tissue mass sized as
      5.3*3.7*3.1 cm with well-defined osteolysis on the midline of the frontal bone.
      The mass attached to anterior falx without infiltration into the brain
      parenchyme. The tumor had extracranial and extraaxial extension with bone
      destruction. The tumor was totally removed with craniectomy and she had an
      adjuvant radiotherapy. However, an isolated subcutaneous metastasis developed at
      the both preauricular area of the scalp, originating from the scar which was
      remained the first surgery. After complete removal of this metastasis, she had an
      adjuvant radiotherapy in other hospital. However, she expired after six months
      after first surgery. We believe that the occurrence of tumor seeding at the site
      of incision in the scalp is related to using the fluid for irrigation after tumor
      resection and the same surgical instruments for the removal of the brain tumor.

PMID- 27867932
TI  - 2016 Canadian Association of Gastroenterology Educational Needs Assessment
      Report.

PMID- 27867933
TI  - Spatially Enabling the Health Sector.
AB  - Spatial information describes the physical location of either people or objects,
      and the measured relationships between them. In this article, we offer the view
      that greater utilization of spatial information and its related technology, as
      part of a broader redesign of the architecture of health information at local and
      national levels, could assist and speed up the process of health reform, which is
      taking place across the globe in richer and poorer countries alike. In making
      this point, we describe the impetus for health sector reform, recent developments
      in spatial information and analytics, and current Australasian spatial health
      research. We highlight examples of uptake of spatial information by the health
      sector, as well as missed opportunities. Our recommendations to spatially enable
      the health sector are applicable to high- and low-resource settings.

PMID- 27867934
TI  - A Comparison of Molecular Biology Mechanism of Shewanella putrefaciens between
      Fresh and Terrestrial Sewage Wastewater.
AB  - Municipal and industrial wastewater is often discharged into the environment
      without appropriate treatment, especially in developing countries. As a result,
      many rivers and oceans are contaminated. It is urgent to control and administer
      treatments to these contaminated rivers and oceans. However, most mechanisms of
      bacterial colonization in contaminated rivers and oceans were unknown, especially
      in sewage outlets. We found Shewanella putrefaciens to be the primary bacteria in
      the terrestrial sewage wastewater outlets around Ningbo City, China. Therefore,
      in this study, we applied a combination of differential proteomics, metabolomics,
      and real-time fluorescent quantitative PCR techniques to identify bacteria
      intracellular metabolites. We found S. putrefaciens had 12 different proteins
      differentially expressed in freshwater culture than when grown in wastewater,
      referring to the formation of biological membranes (Omp35, OmpW), energy
      metabolism (SOD, deoxyribose-phosphate pyrophosphokinase), fatty acid metabolism
      (beta-ketoacyl synthase), secondary metabolism, TCA cycle, lysine degradation (2
      oxoglutarate reductase), and propionic acid metabolism (succinyl coenzyme A
      synthetase). The sequences of these 12 differentially expressed proteins were
      aligned with sequences downloaded from NCBI. There are also 27 differentially
      concentrated metabolites detected by NMR, including alcohols (ethanol,
      isopropanol), amines (dimethylamine, ethanolamine), amino acids (alanine,
      leucine), amine compounds (bilinerurine), nucleic acid compounds (nucleosides,
      inosines), and organic acids (formate, acetate). Formate and ethanolamine show
      significant difference between the two environments and are possibly involved in
      energy metabolism, glycerophospholipid and ether lipids metabolism to provide
      energy supply, and material basis for engraftment in sewage. Because
      understanding S. putrefaciens's biological mechanism of colonization (protein,
      gene express, and metabolites) in terrestrial sewage outlets is so important to
      administering and improving contaminated river and to predicting and steering
      performance, we delved into the biological mechanism that sheds light on the
      effect of environmental conditions on metabolic pathways.

PMID- 27867935
TI  - Processing of Factor XII during Inflammatory Reactions.
AB  - The contact system was originally identified as an obsolete part of the
      coagulation system, but it has been repeatedly implicated in inflammatory states,
      such as infection, as well as in allergic- and chronic inflammatory disease.
      Under these conditions, there is surprisingly little evidence that factor XII
      (FXII) acts as a coagulation factor, and its activity appears to be mainly
      directed toward activation of the kallikrein-kinin system. The contact system
      factors interact with pathogens as well as cells of the (innate) immune system on
      several levels. Among others, these cells may provide negatively charged surfaces
      that contribute to contact activation as well as release enzymes that feed into
      this system. Furthermore, cellular receptors have been identified that bind
      contact factors at sites of inflammation. Based on the accumulated evidence, we
      propose a model for enzymatic crosstalk between inflammatory cells and the plasma
      contact system. During these reactions, FXII is enzymatically cleaved by non
      contact system enzymes. This generates unactivated FXII fragments that can
      subsequently be rapidly activated in the fluid phase. The resulting enzyme lacks
      procoagulant properties, but retains its pro-inflammatory characteristic as a
      prekallikrein activator.

PMID- 27867936
TI  - Effects of Lithium Monotherapy for Bipolar Disorder on Gene Expression in
      Peripheral Lymphocytes.
AB  - BACKGROUND: This study investigated the effect of lithium monotherapy on
      peripheral lymphocyte gene expression in bipolar disorder (BD). METHOD: Twenty
      two medication-free bipolar subjects (11 hypomanic, 11 depressed) were started on
      lithium monotherapy. Closely matched healthy subjects (n = 15) were included as
      controls but did not receive treatment. Blood RNA samples were collected at
      baseline and after 2 and 8 weeks of treatment. RNA expression was measured using
      the Affymetrix GeneChip(r) Human Gene 1.0 ST Array followed by Ingenuity pathways
      analysis. The results for the contrast of weeks 2 and 8 were not significantly
      different and were combined. RESULTS: In BD subjects, 56 genes showed significant
      (false discovery rate <0.1) expression changes from baseline; the effect sizes
      and directions for all of these were similar at weeks 2 and 8. Among these were
      immune-related genes (IL5RA, MOK, IFI6, and RFX2), purinergic receptors (P2RY14,
      P2RY2, and ADORA3) and signal transduction-related genes (CAMK1 and PIK3R6).
      Pathway and upstream regulator analysis also revealed that lithium altered
      several immune- and signal transduction-related functions. Differentially
      expressed genes did not correlate with week 8 clinical response, but other genes
      involved in protein synthesis and degradation did. CONCLUSION: Peripheral gene
      expression may serve as a biomarker of lithium effect.

PMID- 27867937
TI  - Dopamine D2L Receptor Is Required for Visual Discrimination and Reversal
      Learning.
AB  - The corticostriatothalamic circuit regulates learning behaviors via dopamine
      neurotransmission. D2 long (D2L) receptors are an isoform of dopamine D2
      receptors (D2Rs) and may act mainly at postsynaptic sites. It is well known that
      D2Rs influence high brain functions, but the roles of individual D2R isoforms are
      still unclear. To assess the influence of D2L receptors in visual discrimination
      learning, we performed visual discrimination and reversal tasks with D2L knockout
      mice using a touchscreen operant system. There were no significant differences in
      an operant conditioning task between genotypes. However, D2L knockout mice were
      impaired in both visual discrimination and reversal learning tasks. D2L knockout
      mice were also significantly slower than wild-type mice in collecting the reward
      in the visual discrimination task. These results indicate that D2L receptors play
      an important role in visual discrimination and reversal learning.

PMID- 27867938
TI  - A Mutation in NPAS3 That Segregates with Schizophrenia in a Small Family Leads to
      Protein Aggregation.
AB  - Schizophrenia and other major mental illnesses result from a complex interplay of
      genetic and environmental factors. We previously identified a mutation in NPAS3
      that results in a valine to isoleucine (V304I) amino acid substitution
      segregating with schizophrenia in a small family. The amino acid change occurs in
      a potentially critical region for protein function. Furthermore, the same amino
      acid substitution in proteins related to familial Alzheimer's disease and
      transthyretin amyloidosis has been associated with protein aggregation. In this
      study, we demonstrate that NPAS3 is prone to aggregation, and that the V304I
      mutation in NPAS3 increases this propensity in both bacterial and mammalian
      expression systems. We also show that NPAS3-V304I reduces soluble endogenous
      NPAS3, and increases insoluble endogenous NPAS3 and leads to alteration of
      transcriptional activity. These results suggest that protein aggregation,
      potentially leading to cell dysfunction via a loss of protein function through
      sequestration, may contribute to the pathogenesis of schizophrenia and other
      forms of mental illness. Further exploration of the mechanisms leading to
      abnormal protein quality control could lead to new therapeutic targets.

PMID- 27867939
TI  - A Rare Variant in CACNA1D Segregates with 7 Bipolar I Disorder Cases in a Large
      Pedigree.
AB  - Whole-genome sequencing was performed on 3 bipolar I disorder (BPI) cases from a
      multiplex pedigree of European ancestry with 7 BPI cases. Within CACNA1D, a gene
      implicated by genome-wide association studies, a G to C nucleotide transversion
      at 53,835,340 base pairs (bps) was found predicting the substitution of proline
      for alanine at amino acid position 1751 (A1751P). Using Sanger sequencing, the
      DNA variant was shown to co-segregate with the remaining 4 BPI cases within the
      pedigree. A high-resolution DNA denaturing curve method was then used to screen
      for the presence of the A1751P change in 4,150 BPI cases from the NIMH Genetics
      Initiative. The A1751P variant was found in 4 BPI cases. A second variant within
      exon 43, a C to T nucleotide transition, was found in 1 case at 53,835,355 bps,
      predicting the substitution of tryptophan for arginine at amino acid position
      1771 (R1771W). In the NHLBI Exome Sequencing Project database, the heterozygous
      A1751P variant was present in 3 of 4,300 subjects of European ancestry, and the
      R1771W change was not present in any subject. Given the rarity of these variants,
      large-scale case/control rare variant sequencing studies will be required for
      definitive conclusions.

PMID- 27867940
TI  - Oxytocin Receptor (OXTR) Methylation and Cognition in Psychotic Disorders.
AB  - Previous reports have identified an association between cognitive impairment and
      genetic variation in psychotic disorders. In particular, this association may be
      related to abnormal regulation of genes responsible for broad cognitive functions
      such as the oxytocin receptor (OXTR). Within psychotic disorders, it is unknown
      if OXTR methylation, which can have important implications for gene regulation,
      is related to cognitive function. The current study examined peripheral blood
      OXTR methylation and general cognition in people with schizophrenia,
      schizoaffective disorder, and psychotic disorder not otherwise specified (N =
      101). Using hierarchical multiple regression analysis, methylation at the
      Chr3:8767638 site was significantly associated with composite cognitive
      performance independent of demographic and medication factors while controlling
      for multiple testing in this combined diagnostic sample (adjusted p = 0.023).

PMID- 27867941
TI  - Familial Influences on Mismatch Negativity and Its Association with Plasma
      Glutamate Level: A Magnetoencephalographic Study in Twins.
AB  - Mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch
      negativity; MMNm) is regarded as a promising biomarker for schizophrenia.
      Previous electroencephalographic studies of MMN have demonstrated a moderate-to
      high heritability for MMN amplitudes. N-methyl-D-aspartate receptor-dependent
      glutamatergic neurotransmission is implicated in MMN generation. We hypothesized
      that the differences between identical twins in MMNm variables might be
      associated with differences in plasma levels of amino acids involved in
      glutamatergic neurotransmission. Thirty-three pairs of monozygotic (MZ) and 10
      pairs of dizygotic (DZ) twins underwent MMNm recording. The MMNm in response to
      tone duration changes, tone frequency changes, and phonemic changes was recorded
      using 204-channel magnetoencephalography. Of these, 26 MZ and 7 DZ twin pairs
      underwent blood sampling for determination of plasma amino acid levels. MMNm peak
      strength showed relatively high correlations in both MZ and DZ twin pairs. The
      differences in MMNm latencies tended to correlate with the differences in plasma
      amino acid levels within MZ pairs, while no significant correlation was observed
      after the Bonferroni correction. We observed a familial trait in MMNm strength.
      The differences in MMN latency in MZ twins might be influenced by changes in
      glutamate levels and glutamate-glutamine cycling; however, the results need to be
      replicated.

PMID- 27867942
TI  - Quantification of Calcified Particles in Human Valve Tissue Reveals Asymmetry of
      Calcific Aortic Valve Disease Development.
AB  - Recent studies indicated that small calcified particles observable by scanning
      electron microscopy (SEM) may initiate calcification in cardiovascular tissues.
      We hypothesized that if the calcified particles precede gross calcification
      observed in calcific aortic valve disease (CAVD), they would exhibit a regional
      asymmetric distribution associated with CAVD development, which always initiates
      at the base of aortic valve leaflets adjacent to the aortic outflow in a region
      known as the fibrosa. Testing this hypothesis required counting the calcified
      particles in histological sections of aortic valve leaflets. SEM images, however,
      do not provide high contrast between components within images, making the
      identification and quantification of particles buried within tissue extracellular
      matrix difficult. We designed a new unique pattern-matching based technique to
      allow for flexibility in recognizing particles by creating a gap zone in the
      detection criteria that decreased the influence of non-particle image clutter in
      determining whether a particle was identified. We developed this flexible pattern
      particle-labeling (FpPL) technique using synthetic test images and human carotid
      artery tissue sections. A conventional image particle counting method
      (preinstalled in ImageJ) did not properly recognize small calcified particles
      located in noisy images that include complex extracellular matrix structures and
      other commonly used pattern-matching methods failed to detect the wide variation
      in size, shape, and brightness exhibited by the particles. Comparative
      experiments with the ImageJ particle counting method demonstrated that our method
      detected significantly more (p < 2 * 10-7) particles than the conventional method
      with significantly fewer (p < 0.0003) false positives and false negatives (p <
      0.0003). We then applied the FpPL technique to CAVD leaflets and showed a
      significant increase in detected particles in the fibrosa at the base of the
      leaflets (p < 0.0001), supporting our hypothesis. The outcomes of this study are
      twofold: (1) development of a new image analysis technique that can be adapted to
      a wide range of applications and (2) acquisition of new insight on potential
      early mediators of calcification in CAVD.

PMID- 27867943
TI  - The evolution of surgical telementoring: current applications and future
      directions.
AB  - Surgical telementoring is a concept within telemedicine that involves the use of
      information technology to provide real-time guidance and technical assistance for
      surgical procedures from an expert physician at a different geographical
      location. It is a means to overcome the logistic obstacles associated with
      traditional mentoring and can aid in the distribution of advanced surgical
      techniques. In addition to its perceived educational benefits, it has the
      potential to directly impact patient care by providing immediate access to
      specialized surgical expertise in areas lacking access to qualified surgeons.
      With advances in technology, surgical telementoring has made significant strides
      in the past two decades and a breadth of positive experiences have been published
      in the literature. Despite this growth, questions remain regarding ideal
      videoconferencing methodology, resolution and latency requirements, security and
      liability issues, and telementoring in combination with emerging technology. This
      review addresses the history and progression, current applications, and future
      directions of surgical telementoring as a means to distribute advanced surgical
      expertise around the world.

PMID- 27867945
TI  - Surgical research using national databases.
AB  - Recent changes in healthcare and advances in technology have increased the use of
      large-volume national databases in surgical research. These databases have been
      used to develop perioperative risk stratification tools, assess postoperative
      complications, calculate costs, and investigate numerous other topics across
      multiple surgical specialties. The results of these studies contain variable
      information but are subject to unique limitations. The use of large-volume
      national databases is increasing in popularity, and thorough understanding of
      these databases will allow for a more sophisticated and better educated
      interpretation of studies that utilize such databases. This review will highlight
      the composition, strengths, and weaknesses of commonly used national databases in
      surgical research.

PMID- 27867946
TI  - Advances in fetal surgery.
AB  - Historically, the gold standard for the treatment of congenital malformations has
      been planned delivery at tertiary care center with attempted post-natal repair or
      amelioration of the lesion. Over the last few decades however, rapid advances in
      imaging and instrumentation technology combined with superior knowledge of fetal
      pathophysiology has led to the development of novel intrauterine interventions
      for most common fetal anomalies. Great success has already been seen the
      treatment of previous devastating anomalies such as myelomeningocele (MMC),
      congenital cystic malformations of the lung, twin-twin transfusion, and
      sacrococcygeal teratomas. Although still limited, these innovative techniques
      have unique potential to improve outcomes in the most devastating fetal
      anomalies.

PMID- 27867944
TI  - Advances in fluorescent-image guided surgery.
AB  - Fluorescence imaging is increasingly gaining intraoperative applications. Here,
      we highlight a few recent advances in the surgical use of fluorescent probes.

PMID- 27867947
TI  - Association of insulin treatment versus oral hypoglycaemic agents with diabetic
      retinopathy and its severity in type 2 diabetes patients in Cameroon, sub-Saharan
      Africa.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease
      associated with multiple macro and microvascular complications, diabetic
      retinopathy (DR) being the commonest one. Recent literature has reported an
      increased risk of DR with insulin use. METHODS: We carried out a cross-sectional
      study at the Ophthalmology Department of the Douala General Hospital (DGH) during
      a 2-year period to explore the association between insulin treatment and both DR
      and its severity as compared with oral hypoglycemic agents (OHAs) in Cameroonian
      T2DM patients aged >=35 years, and who were all screened for DR through eye
      examination including exhaustive retinal evaluation. RESULTS: In total, medical
      files of 134 T2DM patients were analyzed. The frequency of DR was 54.1% among
      patients on OHA and 73.9% among those on insulin treatment, giving an overall
      frequency of 57.5%. There were significantly more OHA treated patients than
      insulin treated patients (82.8% vs. 17.2%, P<0.001). As expected, both the OHA
      and insulin groups were comparable by age, sex, duration of diabetes, past
      history of hypertension, alcohol misuse, and current tobacco smoking. DR was
      almost significantly more frequent in T2DM patients under insulin regimen than in
      patients under OHA [73.9% vs. 54.1%; odds ratio (OR) 2.4; 95% confidence interval
      (CI), 0.9-6.6; P=0.06]. Proliferative diabetic retinopathy (PDR) was
      significantly more observed in insulin treated patients than in OHA treated
      patients (34.8% vs. 15.3%; OR 2.95; 95% CI, 1.1-8; P=0.035). Irrespective of
      staging, the frequency of diabetic macular edema (DME) was significantly higher
      in the insulin group than in the OHA group (43.5% vs. 19.8%; OR 3.1; 95% CI, 1.2
      8; P=0.019). CONCLUSIONS: Compared with OHA, insulin therapy may be associated
      with DR, DR severity and DME in these T2DM sub-Saharan African patients.

PMID- 27867948
TI  - Supra-therapeutic plasma concentrations of haloperidol induce moderate inhibition
      of lipopolysaccharide-induced interleukin-8 release in human monocytes.
AB  - BACKGROUND: The clinical use of antipsychotics and mood-stabilizing drugs with
      proven efficacy is largely determined by the occurrence of treatment-emergent
      adverse events and routine clinical chemistry and haematology data, which
      together define the safety and tolerability profile of these
      psychopharmaceuticals. Whereas the effects of mood-stabilizing drugs on
      functional properties of blood cells have been poorly investigated, the effects
      of antipsychotics have received more attention. Such studies have yielded
      conflicting results. This study examined the effects of the mood-stabilizing
      drugs carbamazepine and valproic acid and of the antipsychotic drugs olanzapine,
      risperidone and haloperidol on the production of the pro-inflammatory chemokine
      interleukin-8 (IL-8), which is released from human monocytes when activated by
      Gram-negative lipopolysaccharide (LPS). METHODS: Peripheral human whole blood was
      diluted with Roswell Park Memorial Institute (RPMI) cell culture medium and
      stimulated with LPS. Accumulating IL-8 was quantified in the supernatant with an
      adapted enzyme-linked immunosorbent assay (ELISA) and the results correlated to
      the number of monocytes at venipuncture. RESULTS: At supra-therapeutic
      concentrations of 100 uM, haloperidol inhibited the LPS-induced release of IL-8
      in peripheral human monocytes moderately, whereas olanzapine, risperidone,
      carbamazepine and valproic acid showed no such effect. CONCLUSIONS: The results
      suggest that these mood-stabilizing drugs and antipsychotics are endowed with
      clinically favorable inertness rather than pro-inflammatory properties.

PMID- 27867949
TI  - Continuous monitoring of the liver graft temperature: relationship between
      bacterial contamination of the perfusion fluid and early outcome.
AB  - BACKGROUND: A potential mechanism of the infection would be an infected donor,
      contamination at the time of the infusion and/or packaging, back-table procedure,
      and finally during the transplantation, all are potential sources of infection.
      The aim of our study is to analyze the incidence and significance of infection in
      the preservation solution according with the graft temperature. The second aim
      was to analyze the impact graft temperature on the clinical infections and the
      ischemia reperfusion injury. METHODS: Sixteen donors were prospectively included
      in this study, including 9 males and 7 females. The liver graft temperature
      monitoring shows variation in four different phases: at the harvesting beginning,
      before the graft packaging, at the beginning of the backtable, at the end of the
      backtable. RESULTS: There was no correlation between the functionality of the
      graft and the temperature of the perfusion fluid. CONCLUSIONS: In conclusion, we
      did not found a correlation between graft temperature, culture of the
      preservation solution and early post-transplant follow up.

PMID- 27867951
TI  - Red cell distribution width and cancer.
AB  - Red cell distribution width (RDW) is an index which primarily reflects impaired
      erythropoiesis and abnormal red blood cell survival. In last years the interest
      in this marker has considerably grown and now a lot of data are available
      indicating that this simple and inexpensive parameter is a strong and independent
      risk factor for death in the general population. Moreover, several investigations
      have been performed to investigate the role of RDW in cardiovascular and
      thrombotic disorders. Contrarily, there are relatively few reports focusing on
      RDW in the area of oncology and to date none review have been performed in this
      specific field. As such, the aim of this narrative review is to summarize some
      interesting results obtained in studies performed in patients affected by solid
      and hematological tumors. Even if larger studies are needed before these
      preliminary findings can be generalized, it seems plausible to affirm that RDW
      can be useful by adding prognostic information in patients with oncologic
      disease.

PMID- 27867953
TI  - Statistical description for survival data.
AB  - Statistical description is always the first step in data analysis. It gives
      investigator a general impression of the data at hand. Traditionally, data are
      described as central tendency and deviation. However, this framework does not fit
      to the survival data (also termed time-to-event data). Such data type contains
      two components. One is the survival time and the other is the status. Researchers
      are usually interested in the probability of event at a given survival time
      point. Hazard function, cumulative hazard function and survival function are
      commonly used to describe survival data. Survival function can be estimated using
      Kaplan-Meier estimator, which is also the default method in most statistical
      packages. Alternatively, Nelson-Aalen estimator is available to estimate survival
      function. Survival functions of subgroups can be compared using log-rank test.
      Furthermore, the article also introduces how to describe time-to-event data with
      parametric modeling.

PMID- 27867950
TI  - Review: capsule colonoscopy-a concise clinical overview of current status.
AB  - The colon capsule endoscopy (CCE) was first introduced in 2007. Currently, the
      main clinical indications for CCE are completion of incomplete colonoscopy, polyp
      detection and investigation of inflammatory bowel disease (IBD). Although
      conventional colonoscopy is the gold standard in bowel cancer screening,
      incomplete colonoscopy remains a problem as lesions are missed. CCE compares
      favourably to computer tomography colonography (CTC) in adenoma detection and has
      therefore been proposed as a method for completing colonoscopy. However the data
      on CCE remains sparse and current evidence does not show its superiority over CTC
      or conventional colonoscopy in bowel cancer screening. CCE also seems to show
      good correlation with conventional colonoscopy when used to evaluate IBD, but
      there are not many published studies at present. Other significant limitations
      include the need for aggressive bowel preparation and the labour-intensiveness of
      CCE reading. Therefore, much further software and hardware development is
      required to enable CCE to fulfill its potential as a minimally-invasive and
      reliable method of colonoscopy.

PMID- 27867952
TI  - Critical laboratory values communication: summary recommendations from available
      guidelines.

PMID- 27867954
TI  - Laparoscopic repair of inguinal hernia in adults.
AB  - Laparoscopic repair of inguinal hernia is mini-invasive and has confirmed
      effects. The procedures include intraperitoneal onlay mesh (IPOM) repair,
      transabdominal preperitoneal (TAPP) repair and total extraperitoneal (TEP)
      repair. These procedures have totally different anatomic point of view, process
      and technical key points from open operations. The technical details of these
      operations are discussed in this article, also the strategies of treatment for
      some special conditions.

PMID- 27867955
TI  - A new technique to repair huge tracheo-gastric fistula following esophagectomy.
AB  - We reported the management of a life-threatening condition as a large tracheo
      gastric fistula involved the carina, the left and the right bronchus that
      complicated Ivor Lewis esophagogastrectomy for esophageal cancer. An urgent right
      thoracotomy was performed and the tracheal defect was covered with a reversed
      pedicled pericardial patch reinforced with an intercostal muscle flap. Cervical
      esophagostomy and a feeding jejunostomy completed the operation. Five months
      later, the continuity of gastrointestinal tract was restored using a transverse
      colon.

PMID- 27867956
TI  - The impact of unemployment on cancer mortality, and how to avoid it.

PMID- 27867957
TI  - Corin as novel biomarker for myocardial infarction.

PMID- 27867958
TI  - Does AQuIRE challenge the role of navigational bronchoscopy for peripheral
      pulmonary lesions?

PMID- 27867959
TI  - Genesis on diamonds II: contact with diamond enhances human sperm performance by
      300.

PMID- 27867960
TI  - Is a short anesthetic exposure in children safe? Time will tell: a focused
      commentary of the GAS and PANDA trials.
AB  - Early life exposure to general anesthesia in preclinical studies has consistently
      led to permanent cognitive deficits later in life. However, the extent to which
      this finding is translatable to humans is the subject of much debate as the
      results from clinical studies have been mixed. Recently two well-designed
      clinical trials have attempted to add clarity to our murky understanding. The
      General Anesthesia compared to Spinal anesthesia (GAS) trial, was an
      international, prospective, randomized, multicenter, equivalence trial comparing
      infants undergoing herniorrhaphy receiving general anesthesia vs. neuraxial
      anesthesia. The results released are from a pre-determined secondary outcome of a
      behavioral/developmental assessment of 2 years old that found equivalence between
      the two groups. The Pediatric Anesthesia NeuroDevelopment Assessment (PANDA)
      trial was an ambi-directional cohort trial, comparing patients receiving general
      anesthesia for hernia repair before 3 years old vs. sibling-matched controls. The
      neuropsychological battery performed showed no difference between siblings. Taken
      together, there is cautious optimism that short anesthesia exposure may not lead
      to significant cognitive decline in humans, but one should also consider that the
      GAS trial has yet to release the primary endpoint, IQ testing at age 5, and the
      PANDA trial may not represent the general population given the high socioeconomic
      status and high control IQ scores. Furthermore, as seen in preclinical studies,
      the cognitive deficit might not be significant until later in life, and longer
      exposures to anesthesia may have a more deleterious effect on cognitive function.
      While these new studies greatly increase our understanding in humans, there are
      many more questions that need to be addressed.

PMID- 27867961
TI  - Cardio-renal protection with empagliflozin.
AB  - Cardiovascular (CV) and kidney disease are common and significant complications
      in people with type 2 diabetes (T2DM). CV disease is the leading cause of death,
      morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney
      disease is a major risk factor for CV disease and is the main reason why patients
      need renal replacement therapy. In this perspective, we highlight the results of
      the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a
      member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose
      lowering medications, reduces death from CV causes, hospitalisation for heart
      failure and progression to end stage kidney disease in patients with T2DM and
      established CV disease. The SGLT2 receptor mediates high-capacity glucose uptake
      in the early proximal tubule, and SGLT2 inhibitors, via their ability to promote
      glycosuria, have been developed as glucose lowering medications. As well as
      having a glucose lowering effect, SGLT-2 inhibitors also reduce blood pressure,
      promote weight loss and reduce uric acid levels. Potential side-effects or
      concerns related to the use of SGLT-2 inhibitors include increased rates of
      urinary tract infections, genital tract infections, postural hypotension,
      diabetic ketoacidosis, acute kidney injury and possible increased rates of
      fractures. The exact mechanisms that result in empagliflozin's dramatic CV and
      renal protective effects, with a very favourable safety/tolerability profile, in
      the EMPA-REG study remain to be fully defined. However, they are most likely
      distinct from the glucose lowering effects of empagliflozin. CV safety trials
      involving dapagliflozin and canagliflozin, members of the SGLT-2 class, are under
      way and the results from these studies will help to answer the question as to
      whether the cardio-renal benefits of empagliflozin are a class-effect or not.
      Without doubt, trials to investigate whether SGLT-2 inhibitors have cardio-renal
      protective effects in patients without diabetes will start soon.

PMID- 27867962
TI  - Tricuspid valve-in-valve implantation for failing bioprosthetic valves: an
      evolving standard of care.
AB  - Redo surgery for bioprosthetic tricuspid valve failure is associated with high
      morbidity and mortality. In recent years, transcatheter tricuspid valve-in-valve
      (VIV) therapy utilizing ballon-expandable transcatheter valves has become
      available. The tricuspid Valve-in-Valve International Data (VIVID) registry
      initial results represent the largest experience with tricuspid VIV therapy,
      demonstrating high procedural success rates with low 30 days mortality and
      excellent survival free of repeat tricuspid intervention in 1 year. Although
      longer clinic and hemodynamic follow-up will be needed to fully understand the
      role of this therapy, these data support the safety, feasibility and beneficial
      effects of tricuspid VIV therapy. For patients with bioprosthetic tricuspid valve
      failure, tricuspid VIV is likely to become a first-line treatment option.

PMID- 27867963
TI  - alphavbeta1 integrin as a novel therapeutic target for tissue fibrosis.
AB  - Chronic tissue injury with fibrosis results in disruption of tissue architecture,
      organ dysfunction and eventually organ failure. Currently, therapeutic options
      for tissue fibrosis are severely limited and organ transplantation including high
      cost and co-morbidities is the only effective treatment for end-stage fibrotic
      disease. Therefore, it is imperative to develop effective anti-fibrotic agents.
      Integrins are transmembrane proteins and are major receptors for cell
      extracellular matrix (ECM) and cell-cell adhesion. Modulation of these molecules,
      particularly alphav integrin family, has exhibited profound effects on fibrosis
      in multiple organ and disease state. Based on the several studies, the integrins
      alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 have been known to
      modulate the fibrotic process via activation of latent transforming growth factor
      (TGF)-beta in pre-clinical models of fibrosis. In this perspective, we reviewed
      the functions of alphavbeta1 integrin as a potentially useful target molecule for
      antifibrotic agent and introduced novel specific small-molecule inhibitors
      targeting this integrin.

PMID- 27867965
TI  - Coronary artery bypass grafting (CABG) alone in moderate ischemic mitral
      regurgitation: is CABG really enough?

PMID- 27867964
TI  - An electromechanical hug for the failing heart.

PMID- 27867966
TI  - How much clinical evidence is enough: regulation of medical devices?

PMID- 27867967
TI  - Fatty acid binding proteins as biomarkers of disease severity and response to
      treatment in severe pneumonia required admission to intensive care unit.

PMID- 27867968
TI  - Implications of obesity in exceptional longevity.

PMID- 27867969
TI  - The hunt for fatal myocardial infarction biomarkers: predictive circulating
      microRNAs.

PMID- 27867970
TI  - Acquisition of carbapenem-resistant Acinetobacter baumannii in the intensive care
      unit: just a question of time?

PMID- 27867971
TI  - Another promise against ischemia reperfusion injury: every success raises new
      questions.

PMID- 27867972
TI  - Live-attenuated vaccination increases the diversity of pathogen-specific T cell
      repertoire triggered in chronic infection responses.

PMID- 27867973
TI  - Immunotherapy in small-cell lung cancer: at what point are we?

PMID- 27867974
TI  - Is macitentan not a treatment option for digital ulcers in systemic sclerosis?

PMID- 27867975
TI  - The AMPK-SKP2-CARM1 axis links nutrient sensing to transcriptional and epigenetic
      regulation of autophagy.

PMID- 27867976
TI  - Sofosbuvir and velpatasvir: a stellar option for patients with decompensated
      hepatitis C virus (HCV) cirrhosis.

PMID- 27867977
TI  - Immune checkpoint inhibition in patients with brain metastases.

PMID- 27867978
TI  - Osteoporosis and strontium-substituted hydroxyapatites.

PMID- 27867980
TI  - C-WORTHY: the beginning of the rise of elbasvir and grazoprevir for the treatment
      of hepatitis C genotype 1 mono and HIV co-infected patients.

PMID- 27867979
TI  - Na+ homeostasis by epithelial Na+ channel (ENaC) and Nax channel (Nax):
      cooperation of ENaC and Nax.

PMID- 27867981
TI  - Grazoprevir plus elbasvir and other treatment options in hepatitis C infected
      patients with stage 4-5 chronic kidney disease.

PMID- 27867982
TI  - ASSURE vs. S-TRAC: conflicting results of adjuvant treatments for kidney cancer
      in the era of targeted agents and genomics.

PMID- 27867983
TI  - A liberal glycemic target in critically ill patients with poorly controlled
      diabetes?

PMID- 27867984
TI  - Can xerostomia be further reduced by sparing parotid stem cells?

PMID- 27867985
TI  - Transapical beating-heart mitral valve repair using a cordal implantation device
      are we ready to open our minds?

PMID- 27867986
TI  - The role of glutamate transport and SLC7A11 expression in tumor-associate
      seizures and survival in patients with malignant gliomas.

PMID- 27867987
TI  - Modifying therapy in patients with advanced Hodgkin's lymphoma by integrating
      early metabolic response by interim PET-CT.

PMID- 27867988
TI  - A canine model for neuronal ceroid lipofuscinosis highlights the promise of gene
      therapy for lysosomal storage diseases.

PMID- 27867989
TI  - The Ross procedure is under-used although long-term results show superior results
      to those obtained following mechanical aortic valve replacement.

PMID- 27867990
TI  - Hospital-acquired pneumonia and community-acquired pneumonia: two guys?

PMID- 27867991
TI  - Connecting enterovirus infection to dystrophin dysfunction in dilated
      cardiomyopathy.

PMID- 27867992
TI  - Tumor vaccines and cellular immunotherapies.

PMID- 27867993
TI  - Measuring soluble CD40 ligand: it is a fancy prognostic biomarker in STEMI
      patients?

PMID- 27867994
TI  - The case for preoperative aspirin administration in patients undergoing elective
      CABG: is it open or closed?

PMID- 27867995
TI  - Interventional therapies in ischemic ventricular dysfunction: facts and versions!

PMID- 27867996
TI  - Towards a cure for Fibrodysplasia ossificans progressiva.

PMID- 27867998
TI  - Circulating micro ribonucleic acids in cardiovascular disease: a look beyond
      myocardial injury.

PMID- 27867997
TI  - Narcolepsy and influenza vaccination-the inappropriate awakening of immunity.

PMID- 27867999
TI  - Afatinib plus chemotherapy versus chemotherapy alone after progression on
      afatinib: new insights on old question?

PMID- 27868000
TI  - Rhythm is a dancer: the immediate management of postoperative atrial fibrillation
      following cardiac surgery.

PMID- 27868001
TI  - Branching pattern of the lateral femoral cutaneous nerve at the proximal thigh: a
      commentary on a recent published cadaveric study.

PMID- 27868002
TI  - Continuing aspirin before coronary artery bypass grafting surgery: old fears
      challenged by new evidences.

PMID- 27868003
TI  - The prostate-specific protein, transglutaminase 4 (TG4), is an autoantigen
      associated with male subfertility.

PMID- 27868004
TI  - Should trochanteric osteotomy be always avoided during safe hip dislocation?

PMID- 27868005
TI  - The anterolateral ligament: a closed chapter?

PMID- 27868006
TI  - Circulating fibrocytes serve as a marker for clinical diagnosis.

PMID- 27868007
TI  - Robotics accuracy in orthopaedics: is it enough for a well-working knee
      replacement?

PMID- 27868008
TI  - Robotic unicondylar knee arthroplasty: a commentary on a recently published level
      1 study.

PMID- 27868009
TI  - The potential of anti-VEGF (Vasotide) by eye drops to treat proliferative
      retinopathies.

PMID- 27868010
TI  - The emerging role of sST2 blocking in the therapy of graft-versus-host disease.

PMID- 27868011
TI  - Time to progression ratio: promising new metric or just another metric?

PMID- 27868012
TI  - PTK2/FAK: a new predictive biomarker for response to radiotherapy in head and
      neck squamous cell carcinoma.

PMID- 27868013
TI  - Azoramide: a new drug for the treatment of type 2 diabetes?

PMID- 27868014
TI  - Severe ischemic cardiomyopathy-a new answer in management?

PMID- 27868015
TI  - Vasopressin versus noradrenaline as initial therapy in septic shock. Is
      vasopressin-related renal protection doomed to "vanish" in the haze?

PMID- 27868016
TI  - Statins barely touch the heart but bite the kidneys after cardiac surgery.
      Coenzyme Q10 deficiency in the dock?

PMID- 27868017
TI  - Less invasive approach in knee arthroplasty: everybody on board?

PMID- 27868018
TI  - Collagen and fibronectin: threads linking obesity and breast cancer.

PMID- 27868019
TI  - Playing with nanoparticle shapes and laser powers to decide which route to take
      during photothermal therapy: apoptosis or necrosis?

PMID- 27868020
TI  - Hybrid approach to multivessel coronary artery disease: a commentary.

PMID- 27868021
TI  - Rational for targeting the hedgehog signalling pathway in acute myeloid leukemia
      with FLT3 mutation.

PMID- 27868022
TI  - Magnetic resonance imaging-guided stratified selection of patients for nano
      therapy.

PMID- 27868023
TI  - Ischemia-reperfusion injury: evidences for translational research.

PMID- 27868024
TI  - Cross-talk between cancer-initiating cells and immune cells: considerations for
      combination therapies.

PMID- 27868025
TI  - A sensible approach to targeting STAT3-mediated transcription.

PMID- 27868026
TI  - Preclinical randomized controlled multicenter trials in translational stroke
      research.

PMID- 27868027
TI  - Th2/Th17 reciprocal regulation: twists and turns in the complexity of asthma
      phenotypes.

PMID- 27868028
TI  - Circulating extracellular vesicles containing miRNAs may have utility as early
      biomarkers for cardiac injury.

PMID- 27868029
TI  - Precision medicine with electronic medical records: from the patients and for the
      patients.

PMID- 27868030
TI  - Epidermal growth factor as a prognostic biomarker in chronic kidney diseases.

PMID- 27868031
TI  - Therapeutic illusion: another frontier in Meniere's disease.

PMID- 27868032
TI  - Application of liquid biopsies to identify genomic factors associated with
      therapy resistance in castration resistant prostate cancer.

PMID- 27868034
TI  - Has moderate ischemic mitral regurgitation to be corrected?-Analysis of a
      randomized trial.

PMID- 27868033
TI  - Second line treatment of small cell lung cancer: more is better?

PMID- 27868035
TI  - Did the beneficial renal outcomes with vasopressin VANISH?

PMID- 27868036
TI  - The state of the art in prediction of breast cancer relapse using cell-free
      circulating tumor DNA liquid biopsies.

PMID- 27868037
TI  - The stem cell cocktail: neural reprogramming just got easier.

PMID- 27868038
TI  - As"SIRT"ing the role of an epigenetic modifier in hematopoietic stem cell
      homeostasis.

PMID- 27868039
TI  - Making gametes from pluripotent stem cells: embryonic stem cells or very small
      embryonic-like stem cells?

PMID- 27868040
TI  - Inhibition of MLL1 histone methyltransferase brings the developmental clock back
      to naive pluripotency.
AB  - Embryonic stem cells (ESCs) and the post-implantation epiblast stem cells
      (EpiSCs) portray two different states of pluripotency. They differ with respect
      to epigenetic signatures, dependency of growth factor signaling circuit and cell
      morphology. They are interconvertible, however, with poor reconversion
      efficiency. This is indicative of existence of other unknown regulatory pathways
      govern developmental stage transition. Zhang and colleagues have recently
      demonstrated that pharmacological inhibition of MLL1 histone methyltransferase is
      casually linked to efficient reprogramming of EpiSCs to developmentally competent
      ESCs. MLL1 controlled H3K4me1 serves as an epigenetic valve that ensures
      maintenance of EpiSCs. Removing this barrier leads to global redistribution of
      H3K4me1 at enhancers and target gene promoters, in turn represses EpiSC specific
      genes and reactivates ESC specific transcriptional network. This study
      underscores the critical role of MLL1 in establishing discrete chromatin states
      indispensible for early mammalian developmental events.

PMID- 27868041
TI  - Are we closer to cardiac regeneration?

PMID- 27868042
TI  - Epithelial Dclk1+ cells are not neural crest derived.

PMID- 27868043
TI  - Enterocyte progenitors can dedifferentiate to replace lost Lgr5+ intestinal stem
      cells revealing that many different progenitor populations can regain stemness.

PMID- 27868044
TI  - Stem cells with a view: a look inside a retinal ciliopathy.

PMID- 27868045
TI  - MLL1: the thin red line divides naive and primed pluripotency.

PMID- 27868046
TI  - Stress-induced haematopoietic stem cell proliferation: new roles for p38alpha and
      purine metabolism.

PMID- 27868047
TI  - Personalized models reveal mechanistic and therapeutic insights into CEP290
      associated Leber congenital amaurosis.

PMID- 27868049
TI  - miRNA-324, a potential therapeutic target for paracetamol-induced liver injury.

PMID- 27868048
TI  - Ground state naive pluripotent stem cells and CRISPR/Cas9 gene correction for
      beta-thalassemia.

PMID- 27868050
TI  - RNA editing as an activator of self-renewal in cancer.

PMID- 27868051
TI  - p38alpha-mediated purine metabolism is linked to exit from quiescence of
      hematopoietic stem cells.

PMID- 27868053
TI  - Getting nervous about regeneration.

PMID- 27868052
TI  - Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell
      transplantation for adult T-cell leukemia/lymphoma.
AB  - Adult T-cell leukemia/lymphoma (ATL/ATLL) is a peripheral T-cell neoplasm
      associated with human T-lymphotropic virus type-1 (HTLV-1). Even the currently
      most intensive chemotherapy regimen modified LSG15 (mLSG15, VCAP-AMP-VECP)
      results in a dismal clinical outcome, with a median overall survival of only
      around 1 year. Although allogeneic hematopoietic stem cell transplantation (allo
      HSCT) may lead to long-term remission in a proportion of patients with aggressive
      ATL, the clinical outcome in patients with refractory or relapsed ATL is
      unsatisfactory. The anti-CCR4 antibody mogamulizumab (moga) has been recently
      approved for ATL in Japan, and it is effective in a significant proportion of
      patients with refractory or relapsed ATL. However, there are major concerns about
      the harmful influences of pretransplant moga on the immune reconstitution after
      allo-HSCT. Specifically, moga depletes regulatory T cells (Tregs) for at least a
      few months, which may increase the risk of graft-versus-host disease (GVHD) after
      allo-HSCT. A recent retrospective study from Japan clearly showed that
      pretransplant moga increased the risk of severe and steroid-refractory GVHD,
      which led to increases in non-relapse mortality and overall mortality. To improve
      the overall clinical outcome in patients with relapsed or refractory ATL, more
      studies are needed to incorporate moga without increasing adverse effects on the
      clinical outcome after allo-HSCT. In this review, we aim to provide an updated
      summary of the research related to moga and allo-HSCT.

PMID- 27868054
TI  - Unraveling the mysteries of pre-mRNA splicing in the retina via stem cell
      technology.

PMID- 27868055
TI  - The paradox of Foxd3: how does it function in pluripotency and differentiation of
      embryonic stem cells?
AB  - Uncommitted cells of the early mammalian embryo transition through distinct
      stages of pluripotency, including establishment of ground state "naive"
      pluripotency in the early epiblast, transition to a post-implantation "primed"
      state, and subsequent lineage commitment of the gastrulating epiblast. Previous
      transcriptional profiling of in vitro models to recapitulate early to late
      epiblast transition and differentiation suggest that distinct gene regulatory
      networks are likely to function in each of these states. While the mechanisms
      underlying transition between pluripotent states are poorly understood, the
      forkhead family transcription factor Foxd3 has emerged as a key regulatory
      factor. Foxd3 is required to maintain pluripotent cells of the murine epiblast
      and for survival, self-renewal and pluripotency of embryonic stem cells (ESCs).
      Two recent, simultaneous studies have shed light on how Foxd3 regulates gene
      expression in early cell fate transitions of progenitor cells. While the two
      publications shared some common findings, they also presented some conflicting
      results and suggest different models for the mechanisms underlying Foxd3
      function. Here, we discuss the key similarities and differences between the
      publications, highlight data from the literature relevant to their findings, and
      hypothesize a potential mechanism of Foxd3 action.

PMID- 27868056
TI  - Spotlight on the Schwann cells during the regeneration.

PMID- 27868057
TI  - TGF-beta: a master regulator of the bone marrow failure puzzle in Fanconi anemia.

PMID- 27868058
TI  - GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among
      Phenotypes Using GWAS Results.
AB  - Genome-wide association studies (GWAS) have identified tens of thousands of
      genetic variants associated with hundreds of phenotypes and diseases, which have
      provided clinical and medical benefits to patients with novel biomarkers and
      therapeutic targets. Recently, there has been accumulating evidence suggesting
      that different complex traits share a common risk basis, namely, pleiotropy.
      Previously, a statistical method, namely, GPA (Genetic analysis incorporating
      Pleiotropy and Annotation), was developed to improve identification of risk
      variants and to investigate pleiotropic structure through a joint analysis of
      multiple GWAS datasets. While GPA provides a statistically rigorous framework to
      evaluate pleiotropy between phenotypes, it is still not trivial to investigate
      genetic relationships among a large number of phenotypes using the GPA framework.
      In order to address this challenge, in this paper, we propose a novel approach,
      GPA-MDS, to visualize genetic relationships among phenotypes using the GPA
      algorithm and multidimensional scaling (MDS). This tool will help researchers to
      investigate common etiology among diseases, which can potentially lead to
      development of common treatments across diseases. We evaluate the proposed GPA
      MDS framework using a simulation study and apply it to jointly analyze GWAS
      datasets examining 18 unique phenotypes, which helps reveal the shared genetic
      architecture of these phenotypes.

PMID- 27868059
TI  - Intramyocardial Injection of siRNAs Can Efficiently Establish Myocardial Tissue
      Specific Renalase Knockdown Mouse Model.
AB  - Ischaemia/reperfusion (I/R) injury will cause additional death of cardiomyocytes
      in ischaemic heart disease. Recent studies revealed that renalase was involved in
      the I/R injury. So, the myocardial tissue-specific knockdown mouse models were
      needed for the investigations of renalase. To establish the mouse models,
      intramyocardial injection of siRNAs targeting renalase was performed in mice. The
      wild distribution and high transfection efficiency of the siRNAs were approved.
      And the renalase expression was efficiently suppressed in myocardial tissue.
      Compared with the high cost, time consumption, and genetic compensation risk of
      the Cre/loxP technology, RNA interference (RNAi) technology is much cheaper and
      less time-consuming. Among the RNAi technologies, injection of siRNAs is safer
      than virus. And considering the properties of the I/R injury mouse models, the
      efficiency and durability of injection with siRNAs are acceptable for the
      studies. Altogether, intramyocardial injection of siRNAs targeting renalase is an
      economical, safe, and efficient method to establish myocardial tissue-specific
      renalase knockdown mouse models.

PMID- 27868060
TI  - Selection of Lipases for the Synthesis of Biodiesel from Jatropha Oil and the
      Potential of Microwave Irradiation to Enhance the Reaction Rate.
AB  - The present study deals with the enzymatic synthesis of biodiesel by
      transesterification of Jatropha oil (Jatropha curcas L.) with ethanol in a
      solvent-free system. Seven commercial lipase preparations immobilized by covalent
      attachment on epoxy-polysiloxane-polyvinyl alcohol composite (epoxy-SiO2-PVA)
      were tested as biocatalysts. Among them, immobilized lipases from Pseudomonas
      fluorescens (lipase AK) and Burkholderia cepacia (lipase PS) were the most active
      biocatalysts in biodiesel synthesis, reaching ethyl ester yields (FAEE) of 91.1
      and 98.3% at 72 h of reaction, respectively. The latter biocatalyst exhibited
      similar performance compared to Novozym(r) 435. Purified biodiesel was
      characterized by different techniques. Transesterification reaction carried out
      under microwave irradiation exhibited higher yield and productivity than
      conventional heating. The operational stability of immobilized lipase PS was
      determined in repeated batch runs under conventional and microwave heating
      systems, revealing half-life times of 430.4 h and 23.5 h, respectively.

PMID- 27868061
TI  - Understanding the Pathophysiology of Portosystemic Shunt by Simulation Using an
      Electric Circuit.
AB  - Portosystemic shunt (PSS) without a definable cause is a rare condition, and most
      of the studies on this topic are small series or based on case reports. Moreover,
      no firm agreement has been reached on the definition and classification of
      various forms of PSS, which makes it difficult to compare and analyze the
      management. The blood flow can be seen very similar to an electric current,
      governed by Ohm's law. The simulation of PSS using an electric circuit, combined
      with the interpretation of reported management results, can provide intuitive
      insights into the underlying mechanism of PSS development. In this article, we
      have built a model of PSS using electric circuit symbols and explained clinical
      manifestations as well as the possible mechanisms underlying a PSS formation.

PMID- 27868062
TI  - Apolipoprotein E Gene Variants and Risk of Coronary Heart Disease: A Meta
      Analysis.
AB  - Objectives. Apo E genes involved in lipoprotein synthesis and metabolism are
      considered one of the candidates to CHD. However, the results remain conflicting.
      Methods. We performed this meta-analysis based on 30 published studies including
      11,804 CHD patients and 17,713 controls. Results. Compared with the wild genotype
      E3/3, the variant genotypes ApoEE3/4 and E4/4 were associated with 22% and 45%
      increased risk of CHD, respectively (E3/4 versus E3/3: OR = 1.22, 95% CI = 1.15
      1.29; E4/4 versus E3/3: OR = 1.45, 95% CI = 1.23-1.71). Besides, compared with
      epsilon3 allele, carriers with the epsilon4 allele had a 46% increased risk of
      CHD (OR = 1.46, 95% CI = 1.28-1.66), while the epsilon2 had no significantly
      decreased risk of CHD. In the subgroup analysis by ethnicity, epsilon4 had a 25%
      increased risk of CHD in Caucasians (OR = 1.25, 95% CI = 1.11-1.41), and the
      effects were more evident in Mongolians (OR = 2.29, 95% CI = 1.89-2.77). The
      epsilon2 allele had a decreased risk of CHD in Caucasians (OR = 0.84, 95% CI =
      0.74-0.96), but not in Mongolians. Conclusions. The analysis suggested that
      ApoEepsilon4 mutation was associated with the increased risk of CHD, while
      ApoEepsilon2 allele had a decreased risk of CHD just in Caucasians.

PMID- 27868063
TI  - Changes in the Expression of Biofilm-Associated Surface Proteins in
      Staphylococcus aureus Food-Environmental Isolates Subjected to Sublethal
      Concentrations of Disinfectants.
AB  - Sublethal concentrations (sub-MICs) of certain disinfectants are no longer
      effective in removing biofilms from abiotic surfaces and can even promote the
      formation of biofilms. Bacterial cells can probably adapt to these low
      concentrations of disinfectants and defend themselves by way of biofilm
      formation. In this paper, we report on three Staphylococcus aureus biofilm
      formers (strong B+++, moderate B++, and weak B+) that were cultivated with sub
      MICs of commonly used disinfectants, ethanol or chloramine T, and quantified
      using Syto9 green fluorogenic nucleic acid stain. We demonstrate that 1.25-2.5%
      ethanol and 2500 MUg/mL chloramine T significantly enhanced S. aureus biofilm
      formation. To visualize differences in biofilm compactness between S. aureus
      biofilms in control medium, 1.25% ethanol, or 2500 MUg/mL chloramine T, scanning
      electron microscopy was used. To describe changes in abundance of surface-exposed
      proteins in ethanol- or chloramine T-treated biofilms, surface proteins were
      prepared using a novel trypsin shaving approach and quantified after dimethyl
      labeling by LC-LTQ/Orbitrap MS. Our data show that some proteins with adhesive
      functions and others with cell maintenance functions and virulence factor EsxA
      were significantly upregulated by both treatments. In contrast, immunoglobulin
      binding protein A was significantly downregulated for both disinfectants.
      Significant differences were observed in the effect of the two disinfectants on
      the expression of surface proteins including some adhesins, foldase protein PrsA,
      and two virulence factors.

PMID- 27868064
TI  - Shrimp Protein Hydrolysate Modulates the Timing of Proinflammatory Macrophages in
      Bupivacaine-Injured Skeletal Muscles in Rats.
AB  - This study was designed to determine whether marine-derived proteins other than
      cod could have beneficial effects on inflammation following muscle injury.
      Macrophage and neutrophil densities were measured from bupivacaine-injured
      tibialis anterior muscle of rats fed isoenergetic diets containing either shrimp
      hydrolysate (Shr), casein hydrolysate (CaH), or whole casein (Ca). In this study,
      Shr reduced ED1+-macrophages at day 2 (p = 0.013), day 5 (p = 0.006), and day 14
      after injury (p = 0.038) compared with Ca, indicating faster resolution of
      inflammation in Shr. Except for day 2 after injury where Shr led to lower ED1+
      macrophages compared with CaH (p = 0.006), both Shr and CaH responded similarly
      at days 5, 14, and 28 after injury. This findings suggest that beneficial effects
      of Shr on ED1+-cells might be related to generation of anti-inflammatory peptides
      through the hydrolysis process, in addition to its high content of anti
      inflammatory amino acids. However, while increasing myofiber cross-sectional area
      in noninjured muscles compared with both Ca and CaH, Shr failed to have a
      positive effect in corresponding injured muscles. These data indicate that shrimp
      hydrolysate can facilitate resolution of inflammation after muscle injury mainly
      through modulating proinflammatory macrophage accumulation but have less effect
      on optimal recovery in terms of muscle mass and fiber size.

PMID- 27868065
TI  - Comparative Proteomic Analysis of Light-Induced Mycelial Brown Film Formation in
      Lentinula edodes.
AB  - Light-induced brown film (BF) formation by the vegetative mycelium of Lentinula
      edodes is important for ensuring the quantity and quality of this edible
      mushroom. Nevertheless, the molecular mechanism underlying this phenotype is
      still unclear. In this study, a comparative proteomic analysis of mycelial BF
      formation in L. edodes was performed. Seventy-three protein spots with at least a
      twofold difference in abundance on two-dimensional electrophoresis (2DE) maps
      were observed, and 52 of them were successfully identified by matrix-assisted
      laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI
      TOF/TOF/MS). These proteins were classified into the following functional
      categories: small molecule metabolic processes (39%), response to oxidative
      stress (5%), and organic substance catabolic processes (5%), followed by
      oxidation-reduction processes (3%), single-organism catabolic processes (3%),
      positive regulation of protein complex assembly (3%), and protein metabolic
      processes (3%). Interestingly, four of the proteins that were upregulated in
      response to light exposure were nucleoside diphosphate kinases. To our knowledge,
      this is the first proteomic analysis of the mechanism of BF formation in L.
      edodes. Our data will provide a foundation for future detailed investigations of
      the proteins linked to BF formation.

PMID- 27868066
TI  - Application of Machine Learning Approaches for Classifying Sitting Posture Based
      on Force and Acceleration Sensors.
AB  - Occupational musculoskeletal disorders, particularly chronic low back pain (LBP),
      are ubiquitous due to prolonged static sitting or nonergonomic sitting positions.
      Therefore, the aim of this study was to develop an instrumented chair with force
      and acceleration sensors to determine the accuracy of automatically identifying
      the user's sitting position by applying five different machine learning methods
      (Support Vector Machines, Multinomial Regression, Boosting, Neural Networks, and
      Random Forest). Forty-one subjects were requested to sit four times in seven
      different prescribed sitting positions (total 1148 samples). Sixteen force sensor
      values and the backrest angle were used as the explanatory variables (features)
      for the classification. The different classification methods were compared by
      means of a Leave-One-Out cross-validation approach. The best performance was
      achieved using the Random Forest classification algorithm, producing a mean
      classification accuracy of 90.9% for subjects with which the algorithm was not
      familiar. The classification accuracy varied between 81% and 98% for the seven
      different sitting positions. The present study showed the possibility of
      accurately classifying different sitting positions by means of the introduced
      instrumented office chair combined with machine learning analyses. The use of
      such novel approaches for the accurate assessment of chair usage could offer
      insights into the relationships between sitting position, sitting behaviour, and
      the occurrence of musculoskeletal disorders.

PMID- 27868067
TI  - Purification and Characterization of a Thermostable beta-Mannanase from Bacillus
      subtilis BE-91: Potential Application in Inflammatory Diseases.
AB  - beta-mannanase has shown compelling biological functions because of its
      regulatory roles in metabolism, inflammation, and oxidation. This study separated
      and purified the beta-mannanase from Bacillus subtilis BE-91, which is a powerful
      hemicellulose-degrading bacterium using a "two-step" method comprising
      ultrafiltration and gel chromatography. The purified beta-mannanase (about 28.2
      kDa) showed high specific activity (79, 859.2 IU/mg). The optimum temperature and
      pH were 65 degrees C and 6.0, respectively. Moreover, the enzyme was highly
      stable at temperatures up to 70 degrees C and pH 4.5-7.0. The beta-mannanase
      activity was significantly enhanced in the presence of Mn2+, Cu2+, Zn2+, Ca2+,
      Mg2+, and Al3+ and strongly inhibited by Ba2+ and Pb2+. Km and Vmax values for
      locust bean gum were 7.14 mg/mL and 107.5 MUmol/min/mL versus 1.749 mg/mL and
      33.45 umol/min/mL for Konjac glucomannan, respectively. Therefore, beta-mannanase
      purified by this work shows stability at high temperatures and in weakly acidic
      or neutral environments. Based on such data, the beta-mannanase will have
      potential applications as a dietary supplement in treatment of inflammatory
      processes.

PMID- 27868068
TI  - Cone Beam X-Ray Luminescence Tomography Imaging Based on KA-FEM Method for Small
      Animals.
AB  - Cone beam X-ray luminescence tomography can realize fast X-ray luminescence
      tomography imaging with relatively low scanning time compared with narrow beam X
      ray luminescence tomography. However, cone beam X-ray luminescence tomography
      suffers from an ill-posed reconstruction problem. First, the feasibility of
      experiments with different penetration and multispectra in small animal has been
      tested using nanophosphor material. Then, the hybrid reconstruction algorithm
      with KA-FEM method has been applied in cone beam X-ray luminescence tomography
      for small animals to overcome the ill-posed reconstruction problem, whose
      advantage and property have been demonstrated in fluorescence tomography imaging.
      The in vivo mouse experiment proved the feasibility of the proposed method.

PMID- 27868069
TI  - Early Inflammatory Response following Traumatic Brain Injury in Rabbits Using
      USPIO- and Gd-Enhanced MRI.
AB  - Purpose. To monitor the inflammatory response (IR) following traumatic brain
      injury (TBI) before and after the rehabilitation of the blood-brain barrier (BBB)
      in rabbits using USPIO- and Gd-enhanced MRI. Materials and Methods. Twenty white
      big-eared rabbits with mild TBI (mTBI) were randomly and equally divided into
      four groups. Rabbits were sacrificed for the brain specimens immediately after
      the last MRI-monitoring. Sequences were tse-T1WI, tse-T2WI, Gd-T1WI, and USPIO
      T1WI. Dynamical MRI presentations were evaluated and compared with pathological
      findings for each group. Results. Twenty-four hours after injury, all rabbits
      displayed high signal foci on T2WI, while only 55% lesions could be found on Gd
      T1WI and none on USPIO-T1WI. The lesions were enhanced on Gd-T1WI in 100%
      subjects after 48 h and the enhancement sizes augmented to the largest after 72
      h. At the time point of 72 h after TBI, 90% lesions were enhanced by USPIO. Five
      days after injury, 19 lesions showed decreased Gd-enhancement and one
      disappeared; however, USPIO-enhancement became larger than before. Pathological
      findings showed microglias slightly appeared in dense leukocytes at 48 h, but
      became the dominant inflammatory cells after five days. Conclusions. Dynamic IR
      following injury could be monitored by combination of Gd- and USPIO-MRI in mTBI
      rabbits.

PMID- 27868070
TI  - Adaptation and Feasibility Study of a Digital Health Program to Prevent Diabetes
      among Low-Income Patients: Results from a Partnership between a Digital Health
      Company and an Academic Research Team.
AB  - Background. The feasibility of digital health programs to prevent and manage
      diabetes in low-income patients has not been adequately explored. Methods.
      Researchers collaborated with a digital health company to adapt a diabetes
      prevention program for low-income prediabetes patients at a large safety net
      clinic. We conducted focus groups to assess patient perspectives, revised lessons
      for improved readability and cultural relevance to low-income and Hispanic
      patients, conducted a feasibility study of the adapted program in English and
      Spanish speaking cohorts, and implemented real-time adaptations to the program
      for commercial use and for a larger trial of in multiple safety net clinics.
      Results. The majority of focus group participants were receptive to the program.
      We modified the curriculum to a 5th-grade reading level and adapted content based
      on patient feedback. In the feasibility study, 54% of eligible contacted patients
      expressed interest in enrolling (n = 23). Although some participants' computer
      access and literacy made registration challenging, they were highly satisfied and
      engaged (80% logged in at least once/week). Conclusions. Underserved prediabetic
      patients displayed high engagement and satisfaction with a digital diabetes
      prevention program despite lower digital literacy skills. The collaboration
      between researchers and a digital health company enabled iterative improvements
      in technology implementation to address challenges in low-income populations.

PMID- 27868071
TI  - Mean Daily Dosage of Aspirin and the Risk of Incident Alzheimer's Dementia in
      Patients with Type 2 Diabetes Mellitus: A Nationwide Retrospective Cohort Study
      in Taiwan.
AB  - Background. Type 2 diabetes mellitus patients are known to have higher risk of
      developing dementia while aspirin use has been shown to prevent incident
      dementia. This study was conducted to evaluate the potential benefits of aspirin
      use on dementia in patients with type 2 diabetes mellitus and identify the
      appropriate dosage of aspirin that provides the most benefit. Method. A Taiwan
      nationwide, population-based retrospective 8-year study was employed to analyze
      the association between the use of aspirin and incidence of dementia including
      Alzheimer's disease and non-Alzheimer's dementia using multivariate Cox
      proportional hazards regression model and adjusting for several potential
      confounders. Results. Regular aspirin use in mean daily dosage of within 40 mg
      was associated with a decreased risk of developing incident Alzheimer's dementia
      in patients with type 2 diabetes mellitus (adjusted HR of 0.51 with 95% CI of
      0.27-0.97, p value 0.041). Conclusion. A mean daily dosage of aspirin use within
      40 mg might decrease the risk of developing Alzheimer's disease in patients with
      type 2 diabetes mellitus.

PMID- 27868073
TI  - The Crosstalk between Myeloid Derived Suppressor Cells and Immune Cells: To
      Establish Immune Tolerance in Transplantation.
AB  - Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of
      myeloid precursor and progenitor cells and endowed with a robust
      immunosuppressive activity in multiple pathophysiological conditions. Recent
      studies have uncovered the crosstalk between MDSCs and immune cells (i.e.,
      natural killer cells, dendritic cells, macrophages, natural killer T cells, and
      regulatory T cells) and its role in the establishment and maintenance of immune
      tolerant microenvironment in transplantation. Considering their strong
      immunosuppressive capability, MDSCs could become a prospective clinical regimen
      during transplantation tolerance induction, resulting in long-term graft survival
      with decreased or without immunosuppressive drugs. The review summarized recent
      research advances in this field and looked ahead at the research directions in
      the future.

PMID- 27868072
TI  - The Role of TLR4 on B Cell Activation and Anti-beta2GPI Antibody Production in
      the Antiphospholipid Syndrome.
AB  - High titer of anti-beta2-glycoprotein I antibodies (anti-beta2GPI Ab) plays a
      pathogenic role in antiphospholipid syndrome (APS). Numerous studies have focused
      on the pathological mechanism in APS; however, little attention is paid to the
      immune mechanism of production of anti-beta2GPI antibodies in APS. Our previous
      study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the
      maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized
      with human beta2-glycoprotein I (beta2GPI). TLR4 is required for the activation
      of B cells and the production of autoantibody in mice treated with beta2GPI.
      However, TLR4 provides a third signal for B cell activation and then promotes B
      cells better receiving signals from both B cell antigen receptor (BCR) and CD40,
      thus promoting B cell activation, surface molecules expression, anti-beta2GPI Ab
      production, and cytokines secretion and making B cell functioning like an antigen
      presenting cell (APC). At the same time, TLR4 also promotes B cells producing
      antibodies by upregulating the expression of B-cell activating factor (BAFF). In
      this paper, we aim to review the functions of TLR4 in B cell immune response and
      antibody production in autoimmune disease APS and try to find a new way for the
      prevention and treatment of APS.

PMID- 27868075
TI  - Novel Mutation of Interferon-gamma Receptor 1 Gene Presenting as Early Life
      Mycobacterial Bronchial Disease.
AB  - Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of
      inherited disorders characterized by localized or disseminated infections caused
      by atypical mycobacteria. Interferon-gamma receptor 1 (IFNGR1) deficiency was the
      first identified genetic disorder recognized as MSMD. Mutations in the genes
      encoding IFNGR1 can be recessive or dominant and cause complete or partial
      receptor deficiency. We present the case of a 21/2-year-old boy with a history of
      recurrent wheezing, diagnosed with endobronchial mycobacterial infection.
      Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene,
      a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This
      case demonstrates that (a) Interferon-gamma receptor deficiency can present
      resembling common disorders of the lung; (b) mycobacterial infections should be
      suspected when parenchymal lung disease, hilar lymphadenopathy, and endobronchial
      disease are present; and (c) high index of suspicion for immunodeficiency should
      be maintained in patients with disseminated nontubercular mycobacterial
      infection.

PMID- 27868074
TI  - CD63 Promotes Hemocyte-Mediated Phagocytosis in the Clam, Paphia undulata.
AB  - As one of the surface membrane proteins of tetraspanin family, CD63 plays a
      crucial role in cellular trafficking and endocytosis, which also is associated
      with activation of a wide variety of immune cells. Here, the homolog of CD63 was
      characterized from one marine mollusk, Paphia undulata, which is designated as Pu
      CD63. The complete cDNA of Pu-CD63 is 1,738 bp in length with an open reading
      frame (ORF) of 849 bp, encoding a 282 amino acid protein with four putative
      hydrophobic transmembrane helixes. Bioinformatic analysis revealed that Pu-CD63
      contains one putative YXXO consensus motif of "110-YVII-113" and one N
      glycosylation site "155-NGT-157" within the large extracellular loop (LEL)
      region, supporting its conserved function in plasma membrane and
      endosomal/lysosomal trafficking. Moreover, temporal expression profile analysis
      demonstrates a drastic induction in the expression of CD63 in hemocytes after
      pathogenic challenge with either V. parahaemolyticus or V. alginolyticus. By
      performing dsRNA-mediate RNAi knockdowns of CD63, a dramatic reduction in
      hemocytes phagocytic activity to pathogenic Vibrio is recorded by flow cytometry,
      revealing the definite role of Pu-CD63 in promoting hemocyte-mediated
      phagocytosis. Therefore, our work has greatly enhanced our understanding about
      primitive character of innate immunity in marine mollusk.

PMID- 27868076
TI  - Synovial C-Shaped Tibial Footprint of the Anterior Cruciate Ligament.
AB  - BACKGROUND: Although numerous anatomic studies about the anterior cruciate
      ligament (ACL) structure and attachments have been performed, these studies have
      not reached consensus on the ACL footprint. PURPOSE: To investigate the existing
      controversy regarding the morphology of the tibial ACL insertion (footprint) and
      confirm histologically that the tibial ACL footprint is not completely filled
      with ligament tissue. STUDY DESIGN: Descriptive laboratory study. METHODS: The
      tibial ACL footprint was dissected from 20 different fresh-frozen cadaveric knees
      (all males; mean age, 68.8 +/- 5.4 years [range, 55-80 years]; mean weight, 78 +/
      6.6 kg [range, 45-93 kg]). Two knees, 1 with severe osteoarthritis and 1 with
      previous knee surgery, were excluded. The tibial ACL insertion was observed, and
      this area was longitudinally divided into 4 parallel slices (0%-25%, 25-50%, 50%
      75%, and 75%-100%), embedded in paraffin wax, and stained with hematoxylin-eosin,
      alcian blue, and picrosirius-polarization. The specimens were measured using a
      microscope to determine the distances from the anterior to the posterior border
      of the ACL ligament tibial insertion and the distance from the posterior border
      to the end of the ligament fibers of the ACL ligament tibial insertions. RESULTS:
      The 18 evaluated knee specimens confirmed the finding of a C-shaped tibial
      insertion of the ACL. The measurements showed that the ligament (vertical
      parallel collagen fibers) occupied only 30.8% of the complete insertion. The
      remaining area was filled with synovial tissue, demonstrating histologically the
      "C" shape. CONCLUSION: This study confirms macroscopically the C-shaped tibial
      insertion of the ACL and shows histologically that synovial tissue is an indirect
      insertion filling the major part of the footprint. CLINICAL RELEVANCE: This
      anatomic study suggests a different shape of the ACL tibial footprint, which may
      be useful for new perspectives regarding ACL reconstruction surgery research.

PMID- 27868078
TI  - The Role of Technology in the Neonatal Screening Laboratory.

PMID- 27868077
TI  - Platelet-Rich Plasma Injections With Needle Tenotomy for Gluteus Medius
      Tendinopathy: A Registry Study With Prospective Follow-up.
AB  - BACKGROUND: Gluteal tendinopathy is a prevalent condition that can be associated
      with significant pain and disability. To date, no studies have prospectively
      assessed the efficacy of intratendinous platelet-rich plasma (PRP) injections as
      a minimally invasive treatment for gluteus medius tendinopathy. PURPOSE: To
      prospectively assess the efficacy of intratendinous PRP injections as treatment
      for chronic recalcitrant gluteus medius tendinopathy. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: During the study period between July 2011 and
      November 2015, data were collected from the Hospital for Special Surgery Center
      for Hip Preservation Outcomes Registry on participants who underwent ultrasound
      guided intratendinous PRP injections for recalcitrant gluteus medius tendinosis
      and/or partial tears of the tendon associated with moderate to severe lateral hip
      pain for longer than 3 months. All participants were assessed pre- and
      postinjection with 4 outcome measures: modified Harris Hip Score (mHHS), Hip
      Outcome Score-Activities of Daily Living subscale (HOS-ADL), Hip Outcome Score
      Sport-Specific subscale (HOS-Sport), and the International Hip Outcome Tool-33
      (iHOT-33). Demographic data, including age, sex, height, weight, body mass index,
      and smoking status, were also collected. RESULTS: A total of 21 patients were
      included in the study, with a mean follow-up of 19.7 months (range, 12.1-32.3
      months). The mean improvements from preinjection to postinjection follow-up were
      56.73 to 74.17 for mHHS, 68.93 to 84.14 for HOS-ADL, 45.54 to 66.72 for HOS
      Sport, and 34.06 to 66.33 for iHOT-33. All mean outcome measure improvements were
      clinically and statistically significant (P < .001). Length of follow-up was
      positively correlated with improvements in HOS-ADL (P = .021) and HOS-Sport (P =
      .004) scores. No adverse events were observed during or after the procedure.
      CONCLUSION: In this registry study with prospective follow-up, we found
      ultrasound-guided intratendinous PRP injections to be a safe and effective
      treatment option for chronic recalcitrant gluteus medius tendinopathy due to
      moderate to severe tendinosis and/or partial tendon tears. Well-powered
      randomized controlled studies are warranted to confirm our findings and further
      define the ideal candidates for this treatment.

PMID- 27868079
TI  - Semantic prediction in language comprehension: evidence from brain potentials.
AB  - Do people predict specific word-forms during language comprehension? In an Event
      Related Potential (ERP) study participants read German sentences with predictable
      (The goalkeeper claims that the slick ball was easy to CATCH.) and unpredictable
      (The kids boasted that the young horse was easy to SADDLE.) verbs. Verbs were
      either consistent with the expected word-form (catch/saddle) or inconsistent and
      therefore led to ungrammaticality (*catches/*saddles). ERPs within the N400 time
      window were modulated by predictability but not by the surface-form of the verbs,
      suggesting that no exact word-forms were predicted. Based on our results we will
      argue that predictions included semantic rather than form-information.
      Furthermore, ungrammatical verbs led to a strong P600, probably due to task
      saliency whereas correct unpredictable verbs elicited an anterior post-N400
      positivity. Because the contexts were moderately constraining, this might reflect
      discourse revision processes rather than inhibition of a predicted word.

PMID- 27868080
TI  - Risk, Activism, and Empowerment: Women's Breast Cancer in Venezuela.
AB  - The prevalence of breast cancer in Venezuela is particularly alarming, which is
      attributed to healthcare inequalities, low health literacy, and lagging
      compliance with prevention methods (i.e., screening and mammography). While the
      right to health is acknowledged by the Venezuelan constitution, activism beyond
      governmental confines is required to increase women's breast cancer awareness and
      decrease mortality rates. Through the development of social support and strategic
      communicative methods enacted by healthcare providers, it may be possible to
      empower women with the tools necessary for breast cancer prevention. This paper
      discusses issues surrounding women's breast cancer, such as awareness of the
      disease and its risks, self-advocacy, and the roles of activists, healthcare
      providers, and society. Specifically, it describes a four-year action-oriented
      research project developed in Venezuela, which was a collaborative work among
      researchers, practitioners, NGOs, patients, journalists, and policymakers. The
      outcomes include higher levels of awareness and interest among community members
      and organizations to learn and seek more information about women's breast cancer,
      better understandings of the communicated messages, more media coverage and
      medical consultations, increasing positive patient treatments, expansion of
      networking of NGOs, as well as a widely supported declaration for a national
      response against breast cancer in Venezuela.

PMID- 27868082
TI  - Knowledge, Attitudes, and Practices of Parents Facing Child and Adolescent
      Obesity in Brazzaville, Congo.
AB  - The study aimed to assess obesity-related knowledge, attitudes, and practices of
      parents when facing child and adolescent obesity in order to improve the quality
      of care. A case-control study was conducted from February 1 to July 1, 2013. The
      study compared parents of obese school children (group 1 or cases; n = 254) and
      those school children without obesity (group 2 or controls; n = 254). These
      children were drawn from public and private primary schools of Brazzaville
      (Congo). Obesity-related knowledge was satisfactory in 83.5% of the cases,
      attitudes were correct in 29% of the cases, and the practices good in 25.6% of
      the cases. The parents' obesity-related knowledge was satisfactory when the
      socioeconomic level of the family was high (P < .02), the mothers' educational
      level greater than primary (P < .001), and the fathers' educational level was
      greater than primary (P < 10-4). The same observation was obtained with obesity
      related attitudes and practices of the parents when correct. This influence
      remained after the adaptation of fathers' educational level. In conclusion, the
      disease-related knowledge of parents can be considered satisfactory in the
      majority of the cases; however, obesity-related attitudes and practices remain
      incorrect in most of the cases.

PMID- 27868081
TI  - Blood-brain barrier integrity, intrathecal immunoactivation, and neuronal injury
      in HIV.
AB  - OBJECTIVE: Although blood-brain barrier (BBB) impairment has been reported in HIV
      infected individuals, characterization of this impairment has not been clearly
      defined. METHODS: BBB integrity was measured by CSF/plasma albumin ratio in this
      cross-sectional study of 631 HIV-infected individuals and 71 controls. We also
      analyzed CSF and blood HIV RNA and neopterin, CSF leukocyte count, and
      neurofilament light chain protein (NFL) concentrations. The HIV-infected
      participants included untreated neuroasymptomatic patients, patients with
      untreated HIV-associated dementia (HAD), and participants on suppressive
      antiretroviral treatment (ART). RESULTS: The albumin ratio was significantly
      increased in patients with HAD compared to all other groups. There were no
      significant differences between untreated neuroasymptomatic participants, treated
      participants, and controls. BBB integrity, however, correlated significantly with
      CSF leukocyte count, CSF HIV RNA, serum and CSF neopterin, and age in untreated
      neuroasymptomatic participants. In a multiple linear regression analysis, age,
      CSF neopterin, and CSF leukocyte count stood out as independent predictors of
      albumin ratio. A significant correlation was found between albumin ratio and CSF
      NFL in untreated neuroasymptomatic patients and in participants on ART. Albumin
      ratio, age, and CD4 cell count were confirmed as independent predictors of CSF
      NFL in multivariable analysis. CONCLUSIONS: BBB disruption was mainly found in
      patients with HAD, where BBB damage correlated with CNS immunoactivation. Albumin
      ratios also correlated with CSF inflammatory markers and NFL in untreated
      neuroasymptomatic participants. These findings give support to the association
      among BBB deterioration, intrathecal immunoactivation, and neuronal injury in
      untreated neuroasymptomatic HIV-infected individuals.

PMID- 27868083
TI  - Combining social cognitive treatment, cognitive remediation, and functional
      skills training in schizophrenia: a randomized controlled trial.
AB  - This study examined the efficacy of an integrative cognitive remediation program
      (REHACOP) in improving cognition and functional outcome in patients with
      schizophrenia. The program combines cognitive remediation, social cognitive
      intervention, and functional skills training. Few studies have attempted this
      approach. One hundred and eleven patients diagnosed with schizophrenia were
      randomly assigned to either the cognitive remediation group (REHACOP) or an
      active control group (occupational activities) for 4 months (three sessions per
      week, 90 min). Primary outcomes were change on general neurocognitive performance
      and social cognition, including theory of mind (ToM), emotion perception (EP),
      attributional style, and social perception (SP). Secondary outcomes included
      changes on clinical symptoms (Positive and Negative Syndrome Scale) and
      functional outcome (UCSD Performance-Based Skills Assessment and the Global
      Assessment of Functioning). The trial was registered with clinicaltrials.gov
      (NCT02796417). No baseline group differences were found. Significant differences
      were found in the mean change between the REHACOP group and control group in
      neurocognition ([Formula: see text]), SP ([Formula: see text]), ToM ([Formula:
      see text]), EP ([Formula: see text]), negative symptoms ([Formula: see text]),
      emotional distress ([Formula: see text]), Global Assessment of Functioning
      ([Formula: see text]), and UCSD Performance-Based Skills Assessment ([Formula:
      see text]). The combination of cognitive remediation, social cognitive
      intervention, and functional skills training demonstrated statistically
      significant and clinically meaningful changes in neurocognition, social
      cognition, negative, and functional disability.

PMID- 27868084
TI  - The association between bone turnover markers and kyphosis in community-dwelling
      older adults.
AB  - PURPOSE: Hyperkyphosis, accentuated curvature of the thoracic spine, is often
      attributed to osteoporosis, yet its underlying pathophysiology is not well
      understood. Bone turnover markers (BTM) reflect the dynamic process of bone
      formation and resorption. This study examined the association between serum BTM
      levels and kyphosis in community-dwelling older adults. METHODS: Between 2003 and
      2006, 760 men and women in the Rancho Bernardo Study age 60 and older had blood
      drawn and kyphosis measured. Fasting serum was assayed for N-telopeptide (NTX)
      and procollagen type 1 n-terminal propeptide (P1NP), markers of bone resorption
      and formation, respectively. Participants requiring two or more 1.7 cm blocks
      under their head to achieve a neutral supine position were classified as having
      accentuated kyphosis. Analyses were stratified by sex and use of estrogen therapy
      (ET). Odds of accentuated kyphosis were calculated for each standard deviation
      increase in log-transformed BTM. RESULTS: Mean age was 75 years. Overall, 51% of
      341 non-ET using women, 41% of 111 ET-using women, and 75% of 308 men had
      accentuated kyphosis. In adjusted models, higher P1NP and NTX were associated
      with decreased odds of accentuated kyphosis in non-ET using women (P1NP: OR =
      0.78 [95% CI, 0.58-0.92]; NTX: OR = 0.68 [95% CI, 0.54-0.86]), but not in men or
      ET-using women (p > 0.05). CONCLUSIONS: The selective association of higher bone
      turnover with reduced odds of accentuated kyphosis in non-ET using women suggests
      that elevated BTM were associated with a lower likelihood of hyperkyphosis only
      in the low estrogen/high BTM environment characteristic of postmenopausal women
      who are not using ET.

PMID- 27868086
TI  - Links between mRNA splicing, mRNA quality control, and intellectual disability.
AB  - In recent years, the impairment of RNA binding proteins that play key roles in
      the post-transcriptional regulation of gene expression has been linked to
      numerous neurological diseases. These RNA binding proteins perform critical mRNA
      processing steps in the nucleus, including splicing, polyadenylation, and export.
      In many cases, these RNA binding proteins are ubiquitously expressed raising key
      questions about why only brain function is impaired. Recently, mutations in the
      ZC3H14 gene, encoding an evolutionarily conserved, polyadenosine RNA binding
      protein, have been linked to a nonsyndromic form of autosomal recessive
      intellectual disability. Thus far, research on ZC3H14 and its Nab2 orthologs in
      budding yeast and Drosophila reveals that ZC3H14/Nab2 is important for mRNA
      processing and neuronal patterning. Two recent studies now provide evidence that
      ZC3H14/Nab2 may function in the quality control of mRNA splicing and export and
      could help to explain the molecular defects that cause neuronal dysfunction and
      lead to an inherited form of intellectual disability. These studies on
      ZC3H14/Nab2 reveal new clues to the puzzle of why loss of the ubiquitously
      expressed ZC3H14 protein specifically affects neurons.

PMID- 27868085
TI  - Child Trauma Exposure and Psychopathology: Mechanisms of Risk and Resilience.
AB  - Exposure to trauma in childhood is associated with elevated risk for multiple
      forms of psychopathology. Here we present a biopsychosocial model outlining the
      mechanisms that link child trauma with psychopathology and protective factors
      that can mitigate these risk pathways. We focus on four mechanisms of enhanced
      threat processing: information processing biases that facilitate rapid
      identification of environmental threats, disruptions in learning mechanisms
      underlying the acquisition of fear, heightened emotional responses to potential
      threats, and difficulty disengaging from negative emotional content. Supportive
      relationships with caregivers, heightened sensitivity to rewarding and positive
      stimuli, and mature amygdala-prefrontal circuitry each serve as potential buffers
      of these risk pathways, highlighting novel directions for interventions aimed at
      preventing the onset of psychopathology following child trauma.

PMID- 27868087
TI  - Diabetic Wound Healing and Activation of Nrf2 by Herbal Medicine.
AB  - Nrf2 defense is a very important cellular mechanism to control oxidative stress,
      which is implicated in wound healing. Nrf2 can induce many cytoprotective genes,
      including HO-1, NQO1 and G6PD. Among many natural products that have been
      reported as Nrf2 activators, sulforaphane and curcumin have been studied more
      widely than any others, and both are in clinical trials for non-cancerous
      disorders. Recently, we reported 4-ethyl catechol and 4-vinyl catechol as Nrf2 co
      factors that can induce Nrf2 as potently as sulforaphane and curcumin. These new
      Nrf2 co-factors were identified in hot aqueous extract of an herbal medicine
      Barleria lupulina, and fermented Noni (Morinda citrifolia) juice, which are used
      traditionally for diabetic wound healing.

PMID- 27868088
TI  - Five Decades of Remarkable but Slowing Change in U.S. Women's Economic and Social
      Status and Political Participation.
AB  - The last fifty years of women's social and economic progress have been lauded as
      the "grand gender convergence," the "second demographic transition," and the
      "rise of women"-terms pointing to the remarkable transformation in women's social
      and economic roles since the 1960s. Many metrics document these changes.

PMID- 27868090
TI  - Extraction and Analysis of Terpenes/Terpenoids.
AB  - Terpenes/terpenoids constitute one of the largest classes of natural products,
      this is due to the incredible chemical diversity that can arise from the
      biochemical transformations of the relatively simple prenyl diphosphate starter
      units. All terpenes/terpenoids comprise a hydrocarbon backbone that is generated
      from the various length prenyl diphosphates (a polymer chain of prenyl units).
      Upon ionization (removal) of the diphosphate group, the remaining allylic
      carbocation intermediates can be coaxed down complex chemical cascades leading to
      diverse linear and cyclized hydrocarbon backbones, which can then be further
      modified with a wide range of functional groups (e.g. alcohol, ketones, etc.) and
      substituent additions (e.g. sugars, fatty acids). Because of this chemical
      diversity, terpenes/terpenoids have great industrial uses as flavors, fragrances,
      high grade lubricants, biofuels, agricultural chemicals and medicines. The
      protocols presented here focus on the extraction of terpenes/terpenoids from
      various plant sources and have been divided into extraction methods for
      terpenes/terpenoids with various levels of chemical decoration, from the relative
      small, nonpolar, volatile hydrocarbons to substantially large molecules with
      greater physical complexity due to their chemical modifications.

PMID- 27868089
TI  - Adaptive Evolution of Phosphorus Metabolism in Prochlorococcus.
AB  - Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high
      light-adapted ecotype HLI of the marine picocyanobacterium Prochlorococcus
      marinus thrives. Physiological and regulatory control of phosphorus acquisition
      and partitioning has been observed in HLI both in culture and in the field;
      however, the optimization of phosphorus metabolism and associated gains for its
      phosphorus-limited-growth (PLG) phenotype have not been studied. Here, we
      reconstructed a genome-scale metabolic network of the HLI axenic strain MED4
      (iJC568), consisting of 568 metabolic genes in relation to 794 reactions
      involving 680 metabolites distributed in 6 subcellular locations. iJC568 was used
      to quantify metabolic fluxes under PLG conditions, and we observed a close
      correspondence between experimental and computed fluxes. We found that MED4 has
      minimized its dependence on intracellular phosphate, not only through drastic
      depletion of phosphorus-containing biomass components but also through network
      wide reductions in phosphate-reaction participation and the loss of a key enzyme,
      succinate dehydrogenase. These alterations occur despite the stringency of having
      relatively few pathway redundancies and an extremely high proportion of essential
      metabolic genes (47%; defined as the percentage of lethal in silico gene
      knockouts). These strategies are examples of nutrient-controlled adaptive
      evolution and confer a dramatic growth rate advantage to MED4 in phosphorus
      limited regions. IMPORTANCE Microbes are known to employ three basic strategies
      to compete for limiting elemental resources: (i) cell quotas may be adjusted by
      alterations to cell physiology or by substitution of a more plentiful resource,
      (ii) stressed cells may synthesize high-affinity transporters, and (iii) cells
      may access more costly sources from internal stores, by degradation, or by
      petitioning other microbes. In the case of phosphorus, a limiting resource in
      vast oceanic regions, the cosmopolitan cyanobacterium Prochlorococcus marinus
      thrives by adopting all three strategies and a fourth, previously unknown
      strategy. By generating a detailed model of its metabolism, we found that strain
      MED4 has evolved a way to reduce its dependence on phosphate by minimizing the
      number of enzymes involved in phosphate transformations, despite the stringency
      of nearly half of its metabolic genes being essential for survival. Relieving
      phosphorus limitation, both physiologically and throughout intermediate
      metabolism, substantially improves phosphorus-specific growth rates.

PMID- 27868092
TI  - Endourologic Diagnosis and Robotic Treatment of a Giant Fibroepithelial Polyp of
      the Ureter.
AB  - Background: Fibroepithelial polyps (FEPs) are a rare cause of ureteropelvic
      junction (UPJ) obstruction. Radiologists and urologists are not always confident
      with this disease because of its rarity, complex diagnosis, and heterogeneity of
      the available treatment options. Case Presentation: We present the endourologic
      diagnosis and the robotic management of a ureteral polyp close to the left UPJ. A
      16-year-old woman with a 12 years history of left lumbar pain was referred to our
      Center. A computed tomography scan detected a left hydronephrosis with no signs
      of obstructions at MAG-3 scintigraphy. The endourologic evaluation revealed a
      giant FEP of the left ureter, which was removed surgically with a
      videolaparoscopic robot-assisted approach. Conclusion: Considering that
      conventional radiologic imaging techniques can hardly detect a ureteral FEP, an
      endourologic study of the urinary tract is mandatory to directly observe the
      polyp. The mini-invasive treatment of ureteral FEPs is feasible and safe, and
      should be considered as first option in young patients.

PMID- 27868091
TI  - Aftermath of Grade 3 Ureteral Injury from Passage of a Ureteral Access Sheath:
      Disaster or Deliverance?
AB  - Background: The ureteral access sheath (UAS) has revolutionized the management of
      urinary pathology in the upper tract by providing rapid repeatable access to the
      upper urinary tract. However, in many practices, it remains a controversial tool
      in endourology given concerns of possible ureteral injury and presumed long-term
      sequela from those injuries. This case suggests that these concerns may be more
      hypothetical than real. Case Presentation: A 32-year-old female with a history of
      recurrent nephrolithiasis presented with left-sided symptomatic renal colic. She
      was found to have bilateral nephrolithiasis plus a left 6 * 5 mm proximal
      ureteral stone with associated moderate hydroureteronephrosis. The patient failed
      a trial of passage and as such was taken to the operating room for an elective
      ureteroscopy (URS) during which she sustained a Grade 3 ureteral splitting
      injury, measuring ~2-3 cm, to the distal ureter from passage of the 16F UAS. At
      the end of the procedure a 7/10F endopyelotomy stent was placed. On follow-up URS
      at 6 weeks, there was no visual evidence of ureteral injury. A Lasix renal scan
      obtained 8 weeks after stent removal showed no evidence of obstruction.
      Conclusion: High-grade ureteral injuries sustained from UAS passage are rare.
      However, when injuries of this nature occur, the concern over long-term damage to
      the ureter may well be overstated.

PMID- 27868093
TI  - Conservative Management of Combined Pleural and Splenic Injury During
      Percutaneous Nephrostolithotomy.
AB  - Splenic injuries related to percutaneous nephrostolithotomy (PCNL) are
      infrequent. Herein, we report a combined splenic and pleural injury incurred
      during PCNL along with radiographic images documenting the complication. A review
      of management techniques for similar injuries is included.

PMID- 27868094
TI  - Heart of Darkness.
AB  - Significant literature has an impact on the reader. Reading the novella Heart of
      Darkness by Joseph Conrad as a young boy rose emotions comparable to those I felt
      when losing a patient after percutaneous nephrolithotomy (PCNL) as a grown up.
      The case of a 37-year-old woman with bilateral staghorn and a fatal outcome after
      PCNL is presented and alternatives are discussed.

PMID- 27868095
TI  - Unsuspected Malignancy During Percutaneous Nephrolithotomy: The Snake in the
      Grass.
AB  - Squamous cell carcinoma of the upper tract (SCC-UT) is a rare neoplasm that
      disproportionately affects patients with longstanding nephrolithiasis. Diagnosis
      is challenging and typically comes at late stages; as such, the prognosis is
      poor. The absence of a reliable diagnostic predictor for SCC highlights the need
      to keep the diagnosis in mind for at-risk patient populations. In this study, we
      describe a small case series of rapidly progressive SCC-UT incidentally
      discovered during percutaneous nephrolithotomy.

PMID- 27868096
TI  - Novel Use of Folate-Targeted Intraoperative Fluorescence, OTL38, in Robot
      Assisted Laparoscopic Partial Nephrectomy: Report of the First Three Cases.
AB  - Partial nephrectomy is now the preferred surgical option for small renal tumors
      because it allows nephron preservation without compromising oncologic clearance.
      Its outcomes depend on the surgeon's ability to continuously identify the edges
      of the tumor during resection, thus leaving an adequate margin around the tumor
      without excessive removal of normal parenchyma, as well as keeping a short
      ischemic time. Folate receptors are highly abundant in the normal kidney, and
      there is a difference in folate receptor expression between malignant and normal
      renal tissues. Thus, the use of fluorescent agents that target folate receptors
      should result in differential fluorescence between the tumor and surrounding
      parenchyma during partial nephrectomy, which, in turn, helps tumor demarcation
      for identification and resection. A phase 2 study on the novel use of OTL38 in
      robot-assisted laparoscopic partial nephrectomy is currently in progress in our
      institution. The outcomes of the first three cases have shown the possible
      advantages of OTL38 in intraoperative tumor identification before resection and
      recognition of residual disease in the surrounding parenchyma after resection.
      The tumors typically appeared dark while the surrounding parenchyma showed
      brighter fluorescence. Immediately after tumor resection, the margins of all the
      specimens appeared to have a uniformly bright fluorescence, suggestive of an
      intact margin of normal renal parenchyma along the plane of excision. The pattern
      of intraoperative fluorescence correlates well with immunohistochemistry. No
      OTL38-related adverse effects have been seen among these three patients. We
      present the outcomes of these three cases, illustrated with intraoperative and
      immunohistochemistry images.

PMID- 27868097
TI  - Percutaneous Nephrolithotomy in Rare Bleeding Disorders: A Case Report and Review
      of the Literature.
AB  - Surgery in patients with congenital or acquired coagulation defects has always
      been challenging and requires special care with a multidisciplinary approach.
      Percutaneous nephrolithotomy (PCNL) is a standard procedure performed in patients
      with kidney stones. Although prone to bleeding more than most of the widely
      performed surgical procedures, there are not much data regarding PCNL in patients
      with bleeding disorders or coagulation defects. There are only case reports or
      series with a small number of patients for the patients with common coagulation
      defects, including hemophilias. Moreover, there are no reports about PCNL in rare
      bleeding disorders. In this study, we reported a case referred for kidney stone
      treatment and diagnosed as Factor VII deficiency during preoperative evaluation.
      Because it is one of the rare bleeding disorders, we also reviewed the literature
      in this field.

PMID- 27868099
TI  - Endourologic and Open Ureterolithotomy and Common Sheath Reimplant for Large
      Bladder and Distal Ureteral Calculi.
AB  - A twenty-eight-year-old female with a history of suprapubic pain and recurrent
      urinary tract infections presents for urology referral with a kidney, ureter, and
      bladder radiograph showing a 4.4 cm bladder calculus and 6.5 cm distal left
      ureteral stone. She underwent effective cystolitholapaxy of the bladder stone.
      Endourologic attempt (left ureteroscopy) was unsuccessful because of ureteral
      stone burden. Findings at ureteroscopy revealed a duplicated system on the left
      with the lower pole moiety joining just proximal to the ureteral orifice. The
      stone was found to be in the upper pole moiety ureter. An open ureterolithotomy
      was performed with intraoperative ureteroscopic laser lithotripsy and common
      sheath ureteral reimplant. Furthermore, a previously placed stent was found to be
      encrusted at the time of the ureterolithotomy. Effective ureteroscopy and
      lasering were performed through the ureterotomy up to the renal pelvis of the
      upper pole ureter.

PMID- 27868098
TI  - Neuroendocrine Tumor of the Ureter: A Zebra Among Horses.
AB  - Primary neuroendocrine tumors of the upper urinary tract are extremely rare. We
      report a case of de novo small cell carcinoma of the ureter that presented
      masquerading as a distal ureteral stone. A 55-year-old lady presented to our
      clinic with 1 month history of right lower back pain and hematuria. Her history
      was notable for stage 1B mixed clear cell-endometroid cancer of the uterus status
      post radical abdominal hysterectomy with adjuvant radiotherapy, 7 years before
      the current episode. The patient had no evidence of recurrence. Initial
      noncontrast imaging suggested a 2.5 mm calculus in the distal right ureter and
      hydronephrosis; however, ureteroscopy revealed a large fleshy mass at the
      location. Histopathologic evaluation demonstrated the lesion to be primary small
      cell carcinoma of the ureter, without evidence of it being a derivative of the
      prior gynecologic malignancy. Metastatic work-up revealed high burden
      retroperitoneal adenopathy. The patient was started on Cisplatin-based
      neoadjuvant chemotherapy with plan for nephroureterectomy in the future. At 3
      months follow-up, the patient was doing well with significant shrinkage of
      retroperitoneal adenopathy and no evidence of disease progression.

PMID- 27868100
TI  - Nephropleural Fistula Effectively Managed with Serial Thoracentesis: A Case
      Report.
AB  - Nephropleural fistulae are rare but serious thoracic complications of
      percutaneous nephrolithotomy (PCNL). Herein, we present the management of a 54
      year-old female with a delayed presentation of nephropleural fistula. The role of
      serial thoracentesis as a safe, less invasive, less painful alternative to tube
      thoracostomy is highlighted. In select cases, this may represent an attractive
      management strategy for nephropleural fistula after PCNL.

PMID- 27868101
TI  - Simultaneous Retroperitoneal Robotic Partial Nephrectomy and Hepatectomy for
      Synchronous Renal-Cell Carcinoma and Hepatocellular Carcinoma in a Cirrhotic
      Patient.
AB  - Background: The development of laparoscopic and robotic surgeries represents the
      modern era with the objective of improving patient outcomes; this surgical method
      is widespread in urology and general surgery. Retroperitoneal
      laparoscopic/robotic surgery is common in urologic surgery, but not in liver
      surgery. Tumors located in the posterosuperior aspect of the liver are difficult
      to access using a transperitoneal approach, and control of bleeding can also be
      difficult, especially in patients with cirrhosis. Case Presentation: Herein, we
      present a 66-year-old man who had a cirrhotic liver with concurrent renal and
      hepatic tumors. The renal tumor was located at the upper pole of the right kidney
      and the liver tumor was located at the liver dome (segment VII); the patient
      underwent simultaneous robotic hepatectomy and partial nephrectomy with a
      retroperitoneal approach. Conclusion: To our knowledge, this is the first case
      involving a retroperitoneal approach for a simultaneous robotic hepatectomy and
      partial nephrectomy; this method was feasible and safe. We hope this approach
      serves as an alternative surgical method for patients with synchronous renal and
      posterior segment liver tumors.

PMID- 27868102
TI  - Case Report of Percutaneous Tract Seeding of Renal Pelvic Tumor: 8-Year Journey.
AB  - A 58-year-old female presented with renal colic and was found to have renal
      transitional cell carcinoma at the time of percutaneous surgery. She developed
      percutaneous tract seeding that clinically presented as subcutaneous skin
      nodules. After local treatment with surgical excision and radiation treatment,
      the patient developed retroperitoneal recurrence 5 years later. Percutaneous
      tract seeding is rare. There is no general consensus on prevention of tract
      seeding during percutaneous resection of renal urothelial tumors. Various
      recommendations from the literature are discussed.

PMID- 27868103
TI  - Integrative representations and analyses of vaccine-induced intended protective
      immunity and unintended adverse events using ontology-based and theory-guided
      approaches.

PMID- 27868105
TI  - Feasibility of automated 3-dimensional magnetic resonance imaging pancreas
      segmentation.
AB  - PURPOSE: With the advent of MR guided radiotherapy, internal organ motion can be
      imaged simultaneously during treatment. In this study, we evaluate the
      feasibility of pancreas MRI segmentation using state-of-the-art segmentation
      methods. METHODS AND MATERIAL: T2 weighted HASTE and T1 weighted VIBE images were
      acquired on 3 patients and 2 healthy volunteers for a total of 12 imaging
      volumes. A novel dictionary learning (DL) method was used to segment the pancreas
      and compared to t mean-shift merging (MSM), distance regularized level set
      (DRLS), graph cuts (GC) and the segmentation results were compared to manual
      contours using Dice's index (DI), Hausdorff distance and shift of the-center-of
      the-organ (SHIFT). RESULTS: All VIBE images were successfully segmented by at
      least one of the auto-segmentation method with DI >0.83 and SHIFT <=2 mm using
      the best automated segmentation method. The automated segmentation error of HASTE
      images was significantly greater. DL is statistically superior to the other
      methods in Dice's overlapping index. For the Hausdorff distance and SHIFT
      measurement, DRLS and DL performed slightly superior to the GC method, and
      substantially superior to MSM. DL required least human supervision and was faster
      to compute. CONCLUSION: Our study demonstrated potential feasibility of automated
      segmentation of the pancreas on MRI images with minimal human supervision at the
      beginning of imaging acquisition. The achieved accuracy is promising for organ
      localization.

PMID- 27868106
TI  - Neutrophils as Possible Therapeutic Targets in Severe Influenza Pneumonia.

PMID- 27868104
TI  - Adaptive Stress Responses During Tumor Metastasis and Dormancy.
AB  - To survive inhospitable environments, tumor cells are forced to remodel their
      signaling pathways by altering transcription, translation, and post-translational
      modifications. This adaptation is regulated in a spatial and temporal manner and
      gives rise to individual tumor cells with distinct gene expression and metabolic
      signatures. Such phenotypic heterogeneity is the result of tumor cell plasticity,
      which-together with the genetic background of the tumor-determines whether cells
      resist environmental stress, enter dormancy, or metastasize. This review
      summarizes our understanding of how tumor cells exploit the cellular stress
      response to balance proliferation, differentiation, and survival signals, and to
      remodel local and distant environments. We focus in particular on tumor
      metastasis, which is the greatest impediment to clinical management of cancers
      today.

PMID- 27868107
TI  - Class I HLA haplotypes form two schools that educate NK cells in different ways.
AB  - Natural killer (NK) cells are lymphocytes having vital functions in innate and
      adaptive immunity, as well as placental reproduction. Controlling education and
      functional activity of human NK cells are various receptors that recognize HLA
      class I on the surface of tissue cells. Epitopes of polymorphic HLA-A,-B and -C
      are recognized by equally diverse killer cell immunoglobulin-like receptors
      (KIR). In addition, a peptide cleaved from the leader sequence of HLA-A,-B or -C
      must bind to HLA-E for it to become a ligand for the conserved CD94:NKG2A
      receptor. Methionine/threonine dimorphism at position -21 of the leader sequence
      divides HLA-B allotypes into a majority having -21T that do not supply HLA-E
      binding peptides and a minority having -21M, that do. Genetic analysis of human
      populations worldwide shows how haplotypes with -21M HLA-B rarely encode the KIR
      ligands: Bw4+HLA-B and C2+HLA-C KIR. Thus there are two fundamental forms of HLA
      haplotype: one preferentially supplying CD94:NKG2A ligands, the other
      preferentially supplying KIR ligands. -21 HLA-B dimorphism divides the human
      population into three groups: M/M, M/T and T/T. Mass cytometry and assays of
      immune function, shows how M/M and M/T individuals have CD94:NKG2A+ NK cells
      which are better educated, phenotypically more diverse and functionally more
      potent than those in T/T individuals. Fundamental new insights are given to
      genetic control of NK cell immunity and the evolution that has limited the number
      of NK cell receptor ligands encoded by an HLA haplotype. These finding suggest
      new ways to dissect the numerous clinical associations with HLA class I.

PMID- 27868108
TI  - Inflammatory monocytes hinder antiviral B cell responses.
AB  - Antibodies are critical for protection against viral infections. However, several
      viruses, such as lymphocytic choriomeningitis virus (LCMV), avoid the induction
      of early protective antibody responses by poorly understood mechanisms. Here we
      analyzed the spatiotemporal dynamics of B cell activation to show that, upon
      subcutaneous infection, LCMV-specific B cells readily relocate to the
      interfollicular and T cell areas of the draining lymph node where they
      extensively interact with CD11b+Ly6Chi inflammatory monocytes. These myeloid
      cells were recruited to lymph nodes draining LCMV infection sites in a type I
      interferon-, CCR2-dependent fashion and they suppressed antiviral B cell
      responses by virtue of their ability to produce nitric oxide. Depletion of
      inflammatory monocytes, inhibition of their lymph node recruitment or impairment
      of their nitric oxide-producing ability enhanced LCMV-specific B cell survival
      and led to robust neutralizing antibody production. In conclusion, our results
      identify inflammatory monocytes as critical gatekeepers that prevent antiviral B
      cell responses and suggest that certain viruses take advantage of these cells to
      prolong their persistence within the host.

PMID- 27868110
TI  - A GENERIC PACKAGING TECHNIQUE USING FLUIDIC ISOLATION FOR LOW-DRIFT IMPLANTABLE
      PRESSURE SENSORS.
AB  - This paper reports on a generic packaging method for reducing drift in
      implantable pressure sensors. The described technique uses fluidic isolation by
      encasing the pressure sensor in a liquid-filled medical-grade polyurethane
      balloon; thus, isolating it from surrounding aqueous environment that is the
      major source of baseline drift. In-vitro tests using commercial micromachined
      piezoresistive pressure sensors show an average baseline drift of 0.006 cmH2O/day
      (0.13 mmHg/month) for over 100 days of saline soak test, as compared to 0.101
      cmH2O/day (2.23 mmHg/month) for a non-fluidic-isolated one soaked for 18 days. To
      our knowledge, this is the lowest reported drift for an implantable pressure
      sensor.

PMID- 27868111
TI  - Preparation and sensing properties of a nitrogen-rich ferrocene-imidazole
      quinoxaline triad decorated with pyrrole rings.
AB  - The synthesis and sensing properties of the nitrogen-rich ferrocene-imidazole
      quinoxaline triad 1 decorated with two pyrrole rings have been described. Due to
      its ditopic nature, this molecule behaves as an ion-pair receptor for Ni2+cations
      and AcO- anions, although no affinity for either of the discrete ions is
      observed. It also displays the rare property consistent with the cooperative AND
      recognition of ion pairs. Thus, this receptor shows an important enhancement for
      binding AcO- anions when it is co-bound to Hg2+cations, whereas no affinity for
      the free receptor by the anion is observed.

PMID- 27868109
TI  - Air Pollution and Lung Function Loss: The Importance of Metabolic Syndrome.

PMID- 27868112
TI  - UPLC-MS/MS investigation of beta-glucan oligosaccharide oxidation.
AB  - Polysaccharide degradation mediated by hydroxyl radicals (HO) or lytic
      monooxygenases (LPMOs) is relevant in various biological and industrial
      processes. Thereby, the Fenton-induced (H2O2/Fe2+) oxidation of mixed-linkage (1
      >3,1->4)-beta-d-glucan (BG), a cereal dietary fibre with several well-established
      health promoting properties, shows potential for modulating BG functionality. The
      precise identification of oxidation products, however, is impeded by their
      diversity due to the indiscriminate nature of HO, the large molecular weight, and
      the corresponding low frequency of discrete alterations along the polymer chain.
      In this paper, we studied the Fenton-induced degradation of several
      constitutionally isomeric glucotetraoses as BG model compounds by hydrophilic
      interaction UPLC-MS/MS in negative ion, high resolution mode. The influence of
      the beta-(1->3)-linkage on the reaction was investigated with regard to
      degradation kinetics, formation of products, and MS/MS fragmentation patterns.
      The position and occurrence of a beta-(1->3)-bond had no influence on the
      degradation kinetics. Classification into primary and secondary acidic oxidation
      products by monitoring their progress over time is also demonstrated, implying
      complexation of primary aldonic acid products by the catalytic iron and
      subsequently facilitated site-specific secondary oxidation, underlining the
      metal's importance beyond its role as HO-generating catalyst. Similarly to
      oxidations mediated by certain LPMOs, thorough MS/MS-analysis of selected
      products and comparison with synthesised standards confirmed two types of
      glycosidic cleavage cascades induced by HO-mediated H-atom abstraction at C1 and
      C3/C4, producing gluconic acids, native oligosaccharides, and oxo-oligomers
      (carbonyl at non-reducing end). Additionally, systematic study of other oxo
      products from the different isomers and rationalisation of MS/MS fragmentation
      mechanisms allowed for the identification of potentially diagnostic fragment
      signals for oxidised cereal BG.

PMID- 27868113
TI  - Magnetic and transport properties of Fe4 single-molecule magnets: a theoretical
      insight.
AB  - Here, methods of density functional theory (DFT) were employed to study the
      magnetic and transport properties of a star-shaped single-molecule magnet Fe4S =
      5 complex deposited on a gold surface. The study devoted to the magnetic
      properties focused on changes in the exchange coupling constants and magnetic
      anisotropy (zero-field splitting parameters) of the isolated and deposited
      molecules. Molecule-surface interactions induced significant changes in the
      antiferromagnetic exchange coupling constants because these depend closely on the
      geometry of the metal complex. Meanwhile, the magnetic anisotropy remained almost
      constant. Transport properties were analysed using two different approaches.
      First, we studied the change in magnetic anisotropy by reducing and oxidizing the
      Fe4 complex as in a Coulomb blockade mechanism. Then we studied the coherent
      tunnelling using DFT methods combined with Green functions. Spin filter behaviour
      was found because of the different numbers of alpha and beta electrons, due to
      the S = 5 ground state.

PMID- 27868114
TI  - Knot theory in modern chemistry.
AB  - Knot theory is a branch of pure mathematics, but it is increasingly being applied
      in a variety of sciences. Knots appear in chemistry, not only in synthetic
      molecular design, but also in an array of materials and media, including some not
      traditionally associated with knots. Mathematics and chemistry can now be used
      synergistically to identify, characterise and create knots, as well as to
      understand and predict their physical properties. This tutorial review provides a
      brief introduction to the mathematics of knots and related topological concepts
      in the context of the chemical sciences. We then survey the broad range of
      applications of the theory to contemporary research in the field.

PMID- 27868115
TI  - A novel coordination polymer based on Co(ii) hexanuclear clusters with azide and
      carboxylate bridges: structure, magnetism and its application as a Li-ion battery
      anode.
AB  - A novel Co(ii) coordination polymer, [Co(H2O)6][Co6(bpybdc)2(N3)10(H2O)4].8H2O
      (bpybdc2- = 1,1'-bis(3,5-dicarboxylatophenyl)-4,4'-bipyridinium), has been
      synthesized from a rigid zwitterionic tetracarboxylate ligand and azide. In this
      compound, hexacobalt clusters with mixed MU-1,1-azide, MU3-1,1,1-azide and MU-1,3
      carboxylate bridges are linked into chains by MU-1,3-azide bridges, and the
      chains are interlinked into 2-fold interpenetrated three-dimensional frameworks
      through the organic ligand and hydrogen bonds mediated by hexaaquacobalt(ii)
      complex ions. Magnetic analysis suggested that intracluster ferromagnetic and
      intercluster antiferromagnetic interactions work together to give overall
      antiferromagnetic ground states for the azide and carboxylate bridged chain. When
      applied as an anode for lithium-ion batteries, the coordination polymer changes
      into an amorphous phase and exhibits a relatively high reversible capacity of 510
      mA h g-1 with stable cycling behavior and rate performance.

PMID- 27868117
TI  - Heteroleptic mononuclear compounds of ruthenium(ii): synthesis, structural
      analyses, in vitro antitumor activity and in vivo toxicity on zebrafish embryos.
AB  - The limitations of platinum complexes in cancer treatment have motivated the
      extensive investigation into other metal complexes such as ruthenium. We herein
      present the synthesis and characterization of a new family of ruthenium compounds
      1a-5a with the general formula [Ru(bipy)2L][CF3SO3]2 (bipy = 2,2'-bipyridine; L =
      bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental
      analysis, ES-MS, 1H and 31P-{1H} NMR, FTIR and conductivity measurements. The
      molecular structures of four Ru(ii) complexes were determined by single crystal X
      ray diffraction. All compounds displayed moderate cytotoxic activity in vitro
      against human A2780 ovarian, MCF7 breast and HCT116 colorectal tumor cells.
      Compound 5a was the most cytotoxic compound against A2780 and MCF7 tumor cells
      with an IC50 of 4.75 +/- 2.82 MUM and 20.02 +/- 1.46 MUM, respectively. The
      compounds showed no cytotoxic effect on normal human primary fibroblasts but
      rather considerable selectivity for A2780, MCF7 and HCT116 tumor cells. All
      compounds induce apoptosis and autophagy in A2780 ovarian carcinoma cells and
      some nuclear DNA fragmentation. All compounds interact with CT-DNA with intrinsic
      binding constants in the order 1a > 4a > 2a > 3a > 5a. The observed hyperchromic
      effect may be due to the electrostatic interaction between positively charged
      cations and the negatively charged phosphate backbone at the periphery of the
      double helix-CT-DNA. Interestingly, compound 1a shows a concentration dependent
      DNA double strand cleavage. In addition in vivo toxicity has been evaluated on
      zebrafish embryos unveiling the differential toxicity between the compounds, with
      LC50 ranging from 8.67 mg L-1 for compound 1a to 170.30 mg L-1 for compound 2a.

PMID- 27868119
TI  - Synthetic routes to iron chalcogenide nanoparticles and thin films.
AB  - Iron chalcogenides are earth abundant, cheap and environmentally benign materials
      that have seen extensive research directed toward a range of applications, most
      notably for photovoltaics. The most common forms of materials for these
      applications are either nanoparticles or thin films. This perspective seeks to
      summarise the key synthetic routes to these materials by highlighting the key
      aspects that lead to control over phase and morphology.

PMID- 27868121
TI  - Explosive enantiospecific decomposition of aspartic acid on Cu surfaces.
AB  - Aspartic acid adsorbed on Cu surfaces is doubly deprotonated. On chiral
      Cu(643)R&S its enantiomers undergo enantiospecific decomposition via an
      autocatalytic explosion. Once initiated, the decomposition mechanism proceeds via
      sequential cleavage of the C3-C4 and C1-C2 bonds each yielding CO2, followed by
      conversion of the remaining species into N[triple bond, length as m-dash]CCH3.

PMID- 27868118
TI  - Varying structural motifs in the salen based metal complexes of Co(ii), Ni(ii)
      and Cu(ii): synthesis, crystal structures, molecular dynamics and biological
      activities.
AB  - Herein, we report the structural and biological activities of a deprotonated
      Schiff base ligand (H2L) {H2L = 1,1'-(1E,1'E)-(2,4,6-trimethyl-1,3
      phenylene)bis(azan-1-yl-1-ylidene)bis(methan-1-yl-1-ylidene)dinaphthalen-2-ol}
      towards Co(ii), Ni(ii) and Cu(ii) complexes obtained under different conditions.
      Four new metal complexes have been synthesized: isostructural dimers [Co(L)]2
      (1)/[Cu(L)]2 (3), a monomer (Cl3NiH2L).(Et3NH) (2) and a tetramer [Cu(L)]4 (4).
      The bioactivity of 1-3 has been investigated through molecular docking with DNA
      and various proteins, known to be involved in the proliferation of viral diseases
      or progression of cancer. Complex 1 shows the best results, through a strong
      binding affinity with NS2B/NS3 protease (dengue virus) in terms of binding energy
      (-11.21 kcal mol-1) and inhibition constant (6.02 nM). The experimental evidence
      for the effective binding of 1-4 with the Bovine Serum Albumin (BSA) protein and
      calf thymus DNA (CT-DNA) is in agreement with our molecular docking results. In
      addition, the cytotoxicity and antibacterial activity of 1-4 were examined and
      found to be compatible with biological systems, with 4 showing the highest
      antibacterial activity. All four complexes were analyzed by elemental analysis
      and UV/vis analysis, and their molecular structures were authenticated by single
      crystal X-ray studies.

PMID- 27868122
TI  - Fine tuning through valence bond tautomerization of ancillary ligands in
      ruthenium(ii) arene complexes for better anticancer activity and enzyme
      inhibition properties.
AB  - Four new ruthenium arene PTA type complexes have been synthesized using
      substituted picolinamide derivatives as ancillary ligands and characterized by
      spectroscopic methods. In one of the complexes, the ancillary ligand has shown an
      unprecedented valence-bond tautomerization in the presence of an ammonium salt to
      act as a polar neutral donor ligand making the ligand more prone towards
      substitution. The same compound has shown remarkable antiproliferative activity
      against three cancer cell lines with GI50 values comparable to Adriamycin, a
      known therapeutic drug. Along with this it also strongly inhibits the action of
      thioredoxin reductase, which might be a probable reason for the enhanced
      proliferative action of the valence-bond tautomerized compound.

PMID- 27868125
TI  - Coumestrol modulates Akt and Wnt/beta-catenin signaling during the attenuation of
      adipogenesis.
AB  - Coumestrol is a natural phytochemical present in plants such as red clover and
      soy, and has been reported to stimulate the estrogen receptor as a major
      phytoestrogen. While the molecular mechanisms responsible for the anti-adipogenic
      effects of phytoestrogens such as genistein and daidzein have been previously
      investigated, the effects of coumestrol on adipogenesis remain to be elucidated.
      We observed that coumestrol dose-dependently attenuates MDI (mixture of 3
      isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced lipid
      accumulation, consistent with an earlier study, while significantly inhibiting
      MDI-induced adipogenesis in the first 48 hours of differentiation, a critical
      time window for anti-adipogenic effects. Coumestrol treatment suppressed MDI
      induced protein expression of PPARgamma and C/EBPalpha in adipocytes, leading to
      the subsequent downregulation of FAS and aP2 expression. Akt and GSK3beta were
      phosphorylated shortly after MDI stimulation, and these responses were inhibited
      by coumestrol treatment. Coumestrol also increased LRP6 protein expression,
      resulting in the recovery of beta-catenin downregulation by MDI, while
      attenuating MDI-induced downregulation of Wnt10b. In addition, mRNA and protein
      expression of c-Myc and cyclin D1, target genes of beta-catenin, were both
      recovered by coumestrol treatment. These results suggest that coumestrol inhibits
      adipocyte differentiation via regulation of Akt and Wnt/beta-catenin signaling
      and may have potential for development as an agent to prevent adipogenesis.

PMID- 27868126
TI  - New insights into mammalian signaling pathways using microfluidic pulsatile
      inputs and mathematical modeling.
AB  - Temporally modulated input mimics physiology. This chemical communication
      strategy filters the biochemical noise through entrainment and phase-locking.
      Under laboratory conditions, it also expands the observability space for
      downstream responses. A combined approach involving microfluidic pulsatile
      stimulation and mathematical modeling has led to deciphering of hidden/unknown
      temporal motifs in several mammalian signaling pathways and has provided
      mechanistic insights, including how these motifs combine to form distinct band
      pass filters and govern fate regulation under dynamic microenvironment. This
      approach can be utilized to understand signaling circuit architectures and to
      gain mechanistic insights for several other signaling systems. Potential
      applications include synthetic biology and biotechnology, in developing
      pharmaceutical interventions, and in developing lab-on-chip models.

PMID- 27868128
TI  - The role of STIM1 in the Cr(vi)-induced [Ca2+]i increase and cell injury in L-02
      hepatocytes.
AB  - Hexavalent chromium [Cr(vi)] is a potent cytotoxin and carcinogen. In recent
      years, drinking water contamination with Cr(vi) has become a worldwide problem of
      significant public health importance, thus much attention has been paid to the
      investigation of Cr(vi)-induced hepatotoxicity. The concentration of
      intracellular calcium ions ([Ca2+]i) was found to be increased after Cr(vi)
      exposure, but the exact underlying mechanisms involved in the Ca2+ homeostasis
      imbalance remain poorly characterized. In the present study, by utilizing the
      antagonist of store-operated calcium channels (SOCCs) 2-aminoethoxydiphenyl
      borate (2-APB), small interfering RNA against stromal interaction molecule 1 (si
      STIM1) and antioxidant N-acetylcysteine (NAC), we found that Cr(vi) induces
      [Ca2+]i increase, cell viability loss and transaminase (AST/ALT) leakage, and
      that these could be suppressed by both 2-APB and si-STIM1. NAC significantly
      alleviated Cr(vi)-induced up-regulation of STIM1, phosphorylated-extracellular
      signal-regulated kinases 1 and 2 (p-ERK1/2), ERK1/2 and nuclear factor kappaB (NF
      kappaB). By utilizing the ERK inhibitor U0126 and the NF-kappaB inhibitor
      pyrrolidine dithiocarbamate (PDTC), we confirmed that STIM1 can be regulated by
      ERK and NF-kappaB. Thus we concluded that STIM1 plays a role in the Cr(vi)
      induced [Ca2+]i increase and cell injury. Our current data provide new insights
      into the mechanisms of STIM1 function in Cr(vi)-induced hepatotoxicity, and may
      provide experimental clues for the prevention and treatment of liver diseases in
      the occupational population exposed to Cr(vi).

PMID- 27868127
TI  - Digital DNA detection based on a compact optofluidic laser with ultra-low sample
      consumption.
AB  - DNA lasers self-amplify optical signals from a DNA analyte as well as
      thermodynamic differences between sequences, allowing quasi-digital DNA
      detection. However, these systems have drawbacks, such as relatively large sample
      consumption and complicated dye labelling. Moreover, although the lasing signal
      can detect the target DNA, it is superimposed on an unintended fluorescence
      background, which persists for non-target DNA samples as well. From an optical
      point of view, it is thus not truly digital detection and requires spectral
      analysis to identify the target. In this work, we propose and demonstrate an
      optofluidic laser that has a single layer of DNA molecules as the gain material.
      A target DNA produces intensive laser emission comparable to existing DNA lasers,
      while any unnecessary fluorescence background is successfully suppressed. As a
      result, the target DNA can be detected with a single laser pulse, in a truly
      digital manner. Since the DNA molecules cover only a single layer on the surface
      of the laser microcavity, the DNA sample consumption is a few orders of magnitude
      lower than that of existing DNA lasers. Furthermore, the DNA molecules are
      stained by simply immersing the microcavity in the intercalating dye solution,
      and thus the proposed DNA laser is free of any complex dye-labelling process
      prior to analysis.

PMID- 27868129
TI  - Identifying differential networks based on multi-platform gene expression data.
AB  - Exploring how the structure of a gene regulatory network differs between two
      different disease states is fundamental for understanding the biological
      mechanisms behind disease development and progression. Recently, with rapid
      advances in microarray technologies, gene expression profiles of the same
      patients can be collected from multiple microarray platforms. However, previous
      differential network analysis methods were usually developed based on a single
      type of platform, which could not utilize the common information shared across
      different platforms. In this study, we introduce a multi-view differential
      network analysis model to infer the differential network between two different
      patient groups based on gene expression profiles collected from multiple
      platforms. Unlike previous differential network analysis models that need to
      analyze each platform separately, our model can draw support from multiple data
      platforms to jointly estimate the differential networks and produce more accurate
      and reliable results. Our simulation studies demonstrate that our method
      consistently outperforms other available differential network analysis methods.
      We also applied our method to identify network rewiring associated with platinum
      resistance using TCGA ovarian cancer samples. The experimental results
      demonstrate that the hub genes in our identified differential networks on the
      PI3K/AKT/mTOR pathway play an important role in drug resistance.

PMID- 27868131
TI  - Methods Open - A New Journal Track Starting in 2017.
AB  - From 2017 (volume 56) onwards the journal Methods of Information in Medicine will
      consist of two tracks. Authors can decide to submit their manuscript to either
      the subscription track that continues to publish its six print and electronic
      (non-open access) issues for journal subscribers, or the new Methods Open track
      that will consist of digitally published manuscripts (as gold open access). These
      two tracks will constitute from 2017 on the journal's Tandem Model.
      Simultaneously, Methods will introduce a double-blinded review process and
      reviewer assessment by the submitting authors. Implications of these changes for
      both authors and reviewers are discussed. With these steps, Methods aims to
      improve the visibility of the journal and contribute to sharing research results
      as timely and as widely as possible and thereby to promote scientific progress.

PMID- 27868132
TI  - Exploring Possibilities for Transforming Established Subscription-based
      Scientific Journals into Open Access Journals. Present Situation, Transformation
      Criteria, and Exemplary Implementation within Trans-O-MIM.
AB  - BACKGROUND: Based on today's information and communication technologies the open
      access paradigm has become an important approach for adequately communicating new
      scientific knowledge. OBJECTIVES: Summarizing the present situation for journal
      transformation. Presenting criteria for adequate transformation as well as a
      specific approach for it. Describing our exemplary implementation of such a
      journal transformation. METHODS: Studying the respective literature as well as
      discussing this topic in various discussion groups and meetings (primarily of
      editors and publishers, but also of authors and readers), with long term
      experience as editors and /or publishers of scientific publications as
      prerequisite. RESULTS: There is a clear will, particularly of political and
      funding organizations, towards open access publishing. In spite of this, there is
      still a large amount of scientific knowledge, being communicated through
      subscription-based journals. For successfully transforming such journals into
      open access, sixteen criteria for a goal-oriented, stepwise, sustainable, and
      fair transformation are suggested. The Tandem Model as transformation approach is
      introduced. Our exemplary implementation is done in the Trans-O-MIM project. It
      is exploring strategies, models and evaluation metrics for journal
      transformation. As instance the journal Methods of Information in Medicine will
      apply the Tandem Model from 2017 onwards. CONCLUSIONS: Within Trans-O-MIM we will
      reach at least nine of the sixteen criteria for adequate transformation. It was
      positive to implement Trans-O-MIM as international research project. After first
      steps for transforming Methods have successfully been made, challenges will
      remain, among others, in identifying appropriate incentives for open access
      publishing in order to support its transformation.

PMID- 27868133
TI  - Ensemble Pruning for Glaucoma Detection in an Unbalanced Data Set.
AB  - BACKGROUND: Random forests are successful classifier ensemble methods consisting
      of typically 100 to 1000 classification trees. Ensemble pruning techniques reduce
      the computational cost, especially the memory demand, of random forests by
      reducing the number of trees without relevant loss of performance or even with
      increased performance of the sub-ensemble. The application to the problem of an
      early detection of glaucoma, a severe eye disease with low prevalence, based on
      topographical measurements of the eye background faces specific challenges.
      OBJECTIVES: We examine the performance of ensemble pruning strategies for
      glaucoma detection in an unbalanced data situation. METHODS: The data set
      consists of 102 topographical features of the eye background of 254 healthy
      controls and 55 glaucoma patients. We compare the area under the receiver
      operating characteristic curve (AUC), and the Brier score on the total data set,
      in the majority class, and in the minority class of pruned random forest
      ensembles obtained with strategies based on the prediction accuracy of greedily
      grown sub-ensembles, the uncertainty weighted accuracy, and the similarity
      between single trees. To validate the findings and to examine the influence of
      the prevalence of glaucoma in the data set, we additionally perform a simulation
      study with lower prevalences of glaucoma. RESULTS: In glaucoma classification all
      three pruning strategies lead to improved AUC and smaller Brier scores on the
      total data set with sub-ensembles as small as 30 to 80 trees compared to the
      classification results obtained with the full ensemble consisting of 1000 trees.
      In the simulation study, we were able to show that the prevalence of glaucoma is
      a critical factor and lower prevalence decreases the performance of our pruning
      strategies. CONCLUSIONS: The memory demand for glaucoma classification in an
      unbalanced data situation based on random forests could effectively be reduced by
      the application of pruning strategies without loss of performance in a population
      with increased risk of glaucoma.

PMID- 27868134
TI  - Developing and validating a localised, self-training mindfulness programme for
      older Singaporean adults: effects on cognitive functioning and implications for
      healthcare.
AB  - There is a paucity of research available on the effect of mindfulness on
      cognitive function. However, the topic has recently gained more attention due to
      the ageing population in Singapore, catalysed by recent findings on brain
      function and cellular ageing. Recognising the potential benefits of practising
      mindfulness, we aimed to develop a localised, self-training mindfulness
      programme, guided by expert practitioners and usability testing, for older
      Singaporean adults. This was followed by a pilot study to examine the potential
      cognitive benefits and feasibility of this self-training programme for the
      cognitive function of older adults in Singapore. We found that the results from
      the pilot study were suggestive but inconclusive, and thus, merit further
      investigation.

PMID- 27868137
TI  - Assessing Acute Itch Intensity: General Labelled Magnitude Scale is More Reliable
      than Classic Visual Analogue Scale.

PMID- 27868135
TI  - A review of bioresorbable scaffolds: hype or hope?
AB  - In the field of percutaneous coronary intervention, the evolution of coronary
      metal stents has been well established for the past three decades, but research
      on bioresorbable scaffolds has only gained momentum in the recent past. Although
      second-generation drug-eluting metal stents are the gold standard for the
      treatment of obstructive coronary artery disease, a few drawbacks exist. The
      development of bioresorbable scaffolds is an attempt to overcome the limitations
      of metal stents. This review highlights the rationale for the bioresorbable
      scaffold, its properties and potential applications. It also focuses on the
      current evidence and concerns regarding the application of the bioresorbable
      scaffold in day-to-day practice.

PMID- 27868136
TI  - Increased Activity and Apoptosis of Eosinophils in Blister Fluids, Skin and
      Peripheral Blood of Patients with Bullous Pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering skin disease that is more
      common in elderly individuals. The aim of this study was to determine the
      functional activity of eosinophils in patients with BP compared with healthy
      donors. Blood, skin and blister-derived eosinophils were strongly activated in
      patients with BP, seen by increased surface expression of CD69 compared with
      controls. CD11b was also increased in BP blood eosinophils, which may explain the
      striking accumulation of eosinophils in BP (1*106 per ml blister fluid).
      Furthermore, CCL26 was expressed by activated eosinophils in BP skin and in
      blister fluid. BP eosinophils also released IL-6, IL-8 and IL-1alpha in BP
      blister fluids. Apoptosis in cultivated BP eosinophils was increased and
      accompanied by enhanced surface externalization of CD95. Caspase 3 positive
      eosinophils in lesional BP skin and blister fluid also showed the initiation of
      apoptosis. These results reveal novel pathophysiological aspects of BP, with a
      strong activation pattern and increased apoptosis of eosinophils in the
      peripheral blood, skin and blister fluids.

PMID- 27868138
TI  - PD-1 Antibody-induced Guillain-Barre Syndrome in a Patient with Metastatic
      Melanoma.

PMID- 27868141
TI  - Erythematous Grouped Papules and Plaque on an Intra-articular Injection Area: A
      Quiz.

PMID- 27868140
TI  - Psoriasis as a Manifestation of an Immune Reconstitution in Two Patients with
      Hepatitis C Treated with Ledipasvir/Sofosbuvir.

PMID- 27868139
TI  - Clinical, Genetic and Innate Immunity Characteristics of Melanoma in Organ
      Transplant Recipients.
AB  - The aims of this study were to determine the clinical and histological
      characteristics of melanoma in transplant recipients, the mutation profile (BRAF,
      NRAS and c-KIT genes), and the immune tolerance of the tumour microenvironment by
      immunohistochemical study of the expression of indoleamine 2,3-dioxygenase (IDO),
      PD1, PD-L1, CD8 and FoxP3. The study population comprised patients who had
      undergone a renal transplant in Nantes University Hospital who developed post
      transplantation melanoma. Twenty cases of melanoma out of 4,663 transplant
      recipients were studied. The results differed from the usual data with respect to
      melanoma site: 40% were located on the face and were of the malignant lentigo
      type. The mutation profile was concordant with that of the immunocompetent
      population. IDO was expressed in all the sections tested, while CD8, FoxP3, PD1
      and PD-L1 were poorly expressed. This reflected a highly immunodepressed tumour
      environment, raising the question of the inductive role of IDO on tumour immune
      tolerance in patients presenting with long-term immunodepression.

PMID- 27868142
TI  - A Japanese Case of Ichthyosiform Erythroderma with a Novel Mutation in
      NIPAL4/Ichthyin.

PMID- 27868143
TI  - Impact of Gliding on the Prevalence of Keratinocyte Carcinoma and its Precursors:
      A Cross-sectional Study Among Male Pilots in Bavaria.

PMID- 27868144
TI  - Paediatric Erythema Multiforme: Epidemiological, Clinical and Laboratory
      Characteristics.
AB  - Erythema multiforme (EM) is an immune-mediated reaction presenting as acrofacial
      target lesions. Most studies utilize the outdated classification, which includes
      EM, Stevens-Johnson syndrome and toxic epidermal necrolysis as related entities.
      We describe here epidemiological, aetiological, clinical, laboratory and
      treatment characteristics of paediatric EM. This is a retrospective single-centre
      study, performed between 2000 and 2013. Of 119 children given a diagnosis of EM,
      only 30 met clinical criteria and were included in this study. Most misdiagnosed
      cases were non-specific eruptions and urticaria multiforme. Mean age was 11.3
      years. Fifty percent had mucosal involvement. An aetiology was observed in half
      of the patients. Seventy percent of patients were admitted to hospital, 46.7%
      were treated with systemic steroids. Sixteen percent had recurrent EM. The most
      common identified infectious agent associated with EM in this study was
      Mycoplasma pneumonia and the cases associated with this infection may represent
      the recent entity, mycoplasma-induced rash and mucositis. Association with herpes
      simplex virus was not observed. Despite being a benign, self-limiting condition,
      children were over-treated in terms of hospitalization and therapy.

PMID- 27868145
TI  - Adalimumab Dose Tapering in Psoriasis: Predictive Factors for Maintenance of
      Complete Clearance.
AB  - Psoriasis can be managed successfully with long-term biologics. Real-life
      clinical practice may require dose tapering as a therapeutic option to reduce the
      risk of drug-exposure and to increase cost-effectiveness. The responsiveness to
      extended intervals between adalimumab doses and the possible predictive factors
      of maintenance of complete clearance were studied in a retrospective 7-year
      single-centre analysis. Thirty patients who achieved complete clearance with
      adalimumab underwent dose tapering, progressively extending between-dose
      intervals (to 21-28 days). Sixty percent of subjects (group A) maintained
      complete clearance, whereas 40.0% (group B) relapsed and were switched back to
      the standard dosage to re-achieve complete clearance. Body mass index (BMI) and
      time to achieve Psoriasis Area Severity Index (PASI-100) with adalimumab standard
      treatment before dose tapering were significantly lower in group A than in group
      B (multi-variate Cox regression: p < 0.05, Kaplan-Meier analysis: p < 0.001,
      respectively). This study suggests that patients with lower BMI and shorter time
      to achieve PASI-100 with adalimumab standard dose were significantly more likely
      to be candidates for dose tapering.

PMID- 27868146
TI  - Positive Association Between Vitamin D Serum Levels and Naevus Counts.
AB  - Lower vitamin D serum levels are linked to increased melanoma risk and poorer
      survival. Naevus counts are associated with both melanoma risk and survival and
      to leucocyte telomere length. Vitamin D is also linked to telomere biology with
      higher levels of vitamin D in individuals with longer leucocyte telomere length
      despite adjusting for age. Using the TwinsUK data, we explored the association
      between naevus count, leucocyte telomere length and vitamin D serum levels.
      Increasing vitamin D levels were associated with increasing naevus count: serum
      levels were 73.3 nmol/l in individuals with less than 50 naevi compared to 78.8
      nmol/l in individuals with more than 50 naevi (p?=?0.002). In the final
      regression model, using naevus count as a continuous variable, vitamin D remained
      associated with higher naevus counts despite adjustment for age, weight, height,
      season of sampling and twin relatedness (p?=?0.02). Further adjustment for
      leucocyte telomere length, decreased the magnitude of the association but it
      remained significant so leucocyte telomere length is not the sole driver of this
      association. Having large numbers of naevi is associated with higher vitamin D
      serum levels.

PMID- 27868148
TI  - The "Alarmins" HMBG1 and IL-33 Downregulate Structural Skin Barrier Proteins and
      Impair Epidermal Growth.
AB  - The epidermal-derived "alarmins" high-mobility group box 1 (HMGB1) protein and
      interleukin-33 (IL-33) are upregulated in patients with atopic dermatitis. How
      ever, their capacity as pro-inflammatory cytokines and their derived effects on
      skin barrier regulation are poorly elucidated. We investigated the impact of
      HMGB1 and IL-33 on gene transcription, protein expression and epidermal
      differentiation across 3 distinct keratinocyte in vitro models. Primary
      keratinocytes from healthy donors were used in submerged monolayer cultures, 3D
      human epidermis equivalents and 3D human skin equivalents. All keratinocyte
      models underwent 96-h stimulation with HMGB1 (100 MUM) or IL-33 (100 ng/ml) using
      IL-4 (50 ng/ml) as positive control of regulation and vehicle as negative
      control. We found that HMGB1 and IL-33 downregulated transcription of several
      genes from members of the epidermal differentiation complex, including filaggrin.
      Furthermore, HMGB1 downregulated the expression of the encoded proteins in the
      upper epidermis. Finally, IL-33 and HMGB1 ultimately led to impaired epidermal
      growth and maturation. In conclusion, HMGB1 and IL-33 could play a significant
      role in the atopic dermatitis pathophysiology due to negative regulation of
      structural proteins, stratum corneum formation and epidermal growth.

PMID- 27868147
TI  - Congenital Ichthyosis and Recurrent Eczema Associated with a Novel ALOXE3
      Mutation.

PMID- 27868149
TI  - Topical Carmustine as Monotherapy or as Multimodality Therapy for Folliculotropic
      Mycosis Fungoides.

PMID- 27868151
TI  - Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss) Relapsing as
      Bullous Eruption.

PMID- 27868150
TI  - Clinical Efficiency of Topical Calcipotriol/Betamethasone Treatment in Psoriasis
      Relies on Suppression of the Inflammatory TNFalpha - IL-23 - IL-17 Axis.
AB  - The effects of topical calcipotriol/betamethasone combination therapy and
      betamethasone monotherapy on inflammatory T-cell numbers and molecular markers
      were compared in patients with psoriasis. Combination therapy down-regulated the
      expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-23A, IL-17A,
      S100A7, CCL-20 and interferon (IFN)-gamma in skin and TNF-alpha, IL-6, IL-23A, T
      bet and IFN-gamma in peripheral blood mononuclear cells (PBMCs). Betamethasone
      monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down
      regulated by calcipotriol/betamethasone, but not by betamethasone.
      Immunohistochemical analysis revealed that calcipotriol/betamethasone reduced the
      numbers of CD4+ and CD8+ T cells and Tregs in psoriatic lesions more than
      betamethasone. Flow cytometric analyses demonstrated that
      calcipotriol/betamethasone decreased the numbers of circulating CD8+ T cells,
      Tregs, skin-homing Th17 memory cells and Th22 memory cells, while betamethasone
      had little or no effect. Glucocorticoid receptors GRalpha and GRbeta were
      expressed in psoriatic skin. In conclusion, calcipotriol increases the
      immunosuppressive power of betamethasone by suppressing the inflammatory TNF
      alpha - IL-23 - IL-17 axis.

PMID- 27868154
TI  - Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis.
AB  - This review summarises the recent findings on metabolic treatments for epilepsy
      and Amyotrophic Lateral Sclerosis (ALS) in honour of Professor Ursula Sonnewald.
      The metabolic impairments in rodent models of these disorders as well as affected
      patients are being discussed. In both epilepsy and ALS, there are defects in
      glucose uptake and reduced tricarboxylic acid (TCA) cycling, at least in part due
      to reduced amounts of C4 TCA cycle intermediates. In addition there are
      impairments in glycolysis in ALS. A reduction in glucose uptake can be addressed
      by providing the brain with alternative fuels, such as ketones or medium-chain
      triglycerides. As anaplerotic fuels, such as the triglyceride of heptanoate,
      triheptanoin, refill the TCA cycle C4/C5 intermediate pool that is deficient,
      they are ideal to boost TCA cycling and thus the oxidative metabolism of all
      fuels.

PMID- 27868155
TI  - Hepatic Collision Tumor of Metastatic Pancreatic Adenocarcinoma and Chronic
      Lymphocytic Leukemia: A Case Report.

PMID- 27868153
TI  - Carnosine Attenuates Brain Oxidative Stress and Apoptosis After Intracerebral
      Hemorrhage in Rats.
AB  - Carnosine, an endogenous dipeptide (beta-alanyl-L-histidine), exerts multiple
      neuroprotective properties, but its role in intracerebral hemorrhage (ICH)
      remains unclear. This study investigates the effect of Carnosine on brain injury
      using the rat ICH model, which is established by type IV collagenase caudatum
      infusion. The results indicate that intraperitoneal administration of Carnosine
      (1000 mg/kg) significantly attenuates brain edema, blood-brain barrier (BBB)
      disruption, oxidative stress, microglia activation and neuronal apoptosis of
      perihematoma at 72 h following ICH in rats models, as convinced by preventing the
      disruption of tight junction protein ZO-1, occludin and claudin-5, followed by
      the decrease of ROS, MDA, 3-NT, 8-OHDG level and the increase of GSH-Px and SOD
      activity, then followed by the decline of Iba-1, ED-1, active caspase-3 and TUNEL
      positive cells and the decrease of IL-1beta, IL-6, TNF-alpha, active caspase-3
      and cytochrome c level. Our results suggest that Carnosine may provide
      neuroprotective effect after experimental ICH in rat models.

PMID- 27868152
TI  - Effect of buffalo casein-derived novel bioactive peptides on osteoblast
      differentiation.
AB  - PURPOSE: Epidemiological and intervention studies show that milk consumption in
      childhood and during adolescence is related to higher bone mineral density. Milk
      and milk products prevent the bone loss in pre- and postmenopausal women. Apart
      from calcium, there are other biologically active compounds in milk such as
      bioactive peptides which may play a role in promoting bone health. Casein is the
      major protein in milk which has also been reported to have numerous biological
      active peptides within it. The hypothesis of the present study was to identify
      the key peptides behind osteoanabolic nature of the milk protein, which further
      can be used to prepare functional foods to alleviate bone diseases like
      osteoporosis. Hence, this study was carried out to investigate osteogenic nature
      of four novel bioactive peptides [PEP1 (EDVPSER), PEP2 (NAVPITPTL), PEP3
      (VLPVPQK) and PEP4 (HPHPHLSF)] derived from buffalo casein by in vitro osteoblast
      differentiation model. METHODS: Calvaria cells were isolated from 3-day-old rat
      pups, cultured under in vitro conditions till confluence and further used for
      experiments. Calvarial osteoblast cells were cultured in the presence or absence
      of peptides including positive controls up to 21 days. Effect of peptides was
      checked at regular intervals by quantifying osteoblast differentiation marker
      genes (ALP, OCN and COL-1) expression, alkaline phosphatase activity, osteocalcin
      level in culture supernatants, mineral deposition by alizarin red staining and
      caspase-3 and 9 assays. RESULTS: The osteoblast differentiation marker genes
      (ALP, OCN and COL-1) expression was significantly [(p < 0.01) (p < 0.001)] up
      regulated in the presence of these peptides. The peptides also significantly
      induced alkaline phosphatase activity, osteocalcin level and mineral deposition
      in comparison with the control. It was also observed that all the four peptides
      did not show any cytotoxic effect during 21-day treatment period. CONCLUSION: All
      peptides enhanced osteoblast differentiation along with the positive controls.
      These results hold an immense scope to use peptides as preventive measure for
      reducing incidence of osteoporosis. These peptides can also be used as drugs and
      can be utilized as functional ingredients in functional foods preparation for
      osteoporosis therapy, but in vivo studies are required for further confirmation.

PMID- 27868156
TI  - Vaginal and sexual health treatment strategies within a female sexual medicine
      program for cancer patients and survivors.
AB  - PURPOSE: We sought to evaluate patient adherence and response to simple vaginal
      and sexual health treatment strategies in female cancer patients receiving
      treatment at a female sexual medicine and health program and identify
      improvements of physical symptoms, per patient and clinical evaluation. METHODS:
      Evaluability criteria included gynecologic exam at initial visit, at least one
      follow-up with gynecologic exam within 8 months of initial visit, and all
      consecutive follow-ups <6 months apart. Demographics, medical information, and
      clinical assessments from 175 evaluable patients with at least one follow-up from
      09/12 to 10/14 were analyzed. The majority of patients were being treated for or
      had a history of breast (n = 90, 53 %), gynecologic (n = 54, 32 %), or
      colorectal/anal (n = 15, 9 %) cancers. An assessment form included a clinician
      evaluation, Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), and
      patient-reported outcomes. Compliance with treatment recommendations were
      summarized, and changes over time were compared for clinical outcomes. RESULTS:
      Mean number of visits was 3.43. Mean age was 55.4 years; 92 % (n = 155/169) were
      in menopause. Treatment strategies included rationale and instruction for use of
      vaginal moisturizers, lubricants, pelvic floor exercises, and dilator therapy, in
      addition to psychosexual education regarding sexual changes (response, anatomy,
      and function) associated with cancer treatment and support. At last assessment,
      89 % had complied with the clinical recommendation (moisturize 2-5+ times/week).
      Vaginal pH scores >6.5 declined over time (p = 0.03). VAS scores improved by last
      assessment (p < 0.001), as did VuAS scores (p = 0.001). Sexual function scores
      significantly improved (p < 0.001), confidence about future sexual activity
      increased (p = 0.004), and sexual/vaginal health concerns decreased (p =
      0.00003). CONCLUSION: Significant changes were observed in women using treatment
      strategies, with improvement in vulvovaginal symptoms, a decrease in elevated
      vaginal pH and pain with exams, enhanced sexual function, and increased intimacy
      confidence. IMPLICATIONS FOR CANCER SURVIVORS: These findings have high clinical
      relevance for symptom management with improvement of sexual function using simple
      strategies and clinical tools in the oncology setting.

PMID- 27868157
TI  - MCM7 expression is a promising predictor of recurrence in patients surgically
      resected for meningiomas.
AB  - Patients with high risk of recurrence after meningioma resection might benefit
      from adjuvant radiation therapy and closer clinical follow-up. While the World
      Health Organization (WHO) classification and the MIB-1 biomarker are applied in
      the clinical practice to identify these patients, the reliability of these
      methods is questionable. To improve the prediction of tumor recurrence, this
      study evaluated and compared the prognostic usefulness of the biomarker MCM7 with
      the conventional mitotic index and the MIB-1 biomarker. One hundred sixty
      patients were retrospectively analyzed. The expression of MIB-1 and MCM7 was
      determined as proliferative indices (PI-percentage of positive immunoreactive
      cells among 1000 tumor cells) in tissue microarrays. MCM7 PI revealed
      significantly higher indices in recurrent meningiomas compared with non-recurrent
      meningiomas (p = 0.020), while mitotic index and MIB-1 PI did not reach
      statistical significance (p >= 0.547). The optimal cutoff values for recurrence
      prediction were 3% for MIB-1 PI and 8% for MCM7 PI. MCM7 PI was significantly
      associated with recurrence-free survival in COX multivariate survival analyses (p
      = 0.005), while no association was found with mitotic index or MIB-1 (p >=
      0.153). MCM7 PI allowed for the most accurate prediction of recurrence, obtaining
      the highest sensitivity and the greatest area under the ROC curve. These results
      proved that MCM7 PI is a better method for identifying patients with risk of
      recurrence compared with the traditional methods used in the current clinical
      practice. MCM7 may thus improve diagnostics, prediction of prognosis and
      treatment decision making in patients suffering from meningiomas.

PMID- 27868159
TI  - Are aphid parasitoids from mild winter climates losing their winter diapause?
AB  - Temperature is both a selective pressure and a modulator of the diapause
      expression in insects from temperate regions. Thus, with climate warming, an
      alteration of the response to seasonal changes is expected, either through
      genetic adaptations to novel climatic conditions or phenotypic plasticity. Since
      the 1980s in western France, the winter guild of aphid parasitoids (Hymenoptera:
      Braconidae) in cereal fields has been made up of two species: Aphidius
      rhopalosiphi and Aphidius matricariae. The recent activity of two other species,
      Aphidius avenae and Aphidius ervi, during the winter months suggests that a
      modification of aphid parasitoid overwintering strategies has taken place within
      the guild. In this study, we first performed a field survey in the winter of
      2014/15 to assess levels of parasitoid diapause incidence in agrosystems. Then,
      we compared the capacity of the four parasitoid species to enter winter diapause
      under nine different photoperiods and temperature conditions in the laboratory.
      As predicted, historically winter-active species (A. rhopalosiphi and A.
      matricariae) never entered diapause, whereas the species more recently active
      during winter (A. avenae and A. ervi) did enter diapause but at a low proportion
      (maximum of 13.4 and 11.2%, respectively). These results suggest rapid shifts
      over the last three decades in the overwintering strategies of aphid parasitoids
      in Western France, probably due to climate warming. This implies that diapause
      can be replaced by active adult overwintering, with potential consequences for
      species interactions, insect community composition, ecosystem functioning, and
      natural pest control.

PMID- 27868158
TI  - Growth and prevalence of feeding difficulties in children with Robin sequence: a
      retrospective cohort study.
AB  - OBJECTIVES: In addition to breathing problems, patients with Robin sequence (RS)
      often encounter feeding difficulties (FD). Data regarding the occurrence of FD
      and possible influencing factors are scarce. The study aim was to elucidate these
      factors to improve treatment strategies. MATERIAL AND METHODS: A retrospective
      comparative cohort study was conducted, consisting of 69 infants diagnosed with
      both RS and a cleft palate and 64 isolated cleft palate only (iCPO) infants. Data
      regarding FD, growth, and airway intervention were collected during the first 2
      years of life. A systematic review of the literature was conducted to identify
      reported FD in RS patients. RESULTS: RS patients had more FD (91 %) than iCPO
      patients (72 %; p = 0.004). Also, nasogastric (NG)-tube feeding was necessary
      more frequently and for a longer period (both p < 0.001). Growth was lower in RS
      than iCPO infants (p = 0.008) and was not affected by the kind of airway
      management (conservative/surgical; p = 0.178), cleft palate grade (p = 0.308), or
      associated disorders (p = 0.785). By contrast, surgical intervention subtype did
      significantly affect growth. Mean reported FD for RS in the literature is 80 %
      (range = 47-100 %), and 55 % (range = 11-100 %) of infants need NG-tube feeding.
      CONCLUSIONS: FD is present in a large proportion of infants with RS, which
      indicates the need for early recognition and proper treatment to ensure optimal
      growth. Growth during the first 2 years of life is significantly lower in RS
      patients than iCPO patients, which indicates the need for careful attention and
      long-term follow-up. CLINICAL RELEVANCE: This study indicates the need for early
      recognition and proper treatment of FD in RS to ensure optimal growth. In
      addition, growth needs careful attention and long-term follow-up.

PMID- 27868160
TI  - Severe changes in colon epithelium in the Mecp2-null mouse model of Rett
      syndrome.
AB  - BACKGROUND: Rett syndrome is best known due to its severe and devastating
      symptoms in the central nervous system. It is produced by mutations affecting the
      Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for
      MECP2 activity has been reported for tissues other than those of the central
      nervous system. Patients affected by Rett presented with intestinal affections
      whose origin is still not known. We have observed that the Mecp2-null mice
      presented with episodes of diarrhea, and decided to study the intestinal
      phenotype in these mice. METHODS: Mecp2-null mice or bearing the conditional
      intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of
      intestine, and RT-PCR, western blot and immunodetection were perfomed on
      intestinal samples of the animals. Electrical parameters of the intestine were
      determined by Ussing chamber experiments in freshly isolated colon samples.
      RESULTS: First we determined that MECP2 protein is mainly expressed in cells of
      the lower part of the colonic crypts and not in the small intestine. The colon of
      the Mecp2-null mice was shorter than that of the wild-type. Histological analysis
      showed that epithelial cells of the surface have abnormal localization of key
      membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral
      NaCl absorption; nevertheless, electrogenic secretion and absorption remain
      unaltered. We also detected an increase in a proliferation marker in the crypts
      of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2
      from intestinal epithelium was not able to recapitulate the intestinal phenotype
      of the Mecp2-null mice. CONCLUSIONS: In summary, we showed that the colon is
      severely affected by Mecp2 silencing in mice. Changes in colon length and
      epithelial histology are similar to those observed in colitis. Changes in the
      localization of proteins that participate in fluid absorption can explain watery
      stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce
      colon changes observed in the Mecp2-null mice, indicating the participation of
      other cells in this phenotype and the complex interaction between different cell
      types in this disease.

PMID- 27868164
TI  - Efficient production of recombinant glycoprotein D of herpes simplex virus type 2
      in Pichia pastoris and its protective efficacy against viral challenge in mice.
AB  - Herpes simplex virus type 2 (HSV-2) infection is the leading cause of genital
      ulcer disease and a significant public health concern. However, there are no
      approved vaccines available to prevent HSV-2 infection. The glycoprotein D (gD)
      of HSV-2 is the most important candidate antigen for vaccine development. In this
      study, a truncated form of gD (codons 1-340, gD1-340) was produced as a secretory
      protein in the methylotrophic yeast Pichia pastoris. The recombinant gD1-340 with
      a His6 tag was purified to homogeneity by one-step affinity chromatography. Mice
      immunized with the recombinant gD1-340 developed high levels of antigen-specific
      antibody responses with HSV-2 neutralizing activity. Immunization with the
      recombinant gD1-340 conferred significant protection against lethal HSV-2
      infection in mice. Moreover, measurement of the secretion of gD1-340-specific
      cytokines demonstrated that the recombinant gD1-340 induced mixed Th1/Th2
      cellular immune responses. These findings indicated that P. pastoris-derived gD1
      340 represents a promising HSV-2 vaccine candidate with strong immunogenicity and
      prophylactic efficacy.

PMID- 27868162
TI  - The choice of a constitutive formulation for modeling limb flexion-induced
      deformations and stresses in the human femoropopliteal arteries of different
      ages.
AB  - Open and endovascular treatments for peripheral arterial disease are notorious
      for high failure rates. Severe mechanical deformations experienced by the
      femoropopliteal artery (FPA) during limb flexion and interactions between the
      artery and repair materials play important roles and may contribute to poor
      clinical outcomes. Computational modeling can help optimize FPA repair, but these
      simulations heavily depend on the choice of constitutive model describing the
      arterial behavior. In this study finite element model of the FPA in the standing
      (straight) and gardening (acutely bent) postures was built using computed
      tomography data, longitudinal pre-stretch and biaxially determined mechanical
      properties. Springs and dashpots were used to represent surrounding tissue forces
      associated with limb flexion-induced deformations. These forces were then used
      with age-specific longitudinal pre-stretch and mechanical properties to obtain
      deformed FPA configurations for seven age groups. Four commonly used invariant
      based constitutive models were compared to determine the accuracy of capturing
      deformations and stresses in each age group. The four-fiber FPA model most
      accurately portrayed arterial behavior in all ages, but in subjects younger than
      40 years, the performance of all constitutive formulations was similar. In older
      subjects, Demiray (Delfino) and classic two-fiber Holzapfel-Gasser-Ogden
      formulations were better than the Neo-Hookean model for predicting deformations
      due to limb flexion, but both significantly overestimated principal stresses
      compared to the FPA or Neo-Hookean models.

PMID- 27868165
TI  - Effects of deletion of the ac109 gene of Autographa californica
      nucleopolyhedrovirus on interactions with mammalian cells.
AB  - Baculoviruses are able to enter into mammalian cells, where they can express a
      transgene that is placed under an appropriate promoter, without producing
      infectious progeny. ORF109 encodes an essential baculovirus protein that
      participates in the interaction of the baculovirus with mammalian cells. To date,
      the mechanisms underlying this interaction are not yet known. We demonstrated
      that although a Ac109 knock out virus maintained its ability to enter into BHK-21
      cells, there was a marked reduction in the expression efficiency of the nuclear
      transgene. Moreover, the amount of free cytoplasmic viral DNA, which was detected
      by transcription of a reporter gene, was severely diminished. These results
      suggest Ac109 could be involved in maintaining the integrity of the viral nucleic
      acid.

PMID- 27868163
TI  - Parents Perceive Improvements in Socio-emotional Functioning in Adolescents with
      ASD Following Social Skills Treatment.
AB  - The current study examined the effectiveness of a social skills treatment (PEERS)
      for improving socio-emotional competencies in a sample of high-functioning
      adolescents with ASD. Neuropsychological and self- and parent-report measures
      assessing social, emotional, and behavioral functioning were administered before
      and after treatment. Following social skills treatment, adolescents with ASD
      exhibited decreased aggression, anxiety, and withdrawal, as well as improvements
      in emotional responsiveness, adaptability, leadership, and participation in
      activities of daily living, though no change was found in affect recognition
      abilities. These findings suggest that PEERS social skills treatment improves
      particular aspects of emotional, behavioral, and social functioning that may be
      necessary for developing and maintaining quality peer relationships and
      remediating social isolation in adolescents with ASD.

PMID- 27868166
TI  - The Use of E-cigarettes Among School-Going Adolescents in a Predominantly Rural
      Environment of Central Appalachia.
AB  - E-cigarette use among youth in the United States (U.S.) continues to increase. In
      the rural Northeast Tennessee, where prevalence of tobacco use is higher than
      national and state averages, there is no literature on e-cigarette use to inform
      policies and programs. This study aimed to estimate the prevalence of e-cigarette
      use and examine association of e-cigarette use with two tobacco products among
      school-going adolescents. Data from 894 participants of a school-based survey
      conducted in 2016 in Northeast Tennessee were analyzed. Descriptive statistics
      and logistic regression analyses were conducted to estimate the prevalence and
      delineate the associations between e-cigarette use and other tobacco products.
      Approximately 11% of the participants currently used e-cigarettes, and 35% had
      ever used e-cigarettes. About 6% of the participants were current users of both e
      cigarettes and cigarettes; 4% were current users of e-cigarettes and smokeless
      tobacco; 3% were current users of all three products, and 15% had ever tried all
      three products. More than one-half of current e-cigarette users (52%) also smoked
      cigarettes. Adjusting for covariates, current e-cigarette use was positively
      associated with cigarette smoking [Odds Ratio (OR) 27.32, 95% confidence interval
      (CI) 14.4-51.7] and smokeless tobacco use [OR 7.92, 95% CI 3.8-16.5]. E-cigarette
      use was more common among the high school students than cigarette and smokeless
      tobacco use, and a significant proportion of users either smoked cigarettes, used
      smokeless tobacco, or both. Thus, there is a critical need for preventive
      policies and programs to address dual and poly-use of these products.

PMID- 27868161
TI  - Neutrophil plasticity enables the development of pathological microenvironments:
      implications for cystic fibrosis airway disease.
AB  - INTRODUCTION: The pathological course of several chronic inflammatory diseases,
      including cystic fibrosis, chronic obstructive pulmonary disease, and rheumatoid
      arthritis, features an aberrant innate immune response dominated by neutrophils.
      In cystic fibrosis, neutrophil burden and activity of neutrophil elastase in the
      extracellular fluid have been identified as strong predictors of lung disease
      severity. REVIEW: Although neutrophils are generally considered to be rigid, pre
      programmed effector leukocytes, recent studies suggest extensive plasticity in
      how neutrophil functions unfold upon recruitment to peripheral tissues, and how
      they choose their ultimate fate. Indeed, upon migration to cystic fibrosis
      airways, neutrophils display dysregulated lifespan, metabolic activation, and
      altered effector and regulatory functions, consistent with profound adaptation
      and phenotypic reprogramming. Licensed by signals present in cystic fibrosis
      airway microenvironment to survive and develop these novel functions, neutrophils
      orchestrate, in partnership with the epithelium and with the resident microbiota,
      the evolution of a pathological microenvironment. This microenvironment is
      defined by altered proteolytic, redox, and metabolic balance and the presence of
      stable luminal structures in which neutrophils and microbes coexist. CONCLUSIONS:
      The elucidation of molecular mechanisms driving neutrophil plasticity in vivo
      will open new treatment opportunities designed to modulate, rather than block,
      the crucial adaptive functions fulfilled by neutrophils. This review aims to
      outline emerging mechanisms of neutrophil plasticity and their participation in
      the building of pathological microenvironments in the context of cystic fibrosis
      and other diseases with similar features.

PMID- 27868167
TI  - The role of Ugandan District Hospital orthopedic units in the care of vulnerable
      road users: a cross-sectional study.
AB  - BACKGROUND: Musculoskeletal injuries are a common cause of morbidity after road
      traffic injury (RTI) in motorizing countries. District hospitals provide front
      line orthopedic care in Uganda and other sub-Saharan African nations. Improving
      care at the district hospital level is an important component of the World Health
      Organization's strategy for surgical and trauma systems strengthening, but the
      data necessary to inform RTI safety and care initiatives has previously been
      insufficient at the district hospital level. The objective of this study was to
      provide data on the patient population and patterns of musculoskeletal injury
      caused by RTI at Ugandan district hospitals. METHODS: In this cross-sectional
      study, all patients with musculoskeletal injuries identified on x-ray presenting
      to three Ugandan district hospitals from October 2013 to January 2014 were
      interviewed and examined to obtain data on patient demographics and injury
      context by road user category. This manuscript is a sub-group analysis of RTI
      victims from a broader dataset of all musculoskeletal injuries. RESULTS:
      Vulnerable road users comprised 92 % of musculoskeletal RTI patients, with 49 %
      (95 % CI 41-57 %) pedestrians, 41 % (95 % CI 33-49 %) motorcyclists, and 2 % (95
      % CI 0-4 %) cyclists. Commonly injured subgroups included student pedestrians (33
      % (95 % CI 22-44 %) of pedestrians) and motorcyclists with less than a post
      secondary education (74 % (95 % CI 63-85 %) of motorcyclists). The morning hours
      were the most common time of injury for all RTI patients (37 %%; 95 % CI 30-44 %)
      and motorcyclists (46 %; 95 % CI 34-58 %), while pedestrians were most commonly
      injured in the evening (32 %; 95 % CI 21-43 %). CONCLUSIONS: By demonstrating
      commonly injured demographic groups and high frequency times of day for injury,
      this surveillance study of musculoskeletal RTI suggests targeted avenues for
      future road safety research in the districts of Uganda. Compared with previous
      studies from the capital of Uganda, these results suggest that Ugandan district
      hospitals care for a disproportionate share of vulnerable road users, a
      discrepancy which may pertain to other sub-Saharan African nations, as well.
      Strengthening district hospital orthopedic care should be considered a priority
      of strategies aimed at improving outcomes for these vulnerable groups.

PMID- 27868168
TI  - Use, perceptions, and benefits of automotive technologies among aging drivers.
AB  - Advanced in-vehicle technologies have been proposed as a potential way to keep
      older adults driving for as long as they can safely do so, by taking into account
      the common declines in functional abilities experienced by older adults. The
      purpose of this report was to synthesize the knowledge about older drivers and
      advanced in-vehicle technologies, focusing on three areas: use (how older drivers
      use these technologies), perception (what they think about the technologies), and
      outcomes (the safety and/or comfort benefits of the technologies). Twelve
      technologies were selected for review and grouped into three categories: crash
      avoidance systems (lane departure warning, curve speed warning, forward collision
      warning, blind spot warning, parking assistance); in-vehicle information systems
      (navigation assistance, intelligent speed adaptation); and other systems
      (adaptive cruise control, automatic crash notification, night vision enhancement,
      adaptive headlight, voice activated control). A comprehensive and systematic
      search was conducted for each technology to collect related publications. 271
      articles were included into the final review. Research findings for each of the
      12 technologies are synthesized in relation to how older adults use and think
      about the technologies as well as potential benefits. These results are presented
      separately for each technology. Can advanced in-vehicle technologies help extend
      the period over which an older adult can drive safely? This report answers this
      question with an optimistic "yes." Some of the technologies reviewed in this
      report have been shown to help older drivers avoid crashes, improve the ease and
      comfort of driving, and travel to places and at times that they might normally
      avoid.

PMID- 27868169
TI  - Articulatin-D induces apoptosis via activation of caspase-8 in acute T-cell
      leukemia cell line.
AB  - Leukemia is among the most aggressive and prevalent human malignant carcinoma.
      Chemotherapy is the preferred therapeutic strategy; however, recurrence of cancer
      and non-selective cytotoxicity are the major concerns. Unlike synthetic
      chemotherapeutic agents, mistletoe ribosome-inactivating protein (RIP) displays
      anti-tumor function in various types of cancers. However, its effect on leukemia
      cells is little explored. In this study, we assessed the impact of Viscum
      articulatum RIP (Articulatin-D) on the survival of acute T-cell leukemia cells
      and the involved molecular and cellular mechanisms. Cell proliferation assay
      showed that Articulatin-D suppressed the viability of leukemia cells selectively.
      We further confirmed that the elevation of mitochondrial membrane potential and
      exposure of phosphatidylserine are the early events of apoptosis induction in
      Articulatin-D-treated Jurkat cells. Subsequently, we found that Articulatin-D
      treatment induces apoptosis in Jurkat cells in a time- and concentration
      dependent manner. In conclusion, we provided evidence that Articulatin-D
      efficiently activates caspase-8 involved in extrinsic pathway of apoptosis
      induction, which ultimately results in caspase-3-dependent DNA fragmentation of
      Jurkat cells. Further evaluation of Articulatin-D in cell culture and animal
      models may provide novel information on selective cytotoxicity to acute T-cell
      leukemia and its involvement in targeting tumor cell survival pathways.

PMID- 27868171
TI  - [Confusion about confusion].

PMID- 27868172
TI  - [The validity of acute assessments of psychiatric conditions made by psychiatric
      emergency staff].
AB  - BACKGROUND: Earlier research carried out by the outreach psychiatric emergency
      team in the region of Uden / Veghel in the Netherlands indicated that the
      preliminary diagnosis of patients in crisis was associated with aggressive
      behaviour during the later contact between the patient and the staff of the
      psychiatric emergency team. An accurate diagnosis by the staff of the psychiatric
      emergency team is important because it should guide the patient towards the right
      type of treatment by the most appropriate team. The staff of the psychiatric
      emergency service who make the initial diagnosis are pressed for time and have
      only limited information.<br/> AIM: To find out what differences there are
      between the crisis team's initial diagnosis of the psychiatric condition of the
      patient in crisis and the later diagnosis made after more extensive psychiatric
      tests are carried out following the regular intake procedure.<br/> METHOD: Our
      study was based om 129 patients who, in the period of 2009 and 2010, were not
      known to mental health service and had not had any previous contact with the
      psychiatric emergency service. The first assessment of a patient's psychiatric
      condition made by a member of the psychiatric emergency service was compared with
      the later diagnosis made by a professional psychiatrist after the regular intake
      procedure. We then investigated the degree of agreement between the two diagnoses
      using Cohen's kappa so that we could test the validity of the initial screening
      of the patient's condition.<br/> RESULTS: We found that the staff of the
      psychiatric emergency team was able to achieve a result that was better than
      could be expected on the basis of chance. The Cohen's kappas varied between 0.81
      for psychotic disorders to 0.31 for borderline personality disorders. Borderline
      personality disorders, however, tended to be overestimated by the psychiatric
      emergency staff.<br/> CONCLUSION: Although there was only limited agreement
      regarding various conditions, it is encouraging that the psychiatric emergency
      staff were able to assess psychotic disorders accurately on the basis of the
      initial information they had received. This result is important because in other
      studies psychotic symptoms were found to be associated with a higher likelihood
      of aggression during the later outreach consultation.

PMID- 27868173
TI  - [Validation of tools for assessing the intelligence and the functional impairment
      of Papiamento speaking suspects].
AB  - BACKGROUND: Although Antillean suspects in the Netherlands are often diagnosed as
      being intellectually impaired, there are no validated tests available Papiamento
      (the native language) for assessing intelligence or functional impairment. AIM:
      To validate the use of the GIT 2 (Groninger Intelligentie Test 2) and the Barkley
      Functioning Impairment Scale (BFIS) for Antillean defendants detained by the
      Judicial Service of the Caribbean Netherlands in Bonaire. METHOD: With the
      approval of the publishers, the GIT 2 and the BFIS were translated in Papiamento
      by two independent experts. The two translations were then re-translated into
      Dutch by two other independent experts. Defendants with both parents born in
      Bonaire who had been detained for at least 18 days by the Judicial Detention
      Centre of the Caribbean Netherlands (JICN) in Bonaire during the period 1 January
      2013 until 1 July 2014 were examined with both tests. RESULTS: The Papiamento GIT
      2 and BFIS tests were taken by 23 Bonairian defendants who had been detained in
      the JICN in Bonaire. The internal consistency and inter-item correlation of the
      tests were found to be satisfactory. The IQ of 95% of the participants was
      reproduced as a score between 79.2 and 96.8 points. In the BFIS the question
      about self-care was a particularly sensitive item. The use of drugs was
      associated with increased functional impairment. CONCLUSION: This study seems to
      be a promising first step towards the validation of the GIT 2 and the BFIS.
      Apparently, it has now become acceptable to use written Papiamento in assessment
      tools.

PMID- 27868175
TI  - [The proportion of suicides committed by patients with a mental health disorder
      for which treatment costs are now no longer reimbursed by health insurance].
AB  - BACKGROUND: Suffering from a psychiatric disorder is a well-known risk factor for
      suicide and suicidal behavior. Treatment of psychiatric disorders can reduce the
      risk of suicidal behavior and suicide. In the Netherlands, however, since 2012
      the treatment costs of some psychiatric disorders have no longer been covered by
      health insurance.<br/> AIM: To find out what proportion of suicides were
      committed by patients with a psychiatric disorder for which treatment costs are
      no longer covered by health insurance since the rules changed in 2012.<br/>
      METHOD: We studied the files of 314 patients who were known to one of the large
      mental health hospitals in the Netherlands and who had committed suicide between
      1 January 1999 and January 2012. We were able to determine the various
      psychiatric disorders from which the patients were suffering at the time they
      died.<br/> RESULTS: About 6% of the patients who committed suicide between 1999
      and 2012 suffered from a psychiatric disorder for which treatment costs are now
      no longer covered by health insurance.<br/> CONCLUSION: Given the results of this
      study, the increased rates of suicide in the Netherlands and the importance of
      scientific research into the characteristics of suicide, we recommend that
      patients with suicidal behavior are not excluded from adequate treatment in the
      event they may or may not have met the criteria for a DSM-IV classification.

PMID- 27868174
TI  - [Acromegaly: recognition of a rare disease in psychiatric practice].
AB  - BACKGROUND: Acromegaly is a rare disease which is caused by a tumour in the
      anterior lobe of the pituitary gland. The tumour stimulates excessive production
      of the growth hormone. As a result, all the organs and tissues in the body are
      induced to grow. This growth is responsible for a wide range of symptoms, some of
      which can be neuro-psychiatric.<br/> AIM: To promote the early detection of
      acromegaly so that treatment can be started as soon as possible and further
      damage can be prevented.<br/> METHOD: We searched PubMed for articles relating to
      quality of life and cognitive, psychological and psychiatric symptoms and
      personality changes associated with acromegaly.<br/> RESULTS: We describe the
      pathophysiology and epidemiology of acromegaly. Then we present the
      characteristic, external changes, neuro-cognitive complications, psychiatric
      disorders, personality changes and relevant comorbid somatic symptoms. Acromegaly
      is a disease in which patients, long before being diagnosed, present with
      cognitive and affective disorders. Before patients are diagnosed, they have often
      visited several consultants in connection with their nonspecific symptoms.<br/>
      CONCLUSION: We believe that in everyday practice patients with acromegaly are
      frequently misdiagnosed. If patients present with extensive somatic co-morbidity
      and treatment-resistant depression and particularly if these symptoms are
      combined with the typical external features of acromegaly, then acromegaly can be
      suspected and further investigation should proceed without delay.

PMID- 27868176
TI  - [Mindfulness training for psychiatrists in residency: a pilot study].
AB  - BACKGROUND: Medical students and psychiatrists in residency run a high risk for
      burnout. Furthermore, while at medical school, students seem to experience a
      reduction in empathy; this seems to be linked to a high level of stress.
      Interventions based on mindfulness training appear to reduce stress and increase
      empathy in medical students. Trainees in psychiatric residency might also benefit
      from mindfulness training.<br/> AIM: To assess the effects that a mindfulness
      course has on perceived stress and empathy in psychiatrists in residency.<br/>
      METHOD: In this pilot study 13 trainees in psychiatric residency participated in
      an eight-week course in mindfulness. Before and after the training, 11 of the
      participants completed questionnaires relating to their empathy, perceived stress
      and mindfulness.<br/> RESULTS: Participants reported experiencing considerably
      more empathy after their course than before it. Perceived stress also diminished,
      but not significantly.<br/> CONCLUSION: The results support our suggestion that
      mindfulness training can be a valuable part of the curriculum for trainees in
      psychiatric residency.

PMID- 27868170
TI  - Protein kinases: mechanisms and downstream targets in inflammation-mediated
      obesity and insulin resistance.
AB  - Obesity-induced low-grade inflammation (metaflammation) impairs insulin receptor
      signaling. This has been implicated in the development of insulin resistance.
      Insulin signaling in the target tissues is mediated by stress kinases such as p38
      mitogen-activated protein kinase, c-Jun NH2-terminal kinase, inhibitor of NF-kB
      kinase complex beta (IKKbeta), AMP-activated protein kinase, protein kinase C,
      Rho-associated coiled-coil containing protein kinase, and RNA-activated protein
      kinase. Most of these kinases phosphorylate several key regulators in glucose
      homeostasis. The phosphorylation of serine residues in the insulin receptor and
      IRS-1 molecule results in diminished enzymatic activity in the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway. This has been one of the key
      mechanisms observed in the tissues that are implicated in insulin resistance
      especially in type 2 diabetes mellitus (T2-DM). Identifying the specific protein
      kinases involved in obesity-induced chronic inflammation may help in developing
      the targeted drug therapies to minimize the insulin resistance. This review is
      focused on the protein kinases involved in the inflammatory cascade and molecular
      mechanisms and their downstream targets with special reference to obesity-induced
      T2-DM.

PMID- 27868177
TI  - [Early use of memantine in the treatment of Lewy body dementia].
AB  - Early use of memantine in the treatment of Lewy body dementia (LBD) is a common
      type of major neurocognitive disorder (NCD), which is difficult to treat. The use
      of memantine can be an early treatment strategy. This is illustrated by a case of
      an 80-year-old patient whose cognition, motor skills and perception disorders
      reacted favourably to treatment with memantine. The beneficial effect, however,
      was soon lost after the treatment was discontinued, but reappeared after the
      medication was reintroduced.

PMID- 27868179
TI  - [Reaction on 'Mania induced by antibiotic therapy'].

PMID- 27868178
TI  - [Right to ROM? Right to privacy: ROM data are medical data].

PMID- 27868180
TI  - [Reaction on 'Patients without dsm-iv-disorders and/or subclinical symptoms in
      generalistic and specialised mental health care'].

PMID- 27868181
TI  - Correlation between the high expression levels of cancer-germline genes with
      clinical characteristics in esophageal squamous cell carcinoma.
AB  - Antigens encoded by cancer-germline genes are attractive targets for cancer
      immunotherapy. In this study, we aimed to evaluate the mRNA expression of cancer
      germline genes, expression of the encoded proteins in patients with esophageal
      squamous cell carcinoma (ESCC) and their correlations with clinical
      characteristics. In addition, the effects of downregulation cancer-germline genes
      on ESCC cells were assessed in vitro. Our results showed that cancer-germline
      genes were frequently expressed in ESCC samples. The positive rates of in ESCC
      samples were: 87% of MAGE-A3, 60% of MAGE-A4, 65% of MAGE-C2, and 20% of NY-ESO-1
      at mRNA level. MAGE-A3 expression was associated with age, lymph node metastasis
      and tumor stage (all P<0.05), while MAGE-C2 expression was only associated with
      tumor stage (P<0.05). Furthermore, the MAGE-A3 expressing patients had a poorer
      overall survival (P<0.05). Multivariate analysis identified MAGE-A3 as an
      independent poor prognostic marker in ESCC. In vitro assay, ESCC cell lines
      treated with specific siRNAs to down-regulate MAGE-A3 and MAGE-C2 resulted in
      decreased colony-formation and migration ability (P<0.05). Epithelial marker E
      cadherin was up-regulated in siRNA-MAGE-A3/C2 cells compared to controls, whereas
      mesenchymal markers Vimentin, N-cadherin and Slug were downregulated (all
      P<0.05), suggesting a role for MAGE-A3/C2 in ESCC metastasis through inducing
      epithelial-mesenchymal transition. The present study revealed that cancer
      germline genes and their encoded proteins were frequently expressed in ESCC tumor
      samples and were related to poor prognosis. Thus, cancer-germline genes may serve
      as useful biomarkers and potential targets for ESCC patients.

PMID- 27868182
TI  - Attachment and Temperament in the Early Life Course: A Meta-Analytic Review.
AB  - This meta-analytic review examines the association between early attachment
      (assessed at 1-5 years) and child temperament (assessed at birth-12 years), and
      compares the strength of this association with recently documented meta-analytic
      associations between early attachment and social competence, externalizing
      behavior, and internalizing symptoms. Based on 109 independent samples (N =
      11,440) of diverse socioeconomic and ethnic backgrounds, temperament was weakly
      associated with attachment (in)security (d = .14, CI [0.08, 0.19]) but modestly
      associated with resistant attachment (d = .30, CI [0.21, 0.40]). Temperament was
      not significantly associated with avoidant (d = .10, CI [-0.02, 0.19]) or
      disorganized (d = .11, CI [-0.03, 0.25]) attachment. Across developmental
      domains, early attachment security was more strongly associated with social
      competence and externalizing behaviors than internalizing symptoms and
      temperament.

PMID- 27868183
TI  - Hydroxychloroquine prescribing and monitoring practices among Irish
      dermatologists and rheumatologists.

PMID- 27868184
TI  - The use of intravenous immunoglobulins in Stevens-Johnson syndrome and toxic
      epidermal necrolysis: caution needed.

PMID- 27868185
TI  - Muir-Torre syndrome: multiple sebaceous neoplasms and visceral malignancy
      manifesting after cardiac transplantation and iatrogenic immunosuppression.

PMID- 27868186
TI  - Recurrence of Stevens-Johnson syndrome and toxic epidermal necrolysis in adults.

PMID- 27868187
TI  - Basic aspects of the pathogenesis and prevention of non-melanoma skin cancer in
      solid organ transplant recipients: a review.
AB  - INTRODUCTION: As numbers of transplant recipients and survival rates increase,
      the vulnerability of this population to several malignancies also rises. Non
      melanoma skin cancer (NMSC) carries the highest rates of morbidity and mortality
      in this population. To avoid these malignancies, it is necessary to identify
      particular risk factors in transplant recipients and to follow preventive
      protocols. METHODS: The MEDLINE and EMBASE databases were reviewed using as
      keywords the medical subject headings (MeSH) "transplantation", "skin neoplasm"
      and "prevention". The search was limited to clinical trials, randomized clinical
      trials and case-control studies conducted during the previous 20 years. RESULTS:
      The most important risk factors for the development of NMSCs in the transplant
      recipient population are cumulative ultraviolet radiation exposure, use of
      immunosuppressive agents (especially azathioprine as a photosensitizing agent)
      and infections by human papillomaviruses. The use of sun protection and retinoids
      were identified as possible protective factors. Other potential therapies, such
      as antioxidants, difluormethylornithine and cyclooxygenase-2 inhibitors, require
      further study. CONCLUSIONS: Patient risk factors for the development of NMSC
      should be reviewed during the transplant consultation. Individuals found to be at
      increased risk should undergo closer follow-up and preventive care counseling.
      This article proposes an algorithm for the prevention of NMSC.

PMID- 27868188
TI  - Patency of paediatric endotracheal tubes for airway instrumentation.
AB  - BACKGROUND: Airway exchange catheters (AEC) and fiberoptic bronchoscopes (FOB)
      for tracheal intubation are selected so that there is only a minimal gap between
      their outer and inner diameter of endotracheal tube (ETT) to minimize the risk of
      impingement during airway instrumentation. This study aimed to test the ease of
      passage of FOBs and AECs through paediatric ETT of different sizes and from
      different manufacturers when using current recommendations for dimensional
      equipment compatibility taken from text books and manufacturers information.
      METHODS: Twelve different brands of cuffed and uncuffed ETT sized ID 2.5 to 5.0
      mm were evaluated in an in vitro set-up. Ease of device passage as well as the
      locations of an impaired passage within the ETT were assessed. Redundant samples
      were used for same sized ETT and all measurements were triple-checked in
      randomized order. RESULTS: In total, 51 paired samples of uncuffed as well as
      cuffed paediatric ETT were tested. There were substantial differences in the ease
      of ETT passage concordantly for FOBs and AECs among different manufacturers, but
      also among the product lines from the same manufacturer for a given ID size.
      Restriction to passage most frequently was found near the endotracheal tube tip
      or as a gradually increasing resistance along the ETT shaft. CONCLUSIONS: Current
      recommendations for dimensional equipment compatibility AECs and FOBs with ETTs
      do not appear to be completely accurate for all ETT brands available. We
      recommend that specific equipment combinations always must be tested carefully
      together before attempting to use them in a patient.

PMID- 27868189
TI  - An evaluation of inpatient morbidity and critical care provision in Zambia.
AB  - The aim of this study was to objectively measure demand for critical care
      services in a southern African tertiary referral centre. We carried out a point
      prevalence study of medical and surgical admissions over a 48-h period at the
      University Teaching Hospital, Lusaka, recording the following: age; sex;
      diagnosis; Human Immunodeficiency Virus (HIV) status and National Early Warning
      Score. One-hundred and twenty medical and surgical admissions were studied. Fifty
      four patients (45%) had objective evidence of a requirement for critical care
      review and potential or probable admission to an intensive care unit, according
      to the Royal College of Physicians (UK) guidelines. A greater than expected HIV
      rate was also noted; 53 of 75 tested patients (71%). When applied to the
      estimated 17,496 annual acute admissions, this would equate to 7873 patients
      requiring critical care input annually at this hospital alone. In contrast to
      this demand, we identified 109 critical care beds nationally, and only eight at
      this institution.

PMID- 27868190
TI  - Intensive care medicine in rural sub-Saharan Africa.
AB  - We undertook an audit in a rural Ugandan hospital that describes the epidemiology
      and mortality of 5147 patients admitted to the intensive care unit. The most
      frequent admission diagnoses were postoperative state (including following
      trauma) (2014/5147; 39.1%), medical conditions (709; 13.8%) and traumatic brain
      injury (629; 12.2%). Intensive care unit mortality was 27.8%, differing between
      age groups (p < 0.001). Intensive care unit mortality was highest for neonatal
      tetanus (29/37; 78.4%) and lowest for foreign body aspiration (4/204; 2.0%).
      Intensive care unit admission following surgery (333/1431; 23.3%), medical
      conditions (327/1431; 22.9%) and traumatic brain injury (233/1431; 16.3%) caused
      the highest number of deaths. Of all deaths in the hospital, (1431/11,357; 12.6%)
      occurred in the intensive care unit. Although the proportion of hospitalised
      patients admitted to the intensive care unit increased over time, from 0.7% in
      2005/6 to 2.8% in 2013/4 (p < 0.001), overall hospital mortality decreased
      (2005/6, 4.8%; 2013/14, 4.0%; p < 0.001). The proportion of intensive care
      patients whose lungs were mechanically ventilated was 18.7% (961/5147). This
      subgroup of patients did not change over time (2006, 16%; 2015, 18.4%; p = 0.12),
      but their mortality decreased (2006, 59.5%; 2015, 44.3%; p < 0.001).

PMID- 27868191
TI  - Multigenerational Head Start Participation: An Unexpected Marker of Progress.
AB  - One-quarter of the Head Start population has a mother who participated in the
      program as a child. This study uses experimental Head Start Impact Study (HSIS)
      data on 3- and 4-year-olds (N = 2,849) to describe multigenerational Head Start
      families and their program experiences. In sharp contrast to full-sample HSIS
      findings, Head Start has large, positive impacts on cognitive and socioemotional
      development through third grade among the children of former participant mothers,
      including improved mathematics skills and reductions in withdrawn and aggressive
      behavior. Evidence suggests that differences in program impacts between single-
      and multigenerational Head Start families are driven largely by differences in
      family resources and home learning environments.

PMID- 27868192
TI  - The association between drugs and bullous pemphigoid.

PMID- 27868193
TI  - No Pattern Alteration in Single Nocturnal Melatonin Secretion in Patients With
      Hypnic Headache: A Case-Control Study.
AB  - OBJECTIVE: To investigate headache-related serum melatonin levels and melatonin
      excretion rhythmicity in patients with hypnic headache (HH). BACKGROUND: Strict
      sleep dependency of headache attacks is a pathognomonic feature of HH. Changes in
      melatonin levels, a marker for circadian rhythm, are assumed to play a pivotal
      role in the pathophysiology of HH. METHODS: Serum melatonin levels were acquired
      in nine patients with HH and nine age- and gender-matched healthy controls over a
      20-hour time period (12 pm, 4 pm, 7 pm, 10 pm, time of headache, and 8 am).
      RESULTS: No significant changes of melatonin levels could be detected comparing
      HH patients and healthy controls. Melatonin excretion rhythmicity was not
      significantly altered in patients with HH (Mean melatonin level in ng/mL +/- SD,
      patients vs controls at 12 pm: 21.5 +/- 9.5 vs 13.6 +/- 6.3 [P = .077], 4 pm:
      18.4 +/- 8.4 vs 14.0 +/- 4.7 [P = .222], 7 pm: 19.4 +/- 5.1 vs 15.1 +/- 4.5 [P =
      .094], 10 pm: 59.5 +/- 45.0 vs 29.4 +/- 12.7 [P =.136], headache time: 96.9 +/-
      68.3 vs 49.1 +/- 22.8 [P = .94], and 8 am: 31.6 +/- 18.3 vs 26.7 +/- 15.6 [P =
      .489]). CONCLUSION: This study is not able to confirm a significant role of
      melatonin concentration changes in the pathophysiology of HH and vetoes that
      melatonin deficiency plays a major role in the pathophysiology of the disorder.

PMID- 27868194
TI  - Randomized controlled trial of vitamin D supplementation in children with autism
      spectrum disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a frequent developmental disorder
      characterized by pervasive deficits in social interaction, impairment in verbal
      and nonverbal communication, and stereotyped patterns of interests and
      activities. It has been previously reported that there is vitamin D deficiency in
      autistic children; however, there is a lack of randomized controlled trials of
      vitamin D supplementation in ASD children. METHODS: This study is a double
      blinded, randomized clinical trial (RCT) that was conducted on 109 children with
      ASD (85 boys and 24 girls; aged 3-10 years). The aim of this study was to assess
      the effects of vitamin D supplementation on the core symptoms of autism in
      children. ASD patients were randomized to receive vitamin D3 or placebo for 4
      months. The serum levels of 25-hydroxycholecalciferol (25 (OH)D) were measured at
      the beginning and at the end of the study. The autism severity and social
      maturity of the children were assessed by the Childhood Autism Rating Scale
      (CARS), Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and
      the Autism Treatment Evaluation Checklist (ATEC). TRIAL REGISTRATION NUMBER: UMIN
      CTR Study Design: trial number: UMIN000020281. RESULTS: Supplementation of
      vitamin D was well tolerated by the ASD children. The daily doses used in the
      therapy group was 300 IU vitamin D3/kg/day, not to exceed 5,000 IU/day. The
      autism symptoms of the children improved significantly, following 4-month vitamin
      D3 supplementation, but not in the placebo group. This study demonstrates the
      efficacy and tolerability of high doses of vitamin D3 in children with ASD.
      CONCLUSIONS: This study is the first double-blinded RCT proving the efficacy of
      vitamin D3 in ASD patients. Depending on the parameters measured in the study,
      oral vitamin D supplementation may safely improve signs and symptoms of ASD and
      could be recommended for children with ASD. At this stage, this study is a single
      RCT with a small number of patients, and a great deal of additional wide-scale
      studies are needed to critically validate the efficacy of vitamin D in ASD.

PMID- 27868195
TI  - Predicting patterns of long-term adaptation and extinction with population
      genetics.
AB  - Population genetics struggles to model extinction; standard models track the
      relative rather than absolute fitness of genotypes, while the exceptions describe
      only the short-term transition from imminent doom to evolutionary rescue. But
      extinction can result from failure to adapt not only to catastrophes, but also to
      a backlog of environmental challenges. We model long-term adaptation to long
      series of small challenges, where fitter populations reach higher population
      sizes. The population's long-term fitness dynamic is well approximated by a
      simple stochastic Markov chain model. Long-term persistence occurs when the rate
      of adaptation exceeds the rate of environmental deterioration for some genotypes.
      Long-term persistence times are consistent with typical fossil species
      persistence times of several million years. Immediately preceding extinction,
      fitness declines rapidly, appearing as though a catastrophe disrupted a stably
      established population, even though gradual evolutionary processes are
      responsible. New populations go through an establishment phase where, despite
      being demographically viable, their extinction risk is elevated. Should the
      population survive long enough, extinction risk later becomes constant over time.

PMID- 27868197
TI  - Expression of a hepatitis B virus pre-S2 deletion mutant in the liver results in
      hepatomegaly and hepatocellular carcinoma in mice.
AB  - Hepatocellular carcinoma (HCC) is the most common form of liver cancer and has a
      poor prognosis and a low survival rate; its incidence is on the rise. Hepatitis B
      virus (HBV) infection is one of the main causes of HCC. A high prevalence of pre
      S deletions of HBV surface antigen, which encompass T-cell and/or B-cell
      epitopes, is found in HBV carriers; antiviral therapy and viral immune escape may
      cause and select for these HBV mutants. In particular, the presence of pre-S2
      deletion mutants is an important risk factor associated with cirrhosis and HCC.
      We generated Alb-preDeltaS2 transgenic mice that express a naturally occurring
      pre-S2 mutant protein containing a 33-nucleotide deletion (preDeltaS2); the aim
      was to investigate its effect on hepatocarcinogenesis. After 30 months of follow
      up, the liver pathology of the mice fell into four groups: G1, chronic
      inflammation solely; G2, chronic inflammation and fibrosis; G3, inflammation,
      fibrosis, and hepatomegaly accompanied by rectal prolapse (4-12%); and G4,
      hepatomegaly and spontaneous HCC (12-15%). Striking degeneration of the
      endoplasmic reticulum (ER) was present in the mouse livers at an early stage (4
      months old). At 8 months, overt ER stress and the Atf6 pathway of the unfolded
      protein response (UPR) were induced; at the same time, metabolic pathways
      associated with mevalonate and cholesterol biogenesis, involving the peroxisomes
      and the ER, were disturbed. At 20 months and older, the protein kinase RNA-like
      endoplasmic reticulum kinase (PERK) pathway of the UPR was induced and the Hippo
      transducer Yap was activated. Together, these ultrastructural aberrations and
      metabolic disturbance all seem to contribute to the molecular pathogenesis and
      hepatocarcinogenesis present in the Alb-preDeltaS2 mice. These findings may
      contribute to the development of therapies for the liver disorders and HCC
      associated with pre-S2 deletion mutations among HBV carriers. Copyright (c) 2016
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 27868198
TI  - First report of canine systemic cryptococcosis owing to Cryptococcus gattii in
      Europe.

PMID- 27868196
TI  - Differential regulation of blood flow-induced neovascularization and mural cell
      recruitment by vascular endothelial growth factor and angiopoietin signalling.
AB  - KEY POINTS: Combining nitric oxide (NO)-mediated increased blood flow with
      angiopoietin-1-Tie2 receptor signalling induces arteriolargenesis - the formation
      of arterioles from capillaries - in a model of physiological angiogenesis. This
      NO-Tie-mediated arteriolargenesis requires endogenous vascular endothelial growth
      factor (VEGF) signalling. Inhibition of VEGF signalling increases pericyte
      coverage in microvessels. Together these findings indicate that generation of
      functional neovasculature requires close titration of NO-Tie2 signalling and
      localized VEGF induction, suggesting that the use of exogenous VEGF expression as
      a therapeutic for neovascularization may not be successful. ABSTRACT: Signalling
      through vascular endothelial growth factor (VEGF) receptors and the tyrosine
      kinase with IgG and EGF domains-2 (Tie2) receptor by angiopoietins is required in
      combination with blood flow for the formation of a functional vascular network.
      We tested the hypothesis that VEGF and angiopoietin-1 (Ang1) contribute
      differentially to neovascularization induced by nitric oxide (NO)-mediated
      vasodilatation, by comparing the phenotype of new microvessels in the mesentery
      during induction of vascular remodelling by over-expression of endothelial nitric
      oxide synthase in the fat pad of the adult rat mesentery during inhibition of
      angiopoietin signalling with soluble Tie2 (sTie2) and VEGF signalling with
      soluble Fms-like tyrosine kinase receptor-1 (sFlt1). We found that NO-mediated
      angiogenesis was blocked by inhibition of VEGF with sFlt1 (from 881 +/- 98%
      increase in functional vessel area to 279 +/- 72%) and by inhibition of
      angiopoietin with sTie2 (to 337 +/- 67%). Exogenous angiopoietin-1 was required
      to induce arteriolargenesis (8.6 +/- 1.3% of vessels with recruitment of vascular
      smooth muscle cells; VSMCs) in the presence of enhanced flow. sTie2 and sFlt1
      both inhibited VSMC recruitment (both 0%), and VEGF inhibition increased pericyte
      recruitment to newly formed vessels (from 27 +/- 2 to 54 +/- 3% pericyte
      ensheathment). We demonstrate that a fine balance of VEGF and angiopoietin
      signalling is required for the formation of a functional vascular network.
      Endogenous VEGF signalling prevents excess neovessel pericyte coverage, and is
      required for VSMC recruitment during increased nitric oxide-mediated
      vasodilatation and angiopoietin signalling (NO-Tie-mediated arteriogenesis).
      Therapeutic vascular remodelling paradigms may therefore require treatments that
      modulate blood flow to utilize endogenous VEGF, in combination with exogenous
      Ang1, for effective neovascularization.

PMID- 27868200
TI  - Impact of Copayment Changes on Children's Albuterol Inhaler Use and Costs after
      the Clean Air Act Chlorofluorocarbon Ban.
AB  - OBJECTIVE: To examine changes in children's albuterol use and out-of-pocket (OOP)
      costs in response to increased copayments after the Food and Drug Administration
      banned inhalers with chlorofluorocarbon (CFC) propellants. SETTING: Four health
      maintenance organizations (HMOs), two that increased copayments for albuterol
      inhalers that went from generic CFC-containing to branded CFC-free versions, and
      two that retained generic copayments for CFC-free inhalers (controls). We
      included children with asthma aged 4-17 years with commercial coverage from 2007
      to 2010. DESIGN: Interrupted time series with comparison series. DATA: We
      obtained enrollee and plan characteristics from enrollment files, and utilization
      data from pharmacy and medical claims; OOP expenditures were extracted from
      pharmacy claims for two HMOs with cost data available. FINDINGS: There were no
      significant differences in albuterol use between the group with increased cost
      sharing and controls with respect to changes after the policy change. There was a
      postpolicy increase of $6.11 OOP per month per child using albuterol among those
      with increased cost-sharing versus $0.36 in controls; the difference between
      groups was significant (p < .01). CONCLUSIONS: Increased copayments for brand
      name CFC-free albuterol after the CFC ban did not lead to a decrease in
      children's albuterol use, but it led to a modest increase in OOP costs.

PMID- 27868201
TI  - Assembling activity/setting participation with disabled young people.
AB  - Rehabilitation research investigating activity participation has been largely
      conducted in a realist tradition that under-theorises the relationship between
      persons, technologies, and socio-material places. In this Canadian study we used
      a post-critical approach to explore activity/setting participation with 19 young
      people aged 14 to 23 years with complex communication and/or mobility
      impairments. Methods included integrated photo-elicitation, interviews, and
      participant observations of community-based activities. We present our results
      using the conceptual lens of assemblages to surface how different combinations of
      bodies, social meanings, and technologies enabled or constrained particular
      activities. Assemblages were analysed in terms of how they organised what was
      possible and practical for participants and their families in different contexts.
      The results illuminate how young people negotiated activity needs and desires in
      particular 'spacings' each with its own material, temporal, and social
      constraints and affordances. The focus on assemblages provides a dynamic analysis
      of how dis/abilities are enacted in and across geotemporal spaces, and avoids a
      reductive focus on evaluating the accessibility of static environmental features.
      In doing so the study reveals possible 'lines of flight' for healthcare,
      rehabilitation, and social care practices.

PMID- 27868202
TI  - Potential risks of orthodontic therapy: a critical review and conceptual
      framework.
AB  - This review examines some of the potential risks of orthodontic therapy along
      with their evidence base. The risks of orthodontic treatment include periodontal
      damage, pain, root resorption, tooth devitalization, temporomandibular disorder,
      caries, speech problems and enamel damage. These risks can be understood to arise
      from a synergy between treatment and patient factors. In general terms, treatment
      factors that can influence risk include appliance type, force vectors and
      duration of treatment whilst relevant patient factors are both biological and
      behavioural. Hence, the natural variation between orthodontic treatment plans and
      patients gives rise to variations in risk. A good understanding of these risks is
      required for clinicians to obtain informed consent before starting treatment as
      well as to reduce the potential for harm during treatment. After considering each
      of these risks, a conceptual framework is presented to help clinicians better
      understand how orthodontic risks arise and may therefore be mitigated.

PMID- 27868203
TI  - In response to Comparative study on the effects of EGF and bFGF on the healing of
      human large traumatic perforations of the tympanic membrane.

PMID- 27868204
TI  - Bioengineering pediatric scaffold-free auricular cartilaginous constructs.
AB  - OBJECTIVE: The use of exogenous materials as scaffolds in cartilage tissue
      engineering has limited the clinical application of resultant constructs due to
      the risk of postoperative complications. In an effort to minimize such
      complications, we aim to generate human, scaffold-free auricular cartilaginous
      constructs. STUDY DESIGN: Laboratory study using pediatric auricular cartilage.
      METHODS: Remnant, normal pediatric auricular cartilage samples that would have
      otherwise been discarded were collected and digested to free cells. Harvested
      cells were cultured and expanded in vitro for two passages and plated as
      micromass cultures. The culture medium was replaced with a chemically defined
      chondrogenic medium, and cellular monolayers surrounding micromass cultures were
      continuously scraped off. Constructs were allowed to mature for a period of 8
      weeks. RESULTS: Micromass constructs showed mechanical stability and structurally
      resembled native auricular tissue, with a perichondrium-like layer of cells
      surrounding the inner cartilaginous zone. Constructs accumulated equivalent
      sulphated glycosaminoglycan and 50% of collagen content compared to native
      auricular cartilage by mass, while displaying 156% more cellularity. CONCLUSIONS:
      High-density micromass cultures of pediatric auricular chondrocytes can generate
      stable cartilaginous constructs following prolonged chondrogenic inductions in
      vitro. This technique is an essential step toward the development of three
      dimensional constructs to recreate clinically applicable auricular cartilaginous
      constructs. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E153-E158, 2017.

PMID- 27868205
TI  - Antioxidant properties and global metabolite screening of the probiotic yeast
      Saccharomyces cerevisiae var. boulardii.
AB  - BACKGROUND: Saccharomyces cerevisiae var. boulardii is the only yeast species
      with probiotic properties. It is considered to have therapeutic significance in
      gastrointestinal disorders. In the present study, a comparative physiological
      study between this yeast and Saccharomyces cerevisiae (BY4742) was performed by
      evaluating two prominent traits of probiotic species, responses to different
      stress conditions and antioxidant capacity. A global metabolite profile was also
      developed aiming to identify which therapeutically important secondary
      metabolites are produced. RESULTS: Saccharomyces cerevisiae var. boulardii showed
      no significant difference in growth patterns but greater stress tolerance
      compared to S. cerevisiae. It also demonstrated a six- to 10-fold greater
      antioxidant potential (judged by the 1,1-diphenyl-2-picrylhydrazyl assay), with a
      70-fold higher total phenolic content and a 20-fold higher total flavonoid
      content in the extracellular fraction. These features were clearly differentiated
      by principal component analysis and further indicated by metabolite profiling.
      The extracellular fraction of the S. cerevisiae var. boulardii cultures was found
      to be rich in polyphenolic metabolites: vanillic acid, cinnamic acid, phenyl
      ethyl alcohol (rose oil), erythromycin, amphetamine and vitamin B6 , which
      results in the antioxidant capacity of this strain. CONCLUSION: The present study
      presents a new perspective for differentiating the two genetically related
      strains of yeast, S. cerevisiae and S. cerevisiae var. boulardii by assessing
      their metabolome fingerprints. In addition to the correlation of the phenotypic
      properties with the secretory metabolites of these two yeasts, the present study
      also emphasizes the potential to exploit S. cerevisiae var. boulardii in the
      industrial production of these metabolites. (c) 2016 Society of Chemical
      Industry.

PMID- 27868206
TI  - Impact of short sleep on metabolic variables in obese children with obstructive
      sleep apnea.
AB  - OBJECTIVES/HYPOTHESIS: To analyze the association between sleep duration,
      metabolic variables, and insulin resistance in obese children with and without
      obstructive sleep apnea. The decline in sleep duration has paralleled a dramatic
      increase in the prevalence of obesity and diabetes, suggesting a mechanistic
      relationship. STUDY DESIGN: Retrospective, case series. METHODS: Consecutive
      obese patients 3 to 12 years of age who underwent polysomnography (PSG) and a
      metabolic panel and who completed a 14-item sleep questionnaire were analyzed.
      All laboratory testing was conducted within 3 months of PSG. Total sleep times
      were obtained from the PSG and confirmed by the questionnaire. RESULTS: A total
      of 171 patients (55.0% male) were studied. All patients were obese (body mass
      index [BMI] z score > 95th percentile). Patients were categorized into three
      groups: short sleepers, borderline sleepers, and optimal sleepers. Eighty-six
      (50.3%) patients were short sleepers, 71 (41.5%) were borderline sleepers, and 14
      (8.2%) were optimal sleepers. The mean BMI z score was 3.13 +/- 1.3 in short
      sleepers, 3.3 +/- 1.1 in borderline sleepers, and 3.5 +/- 1.5 in optimal sleepers
      (P = .39). There was no statistical difference in high- and low-density
      lipoprotein levels (P = .21 and P = .76, respectively) and total cholesterol (P =
      .43) among subgroups. Triglycerides, blood glucose, insulin, and homeostasis
      model assessment-insulin resistance were significantly higher in short sleepers
      when compared to borderline or normal sleepers (P = .008, P < .001, P < .001, and
      P < .001, respectively). CONCLUSIONS: Short sleep duration was correlated with
      alterations in metabolic variables and insulin resistance in obese patients. This
      raises concern for development of comorbid conditions that can persist into
      adulthood. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:2176-2181, 2017.

PMID- 27868208
TI  - Special issue on lasers in dentistry.

PMID- 27868207
TI  - Extracorporeal Clearance of Levetiracetam During Continuous Venovenous
      Hemofiltration in a Critically Ill Patient and New Dosing Recommendation.

PMID- 27868209
TI  - Determination of lithium and transition metals in Li1 Ni1/3 Co1/3 Mn1/3 O2 (NCM)
      cathode material for lithium-ion batteries by capillary electrophoresis.
AB  - In this work, we present a novel electrophoretic method that was developed for
      the determination of lithium and transition metals in LiNi1/3 Co1/3 Mn1/3 O2
      cathode material after microwave digestion. The cations in the digested LiNi1/3
      Co1/3 Mn1/3 O2 material were separated by CE and the element content was
      determined by UV/Vis detection. To characterize the precision of the
      measurements, the RSDs and concentrations were calculated and compared to those
      obtained with ICP-optical emission spectrometry (ICP-OES). Furthermore, a
      certified reference material (BCR 176R-fly ash) was investigated for all
      techniques. For active material components, the LOD and LOQ were determined. The
      LODs and LOQs for the metals determined by CE were as follows: lithium (LOD/LOQ):
      17.41/62.70 MUg/L, cobalt (LOD/LOQ): 348.4/1283 MUg/L, manganese (LOD/LOQ):
      540.2/2095 MUg/L, and nickel (LOD/LOQ): 838.0/2982 MUg/L. Recovery rates for
      lithium were in the range of 95-103%. It could be proven that with the new
      technique, the results for the determination of the lithium content of active
      material were comparable with those obtained by ICP-OES and ion chromatography.
      Furthermore, the recovery rates of the transition metals were determined to be
      between 96 and 110% by CE and ICP-OES.

PMID- 27868211
TI  - Sound effects: Multimodal input helps infants find displaced objects.
AB  - Before 9 months, infants use sound to retrieve a stationary object hidden by
      darkness but not one hidden by occlusion, suggesting auditory input is more
      salient in the absence of visual input. This article addresses how audiovisual
      input affects 10-month-olds' search for displaced objects. In AB tasks, infants
      who previously retrieved an object at A subsequently fail to find it after it is
      displaced to B, especially following a delay between hiding and retrieval.
      Experiment 1 manipulated auditory input by keeping the hidden object audible
      versus silent, and visual input by presenting the delay in the light versus dark.
      Infants succeeded more at B with audible than silent objects and, unexpectedly,
      more after delays in the light than dark. Experiment 2 presented both the delay
      and search phases in darkness. The unexpected light-dark difference disappeared.
      Across experiments, the presence of auditory input helped infants find displaced
      objects, whereas the absence of visual input did not. Sound might help by
      strengthening object representation, reducing memory load, or focusing attention.
      This work provides new evidence on when bimodal input aids object processing,
      corroborates claims that audiovisual processing improves over the first year of
      life, and contributes to multisensory approaches to studying cognition. Statement
      of contribution What is already known on this subject Before 9 months, infants
      use sound to retrieve a stationary object hidden by darkness but not one hidden
      by occlusion. This suggests they find auditory input more salient in the absence
      of visual input in simple search tasks. After 9 months, infants' object
      processing appears more sensitive to multimodal (e.g., audiovisual) input. What
      does this study add? This study tested how audiovisual input affects 10-month
      olds' search for an object displaced in an AB task. Sound helped infants find
      displaced objects in both the presence and absence of visual input. Object
      processing becomes more sensitive to bimodal input as multisensory functions
      develop across the first year.

PMID- 27868210
TI  - Computing infrared spectra of proteins using the exciton model.
AB  - The ability to compute from first principles the infrared spectrum of a protein
      in solution phase representing a biological system would provide a useful
      connection to atomistic models of protein structure and dynamics. Indeed, such
      calculations are a vital complement to 2DIR experimental measurements, allowing
      the observed signals to be interpreted in terms of detailed structural and
      dynamical information. In this article, we have studied nine structurally and
      spectroscopically well-characterized proteins, representing a range of structural
      types. We have simulated the equilibrium conformational dynamics in an explicit
      point charge water model. Using the resulting trajectories based on MD
      simulations, we have computed the one and two dimensional infrared spectra in the
      Amide I region, using an exciton approach, in which a local mode basis of
      carbonyl stretches is considered. The role of solvent in shifting the Amide I
      band (by 30 to 50 cm-1 ) is clearly evident. Similarly, the conformational
      dynamics contribute to the broadening of peaks in the spectrum. The inhomogeneous
      broadening in both the 1D and 2D spectra reflects the significant conformational
      diversity observed in the simulations. Through the computed 2D cross-peak
      spectra, we show how different pulse schemes can provide additional information
      on the coupled vibrations. (c) 2016 The Authors. Journal of Computational
      Chemistry Published by Wiley Periodicals, Inc.

PMID- 27868213
TI  - Characteristics and Outcomes of Concurrently Diagnosed New Rapid Atrial
      Fibrillation or Flutter and New Reduced Ejection Fraction.
AB  - BACKGROUND: Characteristics and outcomes of concurrently diagnosed new rapid
      atrial fibrillation (AF) or atrial flutter (AFL) and new heart failure with
      reduced left ventricular ejection fraction (LVEF) are not well described.
      METHODS: A retrospective cohort study of subjects referred for expedited
      transesophageal echocardiography-guided rhythm-control strategies for concurrent
      new rapid AF/AFL and new LVEF <= 40% diagnosed during the same admission was
      analyzed. RESULTS: Twenty-five subjects (median age 57 years; 96% male; 96%
      Caucasian; median CHA2 DS2 -VASc = 2) presented with new AF (n = 18) or AFL (n =
      7) with rapid ventricular rate (median 135 beats/min) and new reduced LVEF
      (median 27%; range, 10-37.5%). Seven (28%) subjects had left atrial appendage
      thrombi (LAAT) and five (20%) subjects had heavy or binge alcohol use. Baseline
      characteristics were similar between those with and without LAAT. Thirteen
      subjects with AF and without LAAT underwent direct-current cardioversion (DCCV)
      and 10 (77%) had AF recurrence within 90 days. Improvement of long-term LVEF to
      >40% was comparable for subjects with and without initial LAAT (83% vs 94%; P =
      0.46). Three of four subjects who received primary prophylaxis implantable
      cardioverter-defibrillators improved their LVEF to >35% after sinus rhythm
      maintenance. The median long-term follow-up time was 3.0 years. CONCLUSIONS:
      Subjects with concurrently diagnosed new rapid AF/AFL and new reduced LVEF are
      characterized by a high prevalence of LAAT and significant alcohol use. AF
      subjects without initial LAAT who underwent DCCV had a high 90-day AF recurrence
      rate. The presence of LAAT did not have a prognosticative effect on eventual LVEF
      improvement, which was observed in almost all subjects.

PMID- 27868212
TI  - Myelodysplastic Syndromes and Acute Myeloid Leukemia After Radiotherapy for
      Prostate Cancer: A Population-Based Study.
AB  - BACKGROUND: To understand the impact of radiotherapy on the development of
      myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) among elderly
      prostate cancer patients. METHODS: We performed a retrospective cohort study of
      elderly prostate cancer patients diagnosed during 1999-2011 by using the National
      Cancer Institute's Surveillance, Epidemiology and End Results-Medicare linked
      database. Competing risk analyses adjusting for patient characteristics were
      conducted to assess the impact of radiotherapy on the development of subsequent
      MDS/AML, compared with surgery. RESULTS: Of 32,112 prostate cancer patients,
      14,672 underwent radiotherapy, and 17,440 received surgery only. The median
      follow-up was 4.68 years. A total of 157 (0.47%) prostate cancer patients
      developed subsequent MDS or AML, and the median time to develop MDS/AML was 3.30
      (range: 0.16-9.48) years. Compared with prostate cancer patients who received
      surgery only, patients who underwent radiotherapy had a significantly increased
      risk of developing MDS/AML (hazard ratio [HR] =1.51, 95% confidence interval
      [CI]: 1.07-2.13). When radiotherapy was further categorized by modalities
      (brachytherapy, conventional conformal radiotherapy, and intensity-modulated
      radiotherapy [IMRT]), increased risk of second MDS/AML was only observed in the
      IMRT group (HR = 1.66, 95% CI: 1.09-2.54). CONCLUSIONS: Our findings suggest that
      radiotherapy for prostate cancer increases the risk of MDS/AML, and the impact
      may differ by modality. Additional studies with longer follow-up are needed to
      further clarify the role of radiotherapy in the development of subsequent myeloid
      malignancies. A better understanding may help patients, physicians, and other
      stakeholders make more informed treatment decisions. Prostate 77:437-445, 2017.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27868214
TI  - Low Intratumoral Mast Cells Are Associated With a Higher Risk of Prostate Cancer
      Recurrence.
AB  - BACKGROUND: Mast cells are of interest in prostate cancer because they possess
      both pro- and anti-tumorigenic properties and are present in the tumor
      microenvironment. We studied the association of mast cell count and densities
      with prostate cancer recurrence using tissue microarrays (TMAs) for 462 men who
      recurred (cases) and 462 controls that were matched to the cases nested in a
      cohort of radical prostatectomy patients. METHODS: Dual-immunostaining for mast
      cell tryptase and epithelial cytokeratin-8 and whole slide image analysis were
      used to assess total mast cell number, mast cell density (mast cell number/tissue
      area), and mast cell number per epithelial or stromal area in TMA spots
      containing tumor (up to 4 per man). We used conditional logistic regression to
      estimate the odds ratio (OR) and 95% confidence interval of recurrence for the
      mean, minimum, and maximum mast cell parameters in tumor tissue among each man's
      TMA spots. RESULTS: After taking into account matching factors of age, race,
      Gleason sum, and pathologic stage, higher minimum mast cell density in the tumor
      (comparing highest to lowest quartiles: OR = 0.58, 95% CI 0.40-0.86; P-trend =
      0.004) was associated with a lower risk of recurrence. Patterns for mast cell
      number and ratio of mast cell number to epithelial or stromal area were similar
      to those for mast cell density. CONCLUSIONS: Our results suggest that
      intratumoral mast cells may be protective against prostate cancer recurrence and
      could potentially serve as a prognostic biomarker after prostatectomy. Prostate
      77: 412-424, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27868215
TI  - The contribution of clinical and psychosocial factors to fatigue in 182 patients
      with inflammatory bowel disease: a cross-sectional study.
AB  - BACKGROUND: Fatigue is a frequently reported and predominant symptom experienced
      by patients with inflammatory bowel disease (IBD) and its impact has been
      associated with poorer quality of life (QoL). The complex interplay between
      disease-related variables and potentially modifiable psychosocial factors in IBD
      fatigue has yet to be unravelled. AIM: To evaluate the contribution of clinical,
      sociodemographic and psychosocial factors to the severity and impact of IBD
      fatigue and QoL. METHOD: In a cross-sectional study, 182 patients with IBD were
      recruited from three tertiary referral hospitals' out-patient clinics in London.
      Fatigue was assessed utilising the Inflammatory Bowel Disease-Fatigue Scale (IBD
      F), the Multidimensional Fatigue Inventory (MFI); and QoL by the Inflammatory
      Bowel Disease Questionnaire (IBDQ). Patients completed self-report questionnaires
      evaluating emotional, cognitive and behavioural factors potentially correlated
      with fatigue. Sociodemographic data were collected. Disease-related and
      laboratory data were retrieved from patients' hospital electronic medical
      records. RESULT: In hierarchical regression models, disease activity was the only
      clinical factor consistently associated with severity and impact of fatigue and
      QoL (P = 0.01). More negative fatigue perceptions were significantly associated
      with greater IBD-F1 scores (P = 0.01). When controlling for clinical factors
      (disease activity and anti-TNF therapy), negative perceptions of fatigue, and all
      or-nothing and avoidance behaviours explained an additional 41% of the variance
      in fatigue impact (IBD-F2). CONCLUSIONS: Apart from disease activity, emotional
      and behavioural factors and patients' negative fatigue perceptions may be key
      factors to be addressed. Further exploration of these factors in longitudinal and
      intervention studies may help to develop effective models of fatigue management.

PMID- 27868217
TI  - Chronic opioid use is associated with altered gut microbiota and predicts
      readmissions in patients with cirrhosis.
AB  - BACKGROUND: Opioid use is epidemic in cirrhosis, which could precipitate hepatic
      encephalopathy (HE) potentially through gut dysbiosis and inflammation. AIM: To
      define the effect of opioids on readmissions and on gut microbiota composition
      and functionality. METHODS: Cohort 1 had 200 cirrhotic in-patients (with/without
      opioid use) followed prospectively through the index hospitalisation and 6 months
      post discharge. Readmissions (HE-related/unrelated) were compared between
      patients discharged on opioids compared to the rest, including using a multi
      variable analysis. Cohort 2 consisted of 72 cirrhotics on chronic opioids who
      were age/model for end-stage liver disease (MELD) and prior HE-balanced with 72
      cirrhotics not on opioids. Stool microbiota composition (multi-tagged
      sequencing), predicted functionality (PiCRUST), endotoxemia and systemic
      inflammation (IL-6, IL-17) were compared. RESULTS: Cohort 1: Chronic opioid use
      was statistically similar between those admitted with/without HE, and was judged
      to be an HE precipitant in <5% of cases during the index hospitalisation. Of the
      144 patients alive at 6 months, 82 were readmitted. The opioid users had a
      significantly higher all cause (69% vs. 48%, P = 0.008), but not HE-related
      readmissions (30% vs. 41%, P = 0.30). On regression, opioid therapy and female
      gender were predictive of readmission independent of MELD score and previous HE.
      Cohort 2: Significant dysbiosis was noted in the opioid cohort, especially in
      HE+opioid patients with lower autochthonous taxa and Bacteroidaceae relative
      abundance. PiCRUST showed highest aromatic amino acid and endotoxin production in
      opioid users. Opioid users also had higher endotoxemia and IL-6 but not IL-17.
      CONCLUSION: Chronic opioid use in cirrhosis is associated with increased
      endotoxemia, dysbiosis and all-cause readmissions.

PMID- 27868218
TI  - Simultaneous determination of l-tetrahydropalmatine and its active metabolites in
      rat plasma by a sensitive ultra-high-performance liquid chromatography with
      tandem mass spectrometry method and its application in a pharmacokinetic study.
AB  - A sensitive and reliable ultra-high-performance liquid chromatography with tandem
      mass spectrometry (UHPLC-MS/MS) method was developed and validated for
      simultaneous determination of l-tetrahydropalmatine (l-THP) and its active
      metabolites l-isocorypalmine (l-ICP) and L-corydalmine (l-CD) in rat plasma. The
      analytes were extracted by liquid-liquid extraction and separated on a Bonshell
      ASB C18 column (2.1 * 100 mm; 2.7 MUm; Agela) using acetonitrile-formic acid
      aqueous as mobile phase at a flow rate of 0.2 mL/min in gradient mode. The method
      was validated over the concentration range of 4.00-2500 ng/mL for l-THP, 0.400
      250 ng/mL for l-ICP and 1.00-625 ng/mL for l-CD. Intra- and inter-day accuracy
      and precision were within the acceptable limits of <15% at all concentrations.
      Correlation coefficients (r) for the calibration curves were >0.99 for all
      analytes. The quantitative method was successfully applied for simultaneous
      determination of l-THP and its active metabolites in a pharmacokinetic study
      after oral administration with l-THP at a dose of 15 mg/kg to rats.

PMID- 27868216
TI  - The Endoscopic Reference Score shows modest accuracy to predict either clinical
      or histological activity in adult patients with eosinophilic oesophagitis.
AB  - BACKGROUND: Conflicting results have been recently reported for the accuracy of
      the Endoscopic Reference Score (EREFS), an standardised endoscopic
      classification, to predict the histological activity of eosinophilic oesophagitis
      (EoE). AIM: To evaluate the accuracy of the EREFS to predict either histological
      or clinical activity of EoE. METHODS: Prospective multicentre study conducted in
      eight Spanish centres evaluating adult EoE patients, either naive or after
      treatment. Symptoms were evaluated before upper endoscopy through the Dysphagia
      Symptom Score, whereas researchers scored the EREFS immediately after the
      endoscopic procedure, unaware of the histological outcome. RESULTS: One hundred
      and forty-five EoE patients undergoing 240 consecutive endoscopic procedures were
      included. Exudates (P = 0.03), furrows (P = 0.03) and a composite score of
      inflammatory signs (exudates, furrows and oedema) (P < 0.001) accurately
      predicted histological activity. Exudates were the only endoscopic sign showing a
      good correlation with histological outcome after therapy. Furrows and oedema
      persisted in 50% and 70% of patients despite histological remission. No
      endoscopic feature exceeded 70% accuracy to predict histological activity.
      Likewise, no endoscopic finding could adequately predict dysphagia severity.
      Crepe paper mucosa, diffuse exudates and severe rings correlated with higher
      symptom scores. CONCLUSIONS: Endoscopic findings assessed by the Endoscopic
      Reference Score did not correlate with histological or clinical disease activity
      in adult EoE patients. Only exudates correlated with peak eosinophil count and
      histological outcome, whereas furrows and oedema persisted in over half of
      patients despite histological remission.

PMID- 27868219
TI  - New Heart...New Rhythm.

PMID- 27868220
TI  - Steady-state protein focusing in carrier ampholyte-based isoelectric focusing:
      Part II-validation and case studies.
AB  - In this study, we systematically investigate the validity and applicability of an
      analytical model developed for carrier ampholyte-based isoelectric focusing
      (IEF). Three different IEF cases are considered in order to evaluate the efficacy
      of the approximate analytical results by comparison with high-resolution computer
      simulations. In the first case, three proteins are separated in a narrow pH range
      (6-9) by using 50 carrier ampholytes. In the second and third cases, the
      separation of proteins is studied in broad pH range (3-10) IEF by using 100
      carrier ampholytes. Results obtained from the approximate analytical models are
      in very good agreement with the numerical results for IEF separation of cardiac
      troponin I, albumin, and hemoglobin in both narrow and broad pH ranges. The
      sensitivity of the analytical model is also tested for different initial mass
      ratios of proteins to ampholytes. No appreciable differences are observed between
      the approximate analytical and numerical results within the mass ratio range
      studied. The effect of a nominal electric field and/or a nominal pH gradient on
      protein focusing is also examined to demonstrate the effectiveness of the
      analytical model. Our results indicate that the use of both nominal electric
      field and pH gradient will result in erroneous peak concentrations for proteins.
      Finally, we describe the limitations of the approximate analytical solutions.

PMID- 27868222
TI  - Adaptive partitioning by local density-peaks: An efficient density-based
      clustering algorithm for analyzing molecular dynamics trajectories.
AB  - We present an efficient density-based adaptive-resolution clustering method APLoD
      for analyzing large-scale molecular dynamics (MD) trajectories. APLoD performs
      the k-nearest-neighbors search to estimate the density of MD conformations in a
      local fashion, which can group MD conformations in the same high-density region
      into a cluster. APLoD greatly improves the popular density peaks algorithm by
      reducing the running time and the memory usage by 2-3 orders of magnitude for
      systems ranging from alanine dipeptide to a 370-residue Maltose-binding protein.
      In addition, we demonstrate that APLoD can produce clusters with various sizes
      that are adaptive to the underlying density (i.e., larger clusters at low-density
      regions, while smaller clusters at high-density regions), which is a clear
      advantage over other popular clustering algorithms including k-centers and k
      medoids. We anticipate that APLoD can be widely applied to split ultra-large MD
      datasets containing millions of conformations for subsequent construction of
      Markov State Models. (c) 2016 Wiley Periodicals, Inc.

PMID- 27868221
TI  - What's new in atopic eczema? An analysis of systematic reviews published in 2014.
      Part 2. Treatment and prevention.
AB  - This review forms part of a series of annual updates that summarize the evidence
      base for atopic eczema (AE). It provides a summary of key findings from 12
      systematic reviews (SRs) that were published or indexed during 2014, and focuses
      on the treatment and prevention of AE. For an update of SRs on the epidemiology,
      mechanisms of disease and methodological issues, see Part 1 of this update.
      Although phototherapy and various systemic medications (including ciclosporin,
      azathioprine and methotrexate) are commonly used to treat AE, many of these have
      not been robustly assessed in head-to-head randomized controlled trials.
      Educational interventions may improve AE severity and quality of life for
      children and their families. Intake of probiotics prenatally and postnatally may
      help prevent AE, but there is little evidence to suggest a role in the treatment
      of AE. Although no benefit was found for allergen avoidance in preventing AE, the
      use of immunotherapy to treat AE-associated aeroallergen sensitivity requires
      further evaluation. There is insufficient evidence for Vitamin D supplementation
      for the treatment of AE This overview of reviews provides a succinct guide for
      clinicians and patients wishing to remain up to date with the most recent
      evidence for the treatment and prevention of AE.

PMID- 27868223
TI  - Synthesis of unlabelled and stable-isotope-labelled glucuronide metabolites of
      dapagliflozin and synthesis of stable-isotope-labelled dapagliflozin.
AB  - Two regioisomeric glucuronide metabolites of dapagliflozin (BMS-512148) were
      synthesized and used to elucidate the structures of dapagliflozin metabolites
      observed in human urine samples. The structures of the synthetic metabolites were
      assigned by heteronuclear multiple-bond correlation, ROESY, and total correlation
      spectroscopy experiments. Analogues of these metabolites containing carbon-13 as
      a stable label were also prepared for use as internal standards for the analysis
      of urine samples obtained from patients participating in clinical studies.

PMID- 27868224
TI  - Evaluation of levator ani muscle throughout the different stages of labor by
      transperineal 3D ultrasound.
AB  - OBJECTIVE: Description and assessment by 3-D transperineal ultrasound of
      modifications suffered by pelvic floor muscles during the passage of the fetal
      head through the birth canal during the second stage of labor, as well as the
      identification of the precise moment in which levator ani muscle avulsion takes
      place. MATERIALS AND METHODS: Patients included were 35 primigravidae, recruited
      during the first stage of labor, with at term pregnancy (37-42 weeks), without
      serious maternal-fetal pathology and cephalic presentation. A prospective
      observational study of 35 primigravidae, recruited during the first stage of
      labor, with at term pregnancy (37-42 weeks), with fetus in cephalic presentation
      and without serious maternal-fetal pathology. Sonographic evaluation was carried
      out by 3-D transperineal ultrasound during the first and second stages of labor
      (with fetal head in 1st, 2nd-3rd and 4th planes of Hodge), immediately postpartum
      and 6 months postpartum. Ultrasound parameters studied were antero-posterior and
      transverse diameters, as well as levator hiatus area and levator ani muscle
      thickness and area. RESULTS: Twenty-one patients were studied (15 spontaneous
      deliveries; 6 instrumental deliveries). When measured with fetal head in the 4th
      plane of Hodge, a significant increase both in the levator hiatus area (15.39 cm2
      /15.68 cm2 /20.96 cm2 /42.55 cm2 /22.92 cm2 /18.18 cm2 ; P < 0.0005) and in the
      levator ani muscle area (8.78 cm2 /9.18 cm2 /9.69 cm2 /15.07 cm2 /11.33 cm2
      /12.36 cm2 ; P < 0.0005) was identified. Four cases of unilateral right avulsion
      (two vacuum and two forceps deliveries) were identified. CONCLUSIONS: We conclude
      that the phase of delivery that causes a major increase in the area of the
      levator hiatus area and in the levator ani muscle area is when the fetal head
      reaches the 4th plane of Hodge. Furthermore, data in our paper indicates that the
      exact moment in which the avulsion of the levator ani muscle is produced is when
      the bulging of the fetal head on the maternal perineum occurs.

PMID- 27868226
TI  - Factors affecting patient reporting of adverse drug reactions: a systematic
      review.
AB  - AIM: The aim of the present study was to determine the barriers and motives
      influencing consumer reporting of adverse drug reactions (ADRs). METHODS: A
      systematic review, guided by the Cochrane Handbook, was conducted. Electronic
      searches included MEDLINE, EMBASE, PsycINFO, CINAHL, PubMed and the Cochrane
      Database of Systematic Reviews from 1964 to December 2014. Eligible studies
      addressed patients' perceptions and factors influencing ADR reporting. Studies
      about healthcare professional (HCP) reporting of ADRs were excluded. Studies were
      appraised for quality, and results were analysed descriptively. RESULTS: Of 1435
      citations identified, 21 studies were eligible. Studies were primarily conducted
      in the UK, the Netherlands and Australia. The identified barriers to patient
      reporting of ADRs (n = 15 studies) included poor awareness, confusion about who
      should report the ADR, difficulties with reporting procedures, lack of feedback
      on submitted reports, mailing costs, ADRs resolved and prior negative reporting
      experiences. The identified motives for patients reporting ADRs (n = 10 studies)
      were: preventing others from having similar ADRs, wanting personal feedback,
      improving medication safety, informing regulatory agencies, improving HCP
      practices, responding to HCPs not reporting their ADRs and having been asked to
      report ADRs by HCPs. CONCLUSIONS: Most patients were not aware of reporting
      systems and others were confused about reporting. Patients were mainly motivated
      to make their ADRs known to prevent similar suffering in other patients. By
      increasing patient familiarity and providing clear reporting processes, reporting
      systems could better achieve patient reporting of ADRs.

PMID- 27868227
TI  - Associated factors of behavioural problems in children at preschool age: the
      Hokkaido study on environment and children's health.
AB  - BACKGROUND: Finding associated factors with childhood behavioural problems as
      early as preschool age is important. Studies have revealed several factors
      including socioeconomic factors, which may vary among different cultural
      background and population. However, investigation in general Japanese population
      of preschool age has not been well demonstrated. Thus, the objective of this
      study was to examine associated factors of childhood behavioural problems using
      Strengths and Difficulties Questionnaire (SDQ) in a prospective birth cohort
      study. METHODS: Total 3813 SDQ were distributed between October 2014 and December
      2015 to the subpopulation of prospective birth cohort study, the Hokkaido Study
      on Environment and Children's Health. The subpopulation consisted of participants
      who had reached age 5 and were born between April 2008 and December 2010.
      Baseline questionnaire filled at recruitment and birth record were used to obtain
      participant information. Children with total difficulties score ? 13 were defined
      as likelihood of behavioural problems. A total of 2553 children with valid
      answers were included into the analysis. The response rate was 67.1%. RESULTS:
      Number of children with likelihood of behavioural problems was 521 (20.4%). Boys
      showed more problematic scores than girls. Multivariate analysis found that
      maternal pre-pregnancy BMI ? 30 kg/m2 , primipara, maternal education lower than
      high school, family income during pregnancy < 3 million yen/year and boy gender
      were the factors associated with increased odds ratio of likelihood of child
      behavioural problems. CONCLUSIONS: This study found that prenatal socioeconomic
      factors were associated with likelihood of child behavioural problems at
      preschool age in Japan.

PMID- 27868225
TI  - First Language Attrition Induces Changes in Online Morphosyntactic Processing and
      Re-Analysis: An ERP Study of Number Agreement in Complex Italian Sentences.
AB  - First language (L1) attrition in adulthood offers new insight on neuroplasticity
      and the role of language experience in shaping neurocognitive responses to
      language. Attriters are multilinguals for whom advancing L2 proficiency comes at
      the cost of the L1, as they experience a shift in exposure and dominance (e.g.,
      due to immigration). To date, the neurocognitive mechanisms underlying L1
      attrition are largely unexplored. Using event-related potentials (ERPs), we
      examined L1-Italian grammatical processing in 24 attriters and 30 Italian native
      controls. We assessed whether (a) attriters differed from non-attriting native
      speakers in their online detection and re-analysis/repair of number agreement
      violations, and whether (b) differences in processing were modulated by L1
      proficiency. To test both local and non-local agreement violations, we
      manipulated agreement between three inflected constituents and examined ERP
      responses on two of these (subject, verb, modifier). Our findings revealed group
      differences in amplitude, scalp distribution, and duration of LAN/N400 + P600
      effects. We discuss these differences as reflecting influence of attriters' L2
      English, as well as shallower online sentence repair processes than in non
      attriting native speakers. ERP responses were also predicted by L1-Italian
      proficiency scores, with smaller N400/P600 amplitudes in lower proficiency
      individuals. Proficiency only modulated P600 amplitude between 650 and 900 ms,
      whereas the late P600 (beyond 900 ms) depended on group membership and amount of
      L1 exposure within attriters. Our study is the first to show qualitative and
      quantitative differences in ERP responses in attriters compared to non-attriting
      native speakers. Our results also emphasize that proficiency predicts language
      processing profiles, even in native-speakers, and that the P600 should not be
      considered a monolithic component.

PMID- 27868229
TI  - The synthesis of a tritium, carbon-14, and stable isotope-labeled cathepsin C
      inhibitors.
AB  - As part of a medicinal chemistry program aimed at developing a highly potent and
      selective cathepsin C inhibitor, tritium, carbon-14, and stable isotope-labeled
      materials were required. The synthesis of tritium-labeled methanesulfonate 5 was
      achieved via catalytic tritiolysis of a chloro precursor, albeit at a low
      radiochemical purity of 67%. Tritium-labeled AZD5248 was prepared via a 3-stage
      synthesis, utilizing amide-directed hydrogen isotope exchange. Carbon-14 and
      stable isotope-labeled AZD5248 were successfully prepared through modifications
      of the medicinal chemistry synthetic route, enabling the use of available labeled
      intermediates.

PMID- 27868228
TI  - Pharmacokinetic interaction between taxanes and amiodarone leading to severe
      toxicity.
AB  - ADVERSE EVENT: A drug interaction leading to severe skin and mucosal toxicity.
      DRUGS IMPLICATED: Paclitaxel, docetaxel and amiodarone. THE PATIENT: A 77-year
      old woman with a history of hypertension, hyperlipidemia, and palpitations,
      managed with amiodarone, was treated for HER2-positive invasive ductal breast
      cancer with paclitaxel and trastuzumab as an adjunct to surgery. EVIDENCE THAT
      LINKS THE DRUG TO THE EVENT: There was a strong temporal relationship between the
      taxane therapy and the development of severe skin and mucosal toxicity due to an
      unexpected reduction in taxane clearance. MANAGEMENT: Initially, conversion of
      paclitaxel to docetaxel, then cessation of docetaxel, symptomatic treatment,
      rehydration and placement of a nasogastric tube. MECHANISM: Increased exposure to
      paclitaxel and subsequently docetaxel due to interaction with amiodarone was
      suspected and confirmed on pharmacokinetic sampling. Analysis of two blood
      samples taken 9 and 10 days after docetaxel revealed plasma levels of 4.73 and
      4.09 ng ml-1 , respectively, leading to a 79% decreased individual (Bayesian
      maximum a posteriori) clearance estimate of 9.15 l h-1 , corresponding to an
      estimated fivefold increase in AUC. Paclitaxel was also present in these samples
      (20 and 21 days after the last administration). IMPLICATIONS FOR THERAPY:
      Amiodarone inhibits cytochrome P450 (CYP) isoforms 2C8 and 3A4 as well as P
      glycoprotein (P-gp) for which taxanes are substrates. However, interactions with
      amiodarone are not specified in the prescribing information. Clinicians should be
      aware of this interaction, particularly in an ageing population, where more
      patients requiring taxanes may already be receiving amiodarone for a comorbid
      cardiac condition.

PMID- 27868230
TI  - No immediate effect on urodynamic parameters during transcutaneous electrical
      nerve stimulation (TENS) in children with overactive bladder and daytime
      incontinence-A randomized, double-blind, placebo-controlled study.
AB  - AIM: To evaluate the immediate effect on natural fill urodynamic parameters and
      bladder function during transcutaneous electrical nerve stimulation (TENS) in
      children with overactive bladder (OAB) and daytime urinary incontinence (DUI).
      MEETHODS: In this double-blind, placebo-controlled study, 24 children with severe
      OAB and DUI (mean age 8.5 +/- 1.2 years) underwent 48-h natural fill urodynamics.
      After 24 h of baseline investigation, the children were randomized to either
      active continuous TENS (n = 12) or placebo TENS (n = 12) over the sacral S2-S3
      outflow. The urodynamic recordings were analyzed manually for three different
      bladder contraction patterns resulting in a void. The number of bladder
      contractions not leading to a void was also calculated. Maximum voided volume
      (MVV) and average voided volume (AVV) were identified for both the baseline and
      the intervention day. RESULTS: We found that TENS had no immediate objective
      effect on bladder capacity. The difference (before minus after treatment) in
      MVV/EBC in the active TENS group = 0.03 +/- 0.23 versus placebo TENS group = 
      0.01 +/- 0.10 (P = 0.61). Also, there was no significant difference in the
      proportion of different bladder contraction types between the two groups. TENS
      did not significantly influence the number of bladder contractions not leading to
      a void. Results are presented as mean +/- SD. CONCLUSION: There is no immediate
      objective effect of TENS on bladder activity assessed by natural fill urodynamics
      in children with OAB and DUI.

PMID- 27868232
TI  - Prospective longitudinal associations between household smoke exposure in early
      childhood and antisocial behavior at age 12.
AB  - Young children exert little control over household tobacco smoke exposure, which
      is considered a developmental neurotoxicant. Using the Quebec Longitudinal Study
      birth cohort, we examine prospective associations between early childhood smoke
      exposure and later antisocial behavior. Parents of 1035 children reported on the
      presence of household smokers at seven follow-ups from ages 1.5 to 7.5. At age
      12, children self-reported on five aspects of early antisocial dispositions.
      After adjusting for confounders, every standard deviation increase in household
      smoke exposure was prospectively associated with a 19% standard deviation unit
      increase in conduct problems (beta=0.07; 95% confidence interval [CI] from 0.04
      to 0.09), a 11% standard deviation unit increase in proactive aggression
      (beta=0.04; 95% CI from 0.01 to 0.07), a 13% standard deviation unit increase in
      reactive aggression (beta=0.07; 95% CI from 0.03 to 0.12), a 14% standard
      deviation unit increase in school indiscipline (beta=0.13; 95% CI from 0.05 to
      0.20), and a 10% standard deviation unit increase in dropout risk (beta=0.07; 95%
      CI from 0.01 to 0.12). These long-term findings warrant fostering parental
      awareness of developmental risks by policy-makers/health practitioners. School
      curricula can equally integrate these ideas into their curriculum.

PMID- 27868233
TI  - Age-related changes in dermal fiber-like structures in facial cheeks.
AB  - BACKGROUND/PURPOSE: Despite recent progress in non-invasive measurement methods,
      such as in vivo laser confocal microscopy (CLSM), it is difficult to
      quantitatively measure age-related changes in dermal fibrous structures in the
      face using these methods and qualitative characteristics. We used characteristics
      extracted from the analysis of CLSM images to quantitatively investigate the
      effects of aging on dermal fibrous structures in the face. METHODS: CLSM images
      of dermal fibrous structures were obtained from 90 Japanese females, ranging in
      age from 20 to 60 years. The feature values of CLSM images were extracted using
      image analysis methods, such as short-line segment-matching processing and
      spatial frequency analysis. The qualitative characteristics of the dermal fibrous
      structures in the CLSM images were obtained by principal component analysis (PCA)
      of these feature values. The fibrous structures were scored on the basis of
      qualitative characteristics and then age-related changes in the scores among the
      subjects were quantitatively evaluated. RESULTS AND CONCLUSION: The PCA results
      showed that there were two characteristics in the images of fibrous structures:
      clearness and directionality. The clearness of fibrous structures decreased and
      directionality isotropy increased with age.

PMID- 27868231
TI  - Aprepitant in pediatric patients using moderate and highly emetogenic protocols:
      a systematic review and meta-analyses of randomized controlled trials.
AB  - AIMS: To review the efficacy and safety of aprepitant in combination with
      ondansetron and dexamethasone (triple therapy) in children and adolescents on
      moderate to highly emetogenic chemotherapy. METHODS: Medline, Embase, Scielo,
      Lilacs, Cochrane and congress abstracts published until September 2016 were used
      as data sources. Two reviewers independently selected manuscripts and extracted
      data. A third reviewer solved discrepancies in study selection and data
      extraction. The primary outcome was overall complete response (no vomiting from 0
      to 120 h). Secondary outcomes were: response in acute phase, delayed phase and
      reported toxicities. Each study was considered a unit of analysis. Summarized
      relative risks were recalculated based on reported data. All meta-analyses used a
      random-effects model and heterogeneity was reported using the I2 method. RESULTS:
      From 1004 studies, we screened 288 titles and abstracts and included three trials
      for data extraction. The population comprised 451 patients. Most patients were
      males, ranging from 6 months to 19 years of age, and weighing from 6 to 134 kg.
      Bone cancer was the most incident (>=50%) neoplasm, followed by rhabdomyosarcoma
      and Hodgkin's lymphoma. Triple therapy was associated with a reduced risk of
      developing chemotherapy-induced vomiting (CIV) (RR = 0.48; 95% CI 0.34-0.67).
      There were no differences in incidence of febrile neutropenia between groups (RR
      = 1.02; 95% CI 0.66-1.58). CONCLUSIONS: Triple therapy decreased CIV risk,
      without increasing the occurrence of febrile neutropenia. However, this review
      could not address which subpopulations would most benefit from using this
      strategy. Future studies should focus on assessing risk factors for nausea and
      vomiting, as many patients did not achieve a complete antiemetic response.

PMID- 27868235
TI  - Trait space of rare plants in a fire-dependent ecosystem.
AB  - The causes of species rarity are of critical concern because of the high
      extinction risk associated with rarity. Studies examining individual rare species
      have limited generality, whereas trait-based approaches offer a means to identify
      functional causes of rarity that can be applied to communities with disparate
      species pools. Differences in functional traits between rare and common species
      may be indicative of the functional causes of species rarity and may therefore be
      useful in crafting species conservation strategies. However, there is a
      conspicuous lack of studies comparing the functional traits of rare species and
      co-occurring common species. We measured 18 important functional traits for 19
      rare and 134 common understory plant species from North Carolina's Sandhills
      region and compared their trait distributions to determine whether there are
      significant functional differences that may explain species rarity. Flowering,
      fire, and tissue-chemistry traits differed significantly between rare and common,
      co-occurring species. Differences in specific traits suggest that fire
      suppression has driven rarity in this system and that changes to the timing and
      severity of prescribed fire may improve conservation success. Our method provides
      a useful tool to prioritize conservation efforts in other systems based on the
      likelihood that rare species are functionally capable of persisting.

PMID- 27868236
TI  - National continuous surveys on internal quality control for HbA1c in 306 clinical
      laboratories of China from 2012 to 2016: Continual improvement.
AB  - BACKGROUND: This study aimed to evaluate whether the quality performance of
      clinical laboratories in China has been greatly improved and whether Internal
      Quality Control (IQC) practice of HbA1c has also been changed since National
      Center for Clinical Laboratories (NCCL) of China organized laboratories to report
      IQC data for HbA1c in 2012. METHODS: Internal Quality Control information of 306
      External Quality Assessment (EQA) participant laboratories which kept reporting
      IQC data in February from 2012 to 2016 were collected by Web-based EQA system.
      Then percentages of laboratories meeting four different imprecision
      specifications for current coefficient of variations (CVs) of HbA1c measurements
      were calculated. Finally, we comprehensively analyzed analytical systems and IQC
      practice of HbA1c measurements. RESULTS: The current CVs of HbA1c tests have
      decreased significantly from 2012 to 2016. And percentages of laboratories
      meeting four imprecision specifications for CVs all showed the increasing
      tendency year by year. As for analytical system, 52.1% (159/306) laboratories
      changed their systems with the change in principle of assay. And many
      laboratories began to use cation exchange high-performance liquid chromatography
      (CE-HPLC) instead of Immunoturbidimetry, because CE-HPLC owed a lower intra
      laboratory CVs. The data of IQC practice, such as IQC rules and frequency, also
      showed significant variability among years with overall tendency of meeting
      requirements. CONCLUSION: The imprecision performance of HbA1c tests has been
      improved in these 5 years with the change in IQC practice, but it is still
      disappointing in China. Therefore, laboratories should actively find existing
      problems and take action to promote performance of HbA1c measurements.

PMID- 27868234
TI  - Efficient 31 P band inversion transfer approach for measuring creatine kinase
      activity, ATP synthesis, and molecular dynamics in the human brain at 7 T.
AB  - PURPOSE: To develop an efficient 31 P magnetic resonance spectroscopy (MRS)
      method for measuring creatine kinase (CK) activity, adenosine triphosphate (ATP)
      synthesis, and motion dynamics in the human brain at 7 Tesla (T). METHODS: Three
      band inversion modules differing in center frequency were used to induce
      magnetization transfer (MT) effect in three exchange pathways: (i) CK-mediated
      reaction PCr -> gamma-ATP; (ii) de novo ATP synthesis Pi -> gamma-ATP; and (iii)
      ATP intramolecular 31 P-31 P cross-relaxation gamma-(alpha-) <-> beta-ATP. The
      resultant MT data were analyzed using a 5-pool model in the format of
      magnetization matrix according to Bloch-McConnell-Solomon formalism. RESULTS:
      With a repetition time (TR) of 4 s, the scan time for each module was
      approximately 8 min. The rate constants were kPCr -> gammaATP 0.38 +/- 0.02 s-1 ,
      kPi -> gammaATP 0.19 +/- 0.02 s-1 , and sigmagamma(alpha) <-> betaATP 0.19 +/-
      0.04 s-1 , corresponding to ATP rotation correlation time tauc (0.8 +/- 0.2) .10
      7 s. The T1 relaxation times were Pi 7.26 +/- 1.76 s, PCr 5.99 +/- 0.58 s, gamma
      ATP 0.98 +/- 0.07 s, alpha-ATP 0.95 +/- 0.04 s, and beta-ATP 0.68 +/- 0.03 s.
      CONCLUSION: Short-TR band inversion modules provide a time-efficient way of
      measuring brain ATP metabolism and could be useful in studying metabolic
      disorders in brain diseases. Magn Reson Med 78:1657-1666, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27868237
TI  - Selenium-enriched Saccharomyces cerevisiae improves growth, antioxidant status
      and selenoprotein gene expression in Arbor Acres broilers.
AB  - One hundred and fifty 7-day-old Arbor Acres broilers were randomly assigned into
      five groups: group 1 served as a control that was fed a basal diet without
      selenium (Se) supplementation; groups 2, 3 and 4 were fed the basal diet
      supplemented with 0.15, 0.5 and 1.5 mg Se as Se-enriched Saccharomyces cerevisiae
      (SSC) per kg of diet; and group 5 was fed the basal diet supplemented with 0.15
      mg per kg of Se as sodium selenite (SS). Growth performance, glutathione
      peroxidase (GPX ) and superoxide dismutase (SOD) activities, total antioxidant
      capacity (T-AOC), and malondialdehyde (MDA) content in plasma and liver, and
      cellular glutathione peroxidase (GPX -1) and phospholipid hydroperoxide
      glutathione peroxidase (GPX -4) mRNA levels in liver were determined. Compared
      with group 1, groups 2-4 exhibited higher body weights (p < 0.05), lower
      feed/gain ratios, and higher GPX activities in plasma (p < 0.05) and GPX and SOD
      activities and GPX -1 and GPX -4 mRNA levels in liver (p < 0.05). Compared with
      group 5, group 2 exhibited higher GPX activity in plasma on day 21 (p < 0.05).
      Compared with group 2 and 5, group 3 exhibited lower MDA content in plasma on day
      7 (p < 0.05), higher GPX activity in plasma, SOD activity and GPX -1 mRNA levels
      in liver on day 14 and 21 (p < 0.05), and higher GPX -4 mRNA levels on day 14 (p
      < 0.05). Compared with group 4, group 3 exhibited lower MDA contents in plasma on
      day 14 (p < 0.05) and in liver on day 21 (p < 0.05), higher T-AOC in plasma and
      higher GPX -1 mRNA levels on day 14 and 21 (p < 0.05), and higher SOD activity in
      plasma and higher SOD and GPX activities in liver on day 21 (p < 0.05). Thus, SSC
      improves growth and antioxidant status of broilers; the short-term
      bioavailability of SS was faster than that of SSC, but the long-term
      bioavailability of SSC was greater than SS.

PMID- 27868238
TI  - Suppression of ghost artifacts arising from long T1 species in segmented
      inversion-recovery imaging.
AB  - PURPOSE: We demonstrate an improved segmented inversion-recovery sequence that
      suppresses ghost artifacts arising from tissues with long T1 ( > 1.5 s). THEORY
      AND METHODS: Long T1 species such as pericardial fluid can create bright ghost
      artifacts in segmented, inversion-recovery MRI because of oscillations in
      longitudinal magnetization between segments. A single dummy acquisition at the
      beginning of the sequence can reduce oscillations; however, its effectiveness in
      suppressing long T1 artifacts is unknown. In this study, we systematically
      evaluated several test sequences, including a prototype (saturation post-pulse
      readout to eliminate spurious signal: SPPRESS) in simulations, phantoms, and
      patients. RESULTS: SPPRESS reduced artifact signal 90% +/- 25% and 74% +/- 28%
      compared with Control and Single-Dummy methods in phantoms. SPPRESS performed
      well at 1.5 Tesla (T) and 3T, with steady-state free precession (SSFP) and fast
      low-angle shot (FLASH) readout, with conventional and phase-sensitive
      reconstruction, and over a range of physiologic heart rates. A review of 100
      consecutive clinical cardiac MRI scans revealed large fluid collections (eg,
      regions with long T1 ) in 14% of patients. In a prospectively enrolled cohort of
      16 patients with visible long T1 fluids, SPPRESS appreciably reduced artifacts in
      all cases compared with Control and Single-Dummy methods. CONCLUSION: We
      developed and validated a new robust method, SPPRESS, for reducing artifacts due
      to long T1 species across a wide range of imaging and physiologic conditions.
      Magn Reson Med 78:1442-1451, 2017. (c) 2016 International Society for Magnetic
      Resonance in Medicine.

PMID- 27868239
TI  - Co-exposure to sunlight enhances the toxicity of naturally weathered Deepwater
      Horizon oil to early lifestage red drum (Sciaenops ocellatus) and speckled
      seatrout (Cynoscion nebulosus).
AB  - The 2010 Deepwater Horizon oil spill resulted in the accidental release of
      millions of barrels of crude oil into the Gulf of Mexico. Photo-induced toxicity
      following co-exposure to ultraviolet (UV) radiation is 1 mechanism by which
      polycyclic aromatic hydrocarbons (PAHs) from oil spills may exert toxicity. Red
      drum and speckled seatrout are both important fishery resources in the Gulf of
      Mexico. They spawn near-shore and produce positively buoyant embryos that hatch
      into larvae in approximately 24 h. The goal of the present study was to determine
      whether exposure to UV as natural sunlight enhances the toxicity of crude oil to
      early lifestage red drum and speckled seatrout. Larval fish were exposed to
      several dilutions of high-energy water-accommodated fractions (HEWAFs) from 2
      different oils collected in the field under chain of custody during the 2010
      spill and 3 gradations of natural sunlight in a factorial design. Co-exposure to
      natural sunlight and oil significantly reduced larval survival compared with
      exposure to oil alone. Although both species were sensitive at PAH concentrations
      reported during the Deepwater Horizon spill, speckled seatrout demonstrated a
      greater sensitivity to photo-induced toxicity than red drum. These data
      demonstrate that even advanced weathering of slicks does not ameliorate the
      potential for photo-induced toxicity of oil to these species. Environ Toxicol
      Chem 2017;36:780-785. (c) 2016 SETAC.

PMID- 27868240
TI  - Omalizumab use during pregnancy for chronic spontaneous urticaria (CSU): report
      of two cases.

PMID- 27868241
TI  - High-intensity focused ultrasound treatment for skin: ex vivo evaluation.
AB  - BACKGROUND/PURPOSE: High-intensity focused ultrasound (HIFU) has been used for
      skin tightening. However, there is a rising concern of irreversible adverse
      effects. Our aim was to evaluate the depth of thermal injury zone after HIFU
      energy passes through different condition. MATERIALS AND METHODS: To analyze the
      consistency of the HIFU device, phantom tests were performed. Simulations were
      performed on ex vivo porcine tissues to estimate the area of the thermal
      coagulation point (TCP) according to the applied energy and skin condition. The
      experiment was designed in three orientations: normal direction (from epidermis
      to fascia), reverse direction (from fascia to epidermis), and normal direction
      without epidermis. RESULTS: The TCP was larger and wider depending on the applied
      fluence and handpieces (HPs). When we measured TCP in different directions, the
      measured area in the normal direction was more superficially located than that in
      the reverse direction. The depth of the TCP in the porcine skin without epidermis
      was detected at 130% deeper than in skin with an intact epidermis. CONCLUSION:
      The affected area by HIFU is dependent on the skin condition and the
      characteristics of the HP and applied fluence. Considerations of these factors
      may be the key to minimize the unwanted adverse effects.

PMID- 27868242
TI  - Assessment of macrovascular endothelial function using pulse wave analysis and
      its association with microvascular reactivity in healthy subjects.
AB  - BACKGROUND: Pulse wave analysis (PWA) and laser Doppler fluximetry (LDF) are non
      invasive methods of assessing macrovascular endothelial function and
      microvascular reactivity respectively. The aim of this study was to assess the
      correlation between macrovascular endothelial function assessed by PWA and
      microvascular reactivity assessed by LDF. METHOD: 297 healthy and non-smoking
      subjects (159 females, mean age (+/-SD) 23.56 +/- 4.54 years) underwent
      microvascular reactivity assessment using LDF followed by macrovascular
      endothelial function assessments using PWA. RESULTS: Pearson's correlation showed
      no correlation between macrovascular endothelial function and microvascular
      reactivity (r = -0.10, P = 0.12). CONCLUSION: There was no significant
      correlation between macrovascular endothelial function assessed by PWA and
      microvascular reactivity assessed by LDF in healthy subjects.

PMID- 27868243
TI  - Simulation of laser-tattoo pigment interaction in a tissue-mimicking phantom
      using Q-switched and long-pulsed lasers.
AB  - BACKGROUND: Laser therapy is the treatment of choice in tattoo removal. However,
      the precise mechanisms of laser-tattoo pigment interactions remain to be
      evaluated. METHODS: We evaluated the geometric patterns of laser-tattoo pigment
      particle interactions using a tattoo pigment-embedded tissue-mimicking (TM)
      phantom. RESULTS: A Q-switched (QS) neodymium-doped yttrium aluminum garnet laser
      was used at settings of 532-, 660-, and 1064-nm wavelengths, single-pulse and
      quick pulse-to-pulse treatment modes, and spot sizes of 4 and 7 mm. Most of the
      laser-tattoo interactions in the experimental conditions formed cocoon-shaped or
      oval photothermal and photoacoustic injury zones, which contained fragmented
      tattoo particles in various sizes depending on the conditions. In addition, a
      long-pulsed 755-nm alexandrite laser was used at a spot size of 6 mm and pulse
      widths of 3, 5, and 10 ms. The finer granular pattern of tattoo destruction was
      observed in TM phantoms treated with 3- and 5-ms pulse durations compared to
      those treated with a 10-ms pulse. CONCLUSION: We outlined various patterns of
      laser-tattoo pigment interactions in a tattoo-embedded TM phantom to predict
      macroscopic tattoo and surrounding tissue reactions after laser treatment for
      tattoo removal.

PMID- 27868244
TI  - DDW 2016 review: Advances in therapeutic upper gastrointestinal endoscopy.
AB  - This is a review of the abstracts presented at Digestive Disease Week 2016, 21-24
      May 2016 in San Diego, CA, USA, focusing on novel advances in therapeutic
      endoscopy of the upper gastrointestinal tract.

PMID- 27868245
TI  - The influence of sex and gonadectomy on hepatic and brain fatty acid composition,
      lipogenesis and beta-oxidation.
AB  - The aim of this study was to investigate the influence of sex and castration of
      rats on liver and brain fatty acid profile and liver mRNA expression of genes
      involved in lipogenesis and beta-oxidation. Castration significantly increased
      body weight and liver index and decreased serum triglyceride content in the
      female rats. The fatty acid composition of the liver tissue was influenced by sex
      and castration. Male rats had higher content of C16:0, C18:1n7, C18:2n6 and
      C22:5n3, while female rats had higher content of C18:0, C20:4n6 and C22:6n3.
      Castration of male rats decreased differences caused by sex for C18:2n6, C20:4n6
      and C22:6n3. Values for C16:1n7 were higher in the castrated male rats in
      comparison with all other groups. Liver phospholipids showed a distribution of
      fatty acids similar to the total lipids. Brain total lipids and phospholipids
      were not influenced by sex or castration. Castration increased ?6D gene
      expression in both the sexes, while ?5D and ?9D increased in females and males
      respectively. Gonadectomy increased expression of the FASN gene in the females
      and decreased CPT1 and ACOX1 gene expression in the liver tissue of male rats.
      The observed results of lipid peroxidation, measured by TBARS, were the lowest in
      the intact females in comparison with all other groups. In conclusion, sex
      strongly influences both SFA and PUFA in liver tissue, and castration decreases
      these differences only for PUFA. Castration also influences the expression of the
      genes involved in lipid metabolism differently in male and female rats, with an
      increase in lipogenic genes in female rats and a decrease in key genes for
      mitochondrial and peroxisomal beta-oxidation in male rats.

PMID- 27868246
TI  - Personal identification based on skin texture features from the forearm and multi
      modal imaging.
AB  - BACKGROUND/PURPOSE: We investigate the use of skin texture features from the
      inner forearm as a means for personal identification. The forearm offers a number
      of potential advantages in that it is a fairly accessible area, and, compared
      with other zones such as fingertips, is less exposed to the elements and more
      shielded from wear. METHODS: We extract and combine skin textural features from
      two imaging devices (optical and capacitive) with the aim of discriminating
      between different individuals. Skin texture images from 43 subjects were acquired
      from three different body parts (back of the hand, forearm and palm); testing
      used the two sensors either separately or in combination. RESULTS: Skin texture
      features from the forearm proved effective for discriminating between different
      individuals with overall recognition accuracy approaching 96%. CONCLUSIONS: We
      found that skin texture features from the forearm are highly individual-specific
      and therefore suitable for personal identification. Interestingly, forearm skin
      texture features yielded significantly better accuracy compared to the skin of
      the back of the hand and of the palm of the same subjects.

PMID- 27868247
TI  - Digestibility, ruminal fermentation, blood metabolites and antioxidant status in
      ewes supplemented with DL-methionine or hydroxy-4 (methylthio) butanoic acid
      isopropyl ester.
AB  - The effects of supplementing ewe diets with either DL-methionine (DL-Met) or 2
      hydroxy-4 (methylthio) butanoic acid isopropyl ester (HMBi) were investigated on
      ruminal in situ degradability of grain and forage diets, in vivo digestibility,
      rumen fermentation, blood metabolites and antioxidant status. Six ruminally
      cannulated ewes were used in a replicated 3 * 3 Latin square design with 28-day
      periods. The dietary treatments were as follows: (i) no supplemental Met
      (control; CON), (ii) DL-Met at 1.2 g/kg DM intake and (iii) HMBi at 1.8 g/kg dry
      matter (DM) intake. Corn grain, barley grain and alfalfa hay were evaluated for
      their ruminal degradability by both in situ incubation and effective
      degradability measurements of DM, neutral detergent fibre (NDF) and acid
      detergent fibre (ADF). Compared to other treatments, HMBi supplementation
      increased (p < 0.05) the digestibility of organic matter, crude protein and NDF
      and also tended (p = 0.08) to increase the digestibility of DM and ADF. Moreover,
      HMBi supplementation increased (p < 0.01) total VFA concentrations, the molar
      proportions of valerate and iso-butyrate in the rumen. Compared to the CON
      treatment, DL-Met and HMBi treatments tended (p = 0.08) to increase the molar
      proportion of acetate but decreased (p < 0.05) ruminal ammonia-N concentration.
      Ewes supplemented with HMBi and DL-Met recorded greater (p < 0.05) serum
      concentrations of glutathione peroxidase, total antioxidant capacity and
      superoxide dismutase than the CON treatment. Serum concentrations of glucose,
      total protein, albumin, high-density lipoprotein and very low-density lipoprotein
      were greater (p < 0.01) and serum urea nitrogen (p < 0.05), malonyl dialdehyde
      and triglyceride were lower (p < 0.02) in the HMBi and DL-Met animals than in the
      CON ewes. The results concluded that HMBi is a very effective form of dietary Met
      supplementation for ewes with a positive effect on digestion, rumen fermentation
      and serum antioxidant function.

PMID- 27868248
TI  - Ring-Opening Regio-, Diastereo-, and Enantioselective 1,3-Chlorochalcogenation of
      Cyclopropyl Carbaldehydes.
AB  - meso-Cyclopropyl carbaldehydes are treated in the presence of an organocatalyst
      with sulfenyl and selenyl chlorides to afford 1,3-chlorochalcogenated products.
      The transformation is achieved by a merged iminium-enamine activation. The
      enantioselective desymmetrization reaction, leading to three adjacent
      stereocenters, furnished the target products in complete regioselectivity and
      moderate to high diastereo- and enantioselectivities (d.r. up to 15:1 and e.r. up
      to 93:7).

PMID- 27868249
TI  - Effects of supplemental dietary vitamin C on quality of semen from Nile tilapia
      (Oreochromis niloticus) breeders.
AB  - The objective of this study was to evaluate the effects of vitamin C on growth
      and quality of semen from Oreochromis niloticus breeders. One hundred and sixty
      males were fed with different levels of vitamin C (0, 261, 599 and 942 mg/kg
      diet). The higher weight values were recorded for 599 (166 g) and 942 (175 g) mg
      of vitamin C/kg diet. Sperm motility, vigour and concentration were higher with
      599 and 942 mg of vitamin C/kg diet. The semen volume, gonadosomatic index and
      plasma protein data from the last week showed a direct relationship with
      increasing levels of vitamin C. No changes were observed in the hepatosomatic
      index and blood glucose. The haematocrit and erythrocyte showed higher values
      estimated by equations derived at 850 and 638 mg vitamin C/kg diet, respectively.
      The leucocytes were inversely proportional to the increasing levels of vitamin C.
      After 100 days of feeding, animals fed the diet containing 942 mg vitamin C/kg
      diet had higher sperm motility, linearity, curvilinear velocity, straight line
      velocity and average path velocity (p < .05). Higher values of beat cross
      frequency were observed in broodfish fed diets containing 942 and 599 mg vitamin
      C/kg. The different vitamin C levels did not cause differences in straightness,
      lateral head displacement and sperm morphology. For Nile tilapia males on
      intensive rearing and handling conditions, vitamin C levels between 599 and 942
      mg/kg may be used for a better performance and quality of semen.

PMID- 27868250
TI  - Effects of Astragalus membranaceus, Codonopsis pilosula and allicin mixture on
      growth performance, nutrient digestibility, faecal microbial shedding, immune
      response and meat quality in finishing pigs.
AB  - A 12-week trial with 120 [(Landrace*Yorkshire)*Duroc] pigs (45.65 +/- 1.93 kg)
      was conducted to evaluate the effects of Astragalus membranaceus, Codonopsis
      pilosula and allicin mixture (HM) supplementation on growth performance, nutrient
      digestibility, faecal microbial shedding, immune response and meat quality in
      finishing pigs. Pigs were allocated to one of three treatments with 0, 0.025%
      (HM1) and 0.05% (HM2) HM supplementation in a randomized complete block design
      according to sex and BW. Each treatment contained 10 replications with four pigs
      (two barrows and two gilts) per pen. Dietary HM resulted in a higher G:F (p <
      0.05) than CON group during weeks 7 to 12 and the overall periods. Pigs fed HM2
      diet had higher ADG than pigs fed CON diet. Pigs fed HM2 supplementation diet led
      to a higher (p < 0.05) apparent total tract digestibility (ATTD) of dry matter
      (DM) and gross energy (GE) than pigs fed CON diet at week 6, while the
      supplementation of HM led to a higher (p < 0.05) ATTD of DM and GE than pigs fed
      CON diet at week 12. The faecal E. coli counts were reduced, and Lactobacillus
      counts were increased by increasing HM supplementation (p < 0.05). Pigs fed HM1
      diet had higher (p < 0.05) WBC concentration than those fed CON and HM2 diets at
      week 6. Pigs fed HM-supplemented diet had higher (p < 0.05) IgG and IgA
      concentrations than those fed CON diet at week 12. Pigs fed HM diet noted better
      (p < 0.05) meat colour and redness value than pigs fed CON diet. Pig fed HM2
      reduced (p < 0.05) the lightness value compared with CON group. In conclusion,
      dietary HM supplementation exerted beneficial effects on growth performance,
      nutrient digestibility, intestinal microbial balance (increased Lactobacillus
      counts and decreased E. coli counts), immune response and meat quality.

PMID- 27868251
TI  - Dietary linseed oil in the maternal diet affects immunoglobulins, tissue fatty
      acid composition and expression of lipid metabolism-related genes in piglets.
AB  - This experiment investigated the effects of supplementing the maternal diet with
      linseed oil (LSO) and soya bean oil (SBO) on immunoglobulins, the fatty acid
      composition and hepatic expression of lipid metabolism-related genes in piglets.
      Multiparous sows (twenty-four per diet) were fed on diets containing a supplement
      of either SBO or LSO during last week of gestation and lactation. The results
      indicated that supplementation of maternal diet with LSO could improve the
      weaning weight of piglets and average daily gain (ADG) (p < 0.05). The
      concentration of immunoglobulin G (IgG) and immunoglobulin A (IgA) was enhanced
      in sow plasma, colostrum and milk by the addition of LSO (p < 0.05). In addition,
      the concentration of 18: 3n-3 fatty acids was higher in the milk of LSO sows.
      Meanwhile, maternal supplementation with LSO increased the levels of plasma IgG,
      IgA and the tissues n-3 polyunsaturated fatty acid (PUFA) in piglets (p < 0.05).
      Correspondingly, the mRNA expression levels of hepatic ?5-desaturase (D5D) and ?6
      desaturase (D6D) were higher, and fatty acid synthase (FAS) was lower in piglets
      from LSO-fed sows when compared with that in the SBO group. In conclusion, LSO
      supplementation of the maternal diet increases immunoglobulins, modifies the
      fatty acid composition and affects the gene of D5D and D6D expression of piglets.

PMID- 27868252
TI  - Predictive equations of selenium accessibility of dry pet foods.
AB  - The trace element selenium is essential to both dogs and cats. Dry diets are
      formulated with a large range of ingredients, which may vary in selenium
      concentration and accessibility. This paper reports equations to predict the
      average in vitro selenium accessibility from dry pet foods based on essential
      dietary nutrient concentrations, including crude protein, amino acids and crude
      fat. Predictive equations were made using stepwise linear regression for extruded
      and pelleted diets. The equations can be used to aid diet formulation to optimize
      selenium accessibility within the diet and to prevent selenium deficiency or
      toxicity.

PMID- 27868253
TI  - The effect of Lupinus albus seeds on digestibility, performance and
      gastrointestinal tract indices in pigs.
AB  - The effect of soya bean meal (SBM) substitution in the diet with white lupine
      (WL) seeds on performances and some parameters of the digestive tract of pigs
      were studied. The digestibility experiment was performed on 30 pigs using
      difference method combined with marker method, where one group was offered basal
      diet and in diet of experimental groups 25% of the basal diet was substituted
      with SBM or WL meal. The growth experiment was conducted on 48 pigs of
      approximately 20 kg body weight. The animals from the control group were fed with
      diet containing SBM, whereas in the experimental groups 50% or 100% of SBM was
      substituted with WL seeds. At the end of the experiment, eight pigs from each
      group were euthanized, and digesta and tissues were sampled. The apparent total
      tract digestibility of crude protein and dry matter was higher (p < 0.05), but
      crude fibre and ether extract were lower (p < 0.05) in the WL seeds than in SBM.
      Substituting 50% of SBM in the control diet with WL seeds did not affect
      significantly pig performance. Total substitution of SBM with WL seeds impacted
      negatively pigs growth and feed intake (p < 0.05), but it did not affect the
      length of villi and crypt depth. It also significantly increased ileum digesta
      viscosity and ammonia concentration in the ileum and caecum digesta. In the ileal
      digesta of animals offered WL seeds, an increased (p < 0.05) total bacterial and
      Enterobacteriaceae numbers were found, whereas reduced number of yeast and mould
      was found in the caecal digesta. The substitution of 50% SBM with WL seeds in the
      growing pig diet did not affect pigs' results, but the total substitution
      significantly decreased the performance of pigs and affected intestinal ecology.

PMID- 27868256
TI  - Ice and the outback: Patterns and prevalence of methamphetamine use in rural
      Australia.
AB  - OBJECTIVE: This study investigated whether lifetime and recent methamphetamine
      use (including crystal methamphetamine) differed among city, regional and rural
      residents and whether particular subpopulations were more at-risk. DESIGN:
      Secondary analyses of the last three National Drug Strategy Household Surveys and
      corresponding Alcohol and Other Drug Treatment Services National Minimum Data
      Sets (AODTS NMDS). SETTING: Australian general population. PARTICIPANTS:
      Australians who completed the 2007 (n = 22 519), 2010 (n = 25 786) and 2013 (n =
      23 512) NDSHS (aged 14 + ); and treatment episodes where the principal drug of
      concern was recorded in the 2006/2007 (n = 139 808), 2009/2010 (n = 139 608) and
      2012/2013 (n = 154 489) AODTS NMDS. MAIN OUTCOME MEASURE(S): To determine whether
      rural Australians were more likely to use methamphetamine than non-rural
      counterparts. RESULTS: Lifetime and recent methamphetamine and recent crystal
      methamphetamine use were significantly higher among rural than other Australians.
      Significantly more rural men and employed rural Australians used methamphetamine
      than their city, regional or Australian counterparts. Rural Australians aged 18
      24 and 25-29 years were significantly more likely to have used methamphetamine in
      their lifetime than city or Australian residents. Rural Australians aged 18-24
      years were significantly more likely to have recently used crystal
      methamphetamine. CONCLUSIONS: Interventions tailored to address the specific and
      unique circumstances of rural settings are required to reduce and prevent
      methamphetamine use, particularly crystal methamphetamine. Scope exists to focus
      prevention efforts on rural workplaces and primary care settings. Greater
      understanding of the higher prevalence of methamphetamine use in rural areas is
      required, plus implementation of comprehensive strategies and optimised treatment
      utilisation.

PMID- 27868254
TI  - Extensive functional redundancy in the regulation of Candida albicans drug
      resistance and morphogenesis by lysine deacetylases Hos2, Hda1, Rpd3 and Rpd31.
AB  - Current treatment efforts for fungal infections are hampered by the limited
      availability of antifungal drugs and by the emergence of drug resistance. A
      powerful strategy to enhance the efficacy of antifungal drugs is to inhibit the
      molecular chaperone Hsp90. Hsp90 governs drug resistance, morphogenesis and
      virulence in a leading fungal pathogen of humans, Candida albicans. Our previous
      work with Saccharomyces cerevisiae established acetylation as a novel mechanism
      of posttranslational control of Hsp90 function in fungi. We implicated lysine
      deacetylases (KDACs) as key regulators of resistance to the most widely deployed
      class of antifungals, the azoles, in both S. cerevisiae and C. albicans. Here, we
      demonstrate high levels of functional redundancy among the KDACs that are
      important for regulating Hsp90 function. We identify Hos2, Hda1, Rpd3 and Rpd31
      as the KDACs mediating azole resistance and morphogenesis in C. albicans.
      Furthermore, we identify lysine 30 and 271 as critical acetylation sites on C.
      albicans Hsp90, and substitutions at these residues compromise Hsp90 function.
      Finally, we show that pharmacological inhibition of KDACs phenocopies
      pharmacological inhibition of Hsp90 and abrogates Hsp90-dependent azole
      resistance in numerous Candida species. This work illuminates new facets to the
      impact of KDACs on fungal drug resistance and morphogenesis, provides important
      insights into the divergence of the C. albicans Hsp90 regulatory network and
      reveals new targets for development of antifungal drugs.

PMID- 27868255
TI  - Regulatory gene mutation: a driving force behind group a Streptococcus strain-
      and serotype-specific variation.
AB  - Data from multiple bacterial pathogens are consistent with regulator-encoding
      genes having higher mutation frequencies than the genome average. Such mutations
      drive both strain- and type- (e.g., serotype, haplotype) specific phenotypic
      heterogeneity, and may challenge public health due to the potential of variants
      to circumvent established treatment and/or preventative regimes. Here, using the
      human bacterial pathogen the group A Streptococcus (GAS; S. pyogenes) as a model
      organism, we review the types and regulatory-, phenotypic-, and disease-specific
      consequences of naturally occurring regulatory gene mutations. Strain-specific
      regulator mutations that will be discussed include examples that transform
      isolates into hyper-invasive forms by enhancing expression of immunomodulatory
      virulence factors, and examples that promote asymptomatic carriage of the
      organism. The discussion of serotype-specific regulator mutations focuses on
      serotype M3 GAS isolates, and how the identified rewiring of regulatory networks
      in this serotype may be contributing to a decades old epidemiological association
      of M3 isolates with particularly severe invasive infections. We conclude that
      mutation plays an outsized role in GAS pathogenesis and has clinical relevance.
      Given the phenotypic variability associated with regulatory gene mutations, the
      rapid examination of these genes in infecting isolates may inform with respect to
      potential patient complications and treatment options.

PMID- 27868257
TI  - The effect of maize silage type on the performances and methane emission of dairy
      cattle.
AB  - To examine whether type of maize silage is important for milk production
      performances, maize silage LG30224 (LG) was compared with Falkone (FA), the
      latter having a 4.0% points lower rumen NDF digestibility and 19 g/kg dry matter
      (DM) more starch. To bridge the lower energy content of FA, a third treatment was
      involved by adding maize meal (MM) in a ratio of 92/8 on DM (FA+MM). Maize and
      grass silage were fed ad libitum in a ratio of 65/35 on DM basis. Concentrates
      were supplemented individually to meet energy and protein requirements. The
      experiment was set up as a Latin square with three groups of nine Holstein cows
      during three periods of 3 weeks. In the last 2 weeks of each period, DM intake
      (DMI) and milk performances were measured. Each group included one cannulated cow
      to study effects on rumen fermentation. During the last 4 days of each period,
      two cows from each group were placed in gas exchange chambers to measure nutrient
      digestibility and methane production. Total DMI was higher (p < 0.05) for FA+MM
      (20.8 kg/day) than for FA (20.3 kg/day), while DMI for LG was intermediate (20.6
      kg/day). Treatment did not affect milk production nor composition, whereas fat
      protein-corrected milk was higher for LG (30.5 kg/day) and FA+MM (30.3 kg/day)
      than for FA (29.9 kg/day). The ration did not affect pH nor volatile fatty acid
      composition in the rumen. Further, total tract digestibility of OM, crude
      protein, NDF and starch did not differ among treatments. The ration with LG gave
      higher methane production per day and per kg NDF intake than both rations with
      FA, but the difference was not significant when expressed per kg DMI or FPCM.
      Thus, maize silage type is of little importance for milk production if energy and
      physical structure requirements are met.

PMID- 27868258
TI  - The first familial cases of epidermolysis bullosa simplex, generalized severe
      with p.Asn176Ser in KRT5 revealing the clinical chronology.

PMID- 27868259
TI  - Effectiveness of an experiential workshop for enhancing helping professionals'
      self-competence in death work in Hong Kong: a randomised controlled trial.
AB  - Helping professionals require self-competence in coping with the existential and
      emotional challenges of death work. Previous training often focused on knowledge
      and skills rather than on this competence. This study aimed to examine the
      effectiveness of a 3-day workshop in Hong Kong to enhance helping professionals'
      self-competence in death work. A randomised controlled trial was conducted to
      examine the effects of the training between January and May 2014. Targeted
      participants were helping professionals who had been doing death work for at
      least 6 months. The 112 participants were openly recruited from hospitals and
      NGOs and were assigned to an intervention group or a waitlist control group. Data
      were collected at pre-intervention and post-intervention. Primary outcome was
      self-competence in death work. All participants were grouped for analysing the
      changes in outcomes at pre-intervention, post-intervention and 3-month follow-up.
      Participants in the intervention group experienced a significant increase in the
      total score of the Self-competence in Death Work Scale (SC-DWS) and in scores of
      the Existential and Emotional subscales of SC-DWS. The positive effects of
      training on self-competence in death work were maintained at the 3-month follow
      up. This study provides evidence of the effectiveness of training in enhancing
      helping professionals' self-competence in death work. Further research is
      required to examine the long-term effects of training.

PMID- 27868260
TI  - An experimental study of adolescent sleep restriction during a simulated school
      week: changes in phase, sleep staging, performance and sleepiness.
AB  - This laboratory study investigated the impact of restricted sleep during a
      simulated school week on circadian phase, sleep stages and daytime functioning.
      Changes were examined across and within days and during a simulated weekend
      recovery. Participants were 12 healthy secondary school students (six male) aged
      15-17 years [mean = 16.1 years, standard deviation (SD) = 0.9]. After 2 nights
      with 10 h (21:30-07:30 hours), time in bed was restricted to 5 h for 5 nights
      (02:30-07:30 hours), then returned to 10 h time in bed for 2 nights (21:30-07:30
      hours). Saliva was collected in dim light on the first and last sleep restriction
      nights to measure melatonin onset phase. Sleep was recorded polysomnographically,
      and the Psychomotor Vigilance Task (PVT) and Karolinska Sleepiness Scale were
      undertaken 3-hourly while awake. Average phase delay measured by melatonin was 3
      h (SD = 50 min). Compared to baseline, sleep during the restriction period
      contained a smaller percentage of Stages 1 and 2 and rapid eye movement (REM) and
      a greater percentage of Stage 4. PVT lapses increased significantly during sleep
      restriction and did not return to baseline levels during recovery. Subjective
      sleepiness showed a similar pattern during restriction, but returned to baseline
      levels during recovery. Results suggest that sustained attention in adolescents
      is affected negatively by sleep restriction, particularly in the early morning,
      and that a weekend of recovery sleep is insufficient to restore performance. The
      discrepancy between sleepiness ratings and performance may indicate a lack of
      perception of this residual impairment.

PMID- 27868261
TI  - Mental Health of Transgender Veterans of the Iraq and Afghanistan Conflicts Who
      Experienced Military Sexual Trauma.
AB  - Little is known about military sexual trauma (MST) in transgender veterans. To
      address this gap, we examined archival data regarding transgender veterans from
      the Iraq and Afghanistan conflicts. There were 332 transgender veterans treated
      at the Veterans Health Administration between 2000 and 2013 (78 men, 254 women;
      mean age 33.86 years), with most being non-Hispanic White. Transgender status and
      mental health conditions were identified using the International Classification
      of Diseases, 9th Revision (ICD-9; World Health Organization, 1980) codes and
      chart review. Men and women were analyzed separately, using contingency tables
      and chi2 testing for categorical variables and t tests for continuous variables.
      Likelihood of having a mental health condition and MST were examined using
      logistic regression. Among the 15% of participants who experienced MST, MST was
      associated with the likelihood of posttraumatic stress disorder, adjusted OR =
      6.09, 95% confidence interval (CI) [1.22, 30.44] and personality disorder, OR =
      3.86, 95% CI [1.05, 14.22] for men and with depressive, OR = 3.33, 95% CI [1.12,
      9.93], bipolar, OR = 2.87, 95% CI [1.12, 7.44], posttraumatic stress, OR = 2.42,
      [1.11, 5.24], and personality disorder, OR = 4.61, 95% CI [2.02, 10.52] for
      women. Implications include that medical forms should include gender identity and
      biological gender and that MST treatment should be culturally competent.

PMID- 27868262
TI  - Adipocytes enhance expression of osteoclast adhesion-related molecules through
      the CXCL12/CXCR4 signalling pathway.
AB  - OBJECTIVES: The purpose of this study was to investigate effects of adipocytes on
      osteoclast adhesion-related molecules. MATERIALS AND METHODS: ST2 cells, a cloned
      stromal cell line from mouse bone marrow, able to differentiate into adipocytes,
      were cultured in serum-free alpha-MEM which was then collected to be used as
      adipocyte-conditioned medium (ADIPO CM). RAW264.7 cells were cultured in ADIPO CM
      in the presence of RANKL, and bone marrow-derived macrophages were cultured in
      ADIPO CM in the presence of RANKL and macrophage-colony stimulating factor to
      induce osteoclast differentiation. TRAP staining, resorption pit assay, qRT-PCR
      and western blotting assays were performed. RESULTS: ELISAs revealed that CXCL12
      was abundant in ADIPO CM and CCK-8 assay revealed no proliferation of RAW264.7
      cells after exogenous CXCL12 treatment. ADIPO CM enhanced osteoclast formation
      and resorption, both by RAW264.7 cells and BMMs. In addition, exogenous CXCL12
      efficiently potentiated formation of TRAP-positive osteoclast and resorption by
      RAW264.7 cells. Western blotting and qRT-PCR suggested that ADIPO CM or combined
      treatment with exogenous CXCL12 caused significant increase in expression of
      NFAT2, src and osteoclast adhesion-related molecules, including beta3 integrin,
      CD44 and osteopontin. However, these promotional effects were largely abrogated
      on treatment of AMD3100, a CXCR4 antagonist. CONCLUSIONS: Adipocytes promoted
      osteoclast differentiation, function and expression of adhesion-related molecules
      through the CXCL12/CXCR4 signalling pathway.

PMID- 27868263
TI  - Nurses as family caregivers - barriers and enablers facing nurses caring for
      children, parents or both.
AB  - AIMS: To examine the dual caregiving and nursing responsibilities of nurses in
      New Zealand with a view to identifying potential strategies, policies and
      employment practices that may help to retain nurses with caregiving
      responsibilities in the workplace. BACKGROUND: As the nursing workforce ages,
      child-bearing is delayed and older family members are living longer, family
      caregiving responsibilities are impacting more on the working life of nurses.
      This may complicate accurate workforce planning assumptions. METHOD: An
      explorative, descriptive design using interviews and focus groups with 28
      registered nurses with family caregiving responsibilities. RESULTS: A depth of
      (largely hidden) experience was exposed revealing considerable guilt, physical,
      emotional and financial hardship. Regardless of whether the nurse chose to work
      or had to for financial reasons, family always came first. CONCLUSIONS:
      Demographic and societal changes related to caregiving may have profound
      implications for nursing. Workplace support is essential to ensure that nurses
      are able to continue to work. IMPLICATIONS FOR NURSING MANAGEMENT: Increased
      awareness, support, flexibility and specific planning are required to retain
      nurses with family caregiving responsibilities.

PMID- 27868264
TI  - Profiles of children with Down syndrome who meet screening criteria for autism
      spectrum disorder (ASD): a comparison with children diagnosed with ASD attending
      specialist schools.
AB  - BACKGROUND: Recent research suggests that around 16% to 18% of children with Down
      syndrome (DS) also meet diagnostic criteria for autism spectrum disorder (ASD).
      However, there are indications that profiles of autism symptoms in this group may
      vary from those typically described in children with ASD. METHOD: Rates of autism
      symptoms and emotional and behavioural problems among children with DS who
      screened positive for ASD on the Social Communication Questionnaire (SCQ) (n =
      183) were compared with a group of children with clinical diagnoses of ASD (n =
      189) attending specialist schools in the UK. Groups were matched for age and
      approximate language level (use of phrase speech). RESULTS: Profiles of autistic
      symptoms in the two groups were generally similar, but children with DS meeting
      ASD cut-off on the SCQ tended to show fewer problems in reciprocal social
      interaction than those in the ASD group. They also showed slightly lower rates of
      emotional and peer-related problems. The results mostly confirm findings from a
      previous study in which the original validation sample for the SCQ was used as a
      comparison group. CONCLUSION: Findings suggest that children with DS who meet
      screening criteria for ASD show similar profiles of communication and repetitive
      behaviours to those typically described in autism. However, they tend to have
      relatively milder social difficulties. It is important that clinicians are aware
      of this difference if children with DS and ASD are to be correctly diagnosed and
      eligible for specialist intervention and education services.

PMID- 27868265
TI  - High-throughput physiological phenotyping and screening system for the
      characterization of plant-environment interactions.
AB  - We present a simple and effective high-throughput experimental platform for
      simultaneous and continuous monitoring of water relations in the soil-plant
      atmosphere continuum of numerous plants under dynamic environmental conditions.
      This system provides a simultaneously measured, detailed physiological response
      profile for each plant in the array, over time periods ranging from a few minutes
      to the entire growing season, under normal, stress and recovery conditions and at
      any phenological stage. Three probes for each pot in the array and a specially
      designed algorithm enable detailed water-relations characterization of whole
      plant transpiration, biomass gain, stomatal conductance and root flux. They also
      enable quantitative calculation of the whole plant water-use efficiency and
      relative water content at high resolution under dynamic soil and atmospheric
      conditions. The system has no moving parts and can fit into many growing
      environments. A screening of 65 introgression lines of a wild tomato species
      (Solanum pennellii) crossed with cultivated tomato (S. lycopersicum), using our
      system and conventional gas-exchange tools, confirmed the accuracy of the system
      as well as its diagnostic capabilities. The use of this high-throughput
      diagnostic screening method is discussed in light of the gaps in our
      understanding of the genetic regulation of whole-plant performance, particularly
      under abiotic stress.

PMID- 27868266
TI  - Reducing falls in a model of impaired cognitive control of movement (Commentary
      on Kucinski et al.).

PMID- 27868267
TI  - Reduced microRNA-188-3p expression contributes to apoptosis of spermatogenic
      cells in patients with azoospermia.
AB  - BACKGROUND AND AIMS: Human mutL homologl (MLH1) works coordinately in sequential
      steps to initiate repair of DNA mismatches, and aberrant MLH1 expression is
      related to spermatogenetic malfunction. In the present study, MLH1 expression in
      patients with azoospermia was investigated, and moderating effects of miR-188-3p
      on MLH1 expression and spermatogenesis were identified. METHODS: Testicular
      tissues from 16 patients with obstructive azoospermia (OA) and non-obstructive
      azoospermia (NOA), and tissues of eight healthy patients were collected. Real
      time PCR, Western blotting and immunohistochemical staining were used to detect
      MLH1 expression. Chromatin immunoprecipitation assay and luciferase reporter
      assay were performed to evaluate histone acetylation level of miR-188-3p and
      relationships between miR-188-3p and MLH1. RESULTS: Testicular MLH1 expression at
      mRNA and protein levels was significantly increased, while miR-188-3p expression
      was lower in patients with OA and NOA than that in controls. Reduced histone
      acetylation level of miR-188-3p promoter was observed in patients with
      azoospermia. Overexpression/inhibition of HDAC1, but not HDAC2, contributed to
      the significant reduction/increase of miR-188-3p expression. miR-188-3p targeted
      3' UTR of MLH1 and regulated MLH1 expression. miR-188-3p inhibitor led to
      elevation of apoptotic level of spermatogenic cells in mice, while this effect
      was reversed by si-MLH1. CONCLUSION: Down-regulation of miR-188-3p by reducing
      histone acetylation up-regulated MLH1 expression and contributed to promotion of
      apoptosis in spermatogenic cells, in patients with azoospermia.

PMID- 27868268
TI  - p38 MAPK pathway is essential for self-renewal of mouse male germline stem cells
      (mGSCs).
AB  - OBJECTIVES: Male germline stem cells (mGSCs), also called spermatogonial stem
      cells (SSCs), constantly generate spermatozoa in male animals. A number of
      preliminary studies on mechanisms of mGSC self-renewal have previously been
      conducted, revealing that several factors are involved in this regulated process.
      The p38 MAPK pathway is widely conserved in multiple cell types in vivo, and
      plays an important role in cell proliferation, differentiation, inflammation and
      apoptosis. However, its role in self-renewal of mGSCs has not hitherto been
      determined. MATERIALS AND METHODS: Here, the mouse mGSCs were cultured and their
      identity was verified by semi-RT-PCR, alkaline phosphatase (AP) staining and
      immunofluorescence staining. Then, the p38 MAPK pathway was blocked by p38 MAPK
      specific inhibitor SB202190. mGSC self-renewal ability was then analysed by
      observation of morphology, cell number, cell growth analysis, TUNEL incorporation
      assay and cell cycle analysis. RESULTS: Results showed that mouse mGSC self
      renewal ability was significantly inhibited by SB202190. CONCLUSIONS: This study
      showed for the first time that the p38 MAPK pathway plays a key role in
      maintaining self-renewal capacity of mouse mGSCs, which offers a new self-renewal
      pathway for these cells and contributes to overall knowledge of the mechanisms of
      mGSC self-renewal.

PMID- 27868269
TI  - Estimating Breast Mass-Density: A Retrospective Analysis of Radiological Data.

PMID- 27868270
TI  - Zika virus, HSV-2 and placenta.

PMID- 27868271
TI  - Lone-Actor Terrorist Target Choice.
AB  - Lone-actor terrorist attacks have risen to the forefront of the public's
      consciousness in the past few years. Some of these attacks were conducted against
      public officials. The rise of hard-to-detect, low-tech attacks may lead to more
      public officials being targeted. This paper explores whether different behavioral
      traits are apparent within a sample of lone-actor terrorists who plotted against
      high-value targets (including public officials) than within a sample of lone
      actors who plotted against members of the public. Utilizing a unique dataset of
      111 lone-actor terrorists, we test a series of hypotheses related to attack
      capability and operational security. The results indicate that very little
      differentiates those who attack high-value targets from those who attack members
      of the public. We conclude with a series of illustrations to theorize why this
      may be the case. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27868272
TI  - Introduction to this Issue: International Perspectives on the Protection of
      Public Officials.

PMID- 27868273
TI  - From Assassination to Protection of Public Officials: An Introductory Editorial.

PMID- 27868274
TI  - APCI as an innovative ionization mode compared with EI and CI for the analysis of
      a large range of organophosphate esters using GC-MS/MS.
AB  - Organophosphate esters (OPEs) are chemical compounds incorporated into materials
      as flame-proof and/or plasticizing agents. In this work, 13 non-halogenated and 5
      halogenated OPEs were studied. Their mass spectra were interpreted and compared
      in terms of fragmentation patterns and dominant ions via various ionization
      techniques [electron ionization (EI) and chemical ionization (CI) under vacuum
      and corona discharge atmospheric pressure chemical ionization (APCI)] on gas
      chromatography coupled to mass spectrometry (GC-MS). The novelty of this paper
      relies on the investigation of APCI technique for the analysis of OPEs via
      favored protonation mechanism, where the mass spectra were mostly dominated by
      the quasi-molecular ion [M + H]+ . The EI mass spectra were dominated by ions
      such as [H4 PO4 ]+ , [M-R]+ , [M-Cl]+ , and [M-Br]+ , and for some non
      halogenated aryl OPEs, [M]+? was also observed. The CI mass spectra in positive
      mode were dominated by [M + H]+ and sometimes by [M-R]+ , while in negative mode,
      [M-R]- and more particularly [X]- and [X2 ]-? were mainly observed for the
      halogenated OPEs. Both EI and APCI techniques showed promising results for
      further development of instrumental method operating in selective reaction
      monitoring mode. Instrumental detection limits by using APCI mode were 2.5 to 25
      times lower than using EI mode for the non-brominated OPEs, while they were
      determined at 50-100 times lower by the APCI mode than by the EI mode, for the
      two brominated OPEs. The method was applied to fish samples, and monitored
      transitions by using APCI mode showed higher specificity but lower stability
      compared with EI mode. The sensitivity in terms of signal-to-noise ratio varying
      from one compound to another. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27868276
TI  - Platelets are a possible regulator of human endometrial re-epithelialization
      during menstruation.
AB  - PROBLEM: The human endometrium periodically breaks down and regenerates. As
      platelets have been reported to contribute to the tissue remodeling process, we
      examined the possible involvement of platelets in endometrial regeneration.
      METHOD OF STUDY: The distribution of extravasating platelets throughout the
      menstrual cycle was immunohistochemically examined using human endometrial
      tissues. EM-E6/E7/hTERT cells, a human endometrial epithelial cell-derived
      immortalized cell line, were co-cultured with platelets, and the effects of
      platelets on the epithelialization response of EM-E6/E7/hTERT cells were
      investigated by attachment and permeability assays, immunohistochemical staining,
      and Western blot analysis. RESULTS: Immunohistochemical study showed numerous
      extravasated platelets in the subluminar stroma during the menstrual phase. The
      platelets promoted the cell-to-matrigel attachment of EM-E6/E7/hTERT cells
      concomitantly with the phosphorylation of focal adhesion kinase. They also
      promoted cell-to-cell contact among EM-E6/E7/hTERT cells in parallel with E
      cadherin expression. CONCLUSION: These results indicate the possible involvement
      of platelets in the endometrial epithelial re-epithelialization process.

PMID- 27868275
TI  - Effectiveness and safety of drugs used for stroke prevention in a cohort of non
      valvular atrial fibrillation patients from a primary care electronic database.
AB  - PURPOSE: The aim of this study was to assess effectiveness and safety of
      antithrombotics for stroke prevention in non-valvular atrial fibrillation in real
      use conditions. METHODS: We used a population-based retrospective cohort study.
      Information emerges from SIDIAP, a database containing anonymized information
      from electronic health records from 274 primary healthcare centres of the Catalan
      Health Institute, Catalonia (Spain), with a reference population of 5 835 000
      people. Population includes all adults with a new diagnosis of non-valvular
      atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of
      antithrombotics' effectiveness was stroke. The main outcomes of safety were
      cerebral and gastrointestinal haemorrhages. We also estimated all-cause
      mortality. We used multivariable Cox proportional hazard models to examine
      association between antithrombotic treatment and main outcomes. RESULTS: We
      included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated
      on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We
      found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence
      interval (CI), 0.58-0.91), also seen in patients with CHADS2  >= 2, HR 0.65
      (95%CI, 0.49-0.86), and CHA2 DS2 -VASc >= 2, HR 0.66 (95%CI, 0.52-0.84). We
      observed a higher risk of digestive bleeding with antiplatelets, HR 1.32 (95%CI,
      1.01-1.73). Both VKA and antiplatelets were associated with reduction of all
      cause mortality risk; HR 0.55 (95%CI, 0.49-0.62) and HR 0.89 (95%CI, 0.80-0.97),
      respectively. CONCLUSIONS: This study found a stroke-risk reduction associated
      with VKA and an increased risk of gastrointestinal bleeding associated with
      platelet-aggregation inhibitors in comparison with untreated patients. Both
      antithrombotic groups showed a reduction in all-cause mortality. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27868277
TI  - Outpatient antidepressant drug use in children and adolescents in Germany between
      2004 and 2011.
AB  - PURPOSE: Recent studies on the utilization of antidepressant drugs in minors are
      scarce, methodologically limited, and do not factor in off-label use
      sufficiently. Beyond that, little is known about the short treatment durations
      that have been observed for many young antidepressant users. The present study
      examined antidepressant use in pediatric patients aged 0 to 17 years over time,
      investigated changes regarding the prescribed drugs, analyzed underlying
      diagnoses, and assessed the rate of off-label use. METHODS: We used claims data
      of roughly two million individuals to calculate annual prevalence and incidence
      rates of antidepressant prescriptions for the years 2004 to 2011. Analyses were
      stratified by age, sex, and drug type. For antidepressant users, numbers of
      prescriptions, frequencies of disorders/diseases, and specialties of the
      prescribing physicians were examined. The share of off-label prescriptions was
      calculated for each year. RESULTS: The prescription prevalence of antidepressants
      ranged between 1.7 and 2.1 per 1000 minors. The use of tricyclic antidepressants
      decreased from 0.9 to 0.6 prescriptions per 1000 minors, while the use of
      selective serotonin reuptake inhibitors increased from 0.5 to 1.1. Of the
      patients with an antidepressant prescription, 46.4% only received one
      prescription. Depression was by far the most frequent diagnosis among all
      antidepressant users as well as among subjects with only one prescription. In
      2011, 36.3% of all prescriptions were off-label. CONCLUSIONS: The high proportion
      of single prescriptions, even in patients with a diagnosed depression, and the
      high rate of off-label use are particularly noteworthy and should be further
      investigated in future studies. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27868278
TI  - Differences in VigiBase(r) reporting of aminoglycoside and capreomycin-suspected
      ototoxicity during tuberculosis treatment.
AB  - PURPOSE: To evaluate the association between the use of streptomycin, amikacin,
      kanamycin and capreomycin in tuberculosis (TB) treatment and the
      pharmacovigilance reporting of ototoxicity (deafness or hearing loss, tinnitus
      and vertigo). Second, to analyze patient demographic and geographic factors that
      influence the reporting of ototoxicity in TB treatment. METHODS: A case/non-case
      disproportionality analysis of the VigiBase(r) individual case safety reports
      (ICSRs) of patients treated for TB using multidrug regimens that contain either
      of streptomycin, amikacin, kanamycin or capreomycin. Cases were reports of
      ototoxicity; non-cases were other adverse drug reactions (ADRs). The unit of
      analysis was the drug-ADR pair. We calculated reporting odds ratios (RORs) and
      their 95% confidence intervals (CI). The referent drug was streptomycin. RESULTS:
      By June 2014, there were 3361 drug-ADR pairs in VigiBase(r) (1693 ICSRs) where
      the parenteral administration of the four drugs for TB treatment was suspected of
      causing the reported ADRs. Deafness, tinnitus and vertigo were reported in 576
      drug-ADR pairs (cases), the rest being other ADRs (non-cases). Reporting of
      deafness was most disproportionately associated with amikacin use (ROR 9.3; 95%CI
      3.8-23.0), followed by kanamycin use (ROR 4.3; 95%CI 1.3-14.2). Reporting of
      vertigo was inversely associated with capreomycin use (ROR 0.1; 95%CI 0.01-0.4).
      Geographic region affected the reporting of ototoxicity while age and sex did
      not. CONCLUSION: Spontaneous reporting of deafness cases within VigiBase(r) was
      most disproportionately associated with amikacin use, followed by kanamycin.
      There were regional variations in the global reporting of ototoxicity. These
      findings should be verified through a follow up study. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27868279
TI  - Involvement of DPP IV/CD26 in cutaneous wound healing process in mice.
AB  - Dipeptidyl peptidase IV (DPP IV/CD26) is a widely distributed multifunctional
      protein that plays a significant role in different physiological as well as
      pathological processes having a broad spectrum of bioactive substrates and
      immunomodulative properties. It has potential influence on different processes
      crucial for wound healing, including cell adhesion, migration, apoptosis, and
      extracellular matrix degradation. However, despite its known enzymatic and
      immunomodulative functions, limited data characterize the role of DPP IV/CD26 in
      cutaneous wound healing mechanisms. The aim of this study was to investigate the
      process of wound healing in conditions of CD26 deficiency in order to obtain
      better insights on the role of DPP IV/CD26 in cutaneous regeneration.
      Experimental wounds were made on the dorsal part of CD26 deficient (CD26-/- ) and
      wild-type mice (C57BL/6). The process of cutaneous wound healing was monitored on
      defined time schedule postwounding by macroscopic, microscopic, and biochemical
      analyses. Obtained results revealed a better rate of wound closure,
      revascularization and cell proliferation in CD26-/- mice, with enhanced local
      expression of hypoxia-inducible factor 1alpha and vascular endothelial growth
      factor. CD26 deficiency induced prompt macrophage recruitment at the site of skin
      damage but did not influence mobilization of T-cells in comparison with wild-type
      mice. CD26-/- mice have significantly higher values of IP-10 in serum and control
      skins compared with wild-type mice but values in wounds did not differ
      significantly on days 2, 4, and 7 of wound healing. DPP IV/CD26 activity was
      found to be decreased 4 days postwounding in serum and 2, 4, and 7 days
      postwounding in wounds of wild-type animals compared with control skins. These
      findings contribute to better understanding of wound healing mechanisms and could
      give a support in finding new therapeutic approaches for wound healing and tissue
      regeneration.

PMID- 27868280
TI  - Chlamydial infection enhances expression of the polymeric immunoglobulin receptor
      (pIgR) and transcytosis of IgA.
AB  - PROBLEM: The pIgR mediates transport of IgA into the lumen of mucosal tissues
      preventing pathogenic infection. Despite this, the expression of pIgR during
      chlamydial infections of the male and female reproductive tracts remains poorly
      understood. METHOD OF STUDY: The expression of pIgR in response to hormone
      cycling or over the course of chlamydial infection was determined in vitro and in
      vivo by Western blot or immunohistochemistry. RESULTS: PIgR was upregulated in
      response to Chlamydia spp. infection of human epithelia, in both male and female
      mouse reproductive tracts. PIgR expression was found to be highest during estrus
      in the cervicovaginal and uterine epithelia and lowest during diestrus or
      following hormonal synchronization with Depo-Provera. Chlamydial infection of
      mice mediates upregulation of pIgR and transcytosis of IgA into the lumen.
      CONCLUSIONS: Our results suggest that chlamydial infection enhances IgA secretion
      and pIgR expression by epithelia in the lower reproductive tracts of females and
      males, and hormone synchronization downregulates pIgR expression and transcytosis
      of IgA prior to challenge.

PMID- 27868281
TI  - Long-term benefit of transoral incisionless fundoplication using the esophyx
      device for the management of gastroesophageal reflux disease responsive to
      medical therapy.
AB  - Transoral incisionless fundoplication (TIF) using the EsophyX device has been
      shown to be effective and safe in patients with Gastroesophageal reflux disease
      (GERD); however, the subset of patients that would mostly benefit from this
      technique remains unknown. The aim of this study was to evaluate the long-term
      efficacy and safety of the TIF procedure in patients with a history of
      esophagitis or proven chronic GERD who have achieved symptom control with the
      administration of proton pump inhibitors (PPIs) but did not wish to continue
      receiving medications for life. Forty-five patients with typical GERD symptoms
      (heartburn, regurgitation, chest pain) and a history of esophagitis grade A and B
      or proven GERD by esophageal pH monitoring underwent TIF using Esophyx. Patients
      with eosphagitis C and D or those with large hiatal hernias (>2 cm in length)
      were excluded. The primary clinical effectiveness measure was GERD symptom
      elimination at follow up based on normalization of the GERD health related
      quality of life (GERD-HRQL) questionnaire. After a median follow up period of 59
      months (36-75) the median GERD-HRQL scores improved significantly from 27 (2-45)
      at baseline to 4 (0-26) (P < 0.001) in the 44 patients completing the study.
      Heartburn was eliminated in 12 out of the 21 patients included (57.1%),
      regurgitation was eliminated in 15 out of the 17 patients included (88.2%) and
      finally chest pain was eliminated in 5 patients out of the six patients included
      (83.3%). Overall, 32 patients out of the 44 patients (72.7%) that completed the
      study follow up reported elimination of their main symptom, without the need for
      PPI administration (none PPI usage). Furthermore, six more patients (13.6%), five
      with heartburn, and one with regurgitation reported half PPI dose taken for <50%
      of the preceding follow up period (occasional PPI usage), while six more patients
      (four with heartburn, one with regurgitation, and one with chest pain) reported
      full or half PPI dose taken for more than 50% of the preceding follow up period
      (daily PPI usage). Creation of an esophagogastric fundoplication using the
      EsophyX device abolished reflux symptoms in 72.7% of PPI-responsive GERD patients
      at a median 59 month follow-up.

PMID- 27868282
TI  - Validation of Stevens-Johnson syndrome or toxic epidermal necrolysis diagnoses in
      the Clinical Practice Research Datalink.
AB  - PURPOSE: To evaluate the validity of recorded diagnoses of Stevens-Johnson
      syndrome (SJS) and toxic epidermal necrolysis (TEN) in the Clinical Practice
      Research Datalink (CPRD). METHODS: We identified patients with a diagnosis of SJS
      or TEN between 1995 and 2013 in the CPRD. We reviewed information from patient
      records, free text, and hospital episode statistics (HES) data, and excluded
      patients with no indication of a secondary care referral. Remaining patients were
      classified as probable, possible, or unlikely cases of SJS/TEN by two specialised
      clinicians or based on pre-defined classification criteria. We quantified
      positive predictive values (PPV) for all SJS/TEN patients and for patients
      categorised as 'probable/possible' cases of SJS/TEN, based on a representative
      subsample of 118 patients for whom we had unequivocal information (original
      discharge letters or HES data). RESULTS: We identified 1324 patients with a
      diagnosis of SJS/TEN, among whom 638 had a secondary care referral recorded. Of
      those, 565 were classified as probable or possible cases after expert review. We
      calculated a PPV of 0.79 (95% CI, 0.71-0.86) for all SJS/TEN patients with a
      recorded secondary care referral, and a PPV of 0.87 (95% CI, 0.81-0.93) for
      probable/possible cases. After excluding 14 false positive patients, our study
      population consisted of 551 SJS/TEN patients. CONCLUSIONS: Diagnoses of SJS/TEN
      are recorded with moderate diagnostic accuracy in the CPRD, which was
      substantially improved by additional expert review of all available information.
      We established a large population-based SJS/TEN study population of high
      diagnostic validity from the CPRD. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27868283
TI  - Non-invasive evaluation of skin tension lines with elastic waves.
AB  - BACKGROUND: Since their discovery by Karl Langer in the 19th Century, Skin
      Tension Lines (STLs) have been used by surgeons to decide the location and
      orientation of an incision. Although these lines are patient-specific, most
      surgeons rely on generic maps to determine their orientation. Beyond the
      imprecise pinch test, there remains no accepted method for determining STLs in
      vivo. METHODS: (i) The speed of an elastic motion travelling radially on the skin
      of canine cadavers was measured with a commercial device called the
      Reviscometer(r) . (ii) Similar to the original experiments conducted by Karl
      Langer, circular excisions were made on the skin and the geometric changes to the
      resulting wounds and excised samples were used to determine the orientation of
      STLs. RESULTS: A marked anisotropy in the speed of the elastic wave travelling
      radially was observed. The orientation of the fastest wave was found to correlate
      with the orientation of the elongated wound (P<0.001, R2 =74%). Similarly, the
      orientation of fastest wave was the same for both in vivo and excised isolated
      samples, indicating that the STLs have a structural basis. Resulting wounds
      expanded by an average area of 9% (+16% along STL and -10% across) while excised
      skin shrunk by an average area of 33% (23% along STL and 10% across). CONCLUSION:
      Elastic surface wave propagation has been validated experimentally as a robust
      method for determining the orientation of STLs non-destructively and non
      invasively. This study has implications for the identification of STLs and for
      the prediction of skin tension levels, both important factors in both human and
      veterinary reconstructive surgery.

PMID- 27868284
TI  - Speciation in a keystone plant genus is driven by elevation: a case study in New
      Guinean Ficus.
AB  - Much of the world's insect and plant biodiversity is found in tropical and
      subtropical 'hotspots', which often include long elevational gradients. These
      gradients may function as 'diversity pumps' and contribute to both regional and
      local species richness. Climactic conditions on such gradients often change
      rapidly along short vertical distances and may result in local adaptation and
      high levels of population genetic structure in plants and insects. We
      investigated the population genetic structure of two species of Ficus (Moraceae)
      along a continuously forested elevational gradient in Papua New Guinea. This
      speciose plant genus is pollinated by tiny, species-specific and highly coevolved
      chalcid wasps (Agaonidae) and represented by at least 73 species at our study
      gradient. We present results from two species of Ficus sampled from six
      elevations between 200 m and 2700 m a.s.l. (almost the entire elevational range
      of the genus) and 10 polymorphic microsatellite loci. These results show that
      strong barriers to gene flow exist between 1200 m and 1700 m a.s.l. Whereas
      lowland populations are panmictic across distances over 70 km, montane
      populations can be disjunct over 4 km, despite continuous forest cover. We
      suggest that the limited gene flow between populations of these two species of
      montane Ficus may be driven by environmental limitations on pollinator or seed
      dispersal in combination with local adaptation of Ficus populations. Such a
      mechanism may have wider implications for plant and pollinator speciation across
      long and continuously forested elevational gradients if generalist insect
      pollinators and vertebrate seed dispersers also form populations based on
      elevation.

PMID- 27868285
TI  - Review of chemotherapeutic approaches for operable and inoperable esophageal
      squamous cell carcinoma.
AB  - The predominant histological types of esophageal cancer are adenocarcinoma and
      squamous cell carcinoma. Since these two histological types present as different
      diseases in terms of their epidemiology, pathologenesis, and tumor biology,
      separate therapeutic approaches should be developed against each type. While
      surgical resection remains the dominant therapeutic intervention for patients
      with operable esophageal squamous cell carcinoma (ESCC), their high rates of
      tumor recurrence have prompted investigation of multimodality therapies that
      combine surgery with chemotherapy, radiotherapy, and chemoradiotherapy. In Japan,
      preoperative chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU)
      followed by radical esophagectomy has been accepted as the standard therapeutic
      approach for resactable clinical Stage II/III ESCC. Similarly, the CDDP and 5-FU
      regimen has been accepted as the first-line treatment for metastatic and
      unresectable ESCCs in Japan. Thus, in Japan chemotherapy is an indispensable
      component of therapy for both resectable and unresectable ESCCs. This review
      discusses the current knowledge, rationale, and available data regarding
      chemotherapy for resectable and unresectable ESCCs.

PMID- 27868286
TI  - A high number of stromal tumor-infiltrating lymphocytes is a favorable
      independent prognostic factor in M0 (stages I-III) esophageal squamous cell
      carcinoma.
AB  - Esophageal cancer is a highly invasive tumor with a poor prognosis. Lymphocytes
      play an important role in systemic immune responses, but their role in cancers
      varies depending on the specific tumor microenvironment. The aim of this study
      was to provide evidence for tumor-infiltrating lymphocytes (TILs) as a prognostic
      biomarker in esophageal squamous cell carcinoma. TIL analysis was retrospectively
      performed on full-face hematoxylin and eosin-stained sections from 127 patients.
      A majority (92.6%) of tumors had at least 10% stromal TILs (sTILs) (range, 10%
      90%), and 84.3% of cancers had at least 10% intraepithelial TILs (iTILs) (range,
      10%-40%). Multivariate analysis showed progressively better overall survival (P <
      0.001, hazard ratio = 0.968, 95% confidence interval 0.955-0.981) and disease
      free survival (P = 0.005, hazard ratio = 0.982, 95% confidence interval 0.970
      0.995) in patients with higher sTILs. Marginal increases in overall survival and
      disease-free survival were found in the higher iTILs cohort versus the lower
      iTILs cohort, but the difference was not significant. In conclusion, in addition
      to tumor stage increasing stromal lymphocytic infiltration is an independent
      prognostic factor for esophageal squamous cell carcinoma treated by radical
      resection.

PMID- 27868287
TI  - Development of a nomogram for the prediction of pathological complete response
      after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell
      carcinoma.
AB  - Nomograms incorporating multiple prognostic factors are useful for individualized
      estimation of survival in cancer patients. However, nomograms for the prediction
      of pathological complete response (pCR) after neoadjuvant chemoradiotherapy
      (nCRT) in patients with esophageal cancer are scarce. Here, we describe the
      development of a nomogram for predicting pCR after nCRT in patients with
      esophageal squamous cell carcinoma (ESCC). We retrospectively reviewed the
      records of 392 ESCC patients who underwent nCRT followed by esophagectomy.
      Seventy percent of the participants (n = 274) were randomly assigned to a
      training cohort, whereas the remaining 30% were included in a validation cohort
      (n = 118). Data from the training cohort were subjected to multivariate logistic
      regression analyses for selecting variables to be included in the nomogram. The
      performance of the resulting nomogram was internally and externally validated by
      calculating the bias-corrected concordance statistic (c-statistic) and the area
      under the receiver operating characteristics curve (AUROC) in the training and
      validation cohorts, respectively. After surgery, 25.77% of the study patients
      achieved pCR. The following variables were included in the nomogram: (i) age,
      (ii) pretreatment tumor length, (iii) history of head and neck cancer, (iv) post
      nCRT albumin levels, and (v) post-nCRT endoscopic findings coupled with
      endoscopic biopsy results. The bias-corrected c-statistic and AUROC of the
      internal and external validation sets were 0.77 and 0.747, respectively. Our
      nomogram showed a good performance for predicting pCR after nCRT in ESCC
      patients.

PMID- 27868289
TI  - Determinants of health-related quality of life in anti-MAG neuropathy: a cross
      sectional multicentre European study.
AB  - Our objective was to assess determinants of quality of life (QoL) in anti-myelin
      associated glycoprotein antibody (MAG) neuropathy. The SF-36 questionnaire was
      assessed in 55 patients, from Marseille, Angers (France) and Birmingham (UK).
      Routine clinical evaluations included Medical Research Council (MRC) sum score,
      inflammatory neuropathy cause and treatment (INCAT) sensory score, inflammatory
      Rasch-built overall disability score (I-RODS), ataxia score, Jamar grip
      dynamometry, timed 10-m walk, neuropathic pain symptom inventory (NPSI) score,
      and fatigue severity score (FSS). Physical component summary (PCS) and mental
      component summary (MCS) of the SF36 questionnaire were significantly lower than
      in reported normal subjects of both countries (p < 0.001). All SF-36 domains
      correlated with I-RODS, except MCS for which significance was, however,
      approached (p = 0.056). PCS correlated with MRC sum score, ataxia score, timed 10
      m walk, tremor, Jamar grip dynamometry, NPSI pain score, FSS and level of social
      support. MCS correlated exclusively with FSS and level of social support. In
      multivariate regression, PCS was associated independently with I-RODS (p < 0.001)
      and NPSI pain score (p = 0.011), whereas MCS was associated independently with
      FSS (p = 0.022). QoL is accurately predicted in anti-MAG neuropathy by the I-RODS
      and FSS, lending support to their use in clinical and research settings.
      Effective measures to improve QoL should include tremor and neuropathic pain
      treatment, fatigue management, and improved social support.

PMID- 27868290
TI  - Outcomes of definitive chemoradiation in patients with esophageal cancer.
AB  - The incidence of esophageal cancer has risen dramatically in the Western world.
      Although surgical resection of esophageal tumors is considered the cornerstone of
      curative approaches in localized esophageal cancer, approximately 40% of patients
      who undergo chemoradiation followed by surgery will experience a recurrence.
      Additionally, surgical resection is not a viable option for many patients with
      locally advanced unresectable disease, poor general condition or whose condition
      deteriorated following chemoradiation. Several investigators have, therefore,
      attempted to evaluate the outcomes of definitive chemoradiation in patients with
      localized or locally advanced esophageal cancer. The outcomes of concurrent
      chemoradiation remain a matter of debate given the heterogenous study design and
      treatment regimens used in recent trials. Understanding the clinical benefit of
      chemoradiation is essential prior to recommending it as an alternative to
      surgery. In our review, we present the most recent studies evaluating the role of
      chemoradiation to better define the clinical outcomes of patients with special
      attention to overall survival.

PMID- 27868288
TI  - P21, COX-2, and E-cadherin are potential prognostic factors for esophageal
      squamous cell carcinoma.
AB  - Much research effort has been devoted to identifying prognostic factors for
      esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no
      conclusive findings have been reached thus far. We hypothesized that certain
      molecules identified in previous studies might serve as useful prognostic markers
      for ESCC. Therefore, the aim of the current study was to validate the most
      relevant markers showing potential for ESCC prognosis in our prospective
      esophageal cancer database. A literature search was performed using the PubMed
      database for papers published between 1980 and 2015 using the following key
      words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature
      selection criteria were established to identify the most widely studied markers,
      and we further validated the selected markers in a cohort from our single-surgeon
      team, including 153 esophageal cancer patients treated from 2000 to 2010. A total
      of 1799 articles were identified, 82 of which met the selection criteria. Twelve
      markers were found to be the most widely studied, and the validation results
      indicated that only P21, COX-2, and E-cadherin were independent prognostic
      factors for ESCC patients in this series. The systemic review and cohort
      validation suggest that P21, COX-2, and E-cadherin are potential prognostic
      factors for ESCC, paving the way for more targeted prospective validation in the
      future.

PMID- 27868291
TI  - Tagging polymorphisms of methyl-CpG binding domain 4 and gastric cardiac
      adenocarcinoma risk in a Chinese population.
AB  - Potential effects of genetic factors on carcinogenesis of gastric cardiac
      adenocarcinoma (GCA) may exist. The present experiment specifically evaluated the
      genetic influence of single nucleotide in methyl-CpG binding domain 4 (MBD4) on
      GCA tumorigenesis. A case-control experiment based on hospital recruited 330 GCA
      patients and 608 non-cancer patients was carried out. We employed ligation
      detection reaction method to detect the genotypes. The results revealed that MBD4
      rs3138373, rs2005618, and rs3138355 mutations had no significant association with
      the risk of GCA. However, a lower risk of GCA presented in male patients who
      carried the MBD4 rs3138355 G>A polymorphic loci by the stratified analyses. In
      general, The MBD4 gene polymorphism could not influence GCA hereditary
      predisposition. Nevertheless, whether the finding learned from our experiment
      could apply to other ethnic groups will remain vague until future multicenter
      studies further test and verify our conclusions.

PMID- 27868292
TI  - Patterns of reflux in gastroesophageal reflux disease in pediatric population of
      New South Wales.
AB  - This study is to determine the association of ambulatory pH monitoring (24hr pH)
      with symptoms of gastroesophageal reflux and its other investigations. The
      clinical and epidemiological profiles of subjects referred for reflux disorders
      are also studied. Symptoms or group of symptoms, profiles and prior
      investigations of 1259 consecutive pediatric subjects (with 1332 24hr pH studies
      performed) referred for evaluation of reflux disorders between 1988 and 2012 were
      retrospectively studied. Chi-square or fisher exact test was used for hypothesis
      testing, student t-test for the comparison of means and the Wilcoxon rank-sum
      test for comparing medians of continuous variables. Gastroesophageal reflux
      disease (GERD), defined as reflux causing major symptoms and complications, was
      diagnosed in 57.5% subjects of the total sample. Forty-three percent were girls
      and 56.7% were boys. The most common age group was between 4 months and 2 years
      (51.2%). Vomiting (64.4%) and irritability (74%) were the most common symptoms
      with the neurological conditions (23.2%) being the most frequent underlying
      condition. The parameters used in 24hr pH were significantly higher in those
      diagnosed with GERD (P < 0.0001). The prevalence of GERD was found to be
      significantly higher when both gastrointestinal and respiratory symptoms were
      present (P = 0.008) at 66.4% than when compared with gastrointestinal (56.5%) and
      respiratory (52.2%) symptoms in isolation. Symptoms alone were not reliable in
      diagnosing GERD. Only 57.5% had GERD among patients referred for reflux
      disorders. 24hr pH is reliable and should be considered routine in reflux
      disorders, as it identifies patients with pathologic reflux and avoids a needless
      surgery.

PMID- 27868293
TI  - Clinical features of diffuse large B-cell lymphoma with polyploidy.
AB  - Polyploidy, defined as more than two sets of homologous chromosomes, is found in
      a variety of malignant tumors and is thought to be related to disease
      pathogenesis. However, there have been no studies that have investigated
      polyploidy in diffuse large B-cell lymphoma (DLBCL). Here we reviewed
      clinicopathological features of 16 cases of DLBCL with polypoidy, which was
      defined as DLBCL with either near-tetraploid or greater number of chromosomes as
      detected by the G-band method. The frequency of polyploid DLBCL was 2.9 %
      (16/544), including 15 near-tetraploid and one near-pentaploid case. CD5, CD30
      and EBER positive cases were 13 % (2/16), 13 % (2/16) and 6 % (1/16),
      respectively. Bcl2 positive cases were 75 % (12/16). The numbers of huge and
      multinucleated cells were higher in polyploid than in non-polyploid DLBCL (P =
      0.0029 and P < 0.0001, respectively). Clinical features of polyploid DLBCL
      included reduced infiltration of extranodal sites (2/15, 13 %) and major lymph
      node infiltration. Of seven cases that received chemotherapy, six responded to
      treatment and survived. Our results suggest that polyploid DLBCL represents a
      clinicopathologically characteristic group of DLBCL. This knowledge can be useful
      for informing more personalized and targeted management of DLBCL patients.

PMID- 27868294
TI  - Effect of dietary calcium level and source on mineral utilisation by piglets fed
      diets containing exogenous phytase.
AB  - Calcium and phosphorus are essential minerals, closely linked in digestive
      processes and metabolism. With widespread use of low P diets containing exogenous
      phytase, the optimal dietary Ca level was verified. The 40-day study evaluated
      the effects of Ca level (4, 7 and 10 g/kg diet) and Ca source (Ca from CaCO3 and
      from Lithothamnium calcareum) on mineral utilisation in 72 piglets (7.9 +/- 1.0
      kg BW) fed an exogenous phytase containing diet with 2.9 g digestible P/kg.
      Measured parameters were growth performance, stomach mineral solubility, bone
      breaking strength and urinary, serum and bone mineral concentration. The apparent
      total tract digestibility of minerals was also assessed in the two diets with 7 g
      Ca/kg, using 12 additional pigs. Regardless of Ca source, increasing dietary Ca
      impaired feed conversion ratio, increased urinary pH, increased serum and urinary
      Ca, decreased serum and urinary P, decreased serum Mg and increased urinary Mg,
      increased serum AP activity, decreased bone Mg increased bone Zn. Bone breaking
      strength was improved with 7 compared to 4 g Ca/kg. Compared to CaCO3 , Ca from
      Lithothamnium calcareum increased serum Mg and with, 10 g Ca/kg, it limited body
      weight gain. The dose response of Ca in a diet with 2.9 g digestible P/kg and
      including exogenous phytase indicated that: (i) a low dietary Ca was beneficial
      for piglet growth, but was limiting the metabolic use of P; (ii) a high dietary
      Ca level impaired P utilisation; (iii) the optimal P utilisation and bone
      breaking strength was obtained with a dietary Ca-to-digestible P ratio of 2.1 to
      2.4:1; (iv). Increasing dietary Ca reduced Mg utilisation, but not Zn status,
      when fed at adequate level. Finally, Ca from Lithothamnium calcareum had similar
      effects on Ca and P metabolism as CaCO3 , but impaired growth when fed at the
      highest inclusion level.

PMID- 27868295
TI  - Efficacy and safety of cisplatin-based versus nedaplatin-based regimens for the
      treatment of metastatic/recurrent and advanced esophageal squamous cell
      carcinoma: a systematic review and meta-analysis.
AB  - Cisplatin and nedaplatin show significant antitumor activity and have been widely
      used for esophageal squamous cell carcinoma (ESCC). However, it is still unclear
      whether the efficacy and safety of nedaplatin-based regimens are comparable to
      those of cisplatin-based regimens in patients with metastatic/recurrent or
      advanced ESCC. Therefore, we conducted a systematic review and meta-analysis to
      compare the efficacy and safety of these two regimens for the treatment of
      metastatic/recurrent and advanced ESCC. We systematically searched Pubmed, Web of
      Science, and the Cochrane Database, as well as abstracts presented at conferences
      (all up to January 2015), for randomized-controlled and nonrandomized clinical
      trials that compared cisplatin-based and nedaplatin-based regimens in patients
      with metastatic/recurrent or advanced ESCC. Data were extracted from the original
      studies by two independent reviewers. This meta-analysis was performed using
      Review Manager (RevMan) Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The
      Cochrane Collaboration, 2014) software. Ten eligible trials, including 598
      patients diagnosed with metastatic/recurrent or advanced ESCC, were included in
      our analysis. Our results demonstrated that the nedaplatin-based regimens were
      comparable to the cisplatin-based regimens in terms of overall survival (OS)
      (hazard ratio, HR: 1.22, 95% confidence interval, CI: 0.86-1.74, p = 0.26) and
      overall response rate (ORR) (risk ratio, RR: 0.92, 95% CI: 0.77-1.10, p = 0.37)
      and generated fewer grade 3 and 4 side effects including nausea (RR: 3.41, 95%
      CI: 1.67-6.96, p < 0.001) and vomiting (RR: 3.62, 95% CI: 1.77-7.40, p < 0.001)
      and fewer grade 1 and 2 adverse events including nausea (RR: 1.54, 95% CI: 1.23
      1.93, p < 0.001), vomiting (RR: 1.76, 95% CI: 1.76-2.30, p < 0.001), peripheral
      neuropathy (RR: 1.75, 95% CI: 1.08-2.84, p = 0.02) and renal dysfunction
      (creatinine) (RR: 3.28, 95% CI: 1.37-7.84, p = 0.008). This systematic review and
      meta-analysis indicated that the efficacy of nedaplatin-based regimens was
      comparable to that of cisplatin-based regimens for patients with
      metastatic/recurrent or advanced ESCC, and that nedaplatin-based regimens were
      associated with less toxicity and better tolerability. However, this study was a
      meta-analysis of previously released data; therefore, there is a potential
      publication bias and heterogeneity among the included trials. Future, well
      designed RCTs with large cohorts are warranted.

PMID- 27868296
TI  - Improving access to immunisation for migrants and refugees: recommendations from
      a stakeholder workshop.

PMID- 27868297
TI  - Making guidelines for economic evaluations relevant to public health in
      Australia.

PMID- 27868298
TI  - Changes to smoking habits and addiction following tobacco excise tax increases: a
      comparison of Maori, Pacific and New Zealand European smokers.
AB  - OBJECTIVE: To compare changes in smoking habit and psychological addiction in
      Maori/Pacific and NZ European smokers in response to two annual excise tax
      increases from 2012 to 2014. METHODS: Smokers from New Zealand cities completed
      questionnaires at three time points before and after two excise tax increases.
      RESULTS: There were no significant differences in cigarettes per day or
      psychological addiction at baseline, but a linear decline in both measures was
      observed in Maori/Pacific and NZ European smokers. Cigarettes per day reduced at
      a greater rate for Maori/Pacific than NZ European smokers but dependence did not.
      CONCLUSION: Results indicated that Maori/Pacific smokers' demand for cigarettes
      may be more price sensitive than NZ European smokers. Implications for Public
      Health: Tobacco excise tax may be particularly effective for Maori/Pacific
      smokers and may contribute to reductions in smoking-related health inequalities
      in NZ.

PMID- 27868299
TI  - Quantifying maternal incarceration: a whole-population linked data study of
      Western Australian children born 1985-2011.
AB  - OBJECTIVE: To measure the prevalence of children affected by maternal
      incarceration in Western Australia (WA). METHODS: Using linked administrative
      data we identified all children born in WA between 1985 and 2011, whose
      biological mother was imprisoned during their childhood. Data was obtained
      through the WA Data Linkage Branch from the Department of Corrective Services,
      Midwives Notifications System and Birth Registrations data collections.
      Descriptive characteristics of the children (n=9,352) and their mothers (n=3,827)
      are reported. Prevalence was measured in two-ways, the proportion of children
      ever affected in childhood and affected annually. RESULTS: Childhood prevalence
      of maternal incarceration was 26-times higher (95%CI 23.9-28.2) for Indigenous
      children born 1992-1996 with 18.8% Indigenous children and 0.7% non-Indigenous
      children affected while aged 0-17 years. On average 1,544 children were affected
      each year across 2003-2011, at rates of 2,929 per 100,000 Indigenous children and
      108 per 100,000 non-Indigenous children. CONCLUSIONS: The findings present the
      first census of children affected by maternal incarceration within an Australian
      State and identify a large disparity between Indigenous and non-Indigenous
      populations. Implications for public health: This study highlights the importance
      of formal consideration of children of women prisoners in the development of
      criminal justice policies and practices.

PMID- 27868300
TI  - Outcomes of using telehealth for the provision of healthcare to Aboriginal and
      Torres Strait Islander people: a systematic review.
AB  - OBJECTIVE: To examine reported outcomes of health services delivered by
      telehealth to Indigenous Australians. METHODS: Systematic review of the
      literature. Searches were conducted to identify articles that reported a
      telehealth service used to provide clinical services to Indigenous Australians.
      Articles were screened for inclusion using pre-defined criteria. Findings were
      synthesised narratively and reported using the preferred reporting items for
      systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: 14 articles,
      describing 11 distinct telehealth services, were selected based on the inclusion
      criteria. Authors of included studies report that telehealth has improved social
      and emotional wellbeing, clinical outcomes and access to health services for
      Indigenous Australians. Further, it has reduced travel and improved screening
      rates. Indigenous people report positive perceptions of their telehealth
      interaction. CONCLUSION: Telehealth is used to address poor accessibility to
      health services and for targeted screening programs for at risk populations.
      Reported outcomes from existing services demonstrate the potential of telehealth
      for health service delivery for Indigenous Australians. Confidence in the
      findings of this review is reduced by the predominance of descriptive studies and
      small sample sizes in many of the included articles. IMPLICATIONS: Telehealth
      models of care facilitated through partnerships between Aboriginal community
      controlled health services and public hospitals may improve both patient outcomes
      and access to specialist services for Indigenous people.

PMID- 27868301
TI  - Exploring MALDI-TOF MS approach for a rapid identification of Mycobacterium avium
      ssp. paratuberculosis field isolates.
AB  - AIMS: The aim of the study was to explore the suitability of matrix-assisted
      laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) for a
      rapid and correct identification of Mycobacterium avium ssp. paratuberculosis
      (MAP) field isolates. METHODS AND RESULTS: MALDI-TOF MS approach is becoming one
      of the most popular tests for the identification of intact bacterial cells which
      has been shown to be fast and reliable. For this purpose, 36 MAP field isolates
      were analysed through MALDI-TOF MS and the spectra compared with two different
      databases: one provided by the vendor of the system employed (Biotyper ver. 3.0;
      Bruker Daltonics) and a homemade database containing spectra from both
      tuberculous and nontuberculous Mycobacteria. Moreover, principal component
      analysis procedure was employed to confirm the ability of MALDI-TOF MS to
      discriminate between very closely related subspecies. Our results suggest MAP can
      be differentiated from other Mycobacterium species, both when the species are
      very close (M. intracellulare) and when belonging to different subspecies (M.
      avium ssp. avium and M. avium ssp. silvaticum). CONCLUSIONS: The procedure
      applied is fast, easy to perform, and achieves an earlier accurate species
      identification of MAP and nontuberculous Mycobacteria in comparison to other
      procedures. SIGNIFICANCE AND IMPACT OF THE STUDY: The gold standard test for the
      diagnosis of paratuberculosis is still isolation of MAP by cultural methods, but
      additional assays, such as qPCR and subculturing for determination of mycobactin
      dependency are required to confirm its identification. We have provided here
      evidence pertaining to the usefulness of MALDI-TOF MS approach for a rapid
      identification of this mycobacterium among other members of M. avium complex.

PMID- 27868303
TI  - Fat-free mass index predicts survival in patients with idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Detailed body composition, such as fat-free mass, has
      not been examined in idiopathic pulmonary fibrosis (IPF). We investigated whether
      the fat-free mass index (FFMI), an index of lean body mass, predicted survival.
      METHODS: Forty-four patients with IPF were enrolled in the study. Their body
      composition was assessed using direct segmental multi-frequency bioelectrical
      impedance analysis. The degree of correlation between variables of body
      composition and other variables such as forced vital capacity (FVC) and survival
      was examined. RESULTS: There was a significant positive correlation between FFMI
      and FVC, diffusion capacity of the lung for carbon monoxide (DLCO ) and 6-min
      walk distance, and a significant negative correlation with age. However, there
      was no significant correlation between FFMI and percentage predicted FVC or DLCO
      , with the degree of correlation being similar to that observed for BMI. The mean
      observation period in the survival analysis was 837.5 +/- 407.5 days. A
      univariate Cox proportional hazard model showed that several variables, but not
      BMI, were associated significantly with survival. FFMI (hazard ratio (HR): 0.64,
      95% CI: 0.43-0.94, P = 0.02) and percentage predicted FVC (HR: 0.96, 95% CI: 0.93
      0.99, P=0.008) were significant factors in a multivariate model. CONCLUSION: We
      conclude that FFMI is a significant independent predictor of survival in patients
      with IPF.

PMID- 27868302
TI  - Reduced DNA methylation of sphingosine-1 phosphate receptor 5 in alveolar
      macrophages in COPD: A potential link to failed efferocytosis.
AB  - BACKGROUND AND OBJECTIVE: We previously showed that alveolar macrophages from
      COPD patients are defective in their ability to phagocytose apoptotic cells
      ('efferocytosis') and that this defect is potentially linked to the sphingosine-1
      phosphate (S1P) system, in particular the sphingosine-1 phosphate receptor 5
      (S1PR5). In alveolar macrophages from COPD patients, S1PR5 mRNA expression levels
      increased and were correlated with both lung function and efferocytosis. However,
      it us unknown whether these changes are under epigenetic control via DNA
      methylation or whether DNA methylation directly modulates macrophage function.
      METHODS: Bisulfite sequencing was used to assess DNA methylation levels at CpG
      islands associated with genes encoding selected S1P system components, including
      sphingosine kinase 1 (SPHK1), S1PR1 and S1PR5, in alveolar macrophages from 20
      COPD patients, 7 healthy smokers and 10 healthy non/ex-smokers) by methyl
      quantitative real-time PCR (methyl qPCR). The effect of the DNA methyltransferase
      inhibitor, 5-azacytidine on the efferocytosis capacity of THP-1 macrophages was
      assessed using flow cytometry. RESULTS: Among the S1P system genes examined,
      S1PR5 was the single target that showed significant changes in DNA methylation
      between patient groups. Alveolar macrophages isolated from COPD patients showed
      lower methylation levels in the same region compared to macrophages from non/ex
      smokers. in vitro studies using THP-1 macrophages showed that DNA demethylation
      with 5-azacytidine increased the efferocytosis capacity and dose-dependently
      rescued the cells from the cigarette smoke-induced defect in efferocytosis.
      CONCLUSION: Macrophage function can be modulated epigenetically. Reduced
      methylation may underlie the increased expression of the S1PR5 gene in alveolar
      macrophages and associated defective efferocytosis in COPD.

PMID- 27868304
TI  - Individual, social and environmental factors and their association with weight in
      rural-dwelling women.
AB  - OBJECTIVE: Obesity is a major public health concern and women living in rural
      settings present a high-risk group. With contributing factors poorly explored, we
      evaluated their association with weight in rural Australian women. METHODS: Women
      aged 18-50 years of any body mass index (BMI) were recruited between October 2012
      and April 2013 as part of a larger, randomised controlled trial within 42 rural
      towns. Measured weight and height as well as self-reported measures of individual
      health, physical activity, dietary intake, self-management, social support and
      environmental perception were collected. Statistical analysis included linear
      regression for continuous variables as well as chi-squared and logistic
      regression for categorical variables with all results adjusted for clustering.
      RESULTS: 649 women with a mean baseline age and BMI of 39.6+/-6.7 years and
      28.8+/-6.9 kg/m2 respectively, were studied. Overall, 65% were overweight or
      obese and 60% overall reported recent weight gain. There was a high intention to
      self-manage weight, with 68% attempting to lose weight recently, compared to 20%
      of women reporting health professional engagement for weight management. Obese
      women reported increased weight gain, energy intake, sitting time and prevalence
      of pre-existing health conditions. There was an inverse relationship between
      increased weight and scores for self-management, social support and health
      environment perception. CONCLUSIONS: Many women in rural communities reported
      recent weight gain and were attempting to self-manage their weight with little
      external support. Implications for public health: Initiatives to prevent weight
      gain require a multifaceted approach, with self-management strategies and social
      support in tandem with building a positive local environmental perception.

PMID- 27868305
TI  - Growth, nutrient digestibility, ileal digesta viscosity, and energy
      metabolizability of growing turkeys fed diets containing malted sorghum sprouts
      supplemented with enzyme or yeast.
AB  - Growth, apparent nutrient digestibility, ileal digesta viscosity, and energy
      metabolizability of growing turkeys fed diets containing malted sorghum sprouts
      (MSP) supplemented with enzyme or yeast were investigated using 120, 28-day-old
      male turkeys. Six treatments were laid out in a 3 * 2 factorial arrangement of
      treatments with three dietary inclusion levels of MSP (0, 50, and 100 g/kg) and
      supplemented with 200 mg/kg yeast (Saccharomyces cerevisiae) or 200 mg/kg of a
      commercial enzyme. The experiment lasted for the starter (day 28-56) and grower
      phases (day 57-84) of the birds. Each treatment group consisted of 20 turkeys
      replicated four times with five birds each. Data were analysed using analysis of
      variance while polynomial contrast was used to determine the trends (linear and
      quadratic) of MSP inclusion levels. Irrespective of dietary supplementation with
      enzyme or yeast, final body weight (BW), total BW gain, and feed intake for
      turkey poults from day 29-56 was reduced (p < 0.05) with increasing inclusion
      level of MSP. Dietary supplementation with yeast resulted in increased (p < 0.05)
      feed intake while enzyme supplementation improved (p < 0.05) feed conversion
      ratio of the poults. Turkeys fed enzyme-supplemented MSP diets had higher (p <
      0.05) BW gain than their counterparts fed yeast-supplemented MSP diets. Apparent
      ash digestibility reduced linearly (p < 0.05) with increasing inclusion levels of
      MSP. Apparent metabolizable energy (AME) did not vary significantly (p > 0.05)
      with MSP inclusion levels. Enzyme supplementation reduced (p < 0.05) ileal
      viscosity but had no effect (p > 0.05) on AME. Inclusion of MSP resulted in poor
      growth performance. This confirms earlier studies that utilization of MSP by
      poultry is rather poor. Supplementation with enzyme or yeast did not lead to any
      appreciable improvement in performance of turkeys in this study.

PMID- 27868306
TI  - Sample size for clinical trials.

PMID- 27868307
TI  - Effects of eosinophilic oesophagitis on quality of life in an adult UK
      population: a case control study.
AB  - Eosinophilic oesophagitis (EoE) is a chronic immune-mediated esophageal disease,
      characterized by symptoms related to esophageal dysfunction and histologically by
      eosinophil predominant inflammation. Current evidence for an adverse impact on
      quality of life (QoL) is conflicting and there are no data from a UK population
      regarding QoL. We conducted a prospective cross-sectional observational study
      using the Short Form-36 Health Survey, Hospital Dysphagia/Odynophagia
      Questionnaire, and the EoE Adult Quality of Life Questionnaire to assess QoL and
      severity of dysphagia in EoE patients, compared to age and gender matched healthy
      control subjects. Data were also collected on comorbidity and medication use.
      Eighty-eight subjects were recruited (44 patients). Patients had higher rates of
      antihistamine and topical (swallowed) corticosteroid use. Physical QoL did not
      differ between patients and controls, although patients did report a
      statistically significant lower mental QoL, with small absolute magnitude of
      difference. Patients reported higher dysphagia scores and these were negatively
      correlated with both physical and mental QoL. Higher rates of dysphagia and
      medication use in patients may among other things account for lower mental QoL.
      However, a higher rate of dysphagia in patients is not associated with a reduced
      physical QoL. Our findings are of clinical value, particularly when a new
      diagnosis of EoE is made, as clinicians can reassure patients that their general
      physical health should not be greatly affected by the diagnosis. Moreover, it may
      also be useful for patients to be aware that EoE may have an impact on their
      mental health, but this effect is likely to be small. We therefore advocate
      education and reassurance in this respect for all patients at diagnosis.

PMID- 27868309
TI  - An examination of how alcohol brands use sport to engage consumers on social
      media.
AB  - INTRODUCTION AND AIMS: To examine how alcohol brands use sport in their
      communication activities on social media. Despite extensive research exploring
      alcohol advertising and sponsorship through sport, minimal attention has been
      given to digital platforms. DESIGN AND METHODS: This study undertakes a
      qualitative content analysis to examine the social media activity of alcohol
      brands sponsoring the three largest spectator sports in Australia: Australian
      rules football, rugby league and cricket. RESULTS: Four sport-related social
      media strategies are identified through which alcohol brands solicit interaction
      with consumers, often involving co-creation of content and social activation.
      These strategies act as 'calls to action' and through the association of sport
      and alcohol encourage consumers to engage in competition, collaboration,
      celebration and consumption. These strategies are further strengthened by
      communications which draw upon themes of identity and camaraderie to resonate
      with the consumer. DISCUSSION AND CONCLUSIONS: Sport-linked social media
      strategies utilised by alcohol brands extend beyond just promoting their product.
      They seek higher levels of engagement with the consumer to amplify and augment
      the connection between alcohol and the sport spectator experience. The discussion
      highlights the powerful combination of sport and social media as a mechanism by
      which these brands seek to interact with consumers and encourage them to both
      create and promote content to their social networks. These strategies allow
      alcohol brands to extend their marketing efforts in a manner which can elude
      alcohol codes and prove difficult for regulators to identify and control.
      [Westberg K, Stavros C, Smith ACT, Munro G, Argus K. An examination of how
      alcohol brands use sport to engage consumers on social media. Drug Alcohol Rev
      2018;37:28-35].

PMID- 27868310
TI  - The serotonergic anxiolytic buspirone attenuates circadian responses to light.

PMID- 27868308
TI  - 'Partnerships are crucial': an evaluation of the Aboriginal Family Birthing
      Program in South Australia.
AB  - OBJECTIVES: To evaluate implementation and outcomes of the Aboriginal Family
      Birthing Program (AFBP), which provides culturally competent antenatal,
      intrapartum and early postnatal care for Aboriginal families across South
      Australia (SA). METHODS: Analysis of births to Aboriginal women in SA 2010-2012;
      interviews with health professionals and AFBP clients. RESULTS: Around a third of
      all Aboriginal women giving birth in SA 2010-2012 (n=486) attended AFBP services.
      AFBP women were more likely to be more socially disadvantaged, have poorer
      pregnancy health and to have inadequate numbers of antenatal visits than
      Aboriginal women attending other services. Even with greater social disadvantage
      and higher clinical complexity, pregnancy outcomes were similar for AFBP and
      other Aboriginal women. Interviews with 107 health professionals (including 20
      Aboriginal Maternal and Infant Care (AMIC) workers) indicated differing levels of
      commitment to the model, with some lack of clarity about AMIC workers and
      midwives roles. Interviews with 20 AFBP clients showed they highly valued care
      from another Aboriginal woman. CONCLUSIONS: Despite challenges, the AFBP reaches
      out to women with the greatest need, providing culturally appropriate, effective
      care through partnerships. Implications for Public Health: Programs like the AFBP
      need to be expanded and supported to improve maternal and child health outcomes
      for Aboriginal families.

PMID- 27868311
TI  - TNF-alpha-induced IL-6 and MMP-9 expression in immortalized ameloblastoma cell
      line established by hTERT.
AB  - OBJECTIVE: Ameloblastoma (AM) shows locally invasive behaviour. However,
      biological investigations regarding regulation of gene expression associated with
      AM pathological features are difficult to perform, because AM cells can be
      passaged for a few generations due to senescence. We report a newly established
      immortalized AM cell line, AMB cells, by transfection with human telomerase
      reverse transcriptase (hTERT). Furthermore, we examined whether TNF-alpha
      modulates bone resorption-related genes, IL-6 and MMP-9 in cooperation with TGF
      beta or IFN-gamma. MATERIALS AND METHODS: Following transfection of an hTERT
      expression vector into AM cells using a non-viral method, the effects of
      cytokines on the expressions of IL-6 and MMP-9 mRNA were examined using real-time
      PCR. TNF-alpha-induced NF-kappaB activity was examined by western blotting and
      transcription factor assays. RESULTS: AMB cells continued to grow for more than
      100 population doublings. Stimulation with TNF-alpha increased IL-6 and MMP-9
      mRNA expressions, as well as NF-kappaB activation. Furthermore, TGF-beta and IFN
      gamma dramatically increased TNF-alpha-mediated expressions of MMP-9 and IL-6
      mRNA, respectively, while those responses were suppressed by NF-kappaB inhibitor.
      CONCLUSION: We established an immortalized AM cell line by hTERT transfection.
      TNF-alpha-mediated regulation of MMP-9 and IL-6 via NF-kappaB may play an
      important role in the pathological behaviour of AMs, such as bone resorption.

PMID- 27868312
TI  - Effect of chicken leptin recptor short hairpin RNA on expression of JAK2, STAT3,
      SOCS3 and CPT1 genes in chicken preadipocytes.
AB  - In this study, we detect depressive effect on leptin receptor (LEPR) by LEPR
      specific short hairpin RNA (shRNA) expression plasmids in chicken preadipocytes,
      and effect on messenger RNA (mRNA) expression levels of genes related to signal
      transduction, including JAK2, STAT3, SOCS3 as well as CPT1, which is associated
      with fatty acid metabolism. shRNA expression vectors targeting LEPR were
      constructed and transfected into chicken preadipocytes. The transfection
      efficiency was evaluated by fluorescence microscopy. Real-time PCR was used to
      detect its effect on mRNA expression levels of JAK2, STAT3, SOCS3 and CPT1.
      Results showed that LEPR mRNA was knocked down by 99% (P < 0.01) after
      transfection for 72 h. In the knockdown preadipocytes, the mRNA levels of JAK2
      and CPT1 were down-regulated by 47.56% (P < 0.01) and 42.26% (P < 0.05),
      respectively; while expression of STAT3 and SOCS3 increased 7.72-fold (P < 0.01),
      1.71-fold (P < 0.01), respectively. It is concluded that knockdown of LEPR
      influences mRNA expression of its down-stream genes, suggesting that chicken LEPR
      play a certain role in regulating genes in the complicated gene network of
      preadipocytes.

PMID- 27868313
TI  - Nutrient-dependent increased dendritic arborization of somatosensory neurons.
AB  - Suboptimal nutrition imposes developmental constraints on infant animals, which
      marshal adaptive responses to eventually become mature adults. Such responses are
      mounted at multiple levels from systemic to cellular. At the cellular level, the
      underlying mechanisms of cell proliferation control have been intensively
      studied. However, less is known about how growth of postmitotic and
      morphologically complex cells, such as neurons, is controlled by nutritional
      status. We address this question using Class I and Class IV dendritic
      arborization neurons in Drosophila larvae. Class IV neurons have been shown to
      sense nociceptive thermal, mechanical and light stimuli, whereas Class I neurons
      are proprioceptors. We reared larvae on diets with different protein and
      carbohydrate content throughout larval stages and examined how morphologies of
      Class I or Class IV neurons were affected. Dendritic arbors of Class IV neurons
      became more complex when larvae were reared on a low-yeast diet, which contains
      lower amounts of amino acids and other ingredients, compared to a high-yeast
      diet. In contrast, such low-yeast-dependent hyperarborization was not seen in
      Class I neurons. The physiological and metabolic implications of the
      hyperarborization phenotype are discussed in relation to a recent hypothesis that
      Class IV neurons sense protein-deficient stress and to our characterization of
      how the dietary yeast contents impacted larval metabolism.

PMID- 27868314
TI  - Experimental whole-stream warming alters community size structure.
AB  - How ecological communities respond to predicted increases in temperature will
      determine the extent to which Earth's biodiversity and ecosystem functioning can
      be maintained into a warmer future. Warming is predicted to alter the structure
      of natural communities, but robust tests of such predictions require appropriate
      large-scale manipulations of intact, natural habitat that is open to dispersal
      processes via exchange with regional species pools. Here, we report results of a
      two-year whole-stream warming experiment that shifted invertebrate assemblage
      structure via unanticipated mechanisms, while still conforming to community-level
      metabolic theory. While warming by 3.8  degrees C decreased invertebrate
      abundance in the experimental stream by 60% relative to a reference stream, total
      invertebrate biomass was unchanged. Associated shifts in invertebrate assemblage
      structure were driven by the arrival of new taxa and a higher proportion of
      large, warm-adapted species (i.e., snails and predatory dipterans) relative to
      small-bodied, cold-adapted taxa (e.g., chironomids and oligochaetes).
      Experimental warming consequently shifted assemblage size spectra in ways that
      were unexpected, but consistent with thermal optima of taxa in the regional
      species pool. Higher temperatures increased community-level energy demand, which
      was presumably satisfied by higher primary production after warming. Our
      experiment demonstrates how warming reassembles communities within the
      constraints of energy supply via regional exchange of species that differ in
      thermal physiological traits. Similar responses will likely mediate impacts of
      anthropogenic warming on biodiversity and ecosystem function across all
      ecological communities.

PMID- 27868315
TI  - Intraobserver Agreement on Histopathologic Evaluations of Core Breast Biopsies.
AB  - The number of performed core biopsies of the breast as diagnostic workup is
      increasing in many European countries. We measured the intraobserver variability
      in pathological assessment of breast core biopsies. Furthermore, we studied
      potential modifiers of agreement between the assessments. Two hundred and fifty
      six breast biopsies were evaluated twice in a blinded fashion by two
      pathologists. We calculated the observed and the chance-corrected (weighted)
      intraobserver agreement (kappa) using the B-categorization scheme (B1: normal or
      not interpretable, B2: benign, B3: benign but of uncertain biological potential,
      B4: suspicious of malignancy, B5: malignant). The observed agreement between the
      first and the second assessments were 0.80 (95% CI: 0.75-0.85) for pathologist 1
      and 0.81 (95% CI: 0.76-0.86) for pathologist 2. The chance-corrected agreements
      were 0.85 (95% CI: 0.80-0.89) and 0.81 (95% CI: 0.76-0.87), respectively. The
      most frequent disagreement was between B1 and B2 for pathologist 1 (N = 34 out of
      50 disagreements, 68%) and between B2 and B3 for pathologist 2 (N = 23 out of 48
      disagreements, 48%). Our study shows that the chance-corrected agreement between
      the histopathological evaluations of breast biopsies based on the B
      categorization scheme is almost perfect. The level of agreement is modified by
      biopsy technique and by the level of suspicion of the mammographic lesion.

PMID- 27868317
TI  - Comparative testing of disinfectant efficacy on planktonic bacteria and bacterial
      biofilms using a new assay based on kinetic analysis of metabolic activity.
AB  - AIMS: The aim of our study was to develop a new reproducible method for
      disinfectant efficacy testing on bacterial biofilms and to evaluate the efficacy
      of different disinfectants against biofilms. Clinical multidrug-resistant strains
      were chosen as test isolates to ensure practical relevance. METHODS AND RESULTS:
      We compared the standard qualitative suspension assay for disinfectant testing,
      which does not take into account biofilm formation, to the new biofilm viability
      assay that uses kinetic analysis of metabolic activity in biofilms after
      disinfectant exposure to evaluate disinfectant efficacy. In addition, the
      efficacy of four standard disinfectants to clinical isolates was tested using
      both methods. All tested disinfectants were effective against test isolates when
      in planktonic state using the standard qualitative suspension assay, while
      disinfectants were only weakly effective against bacteria in biofilms.
      CONCLUSIONS: Disinfectant efficacy testing on planktonic organisms ignores
      biofilms and overestimates disinfectant susceptibility of bacteria. However,
      biofilm forming, e.g. on medical devices or hospital surfaces, is the natural
      state of bacterial living and needs to be considered in disinfectant testing.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Although bacterial biofilms are the
      predominant manner of bacterial colonization, most standard procedures for
      antimicrobial susceptibility testing and efficacy testing of disinfectants are
      adapted for application to planktonic bacteria. To our knowledge, this is the
      first study to use a newly developed microplate-based biofilm test system that
      uses kinetic analysis of the metabolic activity in biofilms, after disinfectant
      exposure, to evaluate disinfectant efficacy. Our study shows that findings
      obtained from disinfectant efficacy testing on planktonic bacteria cannot be
      extrapolated to predict disinfectant efficacy on bacterial biofilms of clinically
      relevant multidrug-resistant organisms.

PMID- 27868318
TI  - Zika virus infection and biological treatment for reproductive medicine.
AB  - The recent Zika virus (ZIKV) epidemic is particularly challenging in the field of
      reproductive medicine as various biological tissues and byproducts, such as
      intravenous immunoglobulin G or cells are utilized during reproductive cycles,
      and an infected mother has an increased risk of having babies with fetal
      microcephaly and other congenital brain anomalies. In this review, current
      guidelines for prevention of sexual transmission of ZIKV, ZIKV testing, and
      tissue and blood product usages are summarized for physicians caring for those
      planning pregnancy or going through infertility treatment.

PMID- 27868316
TI  - Effect of organic and inorganic selenium supplementation on semen quality and
      blood enzymes in buffalo bulls.
AB  - The present study aimed to evaluate the effect of organic and inorganic selenium
      (Se) supplementation on semen quality and blood serum profiles of buffalo bulls.
      Nine mature buffalo bulls were divided into three groups: control (non
      supplemented); organic Se (10 mg Sel-Plex(r)/head twice weekly) and inorganic Se
      (10 mg sodium selenite/head twice weekly). Semen was collected twice a week for 3
      months during Se supplementation. Semen properties were evaluated from fresh
      ejaculate. Moreover, fructose concentration, aspartate and alanine transaminase
      (AST and ALT) activities, total protein and total cholesterol were assayed in
      seminal plasma. Additionally AST, ALT, testosterone and Se levels were determined
      in the blood serum. Results showed that Se supplementation significantly (P <
      0.05) influences the semen parameters during 3 months of treatment. Organic Se
      significantly (P < 0.05) increased the percentage of viable sperms compared to
      inorganic Se and the control group. Fructose concentration was significantly
      higher (P < 0.05) in the seminal plasma of organic Se-treated bulls. Serum
      testosterone and Se concentrations were significantly (P < 0.05) increased in the
      Se supplemented groups than the control group. In conclusion, Se supplementation
      improved the parameters of buffalo bull semen and more precisely, organic Se was
      more effective for the improvement of semen quality and some blood components
      than inorganic Se.

PMID- 27868319
TI  - Infection assays in Arabidopsis reveal candidate effectors from the poplar rust
      fungus that promote susceptibility to bacteria and oomycete pathogens.
AB  - Fungi of the Pucciniales order cause rust diseases which, altogether, affect
      thousands of plant species worldwide and pose a major threat to several crops.
      How rust effectors-virulence proteins delivered into infected tissues to modulate
      host functions-contribute to pathogen virulence remains poorly understood.
      Melampsora larici-populina is a devastating and widespread rust pathogen of
      poplar, and its genome encodes 1184 identified small secreted proteins that could
      potentially act as effectors. Here, following specific criteria, we selected 16
      candidate effector proteins and characterized their virulence activities and
      subcellular localizations in the leaf cells of Arabidopsis thaliana. Infection
      assays using bacterial (Pseudomonas syringae) and oomycete (Hyaloperonospora
      arabidopsidis) pathogens revealed subsets of candidate effectors that enhanced or
      decreased pathogen leaf colonization. Confocal imaging of green fluorescent
      protein-tagged candidate effectors constitutively expressed in stable transgenic
      plants revealed that some protein fusions specifically accumulate in nuclei,
      chloroplasts, plasmodesmata and punctate cytosolic structures. Altogether, our
      analysis suggests that rust fungal candidate effectors target distinct cellular
      components in host cells to promote parasitic growth.

PMID- 27868322
TI  - Spotlights on our sister journals: Chem. Eur. J. 48/2016.

PMID- 27868320
TI  - Predictors of rehospitalization among older adults: Results of the CRIME Study.
AB  - AIM: To assess the predictors of readmission among older adults hospitalized in
      acute care wards. METHODS: A prospective cohort study was carried out among 921
      hospitalized older adults participating in the CRiteria to Assess Appropriate
      Medication Use among Elderly Complex Patients (CRIME) project. The primary
      outcome of the study was rehospitalization within 1 year after discharge from
      acute care hospitals. We assessed the participants with a questionnaire including
      350 items about demographic, social and clinical characteristics. We analyzed all
      factors at discharge that could be considered predictors of readmission. RESULTS:
      The mean age of the participants was 81.2 years (SD 7.4 years), and 509 were
      women (55.3%). Overall, 280 of 921 patients (30.4%) were rehospitalized during
      the 1-year follow up of the study. Patients with a Mini-Mental State Examination
      score equal to or higher than 24 had a higher probability of rehospitalization,
      as compared with those who performed lower than 24 (OR 1.76, 95% CI 1.04-2.83).
      In addition, heart failure (OR 1.77, 95% CI 1.14-2.24), the number of falls
      during 1-year follow up (OR 1.15, 95% CI 1.05-1.28) and the number of drugs
      during first hospitalization (OR 1.15, 95% CI 1.01-1.07) were significantly
      associated with rehospitalization, whereas no significant association was shown
      for age, sex and walking speed for minimum size (OR 1.15, 95% CI 0.99-2.00).
      CONCLUSIONS: Predictors of readmission in older people are an intact cognitive
      status; the presence of a geriatric condition, such as heart failure and falls;
      and a high number of drugs during first hospitalization. Further studies are
      required to assess the impact of home care for avoiding readmission in patients
      with an intact cognitive status, and supporting and treating patients with
      dementia. Geriatr Gerontol Int 2017; 17: 1588-1592.

PMID- 27868321
TI  - Dementia-related adverse events in PARADIGM-HF and other trials in heart failure
      with reduced ejection fraction.
AB  - AIMS: Inhibition of neprilysin, an enzyme degrading natriuretic and other
      vasoactive peptides, is beneficial in heart failure with reduced ejection
      fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor
      neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is
      also one of many enzymes clearing amyloid-beta peptides from the brain, there is
      a theoretical concern about the long-term effects of sacubitril/valsartan on
      cognition. Therefore, we have examined dementia-related adverse effects (AEs) in
      PARADIGM-HF and placed these findings in the context of other recently conducted
      HFrEF trials. METHODS AND RESULTS: In PARADIGM-HF, patients with symptomatic
      HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg
      b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the
      Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA
      Queries (SMQs) with 'broad' and 'narrow' preferred terms related to dementia. In
      PARADIGM-HF, 8399 patients aged 18-96 years were randomized and followed for a
      median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27
      dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on
      sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33
      1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95%
      CI 0.75-1.37), respectively. The rates of dementia-related AEs in both treatment
      groups in PARADIGM-HF were similar to those in three other recent trials in
      HFrEF. CONCLUSION: We found no evidence that sacubitril/valsartan, compared with
      enalapril, increased dementia-related AEs, although longer follow-up may be
      necessary to detect such a signal and more sensitive tools are needed to detect
      lesser degrees of cognitive impairment. Further studies to address this question
      are warranted.

PMID- 27868323
TI  - Light-Induced Porphyrin-Based Spectroscopic Ruler for Nanometer Distance
      Measurements.
AB  - We present a novel pulsed electron paramagnetic resonance (EPR) spectroscopic
      ruler to test the performance of a recently developed spin-labeling method based
      on the photoexcited triplet state (S=1). Four-pulse electron double resonance
      (PELDOR) experiments are carried out on a series of helical peptides, labeled at
      the N-terminal end with the porphyrin moiety, which can be excited to the triplet
      state, and with the nitroxide at various sequence positions, spanning distances
      in the range 1.8-8 nm. The PELDOR traces provide accurate distance measurements
      for all the ruler series, showing deep envelope modulations at frequencies
      varying in a progressive way according to the increasing distance between the
      spin labels. The upper limit is evaluated and found to be around 8 nm. The PELDOR
      derived distances are in excellent agreement with theoretical predictions. We
      demonstrate that high sensitivity is acquired using the triplet state as a spin
      label by comparison with Cu(II)-porphyrin analogues. The new labeling approach
      has a high potential for measuring nanometer distances in more complex biological
      systems due to the properties of the porphyrin triplet state.

PMID- 27868324
TI  - To measure or not to measure direct oral anticoagulants before surgery or
      invasive procedures: reply.

PMID- 27868325
TI  - Novel EED mutation in patient with Weaver syndrome.
AB  - Weaver syndrome is a rare condition characterized by overgrowth, macrocephaly,
      accelerated osseous maturation, variable intellectual disability, and
      characteristic facial features. Pathogenic variants in EZH2, a histone
      methyltransferase, have previously been identified as a cause of Weaver syndrome.
      However, the underlying molecular cause in many patients remains unknown. We
      report a patient with a clinical diagnosis of Weaver syndrome whose exome was
      initially non-diagnostic. Reports in the medical literature of EED associated
      overgrowth prompted re-analysis of the patient's original exome data. The patient
      was found to have a likely pathogenic variant in EED. These findings support that
      Weaver syndrome is a disorder with locus heterogeneity and can be due to
      pathogenic variants in either EZH2 or EED. This case highlights the utility of
      exome sequencing as a clinical diagnostic tool for novel gene discovery as well
      as the importance of re-examination of exome data as new information about gene
      disease associations becomes available. (c) 2016 Wiley Periodicals, Inc.

PMID- 27868326
TI  - Quantitative trait locus mapping reveals complex genetic architecture of
      quantitative virulence in the wheat pathogen Zymoseptoria tritici.
AB  - We conducted a comprehensive analysis of virulence in the fungal wheat pathogen
      Zymoseptoria tritici using quantitative trait locus (QTL) mapping. High
      throughput phenotyping based on automated image analysis allowed the measurement
      of pathogen virulence on a scale and with a precision that was not previously
      possible. Across two mapping populations encompassing more than 520 progeny, 540
      710 pycnidia were counted and their sizes and grey values were measured. A
      significant correlation was found between pycnidia size and both spore size and
      number. Precise measurements of percentage leaf area covered by lesions provided
      a quantitative measure of host damage. Combining these large and accurate
      phenotypic datasets with a dense panel of restriction site-associated DNA
      sequencing (RADseq) genetic markers enabled us to genetically dissect pathogen
      virulence into components related to host damage and those related to pathogen
      reproduction. We showed that different components of virulence can be under
      separate genetic control. Large- and small-effect QTLs were identified for all
      traits, with some QTLs specific to mapping populations, cultivars and traits and
      other QTLs shared among traits within the same mapping population. We associated
      the presence of four accessory chromosomes with small, but significant, increases
      in several virulence traits, providing the first evidence for a meaningful
      function associated with accessory chromosomes in this organism. A large-effect
      QTL involved in host specialization was identified on chromosome 7, leading to
      the identification of candidate genes having a large effect on virulence.

PMID- 27868328
TI  - Long-term outcome of the adjustable transobturator male system (ATOMS): results
      of a European multicentre study.
AB  - OBJECTIVE: To evaluate the long-term effectiveness and safety of the adjustable
      transobturator male system (ATOMS(r) , Agency for Medical Innovations A.M.I.,
      Feldkirch, Austria) in a European-wide multicentre setting. PATIENTS AND METHODS:
      In all, 287 men with stress urinary incontinence (SUI) were treated with the
      ATOMS device between June 2009 and March 2016. Continence parameters (daily pad
      test/pad use), urodynamics (maximum urinary flow rate, voiding volume, residual
      urine), and pain/quality of life (QoL) ratings (visual analogue scale/Leeds
      Assessment of Neuropathic Symptoms and Signs, International Consultation on
      Incontinence Questionnaire-Short Form [ICIQ-SF]/Patient Global Impression of
      Improvement [PGI-I]) were compared preoperatively and after intermediate (12
      months) as well as after individual maximum follow-up. Overall success rate, dry
      rate (<10 mL/day and 0-1 pad/day), device durability, treatment failure, and
      device complications were recorded. Nonparametric tests were used for statistical
      analyses. RESULTS: After a median (interquartile range [IQR]) follow-up of 31 (10
      54) months and a median (IQR) of 3 (2-4) adjustments, the overall success rate
      was 90% (258 men) and the dry rate was 64% (184). Daily pad test and pad use
      decreased from a median of 400 mL/day and 4 pads/day to a median of 18 mL/day and
      1 pad/day (both P < 0.001), concomitantly QoL ratings significantly improved and
      changed to a high level of satisfaction (PGI-I 4 to 2, ICIQ-SF 17 to 5; both P <
      0.001). The UI results at 12 months were comparable to those at final follow-up.
      Chronic pain and intraoperative complications did not occur. Most of the
      postoperative complications were Clavien-Dindo grade I-III (no grade IV or V). At
      present, 231 (80%) of all the ATOMS devices are still functioning; 56 (20%) were
      removed, the most common reason being local titanium intolerance (41%) and
      leak/dysfunction (30%). The operating time and continence outcome varied between
      port generations. In this regard the latest port generation (silicone-covered
      scrotal port) was superior to its predecessors. Primary implantation (P = 0.002),
      good physical health (P = 0.001), and no history of radiotherapy (P < 0.001) were
      prognostic factors for beneficial treatment outcome. CONCLUSION: The ATOMS device
      is safe and shows high treatment efficacy and patient satisfaction in the largest
      cohort study to date. The latest generation, with its pre-attached silicone
      covered scrotal port, is superior to its predecessors. Significantly better
      results were achieved with primary implantation and in those without a history of
      radiotherapy.

PMID- 27868329
TI  - Audible clicking on blinking: an adverse effect of topical prostaglandin analogue
      medication.

PMID- 27868330
TI  - Structural and functional analysis of cyclophilin PpiB mutants supports an in
      vivo function not limited to prolyl isomerization activity.
AB  - Escherichia coli cyclophilin PpiB is a peptidyl-prolyl cis/trans isomerase
      (PPIase, EC: 5.2.1.8), involved in the negative modulation of various bacterial
      processes, such as swimming and swarming motility and biofilm formation ability.
      In this study, we show that PpiB possesses also a chaperone function as it can
      prevent the thermal denaturation of citrate synthase even with essentially
      eliminated PPIase activity. We demonstrate, using active site mutations, that the
      PPIase activity of PpiB is required in all processes, except for the negative
      effect on swimming, indicating a possible isomerase-independent function.
      Additionally, we show that the reduced PPIase activity of PpiB does not prevent
      the association with all prey proteins tested and that the PPIase active site is
      not involved necessarily in each association. We also used a random mutagenesis
      approach, to identify amino acid residues apart from the catalytic site, which
      are necessary for PpiB function. The combination of enzymatic studies concerning
      the PPIase and chaperone activities of each mutant protein, with structural
      analyses based on 3D models, provided further insights into the effects of the
      mutations on the function of PpiB and showed the importance of structural
      features in addition to the catalytic site, for its in vivo role.

PMID- 27868327
TI  - Communication and patient participation influencing patient recall of treatment
      discussions.
AB  - CONTEXT: Patient recall of treatment information is a key variable towards
      chronic disease (CD) management. It is unclear what communication and patient
      participation characteristics predict recall. OBJECTIVES: To assess what aspects
      of doctor-patient communication predict patient recall of medication information.
      To describe lifestyle treatment recall, in CD primary care patients. DESIGN:
      Observational study within a RCT. SETTING & PARTICIPANTS: Community-based primary
      care (PC) practices. Family physicians (n=18): practicing >5 years, with a CD
      patient caseload. Patients (n=159): >40 years old, English speaking, computer
      literate, off-target hypertension, type II diabetes and/or dyslipidaemia. MAIN
      VARIABLES: Patient characteristics: age, education, number of CDs. Information
      characteristics: length of encounter, medication status, medication class.
      Communication variables: socio-emotional utterances, physician dominance and
      communication control scores and PACE (ask, check and express) utterances,
      measured by RIAS. Number of medication themes, dialogue and initiative measured
      by MEDICODE. MAIN OUTCOME MEASURES: Recall of CD, lifestyle treatment and
      medication information. RESULTS: Frequency of lifestyle discussions varied by
      topic. Patients recalled 43% (alcohol), 52% (diet) to 70% (exercise) of
      discussions. Two and a half of six possible medication themes were broached per
      medication discussion. Less than one was recalled. Discussing more themes,
      greater dialogue and patient initiative were significant predictors of improved
      medication information recall. DISCUSSION: Critical treatment information is
      infrequently exchanged. Active patient engagement and explicit conversations
      about medications are associated with improved treatment information recall in
      off-target CD patients followed in PC. CONCLUSION: Providers cannot take for
      granted that long-term off-target CD patients recall information. They need to
      encourage patient participation to improve recall of treatment information.

PMID- 27868331
TI  - Patient resilience in the fracture orthopaedic rehabilitation geriatric
      environment.
AB  - OBJECTIVE: To explore the relationship between resilience and rehabilitation
      outcomes in older orthopaedic patients. METHODS: Geriatric rehabilitation
      patients admitted to a general metropolitan hospital following a fracture were
      interviewed face-to-face. Their resilience was assessed using the Connor-Davidson
      Resilience Scale (CD-RISC), and rehabilitation outcomes were assessed according
      to functional independence measure (FIM) gain, length of stay, discharge
      destination and mortality rate. RESULTS: A total of 29 patient interviews were
      used in data analysis. Resilience scores varied from 49-92, with an average of
      73, representing overall high resilience compared to general population samples.
      Resilience scores as measured by the CD-RISC did not correlate with functional
      improvements during rehabilitation postfracture. CONCLUSION: Further studies,
      including patients with a broader range of resilience scores, particularly at the
      lower end of the spectrum, are required to explore the relationship between
      resilience and rehabilitation outcomes in greater depth.

PMID- 27868332
TI  - The transcriptional responses of cultured wound cells to the excretions and
      secretions of medicinal Lucilia sericata larvae.
AB  - Maggots, through their excretions and secretions (ES), promote wound healing by
      removing necrotic tissue, counter bacterial infection, and activate wound
      associated cells. We investigated the effects of a physiological dose of maggot
      ES on four wound-associated cell types in vitro with Affymetrix gene expression
      arrays; keratinocytes, endothelial cells, fibroblasts, and monocytes.
      Keratinocytes showed the fewest (n = 5; p < 0.05, fold-change +/-2) and smallest
      fold-changes (up to 2.32*) in gene expression and conversely THP1 monocytes had
      the most (n = 233) and greatest magnitude (up to 44.3*). There were no genes that
      were altered in all four cell-lines. Gene pathway analysis identified an
      enrichment of immune response pathways in three of the treated cell-lines.
      Analyses by quantitative RT-PCR found many genes dynamically expressed in ES dose
      dependent manner during the three day treatments. Phenotype analyses, however,
      found no effects of ES on cell viability, proliferation, migration and
      angiogenesis. ES was 100* less potent at triggering IL-8 secretion than
      fibroblasts treated with purified bacterial lipopolysaccharide (LPS; in
      equivalent amounts to that found in ES; ~40 EU/ml). Furthermore, co-treatment
      with LPS and ES decreased the LPS-alone triggered IL-8 secretion by 13%. Although
      ES had no direct effect on wound cell phenotypes it did partially reduce the
      immune response to bacterial LPS exposure. These observations were consistent
      with the profile of transcriptional responses that were dominated by modulation
      of immune response genes. Maggot therapy may therefore improve wound healing
      through the secondary effects of these gene changes in the wound cells.

PMID- 27868333
TI  - To measure or not to measure direct oral anticoagulants before surgery or
      invasive procedures: comment.

PMID- 27868334
TI  - Consensus on the standardization of terminology in thrombotic thrombocytopenic
      purpura and related thrombotic microangiopathies.
AB  - : Essentials An international collaboration provides a consensus for clinical
      definitions. This concerns thrombotic microangiopathies and thrombotic
      thrombocytopenic purpura (TTP). The consensus defines diagnosis, disease
      monitoring and response to treatment. Requirements for ADAMTS-13 are given.
      SUMMARY: Background Thrombotic thrombocytopenic purpura (TTP) and hemolytic
      uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic
      microangiopathy (TMA) is a broad pathophysiologic process that leads to
      microangiopathic hemolytic anemia and thrombocytopenia, and involves capillary
      and small-vessel platelet aggregates. The most common cause is disseminated
      intravascular coagulation, which may be differentiated by abnormal coagulation.
      Clinically, a number of conditions present with microangiopathic hemolytic anemia
      and thrombocytopenia, including cancer, infection, transplantation, drug use,
      autoimmune disease, and pre-eclampsia and hemolysis, elevated liver enzymes and
      low platelet count syndrome in pregnancy. Despite overlapping clinical
      presentations, TTP and HUS have distinct pathophysiologies and treatment
      pathways. Objectives To present a consensus document from an International
      Working Group on TTP and associated thrombotic microangiopathies (TMAs). Methods
      The International Working Group has proposed definitions and terminology based on
      published information and consensus-based recommendations. Conclusion The
      consensus aims to aid clinical decisions, but also future studies and trials,
      utilizing standardized definitions. It presents a classification of the causes of
      TMA, and criteria for clinical response, remission and relapse of congenital and
      immune-mediated TTP.

PMID- 27868335
TI  - The Elongator complex-associated protein DRL1 plays a positive role in immune
      responses against necrotrophic fungal pathogens in Arabidopsis.
AB  - DEFORMED ROOT AND LEAVES1 (DRL1) is an Arabidopsis homologue of the yeast TOXIN
      TARGET4 (TOT4)/KILLER TOXIN-INSENSITIVE12 (KTI12) protein that is physically
      associated with the RNA polymerase II-interacting protein complex named
      Elongator. Mutations in DRL1 and Elongator lead to similar morphological and
      molecular phenotypes, suggesting that DRL1 and Elongator may functionally overlap
      in Arabidopsis. We have shown previously that Elongator plays an important role
      in both salicylic acid (SA)- and jasmonic acid (JA)/ethylene (ET)-mediated
      defence responses. Here, we tested whether DRL1 also plays a similar role as
      Elongator in plant immune responses. Our results show that, although DRL1
      partially contributes to SA-induced cytotoxicity, it does not play a significant
      role in SA-mediated expression of PATHOGENESIS-RELATED genes and resistance to
      the virulent bacterial pathogen Pseudomonas syringae pv. maculicola ES4326. In
      contrast, DRL1 is required for JA/ET- and necrotrophic fungal pathogen Botrytis
      cinerea-induced defence gene expression and for resistance to B. cinerea and
      Alternaria brassicicola. Furthermore, unlike the TOT4/KTI12 gene which, when
      overexpressed in yeast, confers zymocin resistance, a phenotype of the tot4/kti12
      mutant, overexpression of DRL1 does not change B. cinerea-induced defence gene
      expression and resistance to this pathogen. Finally, DRL1 contains an N-terminal
      P-loop and a C-terminal calmodulin (CaM)-binding domain and is a CaM-binding
      protein. We demonstrate that both the P-loop and the CaM-binding domain are
      essential for the function of DRL1 in B. cinerea-induced expression of PDF1.2 and
      ORA59, and in resistance to B. cinerea, suggesting that the function of DRL1 in
      plant immunity may be regulated by ATP/GTP and CaM binding.

PMID- 27868336
TI  - Vascular imaging for hemodialysis vascular access planning.
AB  - INTRODUCTION: Central venous catheters (CVC) increase risks associated with
      hemodialysis (HD), but may be necessary until an arteriovenous fistula (AVF) or
      graft (AVG) is achieved. The impact of vascular imaging on achievement of working
      AVF and AVG has not been firmly established. METHODS: Retrospective cohort of
      patients initiating HD with CVC in 2010-2011, classified by exposure to
      venography or Doppler vein mapping, and followed through December 31, 2012.
      Standard and time-dependent Cox models were used to determine hazard ratios (HRs)
      of death, working AVF, and any AVF or AVG. Logistic regression was used to assess
      the association of preoperative imaging with successful AVF or AVG among 18,883
      individuals who had surgery. Models were adjusted for clinical and demographic
      factors. FINDINGS: Among 33,918 patients followed for a median of 404 days, 39.1%
      had imaging and 55.7% had surgery. Working AVF or AVG were achieved in 40.6%;
      46.2% died. Compared to nonimaged patients, imaged patients were more likely to
      achieve working AVF (HR = 1.45 [95% confidence interval [CI] 1.36, 1.55], P <
      0.001]), any AVF or AVG (HR = 1.63 [1.58, 1.69], P > 0.001), and less likely to
      die (HR = 0.88 [0.83-0.94], P < 0.001). Among patients who had surgery, the odds
      ratio for any successful AVF or AVG was 1.09 (1.02-1.16, P = 0.008). DISCUSSION:
      Fewer than half of patients who initiated HD with a CVC had vascular imaging.
      Imaged patients were more likely to have vascular surgery and had increased
      achievement of working AV fistulas and grafts. Outcomes of surgery were similar
      in patients who did and did not have imaging.

PMID- 27868338
TI  - Incomplete Timothy syndrome secondary to a mosaic mutation of the CACNA1C gene
      diagnosed using next-generation sequencing.
AB  - Autosomal dominant genetic diseases can occur de novo and in the form of somatic
      mosaicism, which can give rise to a less severe phenotype, and make diagnosis
      more difficult given the sensitivity limits of the methods used. We report the
      case of female child with a history of surgery for syndactyly of the hands and
      feet, who was admitted at 6 years of age to a pediatric intensive care unit
      following cardiac arrest. The electrocardiogram (ECG) showed a long QT interval
      that on occasions reached 500 ms. Despite the absence of facial dysmorphism and
      the presence of normal psychomotor development, a diagnosis of Timothy syndrome
      was made given the association of syndactyly and the ECG features. Sanger
      sequencing of the CACNA1C gene, followed by sequencing of the genes KCNQ1, KCNH2,
      KCNE1, KCNE2, were negative. The subsequent analysis of a panel of genes
      responsible for hereditary cardiac rhythm disorders using Haloplex technology
      revealed a recurrent mosaic p.Gly406Arg missense mutation of the CACNA1C gene in
      18% of the cells. This mosaicism can explain the negative Sanger analysis and the
      less complete phenotype in this patient. Given the other cases in the literature,
      mosaic mutations in Timothy syndrome appear more common than previously thought.
      This case demonstrates the importance of using next-generation sequencing to
      identify mosaic mutations when the clinical picture supports a specific mutation
      that is not identified using conventional testing. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27868337
TI  - Enhanced uptake of blood coagulation factor VIII containing immune complexes by
      antigen presenting cells.
AB  - : Essentials Anti-factor (F) VIII antibody formation is a major complication in
      the treatment of hemophilia A. We investigated uptake of FVIII and FVIII immune
      complex by bone marrow derived dendritic cells. Immune complex formation
      increased uptake of FVIII 3-4 fold in a Fcgamma receptor dependent manner. FVIII
      immune complex binding to Fcgamma receptors may modulate immune tolerance
      induction. SUMMARY: Background A major complication in the treatment of
      hemophilia A is the development of inhibitory antibodies targeting coagulation
      factor VIII (FVIII). Eradication of these inhibitors can be established by immune
      tolerance induction (ITI), which consists of daily administration of high dosages
      of FVIII. FVIII immune complexes (FVIII-IC) could be formed following FVIII
      infusion in patients with pre-existing anti-FVIII antibodies. Objectives Here we
      studied endocytosis of FVIII-IC by bone marrow-derived dendritic cells (BMDCs).
      Methods BMDCs were pulsed with FVIII/FVIII-IC and uptake was assessed by flow
      cytometry and confocal imaging. Results BMDCs were able to efficiently
      internalize FVIII-IC in a dose-dependent manner, 3-4-fold more efficiently when
      compared with equimolar concentrations of non-complexed FVIII. Uptake of FVIII
      IC, but not FVIII alone, could be inhibited with anti-Fcgamma receptor (FcgammaR)
      antibody 2.4G2, indicating functional involvement of FcgammaR. No internalization
      of FVIII-IC was observed in BMDCs lacking FcgammaRI, FcgammaRIIb, FcgammaRIII and
      FcgammaRIV. Genetic ablation of FcgammaRIIb, FcgammaRIII or FcgammaRIV
      individually did not affect the ability of anti-FVIII IgG to promote the uptake
      of FVIII. BMDCs lacking FcgammaRI showed lower FVIII-IC uptake levels when
      compared with other single FcgammaR null BMDCs. Expression of the inhibitory
      FcgammaRIIb alone was sufficient to internalize FVIII-IC more efficiently than
      FVIII. Conclusions FcgammaR are critical in the internalization of FVIII-IC by
      BMDCs and multiple FcgammaR can contribute independently to this process. Our
      findings provide a basis for future studies to address whether the outcome of ITI
      is dependent on the interplay between FVIII-IC and inhibitory and activating
      FcgammaR.

PMID- 27868340
TI  - Dental attendance patterns among older people: a retrospective review of records
      in public and private dental care in Sweden.
AB  - OBJECTIVES: Nowadays, older people retain their natural teeth more frequently and
      so are at increased risk of oral disease. At the same time, discontinued contacts
      with dental services prevent access to preventive care and increase the risk of
      undetected disease. This study aims to evaluate how often older people
      discontinue regular dental visits and to establish the reasons. METHODS: This
      study is a retrospective review of records of patients aged >=75 years from seven
      Swedish clinics, three in the public dental service (PuDS) and four in the
      private (PrDS). All patients were examined in 2010, and their dental attendance
      records from 2010 to 2014 studied. Data included gender, dental insurance system,
      last performed planned examination, emergency visits, registrations in the recall
      system, cause of discontinued care and number of teeth and implants. RESULTS: In
      total, 993 records were studied, 303 in PuDS and 690 in PrDS. In both groups, 10%
      of patients had no complete dental examinations between 2010 and 2014 after
      baseline examination in 2010. One-quarter were not registered in the recall
      system after their last examinations, and this was more common in PrDS than PuDS.
      In many cases, no reason for discontinued regular visits were described in the
      records. The mean number of natural teeth was 19.0 in both groups, but there were
      more implants in the PrDS group. CONCLUSIONS: A large proportion of the
      participants risked losing regular contact with dental services. Dental services
      appeared to lack strategies for maintaining regular dental care for elderly
      patients.

PMID- 27868341
TI  - A single-arm trial indirect comparison investigation: a proof-of-concept method
      to predict venous leg ulcer healing time for a new acellular synthetic matrix
      matched to standard care control.
AB  - To compare data on time to healing from two separate cohorts: one treated with a
      new acellular synthetic matrix plus standard care (SC) and one matched from four
      large UK pragmatic, randomised controlled trials [venous leg ulcer (VLU) evidence
      network]. We introduce a new proof-of-concept strategy to a VLU clinical evidence
      network, propensity score matching and sensitivity analysis to predict the
      feasibility of the new acellular synthetic matrix plus SC for success in future
      randomised, controlled clinical trials. Prospective data on chronic VLUs from a
      safety and effectiveness study on an acellular synthetic matrix conducted in one
      wound centre in the UK (17 patients) and three wound centres in Australia (36
      patients) were compared retrospectively to propensity score-matched data from
      patients with comparable leg ulcer disease aetiology, age, baseline ulcer area,
      ulcer duration, multi-layer compression bandaging and majority of care completed
      in specialist wound centres (average of 1 visit per week), with the outcome
      measures at comparable follow-up periods from patients enrolled in four
      prospective, multicentre, pragmatic, randomised studies of venous ulcers in the
      UK (the comparison group; VLU evidence network). Analysis using Kaplan-Meier
      survival curves showed a mean healing time of 73.1 days for ASM plus SC (ASM)
      treated ulcers in comparison with 83.5 days for comparison group ulcers treated
      with SC alone (Log rank test, chi2 5.779, P = 0.016) within 12 weeks. Sensitivity
      analysis indicates that an unobserved covariate would have to change the odds of
      healing for SC by a factor of 1.1 to impact the baseline results. Results from
      this study predict a significant effect on healing time when using a new ASM as
      an adjunct to SC in the treatment of non-healing venous ulcers in the UK, but
      results are sensitive to unobserved covariates that may be important in healing
      time comparison.

PMID- 27868342
TI  - Food and beverage price discounts to improve health in remote Aboriginal
      communities: mixed method evaluation of a natural experiment.
AB  - OBJECTIVE: Retrospectively evaluate food price discounts in remote Aboriginal
      community stores. METHODS: Four price discount strategies of 10% were designed in
      2010, aiming to influence grocery, fruit, vegetables and diet soft-drink sales.
      This natural experiment across a group of stores was evaluated using an
      explanatory, sequential mixed method design through analysis of store point-of
      sale, document, observation and interview data. The outcome was measured by
      change in: 1) percentage of grocery sales to total food and beverage; 2) fruit
      and vegetable sales; and 3) diet soft-drink sales. Qualitative data enabled the
      interpretation of outcomes through understanding perceived success and benefits,
      and enablers and barriers to implementation. RESULTS: Eighteen community stores
      and 54 informants participated. While targeted price discounts were considered
      important to improving health, no discernible effect was evident, due to
      inadequate design and communication of discount promotion, and probably
      inadequate magnitude of discount. CONCLUSIONS: Strategy impact on food and
      beverage sales was limited by promotion and magnitude of discount. Implication
      for Public Health: This study demonstrates key factors and commitment required to
      design, communicate, implement and monitor strategies to improve health in this
      challenging remote retail context. Evaluation of natural experiments can
      contribute evidence to policy-making.

PMID- 27868339
TI  - FasL and the NKG2D receptor are required for the secretion of the Tag7/PGRP-S
      Hsp70 complex by the cytotoxic CD8+ lymphocytes.
AB  - Tag7 (PGRP-S or PGLYRP1), while possessing an antimicrobial activity, also
      exhibits an antitumor effect when in complex with the major heat shock protein
      Hsp70. The cytotoxic Tag7-Hsp70 complex is secreted by lymphocytes after
      interaction with the HLA-negative tumors. Previously, we have shown that IL-2
      induces formation of the CD4+ and CD8+ cytotoxic subpopulations of human
      lymphocytes, which kill tumor cells through the FasL-Fas interaction. Here, we
      show that only the CD8+ T cells are able to secrete the Tag7-Hsp70 complex. For
      its secretion the same proteins on the surface of the lymphocytes and target
      cells, which are involved in the contact lysis, are necessary as well. The
      interaction of Fas receptor with FasL leads to an activation of the Tag7-Hsp70
      complex in the lymphocyte membrane fraction, and here FasL acts as a receptor
      that induces intracellular signaling in lymphocytes. An interaction of the MicA
      stress ligand with the NKG2D receptor is necessary for the release of this
      cytotoxic complex. It is possible, that CD8+ T lymphocytes interacting with a
      target cell can both carry out the contact killing of these cells and to secrete
      the cytotoxic factor. (c) 2016 IUBMB Life, 69(1):30-36, 2017.

PMID- 27868343
TI  - Effectiveness of ramelteon for residual sleep disturbances (hypersomnia) in a
      patient with premenstrual dysphoric disorder.

PMID- 27868344
TI  - Further evidence that variants in PPP1CB cause a rasopathy similar to Noonan
      syndrome with loose anagen hair.

PMID- 27868346
TI  - Older people's description of factors that facilitate and impede regular dental
      care - a qualitative interview study.
AB  - OBJECTIVES: The aim of this study was to achieve an understanding of older
      people's view of the benefits of regular dental care and investigate factors that
      facilitate and impede regular dental care. METHODS: A qualitative research method
      was used. To gain a deeper understanding of the elderly people's views,
      individual interviews were conducted. Fifteen respondents, eleven women and four
      men aged between 65 and 95, participated, all recruited from senior social
      centres. All interviews were tape-recorded and transcribed verbatim, and the
      content analysis method was then used. Meaning units were identified and
      condensed into codes which were labelled and grouped into categories and
      subcategories. RESULTS: Findings were grouped into three categories: experiences
      of dental care, obstacles and facilitators to dental care and about oral health
      and responsibility. The elderly had experience of both regular and irregular
      dental care. Obstacles to visiting dental services included high costs and
      complicated dental insurance, other practical obstacles, lack of confidence in
      dentistry and seeing no benefits of dental care at their age. Views of the
      importance of oral health varied, and some people thought poor teeth were
      shameful. Some expressed that oral health was your own responsibility, while
      others thought that oral health was the responsibility of the dental services.
      CONCLUSIONS: Several factors which hamper regular dental care have been
      identified, and taken together, these obstacles often became unsurmountable.
      However, individuals taking their own responsibility for their dental status and
      dental services making certain adaptations, both encourage people to seek regular
      dental care.

PMID- 27868345
TI  - ConoSurf: Open-source 3D scanning system based on a conoscopic holography device
      for acquiring surgical surfaces.
AB  - BACKGROUND: A difficulty in computer-assisted interventions is acquiring the
      patient's anatomy intraoperatively. Standard modalities have several limitations:
      low image quality (ultrasound), radiation exposure (computed tomography) or high
      costs (magnetic resonance imaging). An alternative approach uses a tracked
      pointer; however, the pointer causes tissue deformation and requires sterilizing.
      Recent proposals, utilizing a tracked conoscopic holography device, have shown
      promising results without the previously mentioned drawbacks. METHODS: We have
      developed an open-source software system that enables real-time surface scanning
      using a conoscopic holography device and a wide variety of tracking systems,
      integrated into pre-existing and well-supported software solutions. RESULTS: The
      mean target registration error of point measurements was 1.46 mm. For a quick
      guidance scan, surface reconstruction improved the surface registration error
      compared with point-set registration. CONCLUSIONS: We have presented a system
      enabling real-time surface scanning using a tracked conoscopic holography device.
      Results show that it can be useful for acquiring the patient's anatomy during
      surgery.

PMID- 27868347
TI  - Identification of extreme motor phenotypes in Huntington's disease.
AB  - The manifestation of motor signs in Huntington's disease (HD) has a well-known
      inverse relationship with HTT CAG repeat length, but the prediction is far from
      perfect. The probability of finding disease modifiers is enhanced in individuals
      with extreme HD phenotypes. We aimed to identify extreme HD motor phenotypes
      conditional on CAG and age, such as patients with very early or very late onset
      of motor manifestation. Retrospective data were available from 1,218 healthy
      controls and 9,743 HD participants with CAG repeats >=40, and a total of about
      30,000 visits. Boundaries (2.5% and 97.5% quantiles) for extreme motor phenotypes
      (UHDRS total motor score (TMS) and motor age-at-onset) were estimated using
      quantile regression for longitudinal data. More than 15% of HD participants had
      an extreme TMS phenotype for at least one visit. In contrast, only about 4% of
      participants were consistent TMS extremes at two or more visits. Data from
      healthy controls revealed an upper cut-off of 13 for the TMS representing the
      extreme of motor ratings for a normal aging population. In HD, boundaries of
      motor age-at-onset based on diagnostic confidence or derived from the TMS data
      cut-off in controls were similar. In summary, a UHDRS TMS of more than 13 in an
      individual carrying the HD mutation indicates a high likelihood of motor
      manifestations of HD irrespective of CAG repeat length or age. The identification
      of motor phenotype extremes can be useful in the search for disease modifiers,
      for example, genetic or environmental such as medication. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27868349
TI  - Cognitive Analysis of Educational Games: The Number Game.
AB  - We analyze the cognitive strategies underlying performance in the Number task, a
      Math game that requires both arithmetic fluency and mathematical creativity. In
      this game all elements in a set of numbers (for instance, 2, 5, 9) have to be
      used precisely once to create a target number (for instance, 27) with basic
      arithmetic operations (solution: [5-2] * 9). We argue that some instances of this
      game are NP complete, by showing its relation to the well-known Partition
      problem. We propose heuristics based on the distinction in forward and backward
      reasoning. The Number Game is part of Math Garden, a popular online educational
      platform for practicing and monitoring math skills using innovations in
      computerized adaptive testing. These educational games generate enormous amounts
      of rich data on children's cognitive development. We found converging evidence
      for the use of forward proximity heuristics in the data of Math Garden,
      consisting of more than 20 million answers to 1,700 items. Item difficulties and
      the structure of correct answers were analyzed.

PMID- 27868348
TI  - Theory that explains an Aboriginal perspective of learning to understand and
      manage diabetes.
AB  - OBJECTIVE: To use grounded theory and participatory research methodology to
      explain how Aboriginal people learn to understand and manage type 2 diabetes.
      METHODS: Aboriginal people with diabetes were invited to participate in one of
      five focus groups (n=25, male=12, female=13). Focus groups and education sessions
      were conducted by Aboriginal members of the research team. Focus groups were
      audio recorded and transcribed, with coding and first level analysis undertaken
      by all members of the research team. RESULTS: Participants described colonisation
      and dislocation from Country and family members' experiences with diabetes as
      significant historical influences which, in conjunction with the model of care
      experienced and the type of interaction with health services, shaped how they
      came to understand and manage their diabetes. CONCLUSIONS: Patient experience of
      a model of care alone is not what influences understanding and management of
      diabetes in Aboriginal people. Implications for Public Health: Health service
      improvements should focus on understanding past experiences of Aboriginal
      patients, improving interactions with health services and supporting holistic
      family centred models of care. Focusing on just the model of care in absence of
      other improvements is unlikely to deliver health benefits to Aboriginal people.

PMID- 27868350
TI  - An elderly Jervell and Lange-Nielsen patient heterozygous compound for two new
      KCNQ1 mutations.
AB  - We present the case of a 66-year-old female with early onset deafness and
      seizures, who was diagnosed with epilepsy at the age of 2 years. She received
      antiepileptic drugs and was free of syncope episodes for 32 years. After a
      syncope at the age of 34, the ECG was characteristic of long-QT syndrome and was
      treated with antiarrhythmic drugs. Sequencing of the KCNQ1 gene identified two
      novel KCNQ1 variants interpreted to be pathogenic, and the patient was finally
      diagnosed with Jervell and Lange-Nielsen syndrome. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27868351
TI  - Essential elements of the nursing practice environment in nursing homes:
      Psychometric evaluation.
AB  - AIMS AND OBJECTIVES: To develop and psychometrically test the Essentials of
      Magnetism II in nursing homes. BACKGROUND: Increasing numbers and complex needs
      of older people in nursing homes strain the nursing workforce. Fewer adequately
      trained staff and increased care complexity raise concerns about declining
      quality. Nurses' practice environment has been reported to affect quality of care
      and productivity. The Essentials of Magnetism II (c) measures processes and
      relationships of practice environments that contribute to productivity and
      quality of care and can therefore be useful in identifying processes requiring
      change to pursue excellent practice environments. However, this instrument was
      not explicitly evaluated for its use in nursing home settings so far. DESIGN: In
      a preparatory phase, a cross-sectional survey study focused on face validity of
      the essentials of magnetism in nursing homes. A second cross-sectional survey
      design was then used to further test the instrument's validity and reliability.
      METHODS: Psychometric testing included evaluation of content and construct
      validity, and reliability. Nurses (N = 456) working at 44 units of three nursing
      homes were included. RESULTS: Respondent acceptance, relevance and clarity were
      adequate. Five of the eight subscales and 54 of the 58 items did meet preset
      psychometric criteria. CONCLUSIONS: All essentials of magnetism are considered
      relevant for nursing homes. The subscales Adequacy of Staffing, Clinically
      Competent Peers, Patient Centered Culture, Autonomy and Nurse Manager Support can
      be used in nursing homes without problems. The other subscales cannot be directly
      applied to this setting. IMPLICATIONS FOR PRACTICE: The valid subscales of the
      Essentials of Magnetism II instrument can be used to design excellent nursing
      practice environments that support nurses' delivery of care. Before using the
      entire instrument, however, the other subscales have to be improved.

PMID- 27868352
TI  - Hospital admissions in the Hunter Region from trees and other falling objects,
      2008-2012.
AB  - OBJECTIVE: To assess the impact on hospital admissions produced by trees and
      other falling objects, to examine these accidents' circumstances, and to
      investigate the degree of support provided by the data for tree-related accident
      prevention. METHODS: Admissions to emergency departments in the Hunter Region for
      the period 2008-2012 allocated the International Classification of Disease 10
      code W20 (struck by falling object) were analysed. RESULTS: Of 620 admissions,
      125 files were incorrectly coded leaving an eligible sample of 495 W20
      admissions. Males made up 79.4% of admissions. Where recorded, the commonest
      accident locations were workplaces (63.2%) and homes (31.5%). Trees/branches
      caused only 24 (4.8%) of such accidents with an age-adjusted admission rate of
      0.28 per 10,000 people compared with 6.84 per 10,000 for all falling objects
      combined. Most tree-related admissions (at least 62.5%) occurred to persons
      actively interacting with the tree. Being male (p=0.04) and living in an outer
      regional area (p=0.001) increased the incidence of tree injuries. CONCLUSIONS:
      Hospital admissions caused by falling objects especially trees are uncommon.
      Implications for public health: It is difficult to justify any major health
      promotion expenditure to reduce tree-related accidents, given their especial
      rarity. Any funds allocated should focus on preventing falling object injuries in
      workplaces and homes.

PMID- 27868353
TI  - Separation of four flavonol glycosides from Solanum rostratum Dunal using aqueous
      two-phase flotation followed by preparative high-performance liquid
      chromatography.
AB  - Aqueous two-phase flotation followed by preparative high-performance liquid
      chromatography was used to separate four flavonol glycosides from Solanum
      rostratum Dunal. In the aqueous two-phase flotation section, the effects of
      sublation solvent, solution pH, (NH4 )2 SO4 concentration in aqueous solution,
      cosolvent, N2 flow rate, flotation time, and volumes of the polyethylene glycol
      phase on the recovery were investigated in detail, and the optimal conditions
      were selected: 50 wt% polyethylene glycol 1000 ethanol solvent as the flotation
      solvent, pH 4, 350 g/L of (NH4 )2 SO4 concentration in aqueous phase, 40 mL/min
      of N2 flow rate, 30 min of flotation time, 10.0 mL of flotation solvent volume,
      and two times. After aqueous two-phase flotation concentration, the flotation
      products were purified by preparative high-performance liquid chromatography. The
      purities of the final products A and B were 98.1 and 99.0%. Product B was the
      mixture of three compounds based on the analysis of high-performance liquid
      chromatography at the temperature of 10 degrees C, while product A was hyperoside
      after the identification by nuclear magnetic resonance. Astragalin, 3'-O
      methylquercetin 3-O-beta-d-galactopyranoside, and 3'-O-methylquercetin 3-O-beta-d
      glucopyranoside were obtained with the purity of 93.8, 97.1, and 99.2%,
      respectively, after the further separation of product B using preparative high
      performance liquid chromatography.

PMID- 27868355
TI  - Oral health status of six-year-old children in Qatar: findings from the national
      oral health survey.
AB  - INTRODUCTION: Oral health has a significant impact on physical, social and mental
      well-being of an individual. Qatar, like the rest of the world, is experiencing
      higher prevalence of oral health-related problems. OBJECTIVES: To examine the
      oral health status and extent of preventive and curative needs among six-year-old
      school children in Qatar by key demographic indicators. METHODS: Secondary data
      analysis of 1124 six-year-old private and government primary school children from
      the 2011 Qatar National Oral Health Survey was performed. Dental caries lesions
      status of primary dentition was assessed according to the WHO criteria.
      Descriptive statistics were carried out, and comparison among groups was executed
      by running t statistics. Logistic regression was performed to interpret the
      impact of various predictors. RESULTS: Overall, 71.4% children presented with
      dental caries lesions with a higher prevalence among girls versus boys (73.8%
      versus 68.9%). The mean overall dmft was recorded as 4.2 with +/-4.2 SD. Qatari
      children had 3.8 time odds of having dental caries lesions compared with non
      Qatari children (P < 0.001). Overall, 18.9% of children showed signs of poor
      periodontal health. Odds of having more periodontal disease were significant in
      Qatari boys (OR = 3.1 CI = 2.0, 4.7, P < 0.001) compared to non-Qatari boys. On
      average, 3.6 teeth per student were in need of any treatment. CONCLUSION: This
      study indicated that only 28.6% of children aged six were free from caries
      lesions. The results urge to further strengthen the strategies and to improve
      oral hygiene by various evidence-based interventions.

PMID- 27868354
TI  - High incidence of BSCL2 intragenic recombinational mutation in Peruvian type 2
      Berardinelli-Seip syndrome.
AB  - Congenital generalized lipodystrophy (CGL) is a genetically heterogeneous group
      of disorders characterized by the absence of functional adipose tissue. We
      identified two pedigrees with CGL in the community of the Mestizo tribe in the
      northern region of Peru. Five cases, ranging from 15 months to 7 years of age,
      presented with generalized lipodystrophy, muscular prominence, mild intellectual
      disability, and a striking aged appearance. Sequencing of the BSCL2 gene, known
      to be mutated in type 2 CGL (CGL2; Berardinelli-Seip syndrome), revealed a
      homozygous deletion of exon 3 in all five patients examined, suggesting the
      presence of a founder mutation. This intragenic deletion appeared to be mediated
      by recombination between Alu sequences in introns 2 and 3. CGL2 in this
      population is likely underdiagnosed and undertreated because of its geographical,
      socio-economic, and cultural isolation.(c) 2016 Wiley Periodicals, Inc.

PMID- 27868356
TI  - The impact of the Dementia ABC educational programme on competence in person
      centred dementia care and job satisfaction of care staff.
AB  - AIM AND OBJECTIVES: The objective of the study was to evaluate the impact of the
      Dementia ABC educational programme on the participants' competence in person
      centred care and on their level of job satisfaction. BACKGROUND: The development
      of person-centred care for people with dementia is highly recommended, and staff
      training that enhances such an approach may positively influence job satisfaction
      and the possibility of recruiting and retaining competent care staff. DESIGN: The
      study is a longitudinal survey, following participants over a period of 24 months
      with a 6-month follow-up after completion of the programme. METHODS: A total of
      1,795 participants from 90 municipalities in Norway are included, and 580 from 52
      municipalities completed all measurements. The person-centred care assessment
      tool (P-CAT) is used to evaluate person-centredness. The psychosocial workplace
      environment and job satisfaction questionnaire is used to investigate job
      satisfaction. Measurements are made at baseline, and after 12, 24 and 30 months.
      RESULTS: A statistically significant increase in the mean P-CAT subscore of
      person-centred practice and the P-CAT total score is found at 12, 24 and 30
      months compared to baseline. A statistically significant decrease in scores in
      the P-CAT subscore for organisational support is found at all points of
      measurement compared to baseline. Statistically significant increases in
      satisfaction with workload, personal and professional development, demands
      balanced with qualifications and variation in job tasks as elements of job
      satisfaction are reported. CONCLUSION: The evaluation of the Dementia ABC
      educational programme identifies statistically significant increases in scores of
      person-centredness and job satisfaction, indicating that the training has a
      positive impact. IMPLICATIONS FOR PRACTICE: The results indicate that a
      multicomponent training programme including written material, multidisciplinary
      reflection groups and workshops has a positive impact on the development of
      person-centred care practice and the job satisfaction of care staff.

PMID- 27868357
TI  - An Unusual Magnetic Resonance Imaging of a Giant Cystic Volume of Tubular Adenoma
      of the Breast.

PMID- 27868358
TI  - Resolving microsatellite genotype ambiguity in populations of allopolyploid and
      diploidized autopolyploid organisms using negative correlations between allelic
      variables.
AB  - A major limitation in the analysis of genetic marker data from polyploid
      organisms is non-Mendelian segregation, particularly when a single marker yields
      allelic signals from multiple, independently segregating loci (isoloci). However,
      with markers such as microsatellites that detect more than two alleles, it is
      sometimes possible to deduce which alleles belong to which isoloci. Here, we
      describe a novel mathematical property of codominant marker data when it is
      recoded as binary (presence/absence) allelic variables: under random mating in an
      infinite population, two allelic variables will be negatively correlated if they
      belong to the same locus, but uncorrelated if they belong to different loci. We
      present an algorithm to take advantage of this mathematical property, sorting
      alleles into isoloci based on correlations, then refining the allele assignments
      after checking for consistency with individual genotypes. We demonstrate the
      utility of our method on simulated data, as well as a real microsatellite data
      set from a natural population of octoploid white sturgeon (Acipenser
      transmontanus). Our methodology is implemented in the R package polysat version
      1.6.

PMID- 27868359
TI  - Linagliptin improves endothelial function in patients with type 2 diabetes: A
      randomized study of linagliptin effectiveness on endothelial function.
AB  - AIMS/INTRODUCTION: The present multicenter, prospective, controlled, open and
      randomized three-arm parallel study was designed to compare the effects of
      linagliptin with those of metformin on endothelial function. MATERIALS AND
      METHODS: Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin
      A1c >=6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day
      (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and
      metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add-on
      group, n = 29) and treated for 16 weeks. Vascular endothelial function was
      evaluated by flow-mediated dilation. The primary end-point was changes in flow
      mediated dilation at 16 weeks relative to baseline. RESULTS: Linagliptin
      significantly improved flow-mediated dilation from baseline (4.9 +/- 2.7%) to 16
      weeks (6.3 +/- 2.7%, P < 0.05), whereas the other groups did not show any
      changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and
      linagliptin add-on groups compared with the control (6.6 +/- 0.6%, 6.5 +/- 0.5%
      and 7.0 +/- 0.6%, respectively). Single and multiple regression analyses showed
      that apolipoprotein B correlated significantly with change in flow-mediated
      dilation, and apolipoprotein B was decreased only in the linagliptin add-on group
      (-6.0 +/- 11.3 mg/dL, P < 0.01). CONCLUSIONS: Linagliptin for 16 weeks improved
      endothelial function with a modest improvement in glycemic control. This effect
      was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has
      a protective role on endothelial function in patients with type 2 diabetes with
      moderate hyperglycemia.

PMID- 27868362
TI  - Testing Sleep Consolidation in Skill Learning: A Field Study Using an Online
      Game.
AB  - Using an observational sample of players of a simple online game (n > 1.2
      million), we are able to trace the development of skill in that game. Information
      on playing time, and player location, allows us to estimate time of day during
      which practice took place. We compare those whose breaks in practice probably
      contained a night's sleep and those whose breaks in practice probably did not
      contain a night's sleep. Our analysis confirms experimental evidence showing a
      benefit of spacing for skill learning, but it fails to find any additional
      benefit of sleeping during a break from practice. We discuss reasons why the well
      established phenomenon of sleep consolidation might not manifest in an
      observational study of skill development. We put the spacing effect into the
      context of the other known influences on skill learning: improvement with
      practice, and individual differences in initial performance. Analysis of
      performance data from games allows experimental results to be demonstrated
      outside of the lab and for experimental phenomenon to be put in the context of
      the performance of the whole task.

PMID- 27868361
TI  - Synthesis of Peptidoglycan Fragments from Enterococcus faecalis with Fmoc
      Strategy for Glycan Elongation.
AB  - Peptidoglycan (PGN) is an essential structural component of the bacterial cell
      wall conferring cell shape, which can be recognized by host-recognition proteins
      and receptors as well as bacterial surface proteins. In this work, the PGN
      partial structures from Enterococcus faecalis that contain a tetrasaccharide and
      an octasaccharide with a unique heptapeptide were synthesized via an Fmoc
      strategy for elongation of the glycan chains. Namely, a 4'-O-Fmoc-protected
      disaccharide was utilized as the key intermediate in this efficient synthetic
      pathway for preparing various PGN fragments. Both the tetrasaccharide and
      octasaccharide with the unique heptapeptide were successfully synthesized for the
      first time.

PMID- 27868363
TI  - The long-term productivity impacts of all cause premature mortality in Australia.
AB  - OBJECTIVE: To estimate the long-term productivity impacts of all-cause premature
      mortality in Australia by age, sex and cause of death. METHODS: Using a human
      capital approach, a model was developed to estimate both the working years and
      present value of lifetime income (PVLI) lost due to premature deaths that
      occurred in 2003. Outcomes were modelled on individual level data to the year
      2030. A discount rate of 3% was applied and results are presented in 2015
      Australian dollars. RESULTS: Premature deaths occurring in 2003 accounted for
      about 284,000 working years lost and $13.8 billion in PVLI lost when modelled to
      2030. Deaths from cancer and cardiovascular disease accounted for more than half
      the total PVLI impact. Injuries and mental disorders were associated with the
      highest average PVLI loss per death. CONCLUSIONS: The productivity-related
      impacts of premature mortality are substantial. This study provides an assessment
      of relative impact of these costs across specific age, sex and cause of death
      categories. IMPLICATIONS: Policies and interventions that prevent premature
      mortality would improve both health and economic outcomes. An awareness of the
      productivity costs associated with all-cause mortality may assist decision makers
      in identifying population and disease subgroups where cost-effective health care
      investment can achieve the greatest economic gains to society.

PMID- 27868360
TI  - Global transcriptome responses including small RNAs during mixed-species
      interactions with methicillin-resistant Staphylococcus aureus and Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa and Staphylococcus aureus mixed-species biofilm infections
      are more resilient to biocide attacks compared to their single-species
      counterparts. Therefore, this study used an in vitro model recapitulating
      bacterial burdens seen in in vivo infections to investigate the interactions of
      P. aeruginosa and S. aureus in biofilms. RNA sequencing (RNA-seq) was utilized to
      identify the entire genomic response, both open reading frames (ORFs) and small
      RNAs (sRNAs), of each species. Using competitive indexes, transposon mutants
      validated uncharacterized PA1595 of P. aeruginosa and Panton-Valentine leukocidin
      ORFs of S. aureus are required for competitive success. Assessing spent media on
      biofilm development determined that the effects of these ORFs are not solely
      mediated by mechanisms of secretion. Unlike PA1595, leukocidin (lukS-PV) mutants
      of S. aureus lack a competitive advantage through contact-mediated mechanisms
      demonstrated by cross-hatch assays. RNA-seq results suggested that during
      planktonic mixed-species growth there is a robust genomic response or active
      combat from both pathogens until a state of equilibrium is reached during the
      maturation of a biofilm. In mixed-species biofilms, P. aeruginosa differentially
      expressed only 0.3% of its genome, with most ORFs necessary for growth and
      biofilm development, whereas S. aureus modulated approximately 5% of its genome,
      with ORFs suggestive of a phenotype of increased virulence and metabolic
      quiescence. Specific expression of characterized sRNAs aligned with the genomic
      response to presumably coordinate the adaptive changes necessary for this
      homeostatic mixed-species biofilm and sRNAs may provide viable foci for the
      design of future therapeutics.

PMID- 27868364
TI  - Production and characterization of polyhydroxybutyrate from Vibrio harveyi MCCB
      284 utilizing glycerol as carbon source.
AB  - AIMS: Production and characterization of polyhydroxybutyrate (PHB) from
      moderately halophilic bacterium Vibrio harveyi MCCB 284 isolated from tunicate
      Phallusia nigra. METHODS AND RESULTS: Twenty-five bacterial isolates were
      obtained from tunicate samples and three among them exhibited an orange
      fluorescence in Nile red staining indicating the presence of PHB. One of the
      isolates, MCCB 284, which showed rapid growth and good polymer yield, was
      identified as V. harveyi. The optimum conditions of the isolate for the PHB
      production were pH 8.0, sodium chloride concentration 20 g l-1 , inoculum size
      0.5% (v/v), glycerol 20 g l-1 and 72 h of incubation at 30 degrees C. Cell dry
      weight (CDW) of 3.2 g l-1 , PHB content of 2.3 g l-1 and final PHB yield of 1.2 g
      l-1 were achieved. The extracted PHB was characterized by FTIR, NMR and DSC-TGA
      techniques. CONCLUSIONS: An isolate of V. harveyi that could effectively utilize
      glycerol for growth and PHB accumulation was obtained from tunicate P. nigra. PHB
      produced was up to 72% based on CDW. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      is the first report of an isolate of V. harveyi which utilizes glycerol as the
      sole carbon source for PHB production with high biomass yield. This isolate could
      be of use as candidate species for commercial PHB production using glycerol as
      the feed stock or as source of genes for recombinant PHB production or for
      synthetic biology.

PMID- 27868365
TI  - The salience of the self: Self-referential processing and internalizing problems
      in children and adolescents with autism spectrum disorder.
AB  - Children and adolescents with autism spectrum disorder (ASD) demonstrate atypical
      processing of, and memory for, self-referenced information, which may contribute
      to the heightened rates of co-occurring internalizing problems. We assessed
      affective and cognitive aspects of self-referential processing in verbally-fluent
      children with ASD (N = 79), and an age-matched comparison sample (COM, N = 73) of
      children without an autism diagnosis. We examined group differences in these two
      aspects of the self-system, and their joint contributions to individual
      differnces in internalizing problems. Using a self-referenced memory (SRM) task,
      participants indicated whether a series of positive and negative trait adjectives
      described themselves and a well-known fictional character. Participants were then
      surprised with a recognition memory test on the same adjectives. Overall,
      individuals with ASD showed a reduction in the extent to which they
      preferentially endorsed positive over negative trait adjectives about themselves,
      and a reduction in their preferential memory for self- over other-referenced
      information. Across the full sample, these two aspects of self-referential
      processing jointly predicted self-reported internalizing problems. Specifically,
      self-evaluations were strongly and inversely associated with internalizing
      problems but only for children with relatively high SRM. These findings suggest
      that the salience of the self influences the extent to which affective self
      evaluations impact emotional functioning for youth both with and without ASD.
      Implications for basic (e.g., developmental) and translational (e.g.,
      intervention) research are discussed. Autism Res 2017, 10: 949-960. (c) 2016
      International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27868367
TI  - Applying Aspects of the Expert Performance Approach to Better Understand the
      Structure of Skill and Mechanisms of Skill Acquisition in Video Games.
AB  - Video games are ideal platforms for the study of skill acquisition for a variety
      of reasons. However, our understanding of the development of skill and the
      cognitive representations that support skilled performance can be limited by a
      focus on game scores. We present an alternative approach to the study of skill
      acquisition in video games based on the tools of the Expert Performance Approach.
      Our investigation was motivated by a detailed analysis of the behaviors
      responsible for the superior performance of one of the highest scoring players of
      the video game Space Fortress (Towne, Boot, & Ericsson, ). This analysis revealed
      how certain behaviors contributed to his exceptional performance. In this study,
      we recruited a participant for a similar training regimen, but we collected
      concurrent and retrospective verbal protocol data throughout training. Protocol
      analysis revealed insights into strategies, errors, mental representations, and
      shifting game priorities. We argue that these insights into the developing
      representations that guided skilled performance could only easily have been
      derived from the tools of the Expert Performance Approach. We propose that the
      described approach could be applied to understand performance and skill
      acquisition in many different video games (and other short- to medium-term skill
      acquisition paradigms) and help reveal mechanisms of transfer from gameplay to
      other measures of laboratory and real-world performance.

PMID- 27868366
TI  - Effects of gemigliptin, a dipeptidyl peptidase-4 inhibitor, on lipid metabolism
      and endotoxemia after a high-fat meal in patients with type 2 diabetes.
AB  - We aimed to investigate the effects of gemigliptin, a dipeptidyl peptidase-4
      inhibitor, on postprandial lipoprotein levels and endotoxemia in a randomized,
      double-blind, placebo-controlled, crossover study. Ten people with type 2
      diabetes mellitus (T2DM), inadequately controlled with oral antidiabetic
      medications and/or lifestyle modification, were randomized to gemigliptin or
      placebo for 4 weeks. At the end of each treatment phase, the study participants
      underwent a high-fat meal tolerance test and needle aspiration of abdominal
      subcutaneous adipose tissue. The median (range) fasting and total area under the
      curve of apolipoprotein B48 (ApoB48) were significantly lower with gemigliptin
      than with placebo (2.9 [1.5-15.8] ug/mL vs 4.2 [1.3-23.4] ug/mL; P = .020; 35.3
      [14.4-87.4] ug/mL * hour vs 42.2 [17.5-109.0] ug/mL * hour; P = .020,
      respectively), whereas apolipoprotein B100 showed no significant difference.
      Serum endotoxin levels were undetectable in 70% of the samples, so we were not
      able to evaluate the effect of gemigliptin on endotoxemia. The gene expression of
      inflammatory cytokines in subcutaneous adipose tissue was not affected by
      gemigliptin. Gemigliptin reduced ApoB48 levels after a high-fat meal in
      participants with T2DM. Whether systemic endotoxin levels can be reduced by
      gemigliptin requires further investigation.

PMID- 27868368
TI  - A quantitative analysis of the quality and content of the health advice in
      popular Australian magazines.
AB  - OBJECTIVE: To examine how health advice is provided in popular magazines and the
      quality of that advice. METHODS: A prospective quantitative analysis of the
      quality of health advice provided in Australian magazines between July and
      December 2011 was conducted. A rating instrument was adapted from the Media
      Doctor Australia rating tool used to assess quality of health news reporting.
      Criteria included: recommends seeing a doctor; advice based on reliable evidence;
      advice clear and easily applied; benefits presented meaningfully; potential harms
      mentioned; evidence of disease mongering; availability and cost of treatments;
      obvious advertising; vested interest, and anecdotal evidence. RESULTS: 163 health
      advice articles were rated showing a wide variation in the quality of advice
      presented between magazines. Magazines with 'health' in the title, rated most
      poorly with only 36% (26/73) of these articles presenting clear and meaningful
      advice and 52% (38/73) giving advice based on reliable evidence. CONCLUSIONS:
      Australian magazines, especially those with health in the title, generally
      presented poor quality, unreliable health advice. Teen magazine Dolly provided
      the highest quality advice. IMPLICATIONS: Consumers need to be aware of this when
      making health choices.

PMID- 27868369
TI  - Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a
      multinational study.
AB  - INTRODUCTION: There has been increasing recognition in recent years that female
      carriers of haemophilia manifest abnormal bleeding; however, data on the use of
      bleeding assessment tools in this population are lacking. AIM: Our objective was
      to validate the ISTH-BAT in haemophilia carriers to describe bleeding symptoms
      and allow for comparisons with factor levels and other patient groups. METHODS:
      This was a prospective, observational, cross-sectional study performed by members
      of Global Emerging HEmostasis Panel (GEHEP). Unselected consecutive haemophilia
      carriers were recruited and a CRF and the ISTH-BAT were completed by study
      personnel. RESULTS: A total of 168 haemophilia carriers were enrolled: 155
      haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20-82).
      Carriers had higher mean bleeding scores (BS) compared with age-matched controls
      (n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC (n = 32; 3.0; P = 0.009),
      but lower BS compared with women with Type 1 VWD (n = 83; 8.7; P < 0.0001).
      Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX
      levels. There was a significant but weak negative correlation between BS and
      factor level (Spearman's r2  = -0.36, P < 0.001). CONCLUSION: Our results show
      that haemophilia carriers experience abnormal bleeding, including haemarthrosis.
      Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC >
      controls. Understanding the performance of the ISTH-BAT in this population is a
      critical step in future research aimed at investigating the underlying
      pathophysiology of abnormal bleeding, with the ultimate goal of optimizing
      treatment.

PMID- 27868370
TI  - Chemical vs. radioactive synoviorthesis for treatment of chronic haemophilic
      synovitis: Syrian experience.

PMID- 27868371
TI  - A bodyweight-dependent allometric exponent model for scaling clearance of
      clotting factor VIII and IX from infants to adults.

PMID- 27868372
TI  - Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere
      with glycaemic recovery or gastric emptying rate during hypoglycaemia: A
      randomized, placebo-controlled, double-blind, parallel-group study.
AB  - AIM: Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential
      treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs
      inhibit glucagon secretion and delay the gastric emptying (GE) rate and may
      impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA
      liraglutide on counterregulatory responses and GE rate during hypoglycaemia in
      persons with T1D. MATERIALS AND METHODS: In a 12-week, randomized, double-blind,
      placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c >=8% (64
      mmol/mol) were randomly assigned (1:1) to liraglutide 1.2 mg once daily or
      placebo as add-on to insulin treatment. Before and at end of treatment a
      hypoglycaemic clamp (plasma glucose target 2.5 mmol/L) was carried out, followed
      by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under
      the paracetamol curve and time to peak). Secondary endpoints included changes in
      glycaemic recovery, counter-regulatory hormones, pancreatic polypeptide (PP), GLP
      1, blood pressure and heart rate. RESULTS: During the period June 2013 to October
      2014, 20 patients were enrolled. After 12 weeks of treatment, changes in GE rates
      did not differ significantly between groups ( P  = .96), with no significant
      changes from baseline, whether evaluated from AUCs or time to peak. The secondary
      endpoints, glycaemic recovery, counter-regulatory hormone responses, systolic
      blood pressure and GLP-1 and PP responses, were also similar. Heart rate
      increased with liraglutide from 69 +/- 4 to 80 +/- 5 beats/min ( P  = .02).
      CONCLUSIONS: Liraglutide does not compromise glycaemic recovery, GE rate or
      counter-regulatory hormone responses in T1D patients during hypoglycaemia. No
      treatment-related safety issues were identified.

PMID- 27868373
TI  - Acute myeloid leukemia in Baraitser-Winter cerebrofrontofacial syndrome.
AB  - Baraitser-Winter malformation syndrome (BWMS), Fryns-Aftimos syndrome (FA), and
      craniofrontofacial syndromes (CFFs) have all been recently proposed to be part of
      the same phenotypic spectrum of Baraitser-Winter cerebrofrontofacial syndrome
      (BWCFF), which is characterized by facial dysmorphism, ocular coloboma, brain
      malformations, and intellectual disabilities. In addition to that, the recent
      discovery of missense mutations in one of the two ubiquitously expressed
      cytoplasmic beta- and gamma-acting-encoding genes ACTB (7p22.1) and ACTG1
      (17q25.3) in patients carrying a clinical diagnosis of BWSM, FA, or CCF has
      provided further evidence that these clinical conditions do indeed belong to the
      same entity at the molecular level. Two cases of BWCFF patients presenting with
      malignancies (i.e., acute lymphocytic leukemia and cutaneous lymphoma) have been
      published thus far. Here, we report a 21-year-old female with molecularly
      confirmed FA, who developed acute myeloid leukemia (AML). The present finding may
      indicate that actinopathies could be cancer-predisposing syndromes although small
      numbers and publication bias should be taken into account. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27868374
TI  - Automated coating procedures to produce poly(ethylene glycol) brushes in fused
      silica capillaries.
AB  - Many bioanalytical methods rely on electrophoretic separation of structurally
      labile and surface active biomolecules such as proteins and peptides. Often poor
      separation efficiency is due to surface adsorption processes leading to protein
      denaturation and surface fouling in the separation channel. Flexible and reliable
      approaches for preventing unwanted protein adsorption in separation science are
      thus in high demand. We therefore present new coating approaches based on an
      automated in-capillary surface-initiated atom transfer radical polymerization
      process (covalent coating) as well as by electrostatically adsorbing a
      presynthesized polymer leading to functionalized molecular brushes. The
      electroosmotic flow was measured following each step of the covalent coating
      procedure providing a detailed characterization and quality control. Both
      approaches resulted in good fouling resistance against the four model proteins
      cytochrome c, myoglobin, ovalbumin, and human serum albumin in the pH range 3.4
      8.4. Further, even samples containing 10% v/v plasma derived from human blood did
      not show signs of adsorbing to the coated capillaries. The covalent as well as
      the electrostatically adsorbed coating were both found to be stable and provided
      almost complete suppression of the electroosmotic flow in the pH range 3.4-8.4.
      The coating procedures may easily be integrated in fully automated capillary
      electrophoresis methodologies.

PMID- 27868375
TI  - Understanding the origins of record linkage errors and how they affect research
      outcomes.

PMID- 27868376
TI  - N-terminal region of cysteine-rich protein (CRP) in carlaviruses is involved in
      the determination of symptom types.
AB  - Plant viruses in the genus Carlavirus include more than 65 members. Plants
      infected with carlaviruses exhibit various symptoms, including leaf malformation
      and plant stunting. Cysteine-rich protein (CRP) encoded by carlaviruses has been
      reported to be a pathogenicity determinant. Carlavirus CRPs contain two motifs in
      their central part: a nuclear localization signal (NLS) and a zinc finger motif
      (ZF). In addition to these two conserved motifs, carlavirus CRPs possess highly
      divergent, N-terminal, 34 amino acid residues with unknown function. In this
      study, to analyse the role of these distinct domains, we tested six carlavirus
      CRPs for their RNA silencing suppressor activity, ability to enhance the
      pathogenicity of a heterologous virus and effects on virus accumulation levels.
      Although all six tested carlavirus CRPs showed RNA silencing suppressor activity
      at similar levels, symptoms induced by the Potato virus X (PVX) heterogeneous
      system exhibited two different patterns: leaf malformation and whole-plant
      stunting. The expression of each carlavirus CRP enhanced PVX accumulation levels,
      which were not correlated with symptom patterns. PVX-expressing CRP with
      mutations in either NLS or ZF did not induce symptoms, suggesting that both
      motifs play critical roles in symptom expression. Further analysis using chimeric
      CRPs, in which the N-terminal region was replaced with the corresponding region
      of another CRP, suggested that the N-terminal region of carlavirus CRPs
      determined the exhibited symptom types. The up-regulation of a plant gene upp-L,
      which has been reported in a previous study, was also observed in this study;
      however, the expression level was not responsible for symptom types.

PMID- 27868377
TI  - Benson Earl Ginsburg (1918-2016): a pioneer in behavior genetics.

PMID- 27868379
TI  - Qualitative and quantitative analysis of multiple components for quality control
      of Deng-Zhan-Sheng-Mai capsules by ultra high performance liquid chromatography
      tandem mass spectrometry method coupled with chemometrics.
AB  - Deng-Zhan-Sheng-Mai capsules are a well-known traditional Chinese patent medicine
      that was developed in China for the treatment of ischemic stroke. Its quality
      control focuses on Erigerontis Herba but ignores the contributions of Ginseng
      Radix et Rhizoma, Schisandrae Chinensis Fructus, and Ophiopogonis Radix. To
      improve the quality standards for this medicine, this work reports the
      application of a systematic ultra high performance liquid chromatography tandem
      mass spectrometric method coupled with chemometrics. Three qualitative and
      quantitative parameters are established for the evaluation of quality: chemical
      profiling, the relationship between the contents of 18 compounds and the
      antioxidant activity, and chemometric analysis. A total of 55 compounds,
      including 20 phenolic acids, 10 flavonoids, 15 saponins, and 10 lignans, were
      identified. The method for the quantitative determination of the aforementioned
      18 compounds was validated. The limit of quantification ranged from 0.13 to 9.60
      ng/mL. The overall recoveries ranged from 95.31 to 103.54%. Hierarchical cluster
      analysis and principal component analysis were applied to the data of 18
      components in ten batches of samples. Nine compounds, including scutellarin, 3,5
      O-dicaffeoylquinic acid, 4,5-O-dicaffeoylquinic acid, ginsenoside Rb1,
      ginsenoside Re, ginsenoside Rg1, ophiopogonin D, schisandrin, and schisandrol B,
      are suggested as chemical markers for evaluating the quality.

PMID- 27868380
TI  - Microbiomes, metabolic errors and detection of performance enhancing drug abuse.

PMID- 27868381
TI  - Corrigendum.

PMID- 27868384
TI  - Post-Acute Rehabilitation After Total Knee Replacement: A Multicenter Randomized
      Clinical Trial Comparing Long-Term Outcomes.
AB  - OBJECTIVE: To evaluate the long-term benefit of providing a post-acute,
      outpatient group exercise program for patients following primary total knee
      replacement (TKR) surgery for osteoarthritis. METHODS: A multicenter randomized
      clinical trial was conducted in 12 Australian public and private hospital
      centers. A total of 422 participants, ages 45-75 years, were randomly allocated
      prior to hospital discharge to the post-acute group exercise program or to usual
      care and were assessed at 6 weeks, 6 months, and 12 months after surgery. The
      main outcomes were operated knee pain and activity limitations at 12 months using
      the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire.
      Secondary outcomes included health-related quality of life (Short Form 12 health
      survey), knee extension and flexion strength, stair-climb power, 50-foot walk
      speed, and active knee range of motion. RESULTS: While both allocation groups
      achieved significant improvements in knee pain and activity limitations over the
      12-month followup period, there were no significant differences in these main
      outcomes, or in the secondary physical performance measures, between the 2
      treatment allocations. Twelve months after TKR, 69% and 72% of participants
      allocated to post-acute exercise and usual acute care, respectively, were
      considered to be treatment-responders. While population normative values for self
      report measures of pain, activity limitation, and health-related quality of life
      were attained 12 months after TKR, marked deficits in physical performance
      measures remained. CONCLUSION: Providing access to a post-acute group exercise
      program did not result in greater reductions in long-term knee pain or activity
      limitations than usual care. Patients undergoing primary TKR retain marked
      physical performance deficits 12 months after surgery.

PMID- 27868385
TI  - Impact of eplerenone on cardiovascular outcomes in heart failure patients with
      hypokalaemia.
AB  - AIMS: Although hypokalaemia is common among patients with heart failure (HF), the
      prognostic significance of baseline hypokalaemia and hypokalaemia during follow
      up in HF patients receiving a mineralocorticoid receptor antagonist (MRA) remains
      uncertain. METHODS AND RESULTS: Results of the EMPHASIS-HF trial in patients (n =
      2737) with HF and reduced EF with mild symptoms, randomized to eplerenone or
      placebo, were analysed with regard to the presence or occurrence of hypokalaemia
      (serum K+ <4.0 mmol/L) and the risk of cardiovascular death or hospitalization
      for HF (primary endpoint). Median follow-up was 21 months. Baseline hypokalaemia
      and hypokalaemia during follow-up were common occurrences (19.6% and 40.6%,
      respectively). Hypokalaemia during follow-up was associated with worse outcomes
      in multivariable analyses [hazard ratio (HR) 1.26, 95% confidence interval (CI)
      1.05-1.52, P = 0.01] without evidence of interaction with eplerenone. In
      contrast, baseline hypokalaemia was associated with outcomes in the placebo group
      (HR 1.37, 95% CI 1.05-1.79, P = 0.02) but not in the eplerenone group (HR 0.87,
      95% CI 0.62-1.23, P = 0.44; P for interaction = 0.04). Concurrently, eplerenone
      was found to be more protective in patients with baseline hypokalaemia vs.
      patients without baseline hypokalaemia compared with placebo (HR 0.44, 95% 0.30
      0.64, P < 0.0001 vs. 0.69, 95% CI 0.57-0.83, P = 0.0001; P for interaction =
      0.04). In patients without baseline hypokalaemia, eplerenone use decreased the
      rate of hypokalaemia during follow-up (HR 0.69, 95% CI 0.59-0.80, P < 0.001). A
      potassium level >4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6
      51.4%) of the eplerenone treatment effect (P = 0.04). CONCLUSION: In HF patients
      receiving optimal therapy but not treated with eplerenone, baseline hypokalaemia
      was associated with worse outcomes. Conversely, hypokalaemia amplified the
      treatment effect of eplerenone.

PMID- 27868387
TI  - Polymetallic nodules, sediments, and deep waters in the equatorial North Pacific
      exhibit highly diverse and distinct bacterial, archaeal, and microeukaryotic
      communities.
AB  - Concentrated seabed deposits of polymetallic nodules, which are rich in
      economically valuable metals (e.g., copper, nickel, cobalt, manganese), occur
      over vast areas of the abyssal Pacific Ocean floor. Little is currently known
      about the diversity of microorganisms inhabiting abyssal habitats. In this study,
      sediment, nodule, and water column samples were collected from the Clarion
      Clipperton Zone of the Eastern North Pacific. The diversities of prokaryote and
      microeukaryote communities associated with these habitats were examined.
      Microbial community composition and diversity varied with habitat type, water
      column depth, and sediment horizon. Thaumarchaeota were relatively enriched in
      the sediments and nodules compared to the water column, whereas
      Gammaproteobacteria were the most abundant sequences associated with nodules.
      Among the Eukaryota, rRNA genes belonging to the Cryptomonadales were relatively
      most abundant among organisms associated with nodules, whereas rRNA gene
      sequences deriving from members of the Alveolata were relatively enriched in
      sediments and the water column. Nine operational taxonomic unit (OTU)s were
      identified that occur in all nodules in this dataset, as well as all nodules
      found in a study 3000-9000 km from our site. Microbial communities in the
      sediments had the highest diversity, followed by nodules, and then by the water
      column with <1/3 the number of OTUs as in the sediments.

PMID- 27868386
TI  - Structure of the transmembrane domain of HIV-1 envelope glycoprotein.
AB  - HIV-1 envelope spike (Env) is a heavily glycosylated, type I membrane protein
      that mediates fusion of viral and cell membranes to initiate infection. It is
      also a primary target of neutralizing antibodies and thus an important candidate
      for vaccine development. We have recently reported a nuclear magnetic resonance
      structure of the transmembrane (TM) domain of HIV-1 Env reconstituted in a
      membrane-like environment. Taking HIV-1 as an example, we discuss here how a TM
      domain can anchor, stabilize, and modulate a viral envelope spike and how its
      high-resolution structure can contribute to understanding viral membrane fusion
      and to immunogen design.

PMID- 27868388
TI  - In Vitro lipolysis is associated with whole-body lipid oxidation and weight gain
      in humans.
AB  - OBJECTIVE: To assess the association of adipocyte size with cellular lipolysis
      and between cellular lipolysis and whole-body lipid oxidation. This study also
      assessed the association between adipocyte size and cellular lipolysis with
      weight and fat mass gain. METHODS: Subjects had assessment of percent body fat
      (%fat) and adipose tissue biopsy for in vitro lipolysis (n = 325), and a subset
      of subjects had measurement of whole-body lipid oxidation (n = 112). A subset of
      subjects (n = 243) returned for repeated measurements of body weight and
      composition (mean follow-up 8.2 +/- 5.5 years). RESULTS: In vitro lipolysis (r =
      0.47, P < 0.0001) and adipocyte size (r = 0.49, P < 0.0001) were strongly
      associated with %fat. In vitro lipolysis (P = 0.04) but not adipocyte size (P =
      0.44) was associated with whole-body fat oxidation. Adipocyte size was not
      associated with rate of percent weight gain (P = 0.20) but was negatively
      associated with rate of percent fat mass gain (P = 0.01). In vitro lipolysis was
      negatively associated with rate of percent weight gain (P = 0.02) and had a
      marginal negative association with rate of percent fat mass gain (P = 0.08).
      CONCLUSIONS: These results indicate inherent characteristics of adipocytes,
      including size and lipolytic activity, may be important determinants of whole
      body lipid oxidation and subsequent weight gain.

PMID- 27868389
TI  - Monitoring of Human Uterus Transplantation With Cervical Biopsies: A Provisional
      Scoring System for Rejection.
AB  - Until now, absolute uterine factor infertility has been the major untreatable
      form of female infertility. Uterus transplantation has recently proven to be the
      first successful treatment for absolute uterine factor infertility, with
      demonstration of live births. In this study, live donation uterus transplantation
      was performed in nine women. In total, 163 cervical biopsies (149 protocol, 14
      follow-up) were taken to detect histopathological signs of rejection. Based on
      experience from animal experiments, we used a three-grade scoring system to
      evaluate biopsies systematically. Nine episodes of rejection were diagnosed in
      five patients: grade 1 in six episodes, grade 2 in two episodes, and grade 3 in
      one episode. Treatment decisions were based on histopathology, and all rejection
      episodes were reversed after treatment. The biopsies were reviewed
      retrospectively, and immunohistochemistry was performed to characterize the
      inflammatory infiltrates. A borderline category was introduced to avoid
      overtreatment of patients. Based on our review of all biopsies, we put forward a
      simple grading system for monitoring of rejection and to guide immunosuppressive
      treatment in uterus transplantation.

PMID- 27868392
TI  - Cerebellar gray matter differentiates children with early language delay in
      autism.
AB  - Early language delay (ELD) is one of the earliest indicators of autism spectrum
      disorder (ASD), and predicts later cognitive and behavioral outcomes. We aimed to
      determine the neural correlates of ELD in autism, and examine the relationships
      between gray matter (GM), age of first word/phrase, and core ASD symptoms. We
      used voxel-based morphometry to examine whole-brain differences in GM in 8-13
      year old children with autism (n = 13 ELD; n = 22 non-ELD) and 35 age-matched
      typically developing (TD) children. Multiple regression analyses examined the
      relationships between GM, age of first word/phrase, and autism diagnostic
      observation schedule (ADOS) scores. Composite age of first word/phrase negatively
      correlated with GM throughout the cerebellum. Both ASD groups (ELD and non-ELD)
      had reduced GM in right cerebellar Crus I/II when compared to TD children. Left
      cerebellar Crus I/II was the only region in the brain that differentiated ELD and
      non-ELD children, with ELD children showing reduced GM relative to both non-ELD
      and TD groups. Group*score interactions converged in left Crus I/II, such that
      the non-ELD group showed poorer ADOS scores with increasing GM, whereas the ELD
      group showed poorer ADOS scores as GM decreased. Reduced GM in right cerebellar
      Crus I/I was related ASD diagnosis, while children with ELD showed additional
      reduced GM in left Crus I/II. These findings highlight the importance of specific
      cerebellar networks in both ASD and early language development, and suggest that
      bilateral disruption in cerebellar regions that interconnect with fronto-parietal
      networks could impact language acquisition in ASD. Autism Res 2016, 9: 1191-1204.
      (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27868393
TI  - Atypical effective connectivity of thalamo-cortical circuits in autism spectrum
      disorder.
AB  - Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by
      atypical connectivity within and across multiple brain systems. We aimed to
      explore information transmission from the sensory periphery to information
      processing centers of the brain across thalamo-cortical circuits in ASD. A large
      multicenter dataset from the autism brain imaging data exchange was utilized. A
      thalamus template derived from the Automatic Anatomic Labeling atlas was
      subdivided into six subregions corresponding to six cortical regions using a
      "winner-takes-all" strategy. Granger causality analysis (GCA) was then applied to
      calculate effective connectivity from subregions of the thalamus to the
      corresponding cortical regions. Results demonstrate reduced effective
      connectivity from the thalamus to left prefrontal cortex (P = 0.023), right
      posterior parietal cortex (P = 0.03), and bilateral temporal cortex (left: P =
      0.014; right: P = 0.015) in ASD compared with healthy control (HC) participants.
      The GCA values of the thalamus-bilateral temporal cortex connections were
      significantly negatively correlated with communication scores as assessed by the
      autism diagnostic observation schedule in the ASD group (left: P = 0.037; right:
      P = 0.007). Age-related analyses showed that the strengths of the thalamus
      bilateral temporal cortex connections were significantly positively correlated
      with age in the HC group (left: P = 0.013; right: P = 0.016), but not in the ASD
      group (left: P = 0.506; right: P = 0.219). These results demonstrate impaired
      thalamo-cortical information transmission in ASD and suggest that atypical
      development of thalamus-temporal cortex connections may relate to communication
      deficits in the disorder. Autism Res 2016, 9: 1183-1190. (c) 2016 International
      Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27868394
TI  - Sensitivity and accuracy of hybrid fluorescence-mediated tomography in deep
      tissue regions.
AB  - Fluorescence-mediated tomography (FMT) enables noninvasive assessment of the
      three-dimensional distribution of near-infrared fluorescence in mice. The
      combination with micro-computed tomography (uCT) provides anatomical data,
      enabling improved fluorescence reconstruction and image analysis. The aim of our
      study was to assess sensitivity and accuracy of uCT-FMT under realistic in vivo
      conditions in deeply-seated regions. Accordingly, we acquired fluorescence
      reflectance images (FRI) and uCT-FMT scans of mice which were prepared with
      rectal insertions with different amounts of fluorescent dye. Default and high
      sensitivity scans were acquired and background signal was analyzed for three FMT
      channels (670 nm, 745 nm, and 790 nm). Analysis was performed for the original
      and an improved FMT reconstruction using the uCT data. While FRI and the original
      FMT reconstruction could detect 100 pmol, the improved FMT reconstruction could
      detect 10 pmol and significantly improved signal localization. By using a finer
      sampling grid and increasing the exposure time, the sensitivity could be further
      improved to detect 0.5 pmol. Background signal was highest in the 670 nm channel
      and most prominent in the gastro-intestinal tract and in organs with high
      relative amounts of blood. In conclusion, we show that uCT-FMT allows sensitive
      and accurate assessment of fluorescence in deep tissue regions.

PMID- 27868395
TI  - Genetic diagnosis in Hemophilia A from southern China: five novel mutations and
      one preimplantation genetic analysis.
AB  - INTRODUCTION: As there is currently no complete cure for hemophilia A (HA), the
      identification of pathogenic mutations in factor VIII (FVIII) gene from HA
      patients and carriers, which can contribute to genetic counseling prenatal
      diagnosis, and preimplantation genetic diagnosis (PGD), is an important step to
      prevent HA. METHODS: A total of 14 unrelated Chinese HA subjects (FVIII activity
      <40%), 20 carrier subjects, three fetuses, and one PGD were included in this
      study. We first screened for the presence of FVIII intron 22 and intron 1
      inversions. Second, the coding region of the FVIII gene was sequenced. For the
      novel mutations, FVIII mRNA expression was detected by real-time PCR and the
      protein structures were analyzed by bioinformatic tools. RESULTS: Five novel
      mutations (c.1A>C, c.304_305insA, c.1594T>A, c.6045G>A, and c.2645_2646insG) were
      found. The real-time PCR showed that the expression of FVIII mRNAs was lower in
      HA patients than in normal subjects. Prenatal diagnosis and PGD were successfully
      performed: Two of three fetuses and four of eight blastomeres were confirmed to
      be normal. CONCLUSION: In conclusion, genetic diagnosis of 14 unrelated HA
      subjects, 20 carrier subjects, three fetuses, and one PGD was successfully
      performed in our study.

PMID- 27868397
TI  - Prolonged Effect of OnabotulinumtoxinA on Chronic Migraine in 87 Koreans.

PMID- 27868396
TI  - Investigating the Prevalence of Dementia and Its Associated Risk Factors in a
      Chinese Nursing Home.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to determine the
      prevalence of and risk factors for dementia in residents aged 65 years and older
      in a Chinese nursing home. METHODS: A cross-sectional study was carried out in a
      nursing home located in Hangzhou, Zhejiang Province, China. Cognitive status,
      including the presence of dementia and mild cognitive impairment (MCI), was
      measured using a combination of medical history and objective cognitive
      assessments. Logistic regression analysis was conducted to predict the associated
      risk factors. RESULTS: In total, 943 residents (334 males and 609 females) aged
      84.00+/-6.67 years (mean+/-SD) were included. Dementia was diagnosed in 420
      (44.5%) residents, and MCI was diagnosed in 195 (20.7%). Mild, moderate, and
      severe dementia were present in 20.3%, 14.0%, and 65.7% of those in the dementia
      group, respectively. Logistic regression analysis revealed that dementia was
      associated with a low education level (p=0.000), an advanced age (p=0.010), and a
      history of stroke (p=0.023). CONCLUSIONS: Our study found a high prevalence of
      dementia in a Chinese nursing home, and a high prevalence of patients with severe
      dementia. Risk factors for dementia included a low educational level, an advanced
      age, and a history of stroke. Appropriate interventions need to be applied to
      this population.

PMID- 27868398
TI  - Real-Time Detection of Cerebral Artery Rebleeding by Transcranial Doppler
      Ultrasound: Hemodynamic Changes and Response to Treatment.

PMID- 27868399
TI  - Electron Microscopy Pathology of ADSSL1 Myopathy.

PMID- 27868401
TI  - Back Pain and Spinal Cysticercosis.

PMID- 27868400
TI  - Association between Stroke Status and Depression in a Community Setting: The 2014
      Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND AND PURPOSE: Previous studies have examined the risk factors for
      depression in stroke patients, but little information is available on the
      relationship between stroke status and depression in the community-dwelling
      general population. We evaluated the association between stroke status and
      depression using representative nationwide data. METHODS: In total, 3,487
      subjects (aged >=40 years) who participated in version VI-2 of the sixth Korea
      National Health and Nutrition Examination Survey (KNHANES) performed in 2014 were
      included. We compared the prevalence of depression in 120 community-dwelling
      stroke patients and 3,367 nonstroke controls using the nine-item Patient Health
      Questionnaire (PHQ-9). RESULTS: The prevalence of depression (PHQ-9 score >=10)
      was 16.7% in stroke patients and 6.4% in controls. In the unadjusted model,
      depression was more common in stroke patients than in nonstroke controls [odds
      ratio (OR), 2.95; 95% confidence interval (CI), 1.79-4.86]. After adjusting for
      demographic characteristics, socioeconomic status, health-related behaviors, and
      comorbidities, stroke diagnosis was a significant risk factor for depression (OR,
      1.85; 95% CI, 1.06-3.24). Specifically, a diagnosis of stroke in patients aged
      <60 years (OR, 3.82; 95% CI, 1.81-8.09) and the presence of stroke complications
      (OR, 2.77; 95% CI, 1.25-6.13) remained significant risk factors for depression
      even after adjusting for potential confounders. CONCLUSIONS: In a community
      setting, poststroke survivors had a higher prevalence of depression, and stroke
      was an independent risk factor for depression. Public psychosocial interventions
      are needed to improve the mental health care of community-dwelling stroke
      survivors.

PMID- 27868402
TI  - Mechanical Thrombectomy for Acute Middle Cerebral Artery Occlusion Caused by a
      Giant, Thrombosed, Extracranial Internal Carotid Artery Aneurysm.

PMID- 27868403
TI  - Clinical and Pathological Findings of a Korean Family with Pathogenic Variants of
      the TTN Gene.

PMID- 27868404
TI  - [Standardization of cancer biobank in precision medicine era].
AB  - Tumor specimens have a great role in basic and clinical translational researches
      on cancer, especially in the era of precision medicine. Thus the standardization
      of cancer biobank is of high importance. The establishment and maintenance of
      cancer biobank require comprehensive quality management, so as to provide high
      quality service for basic and clinical researches. At present, sample-oriented
      collection and management, and clinical and pathological data annotation are the
      main focuses of biobank standardization in China.

PMID- 27868405
TI  - [Expression of CD10 in tumor-associated fibroblast of cancerized or recurrent
      colorectal adenomas].
AB  - Objective: To investigate the expression of CD10 in tumor-associated fibroblasts
      (TAF) in colorectal adenomas and its relation to cancerization and recurrence of
      adenoma. Methods: Tissue samples of low-grade adenoma (n=50), high-grade adenoma
      (n=50) and colorectal adenocarcinoma (n=50) were collected, and tissue samples at
      the distal margin of corresponding colorectal lesions were taken as controls. The
      expression of CD10 in the stromal TAFs, and the expressions of beta-catenin, Ki
      67, p53 and CyclinD1 in tumor cells were detected by immunohistochemistry
      (Envision). The correlation of CD10 expression in stromal TAFs with the
      expressions of beta-catenin, Ki-67, p53 and CyclinD1 in tumor cells was analyzed
      by Spearmen. One hundred samples of low-grade colorectal adenoma were collected,
      including 57 non-recurrent cases and 43 recurrent cases (16 cases of recurrent
      adenoma and 27 cases of recurrent adenocarcinoma); the expression of stromal TAF
      CD10 were determined and compared among groups. Results: There was no TAF in
      normal colorectal mucosa. The expression rates of TAF CD10 in low-grade adenoma,
      high-grade adenoma and colorectal adenocarcinoma were 22%, 50% and 78%,
      respectively (all P<0.05). The expression of Ki-67 and beta-catenin in low-grade
      adenoma, high-grade adenoma, colorectal adenocarcinoma was on a rising trend (all
      P<0.01). The expression of CyclinD1 in high-grade adenoma was higher than that in
      colorectal adenocarcinoma and low-grade adenoma (all P>0.05). The expression of
      p53 in colorectal adenocarcinoma and high-grade adenoma was higher than that in
      low grade adenoma (all P<0.01). The expression of TAF CD10 was correlated with
      the expression of p53, Ki-67 and beta-catenin-nucleus(r=0.264,0.307,0.320, all
      P<0.01),but not correlated with CyclinD1 and beta-catenin-membrane (r=0.012,
      0.073, all P>0.05). The TAF CD10 level was significantly higher in low-grade
      adenoma with recurrence than that in those without recurrence (P<0.05).The
      expression of CD10 in recurrent colorectal adenocarcinoma was higher than that in
      recurrent adenoma (P<0.05). Conclusion: The expression of TAF CD10 is increased
      gradually in the process of adenoma-cancer, indicating that it may play an
      important role in the canceration of adenoma. Adenomas with high expression of
      CD10 TAF are likely to be recurrent and cancerized, and detection of TAF CD10
      combined with p53, Ki-67 and beta-catenin may be of value in predicting
      canceration or recurrence of colorectal adenoma.

PMID- 27868406
TI  - [Expression of miR-let-7e-3p in cervical intraepithelial neoplasm and cervix
      carcinoma and its clinical significance].
AB  - Objective: To investigate the expression of microRNA (miRNA, miR) let-7e-3p in
      different cervical lesions and its clinical significance. Methods: The expression
      of miR-let-7e-3p in the tissues of normal cervix (n=26), high-grade squamous
      intraepithelial lesion (HSIL) (n=37), and cervix carcinoma (n=101) were detected
      by reverse transcription and quantitative polymerase chain reaction (RT-qPCR).
      The correlation of miR-let-7e-3p expression with the clinicopathological
      parameters of patients with cervical cancer was analyzed. miR-let-7e-3p mimic was
      transfected into cervical carcinoma Siha cells. The cell cycle and apoptosis were
      determined by flow cytometry; cell proliferation was determined by CCK-8 kit; and
      the migration and invasion of cells were determined by Transwell assay. Results:
      The relative expression levels of miR-let-7e-3p in normal cervix, HSIL, and
      cervical carcinoma were 1.45+/-0.24, 0.79+/-0.05 and 0.46+/-0.04, respectively
      (all P<0.05). After transfection with miR-let-7e-3p mimic, the S-phase fraction
      and apoptosis rate of Siha cells were increased significantly compared with
      control group[(29.76+/-6.6)% vs (13.38+/-1.3)%, P<0.05; (5.98+/-1.38)% vs (3.53+/
      0.79)%, P<0.05, respectively]. OD of transfected Siha cells at 48, 72 and 96 h
      were 0.57+/-0.11,0.65+/-0.04 and 0.84+/-0.14, which were significantly lower than
      those of untransfected Siha cells (0.74+/-0.05, 0.93+/-0.10 and 1.47+/-0.14, all
      P<0.05). The migration and invasion abilities of transfected Siha cells were not
      significantly changed (all P>0.05). Conclusion: The expression of miR-let-7e-3p
      is down-regulated in cervical neoplasms, which is associated with cell cycle
      arrest and proliferation inhibition of cervical cancer cells.

PMID- 27868408
TI  - [Effect of a novel EZH2 inhibitor GSK126 on prostate cancer cells].
AB  - Objective: To investigate the effect of a novel EZH2 inhibitor GSK126 on cell
      growth, apoptosis and migration of prostate cancer cells. Methods: Prostate
      cancer PC-3 and DU145 cells were treated with GSK126 at different doses. Cell
      growth was detected by sulforhodamine assay. Cell apoptosis was assayed by
      Annexin V-/PI kit. Transwell chamber and wound healing assays were conducted to
      detect cell migration. The mRNA level was detected by quantitative PCR, and
      protein expression was detected by Western blot analysis. Results: GSK126 showed
      significant effect on cell growth and apoptosis when the dose was higher than 50
      MUmol/L. Wound healing assay revealed that scratch space in PC-3 cells was
      significantly increased in a dose-dependent manner in GSK126-treated
      groups[(247.2+/-24.4),(347.2+/-19.2) and (410.5+/-18.1) MUm in low, medium and
      high dose (5.0, 20.0, 50.0 MUmol/L), respectively] as compared with the control
      group[(171.3+/-17.8) MUm](all P<0.05). Transwell assay showed that migrated PC-3
      cells in control group was 322.0+/-17.9,while those in GSK126-treated groups were
      198.3+/-15.4 (low),82.7+/-6.2 (medium) and 30.2+/-4.1 (high), and the differences
      between the control group and GSK126-treated groups were significant(all P<0.05).
      In addition, GSK126 up-regulated E-cadherin mRNA expression and down-regulated N
      cadherin and Vimentin mRNA expression, whereas had no significant effect on
      Snail, Fibronectin and VEGF-A mRNA expression. The protein expression of E
      cadherin was elevated but VEGF-A protein did not change in GSK126-treated groups.
      Similar results were exhibited in DU145 cell. Conclusion: GSK126 can
      significantly inhibit cell migration and invasion in prostate cancer PC-3 and
      DU145 cells, which may be resulted from its effect on epithelial-mesenchymal
      transition. GSK126 may be used as a potential anti-prostate cancer dug in clinic.

PMID- 27868407
TI  - [Effect of DJ-1 silencing by RNA interference on growth of xenografted human
      laryngeal squamous cell carcinoma Hep-2 cells in nude mice].
AB  - Objective: To investigate the effect of silencing DJ-1 on xenografted human
      laryngeal squamous cell carcinoma (LSCC) Hep-2 cells in nude mice. Methods:
      Xenograft model of human LSCC was established by subcutaneous transplantation of
      Hep-2 cells in 24 nude mice. The LSCC-bearing nude mice were randomly divided
      into 3 groups (n=8 in each):DJ-1 siRNA low dose group and DJ-1 siRNA high dose
      group were injected in tumors with 20 MUg of DJ-1 siRNA or 40 MUg of DJ-1 siRNA
      in 50 MUL, respectively; control group was injected with 5% glucose solution in
      50 MUL, twice a week for 3 weeks. The weight and size of tumors were measured
      before injection. The animals were sacrificed 48 h after the final treatment, and
      the tumors were harvested and weighed. The apoptosis and proliferation of tumor
      cells were determined; the expressions of Caspase-3 and Ki-67 in tumor specimens
      were detected with immunohistochemistry. The expression of DJ-1, PTEN, survivin
      mRNA and protein in tumor tissues were detected by RT-PCR and Western blotting,
      respectively. Results: Tumor weight in low dose group[(0.66+/-0.15)g] and high
      dose group[(0.48+/-0.11)g] were significantly lower than that in control
      group[(0.83+/-0.16)g, all P<0.05]. The inhibition rates of low dose group and
      high dose group were (20.48+/-0.18)% and (42.16+/-0.13)%, respectively.
      Immunohistochemistry showed that the expression of Caspase-3 was increased and Ki
      67 was reduced in tumor specimens, compared with the control group (all P<0.05).
      RT-PCR and Western blot results showed that in low dose group and high dose group
      the mRNA and protein expression of DJ-1 and survivin significantly decreased (all
      P<0.05), while PTEN mRNA and protein content increased (all P<0.05). Conclusion:
      High dose DJ-1 siRNA can inhibit the tumor growth in human LSCC xenograft nude
      mouse model, which indicates that down-regulating DJ-1 and survivin, and up
      regulating PTEN expression may lead to blockage of PI3K-PKB/Akt signaling pathway
      and promoting tumor cell apoptosis.

PMID- 27868409
TI  - [Effect of RAD18-siRNA on proliferation and chemotherapy sensitivity of human
      esophageal squamous cell carcinoma ECA-109 cells].
AB  - Objective: To investigate the effect of RAD18-siRNA on cell proliferation and
      chemotherapy sensitivity of esophageal squamous cell carcinoma (ESCC) ECA-109
      cells. Methods: RAD18-siRNA was transfected into human ECA-109 cells by
      Lipofectamine 3000. Quantitative PCR and Western blot were performed to detect
      RAD18 and CyclinD1 expression; CCK-8 assay was used to determine cell
      proliferation and chemotherapy drug sensitivity; flow cytometry was used to
      determine cell cycle. Correlation between RAD18 and CyclinD1 mRNA expression was
      analyzed by Pearson's correlation. Results: Compared with non-transfected cells,
      the expression of RAD18 in RAD18-siRNA group was significantly decreased
      (P<0.05). The cell proliferation was inhibited (P<0.05) and the cell number of G1
      phase was increased, G2/M phase cells decreased (P<0.05) in RAD18-siRNA group.
      After treatment with different concentrations of cisplatin or 5-FU, the survival
      rate of the two cell groups was reduced (all P<0.05), and the IC50 of RAD18-siRNA
      group was significantly lower than that of non-transfected group (P<0.05). The
      mRNA expression of RAD18 was positively correlated with CyclinD1 expression in
      ESCC tissues(r=0.478, P<0.01). Conclusion: Down-regulated expression of RAD18 can
      decrease the cell proliferation and increase chemo-sensitivity of ESCC cells, and
      CyclinD1 may participate in the process.

PMID- 27868410
TI  - [Expression of microRNA-221/222 in patients with monoclonal gammopathy of
      undetermined significance and multiple myeloma].
AB  - Objective: To detect the expression of miR-221/222 in serum and plasma cells in
      patients with monoclonal gammopathy of undetermined significance(MGUS) and
      multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers
      in the diagnosis and prognosis predicting of MGUS and MM. Methods: Bone marrow
      and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with
      newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run
      Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province
      during January 2013 and December 2015. The expressions of miR-221/222 in serum
      and in sorted CD138 positive plasma cells were detected by qRT-PCR, and the
      relative expression of miR-221/222 (Deltact) was compared between the groups.
      Serum levels of miR-221 before and after treatment were compared in both
      remission group (n=22) and refractory group (n=13) in MM patients, and its
      correlation with serum level of beta2-MG was assessed using Pearson's correlation
      analysis. Results: Serum levels of miR-221/222 in MGUS and MM groups were
      significantly higher than those in control group (all P<0.01), while miR-221/222
      levels in plasma cells were significantly lower in MGUS and MM groups than those
      in the control group (P<0.05 or<0.01). No significant difference in miR-221/222
      levels in serum and plasma cells was observed between MGUS group and MM group
      (all P>0.05). There was no correlation between miR-221/222 levels in serum and
      plasma cells (r=0.024 and -0.127, all P>0.05), but miR-221 levels were correlated
      with miR-222 levels in both serum and plasma cells (r=0.534 and 0.552, all
      P<0.01). Receiver operating characteristic (ROC) curves showed that the areas
      under the curve (AUCs) of serum miR-221/222, plasma cell miR-221/222 in diagnosis
      of MGUS/MM were 0.968, 0.976, 0.801 and 0.727, respectively. There was no
      significant difference in serum level of miR-221 among MM patients with different
      paraprotein isotypes (P>0.05), but serum level of miR-221 in patients with
      relapsed MM was higher than that in patients with newly diagnosed MM (P<0.01).
      Compared with the patients with MGUS or MM stageI and II, patients with MM stage
      III were of higher serum levels of miR-221 (P<0.01). Serum level of miR-221
      decreased after chemotherapy in the remission group (U=51.5, P<0.01), but such
      decrease was not observed in the refractory group (U=67.5, P>0.05). Serum level
      of beta2-MG was positively correlated with serum level of miR-221 (r=0.524,
      P<0.01). Conclusion: miR-221/222 in serum and plasma cells may be biomarkers for
      early diagnosis of MGUS, and are helpful for diagnosis and efficacy evaluation of
      MM.

PMID- 27868411
TI  - [Efficacy of neoadjuvant chemotherapy combined with bevacizumab versus
      neoadjuvant chemotherapy alone for Her2-negative breast cancer: a meta-analysis
      of randomized controlled clinical trials].
AB  - Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy
      combined with bevacizumab versus neoadjuvant chemotherapy alone for Her2-negative
      breast cancer.Methods: We searched PubMed, the Cochrane Library, Web of Science,
      CNKI, Wanfang Database and the abstracts of major international conferences in
      recent 5 years to identify prospective randomized controlled clinical trials that
      met the inclusion and exclusion criteria. Study selection and analyses were
      undertaken according to the Cochrane Handbook. Meta-analysis was performed using
      RevMan 5.3 software.Results: Six trials were identified with 4440 eligible
      patients. The results of this meta-analysis showed that the rate of pathological
      complete response (pCR) was higher in Her-2 negative breast cancer patients
      receiving bevacizumab combined with neoadjuvant chemotherapy than that in
      patients with neoadjuvant chemotherapy alone (24.7% vs 20.1%, RR=1.23, 95%CI:1.10
      1.37, P<0.01). In addition, the pCR rate rose up when bevacizumab was added to
      neoadjuvant chemotherapy both in hormone receptor-positive patients (13.1% vs
      10.2%,RR=1.28, 95%CI:1.04-1.58,P<0.05) and in hormone receptor-negative patients
      (46.3% vs 37.1%, RR=1.25, 95%CI:1.12-1.39, P<0.01). Statistical differences were
      observed in the rate of relevant adverse events such as hypertention (3.2% vs
      0.6%, RR=5.292, 95%CI:2.933-9.549, P<0.01) and mucositis (10.5% vs 2.0%,
      RR=5.340, 95%CI:3.743-7.617, P<0.01) between the combination group and the
      chemotherapy alone group. Differences in other toxicities such as febrile
      neutropenia, infection, surgical complications, neutropenia and hand-foot
      syndrome were also found to be statistically significant between the combination
      group and the chemotherapy alone group (all P<0.05), while such difference was
      not found in the occurrence of peripheral neuropathy (P>0.05). Conclusion: The
      addition of bevacizumab to neoadjuvant chemotherapy in Her2-negative breast
      cancer can significantly improve pathological complete response, but may bring
      more grade 3 and 4 toxicities.More neoadjuvant trials need to be done to define
      subgroups of Her2-negative breast cancer that would have clinically significant
      long-term benefit from bevacizumab treatment.

PMID- 27868412
TI  - [Aberrant DNA methylation and its targeted therapy in acute myeloid leukemia].
AB  - The occurrence and development of acute myeloid leukemia (AML) is not only
      related to gene mutations, but also influenced by abnormal epigenetic regulation,
      in which DNA methylation is one of the most important mechanisms. Abnormal DNA
      methylation may lead to the activation of oncogene and the inactivation of tumor
      suppressor gene, resulting in the occurrence of leukemia. The mutations of DNA
      methylation enzymes associated with AML may have certain characteristics. The AML
      with recurrent cytogenetic abnormalities is also related to abnormal methylation.
      Some fusion genes can alter DNA methylation status to participate in the
      pathogenesis of leukemia. In addition, chemotherapy drug resistance in patients
      with AML is associated with the change of gene methylation status. Considering
      the reversibility of the epigenetic modification, targeted methylation therapy
      has become a hotspot of AML research.

PMID- 27868413
TI  - [Progress on clinical application of bevacizumab for the treatment of refractory
      cervical cancer].
AB  - Bevacizumab is increasingly used in recurrent, persistent or metastatic cervical
      cancer. The early retrospective case reports found that bevacizumab combined with
      5-FU (including capecitabine) or paclitaxel was well tolerated and displayed
      encouraging anti-tumor activity in recurrent or persistent cervical cancer. Phase
      II clinical trials showed that bevacizumab was well tolerated and active in the
      second- and third-line treatment of patients with recurrent cervical cancer.
      Large scale phase II and phase III clinical trials demonstrated that bevacizumab
      containing chemotherapy was effective in the first- and second-line treatment of
      patients with persistent cervical cancer, prolonged survival time and improved
      remission rate. The article also reviews the research progress on predictive
      factors of bevacizumab efficacy, showing the use of imaging and biomarkers in
      predicting the efficacy of bevacizumab treatment. In addition, this article
      analyzes the cost-effectiveness of bevacizumab, finding that bevacizumab combined
      with chemotherapy meets the standard of cost-effectiveness.

PMID- 27868414
TI  - [Effect of shift rotation culture on formation and activity of encapsulated
      hepatocytes aggregates].
AB  - Objective: To observe the effect of uniform and shift rotation culture on the
      formation and activity of the alginate-chitosan (AC) microencapsulated HepLL
      immortalized human hepatocytes and HepG2 cells aggregates. Methods: AC
      microcapsulated HepG2 and HepLL cells were randomly divided into two groups. Each
      group was divided into 3 subgroups according to uniform and shift rotation
      culture.The size and number of aggregates were observed and measured under laser
      confocal microscopy and inverted microscope dynamically. The amount of albumin
      synthesis was detected by ELISA, the clearance of ammonia was detected by
      colorimetry, and diazepam conversion function was detected by high performance
      liquid chromatography (HPLC). Results: On day 6, 8, 10, 12, 14 and 16, the number
      and size of the aggregates, albumin synthesis, diazepam clearance and ammonium
      clearance increased significantly in shift rotation culture group than in uniform
      group (all P<0.01). The albumin synthesis, diazepam clearance, and ammonium
      clearance in the microencapsulated HepLL groups were significantly higher than
      those of HepG2 cells at any time (all P<0.01). Conclusion: Shift rotation culture
      can significantly promote the formation and increase the activity of AC
      microencapsulated HepLL and HepG2 aggregates, and HepLL cells may be more
      suitable for bioartificial liver than HepG2.

PMID- 27868415
TI  - [Association of single nucleotide polymorphism in exon of transient receptor
      potential melastatin 2 gene with sepsis].
AB  - Objective: To investigate the association between single nucleotide polymorphism
      (SNP) in the 11th exon of transient receptor potential melastatin 2 (TRPM2) gene
      with the susceptibility and outcome of sepsis. Methods: A total of 119 septic
      patients and 112 normal subjects were enrolled from the First Affiliated
      Hospital, Zhejiang University School of Medicine. Among 119 septic patients, 62
      died (fatal group) and 57 survived (survival group) within 28 days of disease
      onset. The genotypes of these individuals were detected using TaqMan allelic
      discrimination assays, and its correlations with susceptibility and outcome of
      sepsis were analyzed. Results: There was no significant difference in genotype
      frequencies and allelic frequencies of TRPM2 SNP rs1556314 between septic
      patients and the controls (all P>0.05). And no significant difference in genotype
      frequencies and allelic frequencies of TRPM2 SNP rs1556314 was observed between
      the survivors and fatal cases of septic patients (all P>0.05). Conclusion: The
      TRPM2 SNP rs1556314 does not have significant association with sepsis, but this
      result need to be confirmed by large scale studies.

PMID- 27868416
TI  - [Comparison of FibroTouch and acoustic radiation force impulse in diagnosis of
      liver fibrosis in patients with chronic hepatitis B].
AB  - Objective: To compare transient elastorgaphy (FibroTouch) and acoustic radiation
      force impulse (ARFI) in diagnosis of liver fibrosis in patients with chronic
      hepatitis B. Methods: One hundred and forty five patients with chronic hepatitis
      B underwent FibroTouch and ARFI examinations in Xixi Hospital of Hangzhou from
      January to November 2015. The liver stiffness (LSM) was detected by FibroTouch
      and the liver shear wave velocity (VTQ) was detected by ARFI; liver biopsy was
      performed in all patients. With biopsy results as gold standards, the diagnostic
      values of FibroTouch and ARFI for liver fibrosis were analyzed with Spearman
      correlation analysis and receiver operating characteristic (ROC) curve. Results:
      The correlation coefficient of FibroTouch and ARFI was 0.746 (P<0.01). FibroTouch
      and ARFI were significantly correlated with pathological stage determined by
      liver biopsy(r=0.705 and 0.727, all P<0.01). When 8.4 kPa was taken as the cut
      off value of LSM and 1.49 m/s was taken as the cut-off value of VTQ, the areas
      under ROC (AUCs) were 0.857 and 0.836 (P>0.05) in diagnosis of fibrosis S>=2
      stage; when 10.8 kPa of LSM and 1.49 m/s of VTQ were used as cut-off values, the
      AUCs were 0.872 and 0.881 (P>0.05) in diagnosis of S>=3 stage; when 12.3 kPa of
      LSM and 1.81m/s of VTQ were used as cut-off values, the AUCs were 0.875 and 0.888
      (P>0.05) in diagnosis of S=4 stage. Conclusion: Both FibroTouch and ARFI can be
      effectively used in evaluation of liver fibrosis in patients with chronic
      hepatitis B.

PMID- 27868417
TI  - [Evaluation of tear film and meibomian gland function in dry eye patients using
      Keratograph 5M].
AB  - Objective: To assess the application of Keratograph 5M in evaluating tear film
      and meibomian gland function in patients with dry eye. Methods: A total of 144
      eyes were recruited in the study, in which 72 eyes were from patients diagnosed
      with dry eye and 72 eyes were from healthy subjects. All subjects finished
      following tests or examinations:ocular surface disease index (OSDI) to evaluate
      eye symptoms; Keratograph 5M examination to obtain tear meniscus height (TMH),
      noninvasive tear break-up time (NIBUT) including first NIBUT (NIBUT-Fir) and
      average NIBUT (NIBUT-Ave), and infrared meibography; and fluorescein sodium
      staining to obtain fluorescein tearbreak-up time (FBUT). Results: Dry eye group
      had higher OSDI score than healthy control group, but its TMH, NIBUT-Fir and
      NIBUT-Ave were lower than those in healthy control group (all P<0.01). Total
      meiboscore in dry eye group was higher than that in healthy control group
      (P<0.01), and it showed a significant correlation with NIBUT-Fir and NIBUT-Ave
      (r=-0.449 and -0.398, P<0.01), but no correlation with ages was observed
      (r=0.031, P>0.05). The NIBUT-Fir and NIBUT-Ave showed a significant correlation
      with FBUT (r=0.833 and 0.727, P<0.01). Conclusion: Keratograph 5M is a
      convenient, accurate and non-invasive method to assess the function of tear film
      and meibomian gland, and the new meibography scoring system can evaluate the
      function of meibomian gland objectively and succinctly.

PMID- 27868418
TI  - [Fibromyalgia syndrome after comprehensive treatment of breast cancer: a case
      report].
AB  - Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and
      seldom reported. Here we present a case of a 50-year-old female patient,who was
      admitted to the hospital because of generalized fibromyalgia for 3 months and
      brain metastasis after the right breast carcinoma surgery for 1 month, and the
      clinical diagnosis was brain metastasis from breast carcinoma combined with
      fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic
      treatment but the patient eventually died of tumor progression.

PMID- 27868419
TI  - [Research progress on pharmacotherapy of calcific aortic valve disease].
AB  - With the population aging and declining incidence of rheumatic heart disease,
      calcific aortic valve disease (CAVD) has become the most frequent valve disease
      and the common cause of aortic valve replacement. Patients with CAVD need to cope
      with a deteriorating quality of life and valve replacement is the only effective
      clinical option for the patients. Therefore, early pharmacotherapy is of great
      significance in prevention or slow-down of the progression of CAVD. For years
      CAVD was considered to be a passive wear and tear process of valves, but now it
      is recognized as an active and multi-factorial process. Histopathologic studies
      have revealed that inflammation, disorder of calcium and phosphorus metabolism
      and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD
      pharmacotherapy have been carried out based on those histopathologic studies.
      Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied
      in recent years. This article reviews the recent research progress of the
      pharmacotherapy for CAVD.

PMID- 27868420
TI  - [Research progress on the role of epithelial-mesenchymal transition in
      pathogenesis of endometriosis].
AB  - Epithelial-mesenchymal transition plays an important role in the development and
      progression of endometriosis. Mesenchymal-epithelial transition is involved in
      forming localized lesions of endometriosis, while EMT is involved in the injury,
      repair and fibrosis induced by local inflammation of endometriosis and the
      process of cell invasion and metastasis. The studies of signal transduction
      pathway and related proteins of epithelial-mesenchymal transition in the process
      of endometriosis may provide new targets for diagnosis and treatment of
      endometriosis.

PMID- 27868422
TI  - "Neurobehavioral markers of resilience to depression amongst adolescents exposed
      to child abuse": Correction to Dennison et al. (2016).
AB  - Reports an error in "Neurobehavioral markers of resilience to depression amongst
      adolescents exposed to child abuse" by Meg J. Dennison, Margaret A. Sheridan,
      Daniel S. Busso, Jessica L. Jenness, Matthew Peverill, Maya L. Rosen and Katie A.
      McLaughlin (Journal of Abnormal Psychology, 2016[Nov], Vol 125[8], 1201-1212). In
      the article there was an error in the title. The word "Adolescents" was singular.
      The online version of this article has been corrected. (The following abstract of
      the original article appeared in record 2016-52992-014.) Childhood maltreatment
      is strongly associated with depression, which is characterized by reduced
      reactivity to reward. Identifying factors that mitigate risk for depression in
      maltreated children is important for understanding etiological links between
      maltreatment and depression as well as improving early intervention and
      prevention. We examine whether high reward reactivity at behavioral and
      neurobiological levels is a marker of resilience to depressive symptomology in
      adolescence following childhood maltreatment. A sample of 59 adolescents (21 with
      a history of maltreatment; Mean Age = 16.95 years, SD = 1.44) completed an fMRI
      task involving passive viewing of emotional stimuli. BOLD signal changes to
      positive relative to neutral images were extracted in basal ganglia regions of
      interest. Participants also completed a behavioral reward-processing task outside
      the scanner. Depression symptoms were assessed at the time of the MRI and again 2
      years later. Greater reward reactivity across behavioral and neurobiological
      measures moderated the association of maltreatment with baseline depression.
      Specifically, faster reaction time (RT) to cues paired with monetary reward
      relative to those unpaired with reward and greater BOLD signal in the left
      pallidum was associated with lower depression symptoms in maltreated youth.
      Longitudinally, greater BOLD signal in the left putamen moderated change in
      depression scores over time, such that higher levels of reward response were
      associated with lower increases in depression over time among maltreated youths.
      Reactivity to monetary reward and positive social images, at both behavioral and
      neurobiological levels, is a potential marker of resilience to depression among
      adolescents exposed to maltreatment. These findings add to a growing body of work
      highlighting individual differences in reactivity to reward as a core
      neurodevelopmental mechanism in the etiology of depression. (PsycINFO Database
      Record

PMID- 27868424
TI  - Increased cooperative behavior across remitted bipolar I disorder and major
      depression: Insights utilizing a behavioral economic trust game.
AB  - Mood disorders impact social functioning, but might contribute to experiences
      like affective distress-that might result in increased cooperative behavior under
      certain circumstances. We recruited participants with a history of bipolar I
      disorder (n = 28), major depressive disorder (n = 30), and healthy controls (n =
      27)-to play a well-validated behavioral economic Trust Game, a task that provides
      a well-controlled experimental scenario, to measure cooperative behavior for the
      first time across both groups. Both remitted mood-disordered groups cooperated
      significantly more than the control group, but did not differ from one another.
      These results suggest that, in some contexts, a history of mood disturbance can
      produce enhanced cooperation, even in the absence of current mood symptoms. We
      discuss the clinical significance of enhanced cooperation in mood disorders and
      point to key directions for future research. (PsycINFO Database Record

PMID- 27868425
TI  - Real-time simulation of hand motion for prosthesis control.
AB  - Individuals with hand amputation suffer substantial loss of independence.
      Performance of sophisticated prostheses is limited by the ability to control
      them. To achieve natural and simultaneous control of all wrist and hand motions,
      we propose to use real-time biomechanical simulation to map between residual EMG
      and motions of the intact hand. Here we describe a musculoskeletal model of the
      hand using only extrinsic muscles to determine whether real-time performance is
      possible. Simulation is 1.3 times faster than real time, but the model is locally
      unstable. Methods are discussed to increase stability and make this approach
      suitable for prosthesis control.

PMID- 27868421
TI  - Sex moderates the impact of birth weight on child externalizing psychopathology.
AB  - Low birth weight (LBW) has consistently been associated with childhood attention
      deficit/hyperactivity disorder (ADHD), and a similar association has been found
      for childhood externalizing disorders, such as oppositional defiant disorder
      (ODD) and conduct disorder (CD), albeit to a lesser degree. Although the
      association between LBW and these disorders has been robustly replicated, few
      studies have adequately controlled for confounding variables, such as parental
      age at birth and prenatal tobacco use, examined the specificity of the risk of
      LBW for ADHD symptoms, or investigated potential nonlinear (i.e., quadratic)
      effects of birth weight (BW). Additionally, the extent to which LBW confers risk
      for these disorders depending on childhood sex has rarely been examined. The
      current study examined associations between BW and ADHD, ODD, and CD symptom
      dimensions as well as the extent to which such associations are moderated by
      child sex, while also controlling for confounding variables. Significant
      interactions between sex and BW emerged across all analyses predicting ADHD and
      externalizing psychopathology, such that associations were stronger in males
      relative to females. Results remained when controlling for a number of confounds,
      including parental age, prenatal tobacco use, comorbid psychopathology, as well
      as other indicators of maternal and child health during the pre- and perinatal
      period. Both linear and quadratic associations emerged between BW and both
      hyperactivity and CD symptoms, whereas BW predicted inattention and ODD symptoms
      in a linear fashion. Future research should continue to investigate the impact of
      BW on ADHD and externalizing psychopathology, in particular, the biological
      mechanisms underlying this association. (PsycINFO Database Record

PMID- 27868423
TI  - Startle potentiation to uncertain threat as a psychophysiological indicator of
      fear-based psychopathology: An examination across multiple internalizing
      disorders.
AB  - Heightened reactivity to uncertain threat (U-threat) is an important individual
      difference factor that may characterize fear-based internalizing
      psychopathologies (IPs) and distinguish them from distress/misery IPs. To date,
      however, the majority of existing research examining reactivity to U-threat has
      been within individuals with panic disorder and major depressive disorder (MDD)
      and no prior study has directly tested this hypothesis across multiple IPs. The
      current study therefore explored whether heightened reactivity to U-threat is a
      psychophysiological indicator of fear-based psychopathology across 5 groups:
      current (a) social anxiety disorder (SAD); (b) specific phobia (SP); (c)
      generalized anxiety disorder (GAD); (d) MDD; and (c) individuals with no history
      of psychopathology (controls). All 160 adults completed a well-validated threat
      of-shock task designed to probe responses to predictable (P-) and U-threat.
      Startle eyeblink potentiation was recorded as an index of aversive arousal.
      Results indicated that individuals with SAD and SP evidenced greater startle
      potentiation to U-threat, but not P-threat, relative to individuals with GAD,
      MDD, and controls (who did not differ). The current findings, along with the
      prior panic disorder and MDD literature, suggest that heightened reactivity to U
      threat is a psychophysiological indicator of fear-based disorders and could
      represent a neurobiological organizing principle for internalizing
      psychopathology. The findings also suggest that individuals with fear disorders
      generally display a hypersensitivity to uncertain aversive events, which could
      contribute to their psychopathology. (PsycINFO Database Record

PMID- 27868426
TI  - Effects of regular Tai Chi practice and jogging on neuromuscular reaction during
      lateral postural control in older people.
AB  - This study examined the effects of regular Tai Chi practice and jogging on the
      neuromuscular activity of the trunk, hip, and ankle joint muscles of older people
      during lateral postural perturbation. A total of 42 older people participated in
      the study and formed the Tai Chi, jogging, and sedentary control groups.
      Electromyography signals were collected from the peroneus longus, anterior
      tibialis, gluteus medius, and erector spinae during unpredictable mediolateral
      perturbation. The Tai Chi group exhibited significantly faster latencies of the
      tibialis anterior and erector spinae than the control group. The jogging group
      showed a significantly shorter neuromuscular reaction time of the erector spinae
      than the control group. No significant difference was observed between the Tai
      Chi and jogging groups. Long-term regular Tai Chi practice enhanced the
      neuromuscular reaction of the erector spinae and tibialis anterior to lateral
      perturbation and will help timely posture correction when lateral postural
      distributions occur.

PMID- 27868428
TI  - Reflections from Fellows of ISAAC.

PMID- 27868427
TI  - Influence of shoe midsole hardness on plantar pressure distribution in four
      basketball-related movements.
AB  - This study examined how shoe midsole hardness influenced plantar pressure in
      basketball-related movements. Twenty male university basketball players wore
      customized shoes with hard and soft midsoles (60 and 50 Shore C) to perform four
      movements: running, maximal forward sprinting, maximal 45 degrees  cutting and
      lay-up. Plantar loading was recorded using an in-shoe pressure measuring system,
      with peak pressure (PP) and pressure time integral (PTI) extracted from 10
      plantar regions. Compared with hard shoes, subjects exhibited lower PP in one or
      more plantar regions when wearing the soft shoes across all tested movements (Ps
      < 0.05). Lower PTI was also observed in the hallux for 45 degrees  cutting, and
      the toes and forefoot regions during the first step of lay-up in the soft shoe
      condition (Ps < 0.05). In conclusion, using a softer midsole in the forefoot
      region may be a plausible remedy to reduce the high plantar loading experienced
      by basketball players.

PMID- 27868429
TI  - A new cerebroside and the cytotoxic constituents isolated from Xylaria
      allantoidea SWUF76.
AB  - A new cerebroside, namely allantoside (1), and 10 known compounds (2-11) were
      isolated from Xylaria allantoidea SWUF76. The structure of compound 1 was
      determined by comprehensive spectroscopic analysis including 1D and 2D nuclear
      magnetic resonance (NMR) as well as high-resolution electron ionisation mass
      spectrometry (HREIMS) and electrospray ionisation mass spectrometry (ESIMS).
      Compounds 1, 4, 5, 6, 7, 8 and 11 were evaluated for cytotoxic activities against
      cancer cell lines (Hela, HT29, HCT116 and MCF-7) and normal Vero cell lines by
      MTT assay. Compounds 6 and 7 exhibited anticancer activity after 24 h of
      treatment. Compound 7 showed significant cytotoxicity against Hela (IC50 = 2.24
      MUg/mL), HT29 (IC50 = 2.51 MUg/mL), HCT116 (IC50 = 3.50 MUg/mL) and MCF-7 (IC50 =
      3.77 MUg/mL) and Vero (IC50:3.65 MUg/mL) cells. Compound 6 showed slight
      cytotoxicity against all tested cancer cell lines.

PMID- 27868431
TI  - Tracking changes in glenohumeral joint position in acute post-stroke hemiparetic
      patients: an observational study.
AB  - AIMS: The majority of people develop hemiparetic shoulder inferior subluxation
      following stroke, but the timing of onset is unknown. This study aimed to assess
      changes in glenohumeral joint centre of rotation (GHJC) during the first six
      weeks following stroke. METHODS: Thirty patients with confirmed diagnosis of
      stroke (age 65 +/- 19 years, 60% female, 40% right side affected) were assessed
      within 14 days of admission and at six weeks along with matched controls.
      Bilateral GHJC was determined using a three-dimensional electromagnetic tracking
      device (ETD). RESULTS: At baseline, GHJC in the stroke group was positioned
      posteriorly on the hemiparetic side compared to the non-hemiparetic side (mean
      difference -4.0, 95% confidence interval (CI) - 7.7 to -3.0 mm). In matched
      controls, GHJC was positioned anterior to the acromion with no significant
      difference between limbs. At six weeks, the only significant difference occurred
      for the stroke group; non-hemiparetic GHJC was positioned 12.3 mm (95% CI 2.5
      22.1) closer to the acromion compared with control group. CONCLUSION: Minimal
      changes in glenohumeral joint positioning occurs early post-stroke. Clinicians
      should consider changes in glenohumeral joint position for both non- and
      hemiparetic sides during the early rehabilitation phase following stroke.
      Implications for rehabilitation Changes occur in glenohumeral joint centre of
      rotation (GHJC) position between hemiparetic and non-hemiparetic sides early in
      people with mild stroke. Clinicians need to be aware of early GHJC positional
      changes. Early GHJC positional changes may contribute to the development of
      hemiparetic shoulder pain (HSP), anterior humeral subluxation and glenohumeral
      joint impingement. Clinicians should employ current best practice guidelines
      which promote safe positioning and handling of the upper limb to minimise
      subluxation forces and potential trauma to the passive restraints of the shoulder
      in the acute phase following stroke, to reduce the possibility of glenohumeral
      subluxation in the short term.

PMID- 27868430
TI  - A new oleanolic-type triterpene glycoside from Anchusa italica.
AB  - A new oleanolic-type triterpene glycoside, (3beta,21beta)-21-[(beta-d
      glucopyranosyl-(1->2)-beta-d-glucopyranosyl)oxy]-3-hydroxyolean-12-en-28-oic acid
      (1), together with five analogues, oleanazuroside 1 (2), oleanazuroside 2 (3), 24
      hydroxytormentic acid ester glucoside (4), 24-epi-pinfaensin (5), and oleanolic
      acid 3-O-alpha-l-arabinoside (6) were isolated from the n-butyl alcohol extract
      of Anchusa italica. Their structures were determined spectroscopically and
      compared with previously reported spectral data. Compounds 3-4 and 6 were
      evaluated for their cytotoxic activities against five human cancer cell lines,
      but only compound 6 showed moderate cytotoxicity.

PMID- 27868432
TI  - A criterion-referenced assessment is needed for measuring child obesity.
AB  - Body Mass Index (BMI), as an adiposity indicator, assumes that for any given
      height a change in weight is attributed to a change in fat. This seems
      problematic in growing youth as great divergence is evident in bone, muscle, and
      adipose tissue development. Secondly, use of reference populations in
      categorizing children based on BMI, frequently use arbitrary percentile cut-offs
      for obesity and do not meet all of the assumptions that cut-offs imply. Lastly,
      BMI does not control for maturation status. Criterion-referenced assessments of
      child obesity that account for abdominal adiposity and permit international
      comparisons, such as waist-to-height ratio (WtHR), must be considered. Better
      predictive utility has been demonstrated when using WtHR for abdominal adiposity
      and cardiovascular risk factors in youth compared with BMI. Although multiple
      methods for assessing waist circumference may be problematic for comparison
      purposes, its simplicity and international comparability aspects make it a
      promising alternative to BMI.

PMID- 27868433
TI  - Performance trends in 3000 m open-water age group swimmers from 25 to 89 years
      competing in the FINA World Championships from 1992 to 2014.
AB  - We investigated trends in participation, performance and sex difference in
      performance in 3000 m freestyle in age groups swimmers (25-29 to 85-89 years)
      competing in the Federation Internationale de Natation World Masters
      Championships between 1992 and 2014. During this period, participation increased
      in women and men. Women and men improved race times across years in all age
      groups. Women were slower in age groups 25-29 to 70-74 years. In age groups 75-79
      and 85-89 years, however, race times were similar for both women and men. Sex
      difference in performance remained unchanged across years. In summary,
      performance improved across years in all age groups, men were faster than women
      up to the age group 70-74 years and women were not able to reduce the sex
      difference in performance to men across years. For athletes and coaches, an
      increase in participation and a continuous improvement in performance can be
      expected in these age group athletes.

PMID- 27868435
TI  - A touchy topic: tactile assessment among pediatric therapists.
AB  - PURPOSE: Tactile impairments affect over 77% of children with unilateral cerebral
      palsy (CP). This study aimed to examine the current practices of pediatric
      therapists in relation to tactile assessment and the barriers to carrying out
      tactile assessment in children with CP. METHOD: The study was in two parts. In
      part one, pediatric therapists (n = 35) completed a questionnaire detailing their
      current knowledge and the use of tactile assessments in children. In part two,
      therapists (n = 12) completed a questionnaire based on the Theoretical Domains
      Framework examining the barriers and facilitators to completing tactile
      assessments in clinical practice. RESULTS: Most therapists (over 90%) carry out
      tactile assessments in the minority (less than 25%) of children with CP that they
      treat. Therapists reported the need for improved knowledge/skills (n = 24) and
      confidence (n = 19) in carrying out tactile assessments, alongside the provision
      of necessary equipment (n = 17). Qualitative reports also suggested that
      organizational assessment guidelines and templates may facilitate the
      implementation of tactile assessment. CONCLUSIONS: A multi-faceted knowledge
      translation strategy to address the barriers to tactile assessment among
      pediatric therapists needs to be developed. Implications for rehabilitation
      Pediatric occupational therapists and physiotherapists may not be completing
      tactile assessments according to current evidence-based recommendations.
      Therapists identified five main barriers, including a lack of knowledge, skills,
      belief in their capabilities (confidence), behavioral regulation (organizational
      procedures), and environmental context (e.g., equipment). Therapists recommended
      several potential facilitators, including access to necessary equipment,
      procedures, record sheets, training in tactile assessments, and research
      supporting related interventions. Service providers are encouraged to develop
      multi-faceted knowledge translation strategies that address these barriers and
      maximize facilitators.

PMID- 27868434
TI  - Communication aid requirements of intensive care unit patients with transient
      speech loss.
AB  - Alert and transiently nonvocal intensive care unit (ICU) patients are dependent
      on augmentative and alternative communication (AAC). Unfortunately, the
      literature demonstrates that existent AAC devices have not been widely adopted,
      and unaided methods are often the primary modalities used despite being
      insufficient, and frustrating. We present the results of a qualitative semi
      structured interview study with 8 ex-ICU patients, 4 ICU patient relatives, and 6
      ICU staff, exploring their AAC needs and requirements. Participants identified
      important AAC hardware, software, and content requirements. Salient factors
      impacting on AAC adoption in the ICU setting were also highlighted and included
      the need for staff training and bedside patient assessment. Based on the study
      results, we propose a series of recommendations regarding the design and
      implementation of future AAC tools specifically targeted at this group.

PMID- 27868436
TI  - An oxovanadium(IV) complex protects murine bone marrow cells against cisplatin
      induced myelotoxicity and DNA damage.
AB  - Cisplatin (CDDP) is one of the first-line anticancer drugs that has gained
      widespread use against various forms of human malignancies. But, the therapeutic
      outcome of CDDP therapy is limited due to its adverse effects including
      myelotoxicity and DNA damage which may lead to the subsequent risk of developing
      secondary cancer. Hence, in search of a suitable cytoprotectant, this study
      investigated the probable protective efficacy of an oxovanadium(IV) complex,
      namely oxovanadium(IV)-L-cysteine methyl ester complex (VC-IV) against CDDP
      induced myelosuppression and genotoxic damage in the bone marrow cells of Swiss
      albino mice. CDDP was administered intraperitoneally (5 mg/kg b.w.) and VC-IV was
      administered orally (1 mg/kg b.w.) in concomitant and 7 d pretreatment schedule.
      Treatment with VC-IV in CDDP-treated mice significantly (p < 0.01) enhanced bone
      marrow cell proliferation and inhibited cell death in the bone marrow niche
      indicating improvement of CDDP-induced myelotoxicity. The organovanadium compound
      also significantly (p < 0.01) reduced the percentage of chromosomal aberrations,
      the frequency of micronuclei formation, and the extent of DNA damage. The
      observed chemoprotective effect of VC-IV was attributed to its anti-oxidant
      efficacy which significantly (p < 0.01) attenuated CDDP-induced generation of
      free radicals, and restored (p < 0.01) the levels of oxidized and reduced
      glutathione. Hence, VC-IV may serve as a promising candidate for future
      development to decrease the deleterious effects of CDDP in the bone marrow cells
      of cancer patients and associated secondary complications.

PMID- 27868437
TI  - Can we address depression in vision rehabilitation settings? Professionals'
      perspectives on the barriers to integrating problem-solving treatment.
AB  - PURPOSE: Low vision rehabilitation (LVR) is a pertinent context for integrating
      early, evidence-based psychological interventions given the high prevalence of
      untreated depression in adults with vision impairment. This study aims to
      identify the perceived barriers and facilitators to staff-delivered telephone
      based problem-solving treatment for primary care (PST-PC) offered as an
      integrated component of LVR. METHODS: Qualitative semi-structured interviews,
      developed using the theoretical domains framework (TDF) and Consolidated
      Framework for Implementation Research (CFIR), were conducted with 21 LVR
      professionals and a clinical psychologist involved in the delivery of PST-PC.
      Barriers and facilitators at the practitioner, client, intervention, and
      organizational level were identified with thematic analysis using a "theoretical"
      approach. RESULTS: Prominent barriers were a lack of role recognition for PST-PC
      practitioners (n = 32), unmet client expectation with PST-PC (n = 28),
      dissatisfaction with telephone delivery (n = 27), and limited organizational
      awareness of PST-PC (n = 39). Facilitating factors included a recognized need for
      evidence-based psychological services (n = 28), clients experiencing benefits in
      early sessions (n = 38), PST-PC promoting practical skills (n = 26), and
      comprehensive PST-PC training (n = 36). CONCLUSIONS: PST-PC may provide an
      accessible early intervention for LVR clients with depressive symptoms. Ongoing
      practitioner training, clinical support, and screening potential LVR clients for
      treatment suitability are likely to enhance delivery in this setting.
      Implications for rehabilitation Depression is highly prevalent in adults engaged
      in low vision rehabilitation (LVR) programs, yet few receive support. Clinical
      guidelines recommend integrated models of care be offered within rehabilitation
      settings as early intervention for mild to moderate levels of depressive
      symptoms. Integrated telephone-based problem-solving treatment for primary care
      (PST-PC) delivered by trained LVR practitioners is a practical, skills-based
      model that has potential to increase access to an early psychological
      intervention in LVR clients with depressive symptoms. LVR clients are often older
      in age, have multiple comorbid health conditions and a significant level of
      functional disability, requiring flexibility in the delivery of PST-PC and
      specialized staff training, and support in working with older and more complex
      clients.

PMID- 27868438
TI  - A standardized review of smartphone applications to promote balance for older
      adults.
AB  - BACKGROUND: Balance is one of the risk factors for falls in older adults. The use
      of smartphone applications (apps) related to health (mHealth) is increasing and,
      while there is potential for apps to be used as a self-managed balance
      intervention, many healthcare providers are concerned about the content and
      credibility of mHealth apps overall. PURPOSE: This study evaluates the quality of
      balance promoting apps and identifies strengths and areas of concern to assist
      healthcare providers in recommending these resources. MATERIALS AND METHODS:
      Balance apps for the general public, offered on the iPhone Operating System (iOS)
      and Android platforms, were evaluated using the Mobile Application Rating Scale
      (MARS). RESULTS: Five iOS apps met the inclusion criteria. The mean scores for
      each of the domains in MARS were: Engagement (3.32), Information (3.7),
      Functionality (3.8), and Esthetics (3.8). Overall, one app (UStabilize) received
      a rating of 4.43 in MARS five-point scale, which was considered "good". Other
      apps in the review demonstrated acceptable quality. CONCLUSIONS: The reviewed
      balance apps targeted to improve or maintain physical balance were of acceptable
      quality. Apps address many current issues older adults have to accessing
      rehabilitation services and, as such, may be particularly useful for this group.
      Future research should focus on assessing and comparing app efficacy. Development
      of balance apps for the Android platform is also necessary. Implications for
      Rehabilitation Given the availability and accessibility of various mHealth apps
      and the increasing mobile device usage among older adults, mobile apps are a
      promising avenue for delivering rehabilitation interventions, such as balance
      training, to older adults. Smartphone apps exist for balance training but overall
      confidence in health apps within the healthcare community is low and rigorous
      evaluation is required. A range of apps exist that demonstrate acceptable to good
      quality and stakeholders should work towards having these apps listed in credible
      mHealth clearinghouses.

PMID- 27868439
TI  - [The treatment of walled-off pancreatic necrosis. Review].
AB  - : Walled-off pancreatic necrosis is a late complication of severe acute
      pancreatitis that generally needs some interventions. The aim of this review is
      to analyse the indications, technical aspects and limits of these therapeutic
      options. The development of the walled-off pancreatic necrosis needs 4-6 weeks
      from the onset of the disease. The necrosectomy is recommended after this time.
      Endoscopic necrosectomy offers good results if the necrosis is in retrogastric or
      retroduodenal localisations. Open necrosectomy can be performed through the
      gastrocolic ligament or the mesocolon. It is suggested to complete necrosectomy
      with open or closed omental bursa drainage or packing. The transgastric
      necrosectomy does not need external drainage. Surgical procedures can be
      performed with laparoscopy either. In localized necrosis other minimal invasive
      approaches can be used. CONCLUSIONS: In addition to the transluminal endoscopic
      or minimal invasive necrosectomies different types of surgical procedures has an
      important role in the treatment of walled-off pancreatic necrosis. Orv. Hetil.,
      2016, 157(47), 1866-1870.

PMID- 27868441
TI  - [Evaluation of free radical quantity in the anterior chamber following
      femtosecond laser-assisted capsulotomy].
AB  - INTRODUCTION: Femtosecond laser is a revolutionary, innovative treatment method
      used in cataract surgery. AIM: To evaluate free radical quantity in the anterior
      chamber of the eye, during femtosecond laser assisted capsulotomy, in a porcine
      eye model. METHOD: Seventy fresh porcine eyes were collected within 2 hours post
      mortem, were transported at 4 oC and treated within 7 hours. Thirty-five eyes
      were used as control and 35 as femtosecond laser assisted capsulotomy group. A
      simple luminol-dependent chemiluminescence method was used to measure the total
      scavenger capacity in the aqueous humour, as an indicator of free radical
      production. The emitted photons were expressed in relative light unit %. RESULTS:
      The relative light unit % was lower in the control group (median 1%,
      interquartile range [0.4-3%]) than in the femtosecond laser assisted capsulotomy
      group (median 4.4%, interquartile range [1.5%-21%]) (p = 0.01). CONCLUSIONS:
      Femtosecond laser assisted capsulotomy decreases the antioxidant defense of the
      anterior chamber, which refers to a significant free radical production during
      femtosecond laser assisted capsulotomy. Orv. Hetil., 2016, 157(47), 1880-1883.

PMID- 27868440
TI  - [Maximizing nodal yield while minimizing surgical morbidity: the appropriate neck
      dissection].
AB  - Cervical regional lymphadenectomy, also known as neck dissection, is a
      fundamental procedure in head and neck surgery. Its evolution over 110 years
      resulted in a great deal of confusion in the literature and in clinical practice,
      due to the heterogenicity in training, classification and surgical techniques,
      which makes outcomes comparability virtually impossible. The authors aim to
      clarify this situation in a structured manner, in order to facilitate
      communication among all specialists involved in multidisciplinary head and neck
      cancer care. The ultimate goal is to make sure that each and every head and neck
      cancer patient receives their optimal treatment. Review of the history and
      literature with statistical comparison of the two mainstraim methods regarding
      their nodal yield results. The applied surgical technique has a significant
      impact on nodal yield. An appropriate surgical concept achieves maximum oncologic
      benefit, minimum surgical morbidity with optimized adjuvant indications. Orv.
      Hetil., 2016, 157(47), 1871-1879.

PMID- 27868442
TI  - [HIV/AIDS and law in Hungary].
AB  - INTRODUCTION: The legal aspects of HIV/AIDS are mirrored by the statistical data.
      AIM: The aim of the author is to show the effect of HIV/AIDS on today's Hungarian
      society. METHOD: Analysis of data issued by the National Center for Epidemiology
      in Hungary and those to be found in the professional literature, as well as
      analysis of the Hungarian legal practice. RESULTS: Hungarian courts tend to
      impose a lighter punishment on a perpetrator diagnosed with AIDS than on a
      healthy perpetrator. According to the data issued by the Hungarian
      Epidemiological Center, in 1985, 16 HIV-contaminated persons were registered in
      Hungary; in 1995, 81, in 2005, 107, whilst in 2015, 201 HIV-contaminated persons
      were registered in Hungary. In 2005, 10 of the 107 HIV-contaminated persons were
      anonymous, whilst, in 2015, 37 of the 201 HIV-contaminated persons were
      anonymous. According to the known data of not anonymous HIV-contaminated persons,
      the number of males predominates largely over the number of females and this has
      been the case during the past decades. In Hungary, only a small proportion of the
      HIV-contaminated persons have died: the number of males predominates over the
      number of females. CONCLUSIONS: As to HIV/AIDS, latency poses problems in the
      field of healthcare prevention and legal prevention. It seems to be important to
      protect data relating to healthcare, though the data protection should not impede
      the prevention of HIV/AIDS. Orv. Hetil., 2016, 157(47), 1884-1890.

PMID- 27868444
TI  - [Plant-based diets: a review].
AB  - Plant-based diet is an old-new trend in nutrition. In this review based on a
      historical context, we wish to introduce this popular nutritional trend. Our aim
      is to present plant-based diet as a primary measure for prevention. We intend to
      critically analyse some past stereotypes related to plant-based diet - whose main
      components include fruits, vegetables, whole grains, legumes, nuts and seeds -
      according to the literature (e.g. protein, vitamin B12, folic acid, and iron
      intake) by doing so we wish to create an adequate conceptual basis for its
      interpretation. We discuss positive physiological effects of plant-based diet and
      its possible role in diseases risk reduction. Cardiovascular and metabolic
      diseases developing due to obesity could be prevented by a properly compiled
      plant-based diet. For patients with cancer minimizing the intake of foods of
      animal origin - as opposed to plant-based ones - has proved to have positive
      effects. Our review suggests this diet can be used in a number of diseases and it
      also provides long-term sustainable solutions for the health care challenges of
      the newest era. Orv. Hetil., 2016, 157(47), 1859-1865.

PMID- 27868445
TI  - Acetone and methanol fruit extracts of Terminalia paniculata inhibit HIV-1
      infection in vitro.
AB  - In this study, we report the in vitro anti-HIV1 activity of acetone and methanol
      extracts of fruit of Terminalia paniculata. Cytotoxicity tests were conducted on
      TZM-bl cells and peripheral blood mononuclear cells (PBMC), the CC50 values of
      both the extracts were >=260 MUg/mL. Using TZM-bl cells, the extracts were tested
      for their ability to inhibit replication of two primary isolates HIV-1 (X4,
      Subtype D) and HIV-1 (R5, Subtype C). The activity against HIV-1 primary isolate
      (R5, Subtype C) was confirmed using activated PBMC and by quantification of HIV-1
      p24 antigen. Both the extracts showed anti-HIV1 activity in a dose-dependent
      manner. The EC50 values of the acetone and methanol extracts of T. paniculata
      were <=10.3 MUg/mL. The enzymatic assays were performed to determine the
      mechanism of action which indicated that the anti-HIV1 activity might be due to
      inhibition of reverse transcriptase (>=77.7% inhibition) and protease (>=69.9%
      inhibition) enzymes.

PMID- 27868447
TI  - Advancing Knowledge About Suicide Prevention Media Campaigns.

PMID- 27868448
TI  - Applying an ecological framework to understand transition pathways to post
      secondary education for youth with physical disabilities.
AB  - PURPOSE: The purpose of this study was to explore the experiences of youth with
      physical disabilities and clinicians who support them in their transition to post
      secondary education (PSE). Most research on transition to PSE has focused on
      youth with intellectual disabilities while there is a lack of research on youth
      with physical disabilities. METHODS: This study drew on 30 interviews with 20
      youth with disabilities and 10 clinicians. We used Bronfrenbrenner's ecological
      framework to inform our analysis. RESULTS: Our results showed that there are
      several important individual skills that youth need to be successful in
      transitioning to PSE. Youth with disabilities experienced supports from peers and
      family that influence their transition to PSE. Several disability-specific issues
      (e.g., coping, self-care, disclosure, and accommodations) were often a barrier to
      transitioning to PSE. Clinicians and youth both reported that improved inter
      professional collaboration and inter-agency partnerships were needed to enhance
      the transition experience. Societal attitudes (stigma and discrimination),
      policies, and the timing of transitions also influence youth's transition.
      CONCLUSION: Applying an ecological approach helped to provide a more holistic
      perspective of the PSE transitions and emphasizes the need to consider more than
      just preparing individuals but also where they are transitioned. Implications for
      rehabilitation Clinicians and educators should continue to promote the
      development of relevant life skills (e.g., self-advocacy, disclosure, and
      navigating public transportation) that youth need to succeed in post-secondary
      education. Clinicians should continue to educate and support youth regarding the
      process for disclosing their condition and how to request and set up
      accommodations in PSE. Clinicians should connect youth with disabilities to
      appropriate resources that can support them and continue to help them to set
      career goals and develop career plans. There is a critical need for improved
      inter-professional collaboration among clinicians providing transition services
      and inter-agency partnerships among high schools, disability organizations, and
      PSEs to enhance transition experiences for youth with disabilities.

PMID- 27868449
TI  - Establishing the Turkish version of the SIGAM mobility scale, and determining its
      validity and reliability in lower extremity amputees.
AB  - PURPOSE: The aim of this study is to adapt the Special Interest Group in Amputee
      Medicine (SIGAM) mobility scale to Turkish, and to test its validity and
      reliability in lower extremity amputees. MATERIAL AND METHODS: Adaptation of the
      scale into Turkish was performed by following the steps in American Association
      of Orthopedic Surgeons (AAOS) guideline. Turkish version of the scale was tested
      twice on 109 patients who had lower extremity amputations, at hours 0 and 72. The
      reliability of the Turkish version was tested for internal consistency and test
      retest reliability. Structural validity was tested using the "scale validity"
      method. For this purpose, the scores of the Short Form-36 (SF-36), Functional
      Ambulation Scale (FAS), Get Up and Go Test, and Satisfaction with the Prosthesis
      Questionnaire (SATPRO) were calculated, and analyzed using Spearman's correlation
      test. RESULTS: Cronbach's alpha coefficient was 0.67 for the Turkish version of
      the SIGAM mobility scale. Cohen's kappa coefficients were between 0.224 and
      0.999. Repeatability according to the results of the SIGAM mobility scale (grades
      A-F) was 0.822. We found significant and strong positive correlations of the
      SIGAM mobility scale results with the FAS, Get Up and Go Test, SATPRO, and all of
      the SF-36 subscales. CONCLUSION: In our study, the Turkish version of the SIGAM
      mobility scale was found as a reliable, valid, and easy to use scale in everyday
      practice for measuring mobility in lower extremity amputees. Implications for
      Rehabilitation Amputation is the surgical removal of a severely injured and
      nonfunctional extremity, at a level of one or more bones proximal to the body.
      Loss of a lower extremity is one of the most important conditions that cause
      functional disability. The Special Interest Group in Amputee Medicine (SIGAM)
      mobility scale contains 21 questions that evaluate the mobility of lower
      extremity amputees. Lack of a specific Turkish scale that evaluates
      rehabilitation results and mobility of lower extremity amputees, and determines
      their needs, directed us to perform a study on this topic when we took the number
      of amputations performed in our country into consideration. SIGAM mobility scale
      is directed at rehabilitation specialists who are working in amputee medicine.
      Turkish version of this scale was found both reliable and valid in our study and
      hence it can be used in clinical practice and studies.

PMID- 27868450
TI  - Pharmacological management of diabetic dyslipidemia.
AB  - INTRODUCTION: Diabetes mellitus is associated with increased cardiovascular
      disease (CVD) risk. Areas covered: Main goal of hypolipidemic treatment in
      diabetic patients is low-density lipoprotein cholesterol (LDL-C) lowering with
      the use of statins. Addition of ezetimibe is useful in diabetic patients who
      cannot achieve their LDL-C target. However, many diabetic patients have increased
      residual CVD risk, which is mainly attributed to high triglycerides and low high
      density lipoprotein (HDL-C) values. The addition of fenofibrate targets these
      variables and possibly reduces residual CVD risk, but a possible beneficial
      effect has been shown only in a pre-specified subgroup analysis in patients with
      high triglycerides and low HDL-C values. The newer proprotein convertase
      subtilisin/kexin type 9 inhibitors lower substantially LDL-C levels, but data
      from specifically designed trials in diabetic patients are not currently
      available. Although the cholesterol ester transfer protein (CETP) inhibitors have
      shown harmful effects or lack of efficacy in completed clinical trials, the newer
      CETP inhibitors have promising effects on lipid profile and carbohydrate
      metabolism, but their effects on CVD risk and safety profile have not been
      assessed. Expert commentary: Clinicians have a range of pharmacological options
      to reduce the CVD risk of diabetic patients.

PMID- 27868451
TI  - Take-home experience of overseas doctors at the end of their two years training
      placements in the International Doctors Training Programme in Obstetrics and
      Gynaecology in the United Kingdom: A questionnaire-based study.
AB  - This was a questionnaire-based study of overseas doctors, who came to the United
      Kingdom through the International Doctors Training Programme (IDTP) of Obstetrics
      and Gynaecology during the period of 2009-2012. The study was conducted at the
      end of their two-years training placement to find out what went well, what did
      not go well, where problems were encountered, and how they could have been
      avoided. We traced 48 overseas doctors, 35 (73%) responded to our questionnaire.
      Only 30% (9) felt that less than 50% of their expectations were met during their
      training period, 73.3% (22) of them received adequate help and support from their
      supervisors and 83.3% (25) would recommend IDTP to their colleagues. In
      conclusion, identification of the educational needs of international trainees,
      establishing a framework for their effective supervision and streamlining their
      training programme, in collaboration with the Royal College, regional deaneries
      and hosting hospitals are essential pre-requisites for overseas doctors to get
      the most out of their training.

PMID- 27868452
TI  - Closed reduction of zygomatic tripod fractures using a towel clip.
AB  - BACKGROUND: The zygomatic bone constitutes the prominence of the cheek. Fractures
      of the zygomatic bone are the second most treatment of zygomatic bone fractures
      and can be examined under two headings, open and closed reductions. This paper
      describes a new technique in the closed reduction of tripod fractures using a
      towel clip. METHODS: Seventeen consecutive patients (three females, 14 males)
      with a mean age of 35.5 years (range = 18-66 years) with zygomatic tripod
      fracture were treated using the towel clip technique between December 2011 and
      February 2014. RESULTS: Patients were assessed in the first and 6 months
      postoperatively, by physical examination and computed tomography. Preoperatively,
      nine patients had paresthesia in the infraorbital nerve region. Three of these
      cases regressed postoperatively. Persistent collapse of the zygomatic projection
      was present in one patient. CONCLUSION: Non-comminuted zygomatic tripod fractures
      can be easily treated percutaneously with the towel clip method in the absence of
      preoperative ocular problems such as diplopia, enophthalmos, or restricted eye
      movements. The technique is economical, fast, and safe. The possibility of
      persistent zygoma collapse after reduction should be kept in mind, and
      preoperatively the team should be warned of the possibility of progression to
      open reduction during surgery.

PMID- 27868453
TI  - Can body mass index predict the outcome of diffuse large B-cell lymphoma? A
      single-center retrospective study in China.
AB  - We carried out a single-center retrospective study to assess the predictive value
      of body mass index (BMI) in the outcome of Chinese patients with diffuse large B
      cell lymphoma (DLBCL). 143 eligible patients were enrolled between January 2008
      and May 2015. These patients were stratified into two groups, 74 patients in low
      BMI group (BMI <23.0 kg/m2) and 69 patients in high BMI group (BMI >=23.0 kg/m2).
      We compared the baseline characteristics, primary response, and survival outcome
      in two groups. Well-known influence factors were similar between the two groups,
      while gender was not (p = .023) but did not act as a risk factor. No association
      between BMI and primary response was observed. Patients with high BMI were
      inclined to have better overall survival (OS) (p = .018), but we didn't find an
      association in progression-free survival (PFS) (p = .067). We also found a sex
      dependent effect of BMI on OS, with high BMI increased OS in female patients (p =
      .027) but showed no correlation in male patients (p = .310).

PMID- 27868455
TI  - Identification of patients at risk for preeclampsia with the use of uterine
      artery Doppler velocimetry and copeptin.
AB  - PURPOSE: To investigate the relationship between maternal copeptin levels and
      uterine artery Doppler examination and progress of preeclampsia. MATERIALS AND
      METHODS: A cross-sectional study was designed with women those were screened at
      20 + 0 - 24+  6 weeks' gestation between May 2014 and August 2014. The obstetric
      records of all normotensive women were examined. Uterine artery Doppler
      velocimetry results and serum copeptin levels were measured. The patients were
      divided into two groups according to normal (n = 67) and abnormal uterine artery
      Doppler (n = 21) findings. RESULTS: Maternal age was significantly lower in group
      1 (n = 21, 23.9%) than in group 2 (n= 67, 76.1%) (p < 0.05). We found no
      differences in maternal characteristics, birth weight, gestational age at
      delivery and copeptin levels between the two groups. Maternal serum copeptin
      levels were higher in women who subsequently developed preeclampsia. There was
      also a significant correlation between copeptin levels and the presence of
      preeclampsia. (p = 0.002). CONCLUSIONS: Copeptin levels are significantly higher
      in patients who develop preeclampsia.

PMID- 27868456
TI  - Emergency peripartum hysterectomy: single center ten-year experience.
AB  - PURPOSE: The purpose of our study is to determine the incidence, risk factors,
      indications, outcomes, and complications of emergency peripartum hysterectomy
      (EPH) performed in a university hospital. METHODS: This retrospective study
      includes 54 cases of EPH performed at the department of obstetrics and gynecology
      of Gaziantep University Hospital between the years 2005-2015. We included all
      hysterectomy cases during the first 24 h after delivery beyond 20 weeks of
      gestation. We compared the most common indications of EPH between each other.
      RESULTS: There were 54 EPH out of 8922 deliveries with an incidence of 6.1 per
      1000 deliveries during the study period. The most common indication was abnormal
      placentation (74.0%). Urinary tract injury (33.4%) was the most common
      intraoperative complication. Bilateral hypogastric artery ligation, urinary tract
      injury, type of hysterectomy, post-op stay in the hospital, delivery in another
      hospital and other complications were significantly related to the type of EPH
      indication (p < 0.05). CONCLUSION: Abnormal placentation was the most common
      indication for EPH. Previous CS can be suggested as a high-risk factor for
      abnormal placentation. The delivery should be performed in appropriate clinical
      settings with experienced surgeons when high-risk factors like abnormal
      placentations are determined preoperatively.

PMID- 27868454
TI  - The ATP-sensitive K channel is seizure protective and required for effective
      dietary therapy in a model of mitochondrial encephalomyopathy.
AB  - Effective therapies are lacking for mitochondrial encephalomyopathies (MEs). MEs
      are devastating diseases that predominantly affect the energy-demanding tissues
      of the nervous system and muscle, causing symptoms such as seizures,
      cardiomyopathy, and neuro- and muscular degeneration. Even common anti-epileptic
      drugs which are frequently successful in ameliorating seizures in other diseases
      tend to have a lower success rate in ME, highlighting the need for novel drug
      targets, especially those that may couple metabolic sensitivity to neuronal
      excitability. Furthermore, alternative epilepsy therapies such as dietary
      modification are gaining in clinical popularity but have not been thoroughly
      studied in ME. Using the Drosophila ATP61 model of ME, we have studied dietary
      therapy throughout disease progression and found that it is highly effective
      against the seizures of ME, especially a high fat/ketogenic diet, and that the
      benefits are dependent upon a functional KATP channel complex. Further
      experiments with KATP show that it is seizure-protective in this model, and that
      pharmacological promotion of its open state also ameliorates seizures. These
      studies represent important steps forward in the development of novel therapies
      for a class of diseases that is notoriously difficult to treat, and lay the
      foundation for mechanistic studies of currently existing therapies in the context
      of metabolic disease.

PMID- 27868457
TI  - The Hillary Climber trumps manual testing: an automatic system for studying
      Drosophila climbing.
AB  - Climbing or negative geotaxis is an innate behavior of the fruit fly Drosophila
      melanogaster. There has been considerable interest in using this simple behavior
      to gain insights into the changes in brain function associated with aging,
      influence of drugs, mutated genes, and human neurological disorders. At present,
      most climbing tests are conducted manually and there is a lack of a simple and
      automatic device for repeatable and quantitative analysis of fly climbing
      behavior. Here we present an automatic fly climbing system, named the Hillary
      Climber (after Sir Edmund Hillary), that can replace the human manual tapping of
      vials with a mechanical tapping mechanism to provide more consistent force and
      reduce variability between the users and trials. Following tapping the HC records
      fly climbing, tracks the fly climbing path, and analyzes the velocity of
      individual flies and the percentage of successful climbers. The system is
      relatively simple to build, easy to operate, and efficient and reliable for
      climbing tests.

PMID- 27868459
TI  - The Institute of Medical Illustrators (IMI) Platinum Award 2016.

PMID- 27868458
TI  - Angiographic embolisation of a ruptured renal artery aneurysm in a primigravida
      during the first trimester.

PMID- 27868461
TI  - A new approach to feedback control of radiofrequency ablation systems for large
      coagulation zones.
AB  - AIM: The aim of this study was to investigate the feasibility of achieving
      relatively large coagulation zones (i.e. >=3 cm in diameter) with radiofrequency
      ablation (RFA) by using a broad control system. MATERIALS AND METHODS: A broad
      control system consists of information such as (i) the area of the tumour tissue
      for feedback control, (ii) the set-point temperature and (iii) the control law.
      The proposed approach has advanced knowledge in (i) and (ii) in particular. RFA
      is known to be limited by tissue dehydration that occurs around the electrode,
      which results in impedance such that no further energy can be delivered to the
      tissues. We proposed the notion of "energy gate", an area on the electrode, which
      is not covered by the dehydrated tissue and through which energy can still be
      delivered to the surrounding tissues. Given a specific size of energy gate, both
      (i) the area of the tissue in which the temperature is monitored and (ii) the set
      point temperature were determined. A reliable finite element model or simulator
      for a commercially available electrode was used and the tissue surrounding the
      RFA electrode was divided into three areas for a comprehensive study of the
      issues (i) and (ii). Porcine liver tissue (30 specimens in total) and a custom
      made RFA device with a RF power generator (100 W and 460 +/- 30 kHz) and a
      Covidien cool-tip electrode (17 gauge and 30 mm exposure) were used to validate
      the findings regarding the area of the tissue for feedback control and the set
      point temperature. RESULTS: The size of coagulation zone achieved was maximised
      when the area of tissue surrounding the middle part of the active tip (i.e. Point
      7) was used for feedback control and when the set-point temperature was set to 90
      ^ C (this temperature is determined based on the energy gate through a trial-and
      error procedure). At both 80 and 90 ^ C, the coagulation zones generated using
      Area II were significantly larger than that generated using Area I (p = 0.0028
      and 0.0003, respectively) and Area III (P = 0.0010 and < 0.0001, respectively). A
      similar finding regarding the control area and set-point temperature was
      confirmed by the in-vitro experiment. When compared with Point a (p < 0.0001) and
      Point c (p < 0.0001), the largest coagulation zone (1066.7 +/- 36.1 mm2) was
      achieved by controlling the temperature of the tissue area surrounding the middle
      part of the active tip (i.e. Point b) at 90 ^ C. CONCLUSION: The judicious
      selection of the control area within the biological tissue for temperature
      monitoring and the set-point temperature for feedback control is critical in
      increasing the size of the coagulation zone in the treatment of RFA.

PMID- 27868460
TI  - The neurogenetics of Drosophila: the Ganetzky legacy.

PMID- 27868462
TI  - Lower-pole intracapsular tonsillectomy in obstructive sleep apnea patients.
AB  - CONCLUSION: Lower-pole intracapsular tonsillectomy (LPIT) is a valuable surgical
      technique capable of decreasing post-operative bleeding in obstructive sleep
      apnea (OSA) patients. OBJECTIVE: This study performed LPIT to simultaneously
      reduce post-operative bleeding of lower pole and prevent recurrent tonsillitis of
      upper pole and compared its effects to extracapsular tonsillectomy (ET). METHODS:
      ET was performed in the extracapsular plane, with complete monopolar dissection.
      In LPIT, the upper pole of palatine tonsil was removed by electrocautery with the
      extracapsular plane, followed by removal of the lower-pole by plasma ablation
      with the intracapsular plane. Post-operative bleeding incidence, bleeding site,
      and degree of pain were compared between the two groups. RESULTS: Three hundred
      and forty-seven patients diagnosed of OSA with polysomnography were enrolled. ET
      was performed in 152 patients and LPIT in 195 patients. There were no significant
      differences in post-operative pain between the two groups. The LPIT group showed
      significantly lower total bleeding incidence than the ET group (4.1% vs 9.2%; p =
      .05). In particular, lower-pole bleeding incidence was lower in the LPIT group
      than the ET group (1.0% vs 5.3%; p = .02).

PMID- 27868464
TI  - Imatinib resistance in chronic myeloid leukemia due to a rare mutation.

PMID- 27868463
TI  - Postural changes in different stages of schizophrenia is associated with
      inflammation and pain: a cross-sectional observational study.
AB  - OBJECTIVES: To assess the relationship between posture and inflammatory response
      markers (C-reactive protein [CRP] and von Willebrand factor [vWF]) in
      schizophrenics. METHODS: Forty patients with stable schizophrenia were divided
      into early-stage (<10 years since first episode, n = 15) and late-stage (>=10
      years since first episode, n = 25) groups. Both groups were compared to controls
      (n = 26). All participants underwent postural assessment by biophotogrammetry.
      Cases alone underwent blood collection. The significance level was set at 5%, and
      analyses were carried out in SPSS 18.0. RESULTS: In the early-stage group, 15
      postural angles were significantly different from their reference ranges, whereas
      in the late-stage group, only seven angles were significantly different. In
      comparison with the control group, only six angles were significantly different.
      There was no difference in inflammation markers between the early- and late-stage
      groups. However, CRP levels were higher in cases with greater disease severity,
      and vWF was associated with forward head posture. Pain correlated with five
      postural angles, and late-stage patients reported more pain than early-stage
      cases. CONCLUSIONS: CRP was associated with disease severity, while vWF and pain
      were associated with forward head posture, hyperlordosis and scoliosis,
      suggesting an association between vascular inflammation and pain, with an
      influence on posture.

PMID- 27868465
TI  - Comparison of elastosonography and digital examination of cervix for consistency
      to predict successful vaginal delivery after induction of labor with oxytocin.
AB  - OBJECTIVE: To compare elastosonography and digital examination of cervix for
      consistency in the prediction of successful vaginal delivery. METHODS: A total of
      64 pregnant women with the indication of induction of labor (IOL) were enrolled
      to the study. The uterine cervix is evaluated before and after the IOL with
      elastosonography and digital examination for consistency and sonography for
      length. Methods were compared in regard to the prediction of successful vaginal
      delivery. RESULTS: The median of gestational age was 41.00 (IQR = 2.32). Out of
      64 participants, 40 (62.5%) had vaginal delivery and 24 (37.5%) had cesarean
      delivery. The preinduction and postinduction elastosonographic indices were
      insignificant in delivery groups. The preinduction and postinduction evaluations
      of cervical consistency with digital examination were significant within vaginal
      delivery group (p = 0.046), whereas it was insignificant within cesarean delivery
      group and between the delivery groups. The preinduction and postinduction Bishop
      scores were significant within vaginal delivery group (p = 0.005), whereas it was
      insignificant within cesarean delivery group and between the delivery groups.
      Postinduction Bishop score was significant between the delivery groups.
      CONCLUSION: Evaluation of cervix for consistency with either elastosonography or
      digital examination was found to be insignificant in prediction of successful
      vaginal delivery after IOL with oxytocin.

PMID- 27868466
TI  - Double-blind, placebo-controlled, 1:1 randomized Phase III clinical trial of
      Immunoxel honey lozenges as an adjunct immunotherapy in 269 patients with
      pulmonary tuberculosis.
AB  - AIM: Safer and shorter antituberculosis treatment (ATT) regimens represent the
      unmet medical need. PATIENTS & METHODS: The patients were randomly assigned into
      two arms: the first (n = 137) received once-daily sublingual honey lozenge
      formulated with botanical immunomodulator Immunoxel and the second (n = 132)
      received placebo lozenges along with conventional ATT. Immunoxel and placebo arms
      were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus
      20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR
      TB); and 22 versus 20 TB-HIV. The primary end point was sputum smear conversion.
      RESULTS: After 1 month 87 out 132 (65.9%) of Immunoxel recipients became sputum
      smear negative, whereas 32 out of 127 (25.2%) in placebo group had converted (p <
      0.0001). Sputum clearance produced by Immunoxel was equally effective across all
      forms of TB. In the immunotherapy arm the average weight gain was 2 kg, but
      placebo recipients gained only 0.6 kg. Immunoxel reduced TB-associated
      inflammation as evidenced by defervescence and normalization of elevated
      leukocyte counts and erythrocyte sedimentation rate. No adverse effects were seen
      at any time. The liver function tests indicate that ATT-caused hepatotoxicity was
      counteracted by Immunoxel. These results are in agreement with prior 20 trials of
      Immunoxel conducted over the past 17 years. CONCLUSION: Immunoxel is affordable,
      safe, effective, fast-acting, commercially available immunotherapeutic
      intervention to supplement conventional TB chemotherapy. Clinicaltrials.gov ID:
      NCT01061593.

PMID- 27868468
TI  - A mucocele of the appendix seen as an adnexal mass on ultrasound scan.

PMID- 27868469
TI  - Critical review on biofilm methods.
AB  - Biofilms are widespread in nature and constitute an important strategy
      implemented by microorganisms to survive in sometimes harsh environmental
      conditions. They can be beneficial or have a negative impact particularly when
      formed in industrial settings or on medical devices. As such, research into the
      formation and elimination of biofilms is important for many disciplines. Several
      new methodologies have been recently developed for, or adapted to, biofilm
      studies that have contributed to deeper knowledge on biofilm physiology,
      structure and composition. In this review, traditional and cutting-edge methods
      to study biofilm biomass, viability, structure, composition and physiology are
      addressed. Moreover, as there is a lack of consensus among the diversity of
      techniques used to grow and study biofilms. This review intends to remedy this,
      by giving a critical perspective, highlighting the advantages and limitations of
      several methods. Accordingly, this review aims at helping scientists in finding
      the most appropriate and up-to-date methods to study their biofilms.

PMID- 27868470
TI  - Perinatal outcomes and cost-effectivity of the assisted reproduction pregnancies
      with advanced age: A retrospective analysis.
AB  - We demonstrated the IVF-ICSI results, perinatal outcomes and cost-effectivity of
      the patients with advanced age at a tertiary centre. A total of 456 patients
      categorised into two groups according to age: group 1 (n = 158) (>=39years) and
      group 2 (n = 298) (<39years) were analysed retrospectively. In addition, subgroup
      analysis was performed according to the 40 years cut-off. Clinical pregnancy rate
      was significantly different between the groups (p< .001). Preterm delivery (< 37
      gestational week) and low birth weight (< 2500 g) were significantly higher in
      advanced aged women than youngsters (p< .001). Mean expense per cycle for
      hormonal stimulation of IVF-ICSI was 1058.9 and 723.5 USD in groups 1 and 2,
      respectively (p< .001). Mean expense per pregnancy was 9294.7 and 1874.8 USD in
      groups 1 and 2, respectively (p< .001). Our study showed that perinatal outcomes
      and cost-effectivity might be adversely affected with increasing age.

PMID- 27868467
TI  - K+ channel reorganization and homeostatic plasticity during postembryonic
      development: biophysical and genetic analyses in acutely dissociated Drosophila
      central neurons.
AB  - Intrinsic electric activities of neurons play important roles in establishing and
      refining neural circuits during development. However, how the underlying ionic
      currents undergo postembryonic reorganizations remains largely unknown. Using
      acutely dissociated neurons from larval, pupal, and adult Drosophila brains, we
      show drastic re-assemblies and compensatory regulations of voltage-gated (IKv)
      and Ca2+-activated (IK(Ca)) K+ currents during postembryonic development. Larval
      and adult neurons displayed prominent fast-inactivating IKv, mediated by the
      Shaker (Sh) channel to a large extent, while in the same neurons IK(Ca) was far
      smaller in amplitude. In contrast, pupal neurons were characterized by large
      sustained IKv and prominent IK(Ca), encoded predominantly by the slowpoke (slo)
      gene. Surprisingly, deletion of Sh in the ShM null mutant removed inactivating,
      transient IKv from large portions of neurons at all stages. Interestingly,
      elimination of Sh currents was accompanied by upregulation of non-Sh transient
      IKv. In comparison, the slo1 mutation abolished the vast majority of IK(Ca),
      particularly at the pupal stage. Strikingly, the deficiency of IK(Ca) in slo
      pupae was compensated by the transient component of IKv mediated by Sh channels.
      Thus, IK(Ca) appears to play critical roles in pupal development and its absence
      induces functional compensations from a specific transient IKv current. While
      mutants lacking either Sh or slo currents survived normally, Sh;;slo double
      mutants deficient in both failed to survive through pupal metamorphosis.
      Together, our data highlight significant reorganizations and homeostatic
      compensations of K+ currents during postembryonic development and uncover
      previously unrecognized roles for Sh and slo in this plastic process.

PMID- 27868471
TI  - Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30
      undetectable by visual assessment of conventional immunohistochemistry.
AB  - This phase 2 study evaluated brentuximab vedotin monotherapy in CD30-expressing
      DLBCL; after several patients with little to no CD30 achieved a complete
      remission (CR), the study evaluated treatment of DLBCL with undetectable CD30
      (CD30u) by local visual immunohistochemistry (vIHC). Sixteen of 52 CD30u DLBCL
      patients (31%) had an objective response (6 CRs [12%]). Median progression-free
      survival (PFS) was 1.4 months (range, 0.4-15.6) and median overall survival (OS)
      was 7.5 months (range, 0.7-18.6+). Subsequent CD30 expression quantitated by
      computer-assisted digital image analysis (cIHC) showed that 11 of 16 CD30u DLBCL
      responders had >=1% CD30. Correlative analyses of CD30u and CD30-expressing DLBCL
      combined demonstrated that >=1% CD30 expression by cIHC resulted in a trend
      toward a higher response rate and significantly longer median PFS and OS. A
      minimum CD30 expression threshold appears to be required for antitumor activity
      in DLBCL; however, other factors also likely contribute to activity.
      (NCT01421667).

PMID- 27868473
TI  - Corrigendum.

PMID- 27868474
TI  - Persistent trophoblastic disease at caesarean scar and its successful treatment
      with multiple dose systemic methotrexate after suction curettage.

PMID- 27868472
TI  - Topical and systemic antifungals in dermatology practice.
AB  - INTRODUCTION: Dermatophytosis is generally defined as an infection of the hair,
      nails, or glabrous skin. These infections are caused by the keratinophilic fungi
      Trichophyton spp., Microsporum spp., and Epidermophyton, which have been
      recovered from both symptomatic and asymptomatic individuals. Although
      dermatophytosis is generally not a life-threatening condition, these types of
      infections are among the most common infections worldwide, and their incidence
      has continued to increase consistently in recent years. Area covered: This
      article provides an overview of the general characteristics of dermatophytes,
      including their taxonomy and epidemiology, as well as the different clinical
      forms and laboratory diagnostics of dermatophytosis. We further classify the
      topical and systemic antifungal compounds currently used to treat dermatophyte
      infections. Expert commentary: Antifungal therapy is a central component of
      patient management for dermatophytosis, and depending on the strategy chosen,
      topical and/or systemic drugs can be used. However, for effective treatment, it
      is important to correctly determine the causal agents at the species level, which
      will enable administration of suitable therapeutics and initiation of appropriate
      management strategies.

PMID- 27868475
TI  - Collision count in rugby union: A comparison of micro-technology and video
      analysis methods.
AB  - The aim of our study was to determine if there is a role for manipulation of g
      force thresholds acquired via micro-technology for accurately detecting
      collisions in rugby union. In total, 36 players were recruited from an elite
      Guinness Pro12 rugby union team. Player movement profiles and collisions were
      acquired via individual global positioning system (GPS) micro-technology units.
      Players were assigned to a sub-category of positions in order to determine
      positional collision demands. The coding of collisions by micro-technology at g
      force thresholds between 2 and 5.5 g (0.5 g increments) was compared with
      collision coding by an expert video analyst using Bland-Altman assessments. The
      most appropriate g force threshold (smallest mean difference compared with video
      analyst coding) was lower for all forwards positions (2.5 g) than for all backs
      positions (3.5 g). The Bland-Altman 95% limits of agreement indicated that there
      may be a substantial over- or underestimation of collisions coded via GPS micro
      technology when using expert video analyst coding as the reference comparator.
      The manipulation of the g force thresholds applied to data acquired by GPS micro
      technology units based on incremental thresholds of 0.5 g does not provide a
      reliable tool for the accurate coding of collisions in rugby union. Future
      research should aim to investigate smaller g force threshold increments and
      determine the events that cause coding of false positives.

PMID- 27868477
TI  - Association between olfaction and higher cortical functions in Alzheimer's
      disease, mild cognitive impairment, and healthy older adults.
AB  - INTRODUCTION: Neural regions important for smell are proximal and closely
      connected to cortical areas that have been strongly implicated in higher order
      functions of value-based decision making and emotional memory. The integrity of
      these neural regions are affected in aging and neurodegenerative conditions. Two
      specific predictions follow from these neuroanatomical arrangements-namely, that
      olfaction would be associated with value-based decision making and with emotional
      memory. METHOD: To test these predictions, we measured these different capacities
      in participants with presumed varying degrees of integrity of the relevant brain
      structures: specifically, 13 patients with Alzheimer's disease, 8 patients with
      mild cognitive impairment, and 20 healthy older adults. The participants
      completed detailed tests of olfaction, value-based decision making, emotional
      memory, and general cognitive ability. RESULTS: Olfactory functioning was
      significantly associated with emotional and nonemotional memory. The association
      was especially strong and consistent for memory recall with olfaction, explaining
      as much as 10% additional variance over and above general cognition. Olfactory
      functioning was not strongly or consistently associated with decision making over
      and above general cognition. CONCLUSION: Olfaction is a strong predictor of
      memory recall. These findings may contribute to a better understanding of
      olfaction and specific cognitive domains known to be affected by aging and
      implicated in neurodegenerative disease.

PMID- 27868476
TI  - Latent structure of cognitive performance in the adult children study.
AB  - OBJECTIVE: The Adult Children Study (ACS) at the Knight Alzheimer's Disease
      Research Center is a longitudinal investigation designed to identify and validate
      potential biomarkers of preclinical Alzheimer's disease (AD) in cognitively
      normal individuals with and without a family history of AD. The purpose of the
      current study was to validate the proposed latent structure of the ACS
      psychometric battery. METHOD: Confirmatory factor analyses of baseline data in a
      sample of 229 (75 men) cognitively normal middle-aged to older adult individuals
      assessed a hypothesized 4-factor model of cognitive performance. Measurement
      invariance was investigated as a function of family history of AD and
      apolipoprotein E (APOE) status. RESULTS: This study confirmed a priori hypotheses
      of 4 latent cognitive domains in a unique longitudinal sample of cognitively
      normal adults. In addition, there was evidence of a similar factor structure for
      family history and APOE status groups. CONCLUSION: These robust indicators of a
      broad range of cognitive domains will be used in future investigations to track
      the influence of family history of AD on cognitive performance over time. In
      addition, associations with fluid, structural, and molecular biomarkers of
      preclinical AD will be further examined, both cross-sectionally and
      longitudinally in this sample.

PMID- 27868478
TI  - Genetic Diversity and Gene Flow of Four South African Venturia inaequalis (Apple
      Scab) Populations.
AB  - Venturia inaequalis isolates were collected during the 2012/13 and 2013/14
      seasons from the four principal apple growing regions of South Africa, Elgin (n =
      114), Koue Bokkeveld (n = 126), Lower Langkloof (n = 92), and Upper Langkloof (n
      = 103). Sequence analysis of the ribosomal internal transcribed spacer (ITS) gene
      regions and genotyping with six (2012/13) and seven (2013/14) microsatellite
      (SSR) markers was conducted. A subset of 12 isolates from the individual ITS
      haplotype groups were sequenced for the translation elongation factor-1 alpha
      (TEF1) and the large subunit of the RNA polymerases II (RPB1) gene regions. Four
      haplotypes were found for ITS, whereas all isolates were identical for the TEF1
      and RPB1 gene regions. The SSR markers revealed considerable variation with an
      average gene diversity (H) of 0.675. Multivariate analysis (discriminant analysis
      of principal components [DAPC]) revealed that the two Langkloof populations
      clustered together with the Koue Bokkeveld population. The population from the
      warmer winter region, Elgin, clustered separately from the rest of the
      populations (PhiPT = 0.076 to 0.116; P <= 0.05). Estimates of gene flow showed
      the highest migration rate from the Koue Bokkeveld, toward the Lower Langkloof (M
      = 151.1), and the least migration to and from the Elgin region (average M =
      42.75). Occasionally, identical genotypes (clones) were detected across seasons
      in the Koue Bokkeveld and Elgin area, which might contribute to overwintering
      conidia. From this study, it is evident that South Africa most likely has V.
      inaequalis subpopulations linked to diverse climatic conditions of the coastal
      Elgin region compared with the mountainous inland regions of the Koue Bokkeveld
      and the Langkloof.

PMID- 27868479
TI  - Mapping Resistance to Alternaria cucumerina in Cucumis melo.
AB  - Infection with Alternaria cucumerina causes Alternaria leaf blight (ALB), a
      disease characterized by lesion formation on leaves, leading to substantial yield
      and quality losses in Cucumis melo (melon). Although fungicides are effective
      against ALB, reduction in the frequency of application would be economically and
      environmentally beneficial. Resistant melon lines have been identified but the
      genetic basis of this resistance has not been determined. A saturated melon
      genetic map was constructed with markers developed through genotyping by
      sequencing of a recombinant inbred line population (F6 to F10; n = 82) derived
      from single-seed descent of a F2 population from a cross between the ALB
      resistant parent MR-1 and the ALB-susceptible parent Ananas Yokneum. The
      population was evaluated for A. cucumerina resistance with an augmented block
      greenhouse study using inoculation with the wounded-leaf method. Multiple
      quantitative trait loci (QTL) mapping identified two QTL that explained 33.9% of
      variation in lesion area. Several candidate genes within range of these QTL were
      identified using the C. melo v3.5 genome. Markers linked to these QTL will be
      used to accelerate efforts to breed melon cultivars resistant to ALB.

PMID- 27868480
TI  - Revealing the decision-making of dribbling in the sport of futsal.
AB  - This study aimed to investigate why futsal players decide to dribble. For this
      purpose, we analysed 396 trials comprising the dribbles (n = 132), passes (n =
      131) or shots (n = 133), performed by 70 male futsal players. Passing and
      shooting angles, and interpersonal distance, including their rates of change
      (velocity and variability), were regarded as measures of interpersonal
      coordination tendency and a comparison was made among dribbling, passing and
      shooting situations. In addition, the variables identified as constraints on
      deciding to dribble were analysed in relation to age categories, dribbling
      outcomes and futsal court zone. Results revealed that passing and shooting
      angles, and interpersonal distance showed higher variability in dribbling than in
      passing and shooting situations. The findings allowed us to conclude that
      decision-making on dribbling was influenced by the variabilities of passing
      angles as well as shooting and interpersonal distance, and that success in
      dribbling was affected by the variability of interpersonal distance. Such
      variabilities were interpreted concerning their meaning of risk and/or
      uncertainty in the execution of motor skills.

PMID- 27868481
TI  - Inconsistent-handed advantage in episodic memory extends to paragraph-level
      materials.
AB  - Past research using handedness as a proxy for functional access to the right
      hemisphere demonstrates that individuals who are mixed/inconsistently handed
      outperform strong/consistently handed individuals when performing episodic recall
      tasks. However, research has generally been restricted to stimuli presented in a
      list format. In the present paper, we present two studies in which participants
      were presented with paragraph-level material and then asked to recall material
      from the passages. The first study was based on a classic study looking at
      retroactive interference with prose materials. The second was modelled on a
      classic experiment looking at perspective taking and the content of memory. In
      both studies, the classic effects were replicated and the general finding that
      mixed/inconsistent-handers outperform strong/consistent-handers was replicated.
      This suggests that considering degree of handedness may be an empirically useful
      means of reducing error variance in paradigms looking at memory for prose level
      material.

PMID- 27868580
TI  - Attention lapses in children with spina bifida and hydrocephalus and children
      with attention-deficit/hyperactivity disorder.
AB  - Attentional lapses are usually defined as temporary and often brief shifts of
      attention away from some primary task to unrelated internal information
      processing. This study addressed the incidence of attention lapses and
      differences in attentional functioning in 30 children with attention
      deficit/hyperactivity disorder (ADHD), 26 healthy children, and 29 children with
      spina bifida myelomeningocele and hydrocephalus (SBH). Assessments were conducted
      using computerized tonic and phasic attention tests, the Symbol Digit Modalities
      Test (SDMT), and the Trail Making Test Form B (TMT-B). The group with SBH
      differed from normal controls on cognitive measures of attention and executive
      functions. The ADHD group obtained lower scores than the SBH group and healthy
      children. ANOVA results showed that there was an effect of shunt revisions and
      shunt-related infections on neuropsychological performance. Lapses of attention
      together with reaction time may thus represent important factors for the
      understanding of cognitive deficits in SBH.

PMID- 27868581
TI  - 2016 Updated American Society of Clinical Oncology/Oncology Nursing Society
      Chemotherapy Administration Safety Standards, Including Standards for Pediatric
      Oncology.
AB  - Purpose To update the ASCO/Oncology Nursing Society (ONS) Chemotherapy
      Administration Safety Standards and to highlight standards for pediatric
      oncology. Methods The ASCO/ONS Chemotherapy Administration Safety Standards were
      first published in 2009 and updated in 2011 to include inpatient settings. A
      subsequent 2013 revision expanded the standards to include the safe
      administration and management of oral chemotherapy. A joint ASCO/ONS workshop
      with stakeholder participation, including that of the Association of Pediatric
      Hematology Oncology Nurses and American Society of Pediatric Hematology/Oncology,
      was held on May 12, 2015, to review the 2013 standards. An extensive literature
      search was subsequently conducted, and public comments on the revised draft
      standards were solicited. Results The updated 2016 standards presented here
      include clarification and expansion of existing standards to include pediatric
      oncology and to introduce new standards: most notably, two-person verification of
      chemotherapy preparation processes, administration of vinca alkaloids via
      minibags in facilities in which intrathecal medications are administered, and
      labeling of medications dispensed from the health care setting to be taken by the
      patient at home. The standards were reordered and renumbered to align with the
      sequential processes of chemotherapy prescription, preparation, and
      administration. Several standards were separated into their respective components
      for clarity and to facilitate measurement of adherence to a standard. Conclusion
      As oncology practice has changed, so have chemotherapy administration safety
      standards. Advances in technology, cancer treatment, and education and training
      have prompted the need for periodic review and revision of the standards.
      Additional information is available at http://www.asco.org/chemo-standards .

PMID- 27868689
TI  - Effect of long-term application of pretilachlor on its persistence and residues
      in paddy crop.
AB  - The effect of long-term application of pretilachlor to paddy in rice-wheat
      cropping system was investigated from 1997 to 2015. Additionally, in 2013, field
      experiment was also conducted where pretilachlor was applied to paddy field
      having no background of its application. The residues of pretilachlor were
      quantified using high-performance liquid chromatography (HPLC). The average
      recoveries of pretilachlor from paddy soil, paddy grain and straw samples ranged
      from 80.7% to 93.8% using HPLC with standard deviation less than 10%. The
      dissipation rate of pretilachlor in paddy soil followed first-order kinetics and
      half-life ranged from 9.58 to 21.19 days. In 2015, HPLC was compared with gas
      chromatography-tandem mass spectrometry (GC-MS/MS) for quantification of
      residues. Average recoveries of pretilachlor using GC-MS/MS from paddy soil,
      paddy grain and straw samples ranged from 81.4% to 98.3% with standard deviation
      less than 10%. Both HPLC and GC-MS/MS offered high reproducibility; however GC
      MS/MS was more sensitive and the limit of detection was 3.0 and 1.0 ng g-1 for
      HPLC and GC-MS/MS, respectively. At harvest, the residues of pretilachlor in the
      paddy soil and crop were below the maximum residue limit and no dangerous
      accumulation was observed after its prolonged application.

PMID- 27868947
TI  - Diet and nutrients in the modulation of infant sleep: A review of the literature.
AB  - OBJECTIVES: The establishment of organized sleep patterns is an important
      developmental process during infancy. Little is known about the role of nutrition
      in sleep maturation. This review focuses on exploring the link between infant
      sleep and nutrition with the aim to provide an overview of existing literature on
      the impact of diet and specific nutrients on sleep modulation in infants.
      METHODS: An exploratory literature search was performed on the topic in Medline,
      Scopus and Cochrane Library databases, with a focus on publications in English.
      RESULTS: Both the type of nutrients consumed and the timing at which they were
      consumed, relative to sleeping time, have been reported to influence infant
      sleep. Some nutrients have been shown to naturally fluctuate in maternal breast
      milk with circadian rhythm, and nutrients such as tryptophan, nucleotides,
      essential fatty acids and Omega-3 long-chain fatty acids have been suggested to
      impact infant sleep. DISCUSSION: In summary, little is known about the
      nutritional impact on infant sleep and sleep maturation, particularly with regard
      to specific nutrients. While nutrients like tryptophan and nucleotides seem to
      impact sleep at the level of brain activity, some fatty acids may affect sleep as
      a result of their role in supporting the maturity of the central nervous system.
      In our view, the existing literature indicates that the link between nutrition
      and infant sleep may be a promising concept to support this crucial phase of
      early development.

PMID- 27868798
TI  - Neurochemical and behavioral effects of Nigella sativa and Olea europaea oil in
      rats.
AB  - OBJECTIVES: In the last few decades, therapeutic uses of medicinal compounds
      present in food as a normal constituent has risen substantially, largely because
      of their fewer side effects and adequate efficacy. This study is designed to
      investigate a role of brain serotonin (5-HT) and dopamine (DA) in the potential
      nootropic, anxiolytic, and other beneficial effects of Nigella sativa (NS) and
      Olea europaea (OE) oil in rat models. METHODS: Animals were treated with NS and
      OE oil orally at doses of 0.1 ml/kg and 0.25 ml/kg for 5 weeks. Food intake and
      body weight change, anxiety-like effects in elevated plus maze and activity in a
      novel and familiar environment were monitored weekly. Effects on learning and
      memory after 5 weeks treatment were monitored using Morris water maze test.
      Neurochemical analysis was carried using HPLC-ECD method. RESULTS: NS and OE oil
      administration enhanced learning and memory in Morris water maze test and the
      effects were greater in NS than OE oil-treated animals. Low dose of OE oil
      increased exploration in an open field, higher dose of OE oil and both doses of
      NS oil produced no consistent effect on open field exploration. Effects of both
      oils on anxiety-like behavior, food and water intake, and activity in activity
      box were either not consistent or did not occur. The treatment increased
      homovanillic acid (HVA). 5-HT levels increased in high dose of NS oil and low
      dose of OE oil-treated groups. Low dose NS oil decreased 5-HT. DISCUSSION: The
      present study suggests that active components in NS and OE oil may prove useful
      in treating impaired cognition. OE oil may produce psychostimulant-like effect.
      Modulation of DA and serotonin neurotransmission seems important in the
      pharmacological effect of these oils.

PMID- 27869039
TI  - The role of rs1984112_G at CD36 gene in increasing reticulocyte level among
      sickle cell disease patients.
AB  - AIMS AND BACKGROUND: Mediators of adhesion become a potential new target for
      pharmacological therapy to struggle the complications of sickle cell disease
      (SCD). Several mechanisms for increased adherence have been postulated and the
      well-studied are CD36 and VLA4 which encoded by ITGA4. Herein, we sought to
      determine whether one polymorphism of CD36 namely: rs1984112 and three exons of
      ITGA4 (4, 5, and 6) are implicated in hemolytic status and clinical events among
      SCD Tunisian patients. MATERIAL AND METHODS: This study enrolled 99 unrelated
      Tunisian subjects (63SS and 36Sbeta). All SCD patients are children (less than 16
      years old). The rs1984112 and the ITGA4's exons 4, 5, and 6 were analyzed for all
      subjects by PCR/sequencing. The association of each genotype found with both
      clinical complications and hemolytic status was performed using t-test. Clinical
      events studied included vaso-occlusive crisis (VOC), osteonecrosis, stroke,
      frequent infection, priapism, and acute syndrome. RESULTS: The results show that
      rs1984112_G allele at CD36 gene revealed to be associated with higher levels of
      reticulocyte count (p < 0.01). The statistical result show a near significance of
      homozygous mutant GG genotype with VOC (p = 0.051). No association between
      rs1984112_G allele and the clinical severity of SCD were found. Mutational
      screening of exon 4, 5, and 6 of ITGA4 gene revealed absence of mutated variant.
      CONCLUSION: Our results are similar to those found in Portuguese population which
      reported the role of rs1984112_G in increasing reticulocyte level among SCD
      patients. Consequently, the rs1984112_G of CD36 could be considered as a reliable
      biomarker for predicting patients at high risk for vascular occlusions and thus,
      allows earlier and more effective therapeutic management.

PMID- 27869040
TI  - Natural or Artificial? Multi-Analytical Study of a Scagliola from Estoi Palace
      Simulating Imperial Red Porphyry.
AB  - In this paper the characterization of a gypsum plaster sample from the end of the
      19th century simulating imperial red porphyry using a multi-analytical approach
      is presented and discussed. The results of X-ray diffraction (XRD),
      thermogravimetric and differential thermal analysis (TGA-DTA), physical and
      mechanical properties are summarized. In order to have further insight into the
      microstructure, polarized light microscopy (PLM), scanning electron microscopy
      coupled with energy dispersive X-ray spectrometer (SEM-EDS), and micro Raman
      spectroscopy analyzes were also made. They helped to clarify the main issues
      raised by the other complementary analytical techniques and allowed the
      establishment of interrelations between the different properties, providing
      important information about the materials, the skills, and the technological
      development involved in the art of imitating noble stones with gypsum pastes.
      This study also contributes to our knowledge concerning the preservation of these
      types of elements that are important in the context of European decorative arts
      and rarely reported in the literature.

PMID- 27869041
TI  - Wolff-Parkinson-White syndrome: a single exercise stress test might be
      misleading.
AB  - Risk stratification of patients with Wolff-Parkinson-White syndrome for sudden
      death is a complex process, particularly in understanding the utility of the
      repeat exercise stress test. We report a case of an 18-year-old patient who was
      found to have a high-risk pathway by both invasive and exercise stress testing
      after an initial exercise stress test showing beat-to-beat loss of pre
      excitation.

PMID- 27869042
TI  - Invited review: efficient computation strategies in genomic selection.
AB  - The purpose of this study is review and evaluation of computing methods used in
      genomic selection for animal breeding. Commonly used models include SNP BLUP with
      extensions (BayesA, etc), genomic BLUP (GBLUP) and single-step GBLUP (ssGBLUP).
      These models are applied for genomewide association studies (GWAS), genomic
      prediction and parameter estimation. Solving methods include finite Cholesky
      decomposition possibly with a sparse implementation, and iterative Gauss-Seidel
      (GS) or preconditioned conjugate gradient (PCG), the last two methods possibly
      with iteration on data. Details are provided that can drastically decrease some
      computations. For SNP BLUP especially with sampling and large number of SNP, the
      only choice is GS with iteration on data and adjustment of residuals. If only
      solutions are required, PCG by iteration on data is a clear choice. A genomic
      relationship matrix (GRM) has limited dimensionality due to small effective
      population size, resulting in infinite number of generalized inverses of GRM for
      large genotyped populations. A specific inverse called APY requires only a small
      fraction of GRM, is sparse and can be computed and stored at a low cost for
      millions of animals. With APY inverse and PCG iteration, GBLUP and ssGBLUP can be
      applied to any population. Both tools can be applied to GWAS. When the system of
      equations is sparse but contains dense blocks, a recently developed package for
      sparse Cholesky decomposition and sparse inversion called YAMS has greatly
      improved performance over packages where such blocks were treated as sparse. With
      YAMS, GREML and possibly single-step GREML can be applied to populations with >50
      000 genotyped animals. From a computational perspective, genomic selection is
      becoming a mature methodology.

PMID- 27869043
TI  - Nano-Localized Thermal Analysis and Mapping of Surface and Sub-Surface Thermal
      Properties Using Scanning Thermal Microscopy (SThM).
AB  - Determining and acting on thermo-physical properties at the nanoscale is
      essential for understanding/managing heat distribution in micro/nanostructured
      materials and miniaturized devices. Adequate thermal nano-characterization
      techniques are required to address thermal issues compromising device
      performance. Scanning thermal microscopy (SThM) is a probing and acting technique
      based on atomic force microscopy using a nano-probe designed to act as a
      thermometer and resistive heater, achieving high spatial resolution. Enabling
      direct observation and mapping of thermal properties such as thermal
      conductivity, SThM is becoming a powerful tool with a critical role in several
      fields, from material science to device thermal management. We present an
      overview of the different thermal probes, followed by the contribution of SThM in
      three currently significant research topics. First, in thermal conductivity
      contrast studies of graphene monolayers deposited on different substrates, SThM
      proves itself a reliable technique to clarify the intriguing thermal properties
      of graphene, which is considered an important contributor to improve the
      performance of downscaled devices and materials. Second, SThM's ability to
      perform sub-surface imaging is highlighted by thermal conductivity contrast
      analysis of polymeric composites. Finally, an approach to induce and study local
      structural transitions in ferromagnetic shape memory alloy Ni-Mn-Ga thin films
      using localized nano-thermal analysis is presented.

PMID- 27869044
TI  - Relationship between the home environment and fruit and vegetable consumption in
      children aged 6-12 years: a systematic review.
AB  - OBJECTIVE: As numerous factors in the home environment have been related to
      children's fruit and vegetable (F&V) consumption as a component of a healthy
      diet, the purpose of the present systematic review was to examine these factors
      specifically for children aged 6-12 years. DESIGN: Relevant observational studies
      published in English between January 2007 and December 2015 were obtained through
      electronic database searches. Studies were included if the researchers reported
      on a potentially modifiable measure of the home physical, political and
      sociocultural environment related to child F&V consumption. RESULTS: Of the
      thirty-three articles reviewed, overall methodological quality was poor with
      twenty studies rated as weak, mainly due to cross-sectional design (majority of
      studies), selection bias, convenience sampling and voluntary participation. Half
      of the studies had strong-moderate ratings for using valid and/or reliable tools
      while for the other half, psychometric properties were either not reported or
      weak. The most consistent evidence for children's combined F&V consumption was
      found for availability and accessibility of F&V, parental role modelling of F&V
      and maternal intake of F&V. CONCLUSIONS: A vast array of home environment
      components and their influence on children's consumption of fruits and/or
      vegetables have been studied in recent years. Specific components of the home
      environment may have more influence than others, but more compelling evidence is
      needed to draw strong conclusions. Recommendations are made for future studies to
      be based upon conceptual/theoretical models to provide consistency in defining
      the home environment and investigation of potential moderators, such as personal
      or contextual factors.

PMID- 27869045
TI  - Commentary on Cummings et al.

PMID- 27869047
TI  - Children's exposure to violent political conflict stimulates aggression at peers
      by increasing emotional distress, aggressive script rehearsal, and normative
      beliefs favoring aggression.
AB  - We examine the hypothesis that children's exposure to ethnic-political conflict
      and violence over the course of a year stimulates their increased aggression
      toward their own in-group peers in subsequent years. In addition, we examine what
      social cognitive and emotional processes mediate these effects and how these
      effects are moderated by gender, age, and ethnic group. To accomplish these aims,
      we collected three waves of data from 901 Israeli and 600 Palestinian youths
      (three age cohorts: 8, 11, and 14 years old) and their parents at 1-year
      intervals. Exposure to ethnic-political violence was correlated with aggression
      at in-group peers among all age cohorts. Using a cross-lagged structural equation
      model from Year 1 to Year 3, we found that the relation between exposure and
      aggression is more plausibly due to exposure to ethnic-political violence
      stimulating later aggression at peers than vice versa, and this effect was not
      moderated significantly by gender, age cohort, or ethnic group. Using three-wave
      structural equation models, we then showed that this effect was significantly
      mediated by changes in normative beliefs about aggression, aggressive script
      rehearsal, and emotional distress produced by the exposure. Again the best
      fitting model did not allow for moderation by gender, age cohort, or ethnic
      group. The findings are consistent with recent theorizing that exposure to
      violence leads to changes both in emotional processes promoting aggression and in
      the acquisition through observational learning of social cognitions promoting
      aggression.

PMID- 27869046
TI  - Latino mothers' beliefs about child weight and family health.
AB  - OBJECTIVE: There is a need to address cultural beliefs and parenting practices
      regarding childhood obesity to design effective weight-control programmes for
      overweight/obese US Latino children. The purpose of the current study was to
      explore cultural beliefs about children's weight, understand parent perceptions
      on feeding their children, and explore barriers that interfere with a healthy
      lifestyle. DESIGN: Four focus groups were conducted in Spanish with forty-one
      Latino mothers of elementary school-age children from San Diego County,
      California between April and May 2011. Cultural viewpoints about overweight
      status among children and barriers to leading a healthy lifestyle were explored.
      Focus group discussions were analysed based on a priori and emergent themes.
      RESULTS: Three themes were identified: (i) mothers' cultural beliefs about health
      that are barriers to family health; (ii) mothers as primary caretakers of their
      family's health; and (iii) attitudes about targeting children's weight. Mothers
      acknowledged the idea that 'chubby is better' is a misperception, yet having a
      'chubby' child was preferred and even accepted. Mothers described fatalistic
      beliefs that contradicted existing knowledge of chronic disease and daily demands
      of Western culture as barriers to practising healthy behaviours in the home as
      the family caretaker. CONCLUSIONS: These findings may be used to inform more
      culturally appropriate research to address US Latino health. Increasing awareness
      of cultural beliefs and daily circumstance could help to address obesity more
      directly and thereby overcome some of the potential underlying barriers that
      might exist when involving the Latino immigrant families in obesity treatment and
      prevention.

PMID- 27869050
TI  - WISDOM AND THE PATH-DEPENDENT POLITICS OF BIOMEDICAL RESEARCH.

PMID- 27869048
TI  - Efficacy, safety, and tolerability of vortioxetine for the treatment of major
      depressive disorder in patients aged 55 years or older.
AB  - OBJECTIVE: These post hoc analyses evaluate the efficacy, safety, and
      tolerability of vortioxetine versus placebo in patients aged >=55 years with
      major depressive disorder (MDD). METHODS: Study-level efficacy data from 12 short
      term, fixed-dose, randomized, placebo-controlled trials of vortioxetine 5-20
      mg/day were assessed using a random-effects meta-analysis. Adverse events (AEs),
      vital signs, ECG values, liver enzymes, and body weight were pooled from the same
      studies. Patients had baseline Montgomery-Asberg Depression Rating Scale (MADRS)
      total scores ranging from 22-30. RESULTS: 1508 patients (mean age=62.4 years;
      range, 55-88 years) were included. Mean differences from placebo in change from
      baseline to study end (6/8 weeks) in MADRS were -2.56 (5 mg, n=324, P=0.035), 
      2.87 (10 mg, n=222, P=0.007), -1.32 (15 mg, n=90, P=NS), and -4.65 (20 mg, n=165,
      P=0.012). Odds ratios for response versus placebo were 1.6 (5 mg, P=NS), 1.8 (10
      mg, P=0.002), 1.2 (15 mg, P=NS), and 2.5 (20 mg, P<0.001), and for remission
      versus placebo were 1.5 (5 mg, P=NS), 1.5 (10 mg, P=NS), 1.4 (15 mg, P=NS), and
      2.7 (20 mg, P=0.001). The proportion of patients with AEs for placebo and
      vortioxetine 5-20 mg was 61.5% and 62.3%, respectively, with no increase at
      increased doses. Vortioxetine demonstrated a placebo-level incidence of serious
      AEs (1.2%). AEs occurring in >=5% of any treatment group were nausea, headache,
      diarrhea, dizziness, dry mouth, constipation, fatigue, vomiting, and anxiety. No
      clinically significant mean changes in vital signs, ECG values, liver enzymes, or
      body weight emerged during treatment. CONCLUSION: Vortioxetine 5-20 mg/day is
      efficacious and well tolerated in MDD patients aged >=55 years, a group that is
      often comorbid with other conditions and treated with other medications.

PMID- 27869049
TI  - Exclusion of overlapping symptoms in DSM-5 mixed features specifier: heuristic
      diagnostic and treatment implications.
AB  - This article focuses on the controversial decision to exclude the overlapping
      symptoms of distractibility, irritability, and psychomotor agitation (DIP) with
      the introduction of the Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition (DSM-5) mixed features specifier. In order to understand the
      placement of mixed states within the current classification system, we first
      review the evolution of mixed states. Then, using Kraepelin's original
      classification of mixed states, we compare and contrast his conceptualization
      with modern day definitions. The DSM-5 workgroup excluded DIP symptoms, arguing
      that they lack the ability to differentiate between manic and depressive states;
      however, accumulating evidence suggests that DIP symptoms may be core features of
      mixed states. We suggest a return to a Kraepelinian approach to classification
      with mood, ideation, and activity as key axes-and reintegration of DIP symptoms
      as features that are expressed across presentations. An inclusive definition of
      mixed states is urgently needed to resolve confusion in clinical practice and to
      redirect future research efforts.

PMID- 27869051
TI  - Money is Brain: Financial Barriers and Consequences for Canadian Stroke Patients.
AB  - BACKGROUND: Stroke patients of lower socioeconomic status have worse outcomes. It
      remains poorly understood whether this is due to illness severity or personal or
      health system barriers. We explored the experiences of stroke patients with
      financial barriers in a qualitative descriptive pilot study, seeking to capture
      perceived challenges that interfere with their poststroke health and recovery.
      METHODS: We interviewed six adults with a history of stroke and financial
      barriers in Alberta, Canada, inquiring about their: (1) experiences after stroke;
      (2) experience of financial barriers; (3) perceived reasons for financial
      barriers; (4) health consequences of financial barriers; and (5) mechanisms for
      coping with financial barriers. Two reviewers analyzed data using inductive
      thematic analysis. RESULTS: The participants developed new or worsened financial
      circumstances as a consequence of stroke-related disability. Poststroke
      impairments and financial barriers took a toll on their mental health. They
      struggled to access several aspects of long-term poststroke care, including
      allied health professional services, medications, and proper nutrition. They
      described opportunity costs and tradeoffs when accessing health services. In
      several cases, they were unaware of health resources available to them and were
      hesitant to disclose their struggles to their physicians and even their families.
      CONCLUSION: Some patients with financial barriers perceive challenges to
      accessing various aspects of poststroke care. They may have inadequate knowledge
      of resources available to them and may not disclose their concerns to their
      health care team. This suggests that providers themselves might consider asking
      stroke patients about financial barriers to optimize their long-term poststroke
      care.

PMID- 27869052
TI  - Altering management decisions with gained anatomical insight from a 3D printed
      model of a complex ventricular septal defect.
AB  - Rapid prototyping is quickly gaining utility in various complex forms of CHD. In
      properly selected cases, these printed models provide detailed anatomical
      understanding that help guide potential surgical and cardiac catheterisation
      interventions. We present a case of a tunnel-like ventricular septal defect
      referred for surgical repair, where the decision to obtain a three-dimensional
      printed model helped in better understanding of the anatomy, leading to delaying,
      and hopefully avoiding altogether, surgical repair.

PMID- 27869053
TI  - Incidence, risk factors, and outcomes of acute kidney injury in adults undergoing
      surgery for congenital heart disease.
AB  - BACKGROUND: Acute kidney injury after cardiac surgery is a frequent and serious
      complication among children with congenital heart disease (CHD) and adults with
      acquired heart disease; however, the significance of kidney injury in adults
      after congenital heart surgery is unknown. The primary objective of this study
      was to determine the incidence of acute kidney injury after surgery for adult
      CHD. Secondary objectives included determination of risk factors and associations
      with clinical outcomes. METHODS: This single-centre, retrospective cohort study
      was performed in a quaternary cardiovascular ICU in a paediatric hospital
      including all consecutive patients ?18 years between 2010 and 2013. RESULTS: Data
      from 118 patients with a median age of 29 years undergoing cardiac surgery were
      analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36%
      of patients developed kidney injury, with 5% being moderate to severe (stage
      2/3). Among higher-complexity surgeries, incidence was 59%. Age ?35 years,
      preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass
      time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and
      perioperative vancomycin use were significant risk factors for kidney injury
      development. In multivariable analysis, age ?35 years and vancomycin use were
      significant predictors. Those with kidney injury were more likely to have
      prolonged duration of mechanical ventilation and cardiovascular ICU stay in the
      univariable regression analysis. CONCLUSIONS: We demonstrated that acute kidney
      injury is a frequent complication in adults after surgery for CHD and is
      associated with poor outcomes. Risk factors for development were identified but
      largely not modifiable. Further investigation within this cohort is necessary to
      better understand the problem of kidney injury.

PMID- 27869054
TI  - Percutaneous closure of an aortopulmonary window using Amplatzer Duct Occluder
      II: Additional Sizes: the first reported case.
AB  - To date, there are no reported cases of the Amplatzer Duct Occluder II:
      Additional Sizes' use in percutaneous closure of an aortopulmonary window. We
      report a case of percutaneous closure of an aortopulmonary window in a 4.5-month
      old, 6 kg child. Owing to the patient's low weight, high risk of damage to the
      pulmonary valve, as well as the possibility of aortic and pulmonary artery
      obstruction, classic implants were deemed unsuitable and a decision was made to
      use the Amplatzer Duct Occluder II: Additional Sizes. The implant performed very
      well - the soft waist filled the aortopulmonary connection and both retention
      discs were properly shaped and pressed against vessel walls. Echocardiogram
      performed 12 hours after the procedure confirmed a correct occluder position. Low
      profile retention discs had no impact on pulmonary valve function, despite the
      defect's proximity to the valve. No obstruction of the aortic or pulmonary artery
      lumen was noted. The Amplatzer Duct Occluder II: Additional Size implant is a
      safe and useful device for percutaneous closure of an aortopulmonary window in a
      carefully selected group of patients.

PMID- 27869055
TI  - Commentary on Aber et al.

PMID- 27869057
TI  - Effect of dam weight and pregnancy nutrition on average lactation performance of
      ewe offspring over 5 years.
AB  - The foetal mammary gland is sensitive to maternal weight and nutrition during
      gestation, which could affect offspring milk production. It has previously been
      shown that ewes born to dams offered maintenance nutrition during pregnancy (day
      21 to 140 of gestation) produced greater milk, lactose and CP yields in their
      first lactation when compared with ewes born to dams offered ad libitum
      nutrition. In addition, ewes born to heavier dams produced greater milk and
      lactose yields when compared with ewes born to lighter dams. The objective of
      this study was to analyse and compare the 5-year lactation performance of the
      previously mentioned ewes, born to heavy or light dams that were offered
      maintenance or ad libitum pregnancy nutrition. Ewes were milked once per week,
      for the first 6 weeks of their lactation, for 5 years. Using milk yield and
      composition data, accumulated yields were calculated over a 42-day period for
      each year for milk, milk fat, CP, true protein, casein and lactose using a
      Legendre orthogonal polynomial model. Over the 5-year period, ewes born to heavy
      dams produced greater average milk (P=0.04), lactose (P=0.01) and CP (P=0.04)
      yields than offspring born to light dams. In contrast, over the 5-year period dam
      nutrition during pregnancy did not affect average (P>0.05) offspring milk yields
      or composition, but did increase milk and lactose accumulated yield (P=0.03 and
      0.01, respectively) in the first lactation. These results indicate that maternal
      gestational nutrition appears to only affect the first lactational performance of
      ewe offspring. Neither dam nutrition nor size affected grand-offspring live
      weight gain to, or live weight at weaning (P>0.05). Combined these data indicate
      that under the conditions of the present study, manipulating dam weight or
      nutrition in pregnancy can have some effects of offspring lactational
      performance, however, these effects are not large enough to alter grand-offspring
      growth to weaning. Therefore, such manipulations are not a viable management tool
      for farmers to influence lamb growth to weaning.

PMID- 27869056
TI  - Why calpain inhibitors are interesting leading compounds to search for new
      therapeutic options to treat leishmaniasis?
AB  - Leishmaniasis is a neglected disease, which needs improvements in drug
      development, mainly due to the toxicity, parasite resistance and low compliance
      of patients to treatment. Therefore, the development of new chemotherapeutic
      compounds is an urgent need. This opinion article will briefly highlight the
      feasible use of calpain inhibitors as leading compounds to search for new
      therapeutic options to treat leishmaniasis. The milestone of this approach is to
      take advantage on the myriad of inhibitors developed against calpains, some of
      which are in advanced clinical trials. The deregulated activity of these enzymes
      is associated with several pathologies, such as strokes, diabetes and Parkinson's
      disease, to name a few. In Leishmania, calpain upregulation has been associated
      to drug resistance and virulence. Whereas the difficulties in developing new
      drugs for neglected diseases are more economical than biotechnological,
      repurposing approach with compounds already approved for clinical use by the
      regulatory agencies can be an interesting shortcut to a successful
      chemotherapeutic treatment for leishmaniasis.

PMID- 27869059
TI  - Site-Specific Preparation of Intact Solid-Liquid Interfaces by Label-Free In Situ
      Localization and Cryo-Focused Ion Beam Lift-Out.
AB  - Scanning transmission electron microscopy (STEM) allows atomic scale
      characterization of solid-solid interfaces, but has seen limited applications to
      solid-liquid interfaces due to the volatility of liquids in the microscope
      vacuum. Although cryo-electron microscopy is routinely used to characterize
      hydrated samples stabilized by rapid freezing, sample thinning is required to
      access the internal interfaces of thicker specimens. Here, we adapt cryo-focused
      ion beam (FIB) "lift-out," a technique recently developed for biological
      specimens, to prepare intact internal solid-liquid interfaces for high-resolution
      structural and chemical analysis by cryo-STEM. To guide the milling process we
      introduce a label-free in situ method of localizing subsurface structures in
      suitable materials by energy dispersive X-ray spectroscopy (EDX). Monte Carlo
      simulations are performed to evaluate the depth-probing capability of the
      technique, and show good qualitative agreement with experiment. We also detail
      procedures to produce homogeneously thin lamellae, which enable nanoscale
      structural, elemental, and chemical analysis of intact solid-liquid interfaces by
      analytical cryo-STEM. This work demonstrates the potential of cryo-FIB lift-out
      and cryo-STEM for understanding physical and chemical processes at solid-liquid
      interfaces.

PMID- 27869058
TI  - Relationship of amotivation to neurocognition, self-efficacy and functioning in
      first-episode psychosis: a structural equation modeling approach.
AB  - BACKGROUND: Better understanding of the complex interplay among key determinants
      of functional outcome is crucial to promoting recovery in psychotic disorders.
      However, this is understudied in the early course of illness. We aimed to examine
      the relationships among negative symptoms, neurocognition, general self-efficacy
      and global functioning in first-episode psychosis (FEP) patients using structural
      equation modeling (SEM). METHOD: Three hundred and twenty-one Chinese patients
      aged 26-55 years presenting with FEP to an early intervention program in Hong
      Kong were recruited. Assessments encompassing symptom profiles, functioning,
      perceived general self-efficacy and a battery of neurocognitive tests were
      conducted. Negative symptom measurement was subdivided into amotivation and
      diminished expression (DE) domain scores based on the ratings in the Scale for
      the Assessment of Negative Symptoms. RESULTS: An initial SEM model showed no
      significant association between functioning and DE which was removed from further
      analysis. A final trimmed model yielded very good model fit (chi2 = 15.48, p =
      0.63; comparative fit index = 1.00; root mean square error of approximation
      <0.001) and demonstrated that amotivation, neurocognition and general self
      efficacy had a direct effect on global functioning. Amotivation was also found to
      mediate a significant indirect effect of neurocognition and general self-efficacy
      on functioning. Neurocognition was not significantly related to general self
      efficacy. CONCLUSION: Our results indicate a critical intermediary role of
      amotivation in linking neurocognitive impairment to functioning in FEP. General
      self-efficacy may represent a promising treatment target for improvement of
      motivational deficits and functional outcome in the early illness stage.

PMID- 27869060
TI  - RECIPROCITY-BUILDING AND THE IMPORTANCE OF INTERDISCIPLINARY COLLABORATION IN
      TUBERCULOSIS RESEARCH.

PMID- 27869061
TI  - CONSIDERING NEOLIBERALISM, CONTEMPT AND ALLOSTATIC LOAD IN THE SOCIAL DYNAMICS OF
      TUBERCULOSIS.

PMID- 27869062
TI  - Is the Polymyxin B Resistance Among Multidrug-Resistant Enterobacteriaceae
      (Except for the Carbapenemase-producing Ones) a Myth or a Matter?

PMID- 27869064
TI  - Transdiagnostic brain responses to disorder-related threat across four
      psychiatric disorders.
AB  - BACKGROUND: There is an ongoing debate whether transdiagnostic neural mechanisms
      are shared by different anxiety-related disorders or whether different disorders
      show distinct neural correlates. To investigate this issue, studies controlling
      for design and stimuli across multiple anxiety-related disorders are needed.
      METHOD: The present functional magnetic resonance imaging study investigated
      neural correlates of visual disorder-related threat processing across unmedicated
      patients suffering from panic disorder (n = 20), social anxiety disorder (n =
      20), dental phobia (n = 16) and post-traumatic stress disorder (n = 11) relative
      to healthy controls (HC; n = 67). Each patient group and the corresponding HC
      group saw a tailor-made picture set with 50 disorder-related and 50 neutral
      scenes. RESULTS: Across all patients, increased activation to disorder-related v.
      neutral scenes was found in subregions of the bilateral amygdala. In addition,
      activation of the lateral amygdala to disorder-related v. neutral scenes
      correlated positively with subjective anxiety ratings of scenes across patients.
      Furthermore, whole-brain analysis revealed increased responses to disorder
      related threat across the four disorders in middle, medial and superior frontal
      regions, (para-)limbic regions, such as the insula and thalamus, as well as in
      the brainstem and occipital lobe. We found no disorder-specific brain responses.
      CONCLUSIONS: The results suggest that pathologically heightened lateral amygdala
      activation is linked to experienced anxiety across anxiety disorders and trauma-
      and stressor-related disorders. Furthermore, the transdiagnostically shared
      activation network points to a common neural basis of abnormal responses to
      disorder-related threat stimuli across the four investigated disorders.

PMID- 27869065
TI  - Effect of organic grass-clover silage on fiber digestion in dairy cows.
AB  - There are differences in grass-clover proportions and chemical composition
      between herbage from primary growth (PG) and regrowth (RG) in grass-clover leys.
      Mixing silages made from PG and RG may provide a more optimal diet to dairy cows
      than when fed separately. We tested the hypotheses that increasing dietary
      proportions of grass-clover silage made from RG compared with PG would increase
      digestion rate of potentially degradable NDF (pdNDF), and increase ruminal
      accumulation of indigestible NDF (iNDF). Eight rumen cannulated Norwegian Red
      cows were used in two replicated 4*4 Latin squares with 21-day periods. Silages
      were prepared from PG and RG of an organically cultivated ley, where PG and RG
      silages were fed ad libitum in treatments with RG replacing PG in ratios of 0,
      0.33, 0.67 and 1 on dry matter basis in addition to 8 kg concentrate. We
      evaluated the effect of the four diets with emphasis on rumen- and total tract
      fiber digestibility. Increasing RG proportions decreased silage intake by 7%.
      Omasal flow of pdNDF decreased, whereas iNDF flow increased with increasing RG
      proportions. Increasing RG proportions decreased rumen pool sizes of NDF and
      pdNDF, whereas pool sizes of iNDF and CP increased. Increasing RG proportions
      increased digestion rate of NDF, which resulted in greater total tract digestion
      of NDF. Pure PG diet had the highest calculated energy intake, but the improved
      rumen digestion of NDF by cows offered 0.33 and 0.67 of RG leveled out milk fat
      and protein yields among the three PG containing diets.

PMID- 27869063
TI  - Screening Patients Undergoing Total Hip or Knee Arthroplasty with Perioperative
      Urinalysis and the Effect of a Practice Change on Antimicrobial Use.
AB  - OBJECTIVE To identify predictors of treatment for urinary tract infections (UTI)
      among patients undergoing total hip (THA) or knee (TKA) arthroplasties and to
      assess an intervention based on these predictors. DESIGN We conducted a
      retrospective cohort study of 200 consecutive patients undergoing THA/TKA between
      February 21, 2011, and June 30, 2011, to identify predictors of treatment for UTI
      and a prospective cohort study of 50 patients undergoing these procedures between
      May 21, 2012, and July 17, 2012, to assess the association of signs or symptoms
      and UTI treatment. We then conducted a before-and-after study to assess whether
      implementing an intervention affected the frequency of treatment for UTI before
      or after THA/TKA. SETTING The orthopedics department of a university health
      center. PATIENTS Patients undergoing THA or TKA. INTERVENTION Surgeons revised
      their UTI screening and treatment practices. RESULTS Positive leukocyte esterase
      (P5 (P=.01; P=.01) were associated with preoperative or postoperative UTI
      treatment. In the prospective study, 12 patients (24%) had signs and symptoms
      consistent with UTI. The number of patients treated for presumed UTI decreased
      80.2% after the surgeons changed their practices, and surgical site infection
      (SSI) rates, including prosthetic joint infections (PJIs), did not increase.
      CONCLUSIONS Urine leukocyte esterase and white blood cell count were the
      strongest predictors of treatment for UTI before or after THA/TKA. The
      intervention was associated with a significant decrease in treatment for UTI, and
      SSI/PJI rates did not increase. Infect Control Hosp Epidemiol 2017;38:281-286.

PMID- 27869066
TI  - Developmental and social-ecological perspectives on children, political violence,
      and armed conflict.
AB  - An increasing number of researchers and policymakers have been moved to study and
      intervene in the lives of children affected by violent conflicts (Masten, 2014).
      According to a United Nations Children's Fund (2009) report, over 1 billion
      children under the age of 18 are growing up in regions where acts of political
      violence and armed conflict are, as Ladds and Cairns (1996, p. 15) put it, "a
      common occurrence-a fact of life." In recent years, the United Nations Children's
      Fund, advocacy and human rights groups, journalists, and researchers have drawn
      public attention to the high rates of child casualties in these regions, and to
      the plights of those children still caught in the crossfire. It has thus become
      clear that both the challenges and the stakes are higher than ever to promote the
      safety and well-being of affected children around the world (Masten & Narayan,
      2012; Tol, Jordans, Kohrt, Betancourt, & Komproe, 2012).

PMID- 27869067
TI  - [The French Society of Myology shows some heart].

PMID- 27869068
TI  - [About the technique of muscle biopsy (III). The contribution of elctron
      microscopy, yesterday, and at the time of the molecular genetics era. A
      historical overview].

PMID- 27869069
TI  - [Unusual phenotype of myopathy associated with a new PNPLA2 mutation].

PMID- 27869070
TI  - ?

PMID- 27869072
TI  - [Tailored orthotic shoes in Charcot-Marie-Tooth disease].

PMID- 27869071
TI  - [Diagnostic orientation of " Rigid spine " familial case with whole body muscle
      MRI].

PMID- 27869073
TI  - ?

PMID- 27869074
TI  - [Respiratory care in patient with neuromuscular disease: the existing and the
      desirable].

PMID- 27869075
TI  - [Cell therapies for cardiopathies: the shift of paradigms].
AB  - Heart failure is a major concern for public health systems, and several
      approaches of cellular therapy are being investigated with the goal of improving
      the function of these failing hearts. Many cell types have been used (skeletal
      myoblasts, hematopoietic, endothelial or mesenchymal progenitors, cardiac
      cells...), most often in the indication of post-ischemic heart failure rather
      than in the indication of genetic dilated cardiomyopathy. It is easier, indeed,
      to target a restricted area than the whole myocardium. Several clinical trials
      have reported slight but encouraging functional benefits, but their
      interpretations were frequently limited by the small sizes of cohorts, and by the
      biological variabilities inherent to the patients status and to the biology of
      the cells. These trials also shed light on unexpected mechanisms of action of the
      cells, which are changing the concepts and methodologies of the studies. The
      functional benefits observed would be due, indeed, to the secretion of trophic
      factors by the cells, instead of their true structural and mechanical integration
      within the myocardial tissue. Accordingly, the new generations of clinical trials
      aim at improving the size and homogeneity of the patient cohorts to increase the
      statistical power. On the other hand, several studies are associating or
      conditionning cells with biomaterials or cocktails of cytokines to improve their
      survival and their biological efficacy. In parallel, bio-engineering investigates
      several ways to support cells in vitro and in vivo, to sustain the architectural
      structure of the failing myocardium, to produce ex vivo some true substitutive
      cardiac tissue, or to purely replace the cells by their active secreted products.
      Several therapeutic devices should emerge from these researches, and the choice
      of their respective use will be ultimately guided by the medical indication.

PMID- 27869076
TI  - [Genes of alpha-dystroglycanopathies in 2016].

PMID- 27869078
TI  - [NeuroMyoGene Institute: a Franco-Canadian partnership promoting research in
      neuromuscular disorders].

PMID- 27869077
TI  - [Finland: an ideally valued genetic heritage].

PMID- 27869079
TI  - ?

PMID- 27869080
TI  - The Effect of Biologically Effective Dose and Radiation Treatment Schedule on
      Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With
      Stereotactic Body Radiation Therapy.
AB  - PURPOSE: To determine the effect of biologically effective dose (BED10) and
      radiation treatment schedule on overall survival (OS) in patients with early
      stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation
      therapy (SBRT). METHODS AND MATERIALS: Using data from 65 treatment centers in
      the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC
      patients undergoing SBRT alone from 2006 to 2014. Biologically relevant
      covariates, including dose per fraction, number of fractions, and time between
      fractions, were used to quantify BED10 and radiation treatment schedule. The
      linear-quadratic equation was used to calculate BED10 and to generate a
      dichotomous dose variable of <105 Gy versus >=105 Gy BED10. The primary outcome
      was OS. We used the Kaplan-Meier method, the log-rank test, and Cox proportional
      hazards regression with propensity score matching to determine whether
      prescription BED10 was associated with OS. RESULTS: We identified 747 patients
      who met inclusion criteria. The median BED10 was 132 Gy, and 59 (7.7%) had
      consecutive-day fractions. Median follow-up was 41 months, and 452 patients
      (60.5%) had died by the conclusion of the study. The 581 patients receiving >=105
      Gy BED10 had a median survival of 28 months, whereas the 166 patients receiving
      <105 Gy BED10 had a median survival of 22 months (log-rank, P=.01). Radiation
      treatment schedule was not a significant predictor of OS on univariable analysis.
      After adjusting for T stage, sex, tumor histology, and Eastern Cooperative
      Oncology Group performance status, BED10 >=105 Gy versus <105 Gy remained
      significantly associated with improved OS (hazard ratio 0.78, 95% confidence
      interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables
      within high- and low-dose cohorts confirmed a survival benefit with higher
      prescription dose. CONCLUSIONS: We found that dose escalation to 105 Gy BED10 and
      beyond may improve survival in NSCLC patients treated with SBRT.

PMID- 27869081
TI  - Long-Term Update of NRG Oncology RTOG 0319: A Phase 1 and 2 Trial to Evaluate 3
      Dimensional Conformal Radiation Therapy Confined to the Region of the Lumpectomy
      Cavity for Stage I and II Breast Carcinoma.
AB  - PURPOSE: NRG Oncology RTOG 0319 was the first cooperative group trial in the
      United States to evaluate 3-dimensional conformal radiation therapy (3D-CRT)
      accelerated partial breast irradiation (APBI). This report updates secondary
      endpoints of toxicity and efficacy. METHODS AND MATERIALS: Patients with stage I
      or II invasive breast cancer (tumor size <=3 cm, <=3 positive lymph nodes,
      negative margins) were eligible for 3D-CRT APBI: 38.5 Gy in 10 twice-daily
      fractions. Patient characteristics and treatment details have previously been
      reported. Adverse events were graded with CTCAE v3.0 (National Cancer Institute
      Common Terminology Criteria for Adverse Events version 3.0). This analysis
      updates the rates of ipsilateral breast recurrence (IBR), contralateral breast
      recurrence, ipsilateral node recurrence (INR), metastatic sites (distant
      metastases [DM]), mastectomy, disease-free survival, mastectomy-free survival,
      and overall survival. RESULTS: Of 58 enrolled patients, 52 were eligible, with a
      median age of 61 years; 94% had stage I cancer and 83% had estrogen receptor
      positive disease. The median follow-up period was 8 years (minimum-maximum, 1.7
      9.0 years). The 7-year estimate of isolated IBR (no DM) was 5.9%. The 7-year
      estimates of all IBRs, INR, mastectomy rate, and DM were 7.7%, 5.8%, 7.7%, and
      7.7%, respectively. All 4 IBRs were invasive, of which 3 had a component within
      the planning target volume. The patterns of failure were as follows: 3 IBRs, 1
      INR, 2 DM, 1 INR plus DM, and 1 IBR plus INR plus DM. The 7-year estimates of
      mastectomy-free survival, disease-free survival, and overall survival were 71.2%,
      71.2%, and 78.8%, respectively. Thirteen patients died: 3 of breast cancer and 10
      of other causes. Grade 3 (G3) treatment-related adverse events were reported by 4
      patients (7.7%). No G3 pain or pulmonary or cardiac toxicities were reported.
      CONCLUSIONS: This phase 1 and 2 trial of 3D-CRT APBI continues to show durable
      tumor control and minimal G3 toxicity, comparable to other APBI techniques.
      Mature phase 3 results will determine the appropriateness and limitations of this
      noninvasive APBI technique.

PMID- 27869083
TI  - Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient
      Spot-Scanning Proton Arc Therapy.
AB  - PURPOSE: To present a novel robust and delivery-efficient spot-scanning proton
      arc (SPArc) therapy technique. METHODS AND MATERIALS: A SPArc optimization
      algorithm was developed that integrates control point resampling, energy layer
      redistribution, energy layer filtration, and energy layer resampling. The
      feasibility of such a technique was evaluated using sample patients: 1 patient
      with locally advanced head and neck oropharyngeal cancer with bilateral lymph
      node coverage, and 1 with a nonmobile lung cancer. Plan quality, robustness, and
      total estimated delivery time were compared with the robust optimized multifield
      step-and-shoot arc plan without SPArc optimization (Arcmulti-field) and the
      standard robust optimized intensity modulated proton therapy (IMPT) plan. Dose
      volume histograms of target and organs at risk were analyzed, taking into account
      the setup and range uncertainties. Total delivery time was calculated on the
      basis of a 360 degrees  gantry room with 1 revolutions per minute gantry rotation
      speed, 2-millisecond spot switching time, 1-nA beam current, 0.01 minimum spot
      monitor unit, and energy layer switching time of 0.5 to 4 seconds. RESULTS: The
      SPArc plan showed potential dosimetric advantages for both clinical sample cases.
      Compared with IMPT, SPArc delivered 8% and 14% less integral dose for
      oropharyngeal and lung cancer cases, respectively. Furthermore, evaluating the
      lung cancer plan compared with IMPT, it was evident that the maximum skin dose,
      the mean lung dose, and the maximum dose to ribs were reduced by 60%, 15%, and
      35%, respectively, whereas the conformity index was improved from 7.6 (IMPT) to
      4.0 (SPArc). The total treatment delivery time for lung and oropharyngeal cancer
      patients was reduced by 55% to 60% and 56% to 67%, respectively, when compared
      with Arcmulti-field plans. CONCLUSION: The SPArc plan is the first robust and
      delivery-efficient proton spot-scanning arc therapy technique, which could
      potentially be implemented into routine clinical practice.

PMID- 27869082
TI  - Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy
      Transfer.
AB  - PURPOSE: We describe a treatment plan optimization method for intensity modulated
      proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in
      critical structures located within or near the target volume while limiting
      degradation of the best possible physical dose distribution. METHODS AND
      MATERIALS: To allow fast optimization based on dose and LET, a GPU-based Monte
      Carlo code was extended to provide dose-averaged LET in addition to dose for all
      pencil beams. After optimizing an initial IMPT plan based on physical dose, a
      prioritized optimization scheme is used to modify the LET distribution while
      constraining the physical dose objectives to values close to the initial plan.
      The LET optimization step is performed based on objective functions evaluated for
      the product of LET and physical dose (LET*D). To first approximation, LET*D
      represents a measure of the additional biological dose that is caused by high
      LET. RESULTS: The method is effective for treatments where serial critical
      structures with maximum dose constraints are located within or near the target.
      We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of
      skull chordomas, ependymomas) in whom the target volume overlaps with the
      brainstem and optic structures. In all cases, high LET*D in critical structures
      could be avoided while minimally compromising physical dose planning objectives.
      CONCLUSION: LET-based reoptimization of IMPT plans represents a pragmatic
      approach to bridge the gap between purely physical dose-based and relative
      biological effectiveness (RBE)-based planning. The method makes IMPT treatments
      safer by mitigating a potentially increased risk of side effects resulting from
      elevated RBE of proton beams near the end of range.

PMID- 27869085
TI  - In Reply to Fodor and Di Muzio.

PMID- 27869086
TI  - In Regard to Perrier et al.

PMID- 27869084
TI  - Verification of Dose Distribution in Carbon Ion Radiation Therapy for Stage I
      Lung Cancer.
AB  - PURPOSE: To evaluate robustness of dose distribution of carbon-ion radiation
      therapy (C-ion RT) in non-small cell lung cancer (NSCLC) and to identify factors
      affecting the dose distribution by simulated dose distribution. METHODS AND
      MATERIALS: Eighty irradiation fields for delivery of C-ion RT were analyzed in 20
      patients with stage I NSCLC. Computed tomography images were obtained twice
      before treatment initiation. Simulated dose distribution was reconstructed on
      computed tomography for confirmation under the same settings as actual treatment
      with respiratory gating and bony structure matching. Dose-volume histogram
      parameters, such as %D95 (percentage of D95 relative to the prescribed dose),
      were calculated. Patients with any field for which the %D95 of gross tumor volume
      (GTV) was below 90% were classified as unacceptable for treatment, and the
      optimal target margin for such cases was examined. RESULTS: Five patients with a
      total of 8 fields (10% of total number of fields analyzed) were classified as
      unacceptable according to %D95 of GTV, although most patients showed no
      remarkable change in the dose-volume histogram parameters. Receiver operating
      characteristic curve analysis showed that tumor displacement and change in water
      equivalent pathlength were significant predictive factors of unacceptable cases
      (P<.001 and P=.002, respectively). The main cause of degradation of the dose
      distribution was tumor displacement in 7 of the 8 unacceptable fields. A 6-mm
      planning target volume margin ensured a GTV %D95 of >90%, except in 1 extremely
      unacceptable field. CONCLUSIONS: According to this simulation analysis of C-ion
      RT for stage I NSCLC, a few fields were reported as unacceptable and required
      resetting of body position and reconfirmation. In addition, tumor displacement
      and change in water-equivalent pathlength (bone shift and/or chest wall
      thickness) were identified as factors influencing the robustness of dose
      distribution. Such uncertainties should be regarded in planning.

PMID- 27869087
TI  - In Regard to Zietman et al.

PMID- 27869088
TI  - In Reply to Samaratunga et al.

PMID- 27869089
TI  - In Regard to Baumann et al.

PMID- 27869090
TI  - In Reply to Leung.

PMID- 27869091
TI  - In Reply to Tini et al.

PMID- 27869092
TI  - Erratum to: Baumann BC, Bosch WR, Bahl A, et al. Development and validation of
      consensus contouring guidelines for adjuvant radiation therapy for bladder cancer
      after radical cystectomy. Int J Radiat Oncol Biol Phys 2016;96:78-86.

PMID- 27869093
TI  - Early-Stage Lung Cancer, Surgery, and Stereotactic Body Radiation Therapy:
      Quality of Life.

PMID- 27869094
TI  - Transformative Technologies: The Crookes, Coolidge, and Cascade Tubes.

PMID- 27869095
TI  - Does Heavy Ion Therapy Work Through the Immune System?

PMID- 27869096
TI  - Predictive Factor Analysis of Response-Adapted Radiation Therapy for Chemotherapy
      Sensitive Pediatric Hodgkin Lymphoma: Analysis of the Children's Oncology Group
      AHOD 0031 Trial.
AB  - PURPOSE: To evaluate whether clinical risk factors could further distinguish
      children with intermediate-risk Hodgkin lymphoma (HL) with rapid early and
      complete anatomic response (RER/CR) who benefit significantly from involved-field
      RT (IFRT) from those who do not, and thereby aid refinement of treatment
      selection. METHODS AND MATERIALS: Children with intermediate-risk HL treated on
      the Children's Oncology Group AHOD 0031 trial who achieved RER/CR with 4 cycles
      of chemotherapy, and who were randomized to 21-Gy IFRT or no additional therapy
      (n=716) were the subject of this study. Recursive partitioning analysis was used
      to identify factors associated with clinically and statistically significant
      improvement in event-free survival (EFS) after randomization to IFRT. Bootstrap
      sampling was used to evaluate the robustness of the findings. RESULT: Although
      most RER/CR patients did not benefit significantly from IFRT, those with a
      combination of anemia and bulky limited-stage disease (n=190) had significantly
      better 4-year EFS with the addition of IFRT (89.3% vs 77.9% without IFRT;
      P=.019); this benefit was consistently reproduced in bootstrap analyses and after
      adjusting for other prognostic factors. CONCLUSION: Although most patients
      achieving RER/CR had favorable outcomes with 4 cycles of chemotherapy alone,
      those children with initial bulky stage I/II disease and anemia had significantly
      better EFS with the addition of IFRT as part of combined-modality therapy.
      Further work evaluating the interaction of clinical and biologic factors and
      imaging response is needed to further optimize and refine treatment selection.

PMID- 27869097
TI  - The Impact of Radiation Treatment Time on Survival in Patients With Head and Neck
      Cancer.
AB  - PURPOSE: To assess the impact of radiation treatment time (RTT) in head and neck
      cancers on overall survival (OS) in the era of chemoradiation. METHODS AND
      MATERIALS: Patients with diagnoses of tongue, hypopharynx, larynx, oropharynx, or
      tonsil cancer were identified by use of the National Cancer Database. RTT was
      defined as date of first radiation treatment to date of last radiation treatment.
      In the definitive setting, prolonged RTT was defined as >56 days, accelerated RTT
      was defined as <47 days, and standard RTT was defined as 47 to 56 days. In the
      postoperative setting, prolonged RTT was defined as >49 days, accelerated RTT was
      defined as <40 days, and standard RTT was defined as 40 to 49 days. We used chi2
      tests to identify predictors of RTT. The Kaplan-Meier method was used to compare
      OS among groups. Cox proportional hazards model was used for OS analysis in
      patients with known comorbidity status. RESULTS: 19,531 patients were included;
      12,987 (67%) had a standard RTT, 4,369 (34%) had an accelerated RTT, and 2,165
      (11%) had a prolonged RTT. On multivariable analysis, accelerated RTT (hazard
      ratio [HR] 0.84; 95% confidence interval [CI] 0.73-0.97) was associated with an
      improved OS, and prolonged RTT (HR 1.25; 95% CI 1.14-1.37) was associated with a
      worse OS relative to standard RTT. When the 9,200 (47%) patients receiving
      definitive concurrent chemoradiation were examined, prolonged RTT (HR 1.29; 95%
      CI 1.11-1.50) was associated with a worse OS relative to standard RTT, whereas
      there was no significant association between accelerated RTT and OS (HR 0.76; 95%
      CI 0.57-1.01). CONCLUSION: Prolonged RTT is associated with worse OS in patients
      receiving radiation therapy for head and neck cancer, even in the setting of
      chemoradiation. Expeditious completion of radiation should continue to be a
      quality metric for the management of head and neck malignancies.

PMID- 27869099
TI  - Photo-sensitive mycosis fungoides: a new variant?

PMID- 27869098
TI  - Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis
      of the National Cancer Data Base, 2004 to 2012.
AB  - PURPOSE: To evaluate the effect of radiation dose escalation on overall survival
      (OS) for patients with nonmetastatic esophageal cancer treated with concurrent
      radiation and chemotherapy. METHODS AND MATERIALS: Patients diagnosed with stage
      I to III esophageal cancer treated from 2004 to 2012 were identified from the
      National Cancer Data Base. Patients who received concurrent radiation and
      chemotherapy with radiation doses of >=50 Gy and did not undergo surgery were
      included. OS was compared using Cox proportional hazards regression and
      propensity score matching. RESULTS: A total of 6854 patients were included; 3821
      (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy.
      Univariate analysis revealed no significant difference in OS between patients
      receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis,
      binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable
      difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses
      investigating the effect of dose escalation by histologic type and in the setting
      of intensity modulated radiation therapy also failed to reveal a benefit.
      Propensity score matching confirmed the absence of a statistically significant
      difference in OS among the dose levels. The factors associated with improved OS
      on multivariable analysis included female sex, lower Charlson-Deyo comorbidity
      score, private insurance, cervical/upper esophagus location, squamous cell
      histologic type, lower T stage, and node-negative status (P<.01 for all
      analyses). CONCLUSIONS: In this large national cohort, dose escalation >50.4 Gy
      did not result in improved OS among patients with stage I to III esophageal
      cancer treated with definitive concurrent radiation and chemotherapy. These data
      suggest that despite advanced contemporary treatment techniques, OS for patients
      with esophageal cancer remains unaltered by escalation of radiation dose >50.4
      Gy, consistent with the results of the INT-0123 trial. Furthermore, these data
      highlight that many radiation oncologists have not embraced the concept that dose
      escalation does not improve OS. Although local control, not investigated in the
      present study, might benefit from dose escalation, novel therapies are needed to
      improve the OS of patients with esophageal cancer.

PMID- 27869100
TI  - The effects of magnesium supplementation on subjective anxiety.
AB  - : Experimental studies of anxiety in animal models, and evidence of efficacious
      outcomes of magnesium (Mg) supplementation in the treatment of acute clinical
      affective disorders, has increased interest in Mg as a potential novel treatment
      for symptoms of mild/moderate subjective anxiety. This short review examines the
      existing evidence for the effects of Mg supplementation on subjective anxiety in
      humans. Additionally, evidence from three unpublished studies that examined Mg
      and vitamin B6 intake on subjective anxiety is summarised to supplement the
      existing literature. CONCLUSIONS: The efficacy of Mg in the treatment of anxiety
      in the mildly anxious and those reporting premenstrual syndrome-related anxiety
      is suggestive of a beneficial effect of Mg intake. Further randomised controlled
      trials are warranted to further establish the efficacy of Mg as a novel treatment
      for subjective anxiety.

PMID- 27869101
TI  - A stacked contractive denoising auto-encoder for ECG signal denoising.
AB  - As a primary diagnostic tool for cardiac diseases, electrocardiogram (ECG)
      signals are often contaminated by various kinds of noise, such as baseline
      wander, electrode contact noise and motion artifacts. In this paper, we propose a
      contractive denoising technique to improve the performance of current denoising
      auto-encoders (DAEs) for ECG signal denoising. Based on the Frobenius norm of the
      Jacobean matrix for the learned features with respect to the input, we develop a
      stacked contractive denoising auto-encoder (CDAE) to build a deep neural network
      (DNN) for noise reduction, which can significantly improve the expression of ECG
      signals through multi-level feature extraction. The proposed method is evaluated
      on ECG signals from the bench-marker MIT-BIH Arrhythmia Database, and the noises
      come from the MIT-BIH noise stress test database. The experimental results show
      that the new CDAE algorithm performs better than the conventional ECG denoising
      method, specifically with more than 2.40 dB improvement in the signal-to-noise
      ratio (SNR) and nearly 0.075 to 0.350 improvements in the root mean square error
      (RMSE).

PMID- 27869102
TI  - Novel injectable, self-gelling hydrogel-microparticle composites for bone
      regeneration consisting of gellan gum and calcium and magnesium carbonate
      microparticles.
AB  - The suitability of hydrogel biomaterials for bone regeneration can be improved by
      incorporation of an inorganic phase in particle form, thus maintaining hydrogel
      injectability. In this study, carbonate microparticles containing different
      amounts of calcium (Ca) and magnesium (Mg) were added to solutions of the anionic
      polysaccharide gellan gum (GG) to crosslink GG by release of Ca2+ and Mg2+ from
      microparticles and thereby induce formation of hydrogel-microparticle composites.
      It was hypothesized that increasing Mg content of microparticles would promote GG
      hydrogel formation. The effect of Mg incorporation on cytocompatibility and cell
      growth was also studied. Microparticles were formed by mixing Ca2+ and Mg2+ and
      [Formula: see text] ions in varying concentrations. Microparticles were
      characterized physiochemically and subsequently mixed with GG solution to form
      hydrogel-microparticle composites. The elemental Ca:Mg ratio in the mineral
      formed was similar to the Ca:Mg ratio of the ions added. In the absence of Mg,
      vaterite was formed. At low Mg content, magnesian calcite was formed. Increasing
      the Mg content further caused formation of amorphous mineral. Microparticles of
      vaterite and magnesium calcite did not induce GG hydrogel formation, but addition
      of Mg-richer amorphous microparticles induced gelation within 20 min.
      Microparticles were dispersed homogeneously in hydrogels. MG-63 osteoblast-like
      cells were cultured in eluate from hydrogel-microparticle composites and on the
      composites themselves. All composites were cytocompatible. Cell growth was
      highest on composites containing particles with an equimolar Ca:Mg ratio. In
      summary, carbonate microparticles containing a sufficient amount of Mg induced GG
      hydrogel formation, resulting in injectable, cytocompatible hydrogel
      microparticle composites.

PMID- 27869103
TI  - Th-17 cytokines and interstitial lung involvement in systemic sclerosis.
AB  - The two phenotypes of both limited and diffuse systemic sclerosis (SSc) have
      different forms of pulmonary involvement: pulmonary arterial hypertension
      (limited phenotype) or interstitial lung disease (ILD) (diffuse phenotype). We
      aimed to investigate whether Th17-related cytokines, as measured in exhaled
      breath condensate (EBC) and in serum were connected to ILD in diffuse SSc
      patients. We found that for both limited and diffuse SSc, the EBC levels of all
      cytokines and most of the cytokine serum levels were significantly higher in
      patients than in controls, while, the EBC levels of Th-17 cytokines and the serum
      levels of IL-10 and TNF-alpha were significantly higher in diffuse than in
      limited SSc. Moreover, the thoracic CT-scan score of ILD was significantly
      associated with the EBC levels of IL-1 beta and with the serum IL-23, TNF-alpha
      and IL-10 levels, whereas lung carbon monoxide diffusing capacity was negatively
      related to the EBC levels of IL-1 beta, IL-17 and serum IL-10. Serum IL-23 was
      also inversely correlated with vital capacity. In conclusion, in diffuse SSc
      patients our results show a clear link between Th-17 cytokines measured both in
      EBC and in serum with interstitial lung involvement. This highlights how
      important it is to target Th-17 cytokines when developing new treatments for lung
      fibrosis.

PMID- 27869104
TI  - Comparative analysis of the volatile metabolomes of Pseudomonas aeruginosa
      clinical isolates.
AB  - Pseudomonas aeruginosa is a nearly ubiquitous Gram-negative organism, well known
      to occupy a multitude of environmental niches and cause human infections at a
      variety of bodily sites, due to its metabolic flexibility, secondary to extensive
      genetic heterogeneity at the species level. Because of its dynamic metabolism and
      clinical importance, we sought to perform a comparative analysis on the volatile
      metabolome (the 'volatilome') produced by P. aeruginosa clinical isolates. In
      this study, we analyzed the headspace volatile molecules of 24 P. aeruginosa
      clinical isolates grown in vitro, using 2D gas chromatography time-of-flight mass
      spectrometry (GC  *  GC-TOFMS). We identified 391 non-redundant compounds that we
      associate with the growth and metabolism of P. aeruginosa (the 'pan-volatilome').
      Of these, 70 were produced by all 24 isolates (the 'core volatilome'), 52 by only
      a single isolate, and the remaining 269 volatile molecules by a subset. Sixty
      five of the detected compounds could be assigned putative compound
      identifications, of which 43 had not previously been associated with P.
      aeruginosa. Using the accessory volatile molecules, we determined the inter
      strain variation in the metabolomes of these isolates, clustering strains by
      their metabotypes. Assessing the extent of metabolomic diversity in P. aeruginosa
      through an analysis of the volatile molecules that it produces is a critical next
      step in the identification of novel diagnostic or prognostic biomarkers.

PMID- 27869105
TI  - An open access database for the evaluation of heart sound algorithms.
AB  - In the past few decades, analysis of heart sound signals (i.e. the
      phonocardiogram or PCG), especially for automated heart sound segmentation and
      classification, has been widely studied and has been reported to have the
      potential value to detect pathology accurately in clinical applications. However,
      comparative analyses of algorithms in the literature have been hindered by the
      lack of high-quality, rigorously validated, and standardized open databases of
      heart sound recordings. This paper describes a public heart sound database,
      assembled for an international competition, the PhysioNet/Computing in Cardiology
      (CinC) Challenge 2016. The archive comprises nine different heart sound databases
      sourced from multiple research groups around the world. It includes 2435 heart
      sound recordings in total collected from 1297 healthy subjects and patients with
      a variety of conditions, including heart valve disease and coronary artery
      disease. The recordings were collected from a variety of clinical or nonclinical
      (such as in-home visits) environments and equipment. The length of recording
      varied from several seconds to several minutes. This article reports detailed
      information about the subjects/patients including demographics (number, age,
      gender), recordings (number, location, state and time length), associated
      synchronously recorded signals, sampling frequency and sensor type used. We also
      provide a brief summary of the commonly used heart sound segmentation and
      classification methods, including open source code provided concurrently for the
      Challenge. A description of the PhysioNet/CinC Challenge 2016, including the main
      aims, the training and test sets, the hand corrected annotations for different
      heart sound states, the scoring mechanism, and associated open source code are
      provided. In addition, several potential benefits from the public heart sound
      database are discussed.

PMID- 27869106
TI  - Computerized wheeze detection in young infants: comparison of signals from
      tracheal and chest wall sensors.
AB  - Computerized wheeze detection is an established method for objective assessment
      of respiratory sounds. In infants, this method has been used to detect
      subclinical airway obstruction and to monitor treatment effects. The optimal
      location for the acoustic sensors, however, is unknown. The aim of this study was
      to evaluate the quality of respiratory sound recordings in young infants, and to
      determine whether the position of the sensor affected computerized wheeze
      detection. Respiratory sounds were recorded over the left lateral chest wall and
      the trachea in 112 sleeping infants (median postmenstrual age: 49 weeks) on 129
      test occasions using an automatic wheeze detection device (PulmoTrack(r)). Each
      recording lasted 10 min and the recordings were stored. A trained clinician
      retrospectively evaluated the recordings to determine sound quality and
      disturbances. The wheeze rates of all undisturbed tracheal and chest wall signals
      were compared using Bland-Altman plots. Comparison of wheeze rates measured over
      the trachea and the chest wall indicated strong correlation (r  ?  0.93, p  < 
      0.001), with a bias of 1% or less and limits of agreement of within 3% for the
      inspiratory wheeze rate and within 6% for the expiratory wheeze rate. However,
      sounds from the chest wall were more often affected by disturbances than sounds
      from the trachea (23% versus 6%, p  <  0.001). The study suggests that in young
      infants, a better quality of lung sound recordings can be obtained with the
      tracheal sensor.

PMID- 27869107
TI  - Studies on the potential risk of amyloidosis from exposure to silk fibroin.
AB  - Amyloid A (AA) amyloidosis can be induced by the administration of amyloid
      fibrils to animals under inflammatory conditions. Silk fibroin (SF) is a main
      component protein of bombic silk and has amyloid-like features. The
      amyloidogenesis of SF solution in mice has been previously reported. Recently,
      the biochemical properties of silk have attracted increasing attention, and
      research and development have been undertaken regarding applications other than
      as a clothing material. However, the risk of AA amyloidosis from exposure to SF
      related products is unknown. In this study, we examined the amyloidogenesis of
      several SF-related products that vary in preparation method or route of injection
      in a mouse model of amyloidosis. The results revealed that amyloid deposits were
      rarely observed in mice exposed to SF solution or feed supplemented with SF
      powder. On the other hand, heavy amyloid deposits were observed in some mice
      implanted with SF non-woven fabric by abdominal operation. Congo red staining of
      SF solutions under polarized light and electron microscopy indicated that SF
      solution in this study had no amyloid-like structures. We found that SF-related
      products occasionally promote amyloidogenesis, but have a low potential for
      amyloidosis.

PMID- 27869109
TI  - Effect of red dyes on blue light phototoxicity against VSC producing bacteria in
      an experimental oral biofilm.
AB  - Oral malodour is considered to be caused mainly by the production of volatile
      sulfide compounds (VSC) by anaerobic Gram-negative oral bacteria. Previous study
      showed that these bacteria were susceptible to blue light (wavelengths of 400-500
      nm). In the present study, we tested the effect of blue light in the presence of
      red dyes on malodour production in an experimental oral biofilm. Biofilms were
      exposed to a plasma-arc light source for 30, 60, and 120 s (i.e. fluences of 41,
      82, and 164 J cm-2, respectively) with the addition of erythrosine, natural red
      and rose bengal (0.01, 0.1 and 1% w/v). Following light exposure biofilm samples
      were examined for malodour production (Odour judge), VSC production
      (HalimeterTM), VSC producing bacteria quantification using microscopy sulfide
      assay (MSA) and reactive oxygen species (ROS) production. Results showed that the
      exposure of experimental oral biofilm to blue light in the presence of rose
      bengal caused an increased reduction in VSC and malodour production concomitant
      with an increase in ROS production. These results suggest that rose bengal might
      be effective as a blue light photosensitizer against VSC producing bacteria.

PMID- 27869110
TI  - Volatile organic compound markers of psychological stress in skin: a pilot study.
AB  - The forehead was studied as a possible sampling site for capturing changes in
      volatile organic compound (VOC) profiles associated with psychological-stress.
      Skin-VOCs were sampled with a polydimethylsilicone (PDMS)-coupon and the
      resulting VOCs were recovered and analysed with two-stage thermal desorption gas
      chromatography-mass spectrometry. Fifteen young adult volunteers (19 years-26
      years) participated in two interventions run in a randomised crossover design.
      One intervention, termed 'Neutral', required the participants to listen to
      peaceful music, the other, termed a 'paced audio serial addition task', required
      the participants to undertake a series of rapid mental arithmetic calculations in
      a challenging environment that induced a stress response. Skin-VOC samples were
      taken during each intervention. The resultant data were processed with dynamic
      background compensation, deconvolved, and registered to a common retention index
      scale. The importance of freezing skin patch samplers to  -80  degrees C was
      determined during the method development phase of this study. The cumulative
      distribution function of the GC-MS data indicates the possibility that PDMS
      coupons are selective towards the lower volatility VOC components in skin. The
      frequency distribution of the GC-MS data was observed to be approximately log
      normal, and on the basis of this study, a further two-orders of magnitude
      reduction in sensitivity may be required before the complete skin-VOC profile may
      be characterised. Multi-variate analysis involving Pareto-scaling prior to
      partial least squares discriminant analysis identified four VOCs with the highest
      probability of contributing to the variance between the two states, and the
      responses to these VOCs were modelled with principle components analysis (PCA).
      Two VOCs, benzoic acid and n-decanoic acid were upregulated (14 and 8 fold
      respectively) and appear to be PASAT sensitive, with areas under (AUC) their
      receiver operator characteristic (ROC) curves of 0.813 and 0.852 respectively. A
      xylene isomer and 3-carene were down regulated 75% and 97% respectively, and
      found to be predictive of the neutral intervention (ROC AUC values of 0.898 and
      0.929 respectively). VOC profiles in skin appear to change with stress either due
      to increased elimination, elevated bacterial activity, or perhaps increased
      oxidative pathways.

PMID- 27869108
TI  - Limonene in exhaled breath is elevated in hepatic encephalopathy.
AB  - Breath samples were taken from 31 patients with liver disease and 30 controls in
      a clinical setting and proton transfer reaction quadrupole mass spectrometry (PTR
      Quad-MS) used to measure the concentration of volatile organic compounds (VOCs).
      All patients had cirrhosis of various etiologies, with some also suffering from
      hepatocellular cancer (HCC) and/or hepatic encephalopathy (HE). Breath limonene
      was higher in patients with No-HCC than with HCC, median (lower/upper quartile)
      14.2 (7.2/60.1) versus 3.6 (2.0/13.7) and 1.5 (1.1/2.3) nmol mol-1 in controls.
      This may reflect disease severity, as those with No-HCC had significantly higher
      UKELD (United Kingdom model for End stage Liver Disease) scores. Patients with HE
      were categorized as having HE symptoms presently, having a history but no current
      symptoms and having neither history nor current symptoms. Breath limonene in
      these groups was median (lower/upper quartile) 46.0 (14.0/103), 4.2 (2.6/6.4) and
      7.2 (2.0/19.1) nmol mol-1, respectively. The higher concentration of limonene in
      those with current symptoms of HE than with a history but no current symptoms
      cannot be explained by disease severity as their UKELD scores were not
      significantly different. Longitudinal data from two patients admitted to hospital
      with HE show a large intra-subject variation in breath limonene, median (range)
      18 (10-44) and 42 (32-58) nmol mol-1.

PMID- 27869111
TI  - Determination of Genotoxic Effects of Hookah Smoking by Micronucleus and
      Chromosome Aberration Methods.
AB  - BACKGROUND Use of a hookah (a type of water pipe) is a traditional way of smoking
      tobacco, particularly in the Middle East. In Turkey, its popularity has been
      growing in recent years, especially among young people. It is known that
      cigarette smoking has genotoxic effects and causes mutations, but no
      comprehensive study has been done on the genotoxic effects of hookah usage,
      particularly in Turkey. MATERIAL AND METHODS We collected peripheral blood/buccal
      smear samples from 30 subjects who did not smoke cigarettes but who regularly
      smoke a hookah an average of 2 times per week, and from 30 control subjects who
      had never smoked cigarettes or a hookah. Chromosome analyses were performed on
      the samples obtained from peripheral blood of each individual, 25 metaphase
      plaques were counted for each, and chromosome/chromatid breakage/gap parameters
      were evaluated. Micronucleus analysis was done on buccal smear samples and
      micronucleus/binucleus parameters were investigated by counting 2000 cells of
      each individual. RESULTS Chromosome breakage ratios were found to be 0.64+/-0.86
      and 0.46+/-0.71 in the study and control groups, respectively, while chromatid
      breakage ratios were 0.53+/-0.83 and 0.53+/-0.71; fragment ratios were 0.82+/
      1.24 and 0.21+/-0.49 (p<0.05); and gap ratios were 0.57+/-0.83 and 0.18+/-0.53
      (p<0.05), respectively. Micronucleus ratio was 6.03+/-2.06 and 4.43+/-2.27
      (p<0.05) in the study and control groups, respectively, and binucleus ratios were
      8.53+/-3.23 and 12.15+/-5.18, respectively (p<0.05). CONCLUSIONS Results of our
      study reveal significant statistical differences between the individuals who
      smoked hookah and those who did not in terms of fragment, gap, micronucleus, and
      binucleus parameters, suggesting that smoking a hookah may cause genotoxic
      effects.

PMID- 27869112
TI  - A Brief Overview of English Primary Care in the Last Half Century.
AB  - Key hefts, the hard core of clinical profile, scientific nursing and nowadays of
      the English School of Primary Care in the last sixty years are revisited. We
      understand that the most profound intellectual influence has been to Archie
      Cochrane, among family physicians hard core components we include John Fry (1922
      1994), David Metcalfe and Julian Tudor Hart. On the other hand, Lisbeth Hockey
      (1918-2004), PhD in Nursing, was responsible for several years of Nursing
      Research Unit at the University of Edinburgh. The internet sources of English
      nursing historical research are very noticeable. Finally, Trisha Greenhalgh,
      family physician, researcher and Professor at the University of Oxford, is
      launching the old English School of Primary Care towards the middle of the XXI
      century.

PMID- 27869113
TI  - Effects of High Intensity Interval Training on Fat Mass Parameters in
      Adolescents.
AB  - OBJECTIVE: Childhood and adolescence are key to the development of chronic
      disease stages, the distribution of fat an important factor in this regard. The
      aim of the study was to evaluate the effects on fat parameters of a high
      intensity program developed in adolescents during physical education classes.
      METHODS: In 2013, 35 school-age children of Caceres taken part in this study
      divided into two groups. The high-intensity group performed for 8 weeks, 4-6 sets
      of 20 seconds at maximal intensity with a ratio effort / recovery of 1: 3 to 1:
      1. The other group, developed continuous aerobic exercise during the same time.
      It conducted an assessment of fat mass before and after the training program.
      Repeated measures ANOVA test was used to observe that there were no statistically
      significant differences. RESULTS: Continuous aerobic training group showed
      statistically significant differences in intra-group analysis in the percentage
      of fat mass trunk (Pre: 15.66 +/- 4.16 vs Post: 16.95 +/- 4.03; +1, 29%; p =
      0.04) and the percentage of total fat (Pre: 21.58 +/- 3.93 / Post: 22.34 +/-
      3.70; p = 0.05). Statistically significant differences were not found in the
      analysis between-groups in any of the studied variables. CONCLUSIONS: The
      training program high intensity physical activity at school carried out during
      physical education classes did not improve fat mass parameters evaluated.
      However, maintaining these parameters could be a good result during the
      development of this stage, where an increase of these occurs.

PMID- 27869114
TI  - A radial map of multi-whisker correlation selectivity in the rat barrel cortex.
AB  - In the barrel cortex, several features of single-whisker stimuli are organized in
      functional maps. The barrel cortex also encodes spatio-temporal correlation
      patterns of multi-whisker inputs, but so far the cortical mapping of neurons
      tuned to such input statistics is unknown. Here we report that layer 2/3 of the
      rat barrel cortex contains an additional functional map based on neuronal tuning
      to correlated versus uncorrelated multi-whisker stimuli: neuron responses to
      uncorrelated multi-whisker stimulation are strongest above barrel centres,
      whereas neuron responses to correlated and anti-correlated multi-whisker
      stimulation peak above the barrel-septal borders, forming rings of multi-whisker
      synchrony-preferring cells.

PMID- 27869115
TI  - Cerebral vascular amyloid seeds drive amyloid beta-protein fibril assembly with a
      distinct anti-parallel structure.
AB  - Cerebrovascular accumulation of amyloid beta-protein (Abeta), a condition known
      as cerebral amyloid angiopathy (CAA), is a common pathological feature of
      patients with Alzheimer's disease. Familial Abeta mutations, such as Dutch-E22Q
      and Iowa-D23N, can cause severe cerebrovascular accumulation of amyloid that
      serves as a potent driver of vascular cognitive impairment and dementia. The
      distinctive features of vascular amyloid that underlie its unique pathological
      properties remain unknown. Here, we use transgenic mouse models producing CAA
      mutants (Tg-SwDI) or overproducing human wild-type Abeta (Tg2576) to demonstrate
      that CAA-mutant vascular amyloid influences wild-type Abeta deposition in brain.
      We also show isolated microvascular amyloid seeds from Tg-SwDI mice drive
      assembly of human wild-type Abeta into distinct anti-parallel beta-sheet fibrils.
      These findings indicate that cerebrovascular amyloid can serve as an effective
      scaffold to promote rapid assembly and strong deposition of Abeta into a unique
      structure that likely contributes to its distinctive pathology.

PMID- 27869116
TI  - Autophagy controls centrosome number by degrading Cep63.
AB  - Centrosome number is associated with the chromosome segregation and genomic
      stability. The ubiquitin-proteasome system is considered to be the main regulator
      of centrosome number. However, here we show that autophagy also regulates the
      number of centrosomes. Autophagy-deficient cells carry extra centrosomes. The
      autophagic regulation of centrosome number is dependent on a centrosomal protein
      of 63 (Cep63) given that cells lacking autophagy contain multiple Cep63 dots that
      are engulfed and digested by autophagy in wild-type cells, and that the
      upregulation of Cep63 increases centrosome number. Cep63 is recruited to
      autophagosomes via interaction with p62, a molecule crucial for selective
      autophagy. In vivo, hematopoietic cells from autophagy-deficient and p62-/- mice
      also contained multiple centrosomes. These results indicate that autophagy
      controls centrosome number by degrading Cep63.

PMID- 27869119
TI  - Mid-infrared ultra-high-Q resonators based on fluoride crystalline materials.
AB  - The unavailability of highly transparent materials in the mid-infrared has been
      the main limitation in the development of ultra-sensitive molecular sensors or
      cavity-based spectroscopy applications. Whispering gallery mode microresonators
      have attained ultra-high-quality (Q) factor resonances in the near-infrared and
      visible. Here we report ultra-high Q factors in the mid-infrared using polished
      alkaline earth metal fluoride crystals. Using an uncoated chalcogenide tapered
      fibre as a high-ideality coupler in the mid-infrared, we study via cavity
      ringdown technique the losses of BaF2, CaF2, MgF2 and SrF2 microresonators. We
      show that MgF2 is limited by multiphonon absorption by studying the temperature
      dependence of the Q factor. In contrast, in SrF2 and BaF2 the lower multiphonon
      absorption leads to ultra-high Q factors at 4.5 MUm. These values correspond to
      an optical finesse of , the highest value achieved for any type of mid-infrared
      resonator to date.

PMID- 27869118
TI  - De-novo protein function prediction using DNA binding and RNA binding proteins as
      a test case.
AB  - Of the currently identified protein sequences, 99.6% have never been observed in
      the laboratory as proteins and their molecular function has not been established
      experimentally. Predicting the function of such proteins relies mostly on
      annotated homologs. However, this has resulted in some erroneous annotations, and
      many proteins have no annotated homologs. Here we propose a de-novo function
      prediction approach based on identifying biophysical features that underlie
      function. Using our approach, we discover DNA and RNA binding proteins that
      cannot be identified based on homology and validate these predictions
      experimentally. For example, FGF14, which belongs to a family of secreted growth
      factors was predicted to bind DNA. We verify this experimentally and also show
      that FGF14 is localized to the nucleus. Mutating the predicted binding site on
      FGF14 abrogated DNA binding. These results demonstrate the feasibility of
      automated de-novo function prediction based on identifying function-related
      biophysical features.

PMID- 27869117
TI  - Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in
      endothelial cells.
AB  - In humans and animals lacking functional LDL receptor (LDLR), LDL from plasma
      still readily traverses the endothelium. To identify the pathways of LDL uptake,
      a genome-wide RNAi screen was performed in endothelial cells and cross-referenced
      with GWAS-data sets. Here we show that the activin-like kinase 1 (ALK1) mediates
      LDL uptake into endothelial cells. ALK1 binds LDL with lower affinity than LDLR
      and saturates only at hypercholesterolemic concentrations. ALK1 mediates uptake
      of LDL into endothelial cells via an unusual endocytic pathway that diverts the
      ligand from lysosomal degradation and promotes LDL transcytosis. The endothelium
      specific genetic ablation of Alk1 in Ldlr-KO animals leads to less LDL uptake
      into the aortic endothelium, showing its physiological role in endothelial
      lipoprotein metabolism. In summary, identification of pathways mediating LDLR
      independent uptake of LDL may provide unique opportunities to block the
      initiation of LDL accumulation in the vessel wall or augment hepatic LDLR
      dependent clearance of LDL.

PMID- 27869120
TI  - The influence of large cations on the electrochemical properties of tunnel
      structured metal oxides.
AB  - Metal oxides with a tunnelled structure are attractive as charge storage
      materials for rechargeable batteries and supercapacitors, since the tunnels
      enable fast reversible insertion/extraction of charge carriers (for example,
      lithium ions). Common synthesis methods can introduce large cations such as
      potassium, barium and ammonium ions into the tunnels, but how these cations
      affect charge storage performance is not fully understood. Here, we report the
      role of tunnel cations in governing the electrochemical properties of electrode
      materials by focusing on potassium ions in alpha-MnO2. We show that the presence
      of cations inside 2 * 2 tunnels of manganese dioxide increases the electronic
      conductivity, and improves lithium ion diffusivity. In addition, transmission
      electron microscopy analysis indicates that the tunnels remain intact whether
      cations are present in the tunnels or not. Our systematic study shows that cation
      addition to alpha-MnO2 has a strong beneficial effect on the electrochemical
      performance of this material.

PMID- 27869121
TI  - Direct identification of clinically relevant neoepitopes presented on native
      human melanoma tissue by mass spectrometry.
AB  - Although mutations may represent attractive targets for immunotherapy, direct
      identification of mutated peptide ligands isolated from human leucocyte antigens
      (HLA) on the surface of native tumour tissue has so far not been successful.
      Using advanced mass spectrometry (MS) analysis, we survey the melanoma-associated
      immunopeptidome to a depth of 95,500 patient-presented peptides. We thereby
      discover a large spectrum of attractive target antigen candidates including
      cancer testis antigens and phosphopeptides. Most importantly, we identify peptide
      ligands presented on native tumour tissue samples harbouring somatic mutations.
      Four of eleven mutated ligands prove to be immunogenic by neoantigen-specific T
      cell responses. Moreover, tumour-reactive T cells with specificity for selected
      neoantigens identified by MS are detected in the patient's tumour and peripheral
      blood. We conclude that direct identification of mutated peptide ligands from
      primary tumour material by MS is possible and yields true neoepitopes with high
      relevance for immunotherapeutic strategies in cancer.

PMID- 27869122
TI  - CELF1 is a central node in post-transcriptional regulatory programmes underlying
      EMT.
AB  - The importance of translational regulation in tumour biology is increasingly
      appreciated. Here, we leverage polyribosomal profiling to prospectively define
      translational regulatory programs underlying epithelial-to-mesenchymal transition
      (EMT) in breast epithelial cells. We identify a group of ten translationally
      regulated drivers of EMT sharing a common GU-rich cis-element within the 3'
      untranslated region (3'-UTR) of their mRNA. These cis-elements, necessary for the
      regulatory activity imparted by these 3'-UTRs, are directly bound by the CELF1
      protein, which itself is regulated post-translationally during the EMT program.
      CELF1 is necessary and sufficient for both mesenchymal transition and metastatic
      colonization, and CELF1 protein, but not mRNA, is significantly overexpressed in
      human breast cancer tissues. Our data present an 11-component genetic pathway,
      invisible to transcriptional profiling approaches, in which the CELF1 protein
      functions as a central node controlling translational activation of genes driving
      EMT and ultimately tumour progression.

PMID- 27869124
TI  - Bisguanidinium dinuclear oxodiperoxomolybdosulfate ion pair-catalyzed
      enantioselective sulfoxidation.
AB  - Catalytic use of peroxomolybdate for asymmetric transformations has attracted
      increasing attention due to its catalytic properties and application in
      catalysis. Herein, we report chiral bisguanidinium dinuclear
      oxodiperoxomolybdosulfate [BG]2+[(MU-SO4)Mo2O2(MU-O2)2(O2)2]2- ion pair, as a
      catalyst for enantioselective sulfoxidation using aqueous H2O2 as the terminal
      oxidant. The ion pair catalyst is isolatable, stable and useful for the oxidation
      of a range of dialkyl sulfides. The practical utility was illustrated using a
      gram-scale synthesis of armodafinil, a commercial drug, with the catalyst
      generated in situ from 0.25 mol% of bisguanidinium and 2.5 mol% of Na2MoO4.2H2O.
      Structural characterization of this ion pair catalyst has been successfully
      achieved using single-crystal X-ray crystallography.

PMID- 27869125
TI  - Direct comparison of gluco-oligosaccharide oxidase variants and glucose oxidase:
      substrate range and H2O2 stability.
AB  - Glucose oxidase (GO) activity is generally restricted to glucose and is
      susceptible to inactivation by H2O2. By comparison, the Y300A variant of gluco
      oligosaccharide oxidase (GOOX) from Sarocladium strictum showed broader substrate
      range and higher H2O2 stability. Specifically, Y300A exhibited up to 40 times
      higher activity on all tested sugars except glucose, compared to GO. Moreover,
      fusion of the Y300A variant to a family 22 carbohydrate binding module from
      Clostridium thermocellum (CtCBM22A) nearly doubled its catalytic efficiency on
      glucose, while retaining significant activity on oligosaccharides. In the
      presence of 200 mM of H2O2, the recombinant CtCBM22A_Y300A retained 80% of
      activity on glucose and 100% of activity on cellobiose, the preferred substrate
      for this enzyme. By contrast, a commercial glucose oxidase reported to contain
      <=0.1 units catalase/ mg protein, retained 60% activity on glucose under the same
      conditions. GOOX variants appear to undergo a different mechanism of
      inactivation, as a loss of histidine instead of methionine was observed after
      H2O2 incubation. The addition of CtCBM22A also promoted functional binding of the
      fusion enzyme to xylan, facilitating its simultaneous purification and
      immobilization using edible oat spelt xylan, which might benefit the usage of
      this enzyme preparation in food and baking applications.

PMID- 27869123
TI  - A systems study reveals concurrent activation of AMPK and mTOR by amino acids.
AB  - Amino acids (aa) are not only building blocks for proteins, but also signalling
      molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a
      key mediator. However, little is known about whether aa, independently of mTORC1,
      activate other kinases of the mTOR signalling network. To delineate aa-stimulated
      mTOR network dynamics, we here combine a computational-experimental approach with
      text mining-enhanced quantitative proteomics. We report that AMP-activated
      protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2
      (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner.
      AMPK activation by aa is mediated by Ca2+/calmodulin-dependent protein kinase
      kinase beta (CaMKKbeta). In response, AMPK impinges on the autophagy regulators
      Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1
      antagonist that is activated by starvation. We find that aa acutely activate AMPK
      concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain
      autophagy. This may be required to maintain protein homoeostasis and deliver
      metabolite intermediates for biosynthetic processes.

PMID- 27869126
TI  - Caenorhabditis elegans as a model system to study post-translational
      modifications of human transthyretin.
AB  - The visceral protein transthyretin (TTR) is frequently affected by oxidative post
      translational protein modifications (PTPMs) in various diseases. Thus, better
      insight into structure-function relationships due to oxidative PTPMs of TTR
      should contribute to the understanding of pathophysiologic mechanisms. While the
      in vivo analysis of TTR in mammalian models is complex, time- and resource
      consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal
      model for the in vivo identification and characterization of drug-mediated
      oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization -
      time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that
      hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling
      the analysis of hTTR metabolism during the whole life-cycle. The suitability of
      the applied model was verified by exposing worms to D-penicillamine and
      menadione. Both drugs induced substantial changes in the oxidative PTPM pattern
      of hTTR. Additionally, for the first time a covalent binding of both drugs with
      hTTR was identified and verified by molecular modelling.

PMID- 27869128
TI  - Tuning the electrical conductance of metalloporphyrin supramolecular wires.
AB  - In contrast with conventional single-molecule junctions, in which the current
      flows parallel to the long axis or plane of a molecule, we investigate the
      transport properties of M(II)-5,15-diphenylporphyrin (M-DPP) single-molecule
      junctions (M=Co, Ni, Cu, or Zn divalent metal ions), in which the current flows
      perpendicular to the plane of the porphyrin. Novel STM-based conductance
      measurements combined with quantum transport calculations demonstrate that
      current-perpendicular-to-the-plane (CPP) junctions have three-orders-of-magnitude
      higher electrical conductances than their current-in-plane (CIP) counterparts,
      ranging from 2.10-2 G0 for Ni-DPP up to 8.10-2 G0 for Zn-DPP. The metal ion in
      the center of the DPP skeletons is strongly coordinated with the nitrogens of the
      pyridyl coated electrodes, with a binding energy that is sensitive to the choice
      of metal ion. We find that the binding energies of Zn-DPP and Co-DPP are
      significantly higher than those of Ni-DPP and Cu-DPP. Therefore when combined
      with its higher conductance, we identify Zn-DPP as the favoured candidate for
      high-conductance CPP single-molecule devices.

PMID- 27869127
TI  - Main Effects of Diagnoses, Brain Regions, and their Interaction Effects for
      Cerebral Metabolites in Bipolar and Unipolar Depressive Disorders.
AB  - Previous studies suggested patients with bipolar depressive disorder (BDd) or
      unipolar depressive disorder (UDd) have cerebral metabolites abnormalities. These
      abnormalities may stem from multiple sub-regions of gray matter in brain regions.
      Thirteen BDd patients, 20 UDd patients and 20 healthy controls (HC) were enrolled
      to investigate these abnormalities. Absolute concentrations of 5 cerebral
      metabolites (glutamate-glutamine (Glx), N-acetylaspartate (NAA), choline (Cho),
      myo-inositol (mI), creatine (Cr), parietal cortex (PC)) were measured from 4
      subregions (the medial frontal cortex (mPFC), anterior cingulate cortex (ACC),
      posterior cingulate cortex (PCC), and parietal cortex (PC)) of gray matter. Main
      and interaction effects of cerebral metabolites across subregions of gray matter
      were evaluated. For example, the Glx was significantly higher in BDd compared
      with UDd, and so on. As the interaction analyses showed, some interaction effects
      existed. The concentrations of BDds' Glx, Cho, Cr in the ACC and HCs' mI and Cr
      in the PC were higher than that of other interaction effects. In addition, the
      concentrations of BDds' Glx and Cr in the PC and HCs' mI in the ACC were
      statistically significant lower than that of other interaction effects. These
      findings point to region-related abnormalities of cerebral metabolites across
      subjects with BDd and UDd.

PMID- 27869130
TI  - Dynamic structure of active nematic shells.
AB  - When a thin film of active, nematic microtubules and kinesin motor clusters is
      confined on the surface of a vesicle, four +1/2 topological defects oscillate in
      a periodic manner between tetrahedral and planar arrangements. Here a theoretical
      description of nematics, coupled to the relevant hydrodynamic equations, is
      presented here to explain the dynamics of active nematic shells. In extensile
      microtubule systems, the defects repel each other due to elasticity, and their
      collective motion leads to closed trajectories along the edges of a cube. That
      motion is accompanied by oscillations of their velocities, and the emergence and
      annihilation of vortices. When the activity increases, the system enters a
      chaotic regime. In contrast, for contractile systems, which are representative of
      some bacterial suspensions, a hitherto unknown static structure is predicted,
      where pairs of defects attract each other and flows arise spontaneously.

PMID- 27869131
TI  - Optical computing for optical coherence tomography.
AB  - We propose an all-optical Fourier transformation system for real-time massive
      data processing in high speed optical coherence tomography (OCT). In the so
      called optical computing OCT, fast Fourier transformation (FFT) of A-scan signal
      is optically processed in real time before being detected by photoelectric
      detector. Therefore, the processing time for interpolation and FFT in traditional
      Fourier domain OCT can be dramatically eliminated. A processing rate of 10 mega-A
      scans/second was experimentally achieved, which is, to our knowledge, the highest
      speed for OCT imaging. Due to its fiber based all-optical configuration, this
      optical computing OCT system is ideal for ultrahigh speed volumetric OCT imaging
      in clinical application.

PMID- 27869129
TI  - Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid
      progenitors.
AB  - Recent efforts have attempted to convert non-blood cells into hematopoietic stem
      cells (HSCs) with the goal of generating blood lineages de novo. Here we show
      that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a
      developmentally distant lineage (fibroblasts) into 'induced hematopoietic
      progenitors' (iHPs). Functionally, iHPs generate acetylcholinesterase+
      megakaryocytes and phagocytic myeloid cells in vitro and can also engraft
      immunodeficient mice, generating myeloerythoid and B-lymphoid cells for up to 4
      months in vivo. Molecularly, iHPs transcriptionally resemble native Kit+
      hematopoietic progenitors. Mechanistically, reprogramming factor Lmo2 implements
      a hematopoietic programme in fibroblasts by rapidly binding to and upregulating
      the Hhex and Gfi1 genes within days. Moreover the reprogramming transcription
      factors also require extracellular BMP and MEK signalling to cooperatively
      effectuate reprogramming. Thus, the transcription factors that orchestrate
      embryonic hematopoiesis can artificially reconstitute this programme in
      developmentally distant fibroblasts, converting them into engraftable blood
      progenitors.

PMID- 27869132
TI  - Realisation of magnetically and atomically abrupt half-metal/semiconductor
      interface: Co2FeSi0.5Al0.5/Ge(111).
AB  - Halfmetal-semiconductor interfaces are crucial for hybrid spintronic devices.
      Atomically sharp interfaces with high spin polarisation are required for
      efficient spin injection. In this work we show that thin film of half-metallic
      full Heusler alloy Co2FeSi0.5Al0.5 with uniform thickness and B2 ordering can
      form structurally abrupt interface with Ge(111). Atomic resolution energy
      dispersive X-ray spectroscopy reveals that there is a small outdiffusion of Ge
      into specific atomic planes of the Co2FeSi0.5Al0.5 film, limited to a very narrow
      1 nm interface region. First-principles calculations show that this selective
      outdiffusion along the Fe-Si/Al atomic planes does not change the magnetic moment
      of the film up to the very interface. Polarized neutron reflectivity, x-ray
      reflectivity and aberration-corrected electron microscopy confirm that this
      interface is both magnetically and structurally abrupt. Finally, using first
      principles calculations we show that this experimentally realised interface
      structure, terminated by Co-Ge bonds, preserves the high spin polarization at the
      Co2FeSi0.5Al0.5/Ge interface, hence can be used as a model to study spin
      injection from half-metals into semiconductors.

PMID- 27869133
TI  - Demonstration of reconfigurable joint orbital angular momentum mode and space
      switching.
AB  - We propose and demonstrate space-selective switch functions employing orbital
      angular momentum (OAM) modes in the space domain for switching network. One is
      the switching among different OAM modes having different spatial phase
      structures, called OAM mode switching. The other is the switching among different
      space locations, called space switching. The switching operation mechanism relies
      on linear optics. Reconfigurable 4 * 4 OAM mode switching, space switching, and
      joint OAM mode and space switching fabric using a single spatial light modulator
      (SLM) are all demonstrated in the experiment. In addition, the presented OAM
      incorporated space-selective switch might be further extended to N * N joint OAM
      mode and space switching with fast response, scalability, cascading ability and
      compability to facilitate robust switching applications.

PMID- 27869134
TI  - Assessing SABU (Serum Anti Bisa Ular), the sole Indonesian antivenom: A proteomic
      analysis and neutralization efficacy study.
AB  - Serum Anti Ular Bisa (SABU) is the only snake antivenom produced locally in
      Indonesia; however, its effectiveness has not been rigorously evaluated. This
      study aimed to assess the protein composition and neutralization efficacy of
      SABU. SDS polyacrylamide gel electrophoresis, size-exclusion liquid
      chromatography and shotgun proteomics revealed that SABU consists of F(ab')2 but
      a significant amount of dimers, protein aggregates and contaminant albumins. SABU
      moderately neutralized Calloselasma rhodostoma venom (potency of 12.7 mg venom
      neutralized per ml antivenom, or 121.8 mg venom per g antivenom protein) and
      Bungarus fasciatus venom (0.9 mg/ml; 8.5 mg/g) but it was weak against the venoms
      of Naja sputatrix (0.3 mg/ml; 2.9 mg/g), Naja sumatrana (0.2 mg/ml; 1.8 mg/g) and
      Bungarus candidus (0.1 mg/ml; 1.0 mg/g). In comparison, NPAV, the Thai Neuro
      Polyvalent Antivenom, outperformed SABU with greater potencies against the venoms
      of N. sputatrix (0.6 mg/ml; 8.3 mg/g), N. sumatrana (0.5 mg/ml; 7.1 mg/g) and B.
      candidus (1.7 mg/ml; 23.2 mg/g). The inferior efficacy of SABU implies that a
      large antivenom dose is required clinically for effective treatment. Besides, the
      antivenom contains numerous impurities e.g., albumins that greatly increase the
      risk of hypersensitivity. Together, the findings indicate that the production of
      SABU warrants further improvement.

PMID- 27869135
TI  - Heat stroke internet searches can be a new heatwave health warning surveillance
      indicator.
AB  - The impact of major heatwave shocks on population morbidity and mortality has
      become an urgent public health concern. However, Current heatwave warning systems
      suffer from a lack of validation and an inability to provide accurate health risk
      warnings in a timely way. Here we conducted a correlation and linear regression
      analysis to test the relationship between heat stroke internet searches and heat
      stroke health outcomes in Shanghai, China, during the summer of 2013. We show
      that the resulting heatstroke index captures much of the variation in heat stroke
      cases and deaths. The correlation between heat stroke deaths, the search index
      and the incidence of heat stroke is higher than the correlation with maximum
      temperature. This study highlights a fast and effective heatwave health warning
      indicator with potential to be used throughout the world.

PMID- 27869136
TI  - Natural ageing process accelerates the release of Ag from functional textile in
      various exposure scenarios.
AB  - Natural ageing process occurs throughout the life cycle of textile products,
      which may possess influences on the release behavior of additives such as silver
      nanoparticles (Ag NPs). In this study, we assessed the releasability of Ag NPs
      from a Ag NPs functionalized textile in five different exposure scenarios (i.e.
      tap water (TW), pond water (PW), rain water (RW), artificial sweat (AS), and
      detergent solution (DS) along with deionized water (DW) as reference), which were
      very likely to occur throughout the life cycle of the textile. For the pristine
      textile, although the most remarkable release was found in DW (6-15 MUg Ag/g
      textile), the highest release rate was found in RW (around 7 MUg Ag/(g
      textile.h)). After ageing treatment, the total released Ag could be increased by
      75.7~386.0% in DW, AS and DS. Morphological analysis clearly showed that the Ag
      NPs were isolated from the surface of the textile fibre due to the ageing
      treatment. This study provides useful information for risk assessment of nano
      enhanced textile products.

PMID- 27869137
TI  - Anisotropic Strain Induced Directional Metallicity in Highly Epitaxial
      LaBaCo2O5.5+delta Thin Films on (110) NdGaO3.
AB  - Highly directional-dependent metal-insulator transition is observed in epitaxial
      double perovskite LaBaCo2O5.5+delta films. The film exhibit metallic along [100],
      but remain semiconducting along [010] under application of a magnetic field
      parallel to the surface of the film. The physical origin for the properties is
      identified as in-plane tensile strain arising from oxygen vacancies. First
      principle calculations suggested the tensile strain drastically alters the band
      gap, and the vanishing gap opens up [100] conduction channels for Fermi-surface
      electrons. Our observation of strain-induced highly directional-dependent metal
      insulator transition may open up new dimension for multifunctional devices.

PMID- 27869140
TI  - Corrigendum: Proteome mapping of Plasmodium: identification of the P. yoelii
      remodellome.

PMID- 27869138
TI  - The helminth product, ES-62 modulates dendritic cell responses by inducing the
      selective autophagolysosomal degradation of TLR-transducers, as exemplified by
      PKCdelta.
AB  - We have previously shown that ES-62, a phosphorylcholine (PC)-containing
      glycoprotein secreted by the parasitic filarial nematode Acanthocheilonema viteae
      targets dendritic cell (DC) responses, specifically by suppressing TLR4
      signalling to inhibit Th1/Th17-driven inflammation. We have now investigated the
      molecular mechanisms underpinning such immunomodulation and show here that ES-62
      mediated downregulation of protein kinase C-delta (PKC-delta), a TLR4-associated
      signalling mediator required for full activation of LPS-driven pro-inflammatory
      responses, is associated with induction of a low level of autophagic flux, as
      evidenced by upregulation and trafficking of p62 and LC3 and their consequent
      autophagolysosomal degradation. By contrast, the classical TLR4 ligand LPS,
      strongly upregulates p62 and LC3 expression but under such canonical TLR4
      signalling this upregulation appears to reflect a block in autophagic flux, with
      these elements predominantly degraded in a proteasomal manner. These data are
      consistent with autophagic flux acting to homeostatically suppress
      proinflammatory DC responses and indeed, blocking of PKC-delta degradation by the
      autophagolysosomal inhibitors, E64d plus pepstatin A, results in abrogation of
      the ES-62-mediated suppression of LPS-driven release of IL-6, IL-12p70 and TNF
      alpha by DCs. Thus, by harnessing this homeostatic regulatory mechanism, ES-62
      can protect against aberrant inflammation, either to promote parasite survival or
      serendipitously, exhibit therapeutic potential in inflammatory disease.

PMID- 27869142
TI  - Macroscopic superpositions and gravimetry with quantum magnetomechanics.
AB  - Precision measurements of gravity can provide tests of fundamental physics and
      are of broad practical interest for metrology. We propose a scheme for absolute
      gravimetry using a quantum magnetomechanical system consisting of a magnetically
      trapped superconducting resonator whose motion is controlled and measured by a
      nearby RF-SQUID or flux qubit. By driving the mechanical massive resonator to be
      in a macroscopic superposition of two different heights our we predict that our
      interferometry protocol could, subject to systematic errors, achieve a
      gravimetric sensitivity of Deltag/g ~ 2.2 * 10-10 Hz-1/2, with a spatial
      resolution of a few nanometres. This sensitivity and spatial resolution exceeds
      the precision of current state of the art atom-interferometric and corner-cube
      gravimeters by more than an order of magnitude, and unlike classical
      superconducting interferometers produces an absolute rather than relative
      measurement of gravity. In addition, our scheme takes measurements at ~10 kHz, a
      region where the ambient vibrational noise spectrum is heavily suppressed
      compared the ~10 Hz region relevant for current cold atom gravimeters.

PMID- 27869139
TI  - The transcription cofactor CRTC1 protects from aberrant hepatic lipid
      accumulation.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging global health
      problem. NAFLD encompasses a range of conditions associated with hepatic
      steatosis, aberrant accumulation of fat in hepatocytes. Although obesity and
      metabolic syndrome are considered to have a strong association with NAFLD,
      genetic factors that predispose liver to NAFLD and molecular mechanisms by which
      excess hepatic lipid develops remain largely unknown. We report that the
      transcription cofactor CRTC1 confers broad spectrum protection against hepatic
      steatosis development. CRTC1 directly interferes with the expression of genes
      regulated by lipogenic transcription factors, most prominently liver x receptor
      alpha (LXRalpha). Accordingly, Crtc1 deficient mice develop spontaneous hepatic
      steatosis in young age. As a cyclic AMP effector, CRTC1 mediates anti-steatotic
      effects of calorie restriction (CR). Notably, CRTC1 also mediates anti-lipogenic
      effects of bile acid signaling, whereas it is negatively regulated by miR-34a, a
      pathogenic microRNA upregulated in a broad spectrum of NAFLD. These patterns of
      gene function and regulation of CRTC1 are distinct from other CR-responsive
      proteins, highlighting critical protective roles that CRTC1 selectively plays
      against NAFLD development, which in turn provides novel opportunities for
      selectively targeting beneficial therapeutic effects of CR.

PMID- 27869141
TI  - Fronto-Striatal Glutamate in Autism Spectrum Disorder and Obsessive Compulsive
      Disorder.
AB  - Autism spectrum disorders (ASDs) and obsessive compulsive disorder (OCD) are
      often comorbid with the overlap based on compulsive behaviors. Although previous
      studies suggest glutamatergic deficits in fronto-striatal brain areas in both
      disorders, this is the first study to directly compare the glutamate
      concentrations across the two disorders with those in healthy control
      participants using both categorical and dimensional approaches. In the current
      multi-center study (four centers), we used proton magnetic resonance spectroscopy
      in 51 children with ASD, 29 with OCD, and 53 healthy controls (aged 8-13 years)
      to investigate glutamate (Glu) concentrations in two regions of the fronto
      striatal circuit: midline anterior cingulate cortex (ACC) and left dorsal
      striatum. Spectra were processed with Linear Combination Model. Group comparisons
      were performed with one-way analyses of variance including sex, medication use,
      and scanner site as covariates. In addition, a dimensional analysis was
      performed, linking glutamate with a continuous measure of compulsivity across
      disorders. There was a main group effect for ACC glutamate (p=0.019). Contrast
      analyses showed increased glutamate both in children with ASD and OCD compared
      with controls (p=0.007), but no differences between the two disorders (p=0.770).
      Dimensional analyses revealed a positive correlation between compulsive behavior
      (measured with the Repetitive Behavior Scale) and ACC glutamate (rho=0.24,
      p=0.03). These findings were robust across sites. No differences were found in
      the striatum. The current findings confirm overlap between ASD and OCD in terms
      of glutamate involvement. Glutamate concentration in ACC seems to be associated
      with the severity of compulsive behavior.

PMID- 27869144
TI  - Corrigendum: Efficient delivery of C/EBP beta gene into human mesenchymal stem
      cells via polyethylenimine-coated gold nanoparticles enhances adipogenic
      differentiation.

PMID- 27869145
TI  - Corrigendum: NPNT is Expressed by Osteoblasts and Mediates Angiogenesis via the
      Activation of Extracellular Signal-regulated Kinase.

PMID- 27869143
TI  - Genome mining unveils widespread natural product biosynthetic capacity in human
      oral microbe Streptococcus mutans.
AB  - Streptococcus mutans is a major pathogen causing human dental caries. As a Gram
      positive bacterium with a small genome (about 2 Mb) it is considered a poor
      source of natural products. Due to a recent explosion in genomic data available
      for S. mutans strains, we were motivated to explore the natural product
      production potential of this organism. Bioinformatic characterization of 169
      publically available genomes of S. mutans from human dental caries revealed a
      surprisingly rich source of natural product biosynthetic gene clusters. Anti
      SMASH analysis identified one nonribosomal peptide synthetase (NRPS) gene
      cluster, seven polyketide synthase (PKS) gene clusters and 136 hybrid PKS/NRPS
      gene clusters. In addition, 211 ribosomally synthesized and post-translationally
      modified peptides (RiPPs) clusters and 615 bacteriocin precursors were identified
      by a combined analysis using BAGEL and anti-SMASH. S. mutans harbors a rich and
      diverse natural product genetic capacity, which underscores the importance of
      probing the human microbiome and revisiting species that have traditionally been
      overlooked as "poor" sources of natural products.

PMID- 27869146
TI  - An ortholog of LEAFY in Jatropha curcas regulates flowering time and floral organ
      development.
AB  - Jatropha curcas seeds are an excellent biofuel feedstock, but seed yields of
      Jatropha are limited by its poor flowering and fruiting ability. Thus,
      identifying genes controlling flowering is critical for genetic improvement of
      seed yield. We isolated the JcLFY, a Jatropha ortholog of Arabidopsis thaliana
      LEAFY (LFY), and identified JcLFY function by overexpressing it in Arabidopsis
      and Jatropha. JcLFY is expressed in Jatropha inflorescence buds, flower buds, and
      carpels, with highest expression in the early developmental stage of flower buds.
      JcLFY overexpression induced early flowering, solitary flowers, and terminal
      flowers in Arabidopsis, and also rescued the delayed flowering phenotype of lfy
      15, a LFY loss-of-function Arabidopsis mutant. Microarray and qPCR analysis
      revealed several flower identity and flower organ development genes were
      upregulated in JcLFY-overexpressing Arabidopsis. JcLFY overexpression in Jatropha
      also induced early flowering. Significant changes in inflorescence structure,
      floral organs, and fruit shape occurred in JcLFY co-suppressed plants in which
      expression of several flower identity and floral organ development genes were
      changed. This suggests JcLFY is involved in regulating flower identity, floral
      organ patterns, and fruit shape, although JcLFY function in Jatropha floral
      meristem determination is not as strong as that of Arabidopsis.

PMID- 27869147
TI  - Interplay between VEGF and Nrf2 regulates angiogenesis due to intracranial venous
      hypertension.
AB  - Venous hypertension(VH) plays an important role in the pathogenesis of cerebral
      arteriovenous malformations (AVMs) and is closely associated with the HIF
      1alpha/VEGF signaling pathway. Nuclear factor erythroid 2-related factor 2(Nrf2)
      significantly influences angiogenesis; however, the interplay between Nrf2 and
      VEGF under VH in brain AVMs remains unclear. Therefore, our study aimed to
      investigate the interplay between Nrf2 and VEGF due to VH in brain AVMs.
      Immunohistochemistry indicated that Nrf2 and VEGF were highly expressed in human
      brain AVM tissues. In vivo, we established a VH model in both wild-type (WT) and
      siRNA-mediated Nrf2 knockdown rats. VH significantly increased the expression of
      Nrf2 and VEGF. Loss of Nrf2 markedly inhibited the upregulation of VEGF, as
      determined by Western blot analysis and qRT-PCR. In vitro, primary brain
      microvascular endothelial cells (BMECs) were isolated from WT and Nrf2-/- mice,
      and a VEGF-Nrf2 positive feed-back loop was observed in BMECs. By trans well
      assay and angiogenesis assay, Nrf2 knockout significantly inhibited the migration
      and vascular tube formation of BMECs. These findings suggest that the interplay
      between Nrf2 and VEGF can contribute to VH-induced angiogenesis in brain AVMs
      pathogenesis.

PMID- 27869148
TI  - Motor noise is rich signal in autism research and pharmacological treatments.
AB  - The human body is in constant motion, from every breath that we take, to every
      visibly purposeful action that we perform. Remaining completely still on command
      is a major achievement as involuntary fluctuations in our motions are difficult
      to keep under control. Here we examine the noise-to-signal ratio of micro
      movements present in time-series of head motions extracted from resting-state
      functional magnetic resonance imaging scans in 1048 participants. These included
      individuals with autism spectrum disorders (ASD) and healthy-controls in shared
      data from the Autism Brain Imaging Data Exchange (ABIDE) and the Attention
      Deficit Hyperactivity Disorder (ADHD-200) databases. We find excess noise and
      randomness in the ASD cases, suggesting an uncertain motor-feedback signal. A
      power-law emerged describing an orderly relation between the dispersion and shape
      of the probability distribution functions best describing the stochastic
      properties under consideration with respect to intelligence quotient (IQ-scores).
      In ASD, deleterious patterns of noise are consistently exacerbated with the
      presence of secondary (comorbid) neuropsychiatric diagnoses, lower verbal and
      performance intelligence, and autism severity. Importantly, such patterns in ASD
      are present whether or not the participant takes psychotropic medication. These
      data unambiguously establish specific noise-to-signal levels of head micro
      movements as a biologically informed core feature of ASD.

PMID- 27869149
TI  - Multiple Resource Use Efficiency (mRUE): A New Concept for Ecosystem Production.
AB  - The resource-driven concept, which is an important school for investigating
      ecosystem production, has been applied for decades. However, the regulatory
      mechanisms of production by multiple resources remain unclear. We formulated a
      new algorithm model that integrates multiple resource uses to study ecosystem
      production and tested its applications on a water-availability gradient in semi
      arid grassland. The result of our experiment showed that changes in water
      availability significantly affected the resources of light and nitrogen, and
      altered the relationships among multiple resource absorption rate (epsilon),
      multiple resource use efficiency (mRUE), and available resource (Ravail). The
      increased water availability suppressed ecosystem mRUE (i.e., "declining marginal
      returns"); The changes in mRUE had a negative effect on epsilon (i.e., "inverse
      feedback"). These two processes jointly regulated that the stimulated single
      resource availability would promote ecosystem production rather than suppress it,
      even when mRUE was reduced. This study illustrated the use of the mRUE model in
      exploring the coherent relationships among the key parameters on regulating the
      ecosystem production for future modeling, and evaluated the sensitivity of this
      conceptual model under different dataset properties. However, this model needs
      extensive validation by the ecological community before it can extrapolate this
      method to other ecosystems in the future.

PMID- 27869153
TI  - Cell Senescence: Controlling the senescence-associated secretory phenotype.

PMID- 27869150
TI  - Skin-on-a-chip model simulating inflammation, edema and drug-based treatment.
AB  - Recent advances in microfluidic cell cultures enable the construction of in vitro
      human skin models that can be used for drug toxicity testing, disease study.
      However, current in vitro skin model have limitations to emulate real human skin
      due to the simplicity of model. In this paper, we describe the development of
      'skin-on-a-chip' to mimic the structures and functional responses of the human
      skin. The proposed model consists of 3 layers, on which epidermal, dermal and
      endothelial components originated from human, were cultured. The microfluidic
      device was designed for co-culture of human skin cells and each layer was
      separated by using porous membranes to allow interlayer communication. Skin
      inflammation and edema were induced by applying tumor necrosis factor alpha on
      dermal layer to demonstrate the functionality of the system. The expression
      levels of proinflammatory cytokines were analyzed to illustrate the feasibility.
      In addition, we evaluated the efficacy of therapeutic drug testing model using
      our skin chip. The function of skin barrier was evaluated by staining tight
      junctions and measuring a permeability of endothelium. Our results suggest that
      the skin-on-a-chip model can potentially be used for constructing in vitro skin
      disease models or for testing the toxicity of cosmetics or drugs.

PMID- 27869154
TI  - Nuclear organization: NUP-tial binding to super-enhancers.

PMID- 27869155
TI  - 3D solutions to complex gene regulation.

PMID- 27869156
TI  - Stem cells: Coordinated expansion of cells in the skin.

PMID- 27869152
TI  - Reversible strain control of magnetic anisotropy in magnetoelectric
      heterostructures at room temperature.
AB  - The ability to tune both magnetic and electric properties in magnetoelectric (ME)
      composite heterostructures is crucial for multiple transduction applications
      including energy harvesting or magnetic field sensing, or other transduction
      devices. While large ME coupling achieved through interfacial strain-induced
      rotation of magnetic anisotropy in magnetostrictive/piezoelectric multiferroic
      heterostructures has been demonstrated, there are presently certain restrictions
      for achieving a full control of magnetism in an extensive operational dynamic
      range, limiting practical realization of this effect. Here, we demonstrate the
      possibility of generating substantial reversible anisotropy changes through
      induced interfacial strains driven by applied electric fields in magnetostrictive
      thin films deposited on (0 1 1)-oriented domain-engineered ternary relaxor
      ferroelectric single crystals with extended temperature and voltage ranges as
      compared to binary relaxors. We show, through a combination of angular
      magnetization and magneto-optical domain imaging measurements, that a 90 degrees 
      in-plane rotation of the magnetic anisotropy and propagation of magnetic domains
      with low applied electric fields under zero electric field bias are realized. To
      our knowledge, the present value attained for converse magnetoelectric coupling
      coefficient is the highest achieved in the linear piezoelectric regime and
      expected to be stable for a wide temperature range, thus representing a step
      towards practical ME transduction devices.

PMID- 27869157
TI  - DNA Repair: RNA-DNA hybrids: a double-edged sword in genomic stability.

PMID- 27869151
TI  - The lectin-like protein 1 in Lactobacillus rhamnosus GR-1 mediates tissue
      specific adherence to vaginal epithelium and inhibits urogenital pathogens.
AB  - The probiotic Lactobacillus rhamnosus GR-1 has been documented to survive
      implantation onto the vaginal epithelium and interfere with urogenital pathogens.
      However, the molecular mechanisms involved are largely unknown. Here, we report
      for the first time the construction of dedicated knock-out mutants in L.
      rhamnosus GR-1 to enable the study of gene functions. In a search for genes
      responsible for the adherence capacity of L. rhamnosus GR-1, a genomic region
      encoding a protein with homology to lectin-like proteins was identified.
      Phenotypic analyses of the knock-out mutant of L. rhamnosus GR-1 revealed a two
      fold decreased adhesion to the vaginal and ectocervical epithelial cell lines
      compared to wild-type. In contrast, the adhesion to gastro-intestinal epithelial
      (Caco2) and endocervical cell lines (Hela and End1/E6E7) was not drastically
      affected by the mutation, suggesting that the LGR-1_Llp1 lectins mediates tissue
      tropism. The purified LGR-1_Llp1 protein also inhibited biofilm formation and
      adhesion of uropathogenic Escherichia coli. For the first time, an important role
      for a novel lectin-like protein in the adhesion capacity and host cell-specific
      interaction of a vaginal probiotic Lactobacillus strain has been discovered, with
      an additional role in pathogen inhibition.

PMID- 27869158
TI  - Mapping the 3D genome: Aiming for consilience.
AB  - The spatial organization of genomes is studied using microscopy- and chromosome
      conformation capture (3C)-based methods. The two types of methods produce data
      that are often consistent, but there are cases where they appear discordant.
      These cases provide opportunities to derive better models of chromatin folding,
      which can reconcile the datasets.

PMID- 27869159
TI  - Fundamental Scaling Laws in Nanophotonics.
AB  - The success of information technology has clearly demonstrated that
      miniaturization often leads to unprecedented performance, and unanticipated
      applications. This hypothesis of "smaller-is-better" has motivated optical
      engineers to build various nanophotonic devices, although an understanding
      leading to fundamental scaling behavior for this new class of devices is missing.
      Here we analyze scaling laws for optoelectronic devices operating at micro and
      nanometer length-scale. We show that optoelectronic device performance scales non
      monotonically with device length due to the various device tradeoffs, and analyze
      how both optical and electrical constrains influence device power consumption and
      operating speed. Specifically, we investigate the direct influence of scaling on
      the performance of four classes of photonic devices, namely laser sources,
      electro-optic modulators, photodetectors, and all-optical switches based on three
      types of optical resonators; microring, Fabry-Perot cavity, and plasmonic metal
      nanoparticle. Results show that while microrings and Fabry-Perot cavities can
      outperform plasmonic cavities at larger length-scales, they stop working when the
      device length drops below 100 nanometers, due to insufficient functionality such
      as feedback (laser), index-modulation (modulator), absorption (detector) or field
      density (optical switch). Our results provide a detailed understanding of the
      limits of nanophotonics, towards establishing an opto-electronics roadmap, akin
      to the International Technology Roadmap for Semiconductors.

PMID- 27869160
TI  - Pot1 OB-fold mutations unleash telomere instability to initiate tumorigenesis.
AB  - Chromosomal aberrations are a hallmark of human cancers, with complex cytogenetic
      rearrangements leading to genetic changes permissive for cancer initiation and
      progression. Protection of Telomere 1 (POT1) is an essential component of the
      shelterin complex and functions to maintain chromosome stability by repressing
      the activation of aberrant DNA damage and repair responses at telomeres. Sporadic
      and familial mutations in the oligosaccharide-oligonucleotide (OB) folds of POT1
      have been identified in many human cancers, but the mechanism underlying how
      hPOT1 mutations initiate tumorigenesis has remained unclear. Here we show that
      the human POT1's OB-folds are essential for the protection of newly replicated
      telomeres. Oncogenic mutations in hPOT1 OB-fold fail to bind to single-stranded
      telomeric DNA, eliciting a DNA damage response at telomeres that promote
      inappropriate chromosome fusions via the mutagenic alternative non-homologous end
      joining (A-NHEJ) pathway. hPOT1 mutations also result in telomere elongation and
      the formation of transplantable hematopoietic malignancies. Strikingly,
      conditional deletion of both mPot1a and p53 in mouse mammary epithelium resulted
      in development of highly invasive breast carcinomas and the formation of whole
      chromosomes containing massive arrays of telomeric fusions indicative of multiple
      breakage-fusion-bridge cycles. Our results reveal that hPOT1 OB-folds are
      required to protect and prevent newly replicated telomeres from engaging in A
      NHEJ mediated fusions that would otherwise promote genome instability to fuel
      tumorigenesis.

PMID- 27869161
TI  - Therapeutic targeting of necroptosis by Smac mimetic bypasses apoptosis
      resistance in acute myeloid leukemia cells.
AB  - Resistance to apoptosis, for example due to overexpression of Inhibitor of
      Apoptosis (IAP) proteins, is associated with poor prognosis in acute myeloid
      leukemia (AML). Here, we identify that Smac mimetics such as BV6, which
      antagonizes IAP proteins, elicit necroptosis in AML cells, in which apoptosis is
      inhibited pharmacologically by caspase inhibitors or genetically by caspase-8
      knockdown. Importantly, BV6 triggers necroptosis also in apoptosis-resistant
      patient-derived AML blasts, underlining the clinical relevance of our findings.
      Mechanistically, we show that BV6-induced cell death depends on key components of
      necroptosis signaling such as RIP1, RIP3 and MLKL, since pharmacological or
      genetic inhibition of these proteins significantly protects AML cells from BV6
      mediated cell death, whereas PGAM5 is dispensable. Interestingly, we identify
      constitutive tumor necrosis factor-alpha (TNFalpha) secretion and an
      autocrine/paracrine TNFalpha loop as critical mediators of BV6-induced
      necroptosis in AML cell lines and patient-derived blasts, as the TNFalpha
      blocking antibody Enbrel or tumor necrosis factor-alpha receptor 1 (TNFR1)
      knockdown significantly rescue cell death. Notably, AML cells exhibit high basal
      levels of TNFalpha compared to non-malignant CD34+ cells, which is further
      increased by BV6. In conclusion, this is the first report showing that Smac
      mimetics circumvent apoptosis resistance in AML cells by inducing necroptosis in
      a TNFalpha-dependent manner, which has important implications for the development
      of new strategies to overcome treatment resistance in AML.

PMID- 27869162
TI  - The histone demethylase KDM4B regulates peritoneal seeding of ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) has poor prognosis and rapid recurrence because
      of widespread dissemination of peritoneal metastases at diagnosis. Multiple
      pathways contribute to the aggressiveness of ovarian cancer, including hypoxic
      signaling mechanisms. In this study, we have determined that the hypoxia
      inducible histone demethylase KDM4B is expressed in ~60% of EOC tumors assayed,
      including primary and matched metastatic tumors. Expression of KDM4B in tumors is
      positively correlated with expression of the tumor hypoxia marker CA-IX, and is
      robustly induced in EOC cell lines exposed to hypoxia. KDM4B regulates expression
      of metastatic genes and pathways, and loss of KDM4B increases H3K9 trimethylation
      at the promoters of target genes like LOXL2, LCN2 and PDGFB. Suppressing KDM4B
      inhibits ovarian cancer cell invasion, migration and spheroid formation in vitro.
      KDM4B also regulates seeding and growth of peritoneal tumors in vivo, where its
      expression corresponds to hypoxic regions. This is the first demonstration that a
      Jumonji-domain histone demethylase regulates cellular processes required for
      peritoneal dissemination of cancer cells, one of the predominant factors
      affecting prognosis of EOC. The pathways regulated by KDM4B may present novel
      opportunities to develop combinatorial therapies to improve existing therapies
      for EOC patients.

PMID- 27869163
TI  - Wwox-Brca1 interaction: role in DNA repair pathway choice.
AB  - In this study, loss of expression of the fragile site-encoded Wwox protein was
      found to contribute to radiation and cisplatin resistance of cells, responses
      that could be associated with cancer recurrence and poor outcome. WWOX gene
      deletions occur in a variety of human cancer types, and reduced Wwox protein
      expression can be detected early during cancer development. We found that Wwox
      loss is followed by mild chromosome instability in genomes of mouse embryo
      fibroblast cells from Wwox-knockout mice. Human and mouse cells deficient for
      Wwox also exhibit significantly enhanced survival of ionizing radiation and
      bleomycin treatment, agents that induce double-strand breaks (DSBs). Cancer cells
      that survive radiation recur more rapidly in a xenograft model of irradiated
      breast cancer cells; Wwox-deficient cells exhibited significantly shorter tumor
      latencies vs Wwox-expressing cells. This Wwox effect has important consequences
      in human disease: in a cohort of cancer patients treated with radiation, Wwox
      deficiency significantly correlated with shorter overall survival times. In
      examining mechanisms underlying Wwox-dependent survival differences, we found
      that Wwox-deficient cells exhibit enhanced homology directed repair (HDR) and
      decreased non-homologous end-joining (NHEJ) repair, suggesting that Wwox
      contributes to DNA DSB repair pathway choice. Upon silencing of Rad51, a protein
      critical for HDR, Wwox-deficient cells were resensitized to radiation. We also
      demonstrated interaction of Wwox with Brca1, a driver of HDR, and show via
      immunofluorescent detection of repair proteins at ionizing radiation-induced DNA
      damage foci that Wwox expression suppresses DSB repair at the end-resection step
      of HDR. We propose a genome caretaker function for WWOX, in which Brca1-Wwox
      interaction supports NHEJ as the dominant DSB repair pathway in Wwox-sufficient
      cells. Taken together, the experimental results suggest that reduced Wwox
      expression, a common occurrence in cancers, dysregulates DSB repair, enhancing
      efficiency of likely mutagenic repair, and enabling radiation and cisplatin
      treatment resistance.

PMID- 27869164
TI  - The hot-spot p53R172H mutant promotes formation of giant spermatogonia triggered
      by DNA damage.
AB  - Overexpression of mutant p53 is a common finding in most cancers but testicular
      tumours accumulate wild-type p53 (wtp53). In contrast to the accepted concept
      that p53 homozygous mutant mice do not accumulate mutant p53 in normal cells, our
      study on a mutant p53 mouse model of Li-Fraumeni syndrome harbouring the hot-spot
      p53R172H mutation described an elevated level of mutant p53 in non-cancerous
      mouse tissues. Here we use detailed immunohistochemical analysis to document the
      expression of p53R172H in mouse testis. In developing and adult testes, p53R172H
      was expressed in gonocytes, type A, Int, B spermatogonia as well as in pre
      Sertoli cells and Leydig cells but was undetectable in spermatocytes and
      spermatids. A similar staining pattern was demonstrated for wtp53. However, the
      intensity of wtp53 staining was generally weaker than that of p53R172H, which
      indicates that the expression of p53R172H can be a surrogate marker of p53 gene
      transcription. Comparing the responses of wtp53 and p53R172H to irradiation, we
      found persistent DNA double-strand breaks in p53R172H testes and the formation of
      giant spermatogonia (GSG) following persistent DNA damage in p53R172H and p53
      null mice. Strikingly, we found that p53R172H promotes spontaneous formation of
      GSG in non-stressed p53R172H ageing mice. Two types of GSG: Viable and
      Degenerative GSG were defined. We elucidate the factors involved in the formation
      of GSG: the loss of p53 function is a requirement for the formation of GSG
      whereas DNA damage acts as a promoting trigger. The formation of GSG does not
      translate to higher efficacy of testicular tumorigenesis arising from mutant p53
      cells, which might be due to the presence of delayed-onset of p53-independent
      apoptosis.

PMID- 27869165
TI  - TAp63 suppresses mammary tumorigenesis through regulation of the Hippo pathway.
AB  - Mechanisms regulating the transition of mammary epithelial cells (MECs) to
      mammary stem cells (MaSCs) and to tumor-initiating cells (TICs) have not been
      entirely elucidated. The p53 family member, p63, is critical for mammary gland
      development and contains transactivation domain isoforms, which have tumor
      suppressive activities, and the DeltaN isoforms, which act as oncogenes. In the
      clinic, p63 is often used as a diagnostic marker, and further analysis of the
      function of TAp63 in the mammary gland is critical for improved diagnosis and
      patient care. Loss of TAp63 in mice leads to the formation of aggressive
      metastatic mammary adenocarcinoma at 9-16 months of age. Here we show that TAp63
      is crucial for the transition of mammary cancer cells to TICs. When TAp63 is
      lost, MECs express embryonic and MaSC signatures and activate the Hippo pathway.
      These data indicate a crucial role for TAp63 in mammary TICs and provide a
      mechanism for its role as a tumor- and metastasis-suppressor in breast cancer.

PMID- 27869166
TI  - SKP2 loss destabilizes EZH2 by promoting TRAF6-mediated ubiquitination to
      suppress prostate cancer.
AB  - EZH2 is crucial for the progression of prostate cancer (PCa) and castration
      resistant prostate cancer (CRPC) through upregulation and activation of
      progenitor genes, as well as androgen receptor (AR)-target genes. However, the
      mechanisms by which EZH2 is regulated in PCa and CRPC remain elusive. Here we
      report that EZH2 is post-transcriptionally regulated by SKP2 in vitro in cultured
      cells and in vivo in mouse models. We observed aberrant upregulation of Skp2,
      Ezh2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse
      embryonic fibroblasts (MEFs) and Pten null mouse prostate tissues. Loss of Skp2
      resulted in a striking decrease of Ezh2 levels in Pten/Trp53 double-null MEFs and
      in prostate tumors of Pten/Trp53 double-null mutant mice. SKP2 knockdown
      decreased EZH2 levels in human PCa cells through upregulation of TRAF6-mediated
      and lysine(K) 63-linked ubiquitination of EZH2 for degradation. Ectopic
      expression of TRAF6 promoted the K63-linked ubiquitination of EZH2 to decrease
      EZH2 and H3K27me3 levels in PCa cells. In contrast, TRAF6 knockdown resulted in a
      reduced EZH2 ubiquitination with an increase of EZH2 and H3K27me3 levels in PCa
      cells. Furthermore, the catalytically dead mutant TRAF6 C70A abolished the TRAF6
      mediated polyubiquitination of recombinant human EZH2 in vitro. Most importantly,
      a concurrent elevation of Skp2 and Ezh2 was found in CRPC tumors of Pten/Trp53
      mutant mice, and expression levels of SKP2 and EZH2 were positively correlated in
      human PCa specimens. Taken together, our findings revealed a novel mechanism on
      EZH2 ubiquitination and an important signaling network of SKP2-TRAF6
      EZH2/H3K27me3, and targeting SKP2-EZH2 pathway may be a promising therapeutic
      strategy for CRPC treatment.

PMID- 27869167
TI  - Cystine addiction of triple-negative breast cancer associated with EMT augmented
      death signaling.
AB  - Despite the advances in the diagnosis and treatment of breast cancer, breast
      cancers still cause significant mortality. For some patients, especially those
      with triple-negative breast cancer, current treatments continue to be limited and
      ineffective. Therefore, there remains an unmet need for a novel therapeutic
      approach. One potential strategy is to target the altered metabolic state that is
      rewired by oncogenic transformation. Specifically, this rewiring may render
      certain outside nutrients indispensable. To identify such a nutrient, we
      performed a nutrigenetic screen by removing individual amino acids to identify
      possible addictions across a panel of breast cancer cells. This screen revealed
      that cystine deprivation triggered rapid programmed necrosis, but not apoptosis,
      in the basal-type breast cancer cells mostly seen in TNBC tumors. In contrast,
      luminal-type breast cancer cells are cystine-independent and exhibit little death
      during cystine deprivation. The cystine addiction phenotype is associated with a
      higher level of cystine-deprivation signatures noted in the basal type breast
      cancer cells and tumors. We found that the cystine-addicted breast cancer cells
      and tumors have strong activation of TNFalpha and MEKK4-p38-Noxa pathways that
      render them susceptible to cystine deprivation-induced necrosis. Consistent with
      this model, silencing of TNFalpha and MEKK4 dramatically reduces cystine-deprived
      death. In addition, the cystine addiction phenotype can be abrogated in the
      cystine-addictive cells by miR-200c, which converts the mesenchymal-like cells to
      adopt epithelial features. Conversely, the introduction of inducers of epithelial
      mesenchymal transition (EMT) in cystine-independent breast cancer cells conferred
      the cystine-addiction phenotype by modulating the signaling components of cystine
      addiction. Together, our data reveal that cystine-addiction is associated with
      EMT in breast cancer during tumor progression. These findings provide the genetic
      and mechanistic basis to explain how cystine deprivation triggers necrosis by
      activating pre-existing oncogenic pathways in cystine-addicted TNBC with
      prominent mesenchymal features.

PMID- 27869169
TI  - Critical role of the POT1 OB domain in maintaining genomic stability.
AB  - Oligonucleotide/oligosaccharide-binding (OB) domain-containing proteins have been
      identified as critical for telomere maintenance, DNA repair, transcription and
      other DNA metabolism processes. Protection of telomere 1 (POT1), a telomere
      binding protein, has an OB domain like single-strand binding protein (SSB1). In
      this issue of Oncogene, Gu et al. present evidence that POT1, like SSB1, is
      required to maintain genomic stability. This work, in conjunction with results
      from previous investigators, highlights the importance of POT1 in telomere
      metabolism. Inactivation of POT1 telomere protective functions in mouse models
      lacking p53 expression in the breast epithelium unleashes a torrent of DNA damage
      responses (DDRs) at the telomeres, culminating in karyotypic alterations with
      massive arrays of telomere fusions. Therefore, POT1 is not only required to
      promote telomere homeostasis, but also plays an essential role in maintaining a
      stable genome.

PMID- 27869168
TI  - miR-127 promotes EMT and stem-like traits in lung cancer through a feed-forward
      regulatory loop.
AB  - The coordination between cellular differentiation and the mesenchymal/stem
      transition is essential for both embryo development and neoplasia, suggesting a
      mechanistic link between these two major processes. In this work we show that miR
      127, an embryo-expressing lung miRNA, was prominently induced in lung
      adenocarcinoma and correlated with poor prognosis. Elevated miR-127 level drove a
      pronounced shift from the epithelial to the mesenchymal phenotype in cancer
      cells, and this shift was associated with their acquisition of stem-like traits,
      increased resistance to the epidermal growth factor receptor inhibitor and tumor
      propagating potential. In contrast, antagonizing miR-127 markedly reversed this
      malignant transition, compromised the stem-like properties and the in vivo
      tumorigenic capability of cancer cells. Importantly, a regulatory loop involving
      the inflammatory signals NF-kappaB, miR-127 and tumor necrosis factor alpha
      induced protein 3 was uncovered as a self-reinforcing circuitry that ensured an
      aggressive transition in lung cancer. Thus, this work identifies a novel
      molecular mechanism linking stemness, malignancy and inflammation, opening a new
      avenue for cancer treatment.

PMID- 27869170
TI  - Androgen receptor promotes melanoma metastasis via altering the miRNA-539
      3p/USP13/MITF/AXL signals.
AB  - Early studies demonstrated that male melanoma patients have worse survival than
      female patients, yet the detailed mechanisms for this gender difference remain
      unclear. We analyzed around 100 cases of human melanoma and found that androgen
      receptor (AR) positive melanoma patients have worse survival outcomes compared
      with AR-negative melanoma patients. Here we report that AR can have positive
      roles to increase melanoma cell invasion in multiple cell lines in vitro and a
      mouse model in vivo. Mechanism dissection suggest that AR increases melanoma cell
      invasion via modulating the MITF-AXL signals via altering the miRNA-539-3p/USP13
      signaling to increase MITF protein degradation through a reduction of de
      ubiquitination. Restoring MITF can reverse AR-enhanced melanoma cell invasion.
      Together, our results demonstrate that AR can promote melanoma metastasis via
      altering the miRNA-539-3p/USP13/MITF/AXL signal and targeting this newly
      identified signal with AR degradation enhancer ASC-J9 may help us to better
      suppress the melanoma metastasis.

PMID- 27869171
TI  - Epigenetic activation of the prostaglandin receptor EP4 promotes resistance to
      endocrine therapy for breast cancer.
AB  - Approximately 75% of breast cancers express estrogen receptor alpha (ERalpha) and
      depend on estrogen signals for continued growth. Aromatase inhibitors (AIs)
      prevent estrogen production and inhibit ER signaling, resulting in decreased
      cancer recurrence and mortality. Advanced tumors treated with AIs almost always
      develop resistance to these drugs via the upregulation of alternative growth
      signals. The mechanisms that drive this resistance-especially epigenetic events
      that alter gene expression-are, however, not well understood. Genome-wide DNA
      methylation and expression analysis of cell line models of acquired AI resistance
      indicated that prostaglandin E2 receptor 4 (PTGER4) is upregulated after
      demethylation in resistant cells. Knockdown and inhibitor studies demonstrate
      that PTGER4 is essential for estrogen-independent growth. Our exploratory
      analysis of downstream signaling indicates that PTGER4 likely promotes AI
      resistance via ligand-independent activation of the ERalpha-cofactor CARM1. We
      believe that we have discovered a novel epigenetic mechanism for altering cell
      signaling and acquiring endocrine therapy resistance. Our findings indicate that
      PTGER4 is a potential drug target in AI-resistant cancers. In addition, the
      epigenetic component of PTGER4 regulation suggests that further study of PTGER4
      may yield valuable insights into how DNA methylation-targeted diagnoses and
      treatments can improve AI-resistant breast cancer treatment.

PMID- 27869172
TI  - A redox state-dictated signalling pathway deciphers the malignant cell
      specificity of CD40-mediated apoptosis.
AB  - CD40, a member of the tumour necrosis factor receptor (TNFR) superfamily, has the
      capacity to cause extensive apoptosis in carcinoma cells, while sparing normal
      epithelial cells. Yet, apoptosis is only achieved by membrane-presented CD40
      ligand (mCD40L), as soluble receptor agonists are but weakly pro-apoptotic. Here,
      for the first time we have identified the precise signalling cascade underpinning
      mCD40L-mediated death as involving sequential TRAF3 stabilisation, ASK1
      phosphorylation, MKK4 (but not MKK7) activation and JNK/AP-1 induction, leading
      to a Bak- and Bax-dependent mitochondrial apoptosis pathway. TRAF3 is central in
      the activation of the NADPH oxidase (Nox)-2 component p40phox and the elevation
      of reactive oxygen species (ROS) is essential in apoptosis. Strikingly, CD40
      activation resulted in down-regulation of Thioredoxin (Trx)-1 to permit ASK1
      activation and apoptosis. Although soluble receptor agonist alone could not
      induce death, combinatorial treatment incorporating soluble CD40 agonist and
      pharmacological inhibition of Trx-1 was functionally equivalent to the signal
      triggered by mCD40L. Finally, we demonstrate using normal, 'para-malignant' and
      tumour-derived cells that progression to malignant transformation is associated
      with increase in oxidative stress in epithelial cells, which coincides with
      increased susceptibility to CD40 killing, while in normal cells CD40 signalling
      is cytoprotective. Our studies have revealed the molecular nature of the tumour
      specificity of CD40 signalling and explained the differences in pro-apoptotic
      potential between soluble and membrane-bound CD40 agonists. Equally importantly,
      by exploiting a unique epithelial culture system that allowed us to monitor
      alterations in the redox-state of epithelial cells at different stages of
      malignant transformation, our study reveals how pro-apoptotic signals can elevate
      ROS past a previously hypothesised 'lethal pro-apoptotic threshold' to induce
      death; an observation that is both of fundamental importance and carries
      implications for cancer therapy.

PMID- 27869173
TI  - Pterostilbene induces apoptosis and cell cycle arrest in diffuse large B-cell
      lymphoma cells.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin
      lymphoma (NHL). Pterostilbene, a natural dimethylated analog of resveratrol, has
      been shown to possess diverse pharmacological activities, including anti
      inflammatory, antioxidant and anticancer properties. However, to the best of our
      knowledge, there has been no study of the effects of pterostilbene upon
      hematological malignancies. Herein, we report the antitumor activity and
      mechanism of pterostilbene against DLBCL cells both in vitro and in vivo. We
      found that pterostilbene treatment resulted in a dose-dependent inhibition of
      cell viability. In addition, pterostilbene exhibited a strong cytotoxic effect,
      as evidenced not only by reductions of mitochondrial membrane potential (MMP) but
      also by increases in cellular apoptotic index and reactive oxygen species (ROS)
      levels, leading to arrest in the S-phase of the cell cycle. Furthermore,
      pterostilbene treatment directly up-regulated p-p38MAPK and down-regulated p
      ERK1/2. In vivo, intravenous administration of pterostilbene inhibited tumor
      development in xenograft mouse models. Overall, the results suggested that
      pterostilbene is a potential anti-cancer pharmaceutical against human DLBCL by a
      mechanism involving the suppression of ERK1/2 and activation of p38MAPK signaling
      pathways.

PMID- 27869174
TI  - Developmental Reprogramming in Mesenchymal Stromal Cells of Human Subjects with
      Idiopathic Pulmonary Fibrosis.
AB  - Cellular plasticity and de-differentiation are hallmarks of tissue/organ
      regenerative capacity in diverse species. Despite a more restricted capacity for
      regeneration, humans with age-related chronic diseases, such as cancer and
      fibrosis, show evidence of a recapitulation of developmental gene programs. We
      have previously identified a resident population of mesenchymal stromal cells
      (MSCs) in the terminal airways-alveoli by bronchoalveolar lavage (BAL) of human
      adult lungs. In this study, we characterized MSCs from BAL of patients with
      stable and progressive idiopathic pulmonary fibrosis (IPF), defined as <5% and
      >=10% decline, respectively, in forced vital capacity over the preceding 6-month
      period. Gene expression profiles of MSCs from IPF subjects with progressive
      disease were enriched for genes regulating lung development. Most notably, genes
      regulating early tissue patterning and branching morphogenesis were
      differentially regulated. Network interactive modeling of a set of these genes
      indicated central roles for TGF-beta and SHH signaling. Importantly, fibroblast
      growth factor-10 (FGF-10) was markedly suppressed in IPF subjects with
      progressive disease, and both TGF-beta1 and SHH signaling were identified as
      critical mediators of this effect in MSCs. These findings support the concept of
      developmental gene re-activation in IPF, and FGF-10 deficiency as a potentially
      critical factor in disease progression.

PMID- 27869176
TI  - Quantitative secretomic analysis of pancreatic cancer cells in serum-containing
      conditioned medium.
AB  - Pancreatic cancer is a highly metastatic and chemo-resistant disease. Secreted
      proteins involved in cell-cell interactions play an important role in changing
      the tumor microenvironment. Previous studies generally focus on the secretome of
      cancer cell line from serum-free media, due to the serious interference of fetal
      bovine serum (FBS). However, serum-starvation may alter expression patterns of
      secreted proteins. Hence, efforts to decrease the interference of serum in
      proteomic analysis of serum-containing media have been hampered to quantitatively
      measure the tumor secretion levels. Recently, the metabolic labeling, protein
      equalization, protein fractionation and filter-aided sample preparation (FASP)
      strategy (MLEFF) has been successfully used to avoid the disturbance of serum on
      secretome analysis. Here, this efficient method was applied for comparative
      secretome analysis of two hamster pancreatic cancer cells with differentially
      metastatic potentials, enabling the observation of 161 differentially expressed
      proteins, including 106 proteins that had been previously reported and detected
      in plasma. By integrated analysis of our data and publicly available
      bioinformatics resources, we found that a combination panel consisting of CDH3,
      PLAU, and LFNG might improve the prognosis of overall pancreatic cancer survival.
      These secreted proteins may serve as a potential therapeutic targets for
      pancreatic cancer metastasis.

PMID- 27869177
TI  - Repressor logic modules assembled by rolling circle amplification platform to
      construct a set of logic gates.
AB  - Small molecule metabolites and their allosterically regulated repressors play an
      important role in many gene expression and metabolic disorder processes. These
      natural sensors, though valuable as good logic switches, have rarely been
      employed without transcription machinery in cells. Here, two pairs of repressors,
      which function in opposite ways, were cloned, purified and used to control DNA
      replication in rolling circle amplification (RCA) in vitro. By using metabolites
      and repressors as inputs, RCA signals as outputs, four basic logic modules were
      constructed successfully. To achieve various logic computations based on these
      basic modules, we designed series and parallel strategies of circular templates,
      which can further assemble these repressor modules in an RCA platform to realize
      twelve two-input Boolean logic gates and a three-input logic gate. The RCA-output
      and RCA-assembled platform was proved to be easy and flexible for complex logic
      processes and might have application potential in molecular computing and
      synthetic biology.

PMID- 27869175
TI  - An antibacterial and absorbable silk-based fixation material with impressive
      mechanical properties and biocompatibility.
AB  - Implant-associated infections and non-absorbing materials are two important
      reasons for a second surgical procedure to remove internal fixation devices after
      an orthopedic internal fixation surgery. The objective of this study was to
      produce an antibacterial and absorbable fixation screw by adding gentamicin to
      silk-based materials. The antibacterial activity was assessed against
      Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro by
      plate cultivation and scanning electron microscopy (SEM). We also investigated
      the properties, such as the mechanical features, swelling properties,
      biocompatibility and degradation, of gentamicin-loaded silk-based screws (GSS) in
      vitro. The GSS showed significant bactericidal effects against S. aureus and E.
      coli. The antibacterial activity remained high even after 4 weeks of immersion in
      protease solution. In addition, the GSS maintained the remarkable mechanical
      properties and excellent biocompatibility of pure silk-based screws (PSS).
      Interestingly, after gentamicin incorporation, the degradation rate and water
      absorbing capacity increased and decreased, respectively. These GSS provide both
      impressive material properties and antibacterial activity and have great
      potential for use in orthopedic implants to reduce the incidence of second
      surgeries.

PMID- 27869178
TI  - Importance of the C-terminal histidine residues of Helicobacter pylori GroES for
      Toll-like receptor 4 binding and interleukin-8 cytokine production.
AB  - Helicobacter pylori infection is associated with the development of gastric and
      duodenal ulcers as well as gastric cancer. GroES of H. pylori (HpGroES) was
      previously identified as a gastric cancer-associated virulence factor. Our group
      showed that HpGroES induces interleukin-8 (IL-8) cytokine release via a Toll-like
      receptor 4 (TLR4)-dependent mechanism and domain B of the protein is crucial for
      interactions with TLR4. In the present study, we investigated the importance of
      the histidine residues in domain B. To this end, a series of point mutants were
      expressed in Escherichia coli, and the corresponding proteins purified.
      Interestingly, H96, H104 and H115 were not essential, whereas H100, H102, H108,
      H113 and H118 were crucial for IL-8 production and TLR4 interactions in KATO-III
      cells. These residues were involved in nickel binding. Four of five residues,
      H102, H108, H113 and H118 induced certain conformation changes in extended domain
      B structure, which is essential for interactions with TLR4 and consequent IL-8
      production. We conclude that interactions of nickel ions with histidine residues
      in domain B help to maintain the conformation of the C-terminal region to
      conserve the integrity of the HpGroES structure and modulate IL-8 release.

PMID- 27869179
TI  - Interleukins 17 and 23 in patients with gastric neoplasms.
AB  - Recently there has been heightened interest in the potential significance of
      interleukin (IL)-17 and IL-23 in the development/progression of human
      malignancies. Here, we analyzed the systemic levels of these cytokines in 75
      patients with different types of gastric neoplasms (carcinoma, gastrointestinal
      stromal tumors, neuroendocrine neoplasms, and lymphomas) and 42 healthy
      volunteers. We found that patients with all types of gastric neoplasms have
      significantly lower IL-23 levels. However, in comparison to the levels in healthy
      individuals, IL-17 concentrations were lower only in patients with types of
      gastric neoplasms other than carcinoma. Interestingly, IL-17 levels significantly
      differed between patients with early and advanced gastric carcinoma. No
      significant associations were detected between the systemic levels of examined
      interleukins and TNM staging. However, peripheral levels of IL-23 were correlated
      with the absolute numbers of circulating populations of bone marrow-derived
      mesenchymal and very small embryonic/epiblast-like stem cells in patients with
      gastric carcinoma. ROC curve analyses demonstrated that systemic levels of IL-17
      seem to meet basic criteria for consideration as a helpful diagnostic marker in
      the detection of gastric carcinoma. In conclusion, our study provides
      translational evidence confirming the clinical significance of IL-17 and IL-23 in
      the pathogenesis of different types of gastric neoplasms in humans.

PMID- 27869180
TI  - Silver Nanoparticles Impact Biofilm Communities and Mussel Settlement.
AB  - Silver nanoparticles (AgNPs) demonstrating good antimicrobial activity are widely
      used in many fields. However, the impact of AgNPs on the community structures of
      marine biofilms that drive biogeochemical cycling processes and the recruitment
      of marine invertebrate larvae remains unknown. Here, we employed MiSeq sequencing
      technology to evaluate the bacterial communities of 28-day-old marine biofilms
      formed on glass, polydimethylsiloxane (PDMS), and PDMS filled with AgNPs and
      subsequently tested the influence of these marine biofilms on plantigrade
      settlement by the mussel Mytilus coruscus. AgNP-filled PDMS significantly reduced
      the dry weight and bacterial density of biofilms compared with the glass and PDMS
      controls. AgNP incorporation impacted bacterial communities by reducing the
      relative abundance of Flavobacteriaceae (phylum: Bacteroidetes) and increasing
      the relative abundance of Vibrionaceae (phylum: Proteobacteria) in 28-day-old
      biofilms compared to PDMS. The settlement rate of M. coruscus on 28-day-old
      biofilms developed on AgNPs was lower by >30% compared to settlement on control
      biofilms. Thus, the incorporation of AgNPs influences biofilm bacterial
      communities in the marine environment and subsequently inhibits mussel
      settlement.

PMID- 27869181
TI  - Functional states of rat cortical circuits during the unpredictable availability
      of a reward-related cue.
AB  - Proper performance of acquired abilities can be disturbed by the unexpected
      occurrence of external changes. Rats trained with an operant conditioning task
      (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1)
      schedule were subsequently placed in a Skinner box in which the lever could be
      removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked
      in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1
      medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC
      basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT
      situations. While lever presses were accompanied by a significant increase in
      fPSP slopes at the five synapses, the unpredictable absence of the lever were
      accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral
      analysis of local field potentials (LFPs) recorded when the animal approached the
      corresponding area in the lever OUT situation presented lower spectral powers
      than during lever IN occasions for all recording sites, apart from CA1. Thus, the
      unpredictable availability of a reward-related cue modified the activity of
      cortical and subcortical areas related with the acquisition of operant learning
      tasks, suggesting an immediate functional reorganization of these neural circuits
      to address the changed situation and to modify ongoing behaviors accordingly.

PMID- 27869182
TI  - The effects of non-self-sustained oscillators on the en-trainment ability of the
      suprachiasmatic nucleus.
AB  - In mammals, the circadian rhythms of behavioral and physiological activities are
      regulated by an endogenous clock located in the suprachiasmatic nucleus (SCN).
      The SCN is composed of ~20,000 neurons, of which some are capable of self
      sustained oscillations, while the others do not oscillate in a self-sustainable
      manner, but show arrhythmic patterns or damped oscillations. Thus far, the
      effects of these non-self-sustained oscillatory neurons are not fully explored.
      Here, we examined how the proportion of the non-self-sustained oscillators
      affects the free running period under constant darkness and the ability to
      entrain to the light-dark cycle. We find that the proportion does not affect the
      free running period, but plays a significant role in the range of entrainment. We
      also find that its effect on the entrainment range depends on the region where
      the non-self-sustained oscillators are located. If the non-self-sustained
      oscillatory neurons are situated in the light-sensitive subregion, the
      entrainment range narrows when the proportion increases. If they are situated in
      the light-insensitive subregion, however, the entrainment range broadens with the
      increase of the proportion. We suggest that the heterogeneity within the light
      sensitive and light-insensitive subregions of the SCN has important consequences
      for how the clock works.

PMID- 27869183
TI  - Anion-controlled dimer distance induced unique solid-state fluorescence of cyano
      substituted styrene pyridinium.
AB  - Molecular packing arrangements play a key role in dominating the photophysical
      properties of luminophores in aggregated state but fine control of the molecular
      packing is a great challenge. This article describes a unique cyano substituted
      styrene pyridinium with interesting solid-state fluorescence that can be finely
      tuned by simple change of counteranions. The dilute solutions of the organic
      salts (PyCl, PyNO3, PyOTs and PyPh4B) exhibit very weak fluorescence. The
      crystals of the organic salts (PyCl, PyNO3, and PyOTs) show much enhanced
      fluorescence compared with their dilute solutions. It is interesting that the
      emissions changed from bluish-green to deep-blue and fluorescence quantum yields
      increase from 2.5% to 13.1% with the increasing of steric hindrance of the anions
      from chloridion, nitrate, to p-toluenesulfonate. Crystal and DFT studies reveal
      that the enhanced fluorescence is ascribed to the formation of dimers and bigger
      anions induce larger molecular separation in dimers. Tetraphenylboron anion with
      very large steric hindrance impedes the formation of dimers and thus results in
      non-fluorescent salt (PyPh4B). Meanwhile, this unique dimeric packing endows the
      crystal of PyNO3 with anisotropic fluorescence.

PMID- 27869184
TI  - In-situ growth of MnO2 crystals under nanopore-constraint in carbon nanofibers
      and their electrochemical performance.
AB  - Growing MnO2 nanocrystals in the bulk of porous carbon nanofibers is conducted in
      a KMnO4 aqueous solution aimed to enhance the electrochemical performance of
      MnO2. The rate of redox reaction between KMnO4 and carbon was controlled by the
      concentration of KMnO4 in a neutral solution. The MnO2 nanoparticles grow along
      with (211) crystal faces when the redox reaction happens on the surface of fibers
      under 1D constraint, while the nanoparticles grow along with (200) crystal faces
      when the redox reaction happens in the bulk of fibers under 3D constraint. The
      composite, where MnO2 nanoparticles are formed in the bulk under a constraint,
      yields an electrode material for supercapacitors showing good electron transport,
      rapid ion penetration, fast and reversible Faradaic reaction, and excellent rate
      performance. The capacitance of the composite electrode could be 1282 F g-1 under
      a current density of 0.2 A g-1 in 1 M Na2SO4 electrolyte. A symmetric
      supercapacitor delivers energy density of 36 Wh kg-1 with power density of 39 W
      kg-1, and can maintain 7.5 Wh kg-1 at 10.3 kW kg-1. It exhibits an excellent
      electrochemical cycling stability with 101% initial capacitance and 95% columbic
      efficiency even after 1000 cycles of charge/discharge.

PMID- 27869185
TI  - Metal artifact reduction through MVCBCT and kVCT in radiotherapy.
AB  - This study proposes a new method for removal of metal artifacts from megavoltage
      cone beam computed tomography (MVCBCT) and kilovoltage CT (kVCT) images. Both
      images were combined to obtain prior image, which was forward projected to obtain
      surrogate data and replace metal trace in the uncorrected kVCT image. The
      corrected image was then reconstructed through filtered back projection. A
      similar radiotherapy plan was designed using the theoretical CT image, the
      uncorrected kVCT image, and the corrected image. The corrected images removed
      most metal artifacts, and the CT values were accurate. The corrected image also
      distinguished the hollow circular hole at the center of the metal. The
      uncorrected kVCT image did not display the internal structure of the metal, and
      the hole was misclassified as metal portion. Dose distribution calculated based
      on the corrected image was similar to that based on the theoretical CT image. The
      calculated dose distribution also evidently differed between the uncorrected kVCT
      image and the theoretical CT image. The use of the combined kVCT and MVCBCT to
      obtain the prior image can distinctly improve the quality of CT images containing
      large metal implants.

PMID- 27869186
TI  - Regulation of Anticancer Styrylpyrone Biosynthesis in the Medicinal Mushroom
      Inonotus obliquus Requires Thioredoxin Mediated Transnitrosylation of S
      nitrosoglutathione Reductase.
AB  - The medicinal macrofungus Inonotus obliquus widely utilized as folk medicine in
      Russia and Baltic countries is a source of phenylpropanoid-derived styrylpyrone
      polyphenols that can inhibit tumor proliferation. Insights into the regulatory
      machinery that controls I. obliquus styrylpyrone polyphenol biosynthesis will
      enable strategies to increase the production of these molecules. Here we show
      that Thioredoxin (Trx) mediated transnitrosylation of S-nitrosoglutathione
      reductase (GSNOR) underpins the regulation of styrylpyrone production, driven by
      nitric oxide (NO) synthesis triggered by P. morii coculture. NO accumulation
      results in the S-nitrosylation of PAL and 4CL required for the synthesis of
      precursor phenylpropanoids and styrylpyrone synthase (SPS), integral to the
      production of styrylpyrone, inhibiting their activities. These enzymes are
      targeted for denitrosylation by Trx proteins, which restore their activity.
      Further, this Trx S-nitrosothiol (SNO) reductase activity was potentiated
      following S-nitrosylation of Trx proteins at a non-catalytic cysteine (Cys)
      residue. Intriguingly, this process was counterbalanced by Trx denitrosylation,
      mediated by Trx-dependent transnitrosylation of GSNOR. Thus, unprecedented
      interplay between Trx and GSNOR oxidoreductases regulates the biosynthesis of
      styrylpyrone polyphenols in I. obliquus.

PMID- 27869187
TI  - A new species of Trichoderma hypoxylon harbours abundant secondary metabolites.
AB  - Some species of Trichoderma are fungicolous on fungi and have been extensively
      studied and commercialized as biocontrol agents. Multigene analyses coupled with
      morphology, resulted in the discovery of T. hypoxylon sp. nov., which was
      isolated from surface of the stroma of Hypoxylon anthochroum. The new taxon
      produces Trichoderma- to Verticillium-like conidiophores and hyaline conidia.
      Phylogenetic analyses based on combined ITS, TEF1-alpha and RPB2 sequence data
      indicated that T. hypoxylon is a well-distinguished species with strong bootstrap
      support in the polysporum group. Chemical assessment of this species reveals a
      richness of secondary metabolites with trichothecenes and
      epipolythiodiketopiperazines as the major compounds. The fungicolous life style
      of T. hypoxylon and the production of abundant metabolites are indicative of the
      important ecological roles of this species in nature.

PMID- 27869189
TI  - Species-Specific Standard Redox Potential of Thiol-Disulfide Systems: A Key
      Parameter to Develop Agents against Oxidative Stress.
AB  - Microscopic standard redox potential, a new physico-chemical parameter was
      introduced and determined to quantify thiol-disulfide equilibria of biological
      significance. The highly composite, codependent acid-base and redox equilibria of
      thiols could so far be converted into pH-dependent, apparent redox potentials (E'
      degrees ) only. Since the formation of stable metal-thiolate complexes precludes
      the direct thiol-disulfide redox potential measurements by usual electrochemical
      techniques, an indirect method had to be elaborated. In this work, the species
      specific, pH-independent standard redox potentials of glutathione were determined
      primarily by comparing it to 1-methylnicotinamide, the simplest NAD+ analogue.
      Secondarily, the species-specific standard redox potentials of the two-electron
      redox transitions of cysteamine, cysteine, homocysteine, penicillamine, and
      ovothiol were determined using their microscopic redox equilibrium constants with
      glutathione. The 30 different, microscopic standard redox potential values show
      close correlation with the respective thiolate basicities and provide sound means
      for the development of potent agents against oxidative stress.

PMID- 27869191
TI  - Solar Output Controls Periodicity in Lake Productivity and Wetness at
      Southernmost South America.
AB  - Cyclic changes in total solar irradiance (TSI) during the Holocene are known to
      affect global climatic conditions and cause cyclic climatic oscillations, e.g.,
      Bond events and related changes of environmental conditions. However, the
      processes how changes in TSI affect climate and environment of the Southern
      Hemisphere, especially in southernmost South America, a key area for the global
      climate, are still poorly resolved. Here we show that highly sensitive proxies
      for aquatic productivity derived from sediments of a lake near the Chilean South
      Atlantic coast (53  degrees S) strongly match the cyclic changes in TSI
      throughout the Holocene. Intra-lake productivity variations show a periodicity of
      ~200-240 years coherent with the time series of TSI-controlled cosmogenic nuclide
      10Be production. In addition TSI dependent periodicity of Bond events (~1500
      years) appear to control wetness at the LH site indicated by mineral matter
      erosion from the catchment to the lake assumingly through shifts of the position
      of the southern westerly wind belt. Thus, both intra-lake productivity and
      wetness at the southernmost South America are directly or indirectly controlled
      by TSI.

PMID- 27869190
TI  - Embodied neurofeedback with an anthropomorphic robotic hand.
AB  - Neurofeedback-guided motor imagery training (NF-MIT) has been suggested as a
      promising therapy for stroke-induced motor impairment. Whereas much NF-MIT
      research has aimed at signal processing optimization, the type of sensory
      feedback given to the participant has received less attention. Often the feedback
      signal is highly abstract and not inherently coupled to the mental act performed.
      In this study, we asked whether an embodied feedback signal is more efficient for
      neurofeedback operation than a non-embodiable feedback signal. Inspired by the
      rubber hand illusion, demonstrating that an artificial hand can be incorporated
      into one's own body scheme, we used an anthropomorphic robotic hand to visually
      guide the participants' motor imagery act and to deliver neurofeedback. Using two
      experimental manipulations, we investigated how a participant's neurofeedback
      performance and subjective experience were influenced by the embodiability of the
      robotic hand, and by the neurofeedback signal's validity. As pertains to
      embodiment, we found a promoting effect of robotic-hand embodiment in subjective,
      behavioral, electrophysiological and electrodermal measures. Regarding
      neurofeedback signal validity, we found some differences between real and sham
      neurofeedback in terms of subjective and electrodermal measures, but not in terms
      of behavioral and electrophysiological measures. This study motivates the further
      development of embodied feedback signals for NF-MIT.

PMID- 27869188
TI  - Structural and immunomodulatory differences among lactobacilli exopolysaccharides
      isolated from intestines of mice with experimentally induced inflammatory bowel
      disease.
AB  - Characteristic changes in the microbiota biostructure and a decreased tolerance
      to intestinal bacteria have been associated with inflammatory bowel disease
      (IBD). However, few studies have examined the constituents of the intestinal
      microbiota, including the surface molecules of the bacteria, in healthy and IBD
      subsets. Here, we compare the chemical structures and immunomodulatory properties
      of the exopolysaccharides (EPS) of lactobacilli isolated from mice with induced
      IBD (IBD "+") versus those of healthy mice (IBD "-"). Classical structural
      analyses were performed using nuclear magnetic resonance spectroscopy and mass
      spectrometry. Immunomodulatory properties were assessed by stimulation of
      dendritic cells derived from mouse bone marrow or human peripheral mononuclear
      blood cells. Our results revealed that EPS produced by IBD "+" species are
      structurally different from those isolated from IBD "-". Moreover, the
      structurally different EPS generate different immune responses by dendritic
      cells. We speculate that resident strains could, upon gut inflammation, switch to
      producing EPS with specific motifs that are absent from lactobacilli IBD "-",
      and/or that bacteria with a particular EPS structure might inhabit the inflamed
      intestinal mucosa. This study may shed light on the role of EPS in IBD and help
      the development of a specific probiotic therapy for this disease.

PMID- 27869193
TI  - Towards 'smart lasers': self-optimisation of an ultrafast pulse source using a
      genetic algorithm.
AB  - Short-pulse fibre lasers are a complex dynamical system possessing a broad space
      of operating states that can be accessed through control of cavity parameters.
      Determination of target regimes is a multi-parameter global optimisation problem.
      Here, we report the implementation of a genetic algorithm to intelligently locate
      optimum parameters for stable single-pulse mode- locking in a Figure-8 fibre
      laser, and fully automate the system turn-on procedure. Stable ultrashort pulses
      are repeatably achieved by employing a compound fitness function that monitors
      both temporal and spectral output properties of the laser. Our method of encoding
      photonics expertise into an algorithm and applying machine-learning principles
      paves the way to self-optimising 'smart' optical technologies.

PMID- 27869194
TI  - A highly efficient, stable, durable, and recyclable filter fabricated by
      femtosecond laser drilling of a titanium foil for oil-water separation.
AB  - It has been a long standing challenge to efficiently separate oil and water since
      prehistoric times, and now it has become even more desirable in oily wastewater
      purification and oil spill cleanup. Here we introduce a super oil-water
      separation filter with superhydrophilicity and underwater superoleophobicity,
      fabricated using femtosecond laser micro-hole drilling of a titanium foil. Such a
      simply-made filter, without any modification, can achieve a separation efficiency
      exceeding 99% in eight typical oil-water mixtures. It remains highly efficient
      after 40 cycles of recycling and after suffering erosion by corrosive media.
      Furthermore, the used filter, polluted with oil, could be recovered by
      ultraviolet illumination. The flux of filtered water is tunable by simply
      selecting the aperture of the microhole or the spacing between adjacent
      microholes. Such advanced functionality is due to roughness and the TiO2 layers
      on the ablated surface during fabrication. With superhydrophilic and
      superoleophobic surfaces, this oil-water filer is also suitable for applications
      in anti-fouling, anti-smudge, anti-fog, and self-cleaning.

PMID- 27869192
TI  - Peritoneal adhesion prevention with a biodegradable and injectable N,O
      carboxymethyl chitosan-aldehyde hyaluronic acid hydrogel in a rat repeated-injury
      model.
AB  - Postoperative peritoneal adhesion is one of the serious issues because it induces
      severe clinical disorders. In this study, we prepared biodegradable and
      injectable hydrogel composed of N,O-carboxymethyl chitosan (NOCC) and aldehyde
      hyaluronic acid (AHA), and assessed its anti-adhesion effect in a rigorous and
      severe recurrent adhesion model which is closer to clinical conditions. The
      flexible hydrogel, which gelated in 66 seconds at 37  degrees C, was cross-linked
      by the schiff base derived from the amino groups of NOCC and aldehyde groups in
      AHA. In vitro cytotoxicity test showed the hydrogel was non-toxic. In vitro and
      in vivo degradation examinations demonstrated the biodegradable and
      biocompatibility properties of the hydrogel. The hydrogel discs could prevent the
      invasion of fibroblasts, whereas fibroblasts encapsulated in the porous 3
      dimensional hydrogels could grow and proliferate well. Furthermore, the hydrogel
      was applied to evaluate the anti-adhesion efficacy in a more rigorous recurrent
      adhesion model. Compared with normal saline group and commercial hyaluronic acid
      (HA) hydrogel, the NOCC-AHA hydrogel exhibited significant reduction of
      peritoneal adhesion. Compared to control group, the blood and abdominal lavage
      level of tPA was increased in NOCC-AHA hydrogel group. These findings suggested
      that NOCC-AHA hydrogel had a great potential to serve as an anti-adhesion
      candidate.

PMID- 27869195
TI  - Quantum memory with strong and controllable Rydberg-level interactions.
AB  - Realization of distributed quantum systems requires fast generation and long-term
      storage of quantum states. Ground atomic states enable memories with storage
      times in the range of a minute, however their relatively weak interactions do not
      allow fast creation of non-classical collective states. Rydberg atomic systems
      feature fast preparation of singly excited collective states and their efficient
      mapping into light, but storage times in these approaches have not yet exceeded a
      few microseconds. Here we demonstrate a system that combines fast quantum state
      generation and long-term storage. An initially prepared coherent state of an
      atomic memory is transformed into a non-classical collective atomic state by
      Rydberg-level interactions in less than a microsecond. By sheltering the quantum
      state in the ground atomic levels, the storage time is increased by almost two
      orders of magnitude. This advance opens a door to a number of quantum protocols
      for scalable generation and distribution of entanglement.

PMID- 27869197
TI  - Polarization bandgaps and fluid-like elasticity in fully solid elastic
      metamaterials.
AB  - Elastic waves exhibit rich polarization characteristics absent in acoustic and
      electromagnetic waves. By designing a solid elastic metamaterial based on three
      dimensional anisotropic locally resonant units, here we experimentally
      demonstrate polarization bandgaps together with exotic properties such as 'fluid
      like' elasticity. We construct elastic rods with unusual vibrational properties,
      which we denote as 'meta-rods'. By measuring the vibrational responses under
      flexural, longitudinal and torsional excitations, we find that each vibration
      mode can be selectively suppressed. In particular, we observe in a finite
      frequency regime that all flexural vibrations are forbidden, whereas longitudinal
      vibration is allowed-a unique property of fluids. In another case, the torsional
      vibration can be suppressed significantly. The experimental results are well
      interpreted by band structure analysis, as well as effective media with
      indefinite mass density and negative moment of inertia. Our work opens an
      approach to efficiently separate and control elastic waves of different
      polarizations in fully solid structures.

PMID- 27869196
TI  - T-cell stimuli independently sum to regulate an inherited clonal division fate.
AB  - In the presence of antigen and costimulation, T cells undergo a characteristic
      response of expansion, cessation and contraction. Previous studies have revealed
      that population-level reproducibility is a consequence of multiple clones
      exhibiting considerable disparity in burst size, highlighting the requirement for
      single-cell information in understanding T-cell fate regulation. Here we show
      that individual T-cell clones resulting from controlled stimulation in vitro are
      strongly lineage imprinted with highly correlated expansion fates. Progeny from
      clonal families cease dividing in the same or adjacent generations, with inter
      clonal variation producing burst-size diversity. The effects of costimulatory
      signals on individual clones sum together with stochastic independence;
      therefore, the net effect across multiple clones produces consistent, but
      heterogeneous population responses. These data demonstrate that substantial
      clonal heterogeneity arises through differences in experience of clonal
      progenitors, either through stochastic antigen interaction or by differences in
      initial receptor sensitivities.

PMID- 27869198
TI  - Sub-optimality in motor planning is retained throughout 9 days practice of 2250
      trials.
AB  - Optimality in motor planning, as well as accuracy in motor execution, is required
      to maximize expected gain under risk. In this study, we tested whether humans are
      able to update their motor planning. Participants performed a coincident timing
      task with an asymmetric gain function, in which optimal response timing to gain
      the highest total score depends on response variability. Their behaviours were
      then compared using a Bayesian optimal decision model. After 9 days of practicing
      2250 trials, the total score increased, and temporal variance decreased. On the
      other hand, the participants showed consistent risk-seeking or risk-averse
      behaviour, preserving suboptimal motor planning. These results suggest that a
      human's computational ability to calculate an optimal motor plan is limited, and
      it is difficult to improve it through repeated practice with a score feedback.

PMID- 27869199
TI  - Ion mobility spectrometry as a simple and rapid method to measure the plasma
      propofol concentrations for intravenous anaesthesia monitoring.
AB  - The plasma propofol concentration is important information for anaesthetists to
      monitor and adjust the anaesthesia depth for patients during a surgery operation.
      In this paper, a stand-alone ion mobility spectrometer (IMS) was constructed for
      the rapid measurement of the plasma propofol concentrations. Without any sample
      pre-treatment, the plasma samples were dropped on a piece of glass microfiber
      paper and then introduced into the IMS cell by the thermal desorption directly.
      Each individual measurement could be accomplished within 1 min. For the plasma
      propofol concentrations from 1 to 12 MUg mL-1, the IMS response was linear with a
      correlation coefficient R2 of 0.998, while the limit of detection was evaluated
      to be 0.1 MUg mL-1. These measurement results did meet the clinical application
      requirements. Furthermore, other clinically-often-used drugs, including
      remifentanil, flurbiprofen and atracurium, were found no significant interference
      with the qualitative and quantitative analysis of the plasma propofol. The plasma
      propofol concentrations measured by IMS were correlated well with those measured
      by the high performance liquid chromatography (HPLC). The results confirmed an
      excellent agreement between these two methods. Finally, this method was applied
      to monitor the plasma propofol concentrations for a patient undergoing surgery,
      demonstrating its capability of anaesthesia monitoring in real clinical
      environments.

PMID- 27869200
TI  - Classification of Tandem Mass Spectra for Identification of N- and O-linked
      Glycopeptides.
AB  - Analysis of intact glycopeptides by mass spectrometry is essential to determining
      the microheterogeneity of protein glycosylation. Higher-energy collisional
      dissociation (HCD) fragmentation of glycopeptides generates mono- or disaccharide
      ions called oxonium ions that carry information about the structure of the
      fragmented glycans. Here, we investigated the link between glycan structures and
      the intensity of oxonium ions in the spectra of glycopeptides and utilized this
      information to improve the identification of glycopeptides in biological samples.
      Tandem spectra of glycopeptides from fetuin, glycophorin A, ovalbumin and gp120
      tryptic digests were used to build a spectral database of N- and O-linked
      glycopeptides. Logistic regression was applied to this database to develop model
      to distinguish between the spectra of N- and O-linked glycopeptides. Remarkably,
      the developed model was found to reliably distinguish between the N- and O-linked
      glycopeptides using the spectral features of the oxonium ions using verification
      spectral set. Finally, the performance of the developed predictive model was
      evaluated in HILIC enriched glycopeptides extracted from human serum. The results
      showed that pre-classification of tandem spectra based on their glycosylation
      type improved the identification of N-linked glycopeptides. The developed model
      facilitates interpretation of tandem mass spectrometry data for assignment of
      glycopeptides.

PMID- 27869201
TI  - Cardioprotection by combination of three compounds from ShengMai preparations in
      mice with myocardial ischemia/reperfusion injury through AMPK activation-mediated
      mitochondrial fission.
AB  - GRS is a drug combination of three active components including ginsenoside Rb1,
      ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai
      preparations, a widely used traditional Chinese medicine for the treatment of
      cardiovascular diseases in clinic. The present study explores the
      cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury
      compared with ShengMai preparations and investigates the underlying mechanisms.
      GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy
      as Shengmai preparations, as evidenced by decreased myocardium infarct size,
      ameliorated histological features, the decrease of LDH production and improved
      cardiac function, and also produced a significant decrease of apoptotic index.
      Mechanistically, GRS alleviated myocardial apoptosis by inhibiting the
      mitochondrial mediated apoptosis pathway as reflected by inhibition of caspase-3
      activity, normalization of Bcl-2/Bax levels and improved mitochondrial function.
      Moreover, GRS prevented cardiomyocytes mitochondrial fission and upregulated
      AMPKalpha phosphorylation. Interestingly, AMPK activation prevented hypoxia and
      reoxygenation induced mitochondrial fission in cardiomyocytes and GRS actions
      were significantly attenuated by knockdown of AMPKalpha. Collectively, these data
      show that GRS is effective in mitigating MI/R injury by suppressing mitochondrial
      mediated apoptosis and modulating AMPK activation-mediated mitochondrial fission,
      thereby providing a rationale for future clinical applications and potential
      therapeutic strategy for MI/R injury.

PMID- 27869203
TI  - No effect of natural transformation on the evolution of resistance to
      bacteriophages in the Acinetobacter baylyi model system.
AB  - The adaptive benefits of natural transformation, the active uptake of free DNA
      molecules from the environment followed by incorporation of this DNA into the
      genome, may be the improved response to selection resulting from increased
      genetic variation. Drawing analogies with sexual reproduction, transformation may
      be particularly beneficial when selection rapidly fluctuates during coevolution
      with virulent parasites ('the Red Queen Hypothesis'). Here we test this
      hypothesis by experimentally evolving the naturally transformable and
      recombinogenic species Acinetobacter baylyi with a cocktail of lytic phages. No
      increased levels of resistance to phage were found in the wild type compared to a
      recombination deficient DeltadprA strain after five days of evolution. When
      exposed to A. baylyi DNA and phage, naturally transformable cells show greater
      levels of phage resistance. However, increased resistance arose regardless of
      whether they were exposed to DNA from phage-sensitive or -resistant A. baylyi,
      suggesting resistance was not the result of transformation, but was related to
      other benefits of competence. Subsequent evolution in the absence of phages did
      not show that recombination could alleviate the cost of resistance. Within this
      study system we found no support for transformation-mediated recombination being
      an advantage to bacteria exposed to parasitic phages.

PMID- 27869202
TI  - Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral
      Replication.
AB  - Influenza A virus (IAV) is a major human pathogen with the potential to become
      pandemic. IAV contains only eight RNA segments; thus, the virus must fully
      exploit the host cellular machinery to facilitate its own replication. In an
      effort to comprehensively characterize the host machinery taken over by IAV in
      mammalian cells, we generated stable A549 cell lines with over-expression of the
      viral non-structural protein (NS1) to investigate the potential host factors that
      might be modulated by the NS1 protein. We found that the viral NS1 protein
      directly interacted with cellular Rac1 and facilitated viral replication. Further
      research revealed that NS1 down-regulated Rac1 activity via post-translational
      modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated
      host cell signal transduction through the NS1 protein to facilitate its own
      replication. Our findings provide a novel insight into the mechanism of IAV
      replication and indicate new avenues for the development of potential therapeutic
      targets.

PMID- 27869205
TI  - Using instrumental variables to disentangle treatment and placebo effects in
      blinded and unblinded randomized clinical trials influenced by unmeasured
      confounders.
AB  - Clinical trials traditionally employ blinding as a design mechanism to reduce the
      influence of placebo effects. In practice, however, it can be difficult or
      impossible to blind study participants and unblinded trials are common in medical
      research. Here we show how instrumental variables can be used to quantify and
      disentangle treatment and placebo effects in randomized clinical trials comparing
      control and active treatments in the presence of confounders. The key idea is to
      use randomization to separately manipulate treatment assignment and psychological
      encouragement conversations/interactions that increase the participants' desire
      for improved symptoms. The proposed approach is able to improve the estimation of
      treatment effects in blinded studies and, most importantly, opens the doors to
      account for placebo effects in unblinded trials.

PMID- 27869204
TI  - mRNA changes in nucleus accumbens related to methamphetamine addiction in mice.
AB  - Methamphetamine (METH) is a highly addictive psychostimulant that elicits
      aberrant changes in the expression of microRNAs (miRNAs) and long non-coding RNAs
      (lncRNAs) in the nucleus accumbens of mice, indicating a potential role of METH
      in post-transcriptional regulations. To decipher the potential consequences of
      these post-transcriptional regulations in response to METH, we performed strand
      specific RNA sequencing (ssRNA-Seq) to identify alterations in mRNA expression
      and their alternative splicing in the nucleus accumbens of mice following
      exposure to METH. METH-mediated changes in mRNAs were analyzed and correlated
      with previously reported changes in non-coding RNAs (miRNAs and lncRNAs) to
      determine the potential functions of these mRNA changes observed here and how non
      coding RNAs are involved. A total of 2171 mRNAs were differentially expressed in
      response to METH with functions involved in synaptic plasticity, mitochondrial
      energy metabolism and immune response. 309 and 589 of these mRNAs are potential
      targets of miRNAs and lncRNAs respectively. In addition, METH treatment decreases
      mRNA alternative splicing, and there are 818 METH-specific events not observed in
      saline-treated mice. Our results suggest that METH-mediated addiction could be
      attributed by changes in miRNAs and lncRNAs and consequently, changes in mRNA
      alternative splicing and expression. In conclusion, our study reported a
      methamphetamine-modified nucleus accumbens transcriptome and provided non-coding
      RNA-mRNA interaction networks possibly involved in METH addiction.

PMID- 27869206
TI  - Endotoxin free hyaluronan and hyaluronan fragments do not stimulate TNF-alpha,
      interleukin-12 or upregulate co-stimulatory molecules in dendritic cells or
      macrophages.
AB  - The extracellular matrix glycosaminoglycan, hyaluronan, has been described as a
      regulator of tissue inflammation, with hyaluronan fragments reported to stimulate
      innate immune cells. High molecular mass hyaluronan is normally present in
      tissues, but upon inflammation lower molecular mass fragments are generated. It
      is unclear if these hyaluronan fragments induce an inflammatory response or are a
      consequence of inflammation. In this study, mouse bone marrow derived macrophages
      and dendritic cells (DCs) were stimulated with various sizes of hyaluronan from
      different sources, fragmented hyaluronan, hyaluronidases and heavy chain modified
      hyaluronan (HA-HC). Key pro-inflammatory molecules, tumour necrosis factor alpha,
      interleukin-1 beta, interleukin-12, CCL3, and the co-stimulatory molecules, CD40
      and CD86 were measured. Only human umbilical cord hyaluronan, bovine testes and
      Streptomyces hyaluronlyticus hyaluronidase stimulated macrophages and DCs,
      however, these reagents were found to be contaminated with endotoxin, which was
      not fully removed by polymyxin B treatment. In contrast, pharmaceutical grade
      hyaluronan and hyaluronan fragments failed to stimulate in vitro-derived or ex
      vivo macrophages and DCs, and did not induce leukocyte recruitment after
      intratracheal instillation into mouse lungs. Hence, endotoxin-free pharmaceutical
      grade hyaluronan does not stimulate macrophages and DCs in our inflammatory
      models. These results emphasize the importance of ensuring hyaluronan
      preparations are endotoxin free.

PMID- 27869208
TI  - Corrigendum: SparRec: An effective matrix completion framework of missing data
      imputation for GWAS.

PMID- 27869209
TI  - Mitigating effects of ex situ application of rice straw on CH4 and N2O emissions
      from paddy-upland coexisting system.
AB  - The in situ application of rice straw enhances CH4 emissions by a large margin.
      The ex situ application of rice straw in uplands, however, may mitigate total
      global warming potential (GWP) of CH4 and N2O emissions from paddy-upland
      coexisting systems. To evaluate the efficiency of this practice, two field trials
      were conducted in rice-rice-fallow and maize-rape cropping systems, respectively.
      Year-round measurements of CH4 and N2O emissions were conducted to evaluate the
      system-scaled GWP. The results showed that CH4 accounted for more than 98% of GWP
      in paddy. Straw removal from paddy decreased 44.7% (302.1 kg ha-1 yr-1) of CH4
      emissions and 51.2% (0.31 kg ha-1 yr-1) of N2O emissions, thus decreased 44.8%
      (7693 kg CO2-eqv ha-1 yr-1) of annual GWP. N2O accounted for almost 100% of GWP
      in upland. Straw application in upland had insignificant effects on CH4 and N2O
      emissions, which increased GWP only by 91 kg CO2-eqv ha-1 yr-1. So, the transfer
      of straw from paddy to upland could decrease GWP by 7602 kg CO2-eqv ha-1 yr-1.
      Moreover, straw retention during late rice season contributed to 88.2% of annual
      GWP increment. It is recommended to transfer early rice straw to upland
      considering GWP mitigation, nutrient recycling and labor cost.

PMID- 27869207
TI  - Erratum: Control of ADAM17 activity by regulation of its cellular localisation.

PMID- 27869210
TI  - Delivery Room Quality Improvement Project Improved Compliance with Best Practices
      for a Community NICU.
AB  - A Quality Improvement bundle was implemented with the goal of standardizing the
      multidisciplinary approach to delivery room management. We used a Pre-Post
      Quality Improvement initiative with the following aims: (1) Placement of a
      functioning pulse oximeter by two minutes after birth, (2) Delayed intubation,
      (3) Normothermia on Neonatal Intensive Care Unit Admission, (4) Use of a pre
      brief, debrief, and delivery room checklist. Data was collected for 548 infants,
      which represents every admission to the Palomar Rady Children's Hospital Neonatal
      Intensive Care Unit during the 35 month study period from January 1, 2010 to
      November 30, 2012. The intervention began on May 1, 2011. The objective of
      increasing the frequency of each goal was met. A significant decrease in rates of
      retinopathy of prematurity in our post-intervention group was found. Odds ratio
      0.00 (0.000, 0.696) p = 0.008. However, this was not confirmed in the
      multivariable analysis so should be interpreted with caution. This quality
      improvement project had a positive effect on newborn resuscitation at Palomar
      Medical Center.

PMID- 27869211
TI  - Homocysteine and Its Relationship to Asymptomatic Carotid Stenosis in a Chinese
      Community Population.
AB  - Little is known about the association between homocysteine (Hcy) and asymptomatic
      CAS in the healthy population. The purpose of this study was to investigate the
      relationship between Hcy levels and asymptomatic CAS in a Chinese community
      population. The current study included 5393 participants who were age of 40 years
      or older, and free of stroke, transient ischemic attack, and coronary artery
      disease. Demographic and clinical variables were investigated, and the presence
      of CAS was assessed by Color Doppler Ultrasound. A multivariate logistic
      regression was used to examine the association between Hcy levels and
      asymptomatic CAS. 361 (6.69%) participants were diagnosed with asymptomatic CAS,
      who had higher Hcy levels compared with those without (p-value for trend =
      0.0001). After adjusting other possible risk factors, Hcy > 19.3MUmol/L was
      considered as an independent indicator of asymptomatic CAS (OR 1.53, 95%CI 1.05
      2.23; p-value for trend = 0.0265), but with a difference between participants
      with diabetes and without [OR (95%CI): 2.89(1.02-8.22) vs. 1.42(0.95-2.12); P
      interaction < 0.05]. In this large-population, community-based study, Hcy is an
      independent indicator of asymptomatic CAS, especially in patients with diabetes.

PMID- 27869213
TI  - Highly Efficient Spin-Current Operation in a Cu Nano-Ring.
AB  - An all-metal lateral spin-valve structure has been fabricated with a medial
      Copper nano-ring to split the diffusive spin-current path. We have demonstrated
      significant modulation of the non-local signal by the application of a magnetic
      field gradient across the nano-ring, which is up to 30% more efficient than the
      conventional Hanle configuration at room temperature. This was achieved by
      passing a dc current through a current-carrying bar to provide a locally induced
      Ampere field. We have shown that in this manner a lateral spin-valve gains an
      additional functionality in the form of three-terminal gate operation for future
      spintronic logic.

PMID- 27869214
TI  - Irradiance-dependent UVB Photocarcinogenesis.
AB  - Ultraviolet B (UVB) radiation from the sun may lead to photocarcinogenesis of the
      skin. Sunscreens were used to protect the skin by reducing UVB irradiance, but
      sunscreen use did not reduce sunburn episodes. It was shown that UVB-induced
      erythema depends on surface exposure but not irradiance of UVB. We previously
      showed that irradiance plays a critical role in UVB-induced cell differentiation.
      This study investigated the impact of irradiance on UVB-induced
      photocarcinogenesis. For hairless mice receiving equivalent exposure of UVB
      radiation, the low irradiance (LI) UVB treated mice showed more rapid tumor
      development, larger tumor burden, and more keratinocytes harboring mutant p53 in
      the epidermis as compared to their high irradiance (HI) UVB treated counterpart.
      Mechanistically, using cell models, we demonstrated that LI UVB radiation allowed
      more keratinocytes harboring DNA damages to enter cell cycle via ERK-related
      signaling as compared to its HI UVB counterpart. These results indicated that at
      equivalent exposure, UVB radiation at LI has higher photocarcinogenic potential
      as compared to its HI counterpart. Since erythema is the observed sunburn at
      moderate doses and use of sunscreen was not found to associate with reduced
      sunburn episodes, the biological significance of sunburn with or without
      sunscreen use warrants further investigation.

PMID- 27869216
TI  - Erratum: Lipid membrane-mediated attraction between curvature inducing objects.

PMID- 27869212
TI  - The ERF transcription factor family in cassava: genome-wide characterization and
      expression analyses against drought stress.
AB  - Cassava (Manihot esculenta) shows strong tolerance to drought stress; however,
      the mechanisms underlying this tolerance are poorly understood. Ethylene response
      factor (ERF) family genes play a crucial role in plants responding to abiotic
      stress. Currently, less information is known regarding the ERF family in cassava.
      Herein, 147 ERF genes were characterized from cassava based on the complete
      genome data, which was further supported by phylogenetic relationship, gene
      structure, and conserved motif analyses. Transcriptome analysis suggested that
      most of the MeERF genes have similar expression profiles between W14 and Arg7
      during organ development. Comparative expression profiles revealed that the
      function of MeERFs in drought tolerance may be differentiated in roots and leaves
      of different genotypes. W14 maintained strong tolerance by activating more MeERF
      genes in roots compared to Arg7 and SC124, whereas Arg7 and SC124 maintained
      drought tolerance by inducing more MeERF genes in leaves relative to W14.
      Expression analyses of the selected MeERF genes showed that most of them are
      significantly upregulated by osmotic and salt stresses, whereas slightly induced
      by cold stress. Taken together, this study identified candidate MeERF genes for
      genetic improvement of abiotic stress tolerance and provided new insights into
      ERF-mediated cassava tolerance to drought stress.

PMID- 27869215
TI  - Crosstalk between sugarcane and a plant-growth promoting Burkholderia species.
AB  - Bacterial species in the plant-beneficial-environmental clade of Burkholderia
      represent a substantial component of rhizosphere microbes in many plant species.
      To better understand the molecular mechanisms of the interaction, we combined
      functional studies with high-resolution dual transcriptome analysis of sugarcane
      and root-associated diazotrophic Burkholderia strain Q208. We show that
      Burkholderia Q208 forms a biofilm at the root surface and suppresses the
      virulence factors that typically trigger immune response in plants. Up-regulation
      of bd-type cytochromes in Burkholderia Q208 suggests an increased energy
      production and creates the microaerobic conditions suitable for BNF. In this
      environment, a series of metabolic pathways are activated in Burkholderia Q208
      implicated in oxalotrophy, microaerobic respiration, and formation of PHB
      granules, enabling energy production under microaerobic conditions. In the plant,
      genes involved in hypoxia survival are up-regulated and through increased
      ethylene production, larger aerenchyma is produced in roots which in turn
      facilitates diffusion of oxygen within the cortex. The detected changes in gene
      expression, physiology and morphology in the partnership are evidence of a
      sophisticated interplay between sugarcane and a plant-growth promoting
      Burkholderia species that advance our understanding of the mutually beneficial
      processes occurring in the rhizosphere.

PMID- 27869217
TI  - Magnesium alloy covered stent for treatment of a lateral aneurysm model in rabbit
      common carotid artery: An in vivo study.
AB  - Magnesium alloy covered stents have rarely been used in the common carotid artery
      (CCA). We evaluated the long-term efficacy of magnesium alloy covered stents in a
      lateral aneurysm model in rabbit CCA. Magnesium alloy covered stents (group A, n
      = 7) or Willis covered stents (group B, n = 5) were inserted in 12 New Zealand
      White rabbits and they were followed up for 12 months. The long-term feasibility
      for aneurysm occlusion was studied through angiograms; the changes in vessel area
      and lumen area were assessed with IVUS. Complete aneurysmal occlusion was
      achieved in all aneurysms. Angiography showed that the diameter of the stented
      CCA in group A at 6 and 12 months was significantly greater than the diameter
      immediately after stent placement. On intravascular ultrasound (IVUS)
      examination, the mean lumen area of the stented CCA in group A was significantly
      greater at 6 and 12 months than that immediately after stent placement; the mean
      lumen area was also significantly greater in group A than in group B at the same
      time points. The magnesium alloy covered stents proved to be an effective
      approach for occlusion of lateral aneurysm in the rabbit CCA; it provides
      distinct advantages that are comparable to that obtained with the Willis covered
      stent.

PMID- 27869220
TI  - Using the virtual reality device Oculus Rift for neuropsychological assessment of
      visual processing capabilities.
AB  - Neuropsychological assessment of human visual processing capabilities strongly
      depends on visual testing conditions including room lighting, stimuli, and
      viewing-distance. This limits standardization, threatens reliability, and
      prevents the assessment of core visual functions such as visual processing speed.
      Increasingly available virtual reality devices allow to address these problems.
      One such device is the portable, light-weight, and easy-to-use Oculus Rift. It is
      head-mounted and covers the entire visual field, thereby shielding and
      standardizing the visual stimulation. A fundamental prerequisite to use Oculus
      Rift for neuropsychological assessment is sufficient test-retest reliability.
      Here, we compare the test-retest reliabilities of Bundesen's visual processing
      components (visual processing speed, threshold of conscious perception, capacity
      of visual working memory) as measured with Oculus Rift and a standard CRT
      computer screen. Our results show that Oculus Rift allows to measure the
      processing components as reliably as the standard CRT. This means that Oculus
      Rift is applicable for standardized and reliable assessment and diagnosis of
      elementary cognitive functions in laboratory and clinical settings. Oculus Rift
      thus provides the opportunity to compare visual processing components between
      individuals and institutions and to establish statistical norm distributions.

PMID- 27869221
TI  - In-situ nano-crystal-to-crystal transformation synthesis of energetic materials
      based on three 5,5'-azotetrazolate Cr(III) salts.
AB  - The in-situ nano-crystal-to-crystal transformation (SCCT) synthesis provides a
      powerful approach for tailoring controllable feature shapes and sizes of nano
      crystals. In this work, three nitrogen-rich energetic nano-crystals based on 5,5'
      azotetrazolate(AZT2-) Cr(III) salts were synthesized by means of SCCT
      methodology. SEM and TEM analyses show that the energetic nano-crystals feature a
      composition- and structure-dependent together with size-dependent thermal
      stability. Moreover, nano-scale decomposition products can be obtained above 500 
      degrees C, providing a new method for preparing metallic oxide nano materials.

PMID- 27869218
TI  - N-linked glycosylation at Asn152 on CD147 affects protein folding and stability:
      promoting tumour metastasis in hepatocellular carcinoma.
AB  - Cluster of differentiation 147 (CD147), also known as extracellular matrix
      metalloproteinase inducer, is a transmembrane glycoprotein that mediates
      oncogenic processes partly through N-glycosylation modifications. N-glycosylation
      has been demonstrated to be instrumental for the regulation of CD147 function
      during malignant transformation. However, the role that site-specific
      glycosylation of CD147 plays in its defective function in hepatocellular
      carcinomacells needs to be determined. Here, we demonstrate that the modification
      of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma
      (HCC) invasion and migration. After the removal of N-glycans at Asn152, CD147 was
      more susceptible to degradation by ER-localized ubiquitin ligase-mediated
      endoplasmic reticulum-associated degradation (ERAD). Furthermore, N-linked
      glycans at Asn152 were required for CD147 to acquire and maintain proper folding
      in the ER. Moreover, N-linked glycans at Asn152 functioned as a recognition motif
      that was directly mediated by the CNX quality control system. Two phases in the
      retention-based ER chaperones system drove ER-localized CD147 trafficking to
      degradation. Deletion of N-linked glycosylation at Asn152 on CD147 significantly
      suppressed in situ tumour metastasis. These data could potentially shed light on
      the molecular regulation of CD147 through glycosylation and provide a valuable
      means of developing drugs that target N-glycans at Asn152 on CD147.

PMID- 27869219
TI  - A Novel Role of Spred2 in the Colonic Epithelial Cell Homeostasis and
      Inflammation.
AB  - Rapid and adequate mucosal healing is important for a remission of ulcerative
      colitis (UC) patients. Here, we examined whether Spred2, a member of the Sprouty
      related EVH1-domain-containing proteins that inhibit the Ras/Raf/ERK pathway,
      plays a role in colonic mucosal homeostasis and inflammation by using Spred2
      knockout (KO) mice. We first detected increased epithelial cell proliferation and
      cadherin 1 expression in the colon of naive Spred2 KO mice compared to wild-type
      mice. Interestingly, Spred2 KO mice were resistant to dextran sulfate sodium
      (DSS)-induced acute colitis as indicated by lower levels of body weight loss and
      disease activity index. Histologically, epithelial cell injury and inflammation
      were milder in the colonic mucosa of Spred2 KO mice on day 3 and almost
      undetectable by day 8. Experiments with bone chimeric mice indicated that Spred2
      deficiency in non-hematopoietic cells was responsible for the reduced sensitivity
      to DSS. Finally, Spred2 KO mice developed significantly fewer tumors in response
      to azoxymethane plus DSS. Taken together, our results demonstrate, for the first
      time, that Spred2 plays an important role in the regulation of colonic epithelial
      cell proliferation and inflammation by potentially down-regulating the activation
      of ERK. Thus, Spred2 may be a new therapeutic target for the treatment of UC.

PMID- 27869222
TI  - Investigation of AlGaN/GaN high electron mobility transistor structures on 200-mm
      silicon (111) substrates employing different buffer layer configurations.
AB  - AlGaN/GaN high electron mobility transistor (HEMT) structures are grown on 200-mm
      diameter Si(111) substrates by using three different buffer layer configurations:
      (a) Thick-GaN/3 * {AlxGa1-xN}/AlN, (b) Thin-GaN/3 * {AlxGa1-xN}/AlN, and (c) Thin
      GaN/AlN, so as to have crack-free and low-bow (<50 MUm) wafer. Scanning electron
      microscopy, energy-dispersive X-ray spectroscopy, high resolution-cross section
      transmission electron microscopy, optical microscopy, atomic-force microscopy,
      cathodoluminescence, Raman spectroscopy, X-ray diffraction (omega/2theta scan and
      symmetric/asymmetric omega scan (rocking curve scan), reciprocal space mapping)
      and Hall effect measurements are employed to study the structural, optical, and
      electrical properties of these AlGaN/GaN HEMT structures. The effects of buffer
      layer stacks (i.e. thickness and content) on defectivity, stress, and two
      dimensional electron gas (2DEG) mobility and 2DEG concentration are reported. It
      is shown that 2DEG characteristics are heavily affected by the employed buffer
      layers between AlGaN/GaN HEMT structures and Si(111) substrates. Particularly, we
      report that in-plane stress in the GaN layer affects the 2DEG mobility and 2DEG
      carrier concentration significantly. Buffer layer engineering is shown to be
      essential for achieving high 2DEG mobility (>1800 cm2/V?s) and 2DEG carrier
      concentration (>1.0 * 1013 cm-2) on Si(111) substrates.

PMID- 27869223
TI  - Insight into the metabolic mechanism of scoparone on biomarkers for inhibiting
      Yanghuang syndrome.
AB  - Scoparone (6,7-dimethoxycoumarin) is the representative ingredient of Yinchenhao
      (Artemisia capillaris Thunb.) which is a famous Chinese medicinal herb and shows
      favorable efficacy for all kinds of liver disease, specifically for the treatment
      of Yanghuang syndrome (YHS). The precise molecular mechanism concerning the
      action of scoparone on YHS is yet to be fully elucidated. The aim of the present
      study was to determine the mechanism of scoparone and evaluate its efficacy on
      metabolite levels. The differential expression of metabolites responsible for the
      pharmacological effects of scoparone was characterized and the protection effect
      of scoparone against this disease. Using multivariate statistical analysis, 33
      biomarkers were identified using precise MS/MS and play an important role in the
      regulation of key metabolic pathways associated with liver disease. In addition,
      pathological results also showed consistent changes in the YHS model group and
      after treatment with scoparone, both the metabolic profile and histopathology
      resembled that of normal level, which suggesting favorable efficacy over the
      observed time period. The present work indicated that a metabolomics platform
      provided a new insight into understanding the mechanisms of action of natural
      medicines such as scoparone.

PMID- 27869224
TI  - Selection of reliable reference genes for normalization of quantitative RT-PCR
      from different developmental stages and tissues in amphioxus.
AB  - Amphioxus is a closest living proxy to the ancestor of cephalochordates with
      vertebrates, and key animal for novel understanding in the evolutionary origin of
      vertebrate body plan, genome, tissues and immune system. Reliable analyses using
      quantitative real-time PCR (qRT-PCR) for answering these scientific questions is
      heavily dependent on reliable reference genes (RGs). In this study, we evaluated
      stability of thirteen candidate RGs in qRT-PCR for different developmental stages
      and tissues of amphioxus by four independent (geNorm, NormFinder, BestKeeper and
      deltaCt) and one comparative algorithms (RefFinder). The results showed that the
      top two stable RGs were the following: (1) S20 and 18 S in thirteen developmental
      stages, (2) EF1A and ACT in seven normal tissues, (3) S20 and L13 in both
      intestine and hepatic caecum challenged with lipopolysaccharide (LPS), and (4)
      S20 and EF1A in gill challenged with LPS. The expression profiles of two target
      genes (EYA and HHEX) in thirteen developmental stages were used to confirm the
      reliability of chosen RGs. This study identified optimal RGs that can be used to
      accurately measure gene expression under these conditions, which will benefit
      evolutionary and functional genomics studies in amphioxus.

PMID- 27869225
TI  - Noisy galvanic vestibular stimulation induces a sustained improvement in body
      balance in elderly adults.
AB  - Vestibular dysfunction causes postural instability, which is prevalent in the
      elderly. We previously showed that an imperceptible level of noisy galvanic
      vestibular stimulation (nGVS) can improve postural stability in patients with
      bilateral vestibulopathy during the stimulus, presumably by enhancing vestibular
      information processing. In this study, we investigated the after-effects of an
      imperceptible long-duration nGVS on body balance in elderly adults. Thirty
      elderly participants underwent two nGVS sessions in a randomised order. In
      Session 1, participants received nGVS for 30 min twice with a 4-h interval. In
      Session 2, participants received nGVS for 3 h. Two-legged stance tasks were
      performed with eyes closed while participants stood on a foam rubber surface,
      with and without nGVS, and parameters related to postural stability were measured
      using posturography. In both sessions, the postural stability was markedly
      improved for more than 2 h after the cessation of the stimulus and tended to
      decrease thereafter. The second stimulation in Session 1 caused a moderate
      additional improvement in body balance and promoted the sustainability of the
      improvement. These results suggest that nGVS can lead to a postural stability
      improvement in elderly adults that lasts for several hours after the cessation of
      the stimulus, probably via vestibular neuroplasticity.

PMID- 27869226
TI  - The effects of manganese oxide octahedral molecular sieve chitosan microspheres
      on sludge bacterial community structures during sewage biological treatment.
AB  - This study examines the effects of manganese oxide octahedral molecular sieve
      chitosan microspheres (Fe3O4@OMS-2@CTS) on anaerobic and aerobic microbial
      communities during sewage biological treatment. The addition of Fe3O4@OMS-2@CTS
      (0.25 g/L) resulted in enhanced levels of operational performance for
      decolourization dye X-3B. However, degradation dye X-3B inhibition in the
      presence of Fe3O4@OMS-2@CTS was recorded as greater than or equal to 1.00 g/L.
      Illumina MiSeq high throughput sequencing of the 16 S rRNA gene showed that 108
      genera were observed during the anaerobic process, while only 71 genera were
      observed during the aerobic process. The largest genera (Aequorivita) decreased
      from 21.14% to 12.65% and the Pseudomonas genera increased from 10.57% to 12.96%
      according to the abundance in the presence of 0.25 g/L Fe3O4@OMS-2@CTS during the
      anaerobic process. The largest Gemmatimonas genera decreased from 21.46% to
      11.68% and the Isosphaerae genera increased from 5.8% to 11.98% according to the
      abundance in the presence of 0.25 g/L Fe3O4@OMS-2@CTS during the aerobic process.
      Moreover, the X-ray photoelectron spectroscopy results show that the valence
      states of Mn and Fe in Fe3O4@OMS-2@CTS changed during sewage biological
      treatment.

PMID- 27869228
TI  - Catalytic conversion of lignin pyrolysis model compound- guaiacol and its kinetic
      model including coke formation.
AB  - Lignin is the most difficult to be converted and most easy coking component in
      biomass catalytic pyrolysis to high-value liquid fuels and chemicals. Catalytic
      conversion of guaiacol as a lignin model compound was conducted in a fixed-bed
      reactor over ZSM-5 to investigate its conversion and coking behaviors. The
      effects of temperature, weight hourly space velocity (WHSV) and partial pressure
      on product distribution were studied. The results show the maximum aromatic
      carbon yield of 28.55% was obtained at temperature of 650  degrees C, WHSV of 8 h
      1 and partial pressure of 2.38 kPa, while the coke carbon yield was 19.55%. The
      reaction pathway was speculated to be removing methoxy group to form phenols with
      further aromatization to form aromatics. The amount of coke increased with
      increasing reaction time. The surface area and acidity of catalysts declined as
      coke formed on the acid sites and blocked the pore channels, which led to the
      decrease of aromatic yields. Finally, a kinetic model of guaiacol catalytic
      conversion considering coke deposition was built based on the above reaction
      pathway to properly predict product distribution. The experimental and model
      predicting data agreed well. The correlation coefficient of all equations were
      all higher than 0.90.

PMID- 27869227
TI  - Hypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells:
      Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin.
AB  - Vasculogenic mimicry (VM) plays an important role in colorectal cancer (CRC)
      metastasis, and both hypoxia and the epithelial-mesenchymal transition (EMT) are
      necessary for VM. In this study, HIF-1alpha expression was upregulated in the VM
      positive CRC cell line HCT-116 and thereby affected the expression of the EMT
      related markers Claudin-4, E-cadherin (E-cd) and Vimentin(VIM). SB431542 and
      U0126EtOH, which can inhibit of EMT were used to treat HCT-116 and HCT-8 in these
      experiments. Both of the inhibitors had significant effect on EMT markers and the
      formations of VM in CRC cells. In addition, knockdown of HIF-1alpha in the HCT
      116 cells inhibited their capacity for VM. Our study reveals a regulatory role
      for HIF-1alpha in VM and suggests that targeting either HIF-1alpha or EMT may be
      a valuable strategy for the elimination of CRC metastasis.

PMID- 27869231
TI  - GeS2-In2S3-CsI Chalcogenide Glasses Doped with Rare Earth Ions for Near- and Mid
      IR Luminescence.
AB  - Chalcogenide glass has been considered as a promising host for the potential
      laser gain and amplifier media operating in near- and mid-IR spectral region. In
      this work, the IR luminescence spectra of rare earth ions (Tm3+, Er3+, and Dy3+)
      doped 65GeS2-25In2S3-10CsI chalcogenide glasses were measured under the
      excitation of an 808 nm laser diode. To the best of our knowledge, it firstly
      provides the luminescence spectra of a full near- and mid-IR spectral range from
      1 to 4 MUm in rare earth ions doped chalcogenide glasses. The results of
      absorption spectra, luminescence spectra, and fluorescence decay curves were
      obtained in these samples with singly-, co- and triply-doping behaviors of Tm3+,
      Er3+, and Dy3+ ions. In order to search possible efficient IR emissions, the
      luminescence behavior was investigated specifically with the variation of doping
      behaviors and dopant ions, especially in the samples co- and triply-doped active
      ions. The results suggest that favorable near- and mid-IR luminescence of rare
      earth ions can be further modified in chalcogenide glasses through an elaborated
      design of doping behavior and optically active ions.

PMID- 27869230
TI  - A graph-theoretical representation of multiphoton resonance processes in
      superconducting quantum circuits.
AB  - We propose a graph-theoretical formalism to study generic circuit quantum
      electrodynamics systems consisting of a two level qubit coupled with a single
      mode resonator in arbitrary coupling strength regimes beyond rotating-wave
      approximation. We define colored-weighted graphs, and introduce different
      products between them to investigate the dynamics of superconducting qubits in
      transverse, longitudinal, and bidirectional coupling schemes. The intuitive and
      predictive picture provided by this method, and the simplicity of the
      mathematical construction, are demonstrated with some numerical studies of the
      multiphoton resonance processes and quantum interference phenomena for the
      superconducting qubit systems driven by intense ac fields.

PMID- 27869232
TI  - Corrigendum: Bioluminescence Microscopy as a Method to Measure Single Cell
      Androgen Receptor Activity Heterogeneous Responses to Antiandrogens.

PMID- 27869229
TI  - Tetratricopeptide repeat domain 9A modulates anxiety-like behavior in female
      mice.
AB  - Tetratricopeptide repeat domain 9A (TTC9A) expression is abundantly expressed in
      the brain. Previous studies in TTC9A knockout (TTC9A-/-) mice have indicated that
      TTC9A negatively regulates the action of estrogen. In this study we investigated
      the role of TTC9A on anxiety-like behavior through its functional interaction
      with estrogen using the TTC9A-/- mice model. A battery of tests on anxiety
      related behaviors was conducted. Our results demonstrated that TTC9A-/- mice
      exhibited an increase in anxiety-like behaviors compared to the wild type
      TTC9A+/+ mice. This difference was abolished after ovariectomy, and
      administration of 17-beta-estradiol benzoate (EB) restored this escalated anxiety
      like behavior in TTC9A-/- mice. Since serotonin is well-known to be the key
      neuromodulator involved in anxiety behaviors, the mRNA levels of tryptophan
      hydroxylase (TPH) 1, TPH2 (both are involved in serotonin synthesis), and
      serotonin transporter (5-HTT) were measured in the ventromedial prefrontal cortex
      (vmPFC) and dorsal raphe nucleus (DRN). Interestingly, the heightened anxiety in
      TTC9A-/- mice under EB influence is consistent with a greater induction of TPH 2,
      and 5-HTT by EB in DRN that play key roles in emotion regulation. In conclusion,
      our data indicate that TTC9A modulates the anxiety-related behaviors through
      modulation of estrogen action on the serotonergic system in the DRN.

PMID- 27869235
TI  - Interactions of the Greater Ontong Java mantle plume component with the Osbourn
      Trough.
AB  - The Ontong Java-Manihiki-Hikurangi plateau (OJMHP) is considered to have
      originated from a starting mantle plume, and have been rifted apart by two
      spreading ridges. However, the ages of these spreading ridges and their possible
      interactions with the presumed mantle plume are unclear. The Manihiki-Hikurangi
      plateau has been rifted apart by the Osbourn Trough which formed the southwestern
      Pacific crust to the east of the Tonga-Kermadec trench. Here we report Pb-Hf-Os
      isotopes of the basaltic crust (Site U1365 of IODP Expedition 329) formed by the
      Osbourn Trough. Linear regression of Re-Os isotopes results in an age of 103.7 +/
      2.3 Ma for Site U1365 basalts, indicating that the Manihiki-Hikurangi plateau
      was rifted apart by the Osbourn Trough with a spreading rate of ~190 mm/yr. The
      superfast spreading rate supports the Osbourn as an abandoned segment of the
      early Pacific spreading ridge, which initially overlapped with the giant starting
      plume. Moreover, the Pb-Hf isotopes of some of Site U1365 basalts show distinct
      differences from those of the Pacific mid-ocean ridge basalts, while they are
      similar to the basalts of the Ontong Java and Manihiki plateaus. We suggest that
      the OJMHP mantle plume components has been involved by the Osbourn spreading
      center.

PMID- 27869234
TI  - Autoimmune susceptibility imposed by public TCRbeta chains.
AB  - Although the TCR repertoire is highly diverse, a small fraction of TCR chains,
      referred to as public, preferentially form and are shared by most individuals.
      Prior studies indicated that public TCRbeta may be preferentially deployed in
      autoimmunity. We hypothesized that if these TCRbeta modulate the likelihood of a
      TCRalphabeta heterodimer productively engaging autoantigen, because they are
      widely present in the population and often high frequency within individual
      repertoires, they could also broadly influence repertoire responsiveness to
      specific autoantigens. We assess this here using a series of public and private
      TCRbeta derived from autoimmune encephalomyelitis-associated TCR. Transgenic
      expression of public, but not private, disease-associated TCRbeta paired with
      endogenously rearranged TCRalpha endowed unprimed T cells with autoantigen
      reactivity. Further, two of six public, but none of five private TCRbeta provoked
      spontaneous early-onset autoimmunity in mice. Our findings indicate that single
      TCRbeta are sufficient to confer on TCRalphabeta chains reactivity toward disease
      associated autoantigens in the context of diverse TCRalpha. They further suggest
      that public TCR can skew autoimmune susceptibility, and that subsets of public
      TCR sequences may serve as disease- specific biomarkers or therapeutic targets.

PMID- 27869233
TI  - Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi
      Screen in Mammalian Embryos.
AB  - With readily available transcriptome-wide data, understanding the role of each
      expressed gene is an essential next step. Although RNAi technologies allow for
      genome-wide screens in cell culture, these approaches cannot replace strategies
      for discovery in the embryo. Here we present, for the first time, a knockdown
      screen in mouse preimplantation embryos. Early mammalian development encompasses
      dynamic cellular, molecular and epigenetic events that are largely conserved from
      mouse to man. We assayed 712 genes for requirements during preimplantation. We
      identified 59 genes required for successful development or outgrowth and
      implantation. We have characterized each phenotype and revealed cellular,
      molecular, and lineage specific defects following knockdown of transcript.
      Induced network analyses demonstrate this as a valid approach to identify
      networks of genes that play important roles during preimplantation. Our approach
      provides a robust and efficient strategy towards identification of novel
      phenotypes during mouse preimplantation and facilitates functional annotation of
      the mammalian transcriptome.

PMID- 27869236
TI  - Sleep duration and metabolic syndrome.

PMID- 27869237
TI  - Validity of mesothelin in occupational medicine practice.

PMID- 27869238
TI  - Response to the letter to editors concerning "Validity of mesothelin in
      occupational medicine practice".

PMID- 27869239
TI  - Polish Mother and Child Cohort Study (REPRO_PL) - Methodology of the follow-up of
      the children at the age of 7.
AB  - Effects of environmental exposures in utero and in the first years of life on
      early life health and development is a growing research area with major public
      health implications. The main aim of this work has been to provide an overview of
      the next step of the Polish Mother and Child Cohort Study (REPRO_PL) covering
      exposure, health and neurodevelopment assessments of children at 7 years of age.
      Details regarding methodology of the follow-up of the children are crucial for
      cross-cohort collaboration and a full understanding of the future research
      questions. Phase III of the REPRO_PL cohort covers a follow-up of 900 children at
      the age of 7 years old. The questionnaire filled in by the mothers is composed
      of: socio-demographic, child exposure and home environment information,
      nutritional status and health data. In the case of 400 children, environmental
      (including collection of urine, saliva and buccal cells), health status and
      psychomotor assessments are performed. Health and development check consists of
      physical measurements, child health status assessment (including lung function
      tests, skin prick testing, an interview/examination by an allergist) and
      psychomotor development tests (the Strength and Difficulties Questionnaire and
      the Intelligence and Development Scales). The results of the study will become
      available within the next few years. Extension of the REPRO_PL cohort with
      examinations of children at the age of 7 years old may provide a better
      understanding of the relationship between environmental and lifestyle-related
      factors and children's health and neurodevelopment; and may further strengthen
      scientific base for policies and interventions promoting healthy lifestyle. Int J
      Occup Med Environ Health 2016;29(6):883-893.

PMID- 27869240
TI  - Relationship between occupational stress and cardiovascular diseases risk factors
      in drivers.
AB  - OBJECTIVES: Of all work stressors, occupational stress is the leading cause of
      many disorders among workers. Drivers are classified as a high risk group for
      work related stress. This study set out to determine the relationship between
      risk factors of cardiovascular diseases and occupational stress among drivers.
      MATERIAL AND METHODS: Two hundred and twenty two Ilam's intercity drivers were
      selected for the study. For measuring work stress, the Osipow work stress
      questionnaire was used. After a 10-h fasting period, systolic and diastolic blood
      pressure was recorded. Intravenous blood samples were taken to determine
      cholesterol, triglyceride and blood glucose levels. The independent samples t
      test and Pearson's correlation test were used to assess the relationship between
      variables and occupational stress. RESULTS: Seventy-one percent of the intercity
      drivers suffered from average to acute stress, and 3.1% of them suffered from
      acute stress. There was no significant relationship between occupational stress
      and diastolic blood pressure (p = 0.254) among the drivers. Nevertheless, the
      Pearson's correlation test demonstrated a strong relationship between work stress
      and blood glucose (p < 0.01), while no strong correlation was found for blood
      triglycerides and cholesterol levels. CONCLUSIONS: Based on the results, high
      rates of occupational stress were observed in the Ilam's intercity drivers.
      Occupational stress may have effect on blood glucose levels but the results did
      not suggest a considerable relationship between risk factors of cardiovascular
      diseases and occupational stress among intercity drivers. Int J Occup Med Environ
      Health 2016;29(6):895-901.

PMID- 27869241
TI  - New market labor and obesity: A nation-wide Italian cross-sectional study.
AB  - OBJECTIVES: To investigate the prevalence of obesity among different types of
      employment status in the Italian working population, and to examine associated
      risk factors. MATERIAL AND METHODS: Cross-sectional survey of 36 814 people that
      declared to have been occupied with the same type of contract for at least 5
      years was analyzed. Multivariable logistic regression models were built
      considering workers' sex, age, education, family body mass index (BMI) category,
      leisure time and occupational physical activity, weight control habits, smoking
      habit, use of drugs, number of working hours per week, and type of working
      contract. RESULTS: After adjusting for covariates, the importance of temporary
      employment was confirmed by multivariate analysis, with odds ratio (OR) = 1.32
      for obesity (95% confidence interval (CI): 1.07-1.63) with respect to employed
      persons; the association was even more important in workers occupied for more
      than 40 h/week (OR = 1.69, 95% CI: 1.07-2.66); moreover, shiftwork was confirmed
      as a risk factor for obesity in workers (OR = 1.06, 95% CI: 0.94-1.2). Dealing
      with different occupational group, some categories were associated with obesity;
      in particular, this phenomenon involved people employed in agriculture (OR =
      1.44, 95% CI: 1.22-1.7), transportation (OR = 1.53, 95% CI: 1.26-1.85), and
      public administration (OR = 1.31, 95% CI: 1.1-1.55). CONCLUSIONS: Our analysis
      suggest that obesity is strongly correlated with temporary employment. Maybe the
      way out this pathway to obesity in the future might be working better, choosing
      organizational flexibility rather than fixed term. Int J Occup Med Environ Health
      2016;29(6):903-914.

PMID- 27869242
TI  - Sperm quality and DNA integrity of coke oven workers exposed to polycyclic
      aromatic hydrocarbons.
AB  - OBJECTIVES: The objective of this study was to assess sperm quality and
      deoxyribonucleic acid (DNA) integrity of coke oven workers exposed to polycyclic
      aromatic hydrocarbons (PAHs) as compared to control subjects. MATERIAL AND
      METHODS: The coke oven workers (N = 52) and administrative staff (N = 35) of a
      steel plant served as the exposed and control groups, respectively. Exposure to
      PAHs was assessed by measuring 1-hydroxypyren. Analysis of sperm quality
      (concentration, motility, vitality, and morphology) was performed simultaneously
      with sperm DNA integrity analysis, including DNA fragmentation, denaturation,
      bulky DNA adducts, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo). A
      questionnaire was conducted to collect demographic and potential confounding
      data. RESULTS: The coke oven workers had lower percentages of sperm motility,
      vitality and normal morphology than the control group, but the difference was not
      significant. For DNA integrity, the coke oven workers had significantly higher
      concentrations of bulky DNA adducts and 8-oxo-dGuo than the control subjects (p =
      0.009 and p = 0.048, respectively). However, DNA fragmentation percentages did
      not significantly increase as compared to those in the subjects from the control
      group (p = 0.232). There was no correlation between sperm quality parameters and
      DNA integrity indicators. CONCLUSIONS: Occupational exposure of the coke oven
      workers to PAHs was associated with decreased sperm DNA integrity. Int J Occup
      Med Environ Health 2016;29(6):915-926.

PMID- 27869243
TI  - Personal risk factors for carpal tunnel syndrome in female visual display unit
      workers.
AB  - OBJECTIVES: Carpal tunnel syndrome (CTS) is the most common nerve entrapment
      syndrome, which since the beginning of the seventies has been linked to the
      keyboard and visual display unit (VDU). The objective of this study was to
      investigate the prevalence and personal factors associated with CTS in female VDU
      workers in Italy. MATERIAL AND METHODS: Participants in this study were female
      adult subjects, working >= 20 h/week (N = 631, mean age 38.14+/-7.81 years, mean
      working age 12.9+/-7.24 years). Signs and symptoms were collected during
      compulsory occupational medical surveillance. The binary logistic regression was
      used to estimate adjusted odds ratios for the factors of interest. RESULTS:
      Diagnosis of CTS was reported in 48 cases (7.6%, 11 of them or 1.7% after a
      surgical correction) for the incidence of 5.94/1000 person-years. In general,
      signs and symptoms of CTS were associated with the following demographic factors:
      previous trauma of upper limb (adjusted odds ratio (ORa) = 8.093, 95% confidence
      interval (CI): 2.347-27.904), history (> 5 years) of oral contraceptives
      therapy/hormone replacement therapy (ORa = 3.77, 95% CI: 1.701-8.354) and
      cervical spine signs/symptoms (ORa = 4.565, 95% CI: 2.281-9.136). CONCLUSIONS:
      The prevalence of CTS was similar to the estimates for the general population of
      Italy. Among personal risk factors, hormone therapy, previous trauma of the upper
      limb and signs/symptoms of the cervical spine appeared to be associated with a
      higher risk of CTS syndrome. Eventually, the results reinforce interpretation of
      CTS in VDU workers as a work-related musculoskeletal disorder rather than a
      classical occupational disease. Int J Occup Med Environ Health 2016;29(6):927
      936.

PMID- 27869244
TI  - Multi-instrument assessment of physical activity in female office workers.
AB  - OBJECTIVES: The aim of this study was to examine the multi-instrument assessment
      of physical activity in female office workers. MATERIAL AND METHODS: Fifty
      healthy women (age (mean +/- standard deviation): 34.8+/-5.9 years, body height:
      158+/-0.4 cm, body weight: 61.8+/-7.5 kg, body mass index: 24.6+/-2.7
      kg/m<sup>2</sup>) workers from the same workplace volunteered to participate in
      the study. Physical activity was measured with the 7-day Physical Activity
      Assessment Questionnaire (7-d PAAQ), an objective multi-sensor armband tool, and
      also a waist-mounted pedometer, which were both worn for 7 days. RESULTS: A
      significant correlation between step numbers measured by armband and pedometer
      was observed (r = 0.735), but the step numbers measured by these 2 methods were
      significantly different (10 941+/-2236 steps/ day and 9170+/-2377 steps/day,
      respectively; p < 0.001). There was a weak correlation between the value of 7-d
      PAAQ total energy expenditure and the value of armband total energy expenditure
      (r = 0.394, p = 0.005). However, total energy expenditure values measured by
      armband and 7-d PAAQ were not significantly different (2081+/-370 kcal/ day and
      2084+/-197 kcal/day, respectively; p = 0.96). In addition, physical activity
      levels (average daily metabolic equivalents (MET)) measured by armband and 7-d
      PAAQ were not significantly different (1.45+/-0.12 MET/day and 1.47+/-0.24
      MET/day, respectively; p = 0.44). CONCLUSIONS: The results of this study showed
      that the correlation between pedometer and armband measurements was higher than
      that between armband measurements and 7-d PAAQ selfreports. Our results suggest
      that none of the assessment methods examined here, 7-d PAAQ, pedometer, or
      armband, is sufficient when used as a single tool for physical activity level
      determination. Therefore, multi-instrument assessment methods are preferable. Int
      J Occup Med Environ Health 2016;29(6):937-945.

PMID- 27869245
TI  - Predictors of early return to work after a coronary artery bypass graft surgery
      (CABG).
AB  - OBJECTIVES: Identifying factors predictive of early return to work in patients
      who underwent a coronary artery bypass graft surgery (CABG). MATERIAL AND
      METHODS: Two hundred twenty-six working patients who volunteered and underwent a
      primary coronary artery bypass surgery between September 2013 and May 2014 were
      selected for the study and followed up for 6 months. Predictors of early return
      to work (RTW) (within 2 months) were analyzed from variables in a prospectively
      collected database and the 36-Item Short Form Health Survey (SF-36) questionnaire
      carried out in the hospital and rehabilitation center as well as from the follow
      up performed via the phone. RESULTS: One hundred and two (45.1%) and 155 (68.9%)
      patients returned to work within 2 and 3 months after the surgery, respectively.
      Furthermore, 196 patients (87.1%) returned to work within 6 months after the
      surgery. In the univariate analysis, demographic or socioeconomic factors (such
      as age, level of education, income), occupational factors (such as occupation
      type, working hours per week, duration of the preoperative absence from work),
      psychological factors (such as a patient's concern about adverse health effects
      of RTW, feeling depressed, a patient's attitude towards his/her ability to RTW
      and a patient's perception of his/her job stress level) and medical factors (such
      as serum troponin T and creatine kinase MB (CKMB) level, pump time in surgery, co
      surgery and dyslipidemia history) had a statistically significant correlation
      with early return to work. The patients who early returned to work had
      significantly higher scores in 3 domains on the SF-36 questionnaire (used for
      assessing the patients' quality of life), compared to those who did not return to
      work early (including physical functioning, role limitations due to physical
      health and pain). CONCLUSIONS: In the present study we identified 4 new medical
      factors that could be used as predictors of early return to work after CABG.
      These factors are: normal serum troponin T level, shorter pump time in surgery,
      normal mean arterial pressure (MAP) before the surgery and higher serum magnesium
      (Mg) levels. Int J Occup Med Environ Health 2016;29(6):947-957.

PMID- 27869246
TI  - Multiple assessment methods of prenatal exposure to radio frequency radiation
      from telecommunication in the Mothers and Children's Environmental Health (MOCEH)
      study.
AB  - OBJECTIVES: To evaluate prenatal exposure to radiofrequency radiation (RFR) from
      telecommunication using a mobile phone questionnaire, operator data logs of
      mobile phone use and a personal exposure meter (PEM). MATERIAL AND METHODS: The
      study included 1228 mother-infants pairs from the Mothers and Children's
      Environmental Health (MOCEH) study - a multicenter prospective cohort study
      ongoing since 2006, in which participants were enrolled at <= 20 weeks of
      pregnancy, with a follow-up of a child birth and growth to assess the association
      between prenatal environmental exposure and children's health. The questionnaire
      included the average calling frequency per day and the average calling time per
      day. An EME Spy 100 PEM was used to measure RFR among 269 pregnant women from
      November 2007 to August 2010. The operators' log data were obtained from 21
      participants. The Spearman's correlation test was performed to evaluate
      correlation coefficient and 95% confidence intervals between the mobile phone use
      information from the questionnaire, operators' log data, and data recorded by the
      PEM. RESULTS: The operators' log data and information from the self-reported
      questionnaire showed significantly high correlations in the average calling
      frequency per day (rho = 0.6, p = 0.004) and average calling time per day (rho =
      0.5, p = 0.02). The correlation between information on the mobile phone use in
      the self-reported questionnaire and exposure index recorded by the PEM was poor.
      But correlation between the information of the operators' log data and exposure
      index for transmission of mobile communication was significantly high:
      correlation coefficient (p-value) was 0.44 (0.07) for calling frequency per day,
      and it was 0.49 (0.04) for calling time per day. CONCLUSIONS: The questionnaire
      information on the mobile phone use showed moderate to high quality. Using
      multiple methods for exposure assessment might be better than using only one
      method. Int J Occup Med Environ Health 2016;29(6):959-972.

PMID- 27869247
TI  - Effort-reward imbalance, overcommitment and their associations with all-cause and
      mental disorder long-term sick leave - A case-control study of the Swedish
      working population.
AB  - OBJECTIVES: To investigate if effort-reward imbalance (ERI) and overcommitment
      (OC) are associated with all-cause and mental disorder long-term sick leave (LS),
      and to identify differences in associations between genders, private versus
      public sector employees and socioeconomic status groups. MATERIAL AND METHODS:
      The study uses a cross-sectional case-control design with a sample of 3477
      persons on long-term sick leave of more than 59 days and a control group of 2078
      in employment. Data on sick leave originate from social insurance registers,
      while data on health, working and living conditions were gathered through a
      survey. The binary logistic regression was used to test the multivariate
      associations. RESULTS: Effort-reward imbalance was associated with all-cause LS
      among the women (odds ratio (OR) = 1.58, 95% CI: 1.2-2.08), but not among the
      men. Associations for mental disorder LS were evident for both ERI and OC among
      both genders (ERI/OC: women OR = 2.76/2.82; men OR = 2.18/2.92). For the men
      these associations were driven by high effort, while for the women it was low job
      esteem in public sector and low job security in private sector. Among the highly
      educated women, ERI was strongly related to mental disorder LS (OR = 6.94, 95%
      CI: 3.2-15.04), while the highly educated men seemed to be strongly affected by
      OC for the same outcome (OR = 5.79, 95% CI: 1.48-22.57). CONCLUSIONS: The study
      confirmed the independent roles of ERI and OC for LS, with stronger associations
      among the women and for mental disorders. The ERI model is a promising tool that
      can contribute to understanding the prevailing gender gap in sick leave and
      increasing sick leave due to mental disorders. Int J Occup Med Environ Health
      2016;29(6):973-989.

PMID- 27869248
TI  - Simplified risk assessment of noise induced hearing loss by means of 2
      spreadsheet models.
AB  - OBJECTIVES: The objective of this study has been to test 2 spreadsheet models to
      compare the observed with the expected hearing loss for a Norwegian reference
      population. MATERIAL AND METHODS: The prevalence rates of the Norwegian and the
      National Institute for Occupational Safety and Health (NIOSH) definitions of
      hearing outcomes were calculated in terms of sex and age, 20-64 years old, for a
      screened (with no occupational noise exposure) (N = 18 858) and unscreened (N =
      38 333) Norwegian reference population from the Nord-Trondelag Hearing Loss Study
      (NTHLS). Based on the prevalence rates, 2 different spreadsheet models were
      constructed in order to compare the prevalence rates of various groups of workers
      with the expected rates. The spreadsheets were then tested on 10 different
      occupational groups with varying degrees of hearing loss as compared to a
      reference population. RESULTS: Hearing of office workers, train drivers,
      conductors and teachers differed little from the screened reference values based
      on the Norwegian and the NIOSH criterion. The construction workers, miners,
      farmers and military had an impaired hearing and railway maintenance workers and
      bus drivers had a mildly impaired hearing. The spreadsheet models give a valid
      assessment of the hearing loss. CONCLUSIONS: The use of spreadsheet models to
      compare hearing in occupational groups with that of a reference population is a
      simple and quick method. The results are in line with comparable hearing
      thresholds, and allow for significance testing. The method is believed to be
      useful for occupational health services in the assessment of risk of noise
      induced hearing loss (NIHL) and the preventive potential in groups of noise
      exposed workers. Int J Occup Med Environ Health 2016;29(6):991-999.

PMID- 27869250
TI  - Preliminary analyses of psychometric characteristics of the Polish version of the
      Obsessive-Compulsive Inventory-Revised (OCI-R) in a non-clinical sample.
AB  - OBJECTIVES: Obsessive-compulsive disorder (OCD) is an anxiety-spectrum disorder
      that affects 1-2% of the adult population. People with OCD are more likely to
      report impaired social and occupational functioning. Although effective
      treatments of the OCD exist, many sufferers from this disorder are continuously
      misdiagnosed. Therefore, improving the assessment of the OCD remains an important
      area of scientific research. The main goal of the study is the initial
      verification of psychometric properties in the Polish version of the Obsessive
      Compulsive Inventory-Revised (OCI-R) in a college student sample. MATERIAL AND
      METHODS: A group of students completed a battery of measures consisting of
      obsessive-compulsive symptoms (The OCI-R, The Yale-Brown Obsessive Compulsive
      Scale), depression (The Beck Depression Inventory) and anxiety trait (The State
      Trait Anxiety Inventory). RESULTS: A confirmatory factor analysis, conducted on
      data from 334 university students, supported a solid and replicable 6-fold factor
      structure of the OCI-R. Further analyses on test-retest reliability (following a
      1-month interval), convergent and divergent validity of the OCI-R were
      respectively conducted in a group of 137 students who had completed a battery of
      measures mentioned above. The results showed adequate testretest reliability for
      the full scale and subscales cores, high internal consistency and confirmed
      satisfactory convergent and divergent validity. CONCLUSIONS: The study
      constitutes the first phase of work on a Polish version of measurement for
      obsessive-compulsive symptoms. Satisfactory results obtained in a non-clinical
      sample allow to recognize this method to be promising for further research. Int J
      Occup Med Environ Health 2016;29(6):1011-1021.

PMID- 27869249
TI  - A case-crossover study of sleep, fatigue, and other transient exposures at
      workplace and the risk of non-fatal occupational injuries among the employees of
      an Italian academic hospital.
AB  - OBJECTIVES: Transient exposure with acute effect has been shown to affect the
      risk of occupational injuries in various industrial settings and at the
      healthcare workplace. The objective of this study has been to identify transient
      exposures related to occupational injury risk in an Italian teaching hospital.
      MATERIAL AND METHODS: A case-crossover study was conducted among the employees of
      the University Hospital of Udine who reported an occupational injury, commuting
      accident, or incident involving biological risk in a 15-month period in the years
      2013 and 2014. The matched-pair interval approach was used to assess the role of
      acute sleep deprivation whereas the usual frequency approach was used for other
      13 transient exposures. RESULTS: Sleep hours were not associated with the risk of
      injuries whereas a significant risk increase was associated with fatigue, rush,
      distraction, emergency situations, teaching to or being taught by someone, non
      compliant patients, bloody operative/work field, excess noise, complex
      procedures, and anger. CONCLUSIONS: We identified transient exposures that
      increased the risk of occupational injuries in an Italian teaching hospital,
      providing indications for interventions to increase workers' safety at the
      healthcare workplace. Int J Occup Med Environ Health 2016;29(6):1001-1009.

PMID- 27869251
TI  - An Increased Genotoxic Risk in Lymphocytes from Phototherapy-Treated
      Hyperbilirubinemic Neonates.
AB  - BACKGROUND: Phototherapy is believed to be a safe method for the management of
      hyperbilirubinemia. However, there are some controversial issues regarding the
      genotoxic effects of phototherapy on DNA. The aim of this study was to
      investigate morphologically both phototherapy-induced DNA double-strand breaks
      (DSBs) and apoptosis in lymphocytes derived from jaundiced and non-jaundiced
      neonates. METHODS: Newborns were divided into three groups, including
      phototherapy-treated (PT, n=30) jaundiced newborns with total serum bilirubin
      (TSB) levels >15 mg/dl, non-treated jaundiced newborns (C+, n=27), as positive,
      as well as healthy negative (C-, n=30) controls with TSB levels ranging from 10
      and 15 mg/dl and less than 5 mg/dl, respectively. Lymphocytes were isolated from
      whole blood samples by Ficoll-isopaque density gradient centrifugation and then
      assessed for DNA damage and apoptosis before and 24 hours after incubation at 37
      degrees C in 5% CO2 using the neutral comet assay. RESULTS: DSB levels were
      significantly much higher in the PT group compared to the controls before
      incubation but decreased remarkably after the incubation period. As expected, no
      statistical differences were found between the two control groups before and
      after incubations. The frequency of apoptotic cells showed no significant
      differences among all the three groups before incubation; however, it was
      significantly increased in the PT group after incubation. CONCLUSION: It seems
      that phototherapy in jaundiced infants is able not only to induce apoptosis in
      newborn lymphocytes but also to affect indirectly DNA integrity.

PMID- 27869253
TI  - Long-term stable stacked CsPbBr3 quantum dot films for highly efficient white
      light generation in LEDs.
AB  - We report highly efficient ethyl cellulose with CsPbBr3 perovskite QD films for
      white light generation in LED application. Ethyl cellulose with CsPbBr3 quantum
      dots is applied with Sr2Si5N8 : Eu2+ red phosphor on an InGaN blue chip,
      achieving a highly efficient luminous efficacy of 67.93 lm W-1 under 20 mA
      current.

PMID- 27869254
TI  - Electronic structure of the germanium phosphide monolayer and Li-diffusion in its
      bilayer.
AB  - Based on the first-principles calculations, we predict that the monoclinic GeP
      can be exfoliated into two-dimensional (2D) monolayers. In fact, the interlayer
      van der Waals interactions are found to be comparable to those in black
      phosphorus. For the first time, we also elaborate mechanical and electronic
      properties of the monolayer for possible applications in optoelectronics.
      Although the monolayer is an indirect-gap semiconductor, it turns into a direct
      gap material under appropriate strain. Namely, the material exhibits a direct gap
      of 2.27 eV under 2% in-plane contraction along the softer (=a) axis. In addition,
      the contraction brings about an appreciable decrease in the effective mass of
      electrons along the b direction. The monolayer also practically turns into a
      direct-gap material under 4% tensile strain along the b direction. These results
      are particularly interesting, because our calculation indicates that the
      monolayer is about four times softer than graphene. Based on the calculation of
      activation barriers for various possible paths, we also identify anisotropic Li
      diffusion paths on the GeP monolayer as well as in the interlayer region of its
      bilayer. In the interlayer region, four parallel paths are identified along the b
      direction, where a Li atom can diffuse ~50 times faster than in the graphene
      bilayer. Our detailed calculations suggest that GeP can be also useful as an
      anode material in lithium ion batteries.

PMID- 27869252
TI  - Resin-dentin Bond Stability of Experimental 4-META-based Etch-and-rinse Adhesives
      Solvated by Ethanol or Acetone.
AB  - PURPOSE: To investigate the influence of 4-META concentration and type of solvent
      on the degree of conversion (DC%) and resin-dentin bond stability of experimental
      etch-and-rinse adhesives. MATERIALS AND METHODS: Four different concentrations of
      4-META (12 wt%, 20 wt%, 30 wt%, 40 wt%) were added to a model adhesive system
      consisting of TEG-DMA (25 wt%), UDMA (20 wt%), HEMA (30 wt%), water (4 wt%),
      camphorquinone (0.5 wt%), and tertiary amine (0.5 wt%) dissolved in 20% acetone
      (A12, A20, A30 and A40) or 20% ethanol (E12, E20, E30 and E40). DC% was evaluated
      by FT-IR spectroscopy. Human molars were wet ground until the occlusal dentin was
      exposed, the adhesive systems were applied after 37% phosphoric acid etching, and
      resin composite buildups were incrementally constructed. After storage in
      distilled water at 37 degrees C for 24 h, the teeth were cut into resin-dentin
      beams (cross-sectional area 1 mm2). Microtensile bond strength (MUTBS) was
      evaluated after 24 h, 6 months, and 1 year of water storage at 37 degrees C. The
      failure mode was categorized as adhesive, mixed, or cohesive. Data were analyzed
      using ANOVA and Tukey's HSD test (alpha = 0.05). RESULTS: A12 presented the
      lowest DC% (p < 0.05). All the other adhesive systems showed statistically
      similar DC% (p > 0.05). All adhesive systems maintained resin-dentin bond
      stability after 6 months of water storage, while only A40 and E40 maintained it
      after 1 year. CONCLUSION: Irrespective of the type of organic solvent, the
      incorporation of high concentrations of 4-META (40 wt%) improved the resin-dentin
      bond stability of the experimental etch-and-rinse adhesive systems over a period
      of 1 year.

PMID- 27869255
TI  - Metal-catalyzed C-H functionalization involving isocyanides.
AB  - Isocyanides have a broad range of applications in multicomponent reactions such
      as Passerini and Ugi processes. Recent advances in metal catalysis have
      tremendously increased the versatility of isocyanides in organic chemistry.
      Suitable metal catalysts could selectively activate various C-H bonds to allow
      direct functionalization under mild conditions, which represents a chemical
      process with broad synthetic potential. The synergy from the combination of
      isocyanide insertion and C-H bond activation offers an efficient and powerful
      tool to establish complicated reactions and to construct useful substances, from
      which the high potential of such strategy has been convincingly demonstrated in
      drug discovery, organic synthesis, and materials science. The present review
      highlights the most recent advances of isocyanide chemistry in metal-catalyzed C
      H bond functionalization.

PMID- 27869256
TI  - Two new phases of monolayer group-IV monochalcogenides and their piezoelectric
      properties.
AB  - Two stable structural phases of the monolayer group-IV monochalcogenides GeS,
      GeSe, SnS and SnSe have been found using first-principles calculations, and will
      be called as A-MX and H-MX. It is found that these two new phases are
      energetically nearly degenerate with the pristine phase Z-MX and are
      semiconductors for all four group-IV monochalcogenides. The band gaps of A-MX
      range from 1.62 eV to 1.86 eV, while H-MX exhibits wider band gaps in the range
      from 2.21 eV to 2.47 eV. Moreover, both of them exhibit significant piezoelectric
      properties. The piezoelectric coefficient of A-MX is about 1-2 orders of
      magnitude higher than those of other frequently used piezoelectric materials,
      showing obvious anisotropic characters, while that of H-MX is isotropic and
      comparable with those of other piezoelectric materials.

PMID- 27869257
TI  - Scaling relationships for nonadiabatic energy relaxation times in warm dense
      matter: toward understanding the equation of state.
AB  - Understanding the dynamics of electron-ion energy transfer in warm dense (WD)
      matter is important to the measurement of equation of state (EOS) properties and
      for understanding the energy balance in dynamic simulations. In this work, we
      present a comprehensive investigation of nonadiabatic electron relaxation and
      thermal excitation dynamics in aluminum under high pressure and temperature.
      Using quantum-classical trajectory surface hopping approaches, we examine the
      role of nonadiabatic couplings and electronic decoherence in electron-nuclear
      energy transfer in WD aluminum. The computed timescales range from 400 fs to 4.0
      ps and are consistent with existing experimental studies. We have derived general
      scaling relationships between macroscopic parameters of WD systems such as
      temperature or mass density and the timescales of energy redistribution between
      quantum and classical degrees of freedom. The scaling laws are supported by
      computational results. We show that electronic decoherence plays essential role
      and can change the functional dependencies qualitatively. The established scaling
      relationships can be of use in modelling of WD matter.

PMID- 27869258
TI  - Oxygen vacancy promoted methane partial oxidation over iron oxide oxygen carriers
      in the chemical looping process.
AB  - We perform ab initio DFT+U calculations and experimental studies of the partial
      oxidation of methane to syngas on iron oxide oxygen carriers to elucidate the
      role of oxygen vacancies in oxygen carrier reactivity. In particular, we explore
      the effect of oxygen vacancy concentration on sequential processes of methane
      dehydrogenation, and oxidation with lattice oxygen. We find that when CH4 adsorbs
      onto Fe atop sites without neighboring oxygen vacancies, it dehydrogenates with
      CHx radicals remaining on the same site and evolves into CO2via the complete
      oxidation pathway. In the presence of oxygen vacancies, on the other hand, the
      formed methyl (CH3) prefers to migrate onto the vacancy site while the H from CH4
      dehydrogenation remains on the original Fe atop site, and evolves into CO via the
      partial oxidation pathway. The oxygen vacancies created in the oxidation process
      can be healed by lattice oxygen diffusion from the subsurface to the surface
      vacancy sites, and it is found that the outward diffusion of lattice oxygen atoms
      is more favorable than the horizontal diffusion on the same layer. Based on the
      proposed mechanism and energy profile, we identify the rate-limiting steps of the
      partial oxidation and complete oxidation pathways. Also, we find that increasing
      the oxygen vacancy concentration not only lowers the barriers of CH4
      dehydrogenation but also the cleavage energy of Fe-C bonds. However, the barrier
      of the rate-limiting step cannot further decrease when the oxygen vacancy
      concentration reaches 2.5%. The fundamental insight into the oxygen vacancy
      effect on CH4 oxidation with iron oxide oxygen carriers can help guide the design
      and development of more efficient oxygen carriers and CLPO processes.

PMID- 27869259
TI  - The effect of top-layer chemistry on the formation of supported lipid bilayers on
      polyelectrolyte multilayers: primary versus quaternary amines.
AB  - The influence of the surface chemistry of polyelectrolyte multilayers (PEMs) on
      the formation of lipid bilayers is studied here for PEMs with either
      polyallylamine hydrochloride (PAH) or polydiallyldimethylammonium chloride
      (PDADMAC) as a polycation as a top layer, and polystyrene sulfonate (PSS) as a
      polyanion. Small unilamellar vesicles (SUVs) composed of phosphatidyl choline and
      phosphatidyl serine at a 50 : 50 molar ratio are deposited on top of the PEM
      films. The assembly of the SUVs into bilayers is studied via a quartz crystal
      microbalance with dissipation (QCM-D) and fluorescence recovery after
      photobleaching (FRAP). SUV deposition on PDADMAC/PSS results in vesicle
      adsorption while on PAH/PSS under the same conditions a bilayer is formed mainly
      due to weak interactions between the quaternary amines of PDADMAC. FRAP
      measurements confirm that SUVs are not fused on top of PDADMAC/PSS. The effect of
      phosphate ions, in solution, on the formation of lipid bilayers is also analysed.
      X-ray photoelectron spectroscopy shows the complexation of phosphate salts to the
      primary amines of PAH and no interaction with the quaternary amines of PDADMAC.
      zeta-potential measurements show a potential close to 0 for the PAH/PSS
      multilayers in PBS while PDADMAC/PSS displays a potential of 25 mV. A model is
      presented for the formation of lipid bilayers on PAH/PSS PEMs taking into account
      the role of phosphate ions in decreasing the electrostatic interactions between
      SUVs and PEMs and the formation of hydrogen bonds between the phospholipids and
      the primary amines of PAH.

PMID- 27869261
TI  - Choosing the right precursor for thermal decomposition solution-phase synthesis
      of iron nanoparticles: tunable dissociation energies of ferrocene derivatives.
AB  - Organometallic coordination compounds in general and metallocenes in particular
      are convenient precursors for the synthesis of metal nanoparticles through
      thermal decomposition. The strength of the interaction between the metal ion and
      its ligands determines the conditions under which decomposition occurs, most
      importantly the range of temperatures and pressures at which a given compound is
      useful as a precursor. We show that a comprehensive analysis of all individual
      contributions to the ligand metal interactions that establishes the nature of the
      interaction can be used to select compounds that are tuned to a specific
      dissociation energy with advantageous properties under experimental conditions.
      To this end, we apply the Morokuma-Ziegler-Energy Decomposition Analysis (MZ-EDA)
      to a series of ferrocene analogues using high-level density functional theory
      (DFT). We find that asymmetrically substituted ferrocene derivatives are unlikely
      to be useful as precursors because of the large energy required to remove the
      second cyclopentadienyl-derivative from the central iron atom. However, we are
      able to establish that symmetrically substituted chloroferrocenes exhibit a wide
      range of relatively low bond dissociation energies for both dissociation steps
      and are hence good candidates for the synthesis of highly mono-disperse iron
      nanoparticles.

PMID- 27869260
TI  - Thermally induced phase separation in levitated polymer droplets.
AB  - We report thermally induced rapid phase separation in PS/PVME polymer blends
      using a unique contact free droplet based architecture. De-mixing of homogeneous
      blends due to inter component dynamic asymmetry is aggravated by the externally
      supplied heat. Separation of polymer blends is usually investigated in the bulk
      which is a tedious process and requires several hours for completion.
      Alternatively, separation in droplet configuration reduces the process timescale
      by about 3-5 orders due to a constrained micron-sized domain [fast processing and
      high throughput] while maintaining similar separation morphologies as in the
      bulk. We observed the effect of heating rates on the phase separation length and
      timescales. Furthermore, the separation length scale can be precisely controlled
      across one order by simply tuning the heating rate. The methodology can be scaled
      up for applications ranging from surface patterning to pharmaceutics.

PMID- 27869262
TI  - Statistical thermodynamics of aromatic-aromatic interactions in aqueous solution.
AB  - To elucidate the interactions between aromatic rings, which are believed to play
      essential roles in a variety of biological processes, we analyze the water
      mediated interactions between toluene molecules along face-to-face stacked (FF)
      and point-to-face T-shaped (TS) paths using a statistical-mechanical theory of
      liquids combined with a molecular model for water. The theory enables us to
      decompose each interaction into physically insightful components, revealing
      detailed hydration effects. The dimers (i.e., molecules in contact with each
      other) formed in the FF and TS paths, which are referred to as "FF stacking" and
      "TS contact", respectively, share almost the same stability in vacuum. In water,
      however, the stability of the FF stacking increases whereas that of the TS
      contact decreases. By the energetic hydration effect, for the FF stacking, more
      than half of the London dispersion attractive interaction is cancelled out and
      the electrostatic repulsive interaction is significantly screened. Importantly, a
      large gain of water entropy occurs. For the TS contact, the London dispersion
      interaction is almost completely cancelled out and the electrostatic component of
      the water-mediated interaction becomes repulsive. It is accompanied by a water
      entropy gain. The water-entropy effect is crucially important for the
      participation of aromatic side chains in the close packing of a protein as well
      as FF stacked arrangements of aromatic rings in the case of nucleotide base
      interactions. The term "pi-pi stacking" is inappropriate for the stacking in
      aqueous solution, because it sounds as if the London dispersion interaction was
      the only contributor to it as in vacuum.

PMID- 27869263
TI  - Combined electronic and thermodynamic approaches for enhancing the thermoelectric
      properties of Ti-doped PbTe.
AB  - Lead telluride based compounds are of great interest due to their enhanced
      thermoelectric transport properties. Nevertheless, the donor type impurities in
      this class of materials are currently mainly limited and alternative types of
      donor impurities are still required for optimizing the thermoelectric
      performance. In the current research titanium as a donor impurity in PbTe is
      examined. Although titanium is known to form resonant levels above the conduction
      band in PbTe, it does not enhance the thermo-power beyond the classical
      predictions. Recent experiments showed that alloying with a small amount of Ti
      (~0.1 at%) gives a significant increase in the figure of merit. In the current
      research ab initio calculations were applied in order to correlate the reported
      experimental results with a thermoelectric optimization model. It was found that
      a Ti concentration of ~1.4 at% in the Pb sublattice is expected to maximize the
      thermoelectric power factor. Using a statistical thermodynamic approach and in
      agreement with the previously reported appearance of a secondary intermetallic
      phase, the actual Ti solubility limit in PbTe is found to be ~0.3 at%. Based on
      the proposed model, the mechanism for the formation of the previously observed
      secondary phase is attributed to phase separation reactions, characterized by a
      positive enthalpy of formation in the system. With extrapolation of the obtained
      ab initio results, it is demonstrated that lower Ti-doping concentrations than
      previously experimentally reported ones are expected to provide power factor
      values close to the maximal one, making doping with Ti a promising opportunity
      for the generation of highly efficient n-type PbTe-based thermoelectric
      materials.

PMID- 27869264
TI  - X-ray emission spectroscopy: highly sensitive techniques for time-resolved
      probing of cerium reactivity under catalytic conditions.
AB  - Oxygen storage materials such as ceria are used in many catalytic applications
      because they can reversibly bind and release oxygen. Tools are needed to observe
      and quantify this activity which involves a change in the cerium oxidation state
      and to understand the involvement of cerium in catalytic processes. To prove that
      cerium changes its oxidation state in the catalytic cycle the transient rates of
      Ce3+ formation and decay should be compared to the overall reaction rate. For
      such mechanistic studies the time resolution is essential as the quantification
      of the Ce3+ species should be faster than the reaction rate. However, it is
      challenging to follow the dynamic changes of the cerium oxidation state under
      reaction conditions, especially when the concentration of cerium atoms involved
      in the reaction cycle is low. In this paper, we evaluate the sensitivity of high
      resolution X-ray emission-based methods for the in situ time-resolved
      quantification of small concentrations of Ce3+ in ceria-based materials. We
      demonstrate that resonant X-ray emission spectroscopy (RXES) at optimal
      excitation energy is more sensitive than high energy resolution off-resonant
      spectroscopy (HEROS) and non-resonant X-ray emission spectroscopy (non-resonant
      XES) and that it can track the reactivity of less than 0.3% of cerium atoms in a
      1% Pt/CeO2 catalyst in a plug-flow reactor with sub-second time resolution. These
      results demonstrate that X-ray emission-based methods can be used as very
      sensitive tools and provide new insights into dynamic changes of the oxidation
      state in reducible oxides in a variety of applications.

PMID- 27869265
TI  - Radiation-induced transformations of methanol molecules in low-temperature
      solids: a matrix isolation study.
AB  - The effect of X-ray irradiation on methanol molecules (CH3OH, CD3OH, and 13CH3OH)
      isolated in solid noble gas matrices (Ne, Ar, Kr, and Xe) was studied by FTIR
      spectroscopy at 6 K. CH2OH, H2CO, HCO and CO were found to be the main
      degradation products. Somewhat unexpectedly, the production of CO is quite
      prominent, even at low doses, and it strongly predominates in low-polarizable
      matrices (especially, in neon). This result is explained by inefficient quenching
      of excess energy in the H2CO molecules initially generated from methanol.
      Relatively small amounts of CH4, CH3 and CO2 were also observed directly after
      irradiation. The latter species presumably originates from methanol dimers or
      methanol-water complexes. The mechanisms of radiolysis and annealing-induced
      reactions are discussed and possible implications for the astrochemically
      relevant ices are considered.

PMID- 27869266
TI  - Fluorescent carbon nanoparticles: mimicking hydrogen peroxide properties in a
      chemiluminescence system.
AB  - Fluorescent carbon nanoparticles (FCNs), as novel luminescent reagents exhibiting
      hydrogen peroxide mimicking properties, can directly react with luminol, NaHCO3
      and NaHSO3 in alkaline conditions to yield novel chemiluminescence, and show
      great potential towards further applications of ultra-weak chemiluminescence.

PMID- 27869267
TI  - The reaction mechanism of polyalcohol dehydration in hot pressurized water.
AB  - The use of high-temperature liquid water (HTW) as a reaction medium is a very
      promising technology in the field of green chemistry. In order to fully exploit
      this technology, it is crucial to unravel the reaction mechanisms of the
      processes carried out in HTW. In this work, the reaction mechanism of 2,5
      hexanediol dehydration in HTW has been studied by means of three different ab
      initio simulations: the string method, metadynamics and molecular dynamics in
      real time. It is found that the whole reaction involving protonation, bond
      exchange and deprotonation occurs in a single step without a stable intermediate.
      The hydrogen bonded network of the surrounding water has a vital role in
      assisting an efficient proton relay at the beginning and at the end of the
      reaction. It is confirmed that the reaction is energetically most favorable in
      the SN2 pathway with an estimated barrier of 36 kcal mol-1, which explains the
      high stereoselectivity and the reaction rate observed in experiment. The
      mechanistic insights provided by our study are relevant for a prominent class of
      reactions in the context of sustainable biomass processing, namely dehydration
      reactions of polyalcohol molecules.

PMID- 27869269
TI  - In situ phase behaviour of a high capacity LiCoPO4 electrode during constant or
      pulsed charge of a lithium cell.
AB  - The phase changes that occur during lithium extraction from LiCoPO4 in lithium
      half-cells were studied using synchrotron X-ray diffraction. The existence of two
      two-phase regions with an intermediate phase present was observed. Significant
      variations in the composition of the phases of nominal stoichiometry LiCoPO4,
      Li2/3CoPO4 and CoPO4 resulted in unit cell volume variations. On current pulsing,
      lattice parameter shifts and phase recovery were directly observed.

PMID- 27869270
TI  - Triplex-forming PNA modified with unnatural nucleobases: the role of protonation
      entropy in RNA binding.
AB  - Peptide nucleic acid (PNA) modified with unnatural nucleobases enables the
      formation of a highly stable triplex with a double-stranded RNA at physiological
      pH. In this communication, we evaluated kinetics and thermodynamics of PNA/RNA
      triplex formation as a function of both pH and temperature. Protonation entropy
      was found to be the major factor responsible for the destabilization of the
      triplex and for the progressive decrease in the association rate at more basic
      pHs.

PMID- 27869268
TI  - Self-assembling nanowires of an amphiphilic camptothecin prodrug derived from
      homologous derivative conjugation.
AB  - A novel amphiphilic camptothecin prodrug, CPT-ss-Ir, consisting of CPT, Ir and a
      disulfide bond linker, was synthesized, and it could self-assemble into nanowires
      in aqueous solution. Upon intracellular triggering, active CPT and Ir species
      were released to exert a considerable anticancer effect.

PMID- 27869272
TI  - Tetracyclic dihydronaphthalene derivatives via gold-catalyzed aminative
      homodimerization of ortho-alkynylbenzaldehydes.
AB  - Gold(i) catalyzes domino homodimerization of o-alkynylbenzaldehydes via a
      sequence of 6-endo-dig-cyclization, amine addition, and [4+2] cycloaddition
      involving two bicyclic intermediates. The resulting products integrate
      medicinally relevant 1,2-dihydronaphthalene and isochromene moieties into a
      single amine-substituted tetracyclic framework.

PMID- 27869271
TI  - Effects of strong interactions between Ti and ceria on the structures of Ti/CeO2.
AB  - The effects of strong interactions between Ti and ceria on the structures of
      Ti/CeO2(111) are systematically investigated by density functional theory
      calculation. To our best knowledge, the adsorption energy of a Ti atom at the
      hollow site of CeO2 is the highest value (-7.99 eV) reported in the literature
      compared with those of Au (-0.88--1.26 eV), Ag (-1.42 eV), Cu (-2.69 eV), Pd (
      1.75 eV), Pt (-2.62 eV) and Sn (-3.68 eV). It is very interesting to find that Ti
      adatoms disperse at the hollow site of CeO2(111) to form surface TiOx species,
      instead of aggregating to form Ti metal clusters for the Ti-CeO2 interactions
      that are much stronger than those of Ti-Ti ones. Ti adatoms are completely
      oxidized to Ti4+ ions if they are monatomically dispersed on the next near hollow
      sites of CeO2(111) (xTi-NN-hollow); while Ti3+ ions are observed when they locate
      at the near hollow sites (xTi-N-hollow). Due to the electronic repulsive effects
      among Ti3+ ions, the adsorption energies of xTi-N-hollow are slightly weaker than
      those of xTi-NN-hollow. Simultaneously, the existence of unstable Ti3+ ions on
      xTi-N-hollow also leads to the restructuring of xTi-N-hollow by surface O atoms
      of ceria transferring to the top of Ti3+ ions, or oxidation by O2 adsorption and
      dissociation. Both processes improve the stability of the xTi/CeO2 system by Ti3+
      oxidation. Correspondingly, surface TiO2-like species form. This work sheds light
      into the structures of metal/CeO2 catalysts with strong interactions between the
      metal and the ceria support.

PMID- 27869273
TI  - An autonomic self-healing organogel with a photo-mediated modulus.
AB  - A new method is described for fabricating autonomic, self-healing, deformable
      organogels. We combined imidazolium-based poly(ionic liquid) (PIL) and azobenzene
      grafted poly(carboxylic acid) (PAA-Azo) in N,N-dimethyl formamide. Further,
      complexing PIL with unirradiated (trans) or irradiated (cis) PAA-Azo tuned the
      elastic modulus of the organogel.

PMID- 27869274
TI  - A platform for the development of novel biosensors by configuring allosteric
      transcription factor recognition with amplified luminescent proximity homogeneous
      assays.
AB  - A wide range of chemicals can be sensed by allosteric transcription factors
      (aTFs) in bacteria. Herein, we report a biosensing platform by using isolated
      aTFs as recognition elements in vitro. Moreover, a general strategy to increase
      the sensitivity of the aTF-based biosensors is provided. As a proof-of-concept,
      we obtained by far the most sensitive uric acid and oxytetracycline biosensors by
      using aTF HucR and OtrR as recognition elements, respectively. As a large number
      of aTFs are present in bacteria, our work opens a novel route to develop
      sensitive aTF-based biosensors.

PMID- 27869275
TI  - Ratiometric and photoconvertible fluorescent protein-based voltage indicator
      prototypes.
AB  - To expand the toolbox of fluorescent protein-based voltage indicators, we
      explored two distinct protein design strategies. Using these design strategies,
      we created three new voltage indicators: a red intensiometric voltage indicator
      (tdFlicR Delta110AR), a green/red ratiometric voltage indicator (tdFlicR-VK
      ASAP), and a green to red photoconvertible voltage indicator (FlicGR1).

PMID- 27869277
TI  - A chemical proteomic probe for detecting native carrier protein motifs in
      nonribosomal peptide synthetases.
AB  - Derivatization of a 5'-(vinylsulfonylaminodeoxy)adenosine scaffold with a
      clickable functionality provided an activity-based probe that was used to label
      native carrier protein (CP) motifs in nonribosomal peptide synthetases (NRPSs).
      When coupled with a fluorescent tag, this probe selectively targeted
      phosphopantetheinylated CPs (holo-form) from recombinant NRPS enzyme systems and
      in whole proteomes.

PMID- 27869276
TI  - Molecular tweezers target a protein-protein interface and thereby modulate
      complex formation.
AB  - Molecular tweezers for lysine and arginine select a few residues on a protein
      surface and by their unique complexation mode disrupt a critical protein-protein
      interaction. Detailed structural information was gained by NMR experiments,
      strongly supported by QM/MM calculations and further substantiated by ITC,
      fluorescence anisotropy, ELISA and bio-layer-interference studies.

PMID- 27869278
TI  - Cellular delivery of enzyme-loaded DNA origami.
AB  - In this communication, we show that active enzymes can be delivered into HEK293
      cells in vitro when they are attached to tubular DNA origami nanostructures. We
      use bioluminescent enzymes as a cargo and monitor their activity from a cell
      lysate. The results show that the enzymes stay intact and retain their activity
      in the transfection process. The method is highly modular, which makes it a
      compelling candidate for a great variety of delivery applications.

PMID- 27869279
TI  - Highly potent extranuclear-targeted luminescent iridium(iii) antitumor agents
      containing benzimidazole-based ligands with a handle for functionalization.
AB  - A series of 6 substitutionally inert and luminescent iridium(iii) antitumor
      agents of the type [Ir(C?N)2(N?N)][PF6] containing a benzimidazole N?N ligand
      with an ester group as a handle for further functionalization has been prepared.
      They exhibit IC50 values in the high nanomolar range in some ovarian and breast
      cancer cell lines (approximately 100* more cytotoxic than cisplatin (CDDP) in MDA
      MB-231) and are located in the actin cortex predominantly as shown by confocal
      luminescence microscopy. This discovery could open the door to a new large family
      of drug bioconjugates with diverse and simultaneous functions.

PMID- 27869280
TI  - Self-assembly of a supramolecular network with pseudo-rotaxane cross-linking
      nodes and its transformation into a mechanically locked structure by rotaxane
      formation.
AB  - A main chain poly(crown ether) macromolecule has been cross-linked with a two
      binding site guest to afford a stimuli-responsive supramolecular polymeric
      network with pseudo-rotaxane nodes. This network forms gels and films that are
      responsive to temperature and solvent polarity; however, the materials can be
      shielded against both effects by transforming the pseudo-rotaxane junctions into
      rotaxane links, creating a mechanically locked structure.

PMID- 27869281
TI  - Solution self-assembly of plasmonic Janus nanoparticles.
AB  - Janus nanoparticles bearing two different properties on a single particle are
      amenable to self-assembly into higher-order structures via their directional
      interaction. We show that gold/silica Janus nanoparticles self-assemble in
      solution into clusters resembling colloidal micelles upon addition of a
      hydrophobic thiol which provides them with a surface active amphiphilic
      character. As the nanoparticles spontaneously assemble, the color of the solution
      evolves due to the coupling of the surface plasmons. Time resolved
      spectrophotometry in the visible and near-infrared ranges coupled to simulations
      were used to probe the assembly process. A singular value decomposition analysis
      reveals the presence of dimers as transient species. The structure of the
      clusters was probed using small angle X-ray revealing that the Janus
      nanoparticles assemble into clusters containing a few particles.

PMID- 27869282
TI  - Adsorption and desorption behavior of ionic and nonionic surfactants on polymer
      surfaces.
AB  - We report combined experimental and computational studies aiming to elucidate the
      adsorption properties of ionic and nonionic surfactants on hydrophobic polymer
      surface such as poly(styrene). To represent these two types of surfactants, we
      choose sodium dodecyl sulfate and poly(ethylene glycol)-poly(ethylene) block
      copolymers, both commonly utilized in emulsion polymerization. By applying quartz
      crystal microbalance with dissipation monitoring we find that the non-ionic
      surfactants are desorbed from the poly(styrene) surface slower, and at low
      surfactant concentrations they adsorb with stronger energy, than the ionic
      surfactant. If fact, from molecular dynamics simulations we obtain that the
      effective attractive force of these nonionic surfactants to the surface increases
      with the decrease of their concentration, whereas, the ionic surfactant exhibits
      mildly the opposite trend. We argue that the difference in this contrasting
      behavior stems from the physico-chemical properties of the head group. Ionic
      surfactants characterized by small and strongly hydrophilic head groups form an
      ordered self-assembled structure at the interface whereas, non-ionic surfactants
      with long and weakly hydrophilic head groups, which are also characterized by low
      persistence lengths, generate a disordered layer. Consequently, upon an increase
      in concentration, the layer formed by the nonionic surfactants prevents the
      aprotic poly(ethylene glycol) head groups to satisfy all their hydrogen bonds
      capabilities. As a response, water molecules intrude this surfactant layer and
      partially compensate for the missing interactions, however, at the expense of
      their ability to form hydrogen bonds as in bulk. This loss of hydrogen bonds,
      either of the head groups or of the intruding water molecules, is the reason the
      nonionic surfactants weaken their effective attraction to the interface with the
      increase in concentration.

PMID- 27869283
TI  - Controlling the electrical conductive network formation of polymer nanocomposites
      via polymer functionalization.
AB  - By adopting coarse-grained molecular dynamics simulations, the effect of polymer
      functionalization on the relationship between the microstructure and the electric
      percolation probability of nanorod filled polymer nanocomposites has been
      investigated. At a low chain functionalization degree, the nanorods in the
      polymer matrix form isolated aggregates with a local order structure. At a
      moderate chain functionalization degree, the local order structure of the nanorod
      aggregate is gradually broken up. Meanwhile, excessive functionalization chain
      beads can connect the isolated aggregates together, which leads to the maximum
      size of nanorod aggregation. At a high chain functionalization degree, it forms a
      single nanorod structure in the matrix. As a result, the highest percolation
      probability of the materials appears at the moderate chain functionalization
      degree, which is attributed to the formation of the tightly connected nanorod
      network by analyzing the main cluster. In addition, this optimum chain
      functionalization degree exists at two chain functionalization modes (random and
      diblock). Lastly, under the tensile field, even though the contact distance
      between nanorods nearly remains unchanged, the topological structure of the
      percolation network is broken down. While under the shear field, the contact
      distance between nanorods increases and the topological structure of the
      percolation network is broken down, which leads to a decrease in the percolation
      probability. In total, the topological structure of the percolation network
      dominates the percolation probability, which is not a necessary connection with
      the contact distance between nanorods. In summary, this work presents further
      understanding of the electric conductive properties of nanorod-filled
      nanocomposites with functionalized polymers.

PMID- 27869284
TI  - Phase separation and coexistence of hydrodynamically interacting microswimmers.
AB  - A striking feature of the collective behavior of spherical microswimmers is that
      for sufficiently strong self-propulsion they phase-separate into a dense cluster
      coexisting with a low-density disordered surrounding. Extending our previous
      work, we use the squirmer as a model swimmer and the particle-based simulation
      method of multi-particle collision dynamics to explore the influence of
      hydrodynamics on their phase behavior in a quasi-two-dimensional geometry. The
      coarsening dynamics towards the phase-separated state is diffusive in an
      intermediate time regime followed by a final ballistic compactification of the
      dense cluster. We determine the binodal lines in a phase diagram of Peclet number
      versus density. Interestingly, the gas binodals are shifted to smaller densities
      for increasing mean density or dense-cluster size, which we explain using a
      recently introduced pressure balance [S. C. Takatori, et al., Phys. Rev. Lett.
      2014, 113, 028103] extended by a hydrodynamic contribution. Furthermore, we find
      that for pushers and pullers the binodal line is shifted to larger Peclet numbers
      compared to neutral squirmers. Finally, when lowering the Peclet number, the
      dense phase transforms from a hexagonal "solid" to a disordered "fluid" state.

PMID- 27869285
TI  - Discontinous change from thermally- to geometrically-dominated effective
      interactions in colloidal solutions.
AB  - We report numerical results for the effective potential arising between two
      colloids immersed in a self-assembling cosolute which forms reversible clusters.
      The potential is evaluated at cosolute state points with different densities and
      temperatures but with the same connectivity properties. We find that the range of
      the resulting effective potential is controlled only by the cosolute thermal
      correlation length rather than by its connectivity length. We discuss the
      significant differences from previous results focusing on the cosolute forming
      irreversible clusters and we show that the irreversible bond case represents a
      singular limit which cannot be accessed in equilibrium by continuously increasing
      the bond lifetime.

PMID- 27869286
TI  - Dynamic self-organization of side-propelling colloidal rods: experiments and
      simulations.
AB  - In recent years, there is a growing interest in designing artificial analogues of
      living systems, fueled not only by potential applications as 'smart micro
      machines', but also by the demand for simple models that can be used to study the
      behavior of their more complex natural counterparts. Here, we present a facile,
      internally driven, experimental system comprised of fluorescently labeled
      colloidal silica rods of which the self-propulsion is powered by the
      decomposition of H2O2 catalyzed by a length-wise half Pt coating of the particles
      in order to study how shape anisotropy and swimming direction affect the
      collective behavior. We investigated the emerging structures and their time
      evolution for various particle concentrations in (quasi-)two dimensional systems
      for three aspect ratios of the rods on a single particle level using a
      combination of experiments and simulations. We found that the dynamic self
      organization relied on a competition between self-propulsion and phoretic
      attractions induced by phoresis of the rods. We observed that the particle
      clustering behavior depends on the concentration as well as the aspect ratio of
      the rods. Our findings provide a more detailed understanding of dynamic self
      organization of anisotropic particles and the role the propulsion direction plays
      in internally driven systems.

PMID- 27869287
TI  - Dexmedetomidine for attenuating haemodynamic response to intubation stimuli in
      morbidly obese patients anaesthetised using low-opioid technique: comparison with
      fentanyl-based general anaesthesia.
AB  - BACKGROUND: Anaesthesiologists are facing the problem of an increasing population
      of morbidly obese patients. In order to minimize the risk of opioid-induced
      postoperative respiratory failure, the intraoperative administration of opioids
      should be reduced or replaced with other drugs. The purpose of this study was to
      compare haemodynamic response elicited by intubation in morbidly obese patients
      between two variants of anaesthesia induction: fentanylbased or low-opioid using
      dexmedetomidine. METHODS: Forty-two morbidly obese patients scheduled for
      bariatric surgery were randomly assigned to two groups: low-opioid using
      dexmedetomidine (DEX) or fentanyl-based (FNT) anaesthesia. Patients were
      premedicated with 100 MUg of fentanyl i.v. In the DEX group, a 10 minute infusion
      of a loading dose of 200 MUg of dexmedetomidine was started. In the FNT group, 2
      mg of intravenous midazolam was given. Thereafter, propofol was used in both
      groups. In the FNT group, patients received a dose of fentanyl up to 5 MUg kg-1
      of ideal body weight. Following administration of rocuronium, laryngoscopy and
      tracheal intubation were performed. Haemodynamic parameters, including systolic
      (SBP), diastolic (DBP) and mean arterial (MAP) blood pressure, as well as heart
      rate (HR), were recorded before and after intubation. Patients who were not
      intubated at first attempt were excluded from the study. RESULTS: Data from 33
      patients were analysed. There were no statistically significant differences
      between the DEX and FNT groups regarding demographic data. Haemodynamic response
      to intubation was defined as mean change (d) in values of analysed parameters
      that occurred during intubation. The following differences were observed: dSBP
      FNT +11.6 mm Hg vs. DEX +0.4 mm Hg (P = 0.15); dDBP FNT +3.7 mm Hg vs. DEX +3.5
      mm Hg (P = 0.98); dMAP FNT +8.6 mm Hg vs. DEX +1.4 mm Hg (P = 0.36); dHR FNT +2
      beats min-1 vs. DEX -1 beat min-1 (P = 0.30). None of these comparisons yielded
      significant differences. CONCLUSIONS: The study revealed no advantage of fentanyl
      over low opioid dexmedetomidine-based induction of general anaesthesia in
      attenuating cardiovascular response to intubation in morbidly obese patients.

PMID- 27869288
TI  - Infraclavicular access to the axillary vein - new possibilities for the
      catheterization of the central veins in the intensive care unit.
AB  - Central vein cannulation is one of the most commonly performed procedures in
      intensive care. Traditionally, the jugular and subclavian vein are recommended as
      the first choice option. Nevertheless, these attempts are not always obtainable
      for critically ill patients. For this reason, the axillary vein seems to be a
      rational alternative approach. In this narrative review, we evaluate the
      usefulness of the infraclavicular access to the axillary vein. The existing
      evidence suggests that infraclavicular approach to the axillary vein is a
      reliable method of central vein catheterization, especially when performed with
      ultrasound guidance.

PMID- 27869289
TI  - Integration of parallel 13 C-labeling experiments and in silico pathway analysis
      for enhanced production of ascomycin.
AB  - Herein, the hyper-producing strain for ascomycin was engineered based on 13 C
      labeling experiments and elementary flux modes analysis (EFMA). First, the
      metabolism of non-model organism Streptomyces hygroscopicus var. ascomyceticus
      SA68 was investigated and an updated network model was reconstructed using 13 C-
      metabolic flux analysis. Based on the precise model, EFMA was further employed to
      predict genetic targets for higher ascomycin production. Chorismatase (FkbO) and
      pyruvate carboxylase (Pyc) were predicted as the promising overexpression and
      deletion targets, respectively. The corresponding mutant TD-FkbO and TD-DeltaPyc
      exhibited the consistency effects between model prediction and experimental
      results. Finally, the combined genetic manipulations were performed, achieving a
      high-yield ascomycin engineering strain TD-DeltaPyc-FkbO with production up to
      610 mg/L, 84.8% improvement compared with the parent strain SA68. These results
      manifested that the integration of 13 C-labeling experiments and in silico
      pathway analysis could serve as a promising concept to enhance ascomycin
      production, as well as other valuable products. Biotechnol. Bioeng. 2017;114:
      1036-1044. (c) 2016 Wiley Periodicals, Inc.

PMID- 27869290
TI  - Developmental Differences in Infants' Fairness Expectations From 6 to 15 Months
      of Age.
AB  - The present research investigated the developmental trajectory of infants'
      fairness expectations from 6 to 15 months of age (N = 150). Findings revealed a
      developmental transition in infants' fairness expectations between 6 and 12
      months, as indicated by enhanced visual attention to unfair outcomes of resource
      distribution events (a 3:1 distribution) relative to fair outcomes (a 2:2
      distribution). The onset of naturalistic sharing behavior predicted infants'
      fairness expectations at transitional ages. Beyond this period of developmental
      transition, the presence of siblings and infants' prompted giving behavior
      predicted individual differences in infants' fairness concerns. These results
      provide evidence for the role of experience in the acquisition of fairness
      expectations and reveal early individual differences in such expectations.

PMID- 27869291
TI  - Managing Innovation to Maximize Value Along the Discovery-Translation-Application
      Continuum.
AB  - Success in pharmaceutical development led to a record 51 drugs approved in the
      past year, surpassing every previous year since 1950. Technology innovation
      enabled identification and exploitation of increasingly precise disease targets
      ensuring next generation diagnostic and therapeutic products for patient
      management. The expanding biopharmaceutical portfolio stands, however, in
      contradistinction to the unsustainable costs that reflect remarkable challenges
      of clinical development programs. This annual Therapeutic Innovations issue
      juxtaposes advances in translating molecular breakthroughs into transformative
      therapies with essential considerations for lowering attrition and improving the
      cost-effectiveness of the drug-development paradigm. Realizing the discovery
      translation-application continuum mandates a congruent approval, adoption, and
      access triad.

PMID- 27869292
TI  - Model-based investigation of intracellular processes determining antibody Fc
      glycosylation under mild hypothermia.
AB  - Despite the positive effects of mild hypothermic conditions on monoclonal
      antibody (mAb) productivity (qmAb ) during mammalian cell culture, the impact of
      reduced culture temperature on mAb Fc-glycosylation and the mechanism behind
      changes in the glycan composition are not fully established. The lack of
      knowledge about the regulation of dynamic intracellular processes under mild
      hypothermia restricts bioprocess optimization. To address this issue, a
      mathematical model that quantitatively describes Chinese hamster ovary (CHO) cell
      behavior and metabolism, mAb synthesis and mAb N-linked glycosylation profile
      before and after the induction of mild hypothermia is constructed. Results from
      this study show that the model is capable of representing experimental results
      well in all of the aspects mentioned above, including the N-linked glycosylation
      profile of mAb produced under mild hypothermia. Most importantly, comparison
      between model simulation results for different culture temperatures suggests the
      reduced rates of nucleotide sugar donor production and galactosyltransferase
      (GalT) expression to be critical contributing factors that determine the
      variation in Fc-glycan profiles between physiological and mild hypothermic
      conditions in stable CHO transfectants. This is then confirmed using experimental
      measurements of GalT expression levels, thereby closing the loop between the
      experimental and the computational system. The identification of bottlenecks
      within CHO cell metabolism under mild hypothermic conditions will aid bioprocess
      optimization, for example, by tailoring feeding strategies to improve NSD
      production, or manipulating the expression of specific glycosyltransferases
      through cell line engineering. Biotechnol. Bioeng. 2017;114: 1570-1582. (c) 2016
      The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals Inc.

PMID- 27869293
TI  - Addressing multilevel barriers to cervical cancer screening in Korean American
      women: A randomized trial of a community-based intervention.
AB  - BACKGROUND: Korean American women have among the lowest rates of cervical cancer
      screening in the United States. The authors evaluated a multicomponent
      intervention combining community education with navigation services to reduce
      access barriers and increase screening rates in this underserved population. It
      was hypothesized that cervical cancer screening rates would be higher among women
      who received the intervention program compared with those in the control program.
      METHODS: Korean American women (N = 705) were recruited from 22 churches. In this
      matched-pair, group-randomized design, 347 women received the intervention, which
      consisted of a culturally relevant cancer education program combined with
      provision of navigation services. The control group (N = 358) received general
      health education, including information about cervical cancer risk and screening
      and where to obtain low-cost or no-cost screening. Screening behavior was
      assessed 12 months after the program. RESULTS: Screening behavior data were
      obtained from 588 women 12 months after the program. In both site-level and
      participant-level analyses, the intervention program contributed to significantly
      higher screening rates compared with the control program (odds ratio [OR], 25.9;
      95% confidence interval [CI], 10.1-66.1; P < .001). In sensitivity analysis, the
      treatment effect remained highly significant (OR, 16.7; 95% CI, 8.1-34.4; P <
      .001). CONCLUSIONS: A multicomponent intervention combining community cancer
      education with navigation services yielded significant increases in cervical
      cancer screening rates among underscreened Korean American women. Community
      accessible programs that incorporate cancer education with the delivery of key
      navigation services can be highly effective in increasing cervical cancer
      screening rates in this underserved population. Cancer 2017;123:1018-26. (c) 2016
      American Cancer Society.

PMID- 27869294
TI  - Enhancement of human neural stem cell self-renewal in 3D hypoxic culture.
AB  - The pathology of neurological disorders is associated with the loss of neuronal
      and glial cells that results in functional impairments. Human neural stem cells
      (hNSCs), due to their self-renewing and multipotent characteristics, possess
      enormous tissue-specific regenerative potential. However, the efficacy of
      clinical applications is restricted due to the lack of standardized in vitro cell
      production methods with the capability of generating hNSC populations with well
      defined cellular compositions. At any point, a population of hNSCs may include
      undifferentiated stem cells, intermediate and terminally differentiated
      progenies, and dead cells. Due to the plasticity of hNSCs, environmental cues
      play crucial roles in determining the cellular composition of hNSC cultures over
      time. Here, we investigated the independent and synergistic effect of three
      important environmental factors (i.e., culture dimensionality, oxygen
      concentration, and growth factors) on the survival, renewal potential, and
      differentiation of hNSCs. Our experimental design included two dimensional (2D)
      versus three dimensional (3D) cultures and normoxic (21% O2 ) versus hypoxic (3%
      O2 ) conditions in the presence and absence of epidermal growth factor (EGF) and
      fibroblast growth factor-2 (FGF-2). Additionally, we discuss the feasibility of
      mathematical models that predict hNSC growth and differentiation under these
      culture conditions by adopting a negative feedback regulatory term. Our results
      indicate that the synergistic effect of culture dimensionality and hypoxic oxygen
      concentration in the presence of growth factors enhances the proliferation of
      viable, undifferentiated hNSCs. Moreover, the same synergistic effect in the
      absence of growth factors promotes the differentiation of hNSCs. Biotechnol.
      Bioeng. 2017;114: 1096-1106. (c) 2016 Wiley Periodicals, Inc.

PMID- 27869297
TI  - Association Between Results of Quality Assessment of Long-Term Care Facilities
      and Hospital-Acquired Pneumonia in Individuals with Stroke or Neurodegenerative
      Disease in Korea.

PMID- 27869296
TI  - Segmented linear modeling of CHO fed-batch culture and its application to large
      scale production.
AB  - We describe a systematic approach to model CHO metabolism during
      biopharmaceutical production across a wide range of cell culture conditions. To
      this end, we applied the metabolic steady state concept. We analyzed and modeled
      the production rates of metabolites as a function of the specific growth rate.
      First, the total number of metabolic steady state phases and the location of the
      breakpoints were determined by recursive partitioning. For this, the smoothed
      derivative of the metabolic rates with respect to the growth rate were used
      followed by hierarchical clustering of the obtained partition. We then applied a
      piecewise regression to the metabolic rates with the previously determined number
      of phases. This allowed identifying the growth rates at which the cells underwent
      a metabolic shift. The resulting model with piecewise linear relationships
      between metabolic rates and the growth rate did well describe cellular metabolism
      in the fed-batch cultures. Using the model structure and parameter values from a
      small-scale cell culture (2 L) training dataset, it was possible to predict
      metabolic rates of new fed-batch cultures just using the experimental specific
      growth rates. Such prediction was successful both at the laboratory scale with 2
      L bioreactors but also at the production scale of 2000 L. This type of modeling
      provides a flexible framework to set a solid foundation for metabolic flux
      analysis and mechanistic type of modeling. Biotechnol. Bioeng. 2017;114: 785-797.
      (c) 2016 The Authors. Biotechnology and Bioengineering Published by Wiley
      Periodicals, Inc.

PMID- 27869298
TI  - Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) for the
      early diagnosis of dementia across a variety of healthcare settings.
AB  - BACKGROUND: The Informant Questionnaire for Cognitive Decline in the Elderly
      (IQCODE) is a structured interview based on informant responses that is used to
      assess for possible dementia. IQCODE has been used for retrospective or
      contemporaneous assessment of cognitive decline. There is considerable interest
      in tests that may identify those at future risk of developing dementia. Assessing
      a population free of dementia for the prospective development of dementia is an
      approach often used in studies of dementia biomarkers. In theory, questionnaire
      based assessments, such as IQCODE, could be used in a similar way, assessing for
      dementia that is diagnosed on a later (delayed) assessment. OBJECTIVES: To
      determine the diagnostic accuracy of IQCODE in a population free from dementia
      for the delayed diagnosis of dementia (test accuracy with delayed verification
      study design). SEARCH METHODS: We searched these sources on 16 January 2016:
      ALOIS (Cochrane Dementia and Cognitive Improvement Group), MEDLINE Ovid SP,
      Embase Ovid SP, PsycINFO Ovid SP, BIOSIS Previews on Thomson Reuters Web of
      Science, Web of Science Core Collection (includes Conference Proceedings Citation
      Index) on Thomson Reuters Web of Science, CINAHL EBSCOhost, and LILACS BIREME. We
      also searched sources specific to diagnostic test accuracy: MEDION (Universities
      of Maastricht and Leuven); DARE (Database of Abstracts of Reviews of Effects, in
      the Cochrane Library); HTA Database (Health Technology Assessment Database, in
      the Cochrane Library), and ARIF (Birmingham University). We checked reference
      lists of included studies and reviews, used searches of included studies in
      PubMed to track related articles, and contacted research groups conducting work
      on IQCODE for dementia diagnosis to try to find additional studies. We developed
      a sensitive search strategy; search terms were designed to cover key concepts
      using several different approaches run in parallel, and included terms relating
      to cognitive tests, cognitive screening, and dementia. We used standardised
      database subject headings, such as MeSH terms (in MEDLINE) and other standardised
      headings (controlled vocabulary) in other databases, as appropriate. SELECTION
      CRITERIA: We selected studies that included a population free from dementia at
      baseline, who were assessed with the IQCODE and subsequently assessed for the
      development of dementia over time. The implication was that at the time of
      testing, the individual had a cognitive problem sufficient to result in an
      abnormal IQCODE score (defined by the study authors), but not yet meeting
      dementia diagnostic criteria. DATA COLLECTION AND ANALYSIS: We screened all
      titles generated by the electronic database searches, and reviewed abstracts of
      all potentially relevant studies. Two assessors independently checked the full
      papers for eligibility and extracted data. We determined quality assessment (risk
      of bias and applicability) using the QUADAS-2 tool, and reported quality using
      the STARDdem tool. MAIN RESULTS: From 85 papers describing IQCODE, we included
      three papers, representing data from 626 individuals. Of this total, 22% (N =
      135/626) were excluded because of prevalent dementia. There was substantial
      attrition; 47% (N = 295) of the study population received reference standard
      assessment at first follow-up (three to six months) and 28% (N = 174) received
      reference standard assessment at final follow-up (one to three years). Prevalence
      of dementia ranged from 12% to 26% at first follow-up and 16% to 35% at final
      follow-up.The three studies were considered to be too heterogenous to combine, so
      we did not perform meta-analyses to describe summary estimates of interest.
      Included patients were poststroke (two papers) and hip fracture (one paper). The
      IQCODE was used at three thresholds of positivity (higher than 3.0, higher than
      3.12 and higher than 3.3) to predict those at risk of a future diagnosis of
      dementia. Using a cut-off of 3.0, IQCODE had a sensitivity of 0.75 (95%CI 0.51 to
      0.91) and a specificity of 0.46 (95%CI 0.34 to 0.59) at one year following
      stroke. Using a cut-off of 3.12, the IQCODE had a sensitivity of 0.80 (95%CI 0.44
      to 0.97) and specificity of 0.53 (95C%CI 0.41 to 0.65) for the clinical diagnosis
      of dementia at six months after hip fracture. Using a cut-off of 3.3, the IQCODE
      had a sensitivity of 0.84 (95%CI 0.68 to 0.94) and a specificity of 0.87 (95%CI
      0.76 to 0.94) for the clinical diagnosis of dementia at one year after stroke.In
      generaI, the IQCODE was sensitive for identification of those who would develop
      dementia, but lacked specificity. Methods for both excluding prevalent dementia
      at baseline and assessing for the development of dementia were varied, and had
      the potential to introduce bias. AUTHORS' CONCLUSIONS: Included studies were
      heterogenous, recruited from specialist settings, and had potential biases. The
      studies identified did not allow us to make specific recommendations on the use
      of the IQCODE for the future diagnosis of dementia in clinical practice. The
      included studies highlighted the challenges of delayed verification dementia
      research, with issues around prevalent dementia assessment, loss to follow-up
      over time, and test non-completion potentially limiting the studies. Future
      research should recognise these issues and have explicit protocols for dealing
      with them.

PMID- 27869295
TI  - Noninvasive assessment of tissue-engineered graft viability by oxygen-17 magnetic
      resonance spectroscopy.
AB  - Transplantation of macroencapsulated tissue-engineered grafts (TEGs) is being
      investigated as a treatment for type 1 diabetes, but there is a critical need to
      measure TEG viability both in vitro and in vivo. Oxygen deficiency is the most
      critical issue preventing widespread implementation of TEG transplantation and
      delivery of supplemental oxygen (DSO) has been shown to enhance TEG survival and
      function in vivo. In this study, we demonstrate the first use of oxygen-17
      magnetic resonance spectroscopy (17 O-MRS) to measure the oxygen consumption rate
      (OCR) of TEGs and show that in addition to providing therapeutic benefits to
      TEGs, DSO with 17 O2 can also enable measurements of TEG viability.
      Macroencapsulated TEGs containing betaTC3 murine insulinoma cells were prepared
      with three fractional viabilities and provided with 17 O2 . Cellular metabolism
      of 17 O2 into nascent mitochondrial water (H217 O) was monitored by 17 O-MRS and,
      from the measured data, OCR was calculated. For comparison, OCR was
      simultaneously measured on a separate, but equivalent sample of cells with a well
      established stirred microchamber technique. OCR measured by 17 O-MRS agreed well
      with measurements made in the stirred microchamber device. These studies confirm
      that 17 O-MRS can quantify TEG viability noninvasively. Biotechnol. Bioeng.
      2017;114: 1118-1121. (c) 2016 Wiley Periodicals, Inc.

PMID- 27869299
TI  - Anaerobic reduction of 2,6-dinitrotoluene by Shewanella oneidensis MR-1: Roles of
      Mtr respiratory pathway and NfnB.
AB  - Dinitrotoluene (DNT) is a widely present pollutant in aquatic environments, and
      its biodegradation is an economically attractive way to effectively removal. In
      aquatic environments, the presence of electrochemically active bacteria (EAB)
      could contribute to the anaerobic bioreduction of DNT. However, the mechanism
      behind such a biodegradation process at gene level remains to be further
      elucidated. In this work, the anaerobic reduction of 2,6-dinitrotoluene (2,6-DNT)
      by Shewanella oneidensis MR-1, a typical EAB in aquatic environments, was
      investigated. S. oneidensis MR-1 was found to be able to obtain energy for growth
      through the anaerobic respiration on 2,6-DNT. Experimental results show that the
      Mtr respiratory pathway, a transmembrane electron transport chain, was involved
      in the 2,6-DNT bioreduction. Knockout of cymA or nfnB resulted in a substantial
      loss of its 2,6-DNT-reducing ability, indicating that both CymA and NfnB were the
      key proteins in the microbial electron transfer chain. The genetic analysis
      further confirms that the Mtr respiratory pathway and NfnB are mainly responsible
      for the anaerobic reduction of 2,6-DNT by S. oneidensis MR-1. This work is useful
      to better understand the anaerobic bioreduction of nitroaromatic compounds in
      aquatic environments and remediate the environments contaminated by nitroaromatic
      compounds. Biotechnol. Bioeng. 2017;114: 761-768. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27869300
TI  - Changes in Care Goals and Treatment Orders Around the Occurrence of Health
      Problems and Hospital Transfers in Dementia: A Prospective Study.
AB  - OBJECTIVES: To explore changes in care goals and treatment orders around the
      occurrence of pneumonia and intake problems, and whether hospitalization is in
      line with earlier agreed-upon do-not-hospitalize orders. DESIGN: Data were
      collected as part of the Dutch End of Life in Dementia study (2007-2011), a
      longitudinal observational study with up to 3.5 years of follow-up. SETTING: Long
      term care facilities (N = 28) in the Netherlands. PARTICIPANTS: Newly admitted
      nursing home patients (N = 372) in various stages of dementia. MEASUREMENTS:
      Semiannually, physicians completed questionnaires about care goals and treatment
      orders, and they continuously registered episodes of pneumonia, intake problems
      and hospitalization. We report on changes in care goals and treatment orders
      during follow-up in relation to the developing of pneumonia and intake problems
      and on hospitalization and reasons for hospitalization. RESULTS: The proportion
      of patients with palliative care goals and do-not-treat orders rose during follow
      up, especially before death. Treatment orders most frequently referred to
      resuscitation and hospitalization (do-not order increased from 73% to 92%, and
      from 28% to 76%, respectively). The proportions of patients with a palliative
      care goal and do-not-treat orders were similar after developing pneumonia, but
      increased after intake problems. During follow-up, 46 patients were hospitalized
      one or more times. Hospitalization occurred despite a do-not-hospitalize order in
      21% of decisions. The most frequently reported reason for hospitalization was a
      fracture, especially in patients with a do-not-hospitalize order. CONCLUSION:
      Care plans, including global care goals (predominantly palliative care goals),
      are made soon after admission, and specific treatment orders are agreed upon in
      more detail when the condition of the patient worsens. Establishing care plans
      shortly after nursing home admission may help to prevent burdensome treatment.

PMID- 27869303
TI  - Acute care - an important component of the continuum of care for HIV and
      tuberculosis in developing countries.

PMID- 27869301
TI  - Cerebral Amyloid Deposition Is Associated with Gait Parameters in the Mayo Clinic
      Study of Aging.
AB  - OBJECTIVES: To determine the cross-sectional association between cerebral amyloid
      beta (Abeta) deposition and gait. DESIGN: Cross-sectional. SETTING: Population
      based cohort study in Olmsted County, MN. PARTICIPANTS: Cognitively normal
      individuals (n = 611), aged 50 to 69 years, enrolled in the Mayo Clinic Study of
      Aging with concurrent PiB-PET imaging and gait assessment. Participants with a
      history of stroke, alcoholism, Parkinson's disease, subdural hematoma, traumatic
      brain injury, or normal pressure hydrocephalus were excluded. MEASUREMENTS: PiB
      PET SUVR was measured in prefrontal, orbitofrontal, parietal, temporal, anterior
      cingulate, posterior cingulate, and motor-specific regions of interest (ROIs).
      Gait parameters (speed, cadence, stride length, double support time, and intra
      individual stance time variability) were measured using GAITRite(r)
      instrumentation. Linear regression models were adjusted for age, sex, body mass
      index, education, APOE epsilon4 allele, Charlson comorbidity index, and
      depression. In secondary analyses, we additionally adjusted for neurodegeneration
      (hippocampal volume, FDG PET SUVR, and cortical thickness) in AD-associated
      regions. RESULTS: In fully adjusted models including neuroimaging measures of
      neurodegeneration, higher PiB-PET SUVR across all ROIs was associated with slower
      gait speed (P < .05 except for the parietal ROI), lower cadence and longer double
      support time (P <= .05 except for the motor ROI), and greater stance time
      variability (P < .05). In sex-stratified analyses, the association between higher
      PiB-PET SUVR across all ROIs and measures of gait was only present among women.
      CONCLUSION: PiB-PET SUVR across ROIs, independent of general measures of AD
      associated neurodegeneration, is associated with poorer performance on multiple
      gait parameters among cognitively normal women, aged 50 to 69 years. Longitudinal
      studies are needed to determine whether Abeta predicts gait decline in both women
      and men.

PMID- 27869304
TI  - Disclose or not? Effect of impression management tactics on hireability of
      persons with epilepsy.
AB  - OBJECTIVE: The purpose of this study is to determine the effect of assertive
      impression management (IM) tactics, such as personal storytelling and self
      promotion, on job interview outcomes of people with epilepsy. Specifically, the
      effect of IM on interviewers' subjective impressions and evaluation of
      hireability of job candidates with epilepsy were examined. METHODS: Ninety-nine
      master's level graduate students majoring in business or human resources were
      randomly assigned to three experimental conditions to view one of three 15-min
      video clips of a job applicant interviewing for a technical computer sales
      position. The three experimental conditions were (1) job applicant who did not
      disclose any disability, (2) job applicant with epilepsy who did not use IM
      tactics, and (3) job applicant with epilepsy who used IM tactics. After watching
      the job interview video portraying the experimental conditions, participants were
      asked to rate the job applicant in terms of general impression and hireability
      for the described position. RESULTS: The use of IM was found to have a
      significant effect on job interview outcomes (p < 0.01). Post hoc comparisons
      indicated that the average rating of business/human resources students on both
      general impression and hireability for the job applicant with epilepsy and IM
      condition were significantly higher than for the job applicant with epilepsy who
      did not use IM condition. Furthermore, mediation analysis revealed that general
      impression is a mediator for the relationship between IM and interview outcomes.
      SIGNIFICANCE: This study demonstrates that IM has a significant and positive
      effect on job interview outcomes for persons with epilepsy. IM can be used as a
      powerful strategy for empowering people with epilepsy to combat disability
      stigma, and offset negative perceptions of employers about the potential of this
      population to be productive workers.

PMID- 27869302
TI  - Brain Function Is Linked to LDL Cholesterol in Older Adults with Cardiovascular
      Risk.
AB  - OBJECTIVES: To determine how cardiovascular risk is associated with working
      memory task performance and task-related suppression of default-mode network
      (DMN) activity in cognitively intact older adults. DESIGN: A cross-sectional
      functional magnetic resonance imaging study of older adults with cardiovascular
      risk factors. SETTING: Rotman Research Institute, Baycrest Health Sciences.
      PARTICIPANTS: Thirty older adults with cardiovascular risk factors. MEASUREMENTS:
      Participants provided health information and a blood sample, and underwent
      functional magnetic resonance imaging during a working memory task and during a
      breath-hold task to assess cerebrovascular reactivity. RESULTS: Higher plasma low
      density lipoprotein cholesterol (LDL-C) was associated with poorer working memory
      task performance (P = 0.008) and reduced task-related DMN suppression (P =
      0.005). A composite index of cardiovascular risk, the Framingham General
      Cardiovascular Risk Profile, showed no associations with task performance or task
      related DMN suppression. These findings were independent of white matter burden
      and cerebrovascular reactivity and thus cannot be accounted for by individual
      differences in neurovascular health. CONCLUSION: These findings suggest a
      deleterious effect of elevated LDL-C on working memory task performance and task
      related DMN suppression in older adults with cardiovascular risk. The relations
      between the Framingham General Cardiovascular Risk Profile, cognitive task
      performance, and DMN function require further study.

PMID- 27869305
TI  - Analysis of falls in patients with epilepsy enrolled in the perampanel phase III
      randomized double-blind studies.
AB  - OBJECTIVE: To analyze occurrence of falls among patients with partial seizures,
      with/without secondarily generalized seizures (SGS), and primary generalized
      tonic-clonic seizures (PGTCS) in the perampanel phase III clinical studies.
      METHODS: Studies 304, 305, and 306 randomized subjects (>=12 years) with drug
      resistant partial seizures (with/without SGS) to perampanel 2, 4, 8, or 12 mg or
      placebo for double-blind treatment. The adverse event (AE) of falls was analyzed
      in the Safety Analysis Set (N = 1480). Study 332 randomized subjects aged >=12
      years with a diagnosis of PGTCS into perampanel 8 mg or placebo groups for double
      blind treatment. In a systematic review of reported falls in the study 332 Safety
      Analysis Set (N = 163), falls were queried to establish whether each was seizure
      related; subjects with falls resulting from a seizure were not included in this
      analysis. RESULTS: For studies 304/305/306, treatment-emergent falls occurred in
      5.1% perampanel-treated versus 3.4% placebo-treated subjects with partial
      seizures. Exposure-adjusted rate for falls (falls/subject-month of exposure) was
      greater for total perampanel than for placebo (0.0175 vs. 0.0093) and was dose
      related for those receiving perampanel. In subjects with SGS, incidence of
      treatment-emergent falls was 4.3% in perampanel and 4.0% in placebo groups.
      Exposure-adjusted rates were 0.0169 and 0.0097 falls per subject-month of
      exposure in perampanel and placebo, respectively. For study 332, 2.5% perampanel
      treated and 1.2% placebo-treated subjects with PGTCS had treatment-emergent falls
      that were not part of a seizure. Exposure-adjusted rates were 0.0169 and 0.0032
      falls per subject-month of exposure in perampanel and placebo, respectively.
      SIGNIFICANCE: Results of the perampanel studies suggest that patients with
      epilepsy should be monitored due to the common risk of falls.

PMID- 27869306
TI  - Roles of Multifunctional COP9 Signalosome Complex in Cell Fate and Implications
      for Drug Discovery.
AB  - The eight subunits containing COP9 signalosome (CSN) complex, is highly conserved
      among eukaryotes. CSN, identified as a negative regulator of photomorphogenesis,
      has also been demonstrated to be important in proteolysis, cellular signal
      transduction and cell cycle regulation in various eukaryotic organisms. This
      review mainly summarizes the roles of CSN in cell cycle regulation, signal
      transduction and apoptosis, and its potential as diagnostic biomarkers, drug
      targets for cancer and infectious diseases. J. Cell. Physiol. 232: 1246-1253,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27869307
TI  - Stupidity in the analytic field: Vicissitudes of the detachment process in
      adolescence.
AB  - This paper has the objective of broadening the understanding of technical aspects
      in working with adolescents who defend themselves against detachment from
      infantile aspects through defensive organizations. These organizations numb the
      adolescent toward both triangular reality and narcissistic defenses. The families
      of such young people may be part of the organization and the analyst can also be
      recruited to participate in it. But the analyst's perception can become blurry
      and this fact makes him appear stupid. Aspects of the myths of Narcissus and
      Oedipus are used here as models for studying stupidity. The analysis of a
      psychotic teenage girl who is symbiotic in relation to her family shows how the
      analytical field can be invaded by defensive configurations. Collusions of
      idealization and domination/submission involve the young person, her family and
      the analyst but the defensive organizations are only identified after their
      traumatic breakdown. The expansion of the symbolic network allows symbiotic
      transgenerational organizations to be identified, while models related to
      enactments prove helpful for understanding technical ups and downs. The paper
      ends with imaginative conjectures where Oedipus, as 'patient', is compared to the
      patient discussed here. These conjectures lead to reinterpretations of aspects of
      the Oedipus myth. The reinterpretations, together with the theoretical and
      clinical study, may serve as models for understanding the technical ups and downs
      in working with troubled teens.

PMID- 27869308
TI  - Signaling in the Auditory System: Implications in Hair Cell Regeneration and
      Hearing Function.
AB  - Ear is a sensitive organ involved in hearing and balance function. The complex
      signaling network in the auditory system plays a crucial role in maintaining
      normal physiological function of the ear. The inner ear comprises a variety of
      host signaling pathways working in synergy to deliver clear sensory messages. Any
      disruption, as minor as it can be, has the potential to affect this finely tuned
      system with temporary or permanent sequelae including vestibular deficits and
      hearing loss. Mutations linked to auditory symptoms, whether inherited or
      acquired, are being actively researched for ways to reverse, silence, or suppress
      them. In this article, we discuss recent advancements in understanding the
      pathways involved in auditory system signaling, from hair cell development
      through transmission to cortical centers. Our review discusses Notch and Wnt
      signaling, cell to cell communication through connexin and pannexin channels, and
      the detrimental effects of reactive oxygen species on the auditory system. There
      has been an increased interest in the auditory community to explore the signaling
      system in the ear for hair cell regeneration. Understanding signaling pathways in
      the auditory system will pave the way for the novel avenues to regenerate sensory
      hair cells and restore hearing function. J. Cell. Physiol. 232: 2710-2721, 2017.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27869309
TI  - Roles of Notch Signaling in Adipocyte Progenitor Cells and Mature Adipocytes.
AB  - Adipose tissues, composed with mature adipocytes and preadipocytic stromal/stem
      cells, play crucial roles in whole body energy metabolism and regenerative
      medicine. Mature adipocytes are derived and differentiated from mesenchymal stem
      cells (MSCs) or preadipocytes. This differentiation process, also called
      adipogenesis, is regulated by several signaling pathways and transcription
      factors. Notch1 signaling is a highly conserved pathway that is indispensable for
      stem cell hemostasis and tissue development. In adipocyte progenitor cells,
      Notch1 signaling regulates the adipogenesis process including proliferation and
      differentiation of the adipocyte progenitor cells in vitro. Notably, the roles of
      Notch1 signaling in beige adipocytes formation, adipose development, and
      function, and the whole body energy metabolism have been recently reported. Here,
      we mainly review and discuss the roles of Notch1 signaling in adipogenesis in
      vitro as well as in beige adipocytes formation, adipocytes dedifferentiation, and
      function in vivo. J. Cell. Physiol. 232: 1258-1261, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27869310
TI  - TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture
      Model of the Corneal Epithelium.
AB  - TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by
      hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4
      during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells.
      TRPV4 is a late differentiation feature that is concentrated in the apical
      membrane of the outmost cell layer of the stratified epithelia. Ca2+ imaging
      experiments showed that TRPV4 activation with GSK1016790A produced an influx of
      calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the
      involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the
      development of transepithelial electrical resistance (TER) as an indicator of the
      tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to
      establish the TJ. In differentiated epithelia, activation of TRPV4 increases the
      TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth
      Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show
      here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition
      or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2,
      an EGF-activated channel that forms heteromeric complexes with TRPV4, is also
      concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This
      suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4
      TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the
      correct establishment of TJ in corneal epithelia and as well as the regulation of
      both the barrier function of TJ and its ability to respond to EGF. J. Cell.
      Physiol. 232: 1794-1807, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27869311
TI  - Hypoxia suppresses serum deprivation-induced degradation of the nucleus pulposus
      cell extracellular matrix through the JNK and NF-kappaB pathways.
AB  - Intervertebral disc (IVD) degeneration is associated with the imbalance between
      anabolism and catabolism of the nucleus pulposus (NP) extracellular matrix (ECM).
      Serum deprivation (SD) has been reported to exacerbate IVD degeneration; however,
      the effect of SD on ECM metabolism is not fully understood. Hypoxia plays
      important roles in maintaining the physiological functions of IVD cells; however,
      whether hypoxia has any effect on NP ECM production under conditions of SD is
      still unclear. In the current study, we established an in vitro SD model by
      exposing NP cells to serum-free medium. SD decreased the expression of aggrecan
      and collagen II, as well as the production of sulfated glycosaminoglycan (sGAG)
      in a time-dependent manner. However, hypoxia abolished SD-mediated down
      regulation of aggrecan and collagen II expression via JNK1/2 activation.
      Moreover, hypoxia abolished SD-induced MMP-3 and MMP-13 expression by inhibiting
      NF-kappaB activation, p65 translocation, and MMP-3 and MMP-13 promoter activity.
      These results indicated that, hypoxia maintained ECM production under conditions
      of SD. This effect was elicited in part through JNK1/2-mediated up-regulation of
      matrix gene expression and down-regulation of MMP expression, through the
      inhibition of NF-kappaB. (c) 2017 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res 35:2059-2066, 2017.

PMID- 27869313
TI  - The role of the miR-17-92 cluster in neurogenesis and angiogenesis in the central
      nervous system of adults.
AB  - It is well known that neurogenesis is not the only concern for the fully
      functional recovery after brain or spinal cord injury, as it has been shed light
      on the critical role of angiogenesis in improving neurological functional
      recovery. Angiogenesis and neurogenesis coordinately interact with each other in
      the developing and adult brain, during which they may respond to similar
      mediators and receptors, in which they share a common posttranscriptional
      regulator: the miR-17-92 cluster. The miR-17-92 cluster was initially described
      as an oncogene and was later demonstrated to drive key physiological and
      pathological responses during development and diseases respectively. It has been
      reported that the miR-17-92 cluster regulates both neurogenesis and angiogenesis.
      The miR-17-92 cluster modulates neural progenitor cells proliferation not only
      during development but also during neurological disorders such as stroke. It has
      also been shown that the endothelial miR-17-92 cluster regulates angiogenesis
      during embryonic stage and adulthood. In this review, we have discussed the
      actions of the miR-17-92 cluster in neuronal and vascular plasticity, and its
      potential as a novel therapeutic strategy for CNS injury. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27869312
TI  - The effect of EMG biofeedback assisted pelvic floor muscle therapy on symptoms of
      the overactive bladder syndrome in women: A randomized controlled trial.
AB  - AIMS: The overactive bladder syndrome (OAB) is defined as urinary urgency,
      usually accompanied by frequency and nocturia, with or without urgency urinary
      incontinence. Biofeedback-assisted pelvic muscle therapy (BAPFMT) is a first-line
      treatment option for OAB. The aims of this study were to determine the efficacy
      and effectiveness of BAPFMT on symptoms of OAB after 9 weeks of treatment and to
      detect changes EMG activity of individual pelvic floor muscles (PFM) with the
      MAPLe. METHODS: Patients were randomly divided into an intervention group that
      received BAPFMT with the MAPLe or into a control group which received only toilet
      behavior and lifestyle instructions. The Pelvic Floor Inventories (PeLFIs), the
      King's Health Questionnaire (KHQ), a voiding dairy, a 24 h pad-test, and vaginal
      EMG registration of the pelvic floor with the MAPLe were used at inclusion and
      after 9 weeks follow-up to determine the effect of BAPFMT on complaints of OAB
      and Quality of Life (QoL). RESULTS: Fifty-eight patients were included. The
      PeLFIs, KHQ, voiding dairy, and 24 h pad-test showed significant improvements in
      the intervention group compared to the control group in complaints of OAB and
      QoL. EMG activity showed significant improvements for specific individual muscles
      at the different sides and depths for rest, maximal voluntary contraction, and
      endurance. CONCLUSIONS: EMG BAPFMT is effective in the OAB syndrome in women. It
      significantly reduces symptoms and complaints of OAB and increases QoL for
      patients. It shows that EMG changes in individual PFM, measured with the MAPLe,
      are relevant and related to symptom reduction.

PMID- 27869316
TI  - Phylogeny, phylogenetic inference, and cranial evolution in pitheciids and Aotus.
AB  - Pitheciids, one of the major radiations of New World monkeys endemic to South and
      Central America, are distributed in the Amazon and Orinoco basins, and include
      Callicebus, Cacajao, Chiropotes, and Pithecia. Molecular phylogenetics strongly
      support pitheciid monophyly, whereas morphological analyses infer a range of
      phylogenies including a sister relationship between Aotus and Callicebus. We
      collected geometric morphometric cranial data from pitheciids and Aotus, and used
      cranial data for distance-based phylogenetic analysis and tests of phylogenetic
      signal. Phylogenetic analyses of pitheciids were repeated with Lagothrix,
      Callimico, and Saimiri outgroups for Procrustes shape with and without Aotus
      based on the whole cranium and six anatomical regions. All phylogenetic signal
      tests were significant, and tree lengths were shortest and had the least
      morphological change over the phylogeny for Procrustes residuals from the cranial
      base and palate. The majority of phylogenetic analyses of Procrustes shape for
      pitheciids without Aotus supported the molecular phylogeny, and with Aotus
      included the majority inferred an Aotus-Callicebus clade, although three analyses
      with Callimico as outgroup supported the molecular phylogeny. The morphological
      similarity of Aotus and Callicebus is likely a mix of plesiomorphy, allometry,
      and homoplasy, and future phylogenetic inference of living and extinct
      platyrrhine taxa should consider the impact of these factors alongside outgroup
      selection and cranial region.

PMID- 27869315
TI  - Aminoalkyl Derivatives of 8-Alkoxypurine-2,6-diones: Multifunctional 5-HT1A /5
      HT7 Receptor Ligands and PDE Inhibitors with Antidepressant Activity.
AB  - In the search for potential psychotropic agents, a new series of 3,7-dimethyl-
      and 1,3-dimethyl-8-alkoxypurine-2,6-dione derivatives of arylpiperazines,
      perhydroisoquinolines, or tetrahydroisoquinolines with flexible alkylene spacers
      (5-16 and 21-32) were synthesized and evaluated for 5-HT1A /5-HT7 receptor
      affinities as well as PDE4B1 and PDE10A inhibitory properties. The 1-(4-(4-(2
      hydroxyphenyl)piperazin-1-yl)butyl)-3,7-dimethyl-8-propoxypurine-2,6-dione (16)
      and 7-(2-hydroxyphenyl)piperazinylalkyl-1,3-dimethyl-8-ethoxypurine-2,6-diones
      (31 and 32) as potent dual 5-HT1A /5-HT7 receptor ligands with antagonistic
      activity produced an antidepressant-like effect in the forced swim test in mice.
      This effect was similar to that produced by citalopram. All the tested compounds
      were stronger phosphodiesterase isoenzyme inhibitors than theophylline and
      theobromine. The most potent compounds, 15 and 16, were characterized by 51 and
      52% inhibition, respectively, of PDE4B1 activity at a concentration of 10-5  M.
      Concerning the above findings, it may be assumed that the inhibition of PDE4B1
      may impact on the signal strength and specificity resulting from antagonism
      toward the 5-HT1 and 5-HT7 receptors, especially in the case of compounds 15 and
      16. This dual receptor and enzyme binding mode was analyzed and explained via
      molecular modeling studies.

PMID- 27869314
TI  - Runx1 Orchestrates Sphingolipid Metabolism and Glucocorticoid Resistance in
      Lymphomagenesis.
AB  - The three-membered RUNX gene family includes RUNX1, a major mutational target in
      human leukemias, and displays hallmarks of both tumor suppressors and oncogenes.
      In mouse models, the Runx genes appear to act as conditional oncogenes, as
      ectopic expression is growth suppressive in normal cells but drives lymphoma
      development potently when combined with over-expressed Myc or loss of p53. Clues
      to underlying mechanisms emerged previously from murine fibroblasts where ectopic
      expression of any of the Runx genes promotes survival through direct and indirect
      regulation of key enzymes in sphingolipid metabolism associated with a shift in
      the "sphingolipid rheostat" from ceramide to sphingosine-1-phosphate (S1P).
      Testing of this relationship in lymphoma cells was therefore a high priority. We
      find that ectopic expression of Runx1 in lymphoma cells consistently perturbs the
      sphingolipid rheostat, whereas an essential physiological role for Runx1 is
      revealed by reduced S1P levels in normal spleen after partial Cre-mediated
      excision. Furthermore, we show that ectopic Runx1 expression confers increased
      resistance of lymphoma cells to glucocorticoid-mediated apoptosis, and elucidate
      the mechanism of cross-talk between glucocorticoid and sphingolipid metabolism
      through Sgpp1. Dexamethasone potently induces expression of Sgpp1 in T-lymphoma
      cells and drives cell death which is reduced by partial knockdown of Sgpp1 with
      shRNA or direct transcriptional repression of Sgpp1 by ectopic Runx1. Together
      these data show that Runx1 plays a role in regulating the sphingolipid rheostat
      in normal development and that perturbation of this cell fate regulator
      contributes to Runx-driven lymphomagenesis. J. Cell. Biochem. 118: 1432-1441,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27869317
TI  - How to make a sterile helper.
AB  - The sterile worker castes found in the colonies of social insects are often cited
      as archetypal examples of altruism in nature. The challenge is to explain why
      losing the ability to mate has evolved as a superior strategy for transmitting
      genes into future generations. We propose that two conditions are necessary for
      the evolution of sterility: completely overlapping generations and monogamy. A
      review of the literature indicates that when these two conditions are met we
      consistently observe the evolution of sterile helpers. We explain the theory and
      evidence behind these ideas, and discuss the importance of ecology in predicting
      whether sterility will evolve using examples from social birds, mammals, and
      insects. In doing so, we offer an explanation for the extraordinary lifespans of
      some cooperative species which hint at ways in which we can unlock the secrets of
      long life.

PMID- 27869319
TI  - The Ca2+ sensitizer CK-2066260 increases myofibrillar Ca2+ sensitivity and
      submaximal force selectively in fast skeletal muscle.
AB  - KEY POINTS: We report that the small molecule CK-2066260 selectively slows the
      off-rate of Ca2+ from fast skeletal muscle troponin, leading to increased
      myofibrillar Ca2+ sensitivity in fast skeletal muscle. Rodents dosed with CK
      2066260 show increased hindlimb muscle force and power in response to submaximal
      rates of nerve stimulation in situ. CK-2066260 has no effect on free cytosolic
      [Ca2+ ] during contractions of isolated muscle fibres. We conclude that fast
      skeletal muscle troponin sensitizers constitute a potential therapy to address an
      unmet need of improving muscle function in conditions of weakness and premature
      muscle fatigue. ABSTRACT: Skeletal muscle dysfunction occurs in many diseases and
      can lead to muscle weakness and premature muscle fatigue. Here we show that the
      fast skeletal troponin activator, CK-2066260, counteracts muscle weakness by
      increasing troponin Ca2+ affinity, thereby increasing myofibrillar Ca2+
      sensitivity. Exposure to CK-2066260 resulted in a concentration-dependent
      increase in the Ca2+ sensitivity of ATPase activity in isolated myofibrils and
      reconstituted hybrid sarcomeres containing fast skeletal muscle troponin C.
      Stopped-flow experiments revealed a ~2.7-fold decrease in the Ca2+ off-rate of
      isolated troponin complexes in the presence of CK-2066260 (6 vs. 17 s-1 under
      control conditions). Isolated mouse flexor digitorum brevis fibres showed a
      rapidly developing, reversible and concentration-dependent force increase at
      submaximal stimulation frequencies. This force increase was not accompanied by
      any changes in the free cytosolic [Ca2+ ] or its kinetics. CK-2066260 induced a
      slowing of relaxation, which was markedly larger at 26 degrees C than at 31
      degrees C and could be linked to the decreased Ca2+ off-rate of troponin C. Rats
      dosed with CK-2066260 showed increased hindlimb isometric and isokinetic force in
      response to submaximal rates of nerve stimulation in situ producing significantly
      higher absolute forces at low isokinetic velocities, whereas there was no
      difference in force at the highest velocities. Overall muscle power was increased
      and the findings are consistent with a lack of effect on crossbridge kinetics. In
      conclusion, CK-2066260 acts as a fast skeletal troponin activator that may be
      used to increase muscle force and power in conditions of muscle weakness.

PMID- 27869321
TI  - Performance and selectivity of cationic nanoparticle pseudo-stationary phases in
      electrokinetic chromatography.
AB  - Electrokinetic chromatography (EKC) is a powerful analytical technique that uses
      an ionic pseudo-stationary phase (PSP) to separate neutral compounds. Although
      anionic surfactants are the most common choice for PSP, cationic latex
      nanoparticles are an attractive alternative. Reversible addition-fragmentation
      chain transfer (RAFT) polymerization was used to synthesize several types of
      diblock copolymers that self-assemble into latex nanoparticles, which were
      characterized by a variety of techniques including diffusion NMR. The performance
      of each nanoparticle as a PSP was studied by using a homologous series of ketones
      and linear solvation energy relationships (LSER) analysis. A cationic homopolymer
      coating was found to be necessary to prevent band broadening caused by analyte
      interactions with nanoparticles adsorbed to the capillary surface. No significant
      difference in methylene selectivity or LSER parameters was observed between
      nanoparticles with different cationic shells, but differences were observed
      between nanoparticles with different hydrophobic cores. Cationic latex
      nanoparticles behaved more like anionic latex nanoparticles than like cationic
      surfactants, suggesting that selectivity is primarily driven by the hydrophobic
      portion of a PSP. Cationic latex nanoparticles in combination with a homopolymer
      cationic capillary coating are an excellent choice for EKC analyses where an
      anodic electroosmotic flow is required.

PMID- 27869320
TI  - Molecular epidemiology of HIV-1 among the HIV infected people of Manipur,
      Northeastern India: Emergence of unique recombinant forms.
AB  - According to the Joint National Programme on HIV/AIDS (UNAIDS), the northeastern
      region of India has the highest HIV prevalence in the country. This study was
      conducted to determine the current HIV-1 molecular epidemiology of Manipur, a
      state in northeast India. Blood samples from HIV-1 seropositive subjects were
      collected between June 2011 and February 2014. The partial regions of HIV-1
      genes; pol and tat-vpu-env were independently amplified, sequenced, analyzed, and
      genotyped. Based on all sequences generated from 110 samples using pol and/or tat
      vpu-env gene, the overall HIV-1 genotypes distribution of Manipur was as follows:
      65.45% (72/110) subtype C, 32.73% (36/110) unique recombinant forms (URFs), and
      1.82% (2/110) subtype B. The distribution of HIV-1 genotypes among the risk
      groups was: heterosexual: 58.33% (35/60) subtype C, 38.33% (23/60) URFs, and
      3.34% (2/60) subtype B; intravenous drug users (IDUs): 85.36% (35/41) subtype C,
      9.76% (4/41) URFs, and 4.88% (2/41) subtype B; mother to child (MTC): 50% (3/6)
      URFs and 50% (3/6) subtype C and blood transfusion: 100% (3/3) subtype C. The
      findings for the first time revealed the emergence of URFs of HIV-1 in Manipur
      which is predominant among the sexual and MTC risk groups as compared to IDUs.
      Taking together, this study illustrated that Manipur is the "recombinant hotspot
      of HIV" of India. The results will provide the clinical importance for continuous
      monitoring of HIV-infections in order to design appropriate prevention measures
      to limit the spread of new HIV infections.

PMID- 27869322
TI  - TMEM230 stop codon mutation is rare in parkinson's disease and essential tremor
      in eastern China.

PMID- 27869323
TI  - Comparative treatment effectiveness of direct acting antiviral regimens for
      hepatitis C: Data from the Veterans administration.
AB  - BACKGROUND AND AIMS: Data addressing real world effectiveness of direct acting
      antiviral agents in hepatitis C infected patients are now emerging. This study
      compared the sustained virologic response rates achieved 12 weeks post-treatment
      in patients treated with three such agents by the Veterans Health Administration.
      METHODS: A retrospective cohort study was conducted using patients who terminated
      treatment by July 1, 2015. Data were retrieved from the Veterans Health
      Administration electronic medical records system. Patients were included if
      sufficient viral load laboratory data were available to determine sustained
      virologic response. Applying an intention to treat approach and logistic
      regression analysis, the sustained virologic response rates achieved were
      compared across drug regimens. RESULTS: A total of 11 464 patients met study
      selection criteria. Without controlling for other risk factors, sustained
      virologic response at least 12 weeks post treatment was achieved in 92% of
      ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and
      83% of simeprevir/sofosbuvir patients. After adjusting for patient
      characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%)
      patients were statistically more likely than
      ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate
      sustained virologic response. Human immunodeficiency virus, hepatitis B
      infection, diabetes, obesity, previous treatment history and augmentation therapy
      using ribavirin did not impact sustained virologic response rates. Sustained
      virologic response rates were lower for patients under age 65, with cirrhosis,
      decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a
      non-genotype 1 infection. Women and Caucasian patients were more likely to
      achieve a sustained virologic response. CONCLUSIONS: All three direct acting
      antiviral regimens appear highly effective in achieving sustained virologic
      response.

PMID- 27869324
TI  - Overlaps between multiple system atrophy and multiple sclerosis: A novel
      perspective.

PMID- 27869325
TI  - A novel therapeutic approach for synucleinopathies.

PMID- 27869326
TI  - Peroxiredoxin-2 up-regulation in inflammatory bowel disease: Friend or foe?
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are chronic multi-factorial
      inflammatory disorders. Accumulating investigations have provided compelling
      evidence that describe the interplay of a complex genetic landscape and
      inappropriate inflammatory response to intestinal microbes in disease
      etiopathogenesis but still pose challenges in diagnostic practices. METHOD: In
      this study, comparative proteomic analysis was conducted to identify disease
      specific proteins underlying IBD pathogenetic mechanisms. Total blood proteins of
      the IBD patients and healthy subjects were analyzed with one-dimensional
      electrophoresis; differentially expressed bands were excised and subjected to
      matrix-assisted laser desorption ionization-time of flight mass spectrometry
      along with nanoflow liquid chromatography electrospray ionization-tandem mass
      spectrometry analysis. Presence of glycosylation, hydroxylation, and
      phosphorylation post-translational modifications was further investigated by
      immunoprecipitation. RESULTS: Peroxiredoxin-2 (PRDX2) and hemoglobin-subunits
      proteins, which are closely involved in the response to oxidative stress, were
      identified. PRDX2 was selected for further validation using western blot and
      reverse transcription-polymerase chain reaction. PRDX2 overexpression was
      restricted to the protein level within the membrane fraction. Immunoprecipitation
      identified PRDX2 to be post-translationally glycosylated and phosphorylated.
      CONCLUSION: Our findings demonstrate the implication of PRDX2 in IBD. Future
      studies are required to establish its functional role and to determine the
      clinical utility.

PMID- 27869327
TI  - The Selective Serotonin Reuptake Inhibitor Fluoxetine Directly Inhibits
      Osteoblast Differentiation and Mineralization During Fracture Healing in Mice.
AB  - Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment
      of depression has been linked to osteoporosis. In this study, we investigated the
      effect of chronic SSRI use on fracture healing in two murine models of bone
      regeneration. First, we performed a comprehensive analysis of endochondral bone
      healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most
      commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days
      after fracture and demonstrated a significantly smaller and biomechanically
      weaker bony hard-callus at 28 days. In order to further dissect the mechanism
      that resulted in a smaller bony regenerate, we used an intramembranous model of
      bone healing and revealed that fluoxetine treatment resulted in a significantly
      smaller bony callus at 7 and 14 days postinjury. In order to test whether the
      smaller bony regenerate following fluoxetine treatment was caused by an
      inhibition of osteogenic differentiation and/or mineralization, we employed in
      vitro experiments, which established that fluoxetine treatment decreases
      osteogenic differentiation and mineralization and that this effect is serotonin
      independent. Finally, in a translational approach, we tested whether cessation of
      the medication would result in restoration of the regenerative potential.
      However, histologic and MUCT analysis revealed non-union formation in these
      animals with fibrous tissue interposition within the callus. In conclusion,
      fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and
      mineralization, shown in two disparate murine models of bone repair.
      Discontinuation of the drug did not result in restoration of the healing
      potential, but rather led to complete arrest of the repair process. Besides the
      well-established effect of SSRIs on bone homeostasis, our study provides strong
      evidence that fluoxetine use negatively impacts fracture healing. (c) 2017
      American Society for Bone and Mineral Research.

PMID- 27869328
TI  - Real-life efficacy and safety of paritaprevir/ritonavir, ombitasvir, and
      dasabuvir in chronic hepatitis C patients in Hong Kong.
AB  - BACKGROUND AND AIM: In registration studies, combination therapy of
      paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with and without
      ribavirin for 12-24 weeks can achieve > 90% sustained virological response (SVR)
      for genotype 1 hepatitis C virus (HCV) infection. However, data in Asia is
      scanty. We aimed to study the efficacy and safety of this combination therapy in
      chronic hepatitis C patients in Hong Kong. METHODS: We retrospectively analyzed
      data from six local hospitals that have prescribed PrOD with and without
      ribavirin to patients with genotype 1 chronic HCV infection as part of a global
      compassionate program. RESULTS: Among 41 patients treated, 35 (85%) patients had
      genotype 1b HCV infection, 6 (15%) had co-infection with human immunodeficiency
      virus, 35 (85%) failed previous peginterferon and ribavirin therapy, 25 (61%) had
      compensated liver cirrhosis, and 3 (7%) had liver transplantation. Thirty-five
      (85%) patients received 12-week treatment and six patients received 24-week
      treatment; 26 (63%) patients received ribavirin combination. Thirty-nine (95%;
      95% confidence interval 88.5-100%) patients had undetectable HCV RNA at 12-week
      post-treatment, that is, SVR. The two patients who did not develop SVR
      discontinued treatment prematurely; both of them were treatment experienced with
      liver cirrhosis complicated by acute renal failure unrelated to the treatment of
      PrOD and ribavirin. No patient had hepatic decompensation. CONCLUSIONS:
      Paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin is
      effective and safe in patients with genotype 1 HCV infection in real-life
      clinical setting in Hong Kong.

PMID- 27869329
TI  - Novel compound heterozygous synaptojanin-1 mutation causes l-dopa-responsive
      dystonia-parkinsonism syndrome.

PMID- 27869330
TI  - Stretchable Porous Carbon Nanotube-Elastomer Hybrid Nanocomposite for Harvesting
      Mechanical Energy.
AB  - A stretchable porous nanocomposite (PNC) is reported based on a hybrid of a
      multiwalled carbon nanotubes network and a poly(dimethylsiloxane) matrix for
      harvesting energy from mechanical interactions. The deformation-enabled energy
      generating process makes the PNC applicable to various mechanical interactions,
      including pressing, stretching, bending, and twisting. It can be potentially used
      as an energy solution for wearable electronics.

PMID- 27869331
TI  - Morbidity and mortality following poliomyelitis - a lifelong follow-up.
AB  - BACKGROUND AND PURPOSE: In the world today 10-20 million people are still living
      with late effects of poliomyelitis (PM), but the long-term consequences of the
      disease are not well known. The aim of this study was to describe lifelong
      morbidity and mortality among Danes who survived PM. METHODS: Data from official
      registers for a cohort of 3606 Danes hospitalized for PM in the period 1940-1954
      were compared with 13 762 age- and gender-matched controls. RESULTS: Compared
      with controls, mortality was moderately increased for both paralytic as well as
      non-paralytic PM cases; Hazard Ratio, 1.31 (95% confidence interval, 1.18-1.44)
      and 1.09 (95% confidence interval, 1.00-1.19), respectively. Hospitalization
      rates were approximately 1.5 times higher among both paralytic and non-paralytic
      PM cases as compared with controls. Discharge diagnoses showed a broad spectrum
      of diseases. There were no major differences in morbidities between paralytic and
      non-paralytic PM cases. CONCLUSIONS: Poliomyelitis has significant long-term
      consequences on morbidity and mortality of both paralytic and non-paralytic
      cases.

PMID- 27869334
TI  - Prediction of long-term prognosis by heteroplasmy levels of the m.3243A>G
      mutation in patients with the mitochondrial encephalomyopathy, lactic acidosis
      and stroke-like episodes syndrome.
AB  - BACKGROUND AND PURPOSE: Our aim was to determine the prognostic value of urine
      and blood heteroplasmy in patients with the m.3243A>G mutation. METHODS: Adults
      with the m.3243A>G mutation referred to our institution between January 2000 and
      May 2014 were retrospectively included. The relationship between their baseline
      clinical characteristics, their mutation load in urine and blood, and major
      adverse events (MAEs) during follow-up, defined as medical complications
      requiring a hospitalization or complicated by death, was studied. RESULTS: Of the
      43 patients (age 45.6 +/- 13.3 years) included in the study, 36 patients were
      symptomatic, including nine with evidence of focal brain involvement, and seven
      were asymptomatic. Over a 5.5 +/- 4.0 year mean follow-up duration, 14 patients
      (33%) developed MAEs. Patients with MAEs had a higher mutation load than others
      in urine (60.1% +/- 13.8% vs. 40.6% +/- 26.2%, P = 0.01) and in blood (26.9% +/-
      18.4% vs. 16.0% +/- 12.1%, P = 0.03). Optimal cutoff values for the prediction of
      MAEs were 45% for urine and 35% for blood. In multivariate analysis, mutation
      load in urine >=45% [odds ratio 25.3; 95% confidence interval (CI) 1.1-567.8; P =
      0.04], left ventricular hypertrophy (odds ratio 16.7; 95% CI 1.3- 222.5; P =
      0.03) and seizures (odds ratio 48.3; 95% CI 2.5-933; P = 0.01) were associated
      with MAEs. CONCLUSIONS: Patients with the m.3243A>G mutation are at high risk of
      MAEs, which can be independently predicted by mutation load in urine >=45%, a
      personal history of seizures, and left ventricular hypertrophy.

PMID- 27869333
TI  - Patient-specific 3D FLAIR for enhanced visualization of brain white matter
      lesions in multiple sclerosis.
AB  - PURPOSE: To improve the conspicuity of white matter lesions (WMLs) in multiple
      sclerosis (MS) using patient-specific optimization of single-slab 3D fluid
      attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). MATERIALS
      AND METHODS: Sixteen MS patients were enrolled in a prospective 3.0T MRI study.
      FLAIR inversion time and echo time were automatically optimized for each patient
      during the same scan session based on measurements of the relative proton density
      and relaxation times of the brain tissues. The optimization criterion was to
      maximize the contrast between gray matter (GM) and white matter (WM), while
      suppressing cerebrospinal fluid. This criterion also helps increase the contrast
      between WMLs and WM. The performance of the patient-specific 3D FLAIR protocol
      relative to the fixed-parameter protocol was assessed both qualitatively and
      quantitatively. RESULTS: Patient-specific optimization achieved a statistically
      significant 41% increase in the GM-WM contrast ratio (P < 0.05) and 32% increase
      in the WML-WM contrast ratio (P < 0.01) compared with fixed-parameter FLAIR. The
      increase in WML-WM contrast ratio correlated strongly with echo time (P < 10-11
      ). Two experienced neuroradiologists indicated substantially higher lesion
      conspicuity on the patient-specific FLAIR images over conventional FLAIR in 3-4
      cases (intrarater correlation coefficient ICC = 0.72). In no case was the image
      quality of patient-specific FLAIR considered inferior to conventional FLAIR by
      any of the raters (ICC = 0.32). CONCLUSION: Changes in proton density and
      relaxation times render fixed-parameter FLAIR suboptimal in terms of lesion
      contrast. Patient-specific optimization of 3D FLAIR increases lesion conspicuity
      without scan time penalty, and has potential to enhance the detection of subtle
      and small lesions in MS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J.
      MAGN. RESON. IMAGING 2017;46:557-564.

PMID- 27869335
TI  - Australia's rural medical workforce: Supply from its medical schools against
      career stage, gender and rural-origin.
AB  - OBJECTIVE: The aim of this study was to explore the association between career
      stage and rural medical workforce supply among Australian-trained medical
      graduates. DESIGN AND SETTING: Descriptive analysis using the national Medicine
      in Australia: Balancing Employment and Life (MABEL) longitudinal study.
      PARTICIPANTS: Australian-trained GPs and other specialists who participated in
      the MABEL study, 2008-2013. MAIN OUTCOME MEASURE(S): Proportions of GPs and
      specialists working in rural locations, according to career stage (establishing,
      early, mid and late), gender and childhood-origin type (rural versus
      metropolitan). RESULTS: Logistic regression models revealed that establishing-
      and early-career GPs had significantly higher likelihood (OR 1.67 and 1.38,
      respectively) of working rurally, but establishing and early-career doctors were
      significantly less likely (OR 0.34 and 0.43, respectively) to choose general
      practice, contributing proportionally fewer rural GPs overall (OR 0.77 and 0.75,
      respectively) compared to late-career doctors. For specialists, there were no
      significant associations between career cohorts and rural practice. Overall,
      there was a significantly lower likelihood (OR 0.83) of establishing-career
      doctors practising rurally. Women were similarly likely to be rural GPs but less
      likely to be rural specialists, while rural-origin was consistently associated
      with higher odds of rural practice. CONCLUSIONS: The supply of Australia's rural
      medical workforce from its medical schools continues to be challenging, with
      these data highlighting both their source and associations with doctors at
      different career stages. Despite large investments through rural medical training
      and rural workforce recruitment and retention policies, these data confirm
      continued reliance on internationally trained medical graduates for large
      proportions of rural supply is likely.

PMID- 27869336
TI  - Use of the synergist piperonyl butoxide can slow the development of alpha
      cypermethrin resistance in the whitefly Bemisia tabaci.
AB  - The development of insecticide resistance in insect pests of crops is a growing
      threat to sustainable food production, and strategies that slow the development
      of resistance are therefore urgently required. The insecticide synergist
      piperonyl butoxide (PBO) inhibits certain insect detoxification systems and so
      may delay the evolution of metabolic resistance. In the current study we
      characterized resistance development in the silverleaf whitefly, Bemisia tabaci,
      after selection with either a neonicotinoid (thiacloprid) or pyrethroid (alpha
      cypermethrin) insecticide alone or in combination with PBO. Resistance
      development was significantly suppressed (> 60%) in the line selected with alpha
      cypermethrin + PBO compared to the line selected with alpha-cypermethrin alone.
      RNA sequencing (RNAseq) analyses revealed an increase in frequency of a knock
      down resistance mutation but no differentially expressed genes were identified
      that could explain the sensitivity shift. No significant difference was observed
      in the level of resistance between the thiacloprid and thiacloprid + PBO selected
      lines, and RNA sequencing (RNAseq) analyses revealed that the cytochrome P450
      monooxygenase CYP6CM1, known to metabolize neonicotinoids, was significantly
      upregulated (>10-fold) in both lines. The findings of this study demonstrate that
      PBO used in combination with certain insecticides can suppress the development of
      resistance in a laboratory setting; however, the mechanism by which PBO supresses
      resistance development remains unclear.

PMID- 27869337
TI  - "Bis-Click" Ligation of DNA: Template-Controlled Assembly, Circularisation and
      Functionalisation with Bifunctional and Trifunctional Azides.
AB  - Ligation and circularisation of oligonucleotides containing terminal triple bonds
      was performed with bifunctional or trifunctional azides. Both reactions are high
      yielding. Template-assisted bis-click ligation of two individual non
      complementary oligonucleotide strands was accomplished to yield heterodimers
      exclusively. In this context, the template fulfils two functions: it accelerates
      the ligation reaction and controls product assembly (heterodimer vs. homodimer
      formation). Intermolecular bis-click circularisation of one oligonucleotide
      strand took place without template assistance. For construction of
      oligonucleotides with terminal triple bonds in the nucleobase side chain, 7- or 5
      functionalised 7-deaza-dA and dU residues were used. These oligonucleotides are
      directly accessible by solid-phase synthesis. When trifunctional azides were
      employed instead of bifunctional linkers, functionalisation of the remaining
      azido group was performed with small molecules such as 1-ethynyl pyrene, biotin
      propargyl amide or with ethynylated oligonucleotides. By this means, branched DNA
      was constructed.

PMID- 27869338
TI  - Conductance Oscillations in a Graphene/Nanocluster Hybrid Material: Toward Large
      Area Single-Electron Devices.
AB  - Large assemblies of self-organized aluminum nanoclusters embedded in an oxide
      layer are formed on graphene templates and used to build tunnel-junction devices.
      Unexpectedly, single-electron-transport behavior with well-defined Coulomb
      oscillations is observed for a record junction area of up to 100 um2 containing
      millions of metal islands. Such graphene-metal nanocluster hybrid materials offer
      new prospects for single-electron electronics.

PMID- 27869339
TI  - Multifunctional Benzoquinone Additive for Efficient and Stable Planar Perovskite
      Solar Cells.
AB  - Device stability of planar perovskite solar cells is improved by virtue of
      multifunctional BQ additive. The morphology and crystal quality of the perovskite
      films are improved because BQ slows the rate of perovskite crystal formation.
      Electron transfer from perovskite to BQ reduces charge-recombination losses, and
      the oxidizing ability of BQ effectively suppresses the formation of metallic lead
      and improves device lifetime.

PMID- 27869340
TI  - Dual 5' Cap Labeling Based on Regioselective RNA Methyltransferases and
      Bioorthogonal Reactions.
AB  - The ability to detect and localize defined RNA strands inside living cells
      requires probes with high specificity, sensitivity, and signal-to-background
      ratio. To track low-abundant biomolecules, such as strands of regular mRNA, and
      distinguish fluorescence signal from the background after bioorthogonal reactions
      in cells, it is imperative to employ turn-on concepts. Here, we have presented a
      straightforward enzymatic approach to allow site-specific modification of two
      different positions on the 5' cap of eukaryotic mRNA with either identical or
      different small functional groups. The approach relies on two methyltransferases
      and analogues of their natural co-substrate, and it can be extended to a three
      enzyme cascade reaction for their in situ production. Subsequent labeling by
      using bioorthogonal click reactions provided access to double labeling with
      identical fluorophores or dual labeling with two different reporter groups, as
      exemplified by a Cy5 dye, a FRET pair, and a fluorophore/biotin combination. Our
      dual-labeling strategy addresses the need for increased sensitivity and should
      improve the signal-to-background ratio after bioorthogonal reactions in cells.

PMID- 27869341
TI  - Pseudonotohymena antarctica n. g., n. sp. (Ciliophora, Hypotricha), a New Species
      from Antarctic Soil.
AB  - A new soil ciliate, Pseudonotohymena antarctica n. g., n. sp., from King George
      Island, Antarctica, is described based on live observation, protargol
      impregnation, and its 18S rRNA gene. The new genus Pseudonotohymena is
      morphologically similar to the genus Notohymena Blatterer and Foissner in the
      following characteristics: 18 fronto-ventral-transverse cirri, a flexible body,
      undulating membranes, dorsomarginal kineties, and the number of cirri in the
      marginal rows. However, Pseudonotohymena differs from Notohymena particularly in
      the dorsal ciliature, that is, in possessing a nonfragmented dorsal kinety (vs.
      fragmented). In addition, the molecular phylogenetic relationship of the new
      species differs from that of Notohymena species. On the basis of the
      morphological features, the genetic data, and morphogenesis, we establish P.
      antarctica n. g., n. sp. In addition, the cyst morphology of this species is
      described.

PMID- 27869342
TI  - Fluorogenic 2D Peptidosheet Unravels CD47 as a Potential Biomarker for Profiling
      Hepatocellular Carcinoma and Cholangiocarcinoma Tissues.
AB  - A 2D peptidosheet unravels CD47 as a potential biomarker to image hepatocarcinoma
      and cholangiocarcinoma cells and tissues. Supramolecular assembly between water
      soluble 2D MoS2 and a peptide probe produces the 2D peptidosheet suited for the
      profiling of hepatocarcinoma and cholangiocarcinoma tissues over healthy tissues
      on clinical specimens.

PMID- 27869344
TI  - The Importance of Materials Design to Make Ions Flow: Toward Novel Materials
      Platforms for Bioelectronics Applications.
AB  - Chemical design criteria for materials for bioelectronics applications using a
      series of copolymer derivatives based on poly(3-hexylthiophene) are established.
      Directed chemical design via side-chain functionalization with polar groups
      allows manipulation of ion transport and ion-to-electron transduction. Insights
      gained will permit increased use of the plethora of materials employed in the
      organic electronics area for application in the bioelectronics field.

PMID- 27869343
TI  - An Arbitrary Color Light Emitter.
AB  - The integration of a light-emitting transistor based on
      graphene/insulator/semiconductor with downconversion emitters enables the
      manipulation of emitted light covering the whole chromaticity space, including
      white-light emission. This novel arbitrary-color light emitter offers a promising
      approach for new applications in optoelectronic devices ranging from displays to
      solid-state lighting.

PMID- 27869345
TI  - Solution-Processed MoS2 /Organolead Trihalide Perovskite Photodetectors.
AB  - Integration of organic/inorganic hybrid perovskites with metallic or
      semiconducting phases of 2D MoS2 nanosheets via solution processing is
      demonstrated. The results show that the collection of charge carriers is strongly
      dependent on the electronic properties of the 2D MoS2 with metallic MoS2 showing
      high responsivity and the semiconducting phase exhibiting high on/off ratios.

PMID- 27869346
TI  - Association between dialysis treatment and cognitive decline: A study from the
      Project in Sado for Total Health (PROST), Japan.
AB  - AIM: Evidence for the association between dialysis treatment and cognitive
      decline is limited. The present study aimed to determine whether dialysis
      treatment is associated with cognitive decline in adult outpatients of a general
      hospital in Japan. METHODS: This was a cross-sectional substudy of the Project in
      Sado for Total Health (PROST). Total Health PROST targeted adult outpatients of a
      general hospital in Sado City, Niigata, Japan. Among 753 patients (mean age 68.1
      +/- 11.6 years) analyzed, 66 received dialysis. Cognitive state was evaluated
      using the Mini-Mental State Examination, and those with a Mini-Mental State
      Examination score <24 were considered "cognitively declined." The prevalence of
      cognitive decline was compared by odds ratios calculated with multiple logistic
      regression analysis. Variables included in the analyses were dialysis, age, sex
      and self-reported histories of hypertension, diabetes, stroke and ischemic heart
      disease. RESULTS: Of the 66 dialysis patients, 24 (36.4%) showed cognitive
      decline, whereas 172 (25.0%) of 687 non-dialysis patients showed cognitive
      decline. The age and sex-adjusted odds ratio for cognitive decline in dialysis
      patients was 2.57 (95% confidence interval 1.43-4.61), relative to non-dialysis
      patients. The odds ratio remained significant (odds ratio 2.69, 95% confidence
      interval 1.49-4.88) even after adjusting for all covariates. CONCLUSION: The
      prevalence of cognitive decline was high in dialysis patients relative to non
      dialysis patients among outpatients of a general hospital in Japan. Geriatr
      Gerontol Int 2017; 17: 1584-1587.

PMID- 27869347
TI  - MYB transcription factor gene involved in sex determination in Asparagus
      officinalis.
AB  - Dioecy is a plant mating system in which individuals of a species are either male
      or female. Although many flowering plants evolved independently from
      hermaphroditism to dioecy, the molecular mechanism underlying this transition
      remains largely unknown. Sex determination in the dioecious plant Asparagus
      officinalis is controlled by X and Y chromosomes; the male and female karyotypes
      are XY and XX, respectively. Transcriptome analysis of A. officinalis buds showed
      that a MYB-like gene, Male Specific Expression 1 (MSE1), is specifically
      expressed in males. MSE1 exhibits tight linkage with the Y chromosome, specific
      expression in early anther development and loss of function on the X chromosome.
      Knockout of the MSE1 orthologue in Arabidopsis induces male sterility. Thus, MSE1
      acts in sex determination in A. officinalis.

PMID- 27869348
TI  - Agricultural intensification and drought frequency increases may have landscape
      level consequences for ephemeral ecosystems.
AB  - Ephemeral wetlands in arid regions are often degraded or destroyed through poor
      land-use practice long before they are ever studied or prioritized for
      conservation. Climate change will likely also have implications for these
      ecosystems given forecast changes in rainfall patterns in many arid environments.
      Here, we present a conceptual diagram showing typical and modified ephemeral
      wetlands in agricultural landscapes and how modification impacts on species
      diversity and composition.

PMID- 27869349
TI  - High-resolution Raman Spectroscopy for the Nanostructural Characterization of
      Explosive Nanodiamond Precursors.
AB  - The specific attributes of nanodiamonds have attracted increasing interest for
      electronics or biomedical applications. An efficient synthetic route towards
      nanodiamonds is via detonation of hexolite (i.e. a mixture of TNT [2,4,6
      trinitrotoluene] and RDX [1,3,5-trinitro-1,3,5-triazine]). In particular,
      detonation of hexolite crystallized by spray flash evaporation (SFE) yields
      extremely small diamonds (<4 nm). To unravel the detonation mechanism, a
      structural characterization of the explosives is required but is challenging due
      to their thermal instability. We demonstrate a combination of conventional Raman
      spectroscopy and tip-enhanced Raman spectroscopy (TERS) for resolving
      morphological and structural differences of differently prepared hexolite
      nanocomposites. The experiments allow for the first time a structural
      differentiation of individual TNT and RDX crystals and 15-20 nm sized core-shell
      structures, consequently providing a general approach to investigate the actual
      composition of mixtures on the nanometer scale.

PMID- 27869350
TI  - Skeletogenesis of Myiopsitta monachus (Psittaciformes) and sequence
      heterochronies in Aves.
AB  - The ossification sequence of Myiopsitta monachus was determined. Myiopsitta has a
      similar sequence to other altricial birds, with delayed skeletons compared to
      precocial species. The hindlimbs ossify before the forelimbs, a condition that
      could be linked to altriciality. To determine the stability of the sequences of
      ossification across birds, we selected species of different groups of Aves and
      used event-pairing method and character mapping on a phylogeny. Our results show
      that the homogeneity in the development of birds was supported by 56.77% of the
      character states. Event-pair cracking phylogenetic method was applied to identify
      sequence heterochronies. Results reveal a high number of heterochronies and show
      that the long bones in limbs may behave as modules. In Myiopsitta, the ossa
      ectethmoidale and mesethmoidale ossify early. These bones provide the origin site
      of the Psittaciformes' novel adductor m. ethmomandibularis, associated with
      strong bite forces, and its acceleration in the sequence may correspond to the
      functional hypothesis. Also, the early appearance of some hyoid apparatus
      elements occurs, and could be related to the development of tongue in
      Psittaciformes and its role in handling food, and is in concordance with the
      functional and size hypothesis.

PMID- 27869352
TI  - Configurationally Stable Chiral Dithia-Bridged Hetero[4]helicene Radical Cation:
      Electronic Structure and Absolute Configuration.
AB  - A stable chiral hetero[4]helicene radical cation was synthesized and
      characterized by UV/Vis absorption and EPR spectroscopy, as well as X-ray
      crystallography. For the first time, a combination of chiroptical methods
      involving ECD, ORD, and VCD, supported by quantum mechanical predictions, enabled
      the elucidation of the absolute configuration of such open-shell helical species.

PMID- 27869351
TI  - Social participation, willingness and quality of life: A population-based study
      among older adults in rural areas of China.
AB  - AIM: The present study aimed to reflect the current situation of social
      participation in rural areas of China, willingness to participate in social
      activities, association between health-related quality of life and social
      participation, and factors related to social participation. METHODS: A total of
      2644 rural adults aged 60 years and older were randomly selected and surveyed
      with a self-rating questionnaire. We used the unified definition of social
      participation in our study. The Medical Outcomes Study Short-Form Health Survey
      was used to measure health-related quality of life. RESULTS: The overall
      engagement of social activities was 26%. Those who participated in social
      activities were more likely to have high scores of health-related quality of
      life. Older men with a high educational level (OR 1.59, 95% CI 1.01-2.29) living
      alone or with a spouse (OR 1.51, 95% CI 1.08-2.12), high objective social support
      (OR 1.08, 95% CI 1.00-1.17) and high support utilization (OR 1.13, 95% CI 1.07
      1.21) were inclined to engage in social participation. Older women with high
      individual income (OR 1.74, 95% CI 1.25-2.43), single marital status (OR 1.53,
      95% CI 1.11-2.10), normal weight (OR 1.92, 95% CI 1.10-3.34), overweight (OR
      2.28, 95% CI 1.24-4.19), living alone or with a spouse (OR 1.55, 95% CI 1.20
      2.00), objective social support (OR 1.11, 95% CI 1.04-1.18) and subjective social
      support (OR 1.15, 95% CI 1.10-1.20) were more willing to engage in social
      participation. CONCLUSIONS: Engagement in social activities is relatively low in
      rural areas, and associations of willingness and health-related quality of life
      with social participation were found. Policy-makers and government workers should
      make appropriate types of encouragement policies around social participation for
      older adults in rural areas. Geriatr Gerontol Int 2017; 17: 1593-1602.

PMID- 27869353
TI  - Recent Progress in Ionic Iridium(III) Complexes for Organic Electronic Devices.
AB  - Ionic iridium(III) complexes are emerging with great promise for organic
      electronic devices, owing to their unique features such as ease of molecular
      design and synthesis, excellent photophysical properties, superior redox
      stability, and highly efficient emissions of virtually all colors. Here, recent
      progress on new material design, regarding photo- and electroluminescence is
      highlighted, including several interesting topics such as: i) color-tuning
      strategies of cationic iridium(III) complexes, ii) widespread utilization in
      phosphorescent light-emitting devices fabricated by not only solution processes
      but also vacuum evaporation deposition, and iii) potential applications in data
      record, storage, and sercurity. Results on anionic iridium(III) complexes and
      "soft salts" are also discussed, indicating a new related subject. Finally, a
      brief outlook is suggested, pointing out that ionic iridium(III) complexes should
      play a more significant role in future organic electronic materials technology.

PMID- 27869355
TI  - Delivery of Flightless I Neutralizing Antibody from Porous Silicon Nanoparticles
      Improves Wound Healing in Diabetic Mice.
AB  - Flightless I (Flii) is elevated in human chronic wounds and is a negative
      regulator of wound repair. Decreasing its activity improves healing responses.
      Flii neutralizing antibodies (FnAbs) decrease Flii activity in vivo and hold
      significant promise as healing agents. However, to avoid the need for repeated
      application in a clinical setting and to protect the therapeutic antibody from
      the hostile environment of the wound, suitable delivery vehicles are required. In
      this study, the use of porous silicon nanoparticles (pSi NPs) is demonstrated for
      the controlled release of FnAb to diabetic wounds. We achieve FnAb loading
      regimens exceeding 250 ug antibody per mg of vehicle. FnAb-loaded pSi NPs
      increase keratinocyte proliferation and enhance migration in scratch wound
      assays. Release studies confirm the functionality of the FnAb in terms of Flii
      binding. Using a streptozotocin-induced model of diabetic wound healing, a
      significant improvement in healing is observed for mice treated with FnAb-loaded
      pSi NPs compared to controls, including FnAb alone. FnAb-loaded pSi NPs treated
      with proteases show intact and functional antibody for up to 7 d post-treatment,
      suggesting protection of the antibodies from proteolytic degradation in wound
      fluid. pSi NPs may therefore enable new therapeutic approaches for the treatment
      of diabetic ulcers.

PMID- 27869354
TI  - Efficacy of olopatadine hydrochloride 0.1%, emedastine difumarate 0.05%, and
      loteprednol etabonate 0.5% for Chinese children with seasonal allergic
      conjunctivitis: a randomized vehicle-controlled study.
AB  - BACKGROUND: Allergic conjunctivitis (AC) is a disease of various agents that
      affects the physical and mental health of children. Although the most effective
      therapy has not been found so far, it is essential to explore the considerable
      therapeutic method. We compared the clinical efficacy of olopatadine, emedastine,
      loteprednol etabonate (LE), and vehicle for treating seasonal allergic
      conjunctivitis (SAC) in Chinese children. METHODS: Eighty cases of 160 eyes aged
      from 5 to 10 years with SAC were available and those subjects were randomly
      distributed into 4 groups. Both their eyes received olopatadine hydrochloride
      0.1% twice a day, emedastine difumarate 0.05% twice a day, or LE 0.5% 4 times a
      day, respectively, whereas those of the control group received artificial tears
      (AT) 0.5% 3 times a day. This study was conducted successfully and the
      observations were collected before treatment and on day 8 (+/-1 day) and day 15
      (+/-2 days) afterward. The principal measurement of efficacy was focused on the
      signs and symptoms of the subjects, evaluated before and after treatment, in
      addition to visual acuity (VA) and fundus oculi. RESULTS: On day 8 (+/-1 day) and
      day 15 (+/-2 days), all the antiallergic agents were found to be more effective
      than vehicle (p < 0.05) in terms of all the symptoms and signs. However, there
      was no statistical significance (p >= 0.05) shown among the treatment groups.
      There were no evident changes in VA and no clinically significant changes were
      observed in fundus oculi. CONCLUSION: After the treatment, the efficacy presented
      a similar distribution among the trial groups.

PMID- 27869356
TI  - Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor: A novel treatment
      option for nurse practitioners treating patients with psoriatic disease.
AB  - BACKGROUND AND PURPOSE: Apremilast is an oral nonbiologic medication approved for
      the treatment of adult patients with active psoriatic arthritis and for patients
      with moderate to severe plaque psoriasis. This article summarizes the efficacy
      and safety of apremilast and provides characterization of the novel medication
      with clinical perspectives to successfully incorporate this therapy into practice
      for appropriate patients. DATA SOURCES: A review and synthesis of the results
      from the ESTEEM (Efficacy and Safety Trial Evaluating the Effects of Apremilast
      in Psoriasis) phase 3 clinical studies evaluating the efficacy, safety, and
      tolerability of apremilast for the treatment of moderate to severe plaque
      psoriasis was conducted. CONCLUSIONS: Results from the ESTEEM clinical trial
      program demonstrate that apremilast significantly reduces the severity of
      moderate to severe plaque psoriasis, has an acceptable safety profile, and is
      generally well tolerated. IMPLICATIONS FOR PRACTICE: The novel mechanism of
      action, convenience of oral administration, and acceptable side effect profile
      make this medication an attractive choice for clinicians treating patients with
      plaque psoriasis.

PMID- 27869357
TI  - The impact of endoscopic sinus surgery on paranasal physiology in simulated sinus
      cavities.
AB  - BACKGROUND: Surgery improves symptoms for the majority of chronic rhinosinusitis
      (CRS) patients; however, physiological changes in the sinus cavities remain
      poorly characterized. Direct measurement of changes in airflow, pressure,
      temperature, humidity, and intranasal spray distribution following surgery is
      technically challenging. Accordingly, we have used computational fluid dynamic
      modeling to quantify how these parameters change postoperatively. METHODS:
      Computed tomography images from a normal control, a patient with CRS
      preoperatively and postoperatively, and a patient following an endoscopic Lothrop
      procedure (ELP) were used to create 4 three-dimensional models of the sinus
      cavities. Changes in physiologic parameters and topical drug distribution were
      modeled (inhaled air at 16 degrees C and 10% humidity) at the maxillary ostium,
      frontal recess, and sphenoid ostium. RESULTS: Large differences were seen between
      models. Following surgery, the maxillary ostia were found on average to be cooler
      (by 2.4 degrees C), with an increased airflow (0.26 m/second; from 0 m/second),
      and a 9% reduction in absolute humidity. Sphenoid ostial parameters followed a
      similar trend. Significant changes in frontal recess physiology were seen
      following ELP in which the recess was 4.2 degrees C cooler, had increased airflow
      (0.76 m/second) and a 17% reduction in absolute humidity. Topical drug
      distribution increased with surgery, particularly after ELP. CONCLUSION: Surgery
      changes the geometry and physiology of the paranasal sinuses. These changes are
      likely to have an impact on wound healing, mucociliary function, and microbial
      ecology in postoperative cavities. Application of this model to further
      understand the effects of surgery may help to optimize surgical techniques and
      improve topical drug delivery.

PMID- 27869358
TI  - Disease Systems Analysis of Bone Mineral Density and Bone Turnover Markers in
      Response to Alendronate, Placebo, and Washout in Postmenopausal Women.
AB  - A previously established mechanism-based disease systems model for osteoporosis
      that is based on a mathematically reduced version of a model describing the
      interactions between osteoclast (bone removing) and osteoblast (bone forming)
      cells in bone remodeling has been applied to clinical data from women (n = 1,379)
      receiving different doses and treatment regimens of alendronate, placebo, and
      washout. The changes in the biomarkers, plasma bone-specific alkaline phosphatase
      activity (BSAP), urinary N-telopeptide (NTX), lumbar spine bone mineral density
      (BMD), and total hip BMD, were linked to the underlying mechanistic core of the
      model. The final model gave an accurate description of all four biomarkers for
      the different treatments. Simulations were used to visualize the dynamics of the
      underlying network and the natural disease progression upon alendronate treatment
      and discontinuation. These results complement the previous applications of this
      mechanism-based disease systems model to data from various treatments for
      osteoporosis.

PMID- 27869359
TI  - Pitfalls in the use of epinephrine for anaphylaxis: patient and provider
      opportunities for improvement.
AB  - BACKGROUND: Epinephrine remains the mainstay of treatment for life-threatening
      allergic reactions. A number of challenges are encountered with epinephrine,
      resulting in underutilization and misutilization of epinephrine. The purpose of
      this study was to identify the scope of epinephrine pitfalls and opportunities
      for improvement in the management of allergy emergencies. METHODS: A PubMed
      search from 1990 to 2015 was performed to identify all cases and reports
      pertaining to the use and misuse of epinephrine for anaphylaxis. Studies were
      assessed for obstacles or complications related to proper administration of
      epinephrine for treatment of allergic reactions, and were divided into problems
      originating with patients compared to healthcare providers. RESULTS: There were
      1840 publications related to epinephrine use, of which 61 reports met inclusion
      criteria for pitfalls in the use of epinephrine. The most common problems
      reported related to lack of autoinjector availability (22), inadequate education
      of patients or providers (9), uncertainty about when or how to administer
      epinephrine (9), concern for systemic effects (13), failure to administer (8),
      and accidental administration (2). Responsibility for errors was divided among
      patients (18), providers (39), or both (4). CONCLUSION: Epinephrine is a potent
      medication with lifesaving indications and is the standard of care for treatment
      of anaphylaxis. The delivery of epinephrine in both trained and untrained
      populations carries certain pitfalls and complications that can have serious
      consequences. Identification of the scope of the problem is an important step in
      improving education for both providers and patients who are tasked with use of
      epinephrine for allergy emergencies.

PMID- 27869361
TI  - Clinical outcomes according to molecular subtypes in stage II-III breast cancer
      patients treated with neoadjuvant chemotherapy followed by surgery and
      radiotherapy.
AB  - AIM: We evaluated the tumor response and clinical outcomes according to molecular
      subtypes in stage II-III breast cancer patients who received neo-adjuvant
      chemotherapy (NAC) followed by surgery and radiotherapy. METHODS: We
      retrospectively analyzed 329 patients with clinical stage II-III breast cancer
      who received NAC followed by surgery and radiotherapy. Luminal A and B, HER2
      enriched and triple-negative subgroups were identified. RESULTS: The overall
      pathologic complete response (pCR) rate after NAC was 20.1% and the HER2-enriched
      subgroup had the highest pCR rate (43.6%), whereas luminal A showed the lowest
      rate of pCR (4.6%). The median follow-up duration was 55 months (range, 5-98
      months). The 5-year overall survival (OS) and disease-free survival (DFS) rates
      were 88.9% and 72.9%, respectively. In subgroup analysis, according to the
      pathologic response (pCR vs non-pCR), the triple-negative subtype exhibited a
      significant difference in 5-year OS rate (100.0% vs 71.6%, P = 0.005) and 5-year
      DFS rate (93.1% vs 55.1%, P < 0.001). A distinct survival difference according to
      molecular subtype was found, particularly in the non-pCR group (5-year OS and
      DFS, P < 0.001, respectively). CONCLUSIONS: The non-pCR group showed
      significantly decreased 5-year OS and DFS rates compared to the pCR group,
      especially in triple negative and HER2-enriched breast cancer patients. A
      significant difference in survival rates and molecular subtypes was found in
      patients who failed to attain pCR.

PMID- 27869360
TI  - Association between ratio indexes of body composition phenotypes and metabolic
      risk in Italian adults.
AB  - The ratio between fat mass (FM) and fat-free mass (FFM) has been used to
      discriminate individual differences in body composition and improve prediction of
      metabolic risk. Here, we evaluated whether the use of a visceral adipose tissue
      to-fat-free mass index (VAT:FFMI) ratio was a better predictor of metabolic risk
      than a fat mass index to fat-free mass index (FMI:FFMI) ratio. This is a cross
      sectional study including 3441 adult participants (age range 18-81; men/women:
      977/2464). FM and FFM were measured by bioelectrical impedance analysis and VAT
      by ultrasonography. A continuous metabolic risk Z score and harmonised
      international criteria were used to define cumulative metabolic risk and
      metabolic syndrome (MetS), respectively. Multivariate logistic and linear
      regression models were used to test associations between body composition indexes
      and metabolic risk. In unadjusted models, VAT:FFMI was a better predictor of MetS
      (OR 8.03, 95%CI 6.69-9.65) compared to FMI:FFMI (OR 2.91, 95%CI 2.45-3.46).
      However, the strength of association of VAT:FFMI and FMI:FFMI became comparable
      when models were adjusted for age, gender, clinical and sociodemographic factors
      (OR 4.06, 95%CI 3.31-4.97; OR 4.25, 95%CI 3.42-5.27, respectively). A similar
      pattern was observed for the association of the two indexes with the metabolic
      risk Z score (VAT:FFMI: unadjusted b = 0.69 +/- 0.03, adjusted b = 0.36 +/- 0.03;
      FMI:FFMI: unadjusted b = 0.28 +/- 0.028, adjusted b = 0.38 +/- 0.02). Our results
      suggest that there is no real advantage in using either VAT:FFMI or FMI:FFMI
      ratios as a predictor of metabolic risk in adults. However, these results warrant
      confirmation in longitudinal studies.

PMID- 27869363
TI  - Is the Memorial Sloan Kettering Cancer Centre (MSKCC) sarcoma nomogram useful in
      an Asian population?
AB  - AIM: A nomogram for prediction of 12-year sarcoma-specific survival has been
      developed based on patients with soft tissue sarcomas treated in Memorial Sloan
      Kettering Cancer Centre (MSKCC). We aim to evaluate the predictive accuracy of
      the MSKCC sarcoma nomogram in a cohort of patients treated at an Asian
      institution. This has not been validated in an Asian population and thus its
      universal applicability remains unproven. MATERIALS AND METHODS: Between 1990 and
      2013, 840 adult patients underwent treatment for primary soft tissue sarcoma
      (STS) at the National Cancer Centre Singapore. Patients who presented with
      locally recurrent or metastatic disease were excluded from the analysis. The
      variables included in the MSKCC nomogram included age at diagnosis, tumor size,
      histologic grade, histologic subtype, depth and site. A total of 399 patients
      were left for analysis. The nomogram was validated by assessing its extent of
      discrimination and level of calibration. RESULTS: All patients had deep tumors.
      Disease occurred most commonly in the lower extremity (n = 149 [37.3%]), the most
      common histologic subtype was "Others" (angiosarcoma, ewing's sarcoma,
      endometrial stromal sarcoma, sarcoma NOS [not otherwise specified] and
      rhabdomyosarcoma). Sixty-four percent of all patients had high-grade tumors while
      36% had low-grade tumors. The median patient age at diagnosis was 54 years
      (range: 17-88 years). The median follow up time for all patients and surviving
      patients were 29 (range: 1-174) and 33 (range: 1-157) months, respectively. The
      observed 5- and 10-year sarcoma-specific survival were 55% and 33%, respectively.
      The concordance index was 0.71. For level of calibration, the observed
      correspondence between predicted and actual outcomes suggest that the MSKCC
      nomogram generally predicts well for patients with higher survival probability,
      but consistently overpredicts survival for the other groups, in our cohort of
      patients. CONCLUSION: The MSKCC sarcoma nomogram was found to be accurate in
      terms of extent of discrimination. In terms of level of calibration, it generally
      predicts well for patients with higher survival probability, but consistently
      overpredicts survival for the other groups in our population.

PMID- 27869362
TI  - Fractal Geometry-Based Decrease in Trimethoprim-Sulfamethoxazole Concentrations
      in Overweight and Obese People.
AB  - Trimethoprim-sulfamethoxazole (TMP-SMX) is one of the most widely drugs on earth.
      The World Health Organization recommends it as an essential basic drug for all
      healthcare systems. Dosing is inconsistently based on weight, assuming linear
      relationships. Given that obesity is now a global "pandemic" it is vital that we
      evaluate the effect of obesity on trimethoprim-sulfamethoxazole concentrations.
      We conducted a prospective clinical experiment based on optimized design
      strategies and artificial intelligence algorithms and found that weight and body
      mass index (BMI) had a profound effect on drug clearance and volume of
      distribution, and followed nonlinear fractal geometry-based relationships. The
      findings were confirmed by demonstrating decreased TMP-SMX peak and area under
      the concentration-time curves in overweight patients based on standard regression
      statistics. The nonlinear relationships can now be used to identify new TMP-SMX
      doses in overweight and obese patients for each of the infections caused by the
      >60 pathogens for which the drug is indicated.

PMID- 27869364
TI  - Assessing the reliability of ecotoxicological studies: An overview of current
      needs and approaches.
AB  - In general, reliable studies are well designed and well performed, and enough
      details on study design and performance are reported to assess the study. For
      hazard and risk assessment in various legal frameworks, many different types of
      ecotoxicity studies need to be evaluated for reliability. These studies vary in
      study design, methodology, quality, and level of detail reported (e.g., reviews,
      peer-reviewed research papers, or industry-sponsored studies documented under
      Good Laboratory Practice [GLP] guidelines). Regulators have the responsibility to
      make sound and verifiable decisions and should evaluate each study for
      reliability in accordance with scientific principles regardless of whether they
      were conducted in accordance with GLP and/or standardized methods. Thus, a
      systematic and transparent approach is needed to evaluate studies for
      reliability. In this paper, 8 different methods for reliability assessment were
      compared using a number of attributes: categorical versus numerical scoring
      methods, use of exclusion and critical criteria, weighting of criteria, whether
      methods are tested with case studies, domain of applicability, bias toward GLP
      studies, incorporation of standard guidelines in the evaluation method, number of
      criteria used, type of criteria considered, and availability of guidance
      material. Finally, some considerations are given on how to choose a suitable
      method for assessing reliability of ecotoxicity studies. Integr Environ Assess
      Manag 2017;13:640-651. (c) 2016 The Authors. Integrated Environmental Assessment
      and Management published by Wiley Periodicals, Inc. on behalf of Society of
      Environmental Toxicology & Chemistry (SETAC).

PMID- 27869365
TI  - Editorial: Asian Congress of Biotechnology 2015.

PMID- 27869367
TI  - Errata.

PMID- 27869366
TI  - Evolution of female-specific wingless forms in bagworm moths.
AB  - The evolution of winglessness in insects has been typically interpreted as a
      consequence of developmental and other adaptations to various environments that
      are secondarily derived from a winged morph. Several species of bagworm moths
      (Insecta: Lepidoptera, Psychidae) exhibit a case-dwelling larval life style along
      with one of the most extreme cases of sexual dimorphism: wingless female adults.
      While the developmental process that led to these wingless females is well known,
      the origins and evolutionary transitions are not yet understood. To examine the
      evolutionary patterns of wing reduction in bagworm females, we reconstruct the
      molecular phylogeny of over 30 Asian species based on both mitochondrial
      (cytochrome c oxidase subunit I) and nuclear (28S rRNA) DNA sequences. Under a
      parsimonious assumption, the molecular phylogeny implies that: (i) the
      evolutionary wing reduction towards wingless females consisted of two steps:
      (Step I) from functional wings to vestigial wings (nonfunctional) and (Step II)
      from vestigial wings to the most specialized vermiform adults (lacking wings and
      legs); and (ii) vermiform morphs evolved independently at least twice. Based on
      the results of our study, we suggest that the evolutionary changes in the
      developmental system are essential for the establishment of different wingless
      forms in insects.

PMID- 27869368
TI  - Acta 3.0 - The state of your journal.

PMID- 27869370
TI  - Conjunctival malignant melanoma in Denmark. Epidemiology, treatment and prognosis
      with special emphasis on tumorigenesis and genetic profile.

PMID- 27869371
TI  - VORWORT.

PMID- 27869372
TI  - Pathogenesis and clinical presentation of rosacea as a key for a symptom-oriented
      therapy.
AB  - Rosacea is a common chronic inflammatory skin disorder that typically occurs in
      adults and affects the face. Synonyms of rosacea include "acne rosacea",
      "couperose" and "facial erythrosis", in German also "Kupferfinne" and "Rotfinne".
      The disorder is characterised by a chronic and flaring course and is caused by a
      genetically predisposed, multifactorial process. A higher incidence is seen in
      people with fair skin and a positive family history. The characteristic rosacea
      symptoms manifest primarily, but not exclusively centrofacially, with forehead,
      nose, chin and cheeks significantly affected. Based on the various main symptoms
      a classification of the individual clinical pictures can be performed. However, a
      classification often does not reflect the clinical reality, since the various
      symptoms commonly coexist. The present review provides an introduction on
      pathogenesis and clinical manifestations of rosacea and prefers a symptom
      oriented therapy approach.

PMID- 27869373
TI  - Rosazea-Management: Update uber allgemeine Mabetanahmen und topische
      Therapieoptionen.
AB  - Obwohl bislang fur die Rosazea keine kurative Therapie besteht, konnen
      verschiedene Optionen zur Behandlung der Symptome und zur Vorbeugung von
      Exazerbationen empfohlen werden. Neben Selbsthilfemabetanahme wie der Vermeidung
      von Triggerfaktoren und einer geeigneten Hautpflege sollte das Rosazea-Management
      bei Patienten mit erythematoser und leichter bis schwerer papulopustuloser
      Rosazea die Anwendung topischer Praparate als First-Line-Therapie umfassen. Da
      Uberlappungen der charakteristischen Rosazea-Symptome im klinischen Alltag die
      Regel sind, sollte die medikamentose Therapie auf die individuellen Symptome
      zugeschnitten werden; auch eine Kombinationstherapie kann erforderlich sein. Zu
      den fur die Behandlung der Hauptsymptome der Rosazea zugelassenen Wirkstoffen
      gehoren Brimonidin gegen das Erythem sowie Ivermectin, Metronidazol oder
      Azelainsaure gegen entzundliche Lasionen. Ihre Wirksamkeit wurde in zahlreichen
      validen, gut kontrollierten Studien belegt. Daruber hinaus existieren
      verschiedene nicht zugelassene topische Behandlungsmoglichkeiten, deren
      Wirksamkeit und Sicherheit noch in grobetaeren, kontrollierten Studien zu
      untersuchen ist.

PMID- 27869374
TI  - State of the art: systemic rosacea management.
AB  - Based on numerous trials, oral tetracyclines and most commonly their second
      generation derivative doxycycline have become the main pillar in systemic rosacea
      treatment. However, the only preparation that has been approved so far in this
      setting is 40 mg doxycycline in an anti-inflammatory dosage and with a modified
      release formulation. With the introduction of this once-daily, non-antibiotic
      dosing of doxycycline, oral therapy is more commonly prescribed as first-line
      treatment in moderate to severe papulopustular rosacea. In addition, topical and
      oral strategies are often used in combination due to the more substantial
      improvements compared to monotherapy. Although several other non-approved oral
      agents like macrolides, isotretinoin, and carvedilol have been evaluated for
      systemic treatment and showed promising results, yet the experience with these
      drugs in rosacea is limited, and thus they should be reserved for special
      situations.

PMID- 27869375
TI  - Aktueller Stand der systemischen Rosazea-Therapie.
AB  - Basierend auf den Daten zahlreicher Studien sind orale Tetracycline - und hier
      insbesondere Doxycyclin als Tetracyclin der zweiten Generation - die Grundpfeiler
      der systemischen Rosazea-Therapie. Bisher ist dafur jedoch nur Doxycyclin 40 mg
      in antientzundlicher Dosierung mit veranderter Wirkstofffreisetzung zugelassen.
      Seit Einfuhrung der Therapie mit Doxycyclin einmal taglich in nicht
      antibiotischer Dosierung wird die orale Therapie haufiger als Erstbehandlung bei
      mittelschwerer bis schwerer papulopustuloser Rosazea verschrieben. Oft wird diese
      Behandlung aufgrund der besseren Wirksamkeit im Vergleich zur Monotherapie auch
      mit einer topischen Behandlung kombiniert. Obwohl in der Systemtherapie weitere,
      nicht zugelassene Wirkstoffe wie Makrolide, Isotretinoin und Carvedilol mit viel
      versprechenden Ergebnissen untersucht wurden, ist die vorliegende Erfahrung
      bisher begrenzt, so dass diese Substanzen speziellen Situationen vorbehalten
      bleiben sollten.

PMID- 27869376
TI  - Physikalische Methoden zur Behandlung der Rosazea.
AB  - Die Rosazea ist durch vielfaltige vaskulare Veranderungen gekennzeichnet. Neben
      Teleangiektasien und Erythemen treten haufig auch sogenannte "Flushings" auf.
      Haupteinsatzgebiete von Licht- und Lasersystemen sind diese vaskularen
      Veranderungen, wie Erytheme und Teleangiektasien. Neben dem KTP-Laser, dem
      Farbstofflaser (PDL) und dem Nd:YAG-Laser kommen auch Blitzlampen (IPL) zum
      Einsatz. Neben der Ruckbildung der vaskularen Komponente, ist auch eine
      Verbesserung der papulopustulosen Komponente beschrieben. Wahrend der KTP-Laser
      sehr gute Ergebnisse bei Teleangiektasien zeigt, werden der Farbstofflaser und
      die Blitzlampen bevorzugt bei flachigen Erythemen eingesetzt. Der ND:YAG-Laser
      kann bei Teleangiektasien und Erythemen eingesetzt werden, birgt aber von allen
      Systemen das nicht einschatzbare Narbenbildungsrisiko in sich. Die Bildung von
      Phymen stellt eine klinische Auspragung der Rosazea dar. Das am haufigsten
      vorkommende ist das Rhinophym. Bei moderaten und schweren Formen steht die
      Abtragung im Vordergrund. Die klassische chirurgische Abtragung stellt eine
      Moglichkeit zur Behandlung dar, haufig kommt es hierbei jedoch intraoperativ zu
      starkeren Blutungen. Alternativmethode ist die Elektrochirurgie und die
      Dermabrasion, wobei bei beiden Methoden Narbenbildungen auftreten konnen. Neuere
      Methoden wie die CO2 -Laserabtragung, eventuell in Kombination mit der Erbium:YAG
      Abtragung, stellen sichere und komplikationsarmere Varianten dar.

PMID- 27869377
TI  - Physical modalities for the treatment of rosacea.
AB  - Rosacea is characterised by a wide variety of vascular changes. Apart from
      telangiectasia and erythema, often so-called flushing occurs. These vascular
      abnormalities can be targeted with specific light and laser devices. In addition
      to KTP laser, pulsed dye laser (PDL) and Nd:YAG laser, also intense pulsed light
      devices (IPLs) are used. The described therapeutic effects include the reduction
      of vascular abnormalities and even improvement of papulopustular changes. While
      the KTP laser shows very good results in telangiectasia, the dye laser and IPL
      devices are used preferably in erythema. The Nd:YAG laser is also a possibility
      for patients with telangiectasia and erythema. However, compared to the other
      laser and light devices the Nd:YAG laser carries the highest risk of
      unpredictable scarring. Phymatous changes are another clinical manifestation of
      rosacea, mostly affecting the nose (rhinophyma). Moderate and severe cases are
      commonly treated with ablation modalities. Traditional surgery is a treatment
      option, but is often associated with major intraoperative bleeding. Alternative
      methods include electrosurgery and dermabrasion, although both methods can cause
      scarring. Newer methods such as CO2 laser ablation, possibly in combination with
      the erbium:YAG laser, are safe alternatives with a lower risk of complications.

PMID- 27869378
TI  - Pathogenese und Klinik der Rosazea als Schlussel fur eine symptomorientierte
      Therapie.
AB  - Rosazea ist eine haufige chronisch-entzundliche Hauterkrankung, die
      typischerweise bei Erwachsenen vorkommt und das Gesicht betrifft. Synonyme der
      Rosazea sind Acne rosacea, Kupferfinne, Rotfinne, Couperose und Rosacea. Die
      Erkrankung ist durch einen chronischen und schubartigen Verlauf gekennzeichnet
      und wird durch ein genetisch pradisponiertes, multifaktorielles Geschehen
      bedingt. Ein vermehrtes Auftreten wird bei hellem Hauttyp und positiver
      Familienanamnese verzeichnet. Die charakteristischen Rosazea-Symptome
      manifestieren sich vorwiegend, aber nicht ausschliebetalich zentrofazial, wobei
      Stirn, Nase, Kinn und die Wangen mabetageblich betroffen sind. Dabei werden
      unterschiedliche Hauptsymptome voneinander unterschieden, anhand derer eine
      Klassifikation der verschiedenen klinischen Bilder vorgenommen werden kann. Eine
      Klassifizierung wird oftmals jedoch nicht der klinischen Realitat gerecht, da die
      verschiedenen Symptome haufig gemeinsam auftreten. Diese Ubersichtarbeit fuhrt in
      die Pathogenese und Klinik der Rosazea ein und pladiert fur einen
      symptomorientierten Therapieansatz.

PMID- 27869380
TI  - ?

PMID- 27869379
TI  - Rosacea Management: Update on general measures and topical treatment options.
AB  - Although there is presently no cure for rosacea, there are several recommended
      treatment options available to control many of the symptoms and to prevent them
      from getting worse. In addition to self-help measures like avoidance of trigger
      factors and proper skin care, rosacea management should include topical
      medications as one of the first-line choices for patients with erythematous and
      mild to severe papulopustular rosacea. Since mixed forms of characteristic
      rosacea symptoms are more common, medical treatment must be symptom-tailored for
      each individual case and will often involve a combination therapy. Approved
      topical agents for the major symptoms of rosacea encompass brimonidine for
      erythema and ivermectin, metronidazole or azelaic acid for inflammatory lesions,
      all of which have shown their efficacy in numerous valid, well-controlled trials.
      In addition, there are several other, not approved topical treatments which are
      possible options that require further validation in larger well-controlled
      studies.

PMID- 27869381
TI  - [Analysis of adiposity and physical fitness in young Colombian students].
AB  - INTRODUCTION: Body mass index and physical fitness are important markers of a
      healthy life style. Objective: To analyze adiposity and physical fitness in young
      students from public schools in Armenia, Colombia, and examine differences
      between sex and age groups. Materials and methods: We analyzed 1,150 students:
      46.6% (n=536) males and 53.4% (n=614) females, with an age range of 10 to 20
      years (15.45 +/- 2.52). Physical fitness was evaluated by the Course-Navette
      test, the Horizontal Jump test, the 20-meter run test and the Sit-and-Reach test.
      Body mass index and body fat were also assessed. Results: Compared with males,
      females had significantly higher adiposity levels, body mass index (20.4 vs.
      19.5) and body fat (23% vs. 11%). Males had higher levels of physical fitness in
      all the variables analyzed, with statistically significant differences (p<0.001),
      except in flexibility, where females achieved better results (3.1cm vs.1 3cm;
      p=0.003). In both sexes, body mass index increased with age (p<0.001). However,
      body fat decreased with age in males (p<0.001) and increased in females
      (p<0.001). In males, physical fitness improved with age in all variables. In
      females, no significant differences were found between age groups except in the
      maximal oxygen uptake (VO2max, p<0.001). Conclusion: Adiposity was significantly
      higher in women than in men. Males had a better level of physical fitness than
      females, except in flexibility. Physical fitness improved significantly with age
      in males, but did not change in females.

PMID- 27869382
TI  - [Description of external cuticular setae of head, thorax, legs, abdomen and
      genitalia of four Triatominae species].
AB  - INTRODUCTION: The classification of the cuticular extensions of insects has been
      proposed as a taxonomic tool; however, the internal and external processes of the
      cuticular extensions of the Triatominae subfamily have not been fully analyzed
      and categorized. Objective: To describe the setae from different regions of the
      outer cuticle of several triatomine species by scanning electron microscopy.
      Materials and methods: Triatomines were washed and dried, after which different
      regions of the body from Eratyrus mucronatus, Triatoma maculata, Panstrongylus
      geniculatus and Belminus ferroae specimens were dissected, mounted on graphite
      double-sided adhesive tape over metal supports, metalized with gold and
      micrographed for further analysis. Results: We described nine types of cuticular
      setae. We found five types of setae in B. ferroae and T. maculata, four in P.
      geniculatus and only one in E. mucronatus. According to the proposed typology,
      type 3 seta was the most common in T. maculata, P. geniculatus and E. mucronatus,
      whereas type 1a predominated in B. ferroae. Conclusion: Type 3 seta was the most
      common in the Triatomini tribe (T. maculata, E mucronatus and P. geniculatus),
      whereas type 1a seta was specific to B. ferroae (tribe Bolboderini), suggesting
      that the surface morphology of the setae may have taxonomic value at tribe
      taxonomic level.

PMID- 27869384
TI  - [Atypical mucocutaneous manifestations in neonates and infants with chikungunya
      fever in the municipalities of Cucuta, Los Patios and Villa del Rosario, Norte de
      Santander, Colombia, 2014].
AB  - INTRODUCTION: Atypical clinical manifestations have been observed in newborns and
      infants suffering from fever caused by the chikungunya virus. Objective: To
      describe the cases of fever caused by the chikungunya virus in newborns and
      infants with atypical mucocutaneous lesions. Materials and methods: We reviewed
      the clinical records, as well as lab tests and histopathological results, of
      newborns and infants diagnosed with Chikungunya virus and atypical mucocutaneous
      lesions in three regional hospitals. Results: Out of 18 suspected cases of
      chikungunya virus in newborns and infants, 11 were positive and presented
      atypical mucocutaneous manifestations. Six of the eleven confirmed cases
      corresponded to children under five months of age. The most common symptoms were
      fever, skin rash, irritability, and diarrhea. Three of the patients were infected
      with both dengue and chikungunya viruses. The ulcers occurred in the scalp,
      abdomen, genital and perianal region. CONCLUSIONS: We report mucocutaneous
      manifestations in newborns and infants diagnosed with fever caused by the
      chikungunya virus in Colombia. The rapid development of ulcers is most likely due
      to the immune response to the virus. Special attention should be given to
      pregnant women presenting symptoms of chikungunya virus infection prior to
      delivery, and their offspring should be followed-up in order to monitor possible
      complications.

PMID- 27869383
TI  - [Geographic distribution of perinatal mortality due to congenital malformations
      in Colombia, 1999-2008: An analysis of vital statistics data].
AB  - INTRODUCTION: During 2012, 13% of the deaths worldwide in children under the age
      of 28 days were due to congenital malformations. In Colombia, congenital
      malformations are the second leading cause of infant mortality. Objective: To
      determine the geographical distribution of extended perinatal mortality due to
      congenital malformations in Colombia between 1999 and 2008. Materials and
      methods: We conducted a cross-sectional study. We revised all death certificates
      issued between 1999 and 2008. We defined perinatal mortality as fetal or non
      fetal deaths within the first 28 days after delivery in children with body weight
      >=500 grams, and congenital malformations according to ICD-10 diagnostic codes
      Q000 - Q999. The annual birth projection was used as the denominator. We defined
      high mortality areas due to congenital malformations as those in the 90th
      percentile. Results: We recorded 22,361 perinatal deaths due to congenital
      malformations. The following provinces exceeded the 90th perinatal mortality
      percentile: Antioquia, Caldas, Risaralda, Huila, Quindio, Bogota, Valle del Cauca
      and Guainia. Among the municipalities, the highest perinatal mortality rates were
      found in Giraldo, Ciudad Bolivar, Riosucio, Liborina, Supia, Alejandria,
      Sopetran, San Jeronimo, Santa Fe de Antioquia and Marmato (205.81 and 74.18 per
      10.000 live births).The perinatal mortality rate due to malformations of the
      circulatory system was 28.1 per 10.000 live births, whereas the rates for central
      nervous system defects and chromosomal abnormalities were 13.7 and 7.0,
      respectively. CONCLUSIONS: The Andean region showed high perinatal mortality
      rates due to congenital malformations. There is an urgent need to identify
      possible risk factors of perinatal mortality and implement successive prevention
      programs in that particular region.

PMID- 27869386
TI  - Prediction of the respiratory syncitial virus epidemic using climate variables in
      Bogota, D.C.
AB  - lntroduction: The respiratory syncitial virus is one of the most common causes of
      mortality in children and older adults in the world. Objective: To predict the
      initial week of outbreaks and to establish the most relevant climate variables
      using naive Bayes classifiers and receiver operating characteristic curves (ROC).
      Materials and methods: The initial dates of the outbreaks in children less than
      five years old for the period 2005-2010 were obtained for Bogota, Colombia. We
      selected the climatological variables using a correlation matrix and we
      constructed 1,020 models using different climatological variables and data from
      different weeks previous to the initial outbreak. In addition, we selected models
      using a six-year period (2005-2010), a four-year period (2005-2008), and a two
      year period (2009-2010). We obtained the best predictive models and the most
      relevant climatological variables to predict the outbreak using naive Bayes
      classifiers and ROC curves. Results: The best models were those using a two-year
      period (2009-2010) and week 0, with 52% and 60% of effectiveness, respectively.
      Humidity was the most frequent variable in the best models (62%). Conclusions: We
      used naive Bayes classifiers to establish the best models to predict correctly
      the initial week of the outbreak. Our results suggest that the best models used
      humidity, wind speed and minimum temperature in outbreaks prediction.

PMID- 27869385
TI  - [Phenotypic and molecular characterization of a Colombian family with
      phenylketonuria].
AB  - INTRODUCTION: Phenylketonuria is a metabolic disorder characterized by severe
      neurological involvement and behavioral disorder, whose early diagnosis enables
      an effective treatment to avoid disease sequelae, thus changing the prognosis.
      Objective: To characterize a family with phenylketonuria in Colombia at clinical,
      biochemical and molecular levels. Materials and methods: The population consisted
      of seven individuals of a consanguineous family with four children with
      suggestive symptoms of phenylketonuria. After signing an informed consent, blood
      and urine samples were taken for colorimetric tests and high performance liquid
      and thin layer chromatographies. DNA extraction and sequencing of the 13 exons of
      the PAH gene were performed in all subjects. We designed primers for each exon
      with the Primer 3 software using automatic sequencing equipment Abiprism 3100
      Avant. Sequences were analyzed using the SeqScape, v2.0, software. Results: We
      described the clinical and molecular characteristics of a Colombian family with
      phenylketonuria and confirmed the presence of the mutation c.398_401delATCA. We
      established a genotype-phenotype correlation, highlighting the interesting
      clinical variability found among the affected patients despite having the same
      mutation in all of them. Conclusions: Early recognition of this disease is very
      important to prevent its neurological and psychological sequelae, given that
      patients reach old age without diagnosis or proper management.

PMID- 27869387
TI  - [Trends in pertussis mortality and morbidity in Colombia, 2002-2012].
AB  - INTRODUCTION: Whooping cough is a public health problem that mainly affects
      children under one year of age with highly lethal outcomes. It is a re-emerging
      disease, which is preventable by immunization. Objective: To analyze mortality
      and morbidity trends of whooping cough in Colombia between 2002 and 2012.
      Materials and methods: We conducted a quantitative descriptive study of deaths by
      pertussis between 2002 and 2012 using data from death certificates registered by
      the Departamento Administrativo Nacional de Estadistica, and cases reported to
      the Sistema Nacional de Vigilancia en Salud Publica, 2005-2012. Frequency
      measurements, morbidity and mortality ratios and female increased mortality were
      calculated. Results: Fifty one point two percent of the deaths occurred in women;
      the year with more deaths was 2012; 67.3% occurred in urban areas, and 43.5% of
      the subjects were affiliated to the subsidized health regime. The risk of illness
      was 1.88 per 1,000 live births with increased risk in Vaupes and Vichada. The
      risk of death was 0.02 per 1,000 live births; there was a decrease in the
      lethality trend. Conclusions: Pertussis has reemerged with increasing mortality
      and morbidity. Since this is a preventable disease through vaccination, it is
      advisable to increase control and enhance vaccination coverage in both children
      and adults, who are an important reservoir of the disease. The effective control
      of pertussis demands continued work aimed at early identification. It is also
      necessary to carry out actions to improve data quality in order to facilitate its
      analysis and the generation of more valid information.

PMID- 27869388
TI  - [Cost-effectiveness of diagnostic strategies of severe bacterial infection in
      infants with fever without a source].
AB  - INTRODUCTION: Serious bacterial infections in infants under 2-years-of-age with
      fever without a source remains, despite advances in vaccination, a matter of
      concern for both physicians and parents. Having cost-effectiveness information is
      relevant to guide decision making in clinical practice in this scenario.
      Objective: To determine the cost-effectiveness of four different strategies of
      screening in Argentina for serious bacterial infection in children presenting
      with fever without a source. Materials and methods: We designed a decision tree
      to model a hypothetical cohort of 10,000 children with fever without a source. We
      compared the incremental cost-effectiveness of four strategies to detect serious
      bacterial infection: Rochester criteria + C reactive protein test, Rochester
      criteria + procalcitonin test, Rochester criteria, and expectant observation.
      Results: Rochester criteria + C reactive protein test was the most cost-effective
      strategy with USD$ 784 for each correctly diagnosed case versus USD$ 839 of
      Rochester criteria + procalcitonin test, USD$ 1,116 of expectant observation or
      USD$ 1,193 of Rochester criteria. When the probability of serious bacterial
      infections was equal or less than 14%, the strategy of choice was expectant
      observation. Conclusions: The Rochester criteria + C reactive protein test was
      the most cost-effective strategy to detect serious bacterial infection in one to
      three months old children with fever without a source. However, in low risk
      settings for such infection, the strategy of choice is expectant observation.

PMID- 27869389
TI  - [Suicide mortality in Colombia and Mexico: Trends and impact between 2000 and
      2013].
AB  - INTRODUCTION: Suicides are one of the main public health issues globally.
      Objective: To analyze the trends and impact of suicide mortality in Colombia and
      Mexico between 2000 and 2013, nationally, by sex and age groups. Materials and
      methods: Mortality vital statistics from the Colombian Departamento
      Administrativo Nacional de Estadistica and the Mexican Instituto Nacional de
      Estadistica y Geografia were used. We conducted a descriptive and cross sectional
      study for which we calculated standardized mortality rates and years of life lost
      in people between 0 and 100 years of age. Results: In Colombia, the suicide
      mortality rate decreased between 2000 and 2013 for both sexes (28% for men and
      38% for women); an opposite trend was observed in Mexico (with an increase of 34%
      for males and 67% for females). In 2013, the years of life lost in Colombia were
      0,32 among men and 0,15 among women, with a decreasing trend since 2000, whereas
      in Mexico a level of 0,42 was observed in men and 0,2 in women, with an
      increasing trend since 2000. The age groups where suicides had a bigger impact
      were those of men 15 to 49 years of age in both countries, while suicides were
      more uniformly distributed among women between 15 and 84 years of age.
      CONCLUSION:  Suicide mortality increased gradually in Mexico, whereas in Colombia
      an opposite trend was observed. Suicides can be prevented, so it is fundamental
      to implement public health policies focused on timely identification,
      comprehensive prevention strategies and the study of associated risk factors.

PMID- 27869390
TI  - [Factors related to treatment adherence in patients with tuberculosis in Pereira,
      Colombia, 2012-2013].
AB  - INTRODUCTION: According to the World Health Organization, the adherence to the
      tuberculosis treatment is the extent to which a patient's medication taking
      coincides with the prescribed treatment. The sum of cured patients and those who
      have completed treatment (directly observed therapy strategy, DOTS) are pragmatic
      indicators of the adherence. The patients who do not complete treatment
      correspond to non-adherents. Objective: To determine the relationship between
      anti-tuberculosis treatment adherence and socio-demographic, economic, clinical,
      and drug-related objective and subjective factors in patients over 18 years of
      age. Materials and methods: This was a descriptive, cross-sectional study of 174
      patient records of the tuberculosis control program and 15 semi-structured
      interviews to non-adherent patients during the period between June, 2012, and
      June, 2013. Results: The adherence in patients with pulmonary tuberculosis was
      94.8%. It was higher in patients in the social security contributory regime
      (p=0.035). Non-adherence was 5.2%. Drug intolerance was higher in the group of
      non-adherent patients. The lack of family support, absenteeism in the workplace,
      economic impact and dissatisfaction with the timeliness and the care of the
      health institution, were important in the decision of non-adherence. CONCLUSIONS:
      Affiliation to the health system regime and drug tolerance were objective factors
      related to adherence to treatment. The social and economic burden of disease is a
      subjective factor associated with the decision of not adhering to treatment.

PMID- 27869391
TI  - [First report of the F1534C mutation associated with cross-resistance to DDT and
      pyrethroids in Aedes aegypti from Colombia].
AB  - INTRODUCTION: The main strategy for the control of Aedes aegypti, vector of
      dengue, chikungunya and Zika viruses, is based on the use of insecticides to
      reduce its populations. However, their use has led to insect resistance to these
      chemicals. Objective: To determine the presence of the F1534C mutation associated
      with cross-resistance to DDT and pyrethroids in A. aegypti in Sincelejo,
      Colombia. Materials and methods: We studied nine specimens of A. aegypti that
      showed resistance to lambdacyhalothrin in bioassays developed by the Secretaria
      de Salud de Sucre. We used a semi-nested PCR as previously described by Harris,
      et al., to amplify exon 31 of the para gene of the voltage-dependent sodium
      channel of A. aegypti. We sequenced, edited, and analyzed PCR products with the
      MEGA 5 software. Results: We detected the wild and mutant alleles of exon 31 in
      all of the nine mosquitoes tested, and observed the substitution of thymine for
      guanine in the nucleotide sequence of the mutant allele, producing a change to
      UGC in the UUC codon, which led to the replacement of phenylalanine by cysteine
      in residue 1534 of the protein. Conclusion: The nine mosquitoes analyzed
      presented a heterozygote genotype for the F1534C mutation, whose phenotypic
      effect is knockdown resistance (kdr) to DDT and pyrethroids.

PMID- 27869392
TI  - [Detection of Aedes albopictus (Skuse) (Diptera: Culicidae) in the municipality
      of Istmina, Choco, Colombia].
AB  - INTRODUCTION: Aedes albopictus is widely distributed around the world. Its
      introduction to the Americas occurred in 1985 and it is considered a potential
      vector of dengue viruses and one of the principal vectors of chikungunya virus.
      In Colombia, this species was reported for the first time in Leticia (Amazonas)
      in 1998, followed by Buenaventura (Valle del Cauca) in 2001, Barrancabermeja
      (Santander) in 2010, and Medellin (Antioquia) in 2011. So far, this species has
      been reported in ten departments of the country. Objective: To report the finding
      of A. albopictus in the city of Istmina, Choco, and its implications for public
      health. Materials and methods: In January 2015, we conducted an inspection of
      immature stages of Aedes spp. in breeding sites in the neighborhoods of San
      Agustin, Santa Genoveva and Subestacion in Istmina, Choco. The immature stages
      collected in this municipality were identified at the Unidad de Entomologia of
      the Laboratorio de Salud Publica Departamental de Choco, and confirmed by the
      Laboratorio de Entomologia, Red Nacional de Laboratorios, Instituto Nacional de
      Salud, in Bogota. RESULTS: In January 2015, twelve A. albopictus larvae were
      found in the breeding sites located in Subestacion and San Agustin neighborhoods.
      CONCLUSIONS: The occurrence of A. albopictus in the municipality of Istmina
      underlines the importance of strengthening continuous entomological surveillance
      strategies at national and local levels in the country, especially in Istmina and
      its surrounding municipalities.

PMID- 27869393
TI  - [Assessment of the spatial accessibility to the rabies vaccination campaign in
      Bogota, Colombia].
AB  - INTRODUCTION: The access of Bogota's population to health services is unknown,
      and this hinders the planning of health prevention strategies. Objective: To
      estimate the spatial accessibility to the vaccination sites of the 2011 campaign
      against rabies in Bogota, Colombia, and to compare its efficiency with two other
      spatial coverage methodologies. Materials and methods: Spatial accessibility was
      determined using the two-step floating catchment area model (2SFCA). We
      calculated spatial coverage by establishing circular buffer zones using Euclidean
      distances, and irregular zones around the vaccination sites using Dijkstra's
      algorithm on the city's street network. Results: The spatial coverage of the
      program was 78.4% using the circular buffer zones, and 60.2% using Dijsktra's
      algorithm. The spatial accessibility analysis revealed that the periphery of the
      city had the lowest accessibility to the program. This peripheral area is a very
      critical zone because it is an urban-rural interface, which represents a risk for
      the re-introduction of rabies in the city. Conclusions: The 2SFCA spatial
      accessibility model is an effective tool to identify isolated areas, evaluate
      health services use more precisely, and provide basis for their strategic
      location. We concluded that this approach had the potential to improve resource
      efficiency when planning rabies control programs in urban environments such as
      Bogota. The findings emphasize the need for surveillance and intervention in
      isolated areas with low access to services.

PMID- 27869394
TI  - [Recommendations for the surveillance of Aedes aegypti].
AB  - Diseases caused by arboviruses transmitted by Aedes aegypti, such as dengue,
      chikungunya and Zika, continue to rise in annual incidence and geographic
      expansion. A key limitation for achieving control of A. aegypti has been the lack
      of effective tools for monitoring its population, and thus determine what control
      measures actually work. Surveillance of A. aegypti has been based mainly on
      immature indexes, but they bear little relation to the number of mosquito
      females, which are the ones capable of transmitting the viruses. The recent
      development of sampling techniques for adults of this vector species promises to
      facilitate surveillance and control activities. In this review, we present the
      various monitoring techniques for this mosquito, along with a discussion of their
      usefulness, and recommendations for improved entomological surveillance.

PMID- 27869396
TI  - [Real-time quantification to analyze historical Colombian samples detecting a
      short fragment of hypervariable region II of mitochondrial DNA].
AB  - INTRODUCTION: Unlike other molecular biology studies, the analysis of ancient DNA
      (aDNA) requires special infrastructure and methodological conditions to guarantee
      the quality of the results. One of the main authenticity criteria is DNA
      quantification, where quantitative real-time PCR is often used given its
      sensitivity and specificity. Nevertheless, the implementation of these conditions
      and methodologies to fulfill authenticity criteria imply higher costs. Objective:
      To develop a simple and less costly method for mitochondrial DNA quantification
      suitable for highly degraded samples. Materials and methods: The proposed method
      is based on the use of mini-primers for the specific amplification of short
      fragments of mitochondrial DNA. The subsequent purification of these amplified
      fragments allows a standard curve to be constructed with concentrations in
      accordance to the state of degradation of the samples. Results: The proposed
      method successfully detected DNA from ancient samples including bone remains and
      mummified tissue. DNA inhibitory substances were also detected. Conclusion: The
      proposed method represents a simpler and cost-effective way to detect low amounts
      of aDNA, and a tool to differentiate DNA-free samples from samples with
      inhibitory substances.

PMID- 27869395
TI  - [Allergen immunotherapy: Mechanisms of action, and therapeutic and socioeconomic
      impact Consensus of the Asociacion Colombiana de Alergia, Asma e Imunologia].
AB  - Allergies comprise a set of highly prevalent diseases. When allergic processes
      are not controlled, they can endanger patients' health and lives, and have an
      important economic and social impact. The aim of this paper is to present a
      practical consensus of the scientific evidence on the use of immunotherapy in
      allergic diseases. A collaborative review made by various institutes and
      universities in Colombia was carried out upon request of the Asociacion
      Colombiana de Alergia, Asma e Imunologia, led by general practitioners,
      allergists, immunologists, internists and paediatricians with experience in the
      field of allergies. As a result, based on current national and international
      scientific evidence, we describe in detail what immunotherapy is about, its
      indications, contraindications and its economic and health benefits. Conclusions
      show immunotherapy as a clinically effective and safe treatment, which can
      substantially reduce the cost of the overall treatment of allergic patients.

PMID- 27869398
TI  - ?

PMID- 27869397
TI  - ?

PMID- 27869399
TI  - ?

PMID- 27869400
TI  - ?

PMID- 27869401
TI  - Yersiniosis in Poland in 2014
AB  - OBJECTIVE: The aim of the study is to present the epidemiological situation of
      yersiniosis in Poland in 2014 and compare it with the situation in the previous
      years. MATERIAL AND METHODS: The evaluation was based on analysis of data from
      the annual bulletins "Infectious diseases and poisoning in Poland" for the period
      2009-2014 (MP Czarkowski et al., National Institute of Hygiene and GIS - Chief
      Sanitary Inspectorate), interviews of individual yersiniosis cases, sent by the
      sanitary-epidemiological stations from the whole country and the data on deaths
      from the Department of Demographic Studies of the Central Statistical Office.
      RESULTS: In 2014 in Poland 244 cases of yersiniosis were recorded (0.63/100 000).
      Among them 241 infections were caused by Y. enterocolitica and 3 by Y.
      pseudotuberculosis. There were 215 cases of intestinal yersiniosis and 29 of
      extraintestinal. Hospitalization required 59.8% of patients. There were no deaths
      reported which cause was infection with Yersinia. Intestinal yersiniosis was
      manifested the mostly by symptoms as follow: diarrhea (88%, including 8% with
      blood in stool), fever (66%), abdominal pain (49%) and vomiting (22%). The most
      of the cases (131 - approx. 61%) of intestinal yersiniosis occurred among
      children in the age group 0-4 years . Number of extra intestinal Yersinia
      infections (20 cases) was higher than in 2013. The most frequent symptom of those
      cases was osteoarticular pain, which was observed in 79% of patients. As in 2013
      most cases of intestinal yersiniosis  were reported from the Mazowieckie
      voivodeship (104 cases). Serological type of Yersinia was determined only in 58
      (24%) cases. This percentage was the lowest since the start of registration of
      yersiniosis in the country in the year 2006. The identified serotypes were O3
      (88%) O8 (6.9%) and O9 (5.2%). In 2014, 4 cases of infection with "American"
      serotype O8 were identify. One family outbreak caused by Yersinia spp occurred in
      2014. CONCLUSIONS: A significant decrease of serologically identified cases of
      yersinia observed in 2014. could be explained by the test for Yersinia not being
      reimbursed by routine health care insurance. Reporting cases of extraintestinal
      yersiniosis from only few voivodeships suggests that the real number of
      infections remains underreported. In 2014 significantly higher number of cases of
      Yersinia infection occurred during the second and third quarter of the year.
      Seasonality of yersiniosis in 2014 differs from seasonality in 2013. However, it
      was similar to the seasonality observed in previous years (2009-2012).

PMID- 27869402
TI  - Stem cell transfer in newborn infants through placental transfusion via delayed
      umbilical cord clamping.

PMID- 27869403
TI  - Community-acquired Staphylococcus aureus, a recent problem.

PMID- 27869404
TI  - Being a doctor, being human.

PMID- 27869405
TI  - An attempt to include happiness within the psychiatric disorders.

PMID- 27869406
TI  - BRUE: a new term and approach that could improve our practice.

PMID- 27869407
TI  - Community-acquired Staphylococcus aureus bacteremia in children: a cohort study
      for 2010-2014.
AB  - INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus
      infections are a common, serious problem in pediatrics. OBJETIVE: To describe
      antibiotic resistance in community-acquired Staphylococcus aureus (SA)
      bacteremias. To compare the characteristics of SA bacteremias in terms of
      methicillin resistance. MATERIALS AND METHODS: Prospective cohort enrolled
      between January 2010 and December 2014. Inclusion criteria: infants and children
      between 30 days old and 16 years old hospitalized at the Hospital de Pediatria J.
      P. Garrahan due to community-acquired infections with SA growth identification in
      blood cultures. Exclusion criteria: having a history of recent hospitalization,
      attending a health care facility, living in a closed community, or having a
      venous catheter. Microbiological, demographic, and clinical characteristics were
      compared in terms of methicillin susceptibility. Statistical analysis: Stata10.
      RESULTS: A total of 208 children were included; boys: 141 (68%). Their median age
      was 60 months old (interquartile range: 29-130). Thirty-four patients (16%) had
      an underlying disease. Methicillin-resistant Staphylococcus aureus was identified
      in 136 children (65%). The rate of resistance to clindamycin was 9%. Significant
      statistical differences were observed in the rate of underlying disease,
      persistent bacteremia, sepsis at the time of admission, secondary source of
      infection, admission to the intensive care unit, and surgery requirement. Twelve
      patients (6%) died; community-acquired methicillin-resistant Staphylococcus
      aureus was identified in all of them. CONCLUSIONS: In the studied cohort,
      methicillin-resistant S taphylococcus aureus was predominant. The rate of
      resistance to clindamycin was 9%. Community-acquired methicillin-resistant
      Staphylococcus aureus infections prevailed among healthy children. Among patients
      with methicillin-resistant Staphylococcus aureus infections there was a higher
      rate of persistent bacteremia, admission to the ICU and surgery.

PMID- 27869409
TI  - Communication skills of residents to families with Down syndrome babies.
AB  - BACKGROUND: Generally, pediatricians are the first health caregivers to deliver
      initial diagnosis of Down syndrome (DS) to the families. However, most of the
      parents are not satisfied with the contents and how they receive information when
      their child is born with DS. Pediatric residents should target educational
      interventions to help parents to overcome with these issues and to provide
      accurate information. The objective is to assess comfort levels and training
      requirements of pediatric residents to communicate with parents of babies born
      with Down syndrome. METHODS: Diagnostic Situations Inventory (DSI) is a rating
      scale which included ten questions to assess discomfort level. A survey was sent
      via mobile, websites and all the social media which were available to all
      pediatrics residents in the country. Socio-demographic factors including
      information about training requirement were collected as well. RESULTS: From the
      326 participants, total mean discomfort level was 30.22 in DSI out of 50 which
      was the highest score. Discomfort level was significantly increased in female
      participants (p= 0.033). Being female (p= 0.014), having less residency level (p=
      0.028), examining less number of patients with Down syndrome (p= 0.025) and
      having higher discomfort levels (p= 0.001) were found to be related with
      increased training requirement. From the residents, 84% declared the need for
      additional training. CONCLUSIONS: This study showed that pediatric residents had
      a high level of discomfort when communicating with parentes of newborn with Down
      Syndrome. Female residentes had a discomfort level significantly higher than male
      residentes.

PMID- 27869408
TI  - Knowledge level, attitude and own experience of health professionals about
      breastfeeding and breast milk in a city of Turkey: Cross-sectional study.
AB  - INTRODUCTION: Worldwide consensus about breastfeeding is that the infant should
      exclusively be breastfed until six months of life. Despite this, the rate of
      exclusive breastfeeding for the first six months of age is low in so many
      countries including Turkey. The aim of this study was to evaluate the knowledge,
      the attitudes and the own experiences of health professionals about breastfeeding
      and breast milk, in a metropolitan city in Turkey. MATERIALS AND METHODS: This
      study was performed between July 2012 and December 2013. Study subjects included
      healthprofessionals working in the university hospitals, research and training
      hospitals, public and private hospitals; child, adolescent, women and
      reproductive health services centers, family health centers, and community health
      centers located in Ankara. A questionnaire was used to collect data. SPSS 11.5
      package program was used for statistical analysis. RESULTS: A total of 715 people
      participated in this study. From those who had children themselves 3.4% (n= 16)
      had not breastfed their babies at all, and 7.6% (n= 36) had breastfed their baby
      until second year of age. It was found that 28.4% of the participants had poor,
      43.1% had average and 28.5% had good knowledge level about breastfeeding and
      breast milk. CONCLUSION: This study reflects the lack of knowledge about
      breastfeeding and breast milk among the health professionals in Turkey. Although
      a great majority of participants agree the recommendation of WHO about the
      duration ofbreastfeeding, the percentage ofbreastfeeding of health care
      professionals during recommended period was very low.

PMID- 27869410
TI  - The effect of strength training based on process approach intervention on balance
      of children with developmental coordination disorder.
AB  - INTRODUCTION: Balance is one of the main problems of children with developmental
      coordination disorder (DCD). According to process-oriented approach, besides
      strength training, neuromuscular adaptations can improve balance. OBJETIVE: To
      evaluate the effects of strength training on improving static and dynamic balance
      in DCD children. METHODS AND POPULATION: Children between 7 to 9 years old in
      Tehran participated in the study through randomized controlled trial design.
      Subjects were randomly divided into two experimental (n = 15) and control (n= 15)
      groups. The participants exercised for 12 weeks and 24 sessions. The experimental
      group received strength training using flexible Thera-band elastic exercise and
      control group received routine exercises in physical education class. Isometric
      strength of hip abductor muscles and plantar flexors were measured using hand
      held dynamometer, and Bruininks-Oseretsky Test of Motor Proficiency, Second
      Edition (BOT-2) was used for measurement of static and dynamic balance. Data were
      analyzed using independent and paired sample t-tests. RESULTS: Strength training
      significantly increased muscle strength in DCD children (P <0.001) and improved
      their static balance performance (P <0.05); however, these exercises had no
      significant effect on their dynamic balance performance (P >0.05). CONCLUSIONS:
      The strength training leads to static balance improve in DCD children. There was
      not an improvement in dynamic balance through the strength training in these
      children.

PMID- 27869411
TI  - Analysis of spatial-temporal clusters of childhood cancer incidence in the
      province of Cordoba, Argentina (2004-2013).
AB  - INTRODUCTION: In spite of its low incidence, childhood cancer is becoming
      increasingly more relevant in Argentina. More advances have been made in cancer
      treatment than in the study of its etiology or determining factors. There are no
      investigations that analyze its spatial and temporal distribution or potential
      clustering. OBJETIVE: To perform exploratory spatial and temporal analyses based
      on the database of the Registry of Tumors of the Province of Cordoba (2004-2013)
      to determine the clustering of childhood cancer incidence in Cordoba (Argentina).
      POPULATIONS AND METHODS: Epidemiological, retrospective, ecological study. Data
      from 1098 patients with malignancies aged 0-14 years old from the Registry of
      Tumors of the Province of Cordoba (2004-2013) were used. A geographic information
      system model was developed. The presence of spatial, temporal, and spatial
      temporal clusters was analyzed in the districts of Cordoba using the SaTScan
      software. RESULTS: Spatial clusters were detected, with a high number of cases,
      for total tumors (p= 0.01), leukemias (p= 0.02), malignant neoplasms of lymphoid,
      hematopoietic and related tissue (p= 0.03), central nervous system tumors (p=
      0.03), and a high level of indicators of risk for renal tumors (p= 0.01). In
      addition, a temporal cluster (p= 0.01) and a spatial-temporal cluster (p= 0.02)
      for neuroblastoma and other peripheral nervous cell tumors were also observed.
      CONCLUSIONS: Significant clusters were determined, with important associated
      indicators observed in several districts of Cordoba. This is the first
      methodological step towards the development of new investigations on the risk
      factors for childhood cancer and its etiology.

PMID- 27869412
TI  - Blood lead levels in children aged between 1 and 6 years old in La Plata,
      Argentina. Identification of risk factors for lead exposure.
AB  - INTRODUCTION: Lead has neurotoxic effects in children, even at a very low level
      in blood. The risk factors (RFs) for lead exposure have not been adequately
      identified in La Plata. The objectives of this study were to determine mean blood
      lead levels and identify RFs in children aged 1 to 6 years old living in La Plata
      and the outskirts. POPULATION AND METHODS: A cross-sectional study was conducted
      in children who attended primary health care centers for a health check-up. Blood
      lead levels were determined by atomic absorption spectroscopy, and a
      socioenvironmental survey was administered to outline RFs. The Mann-Whitney test
      was used to compare measurements. A multivariate statistical analysis was done to
      establish the most relevant RFs. RESULTS: A total of 319 children participated
      (51% were boys); the median (interquartile range) blood lead level was 2.2 pg/dL
      (1.1-3.6 pg/dL). Significant mean differences in blood lead levels were observed
      for age<= 3years old, anemia, pica behavior, overcrowding, dirt floors, and
      maternal education < 7 years. Age<= 3years old and pica behavior were both RFs
      with significant odds ratios (ORs). The OR as adjusted by logistic regression was
      significant only for age<= 3years old. CONCLUSIONS: The median blood lead level
      in the studied population was 2.2 pg/dL. The main RFs identified for lead
      exposure were age<= 3years old and pica behavior. Other less relevant RFs
      included anemia, maternal education < 7 years, overcrowding, and dirt floors.

PMID- 27869413
TI  - Humoral immunity to tetanus, measles and rubella in children with acute
      lymphoblastic leukemia after chemotherapy.
AB  - Chemotherapy regimens and clinical support advances have improved survival in
      children with acute lymphoblastic leukemia. The after-effects of treatment are a
      reason for concern, including damage to the immune system induced by
      immunosuppressive therapy which is reflected in the loss of antibody protection
      provided by prior immunizations. Our goal was to assess the presence of measles,
      rubella, and tetanus protective antibody titers among patients with acute
      lymphoblastic leukemia after completing chemotherapy. Sixty-one children with
      acute lymphoblastic leukemia seen at the Hospital Garrahan were included;
      patients had finished their chemotherapy at least 6 months earlier and had a
      complete immunization schedule before diagnosis. The rates of protective
      antibodies were 46% (CI: 32-59) for measles, 53% (CI 40-67) for tetanus, and 60%
      (CI 47-63) for rubella. These results strengthen the need to reconsider
      revaccination in this group of patients.

PMID- 27869414
TI  - Prevalence and clinical course of typical hemolytic uremic syndrome among
      sibling.
AB  - Introduction: Hemolytic uremic syndrome (HUS) isaninfectious disease caused by
      Shiga toxin-producing Escherichia coli. The objective of this study was to assess
      the risk of transmission and clinical course between siblings with typical HUS.
      Population and methods: Medical records of children with typical HUS between 1997
      and 2012 were reviewed. Sibling pairs were established as inclusion criteria. A
      severity score was defined. Results: A total of 133 patients with HUS were
      recorded; 40 had siblings and 4 progressed to HUS (10%). The mean age of the 4
      sibling pairs was 29.3 months old (SD +/- 11.5); 5 (62.5%) were girls. The mean
      time between each case was 5.7 days (SD +/- 3). HUS was more severe in the
      siblings who became infected in the second place. Conclusion: The risk of HUS
      transmission between siblings was 10%, and the clinical course of the second
      sibling was less favorable.

PMID- 27869415
TI  - A new challenge for the world: the eradication of polio.
AB  - Poliovirus infects 100% of susceptible individuals and causes acute flaccid
      paralysis in one out of200 infections. Type 1 causes epidemic poliomyelitis; type
      2 has been eradicated worldwide; and type 3 is close to being eradicated. In this
      region, the last case of wild poliovirus occurred in Peru in 1991. There are
      still two endemic countries: Afghanistan and Pakistan, but countries where there
      is no circulation of the wild poliovirus have also reported imported cases of
      polio. In May 2012, the World Health Assembly declared the polio eradication a
      programmatic emergency for global public health and, as a result, developed the
      Polio Eradication and Endgame Strategic Plan 2013-2018. The Plan has four
      objectives: 1) Detect and interrupt all poliovirus transmission and maintain
      surveillance of acute flaccid paralysis in children < 15 years. 2) Strengthen
      immunization systems and withdraw oral polio vaccine by the first trimester of
      2016. Replace the trivalent oral polio vaccine with the bivalent oral vaccine,
      containing serotypes 1 and 3, and introduce the inactivated polio vaccine in all
      immunization schedules to maintain immunity against poliovirus type 2. 3) Contain
      poliovirus and certify interruption of transmission. 4) Plan the exploitation of
      the fight against polio and its impact on public health. The plan is expected to
      reach its goals by 2018; all use of the oral polio vaccine will be interrupted
      thereafter. Change in immunization schedules will require pediatricians to
      provide advice and guidance to families depending on the varied situations of
      everyday practice.

PMID- 27869416
TI  - Non-alcoholic fatty liver disease: a new epidemic in children.
AB  - Non-alcoholic fatty liver disease is considered one of the most common causes of
      liver disease in adults and children, consistent with the increased prevalence of
      obesity in both populations worldwide. It is a multifactorial condition involving
      a broad spectrum of liver diseases than range from simple steatosis to
      steatohepatitis, and characterized by histological findings of inflammation and
      fibrosis. Its pathogenesis and progression are not fully understood yet, and a
      more complete understanding of liver disease may aid in developing new therapies
      and noninvasive diagnostic tools. Liver biopsy remains the gold standard for
      disease staging. Although lifestyle and diet modifications are the keys in non
      alcoholic fatty liver disease treatment, the development of new drugs may be
      promising for patients failing first-line therapy.

PMID- 27869417
TI  - Micronutrients and neurodevelopment: An update.
AB  - Micronutrients make up the central nervous system structure and play major
      functional roles: they stimulate nerve cell development, migration, and
      differentiation. The goal of this study is to review the scientific literature
      regarding the role of micronutrients in infant brain structure and function.
      Thus, we aim at providing pediatricians with knowledge on the importance of
      introducing all nutrients into the diet based on breast milk composition. The
      following databases were reviewed: MEDLINE, through PubMed, TRIP Database, and
      LILACS. An adequate nutrient supply, including calcium, copper, choline, iron,
      folic acid, iodine, and vitamins during pregnancy and lactation and in
      complementary feeding will have an effect on brain development and/or function.

PMID- 27869418
TI  - [Mastitis update.]

PMID- 27869419
TI  - [Klippel-Feil syndrome with tracheoesophageal fistula, bifid thumb and cerebral
      angiolipoma.]
AB  - The Klippel-Feil syndrome is a congenital malformation of the skull flap
      involving complex cervical vertebrae and organs, characterized by a classic
      triad: short neck, limitation of movement of the head due to cervical spine
      fusion and low hairline in occipital region. It results from an error in the
      axial skeleton segmentation of the embryo; its incidence is estimated at 1/40,000
      42,000 births and predominates in females. The aim of this paper is to describe
      the clinical picture of a patient with Klippel-Feil syndrome and multiple
      malformations, including tracheoesophageal fistula, bifid thumb and intracranial
      lipomas/angiolipomas,that have not been previously described in the syndrome, so
      it is considered an exceptional finding.

PMID- 27869421
TI  - [Gestational alloimmune liver disease: a case report].
AB  - Gestational alloimmune liver disease, previously known as neonatal
      hemochromatosis, is characterized by severe liver disease in neonatal period,
      associated with intra and extrahepatic iron accumulation. It is postulated an
      alloimmune origin, which has opened new opportunities in the treatment and
      prevention during risk pregnancies, changing the prognosis of this pathology. We
      report the case of a newborn that presents early liver failure, with clinical and
      analytical features compatible with gestational alloimmune liver disease.
      Exchange transfusion was made and gamma globulins were given, with good clinical
      evolution.

PMID- 27869420
TI  - Trichorhinophalangeal syndrome type II presenting with short stature in a child.
AB  - Trichorhinophalangeal syndrome type II (TRPSII) (synonym: Langer-Giedon syndrome)
      is a rare autosomal dominant contiguous gene syndrome, resulting from a
      microdeletion encompassing the EXT1 and the TRPS1 gene at 8q24 (MIM#150230). This
      syndrome combines the clinical features of two autosomal dominant disorders,
      trichorhinophalangeal syndrome type I (MIM#190350) and hereditary multiple
      osteochondromas type I (MIM # 133700). TRPSII is characterized by sparse scalp
      hair, a long nose with a bulbous tip, long flat philtrum, cone-shaped epiphyses
      of the phalanges, retarded bone age in infancy and multiple cartilaginous
      osteochondromas. We report a Turkish patient who had the clinical features and
      skeletal signs of TRPSII in whom a 13.8Mb deletion in 8q23.1- 8q24.13 was
      detected.

PMID- 27869422
TI  - [Scorpionism in children in Tucuman: descriptive analysis of cases in a second
      level of complexity Hospital].
AB  - Scorpionism in Tucuman is very frequent. The aim is to describe the clinical and
      epidemiological characteristics of cases of scorpionism that were seen in the
      Emergency Department of Eva Peron Hospital, Banda del Rio Sali, Tucuman, between
      July 2013 and March 2015. Forty patients were assisted, 21 boys and 19 girls. The
      average age was 6.89 years. Thirty four (85%) resultedmild, 3 (7.5%) moderated, 3
      (7.5%) moderated-severe. Hands (22.6%) and feet (20%) were the places in the body
      where the stings were more frequently localized. In only 3 cases the scorpion
      could be identified as Tityus trivittatus. Six (the moderate and moderate-severe
      cases) patients received specific antidote, with variable response. Although most
      of the cases were mild, this is an entity with severe prognosis in some patients.
      Epidemiological surveillance is necessary to arrange prevention measures, as we
      do in this Hospital.

PMID- 27869423
TI  - [Progressive moderate mitral regurgitation in a children with Axenfeld-Rieger
      syndrome. The importance of cardiologic follow up].
AB  - Axenfeld-Rieger syndrome is a congenital disease with an estimated prevalence of
      one in 200,000 individuals. This is an ophthalmic disorder related to anterior
      segment dysgenesis, which may be present from the neonatal period. It is
      associated with extraocular affectations such as cranial dimorphism,
      maxillofacial or dental anomalies. Cardiological or pituitary manifestations are
      less common. The congenital heart disease in Axenfeld-Rieger syndrome has been
      described in very few cases in the literature. We report a 7-year-old patient
      with Axenfeld-Rieger syndrome and mild mitral insufficiency since the age of 3
      years, which is progressing to moderate mitral regurgitation at the present time.
      The cardiologic follow up may be indicated in patients with Axenfeld-Rieger
      syndrome.

PMID- 27869424
TI  - [Study of Medullary Thyroid Carcinoma from a proband].
AB  - Thyroid cancer is an uncommon type of cancer, accounting less than 1% of all
      cancers in adults, and 0.5-3% of all cancers in children. There are four
      different types: papillary carcinoma (80-90% of cases), follicular (5-10%),
      medullary (5%) and anaplastic cell (2-3%). Eighty per cent of cases of medullary
      thyroid cancer are sporadic, but 20% are associated with an inherited syndrome
      that is divided into three groups: multiple endocrine neoplasia type 1, multiple
      endocrine neoplasia type 2 and familial medullary thyroid carcinoma. The
      inherited forms are caused by a disruption in the RET oncogene, which is located
      in the long arm of chromosome 10. A hereditary case of medullary thyroid
      carcinoma is presented. It was detected because of a familial genetic study. The
      purpose of the paper is emphasize the importance of the early diagnosis and the
      intervention of multidisciplinary teams of experts.

PMID- 27869425
TI  - Isolated omental panniculitis in a child with abdominal pain: case report.
AB  - Isolated omental panniculitis is a rare entity mostly seen in adults. It presents
      with the inflammation of the fatty tissue of the omentum. The symptoms may vary
      from local (e.g. abdominal tenderness or palpable mass) to systemic
      manifestations including abdominal pain, back pain, fever, weight loss and bowel
      disturbances. We presented this case as a first awareness of omental panniculitis
      in a child which must be kept in mind at the differential diagnosis of ileus so
      that unnecessary surgeries might be avoided.

PMID- 27869426
TI  - An umbilical venous catheter complication presented as acute abdomen: case
      report.
AB  - Umbilical venous catheterization has become a widely accepted intravenous route
      for premature babies. These catheters allow administration of parenteral
      nutrition and medication and facilitate blood sampling. Besides these benefits,
      they also have significant potential complications like portal vein thrombosis,
      infection, vascular or hepatic injury, arrhythmia and sepsis. One of the rare but
      important complication is extravasation of the fluids due to misplacement of the
      catheter. The typical symptoms of this condition are sudden deterioration,
      hepatic enlargement, hematocrit drop, hypotension and abdominal distension. We
      herein present a premature newborn with unusual acute abdomen findings suggesting
      a surgical pathology after the extravasation of total parenteral nutrition into
      the abdomen.

PMID- 27869427
TI  - Vancomycin-resistant Enterococcus bacteremia in a child with acute myeloid
      leukemia: successful treatment with daptomycin.
AB  - Multiple-drug-resistant enterococcal infections canbe a serious problem in
      pediatric patients particularly concomitance with severe underlying diseases and
      lead to significant morbidity and mortality. The treatment options in children
      are limited compared with adults. We report a 3-year old-boy with acute myeloid
      leukemia (AML)-M7 and vancomycin-resistant enterococcus bacteremia successfully
      treated with daptomycin. Daptomycin may be an alternative therapy for VRE
      infections in children; more studies are needed for extended usage.

PMID- 27869428
TI  - [Hemolytic anemia as the first clinical presentation of Wilson disease: a
      pediatric case].
AB  - : Wilson disease is an autosomal recessive disorder of the copper's hepatic
      metabolism; it results in toxicity due to accumulation of the mineral. The
      hemolytic anemia is present in 17% at some point of the disease, although it is a
      rare initial clinical presentation. CASE REPORT: 11 years old boy who presented
      with negative Coombs hemolytic anemia and elevation of liver enzymes. The
      possibility of Wilson disease was considered, which was confirmed with the
      finding of a Kayser-Fleischer ring in the eye exam. He also had a low
      ceruloplasmin level in plasma and a high urinary copper excretion. He was treated
      with D-penicillamine and pyridoxine.

PMID- 27869429
TI  - [Topical corticosteroids as a therapeutic alternative in linear immunoglobulin A
      bullous dermatosis in childhood: case report].
AB  - Linear immunoglobulin A dermatosis of childhood is a rare autoimmune disorder.
      Its etiology remains unknown, although it has been linked to drugs, infections,
      immunological diseases and lymphoproliferative processes. We report the case of a
      6 year old girl who consulted for perioral bullous lesions without other
      symptoms. Neither treatment with mupirocin nor methylprednisolone therapy
      achieved remission of cutaneous lesions. Skin biopsy showed a linear
      immunoglobulin A dermatosis. It was not possible to start treatment with dapsone
      because of a partial glucose-6-phosphate dehydrogenase deficiency, so topical
      treatment was maintained with good evolution of lesions. Linear immunoglobulin A
      dermatosis is a rare disease whose differential diagnosis includes other bullous
      diseases. Pathology is essential for diagnosis. When treatment with dapsone is
      not possible, topical corticosteroids may be an alternative, either alone or
      associated with other treatments.

PMID- 27869430
TI  - [Sepsis due to Pseudomona as a debut of a primary immunodeficiency in a child].
AB  - X-linked agammaglobulinemia is a primary humoral immunodeficiency. It is a
      recessive X-linked disorder characterized by low or absent circulating mature B
      cells, hypo/agammaglobulinemia and no humoral response to immunizations due to
      mutations along chromosome X. It is characterized by severe, recurrent and
      difficult treatment infections. It is diagnosed in the first 6 months of life in
      children; the only sign of alarm is the absent or decreased size of tonsils and
      lymph nodes, but it is not always present. The main cornerstones of treatment are
      immunoglobulin replacement therapy to maintain serum levels above 500-700 mg/dl
      and infection control; this allows these patients to do their day-to-day
      activities. We report a 2 year old boy with X-linked agammaglobulinemia, with no
      history of interest, who presented with P. aeruginosa sepsis. He had an excellent
      clinical improvement without further important infections after intravenous
      immunoglobulin replacement therapy.

PMID- 27869431
TI  - [Deletion on the short arm of chromosome 18 syndrome diagnosed by array
      comparative genomic hybridization. Presentation of one case with a mild
      phenotype].
AB  - Deletion on the short arm of chromosome 18 is an infrequent syndrome and it is
      characterized by the following features: mental retardation, growth retardation,
      craniofacial malformations such as large ears, microcephaly, and short neck. The
      phenotypical spectrum is a wide range of abnormalities including minor congenital
      abnormalities to holoprosencephaly. We present a case of a 10 year old girl who
      is found to have a deletion on the short arm of chromosome 18 (18p11.32-p11.21),
      by conventional cytogenetic analysis and comparative genomic hybridization.

PMID- 27869432
TI  - [Massive hydrothorax in a ease of hemolytic uremic syndrome: conservative
      treatment without interruption of peritoneal dialysis].
AB  - : The hydrothorax is a known but rare complication of acute and chronic
      peritoneal dialysis. Patients with hemolytic uremic syndrome seem to be more
      prone to this complication. Usually discontinuation of treatment is necessary due
      to the lack of resolution or recurrence of hydrothorax and transfer to
      hemodialysis, but some patients can continue dialysis with modification of
      technique and with resolution of hydrothorax. CASE REPORT: a child with hemolytic
      uremic syndrome presented a massive hydrothorax during acute peritoneal dialysis
      which resolved with dialysis schema modification without interruption of
      treatment.

PMID- 27869433
TI  - [Conservative management of tracheal rupture in a child after blunt trauma].
AB  - La rotura traqueal tras una contusion es rara, aunque potencialmente mortal. En
      general, se recomienda el tratamiento quirurgico para la rotura traqueal, aunque
      tambien se ha informado recientemente el abordaje conservador en los pacientes
      con signos vitales y parametros respiratorios estables. El objetivo de este
      estudio es informar sobre un caso de rotura traqueal tras una contusion en el
      cuello producto de un accidente de bicicleta que se trato de manera conservadora.

PMID- 27869434
TI  - [Childhood pemphigus vulgaris, a case report].
AB  - Pemphigus vulgaris is a chronic disease that is characterized by flaccid blisters
      and erosions, caused by immunoglobulin G autoantibodies against epidermal
      components. It is highly unusual in the pediatric population; it represents the
      1.4 - 2.9% of the total cases. We present a case of pemphigus vulgaris in a 12
      year old girl, which has implied a challenge both in its diagnosis and in its
      treatment.

PMID- 27869435
TI  - [Adolescent idiopathic scoliosis].
AB  - Adolescent idiopathic scoliosis is a 3D spinal deformity in frontal, sagittal and
      axial planes, with high relevance in the pediatric population especially in
      adolescents and females between 10 years of age and the end of growth spurt and
      skeletal maturity. The radiographic manifestation is a curve greater than 10
      degrees  measured by Cobb method associated with vertebral rotation. "Idiopathic"
      diagnosis has to be done after neuroanatomical anomalies of the posterior
      cerebral fosa and spinal canal have been ruled out. The physical finding of a
      thoracic or lumbar hump is the clinical manifestation of vertebral rotation seen
      in a forward bending test (Adam's Test). It is recommended that all curves with a
      magnitude greater than 20 degrees  have to be controlled and treated by a spinal
      surgeon being observation, bracing and surgery the different treatment options
      based on the extent, progression of deformity and basically the clinical
      condition of the patient.

PMID- 27869436
TI  - [Diagnosis and treatment guideline: asthma in children > 6 years. Update 2016.
      Executive summary].

PMID- 27869437
TI  - Immunology Update: Foreword.

PMID- 27869438
TI  - Immunology Update: Biologics.
AB  - Biologics are substances made from a living organism or its products. These
      include genes, proteins (eg, antibodies, receptors, enzymes, inhibitors),
      recombinant proteins, and fusion proteins. Biologics often are produced using
      recombinant DNA technology. For example, monoclonal antibodies are produced by
      inserting human genes into immortalized cell cultures, which then produce the
      gene product (ie, an antibody) in large quantity. Another approach is to fuse
      genetic material from nonhuman sources (eg, mice) with human genetic material.
      The fused gene is inserted into a tissue culture that produces the gene product
      (ie, a chimeric monoclonal antibody). Biologics are used to manage many
      conditions, including malignant and nonmalignant conditions. They are widely used
      in the treatment of human epidermal growth factor receptor 2 (ERBB2 [formerly
      HER2 or HER2/neu])-positive breast cancer. They also are used in the treatment of
      leukemias, lymphomas, and colorectal and lung cancer. Biologics improve outcomes
      in autoimmune disorders, such as rheumatoid arthritis, ankylosing spondylitis,
      psoriasis, inflammatory bowel disease, and multiple sclerosis. Other uses include
      erythropoietin for renal failure-associated anemia and the new proprotein
      convertase subtilisin/kexin type 9 (PCSK9) inhibitors for treatment of patients
      with persistently elevated low-density lipoprotein levels despite statin
      treatment who are at high risk of cardiovascular events.

PMID- 27869439
TI  - Immunology Update: Long-Term Care of Solid Organ Transplant Recipients.
AB  - Nearly 31,000 US patients received solid organ transplants in 2015 and the number
      is increasing. Care of transplant recipients includes management of a variety of
      common posttransplantation issues. Skin cancers are common because of
      immunosuppression and require skin examinations at intervals. Patients should be
      educated about the need to report new skin lesions. The rates of other cancers
      also are increased, including cancers of the head and neck, lung, esophagus,
      cervix, and urinary tract. Osteoporosis is common in transplant recipients;
      monitoring and early therapy are important. Patients should not smoke, and
      vaccinations should be current except for live-virus vaccines, which are
      contraindicated in patients with immunosuppression. Family physicians should be
      familiar with the posttransplantation immunosuppression drugs their patients are
      taking and know their adverse effects and drug interactions. For example,
      calcineurin inhibitors (eg, cyclosporine, tacrolimus) can impair renal function
      and increase rates of hypertension and myocardial ischemia. They also interact
      with statins, macrolide antibiotics, diltiazem, and other drugs. Interval
      laboratory testing is required to monitor the health of the transplanted organ
      (eg, renal function tests for kidney transplants, transaminases for liver
      transplants). Finally, clinicians should remain alert for development of
      opportunistic infection.

PMID- 27869440
TI  - Immunology Update: New Vaccines.
AB  - A new 9-valent human papillomavirus (HPV) vaccine is effective against more
      cancer-causing HPV types than previous vaccines. HPV vaccine series started with
      previous vaccines can be completed with the 9-valent vaccine. Two new influenza
      vaccines are available for adults 65 years and older: a high-dose vaccine and an
      enhanced adjuvant vaccine. These elicit stronger antibody responses than standard
      dose vaccines. Current guidelines specify no preference for the new versus
      standard-dose vaccines. Two new group B meningococcal vaccines are intended for
      use during outbreaks and for patients with asplenia, complement deficiencies,
      frequent occupational meningococcus exposure, or for patients who desire
      protection from type B meningococcus. These are not substitutes for the
      quadrivalent vaccine already in use. For pneumococcus, new recommendations state
      that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to
      patients 65 years and older, followed at least 1 year later by the polyvalent
      pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years
      with immunocompromise and not previously vaccinated against pneumococcus,
      administration of these two vaccines should be separated by at least 8 weeks.
      Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new
      cholera vaccine approved for use in the United States.

PMID- 27869442
TI  - [Two autopsy cases in which previous surgery facilitated the positive
      identification of decomposed bodies].
AB  - The positive identification of decomposed corpses is often difficult. We describe
      two autopsy cases in which medical materials, which had been implanted during
      previous surgical treatments, facilitated positive identification. The discovery
      of decomposed corpses is increasingly common in Japan, due to the increasing
      number of lonely deaths. Implanted medical materials and devices may be a useful
      tool for personal identification in the near future.

PMID- 27869441
TI  - Immunology Update: Primary Immunodeficiency Diseases.
AB  - There are 264 primary immunodeficiencies (PIDs), most of which are rare. They are
      caused by complement deficiencies, defects in phagocyte function, impaired T-cell
      function, and/or impaired B-cell function with antibody deficiencies. Most
      patients with PIDs will present, at varying ages, with frequent infections. These
      infections can be common respiratory tract infections such as otitis media or
      pneumonia, or they can be unusual bacterial, fungal, or parasitic infections.
      Neonatal screening for severe combined immunodeficiency syndrome, one of the most
      common and serious PIDs, is now performed in most US states, but many PIDs
      manifest and are detected after birth. Clinicians should be alert for PIDs when
      patients have unusual or frequent infection and perform a diagnostic evaluation.
      After ruling out HIV and hepatitis C infection, the next step is to obtain a
      complete blood count, immunodeficiency panel, and immunoglobulin and complement
      levels. If results are abnormal, or if a PID is suspected clinically but the
      diagnosis is not clear, prompt referral to an appropriate subspecialist is
      indicated. Some PIDs can be managed with stem cell transplantation, and
      transplantation before the first serious infection is associated with better
      outcomes. In addition, antimicrobial prophylaxis is indicated for many PIDs
      patients to prevent opportunistic infections.

PMID- 27869443
TI  - [Post mortem investigation of alveolar air in forensic practice].
AB  - Exhaled air from biological materials is used for the purpose of toxicologico
      chemical analysis particularly in detecting of alcohol influence in traffic or
      within a working process. Similarly, still a more and more actual requirement
      seems to be a necessity to analyse alveolar air from necroptic material. This
      necessity is emphasised not only by the fact, that inhalant intoxications in the
      form of poisoning represent their substantial part, but also a demand to evidence
      exactly a noxious agent both specifically and also in at least two materials. And
      particularly this is sometimes a subject to search for evidence in alveolar air.
      The authors present their authors certificates for Isolation of alveolar air from
      autopsy material, issued by the Office for Patents and Inventions in Prague,
      verified in practice, both by destruction of lung tissue, both the evacuation of
      alveolar air into a defined volume, hermetically closed space that is used for
      the toxicological analysis of gaseous and volatile xenobiotics. They propose
      experimentally verified procedures and conditions obtained by time-consuming
      examination. To isolation procedures were subjected an adequate number of lung
      lobes from lungs removed in 201 autopsy cases. The authors practically tested the
      presupposed amount of alveolar air in individuals according to gender and age.
      Gradually they have validated various prototypes and optimization methods and
      their application in solving particular inhaled lethal intoxications and deaths
      in the irrespirable environment.

PMID- 27869444
TI  - [BRCA1 and BRCA2 - pathologists starting kit].
AB  - Dysfunction of tumor suppressor genes BRCA1 and BRCA2 is involved in the
      pathogenesis of malignant tumors, especially breast and ovarian carcinoma.
      BRCA1/2 genes may be inactivated by germinal and somatic mutations or epigenetic
      changes. Germinal mutations are responsible for the hereditary breast and ovarian
      carcinoma syndrome. Defects of BRCA1/2 genes lead to the failure of homologous
      recombination, the basic mechanism for DNA double strand break repair. The
      resultant genomic instability is associated with a high risk of malignant
      transformation of the cell, but it also results in a higher sensitivity of tumors
      to platinum-based chemotherapeutic compounds which damage DNA structure directly.
      Inhibitors of poly(ADP-ribose) polymerase (PARP) are the next generation of
      antitumor agents aimed on the suppression of DNA single strand break repair. In
      homologous recombination deficient tumors, PARP inhibitors lead to accumulation
      of DNA damage and death of neoplastic cells through the mechanism of synthetic
      lethality. Platinum-based agents and PARP inhibitors are effective not only
      against tumors with germinal and somatic BRCA1/2 mutations but also against
      sporadic carcinomas with epigenetic BRCA1/2 inactivation or with defects of other
      independent genes involved in the control of homologous recombination. This
      phenomenon is represented by the term "BRCAness". Mutational analysis is used for
      the assessment of BRCA1/2 status, but it is complicated by the prominent length
      of BRCA1/2 genes and a wide spectrum of possible genetic alterations. Therefore,
      next generation sequencing seems to represent an optimal approach for BRCA1/2
      evaluation nowadays. Development of reliable diagnostic tests for BRCAness in
      sporadic tumors and efforts to reverse platinum and PARP inhibitors resistance
      represent the key objectives of the forthcoming research.

PMID- 27869445
TI  - [Breast cancer in BRCA1/2 mutation carriers].
AB  - Inherited mutations in BRCA1 and BRCA2 genes represent the most important cause
      of hereditary breast cancer. This highly penetrating familial cancer syndrome,
      including also the onset of ovarian cancer and other malignancies at relatively
      low age, represents a substantial medical problem. The affected families should
      be managed actively. When compared to spontaneous tumors, the breast carcinomas
      in BRCA1 mutation carriers exhibit a relatively different, despite non-specific,
      phenotype (often triple negative, medullary features) arousing suspicion of
      hereditary background. In the contrary, the distribution of phenotypes of breast
      carcinomas in BRCA2 carriers is similar to distribution in the non-affected
      population. The lymphocytic lobulitis is observed significantly more often in non
      cancerous breast tissue of BRCA1/2 mutation carriers, but again, this feature is
      not specific.

PMID- 27869446
TI  - [Oncopathological aspects of BRCA1 and BRCA2 genes inactivation in tumors of
      ovary, fallopian tube and pelvic peritoneum].
AB  - Ovarian carcinoma represents a heterogeneous group of malignant epithelial tumors
      which could be divided into two fundamental groups: Type I (endometrioid
      carcinoma, clear cell carcinoma, low grade serous carcinoma, mucinous carcinoma
      and more rare seromucinous carcinoma and malignant Brenner tumor) and type II
      (high grade serous carcinoma - HGSC). HGSC is the most frequent ovarian carcinoma
      which may be etiologically linked to inactivation of tumor suppressor genes
      BRCA1/2 and TP53 and differs from type I carcinomas by higher aggressiveness,
      tendency to peritoneal spread and worse prognosis. A precursor lesion of HGSC was
      described as a serous tubal intraepithelial carcinoma (STIC) which is usually
      localized in fimbria of the fallopian tube from where tumor cells are capable to
      implant on ovary and pelvic peritoneum. Therefore, HGSC may present itself not
      only as a tuboovarian tumor but also as a primary peritoneal carcinoma. HGSC
      constitutes a dominant group within hereditary ovarian carcinomas as a
      manifestation of hereditary breast and ovarian cancer or site-specific ovarian
      cancer syndromes which are associated with germinal mutations of BRCA1/2 genes.
      BRCA1 deficient HGSC show characteristic histological appearance which
      encompasses SET features (Solid-pseudoEndometrioid-Transitional), significant
      nuclear atypia and mitotic activity, geographic necrosis, marked lymphocytic
      infiltration and abnormalities in TP53 expression. Use of immunohistochemistry as
      a screening method for BRCA1/2 inactivation is questionable at this time.
      Bilateral adnexectomy is considered to be a standard prophylactic treatment of
      women affected by germinal BRCA1/2 mutation. In that case, fallopian tubes should
      be submitted completely for the histological evaluation according to the SEE-FIM
      protocol (Sectioning and Extensively Examining the FIMbria) due to the risk of
      STIC or occult HGSC. Tumors with BRCA1/2 inactivation show a better therapeutic
      response to platinum-based chemotherapeutic compounds and a more favorable
      prognosis. Inhibitors of poly(ADP-ribose) polymerase (PARP) are the next
      generation of antitumor agents comprising olaparib which is implemented in
      clinical practice currently. Germinal or somatic inactivation of BRCA1/2 serves
      as a predictor for targeted oncologic therapy by PARP inhibitors, therefore
      evaluation of these genes in ovarian carcinoma patients will be carried out by
      departments of pathology and clinical genetics. Next generation sequencing seems
      to be an ideal method for the reduction of the time factor and optimization of
      BRCA1/2 analysis. Unfortunately, a routine test for the evaluation of homologous
      recombination functionality and detection of "BRCAness" in sporadic tumors is
      still not available.

PMID- 27869448
TI  - Clear cell sarcoma of vulva. A case report.
AB  - We report the case of a 67-year-old female with clear cell sarcoma (CCS) of the
      vulva. Grossly, the tumor was a partly exophytical vulvar mass, measuring 20 x 15
      cm. At the time of presentation, the patient showed metastases to the lung,
      inguinal and pelvic lymph nodes. Histologically, the tumor consisted of oval or
      spindle cells with only mild nuclear pleomorphism and rare mitoses (up to 2/10
      HPF). The cytoplasm was pale eosinophilic or clear. The tumor cells were arranged
      in confluent sheets. There were large areas of necrosis and surface ulceration.
      Immunohistochemically, the tumor cells showed expression of S-100 protein and
      focal melan A and HMB45 expression. Fluorescent in situ hybridization analysis
      revealed rearrangement of the EWSR1 gene. To the best of our knowledge, this is
      the first report of CCS arising in the vulva.

PMID- 27869447
TI  - [Testing of mutations in BRCA1 and BRCA2 genes in tumor tissues - possibilities
      and limitations].
AB  - Development of targeted cancer therapy is accompanied by a search for markers
      allowing prediction of response to the particular treatment. Recently, the
      interest is focused, among other neoplasms, also on the therapy of ovarian cancer
      using new inhibitors of poly (ADP-ribose) polymerase (PARP) proteins, nuclear
      enzymes involved in the repair of single-stranded DNA breaks. The greatest
      benefit from the administration of PARP inhibitors have patients with a
      deleterious or potentially deleterious germ-line or somatic mutation of BRCA1 or
      BRCA2, two genes responsible for repair of double stranded DNA breaks. There has
      been described a wide spectrum of mutations of BRCA 1/2, from point substitutions
      to large deletions, including sometimes even several exons of the gene.Unlike the
      testing of germ-line mutations provided for many years by the medical
      geneticists, somatic mutations in the tumor tissue have not been routinely tested
      so far. Detection of BRCA1/2 mutations in the tumor is significantly different
      from testing of germ-line mutations. In comparison with the analysis of DNA
      isolated from blood samples, testing of DNA isolated from the FFPE tissue
      encounters challenges based on heterogeneous representation of tumor cells in the
      tissue samples, on the presence of multiple neoplastic clones and on the
      infiltration of tissue by the non-neoplastic elements, as well as difficulties
      caused by variable proportion of apoptotic and necrotic cells deteriorating the
      overall quality of isolated DNA.Regarding the testing methods, NGS appears to be
      the optimal choice because of its complexity, speed of implementation into
      routine diagnostics as well as sensitivity for detection of a BRCA 1/2 mutations.
      When introduced into everyday laboratory practice, the functioning quality
      control system is of utmost importance. Provided there is a high probability of
      detection of the so far unreported variations in BRCA 1/2 genes, an introduction
      of a shared database of somatic variants diagnosed in the Czech Republic would be
      of enormous benefit.

PMID- 27869449
TI  - [Diffuse tenosynovial giant cell tumor of the cervical spine destroying vertebra
      C6 - a case report].
AB  - Presented is a case of 59-year-old woman with longstanding neck pain who has been
      promptly operated for spinal cord compression. Imaging studies disclosed ill
      defined cervical paravertebral soft tissue mass at the level of vertebra C5/6
      abutting left-sided intervertebral joint and destroying neighboring both
      vertebral arch and processus spinosus. Submitted specimen was interpreted as a
      possible metastatic skeletal process by clinicians and referring pathologist
      favored diagnosis of giant cell tumor/osteoclastoma of the bone. Microscopic
      features were consistent with giant cell lesion where uniform mononuclear mosaic
      stromal component dominated the unevenly distributed loose clusters of osteoclast
      like giant cells frequently imparting appearance of peculiar pseudoalveolar
      spaces. Additionally, alternating geographic xanthomatous and densely hyalinized/
      osteoid-like zones with speckled, coarsely granular haemosiderin pigment
      completed the variegated structural composition. The tumor infiltrated adjacent
      striated muscles; either original bone structures and/or extracellular matrix
      deposits were not identified. Immunohistochemical stains with p63, SATB2, desmin,
      EMA, clusterin and S100protein turned out to be completely negative. FISH
      analysis revealed no rearrangement of CSF1 gene. The diagnosis of the diffuse
      tenosynovial giant cell tumor was rendered.

PMID- 27869450
TI  - Basal cell carcinoma of the skin with mixed histomorphology: a comparative study.
AB  - Basal cell carcinoma (BCC) of the skin exhibits a very heterogeneous
      histomorphology, on the basis of which it is classified into several subtypes and
      variants. In many cases, however, a definite categorization remains difficult,
      because BCC may consist of more than one histopathological subtype. There are
      limited data exploring the characteristics of these mixed BCCs, since they have
      not been specifically analysed. The aim of this study was to estimate the
      prevalence of BCCs with mixed histomorphology observed in a set of primary BCCs
      and to compare their clinicopathological features with a single type BCC
      subgroup. A total of 911 histologically proven primary BCCs from 697 patients
      were investigated. Prevalence of single and mixed type BCCs was 64.9 % and 35.1
      %, respectively. In mixed type BCC subgroup, a very heterogeneous histomorphology
      was found comprising a mixture of two to four different subtypes in various
      proportions. The most frequent combinations included nodular-infiltrative,
      superficial-nodular, nodular-trichoepithelial and nodular-micronodular subtype.
      Comparative analysis of the two given subgroups showed that mixed type BCCs were
      significantly more frequently localized on the extrafacial regions of the head
      (30.0 % vs. 20.0 %, p = 0.02) and less often on the face (37.2 % vs. 45.2 %, p =
      0.03). There were not convincing differences in the occurrence of single vs mixed
      type BCCs in other parts of the body. Histologically, mixed type BCCs exhibited
      an aggressive-growth pattern more frequently (64.6 % vs. 13.0 %, p < 0.0001).
      Positive surgical margins were significantly more common in mixed type BCC
      subgroup (17.8 % vs. 12.6 %, p = 0.02). Cutaneous BCCs with mixed histomorphology
      represented about one third of the cases. It is a common finding in routine
      pathological practice, probably suggestive of evolution and phenotypic
      transformation of the cancer. Since mixed type BCCs are frequently composed of
      aggressive histological subtypes, regardless the personal habits in description
      or terminology among pathologists, the presence of aggressive-growth component in
      tumor tissue should always be mentioned in final biopsy report.

PMID- 27869452
TI  - Dyadic effects of attachment on mental health: Couples in a postdisaster context.
AB  - Research on mental health following disasters has led to the identification of
      many individual protective and risk factors for postdisaster mental health.
      However, there is little understanding of the exact influence that disasters have
      on the functioning of intimate relationships. Especially relevant are attachment
      styles, which are likely to play an important role in the provision and
      perception of social support between partners, and subsequent mental health
      outcomes. Heterosexual couples (N = 127) affected by the 2009 Victorian "Black
      Saturday" Bushfires in southeastern Australia were surveyed for disaster
      experiences, posttraumatic stress disorder (PTSD) symptoms, depression, and
      attachment style between May 2012 and January 2013, approximately 3 years after
      the disaster. Using actor-partner interdependence models (APIM), we examined both
      intrapersonal and interpersonal associations of attachment anxiety and avoidance
      with depression and PTSD, in combination with shared disaster exposure. Male
      partners' attachment avoidance was associated with depression and PTSD in both
      partners. By contrast, a female partner's attachment avoidance was associated
      with greater depression and PTSD in herself, but fewer PTSD symptoms in a male
      partner. Amid the chronic stressors of a postdisaster setting, the attachment
      avoidance of the male partner may play a particularly negative role, with his
      tendency toward isolation and denial becoming especially maladaptive for the
      couple as a whole. The female partner's attachment avoidance is likewise an
      important factor, but its associations with negative social support and
      relationship breakup must be clarified to understand its impact on partnership
      functioning. (PsycINFO Database Record

PMID- 27869451
TI  - Internet-delivered, family-based treatment for early-onset OCD: A pilot
      randomized trial.
AB  - OBJECTIVE: Despite advances in supported treatments for early onset obsessive
      compulsive disorder (OCD), progress has been constrained by regionally limited
      expertise in pediatric OCD. Videoteleconferencing (VTC) methods have proved
      useful for extending the reach of services for older individuals, but no
      randomized clinical trials (RCTs) have evaluated VTC for treating early onset
      OCD. METHOD: RCT comparing VTC-delivered family based cognitive-behavioral
      therapy (FB-CBT) versus clinic-based FB-CBT in the treatment of children ages 4-8
      with OCD (N = 22). Pretreatment, posttreatment, and 6-month follow-up assessments
      included mother-/therapist-reports and independent evaluations masked to
      treatment condition. Primary analyses focused on treatment retention, engagement
      and satisfaction. Hierarchical linear modeling preliminarily evaluated the
      effects of time, treatment condition, and their interactions. "Excellent
      response" was defined as a 1 or 2 on the Clinical Global Impressions-Improvement
      Scale. RESULTS: Treatment retention, engagement, alliance and satisfaction were
      high across conditions. Symptom trajectories and family accommodation across both
      conditions showed outcomes improving from baseline to posttreatment, and
      continuing through follow-up. At posttreatment, 72.7% of Internet cases and 60%
      of Clinic cases showed "excellent response," and at follow-up 80% of Internet
      cases and 66.7% of Clinic cases showed "excellent response." Significant
      condition differences were not found across outcomes. CONCLUSIONS: VTC methods
      may offer solutions to overcoming traditional barriers to care for early onset
      OCD by extending the reach of real-time expert services regardless of children's
      geographic proximity to quality care. (PsycINFO Database Record

PMID- 27869453
TI  - In search of a new identity: An institutional consultation at a sub-acute
      inpatient unit in a general hospital.
AB  - INTRODUCTION: Hospitals are constantly morphing under the pressure of ever
      evolving health care technologies, procedures, and reimbursement practices. In
      turn, healthy institutional identities and personnel allegiance contribute to
      counterbalance the potentially destabilizing effects of those changes. An
      institutional consultation was requested at a general hospital recently created
      sub-acute unit (SAU) due to malaise and dissatisfaction in the nursing staff.
      METHOD: The consultation included a total of 3 group meetings with the SAU
      nursing staff as well as observation of procedures and milieu in this and
      adjacent units. In the course of this process, a structure of demeaning
      narratives about the unit and the nursing personnel's own role in the context of
      changes within the hospital was detected, destabilized, and transformed, and the
      kernel of a new identity for the unit was developed, using a shift in a routine
      evaluation procedure for patient's progress as a fulcrum for generating change.
      RESULTS: Follow-up evaluation indicated a qualitative improvement in the unit
      milieu and nurses' job satisfaction, resonating with an enhancement in the
      staff's identification with the unit's reformulated mission as part of a
      constructive continuum of care. This improvement was also acknowledged and
      rewarded by hospital administration. DISCUSSION: While maintaining a stance of
      positive connotation, assumptions of good intent, and a systemic view of the
      organization, demeaning collective narratives can be transformed through timely
      interventions that restitute pride and meaningfulness to the personnel and
      improve the unit's quality of care. (PsycINFO Database Record

PMID- 27869454
TI  - Meta-analyses of the relationship between conformity to masculine norms and
      mental health-related outcomes.
AB  - Despite theoretical postulations that individuals' conformity to masculine norms
      is differentially related to mental health-related outcomes depending on a
      variety of contexts, there has not been any systematic synthesis of the empirical
      research on this topic. Therefore, the authors of this study conducted meta
      analyses of the relationships between conformity to masculine norms (as measured
      by the Conformity to Masculine Norms Inventory-94 and other versions of this
      scale) and mental health-related outcomes using 78 samples and 19,453
      participants. Conformity to masculine norms was modestly and unfavorably
      associated with mental health as well as moderately and unfavorably related to
      psychological help seeking. The authors also identified several moderation
      effects. Conformity to masculine norms was more strongly correlated with negative
      social functioning than with psychological indicators of negative mental health.
      Conformity to the specific masculine norms of self-reliance, power over women,
      and playboy were unfavorably, robustly, and consistently related to mental health
      related outcomes, whereas conformity to the masculine norm of primacy of work was
      not significantly related to any mental health-related outcome. These findings
      highlight the need for researchers to disaggregate the generic construct of
      conformity to masculine norms and to focus instead on specific dimensions of
      masculine norms and their differential associations with other outcomes.
      (PsycINFO Database Record

PMID- 27869455
TI  - An interference model of visual working memory.
AB  - The article introduces an interference model of working memory for information in
      a continuous similarity space, such as the features of visual objects. The model
      incorporates the following assumptions: (a) Probability of retrieval is
      determined by the relative activation of each retrieval candidate at the time of
      retrieval; (b) activation comes from 3 sources in memory: cue-based retrieval
      using context cues, context-independent memory for relevant contents, and noise;
      (c) 1 memory object and its context can be held in the focus of attention, where
      it is represented with higher precision, and partly shielded against
      interference. The model was fit to data from 4 continuous-reproduction
      experiments testing working memory for colors or orientations. The experiments
      involved variations of set size, kind of context cues, precueing, and retro
      cueing of the to-be-tested item. The interference model fit the data better than
      2 competing models, the Slot-Averaging model and the Variable-Precision resource
      model. The interference model also fared well in comparison to several new models
      incorporating alternative theoretical assumptions. The experiments confirm 3
      novel predictions of the interference model: (a) Nontargets intrude in recall to
      the extent that they are close to the target in context space; (b) similarity
      between target and nontarget features improves recall, and (c) precueing-but not
      retro-cueing-the target substantially reduces the set-size effect. The success of
      the interference model shows that working memory for continuous visual
      information works according to the same principles as working memory for more
      discrete (e.g., verbal) contents. Data and model codes are available at
      https://osf.io/wgqd5/. (PsycINFO Database Record

PMID- 27869456
TI  - Evaluation of relational reasoning by a transitive inference task in attention
      deficit/hyperactivity disorder.
AB  - OBJECTIVE: Here we explored whether children with ADHD have a deficit in
      relational reasoning, a skill subtending the acquisition of many cognitive
      abilities and social rules. METHOD: We analyzed the performance of a group of
      children with ADHD during a transitive inference task, a task requiring first to
      learn the reciprocal relationship between adjacent items of a rank ordered series
      (e.g., A>B; B>C; C>D; D>E; E>F), and second, to deduct the relationship between
      novel pairs of items never matched during the learning (e.g., B>D; C>E). RESULTS:
      As a main result, we observed that children with ADHD were impaired in performing
      inferential reasoning problems. The deficit in relational reasoning was found to
      be related to the difficulty in managing a unified representation of ordered
      items. CONCLUSION: The present finding documented a novel deficit in ADHD,
      contributing to improving the understanding of the disorder. (PsycINFO Database
      Record

PMID- 27869457
TI  - Autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN)
      associated with progressive cognitive and behavioral deterioration.
AB  - OBJECTIVE: Autosomal dominant cerebellar ataxia with deafness and narcolepsy
      (ADCA-DN) is an emerging syndrome caused by mutations in the C-terminus end of
      the TS domain of the DNMT1 gene. ADCA-DN is also associated with sensorimotor
      polyneuropathy, extrapyramidal, and dysautonomic signs, as well as dementia.
      Little has been reported about the progressive cognitive impairment associated
      with ADCA-DN. Our objective is to provide a detailed characterization of the
      cognitive profile of ADCA-DN. METHOD: Three members of a kindred with ADCA-DN
      underwent comprehensive neuropsychological testing and neuroimaging. RESULTS: At
      baseline, 2 individuals demonstrated cognitive profiles with executive
      difficulties in some areas consistent with frontal-system dysfunction
      behaviorally and on standardized testing. The third individual was further in the
      disease course and exhibited more globally impaired cognition consistent with a
      diagnosis of dementia. CONCLUSIONS: This family demonstrated progressive
      neurodegeneration beginning with isolated areas of executive dysfunction and
      leading to globally impaired cognition and dementia. Cognitive decline occurred
      in parallel with neurological deterioration. The cognitive profile is similar to
      case reports of other individuals with an allelic neurological phenotype,
      Hereditary Sensory Autonomic Neuropathy 1E, also caused by DNMT1 mutations.
      (PsycINFO Database Record

PMID- 27869458
TI  - Smith and Lilienfeld's meta-analysis of the response modulation hypothesis:
      Important theoretical and quantitative clarifications.
AB  - In the first meta-analytic review of the response modulation hypothesis (RMH), an
      attention-based model for understanding the etiology of psychopathy, Smith and
      Lilienfeld (2015) report that the average effect size for response modulation
      deficits in psychopathic individuals fell in the small to medium range (r = .20;
      p < .001, d = .41). Moreover, support for the RMH extended to both psychopathy
      dimensions, applied across diverse assessments and settings, and spanned child,
      adult, female, and male samples. The analysis also revealed good empirical
      support for a central tenet of the RMH, namely that response modulation deficits
      are not limited to the processing of threat or other emotion stimuli.
      Unfortunately, the Smith and Lilienfeld meta-analysis contains several
      theoretical and quantitative problems, including failing to distinguish
      adequately between the tasks used to evaluate RMH predictions and the theory
      itself, confusion regarding the evolution of the RMH and its impact on effect
      sizes, misinterpretations of RMH predictions and evidence regarding dominant
      response sets, passive avoidance, and primary task performance, and biased
      statements promoting the low fear model over the RMH. In this response, we
      endeavor to reduce misunderstanding by addressing the most salient issues, with
      the hope that increasing clarity will sharpen the focus of future research and
      result in more valid assessments of the RMH. (PsycINFO Database Record

PMID- 27869459
TI  - The perils of unitary models of the etiology of mental disorders-The response
      modulation hypothesis of psychopathy as a case example: Rejoinder to Newman and
      Baskin-Sommers (2016).
AB  - We respond to Newman and Baskin-Sommers's (2016) criticisms of our meta-analytic
      and narrative synthesis of the response modulation hypothesis (RMH) of
      psychopathy (Smith & Lilienfeld, 2015). We concur with Newman and Baskin-Sommers
      that our results offer modest support for the RMH and that several of our
      arguments apply with equal force to rival etiological models of psychopathy.
      Nevertheless, we contend that Newman and Baskin-Sommers' criticisms of our
      findings and conclusions are unconvincing, and that the research support for the
      RMH is considerably more mixed than implied by Newman and Baskin-Sommers. We
      address a number of conceptual and methodological concerns regarding the RMH
      literature, especially (a) the ambiguous operationalization of a dominant
      response set, (b) selective and inconsistent interpretation of findings, (c) the
      failure of successive modifications in the RMH to bolster the model's predictive
      power, (d) the hazards of ex juvantibus logic (reasoning backward from what
      works), (e) reliance on a positive test strategy in theory testing, and (f) the
      questionable assumption that psychopathy is a monolithic entity, rendering it
      unlikely that the RMH provides a comprehensive causal account of psychopathy. We
      conclude with a discussion of broader lessons for the psychopathy field imparted
      by the RMH debate, with particular emphasis on the problematic track record of
      models of specific etiology in the field of psychopathology at large. (PsycINFO
      Database Record

PMID- 27869460
TI  - "Neural responses to gains and losses in children of suicide attempters":
      Correction to Tsypes et al. (2016).
AB  - Reports an error in "Neural Responses to Gains and Losses in Children of Suicide
      Attempters" by Aliona Tsypes, Max Owens, Greg Hajcak and Brandon E. Gibb (Journal
      of Abnormal Psychology, Advanced Online Publication, Nov 3, 2016, np). In the
      article, Figure 1 had incorrect axis labels. There was also an error in the
      abstract, which did not state that DeltaFN was calculated as FN to losses minus
      FN to gains. All versions of this article have been corrected. (The following
      abstract of the original article appeared in record 2016-53087-001.) Suicidal
      behavior aggregates within families, yet the specific mechanisms of suicide-risk
      transmission are poorly understood. Despite some evidence that abnormal patterns
      of reward responsiveness might constitute one such potential mechanism, empirical
      evidence is lacking. The goal of this study was to examine neural responses to
      gains and losses in children of suicide attempters with no personal history of
      suicide attempt (SA) themselves. To objectively assess these neural responses, we
      used feedback negativity (FN), a psychophysiological marker of responsiveness to
      reward and loss. Participants were 66 parents and their 7-11-year-old children
      (22 with parental history of SA and 44 demographically and clinically matched
      children of parents with no SA history). Diagnostic interviews were used to
      gather information about psychiatric diagnoses, symptoms, and histories of
      suicidal thoughts and behaviors. Children also completed a guessing task, during
      which continuous electroencephalography (EEG) was recorded. The FN was scored as
      the mean amplitude, 275-375 ms, following gain or loss feedback at frontocentral
      sites (Fz and FCz). Children of suicide attempters exhibited significantly more
      negative DeltaFN (i.e., FN to losses minus FN to gains) than children of parents
      with no SA history. We found that this difference in DeltaFN was due specifically
      to children of parents with a history of SA exhibiting a stronger response to
      loss, and no group differences were observed for responses to gains. The results
      suggest that an increased neural response to loss might represent one of the
      potential pathways of the familial transmission of suicide risk. (PsycINFO
      Database Record

PMID- 27869462
TI  - Development and validation of a brief trauma screening measure for children: The
      Child Trauma Screen.
AB  - OBJECTIVE: Childhood exposure to trauma, including violence and abuse, is a major
      public health concern that has resulted in increased efforts to promote trauma
      informed child-serving systems. Trauma screening is an important component of
      such trauma-informed systems, yet widespread use of trauma screening is rare in
      part due to the lack of brief, validated trauma screening measures for children.
      We describe development and validation of the Child Trauma Screen (CTS), a 10
      item screening measure of trauma exposure and posttraumatic stress disorder
      (PTSD) symptoms for children consistent with the DSM-5 definition of PTSD.
      METHOD: Study 1 describes measure development incorporating analysis to derive
      items based on existing measures from 1,065 children and caregivers together with
      stakeholder input to finalize item selection. Study 2 describes validation of the
      CTS with a clinical sample of 74 children and their caregivers. RESULTS: Results
      support the CTS as an empirically derived, reliable measure to screen children
      for trauma exposure and PTSD symptoms with strong convergent, divergent, and
      criterion validity. CONCLUSION: The CTS is a promising measure for rapidly and
      reliably screening children for trauma exposure and PTSD symptoms. Future
      research is needed to confirm validation and to examine feasibility and utility
      of its use across various child-serving systems. (PsycINFO Database Record

PMID- 27869461
TI  - Race differences in depression vulnerability following Hurricane Katrina.
AB  - OBJECTIVE: This study investigated whether racial disparities in depression were
      present after Hurricane Katrina. METHOD: Data were gathered from 932 New Orleans
      residents who were present when Hurricane Katrina struck, and who returned to New
      Orleans the following year. Multiple logistic regression models evaluated racial
      differences in screening positive for depression (a score >=16 on the Center for
      Epidemiologic Studies Depression Scale), and explored whether differential
      vulnerability (prehurricane physical and mental health functioning and education
      level), differential exposure to hurricane-related stressors, and loss of social
      support moderated and/or reduced the association of race with depression.
      RESULTS: A univariate logistic regression analysis showed the odds for screening
      positive for depression were 86% higher for African Americans than for Caucasians
      (odds ratio [OR] = 1.86 [1.28-2.71], p = .0012). However, after controlling
      simultaneously for sociodemographic characteristics, preexisting vulnerabilities,
      social support, and trauma-specific factors, race was no longer a significant
      correlate for screening positive for depression (OR = 1.54 [0.95-2.48], p =
      .0771). CONCLUSIONS: The racial disparity in postdisaster depression seems to be
      confounded by sociodemographic characteristics, preexisting vulnerabilities,
      social support, and trauma-specific factors. Nonetheless, even after adjusting
      for these factors, there was a nonsignificant trend effect for race, which could
      suggest race played an important role in depression outcomes following Hurricane
      Katrina. Future studies should examine these associations prospectively, using
      stronger assessments for depression, and incorporate measures for discrimination
      and segregation, to further understand possible racial disparities in depression
      after Hurricane Katrina. (PsycINFO Database Record

PMID- 27869463
TI  - Posttraumatic stress disorder in Latina women: Examining the efficacy of the
      Moms' Empowerment Program.
AB  - OBJECTIVE: Intimate partner violence (IPV) is a serious public health problem,
      affecting every 1 in 4 women in their lifetime. Latinas have been found to
      experience IPV at rates equal to or even higher than rates in the general
      population. The consequences of experiencing such violence can be severe, and
      result in increased risk for developing both physical and mental health problems,
      notably, posttraumatic stress disorder (PTSD). Although treatments for PTSD in
      IPV-exposed women have been developed and evaluated, this is the first study to
      test the efficacy of a program tailored specifically to meet the needs of Latinas
      who experience IPV. METHOD: This study examines the efficacy of a Spanish
      language adaptation of the Moms' Empowerment Program, a 10-week group treatment
      program for IPV-exposed women. A total of 93 low-income, mostly immigrant Latinas
      were included in this community trial. All women were Spanish-speaking, and
      information about violence exposure and PTSD symptoms were collected immediately
      before and after the implementation of the intervention. RESULTS: Findings show
      that women who participated in the intervention had a significantly greater
      reduction in PTSD symptoms than women in the wait-list comparison group. Specific
      reductions by symptom domains were also analyzed. CONCLUSIONS: This adaptation of
      a program designed to reduce problems associated with experiencing IPV addressed
      several mental health treatment needs for Latinas, particularly the need for
      services in Spanish. These findings demonstrate that it is possible to tailor
      current treatment programs for IPV in ways that are both effective and culturally
      sensitive. (PsycINFO Database Record

PMID- 27869464
TI  - Customized computer-based administration of the PCL-5 for the efficient
      assessment of PTSD: A proof-of-principle study.
AB  - OBJECTIVE: To investigate the potential of customized computer-based testing
      procedures to reduce the mean test length of the Posttraumatic Stress Checklist
      for DSM-5 (PCL-5). METHOD: A retrospective analysis was conducted using responses
      from 942 adults who had completed the full-length (20-item) PCL-5 in the
      aftermath of Hurricane Sandy. The abilities of 2 testing procedures, curtailment
      and stochastic curtailment, to lessen the instrument's mean test length while
      maintaining the same result as the full-length PCL-5 ("positive" or "negative")
      were evaluated in a post hoc simulation. Curtailment and stochastic curtailment
      track a respondent's answers as she takes the instrument and stop the test if
      future items are unable or unlikely to change the result. The performance of each
      procedure was recorded under 2 scoring methods: a total-score-based method and a
      cluster-based method. Each procedure's sensitivity, specificity, and overall
      agreement with the full-length PCL-5 were computed. RESULTS: Curtailment reduced
      the mean test length by 40% under the total-score-based method, and by more than
      70% under the cluster-based method, while exhibiting 100% sensitivity,
      specificity, and overall agreement with the full-length PCL-5. Stochastic
      curtailment reduced the mean test length by up to 88% under the total-score-based
      method, and up to 84% under the cluster-based method, while always exhibiting at
      least 92% sensitivity and 99.8% overall agreement, as well as 100% specificity,
      for the full-length PCL-5. CONCLUSIONS: Curtailment and stochastic curtailment
      have potential to enhance the efficiency of the PCL-5 when this assessment is
      administered by computer. The 2 procedures should be evaluated in future
      prospective studies. (PsycINFO Database Record

PMID- 27869466
TI  - Safety first: Instrumentality for reaching safety determines attention allocation
      under threat.
AB  - Theories of attention to emotional information suggest that attentional processes
      prioritize threatening information. In this article, we suggest that attention
      will prioritize the events that are most instrumental to a goal in any given
      context, which in threatening situations is typically reaching safety. To test
      our hypotheses, we used an attentional cueing paradigm that contained cues
      signaling imminent threat (i.e., aversive noises) as well as cues that allowed
      participants to avoid threat (instrumental safety signals). Correct reactions to
      instrumental safety signals seemingly allowed participants to lower the
      presentation rate of the threat. Experiment 1 demonstrates that attention
      prioritizes instrumental safety signals over threat signals. Experiment 2
      replicates this finding and additionally compares instrumental safety signals to
      other action-relevant signals controlling for action relevance as cause of the
      effects. Experiment 3 demonstrates that when actions toward threat signals permit
      to avoid threat, attention prioritizes threat signals. Taken together, these
      results support the view that instrumentality for reaching safety determines the
      allocation of attention under threat. (PsycINFO Database Record

PMID- 27869465
TI  - Association of peritraumatic dissociation with symptoms of depression and
      posttraumatic stress disorder.
AB  - AIM: In this study, we evaluated whether peritraumatic dissociation (PD) was
      associated with symptoms of depression and posttraumatic stress disorder (PTSD),
      and whether this association was modified by trauma prior to police work. METHOD:
      Symptoms of depression, PTSD, peritraumatic dissociative experience (PDE), and
      trauma prior to police work were measured using the Center for Epidemiologic
      Studies Depression scale, PTSD Checklist-Civilian, PDE questionnaire, and the
      Brief Trauma questionnaire, respectively, in 328 police officers. Separate
      regression models were used to assess if either symptoms of depression or PTSD
      were associated with PD stratified by prior trauma. Means were adjusted for race,
      number of drinks per week, and smoking. RESULTS: PD was associated with symptoms
      of PTSD and depression (beta = 0.65, p < .001 and beta = 0.27, p < .001,
      respectively). PD was positively associated with symptoms of PTSD regardless of
      prior trauma (beta = 0.61, p < .001(without prior trauma), 0.75, p < .001 (with
      prior trauma). In contrast to PTSD, depression symptoms were significantly
      associated with PD scores in individuals with prior trauma (beta = 0.47, p <
      .001), but not in individuals without prior trauma (beta = 0.13, p = .165).
      LIMITATIONS: This is a cross-sectional study. Outcomes were obtained via self
      report and were not clinically diagnosed. Aspects of both the trauma event as
      well as the symptoms and severity of PD may have introduced recall bias.
      CONCLUSION: These results add to the literature indicating that PD plays a role
      in symptoms of PTSD and depression and how prior trauma may modify this
      relationship. (PsycINFO Database Record

PMID- 27869467
TI  - How the social ecology and social situation shape individuals' affect valence and
      arousal.
AB  - Many theories highlight the role social contexts play in shaping affective
      experience. However, little is known about how individuals' social environments
      influence core affect on short time-scales (e.g., hours). Using experience
      sampling data from the iSAHIB, wherein 150 adults aged 18 to 89 years reported on
      64,213 social interactions (average 6.92 per day, SD = 2.85) across 9 weeks of
      daily life, we examined how 4 features of individuals' social ecology (between
      person differences) and immediate social situations (within-person changes) were
      associated with core affect-valence and arousal-and how those associations differ
      with age. Results from multilevel models revealed that familiarity, importance,
      type of social partner, and gender composition of the social context were
      associated with affect valence and/or affect arousal. Higher familiarity, higher
      importance, and same-gender composition were associated with more positive affect
      valence and higher arousal. Interactions with family and friends were linked to
      more positive valence whereas nonfamily social partners were linked to higher
      arousal. Age moderated the associations between importance and affect arousal,
      and between type of social partner and both dimensions of core affect. Findings
      align with theoretical propositions, contributing to but also suggesting need for
      further precision regarding how development shapes the interplay between social
      context and moment-to-moment affective experience. (PsycINFO Database Record

PMID- 27869468
TI  - Termination in cognitive-behavioral therapy with children, adolescents, and
      parents.
AB  - The process of terminating cognitive-behavioral therapy (CBT) with families has
      been largely neglected in the literature, with the limited research focused on
      premature termination. This article describes the natural termination process in
      CBT with children, adolescents, and their parents. Based on existing theories, we
      describe a cognitive-behavioral model for: (a) initiating and engaging in
      discussion of termination, (b) processing the termination of treatment and the
      therapeutic relationship, (c) key aspects of the termination process in the final
      session, and (d) the very end of the final session (saying goodbye). For each of
      the 4 components, we review relevant theories, provide clinical exchanges to
      demonstrate techniques, and provide related research support. (PsycINFO Database
      Record

PMID- 27869469
TI  - Saying good goodbyes to your clients: A functional analytic psychotherapy (FAP)
      perspective.
AB  - Functional analytic psychotherapy (FAP) promotes client growth by shaping
      clients' daily life problems that also show up in session with their therapists.
      FAP therapists create evocative contexts within therapy that afford clients the
      opportunity to practice, refine, and be reinforced for new, more adaptive
      behaviors which then can be generalized into their outside lives. In FAP, the
      termination process will vary from client to client depending on the nature of
      the client's problems and targets. For many clients, the process can be a rich,
      multifaceted, final opportunity to evoke, reinforce, and promote generalization
      of clients' in-session improvements, particularly improvements related to
      vulnerable self-expression in the service of intimate and close relationships. By
      making explicit agreements at the outset of therapy to participate in an
      intentional termination process, and by later providing an evocative structure
      for ending therapy with vulnerable emotional expression, clients have the
      opportunity to develop more adaptive behaviors in the context of relationship
      endings which can be a painful part of the human experience. Equipped with the
      skills of open-hearted communication developed from an authentic relationship
      with their therapist, clients can leave therapy on a trajectory of further growth
      in interpersonal connection and living more boldly. (PsycINFO Database Record

PMID- 27869470
TI  - Terminating supervision.
AB  - The focus of this paper is on the termination of clinical supervision. Although
      clinical supervision is considered the backbone of most mental health training
      programs, it gets relatively little theoretical or empirical attention. The
      termination of supervision has received even less attention. In this paper, we
      describe an approach to terminating supervision in our treatment team, which
      integrates intensive assessment with a relational perspective in a clinical
      science training program (Levendosky & Hopwood, 2016). We describe our
      established conceptual framework, review empirical evidence, and provide verbatim
      examples from final supervision meetings on our team to elaborate the importance
      of conceptualizing individual differences across trainees and parallels between
      supervision and psychotherapy dynamics. We conclude by emphasizing the need for
      research on supervision in general and supervision termination in particular.
      (PsycINFO Database Record

PMID- 27869471
TI  - A collaborative approach to psychotherapy termination.
AB  - Collaboration has been recognized as an important relationship variable in
      psychotherapy that is linked to client treatment outcomes. Although many
      therapists seek to build a collaborative working relationship with their clients
      when making treatment decisions, collaboration is also an important technique
      that can be used to help clients plan for a successful termination. Collaborative
      termination strategies can first be used in the initial session in order to
      address clients' termination expectations. Strategies can also be used throughout
      treatment to help clients focus on their treatment goals. Last, collaborative
      termination strategies should be used in the final session to help clients take
      ownership of their gains and to equalize the therapeutic relationship. In this
      article, we provide specific recommendations for collaborating with clients in
      preparing for psychotherapy termination. Case examples demonstrating these
      strategies are also provided. (PsycINFO Database Record

PMID- 27869472
TI  - Patients' affective processes within initial experiential dynamic therapy
      sessions.
AB  - Research has indicated that patients' in-session experience of previously avoided
      affects may be important for effective psychotherapy. The aim of this study was
      to investigate patients' in-session levels of affect experiencing in relation to
      their corresponding levels of insight, motivation, and inhibitory affects in
      initial Experiential Dynamic Therapy (EDT) sessions. Four hundred sixty-six 10
      min video segments from 31 initial sessions were rated using the Achievement of
      Therapeutic Objectives Scale. A series of multilevel growth models, controlling
      for between-therapist variability, were estimated to predict patients' adaptive
      affect experiencing (Activating Affects) across session segments. In line with
      our expectations, higher within-person levels of Insight and Motivation related
      to higher levels of Activating Affects per segment. Contrary to expectations,
      however, lower levels of Inhibition were not associated with higher levels of
      Activating Affects. Further, using a time-lagged model, we did not find that the
      levels of Insight, Motivation, or Inhibition during one session segment predicted
      Activating Affects in the next, possibly indicating that 10-min segments may be
      suboptimal for testing temporal relationships in affective processes. Our results
      suggest that, to intensify patients' immediate affect experiencing in initial EDT
      sessions, therapists should focus on increasing insight into defensive patterns
      and, in particular, motivation to give them up. Future research should examine
      the impact of specific inhibitory affects more closely, as well as between
      therapist variability in patients' in-session adaptive affect experiencing.
      (PsycINFO Database Record

PMID- 27869473
TI  - The headwinds/tailwinds asymmetry: An availability bias in assessments of
      barriers and blessings.
AB  - Seven studies provide evidence of an availability bias in people's assessments of
      the benefits they've enjoyed and the barriers they've faced. Barriers and
      hindrances command attention because they have to be overcome; benefits and
      resources can often be simply enjoyed and largely ignored. As a result of this
      "headwind/tailwind" asymmetry, Democrats and Republicans both claim that the
      electoral map works against them (Study 1), football fans take disproportionate
      note of the challenging games on their team's schedules (Study 2), people tend to
      believe that their parents have been harder on them than their siblings are
      willing to grant (Study 3), and academics think that they have a harder time with
      journal reviewers, grant panels, and tenure committees than members of other
      subdisciplines (Study 7). We show that these effects are the result of the
      enhanced availability of people's challenges and difficulties (Studies 4 and 5)
      and are not simply the result of self-serving attribution management (Studies 6
      and 7). We also show that the greater salience of a person's headwinds can lead
      people to believe they have been treated unfairly and, as a consequence, more
      inclined to endorse morally questionable behavior (Study 7). Our discussion
      focuses on the implications of the headwind/tailwind asymmetry for a variety of
      ill-conceived policy decisions. (PsycINFO Database Record

PMID- 27869474
TI  - Coming in 2017: Our 15th Anniversary!

PMID- 27869475
TI  - How Biobanks Are Assessing and Measuring Their Financial Sustainability.
AB  - As guest editors of this sustainability issue of Biopreservation and Biobanking
      focused on business planning, utilization, and marketing, we invited a number of
      experts from different sectors of the biobanking arena to provide their views on
      business planning issues. Each expert was asked to provide a brief background
      statement on their biobanks, to build a context to understand their answers to
      the sustainability questions. We hope that these insights and experiences can
      provide valuable considerations and ideas for other biobanks who wish to develop
      or refine their own business plans, measure their utilization rates, and work
      toward financial sustainability. In addition, after the expert input was
      gathered, the guest editors invited an additional expert to provide summary
      comments and observations on cost and operational optimization strategies. The
      broad experiences from all of the experts included and scope of the biobanks they
      represent should provide a level of relevant representation for all interested
      parties.

PMID- 27869476
TI  - Low-level laser therapy effectiveness in accelerating orthodontic tooth movement:
      A randomized controlled clinical trial.
AB  - OBJECTIVE: To evaluate the effectiveness of low-level laser therapy (LLLT) in
      accelerating orthodontic tooth movement of crowded maxillary incisors. MATERIALS
      AND METHODS: This two-arm, parallel-group, randomized controlled trial involved
      26 patients with severe to extreme maxillary incisors irregularity according to
      Little's irregularity index, indicating two first premolars extraction. Patients
      were randomly assigned to either the laser group or the control group (13 each).
      Following premolars extraction, orthodontic treatment with fixed appliances was
      initiated for both groups. Immediately after insertion of the first archwire,
      patients in the laser group received a LLL dose from an 830-nm wavelength Ga-Al
      As semiconductor laser device with energy of 2 J/point. The laser was applied to
      each maxillary incisor's root at four points (two buccal, two palatal).
      Application was repeated on days 3, 7, 14, and then every 15 days starting from
      the second month until the end of the leveling and alignment stage. Alignment
      progress was evaluated on the study casts taken before inserting the first
      archwire (T0), after 1 month of treatment commencement (T1), after 2 months (T2),
      and at the end of the leveling and alignment stage (T3). The outcome measures
      were the overall time needed for leveling and alignment and the leveling and
      alignment improvement percentage. RESULTS: A statistically significant difference
      was found between the two groups in the overall treatment time (P < .001) and the
      leveling and alignment improvement percentage at T1 (P = .004) and T2; (P =
      .001). CONCLUSION: LLLT is an effective method for accelerating orthodontic tooth
      movement.

PMID- 27869479
TI  - The 2017 ISBER Annual Meeting & Exhibits in Toronto "Due North: Aligning
      Biobanking Practice with Evolving Evidence and Innovation".

PMID- 27869477
TI  - A Review of Living Collections with Special Emphasis on Sustainability and Its
      Impact on Research Across Multiple Disciplines.
AB  - Formal living collections have unique characteristics that distinguish them from
      other types of biorepositories. Comprising diverse resources, microbe culture
      collections, crop and biodiversity plant germplasm collections, and animal
      germplasm repositories are commonly allied with specific research communities or
      stakeholder groups. Among living collections, microbial culture collections have
      very long and unique life histories, with some being older than 100 years.
      Regulatory, financial, and technical developments have impacted living
      collections in many ways. International treaty obligations and restrictions on
      release of genetically modified organisms complicate the activities of living
      collections. Funding for living collections is a continuing challenge and
      threatens to create a two-tier system where medically relevant collections are
      well funded and all other collections are underfunded and hence understaffed.
      Molecular, genetic, and whole genome sequence analysis of contents of microbes
      and other living resource collections bring additional value to living
      collections.

PMID- 27869478
TI  - Etravirine and Rilpivirine Drug Resistance Among HIV-1 Subtype C Infected
      Children Failing Non-Nucleoside Reverse Transcriptase Inhibitor-Based Regimens in
      South India.
AB  - We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV
      infected children who were identified as failing first-line therapy that included
      first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at
      least 6 months. We found that 54% and 65% of the children had genotypically
      predicted resistance to second-generation non-nucleoside RT inhibitors drugs
      Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations
      may compromise future NNRTI-based regimens, especially in resource-limited
      settings. To complement these investigations, we also analyzed the sequences in
      Stanford database, Monogram weighted score, and DUET weighted score algorithms
      for ETR susceptibility and found almost perfect agreement between the three
      algorithms in predicting ETR susceptibility from genotypic data.

PMID- 27869481
TI  - Papillary vs Nonpapillary Puncture in Percutaneous Nephrolithotomy: A Prospective
      Randomized Trial.
AB  - INTRODUCTION: Literature suggests that the percutaneous punctures for
      percutaneous nephrolithotomy (PCNL) must be performed at the papilla of the renal
      calix and a puncture at the infundibulum or the direction of the pelvis is not
      advisable because of increased hemorrhagic risk. A prospective randomized study
      was conducted to investigate the safety in terms of blood loss of the
      infundibular approach for PCNL. MATERIALS AND METHODS: Patients with renal stones
      with an accumulative size of at least 2 cm were randomly assigned to one of two
      parallel groups to undergo PCNL with either papillary (Group 1) or infundibular
      (Group 2) renal access. The primary outcome measures were the reduction in
      hemoglobin on first postoperative day and the need for transfusion during the
      first postoperative month. Secondary endpoints included the operative and
      fluoroscopy time, number of accesses performed, overall complication rate,
      hospitalization time, and complications up to 3 months. RESULTS: In total, 27 and
      28 patients were enrolled in Groups 1 and 2, respectively. Patient age, body mass
      index, and stone size were similar among the groups (p = 0.672, 0.256, and 0.889,
      respectively). Reduction in hemoglobin and transfusion rate did not differ among
      Groups 1 and 2 (p = 0.916, p = 1.0, respectively). Operative time was higher in
      the case of Group 1 (p = 0.027). The overall complications rate was 7.4% for
      Group 1 and 7.14% for Group 2. Hospitalization time was not significantly
      different in the study groups (p = 0.724). CONCLUSIONS: The infundibular approach
      for PCNL to the posterior middle renal calices is not associated with higher
      blood loss or transfusion rate in comparison with the respective approach to the
      fornix of the papilla when the currently described technique is performed.

PMID- 27869480
TI  - Caregiver profiles in dementia related to quality of life, depression and
      perseverance time in the European Actifcare study: the importance of social
      health.
AB  - OBJECTIVES: To identify caregiver profiles of persons with mild to moderate
      dementia and to investigate differences between identified caregiver profiles,
      using baseline data of the international prospective cohort study Actifcare.
      METHODS: A latent class analysis was used to discover different caregiver
      profiles based on disease related characteristics of 453 persons with dementia
      and their 453 informal caregivers. These profiles were compared with regard to
      quality of life (CarerQoL score), depressive symptoms (HADS-D score) and
      perseverance time. RESULTS: A 5-class model was identified, with the best
      Bayesian Information Criterion value, significant likelihood ratio test (p <
      0.001), high entropy score (0.88) and substantive interpretability. The classes
      could be differentiated on two axes: (i) caregivers' age, relationship with
      persons with dementia, severity of dementia, and (ii) tendency towards stress and
      difficulty adapting to stress. Classes showed significant differences with all
      dependent variables, and were labelled 'older low strain', 'older intermediate
      strain', 'older high strain', 'younger low strain' and 'younger high strain'.
      CONCLUSION: Differences exist between types of caregivers that explain
      variability in quality of life, depressive symptoms and perseverance time. Our
      findings may give direction for tailored interventions for caregivers of persons
      with dementia, which may improve social health and reduce health care costs.

PMID- 27869482
TI  - Clinical trial transparency update: an assessment of the disclosure of results of
      company-sponsored trials associated with new medicines approved in Europe in
      2013.
AB  - BACKGROUND: The objective of this study was to assess the timely disclosure of
      results of company-sponsored clinical trials related to all new medicines
      approved by the European Medicines Agency (EMA) during 2013. This is an extension
      of two previously reported studies of trials related to all new medicines
      approved in Europe in 2009, 2010 and 2011, and in 2012. The original study found
      that over a three year period over three-quarters of all trials were disclosed
      within 12 months and almost 90% were disclosed by the end of the study. The
      extension study (2012 approvals) showed an improvement in results disclosure
      within 12 months to 90%, and an overall disclosure rate of 92% by the end of the
      study. METHODS: The methodology used was exactly as previously reported. Various
      publicly available information sources were searched for both clinical trial
      registration and disclosure of results. All completed company-sponsored trials
      related to each new medicine approved for marketing by the EMA in 2013, carried
      out in patients and recorded on a clinical trials registry and/or included in an
      EMA European Public Assessment Report (EPAR), were included. Information sources
      were searched between 1 May and 31 July 2015. OUTCOME MEASURES AND RESULTS: The
      main outcome measure was the proportion of trials for which results had been
      disclosed on a registry or in the scientific literature either within 12 months
      of the later of either first regulatory approval or trial completion, or by 31
      July 2015 (end of survey). Of the completed trials associated with 34 new
      medicines licensed to 24 different companies in 2013, results of 90% (484/539)
      had been disclosed within 12 months, and results of 93% (500/539) had been
      disclosed by 31 July 2015. CONCLUSIONS: The disclosure rate within 12 months of
      90% suggests that industry is continuing to achieve disclosure in a timely
      manner. The overall disclosure rate at study end of 93% indicates that the
      improvement in transparency amongst company-sponsored trials has been maintained
      in the trials associated with new medicines approved in 2013.

PMID- 27869484
TI  - Two new monoterpenes from Sibiraea laevigata.
AB  - Two new monoterpenes, 3-(2-oxo-4-methyl-3-pentenyl)furan-5H-2-one (1) and 3-[(2E)
      4-hydroxyl-4-methyl-2-pentenyl)]furan-5H-2-one (2), along with eight known
      compounds (3-10), were isolated from the stalks and infructescence of Sibiraea
      laevigata. Their structures were elucidated by spectroscopic methods including
      extensive 1D and 2D NMR techniques. In addition, all of these isolates were
      evaluated for their cytotoxic and antioxidant activities. The results showed that
      compounds 5-7 displayed cytotoxicity with IC50 values ranging from 34.8 to 43.2
      MUg ml-1 against tumor cell lines. Furthermore, 5 and 9 showed antioxidant
      activities.

PMID- 27869485
TI  - The Practice of Hatha Yoga for the Treatment of Pain Associated with
      Endometriosis.
AB  - OBJECTIVES: The aim of this study was to compare chronic pelvic pain, menstrual
      patterns, and quality of life (QoL) in two groups of women with endometriosis:
      those who did and those who did not participate in a specific 8-week yoga
      intervention. METHOD: This was a randomized controlled trial. It was conducted at
      the University of Campinas Medical School, Campinas, SP, Brazil. Forty women were
      randomly divided into two groups: an intervention group of women who practiced
      yoga (n = 28), and a control group of women who did not practice yoga (n = 12).
      Participants attended 90-min scheduled yoga sessions twice a week for 8 weeks.
      Additionally, an Endometriosis Health Profile (EHP)-30 questionnaire was applied
      to evaluate women's QoL at admission and 2 months later upon completion of the
      yoga program. Menstrual and daily pain patterns were evaluated through a daily
      calendar (visual analog scale). RESULTS: The degree of daily pain was
      significantly lower among the women who practiced yoga compared with the non-yoga
      group (p = 0.0007). There was an improvement of QoL in both groups between
      baseline and the end of the study evaluation. In relation to EHP-30 domains, pain
      (p = 0.0046), impotence (p = 0.0006), well-being (p = 0.0009), and image (p =
      0.0087) from the central questionnaire, and work (p = 0.0027) and treatment (p =
      0.0245) from the modular questionnaire were significantly different between the
      study groups over time. There was no significant difference between the two
      groups regarding the diary of menstrual patterns (p = 0.96). CONCLUSIONS: Yoga
      practice was associated with a reduction in levels of chronic pelvic pain and an
      improvement in QoL in women with endometriosis.

PMID- 27869487
TI  - The incidence of incisional hernias following ileostomy reversal in colorectal
      cancer patients treated with anterior resection.
AB  - INTRODUCTION The aim of this study was to identify the rate of incisional hernia
      formation following ileostomy reversal in patients who underwent anterior
      resection for colorectal cancer. In addition, we aimed to ascertain risk factors
      for the development of reversal-site incisional hernias and to record the
      characteristics of the resultant hernias. MATERIALS AND METHODS Using a
      prospectively compiled database of colorectal cancer patients who were treated
      with anterior resection, we identified individuals who had undergone both
      ileostomy formation and subsequent reversal of their ileostomies from January
      2005 to December 2014. Medical records were reviewed to record descriptive
      patient data about risk factors for hernia formation, operative details and any
      subsequent operations. Computed tomography reports were reviewed to identify the
      number, site and characteristics of incisional hernias. RESULTS A total of 121
      patients were included in this study; 14.9% (n = 18) developed an incisional
      hernia at the ileostomy reversal site; 17.4% (n = 21) at a non-ileostomy site and
      6.6% (n = 8) developed both. The reversal-site hernias were smaller both in width
      and length compared with the non-ileostomy-site hernias. Risk factors for the
      development of reversal-site incisional hernias were higher body mass index
      (BMI), lower age, open surgery, longer reversal time and a history of previous
      hernias. We did not detect a difference in the size of the incisional hernias
      that developed in patients with these specific risk factors. CONCLUSIONS
      Incisional hernias are a significant complication of ileostomy reversal. Further
      evaluation of the use of prophylactic mesh to reduce the incidence of incisional
      hernias may be worthwhile.

PMID- 27869488
TI  - A randomised controlled trial assessing the efficacy of co-phenylcaine nasal
      spray in flexible transnasal pharyngolaryngoscopy.
AB  - INTRODUCTION The aim of this study was to assess whether using co-phenylcaine
      nasal spray before flexible transnasal pharyngolaryngoscopy results in reduced
      pain and discomfort during the procedure. METHODS This was a randomised
      controlled trial. Eighty-four patients were randomised to receive either co
      phenylcaine nasal spray or placebo nasal spray before performing transnasal
      flexible pharyngolaryngoscopy. Patient reported outcome measures included pain,
      discomfort, unpleasantness and willingness to repeat the procedure while
      clinician reported outcome measures comprised ease of examination and quality of
      view obtained during the procedure. RESULTS There was no statistically
      significant difference in scores for pain, discomfort, unpleasantness and
      willingness to repeat the procedure between the co-phenylcaine and placebo
      groups. On the other hand, ease of examination scores were significantly better
      for the co-phenylcaine group than for the placebo group. CONCLUSIONS The majority
      of patients do not find flexible pharyngolaryngoscopy unpleasant or painful with
      or without topical nasal anaesthesia. However, the spray does appear to help the
      examiner in completing a satisfactory assessment.

PMID- 27869486
TI  - Enucleation versus hepatectomy for giant hepatic haemangiomas: a meta-analysis.
AB  - INTRODUCTION Hepatic haemangiomas are the most common benign liver tumours. They
      can be treated with surgical resection such as enucleation or hepatectomy if
      necessary. However, controversy remains over the clinical outcome and safety of
      these two methods. In this study, we performed a comprehensive meta-analysis to
      compare the efficacy of liver resection with enucleation for giant haemangiomas.
      METHODS The online databases PubMed, Embase and CNKI (China National Knowledge
      Infrastructure) were searched for relevant original articles. We compared
      operation time, blood loss, transfusion requirements, inflow occlusion time and
      postoperative complications between enucleation and hepatectomy. RESULTS Seven
      controlled clinical trials met the predefined inclusion criteria. Analysis
      indicated that the enucleation group had significantly shorter operation time
      (weighted mean difference, WMD -28.22, 95% confidence interval, CI, -54.82 to 
      1.62), less blood loss (WMD -395.92, 95% CI -521.25 to -270.58) and fewer
      complications (odds ratio, OR, 0.47, 95 % CI 0.34 to 0.65). There were no
      significant differences between enucleation and hepatectomy with regard to
      transfusion requirements (OR 0.61, 95% CI 0.22 to 1.68) and inflow occlusion time
      (WMD 7.91, 95% CI -5.62 to 21.44). CONCLUSIONS Enucleation has advantages over
      hepatectomy in relation to operation time, blood loss and complications.
      Enucleation is a safe and effective treatment for giant hepatic haemangioma.

PMID- 27869483
TI  - The epigenetic impacts of social stress: how does social adversity become
      biologically embedded?
AB  - Epigenetic mechanisms are implicated in the processes through which social
      stressors erode health in humans and other animals. Here I review progress in
      elucidating the biological pathways underlying the social gradient in health,
      with particular emphasis on how behavioral stresses influence epigenomic
      variation linked to health. The evidence that epigenetic changes are involved in
      embedding of social status-linked chronic stress is reviewed in the context of
      current knowledge about behavior within animal dominance hierarchies and the
      impacts of social position on behaviors that affect health. The roles of
      epigenetic mechanisms in responses to trauma and the evidence for their
      involvement in intergenerational transmission of the biological impacts of
      traumatic stress are also considered. Taken together, the emerging insights have
      important implications for development of strategies to improve societal health
      and well-being.

PMID- 27869489
TI  - An atypical presentation of necrotising fasciitis.
AB  - Necrotising fasciitis is a rare infection with a high mortality rate. Clinical
      manifestation may be influenced by an underlying disease state. We report a case
      of a 70-year-old man with an anaplastic large-cell lymphoma who presented with
      inconclusive signs of necrotising fasciitis following a neutropenic phase after
      chemotherapy. Surgical exploration did not reveal the typical macroscopic
      features of necrotising fasciitis. Microbiological investigations revealed
      Escherichia coli. The lack of massive tissue inflammation, probably due to the
      neutropenia in our patient, has not been described by other authors. Diagnostic
      uncertainties owing to masked or uncharacteristic signs in immune compromised
      patients may lead to a delayed surgical debridement, of which clinicians should
      be aware.

PMID- 27869490
TI  - Congenital diaphragmatic hernia causing cardiac arrest in a 30-year-old woman.
AB  - Congenital diaphragmatic hernia (CDH) usually presents in infancy with
      respiratory failure requiring urgent surgical correction. Mortality in this group
      of patients remains poor and persistent pulmonary hypertension is a significant
      contributor. It is therefore rare for patients to reach adulthood undiagnosed.
      CDH is often identified incidentally in adults but when symptoms arise, they
      relate to the organ involved, and include gastrointestinal symptoms of dyspepsia
      and obstruction, as well as respiratory complaints such as dyspnoea. We present
      the case of a 30-year-old woman who was admitted with non-specific symptoms of
      upper abdominal discomfort but whose deteriorating condition culminated in a
      cardiac arrest, as an unreported presentation of CDH. The patient presented
      initially with severe left upper quadrant pain. Her chest x-ray on admission
      suggested a raised left hemidiaphragm. She went on to have computed tomography
      (CT) of the thorax and abdomen as well as oesophagogastroduodenoscopy, which
      raised the suspicion of diaphragmatic eventration. Repeat CT was performed after
      the patient collapsed on the ward five days following admission, revealing
      tracheal deviation, and a strangulated Bochdalek hernia containing stomach and
      spleen. After transfer to the anaesthetic room, she suffered a cardiac arrest.
      Advanced life support was required to return spontaneous cardiac function. She
      was intubated and ventilated, and a needle thoracostomy was performed to
      decompress the tension gastrothorax. Emergency laparotomy revealed a gangrenous
      stomach and spleen. Total gastrectomy with primary Roux-en-Y reconstruction,
      splenectomy and insertion of a feeding jejunostomy were performed. The patient
      recovered well postoperatively and was discharged two weeks following surgery.

PMID- 27869491
TI  - Self injection of foreign materials into the penis.
AB  - Injection of the subcutaneous tissues of the penis for enlargement of penile
      girth has been practised for many years by laypeople and medical practitioners
      alike. However, with recognition of the complications, the practice has died out.
      We report a series of five patients who presented having injected foreign
      materials into the subcutaneous tissues of their penises, including paraffin and
      mineral oils. Our patients had a variable time course of presentation ranging
      from 1 day following injection to over 26 years. Self-injection of the
      subcutaneous tissues of the penis is an unusual presentation for a penile mass
      but should be considered as a differential diagnosis in patients with a long
      latent period to presentation or with characteristic magnetic resonance imaging
      and histological appearances.

PMID- 27869492
TI  - Risk factors for development of primary bladder squamous cell carcinoma.
AB  - INTRODUCTION The aim of this study was to investigate the prevalence of risk
      factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A
      total of 90 cases of primary SCC of the bladder were identified through
      multicentre analysis. Patient demographics, stage and grade of cancer at
      presentation, management and outcomes were recorded. The presence of known risk
      factors (catheter use, neuropathic bladder, smoking history, recurrent urinary
      tract infection and bladder stones) was also documented. RESULTS Over half of the
      patients had at least one identifiable risk factor for the development of primary
      bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent
      self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic
      bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of
      recurrent urinary tract infection. Statistical analysis of the results showed no
      association between risk factors and grade of tumour at presentation. CONCLUSIONS
      These data further support the association between primary bladder SCC and
      several of the well documented risk factors for its development. Chronic use of
      CISC may confer a greater risk for development of SCC than thought previously.
      Further evidence of the role of CISC in primary SCC is required to justify
      routine screening and to determine exactly when surveillance of the bladder
      should begin for this group of patients.

PMID- 27869493
TI  - Laparoscopy-assisted gastrectomy in the elderly: experience from a UK centre.
AB  - BACKGROUND Gastric cancer has a high incidence in the elderly in the UK, with a
      significant number of patients aged 75 years or more. While surgery forms the
      mainstay of treatment, evidence pertaining to the management of gastric cancer in
      the Western population in this age group is scarce. METHODS We retrospectively
      reviewed the outcomes of laparoscopy-assisted total and distal gastrectomies at
      our centre from 2005 to 2015. Patients aged 70 years or above were included in
      the elderly group. RESULTS A total of 60 patients underwent laparoscopy-assisted
      gastrectomy over a 10-year period, with a predominance of male patients. There
      was no significant difference in the rate of overall surgical and non-surgical
      complications, in-hospital mortality, operation time and length of hospital stay,
      between the elderly and non-elderly groups. Univariate analysis, performed for
      risk factors relating to anastomotic leak and surgical complications, showed that
      age over 70 years and higher American Association of Anesthesiologists grades are
      associated with a higher, though not statistically significant, number of
      anastomotic leaks (P = 1.000 and P = 0.442, respectively) and surgical
      complications (P = 0.469 and P = 0.162, respectively). The recurrence rate within
      the first 3 years of surgery was significantly higher in the non-elderly group
      compared with the elderly group (Log Rank test, P = 0.002). There was no
      significant difference in survival between the two groups (Log Rank test, P =
      0.619). CONCLUSIONS Laparoscopy-assisted gastrectomy is safe and feasible in an
      elderly population. There is a need for well-designed, prospective, randomised
      studies with quality of life data to inform our practice in future.

PMID- 27869494
TI  - Necrotising fasciitis caused by metastatic endometrial cancer: a rare cause of a
      life-threatening condition.
AB  - We report a case of necrotising fasciitis caused by metastatic endometrial
      adenocarcinoma. Metastases to the lumbar spine with local invasion to the
      iliopsoas muscle led to an iliopsoas abscess, which subsequently progressed to
      necrotising fasciitis of the flank. This patient lacked common risk factors for
      necrotising fasciitis. There are no previous reports in the literature of
      necrotising fasciitis with this aetiology. We discuss the available evidence for
      aetiology of and risk factors for necrotising fasciitis, and the relation of time
      to surgery with prognosis.

PMID- 27869495
TI  - A comparison of airborne bacterial fallout between orthopaedic and vascular
      surgery.
AB  - INTRODUCTION The objective of the study was to compare bacterial fallout during
      vascular prosthesis insertion and orthopaedic major joint replacement performed
      in conventional and laminar flow ventilation, respectively. MATERIALS AND METHODS
      A prospective single-centre case control study of 21 consecutive elective
      vascular procedures involving prosthetic graft insertion and 24 consecutive
      elective orthopaedic major joint replacements were tested for degree of bacterial
      fallout using agar settle plates. Preparation time, waiting time and total
      procedure duration were collected at the time of surgery, and bacterial colony
      counts on the agar settle plates from airborne bacterial fallout were counted
      after an incubation period. RESULTS Bacterial fallout count in vascular
      prosthetic graft insertion was 15-fold greater than in orthopaedic prosthetic
      joint insertion (15, (IQR 15) vs 1, (IQR 3) respectively, P < 0.0001, Wilcoxon).
      Waiting time and patient transfer did not significantly increase bacterial
      fallout counts during the procedure (P = 0.9). CONCLUSIONS Vascular surgical
      theatres have significantly higher bacterial fallout compared with orthopaedic
      theatres. This may be partly explained by orthopaedic surgery being routinely
      performed in laminar flow ventilation, a practice which has not been widely
      adopted for vascular surgery, in which prosthetic infection may also result in
      significant mortality and morbidity.

PMID- 27869497
TI  - Appendicular abscess as an unprecedented cause of an inferior lumbar hernia.
AB  - Inferior lumbar hernias are uncommon hernias resulting from a defect in the
      abdominal wall. They can occur during infancy (congenital defect), albeit less
      frequently, or spontaneously after trauma or surgery with a lumbar incision. With
      fewer than 300 cases reported over the past 3 centuries, clinical diagnosis is
      often confusing owing to non-specific symptoms, relating to the gastrointestinal,
      genitourinary or musculoskeletal systems. We present a case of an inferior lumbar
      hernia following spontaneous rupture of a retrocaecally tracked appendicular
      abscess and a brief literature review.

PMID- 27869496
TI  - A systematic review of the prognostic value of lymph node ratio, number of
      positive nodes and total nodes examined in pancreatic ductal adenocarcinoma.
AB  - BACKGROUND Pancreatic ductal adenocarcinoma is the most common pancreatic cancer.
      Five-year overall survival is currently 3.3-6.0%. The aim of this review was to
      evaluate the prognostic value of lymph node ratio, number of positive nodes and
      total nodes examined on overall survival rate following pancreatic resection.
      MATERIALS AND METHODS A literature search was conducted of MEDLINE, EMBASE, the
      Cochrane Library and Central Register of Controlled Trials and the Cochrane
      Database of Systematic Review databases, from January 1996 to January 2016.
      RESULTS Overall, 19 studies including 4,883 patients examined the relationship
      between lymph node ratio and overall survival. A high lymph node ratio was
      associated with decreased overall survival in 17 studies. A total of 12 studies
      examined the relationship between the number of positive nodes and overall
      survival, and 11 studies revealed that an increase in the number of positive
      nodes was associated with decreased overall survival. In 15 studies examining the
      relationship between the total nodes examined and overall survival, there was no
      association with overall survival in 12 studies. CONCLUSIONS Lymph node ratio and
      number of positive nodes are factors associated with overall survival in
      pancreatic ductal adenocarcinoma, but not total nodes examined.

PMID- 27869498
TI  - An Intervention With Meaning.
AB  - BACKGROUND: The Veterans Health Administration (VHA) health-care system utilizes
      a multilevel suicide prevention intervention that features the use of
      standardized safety plans with veterans considered to be at high risk for
      suicide. AIMS: Little is known about clinician perceptions on the value of safety
      planning with veterans at high risk for suicide. METHOD: Audio-recorded
      interviews with 29 VHA behavioral health treatment providers in a southeastern
      city were transcribed and analyzed using qualitative methodology. RESULTS:
      Clinical providers consider safety planning feasible, acceptable, and valuable to
      veterans at high risk for suicide owing to the collaborative and interactive
      nature of the intervention. Providers identified the types of veterans who easily
      engaged in safety planning and those who may experience more difficulty with the
      process. CONCLUSION: Additional research with VHA providers in other locations
      and with veteran consumers is needed.

PMID- 27869499
TI  - Capsaicinoids improve egg production by regulating ovary nuclear transcription
      factors against heat stress in quail.
AB  - 1. To examine the molecular mechanism of capsaicinoid supplementation from
      capsicum extract, laying Japanese quail (n = 180, 5 weeks old) were reared either
      at 22 degrees C for 24 h/d (thermoneutral, TN) or at 34 degrees C for 8 h/d (heat
      stress, HS) and fed on one of three diets containing 0, 25 or 50 mg of
      capsaicinoids per kilogram for 12 weeks (2 * 3 factorial arrangement). 2. The
      results revealed that exposure to HS decreased feed consumption by 10.7% and egg
      production by 13.6%, increased serum and ovary malondialdehyde (MDA) levels by
      66.9% and 88.1%, respectively, and reduced ovary superoxide dismutase (SOD),
      catalase (CAT) and glutathione peroxidase (GSH-Px) activities by 28.3%, 48.7% and
      43.8%, respectively. 3. There were magnifications in the ovary nuclear factor
      kappa-light-chain-enhancer of activated B cell (NF-kappaB) levels by 42.4% and
      suppressions in nuclear factor (erythroid-derived 2)-like 2 (Nrf2), protein
      kinase B (Akt) and haem-oxygenase 1 (HO-1) levels by 29.2%, 38.2% and 30.7%,
      respectively, in heat-stressed quail. 4. With increasing supplemental
      capsaicinoids, there were linear increases in egg production, antioxidant enzyme
      activity, linear decreases in ovary MDA and NF-kappaB levels and linear increases
      in ovary Nrf2, Akt and HO-1 levels at a greater extent in quail reared under TN
      condition than those reared under HS condition. Two-way treatment interactions
      showed that the degree of restorations in all response variables was more notable
      under the HS environment than under the TN environment as supplemental
      capsaicinoid level was increased. 5. In conclusion, capsaicinoid supplementation
      alleviates oxidative stress through regulating the ovary nuclear transcription
      factors in heat-stressed quail.

PMID- 27869500
TI  - Lower Frailty Is Associated with Successful Cognitive Aging Among Older Adults
      with HIV.
AB  - Aging with HIV poses unique and complex challenges, including avoidance of
      neurocognitive disorder. Our objective here is to identify the prevalence and
      predictors of successful cognitive aging (SCA) in a sample of older adults with
      HIV. One hundred three HIV-infected individuals aged 50 and older were recruited
      from the Modena HIV Metabolic Clinic in Italy. Participants were treated with
      combination antiretroviral therapy for at least 1 year and had suppressed plasma
      HIV viral load. SCA was defined as the absence of neurocognitive impairment (as
      defined by deficits in tasks of episodic learning, information processing speed,
      executive function, and motor skills) depression, and functional impairment
      (instrumental activities of daily living). In cross-sectional analyses, odds of
      SCA were assessed in relation to HIV-related clinical data, HIV-Associated Non
      AIDS (HANA) conditions, multimorbidity (>=2HANA conditions), and frailty. A
      frailty index was calculated as the number of deficits present out of 37 health
      variables. SCA was identified in 38.8% of participants. Despite no differences in
      average chronologic age between groups, SCA participants had significantly fewer
      HANA conditions, a lower frailty index, and were less likely to have
      hypertension. In addition, hypertension (odds ratio [OR] = 0.40, p = .04),
      multimorbidity (OR = 0.35, p = .05), and frailty (OR = 0.64, p = .04) were
      significantly associated with odds of SCA. Frailty is associated with the
      likelihood of SCA in people living with HIV. This defines an opportunity to apply
      knowledge from geriatric population research to people aging with HIV to better
      appreciate the complexity of their health status.

PMID- 27869501
TI  - Shared decision-making in dementia care planning: barriers and facilitators in
      two European countries.
AB  - BACKGROUND: Shared decision-making (SDM) is a means of allowing people with
      dementia to take part in making choices, be autonomous and participate in social
      activities. Involving them in SDM is an important way of promoting social health.
      However, including families and dementia residents in decision-making can be
      challenging for care staff working in nursing homes. The objective of this study
      was to identify barriers and facilitators regarding the implementation of an SDM
      framework for care planning in two nursing homes, one in Italy and one in the
      Netherlands. METHODS: Focus group interviews were conducted with healthcare
      professionals who, after being trained, applied the SDM framework. Content
      analysis was used to analyze the data. RESULTS: Six months after the feasibility
      trial, focus group interviews with healthcare professionals (n = 10 in Italy; n =
      9 in the Netherlands) were held. We found 6 themes and 15 categories. Within
      these themes, facilitators and barriers were identified. The categories of team
      collaboration, communication skills and nursing home policy were found to be
      facilitators to the implementation process, whereas regulations, lack of funding
      and of involvement of family caregivers were the main barriers. Family attitudes
      towards SDM could be both. The main difference between countries concerned the
      residents' cognitive status that influenced their degree of involvement.
      CONCLUSION: Communication skills training for professionals, training of family
      caregivers, and involvement of the management in the implementation process seem
      to be crucial factors in successfully implementing SDM in nursing homes, and
      increasing the involvement of families and dementia residents in decision-making.

PMID- 27869502
TI  - Influence of endophytic Bacillus pumilus and EDTA on the phytoextraction of Cu
      from soil by using Cicer arietinum.
AB  - In developing countries, soil contamination with metals is ubiquitous, which
      poses a serious threat to the ecosystem. The current study was designed to screen
      out the nested belongings of Cicer arietinum plants and Bacillus pumilus (KF
      875447) in extracting copper (Cu) from contaminated soils. A pot experiment was
      executed by growing C. arietinum seedlings either inoculated with B. pumilus or
      uninoculated along with the application of 5 mM ethylenediaminetetraacetic acid
      (EDTA). Plants were subjected to three different concentrations of Cu (250, 350,
      and 500 ppm) for 48 days. An increase in Cu uptake was observed in C. arietinum
      plants inoculated with B. pumilus as compared to uninoculated ones. C. arietinum
      exhibited improved values for different growth parameters in the presence of B.
      pumilus, that is, root length (37%), shoot length (31%), whole plant fresh as
      well as (45%) dry weight (27%), and chlorophyll contents (32%). More than 70% of
      tolerance index (TI) was observed for plants at 500 ppm Cu treatment. Addition of
      B. pumilus and EDTA significantly increased metal uptake by C. arietinum up to 19
      and 36%, respectively, while the application of B. pumilus and EDTA in
      combination increased metal accumulation by 41%. The calculated bioaccumulation
      and translocation factor (TF) revealed that C. arietinum possess phytoextraction
      potential for Cu, and this ability is significantly improved with application of
      B. pumilus and EDTA amendments.

PMID- 27869503
TI  - Social health and dementia: a European consensus on the operationalization of the
      concept and directions for research and practice.
AB  - BACKGROUND: Because the pattern of illnesses changes in an aging population and
      many people manage to live well with chronic diseases, a group of health care
      professionals recently proposed reformulating the static WHO definition of health
      towards a dynamic one based on the ability to physically, mentally and socially
      adapt and self-manage. This paper is the result of a collaborative action of the
      INTERDEM Social Health Taskforce to operationalize this new health concept for
      people with dementia, more specifically the social domain, and to formulate
      directions for research and practice to promote social health in dementia.
      METHOD: Based on the expertise of the Social Health Taskforce members (N = 54)
      three groups were formed that worked on operationalizing the three social health
      dimensions described by Huber et al.: (1) capacity to fulfil potential and
      obligations; (2) ability to manage life with some degree of independence; (3)
      participation in social activities. For each dimension also influencing factors,
      effective interventions and knowledge gaps were inventoried. After a consensus
      meeting, the operationalizations of the dimensions were reviewed by the European
      Working Group of People with Dementia (EWGPWD). RESULTS: The social health
      dimensions could be well operationalized for people with dementia and are
      assessed as very relevant according to the Social Health Taskforce and EWGPWD.
      Personal (e.g. sense of coherence, competencies), disease-related (e.g. severity
      of cognitive impairments, comorbidity), social (support from network, stigma) and
      environmental factors (e.g. enabling design, accessibility) that can influence
      the person with dementia's social health and many interventions promoting social
      health were identified. CONCLUSION: A consensus-based operationalization of
      social health in dementia is proposed, and factors that can influence, and
      interventions that improve, social health in dementia identified. Recommendations
      are made for research and practice.

PMID- 27869504
TI  - Initial Content Validation Results of a New Simulation Model for Flexible
      Ureteroscopy: The Key-Box.
AB  - PURPOSE: We sought to test the content validity of a new training model for
      flexible ureteroscopy: the Key-Box. MATERIAL AND METHODS: Sixteen medical
      students were randomized to undergo a 10-day training consisting of performing 10
      different exercises aimed at learning specific movements with the flexible
      ureteroscope, and how to catch and release stones with a nitinol basket using the
      Key-Box (n = 8 students in the training group, n = 8 students in the nontraining
      control group). Subsequently, an expert endourologist (O.T.) blindly assessed
      skills acquired by the whole cohort of students through two exercises on
      ureteroscope manipulation and one exercise on stone capture selected among those
      used for the training. A performance scale (1-5) assessing different steps of the
      procedure was used to evaluate each student. Time to complete the exercises was
      measured. Mann-Whitney Rank Sum test was used for comparisons between the two
      groups. RESULTS: Mean scores obtained by trained students were significantly
      higher compared with those obtained by nontrained students (all p < 0.001). All
      trained students were able to complete the two exercises on ureteroscope
      manipulation within 3 minutes, whereas two students (25%) were not able to finish
      the exercise on stone capture. Conversely, four (50%) and six (75%) nontrained
      students were not able to finish one out of the two exercises on ureteroscope
      manipulation and the exercise on stone capture, respectively. The mean time to
      complete the three exercises was 76.3, 69.9, and 107 and 172.5, 137.9, and 168
      seconds in the trained and nontrained groups, respectively (all p < 0.001).
      CONCLUSIONS: The K-Box(r) seems to be a valid easy-to-use training model for
      initiating novel endoscopists to flexible ureteroscopy.

PMID- 27869505
TI  - Using Propensity Scores to Examine the Association Between Behavioral
      Inhibition/Activation and Nonsuicidal and Suicidal Self-Injury.
AB  - BACKGROUND: Self-injurious behavior (e.g., nonsuicidal self-injury, suicide
      attempts) is a serious public health concern. One potentially important but
      understudied predictor of nonsuicidal and suicidal self-injury involves the
      behavioral inhibition and activation system (BIS/BAS). AIMS: The goal of the
      current study was to examine the relationship between nonsuicidal and suicidal
      self-injury and BIS/BAS, and to consider the influence of related variables in
      the relationship. Examination through this framework allowed us to consider BIS
      and BAS as potential unique risk factors of self-injury. METHOD: After examining
      the relationship between nonsuicidal and suicidal self-injury and BIS/BAS among
      1,912 participants, we used propensity scores to match participants' propensity
      for nonsuicidal self-injury and suicide attempts based on demographic variables
      (e.g., gender, age) and related risk factors (e.g., anxiety, depressive
      symptomology, impulsivity, and substance use problems). RESULTS: Participants who
      reported nonsuicidal self-injury or attempted suicide scored higher on BIS and
      BAS compared with those without a history of these behaviors. After matching
      procedures, however, the only group difference found was on BIS between those
      with and without a history of nonsuicidal self-injury. CONCLUSION: Results
      support the notion that the behavioral inhibition system might play a role in
      nonsuicidal self-injury but not in suicidal self-injury.

PMID- 27869506
TI  - Testing a Model of Functional Impairment in Telephone Crisis Support Workers.
AB  - BACKGROUND: It is well known that helping professionals experience functional
      impairment related to elevated symptoms of psychological distress as a result of
      frequent empathic engagement with distressed others. Whether telephone crisis
      support workers are impacted in a similar way is not currently reported in the
      literature. AIMS: The purpose of this study was to test a hypothesized model of
      factors contributing to functional impairment in telephone crisis support
      workers. METHOD: A national sample of 210 telephone crisis support workers
      completed an online survey including measures of emotion regulation, symptoms of
      general psychological distress and suicidal ideation, intentions to seek help for
      symptoms, and functional impairment. Structural equation modeling was used to
      test the fit of the data to the hypothesized model. RESULTS: Goodness-of-fit
      indices were adequate and supported the interactive effects of emotion
      regulation, general psychological distress, suicidal ideation, and intentions to
      seek help for ideation on functional impairment. CONCLUSION: These results
      warrant the deliberate management of telephone crisis support workers' impairment
      through service selection, training, supervision, and professional development
      strategies. Future research replicating and extending this model will further
      inform the modification and/or development of strategies to optimize telephone
      crisis support workers' well-being and delivery of support to callers.

PMID- 27869507
TI  - Parent-Child Connectedness and Long-Term Risk for Suicidal Ideation in a
      Nationally Representative Sample of US Adolescents.
AB  - BACKGROUND: Few studies have addressed on the role of parent-child connectedness
      (PCC) on adolescents' risk for suicidal ideation from a longitudinal,
      developmental perspective. AIM: This study examined PCC during adolescence and
      risk of suicidal ideation into adulthood among a nationally representative sample
      of American adolescents. METHOD: The study includes 13,234 adolescents aged 11-18
      from the National Longitudinal Study of Adolescent to Adult Health (Add Health)
      who were surveyed during adolescence (1994-1995) and then again in early
      adulthood (2008-2009). Multinomial logistic regression estimated the association
      between PCC during adolescence and having ideation during the adolescence period
      only, in adulthood only, and in both adolescence and adulthood as compared with
      those without suicidal ideation. RESULTS: After adjusting for depressive symptoms
      and other parent and adolescent characteristics, adolescents in two-parent
      households who reported higher PCC during adolescence had lower relative risk of
      having ideation during adolescence alone and in both adolescence and adulthood.
      In mother-only households, higher mother connectedness was also associated with
      decreased risk of having adolescent ideation. CONCLUSION: PCC is an important
      modifiable target for the prevention of suicidal ideation from adolescence into
      adulthood.

PMID- 27869508
TI  - Risk Factors and Mediators of Suicidal Ideation Among Korean Adolescents.
AB  - BACKGROUND: A significant number of Korean adolescents have suicidal ideations
      and it is more prevalent among adolescents than any other age group in Korea.
      AIMS: This study was conducted to attain a better understanding of the
      contributing factors to suicidal ideation among Korean adolescents. METHOD: We
      recruited 569 high school students in Grades 10 and 11 in Pyeongtaek, Korea. The
      Beck Scale for Suicidal Ideation was used to measure suicidal ideation as the
      outcome variable. The Interpersonal Needs Questionnaire, the Beck Hopelessness
      Scale, the School Related Stress Scale, the Olweus Bully/Victim Questionnaire,
      and the Youth Risk Behavior Surveillance questions were used to measure thwarted
      belongingness and perceived burdensomeness, hopelessness, school-related stress,
      bullying, and previous suicidal behaviors, respectively. Data analyses included
      descriptive statistics and structural equation modeling. RESULTS: The findings
      suggest that perceived burdensomeness, hopelessness, school-related stress, and
      previous suicidal behaviors have significant direct effects on suicidal ideation.
      Hopelessness fully mediated the relation between thwarted belongingness and
      suicidal ideation, and partially mediated between perceived burdensomeness,
      school-related stress, and suicidal ideation. CONCLUSION: These findings provide
      more specific directions for a multidimensional suicide prevention program in
      order to be successful in reducing suicide rates among Korean adolescents.

PMID- 27869509
TI  - Encapsulated benzoic acid supplementation in broiler diets influences gut
      bacterial composition and activity.
AB  - 1. The present study investigated the effects of encapsulated benzoic acid (BA)
      supplementation in broiler feed on performance and gastrointestinal microbiota.
      2. Eighty broilers were randomly divided into two groups. Birds in the control
      group were fed on maize-soybean-based diets. Birds in the treatment group were
      provided the same diet supplemented with 2 g/kg BA encapsulated in a vegetable
      oil matrix. 3. At the end of the trial (d 35), pH, bacterial composition and
      metabolites were determined in the crop, jejunum, ileum and caecum. 4. Growth
      performance variables and pH were not significantly different. 5. BA
      concentration decreased rapidly in the proximal gut. However, the treatment diet
      showed higher BA in the crop, jejunum, ileum and caecum. 6. Total lactate in the
      crop and D-lactate in the jejunum was higher in the BA treated group. Caecal
      total and branched chain fatty acids were decreased due to the treatment. 7.
      Lactobacilli populations were significantly altered by BA supplementation. A
      trend for increased lactobacilli was observed in the crop, while it became
      significant in the jejunum and ileum. Lactobacillus species responded differently
      to the treatment. Four of 5 measured Lactobacillus species, particularly in the
      ileum, followed the course observed for total lactobacilli; only Lactobacillus
      salivarius was not modified. 8. Correlation analysis showed that BA modified the
      intestinal microbiota. Lactobacilli correlated negatively to all studied
      clostridial clusters and enterobacteria. Clostridial clusters IV and XIVa were
      significantly increased in the jejunum, whereas only clostridial cluster XIVa was
      increased in the caecum. 9. Encapsulated BA modified the intestinal microbiota
      which can lead to the conclusion, that the main beneficial mode of action of BA
      in the gut appears to be the enhancement of lactic acid bacteria, which in turn
      may act as a vanguard against pathogens.

PMID- 27869510
TI  - The effectiveness of commercial desiccants and uncooked rice in removing moisture
      from hearing aids.
AB  - OBJECTIVE: In many low- and middle-income countries, the availability of hearing
      technology is limited, with few options for hearing aid repairs. Minimising
      moisture damage to hearing aid electronics improves function and longevity;
      however, desiccants that absorb moisture from hearing aid components are
      unavailable in many regions. This study compared the effectiveness of uncooked
      white rice and seven commercial silica gel desiccants in removing moisture from
      hearing aids. DESIGN: Relative humidity measurements in a test chamber were
      obtained from a water-saturated BTE hearing aid prior to and after placement in
      uncooked white rice and seven different silica gel desiccants. STUDY SAMPLE: Two
      BTE hearing aids, seven silica gel desiccants and white rice comprised the study
      sample. RESULTS: All desiccants and the white rice were effective in removing
      moisture from hearing aids, with Hal Hen Super Dri Aid showing the largest mean
      reduction in relative humidity. Based on analysis of covariance results, white
      rice was statistically similar to several of the commercial desiccants.
      CONCLUSIONS: White rice shows promise as an effective alternative to commercial
      desiccants in reducing moisture in hearing aids when silica gel products are
      unavailable. As this study was conducted in a relatively dry region, additional
      research may be needed.

PMID- 27869511
TI  - Acoustic reflexes are common but not pervasive: evidence from the National Health
      and Nutrition Examination Survey, 1999-2012.
AB  - OBJECTIVE: To determine whether acoustic reflexes are pervasive (i.e.
      sufficiently prevalent to provide 95% confidence of at least 95% prevalence) and
      might be invoked in damage-risk criteria (DRC) and health hazard assessments
      (HHA) for impulsive noise. DESIGN: Cross-sectional analyses of a nationally
      representative study. STUDY SAMPLE: National Health and Nutrition Examination
      Survey (NHANES) data collected between 1999 and 2012 were used. Over 60 thousand
      reflex traces obtained from 15,106 NHANES participants were used in the study,
      along with demographic, audiometric, health and exposure variables obtained in
      that study. RESULTS: Acoustic reflexes were not sufficiently prevalent to be
      deemed pervasive by any detection method or in any subgroup defined by age or
      audiometric characteristics. The odds of observing acoustic reflexes were greater
      for women, young adults, and people with better hearing sensitivity. Abnormally
      high tympanometric admittance and "Other" race/ethnicity (i.e. people who do not
      self-identify as exclusively Non-Hispanic White, Non-Hispanic Black, Mexican
      American, or Hispanic) were associated with lower odds. CONCLUSIONS: Acoustic
      reflexes are not sufficiently prevalent to be included in DRC and HHA for
      impulsive noise.

PMID- 27869512
TI  - Controversies in the management of cancer-associated thrombosis.
AB  - INTRODUCTION: Cancer associated thrombosis (CAT) is a frequent complication among
      cancer patients. It is associated with increased morbidity, mortality, and
      psychological burden. Areas covered: Low-molecular-weight heparin monotherapy for
      the initial 6 months is considered the standard of care for the acute and long
      term management of CAT. For patients at high risk of recurrent CAT (e.g. active
      cancer or still undergoing anticancer therapy) beyond the initial 6 months of
      treatment, continuation of anticoagulation therapy for secondary prevention is
      usually recommended. The management of anticoagulation therapy is more
      challenging in patients with cancer. Cancer patients are more likely to have
      recurrent events despite anticoagulation, thrombocytopenia due to their
      chemotherapy regimens or have incidental pulmonary embolism diagnosed on their
      staging imaging. Expert commentary: We will review expert consensuses and
      opinions in order to guide clinicians on how to tailor the management of CAT in
      these special circumstances.

PMID- 27869513
TI  - Adverse effects of pesticides on central auditory functions in tobacco growers.
AB  - OBJECTIVE: To investigate the effects of exposure to pesticides on the central
      auditory functions (CAF) of Brazilian tobacco growers. DESIGN: This was a cross
      sectional study carried out between 2010 and 2012. Participants were evaluated
      with two behavioural procedures to investigate CAF, the random gap detection test
      (RGDT) and the dichotic digit test in Portuguese (DDT). STUDY SAMPLE: A total of
      22 growers exposed to pesticides (study group) and 21 subjects who were not
      exposed to pesticides (control group) were selected. RESULTS: No significant
      differences between groups were observed for pure-tone thresholds. A significant
      association between pesticide exposure and the results for RGDT and DDT was
      found. Significant differences between pesticide-exposed and nonexposed subjects
      were found for RGDT frequency average and DDT binaural average, when including
      age and hearing level as covariates. Age was significantly associated with RGDT
      frequency average, DDT left ear score, DDT binaural average and DDT right ear
      advantage. Hearing levels were not significantly associated with any of the test
      scores. The relative risk of failing the DDT and RGDT for the study group was
      1.88 (95% CI: 1.10-3.20) and 1.74 (95% CI: 1.06-2.86), respectively, as compared
      with the control group. CONCLUSIONS: The results showed that tobacco growers
      exposed to pesticides exhibited signs of central auditory dysfunction
      characterised by decrements in temporal processing and binaural integration
      processes/abilities.

PMID- 27869515
TI  - Vi capsular polysaccharide: Synthesis, virulence, and application.
AB  - Vi capsular polysaccharide, a linear homopolymer of alpha-1,4-linked N
      acetylgalactosaminuronate, is characteristically produced by Salmonella enterica
      serovar Typhi. The Vi capsule covers the surface of the producing bacteria and
      serves as an virulence factor via inhibition of complement-mediated killing and
      promoting resistance against phagocytosis. Furthermore, Vi also represents a
      predominant protective antigen and plays a key role in the development of
      vaccines against typhoid fever. Herein, we reviewed the latest advances
      associated with the Vi polysaccharide, from its synthesis and transport within
      bacterial cells, mechanisms involved in virulence, immunological characteristics,
      and applications in vaccine, as well as its purification and detection methods.

PMID- 27869516
TI  - Frequency and clinical implications of SOX11 expression in Burkitt lymphoma.

PMID- 27869517
TI  - CT fluoroscopy-guided percutaneous drainage: comparison of the one step and the
      Seldinger techniques.
AB  - OBJECTIVE: To evaluate the one step technique compared with the Seldinger
      technique in computed tomography (CT) fluoroscopy-guided percutaneous drainage of
      abdominal and pelvic abscess. MATERIAL AND METHODS: Seventy-six consecutive
      patients (49 men, 27 women; mean age 63.5 years, range 19-87 years) with
      abdominal and pelvic abscess were included in this study. Drainages were
      performed with the one step (n = 46) and with the Seldinger (n = 48) technique
      between September 2012 and June 2014. RESULTS: The technical success and clinical
      success rates were 95.8% and 93.5%, respectively, for the one step group, and
      97.8% and 95.7%, respectively, for the Seldinger group. The mean procedure time
      was significantly shorter with the one step than with the Seldinger method (15.0
      +/- 4.3 min, range 10-29 min vs. 21.0 +/- 9.5 min, range 13-54 min, p < .01). The
      mean abscess size and depth were 73.4 +/- 44.0 mm and 42.5 +/- 19.3 mm,
      respectively, in the one step group, and 61.0 +/- 22.8 mm and 35.0 +/- 20.7 mm in
      the Seldinger group. CONCLUSION: The one step technique was easier and faster
      than the Seldinger technique. The effectiveness of both techniques was similar
      for the CT fluoroscopy-guided percutaneous drainage of abdominal and pelvic
      abscess.

PMID- 27869518
TI  - Gender differences in identifying emotions from auditory and visual stimuli.
AB  - The present study focused on gender differences in emotion identification from
      auditory and visual stimuli produced by two male and two female actors.
      Differences in emotion identification from nonsense samples, language samples and
      prolonged vowels were investigated. It was also studied whether auditory stimuli
      can convey the emotional content of speech without visual stimuli, and whether
      visual stimuli can convey the emotional content of speech without auditory
      stimuli. The aim was to get a better knowledge of vocal attributes and a more
      holistic understanding of the nonverbal communication of emotion. Females tended
      to be more accurate in emotion identification than males. Voice quality
      parameters played a role in emotion identification in both genders. The emotional
      content of the samples was best conveyed by nonsense sentences, better than by
      prolonged vowels or shared native language of the speakers and participants.
      Thus, vocal non-verbal communication tends to affect the interpretation of
      emotion even in the absence of language. The emotional stimuli were better
      recognized from visual stimuli than auditory stimuli by both genders. Visual
      information about speech may not be connected to the language; instead, it may be
      based on the human ability to understand the kinetic movements in speech
      production more readily than the characteristics of the acoustic cues.

PMID- 27869519
TI  - A post-planktonic era of in vitro infectious models: issues and changes addressed
      by a clinically relevant wound like media.
AB  - Medical science is pitted against an ever-increasing rise in antibiotic tolerant
      microorganisms. Concurrently, during the past decade, biofilms have garnered much
      attention within research and clinical practice. Although the significance of
      clinical biofilms is becoming very apparent, current methods for diagnostics and
      direction of therapy plans in many hospitals do not reflect this knowledge; with
      many of the present tools proving to be inadequate for accurately mimicking the
      biofilm phenomenon. Based on current findings, we address some of the fundamental
      issues overlooked by clinical labs: the paradigm shifts that need to occur in
      assessing chronic wounds; better simulation of physiological conditions in vitro;
      and the importance of incorporating polymicrobial populations into biofilm
      models. In addition, this review considers using a biofilm relevant in vitro
      model for cultivating and determining the antibiotic tolerance and susceptibility
      of microorganisms associated with chronic wounds. This model presents itself as a
      highly rapid and functional tool that can be utilized by hospitals in an aim to
      improve bedside treatments.

PMID- 27869521
TI  - Body and spirit: Tibetan medical paintings.

PMID- 27869520
TI  - Outpatient single-port laparoscopic percutaneous Morgagni hernia repair assisted
      by an optical forceps.
AB  - Morgagni hernia is a relatively rare form of diaphragmatic hernia in the
      pediatric age group and it is conventionally treated with open surgical repair.
      Minimal access surgery is currently being adapted for many procedures in
      children. However, to date just a few techniques have been described relevant to
      minimal access surgical repair of Morgagni hernia in children. Herein, we report
      two cases of Morgagni hernia repaired by a new single-port laparoscopic technique
      assisted by an optical forceps. Two infants, a one-year-old boy and an eight
      month-old girl, were operated with this technique in just 26 and 35 min and were
      discharged with oral analgesic prescription by postoperative hour 5 and 8,
      respectively. In the English-language literature, these cases are the first
      reports of laparoscopic Morgagni hernia repair that were performed as an
      outpatient procedure. Also, the technique introduced can be easily applied by a
      single surgeon without an assistant to operate the laparoscope.

PMID- 27869522
TI  - Current aspects of Salmonella contamination in the US poultry production chain
      and the potential application of risk strategies in understanding emerging
      hazards.
AB  - One of the leading causes of foodborne illness in poultry products is Salmonella
      enterica. Salmonella hazards in poultry may be estimated and possible control
      methods modeled and evaluated through the use of quantitative microbiological
      risk assessment (QMRA) models and tools. From farm to table, there are many
      possible routes of Salmonella dissemination and contamination in poultry. From
      the time chicks are hatched through growth, transportation, processing, storage,
      preparation, and finally consumption, the product could be contaminated through
      exposure to different materials and sources. Examination of each step of the
      process is necessary as well as an examination of the overall picture to create
      effective countermeasures against contamination and prevent disease. QMRA
      simulation models can use either point estimates or probability distributions to
      examine variables such as Salmonella concentrations at retail or at any given
      point of processing to gain insight on the chance of illness due to Salmonella
      ingestion. For modeling Salmonella risk in poultry, it is important to look at
      variables such as Salmonella transfer and cross contamination during processing.
      QMRA results may be useful for the identification and control of critical sources
      of Salmonella contamination.

PMID- 27869524
TI  - Altered expression pattern of SLAM family receptors on pathological B cells of
      patients with chronic lymphocytic leukemia.

PMID- 27869523
TI  - Nelarabine in the treatment of pediatric and adult patients with T-cell acute
      lymphoblastic leukemia and lymphoma.
AB  - INTRODUCTION: T-cell acute lymphoblastic leukemia (ALL) and lymphoma (LBL) are
      aggressive hematologic neoplasms that are treated with combination chemotherapy
      in the frontline, but have limited options in the relapsed or refractory setting.
      Based on observations in patients with purine nucleoside phosphorylase (PNP)
      deficiency, a guanosine nucleoside analogue, arabinosylguanine (ara-G) was
      developed that provided T-cell specificity. Nelarabine was developed as the water
      soluble, clinically useful-prodrug of ara-G and based on its activity was
      approved for the treatment of relapsed or refractory T-ALL/LBL. Areas covered: In
      this narrative review, we will summarize the preclinical studies, early dose
      finding studies, and efficacy studies that led to approval of nelarabine. The
      review will succinctly cover response rates and safety signals reported during
      clinical development. We will also cover more recent work with nelarabine,
      including combination studies, modified dosing schedules, and frontline treatment
      approaches. Expert commentary: Based on evidence from the literature review and
      our own experience with nelarabine, we conclude that it is an effective agent in
      the treatment of T-cell malignancies. Understanding the factors that modulate the
      risk of dose-limiting neurotoxicity, how to mitigate this toxicity, and how to
      safely combine it with other active agents will continue to broaden its use.

PMID- 27869526
TI  - PGC-1alpha over-expression suppresses the skeletal muscle atrophy and myofiber
      type composition during hindlimb unloading.
AB  - Disuse leads to severe muscle atrophy and a slow-to-fast myofiber-type
      transition. PGC-1alpha (Peroxisome proliferator-activated receptor gamma
      coactivator 1alpha) is documented to play an important role in muscle atrophy and
      slow-twitch myofiber determination. Transcription of atrophy-related Atrogin-1 by
      FoxO3 can be reduced by PGC-1alpha. While Smad3 augments FoxO3-induced Atrogin-1
      and MuRF1 promoter activity. So PGC-1alpha, as a transcription co-activator, may
      regulate hindlimb unloading (HU)-induced myofiber-type transition and muscle
      atrophy through Smad3. Our results showed that transgenic PGC-1alpha mice
      resisted HU-induced muscle loss, atrophy-related genes expression, and slow-to
      fast myofiber-type transition. Furthermore, over-expression of PGC-1alpha
      resisted the increase in pSmad3 during muscle atrophy in vivo and in vitro. And,
      PGC-1alpha over-expression inhibited the expression of atrogenes via suppressing
      the phosphorylation of Smad3 in vitro. Thus, PGC-1alpha is effective in
      regulating myofiber-type transition during HU, and it alleviates skeletal muscle
      atrophy partially through suppressing the activation of Smad3.

PMID- 27869525
TI  - Oxidative Priority, Meal Frequency, and the Energy Economy of Food and Activity:
      Implications for Longevity, Obesity, and Cardiometabolic Disease.
AB  - In most modern societies, the relationship that many individuals have with food
      has fundamentally changed from previous generations. People have shifted away
      from viewing food as primarily sustenance, and rather now seek out foods based on
      pure palatability or specific nutrition. However, it is far from clear what
      optimal nutrition is for the general population or specific individuals. We
      previously described the Food Triangle as a way to organize food based on an
      increasing energy density paradigm, and now expand on this model to predict the
      impact of oxidative priority and both nutrient and fiber density in relation to
      caloric load. When combined with meal frequency, integrated energy expenditure,
      macronutrient oxidative priority, and fuel partitioning expressed by the
      respiratory quotient, our model also offers a novel explanation for chronic
      overnutrition and the cause of excess body fat accumulation. Herein, we not only
      review how metabolism is a dynamic process subject to many regulators that
      mediate the fate of ingested calories but also discuss how the Food Triangle
      predicts the oxidative priority of ingested foods and provides a conceptual
      paradigm for healthy eating supported by health and longevity research.

PMID- 27869527
TI  - Impact of touring, performance schedule, and definitions on 1-year injury rates
      in a modern dance company.
AB  - There is ongoing debate about how to define injury in dance: the most
      encompassing one or a time-loss definition. We examined the relationship between
      touring, performance schedule and injury definition on injury rates in a
      professional modern dance company over one-year. In-house healthcare management
      tracked 35 dancers for work-related musculoskeletal injuries (WMSI), time-loss
      injuries (TLinj), complaints, and exposure. The year was divided into 6 segments
      to allow comparison of effects of performance, rehearsal, and touring.
      Injuries/segment were converted into injuries/1000-h dance exposure. We conducted
      negative binomial regression analysis to determine differences between segments,
      P <= 0.05. Twenty WMSI, 0.44 injuries/1000-h, were sustained over one-year. WMSI
      were 6 times more likely to occur in Segment-6, compared with other segments
      (incident rate ratio = 6.055, P = 0.031). The highest rate of TLinj and traumatic
      injuries also occurred in Segment-6, reflecting concentrated rehearsal, New York
      season and performances abroad. More overuse injuries occurred in Segment-2, an
      international tour, attributed to raked stages. Lack of methods to quantify
      performance other than injury may mask effects of touring on dancer's well-being.
      Tracking complaints permits understanding of stressors to specific body regions
      and healthcare utilisation; however, TLinj remain the most important injuries to
      track because they impact other dancers and organisational costs.

PMID- 27869529
TI  - Low fundamental movement skill proficiency is associated with high BMI and body
      fatness in girls but not boys aged 6-11 years old.
AB  - This study examined differences in children's body mass index (BMI) and body
      fatness (BF%) as a function of gender and fundamental movement skill (FMS)
      proficiency. Following ethics approval and parental consent, 248, 6-11 year-old
      children (112 boys, 136 girls) underwent assessment of 7 FMS: sprint run, side
      gallop, hop, kick, catch, throw and vertical jump. FMS tertiles ("high", "medium"
      or "low" FMS) were created based on the summed components of the FMS. Skinfold
      measures were used to calculate BF%. Physical activity (PA) was assessed using
      pedometry and maturation predicted using anthropometry. Data were analysed using
      a 2 (Gender) * 3 (FMS tertile) ways analysis of covariance (ANCOVA), controlling
      for age, maturation and PA. Age (P = .001) and maturation (P = .006) were
      associated with BMI. Girls classified as high FMS proficiency had significantly
      lower BMI compared to girls with low and medium FMS proficiency. Age (P = .0001)
      and maturation (P = .007) were associated with BF%. BF% was also higher for girls
      with low FMS compared to those with medium and high FMS. BF% and BMI were not
      different across FMS tertile in boys. Such findings suggest focusing on FMS may
      be especially important for healthy weight, particularly in girls.

PMID- 27869530
TI  - Composing alarms: considering the musical aspects of auditory alarm design.
AB  - Short melodies are commonly linked to referents in jingles, ringtones, movie
      themes, and even auditory displays (i.e., sounds used in human-computer
      interactions). While melody associations can be quite effective, auditory alarms
      in medical devices are generally poorly learned and highly confused. Here, we
      draw on approaches and stimuli from both music cognition (melody recognition) and
      human factors (alarm design) to analyze the patterns of confusions in a paired
      associate alarm-learning task involving both a standardized melodic alarm set
      (Experiment 1) and a set of novel melodies (Experiment 2). Although contour
      played a role in confusions (consistent with previous research), we observed
      several cases where melodies with similar contours were rarely confused -
      melodies holding musically distinctive features. This exploratory work suggests
      that salient features formed by an alarm's melodic structure (such as repeated
      notes, distinct contours, and easily recognizable intervals) can increase the
      likelihood of correct alarm identification. We conclude that the use of musical
      principles and features may help future efforts to improve the design of auditory
      alarms.

PMID- 27869528
TI  - The Association Between Measures of Fitness and Metabolic Health in Treatment
      Seeking Youth with Obesity.
AB  - BACKGROUND: Both cardiorespiratory fitness (CRF) and measures of muscular fitness
      are associated with metabolic syndrome in adults. However, limited information
      exists about these relationships in youth with severe obesity who are at
      increased risk of metabolic dysfunction. The purpose of this study was to examine
      the relationship between fitness and metabolic health in treatment-seeking youth
      with obesity. METHODS: Data for this analysis were collected at the time of
      baseline visits at a stage 3 pediatric weight management center. Maximal
      voluntary contractions were obtained by using isometric hand-grip dynamometry,
      and CRF was obtained from a maximal treadmill test. Resting blood pressure and
      fasting measures of blood lipids, glucose, and insulin were used to calculate a
      continuous metabolic syndrome score (cMetS); homeostasis model assessment of
      insulin resistance (HOMA-IR) was calculated from fasting insulin and glucose.
      Relationships between measures of fitness and metabolic health were evaluated by
      using partial correlations adjusted for age. RESULTS: Sixty-nine participants (21
      boys, 48 girls) were included in this analysis. Of these, 46% (n = 32) met the
      criteria for metabolic syndrome. No differences were found between boys and girls
      for any variable analyzed. Muscular strength was positively associated with cMetS
      (r = 0.35), though this association weakened after adjustment for body mass index
      percentile. CRF was inversely associated with homeostasis model assessment of
      insulin resistance (HOMA-IR) (r = -0.26) and fasting insulin (r = -0.27). Body
      fat percentage was positively associated with insulin (r = 0.36). No significant
      relationship was found between CRF and cMetS. CONCLUSION: Contrary to previous
      studies, CRF was not associated with metabolic syndrome in this group. Muscular
      strength, however, was associated with cMetS. Notably, CRF was associated with
      elevated HOMA-IR, which may be seen as a precursor to metabolic syndrome. These
      results suggest that CRF and muscular strength influence metabolic function
      independently.

PMID- 27869531
TI  - Associations Between Lifestyle Characteristics and the Presence of Nonalcoholic
      Fatty Liver Disease: A Case-Control Study.
AB  - BACKGROUND: Dietary and physical activity (PA) habits have been suggested as
      important factors for nonalcoholic fatty liver disease (NAFLD). Published data
      are mainly focused on the effect of either diet or exercise, whereas data on
      other aspects like sleep remain sparse. The aim of this study was to explore
      potential associations between dietary intake, PA, and sleeping habits, and the
      presence of NAFLD. METHODS: One hundred patients with ultrasound-proven NAFLD and
      55 healthy controls matched for age, sex, and body mass index were included.
      Dietary habits were assessed through a semiquantitative validated food frequency
      questionnaire. PA level was assessed with a validated questionnaire. Total night
      sleep hours and duration of midday rest were also recorded. Optimal sleep
      duration was defined as sleep hours >=7 and <=9 hr/day. RESULTS: Patients
      compared to controls consumed less vegetables and nuts, more sweets, drank less
      coffee and alcohol (all P < 0.05), and exhibited a lower level of PA (P = 0.006).
      PA level [odds ratio (OR) per 100 metabolic equivalent of task-min/day = 0.74,
      95% confidence interval (CI) 0.61-0.89, P = 0.002] was associated with lower
      probability of having NAFLD, whereas sweets consumption (OR = 2.13, 95% CI 1.22
      3.71, P = 0.008) was associated with increased probability, after adjusting for
      several confounders, including body weight status. Optimal sleep duration was
      marginally and inversely associated with NAFLD presence (OR = 0.38, 95% CI 0.14
      1.01, P = 0.05). CONCLUSION: Higher PA level and optimal sleep duration are
      associated with lower likelihood, whereas sweets consumption is associated with
      higher likelihood of having NAFLD. These associations are independent of body
      weight status and energy intake.

PMID- 27869533
TI  - Commentary on Some Recent Theses Relevant to Combating Aging: December 2016.

PMID- 27869532
TI  - Molecular Characterization of Methicillin-Resistant Staphylococcus aureus from
      Outpatients in Northern Japan: Increasing Tendency of ST5/ST764 MRSA-IIa with
      Arginine Catabolic Mobile Element.
AB  - Arginine catabolic mobile element (ACME) is a genomic island of staphylococcus
      and is considered to confer enhanced ability to survive and growth on host
      bacterial cells. ACME has been typically identified in Panton-Valentine
      Leukocidin (PVL)-positive ST8 methicillin-resistant Staphylococcus aureus (MRSA)
      with SCCmec type IVa (USA300 clone), and it is also found in other lineages at
      low frequency. Prevalence and molecular characteristics of PVL+and/or ACME+ MRSA
      were investigated for 624 clinical isolates collected from outpatients in
      northern Japan from 2013 to 2014. Both PVL genes and ACME type I were detected in
      nine isolates (1.4%), which were ST8-MRSA-SCCmec IVa/spa type t008/agr-I; whereas
      solely PVL genes were positive in two isolates, ST30-MRSA-SCCmec IV and ST59-MRSA
      SCCmec V. ACME type II' (previously referred to as ACME DeltaII) was detected in
      36 isolates (5.8%) with SCCmec II and V (32 and 4 isolates, respectively),
      exhibiting an increased rate within SCCmec II-MRSA (7.1%) compared with our
      previous studies (0.86-4.5%, 2008-2011). ACME II'-positive MRSA strains were
      classified into ST5-SCCmec IIa/V or ST764-SCCmec IIa belonging to five different
      spa types, with t002 being dominant. They harbored mostly enterotoxin gene
      clusters (seg-sei-sem-sen-seo-seu) and some more enterotoxin genes (seb1, seb2,
      sec3, sel, sep), showing resistance to more antimicrobials than ST8-MRSA-SCCmec
      IVa. ACME-SCCmec composite island (CI) of the 36 ACME II'-positive MRSA was
      classified into five types (ii)-(vi), among which type (ii) (orfX-PsiSCCDeltaJ1
      SCCmec I-ACME II'-SCCmec II) was dominant and subdivided into the A3 variant and
      the less common A2 variant. CI types (v) and (vi) were considered novel genetic
      organizations having speG (acetyltransferase genes for polyamines) in inserted
      SCC4610/SCC266-like genetic elements. The present study revealed increased
      prevalence and genetic diversity of the ST5/ST764-MRSA-SCCmec II with ACME II' in
      northern Japan.

PMID- 27869534
TI  - Training to Improve Walking after Pediatric Spinal Cord Injury: A Systematic
      Review of Parameters and Walking Outcomes.
AB  - Walking or locomotor training is often initiated following pediatric spinal cord
      injury (SCI). There is no synthesis of the literature on interventions targeting
      walking for pediatric SCI, although this would assist future clinical trials and
      interventions. To address this need, we completed a systematic review to
      summarize the who, what, when, and how of walking interventions in children with
      SCI. Participant characteristics, training parameters, and walking outcomes with
      training in pediatric SCI were identified and compared with training parameters
      and outcomes in adults with SCI. The PubMed, Medline, AMED, Embase, PsycInfo,
      Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic
      Reviews, and CINAHL databases were searched for studies that included
      participants aged 1-17 years with a SCI acquired post-birth, physical
      interventions, and pre- and post-training walking measures. Two researchers
      evaluated each study's risk of bias using a domain-based approach. Training
      parameters and walking outcomes were extracted. Total training duration (duration
      * frequency * number of weeks) was calculated. Thirteen pediatric studies (n = 43
      children) were included; all but one were case series/reports. Risk of bias was
      high in the pediatric studies. A 2012 adult review was updated (11 studies
      added). As with adults, the training durations, frequencies, and modes used with
      the children varied; however, overground walking practice was included in 10/13
      pediatric studies. Improvements in walking capacity, speed, and distance were
      comparable between children and adults. There was a trend for greater gains with
      greater total training durations. There is a paucity of high-quality research
      examining interventions targeting walking after pediatric SCI; however, intensive
      training, including practice overground, results in notable improvements.

PMID- 27869535
TI  - Serum Thyroid-Stimulating Hormone Levels and Frailty in the Elderly: The Progetto
      Veneto Anziani Study.
AB  - High or low thyroid-stimulating hormone (TSH) levels seem to be associated with
      several negative outcomes in the elderly, but the literature about TSH and
      frailty is still limited. In this article, we investigated whether TSH is
      associated with prevalent and incident frailty in a cohort of older community
      dwelling subjects. Among 3099 initially screened in the Progetto Veneto Anziani
      Study, 2571 men and women aged >=65 years (for cross-sectional analyses) and 1732
      (longitudinal, mean follow-up period of 4.4 years) were divided into sex-specific
      quintiles according to baseline serum TSH concentrations within normal range (0.3
      and 4.2 mUI/L). Frailty was defined as the presence of three among five Fried's
      criteria. At baseline, taking those in the third quintile of serum TSH as
      reference (Q3) and adjusting for potential confounders, participants in the
      highest (Q5) quintile had an increased odds ratio (OR) of having frailty (OR =
      1.55; 95% confidence interval [CI]: 1.03-2.33 for men; OR = 1.97; 95% CI: 1.59
      2.45 for women). Men in Q1 had significant higher odds of having muscle weakness
      and exhaustion, while those in Q5 had muscle weakness and slow gait speed. Women
      in Q1 had significantly higher odds of having all the Fried's criteria (except
      for exhaustion), while those in Q5 reported a significantly higher presence of
      muscle weakness and slow gait speed. At follow-up, men in Q5 had an increased
      risk of frailty (OR = 1.37; 95% CI: 1.02-1.91) similar to women in Q1 (OR = 1.47;
      95% CI: 1.21-1.78). In conclusion, men with higher and women with lower serum TSH
      levels are at increased risk of frailty.

PMID- 27869536
TI  - Comparative analysis of nonvolatile and volatile metabolites in Lichtheimia
      ramosa cultivated in different growth media.
AB  - Lichtheimia ramosa is one of the predominant filamentous fungi in Korean
      traditional nuruk. The nonvolatile and volatile metabolites of L. ramosa
      cultivated in three growth media: complete medium (CM), potato dextrose broth
      (PDB), and sabouraud dextrose broth (SDB), were investigated and compared. Among
      nonvolatile metabolites, serine, lysine, and ornithine increased in CM and PDB
      cultivated with L. ramosa during the exponential phase. In addition, glucose
      level increased in CM whereas decreased in PDB and SDB. The major volatile
      metabolites in the extract samples were acetic acid, ethanol, 3-methyl-2-buten-1
      ol, 2-phenylethanol, ethylacetate, 2-furaldehyde, 5-(hydroxymethyl)-2
      furaldehyde, 2,3-dihydro-3,5,-dihydroxy-6-methyl-4H-pyran-4-one, and alpha
      humulene. In particular, the levels of volatile metabolites related to makgeolli
      (e.g., acetic acid, ethanol, and ethyl acetate) were highest in extracts
      cultivated in CM. On the other hand, the level of 2-phenylethanol was relatively
      higher in PDB and SDB, possibly due to there being more phenylalanine present in
      the biomass sample in media.

PMID- 27869539
TI  - ?

PMID- 27869538
TI  - Stigma receptivity over the lifetime of the hermaphroditic flower of Elsholtzia
      rugulosa was negatively correlated with pollen viability.
AB  - Dichogamy is generally thought to be a mechanism that prevents self-fertilization
      in flowering plants. This study aims to investigate the relationships between
      floral age and stigma receptivity, style length and pollen viability, and define
      how floral characters avoid self-pollination in a gynodioecious Chinese plant,
      Elsholtzia rugulosa. We assessed the relationships between flower age and style
      length, stigma receptivity, and pollen viability in E. rugulosa. This species
      produces 2 forms with plants bearing either hermaphrodite flowers (H) or female
      flowers (F). Corolla length in F flowers was shorter than the corolla length of H
      flowers and produced no pollen. H flowers were protandrous, pollen release of H
      flowers occurred before stigma receptivity. Stigma receptivity was significantly
      positively correlated with style length in both F flowers and H flowers. Pollen
      viability in H flowers declined significantly with floral age. Our results
      suggest that self-pollination in H flowers is likely reduced by dichogamy because
      stigma receptivity and pollen viability were effectively separated in time.
      However, because H inflorescences typically have multiple flowers open at the
      same time means that geitonogamous selfing is not avoided.

PMID- 27869540
TI  - The Brief Cognitive Impairment Scale (BCIS): preliminary investigation of a
      severe-stage dementia test emphasizing cognitive processing and interpersonal
      tolerance.
AB  - We describe the development and validation of The Brief Cognitive Impairment
      Scale (BCIS), a cognitive screening instrument designed for persons with severe
      stage dementia. Psychometric analyses were performed on neuropsychological data
      from long-term care residents (N = 247) who completed a brief battery of tests,
      including the BCIS. A principle component analysis yielded three factors that
      provide insight into how persons with severe dementia cognitively process
      information and may tolerate specific aspects of social stimulation, such as
      during personal care. A BCIS cut score can be used to identify severe dementia
      with a sensitivity of .82, a specificity of .84, and an area under the curve of
      .89. It may be used by clinicians or caregivers when advanced dementia is
      suspected, as an alternative to measures with suspected floor effects, when
      residents cannot tolerate more demanding assessment tools, and as part of non
      pharmacologic treatment plans for behavior disturbances associated with dementia.

PMID- 27869541
TI  - Callosal disconnection neglect: reassessment after 34 years.
AB  - In 1984, Watson and Heilman reported a patient with a partial callosal
      disconnection following an infarction of the anterior portion of her corpus
      callosum. This woman's performance on line-bisection tasks revealed "callosal
      disconnection neglect." The objective of this research is to reexamine this woman
      34 years after her callosal disconnection to gain information about her recovery.
      The patient completed visual line-bisection tasks in which horizontal lines were
      placed in the right, left, and center hemispaces and she performed these
      bisections using her right or left hand. Unlike her performance 34 years ago in
      which each hand deviated to its ipsilateral hemispace, with greater deviation
      when lines were placed in the contralateral rather than ipsilateral hemispace,
      currently, there were no significant main effects for hand or spatial position.
      Thus, there were notable differences between this woman's most recent performance
      on the line bisection and her previous performance 34 years ago. Unlike her prior
      testing 34 years back, this woman's most recent performance resembled the
      performance of a previous tested healthy control group for whom differences in
      hand and hemispace were not found. It remains unclear whether her callosal
      disconnection neglect improved because each hemisphere learned to allocate
      ipsilateral spatial attention or because she learned a compensatory strategy in
      which she turned her body so that the lines placed in her right or left hemispace
      were now toward her midline.

PMID- 27869537
TI  - RNA binding to APOBEC deaminases; Not simply a substrate for C to U editing.
AB  - Apolipoprotein B mRNA Editing Catalytic Polypeptide-like 1 or APOBEC1 was
      discovered in 1993 as the zinc-dependent cytidine deaminase responsible for the
      production of an in frame stop codon in apoB mRNA through modification of
      cytidine at nucleotide position 6666 to uridine. At the time of this discovery
      there was much speculation concerning the mechanism of base modification RNA
      editing which has been rekindled by the discovery of multiple C to U RNA editing
      events in the 3' UTRs of mRNAs and the finding that other members of the APOBEC
      family while able to bind RNA, have the biological function of being DNA mutating
      enzymes. Current research is addressing the mechanism for these nucleotide
      modification events that appear not to adhere to the mooring sequence-dependent
      model for APOBEC1 involving the assembly of a multi protein containing editosome.
      This review will summarize our current understanding of the structure and
      function of APOBEC proteins and examine how RNA binding to them may be a
      regulatory mechanism.

PMID- 27869542
TI  - Treatment challenge of a cyanobacterium Romeria elegans bloom in a South
      Australian wastewater treatment plant - a case study.
AB  - A bloom of the non-toxic cyanobacterium Romeria elegans in waste stabilisation
      ponds (WSPs) within Angaston waste water treatment plant (WWTP) has posed an
      unprecedented treatment challenge for the local water utility. The water from the
      WSPs is chlorinated for safety prior to reuse on nearby farmland. Cyanobacteria
      concentrations of approximately 1.2 * 106 cells mL-1 increased the chlorine
      demand dramatically. Operators continuously increased the disinfectant dose up to
      50 mg L-1 to achieve operational guideline values for combined chlorine (0.5-1.0
      mg L-1) prior to reuse. Despite this, attempts to achieve targeted combined
      chlorine residual (CCR) failed. In this study, samples from the waste
      stabilisation pond at Angaston WWTP were chlorinated over a range of doses.
      Combined chlorine, disinfection by-product formation, cyanobacteria cell
      concentration, Escherichia coli inactivation, as well as dissolved organic carbon
      and free ammonia were monitored. This study shows that, in the occurrence of
      cyanobacterial blooms, CCR does not directly suggest pathogen removal efficiency
      and is therefore not an ideal parameter to evaluate the effectiveness of
      disinfection process in WWTP. Instead, E. coli removal is a more direct and
      practical parameter for the determination of the efficiency of the disinfection
      process.

PMID- 27869543
TI  - Direct Bonding of Chitosan Biomaterials to Tissues Using Transglutaminase for
      Surgical Repair or Device Implantation.
AB  - Natural biomaterials, such as chitosan and collagen, are useful for biomedical
      applications because they are biocompatible, mechanically robust, and
      biodegradable, but it is difficult to rapidly and tightly bond them to living
      tissues. In this study, we demonstrate that the microbial transglutaminase (mTG),
      can be used to rapidly (<5 min) bond chitosan and collagen biomaterials to the
      surfaces of hepatic, cardiac, and dermal tissues, as well as to functionalized
      polydimethylsiloxane (PDMS) materials that are used in medical products. The mTG
      bonded chitosan patches effectively sealed intestinal perforations, and a newly
      developed two-component mTG-bonded chitosan spray effectively repaired ruptures
      in a breathing lung when tested ex vivo. The mechanical strength of mTG-catalyzed
      chitosan adhesive bonds were comparable to those generated by commonly used
      surgical glues. These results suggest that mTG preparations may be broadly
      employed to bond various types of organic materials, including polysaccharides,
      proteins, and functionalized inorganic polymers to living tissues, which may open
      new avenues for biomedical engineering, medical device integration, and tissue
      repair.

PMID- 27869544
TI  - Cloning and expression analysis of a novel tissue-specific dopa decarboxylase
      mRNA splicing variant in Bombyx mori.
AB  - Dopa decarboxylase (DDC) protein is involved in the synthesis of dopamine and
      serotonin. Here, we show that in the silkworm Bombyx mori, a novel DDC splicing
      variant is selectively expressed in the brain and subesophageal ganglia. In
      Drosophila melanogaster, a neuron-specific isoform of DDC is known to be
      alternatively spliced in a similar manner.

PMID- 27869545
TI  - Noninvasive Monitoring of Three-Dimensional Chondrogenic Constructs Using
      Molecular Beacon Nanosensors.
AB  - Chondrogenic differentiation of human mesenchymal stem cells (MSCs) in three
      dimensional hydrogel holds promise as a method for repairing injured articular
      cartilage. Given MSC plasticity (its potential to mature into alternative
      lineages), nondestructive monitoring is critical for the optimization of
      chondrogenic differentiation conditions and the evaluation of the final product.
      However, conventional validation/assessments of the differentiation process
      (i.e., quantitative reverse transcription polymerase chain reaction [qRT-PCR] and
      histology) are end-point assays requiring disruption of the sample. This report
      introduces molecular beacon (MB)-based nanosensors to achieve noninvasive
      monitoring of chondrogenic differentiation. These nanosensors consist of
      biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs)
      encapsulating MBs to detect Type II Collagen (Col2) and glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) mRNAs that serve as lineage-specific and
      housekeeping biomarkers, respectively. The sustainable release of MBs from MB-NPs
      allows longitudinal monitoring of MSCs undergoing chondrogenic differentiation
      over a period of 28 days. Dual-colored MB loading ensures accurate assessment of
      Col2 mRNA expression level, where potential heterogeneity in nanosensor uptake
      and retention by MSCs are taken into account. When normalized nanosensor signal
      was compared against qRT-PCR result, a tight correlation was observed (R2 =
      0.9301). Finally, nanosensor usage was compatible with MSC potency with minimal
      influence on chondrogenic, adipogenic, and osteogenic differentiation.

PMID- 27869546
TI  - Models for nearly every occasion: Part I - One box models.
AB  - The standard "well mixed room," "one box" model cannot be used to predict
      occupational exposures whenever the scenario involves the use of local controls.
      New "constant emission" one box models are proposed that permit either local
      exhaust or local exhaust with filtered return, coupled with general room
      ventilation or the recirculation of a portion of the general room exhaust. New
      "two box" models are presented in Part II of this series. Both steady state and
      transient models were developed. The steady state equation for each model,
      including the standard one box steady state model, is augmented with an
      additional factor reflecting the fraction of time the substance was generated
      during each task. This addition allows the easy calculation of the average
      exposure for cyclic and irregular emission patterns, provided the starting and
      ending concentrations are zero or near zero, or the cumulative time across all
      tasks is long (e.g., several tasks to a full shift). The new models introduce
      additional variables, such as the efficiency of the local exhaust to immediately
      capture freshly generated contaminant and the filtration efficiency whenever
      filtered exhaust is returned to the workspace. Many of the model variables are
      knowable (e.g., room volume and ventilation rate). A structured procedure for
      calibrating a model to a work scenario is introduced that can be applied to both
      continuous and cyclic processes. The "calibration" procedure generates estimates
      of the generation rate and all of remaining unknown model variables.

PMID- 27869547
TI  - Dynamic Risk Stratification for Predicting Recurrence in Patients with
      Differentiated Thyroid Cancer Treated Without Radioactive Iodine Remnant Ablation
      Therapy.
AB  - BACKGROUND: Increased incidence of small differentiated thyroid cancer (DTC) has
      emphasized the need for risk stratification and individualized disease management
      for these low risk DTCs. The aim of this study was to validate a new dynamic risk
      stratification (DRS) system for the prediction of structural recurrent/persistent
      disease in patients with DTC treated without radioactive iodine (RAI) remnant
      ablation therapy. METHODS: This historical cohort study included 357 patients
      with DTC treated with lobectomy or total thyroidectomy without RAI therapy. We
      stratified patient response to initial treatment as excellent, indeterminate,
      biochemical incomplete, and structural incomplete according to the DRS system.
      RESULTS: During a median follow-up of 8.6 years, 3.6% patients had structural
      recurrent DTC. The response was excellent in 71.7% patients, indeterminate in
      18.5%, biochemical incomplete in 8.4%, and structural incomplete in 1.4%. There
      were significant differences in DFS among the DRS groups (p < 0.001). The hazard
      ratio (HR) of recurrent/persistent disease was significantly higher in the
      biochemical incomplete group (HR = 20.8, p < 0.001) and structural incomplete
      group (HR = 243.3, p < 0.001) compared with the excellent group. However, the
      Tumor Node Metastasis staging system and the American Thyroid Association initial
      risk classification did not effectively predict recurrence of DTC. CONCLUSIONS:
      The new DRS system was effective for predicting risk of recurrent/persistent
      disease in patients with DTC who underwent lobectomy or total thyroidectomy
      without RAI remnant ablation.

PMID- 27869548
TI  - Evaluation of a sprinkler cooling system on inhalable dust and ammonia
      concentrations in broiler chicken production.
AB  - Workers are exposed to dust in broiler chicken production during daily work
      activities. Poultry dust may contain inflammatory agents (e.g., endotoxin) and
      inhalation exposure has been associated with pulmonary symptoms. Current practice
      to reduce worker exposure to poultry dust is the use of respiratory protection
      (e.g., elastomeric face-piece respirator with a P100 and ammonia chemical
      cartridge). Limited research has been conducted to evaluate engineering controls
      to reduce dust and ammonia concentrations in broiler chicken production;
      therefore, the purpose of this research was to evaluate the effectiveness of a
      water sprinkling system to reduce inhalable dust and ammonia concentrations in a
      broiler chicken house. Inhalable dust and ammonia concentrations were measured
      daily for the production cycle of a flock of broiler chickens (63 days).
      Inhalable dust was measured gravimetrically using an inhalable sampler and
      ammonia was measured by a direct reading sensor. Sampling was performed on a
      stationary mannequin inside two broiler chicken houses. One house used a
      sprinkler cooling system to deliver a water mist throughout the house and the
      second house was an untreated control. The sprinkler system activated after day 5
      of chicken placement, releasing water periodically from 6 am to 10 pm. The amount
      of sprinkling increased at day 10 and day 15 as recommended by the manufacturer.
      Geometric mean (GM) inhalable dust concentrations measured in the treatment house
      (5.5 mg/m3) were not different (p = 0.33) than those found in the control house
      (6.0 mg/m3). The GM ammonia concentrations were also not different (p = 0.34)
      across the treatment and control house [10.6 ppm (GSD: 1.80); GM 9.51 ppm (GSD:
      1.77)], respectively. The use of cost effective engineering, administrative and
      personal exposure controls are needed in the poultry industry to effectively
      reduce worker's exposure to hazardous concentrations of dust and ammonia.

PMID- 27869549
TI  - Carotid artery stenting with double cerebral embolic protection in asymptomatic
      patients - a diffusion-weighted MRI controlled study.
AB  - BACKGROUND: The aim of this study was to compare the simultaneous double
      protection method (proximal balloon plus distal filter) with distal-filter
      protection or proximal-balloon protection alone in asymptomatic patients during
      carotid artery stenting. PATIENTS AND METHODS: 119 consecutive patients were
      investigated for carotid artery stentings in the extracranial internal carotid
      artery with the use of distal filters (n = 41, 34.4 %), proximal balloon (MoMa)
      protection (n = 40, 33.6 %) or double protection (n = 38, 31.9 %). Magnetic
      resonance imaging (MRI) was performed on all patients before the procedure, and
      control diffusion-weighted MRI (DW-MRI) was obtained within 24-48 h after the
      procedure. Procedural data, complications, success rate, major adverse
      cardiovascular events, and MRI findings were collected. RESULTS: New cerebral
      high-intensity (HI) lesions were observed in 47 (39.4 %) patients. HI lesions
      were observed in 22 (53.6 %), 15 (37.5 %), and 10 (26.3 %) of the patients with
      distal filters, proximal protection, and double protection, respectively (p =
      0.004). The average number of HI lesions on DW-MRI was 1.80 in the distal-filter
      group, 0.90 in the proximal-balloon group, and 0.55 in the double-protection
      group (p < 0.001). Procedure and fluoroscopy times were slightly longer in the
      double-protection group compared to the distal- or proximal-protection groups (p
      = 0.001). CONCLUSIONS: The double (proximal plus distal) cerebral embolic
      protection technique is safe and effective for minimizing the risk of cerebral
      embolization, even in patients with asymptomatic carotid artery stenosis, despite
      slightly longer procedure and fluoroscopy times.?.

PMID- 27869550
TI  - Models for nearly every occasion: Part II - Two box models.
AB  - The "well-mixed room" two box models are often used to predict near and far field
      concentrations for a specific task, but are limited to scenarios where local
      exhaust controls are not used. In Part II of this series, new two box models are
      presented that permit local controls that either exhaust to the outside or return
      filtered air to the workspace. Additional models are presented that also allow
      for the recirculation of a filtered portion of the general ventilation flowrate.
      During the concentration increase phase the emission rate is assumed to be
      relatively constant. Both steady state and transient equations were developed for
      each scenario. An additional factor, representing the fraction of time that the
      substance is being emitted during a task or set of tasks, was added to the
      standard and new steady state models. This simple modification permits the easy
      calculation of the average near and far field concentrations for cyclic and
      irregular emission patterns, provided the starting and ending concentrations are
      identical (e.g., zero or near zero) or the cumulative task time is long (e.g.,
      two or more task cycles to a full shift, depending upon the number of room air
      changes per task). Additional variables are introduced with the new models, such
      as the efficiency of a local control to immediately capture freshly generated
      contaminant and the filtration efficiency whenever filtered exhaust is returned
      to the workspace. Many of the model variables are knowable (e.g., room volume and
      ventilation rate). Others can be approximated using manufacturer specifications
      or published values (e.g., filtration efficiency). A structured procedure for
      calibrating a model to a work scenario is presented that can be applied to both
      continuous and cyclic processes. The "calibration" procedure generates estimates
      of all of the unknown model variables, including the generation rate and the
      effective near field flowrate (which takes into account potentially complex near
      field air currents as well as any thermal plumes created by a hot process).

PMID- 27869551
TI  - Critical limb ischaemia and the response to bone marrow-derived cell therapy
      according to tcPO2 measurement.
AB  - BACKGROUND: Cell therapy is an emerging potential biotherapy for critical limb
      ischaemia (CLI) patients who are not eligible for revascularization. However, the
      findings on this technique's efficacy are inconsistent. Trials investigating this
      topic focused on the more severe CLI patients who were often beyond any therapy.
      Therefore, identifying those who may truly benefit from cell transplantation is
      now warranted. To this end, we studied the prognostic value of tcPO2 for major
      amputation after 1 year in patients treated with bone marrow-derived cells.
      PATIENTS AND METHODS: CLI patients ineligible for revascularization were included
      in a cell-therapy pilot study. On inclusion, patients underwent tcPO2 measurement
      in supine and sitting positions. For a tcPO2 < 10 mmHg in the supine position,
      the vascular reserve was defined by tcPO2 > 30 mmHg in the sitting position.
      Patients were administered intramuscular injections of mononuclear cells derived
      from aspirated bone marrow. RESULTS: In total, 25 patients (a lower limbs) were
      included for analysis. At inclusion, 11 lower limbs had tcPO2 at rest > 10 mmHg,
      and 16 lower limbs had a tcPO2 < 10 mmHg. The success probability for cell
      therapy was 0.79 (95 % CI 0.38-0.94) and 0.44 (95 % CI 0.18-0.67), respectively
      (p = 0.1). Of the 16 limbs with tcPO2 < 10 mmHg, the success rate was
      considerably higher in patients demonstrating a tcPO2 increase in a sitting
      position of over 30 mmHg (6/8, success probability 0.71, 95 % CI 0.26-0.92)
      compared to those without (2/8, success probability 0.15, 95 % CI 0.01-0.48, p =
      0.03). CONCLUSIONS: For patients with chronic CLI for whom cellular therapy is a
      therapeutic option, a tcPO2 < 10 mmHg at rest, without vascular reserve (i. e. <
      30 mmHg when sitting), is a prognostic indicator for poor outcome.?.

PMID- 27869552
TI  - Validation of a method for sedatives and beta-blockers determination in swine,
      bovine and equine kidney using liquid chromatography coupled with tandem mass
      spectrometry.
AB  - A method for the determination of five sedatives and 14 beta-blocker residues in
      swine, bovine and equine kidney was validated. Samples were extracted with
      acetonitrile and purified using dispersive solid phase extraction (d-SPE) with
      Celite 545 with subsequent analysis by LC-MS/MS. A simplified protocol was
      applied to validate the method scope extension to include new matrices.
      Parameters such as recovery, trueness, linearity (r2), relative standard
      deviation (RSD), decision limit (CCalpha) and method capability (CCbeta) were
      measured for the bovine and equine kidney matrices. The method was applied to the
      analysis of more than 300 real samples and is currently included in the Brazilian
      National Residue Control Plan.

PMID- 27869553
TI  - Radiation-Induced Chemical Reactions in Hydrogel of Hydroxypropyl Cellulose
      (HPC): A Pulse Radiolysis Study.
AB  - We performed studies on pulse radiolysis of highly transparent and shape-stable
      hydrogels of hydroxypropyl cellulose (HPC) that were prepared using a radiation
      crosslinking technique. Several fundamental aspects of radiation-induced chemical
      reactions in the hydrogels were investigated. With radiation doses less than 1
      kGy, degradation of the HPC matrix was not observed. The rate constants of the
      HPC composing the matrix, with two water decomposition radicals [hydroxyl radical
      (*OH) and hydrated electron ([Formula: see text])] in the gels, were determined
      to be 4.5 * 109 and 1.8 * 107 M-1 s-1, respectively. Direct ionization of HPC in
      the matrix slightly increased the initial yield of [Formula: see text], but the
      additionally produced amount of [Formula: see text] disappeared immediately
      within 200 ps, indicating fast recombination of [Formula: see text] with hole
      radicals on HPC or on surrounding hydration water molecules. Reactions of
      [Formula: see text] with nitrous oxide (N2O) and nitromethane (CH3NO2) were also
      examined. Decay of [Formula: see text] due to scavenging by N2O and CH3NO2 were
      both slower in hydrogels than in aqueous solutions, showing slower diffusions of
      the reactants in the gel matrix. The degree of decrease in the decay rate was
      more effective for N2O than for CH3NO2, revealing lower solubility of N2O in gel
      than in water. It is known that in viscous solvents, such as ethylene glycol,
      CH3NO2 exhibits a transient effect, which is a fast reaction over the contact
      distance of reactants and occurs without diffusions of reactants. However, such
      an effect was not observed in the hydrogel used in the current study. In
      addition, the initial yield of [Formula: see text], which is affected by the
      amount of the scavenged precursor of [Formula: see text], in hydrogel containing
      N2O was slightly higher than that in water containing N2O, and the same tendency
      was found for CH3NO2.

PMID- 27869554
TI  - Genome-Wide Deletion Screening with the Array CGH Method in Mouse Offspring
      Derived from Irradiated Spermatogonia Indicates that Mutagenic Responses are
      Highly Variable among Genes.
AB  - Until the end of the 20th century, mouse germ cell data on induced mutation
      rates, which were collected using classical genetic methods at preselected
      specific loci, provided the principal basis for estimates of genetic risks from
      radiation in humans. The work reported on here is an extension of earlier efforts
      in this area using molecular methods. It focuses on validating the use of array
      comparative genomic hybridization (array CGH) methods for identifying radiation
      induced copy number variants (CNVs) and specifically for DNA deletions. The
      emphasis on deletions stems from the view that it constitutes the predominant
      type of radiation-induced genetic damage, which is relevant for estimating
      genetic risks in humans. In the current study, deletion mutations were screened
      in the genomes of F1 mice born to unirradiated or 4 Gy irradiated sires at the
      spermatogonia stage (100 offspring each). The array CGH analysis was performed
      using a "2M array" with over 2 million probes with a mean interprobe distance of
      approximately 1 kb. The results provide evidence of five molecularly-confirmed
      paternally-derived deletions in the irradiated group (5/100) and one in the
      controls (1/100). These data support a calculation, which estimates that the
      mutation rate is 1 * 10-2/Gy per genome for induced deletions; this is much lower
      than would be expected if one assumes that the specific locus rate of 1 * 10
      5/locus per Gy (at 34 loci) is applicable to other genes in the genome. The low
      observed rate of induced deletions suggests that the effective number of
      genes/genomic regions at which recoverable deletions could be induced would be
      only approximately 1,000. This estimate is far lower than expected from the size
      of the mouse genome (>20,000 genes). Such a discrepancy between observation and
      expectation can occur if the genome contains numerous genes that are far less
      sensitive to radiation-induced deletions, if many deletion-bearing offspring are
      not viable or if the current method is substandard for detecting small deletions.

PMID- 27869555
TI  - The Influence of the CTIP Polymorphism, Q418P, on Homologous Recombination and
      Predisposition to Radiation-Induced Tumorigenesis (mainly rAML) in Mice.
AB  - Exposure to ionizing radiation increases the incidence of acute myeloid leukemia
      (AML), which has been diagnosed in Japanese atomic bombing survivors, as well as
      patients treated with radiotherapy. The genetic basis for susceptibility to
      radiation-induced AML is not well characterized. We previously identified a
      candidate murine gene for susceptibility to radiation-induced AML (rAML): C
      terminal binding protein (CTBP)-interacting protein (CTIP)/retinoblastoma binding
      protein 8 (RBBP8). This gene is essential for embryonic development, double
      strand break (DSB) resection in homologous recombination (HR) and tumor
      suppression. In the 129S2/SvHsd mouse strain, a nonsynonymous single nucleotide
      polymorphism (nsSNP) in Ctip, Q418P, has been identified. We investigated the
      role of Q418P in radiation-induced carcinogenesis and its effect on CTIP function
      in HR. After whole-body exposure to 3 Gy of X rays, 11 out of 113 (9.7%)
      129S2/SvHsd mice developed rAML. Furthermore, 129S2/SvHsd mouse embryonic
      fibroblasts (MEFs) showed lower levels of recruitment of HR factors, Rad51 and
      replication protein A (RPA) to radiation-induced foci, compared to CBA/H and
      C57BL/6 MEFs, isolated from rAML-sensitive and resistant strains, respectively.
      Mitomycin C and alpha particles induced lower levels of sister chromatid
      exchanges in 129S2/SvHsd cells compared to CBA/H and C57BL/6. Our data
      demonstrate that Q418P nsSNP influences the efficiency of CTIP function in HR
      repair of DNA DSBs in vitro and in vivo, and appears to affect susceptibility to
      rAML.

PMID- 27869557
TI  - Extreme Positions in Sport Science and the Importance of Context: It Depends?

PMID- 27869556
TI  - Evaluation of On- and Off-Line Bioluminescence Tomography System for Focal
      Irradiation Guidance.
AB  - In response to the limitations of computed tomography (CT) and cone-beam CT
      (CBCT) in irradiation guidance, especially for soft-tissue targets without the
      use of contrast agents, our group developed a solution that implemented
      bioluminescence tomography (BLT) as the image-guidance modality for preclinical
      radiation research. However, adding such a system to existing small animal
      irradiators is no small task. A potential solution is to utilize an off-line BLT
      system in close proximity to the irradiator, with stable and effective animal
      transport between the two systems. In this study, we investigated the
      localization accuracy of an off-line BLT system when used for the small animal
      radiation research platform (SARRP) and compared the results with those of an on
      line system. The CBCT was equipped on both the off-line BLT system and the SARRP,
      with a distance of 5 m between them. To evaluate the setup error during animal
      transport between the two systems, the mice underwent CBCT imaging on the SARRP
      and were then transported to the off-line system for a second CBCT imaging
      session. The normalized intensity difference of the two images and the
      corresponding histogram and correlation were computed to evaluate if the
      transport process perturbed animal positioning. Strong correlation (correlation
      coefficients >0.95) between the SARRP and the off-line mouse CBCT was observed.
      The offset of the implanted light source center can be maintained within 0.2 mm
      during transport. To compare the target localization accuracy using the on-line
      SARRP BLT and the off-line system, a self-illuminated bioluminescent source was
      implanted in the abdomen of anesthetized mice. In addition to the application for
      dose calculation, CBCT imaging was also employed to generate the mesh grid of the
      imaged mouse for BLT reconstruction. Two scenarios were devised and compared,
      which involved localization of the luminescence source based on either: 1. on
      line SARRP bioluminescence image and CBCT; or 2. off-line bioluminescence image
      and SARRP CBCT. The first scenario is assumed to have the least setup error,
      because no animal transport was involved. The second scenario examines if an off
      line BLT system, with the mesh generated from the SARRP CBCT, can be used to
      guide SARRP irradiation when there is minimal target contrast in CBCT. Stability
      during animal transport between the two systems was maintained. The center of
      mass (CoM) of the light source reconstructed by the off-line BLT had an offset of
      1.0 +/- 0.4 mm from the true CoM derived from the SARRP CBCT. These results are
      comparable to the offset of 1.0 +/- 0.2 mm using on-line BLT. With CBCT
      information provided by the SARRP and effective animal immobilization during
      transport, these findings support the utilization of an off-line BLT-guided
      system, in close proximity to the SARRP, for accurate soft-tissue target
      localization. In addition, a dedicated standalone BLT system for our partner site
      at the University of Pennsylvania was introduced in this study.

PMID- 27869559
TI  - Two-Way Regularized Fuzzy Clustering of Multiple Correspondence Analysis.
AB  - Multiple correspondence analysis (MCA) is a useful tool for investigating the
      interrelationships among dummy-coded categorical variables. MCA has been combined
      with clustering methods to examine whether there exist heterogeneous subclusters
      of a population, which exhibit cluster-level heterogeneity. These combined
      approaches aim to classify either observations only (one-way clustering of MCA)
      or both observations and variable categories (two-way clustering of MCA). The
      latter approach is favored because its solutions are easier to interpret by
      providing explicitly which subgroup of observations is associated with which
      subset of variable categories. Nonetheless, the two-way approach has been built
      on hard classification that assumes observations and/or variable categories to
      belong to only one cluster. To relax this assumption, we propose two-way fuzzy
      clustering of MCA. Specifically, we combine MCA with fuzzy k-means simultaneously
      to classify a subgroup of observations and a subset of variable categories into a
      common cluster, while allowing both observations and variable categories to
      belong partially to multiple clusters. Importantly, we adopt regularized fuzzy k
      means, thereby enabling us to decide the degree of fuzziness in cluster
      memberships automatically. We evaluate the performance of the proposed approach
      through the analysis of simulated and real data, in comparison with existing two
      way clustering approaches.

PMID- 27869560
TI  - Syncope, seizure or both?
AB  - Ictal asystole (IA) is a rare phenomenon in patients with seizures with an
      incidence of 0.27-0.4% and has been proposed as a possible mechanism of sudden
      unexpected death in epilepsy patients (SUDEP). We present a case of a 53-year-old
      woman who initially presented with episodes of expressive aphasia and was treated
      with antiepileptic drugs (AEDs). While on therapy she experienced episodes of
      syncope. During her hospitalization for tapering of AEDs and 24-hour EEG
      monitoring, the patient developed a seizure followed by sinus bradycardia and an
      18-second sinus pause, resulting in loss of consciousness and slowing of cerebral
      activity. Ten seconds after the return of cardiac activity, the EEG showed return
      of cerebral activity. A dual chamber pacemaker was implanted.

PMID- 27869558
TI  - Polynitroxylated Pegylated Hemoglobin-A Novel, Small Volume Therapeutic for
      Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response
      Evaluation.
AB  - Resuscitation with polynitroxylated pegylated hemoglobin (PNPH), a pegylated
      bovine hemoglobin decorated with nitroxides, eliminated the need for fluid
      administration, reduced intracranial pressure (ICP) and brain edema, and produced
      neuroprotection in vitro and in vivo versus Lactated Ringer's solution (LR) in
      experimental traumatic brain injury (TBI) plus hemorrhagic shock (HS). We
      hypothesized that resuscitation with PNPH would improve acute physiology versus
      whole blood after TBI+HS and would be safe and effective across a wide dosage
      range. Anesthetized mice underwent controlled cortical impact and severe HS to
      mean arterial pressure (MAP) of 25-27 mm Hg for 35 min, then were resuscitated
      with PNPH, autologous whole blood, or LR. Markers of acute physiology, including
      mean arterial blood pressure (MAP), heart rate (HR), blood gases/chemistries, and
      brain oxygenation (PbtO2), were monitored for 90 min on room air followed by 15
      min on 100% oxygen. In a second experiment, the protocol was repeated, except
      mice were resuscitated with PNPH with doses between 2 and 100 mL/kg. ICP and 24 h
      %-brain water were evaluated. PNPH-resuscitated mice had higher MAP and lower HR
      post-resuscitation versus blood or LR (p < 0.01). PNPH-resuscitated mice, versus
      those resuscitated with blood or LR, also had higher pH and lower serum potassium
      (p < 0.05). Blood-resuscitated mice, however, had higher PbtO2 versus those
      resuscitated with LR and PNPH, although PNPH had higher PbtO2 versus LR (p <
      0.05). PNPH was well tolerated across the dosing range and dramatically reduced
      fluid requirements in all doses-even 2 or 5 mL/kg (p < 0.001). ICP was
      significantly lower in PNPH-treated mice for most doses tested versus in LR
      treated mice, although %-brain water did not differ between groups. Resuscitation
      with PNPH, versus resuscitation with LR or blood, improved MAP, HR, and ICP,
      reduced acidosis and hyperkalemia, and was well tolerated and effective across a
      wide dosing range, supporting ongoing pre-clinical development of PNPH for TBI
      resuscitation.

PMID- 27869562
TI  - Wanting to Be Seen: Young People's Experiences of Performative Making Out.
AB  - People engage in sexual behavior for many reasons, some of which require an
      audience (e.g., arousing onlookers, making someone jealous). In this study, we
      investigated the prevalence, motivations, and outcomes of young people's
      experiences with performative making out-making out with someone and wanting
      others to see. Of the 155 female and 194 male college students who completed the
      online questionnaire, 32% of the women and 37% of the men reported having done
      this, often before entering college. Significantly more women than men reported
      same-sex performative experiences. We used thematic analysis to identify themes
      in the qualitative data. Participants' motivations included enhancing their
      image, causing jealousy or envy, demonstrating a relationship, sexually arousing
      men, and participating in fun and games. Men reported that their reputations were
      enhanced more often than damaged; women reported the opposite pattern. These
      results provide insights into the functions of sexual behavior as a means of
      communication and highlight gender differences consistent with problematic
      cultural belief systems such as "slut shaming," victim blaming, and sexual double
      standards.

PMID- 27869561
TI  - Successful drug-coated balloon angioplasty and single anti-platelet therapy to
      treat an ischaemic stroke patient with haemorrhage and acute coronary syndrome.
AB  - A 55-year-old male presented with two challenging problems, i.e. acute coronary
      syndrome (ACS) and a major bleeding episode. He first presented with ischaemic
      stroke and was treated with thrombolysis. However this was complicated by
      haemorrhagic transformation. He subsequently developed ACS with urgent coronary
      angiography demonstrating a critical stenosis in the proximal left anterior
      descending artery. Percutaneous coronary intervention (PCI) was deemed necessary
      but we were mindful of causing bleeding complications from the use of anti
      thrombotic therapy. Despite the complexities, we used a novel approach in terms
      of PCI strategy and anti-platelet regimen (drug-coated balloon angioplasty and a
      single anti-platelet therapy) and achieved a successful outcome.

PMID- 27869564
TI  - Willingness to Engage in Consensual Nonmonogamy Among Emerging Adults: A
      Structural Equation Analysis of Sexual Identity, Casual Sex Attitudes, and
      Gender.
AB  - Research on consensual nonmonogamy (CNM) has increased over the past decade.
      However, willingness to engage in CNM is an understudied phenomenon within this
      body of literature. Little research has examined the correlates of this aspect of
      CNM or focused on individuals in the developmental period of emerging adulthood.
      This study used multigroup structural equation modeling (SEM) to test a
      conceptual model of emerging adults' (ages 18 to 29; N = 890) willingness to
      engage in CNM. Results indicated that emerging adult
      experimentation/possibilities, sexual identity exploration, and permissive
      attitudes toward casual sex were all related to willingness to engage in CNM.
      Results also showed that the pathway from emerging adult
      experimentation/possibilities to willingness to engage in CNM was differentially
      mediated across gender. Specifically, for women there was an indirect (and
      positive) pathway from experimentation/possibilities to willingness to engage in
      CNM through sexual identity exploration. For men there was an indirect (and
      positive) pathway from experimentation/possibilities to willingness to engage in
      CNM through permissive attitudes toward casual sex. Implications for future
      studies on CNM among emerging adults are discussed.

PMID- 27869563
TI  - Subjective Report of Side Effects of Prescribed and Nonprescribed Psychostimulant
      Use in Young Adults.
AB  - BACKGROUND: Side effects of prescribed and nonprescribed psychostimulant use are
      understudied. OBJECTIVES: The study examined side effects of prescribed and
      nonprescribed psychostimulant use in a college sample with attention to possible
      gender differences. METHODS: 2716 undergraduates (1448 male) between the ages of
      17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that
      included questions about the subjective side effects of prescribed and
      nonprescribed psychostimulant use. RESULTS: Results suggested that prescribed
      users more frequently reported side effects, compared to nonprescribed users. For
      prescribed users, females more frequently reported appetite, somatic, and anxiety
      related side effects compared to males. For nonprescribed users, while females
      reported more somatic and anxiety-related side effects, males more frequently
      reported loss of sex drive and sweating as side effects. Conclusions/Importance:
      These findings suggest prescribed users of psychostimulants more frequently
      report side effects with prominent gender differences in line with gender roles.

PMID- 27869566
TI  - Gastrointestinal comorbidities which complicate the treatment of anorexia
      nervosa.
AB  - Patients with anorexia nervosa often voice a multitude of symptoms in regards to
      their gastrointestinal tract. These complaints can complicate the treatment of
      their eating disorder as they distract attention from the important goal of
      weight restoration. Moreover, the restricting of certain food groups also makes
      the task of weight restoration substantially more difficult, or may result in
      binging. Therefore a working knowledge of common gastrointestinal comorbidities,
      such as celiac disease, irritable bowel syndrome, inflammatory bowel disease, and
      gastroparesis, is useful when treating a patient who has anorexia nervosa.

PMID- 27869567
TI  - Use of the Daily Phone Diary to Study Religiosity and Mood: Convergent Validity.
AB  - Studies of religious/spiritual behavior frequently rely on self-reported
      questionnaire data, which is susceptible to bias. The Daily Phone Diary (DPD) was
      developed to minimize bias in reporting activities and behavior across a 24-hour
      period. A cross-sectional study of 126 parents of children with cystic fibrosis
      was used to establish the validity of the DPD to study religious/spiritual
      behaviors. Longitudinal models were used to determine the odds of improved mood
      during religious/spiritual activities. Convergent validity was found.
      Participants had increased odds of improved mood during religious/spiritual
      activities compared to nonreligious/spiritual activities. Associations with
      gender and religious affiliations were found. The DPD is a valid tool for
      studying religious/spiritual activities and opens novel avenues for chaplaincy
      research and the development of chaplaincy interventions incorporating these
      findings.

PMID- 27869569
TI  - Change in expressed emotion and treatment outcome in adolescent anorexia nervosa.
AB  - Expressed emotion (EE) has been associated with poor outcomes in anorexia nervosa
      (AN); however, whether changes in EE predict superior treatment outcomes is
      unknown. The current study examined whether decreases in EE during an open trial
      of a novel family-based treatment for AN predicted symptoms at end of treatment.
      Forty-seven adolescents (12-18 years of age) with AN or sub-threshold AN and
      their parents (mothers: n = 47, fathers: n = 39) participated in 6 months of
      family treatment. Measures of AN symptomatology (Eating Disorder Examination
      completed by adolescent and end of treatment recovery status) and parental EE
      (Family Questionnaire completed by parents which measures two facets of EE:
      critical communication [CC] and emotional over-involvement [EOI]) were collected
      at baseline and end of treatment. Parental EOI, but not CC, significantly
      decreased during the course of treatment. Change in mothers', but not fathers',
      EE accounted for additional variance in AN symptomatology at end of treatment
      above baseline EE and baseline AN symptom levels. Findings suggest a greater
      emphasis on parent support during treatment may improve outcomes.

PMID- 27869568
TI  - The carrot and the stick? Strategies to improve compliance with college campus
      tobacco policies.
AB  - OBJECTIVE: Tobacco-free policies are being rapidly adopted nationwide, yet
      compliance with these policies remains a challenge. This study explored college
      campus key informants' experiences with tobacco policies, and their perceived
      benefits, drawbacks, and outcomes. PARTICIPANTS: The sample for this study was 68
      key informants representing 16 different California universities with varying
      tobacco policies (no smoking indoors and within 20 feet of entrances, designated
      smoking areas, 100% smoke-free, and 100% tobacco-free). METHODS: Qualitative,
      descriptive study. Semistructured interviews were transcribed verbatim and
      analyzed using content analysis. RESULTS: Strategies to improve compliance ranged
      from a social approach to a heavy focus on punitive enforcement. Key informants
      from campuses using a social approach alone reported barriers to improving
      compliance, including a perceived lack of efficacy of the approach. However,
      these campuses found it challenging to incorporate enforcement through campus
      police or security. CONCLUSIONS: College campus decision makers should explore
      using a combined approach (social approach as well as formal enforcement), with
      enforcement primarily the responsibility of nonpolice university channels (eg,
      Student Affairs, employee supervisors).

PMID- 27869570
TI  - Use of Primates in Research: What Do We Know About Captive Strepsirrhine
      Primates?
AB  - The increasing debate and restrictions on primate research have prompted many
      surveys about their status. However, there is a lack of information regarding
      strepsirrhine primates in the literature. This study provides an overview of
      research on strepsirrhines in captivity by analyzing scientific articles
      published from 2010 to 2013 and assessing publicly available government reports
      in Europe and the United States. Data on taxonomy, country, research area,
      research class, and type of institution were extracted. The 174 qualifying
      articles showed that species in the Galagidae and Cheirogaleidae families were
      used more often in invasive studies of neuroscience and metabolism, while the
      most commonly used species in noninvasive studies of behavior and cognition were
      true lemurs (family Lemuridae). France conducted the greatest number of invasive
      research projects, and the Duke Lemur Center was the institution with the most
      noninvasive studies. This study investigates how strepsirrhines are used in
      captive research and identifies issues in need of further review, which suggest
      that increased participation by the scientific community in the monitoring of
      strepsirrhine research is warranted.

PMID- 27869571
TI  - Enhancing Health Communication Outcomes Among Ethnic Minority Patients: The
      Effects of the Match Between Participation Preferences and Perceptions and Doctor
      Patient Concordance.
AB  - Ethnic minority patients are less participative in medical consultations compared
      to ethnic majority patients. It is thus important to find effective strategies to
      enhance ethnic minority patients' participation and improve subsequent health
      outcomes. This study therefore aimed to investigate the relation between the
      match between patients' preferred and perceived participation and doctor-patient
      concordance in preferred doctor-patient relationship on patient satisfaction,
      fulfillment of information needs, and understanding of information among Turkish
      Dutch and Dutch patients. Pre- and postconsultation questionnaires were filled
      out by 136 Dutch and 100 Turkish-Dutch patients in the waiting rooms of 32
      general practitioners (GPs). GPs completed a questionnaire too. Results showed
      that a match between patients' preferred and perceived participation was related
      to higher patient satisfaction, more fulfillment of information needs, and more
      understanding of information than a mismatch for both patient groups. For doctor
      patient concordance a conditional main effect on all outcome measures emerged
      only among Turkish-Dutch patients. That is, for patients who were discordant with
      their GP, higher perceived participation was related to lower satisfaction, worse
      fulfillment of information needs, and worse understanding of the information. In
      order to improve medical communication GPs should thus primarily be trained to
      tailor their communication styles to match patients' preferences for
      participation.

PMID- 27869572
TI  - Is listening to fat talk the same as participating in fat talk?
AB  - Our study examined whether verbally participating in fat talk conversations had a
      different effect on women's body image perception than merely listening to
      friends engage in fat talk conversations. Participants were 321 women who
      completed measures of listening to and participating in fat talk conversations,
      drive for thinness, body dissatisfaction, and dietary restraint. Results
      indicated that verbally participating in fat talk was a much stronger predictor
      of women's drive for thinness, body dissatisfaction, and dietary restraint than
      merely listening to friends engage in fat talk conversations.

PMID- 27869573
TI  - The chemokine, CXCL16, and its receptor, CXCR6, are constitutively expressed in
      human annulus fibrosus and expression of CXCL16 is up-regulated by exposure to IL
      1beta in vitro.
AB  - Chemokines are an important group of soluble molecules with specialized functions
      in inflammation. The roles of many specialized chemokines and their receptors
      remain poorly understood in the human intervertebral disc. We investigated CXCL16
      and its receptor, CXCR6, to determine their immunolocalization in disc tissue and
      their presence following exposure of cultured human annulus fibrosus cells to
      proinflammatory cytokines. CXCL16 is a marker for inflammation; it also can
      induce hypoxia-inducible factor 1alpha (HIF-1alpha), which is a phenotypic marker
      of heathy nucleus pulposus tissue. We found CXCL16 and CXCR6 immunostaining in
      many cells of the annulus portion of the disc. Molecular studies showed that
      annulus fibrosus cells exposed to IL-1beta, but not TNF-alpha, exhibited
      significant up-regulation of CXCL16 expression vs. control cells. There was no
      significant difference in the percentage of annulus cells that exhibited
      immunolocalization of CXCL16 in grade I/II, grade III or grade IV/V specimens.
      The presence of CXCL16 and its receptor, CXCR6, in the annulus in vivo suggests
      the need for future research concerning the role of this chemokine in
      proinflammatory functions, HIF-1alpha expression and disc vascularization.

PMID- 27869574
TI  - International Study of Chaplains' Attitudes About Research.
AB  - An online survey was conducted by twelve professional chaplain organizations to
      assess chaplains' attitudes about and involvement in research. A total of 2,092
      chaplains from 23 countries responded to the survey. Over 80% thought research
      was definitely important and nearly 70% thought chaplains should definitely be
      research literate. Just over 40% said they regularly read research articles and
      almost 60% said they occasionally did. The respondents rated their own research
      literacy as 6.5 on a 0-10 scale. Significant positive inter-correlations were
      found among all four measures: importance of (a) research and (b) research
      literacy; (c) frequency of reading articles; and (d) research literacy rating.
      Approximately 35% were never involved, 37% had been involved, 17% were currently
      involved, and 11% expected to be involved in research. The last three groups were
      significantly more likely to think research and research literacy were important
      and to read research articles than chaplains who were never involved in research.
      Given chaplains' interest in research, actions should be undertaken to facilitate
      further research engagement.

PMID- 27869575
TI  - Self-Affirmation Theory and Performance Feedback: When Scoring High Makes You
      Feel Low.
AB  - Video games have a wide variety of benefits for players. The current study
      examines how video games can also increase players' willingness to internalize
      important but threatening self-information. Research suggests that negative
      information regarding a valued self-image evokes defensive strategies aimed at
      dismissing or discrediting the source of information. Self-Affirmation Theory
      proposes that affirming or bolstering an important self-image unrelated to the
      previous threat can be an effective strategy for reducing defensiveness.
      Participants in the current study completed a fictitious intelligence test and
      received negative or no feedback, followed by 15 minutes of video game play that
      resulted in positive or no feedback. Results suggest that participants who valued
      video game success as part of their identity exhibited less defensive strategies
      in the form of increased test credibility ratings and lower self-perceptions of
      intelligence. This suggests that performing well on a video game is an
      affirmational resource for players whose identities are contingent upon such
      success. However, results also indicate that players who did not value video game
      success but received positive video game feedback exhibited more defensive
      reactions to the negative intelligence test feedback. This suggests that while
      players who value video game success as part of their identity may reap benefits
      from video game play after a self-threat, those who do not value such success may
      experience more harmful effects.

PMID- 27869576
TI  - Using Visual Metaphors in Health Messages: A Strategy to Increase Effectiveness
      for Mental Illness Communication.
AB  - Depression is highly prevalent among college students. Although treatment is
      often available on university campuses, many stigma-based barriers prevent
      students from seeking help. Communication strategies, such as the use of
      metaphors, are needed to reduce barriers. Specially, the use of visual metaphors,
      as a strategic message design tactic, may be an effective communication strategy
      to increase message appeal and engagement. Using a 2-phase approach, this study
      first identified common metaphors students use to conceptualize mental illness.
      Messages incorporating conceptual and visual metaphors were then designed and
      tested to determine their potential in reducing stigma. Participants (n = 256)
      were randomly assigned to 1 of 4 conditions in a between-subjects experiment:
      messages with visual and textual metaphors, messages with straightforward visuals
      and textual metaphors, text-based metaphor messages, or a control group. Overall,
      metaphorical messages are appealing, the use of visual metaphors leads to greater
      message engagement, and messages based on conceptual metaphors have the potential
      to reduce stigma. The use of conceptual and visual metaphors in campaign design
      is an effective strategy to communicate about a complex health topic, such as
      mental illness, and should be considered for use in campaigns to reduce barriers
      for help-seeking behavior.

PMID- 27869577
TI  - In this issue: Realising benefits and that informatics is all about the patient.
AB  - None.

PMID- 27869578
TI  - Open Source Paradigm: A Synopsis of The Cathedral and the Bazaar for Health and
      Social Care.
AB  - BACKGROUND: Open source software (OSS) is becoming more fashionable in health and
      social care, although the ideas are not new. However progress has been slower
      than many had expected. OBJECTIVE: The purpose is to summarise the Free/Libre
      Open Source Software (FLOSS) paradigm in terms of what it is, how it impacts
      users and software engineers and how it can work as a business model in health
      and social care sectors. METHOD: Much of this paper is a synopsis of Eric
      Raymond's seminal book The Cathedral and the Bazaar, which was the first
      comprehensive description of the open source ecosystem, set out in three long
      essays. Direct quotes from the book are used liberally, without reference to
      specific passages. The first part contrasts open and closed source approaches to
      software development and support. The second part describes the culture and
      practices of the open source movement. The third part considers business models.
      CONCLUSION: A key benefit of open source is that users can access and collaborate
      on improving the software if they wish. Closed source code may be regarded as a
      strategic business risk that that may be unacceptable if there is an open source
      alternative. The sharing culture of the open source movement fits well with that
      of health and social care.

PMID- 27869579
TI  - The acceptability to patients of video-consulting in general practice: semi
      structured interviews in three diverse general practices.
AB  - BACKGROUND: To improve patient access to healthcare, the UK government has
      encouraged technology-based approaches including internet video-consulting.
      However, little is known about patient acceptance of video-consulting as a
      consulting method. We aimed to explore primary care patients' views video
      consulting. METHOD: We used semi-structured interviews to survey 270 patients in
      NHS Lothian. Three diverse General Practices were chosen purposively and
      sequential patients attending the practice at a range of different times of day
      were invited to participate. Patients were asked to indicate their level of
      computer proficiency and provide their views on the use of video-call consulting
      and what specific applications it might have. We found that 135 of 270
      respondents (50%, 95% CI 43.9%-56.1%) would use video-consulting. Patients under
      60 years were over two times more likely to use it (OR 2.2, 95% CI 2.1-6.6, n =
      248) and evidence of a positive trend between increasing computer proficiency and
      those who would video-consult was found, (chi2 = 43.97, p < 0.0005, n=270).
      Patients who had previously used video-calling services (such as SkypeTM)were
      approximately six times more likely to favour video-consulting than those who had
      not (OR 5.9, 95% CI 3.5-9.9, n = 270). CONCLUSIONS: This suggests strong patient
      interest in video-consulting in primary care, however, it is possible that in the
      short to medium term there may be access inequality favouring younger and more
      technically able people. Further studies are needed to determine the content,
      safety, efficacy and cost-effectiveness of employing this medium.

PMID- 27869580
TI  - Qualitative analysis of multi-disciplinary round-table discussions on the
      acceleration of benefits and data analytics through hospital electronic
      prescribing (ePrescribing) systems.
AB  - BACKGROUND: Electronic systems that facilitate prescribing, administration and
      dispensing of medicines (ePrescribing systems) are at the heart of international
      efforts to improve the safety, quality and efficiency of medicine management.
      Considering the initial costs of procuring and maintaining ePrescribing systems,
      there is a need to better understand how to accelerate and maximise the financial
      benefits associated with these systems. OBJECTIVES: We sought to investigate how
      different sectors are approaching the realisation of returns on investment from
      ePrescribing systems in U.K. hospitals and what lessons can be learned for future
      developments and implementation strategies within healthcare settings. METHOD: We
      conducted international, multi-disciplinary, round-table discussions with 21
      participants from different backgrounds including policy makers, healthcare
      organisations, academic researchers, vendors and patient representatives. The
      discussions were audio-recorded, transcribed and then thematically analysed with
      the qualitative analysis software NVivo10. RESULTS: There was an over-riding
      concern that realising financial returns from ePrescribing systems was
      challenging. The underlying reasons included substantial fixed costs of care
      provision, the difficulties in radically changing the medicines management
      process and the lack of capacity within NHS hospitals to analyse and exploit the
      digital data being generated. Any future data strategy should take into account
      the need to collect and analyse local and national data (i.e. within and across
      hospitals), setting comparators to measure progress (i.e. baseline measurements)
      and clear standards guiding data management so that data are comparable across
      settings. CONCLUSIONS: A more coherent national approach to realising financial
      benefits from ePrescribing systems is needed as implementations progress and the
      range of tools to collect information will lead to exponential data growth. The
      move towards more sophisticated closed-loop systems that integrate prescribing,
      administration and dispensing, as well as increasingly empowered patients
      accessing their data through portals and portable devices, will accelerate these
      developments. Meaningful analysis of data will be the key to realise benefits
      associated with systems.

PMID- 27869581
TI  - Physical Activity in Ankylosing Spondylitis: evaluation and analysis of an
      eHealth tool.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory condition
      characterised by spinal arthritis and exercise is often recommended to reduce the
      symptoms and improve mobility. However, very little evidence exists for the value
      of exercise in AS. OBJECTIVES: Firstly, this pilot study aimed to evaluate an
      eHealth tool, the AS Observer, specifically designed to monitor symptoms, quality
      of life and physical activity in AS, in terms of patient experience and
      suitability in generating data for epidemiological studies. Secondly, it also
      investigated the collected data to determine if physical activity benefited
      individuals with AS. METHOD: The AS Observer was designed to enable weekly
      monitoring of AS symptoms and exercise using a web based platform. Participants
      with AS (n = 223) were recruited to use the AS observer. They provided baseline
      data and completed online weekly data entry for 12 weeks (e.g. Bath Ankylosing
      Spondylitis Activity Index (BASDAI), howRu, International Physical Activity
      Questionnaire (IPAQ)). Panel data analysis with fixed effects models investigated
      associations between variables. Activity type data and exit questionnaires were
      subjected to qualitative thematic analysis. RESULTS: In general, the AS Observer
      was well received and considered useful by participants, with 66% providing a
      positive response. The collected data suggested that IPAQ is inversely associated
      with total BASDAI, stiffness, tenderness and pain, but not fatigue. Stratified
      analysis demonstrated differential associations between BASDAI, IPAQ and howRU
      based on sex, HLA-B27 status and disease duration. Approximately half of the
      participants frequently did therapy and three-quarters undertook at least some
      vigorous activity ranging from formal exercise to recreation and (house) work.
      Despite some technical challenges, tool evaluation suggested that the AS Observer
      was a useful self-monitoring tool for participants. CONCLUSION: This pilot study
      demonstrated that increased exercise intensity and duration were associated with
      an improved BASDAI symptom score in a cohort of participants with AS.
      Furthermore, it provided further evidence of the value of using eHealth tools for
      clinical purposes and data collection for research, inclusive of the development
      of treatment pathways and disease management strategies.

PMID- 27869583
TI  - Patient-facing Technology for Identification of COPD in Primary Care.
AB  - BACKGROUND: The proliferation of mobile devices and emergence of interoperable
      'mHealth' apps is accelerating development and deployment of patient-facing risk
      assessments in primary care. The present study describes a user-centered design
      and an agile development approach to creation of an app for assessing
      lungfunction as part of a randomized controlled trial for the   dentification of
      chronic obstructive lung disease in primary care. METHOD: Seventeen patients
      recruited from a hospital-based, ambulatory family medicine clinic agreed to be
      videotaped while using the app, Lung Age, on a first-generation iPad prior to
      their provideR encounter. Subsequently, participants were interviewed using a
      semi-structured interview guide upon exiting their medical visit. RESULTS:
      Observational data indicated that participants took advantage of the portability
      and flexibility of the tablet device in the exam room to engage with the Lung Age
      app with the optionto share and discuss their results with their providers.
      Results from the semistructured interviews indicated that participants perceived
      the Lung Age app as intuitive and easy to use. CONCLUSIONS: These results
      demonstrate that tablet computers and mHealth apps can be used to deploy
      acceptable and useable electronic risk assessments in primary care settings.
      Future research focused on the impact and outcomes of patient-centered, mHealth
      apps for risk screening in primary care is warranted.

PMID- 27869582
TI  - Implementing and Using a Patient Portal: A qualitative exploration of patient and
      provider perspectives on engaging patients.
AB  - BACKGROUND: The use of portals might be expected to rise; however, adoption has
      been slow. Development of portals has occurred with limited patient involvement.
      This paper fills a need for literature concerning perspectives regarding the
      value of portals, how best to organize and provide portals, and critically how to
      seek patient involvement in implementation.ObjectiveThe objective was to explore
      the feelings, ideas, and expectations of patients and primary care providers
      concerning the implementation and use of patient portals. METHOD: The study
      employed a descriptive qualitative design interviewing seven patients and four
      providers from an interdisciplinary primary health care clinic in Ontario,
      Canada. Patients were older with at least one chronic condition. Interviews were
      analysed independently by three coders who then met to synthesize the findings.
      RESULTS: There was limited experience of portals and substantial convergence
      between patients and providers regarding concerns and potential benefits with an
      overall positive view. Four themes emerged: 1) the Context in which patient
      portal use takes place; 2) the Necessary conditions for use of a patient portal;
      3) the Implementation of a patient portal; and 4) the Use of a patient portal for
      care. CONCLUSIONS: Findings highlight that it is not sufficient to engage
      patients in the use of a portal; it is critical that patients be engaged in the
      early stages of implementation. With many health and fitness electronic tools
      available (e.g. Fitbit(c)), this study remind us that tools are not enough.
      Patient engagement requires patient-centred partnerships between patients and
      health care providers.

PMID- 27869584
TI  - The Melbourne East Monash General Practice Database (MAGNET): Using data from
      computerised medical records to create a platform for primary care and health
      services research.
AB  - The Melbourne East MonAsh GeNeral PracticE DaTabase (MAGNET) research platform
      was launched in 2013 to provide a unique data source for primary care and health
      services research in Australia.  MAGNET contains information from the
      computerised records of 50 participating general practices and includes data from
      the computerised medical records of more than 1,100,000 patients.  The data
      extracted is patient-level episodic information and includes a variety of fields
      related to patient demographics and historical clinical information, along with
      the characteristics of the participating general practices.  While there are
      limitations to the data that is currently available, the MAGNET research platform
      continues to investigate other avenues for improving the breadth and quality of
      data, with the aim of providing a more comprehensive picture of primary care in
      Australia.

PMID- 27869585
TI  - The critical components of an electronic care plan tool for primary care: an
      exploratory qualitative study.
AB  - BACKGROUND: A critical need exists for effective electronic tools that facilitate
      multidisciplinary care for complex patients in patient-centered medical
      homes.Objective To identify the essential components of a primary care (PC) based
      electronic care plan (ECP) tool that facilitates coordination of care for complex
      patients. METHOD: Three focus groups and nine semi-structured interviews were
      conducted at an academic PC practice in order to identify the ideal components of
      an ECP. RESULTS: Critical components of an ECP identified included: 1) patient
      background information, including patient demographics, care team member
      designation and key patient contacts, 2) user- and patient-centric task
      management functionalities, 3) a summary of a patient's care needs linked to the
      responsible member of the care team and 4) integration with the electronic
      medical record. We then designed an ECP mockup incorporating these components.
      CONCLUSION: Our investigation identified key principles that healthcare software
      developers can integrate into PC and patient-centered ECP tools.

PMID- 27869586
TI  - Hyperfamiliarity in Amnestic and Vascular Mild Cognitive Impairment.
AB  - OBJECTIVE: Hyperfamiliarity is a phenomenon where new stimuli are perceived as
      familiar. Previous studies have demonstrated familiarity disorder in mild
      cognitive impairment (MCI), but mostly from the perspective of a
      neuropsychological approach, and the exact correlation of MCI aetiologies with
      the phenomenon remains uncertain. Based on current evidence suggesting a frontal
      subcortical pathway contributing to familiarity processing, we hypothesize that
      individuals with a vascular aetiology of MCI will likely suffer more familiarity
      deficits. This study aims to examine the real-life hyperfamiliarity symptoms in
      amnestic versus vascular MCI. METHODS: Informants of 11 amnestic and 9 vascular
      cognitive impairment patients were interviewed about the frequency of
      hyperfamiliarity symptoms in the previous month. MRI brain images of vascular
      cognitive impairment patients were analysed as well. RESULTS: Patients with
      vascular cognitive impairment with no dementia (VCIND) showed a significantly
      higher frequency of hyperfamiliarity for people but not places or objects. Within
      VCIND patients, overall basal ganglia hyperintensities, particularly in the
      putamen, were found to significantly correlate to hyperfamiliarity. CONCLUSIONS:
      Patients with VCIND suffer more real-life hyperfamiliarity during people
      recognition compared to patients with amnestic mild cognitive impairment (aMCI),
      despite a comparative global decline in cognitive. This is likely due to impaired
      memory retrieval and matching processes resulting from subcortical ischaemic
      lesions.

PMID- 27869587
TI  - Tuberculosis-Associated Death among Adult Wild Boars, Spain, 2009-2014.
AB  - We investigated adult Eurasian wild boar (Sus scrofa) survival and death in 2
      tuberculosis-endemic populations with different harvest pressure in Spain.
      Overall, tuberculosis accounted for 30% of total deaths. Increased survival in
      protected areas has direct implications for wild boar management and tuberculosis
      control.

PMID- 27869588
TI  - Human Infection with Novel Spotted Fever Group Rickettsia Genotype, China, 2015.
AB  - Only 4 species of spotted fever group rickettsiae have been detected in humans in
      China. However, phylogenetic analysis of samples from 5 ill patients in China
      indicated infection with a novel spotted fever group Rickettsia, designated
      Rickettsia sp. XY99. Clinical signs resembled those of severe fever with
      thrombocytopenia syndrome.

PMID- 27869589
TI  - Rift Valley Fever Outbreak in Livestock, Mozambique, 2014.
AB  - In early 2014, abortions and death of ruminants were reported on farms in Maputo
      and Gaza Provinces, Mozambique. Serologic analysis and quantitative and
      conventional reverse transcription PCR confirmed the presence of Rift Valley
      fever virus. The viruses belonged to lineage C, which is prevalent among Rift
      Valley fever viruses in southern Africa.

PMID- 27869590
TI  - Detection and Genotyping of Coxiella burnetii in Pigs, South Korea, 2014-2015.
AB  - We assessed Coxiella burnetii prevalence and genotypes in pigs in South Korea
      during 2014-2015. Prevalence was low among 1,030 samples tested by ELISA and
      immunofluorescent assay and 1,124 samples tested by PCR. Despite this finding,
      possible transmission of C. burnetii from pigs to humans cannot be excluded.

PMID- 27869592
TI  - Assessing the Epidemic Potential of RNA and DNA Viruses.
AB  - Many new and emerging RNA and DNA viruses are zoonotic or have zoonotic origins
      in an animal reservoir that is usually mammalian and sometimes avian. Not all
      zoonotic viruses are transmissible (directly or by an arthropod vector) between
      human hosts. Virus genome sequence data provide the best evidence of
      transmission. Of human transmissible virus, 37 species have so far been
      restricted to self-limiting outbreaks. These viruses are priorities for
      surveillance because relatively minor changes in their epidemiologies can
      potentially lead to major changes in the threat they pose to public health. On
      the basis of comparisons across all recognized human viruses, we consider the
      characteristics of these priority viruses and assess the likelihood that they
      will further emerge in human populations. We also assess the likelihood that a
      virus that can infect humans but is not capable of transmission (directly or by a
      vector) between human hosts can acquire that capability.

PMID- 27869593
TI  - Evaluating Healthcare Claims for Neurocysticercosis by Using All-Payer All-Claims
      Data, Oregon, 2010-2013.
AB  - To characterize the frequency of neurocysticercosis, associated diagnostic codes,
      and place of infection, we searched Oregon's All Payer All-Claims dataset for
      2010-2013. Twice as many cases were found by searching inpatient and outpatient
      data than by inpatient data alone. Studies relying exclusively on inpatient data
      underestimate frequency and miss less severe disease.

PMID- 27869591
TI  - Vertebrate Host Susceptibility to Heartland Virus.
AB  - Heartland virus (HRTV) is a recently described phlebovirus initially isolated in
      2009 from 2 humans who had leukopenia and thrombocytopenia. Serologic assessment
      of domestic and wild animal populations near the residence of 1 of these persons
      showed high exposure rates to raccoons, white-tailed deer, and horses. To our
      knowledge, no laboratory-based assessments of viremic potential of animals
      infected with HRTV have been performed. We experimentally inoculated several
      vertebrates (raccoons, goats, chickens, rabbits, hamsters, C57BL/6 mice, and
      interferon-alpha/beta/gamma receptor-deficient [Ag129]) mice with this virus. All
      animals showed immune responses against HRTV after primary or secondary exposure.
      However, neutralizing antibody responses were limited. Only Ag129 mice showed
      detectable viremia and associated illness and death, which were dose dependent.
      Ag129 mice also showed development of mean peak viral antibody titers >8 log10
      PFU/mL, hemorrhagic hepatic lesions, splenomegaly, and large amounts of HRTV
      antigen in mononuclear cells and hematopoietic cells in the spleen.

PMID- 27869594
TI  - Horizontal Transmission of Chronic Wasting Disease in Reindeer.
AB  - We challenged reindeer by the intracranial route with the agent of chronic
      wasting disease sourced from white-tailed deer, mule deer, or elk and tested for
      horizontal transmission to naive reindeer. Reindeer were susceptible to chronic
      wasting disease regardless of source species. Horizontal transmission occurred
      through direct contact or indirectly through the environment.

PMID- 27869595
TI  - Infectious Dose of Listeria monocytogenes in Outbreak Linked to Ice Cream, United
      States, 2015.
AB  - The relationship between the number of ingested Listeria monocytogenes cells in
      food and the likelihood of developing listeriosis is not well understood. Data
      from an outbreak of listeriosis linked to milkshakes made from ice cream produced
      in 1 factory showed that contaminated products were distributed widely to the
      public without any reported cases, except for 4 cases of severe illness in
      persons who were highly susceptible. The ingestion of high doses of L.
      monocytogenes by these patients infected through milkshakes was unlikely if
      possible additional contamination associated with the preparation of the
      milkshake is ruled out. This outbreak illustrated that the vast majority of the
      population did not become ill after ingesting a low level of L. monocytogenes but
      raises the question of listeriosis cases in highly susceptible persons after
      distribution of low-level contaminated products that did not support the growth
      of this pathogen.

PMID- 27869596
TI  - Unusual Ebola Virus Chain of Transmission, Conakry, Guinea, 2014-2015.
AB  - In October 2015, a new case of Ebola virus disease in Guinea was detected. Case
      investigation, serology, and whole-genome sequencing indicated possible
      transmission of the virus from an Ebola virus disease survivor to another person
      and then to the case-patient reported here. This transmission chain over 11
      months suggests slow Ebola virus evolution.

PMID- 27869597
TI  - Digital PCR for Quantifying Norovirus in Oysters Implicated in Outbreaks, France.
AB  - Using samples from oysters clearly implicated in human disease, we quantified
      norovirus levels by using digital PCR. Concentrations varied from 43 to 1,170 RNA
      copies/oyster. The analysis of frozen samples from the production area showed the
      presence of norovirus 2 weeks before consumption.

PMID- 27869598
TI  - Highly Divergent Dengue Virus Type 2 in Traveler Returning from Borneo to
      Australia.
AB  - Dengue virus type 2 was isolated from a tourist who returned from Borneo to
      Australia. Phylogenetic analysis identified this virus as highly divergent and
      occupying a basal phylogenetic position relative to all known human and sylvatic
      dengue virus type 2 strains and the most divergent lineage not assigned to a new
      serotype.

PMID- 27869599
TI  - Streptococcus agalactiae Serotype IV in Humans and Cattle, Northern Europe1.
AB  - Streptococcus agalactiae is an emerging pathogen of nonpregnant human adults
      worldwide and a reemerging pathogen of dairy cattle in parts of Europe. To learn
      more about interspecies transmission of this bacterium, we compared
      contemporaneously collected isolates from humans and cattle in Finland and
      Sweden. Multilocus sequence typing identified 5 sequence types (STs) (ST1, 8, 12,
      23, and 196) shared across the 2 host species, suggesting possible interspecies
      transmission. More than 54% of the isolates belonged to those STs. Molecular
      serotyping and pilus island typing of those isolates did not differentiate
      between populations isolated from different host species. Isolates from humans
      and cattle differed in lactose fermentation, which is encoded on the accessory
      genome and represents an adaptation to the bovine mammary gland. Serotype IV
      ST196 isolates were obtained from multiple dairy herds in both countries. Cattle
      may constitute a previously unknown reservoir of this strain.

PMID- 27869600
TI  - Reemergence of St. Louis Encephalitis Virus, California, 2015.
AB  - St. Louis encephalitis virus infection was detected in summer 2015 in southern
      California after an 11-year absence, concomitant with an Arizona outbreak.
      Sequence comparisons showed close identity of California and Arizona isolates
      with 2005 Argentine isolates, suggesting introduction from South America and
      underscoring the value of continued arbovirus surveillance.

PMID- 27869601
TI  - Detection of Vaccinia Virus in Dairy Cattle Serum Samples from 2009, Uruguay.
AB  - We detected orthopoxvirus in 28 of 125 serum samples collected during 2009 from
      cattle in Uruguay. Two samples were PCR-positive for vaccinia virus and had
      sequences similar to those for vaccinia virus associated with outbreaks in
      Brazil. Autochthonous circulation of vaccinia virus in Uruguay and other South
      American countries cannot be ruled out.

PMID- 27869602
TI  - Secondary Shiga Toxin-Producing Escherichia coli Infection, Japan, 2010-2012.
AB  - To evaluate the potential public health risk caused by secondary Shiga toxin
      producing Escherichia coli (STEC) infections in Japan, we investigated the
      prevalence and characteristics of STEC isolated from healthy adults during 2010
      2012. Although prevalence among healthy adults was high, most STEC organisms
      displayed characteristics rarely found in isolates from symptomatic patients.

PMID- 27869603
TI  - Hepatitis E Virus in Yellow Cattle, Shandong, Eastern China.

PMID- 27869605
TI  - Schmallenberg Virus in Zoo Ruminants, France and the Netherlands.

PMID- 27869604
TI  - Molecular, Spatial, and Field Epidemiology Suggesting TB Transmission in
      Community, Not Hospital, Gaborone, Botswana.
AB  - During 2012-2015, 10 of 24 patients infected with matching genotypes of
      Mycobacterium tuberculosis received care at the same hospital in Gaborone,
      Botswana. Nosocomial transmission was initially suspected, but we discovered
      plausible sites of community transmission for 20 (95%) of 21 interviewed
      patients. Active case-finding at these sites could halt ongoing transmission.

PMID- 27869606
TI  - Pathogenic Lineage of mcr-Negative Colistin-Resistant Escherichia coli, Japan,
      2008-2015.

PMID- 27869607
TI  - New Hepatitis E Virus Genotype in Bactrian Camels, Xinjiang, China, 2013.

PMID- 27869608
TI  - Dual Emergence of Usutu Virus in Common Blackbirds, Eastern France, 2015.

PMID- 27869609
TI  - Introgressed Animal Schistosomes Schistosoma curassoni and S. bovis Naturally
      Infecting Humans.

PMID- 27869611
TI  - Chlamydia-Related Bacteria in Free-Living and Captive Great Apes, Gabon.

PMID- 27869610
TI  - Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial,
      Guinea, 2015.
AB  - By using data from a 2015 clinical trial on Ebola convalescent-phase plasma in
      Guinea, we assessed the prevalence of electrolyte and metabolic abnormalities at
      admission and their predictive value to stratify patients into risk groups.
      Patients underwent testing with a point-of-care device. We used logistic
      regression to construct a prognostic model and summarized the predictive value
      with the area under the receiver operating curve. Abnormalities were common among
      patients, particularly hypokalemia, hypocalcemia, hyponatremia, raised
      creatinine, high anion gap, and anemia. Besides age and PCR cycle threshold
      value, renal dysfunction, low calcium levels, and low hemoglobin levels were
      independently associated with increased risk for death. A prognostic model using
      all 5 factors was highly discriminatory (area under the receiver operating curve
      0.95; 95% CI 0.90-0.99) and enabled the definition of risk criteria to guide
      targeted care. Most patients had a very low (<5%) or very high (>80%) risk for
      death.

PMID- 27869612
TI  - Baylisascaris procyonis Roundworm Seroprevalence among Wildlife Rehabilitators,
      United States and Canada, 2012-2015.
AB  - Baylisascaris procyonis roundworms can cause potentially fatal neural larva
      migrans in many species, including humans. However, the clinical spectrum of
      baylisascariasis is not completely understood. We tested 347 asymptomatic adult
      wildlife rehabilitators for B. procyonis antibodies; 24 were positive, suggesting
      that subclinical baylisascariasis is occurring among this population.

PMID- 27869613
TI  - Effect of Live Poultry Market Interventions on Influenza A(H7N9) Virus,
      Guangdong, China.
AB  - Since March 2013, three waves of human infection with avian influenza A(H7N9)
      virus have been detected in China. To investigate virus transmission within and
      across epidemic waves, we used surveillance data and whole-genome analysis of
      viruses sampled in Guangdong during 2013-2015. We observed a geographic shift of
      human A(H7N9) infections from the second to the third waves. Live poultry market
      interventions were undertaken in epicenter cities; however, spatial phylogenetic
      analysis indicated that the third-wave outbreaks in central Guangdong most likely
      resulted from local virus persistence rather than introduction from elsewhere.
      Although the number of clinical cases in humans declined by 35% from the second
      to the third waves, the genetic diversity of third-wave viruses in Guangdong
      increased. Our results highlight the epidemic risk to a region reporting
      comparatively few A(H7N9) cases. Moreover, our results suggest that live-poultry
      market interventions cannot completely halt A(H7N9) virus persistence and
      dissemination.

PMID- 27869614
TI  - Cutaneous Granulomas in Dolphins Caused by Novel Uncultivated Paracoccidioides
      brasiliensis.
AB  - Cutaneous granulomas in dolphins were believed to be caused by Lacazia loboi,
      which also causes a similar disease in humans. This hypothesis was recently
      challenged by reports that fungal DNA sequences from dolphins grouped this
      pathogen with Paracoccidioides brasiliensis. We conducted phylogenetic analysis
      of fungi from 6 bottlenose dolphins (Tursiops truncatus) with cutaneous
      granulomas and chains of yeast cells in infected tissues. Kex gene sequences of
      P. brasiliensis from dolphins showed 100% homology with sequences from cultivated
      P. brasiliensis, 73% with those of L. loboi, and 93% with those of P. lutzii.
      Parsimony analysis placed DNA sequences from dolphins within a cluster with human
      P. brasiliensis strains. This cluster was the sister taxon to P. lutzii and L.
      loboi. Our molecular data support previous findings and suggest that a novel
      uncultivated strain of P. brasiliensis restricted to cutaneous lesions in
      dolphins is probably the cause of lacaziosis/lobomycosis, herein referred to as
      paracoccidioidomycosis ceti.

PMID- 27869615
TI  - Highly Pathogenic Influenza A(H5Nx) Viruses with Altered H5 Receptor-Binding
      Specificity.
AB  - Emergence and intercontinental spread of highly pathogenic avian influenza
      A(H5Nx) virus clade 2.3.4.4 is unprecedented. H5N8 and H5N2 viruses have caused
      major economic losses in the poultry industry in Europe and North America, and
      lethal human infections with H5N6 virus have occurred in Asia. Knowledge of the
      evolution of receptor-binding specificity of these viruses, which might affect
      host range, is urgently needed. We report that emergence of these viruses is
      accompanied by a change in receptor-binding specificity. In contrast to ancestral
      clade 2.3.4 H5 proteins, novel clade 2.3.4.4 H5 proteins bind to fucosylated
      sialosides because of substitutions K222Q and S227R, which are unique for highly
      pathogenic influenza virus H5 proteins. North American clade 2.3.4.4 virus
      isolates have retained only the K222Q substitution but still bind fucosylated
      sialosides. Altered receptor-binding specificity of virus clade 2.3.4.4 H5
      proteins might have contributed to emergence and spread of H5Nx viruses.

PMID- 27869617
TI  - HIV-1 Subtype C, Tenofovir, and the Relationship With Treatment Failure and Drug
      Resistance.

PMID- 27869618
TI  - Meaningful Thresholds for the Volume-Outcome Relationship in Total Knee
      Arthroplasty.
AB  - BACKGROUND: Increasing evidence supports the finding that patients undergoing a
      total knee arthroplasty with high-volume physicians and hospitals achieve better
      outcomes. Unfortunately, the existing definitions for high-volume surgeons and
      hospitals are highly variable and entirely arbitrary. The aim of this study was
      to identify a set of meaningful hospital and surgeon total knee arthroplasty
      volume thresholds. METHODS: Using 289,976 patients undergoing primary total knee
      arthroplasty from an administrative database, we applied stratum-specific
      likelihood ratio (SSLR) analysis of a receiver operating characteristic (ROC)
      curve to generate sets of volume thresholds most predictive of adverse outcomes.
      The outcomes considered for surgeon volume included 90-day complication and 2
      year revision. For hospital volume, we considered 90-day complications and 90-day
      mortality. RESULTS: SSLR analysis of the ROC curves for 90-day complication and 2
      year revision rates by surgeon volume identified four volume categories: 0 to 12,
      13 to 59, 60 to 145, and >=146 total knee arthroplasties per year. Complication
      rates decreased significantly (p < 0.05) in progressively higher-volume
      categories. Revision rates followed a similar pattern, but did not decrease
      between surgeons performing 60 to 145 arthroplasties per year and those
      performing >=146 arthroplasties per year. SSLR analysis of 90-day complication
      and 90-day mortality rates by hospital volume also identified four volume
      categories: 0 to 89, 90 to 235, 236 to 644, and >=645 total knee arthroplasties
      per year. Complication rates decreased significantly (p < 0.05) in progressively
      higher-volume categories, but the rates did not decrease between hospitals
      performing 236 to 644 arthroplasties per year and those performing >=645
      arthroplasties per year. Mortality rates for hospitals with >=645 total knee
      arthroplasties per year were significantly lower (p < 0.05) than those below the
      threshold. CONCLUSIONS: Our study supports the use of SSLR analysis of ROC curves
      for risk-based volume stratification in total knee arthroplasty volume-outcomes
      research. SSLR analysis established meaningful volume definitions for low,
      medium, high, and very high-volume total knee arthroplasty surgeons and
      hospitals. This should help patients, surgeons, hospitals, and policymakers to
      make decisions with regard to the optimal delivery of total knee arthroplasty.
      LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 27869616
TI  - Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA
      modification and chromatin accessibility.
AB  - Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA
      demethylation and generating new epigenetic marks. Here we show that concomitant
      loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B
      cell transition in the bone marrow, decreased Irf4 expression and impaired the
      germline transcription and rearrangement of the Igkappa locus. Tet2/3-deficient
      pro-B cells showed increased CpG methylation at the Igkappa 3' and distal
      enhancers that was mimicked by depletion of E2A or PU.1, as well as a global
      decrease in chromatin accessibility at enhancers. Importantly, re-expression of
      the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation
      of the Igkappa enhancers and restored their chromatin accessibility. Our data
      suggest that TET proteins and lineage-specific transcription factors cooperate to
      influence chromatin accessibility and Igkappa enhancer function by modulating the
      modification status of DNA.

PMID- 27869619
TI  - Five-Year Survival of 20,946 Unicondylar Knee Replacements and Patient Risk
      Factors for Failure: An Analysis of German Insurance Data.
AB  - BACKGROUND: Improvements in implant design and surgical technique of unicondylar
      knee arthroplasty have led to reduced revision rates, but patient selection seems
      to be crucial for success of such arthroplasties. The purpose of the present
      study was to analyze the 5-year implant survival rate of unicondylar knee
      replacements in Germany and to identify patient factors associated with an
      increased risk of revision, including >30 comorbid conditions. METHODS: Using
      nationwide billing data of the largest German health-care insurance for inpatient
      hospital treatment, we identified patients who underwent unicondylar knee
      arthroplasty between 2006 and 2012. Kaplan-Meier survival curves with revision as
      the end point and log-rank tests were used to evaluate 5-year implant survival. A
      multivariable Cox regression model was used to determine factors associated with
      revision. The risk factors of age, sex, diagnosis, comorbidities, type of implant
      fixation, and hospital volume were analyzed. Hazard ratios (HRs) and 95%
      confidence intervals (95% CIs) were calculated. RESULTS: During the study period,
      a total of 20,946 unicondylar knee arthroplasties were included. The number of
      unicondylar knee arthroplasties per year increased during the study period from
      2,527 in 2006 to 4,036 in 2012. The median patient age was 64 years
      (interquartile range, 56 to 72 years), and 60.4% of patients were female. During
      the time evaluated, the 1-year revision rate decreased from 14.3% in 2006 to 8.7%
      in 2011. The 5-year survival rate was 87.8% (95% CI, 87.3% to 88.3%). Significant
      risk factors (p < 0.05) for unicondylar knee arthroplasty revision were younger
      age (the HR was 2.93 [95% CI, 2.48 to 3.46] for patient age of <55 years, 1.86
      [95% CI, 1.58 to 2.19] for 55 to 64 years, and 1.52 [95% CI, 1.29 to 1.79] for 65
      to 74 years; patient age of >74 years was used as the reference); female sex (HR,
      1.18 [95% CI, 1.07 to 1.29]); complicated diabetes (HR, 1.47 [95% CI, 1.03 to
      2.12]); depression (HR, 1.29 [95% CI, 1.06 to 1.57]); obesity, defined as a body
      mass index of >=30 kg/m2 (HR, 1.13 [95% CI, 1.02 to 1.26]); and low-volume
      hospitals, denoted as an annual hospital volume of <=10 cases (HR, 1.60 [95% CI,
      1.39 to 1.84]), 11 to 20 cases (HR, 1.47 [95% CI, 1.27 to 1.70]), and 21 to 40
      cases (HR, 1.31 [95% CI, 1.14 to 1.51]) (>40 cases was used as the reference).
      CONCLUSIONS: Apart from known risk factors, this study showed a significant
      negative influence of obesity, depression, and complicated diabetes on the 5-year
      unicondylar knee replacement survival rate. Surgical indications and preoperative
      patient counseling should consider these findings. LEVEL OF EVIDENCE: Prognostic
      Level III. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 27869620
TI  - Safety and Outcomes of Inpatient Compared with Outpatient Surgical Procedures for
      Ankle Fractures.
AB  - BACKGROUND: As the cost of health-care delivery rises in the era of bundled
      payments for care, there is an impetus toward minimizing hospitalization.
      Evidence to support the safety of open reduction and internal fixation (ORIF) of
      ankle fractures in the outpatient setting is largely anecdotal. METHODS: Patients
      who underwent ORIF from 2005 to 2013 were identified via postoperative diagnoses
      of ankle fracture and Current Procedural Terminology codes; patients with open
      fractures and patients who were emergency cases were excluded. Patients
      undergoing inpatient and outpatient surgical procedures were propensity score
      matched to reduce differences in the baseline characteristics. Primary tracked
      outcomes included medical and surgical complications, readmission, and
      reoperation within 30 days of the procedure. Binary logistic regression models
      were created that determined the risk-adjusted relationship between admission
      status and primary outcomes. RESULTS: Outpatient surgical procedures were
      associated with lower rates of urinary tract infection (0.4% compared with 0.9%;
      p = 0.041), pneumonia (0.0% compared with 0.5%; p = 0.002), venous thromboembolic
      events (0.3% compared with 0.8%; p = 0.049), and bleeding requiring transfusion
      (0.1% compared with 0.6%; p = 0.012). Outpatient status was independently
      associated with reduced 30-day medical morbidity (odds ratio, 0.344 [95%
      confidence interval, 0.201 to 0.589]). No significant differences were uncovered
      with respect to surgical complications (p = 0.076), unplanned reoperations (p =
      0.301), and unplanned readmissions (p = 0.358). CONCLUSIONS: In patients with
      closed fractures and minimal comorbidities, outpatient ORIF was associated with
      reduced risk of select 30-day medical morbidity and no difference in surgical
      morbidity, reoperations, and readmissions relative to inpatient. Factors
      unaccounted for when creating matched cohorts may impact our results. Our
      findings lend reassurance to surgeons who defer admission for low-risk patients.
      LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 27869621
TI  - Ponseti Treatment of Rigid Residual Deformity in Congenital Clubfoot After
      Walking Age.
AB  - BACKGROUND: There is no established treatment for rigid residual deformity of
      congenital clubfoot (CCF) after walking age. Soft-tissue procedures, osseous
      procedures, and external fixation have been performed with unpredictable results.
      We applied the Ponseti method to patients with this condition in order to improve
      the outcomes of treatment. METHODS: We retrospectively reviewed the cases of 44
      patients (68 feet) with congenital clubfoot whose mean age (and standard
      deviation) at treatment was 4.8 +/- 1.6 years. All patients had been previously
      treated in other institutions by various conservative and surgical protocols.
      Residual deformity was evaluated using the International Clubfoot Study Group
      Score (ICFSGS), and stiffness was rated by the number of casts needed for
      deformity correction. Ponseti manipulation and cast application was performed.
      Equinus was usually treated with percutaneous heel-cord surgery, while the cavus
      deformity was treated with percutaneous fasciotomy when needed. Tibialis anterior
      tendon transfer (TATT) was performed in patients over 3 years old. At the time of
      follow-up, the results were evaluated using the ICFSGS. RESULTS: Before
      treatment, 12 feet were graded as fair and 56, as poor. Two to 4 casts were
      applied, with each cast worn for 4 weeks. Stiffness was moderate (2 casts) in 23
      feet, severe (3 casts) in 30 feet, and very severe (4 casts) in 15 feet.
      Percutaneous heel-cord surgery was performed in 28 feet; open posterior release,
      in 5 feet; plantar fasciotomy, in 30 feet; and TATT, in 60 feet. The mean length
      of follow-up was 4.9 +/- 1.8 years. Eight feet had an excellent result; 49 feet,
      a good result; and 11 feet, a fair result. No patient had pain. All of the feet
      showed significant improvement. CONCLUSIONS: Ponseti treatment with TATT, which
      was performed in 88% of the feet, was effective, and satisfactory results were
      achieved in 84% of the feet. At the time of follow-up, no patient showed an
      abnormal gait, all feet were plantigrade and flexible, but 2 feet (2.9%) had
      relapsed. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 27869622
TI  - ACL Deficiency Increases Forces on the Medial Femoral Condyle and the Lateral
      Meniscus with Applied Rotatory Loads.
AB  - BACKGROUND: The articular surfaces and menisci act with the anterior cruciate
      ligament (ACL) to stabilize the knee joint. Their role in resisting applied
      rotatory loads characteristic of instability events is unclear despite commonly
      observed damage to these intra-articular structures in the acute and chronic ACL
      injury settings. METHODS: Ten fresh-frozen human cadaveric knees were mounted to
      a robotic manipulator. Combined valgus and internal rotation torques were applied
      in the presence and absence of a 300-N compressive load. Forces carried by the
      individual menisci and via cartilage-to-cartilage contact on each femoral condyle
      in ACL-intact and ACL-sectioned states were measured using the principle of
      superposition. RESULTS: In response to applied valgus and internal rotation
      torques in the absence of compression, sectioning of the ACL increased the net
      force carried by the lateral meniscus by at most 65.8 N (p < 0.001). Moreover,
      the anterior shear force carried by the lateral meniscus increased by 25.7 N (p <
      0.001) and 36.5 N (p = 0.042) in the absence and presence of compression,
      respectively. In response to applied valgus and internal rotation torques,
      sectioning of the ACL increased the net force carried by cartilage-to-cartilage
      contact on the medial femoral condyle by at most 38.9 N (p = 0.006) and 46.7 N (p
      = 0.040) in the absence and presence of compression, respectively. Additionally,
      the lateral shear force carried by cartilage-to-cartilage contact on the medial
      femoral condyle increased by at most 21.0 N (p = 0.005) and by 28.0 N (p = 0.025)
      in the absence and presence of compression, respectively. Forces carried by the
      medial meniscus and by cartilage-to-cartilage contact on the lateral femoral
      condyle changed by <5 N as a result of ACL sectioning. CONCLUSIONS: ACL
      sectioning increased the net forces carried by the lateral meniscus and medial
      femoral condyle-and the anterior shear and lateral shear forces, respectively-in
      response to multiplanar valgus and internal rotation torque. CLINICAL RELEVANCE:
      These loading patterns provide a biomechanical rationale for clinical patterns of
      intra-articular derangement such as lateral meniscal injury and osseous
      remodeling of the medial compartment seen with ACL insufficiency.

PMID- 27869623
TI  - Contamination of the Surgical Field with Propionibacterium acnes in Primary
      Shoulder Arthroplasty.
AB  - BACKGROUND: Propionibacterium acnes is a common pathogen identified in
      postoperative shoulder infection. It has been shown to be present in culture
      specimens during primary shoulder arthroplasty; however, recent work has
      suggested that it is most likely to be a contaminant. Our aim was to identify the
      potential sources of contamination in shoulder arthroplasty. METHODS: Tissue
      swabs were obtained for microbiological analysis from consecutive patients
      undergoing primary shoulder arthroplasty. Routine surgical technique was
      maintained, and 5 specimens were taken from different sites: (1) the subdermal
      layer, (2) the tip of the surgeon's glove, (3) the inside scalpel blade (used for
      deeper incision), (4) the forceps, and (5) the outside scalpel blade (used for
      the skin incision). RESULTS: Forty patients (25 female patients and 15 male
      patients) were included. Thirteen (33%) of the 40 patients had at least 1 culture
      specimen positive for P. acnes. Two (8%) of the 25 female patients and 11 (73%)
      of the 15 male patients had >=1 culture specimen positive for P. acnes. The most
      common site of growth of P. acnes was the subdermal layer (12 positive samples),
      followed by the forceps (7 positive samples), the tip of the surgeon's glove (7
      positive samples), the outside scalpel blade (4 positive samples), and the inside
      scalpel blade (1 positive sample). There were 27 of 75 swabs that were positive
      on culture for P. acnes in male patients compared with 4 of 125 swabs in female
      patients. Male patients had 66 times (95% confidence interval, 6 to 680 times)
      higher odds of having a positive culture indicating subdermal colonization
      compared with female patients (p < 0.001). CONCLUSIONS: P. acnes is a common
      contaminant of the surgical field in primary shoulder arthroplasty. The subdermal
      layer may be the source of this contamination, and the prevalence of P. acnes in
      the surgical wound may be due to the surgeon's manipulation with gloves and
      instruments. Our findings are consistent with those regarding the increased rates
      of P. acnes bacterial load and intraoperative growth in male patients compared
      with female patients. CLINICAL RELEVANCE: P. acnes is likely to be spread
      throughout the surgical field from the subdermal layer via soft-tissue handling
      by the surgeon and instruments. Strategies need to be utilized to minimize this
      contact and to reduce the chance of colonization.

PMID- 27869624
TI  - Surgical Outcome and Prognostic Analysis of Transoral Atlantoaxial Reduction
      Plate System for Basilar Invagination: A Voxel-Based Morphometry Study.
AB  - BACKGROUND: The use of a transoral atlantoaxial reduction plate (TARP) system is
      an effective surgical approach for the treatment of basilar invagination. With
      the aim of improving the therapeutic efficacy of the TARP operation, we conducted
      a voxel-based morphometric study to quantitatively investigate the descent of the
      odontoid process and craniocervical volume changes. METHODS: We enrolled 20
      patients with basilar invagination who underwent a TARP procedure. Craniocervical
      computed tomography (CT) scanning and a 3-dimensional (3-D) reconstruction of the
      craniocervical junction were performed. Craniocervical volumes and odontoid
      process descent distances were measured preoperatively and postoperatively.
      Individual neurological function was evaluated according to the Japanese
      Orthopaedic Association (JOA) scoring system for cervical disorders. Pearson
      correlation analysis was applied for statistical testing. RESULTS: Surgical
      efficacy (the JOA-score improvement rate) was significantly associated with the
      craniocervical volume improvement rate, the odontoid descent distance, and the
      absolute craniocervical volume changes (p < 0.01 for all), with correlation
      coefficients (r) of 0.83, 0.80, and 0.61, respectively. No significant
      correlation was noted between surgical efficacy and age, symptom duration,
      preoperative neurological function, odontoid process displacement, or change in
      clivus-odontoid angle (p > 0.05). The craniocervical volume improvement rate was
      significantly associated with the odontoid descent distance (r = 0.8; p < 0.01),
      but it was not associated with the odontoid displacement or the change in the
      clivus-odontoid angle (p > 0.05). CONCLUSIONS: We found that the odontoid descent
      distance predicted the craniocervical volume improvement rate following TARP
      procedures in patients with basilar invagination, and we believe that both can
      serve as predictors of surgical efficacy. We believe that planning the odontoid
      descent distance preoperatively may help to improve the efficacy of TARP
      operations. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 27869625
TI  - Asymptomatic Pseudotumors in Patients with Taper Corrosion of a Dual-Taper
      Modular Femoral Stem: MARS-MRI and Metal Ion Study.
AB  - BACKGROUND: Modularity in total hip arthroplasty facilitates intraoperative
      restoration of patient anatomy. Although dual-taper modular total hip
      arthroplasty offers potential advantages for optimizing the hip center of
      rotation, it has been associated with modular taper corrosion. This corrosion has
      led to adverse local tissue reactions (pseudotumors) at the neck-stem junction
      and elevated metal-ion levels. However, the occurrence of taper-corrosion-related
      pseudotumors in patients who remain asymptomatic following total hip arthroplasty
      with a dual-taper modular femoral stem remains largely unknown. The aims of this
      study were (1) to determine the prevalence of asymptomatic pseudotumors by
      utilizing metal artifact reduction sequence magnetic resonance imaging (MARS-MRI)
      and (2) compare serum metal-ion levels between symptomatic and asymptomatic
      patients with a dual-taper modular stem total hip replacement. METHODS: We
      performed a retrospective cross-sectional study of 97 consecutive patients who
      had been treated with a dual-taper modular femoral stem total hip arthroplasty.
      Eighty-three patients were stratified into symptomatic and asymptomatic groups
      and evaluated with MARS-MRI, measurement of serum metal-ion levels, and the
      University of California at Los Angeles (UCLA) functional hip score. RESULTS: The
      prevalence of pseudotumors as determined with MARS-MRI was 15% in our
      asymptomatic patients and 36% in the overall cohort. The median serum cobalt
      level and cobalt/chromium ratio were significantly higher in patients with a
      pseudotumor than in those without a pseudotumor (8.0 versus 2.0 MUg/L [p = 0.004]
      and 10.3 versus 2.4 MUg/L [p = 0.012], respectively). However, there was no
      significant difference in the serum cobalt level or cobalt/chromium ratio between
      symptomatic patients with a pseudotumor and asymptomatic patients with a
      pseudotumor (7.6 versus 6.2 MUg/L [p = 0.37] and 8.3 versus 10.6 MUg/L [p =
      0.46], respectively). The UCLA scores of asymptomatic patients with a pseudotumor
      were similar to those of patients without a pseudotumor (6.7 versus 6.6).
      CONCLUSIONS: The prevalence of asymptomatic taper-corrosion-related pseudotumors
      on MARS-MRI in this study demonstrated that the absence of symptoms does not
      exclude the presence of adverse local tissue reactions. Elevated cobalt levels
      and cobalt/chromium ratios were associated with the presence of pseudotumors in
      asymptomatic and symptomatic patients. Cross-sectional imaging such as MARS-MRI
      is indicated for patients with elevated metal-ion levels. A longitudinal study is
      required to determine whether asymptomatic patients with taper-corrosion-related
      pseudotumors will develop symptoms with time. LEVEL OF EVIDENCE: Therapeutic
      Level IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 27869626
TI  - Primary Linked Semiconstrained Total Elbow Arthroplasty for Rheumatoid Arthritis:
      A Single-Institution Experience with 461 Elbows Over Three Decades.
AB  - BACKGROUND: Elbow arthroplasty is the treatment of choice for end-stage
      rheumatoid arthritis (RA). The purpose of this study was to determine the long
      term outcome of a linked semiconstrained elbow arthroplasty implant design in
      patients with RA. METHODS: Between 1982 and 2006, 461 primary total elbow
      arthroplasties using the Coonrad-Morrey prosthesis were performed in 387 patients
      with RA. Fifty-five of the arthroplasties were performed to treat concurrent
      traumatic or posttraumatic conditions. There were 305 women (365 elbows, 79%) and
      82 men (96 elbows, 21%). Ten patients (10 elbows) were lost to follow-up, 9
      patients (10 elbows) died, and 6 patients (6 elbows) underwent revision surgery
      within the first 2 years. For the 435 elbows (362 patients, 94%) with a minimum
      of 2 years of follow-up, the median follow-up was 10 years (range, 2 to 30
      years). RESULTS: At the most recent follow-up, 49 (11%) of the elbows had
      undergone component revision or removal (deep infection, 10 elbows; and
      mechanical failure, 39 elbows). Eight additional elbows were considered to have
      radiographic evidence of loosening. For surviving implants followed for a minimum
      of 2 years, the median Mayo Elbow Performance Score (MEPS) was 90 points. Bushing
      wear was identified in 71 (23%) of the surviving elbows with a minimum of 2 years
      of radiographic follow-up; however, only 2% of the elbows had been revised for
      isolated bushing wear. The rate of survivorship free of implant revision or
      removal for any reason was 92% (95% confidence interval [CI] = 88% to 94%) at 10
      years, 83% (95% CI = 77% to 88%) at 15 years, and 68% (95% CI = 56% to 78%) at 20
      years. The survivorship at 20 years was 88% (95% CI = 83% to 92%) with revision
      due to aseptic loosening as the end point and 89% (95% CI = 77% to 95%) with
      isolated bushing exchange as the end point. Risk factors for implant revision for
      any cause included male sex, a history of concomitant traumatic pathology, and
      implantation of an ulnar component with a polymethylmethacrylate surface finish.
      CONCLUSIONS: Elbow arthroplasty using a cemented linked semiconstrained elbow
      arthroplasty provides satisfactory clinical results in the treatment of RA with a
      reasonable rate of survivorship free of mechanical failure at 20 years. Although
      bushing wear was identified on radiographs in approximately one-fourth of the
      patients, revision for isolated bushing wear was uncommon. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 27869627
TI  - The American Academy of Orthopaedic Surgeons Evidence-Based Clinical Practice
      Guideline on: Management of Carpal Tunnel Syndrome.

PMID- 27869628
TI  - What's New in Shoulder and Elbow Surgery.

PMID- 27869629
TI  - Coagulation Profile of Patients with Adolescent Idiopathic Scoliosis Undergoing
      Posterior Spinal Fusion.
AB  - BACKGROUND: Blood loss and transfusion requirements during posterior spinal
      fusion for adolescent idiopathic scoliosis remain a concern. The mechanism of
      bleeding in these patients is poorly characterized. Thromboelastography is a
      comprehensive test of a patient's coagulation system commonly used in cardiac
      surgical procedures. It has not been well studied for use in patients with
      adolescent idiopathic scoliosis. METHODS: A prospective, observational study of
      the coagulation profile of patients with adolescent idiopathic scoliosis
      undergoing posterior spinal fusion is presented. Healthy patients with adolescent
      idiopathic scoliosis without a bleeding abnormality were analyzed during
      posterior spinal fusion. Standard coagulation laboratory and thromboelastogram
      measures were obtained at the time of the incision and at 1-hour intervals during
      the surgical procedure. Laboratory values were analyzed in relation to outcomes
      such as bleeding, transfusion, and a fibrinolysis score. RESULTS: Fifty-eight
      patients were observed. Eighty-one percent of patients were female, the mean age
      was 13.5 years, a mean of 11.1 levels were fused, the median estimated blood loss
      was 645 mL, and 47% of patients received blood products. Overall, laboratory
      values remained stable throughout the surgical procedure. Mild increases in
      prothrombin time and partial thromboplastin time were observed, and platelets
      remained stable. From thromboelastogram analysis, an acceleration of clot
      formation (decreased reaction time) and a slight increase in clot lysis
      (increased lysis percentage at 30 minutes) were observed. A fibrinolysis score
      compiled from the presence of fibrin degradation products, the presence of D
      dimers, and increased prothrombin time rose steadily over surgical time. The
      fibrinolysis score was predictive of both transfusion and greater estimated blood
      loss per level. CONCLUSIONS: The stress of posterior spinal fusion induces a
      hypercoagulable state in patients with adolescent idiopathic scoliosis. Over the
      first 2 hours of a surgical procedure, varying degrees of fibrinolysis develop.
      Platelets and coagulation factors are not depleted. Our data support the use of
      antifibrinolytic therapy for patients with adolescent idiopathic scoliosis.

PMID- 27869631
TI  - Inconsistencies Between Physician-Reported Disclosures at the AAOS Annual Meeting
      and Industry-Reported Financial Disclosures in the Open Payments Database.
AB  - BACKGROUND: The purpose of this study was to determine the rate and type of
      inconsistencies between disclosures self-reported by physicians at a major
      academic meeting in the United States and industry-reported disclosures in the
      Open Payments database for a concordant time period. METHODS: Disclosures for
      every first and last author from the United States with a medical degree of a
      podium or poster presentation at the 2014 American Academy of Orthopaedic
      Surgeons (AAOS) Annual Meeting were collected and were compared with the
      disclosures reported in the Open Payments database to determine if any
      inconsistencies were present and, if so, within which category. RESULTS: In
      total, 1,925 total AAOS presenters were identified, and 1,113 met the inclusion
      criteria. Based on AAOS disclosures, 432 (39%) should have been listed within the
      Open Payments database. There were 125 presenters (11%) who reported an AAOS
      disclosure and thus should have been included in the Open Payments database, but
      were not included. An additional 259 presenters (23%) had >=1 AAOS disclosures
      that were not reported or were improperly categorized in the Open Payments
      database. Inconsistencies were more common for authors who had significantly more
      poster presentations (p < 0.001), podium presentations (p = 0.01), total
      presentations (p < 0.001), and AAOS disclosures (p < 0.001) and a significantly
      higher value of payments in the Open Payments database (p < 0.001). CONCLUSIONS:
      In this sample, there was a 35% rate of inconsistency between physician-reported
      financial relationships for presenters at the AAOS Annual Meeting and industry
      reported relationships published in the Open Payments database.

PMID- 27869630
TI  - A Prospective Evaluation of Opioid Utilization After Upper-Extremity Surgical
      Procedures: Identifying Consumption Patterns and Determining Prescribing
      Guidelines.
AB  - BACKGROUND: Although adequate management of postoperative pain with oral
      analgesics is an important aspect of surgical procedures, inadvertent
      overprescribing can lead to excess availability of opioids in the community for
      potential diversion. The purpose of our study was to prospectively evaluate
      opioid consumption following outpatient upper-extremity surgical procedures to
      determine opioid utilization patterns and to develop prescribing guidelines.
      METHODS: All patients undergoing outpatient upper-extremity surgical procedures
      over a consecutive 6-month period had the following prospective data collected:
      patient demographic characteristics, surgical details, anesthesia type, and
      opioid prescription and consumption patterns. Analysis of variance and post hoc
      comparisons were performed using t tests, with the p value for multiple pairwise
      tests adjusted by the Bonferroni correction. RESULTS: A total of 1,416 patients
      with a mean age of 56 years (range, 18 to 93 years) were included in the study.
      Surgeons prescribed a mean total of 24 pills, and patients reported consuming a
      mean total of 8.1 pills, resulting in a utilization rate of 34%. Patients
      undergoing soft-tissue procedures reported requiring fewer opioids (5.1 pills for
      2.2 days) compared with fracture surgical procedures (13.0 pills for 4.5 days) or
      joint procedures (14.5 pills for 5.0 days) (p < 0.001). Patients who underwent
      wrist surgical procedures required a mean number of 7.5 pills for 3.1 days and
      those who underwent hand surgical procedures required a mean number of 7.7 pills
      for 2.9 days, compared with patients who underwent forearm or elbow surgical
      procedures (11.1 pills) and those who underwent upper arm or shoulder surgical
      procedures (22.0 pills) (p < 0.01). Procedure type, anatomic location, anesthesia
      type, age, and type of insurance were also all significantly associated with
      reported opioid consumption (p < 0.001). CONCLUSIONS: In this large, prospective
      evaluation of postoperative opioid consumption, we found that patients are being
      prescribed approximately 3 times greater opioid medications than needed following
      upper-extremity surgical procedures. We have provided general prescribing
      guidelines, and we recommend that surgeons carefully examine their patients'
      opioid utilization and consider customizing their opioid prescriptions on the
      basis of anatomic location and procedure type to prescribe the optimal amount of
      opioids while avoiding dissemination of excess opioids.

PMID- 27869632
TI  - P-Hacking in Orthopaedic Literature: A Twist to the Tail.
AB  - BACKGROUND: "P-hacking" occurs when researchers preferentially select data or
      statistical analyses until nonsignificant results become significant. We wanted
      to evaluate if the phenomenon of p-hacking was evident in orthopaedic literature.
      METHODS: We text-mined through all articles published in three top orthopaedic
      journals in 2015. For anonymity, we cipher-coded the three journals. We included
      all studies that reported a single p value to answer their main hypothesis. These
      p values were then charted and frequency graphs were generated to illustrate any
      evidence of p-hacking. Binomial tests were employed to look for evidence of
      evidential value and significance of p-hacking. RESULTS: Frequency plots for all
      three journals revealed evidence of p-hacking. Binomial tests for all three
      journals were significant for evidence of evidential value (p < 0.0001 for all).
      However, the binomial test for p-hacking was significant only for one journal (p
      = 0.0092). CONCLUSIONS: P-hacking is an evolving phenomenon that threatens to
      jeopardize the evidence-based practice of medicine. Although our results show
      that there is good evidential value for orthopaedic literature published in our
      top journals, there is some evidence of p-hacking of which authors and readers
      should be wary.

PMID- 27869633
TI  - Should Only the Highest-Volume Surgeons and Centers Be Doing Primary Total Knee
      Arthroplasty? Commentary on an article by Sean Wilson, BA, et al.: "Meaningful
      Thresholds for the Volume-Outcome Relationship in Total Knee Arthroplasty".

PMID- 27869635
TI  - Erratum.

PMID- 27869634
TI  - Goals and Challenges of Identifying Asymptomatic Pseudotumors in Patients Treated
      with Total Hip Arthroplasty: Commentary on an article by Young-Min Kwon, MD, PhD,
      et al.: "Asymptomatic Pseudotumors in Patients with Taper Corrosion of a Dual
      Taper Modular Femoral Stem: MARS-MRI and Metal Ion Study".

PMID- 27869636
TI  - Insignificant influence of the matrix on the melting of incoherently embedded tin
      and zinc nanoparticles.
AB  - For studying the melting point depression of metals, isolated metallic
      nanoparticles embedded in a matrix are usually prepared by mechanical milling. Al
      is the main available matrix material. In this work, to explore possible
      alternative matrices for further investigation of melting, mechanically milled
      metal-nonmetal systems are developed, namely Sn-LiF, Zn-LiF and Zn-Al2O3. The
      outcome indicates that different matrices do not have a significantly different
      influence on the melting of Sn and Zn. Theoretical analyses of both the
      thermodynamics and kinetics of surface-induced melting may support this
      experimental finding.

PMID- 27869637
TI  - The lattice stiffening transition in UO2 single crystals.
AB  - The effective Debye temperatures ([Formula: see text]) of the surface region of
      UO2 single crystals, prepared by the hydrothermal synthesis technique, were
      obtained from temperature-dependent x-ray photoemission in the temperature range
      of 300 K-623 K. A lattice stiffening transition, characterized by different
      regions of different effective Debye temperature, 500  +/-  59 K below 475 K and
      165  +/-  21 K above 475 K is identified. A comparison of the temperature
      dependence of the effective UO2 Debye temperature, with the changes in the
      lattice expansion coefficient for UO2, support strong lattice-phonon interaction
      arising from the Jahn-Teller distortion.

PMID- 27869638
TI  - A realistic quantum capacitance model for quantum Hall edge state based Fabry
      Perot interferometers.
AB  - In this work, the classical and the quantum capacitances are calculated for a
      Fabry-Perot interferometer operating in the integer quantized Hall regime. We
      first consider a rotationally symmetric electrostatic confinement potential and
      obtain the widths and the spatial distribution of the insulating (incompressible)
      circular strips using a charge density profile stemming from self-consistent
      calculations. Modelling the electrical circuit of capacitors composed of metallic
      gates and incompressible/compressible strips, we investigate the conditions to
      observe Aharonov-Bohm (quantum mechanical phase dependent) and Coulomb blockade
      (capacitive coupling dependent) effects reflected in conductance oscillations. In
      a last step, we solve the Schrodinger and the Poisson equations self-consistently
      in a numerical manner taking into account realistic experimental geometries. We
      find that, describing the conductance oscillations either by Aharanov-Bohm or
      Coulomb blockade strongly depends on sample properties also other than size,
      therefore, determining the origin of these oscillations requires further
      experimental and theoretical investigation.

PMID- 27869639
TI  - Thermal response in van der Waals heterostructures.
AB  - We solve numerically the Boltzmann transport equations of the phonons and
      electrons to understand the thermoelectric response in heterostructures of M2CO2
      (M: Ti, Zr, Hf) MXenes with transition metal dichalcogenide monolayers. Low
      frequency optical phonons are found to occur as a consequence of the van der
      Waals bonding, contribute significantly to the thermal transport, and compensate
      for the reduced contributions of the acoustic phonons (increased scattering cross
      sections in heterostructures), such that the thermal conductivities turn out to
      be similar to those of the bare MXenes. Our results indicate that the important
      superlattice design approach of thermoelectrics (to reduce the thermal
      conductivity) may be effective for two-dimensional van der Waals materials when
      used in conjunction with intercalation.

PMID- 27869640
TI  - Flexible anodized aluminum oxide membranes with customizable back contact
      materials.
AB  - Anodized aluminum oxide (AAO) membranes were fabricated using flexible
      substrate/carrier material. This method facilitates the use of AAO templates with
      many different materials as substrates that are otherwise incompatible with most
      anodization techniques. Thin titanium (Ti) and tungsten (W) layers were employed
      as interlayer materials. Titanium enhances adhesion. Tungsten not only helps
      eliminate the barrier layer but also plays a critical role in enabling the use of
      flexible substrates. The resulting flexible templates provide new, exciting
      opportunities in photovoltaic and other device applications. CuInSe2 nanowires
      were electrochemically deposited into porous AAO templates with molybdenum (Mo)
      as the back contact material. The feasibility of using any material to form a
      contact with semiconductor nanowires has been demonstrated for the first time
      enabling new avenues in photovoltaic applications.

PMID- 27869641
TI  - Orbital breathing effects in the computation of x-ray d-ion spectra in solids by
      ab initio wave-function-based methods.
AB  - In existing theoretical approaches to core-level excitations of transition-metal
      ions in solids relaxation and polarization effects due to the inner core hole are
      often ignored or described phenomenologically. Here we set up an ab initio
      computational scheme that explicitly accounts for such physics in the calculation
      of x-ray absorption and resonant inelastic x-ray scattering spectra. Good
      agreement is found with experimental transition-metal L-edge data for the
      strongly correlated d 9 cuprate Li2CuO2, for which we determine the absolute
      scattering intensities. The newly developed methodology opens the way for the
      investigation of even more complex d n electronic structures of group VI B to
      VIII B correlated oxide compounds.

PMID- 27869642
TI  - Metal-free N-doped carbon nanofibers as an efficient catalyst for oxygen
      reduction reactions in alkaline and acid media.
AB  - The development of metal-free catalysts to replace the use of Pt has played an
      important role in relation to its application to fuel cells. We report N-doped
      carbon nanofibers as the catalyst of an oxygen reduction reaction, which were
      synthesized via carbonizing bacterial cellulose-polypyrrole composites. The as
      prepared material exhibited remarkable catalytic activity toward the oxygen
      reduction reaction with comparable onset potential and the ability to limit the
      current density of commercial Pt/C catalysts in both alkaline and acid media due
      to the unique porous three-dimensional network structure and the doped nitrogen
      atoms. The effect of N functionalities on catalytic behavior was systematically
      investigated. The results demonstrated that pyridinic-N was the dominating factor
      for catalytic performance toward the oxygen reduction reaction. Additionally, N
      doped carbon nanofibers also demonstrated excellent cycling stability (93.2% and
      89.4% retention of current density after chronoamperometry 20 000 s in alkaline
      and media, respectively), obviously superior to Pt/C.

PMID- 27869643
TI  - First-principles calculations of momentum distributions of annihilating electron
      positron pairs in defects in UO2.
AB  - We performed first-principles calculations of the momentum distributions of
      annihilating electron-positron pairs in vacancies in uranium dioxide. Full atomic
      relaxation effects (due to both electronic and positronic forces) were taken into
      account and self-consistent two-component density functional theory schemes were
      used. We present one-dimensional momentum distributions (Doppler-broadened
      annihilation radiation line shapes) along with line-shape parameters S and W. We
      studied the effect of the charge state of the defect on the Doppler spectra. The
      effect of krypton incorporation in the vacancy was also considered and it was
      shown that it should be possible to observe the fission gas incorporation in
      defects in UO2 using positron annihilation spectroscopy. We suggest that the
      Doppler broadening measurements can be especially useful for studying impurities
      and dopants in UO2 and of mixed actinide oxides.

PMID- 27869644
TI  - Hydrogen gas sensors from polysilicon nanobelt devices selectively modified with
      sensing materials.
AB  - Double-junction n+/n-/n+ polysilicon nanobelts featuring selectively deposited
      sensing materials have been investigated for application as H2 gas sensors. The
      selective modification of the devices was performed through a combination of
      localized ablation of a resist and lift-off of a previous catalyst material
      deposited through e-beam evaporation. Four nanobelt devices, differentiated by
      their doping concentrations at the n- region (from 2.5 * 1013 to 2.5 * 1014 cm
      2), were analyzed in terms of the responses to H2 and their self-heating effects.
      A low doping concentration improved the response at room temperature, owing to a
      longer Debye length. The variation in the H2-induced surface potential associated
      with temperature, accounting for degradation in the response of the nanobelts
      with Joule heating bias, was analyzed in terms of the I-V characteristics of the
      double-junction device. Among various catalysts (Pt, Pd, Pt/Pd) evaluated for
      their H2 sensing characteristics, an ultrathin film of Pt/Pd was most favorable.

PMID- 27869646
TI  - Magnetoelectric effects in the spiral magnets CuCl2 and CuBr2.
AB  - The nature and symmetry of transition mechanisms in the spin-spiral copper
      halides CuCl2 and CuBr2 are analyzed theoretically. The magnetoelectric effects
      observed in the two multiferroic compounds are described and their phase diagram
      at zero and applied magnetic fields are worked out. The emergence of the electric
      polarization at zero field below the paramagnetic phase is shown to result from
      the coupling of two distinct spin-density waves and to be only partly related to
      the Dzialoshinskii-Moriya interactions. Applying a magnetic field along the two
      fold monoclinic axis of CuCl2 yields a decoupling of the spin-density waves
      modifying the symmetry of the phase and the spin-spiral orientation. The
      remarkable periodic dependences of the magnetic susceptibility and polarization,
      on rotating the field in the monoclinic plane, are described theoretically.

PMID- 27869645
TI  - Size effect on high temperature variable range hopping in Al+ implanted 4H-SiC.
AB  - The hole transport properties of heavily doped 4H-SiC (Al) layers with Al
      implanted concentrations of 3  *  1020 and 5  *  1020 cm-3 and annealed in the
      temperature range 1950-2100  degrees C, have been analyzed to determine the main
      transport mechanisms. This study shows that the temperature dependence of the
      resistivity (conductivity) may be accounted for by a variable range hopping (VRH)
      transport into an impurity band. Depending on the concentration of the implanted
      impurities and the post-implantation annealing treatment, this VRH mechanism
      persists over different temperature ranges that may extend up to room
      temperature. In this framework, two different transport regimes are identified,
      having the characteristic of an isotropic 3D VRH and an anisotropic nearly 2D
      VRH. The latter conduction mechanism appears to take place in a rather thick
      layer (about 400 nm) that is too large to induce a confinement effect of the
      carrier hops. The possibility that an anisotropic transport may be induced by a
      structural modification of the implanted layer because of a high density of basal
      plane stacking faults (SF) in the implanted layers is considered. The
      interpretation of the conduction in the heaviest doped samples in terms of nearly
      2D VRH is supported by the results of the transmission electron microscopy (TEM)
      investigation on one of the 5  *  1020 cm-3 Al implanted samples of this study.
      In this context, the average separation between basal plane SFs, measured along
      the c-axis, which is orthogonal to the carrier transport during electrical
      characterization, appears to be in keeping with the estimated value of the
      optimal hopping length of the VRH theory. Conversely, no SFs are detected by TEM
      in a sample with an Al concentration of 1  *  1019 cm-3 where a 3D nearest
      neighbor hopping (NNH) transport is observed.

PMID- 27869647
TI  - Temperature measurement of Joule heated silicon micro/nanowires using selectively
      decorated quantum dots.
AB  - We developed a novel method to measure local temperature at micro/nano-scale
      regions using selective deposition of quantum dots (QDs) as a sensitive
      temperature probe and measured the temperature of Joule heated silicon microwires
      (SiMWs) and silicon nanowires (SiNWs) by this method. The QDs are selectively
      coated only on the surface of the SiMWs and SiNWs by a sequential process
      composed of selective opening of a polymethyl methacrylate layer via Joule
      heating, covalent bonding of QDs, and lift-off process. The temperatures of the
      Joule-heated SiMWs and SiNWs can be measured by characterizing the temperature
      dependent shift of photoluminescence peak of the selectively deposited QDs even
      with far-field optics. The validity of the extracted temperature has been also
      confirmed by comparing with numerical simulation results. The proposed method can
      potentially provide micro/nanoscale measurement of localized temperatures for a
      wide range of electrical and optical devices.

PMID- 27869648
TI  - Hippo signaling interactions with Wnt/beta-catenin and Notch signaling repress
      liver tumorigenesis.
AB  - Malignant tumors develop through multiple steps of initiation and progression,
      and tumor initiation is of singular importance in tumor prevention, diagnosis,
      and treatment. However, the molecular mechanism whereby a signaling network of
      interacting pathways restrains proliferation in normal cells and prevents tumor
      initiation is still poorly understood. Here, we have reported that the Hippo,
      Wnt/beta-catenin, and Notch pathways form an interacting network to maintain
      liver size and suppress hepatocellular carcinoma (HCC). Ablation of the mammalian
      Hippo kinases Mst1 and Mst2 in liver led to rapid HCC formation and activated Yes
      associated protein/WW domain containing transcription regulator 1 (YAP/TAZ),
      STAT3, Wnt/beta-catenin, and Notch signaling. Previous work has shown that
      abnormal activation of these downstream pathways can lead to HCC. Rigorous
      genetic experiments revealed that Notch signaling forms a positive feedback loop
      with the Hippo signaling effector YAP/TAZ to promote severe hepatomegaly and
      rapid HCC initiation and progression. Surprisingly, we found that Wnt/beta
      catenin signaling activation suppressed HCC formation by inhibiting the positive
      feedback loop between YAP/TAZ and Notch signaling. Furthermore, we found that
      STAT3 in hepatocytes is dispensable for HCC formation when mammalian sterile 20
      like kinase 1 and 2 (Mst1 and Mst2) were removed. The molecular network we have
      identified provides insights into HCC molecular classifications and therapeutic
      developments for the treatment of liver tumors caused by distinct genetic
      mutations.

PMID- 27869649
TI  - Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer
      precursor immunotherapy.
AB  - BACKGROUND: Actinic keratosis is a precursor to cutaneous squamous cell
      carcinoma. Long treatment durations and severe side effects have limited the
      efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin
      (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity
      in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a
      topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an
      immunotherapy for actinic keratosis. METHODS: The mechanism of calcipotriol
      action against skin carcinogenesis was examined in genetically engineered mouse
      models. The efficacy and safety of 0.005% calcipotriol ointment combined with 5%
      5-FU cream were compared with Vaseline plus 5-FU for the field treatment of
      actinic keratosis in a randomized, double-blind clinical trial involving 131
      participants. The assigned treatment was self-applied to the entirety of the
      qualified anatomical sites (face, scalp, and upper extremities) twice daily for 4
      consecutive days. The percentage of reduction in the number of actinic keratoses
      (primary outcome), local skin reactions, and immune activation parameters were
      assessed. RESULTS: Calcipotriol suppressed skin cancer development in mice in a
      TSLP-dependent manner. Four-day application of calcipotriol plus 5-FU versus
      Vaseline plus 5-FU led to an 87.8% versus 26.3% mean reduction in the number of
      actinic keratoses in participants (P < 0.0001). Importantly, calcipotriol plus 5
      FU treatment induced TSLP, HLA class II, and natural killer cell group 2D (NKG2D)
      ligand expression in the lesional keratinocytes associated with a marked CD4+ T
      cell infiltration, which peaked on days 10-11 after treatment, without pain,
      crusting, or ulceration. CONCLUSION: Our findings demonstrate the synergistic
      effects of calcipotriol and 5-FU treatment in optimally activating a CD4+ T cell
      mediated immunity against actinic keratoses and, potentially, cancers of the skin
      and other organs. TRIAL REGISTRATION: ClinicalTrials.gov NCT02019355. FUNDING:
      Not applicable (investigator-initiated clinical trial).

PMID- 27869650
TI  - Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li
      Fraumeni syndrome.
AB  - Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder caused by germline
      mutations in TP53 that can lead to increased mitochondrial metabolism in
      patients. However, the implications of altered mitochondrial function for
      tumorigenesis in LFS are unclear. Here, we have reported that genetic or
      pharmacologic disruption of mitochondrial respiration improves cancer-free
      survival in a mouse model of LFS that expresses mutant p53. Mechanistically,
      inhibition of mitochondrial function increased autophagy and decreased the
      aberrant proliferation signaling caused by mutant p53. In a pilot study, LFS
      patients treated with metformin exhibited decreases in mitochondrial activity
      concomitant with activation of antiproliferation signaling, thus reproducing the
      effects of disrupting mitochondrial function observed in LFS mice. These
      observations indicate that a commonly prescribed diabetic medicine can restrain
      mitochondrial metabolism and tumorigenesis in an LFS model, supporting its
      further consideration for cancer prevention in LFS patients.

PMID- 27869651
TI  - Pericyte MyD88 and IRAK4 control inflammatory and fibrotic responses to tissue
      injury.
AB  - Fibrotic disease is associated with matrix deposition that results in the loss of
      organ function. Pericytes, the precursors of myofibroblasts, are a source of
      pathological matrix collagens and may be promising targets for treating
      fibrogenesis. Here, we have shown that pericytes activate a TLR2/4- and MyD88
      dependent proinflammatory program in response to tissue injury. Similarly to
      classic immune cells, pericytes activate the NLRP3 inflammasome, leading to IL
      1beta and IL-18 secretion. Released IL-1beta signals through pericyte MyD88 to
      amplify this response. Unexpectedly, we found that MyD88 and its downstream
      effector kinase IRAK4 intrinsically control pericyte migration and conversion to
      myofibroblasts. Specific ablation of MyD88 in pericytes or pharmacological
      inhibition of MyD88 signaling by an IRAK4 inhibitor in vivo protected against
      kidney injury by profoundly attenuating tissue injury, activation, and
      differentiation of myofibroblasts. Our data show that in pericytes, MyD88 and
      IRAK4 are key regulators of 2 major injury responses: inflammatory and
      fibrogenic. Moreover, these findings suggest that disruption of this MyD88
      dependent pathway in pericytes might be a potential therapeutic approach to
      inhibit fibrogenesis and promote regeneration.

PMID- 27869653
TI  - Semiparametric Multinomial Ordinal Model to Analyze Spatial Patterns of Child
      Birth Weight in Nigeria.
AB  - Background: Birth weight is an important health parameter for obstetricians and
      gynaecologists. It is a good health indicator of a child-bearing mother and a
      strong predictor of infant morbidity and mortality. Methods: This paper utilizes
      data on 28,647 children born between 2003-2008 obtained from the 2008 Nigeria
      Demographic and Health Survey (NDHS). For a simple epidemiological convenience,
      the occurrence of a newborn weight can intuitively be considered to be
      categorical in nature and the thresholds can be put on a continuous scale. In
      survey reporting, the mothers frequently estimate their infant's birth weight and
      make a classification in ordinal category (low, normal, large) instead of actual
      birth weight. The study fits a multinomial regression model to analyze the
      relationships between the polytomous response and different kind of covariates in
      a unified manner. We estimate the fixed effects of bio-social covariates
      parametrically and the non-linear effect modeled using P-spline. The spatial
      component was modeled using conditional autoregressive error. A penalized maximum
      likelihood estimation was performed to estimate the model parameters. Results: We
      found risk factors that are positively associated with low birth weight, which
      include multiple birth, short birth interval, death of sibling, childhood
      diarrhea, fever, mother's smoking, firewood/dung cooking and poor household.
      Results further showed that iron syrup supplementation, antenatal attendance,
      mother literacy and household wealth had significant association with low
      probability of low birth weight. The finding also showed spatial patterns, which
      are not captured by the underlying determinants, and we produced probability
      predictive maps of the spatial residual effects. Conclusions: In addition to the
      statistical relevance of our method, the generated spatial maps identify highly
      endemic areas of low birth weight that can assist government agency to channel
      scarce health resources. A comprehensive approach which institutes a combination
      of interventions to improve the overall health care of the women is needed.

PMID- 27869655
TI  - A Shared Decision-Making Approach to Telemedicine: Engaging Rural Patients in
      Glycemic Management.
AB  - Telemedicine can connect specialist health care providers with patients in remote
      and underserved areas. It is especially relevant in diabetes care, where a
      proliferation of treatment options has added further complexity to the care of an
      already complex, highly prevalent disease. Recent developments in health reform
      encourage delivery systems to use team-based models and engage patients in shared
      decision-making (SDM), where patients and providers together make health care
      decisions that are tailored to the specific characteristics and values of the
      patient. The goal of this project was to design, integrate, and evaluate a team
      based, SDM approach delivered to patients with diabetes in a rural community,
      building upon the previously established telemedicine for reach, education,
      access, and treatment (TREAT) model. Patients in this feasibility study
      demonstrated improvement in hemoglobin A1c values, and reported better
      understanding of diabetes. Providers reported the SDM aids increased cohesion
      among team members (including patients) and facilitated patient education and
      behavioral goal setting. This project demonstrated that SDM could be integrated
      into the workflow of a telemedicine team visit with good provider and patient
      satisfaction.

PMID- 27869652
TI  - Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction
      process through scaffolding protein PAQR11.
AB  - Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent
      (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and
      transport of secretory vesicles. Whether Golgi dispersal underlies the pro
      metastatic vesicular trafficking that is associated with epithelial-to
      mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather
      than causing Golgi dispersal, EMT led to the formation of compact Golgi
      organelles with improved ribbon linking and cisternal stacking. Ectopic
      expression of the EMT-activating transcription factor ZEB1 stimulated Golgi
      compaction and relieved microRNA-mediated repression of the Golgi scaffolding
      protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired
      anterograde vesicle transport to the plasma membrane as well as retrograde
      vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was
      associated with key regulators of Golgi compaction and vesicle transport in pull
      down assays and was required to reconstitute Golgi compaction in PAQR11-deficient
      tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter
      survival in human cancers, and PAQR11 was found to be essential for tumor cell
      migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude
      that EMT initiates a PAQR11-mediated Golgi compaction process that drives
      metastasis.

PMID- 27869654
TI  - The Safety Attitudes of Senior Managers in the Chinese Coal Industry.
AB  - Introduction: Senior managers' attitudes towards safety are very important
      regarding the safety practices in an organization. The study is to describe the
      current situation of senior managers' attitudes towards safety in the Chinese
      coal industry. Method: We evaluated the changing trends as well as the reasons
      for these changes in the Chinese coal industry in 2009 and in 2014 with 168
      senior manager samples from large Chinese state-owned coal enterprises.
      Evaluations of 15 safety concepts were performed by means of a questionnaire.
      Results and Conclusions: Results indicate that, in 2014, three concepts were at a
      very high level (mean > 4.5), and six were at a relatively high level (4.5 > mean
      > 4.0). Analyses of changing trends revealed that nine concepts improved
      significantly, while four greatly declined in 2014 compared to those in 2009. The
      data reported here suggest that the reasons for the significant improvement with
      respect to the nine concepts include the improvement in social and legal
      environments, the improvement of the culture of social safety, workers' safety
      demands being met, and scientific and technical advances in the coal industry.
      The decline of the four concepts seemed to be caused by a poor awareness of
      managers in the coal industry that safety creates economic benefits, insufficient
      information on safety, inadequate attention to the development of a safety
      culture and safety management methods, and safety organizations and workers'
      unions not playing their role effectively. Practical Applications: We therefore
      recommend strengthening the evidence that safety creates economic benefits,
      providing incentives for employees to encourage their participation in safety
      management, and paying more attention to the prevention of accidents in coal
      mines via safety organizations and unions. These results can provide guidelines
      for workers, industrialists, and government regarding occupational safety in the
      whole coal industry.

PMID- 27869656
TI  - Approach for Self-Calibrating CO2 Measurements with Linear Membrane-Based Gas
      Sensors.
AB  - Linear membrane-based gas sensors that can be advantageously applied for the
      measurement of a single gas component in large heterogeneous systems, e.g., for
      representative determination of CO2 in the subsurface, can be designed depending
      on the properties of the observation object. A resulting disadvantage is that the
      permeation-based sensor response depends on operating conditions, the individual
      site-adapted sensor geometry, the membrane material, and the target gas
      component. Therefore, calibration is needed, especially of the slope, which could
      change over several orders of magnitude. A calibration-free approach based on an
      internal gas standard is developed to overcome the multi-criterial slope
      dependency. This results in a normalization of sensor response and enables the
      sensor to assess the significance of measurement. The approach was proofed on the
      example of CO2 analysis in dry air with tubular PDMS membranes for various CO2
      concentrations of an internal standard. Negligible temperature dependency was
      found within an 18 K range. The transformation behavior of the measurement signal
      and the influence of concentration variations of the internal standard on the
      measurement signal were shown. Offsets that were adjusted based on the stated
      theory for the given measurement conditions and material data from the literature
      were in agreement with the experimentally determined offsets. A measurement
      comparison with an NDIR reference sensor shows an unexpectedly low bias (<1%) of
      the non-calibrated sensor response, and comparable statistical uncertainty.

PMID- 27869657
TI  - Real-Time Lane Region Detection Using a Combination of Geometrical and Image
      Features.
AB  - Over the past few decades, pavement markings have played a key role in
      intelligent vehicle applications such as guidance, navigation, and control.
      However, there are still serious issues facing the problem of lane marking
      detection. For example, problems include excessive processing time and false
      detection due to similarities in color and edges between traffic signs
      (channeling lines, stop lines, crosswalk, arrows, etc.). This paper proposes a
      strategy to extract the lane marking information taking into consideration its
      features such as color, edge, and width, as well as the vehicle speed. Firstly,
      defining the region of interest is a critical task to achieve real-time
      performance. In this sense, the region of interest is dependent on vehicle speed.
      Secondly, the lane markings are detected by using a hybrid color-edge feature
      method along with a probabilistic method, based on distance-color dependence and
      a hierarchical fitting model. Thirdly, the following lane marking information is
      extracted: the number of lane markings to both sides of the vehicle, the
      respective fitting model, and the centroid information of the lane. Using these
      parameters, the region is computed by using a road geometric model. To evaluate
      the proposed method, a set of consecutive frames was used in order to validate
      the performance.

PMID- 27869659
TI  - Full-Field Optical Coherence Tomography Using Galvo Filter-Based Wavelength Swept
      Laser.
AB  - We report a wavelength swept laser-based full-field optical coherence tomography
      for measuring the surfaces and thicknesses of refractive and reflective samples.
      The system consists of a galvo filter-based wavelength swept laser and a simple
      Michelson interferometer. Combinations of the reflective and refractive samples
      are used to demonstrate the performance of the system. By synchronizing the
      camera with the source, the cross-sectional information of the samples can be
      seen after each sweep of the swept source. This system can be effective for the
      thickness measurement of optical thin films as well as for the depth
      investigation of samples in industrial applications. A resolution target with a
      glass cover slip and a step height standard target are imaged, showing the cross
      sectional and topographical information of the samples.

PMID- 27869660
TI  - Use of a Fluorescent Aptamer RNA as an Exonic Sequence to Analyze Self-Splicing
      Ability of aGroup I Intron from Structured RNAs.
AB  - Group I self-splicing intron constitutes an important class of functional RNA
      molecules that can promote chemical transformation. Although the fundamental
      mechanism of the auto-excision from its precursor RNA has been established,
      convenient assay systems for its splicing activity are still useful for a further
      understanding of its detailed mechanism and of its application. Because some host
      RNA sequences, to which group I introns inserted form stable three-dimensional
      (3D) structures, the effects of the 3D structures of exonic elements on the
      splicing efficiency of group I introns are important but not a fully investigated
      issue. We developed an assay system for group I intron self-splicing by employing
      a fluorescent aptamer RNA (spinach RNA) as a model exonic sequence inserted by
      the Tetrahymena group I intron. We investigated self-splicing of the intron from
      spinach RNA, serving as a model exonic sequence with a 3D structure.

PMID- 27869658
TI  - Nano-Engineered Biomimetic Optical Sensors for Glucose Monitoring in Diabetes.
AB  - Diabetes is a rapidly growing disease that can be monitored at an individual
      level by controlling the blood glucose level, hence minimizing the negative
      impact of the disease. Significant research efforts have been focused on the
      design of novel and improved technologies to overcome the limitations of existing
      glucose analysis methods. In this context, nanotechnology has enabled the
      diagnosis at the single cell and molecular level with the possibility of
      incorporation in advanced molecular diagnostic biochips. Recent years have
      witnessed the exploration and synthesis of various types of nanomaterials with
      enzyme-like properties, with their subsequent integration into the design of
      biomimetic optical sensors for glucose monitoring. This review paper will provide
      insights on the type, nature and synthesis of different biomimetic nanomaterials.
      Moreover, recent developments in the integration of these nanomaterials for
      optical glucose biosensing will be highlighted, with a final discussion on the
      challenges that must be addressed for successful implementation of these nano
      devices in the clinical applications is presented.

PMID- 27869661
TI  - An Exploratory Investigation of Endotoxin Levels in Novice Long Distance
      Triathletes, and the Effects of a Multi-Strain Probiotic/Prebiotic, Antioxidant
      Intervention.
AB  - Gastrointestinal (GI) ischemia during exercise is associated with luminal
      permeability and increased systemic lipopolysaccharides (LPS). This study aimed
      to assess the impact of a multistrain pro/prebiotic/antioxidant intervention on
      endotoxin unit levels and GI permeability in recreational athletes. Thirty
      healthy participants (25 males, 5 females) were randomly assigned either a
      multistrain pro/prebiotic/antioxidant (LAB4ANTI; 30 billion CFU.day-1 containing
      10 billion CFU.day-1Lactobacillus acidophilus CUL-60 (NCIMB 30157), 10 billion
      CFU.day-1Lactobacillus acidophillus CUL-21 (NCIMB 30156), 9.5 billion CFU.day
      1Bifidobacterium bifidum CUL-20 (NCIMB 30172) and 0.5 billion CFU.day
      1Bifidobacterium animalis subspecies lactis CUL-34 (NCIMB 30153)/55.8 mg.day-1
      fructooligosaccharides/ 400 mg.day-1 alpha-lipoic acid, 600 mg.day-1N-acetyl
      carnitine); matched pro/prebiotic (LAB4) or placebo (PL) for 12 weeks preceding a
      long-distance triathlon. Plasma endotoxin units (via Limulus amebocyte lysate
      chromogenic quantification) and GI permeability (via 5 h urinary lactulose (L):
      mannitol (M) recovery) were assessed at baseline, pre-race and six days post
      race. Endotoxin unit levels were not significantly different between groups at
      baseline (LAB4ANTI: 8.20 +/- 1.60 pg.mL-1; LAB4: 8.92 +/- 1.20 pg.mL-1; PL: 9.72
      +/- 2.42 pg.mL-1). The use of a 12-week LAB4ANTI intervention significantly
      reduced endotoxin units both pre-race (4.37 +/- 0.51 pg.mL-1) and six days post
      race (5.18 +/- 0.57 pg.mL-1; p = 0.03, etap2 = 0.35), but only six days post-race
      with LAB4 (5.01 +/- 0.28 pg.mL-1; p = 0.01, etap2 = 0.43). In contrast, endotoxin
      units remained unchanged with PL. L:M significantly increased from 0.01 +/- 0.01
      at baseline to 0.06 +/- 0.01 with PL only (p = 0.004, etap2 = 0.51). Mean race
      times (h:min:s) were not statistically different between groups despite faster
      times with both pro/prebiotoic groups (LAB4ANTI: 13:17:07 +/- 0:34:48; LAB4:
      12:47:13 +/- 0:25:06; PL: 14:12:51 +/- 0:29:54; p > 0.05). Combined multistrain
      pro/prebiotic use may reduce endotoxin unit levels, with LAB4ANTI potentially
      conferring an additive effect via combined GI modulation and antioxidant
      protection.

PMID- 27869662
TI  - The Cell Killing Mechanisms of Hydroxyurea.
AB  - Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has
      a long history of scientific interest and clinical use for the treatment of
      neoplastic and non-neoplastic diseases. It is currently the staple drug for the
      management of sickle cell anemia and chronic myeloproliferative disorders. Due to
      its reversible inhibitory effect on DNA replication in various organisms,
      hydroxyurea is also commonly used in laboratories for cell cycle synchronization
      or generating replication stress. However, incubation with high concentrations or
      prolonged treatment with low doses of hydroxyurea can result in cell death and
      the DNA damage generated at arrested replication forks is generally believed to
      be the direct cause. Recent studies in multiple model organisms have shown that
      oxidative stress and several other mechanisms may contribute to the majority of
      the cytotoxic effect of hydroxyurea. This review aims to summarize the progress
      in our understanding of the cell-killing mechanisms of hydroxyurea, which may
      provide new insights towards the improvement of chemotherapies that employ this
      agent.

PMID- 27869664
TI  - Anti-Melanogenic Activity of Gagunin D, a Highly Oxygenated Diterpenoid from the
      Marine Sponge Phorbas sp., via Modulating Tyrosinase Expression and Degradation.
AB  - Tyrosinase is the rate-limiting enzyme critical for melanin synthesis and
      controls pigmentation in the skin. The inhibition of tyrosinase is currently the
      most common approach for the development of skin-whitening cosmetics. Gagunin D
      (GD), a highly oxygenated diterpenoid isolated from the marine sponge Phorbas
      sp., has exhibited cytotoxicity toward human leukemia cells. However, the effect
      of GD on normal cells and the molecular mechanisms remain to be elucidated. In
      the present study, we identified for the first time the anti-melanogenic activity
      of GD and its precise underlying mechanisms in mouse melan-a cells. GD
      significantly inhibited melanin synthesis in the melan-a cells and a
      reconstructed human skin model. Further analysis revealed that GD suppressed the
      expression of tyrosinase and increased the rate of tyrosinase degradation. GD
      also inhibited tyrosinase enzymatic activity. In addition, GD effectively
      suppressed the expression of proteins associated with melanosome transfer. These
      findings suggest that GD is a potential candidate for cosmetic formulations due
      to its multi-functional properties.

PMID- 27869663
TI  - Dietary Protein Sources and Incidence of Breast Cancer: A Dose-Response Meta
      Analysis of Prospective Studies.
AB  - Protein is important to the human body, and different sources of protein may have
      different effects on the risk of breast cancer. Thus, we conducted a meta
      analysis to investigate the association between different dietary protein sources
      and breast cancer risk. PubMed and several databases were searched until December
      2015. Relevant articles were retrieved according to specific searching criteria.
      Forty-six prospective studies were included. The summary relative risk (RR) for
      highest versus lowest intake was 1.07 (95% confidence interval (CI) 1.01-1.14, I2
      = 34.6%) for processed meat, 0.92 (95% CI 0.84-1.00, I2 = 0%) for soy food, 0.93
      (95% CI 0.85-1.00, I2 = 40.1%) for skim milk, and 0.90 (95% CI 0.82-1.00, I2 =
      0%) for yogurt. Similar conclusions were obtained in dose-response association
      for each serving increase: total red meat (RR: 1.07; 95% CI 1.01-1.14, I2 =
      7.1%), fresh red meat (RR: 1.13; 95% CI 1.01-1.26, I2 = 56.4%), processed meat
      (RR: 1.09; 95% CI 1.02-1.17, I2 = 11.8%), soy food (RR: 0.91; 95% CI 0.84-1.00,
      I2 = 0%), and skim milk (RR: 0.96; 95% CI 0.92-1.00, I2 = 11.9%). There was a
      null association between poultry, fish, egg, nuts, total milk, and whole milk
      intake and breast cancer risk. Higher total red meat, fresh red meat, and
      processed meat intake may be risk factors for breast cancer, whereas higher soy
      food and skim milk intake may reduce the risk of breast cancer.

PMID- 27869666
TI  - Gingival Crevicular Fluid as a Novel Potential Source of Biomarkers Distinguishes
      Pubertal from Post-Pubertal Subjects.
AB  - Detection of pubertal growth peak is vital in orthodontic treatment timing and
      planning. Gingival crevicular fluid (GCF) contains abundant proteins from
      different sources and has been proven to be an ideal source of biomarkers. Matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOF/MS) is an advanced technique that can detect low-molecular-weight peptides
      with high sensitivity and resolution. The aim of this research was to identify
      novel candidate biomarkers in GCF to help the diagnosis of pubertal growth peak
      by MALDI-TOF/MS. Results showed that the peak intensities of six peptides were
      significantly different between two groups: 1660.2 Da, 1783.0 Da, 2912.5 Da,
      4178.6 Da, 5064.9 Da, and 6108.9 Da and are considered to be potential candidate
      biomarkers to identify pubertal growth peak. Further studies are needed to
      identify sequence information of these candidate biomarkers.

PMID- 27869665
TI  - Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary
      Extract Polyphenols.
AB  - Cancer cells display enhanced growth rates and a resistance to apoptosis. The
      ability of cancer cells to evade homeostasis and proliferate uncontrollably while
      avoiding programmed cell death/apoptosis is acquired through mutations to key
      signaling molecules, which regulate pathways involved in cell proliferation and
      survival. Compounds of plant origin, including food components, have attracted
      scientific attention for use as agents for cancer prevention and treatment. The
      exploration into natural products offers great opportunity to evaluate new
      anticancer agents as well as understand novel and potentially relevant mechanisms
      of action. Rosemary extract has been reported to have antioxidant, anti
      inflammatory, antidiabetic and anticancer properties. Rosemary extract contains
      many polyphenols with carnosic acid and rosmarinic acid found in highest
      concentrations. The present review summarizes the existing in vitro and in vivo
      studies focusing on the anticancer effects of rosemary extract and the rosemary
      extract polyphenols carnosic acid and rosmarinic acid, and their effects on key
      signaling molecules.

PMID- 27869668
TI  - Validation of Remote Sensing Retrieval Products using Data from a Wireless Sensor
      Based Online Monitoring in Antarctica.
AB  - Of the modern technologies in polar-region monitoring, the remote sensing
      technology that can instantaneously form large-scale images has become much more
      important in helping acquire parameters such as the freezing and melting of ice
      as well as the surface temperature, which can be used in the research of global
      climate change, Antarctic ice sheet responses, and cap formation and evolution.
      However, the acquirement of those parameters is impacted remarkably by the
      climate and satellite transit time which makes it almost impossible to have
      timely and continuous observation data. In this research, a wireless sensor-based
      online monitoring platform (WSOOP) for the extreme polar environment is applied
      to obtain a long-term series of data which is site-specific and continuous in
      time. Those data are compared and validated with the data from a weather station
      at Zhongshan Station Antarctica and the result shows an obvious correlation. Then
      those data are used to validate the remote sensing products of the freezing and
      melting of ice and the surface temperature and the result also indicated a
      similar correlation. The experiment in Antarctica has proven that WSOOP is an
      effective system to validate remotely sensed data in the polar region.

PMID- 27869669
TI  - Compressed Symmetric Nested Arrays and Their Application for Direction-of-Arrival
      Estimation of Near-Field Sources.
AB  - In this paper, a new sensor array geometry, called a compressed symmetric nested
      array (CSNA), is designed to increase the degrees of freedom in the near field.
      As its name suggests, a CSNA is constructed by getting rid of some elements from
      two identical nested arrays. The closed form expressions are also presented for
      the sensor locations and the largest degrees of freedom obtainable as a function
      of the total number of sensors. Furthermore, a novel DOA estimation method is
      proposed by utilizing the CSNA in the near field. By employing this new array
      geometry, our method can identify more sources than sensors. Compared with other
      existing methods, the proposed method achieves higher resolution because of
      increased array aperture. Simulation results are demonstrated to verify the
      effectiveness of the proposed method.

PMID- 27869670
TI  - Homologous Prime-Boost Vaccination with OVA Entrapped in Self-Adjuvanting
      Archaeosomes Induces High Numbers of OVA-Specific CD8+ T Cells that Protect
      Against Subcutaneous B16-OVA Melanoma.
AB  - Homologous prime-boost vaccinations with live vectors typically fail to induce
      repeated strong CD8+ T cell responses due to the induction of anti-vector
      immunity, highlighting the need for alternative delivery vehicles. The unique
      ether lipids of archaea may be constituted into liposomes, archaeosomes, which do
      not induce anti-carrier responses, making them an ideal candidate for use in
      repeat vaccination systems. Herein, we evaluated in mice the maximum threshold of
      antigen-specific CD8+ T cell responses that may be induced by multiple homologous
      immunizations with ovalbumin (OVA) entrapped in archaeosomes derived from the
      ether glycerolipids of the archaeon Methanobrevibacter smithii (MS-OVA). Up to
      three immunizations with MS-OVA administered in optimized intervals (to allow for
      sufficient resting of the primed cells prior to boosting), induced a potent anti
      OVA CD8+ T cell response of up to 45% of all circulating CD8+ T cells. Additional
      MS-OVA injections did not add any further benefit in increasing the memory of
      CD8+ T cell frequency. In contrast, OVA expressed by Listeria monocytogenes (LM
      OVA), an intracellular bacterial vector failed to evoke a boosting effect after
      the second injection, resulting in significantly reduced antigen-specific CD8+ T
      cell frequencies. Furthermore, repeated vaccination with MS-OVA skewed the
      response increasingly towards an effector memory (CD62low) phenotype. Vaccinated
      animals were challenged with B16-OVA at late time points after vaccination (+7
      months) and were afforded protection compared to control. Therefore, archaeosomes
      constituted a robust particulate delivery system to unravel the kinetics of CD8+
      T cell response induction and memory maintenance and constitute an efficient
      vaccination regimen optimized for tumor protection.

PMID- 27869672
TI  - Analysis of Multi-Antenna GNSS Receiver Performance under Jamming Attacks.
AB  - Although antenna array-based Global Navigation Satellite System (GNSS) receivers
      can be used to mitigate both narrowband and wideband electronic interference
      sources, measurement distortions induced by array processing methods are not
      suitable for high precision applications. The measurement distortions have an
      adverse effect on the carrier phase ambiguity resolution, affecting the
      navigation solution. Depending on the array attitude information availability and
      calibration parameters, different spatial processing methods can be implemented
      although they distort carrier phase measurements in some cases. This paper
      provides a detailed investigation of the effect of different array processing
      techniques on array-based GNSS receiver measurements and navigation performance.
      The main novelty of the paper is to provide a thorough analysis of array-based
      GNSS receivers employing different beamforming techniques from tracking to
      navigation solution. Two beamforming techniques, namely Power Minimization (PM)
      and Minimum Power Distortionless Response (MPDR), are being investigated. In the
      tracking domain, the carrier Doppler, Phase Lock Indicator (PLI), and Carrier-to
      Noise Ratio (C/N0) are analyzed. Pseudorange and carrier phase measurement
      distortions and carrier phase position performance are also evaluated.
      Performance analyses results from simulated GNSS signals and field tests are
      provided.

PMID- 27869667
TI  - Metabolomics, a Powerful Tool for Agricultural Research.
AB  - Metabolomics, which is based mainly on nuclear magnetic resonance (NMR), gas
      chromatography (GC) or liquid-chromatography (LC) coupled to mass spectrometry
      (MS) analytical technologies to systematically acquire the qualitative and
      quantitative information of low-molecular-mass endogenous metabolites, provides a
      direct snapshot of the physiological condition in biological samples. As
      complements to transcriptomics and proteomics, it has played pivotal roles in
      agricultural and food science research. In this review, we discuss the capacities
      of NMR, GC/LC-MS in the acquisition of plant metabolome, and address the
      potential promise and diverse applications of metabolomics, particularly
      lipidomics, to investigate the responses of Arabidopsis thaliana, a primary plant
      model for agricultural research, to environmental stressors including heat,
      freezing, drought, and salinity.

PMID- 27869671
TI  - The Evolution of Total Phenolic Compounds and Antioxidant Activities during
      Ripening of Grapes (Vitis vinifera L., cv. Tempranillo) Grown in Semiarid Region:
      Effects of Cluster Thinning and Water Deficit.
AB  - A study was made of how water status (rainfed vs. irrigated) and crop load (no
      cluster thinning vs. cluster thinning) can together affect the grapes of Vitis
      vinifera cv. Tempranillo vines growing in a semiarid zone of Extremadura (Spain).
      The grapes were monitored at different stages of ripening, measuring the
      peroxidase (POX) and superoxide dismutase (SOD) antioxidant activities and the
      phenolic content (flavonoids and phenylpropanoids), together with other
      parameters. The irrigation regime was adjusted to provide 100% of crop
      evapotranspiration (ETc). The findings confirmed previous results that both
      thinning and water deficit advance ripening, while irrigation and high crop load
      (no thinning) lengthen the growth cycle. The SOD activity remained practically
      constant throughout ripening in the thinned treatments and was always lower than
      in the unthinned treatments, an aspect which could have been the cause of the
      observed greater level of lipid peroxidation in the water deficit, thinned
      treatment. The nonspecific peroxidase activity was very low, especially in the
      thinned treatments. The effect of thinning was enhanced when combined with water
      deficit, inducing increases in phenylpropanoids and, above all, flavonoids at the
      harvest stage of ripening, while leaving the polyphenol oxidase activity (PPO)
      unaffected.

PMID- 27869674
TI  - Transdermal Permeation and Anti-Inflammation Activities of Novel Sinomenine
      Derivatives.
AB  - Sinomenine is extracted from Sinomenii caulis (a traditional Chinese medicine),
      and it is used as the active ingredient in rheumatic arthritis treatments. It has
      been used in clinical applications for decades. However, there are some
      disadvantages, including low activity in transdermal permeation and a high dosage
      being clinically required. To overcome these defects, sinomenine was used as a
      primer, and structural modification was performed. In our study, eight new
      compounds were screened out by transdermal permeation in vitro and anti
      inflammatory response in vitro and in vivo. Compound 1a exhibited the most potent
      transdermal permeation and anti-inflammatory activity. Based on these results,
      further development of this compound may be warranted.

PMID- 27869673
TI  - 3D Visualization of Developmental Toxicity of 2,4,6-Trinitrotoluene in Zebrafish
      Embryogenesis Using Light-Sheet Microscopy.
AB  - Environmental contamination by trinitrotoluene is of global concern due to its
      widespread use in military ordnance and commercial explosives. Despite known long
      term persistence in groundwater and soil, the toxicological profile of
      trinitrotoluene and other explosive wastes have not been systematically measured
      using in vivo biological assays. Zebrafish embryos are ideal model vertebrates
      for high-throughput toxicity screening and live in vivo imaging due to their
      small size and transparency during embryogenesis. Here, we used Single Plane
      Illumination Microscopy (SPIM)/light sheet microscopy to assess the developmental
      toxicity of explosive-contaminated water in zebrafish embryos and report 2,4,6
      trinitrotoluene-associated developmental abnormalities, including defects in
      heart formation and circulation, in 3D. Levels of apoptotic cell death were
      higher in the actively developing tissues of trinitrotoluene-treated embryos than
      controls. Live 3D imaging of heart tube development at cellular resolution by
      light-sheet microscopy revealed trinitrotoluene-associated cardiac toxicity,
      including hypoplastic heart chamber formation and cardiac looping defects, while
      the real time PCR (polymerase chain reaction) quantitatively measured the
      molecular changes in the heart and blood development supporting the developmental
      defects at the molecular level. Identification of cellular toxicity in zebrafish
      using the state-of-the-art 3D imaging system could form the basis of a sensitive
      biosensor for environmental contaminants and be further valued by combining it
      with molecular analysis.

PMID- 27869675
TI  - Pterostilbene Inhibits Human Multiple Myeloma Cells via ERK1/2 and JNK Pathway In
      Vitro and In Vivo.
AB  - Multiple myeloma (MM) is the second most common malignancy in the hematologic
      system, which is characterized by accumulation of plasma cells in bone marrow.
      Pterostilbene (PTE) is a natural dimethylated analog of resveratrol, which has
      anti-oxidant, anti-inflammatory and anti-tumor properties. In the present study,
      we examined the anti-tumor effect of PTE on MM cell lines both in vitro and in
      vivo using the cell counting kit (CCK)-8, apoptosis assays, cell cycle analysis,
      reactive oxygen species (ROS) generation, JC-1 mitochondrial membrane potential
      assay, Western blotting and tumor xenograft models. The results demonstrated that
      PTE induces apoptosis in the H929 cell line and causes cell cycle arrest at G0/G1
      phase by enhancing ROS generation and reducing mitochondrial membrane potential.
      The anti-tumor effect of PTE may be caused by the activation of the extracellular
      regulated protein kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) signaling
      pathways. Additionally, mice treated with PTE by intraperitoneal injection
      demonstrated reduced tumor volume. Taken together, the results of this study
      indicate that the anti-tumor effect of PTE on MM cells may provide a new
      therapeutic option for MM patients.

PMID- 27869676
TI  - Nitrogen Removal from Landfill Leachate by Microalgae.
AB  - Landfill leachates result from the degradation of solid residues in sanitary
      landfills, thus presenting a high variability in terms of composition. Normally,
      these effluents are characterized by high ammoniacal-nitrogen (N-NH4+)
      concentrations, high chemical oxygen demands and low phosphorus concentrations.
      The development of effective treatment strategies becomes difficult, posing a
      serious problem to the environment. Phycoremediation appears to be a suitable
      alternative for the treatment of landfill leachates. In this study, the potential
      of Chlorella vulgaris for biomass production and nutrients (mainly nitrogen and
      phosphorus) removal from different compositions of a landfill leachate was
      evaluated. Since microalgae also require phosphorus for their growth, different
      loads of this nutrient were evaluated, giving the following N:P ratios: 12:1,
      23:1 and 35:1. The results have shown that C. vulgaris was able to grow in the
      different leachate compositions assessed. However, microalgal growth was higher
      in the cultures presenting the lowest N-NH4+ concentration. In terms of nutrients
      uptake, an effective removal of N-NH4+ and phosphorus was observed in all the
      experiments, especially in those supplied with phosphorus. Nevertheless, N-NO3-
      removal was considered almost negligible. These promising results constitute
      important findings in the development of a bioremediation technology for the
      treatment of landfill leachates.

PMID- 27869678
TI  - Correction: Griffith, D.M., et al. Novel Improved Synthesis of HSP70 Inhibitor,
      Pifithrin-MU. In Vitro Synergy Quantification of Pifithrin-MU Combined with Pt
      Drugs in Prostate and Colorectal Cancer Cells. Molecules 2016, 21, 949.
AB  - n/a.

PMID- 27869677
TI  - Antimicrobial Activity of Zabofloxacin against Clinically Isolated Streptococcus
      pneumoniae.
AB  - Zabofloxacin is a novel fluoroquinolone agent that has potent activity against
      gram-positive pathogens. In this study, we confirmed that zabofloxacin showed the
      most potent in vitro and in vivo activities against drug-resistant Streptococcus
      pneumoniae. Among the fluoroquinolone compounds, zabofloxacin showed the most
      potent in vitro activity against clinical isolates of penicillin-sensitive S.
      pneumoniae (minimum inhibitory concentration, MIC90: 0.03 mg/L) and penicillin
      resistant S. pneumoniae (MIC90: 0.03 mg/L). Against quinolone-resistant S.
      pneumoniae, zabofloxacin (MIC90: 1 mg/L) was more active than ciprofloxacin,
      sparfloxacin, and moxifloxacin; however, its activity was the same as that of
      gemifloxacin. The in vivo activity of zabofloxacin was most potent among the
      quinolone compounds tested against the systemic infection and respiratory tract
      infection models in mice.

PMID- 27869679
TI  - Transcriptome-Based Discovery of Fusarium graminearum Stress Responses to FgHV1
      Infection.
AB  - Fusarium graminearum hypovirus 1 (FgHV1), which is phylogenetically related to
      Cryphonectria hypovirus 1 (CHV1), is a virus in the family Hypoviridae that
      infects the plant pathogenic fungus F. graminearum. Although hypovirus FgHV1
      infection does not attenuate the virulence of the host (hypovirulence), it
      results in defects in mycelial growth and spore production. We now report that
      the vertical transmission rate of FgHV1 through asexual spores reached 100%.
      Using RNA deep sequencing, we performed genome-wide expression analysis to reveal
      phenotype-related genes with expression changes in response to FgHV1 infection. A
      total of 378 genes were differentially expressed, suggesting that hypovirus
      infection causes a significant alteration of fungal gene expression. Nearly two
      times as many genes were up-regulated as were down-regulated. A differentially
      expressed gene enrichment analysis identified a number of important pathways.
      Metabolic processes, the ubiquitination system, and especially cellular redox
      regulation were the most affected categories in F. graminearum challenged with
      FgHV1. The p20, encoded by FgHV1 could induce H2O2 accumulation and
      hypersensitive response in Nicotiana benthamiana leaves. Moreover, hypovirus
      FgHV1 may regulate transcription factors and trigger the RNA silencing pathway in
      F. graminearum.

PMID- 27869680
TI  - Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System
      Homeostasis.
AB  - Accumulating evidence suggests that gut bacteria play a role in homeostasis of
      the circulatory system in mammals. First, gut bacteria may affect the nervous
      control of the circulatory system via the sensory fibres of the enteric nervous
      system. Second, gut bacteria-derived metabolites may cross the gut-blood barrier
      and target blood vessels, the heart and other organs involved in the regulation
      of the circulatory system. A number of studies have shown that hydrogen sulfide
      (H2S) is an important biological mediator in the circulatory system. Thus far,
      research has focused on the effects of H2S enzymatically produced by
      cardiovascular tissues. However, some recent evidence indicates that H2S released
      in the colon may also contribute to the control of arterial blood pressure.
      Incidentally, sulfate-reducing bacteria are ubiquitous in mammalian colon, and
      H2S is just one among a number of molecules produced by the gut flora. Other gut
      bacteria-derived compounds that may affect the circulatory system include
      methane, nitric oxide, carbon monoxide, trimethylamine or indole. In this paper,
      we review studies that imply a role of gut microbiota and their metabolites, such
      as H2S, in circulatory system homeostasis.

PMID- 27869681
TI  - Induction of Laccase, Lignin Peroxidase and Manganese Peroxidase Activities in
      White-Rot Fungi Using Copper Complexes.
AB  - Ligninolytic enzymes, such as laccase, lignin peroxidase and manganese
      peroxidase, are biotechnologically-important enzymes. The ability of five white
      rot fungal strains Daedaleopsis confragosa, Fomes fomentarius, Trametes gibbosa,
      Trametes suaveolens and Trametes versicolor to produce these enzymes has been
      studied. Three different copper(II) complexes have been prepared
      ((Him)[Cu(im)4(H2O)2](btc).3H2O, where im = imidazole, H3btc = 1,3,5
      benzenetricarboxylic acid, [Cu3(pmdien)3(btc)](ClO4)3.6H2O) and
      [Cu3(mdpta)3(btc)](ClO4)3.4H2O, where pmdien = N,N,N',N'',N''-pentamethyl
      diethylenetriamine and mdpta = N,N-bis-(3-aminopropyl)methyl- amine), and their
      potential application for laccase and peroxidases induction have been tested. The
      enzyme-inducing activities of the complexes were compared with that of copper
      sulfate, and it has been found that all of the complexes are suitable for the
      induction of laccase and peroxidase activities in white-rot fungi; however, the
      newly-synthesized complex M1 showed the greatest potential for the induction.
      With respect to the different copper inducers, this parameter seems to be
      important for enzyme activity, which depends also on the fungal strains.

PMID- 27869682
TI  - An Indoor Monitoring System for Ambient Assisted Living Based on Internet of
      Things Architecture.
AB  - The study of systems and architectures for ambient assisted living (AAL) is
      undoubtedly a topic of great relevance given the aging of the world population.
      The AAL technologies are designed to meet the needs of the aging population in
      order to maintain their independence as long as possible. As people typically
      spend more than 90% of their time in indoor environments, indoor air quality
      (iAQ) is perceived as an imperative variable to be controlled for the
      inhabitants' wellbeing and comfort. Advances in networking, sensors, and embedded
      devices have made it possible to monitor and provide assistance to people in
      their homes. The continuous technological advancements make it possible to build
      smart objects with great capabilities for sensing and connecting several possible
      advancements in ambient assisted living systems architectures. Indoor
      environments are characterized by several pollutant sources. Most of the
      monitoring frameworks instantly accessible are exceptionally costly and only
      permit the gathering of arbitrary examples. iAQ is an indoor air quality system
      based on an Internet of Things paradigm that incorporates in its construction
      Arduino, ESP8266, and XBee technologies for processing and data transmission and
      micro sensors for data acquisition. It also allows access to data collected
      through web access and through a mobile application in real time, and this data
      can be accessed by doctors in order to support medical diagnostics. Five smaller
      scale sensors of natural parameters (air temperature, moistness, carbon monoxide,
      carbon dioxide, and glow) were utilized. Different sensors can be included to
      check for particular contamination. The results reveal that the system can give a
      viable indoor air quality appraisal in order to anticipate technical
      interventions for improving indoor air quality. Indeed indoor air quality might
      be distinctively contrasted with what is normal for a quality living environment.

PMID- 27869684
TI  - Quantitative Structure Activity Relationship of Cinnamaldehyde Compounds against
      Wood-Decaying Fungi.
AB  - Cinnamaldehyde, of the genius Cinnamomum, is a major constituent of the bark of
      the cinnamon tree and possesses broad-spectrum antimicrobial activity. In this
      study, we used best multiple linear regression (BMLR) to develop quantitative
      structure activity relationship (QSAR) models for cinnamaldehyde derivatives
      against wood-decaying fungi Trametes versicolor and Gloeophyllun trabeum. Based
      on the two optimal QSAR models, we then designed and synthesized two novel
      cinnamaldehyde compounds. The QSAR models exhibited good correlation
      coefficients: R2Tv = 0.910 for Trametes versicolor and R2Gt = 0.926 for
      Gloeophyllun trabeum. Small errors between the experimental and calculated values
      of two designed compounds indicated that these two QSAR models have strong
      predictability and stability.

PMID- 27869683
TI  - Sub-Acute Toxicity Study of Graphene Oxide in the Sprague-Dawley Rat.
AB  - Graphene oxide (GO) is an oxidized derivative of graphene used in biotechnology
      and medicine. The safety of GO is uncertain, so we evaluated its toxicity in male
      rats. Rat tail veins were injected with 2.5, 5, or 10 mg/kg GO for seven days and
      behavioral patterns, pathology, and tissue morphology were assessed. Data show
      that behaviors were not altered according to an open field test and a functional
      observational battery test, but histopathological analysis indicated that GO
      caused inflammation of the lung, liver, and spleen. GO also reduced cholesterol,
      high density lipoprotein (HDL), and low density lipoprotein (LDL). No other
      organs were modified. Thus, high concentrations of GO are toxic for the lung,
      liver, and spleen, but the mechanism by which this occurs requires more study.

PMID- 27869685
TI  - Three-Dimensional Biologically Relevant Spectrum (BRS-3D): Shape Similarity
      Profile Based on PDB Ligands as Molecular Descriptors.
AB  - The crystallized ligands in the Protein Data Bank (PDB) can be treated as the
      inverse shapes of the active sites of corresponding proteins. Therefore, the
      shape similarity between a molecule and PDB ligands indicated the possibility of
      the molecule to bind with the targets. In this paper, we proposed a shape
      similarity profile that can be used as a molecular descriptor for ligand-based
      virtual screening. First, through three-dimensional (3D) structural clustering,
      300 diverse ligands were extracted from the druggable protein-ligand database, sc
      PDB. Then, each of the molecules under scrutiny was flexibly superimposed onto
      the 300 ligands. Superimpositions were scored by shape overlap and property
      similarity, producing a 300 dimensional similarity array termed the "Three
      Dimensional Biologically Relevant Spectrum (BRS-3D)". Finally, quantitative or
      discriminant models were developed with the 300 dimensional descriptor using
      machine learning methods (support vector machine). The effectiveness of this
      approach was evaluated using 42 benchmark data sets from the G protein-coupled
      receptor (GPCR) ligand library and the GPCR decoy database (GLL/GDD). We compared
      the performance of BRS-3D with other 2D and 3D state-of-the-art molecular
      descriptors. The results showed that models built with BRS-3D performed best for
      most GLL/GDD data sets. We also applied BRS-3D in histone deacetylase 1
      inhibitors screening and GPCR subtype selectivity prediction. The advantages and
      disadvantages of this approach are discussed.

PMID- 27869686
TI  - The Association of Serum Bisphenol A with Thyroid Autoimmunity.
AB  - Introduction: Data on the association of bisphenol A (BPA) exposure and
      autoimmunity in humans is unclear. Objective: To elucidate the influence of BPA
      on thyroid autoimmunity, in the present study we assessed the association between
      serum BPA and thyroid autoantibodies. Methods: Serum samples from 2361 subjects,
      aged >=15 years, from the Thai 4th National Health Examination Survey were
      measured for BPA, antithyroglobulin (TgAb), antithyroperoxidase (TPOAb) and
      antithyrotrophin receptor (TRAb) antibodies. Results: The proportion of subjects
      positive for TgAb, TPOAb and TRAb were 11.1%, 14.9% and 1.9%, respectively. With
      regard to BPA, 51.9% had serum BPA levels exceeding the detection limit of the
      assay (0.3). There was a significant increasing trend for subjects with TgAb (p <
      0.05) and TPOAb (p < 0.001) positivity as BPA quartiles increased, particularly
      in the highest quartile. In contrast, no relationship between BPA quartiles and
      TRAb was found. Logistic regression analysis showed that age, gender and BPA
      quartiles were determinants of TPOAb or TgAb positivity, independent of BMI.
      However, only the association between BPA and TPOAb positivity was consistent in
      both men and women. Conclusions: BPA was independently associated with TPOAb
      positivity. However, its mechanism related to TPOAb positivity, subsequently
      leading to autoimmune thyroid disease, needs further investigation.

PMID- 27869687
TI  - Structure, Spatial and Temporal Distribution of the Culex pipiens Complex in
      Shanghai, China.
AB  - BACKGROUND: Culex pipiens molestus was first reported in Shanghai in 2010. The
      population structures and seasonal distributions of Culex pipiens subspecies C.
      p. molestus, Culex pipiens pallens, and Culex pipiens quinquefasciatus are not
      well known. METHODS: From late February to November 2013, we conducted daily
      field surveillance of mosquitoes at eight sites at two green lands and three
      residential areas in downtown Shanghai. Morphological comparison and DV/D ratios
      (DV/D is an indicator of mosquito taxonomy) were used to identify adult
      mosquitoes. RESULTS: The distribution curves of the Culex pipiens complex members
      indicated seasonal fluctuations. The temperature range of 20-25  degrees C was
      the most suitable for adult activity. Micro-environmental factors may
      differentiate the complex population structures. Hybridization between C. p.
      pallens and C. p. quinquefasciatus was common and neither "DV/D = 0.40" nor "DV/D
      = 0.50" can distinguish these subspecies and their hybrids. Conclusion: the
      population structure of the Culex pipiens complex is complex and characterized by
      significant hybridization. Measures other than DV/D ratios are needed for the
      discrimination of subspecies. The C. p. molestus invasion might result in the
      transmission of novel vector-borne diseases in Shanghai.

PMID- 27869688
TI  - Comparison of Secular Trends in Cervical Cancer Mortality in China and the United
      States: An Age-Period-Cohort Analysis.
AB  - Background: As one of the most common cancers in the female population, cervical
      cancer has ranked as the second most incident gynecological cancer in recent
      years, trailing only breast cancer. We aimed to assess and compare the secular
      trends in cervical cancer mortality in China and the United States and analyze
      the independent effects of chronological age, time period and birth cohort using
      age-period-cohort (APC) analysis. Methods: We performed an age-period-cohort
      analysis using the intrinsic estimator method to estimate the independent effects
      of age, time period, and birth cohort on cervical cancer mortality. We collected
      mortality data for China and the United States from the WHO Mortality Database
      and China Health Statistical Yearbook database. Results: We examined the general
      trends in cervical mortality rates in China and the United States during the
      periods 1988-2012 and 1953-2012, respectively. The age-standardized mortality
      rates (ASMRs) for cervical cancer in urban China, rural China and the U.S. showed
      a general decreasing trend during the observation period, except for urban China,
      which experienced a significant increase beginning in 2002. The mortality rates
      for cervical cancer in the three areas showed a general increasing trend with
      age, regardless of the period effect. Period effects declined steadily in both
      rural China (from 0.19 to -0.26) and the U.S. (from -0.20 to -0.43); however, a
      slight increasing trend was identified (from -0.25 to 0.33) in urban China, which
      indicated that the risk of mortality increased with time. Cohort effects peaked
      in the cohort born in 1911-1915 in both rural China and urban China, declined
      consistently in the cohort born before 1950, and then decreased again in the
      cohort born after 1976-1980. The cohort effect in the U.S. peaked in the birth
      cohort born in 1876-1880, then leveled off and slightly decreased in younger
      generations. Conclusions: Our study showed that in general, cervical cancer
      mortality rates increased with age and decreased with birth cohort in the U.S.,
      while the risk of mortality was highest in the cohort born during 1946-1975 in
      urban China. Additionally, the risk of mortality consistently increased with age
      in women younger than 64 years old in urban and rural China and began to decline
      in older groups. Although the age and cohort effects were relatively strong, the
      period effect may be the key factor affecting cervical cancer mortality trends,
      mainly reflecting the immediate effects of effective treatment and the
      implementation of screening.

PMID- 27869689
TI  - Multi-Axis Force/Torque Sensor Based on Simply-Supported Beam and
      Optoelectronics.
AB  - This paper presents a multi-axis force/torque sensor based on simply-supported
      beam and optoelectronic technology. The sensor's main advantages are: (1) Low
      power consumption; (2) low-level noise in comparison with conventional methods of
      force sensing (e.g., using strain gauges); (3) the ability to be embedded into
      different mechanical structures; (4) miniaturisation; (5) simple manufacture and
      customisation to fit a wide-range of robot systems; and (6) low-cost fabrication
      and assembly of sensor structure. For these reasons, the proposed multi-axis
      force/torque sensor can be used in a wide range of application areas including
      medical robotics, manufacturing, and areas involving human-robot interaction.
      This paper shows the application of our concept of a force/torque sensor to
      flexible continuum manipulators: A cylindrical MIS (Minimally Invasive Surgery)
      robot, and includes its design, fabrication, and evaluation tests.

PMID- 27869690
TI  - Biogenesis of Triterpene Dimers from Orthoquinones Related to Quinonemethides:
      Theoretical Study on the Reaction Mechanism.
AB  - The biogenetic origin of triterpene dimers from the Celastraceae family has been
      proposed as assisted hetero-Diels-Alder reaction (HDA). In this work,
      computational calculation of HDA between natural quinonemethides (tingenone and
      isopristimerol) and hypothetical orthoquinones has been performed at the M06-2X/6
      31G(d) level of theory. We have located all the HDA transition states supporting
      the biogenetic route via HDA cycloadditions. We found that all reactions take
      place through a concerted inverse electron demand and asynchronous mechanism. The
      enzymatic assistance for dimer formation was analyzed in terms of the calculated
      transition state energy barrier.

PMID- 27869693
TI  - Putting the Barker Theory into the Future: Time to Act on Preventing Pediatric
      Obesity.
AB  - Growth and development are key characteristics of childhood and sensitive markers
      of health and adequate nutrition. The first 1000 days of life-conception through
      24 months of age-represent a fundamental period for development and thus the
      prevention of childhood obesity and its adverse consequences is mandatory. There
      are many growth drivers during this complex phase of life, such as nutrition,
      genetic and epigenetic factors, and hormonal regulation. The challenge thus
      involves maximizing the potential for normal growth without increasing the risk
      of associated disorders. The Mediterranean Nutrition Group (MeNu Group), a group
      of researchers of the Mediterranean Region, in this Special Issue titled "Prevent
      Obesity in the First 1000 Days", presented results that advanced the science of
      obesity risk factors in early life, coming both from animal model studies and
      studies in humans. In the future, early-life intervention designs for the
      prevention of pediatric obesity will need to look at different strategies, and
      the MeNu Group is available for guidance regarding an appropriate conceptual
      framework to accomplish either prevention or treatment strategies to tackle
      pediatric obesity.

PMID- 27869692
TI  - A Stereocontrolled Protocol to Highly Functionalized Fluorinated Scaffolds
      through a Fluoride Opening of Oxiranes.
AB  - A novel selective and substrate-dependent synthetic protocol has been developed
      towards the synthesis of various fluorine-containing, highly functionalized
      cycloalkane derivatives. The method involves the stereoselective epoxidation of
      some unsaturated cyclic beta-amino acid derivatives as model compounds, followed
      by a regioselective fluoride opening of oxiranes under various conditions with
      Deoxofluor and XtalFluor-E reagents, thereby offering an insight into this new
      epoxide opening methodology with fluoride.

PMID- 27869691
TI  - Bacterial Biotransformation of Pentachlorophenol and Micropollutants Formed
      during Its Production Process.
AB  - Pentachlorophenol (PCP) is a toxic and persistent wood and cellulose preservative
      extensively used in the past decades. The production process of PCP generates
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) as
      micropollutants. PCDD/Fs are also known to be very persistent and dangerous for
      human health and ecosystem functioning. Several physico-chemical and biological
      technologies have been used to remove PCP and PCDD/Fs from the environment.
      Bacterial degradation appears to be a cost-effective way of removing these
      contaminants from soil while causing little impact on the environment. Several
      bacteria that cometabolize or use these pollutants as their sole source of carbon
      have been isolated and characterized. This review summarizes current knowledge on
      the metabolic pathways of bacterial degradation of PCP and PCDD/Fs. PCP can be
      successfully degraded aerobically or anaerobically by bacteria. Highly
      chlorinated PCDD/Fs are more likely to be reductively dechlorinated, while less
      chlorinated PCDD/Fs are more prone to aerobic degradation. The biochemical and
      genetic basis of these pollutants' degradation is also described. There are
      several documented studies of effective applications of bioremediation techniques
      for the removal of PCP and PCDD/Fs from soil and sediments. These findings
      suggest that biodegradation can occur and be applied to treat these contaminants.

PMID- 27869694
TI  - The C-Terminal O-S Acyl Shift Pathway under Acidic Condition to Propose Peptide
      Thioesters.
AB  - Peptide-thioester is a pivotal intermediate for peptide ligation and N-, C
      terminal cyclization. In this study, desired pathway and the side products of two
      C-terminal handles, hydroxyethylthiol (HET) and hydroxypropylthiol (HPT) are
      described in different conditions as well as kinetic studies. In addition, a new
      mechanism of C-terminal residue racemization is proposed on the basis of
      differentiation of products derived from the two C-terminal handles in preparing
      peptide thioesters through an acid-catalyzed tandem thiol switch, first by an
      intramolecular O-S acyl shift, and then by an intermolecular S-S exchange.

PMID- 27869695
TI  - Studies in a Murine Model Confirm the Safety of Griffithsin and Advocate Its
      Further Development as a Microbicide Targeting HIV-1 and Other Enveloped Viruses.
AB  - Griffithsin (GRFT), a lectin from Griffithsia species, inhibits human
      immunodeficiency virus-1 (HIV-1) replication at sub-nanomolar concentrations,
      with limited cellular toxicity. However, in vivo safety of GRFT is not fully
      understood, especially following parenteral administration. We first assessed
      GRFT's effects in vitro, on mouse peripheral blood mononuclear cell (mPBMC)
      viability, mitogenicity, and activation using flow-cytometry, as well as cytokine
      secretion through enzyme-linked immunosorbent assay (ELISA). Toxicological
      properties of GRFT were determined after a single subcutaneous administration of
      50 mg/kg or 14 daily doses of 10 mg/kg in BALB/c mice. In the context of
      microbicide development, toxicity of GRFT at 2 mg/kg was determined after
      subcutaneous, intravaginal, and intraperitoneal administrations, respectively.
      Interestingly, GRFT caused no significant cell death, mitogenicity, activation,
      or cytokine release in mPBMCs, validating the usefulness of a mouse model. An
      excellent safety profile for GRFT was obtained in vivo: no overt changes were
      observed in animal fitness, blood chemistry or CBC parameters. Following GRFT
      treatment, reversible splenomegaly was observed with activation of certain spleen
      B and T cells. However, spleen tissues were not pathologically altered by GRFT
      (either with a single high dose or chronic doses). Finally, no detectable
      toxicity was found after mucosal or systemic treatment with 2 mg/kg GRFT, which
      should be further developed as a microbicide for HIV prevention.

PMID- 27869697
TI  - Characteristics of the Protoporphyrin IX Binding Sites on Human Serum Albumin
      Using Molecular Docking.
AB  - Human serum albumin (HSA) is the main plasma protein responsible for a
      distribution of drugs in the human circulatory system. The binding to HSA is one
      of the factors that determines both the pharmacological actions and the side
      effects of drugs. The derivative of heme, protoporphyrin IX (PpIX), is a
      hydrophobic photosensitizer widely used in photodynamic diagnosis and therapy of
      various malignant disorders. Using absorption and fluorescence spectroscopy, it
      has been demonstrated that PpIX forms complexes with HSA. Its binding sites in
      the tertiary structure of HSA were found in the subdomains IB and IIA. PpIX binds
      to HSA in one class of binding sites with the association constant of 1.68 * 105
      M-1 and 2.30 * 105 M-1 for an excitation at wavelength lambdaex = 280 nm and 295
      nm, respectively. The binding interactions between HSA and PpIX have been studied
      by means of molecular docking simulation using the CLC Drug Discovery Workbench
      (CLC DDWB) computer program. PpIX creates a strong 'sandwich-type' complex
      between its highly conjugated porphine system and aromatic side chains of
      tryptophan and tyrosine. In summary, fluorescent studies on binding interactions
      between HSA and PpIX have been confirmed by the results of computer simulation.

PMID- 27869698
TI  - Podophyllotoxin-Loaded Nanostructured Lipid Carriers for Skin Targeting: In Vitro
      and In Vivo Studies.
AB  - Nanostructured lipid carriers (NLC) exhibit high skin targeting efficiency and
      good safety. They are promising vehicles for topical drug delivery. This study
      aims to increase the skin distribution of podophyllotoxin (POD) by incorporating
      it into NLCs. Two kinds of POD-loaded NLCs (POD-NLCs)-POD-NLCformulation 1 and
      POD-NLCformulation 2-were prepared and characterized. Their skin targeting
      efficiencies were compared by conducting in vitro and in vivo experiments.
      Obviously smaller mean particle size was observed for POD-NLCformulation 1 (106
      nm) than POD-NLCformulation 2 (219 nm), whereas relatively low POD loadings (less
      than 0.5%) were observed for both POD-NLCformulation 1 (0.33%) and POD
      NLCformulation 2 (0.49%). Significantly higher in vitro and in vivo rat skin
      deposit amounts of POD (p ? 0.01) were detected after the topical application of
      POD-NLCformulation 1 compared to POD-NLCformulation 2. To visualize the skin
      distribution behavior of hydrophobic active pharmaceutical ingredients (APIs)
      when NLCs were used as carriers, POD was replaced with Nile red (NR-a hydrophobic
      fluorescent probe), and the distribution behavior of NR-NLCformulation 1 and NR
      NLCformulation 2 in rat skin in vivo was observed using confocal laser scanning
      microscopy (CLSM). Higher fluorescent intensity was observed in rat skin after
      the topical application of NR-NLCformulation 1 than NR-NLCformulation 2,
      suggesting that higher skin targeting efficiency might be obtained when NLCs with
      smaller mean particle size were used as carriers for hydrophobic APIs. This
      result was in accordance with those of skin distribution evaluation experiments
      of POD-NLCs. Skin irritation property of POD-NLCformulation 1 was investigated
      and no irritation was observed in intact or damaged rabbit skin, suggesting it is
      safe for topical use. Our results validated the safety of NLCs when applied
      topically. More importantly, mean particle size might be an important parameter
      for formulation optimization when NLCs are used as carriers for hydrophobic APIs
      for topical application, considering that their loading is relatively low.

PMID- 27869696
TI  - Pilot-Scale Production and Thermostability Improvement of the M23 Protease
      Pseudoalterin from the Deep Sea Bacterium Pseudoalteromonas sp. CF6-2.
AB  - Pseudoalterin is the most abundant protease secreted by the marine sedimental
      bacterium Pseudoalteromonas sp. CF6-2 and is a novel cold-adapted metalloprotease
      of the M23 family. Proteases of the M23 family have high activity towards
      peptidoglycan and elastin, suggesting their promising biomedical and
      biotechnological potentials. To lower the fermentive cost and improve the
      pseudoalterin production of CF6-2, we optimized the fermentation medium by using
      single factor experiments, added 0.5% sucrose as a carbon source, and lowered the
      usage of artery powder from 1.2% to 0.6%. In the optimized medium, pseudoalterin
      production reached 161.15 +/- 3.08 U/mL, 61% greater than that before
      optimization. We further conducted a small-scale fermentation experiment in a 5-L
      fermenter and a pilot-scale fermentation experiment in a 50-L fermenter.
      Pseudoalterin production during pilot-scale fermentation reached 103.48 +/- 8.64
      U/mL, 77% greater than that before the medium was optimized. In addition, through
      single factor experiments and orthogonal tests, we developed a compound
      stabilizer for pseudoalterin, using medically safe sugars and polyols. This
      stabilizer showed a significant protective effect for pseudoalterin against
      enzymatic thermal denaturation. These results lay a solid foundation for the
      industrial production of pseudoalterin and the development of its biomedical and
      biotechnological potentials.

PMID- 27869699
TI  - Palladium(ii)-Acetylacetonato Complexes with Mesoionic Carbenes: Synthesis,
      Structures and Their Application in the Suzuki-Miyaura Cross Coupling Reaction.
AB  - A series of novel palladium(ii) acetylacetonato complexes bearing mesoionic
      carbenes (MICs) have been synthesized and characterized. The synthesis of the
      complexes of type (MIC)Pd(acac)I (MIC = 1-mesityl-3-methyl-4-phenyl-1,2,3-triazol
      5-ylidene (1), 1,4-(2,4,6-methyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (2),
      1,4-(2,6-diisopropyl)-phenyl-3-methyl-1,2,3-triazol-5-ylidene (3); acac =
      acetylacetonato) via direct metalation starting from the corresponding triazolium
      iodides and palladium(ii) acetylacetonate is described herein. All complexes were
      characterized by 1H- and 13C-NMR spectroscopy and high resolution mass
      spectrometry. Additionally, two of the complexes were characterized by single
      crystal X-ray crystallography confirming a square-planar coordination geometry of
      the palladium(ii) center. A delocalized bonding situation was observed within the
      triazolylidene rings as well as for the acac ligand respectively. Complex 2 was
      found to be an efficient pre-catalyst for the Suzuki-Miyaura cross coupling
      reaction between aryl-bromides or -chlorides with phenylboronic acid.

PMID- 27869700
TI  - Preclinical and Clinical Studies on Antioxidative, Antihypertensive and
      Cardioprotective Effect of Marine Proteins and Peptides-A Review.
AB  - High seafood consumption has traditionally been linked to a reduced risk of
      cardiovascular diseases, mainly due to the lipid lowering effects of the long
      chained omega 3 fatty acids. However, fish and seafood are also excellent sources
      of good quality proteins and emerging documentation show that, upon digestion,
      these proteins are sources for bioactive peptides with documented favorable
      physiological effects such as antioxidative, antihypertensive and other
      cardioprotective effects. This documentation is mainly from in vitro studies, but
      also animal studies are arising. Evidence from human studies evaluating the
      positive health effects of marine proteins and peptides are scarce. In one study,
      a reduction in oxidative stress after intake of cod has been documented and a few
      human clinical trials have been performed evaluating the effect on blood
      pressure. The results are, however, inconclusive. The majority of the human
      clinical trials performed to investigate positive health effects of marine
      protein and lean fish intake, has focused on blood lipids. While some studies
      have documented a reduction in triglycerides after intake of lean fish, others
      have documented no effects.

PMID- 27869701
TI  - The Role of Individual Disulfide Bonds of MU-Conotoxin GIIIA in the Inhibition of
      NaV1.4.
AB  - MU-Conotoxin GIIIA, a peptide toxin isolated from Conus geographus,
      preferentially blocks the skeletal muscle sodium channel NaV1.4. GIIIA folds
      compactly to a pyramidal structure stabilized by three disulfide bonds. To assess
      the contributions of individual disulfide bonds of GIIIA to the blockade of
      NaV1.4, seven disulfide-deficient analogues were prepared and characterized, each
      with one, two, or three pairs of disulfide-bonded Cys residues replaced with Ala.
      The inhibitory potency of the analogues against NaV1.4 was assayed by whole cell
      patch-clamp on rNaV1.4, heterologously expressed in HEK293 cells. The
      corresponding IC50 values were 0.069 +/- 0.005 MUM for GIIIA, 2.1 +/- 0.3 MUM for
      GIIIA-1, 3.3 +/- 0.2 MUM for GIIIA-2, and 15.8 +/- 0.8 MUM for GIIIA-3 (-1, -2
      and -3 represent the removal of disulfide bridges Cys3-Cys15, Cys4-Cys20 and
      Cys10-Cys21, respectively). Other analogues were not active enough for IC50
      measurement. Our results indicate that all three disulfide bonds of GIIIA are
      required to produce effective inhibition of NaV1.4, and the removal of any one
      significantly lowers its sodium channel binding affinity. Cys10-Cys21 is the most
      important for the NaV1.4 potency.

PMID- 27869702
TI  - EPS-Then and Now.
AB  - "Slime" played a brief and spectacular role in the 19th century founded by the
      theory of primordial slime by Ernst Haeckel. However, that substance was never
      found and eventually abandoned. Further scientific attention slowly began in the
      1930s referring to slime as a microbial product and then was inspired by "How
      bacteria stick" by Costerton et al. in 1978, and the matrix material was
      considered to be polysaccharides. Later, it turned out that proteins, nucleic
      acids and lipids were major other constituents of the extracellular polymeric
      substances (EPS), an acronym which was highly discussed. The role of the EPS
      matrix turns out to be fundamental for biofilms, in terms of keeping cells in
      proximity and allowing for extended interaction, resource capture, mechanical
      strength and other properties, which emerge from the life of biofilm organisms,
      including enhanced tolerance to antimicrobials and other stress. The EPS
      components are extremely complex and dynamic and fulfil many functional roles,
      turning biofilms into the most ubiquitous and successful form of life on Earth.

PMID- 27869704
TI  - A Node Localization Algorithm Based on Multi-Granularity Regional Division and
      the Lagrange Multiplier Method in Wireless Sensor Networks.
AB  - With the integrated development of the Internet, wireless sensor technology,
      cloud computing, and mobile Internet, there has been a lot of attention given to
      research about and applications of the Internet of Things. A Wireless Sensor
      Network (WSN) is one of the important information technologies in the Internet of
      Things; it integrates multi-technology to detect and gather information in a
      network environment by mutual cooperation, using a variety of methods to process
      and analyze data, implement awareness, and perform tests. This paper mainly
      researches the localization algorithm of sensor nodes in a wireless sensor
      network. Firstly, a multi-granularity region partition is proposed to divide the
      location region. In the range-based method, the RSSI (Received Signal Strength
      indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed
      by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized
      by the use of dividing region. Rach anchor node is regarded as the center of each
      region; the whole position region is divided into several regions and the sub
      region of neighboring nodes is combined into triangles while the unknown node is
      locked in the ultimate area. Secondly, the multi-granularity regional division
      and Lagrange multiplier method are used to calculate the final coordinates.
      Because nodes are influenced by many factors in the practical application, two
      kinds of positioning methods are designed. When the unknown node is inside
      positioning unit, we use the method of vector similarity. Moreover, we use the
      centroid algorithm to calculate the ultimate coordinates of unknown node. When
      the unknown node is outside positioning unit, we establish a Lagrange equation
      containing the constraint condition to calculate the first coordinates.
      Furthermore, we use the Taylor expansion formula to correct the coordinates of
      the unknown node. In addition, this localization method has been validated by
      establishing the real environment.

PMID- 27869703
TI  - Occurrence of Fusarium Mycotoxins in Cereal Crops and Processed Products (Ogi)
      from Nigeria.
AB  - In Nigeria, maize, sorghum, and millet are very important cash crops. They are
      consumed on a daily basis in different processed forms in diverse cultural
      backgrounds. These crops are prone to fungi infestation, and subsequently may be
      contaminated with mycotoxins. A total of 363 samples comprising of maize (136),
      sorghum (110), millet (87), and ogi (30) were collected from randomly selected
      markets in four agro-ecological zones in Nigeria. Samples were assessed for
      Fusarium mycotoxins contamination using a multi-mycotoxin liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method. Subsequently, some selected samples
      were analysed for the occurrence of hidden fumonisins. Overall, 64% of the
      samples were contaminated with at least one toxin, at the rate of 77%, 44%, 59%,
      and 97% for maize, sorghum, millet, and ogi, respectively. Fumonisins were the
      most dominant, especially in maize and ogi, occurring at the rate of 65% and 93%
      with mean values of 935 and 1128 MUg/kg, respectively. The prevalence of
      diacetoxyscirpenol was observed in maize (13%), sorghum (18%), and millet (29%),
      irrespective of the agro-ecological zone. Other mycotoxins detected were
      deoxynivalenol, zearalenone, and their metabolites, nivalenol, fusarenon-X, HT-2
      toxin, and hidden fumonisins. About 43% of the samples were contaminated with
      more than one toxin. This study suggests that consumption of cereals and cereal
      based products, ogi particularly by infants may be a source of exposure to
      Fusarium mycotoxins.

PMID- 27869706
TI  - Mycotoxin Contamination in Sugarcane Grass and Juice: First Report on Detection
      of Multiple Mycotoxins and Exposure Assessment for Aflatoxins B1 and G1 in
      Humans.
AB  - This study was conducted to investigate the natural co-occurrence of multiple
      toxic fungal and bacterial metabolites in sugarcane grass and juice intended for
      human consumption in Upper Egypt. Quantification of the target analytes has been
      done using the "dilute and shoot" approach followed by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). A total number of 29 and 33 different
      metabolites were detected in 21 sugarcane grass and 40 juice samples,
      respectively, with a trend of concentrations being higher in grass than in juice.
      Among the regulated mycotoxins, only aflatoxin B1 (AFB1) and aflatoxin G1 (AFG1)
      were detected. The prevalence of AFB1 was in 48% of grass samples and in 58% of
      juice with a maximum concentration of 30.6 MUg/kg and 2.10 MUg/kg, respectively.
      AFG1 was detected in 10% of grass samples (7.76 MUg/kg) and 18% of juice samples
      (34 MUg/kg). Dietary exposure was assessed using a juice frequency questionnaire
      of adult inhabitants in Assiut City. The assessment revealed different levels of
      exposure to AFB1 between males and females in winter and summer seasons. The
      estimated seasonal exposure ranged from 0.20 to 0.40 ng/kg b.w./day in winter and
      from 0.38 to 0.90 ng/kg b.w./day in summer.

PMID- 27869708
TI  - The Development of a Gas-Liquid Two-Phase Flow Sensor Applicable to CBM Wellbore
      Annulus.
AB  - The measurement of wellbore annulus gas-liquid two-phase flow in CBM (coalbed
      methane) wells is of great significance for reasonably developing gas drainage
      and extraction processes, estimating CBM output, judging the operating conditions
      of CBM wells and analyzing stratum conditions. Hence, a specially designed sensor
      is urgently needed for real-time measurement of gas-liquid two-phase flow in CBM
      wellbore annulus. Existing flow sensors fail to meet the requirements of the
      operating conditions of CBM wellbore annulus due to such factors as an
      inapplicable measurement principle, larger size, poor sealability, high
      installation accuracy, and higher requirements for fluid media. Therefore, based
      on the principle of a target flowmeter, this paper designs a new two-phase flow
      sensor that can identify and automatically calibrate different flow patterns of
      two-phase flows. Upon the successful development of the new flow sensor, lab and
      field tests were carried out, and the results show that the newly designed
      sensor, with a measurement accuracy of +/-2.5%, can adapt to the operating
      conditions of CBM wells and is reliable for long-term work.

PMID- 27869705
TI  - The Combined Application of the Caco-2 Cell Bioassay Coupled with In Vivo (Gallus
      gallus) Feeding Trial Represents an Effective Approach to Predicting Fe
      Bioavailability in Humans.
AB  - Research methods that predict Fe bioavailability for humans can be extremely
      useful in evaluating food fortification strategies, developing Fe-biofortified
      enhanced staple food crops and assessing the Fe bioavailability of meal plans
      that include such crops. In this review, research from four recent poultry
      (Gallus gallus) feeding trials coupled with in vitro analyses of Fe-biofortified
      crops will be compared to the parallel human efficacy studies which used the same
      varieties and harvests of the Fe-biofortified crops. Similar to the human
      studies, these trials were aimed to assess the potential effects of regular
      consumption of these enhanced staple crops on maintenance or improvement of iron
      status. The results demonstrate a strong agreement between the in vitro/in vivo
      screening approach and the parallel human studies. These observations therefore
      indicate that the in vitro/Caco-2 cell and Gallus gallus models can be integral
      tools to develop varieties of staple food crops and predict their effect on iron
      status in humans. The cost-effectiveness of this approach also means that it can
      be used to monitor the nutritional stability of the Fe-biofortified crop once a
      variety has released and integrated into the food system. These screening tools
      therefore represent a significant advancement to the field for crop development
      and can be applied to ensure the sustainability of the biofortification approach.

PMID- 27869707
TI  - Ex-Vivo Characterization of Bioimpedance Spectroscopy of Normal, Ischemic and
      Hemorrhagic Rabbit Brain Tissue at Frequencies from 10 Hz to 1 MHz.
AB  - Stroke is a severe cerebrovascular disease and is the second greatest cause of
      death worldwide. Because diagnostic tools (CT and MRI) to detect acute stroke
      cannot be used until the patient reaches the hospital setting, a portable
      diagnostic tool is urgently needed. Because biological tissues have different
      impedance spectra under normal physiological conditions and different
      pathological states, multi-frequency electrical impedance tomography (MFEIT) can
      potentially detect stroke. Accurate impedance spectra of normal brain tissue
      (gray and white matter) and stroke lesions (ischemic and hemorrhagic tissue) are
      important elements when studying stroke detection with MFEIT. To our knowledge,
      no study has comprehensively measured the impedance spectra of normal brain
      tissue and stroke lesions for the whole frequency range of 1 MHz within as short
      as possible an ex vivo time and using the same animal model. In this study, we
      established intracerebral hemorrhage and ischemic models in rabbits, then
      measured and analyzed the impedance spectra of normal brain tissue and stroke
      lesions ex vivo within 15 min after animal death at 10 Hz to 1 MHz. The results
      showed that the impedance spectra of stroke lesions significantly differed from
      those of normal brain tissue; the ratio of change in impedance of ischemic and
      hemorrhagic tissue with regard to frequency was distinct; and tissue type could
      be discriminated according to its impedance spectra. These findings further
      confirm the feasibility of detecting stroke with MFEIT and provide data
      supporting further study of MFEIT to detect stroke.

PMID- 27869710
TI  - Simulation of Attacks for Security in Wireless Sensor Network.
AB  - The increasing complexity and low-power constraints of current Wireless Sensor
      Networks (WSN) require efficient methodologies for network simulation and
      embedded software performance analysis of nodes. In addition, security is also a
      very important feature that has to be addressed in most WSNs, since they may work
      with sensitive data and operate in hostile unattended environments. In this
      paper, a methodology for security analysis of Wireless Sensor Networks is
      presented. The methodology allows designing attack-aware embedded
      software/firmware or attack countermeasures to provide security in WSNs. The
      proposed methodology includes attacker modeling and attack simulation with
      performance analysis (node's software execution time and power consumption
      estimation). After an analysis of different WSN attack types, an attacker model
      is proposed. This model defines three different types of attackers that can
      emulate most WSN attacks. In addition, this paper presents a virtual platform
      that is able to model the node hardware, embedded software and basic wireless
      channel features. This virtual simulation analyzes the embedded software behavior
      and node power consumption while it takes into account the network deployment and
      topology. Additionally, this simulator integrates the previously mentioned
      attacker model. Thus, the impact of attacks on power consumption and software
      behavior/execution-time can be analyzed. This provides developers with essential
      information about the effects that one or multiple attacks could have on the
      network, helping them to develop more secure WSN systems. This WSN attack
      simulator is an essential element of the attack-aware embedded software
      development methodology that is also introduced in this work.

PMID- 27869709
TI  - Cerebral Microvascular and Systemic Effects Following Intravenous Administration
      of the Perfluorocarbon Emulsion Perftoran.
AB  - Oxygen-carrying perfluorocarbon (PFC) fluids have the potential to increase
      tissue oxygenation during hypoxic states and to reduce ischemic cell death.
      Regulatory approval of oxygen therapeutics was halted due to concerns over
      vasoconstrictive side effects. The goal of this study was to assess the potential
      vasoactive properties of Perftoran by measuring brain pial arteriolar diameters
      in a healthy rat model. Perftoran, crystalloid (saline) or colloid (Hextend)
      solutions were administered as four sequential 30 min intravenous (IV) infusions,
      thus allowing an evaluation of cumulative dose-dependent effects. There were no
      overall changes in diameters of small-sized (<50 MUm) pial arterioles within the
      Perftoran group, while both saline and Hextend groups exhibited vasoconstriction.
      Medium-sized arterioles (50-100 MUm) showed minor (~8-9%) vasoconstriction within
      saline and Hextend groups and only ~5% vasoconstriction within the Perftoran
      group. For small- and medium-sized pial arterioles, the mean percent change in
      vessel diameters was not different among the groups. Although there was a
      tendency for arterial blood pressures to increase with Perftoran, pressures were
      not different from the other two groups. These data show that Perftoran, when
      administered to healthy anesthetized rats, does not cause additional
      vasoconstriction in cerebral pial arterioles or increase systemic blood pressure
      compared with saline or Hextend.

PMID- 27869711
TI  - Preparation and Characterization of Hydrophilically Modified PVDF Membranes by a
      Novel Nonsolvent Thermally Induced Phase Separation Method.
AB  - In this study, a nonsolvent thermally-induced phase separation (NTIPS) method was
      first proposed to fabricate hydrophilically-modified poly(vinylidene fluoride)
      (PVDF) membranes to overcome the drawbacks of conventional thermally-induced
      phase separation (TIPS) and nonsolvent-induced phase separation (NIPS) methods.
      Hydrophilically-modified PVDF membranes were successfully prepared by blending in
      hydrophilic polymer polyvinyl alcohol (PVA) at 140  degrees C. A series of
      PVDF/PVA blend membranes was prepared at different total polymer concentrations
      and blend ratios. The morphological analysis via SEM indicated that the formation
      mechanism of these hydrophilically-modified membranes was a combined NIPS and
      TIPS process. As the total polymer concentration increased, the tensile strength
      of the membranes increased; meanwhile, the membrane pore size, porosity and water
      flux decreased. With the PVDF/PVA blend ratio increased from 10:0 to 8:2, the
      membrane pore size and water flux increased. The dynamic water contact angle of
      these membranes showed that the hydrophilic properties of PVDF/PVA blend
      membranes were prominently improved. The higher hydrophilicity of the membranes
      resulted in reduced membrane resistance and, hence, higher permeability. The
      total resistance Rt of the modified PVDF membranes decreased significantly as the
      hydrophilicity increased. The irreversible fouling related to pore blocking and
      adsorption fouling onto the membrane surface was minimal, indicating good
      antifouling properties.

PMID- 27869714
TI  - Beverage Consumption Habits around the World: The Burden of Disease Attributable
      to Hydration.
AB  - Dehydration occurs when the body loses more water than is taken in.[...].

PMID- 27869712
TI  - Beneficial Effects of Pterocarpan-High Soybean Leaf Extract on Metabolic Syndrome
      in Overweight and Obese Korean Subjects: Randomized Controlled Trial.
AB  - Pterocarpans are known to have antifungal and anti-inflammatory properties.
      However, little is known about the changes in transcriptional profiles in
      response to a pterocarpan-high soybean leaf extract (PT). Therefore, this study
      investigated the effects of PT on blood glucose and lipid levels, as well as on
      the inflammation-related gene expression based on a peripheral blood mononuclear
      cells (PBMCs) mRNA sequencing analysis in Korean overweight and obese subjects
      with mild metabolic syndrome. The participants were randomly assigned to two
      groups and were administered either placebo (starch, 3 g/day) or PT (2 g/day) for
      12 weeks. The PT intervention did not change body weight, body fat percentage and
      body mass index (BMI). However, PT significantly decreased the glycosylated
      hemoglobin (HbA1c), plasma glucose, free fatty acid, total cholesterol, and non
      HDL cholesterol levels after 12 weeks. Furthermore, PT supplementation
      significantly lowered the homeostatic index of insulin resistance, as well as the
      plasma levels of inflammatory markers. Finally, the mRNA sequencing analysis
      revealed that PT downregulated genes related to immune responses. PT
      supplementation is beneficial for the improvement of metabolic syndrome by
      altering the fasting blood and plasma glucose, HbA1c, plasma lipid levels and
      inflammation-related gene expression in PBMCs.

PMID- 27869713
TI  - Role of Pea Enation Mosaic Virus Coat Protein in the Host Plant and Aphid Vector.
AB  - Understanding the molecular mechanisms involved in plant virus-vector
      interactions is essential for the development of effective control measures for
      aphid-vectored epidemic plant diseases. The coat proteins (CP) are the main
      component of the viral capsids, and they are implicated in practically every
      stage of the viral infection cycle. Pea enation mosaic virus 1 (PEMV1,
      Enamovirus, Luteoviridae) and Pea enation mosaic virus 2 (PEMV2, Umbravirus,
      Tombusviridae) are two RNA viruses in an obligate symbiosis causing the pea
      enation mosaic disease. Sixteen mutant viruses were generated with mutations in
      different domains of the CP to evaluate the role of specific amino acids in viral
      replication, virion assembly, long-distance movement in Pisum sativum, and aphid
      transmission. Twelve mutant viruses were unable to assemble but were able to
      replicate in inoculated leaves, move long-distance, and express the CP in newly
      infected leaves. Four mutant viruses produced virions, but three were not
      transmissible by the pea aphid, Acyrthosiphon pisum. Three-dimensional modeling
      of the PEMV CP, combined with biological assays for virion assembly and aphid
      transmission, allowed for a model of the assembly of PEMV coat protein subunits.

PMID- 27869715
TI  - Randomized Prospective Double-Blind Studies to Evaluate the Cognitive Effects of
      Inositol-Stabilized Arginine Silicate in Healthy Physically Active Adults.
AB  - Inositol-stabilized arginine silicate (ASI; Nitrosigine(r)) has been validated to
      increase levels of arginine, silicon and nitric oxide production. To evaluate
      potential enhancement of mental focus and clarity, ASI (1500 mg/day) was tested
      in two double-blind placebo-controlled crossover (DBPC-X) studies using the Trail
      Making Test (TMT, Parts A and B). In the two studies, healthy males took ASI for
      14 and 3 days, respectively. In the first study, after 14 days of dosing, TMT B
      time decreased significantly from baseline (28% improvement, p = 0.045). In the
      second study evaluating shorter-term effects, TMT B time decreased significantly
      compared to placebo (33% improvement, p = 0.024) in a 10-min period. After 3 days
      of dosing, TMT B time significantly decreased from baseline scores (35%
      improvement, p < 0.001). These findings show that ASI significantly improved the
      ability to perform complex cognitive tests requiring mental flexibility,
      processing speed and executive functioning.

PMID- 27869716
TI  - A Genome-Wide Identification and Analysis of the Basic Helix-Loop-Helix
      Transcription Factors in Brown Planthopper, Nilaparvata lugens.
AB  - The basic helix-loop-helix (bHLH) transcription factors in insects play essential
      roles in multiple developmental processes including neurogenesis, sterol
      metabolism, circadian rhythms, organogenesis and formation of olfactory sensory
      neurons. The identification and function analysis of bHLH family members of the
      most destructive insect pest of rice, Nilaparvata lugens, may provide novel tools
      for pest management. Here, a genome-wide survey for bHLH sequences identified 60
      bHLH sequences (NlbHLHs) encoded in the draft genome of N. lugens. Phylogenetic
      analysis of the bHLH domains successfully classified these genes into 40 bHLH
      families in group A (25), B (14), C (10), D (1), E (8) and F (2). The number of
      NlbHLHs with introns is higher than many other insect species, and the average
      intron length is shorter than those of Acyrthosiphon pisum. High number of
      ortholog families of NlbHLHs was found suggesting functional conversation for
      these proteins. Compared to other insect species studied, N. lugens has the
      highest number of bHLH members. Furthermore, gene duplication events of SREBP,
      Kn(col), Tap, Delilah, Sim, Ato and Crp were found in N. lugens. In addition, a
      putative full set of NlbHLH genes is defined and compared with another insect
      species. Thus, our classification of these NlbHLH members provides a platform for
      further investigations of bHLH protein functions in the regulation of N. lugens,
      and of insects in general.

PMID- 27869717
TI  - Inflammatory Properties of Diet and Glucose-Insulin Homeostasis in a Cohort of
      Iranian Adults.
AB  - We aimed to investigate associations of the dietary inflammatory index (DII) with
      glucose-insulin homeostasis markers, and the risk of glucose intolerance. This
      cross-sectional study included 2975 adults from the Tehran Lipid and Glucose
      Study. Fasting plasma glucose (FPG), 2-h post-load glucose (2h-PG), and fasting
      serum insulin were measured. Homeostatic model assessment of insulin resistance
      index (HOMA-IR) and beta-cell function (HOMA-B), and the quantitative insulin
      sensitivity check index (QUICKI) were calculated. Glucose tolerance abnormalities
      included impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and
      type 2 diabetes (T2DM). DII scores were positively associated with 2h-PG (beta =
      0.04; p = 0.05). There was no significant linear trend across quartiles of DII
      for adjusted means of glucose-insulin homeostasis markers. Participants in the
      highest quartile of DII score tended to have higher FPG compared to those in the
      second quartile of DII score (5.46 vs. 5.38 mmol/L, p = 0.07) and higher fasting
      insulin and HOMA-IR compared to those in the lowest quartile (8.52 vs. 8.12 uU/mL
      for fasting insulin, p = 0.07; 2.06 vs. 1.96 for HOMA-IR, p = 0.08). No
      significant associations were observed between DII and risk of IFG, IGT, T2DM,
      and insulin resistance. Among glucose-insulin homeostasis markers, DII had a
      positive weak association only with 2h-PG.

PMID- 27869718
TI  - Endocrine Dysfunction in Female FMR1 Premutation Carriers: Characteristics and
      Association with Ill Health.
AB  - Female FMR1 premutation carriers (PMC) have been suggested to be at greater risk
      of ill health, in particular endocrine dysfunction, compared to the general
      population. We set out to review the literature relating to endocrine
      dysfunction, including premature ovarian insufficiency (POI), in female PMCs, and
      then to consider whether endocrine dysfunction in itself may be predictive of
      other illnesses in female PMCs. A systematic review and pilot data from a semi
      structured health questionnaire were used. Medline, Embase, and PsycInfo were
      searched for papers concerning PMCs and endocrine dysfunction. For the pilot
      study, self-reported diagnoses in females were compared between PMCs with
      endocrine dysfunction (n = 18), PMCs without endocrine dysfunction (n = 14), and
      individuals without the premutation (n = 15). Twenty-nine papers were identified
      in the review; the majority concerned POI and reduced fertility, which are
      consistently found to be more common in PMCs than controls. There was some
      evidence that thyroid dysfunction may occur more frequently in subgroups of PMCs
      and that those with endocrine difficulties have poorer health than those without.
      In the pilot study, PMCs with endocrine problems reported higher levels of
      fibromyalgia (p = 0.03), tremor (p = 0.03), headache (p = 0.01) and obsessive
      compulsive disorder (p = 0.009) than either comparison group. Further larger
      scale research is warranted to determine whether female PMCs are at risk of
      endocrine disorders other than those associated with reproduction and whether
      endocrine dysfunction identifies a high-risk group for the presence of other
      health conditions.

PMID- 27869720
TI  - 30iemes Journees Franco-Belges de Pharmacochimie.
AB  - The "Journees Franco-Belges de Pharmacochimie" is a recognized annual meeting in
      organic and medicinal chemistry known for the quality of scientific exchange and
      conviviality. Young researchers were encouraged to present their work and share
      ideas with senior scientists. Abstracts of plenary lectures, oral communications,
      and posters presented during the meeting are collected in this report.

PMID- 27869721
TI  - The Benefit of Conserving and Gaining Resources after Trauma: A Systematic
      Review.
AB  - BACKGROUND: Traumatic events involve loss of resources, which has consistently
      been found to be associated with developing stress-related illness such as
      posttraumatic stress disorder (PTSD). OBJECTIVE: The purpose of this systematic
      literature review was to determine if there is evidence for the salutatory effect
      of resource gain on PTSD, and if there are intervention models that utilize and
      assess gain in PTSD. DATA SOURCES: All relevant online databases were
      systematically searched using key terms and a method, detailed in Figure 1.
      RESULTS: Of 22 relevant articles, there were three intervention studies, one
      longitudinal naturalistic study, eleven non-intervention association studies
      focusing on PTSD, and eight non-intervention association studies not focusing on
      PTSD. The intervention and naturalistic studies showed a significant positive
      effect on PTSD by specifically targeting the gain of resources during an
      intervention. Other non-intervention research supports the notion that resource
      loss is pathogenic and resource gain is beneficial after traumatic exposure.
      CONCLUSIONS: Interventions that develop and assess effects of gain of various
      types of resources on stress-related illness should be encouraged. Interventions
      that already have proven efficacy for PTSD might include standardized assessment
      of resource loss and gain to further understand mechanisms of action.

PMID- 27869722
TI  - Virtual Distances Methodology as Verification Technique for AACMMs with a
      Capacitive Sensor Based Indexed Metrology Platform.
AB  - This paper presents a new verification procedure for articulated arm coordinate
      measuring machines (AACMMs) together with a capacitive sensor-based indexed
      metrology platform (IMP) based on the generation of virtual reference distances.
      The novelty of this procedure lays on the possibility of creating virtual points,
      virtual gauges and virtual distances through the indexed metrology platform's
      mathematical model taking as a reference the measurements of a ball bar gauge
      located in a fixed position of the instrument's working volume. The measurements
      are carried out with the AACMM assembled on the IMP from the six rotating
      positions of the platform. In this way, an unlimited number and types of
      reference distances could be created without the need of using a physical gauge,
      therefore optimizing the testing time, the number of gauge positions and the
      space needed in the calibration and verification procedures. Four evaluation
      methods are presented to assess the volumetric performance of the AACMM. The
      results obtained proved the suitability of the virtual distances methodology as
      an alternative procedure for verification of AACMMs using the indexed metrology
      platform.

PMID- 27869719
TI  - Targeted Molecular Imaging in Adrenal Disease-An Emerging Role for Metomidate PET
      CT.
AB  - Adrenal lesions present a significant diagnostic burden for both radiologists and
      endocrinologists, especially with the increasing number of adrenal
      'incidentalomas' detected on modern computed tomography (CT) or magnetic
      resonance imaging (MRI). A key objective is the reliable distinction of benign
      disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or
      malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g.,
      bronchial, renal). Benign lesions may still be associated with adverse sequelae
      through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing's
      syndrome, phaeochromocytoma). Here, identifying a causative lesion, or
      lateralising the disease to a single adrenal gland, is key to effective
      management, as unilateral adrenalectomy may offer the potential for curing
      conditions that are typically associated with significant excess morbidity and
      mortality. This review considers the evolving role of positron emission
      tomography (PET) imaging in addressing the limitations of traditional cross
      sectional imaging and adjunctive techniques, such as venous sampling, in the
      management of adrenal disorders. We review the development of targeted molecular
      imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different
      radiolabeled metomidate compounds. Particular consideration is given to iodo
      metomidate PET tracers for the diagnosis and management of adrenocortical
      carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in
      primary aldosteronism.

PMID- 27869723
TI  - Quencher-Free Fluorescence Method for the Detection of Mercury(II) Based on
      Polymerase-Aided Photoinduced Electron Transfer Strategy.
AB  - A new quencher-free Hg2+ ion assay method was developed based on polymerase
      assisted photoinduced electron transfer (PIET). In this approach, a probe is
      designed with a mercury ion recognition sequence (MRS) that is composed of two T
      rich functional areas separated by a spacer of random bases at the 3'-end, and a
      sequence of stacked cytosines at the 5'-end, to which a fluorescein (FAM) is
      attached. Upon addition of Hg2+ ions into this sensing system, the MRS folds into
      a hairpin structure at the 3'-end with Hg2+-mediated base pairs. In the presence
      of DNA polymerase, it will catalyze the extension reaction, resulting in the
      formation of stacked guanines, which will instantly quench the fluorescence of
      FAM through PIET. Under optimal conditions, the limit of detection for Hg2+ ions
      was estimated to be 5 nM which is higher than the US Environmental Protection
      Agency (EPA) standard limit. In addition, no labeling with a quencher was
      requiring, and the present method is fairly simple, fast and low cost. It is
      expected that this cost-effective fluorescence method might hold considerable
      potential in the detection of Hg2+ ions in real biological and environmental
      samples.

PMID- 27869725
TI  - Wireless Mid-Infrared Spectroscopy Sensor Network for Automatic Carbon Dioxide
      Fertilization in a Greenhouse Environment.
AB  - In this paper, a wireless mid-infrared spectroscopy sensor network was designed
      and implemented for carbon dioxide fertilization in a greenhouse environment. A
      mid-infrared carbon dioxide (CO2) sensor based on non-dispersive infrared (NDIR)
      with the functionalities of wireless communication and anti-condensation
      prevention was realized as the sensor node. Smart transmission power regulation
      was applied in the wireless sensor network, according to the Received Signal
      Strength Indication (RSSI), to realize high communication stability and low-power
      consumption deployment. Besides real-time monitoring, this system also provides a
      CO2 control facility for manual and automatic control through a LabVIEW platform.
      According to simulations and field tests, the implemented sensor node has a
      satisfying anti-condensation ability and reliable measurement performance on CO2
      concentrations ranging from 30 ppm to 5000 ppm. As an application, based on the
      Fuzzy proportional, integral, and derivative (PID) algorithm realized on a
      LabVIEW platform, the CO2 concentration was regulated to some desired
      concentrations, such as 800 ppm and 1200 ppm, in 30 min with a controlled
      fluctuation of <+/-35 ppm in an acre of greenhouse.

PMID- 27869724
TI  - Mosquito Oviposition Behavior and Vector Control.
AB  - The burden of gene transfer from one mosquito generation to the next falls on the
      female and her eggs. The selection of an oviposition site that guarantees egg and
      larval survival is a critical step in the reproductive process. The dangers
      associated with ephemeral aquatic habitats, lengthy droughts, freezing winters,
      and the absence of larval nutrition makes careful oviposition site selection by a
      female mosquito extremely important. Mosquito species exhibit a remarkable
      diversity of oviposition behaviors that ensure eggs are deposited into
      microenvironments conducive for successful larval development and the emergence
      of the next mosquito generation. An understanding of mosquito oviposition
      behavior is necessary for the development of surveillance and control
      opportunities directed against specific disease vectors. For example, Aedes
      aegypti Linnaeus is the vector of viruses causing important human diseases
      including yellow fever, dengue, chikungunya, and Zika. The preference of this
      species to oviposit in natural and artificial containers has facilitated the
      development of Ae. aegypti-specific surveillance and toxic oviposition traps
      designed to detect and control this important vector species in and around
      disease foci. A better understanding of the wide diversity of mosquito
      oviposition behavior will allow the development of new and innovative
      surveillance and control devices directed against other important mosquito
      vectors of human and animal disease.

PMID- 27869726
TI  - Highly Sensitive and Practical Detection of Plant Viruses via Electrical
      Impedance of Droplets on Textured Silicon-Based Devices.
AB  - Early diagnosis of plant virus infections before the disease symptoms appearance
      may represent a significant benefit in limiting disease spread by a prompt
      application of appropriate containment steps. We propose a label-free procedure
      applied on a device structure where the electrical signal transduction is
      evaluated via impedance spectroscopy techniques. The device consists of a droplet
      suspension embedding two representative purified plant viruses i.e., Tomato
      mosaic virus and Turnip yellow mosaic virus, put in contact with a highly
      hydrophobic plasma textured silicon surface. Results show a high sensitivity of
      the system towards the virus particles with an interestingly low detection limit,
      from tens to hundreds of attomolar corresponding to pg/mL of sap, which refers,
      in the infection time-scale, to a concentration of virus particles in still
      symptomless plants. Such a threshold limit, together with an envisaged
      engineering of an easily manageable device, compared to more sophisticated
      apparatuses, may contribute in simplifying the in-field plant virus diagnostics.

PMID- 27869728
TI  - A Holistic Model of Care to Support Those Living with and beyond Cancer.
AB  - BACKGROUND: Globally, the burden of cancer continues to increase and it is well
      documented that while not a homogeneous population, cancer patients and cancer
      survivors face many physical, psychological, social, spiritual, and financial
      issues. Cancer care is shifting from a disease-focused to a patient-centered
      approach resulting in an increased need to address these concerns. METHODS:
      Utilizing a quality improvement approach, this paper describes an integrated
      cancer care model at Bloomhill Cancer Center (BCC) in Queensland, Australia that
      demonstrates the ability to meet the holistic needs of patients living with and
      beyond cancer and to identify opportunities for better practice and service
      provision. RESULTS: Survey results indicate that 67% and 77% of respondents were
      very satisfied and 27% and 17% were satisfied with their first contact and very
      satisfied with their first meeting with a nurse at BCC. Clients also reported
      being very satisfied (46%) or satisfied (30%) with the emotional support they
      received at BCC and over 90% were very satisfied or satisfied with the touch
      therapies that the received. CONCLUSION: Due to the early success of the
      interventions provided by BCC, the model potentially offers other states and
      countries a framework for supportive cancer care provision for people living with
      and beyond cancer.

PMID- 27869727
TI  - Respiratory Diseases in University Students Associated with Exposure to
      Residential Dampness or Mold.
AB  - University students are frequently exposed to residential dampness or mold (i.e.,
      visible mold, mold odor, dampness, or water leaks), a well-known contributor to
      asthma, allergic rhinitis, and respiratory infections. This study aims to: (a)
      describe the prevalence of these respiratory diseases among university students;
      and (b) examine the independent contribution of residential dampness or mold to
      these diseases. An online survey was conducted in March 2014 among the 26,676
      students registered at the Universite de Sherbrooke (Quebec, Canada). Validated
      questions and scores were used to assess self-reported respiratory diseases
      (i.e., asthma-like symptoms, allergic rhinitis, and respiratory infections),
      residential dampness or mold, and covariates (e.g., student characteristics).
      Using logistic regressions, the crude and adjusted odd ratios between residential
      dampness or mold and self-reported respiratory diseases were examined. Results
      from the participating students (n = 2097; response rate: 8.1%) showed high
      prevalence of allergic rhinitis (32.6%; 95% CI: 30.6-34.7), asthma-like symptoms
      (24.0%; 95% CI: 22.1-25.8) and respiratory infections (19.4%; 95% CI: 17.7-21.2).
      After adjustment, exposure to residential dampness or mold was associated with
      allergic rhinitis (OR: 1.25; 95% CI: 1.01-1.55) and asthma-like symptoms (OR:
      1.70; 95% CI: 1.37-2.11), but not with respiratory infections (OR: 1.07; 95% CI:
      0.85-1.36). Among symptomatic students, this exposure was also associated with
      uncontrolled and burdensome respiratory symptoms (p < 0.01). University students
      report a high prevalence of allergic rhinitis, asthma-like symptoms and
      respiratory infections. A common indoor hazard, residential dampness or mold, may
      play a role in increasing atopic respiratory diseases and their suboptimal
      control in young adults. These results emphasize the importance for public health
      organizations to tackle poor housing conditions, especially amongst university
      students who should be considered "at-risk".

PMID- 27869729
TI  - Auditing the Immunization Data Quality from Routine Reports in Shangyu District,
      East China.
AB  - Objective: To evaluate the immunization data quality in Shangyu District, East
      China. Methods: An audit for immunization data for the year 2014 was conducted in
      20 vaccination clinics of Shangyu District. The consistency of immunization data
      was estimated by verification factors (VFs), which was the proportion of vaccine
      doses reported as being administered that could be verified by written
      documentation at vaccination clinics. The quality of monitoring systems was
      evaluated using the quality index (QI). Results: The VFs of 20 vaccine doses
      ranged from 0.94 to 1.04 at the district level. The VFs for the 20 vaccination
      clinics ranged from 0.57 to 1.07. The VFs for Shangyu District was 0.98. The mean
      of total QI score of the 20 vaccination clinics was 80.32%. A significant
      correlation between the VFs of the 3rd dose of the diphtheria-tetanus-pertussis
      combined vaccine (DTP) and QI scores was observed at the vaccination clinic
      level. Conclusions: Deficiencies in data consistency and immunization reporting
      practice in Shangyu District were observed. Targeted measures are suggested to
      improve the quality of the immunization reporting system in vaccination clinics
      with poor data consistency.

PMID- 27869730
TI  - Context-Aware Fusion of RGB and Thermal Imagery for Traffic Monitoring.
AB  - In order to enable a robust 24-h monitoring of traffic under changing
      environmental conditions, it is beneficial to observe the traffic scene using
      several sensors, preferably from different modalities. To fully benefit from
      multi-modal sensor output, however, one must fuse the data. This paper introduces
      a new approach for fusing color RGB and thermal video streams by using not only
      the information from the videos themselves, but also the available contextual
      information of a scene. The contextual information is used to judge the quality
      of a particular modality and guides the fusion of two parallel segmentation
      pipelines of the RGB and thermal video streams. The potential of the proposed
      context-aware fusion is demonstrated by extensive tests of quantitative and
      qualitative characteristics on existing and novel video datasets and benchmarked
      against competing approaches to multi-modal fusion.

PMID- 27869731
TI  - Sensor for In-Motion Continuous 3D Shape Measurement Based on Dual Line-Scan
      Cameras.
AB  - The acquisition of three-dimensional surface data plays an increasingly important
      role in the industrial sector. Numerous 3D shape measurement techniques have been
      developed. However, there are still limitations and challenges in fast
      measurement of large-scale objects or high-speed moving objects. The innovative
      line scan technology opens up new potentialities owing to the ultra-high
      resolution and line rate. To this end, a sensor for in-motion continuous 3D shape
      measurement based on dual line-scan cameras is presented. In this paper, the
      principle and structure of the sensor are investigated. The image matching
      strategy is addressed and the matching error is analyzed. The sensor has been
      verified by experiments and high-quality results are obtained.

PMID- 27869732
TI  - Insect Gallers and Their Plant Hosts: From Omics Data to Systems Biology.
AB  - Gall-inducing insects are capable of exerting a high level of control over their
      hosts' cellular machinery to the extent that the plant's development, metabolism,
      chemistry, and physiology are all altered in favour of the insect. Many gallers
      are devastating pests in global agriculture and the limited understanding of
      their relationship with their hosts prevents the development of robust management
      strategies. Omics technologies are proving to be important tools in elucidating
      the mechanisms involved in the interaction as they facilitate analysis of plant
      hosts and insect effectors for which little or no prior knowledge exists. In this
      review, we examine the mechanisms behind insect gall development using evidence
      from omics-level approaches. The secretion of effector proteins and induced
      phytohormonal imbalances are highlighted as likely mechanisms involved in gall
      development. However, understanding how these components function within the
      system is far from complete and a number of questions need to be answered before
      this information can be used in the development of strategies to engineer or
      breed plants with enhanced resistance.

PMID- 27869734
TI  - Factors Affecting the Formation of 2:1 Host:Guest Inclusion Complexes of 2-[(R
      Phenyl)amine]-1,4-naphthalenediones (PAN) in beta- and gamma-Cyclodextrins.
AB  - The molecular hosts cyclodextrins form inclusion complexes with a wide variety of
      guests, resulting in complexes with various host:guest stoichiometries. In the
      case of a series of 19 1,4-naphthoquinolines as guests with either beta- or gamma
      cyclodextrin studied using electrospray mass spectroscopy, in most cases only 1:1
      complexes were observed, with 2:1 host:guest complexes observed in just 6 out of
      38 host:guest combinations. It is shown that these higher-order complexes were
      observed only in the case of small (or no) electronically withdrawing
      substituents, and were much less likely in the case of the larger gamma
      cyclodextrin host. The size and electronic properties of the substituents
      involved shows that both steric and electronic factors must be taken into account
      in predicting which cyclodextrin host:guest stoichiometries will be stable enough
      to form (or once formed, be robust enough to be observed in the ESI-MS
      experiments). It is clear that the prediction of host-guest stoichiometry for a
      specific host-guest pair is complicated, and involves a subtle interplay of both
      electronic and steric factors. However, there are definite trends, which can be
      used to help predict host:guest stoichiometry for a given host-guest pair.

PMID- 27869733
TI  - Antiviral Therapy by HIV-1 Broadly Neutralizing and Inhibitory Antibodies.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection causes acquired immune
      deficiency syndrome (AIDS), a global epidemic for more than three decades. HIV-1
      replication is primarily controlled through antiretroviral therapy (ART) but this
      treatment does not cure HIV-1 infection. Furthermore, there is increasing viral
      resistance to ART, and side effects associated with long-term therapy.
      Consequently, there is a need of alternative candidates for HIV-1 prevention and
      therapy. Recent advances have discovered multiple broadly neutralizing antibodies
      against HIV-1. In this review, we describe the key epitopes on the HIV-1 Env
      protein and the reciprocal broadly neutralizing antibodies, and discuss the
      ongoing clinical trials of broadly neutralizing and inhibitory antibody therapy
      as well as antibody combinations, bispecific antibodies, and methods that improve
      therapeutic efficacy by combining broadly neutralizing antibodies (bNAbs) with
      latency reversing agents. Compared with ART, HIV-1 therapeutics that incorporate
      these broadly neutralizing and inhibitory antibodies offer the advantage of
      decreasing virus load and clearing infected cells, which is a promising prospect
      in HIV-1 prevention and treatment.

PMID- 27869735
TI  - Low Expression of CAPON in Glioma Contributes to Cell Proliferation via the Akt
      Signaling Pathway.
AB  - CAPON is an adapter protein for nitric oxide synthase 1 (NOS1). CAPON has two
      isoforms in the human brain: CAPON-L (long form of CAPON) and CAPON-S (short form
      of CAPON). Recent studies have indicated the involvement of CAPON in
      tumorigenesis beyond its classical role in NOS1 activity regulation. In this
      study, we found that the protein levels of CAPON-S, but not than CAPON-L, were
      significantly decreased in glioma tissues. Therefore, we established lentivirus
      mediated stable cell lines with CAPON-S overexpression or down-regulation, and
      investigated the role of CAPON-S in the proliferation of glioma cells by using
      CCK8, EdU, and flow cytometry assays. Overexpression of CAPON-S reduced the cell
      variability and the percentage of EdU-positive cells, and arrested the cells in
      the G1 phase in glioma cells. Silencing of CAPON by short-hairpin RNA showed the
      opposite effects. Furthermore, an intracellular signaling array revealed that
      overexpression of CAPON-S resulted in a remarkable reduction in the
      phosphorylation of Akt and S6 ribosomal protein in glioma cells, which was
      further confirmed by Western blot. These findings suggest that CAPON may function
      as a tumor suppressor in human brain glioma and that the inactivation of the Akt
      signaling pathway caused by CAPON-S overexpression may provide insight into the
      underlying mechanism of CAPON in glioma cell proliferation.

PMID- 27869736
TI  - Circulating IL-27 Is Elevated in Rheumatoid Arthritis Patients.
AB  - Cytokines are key immunoregulatory molecules that regulate T lymphocyte-mediated
      immune responses and inflammatory reactions. We determined whether there is
      aberrant expression of interleukin-27 (IL-27) in rheumatoid arthritis (RA)
      patients and investigated the clinical significance of these changes. IL-27 is a
      key cellular factor that regulates the differentiation of CD4+ T cells, which can
      secrete interleukin-10 (IL-10) and interleukin-17 (IL-17) in vivo. Concentrations
      of serum IL-27 in 67 RA patients, and 36 sex- and age-matched control subjects
      were measured by enzyme-linked immunosorbent assay (ELISA). Results showed that
      concentrations of serum IL-27 in all RA patients were significantly higher than
      in healthy control subjects, and there was a significant and positive correlation
      between serum IL-27 levels and disease activity in all RA patients. Levels of
      serum IL-27 in RA patients were significantly correlated with disease activity
      score in 28 joints (DAS28). Moreover, immunosuppressive treatment with
      leflunomide downregulated the levels of IL-27 in active RA patients. Therefore,
      the elevated production of circulating T cell inflammatory factors contributes to
      the pathogenesis of RA, and serum IL-27 could potentially serve as a new
      biomarker of RA disease activity.

PMID- 27869738
TI  - Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine.
AB  - Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids
      and are broadly distributed in the plant kingdom. Many plants that contain RIPs
      are listed in the pharmacopoeias of folk medicine all over the world, mostly
      because of their toxicity. This review analyses the position occupied in
      traditional medicine by plants from which RIPs have been isolated. The overview
      starts from the antique age of the Mediterranean area with ancient Egypt,
      followed by the Greek and Roman classic period. Then, the ancient oriental
      civilizations of China and India are evaluated. More recently, Unani medicine and
      European folk medicine are examined. Finally, the African and American folk
      medicines are taken into consideration. In conclusion, a list of RIP-expressing
      plants, which have been used in folk medicine, is provided with the geographical
      distribution and the prescriptions that are recommended by traditional healers.
      Some final considerations are provided on the present utilization of such herbal
      treatments, both in developing and developed countries, often in the absence of
      scientific validation. The most promising prospect for the medicinal use of RIP
      expressing plants is the conjugation of purified RIPs to antibodies that
      recognise tumour antigens for cancer therapy.

PMID- 27869737
TI  - Toosendanin Exerts an Anti-Cancer Effect in Glioblastoma by Inducing Estrogen
      Receptor beta- and p53-Mediated Apoptosis.
AB  - Glioblastoma (GBM) is the most common primary brain tumor with median survival of
      approximately one year. This dismal poor prognosis is due to resistance to
      currently available chemotherapeutics; therefore, new cytotoxic agents are
      urgently needed. In the present study, we reported the cytotoxicity of
      toosendanin (TSN) in the GBM U87 and C6 cell lines in vitro and in vivo. By using
      the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide)
      assay, flow cytometry analysis, and Western blot, we found that TSN inhibited U87
      and C6 cell proliferation and induced apoptosis at a concentration as low as 10
      nM. Administration of TSN also reduced tumor burden in a xenograft model of
      athymic nude mice. Pharmacological and molecular studies suggested that estrogen
      receptor beta (ERbeta) and p53 were prominent targets for TSN. GBM cell apoptosis
      induced by TSN was a stepwise biological event involving the upregulation of
      ERbeta and contextual activation of functional p53. Collectively, our study
      indicates, for the first time, that TSN is a candidate of novel anti-cancer drugs
      for GBM. Furthermore, ERbeta and p53 could act as predictive biomarkers for the
      sensitivity of cancer to TSN.

PMID- 27869739
TI  - Perinatal Risk Factors and Genu Valgum Conducive to the Onset of Growing Pains in
      Early Childhood.
AB  - The most prevalent musculoskeletal disorder of childhood with unclear aetiology
      is growing pains (GPs). Anatomic deformities and factors that change bone
      turnover are implicated in GP pathophysiology. Perinatal risk factors alter the
      bone metabolism affecting the bone mineral density and content. The aim of our
      study was to analyze the relationship between GPs, knock knees and perinatal
      factors. The examined population consisted of 276 children aged 3-7 years. Among
      them, ten pairs of dizygotic twins were evaluated. The data were collected by
      using a combination of semi-structured questionnaires, clinical examinations and
      medical charts of the children and the obstetric history of the mothers. A total
      of 78 children presenting GPs met Peterson's criteria. Genu valgum severity was a
      significant factor for GP manifestation and for their increased frequency and
      intensity. Subsequently, perinatal factors regarding gestational age, Apgar
      score, head circumference (lower than 33 cm) and birth length or weight (smaller
      than 50 cm and 3000 g, respectively) made a remarkable contribution to the
      development of GPs. Conversely, antenatal corticosteroid treatment, increased
      maternal age and maternal smoking during pregnancy were not predictive of the
      disorder. Our data are potentially supportive for the "bone strength" theory and
      for the contribution of anatomical disturbances in GP appearance.

PMID- 27869740
TI  - Functional Role of the C-Terminal Amphipathic Helix 8 of Olfactory Receptors and
      Other G Protein-Coupled Receptors.
AB  - G protein-coupled receptors (GPCRs) transduce various extracellular signals, such
      as neurotransmitters, hormones, light, and odorous chemicals, into intracellular
      signals via G protein activation during neurological, cardiovascular, sensory and
      reproductive signaling. Common and unique features of interactions between GPCRs
      and specific G proteins are important for structure-based design of drugs in
      order to treat GPCR-related diseases. Atomic resolution structures of GPCR
      complexes with G proteins have revealed shared and extensive interactions between
      the conserved DRY motif and other residues in transmembrane domains 3 (TM3), 5
      and 6, and the target G protein C-terminal region. However, the initial
      interactions formed between GPCRs and their specific G proteins remain unclear.
      Alanine scanning mutagenesis of the murine olfactory receptor S6 (mOR-S6)
      indicated that the N-terminal acidic residue of helix 8 of mOR-S6 is responsible
      for initial transient and specific interactions with chimeric Galpha15_olf,
      resulting in a response that is 2.2-fold more rapid and 1.7-fold more robust than
      the interaction with Galpha15. Our mutagenesis analysis indicates that the
      hydrophobic core buried between helix 8 and TM1-2 of mOR-S6 is important for the
      activation of both Galpha15_olf and Galpha15. This review focuses on the
      functional role of the C-terminal amphipathic helix 8 based on several recent
      GPCR studies.

PMID- 27869743
TI  - A Metal-Free Regioselective Multicomponent Approach for the Synthesis of Free
      Radical Scavenging Pyrimido-Fused Indazoles and Their Fluorescence Studies.
AB  - This study deals with a new and efficient metal-free regioselective synthesis of
      pyrimido-fused indazoles with nitrogen ring junction motifs. We have developed a
      metal-free domino type reaction between 3-aminoindazole, aryl aldehydes and
      aceotophenones in the presence of KOH/DMF that leads to pyrimido[1,2-b]indazole
      analogues. Response Surface Methodology (RSM) coupled with a Box-Behnken design
      (BBD) were utilized for exploring the effect of base used (A), temperature of
      reaction (B) and (C), reaction time. This approach can allow access to a variety
      of pyrimidoindazole fluorophores and related compounds. The compound N,N-dimethyl
      4-(2-phenylpyrimido[1,2-b]indazol-4-yl)aniline (4e) displays the maximum
      fluorescence intensity at 518 nm and shows a fluorescence quantum yield of 0.068.
      The synthesized pyramido-fused indazoles have been evaluated for their free
      radical scavenging activity and compound 4f showed good antioxidant activity.

PMID- 27869742
TI  - Design, Synthesis and Structure-Activity Relationships of Novel Diaryl Urea
      Derivatives as Potential EGFR Inhibitors.
AB  - Two novel series of diaryl urea derivatives 5a-i and 13a-l were synthesized and
      evaluated for their cytotoxicity against H-460, HT-29, A549, and MDA-MB-231
      cancer cell lines in vitro. Therein, 4-aminoquinazolinyl-diaryl urea derivatives
      5a-i demonstrated significant activity, and seven of them are more active than
      sorafenib, with IC50 values ranging from 0.089 to 5.46 MUM. Especially, compound
      5a exhibited the most active potency both in cellular (IC50 = 0.15, 0.089, 0.36,
      and 0.75 MUM, respectively) and enzymatic assay (IC50 = 56 nM against EGFR),
      representing a promising lead for further optimization.

PMID- 27869745
TI  - Many Activities, One Structure: Functional Plasticity of Ribozyme Folds.
AB  - Catalytic RNAs, or ribozymes, are involved in a number of essential biological
      processes, such as replication of RNA genomes and mobile genetic elements, RNA
      splicing, translation, and RNA degradation. The function of ribozymes requires
      the formation of active sites decorated with RNA functional groups within defined
      three-dimensional (3D) structures. The genotype (sequence) of RNAs ultimately
      determines what 3D structures they adopt (as a function of their environmental
      conditions). These 3D structures, in turn, give rise to biochemical activity,
      which can further elaborate them by catalytic rearrangements or association with
      other molecules. The fitness landscape of a non-periodic linear polymer, such as
      RNA, relates its primary structure to a phenotype. Two major challenges in the
      analysis of ribozymes is to map all possible genotypes to their corresponding
      catalytic activity (that is, to determine their fitness landscape
      experimentally), and to understand whether their genotypes and three-dimensional
      structures can support multiple different catalytic functions. Recently, the
      combined results of experiments that employ in vitro evolution methods, high
      throughput sequencing and crystallographic structure determination have hinted at
      answers to these two questions: while the fitness landscape of ribozymes is
      rugged, meaning that their catalytic activity cannot be optimized by a smooth
      trajectory in sequence space, once an RNA achieves a stable three-dimensional
      fold, it can be endowed with distinctly different biochemical activities through
      small changes in genotype. This functional plasticity of highly structured RNAs
      may be particularly advantageous for the adaptation of organisms to drastic
      changes in selective pressure, or for the development of new biotechnological
      tools.

PMID- 27869741
TI  - Isoliquiritigenin Attenuates Atherogenesis in Apolipoprotein E-Deficient Mice.
AB  - Isoliquiritigenin (ISL) exhibits antioxidation and anti-inflammation activity. We
      sought to investigate the effects and mechanism of ISL on the development of
      atherosclerotic lesions in apolipoprotein E-deficient (apoE-/-) mice. Firstly, we
      determined that ISL reduced the mRNA levels of inflammatory factors interleukin 6
      (IL-6), tumor necrosis factor alpha (TNF-alpha), and monocyte chemotactic protein
      1 (MCP-1), while it increased the expression of several lipoprotein-related genes
      in peritoneal macrophages treated with lipopolysaccharide (LPS). ISL also
      enhanced peroxisome proliferator-activated receptor gamma (PPARgamma) protein
      levels and reversed the changes of ATP-binding cassette transporter A (ABCA1) and
      cluster of differentiation 36 (CD36) in macrophages treated with oxidative low
      density lipoprotein (ox-LDL). Then, in an in vivo study, female apoE-/- mice were
      fed a Western diet with ISL (0, 20, 100 mg/kg/day) added for 12 weeks. We found
      that ISL decreased the plasma cholesterol levels of very low-density lipoprotein
      (VLDL)/LDL, promoted plasma superoxide dismutase (SOD) and paraoxonase-1 (PON1)
      activities, and decreased plasma IL-6, TNF-alpha, and MCP-1 levels. Moreover, ISL
      significantly reduced the atherosclerotic lesions and hepatic steatosis in apoE-/
      mice. In the liver, ISL altered the expression of several key genes (such as
      SRBI, ABCA1, ABCG8, PPARgamma, and FASN) involving cholesterol-selective uptake
      and excretion into bile, triglyceride (TG) biosynthesis, and inflammation. These
      results suggest that the atheroprotective effects of ISL are due to the
      improvement of lipid metabolism, antioxidation, and anti-inflammation, which
      involve PPARgamma-dependent signaling.

PMID- 27869744
TI  - Protective Effect of Tempol against Cisplatin-Induced Ototoxicity.
AB  - One of the major adverse effects of cisplatin chemotherapy is hearing loss.
      Cisplatin-induced ototoxicity hampers treatment because it often necessitates
      dose reduction, which decreases cisplatin efficacy. This study was performed to
      investigate the effect of Tempol on cisplatin-induced ototoxicity in an auditory
      cell line, House Ear Institute-Organ of Corti 1 (HEI-OC1). Cultured HEI-OC1 cells
      were exposed to 30 MUM cisplatin for 24 h with or without a 2 h pre-treatment
      with Tempol. Cell viability was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay and apoptotic cells were identified using
      terminal deoxynucleotidyl transferase dUTP nick end labeling of nuclei (TUNEL)
      assay and flow cytometry. The effects of Tempol on cisplatin-induced cleaved
      poly(ADP-ribose) polymerase, cleaved caspase, and mitochondrial inducible nitric
      oxide synthase expression were evaluated using western blot analysis. Levels of
      intracellular reactive oxygen species (ROS) were measured to assess the effects
      of Tempol on cisplatin-induced ROS accumulation. Mitochondria were evaluated by
      confocal microscopy, and the mitochondrial membrane potential was measured to
      investigate whether Tempol protected against cisplatin-induced mitochondrial
      dysfunction. Cisplatin treatment decreased cell viability, and increased
      apoptotic features and markers, ROS accumulation, and mitochondrial dysfunction.
      Tempol pre-treatment before cisplatin exposure significantly inhibited all these
      cisplatin-induced effects. These results demonstrate that Tempol inhibits
      cisplatin-induced cytotoxicity in HEI-OC1, and could play a preventive role
      against cisplatin-induced ototoxicity.

PMID- 27869746
TI  - Dew Point Calibration System Using a Quartz Crystal Sensor with a Differential
      Frequency Method.
AB  - In this paper, the influence of temperature on quartz crystal microbalance (QCM)
      sensor response during dew point calibration is investigated. The aim is to
      present a compensation method to eliminate temperature impact on frequency
      acquisition. A new sensitive structure is proposed with double QCMs. One is kept
      in contact with the environment, whereas the other is not exposed to the
      atmosphere. There is a thermal conductivity silicone pad between each crystal and
      a refrigeration device to keep a uniform temperature condition. A differential
      frequency method is described in detail and is applied to calibrate the frequency
      characteristics of QCM at the dew point of -3.75  degrees C. It is worth noting
      that frequency changes of two QCMs were approximately opposite when temperature
      conditions were changed simultaneously. The results from continuous experiments
      show that the frequencies of two QCMs as the dew point moment was reached have
      strong consistency and high repeatability, leading to the conclusion that the
      sensitive structure can calibrate dew points with high reliability.

PMID- 27869747
TI  - The Vitamin E Analog Gamma-Tocotrienol (GT3) and Statins Synergistically Up
      Regulate Endothelial Thrombomodulin (TM).
AB  - Statins; a class of routinely prescribed cholesterol-lowering drugs; inhibit 3
      hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) and strongly induce
      endothelial thrombomodulin (TM); which is known to have anti-inflammatory; anti
      coagulation; anti-oxidant; and radioprotective properties. However; high-dose
      toxicity limits the clinical use of statins. The vitamin E family member gamma
      tocotrienol (GT3) also suppresses HMGCR activity and induces TM expression
      without causing significant adverse side effects; even at high concentrations. To
      investigate the synergistic effect of statins and GT3 on TM; a low dose of
      atorvastatin and GT3 was used to treat human primary endothelial cells. Protein
      level TM expression was measured by flow cytometry. TM functional activity was
      determined by activated protein C (APC) generation assay. Expression of Kruppel
      like factor 2 (KLF2), one of the key transcription factors of TM, was measured by
      quantitative reverse transcription polymerase chain reaction (qRT-PCR). TM
      expression increased in a dose-dependent manner after both atorvastatin and GT3
      treatment. A combined treatment of a low-dose of atorvastatin and GT3
      synergistically up-regulated TM expression and functional activity. Finally;
      atorvastatin and GT3 synergistically increased KLF2 expression. These findings
      suggest that combined treatment of statins with GT3 may provide significant
      health benefits in treating a number of pathophysiological conditions; including
      inflammatory and cardiovascular diseases.

PMID- 27869749
TI  - Ultrasound-Assisted Extraction May Not Be a Better Alternative Approach than
      Conventional Boiling for Extracting Polysaccharides from Herbal Medicines.
AB  - In clinical practice polysaccharides from herbal medicines are conventionally
      prepared by boiling water extraction (BWE), while ultrasound-assisted extraction
      (UAE) has often been used instead employed in laboratory research due to its
      strong extraction ability and efficiency. However, if and how the polysaccharides
      obtained by UAE and BWE are comparable, and hence whether the UAE-based research
      is instructive for the actual usage of herbal polysaccharides still requires
      further evaluation. To address this issue, here we chemically analyzed and
      compared the UAE- and BWE-obtained polysaccharides from three herbal medicines,
      i.e., Ginseng Radix, Astragali Radix and Dendrobii Officinalis Caulis. Then, the
      spike recovery of two series of standard dextran and pullulan by UAE and BWE was
      tested. The results showed that the polysaccharides from the herbal medicines by
      UAE were quantitatively and qualitatively different with those by BWE. The
      powerful extraction ability and polysaccharide degradation caused by ultrasound
      collectively contributed to these differences. It was then revealed that not only
      the UAE conditions but also the polysaccharide structures could affect the
      extraction ability and polysaccharide degradation. Given these, we highly
      recommended that the effects of UAE on polysaccharides from herbal medicines
      should be first carefully considered before employing it in relevant chemical and
      pharmacological analysis.

PMID- 27869748
TI  - Design of New Antibacterial Enhancers Based on AcrB's Structure and the
      Evaluation of Their Antibacterial Enhancement Activity.
AB  - Previously, artesunate (AS) and dihydroartemisinine 7 (DHA7) were found to have
      antibacterial enhancement activity against Escherichia coli via inhibition of the
      efflux pump AcrB. However, they were only effective against E. coli standard
      strains. This study aimed to develop effective antibacterial enhancers based on
      the previous work. Our results demonstrate that 86 new antibacterial enhancers
      were designed via 3D-SAR and molecular docking. Among them, DHA27 had the best
      antibacterial enhancement activity. It could potentiate the antibacterial effects
      of ampicillin against not only E. coli standard strain but also clinical strains,
      and of beta-lactam antibiotics, not non-beta-lactamantibiotics. DHA27 could
      increase the accumulation of daunomycin and nile red within E. coli ATCC 35218,
      but did not increase the bacterial membrane permeability. DHA27 reduced acrB's
      mRNA expression of E. coli ATCC 35218 in a dose-dependent manner, and its
      antibacterial enhancement activity is related to the degree of acrB mRNA
      expression in E. coli clinical strains. The polypeptides from AcrB were obtained
      via molecular docking assay; the pre-incubated polypeptides could inhibit the
      activity of DHA27. Importantly, DHA27 had no cytotoxicity on cell proliferation.
      In conclusion, among newly designed antibacterial enhancers, DHA27 had favorable
      physical and pharmacological properties with no significant cytotoxicity at
      effective concentrations, and might serve as a potential efflux pump inhibitor in
      the future.

PMID- 27869750
TI  - Biophysical Approach to Mechanisms of Cancer Prevention and Treatment with Green
      Tea Catechins.
AB  - Green tea catechin and green tea extract are now recognized as non-toxic cancer
      preventives for humans. We first review our brief historical development of green
      tea cancer prevention. Based on exciting evidence that green tea catechin, (-)
      epigallocatechin gallate (EGCG) in drinking water inhibited lung metastasis of
      B16 melanoma cells, we and other researchers have studied the inhibitory
      mechanisms of metastasis with green tea catechins using biomechanical tools,
      atomic force microscopy (AFM) and microfluidic optical stretcher. Specifically,
      determination of biophysical properties of cancer cells, low cell stiffness, and
      high deformability in relation to migration, along with biophysical effects, were
      studied by treatment with green tea catechins. The study with AFM revealed that
      low average values of Young's moduli, indicating low cell stiffness, are closely
      associated with strong potential of cell migration and metastasis for various
      cancer cells. It is important to note that treatments with EGCG and green tea
      extract elevated the average values of Young's moduli resulting in increased
      stiffness (large elasticity) of melanomas and various cancer cells. We discuss
      here the biophysical basis of multifunctions of green tea catechins and green tea
      extract leading to beneficial effects for cancer prevention and treatment.

PMID- 27869751
TI  - Effects of Power Ultrasound on Stability of Cyanidin-3-glucoside Obtained from
      Blueberry.
AB  - Power ultrasound (US) could potentially be used in the food industry in the
      future. However, the extent of anthocyanin degradation by US requires
      investigation. Cyanidin-3-glucoside (Cy-3-glu) obtained from blueberry extracts
      was used as research material to investigate the effect of power ultrasound on
      food processing of anthocyanin-rich raw materials. The effects of ultrasonic
      waves on the stability of Cy-3-glu and on the corresponding changes in UV-Vis
      spectrum and antioxidant activity were investigated, and the mechanisms of
      anthocyanin degradation induced by ultrasonic waves were discussed. To explore Cy
      3-glu degradation in different environments, we kept the Cy-3-glu solution
      treated with ultrasonic waves in four concentrations (0%, 10%, 20%, and 50%) of
      ethanol aqueous solutions to simulate water, beer, wine, and liquor storage
      environment according to the chemical kinetics method. Results show that the
      basic spectral characteristics of Cy-3-glu did not significantly change after
      power ultrasound cell crusher application at 30  degrees C. However, with
      anthocyanin degradation, the intensity of the peak for Cy-3-glu at 504 nm
      significantly decreased (p < 0.05). The degradation kinetics of Cy-3-glu by
      ultrasonic waves (200-500 W frequency) fitted well to first-order reaction
      kinetics, and the degradation rate constant of Cy-3-glu under power ultrasound
      was considerably larger than that under thermal degradation (p < 0.05). The
      sensitivity of the anthocyanins of blueberry to temperature increased with
      increasing ethanol concentration, and the longest half-life was observed in 20%
      ethanol aqueous solution.

PMID- 27869752
TI  - Extracting Plant Phenology Metrics in a Great Basin Watershed: Methods and
      Considerations for Quantifying Phenophases in a Cold Desert.
AB  - Plant phenology is recognized as important for ecological dynamics. There has
      been a recent advent of phenology and camera networks worldwide. The established
      PhenoCam Network has sites in the United States, including the western states.
      However, there is a paucity of published research from semi-arid regions. In this
      study, we demonstrate the utility of camera-based repeat digital imagery and use
      of R statistical phenopix package to quantify plant phenology and phenophases in
      four plant communities in the semi-arid cold desert region of the Great Basin. We
      developed an automated variable snow/night filter for removing ephemeral snow
      events, which allowed fitting of phenophases with a double logistic algorithm. We
      were able to detect low amplitude seasonal variation in pinyon and juniper
      canopies and sagebrush steppe, and characterize wet and mesic meadows in area
      averaged analyses. We used individual pixel-based spatial analyses to separate
      sagebrush shrub canopy pixels from interspace by determining differences in
      phenophases of sagebrush relative to interspace. The ability to monitor plant
      phenology with camera-based images fills spatial and temporal gaps in remotely
      sensed data and field based surveys, allowing species level relationships between
      environmental variables and phenology to be developed on a fine time scale thus
      providing powerful new tools for land management.

PMID- 27869753
TI  - Identification and Expression Analysis of Polygalacturonase Family Members during
      Peach Fruit Softening.
AB  - Polygalacturonase (PG) is an important hydrolytic enzyme involved in pectin
      degradation during fruit softening. However, the roles of PG family members in
      fruit softening remain unclear. We identified 45 PpPG genes in the peach genome
      which are clustered into six subclasses. PpPGs consist of four to nine exons and
      three to eight introns, and the exon/intron structure is basically conserved in
      all but subclass E. Only 16 PpPG genes were expressed in ripening fruit, and
      their expression profiles were analyzed during storage in two peach cultivars
      with different softening characteristics. Eight PGs (PpPG1, -10, -12, -13, -15, 
      23, -21, and -22) in fast-softening "Qian Jian Bai" (QJB) fruit and three PGs
      (PpPG15, -21, and -22) in slow-softening "Qin Wang" (QW) fruit exhibited
      softening-associated patterns; which also were affected by ethylene treatment.
      Our results suggest that the different softening characters in QW and QJB fruit
      is related to the amount of PG members. While keeping relatively lower levels
      during QW fruit softening, the expression of six PGs (PpPG1, -10, -12, -11, -14,
      and -35) rapidly induced by ethylene. PpPG24, -25 and -38 may not be involved in
      softening of peach fruit.

PMID- 27869755
TI  - Distribution of Type I Restriction-Modification Systems in Streptococcus suis: An
      Outlook.
AB  - Streptococcus suis is a porcine commensal and pathogen with zoonotic potential.
      We recently identified a novel Type I restriction-modification (R-M) system in a
      zoonotic S. suis clone which has emerged in the Netherlands. Here, we describe
      the DNA inversions in the specificity subunit of this system in S. suis serotype
      2, clonal complex 20 and explain the absence of domain movement by the absence of
      repeats. In addition, we identified a core Type I R-M system present in 95% of
      the isolates and found an association of the distribution of Type I R-M systems
      in the S. suis genome with population structure. We speculate on the potential
      role of Type I R-M systems in S. suis given the recently described associations
      of Type I R-M systems with virulence and propose future research directions.

PMID- 27869754
TI  - A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole.
AB  - The present study aimed to compare pharmacokinetic parameters of two pramipexole
      0.25 mg formulations in order to show bioequivalence. The study was conducted in
      a randomized, open-label, two-period, two-sequence, and crossover design,
      involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole
      evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia,
      the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG,
      Ingelheim am Rhein, Germany. All eligible subjects were required to fast before
      each drug administration period, which was separated by a one-week washout
      period. Pramipexole concentrations in plasma were assayed using a validated ultra
      performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector.
      The evaluated pharmacokinetic parameters included the area under the plasma
      concentration curve from time zero to the last observed measurable concentration
      (AUC0-t), the area under the plasma concentration curve extrapolated to infinite
      time (AUC0-infinity), the maximum plasma concentration (Cmax), the time to reach
      Cmax (tmax), and the plasma concentration half-life (t1/2). To evaluate the
      bioequivalence of those two pramipexole formulations, 90% confidence intervals
      (CIs) for geometric mean ratios of both formulations were calculated for AUC and
      Cmax parameters, while tmax and t1/2 differences were analyzed on the non
      transformed data using Wilcoxon matched-pairs and a Student's paired t-test,
      respectively. The 90% CIs for the geometric mean ratios of the two pramipexole
      formulations were 95.89% (90.73%-101.34%), 95.53% (89.75%-101.68%), and 92.11%
      (84.35%-100.58%) for AUC0-t, AUC0-infinity, and Cmax, respectively. There were no
      statistically significant differences for tmax and t1/2 between the two
      pramipexole formulations. It is concluded that two pramipexole formulations in
      this study were bioequivalent.

PMID- 27869756
TI  - A Review of Temperature, pH, and Other Factors that Influence the Survival of
      Salmonella in Mayonnaise and Other Raw Egg Products.
AB  - Salmonellosis is one of the main causes of foodborne illnesses worldwide, with
      outbreaks predominately linked to contamination of eggs and raw egg products,
      such as mayonnaise. This review explores previous studies that have investigated
      Salmonella control mechanisms utilized in the production of raw egg mayonnaise
      and other food products. Apart from the use of pasteurized eggs, the main control
      mechanism identified is the pH of the raw egg products, which plays an important
      role in the consistency and stability while affecting the survival of Salmonella
      spp. However, currently there is no consensus regarding the critical pH limit for
      the control of Salmonella. The effectiveness of pH as a control mechanism is
      influenced by the type of acid used, with the effectiveness of lemon juice
      compared with vinegar highly debated. Additionally, Salmonella susceptibility to
      pH stresses may also be influenced by storage temperature (in some studies
      refrigeration temperatures protected Salmonella spp. from acidulants) and is
      further complicated by the development of Salmonella cross-tolerance-induced
      responses, pH homeostasis achieved by the cellular antiport and symport systems,
      and acid tolerance response (ATR). These mechanisms all provide Salmonella with
      an added advantage to ensure survival under various pH conditions. Other
      confounding factors include the fat content, and the addition of NaCl, garlic and
      plant essential oils (PEOs) from mint, cinnamon, cardamom and clove.

PMID- 27869757
TI  - Clostridium perfringens Sialidases: Potential Contributors to Intestinal
      Pathogenesis and Therapeutic Targets.
AB  - Clostridium perfringens is a major cause of histotoxic and intestinal infections
      of humans and other animals. This Gram-positive anaerobic bacterium can produce
      up to three sialidases named NanH, NanI, and NanJ. The role of sialidases in
      histotoxic infections, such as gas gangrene (clostridial myonecrosis), remains
      equivocal. However, recent in vitro studies suggest that NanI may contribute to
      intestinal virulence by upregulating production of some toxins associated with
      intestinal infection, increasing the binding and activity of some of those
      toxins, and enhancing adherence of C. perfringens to intestinal cells. Possible
      contributions of NanI to intestinal colonization are further supported by
      observations that the C. perfringens strains causing acute food poisoning in
      humans often lack the nanI gene, while other C. perfringens strains causing
      chronic intestinal infections in humans usually carry a nanI gene. Certain
      sialidase inhibitors have been shown to block NanI activity and reduce C.
      perfringens adherence to cultured enterocyte-like cells, opening the possibility
      that sialidase inhibitors could be useful therapeutics against C. perfringens
      intestinal infections. These initial in vitro observations should be tested for
      their in vivo significance using animal models of intestinal infections.

PMID- 27869758
TI  - The Impact of Rurality and Disadvantage on the Diagnostic Interval for Breast
      Cancer in a Large Population-Based Study of 3202 Women in Queensland, Australia.
AB  - Delays in diagnosing breast cancer (BC) can lead to poorer outcomes. We
      investigated factors related to the diagnostic interval in a population-based
      cohort of 3202 women diagnosed with BC in Queensland, Australia. Interviews
      ascertained method of detection and dates of medical/procedural appointments, and
      clinical information was obtained from medical records. Time intervals were
      calculated from self-recognition of symptoms (symptom-detected) or mammogram
      (screen-detected) to diagnosis (diagnostic interval (DI)). The cohort included
      1560 women with symptom-detected and 1642 with screen-detected BC. Symptom
      detected women had higher odds of DI of >60 days if they were Indigenous (OR =
      3.12, 95% CI = 1.40, 6.98); lived in outer regional (OR = 1.50, 95% CI = 1.09,
      2.06) or remote locations (OR = 2.46, 95% CI = 1.39, 4.38); or presented with a
      "non-lump" symptom (OR = 1.84, 95% CI = 1.43, 2.36). For screen-detected BC,
      women who were Indigenous (OR = 2.36, 95% CI = 1.03, 5.80); lived in remote
      locations (OR = 2.35, 95% CI = 1.24, 4.44); or disadvantaged areas (OR = 1.69,
      95% CI = 1.17, 2.43) and attended a public screening facility (OR = 2.10, 95% CI
      = 1.40, 3.17) had higher odds of DI > 30 days. Our study indicates a disadvantage
      in terms of DI for rural, disadvantaged and Indigenous women. Difficulties in
      accessing primary care and diagnostic services are evident. There is a need to
      identify and implement an efficient and effective model of care to minimize
      avoidable longer diagnostic intervals.

PMID- 27869760
TI  - Spotlight on the Underdogs-An Analysis of Underrepresented Alternaria Mycotoxins
      Formed Depending on Varying Substrate, Time and Temperature Conditions.
AB  - Alternaria (A.) is a genus of widespread fungi capable of producing numerous,
      possibly health-endangering Alternaria toxins (ATs), which are usually not the
      focus of attention. The formation of ATs depends on the species and complex
      interactions of various environmental factors and is not fully understood. In
      this study the influence of temperature (7  degrees C, 25  degrees C), substrate
      (rice, wheat kernels) and incubation time (4, 7, and 14 days) on the production
      of thirteen ATs and three sulfoconjugated ATs by three different Alternaria
      isolates from the species groups A. tenuissima and A. infectoria was determined.
      High-performance liquid chromatography coupled with tandem mass spectrometry was
      used for quantification. Under nearly all conditions, tenuazonic acid was the
      most extensively produced toxin. At 25  degrees C and with increasing incubation
      time all toxins were formed in high amounts by the two A. tenuissima strains on
      both substrates with comparable mycotoxin profiles. However, for some of the
      toxins, stagnation or a decrease in production was observed from day 7 to 14. As
      opposed to the A. tenuissima strains, the A. infectoria strain only produced low
      amounts of ATs, but high concentrations of stemphyltoxin III. The results provide
      an essential insight into the quantitative in vitro AT formation under different
      environmental conditions, potentially transferable to different field and storage
      conditions.

PMID- 27869759
TI  - A Cell Biological Perspective on Past, Present and Future Investigations of the
      Spindle Assembly Checkpoint.
AB  - The spindle assembly checkpoint (SAC) is a quality control mechanism that ensures
      accurate chromosome segregation during cell division. It consists of a
      mechanochemical signal transduction mechanism that senses the attachment of
      chromosomes to the spindle, and a signaling cascade that inhibits cell division
      if one or more chromosomes are not attached. Extensive investigations of both
      these component systems of the SAC have synthesized a comprehensive understanding
      of the underlying molecular mechanisms. This review recounts the milestone
      results that elucidated the SAC, compiles a simple model of the complex molecular
      machinery underlying the SAC, and highlights poorly understood facets of the
      biochemical design and cell biological operation of the SAC that will drive
      research forward in the near future.

PMID- 27869761
TI  - Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated
      Intestinal Porcine Epithelial Cells (IPEC-J2).
AB  - The human, animal and plant pathogen Fusarium, which contaminates agricultural
      commodities worldwide, produces numerous secondary metabolites. An example is the
      thoroughly-investigated deoxynivalenol (DON), which severely impairs
      gastrointestinal barrier integrity. However, to date, the toxicological profile
      of other Fusarium-derived metabolites, such as enniatins, beauvericin,
      moniliformin, apicidin, aurofusarin, rubrofusarin, equisetin and bikaverin, are
      poorly characterized. Thus we examined their effects-as metabolites alone and as
      metabolites in combination with DON-on the intestinal barrier function of
      differentiated intestinal porcine epithelial cells (IPEC-J2) over 72 h.
      Transepithelial electrical resistance (TEER) was measured at 24-h intervals,
      followed by evaluation of cell viability using neutral red (NR) assay. Enniatins
      A, A1, B and B1, apicidin, aurofusarin and beauvericin significantly reduced
      TEER. Moniliformin, equisetin, bikaverin and rubrofusarin had no effect on TEER.
      In the case of apicidin, aurofusarin and beauvericin, TEER reductions were
      further substantiated by the addition of otherwise no-effect DON concentrations.
      In all cases, viability was unaffected, confirming that TEER reductions were not
      due to compromised viability. Considering the prevalence of mycotoxin
      contamination and the diseases associated with intestinal barrier disruption,
      consumption of contaminated food or feed may have substantial health
      implications.

PMID- 27869765
TI  - Localization of CO2 Leakage from a Circular Hole on a Flat-Surface Structure
      Using a Circular Acoustic Emission Sensor Array.
AB  - Leak localization is essential for the safety and maintenance of storage vessels.
      This study proposes a novel circular acoustic emission sensor array to realize
      the continuous CO2 leak localization from a circular hole on the surface of a
      large storage vessel in a carbon capture and storage system. Advantages of the
      proposed array are analyzed and compared with the common sparse arrays.
      Experiments were carried out on a laboratory-scale stainless steel plate and leak
      signals were obtained from a circular hole in the center of this flat-surface
      structure. In order to reduce the influence of the ambient noise and dispersion
      of the acoustic wave on the localization accuracy, ensemble empirical mode
      decomposition is deployed to extract the useful leak signal. The time differences
      between the signals from the adjacent sensors in the array are calculated through
      correlation signal processing before estimating the corresponding distance
      differences between the sensors. A hyperbolic positioning algorithm is used to
      identify the location of the circular leak hole. Results show that the circular
      sensor array has very good directivity toward the circular leak hole.
      Furthermore, an optimized method is proposed by changing the position of the
      circular sensor array on the flat-surface structure or adding another circular
      sensor array to identify the direction of the circular leak hole. Experiential
      results obtained on a 100 cm * 100 cm stainless steel plate demonstrate that the
      full-scale error in the leak localization is within 0.6%.

PMID- 27869764
TI  - Drivers' Visual Search Patterns during Overtaking Maneuvers on Freeway.
AB  - Drivers gather traffic information primarily by means of their vision. Especially
      during complicated maneuvers, such as overtaking, they need to perceive a variety
      of characteristics including the lateral and longitudinal distances with other
      vehicles, the speed of others vehicles, lane occupancy, and so on, to avoid
      crashes. The primary object of this study is to examine the appropriate visual
      search patterns during overtaking maneuvers on freeways. We designed a series of
      driving simulating experiments in which the type and speed of the leading vehicle
      were considered as two influential factors. One hundred and forty participants
      took part in the study. The participants overtook the leading vehicles just like
      they would usually do so, and their eye movements were collected by use of the
      Eye Tracker. The results show that participants' gaze durations and saccade
      durations followed normal distribution patterns and that saccade angles followed
      a log-normal distribution pattern. It was observed that the type of leading
      vehicle significantly impacted the drivers' gaze duration and gaze frequency. As
      the speed of a leading vehicle increased, subjects' saccade durations became
      longer and saccade angles became larger. In addition, the initial and destination
      lanes were found to be key areas with the highest visual allocating proportion,
      accounting for more than 65% of total visual allocation. Subjects tended to more
      frequently shift their viewpoints between the initial lane and destination lane
      in order to search for crucial traffic information. However, they seldom directly
      shifted their viewpoints between the two wing mirrors.

PMID- 27869763
TI  - Crash Risk Prediction Modeling Based on the Traffic Conflict Technique and a
      Microscopic Simulation for Freeway Interchange Merging Areas.
AB  - This paper evaluates the traffic safety of freeway interchange merging areas
      based on the traffic conflict technique. The hourly composite risk indexes (HCRI)
      was defined. By the use of unmanned aerial vehicle (UAV) photography and video
      processing techniques, the conflict type and severity was judged. Time to
      collision (TTC) was determined with the traffic conflict evaluation index. Then,
      the TTC severity threshold was determined. Quantizing the weight of the conflict
      by direct losses of different severities of freeway traffic accidents, the
      calculated weight of the HCRI can be obtained. Calibration of the relevant
      parameters of the micro-simulation simulator VISSIM is conducted by the travel
      time according to the field data. Variables are placed into orthogonal tables at
      different levels. On the basis of this table, the trajectory file of every
      traffic condition is simulated, and then submitted into a surrogate safety
      assessment model (SSAM), identifying the number of hourly traffic conflicts in
      the merging area, a statistic of HCRI. Moreover, the multivariate linear
      regression model was presented and validated to study the relationship between
      HCRI and the influencing variables. A comparison between the HCRI model and the
      hourly conflicts ratio (HCR), without weight, shows that the HCRI model fitting
      degree was obviously higher than the HCR. This will be a reference to design and
      implement operational planners.

PMID- 27869762
TI  - Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2
      Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of
      Prospective Cohort Studies.
AB  - The epidemiological evidence for a dose-response relationship between magnesium
      intake and risk of type 2 diabetes mellitus (T2D) is sparse. The aim of the study
      was to summarize the evidence for the association of dietary magnesium intake
      with risk of T2D and evaluate the dose-response relationship. We conducted a
      systematic review and meta-analysis of prospective cohort studies that reported
      dietary magnesium intake and risk of incident T2D. We identified relevant studies
      by searching major scientific literature databases and grey literature resources
      from their inception to February 2016. We included cohort studies that provided
      risk ratios, i.e., relative risks (RRs), odds ratios (ORs) or hazard ratios
      (HRs), for T2D. Linear dose-response relationships were assessed using random
      effects meta-regression. Potential nonlinear associations were evaluated using
      restricted cubic splines. A total of 25 studies met the eligibility criteria.
      These studies comprised 637,922 individuals including 26,828 with a T2D
      diagnosis. Compared with the lowest magnesium consumption group in the
      population, the risk of T2D was reduced by 17% across all the studies; 19% in
      women and 16% in men. A statistically significant linear dose-response
      relationship was found between incremental magnesium intake and T2D risk. After
      adjusting for age and body mass index, the risk of T2D incidence was reduced by
      8%-13% for per 100 mg/day increment in dietary magnesium intake. There was no
      evidence to support a nonlinear dose-response relationship between dietary
      magnesium intake and T2D risk. The combined data supports a role for magnesium in
      reducing risk of T2D, with a statistically significant linear dose-response
      pattern within the reference dose range of dietary intake among Asian and US
      populations. The evidence from Europe and black people is limited and more
      prospective studies are needed for the two subgroups.

PMID- 27869766
TI  - Supporting Teens with Chronic Pain to Obtain High School Credits: Chronic Pain 35
      in Alberta.
AB  - Chronic pain is a significant problem in children and teens, and adolescents with
      chronic pain often struggle to attend school on a regular basis. We present in
      this article a novel program we developed that integrates attendance at a group
      cognitive-behavioural chronic pain self-management program with earning high
      school credits. We collaborated with Alberta Education in the development of this
      course, Chronic Pain 35. Adolescents who choose to enroll are invited to
      demonstrate their scientific knowledge related to pain, understanding of and
      engagement with treatment homework, and demonstrate their creativity by
      completing a project, which demonstrates at least one concept. Integrating
      Chronic Pain 35 into an adolescent's academic achievements is a creative strategy
      that facilitates the engagement of adolescents in learning and adopting pain
      coping techniques. It also helps teens to advocate for themselves in the school
      environment and improve their parents' and teachers' understanding of adolescent
      chronic pain. This is one of the first successful collaborations between a
      pediatric health program and provincial education leaders, aimed at integrating
      learning and obtaining school credit for learning about and engaging in health
      self-management for teens. The authors hope this paper serves as an effective
      reference model for any future collaborating programs aimed at supporting teens
      with chronic pain to obtain high school credits.

PMID- 27869767
TI  - Clinical Decision-Making in the Treatment of Schizophrenia: Focus on Long-Acting
      Injectable Antipsychotics.
AB  - The purpose of this study was to identify clinician characteristics associated
      with higher prescription rates of long-acting injectable (LAI) antipsychotics, as
      well as the sources that influence medical decision-making regarding the
      treatment of schizophrenia. We surveyed 202 psychiatrists during six regional
      French conferences (Bordeaux, Lyon, Marseille, Nice, Paris, and Strasbourg). Data
      on the characteristics of practice, prescription rates of antipsychotic, and
      information sources about their clinical decisions were collected. Most
      psychiatrists used second-generation antipsychotics (SGAs), and preferentially an
      oral formulation, in the treatment of schizophrenia. LAI SGAs were prescribed to
      30.4% of schizophrenic patients. The duration and type of practice did not
      influence the class or formulation of antipsychotics used. The clinicians
      following the higher percentage of schizophrenic patients were associated with a
      higher use of LAI antipsychotics and a lower use of oral SGAs. Personal
      experience, government regulatory approval, and guidelines for the treatment of
      schizophrenia were the three main contributing factors guiding clinicians'
      decision-making regarding the treatment of schizophrenia. The more clinicians
      follow schizophrenic patients, the more they use LAI antipsychotics. The
      development of specialized programs with top specialists should lead to better
      use of LAI antipsychotics in the treatment of schizophrenia.

PMID- 27869768
TI  - Synthesis of Non-Toxic Silica Particles Stabilized by Molecular Complex Oleic
      Acid/Sodium Oleate.
AB  - The present work is focused on the preparation of biocompatible silica particles
      from sodium silicate, stabilized by a vesicular system containing oleic acid
      (OLA) and its alkaline salt (OLANa). Silica nanoparticles were generated by the
      partial neutralization of oleic acid (OLA), with the sodium cation present in the
      aqueous solutions of sodium silicate. At the molar ratio OLA/Na+ = 2:1, the molar
      ratio (OLA/OLANa = 1:1) required to form vesicles, in which the carboxyl and
      carboxylate groups have equal concentrations, was achieved. In order to obtain
      hydrophobically modified silica particles, octadecyltriethoxysilane (ODTES) was
      added in a sodium silicate sol-gel mixture at different molar ratios. The
      interactions between the octadecyl groups from the modified silica and the oleyl
      chains from the OLA/OLANa stabilizing system were investigated via simultaneous
      thermogravimetry (TG) and differential scanning calorimetry (DSC) (TG-DSC)
      analyses.A significant decrease in vaporization enthalpy and an increase in
      amount of ODTES were observed. Additionally, that the hydrophobic interaction
      between OLA and ODTES has a strong impact on the hybrids' final morphology and on
      their textural characteristics was revealed. The highest hydrodynamic average
      diameter and the most negative zeta potential were recorded for the hybrid in
      which the ODTES/sodium silicate molar ratio was 1:5. The obtained mesoporous
      silica particles, stabilized by the OLA/OLANa vesicular system, may find
      application as carriers for hydrophobic bioactive molecules.

PMID- 27869770
TI  - Direct Separation of Pregabalin Enantiomers Using a Zwitterionic Chiral Selector
      by High Performance Liquid Chromatography Coupled to Mass Spectrometry and
      Ultraviolet Detection.
AB  - The chromatographic resolution of pregabalin enantiomers has been often achieved
      by derivatization of the molecule, in order to reach enough sensitivity at low
      concentrations of the minor enantiomer present in the active principle. In the
      present article, the development and optimization of two liquid chromatographic
      methods are presented for the direct resolution of pregabalin enantiomers on a
      chiral stationary phase (CSP) containing a zwitterionic selector derived from
      cinchona alkaloid and sulfonic acid (CHIRALPAK ZWIX). The key parameters for the
      separation as well as the compatibility of chromatographic conditions with
      different detection modes (ultraviolet and mass spectrometry) were investigated.
      The resulting methods were found to be selective, of high performance and low
      limits of detection (2 ug/mL by UV and 1 ng/mL by MS, respectively) and
      quantification (6 ug/mL by UV and 5 ng/mL by MS, respectively) for the minor
      enantiomer which is considered as a chiral impurity.

PMID- 27869771
TI  - Selenium Nanoparticles Attenuate Oxidative Stress and Testicular Damage in
      Streptozotocin-Induced Diabetic Rats.
AB  - We investigated the protective and antioxidative effects of selenium
      nanoparticles (SeNPs) in streptozotocin STZ-induced diabetic rats. STZ-diabetic
      rats were exposed daily to treatments with SeNPs and/or insulin and then the
      effect of these treatments on the parameters correlated to oxidative damage of
      the rat testes were assessed. Biochemical analysis revealed that SeNPs are able
      to ameliorate the reduction in the serum testosterone caused by STZ-induced
      diabetes. Furthermore, SeNPs could significantly decrease testicular tissue
      oxidative stress markers, namely lipid peroxidation and nitric oxide. In
      contrast, treatment of the STZ-diabetic rats with SeNPs increased the glutathione
      content and antioxidant enzyme activities in testicular tissues. Moreover,
      microscopic analysis proved that SeNPs are able to prevent histological damage in
      the testes of STZ-diabetic rats. Molecular analysis revealed that the mRNA level
      of Bcl-2 (B-cell lymphoma 2) is significantly upregulated. On the contrary, the
      mRNA level of Bax (Bcl-2 Associated X Protein) was significantly downregulated.
      Furthermore, treatment of STZ-diabetic rats with SeNPs led to an elevation in the
      expression of PCNA (Proliferating Cell Nuclear Antigen Gene). Interestingly, the
      insulin treatment also exhibited a significant improvement in the testicular
      function in STZ-diabetic rats. Collectively, our results demonstrated the
      possible effects of SeNPs in attenuating diabetes-induced oxidative damage, in
      particular in testicular tissue.

PMID- 27869769
TI  - Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and
      Function.
AB  - The rapid progress in medicine, agriculture, and allied sciences has enabled the
      development of a large amount of potentially useful bioactive compounds, such as
      drugs and pesticides. However, there is another side of this phenomenon, which
      includes side effects and environmental pollution. To avoid or minimize the
      uncontrollable consequences of using the newly developed compounds, researchers
      seek a quick and effective means of their evaluation. In achieving this goal, the
      zebrafish (Danio rerio) has proven to be a highly useful tool, mostly because of
      its fast growth and development, as well as the ability to absorb the molecules
      diluted in water through its skin and gills. In this review, we focus on the
      reports concerning the application of zebrafish as a model for assessing the
      impact of toxicants on skeletal muscles, which share many structural and
      functional similarities among vertebrates, including zebrafish and humans.

PMID- 27869772
TI  - Aphis Glycines Virus 2, a Novel Insect Virus with a Unique Genome Structure.
AB  - The invasive soybean aphid, Aphis glycines, is a major pest in soybeans,
      resulting in substantial economic loss. We analyzed the A. glycines transcriptome
      to identify sequences derived from viruses of A. glycines. We identified
      sequences derived from a novel virus named Aphis glycines virus 2 (ApGlV2). The
      assembled virus genome sequence was confirmed by reverse transcription polymerase
      chain reaction (RT-PCR) and Sanger sequencing, conserved domains were
      characterized, and distribution, and transmission examined. This virus has a
      positive sense, single-stranded RNA genome of ~4850 nt that encodes three
      proteins. The RNA-dependent RNA polymerase (RdRp) of ApGlV2 is a permuted RdRp
      similar to those of some tetraviruses, while the capsid protein is structurally
      similar to the capsid proteins of plant sobemoviruses. ApGlV2 also encodes a
      larger minor capsid protein, which is translated by a readthrough mechanism.
      ApGlV2 appears to be widespread in A. glycines populations and to persistently
      infect aphids with a 100% vertical transmission rate. ApGlV2 is susceptible to
      the antiviral RNA interference (RNAi) pathway. This virus, with its unique genome
      structure with both plant- and insect-virus characteristics, is of particular
      interest from an evolutionary standpoint.

PMID- 27869774
TI  - Performance Evaluation of Proximal Sensors for Soil Assessment in Smallholder
      Farms in Embu County, Kenya.
AB  - Four proximal soil sensors were tested at four smallholder farms in Embu County,
      Kenya: a portable X-ray fluorescence sensor (PXRF), a mobile phone application
      for soil color determination by photography, a dual-depth electromagnetic
      induction (EMI) sensor, and a LED-based soil optical reflectance sensor.
      Measurements were made at 32-43 locations at each site. Topsoil samples were
      analyzed for plant-available nutrients (N, P, K, Mg, Ca, S, B, Mn, Zn, Cu, and
      Fe), pH, total nitrogen (TN) and total carbon (TC), soil texture, cation exchange
      capacity (CEC), and exchangeable aluminum (Al). Multivariate prediction models of
      each of the lab-analyzed soil properties were parameterized for 576 sensor
      variable combinations. Prediction models for K, N, Ca and S, B, Zn, Mn, Fe, TC,
      Al, and CEC met the setup criteria for functional, robust, and accurate models.
      The PXRF sensor was the sensor most often included in successful models. We
      concluded that the combination of a PXRF and a portable soil reflectance sensor
      is a promising combination of handheld soil sensors for the development of in
      situ soil assessments as a field-based alternative or complement to laboratory
      measurements.

PMID- 27869773
TI  - Neighborhood Characteristics: Influences on Pain and Physical Function in Youth
      at Risk for Chronic Pain.
AB  - Neighborhood features such as community socioeconomic status, recreational
      facilities, and parks have been correlated to the health outcomes of the
      residents living within those neighborhoods, especially with regard to health
      related quality of life, body mass index, and physical activity. The interplay
      between one's built environment and one's perceptions may affect physical health,
      well-being, and pain experiences. In the current study, neighborhood
      characteristics and attitudes about physical activity were examined in a high
      risk (youths with a parent with chronic pain) and low-risk (youths without a
      parent with chronic pain) adolescent sample. There were significant differences
      in neighborhood characteristics between the high-risk (n = 62) and low-risk (n =
      77) samples (ages 11-15), with low-risk participants living in residences with
      more walkability, closer proximity to parks, and higher proportion of
      neighborhood residents having college degrees. Results indicate that neighborhood
      features (e.g., walkability and proximity to parks), as well as positive
      attitudes about physical activity were correlated with lower levels of pain and
      pain-related disability, and higher performance in physical functioning tests.
      These findings suggest that the built environment may contribute to pain outcomes
      in youth, above and beyond the influence of family history of pain.

PMID- 27869775
TI  - Plant Virus Infection and the Ubiquitin Proteasome Machinery: Arms Race along the
      Endoplasmic Reticulum.
AB  - The endoplasmic reticulum (ER) is central to plant virus replication,
      translation, maturation, and egress. Ubiquitin modification of ER associated
      cellular and viral proteins, alongside the actions of the 26S proteasome, are
      vital for the regulation of infection. Viruses can arrogate ER associated
      ubiquitination as well as cytosolic ubiquitin ligases with the purpose of
      directing the ubiquitin proteasome system (UPS) to new targets. Such targets
      include necessary modification of viral proteins which may stabilize certain
      complexes, or modification of Argonaute to suppress gene silencing. The UPS
      machinery also contributes to the regulation of effector triggered immunity
      pattern recognition receptor immunity. Combining the results of unrelated
      studies, many positive strand RNA plant viruses appear to interact with cytosolic
      Ub-ligases to provide novel avenues for controlling the deleterious consequences
      of disease. Viral interactions with the UPS serve to regulate virus infection in
      a manner that promotes replication and movement, but also modulates the levels of
      RNA accumulation to ensure successful biotrophic interactions. In other
      instances, the UPS plays a central role in cellular immunity. These opposing
      roles are made evident by contrasting studies where knockout mutations in the UPS
      can either hamper viruses or lead to more aggressive diseases. Understanding how
      viruses manipulate ER associated post-translational machineries to better manage
      virus-host interactions will provide new targets for crop improvement.

PMID- 27869776
TI  - Complementary Feeding Strategies to Facilitate Acceptance of Fruits and
      Vegetables: A Narrative Review of the Literature.
AB  - Complementary feeding (CF), which should begin after exclusive breastfeeding for
      six months, according to the World Health Organization (WHO), or after four
      months and before six months according to the European Society for Pediatric
      Gastroenterology Hepatology and Nutrition (ESPGHAN), is a period when the infant
      implicitly learns what, when, how, and how much to eat. At the onset of CF, the
      brain and the gut are still developing and maturing, and food experiences
      contribute to shaping brain connections involved in food hedonics and in the
      control of food intake. These learning processes are likely to have a long-term
      impact. Children's consumption of fruit and vegetables (FV) is below
      recommendations in many countries. Thus, it is crucial to establish preferences
      for FV early, when infants are learning to eat. The development of food
      preferences mainly starts when infants discover their first solid foods. This
      narrative review summarizes the factors that influence FV acceptance at the start
      of the CF period: previous milk feeding experience; timing of onset of CF;
      repeated exposures to the food; variety of foods offered as of the start of the
      CF period; quality and sensory properties of the complementary foods; quality of
      the meal time context; and parental responsive feeding.

PMID- 27869778
TI  - Agarose and Its Derivatives as Supports for Enzyme Immobilization.
AB  - Agarose is a polysaccharide obtained from some seaweeds, with a quite particular
      structure that allows spontaneous gelation. Agarose-based beads are highly
      porous, mechanically resistant, chemically and physically inert, and sharply
      hydrophilic. These features-that could be further improved by means of covalent
      cross-linking-render them particularly suitable for enzyme immobilization with a
      wide range of derivatization methods taking advantage of chemical modification of
      a fraction of the polymer hydroxyls. The main properties of the polymer are
      described here, followed by a review of cross-linking and derivatization methods.
      Some recent, innovative procedures to optimize the catalytic activity and
      operational stability of the obtained preparations are also described, together
      with multi-enzyme immobilized systems and the main guidelines to exploit their
      performances.

PMID- 27869777
TI  - The Effects of Mild Gestational Hyperglycemia on Exclusive Breastfeeding
      Cessation.
AB  - Gestational diabetes increases the risk of a range of adverse perinatal outcomes,
      including breastfeeding failure, but the best cut-off point for gestational
      diabetes is unknown. The purpose of this study was to evaluate the association
      between mild gestational glucose tolerance impairment and the early cessation of
      exclusive breastfeeding (EBF). This is an observational study of 768 women with
      full term pregnancies that were screened for gestational diabetes at 24-28 weeks
      gestation. Subjects were divided into two groups: those with a normal 1-h glucose
      challenge test and those with an elevated 1-h glucose challenge test but still
      did not qualify for gestational diabetes. We constructed multivariable logistic
      regression models using data from 616 women with normal gestational glucose
      tolerance and 152 women with an isolated positive 1-h glucose challenge test. The
      risk of early exclusive breastfeeding cessation was found to increase in women
      with mildly impaired glucose tolerance during pregnancy (adjusted OR, 1.65; 95%
      CI: 1.11, 2.45). Risks of early EBF cessation were also independently associated
      with the amount of neonatal weight loss and admission to the neonatal ward.
      Instead, parity was associated with a decreased risk for shorter EBF duration.
      Insulin resistance-even in the absence of gestational diabetes mellitus-may be an
      impeding factor for EBF.

PMID- 27869780
TI  - The Parent Psychological Flexibility Questionnaire (PPFQ): Item Reduction and
      Validation in a Clinical Sample of Swedish Parents of Children with Chronic Pain.
AB  - In pediatric chronic pain, research indicates a positive relation between
      parental psychological flexibility (i.e., the parent's willingness to experience
      distress related to the child's pain in the service of valued behavior) and level
      of functioning in the child. This points to the utility of targeting parental
      psychological flexibility in pediatric chronic pain. The Parent Psychological
      Flexibility Questionnaire (PPFQ) is currently the only instrument developed for
      this purpose, and two previous studies have indicated its reliability and
      validity. The current study sought to validate the Swedish version of the 17-item
      PPFQ (PPFQ-17) in a sample of parents (n = 263) of children with chronic pain.
      Factor structure and internal reliability were evaluated by means of principal
      component analysis (PCA) and Cronbach's alpha. Concurrent criterion validity was
      examined by hierarchical multiple regression analyses with parental anxiety and
      depression as outcomes. The PCA supported a three-factor solution with 10 items
      explaining 69.5% of the total variance. Cronbach's alpha (0.86) indicated good
      internal consistency. The 10-item PPFQ (PPFQ-10) further explained a significant
      amount of variance in anxiety (29%), and depression (35.6%), confirming
      concurrent validity. In conclusion, results support the reliability and validity
      of the PPFQ-10, and suggest its usefulness in assessing psychological flexibility
      in parents of children with chronic pain.

PMID- 27869781
TI  - Molecular Docking Optimization in the Context of Multi-Drug Resistant and
      Sensitive EGFR Mutants.
AB  - The human Epidermal Growth Factor (EGFR) plays an important role in signaling
      pathways, such as cell proliferation and migration. Mutations like G719S, L858R,
      T790M, G719S/T790M or T790M/L858R can alter its conformation, and, therefore,
      drug responses from lung cancer patients. In this context, candidate drugs are
      being tested and in silico studies are necessary to know how these mutations
      affect the ligand binding site. This problem can be tackled by using a multi
      objective approach applied to the molecular docking problem. According to the
      literature, few studies are related to the application of multi-objective
      approaches by minimizing two or more objectives in drug discovery. In this study,
      we have used four algorithms (NSGA-II, GDE3, SMPSO and MOEA/D) to minimize two
      objectives: the ligand-receptor intermolecular energy and the RMSD score. We have
      prepared a set of instances that includes the wild-type EGFR kinase domain and
      the same receptor with somatic mutations, and then we assessed the performance of
      the algorithms by applying a quality indicator to evaluate the convergence and
      diversity of the reference fronts. The MOEA/D algorithm yields the best solutions
      to these docking problems. The obtained solutions were analyzed, showing
      promising results to predict candidate EGFR inhibitors by using this multi
      objective approach.

PMID- 27869782
TI  - Semisynthetic and SAR Studies of Amide Derivatives of Neocrotocembraneic Acid as
      Potential Antitumor Agents.
AB  - A series of novel amide derivatives of cembranoid neocrotocembraneic acid were
      designed and synthesized. The antiproliferative activities of these derivatives
      were evaluated against three human tumor cell lines (the human cervical cancer
      cell line HeLa, chronic myeloid leukemia cell line K562 and leukemia multidrug
      resistant cell line K562/A02). Some of the synthesized compounds exhibited
      moderate to good activity against all three cancer cell lines. Particularly,
      compound 8a exhibited more potent antiproliferative activity than the reference
      drug etoposide against drug-resistant cell line K562/A02, indicating that it
      possessed a great potential for further development as a multidrug resistance
      modulator by structural modification.

PMID- 27869779
TI  - Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and
      the Tumor Microenvironment.
AB  - The tumor suppressor p53 is the most frequently mutated gene in human cancers.
      Most of the mutations are missense leading to loss of p53 function in inducing
      apoptosis and senescence. In addition to these autonomous effects of p53
      inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53
      mutation/inactivation also leads to gain-of-function or activation of non
      autonomous pathways, which either directly or indirectly promote tumorigenesis.
      Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor
      inflammation and serves as an immunological gain-of-function driver of
      tumorigenesis via skewing immune landscape of the tumor microenvironment (TME).
      It is now increasingly appreciated that p53 dysfunction in various cellular
      compartments of the TME leads to immunosuppression and immune evasion. Although
      our understanding of the cellular and molecular processes that link p53 activity
      to host immune regulation is still incomplete, it is clear that
      activating/reactivating the p53 pathway in the TME also represents a compelling
      immunological strategy to reverse immunosuppression and enhance antitumor
      immunity. Here, we review our current understanding of the potential cellular and
      molecular mechanisms by which p53 participates in immune regulation and discuss
      how targeting the p53 pathway can be exploited to alter the immunological
      landscape of tumors for maximizing therapeutic outcome.

PMID- 27869784
TI  - Phytochemical Profiling of Flavonoids, Phenolic Acids, Terpenoids, and Volatile
      Fraction of a Rosemary (Rosmarinus officinalis L.) Extract.
AB  - This paper presents a comprehensive analysis of the phytochemical profile of a
      proprietary rosemary (Rosmarinus officinalis L.) extract rich in carnosic acid. A
      characterization of the (poly)phenolic and volatile fractions of the extract was
      carried out using mass spectrometric techniques. The (poly)phenolic composition
      was assessed by ultra-high performance liquid chromatography-electrospray
      ionization-mass spectrometry (UHPLC-ESI-MSn) and a total of 57 compounds were
      tentatively identified and quantified, 14 of these being detected in rosemary
      extract for the first time. The rosemary extract contained 24 flavonoids (mainly
      flavones, although flavonols and flavanones were also detected), 5 phenolic
      acids, 24 diterpenoids (carnosic acid, carnosol, and rosmanol derivatives), 1
      triterpenoid (betulinic acid), and 3 lignans (medioresinol derivatives). Carnosic
      acid was the predominant phenolic compound. The volatile profile of the rosemary
      extract was evaluated by head space solid-phase microextraction (HS-SPME) linked
      to gas chromatography-mass spectrometry (GC-MS). Sixty-three volatile molecules
      (mainly terpenes, alcohols, esters, aldehydes, and ketones) were identified. This
      characterization extends the current knowledge on the phytochemistry of
      Rosmarinus officinalis and is, to our knowledge, the broadest profiling of its
      secondary metabolites to date. It can assist in the authentication of rosemary
      extracts or rosemary-containing products or in testing its bioactivity. Moreover,
      this methodological approach could be applied to the study of other plant-based
      food ingredients.

PMID- 27869783
TI  - Comparative Analysis of RNAi-Based Methods to Down-Regulate Expression of Two
      Genes Expressed at Different Levels in Myzus persicae.
AB  - With the increasing availability of aphid genomic data, it is necessary to
      develop robust functional validation methods to evaluate the role of specific
      aphid genes. This work represents the first study in which five different
      techniques, all based on RNA interference and on oral acquisition of double
      stranded RNA (dsRNA), were developed to silence two genes, ALY and Eph,
      potentially involved in polerovirus transmission by aphids. Efficient silencing
      of only Eph transcripts, which are less abundant than those of ALY, could be
      achieved by feeding aphids on transgenic Arabidopsis thaliana expressing an RNA
      hairpin targeting Eph, on Nicotiana benthamiana infected with a Tobacco rattle
      virus (TRV)-Eph recombinant virus, or on in vitro-synthesized Eph-targeting
      dsRNA. These experiments showed that the silencing efficiency may differ greatly
      between genes and that aphid gut cells seem to be preferentially affected by the
      silencing mechanism after oral acquisition of dsRNA. In addition, the use of
      plants infected with recombinant TRV proved to be a promising technique to
      silence aphid genes as it does not require plant transformation. This work
      highlights the need to pursue development of innovative strategies to
      reproducibly achieve reduction of expression of aphid genes.

PMID- 27869786
TI  - A role for leucoanthocyanidin reductase in the extension of proanthocyanidins.
AB  - Proanthocyanidins (PAs) are the second most abundant plant polyphenolic compounds
      after lignin. PAs affect taste, mouth feel and astringency of many fruits, wines
      and beverages1,2, have been associated with reduced risks of cardiovascular
      disease, cancer and Alzheimer's disease3-5, can improve nutrition and prevent
      bloat in ruminant animals6 and enhance soil nitrogen retention7. PAs are
      oligomers and polymers of flavan-3-ols, primarily (-)-epicatechin and (+)
      catechin, but the mechanism by which the monomers polymerize and become insoluble
      is currently unknown. Leucoanthocyanidin reductase (LAR) has been shown to
      convert leucocyanidin to (+)-catechin8,9. Here, we report that loss of function
      of LAR in the model legume Medicago truncatula leads unexpectedly to loss of
      soluble epicatechin-derived PAs, increased levels of insoluble PAs, and
      accumulation of 4beta-(S-cysteinyl)-epicatechin, which provides the 4->8 linked
      extension units during non-enzymatic PA polymerization. LAR converts 4beta-(S
      cysteinyl)-epicatechin back to epicatechin, the starter unit in PAs, thereby
      regulating the relative proportions of starter and extension units and
      consequently the degree of PA oligomerization.

PMID- 27869785
TI  - Classic IL-6R signalling is dispensable for intestinal epithelial proliferation
      and repair.
AB  - Inflammatory bowel disease is characterized by disturbed cytokine signalling in
      the mucosa. Inhibition of the proinflammatory interleukin (IL)-6 pathway is a
      promising new therapeutic strategy, but safety concerns arise as IL-6 signalling
      also contributes to epithelial repair of the intestinal mucosa. To which extent
      IL-6 classic or trans-signalling contributes to intestinal repair remains
      elusive. We tested the influence of IL-6 classic signalling on intestinal repair
      and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic
      cancer cell lines, primary non-malignant intestinal organoids did not respond to
      IL-6 classic signalling. Mice deficient in intestinal IL-6R (IL-6RDeltaIEC mice)
      did not display increased susceptibility to acute dextran sulfate sodium (DSS)
      induced colitis. In the azoxymethane DSS model IL-6RDeltaIEC mice were not
      protected from inflammation-induced carcinogenesis but showed comparable tumor
      load to wild-type mice. These data indicate that classic signalling is not the
      major pathway to transduce IL-6 stimuli into the intestinal epithelium.

PMID- 27869787
TI  - Obligate plant farming by a specialized ant.
AB  - Many epiphytic plants have associated with ants to gain nutrients. Here, we
      report a novel type of ant-plant symbiosis in Fiji where one ant species actively
      and exclusively plants the seeds and fertilizes the seedlings of six species of
      Squamellaria (Rubiaceae). Comparison with related facultative ant plants suggests
      that such farming plays a key role in mutualism stability by mitigating the
      critical re-establishment step.

PMID- 27869788
TI  - Systems biology: A new CAM era.

PMID- 27869789
TI  - Genome-guided design of a defined mouse microbiota that confers colonization
      resistance against Salmonella enterica serovar Typhimurium.
AB  - Protection against enteric infections, also termed colonization resistance,
      results from mutualistic interactions of the host and its indigenous microbes.
      The gut microbiota of humans and mice is highly diverse and it is therefore
      challenging to assign specific properties to its individual members. Here, we
      have used a collection of murine bacterial strains and a modular design approach
      to create a minimal bacterial community that, once established in germ-free mice,
      provided colonization resistance against the human enteric pathogen Salmonella
      enterica serovar Typhimurium (S. Tm). Initially, a community of 12 strains,
      termed Oligo-Mouse-Microbiota (Oligo-MM12), representing members of the major
      bacterial phyla in the murine gut, was selected. This community was stable over
      consecutive mouse generations and provided colonization resistance against S. Tm
      infection, albeit not to the degree of a conventional complex microbiota.
      Comparative (meta)genome analyses identified functions represented in a
      conventional microbiome but absent from the Oligo-MM12. By genome-informed
      design, we created an improved version of the Oligo-MM community harbouring three
      facultative anaerobic bacteria from the mouse intestinal bacterial collection
      (miBC) that provided conventional-like colonization resistance. In conclusion, we
      have established a highly versatile experimental system that showed efficacy in
      an enteric infection model. Thus, in combination with exhaustive bacterial strain
      collections and systems-based approaches, genome-guided design can be used to
      generate insights into microbe-microbe and microbe-host interactions for the
      investigation of ecological and disease-relevant mechanisms in the intestine.

PMID- 27869791
TI  - Corrigendum: Endogenous Arabidopsis messenger RNAs transported to distant
      tissues.

PMID- 27869790
TI  - The genome of Onchocerca volvulus, agent of river blindness.
AB  - Human onchocerciasis is a serious neglected tropical disease caused by the
      filarial nematode Onchocerca volvulus that can lead to blindness and chronic
      disability. Control of the disease relies largely on mass administration of a
      single drug, and the development of new drugs and vaccines depends on a better
      knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus
      and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly
      for any parasitic nematode to date, giving a glimpse into the evolution of
      filarial parasite chromosomes and proteomes. This resource was used to
      investigate gene families with key functions that could be potentially exploited
      as targets for future drugs. Using metabolic reconstruction of the nematode and
      its endosymbiont, we identified enzymes that are likely to be essential for O.
      volvulus viability. In addition, we have generated a list of proteins that could
      be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing
      starting points for anti-onchocerciasis drug development.

PMID- 27869792
TI  - Genomic diversity in Onchocerca volvulus and its Wolbachia endosymbiont.
AB  - Ongoing elimination efforts have altered the global distribution of Onchocerca
      volvulus, the agent of river blindness, and further population restructuring is
      expected as efforts continue. Therefore, a better understanding of population
      genetic processes and their effect on biogeography is needed to support
      elimination goals. We describe O. volvulus genome variation in 27 isolates from
      the early 1990s (before widespread mass treatment) from four distinct locales:
      Ecuador, Uganda, the West African forest and the West African savanna. We
      observed genetic substructuring between Ecuador and West Africa and between the
      West African forest and savanna bioclimes, with evidence of unidirectional gene
      flow from savanna to forest strains. We identified forest:savanna-discriminatory
      genomic regions and report a set of ancestry informative loci that can be used to
      differentiate between forest, savanna and admixed isolates, which has not
      previously been possible. We observed mito-nuclear discordance possibly stemming
      from incomplete lineage sorting. The catalogue of the nuclear, mitochondrial and
      endosymbiont DNA variants generated in this study will support future basic and
      translational onchocerciasis research, with particular relevance for ongoing
      control programmes, and boost efforts to characterize drug, vaccine and
      diagnostic targets.

PMID- 27869793
TI  - Lyme disease spirochaete Borrelia burgdorferi does not require thiamin.
AB  - Thiamin pyrophosphate (ThDP), the active form of thiamin (vitamin B1), is
      believed to be an essential cofactor for all living organisms1,2. Here, we report
      the unprecedented result that thiamin is dispensable for the growth of the Lyme
      disease pathogen Borrelia burgdorferi (Bb)3. Bb lacks genes for thiamin
      biosynthesis and transport as well as known ThDP-dependent enzymes4, and we were
      unable to detect thiamin or its derivatives in Bb cells. We showed that
      eliminating thiamin in vitro and in vivo using BcmE, an enzyme that degrades
      thiamin, has no impact on Bb growth and survival during its enzootic infectious
      cycle. Finally, high-performance liquid chromatography analysis reveals that the
      level of thiamin and its derivatives in Ixodes scapularis ticks, the enzootic
      vector of Bb, is extremely low. These results suggest that by dispensing with use
      of thiamin, Borrelia, and perhaps other tick-transmitted bacterial pathogens, are
      uniquely adapted to survive in tick vectors before transmitting to mammalian
      hosts. To our knowledge, such a mechanism has not been reported previously in any
      living organisms.

PMID- 27869794
TI  - Covalently deposited dyes: a new chromogen paradigm that facilitates analysis of
      multiple biomarkers in situ.
AB  - Multiplexed analysis of multiple biomarkers in a tissue sample requires use of
      reporter dyes with specific spectral properties that enable discrimination of
      signals. Conventional chromogens with broad absorbance spectra, widely used in
      immunohistochemistry (IHC), offer limited utility for multiplexed detection. Many
      dyes with narrow absorbance spectra, eg rhodamines, fluoresceins, and cyanines,
      potentially useful for multiplexed detection are well-characterized; however,
      generation of a chromogenic reagent useful for IHC analysis has not been
      demonstrated. Studies reported herein demonstrate utility of tyramine-chemistry
      for synthesis of a wide variety of new chromogenic dye conjugates useful for
      multiplexed in situ analysis using conventional light microscopes. The dyes,
      useful individually or in blends to generate new colors, provide signal
      sensitivity and dynamic range similar to conventional DAB chromogen, while
      enabling analysis of co-localized biomarkers. It is anticipated that this new
      paradigm will enable generation of a wide variety of new chromogens, useful for
      both research and clinical biomarker analysis that will benefit clinicians and
      patients.

PMID- 27869795
TI  - CD68/macrosialin: not just a histochemical marker.
AB  - CD68 is a heavily glycosylated glycoprotein that is highly expressed in
      macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as
      a valuable cytochemical marker to immunostain monocyte/macrophages in the
      histochemical analysis of inflamed tissues, tumor tissues, and other
      immunohistopathological applications. CD68 alone or in combination with other
      cell markers of tumor-associated macrophages showed a good predictive value as a
      prognostic marker of survival in cancer patients. Lowression of CD68 was found in
      the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells,
      etc), and tumor cells. Cell-specific CD68 expression and differentiated
      expression levels are determined by the complex interplay between transcription
      factors, regulatory transcriptional elements, and epigenetic factors. Human CD68
      and its mouse ortholog macrosialin belong to the family of LAMP proteins located
      in the lysosomal membrane and share many structural similarities such as the
      presence of the LAMP-like domain. Except for a second LAMP-like domain present in
      LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in
      ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic
      cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is
      mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to
      the cell surface. However, the role of CD68 as a scavenger receptor remains to be
      confirmed. It seems that CD68 is not involved in binding bacterial/viral
      pathogens, innate, inflammatory or humoral immune responses, although it may
      potentially be involved in antigen processing/presentation. CD68 could be
      functionally important in osteoclasts since its deletion leads to reduced bone
      resorption capacity. The role of CD68 in atherosclerosis is contradictory.

PMID- 27869796
TI  - Longitudinal microcomputed tomography-derived biomarkers for lung metastasis
      detection in a syngeneic mouse model: added value to bioluminescence imaging.
AB  - With more patients dying from metastasis than from primary cancers, metastasis is
      a very important area in cancer research. Investigators thereby heavily rely on
      animal models of metastasis to common organs such as the lung to improve our
      insight into the pathogenesis and to research novel therapeutic approaches to
      combat metastasis. In this experimental context, novel tools that allow
      longitudinal monitoring of lung metastasis in individual animals are highly
      needed. We have therefore evaluated for the first time microcomputed tomography
      (MUCT) as a very efficient and crossvalidated means to noninvasively and
      repeatedly monitor metastasis to the lung in individual, free-breathing syngeneic
      mice. Two individual clones of KLN205 cancer cells were intravenously injected in
      syngeneic DBA/2 mice and lung metastasis was monitored weekly during 3 weeks
      using MUCT, and was compared with the current gold standard histology and
      bioluminescence imaging (BLI). MUCT enabled us to visualize diffuse tumor
      morphology and also to extract four different biomarkers that quantify not only
      tumor load but also aerated space in the lung as a marker of vital lung capacity
      and potential compensatory mechanisms. Complementary to BLI, applying this novel
      MUCT-based approach enabled us to unravel sensitively and efficiently differences
      in metastatic potential between two cellular clones. In conclusion, MUCT and BLI
      offer biomarkers that describe different and complementary aspects of lung
      metastasis, underlining the importance of multimodality follow-up. The added
      value of MUCT findings is important to better assess lung metastasis and
      host/lung response in preclinical studies, which will be valuable for
      translational applications.

PMID- 27869797
TI  - The receptor for advanced glycation end products impairs collateral formation in
      both diabetic and non-diabetic mice.
AB  - Diabetics often have poor perfusion in their limbs as a result of peripheral
      artery disease and an impaired ability to generate collateral vessels. The
      receptor for advanced glycation end products (RAGE) is one protein that is
      thought to play a detrimental role in collateral development in diabetics due to
      increased levels of advanced glycation end products (AGE), one of its ligands, in
      diabetes. Thus, the aim of this study was to investigate the role of RAGE in both
      diabetic and non-diabetic settings in a model of collateral formation in mice.
      Streptozotocin was used to induce diabetes in both wild type and RAGE knockout
      mice. Increased levels of the AGE, NE-(carboxymethyl) lysine (CML), were
      confirmed via an ELISA. A hindlimb ischemia model, in which the femoral artery is
      ligated, was used to drive collateral growth and reperfusion was assessed using
      laser Doppler perfusion imaging and histological analysis of vessels in the
      muscle. Both of these measurements showed impaired collateral growth in diabetic
      compared with wild-type mice as well as improved collateral growth in both
      diabetic and non-diabetic RAGE knockout mice when compared their wild-type
      counterparts. Distance on a freely accessed running wheel, used as a measure of
      perfusion recovery, showed that wild-type diabetic mice had functionally impaired
      recovery compared with their wild-type counterparts. Immunohistochemistry and
      immunoblotting showed that HMGB-1 (high-mobility group box 1), another RAGE
      ligand, was increased in the ischemic leg compared with the non-ischemic leg in
      all mice. This increase in HMGB-1 may explain improvement in animals lacking RAGE
      and its subsequent signaling. In conclusion, this study shows that RAGE impairs
      collateral growth in a diabetic setting and also in a non-diabetic setting. This
      demonstrates the importance of RAGE and alternate RAGE ligands in the setting of
      collateral vessel growth.

PMID- 27869798
TI  - Gluten-induced symptoms in diarrhea-predominant irritable bowel syndrome are
      associated with increased myosin light chain kinase activity and claudin-15
      expression.
AB  - The mechanisms underlying diarrhea-predominant irritable bowel syndrome (IBS-D)
      are poorly understood, but increased intestinal permeability is thought to
      contribute to symptoms. A recent clinical trial of gluten-free diet (GFD)
      demonstrated symptomatic improvement, relative to gluten-containing diet (GCD),
      which was associated with reduced intestinal permeability in non-celiac disease
      IBS-D patients. The aim of this study was to characterize intestinal epithelial
      tight junction composition in IBS-D before and after dietary gluten challenge.
      Biopsies from 27 IBS-D patients (13 GFD and 14 GCD) were examined by H&E staining
      and semiquantitative immunohistochemistry for phosphorylated myosin II regulatory
      light chain (MLC), MLC kinase, claudin-2, claudin-8 and claudin-15. Diet-induced
      changes were assessed and correlated with urinary mannitol excretion (after oral
      administration). In the small intestine, epithelial MLC phosphorylation was
      increased or decreased by GCD or GFD, respectively, and this correlated with
      increased intestinal permeability (P<0.03). Colonocyte expression of the
      paracellular Na+ channel claudin-15 was also markedly augmented following GCD
      challenge (P<0.05). Conversely, colonic claudin-2 expression correlated with
      reduced intestinal permeability (P<0.03). Claudin-8 expression was not affected
      by dietary challenge. These data show that alterations in MLC phosphorylation and
      claudin-15 and claudin-2 expression are associated with gluten-induced
      symptomatology and intestinal permeability changes in IBS-D. The results provide
      new insight into IBS-D mechanisms and can explain permeability responses to
      gluten challenge in these patients.

PMID- 27869799
TI  - Transcript, protein and metabolite temporal dynamics in the CAM plant Agave.
AB  - Already a proven mechanism for drought resilience, crassulacean acid metabolism
      (CAM) is a specialized type of photosynthesis that maximizes water-use efficiency
      by means of an inverse (compared to C3 and C4 photosynthesis) day/night pattern
      of stomatal closure/opening to shift CO2 uptake to the night, when
      evapotranspiration rates are low. A systems-level understanding of temporal
      molecular and metabolic controls is needed to define the cellular behaviour
      underpinning CAM. Here, we report high-resolution temporal behaviours of
      transcript, protein and metabolite abundances across a CAM diel cycle and, where
      applicable, compare the observations to the well-established C3 model plant
      Arabidopsis. A mechanistic finding that emerged is that CAM operates with a diel
      redox poise that is shifted relative to that in Arabidopsis. Moreover, we
      identify widespread rescheduled expression of genes associated with signal
      transduction mechanisms that regulate stomatal opening/closing. Controlled
      production and degradation of transcripts and proteins represents a timing
      mechanism by which to regulate cellular function, yet knowledge of how this
      molecular timekeeping regulates CAM is unknown. Here, we provide new insights
      into complex post-transcriptional and -translational hierarchies that govern CAM
      in Agave. These data sets provide a resource to inform efforts to engineer more
      efficient CAM traits into economically valuable C3 crops.

PMID- 27869801
TI  - Direct dorsal hippocampal-prelimbic cortex connections strengthen fear memories.
AB  - The ability to regulate the consolidation and strengthening of memories for
      threatening experiences is critical for mental health, and its dysregulation may
      lead to psychopathologies. Re-exposure to the context in which the threat was
      experienced can either increase or decrease fear response through distinct
      processes known, respectively, as reconsolidation or extinction. Using a context
      retrieval-dependent memory-enhancement model in rats, we report that memory
      strengthens through activation of direct projections from dorsal hippocampus to
      prelimbic (PL) cortex and activation of critical PL molecular mechanisms that are
      not required for extinction. Furthermore, while sustained PL brain-derived
      neurotrophic factor (BDNF) expression is required for memory consolidation,
      retrieval engages PL BDNF to regulate excitatory and inhibitory synaptic proteins
      neuroligin 1 and neuroligin 2, which promote memory strengthening while
      inhibiting extinction. Thus, context retrieval-mediated fear-memory enhancement
      results from a concerted action of mechanisms that strengthen memory through
      reconsolidation while suppressing extinction.

PMID- 27869800
TI  - A rapidly acting glutamatergic ARC->PVH satiety circuit postsynaptically
      regulated by alpha-MSH.
AB  - Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger.
      Agouti-related protein (AgRP) neurons in the ARC (ARCAgRP neurons) are stimulated
      by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro
      opiomelanocortin (ARCPOMC) neurons are viewed as the counterpoint to ARCAgRP
      neurons. They are regulated in an opposite fashion and decrease hunger. However,
      unlike ARCAgRP neurons, ARCPOMC neurons are extremely slow in affecting hunger
      (many hours). Thus, a temporally analogous, rapid ARC satiety pathway does not
      exist or is presently unidentified. Here we show that glutamate-releasing ARC
      neurons expressing oxytocin receptor, unlike ARCPOMC neurons, rapidly cause
      satiety when chemo- or optogenetically manipulated. These glutamatergic ARC
      projections synaptically converge with GABAergic ARCAgRP projections on
      melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular
      hypothalamus (PVHMC4R neurons). Transmission across the ARCGlutamatergic->PVHMC4R
      synapse is potentiated by the ARCPOMC neuron-derived MC4R agonist, alpha
      melanocyte stimulating hormone (alpha-MSH). This excitatory ARC->PVH satiety
      circuit, and its modulation by alpha-MSH, provides insight into regulation of
      hunger and satiety.

PMID- 27869802
TI  - Molecular analysis of circulating tumor cells identifies distinct copy-number
      profiles in patients with chemosensitive and chemorefractory small-cell lung
      cancer.
AB  - In most patients with small-cell lung cancer (SCLC)-a metastatic, aggressive
      disease-the condition is initially chemosensitive but then relapses with acquired
      chemoresistance. In a minority of patients, however, relapse occurs within 3
      months of initial treatment; in these cases, disease is defined as
      chemorefractory. The molecular mechanisms that differentiate chemosensitive from
      chemorefractory disease are currently unknown. To identify genetic features that
      distinguish chemosensitive from chemorefractory disease, we examined copy-number
      aberrations (CNAs) in circulating tumor cells (CTCs) from pretreatment SCLC blood
      samples. After analysis of 88 CTCs isolated from 13 patients (training set), we
      generated a CNA-based classifier that we validated in 18 additional patients
      (testing set, 112 CTC samples) and in six SCLC patient-derived CTC explant
      tumors. The classifier correctly assigned 83.3% of the cases as chemorefractory
      or chemosensitive. Furthermore, a significant difference was observed in
      progression-free survival (PFS) (Kaplan-Meier P value = 0.0166) between patients
      designated as chemorefractory or chemosensitive by using the baseline CNA
      classifier. Notably, CTC CNA profiles obtained at relapse from five patients with
      initially chemosensitive disease did not switch to a chemorefractory CNA profile,
      which suggests that the genetic basis for initial chemoresistance differs from
      that underlying acquired chemoresistance.

PMID- 27869803
TI  - Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable
      vulnerability of RNF43-mutant pancreatic tumors.
AB  - Forward genetic screens with CRISPR-Cas9 genome editing enable high-resolution
      detection of genetic vulnerabilities in cancer cells. We conducted genome-wide
      CRISPR-Cas9 screens in RNF43-mutant pancreatic ductal adenocarcinoma (PDAC)
      cells, which rely on Wnt signaling for proliferation. Through these screens, we
      discovered a unique requirement for a Wnt signaling circuit: engaging FZD5, one
      of the ten Frizzled receptors encoded in the human genome. Our results uncover an
      underappreciated level of context-dependent specificity at the Wnt receptor
      level. We further derived a panel of recombinant antibodies that reports the
      expression of nine FZD proteins and confirms that FZD5 functional specificity
      cannot be explained by protein expression patterns. Additionally, antibodies that
      specifically bind FZD5 and FZD8 robustly inhibited the growth of RNF43-mutant
      PDAC cells grown in vitro and as xenografts in vivo, providing orthogonal support
      for the functional specificity observed genetically. Proliferation of a patient
      derived PDAC cell line harboring an RNF43 variant was also selectively inhibited
      by the FZD5 antibodies, further demonstrating their use as a potential targeted
      therapy. Tumor organoid cultures from colorectal carcinoma patients that carried
      RNF43 mutations were also sensitive to the FZD5 antibodies, highlighting the
      potential generalizability of these findings beyond PDAC. Our results show that
      CRIPSR-based genetic screens can be leveraged to identify and validate cell
      surface targets for antibody development and therapy.

PMID- 27869804
TI  - Systemic depletion of L-cyst(e)ine with cyst(e)inase increases reactive oxygen
      species and suppresses tumor growth.
AB  - Cancer cells experience higher oxidative stress from reactive oxygen species
      (ROS) than do non-malignant cells because of genetic alterations and abnormal
      growth; as a result, maintenance of the antioxidant glutathione (GSH) is
      essential for their survival and proliferation. Under conditions of elevated ROS,
      endogenous L-cysteine (L-Cys) production is insufficient for GSH synthesis. This
      necessitates uptake of L-Cys that is predominantly in its disulfide form, L
      cystine (CSSC), via the xCT(-) transporter. We show that administration of an
      engineered and pharmacologically optimized human cyst(e)inase enzyme mediates
      sustained depletion of the extracellular L-Cys and CSSC pool in mice and non
      human primates. Treatment with this enzyme selectively causes cell cycle arrest
      and death in cancer cells due to depletion of intracellular GSH and ensuing
      elevated ROS; yet this treatment results in no apparent toxicities in mice even
      after months of continuous treatment. Cyst(e)inase suppressed the growth of
      prostate carcinoma allografts, reduced tumor growth in both prostate and breast
      cancer xenografts and doubled the median survival time of TCL1-Tg:p53-/- mice,
      which develop disease resembling human chronic lymphocytic leukemia. It was
      observed that enzyme-mediated depletion of the serum L-Cys and CSSC pool
      suppresses the growth of multiple tumors, yet is very well tolerated for
      prolonged periods, suggesting that cyst(e)inase represents a safe and effective
      therapeutic modality for inactivating antioxidant cellular responses in a wide
      range of malignancies.

PMID- 27869807
TI  - A proposed biology- and biomarker-based algorithm for management of acute GvHD.

PMID- 27869806
TI  - Preliminary efficacy of a brief family intervention to prevent declining quality
      of life secondary to parental bone marrow transplantation.
AB  - The primary purpose of this research was to develop and evaluate the efficacy and
      feasibility of a brief, cost-effective family-focused intervention to promote
      adaptive coping and quality of life throughout a parent's bone marrow
      transplantation (BMT). Targeted outcomes were cohesion, decreased use of
      avoidance coping, open communication and effective management of emotional
      distress. Participants included an intervention group of 31 families and 29
      families in a control group who received usual care. Each family included the BMT
      recipient, a partner/caregiver and children 10-18 years old. The intervention
      included two dyadic sessions for the BMT recipient and the partner/caregiver, one
      individual session for the caregiver and two digital video discs (DVDs) for
      children. Statistical analyses indicated that the intervention had a positive
      impact on at least one aspect of the adaptation of each family member. Caregivers
      reported the most distress but benefitted least from the intervention, whereas
      recipients and children reported improvement in distress. Ratings of
      satisfaction/acceptability were high, with 97% responding that they would
      recommend the intervention to others. Plans for future research include increased
      intervention intensity for the caregiver, a larger more diverse sample and
      implementation over an extended period post BMT.

PMID- 27869805
TI  - Engineered human pluripotent-stem-cell-derived intestinal tissues with a
      functional enteric nervous system.
AB  - The enteric nervous system (ENS) of the gastrointestinal tract controls many
      diverse functions, including motility and epithelial permeability. Perturbations
      in ENS development or function are common, yet there is no human model for
      studying ENS-intestinal biology and disease. We used a tissue-engineering
      approach with embryonic and induced pluripotent stem cells (PSCs) to generate
      human intestinal tissue containing a functional ENS. We recapitulated normal
      intestinal ENS development by combining human-PSC-derived neural crest cells
      (NCCs) and developing human intestinal organoids (HIOs). NCCs recombined with
      HIOs in vitro migrated into the mesenchyme, differentiated into neurons and glial
      cells and showed neuronal activity, as measured by rhythmic waves of calcium
      transients. ENS-containing HIOs grown in vivo formed neuroglial structures
      similar to a myenteric and submucosal plexus, had functional interstitial cells
      of Cajal and had an electromechanical coupling that regulated waves of
      propagating contraction. Finally, we used this system to investigate the cellular
      and molecular basis for Hirschsprung's disease caused by a mutation in the gene
      PHOX2B. This is, to the best of our knowledge, the first demonstration of human
      PSC-derived intestinal tissue with a functional ENS and how this system can be
      used to study motility disorders of the human gastrointestinal tract.

PMID- 27869809
TI  - Absence of spontaneous response improvement beyond day +100 after autologous stem
      cell transplantation in multiple myeloma.
AB  - The response evaluation after autologous stem-cell transplantation (ASCT) is
      usually performed at day +100 in patients with multiple myeloma (MM). A recent
      report suggests that improvement in the response can be observed beyond day +100.
      The aim of the present study has been to evaluate the rate of improved response
      and outcome beyond day +100 after ASCT, with and without maintenance therapy. One
      hundred and forty-four patients who underwent single ASCT with chemosensitive
      disease and achieved less than CR at day 100 post ASCT were evaluated. Seventy
      four patients (51.4%) did not receive any maintenance with only one of them
      showing an upgrade in the response. The remaining 70 patients (48.6%) received
      maintenance therapy; eleven of them (15.7%) improved their response beyond day
      +100. The outcome of these patients was better than those who did not upgrade
      their response in both progression-free survival and overall survival (P=0.019
      and P=0.031, respectively). In conclusion, the improvement in response beyond day
      +100 after ASCT in patients not receiving any therapy is exceedingly rare. A
      minority of patients receiving maintenance therapy after ASCT upgrades their
      response and this finding is associated with better outcome.

PMID- 27869810
TI  - Hematopoietic stem cell transplantation in FANCJ/BRIP1 fanconi anemia.

PMID- 27869808
TI  - Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD:
      an analysis of the JSHCT.
AB  - A nationwide retrospective study for the clinical outcomes of 99 patients who had
      received thymoglobulin at a median total dose of 2.5 mg/kg (range, 0.5-18.5
      mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted.
      Of the 92 evaluable patients, improvement (complete or partial response) was
      observed in 55 patients (60%). Multivariate analysis demonstrated that male sex
      and grade III and IV acute GvHD were associated with a lower improvement rate,
      whereas thymoglobulin dose (<2.0, 2.0-3.9 and ?4.0 mg/kg) was NS. Factors
      associated with significantly higher nonrelapse mortality included higher patient
      age (?50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of
      thymoglobulin (hazard ratio, 2.55; 95% confidence interval, 1.34-4.85; P=0.004
      for 2.0-3.9 mg/kg group and 1.79; 0.91-3.55; P=0.093 for ?4.0 mg/kg group).
      Higher dose of thymoglobulin was associated with a higher incidence of bacterial
      infections, CMV antigenemia and any additional infection. Taken together, low
      dose thymoglobulin at a median total dose of 2.5 mg/kg provides a comparable
      response rate to standard-dose thymoglobulin reported previously, and <2.0 mg/kg
      thymoglobulin is recommended in terms of the balance between efficacy and adverse
      effects.

PMID- 27869811
TI  - Diffuse large B-cell lymphoma: the challenge of relapse after an autologous stem
      cell transplant.

PMID- 27869812
TI  - Low day +100 serum epidermal growth factor levels are associated with acute GvHD
      after allogeneic hematopoietic cell transplantation.

PMID- 27869813
TI  - Covalently circularized nanodiscs for studying membrane proteins and viral entry.
AB  - We engineered covalently circularized nanodiscs (cNDs) which, compared with
      standard nanodiscs, exhibit enhanced stability, defined diameter sizes and
      tunable shapes. Reconstitution into cNDs enhanced the quality of nuclear magnetic
      resonance spectra for both VDAC-1, a beta-barrel membrane protein, and the G
      protein-coupled receptor NTR1, an alpha-helical membrane protein. In addition, we
      used cNDs to visualize how simple, nonenveloped viruses translocate their genomes
      across membranes to initiate infection.

PMID- 27869814
TI  - Photometry unlocks 3D information from 2D localization microscopy data.
AB  - We developed a straightforward photometric method, temporal, radial-aperture
      based intensity estimation (TRABI), that allows users to extract 3D information
      from existing 2D localization microscopy data. TRABI uses the accurate
      determination of photon numbers in different regions of the emission pattern of
      single emitters to generate a z-dependent photometric parameter. This method can
      determine fluorophore positions up to 600 nm from the focal plane and can be
      combined with biplane detection to further improve axial localization.

PMID- 27869815
TI  - TACO produces robust multisample transcriptome assemblies from RNA-seq.
AB  - Accurate transcript structure and abundance inference from RNA sequencing (RNA
      seq) data is foundational for molecular discovery. Here we present TACO, a
      computational method to reconstruct a consensus transcriptome from multiple RNA
      seq data sets. TACO employs novel change-point detection to demarcate transcript
      start and end sites, leading to improved reconstruction accuracy compared with
      other tools in its class. The tool is available at http://tacorna.github.io and
      can be readily incorporated into RNA-seq analysis workflows.

PMID- 27869816
TI  - mScarlet: a bright monomeric red fluorescent protein for cellular imaging.
AB  - We report the engineering of mScarlet, a truly monomeric red fluorescent protein
      with record brightness, quantum yield (70%) and fluorescence lifetime (3.9 ns).
      We developed mScarlet starting with a consensus synthetic template and using
      improved spectroscopic screening techniques; mScarlet's crystal structure reveals
      a planar and rigidified chromophore. mScarlet outperforms existing red
      fluorescent proteins as a fusion tag, and it is especially useful as a Forster
      resonance energy transfer (FRET) acceptor in ratiometric imaging.

PMID- 27869817
TI  - The aryl hydrocarbon receptor AhR links atopic dermatitis and air pollution via
      induction of the neurotrophic factor artemin.
AB  - Atopic dermatitis is increasing worldwide in correlation with air pollution.
      Various organic components of pollutants activate the transcription factor AhR
      (aryl hydrocarbon receptor). Through the use of AhR-CA mice, whose keratinocytes
      express constitutively active AhR and that develop atopic-dermatitis-like
      phenotypes, we identified Artn as a keratinocyte-specific AhR target gene whose
      product (the neurotrophic factor artemin) was responsible for epidermal hyper
      innervation that led to hypersensitivity to pruritus. The activation of AhR via
      air pollutants induced expression of artemin, alloknesis, epidermal hyper
      innervation and inflammation. AhR activation and ARTN expression were positively
      correlated in the epidermis of patients with atopic dermatitis. Thus, AhR in
      keratinocytes senses environmental stimuli and elicits an atopic-dermatitis
      pathology. We propose a mechanism of air-pollution-induced atopic dermatitis via
      activation of AhR.

PMID- 27869818
TI  - TCRalpha-TCRbeta pairing controls recognition of CD1d and directs the development
      of adipose NKT cells.
AB  - The interaction between the T cell antigen receptor (TCR) expressed by natural
      killer T cells (NKT cells) and the antigen-presenting molecule CD1d is distinct
      from interactions between the TCR and major histocompatibility complex (MHC). Our
      molecular modeling suggested that a hydrophobic patch created after TCRalpha
      TCRbeta pairing has a role in maintaining the conformation of the NKT cell TCR.
      Disruption of this patch ablated recognition of CD1d by the NKT cell TCR but not
      interactions of the TCR with MHC. Partial disruption of the patch, while
      permissive to the recognition of CD1d, significantly altered NKT cell
      development, which resulted in the selective accumulation of adipose-tissue
      resident NKT cells. These results indicate that a key component of the TCR is
      essential for the development of a distinct population of NKT cells.

PMID- 27869819
TI  - A cycle of Zap70 kinase activation and release from the TCR amplifies and
      disperses antigenic stimuli.
AB  - Cell-surface-receptor pathways amplify weak, rare and local stimuli to induce
      cellular responses. This task is accomplished despite signaling components that
      segregate into nanometer-scale membrane domains. Here we describe a 'catch-and
      release' mechanism that amplified and dispersed stimuli by releasing activated
      kinases from receptors lacking intrinsic catalytic activity. Specifically, we
      discovered a cycle of recruitment, activation and release for Zap70 kinases at
      phosphorylated T cell antigen receptors (TCRs). This turned the TCR into a
      'catalytic unit' that amplified antigenic stimuli. Zap70 released from the TCR
      remained at the membrane, translocated, and phosphorylated spatially distinct
      substrates. The mechanisms described here are based on widely used protein
      domains and post-translational modifications; therefore, many membrane-associated
      pathways might employ similar mechanisms for signal amplification and dispersion.

PMID- 27869822
TI  - Current-induced switching in a magnetic insulator.
AB  - The spin Hall effect in heavy metals converts charge current into pure spin
      current, which can be injected into an adjacent ferromagnet to exert a torque.
      This spin-orbit torque (SOT) has been widely used to manipulate the magnetization
      in metallic ferromagnets. In the case of magnetic insulators (MIs), although
      charge currents cannot flow, spin currents can propagate, but current-induced
      control of the magnetization in a MI has so far remained elusive. Here we
      demonstrate spin-current-induced switching of a perpendicularly magnetized
      thulium iron garnet film driven by charge current in a Pt overlayer. We estimate
      a relatively large spin-mixing conductance and damping-like SOT through spin Hall
      magnetoresistance and harmonic Hall measurements, respectively, indicating
      considerable spin transparency at the Pt/MI interface. We show that spin currents
      injected across this interface lead to deterministic magnetization reversal at
      low current densities, paving the road towards ultralow-dissipation spintronic
      devices based on MIs.

PMID- 27869820
TI  - TET proteins regulate the lineage specification and TCR-mediated expansion of
      iNKT cells.
AB  - TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other
      oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse
      CD4+CD8+ double-positive thymocytes resulted in dysregulated development and
      proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double
      knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage,
      with increased DNA methylation and impaired expression of genes encoding the key
      lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO
      iNKT cells into immunocompetent recipient mice resulted in an uncontrolled
      expansion that was dependent on the nonclassical major histocompatibility complex
      (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data
      indicate that TET proteins regulate iNKT cell fate by ensuring their proper
      development and maturation and by suppressing aberrant proliferation mediated by
      the T cell antigen receptor (TCR).

PMID- 27869821
TI  - Synthetic recording and in situ readout of lineage information in single cells.
AB  - Reconstructing the lineage relationships and dynamic event histories of
      individual cells within their native spatial context is a long-standing challenge
      in biology. Many biological processes of interest occur in optically opaque or
      physically inaccessible contexts, necessitating approaches other than direct
      imaging. Here we describe a synthetic system that enables cells to record lineage
      information and event histories in the genome in a format that can be
      subsequently read out of single cells in situ. This system, termed memory by
      engineered mutagenesis with optical in situ readout (MEMOIR), is based on a set
      of barcoded recording elements termed scratchpads. The state of a given
      scratchpad can be irreversibly altered by CRISPR/Cas9-based targeted mutagenesis,
      and later read out in single cells through multiplexed single-molecule RNA
      fluorescence hybridization (smFISH). Using MEMOIR as a proof of principle, we
      engineered mouse embryonic stem cells to contain multiple scratchpads and other
      recording components. In these cells, scratchpads were altered in a progressive
      and stochastic fashion as the cells proliferated. Analysis of the final states of
      scratchpads in single cells in situ enabled reconstruction of lineage information
      from cell colonies. Combining analysis of endogenous gene expression with lineage
      reconstruction in the same cells further allowed inference of the dynamic rates
      at which embryonic stem cells switch between two gene expression states. Finally,
      using simulations, we show how parallel MEMOIR systems operating in the same cell
      could enable recording and readout of dynamic cellular event histories. MEMOIR
      thus provides a versatile platform for information recording and in situ, single
      cell readout across diverse biological systems.

PMID- 27869823
TI  - High-resolution three-dimensional structural microscopy by single-angle Bragg
      ptychography.
AB  - Coherent X-ray microscopy by phase retrieval of Bragg diffraction intensities
      enables lattice distortions within a crystal to be imaged at nanometre-scale
      spatial resolutions in three dimensions. While this capability can be used to
      resolve structure-property relationships at the nanoscale under working
      conditions, strict data measurement requirements can limit the application of
      current approaches. Here, we introduce an efficient method of imaging three
      dimensional (3D) nanoscale lattice behaviour and strain fields in crystalline
      materials with a methodology that we call 3D Bragg projection ptychography
      (3DBPP). This method enables 3D image reconstruction of a crystal volume from a
      series of two-dimensional X-ray Bragg coherent intensity diffraction patterns
      measured at a single incident beam angle. Structural information about the sample
      is encoded along two reciprocal-space directions normal to the Bragg diffracted
      exit beam, and along the third dimension in real space by the scanning beam. We
      present our approach with an analytical derivation, a numerical demonstration,
      and an experimental reconstruction of lattice distortions in a component of a
      nanoelectronic prototype device.

PMID- 27869824
TI  - Reducing the efficiency-stability-cost gap of organic photovoltaics with highly
      efficient and stable small molecule acceptor ternary solar cells.
AB  - Technological deployment of organic photovoltaic modules requires improvements in
      device light-conversion efficiency and stability while keeping material costs
      low. Here we demonstrate highly efficient and stable solar cells using a ternary
      approach, wherein two non-fullerene acceptors are combined with both a scalable
      and affordable donor polymer, poly(3-hexylthiophene) (P3HT), and a high
      efficiency, low-bandgap polymer in a single-layer bulk-heterojunction device. The
      addition of a strongly absorbing small molecule acceptor into a P3HT-based non
      fullerene blend increases the device efficiency up to 7.7 +/- 0.1% without any
      solvent additives. The improvement is assigned to changes in microstructure that
      reduce charge recombination and increase the photovoltage, and to improved light
      harvesting across the visible region. The stability of P3HT-based devices in
      ambient conditions is also significantly improved relative to polymer:fullerene
      devices. Combined with a low-bandgap donor polymer (PBDTTT-EFT, also known as
      PCE10), the two mixed acceptors also lead to solar cells with 11.0 +/- 0.4%
      efficiency and a high open-circuit voltage of 1.03 +/- 0.01 V.

PMID- 27869825
TI  - Entropic contributions enhance polarity compensation for CeO2(100) surfaces.
AB  - Surface structure controls the physical and chemical response of materials.
      Surface polar terminations are appealing because of their unusual properties but
      they are intrinsically unstable. Several mechanisms, namely metallization,
      adsorption, and ordered reconstructions, can remove thermodynamic penalties
      rendering polar surfaces partially stable. Here, for CeO2(100), we report a
      complementary stabilization mechanism based on surface disorder that has been
      unravelled through theoretical simulations that: account for surface energies and
      configurational entropies; show the importance of the ion distribution
      degeneracy; and identify low diffusion barriers between conformations that ensure
      equilibration. Disordered configurations in oxides might also be further
      stabilized by preferential adsorption of water. The entropic stabilization term
      will appear for surfaces with a high number of empty sites, typically achieved
      when removing part of the ions in a polar termination to make the layer charge
      zero. Assessing the impact of surface disorder when establishing new structure
      activity relationships remains a challenge.

PMID- 27869826
TI  - Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2
      in enhancer hijacking.
AB  - Extensive prior research focused on somatic copy-number alterations (SCNAs)
      affecting cancer genes, yet the extent to which recurrent SCNAs exert their
      influence through rearrangement of cis-regulatory elements (CREs) remains
      unclear. Here we present a framework for inferring cancer-related gene
      overexpression resulting from CRE reorganization (e.g., enhancer hijacking) by
      integrating SCNAs, gene expression data and information on topologically
      associating domains (TADs). Analysis of 7,416 cancer genomes uncovered several
      pan-cancer candidate genes, including IRS4, SMARCA1 and TERT. We demonstrate that
      IRS4 overexpression in lung cancer is associated with recurrent deletions in cis,
      and we present evidence supporting a tumor-promoting role. We additionally
      pursued cancer-type-specific analyses and uncovered IGF2 as a target for enhancer
      hijacking in colorectal cancer. Recurrent tandem duplications intersecting with a
      TAD boundary mediate de novo formation of a 3D contact domain comprising IGF2 and
      a lineage-specific super-enhancer, resulting in high-level gene activation. Our
      framework enables systematic inference of CRE rearrangements mediating
      dysregulation in cancer.

PMID- 27869827
TI  - Titin-truncating variants affect heart function in disease cohorts and the
      general population.
AB  - Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM).
      TTNtv are also encountered in ~1% of the general population, where they may be
      silent, perhaps reflecting allelic factors. To better understand TTNtv, we
      integrated TTN allelic series, cardiac imaging and genomic data in humans and
      studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout
      titin were significantly associated with DCM. Ribosomal profiling in rat showed
      the translational footprint of premature stop codons in Ttn, TTNtv-position
      independent nonsense-mediated degradation of the mutant allele and a signature of
      perturbed cardiac metabolism. Heart physiology in rats with TTNtv was
      unremarkable at baseline but became impaired during cardiac stress. In healthy
      humans, machine-learning-based analysis of high-resolution cardiac imaging showed
      TTNtv to be associated with eccentric cardiac remodeling. These data show that
      TTNtv have molecular and physiological effects on the heart across species, with
      a continuum of expressivity in health and disease.

PMID- 27869828
TI  - Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex
      bias.
AB  - There is a striking and unexplained male predominance across many cancer types. A
      subset of X-chromosome genes can escape X-inactivation, which would protect
      females from complete functional loss by a single mutation. To identify putative
      'escape from X-inactivation tumor-suppressor' (EXITS) genes, we examined somatic
      alterations from >4,100 cancers across 21 tumor types for sex bias. Six of 783
      non-pseudoautosomal region (PAR) X-chromosome genes (ATRX, CNKSR2, DDX3X, KDM5C,
      KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males
      (based on a false discovery rate < 0.1), in comparison to zero of 18,055
      autosomal and PAR genes (Fisher's exact P < 0.0001). Male-biased mutations in
      genes that escape X-inactivation were observed in combined analysis across many
      cancers and in several individual tumor types, suggesting a generalized
      phenomenon. We conclude that biallelic expression of EXITS genes in females
      explains a portion of the reduced cancer incidence in females as compared to
      males across a variety of tumor types.

PMID- 27869831
TI  - Normal-incidence reflectance difference spectroscopy based on a liquid crystal
      variable retarder.
AB  - We propose liquid crystal variable retarder-based reflectance difference
      spectroscopy for normal-incidence measurements. Principles, instrumentation, data
      collection and reduction, and calibration procedures are provided. The signal
      noise is better than 10<sup>-3</sup>, and the spectral range is from 1.6 to 2.4
      eV with 346 photon energy channels. As a demonstration, reflectance difference
      signals of a multilayer pentacene film on poly (ethylene terephthalate) (PET)
      film are presented with different polarization azimuths. The characteristic peaks
      at 1.8 and 1.97 eV, corresponding to the Davydov splitting of pentacene crystal,
      are observed, which indicate well-ordered in-plane anisotropic structure of
      pentacene crystal film on PET. Thanks to normal incidence, this design is immune
      to adjusting the optical structure for the measurements with different working
      distances, and the objective lens is easily integrated to realize microarea
      measurements.

PMID- 27869832
TI  - Generation of high contrast and high spatial quality idler from a low-gain
      optical parametric amplifier.
AB  - The temporal contrast of a regeneratively amplified, sub-picosecond pulse is
      enhanced by employing a low-gain optical parametric amplification stage self
      pumped by the second harmonic of the pulse. Through careful characterization of
      the two related nonlinear processes and optimization of the non-collinear
      geometry, a robust high-contrast idler pulse has been generated, with excellent
      spatial quality in both the near and far field. The overall energy conversion
      efficiency exceeds 14%, with 33% intensity conversion efficiency. The temporal
      cleaning is implemented without any bandwidth losses or spectral shift and
      produces approximately 20% temporal shortening. These experimental findings are
      in excellent agreement with numerical calculations.

PMID- 27869833
TI  - Single-ended mid-infrared laser-absorption sensor for simultaneous in situ
      measurements of H<sub>2</sub>O, CO<sub>2</sub>, CO, and temperature in combustion
      flows.
AB  - The development and demonstration of a four-color single-ended mid-infrared
      tunable laser-absorption sensor for simultaneous measurements of H<sub>2</sub>O,
      CO<sub>2</sub>, CO, and temperature in combustion flows is described. This sensor
      operates by transmitting laser light through a single optical port and measuring
      the backscattered radiation from within the combustion device. Scanned-wavelength
      modulation spectroscopy with second-harmonic detection and first-harmonic
      normalization (scanned-WMS-2f/1f) was used to account for variable signal
      collection and nonabsorption losses in the harsh environment. Two tunable diode
      lasers operating near 2551 and 2482 nm were utilized to measure H<sub>2</sub>O
      concentration and temperature, while an interband cascade laser near 4176 nm and
      a quantum cascade laser near 4865 nm were used for measuring CO<sub>2</sub> and
      CO, respectively. The lasers were modulated at either 90 or 112 kHz and scanned
      across the peaks of their respective absorption features at 1 kHz, leading to a
      measurement rate of 2 kHz. A hybrid demultiplexing strategy involving both
      spectral filtering and frequency-domain demodulation was used to decouple the
      backscattered radiation into its constituent signals. Demonstration measurements
      were made in the exhaust of a laboratory-scale laminar methane-air flat-flame
      burner at atmospheric pressure and equivalence ratios ranging from 0.7 to 1.2. A
      stainless steel reflective plate was placed 0.78 cm away from the sensor head
      within the combustion exhaust, leading to a total absorption path length of 1.56
      cm. Detection limits of 1.4% H<sub>2</sub>O, 0.6% CO<sub>2</sub>, and 0.4% CO by
      mole were reported. To the best of the authors' knowledge, this work represents
      the first demonstration of a mid-infrared laser-absorption sensor using a single
      ended architecture in combustion flows.

PMID- 27869834
TI  - Wide-bandgap nonlinear crystal LiGaS<sub>2</sub> for femtosecond mid-infrared
      spectroscopy with chirped-pulse upconversion.
AB  - Femtosecond time-resolved mid-infrared (MIR) spectroscopy based on chirped-pulse
      upconversion is a promising method for observing molecular vibrational dynamics.
      A quantitative study on nonlinear media for upconversion is still essential for
      wide applications, particularly at the frequencies below 2000  cm<sup>-1</sup>.
      We evaluate wide-bandgap nonlinear crystals of Li-containing ternary
      chalcogenides based on their performance as the upconversion medium for
      femtosecond MIR spectroscopy. The upconversion efficiency is measured as a
      function of the MIR pulse frequency and the chirped pulse energy.
      LiGaS<sub>2</sub> is found to be an efficient crystal for the upconversion of MIR
      pulses in a wide frequency range of 1100-2700  cm<sup>-1</sup>, especially below
      2000  cm<sup>-1</sup>. By using LiGaS<sub>2</sub> as an efficient upconversion
      crystal, we develop a MIR pump-probe spectroscopy system with a spectral
      resolution of 2.5  cm<sup>-1</sup>, a time resolution of 0.2 ps, and a probe
      window of 120  cm<sup>-1</sup>. Vibrational relaxation dynamics of CO stretching
      modes of Mn<sub>2</sub>(CO)<sub>10</sub> in cyclohexane and bovine serum albumin
      in D<sub>2</sub>O are demonstrated with a high signal-to-noise ratio.

PMID- 27869835
TI  - Variable diameter CO<sub>2</sub> laser ring-cutting system adapted to a zoom
      microscope for applications on polymer tapes.
AB  - This paper presents the conception and implementation of a variable diameter ring
      cutting system for a CO<sub>2</sub> laser with a working wavelength of 10.6 MUm.
      The laser-cutting system is adapted to an observation zoom microscope for
      combined use and is applicable for the extraction of small circular areas from
      polymer films, such as forensic adhesive tapes in a single shot. As an important
      characteristic for our application, the variable diameter ring-cutting system
      provides telecentricity in the target area. Ring diameters are continuously
      tunable between 500 MUm and 2 mm. A minimum width of less than 20 MUm was found
      for the ring profile edge. The basic characteristics of the system, including
      telecentricity, were experimentally evaluated and demonstrated by cutting
      experiments on different polymer tapes and further exemplary samples.

PMID- 27869830
TI  - Inactivation of Capicua drives cancer metastasis.
AB  - Metastasis is the leading cause of death in people with lung cancer, yet the
      molecular effectors underlying tumor dissemination remain poorly defined. Through
      the development of an in vivo spontaneous lung cancer metastasis model, we show
      that the developmentally regulated transcriptional repressor Capicua (CIC)
      suppresses invasion and metastasis. Inactivation of CIC relieves repression of
      its effector ETV4, driving ETV4-mediated upregulation of MMP24, which is
      necessary and sufficient for metastasis. Loss of CIC, or an increase in levels of
      its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse
      outcomes in people with lung and/or gastric cancer. Our findings reveal CIC as a
      conserved metastasis suppressor, highlighting new anti-metastatic strategies that
      could potentially improve patient outcomes.

PMID- 27869836
TI  - Active thermal fine laser tuning in a broad spectral range and optical properties
      of cholesteric liquid crystal.
AB  - In this study, we achieved active fine laser tuning in a broad spectral range
      with dye-doped cholesteric liquid crystal wedge-type cells through temperature
      control. The spatial pitch gradient of each position of the wedge cell at room
      temperature was almost maintained after developing a temperature gradient. To
      achieve the maximum tuning range, the chiral dopant concentration, thickness,
      thickness gradient, and temperature gradient on the wedge cell should be matched
      properly. In order to understand the laser tuning mechanism for temperature
      change, we studied the temperature dependence of optical properties of the
      photonic bandgap of cholesteric liquid crystals. In our cholesteric liquid
      crystal samples, when temperature was increased, photonic bandgaps were shifted
      toward blue, while the width of the photonic bandgap was decreased, regardless of
      whether the helicity was left-handed or right-handed. This is mainly due to the
      combination of decreased refractive indices, higher molecular anisotropy of
      chiral molecules, and increased chiral molecular solubility. We envisage that
      this kind of study will prove useful in the development of practical active
      tunable CLC laser devices.

PMID- 27869837
TI  - Ultra-flat supercontinuum generated from high-power, picosecond telecommunication
      fiber laser source.
AB  - An ultra-flat, high-power supercontinuum generated from a picosecond
      telecommunication fiber laser was presented. The pulse from a carbon nanotube
      mode-locked oscillator was amplified using an Er-Yb codoped fiber amplifier. The
      output of the system achieved an average power of 2.7 W, with the center
      wavelength at 1564 nm and a FWHM of 6 nm in the spectral domain. By passing this
      amplified high-power pulse through a 4.6 m highly nonlinear photonic crystal
      fiber, an ultra-flat supercontinuum spanning 1600-2180 nm is generated. And the
      average power of the supercontinuum achieves 1 W.

PMID- 27869838
TI  - Analytical comparison of pulses generated by locking three and five longitudinal
      modes in free-running class B lasers.
AB  - We consider the coherent oscillation of five longitudinal modes, which leads to
      the coupling of modes in the frequency domain and generation of short pulses in
      the time domain. The aim is to audit the mechanism of mode locking in more detail
      by extending the analytical solution of the Maxwell-Bloch equations of motion
      from three to five mode states. The characteristics of pulses including height,
      repetition, and duration have been calculated for a five-mode class B laser, and
      the changes are compared with respect to the three-mode state. The effects of
      other parameters, such as the mean damping rate of cavity mirrors, the frequency
      detuning of cavity longitudinal modes, and the laser pumping rate have also been
      investigated. The central and adjacent modes supply the energy of pulses. The
      amplification gains of five oscillating modes, together with the contribution to
      forming pulses, are evaluated. It is finally demonstrated that the results
      satisfy the energy conservation law.

PMID- 27869839
TI  - Investigation on iterative multiuser detection physical layer network coding in
      two-way relay free-space optical links with turbulences and pointing errors.
AB  - Physical layer network coding (PNC) improves the throughput in wireless networks
      by enabling two nodes to exchange information using a minimum number of time
      slots. The PNC technique is proposed for two-way relay channel free space optical
      (TWR-FSO) communications with the aim of maximizing the utilization of network
      resources. The multipair TWR-FSO is considered in this paper, where a single
      antenna on each pair seeks to communicate via a common receiver aperture at the
      relay. Therefore, chip interleaving is adopted as a technique to separate the
      different transmitted signals at the relay node to perform PNC mapping.
      Accordingly, this scheme relies on the iterative multiuser technique for
      detection of users at the receiver. The bit error rate (BER) performance of the
      proposed system is examined under the combined influences of atmospheric loss,
      turbulence-induced channel fading, and pointing errors (PEs). By adopting the
      joint PNC mapping with interleaving and multiuser detection techniques, the BER
      results show that the proposed scheme can achieve a significant performance
      improvement against the degrading effects of turbulences and PEs. It is also
      demonstrated that a larger number of simultaneous users can be supported with
      this new scheme in establishing a communication link between multiple pairs of
      nodes in two time slots, thereby improving the channel capacity.

PMID- 27869840
TI  - Tunable mode rotator for space-division multiplexing based on a few mode
      polarization maintaining fiber.
AB  - In this paper, a fiber-based tunable mode rotator is proposed and demonstrated by
      using the few mode-polarization maintaining fiber (FM-PMF). The mode
      birefringence in the FM-PMF causes phase difference between two orthogonal
      degenerate modes. With rotating the FM-PMF segment and getting a variation of
      aligning angle between the injected LP<sub>11</sub> (LP<sub>21</sub>) mode axis
      and FM-PMF axis, another intended LP<sub>11</sub> (LP<sub>21</sub>) mode with a
      certain orientation can be controllably generated at the FM-PMF output.

PMID- 27869841
TI  - Endlessly single-mode photonic crystal fiber as a high resolution probe.
AB  - We sample ultra-broadband light, focused onto a diffraction-limited spot, to an
      endlessly single-mode photonic crystal fiber (ESM) and detect both the field
      amplitude and phase using a SEA TADPOLE interferometer. We resolve spatial
      features up to 2.5 times finer than the fiber mode size while sampling the
      periodic features of the bipolar oscillating field in the transverse section. The
      resolution enhancement is expected also in other types of single-mode fibers in
      intensity measurements and leads to an inexpensive method for characterizing the
      point-spread function of such optical fields, e.g., diffraction-limited spots
      from microscope objectives. In addition, we demonstrate the guidance of a high-NA
      light field in the fine structure of an ESM fiber mode. The results are
      especially valuable for devices where a fiber tip acts as an input slit and
      defines the spatial resolution, e.g., fiber-based interferometers, spectrometers,
      and sensors.

PMID- 27869842
TI  - Fabrication of short-wavelength infrared dual-band-pass filter based on
      combination of Fabry-Perot filters.
AB  - Dual-band-pass filters are key optical components in dual-spectral detection
      applications; it is imperative to fabricate them in a relatively simple way for
      practical use. In this paper, a dual-band-pass filter working in short-wavelength
      infrared is developed by the combination of two Fabry-Perot (F-P) filters, each
      having a transparent band. These two filters are designed separately, and
      deposited at different sides of a substrate. The total layers' number of the dual
      band-pass filter is limited to 34; these layers are monitored by the method of
      direct transmittance level cut monitoring with a single monitor wavelength. The
      percent of optical extrema monitoring strategy is adopted in the deposition. The
      spectra of the F-P filters and the dual-band-pass filter are tested. The shorter
      pass-band's average transmittance is above 84%, the longer one is above 88%, and
      four of the pass-bands' edge steepness values are 1.4%,2.8%,1.9%, and 1.7%.

PMID- 27869844
TI  - Scintillations of higher order laser beams in anisotropic atmospheric turbulence.
AB  - The scintillation index of higher order laser beams is examined when such beams
      propagate in anisotropic atmospheric turbulence. Anisotropy is introduced through
      non-Kolmogorov atmospheric turbulence. The scintillation index results are
      obtained by employing the Rytov method solution; thus the results are valid for
      weak anisotropic atmospheric turbulence and for horizontal links. Variations in
      the scintillations are shown for various higher order laser modes against the
      changes in the optical source size, power law exponent of anisotropic non
      Kolmogorov spectrum, anisotropic factors, and link length. Our results can be
      used in the design of optical wireless communication systems used between
      airplanes.

PMID- 27869843
TI  - Effect of background dielectric on TE-polarized photonic bandgap of
      metallodielectric photonic crystals using Dirichlet-to-Neumann map method.
AB  - Using the Dirichlet-to-Neumann map method, we have calculated the photonic band
      structure of two-dimensional metallodielectric photonic crystals having the
      square and triangular lattices of circular metal rods in a dielectric background.
      We have selected the transverse electric mode of electromagnetic waves, and the
      resulting band structures showed the existence of photonic bandgap in these
      structures. We theoretically study the effect of background dielectric on the
      photonic bandgap.

PMID- 27869845
TI  - Angular velocity estimation based on star vector with improved current
      statistical model Kalman filter.
AB  - Angular velocity information is a requisite for a spacecraft guidance,
      navigation, and control system. In this paper, an approach for angular velocity
      estimation based merely on star vector measurement with an improved current
      statistical model Kalman filter is proposed. High-precision angular velocity
      estimation can be achieved under dynamic conditions. The amount of calculation is
      also reduced compared to a Kalman filter. Different trajectories are simulated to
      test this approach, and experiments with real starry sky observation are
      implemented for further confirmation. The estimation accuracy is proved to be
      better than 10<sup>-4</sup>  rad/s under various conditions. Both the simulation
      and the experiment demonstrate that the described approach is effective and shows
      an excellent performance under both static and dynamic conditions.

PMID- 27869846
TI  - Simultaneous measurement of refractive index distribution and topography by
      integrated transmission and reflection digital holographic microscopy.
AB  - We propose a method for simultaneously measuring dynamic changes of the
      refractive index distribution and surface topography, which integrates the
      transmission and reflection digital holographic microscopy based on polarization
      and angular multiplexing techniques. The complex amplitudes of the transmitted
      and reflected object waves can be simultaneously retrieved. The phase information
      of the reflected object wave is directly used to determine the topography of the
      specimen which corresponds to its physical thickness. Assuming that the
      refractive index distribution is uniform in the direction of the specimen
      thickness, the refractive index distribution can be deduced from the phase
      distributions of the transmitted and reflected object waves without any
      approximation. The refractive index distribution and dynamic changes of the
      topography of a tiny deionized water droplet have been measured for the
      availability of the proposed method.

PMID- 27869847
TI  - Sizing submicron particles from optical scattering data collected with oblique
      incidence illumination.
AB  - As submicron particles play an important role in a variety of ecosystems that
      include aqueous, terrestrial, and atmospheric, a measurement system to quantify
      them is highly desirable. In pursuit of formulating and fabricating a system to
      size them using visible light, a system that collects multi-directional scattered
      light from individual particles is proposed. A prototype of the system was
      simulated, built, and tested via calibration with a set of polystyrene spheres in
      water with known sizes. Results indicate that the system can accurately resolve
      the size of these particles in the 0.1 to 0.8 MUm range. The system incorporates
      a design that uses oblique illumination to collect scattered light over a large
      range of both forward and backward scatter angles. This is then followed by the
      calculation of a ratio of forward to backscattered light, integrated over a
      suitably defined range. The monotonic dependence of this ratio upon particle size
      leads to an accurate estimate of particle size. The method was explored first,
      using simulations, and followed with a working version. The sensitivity of the
      method to a range of relative refractive index was tested using simulations. The
      results indicate that the technique is relatively insensitive to this parameter
      and thus of potential use in the analysis of particles from a variety of
      ecosystems. The paper concludes with a discussion of a variety of pragmatic
      issues, including the required dynamic range as well as further research needed
      with environmentally relevant specimens to create a pragmatic instrument.

PMID- 27869848
TI  - Low-cost encoder using a phase shifting algorithm utilizing polarization
      properties of light.
AB  - In this work a novel polyphase optical encoder is presented, which uses a
      mathematical algorithm to take advantage of the polarization properties of light.
      This optical encoder has excellent accuracy, precision, and resolution in
      measuring the angular position of a shaft. Furthermore, it is designed to work
      with low-cost optical components. Initially, a light beam passes through a
      rotating polarizer, and readings are obtained from low-cost photoresistors
      located under phase shifted analyzers to generate characteristic curves for each
      of the phases, in the plane formed by the measured angle and the intensity of
      light. These curves are correlated to the ideal polarization curve formed by
      Malus' law via polynomial expressions to obtain the relationship between actual
      values and the ideal square cosine. After this characterization process, the
      encoder is ready for indefinite use, and operational data are introduced to a
      phase shifting algorithm, to obtain the angle position of any rotating device.

PMID- 27869849
TI  - Optical coherence tomography imaging of capillary reperfusion after ischemic
      stroke.
AB  - Although progress has been made for recanalization therapies after ischemic
      stroke, post-treatment imaging studies show that tissue reperfusion cannot be
      attained despite satisfactory recanalization in a significant percentage of
      patients. Hence, investigation of microcirculatory changes in both surface and
      deep cortical levels after ischemia reperfusion is important for understanding
      the post-stroke blood flow dynamics. In this study, we applied optical coherence
      tomography (OCT) imaging of cerebral blood flow for the quantification of the
      microcirculatory changes. We obtained OCT microangiogram of the brain cortex in a
      mouse stroke model and analyzed the data to trace changes in the capillary
      perfusion level (CPL) before, during, and after the stroke. The CPL changes were
      estimated in 1 and 2 h ischemia groups as well as in a non-ischemic sham-operated
      group. For the estimation of CPL, a decorrelation amplitude-based algorithm was
      implemented and used. As a result, the CPL considerably decreased during ischemia
      but recovered to the baseline when recanalization was performed 1 h after
      ischemia; however, the CPL was significantly reduced when recanalization was
      delayed to 2 h after ischemia. These data demonstrate that ischemia causes
      microcirculation dysfunction, leading to a decreased capillary reperfusion after
      recanalization. Microcirculatory no-reflow warrants more rigorous assessment in
      clinical trials, whereas advanced optical imaging techniques may provide
      mechanistic insight and solutions in experimental studies.

PMID- 27869850
TI  - Effects of particle locations on reconstructed particle images in digital
      holography.
AB  - The intensity and phase reconstructed from digital in-line holograms by the
      convolution approach are analyzed. Distortions of particle images depending on
      their position in the plane transverse to the optical axis are identified. For
      this purpose, the object fields of numerically simulated particle holograms as
      well as of experimental data are reconstructed. The results of three-dimensional
      correlations of numerical and experimental data are superior when the numerically
      generated reference volumes are adapted to the transverse locations of the
      particle. Thus, proof is given that the characteristics of a particle image
      change distinctly with the transverse position of the particle and that the
      numerical model successfully simulates these changes. Hence, this knowledge can
      be integrated in future particle position detection algorithms.

PMID- 27869851
TI  - Calibration of oblique-incidence reflectivity difference for label-free detection
      of a molecular layer.
AB  - Oblique-incidence reflectivity difference (OI-RD) is a form of polarization
      modulation ellipsometry that measures properties of thin films on a solid surface
      through the change in polarization state of light upon reflection from the
      surface. The measurement accuracy depends on the precision of the phase
      modulation amplitude and azimuthal alignments of key polarizing optical elements
      and, thus, requires careful calibration. In the present work, we describe robust
      methods of such calibrations that enable precise determination of the modulation
      amplitude and static retardation of a phase modulator and azimuths of key
      polarizing optics in an OI-RD system.

PMID- 27869852
TI  - Polarized transfer functions of the ocean surface for above-surface determination
      of the vector submarine light field.
AB  - A method is developed to determine the underwater polarized light field from
      above sea surface observations. A hybrid approach combining vector radiative
      transfer simulations and the Monte Carlo method is used to determine the transfer
      functions of polarized light for wind-driven ocean surfaces. Transfer functions
      for surface-reflected skylight and upward transmission of light through the sea
      surface are presented for many common viewing and solar geometries for clear-sky
      conditions. Sensitivity of reflection matrices to environmental conditions is
      examined and can vary up to 50% due to wind speed, 25% due to atmospheric aerosol
      load, and 10% due to radiometer field-of-view. Scalar transmission is largely
      independent of water type and varies a few percent with wind speed, while
      polarized components can change up to 10% in high winds. Considerations for
      determining the water-leaving radiance (scalar or vector) are discussed.

PMID- 27869853
TI  - Global calibration of unleveled theodolite using angular distance constraints.
AB  - The theodolite is an important optical measurement instrument in application. Its
      global calibration, including position and orientation, is a prerequisite for
      measurement. Most global calibration methods require the theodolite to be leveled
      precisely, which is time-consuming and susceptible to error. We propose a global
      calibration method without leveling: it solves position results using the angular
      distance of control points by nonlinear optimization and then computes
      orientation parameters (rotation matrix) linearly based on position results.
      Furthermore, global calibration of multiple theodolites is also introduced. In
      addition, we introduced a method that can compute the dip direction and tilt
      angle by decomposing the rotation matrix. We evaluate the calibration algorithms
      on both computer simulation and real data experiments, demonstrating the
      effectiveness of the techniques.

PMID- 27869829
TI  - Contribution of copy number variants to schizophrenia from a genome-wide study of
      41,321 subjects.
AB  - Copy number variants (CNVs) have been strongly implicated in the genetic etiology
      of schizophrenia (SCZ). However, genome-wide investigation of the contribution of
      CNV to risk has been hampered by limited sample sizes. We sought to address this
      obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094
      cases and 20,227 controls. A global enrichment of CNV burden was observed in
      cases (odds ratio (OR) = 1.11, P = 5.7 * 10-15), which persisted after excluding
      loci implicated in previous studies (OR = 1.07, P = 1.7 * 10-6). CNV burden was
      enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 * 10-11)
      and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 * 10-5). Genome-wide
      significant evidence was obtained for eight loci, including 1q21.1, 2p16.3
      (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2.
      Suggestive support was found for eight additional candidate susceptibility and
      protective loci, which consisted predominantly of CNVs mediated by nonallelic
      homologous recombination.

PMID- 27869854
TI  - Experimental investigation on supercontinuum generation by single, dual, and
      triple wavelength pumping in a silica photonic crystal fiber.
AB  - We investigate the supercontinuum (SC) generation in an 1 cm long silica photonic
      crystal fiber (PCF) pumped by the pulse sources with single, dual, and triple
      wavelengths, respectively. The silica PCF has two zero-dispersion wavelengths at
      900 and 2620 nm, respectively. When pumped by a single wavelength, the SC
      spectral range covers about 1000 nm. When pumped by dual and triple wavelengths,
      the SC spectral range covers wider than 2000 nm. Both the SC spectral range and
      the flatness are improved obviously when pumped by triple wavelengths. The
      maximum SC spectral range is obtained when the silica PCF is pumped by the triple
      wavelengths at 800, 1450, and 1785 nm. The SC spectral range covers 2810 nm from
      350 to 3160 nm wider than three octaves. The 10 dB bandwidth covers 2280 nm from
      450 to 2730 nm wider than two octaves. This is the first investigation on
      comparison of the SCs generated by different pump wavelengths up to three
      experimentally. The generated SC spectra have covered the full transmission
      window of silica fiber.

PMID- 27869855
TI  - Analytical and simulation results of a triple micro whispering gallery mode probe
      system for a 3D blood flow rate sensor.
AB  - The whispering gallery mode (WGM) is generated by light propagating within a
      nonlinear micro-ring resonator, which is modeled and made by an InGaAsP/InP
      material, and called a Panda ring resonator. An imaging probe can also be formed
      by the micro-conjugate mirror function for the appropriate Panda ring parameter
      control. The 3D WGM probe can be generated and used for a 3D sensor head and
      imaging probe. The analytical details and simulation results are given, in which
      the simulation results are obtained by using the MATLAB and Optiwave programs.
      From the obtained results, such a design system can be configured to be a thin
      film sensor system that can contact the sample surface for the required
      measurements The outputs of the system are in the form of a WGM beam, in which
      the 3D WGM probe is also available with the micro-conjugate mirror function. Such
      a 3D probe can penetrate into the blood vessel and content, from which the time
      delay among those probes can be detected and measured, and where finally the
      blood flow rate can be calculated and the blood content 3D image can also be seen
      and used for medical diagnosis. The tested results have shown that the blood flow
      rate of 0.72-1.11  MUs<sup>-1</sup>, with the blood density of 1060  kgm<sup>
      3</sup>, can be obtained.

PMID- 27869856
TI  - Recursive method for phase retrieval using transport of intensity and its
      applications.
AB  - Propagation of optical fields is governed by the Helmholtz equation or the
      paraxial wave equation. Transport of intensity is a noninterferometric method to
      find the phase of an object by recording optical intensities at different
      distances of propagation. The transport of intensity equation results from the
      imaginary part of the complex paraxial wave equation and is equivalent to the
      principle of conservation of energy. The real part of the paraxial wave equation
      yields the Eikonal equation in the presence of diffraction. The amplitude and
      phase of the optical field must therefore simultaneously satisfy both the real
      and imaginary parts of the paraxial wave equation during propagation. In this
      paper, we demonstrate, with illustrative examples, how to exploit this to
      retrieve the phase through recursive calculations of the phase and intensity.
      This is achieved using the transport of intensity equation, which is solved using
      standard techniques, and the real part of the paraxial wave equation, or the
      transport of phase equation, which is solved using a Gauss-Seidel iterative
      method. Examples include calculation of the imaged phase induced through self
      phase modulation of a focused laser beam in a liquid and the imaged phase of
      light reflected from a surface, which yields the 3D surface profile.

PMID- 27869857
TI  - Increasing the collection efficiency of time-correlated single-photon counting
      with single-photon avalanche diodes using immersion lenses.
AB  - Single-photon avalanche diodes (SPADs) achieving high timing resolution (~20-50 
      ps) developed for time-correlated single-photon counting (TCSPC) generally have
      very small photosensitive areas (25-100 MUm in diameter). This limits the
      achievable photon counting rate and signal-to-noise ratio and may lead to long
      counting times. This is detrimental in applications requiring several
      measurements, such as fluorescence lifetime imaging (FLIM) microscopy, which
      requires scanning, and time-domain diffuse optical tomography (TD-DOT). We show
      in this work that the use of an immersion lens directly affixed onto the
      photosensitive area of the SPAD helps alleviate this problem by allowing more
      light to be concentrated onto the detector. Following careful optical design and
      simulations, our experimental results show that it is actually possible to
      achieve the predicted theoretical increase in the photon counting rate (we
      achieve a factor of ~4 here). This work is of high relevance in high timing
      resolution TCSPC with small photosensitive area detectors and should find
      widespread interest in FLIM and TD-DOT with SPADs.

PMID- 27869858
TI  - Method for large-range structured light system calibration.
AB  - Structured light system calibration often requires the usage of a calibration
      target with a similar size as the field of view (FOV), which brings challenges to
      a large-range structured light system calibration since fabricating large
      calibration targets is difficult and expensive. This paper presents a large-range
      system calibration method that does not need a large calibration target. The
      proposed method includes two stages: (1) accurately calibrate intrinsics (i.e.,
      focal lengths and principle points) at a near range where both the camera and
      projector are out of focus, and (2) calibrate the extrinsic parameters
      (translation and rotation) from camera to projector with the assistance of a low
      accuracy, large-range three-dimensional (3D) sensor (e.g., Microsoft Kinect). We
      have developed a large-scale 3D shape measurement system with a FOV of 1120 
      mm*1900  mm*1000  mm. Experiments demonstrate our system can achieve measurement
      accuracy as high as 0.07 mm with a standard deviation of 0.80 mm by measuring a
      304.8 mm diameter sphere. As a comparison, Kinect V2 only achieved mean error of
      0.80 mm with a standard deviation of 3.41 mm for the FOV of measurement.

PMID- 27869859
TI  - Simulations of the gain profile and performance of a diode side-pumped QCW Nd:YAG
      laser.
AB  - A design of a diode side-pumped Nd:YAG laser module and simulations of the gain
      distribution inside the active medium are presented in this paper. The code is
      based on a nonsequential ray-tracing Monte Carlo method for the light generated
      by the laser diodes. The fluorescence image of the active medium was analyzed in
      order to compare it with the simulations, which were found to be in good
      agreement with experimental data. The laser was tested in QCW mode and provided a
      maximum average power of 220 W while maintaining constant energy per pulse in the
      100-1000 Hz range.

PMID- 27869861
TI  - Compressive spectral testbed imaging system based on thin-film color-patterned
      filter arrays.
AB  - Compressive spectral imaging systems can reliably capture multispectral data
      using far fewer measurements than traditional scanning techniques. In this paper,
      a thin-film patterned filter array-based compressive spectral imager is
      demonstrated, including its optical design and implementation. The use of a
      patterned filter array entails a single-step three-dimensional spatial-spectral
      coding on the input data cube, which provides higher flexibility on the selection
      of voxels being multiplexed on the sensor. The patterned filter array is designed
      and fabricated with micrometer pitch size thin films, referred to as pixelated
      filters, with three different wavelengths. The performance of the system is
      evaluated in terms of references measured by a commercially available
      spectrometer and the visual quality of the reconstructed images. Different
      distributions of the pixelated filters, including random and optimized
      structures, are explored.

PMID- 27869860
TI  - Quantitative-phase microscopy of nanosecond laser-induced micro-modifications
      inside silicon.
AB  - Laser-induced permanent modification inside silicon has been recently
      demonstrated by using tightly focused nanosecond sources at a 1550 nm wavelength.
      We have developed a quantitative-phase microscope operating in the near-infrared
      domain to characterize the laser-induced modifications deep into silicon. By
      varying the number of applied laser pulses and the energy, we observe porous and
      densified regions in the focal region. The observed changes are associated with
      refractive index variations |Deltan| exceeding 10<sup>-3</sup>, enough to
      envision the laser writing of optical functionalities inside silicon.

PMID- 27869862
TI  - Polarization control strategy of a laser communication terminal with a periscopic
      scanner using dual rotating waveplates.
AB  - We assessed the problem of low mixing efficiency caused by unstable signal
      polarization because of a moving reflector in a laser communication terminal with
      a periscopic scanner. A real-time polarization compensation method based on
      rotating waveplates is presented, which keeps the receiving signal light
      polarization at 45 degrees  linear polarized and improves system mixing
      efficiency. A geometric model of the laser communication terminal was first
      established, its polarization transmission characteristics were analyzed by three
      dimensional polarization tracks, and a system polarization transmission matrix
      was calculated. The relationship between scan angle and polarization of the
      output signal was simulated. The connections between a polarization-compensating
      lambda/4 waveplate and the lambda/2 waveplate rotation angle and scan angle were
      established. These findings will pave the way for real-time polarization control
      technology for coherent free-space laser communications.

PMID- 27869863
TI  - Small petal tools performance for parabolizing optical surfaces.
AB  - Small rigid petal tools, driven by a traditional polishing machine, were used to
      parabolize 20 mirrors 14 cm in diameter and 192 cm of curvature radius. Small
      rigid circular tools (SCTs), driven manually, were used to parabolize another 20
      identical surfaces. A Ronchi test with a square grid was used to evaluate the
      performance of both techniques. If small rigid petal tools are used, the surface
      quality, the reproducibility in the production process, and the time spent
      required to generate the surfaces are markedly better than using SCTs.

PMID- 27869864
TI  - Photomultiplier tube calibration based on Na lidar observation and its effect on
      heat flux bias.
AB  - Na lidar can measure vertical wind and temperature at high temporal and vertical
      resolutions, enough to resolve gravity wave perturbations. Heat flux due to
      dissipating gravity waves is an important quantity that can be derived from such
      perturbations. When lidar signals are high, a photomultiplier tube (PMT) used to
      count incoming photons may suffer from the saturation effect, and its output
      count is not linearly related to incoming photon counts. Corrections to this
      effect can be measured in a laboratory setting but may have large errors at high
      count rates. We show that the errors in the PMT correction can cause significant
      bias in the heat flux calculation due to the inherent correlation between wind
      and temperature errors. Using the measurements made by Na lidar at the Andes
      Lidar Observatory with Hamamatsu PMTs, we developed a calibration procedure to
      remove such PMT correction errors from laboratory measurements. By applying the
      revised PMT correction curve we demonstrated that the heat flux bias can be
      removed through this procedure.

PMID- 27869865
TI  - Multipass optical system for a Raman gas spectrometer.
AB  - In the present work, a multipass optical system intended for increasing the
      sensitivity of a Raman gas spectrometer based on the 90 degrees  geometry of
      scattered light collection is described. The system is characterized by an
      adjustment stability and an increased number of laser beams that pass through a
      small scattering volume, thus allowing the intensities of Raman signals from
      components of the gas medium in this volume to be increased. It is demonstrated
      that the application of this multipass optical system allows the sensitivity of
      the Raman gas spectrometer to be increased practically by 20 times (to several
      ppm for the 30-s registration time).

PMID- 27869866
TI  - Optical simulation of single-cell-gap transflective liquid crystal displays based
      on surface anchoring energy of periodical nano-grooved structures.
AB  - The single-cell-gap transflective liquid crystal display (TR-LCD) based on
      periodic distribution of surface anchoring energy (SAE) of periodical nano
      grooved structures is reported in this study. Different SAEs of planar-aligned
      nematic LC cells are associated with the threshold and operation voltages of the
      adopted LCs. Thus, according to the transmittance versus applied voltage curves,
      the regions with strong and weak SAEs in LC cells can be the transmission and
      reflection regions of a TR-LCD, respectively. According to the simulation results
      using 1D-DIMOS software, the phase retardation of a strong SAE region is
      approximately twice as large as that of a weak SAE region when a specific voltage
      is applied, and a suitable difference in SAE exists between these two regions.
      Moreover, various SAEs based on periodical nano-grooved structures can be
      fabricated to demonstrate the TR-LCD.

PMID- 27869868
TI  - ?

PMID- 27869867
TI  - Detection and identification of drugs under real conditions by using noisy
      terahertz broadband pulse.
AB  - We discuss an effective method for detecting and identifying drugs using a high
      noise terahertz (THz) signal. We add a noisy THz signal obtained in real
      conditions to the THz signal transmitted through a sample with the illicit drug
      methamphetamine. The insufficiency of the standard THz time-domain spectroscopy
      method is demonstrated, showing that this method detects the spectral features of
      neutral substances and explosives in a noisy THz signal. The method discussed is
      based upon time-dependent integral correlation criteria calculated using spectral
      dynamics of the medium response. We propose a modification of the integral
      correlation criterion that is less dependent on the spectral characteristics of a
      noisy signal under investigation.

PMID- 27869869
TI  - ?

PMID- 27869870
TI  - [Give birth in Italy is a "surgical" procedure.]
AB  - In Italy, the use of caesarean section has reached alarming levels: it involves
      more than one woman in three, as compared to one woman in five in Sweden and
      Finland. There is also considerable variability between different regions and
      different hospitals with clear heterogeneous access to appropriate interventions.
      In particular, although cesarean section rates are generally higher in the south,
      the heterogeneity between hospitals is much wider than the heterogeneity between
      regions, showing that the organizational and professional characteristics of
      individual providers strongly influence this phenomenon. In conclusion, in Italy
      structural peculiarities, organizational and professional supply of health
      services seem to influence the use of caesarean section more strongly than
      women's health conditions and pregnancy characteristics.

PMID- 27869871
TI  - The impact of academic conferences and how to make them useful.
AB  - Academic conferences have to date largely evaded empirical examination, despite
      demanding a lot of time and effort from those attending. Based on my work for a
      forthcoming book, I consider examples of conferences, including the Cochrane
      Colloquium, that provide important lessons from which we can learn about the
      impact of conferences. Travel to the conference, the venue, and when it is held
      can be a barrier to delegates attending, impacting on what will be said and
      discussed. By sharing new knowledge and wisdom, conferences act as a signal that
      cuts through the noise and adds to the "Knowledge Enterprise". But if the
      delegates are too tired from travel or do not attend, it is not possible to
      meaningfully discuss issues. There is a need for the evolving discipline of Meta
      research to examine research conferences, and for academics to discuss and
      challenge the role and value, and usefulness ofacademic conferences.

PMID- 27869872
TI  - [Towards DSM 5.1. Proposals for schizophrenia.]
AB  - Schizophrenia is a debilitating illness, present in approximately 1% of the
      global population. It is manifested through positive symptoms including
      delusions, hallucinations, disorganized thoughts and negative symptoms such as
      avolition, alogia, and apathy. In 2013 the 5th edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-5) has been released and some changes
      were introduced to make diagnosis of schizophrenia more accurate and precise, but
      researchers are already studying how to improve again the diagnostic criteria of
      this disorder. To this regard, we hypothesize two types of schizophrenia: poor
      adherence and good adherence to treatment schizophrenia. Our supposition is based
      on the evidence of reduced relapses, rehospitalisations, and better long-term
      course of illness in those patients with schizophrenia who are non-adherent to
      treatment. Given that adherence to therapy strongly influences patients attitude
      to medication, quality of life, and subjective well-being, the hypothesis of
      introducing adherence as a new schizophrenia specifier is compelling.

PMID- 27869873
TI  - [Scientific editors in Italy: identity, certification and roles.]
AB  - This study is developed as part of the activities of the Italian Chapter of the
      European Association of Science Editors (EASE) with the aim to provide an
      overview of the Italian scientific publishing in biomedicine and highlight the
      need for professional training and certification. Even at European and
      international level, in fact, there is a general lack of training and
      accreditation programs for the certification of professional editors. After
      defining the editor's role (term that in the Italian language has a certain
      degree of ambiguity) and the different professionals involved in the publication
      process, the paper analyzes the biomedical production in Italy, reporting the
      results of a survey on professional associations, institutions, scientific
      societies, and others. Also reported are the results of a first hearing on views
      expressed by the publishers themselves. From this study the need of a
      constructive discussion with all stakeholders emerges not only to improve the
      quality of publications in the biomedical field, but also to enhance and
      recognize the editor's profession, both in Italy and in other countries.

PMID- 27869874
TI  - [Pharmacological treatment in adrenal Cushing's syndrome.]
AB  - ACTH-independent adrenal Cushing's syndrome is the least common form of
      endogenous hypercortisolism. Recently, advances in genetics have allowed the
      description of several forms different to pathogenetic etiology, morphostructural
      characteristics and evolution towards the hypercortisolism. Alongside these, the
      adrenocortical carcinoma is also frequently responsible of a hypercortisolism
      clinical picture. The availability of steroidogenesis inhibitors, such as
      metyrapone and ketoconazole, provides to endocrinologist a therapeutic chance
      against different metabolic disorders sustained by hypercortisolism. Mitotane, an
      adrenolitic compound, is used alone in adjuvant therapy or in combination with
      different chemotherapy drugs in the treatment of adrenocortical carcinoma and in
      the treatment of severe Cushing's syndrome.

PMID- 27869875
TI  - [The added value of information summaries supporting clinical decisions at the
      point-of-care.]
AB  - Evidence-based healthcare requires the integration of the best research evidence
      with clinical expertise and patients' values. International publishers are
      developing evidence-based information services and resources designed to overcome
      the difficulties in retrieving, assessing and updating medical information as
      well as to facilitate a rapid access to valid clinical knowledge. Point-of-care
      information summaries are defined as web-based medical compendia that are
      specifically designed to deliver pre-digested, rapidly accessible, comprehensive,
      and periodically updated information to health care providers. Their validity
      must be assessed against marketing claims that they are evidence-based. We
      periodically evaluate the content development processes of several international
      point-of-care information summaries. The number of these products has increased
      along with their quality. The last analysis done in 2014 identified 26 products
      and found that three of them (Best Practice, Dynamed e Uptodate) scored the
      highest across all evaluated dimensions (volume, quality of the editorial process
      and evidence-based methodology). Point-of-care information summaries as stand
      alone products or integrated with other systems, are gaining ground to support
      clinical decisions. The choice of one product over another depends both on the
      properties of the service and the preference of users. However, even the most
      innovative information system must rely on transparent and valid contents.
      Individuals and institutions should regularly assess the value of point-of-care
      summaries as their quality changes rapidly over time.

PMID- 27869876
TI  - [Smart-web support: a new tool to help information sharing in managing complex
      paediatric diseases. Study protocol.]
AB  - As devices for learning, smart-web support (SWS) multimedia hypertexts on the web
      now provide more versatile and interactive reading systems than those
      traditionally available in static printed texts. Designing similar tools for
      clinical practice would make complex scientific information easier to comprehend,
      and present the various therapeutic options to patients as minimally alarming
      graphical representations. In a pilot project we intend to produce a SWS tool for
      parents or tutors of children with primary differentiated thyroid cancer (DTC), a
      heretofore rare disease whose incidence has increased over recent years. The SWS
      hypertexts, "pre-digested" by the multidisciplinary team caring for these
      children, will be inserted in a single web page (canvas) including shared sheets
      explaining the best surgical options (decision aids). To make evidence-based
      information easier to understand and help information sharing, the decision aids
      will combine text and graphics. The canvas will store data for the multimedia
      files in a cloud storage system, opened via a link. To measure parents' and
      tutors' understanding and appreciation of the information provided on the web,
      the canvas will include questionnaires to investigate satisfaction, eventual
      barrier encountered, and type of surgical therapy chosen. The SWS tool should
      allow users to obtain all the information in a relatively short time and improve
      parents' and children's satisfaction with the surgical options proposed. The
      results obtained will be useful for developing similar SWS devices for other
      complex paediatric diseases.

PMID- 27869877
TI  - [Computerized decision support systems: EBM at the bedside].
AB  - INTRODUCTION: One of the aims of Evidence-Based Medicine is to improve quality
      and appropriateness of care by the expedition of the knowledge transfer process.
      Computerized Decision Support Systems (CDSSs) are computer programs that provide
      alerts to the prescribing doctor directly at the moment of medical examination.
      In fact, alerts are integrated within the single patient electronic health
      record. CDSS based on the best available and updated evidence and guidelines may
      be an efficient tool to facilitate the transfer of the latest results from
      clinical research directly at the bedside, thus supporting decision-making.
      OBJECTIVES: The CODES (COmputerized DEcision Support) trial is a research program
      funded by the Italian Ministry of Health and the Lombardy Region. It aims to
      evaluate the feasibility of the implementation of a CDSS at the hospital level
      and to assess its efficacy in daily clinical practice. METHODS: The CODES project
      includes two pragmatic RCTs testing a CDSS (i.e. the EBMeDS - MediDSS) in two
      large Italian hospitals: the first is a general hospital in Vimercate (Lombardy),
      the second is an oncologic research center in Meldola (Emilia Romagna). The CDSS
      supports a full spectrum of decisions: therapy, drug interactions, diagnosis, and
      management of health care services are covered by a hundreds of reminders.
      However only few reminders are activated per patient, highlighting crucial
      problems in the delivery of high-quality care. The two trials have similar design
      and primary outcome, the rate at which alerts detected by the software are
      resolved by a decision of the clinicians. The project also includes the
      assessment of barriers and facilitators in the adoption of these new technologies
      by hospital staff members and the retrospective evaluation of the repeated risks
      in prescription habits. RESULTS: The trials are ongoing and currently more than
      10,000 patients have been randomized. The qualitative analysis revealed a
      progressive shift in the perception of the tool. Doctors are now seeing it as a
      trusted second opinion, available 24/7, which is tailored to the needs of the
      patient. The retrospective analysis showed the opportunity to achieve a better
      healthcare quality through an active risk management. Aggregating data from whole
      hospitals emerge rare drug interactions that otherwise would not be recognizable.
      DISCUSSION: CDSS are promising tools to support clinicians in everyday practice.
      They can be used as a real time app or to perform retrospective analyses. These
      data can provide unique resources to hospital management.

PMID- 27869878
TI  - [Efficacy and effectiveness of prevention programs in the population: for a more
      rational choice of public health interventions.]
AB  - INTRODUCTION: Evidence Based Prevention is becoming increasingly important to
      guide the policy-makers to choose preventive interventions to be offered to the
      population. Sometimes however the impact of an intervention in real conditions
      (effectiveness) may be smaller than the efficacy estimated in studies conducted
      in experimental settings. This can be due for example to suboptimal coverage of
      the intervention or to poor compliance of the involved subjects. Regrettably,
      this aspect is rarely taken into account in the planning of preventive
      interventions. To evaluate the discrepancy between efficacy and effectiveness of
      prevention programs we used as examples two interventions for smoking cessation
      currently available in Italy: 1) Interventions offered by Smoking Cessation
      Centers; 2) "Minimal Advice" provided by family doctors. METHODS: Using
      epidemiological data we estimated the expected effectiveness of interventions
      under different scenarios. RESULTS: Even assuming that Smoking Cessation Centers
      always offer the best available intervention (efficacy: 82%), they do not seem
      able to have a major effect on smoking cessation in the population
      (effectiveness: 0.8%). This is due to the very small number of smokers that seek
      help to these centers (1%). On the contrary, interventions based on minimal
      advice are anticipated to have much higher effectiveness (21%). CONCLUSION:
      Evidence of efficacy of an intervention is not sufficient to ensure that this
      will have a significant impact on health. The decision to implement a preventive
      action should be preceded by a careful evaluation of the expected effectiveness
      and be followed by a post-implementation monitoring to estimate the real impact
      of the intervention.

PMID- 27869879
TI  - [Near-decisions undertaken by clinical nurses in their daily practice: a concept
      analysis.]
AB  - In recent years, nursing autonomy has increased: clinical nurses in their daily
      practice undertake several independent and collaborative decisions. In addition,
      during nursing surveillance, clinical nurses collect data, intercept signs and/or
      symptoms of decline, early detect emerging problems and trigger a decision-making
      process by identifying interventions that lead to the attention of physicians, in
      advance - in order to be allowed to undertake the intervention; or after having
      implemented the intervention - in order to get an endorsement. The "near-decision
      making" process in a non-nursing field of autonomy, daily occurs, as a complex
      process that involves several aspects: individual, interpersonal, and
      organizational factors. To fill in the literature gap, a purposeful sample of
      expert nurses has been interviewed; then, using the hybrid model of Schwartz
      Barcott & Kim, the concept of "near-decision making" has been described, as well
      as its attributes, antecedents and consequences were identified.

PMID- 27869880
TI  - [Organizational ethnography of direct drugs distribution in Parma AUSL.]
AB  - The locations where healthcare organizations directly distribute medications to
      patients in specific circumstances, such as at hospital discharge, are settings
      at risk of professional errors. Using organizational ethnography methodology, we
      sought to explore the characteristics of points of direct distribution of drugs
      (PDD) in the AUSL of Parma and identify aspects of the delivery process that
      could potentially generate errors. We conducted 75 3-hour observations (225 hours
      at total) of the two Parma AUSL PDDs. The nature of the observations was known by
      PDD professionals but blinded to PDD patients. In one PDD, we shadowed the
      pharmacist responsible for the entire drug distribution process, as well as
      followed the pattern of drug packaging from the Centralized Logistic Pharmacy
      Unit in Reggio Emilia to the Parma Pharmaceutical Department. In the other PDD,
      we carried out observations in the patient waiting room and conducted interviews
      with patients and PDD professionals. Collected data were evaluated via content
      analysis and study results were presented to the study-working group for further
      discussion. Research findings highlighted a limited number of errors in drug
      delivery process. The most frequently observed errors by pharmacists were
      incorrect interpretation of prescriptions, dispensation of wrong dosage, and
      failure to deliver a prescribed drug to the patient. Potential sources of error
      were repeated interruptions of the pharmacist workflow, such as phone calls,
      helping colleagues in emergency situations and serving an excessive number of
      patients. Based on these results, the study-working group proposed logistical and
      organizational modifications of PDD and delivery process to improve quality and
      reduce risks.

PMID- 27869881
TI  - [The art and science of engaging patients into medical research: using
      professional recruiters' experiences to inform physicians and scientific
      directors' strategic choices.]
AB  - In order to advance medical care, it is necessary to invest resources, both human
      and financial, in medical research. However, these investments sometimes are not
      sufficient to ensure the success of research studies. No progress can be made
      without the participation of patients in research studies and clinical trials.
      These potential participants are normally identified by their physicians, or by
      professional recruiters, depending on the patient clinical profile. However,
      often patients are intimidated by the idea of engaging in clinical trials for
      several reasons, including the fear of side effects, to the difficulty of
      understanding specific research-related terms. The main objective of this project
      was to identify the communication strategies used by recruiters to help patients
      enroll into medical research projects. Another goal of the study was to identify
      key information that would help PIs and researchers make more effective decisions
      in terms of design and methodology. A total of 11 focus groups were conducted in
      two large, ethnically diverse cities: Indianapolis and Miami (USA). Our analyses
      indicated that recruiters use a variety of verbal and nonverbal communication
      strategies to create a relationship with potential participants. In addition,
      recruiters consider the cultural background of the people they interact with, the
      environment in which they live, the resources available, and the possible support
      of family members.

PMID- 27869882
TI  - [Assessment of geriatric patients' care needs based on sosia classification: the
      reality of the lombardy region in nursing home.]
AB  - The increased demand to care that originates from demographic changes called in
      Italy a rapid development in Nursing Home with particular emergency the problem
      of programme the welfare response. It is essential the development of a
      classification system able to describe the stratification of the case mix on the
      basis of the care requirements, allowing a remuneration in function of the
      complexity care. Since 2003, the Lombardy region has introduced a case-mix
      reimbursement system for nursing homes based on the SOSIA form which classifies
      residents into eight classes of frailty. In the present study the agreement
      between SOSIA classification and other well documented instruments, including
      Barthel Index, Mini-Mental State Examination on the basis of three indicators
      (mobility, cognition, comorbidity) is evaluated in eight classes of frailty.
      However, it is not any research project was published in order to assess the
      agreement between SOSIA classification and other measuring instruments. Although
      various methods exist by which researchers have attempted to measure the need for
      nursing care, there is no nationally accepted system for determining the total
      amount of registered nursing resources required by residents in long-term care.
      The aim of this study was to evaluate the correlation between SOSIA and filing
      systems widely used, such as the degree of Barthel disability rating scale, the
      Mini-Mental State Examination to offer care appropriate for the case-mix. Only
      the higher complexity care has classified in the first two classes, while the
      remaining levels has categorized in the lowest paid. Misclassification therefore
      induces an underestimation of the real care needs and, consequently, inadequate
      remuneration.

PMID- 27869884
TI  - ?

PMID- 27869883
TI  - Punches and knocks to the physicians: choosing wisely or self protection?
AB  - A case of a normal delivery in which the obstetrician has been beaten and
      insulted without any reason by the patient' husband is reported. Patient' husband
      followed his personal, wrong, perspectives about the labour and delivery. As
      patients pretend from physicians unnecessary exams and procures irrespective from
      physicians' suggestions, the culprits of our failure in not following the
      "choosing wisely" are the patients.

PMID- 27869885
TI  - ?

PMID- 27869888
TI  - ?

PMID- 27869886
TI  - [ANMCO/ELAS/SIBioC Consensus document: Recommendations for the use of cardiac
      biomarkers in heart failure patients].
AB  - Biomarkers have dramatically impacted the way heart failure (HF) patients are
      evaluated and managed. A biomarker is a characteristic that is objectively
      measured and evaluated as an indicator of normal biological or pathogenic
      processes, or pharmacological responses to a therapeutic intervention.
      Natriuretic peptides (B-type natriuretic peptide [BNP] and N-terminal proBNP) are
      the gold standard biomarkers in determining the diagnosis and prognosis of HF,
      and a natriuretic peptide-guided HF management looks promising. In the last few
      years, an array of additional biomarkers has emerged, each reflecting different
      pathophysiological processes in the development and progression of HF: myocardial
      insult, inflammation, fibrosis and remodeling, but their role in the clinical
      care of the patient is still partially defined and more studies are needed before
      to be well validated. Moreover, several new biomarkers have the potential to
      identify patients with early renal dysfunction and appear to have promise to help
      the management cardio-renal syndrome.With different biomarkers reflecting HF
      presence, the various pathways involved in its progression, as well as
      identifying unique treatment options for HF management, a closer cardiologist
      laboratory link, with a multi-biomarker approach to the HF patient, is not far
      ahead, allowing the unique opportunity for specifically tailoring care to the
      individual pathological phenotype.

PMID- 27869887
TI  - [ANMCO Position paper: Hospital discharge planning].
AB  - Hospital discharge is often poorly standardized and is characterized by
      discontinuity and fragmentation of care, putting patients at high risk of post
      discharge adverse events and early readmission. The present ANMCO position paper
      reviews the modifiable components of the hospital discharge process related to
      adverse events or rehospitalizations and suggests the optimal methods for
      redesign the whole discharge process. The key principles for proper hospital
      discharge or transfer of care acknowledge that hospital discharge:- is not an
      isolated event, but a process that has to be planned immediately after admission,
      ensuring that the patient and the caregiver understand and contribute to the
      planned decisions as equal partners;- is facilitated by a comprehensive systemic
      approach that begins with a multidimensional evaluation process;- must be
      organized by an operator who is responsible for the coordination of all phases of
      the hospital patient pathway, involving afterwards the physician and transferring
      to them the information and responsibility;- is the result of an integrated
      multidisciplinary team approach;- uses appropriately the transitional and
      intermediate care services;- is carried out in an organized system of care and
      continuum of services;- programs the passage of information to after-discharge
      services.

PMID- 27869889
TI  - [ANMCO/SICP/SIGO Consensus document: Pregnancy and congenital heart disease].
AB  - The success of cardiac surgery over the past 50 years has increased numbers and
      median age of survivors with congenital heart disease (CHD). Adults now represent
      two-thirds of patients with CHD; in the United States alone the number is
      estimated to exceed 1 million.In this population many affected women reach
      reproductive age and wish to have children. While in many CHD patients pregnancy
      can be accomplished successfully, some special situations with complex anatomy,
      iatrogenic or residual pathology are associated with an increased risk of severe
      maternal and fetal complications. Pre-conception counseling allows women to come
      to truly informed choices. Risk stratification tools can also help high-risk
      women to eventually renounce to pregnancy and to adopt safe contraception
      options. Once pregnant, women identified as intermediate or high-risk should
      receive multidisciplinary care involving a cardiologist, an obstetrician and an
      anesthesiologist with specific expertise in managing this peculiar medical
      challenge.This document is intended to provide cardiologists working in hospitals
      where an Obstetrics and Gynecology Department is available with a streamlined and
      practical tool, useful for them to select the best management strategies to deal
      with a woman affected by CHD who desires to plan pregnancy or is already
      pregnant.

PMID- 27869890
TI  - [ANMCO/SIC/SICI-GISE/SICCH Consensus document: Risk stratification in elderly
      patients undergoing cardiac surgery and transcatheter aortic valve implantation].
AB  - Aortic stenosis is one the most frequent valvular diseases in developed
      countries, and its impact on public healthcare resources and assistance is
      increasing. A substantial proportion of elderly patients with severe aortic
      stenosis is frequently not eligible for surgery because of advanced age, frailty
      and multiple comorbidities. Transcatheter aortic valve implantation (TAVI)
      enables the treatment of very elderly patients at high or prohibitive surgical
      risk considered ineligible for surgery and with an acceptable life expectancy.
      However, a significant proportion of patients die or do not achieve an
      improvement of quality of life in the short to medium-term follow-up. It is
      important to determine: 1) whether and how much patient frailty influences the
      procedural risk; 2) whether quality of life and the individual patient survival
      are influenced by aortic valve disease alone or by other associated factors; 3)
      whether a geriatric specialist intervention to evaluate and correct other
      diseases with their potential or already evident disabilities can improve the
      results of TAVI, in particular patient quality of life. Consequently, in addition
      to risk stratification with conventional tools, a number of factors including
      multimorbidity, disability, frailty and cognitive function should be considered
      in order to assess the expected benefit of TAVI. Preoperative optimization
      through a multidisciplinary approach with a Heart Team can counteract the
      multiple damage (cardiac, neurological, muscular, respiratory, renal) that can
      potentially worsen the reduced physiological reserves characteristic of frailty.
      The systematic implementation into clinical practice of multidimensional
      assessment instruments of frailty and cognitive function for screening and
      exercise, and the adoption of specific care pathways should facilitate this task.

PMID- 27869891
TI  - [ANMCO Position paper: Direct new oral anticoagulants for the prevention of
      thromboembolic complications in patients with atrial fibrillation: clinical
      scenarios and future perspectives].
AB  - It is now 4 years since the introduction of the new direct oral anticoagulants
      into clinical practice. Therefore, the Italian Association of Hospital
      Cardiologists (ANMCO) has deemed necessary to update the previous position paper
      on the prevention of thromboembolic complications in patients with non-valvular
      atrial fibrillation, which was published in 2013. All available scientific
      evidence has been reviewed, focusing on data derived from both clinical trials
      and observational registries. In addition, all issues relevant to the practical
      clinical management of oral anticoagulation with the new direct inhibitors have
      been considered. Specific clinical pathways for optimal use of oral
      anticoagulation with the new directly acting agents are also developed and
      proposed for clinical implementation. Special attention is finally paid to the
      development of clinical algorithms for medium and long-term follow-up of patients
      treated with new oral direct anticoagulants.

PMID- 27869895
TI  - [The LEADLESS II and Micra studies].

PMID- 27869893
TI  - [ANMCO Position paper: Recommendations for the follow-up of patients with
      pulmonary thromboembolism].
AB  - Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary
      embolism, is the third most common cause of cardiovascular death. The management
      of the acute phase of VTE is well described in several papers and guidelines,
      whereas the management of the follow-up of the patients affected from VTE is less
      defined. This position paper of the Italian Association of Hospital Cardiologists
      (ANMCO) tries to fill the gap using currently available evidence and the opinion
      of the experts to suggest the most useful way to manage patients in the chronic
      phase.The clinical and laboratory tests acquired during the acute phase of the
      disease drives the decision of the following period. Acquired or congenital
      thrombophilic factors may be identified to explain an apparently not provoked
      VTE. In some patients, a not yet clinically evident cancer could be the trigger
      of VTE and this could lead to a different strategy. The main target of the post
      acute management is to prevent relapse of the disease and to identify those
      patients who could worsen or develop chronic thromboembolic pulmonary
      hypertension. The knowledge of the etiopathogenetic ground is important to
      address the therapeutic approach, choosing the best antithrombotic strategy and
      deciding how long therapy should last. During the follow-up period, prognostic
      stratification should be updated on the basis of new evidences eventually
      acquired.Treatment of VTE is mainly based on oral or parenteral anticoagulation.
      Oral direct inhibitors of coagulation represent an interesting new therapy for
      the acute and extended period of treatment.

PMID- 27869892
TI  - [ANMCO position paper: Use of new oral anticoagulants for the treatment and
      prevention of pulmonary thromboembolism].
AB  - The new oral anticoagulants (NOACs) have radically changed the approach to the
      treatment and prevention of thromboembolic pulmonary embolism. The authors of
      this position paper face, in succession, issues concerning NOACs, including 1)
      their mechanism of action, pharmacodynamics and pharmacokinetics; 2) the use in
      the acute phase with the "double drug single dose" approach or with "single drug
      double dose"; 3) the use in the extended phase with demonstrated efficacy and
      with low incidence of bleeding events; 4) the encouraging use of NOACs in
      particular subgroups of patients such as those with cancer, the ones under- or
      overweight, with renal insufficiency (creatinine clearance >30 ml/min), the
      elderly (>75 years); 5) they propose a possible laboratory clinical pathway for
      follow-up; 6) carry out an examination on the main drug interactions, their
      potential bleeding risk, and the way to deal with some bleeding complications.
      The authors conclude that the use of NOACs both in the acute phase and in the
      extended phase is equally effective to conventional therapy and associated with
      fewer major bleeding events, which make their use in patients at higher risk of
      recurrences safer.

PMID- 27869896
TI  - [The position statement from the Taskforce on Takotsubo Syndrome of the European
      Society of Cardiology: new insights and the Italian contribution].

PMID- 27869897
TI  - [The five most important novelties in the 2015 ESC guidelines for the management
      of acute coronary syndromes in patients presenting without persistent ST-segment
      elevation].

PMID- 27869898
TI  - [Takotsubo cardiomyopathy: current evidence from observational studies and
      pathophysiological background].
AB  - Takotsubo cardiomyopathy is an acute reversible form of cardiac failure, firstly
      described in 1991, with a prognosis not favorable as previously thought. Although
      high levels of catecholamines have been suggested as the leading mechanism for
      the onset, the pathophysiology remains unclear. However, several
      pathophysiological explanations have been proposed, all not mutually exclusive. A
      complex chain of events is present, including the activation of the hypothalamic
      pituitary-adrenal axis, the surge in circulating catecholamines and subsequent
      cardiovascular responses. This review addresses the diagnostic classification,
      short and mid-term prognosis, precipitating factors, classification into primary
      and secondary forms, and possible drug therapies for stress cardiomyopathy.
      Clinical and experimental studies are needed to further improve diagnosis and
      targeted therapies.

PMID- 27869899
TI  - [Patients with non-ST-elevation acute coronary syndrome managed without coronary
      revascularization: an undertreated population].
AB  - Non-ST-elevation acute coronary syndromes (NSTE-ACS) represent one of the most
      common clinical presentations of ischemic heart disease. Patients with NSTE-ACS
      are a heterogeneous population, with different clinical features and prognosis. A
      significant proportion of this population is medically managed, without any
      revascularization. In the Italian EYESHOT and French FAST-MI registries, patients
      managed with a conservative strategy were 40% and 35%, respectively. NSTE-ACS
      patients not undergoing coronary revascularization are at higher risk of adverse
      cardiovascular events and have a worse prognosis, including short- and long-term
      mortality, compared with those receiving revascularization. Patients with NSTE
      ACS medically managed consist of three different subgroups: those not undergoing
      coronary angiography, those receiving coronary angiography and without
      significant coronary artery disease, and those with significant coronary artery
      disease at angiography but not receiving revascularization. Patients presenting
      with NSTE-ACS for whom a conservative strategy without coronary angiography is
      planned should be selected very carefully and coronary angiography should not be
      denied because of the lack of on-site cath-lab facilities. In addition, advanced
      age alone, in the absence of severe comorbidities or frailty, should not be
      considered as a reason for denying coronary angiography and, in general, optimal
      treatment. Given that evidence-based data are lacking, a careful balance between
      benefits and risks is needed in the decision to perform or not coronary
      angiography and/or revascularization in patients with important comorbidities, or
      frailty, or advanced age. In this decisional process, it should be also taken
      into consideration the role of coronary anatomy in risk stratification and
      treatment guidance.NSTE-ACS patients managed without revascularization less
      frequently receive guideline-recommended pharmacological treatment. Dual
      antiplatelet therapy is recommended for 12 months also in medically managed
      patients, after careful balance of ischemic and bleeding risk. Indeed, in this
      group of patients it is mandatory to optimize pharmacological treatment,
      including antiplatelet therapy, in order to improve clinical outcome. In NSTE-ACS
      not undergoing revascularization, the proportion of patients discharged with dual
      antiplatelet therapy should be increased in comparison to current clinical
      practice, and the use of ticagrelor instead of clopidogrel should be considered
      in selected patients.

PMID- 27869900
TI  - [Transient left ventricular apical ballooning with dynamic outflow tract
      obstruction complicated by persistent hypotension].
AB  - The pathogenesis of tako-tsubo syndrome remains, nowadays, unclear: it is likely
      that the relevance of the different proposed mechanisms differs among specific
      clinical contexts. In this paper, we describe the case of a 61-year-old woman
      admitted to the intensive cardiac care unit for pre-syncope and persistent
      hypotension. Clinical and echocardiographic data were suggestive of tako-tsubo
      syndrome with severe dynamic left ventricular outflow tract (LVOT) obstruction
      and severe mitral regurgitation. Coronary angiography was normal. Inotropic
      agents were not administered, because absolutely contraindicated in the presence
      of LVOT obstruction: indeed, they may worsen the dynamic gradient with further
      hemodynamic compromise. The patient was, therefore, initially treated with
      intravenous fluid infusion and, later on, with beta-blockers; the patient had a
      regular clinical recovery, with progressive disappearance of ECG and
      echocardiographic abnormalities. This case confirms that an early
      echocardiographic diagnosis of LVOT obstruction is essential for therapeutic
      decision-making, especially in the setting of tako-tsubo syndrome presenting with
      compromised hemodynamic status.

PMID- 27869901
TI  - [2015 ESC Guidelines for the management of acute coronary syndromes in patients
      presenting without persistent ST-segment elevation. Task Force for the Management
      of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment
      Elevation of the European Society of Cardiology (ESC)].

PMID- 27869902
TI  - [On the unpredictability of suicide].
AB  - Suicide has become one of the main reasons of professional liability proceedings
      for psychiatrists. It is a widespread belief that suicide is a systematic
      expression of mental illness and that, as for many diseases is preventable by
      appropriate means. There is a lack of research data that can enable the
      identification of clinically useful variables to identify suicide risk, even in
      people who have already made a suicide attempt. Unfortunately, these convictions
      have led and lead to judgments of professional responsibility for psychiatrists
      that are not based on scientific data, but on social needs related to feelings of
      frustration and helplessness that develop after a suicide and by the urge to
      compensate in some way the family of suicide victim. Suicide is too complex a
      phenomenon to be reported to a causality beyond any reasonable certainty as
      instead required by the criminal law, neither can be faced with a progressive
      patients loss of freedom of our patients.

PMID- 27869903
TI  - Approach to the patient hospitalized during the Muslim Ramadan: bioethical and
      clinical considerations.
AB  - Multi-ethnicity has been persuading the healthcare professionals to increasingly
      learn new tools in terms of cultural and socialskills, in order to cope with a
      diversified variety of patients. The coexistence of different cultures in Italy
      can be found in the migration flows over the last few decades. The cohabitations
      between individuals with different ethnicity in our territory has led the health
      professionals to address some anthropological, moral, religious and political
      issues implied in populations and cultures different from ours. Clinical
      literature has made us aware of the importance of correct communication between
      doctor and patient in order to determine the diagnostic-therapeutic plan,
      especially in the patients with a foreign origin due to the linguistic and
      intercultural differences implicated. In an emergency condition, it may occur to
      cure the patients neglecting their cultural identity and, in so doing, to create
      misunderstandings that, in turn, can lead to a lack of human relationship and
      frustrate the therapeutic project. An example is the treatment of Muslim people.
      The authors, through the description of a case observed during Ramadan, analyze
      the variables applying to the therapeutic decision making process.

PMID- 27869904
TI  - [Neural basis of social cognition in bipolar disorder].
AB  - AIM: This article review studies social and interpersonal functioning in patients
      with bipolar disorder (BD), and reports on the neurobiological underpinnings of
      the dysfunctions in emotion recognition, i.e. one of the main domains of social
      cognition. METHODS: A bibliographical research of controlled studies from 1967 to
      2015 was completed in PubMed and PsycINFO using the keywords: "fMRI", "emotion
      comprehension", "emotion perception", "affect comprehension", "affect
      perception", "facial expression", "prosody", "theory of mind", "mentalizing",
      "attributional style", "social perception", "empathy" and "bipolar disorder" or
      "unipolar depression". RESULTS: Limbic hyperactivity, with a lack of appropriate
      cortical control, has been reported in subjects with BD during social
      interactions. This is particularly evident during the acute affective episodes
      but may persist during the euthymic phases. DISCUSSION: Deficits in emotion
      regulation, including neural systems implicated both in voluntary and automatic
      emotion regulatory subprocesses, are present in DB, particularly for what
      pertains to social interactions and interpersonal functioning. CONCLUSIONS:
      Patients with bipolar disorder may present a dysfunction in the cortical ability
      to modulate the limbic system, which may show hyperactivity during social
      interactions. More studies are needed, including studies to evaluate treatment
      implications.

PMID- 27869905
TI  - Orthorexia nervosa in a sample of Italian university population.
AB  - AIM: To investigate frequency and characteristics of orthorexic behaviours in a
      large university population. METHODS: A total of 2826 individuals volunteered to
      complete an on-line anonymous form of ORTO-15 questionnaire, a self-administered
      questionnaire designed and validated to evaluate orthorexic symptomatology. As
      made in previous studies, an ORTO-15 total score lower than 35 has beenused as an
      optimal threshold to detect a tendency to orthorexia nervosa. A specifically
      designed form was also used to collect socio-demographic variables. RESULTS:
      Overall, 2130 students and 696 university employees belonging to University of
      Pisa (Italy) were assessed. Orthorexic features had a frequency of 32.7%. Females
      showed a significantly higher rate of over-threshold scores on ORTO-15, a lower
      BMI, a higher rate of underweight condition and of vegan/vegetarian nutrition
      style than males. DISCUSSION: Orthorexia nervosa defined as a "fixation on
      healthy food", is not formally present in DSM-5. The emergence of this condition
      as a new, possible prodromal of a psychological syndrome, has been recently
      emphasized by an increasing number of scientific articles. From our sample of
      university population emerged that being vegetarian or vegan, under-weight,
      female, student and being interested in the present study were significantly
      predictive of orthorexic tendency. CONCLUSIONS: Our data contribute to define the
      new conceptualization of orthorexia nervosa. Further studies are warranted in
      order to explore the diagnostic boundaries of this syndrome, its course and
      outcome, and possible clinical implications.

PMID- 27869906
TI  - [Emotional Intelligence Index: a tool for the routine assessment of mental health
      promotion programs in schools].
AB  - AIM: After critical examination of several aspects relating to the evaluation of
      some dimensions of emotional intelligence through self-assessment tools, is
      described the procedure of construction and validation of an Index for its
      measurement, conceived only for the routine assessment of health promotion
      programs mental in schools that include among their objectives the improvement of
      emotional intelligence specifically "outcome-oriented". METHODS: On the basis of
      the two most common international tools, are listed 27 items plus 6 of control,
      illustrated two Focus Group (FG) of students (face validity). The scale obtained
      by FG was administered to 300 students, and the results were submitted to
      factorial analysis (construct validity). It was also evaluated the internal
      consistency with Cronbach's Alpha and studied concurrent validity with the
      emotional quotient inventory, a scale of perceived self-efficacy and a stress
      test rating. RESULTS: From the analysis of FG all the original items were
      modified, deleted 4, and reduced the encoding system from 6 to 4 levels of Likert
      scale. Of the 23 items included in the analysis have emerged five factors (intra
      psychic dimension, interpersonal, impulsivity, adaptive coping, sense of self
      efficacy) for a total of 15 items. Very satisfactory were the results of the
      validation process of internal consistency (0.72) and the concurrent validity.
      CONCLUSIONS: The results are positive. It is obtained in fact the shortest
      routine assessment tool currently available in Italy which constitutes a real
      Index, for which compilation are required on average 3 minutes. Is emphasized the
      characteristic of an Index, and not of questionnaire or interview for clinical
      use, highlighting the only specific use for mental health promotion programs in
      schools.

PMID- 27869907
TI  - Validation of the Gambling Disorder Screening Questionnaire, a self-administered
      diagnostic questionnaire for gambling disorder based on the DSM-5 criteria.
AB  - AIM: The DSM-5 has modified the diagnostic criteria for gambling disorder,
      compared to the fourth edition of the manual; new diagnostic instruments are
      therefore needed. This study evaluated the psychometric characteristics of the
      Gambling Disorder Screening Questionnaire (GDSQ), a self-report questionnaire
      based on the DSM-IV and DSM-5 criteria for Gambling Disorder, measuring its
      validity, internal consistency, and submitting the questionnaire to a principal
      components analysis. METHODS: 71 patients from a gambling disorder outpatient
      clinic and 70 controls were evaluated with the GDSQ, the South Oaks Gambling
      Screen (SOGS), and a psychiatric interview. RESULTS: The test showed a good
      sensibility, specificity, internal consistency, concurrent validity with the
      SOGS. The exclusion of the "illegal acts" item, and the lowering of the cut-off
      score to four positive items, as suggested by the DSM-5 criteria, improved the
      test sensibility and internalconsistency. DISCUSSION AND CONCLUSIONS: The GDSQ
      can be considered a useful screening test for Gambling Disorder. Furthermore,
      this study confirms the improved diagnostic accuracy of the criteria listed in
      the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders,
      compared to the previous edition.

PMID- 27869908
TI  - ?

PMID- 27869909
TI  - Altered levels of circulating cytokines and microRNAs in lean and obese
      individuals with prediabetes and type 2 diabetes.
AB  - Today obesity and type 2 diabetes (T2D) have both reached epidemic proportions.
      However, our current understanding of the primary mechanisms leading to these
      diseases is still limited due to the complex multifactorial nature of the
      underlying phenomena. We hypothesize that the levels of specific cytokines and
      miRNAs vary across the diabetes spectrum and unique signatures associated with
      them may serve as early biomarkers of the disease and provide insights into
      respective pathogenetic mechanisms. In this study, we measured the circulating
      levels of cytokines and microRNAs (miRNAs) in lean and obese humans with
      prediabetes (n = 21), T2D (n = 17), and healthy controls (n = 20) (ORIGINS trial,
      NCT02226640). Data were analyzed by fitting linear models adjusted for
      confounding variables (BMI, age, and gender in the diabetes context and age,
      gender, and diabetes status in the obesity context) and implementing
      nonparametric randomization-based tests for statistical inference. Group
      differences and correlations (r > 0.3) between variables with P < 0.05 were
      considered significant. False discovery rates (FDR) correcting for multiple
      testing were calculated using the Benjamini-Hochberg correction. We found a
      number of circulating cytokines and miRNAs deregulated in subjects with obesity,
      prediabetes, and T2D. Specifically, cytokines IL-6, IL-8, IL-10, IL-12, and
      SFRP4, as well as miRNAs miR-21, miR-24.1, miR-27a, miR-28-3p, miR-29b, miR-30d,
      miR-34a, miR-93, miR-126, miR-146a, miR-148, miR-150, miR-155, and miR-223,
      significantly changed across the diabetes spectrum, and were associated with
      measures of pancreatic islet beta cell function and glycemic control, among
      others. Notably, SFRP4 was the only studied cytokine that was significantly
      associated with obesity, prediabetes, and T2D, which underscores the important
      role of this molecule during disease development and progression. Our data
      suggest that changes in circulating miRNAs and cytokines may have clinical
      utility as biomarkers of prediabetes.

PMID- 27869910
TI  - The methanol-ethyl acetate partitioned fraction from Chinese olive fruits
      inhibits cancer cell proliferation and tumor growth by promoting apoptosis
      through the suppression of the NF-kappaB signaling pathway.
AB  - Chinese olives (Canarium album L.) have historically been used for medicinal
      purposes rather than commercially for oil. In this report, we reveal that the
      methanol-ethyl acetate partitioned fraction from Chinese olive fruits (MEO), of
      which ellagic acid accounted for 12%, exhibited profound anti-proliferative
      activities in the human colon cancer cell line, HCT116. Additionally, oral
      administration of MEO remarkably inhibited the tumor growth of subcutaneously
      implanted CT26 cells, a mouse colon carcinoma cell line, in BALB/c mice.
      Treatment with MEO induced a significant increase in the percentage of apoptotic
      cells and resulted in poly(ADP-ribose) polymerase (PARP) cleavage, suggesting
      that MEO inhibits cancer cell proliferation by promoting apoptosis. Our study
      also showed that MEO exerted the most potent effect on the inhibition of NF
      kappaB-mediated signaling among the partitioned fractions from Chinese olives.
      This process employed the use of reporter-based bio-platforms that are capable of
      detecting the activation of NF-kappaB. In addition, phosphorylation of NF-kappaB
      signaling-associated proteins, IKKalpha/beta, IkappaBalpha, and p65, was reduced
      in MEO-incubated cancer cells, indicating that MEO suppresses NF-kappaB
      activation. Moreover, MEO treatment significantly suppressed lipopolysaccharide
      (LPS)-induced cancer cell proliferation, demonstrating that MEO promotes cancer
      cell apoptosis through the inhibition of the NF-kappaB signaling pathway. In
      summary, our findings demonstrate that the methanol-ethyl acetate partitioned
      fraction from Chinese olive fruits inhibits cancer cell proliferation and tumor
      growth by promoting apoptosis through the suppression of NF-kappaB signaling.
      Therefore, the Chinese olive fruit has promising potential in cancer treatment.

PMID- 27869911
TI  - Controlled production of sub-millimeter liquid core hydrogel capsules for
      parallelized 3D cell culture.
AB  - Liquid core capsules having a hydrogel membrane are becoming a versatile tool for
      three-dimensional culture of micro-organisms and mammalian cells. Making sub
      millimeter capsules at a high rate, via the breakup of a compound jet in air,
      opens the way to high-throughput screening applications. However, control of the
      capsule size monodispersity, especially required for quantitative bioassays, was
      still lacking. Here, we report how the understanding of the underlying
      hydrodynamic instabilities that occur during the process can lead to calibrated
      core-shell bioreactors. The requirements are: i) damping the shear layer
      instability that develops inside the injector arising from the co-annular flow
      configuration of liquid phases having contrasting viscoelastic properties; ii)
      controlling the capillary instability of the compound jet by superposing a
      harmonic perturbation onto the shell flow; iii) avoiding coalescence of drops
      during jet fragmentation as well as during drop flight towards the gelling bath;
      iv) ensuring proper engulfment of the compound drops into the gelling bath for
      building a closed hydrogel shell. We end up with the creation of numerous
      identical compartments in which cells are able to form multicellular aggregates,
      namely spheroids. In addition, we implement an intermediate composite hydrogel
      layer, composed of alginate and collagen, allowing cell adhesion and thus the
      formation of epithelia or monolayers of cells.

PMID- 27869912
TI  - Correction: In solution SERS sensing using mesoporous silica-coated gold
      nanorods.
AB  - Correction for 'In solution SERS sensing using mesoporous silica-coated gold
      nanorods' by Zhe Gao, et al., Analyst, 2016, 141, 5088-5095.

PMID- 27869913
TI  - ?

PMID- 27869915
TI  - Changes in the paradigm of clinical and therapeutic management of Chagas'
      disease: progress and perspectives in the pursuit of comprehensive health.

PMID- 27869916
TI  - The invisible magnitude of violence against women.

PMID- 27869917
TI  - [Method for projecting indicators for the goals of the Strategic Action Plan for
      Tackling Chronic Non-Communicable Diseases in Brazil according to Capitals and
      the Federal District].
AB  - OBJECTIVE: to present the indicators' projection method of the Strategic Action
      Plan for Tackling Chronic Non-Communicable Diseases (NCDs) in Brazilian State
      capitals and the Federal District, 2012-2022. METHODS: simple linear regression
      model was used to calculate the indicators' projections with data from the
      Surveillance System of Risk and Protective Factors for Chronic Diseases by
      Telephone Survey (Vigitel). RESULTS: in most of the capitals, there was an
      increase in the prevalence of obesity (annual change: 0.36%;1.29%), overweight
      (annual change: 1.11%;2.00%), recommended (annual change: 1.45%;2.66%) and
      regular (annual change: 0.45%;1.46%) consumption of fruits and vegetables;
      smoking presented a decreasing trend (annual change: -1.34%;-0.20%); whereas
      physical inactivity, heavy drinking and mammography and Pap smears examinations
      were stable. CONCLUSION: most of the goals are possible; however, effective
      actions are necessary, especially for tackling overweight and heavy drinking.

PMID- 27869914
TI  - [Brazilian Consensus on Chagas Disease, 2015].
AB  - Chagas disease is a neglected chronic condition that presents high morbidity and
      mortality burden, with considerable psychological, social, and economic impact.
      The disease represents a significant public health issue in Brazil, with
      different regional patterns. This document presents the evidence that resulted in
      the Brazilian Consensus on Chagas Disease. The objective was to review and
      standardize strategies for diagnosis, treatment, prevention, and control of
      Chagas disease in the country, based on the available scientific evidence. The
      consensus is based on collaboration and contribution of renowned Brazilian
      experts with vast knowledge and experience on various aspects of the disease. It
      is the result of close collaboration between the Brazilian Society of Tropical
      Medicine and the Ministry of Health. This document shall strengthen the
      development of integrated control measures against Chagas disease in the country,
      focusing on epidemiology, management, comprehensive care (including families and
      communities), communication, information, education, and research.

PMID- 27869918
TI  - Spatial and temporal analysis of Aids cases in Brazil, 1996-2011: increased risk
      areas over time.
AB  - OBJECTIVE: to identify areas with greater risk of AIDS transmission in Brazil.
      METHODS: this is an ecological study involving georeference of AIDS cases
      incidence, prevalence and density in Brazilian municipalities using the Kernel
      method for the periods 1996-1999, 2000-2003, 2004-2007 and 2008-2011. RESULTS:
      633,512 AIDS cases were reported between 1996-2011; between 2008-2011, there was
      increased risk of AIDS transmission in Recife-Joao Pessoa region, the emergence
      of areas with average density in the regions of Belem, Sao Luis, Maceio, Aracaju
      and Salvador, and a decline in the intensity of risk in Sao Paulo, Campinas and
      Ribeirao Preto; prevalence rates were most concentrated in the Southeast, South
      and Midwest regions of the country. CONCLUSION: overall, AIDS incidence in Brazil
      showed successive increases in the periods analyzed; case prevalence indicates
      spatial clusters, with high concentrations in the Southeast, South and Midwest
      regions.

PMID- 27869919
TI  - Aids mortality trends according to sociodemographic characteristics in Rio Grande
      do Sul State and Porto Alegre City, Brazil: 2000-2011.
AB  - OBJECTIVE: to analyze AIDS mortality trends in Rio Grande do Sul State (RS) and
      Porto Alegre City (POA) according to sociodemographic characteristics in the
      period 2000-2011. METHODS: this was an ecological time series study of AIDS
      mortality rates; Prais-Winsten regression model was used. RESULTS: the
      standardized mortality AIDS rate showed a stationary trend in RS (1.3%; 95%CI: 
      0..;6.7) and in POA (-0.3%; 95%CI: -5.1;3.9); there was an increasing trend in
      the following categories: women in RS (4.1%; 95%CI: 3.0; 5.3) and in POA (2.7%;
      95%CI: 1.8; 3.5), people with brown skin color in RS (4.5%; 95%CI: 1.9; 7.2) and
      in POA (4.6%; 95%CI: 1.5; 7.9), the 40-49 age group in RS (4.0%; 95%CI: 1.3;
      6.7), the 50-59 age group in RS (5.8%; 95%CI: 1.9; 9.9) and in POA (6.0%; 95%CI:
      2.1; 9.9), and the >60 age group in RS (4.0%; 95%CI: 1.1; 6.9). CONCLUSION: AIDS
      mortality increased among women, individuals with brown skin color and older age
      groups in RS and POA.

PMID- 27869920
TI  - [Description of duplicate records held on the Notifiable Diseases Information
      System, Brazil, 2008-2009].
AB  - OBJECTIVE: to describe the proportion of duplicate records held on the Brazilian
      Notifiable Diseases Information System, 2008-2009. METHODS: identification of
      duplicate records of dengue, leprosy, visceral leishmaniasis and cutaneous
      leishmaniasis, meningitis and tuberculosis was conducted using Reclink III(r);
      the proportion of duplicate records was calculated by geographical region, state
      and municipal population size categories. RESULTS: visceral leishmaniasis (VL)
      and meningitis had higher proportions of duplicate notification (5.3% and 3.6%,
      respectively) whilst leprosy had the lowest (0.7%); the states with highest
      repetitions were Rio Grande do Norte (VL 6.8% and leprosy 5.1%), Rio de Janeiro
      (tuberculosis 2.5% and meningitis 4.9%) and Goias (dengue 2.0% and meningitis
      7.2%). CONCLUSION: the Northeast region had the highest proportion of duplicate
      records for four of the six diseases analyzed; with the exception of dengue,
      percentage repetition was lower in municipalities with larger population size.

PMID- 27869921
TI  - 2014 FIFA World Cup Brazil: active surveillance and profile of health care in the
      host city of Fortaleza, Ceara, Brazil.
AB  - OBJECTIVE: to describe the real-time active surveillance strategy and the profile
      of health care provided during the 20th FIFA World Cup Brazil 2014 (FWCB), in the
      host city of Fortaleza, Ceara, Brazil. METHODS: this was a descriptive study with
      data collected from medical records during the FWCB, between June 8 and July 13,
      2014, in pre-selected health care units. RESULTS: there were 2,570 medical
      assistances related to the FWCB; 56% of the patients were male, 35% were between
      20 and 29 years old; 68% were clinical care, and 64% of the individuals were
      fans/spectators; 94% of the patients were discharged, 3% were referred, 3% were
      hospitalized and 0.2% died; the advanced medical units were responsible for 79%
      of the assistances, mainly on game days. CONCLUSION: no public health event of
      great importance was identified; the active surveillance strategy enabled the
      monitoring of health situation of those individuals involved in the event.

PMID- 27869922
TI  - [Healthcare profile of rabies pre-exposure prophylaxis in the state of Rio Grande
      do Sul, Brazil, 2007-2014].
AB  - OBJECTIVE: to describe the profile of healthcare provision regarding rabies pre
      exposure prophylaxis (RPrEP) in the state of Rio Grande do Sul, Brazil, as
      compared with the Technical Standards for Rabies Prophylaxis in Humans. METHODS:
      this was a descriptive study using Notifiable Disease Information System data on
      anti-rabies healthcare provided between 2007 and 2014. RESULTS: only 2.4% of anti
      rabies healthcare related to RPrEP (5,721/239,245), 42.5% of these were
      veterinary, biology and zootechnics students and 10.3% were professionals from
      the same areas; individuals aged 20 to 64 accounted for 71.8% of the total number
      of people vaccinated and the frequency of this form of prophylaxis was
      53.5/100,000 inhabitants for the state as a whole, varying between 13.1 to
      185.1/100,000 inhabitants in the state's different health districts. CONCLUSION:
      RPrEP frequency was found to be low, suggesting that this rabies prevention tool
      has been neglected, leaving a large number of people at occupational risk.

PMID- 27869923
TI  - Cross-sectional study on case fatality rate due to hantavirus infection in Goias
      State, Brazil, 2007-2013.
AB  - OBJECTIVE: to describe the epidemiological and clinical profile of hantavirus
      infection and to analyze factors associated with case-fatality in Goias, Brazil.
      METHODS: this was a cross-sectional study on case fatality due to hantavirus
      infection from 2007 to 2013 using data from the Notifiable Diseases Information
      System (SINAN) for Goias State. Logistic regression analysis was performed to
      estimate odds ratios (OR) with 95% confidence intervals (95%CI). RESULTS: 1,171
      suspected cases were reported, of which 73 (6.2%) were confirmed. Among the
      confirmed cases, greater frequency was found among males (n=50), fever was the
      most common symptom (n=70), and there was a high proportion of hospitalization
      (n=68). The case-fatality rate was 57.5% . The following factors were associated
      with death: acute respiratory failure (ARF) (OR=3.6; 95%CI 1.2;10.6),
      hemoconcentration (OR=3.3; 95%CI 1.1;7.9) and not using a mechanical ventilator
      (OR=3.4; 95%CI 1.3;9.1). After adjustment, the ARF was still associated with
      death (OR=3.4; 95%CI 1.0;11.6). CONCLUSION: the case-fatality rate was high,
      primarily associated with respiratory failure.

PMID- 27869924
TI  - Yellow fever outbreaks in Sao Paulo State, Brazil, 2000-2010.
AB  - OBJECTIVE: to describe yellow fever occurrence in the state of Sao Paulo, Brazil,
      in the period 2000-2010. METHODS: this was a descriptive study using data
      regarding human cases, epizootics in non-human primates and virus vector
      isolation in Sao Paulo State, between 2000 and 2010. RESULTS: three sylvatic
      yellow fever outbreaks were registered in the state with 32 human cases and 15
      deaths; the cases occurred in unvaccinated individuals exposed to the sylvatic
      form of transmission; epizootics was confirmed before the virus began circulating
      in humans in the region of Sao Jose do Rio Preto and the virus was isolated twice
      in vectors. CONCLUSION: three sylvatic yellow fever outbreaks occurred in the
      state between 2000 and 2010, two of them in a transition area and the other in an
      area considered to be unaffected; vaccination and maintaining immunization
      coverage are necessary for preventing the disease.

PMID- 27869925
TI  - Time trends in mortality from intestinal infectious diseases among children under
      five years old, in Sao Paulo State, Brazil, 2000-2012.
AB  - OBJECTIVE: to analyze time trends in mortality owing to intestinal infectious
      diseases (IID) among children under five years of age in Sao Paulo State and its
      Regional Health Care Networks (RRAS), from 2000 to 2012. METHODS: this was a time
      series study of deaths having IID as their underlying, antecedent or contributory
      cause, using Mortality Information System data. RESULTS: there were 2,886 deaths
      from IID in the state; the IID mortality rate went down by 10.5% per year (95%CI
      4.8;15.8%); there was a significant decrease in the mortality rate in 13 of the
      17 RRAS, with annual decrease in the range 16.6% - 8.3%. CONCLUSION: The IID
      mortality rate went down significantly in most RRAS, at different speeds,
      possibly reflecting inequalities in socio-economic conditions and health care
      network organization.

PMID- 27869926
TI  - [Delay in tuberculosis diagnosis in adults in a city of Sao Paulo State, Brazil,
      in 2009: a cross-sectional study].
AB  - OBJECTIVE: to evaluate patient and health service characteristics associated with
      tuberculosis (TB) diagnosis delay. METHODS: this was a cross-sectional study
      conducted in Sao Jose do Rio Preto-SP in 2009; the 'entry point' and 'access to
      diagnosis' dimensions of the Primary Care Assessment Tool (PCAT) were selected to
      analyze patient and HS delay. RESULTS: 99 TB patients were included in the study;
      the median time related to patient and HS delay was 15 days; delay in seeking
      services was lower among smokers (PR= 0.71; 95%CI 0.54;0.94) and alcohol users
      (PR=0.75; 95%CI 0.57;0.99); TB diagnosis delay was related to not being able to
      get a medical appointment on the same day (PR=1.63; 95%CI 1.22;2.18), TB not
      being suspected (PR=2.07; 95%CI 1.18;3.62) and seeking care in health services
      four times or more (PR=2.34; 95%CI 1.55;3.53). CONCLUSION: delay in seeking care
      was lower among smokers and alcohol users; shortcomings in access to diagnosis
      characterized health services delay.

PMID- 27869927
TI  - [Evaluation of the organization of health services as a strategy for the
      prevention and control of visceral leishmaniasis].
AB  - OBJECTIVE: to evaluate the organization of health services as a strategy for the
      prevention and control of visceral leishmaniasis (VL) in Ribeirao das Neves,
      Minas Gerais, Brazil, from 2010 to 2012. METHODS: this was a case study
      evaluation of the degree of implementation of a strategy for the integration of
      health care services, control of zoonosis and epidemiological surveillance; it
      consisted of observing the work process, interviewing health professionals and
      analysing secondary data from information systems. RESULTS: implementation was
      partially adequate (84%); in terms of structure, the human resources component
      had the worst evaluation (64%) whilst in terms of work process, evaluation was
      80% for reorganization of care and 77% for surveillance; in the period 2010-2012
      there was a 20% increase in reported cases of VL and a 20% reduction in the time
      interval between reporting a case and starting treatment. CONCLUSION: the
      strategy contributed to the improvement of the organization of VL prevention and
      control actions.

PMID- 27869928
TI  - [Characterization of printed educational materials about schistosomiasis used in
      health education in endemic areas in Brazil].
AB  - OBJECTIVE: to characterize printed educational materials about schistosomiasis
      produced at federal, state and municipal levels in Brazil. METHODS: the
      educational materials were characterized considering the following categories:
      'format', 'parasite and intermediate host', 'definitive host (ill)' and
      'disease'. RESULTS: 60 materials were assessed, three had no information about
      risk activities and 41 indicated more than one popular name for the disease, thus
      allowing greater reach among the target audience in diverse endemic areas; the
      biological cycle was missing or incorrect in 53 materials; the intermediate host
      (snail) was incorrectly illustrated, with use of stereotyped images in 39 and no
      image in one material; diagnosis was mentioned in 36 materials. CONCLUSION: the
      printed educational materials assessed had incorrect content which may compromise
      health education efforts; little attention was paid to schistosomiasis diagnosis.

PMID- 27869929
TI  - [Municipal Monitoring Panel: Bases for building a health service management
      tool].
AB  - OBJECTIVE: To describe and critically analyze the steps taken and the technical
      references used to build the Sao Paulo City Health Department Monitoring Panel,
      highlighting its potentials and limits for the decision-making process. METHODS:
      This was a qualitative study based on analysis of official documents and semi
      structured interviews with key informants. The data was submitted to thematic
      analysis aimed at understanding the technical choices and paths taken to build
      the Panel. RESULTS: The Panel provides numerical and graphical reports applying
      four statistical analysis models, thus facilitating access to information and
      data analysis by different management levels. CONCLUSIONS: The Panel provides
      analysis options for different management levels, thus strengthening
      decentralized decisions. It is a streamlined and appropriate monitoring strategy
      as well as being able to be used in different management contexts and territory
      sizes.

PMID- 27869930
TI  - [Assessment of Service to verify the cause of death implementation in Pernambuco
      State, Brazil, 2012: multiple case study].
AB  - OBJECTIVE: to evaluate the implementation of Death Verification Services in
      Pernambuco State, Brazil, in 2012. METHODS: this was an implementation analysis
      evaluation study; we constructed a logical framework and judgement matrix were
      prepared; primary data (direct observation and interviews) and secondary data
      were used; assessment of the level of Death Verification Services implementation
      was based on outcome-related structure and process indicators which were compared
      with the logical framework. RESULTS: the Recife and Caruaru Death Verification
      Services were considered to have achieved Advanced Partial Implementation,
      consistent with the outcome indicators measured, reaching 89.0% and 82.0% of the
      expected values, respectively; the Information Collection and
      Nosological/Aetiological Diagnosis components were considered to Fully
      Implemented at the Recife and Caruaru Death Verification Services; whilst the
      Education and Research component was only considered to be Fully Implemented at
      the Recife Death Verification Services. CONCLUSION: level of implementation was
      similar at both services; the higher level of the Education and Research
      component at the Recife Death Verification Services reveals the importance of
      technical and academic cooperation.

PMID- 27869931
TI  - [Descriptive study of the profiles of victims of firearm projectile injuries and
      healthcare costs in a hospital in the Viva Sentinela Network].
AB  - OBJECTIVE: to describe the profile of victims with injuries caused by firearm
      projectiles and the cost of treatment at a referral hospital in Midwestern Brazil
      belonging to the Viva Sentinela Network. METHODS: a descriptive study with
      convenience samplie was conducted from January to March 2013; data sources were
      interviews, patients' medical records, and the hospital statistics department.
      RESULTS: the 150 victims who participated were predominantly male (94.7%), young
      (67.3%), and drug/alcohol users (80.0%); the main reason of these incidents was
      drug trafficking/drug debt (45.3%); average health care costs were R$1,291.93 per
      case. CONCLUSION: the majority of victims were young male users of alcohol/drugs,
      and involvement with trafficking was the most frequent reason for victimization;
      average health care costs for these patients were high.

PMID- 27869933
TI  - No magic bullet: citizenship and social participation in the control of Aedes
      aegypti.

PMID- 27869932
TI  - Severe maternal morbidity identified in the Hospital Information System of the
      Brazilian National Health System in Parana State, Brazil, 2010.
AB  - OBJECTIVE: to describe near miss maternal morbidity among women living in Parana
      State, Brazil, in 2010. METHODS: this was a descriptive study using Brazilian
      National Hospital Information System (SIH/SUS) data on all hospital admissions
      with primary diagnosis falling under Chapter XV of the International Statistical
      Classification of Diseases and Related Health Problems 10th Revision and/or with
      records of obstetric procedures indicative of near misses; three criteria were
      used to define severe maternal morbidity. RESULTS: 4,890 admissions owing to near
      miss were identified, with a rate of 52.9 hospitalizations per 1,000 births, a
      rate of 69.8/1,000 among women aged 35-39 and a rate of 356.6/1,000 among women
      aged 44-49; the leading causes of hospitalization were preeclampsia (28.2%),
      haemorrhage (23.7%) and immune system dysfunction (14.0%). CONCLUSION: the
      results indicate the need to pay greater attention to women aged 35 and over
      since they had higher rates of near miss.

PMID- 27869934
TI  - Breastfeeding and risk of dental caries.

PMID- 27869936
TI  - [Adherence to medication among hypertensive patients participating in the
      Medicine at Home Program].
AB  - OBJECTIVE: to analyze adherence to medication and associated among factors
      hypertensive individuals taking part in the Medicine at Home Programme. METHODS:
      this was a cross-sectional study using a questionnaire administered to patients
      with full access to medication participating in the Sao Paulo City Health
      Department's Medicine at Home Programme; treatment adherence was analyzed
      according to sociodemographic and behavioral characteristics using Poisson
      regression. RESULTS: 106 patients with arterial hypertension and with full access
      to medication were interviewed and 80.2% had high adherence; there were no
      significant differences (p>0.05) between adhering and non-adhering participants
      with regard to sociodemographic, behavioral or clinical characteristics.
      CONCLUSION: with adequate provision of health care and full access to medicine,
      sociodemographic, behavioral and clinical factors did not influence adherence to
      medicine indicating that health service organization and health policies play a
      fundamental role in controlling hypertension.

PMID- 27869935
TI  - Method for estimating infant mortality and low birth weight indicators for
      Brazilian municipalities, 2012.
AB  - OBJECTIVE: to present a method for estimating low birth weight (LBW) prevalence
      and infant mortality rate (IMR) indicators for Brazilian municipalities, so as to
      incorporate considerations with regard to sampling fluctuation. METHODS: binomial
      and Poisson distributions were used to estimate 95% confidence intervals (95%CI);
      when the number of infant deaths was zero, the upper limit of the 95%CI was
      estimated by the cross-multiplication method; indicators were estimated for the
      year 2012 for demonstration purposes. RESULTS: a slight increase in LBW and a
      decrease in IMR were detected as municipality population size increased; LBW
      estimates were more accurate than those for IMR; single-year estimates showed
      large width 95%CI in small municipalities and low reliability. CONCLUSION: an
      electronic spreadsheet was developed which will allow service managers to
      estimate the precision of these indicators for their municipalities.

PMID- 27869937
TI  - Factors associated to toxoplasmosis-related knowledge among pregnant women
      attending public health services in the municipality of Niteroi, Rio de Janeiro,
      Brazil, 2013-2015.
AB  - OBJECTIVE: to analyze the factors associated to toxoplasmosis-related knowledge
      among pregnant women attending public health services in the municipality of
      Niteroi, Rio de Janeiro, Brazil. METHODS: this is a cross-sectional study
      conducted with pregnant women assisted in eight health care units; data was
      collected using a standardized questionnaire, from April 2013 to February 2015.
      RESULTS: among the 405 pregnant women interviewed, 173 (42.7%) knew about
      toxoplasmosis and, of those, 24.3% knew about it through friends; the proportion
      of pregnant women with toxoplasmosis-related knowledge increased with age
      (p<0.001), education level (p<0.001) and the number of pregnancies (p=0.031); the
      history of abortion was also associated with toxoplasmosis-related knowledge
      (p=0.019). CONCLUSION: the variables 'age', 'education level', 'number of
      pregnancies' and 'abortion history' were important factors for toxoplasmosis
      related knowledge among pregnant women assisted in the public health care sector
      of Niteroi.

PMID- 27869939
TI  - [ERRATA].
AB  - [This corrects the article doi: 10.5123/S1679-49742014000400021] [This corrects
      the article doi: 10.5123/S1679-49742016000100009] [This corrects the article doi:
      10.5123/S1679-49742016000200015].

PMID- 27869938
TI  - Outcomes in health economic evaluation studies.

PMID- 27869940
TI  - ?

PMID- 27869941
TI  - Monitoring respiratory virus infection in the metropolitan area of Belo
      Horizonte, Brazil, 2011-2013.
AB  - OBJECTIVE: to analyze the circulation of respiratory viruses in people living in
      the metropolitan area of Belo Horizonte, Brazil, and hospitalized in Belo
      Horizonte from 2011 to 2013. METHODS: this is a descriptive study of 5,158
      patients with Severe Acute Respiratory Syndrome; a comparison was made between
      the characteristics of confirmed cases and those of discarded cases or cases
      without swab samples. RESULTS: Influenza A virus accounted for half the isolated
      viruses, especially subtype A(H1N1)pdm09 among patients aged 20-59 years old, and
      subtype A(H3N2) in those aged 60 or over; the most frequently identified
      respiratory virus among children under five years old was respiratory syncytial
      virus (65.6%), followed by influenza A virus (21.2%); influenza virus circulated
      in all seasons of the year and its periods of greatest incidence were
      interspersed with those of higher Respiratory Syncytial Virus activity.
      CONCLUSION: monitoring respiratory viruses contributes to knowledge about periods
      of virus circulation and the adoption of specific control measures.

PMID- 27869942
TI  - [Prevalence and worm burden of Schistosomiasis mansoni before and after
      collective treatment in Jaboatao dos Guararapes, Pernambuco, Brazil].
AB  - OBJECTIVE: to evaluate the effectiveness of collective treatment for
      Schistosomiasis mansoni in two endemic localities in Jaboatao dos Guararapes-PE.
      METHODS: we described the prevalence of Schistosomiasis mansoni and the average
      parasite load before and after collective treatment in the period 2011-2013; data
      from the Schistosomiasis mansoni Information System and completion of sample
      surveys reports were used. RESULTS: there is a reduction in 8.9% positivity rate
      to 2.3% in Barra de Jangada and from 15.7% to 3.5% in Novo Horizonte; there was a
      decrease of the parasitic load average in Novo Horizonte (67.0 to 52.7 eggs/gram
      of feces) and increase in Barra de Jangada (23.8 to 91.7 eggs/gram of feces).
      CONCLUSION: the collective treatment contributed to reducing the rate of
      positivity in endemic areas.

PMID- 27869943
TI  - Use of generic drugs in Sao Paulo city, Brazil, in 2003: a population-based
      study.
AB  - OBJECTIVE: to analyze the use and perception of generic drugs by people with
      diabetes and hypertension in Sao Paulo City, Brazil, considering the Brazilian
      Generic Drug Policy. METHODS: this was a cross-sectional study using data from a
      household health survey (ISA-Capital) in 2003; analysis was performed on
      knowledge regarding generic drugs and on the association between their use and
      sociodemographic and socio-economic characteristics. RESULTS: 603 people with
      hypertension and diabetes were included in the study, low use of generic drugs
      was found (33.3% and 26.3, respectively) and low cost was the major reported
      advantage of generic drugs (71.0% and 71.1%, respectively); there was no
      statistically significant difference between the use of generic medication and
      age, sex or schooling. CONCLUSION: low cost and there being no difference between
      generic drug use and education level strengthen the importance of generic drugs
      for promoting equity and universal access to medication.

PMID- 27869944
TI  - Evaluation of drug prescription quality indicators in a primary health care
      facility with different models of health care.
AB  - OBJECTIVE: to describe drug prescription indicators in a primary health care
      facility with different models of health care. METHODS: this was a descriptive
      study using secondary data of prescriptions with regard to quality indicators in
      a health facility that has three health care models: Outpatient Medical Care
      (OMC), Primary Health Care Unit (PHU) and Family Health Strategy (FHS) in Vila
      Nova Jaguare OMC/PHU in Sao Paulo-SP, Brazil, from July to October 2011. RESULTS:
      16,720 prescriptions were studied; the proportion of drugs provided through the
      Municipal List of Essential Drugs (Remume) was higher for FHS prescriptions
      (98.9%), compared to PHU (95.6%) and OMC (95.7%); similarly, both the use of the
      generic name of the drugs and the proportion of drugs provided was higher among
      ESF prescriptions (98.9% and 96.1%, respectively), compared with PHU (94.4 % and
      92.9%) and OMC (94.0% and 92.7 %). CONCLUSION: all the prescription indicators
      show better results for FHS.

PMID- 27869946
TI  - Skin-to-skin contact at birth: a challenge for promoting breastfeeding in a "Baby
      Friendly" public maternity hospital in Northeast Brazil.
AB  - OBJECTIVE: to identify prevalence of compliance with the fourth step of the Baby
      Friendly Hospital Initiative - to put the babies in skin-to-skin contact with
      their mothers immediately after birth for at least half an hour - in a public
      hospital in Northeast Brazil. METHODS: this was a cross-sectional study using
      data from interviews with mothers who had recently given birth during a typical
      week in 2014. RESULTS: 107 mothers were interviewed; 9.3% had completed the
      fourth step properly; the fourth step was negatively associated to cesarean
      section (p<0.01), and adequacy was not associated with receiving guidance on
      breastfeeding during the prenatal period or with breastfeeding in the first hour
      of life. CONCLUSION: low compliance with the fourth step is cause for concern,
      especially because this is a Baby-Friendly Hospital; cesarean section was
      detrimental to infant skin-to-skin contact with their mothers immediately after
      birth.

PMID- 27869945
TI  - [Assessment of the adequacy of prenatal care according to family income in
      Aracaju, Sergipe State, Brazil, 2011].
AB  - OBJECTIVE: to assess the adequacy of prenatal care offered to pregnant health
      service users in Aracaju, Sergipe State, Brazil, according to family income.
      METHODS: this was a cross-sectional study with 322 women living in the city of
      Aracaju whose children were born in November and December 2011; data were
      collected using questionnaires, including number of consultations, technical and
      laboratory procedures recommended by the Brazilian Ministry of Health (MoH);
      adequacy of prenatal care was assessed according to MoH criteria; chi-square test
      was used to compare proportions between categorical variables. RESULTS: prenatal
      care was considered inadequate for 89.1% of women, with no statistical difference
      for inadequacy of prenatal care according to family income (p=0.323). CONCLUSION:
      low adequacy of prenatal care was found when applying MoH parameters, regardless
      of pregnant women's family income.

PMID- 27869947
TI  - [Adolescent health risk behaviors and Family Health Strategy educational
      activities in Cuiaba, Mato Grosso State, Brazil, 2011].
AB  - OBJECTIVE: to analyze health risk behaviors in adolescents and Family Health
      Strategy (FHS) educational activities in Cuiaba, Mato Grosso State, Brazil.
      METHODS: a cross-sectional study was conducted using data from a survey with
      adolescents registered with FHS in 2011/2012; Poisson regression was used to
      estimate prevalence ratios (PR) and 95% confidence interval (CI95%). RESULTS:
      there was low participation in educational activities on alcohol (23%), food
      (10%) and physical activity (9%); insufficient physical activity was higher in
      girls (PR=0.76 - 95%CI 0.68;0.85), alcohol consumption was associated with the 15
      19 age range (PR=1.48 - 95%CI 1.29;1.71) and low fruit and vegetable intake was
      associated with income of <=2 minimum wages (PR=1.17 - 95%CI 1.02;1.33).
      CONCLUSION: there was no significant association between adolescent risk
      behaviors and their participation in FHS educational activities.

PMID- 27869948
TI  - [Risk factors for cardiovascular disease in prison institution staff: a cross
      sectional study].
AB  - OBJECTIVE: to analyze risk factors for cardiovascular disease in prison
      institution staff. METHODS: this was a cross-sectional study with a sample of 127
      staff of both sexes; prevalence ratios (PR) were estimated adjusted for age and
      education, as were the respective 95% confidence intervals (95%CI). RESULTS:
      higher proportions of waist circumference ratios were found above the recommended
      values (58.1%) and the accumulation of two risk factors for females (33.8%);
      among males there was higher prevalence of abnormal glucose levels (PR=10.73 -
      95%CI 1.31;87.92) and blood pressure (PR=2.63 - 95%CI 1.31;6.50). CONCLUSION: the
      risk factors for cardiovascular disease found among staff in this study were
      waist circumference, glucose levels and blood pressure above the recommended
      values; these health risks can to be addressed through health promotion and
      disease prevention measures, as well as effective attention to those who are
      already sick.

PMID- 27869949
TI  - [Cervical cancer mortality in the state of Rio Grande do Norte, Brazil, 1996
      2010: time trends and projections up to 2030].
AB  - OBJECTIVE: to analyze cervical cancer mortality trends in the state of Rio Grande
      do Norte and its health micro-regions from 1996 to 2010, as well as to make
      projections for five-year periods from 2011 to 2030. METHODS: this was an
      ecological time series study; negative binomial regression was used to analyze
      trends and projections. RESULTS: rates above 5.0 deaths per 100,000 women were
      observed in all the micro-regions, with a stationary trend in the state as a
      whole and an upward trend in the micro-regions with the worst socioeconomic
      conditions; projections indicated reduction in mortality rates in the state, from
      5.95/100,000 women (2006-2010) to 3.67 (2026-2030), although a 22% increase in
      the absolute number of deaths is expected. CONCLUSION: although a reduction in
      mortality rates is projected, they continue to be high, indicating the need for
      review and strengthening of the state's cervical cancer control program.

PMID- 27869950
TI  - [Time-trend analysis of homicide and traffic accident mortality in Foz do Iguacu,
      Brazil, 2000-2010].
AB  - OBJECTIVE: to perform time-trend analysis of homicide and land transport accident
      (LTA) mortality in Foz do Iguacu city, Brazil, 2000-2010. METHODS: this was a
      time series study, using Mortality Information System data on people resident in
      the city; death rates by sex were calculated and standardized by age; Prais
      Winsten regression was used. RESULTS: 3,459 deaths were recorded in the period
      (881 owing to LTA and 2,578 owing to homicides); the highest homicide mortality
      rate was 104.6 per 100,000 inhabitants in 2006, whilst for LTA it was 35.9 per
      100,000 inhabitants in 2010; LTA and homicide mortality rates showed stability;
      higher mortality rates were found in the 20-39 age group. CONCLUSION: the
      maintenance high homicide and LTA mortality rates point to the need to pay
      greater attention to these problems.

PMID- 27869951
TI  - [Epidemiological characteristics of violence against women in the Federal
      District, Brazil, 2009-2012].
AB  - OBJECTIVE: to describe the epidemiological characteristics of cases of violence
      against women reported in the Federal District, Brazil, 2009-2012. METHODS: this
      was a descriptive study of cases of violence against women aged 18- 59 registered
      on the National Notifiable Diseases System (Sinan). RESULTS: 1,924 cases of
      violence against women were registered, the perpetrators of which were identified
      as unknown (25.7%) or spouses (19.0%) of the victims; violence mainly occurred
      against women of brown skin color (25.0%) and in the domestic environment
      (38.5%); regarding violence type, physical violence (46.8%) by force (48.0%)
      stood out, whereby the genitals (15.7%) and the head (12.9%) were the most
      affected regions. CONCLUSION: physical violence in domestic environments by
      unknown aggressors was the main type of violence among the reported cases;
      shortcomings were identified in recording reported cases, showing the need to
      improve system quality and train health workers involved.

PMID- 27869953
TI  - Profile of work-related road traffic accident victims recorded by sentinel health
      units in Pernambuco, Brazil, 2012-2014.
AB  - OBJECTIVE: to describe the profile of work-related road traffic accident (RTA)
      victims, reported by Road Traffic Accident Information Sentinel Units in the
      state of Pernambuco, Brazil, from 2012-2014. METHODS: descriptive study of fatal
      and non-fatal work-related road traffic accident victims, reported by 21 RTA
      Information Sentinel Units in Pernambuco. RESULTS: 87.8% of the 10,691 cases
      reported occurred among males; 69.0% of all records were related to the 20-39 age
      group; the sectors with most injured workers were Transport (24.4%) and Trade
      (21.3%); most of the victims were drivers (82.0%) and motorcycles were the most
      frequent vehicle at the time of the accident (77.0%). CONCLUSION: victims were
      predominantly young male motorcyclists; findings may serve to inform
      intersectoral actions to prevent work-related RTAs, appropriate to the profile of
      the victims.

PMID- 27869952
TI  - [Poison-related hospitalizations of children aged 0-14 at a teaching hospital in
      Southern Brazil, 2006-2011].
AB  - OBJECTIVE: to describe the profile of poisoning leading to children's
      hospitalizations, as registered at the Maringa Regional University Hospital
      Poisoning Control Center in the period 2006 to 2011. METHODS: this was a
      descriptive epidemiological study using secondary data from Intoxication Incident
      Report Forms, involving poisoned children aged between 0 and 14 years,
      hospitalized for at least 12 hours. RESULTS: 694 hospitalizations due to
      poisoning were registered, with medication poisoning accounting for 42.4% of
      cases; the 1-4 age group was the most affected (66.7%); males accounted for a
      higher number of hospital admissions in all age groups; most poisoning cases
      occurred in the morning (55.6%). CONCLUSION: medication was the main cause of
      poisoning; younger children and males were predominant among hospitalized
      victims.

PMID- 27869954
TI  - [Reporting of work-related mental disorders among workers in Bahia: a descriptive
      study, 2007-2012].
AB  - OBJECTIVE: to describe characteristics of work-related mental disorder (WRMD)
      cases in the State of Bahia, Brazil, 2007-2012. METHODS: this was a descriptive
      study using Bahia Surveillance and Health Protection Superintendents Office data
      kept on the Notifiable Diseases Information System (Sinan). RESULTS: 211 cases of
      WRMD were reported, 97.0% in the Worker's Health Reference Centers (CEREST), with
      more reported cases in 2011 (n=63; 29.9%); slightly more than half the cases were
      found among men (n=108; 51.2%), the majority aged 18-49 (n=167; 79.1%), in formal
      jobs (n=179; 84.8%) and among service workers and sales persons (n=48; 22.7%);
      the most reported disorder was post-traumatic stress (n=51; 24.2%). CONCLUSION:
      almost all cases were reported in CEREST; despite underreporting, the
      characterization of cases is relevant for informing the construction of a network
      of mental health care in Occupational Health.

PMID- 27869955
TI  - Progress with the Strategic Action Plan for Tackling Chronic Non-Communicable
      Diseases in Brazil, 2011-2015.
AB  - OBJECTIVE: to describe the actions undertaken by the Strategic Action Plan for
      Tackling Chronic Non-Communicable Diseases (NCDs) in Brazil, from 2011 to 2015.
      METHODS: the actions were identified through sectorial and interministerial
      meetings, annual forums, as well as document reviews of publications and laws on
      government websites. RESULTS: the actions found were: national surveys and
      monitoring of mortality and risk factor reduction targets; encouragement of
      physical activity, adequate nutrition and health promotion through the creation
      of the Health Gym Program (Programa Academia da Saude); the publication of
      legislation on tobacco-free environments; free of charge drugs for hypertension,
      diabetes, and asthma; organization of the emergency service network for
      cardiovascular diseases; and expanding access to diagnosis and treatment of
      cancer patients. CONCLUSION: we found progress regarding surveillance, health
      promotion and comprehensive care; in general, the goals of the Plan are being
      met.

PMID- 27869956
TI  - [Aedes aegypti control strategies: a review].
AB  - OBJECTIVE: to describe the main strategies to control Aedes aegypti, with
      emphasis on promising technological innovations for use in Brazil. METHODS: this
      study is a non-systematic review of the literature. Results: several technologies
      have been developed as alternatives in the control of Ae. aegypti, using
      different mechanisms of action, such as selective monitoring of the infestation,
      social interventions, dispersing insecticides, new biological control agents and
      molecular techniques for population control of mosquitoes, also considering the
      combination between them. Evolving technologies require evaluation of the
      effectiveness, feasibility and costs of implementation strategies as
      complementary to the actions already recommended by the National Program for
      Dengue Control. CONCLUSION: the integration of different compatible and effective
      vector control strategies, considering the available technologies and regional
      characteristics, appears to be a viable method to try to reduce the infestation
      of mosquitoes and the incidence of arbovirus transmitted by them.

PMID- 27869957
TI  - Mental disorders record on the Brazilian primary health care information system,
      2014.
AB  - OBJECTIVE: to describe the occurrence of the recording of mental disorders (MD)
      in primary health care (PHC) services in Brazilian municipalities and to analyze
      associated factors. METHODS: an ecological study was conducted using PHC
      Information System secondary data for the year 2014; the magnitude of the
      occurrence of MD recording was assessed through indicators developed for this
      purpose; bivariate analysis was used. RESULTS: 15,216 MD cases were recorded in
      42 (0.8%) municipalities, corresponding to 16.9 MD cases/100,000 inhabitants for
      Brazil, with significant variations between the country's macro-regions; MD
      recording in PHC was most frequent in the Southeast and Southern macro-regions
      (p=0.001), in state capital cities (p<0.001), in municipalities with more than
      200,000 inhabitants (p<0.001), those with PHC coverage greater than 75% (p=0.005)
      and those with Psychosocial Care Centers (p=0.001). CONCLUSION: recording of MD
      in PHC is incipient, unequally distributed and possibly dependent on local
      initiatives.

PMID- 27869958
TI  - [Regional healthcare management support instrument for monitoring health
      indicators].
AB  - OBJECTIVE: to report the development of a computerized tool for regional
      healthcare management to monitor health indicators. METHODS: by means of a
      development survey conducted in 2013, the 'Indicators for Regional Healthcare
      Management' spreadsheet was built in order to evaluate 40 indicators spread over
      seven categories. RESULTS: the tool provides the population age pyramid,
      demographics denominators, a list of the five leading causes of death, and
      reasons for hospital admissions, while the graphs allow the indicators to be
      compared between municipalities within Healthcare Regions; the indicators can be
      updated annually, depending on the availability of results on the website of the
      National Health System Information Technology Department (Datasus). CONCLUSION:
      the tool contains information about the method for calculating indicators and
      accessing sources of information. It has the potential to be used by other
      Healthcare Coordination bodies, and can be used to qualify the continuing
      education of planners and managers, besides assisting with Healthcare Region
      planning.

PMID- 27869959
TI  - [Zika, dengue and chikungunya: challenges and issues].

PMID- 27869960
TI  - Post-2015 agenda strategies for tuberculosis control in Brazil: challenges and
      opportunities.

PMID- 27869961
TI  - [Tools to enhance the quality and transparency of health research reports:
      reporting guidelines].
AB  - Scientific writing is the cornestone for publishing the results of research.
      Reporting guidelines are important tools for all those involved in the process of
      research production and report writing. These guidelines detail what is expected
      to be found in each section of a report for a given study design. The EQUATOR
      Network (Enhancing the QUAlity and Transparency Of health Research) is an
      international initiative that seeks to improve the reliability and the value of
      health research literature by promoting transparent and accurate reporting and
      wider use of robust reporting guidelines. The use of reporting guidelines has
      contributed to improved reports as well as increased quality of research methods.
      Reporting guidelines need to be publicized in order to increase knowledge about
      these essential tools among health researchers. Encouraging their use by journals
      is key to enhancing the quality of scientific publications.

PMID- 27869962
TI  - [Identifying, measuring and valuing health costs].

PMID- 27869963
TI  - [Errata].
AB  - [This corrects the article doi: 10.5123/S1679-49742014000100018].

PMID- 27869964
TI  - Evidences from epidemiological surveillance to the advancement of knowledge
      regarding Zika virus epidemics.

PMID- 27869965
TI  - [New century, new challenges: changes in the burden of disease profile in Brazil,
      1990-2010].
AB  - OBJECTIVE: to describe the burden of disease in Brazil from 1990 to 2010.
      METHODS: analysis of the estimates of the Global Burden of Disease Study 2010 -
      Years of Life Lost due to premature mortality (YLL), Years Lost due to Disability
      (YLD), Disability-Adjusted Life Year (DALY=YLL+YLD) and risk factors. RESULTS:
      there was a decrease in deaths due to diarrhea and an increase in deaths due to
      diabetes and kidney disease, whilst deaths due to homicides and traffic accidents
      remained stable; cardiovascular diseases continued to be the leading cause of
      death despite a 30% reduction; the largest increases in DALY were due to diabetes
      and musculoskeletal diseases in women and alcohol abuse and low back pain in men;
      the main risk factors were poor diet and high blood pressure; smoking, domestic
      pollution and insufficient breastfeeding were found to have reduced. CONCLUSION:
      the rapid epidemiological transition highlights the need to control infectious
      diseases and invest in reducing violence and non-communicable diseases.

PMID- 27869966
TI  - Dengue incidence trend in Brazil, 2002-2012.
AB  - OBJECTIVE: to analyze dengue incidence trend in Brazil from 2002 to 2012.
      METHODS: this was an ecological study with data of the Information System for
      Notifiable Diseases (Sinan); the incidence rate was calculated by age groups,
      states and macroregions, through Prais-Winsten regression. RESULTS: dengue
      incidence rates in Brazil, in 2002 and 2012, were of 401.6 and 301.5 per 100,000
      inhabitants, respectively; annual increment rates were stable (21.4%; 95%CI 
      19.8;83.7) in most of the states, except for Alagoas (38.9%; 95%CI 5.1;83.5) and
      Tocantins (50.4%; 95%CI 12.6;100.7); the North Region was the only region to
      present increase trend in the incidence of dengue. CONCLUSION: although rates
      have remained stable in most of the states, they are still high in Brazil;
      broader public policies focusing on new dengue control strategies are necessary.

PMID- 27869967
TI  - Incidence of dengue cases (2007-2013) and seasonal distribution of mosquitoes
      (Diptera: Culicidae) (2012-2013) in Barreiras, Bahia, Brazil.
AB  - OBJECTIVE: to describe seasonal mosquito distribution and the incidence of dengue
      cases in Barreiras, Bahia, Brazil. METHODS: this is a descriptive study using
      primary data on mosquito distribution in ovitraps from April 2012 to March 2013,
      as well as secondary data from the Notifiable Diseases Information System,
      Epidemiological Surveillance and the Zoonosis Control Center about dengue cases
      and Aedes aegypti infestation rates from January 2007 to March 2013. RESULTS:
      16,512 mosquito specimens were collected, 62.0% were Culex quinquefasciatus (most
      frequent in the dry season) and 38.0% were Aedes aegypti (most frequent in the
      rainy season); 8,373 dengue cases were recorded, with highest incidence per
      100,000 inhabitants in 2009 (n=704.5), 2011 (n=429.3) and 2013 (n=247.2), between
      January and June. CONCLUSION: Culex quinquefasciatus and Aedes aegypti occurred
      in all months; dengue incidence was higher in the rainy season and in alternating
      years.

PMID- 27869968
TI  - Classification of transmission risk of vaccine-preventable diseases based on
      vaccination indicators in Brazilian municipalities.
AB  - OBJECTIVE: to describe the transmission risk classification of vaccine
      preventable diseases in Brazilian municipalities. METHODS: this was a descriptive
      epidemiologic study using 2014 data of the Brazilian National Immunization
      Program Information System; the vaccine coverage indicators were used to classify
      the transmission risk of vaccine-preventable diseases in the municipalities.
      RESULTS: of the 5,570 Brazilian municipalities, 12.0% were classified as very low
      risk, 29.6% as low risk, 2.2% as medium risk, 54.3% as high risk and 1.8% as very
      high risk. CONCLUSION: the vaccination coverage surveillance allowed to identify
      most of the municipalities in high risk situation and the minority of children
      living in municipalities with appropriate coverage; the vaccination coverage
      surveillance using indicators of the Brazilian National Health System (SUS) is a
      new tool for identifying priority areas where the actions can be more successful
      for health managers and improve the quality and the success of the immunizations
      program.

PMID- 27869969
TI  - Influenza vaccination among elderly in Pelotas-RS, Brazil, 2014: a population
      based study.
AB  - OBJECTIVE: to describe the prevalence of individuals vaccinated against influenza
      and associated factors with vaccination among elderly; identify reasons for
      noncompliance and adverse events. METHODS: this was a cross-sectional study,
      conducted in the urban area of Pelotas-RS, Brazil, in 2014. RESULTS: out of 1,451
      elderly, 71% got vaccinated; the highest prevalences were observed in the elderly
      with better economic status (PR=1.2 - 95%CI 1.1;1.4), those who were not employed
      (PR=1.2 - 95%CI 1.1;1.3), those who were physically active (PR=1.1 - 95%CI
      1.0;1.2), former smokers (PR=1.3 - 95%CI 1.1;1.5), those who were assisted by a
      health professional the previous year (PR=1.2 - 95%CI 1.1;1.4) and those who
      reported two or more health problems (PR=1.2 - 95%CI 1.1;1.4); the main reason
      for noncompliance (n=414) was 'did not want/do not like' (45%); the most
      frequently reported adverse events were malaise (49/83) and muscle ache (30/83).
      CONCLUSION: vaccination coverage was not universal; educational approaches are
      needed to clarify controversy on the efficacy, adverse events and benefits of
      vaccination.

PMID- 27869971
TI  - Time trend of lack of access to health services in Brazil, 1998-2013.
AB  - OBJECTIVE: to analyze the time trend on the demand and lack of access to public
      health services in Brazil. METHODS: this is a panel of cross-sectional studies
      with data of the National Household Sample Survey (1998, 2003, 2008) and the
      National Health Survey (2013); the prevalence of demand and lack of access within
      the fifteen days prior to the survey was estimated; Poisson regression was used
      for trend analysis. RESULTS: the demand for health services increased from 13.0%
      (95%CI 12.3;13.7), in 1998, to 15.0% (95%CI 14.5;15.4), in 2013; the lack of
      access remained stable, being of 3.7% (95%CI 3.2;4.2) in 1998 and 4.5% (95%CI
      4.0;5.0) in 2013. CONCLUSIONS: the increase in demand for health services and the
      stability in the lack of access indicate improvements in the Brazilian public
      health system performance; additional efforts are required to ensure universal
      access to public health services in Brazil.

PMID- 27869970
TI  - [Municipalities Stratification for Health Performance Evaluation].
AB  - OBJECTIVE: to propose and present a stratification of Brazilian municipalities
      into homogeneous groups for evaluation studies of health management performance.
      METHODS: this was a methodological study, with selected indicators which classify
      municipalities according to conditions that influence the health management and
      population size; data for the year 2010 were collected from demographic and
      health databases; correlation tests and factor analysis were used. RESULTS: seven
      strata were identified - Large-sized; Medium-sized with favorable, regular or
      unfavorable influences; and Small-sized with favorable, regular or unfavorable
      influences -; there was a concentration of municipalities with favorable
      influences in strata with better purchasing power and funding, as well as a
      concentration of municipalities with unfavorable influences in the North and
      Northeast regions. CONCLUSION: the proposed classification grouped similar
      municipalities regarding influential factors in health management, which allowed
      the identification of comparable groups of municipalities, setting up a
      consistent alternative to performance evaluation studies.

PMID- 27869972
TI  - Effectiveness of psychosocial care in school continuity of adolescents in social
      vulnerability.
AB  - OBJECTIVE: to study the effectiveness of a psychosocial care program in school
      continuity of adolescents in social vulnerability. METHODS: this was a
      retrospective cohort study involving 200 adolescents assisted in a
      multidisciplinary intervention program with harm reduction approach, from 2007 to
      2012; the intervention effect was assessed using Poisson regression models.
      RESULTS: 200 adolescents were included in the program; 116 of them continued and
      84 dropped it; 74.5% were attending school after six month, with a higher
      proportion among those who adhered to the intervention (RR=1.12 - 95%CI
      1.01;1.27); and those who were studying when they joined the program (RR=8.52 -
      95%CI 3.71;19.57). CONCLUSION: the evaluated program has a positive effect on
      rehabilitation and school continuity of adolescents in social vulnerability, but
      individual characteristics, such as being studying already, play a dominant role
      in the adherence to the program.

PMID- 27869973
TI  - [Characteristics of the notification of violence against children in the
      municipality of Ribeirao Preto, Sao Paulo, Brazil].
AB  - OBJECTIVE: to describe the cases of violence against children reported in
      Ribeirao Preto-SP, Brazil. METHODS: this was a descriptive study using data
      provided by the Violence and Accidents Surveillance System (VIVA), of the
      Municipal Health Department of Ribeirao Preto-SP, Brazil, from 2006 to 2008.
      RESULTS: a total of 498 cases of violence against children (0-9 years old) were
      reported in the period, with an increase in the number of notifications, from 112
      in 2006 to 197 in 2008; 79.3% of the notifications came from the Health area; and
      most children were female (56.4%), aged between two and five years old (over
      60%); most aggressors were male (53.6%) and the father figure stood out (22.7%);
      physical aggressions were the most frequent (59.2%) and the most frequent place
      of the occurrence was the family household (75.5%). CONCLUSION: most victims were
      female, abused by men, mostly fathers and other family members, at the family
      household.

PMID- 27869974
TI  - [Evaluating productivity targets achievement in Dental Specialty Centers from
      Maranhao State, Brazil, 2011].
AB  - OBJECTIVE: to evaluate productivity targets achievement (PTA) in Dental Specialty
      Centers (DSCs) from Maranhao State, Brazil. METHODS: this was an ecologic study
      using secondary data; an indicator for PTA was created for each subgroup of
      procedures. RESULTS: 25 DSCs were evaluated; the PTA was higher for basic
      procedures (n=19), followed by endodontics (n=11), oral surgery (n=9) and
      periodontics (n=8); the best results were obtained at DSCs type II; higher PTA
      was associated with financial anticipation (basic procedures) and higher Human
      Development Index, life expectancy and social exclusion rate (endodontics); lower
      PTA was associated with larger population (endodontics/oral surgery), adherence
      to the Pact for Health (periodontics/endodontics), larger number of specialties
      (periodontics) and bigger DSC (oral surgery). CONCLUSION: most DSCs did not
      achieve productivity targets, except for basic procedures; socioeconomic and
      health management characteristics of the municipalities were associated with the
      PTA; the DSCs characteristics explained little about the PTA.

PMID- 27869975
TI  - [Oral health knowledge and practices among pregnant women using health services
      in Sao Luis, Maranhao, Brazil, 2007-2008].
AB  - OBJECTIVE: to describe characteristics of oral health care during prenatal check
      ups and knowledge about oral health among pregnant women using public and private
      health services in Sao Luis, Maranhao, Brazil. METHODS: this is a descriptive
      study of 300 women interviewed in public health services and a further 300
      interviewed in private health services between August 2007 and July 2008.
      RESULTS: tooth brushing frequency was similar among users of public and private
      services (p=0.156), while flossing (64.0% and 47.0%; p<0.001) and mouthwashing
      (39.7% and 27.0%; p=0.001) was more frequent among private service users in
      relation to public service users; most users of public services (60.3%) and
      private services (65.7%) were unaware of the association between oral health and
      pregnancy. CONCLUSION: frequency of tooth brushing was similar among pregnant
      women in public and private services; the effects of pregnancy on oral health
      were not well known.

PMID- 27869976
TI  - [Characterization of the physical environment and practice of physical activities
      in Primary Health Care Units in Guarapuava, Parana State, Brazil, 2011-2012].
AB  - OBJECTIVE: to characterize the physical environment and physical activity (PA) in
      Primary Health Care Units (PHU) in the urban area of Guarapuava-PR, Brazil, 2011
      2012. METHODS: this is a descriptive study in which the coordinators of the
      municipality's 27 PHUs were interviewed about violence, crime and physical space
      and safety conditions for PAs inside and outside the PHUs; the streets
      surrounding the area were visited to evaluate environmental factors categorized
      as favorable or unfavorable to PA deployment and practice. RESULTS: the most
      common places for PA were grass areas (n=18) and churches (n=24); three fifths of
      PHUs presented factors favorable to PA deployment/practice; lack of sidewalks (14
      PHUs) or uneven sidewalks (13 PHUs) surrounding the PHUs are conditions that
      could jeopardize the practice of walking. CONCLUSION: despite the identification
      of favorable factors for PA practice, at PHUs should be focused by health service
      managers.

PMID- 27869977
TI  - Methods and procedures used in Aedes aegypti control in the successful campaign
      for yellow fever prophylaxis in Rio de Janeiro, Brazil, in 1928 and 1929.
AB  - OBJECTIVE: to review the challenges and procedures used in Aedes aegypti control
      and the characteristics of the epidemics in the successful campaign, led by
      Clementino Fraga, for yellow fever control in Rio de Janeiro, Brazil, in 1928 and
      1929, before the vaccine (1937) and DDT (1947). METHODS: a literature review was
      conducted by searching official reports, scientific journals and historic
      textbooks on this subject. RESULTS: the A. aegypti control was achieved through
      the hard and organized work of breeding site police teams, priority in
      eliminating breeding sites through environmental management measures and a
      qualified training program for the teams. CONCLUSION: the reports demonstrate a
      set of simple but laborious procedures that could effectively control mosquitoes
      in urban environment through the work of the teams, who were committed to
      environmental management measures, aiming at eliminating breeding sites and were
      capable of handling social and environmental obstacles.

PMID- 27869978
TI  - Why should Brazil give priority to depression treatment in health resource
      allocation?

PMID- 27869980
TI  - Analytical models in economic evaluation studies.

PMID- 27869979
TI  - Assessing the completeness and agreement of variables of the Information Systems
      on Live Births and on Mortality in Recife-PE, Brazil, 2010-2012.
AB  - OBJECTIVE: to assess the information completeness and agreement on infant deaths.
      METHODS: this was an evaluation study with descriptive design using data of the
      Information System on Live Births (Sinasc) and Mortality Information System (SIM)
      of residents in Recife-PE, Brazil, in 2010-2012; the deterministic records
      linkage was used to combine the data on infant deaths and live births. RESULTS:
      of the 837 infant deaths registered on SIM, 811 (96.9%) were linked; the
      completeness obtained was above 95% on SIM and 98% on Sinasc; the agreement
      varied from 0.762 (substantial) to 0.997 (excellent) for the intraclass
      correlation coefficient, and it was excellent for Kappa index (>0.80).
      CONCLUSION: Sinasc and SIM presented excellent completeness and agreement for
      most of the variables analyzed. The relationship between the databases is a tool
      that can be used by the health services of the municipalities to improve the
      vital statistics information systems.

PMID- 27869982
TI  - Characteristics of the first cases of microcephaly possibly related to Zika virus
      reported in the Metropolitan Region of Recife, Pernambuco State, Brazil.
AB  - OBJECTIVE: to describe the first cases of microcephaly possibly related to Zika
      virus in live born babies reported in the Metropolitan Region of Recife,
      Pernambuco State, Brazil. METHODS: this was a descriptive case series study
      (cases reported between August 1st and October 31st 2015), using medical record
      data and data from a questionnaire answered by the mothers of the babies.
      RESULTS: 40 microcephaly cases were confirmed, distributed in eight
      municipalities within the Metropolitan Region, with Recife itself having the
      highest concentration of cases (n=12); median head circumference was 29 cm,
      median chest girth was 31 cm and median weight was 2,628 grams; 21/25 cases had
      brain calcification, ventriculomegaly or lissencephaly; 27 of the 40 mothers
      reported rash during pregnancy, 20 in the first trimester and 7 in the second
      trimester, as well as itching, headache, myalgia and absence of fever.
      CONCLUSION: the majority of the cases bore the characteristics of congenital
      infection; the clinical condition of the majority of mothers suggested Zika virus
      infection during pregnancy.

PMID- 27869981
TI  - Description of the first cases of Zika virus fever investigated in municipalities
      of the Brazilian Northeastern Region, 2015.
AB  - OBJECTIVE: to confirm Zika virus circulation and discard other etiological agents
      in an outbreak occurred in the states of Rio Grande do Norte, Maranhao and
      Paraiba, in May, 2015. METHODS: this is a case series descriptive study with
      residents in Natal-RN, Barra do Corda-MA, Sao Luis-MA and Joao Pessoa-PB, with 20
      cases in each state, presenting rash, absent or mild fever and one of the
      following signs/symptoms: conjunctival hyperemia, arthralgia or limb edema; RT
      PCR/isolation tests for Zika, enterovirus and respiratory viruses, and serology
      tests (dengue, rubella and parvovirus B19) were performed. RESULTS: the main
      symptoms were rash (n=60), pruritus (n=54), and arthralgia (n=47); 51 individuals
      did not present fever; Zika virus was identified in 18 cases (12 in Paraiba, four
      in Maranhao and two in Rio Grande do Norte), and antibodies to dengue, in 14
      cases. CONCLUSION: the symptoms were consistent with Zika virus fever; there was
      laboratory confirmation for Zika and dengue.

PMID- 27869983
TI  - Microcephaly in Brazil: prevalence and characterization of cases from the
      Information System on Live Births (Sinasc), 2000-2015.
AB  - OBJECTIVE: to describe the prevalence coefficients and characterize cases of
      microcephaly at birth in Brazil from 2000-2015. METHODS: this is a descriptive
      study with data from the Information System on Live Births (Sinasc). The
      coefficients were calculated by region and characteristics of mothers and live
      births (LB). RESULTS: the annual average number of microcephaly cases was 164 for
      the period 2000-2014, whilst in 2015, 1,608 cases were registered (54.6 cases per
      100 thousand LB). Higher coefficients were observed among preterm babies (81.7;
      95%CI 72.3;92.2), born from black-skinned (70.9; 95%CI 58.5;85.9) or to brown
      skinned (71.5; 95%CI67.4;75.8) women, to women aged <=19 (70.3; 95%CI 63.5;77.8)
      or >=40 (62.1; 95%CI 46.6;82.6), with <=3 years of study (73.4; 95%CI 58.2;92.4)
      and residents in the Northeast region (138.7; 95%CI 130.9;147.0). CONCLUSION: the
      high number of microcephaly cases in 2015 reinforces the importance of Sinasc and
      the need to improve the surveillance of congenital anomalies.

PMID- 27869984
TI  - Cesarean delivery rates and obstetric culture - an Italian register-based study.
AB  - INTRODUCTION: Cesarean delivery rates are rising due to multiple factors,
      including less use of operative vaginal delivery and vaginal birth after cesarean
      delivery, which often reflect local obstetric practices. Objectives of the study
      were to analyze the relations between cesarean delivery, these practices, and
      perinatal outcomes. MATERIAL AND METHODS: We included all deliveries in the 72
      hospitals of Lombardia, a region in northern Italy, during the year 2013. The
      delivery certificate was used as data source. Pearson's correlation coefficient
      and logistic regression were used for statistical analysis. RESULTS: We included
      87 896 deliveries. The number of deliveries per hospital ranged from 140 to 6123.
      The rate of cesarean delivery was 28.3% (range 9.9-86.4%), operative vaginal
      delivery 4.7% (range 0.2-10.0%), and vaginal birth after cesarean 17.3% (range 0
      79.2%). We found a significant inverse correlation between rates of overall
      cesarean delivery and operative vaginal delivery (r = -0.25, p = 0.04). The
      correlation between rate of overall cesarean delivery and vaginal birth after
      cesarean was also inverse and significant (r = -0.57, p < 0.001). There was no
      association between overall cesarean delivery rate and the rates of Apgar score
      at 5 min <7 in term and late preterm neonates (r = -0.92, p = 0.46) and of
      perinatal mortality (r = -0.19, p = 0.13), respectively. The associations were
      independent of hospital volume of activity. CONCLUSIONS: An obstetric practice
      that encourages vaginal instrumental delivery in delayed second stage of labor or
      vaginal birth after previous cesarean delivery, could reduce the rising cesarean
      delivery rate. This will require a change in obstetric culture, continuing
      education of healthcare providers, and leadership.

PMID- 27869985
TI  - Agreement and accuracy using the FIGO, ACOG and NICE cardiotocography
      interpretation guidelines.
AB  - INTRODUCTION: One of the limitations reported with cardiotocography is the modest
      interobserver agreement observed in tracing interpretation. This study compared
      agreement, reliability and accuracy of cardiotocography interpretation using the
      International Federation of Gynecology and Obstetrics, American College of
      Obstetrics and Gynecology and National Institute for Health and Care Excellence
      guidelines. MATERIAL AND METHODS: A total of 151 tracings were evaluated by 27
      clinicians from three centers where International Federation of Gynecology and
      Obstetrics, American College of Obstetrics and Gynecology and National Institute
      for Health and Care Excellence guidelines were routinely used. Interobserver
      agreement was evaluated using the proportions of agreement and reliability with
      the kappa statistic. The accuracy of tracings classified as
      "pathological/category III" was assessed for prediction of newborn acidemia. For
      all measures, 95% confidence interval were calculated. RESULTS: Cardiotocography
      classifications were more distributed with International Federation of Gynecology
      and Obstetrics (9, 52, 39%) and National Institute for Health and Care Excellence
      (30, 33, 37%) than with American College of Obstetrics and Gynecology (13, 81,
      6%). The category with the highest agreement was American College of Obstetrics
      and Gynecology category II (proportions of agreement = 0.73, 95% confidence
      interval 0.70-76), and the ones with the lowest agreement were American College
      of Obstetrics and Gynecology categories I and III. Reliability was significantly
      higher with International Federation of Gynecology and Obstetrics (kappa = 0.37,
      95% confidence interval 0.31-0.43), and National Institute for Health and Care
      Excellence (kappa = 0.33, 95% confidence interval 0.28-0.39) than with American
      College of Obstetrics and Gynecology (kappa = 0.15, 95% confidence interval 0.10
      0.21); however, all represent only slight/fair reliability. International
      Federation of Gynecology and Obstetrics and National Institute for Health and
      Care Excellence showed a trend towards higher sensitivities in prediction of
      newborn acidemia (89 and 97%, respectively) than American College of Obstetrics
      and Gynecology (32%), but the latter achieved a significantly higher specificity
      (95%). CONCLUSIONS: With American College of Obstetrics and Gynecology guidelines
      there is high agreement in category II, low reliability, low sensitivity and high
      specificity in prediction of acidemia. With International Federation of
      Gynecology and Obstetrics and National Institute for Health and Care Excellence
      guidelines there is higher reliability, a trend towards higher sensitivity, and
      lower specificity in prediction of acidemia.

PMID- 27869986
TI  - Physical Exercise for Late-Life Depression: Customizing an Intervention for
      Primary Care.
AB  - OBJECTIVES: To identify which individual- and context-related factors influence
      the translation into clinical practice of interventions based on physical
      exercise (PE) as an adjunct to antidepressants (AD) for the treatment of late
      life major depression (LLMD). DESIGN: Secondary analysis of a randomized
      controlled trial. SETTING: Primary care with psychiatric consultation-liaison
      programs (PCLPs)-organizational protocols that regulate the clinical management
      of individuals with psychiatric disorders. PARTICIPANTS: Individuals aged 65 and
      older with major depression according to the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition (N = 121). INTERVENTION: Participants with LLMD
      were randomized to AD (sertraline) or AD plus PE (AD + PE). MEASUREMENTS:
      Participant characteristics that were associated with greater effectiveness of AD
      + PE (moderators) were identified, and effect sizes were calculated from success
      rate differences. Whether the characteristics of the study setting influenced
      participant flow and attendance at exercise sessions was then explored, and
      primary care physicians (PCPs) were surveyed regarding their opinions on PE as a
      treatment for LLMD. RESULTS: The following participant characteristics were
      associated with greater likelihood of achieving remission from depression with AD
      + PE than with AD alone: aged 75 and older (effect size 0.32), polypharmacy
      (0.35), greater aerobic capacity (0.48), displaying psychomotor slowing (0.49),
      and less-severe anxiety (0.30). The longer the PCLP had been established at a
      particular center, the more individuals were recruited at that center. After
      participating in the study, PCPs expressed positive views on AD + PE as a
      treatment for LLMD and were more likely to use this as a therapeutic strategy.
      CONCLUSIONS: The combination of PE and sertraline could improve the management of
      LLMD, especially when customized for individuals with specific clinical features.
      Liaison programs might influence the implementation of similar interventions in
      primary care, and PCPs viewed them positively.

PMID- 27869987
TI  - The role of competition, ecotones, and temperature in the elevational
      distribution of Himalayan birds.
AB  - There is clear evidence that species' ranges along environmental gradients are
      constrained by both biotic and abiotic factors, yet their relative importance in
      structuring realized distributions remains uncertain. We surveyed breeding bird
      communities while collecting in situ temperature and vegetation data along five
      elevational transects in the Himalayas differing in temperature variability,
      habitat zonation, and bird richness in order to disentangle temperature, habitat,
      and congeneric competition as mechanisms structuring elevational ranges. Our
      results from species' abundance models representing these three mechanisms
      differed markedly from previous, foundational research in the tropics. Contrary
      to general expectations, we found little evidence for competition as a major
      determinant of range boundaries, with congeneric species limiting only 12% of
      ranges. Instead, temperature and habitat were found to structure the majority of
      species' distributions, limiting 48 and 40% of ranges, respectively. Our results
      suggest that different mechanisms may structure species ranges in the temperate
      Himalayas compared to tropical systems. Despite recent evidence suggesting
      temperate species have broader thermal tolerances than tropical species, our
      findings reinforce the notion that the abiotic environment has significant
      control over the distributions of temperate species.

PMID- 27869988
TI  - Corrigendum.

PMID- 27869989
TI  - Association of Positive and Negative Syndrome Scale (PANSS) short forms with
      global functioning and quality of life.

PMID- 27869990
TI  - Association of Positive and Negative Syndrome Scale short forms with global
      functioning and quality of life.

PMID- 27869991
TI  - Reactive aggression in young patients with ADHD-a critical role for small
      provocations.

PMID- 27869992
TI  - Electroconvulsive therapy and cognition: a salutary reappraisal.

PMID- 27869995
TI  - Special Issue on 'Microbe-host interactions'.

PMID- 27869994
TI  - Neighborhood Disadvantage and Life-Space Mobility Are Associated with Incident
      Falls in Community-Dwelling Older Adults.
AB  - OBJECTIVES: To determine the relationship between neighborhood-level
      socioeconomic characteristics, life-space mobility, and incident falls in
      community-dwelling older adults. DESIGN: Prospective, observational cohort study
      with a baseline in-home assessment and 6-month telephone follow-up. SETTING:
      Central Alabama. PARTICIPANTS: Community-dwelling adults aged 65 and older
      recruited from a random sample of Medicare beneficiaries (N = 1,000).
      MEASUREMENTS: Neighborhood disadvantage was measured using a composite index
      derived from baseline neighborhood-level residential census tract socioeconomic
      variables. Data on individual-level socioeconomic characteristics, clinical
      variables, and life-space collected at baseline were included as covariates in a
      multivariate model using generalized estimating equations to assess the
      association with incident falls in the 6 months after baseline. RESULTS: Of the
      940 participants who completed baseline and follow-up assessments, 126 (13%)
      reported one or more new falls in the 6 months after baseline. There was an
      independent nonlinear association between neighborhood disadvantage (according to
      increasing quartiles of disadvantage) and incident falls after adjusting for
      confounders: The lowest quartile served as reference; 2nd quartile odds ratio
      (OR) = 2.4, 95% confidence interval (CI) = 1.2-4.6; 3rd quartile OR = 1.9, 95% CI
      = 1.0-3.7; 4th quartile OR = 3.2, 95% CI = 1.7-6.0. Each 10-point decrement in
      life-space (OR = 1.2, 95% CI = 1.0-1.3) was associated with a higher risk of
      falls. CONCLUSION: Greater neighborhood disadvantage was associated with greater
      risk of falls. Life-space also contributes separately to fall risk. Community
      dwelling older adults in disadvantaged neighborhoods, particularly those with
      limited mobility, may benefit from a more-rigorous assessment of their fall risk
      by healthcare providers. Neighborhood level socioeconomic characteristics should
      also be an important consideration when identifying vulnerable populations that
      may benefit the most from fall prevention programs.

PMID- 27869997
TI  - Olfactory Aura: A Missing Tool?

PMID- 27869996
TI  - Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To evaluate the efficacy of noninvasive brain stimulation (NIBS) on
      pain control in migraine patients. BACKGROUND: Recent studies have used NIBS as
      an abortive and prophylactic treatment for migraine; however, its efficacy
      regarding meaningful clinical effects remains to be critically analyzed. DESIGN:
      Systematic review of controlled clinical trials. METHODS: Searches were conducted
      in six databases: MEDLINE (via PubMed), LILACS (via BIREME), CINAHL (via EBSCO),
      Scopus (via EBSCO), Web of Science, and CENTRAL. Two independent authors searched
      for randomized controlled clinical trials published through until January 2016
      that involved the use of transcranial direct current stimulation (tDCS) and
      transcranial magnetic stimulation (TMS) in migraineurs. Studies which met the
      eligibility criteria were assessed and methodological quality was examined using
      the Cochrane tool for assessing risk of bias. Information about pain intensity
      (primary outcome), migraine attacks, painkiller intake, and adverse effects were
      extracted. RESULTS: Eight studies were included in the quantitative analysis with
      153 migraine patients that received NIBS and 143 sham NIBS. In overall meta
      analysis, we did not find significant results for pain intensity (SMD: -0.61; CI:
      -1.35 to 0.13; P = .11), for migraine attacks (SMD: -0.44; 95%; CI: -1.15 to
      0.26; P = .22), and for painkiller intake (SMD: -0.57; 95% CI: -1.21 to 0.07; P =
      .08). However, subgroup analysis considering only tDCS effects have demonstrated
      a decrease for pain intensity (SMD: -0.91; 95% CI: -1.79 to -0.03; P = .04),
      migraine attacks (SMD: -0.75; 95% CI: -1.25 to -0.24; P = .004), and painkiller
      intake (SMD: -0.64; 95% CI: -1.21 to -0.07; P = .03). Subgroup analysis for TMS
      did not reveal significant effects for any outcome. CONCLUSION: Low or very low
      quality of evidence suggests that our primary outcome evaluation failed to find
      support for the superiority of NIBS over sham treatment. Although, subgroup
      analysis reveals that tDCS have moderate to high effects and could be a promising
      nonpharmacological alternative to pain control, mainly for painkiller intake
      reduction. However, there is a need for larger controlled trials with
      methodological rigor, which could increase the power of result inference.

PMID- 27869998
TI  - Response to: Guidelines for the clinical use in epilepsy surgery evaluation of
      magnetoencephalography and electroencephalography for source localization.

PMID- 27870000
TI  - Erratum.

PMID- 27869999
TI  - Guidelines for the clinical use in epilepsy surgery evaluation of
      magnetoencephalography and electroencephalography for source localization.

PMID- 27870001
TI  - The new definition and classification of status epilepticus: What are the
      implications for children?

PMID- 27870002
TI  - Retraction.

PMID- 27870003
TI  - Prognostic impact of the putative cancer stem cell markers ABCG2, CD133, ALDH1A1
      and CD44V7/8 in metastatic melanoma.

PMID- 27870004
TI  - False and mycoplasma-contaminated leukemia-lymphoma cell lines: time for a
      reappraisal.
AB  - Leukemia-lymphoma cell lines are important research tools in a variety of fields.
      To represent adequate model systems it is of utmost importance that cell lines
      faithfully model the primary tumor material and are not cross-contaminated with
      unrelated cell material (or contaminated with mycoplasma). As it has been
      previously reported that cross-contaminated cell lines represent a significant
      problem, it is of interest to know whether any improvement in the prevalence of
      such "false cell lines" had occurred since we called the alert in 1999. A
      retrospective review of our data archives covered 848 cell lines received from
      1990 to 2014 from 290 laboratories in 23 countries spanning the spectrum of
      leukemia-lymphoma entities. Two variables were considered: authenticity and
      freedom from mycoplasma infection. Regarding provenance, we separately considered
      primary sources (original investigators having established the cell lines or
      reference repositories) and secondary sources. The percentages of mycoplasma
      contaminated cell lines decreased significantly over the 25-year timespan. Among
      primary sourced material: mycoplasma-contamination fell from 23% to 0%; among
      secondary sourced: from 48% to 21%. The corresponding figures for cross
      contamination declined from 15% to 6%, while among material obtained from
      secondary sources prevalence remained remarkably high, throughout the time
      periods at 14-18%. Taken together, our data indicate that using non-authenticated
      cell lines from secondary sources carries a risk of about 1:6 for obtaining a
      false cell line. The use of authentic leukemia-lymphoma cell lines holds
      important translational value for their model character and the reproducibility
      of the laboratory data in the clinical arena.

PMID- 27870005
TI  - HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease
      inhibitors while developing more potent NO-hybridized derivatives?
AB  - The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option
      for the treatment of cancer primarily originated from their success in treating
      HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed
      to immune reconstitution and better control of oncogenic viral infections, the
      number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma
      and prostate cancer suggest other mechanisms for the anti-neoplastic activity of
      PIs. However, a major drawback for the possible adoption of HIV-PIs in the
      therapy of cancer relies on their relatively weak anticancer potency and
      important side effects. This has propelled several groups to generate derivatives
      of HIV-PIs for anticancer use, through modifications such as attachment of
      different moieties, ligands and transporters, including saquinavir-loaded folic
      acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In
      this article, we discuss the current preclinical and clinical evidences for the
      potential use of HIV-PIs, and of novel derivatives, such as saquinavir-NO in the
      treatment of cancer.

PMID- 27870007
TI  - Erratum.

PMID- 27870008
TI  - Phenotypic plasticity of nest timing in a post-glacial landscape: how do reptiles
      adapt to seasonal time constraints?
AB  - Life histories evolve in response to constraints on the time available for growth
      and development. Nesting date and its plasticity in response to spring
      temperature may therefore be important components of fitness in oviparous
      ectotherms near their northern range limit, as reproducing early provides more
      time for embryos to complete development before winter. We used data collected
      over several decades to compare air temperature and nest date plasticity in
      populations of painted turtles and snapping turtles from a relatively warm
      environment (southeastern Michigan) near the southern extent of the last glacial
      maximum to a relatively cool environment (central Ontario) near the northern
      extent of post-glacial recolonization. For painted turtles, population-level
      differences in reaction norm elevation for two phenological traits were
      consistent with adaptation to time constraints, but no differences in reaction
      norm slopes were observed. For snapping turtle populations, the difference in
      reaction norm elevation for a single phenological trait was in the opposite
      direction of what was expected under adaptation to time constraints, and no
      difference in reaction norm slope was observed. Finally, among-individual
      variation in individual plasticity for nesting date was detected only in the
      northern population of snapping turtles, suggesting that reaction norms are less
      canalized in this northern population. Overall, we observed evidence of
      phenological adaptation, and possibly maladaptation, to time constraints in long
      lived reptiles. Where present, (mal)adaptation occurred by virtue of differences
      in reaction norm elevation, not reaction norm slope. Glacial history, generation
      time, and genetic constraint may all play an important role in the evolution of
      phenological timing and its plasticity in long-lived reptiles.

PMID- 27870006
TI  - Prediagnostic circulating concentrations of plasma insulin-like growth factor-I
      and risk of lymphoma in the European Prospective Investigation into Cancer and
      Nutrition.
AB  - Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the
      hypothesis that circulating IGF-I concentration is related to risk of lymphoma
      overall or its subtypes has not been examined prospectively. IGF-I concentration
      was measured in pre-diagnostic plasma samples from a nested case-control study of
      1,072 cases of lymphoid malignancies and 1,072 individually matched controls from
      the European Prospective Investigation into Cancer and Nutrition. Odds ratios
      (ORs) and confidence intervals (CIs) for lymphoma were calculated using
      conditional logistic regression. IGF-I concentration was not associated with
      overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third
      = 0.77 [95% CI = 0.57-1.03], ptrend  = 0.06). There was no statistical evidence
      of heterogeneity in this association with IGF-I by sex, age at blood collection,
      time between blood collection and diagnosis, age at diagnosis, or body mass index
      (pheterogeneity for all  >= 0.05). There were no associations between IGF-I
      concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin
      lymphoma, although number of cases were small. In this European population, IGF-I
      concentration was not associated with risk of overall lymphoma. This study
      provides the first prospective evidence on circulating IGF-I concentrations and
      risk of lymphoma. Further prospective data are required to examine associations
      of IGF-I concentrations with lymphoma subtypes.

PMID- 27870010
TI  - Context-dependent landscape of fear: algal density elicits risky herbivory in a
      coral reef.
AB  - Foraging theory posits that isolation from refuge habitat within a landscape
      increases perceived predation risk and, thus, suppresses the foraging behavior of
      prey species. However, these effects may depend fundamentally on resource
      availability, which could affect prey boldness and can change considerably
      through bottom-up processes. We conducted a field survey and experiment in a
      coral reef to test the effects of isolation from refuge habitat (i.e., reef
      structure) on herbivory by reef fishes and whether these effects depend on
      resource density. By fitting continuous-time, pure death Markov processes to our
      data, we found that at both the local and landscape scale distance from refuge
      habitat reduced herbivory in attractive resource patches of palatable benthic
      algae. However, our field experiment revealed that higher initial resource
      densities weakened negative effects of distance from refuge habitat on herbivory.
      Furthermore, we observed higher bite rates and greater total lengths of
      herbivorous fishes with greater distance from refuge habitat-responses consistent
      with higher perceived predation risk. Our results suggest that while the loss or
      fragmentation of refuge habitat reduces consumer control of resources, greater
      resource densities can partially counteract this effect by altering landscapes of
      fear of consumer species. Our findings emphasize the importance of considering
      the spatial context of species interactions that structure communities.

PMID- 27870009
TI  - Photosynthetic rates influence the population dynamics of understory herbs in
      stochastic light environments.
AB  - Temporal variability in light from gaps in the tree canopy strongly influences
      the vital rates of understory plants. From 2012 to 2015, we estimated the size
      specific vital rates of two herbs, Calathea crotalifera and Heliconia tortuosa,
      over a range of light environments. We estimated maximum photosynthetic capacity
      (Amax ) for a subset of individuals each year during three annual censuses, and
      modelled future size as a linear function of current size (a plant trait that
      changes ontogenetically), canopy openness (an environmental variable), and Amax
      (a potentially plastic physiological trait). We estimated what the demographic
      success would be of a population comprised of individuals with a particular fixed
      Amax for each of several levels of canopy openness if the environment remained
      constant, by evaluating corresponding Integral Projection Models and their
      deterministic growth rates (lambda). We then estimated their demographic success
      in the stochastic light environment (lambdaS ) and its elasticities. As light
      increased, deterministic lambda increased for Calathea by 33% but decreased for
      Heliconia by 52%, and increasing Amax had no effect on lambda for Calathea but
      increased lambda for Heliconia in low light. As Amax increased, lambdaS increased
      for Heliconia, but not Calathea. We also investigated whether photosynthetic
      rates would influence the elasticities of lambdaS, including its response to
      perturbation of vital rates in each environment (ESbeta ), vital rates over all
      environments (ES ), and variability of vital rates among environments (ESsigma ).
      ES , ESsigma , and ESbeta were influenced by Amax for Heliconia but not Calathea.
      Events that affect some vital rates in high light have a greater impact on
      overall fitness than events that affect the same vital rates in shady
      environments, and there is greater potential for selection on traits of large
      individuals in high light than in low light for Heliconia, while the reverse was
      true for Calathea. Photosynthetic rates, through their effects on growth, can
      strongly influence the population dynamics of plants in random light
      environments, but the magnitude of this effect varies between species. In the
      species for which fitness was independent of Amax , Calathea, there would be
      little opportunity for selection on photosynthetic rates.

PMID- 27870011
TI  - Effects of dispersal and environmental heterogeneity on the replacement and
      nestedness components of beta-diversity.
AB  - Traditionally metacommunity studies have quantified the relative importance of
      dispersal and environmental processes on observed beta-diversity. Separating beta
      diversity into its replacement and nestedness components and linking such
      patterns to metacommunity drivers can provide richer insights into biodiversity
      organization across spatial scales. It is often very difficult to measure actual
      dispersal rates in the field and to define the boundaries of natural
      metacommunities. To overcome those limitations, we revisited an experimental
      metacommunity dataset to test the independent and interacting effects of
      environmental heterogeneity and dispersal on each component of beta-diversity. We
      show that the balance between the replacement and nestedness components of beta
      diversity resulting from eutrophication changes completely depending on dispersal
      rates. Nutrient enrichment negatively affected local zooplankton diversity and
      generated a pattern of beta-diversity derived from nestedness in unconnected,
      environmentally heterogeneous landscapes. Increasing dispersal erased the pattern
      of nestedness, whereas the replacement component gained importance. In
      environmentally homogeneous metacommunities, dispersal limitation created
      community dissimilarity via species replacement whereas the nestedness component
      remained low and unchanged across dispersal levels. Our study provides novel
      insights into how environmental heterogeneity and dispersal interact and shape
      metacommunity structure.

PMID- 27870012
TI  - Above- and belowground insect herbivory modifies the response of a grassland
      plant community to nitrogen eutrophication.
AB  - Understanding the role that species interactions play in determining the rate and
      direction of ecosystem change due to nitrogen (N) eutrophication is important for
      predicting the consequences of global change. Insects might play a major role in
      this context. They consume substantial amounts of plant biomass and can alter
      competitive interactions among plants, indirectly shaping plant community
      composition. Nitrogen eutrophication affects plant communities globally, but
      there is limited experimental evidence of how insect herbivory modifies plant
      community response to raised N levels. Even less is known about the roles of
      above- and belowground herbivory in shaping plant communities, and how the
      interaction between the two might modify a plant community's response to N
      eutrophication. We conducted a 3-yr field experiment where grassland plant
      communities were subjected to above- and belowground insect herbivory with and
      without N addition, in a full-factorial design. We found that herbivory modified
      plant community responses to N addition. Aboveground herbivory decreased
      aboveground plant community biomass by 21%, but only at elevated N. When
      combined, above- and belowground herbivory had a stronger negative effect on
      plant community biomass at ambient N (11% decrease) than at elevated N (4%
      decrease). In addition, herbivory shifted the functional composition of the plant
      community, and the magnitude of the shifts depended on the N level. The N and
      herbivory treatments synergistically conferred a competitive advantage to forbs,
      which benefited when both herbivory types were present at elevated N. Evenness
      among the plant species groups increased when aboveground herbivory was present,
      but N addition attenuated this increase. Our results demonstrate that a deeper
      understanding of how plant-herbivore interactions above and below ground shape
      the composition of a plant community is crucial for making reliable predictions
      about the ecological consequences of global change.

PMID- 27870013
TI  - Short-term and long-term effects of childhood cancer on income from employment
      and employment status: A national cohort study in Sweden.
AB  - BACKGROUND: There is insufficient knowledge regarding the economic impact of
      childhood cancer on parents. The objectives of the current study were to
      investigate the short-term and long-term effects of childhood cancer on mothers'
      and fathers' income from employment and employment status. METHODS: The study
      sample consisted of the parents of children diagnosed with cancer from 2004 to
      2009 in Sweden (3626 parents of 1899 children). Annual register data concerning
      income from employment and employment status (employed/not employed) were
      retrieved from the Longitudinal Integration Database for Health Insurance and
      Labor Market Studies. Using generalized linear models, the mean income from
      employment and employment status were compared with a matched control cohort of
      34,874 parents sampled from the general population. RESULTS: Parents' income was
      found to decrease significantly after the child's cancer diagnosis. The effect
      was most pronounced for mothers, whose income was reduced for 6 years after
      diagnosis, whereas fathers' income was similar to that of control fathers 3 years
      after the diagnosis. Mothers were more likely to stop working after a child's
      cancer diagnosis compared with controls. No association was found for fathers'
      employment status. Younger age of parents; lower level of education; and, among
      mothers, being born outside of Sweden were found to be associated with more
      adverse effects on income. CONCLUSIONS: Parents' income from employment and
      employment status appear to be adversely affected by having a child with cancer.
      Socioeconomic consequences are not distributed equally: the income of fathers
      appears to catch up after a few years, whereas mothers tend to be disadvantaged
      in their professional life for several years after a child's cancer diagnosis.
      Cancer 2017;123:1238-1248. (c) 2016 American Cancer Society.

PMID- 27870014
TI  - Sensitivity of coral recruitment to subtle shifts in early community succession.
AB  - Community succession following disturbance depends on positive and negative
      interactions, the strength of which change along environmental gradients. To
      investigate how early succession affects coral reef recovery, we conducted an 18
      month experiment in Palau, using recruitment tiles and herbivore exclusion cages.
      One set of reefs has higher wave exposure and had previously undergone a phase
      shift to macroalgae following a major typhoon, whereas the other set of reefs
      have lower wave exposure and did not undergo a macroalgal phase shift. Similar
      successional trajectories were observed at all sites when herbivores were
      excluded: turf algae dominated early succession, followed by shifts to foliose
      macroalgae and heterotrophic invertebrates. However, trajectories differed in the
      presence of herbivores. At low wave exposure reefs, herbivores promoted coralline
      algae and limited turf and encrusting fleshy algae in crevice microhabitats,
      facilitating optimal coral recruitment. Under medium wave exposure, relatively
      higher but still low coverage of turf and encrusting fleshy algae (15-25%) found
      in crevice microhabitats inhibited coral recruitment, persisting throughout
      multiple recruitment events. Our results indicate that altered interaction
      strength in different wave environments following disturbance can drive subtle
      changes in early succession that cascade to alter secondary succession to coral
      recruitment and system recovery.

PMID- 27870015
TI  - Changing the discourse: we all must be knowledge brokers.

PMID- 27870016
TI  - DMCN 2016 highlights: cerebral palsy epidemiology, communication in autism, and
      more.

PMID- 27870018
TI  - Erratum.

PMID- 27870017
TI  - Atypical haemolytic uraemic syndrome in a patient with sickle cell disease,
      successfully treated with eculizumab.

PMID- 27870019
TI  - Silica uptake and release in live and decaying biomass in a northern hardwood
      forest.
AB  - In terrestrial ecosystems, a large portion (20-80%) of the dissolved Si (DSi) in
      soil solution has passed through vegetation. While the importance of this
      "terrestrial Si filter" is generally accepted, few data exist on the pools and
      fluxes of Si in forest vegetation and the rate of release of Si from decomposing
      plant tissues. We quantified the pools and fluxes of Si through vegetation and
      coarse woody debris (CWD) in a northern hardwood forest ecosystem (Watershed 6,
      W6) at the Hubbard Brook Experimental Forest (HBEF) in New Hampshire, USA.
      Previous work suggested that the decomposition of CWD may have significantly
      contributed to an excess of DSi reported in stream-waters following experimental
      deforestation of Watershed 2 (W2) at the HBEF. We found that woody biomass (wood
      + bark) and foliage account for approximately 65% and 31%, respectively, of the
      total Si in biomass at the HBEF. During the decay of American beech (Fagus
      grandifolia) boles, Si loss tracked the whole-bole mass loss, while yellow birch
      (Betula alleghaniensis) and sugar maple (Acer saccharum) decomposition resulted
      in a preferential Si retention of up to 30% after 16 yr. A power-law model for
      the changes in wood and bark Si concentrations during decomposition, in
      combination with an exponential model for whole-bole mass loss, successfully
      reproduced Si dynamics in decaying boles. Our data suggest that a minimum of 50%
      of the DSi annually produced in the soil of a biogeochemical reference watershed
      (W6) derives from biogenic Si (BSi) dissolution. The major source is fresh
      litter, whereas only ~2% comes from the decay of CWD. Decay of tree boles could
      only account for 9% of the excess DSi release observed following the experimental
      deforestation of W2. Therefore, elevated DSi concentrations after forest
      disturbance are largely derived from other sources (e.g., dissolution of BSi from
      forest floor soils and/or mineral weathering).

PMID- 27870020
TI  - Trophic positioning of meiofauna revealed by stable isotopes and food web
      analyses.
AB  - Despite important advances in the ecology of river food webs, the strength and
      nature of the connection between the meio- and macrofaunal components of the web
      are still debated. Some unresolved issues are the effects of the inclusion of
      meiofaunal links and their temporal variations on the overall river food web
      properties, and the significance of autochthonous and allochthonous material for
      these components. In the present study, we conducted analyses of gut content of
      macro- and meiofauna and stable isotope analyses of meiofauna to examine seasonal
      food webs of a chalk stream. The results of the gut content analyses, confirmed
      by the delta13 C signatures, revealed a seasonal shift from a dependence on
      autochthonous (biofilm) to allochthonous food sources. Here, we demonstrate that
      aggregating basal or meiofaunal species into single categories affects key web
      properties such as web size, links, linkage density, and predator-prey ratios.
      More importantly, seasonal variation in attributes characterized the entire web
      and these changes persist regardless of taxonomic resolution. Furthermore, our
      analyses evidenced discrete variations in delta15 N across the meiofauna
      community with a trophic structure that confirms gut content analyses, placing
      the meiofauna high in the food web. We, therefore, conclude that small-body-sized
      taxa can occur high in dynamic river food webs, questioning assumptions that
      trophic position increases with body size and that webs are static.

PMID- 27870021
TI  - Temperature dependence of predation stress and the nutritional ecology of a
      generalist herbivore.
AB  - Prey at risk of predation may experience stress and respond physiologically by
      altering their metabolic rates. Theory predicts that such physiological changes
      should alter prey nutrient demands from N-rich to C-rich macronutrients and shift
      the balance between maintenance and growth/reproduction. Theory further suggests
      that for ectotherms, temperature stands to exacerbate this stress. Yet, the
      interactive effects of predation stress and temperature stress on diet,
      metabolism, and survival of ectotherms are not well known. This knowledge gap was
      addressed with a laboratory study in which wild juvenile grasshoppers were
      collected, assigned to one of three groups, and raised at three different
      temperatures. All grasshoppers had access to equal quantities of two diets
      composed of opposite carbohydrate : protein ratios. Half of the individuals in
      each temperature group were exposed to predation risk cues from spider predators,
      while the other half were kept in risk free conditions. Grasshoppers consumed
      more carbohydrates when exposed to predation risk, but consumption favored
      greater protein intake as temperature increased. Moreover, the difference in
      carbohydrate intake between risk cue and risk free treatments diminished as
      temperature increased. Furthermore, variability between individual consumption
      patterns both within and between treatments decreased markedly as temperature
      increased, suggesting that higher temperatures promote more consistent individual
      consumption behaviors. Grasshoppers grew faster and larger as temperature
      increased, which translated into higher survival rates at higher temperatures.
      Warmer grasshoppers also did not alter their metabolic rates in response to
      predation risk cues, in contrast to colder grasshoppers. Digestive efficiency
      increased with temperature as well -- further indicating that lower temperatures
      were much more stressful than higher temperatures for grasshoppers. The study
      shows that physiological responses of ectothermic herbivores to predation stress
      are highly plastic and temperature dependent, with higher temperatures promoting
      increased protein intake, growth, development, survival, and digestive efficiency
      relative to colder temperatures. These findings help to reconcile why dietary
      responses (proportion of protein vs. carbohydrate intake) to predation stress may
      vary among different prey taxa studied previously.

PMID- 27870023
TI  - Hierarchical filters determine community assembly of urban species pools.
AB  - The majority of humanity now lives in cities or towns, with this proportion
      expected to continue increasing for the foreseeable future. As novel ecosystems,
      urban areas offer an ideal opportunity to examine multi-scalar processes involved
      in community assembly as well as the role of human activities in modulating
      environmental drivers of biodiversity. Although ecologists have made great
      strides in recent decades at documenting ecological relationships in urban areas,
      much remains unknown, and we still need to identify the major ecological factors,
      aside from habitat loss, behind the persistence or extinction of species and
      guilds of species in cities. Given this paucity of knowledge, there is an
      immediate need to facilitate collaborative, interdisciplinary research on the
      patterns and drivers of biodiversity in cities at multiple spatial scales. In
      this review, we introduce a new conceptual framework for understanding the
      filtering processes that mold diversity of urban floras and faunas. We
      hypothesize that the following hierarchical series of filters influence species
      distributions in cities: (1) regional climatic and biogeographical factors; (2)
      human facilitation; (3) urban form and development history; (4) socioeconomic and
      cultural factors; and (5) species interactions. In addition to these filters,
      life history and functional traits of species are important in determining
      community assembly and act at multiple spatial scales. Using these filters as a
      conceptual framework can help frame future research needed to elucidate processes
      of community assembly in urban areas. Understanding how humans influence
      community structure and processes will aid in the management, design, and
      planning of our cities to best support biodiversity.

PMID- 27870022
TI  - Viability of cyclic populations.
AB  - Theory on viability of small populations is well developed and has led to the
      standard methodology of population viability analysis (PVA) to assess
      vulnerability of single species. However, more complex situations involving
      community dynamics or environmental change violate theoretical assumptions.
      Synthesizing concepts from population, community, and conservation ecology, we
      develop a generic theory on the viability of cyclic populations. The interplay of
      periodic population decline and demography causes varying risk patterns that
      aggregate during cycles and modify the temporal structure of viability. This
      variability is visualized and quantitatively assessed. For two standard viability
      metrics that summarize immediate extinction risk and the general long-term
      conditions of populations, we mathematically describe the impact of population
      cycles. Finally, we suggest and demonstrate PVA for cyclic populations that
      respond to, e.g., seasonality, interannual variation, or trophic interactions.
      Our theoretical and methodological advancement opens a route to viability
      analysis in food webs and trophic meta-communities and equips biodiversity
      conservation with a long-missing tool.

PMID- 27870024
TI  - Macroinvertebrate community assembly on deep-sea wood falls in Monterey Bay is
      strongly influenced by wood type.
AB  - Environmental filtering, including the influence of environmental constraints and
      biological interactions on species' survival, is known to significantly affect
      patterns of community assembly in terrestrial ecosystems. However, its role in
      regulating patterns and processes of community assembly in deep-sea environments
      is poorly studied. Here we investigated the role of wood characteristics in the
      assembly of deep-sea wood fall communities. Ten different wood species
      (substrata) that varied in structural complexity were sunk to a depth of 3,100 m
      near Monterey Bay, CA. In total, 28 wood parcels were deployed on the deep-sea
      bed. After 2 yr, the wood parcels were recovered with over 7,000 attached or
      colonizing macroinvertebrates. All macroinvertebrates were identified to the
      lowest taxonomic level possible, and included several undescribed species.
      Diversity indices and multivariate analyses of variance detected significant
      variation in the colonizing community assemblages among different wood substrata.
      Structural complexity seemed to be the primary factor altering community
      composition between wood substrata. For example, wood-boring clams were most
      abundant on solid logs, while small arthropods and limpets were more abundant on
      bundles of branches that provided more surface area and small, protected spaces
      to occupy. Other factors such as chemical defenses, the presence of bark, and
      wood hardness likely also played a role. Our finding that characteristics of
      woody debris entering the marine realm can have significant effects on community
      assembly supports the notion of ecological and perhaps evolutionarily significant
      links between land and sea.

PMID- 27870025
TI  - Elephants in the understory: opposing direct and indirect effects of consumption
      and ecosystem engineering by megaherbivores.
AB  - Positive indirect effects of consumers on their resources can stabilize food webs
      by preventing overexploitation, but the coupling of trophic and non-trophic
      interactions remains poorly integrated into our understanding of community
      dynamics. Elephants engineer African savanna ecosystems by toppling trees and
      breaking branches, and although their negative effects on trees are well
      documented, their effects on small-statured plants remain poorly understood.
      Using data on 117 understory plant taxa collected over 7 yr within 36 1-ha
      experimental plots in a semi-arid Kenyan savanna, we measured the strength and
      direction of elephant impacts on understory vegetation. We found that elephants
      had neutral effects on most (83-89%) species, with a similar frequency of
      positive and negative responses among the remainder. Overall, estimated
      understory biomass was 5-14% greater in the presence of elephants across a range
      of rainfall levels. Whereas direct consumption likely accounts for the negative
      effects, positive effects are presumably indirect. We hypothesized that elephants
      create associational refuges for understory plants by damaging tree canopies in
      ways that physically inhibit feeding by other large herbivores. As predicted,
      understory biomass and species richness beneath elephant-damaged trees were 55%
      and 21% greater, respectively, than under undamaged trees. Experimentally
      simulated elephant damage increased understory biomass by 37% and species
      richness by 49% after 1 yr. Conversely, experimentally removing elephant damaged
      branches decreased understory biomass by 39% and richness by 30% relative to sham
      manipulated trees. Camera-trap surveys revealed that elephant damage reduced the
      frequency of herbivory by 71%, whereas we detected no significant effect of
      damage on temperature, light, or soil moisture. We conclude that elephants
      locally facilitate understory plants by creating refuges from herbivory, which
      countervails the direct negative effects of consumption and enhances larger-scale
      biomass and diversity by promoting the persistence of rare and palatable species.
      Our results offer a counterpoint to concerns about the deleterious impacts of
      elephant "overpopulation" that should be considered in debates over wildlife
      management in African protected areas: understory species comprise the bulk of
      savanna plant biodiversity, and their responses to elephants are buffered by the
      interplay of opposing consumptive and non-consumptive interactions.

PMID- 27870026
TI  - Global associations between birds and vane-dwelling feather mites.
AB  - Understanding host-symbiont networks is a major question in evolutionary ecology.
      Birds host a great diversity of endo- and ectosymbiotic organisms, with feather
      mites (Arachnida: Acariformes: Analgoidea, Pterolichoidea) being among the most
      diverse of avian symbionts. A global approach to the ecology and evolution of
      bird-feather-mite associations has been hampered because of the absence of a
      centralized data repository. Here we present the most extensive data set of
      associations between feather mites and birds. Data include 12 036 records of 1887
      feather mite species located on the flight feathers of 2234 bird species from 147
      countries. Feather mites typically located inside quills, on the skin, or on
      downy body feathers are not included. Data were extracted from 493 published
      sources dating from 1882 to 2015. Data exploration shows that although most
      continents and bird families are represented, most bird species remain unexplored
      for feather mites. Nevertheless, this is the most comprehensive data set
      available for enabling global macroecological analyses of feather mites and their
      hosts, such as ecological network analyses. This metadata file outlines the
      structure of these data and provides primary references for all records used.

PMID- 27870027
TI  - Hunting on a hot day: effects of temperature on interactions between African wild
      dogs and their prey.
AB  - As global temperatures increase, interactions between species are affected by
      changes in distribution, abundance and phenology, but also by changes in
      behavior. The heat dissipation limitation hypothesis suggests that the ability to
      dissipate heat commonly limits the activity of endotherms, a problem that should
      be particularly acute for cursorial predators and their prey in equatorial
      ecosystems. Allometric relationships suggest that heat dissipation should be a
      stronger constraint for larger species, so that (smaller) predators should be
      less affected than (larger) prey. We used data from 266 complete days of direct
      observation of African wild dogs (Lycaon pictus) in five packs over a period of 2
      yr to test how deviations of temperature from that expected for the time of day
      affected eight measures of hunting effort and success. We found that higher
      temperatures disadvantaged the prey of wild dogs more than the dogs themselves,
      with increased hunting success and shorter pursuits on warmer days. Broadly, our
      results demonstrate that effects of temperature on behavior can alter
      interactions between species, exacerbating or offsetting the direct effects of
      climate change.

PMID- 27870029
TI  - Native-exotic richness relationships: a biogeographic approach using turnover in
      island plant populations.
AB  - Spatial variation in exotic species richness is often correlated with native
      species richness, for reasons that are poorly understood. To better understand
      the mechanisms underpinning native-exotic richness relationships, I quantified
      the colonization and extinction of 18 exotic and 16 native plant species on 39
      small islands located off the coast of New Zealand for 8 consecutive yr. Results
      revealed a positive native-exotic richness relationship, which could be explained
      by similar demographic responses of native and exotic species to island area.
      However, native and exotic species showed subtle differences in their response to
      other island attributes. Turnover in native species declined with island
      isolation, whereas turnover in exotic species increased with the exposure of
      islands to ocean-borne disturbances. Overall results illustrate how long-term
      observations of species turnover can be used to better understand the mechanisms
      underpinning native-exotic richness relationships, and demonstrate that large,
      exposed islands can be especially susceptible to invasions by exotic species.

PMID- 27870028
TI  - Chronic warming stimulates growth of marsh grasses more than mangroves in a
      coastal wetland ecotone.
AB  - Increasing temperatures and a reduction in the frequency and severity of freezing
      events have been linked to species distribution shifts. Across the globe,
      mangrove ranges are expanding toward higher latitudes, likely due to diminishing
      frequency of freezing events associated with climate change. Continued warming
      will alter coastal wetland plant dynamics both above- and belowground,
      potentially altering plant capacity to keep up with sea level rise. We conducted
      an in situ warming experiment, in northeast Florida, to determine how increased
      temperature (+2 degrees C) influences co-occurring mangrove and salt marsh
      plants. Warming was achieved using passive warming with three treatment levels
      (ambient, shade control, warmed). Avicennia germinans, the black mangrove,
      exhibited no differences in growth or height due to experimental warming, but
      displayed a warming-induced increase in leaf production (48%). Surprisingly,
      Distichlis spicata, the dominant salt marsh grass, increased in biomass (53% in
      2013 and 70% in 2014), density (41%) and height (18%) with warming during summer
      months. Warming decreased plant root mass at depth and changed abundances of
      anaerobic bacterial taxa. Even while the poleward shift of mangroves is clearly
      controlled by the occurrences of severe freezes, chronic warming between these
      freeze events may slow the progression of mangrove dominance within ecotones.

PMID- 27870030
TI  - Fish introductions and light modulate food web fluxes in tropical streams: a
      whole-ecosystem experimental approach.
AB  - Decades of ecological study have demonstrated the importance of top-down and
      bottom-up controls on food webs, yet few studies within this context have
      quantified the magnitude of energy and material fluxes at the whole-ecosystem
      scale. We examined top-down and bottom-up effects on food web fluxes using a
      field experiment that manipulated the presence of a consumer, the Trinidadian
      guppy Poecilia reticulata, and the production of basal resources by thinning the
      riparian forest canopy to increase incident light. To gauge the effects of these
      reach-scale manipulations on food web fluxes, we used a nitrogen (15 N) stable
      isotope tracer to compare basal resource treatments (thinned canopy vs. control)
      and consumer treatments (guppy introduction vs. control). The thinned canopy
      stream had higher primary production than the natural canopy control, leading to
      increased N fluxes to invertebrates that feed on benthic biofilms (grazers), fine
      benthic organic matter (collector-gatherers), and organic particles suspended in
      the water column (filter feeders). Stream reaches with guppies also had higher
      primary productivity and higher N fluxes to grazers and filter feeders. In
      contrast, N fluxes to collector-gatherers were reduced in guppy introduction
      reaches relative to upstream controls. N fluxes to leaf-shredding invertebrates,
      predatory invertebrates, and the other fish species present (Hart's killifish,
      Anablepsoides hartii) did not differ across light or guppy treatments, suggesting
      that effects on detritus-based linkages and upper trophic levels were not as
      strong. Effect sizes of guppy and canopy treatments on N flux rates were similar
      for most taxa, though guppy effects were the strongest for filter feeding
      invertebrates while canopy effects were the strongest for collector-gatherer
      invertebrates. Combined, these results extend previous knowledge about top-down
      and bottom-up controls on ecosystems by providing experimental, reach-scale
      evidence that both pathways can act simultaneously and have equally strong
      influence on nutrient fluxes from inorganic pools through primary consumers.

PMID- 27870032
TI  - Warm vegetarians? Heat waves and diet shifts in tadpoles.
AB  - Temperature can play an important role in determining the feeding preferences of
      ectotherms. In light of the warmer temperatures arising with the current climatic
      changes, omnivorous ectotherms may perform diet shifts toward higher herbivory to
      optimize energetic intake. Such diet shifts may also occur during heat waves,
      which are projected to become more frequent, intense, and longer lasting in the
      future. Here, we investigated how heat waves of different duration affect feeding
      preferences in omnivorous anuran tadpoles and how these choices affect larval
      life history. In laboratory experiments, we fed tadpoles of three species on
      animal, plant, or mixed diet and exposed them to short heat waves (similar to the
      heat waves these species experience currently) or long heat waves (predicted to
      increase under climate change). We estimated the dietary choices of tadpoles fed
      on the mixed diet using stable isotopes and recorded tadpole survival and growth,
      larval period, and mass at metamorphosis. Tadpole feeding preferences were
      associated with their thermal background, with herbivory increasing with breeding
      temperature in nature. Patterns in survival, growth, and development generally
      support decreased efficiency of carnivorous diets and increased efficiency or
      higher relative quality of herbivorous diets at higher temperatures. All three
      species increased herbivory in at least one of the heat wave treatments, but the
      responses varied among species. Diet shifts toward higher herbivory were
      maladaptive in one species, but beneficial in the other two. Higher herbivory in
      omnivorous ectotherms under warmer temperatures may impact species differently
      and further contribute to changes in the structure and function of freshwater
      environments.

PMID- 27870031
TI  - Top-down limitation of lemmings revealed by experimental reduction of predators.
AB  - It is generally recognized that delayed density-dependence is responsible for
      cyclic population dynamics. However, it is still uncertain whether a single
      factor can explain why some rodent populations fluctuate according to a 3-4 yr
      periodicity. There is increasing evidence that predation may play a role in
      lemming population cycles, although this effect may vary seasonally. To address
      this issue, we conducted an experiment where we built a large exclosure (9 ha) to
      protect brown lemmings (Lemmus trimucronatus) from avian and terrestrial
      predators. We tested the hypothesis that predation is a limiting factor for
      lemmings by measuring the demographic consequences of a predator reduction during
      the growth and peak phases of the cycle. We assessed summer (capture-mark
      recapture methods) and winter (winter nest sampling) lemming demography on two
      grids located on Bylot Island, Nunavut, Canada from 2008 to 2015. The predator
      exclosure became fully effective in July 2013, allowing us to compare demography
      between the control and experimental grids before and during the treatment.
      Lemming abundance, survival and proportion of juveniles were similar between the
      two grids before the treatment. During the predator-reduction period, summer
      densities were on average 1.9* higher inside the experimental grid than the
      control and this effect was greatest for adult females and juveniles (densities
      2.4* and 3.4* higher, respectively). Summer survival was 1.6* higher on the
      experimental grid than the control whereas body mass and proportion of juveniles
      were also slightly higher. Winter nest densities remained high inside the
      predator reduction grid following high summer abundance, but declined on the
      control grid. These results confirm that predation limits lemming population
      growth during the summer due to its negative impact on survival. However, it is
      possible that in winter, predation may interact with other factors affecting
      reproduction and ultimately population cycles.

PMID- 27870033
TI  - Ode to Ehrlich and Raven or how herbivorous insects might drive plant speciation.
AB  - Fifty years ago, Ehrlich and Raven proposed that insect herbivores have driven
      much of plant speciation, particularly at tropical latitudes. There have been no
      explicit tests of their hypotheses. Indeed there were no proposed mechanisms
      either at the time or since by which herbivores might generate new plant species.
      Here we outline two main classes of mechanisms, prezygotic and postzygotic, with
      a number of scenarios in each by which herbivore-driven changes in host plant
      secondary chemistry might lead to new plant lineage production. The former apply
      mainly to a sympatric model of speciation while the latter apply to a parapatric
      or allopatric model. Our review suggests that the steps of each mechanism are
      known to occur individually in many different systems, but no scenario has been
      thoroughly investigated in any one system. Nevertheless, studies of Dalechampia
      and its herbivores and pollinators, and patterns of defense tradeoffs in trees on
      different soil types in the Peruvian Amazon provide evidence consistent with the
      original hypotheses of Ehrlich and Raven. For herbivores to drive sympatric
      speciation, our findings suggest that interactions with both their herbivores and
      their pollinators should be considered. In contrast, herbivores may drive
      speciation allopatrically without any influence by pollinators. Finally, there is
      evidence that these mechanisms are more likely to occur at low latitudes and thus
      more likely to produce new species in the tropics. The mechanisms we outline
      provide a predictive framework for further study of the general role that
      herbivores play in diversification of their host plants.

PMID- 27870034
TI  - Measuring partner choice in plant-pollinator networks: using null models to
      separate rewiring and fidelity from chance.
AB  - Recent studies of mutualistic networks show that interactions between partners
      change across years. Both biological mechanisms and chance could drive these
      patterns, but the relative importance of these factors has not been separated. We
      established a field experiment consisting of 102 monospecific plots of 17 native
      plant species, from which we collected 6713 specimens of 52 bee species over four
      years. We used these data and a null model to determine whether bee species'
      foraging choices varied more or less over time beyond the variation expected by
      chance. Thus we provide the first quantitative definition of rewiring and
      fidelity as these terms are used in the literature on interaction networks. All
      52 bee species varied in plant partner choice across years, but for 27 species
      this variation was indistinguishable from random partner choice. Another 11
      species showed rewiring, varying more across years than expected by chance, while
      14 species showed fidelity, indicating that they both prefer certain plant
      species and are consistent in those preferences across years. Our study shows
      that rewiring and fidelity both exist in mutualist networks, but that once
      sampling effects have been accounted for, they are less common than has been
      reported in the ecological literature.

PMID- 27870035
TI  - Large, connected floodplain forests prone to flooding best sustain plant
      diversity.
AB  - Dams, levees, and water withdrawals disrupt hydrologic regimes and associated
      floodplain forests. Because these forests are also responding to changes in land
      use, species invasions, and climate change, the relative effects of these factors
      are hard to disentangle. Most studies of floodplain forests lack historic data,
      requiring us to rely on recent data or contemporary spatial relationships to
      these drivers to infer those causes of vegetation dynamics. Here, we use survey
      data from the 1950s to reconstruct plant community changes across 40 floodplain
      forests in Wisconsin. We applied two partial least squares regression (PLS)
      models to evaluate how current site and landscape scale conditions and changes in
      these conditions since the 1950s influence contemporary patterns of community
      diversity and composition. Local site variables were among the most important in
      explaining current composition metrics and their changes, but historic landscape
      variables and changes in these were also important. Current local diversity
      (alpha) was the highest at sites prone to frequent flooding, even at sites in
      fragmented landscapes. Sites along sinuous rivers in large watershed areas with
      more contiguous forest had the highest abundance of wetland indicator plants in
      the re-survey and had the largest increases in alpha diversity since the 1950s,
      despite having the highest presence of exotic species then. These same sites have
      converged in composition, reflecting increases in wetland indicator plants and
      common native species. These patterns of increasing alpha diversity coupled with
      declines in community distinctiveness are uncommon among long-term studies.
      Increases in wetland plants may indicate that sites have become wetter with
      hydrologic changes, but these increases may also reflect improved colonization
      and establishment processes involving a robust regional pool of generalist
      wetland taxa. Woody and exotic plants typical of upland forests increased at
      rarely flooded sites in fragmented and urbanizing landscapes, indicating shifts
      towards a later-successional conditions and a dampened disturbance regime. This
      has reduced local species diversity and increased regional distinctness at some
      sites. As hydrologic connections appear to best maintain native species diversity
      and composition, even in fragmented landscapes, managers should seek to recreate
      these whenever feasible.

PMID- 27870036
TI  - Seedling performance covaries with dormancy thresholds: maintaining cryptic seed
      heteromorphism in a fire-prone system.
AB  - The production of morphologically different seeds or fruits by the same
      individual plant is known as seed heteromorphism. Such variation is expected to
      be selected for in disturbance-prone environments to allow germination into
      inherently variable regeneration niches. However, there are few demonstrations
      that heteromorphic seed characteristics should be favored by selection or how
      they may be maintained. In fire-prone ecosystems, seed heteromorphism is found in
      the temperatures needed to break physical dormancy, with seeds responding to high
      or low temperatures, ensuring emergence under variable fire-regime-related soil
      heating. Because of the relationship between dormancy-breaking temperature
      thresholds and fire severity, we hypothesize that different post-fire resource
      conditions have selected for covarying seedling traits, which contribute to
      maintenance of such heteromorphism. Seeds with low thresholds emerge into
      competitive conditions, either after low-severity fire or in vegetation gaps, and
      are therefore likely to experience selection for seedling characteristics that
      make them good competitors. On the other hand, high-temperature-threshold seeds
      would emerge into less competitive environments, indicative of stand-clearing
      high-severity fires, and would not experience the same selective forces. We
      identified high and low-threshold seed morphs via dormancy-breaking heat
      treatments and germination trials for two study species and compared seed mass
      and other morphological characteristics between morphs. We then grew seedlings
      from the two different morphs, with and without competition, and measured growth
      and biomass allocation as indicators of seedling performance. Seedlings from low
      threshold seeds of both species performed better than their high-threshold
      counterparts, growing more quickly under competitive conditions, confirming that
      different performance can result from this seed characteristic. Seed mass or
      appearance did not differ between morphs, indicating that dormancy-breaking
      temperature threshold variation is a form of cryptic heteromorphism. The
      potential shown for the selective influence of different post-fire environmental
      conditions on seedling performance provides evidence of a mechanism for the
      maintenance of heteromorphic variation in dormancy-breaking temperature
      thresholds.

PMID- 27870037
TI  - Chronic wasting disease in white-tailed deer: infection, mortality, and
      implications for heterogeneous transmission.
AB  - Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting free
      ranging and captive cervids that now occurs in 24 U.S. states and two Canadian
      provinces. Despite the potential threat of CWD to deer populations, little is
      known about the rates of infection and mortality caused by this disease. We used
      epidemiological models to estimate the force of infection and disease-associated
      mortality for white-tailed deer in the Wisconsin and Illinois CWD outbreaks.
      Models were based on age-prevalence data corrected for bias in aging deer using
      the tooth wear and replacement method. Both male and female deer in the Illinois
      outbreak had higher corrected age-specific prevalence with slightly higher female
      infection than deer in the Wisconsin outbreak. Corrected ages produced more
      complex models with different infection and mortality parameters than those based
      on apparent prevalence. We found that adult male deer have a more than threefold
      higher risk of CWD infection than female deer. Males also had higher disease
      mortality than female deer. As a result, CWD prevalence was twofold higher in
      adult males than females. We also evaluated the potential impacts of alternative
      contact structures on transmission dynamics in Wisconsin deer. Results suggested
      that transmission of CWD among male deer during the nonbreeding season may be a
      potential mechanism for producing higher rates of infection and prevalence
      characteristically found in males. However, alternatives based on high
      environmental transmission and transmission from females to males during the
      breeding season may also play a role.

PMID- 27870039
TI  - Recent publications of interest.

PMID- 27870038
TI  - Variation in stability of elk and red deer populations with abiotic and biotic
      factors at the species-distribution scale.
AB  - Stability in population dynamics is an emergent property of the interaction
      between direct and delayed density dependence, the strengths of which vary with
      environmental covariates. Analysis of variation across populations in the
      strength of direct and delayed density dependence can reveal variation in
      stability properties of populations at the species level. We examined the
      stability properties of 22 elk/red deer populations in a two-stage analysis.
      First, we estimated direct and delayed density dependence applying an AR(2) model
      in a Bayesian hierarchical framework. Second, we plotted the coefficients of
      direct and delayed density dependence in the Royama parameter plane. We then used
      a hierarchical approach to test the significance of environmental covariates of
      direct and delayed density dependence. Three populations exhibited highly stable
      and convergent dynamics with strong direct, and weak delayed, density dependence.
      The remaining 19 populations exhibited more complex dynamics characterized by
      multi-annual fluctuations. Most (15 of 19) of these exhibited a combination of
      weak to moderate direct and delayed density dependence. Best-fit models included
      environmental covariates in 17 populations (77% of the total). Of these,
      interannual variation in growing-season primary productivity and interannual
      variation in winter temperature were the most common, performing as the best-fit
      covariate in six and five populations, respectively. Interannual variation in
      growing-season primary productivity was associated with the weakest combination
      of direct and delayed density dependence, while interannual variation in winter
      temperature was associated with the strongest combination of direct and delayed
      density dependence. These results accord with a classic theoretical prediction
      that environmental variability should weaken population stability. They
      furthermore suggest that two forms of environmental variability, one related to
      forage resources and the other related to abiotic conditions, both reduce
      stability, but in opposing fashion: one through weakened direct density
      dependence and the other through strengthened delayed density dependence.
      Importantly, however, no single abiotic or biotic environmental factor emerged as
      generally predictive of the strengths of direct or delayed density dependence,
      nor of the stability properties emerging from their interaction. Our results
      emphasize the challenges inherent to ascribing primacy to drivers of such
      parameters at the species level and distribution scale.

PMID- 27870041
TI  - Trophic interactions may reverse the demographic consequences of inbreeding.
AB  - Extinctions have no simple determinism, but rather result from complex interplays
      between environmental factors and demographic-genetic feedback that occur at
      small population size. Inbreeding depression has been assumed to be a major
      trigger of extinction vortices, yet very few models have studied its consequences
      in dynamic populations with realistic population structure. Here we investigate
      the impact of Complementary Sex Determination (CSD) on extinction in parasitoid
      wasps and other insects of the order Hymenoptera. CSD is believed to induce
      enough inbreeding depression to doom simple small populations to extinction, but
      we suggest that in parasitoids CSD may have the opposite effect. Using a
      theoretical model combining the genetics of CSD and the population dynamics of
      host-parasitoid systems, we show that CSD can reduce the risk of parasitoid
      extinction by reducing fluctuations in population size. Our result suggests that
      inbreeding depression is not always a threat to population survival, and that
      considering trophic interactions may reverse some pervasive hypotheses on its
      demographic impact.

PMID- 27870040
TI  - Geographic dialects in volatile communication between sagebrush individuals.
AB  - Plants respond to volatile cues emitted by damaged neighbors to increase their
      defenses against herbivores. We examined whether plants communicated more
      effectively with local neighbors than distant neighbors in a reciprocal
      experiment at two sites. Three branches on focal plants were incubated with air
      from (1) a control, (2) an experimentally clipped "foreign" plant from 230 km
      away, or (3) an experimentally clipped "local" plant from the same population as
      the focal plant. Branches incubated with air from the controls experienced 50-80%
      more leaf damage than those receiving air from experimentally clipped plants. Of
      more interest, branches receiving volatiles from experimentally clipped "local"
      plants received 50-65% of the leaf damage as those receiving volatiles from
      experimentally clipped "foreign" plants. Sabinyl compounds and related terpinenes
      were found to differ consistently for plants from southern and northern sites.
      These results indicate that cues vary geographically in their effectiveness and
      suggest that sagebrush responds more strongly to local than foreign dialects.

PMID- 27870042
TI  - Differential foraging preferences on seed size by rodents result in higher
      dispersal success of medium-sized seeds.
AB  - Rodent preference for scatter-hoarding large seeds has been widely considered to
      favor the evolution of large seeds. Previous studies supporting this conclusion
      were primarily based on observations at earlier stages of seed dispersal, or on a
      limited sample of successfully established seedlings. Because seed dispersal
      comprises multiple dispersal stages, we hypothesized that differential foraging
      preference on seed size by animal dispersers at different dispersal stages would
      ultimately result in medium-sized seeds having the highest dispersal success
      rates. In this study, by tracking a large number of seeds for 5 yr, we
      investigated the effects of seed size on seed fates from seed removal to seedling
      establishment of a dominant plant Pittosporopsis kerrii (Icacinaceae) dispersed
      by scatter-hoarding rodents in tropical forest in southwest China. We found that
      small seeds had a lower survival rate at the early dispersal stage where more
      small seeds were predated at seed stations and after removal; large seeds had a
      lower survival rate at the late dispersal stage, more large seeds were recovered,
      predated after being cached, or larder-hoarded. Medium-sized seeds experienced
      the highest dispersal success. Our study suggests that differential foraging
      preferences by scatter-hoarding rodents at different stages of seed dispersal
      could result in conflicting selective pressures on seed size and higher dispersal
      success of medium-sized seeds.

PMID- 27870044
TI  - Foliar bacteria and soil fertility mediate seedling performance: a new and
      cryptic dimension of niche differentiation.
AB  - The phyllosphere (comprising the leaf surface and interior) is one of the world's
      largest microbial habitats and is host to an abundant and diverse array of
      bacteria. Nonetheless, the degree to which bacterial communities are benign,
      harmful, or beneficial to plants in situ is unknown. We tested the hypothesis
      that the net effect of reducing bacterial abundance and diversity would vary
      substantially among host species (from harmful to beneficial) and this would be
      strongly mediated by soil resource availability. To test this, we monitored tree
      seedling growth responses to commercial antibiotics among replicated resource
      supply treatments (N, P, K) in a tropical forest in Panama for 29 months. We
      applied either antibiotics or control water to replicated seedlings of five
      common tree species (Alseis blackiana, Desmopsis panamensis, Heisteria concinna,
      Sorocea affinis, and Tetragastris panamensis). These antibiotic treatments
      significantly reduced both the abundance and diversity of bacteria epiphytically
      as well as endophytically. Overall, the effect of antibiotics on performance was
      highly host specific. Applying antibiotics increased growth for three species by
      as much as 49% (Alseis, Heisteria, and Tetragastris), decreased growth for a
      fourth species by nearly 20% (Sorocea), and had no impact on a fifth species
      (Desmopsis). Perhaps more importantly, the degree to which foliar bacteria were
      harmful or not varied with soil resource supply. Specifically, applying
      antibiotics had no effect when potassium was added but increased growth rate by
      almost 40% in the absence of potassium. Alternatively, phosphorus enrichment
      caused the effect of bacteria to switch from being primarily beneficial to
      harmful or vice versa, but this depended entirely on the presence or absence of
      nitrogen enrichment (i.e., important and significant interactions). Our results
      are the first to demonstrate that the net effect of reducing the abundance and
      diversity of bacteria can have very strong positive and negative effects on
      seedling performance. Moreover, these effects were clearly mediated by soil
      resource availability. Though speculative, we suggest that foliar bacteria may
      interact with soil fertility to comprise an important, yet cryptic dimension of
      niche differentiation, which can have important implications for species
      coexistence.

PMID- 27870043
TI  - Increased seedling establishment via enemy release at the upper elevational range
      limit of sugar maple.
AB  - The enemy release hypothesis is frequently invoked to explain invasion by
      nonnative species, but studies focusing on the influence of enemies on natural
      plant range expansion due to climate change remain scarce. We combined multiple
      approaches to study the influence of plant-enemy interactions on the upper
      elevational range limit of sugar maple (Acer saccharum) in southeastern Quebec,
      Canada, where a previous study had demonstrated intense seed predation just
      beyond the range limit. Consistent with the hypothesis of release from natural
      enemies at the range limit, data from both natural patterns of regeneration and
      from seed and seedling transplant experiments showed higher seedling densities at
      the range edge than in the core of the species' distribution. A growth chamber
      experiment manipulating soil origin and temperature indicated that this so-called
      "happy edge" was not likely caused by temperature (i.e., the possibility that
      climate warming has made high elevation temperatures optimal for sugar maple) or
      by abiotic soil factors that vary along the elevational gradient. Finally, an
      insect-herbivore-exclusion experiment showed that insect herbivory was a major
      cause of seedling mortality in the core of sugar maple's distribution, whereas
      seedlings transplanted at or beyond the range edge experienced minimal herbivory
      (i.e., enemy release). Insect herbivory did not completely explain the high
      levels of seedling mortality in the core of the species' distribution, suggesting
      that seedlings at or beyond the range edge may also experience release from
      pathogens. In sum, while some effects of enemies are magnified beyond range edges
      (e.g., seed predation), others are dampened at and beyond the range edge (e.g.,
      insect herbivory), such that understanding the net outcome of different biotic
      interactions within, at and beyond the edge of distribution is critical to
      predicting species' responses to global change.

PMID- 27870045
TI  - Unprecedented remote sensing data over King and Rim megafires in the Sierra
      Nevada Mountains of California.
AB  - Megafires have lasting social, ecological, and economic impacts and are
      increasing in the western contiguous United States. Because of their infrequent
      nature, there is a limited sample of megafires to investigate their unique
      behavior, drivers, and relationship to forest management practices. One approach
      is to characterize critical information pre-, during, and post-fire using remote
      sensing. In August 2013, the Rim Fire burned 104,131 ha and in September 2014,
      the King Fire burned 39,545 ha. Both fires occurred in California's Sierra
      Nevada. The areas burned by these fires were fortuitously surveyed by airborne
      campaigns, which provided the most recent remote sensing technologies not
      currently available from satellite. Technologies include an imaging spectrometer
      spanning the visible to shortwave infrared (0.38-2.5 MUm), a multispectral, high
      spatial resolution thermal infrared (3.5-13 MUm) spectroradiometer, and Light
      Detection and Ranging that provide spatial resolutions of pixels from 1 * 1 m to
      35 * 35 m. Because of the unique information inherently derived from these
      technologies before the fires, the areas were subsequently surveyed after the
      fires. We processed and provide free dissemination of these airborne datasets as
      products of surface reflectance, spectral metrics and forest structural metrics (
      http://dx.doi.org/10.3334/ORNLDAAC/1288). These data products provide a unique
      opportunity to study relationships among and between remote sensing observations
      and fuel and fire characteristics (e.g., fuel type, condition, structure, and
      fire severity). The novelty of these data is not only in the unprecedented types
      of information available from them before, during, and after two megafires, but
      also in the synergistic use of multiple state of the art technologies for
      characterizing the environment. The synergy of these data can provide novel
      information that can improve maps of fuel type, structure, abundance, and
      condition that may improve predictions of megafire behavior and effects, thus
      aiding management before, during, and after such events. Key questions that these
      data could address include: What drives, extinguishes, and results from
      megafires? How does megafire behavior relate to fire and fuel management? How
      does the size and severity of a megafire affect the ecological recovery of the
      system?

PMID- 27870046
TI  - Naive tadpoles do not recognize recent invasive predatory fishes as dangerous.
AB  - Invasive alien predators (IAP) are spreading on a global scale-often with
      devastating ecological effects. One reason for their success may be that prey
      species fail to recognize them due to a lack of co-evolutionary history. We
      performed a comprehensive test of this "prey naivete" hypothesis using a novel
      approach: we tested whether predator-naive tadpoles of the agile frog (Rana
      dalmatina) display antipredator behavior upon encountering chemical cues produced
      by native, invasive (established or recent) or allopatric fishes (four
      perciforms, four siluriforms, and two cypriniforms). We studied the influence of
      population origin on predator-detection ability by presenting chemical cues to
      predator-naive tadpoles that originated from fishless hill-ponds or fish-infested
      floodplain populations. Before trials, we fed fishes with tadpoles or an
      alternative food to test whether direct chemical cues from the predator's diet
      influences the tadpoles' recognition of potential predators. Tadpoles reduced
      their activity upon exposure to cues from native and long-established invasive
      perciforms, but not in response to recent invaders, allopatric predators, or to
      any siluriforms. Also, predators that were previously fed with tadpoles did not
      universally induce behavioral defensedefenses upon first encounter. Finally,
      tadpoles originating from isolated hill-ponds exhibited higher baseline activity
      and responded in weaker fashion than their conspecifics from floodplain
      populations, which co-exist with predatory fishes. Our results indicate that
      tadpoles may be vulnerable to invading predatory fishes due to their inability to
      recognize them as dangerous, though their ability to recognize invasive IAP may
      evolve rapidly, in fewer than 30 generations.

PMID- 27870047
TI  - A keystone ecologist: Robert Treat Paine, 1933-2016.
AB  - Robert T. Paine, who passed away on 13 June 2016, is among the most influential
      people in the history of ecology. Paine was an experimentalist, a theoretician, a
      practitioner, and proponent of the "ecology of place," and a deep believer in the
      importance of natural history to ecological understanding. His scientific legacy
      grew from the discovery of a link between top-down forcing and species diversity,
      a breakthrough that led to the ideas of both keystone species and trophic
      cascades, and to our early understanding of the mosaic nature of biological
      communities, causes of zonation across physical gradients, and the intermediate
      disturbance hypothesis of species diversity. Paine's influence as a mentor was
      equally important to the growth of ecological thinking, natural resource
      conservation, and policy. He served ecology as an Ecological Society of America
      president, an editor of the Society's journals, a member of and contributor to
      the National Academy of Sciences and the National Research Council, and an in
      demand advisor to various state and federal agencies. Paine's broad interests,
      enthusiasm, charisma, and humor deeply affected our lives and the lives of so
      many others.

PMID- 27870048
TI  - Contacts with large, active individuals intensify the predation risk of small
      conspecifics.
AB  - Size variation within a population can influence the structure of ecosystem
      interactions, because ecological performance differs between individuals of
      different sizes. Although the impact of size variation in a predator species on
      the structure of interactions is well understood, our knowledge about how size
      variation in a prey species might modify the interactions between predators and
      prey is very limited. Here, by examining the interactions between predatory
      Hynobius retardatus salamander larvae and their prey, Rana pirica frog tadpoles,
      we investigated how large prey individuals affect the predation mortality of
      small prey conspecifics. First, in an experiment conducted in a field pond in
      which we manipulated the presence of salamanders and large tadpoles (i.e., large
      enough to protect them against salamander predation) with small tadpoles, we
      showed that in the presence of large tadpoles the mortality of small tadpoles
      from salamander predation was increased. On the basis of our observations of the
      activity of individuals, we hypothesized that active large tadpoles caused
      physical disturbances, which in turn caused the small tadpoles to move, and thus
      increased their encounter frequency with the predatory salamanders. To test this
      hypothesis, we conducted a laboratory experiment in small tanks with three
      players (i.e., one salamander as predator, one small tadpole as focal prey, and
      either a small or a large tadpole as the prospective movement inducer). In each
      tank, we manipulated the presence or absence of a movement inducer, and, when
      present, its size (large or small) and access (caged or uncaged) to the focal
      prey. In the presence of a large, uncaged movement inducer, the focal prey was
      more active and suffered from higher predation mortality compared with the other
      treatments, because the large movement inducer (unlike a small movement inducer)
      moved actively and, when uncaged, could stimulate movement of the focal prey
      through direct contact. The results indicated that high activity of large prey
      individuals and the resulting behavioral interactions with small conspecifics via
      direct contact indirectly increased the mortality of the small prey.

PMID- 27870049
TI  - Experimental reduction in interaction intensity strongly affects biotic
      selection.
AB  - The link between biotic interaction intensity and strength of selection is of
      fundamental interest for understanding biotically driven diversification and
      predicting the consequences of environmental change. The strength of selection
      resulting from biotic interactions is determined by the strength of the
      interaction and by the covariance between fitness and the trait under selection.
      When the relationship between trait and absolute fitness is constant, selection
      strength should be a direct function of mean population interaction intensity. To
      test this prediction, we excluded pollinators for intervals of different length
      to induce five levels of pollination intensity within a single plant population.
      Pollen limitation (PL) increased from 0 to 0.77 across treatments, accompanied by
      a fivefold increase in the opportunity for selection. Trait-fitness covariance
      declined with PL for number of flowers, but varied little for other traits.
      Pollinator-mediated selection on plant height, corolla size, and spur length
      increased by 91%, 34%, and 330%, respectively, in the most severely pollen
      limited treatment compared to open-pollinated plants. The results indicate that
      realized biotic selection can be predicted from mean population interaction
      intensity when variation in trait-fitness covariance is limited, and that
      declines in pollination intensity will strongly increase selection on traits
      involved in the interaction.

PMID- 27870050
TI  - A bird pollinator shows positive frequency dependence and constancy of species
      choice in natural plant communities.
AB  - Animal pollinators mediate reproduction of many plant species. Foraging theory
      suggests that animal pollinators exhibit preferences for common plant species in
      natural communities (positive frequency-dependent foraging) and temporary single
      species specialization (flower constancy) during foraging bouts. Positive
      frequency dependence may favor common plant species; flower constancy may enhance
      conspecific pollen transfer particularly in rare plant species. Previous
      experimental studies suggest that avian pollinators are unlikely to exhibit these
      behaviors. We studied foraging behavior of Cape Sugarbirds (Promerops cafer), the
      main avian pollinator of many Protea species, using focal-plant and focal-bird
      sampling, assisted by high-resolution maps of the spatiotemporal distribution of
      Protea individuals and their flowering status. We found that Sugarbird's
      visitation preference increased with species' relative floral abundance, and that
      individual Sugarbirds tended to visit single species in sequence. Flower
      constancy during foraging bouts was significantly higher than expected from
      random plant-animal encounters at the scale of pollinator movements. Positive
      frequency dependence may favor the reproduction of abundant plant species while
      flower constancy may be particularly important for rare plant species. This first
      simultaneous study of both behaviors in a natural plant-pollinator system shows
      that bird pollinators exhibit both types of behavior and, in this way, possibly
      influence plant community structure.

PMID- 27870051
TI  - Chemical similarity and local community assembly in the species rich tropical
      genus Piper.
AB  - Community ecologists have strived to find mechanisms that mediate the assembly of
      natural communities. Recent evidence suggests that natural enemies could play an
      important role in the assembly of hyper-diverse tropical plant systems. Classic
      ecological theory predicts that in order for coexistence to occur, species
      differences must be maximized across biologically important niche dimensions. For
      plant-herbivore interactions, it has been recently suggested that, within a
      particular community, plant species that maximize the difference in chemical
      defense profiles compared to neighboring taxa will have a relative competitive
      advantage. Here we tested the hypothesis that plant chemical diversity can affect
      local community composition in the hyper-diverse genus Piper at a lowland wet
      forest location in Costa Rica. We first characterized the chemical composition of
      27 of the most locally abundant species of Piper. We then tested whether species
      with different chemical compositions were more likely to coexist. Finally, we
      assessed the degree to which Piper phylogenetic relationships are related to
      differences in secondary chemical composition and community assembly. We found
      that, on average, co-occurring species were more likely to differ in chemical
      composition than expected by chance. Contrary to expectations, there was no
      phylogenetic signal for overall secondary chemical composition. In addition we
      found that species in local communities were, on average, more phylogenetically
      closely related than expected by chance, suggesting that functional traits other
      than those measured here also influence local assembly. We propose that selection
      by herbivores for divergent chemistries between closely related species
      facilitates the coexistence of a high diversity of congeneric taxa via apparent
      competition.

PMID- 27870052
TI  - Early warning of critical transitions in biodiversity from compositional
      disorder.
AB  - Global environmental change presents a clear need for improved leading indicators
      of critical transitions, especially those that can be generated from
      compositional data and that work in empirical cases. Ecological theory of
      community dynamics under environmental forcing predicts an early replacement of
      slowly replicating and weakly competitive "canary" species by slowly replicating
      but strongly competitive "keystone" species. Further forcing leads to the
      eventual collapse of the keystone species as they are replaced by weakly
      competitive but fast-replicating "weedy" species in a critical transition to a
      significantly different state. We identify a diagnostic signal of these changes
      in the coefficients of a correlation between compositional disorder and
      biodiversity. Compositional disorder measures unpredictability in the composition
      of a community, while biodiversity measures the amount of species in the
      community. In a stochastic simulation, sequential correlations over time switch
      from positive to negative as keystones prevail over canaries, and back to
      positive with domination of weedy species. The model finds support in empirical
      tests on multi-decadal time series of fossil diatom and chironomid communities
      from lakes in China. The characteristic switch from positive to negative
      correlation coefficients occurs for both communities up to three decades
      preceding a critical transition to a sustained alternate state. This signal is
      robust to unequal time increments that beset the identification of early-warning
      signals from other metrics.

PMID- 27870053
TI  - Absence of net long-term successional facilitation by alder in a boreal Alaska
      floodplain.
AB  - Long-term experiments provide a way to test presumed causes of successional or
      environmentally driven vegetation changes. Early-successional nitrogen (N)-fixing
      plants are widely thought to facilitate productivity and vegetation development
      on N-poor sites, thus accounting for observed vegetation patterns later in
      succession. We tested this facilitative impact on vegetation development in a 23
      yr field experiment on an Interior Alaska (USA) floodplain. On three replicate
      early-successional silt bars, we planted late-successional white spruce (Picea
      glauca) seedlings in the presence and absence of planted seedlings of an early
      successional N-fixing shrub, thinleaf alder (Alnus incana). Alder initially
      facilitated survivorship and growth of white spruce. Within six years, however,
      after canopy closure, alder negatively affected spruce survivorship and growth.
      Our three replicate sites followed different successional trajectories. One site
      was eliminated by erosion and supported no vegetation development during our
      study. The other two sites, which differed in site moisture, diverged in
      vegetation composition. Structural equation modeling (SEM) suggested that, in the
      drier of these two sites, alder inhibited spruce growth directly (presumably by
      competition) and indirectly through effects mediated by competition with other
      woody species. However, at the wetter site, alder had both positive and negative
      effects on spruce growth, with negative effects predominating. Snowshoe hares
      (Lepus americanus) in alder thickets further reduced height growth of spruce in
      the wetter site. We conclude that net effects of alder on white spruce, the late
      successional dominant, were primarily inhibitory and indirect, with the
      mechanisms depending on initial site moisture. Our results highlight the
      importance of long-term research showing that small differences among initial
      replicate sites can cause divergence in successional trajectories, consistent
      with individualistic distributions of species and communities along environmental
      gradients. This divergence was detectable only decades later.

PMID- 27870054
TI  - A plant growth form dataset for the New World.
AB  - This dataset provides growth form classifications for 67,413 vascular plant
      species from North, Central, and South America. The data used to determine growth
      form were compiled from five major integrated sources and two original
      publications: the Botanical Information and Ecology Network (BIEN), the Plant
      Trait Database (TRY), the SALVIAS database, the USDA PLANTS database, Missouri
      Botanical Garden's Tropicos database, Wright (2010), and Boyle (1996). We defined
      nine plant growth forms based on woodiness (woody or non-woody), shoot structure
      (self-supporting or not self-supporting), and root traits (rooted in soil, not
      rooted in soil, parasitic or aquatic): Epiphyte, Liana, Vine, Herb, Shrub, Tree,
      Parasite, or Aquatic. Species with multiple growth form classifications were
      assigned the growth form classification agreed upon by the majority (>2/3) of
      sources. Species with ambiguous or otherwise not interpretable growth form
      assignments were excluded from the final dataset but are made available with the
      original data. Comparisons with independent estimates of species richness for the
      Western hemisphere suggest that our final dataset includes the majority of New
      World vascular plant species. Coverage is likely more complete for temperate than
      for tropical species. In addition, aquatic species are likely under-represented.
      Nonetheless, this dataset represents the largest compilation of plant growth
      forms published to date, and should contribute to new insights across a broad
      range of research in systematics, ecology, biogeography, conservation, and global
      change science.

PMID- 27870055
TI  - Cancer risks after solid organ transplantation and after long-term dialysis.
AB  - Immunosuppression involves an inability to control virus infections and increased
      incidence of virus-associated cancers. Some cancers without known viral etiology
      are also increased, but data on exactly which cancer forms are increased has been
      inconsistent. To provide a reliable and generalizable estimate, with high
      statistical power and long follow-up time, we assessed cancer risks using
      comprehensive, population-based registries in two different countries and from
      two different immunosuppressed patient groups (solid organ transplant recipients
      (OTRs) and long-term dialysis patients (LDPs)). National registries in Denmark
      and Sweden identified 20,804 OTRs and 31,140 LDPs that were followed up using
      national cancer registries. Standardized incidence ratios (SIR) compared to the
      general population were estimated. We found highly similar results, both for the
      two different countries and for the two different immunosuppressed cohorts,
      namely an increased incidence for the following specific cancer forms: Non
      melanoma skin cancer (NMSC), non-Hodgkin's lymphoma and cancers of the lip,
      kidney, larynx and thyroid. The SIR for overall cancer among OTRs was 3.5 [n =
      2,142, 95% CI, 3.4-3.7] in Sweden, 2.9 [n = 1,110, 95% CI, 2.8-3.1] in Denmark
      and 1.6 [n = 1,713, 95% CI, 1.5-1.6] among LDP. The SIR for NMSC among OTRs was
      44.7 [n = 994, 95% CI, 42-47.5] in Sweden and 41.5 [n = 445, 95% CI, 37.8-45.5]
      in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n = 304, 95% CI, 4.7
      5.9]). In summary, an increased SIR for a specific, similar set of cancer forms
      is consistently found among the immunosuppressed. Conceivable explanations
      include surveillance bias and immunosuppression-related susceptibility to viral
      infections.

PMID- 27870056
TI  - Cure of cancer for seven cancer sites in the Flemish Region.
AB  - Cumulative relative survival curves for many cancers reach a plateau several
      years after diagnosis, indicating that the cancer survivor group has reached
      "statistical" cure. Parametric mixture cure model analysis on grouped relative
      survival curves provide an interesting way to determine the proportion of
      statistically cured cases and the mean survival time of the fatal cases in
      particular for population-based cancer registries. Based on the relative survival
      data from the Belgian Cancer Registry, parametric cure models were applied to
      seven cancer sites (cervix, colon, corpus uteri, skin melanoma, pancreas, stomach
      and oesophagus), at the Flemish Regional level for the incidence period 1999
      2011. Statistical cure was observed for the examined cancer sites except for
      oesophageal cancer. The estimated cured proportion ranged from 5.9% [5.7, 6.1]
      for pancreatic cancer to 80.8% [80.5, 81.2] for skin melanoma. Cure results were
      further stratified by gender or age group. Stratified cured proportions were
      higher for females compared to males in colon cancer, stomach cancer, pancreas
      cancer and skin melanoma, which can mainly be attributed to differences in stage
      and age distribution between both sexes. This study demonstrates the
      applicability of cure rate models for the selected cancer sites after 14 years of
      follow-up and presents the first population-based results on the cure of cancer
      in Belgium.

PMID- 27870057
TI  - Investigating the association between perioperative blood transfusions and
      outcomes in children undergoing cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy.
AB  - BACKGROUND AND OBJECTIVES: Studies indicate the perioperative transfusion of red
      blood cells during oncologic surgery may be associated with worse outcomes. In
      this study, we evaluated the impact of red blood cell transfusions on the short-
      and long-term outcomes of children undergoing a major oncologic surgery.
      MATERIALS AND METHODS: A retrospective review of the medical records of children
      <=18 years of age who had undergone cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy was performed. Univariate and multivariate analyses
      were performed to identify factors influencing survival, complications and length
      of stay. RESULTS: Seventy-five children were identified, 80% of whom had received
      a red blood cell transfusion. Children who received a red blood cell transfusion
      had a significantly longer length of stay (P = 0.0003). However, the association
      between red blood cell transfusions and recurrence-free survival (HR: 1.307, 95%
      CI: 0.547-3.124; P = 0.55), overall survival (HR: 1.487, 95% CI: 0.585-3.780; P =
      0.40) or the incidence of major complications (27.8 vs. 0% in non-transfused
      children, P = 0.18) was not statistically significant. CONCLUSION: This
      retrospective study of children undergoing major oncologic surgery did not
      demonstrate a significant association between red blood cell transfusions and
      worse outcomes.

PMID- 27870058
TI  - Iron deficiency and thrombocytosis.
AB  - According to many textbooks, iron deficiency (ID) is associated with reactive
      thrombocytosis. In this study, we aimed to investigate the correlation between
      serum ferritin levels and platelet counts in a large cohort of healthy blood
      donors. We included all whole blood and apheresis donors aged 18 years or older
      with at least one ferritin measurement and one platelet count performed at the
      same visit between 1996 and 2014. A total of 130 345 blood counts and ferritin
      measurements obtained from 22 046 healthy donors were analysed. Overall, no
      correlation between serum ferritin and platelet count was observed (r = -0.03,
      rho = 0.04 for males, and r = 0.01, rho = -0.02 for females, respectively).
      Associations remained clinically negligible after adjusting for age, time since
      previous blood donation, number of donations and restricting the analysis to
      ferritin deciles. In this large, retrospective single-centre study, correlations
      between low ferritin and platelet count in a large and homogeneous cohort of
      healthy donors were negligible. Further studies in patients with more severe
      anaemia and patients with inflammation are warranted.

PMID- 27870060
TI  - Climate drives shifts in grass reproductive phenology across the western USA.
AB  - The capacity of grass species to alter their reproductive timing across space and
      through time can indicate their ability to cope with environmental variability
      and help predict their future performance under climate change. We determined the
      long-term (1895-2013) relationship between flowering times of grass species and
      climate in space and time using herbarium records across ecoregions of the
      western USA. There was widespread concordance of C3 grasses accelerating
      flowering time and general delays for C4 grasses with increasing mean annual
      temperature, with the largest changes for annuals and individuals occurring in
      more northerly, wetter ecoregions. Flowering time was delayed for most grass
      species with increasing mean annual precipitation across space, while phenology
      precipitation relationships through time were more mixed. Our results suggest
      that the phenology of most grass species has the capacity to respond to increases
      in temperature and altered precipitation expected with climate change, but weak
      relationships for some species in time suggest that climate tracking via
      migration or adaptation may be required. Divergence in phenological responses
      among grass functional types, species, and ecoregions suggests that climate
      change will have unequal effects across the western USA.

PMID- 27870059
TI  - Transfer of 13 C between paired Douglas-fir seedlings reveals plant kinship
      effects and uptake of exudates by ectomycorrhizas.
AB  - Processes governing the fixation, partitioning, and mineralization of carbon in
      soils are under increasing scrutiny as we develop a more comprehensive
      understanding of global carbon cycling. Here we examined fixation by Douglas-fir
      seedlings and transfer to associated ectomycorrhizal fungi, soil microbes, and
      full-sibling or nonsibling neighbouring seedlings. Stable isotope probing with
      99% 13 C-CO2 was applied to trace 13 C-labelled photosynthate throughout plants,
      fungi, and soil microbes in an experiment designed to assess the effect of
      relatedness on 13 C transfer between plant pairs. The fixation and transfer of
      the 13 C label to plant, fungal, and soil microbial tissue was examined in
      biomass and phospholipid fatty acids. After a 6 d chase period, c. 26.8% of the
      13 C remaining in the system was translocated below ground. Enrichment was
      proportionally greatest in ectomycorrhizal biomass. The presence of mesh barriers
      (0.5 or 35 MUm) between seedlings did not restrict 13 C transfer. Fungi were the
      primary recipients of 13 C-labelled photosynthate throughout the system,
      representing 60-70% of total 13 C-enriched phospholipids. Full-sibling pairs
      exhibited significantly greater 13 C transfer to recipient roots in two of four
      Douglas-fir families, representing three- and fourfold increases (+ c. 4 MUg
      excess 13 C) compared with nonsibling pairs. The existence of a root/mycorrhizal
      exudation-hyphal uptake pathway was supported.

PMID- 27870061
TI  - Re-annotation, improved large-scale assembly and establishment of a catalogue of
      noncoding loci for the genome of the model brown alga Ectocarpus.
AB  - The genome of the filamentous brown alga Ectocarpus was the first to be
      completely sequenced from within the brown algal group and has served as a key
      reference genome both for this lineage and for the stramenopiles. We present a
      complete structural and functional reannotation of the Ectocarpus genome. The
      large-scale assembly of the Ectocarpus genome was significantly improved and
      genome-wide gene re-annotation using extensive RNA-seq data improved the
      structure of 11 108 existing protein-coding genes and added 2030 new loci. A
      genome-wide analysis of splicing isoforms identified an average of 1.6
      transcripts per locus. A large number of previously undescribed noncoding genes
      were identified and annotated, including 717 loci that produce long noncoding
      RNAs. Conservation of lncRNAs between Ectocarpus and another brown alga, the kelp
      Saccharina japonica, suggests that at least a proportion of these loci serve a
      function. Finally, a large collection of single nucleotide polymorphism-based
      markers was developed for genetic analyses. These resources are available through
      an updated and improved genome database. This study significantly improves the
      utility of the Ectocarpus genome as a high-quality reference for the study of
      many important aspects of brown algal biology and as a reference for genomic
      analyses across the stramenopiles.

PMID- 27870062
TI  - RWP-RK domain-containing transcription factors control cell differentiation
      during female gametophyte development in Arabidopsis.
AB  - The formation of gametes is a prerequisite for any sexually reproducing organism
      in order to complete its life cycle. In plants, female gametes are formed in a
      multicellular tissue, the female gametophyte or embryo sac. Although the events
      leading to the formation of the female gametophyte have been morphologically
      characterized, the molecular control of embryo sac development remains elusive.
      We used single and double mutants as well as cell-specific marker lines to
      characterize a novel class of gene regulators in Arabidopsis thaliana, the RWP-RK
      domain-containing (RKD) transcription factors. Morphological and histological
      analyses were conducted using confocal laser scanning and differential
      interference contrast microscopy. Gene expression and transcriptome analyses were
      performed using quantitative reverse transcription-PCR and RNA sequencing,
      respectively. Our results showed that RKD genes are expressed during distinct
      stages of embryo sac development. Morphological analysis of the mutants revealed
      severe distortions in gametophyte polarity and cell differentiation.
      Transcriptome analysis revealed changes in the expression of several gametophyte
      specific gene families (RKD2 and RKD3) and ovule development-specific genes
      (RKD3), and identified pleiotropic effects on phytohormone pathways (RKD5). Our
      data provide novel insight into the regulatory control of female gametophyte
      development. RKDs are involved in the control of cell differentiation and are
      required for normal gametophytic development.

PMID- 27870063
TI  - The diatom Phaeodactylum tricornutum adjusts nonphotochemical fluorescence
      quenching capacity in response to dynamic light via fine-tuned Lhcx and
      xanthophyll cycle pigment synthesis.
AB  - Diatoms contain a highly flexible capacity to dissipate excessively absorbed
      light by nonphotochemical fluorescence quenching (NPQ) based on the light-induced
      conversion of diadinoxanthin (Dd) into diatoxanthin (Dt) and the presence of Lhcx
      proteins. Their NPQ fine regulation on the molecular level upon a shift to
      dynamic light conditions is unknown. We investigated the regulation of Dd + Dt
      amount, Lhcx gene and protein synthesis and NPQ capacity in the diatom
      Phaeodactylum tricornutum after a change from continuous low light to 3 d of sine
      (SL) or fluctuating (FL) light conditions. Four P. tricornutum strains with
      different NPQ capacities due to different expression of Lhcx1 were included. All
      strains responded to dynamic light comparably, independently of initial NPQ
      capacity. During SL, NPQ capacity was strongly enhanced due to a gradual increase
      of Lhcx2 and Dd + Dt amount. During FL, cells enhanced their NPQ capacity on the
      first day due to increased Dd + Dt, Lhcx2 and Lhcx3; already by the second day
      light acclimation was accomplished. While quenching efficiency of Dt was strongly
      lowered during SL conditions, it remained high throughout the whole FL exposure.
      Our results highlight a more balanced and cost-effective photoacclimation
      strategy of P. tricornutum under FL than under SL conditions.

PMID- 27870064
TI  - The effect of plant water storage on water fluxes within the coupled soil-plant
      system.
AB  - In addition to buffering plants from water stress during severe droughts, plant
      water storage (PWS) alters many features of the spatio-temporal dynamics of water
      movement in the soil-plant system. How PWS impacts water dynamics and drought
      resilience is explored using a multi-layer porous media model. The model
      numerically resolves soil-plant hydrodynamics by coupling them to leaf-level gas
      exchange and soil-root interfacial layers. Novel features of the model are the
      considerations of a coordinated relationship between stomatal aperture variation
      and whole-system hydraulics and of the effects of PWS and nocturnal transpiration
      (Fe,night) on hydraulic redistribution (HR) in the soil. The model results
      suggest that daytime PWS usage and Fe,night generate a residual water potential
      gradient (Deltapsip,night) along the plant vascular system overnight. This
      Deltapsip,night represents a non-negligible competing sink strength that
      diminishes the significance of HR. Considering the co-occurrence of PWS usage and
      HR during a single extended dry-down, a wide range of plant attributes and
      environmental/soil conditions selected to enhance or suppress plant drought
      resilience is discussed. When compared with HR, model calculations suggest that
      increased root water influx into plant conducting-tissues overnight maintains a
      more favorable water status at the leaf, thereby delaying the onset of drought
      stress.

PMID- 27870065
TI  - Photoacclimatory and photoprotective responses to cold versus heat stress in high
      latitude reef corals.
AB  - Corals at the world's southernmost coral reef of Lord Howe Island (LHI)
      experience large temperature and light fluctuations and need to deal with periods
      of cold temperature (<18 degrees C), but few studies have investigated how corals
      are able to cope with these conditions. Our study characterized the response of
      key photophysiological parameters, as well as photoacclimatory and
      photoprotective pigments (chlorophylls, xanthophylls, and beta-carotene), to
      short-term (5-d) cold stress (~15 degrees C; 7 degrees C below control) in three
      LHI coral species hosting distinct Symbiodinium ITS2 types, and compared the
      coral-symbiont response to that under elevated temperature (~29 degrees C; 7
      degrees C above control). Under cold stress, Stylophora sp. hosting Symbiodinium
      C118 showed the strongest effects with regard to losses of photochemical
      performance and symbionts. Pocillopora damicornis hosting Symbiodinium C100/C118
      showed less severe bleaching responses to reduced temperature than to elevated
      temperature, while Porites heronensis hosting Symbiodinium C111* withstood both
      reduced and elevated temperature. Under cold stress, photoprotection in the form
      of xanthophyll de-epoxidation increased in unbleached P. heronensis (by 178%) and
      bleached Stylophora sp. (by 225%), while under heat stress this parameter
      increased in unbleached P. heronensis (by 182%) and in bleached P. damicornis (by
      286%). The xanthophyll pool size was stable in all species at all temperatures.
      Our comparative study demonstrates high variability in the bleaching
      vulnerability of these coral species to low and high thermal extremes and shows
      that this variability is not solely determined by the ability to activate
      xanthophyll de-epoxidation.

PMID- 27870066
TI  - A nonnative and a native fungal plant pathogen similarly stimulate
      ectomycorrhizal development but are perceived differently by a fungal symbiont.
AB  - The effects of plant symbionts on host defence responses against pathogens have
      been extensively documented, but little is known about the impact of pathogens on
      the symbiosis and if such an impact may differ for nonnative and native
      pathogens. Here, this issue was addressed in a study of the model system
      comprising Pinus pinea, its ectomycorrhizal symbiont Tuber borchii, and the
      nonnative and native pathogens Heterobasidion irregulare and Heterobasidion
      annosum, respectively. In a 6-month inoculation experiment and using both in
      planta and gene expression analyses, we tested the hypothesis that H. irregulare
      has greater effects on the symbiosis than H. annosum. Although the two pathogens
      induced the same morphological reaction in the plant-symbiont complex, with
      mycorrhizal density increasing exponentially with pathogen colonization of the
      host, the number of target genes regulated in T. borchii in plants inoculated
      with the native pathogen (i.e. 67% of tested genes) was more than twice that in
      plants inoculated with the nonnative pathogen (i.e. 27% of genes). Although the
      two fungal pathogens did not differentially affect the amount of ectomycorrhizas,
      the fungal symbiont perceived their presence differently. The results may suggest
      that the symbiont has the ability to recognize a self/native and a
      nonself/nonnative pathogen, probably through host plant-mediated signal
      transduction.

PMID- 27870068
TI  - Systematic Review of the Prevalence of Medication Errors Resulting in
      Hospitalization and Death of Nursing Home Residents.
AB  - Medication errors (MEs) result in preventable harm to nursing home (NH) residents
      and pose a significant financial burden. Institutionalized older people are
      particularly vulnerable because of various organizational and individual factors.
      This systematic review reports the prevalence of MEs leading to hospitalization
      and death in NH residents and the factors associated with risk of death and
      hospitalization. A systematic search was conducted of the relevant peer-reviewed
      research published between January 1, 2000, and October 1, 2015, in English,
      French, German, or Spanish examining serious outcomes of MEs in NHs residents.
      Eleven studies met the inclusion criteria and examined three types of MEs: all
      MEs (n = 5), transfer-related MEs (n = 5), and potentially inappropriate
      medications (PIMs) (n = 1). MEs were common, involving 16-27% of residents in
      studies examining all types of MEs and 13-31% of residents in studies examining
      transfer-related MEs, and 75% of residents were prescribed at least one PIM. That
      said, serious effects of MEs were surprisingly low and were reported in only a
      small proportion of errors (0-1% of MEs), with death being rare. Whether MEs
      resulting in serious outcomes are truly infrequent, or are underreported because
      of the difficulty in ascertaining them, remains to be elucidated to assist in
      designing safer systems.

PMID- 27870067
TI  - Informing models through empirical relationships between foliar phosphorus,
      nitrogen and photosynthesis across diverse woody species in tropical forests of
      Panama.
AB  - Our objective was to analyze and summarize data describing photosynthetic
      parameters and foliar nutrient concentrations from tropical forests in Panama to
      inform model representation of phosphorus (P) limitation of tropical forest
      productivity. Gas exchange and nutrient content data were collected from 144
      observations of upper canopy leaves from at least 65 species at two forest sites
      in Panama, differing in species composition, rainfall and soil fertility.
      Photosynthetic parameters were derived from analysis of assimilation rate vs
      internal CO2 concentration curves (A/Ci ), and relationships with foliar nitrogen
      (N) and P content were developed. The relationships between area-based
      photosynthetic parameters and nutrients were of similar strength for N and P and
      robust across diverse species and site conditions. The strongest relationship
      expressed maximum electron transport rate (Jmax ) as a multivariate function of
      both N and P, and this relationship was improved with the inclusion of
      independent data on wood density. Models that estimate photosynthesis from foliar
      N would be improved only modestly by including additional data on foliar P, but
      doing so may increase the capability of models to predict future conditions in P
      limited tropical forests, especially when combined with data on edaphic
      conditions and other environmental drivers.

PMID- 27870070
TI  - What is your diagnosis? Skin scraping from a hellbender.

PMID- 27870069
TI  - Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus
      negative cat.
AB  - A 10-year-old castrated Domestic Short-Haired cat was presented to a primary care
      veterinarian for a wellness examination and laboratory examination for monitoring
      of diabetes mellitus. The CBC revealed marked thrombocytosis, leukopenia and
      macrocytic, normochromic anemia. The cat tested negative for FeLV and feline
      immunodeficiency virus, but was positive for Mycoplasma haemominutum by PCR.
      Hematologic abnormalities were not responsive to therapy, so a repeat CBC and a
      bone marrow aspiration for cytology were performed. Additional blood smear
      findings included anisocytosis with megaloblastic erythroid precursors, large
      platelets, eosinophilic myelocytes and metamyelocytes, and rare unidentified
      blasts. The bone marrow smear was highly cellular, and the cytologic pattern was
      consistent with myelodysplastic syndrome with an erythroid predominance. At that
      time, 15% blasts were present. The cat was treated with a vitamin K2 analog,
      doxycycline, and prednisolone, but without a clinical response. Within 3 months,
      euthanasia was elected due to declining quality of life, and a necropsy was
      performed. Postmortem bone marrow smears were highly cellular and dominated by
      monomorphic blasts of unknown line of origin (52%), persistent marked erythroid
      and megakaryocytic dysplasia, and ineffective erythropoiesis and granulopoiesis.
      Immunohistochemical, immunocytochemical, and cytochemical stains resulted in a
      diagnosis of acute myeloid leukemia of unclassified type. Additional histologic
      findings included mixed hepatitis with trematode infestation and
      lymphoplasmacytic interstitial nephritis with fibrosis. The marked thrombocytosis
      with myelodysplastic syndrome and the FeLV-negative status of this cat were
      unusual. The difficulty in classifying the myelodysplasia and subsequent leukemia
      highlights a need for further reporting and characterization of these types of
      disease.

PMID- 27870072
TI  - Alex J. Zautra (1947-2016).

PMID- 27870071
TI  - Eosinophilic meningomyelitis associated with T-cell lymphoma in a cat.
AB  - A 12-year-old cat was presented for evaluation of progressive tetraparesis.
      Magnetic resonance imaging of the cervical spine demonstrated T2-hyperintensity,
      and contrast enhancement within the C4-C7 spinal cord, with marked meningeal
      contrast enhancement and segmental nerve root thickening. Lumbar cerebrospinal
      fluid contained 407 total nucleated cells/MUL, with 99% eosinophils. The cat
      transiently improved with prednisolone, clindamycin, and ivermectin therapy, but
      subsequently worsened and was euthanized. Necropsy revealed an asymmetric
      infiltration predominantly of the white matter, meninges, and nerve roots of the
      C4-C6 spinal cord segments by an unencapsulated, poorly demarcated neoplasm
      composed of atypical lymphocytes admixed with eosinophils, causing perivascular
      hemorrhage and lytic necrosis. The neoplastic cells were immunoreactive for CD3,
      ultimately confirming T-cell lymphoma.

PMID- 27870074
TI  - From Knowledge to Wisdom: Science and the Good Life.

PMID- 27870073
TI  - From Knowledge to Wisdom: Science and the Good Life.

PMID- 27870075
TI  - Human health in the face of climate change.

PMID- 27870076
TI  - Disaster Mental Health and Positive Psychology: An Afterward to the Special
      Issue.
AB  - The articles in this Special Issue are devoted to integrating the fields of
      disaster mental health and positive psychology. Their focus on resilience
      building, individual and community preparation, meaning making, and posttraumatic
      growth represents an important new development in disaster mental health. The
      overarching goal of this effort is to inform strategies to help both individuals
      including children, adolescent, adult disaster survivors, and relief workers-and
      communities prepare for, respond to, recover from, and possibly even grow
      stronger in the face of adversity. To achieve this goal, this body of literature
      suggests that it is important for disaster mental health workers to partner with
      community leaders, organizations, and the population at large to understand
      community vulnerabilities, take advantage of existing strengths, and respect
      cultural factors implicated in disaster recovery. It further suggests that an
      effective community-based approach to disaster recovery will make psychosocial
      support and skill-building programs available to large numbers of survivors,
      which is critical for responding to future national and international disasters.
      Continued high-quality research that is comprehensive and considers not only
      relevant psychological, social, cultural, and biological factors but also
      interrelations between individuals, organizations and communities is needed to
      advance this relatively new and important direction of the disaster mental health
      field.

PMID- 27870077
TI  - Stem cell bioprinting for applications in regenerative medicine.
AB  - Many regenerative medicine applications seek to harness the biologic power of
      stem cells in architecturally complex scaffolds or microenvironments. Traditional
      tissue engineering methods cannot create such intricate structures, nor can they
      precisely control cellular position or spatial distribution. These limitations
      have spurred advances in the field of bioprinting, aimed to satisfy these
      structural and compositional demands. Bioprinting can be defined as the
      programmed deposition of cells or other biologics, often with accompanying
      biomaterials. In this concise review, we focus on recent advances in stem cell
      bioprinting, including performance, utility, and applications in regenerative
      medicine. More specifically, this review explores the capability of bioprinting
      to direct stem cell fate, engineer tissue(s), and create functional vascular
      networks. Furthermore, the unique challenges and concerns related to bioprinting
      living stem cells, such as viability and maintaining multi- or pluripotency, are
      discussed. The regenerative capacity of stem cells, when combined with the
      structural/compositional control afforded by bioprinting, provides a unique and
      powerful tool to address the complex demands of tissue engineering and
      regenerative medicine applications.

PMID- 27870078
TI  - Cartilage extracellular matrix as a biomaterial for cartilage regeneration.
AB  - The extracellular matrix (ECM) of various tissues possesses the model
      characteristics that biomaterials for tissue engineering strive to mimic;
      however, owing to the intricate hierarchical nature of the ECM, it has yet to be
      fully characterized and synthetically fabricated. Cartilage repair remains a
      challenge because the intrinsic properties that enable its durability and long
      lasting function also impede regeneration. In the last decade, cartilage ECM has
      emerged as a promising biomaterial for regenerating cartilage, partly because of
      its potentially chondroinductive nature. As this research area of cartilage
      matrix-based biomaterials emerged, investigators facing similar challenges
      consequently developed convergent solutions in constructing robust and bioactive
      scaffolds. This review discusses the challenges, emerging trends, and future
      directions of cartilage ECM scaffolds, including a comparison between two
      different forms of cartilage matrix: decellularized cartilage (DCC) and
      devitalized cartilage (DVC). To overcome the low permeability of cartilage
      matrix, physical fragmentation greatly enhances decellularization, although the
      process itself may reduce the chondroinductivity of fabricated scaffolds. The
      less complex processing of a scaffold composed of DVC, which has not been
      decellularized, appears to have translational advantages and potential
      chondroinductive and mechanical advantages over DCC, without detrimental
      immunogenicity, to ultimately enhance cartilage repair in a clinically relevant
      way.

PMID- 27870079
TI  - Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced
      Gastric Cancer.
AB  - STUDY OBJECTIVE: Gastric cancer is the fifth most common malignancy and second
      leading cause of cancer-related mortality. Chemotherapy options for patients who
      fail first-line treatment are limited. Thus the objective of this study was to
      assess the cost-effectiveness of second-line treatment options for patients with
      advanced or metastatic gastric cancer. DESIGN: Cost-effectiveness analysis using
      a Markov model to compare the cost-effectiveness of six possible second-line
      treatment options for patients with advanced gastric cancer who have failed
      previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel
      plus ramucirumab, and palliative care. MEASUREMENTS AND MAIN RESULTS: The model
      was performed from a third-party payer's perspective to compare lifetime costs
      and health benefits associated with studied second-line therapies. Costs included
      only relevant direct medical costs. The model assumed chemotherapy cycle lengths
      of 30 days and a maximum number of 24 cycles. Systematic review of literature was
      performed to identify clinical data sources and utility and cost data. Quality
      adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs)
      were calculated. The primary outcome measure for this analysis was the ICER
      between different therapies, where the incremental cost was divided by the number
      of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold
      that was set at $50,000/QALY gained, and an exploratory analysis using
      $160,000/QALY gained was also used. The model's robustness was tested by using 1
      way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic
      sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was
      associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and
      palliative care were dominated strategies. Paclitaxel and the combination of
      paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of
      $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified
      WTP threshold, our base case analysis demonstrated that irinotecan alone is the
      most cost-effective regimen, and both paclitaxel alone and the combination of
      paclitaxel and ramucirumab were not cost-effective (ICER more than $50,000). Both
      1-way sensitivity analyses and PSA demonstrated the model's robustness. PSA
      illustrated that paclitaxel plus ramucirumab was extremely unlikely to be cost
      effective at a WTP threshold less than $400,000/QALY gained. CONCLUSION:
      Irinotecan alone appears to be the most cost-effective second-line regimen for
      patients with gastric cancer. Paclitaxel may be cost-effective if the WTP
      threshold was set at $160,000/QALY gained.

PMID- 27870080
TI  - Players' Doctors: The Roles Should Be Very Clear.
AB  - Years ago, one of us had the opportunity to talk with a starting guard in the
      National Basketball Association about his health care. The player, then a rookie,
      did not have his own personal doctor. Instead, he received his health care from
      the team doctor. This athlete was very well paid and could have received care
      anywhere he wished in the area. But he came from a very poor neighborhood.
      Growing up, he said, he had no health care other than hearing and eye tests done
      at his school and maybe (he was not sure) vaccinations given by the school nurse.
      The player said he now felt fine and trusted his team to look out for his health
      since they were paying him a lot of money and obviously wanted him on the court.
      While it might seem obvious that conflicts of role could arise for doctors
      working simultaneously for a team and for an athlete-wanting to please coaches,
      owners, and maybe fans while looking out for the athletes on the team-that is not
      how this young player saw things. He trusted his team and those who worked for
      them, and he figured that their interest in keeping him healthy overlapped nicely
      with his interest in staying healthy. As someone who did not get much access to
      health care as a child and had little need for it, he did not have concerns about
      conflicts of interest and second opinions foremost in his mind. But as is clear
      from a recent scandal involving the National Football League and concussion
      research, there are reasons for concern when athletes deal with health care
      workers paid by their teams.

PMID- 27870081
TI  - Preventing Conflicts of Interest of NFL Team Physicians.
AB  - At least since the time of Hippocrates, the physician-patient relationship has
      been the paradigmatic ethical arrangement for the provision of medical care. Yet,
      a physician-patient relationship does not exist in every professional interaction
      involving physicians and individuals they examine or treat. There are several
      "third-party" relationships, mostly arising where the individual is not a patient
      and is merely being examined rather than treated, the individual does not select
      or pay the physician, and the physician's services are provided for the benefit
      of another party. Physicians who treat NFL players have a physician-patient
      relationship, but physicians who merely examine players to determine their health
      status have a third-party relationship. As described by Glenn Cohen et al., the
      problem is that typical NFL team doctors perform both functions, which leads to
      entrenched conflicts of interest. Although there are often disputes about
      treatment, the main point of contention between players and team physicians is
      the evaluation of injuries and the reporting of players' health status to coaches
      and other team personnel. Cohen et al. present several thoughtful recommendations
      that deserve serious consideration. Rather than focusing on their specific
      recommendations, however, I would like to explain the rationale for two essential
      reform principles: the need to sever the responsibilities of treatment and
      evaluation by team physicians and the need to limit the amount of player medical
      information disclosed to teams.

PMID- 27870083
TI  - Being Right Isn't Always Enough: NFL Culture and Team Physicians' Conflict of
      Interest.
AB  - The job of being a sports team physician is difficult, regardless of the level,
      from high school to the National Football League. When a sports league receives
      the intensity of attention leveled at the NFL, though, a difficult occupation
      becomes even more challenging. Even for the NFL players themselves, players' best
      interests regarding health issues are often unclear. Football players are, as a
      lot, highly competitive individuals. They want to win, and they want to help the
      team win. It's a warrior culture, and respect is earned by playing hurt. Should
      the team physician respect a player's autonomy when this means allowing him to
      make choices that might lead to further personal harm, especially if the player's
      choices align with the preference of the coach and management? Or should the
      doctor set limits and balance the player's choices with a paternalistic set of
      constraints, perhaps in opposition to both the player's and the team's desires?
      Simplification of this web of conflicts of interest is the goal of the model
      proposed by Glenn Cohen, Holly Lynch, and Christopher Deubert. In my view, their
      proposal is very clever. As an idea, it meets the expectations its authors set,
      namely, to minimize the problem of conflict of interest in the delivery of health
      care services to NFL football players. The ethics of the proposal align well with
      certain moral goals, like treating the player's interests more fairly and
      treating the player's health as an end instead of as the means to an end. But
      will such a proposal ever make headway in the pressurized environment of the NFL?

PMID- 27870082
TI  - A Proposal to Address NFL Club Doctors' Conflicts of Interest and to Promote
      Player Trust.
AB  - How can we ensure that players in the National Football League receive excellent
      health care they can trust from providers who are as free from conflicts of
      interest as realistically possible? NFL players typically receive care from the
      club's own medical staff. Club doctors are clearly important stakeholders in
      player health. They diagnose and treat players for a variety of ailments,
      physical and mental, while making recommendations to the player concerning those
      ailments. At the same time, club doctors have obligations to the club, namely to
      inform and advise clubs about the health status of players. While players and
      clubs share an interest in player health-both of them want players to be healthy
      so they can play at peak performance-there are several areas where their
      interests can diverge, and the divergence presents legal and ethical challenges.
      The current structure forces club doctors to have obligations to two parties-the
      club and the player-and to make difficult judgments about when one party's
      interests must yield to another's. None of the three parties involved should
      prefer this conflicted approach. We propose to resolve the problem of dual
      loyalty by largely severing the club doctor's ties with the club and refashioning
      that role into one of singular loyalty to the player-patient. The main idea is to
      separate the roles of serving the player and serving the club and replace them
      with two distinct sets of medical professionals: the Players' Medical Staff (with
      exclusive loyalty to the player) and the Club Evaluation Doctor (with exclusive
      loyalty to the club). We begin by explaining the broad ethical principles that
      guide us and that help shape our recommendation. We then provide a description of
      the role of the club doctor in the current system. After explaining the concern
      about the current NFL player health care structure, we provide a recommendation
      for improving this structure. We then discuss how the club medical staff fits
      into the broader microenvironment affecting player health.

PMID- 27870085
TI  - Sponsoring Organizations.

PMID- 27870084
TI  - A Response to Commentaries.
AB  - Our article "NFL Player Health Care: Addressing Club Doctors' Conflicts of
      Interests and Promoting Player Trust" focused on an inherent structural conflict
      that faces club doctors in the National Football League. The conflict stems from
      club doctors' dual role of providing medical care to players and providing
      strategic advice to clubs. We recommended assigning these roles to different
      individuals, with the medical staff members who are responsible for providing
      player care being chosen and subject to review and termination by a committee of
      medical experts selected equally by the NFL and the NFL Players Association.
      Recognizing that the problem of structural conflict of interest is deeply
      entrenched and that our recommendation is a significant departure from the status
      quo, we invited comment from a diverse and highly qualified group of experts.
      There is considerable common ground among the commentators. All but one agreed
      with us that, despite the best intentions of upstanding professionals, there is a
      structural conflict of interest in the club doctors' relationship with players,
      and the commentaries were generally supportive of our recommendation for change.
      There are also meaningful disagreements, however. Some commentators think that
      the proposal is on the right track but does not go far enough to reduce the
      structural conflict of interest, and one commentary wholly disagrees with our
      analysis and recommendations.

PMID- 27870087
TI  - NFL Physicians: Committed to Excellence in Patient-Player Care.
AB  - The National Football League Physicians Society read with disappointment the
      article "A Proposal to Address NFL Club Doctors' Conflicts of Interest and to
      Promote Player Trust." In spite of the authors' suggestions, NFL physicians are
      accomplished medical professionals who abide by the highest ethical standards in
      providing treatment to all of their patients, including those who play in the
      NFL. It defies logic for the authors not to have engaged experienced and active
      NFL physicians from the very start of their effort to explore, challenge, and
      recommend significant alterations to the delivery of health care to NFL players.
      As troubling as this article is from so many perspectives, it does represent an
      opportunity for the NFLPS to set the record straight and call attention to the
      excellent quality of care NFL players receive. In addition, it represents an
      opportunity to expose the extraordinarily weak evidence presented in the article
      and to refute the baseless allegations that challenge the high ethical standards
      of NFL physicians. Contrary to solid scientific research that starts with a
      hypothesis based on theory, in this case, it seems quite apparent that the
      authors started with a predetermined conclusion and set out to justify it. Their
      premise was flawed, and they failed in their execution.

PMID- 27870086
TI  - Health Care for NFL Players: Upholding Physician Standards and Enhancing the
      Doctor-Patient Relationship.
AB  - Beginning my third year with the Kansas City Chiefs and being also a medical
      student at McGill University, I was at first a little reluctant to comment on
      Glenn Cohen et al.'s critique of the National Football League's structure
      involving player health and team doctors, but the opportunity to provide a
      perspective as both a football player and a medical student was too much to
      forgo. Because of my athletic and academic background, I am often asked what I
      think about injuries in professional sports and about the role of sports medicine
      physicians, and Cohen et al.'s article demands a thoughtful reaction. I want to
      suggest that the fundamental principles concerning the medical profession and the
      doctor-patient relationship provide additional arguments for some of the
      solutions that Cohen et al. discuss. The professional self-regulation that the
      proposed medical committee could provide and the reliance on a doctor who was not
      hired by the player's employer-the club-for a second opinion are both good ways
      to minimize conflicts of interest.

PMID- 27870089
TI  - Lessons for the NFL from Workers' Compensation.
AB  - In the article "A Proposal to Address NFL Club Doctors' Conflicts of Interest and
      to Promote Player Trust," Glenn Cohen et al. write, "The [NFL's] current
      structure forces club doctors to have obligations to two parties-the club and the
      player-and to make difficult judgments about when one party's interests must
      yield to another's." I can understand why some might be suspicious about bias in
      the current NFL medical system, in which the club doctors have a professional
      duty to put their player-patients' best interests first yet are employed by
      clubs, which have a primary goal of winning football games. It is my opinion,
      however, that neither the club nor the player needs to be sacrificed. I base this
      opinion partly on my experience as an NFL player in the early 1980s, partly on
      several years as team physician for the Boston Red Sox, and partly on my twenty
      three-years of experience as a physician with the Connecticut Workers'
      Compensation medical system, which supposes that physicians can be fair to both
      workers and employers.

PMID- 27870093
TI  - Erratum.

PMID- 27870090
TI  - The Dual Role of NFL Team Doctors.
AB  - Glenn Cohen, Holly Fernandez Lynch, and Christopher Deubert are right in their
      article "A Proposal to Address NFL Club Doctors' Conflicts of Interest and to
      Promote Player Trust" that the problem with the medical care rendered to National
      Football League players is not that the doctors are bad, but that the system in
      which they provide care is structured badly. We saw some of the problems this
      system causes last season in what happened to Case Kenum, a quarterback for the
      Los Angeles Rams who, despite having a possible concussion from a game injury,
      was allowed to continue to play, with a concussion spotter in the booth and
      coaches, teammates, seven game officials, and two full training staffs present.
      From my experience playing in the league from 1989 to 1999, I do not believe that
      you can eliminate the conflict of interest completely, but I think it can be
      limited to the point that it does not harm the player. As the structure is now,
      with the team paying the club doctor, it is impossible to put the players' health
      and well-being before the team's on-field priorities.

PMID- 27870094
TI  - Patch test nails.

PMID- 27870096
TI  - Allergic contact dermatitis of the face caused by Magnolia officinalis bark
      extract.

PMID- 27870097
TI  - Scutellaria baicalensis extract: a novel botanical allergen in cosmetic products?

PMID- 27870098
TI  - Allergic contact dermatitis caused by argan oil, neem oil, and Mimosa tenuiflora.

PMID- 27870099
TI  - Angioedema-like airborne contact dermatitis caused by Dittrichia viscosa (L.)
      Greuter in a hunter.

PMID- 27870100
TI  - Two cases of eyelid dermatitis caused by cobalt in colour cosmetics.

PMID- 27870101
TI  - Airborne contact dermatitis caused by the sarcotesta of Ginkgo biloba.

PMID- 27870102
TI  - Failure of single-unit restorations on root filled posterior teeth: a systematic
      review.
AB  - This systematic review investigated the failure rate of conventional single-unit
      restorations in root filled posterior permanent teeth. Two reviewers
      independently applied eligibility criteria, extracted data and assessed the
      quality of the evidence of each included study according to the Cochrane
      Collaboration's procedures for randomized control trials (RCTs) and the STROBE
      criteria for observational studies. The MEDLINE (via Ovid), EMBASE (via Ovid),
      Cochrane Oral Health Group Trials Register and CENTRAL (via Cochrane Library)
      databases were searched electronically (January 1993 to week 1, February 2015).
      This was complemented by an additional hand search of selected journals and the
      references of relevant studies. Clinical studies published on root filled single
      unit restorative treatments with a mean follow-up period of at least 3 years were
      selected. The outcome measured was clinical or radiological failure. Overall, the
      four RCTs and the single observational study included were of low and high
      quality, respectively. Therefore, a meta-analysis was not possible. The pooled
      mean failure rates were reported according to the type of treatment and remaining
      coronal tooth structure. The current evidence suggested that the failure rates of
      the treatments may depend on the amount of remaining tooth structure and type of
      treatment. Post-retained crowns were associated with the most favourable outcome
      in teeth with one to two remaining coronal tooth wall(s), whereas post-free
      crowns were superior when greater tooth structure was available. Restorations in
      teeth without ferrules had such a high rate of failure that other treatment
      options should be considered.

PMID- 27870103
TI  - Role of Immunotherapy in Targeting the Bone Marrow Microenvironment in Multiple
      Myeloma: An Evolving Therapeutic Strategy.
AB  - Multiple myeloma (referred to henceforth as myeloma) is a B-cell malignancy
      characterized by unregulated growth of plasma cells in the bone marrow. The
      treatment paradigm for myeloma underwent significant evolution in the last
      decade, with an improved understanding of the pathogenesis of the disease as well
      as the development of therapeutic agents that target not only the tumor cells but
      also their microenvironment. Despite these therapeutic advances, the prognosis of
      patients with relapsed or refractory myeloma remains poor. Accordingly, a need
      exists for new therapeutic avenues that can overcome resistance to current
      therapies and improve survival outcomes. In addition, myeloma is associated with
      progressive immune dysregulation, with defects in T-cell immunity, natural killer
      cell function, and the antigen-presenting capacity of dendritic cells, resulting
      in a tumor microenvironment that promotes disease tolerance and progression.
      Together, the immunosuppressive microenvironment and oncogenic mutations activate
      signaling networks that promote myeloma cell survival. Immunotherapy incorporates
      novel treatment options (e.g., monoclonal antibodies, antibody-drug conjugates,
      chimeric antigen receptor T-cell therapy, immune checkpoint inhibitors,
      bispecific antibodies, and tumor vaccines) either alone or in combination with
      existing lines of therapies (e.g., immunomodulatory agents, proteasome
      inhibitors, and histone deacetylase inhibitors) to enhance the host anti myeloma
      immunity within the bone marrow microenvironment and improve clinical response.
      Following the U.S. Food and Drug Administration approval of daratumumab and
      elotuzumab in 2015, more immunotherapeutic agents are expected to be become
      available as valuable treatment options in the near future. This review provides
      a basic understanding of the role of immunotherapy in modulating the bone marrow
      tumor microenvironment and its role in the treatment of myeloma. Clinical
      efficacy and safety of recently approved therapeutic monoclonal antibodies
      (daratumumab, elotuzumab) are discussed, along with the therapeutic potential of
      emerging immunotherapies (antibody-drug conjugates, chimeric antigen receptor T
      cell therapy, tumor vaccines, and immune checkpoint inhibitors).

PMID- 27870104
TI  - Clinical Experience with Daptomycin in Pediatrics.
AB  - INTRODUCTION: The management of gram-positive infections has been complicated in
      recent years by the emergence of antimicrobial resistance, leaving fewer options
      for therapy. Daptomycin is a lipopeptide antibiotic used for the systemic
      treatment of gram-positive infections. It has a distinct mechanism of action and
      a favorable side effect profile, and it requires once/day dosing. Unfortunately,
      there is a paucity of safety, efficacy, and pharmacokinetic data in neonatal and
      pediatric patients. The objective of this study was to review our experience with
      daptomycin use for the treatment of gram-positive infections in these patient
      populations. METHODS: We conducted a retrospective analysis of electronic medical
      records of hospitalized children who received daptomycin between October 2008 and
      June 2014 for the treatment of proven gram-positive infections. RESULTS: Of the
      146 patients who received at least 3 days of daptomycin therapy, 109 patients had
      a proven gram-positive infection and were included for further analysis. Of the
      109 patients, 71 were males (65%) and the median age was 12 years (range: 2.5 mo
      to 24 yrs). The median duration of therapy was 12 days (range: 3-121 days; mean =
      16 days). Catheter-related bloodstream infections were the most common type of
      infections (n=81 patients) in those receiving daptomycin treatment. One hundred
      seven patients (98%) had documented improvement and resolution at the time of
      hospital discharge. One hundred four patients (95%) had a baseline creatine
      phosphokinase (CPK) level obtained. Of these 104 patients, 48 (46%) had at least
      one follow-up CPK level after the start of therapy. Three patients' charts showed
      laboratory evidence of elevated CPK values. CONCLUSIONS: The majority of patients
      demonstrated clinical improvement after receiving daptomycin as primary therapy
      for proven gram-positive infections. Larger randomized controlled trials focusing
      on safety and efficacy are necessary to assess these outcomes with daptomycin use
      in the pediatric population.

PMID- 27870105
TI  - Evaluating the effects of discriminability on behavioral persistence during and
      following time-based reinforcement.
AB  - With four children with autism we evaluated a refinement to time-based
      reinforcement designed to reduce response persistence when we simultaneously
      introduced time-based reinforcement and extinction. We further evaluated whether
      this refinement mitigated response recurrence when all reinforcer deliveries
      ceased during an extinction-only disruptor phase. The refinement involved
      increasing the saliency of the contingency change from contingent reinforcement
      (during baseline) to time-based reinforcement by delivering different colored
      reinforcers during time-based reinforcement. Behavioral momentum theory predicts
      that increasing the discriminability of the change from variable-interval to
      variable-time reinforcement should lead to faster reductions in responding. We
      present data on four participants, three of whom displayed response patterns
      consistent with the predictions of behavioral momentum theory during time-based
      reinforcement. However, the participants showed more varied patterns of recurrent
      behavior during extinction. We discuss these results within a translational
      research framework focusing on strategies used to mitigate treatment relapse for
      severe destructive behavior, as time-based reinforcement is one of the most
      commonly prescribed interventions for destructive behavior displayed by
      individuals with intellectual and developmental disabilities.

PMID- 27870106
TI  - A two-part mixed effects model for cigarette purchase task data.
AB  - The Cigarette Purchase Task is a behavioral economic assessment tool designed to
      measure the relative reinforcing efficacy of cigarette smoking across different
      prices. An exponential demand equation has become a standard model for analyzing
      purchase task data, but its utility is compromised by its inability to
      accommodate values of zero consumption. We propose a two-part mixed effects model
      that keeps the same exponential demand equation for modeling nonzero consumption
      values, while providing a logistic regression for the binary outcome of zero
      versus nonzero consumption. Therefore, the proposed model can accommodate zero
      consumption values and retain the features of the exponential demand equation at
      the same time. As a byproduct, the logistic regression component of the proposed
      model provides a new demand index, the "derived breakpoint", for the price above
      which a subject is more likely to be abstinent than to be smoking. We apply the
      proposed model to data collected at baseline from college students (N = 1,217)
      enrolled in a randomized clinical trial utilizing financial incentives to
      motivate tobacco cessation. Monte Carlo simulations showed that the proposed
      model provides better fits than an existing model. We note that the proposed
      methodology is applicable to other purchase task data, for example, drugs of
      abuse.

PMID- 27870107
TI  - Stimulus-reinforcer relations established during training determine resistance to
      extinction and relapse via reinstatement.
AB  - The baseline rate of a reinforced target response decreases with the availability
      of response-independent sources of alternative reinforcement; however, resistance
      to disruption and relapse increases. Because many behavioral treatments for
      problem behavior include response-dependent reinforcement of alternative
      behavior, the present study assessed whether response-dependent alternative
      reinforcement also decreases baseline response rates but increases resistance to
      extinction and relapse. We reinforced target responding at equal rates across two
      components of a multiple schedule with pigeons. We compared resistance to
      extinction and relapse via reinstatement of (1) a target response trained
      concurrently with a reinforced alternative response in one component with (2) a
      target response trained either concurrently or in separate components from the
      alternative response across conditions. Target response rates trained alone in
      baseline were higher but resistance to extinction and relapse via reinstatement
      tests were greater after training concurrently with the alternative response. In
      another assessment, training target and alternative responding together, but
      separating them during extinction and reinstatement tests, produced equal
      resistance to extinction and relapse. Together, these findings are consistent
      with behavioral momentum theory-operant response-reinforcer relations determined
      baseline response rates but Pavlovian stimulus-reinforcer relations established
      during training determined resistance to extinction and relapse. These findings
      imply that reinforcing alternative behavior to treat problem behavior could
      initially reduce rates but increase persistence.

PMID- 27870108
TI  - Effects of signaling on temporal control of behavior in response-initiated fixed
      intervals.
AB  - Behavior and events distributed in time can serve as markers that signal delays
      to future events. The majority of timing research has focused on how behavior
      changes as the time to some event, usually food availability, decreases. The
      primary objective of the two experiments presented here was to assess how
      behavior changes as time passes between two time markers when the first time
      marker was manipulated but the second, food delivery, was held constant. Pigeons
      were exposed to fixed-interval, response-initiated fixed-interval, and signaled
      response-initiated fixed-interval 15- and 30-s schedules of reinforcement. In
      Experiment 1, first-response latencies were systematically shorter in the
      signaled response-initiated schedules than response-initiated schedules,
      suggesting that the first response was a more effective time marker when it was
      signaled. In Experiment 2, responding in no-food (i.e. "peak") trials indicated
      that timing accuracy was equivalent in the three schedule types. Compared to
      fixed interval schedules, timing precision was reduced in the signaled response
      initiated schedules and was lowest in response-initiated schedules. Results from
      Experiments 1 and 2 coupled with previous research suggest that the overall
      "informativeness" of a time marker relative to other events and behaviors in the
      environment may determine its efficacy.

PMID- 27870109
TI  - Analyzing large datasets with bootstrap penalization.
AB  - Data with a large p (number of covariates) and/or a large n (sample size) are now
      commonly encountered. For many problems, regularization especially penalization
      is adopted for estimation and variable selection. The straightforward application
      of penalization to large datasets demands a "big computer" with high
      computational power. To improve computational feasibility, we develop bootstrap
      penalization, which dissects a big penalized estimation into a set of small ones,
      which can be executed in a highly parallel manner and each only demands a "small
      computer". The proposed approach takes different strategies for data with
      different characteristics. For data with a large p but a small to moderate n,
      covariates are first clustered into relatively homogeneous blocks. The proposed
      approach consists of two sequential steps. In each step and for each bootstrap
      sample, we select blocks of covariates and run penalization. The results from
      multiple bootstrap samples are pooled to generate the final estimate. For data
      with a large n but a small to moderate p, we bootstrap a small number of
      subjects, apply penalized estimation, and then conduct a weighted average over
      multiple bootstrap samples. For data with a large p and a large n, the natural
      marriage of the previous two methods is applied. Numerical studies, including
      simulations and data analysis, show that the proposed approach has computational
      and numerical advantages over the straightforward application of penalization. An
      R package has been developed to implement the proposed methods.

PMID- 27870110
TI  - The hematology of captive Bobtail lizards (Tiliqua rugosa): blood counts, light
      microscopy, cytochemistry, and ultrastructure.
AB  - INTRODUCTION: Bobtail lizards (Tiliqua rugosa) are native to Australia. The only
      previous study on the hematology of this species documented just 6 animals.
      OBJECTIVES: The aims of this study were to characterize the light microscopy,
      ultrastructure and cytochemistry of blood cells, and evaluate CBCs of captive
      Bobtail lizards. METHODS: Over 2 consecutive summers, heparinized venous blood
      was collected from the ventral coccygeal vein of 46 clinically healthy, captive
      indoor- or outdoor-housed adult Bobtails. Complete blood cell counts and smear
      evaluations were performed, and cytochemical stains and transmission electron
      microscopy were used to further characterize blood cells. RESULTS: The
      eosinophils of this species were uniformly vacuolated: a unique feature not
      previously reported in reptiles. Heterophils were the predominant leukocyte, with
      fewer lymphocytes, azurophilic and nonazurophilic monocytes, occasional
      eosinophils, and basophils. Thrombocytes were frequently clumped. Slight
      polychromasia (0-15% of erythrocytes) was typically present. Hemogregarine
      parasites were seen on some smears. The range of CBC results was often wide. The
      PCV ranged from 11% to 38%. Total plasma proteins by refractometry were between
      3.5 and 7.8 g/dL. Hemoglobin ranged between 2.6 and 12.6 g/dL by the modified
      hemoglobin-hydroxylamine method. Manual RBC count was 0.35-1.27 * 106 /MUL, and
      WBC count was 2.86-22.66 * 103 /MUL. Bobtail lizards housed outdoors had lower
      PCVs than indoor-housed animals. Bobtails with hemogregarine infections had lower
      PCVs than noninfected lizards. CONCLUSIONS: Ranges for CBC data were often very
      wide, influenced by preanalytic and analytic factors. Hemogregarine infection is
      associated with a decreased PCV, suggesting that some hemogregarine species are
      pathogenic in this population.

PMID- 27870112
TI  - Erratum.

PMID- 27870114
TI  - The Molecular Genetics of Autosomal Recessive Nonsyndromic Intellectual
      Disability: a Mutational Continuum and Future Recommendations.
AB  - Intellectual disability (ID) is a clinical manifestation of the central nervous
      system without any major dysmorphologies of the brain. Biologically it affects
      learning capabilities, memory, and cognitive functioning. The basic defining
      features of ID are characterized by IQ<70, age of onset before 18 years, and
      impairment of at least two of the adaptive skills. Clinically it is classified in
      a syndromic (with additional abnormalities) and a nonsyndromic form (with only
      cognitive impairment). The study of nonsyndromic intellectual disability (NSID)
      can best explain the pathophysiology of cognition, intelligence and memory.
      Genetic analysis in autosomal recessive nonsyndrmic ID (ARNSID) has mapped 51
      disease loci, 34 of which have revealed their defective genes. These genes play
      diverse physiological roles in various molecular processes, including
      methylation, proteolysis, glycosylation, signal transduction, transcription
      regulation, lipid metabolism, ion homeostasis, tRNA modification, ubiquitination
      and neuromorphogenesis. High-density SNP array and whole exome sequencing has
      increased the pace of gene discoveries and many new mutations are being published
      every month. The lack of uniform criteria has assigned multiple identifiers (or
      accession numbers) to the same MRT locus (e.g. MRT7 and MRT22). Here in this
      review we describe the molecular genetics of ARNSID, prioritize the candidate
      genes in uncharacterized loci, and propose a new nomenclature to reorganize the
      mutation data that will avoid the confusion of assigning duplicate accession
      numbers to the same ID locus and to make the data manageable in the future as
      well.

PMID- 27870113
TI  - Targeted Resequencing of Deafness Genes Reveals a Founder MYO15A Variant in
      Northeastern Brazil.
AB  - Identifying the genetic etiology in a person with hearing loss (HL) is
      challenging due to the extreme genetic heterogeneity in HL and the population
      specific variability. In this study, after excluding GJB2 variants, targeted
      resequencing of 180 deafness-related genes revealed the causative variants in 11
      of 19 (58%) Brazilian probands with autosomal recessive HL. Identified pathogenic
      variants were in MYO15A (10 families) and CLDN14 (one family). Remarkably, the
      MYO15A p.(Val1400Met) variant was identified in eight families from the city of
      Monte Santo in the northeast region of Brazil. Haplotype analysis of this variant
      was consistent with a single founder. No other cases with this variant were
      detected among 105 simplex cases from other cities of northeastern Brazil,
      suggesting that this variant is confined to a geographical region. This study
      suggests that it is feasible to develop population-specific screening for
      deafness variants once causative variants are identified in different
      geographical groups.

PMID- 27870115
TI  - MICA Gene Deletion in 3411 DNA Samples from Five Distinct Populations in Mainland
      China and Lack of Association with Nasopharyngeal Carcinoma (NPC) in a Southern
      Chinese Han population.
AB  - Deletion of major histocompatibility complex class I chain-related genes A
      (MICA*Del) was investigated in 3,411 DNA samples from two southern Chinese Han
      populations (Hunan Han, HNH; Guangdong Han, GDH), two northern Chinese
      populations (Inner Mongolia Han, IMH; Inner Mongolia Mongol, IMM) and one
      southeastern Chinese Han population (Fujian Han, FJH) using an in-house
      polymerase chain reaction-sequence specific priming (PCR-SSP) assay, which
      enables direct discrimination between heterozygote and homozygote for MICA*Del.
      MICA*Del showed a frequency ranging from 0.8% in FJH to 5.7% in IMM (Pcorrected <
      0.05), indicating northward increase in frequency of MICA*Del in Chinese
      populations. In contrast to the association reported recently in a Taiwan Chinese
      population and a Malaysian Chinese cohort, MICA*Del distribution did not differ
      between 1,120 patients with nasopharyngeal carcinoma (NPC) and 1,483 normal
      controls in the HNH population (1.03% in NPC cases vs 1.18% in the controls, OR
      (95% CI) = 0.87 (0.51-1.47), p = 0.69). Further gender-stratified analysis also
      failed to disclose any male-specific association reported in a Taiwan Chinese
      population. Multi-locus typing of the 94 samples carrying MICA*Del revealed two
      new haplotypes, HLA-A*11:01-B*13:01-MICA*Del-MICB*009N-DRB1*04:06 and HLA-B*35:01
      MICA*Del-MICB*009N-DRB1*15:01, in addition to HLA-B*48-MICA*Del. Unexpectedly,
      two samples with MICA*Del in the HNH population were each consistently found to
      have two distinct MICA alleles, indicating the existence of two MICA gene copies
      on certain HLA haplotypes. Based on the results from a sizeable case-control
      study, our data suggest that there is no association between MICA*Del and NPC in
      the southern Chinese Han population.

PMID- 27870117
TI  - Embracing Change.

PMID- 27870116
TI  - Therapy processes, progress, and outcomes for 2 therapies for gynecological
      cancer patients.
AB  - OBJECTIVE: Although a number of effective psychotherapies have been identified
      for cancer patients, little is known about therapy processes, as they unfold the
      course of treatment and the role of therapy processes in treatment outcome. We
      used growth curve modeling to evaluate the associations between therapy processes
      and outcomes among gynecological cancer patients participating in 2 types of
      therapy. METHODS: Two hundred twenty five women newly diagnosed with
      gynecological cancer were randomly assigned to receive 8 sessions of a coping and
      communication intervention or a client-centered supportive therapy. Participants
      completed measures of preintervention and postintervention depression, working
      alliance after Session 2, and postsession progress and depressive symptoms after
      each session. Therapists completed measures of perceived patient progress.
      RESULTS: Both patients and therapists reported a steady increase in session
      progress and patients reported a steady decrease in depressive symptoms over the
      course of both the coping and communication intervention and client-centered
      supportive sessions. Perceived progress in one session predicted progress in the
      subsequent session. Early working alliance predicted improved session progress
      and reductions in postsession depressive symptoms over sessions. Working alliance
      did not predict prepost treatment changes in depression. Patient-rated session
      progress predicted greater reductions in pretreatment to posttreatment
      depression, but therapist-rated progress did not. CONCLUSIONS: For 2 types of
      treatment delivered to women diagnosed with gynecological cancer, patient-rated
      session progress and depressive symptoms rated over therapy sessions may serve as
      a yardstick that can be useful to therapists to gauge patient's response to
      treatment.

PMID- 27870118
TI  - Re: Terracini et al. Comments on the causation of malignant mesothelioma:
      Rebutting the false concept that recent exposures to asbestos do not contribute
      to causation of mesothelioma. Am J Ind Med 2016;59:506-507.

PMID- 27870119
TI  - Does resistance exercise exert a role in hippocampal neurogenesis?

PMID- 27870121
TI  - Sensory processing during absence seizures.

PMID- 27870120
TI  - Continuous attractor network models of grid cell firing based on excitatory
      inhibitory interactions.
AB  - Neurons in the medial entorhinal cortex encode location through spatial firing
      fields that have a grid-like organisation. The challenge of identifying
      mechanisms for grid firing has been addressed through experimental and
      theoretical investigations of medial entorhinal circuits. Here, we discuss
      evidence for continuous attractor network models that account for grid firing by
      synaptic interactions between excitatory and inhibitory cells. These models
      assume that grid-like firing patterns are the result of computation of location
      from velocity inputs, with additional spatial input required to oppose drift in
      the attractor state. We focus on properties of continuous attractor networks that
      are revealed by explicitly considering excitatory and inhibitory neurons, their
      connectivity and their membrane potential dynamics. Models at this level of
      detail can account for theta-nested gamma oscillations as well as grid firing,
      predict spatial firing of interneurons as well as excitatory cells, show how
      gamma oscillations can be modulated independently from spatial computations,
      reveal critical roles for neuronal noise, and demonstrate that only a subset of
      excitatory cells in a network need have grid-like firing fields. Evaluating
      experimental data against predictions from detailed network models will be
      important for establishing the mechanisms mediating grid firing.

PMID- 27870122
TI  - Neural mechanisms for spatial computation.

PMID- 27870123
TI  - Neurogenic hyperalgesia: illuminating its mechanisms with an infrared laser.

PMID- 27870124
TI  - Are stem cell-derived neural cells physiologically credible?

PMID- 27870125
TI  - Corrigendum: Ion strength limit of computed excess functions based on the
      linearized poisson-boltzmann equation.

PMID- 27870126
TI  - Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of
      Recent Efforts.
AB  - Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused
      by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the
      coding region of specific genes. This leads to the production of pathogenic
      proteins containing critically expanded tracts of glutamines. Although polyQ
      diseases are individually rare, the fact that these nine diseases are
      irreversibly progressive over 10 to 30 years, severely impairing and ultimately
      fatal, usually implicating the full-time patient support by a caregiver for long
      time periods, makes their economic and social impact quite significant. This has
      led several researchers worldwide to investigate the pathogenic mechanism(s) and
      therapeutic strategies for polyQ diseases. Although research in the field has
      grown notably in the last decades, we are still far from having an effective
      treatment to offer patients, and the decision of which compounds should be
      translated to the clinics may be very challenging. In this review, we provide a
      comprehensive and critical overview of the most recent drug discovery efforts in
      the field of polyQ diseases, including the most relevant findings emerging from
      two different types of approaches-hypothesis-based candidate molecule testing and
      hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the
      preclinical studies as well as all the clinical trials performed to date, aiming
      to provide a useful framework for increasingly successful future drug discovery
      and development efforts.

PMID- 27870127
TI  - Study Explores Cost Benefits of Optimising Pregnancy Outcome.

PMID- 27870128
TI  - Validity and power considerations on hypothesis testing under minimization.

PMID- 27870129
TI  - Comments on 'Validity and power considerations on hypothesis testing under
      minimization': by Z. Xu, M. Proschan, and S. Lee, Statistics in Medicine 2016.

PMID- 27870130
TI  - Estimating hazard ratios in cohort data with missing disease information due to
      death.
AB  - In clinical and epidemiological studies information on the primary outcome of
      interest, that is, the disease status, is usually collected at a limited number
      of follow-up visits. The disease status can often only be retrieved
      retrospectively in individuals who are alive at follow-up, but will be missing
      for those who died before. Right-censoring the death cases at the last visit (ad
      hoc analysis) yields biased hazard ratio estimates of a potential risk factor,
      and the bias can be substantial and occur in either direction. In this work, we
      investigate three different approaches that use the same likelihood contributions
      derived from an illness-death multistate model in order to more adequately
      estimate the hazard ratio by including the death cases into the analysis: a
      parametric approach, a penalized likelihood approach, and an imputation-based
      approach. We investigate to which extent these approaches allow for an unbiased
      regression analysis by evaluating their performance in simulation studies and on
      a real data example. In doing so, we use the full cohort with complete illness
      death data as reference and artificially induce missing information due to death
      by setting discrete follow-up visits. Compared to an ad-hoc analysis, all
      considered approaches provide less biased or even unbiased results, depending on
      the situation studied. In the real data example, the parametric approach is seen
      to be too restrictive, whereas the imputation-based approach could almost
      reconstruct the original event history information.

PMID- 27870132
TI  - Retraction: "Oral Polypodium leucomotos increases the anti-inflammatory and
      melanogenic responses of the skin to different modalities of sun exposures: a
      pilot study" by Calzavara-Pinton PG, Rossi MT, Zanca A, Arisi M, Gonzalez S, and
      Venturini M.
AB  - The above article, published online on November 6, 2015 in Wiley Online Library
      (wileyonlinelibrary.com), has been retracted by agreement between the authors,
      the journal Editor in Chief, Thomas M. Ruenger, MD PhD and John Wiley & Sons Ltd.
      The retraction has been agreed as the clinical trial reported in this manuscript
      was not approved by the local Ethics Committee. Reference Calzavara-Pinton PG,
      Rossi MT, Zanca A, Arisi M, Gonzalez S, Venturini M. Oral Polypodium leucomotos
      increases the anti-inflammatory and melanogenic responses of the skin to
      different modalities of sun exposures: a pilot study. Photodermatol Photoimmunol
      Photomed 2016; 32: 22-27. doi: 10.1111/phpp.12209.

PMID- 27870135
TI  - Independent assessment of matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI-MS) sample preparation quality: Effect of sample preparation
      on MALDI-MS of synthetic polymers.
AB  - RATIONALE: Matrix-assisted laser desorption/ionization mass spectrometry (MALDI
      MS) provides detailed and in-depth information about the molecular
      characteristics of synthetic polymers. To obtain the most accurate results the
      sample preparation parameters should be chosen to suit the sample and the aim of
      the experiment. Because the underlying principles of MALDI are still not fully
      known, a priori determination of optimal sample preparation protocols is often
      not possible. METHODS: Employing an automated sample preparation quality
      assessment method recently presented by us we quantified the sample preparation
      quality obtained using various sample preparation protocols. Six conventional
      matrices with and without added potassium as a cationization agent and six ionic
      liquid matrices (ILMs) were assessed using poly(ethylene glycol) (PEG),
      polytetrahydrofuran (PTHF) and poly(methyl methacrylate) (PMMA) as samples. All
      sample preparation protocols were scored and ranked based on predefined quality
      parameters and spot-to-spot repeatability. RESULTS: Clearly distinctive
      preferences were observed in matrix identity and cationization agent for PEG,
      PTHF and PMMA, as the addition of an excess of potassium cationization agent
      results in an increased score for PMMA and a contrasting matrix-dependent effect
      for PTHF and PEG. The addition of excess cationization agent to sample mixtures
      dissipates any overrepresentation of high molecular weight polymer species. Our
      results show reduced ionization efficiency and similar sample deposit homogeneity
      for all tested ILMs, compared with well-performing conventional MALDI matrices.
      CONCLUSIONS: The results published here represent a start in the unsupervised
      quantification of sample preparation quality for MALDI samples. This method can
      select the best sample preparation parameters for any synthetic polymer sample
      and the results can be used to formulate hypotheses on MALDI principles.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27870139
TI  - Corrigendum.

PMID- 27870138
TI  - Promise of Combining Antifungal Agents in Denture Adhesives to Fight Candida
      Species Infections.
AB  - PURPOSE: Several complications may arise in patients wearing complete prosthetic
      appliances, including denture-associated infections and mucosal stomatitis due to
      Candida species. This study evaluated the activity of anti-Candida agents in
      denture adhesive and the cytotoxicities of these preparations for primary human
      gingival epithelial (GE) keratinocytes. MATERIALS AND METHODS: The anti-Candida
      activities of antimicrobial peptides, antimicrobial lipids, and antifungal agents
      against C. albicans ATCC 64124 or HMV4C were assessed in microdilution assays
      containing water or 1% denture adhesive. The minimal inhibitory concentrations
      (MIC) and the minimal bactericidal concentrations (MBC) were determined. The
      cytotoxicities of denture adhesive compounded with these agents were assessed in
      1.0 * 105 primary GE keratinocytes in LGM-3 media with resazurin. RESULTS:
      Lactoferricin B, SMAP28, sphingosine, dihydrosphingosine, and phytosphingosine in
      1% denture adhesive lost antimicrobial activity for C. albicans (p < 0.05).
      Amphotericin B, chlorhexidine dihydrochloride, chlorhexidine gluconate,
      fluconazole, and nystatin in 1% denture adhesive or compounded directly into
      denture adhesive and then diluted to 1% adhesive, did not lose antimicrobial
      activity. Compounded formulations were not cytotoxic (LD50 > 100.0 MUg/ml)
      against primary human GE keratinocytes. CONCLUSIONS: Antimicrobial peptides and
      antimicrobial lipids had diminished activities in 1% adhesive, suggesting that
      components in adhesives may inactivate local innate immune factors in the oral
      cavity, possibly predisposing denture wearers to Candida species infections. More
      importantly, antifungal agents retained their anti-C. albicans activities in
      denture adhesive, strongly suggesting that antifungal agents could be candidates
      for inclusion in adhesive formulations and used as prescribed topical treatments
      for individuals with denture stomatitis.

PMID- 27870140
TI  - Life Finds a Way: Novel Algae in Reactor Cooling Ponds.

PMID- 27870142
TI  - Editorial for 31,4.

PMID- 27870141
TI  - Periodontal tissue engineering by nano beta-tricalcium phosphate scaffold and
      fibroblast growth factor-2 in one-wall infrabony defects of dogs.
AB  - BACKGROUND AND OBJECTIVE: Nanoparticle bioceramics are being investigated for
      biomedical applications. We fabricated a regenerative scaffold comprising type I
      collagen and beta-tricalcium phosphate (beta-TCP) nanoparticles. Fibroblast
      growth factor-2 (FGF-2) is a bioeffective signaling molecule that stimulates cell
      proliferation and wound healing. This study examined the effects, on bioactivity,
      of a nano-beta-TCP/collagen scaffold loaded with FGF-2, particularly on
      periodontal tissue wound healing. MATERIAL AND METHODS: Beta-tricalcium phosphate
      was pulverized into nanosize particles (84 nm) and was then dispersed. A nano
      beta-TCP scaffold was prepared by coating the surface of a collagen scaffold with
      a nanosize beta-TCP dispersion. Scaffolds were characterized using scanning
      electron microscopy, compressive testing, cell seeding and rat subcutaneous
      implant testing. Then, nano-beta-TCP scaffold, nano-beta-TCP scaffold loaded with
      FGF-2 and noncoated collagen scaffold were implanted into a dog one-wall
      infrabony defect model. Histological observations were made at 10 d and 4 wk
      postsurgery. RESULTS: Scanning electron microscopy images show that TCP
      nanoparticles were attached to collagen fibers. The nano-beta-TCP scaffold showed
      higher compressive strength and cytocompatibility compared with the noncoated
      collagen scaffold. Rat subcutaneous implant tests showed that the DNA contents of
      infiltrating cells in the nano-beta-TCP scaffold and the FGF-2-loaded scaffold
      were approximately 2.8-fold and 3.7-fold greater, respectively, than in the
      collagen scaffold. Histological samples from the periodontal defect model showed
      about five-fold greater periodontal tissue repair following implantation of the
      nano-beta-TCP scaffold loaded with FGF-2 compared with the collagen scaffold.
      CONCLUSION: The beta-TCP nanoparticle coating strongly improved the collagen
      scaffold bioactivity. Nano-beta-TCP scaffolds containing FGF-2 are anticipated
      for use in periodontal tissue engineering.

PMID- 27870143
TI  - List of Contributor for HPM 31:4.

PMID- 27870146
TI  - Special issue: Environmental interactions.

PMID- 27870144
TI  - Identifying Research Priorities in Midwifery, a Multinational Delphi Survey.

PMID- 27870148
TI  - Achievement indicators for researchers who publish in Indoor Air.

PMID- 27870147
TI  - Management strategies in Lynch syndrome and familial adenomatous polyposis: a
      national healthcare survey in Japan.
AB  - Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of
      hereditary colorectal cancer (CRC) and are associated with other malignancies.
      There is some heterogeneity in management strategies in Japan. We undertook a
      survey of management of hereditary CRC in hospitals that are members of the Japan
      Society of Colorectal Cancer Research. One hundred and ninety departments
      responded, of which 127 were from designated cancer care hospitals (DCCHs)
      according to the Japanese government. There were 25 488 operations for CRC in
      these departments in 2015. The DCCHs performed better with regard to usage of
      Japan Society of Colorectal Cancer Research guidelines, referring new CRC
      patients for LS screening, and having in-house genetic counselors and knowledge
      of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing
      follow-up in 2011-2015, which is fewer than the number expected from CRC
      operations in 2015. These numbers were not affected by whether the institution
      was a DCCH. Universal screening for LS was carried out in 8% of the departments.
      In contrast, 541 patients were diagnosed with FAP and 273 received preventive
      proctocolectomy/colectomy in 2011-2015. The DCCH departments undertook more
      surgery than non-DCCH departments, although most of the management, including
      surgical procedures and use of non-steroidal anti-inflammatory drugs, was
      similar. Management of desmoid tumor in the abdominal cavity differed according
      to the number of patients treated. In conclusion, there was heterogeneity in
      management of LS but not FAP. Most patients with LS may be overlooked and
      universal screening for LS is not common in Japan.

PMID- 27870149
TI  - Development of sociality and emergence of independence in a killer whale (Orcinus
      orca) calf from birth to 36 months.
AB  - Dolphin calves spend most of their time swimming with their mother immediately
      after birth. As they mature, the calves become increasingly independent, and
      begin to interact more often with other calves, juveniles, and sub-adults. For
      bottlenose dolphin calves, sociality is related to maternal behaviors.
      Unfortunately, much less is known about the development of sociality and
      emergence of independence for killer whale calves. The purpose of this study was
      to examine the developmental changes in social behaviors and solitary activities
      of a killer whale calf across a 36-month period. Focal follow video recordings of
      a mother-calf pair housed at SeaWorld San Antonio were collected 2-6 times a day
      for 5-15 min at 6-month intervals. Using a sample of randomly selected video
      recordings at each month, developmental changes in swims and social interactions
      with her mother, swims and social interactions with non-maternal partners, and
      solitary activities (e.g., solitary swims, solitary play) were observed across
      the months. The calf spent most of her time swimming with the mother across the
      36-month period. The time the calf socialized with her mother was greater than
      the time she socialized with others at each month. Besides her mother, the calf
      socialized more often with the other adult female compared to adult males. As the
      calf matured, the increase in the time she spent socializing with adult killer
      whales other than the mother corresponded with an increase in the rate and time
      spent in solitary play. The developmental trends of sociality and emerging
      independence replicate research conducted with calves of other dolphin species.
      Zoo Biol. 36:11-20, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870150
TI  - Corrigendum.

PMID- 27870151
TI  - Ph-like acute lymphoblastic leukemia with a novel PAX5-KIDINS220 fusion
      transcript.
AB  - Although "paired box 5" (PAX5)-related fusion genes are well documented in
      childhood B-cell precursor acute lymphoblastic leukemia (ALL), these types of
      fusion with the exception of PAX5-JAK2 are rarely seen in patients with gene
      expression profiles similar to those of BCR-ABL1 (Philadelphia)-positive ALL (Ph
      like ALL). We report a novel fusion of the genes PAX5 and "kinase D-interacting
      substrate of 220 kDa" (KIDINS220, also known as ARMS) in a Ph-like ALL. As PAX5
      is a master regulator of B-lymphocyte differentiation, PAX5 rearrangements induce
      a differentiation block in B lymphocytes. KIDINS220 is a mediator of multiple
      receptor signaling pathways, interacts with both T- and B-cell receptors, and is
      necessary for sustained extracellular signal-regulated kinase (ERK) signaling.
      Although functional studies are needed, the PAX5-KIDINS220 fusion protein might
      not only inhibit wild-type PAX5 function, but also promote sustained activation
      of the ERK signaling pathway through upregulation of KIDINS220. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870152
TI  - Practical aspects of gene regulatory inference via conditional inference forests
      from expression data.
AB  - Gene regulatory network (GRN) inference is an active area of research that
      facilitates understanding the complex interplays between biological molecules. We
      propose a novel framework to create such GRNs, based on Conditional Inference
      Forests (CIFs) as proposed by Strobl et al. Our framework consists of using
      ensembles of Conditional Inference Trees (CITs) and selecting an appropriate
      aggregation scheme for variant selection prior to network construction. We show
      on synthetic microarray data that taking the original implementation of CIFs with
      conditional permutation scheme (CIFcond ) may lead to improved performance
      compared to Breiman's implementation of Random Forests (RF). Among all newly
      introduced CIF-based methods and five network scenarios obtained from the DREAM4
      challenge, CIFcond performed best. Networks derived from well-tuned CIFs,
      obtained by simply averaging P-values over tree ensembles (CIFmean ) are
      particularly attractive, because they combine adequate performance with
      computational efficiency. Moreover, thresholds for variable selection are based
      on significance levels for P-values and, hence, do not need to be tuned. From a
      practical point of view, our extensive simulations show the potential advantages
      of CIFmean -based methods. Although more work is needed to improve on speed,
      especially when fully exploiting the advantages of CITs in the context of
      heterogeneous and correlated data, we have shown that CIF methodology can be
      flexibly inserted in a framework to infer biological interactions. Notably, we
      confirmed biologically relevant interaction between IL2RA and FOXP1, linked to
      the IL-2 signaling pathway and to type 1 diabetes.

PMID- 27870154
TI  - Lipidomics analysis of long-chain fatty acyl-coenzyme As in liver, brain, muscle
      and adipose tissue by liquid chromatography/tandem mass spectrometry.
AB  - RATIONALE: Long-chain fatty acyl-coenzyme As (FA-CoAs) are important bioactive
      molecules, playing key roles in biosynthesis of fatty acids, membrane trafficking
      and signal transduction. Development of sensitive analytical methods for
      profiling theses lipid species in various tissues is critical to understand their
      biological activity. A high-pressure liquid chromatography/tandem mass
      spectrometry method has been developed for the quantitative analysis and
      screening of long-chain FACoAs in liver, brain, muscle and adipose tissue.
      METHODS: The sample preparation method consists of tissue homogenization,
      extraction with organic solvent and reconstitution in an ammonium hydroxide
      buffer. Extracts are separated by liquid chromatography (LC) on a reversed-phase
      column and detected by electrospray ionization tandem mass spectrometry (ESI
      MS/MS) in positive mode. An additional neutral loss scan allows for untargeted FA
      CoAs screening. RESULTS: Extraction was optimized for low sample load (10 mg) of
      four tissue types (liver, brain, muscle and adipose tissue) with recoveries
      between 60-140% depending on the analyte and tissue type. Targeted quantification
      was validated for ten FA-CoAs in the range 0.1-500 ng/mL with accuracies between
      85-120%. CONCLUSIONS: We have developed and validated a LC/MS/MS method for the
      quantifications and screening of long-chain FA-CoAs in four different types of
      mammalian tissue. The extraction method is straightforward and long-chain FA-CoA
      species can be quantified using only minimum amount of tissue. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27870156
TI  - Combinations and loads of bacteria affect the cytokine production by fetal
      membranes: An in vitro study.
AB  - PROBLEM: The polybacterial invasion and inflammation of the amniotic cavity is a
      common scenario in PTB, and then, we analyzed the cytokine production by human
      fetal membranes to better understand the host response to polybacterial
      infections. METHOD OF STUDY: Fetal membranes were treated by heat-inactivated
      genital mycoplasmas and Gardnerella vaginalis at 103 or 106 colony/color-forming
      units/mL alone or in combination. Cytokines/receptors were measured in the medium
      by immunoassays. RESULTS: Stimulation of genital mycoplasmas did not increase the
      proinflammatory cytokines, except Ureaplasma urealyticum that increased IL-8
      levels. However, U. urealyticum and Mycoplasma hominis significantly increased IL
      10 and IL-13 levels. G. vaginalis alone or in combination with genital
      mycoplasmas showed an increased proinflammatory and anti-inflammatory cytokines.
      CONCLUSIONS: G. vaginalis sustain a proinflammatory response in the fetal
      membranes in vitro, while genital mycoplasmas induce a strong control of the
      inflammatory response. The ability of genital mycoplasmas to control the
      proinflammatory response may favor their survival in the upper genital tract.

PMID- 27870158
TI  - Erratum.

PMID- 27870157
TI  - Subacute Radiation Dermatitis after Fluoroscopy.

PMID- 27870155
TI  - Timing of Maternal Exposure and Foetal Sex Determine the Effects of Low-level
      Chemical Mixture Exposure on the Foetal Neuroendocrine System in Sheep.
AB  - We have shown that continuous maternal exposure to the complex mixture of
      environmental chemicals (ECs) found in human biosolids (sewage sludge), disrupts
      mRNA expression of genes crucial for development and long-term regulation of
      hypothalamic-pituitary gonadal (HPG) function in sheep. The present study
      investigated whether exposure to ECs only during preconceptional period or only
      during pregnancy perturbed key regulatory genes within the hypothalamus and
      pituitary gland and whether these effects were different from chronic (life-long)
      exposure to biosolid ECs. The findings demonstrate that the timing and duration
      of maternal EC exposure influences the subsequent effects on the foetal
      neuroendocrine system in a sex-specific manner. Maternal exposure prior to
      conception, or during pregnancy only, altered the expression of key foetal
      neuroendocrine regulatory systems such as gonadotrophin-releasing hormone and
      kisspeptin to a greater extent than when maternal exposure was 'life-long'.
      Furthermore, hypothalamic gene expression was affected to a greater extent in
      males than in females and, following EC exposure, male foetuses expressed more
      'female-like' mRNA levels for some key neuroendocrine genes. This is the first
      study to show that 'real-life' maternal exposure to low levels of a complex
      cocktail of chemicals prior to conception can subsequently affect the developing
      foetal neuroendocrine system. These findings demonstrate that the developing
      neuroendocrine system is sensitive to EC mixtures in a sex-dimorphic manner
      likely to predispose to reproductive dysfunction in later life.

PMID- 27870160
TI  - Erratum.

PMID- 27870159
TI  - BRAF V600E is not a consistent feature of myopericytoma.

PMID- 27870163
TI  - Public Health Nurses in Cancer Care: Broadening the Intersection.

PMID- 27870162
TI  - Galectin-3 contributes to vascular fibrosis in monocrotaline-induced pulmonary
      arterial hypertension rat model.
AB  - Galectin-3 (Gal-3) plays a critical role in vascular inflammation and fibrosis.
      The role of TGF-beta1 in mediating pulmonary vascular fibrosis is well
      documented; thus, we suspected that Gal-3 could be an important factor in TGF
      beta1-induced fibrosis in pulmonary adventitial fibroblasts (PAFs). We treated
      rats with monocrotaline (MCT) and cultured PAFs with TGF-beta1 to stimulate
      fibrosis. We found that MCT injection induced vessel thickening and extracellular
      matrix deposition in vivo. TGF-beta1 stimulated the production of collagen and
      fibronectin (Fn) protein in vitro. TGF-beta1 promoted the expression of Gal-3 and
      its translocation, while silencing Gal-3 reduced Col-1a deposition. Blockage of
      STAT3 decreased the expression of Gal-3 induced by TGF-beta1. Gal-3 increased Col
      1a accumulation and downregulated matrix metallopeptidase 9 (MMP-9) expression in
      PAFs, but it did not affect Fn expression. These findings demonstrate that Gal-3
      is required for TGF-beta1-stimulated vascular fibrosis via a STAT3 signaling
      cascade and that MMP-9 is also involved in TGF-beta1/Gal-3-induced vascular
      fibrosis.

PMID- 27870166
TI  - The frontier spirit and reproducible research in animal breeding.

PMID- 27870167
TI  - Design of Complete Dentures by Adopting CAD Developed for Fixed Prostheses.
AB  - The demand for complete dentures is expected to increase worldwide, but complete
      dentures are mainly designed and fabricated manually involving a broad series of
      clinical and laboratory procedures. Therefore, the quality of complete dentures
      largely depends on the skills of the dentist and technician, leading to
      difficulty in quality control. Computer-aided design and manufacturing (CAD/CAM)
      has been used to design and fabricate various dental restorations including
      dental inlays, veneers, crowns, partial crowns, and fixed partial dentures
      (FPDs). It has been envisioned that the application of CAD/CAM technology could
      reduce intensive clinical/laboratory work for the fabrication of complete
      dentures; however, CAD/CAM is seldom used to fabricate complete dentures due to
      the lack of suitable CAD software to design virtual complete dentures although
      the CAM techniques are in a much advanced stage. Here we report the successful
      design of virtual complete dentures using CAD software of 3Shape Dental System
      2012, which was developed for designing fixed prostheses instead of complete
      dentures. Our results demonstrated that complete dentures could be successfully
      designed by the combination of two modeling processes, single coping and full
      anatomical FPD, available in the 3Shape Dental System 2012.

PMID- 27870170
TI  - Abandoning cricoid pressure.

PMID- 27870169
TI  - Comparison of dynamic magnetic resonance defaecography with rectal contrast and
      conventional defaecography for posterior pelvic floor compartment prolapse.
AB  - AIM: This study compared the diagnostic capabilities of dynamic magnetic
      resonance defaecography (D-MRI) with conventional defaecography (CD, reference
      standard) in patients with symptoms of prolapse of the posterior compartment of
      the pelvic floor. METHOD: Forty-five consecutive patients underwent CD and D-MRI.
      Outcome measures were the presence or absence of rectocele, enterocele,
      intussusception, rectal prolapse and the descent of the anorectal junction on
      straining, measured in millimetres. Cohen's Kappa, sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV) and the positive
      and negative likelihood ratio of D-MRI were compared with CD. Cohen's Kappa and
      Pearson's correlation coefficient were calculated and regression analysis was
      performed to determine inter-observer agreement. RESULTS: Forty-one patients were
      available for analysis. D-MRI underreported rectocele formation with a difference
      in prevalence (CD 77.8% vs D-MRI 55.6%), mean protrusion (26.4 vs 22.7 mm, P =
      0.039) and 11 false negative results, giving a low sensitivity of 0.62 and a NPV
      of 0.31. For the diagnosis of enterocele, D-MRI was inferior to CD, with five
      false negative results, giving a low sensitivity of 0.17 and high specificity
      (1.0) and PPV (1.0). Nine false positive intussusceptions were seen on D-MRI with
      only two missed. CONCLUSION: The accuracy of D-MRI for diagnosing rectocele and
      enterocele is less than that of CD. D-MRI, however, appears superior to CD in
      identifying intussusception. D-MRI and CD are complementary imaging techniques in
      the evaluation of patients with symptoms of prolapse of the posterior
      compartment.

PMID- 27870168
TI  - Proteome and Secretome Characterization of Glioblastoma-Derived Neural Stem
      Cells.
AB  - Glioblastoma multiforme (GBM) (grade IV astrocytoma) is the most common and
      aggressive primary brain tumor. GBM consists of heterogeneous cell types
      including a subset of stem cell-like cells thought to sustain tumor growth. These
      tumor-initiating glioblastoma multiforme-derived neural stem (GNS) cells as well
      as their genetically normal neural stem (NS) counterparts can be propagated in
      culture as relatively pure populations. Here, we perform quantitative proteomics
      to globally characterize and compare total proteome plus the secreted proteome
      (secretome) between GNS cells and NS cells. Proteins and pathways that
      distinguish malignant cancer (GNS) stem cells from their genetically normal
      counterparts (NS cells) might have value as new biomarkers or therapeutic
      targets. Our analysis identified and quantified ~7,500 proteins in the proteome
      and ~2,000 in the secretome, 447 and 138 of which were differentially expressed,
      respectively. Notable tumor-associated processes identified using gene set
      enrichment analysis included: extracellular matrix interactions, focal adhesion,
      cell motility, and cell signaling. We focused on differentially expressed surface
      proteins, and identified 26 that participate in ligand-receptor pairs that play a
      prominent role in tumorigenesis. Immunocytochemistry and immunoblotting confirmed
      that CD9, a recently identified marker of adult subventricular zone NS cells, was
      consistently enriched across a larger set of primary GNS cell lines. CD9 may,
      therefore, have value as a GNS-specific surface marker and a candidate
      therapeutic target. Altogether, these findings support the notion that increased
      cell-matrix and cell-cell adhesion molecules play a crucial role in promoting the
      tumor initiating and infiltrative properties of GNS cells. Stem Cells 2017;35:967
      980.

PMID- 27870171
TI  - Sciatic nerve block and enhanced recovery after total knee arthroplasty.

PMID- 27870172
TI  - Supraclavicular or interscalene brachial plexus block for rotator cuff repair?

PMID- 27870173
TI  - Apnoeic oxygenation in pregnancy.

PMID- 27870174
TI  - Eye protection in anaesthesia.

PMID- 27870175
TI  - Another cardiopulmonary exercise testing machine fault.

PMID- 27870176
TI  - Cricoid pressure and the law.

PMID- 27870177
TI  - Incidental finding of a tracheal fragment from a Frova intubating catheter.

PMID- 27870178
TI  - Sciatic nerve block and enhanced recovery after total knee arthroplasty - a
      reply.

PMID- 27870179
TI  - Abandoning cricoid pressure - a reply.

PMID- 27870180
TI  - Complete relinquishing of anaesthetic conscientiousness, optimisation and nuance
      (CRAC-ON) trial.

PMID- 27870181
TI  - Interscalene catheters for shoulder surgery.

PMID- 27870182
TI  - Airway topical anaesthesia for awake fibreoptic intubation - a reply.

PMID- 27870183
TI  - AAGBI safe vascular access guidelines - a reply.

PMID- 27870184
TI  - Interscalene catheters for shoulder surgery - a reply.

PMID- 27870186
TI  - Correction.

PMID- 27870185
TI  - Cortical reflex myoclonus.

PMID- 27870187
TI  - Apnoeic oxygenation in pregnancy - a reply.

PMID- 27870188
TI  - A complication of a femoral arterial catheter.

PMID- 27870189
TI  - Comparing fibreoscopy with the Pentax Airway Scope for awake orotracheal
      intubation.

PMID- 27870190
TI  - Is a judicial change needed to protect organ donation?

PMID- 27870191
TI  - A COMMUNITY MENTAL HEALTH PROFESSIONAL DEVELOPMENT MODEL FOR THE EXPANSION OF
      REFLECTIVE PRACTICE AND SUPERVISION: EVALUATION OF A PILOT TRAINING SERIES FOR
      INFANT MENTAL HEALTH PROFESSIONALS.
AB  - The Michigan Association for Infant Mental Health identified a need for
      reflective supervision training for infant mental health (IMH) specialists
      providing home-based services to highly vulnerable infants and their families.
      Findings indicate that this pilot of an IMH community mental health professional
      development model was successful, as measured by the participants' increased
      capacity to apply reflective practice and supervisory knowledge and skills.
      Furthermore, IMH clinicians demonstrated an increase in the frequency of their
      use of reflective practice skills, and their supervisors demonstrated an increase
      in their sense of self-efficacy regarding reflective supervisory tasks. Finally,
      the evaluation included a successful pilot of new measures designed to measure
      reflective practice, contributing to the growing body of research in the area of
      reflective supervision.

PMID- 27870192
TI  - "EFFECTIVE VOLUNTEERISM:" HELPING CHILD CAREGIVERS IN DEVELOPING COUNTRIES.
AB  - This article proposes a method of volunteering mental health consultation to
      child caregivers in developing countries in the context of episodic visits and a
      long-term relationship. It is derived from the author's experience doing this
      work for approximately 12 years. The two foundational features of the method-the
      role of a consultant and a long-term relationship-are described. The method is
      then elaborated in two settings: consultation to caregivers in an orphanage in
      Central America and at a hospital in India. While these examples are distinct in
      multiple domains, they have in common the core features of the consultative model
      and a long-term relationship. Finally, the article briefly addresses challenges
      that the consultant experiences when working with neglected and traumatized
      children and the usefulness of reflective practice. It is hoped that an
      articulation of this method may make it possible for many who might wish to
      volunteer to do so, in a way that neither interferes significantly with their
      work and family life at home nor creates the problems of "helicopter
      volunteering."

PMID- 27870193
TI  - REFLECTION IN HOME VISITING: THE WHAT, WHY, AND A BEGINNING STEP TOWARD HOW.
AB  - The work of home visitors in early childhood fields may include addressing many
      challenges to achieving curricular outcomes, including issues such as maintaining
      boundaries and managing one's own reactions to children, parents, and overall
      family situations. Increasingly, reflective supervision and consultation are
      recognized as a way for workers in home-visiting early intervention and early
      care fields to address these personal and professional challenges and build
      competence (Watson, Gatti, Cox, Harrison, & Hennes, ). The features of home
      visiting that make reflective supervision/consultation essential are discussed.
      Next, results of a pilot project in which a sample of Part C early intervention
      providers respond to a vignette portraying a challenging parent-child interaction
      are briefly presented and discussed. Despite often stating the importance of
      relationships, participants did not identify concrete methods of supporting
      relationship or demonstrate recognition of parallel process. In addition,
      providers seldom endorsed the use of reflective skills such as observing,
      listening, wondering, or reflecting (Weatherston, ), and no providers discussed a
      need for reflective supervision/consultation. We suggest that these findings
      illustrate some of the areas in which early intervention home visitors could
      benefit from participation in reflective supervision/consultation to move from
      identifying reflective skills as important to actually being able to use such
      skills in their work with families.

PMID- 27870195
TI  - Shigella flexneri modulates stress granule composition and inhibits stress
      granule aggregation.

PMID- 27870194
TI  - Gray platelet syndrome: Novel mutations of the NBEAL2 gene.

PMID- 27870196
TI  - Yngve Larsson (1917-2014), a pioneer in the treatment of childhood diabetes.

PMID- 27870197
TI  - The good stress of being born.

PMID- 27870198
TI  - Rolf Zetterstrom (1920-2011), Professor of paediatrics, prolific author and
      editor-in-chief.

PMID- 27870200
TI  - Petter Karlberg (1919-2006), a curious scientist.

PMID- 27870201
TI  - The importance of being earnest in epidemiology.

PMID- 27870202
TI  - Bo Vahlquist (1909-1978), a great paediatrician and friend.

PMID- 27870203
TI  - Isak Jundell (1867-1945), Professor of paediatrics, founder of Acta Paediatrica
      and the child's best friend.

PMID- 27870204
TI  - Bengt Hagberg (1923-2015), Swedish father of child neurology.

PMID- 27870205
TI  - Acta Paediatrica from Print (1921-2016) to Online only.

PMID- 27870206
TI  - Antibiotics are being misused to treat diarrhoeal disease in children in Central
      Asia.

PMID- 27870207
TI  - Tony Foucard (1936-2008), a man of honour.

PMID- 27870208
TI  - Carl-Gustaf Bergstrand (1914-2011), former Managing Editor of Acta Paediatrica.

PMID- 27870209
TI  - The rise of the growth hormone era from a Swedish perspective.

PMID- 27870210
TI  - Risk profiles for haemolytic and nonhaemolytic neonatal jaundice.

PMID- 27870211
TI  - A multicellular organism with embedded cell clusters from the Ediacaran Weng'an
      biota (Doushantuo Formation, South China).
AB  - Three-dimensional analyses of the early Ediacaran microfossils from the Weng'an
      biota (Doushantuo Formation) have focused predominantly on multicellular forms
      that have been interpreted as embryos, and yet they have defied phylogenetic
      interpretation principally because of absence of evidence from other stages in
      their life cycle. It is therefore unfortunate that the affinities of the various
      other Doushantuo microfossils have been neglected. A new conical fossil that is
      preserved at a cellular level is described here. The fossil contains distinct
      cell clusters that are characterized and analysed in three dimensions. These
      clusters are often exposed at the specimen surface, and the fossil preserves many
      hemispherical craters that are interpreted as positions where clusters have left
      the organism. The cell clusters may be either reproductive propagules or
      infesting organisms. Similar clusters are found in a variety of Doushantuo
      organisms including putative animal embryos and algae.

PMID- 27870213
TI  - Unexpected sex-specific post-reproductive lifespan in the free-living nematode
      Pristionchus exspectatus.
AB  - Patterns of senescence (or aging) can vary among life history traits and between
      the sexes, providing an opportunity to study variation in the aging process
      within a single species. We previously found that females of the nematode
      Pristionchus exspectatus outlive males by a substantial margin under laboratory
      conditions. Here, we show that sex-specific reproductive senescence unfolds in
      the opposite direction in this species, resulting in a prolonged period of female
      specific post-reproductive survival: females lost the ability to reproduce at
      approximately 4.7 weeks despite a median lifespan of about 12.3 weeks under lab
      conditions, whereas males lost the ability to reproduce at approximately 6.6
      weeks, roughly in line with their median lifespan of around 7.6 weeks.
      Interestingly, somatic senescence (declining crawling speed) only explained
      reproductive senescence in males, whereas females lost the ability to reproduce
      regardless of condition. However, we found that housing females with males
      significantly increased their mortality rate, indicating that female-specific
      post-reproductive survival is unlikely to occur in the wild. We discuss our
      results in light of evolutionary theories of post-reproductive survival and
      previous studies of nematode behavioral ecology, arguing that premature
      reproductive senescence may stem from sex-specific condition-dependent survival
      during the reproductive period. Given the proven lab tractability of Prisitonchus
      nematodes, our findings provide a foundation for integrative research that
      combines evolutionary ecology and molecular genetics in the study of sex-specific
      senescence and post-reproductive survival.

PMID- 27870212
TI  - Ancestral androgenic differentiation pathways are repurposed during the evolution
      of adult sexual plasticity.
AB  - Although early exposure to androgens is necessary to permanently organize male
      phenotype in many vertebrates, animals that exhibit adult sexual plasticity
      require mechanisms that prevent early fixation of genital morphology and allow
      for genital morphogenesis during adult transformation. In Lythrypnus dalli, a
      teleost fish that exhibits bi-directional sex change, adults display dimorphic
      genitalia morphology despite the absence of sex differences in the potent fish
      androgen 11-ketotestosterone. Based on conserved patterns of vertebrate
      development, two steroid-based mechanisms may regulate the early development and
      adult maintenance of dimorphic genitalia; local androgen receptor (AR) and
      steroidogenic enzyme expression. Consistent with the ancestral pattern of AR
      expression during the multipotential phase of differentiation, juvenile
      differentiation into either sex involved high mesenchymal AR expression. In
      adults, AR expression was high throughout the male genitalia, but low or absent
      in females. Consistent with the hypothesis that adult sexual plasticity
      repurposes pathways from primary differentiation, we show that adults with
      transitioning genitalia also exhibited higher AR expression relative to females.
      Local androgen biosynthesis may also participate in genitalia transformation, as
      transitioning adults had greater 11beta-HSD-like immunoreactivity in the
      epithelial layer of the dorsal lumen compared to both sexes. By administering an
      AR antagonist to adult males, we show AR is necessary to maintain male-typical
      morphology. In a species that is resistant to early sexual canalization, early
      androgenic differentiation mechanisms are consistent with other vertebrates and
      the tissue-specific regulation of AR expression appears to be repurposed in
      adulthood to allow for transitions between sexual phenotypes.

PMID- 27870214
TI  - Furling the flags in evolution.

PMID- 27870217
TI  - A Message from the Organizing Committee.

PMID- 27870220
TI  - Keynote Speakers.

PMID- 27870218
TI  - POSTER PRESENTATION.

PMID- 27870215
TI  - Detangling the evolutionary developmental integration of dentate jaws: evidence
      that a p63 gene network regulates odontogenesis exclusive of mandible
      morphogenesis.
AB  - Vertebrate jaws and dentitions fit and function together, yet the genetic
      processes that coordinate cranial and dental morphogenesis and evolution remain
      poorly understood. Teeth but not jaws fail to form in the edentate p63-/- mouse
      mutant, which we used here to identify genes important to odontogenesis, but not
      jaw morphogenesis, and that may allow dentitions to change during development and
      evolution without necessarily affecting the jaw skeleton. With the working
      hypothesis that tooth and jaw development are autonomously controlled by discreet
      gene regulatory networks, using gene expression microarray assays validated by
      quantitative reverse-transcription PCR we contrasted expression in mandibular
      prominences at embryonic days (E) 10-13 of mice with normal lower jaw development
      but either normal (p63+/- , p63+/+ ) or arrested (p63-/- ) tooth development. The
      p63-/- mice showed significantly different expression (fold change >=2, <=-2; P
      <= 0.05) of several genes. Some of these are known to help regulate odontogenesis
      (e.g., p63, Osr2, Cldn3/4) and/or to be targets of p63 (e.g., Jag1/2, Fgfr2);
      other genes have no previously reported roles in odontogenesis or the p63 pathway
      (e.g., Fermt1, Cbln1, Pltp, Krt8). As expected, from E10 to E13, few genes known
      to regulate mandible morphogenesis differed in expression between mouse strains.
      This study newly links several genes to odontogenesis and/or to the p63 signaling
      network. We propose that these genes act in a novel odontogenic network that is
      exclusive of lower jaw morphogenesis, and posit that this network evolved in
      oral, not pharyngeal, teeth.

PMID- 27870225
TI  - Reducing HIV incidence using anti-retrovirals: Imperative and achievable.

PMID- 27870221
TI  - Inductors and regulatory properties of the genomic island-associated fru2
      metabolic operon of Streptococcus agalactiae.
AB  - The fru2 metabolic operon of Streptococcus agalactiae encodes the
      phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) enzyme II
      complex Fru2 (EIIBFru2 , EIIAFru2 , and EIICFru2 ); Fru2 R, a transcriptional
      activator with PTS regulatory domains (PRDs); a d-allulose-6-phosphate 3
      epimerase; a transaldolase; and a transketolase. We showed that the transcription
      of fru2 is induced during the stationary phase of growth in complex media and
      during incubation in human cerebrospinal or amniotic fluids. d-allose and d
      ribose are environmental signals governing this induction. PTSFru2 is involved in
      the activation of the fru2 promoter, and the histidine-67 of EIIAFru2 and the
      cysteine-9 of EIIBFru2 are important for this function. The activation of fru2 is
      also controlled by Fru2 R. The histidine-243 in the PRD1 domain, the histidine
      323 in the PRD2 domain, the cysteine-400 in the EIIB-like domain, and the
      histidine-549 in the EIIA-like domain are important for the function of Fru2 R.
      Fru2 R binds to a DNA region containing palindromic sequences upstream of the
      identified transcriptional start site. EIIBFru2 interacts physically with the C
      terminal part of Fru2 R (expressing the EIIB-like and EIIA-like motifs) and with
      EIIAFru2 . We propose a model of regulation of fru2 depending on the presence of
      an activatory carbohydrate in the growth medium.

PMID- 27870228
TI  - Dialysate bacterial endotoxin as a prognostic indicator of peritoneal dialysis
      related peritonitis.
AB  - Peritonitis is the major complication of peritoneal dialysis (PD). The aim of our
      present study is to explore the prognostic value of endotoxin level in PD
      effluent for the prediction of treatment failure in PD-related peritonitis. We
      studied 325 peritonitis episodes in 223 patients. PD effluent (PDE) was collected
      every 5 days for endotoxin level and leukocyte count. Patients were followed for
      relapsing or recurrent peritonitis. We found 20 episodes (6.2%) had primary
      treatment failure; 41 (12.6%) developed relapsing, 19 (5.8%) had recurrent, and
      22 (6.8%) had repeat episodes. Endotoxin was detectable in the PDE of 19 episodes
      (24.4%) caused by Gram negative organisms, 4 episodes (6.8%) of mixed bacterial
      growth, and none of the culture negative episodes or those by Gram positive
      organisms. For episodes caused by Gram negative bacteria, a detectable endotoxin
      level in PDE on day 5 had a sensitivity and specificity of 66.7% and 83.3%,
      respectively, for predicting primary treatment failure. In contrast, PDE
      leukocyte count > 1000 per mm3 on day 5 had a sensitivity and specificity of
      88.9% and 89.1%, respectively; the addition of PDE endotoxin assay did not
      improve the sensitivity or specificity. We conclude that detectable endotoxin in
      PDE 5 days after antibiotic therapy might predict primary treatment failure in
      peritonitis episodes caused by Gram negative organisms. However, the sensitivity
      and specificity of PDE endotoxin assay was inferior to PDE leukocyte count.

PMID- 27870230
TI  - Impact of low-density lipoprotein apheresis for nephrotic syndrome in a patient
      with immunoglobulin M nephropathy.

PMID- 27870229
TI  - Remitting Seronegative Symmetrical Synovitis with Pitting Oedema (RS3PE) Syndrome
      in a Chronic Kidney Disease Patient Undzergoing Haemodialysis.

PMID- 27870233
TI  - Reflections on a year at Diabetic Medicine.

PMID- 27870227
TI  - Aspergillosis and the role of mucins in cystic fibrosis.
AB  - The prevalence of aspergillosis in CF patients has until recently been
      underestimated, but increasing evidence suggests that it may play an important
      role in the progression of CF lung disease. In healthy airways, Aspergillus
      fumigatus can be efficiently removed from the lung by mechanisms such as
      mucociliary clearance and cough. However, these mechanisms are defective in CF,
      allowing pathogens such as A. fumigatus to germinate and establish chronic
      infections within the airways. The precise means by which A. fumigatus
      contributes to CF lung disease remain largely unclear. As the first point of
      contact within the lung, and an important component of the innate immune system,
      it is likely that the mucus barrier plays an important role in this process.
      Study of the functional interplay between this vital protective barrier, and in
      particular its principal structural components, the polymeric gel-forming mucins,
      and CF pathogens such as A. fumigatus, is at an early stage. A. fumigatus
      protease activity has been shown to upregulate mucus production by inducing mucin
      mRNA and protein expression, and A. fumigatus proteases and glycosidases are able
      to degrade mucins. This may allow A. fumigatus to alter mucus barrier properties
      to promote fungal colonization of the airways and/or utilize mucins as a nutrient
      source. Moreover, conidial surface lectin binding to mucin glycans is a key
      aspect of clearance of Aspergillus from the lung in health but may be an
      important aspect of colonization, where mucociliary clearance is compromised, as
      in the CF lung. Here we discuss the nature of the mucus barrier and its mucin
      components in CF, and how they may be implicated in A. fumigatus infection.
      Pediatr Pulmonol 2017;52:548-555. (c) 2016 The Authors. Pediatric Pulmonology.
      Published by Wiley Periodicals, Inc.

PMID- 27870231
TI  - Progressive idiopathic nodular glomerulosclerosis mimicking diabetic nephropathy
      without abnormal glycemic metabolism.

PMID- 27870234
TI  - The 2016 Hugo Schindelka Medal and Lecture awarded to Professor David H. Lloyd.

PMID- 27870235
TI  - Efficacy and duration of action of oral fluralaner and spot-on
      moxidectin/imidacloprid in cats infested with Lynxacarus radovskyi.
AB  - BACKGROUND: Lynxacarus radovskyi has been observed in cats in Malaysia;
      previously treatment with fipronil and moxidectin/imidacloprid spot-on has been
      described. OBJECTIVES: To compare the efficacy of two spot-on treatments of
      moxidectin/imidacloprid, two weeks apart to a single oral dose of fluralaner
      against Lynxacarus radovskyi and evaluate time to re-infestation. METHODS: Thirty
      cats were assigned to three groups of ten cats each. Group 1 received one 250 mg
      fluralaner tablet. Group 2 received two doses of moxidectin/imidacloprid spot-on
      two weeks apart. Group 3 consisted of untreated controls. For each cat, three
      plucks of about 50 hairs each were collected from three sites (dorsal neck,
      lateral thigh and perineal/tail region) for a total of nine pluckings every two
      weeks. Severity of infestation was scored from 0 (no parasite), to 1 (only
      nonhatched eggs), 2 (both hatched and nonhatched eggs), 3 (<50 mites) and 4 (>50
      mites). Efficacy was compared between treatment groups and over time in the same
      group, and results analysed statistically. Re-infestation was defined as the
      identification of new eggs or mites on hair pluckings. RESULTS:
      Moxidectin/imidacloprid spot-on and oral fluralaner achieved 100% eradication
      within 28 days. No significant difference was observed between groups 1 and 2; re
      infestation occurred by Day 56 in both treatment groups. CONCLUSION: A single
      dose of oral fluralaner or two moxidectin/imidacloprid spot-on treatments two
      weeks apart are efficacious in the eradication of L. radovskyi in cats and able
      to prevent re-infestation for at least 42 days post-treatment.

PMID- 27870237
TI  - 5th Strasbourg Summer School in Chemoinformatics.

PMID- 27870236
TI  - Prior antimicrobial use as a risk factor for resistance in selected
      Staphylococcus pseudintermedius isolates from the skin and ears of dogs.
AB  - BACKGROUND: Antimicrobial resistance within bacteria continues to present
      therapeutic challenges. One presumed risk factor for increased rates of
      resistance is prior exposure to antimicrobial drugs. OBJECTIVES: To examine the
      impact of time since most recent exposure, the number of prior antimicrobial
      exposures and duration of use on antimicrobial resistance rates in Staphylococcus
      pseudintermedius isolates. METHODS: Inclusion of a case in the study required
      laboratory isolation of S. pseudintermedius from a clinical specimen.
      Antibiograms and information regarding prior antimicrobial exposures were
      extracted from the medical records of dogs diagnosed with pyoderma or otitis
      externa. RESULTS: Meticillin resistance (MR) was identified in 48.1% of isolates.
      Recent use of beta-lactam antimicrobials was associated with increased odds of
      resistance to meticillin (P < 0.001) and fluoroquinolones (P < 0.001).
      Antimicrobial therapy within 1 month prior to sampling was also associated with
      MR (60.7%; P = 0.009) and multidrug resistance (61.9%; P = 0.029). The number of
      prior exposures to beta-lactams or fluoroquinolones were associated with
      resistance to these same classes (P = 0.001 and 0.02, respectively) and to other
      antimicrobial classes (P = 0.016 for resistance to fluoroquinolones following
      treatment with beta-lactams and P = 0.015 for MR following treatment with
      fluoroquinolones). Longer treatment duration with beta-lactam drugs was
      associated with higher proportion of MR (P = 0.004). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Treatment based upon culture and susceptibility testing is highly
      recommended for dogs that have received multiple antimicrobial drug exposures or
      that were treated within the preceding month. This may be especially important
      when the prior therapeutic regimen included a drug from the beta-lactam or
      fluoroquinolone classes.

PMID- 27870238
TI  - Building Compound Archives for the Future.
AB  - Will the targets of the future be covered by the compound libraries of today?
      This communication will cover a critical review of past strategies before turning
      to a new measure of diversity, protein pockets. A fingerprint descriptor for
      pockets will be described.

PMID- 27870239
TI  - Soft Sensors: Chemoinformatic Model for Efficient Control and Operation in
      Chemical Plants.
AB  - Soft sensor is statistical model as an essential tool for controlling
      pharmaceutical, chemical and industrial plants. I introduce soft sensor, the
      roles, the applications, the problems and the research examples such as adaptive
      soft sensor, database monitoring and efficient process control. The use of soft
      sensor enables chemical industrial plants to be operated more effectively and
      stably.

PMID- 27870240
TI  - Analyzing Promiscuity at the Level of Active Compounds and Targets.
AB  - In the context of polypharmacology, promiscuity is defined as the ability of
      small molecules to specifically interact with multiple targets. In addition,
      promiscuity can also be viewed as a characteristic feature of targets by
      considering their ability to recognize structurally diverse molecules as well as
      compounds with multi-target activities. Promiscuity estimates can be obtained
      through systematic mining of compound activity data. Currently available volumes
      of activity data are so large that it should be possible to derive statistically
      sound trends from their analysis. However, confidence criteria must be carefully
      considered when drawing conclusions from compound data mining. Herein, the
      results of recent promiscuity analyses are presented in context, including
      studies that view promiscuity from a target perspective.

PMID- 27870241
TI  - Multiple-parameter Optimization in Drug Discovery: Example of the 5-HT1B GPCR.
AB  - Early phase drug discovery is a multi-parameter optimisation process. Finding
      drugable targets, discovering starting points for lead optimisation and creating
      novel structures with new biological properties within these constraints is
      challenging. As an example of a drug optimisation strategy, recent work on 5-HT1B
      antagonists will be described. This is put in the context of the drugability of
      the target, the desired physicochemical properties of the desired molecules and
      approaches to compound design to create high affinity, selective molecules that
      are optimised to have low Central Nervous System (CNS) penetration.

PMID- 27870242
TI  - Explorations into Chemical Reactions and Biochemical Pathways.
AB  - A brief overview of the work in the research group of the present author on
      extracting knowledge from chemical reaction data is presented. Methods have been
      developed to calculate physicochemical effects at the reaction site. It is shown
      that these physicochemical effects can quite favourably be used to derive
      equations for the calculation of data on gas phase reactions and on reactions in
      solution such as aqueous acidity of alcohols or carboxylic acids or the
      hydrolysis of amides. Furthermore, it is shown that these physicochemical effects
      are quite effective for assigning reactions into reaction classes that correspond
      to chemical knowledge. Biochemical reactions constitute a particularly
      interesting and challenging task for increasing our understanding of living
      species. The BioPath.Database is a rich source of information on biochemical
      reactions and has been used for a variety of applications of chemical,
      biological, or medicinal interests. Thus, it was shown that biochemical reactions
      can be assigned by the physicochemical effects into classes that correspond to
      the classification of enzymes by the EC numbers. Furthermore, 3D models of
      reaction intermediates can be used for searching for novel enzyme inhibitors. It
      was shown in a combined application of chemoinformatics and bioinformatics that
      essential pathways of diseases can be uncovered. Furthermore, a study showed that
      bacterial flavor-forming pathways can be discovered.

PMID- 27870243
TI  - Empirical Scoring Functions for Affinity Prediction of Protein-ligand Complexes.
AB  - The ability to rapidly assess the quality of a protein-ligand complex in terms of
      its affinity is of fundamental importance for various methods of computer-aided
      drug design. While simple filtering or matching critieria may be sufficient in
      fast docking methods or at early stages of virtual screening, estimates of the
      actual free energy of binding are needed whenever refined docking solutions,
      ligand rankings or support for the optimization of hit compounds are required. If
      rigorous free energy calculations based on molecular simulations are impractical,
      such affinity estimates are provided by scoring functions. The class of empirical
      scoring functions aims to provide them via a regression-based approach. Using
      experimental structures and affinity data of protein-ligand complexes and
      descriptors suitable to capture the essential features of the interaction, these
      functions are trained with classical linear regression techniques or machine
      learning methods. The latter have led to considerable improvements in terms of
      prediction accuracy for large generic data sets. Nevertheless, many limitations
      are not yet resolved and pose significant challenges for future developments.

PMID- 27870244
TI  - Visualization Based Data Mining for Comparison Between Two Solar Cell Libraries.
AB  - Material informatics may provide meaningful insights and powerful predictions for
      the development of new and efficient Metal Oxide (MO) based solar cells. The main
      objective of this paper is to establish the usefulness of data reduction and
      visualization methods for analyzing data sets emerging from multiple all-MOs
      solar cell libraries. For this purpose, two libraries, TiO2 |Co3 O4 and TiO2 |Co3
      O4 |MoO3 , differing only by the presence of a MoO3 layer in the latter were
      analyzed with Principal Component Analysis and Self-Organizing Maps. Both
      analyses suggest that the addition of the MoO3 layer to the TiO2 |Co3 O4 library
      has affected the overall photovoltaic (PV) activity profile of the solar cells
      making the two libraries clearly distinguishable from one another. Furthermore,
      while MoO3 had an overall favorable effect on PV parameters, a sub-population of
      cells was identified which were either indifferent to its presence or even
      demonstrated a reduction in several parameters.

PMID- 27870245
TI  - The Art of Compiling Protein Binding Site Ensembles.
AB  - Structure-based drug design starts with the collection, preparation, and initial
      analysis of protein structures. With more than 115,000 structures publically
      available in the Protein Data Bank (PDB), fully automated processes reliably
      performing these important preprocessing steps are needed. Several tools are
      available for these tasks, however, most of them do not address the special needs
      of scientists interested in protein-ligand interactions. In this paper, we
      summarize our research activities towards an automated processing pipeline from
      raw PDB data towards ready-to-use protein binding site ensembles. Starting from a
      single protein structure, the pipeline covers the following phases: Extracting
      structurally related binding sites from the PDB, aligning disconnected binding
      site sequences, resolving tautomeric forms and protonation, orienting hydrogens
      and flippable side-chains, structurally aligning the multitude of binding sites,
      and performing a reasonable reduction of ensemble structures. The pipeline, named
      SIENA, creates protein-structural ensembles for the analysis of protein
      flexibility, molecular design efforts like docking or de novo design within
      seconds. For the first time, we are able to process the whole PDB in order to
      create a large collection of protein binding site ensembles. SIENA is available
      as part of the ZBH ProteinsPlus webserver under http://proteinsplus.zbh.uni
      hamburg.de.

PMID- 27870247
TI  - Sparse Neural Network Models of Antimicrobial Peptide-Activity Relationships.
AB  - We present an adaptive neural network model for chemical data classification. The
      method uses an evolutionary algorithm for optimizing the network structure by
      seeking sparsely connected architectures. The number of hidden layers, the number
      of neurons in each layer and their connectivity are free variables of the system.
      We used the method for predicting antimicrobial peptide activity from the amino
      acid sequence. Visualization of the evolved sparse network structures suggested a
      high charge density and a low aggregation potential in solution as beneficial for
      antimicrobial activity. However, different training data sets and peptide
      representations resulted in greatly varying network structures. Overall, the
      sparse network models turned out to be less accurate than fully-connected
      networks. In a prospective application, we synthesized and tested 10 de novo
      generated peptides that were predicted to either possess antimicrobial activity,
      or to be inactive. Two of the predicted antibacterial peptides showed cosiderable
      bacteriostatic effects against both Staphylococcus aureus and Escherichia coli.
      None of the predicted inactive peptides possessed antibacterial properties.
      Molecular dynamics simulations of selected peptide structures in water and TFE
      suggest a pronounced peptide helicity in a hydrophobic environment. The results
      of this study underscore the applicability of neural networks for guiding the
      computer-assisted design of new peptides with desired properties.

PMID- 27870246
TI  - Materials Informatics: Statistical Modeling in Material Science.
AB  - Material informatics is engaged with the application of informatic principles to
      materials science in order to assist in the discovery and development of new
      materials. Central to the field is the application of data mining techniques and
      in particular machine learning approaches, often referred to as Quantitative
      Structure Activity Relationship (QSAR) modeling, to derive predictive models for
      a variety of materials-related "activities". Such models can accelerate the
      development of new materials with favorable properties and provide insight into
      the factors governing these properties. Here we provide a comparison between
      medicinal chemistry/drug design and materials-related QSAR modeling and highlight
      the importance of developing new, materials-specific descriptors. We survey some
      of the most recent QSAR models developed in materials science with focus on
      energetic materials and on solar cells. Finally we present new examples of
      material-informatic analyses of solar cells libraries produced from metal oxides
      using combinatorial material synthesis. Different analyses lead to interesting
      physical insights as well as to the design of new cells with potentially improved
      photovoltaic parameters.

PMID- 27870249
TI  - Ethical Issues in Health Systems Research in Low and Middle-Income Countries.

PMID- 27870250
TI  - New insights into interactions between the nucleotide-binding domain of CFTR and
      keratin 8.
AB  - The intermediate filament protein keratin 8 (K8) interacts with the nucleotide
      binding domain 1 (NBD1) of the cystic fibrosis (CF) transmembrane regulator
      (CFTR) with phenylalanine 508 deletion (DeltaF508), and this interaction hampers
      the biogenesis of functional DeltaF508-CFTR and its insertion into the plasma
      membrane. Interruption of this interaction may constitute a new therapeutic
      target for CF patients bearing the DeltaF508 mutation. Here, we aimed to
      determine the binding surface between these two proteins, to facilitate the
      design of the interaction inhibitors. To identify the NBD1 fragments perturbed by
      the DeltaF508 mutation, we used hydrogen-deuterium exchange coupled with mass
      spectrometry (HDX-MS) on recombinant wild-type (wt) NBD1 and DeltaF508-NBD1 of
      CFTR. We then performed the same analysis in the presence of a peptide from the
      K8 head domain, and extended this investigation using bioinformatics procedures
      and surface plasmon resonance, which revealed regions affected by the peptide
      binding in both wt-NBD1 and DeltaF508-NBD1. Finally, we performed HDX-MS analysis
      of the NBD1 molecules and full-length K8, revealing hydrogen-bonding network
      changes accompanying complex formation. In conclusion, we have localized a region
      in the head segment of K8 that participates in its binding to NBD1. Our data also
      confirm the stronger binding of K8 to DeltaF508-NBD1, which is supported by an
      additional binding site located in the vicinity of the DeltaF508 mutation in
      NBD1.

PMID- 27870252
TI  - Amine-Directed Hydrogen-Bonded Two-Dimensional Supramolecular Structures.
AB  - Utilizing pure amine hydrogen bonding is a novel approach for constructing two
      dimensional (2D) networks. Further, such systems are capable of undergoing
      structural modifications due to changes in pH. In this study, we designed a 2D
      network of triaminobenzene (TAB) molecules that by varying the pH from neutral to
      acidic, form either ordered or disordered structures on Au(111) surface as
      revealed in scanning tunneling microscopy images. In near-neutral solution (pH
      ~5.5), protonation of TAB generates charged species capable of forming H-bonds
      between amine groups of neighboring molecules resulting in the formation of a 2D
      supramolecular structure on the electrified surface. At lower pH, due to the
      protonation of the amine groups, intermolecular hydrogen bonding is no longer
      possible and no ordered structure is observed on the surface. This opens the
      possibility to employ pH as a chemical trigger to induce a phase transition in
      the 2D molecular network of triaminobenzene molecules.

PMID- 27870253
TI  - Spotlights on our sister journals: ChemPhysChem 21/2016.

PMID- 27870251
TI  - Concise Review: Getting to the Core of Inherited Bone Marrow Failures.
AB  - Bone marrow failure syndromes (BMFS) are a group of disorders with complex
      pathophysiology characterized by a common phenotype of peripheral cytopenia
      and/or hypoplastic bone marrow. Understanding genetic factors contributing to the
      pathophysiology of BMFS has enabled the identification of causative genes and
      development of diagnostic tests. To date more than 40 mutations in genes involved
      in maintenance of genomic stability, DNA repair, ribosome and telomere biology
      have been identified. In addition, pathophysiological studies have provided
      insights into several biological pathways leading to the characterization of
      genotype/phenotype correlations as well as the development of diagnostic
      approaches and management strategies. Recent developments in bone marrow
      transplant techniques and the choice of conditioning regimens have helped improve
      transplant outcomes. However, current morbidity and mortality remain unacceptable
      underlining the need for further research in this area. Studies in mice have
      largely been unable to mimic disease phenotype in humans due to difficulties in
      fully replicating the human mutations and the differences between mouse and human
      cells with regard to telomere length regulation, processing of reactive oxygen
      species and lifespan. Recent advances in induced pluripotency have provided novel
      insights into disease pathogenesis and have generated excellent platforms for
      identifying signaling pathways and functional mapping of haplo-insufficient genes
      involved in large-scale chromosomal deletions-associated disorders. In this
      review, we have summarized the current state of knowledge in the field of BMFS
      with specific focus on modeling the inherited forms and how to best utilize these
      models for the development of targeted therapies. Stem Cells 2017;35:284-298.

PMID- 27870255
TI  - Now that is a game changer: The entire reproductive cycle of an oocyte in a dish.

PMID- 27870254
TI  - A national patient and public colorectal research agenda: integration of consumer
      perspectives in bowel disease through early consultation.
AB  - AIM: There is a recognized need to include the views of patients and the public
      in prioritizing health research. This study aimed: (i) to explore patients' views
      on colorectal research; and (ii) to prioritize research topics with patients and
      the public. METHOD: In phase 1, 12 charitable organizations and patient groups
      with an interest in bowel disease were invited to attend a consultation exercise.
      Participants were briefed on 25 colorectal research topics prioritized by members
      of the Association of Coloproctology of Great Britain and Ireland. Focus groups
      were conducted and discussions were recorded with field notes. Analysis was
      conducted using principles of thematic analysis. In phase 2, a free public
      consultation was undertaken. Participants were recruited from newspaper
      advertisements, were briefed on the same research topics and were asked to rate
      the importance of each on a five-point Likert scale. Descriptive statistics were
      used to rank the topics. Univariable linear regression compared recorded
      demographic details with mean topic scores. RESULTS: Focus groups were attended
      by 12 patients who highlighted the importance of patient-centred information for
      trial recruitment and when selecting outcome measures. Some 360 people attended
      the public consultation, of whom 277 (77%) were recruited. Participants rated
      'What is the best way to treat early cancer in the back passage?' highest, with
      227 (85%) scoring it 4 or 5. There was no correlation between participant
      demographics and mean topic scores. CONCLUSION: The present study prioritized a
      colorectal research agenda with the input of patients and the public. Further
      research is required to translate this agenda into real improvements in patient
      care.

PMID- 27870256
TI  - Factors related to a decline in upper extremity function among patients with a
      wrist fracture due to a fall.
AB  - AIMS: The aim of this study was to identify factors related to a decline in
      function following a wrist fracture. METHODS: Observational, prospective cohort
      study done in five public hospitals of the Basque Health Service. We recruited
      adults aged 65 or older with a wrist fracture due to a fall who attended the
      emergency department (ED) of one of these hospitals. Sociodemographic and
      clinical data were collected, along with information about health-related quality
      of life (HRQoL) and functionality. RESULTS: A decline in function 6 months after
      the fracture was more likely among women (OR=3.409; 95% CI=1.920-6.053), patients
      receiving institutional help before the fracture (OR=5.717; 95% CI=1.644-19.883),
      patients who developed fracture-related complications within 6 months of the fall
      (OR=5.015; 95% CI=1.377-18.268), patients who visited an ED within 6 months of
      the fall (OR=1.646; 95% CI=1.058-2.561), patients with a displaced fracture
      (OR=1.595; 95% CI=1.106-2.300), and patients who broke the dominant hand
      (OR=1.464; 95% CI=1.019-2.103). Better baseline HRQoL and function were
      associated with smaller declines in function 6 months after the fall. Eighteen
      months after the fall, decline in function was more likely among women (OR=2.172;
      95% CI=1.138-4.144) and patients visiting an ED because of fracture-related
      complications (OR=1.722; 95% CI=1.113-2.663). Better HRQoL and dependency level
      at baseline were associated with less decline in function 18 months after the
      fracture. DISCUSSION: Two different models identified several parameters related
      to declines in upper extremity function 6 and 18 months after the fracture.
      CONCLUSIONS: These results can help develop preventive actions needed to avoid or
      reduce the consequences of these falls.

PMID- 27870258
TI  - When data are scarce, model validation should be efficient: Letter Re: Dolera
      Moreno C, Palazon-Bru A, Colomina-Climent F, Gil-Guillen VF. Construction and
      internal validation of a new mortality risk score for patients admitted to the
      intensive care unit. Int J Clin Pract 2016; 10.1111/ijcp.12851.

PMID- 27870257
TI  - Higher levels of apomorphine and rotigotine prescribing reduce overall secondary
      healthcare costs in Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) affects around 100,000 people in England. A
      number of non-oral therapies can improve both the quality of life and reduce
      patient needs for health and social care. However, these can be relatively
      expensive at L2000-L10,000 per year per patient. Our aim was to examine how
      prescribing of these agents relates to secondary care costs. METHODS: Using
      practice level primary care prescribing data and hospital episode statistical
      data in England, we investigated the relation between general practitioner
      prescriptions of apomorphine injections/rotigotine patches and the secondary care
      costs accrued for their diagnosed PD patients for 2011-2014. The median age of
      the PD patients was 78 years. RESULTS: In the period 2011-2014, 58% of the
      average annual L437 million secondary care costs for PD patients came from non
      elective admissions. 80% of this came from seven Healthcare Resource Group
      Chapters linked to PD comorbidities. Compared with practices not using non-oral
      therapies, practices prescribing Apomorphine saved L897 per year per patient of
      secondary care costs to offset the average additional prescribing cost of L475
      per overall patient per year. For Rotigotine, saving was L718 per year per
      patient of secondary care costs offsetting L137 prescribing cost. Practices in
      the highest quartile of non-oral prescribing were using non-oral agents in up to
      28% of their PD patients. CONCLUSIONS: Those practices which used more non-oral
      therapies appear to incur less secondary care costs. A total of 70% of the
      advanced PD patients are not being given access to non-oral treatment. This is a
      challenge for all physicians looking after the older patient.

PMID- 27870259
TI  - Open researcher and contributor ID: ORCID now mandatory for Wiley journals.

PMID- 27870260
TI  - An update to the internal validation of the new mortality risk score for patients
      admitted to the intensive care unit.

PMID- 27870261
TI  - Surface Electrochemical Modification of a Nickel Substrate to Prepare a NiFe
      based Electrode for Water Oxidation.
AB  - The slow kinetics of water oxidation greatly jeopardizes the efficiency of water
      electrolysis for H2 production. Developing highly active water oxidation
      electrodes with affordable fabrication costs is thus of great importance. Herein,
      a NiII FeIII surface species on Ni metal substrate was generated by
      electrochemical modification of Ni in a ferrous solution by a fast, simple, and
      cost-effective procedure. In the prepared NiII FeIII catalyst film, FeIII was
      incorporated uniformly through controlled oxidation of FeII cations on the
      electrode surface. The catalytically active NiII originated from the Ni foam
      substrate, which ensured the close contact between the catalyst and the support
      toward improved charge-transfer efficiency. The as-prepared electrode exhibited
      high activity and long-term stability for electrocatalytic water oxidation. The
      overpotentials required to reach water oxidation current densities of 50, 100,
      and 500 mA cm-2 are 276, 290, and 329 mV, respectively.

PMID- 27870263
TI  - Coevolution, local adaptation and ecological speciation.
AB  - Coevolution is one of the major processes organizing the earth's biodiversity,
      but it remains unclear when and how it may generate species diversity. The study
      by Parchman et al. () in this issue of Molecular Ecology provides the clearest
      evidence to date that divergent local adaptation in a coevolving interaction may
      lead to speciation on one side of an interaction but not necessarily on the other
      side. Red crossbills in North America have diversified into ecotypes that
      specialize on different conifer species, use different calls and vary in the
      extent to which they are nomadic or sedentary. This new study evaluated genomic
      divergence among nine crossbill ecotypes. The authors found low overall genomic
      divergence among many of the ecotypes, but the sedentary South Hills crossbills,
      which are specialized to eat the seeds of a unique population of lodgepole pines,
      showed substantial divergence from other crossbills at a small number of genomic
      regions. These results corroborate past studies showing local coadaptation of the
      morphological traits of South Hills crossbills and lodgepole pines, and premating
      isolation of the South Hills crossbills from other populations. Together, the
      past and new results suggest that local coevolution with lodgepole pines has led
      to reduced gene flow between South Hills crossbills and other crossbills.

PMID- 27870262
TI  - The role of base excision repair in pathogenesis of breast cancer in the Polish
      population.
AB  - Breast cancer (BC) is leading type of cancer among group of women, which
      determines almost 23% of invasive cancers. It has been reported repeatedly that
      the level of oxidative stress is higher for BC in comparison to cancer-free
      woman. The goal of the present study was to evaluate the role of base excision
      repair (BER) pathway in the development of BC. One-hundred seventy-one women with
      confirmed BC and 222 healthy controls were enrolled in presented study. The level
      of oxidative DNA damage and the kinetic of their repair were analyzed by the
      modified alkaline comet assay. The efficiency of BER pathway was evaluated by BER
      assay. The presence of the 326Cys/Cys genotype and 326Cys allele of OGG1 gene and
      the 324His/His of MUTYH gene are associated with increased risk of BC
      development. Moreover, correlation between clinical parameter with selected genes
      has shown increased risk of BC progression. The survival analysis has shown a
      significant lower DFS for individuals with the 762Ala/Ala genotype compared to
      762Val/Vla carriers and the 762Val/Ala genotype in relation to concomitant
      chemotherapy and radiotherapy. In subgroup of patients with alone chemotherapy
      and alone radiotherapy, the 762Val/Val genotype was significantly associated with
      lower overall survival. Furthermore, we also elevated the level of basal and
      oxidative DNA damage in a group of patients with BC in relation to healthy
      controls. We also observed the difference in effectiveness of DNA damage repair.
      The results of present studies suggested the important role of BER pathway in BC
      development. (c) 2015 Wiley Periodicals, Inc.

PMID- 27870264
TI  - A hot topic: the genetics of adaptation to geothermal vents in Mimulus guttatus.
AB  - Identifying the individual loci and mutations that underlie adaptation to extreme
      environments has long been a goal of evolutionary biology. However, finding the
      genes that underlie adaptive traits is difficult for several reasons. First,
      because many traits and genes evolve simultaneously as populations diverge, it is
      difficult to disentangle adaptation from neutral demographic processes. Second,
      finding the individual loci involved in any trait is challenging given the
      respective limitations of quantitative and population genetic methods. In this
      issue of Molecular Ecology, Hendrick et al. (2016) overcome these difficulties
      and determine the genetic basis of microgeographic adaptation between geothermal
      vent and nonthermal populations of Mimulus guttatus in Yellowstone National Park.
      The authors accomplish this by combining population and quantitative genetic
      techniques, a powerful, but labour-intensive, strategy for identifying individual
      causative adaptive loci that few studies have used (Stinchcombe & Hoekstra ). In
      a previous common garden experiment (Lekberg et al. 2012), thermal M. guttatus
      populations were found to differ from their closely related nonthermal neighbours
      in various adaptive phenotypes including trichome density. Hendrick et al. (2016)
      combine quantitative trait loci (QTL) mapping, population genomic scans for
      selection and admixture mapping to identify a single genetic locus underlying
      differences in trichome density between thermal and nonthermal M. guttatus. The
      candidate gene, R2R3 MYB, is homologous to genes involved in trichome development
      across flowering plants. The major trichome QTL, Tr14, is also involved in
      trichome density differences in an independent M. guttatus population comparison
      (Holeski et al. 2010) making this an example of parallel genetic evolution.

PMID- 27870265
TI  - Antizyme inhibitor 1: a potential carcinogenic molecule.
AB  - Polyamines are multivalent and organic cations essential for cellular growth,
      proliferation, differentiation, and apoptosis. Increased levels of polyamines are
      closely associated with numerous forms of cancer. An autoregulatory circuit
      composed of ornithine decarboxylase (ODC), antizyme (AZ) and antizyme inhibitor
      (AZI) govern the intracellular level of polyamines. Antizyme binds with ODC to
      inhibit ODC activity and to promote the ubiquitin-independent degradation of ODC.
      Antizyme inhibitor binds to AZ with a higher affinity than ODC. Consequently, ODC
      is released from the ODC-AZ complex to rescue its activity. Antizyme inhibitor
      increases the ODC activity to accelerate the formation of intracellular
      polyamines, triggering gastric and breast carcinogenesis as well as
      hepatocellular carcinoma and esophageal squamous cell carcinoma development.
      Antizyme inhibitor 1 (AZIN1), a primary member of the AZI family, has aroused
      more attention because of its contribution to cancer. Even though its
      conformation is changed by adenosine-to-inosine (A->I) RNA editing, it plays an
      important role in tumorigenesis through regulating intracellular polyamines.
      Encouragingly, AZIN1 has been revealed to have an additional function outside the
      polyamine pathway so as to bypass the deficiency of targeting the polyamine
      biosynthetic pathway, promising to become a critical target for cancer therapy.
      Here, we review the latest research advances into AZIN1 and its potential
      contribution to carcinogenesis.

PMID- 27870266
TI  - Potential urinary biomarkers of nephrotoxicity in cyclophosphamide-treated rats
      investigated by NMR-based metabolic profiling.
AB  - The anticancer-drug cyclophosphamide (CP) is known to have nephrotoxicity. The
      aim of this study was to identify urinary biomarkers indicating CP-induced
      nephrotoxicity. We investigated the urine metabolic profiles using nuclear
      magnetic resonance spectrometry of rats administered with single high-doses of CP
      (0, 30, and 100 mg/kg body weight) and daily low-doses over a 4-week period (0,
      1, 3, and 10 mg/kg body weight). Among 18 identified urinary metabolites, 2
      oxoglutarate, citrate, hippurate, formate, valine, and alanine for short-term and
      2-oxoglutarate, citrate, hippurate, isoleucine, leucine, allantoin, valine, and
      lysine for long-term were selected as potential biomarkers. Pathway-enrichment
      analysis suggested that the urinary metabolism of CP is related to valine,
      leucine, and isoleucine biosynthesis; taurine and hypotaurine metabolism;
      glyoxylate and dicarboxylate metabolism; citrate cycle; and alanine, aspartate,
      and glutamate metabolism, with high pathway impact. The potential biomarkers
      obtained in this study could be used to monitor CP-induced nephrotoxicity
      relative to dose and treatment time.

PMID- 27870268
TI  - Digesting cytotoxic stressors - an unconventional mechanism to induce autophagy.
AB  - Autophagy is an essential and fundamental pathway that clears unwanted or damaged
      material from the cell. Initiation of autophagy was previously shown to be
      dependent on the Ulk1/2 kinase complex. In this issue of The FEBS Journal, Braden
      and Neufeld investigated the Ulk3 homolog in Drosophila, and proposed a novel,
      Ulk1/2 independent pathway for autophagy initiation.

PMID- 27870269
TI  - How to write a scientific paper.
AB  - In the first instalment of the Words of Advice series, we feature the essentials
      of good manuscript writing with practical tips on how to plan, organise and write
      a standout scientific paper.

PMID- 27870271
TI  - Words of Advice: for what it's worth, our tuppenceworth.
AB  - This new series in The FEBS Journal aims to provide insight and advice to
      graduate students and postdocs on topics relevant to their research and careers.

PMID- 27870267
TI  - Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult
      Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis.
AB  - In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are
      removed by apoptosis, and the adult epithelial stem (AE) cells appear
      concomitantly. They proliferate and differentiate to form the adult epithelium
      (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by
      regulating the expression of various genes including Notch receptor. To study the
      role of Notch signaling, we have analyzed the expression of its components,
      including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in
      the metamorphosing intestine by real-time reverse transcription-polymerase chain
      reaction and in situ hybridization or immunohistochemistry. We show that they are
      up-regulated during both natural and TH-induced metamorphosis in a tissue
      specific manner. Particularly, Hairy1 is specifically expressed in the AE cells.
      Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating
      tadpoles with a gamma-secretase inhibitor (GSI), which inhibits Notch signaling.
      More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell
      marker, was suppressed by GSI treatment. Our results suggest that Notch signaling
      plays a role in stem cell development by regulating the expression of Hairy genes
      during intestinal remodeling. Furthermore, we show with organ culture experiments
      that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia
      of secretory cells and reduction of absorptive cells. Our findings here thus
      provide evidence for evolutionarily conserved role of Notch signaling in
      intestinal cell fate determination but more importantly reveal, for the first
      time, an important role of Notch pathway in the formation of adult intestinal
      stem cells during vertebrate development. Stem Cells 2017;35:1028-1039.

PMID- 27870272
TI  - The airway device preference may affect the overlapping of the common carotid
      artery by the internal jugular vein.
AB  - BACKGROUND: Anatomical variation in the internal jugular vein (IJV), as well as
      its small size, tendency to collapse, and proximity to the common carotid artery
      (CCA) makes central venous cannulation via the IJV a technically challenging
      procedure, especially in pediatric patients. AIM: We evaluated the effects of
      laryngeal mask airway insertion and endotracheal intubation (ETT) on the
      anatomical relationship between the IJV and the CCA in neutral and 40 degrees 
      head away positions. METHOD: After parental consent 92 patients with ASA physical
      status I-II, aged 0-17, undergoing elective urological surgery were enrolled and
      divided into two groups according to the airway management device used for
      anesthesia: Group laryngeal mask airway (n = 63) and Group ETT (n = 29). An
      ultrasonographic evaluation was performed before and after airway instrumentation
      at neutral and 40 degrees  head rotation. The IJV position in relation to the CCA
      was noted, and the overlap percentage of the CCA was calculated as the ratio of
      the CCA length covering by the internal jugular vein to the transverse diameter
      of the CCA. RESULTS: With no airway device insertion, the position of the IJV was
      found to be anterolateral to the CCA in the majority of patients (48.8% vs 35.3%,
      right vs left IJV) in the neutral head position. While there was no significant
      change in the overlap percentages of the CCA after laryngeal mask airway
      insertion in the neutral head position [48.71% vs 57.30% for the right IJV
      (difference in median: -21.20; 95% confidence interval (CI) of difference: -56.92
      to 14.52; P = 0.133); 52.54% vs 60.36% for the left IJV (difference in median: 
      10.3; 95% CI of difference: -41.49 to 20.89; P = 0.128)], it increased
      significantly in the 40 degrees  head away position on both sides [50.11% vs
      64.83% for the right IJV (difference in median: -55; 95% CI of difference: -84 to
      -25.24; P = 0.01); 53.82% vs 71.20% for the left IJV (difference in median: -46;
      95% CI of difference: -86.85 to -5.15; P = 0.004)]. However, the overlap
      percentages of CCA decreased significantly on the right side with patients in a
      neutral head position (31.23% vs 6.27%, difference in median: 19; 95% CI of
      difference: -5.68 to 43.68; P = 0.002) and on both sides in the 40 degrees  head
      away position [29.50% vs 16.19%, difference in median: 26; 95% CI of difference:
      2.84 to 49.16; P = 0.03 and 47% vs 31.94%, difference in median: 9.50; 95% CI of
      difference: -40.87 to 59.87; P = 0.03 for the right and left sides, respectively]
      after ETT insertion. CONCLUSIONS: Laryngeal mask airway with 40 degrees  head
      rotation increases, whereas ETT decreases, the overlap percentage of CCA by IJV.
      Both head position and airway management methods have an influence on the overlap
      of the CCA by the IJV in pediatric patients.

PMID- 27870273
TI  - Response to comment "Cox: alternative therapies and postoperative vomiting".

PMID- 27870276
TI  - In this issue: December 2016.

PMID- 27870275
TI  - Comment on: S. M. Moeen 'Could acupuncture be an adequate alternative to
      dexamethasone in pediatric tonsillectomy?'

PMID- 27870277
TI  - Intravenous dexmedetomidine as an 'adjuvant' to the infant spinal anesthetic.

PMID- 27870278
TI  - Acupuncture may be an effective supplement treatment for dexamethasone in
      pediatric tonsillectomy.

PMID- 27870282
TI  - Pomolic Acid Inhibits Invasion of Breast Cancer Cells Through the Suppression of
      CXC Chemokine Receptor Type 4 Expression. Buyun Kim, Ji-Hun Kim, Byoungduck Park.

PMID- 27870283
TI  - Corrigendum: Synergistic Effects of Metals in a Promising RuII -PtII Assembly for
      a Combined Anticancer Approach: Theoretical Exploration of the Photophysical
      Properties.

PMID- 27870285
TI  - Spotlights on our sister journals: Chem. Eur. J. 47/2016.

PMID- 27870284
TI  - Corrigendum: Reversible Lysine Modification on Proteins by Using Functionalized
      Boronic Acids.

PMID- 27870286
TI  - Enhancing predictive accuracy and reproducibility in clinical evaluation
      research: Commentary on the special section of the Journal of Evaluation in
      Clinical Practice.
AB  - This paper introduces a special section of the current issue of the Journal of
      Evaluation in Clinical Practice that includes a set of 6 empirical articles
      showcasing a versatile, new machine-learning statistical method, known as optimal
      data (or discriminant) analysis (ODA), specifically designed to produce
      statistical models that maximize predictive accuracy. As this set of papers
      clearly illustrates, ODA offers numerous important advantages over traditional
      statistical methods-advantages that enhance the validity and reproducibility of
      statistical conclusions in empirical research. This issue of the journal also
      includes a review of a recently published book that provides a comprehensive
      introduction to the logic, theory, and application of ODA in empirical research.
      It is argued that researchers have much to gain by using ODA to analyze their
      data.

PMID- 27870287
TI  - Potential of tannin-rich plants, Leucaena leucocephala, Glyricidia sepium and
      Manihot esculenta, to reduce enteric methane emissions in sheep.
AB  - An in vivo trial was conducted in sheep to investigate the effect of three
      tropical tannin-rich plants (TRP) on methane emission, intake and digestibility.
      The TRP used were leaves of Glyricidia sepium, Leucaena leucocephala and Manihot
      esculenta that contained, respectively, 39, 75 and 92 g condensed tannins/kg DM.
      Methane was determined with the sulphur hexafluoride tracer technique. Eight
      rumen-cannulated sheep of two breeds (four Texel, four Blackbelly) were used in
      two 4 * 4 Latin square designs. Four experimental diets were tested. They
      consisted in a tropical natural grassland hay based on Dichanthium spp. fed alone
      (C) or in association with G. sepium (G), L. leucocephala (L) or M. esculenta (M)
      given as pellets at 44% of the daily ration. Daily organic matter intake was
      higher in TRP diets (686, 984, 1054 and 1186 g/day for C, G, L and M
      respectively; p < 0.05) while apparent organic matter total tract digestibility
      was not affected (69.9%, 62.8%, 65.3% and 64.7% for C, G, L and M respectively; p
      > 0.05). Methane emission was 47.1, 44.9, 33.3 and 33.5 g/kg digestible organic
      matter intake for C, G, L and M, respectively, and was significantly lower (p <
      0.05) for L and M than for G and C. Our results confirm the potential of some TRP
      to reduce methane production. The strong decrease in methane and the increase in
      intake with TRPs may be due to their presentation as pellets.

PMID- 27870288
TI  - Effect of dietary supplementation with clay-based binders on biochemical and
      histopathological changes in organs of turkey fed with aflatoxin-contaminated
      diets.
AB  - This study was carried out to investigate the effect of dietary supplementation
      with molecular or nano-clay binders on biochemical and histopathological
      examination of organs of turkeys fed diets contaminated with aflatoxin B1. Two
      hundred and sixteen unsexed 1-day-old British United Turkeys were randomly
      allotted to nine diets in a 3 * 3 factorial arrangement of diets supplemented
      with no toxin binder, molecular toxin binder (MTB) and nano-clay toxin binder,
      each contaminated with 0, 60 and 110 ppb aflatoxin B1 respectively. There were
      three replicates per treatment with eight turkeys per replicate. Biochemical
      analyses, organ weights and histopathological changes of some organs were
      examined at the end of the study which lasted for 84 days. Turkeys fed diets
      supplemented with molecular and nano-binders showed higher (p < 0.001) total
      serum protein, reduced (p < 0.001) serum uric acid and GGT concentration values
      when compared with those fed aflatoxin-contaminated diets supplemented with no
      binder. Turkeys fed aflatoxin-contaminated diets supplemented with no binder had
      increased (p < 0.001) AST and ALT concentration when compared with other
      treatments. The heaviest (p < 0.001) liver and intestinal weight was noticed with
      turkeys fed diets supplemented with no binder and contaminated with 110 ppb
      aflatoxin B1 . Pathologically, there was no visible morphological alteration
      noticed in all turkeys fed uncontaminated diets and nano-clay-supplemented group.
      Hepatic paleness, hepatomegaly and yellowish discolouration of the liver were
      observed with turkeys fed diets containing no binder but contaminated with 60 and
      110 ppb aflatoxin B1. Intestinal histopathological changes such as goblet cell
      hyperplasia, villous atrophy and diffuse lymphocytic enteritis were more
      prominent in turkeys fed diets containing no toxin binder and MTB. In conclusion,
      there were improved biochemical parameters and reduced deleterious effects of
      aflatoxin B1 in turkeys fed diet supplemented with clay binders. However, the
      improvement was more conspicuous in the nano-clay-supplemented group than
      molecular clay group.

PMID- 27870289
TI  - Effects of multistrain probiotics on growth performance, nutrient digestibility,
      blood profiles, faecal microbial shedding, faecal score and noxious gas emission
      in weaning pigs.
AB  - This experiment was conducted to investigate the efficacy of multistrain
      probiotics in weaning pigs. A total of 125 28-day-old weaning pigs [(Landrace *
      Yorkshire) * Duroc] with an initial average body weight (BW) of 7.26 +/- 0.76 kg
      were randomly allotted into 5 treatments, 5 replicate pens/treatment with 5
      pigs/pen for 42-day experiment. Dietary treatments were as follows: CON, basal
      diet; PC1, CON + 0.01% multistrain probiotics; PC2, CON + 0.03% multistrain
      probiotics; PC3, CON + 0.06% multistrain probiotics; PC4, CON + 0.1% multistrain
      probiotics. On day 14, pigs fed the PC4 diet had higher BW gain than pigs fed the
      CON diet. On day 42, pigs fed multistrain probiotics supplementation diets had
      higher BW gain than pigs fed the CON diet. From days 1 to 14, pigs fed the PC2,
      PC3 and PC4 diets had higher (p < 0.05) ADG than pigs fed the CON diet. From day
      15 to 42, pigs fed the multistrain probiotics supplementation diets had higher (p
      < 0.05) average daily gain (ADG) and gain: feed ratio (G:F) than pigs fed the CON
      diet. In the overall period, pigs fed the multistrain probiotics supplementation
      diets had higher (p < 0.05) ADG and pigs fed the PC2 and PC4 diets had higher (p
      < 0.05) G:F than pigs fed the CON diet. On day 42, pigs fed the PC4 diet had
      higher (p < 0.05) apparent total tract digestibility (ATTD) of dry matter (DM),
      nitrogen (N) and gross energy (GE), faecal Lactobacillus counts and lower (p <
      0.05) E. coli counts and NH3 emission than pigs fed the CON diet. Pigs fed the
      multistrain probiotics supplementation diets had lower (p < 0.05) H2 S and total
      mercaptans emissions than pigs fed the CON diet. Conclusions, dietary
      supplementation with 0.1% probiotics improved growth performance, nutrition
      digestibility and intestinal microflora balance and decreased faecal noxious gas
      emissions in weaning pigs.

PMID- 27870290
TI  - Assessment of USDA-NRCS rangeland conservation programs: recommendation for an
      evidence-based conservation platform.
AB  - The Conservation Effects Assessment Project (CEAP) was created in response to a
      request from the Office of Management and Budget that the U.S. Department of
      Agriculture, Natural Resource Conservation Service (USDA-NRCS) document the
      societal benefits anticipated to accrue from a major increase in conservation
      funding authorized by the 2002 Farm Bill. A comprehensive evaluation of the
      efficacy of rangeland conservation practices cost-shared with private landowners
      was unable to evaluate conservation benefits because outcomes were seldom
      documented. Four interrelated suppositions are presented to examine the causes
      underlying minimal documentation of conservations outcomes. These suppositions
      are (1) the benefits of conservation practices are considered a certainty so that
      documentation in not required, (2) there is minimal knowledge exchange between
      the USDA-NRCS and research organizations, (3) and a paucity of conservation
      relevant science, as well as (4) inadequate technical support for land owners
      following implementation of conservation practices. We then follow with
      recommendations to overcome potential barriers to documentation of conservation
      outcomes identified for each supposition. Collectively, this assessment indicates
      that the existing conservation practice standards are insufficient to effectively
      administer large conservation investments on rangelands and that modification of
      these standards alone will not achieve the goals explicitly stated by CEAP. We
      recommend that USDA-NRCS modify its conservation programs around a more
      comprehensive and integrative platform that is capable of implementing evidence
      based conservation. Collaborative monitoring organized around landowner-agency
      scientist partnerships would represent the focal point of a Conservation Program
      Assessment Network (CPAN). The primary network objective would be to establish
      missing information feedback loops between conservation practices and their
      agricultural and environmental outcomes to promote learning, adaptive management,
      and innovation. Network information would be archived and made available to guide
      other, related conservation programs in relevant ecoregions. Restructuring
      conservation programs as we recommend would (1) provide site specific
      information, learning, and accountability that has been requested by CEAP and (2)
      further advance balanced delivery of agricultural production and environmental
      quality goals.

PMID- 27870292
TI  - New activities of CASSS.

PMID- 27870291
TI  - Simultaneous quantitation of 14 active components in Yinchenhao decoction with an
      ultrahigh performance liquid chromatography-diode array detector: Method
      development and ingredient analysis of different commonly prepared samples.
AB  - J. Sep. Sci. 2016, 39, 4147-4157 DOI: 10.1002/jssc.201600284 Yinchenhao decoction
      (YCHD) is a famous Chinese herbal formula recorded in the Shang Han Lun which was
      prescribed by Zhongjing Zhang during 150-219 AD. A novel quantitative analysis
      method was developed, based on ultrahigh performance liquid chromatography
      coupled with a diode array detector for the simultaneous determination of 14 main
      active components in Yinchenhao decoction. Furthermore, the method has been
      applied for compositional difference analysis of the 14 components in eight
      normal extraction samples of Yinchenhao decoction, with the aid of hierarchical
      clustering analysis and similarity analysis. The present research could help
      hospital, factory and lab choose the best way to make Yinchenhao decoction with
      better efficacy.

PMID- 27870293
TI  - New developments in enhancing patient drug regimen compliance.

PMID- 27870296
TI  - Interactions between Private Health and Long-term Care Insurance and the Effects
      of the Crisis: Evidence for Spain.
AB  - This paper analyzes the reasons for the scarce development of the private long
      term care insurance market in Spain, and its relationship with health insurance.
      We are also interested in the effects the crisis has had both on the evolution of
      the demand for long-term care insurance and on the existence of regional
      disparities. We estimate bivariate probit models with endogenous variables using
      Spanish data from the Survey on Health and Retirement in Europe. Our results
      confirm that individuals wishing to purchase long-term care insurance are, in a
      sense, forced to subscribe a health insurance policy. In spite of this
      restriction in the supply of long-term care insurance contracts, we find its
      demand has grown in recent years, which we attribute to the budget cuts affecting
      the implementation of Spain's System of Autonomy and Attention to Dependent
      People. Regional differences in its implementation, as well as the varying
      effects the crisis has had across Spanish regions, lead to the existence of a
      crowding-in effect in the demand for long-term care insurance in those regions
      where co-payment is based on income and wealth, those that have a lower
      percentage of public long-term care beneficiaries, or those with a smaller share
      of cash benefits over total public benefits. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27870297
TI  - Household Financial Distress and Initial Endowments: Evidence from the 2008
      Financial Crisis.
AB  - This paper studies in utero exposure to the 2008 financial crisis. Exploiting the
      sudden and unexpected collapse of the Icelandic economy, I find that first
      trimester exposure to the crisis led to a sizable and significant reduction in
      birth weight, increased the probability of a low birth weight ( < 2500 g), and
      decreased the probability of a high birth weight ( > 4000 g). I also find
      evidence that the collapse reduced the sex ratio, indicating selection in utero
      due to maternal prenatal stress exposure. My results imply large welfare losses
      from financial distress that have hitherto been ignored - because children with
      worse health at birth can expect substantially lower lifetime earnings - and
      suggest that economic hardships may in general exacerbate income inequalities in
      the long run as low-income households are typically more exposed to financial
      distress. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27870295
TI  - Infections with multiple high-risk HPV types are associated with high-grade and
      persistent low-grade intraepithelial lesions of the cervix.
AB  - BACKGROUND: Infections with multiple human papillomavirus (HPV) types (mHPV) in
      Papanicolaou tests have been reported but the histologic correlation and clinical
      meaning remains debatable. METHODS: The authors prospectively tested 37 HPV types
      using the Linear Array HPV Genotyping Test and correlated the results to cytology
      and histology findings in 260 women evaluated from June 2009 to October 2011 and
      followed for up to 60 months. RESULTS: HPV was detected in 148 of 235 samples
      (63%) and high-risk HPV was detected in 132 samples (56%). mHPV infection was
      found to be twice as common as single HPV (sHPV) infection and was detected more
      frequently in low-grade squamous intraepithelial lesion (LSIL) (48 of 83 samples
      [58%]) and high-grade squamous intraepithelial lesion or invasive carcinoma (HSIL
      + (26 of 47 samples [55%]) compared with other categories (P<.001). Of 34
      LSIL/cervical intraepithelial neoplasia 1 (CIN1) index cases, 13 of 21 patients
      with mHPV (61.9%) persisted on CIN1, whereas no histologic abnormality was
      detected during follow-up in all 12 patients with sHPV infection (high risk or
      low risk) (P<.001). Eighteen of 20 patients with HSIL/cervical intraepithelial
      neoplasia 2 (CIN2) (90%) and high-risk mHPV persisted on HSIL+/CIN2 + whereas 6
      of 11 patients with sHPV infection did not demonstrate HSIL+/CIN2 + on follow-up
      (54.5%) (P = .066). Approximately 40% of women with HSIL were infected by high
      risk HPV types other than types 16 or 18. CONCLUSIONS: High-risk mHPV infection
      identified patients with persistent LSIL/CIN1 and may to help identify patients
      at higher risk of disease progression to HSIL+/CIN2+. Longer follow-up will
      clarify the role of mHPV testing in patient care. Cancer Cytopathol 2017;125:138
      143. (c) 2016 American Cancer Society.

PMID- 27870298
TI  - Health Effects of Short-Term Fluctuations in Macroeconomic Conditions: The Case
      of Hypertension for Older Americans.
AB  - We investigate the health effects of short-term macroeconomic fluctuations as
      described by changes in unemployment rate, house, and stock market price indexes.
      The 'Great Recession' provides the opportunity to conduct this analysis as it
      involved contemporaneous shocks to the labor, housing, and stock markets. Using
      panel data from the Health and Retirement Study over the period 2004-2010, we
      relate changes in hypertension status to changes in state-level unemployment rate
      and house prices and to changes in stock market prices. We consider hypertension,
      a disease related to stress and of high prevalence among older adults, that has
      received little attention in the literature linking macroeconomic conditions to
      individual health. Our analysis exploits self-reports of hypertension diagnosis
      as well as directly measured blood pressure readings. Using both measures, we
      find that the likelihood of developing hypertension is negatively related to
      changes in house prices. Also, decreasing house prices lower the probability of
      stopping hypertension medication treatment for individuals previously diagnosed
      with the condition. We do not observe significant associations between
      hypertension and either changes in unemployment rate or stock market prices. We
      document heterogeneity in the estimated health effects of the recession by
      gender, education, asset ownership, and work status. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27870299
TI  - Careful in the Crisis? Determinants of Older People's Informal Care Receipt in
      Crisis-Struck European Countries.
AB  - Macroeconomic downturns can have an important impact on the receipt of informal
      and formal long-term care, because recessions increase the number of unemployed
      and affect net wealth. This paper investigates how the market for informal care
      changed during and after the Great Recession in Europe, with particular focus on
      the determinants of care receipt. We use data from the Survey of Health, Ageing
      and Retirement in Europe, which includes a rich set of variables covering waves
      before and after the Great Recession. We find evidence of an increase in the
      availability of informal care after the economic downturn when controlling for
      year and country fixed effects. This trend is mainly driven by changes in care
      provision of individuals not cohabiting with the care recipient. We also find
      evidence of several determinants of informal care receipt changing during the
      crisis - such as physical needs, personal wealth, and household structures.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27870300
TI  - The Lasting Health Impact of Leaving School in a Bad Economy: Britons in the
      1970s Recession.
AB  - This paper investigates whether leaving school in a bad economy deteriorates
      health in the long run. It focuses on low-educated individuals in England and
      Wales who entered the labour market immediately after the 1973 oil crisis. Our
      identification strategy relies on the comparison of individuals who left school
      at the compulsory age, were born in the same year and had a similar quantity of
      education - but whose school-leaving behaviour in different years (hence,
      different economic conditions) was exogenously implied by compulsory schooling
      laws. We provide evidence that, unlike school-leavers who did postpone their
      entry into the labour market during the recessions of the 1980s and 1990s,
      pupils' decisions to leave school at the compulsory age immediately after the
      1973 oil crisis were not endogenous to the contemporaneous economic conditions at
      labour-market entry. We use a repeated cross section of individuals over the
      period 1983-2001 from the General Household Survey and adopt a lifecourse
      perspective, from 7 to 26 years after school-leaving. Our results show that poor
      economic conditions at labour-market entry are particularly damaging to women's
      health. For men, the health impact of poor economic conditions at labour-market
      entry is less obvious and not robust to all specifications. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27870301
TI  - Health Effects of Economic Crises.
AB  - This analysis summarizes prior research and uses national, US state and county
      level data from 1976 to 2013 to examine whether the mortality effects of economic
      crises differ in kind from those of the more typical fluctuations. The tentative
      conclusion is that economic crises affect mortality rates (and presumably other
      measures of health) in the same way as less severe downturns - leading to
      improvements in physical health. The effects of severe national recessions in the
      USA appear to have a beneficial effect on mortality that is roughly twice as
      strong as that predicted by the elevated unemployment rates alone, while the
      higher predicted rate of suicides during typical periods of economic weakness is
      approximately offset during severe recessions. No consistent pattern is obtained
      for more localized economic crises occurring at the state level - some estimates
      suggest larger protective mortality effects while others indicate offsetting
      deleterious consequences. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27870294
TI  - Advances on plant-pathogen interactions from molecular toward systems biology
      perspectives.
AB  - In the past 2 decades, progress in molecular analyses of the plant immune system
      has revealed key elements of a complex response network. Current paradigms depict
      the interaction of pathogen-secreted molecules with host target molecules leading
      to the activation of multiple plant response pathways. Further research will be
      required to fully understand how these responses are integrated in space and
      time, and exploit this knowledge in agriculture. In this review, we highlight
      systems biology as a promising approach to reveal properties of molecular plant
      pathogen interactions and predict the outcome of such interactions. We first
      illustrate a few key concepts in plant immunity with a network and systems
      biology perspective. Next, we present some basic principles of systems biology
      and show how they allow integrating multiomics data and predict cell phenotypes.
      We identify challenges for systems biology of plant-pathogen interactions,
      including the reconstruction of multiscale mechanistic models and the connection
      of host and pathogen models. Finally, we outline studies on resistance durability
      through the robustness of immune system networks, the identification of trade
      offs between immunity and growth and in silico plant-pathogen co-evolution as
      exciting perspectives in the field. We conclude that the development of
      sophisticated models of plant diseases incorporating plant, pathogen and climate
      properties represent a major challenge for agriculture in the future.

PMID- 27870302
TI  - The Effect on Mental Health of Retiring During the Economic Crisis.
AB  - This paper investigates the causal impact of retirement on late-life mental
      health, a growing concern for public health, because major depressive disorders
      are the second leading cause of disability. We shed light on the role of economic
      conditions in shaping the effect of retirement on mental health by exploiting
      time and regional variation in the severity of the economic crisis across 10
      European countries during 2004-2013. We use data from four waves of the Survey of
      Health, Ageing and Retirement in Europe and address the potential endogeneity of
      the retirement decision to mental health by applying a fixed-effects instrumental
      variables approach. The results indicate that retirement improves the mental
      health of men but not that of women. This effect is stronger for blue-collar men
      working in regions that have been severely hit by the economic crisis. These
      findings may be explained by the worsening of working conditions and the rise in
      job insecurity stemming from the economic downturn: under these circumstances,
      exit from the labour force is perceived as a relief. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27870303
TI  - Do Wealth Shocks Affect Health? New Evidence from the Housing Boom.
AB  - We exploit large exogenous changes in housing wealth to examine the impact of
      wealth gains and losses on individual health. In UK household, panel data house
      price increases, which endow owners with greater wealth, lower the likelihood of
      home owners exhibiting a range of non-chronic health conditions and improve their
      self-assessed health with no effect on their psychological health. These effects
      are not transitory and persist over a 10-year period. Using a range of fixed
      effects models, we provide robust evidence that these results are not biased by
      reverse causality or omitted factors. For owners' wealth gains affect labour
      supply and leisure choices indicating that house price increases allow
      individuals to reduce intensity of work with commensurate health benefits. (c)
      2016 The Authors. Health Economics Published by John Wiley & Sons, Ltd.

PMID- 27870304
TI  - Consequences of the Economic Crisis on Health and Health Care Systems.

PMID- 27870305
TI  - BAD TIMES, SLIMMER CHILDREN?
AB  - Although the majority of the literature has confirmed that recessions are
      beneficial for adults' health and babies' outcomes at delivery, this effect
      should not necessarily be the same for children. In this paper, we study the
      effect of business cycle conditions on infant underweight, overweight, and
      obesity. We exploit eight waves of repeated cross-sectional data (1987-2012) of
      the Spanish National Health Survey for children aged 2-15 and use the regional
      unemployment rate of the trimester of the interview as a proxy for the business
      cycle phase at the local level. We find that an increase in the unemployment rate
      is associated with lower obesity incidence, especially for children under 6 years
      old and over 12 years old. However, economic shocks also proof to have
      potentially negative consequences as they increase the prevalence of infant
      underweight for the same age groups. Moreover, we show that the possible
      mechanisms through which the cycle is impacting infant obesity is the nutritional
      composition of the children's diet, as well as, increases in the frequency of
      exercise. We provide some evidence that suggests that the impact of business
      cycle conditions on infant weight disorders have little objective health
      consequences in the short run. However, the potential long-term effects may
      become important as underweight during childhood is associated with worse
      outcomes later in life. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27870306
TI  - Health Disparities by Income in Spain Before and After the Economic Crisis.
AB  - Little is known about how health disparities by income change during times of
      economic crisis. We apply a decomposition method to unravel the contributions of
      income growth, income inequality and differential income mobility across socio
      demographic groups to changes in health disparities by income in Spain using
      longitudinal data from the Survey of Income and Living Conditions for the period
      2004-2012. We find a modest rise in health inequality by income in Spain in the 5
      years of economic growth prior to the start of the crisis in 2008, but a sharp
      fall after 2008. The drop mainly derives from the fact that loss of employment
      and earnings has disproportionately affected the incomes of the younger and
      healthier groups rather than the (mainly stable pension) incomes of the groups
      over 65 years. This suggests that unequal distribution of income protection by
      age may reduce health inequality in the short run after an economic recession.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27870308
TI  - Stand up for recalcitrance!

PMID- 27870307
TI  - Abrogation of Gap Junctional Communication in ES Cells Results in a Disruption of
      Primitive Endoderm Formation in Embryoid Bodies.
AB  - Gap junctional intercellular communication (GJIC) has been suggested to be
      involved in early embryonic development but the actual functional role remained
      elusive. Connexin (Cx) 43 and Cx45 are co-expressed in embryonic stem (ES) cells,
      form gap junctions and are considered to exhibit adhesive function and/or to
      contribute to the establishment of defined communication compartments. Here, we
      describe the generation of Cx43/Cx45-double deficient mouse ES cells to achieve
      almost complete breakdown of GJIC. Cre-loxP induced deletion of both, Cx43 and
      Cx45, results in a block of differentiation in embryoid bodies (EBs) without
      affecting pluripotency marker expression and proliferation in ES cells. We
      demonstrate that GJIC-incompetent ES cells fail to form primitive endoderm in EB
      cultures, representing the inductive key step of further differentiation events.
      Lentiviral overexpression of either Cx43 or Cx45 in Cx43/45 mutants rescued the
      observed phenotype, confirming the specificity and indicating a partially
      redundant function of both connexins. Upon differentiation GJIC-incompetent ES
      cells exhibit a strikingly altered subcellular localization pattern of the
      transcription factor NFATc3. Control EBs exhibit significantly more activated
      NFATc3 in cellular nuclei than mutant EBs suggesting that Cx-mediated
      communication is needed for synchronized NFAT activation to induce orchestrated
      primitive endoderm formation. Moreover, pharmacological inhibition of NFATc3
      activation by Cyclosporin A, a well-described inhibitor of calcineurin,
      phenocopies the loss of GJIC in control cells. Stem Cells 2017;35:859-871.

PMID- 27870310
TI  - Paradoxical increase in nasal airway resistance after topical nasal decongestion 
      does it really exist? A retro- and prospective study.
AB  - OBJECTIVE: To explore the prevalence and reproducibility of paradoxically
      increased nasal airway resistance after decongestion of the nasal mucosa as well
      as to identify patient-related factors associated with it. DESIGN: Retrospective
      analysis of all rhinomanometric measurements carried out at one ENT department in
      Sweden in the time between 1990 and 2010. In the baseline material, 207 of 4435
      patients (4.7%) showed a paradoxically increased nasal airway resistance >20%. A
      follow-up rhinomanometry was performed in patients eligible for the study.
      SETTING: Secondary care centre. PARTICIPANTS: Patients with paradoxically
      increased nasal airway resistance >20% who returned a complete questionnaire and
      had not undergone any nasal- or sinus surgery. Thirty-six patients (33-72 years)
      were eligible for the study. MAIN OUTCOME MEASURES: All patients answered a
      questionnaire and underwent rhinoscopy. Nasal airway resistance before and after
      decongestion with 0.1% xylometazoline hydrochloride was assessed by active
      anterior rhinomanometry. RESULTS: Twelve of thirty-six patients (33%) showed a
      paradoxically increased nasal airway resistance in the follow-up rhinomanometry.
      No patient-related factors were identified. CONCLUSION: The results indicate the
      existence and reproducibility of paradoxically increased nasal airway resistance.

PMID- 27870311
TI  - Does Local Ibandronate and/or Pamidronate Delivery Enhance Osseointegration? A
      Systematic Review.
AB  - PURPOSE: To our knowledge from indexed literature, the present study is the first
      one to systematically review the influence of local delivery of pamidronate (PAM)
      and/or ibandronate (IBA) on osseointegration enhancement. The aim of the present
      systematic review was to assess the efficacy of IBA and/or PAM local delivery
      (topically or coating on implants surfaces) in promoting osseointegration.
      MATERIALS AND METHODS: To address the focused question, "Does local IBA and/or
      PAM delivery enhances osseointegration?," indexed databases were searched without
      time or language restrictions up to and including May 2016 using various
      combinations of the following keywords: "pamidronate," "ibandronate,"
      "bisphosphonates," "osseointegration," and "topical administration." Letters to
      the Editor, historic reviews, commentaries, case series, and case reports were
      excluded. RESULTS: Fifteen studies were included. Fourteen studies were performed
      in animals and 2 were clinical trials. One study reported an experimental model
      and a clinical trial in the same publication. Results from 12 experimental
      studies and 2 clinical studies reported improved biomechanical properties and/or
      osseointegration around implants with PAM and/or IBA. Two experimental studies
      showed that PAM and/or IBA did not improve osseointegration. CONCLUSIONS: On
      experimental grounds, local IBA and/or PAM delivery seems to enhance
      osseointegration; however, from a clinical perspective, further randomized
      control trials are needed to assess the effectiveness of IBA and PAM in promoting
      osseointegration around dental implants.

PMID- 27870312
TI  - Mixed pollen load and late-acting self-incompatibility flexibility in
      Adenocalymma peregrinum (Miers) L.G. Lohmann (Bignonieae: Bignoniaceae).
AB  - Mixed cross and self-pollen load on the stigma (mixed pollination) of species
      with late-acting self-incompatibility system (LSI) can lead to self-fertilized
      seed production. This "cryptic self-fertility" may allow selfed seedling
      development in species otherwise largely self-sterile. Our aims were to check if
      mixed pollinations would lead to fruit set in LSI Adenocalymma peregrinum, and
      test for evidence of early-acting inbreeding depression in putative selfed seeds
      from mixed pollinations. Experimental pollinations were carried out in a natural
      population. Fruit and seed set from self-, cross and mixed pollinations were
      analysed. Further germination tests were carried out for the seeds obtained from
      treatments. Our results confirm self-incompatibility, and fruit set from cross
      pollinations was three-fold that from mixed pollinations. This low fruit set in
      mixed pollinations is most likely due to a greater number of self- than cross
      fertilized ovules, which promotes LSI action and pistil abortion. Likewise,
      higher percentage of empty seeds in surviving fruits from mixed pollinations
      compared with cross-pollinations is probably due to ovule discounting caused by
      self-fertilization. Moreover, germinability of seeds with developed embryos was
      lower in fruits from mixed than from cross-pollinations, and the non-viable seeds
      from mixed pollinations showed one-third of the mass of those from cross
      pollinations. The great number of empty seeds, lower germinability, lower mass of
      non-viable seeds, and higher variation in seed mass distribution in mixed
      pollinations, strongly suggests early-acing inbreeding depression in putative
      selfed seeds. In this sense, LSI and inbreeding depression acting together
      probably constrain self-fertilized seedling establishment in A. peregrinum.

PMID- 27870314
TI  - Genetic and environmental contributions to the inverse association between
      specific autistic traits and experience seeking in adults.

PMID- 27870313
TI  - Hypothalamic-specific proopiomelanocortin deficiency reduces alcohol drinking in
      male and female mice.
AB  - Opioid receptor antagonist naltrexone reduces alcohol consumption and relapse in
      both humans and rodents. This study investigated whether hypothalamic
      proopiomelanocortin (POMC) neurons (producing beta-endorphin and melanocortins)
      play a role in alcohol drinking behaviors. Both male and female mice with
      targeted deletion of two neuronal Pomc enhancers nPE1 and nPE2 (nPE-/-),
      resulting in hypothalamic-specific POMC deficiency, were studied in short-access
      (4-h/day) drinking-in-the-dark (DID, alcohol in one bottle, intermittent access
      (IA, 24-h cycles of alcohol access every other day, alcohol vs. water in a two
      bottle choice) and alcohol deprivation effect (ADE) models. Wild-type nPE+/+
      exposed to 1-week DID rapidly established stable alcohol drinking behavior with
      more intake in females, whereas nPE-/- mice of both sexes had less intake and
      less preference. Although nPE-/- showed less saccharin intake and preference than
      nPE+/+, there was no genotype difference in sucrose intake or preference in the
      DID paradigm. After 3-week IA, nPE+/+ gradually escalated to high alcohol intake
      and preference, with more intake in females, whereas nPE-/- showed less
      escalation. Pharmacological blockade of mu-opioid receptors with naltrexone
      reduced intake in nPE+/+ in a dose-dependent manner, but had blunted effects in
      nPE-/- of both sexes. When alcohol was presented again after 1-week abstinence
      from IA, nPE+/+ of both sexes displayed significant increases in alcohol intake
      (ADE or relapse-like drinking), with more pronounced ADE in females, whereas nPE
      /- did not show ADE in either sex. Our results suggest that neuronal POMC is
      involved in modulation of alcohol 'binge' drinking, escalation and 'relapse',
      probably via hypothalamic-mediated mechanisms, with sex differences.

PMID- 27870316
TI  - A comparative review of gerontological nursing citation data.
AB  - BACKGROUND: Gerontological nursing is a highly interdisciplinary specialty.
      English-language bibliometric research is scarce. OBJECTIVES: Study
      gerontological nursing literature to identify journals useful for nurses and
      researchers working with older adults, help librarians assist gerontological
      nursing authors to find publication outlets and make library collection
      decisions. METHODS: Using a combination of methods, the authors identified cited
      journals in the Journal of Gerontological Nursing (JGN) and Geriatric Nursing
      (GN) from 2008 to 2010 using part of the Nursing and Allied Health Resources
      (NAHRS) Section protocol. A list was generated and compared to the results of an
      earlier unpublished NAHRS study and an earlier review article. A second list was
      developed following set criteria of bibliometric indicators and journal lists.
      RESULTS: Zone 1 showed 28 journals, and Zone 2 had 1472 titles. Zone 1 journals
      were examined further based on the inclusion of certain bibliometrics and journal
      lists. DISCUSSION: Providing insight into the complementary use comparative
      review and citation mapping, this study reports an increase in gerontological
      nursing research from 2008 to 2010 across a diverse group of highly cited
      journals. CONCLUSION: A list of new journal titles is presented to aid collection
      development and suggestions of places to publish gerontological research.

PMID- 27870317
TI  - Learning to write through reading.
AB  - Narrowing the gap between what we want to achieve as writings - publishing a
      report of our project - and what we achieve as readers - finding a study to
      inform our practice - can be challenging. One solution in enabling us to achieve
      this goal is to learn from close reading the writing of others, including writing
      in development. Close reading, appraisal in its broadest term, encourages us to
      articulate what we, putting us in touch with how an author has organised
      information, selected their words and structured their arguments.

PMID- 27870318
TI  - Interactions and user-perceived helpfulness in diet information social questions
      & answers.
AB  - BACKGROUND: Online health information seeking using social questions and answers
      (Social Q&A) sites has been increasingly popular in recent years. It calls for
      better understanding of health information seeking behaviour and interactions
      between information seekers and information providers. OBJECTIVES: The study
      investigates how diet information seekers interact with information providers on
      WebMD Answers, which is a Social Q&A site devoted to health-related topics, and
      examines the factors that constitute a 'helpful' answer from an information
      seeker's perspective. METHODS: Bales' interaction process analysis was applied as
      the framework to analyse 568 diet-related Q&As from WebMD Answers to identify
      interaction patterns. RESULTS: Most diet information seekers post questions
      anonymously and without any detailed description. Individual experts or health
      organisations provide most answers. Overall, answers are positively received and
      had a high satisfaction rating. It was also found that information seeker
      perceived helpfulness does not depend on who answered the question but to how an
      information seeker posted the question. CONCLUSIONS: This study indicates that
      answers at WebMD Answers are helpful for diet information seekers. It sheds new
      light on the interactions during the Q&A process, preferred site functions and
      important factors that contribute to perceived helpful answers.

PMID- 27870319
TI  - Stem cell research: the role of information seeking and scanning.
AB  - BACKGROUND: The mass media have held an ongoing debate about stem cell research.
      However, few studies have investigated how individuals obtain information on stem
      cell research and whether this affects their knowledge and perspectives on stem
      cell research. OBJECTIVE: This study aims to investigate whether (i) cancer
      diagnosed and non-diagnosed individuals differ in terms of their acquisition of
      stem cell research information, (ii) whether this information acquisition is
      associated with stem cell research knowledge and perspectives and (iii) whether
      having had a cancer diagnosis moderates these associations. METHOD: A
      standardised, cross-sectional survey was conducted among a convenience sample of
      621 cancer-diagnosed and 1387 non-diagnosed individuals in Flanders (Belgium).
      RESULTS: The results indicate that stem cell research information acquisition
      explains a significant part of the variance of stem cell research knowledge
      (8.9%) and of the societal benefits of stem cell research (6.7%) and of embryonic
      stem cell research evaluation (3.9%) and morality (2%). These associations did
      not differ between cancer-diagnosed and non-diagnosed individuals but cancer
      diagnosed individuals did seek more stem cell research information. CONCLUSION:
      Acquiring stem cell research information, both intentionally and unintentionally,
      is positively related to stem cell research knowledge and perspectives. Future
      research should further identify ways to promote health information acquisition
      behaviour because it is associated with better knowledge and more positive
      opinion formation.

PMID- 27870321
TI  - Exploring trust in online health information: a study of user experiences of
      patients.co.uk.
AB  - This feature has been co-authored by Anna Cunningham and her supervisor Frances
      Johnson. It is based on the research Anna conducted for her dissertation, which
      she completed as part of her MA in Library and Information Management at
      Manchester Metropolitan University. The study explored how people assess the
      trustworthiness of online health information, and the participants were asked to
      talk aloud whilst viewing information on the consumer health information website
      patients.co.uk. The study confirmed that their assessment was based on the
      information usefulness and credibility as well as identifying the factors
      relating to information quality and website design that helped to form these
      judgements. A. M.

PMID- 27870322
TI  - Information Literacy Advocates: developing student skills through a peer support
      approach.
AB  - Since 2013/2014, an Information Literacy Advocates (ILA) scheme has been running
      at the University of Nottingham as an extracurricular module on the Nottingham
      Advantage Award programme. The Information Literacy Advocates scheme, which
      recruits medicine and health sciences students in their second year or above,
      aims to facilitate development of information literacy skills and confidence, as
      well as communication, organisation and teamwork, through the provision of peer
      support. Previous research indicates peer assistance effectively enhances such
      skills and is valued by fellow students who welcome the opportunity to approach
      more experienced students for help. This article, written by guest writer Ruth
      Curtis from the University of Nottingham, provides an overview of administering
      the ILA scheme and explores its impact on the Information Literacy Advocates,
      peers and librarians, and discusses future developments for taking the scheme
      forward. H. S.

PMID- 27870323
TI  - Inflammasome activators induce fibronectin expression and release in macrophages.
AB  - Extracellular fibronectin (Fn) can activate pro-inflammatory pathways and serves
      as an endogenous danger signalling molecule; thus, it has been suggested as a
      biomarker for several diseases. In the present study, we found that pathogen
      derived activators of the inflammasomes induce the expression and secretion of Fn
      in macrophages through a mechanism involving adenosine triphosphate and caspase-1
      activation. We also found that plasma Fn induces caspase-1 activation and cell
      death in macrophages, epithelial cells, and fibroblasts. Together, these results
      indicate that Fn plays a critical role in inflammasome-activated cells by
      amplifying caspase-1 activation and inducing inflammatory cell death.

PMID- 27870324
TI  - High Biofilm Conductivity Maintained Despite Anode Potential Changes in a
      Geobacter-Enriched Biofilm.
AB  - This study systematically assessed intracellular electron transfer (IET) and
      extracellular electron transfer (EET) kinetics with respect to anode potential
      (Eanode ) in a mixed-culture biofilm anode enriched with Geobacter spp. High
      biofilm conductivity (0.96-1.24 mS cm-1 ) was maintained during Eanode changes
      from -0.2 to +0.2 V versus the standard hydrogen electrode (SHE), although the
      steady-state current density significantly decreased from 2.05 to 0.35 A m-2 in a
      microbial electrochemical cell. Substantial increase of the Treponema population
      was observed in the biofilm anode at Eanode =+0.2 V, which reduced intracellular
      electron-transfer kinetics associated with the maximum specific substrate
      utilization rate by a factor of ten. This result suggests that fast EET kinetics
      can be maintained under dynamic Eanode conditions in a highly conductive biofilm
      anode as a result of shift of main EET players in the biofilm anode, although
      Eanode changes can influence IET kinetics.

PMID- 27870325
TI  - Building resilience in health care workers.

PMID- 27870326
TI  - Changing undergraduate attitudes to mental illness.

PMID- 27870327
TI  - Technology and medical education: change for the better?

PMID- 27870328
TI  - Teaching digital professionalism: a role for problem-based learning?

PMID- 27870329
TI  - Using social media to enhance health professional education.

PMID- 27870330
TI  - Maximising role-play as a learning modality.

PMID- 27870331
TI  - Developing as a clinical teacher.

PMID- 27870332
TI  - What do pregnant women think of student training?: response.

PMID- 27870333
TI  - A View from the Bridge: Health Economic Evaluation - A Value-Based Framework?

PMID- 27870334
TI  - Web Alert: Electron microscopy in environmental microbiology: An annotated
      selection of World Wide Web sites relevant to the topics in environmental
      microbiology.

PMID- 27870335
TI  - Invasive Ductal Carcinoma Displayed "Basal-Like" Feature Arising within a Breast
      Fibroadenoma.

PMID- 27870336
TI  - Choosing Bilateral Mastectomy.

PMID- 27870337
TI  - Breast Cancers Found with Digital Breast Tomosynthesis: A Comparison of Pathology
      and Histologic Grade.
AB  - To compare the pathology and histologic grading of breast cancers detected with
      digital breast tomosynthesis to those found with conventional digital
      mammography. The institutional review board approved this study. A database
      search for all breast cancers diagnosed from June 2012 through December 2013 was
      performed. Imaging records for these cancers were reviewed and patients who had
      screening mammography with tomosynthesis as their initial examination were
      selected. Five dedicated breast imaging radiologists reviewed each of these
      screening mammograms to determine whether the cancer was visible on conventional
      digital mammography or whether tomosynthesis was needed to identify the cancer. A
      cancer was considered mammographically occult if all five radiologists agreed
      that the cancer could not be seen on conventional digital mammography. The size,
      pathology and histologic grading for all diagnosed breast cancers were then
      reviewed. The Mann-Whitney U and Fisher exact tests were utilized to determine
      any association between imaging findings and cancer size, pathologic type and
      histologic grade. Sixty-five cancers in 63 patients were identified. Ten of these
      cancers were considered occult on conventional digital mammography and detected
      with the addition of tomosynthesis. These mammographically occult cancers were
      significantly associated with Nottingham grade 1 histologic pathology (p = 0.02),
      were smaller (median size: 6 mm versus 10 mm, p = 0.07) and none demonstrated
      axillary nodal metastases. Breast cancers identified through the addition of
      tomosynthesis are associated with Nottingham grade 1 histologic pathology and
      prognostically more favorable than cancers identified with conventional digital
      mammography alone.

PMID- 27870338
TI  - Understanding the Tie That Binds: Deciphering the World of the Zygoma.

PMID- 27870339
TI  - Zygomatic Arch Cortical Area and Diet in Haplorhines.
AB  - The influence that various types of ingested foods have on the form (size and
      shape) of specific features of the masticatory system is an area in which many
      questions remain unanswered. The bony zygomatic arch, the focus of this study, is
      directly linked to the masticatory system because it serves as the anchor for the
      masseter muscle, a primary muscle of chewing and source of masticatory force.
      However, the influence of diet and the forces associated with different diet
      types on the arch's internal bone architecture is not well understood. Despite
      the breadth of work centered around the craniofacial complex and biomechanics of
      mastication, there is a need for further investigations into the functional
      relationships between specific bony features that experience high strains, (e.g.,
      the zygomatic arch), and the masticatory forces generated by different diets
      (e.g., mechanically resistant versus non- mechanically resistant) across non
      human primates. A hypothesis and series of predictions assessing diet in relation
      to variability in cortical area distributions and values of section moduli
      (measures of bone strength) throughout the zygomatic arch were tested in a sample
      of haplorhine primates. Cortical area and measures of section moduli appear to
      track with the known masticatory strain distribution along the zygomatic arch.
      Pairwise comparisons between closely related taxa of different diets reveal
      significant differences in anterior cortical area and section moduli values.
      These results imply that differences in masticatory loading due to diet manifest
      in the zygomatic arch's internal bone structure. Anat Rec, 299:1789-1800, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27870341
TI  - Development, Structure, and Function of the Zygomatic Bones: What is New and Why
      Do We Care?
AB  - This issue of The Anatomical Record is the first of a two-volume set on the
      zygoma (also called the cheek bone, the zygomatic bone, the malar, or the jugal,
      the latter term being used in vertebrates other than mammals). The zygoma is an
      important component of the craniofacial skeleton, in which the zygoma is a
      connection between the midfacial and the cranial skeletons; has a functional role
      as the origin of one of the masticatory muscles, the masseter muscle, and several
      facial muscles; has been considered as an essential buttress of the facial
      skeleton for resisting masticatory forces; and has importance for determining
      phylogenetic relationships. In humans, the zygoma is also of aesthetic
      significance for facial appearance, and its restoration following trauma has
      resulted in a large clinical literature. In this first volume of this Special
      Issue, a wide ranging series of papers discuss studies related to issues of
      development, structure, and function of the zygoma and closely related parts of
      the craniofacial skeleton in mammals, and in particular primates. This
      Introductory article provides an overview in which we discuss the primary
      findings of these studies and some of their implications. The second volume,
      which will be published as the January 2017 issue of The Anatomical Record, will
      focus on variation and evolution of the zygoma throughout the vertebrates. Anat
      Rec, 299:1611-1615, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870340
TI  - Developmental and Evolutionary Significance of the Zygomatic Bone.
AB  - The zygomatic bone is derived evolutionarily from the orbital series. In most
      modern mammals the zygomatic bone forms a large part of the face and usually
      serves as a bridge that connects the facial skeleton to the neurocranium. Our aim
      is to provide information on the contribution of the zygomatic bone to variation
      in midfacial protrusion using three samples; humans, domesticated dogs, and
      monkeys. In each case, variation in midface protrusion is a heritable trait
      produced by one of three classes of transmission: localized dysmorphology
      associated with single gene dysfunction, selective breeding, or long-term
      evolution from a common ancestor. We hypothesize that the shape of the zygomatic
      bone reflects its role in stabilizing the connection between facial skeleton and
      neurocranium and consequently, changes in facial protrusion are more strongly
      reflected by the maxilla and premaxilla. Our geometric morphometric analyses
      support our hypothesis suggesting that the shape of the zygomatic bone has less
      to do with facial protrusion. By morphometrically dissecting the zygomatic bone
      we have determined a degree of modularity among parts of the midfacial skeleton
      suggesting that these components have the ability to vary independently and thus
      can evolve differentially. From these purely morphometric data, we propose that
      the neural crest cells that are fated to contribute to the zygomatic bone
      experience developmental cues that distinguish them from the maxilla and
      premaxilla. The spatiotemporal and molecular identity of the cues that impart
      zygoma progenitors with their identity remains an open question that will require
      alternative data sets. Anat Rec, 299:1616-1630, 2016. (c) 2016 The Authors The
      Anatomical Record Published by Wiley Periodicals, Inc.

PMID- 27870342
TI  - The Mobility of the Human Face: More than Just the Musculature.
AB  - The human face has the greatest mobility and facial display repertoire among all
      primates. However, the variables that account for this are not clear. Humans and
      other anthropoids have remarkably similar mimetic musculature. This suggests that
      differences among the mimetic muscles alone may not account for the increased
      mobility and facial display repertoire seen in humans. Furthermore, anthropoids
      themselves outpace prosimians in these categories: humans > other anthropoids >
      prosimians. This study was undertaken to clarify the morphological underpinnings
      of the increased mobility and display repertoire of the human face by
      investigating the SMAS (the superficial musculo-aponeurotic system), a connective
      tissue layer enclosing the mimetic musculature located between the skin and deep
      fascia/periosteum. Full-thickness samples from the face near the zygoma region
      from the anthropoids Homo sapiens (humans, N = 3), Pan troglodytes (chimpanzees,
      N = 3), Hylobates muelleri (gibbons, N = 1), and Macaca mulatta (rhesus macaque,
      N = 3) and the prosimians Tarsius bancanus (tarsiers, N = 1), and Otolemur
      crassicaudatus (galagos, N = 2) were used. All samples were processed for
      paraffin-based histology and stained sections were viewed under light microscopy
      to determine if a SMAS layer could be identified. Results indicate that a SMAS
      layer was present in all anthropoid species but neither of the prosimian species.
      This connective tissue layer may be a factor in the increased facial mobility and
      facial display repertoire present in these species. Anat Rec, 299:1779-1788,
      2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870343
TI  - The Biomechanics of Zygomatic Arch Shape.
AB  - Mammalian zygomatic arch shape is remarkably variable, ranging from nearly
      cylindrical to blade-like in cross section. Based on geometry, the arch can be
      hypothesized to be a sub-structural beam whose ability to resist deformation is
      related to cross sectional shape. We expect zygomatic arches with different cross
      sectional shapes to vary in the degree to which they resist local bending and
      torsion due to the contraction of the masseter muscle. A stiffer arch may lead to
      an increase in the relative proportion of applied muscle load being transmitted
      through the arch to other cranial regions, resulting in elevated cranial stress
      (and thus, strain). Here, we examine the mechanics of the zygomatic arch using a
      series of finite element modeling experiments in which the cross section of the
      arch of Pan troglodytes has been modified to conform to idealized shapes
      (cylindrical, elliptical, blade-like). We find that the shape of the zygomatic
      arch has local effects on stain that do not conform to beam theory. One exception
      is that possessing a blade-like arch leads to elevated strains at the postorbital
      zygomatic junction and just below the orbits. Furthermore, although modeling the
      arch as solid cortical bone did not have the effect of elevating strains in other
      parts of the face, as had been expected, it does have a small effect on stress
      associated with masseter contraction. These results are counterintuitive. Even
      though the arch has simple beam-like geometry, we fail to find a simple
      mechanical explanation for the diversity of arch shape. Anat Rec, 299:1734-1752,
      2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870345
TI  - Betwixt and Between: Intracranial Perspective on Zygomatic Arch Plasticity and
      Function in Mammals.
AB  - The zygomatic arch is morphologically complex, providing a key interface between
      the viscerocranium and neurocranium. It also serves as an attachment site for
      masticatory muscles, thereby linking it to the feeding apparatus. Though
      morphological variation related to differential loading is well known for many
      craniomandibular elements, the adaptive osteogenic response of the zygomatic arch
      remains to be investigated. Here, experimental data are presented that address
      the naturalistic influence of masticatory loading on the postweaning development
      of the zygoma and other cranial elements. Given the similarity of bone-strain
      levels among the zygoma and maxillomandibular elements, a rabbit and pig model
      were used to test the hypothesis that variation in cortical bone formation and
      biomineralization along the zygomatic arch and masticatory structures are linked
      to increased stresses. It was also hypothesized that neurocranial structures
      would be minimally affected by varying loads. Rabbits and pigs were raised for 48
      weeks and 8 weeks, respectively. In both experimental models, CT analyses
      indicated that elevated masticatory loading did not induce differences in
      cortical bone thickness of the zygomatic arch, though biomineralization was
      positively affected. Hypotheses were supported regarding bone formation for
      maxillomandibular and neurocranial elements. Varying osteogenic responses in the
      arch suggests that skeletal adaptation, and corresponding variation in
      performance, may reside differentially at one level of bony architecture. Thus,
      it is possible that phenotypic diversity in the mammalian zygoma is due more
      singularly to natural selection (vs. plasticity). These findings underscore the
      complexity of the zygomatic arch and, more generally, determinants of skull form.
      Anat Rec, 299:1646-1660, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870344
TI  - Elastic Properties of Chimpanzee Craniofacial Cortical Bone.
AB  - Relatively few assessments of cranial biomechanics formally take into account
      variation in the material properties of cranial cortical bone. Our aim was to
      characterize the elastic properties of chimpanzee craniofacial cortical bone and
      compare these to the elastic properties of dentate human craniofacial cortical
      bone. From seven cranial regions, 27 cylindrical samples were harvested from each
      of five chimpanzee crania. Assuming orthotropy, axes of maximum stiffness in the
      plane of the cortical plate were derived using modified equations of Hooke's law
      in a Mathcad program. Consistent orientations among individuals were observed in
      the zygomatic arch and alveolus. The density of cortical bone showed significant
      regional variation (P < 0.001). The elastic moduli demonstrated significant
      differences between sites, and a distinct pattern where E3  > E2  > E1 . Shear
      moduli were significantly different among regions (P < 0.001). The pattern by
      which chimpanzee cranial cortical bone varies in elastic properties resembled
      that seen in humans, perhaps suggesting that the elastic properties of
      craniofacial bone in fossil hominins can be estimated with at least some degree
      of confidence. Anat Rec, 299:1718-1733, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870346
TI  - Divided Zygomatic Bone in Primates With Implications of Skull Morphology and
      Biomechanics.
AB  - Typically the zygoma is a single bone in the facial skeleton whose shape uniquely
      copes with loads associated with mastication. Rarely but naturally, the zygoma is
      divided into two or more parts by supernumerary sutures. These extra
      intrazygomatic sutures are located at an area of critical morphological and
      biomechanical importance, yet their impacts have not been studied. In this study,
      the morphological and possible biomechanical consequences of the divided zygoma
      (DZ) were investigated in primates including rhesus macaques (Macaca mulatta),
      orangutans (Pongo abelii and P. pygmaeus), and modern humans (Homo sapiens).
      Results demonstrated that a unilateral supernumerary suture within the zygoma
      affected facial symmetry. The superior division of the divided zygoma was
      normally slender along with the adjacent frontal bone parts; while the inferior
      division of the divided zygoma was normally more robust, along with stronger
      temporal and maxillary bones. These were possible biomechanical consequences, in
      which the stresses incurred during normal masticatory activities were shunted
      from the upper face to the lower face, especially along the zygomatic arch. These
      findings revealed that the DZ condition would alter overall morphology of the
      midface of the affected side, and unfavorably affect the pattern of stress
      distribution in the loaded side of the face during mastication. The developmental
      mechanisms for the supernumerary sutures dividing the zygoma were unclear.
      Further insights into this rare condition may deepen our understanding of
      craniofacial form, adaptation, developmental plasticity, and evolution, and help
      to improve therapeutic philosophies in corrective and regenerative medicine. Anat
      Rec, 299:1801-1829, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870348
TI  - The Anatomical Record Celebrates Its Continuing Exploration of the Vertebrate
      Skull With Our First Two Part Special Issue: Understanding the Zygoma.

PMID- 27870347
TI  - Internal Bone Architecture in the Zygoma of Human and Pan.
AB  - The internal and external anatomy of the primate zygoma is central to orofacial
      function, health, and disease. The importance of variation in its gross
      morphology across extinct and extant primate forms has been established using
      finite element analysis, but its internal structure has yet to be explored. In
      this study, uCT is used to characterize trabecular bone morphometry in two
      separate regions of the zygoma of humans and Pan. Trabecular anisotropy and
      orientation are compared with strain orientations observed in trabecular regions
      of finite element models of four Pan crania. The results of this study show that
      trabecular bone morphometry, anisotropy, and orientation are highly compatible
      with strain orientation and magnitude in the finite element models. Trabecular
      bone in the zygoma is largely orthotropic (with bone orientation differing in
      three mutually orthogonal directions), with its primary orientation lying in the
      mediolateral direction. Trabecular bone in the zygomatic region appears to be
      highly influenced by the local strain environment, and thus may be closely linked
      to orofacial function. Anat Rec, 299:1704-1717, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27870349
TI  - Ontogeny of the Postorbital Region in Tarsiers and Other Primates.
AB  - Bony structure of the postorbital region is a key trait distinguishing major
      clades of primates. Strepsirrhines share a postorbital bar, and anthropoids share
      a complete postorbital septum. At issue is whether the partial postorbital septum
      of tarsiers unites living tarsiers more closely with anthropoids than with
      certain large-eyed Eocene fossils. Previously we reported incomplete postorbital
      closure in tarsiers at birth. In this article, we document comparative analyses
      of the postorbital region in a broad range of perinatal primates. Virtual
      reconstructions of microCT data were used to study three-dimensional structure of
      the perinatal cranium in these taxa. We also describe and illustrate formation of
      the tarsier partial postorbital septum through the perinatal period using a
      growth series of Tarsius syrichta. Our results support the hypothesis that
      partial postorbital septation in the tarsier is secondary to eye hypertrophy.
      Based on these observations, we propose a structural hypothesis for phylogenetic
      differences observed in the primate postorbital region. Specifically, we propose
      that key postorbital traits, including the frontal spur in strepsirrhines and the
      posterior lamina of the zygomatic in anthropoids, develop as a result of the
      spatial relationships of brain, eyes, and teeth. Haplorhines are united by
      expansion of the anterior cranial fossa and loss of the frontal spur. Anthropoids
      are further united to the exclusion of tarsiers by expansion of the temporal
      lobes and associated formation of the posterior lamina of the zygomatic.
      Mechanical forces related to these spatial relationships may be modulated by deep
      fascia of the orbit to induce formation of the postorbital septum. Anat Rec,
      299:1631-1645, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870350
TI  - The Periosteum of the Zygomatic Arch: Vascularization and Growth.
AB  - In addition to conveying the forces of attaching muscles and ligaments to the
      zygomatic and temporal bones, the arch periosteum is responsible for lateral
      apposition and medial resorption during the growth period. In this contribution,
      we describe the vasculature of the zygomatic arch in young pigs (Sus scrofa dom.)
      in order to understand the relationship of osseous and periosteal vessels to each
      other, to surrounding tissues, and to patterns of modeling. Subjects 2-6 weeks of
      age were perfused with vascular fill; some also received the vital bone label
      calcein. Whole mounts were prepared of the decalcified bony arch and of its
      lateral periosteum. Undecalcified arches were plastic-embedded and thick
      sectioned. Additional observations on cell replication were made using material
      from a previous study. The osseous and periosteal vascular supplies were largely
      independent, joined only by a fine network at the tissue interface. Osseous
      vessels entered the medial side of the arch through clusters of nutrient
      foramina. The intraosseous branching pattern resembled the direction of
      appositional growth, which in turn describes the disposition of bony trabeculae
      in older pigs. In contrast, vessels arrived at the periosteum via muscles and
      ligaments and thus its perfusion may partially depend on functional activity. The
      open weave of periosteal vessels bore little similarity to bone architecture,
      especially for the temporal bone, but the appositional lateral periosteum showed
      indications of angiogenesis, whereas the thinner, resorptive periosteum on the
      medial side featured composite, possibly fusing vessels at the bone surface. Anat
      Rec, 299:1661-1670, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870352
TI  - Membranous Support for Eyes of Strepsirrhine Primates and Fruit Bats.
AB  - Living primates have relatively large eyes and support orbital tissues with a
      postorbital bar (POB) and/or septum. Some mammals with large eyes lack a POB, and
      presumably rely on soft tissues. Here, we examined the orbits of four species of
      strepsirrhine primates (Galagidae, Cheirogaleidae) and three species of fruit
      bats (Pteropodidae). Microdissection and light microscopy were employed to
      identify support structures of the orbit. In bats and primates, there are two
      layers of fascial sheets that border the eye laterally. The outer membrane is the
      most superficial layer of deep fascia, and has connections to the POB in
      primates. In fruit bats, which lacked a POB or analogous ligament, the deep
      fascia is reinforced by transverse ligaments. Bats and primates have a deeper
      membrane supporting the eye, identified as the periorbita (PA) based on the
      presence of elastic fibers and smooth muscle. The PA merges with periostea deep
      within the orbit, but has no periosteal attachment to the POB of primates. These
      findings demonstrate that relatively big eyes can be supported primarily with
      fibrous connective tissues as well as the PA, in absence of a POB or ligament.
      The well-developed smooth muscle component within the PA of fruit bats likely
      helps to protrude the eye, maintaining a more convergent eye orientation, with
      greater overlap of the visual fields. The possibility should be considered that
      early euprimates, and even stem primates that may have lacked a POB, also had
      more convergent eyes than indicated by osseous measurements of orbital
      orientation. Anat Rec, 299:1690-1703, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870351
TI  - Review of In Vivo Bone Strain Studies and Finite Element Models of the Zygomatic
      Complex in Humans and Nonhuman Primates: Implications for Clinical Research and
      Practice.
AB  - The craniofacial skeleton is often described in the clinical literature as being
      comprised of vertical bony pillars, which transmit forces from the toothrow to
      the neurocranium as axial compressive stresses, reinforced transversely by
      buttresses. Here, we review the literature on bony microarchitecture, in vivo
      bone strain, and finite-element modeling of the facial skeleton of humans and
      nonhuman primates to address questions regarding the structural and functional
      existence of facial pillars and buttresses. Available bone material properties
      data do not support the existence of pillars and buttresses in humans or Sapajus
      apella. Deformation regimes in the zygomatic complex emphasize bending and shear,
      therefore conceptualizing the zygomatic complex of humans or nonhuman primates as
      a pillar obscures its patterns of stress, strain, and deformation. Human fossil
      relatives and chimpanzees exhibit strain regimes corroborating the existence of a
      canine-frontal pillar, but the notion of a zygomatic pillar has no support. The
      emerging consensus on patterns of strain and deformation in finite element models
      (FEMs) of the human facial skeleton corroborates hypotheses in the clinical
      literature regarding zygomatic complex function, and provide new insights into
      patterns of failure of titanium and resorbable plates in experimental studies. It
      is suggested that the "pillar and buttress" model of human craniofacial skeleton
      function be replaced with FEMs that more accurately and precisely represent in
      vivo function, and which can serve as the basis for future research into implants
      used in restoration of occlusal function and fracture repair. Anat Rec, 299:1753
      1778, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870354
TI  - Nomenclature for factors of the HLA system, update August 2016.

PMID- 27870353
TI  - Eye Size and Set in Small-Bodied Fossil Primates: A Three-Dimensional Method.
AB  - We introduce a new method to geometrically reconstruct eye volume and placement
      in small-bodied primates based on the three-dimensional contour of the
      intraorbital surface. We validate it using seven species of living primates, with
      dry skulls and wet dissections, and test its application on seven species of
      Paleogene fossils of interest. The method performs well even when the orbit is
      damaged and incomplete, lacking the postorbital bar and represented only by the
      orbital floor. Eye volume is an important quantity for anatomic and metabolic
      reasons, which due to differences in eye set, or position within (or outside) the
      bony orbit, can be underestimated in living and fossil forms when calculated from
      aperture diameter. Our Ectopic Index quantifies how much the globe's volume
      protrudes anteriorly from the aperture. Lemur, Notharctus and Rooneyia resemble
      anthropoids, with deeply recessed eyes protruding 11%-13%. Galago and Tarsius are
      the other extreme, at 47%-56%. We argue that a laterally oriented aperture has
      little to do with line-of-sight in euprimates, as large ectopic eyes can position
      the cornea to enable a directly forward viewing axis, and soft tissue positions
      the eyes facing forward in megachiropteran bats, which have unenclosed, open eye
      sockets. The size and set of virtual eyes reconstructed from 3D cranial models
      confirm that eyes were large to hypertrophic in Hemiacodon, Necrolemur,
      Microchoerus, Pseudoloris and Shoshonius, but eye size in Rooneyia may have been
      underestimated by measuring the aperture, as in Aotus. Anat Rec, 299:1671-1689,
      2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870355
TI  - Impact of genomic risk factors on survival after haematopoietic stem cell
      transplantation for patients with acute leukaemia.
AB  - The EBMT risk score is an established tool successfully used in the prognosis of
      survival post-HSCT and is applicable for a range of haematological disorders. One
      of its main advantages is that score generation involves summation of clinical
      parameters that are available pretransplant. However, the EBMT risk score is
      recognized as not being optimal. Previous analyses, involving patients with
      various diagnoses, have shown that non-HLA gene polymorphisms influence outcome
      after allogeneic HSCT. This study is novel as it focuses only on patients having
      acute leukaemia (N = 458) and attempts to demonstrate how non-HLA gene
      polymorphisms can be added to the EBMT risk score in a Cox regression model to
      improve prognostic ability for overall survival. The results of the study found
      that three genetic factors improved EBMT risk score. The presence of MAL
      (rs8177374) allele T in the patient, absence of glucocorticoid receptor haplotype
      (consisting of rs6198, rs33389 and rs33388) ACT in the patient and absence of
      heat-shock protein 70-hom (+2437) (rs2227956) allele C in the patient were
      associated with decreased survival time. When compared to the EBMT risk score,
      the scores combining EBMT risk score with the genetic factors had an improved
      correlation with clinical outcome and better separation of risk groups. A
      bootstrapping technique, involving repeated testing of a model using multiple
      validation sets, also revealed that the newly proposed model had improved
      predictive value when compared to the EBMT risk score alone. Results support the
      view that non-HLA polymorphisms could be useful for pretransplant clinical
      assessment and provide evidence that polymorphisms in the recipient genotype may
      influence incoming donor cells, suppressing the initiation of the graft versus
      leukaemia effect and reducing survival.

PMID- 27870356
TI  - Clinical and immunological relevance of antibodies in solid organ
      transplantation.
AB  - The two important issues affecting recipients of solid organ transplants and of
      importance to immunologists are (i) sensitization of the recipient to HLA
      antigens and the resultant humoral immune response leading to the development of
      anti-HLA antibodies; and ii) development of robust assays for early detection of
      humoral rejection post-transplant. Evidence from several studies clearly
      indicates that presence of circulating anti-HLA antibodies especially donor
      specific leads to early graft loss and high titres of DSA may even lead to
      hyperacute or accelerated acute rejection. Long-term graft survival too is
      adversely affected by the presence of either pre- or post-transplant DSA. HLA
      matching status of the recipient - donor pair - is an important factor in the
      modulation of humoral response following transplantation and in a way affects de
      novo development of DSA. Data collected over the past decade clearly indicate
      significantly lower level of DSAs in optimally matched donor-recipient pairs. HLA
      mismatches especially those on HLA-DR and HLA-C loci have wider implications on
      post-transplant graft survival. The presence of circulating anti-HLA antibodies
      leads to endothelial damage in the newly grafted organ through complement
      dependent or independent pathways. Although detection of C4d deposition in renal
      biopsies serves as an important indicator of humoral rejection, its absence does
      not preclude the presence of DSAs and humoral rejection, and hence, it cannot be
      relied upon in every case. The emergence of epitope-based screening for anti-HLA
      antibodies on Luminex platform with high degree of sensitivity has revolutionized
      the screening for anti-HLA antibodies and DSAs. Studies indicate that humoral
      response to non-HLA antigens might also have a detrimental effect on allograft
      survival. High titres of such circulating antibodies may even lead to hyperacute
      rejection. Pre-emptive testing of solid organ recipients, especially kidney
      transplant recipients for anti-HLA and non-HLA antibodies and aggressive post
      transplant monitoring of allograft function to detect DSAs using Luminex-based
      tests, is highly recommended.

PMID- 27870357
TI  - Nomenclature for factors of the HLA system, update September 2016.

PMID- 27870359
TI  - Open partial nephrectomy is still alive.

PMID- 27870360
TI  - Single nucleotide polymorphisms of the vascular endothelial growth factor
      receptor - a promising biomarker in metastatic renal cell carcinoma.

PMID- 27870358
TI  - Nomenclature for factors of the HLA system, update July 2016.

PMID- 27870361
TI  - What is behind the flare phenomenon?

PMID- 27870362
TI  - Light reflectance spectroscopy is one more emerging technique with the potential
      to adjust excision limits during radical prostatectomy.

PMID- 27870363
TI  - 'Killing two birds with one stone': patient-reported quality-of-life outcomes
      from the Prostate Testing for Cancer and Treatment (ProtecT) trial.

PMID- 27870364
TI  - The Prostate Testing for Cancer and Treatment (ProtecT) study: what have we
      learnt?

PMID- 27870366
TI  - Convenor's Welcome 2016.

PMID- 27870371
TI  - COSA President's Welcome.

PMID- 27870377
TI  - COSA Highlighted Lectures and Awards 2016.

PMID- 27870378
TI  - COSA-ANZBCTG Exhibitor Profiles.

PMID- 27870379
TI  - ANZBCTG Awards 2016.

PMID- 27870383
TI  - National Speakers.

PMID- 27870384
TI  - High flow nasal cannula use outside of the ICU; factors associated with failure.
AB  - OBJECTIVES: High flow nasal cannula (HFNC) use is increasing in pediatrics. Few
      studies exist examining the safety of HFNC use outside the intensive care unit
      (ICU). This study aimed to characterize patient qualities associated with failure
      of HFNC use outside the ICU. STUDY DESIGN: A retrospective chart review of
      patients placed on HFNC outside the ICU from September 2011 to July 2013 was
      completed. Failure was defined as intubation or cardiopulmonary arrest. Two
      sample tests and binary logistic regression determined significant factors
      associated with failed HFNC administration, both unadjusted and adjusted for
      hospital. RESULTS: Two hundred thirty-one patients met inclusion criteria, with
      192 receiving treatment for a primary respiratory diagnosis (83%). Fourteen (6%)
      progressed to HFNC failure; 12 transferred to the ICU and were intubated, two
      with congenital heart disease suffered cardiopulmonary arrest on the floor. Two
      sample tests revealed failure patients were more likely to have a cardiac history
      (P = 0.026), history of intubation (P = 0.040), and require higher fraction of
      inspired oxygen (FiO2 ) (median 100%; 25th-75th 60-100%; P = <0.001). Hospital
      adjusted logistic regression further demonstrated failure patients were more
      likely to be treated with higher FiO2 (OR: 38.3; 95% CI: 4.0-366.3; P = 0.002),
      and less likely to have a diagnosis of bronchiolitis (OR: 0.3; 95% CI: 0.1-0.9; P
      = 0.048). CONCLUSIONS: High FiO2 requirements, history of intubation, and cardiac
      co-morbidity are associative predictors of HFNC failure. Bronchiolitis patients
      may be treated with HFNC outside of the ICU with lower odds of failure. Pediatr
      Pulmonol. 2017;52:806-812. (c) 2017 Wiley Periodicals, Inc.

PMID- 27870386
TI  - Hyaluronic Acid Derivative with Improved Versatility for Processing and
      Biological Functionalization.

PMID- 27870387
TI  - Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and
      management.
AB  - : Disease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm
      (MPN) characterized by stem cell-derived clonal myeloproliferation that is often
      but not always accompanied by JAK2, CALR or MPL mutation, abnormal cytokine
      expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary
      hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression and
      shortened survival. DIAGNOSIS: Diagnosis is based on bone marrow morphology. The
      presence of JAK2, CALR or MPL mutation is supportive but not essential for
      diagnosis; approximately 90% of patients carry one of these mutations and 10% are
      "triple-negative." None of these mutations are specific to PMF and are also seen
      in essential thrombocythemia (ET). According to the revised 2016 World Health
      Organization (WHO) classification and diagnostic criteria, "prefibrotic" PMF (pre
      PMF) is distinguished from "overtly fibrotic" PMF; the former might mimic ET in
      its presentation and it is prognostically relevant to distinguish the two. Risk
      stratification: The Dynamic International Prognostic Scoring System-plus (DIPSS
      plus) uses eight predictors of inferior survival: age >65 years, hemoglobin <10
      g/dL, leukocytes >25 * 109 /L, circulating blasts >=1%, constitutional symptoms,
      red cell transfusion dependency, platelet count <100 * 109 /L and unfavorable
      karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, 
      7/7q-, i(17q), inv(3), 5/5q-, 12p-, or 11q23 rearrangement). The presence of 0,
      1, "2 or 3" and >=4 adverse factors defines low, intermediate-1, intermediate-2
      and high-risk disease with median survivals of approximately 15.4, 6.5, 2.9 and
      1.3 years, respectively. Most recently, DIPSS-plus-independent adverse prognostic
      relevance has been demonstrated for certain mutations including ASXL1 and SRSF2
      whereas patients with type 1/like CALR mutations, compared to their counterparts
      with other driver mutations, displayed significantly better survival. Risk
      adapted therapy: Observation alone is a reasonable treatment strategy for
      asymptomatic low or intermediate-1 DIPSS-plus risk disease, especially in the
      absence of high-risk mutations. All other patients with high or intermediate-2
      risk disease, or those harboring high-risk mutations such as ASXL1 or SRSF2,
      should be considered for stem cell transplant, which is currently the only
      treatment modality with the potential to favorably modify the natural history of
      the disease. Non-transplant candidates should be encouraged to participate in
      clinical trials, since the value of conventional drug therapy, including the use
      of JAK2 inhibitors, is limited to symptoms palliation and reduction in spleen
      size. Specifically, JAK2 inhibitors have not been shown to induce complete
      clinical or cytogenetic remissions or significantly affect JAK2/CALR/MPL mutant
      allele burden. Splenectomy is considered for drug-refractory splenomegaly.
      Involved field radiotherapy is most useful for post-splenectomy hepatomegaly, non
      hepatosplenic EMH, PMF-associated pulmonary hypertension and extremity bone pain.
      Am. J. Hematol. 91:1262-1271, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870389
TI  - Endogenous pararetroviruses in rice genomes as a fossil record useful for the
      emerging field of palaeovirology.

PMID- 27870388
TI  - Glycidol: an Hydroxyl-Containing Epoxide Playing the Double Role of Substrate and
      Catalyst for CO2 Cycloaddition Reactions.
AB  - Glycidol is converted into glycerol carbonate (GC) by coupling with CO2 in the
      presence of tetrabutylammonium bromide (TBAB) under mild reaction conditions
      (T=60  degrees C, PCO2 =1 MPa) in excellent yields (99 %) and short reaction time
      (t=3 h). The unusual reactivity of this substrate compared to other epoxides,
      such as propylene oxide, under the same reaction conditions is clearly related to
      the presence of a hydroxyl functionality on the oxirane ring. Density functional
      theory calculations (DFT) supported by 1 H NMR experiments reveal that the unique
      behavior of this substrate is a result of the formation of intermolecular
      hydrogen bonds into a dimeric structure, activating this molecule to nucleophilic
      attack, and allowing the formation of GC. Furthermore, the glycidol/TBAB
      catalytic system acts as an efficient organocatalyst for the cycloaddition of CO2
      to various oxiranes.

PMID- 27870390
TI  - Corrigendum: Hibicuslide C-induced cell death in Candida albicans involves
      apoptosis mechanism.

PMID- 27870393
TI  - Sexual modulation of sex-shared neurons and circuits in Caenorhabditis elegans.
AB  - Studies using the nematode C. elegans have provided unique insights into the
      development and function of sex differences in the nervous system. Enabled by the
      relative simplicity of this species, comprehensive studies have solved the
      complete cellular neuroanatomy of both sexes as well as the complete neural
      connectomes of the entire adult hermaphrodite and the adult male tail. This work,
      together with detailed behavioral studies, has revealed three aspects of sex
      differences in the nervous system: sex-specific neurons and circuits; circuits
      with sexually dimorphic synaptic connectivity; and sex differences in the
      physiology and functions of shared neurons and circuits. At all of these levels,
      biological sex influences neural development and function through the activity of
      a well-defined genetic hierarchy that acts throughout the body to translate
      chromosomal sex into the state of a master autosomal regulator of sexual
      differentiation, the transcription factor TRA-1A. This Review focuses on the role
      of genetic sex in implementing sex differences in shared neurons and circuits,
      with an emphasis on linking the sexual modulation of specific neural properties
      to the specification and optimization of sexually divergent and dimorphic
      behaviors. An important and unexpected finding from these studies is that
      chemosensory neurons are a primary focus of sexual modulation, with genetic sex
      adaptively shaping chemosensory repertoire to guide behavioral choice.
      Importantly, hormone-independent functions of genetic sex are the principal
      drivers of all of these sex differences, making nematodes an excellent model for
      understanding similar but poorly understood mechanisms that likely act throughout
      the animal kingdom. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870392
TI  - Brain circuitry associated with the development of substance use in bipolar
      disorder and preliminary evidence for sexual dimorphism in adolescents.
AB  - Substance use disorders and mood disorders are highly comorbid and confer a high
      risk for adverse outcomes. However, data are limited on the neurodevelopmental
      basis of this comorbidity. Substance use initiation typically occurs during
      adolescence, and sex-specific developmental mechanisms are implicated. In this
      preliminary study, we review the literature and investigate regional gray matter
      volume (GMV) associated with subsequent substance use problems in adolescents
      with bipolar disorder (BD) and explore these associations for females and males.
      Thirty adolescents with DSM-IV-diagnosed BD and minimal alcohol/substance
      exposure completed baseline structural magnetic resonance imaging scans. At
      follow-up (on average 6 years post baseline), subjects were administered the
      CRAFFT interview and categorized into those scoring at high ( >= 2: CRAFFTHIGH )
      vs. low ( < 2: CRAFFTLOW ) risk for alcohol/substance problems. Lower GMV in
      prefrontal, insular, and temporopolar cortices were observed at baseline among
      adolescents with BD reporting subsequent alcohol and cannabis use compared to
      adolescents with BD who did not (P < 0.005, clusters >= 20 voxels). Lower
      dorsolateral prefrontal GMV was associated with future substance use in both
      females and males. In females, lower orbitofrontal and insula GMV was associated
      with future substance use, while in males, lower rostral prefrontal GMV was
      associated with future use. Lower orbitofrontal, insular, and temporopolar GMV
      was observed in those who transitioned to smoking tobacco. Findings indicate that
      GMV development is associated with risk for future substance use problems in
      adolescents with BD, with results implicating GMV development in regions
      subserving emotional regulation in females and regions subserving executive
      processes and attention in males. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870394
TI  - Sex differences, gender and addiction.
AB  - This review discusses alcohol and other forms of drug addiction as both a
      sociocultural and biological phenomenon. Sex differences and gender are not
      solely determined by biology, nor are they entirely sociocultural. The
      interactions among biological, environmental, sociocultural, and developmental
      influences result in phenotypes that may be more masculine or more feminine.
      These gender-related sex differences in the brain can influence the responses to
      drugs of abuse, progressive changes in the brain after exposure to drugs of abuse
      and whether addiction results from drug-taking experiences. In addition, the
      basic laboratory evidence for sex differences is discussed within the context of
      four types of sex/gender differences. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870398
TI  - Is it time to resurrect "lazaroids"?

PMID- 27870397
TI  - Sex differences in neuroimmunity and pain.
AB  - Differences in the prevalence of chronic pain in women vs. men are well known,
      and decades of laboratory experimentation have demonstrated that women are more
      sensitive to pain than are men. Attention has thus shifted to investigating
      mechanisms underlying such differences. Recent evidence suggests that neuroimmune
      modulation of pain may represent an important cause of sex differences. The
      current Review examines the evidence for gonadal hormone modulation of the immune
      system, immune system modulation of pain, and interactions that might help to
      explain sex differences in pain. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870396
TI  - Impact of gender on corticotropin-releasing factor and noradrenergic sensitivity
      in cocaine use disorder.
AB  - Responses to stress may be important in understanding gender differences in
      substance use disorders and may also be a target for development of treatment
      interventions. A growing body of both preclinical and clinical research supports
      important underlying gender differences in the corticotropin-releasing factor
      (CRF) and noradrenergic systems, which may contribute to drug use. Preclinical
      models have demonstrated increased sensitivity of females to CRF and
      noradrenergic-induced drug reinstatement compared with males, and, consistent
      with these findings, human laboratory studies have demonstrated greater
      sensitivity to corticotropin-releasing hormone (CRH) and noradrenergic
      stimulation in cocaine-dependent women compared with men. Furthermore,
      neuroimaging studies have demonstrated increased neural response to stressful
      stimuli in cocaine-dependent women compared with men as well as showing
      significant sex differences in the sensitivity of brain regions responsible for
      regulating the response to CRH. Development of interventions targeting the
      noradrenergic system and stress response in drug-dependent individuals could have
      important clinical implications for both women and men. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870395
TI  - Sex differences in associations of arginine vasopressin and oxytocin with resting
      state functional brain connectivity.
AB  - Oxytocin (OT) and arginine vasopressin (AVP) exert robust and sexually dimorphic
      influences on cognition and emotion. How these hormones regulate relevant
      functional brain systems is not well understood. OT and AVP serum concentrations
      were assayed in 60 healthy individuals (36 women). Brain functional networks
      assessed with resting-state functional magnetic resonance imaging (rs-fMRI) were
      constructed with graph theory-based approaches that characterize brain networks
      as connected nodes. Sex differences were demonstrated in rs-fMRI. Men showed
      higher nodal degree (connectedness) and efficiency (information propagation
      capacity) in left inferior frontal gyrus (IFG) and bilateral superior temporal
      gyrus (STG) and higher nodal degree in left rolandic operculum. Women showed
      higher nodal betweenness (being part of paths between nodes) in right putamen and
      left inferior parietal gyrus (IPG). Higher hormone levels were associated with
      less intrinsic connectivity. In men, higher AVP was associated with lower nodal
      degree and efficiency in left IFG (pars orbitalis) and left STG and less
      efficiency in left IFG (pars triangularis). In women, higher AVP was associated
      with lower betweenness in left IPG, and higher OT was associated with lower nodal
      degree in left IFG (pars orbitalis). Hormones differentially correlate with brain
      networks that are important for emotion processing and cognition in men and
      women. AVP in men and OT in women may regulate orbital frontal cortex
      connectivity, which is important in emotion processing. Hormone associations with
      STG and pars triangularis in men and parietal cortex in women may account for
      well-established sex differences in verbal and visuospatial abilities,
      respectively. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870401
TI  - Sex differences in hippocampal function.
AB  - Sex differences in the function of the hippocampus have been observed in numerous
      mammalian species. However, the magnitude, extent, and specificity of these
      differences are unclear because they can depend on factors including age,
      methodology, and environment. This Review will discuss seminal studies examining
      sex differences in hippocampal memory, neuronal morphology, synaptic plasticity,
      and cell signaling in humans and rodents. We also describe possible
      organizational and activational effects of sex steroid hormones during early
      development, puberty, and adulthood that may lead to sex differences observed in
      the hippocampus. We conclude by discussing the implications of sex differences in
      hippocampal function for mental health. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870403
TI  - Sex differences in social cognition: The case of face processing.
AB  - Several studies have demonstrated that women show a greater interest for social
      information and empathic attitude than men. This article reviews studies on sex
      differences in the brain, with particular reference to how males and females
      process faces and facial expressions, social interactions, pain of others, infant
      faces, faces in things (pareidolia phenomenon), opposite-sex faces, humans vs.
      landscapes, incongruent behavior, motor actions, biological motion, erotic
      pictures, and emotional information. Sex differences in oxytocin-based attachment
      response and emotional memory are also mentioned. In addition, we investigated
      how 400 different human faces were evaluated for arousal and valence dimensions
      by a group of healthy male and female University students. Stimuli were carefully
      balanced for sensory and perceptual characteristics, age, facial expression, and
      sex. As a whole, women judged all human faces as more positive and more arousing
      than men. Furthermore, they showed a preference for the faces of children and the
      elderly in the arousal evaluation. Regardless of face aesthetics, age, or facial
      expression, women rated human faces higher than men. The preference for opposite-
      vs. same-sex faces strongly interacted with facial age. Overall, both women and
      men exhibited differences in facial processing that could be interpreted in the
      light of evolutionary psychobiology. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870399
TI  - Sex differences in hippocampal area CA3 pyramidal cells.
AB  - Numerous studies have demonstrated differences between males and females in
      hippocampal structure, function, and plasticity. There also are many studies
      about the different predisposition of a males and females for disorders where the
      hippocampus plays an important role. Many of these reports focus on area CA1, but
      other subfields are also very important, and unlikely to be the same as area CA1
      based on what is known. Here we review basic studies of male and female
      structure, function, and plasticity of area CA3 pyramidal cells of adult rats.
      The data suggest that the CA3 pyramidal cells of males and females are distinct
      in structure, function, and plasticity. These sex differences cannot be simply
      explained by the effects of circulating gonadal hormones. This view agrees with
      previous studies showing that there are substantial sex differences in the brain
      that cannot be normalized by removing the gonads and depleting peripheral gonadal
      hormones. Implications of these comparisons for understanding sex differences in
      hippocampal function and dysfunction are discussed. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27870404
TI  - Why sex hormones matter for neuroscience: A very short review on sex, sex
      hormones, and functional brain asymmetries.
AB  - Biological sex and sex hormones are known to affect functional cerebral
      asymmetries (FCAs). Men are generally more lateralized than women. The effect
      size of this sex difference is small but robust. Some of the inconsistencies in
      the literature may be explained by sex-related hormonal differences. Most studies
      focusing on neuromodulatory properties of sex hormones on FCAs have investigated
      women during the menstrual cycle. Although contradictions exist, these studies
      have typically shown that levels of estradiol and/or progesterone correlate with
      the degree of FCAs, suggesting that sex differences in FCAs partially depend on
      hormonal state and day of testing. The results indicate that FCAs are not fixed
      but are hormone dependent, and as such they can dynamically change within
      relatively short periods throughout life. Many issues raised in this Mini-Review
      refer not only to FCAs but also to other aspects of functional brain
      organization, such as functional connectivity within and between the cerebral
      hemispheres. Our understanding of sex differences in brain and behavior as well
      as their clinical relevance will improve significantly if more studies routinely
      take sex and sex hormones into account. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870400
TI  - Sex differences in the anticonvulsant activity of neurosteroids.
AB  - Epilepsy is one of the leading causes of chronic neurological morbidity
      worldwide. Acquired epilepsy may result from a number of conditions, such as
      brain injury, anoxia, tumors, stroke, neurotoxicity, and prolonged seizures. Sex
      differences have been observed in many seizure types; however, some sex-specific
      seizure disorders are much more prevalent in women. Despite some inconsistencies,
      substantial data indicates that sensitivity to seizure stimuli differs between
      the sexes. Men generally exhibit greater seizure susceptibility than women,
      whereas many women with epilepsy experience a cyclical occurrence of seizures
      that tends to center around the menstrual period, which has been termed
      catamenial epilepsy. Some epilepsy syndromes show gender differences with female
      predominance or male predominance. Steroid hormones, endogenous neurosteroids,
      and sexually dimorphic neural networks appear to play a key role in sex
      differences in seizure susceptibility. Neurosteroids, such as allopregnanolone,
      reflect sex differences in their anticonvulsant activity. This Review provides a
      brief overview of the evidence for sex differences in epilepsy and how sex
      differences influence the use of neurosteroids in epilepsy and epileptogenesis.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27870405
TI  - Sex differences in brain-derived neurotrophic factor signaling: Functions and
      implications.
AB  - Brain-derived neurotrophic factor (BDNF) regulates diverse processes such as
      neuronal survival, differentiation, and plasticity. Accumulating evidence
      suggests that molecular events that direct sexual differentiation of the brain
      interact with BDNF signaling pathways. This Mini-Review first examines potential
      hormonal and epigenetic mechanisms through which sex influences BDNF signaling.
      We then examine how sex-specific regulation of BDNF signaling supports the
      development and function of sexually dimorphic neural circuits that underlie male
      specific genital reflexes in rats and song production in birds. Finally, we
      discuss the implications of sex differences in BDNF signaling for gender-biased
      presentation of neurological and psychiatric diseases such as Alzheimer's
      disease. Although this Mini-Review focuses on BDNF, we try to convey the general
      message that sex influences brain functions in complex ways and underscore the
      requirement for and challenge of expanding research on sex differences in
      neuroscience. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870402
TI  - Genetic and epigenetic factors underlying sex differences in the regulation of
      gene expression in the brain.
AB  - There are inherent biological differences between males and females that
      contribute to sex differences in brain function and to many sex-specific
      illnesses and disorders. Traditionally, it has been thought that such differences
      are due largely to hormonal regulation; however, there are also genetic and
      epigenetic effects caused by the inheritance and unequal dosage of genes located
      on the X and Y chromosomes. Here we discuss the evidence in favor of a genetic
      and epigenetic basis for sexually dimorphic behavior, as a consequence of
      underlying differences in the regulation of genes that drive brain function. A
      better understanding of sex-specific molecular processes in the brain will
      provide further insight for the development of novel therapeutic approaches for
      the treatment of neuropsychiatric disorders characterized by sex differences. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27870406
TI  - Sex-dependent consequences of neonatal brain hypoxia-ischemia in the rat.
AB  - Neonatal hypoxia-ischemia (HI) is an important cause of neurological deficits in
      humans, and the Levine-Rice model of experimental HI in the rat mimics the human
      brain lesion and the following sensory motor deficits and cognitive disabilities.
      With the growing evidence that sex influences all levels of brain functions, this
      Mini-Review highlights studies in which sex was a controlled variable and that
      provided evidence of sexual dimorphism in behavioral outcome, extension of brain
      damage, mechanisms of lesion, and treatment efficacy in the rat neonatal HI
      model. It was shown that 1) females have greater memory deficits; 2) cell death
      is dependent mainly on caspase activation in females; 3) males are more
      susceptible to oxidative stress; and 4) treatments acting on distinct cell death
      pathways afford sex-dependent neuroprotection. These tentative conclusions, along
      with growing evidence from other fields of neurobiology, support the need for
      scientists to design their experiments considering sex as an important variable;
      otherwise, important knowledge will continue to be missed. It is conceivable that
      sex can influence the development of efficacious therapeutic tools to treat
      neonates suffering from brain HI. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870407
TI  - Evolutionary framework for identifying sex- and species-specific vulnerabilities
      in brain development and functions.
AB  - Sexual selection describes the reproductive dynamics that drive the evolution of
      many sex differences but is rarely used to guide the study of brain development
      or function. This Mini-Review describes how these dynamics can result in trait
      elaboration in one sex or the other and why these traits have a heightened
      sensitivity to stressors. The framework provides a conceptual model that will
      help to organize what we know about sex differences in brain and cognition, a
      means to focus the search for additional sex differences, and a means to predict
      brain systems that are particularly vulnerable to disruption by exposure to
      stressors. This Mini-Review briefly illustrates these points using sex
      differences in birdsong and spatial navigation to highlight the benefits and the
      nuances of using evolutionary theory to help frame neuroscience studies of sex
      differences. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870409
TI  - Cognitive, behavioral, and neural consequences of sex chromosome aneuploidy.
AB  - The X chromosome has played a critical role in the development of sexually
      selected characteristics for over 300 million years, and during that time it has
      accumulated a disproportionate number of genes concerned with mental functions.
      There are relatively specific effects of X-linked genes on social cognition,
      language, emotional regulation, visuospatial, and numerical skills. Many human X
      linked genes outside the X-Y pairing pseudoautosomal regions escape X
      inactivation. Dosage differences in the expression of such genes (which
      constitute at least 15% of the total) are likely to play an important role in
      male-female neural differentiation, and in cognitive deficits and behavioral
      characteristics, particularly in the realm of social communication, that are
      associated with sex chromosome aneuploidies. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870408
TI  - Sex-specific effects of the Huntington gene on normal neurodevelopment.
AB  - Huntington disease is a neurodegenerative disorder caused by a gene (HTT) with a
      unique feature of trinucleotide repeats ranging from 10 to 35 in healthy people;
      when expanded beyond 39 repeats, Huntington disease develops. Animal models
      demonstrate that HTT is vital to brain development; however, this has not been
      studied in humans. Moreover, evidence suggests that triplet repeat genes may have
      been vital in evolution of the human brain. Here we evaluate brain structure
      using magnetic resonance imaging and brain function using cognitive tests in a
      sample of school-aged children ages 6 to 18 years old. DNA samples were processed
      to quantify the number of CAG repeats within HTT. We find that the number of
      repeats in HTT, below disease threshold, confers advantageous changes in brain
      structure and general intelligence (IQ): the higher the number of repeats, the
      greater the change in brain structure, and the higher the IQ. The pattern of
      structural brain changes associated with HTT is strikingly different between
      males and females. HTT may confer an advantage or a disadvantage depending on the
      repeat length, playing a key role in either the evolution of a superior human
      brain or development of a uniquely human brain disease. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870411
TI  - Sex, age, and sex hormones affect recall of words in a directed forgetting
      paradigm.
AB  - During the course of serious discussion, an unexpected interruption may induce
      forgetting of the original topic of a conversation. Sex, age, and sex hormone
      levels may affect frequency and extension of forgetting. In a list-method
      directed forgetting paradigm, subjects have to learn two word lists. After
      learning list 1, subjects receive either a forget or a remember list 1 cue. When
      the participants had learned list 2 and completed a distraction task, they were
      asked to write down as many recalled items as possible, starting either with list
      1 or list 2 items. In the present study, 96 naturally cycling women, 60 oral
      contraceptive users, 56 postmenopausal women, and 41 young men were assigned to
      one of these different experimental conditions. Forget-cued young subjects recall
      fewer list 1 items (list 1 forgetting) but more list 2 items (list 2 enhancement)
      compared with remember-cued subjects. However, forget-cued postmenopausal women
      showed reduced list 1 forgetting but enhanced list 2 retention. Remember-cued
      naturally cycling women recalled more list 1 items than oral contraceptive users,
      young men, and postmenopausal women. In forget-cued follicular women, salivary
      progesterone correlated positively with recalled list 2 items. Salivary 17beta
      estradiol did not correlate with recalled list 1 or list 2 items in either
      remember- or forget-cued young women. However, salivary 17beta-estradiol
      correlated with item recall in remember-cued postmenopausal women. Our findings
      suggest that sex hormones do not globally modulate verbal memory or forgetting,
      but selectively affect cue-specific processing. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870410
TI  - Sex differences in neuroinflammation and neuroprotection in ischemic stroke.
AB  - Stroke is not only a leading cause of mortality and morbidity worldwide it also
      disproportionally affects women. There are currently over 500,000 more women
      stroke survivors in the US than men, and elderly women bear the brunt of stroke
      related disability. Stroke has dropped to the fifth leading cause of death in
      men, but remains the third in women. This review discusses sex differences in
      common stroke risk factors, the efficacy of stroke prevention therapies, acute
      treatment responses, and post-stroke recovery in clinical populations. Women have
      an increased lifetime risk of stroke compared to men, largely due to a steep
      increase in stroke incidence in older postmenopausal women, yet most basic
      science studies continue to only evaluate young male animals. Women also have an
      increased lifetime prevalence of many common stroke risk factors, including
      hypertension and atrial fibrillation, as well as abdominal obesity and metabolic
      syndrome. None of these age-related risk factors have been well modeled in the
      laboratory. Evidence from the bench has implicated genetic and epigenetic
      factors, differential activation of cell-death programs, cell-cell signaling
      pathways, and systemic immune responses as contributors to sex differences in
      ischemic stroke. The most recent basic scientific findings have been summarized
      in this review, with an emphasis on factors that differ between males and females
      that are pertinent to stroke outcomes. Identification and understanding of the
      underlying biological factors that contribute to sex differences will be critical
      to the development of translational targets to improve the treatment of women
      after stroke. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870412
TI  - Cortisol reactivity and emotional memory after psychosocial stress in oral
      contraceptive users.
AB  - Oral contraceptive (OC) users typically show a blunted or no cortisol response to
      psychosocial stress. Although most OC regimens include both an inactive (dummy)
      and active pill phase, studies have not systematically investigated cortisol
      responses during these pill phases. Further, high levels of cortisol following a
      stressor diminish retrieval of emotional material, but the effects of stress on
      memory among OC users are poorly understood. We examined the effects of a
      psychosocial stressor, the Trier Social Stress Test, vs. a control condition on
      cortisol responsivity and emotional memory retrieval in women tested either
      during their active (n = 18) or inactive pill phase (n = 21). In secondary
      analyses, we quantitatively compared OC users with normally cycling women and
      showed a significant lack of cortisol response during both active and inactive
      pill phase. Emotional recall did not differ between active and inactive pill
      phases. Stress differentially diminished recall of negative words compared with
      positive or neutral words, but cortisol levels were unrelated to memory
      performance. These findings indicate that OC users have distinct cortisol and
      memory responses to stress that are similar between the active and inactive pill
      phases. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870413
TI  - Complementarity of sex differences in brain and behavior: From laterality to
      multimodal neuroimaging.
AB  - Although, overwhelmingly, behavior is similar in males and females, and,
      correspondingly, the brains are similar, sex differences permeate both brain and
      behavioral measures, and these differences have been the focus of increasing
      scrutiny by neuroscientists. This Review describes milestones from more than 3
      decades of research in brain and behavior. This research was necessarily bound by
      available methodology, and we began with indirect behavioral indicators of brain
      function such as handedness. We proceeded to the use of neuropsychological
      batteries and then to structural and functional neuroimaging that provided the
      foundations of a cognitive neuroscience-based computerized neurocognitive
      battery. Sex differences were apparent and consistent in neurocognitive measures,
      with females performing better on memory and social cognition tasks and males on
      spatial processing and motor speed. Sex differences were also prominent in all
      major brain parameters, including higher rates of cerebral blood flow, higher
      percentage of gray matter tissue, and higher interhemispheric connectivity in
      females, compared with higher percentage of white matter and greater
      intrahemispheric connectivity as well as higher glucose metabolism in limbic
      regions in males. Many of these differences are present in childhood, but they
      become more prominent with adolescence, perhaps linked to puberty. Overall, they
      indicate complementarity between the sexes that would result in greater adaptive
      diversity. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870414
TI  - Sex differences in neural responses to subliminal sad and happy faces in healthy
      individuals: Implications for depression.
AB  - Twice as many women as men suffer from mood and anxiety disorders, yet the
      biological underpinnings of this phenomenon have been understudied and remain
      unclear. We and others have shown that the hemodynamic response to subliminally
      presented sad or happy faces during functional MRI (fMRI) is a robust biomarker
      for the attentional bias toward negative information classically observed in
      major depression. Here we used fMRI to compare the performance of healthy females
      (n = 28) and healthy males (n = 28) on a backward masking task using a fast event
      related design with gradient-recalled, echoplanar imaging with sensitivity
      encoding. The image data were compared across groups using a region-of-interest
      analysis with small-volume correction to control for multiple testing (Pcorrected
      < 0.05, cluster size >= 20 voxels). Notably, compared with males, females showed
      greater BOLD activity in the subgenual anterior cingulate cortex (sgACC) and the
      right hippocampus when viewing masked sad vs. masked happy faces. Furthermore,
      females displayed reduced BOLD activity in the right pregenual ACC and left
      amygdala when viewing masked happy vs. masked neutral faces. Given that we have
      previously reported similar findings for depressed participants compared with
      healthy controls (regardless of gender), our results raise the possibility that
      on average healthy females show subtle emotional processing biases that
      conceivably reflect a subgroup of women predisposed to depression. Nevertheless,
      we note that the differences between males and females were small and derived
      from region-of-interest rather than voxelwise analyses. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870416
TI  - Sex-specific mechanisms for responding to stress.
AB  - Posttraumatic stress disorder and major depression share stress as an etiological
      contributor and are more common in women than in men. Traditionally, preclinical
      studies investigating the neurobiological underpinnings of stress vulnerability
      have used only male rodents; however, recent studies that include females are
      finding sex-specific mechanisms for responding to stress. This Mini-Review
      examines recent literature using a framework developed by McCarthy and colleagues
      (2012; J Neurosci 32:2241-2247) that highlights different types of sex
      differences. First, we detail how learned fear responses in rats are sexually
      dimorphic. Then, we contrast this finding with fear extinction, which is similar
      in males and females at the behavioral level but at the circuitry level is
      associated with sex-specific cellular changes and, thus, exemplifies a sex
      convergence. Next, sex differences in stress hormones are detailed. Finally, the
      effects of stress on learning, attention, and arousal are used to highlight the
      concept of a sex divergence in which the behavior of males and females is similar
      at baseline but diverges following stressor exposure. We argue that appreciating
      and investigating the diversity of sex differences in stress response systems
      will improve our understanding of vulnerability and resilience to stress-related
      psychiatric disorders and likely lead to the development of novel therapeutics
      for better treatment of these disorders in both men and women. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870415
TI  - The importance of studying sex differences in disease: The example of multiple
      sclerosis.
AB  - To date, scientific research has often focused on one sex, with assumptions that
      study of the other sex would yield similar results. However, many diseases affect
      males and females differently. The sex of a patient can affect the risk for both
      disease susceptibility and progression. Such differences can be brought to the
      laboratory bench to be investigated, potentially bringing new treatments back to
      the clinic. This method of research, known as a "bedside to bench to bedside"
      approach, has been applied to studying sex differences in multiple sclerosis
      (MS). Females have greater susceptibly to MS, while males have worse disease
      progression. These two characteristics of the disease are influenced by the
      immune system and the nervous system, respectively. Thus, sex differences in each
      system must be studied. Personalized medicine has been at the forefront of
      research recently, and studying sex differences in disease fits with this
      initiative. This review will discuss the known sex differences in MS and
      highlight how investigating them can lead to new insights and potential
      treatments for both men and women. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870417
TI  - Gender differences in neural correlates of stress-induced anxiety.
AB  - Although gender differences have been identified as a crucial factor for
      understanding stress-related anxiety and associated clinical disorders, the
      neural mechanisms underlying these differences remain unclear. To explore gender
      differences in the neural correlates of stress-induced anxiety, the current study
      used functional magnetic resonance imaging to examine brain responses in 96
      healthy men and women with commensurable levels of trait anxiety as they engaged
      in a personalized guided imagery paradigm to provoke stress and neutral-relaxing
      experiences. During the task, a significant gender main effect emerged, with men
      displaying greater responses in the caudate, cingulate gyrus, midbrain, thalamus,
      and cerebellum. In contrast, women showed greater responses in the posterior
      insula, temporal gyrus, and occipital lobe. Additionally, a significant anxiety
      ratings * gender interaction from whole-brain regression analyses was observed in
      the dorsomedial prefrontal cortex, left inferior parietal lobe, left temporal
      gyrus, occipital gyrus, and cerebellum (P < 0.05, whole-brain family-wise error
      corrected), with positive associations between activity in these regions and
      stress-induced anxiety in women, but negative associations in men, indicating
      that men and women differentially use neural resources when experiencing stress
      induced anxiety. The findings suggest that in response to stress, there is a
      greater use of the medial prefrontal-parietal cortices in experiencing subjective
      anxiety in women, while decreased use of this circuit was associated with
      increased subjective anxiety states in men. The current study has implications
      for understanding gender-specific differences in stress-induced anxiety and
      vulnerability to stress-related clinical disorders, and for developing more
      effective treatment strategies tailored to each gender. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870420
TI  - Imaging sex/gender and autism in the brain: Etiological implications.
AB  - The male preponderance in autism prevalence has brought together the disparate
      topics of sex/gender and autism research. Two directions of neuroimaging studies
      on the relationships between sex/gender and autism may inform male-specific risk
      mechanisms and female-specific protective mechanisms of autism. First, we review
      how sex/gender moderates autism-related brain changes and how this informs
      general models of autism etiology. Better-powered human neuroimaging studies
      suggest that the brain characteristics of autism are qualitatively, rather than
      simply quantitatively, different between males and females. However, age and
      comorbidities might substantially moderate the pattern of differences. Second, we
      review how the relationship between autism-related brain changes (separately in
      males and females) and normative brain sex/gender differences informs specific
      etiological-developmental mechanisms. Both human and animal studies converge to
      indicate that the brain characteristics of autism are partly associated with
      normative brain sex/gender differences, suggesting convergence or overlap between
      the mechanisms leading to and modifying the development of autism and the
      mechanisms underlying sex differentiation and/or gender socialization. Future
      animal work needs to investigate sex differences in rodent mutants modeling
      autism-relevant genes and environmental exposures. Future human work needs to
      address the substantial phenotypic and etiological heterogeneity of autism and to
      focus on longitudinal neuroimaging studies (from early development) on the
      developmental trajectories of sex/gender-differential neural characteristics of
      autism. Combining animal and human work links up the causal chain from
      etiological factors, brain and physical development, to phenotypes. These
      together help delineate the different roles of sex and gender in relation to risk
      vs. protective mechanisms. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870418
TI  - Sex differences in innate immunity and its impact on opioid pharmacology.
AB  - Morphine has been and continues to be one of the most potent and widely used
      drugs for the treatment of pain. Clinical and animal models investigating sex
      differences in pain and analgesia demonstrate that morphine is a more potent
      analgesic in males than in females. In addition to binding to the neuronal MU
      opioid receptor, morphine binds to the innate immune receptor toll-like receptor
      4 (TLR4), located on glial cells. Activation of glial TLR4 initiates a
      neuroinflammatory response that directly opposes morphine analgesia. Females of
      many species have a more active immune system than males; however, few studies
      have investigated glial cells as a potential mechanism driving sexually dimorphic
      responses to morphine. This Mini-Review illustrates the involvement of glial
      cells in key processes underlying observed sex differences in morphine analgesia
      and suggests that targeting glia may improve current treatment strategies for
      pain. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870422
TI  - Magnetoencephalography study of different relationships among low- and high
      frequency-band neural activities during the induction of peaceful and fearful
      audiovisual modalities among males and females.
AB  - Our previous study estimated the bias from the match attributes of the auditory
      and visual modalities related to a peaceful mood in the male brain. However, the
      interactions among the four main frequency bands of neural activity remain
      unknown. Therefore, this study uses magnetoencephalography to explore gender
      differences in the perceptions of auditory and visual modalities related to
      peaceful and fearful moods. Instead of analyzing single frequencies, this study
      analyzes interactions between low-frequency phase and high-frequency amplitude to
      reflect neural communication. The top four values in each of the 10 brain regions
      were averaged to give a representative value for further analysis with repeated
      measures ANOVA. The results from the cross-frequency analyses suggest that delta
      theta, delta-alpha, delta-beta, and delta-gamma couplings are associated with
      interactions between emotion and modality; theta-alpha, theta-beta, and theta
      gamma couplings are associated with interactions between gender and emotion/time;
      alpha-beta and alpha-gamma couplings are associated with time; and beta-gamma
      coupling is associated with interactions between gender and modality. Although no
      obvious hemispheric lateralization of emotion in the macroscopic neural activity
      was found, these results reveal that males have stronger couplings (e.g., beta
      gamma coupling) in the visual modality related to peaceful mood, whereas females
      have stronger couplings (e.g., beta-gamma coupling) in the audiovisual modality
      related to fearful mood. Gender differences become much more apparent when
      analysis is based on cross-frequency coupling. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870421
TI  - Multimodal neuroimaging of male and female brain structure in health and disease
      across the life span.
AB  - Sex differences in brain development and aging are important to identify, as they
      may help to understand risk factors and outcomes in brain disorders that are more
      prevalent in one sex compared with the other. Brain imaging techniques have
      advanced rapidly in recent years, yielding detailed structural and functional
      maps of the living brain. Even so, studies are often limited in sample size, and
      inconsistent findings emerge, one example being varying findings regarding sex
      differences in the size of the corpus callosum. More recently, large-scale
      neuroimaging consortia such as the Enhancing Neuro Imaging Genetics through Meta
      Analysis Consortium have formed, pooling together expertise, data, and resources
      from hundreds of institutions around the world to ensure adequate power and
      reproducibility. These initiatives are helping us to better understand how brain
      structure is affected by development, disease, and potential modulators of these
      effects, including sex. This review highlights some established and disputed sex
      differences in brain structure across the life span, as well as pitfalls related
      to interpreting sex differences in health and disease. We also describe sex
      related findings from the ENIGMA consortium, and ongoing efforts to better
      understand sex differences in brain circuitry. (c) 2016 The Authors. Journal of
      Neuroscience Research Published by Wiley Periodicals, Inc.

PMID- 27870419
TI  - Sex differences in brain-derived neurotrophic factor signaling and functions.
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family
      that plays a critical role in numerous neuronal activities. Recent studies have
      indicated that some functions or action mechanisms of BDNF vary in a sex
      dependent manner. In particular, BDNF content in some brain parts and the
      tendency to develop BDNF deficiency-related diseases such as depression are
      greater in female animals. With the support of relevant studies, it has been
      suggested that sex hormones or steroids can modulate the activities of BDNF,
      which may account for its functional discrepancy in different sexes. Indeed, the
      cross-talk between BDNF and sex steroids has been detected for decades, and some
      sex steroids, such as estrogen, have a positive regulatory effect on BDNF
      expression and signaling. Thus, the sex of animal models that are used in
      studying the functions of BDNF is critical. This Mini-Review summarizes our
      current findings on the differences in expression, signaling, and functions of
      BDNF between sexes. We also discuss the potential mechanisms for mediating these
      differential responses, with a specific emphasis on sex steroids. By presenting
      and discussing these findings, we seek to encourage researchers to take sex
      influences into consideration when designing experiments, interpreting results,
      and drawing conclusions. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870423
TI  - Sex-based differences in brain alterations across chronic pain conditions.
AB  - Common brain mechanisms are thought to play a significant role across a multitude
      of chronic pain syndromes. In addition, there is strong evidence for the
      existence of sex differences in the prevalence of chronic pain and in the
      neurobiology of pain. Thus, it is important to consider sex when developing
      general principals of pain neurobiology. The goal of the current Mini-Review is
      to evaluate what is known about sex-specific brain alterations across multiple
      chronic pain populations. A total of 15 sex difference and 143 single-sex
      articles were identified from among 412 chronic pain neuroimaging articles.
      Results from sex difference studies indicate more prominent primary sensorimotor
      structural and functional alterations in female chronic pain patients compared
      with male chronic pain patients: differences in the nature and degree of insula
      alterations, with greater insula reactivity in male patients; differences in the
      degree of anterior cingulate structural alterations; and differences in emotional
      arousal reactivity. Qualitative comparisons of male-specific and female-specific
      studies appear to be consistent with the results from sex difference studies.
      Given these differences, mixed-sex studies of chronic pain risk creating biased
      data or missing important information and single-sex studies have limited
      generalizability. The advent of large-scale neuroimaging databases will likely
      aid in building a more comprehensive understanding of sex differences and
      commonalities in brain mechanisms underlying chronic pain. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870424
TI  - Sex-dependent differences in voluntary physical activity.
AB  - Numbers of overweight and obese individuals are increasing in the United States
      and globally, and, correspondingly, the associated health care costs are rising
      dramatically. More than one-third of children are currently considered obese with
      a predisposition to type 2 diabetes, and it is likely that their metabolic
      conditions will worsen with age. Physical inactivity has also risen to be the
      leading cause of many chronic, noncommunicable diseases (NCD). Children are more
      physically inactive now than they were in past decades, which may be due to
      intrinsic and extrinsic factors. In rodents, the amount of time engaged in
      spontaneous activity within the home cage is a strong predictor of later
      adiposity and weight gain. Thus, it is important to understand primary motivators
      stimulating physical activity (PA). There are normal sex differences in PA levels
      in rodents and humans. The perinatal environment can induce sex-dependent
      differences in PA disturbances. This Review considers the current evidence for
      sex differences in PA in rodents and humans. The rodent studies showing that
      early exposure to environmental chemicals can shape later adult PA responses are
      discussed. Next, whether there are different motivators stimulating exercise in
      male vs. female humans are examined. Finally, the brain regions, genes, and
      pathways that modulate PA in rodents, and possibly by translation in humans, are
      described. A better understanding of why each sex remains physically active
      through the life span could open new avenues for preventing and treating obesity
      in children and adults. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870425
TI  - Sex and the development of Alzheimer's disease.
AB  - Men and women exhibit differences in the development and progression of
      Alzheimer's disease (AD). The factors underlying the sex differences in AD are
      not well understood. This Review emphasizes the contributions of sex steroid
      hormones to the relationship between sex and AD. In women, events that decrease
      lifetime exposure to estrogens are generally associated with increased AD risk,
      whereas estrogen-based hormone therapy administered near the time of menopause
      may reduce AD risk. In men, estrogens do not exhibit age-related reduction and
      are not significantly associated with AD risk. Rather, normal age-related
      depletions of testosterone in plasma and brain predict enhanced vulnerability to
      AD. Both estrogens and androgens exert numerous protective actions in the adult
      brain that increase neural functioning and resilience as well as specifically
      attenuating multiple aspects of AD-related neuropathology. Aging diminishes the
      activational effects of sex hormones in sex-specific manners, which is
      hypothesized to contribute to the relationship between aging and AD. Sex steroid
      hormones may also drive sex differences in AD through their organizational
      effects during developmental sexual differentiation of the brain. Specifically,
      sex hormone actions during early development may confer inherent vulnerability of
      the female brain to development of AD in advanced age. The combined effects of
      organizational and activational effects of sex steroids yield distinct sex
      differences in AD pathogenesis, a significant variable that must be more
      rigorously considered in future research. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870429
TI  - An issue whose time has come.

PMID- 27870426
TI  - Sex-dependent effects of nicotine on the developing brain.
AB  - The use of tobacco products represents a major public health concern, especially
      among women. Epidemiological data have consistently demonstrated that women have
      less success quitting tobacco use and a higher risk for developing tobacco
      related diseases. The deleterious effects of nicotine are not restricted to
      adulthood, as nicotinic acetylcholine receptors regulate critical aspects of
      neural development. However, the exact mechanisms underlying the particular
      sensitivity of women to develop tobacco dependence have not been well elucidated.
      In this mini-review, we show that gonadal hormone-mediated sexual differentiation
      of the brain may be an important determinant of sex differences in the effects of
      nicotine. We highlight direct interactions between sex steroid hormones and
      ligand-gated ion channels critical for brain maturation, and discuss the extended
      and profound sexual differentiation of the brain. We emphasize that nicotine
      exposure during the perinatal and adolescent periods interferes with normal
      sexual differentiation and can induce long-lasting, sex-dependent alterations in
      neuronal structure, cognitive and executive function, learning and memory, and
      reward processing. We stress important age and sex differences in nicotine's
      effects and emphasize the importance of including these factors in preclinical
      research that models tobacco dependence. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870430
TI  - Sex-related influences in migraine.
AB  - Migraine is a common neurological disorder with significantly higher incidence
      and prevalence in women than men. The presentation of the disease in women is
      modulated by changes in sex hormones from adolescence to pregnancy and menopause.
      Yet, the effect of sex influences has often been neglected in both basic and
      clinical and in clinical management of the disease. In this review, evidence from
      epidemiological, clinical, animal, and neuroimaging studies on the significance
      of the sex-related influences in migraine is presented, and the unmet needs in
      each area are discussed. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870431
TI  - Sex differences in stress effects on emotional learning.
AB  - Stress influences emotional learning and memory processes. These effects are
      thought to underlie stress-associated mental disorders. Sex differences in stress
      reactivity and in central nervous system stress sensitivity illustrate the
      important modulatory role of sex hormones. This Review outlines how stress
      hormones influence different stages of the fear conditioning process, such as
      fear acquisition, extinction, and retrieval. Results will be compared with
      findings on the impact of stress on episodic memory. The focus is on the
      available human data on sex differences and the impact sex hormones have on the
      stress effects on emotional learning and memory. It will become apparent that the
      menstrual cycle but also the intake of hormonal contraceptives modulates the
      impact of stress on brain and behavior. Additional basic research is needed for a
      deeper insight regarding the interplay between stress and sex hormones in emotion
      and cognition. In addition, new treatment options might be derived to optimize
      existing strategies such as exposure therapy, which relies on the principles of
      fear conditioning. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870433
TI  - Sex differences in nonhuman primate behavioral development.
AB  - Sex differences in behavior and developmental trajectories in human children are
      of great interest to researchers in a variety of fields, and a persistent topic
      of discussion and debate is the relative contribution of biological vs. social
      influences to such differences. Given the potentially large effects of cultural
      and social influences on human child development, nonhuman primates are important
      model species for investigating the biological and evolutionary roots of sex
      differences in human development. This Mini-Review briefly summarizes the
      existing literature on sex-biased behavior toward infant nonhuman primates by
      mothers and other social partners, followed by a review of findings on sex
      differences (or lack thereof) in primate behavioral development from a variety of
      species in wild and naturalistic settings. These include differences in physical
      and social development, including play, grooming, and object manipulation
      patterns, as well as nursing and the development of foraging behavior. The Mini
      Review concludes by providing potential avenues for future research. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27870432
TI  - Sex and stress: Men and women show different cortisol responses to psychological
      stress induced by the Trier social stress test and the Iowa singing social stress
      test.
AB  - Acute psychological stress affects each of us in our daily lives and is
      increasingly a topic of discussion for its role in mental illness, aging,
      cognition, and overall health. A better understanding of how such stress affects
      the body and mind could contribute to the development of more effective clinical
      interventions and prevention practices. Over the past 3 decades, the Trier Social
      Stress Test (TSST) has been widely used to induce acute stress in a laboratory
      setting based on the principles of social evaluative threat, namely, a judged
      speech-making task. A comparable alternative task may expand options for
      examining acute stress in a controlled laboratory setting. This study uses a
      within-subjects design to examine healthy adult participants' (n = 20 men, n = 20
      women) subjective stress and salivary cortisol responses to the standard TSST
      (involving public speaking and math) and the newly created Iowa Singing Social
      Stress Test (I-SSST). The I-SSST is similar to the TSST but with a new twist:
      public singing. Results indicated that men and women reported similarly high
      levels of subjective stress in response to both tasks. However, men and women
      demonstrated different cortisol responses; men showed a robust response to both
      tasks, and women displayed a lesser response. These findings are in line with
      previous literature and further underscore the importance of examining possible
      sex differences throughout various phases of research, including design,
      analysis, and interpretation of results. Furthermore, this nascent examination of
      the I-SSST suggests a possible alternative for inducing stress in the laboratory.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27870427
TI  - Understanding the broad influence of sex hormones and sex differences in the
      brain.
AB  - Sex hormones act throughout the entire brain of both males and females via both
      genomic and nongenomic receptors. Sex hormones can act through many cellular and
      molecular processes that alter structure and function of neural systems and
      influence behavior as well as providing neuroprotection. Within neurons, sex
      hormone receptors are found in nuclei and are also located near membranes, where
      they are associated with presynaptic terminals, mitochondria, spine apparatus,
      and postsynaptic densities. Sex hormone receptors also are found in glial cells.
      Hormonal regulation of a variety of signaling pathways as well as direct and
      indirect effects on gene expression induce spine synapses, up- or downregulate
      and alter the distribution of neurotransmitter receptors, and regulate
      neuropeptide expression and cholinergic and GABAergic activity as well as calcium
      sequestration and oxidative stress. Many neural and behavioral functions are
      affected, including mood, cognitive function, blood pressure regulation, motor
      coordination, pain, and opioid sensitivity. Subtle sex differences exist for many
      of these functions that are developmentally programmed by hormones and by not yet
      precisely defined genetic factors, including the mitochondrial genome. These sex
      differences and responses to sex hormones in brain regions, which influence
      functions not previously regarded as subject to such differences, indicate that
      we are entering a new era of our ability to understand and appreciate the
      diversity of gender-related behaviors and brain functions. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870434
TI  - Do sex differences in rumination explain sex differences in depression?
AB  - It is generally accepted that women tend to ruminate more than men do and these
      thought patterns are often associated with depressive symptoms (Nolen-Hoeksema et
      al., ). Based on these findings, we considered whether the relationship between
      rumination and depression is stronger in women than in men and if so, whether
      this might explain the higher prevalence of major depressive disorder (MDD) in
      women and finally, whether the association can be disrupted through a mind/body
      intervention. Adult men and women, most of whom were clinically depressed,
      participated in an intervention known as MAP Training, which combines "mental"
      training with silent meditation and "physical" training with aerobic exercise
      (Shors et al., ). After eight weeks of training, both men and women reported
      significantly fewer symptoms of depression and fewer ruminative thoughts
      (Alderman et al., ). Statistical correlations between depressive symptoms and
      ruminative thoughts were strong and significant (rho > 0.50; p < 0.05) for both
      men and women before and after MAP Training. However, only in women did
      depressive symptoms relate to "reflective" ruminations, which involve analyses of
      past events, feelings, and behaviors. This is also the only relationship that
      dissipated after the intervention. In general, these analyses suggest that the
      strength of the relationship between depressive symptoms and rumination does not
      necessarily explain sex differences in depression; but because the relationship
      is strong, targeting rumination through intervention can reduce the incidence of
      MDD, which is more prevalent among women. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870428
TI  - (Putative) sex differences in neuroimmune modulation of memory.
AB  - The neuroimmune system is significantly sexually dimorphic, with sex differences
      evident in the number and activation states of microglia, in the activation of
      astrocytes, and in cytokine release and function. Neuroimmune cells and signaling
      are now recognized as critical for many neural functions throughout the life
      span, including synaptic plasticity and memory function. Here we address the
      question of how cytokines, astrocytes, and microglia contribute to memory, and
      specifically how neuroimmune modulation of memory differentially affects males
      and females. Understanding sex differences in both normal memory processes and
      dysregulation of memory in psychiatric and neurological disorders is critical for
      developing treatment and preventive strategies for memory disorders that are
      effective for both men and women. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870435
TI  - A general theory of sexual differentiation.
AB  - A general theory of mammalian sexual differentiation is proposed. All biological
      sex differences are the result of the inequality in effects of the sex
      chromosomes, which are the only factors that differ in XX vs. XY zygotes. This
      inequality leads to male-specific effects of the Y chromosome, including
      expression of the testis-determining gene Sry that causes differentiation of
      testes. Thus, Sry sets up lifelong sex differences in effects of gonadal
      hormones. Y genes also act outside of the gonads to cause male-specific effects.
      Differences in the number of X chromosomes between XX and XY cells cause sex
      differences in expression (1) of Xist, (2) of X genes that escape inactivation,
      and (3) of parentally imprinted X genes. Sex differences in phenotype are
      ultimately the result of multiple, independent sex-biasing factors, hormonal and
      sex chromosomal. These factors act in parallel and in combination to induce sex
      differences. They also can offset each other to reduce sex differences. Other
      mechanisms, operating at the level of populations, cause groups of males to
      differ on average from groups of females. The theory frames questions for further
      study, and directs attention to inherent sex-biasing factors that operate in many
      tissues to cause sex differences, and to cause sex-biased protection from
      disease. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870438
TI  - Sex differences in the human visual system.
AB  - This Mini-Review summarizes a wide range of sex differences in the human visual
      system, with a primary focus on sex differences in visual perception and its
      neural basis. We highlight sex differences in both basic and high-level visual
      processing, with evidence from behavioral, neurophysiological, and neuroimaging
      studies. We argue that sex differences in human visual processing, no matter how
      small or subtle, support the view that females and males truly see the world
      differently. We acknowledge some of the controversy regarding sex differences in
      human vision and propose that such controversy should be interpreted as a source
      of motivation for continued efforts to assess the validity and reliability of
      published sex differences and for continued research on sex differences in human
      vision and the nervous system in general. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870436
TI  - Stress, sex, and motivated behaviors.
AB  - Stress is a major risk factor for development of psychiatric disorders such as
      depression and development of substance use disorder. Although there are
      important sex differences in the prevalence of these disorders, most preclinical
      models used to study stress-induced disorders have used males only. Social defeat
      stress is a commonly used method to induce stress in an ethologically relevant
      way but has only recently begun to be used in female rodents. Using these new
      female models, recent studies have examined how social defeat stress affects
      males and females differently at the behavioral, circuit, and molecular levels.
      This Mini-Review discusses sex differences in the effects of social defeat stress
      on social behavior and drug-seeking behavior as well as its impact on the
      mesolimbic dopamine system and the highly connected region of the bed nucleus of
      the stria terminalis. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870439
TI  - Estradiol shifts interactions between the infralimbic cortex and central amygdala
      to enhance fear extinction memory in female rats.
AB  - There is growing evidence that estradiol (E2) enhances fear extinction memory
      consolidation. However, it is unclear how E2 influences the nodes of the fear
      extinction network to enhance extinction memory. This study begins to delineate
      the neural circuits underlying the influence of E2 on fear extinction acquisition
      and consolidation in female rats. After fear conditioning (day 1), naturally
      cycling female rats underwent extinction learning (day 2) in a low-E2 state,
      receiving a systemic administration of either E2 or vehicle prior to extinction
      training. Extinction memory recall was then tested 24 hr later (day 3). We
      measured immediate early gene c-fos expression within the extinction network
      during fear extinction learning and extinction recall. During extinction
      learning, E2 treatment increased centrolateral amygdala c-fos activity and
      reduced lateral amygdala activity relative to vehicle. During extinction recall,
      E2-treated rats exhibited reduced c-fos expression in the centromedial amygdala.
      There were no group differences in c-fos expression within the medial prefrontal
      cortex or dorsal hippocampus. Examining c-fos ratios with the infralimbic cortex
      (IL) revealed that, despite the lack of group differences within the IL, E2
      treatment induced greater IL activity relative to both prelimbic cortex and
      central amygdala (CeA) activity during extinction memory recall. Only the
      relationship between IL and CeA activity positively correlated with extinction
      retention. In conclusion, E2 appears to modify interactions between the IL and
      the CeA in females, shifting from stronger amygdalar modulation of fear during
      extinction learning to stronger IL control during extinction recall. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27870441
TI  - Sexual divergence in activity-dependent neuroprotective protein impacting autism,
      schizophrenia, and Alzheimer's disease.
AB  - Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP)
      interacts with key regulatory proteins, including the chromatin remodeling
      complex SWI/SNF, proteins associated with RNA splicing, RNA translation,
      microtubule dynamics, and autophagy. ADNP regulates > 400 genes during mouse
      embryonic development and is essential for neural tube closure. ADNP key
      functions extend from mice to men, with mutations causing ADNP-related ID/autism
      syndrome, also known as the Helsmoortel-Van der Aa syndrome. ADNP mRNA increases
      in lymphocytes derived from schizophrenia patients and in patients suffering from
      mild cognitive impairment (MCI) and further increases in Alzheimer's disease
      patients compared with controls. Serum ADNP levels correlate with IQ. NAP
      (davunetide), an ADNP snippet drug candidate, protects cognition in patients
      suffering from amnestic MCI preceding Alzheimer's disease and significantly
      enhances functional daily activities in schizophrenia patients toward future
      development. It is important to note that ADNP is sexually regulated in the
      brains of birds, mice, and men and in lymphocytes of patients suffering from
      schizophrenia. ADNP haploinsufficiency in mice results in significantly decreased
      axonal transport (with male-female differences) changes in gene expression in a
      sex-dependent manner, including key regulatory mechanisms during brain and heart
      development and function and behavioral outcomes. These findings pave the path
      for better understanding of brain function through the prism of sex differences.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27870437
TI  - Sex differences in stroke therapies.
AB  - Stroke is the fifth leading cause of death and acquired disability in aged
      populations. Women are disproportionally affected by stroke, having a higher
      incidence and worse outcomes than men. Numerous preclinical studies have
      discovered novel therapies for the treatment of stroke, but almost all of these
      have been shown to be unsuccessful in clinical trials. Despite known sex
      differences in occurrence and severity of stroke, few preclinical or clinical
      therapeutics take into account possible sex differences in treatment. Reanalysis
      of data from studies of tissue plasminogen activator (tPA), the only currently
      FDA-approved stroke therapy, has shown that tPA improves stroke outcomes for both
      sexes and also shows sexual dimorphism by more robust improvement in stroke
      outcome in females. Experimental evidence supports the inclusion of sex as a
      variable in the study of a number of novel stroke drugs and therapies, including
      preclinical studies of anti-inflammatory drugs (minocycline), stimulators of cell
      survival (insulin-like growth factor-1), and inhibitors of cell death pathways
      (pharmacological inhibition of poly[ADP-ribose] polymerase-1, nitric oxide
      production, and caspase activation) as well as in current clinical trials of stem
      cell therapy and cortical stimulation. Overall, study design and analysis in
      clinical trials as well as in preclinical studies must include both sexes
      equally, consider possible sex differences in the analyses, and report the
      differences/similarities in more systematic/structured ways to allow promising
      therapies for both sexes and increase stroke recovery. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870442
TI  - Contributory role of sex differences in the variations of gustatory function.
AB  - Remarkable variability between males and females occurs for an array of taste
      guided behaviors in both rodents and humans. Sex differences have been noted for
      taste preference, detection thresholds, and reactivity to taste stimuli.
      Manipulating sex hormones during early postnatal development or altering the
      amount of circulating estrogen in adulthood can dramatically alter the pattern of
      these behaviors. Receptors for sex hormones appear to be prominent in several
      nuclei associated with central gustatory pathways, indicating that steroid
      hormones may modulate central taste processing. Electrophysiological recordings
      from the rat brainstem suggest that taste-elicited activity to sweet stimuli is
      organized by hormones during early development, and activity during bitter
      stimulation is altered by circulating ovarian hormones. Sex differences in
      gustatory function appear to emerge at the level of the taste bud. Among
      ovariectomized rats, estradiol treatment decreases activity in the chorda tympani
      nerve during NaCl stimulation. Although there is no evidence that chorda tympani
      responses to NaCl differ between intact male and female rats, glossopharyngeal
      nerve responses are lower in intact females for both NaCl and sodium acetate.
      Responses in the glossopharyngeal nerve to citric acid stimulation are also
      higher in female rats relative to males. These findings suggest that, in addition
      to differential central modulation of taste input based on sex, taste information
      from the periphery varies between males and females. Although the extent of sex
      differences in taste processing and the underlying causal mechanisms require
      further clarification, it is clear that studying one sex alone provides an
      incomplete picture of gustatory function. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870445
TI  - Evaluating social defeat as a model for psychopathology in adult female rodents.
AB  - Social conflict is a predominant stressor in humans and is associated with
      increased risk for developing psychological illnesses including depression and
      anxiety. Overwhelmingly, more women suffer from these disorders, which may be due
      to increased stress sensitivity. Like humans, rodents experience a myriad of
      physiological and behavioral sequelae due to prolonged stress exposure. Although
      the motivation for social conflict may differ between humans and rodents, female
      rodents may provide an opportunity to explore the underlying mechanisms by which
      stress confers risk for psychopathology in women. Because most female rodents do
      not express spontaneous aggression, the majority of basic research examines the
      physiological and behavioral outcomes of social conflict in male rodents.
      However, there are instances where female rodents exhibit territorial (California
      mice and Syrian hamsters) and maternal aggression (rats, mice, and hamsters)
      creating a venue to examine sex differences in physiology and behavior in
      response to stress. While many studies rely upon nonsocial behavioral assays
      (e.g., elevated plus maze, forced swim test) to assess the impact of stress on
      emotionality, here we primarily focus on behavioral outcomes in social-based
      assays in rodents. This is critically important given that disruptions in social
      relationships can be a cause and consequence of neuropsychiatric diseases. Next,
      we briefly discuss how sex differences in the recruitment of neural circuitry
      and/or neurochemistry in response to stress may underlie sex differences in
      neuroendocrine and behavioral stress responses. Finally, the translational value
      of females in rodent stress models and considerations regarding behavioral
      interpretations of these models are discussed. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870444
TI  - Sex differences and estrogen regulation of BDNF gene expression, but not
      propeptide content, in the developing hippocampus.
AB  - Sex differences in adult brain function are frequently determined developmentally
      through the actions of steroid hormones during sensitive periods of prenatal and
      early postnatal life. In rodents, various cellular end points of the developing
      brain are affected by estradiol that is derived from the aromatization of
      circulating testosterone and/or synthesized within the brain. We have previously
      described a sex difference in neurogenesis in the hippocampus of neonatal rats
      that is modulated by estradiol. In this report, we examined a potential
      downstream regulator of the effects of estradiol on hippocampal cell
      proliferation by measuring gene expression of brain-derived neurotrophin (BDNF)
      in male and female neonatal rats in response to estradiol. Males had higher
      baseline BDNF gene expression in dentate gyrus and CA1 regions of the hippocampus
      compared with females. Neonatal administration of exogenous estradiol resulted in
      opposite effects on BDNF expression in these areas of the neonatal hippocampus,
      such that BDNF transcripts increased in CA1 but decreased in dentate. Blocking
      endogenous estradiol signaling by antagonizing estrogen receptors decreased BDNF
      expression in the dentate of males, but not females, and had no effect in CA1.
      Interestingly, this sex difference and response to estradiol was not mirrored by
      translational output, as no differences in BDNF precursor peptide were observed.
      The sex- and region-specific effects of estradiol on BDNF expression in the
      neonatal hippocampus suggest a complex functional relationship between these
      pleiotropic factors in regulating developmental neurogenesis. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27870446
TI  - Sex/gender influences on the nervous system: Basic steps toward clinical
      progress.
AB  - A Commentary highlighting the progress that sex-based data and research have made
      in neuroscience and the complexities that research has revealed thus far. Basic
      and preclinical neuroscientific research that considers sex as a biological
      variable will continue to build on the foundation of knowledge that has been
      started by multiple predecessors. The expansion of knowledge in preclinical
      neuroscience that integrates the study of both sexes will have a significant role
      in informing clinical trial design. We applaud the efforts of the editors and
      authors who have contributed to this issue. Published 2016. This article is a
      U.S. Government work and is in the public domain in the USA.

PMID- 27870447
TI  - Sex on the brain: Are gender-dependent structural and functional differences
      associated with behavior?
AB  - A substantial number of studies provide evidence documenting a variety of sex
      differences in the brain. It remains unclear whether sexual differentiation at
      the neural level is related to that observed in daily behavior, cognitive
      function, and the risk of developing certain psychiatric and neurological
      disorders. Some investigators have questioned whether the brain is truly sexually
      differentiated and support this view with several arguments including the
      following: (1) brain structural or functional differences are not necessarily
      reflected in appropriate differences at the behavioral level, which might suggest
      that these two phenomena are not linked to each other; and (2) sex-related
      differences in the brain are rather small and concern features that significantly
      overlap between males and females. This review polemicizes with those opinions
      and presents examples of sex-related local neural differences underpinning a
      variety of sex differences in behaviors, skills, and cognitive/emotional
      abilities. Although male/female brain differentiation may vary in pattern and
      scale, nonetheless, in some respects (e.g., relative local gray matter volumes)
      it can be substantial, taking the form of sexual dimorphism and involving large
      areas of the brain (the cortex in particular). A significant part of this review
      is devoted to arguing that some sex differences in the brain may serve to prevent
      (in the case where they are maladaptive), rather than to produce, differences at
      the behavioral/skill level. Specifically, some differences might result from
      compensatory mechanisms aimed at maintaining similar intellectual capacities
      across the sexes, despite the smaller average volume of the brain in females
      compared with males. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870443
TI  - Sex differences in depression during pregnancy and the postpartum period.
AB  - Women have a lifetime risk of major depression double that of men but only during
      their reproductive years. This sex difference has been attributed partially to
      activational effects of female sex steroids and also to the burdens of pregnancy,
      childbirth, and parenting. Men, in contrast, have a reproductive period difficult
      to delineate, and research on the mental health of men has rarely considered the
      effects of fatherhood. However, the couple goes through a number of potentially
      stressing events during the reproductive period, and both mothers and fathers are
      at risk of developing peripartum depression. This Review discusses the literature
      on maternal and paternal depression and the endocrine changes that may predispose
      a person to depression at this stage of life, with specific focus on the
      hypothalamus-pituitary axis, oxytocin, and testosterone levels in men. Important
      findings on sex differences in the neural correlates of maternal and paternal
      behavior have emerged, highlighting the relevance of the emotional brain in
      mothers and the sociocognitive brain in fathers and pointing toward the presence
      of a common parents' brain. Additionally, sex differences in neurogenesis and
      brain plasticity are described in relation to peripartum depression. (c) 2016 The
      Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.

PMID- 27870440
TI  - Sex differences modulating serotonergic polymorphisms implicated in the
      mechanistic pathways of risk for depression and related disorders.
AB  - Despite consistent observations of sex differences in depression and related
      emotional disorders, we do not yet know how these sex differences modulate the
      effects of genetic polymorphisms implicated in risk for these disorders. This
      Mini-Review focuses on genetic polymorphisms of the serotonergic system to
      illustrate how sex differences might modulate the neurobiological pathways
      involved in the development of depression. We consider the interacting role of
      environmental factors such as early-life stress. Given limited current knowledge
      about this topic, we highlight methodological considerations, challenges, and
      guidelines for future research. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870450
TI  - The immune system as a novel regulator of sex differences in brain and behavioral
      development.
AB  - Sexual differentiation of the brain occurs early in life as a result of sex
      typical hormone action and sex chromosome effects. Immunocompetent cells are
      being recognized as underappreciated regulators of sex differences in brain and
      behavioral development, including microglia, astrocytes, and possibly other less
      well studied cell types, including T cells and mast cells. Immunocompetent cells
      in the brain are responsive to steroid hormones, but their role in sex-specific
      brain development is an emerging field of interest. This Review presents a
      summary of what is currently known about sex differences in the number,
      morphology, and signaling profile of immune cells in the developing brain and
      their role in the early-life programming of sex differences in brain and
      behavior. We review what is currently known about sex differences in the response
      to early-life perturbations, including stress, inflammation, diet, and
      environmental pollutants. We also discuss how and why understanding sex
      differences in the developing neuroimmune environment may provide insight into
      understanding the etiology of several neurodevelopmental disorders. This Review
      also highlights what remains to be discovered in this emerging field of
      developmental neuroimmunology and underscores the importance of filling in these
      knowledge gaps. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870451
TI  - Preclinical sex differences in depression and antidepressant response:
      Implications for clinical research.
AB  - Women suffer from depression and anxiety disorders more often than men, and as a
      result they receive antidepressants to a greater extent. Sex differences in
      antidepressant response in humans have been modestly studied, and results have
      been controversial. At the same time, preclinical studies on animal models of
      depression and antidepressant response have provided insights with regard to sex
      differences that could be useful for the design and interpretation of future
      clinical trials. This Mini-Review discusses such sex-differentiated findings with
      regard to the presentation of depression, endophenotypes, and antidepressant
      response. In particular, men and women differ in symptomatology of depression,
      and animal models of depression have revealed sex differences in behavioral
      indices. However, although in experimental studies behavioral indices and models
      are adjusted to identify sex differences properly, this is not the case in the
      use of depression rating scales in clinical studies. Accordingly, preclinical
      studies highlight the importance of sex differences at the baseline behavioral
      response and the underlying mechanisms that often converge after antidepressant
      treatment. This is also a neglected issue in human studies. Finally, preclinical
      research suggests that, in the quest for potential biomarkers for depression, sex
      should be an important factor to consider. Careful consideration of sex
      differences in preclinical research could facilitate and ameliorate the design
      and quality of clinical studies for disease biomarkers and novel fast-acting
      antidepressants that are so essential for both men and women suffering from
      depression. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870449
TI  - Do cortical plasticity mechanisms differ between males and females?
AB  - The difference between male and female behavior and male and female
      susceptibility to a number of neuropsychiatric conditions is not controversial.
      From a biological perspective, one might expect to see at least some of these
      differences underpinned by identifiable physical differences in the brain. This
      Mini-Review focuses on evidence that plasticity mechanisms differ between males
      and females and ask at what scale of organization the differences might exist, at
      the systems level, the circuits level, or the synaptic level. Emerging evidence
      suggests that plasticity differences may extend to the scale of synaptic
      mechanisms. In particular, the CaMKK, NOS1 and estrogen receptor pathways show
      sexual dimorphisms with implications for plasticity in the hippocampus and
      cerebral cortex. (c) 2016 The Authors. Journal of Neuroscience Research Published
      by Wiley Periodicals, Inc.

PMID- 27870448
TI  - Sex differences in animal models of decision making.
AB  - The ability to weigh the costs and benefits of various options to make an
      adaptive decision is critical to an organism's survival and wellbeing. Many
      psychiatric diseases are characterized by maladaptive decision making, indicating
      a need for better understanding of the mechanisms underlying this process and the
      ways in which it is altered under pathological conditions. Great strides have
      been made in uncovering these mechanisms, but the majority of what is known comes
      from studies conducted solely in male subjects. In recent years, decision-making
      research has begun to include female subjects to determine whether sex
      differences exist and to identify the mechanisms that contribute to such
      differences. This Mini-Review begins by describing studies that have examined sex
      differences in animal (largely rodent) models of decision making. Possible
      explanations, both theoretical and biological, for such differences in decision
      making are then considered. The Mini-Review concludes with a discussion of the
      implications of sex differences in decision making for understanding psychiatric
      conditions. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870452
TI  - Sex, hormones, and genotype interact to influence psychiatric disease, treatment,
      and behavioral research.
AB  - Sex differences exist in the vulnerability, incidence, manifestation, and
      treatment of numerous neurological and psychiatric diseases. Despite this
      observation prominent in the literature, little consideration has been given to
      possible sex differences in outcome in both preclinical and clinical research.
      This Mini-Review highlights evidence supporting why studying sex differences
      matter for advances in brain health as well as improving treatment for
      neurological and psychiatric disease. Additionally, we discuss some statistical
      and methodological considerations in evaluating sex differences as well as how
      differences in the physiology of the sexes can contribute to sex difference in
      disease incidence and manifestation. Furthermore, we review literature
      demonstrating that the reproductive experience in the female can render the
      female brain differentially vulnerable to disease across age. Finally, we discuss
      how genes interact with sex to influence disease risk and treatment and argue
      that sex must be considered in precision medicine. Together the evidence reviewed
      here supports the inclusion of males and females at all levels of neuroscience
      research. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870453
TI  - Do microglia play a role in sex differences in TBI?
AB  - Traumatic brain injury (TBI) is one of the leading causes of morbidity and
      mortality for both males and females and is, thus, a major focus of current
      study. Although the overall death rate of TBI for males is roughly three times
      higher than that for females, males have been disproportionately represented in
      clinical and preclinical studies. Gender differences are known to exist in many
      neurologic disorders, such as multiple sclerosis and stroke, and differences
      appear to exist in TBI. Furthermore, it is known that microglia have sexually
      dimorphic roles in CNS development and other neurologic conditions; however, most
      animal studies of microglia and TBI have focused on male subjects. Microglia are
      a current target of many preclinical and clinical therapeutic trials for TBI.
      Understanding the relationship among sex, sex hormones, and microglia is critical
      to truly understanding the pathophysiology of TBI. However, the evidence for sex
      differences in TBI centers mainly on sex hormones, and evidenced-based
      conclusions are often contradictory. In an attempt to review the current
      literature, it is apparent that sex differences likely exist, but the
      contradictory nature and magnitude of such differences in the existing literature
      does not allow definite conclusions to be drawn, except that more investigation
      of this issue is necessary. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870454
TI  - Sex differences in the adolescent brain and body: Findings from the saguenay
      youth study.
AB  - This Mini-Review describes sex differences in 66 quantitative characteristics of
      the brain and body measured in a community-based sample of 1,024 adolescents 12
      18 years of age, members of the Saguenay Youth Study. Using an extensive
      phenotyping protocol, we have obtained measures in a number of domains, including
      brain structure, cognition, mental health, substance use, body composition,
      metabolism, cardiovascular reactivity, and life style. For each measure, we
      provide estimates of effect size (Cohen's d) and sex-specific correlations with
      age (Pearson R). In total 59 of the 66 characteristics showed sex differences (at
      a nominal P < 0.05), with small (32), medium-sized (13), and large (11) effects.
      Some, but not all, of these sex differences increase during adolescence; this
      appears to be the case mostly for anatomical and physiological measures. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27870455
TI  - Addressing sex as a biological variable.

PMID- 27870457
TI  - Single-nucleotide polymorphism rs948854 in human galanin gene and multiple
      sclerosis: a gender-specific risk factor.
AB  - We performed comparative analyses of the genotype distribution and allelic
      frequencies of the rs948854 polymorphism (G/A) in the galanin gene's promoter in
      patients with multiple sclerosis (MS) and in healthy matched controls. In total
      111 patients and 115 control subjects were included. The analyses revealed that
      the presence of the minor allele (G) increased susceptibility to MS in men (OR =
      2.49, P = 0.008) but not in women. The presence of the G allele in men was also
      significantly associated with the late onset of MS. Furthermore, rs948854
      polymorphism affected the rate of MS progression depending on the sex of the
      patients. In woman (typically slowly progressing), the percentage of patients
      with the slow (<0.5 EDSS score per year) progression rate was significantly
      reduced (chi2  = 5.7, P = 0.017) in the minor allele carriers group (52.6%), in
      comparison with the wild-type carriers (83.9%). In men (typically quickly
      progressing), the number of patients with fast progression rate (>=0.75 EDSS
      score per year) tended to increase in the minor allele carriers group (50%)
      compared with number of patients with the wild-type carriers (31.3%). These data
      demonstrate for the first time an association between rs948854 polymorphism and
      multiple sclerosis and, further, that this association is sex specific. They also
      point to diagnostic and prognostic benefits of genetic screening of patients with
      multiple sclerosis. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870458
TI  - In the trenches with the corpus callosum: Some redux of redux.

PMID- 27870459
TI  - Sex differences in nicotine preference.
AB  - Smoking is the major cause of preventable deaths worldwide, and although there is
      a decline in overall smoking prevalence in developed countries, the decline in
      women is less pronounced than in men. Women become dependent faster and
      experience greater difficulties in quitting. Similar trends have been observed in
      animal models of nicotine/tobacco addiction. Individual differences in
      vulnerability to drug abuse are also observed in nicotine/tobacco addiction and
      point to the importance of sex differences. This Review, summarizes findings from
      three experimental approaches used to depict nicotine preference in animal
      models, intravenous and oral nicotine self-administration and nicotine-induced
      conditioned place preference. Nicotine preference is considered to be reflected
      in the animal's motivation to administer the drug (intravenously or orally) or to
      prefer an environment paired with the presence of the drug (conditioned place
      preference). These approaches all point to the importance of sex and age of the
      subjects; the preference of females and adolescents appear to be more pronounced
      than that of males and adults, respectively. A closer look at these factors will
      help us understand the mechanisms that underlie nicotine addiction and develop
      strategies to cope. Ignoring sex differences and reaching conclusions based only
      on studies using male subjects has resulted in erroneous generalizations in the
      past. Sex differences in nicotine preference have been clearly documented, and
      awareness on this aspect of nicotine dependence will significantly impact our
      success in translational research. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870456
TI  - Understanding the epigenetic basis of sex differences in depression.
AB  - Epigenetics refers to potentially heritable processes that can mediate both
      lasting and transient changes in gene expression in the absence of genome
      sequence alterations. The field of epigenetics has introduced a novel
      understanding of the mechanisms through which the environment can shape an
      individual and potentially its offspring. This Mini-Review examines the current
      literature exploring the role of epigenetics in the development of mood disorders
      such as depression. Depression is twofold more common in females, yet the
      majority of preclinical research has been conducted exclusively in male subjects.
      Here we discuss what is known about sex differences in epigenetic regulation and
      function and how this may contribute to the etiology and onset of mood disorders.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27870460
TI  - Sex differences in the immune response to experimental stroke: Implications for
      translational research.
AB  - Ischemic stroke is a leading cause of death and disability in the United States.
      It is known that males and females respond differently to stroke. Depending on
      age, the incidence, prevalence, mortality rate, and disability outcome of stroke
      differ between the sexes. Females generally have strokes at older ages than males
      and, therefore, have a worse stroke outcome. There are also major differences in
      how the sexes respond to stroke at the cellular level. Immune response is a
      critical factor in determining the progress of neurodegeneration after stroke and
      is fundamentally different for males and females. Additionally, females respond
      to stroke therapies differently from males, yet they are often left out of the
      basic research that is focused on developing those therapies. With a resounding
      failure to translate stroke therapies from the bench to the bedside, it is
      clearer than ever that inclusion of both sexes in stroke studies is essential for
      future clinical success. This Mini-Review examines sex differences in the immune
      response to experimental stroke and its implications for therapy development. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27870463
TI  - 13 C MR Hyperpolarization of Lactate by Using ParaHydrogen and Metabolic
      Transformation in Vitro.
AB  - Hyperpolarization of the 13 C magnetic resonance signal of l-[1-13 C]lactate has
      been obtained using the chemically based, cost-effective method called
      parahydrogen-induced polarization by means of side-arm hydrogenation (PHIP-SAH).
      Two ester derivatives of lactate were tested and the factors that determine the
      polarization level on the product have been investigated in detail. The metabolic
      conversion of hyperpolarized l-[1-13 C]lactate into pyruvate has been observed in
      vitro using lactate dehydrogenase (LDH) and in a cells lysate. From the
      acquisition of a series of 13 C NMR spectra, the metabolic build-up of the [1-13
      C]pyruvate signal has been observed. These studies demonstrate that, even if the
      experimental set-up used for these PHIP-SAH hyperpolarization studies is still
      far from optimal, the attained polarization level is already sufficient to carry
      out in vitro metabolic studies.

PMID- 27870462
TI  - Sex differences in the functional lateralization of emotion and decision making
      in the human brain.
AB  - Dating back to the case of Phineas Gage, decades of neuropsychological research
      have shown that the ventromedial prefrontal cortex (vmPFC) is crucial to both
      real-world social functioning and abstract decision making in the laboratory
      (see, e.g., Stuss et al., ; Bechara et al., 1994; Damasio et al., ). Previous
      research has shown that the relationship between the laterality of individuals'
      vmPFC lesions and neuropsychological performance is moderated by their sex,
      whereby there are more severe social, emotional, and decision-making impairments
      in men with right-side vmPFC lesions and in women with left-side vmPFC lesions
      (Tranel et al., 2005; Sutterer et al., 2015). We conducted a selective review of
      studies examining the effect of vmPFC lesions on emotion and decision making and
      found further evidence of sex-related differences in the lateralization of
      function not only in the vmPFC but also in other neurological structures
      associated with decision making and emotion. This Mini-Review suggests that both
      sex and laterality effects warrant more careful consideration in the scientific
      literature. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870466
TI  - Wacker Silicone Award: A. C. Filippou / Herman Skolnik Award: D. A. Winkler /
      Erwin Schrodinger Prize: C. Barner-Kowollik.

PMID- 27870465
TI  - Corrigendum: The Nucleophilicity of Persistent alpha-Monofluoromethide Anions.

PMID- 27870461
TI  - Sexual dimorphism of Broca's region: More gray matter in female brains in
      Brodmann areas 44 and 45.
AB  - Although a sexual dimorphism in brain structure is generally well established,
      evidence for sex differences in Brodmann areas (BA) 44 and 45 is inconclusive.
      This may be due to the difficulty of accurately defining BA 44 and BA 45 in
      magnetic resonance images, given that these regions are variable in their
      location and extent and that they do not match well with macroanatomic landmarks.
      Here we set out to test for possible sex differences in the local gray matter of
      BA 44/45 by integrating imaging-based signal intensities with
      cytoarchitectonically defined tissue probabilities in a sample of 50 male and 50
      female subjects. In addition to testing for sex differences with respect to left-
      and right-hemispheric measures of BA 44/45, we also assessed possible sex
      differences in BA 44/45 asymmetry. Our analyses revealed significantly larger
      gray matter volumes in females compared with males for BA 44 and BA 45
      bilaterally. However, there was a lack of significant sex differences in BA 44/45
      asymmetry. These results corroborate reports of a language-related female
      superiority, particularly with respect to verbal fluency and verbal memory tasks.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27870467
TI  - Nontraditional pi Gelators Based on beta-Iminoenolate and Their Difluoroboron
      Complexes: Effect of Halogens on Gelation and Their Fluorescent Sensory
      Properties Towards Acids.
AB  - We have synthesized a series of new beta-iminoenolates and their corresponding
      difluoroboron complexes without any traditional gelation moieties, and some of
      them were able to gelatinize organic solvents. It was found that the presence of
      halogen atoms as substituents had a significant effect on gelation ability. In
      particular, bromo-containing compounds 4 A and 4 B exhibited excellent gelation
      abilities compared with other halogen-substituted gelators. By analyses of the
      single-crystal structure, the PXRD pattern of the xerogel, and electronic
      spectral changes during gelation, we deemed that pi-pi, C-H???F, and C-H???Br
      interactions were the driving forces for the gelation of 4 B. Interestingly, (Z)
      1-(4-bromophenyl)-2-(3-methylpyrazin-2-yl)ethen-1-ol (8 A), prepared in this
      work, is the lowest-molecular-weight organogelator to have been reported. It
      should be noted that although beta-iminoenolates 3 A-5 A are nonemissive in
      solution, they emit strong yellow light in organogels, which suggests aggregation
      induced emissive activity, whereas the difluoroboron complexes 3 B-5 B show
      strong fluorescence in solutions, organogels, and xerogel-based films. Moreover,
      we found that the emission of 4 B in a nanofiber-based film could be quenched
      significantly upon exposure to gaseous trifluoroacetic acid and that the decay
      time and detection limit were 0.5 s and 0.17 ppm, respectively. Thus, through
      this work we have provided a new strategy for the design of nontraditional pi
      gelators by introducing halogen atoms into pi-conjugated systems with moderate
      polarities.

PMID- 27870468
TI  - MicroRNA Profile in Cerebrospinal Fluid and Plasma of Patients with Spontaneous
      Intracerebral Hemorrhage.

PMID- 27870469
TI  - A panel of circulating miRNAs as diagnostic biomarkers for screening multiple
      myeloma: a systematic review and meta-analysis.
AB  - Circulating microRNAs (miRNAs) have been proved to be effective diagnostic
      markers for multiple myeloma (MM). The meta-analysis was aimed to evaluate the
      diagnostic value of related miRNAs. Multiple databases (PubMed, Web of Science,
      EMBASE, Cochrane Library, CBM, and CNKI) were systematically searched for
      available studies up to March 2016. All data were analyzed with the help of
      software revman 5.3 and metadisc 1.4. The eligible articles' quality was
      estimated by QUADAS-2, and pooled parameters were acquired with the bivariate
      random-effects meta-analysis model. Subgroup analysis and meta-regression were
      conducted to explore the heterogeneity of studies included. After steps of
      screening, seven qualified literatures were selected. They consisted of 22
      studies that included 486 newly diagnosed MM patients and 292 healthy controls.
      Summary receiver operating characteristic (SROC) analyses of all miRNAs showed an
      area under the curve (AUC) of 0.86 (95%CI, 0.82-0.91). Together with the AUC, the
      positive likelihood ratio-PLR 4.45 (95%CI, 3.28-6.04), negative likelihood ratio
      NLR 0.29 (95%CI, 0.24-0.35), and diagnostic odds ratio-DOR 17.59 (95%CI, 11.26
      27.4) confirmed that circulating miRNAs possessed relatively high diagnostic
      value in discriminating MM patients from healthy controls. For miRNAs combined
      together, miRNA-1308/miRNA-720 had the highest sensitivity 0.96 (95%CI, 0.79
      1.00) and specificity 0.92 (95%CI 0.64-1.0). The subgroup and meta-regression
      analyses also showed that miRNAs profiling was the sole source of heterogeneity,
      and the diagnostic accuracy of combined miRNAs was 6.02 times higher than single
      one. Combined circulating miRNAs in serum or plasma may be highly effective
      biomarker for diagnosis of MM.

PMID- 27870471
TI  - Analytical evaluation of the ADAMSTM A1c HA 8180 thalassemia mode high-pressure
      liquid chromatography analyser for the measurement of HbA2 and HbF.
AB  - BACKGROUND: ADAMSTM A1cHA-8180T is a HPLC system; within 3.5 min, it quantifies
      HbF, HbA2 , and HbA0 and flags abnormal peaks. We evaluate its analytical
      performance for routine estimation of HbA2 and HbF, and critical tests were
      performed for identifying beta-thalassemia carriers. METHODS: Trueness
      imprecision, carry over, linearity, and effect of anemia were evaluated according
      to ICLH, ICLS, or manufacture's guidelines. Comparison (ADAMSTM A1c HA-8160T) was
      performed by running 400 samples from healthy subjects, 30 alpha and 80 beta
      carriers (range: 1.9-5.7 %). RESULTS: Trueness - HbA2 2.7 %, bias 0.81 %; HbA2
      5.8 %, bias 0.38 %. HbA2 4.0% is not affected by Hb in the range 221-40 g/L.
      Carry over was negligible. Within run: normal control - CV 1.5 %, high control -
      CV 0.9 %.Within laboratory: normal control - total CV% 1.59%; high control - 0.92
      %. Linearity - y = 1.034x - 0.17, R2  = 0.998 (range: 2.8-4.8%).Method comparison
      - y = 0.93x + 0.22, R2  = 0.997. HbF imprecision CVs between 0.66 and 1.24% and
      trueness between 0 and 2.8%. Linearity - y = 1.088x - 0.27, R2  = 0.999 (0.1
      5.7%). CONCLUSIONS: ADAMSTM A1c HA-8180T provides a rapid and reliable separation
      of HbA2 . The measurement is accurate and reproducible, which is needed because
      of the slight difference between normal and pathological values. The gap in HbA2
      values between normal subjects and beta-thalassemia carriers makes this an
      appropriate method for rapid screening for carriers.

PMID- 27870472
TI  - Nodular sclerosis classical Hodgkin lymphoma grade 2: A diagnostic challenge to
      the cytopathologists.
AB  - BACKGROUND: Grade 2 nodular sclerosis classical Hodgkin lymphoma (NSCHL) is less
      common than grade 1 lymphoma and has a worse overall prognosis. To the best of
      the authors' knowledge, no study of a large series of cases has been performed
      until now. The objective of this study was to assess the diagnostic efficacy of
      cytology for grade 2 NSCHL versus grade 1 NSCHL and study the morphological
      features of grade 2 NSCHL in fine-needle aspiration cytology (FNAC). METHODS:
      Fifteen of 51 histopathology-proven cases of NSCHL (18 FNAC procedures) were
      grade 2, and 36 were grade 1. The efficacy of FNAC for detecting grade 1 and 2
      NSCHL was assessed, and the frequency of misdiagnosis was compared. The clinical
      details and cytomorphological features of grade 2 NSCHL were studied in detail.
      RESULTS: Among the grade 1 NSCHL patients, 58.4% were diagnosed with Hodgkin
      lymphoma (HL) or had findings suggestive of HL, whereas 20% of the grade 2
      patients were diagnosed HL or suggestive of HL. Two cases of grade 2 NSCHL were
      misdiagnosed as anaplastic large cell lymphoma, and 4 were misdiagnosed as
      malignant neoplasms. Grade 2 NSCHL cases showed clusters and sheets of
      mononuclear, multinucleated, and bizarre cells, with some cases showing a
      suppurative background. However, extensive searching showed occasional Reed
      Sternberg (RS) cells in most of the cases, and lacunar cells were seen in 12
      cases. CONCLUSIONS: The diagnostic efficacy of FNAC is much lower for grade 2
      NSCHL versus grade 1 NSCHL. The search for an occasional RS cell and the
      identification of lacunar cells can provide a clue for the diagnosis. Cancer
      Cytopathol 2017;125:104-113. (c) 2016 American Cancer Society.

PMID- 27870473
TI  - Development of practice guidelines for psychological interventions in the
      rehabilitation of patients with oncological disease (breast, prostate, or
      colorectal cancer): Methods and results.
AB  - OBJECTIVE: The goal of this project was to develop evidence- and consensus-based
      practice guidelines for psychological interventions in the rehabilitation of
      patients with oncological disease (breast, prostate, or colorectal cancer).
      METHODS: First of all, we conducted a literature search and survey of all
      oncological rehabilitation centers in Germany (N = 145) to obtain a thorough
      perspective of the recent evidence, guidelines, the structural framework, and
      practice of psychological services in oncological rehabilitation. Next, an expert
      workshop was held with national experts from scientific departments, clinicians
      from rehabilitation centers, and patients. In this workshop, we drafted and
      agreed upon an initial version of the practice guidelines. Afterwards, the
      practice guidelines were sent to all head physicians and senior psychologists at
      oncological rehabilitation centers in Germany for approval (N = 280
      questionnaires). In addition, key recommendations were discussed with a group of
      rehabilitation patients. Finally, the practice guidelines were revised by the
      expert panel and made available online to the public. RESULTS: The practice
      guidelines have been widely accepted by both the expert panel and the surveyed
      clinicians and patients. They include recommendations for psycho-oncological
      interventions that should be offered to all rehabilitation patients with breast,
      prostate, or colorectal cancer. They also comprise recommendations for specific
      problem areas concerning psychological functions, body functions, and
      environmental and personal factors. CONCLUSIONS: The practice guidelines provide
      detailed recommendations for high-quality psychosocial care in an oncological
      rehabilitation context. It is their aim to guide the multidisciplinary team,
      especially psychologists and physicians, in their daily practice.

PMID- 27870478
TI  - Clinical Pharmacology in Drug Development: Five Years in the Books.

PMID- 27870477
TI  - Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of
      Noribogaine in Opioid-Dependent Patients.
AB  - Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms.
      This was the first clinical trial of noribogaine, ibogaine's active metabolite,
      in patients established on methadone opioid substitution therapy (OST). In this
      randomized, double-blind, placebo-controlled single ascending-dose study, we
      evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27
      patients seeking to discontinue methadone OST who had been switched to morphine
      during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose
      level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated.
      The most frequent treatment-emergent adverse events were noneuphoric changes in
      light perception ~1 hour postdose, headache, and nausea. Noribogaine had dose
      linear increases for AUC and Cmax and was slowly eliminated (mean t1/2 range, 24
      30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL),
      with the largest observed mean effect of ~16, 28, and 42 milliseconds in the 60-,
      120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically
      significant trend toward decreased total score in opioid withdrawal ratings, most
      notably at the 120-mg dose; however, the study design may have confounded
      evaluations of time to resumption of OST. Future exposure-controlled multiple
      dose noribogaine studies are planned that will address these safety and design
      issues.

PMID- 27870479
TI  - Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite
      M12.
AB  - The pharmacokinetics of apremilast and its major metabolite M12 were evaluated in
      subjects with varying degrees of renal impairment. Men and women with renal
      impairment (estimated glomerular filtration rate, 60-89 mL/min [mild, n = 8], 30
      59 mL/min [moderate, n = 8], or <30 mL/min [severe, n = 8]) or demographically
      healthy matched (control) subjects (n = 24) received a single oral dose of
      apremilast 30 mg. Plasma apremilast and metabolite M12 concentrations were
      determined, and pharmacokinetic parameters were calculated from samples obtained
      predose and up to 72 hours postdose. In subjects with mild to moderate renal
      impairment, apremilast pharmacokinetic profiles were similar to healthy matched
      subjects. In subjects with severe renal impairment, apremilast elimination was
      significantly slower, and exposures based on area under the plasma concentration
      versus-time curve from time zero extrapolated to infinity and maximum observed
      plasma concentration were increased versus healthy matched subjects. Metabolite
      M12 pharmacokinetic profiles for subjects with mild renal impairment were similar
      to those of the healthy matched subjects; however, they were increased in both
      the moderate and severe renally impaired subjects. Dose reduction of apremilast
      is recommended in individuals with severe renal impairment, but not in those with
      mild to moderate renal impairment.

PMID- 27870480
TI  - Pharmacokinetics and Safety of Defibrotide in Healthy Japanese Subjects.

PMID- 27870482
TI  - Corrigendum.

PMID- 27870481
TI  - Glycemic Effect and Safety of a Systemic, Partial Glucokinase Activator, PF
      04937319, in Patients With Type 2 Diabetes Mellitus Inadequately Controlled on
      Metformin-A Randomized, Crossover, Active-Controlled Study.
AB  - Glucokinase enhances glucose conversion to glucose-6-phosphate, causing glucose
      stimulated insulin secretion from pancreatic beta cells and increased hepatic
      glucose uptake. PF-04937319 is a partial glucokinase activator designed to
      maintain efficacy with reduced hypoglycemia risk. In this randomized, double
      blind, double-dummy, 3-period crossover phase 1b study, patients aged 18-70 years
      with type 2 diabetes mellitus and on metformin received once-daily PF-04937319
      (300 mg), split-dose PF-04937319 (150+100 mg; breakfast+lunch), or sitagliptin
      (100 mg once daily). The primary end point was day 14 weighted mean daily glucose
      (WMDG) change from period-specific baseline. Secondary end points included change
      from baseline in fasting plasma glucose, premeal C-peptide and insulin, and
      safety, including hypoglycemia frequency. Mean decrease from baseline in observed
      WMDG (mg/dL) was greater for PF-04937319 (split-dose, -31.24; once daily, -31.33)
      versus sitagliptin (-19.24). Using the integrated glucose red-cell HbA1c model,
      the observed WMDG effect with both PF-04937319 dosing regimens was projected to
      yield a clinically superior effect on mean glycated hemoglobin (HbA1c ; split
      dose, -0.88%; once daily, -0.94%) compared with sitagliptin (-0.63%). There was
      no difference in premeal C-peptide or insulin levels, and although the effect on
      WMDG with both PF-04937319 regimens was similar, the split-dose regimen appeared
      to offer some advantage in safety and tolerability.

PMID- 27870483
TI  - Transcriptome analysis of the regenerating tail vs. the scarring limb in lizard
      reveals pathways leading to successful vs. unsuccessful organ regeneration in
      amniotes.
AB  - BACKGROUND: Lizards are amniotes regenerating the tail but not the limb, and no
      information on their different gene expression is available. RESULTS:
      Transcriptomes of regenerating tail and limb blastemas show differences in gene
      expression between the two organs. In tail blastemal, snoRNAs and Wnt signals
      appear up-regulated probably in association with the apical epidermal peg (AEP),
      an epithelial region that sustains tail regeneration but is absent in the limb. A
      balance between pro-oncogenes and tumor suppressors is likely present in tail
      blastema allowing a regulated proliferation. Small collagens, protease
      inhibitors, embryonic keratins are up-regulated in the regenerating tail blastema
      but not in the limb where Wnt inhibitors, inflammation-immune and extracellular
      matrix proteins depress cell growth. CONCLUSIONS: The AEP and the spinal cord in
      the tail maintains Wnt and fibroblast growth signaling that stimulate blastema
      cell proliferation and growth while these signals are absent in the limb as a
      consequence of the intense inflammation. Regeneration of amniote appendages
      requires a control of cell proliferation and inflammatory-immune reactions to
      form an apical epidermal cap. Genes that control cell proliferation and
      inflammation, addressing regeneration and not tumor formation in the tail and
      scarring in the limb are discussed for future studies. Developmental Dynamics
      246:116-134, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27870484
TI  - GUEST EDITORIAL.

PMID- 27870485
TI  - Nomenclature for factors of the HLA system, update August 2016.

PMID- 27870486
TI  - Nomenclature for factors of the HLA system, update July 2016.

PMID- 27870488
TI  - Nomenclature for factors of the HLA system, update September 2016.

PMID- 27870489
TI  - Intraocular lens power calculation in primary angle closure.

PMID- 27870487
TI  - Identification of a novel HLA-C*06 variant allele, HLA-C*06:166, by sequence
      based typing in a Chinese individual.
AB  - HLA-C*06:166 differs from HLA-C*06:02:01:01 (146T -> C, exon 2, V25A).

PMID- 27870491
TI  - Continuing Professional Development.

PMID- 27870490
TI  - Peeking into the molecular trove of discarded surgical specimens.

PMID- 27870492
TI  - Authors beware! The rise of the predatory publisher.

PMID- 27870493
TI  - Monday 21 November.

PMID- 27870495
TI  - Past Lecturers and Briefs for the Named Lectures: RANZCO Annual Scientific
      Congress.

PMID- 27870494
TI  - Film Abstracts.

PMID- 27870496
TI  - Sunday 20 November.

PMID- 27870498
TI  - Wednesday 23 November.

PMID- 27870499
TI  - Invited Speakers.

PMID- 27870500
TI  - Tuesday 22 November.

PMID- 27870504
TI  - Chronic LiCl pretreatment suppresses thrombin-stimulated intracellular calcium
      mobilization through TRPC3 in astroglioma cells.
AB  - OBJECTIVES: Transient receptor potential canonical type 3 (TRPC3) channels are
      activated in B lymphoblast cell lines from patients with bipolar disorder (BD),
      and its expression is reduced by chronic lithium treatment, implicating TRPC3 in
      the intracellular calcium (Ca2+ ) dyshomeostasis of BD. Thrombin, via a protease
      activated receptor, moderates Ca2+ signaling and TRPC3 in astrocytes, and also
      cell proliferation. We examined whether lithium pretreatment attenuates thrombin
      stimulated TRPC3 expression and function in astrocytes, and levels of the calcium
      binding peptide, S100B, which is expressed mainly in these cells. METHODS: Human
      astroglioma, U-87MG, cells were pretreated with 1 mmol L-1 LiCl for 1 day
      (acute), 3 days (subacute), and 7 days (chronic). To examine the role of TRPC3,
      genetically stable knockdown TRPC3 cells (TRPC3Low cells) were constructed using
      U-87MG cells. Thrombin (2.0 U/mL)-stimulated Ca2+ mobilization was measured by
      ratiometric fluorimetry. Changes in TRPC3 and S100B expression levels were
      determined by quantitative reverse transcription-polymerase chain reaction and
      immunoblotting, respectively. Cell proliferation was also measured using the WST
      8 assay. RESULTS: In this cell model, thrombin-stimulated Ca2+ mobilization, and
      both TRPC3 and S100B expression were suppressed by chronic LiCl pretreatment and
      the knockdown of TRPC3. Additionally, cell proliferation was attenuated in
      TRPC3Low cells, compared with the negative control vector-transfected cell.
      CONCLUSIONS: The reduced Ca2+ mobilization and S100B expression levels following
      chronic LiCl pretreatment and in TRPC3Low cells support the notion that TRPC3
      modulates S100B expression and is the target of the LiCl effect. Downregulation
      of TRPC3 may be an important mechanism by which lithium ameliorates
      pathophysiological intracellular Ca2+ disturbances as observed in BD, accounting,
      in part, for its mood-stabilizing effects.

PMID- 27870505
TI  - Distinguishing medication-free subjects with unipolar disorder from subjects with
      bipolar disorder: state matters.
AB  - OBJECTIVES: Recent studies have indicated that pattern recognition techniques of
      functional magnetic resonance imaging (fMRI) data for individual classification
      may be valuable for distinguishing between major depressive disorder (MDD) and
      bipolar disorder (BD). Importantly, medication may have affected previous
      classification results as subjects with MDD and BD use different classes of
      medication. Furthermore, almost all studies have investigated only depressed
      subjects. Therefore, we focused on medication-free subjects. We additionally
      investigated whether classification would be mood state independent by including
      depressed and remitted subjects alike. METHODS: We applied Gaussian process
      classifiers to investigate the discriminatory power of structural MRI (gray
      matter volumes of emotion regulation areas) and resting-state fMRI (resting-state
      networks implicated in mood disorders: default mode network [DMN], salience
      network [SN], and lateralized frontoparietal networks [FPNs]) in depressed (n=42)
      and remitted (n=49) medication-free subjects with MDD and BD. RESULTS: Depressed
      subjects with MDD and BD could be classified based on the gray matter volumes of
      emotion regulation areas as well as DMN functional connectivity with 69.1%
      prediction accuracy. Prediction accuracy using the FPNs and SN did not exceed
      chance level. It was not possible to discriminate between remitted subjects with
      MDD and BD. CONCLUSIONS: For the first time, we showed that medication-free
      subjects with MDD and BD can be differentiated based on structural MRI as well as
      resting-state functional connectivity. Importantly, the results indicated that
      research concerning diagnostic neuroimaging tools distinguishing between MDD and
      BD should consider mood state as only depressed subjects with MDD and BD could be
      correctly classified. Future studies, in larger samples are needed to investigate
      whether the results can be generalized to medication-naive or first-episode
      subjects.

PMID- 27870503
TI  - The role of type II transmembrane serine protease-mediated signaling in cancer.
AB  - Pericellular proteases have long been implicated in carcinogenesis. Previous
      research focused on these proteins, primarily as extracellular matrix (ECM)
      protein-degrading enzymes which allowed cancer cells to breach the basement
      membrane and invade surrounding tissue. However, recently, there has been a shift
      in the view of cell surface proteases, including serine proteases, as proteolytic
      modifiers of particular targets, including growth factors and protease-activated
      receptors, which are critical for the activation of oncogenic signaling pathways.
      Of the 176 human serine proteases currently identified, a subset of 17, known as
      type II transmembrane serine proteases (TTSPs). Many have been shown to be
      relevant to cancer progression since they were first identified as a family
      around the turn of the century. To this end, altered expression of TTSPs appeared
      as a trademark of several tumor types. However, the substrates and underlying
      signaling pathways remained unclear. Localization of these proteins to the cell
      surface places them in the unique position to mediate signal transduction between
      the cell and its surrounding environment. Many of the TTSPs have already been
      shown to play key roles in processes such as postnatal development, tissue
      homeostasis, and tumor progression, which share overlapping molecular mechanisms.
      In this review, we summarize the current knowledge regarding the role of the TTSP
      family in pro-oncogenic signaling.

PMID- 27870506
TI  - Differential neurometabolite alterations in brains of medication-free individuals
      with bipolar disorder and those with unipolar depression: a two-dimensional
      proton magnetic resonance spectroscopy study.
AB  - OBJECTIVES: Bipolar disorder (BD) is a mental disorder characterized by periods
      of elevated mood and depression. Many individuals with BD are initially
      misdiagnosed and treated for unipolar depression (UD). In this study, we report
      direct comparisons between medication-free individuals with BD and those with UD
      in terms of the neurometabolites in the anterior cingulate cortex (ACC), medial
      prefrontal cortex (mPFC), parietal cortex (PC), and posterior cingulate cortex
      (PCC) of the brain. METHODS: Participants included medication-free patients with
      BD or UD, and matched healthy controls. All patients were in the depressive state
      and had similar symptoms. All subjects were subjected to a multi-voxel proton
      magnetic resonance spectroscopy procedure with a 3.0 T GE Signa MR scanner. After
      post-processing, the absolute concentrations of glycerophosphocholine +
      phosphocholine (GPC + PC), phosphocreatine + creatine (PCr + Cr), Glx (glutamate
      + glutamine), myo-inositol (MI), and N-acetyl aspartate (NAA) from the above
      brain regions were compared across the three groups. RESULTS: Patients with BD
      showed significantly higher levels of Glx in their ACC, lower GPC + PC, PCr + Cr,
      MI, and NAA in their PC, and lower NAA in their mPFC, compared to healthy
      controls; patients with UD presented significantly lower levels of GPC + PC, PCr
      + Cr, and NAA in their PCC, and lower Glx in their mPFC. All analyzed brain
      metabolites, except Glx, were significantly lower in the PC of patients with BD,
      whereas levels of GPC + PC, PCr + Cr, and NAA were significantly reduced in the
      PCC of patients with UD. CONCLUSIONS: These results add to the evidence of brain
      metabolite differences in brains of patients with UD and BD which may be of help
      in differentiating these two mood disorders.

PMID- 27870508
TI  - 2016 ACR/ARHP Annual Meeting Abstract Supplement.
AB  - For a searchable version of these abstracts, please visit www.acrabstracts.org.

PMID- 27870507
TI  - Stress and reward processing in bipolar disorder: a functional magnetic resonance
      imaging study.
AB  - OBJECTIVES: A link between negative life stress and the onset of mood episodes in
      bipolar disorder (BD) has been established, but processes underlying such a link
      remain unclear. Growing evidence suggests that stress can negatively affect
      reward processing and related neurobiological substrates, indicating that a
      dysregulated reward system may provide a partial explanation. The aim of this
      study was to test the impact of stress on reward-related neural functioning in
      BD. METHODS: Thirteen euthymic or mildly depressed individuals with BD and 15
      controls performed a Monetary Incentive Delay (MID) task while undergoing
      functional magnetic resonance imaging during no-stress and stress (negative
      psychosocial stressor involving poor performance feedback and threat of monetary
      deductions) conditions. RESULTS: In hypothesis-driven region-of-interest
      analyses, a significant group-by-condition interaction emerged in the amygdala
      during reward anticipation. Relative to controls, while anticipating a potential
      reward, subjects with BD were characterized by amygdalar hyperactivation in the
      no-stress condition but hypoactivation during stress. Moreover, relative to
      controls, subjects with BD had significantly larger amygdala volumes. After
      controlling for structural differences, the effects of stress on amygdalar
      function remained, whereas groups no longer differed during the no-stress
      condition. During reward consumption, a group-by-condition interaction emerged in
      the putamen due to increased putamen activation in response to rewards in
      participants with BD during stress, but an opposite pattern in controls.
      CONCLUSIONS: Overall, findings highlight possible impairments in using reward
      predicting cues to adaptively engage in goal-directed actions in BD, combined
      with stress-induced hypersensitivity to reward consumption. Potential clinical
      implications are discussed.

PMID- 27870509
TI  - Frailty and sarcopenia in subjects with Alzheimer's disease with or without
      cerebrovascular disease.

PMID- 27870511
TI  - Unusual occurrence of a rare mandibular lesion mimicking an osseous cyst.

PMID- 27870510
TI  - Neuropsychological differences in Alzheimer's disease patients with or without
      type 2 diabetes mellitus.

PMID- 27870513
TI  - International Wound Journal 2016: a year in review.

PMID- 27870516
TI  - Editors' Notes.

PMID- 27870515
TI  - Internalization of Dominance and Subordination: Barriers to Creative and
      Intellectual Fullness.
AB  - This chapter explores the ways in which identities and positions of dominance or
      subordination in a societal system of power and privilege affect the way in which
      leadership is enacted.

PMID- 27870517
TI  - Culturally Responsive Integrative Learning Environments: A Critical Displacement
      Approach.
AB  - This chapter outlines a critical framework for developing culturally responsive
      integrative learning environments in leadership education. The framework is
      grounded in the scholarship of women of color feminism and offers implications
      for transforming curricular and cocurricular leadership programs.

PMID- 27870518
TI  - Preparing Interfaith Leaders: Knowledge Base and Skill Set for Interfaith
      Leaders.
AB  - This chapter gives an overview of the vision, knowledge base, and skill set of
      interfaith leadership.

PMID- 27870519
TI  - The Practice of Freedom: Leading Through Controversy.
AB  - Theoretical frameworks, specific skills for leaders, and guidance to effectively
      work with others across difference as well as practice freedom to facilitate
      transformational social movements are explored in this chapter.

PMID- 27870520
TI  - Authenticity in Leadership: Intersectionality of Identities.
AB  - This chapter situates leadership and the process of becoming a leader within an
      understanding of identity, particularly intersecting social identities and
      intersectionality.

PMID- 27870521
TI  - Leading to Transgress: Critical Considerations for Transforming Leadership
      Learning.
AB  - The culturally relevant leadership learning (CRLL) model is explored through the
      lens of theory and practice. This creates critical questions to guide leadership
      educators in the ongoing process of transforming leadership programs.

PMID- 27870522
TI  - Critical Domains of Culturally Relevant Leadership Learning: A Call to Transform
      Leadership Programs.
AB  - This chapter introduces the critical domains of culturally relevant leadership
      learning. The model explores how capacity, identity, and efficacy of student
      leaders interact with dimensions of campus climate.

PMID- 27870523
TI  - Leadership Lessons from Communities of Color: Stewardship and Collective Action.
AB  - This chapter proposes a multicultural leadership model that reflects practices
      and principles from Black, Latino, and American Indian communities.

PMID- 27870524
TI  - AANP NEWS.

PMID- 27870525
TI  - The case for academic detailing with nurse practitioners.

PMID- 27870526
TI  - Dimensions of medication adherence in African Americans with type 2 diabetes in
      rural North Carolina.

PMID- 27870527
TI  - Indirect Exposure to Captivity Details Is Not Related to Posttraumatic Stress
      Symptoms Among the Spouses and Offspring of Former Prisoners of War.
AB  - Indirect exposure to the aversive details of the primary victim's traumatic
      event(s) has been introduced in the fifth edition of the Diagnostic and
      Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association,
      2013) as a new event criterion (Criterion A4). However, this new criterion has
      been criticized for its significant emphasis on the exposure to trauma "details"
      or trauma narrative. This study assessed the associations between reported
      exposure to details about captivity and posttraumatic stress symptoms (PTSS)
      among 2 groups of family members of former prisoners of war (ex-POWs): spouses (n
      = 115) and adult offspring (n = 78). Results show that in both groups exposure to
      details regarding captivity was not significantly related to the severity of
      total PTSS and specifically, high levels of exposure to captivity details were
      related to lower avoidance symptoms among ex-POWs' spouses. Among offspring,
      exposure to paternal behaviors stemming from the fathers' posttraumatic stress
      disorder was related to PTSS, above and beyond negative life events, quality of
      relationship with the father, and exposure to captivity details (R2 = .34). These
      results suggest that behavioral displays of the fathers' posttraumatic symptoms,
      rather than the recounting of trauma-related details, is related to PTSS among ex
      POWs' offspring.

PMID- 27870528
TI  - Catalytically Triggered Energy Release from Strained Organic Molecules: The
      Surface Chemistry of Quadricyclane and Norbornadiene on Pt(111).
AB  - We have investigated the surface chemistry of the polycyclic valence-isomer pair
      norbornadiene (NBD) and quadricyclane (QC) on Pt(111). The NBD/QC system is
      considered to be a prototype for energy storage in strained organic compounds. By
      using a multimethod approach, including UV photoelectron, high-resolution X-ray
      photoelectron, and IR reflection-absorption spectroscopic analysis and DFT
      calculations, we could unambiguously identify and differentiate between the two
      molecules in the multilayer phase, which implies that the energy-loaded QC
      molecule is stable in this state. Upon adsorption in the (sub)monolayer regime,
      the different spectroscopies yielded identical spectra for NBD and QC at 125 and
      160 K, when multilayer desorption takes place. This behavior is explained by a
      rapid cycloreversion of QC to NBD upon contact with the Pt surface. The NBD
      adsorbs in a eta2 :eta1 geometry with an agostic Pt-H interaction of the
      bridgehead CH2 subunit and the surface. Strong spectral changes are observed
      between 190 and 220 K because the hydrogen atom that forms the agostic bond is
      broke. This reaction yields a norbornadienyl intermediate species that is stable
      up to approximately 380 K. At higher temperatures, the molecule dehydrogenates
      and decomposes into smaller carbonaceous fragments.

PMID- 27870529
TI  - Infections and exposure to anti-infective agents and the risk of severe mental
      disorders: a nationwide study.
AB  - OBJECTIVE: Severe infections are associated with increased risks of mental
      disorders; however, this is the first large-scale study investigating whether
      infections treated with anti-infective agents in the primary care setting
      increase the risks of schizophrenia and affective disorders. METHOD: We
      identified all individuals born in Denmark 1985-2002 (N = 1 015 447) and studied
      the association between infections treated with anti-infective agents and the
      subsequent risk of schizophrenia and affective disorders during 1995-2013. Cox
      regression analyses were adjusted for important confounders. RESULTS: Infections
      treated with anti-infective agents were associated with increased risks of
      schizophrenia by a hazard rate ratio (HRR) of 1.37 (95%-CI = 1.20-1.57) and
      affective disorders by a HRR of 1.64 (95%-CI = 1.48-1.82), fitting a dose
      response and temporal relationship (P < 0.001). The excess risk was primarily
      driven by infections treated with antibiotics, whereas infections treated with
      antivirals, antimycotics, and antiparasitic agents were not significant after
      mutual adjustment. Individuals with infections requiring hospitalization had the
      highest risks for schizophrenia (HRR = 2.05; 95%-CI = 1.77-2.38) and affective
      disorders (HRR = 2.59; 95%-CI = 2.31-2.89). CONCLUSION: Infections treated with
      anti-infective agents and particularly infections requiring hospitalizations were
      associated with increased risks of schizophrenia and affective disorders, which
      may be mediated by effects of infections/inflammation on the brain, alterations
      of the microbiome, genetics, or other environmental factors.

PMID- 27870530
TI  - Coiled-Coil-Mediated Activation of Oligoarginine Cell-Penetrating Peptides.
AB  - A supramolecular approach was undertaken to create functionally activatable cell
      penetrating peptides. Two tetra-arginines were assembled into an active cell
      penetrating peptide by heterodimerizing leucine zippers. Three different leucine
      zipper pairs were evaluated: activation was found to depend on the association
      constant of the coiled-coil peptides. The weaker-binding peptides required an
      additional disulfide linkage to induce cell-penetrating capability, whereas for
      the most-stable coiled-coil no additional stabilization was needed. The latter
      zipper pair was used to show that the induced formation of the coiled coils
      allows control over the uptake of an oligoarginine CPP-conjugated cargo protein.

PMID- 27870531
TI  - Evaluation of an innovative hands-on anatomy-centered ultrasound curriculum to
      supplement graduate gross anatomy education.
AB  - Ultrasound (US) can enhance anatomy education, yet is incorporated into few non
      medical anatomy programs. This study is the first to evaluate the impact of US
      training in gross anatomy for non-medical students in the United States. All 32
      master's students enrolled in gross anatomy with the anatomy-centered ultrasound
      (ACUS) curriculum were recruited. Mean Likert ratings on pre- and post-course
      surveys (100% response rates) were compared to evaluate the effectiveness of the
      ACUS curriculum in developing US confidence, and gauge its impact on views of US.
      Post-course, students reported significantly higher (P < 0.001) mean confidence
      ratings in five US skills (pre-course versus post-course mean): obtaining scans
      (3.13 +/-1.04 versus 4.03 +/-0.78), optimizing images (2.78 +/-1.07 versus 3.75
      +/-0.92), recognizing artifacts (2.94 +/-0.95 versus 3.97 +/-0.69),
      distinguishing tissue types (2.88 +/-0.98 versus 4.09 +/-0.69), and identifying
      structures (2.97 +/-0.86 versus 4.03 +/-0.59), demonstrating the success of the
      ACUS curriculum in students with limited prior experience. Views on the value of
      US to anatomy education and to students' future careers remained positive after
      the course. End-of-semester quiz performance (91% response rate) provided data on
      educational outcomes. The average score was 79%, with a 90% average on questions
      about distinguishing tissues/artifacts, demonstrating positive learning outcomes
      and retention. The anatomy-centered ultrasound curriculum significantly increased
      confidence with and knowledge of US among non-medical anatomy students with
      limited prior training. Non-medical students greatly value the contributions that
      US makes to anatomy education and to their future careers. It is feasible to
      enhance anatomy education outside of medical training by incorporating US. Anat
      Sci Educ 10: 348-362. (c) 2016 American Association of Anatomists.

PMID- 27870532
TI  - Distinguishing the Protonation State of the Histidine Ligand to the Oxidized Iron
      Sulfur Cluster from the MitoNEET Family of Proteins.
AB  - The iron-sulfur cluster located in the recently discovered human mitoNEET protein
      (and related proteins) is structurally similar to the more well-known ferredoxin
      and Rieske clusters. Although its biological function is uncertain, the iron
      sulfur cluster in mitoNEET has been proposed to undergo proton-coupled electron
      transfer involving the histidine ligand to the cluster. The cluster is also
      released from the protein at low pH. This contribution reports density functional
      calculations to model the structures, vibrations, and Heisenberg coupling
      constants (J) for high-spin (HS), broken symmetry (BS) singlet, and extended
      broken symmetry (EBS) singlet states of the oxidized iron-sulfur cluster from
      mitoNEET. This work suggests that J values or 15 N isotopic frequency shifts may
      provide methods for determining experimentally whether the histidine ligand to
      the oxidized iron-sulfur cluster in human mitoNEET and mitoNEET-related proteins
      is protonated or deprotonated.

PMID- 27870535
TI  - Re-visiting Fc-receptor blocking maneuvers in man.

PMID- 27870533
TI  - Set Them Free!

PMID- 27870536
TI  - Teaching advanced flow cytometry in Africa: 10 years of lessons learned.

PMID- 27870537
TI  - Structural elucidation of koumine metabolites by accurate mass measurements using
      high-performance liquid chromatography/quadrupole-time-of-flight mass
      spectrometry.
AB  - RATIONALE: Koumine is one of the major components of total alkaloids from
      Gelsemium. Koumine possesses a variety of interesting pharmacological effects,
      including anti-tumor, anti-inflammatory, and anxiolytic activities. It might be a
      promising lead drug because of its pharmacological activities and mild toxicity.
      However, little information is available on the metabolism of koumine. METHODS: A
      rapid and accurate high-performance liquid chromatography/quadrupole-time-of
      flight (HPLC/QqTOF) mass spectrometry method was applied to characterize koumine
      metabolites. Multiple scans of koumine metabolites, which were formed in rat
      liver S9, were automatically performed simultaneously through auto MS/MS mode
      acquisition in only a 30-min analysis. The structural elucidation of these
      metabolites was performed by comparing their changes in accurate molecular masses
      and product ions with those of the parent drug or metabolites. RESULTS: As a
      result, a total of eleven metabolites of koumine were identified, of which nine
      new metabolites were found. The present results showed that the N
      demethylenation, hydrogenation and the oxidation were the three main metabolic
      pathways of koumine. CONCLUSIONS: This was the first investigation of in vitro
      metabolism of koumine in rat liver S9 using a sensitive and specific HPLC/QqTOF
      MS method. The possible metabolic pathways of koumine were tentatively proposed
      based on the structural elucidations of these metabolites. This work may be
      useful in the in vivo metabolism of koumine in animals and humans. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27870538
TI  - Foodborne infections and intoxications in Poland in 2014
AB  - AIM: The purpose of the study is to assess the epidemiological situation of food
      poisonings and infections in Poland in 2014. MATERIALS AND METHODS: The
      evaluation was based on the analysis of information sent to Department of
      Epidemiology NIPH-NIH through ROE (Pol. Rejestr Ognisk Epidemicznych)- an
      electronic system created for uploading, transfer and analysis of data acquired
      during the outbreak investigations). Additional sources for the analysis were
      NIZP-PZH annual bulletins (Czarkowski MP et al. "Infectious diseases and
      poisonings in Poland", 2006-2014. Warsaw, NIPH-NIH and GIS). RESULTS: In 2014 for
      the first time in many years an increase in the number of infections and
      intoxications with bacterial etiology was observed. The number of viral foodborne
      infections was still increasing, which points towards this trend persisting.In
      2014 a total number of 533 foodborne infections and intoxications outbreaks were
      reported in which 10 754 persons were exposed and 5 494 (including 1 891 children
      up to 14 years of age) got sick. Hospitalization was required for 1 687 patients.
      The most frequent etiological agent in those outbreaks were those of viral origin
      (among which rotavirus was the most frequent agent - 25%, 3 of outbreaks and
      15.7% of cases). Salmonella spp. was responsible for 32.8 % of outbreaks and 22.6
      % of cases, and in 20.1% of outbreaks no etiological agent was found. Just as in
      2013 private household was the most frequent place of an outbreak (249
      outbreaks), and after that- hospital (130 outbreaks). In 2014 the most frequent
      vehicle were cakes and desserts (25.6% of all outbreaks with known etiological
      agent). In 84.4% no vehicle was found. Moreover in 2014 a total number of 3
      outbreaks in which more than 100 cases were reported. CONCLUSIONS: The increase
      in the number of foodborne outbreaks of viral etiology shows the need of
      adjustment some aspects of epidemiological investigations especially such
      features as: laboratory conformation of etiological agent of ill persons as well
      as persons involved in the food processing and meals preparing and the aspect of
      food samples testing.

PMID- 27870539
TI  - Hepatitis C in Poland in 2014
AB  - INTRODUCTION: . Currently, hepatitis C (HCV infection) is one of the public
      health priorities worldwide.It is associated with a considerable improvement of
      methods undertaken to eliminate this disease. Due to thepredominance of chronic
      infections of long asymptomatic course, the number of cases detected in
      successiveyears does not reflect the actual dynamics of the epidemiological
      situation of hepatitis C. To a large extent, itdepends on current testing
      practices. The modifications in the provisions on the notification of diagnosed
      casesmay also have an effect on the number of HCV infections registered in
      successive years. OBJECTIVE: This article aims at evaluating the epidemiological
      situation of HCV infections in Poland in 2014 in reference to the data from
      previous years. MATERIAL AND METHODS: Analysis of epidemiological situation of
      hepatitis C in Poland was carried out on a basis of aggregated data from routine
      surveillance system published in annual bulletin "Infectious diseases and
      poisonings in Poland". Data on hepatitis C mortality from the Demographic Surveys
      and Labour Market Department of the Central Statistical Officewere also employed.
      RESULTS: In 2014, a total of 3 076 HCV infections (incidence - 7.99 per 100,000)
      meeting 2005 definition were registered. Compared to 2013 and median as of 2008
      2012, there was an increase of the incidence by 14% (2 705; 6.03) and 34% (2 294;
      5.85), respectively. In 2014, a total of 3 551 (9.23) HCV infections meeting 2009
      definition were reported (the definition was modified in 2014). Compared to 2013
      (2 268; 6.86), it was an increase by 35%. In 2014, 241 deaths due to hepatitis C
      were registered which is the highest mortality noted so far. CONCLUSIONS: In
      recent years, a burden resulting from undiagnosed or untreated HCV infections is
      on the increase. It is demonstrated by increasing hepatitis C mortality and
      increasing trend of incidence according to 2005 definition (presence of
      symptoms). Increase of incidence according to 2009/2014 definition may be
      associated with the fact that laboratories were obliged to report positive test
      results for HCV since 2014.

PMID- 27870540
TI  - Lyme disease in Poland in 2014
AB  - INTRODUCTION: Lyme disease is the most common tick-borne disease, caused by
      spirochetes of the Borrelia genus transmitted by ticks of the Ixodes genus.
      Infection caused by Borrelia burgdorferi occur throughout Poland and therefore,
      according also to ECDC description, the whole country should be considered as an
      endemic area. OBJECTIVES: The aim of this study was to assess the epidemiological
      situation of Lyme disease in Poland in 2014 in comparison to the previous years.
      MATERIALS AND METHODS: The descriptive analysis was based on data retrieved from
      routine mandatory surveillance system and published in the annual bulletin
      "Infectious diseases and poisonings in Poland in 2014" (MP Czarkowski et al.,
      Warsaw 2015, NIZP-PZH, GIS). RESULTS: The number of cases of Lyme disease in
      recent years is steadily increasing. In total, 13.870 cases of Lyme disease
      registered in Poland in 2014, i.e. 8% more cases than in the previous year. The
      overall incidence in the country was 36.0 per 100,000 population. The highest
      incidence rate was recorded in Podlaskie voivodeship - 106.8 per 100,000. In
      2014, 2.236 people were hospitalized due to Lyme disease. SUMMARY AND
      CONCLUSIONS: In 2014, the growth rate of incidence decreased significantly. 8%
      more cases were registered compared with the previous year. There is still a need
      for bringing awareness of the need for diagnostic laboratory testing according to
      recommendations.

PMID- 27870542
TI  - A new chapter in health reform.

PMID- 27870541
TI  - Rabies in Poland in 2013 and 2014
AB  - OBJECTIVE: Evaluation of the epidemiological situation of rabies in Poland in
      2013 and 2014 in comparison to the previous years. MATERIAL AND METHODS: The
      evaluation was based on analysis of the data from individual report sent by the
      Epidemiological-Sanitary Stations. The data are from questionnaires of persons
      who were administered vaccine against rabies following exposure in Poland and
      beyond its territory, data from annual bulletin "Infectious diseases and
      poisonings in Poland in 2012-2014"(Czarkowski MP et al., Warsaw, NIH and CSI) and
      epizootic data provided by the General Veterinary Inspectorate. RESULTS: Number
      of animal rabies cases reported in Poland in 2013 and in 2014 was 204 and 105,
      respectively. This was 30% and 60% less compared to 2012. In 2013 more than 59%
      of animal rabies cases occurred in Podkarpackie veivodeship and more than 28% in
      Malopolskie. In 2014 more than 77% of rabid animals were found in the Malopolskie
      veivodeship, but Podkarpackie accounted for less than 9%. Rabies in terrestrial
      animals in 2013-2014 was also found in Lubelskie, Podlaskie and Swietokrzyskie
      veivodeships. In other regions of the country there were reported only single
      cases of rabies in bats. In 2013, a total of 7 317 people were vaccinated against
      rabies in 2013 and 7 679 in 2014 including 295 (4%) and 145 (1.9%) persons
      vaccinated due to exposure to the animals with confirmed rabies, respectively.
      Among those vaccinated after contact with rabid animal 26% and 29% were
      vaccinated after contact with a fox in 2013 and 2014, respectively and 64% and
      57% as a result of exposure to the domestic animals with confirmed rabies. As
      with the previous years, people were vaccinated mostly due to exposure to dogs
      and cats, in which rabies could not be excluded - 5 725 people in 2013 (88%) and
      6 057 (87%) in 2014. CONCLUSIONS: After the increase in the number of animal
      rabies cases that occurred in 2012, in the next two years there has been a
      gradual decline in its number. In 2014 the number of animal rabies cases was
      lower than in the 2011 and in the 2010. Epizootic situation in the country has
      inadequate impact on the number of people vaccinated against rabies who had
      contact with an animal which potentially is a source of rabies virus. This number
      for many years is consistently stable, amounting to 7 000 vaccinated individuals
      per year.

PMID- 27870543
TI  - Enhancing patient and family engagement through Meaningful Use Stage 3:
      opportunities and barriers to implementation.
AB  - OBJECTIVES: The proposed Patient and Family Engagement objectives for Meaningful
      Use Stage 3 (MU3) seek to provide patients with increased access to, and control
      over, the content and dissemination of their electronic health record (EHR)
      information. STUDY DESIGN: Implementation study conducted from 2013-2014.
      METHODS: In this study, 2 leading US health systems attempted to implement 4
      draft MU3 objectives within their current EHR system. Senior staff provided
      qualitative feedback on their implementation experience; researchers used content
      analysis to identify major themes and implementation challenges. RESULTS: We
      found that the draft objectives would support the MU3 Patient and Family
      Engagement goals, but that all objectives would benefit from the following:
      changes in policy language to promote flexibility in implementation; training and
      workflow adaptions, as well as patient education, by healthcare organizations;
      and new EHR functionalities. CONCLUSIONS: In the short term, a semi-automated
      approach is likely necessary to support MU3 objective implementation. These
      challenges are not unique to MU3 and underscore gaps in the current health
      information infrastructure.

PMID- 27870544
TI  - Referrals and the PCMH: how well do we know our neighborhood?
AB  - OBJECTIVES: Characterize patterns of referral from a patient-centered medical
      home (PCMH) and observe the association of provider experience, patient chronic
      disease burden, and risk of utilization on referral placement. STUDY DESIGN:
      Descriptive analysis of referral patterns in an academic, internal medicine PCMH.
      METHODS: We examined referrals (eg, specialist visit, testing, ancillary
      services) placed between July and December of 2014 in an academic PCMH caring for
      a total of 12,000 patients. All referrals originated from the outpatient PCMH
      clinic and were divided into resident or faculty clinic based on the assigned
      primary care provider. Patients with a referral during the 6-month study period
      served as the unit of analysis, and we developed a generalized linear model to
      identify variables associated with referral placement. We estimated the
      association of the patients' risk of healthcare utilization using a risk
      stratification tool. RESULTS: The faculty placed 1709 referrals for 3055 unique
      patients seen compared with 2388 referrals for 2434 unique patients seen by
      residents. For those patients receiving referral, a mean of 1.72 referrals were
      placed, with residents having significantly more referrals per patient (1.9 +/-
      1.3 vs 1.5 +/- 0.9; P < .0001). For patients at highest risk of utilization,
      residents were referred at a rate of 0.327 compared with 0.226 (P = .0035) in the
      faculty clinic. CONCLUSIONS: In an academic setting, provider and patient factors
      play a role in referral patterns. Residents refer highest-risk patients more
      often than their faculty counterparts, while there is no difference for lower
      risk patients.

PMID- 27870545
TI  - Does Medicare Advantage enrollment affect home healthcare use?
AB  - OBJECTIVES: To compare home health utilization and clinical outcomes between
      Medicare beneficiaries in the fee-for-service (FFS) and Medicare Advantage (MA)
      programs, and to compare regional variation. STUDY DESIGN: We used the 2010 and
      2011 Outcome and Assessment Information Set to identify all home health episodes
      begun in 2010 and to measure 7 clinical home health outcomes that are defined by
      CMS for public reporting. METHODS: We modeled the probability of home health use,
      the duration of home health episodes, and each clinical outcome measure as a
      function of MA versus FFS enrollment and model-specific risk adjustors. Empirical
      Bayes predictions from generalized linear mixed models were aggregated by
      hospital referral region (HRR) to create standardized regional measures of home
      health utilization and mean episode duration. RESULTS: We identified 30,837,130
      FFS and 10,594,658 MA beneficiaries (excluding those dually eligible for
      Medicaid). After adjusting for demographic and clinical patient characteristics,
      the odds of receiving home health among FFS enrollees were 1.83 times those of MA
      (95% CI, 1.82-1.84). Adjusted home health duration was 34% longer for FFS (95%
      CI, 32%-34%). Outcomes differences were small in magnitude and inconsistent
      across measures. Regional variations in use and duration were substantial for
      both FFS and MA enrollees. Within HRRs, correlations between FFS and MA
      utilization rates and between FFS and MA episode durations were 0.51 and 0.94,
      respectively. CONCLUSIONS: MA beneficiaries use less home health than their FFS
      counterparts, but regional factors affect utilization, independent of insurance
      status.

PMID- 27870546
TI  - Integrated care organizations: Medicare financing for care at home.
AB  - OBJECTIVES: As the boomer population ages, there is a growing need for integrated
      care organizations (ICOs) that can integrate both medical care and long-term
      services and supports in the home. This paper presents a policy proposal to
      support the creation of ICOs, redesign care, and provide financing for home- and
      community-based services (HCBS), with the goal of enhancing financial protection
      for beneficiaries, coordinating care, and preventing costly hospital and nursing
      home use. METHODS: This study used the 2012 Medicare Current Beneficiary Survey
      (MCBS) Cost and Use File, inflated to 2016 figures, to describe the
      characteristics of Medicare beneficiaries and their healthcare utilization and
      spending. The costs of covering up to 20 hours of personal care services a week
      were estimated using MCBS population counts, participation assumptions based on
      the literature, and financing design parameters. RESULTS: A targeted HCBS benefit
      could be added to Medicare and financed with income-related cost sharing ranging
      from 5% to 50%, a premium paid by Medicare beneficiaries of approximately $42 a
      month, and payroll taxes estimated at around 0.4% of earnings on employers and
      employees. CONCLUSIONS: Adoption of an HCBS benefit in Medicare would improve
      financial protection for beneficiaries with physical and/or cognitive impairment
      and provide the financing for health organizations to better integrate medical
      and social services. ICOs and delivery models of care emphasizing care at home
      would improve accessibility of care and avoid costly institutionalization;
      additionally, it would also reduce beneficiary reliance on Medicaid.

PMID- 27870547
TI  - Prescribers' perceptions of medication discontinuation: survey instrument
      development and validation.
AB  - OBJECTIVES: Primary care providers (PCPs) and clinical pharmacists have concerns
      about the adverse consequences of using medications inappropriately and generally
      support the notion of reducing unnecessary drugs. Despite this attitude, many
      factors impede clinicians' ability to discontinue medication in clinical
      settings. We sought to develop a survey instrument that assesses PCPs' and
      pharmacists' experiences, attitudes, and beliefs toward medication
      discontinuation. STUDY DESIGN: Survey development and psychometric assessment.
      METHODS: Based on a conceptual framework, we developed a questionnaire and
      surveyed a national sample of Department of Veterans Affairs PCPs with
      prescribing privileges, including physicians, nurse practitioners, physician
      assistants, and clinical pharmacy specialists. We randomly divided respondents
      into derivation and validation samples and used iterations of multi-trait
      analysis to assess the psychometric properties of the proposed measures.
      Multivariable regression models identified factors associated with the outcome of
      self-rated comfort with medication discontinuation. RESULTS: Using established
      criteria for scale development, we identified 5 scales: Medication
      Characteristics, Current Patient Clinical Factors, Predictions of Future Health
      States, Patients' Resources to Manage Their Own Health, and Education and
      Experience. Three of these dimensions predicted providers' self-rated comfort
      with making decisions to discontinue medication (Current Patient Clinical
      Factors, Predictions of Future Health States, and Education and Experience).
      CONCLUSIONS: We developed a psychometrically sound instrument to measure
      prescribers' attitudes toward, and experiences with, medication discontinuation.
      This survey will enable identification of perceived barriers to, and facilitators
      of, proactive discontinuation-an important step toward developing interventions
      that improve the quality and safety of care in medication use.

PMID- 27870548
TI  - Onboard Science Insights and Vehicle Dynamics from Scale-Model Trials of the
      Titan Mare Explorer (TiME) Capsule at Laguna Negra, Chile.
AB  - A scale model of the proposed Titan Mare Explorer capsule was deployed at the
      Planetary Lake Lander field site at Laguna Negra, Chile. The tests served to
      calibrate models of wind-driven drift of the capsule and to understand its
      attitude motion in the wave field, as well as to identify dynamic and acoustic
      signatures of shoreline approach. This information enables formulation of onboard
      trigger criteria for near-shore science data acquisition. Key Words: Titan
      Vehicle dynamics-Science autonomy-Lake. Astrobiology 18, 607-618.

PMID- 27870549
TI  - Evaluation of Bacteriophage Application to Cattle in Lairage at Beef Processing
      Plants to Reduce Escherichia coli O157:H7 Prevalence on Hides and Carcasses.
AB  - Escherichia coli O157:H7 is a major food safety concern for the beef industry.
      Several studies have provided evidence that cattle hides are the main source of
      beef carcass contamination during processing and that reductions in the E. coli
      O157:H7 load on the hides of cattle entering processing facilities will lead to
      reductions in carcass contamination. Bacteriophages have been proposed as a novel
      preharvest antimicrobial intervention to reduce the levels of E. coli O157:H7 on
      cattle hides. The objective of this study was to evaluate a commercialized phage
      application administered in the lairage area of commercial beef processing plants
      for the ability to reduce E. coli O157:H7 contamination of cattle hides and
      carcasses. Cattle lots either received phage spray treatment (n = 289) or did not
      (n = 301), as they entered the lairage environments in two separate experiments
      at two different commercial beef processing plants. Hide and carcass samples were
      collected and analyzed for E. coli O157:H7 prevalence and concentration. Cattle
      hides receiving phage treatment had an E. coli O157:H7 prevalence of 51.8%,
      whereas untreated hides had a prevalence of 57.6%. For carcass samples, the E.
      coli O157 prevalence in treated and untreated samples was 17.1% and 17.6%,
      respectively. The results obtained from these experiments demonstrated that the
      treatment of cattle hides with bacteriophages before processing did not produce a
      significant reduction of E. coli O157:H7 on cattle hides or beef carcasses during
      processing.

PMID- 27870551
TI  - Poor Feeding and Severe Sedation in a Newborn Nursed by a Mother on a Low Dose of
      Amitriptyline.
AB  - Sleep problems are frequently seen during the postpartum period. Some mothers
      need to use sedative agents for insomnia. Amitriptyline is a tricyclic
      antidepressant that has sedative effects. Despite no adverse reports, data on
      safety for the maternal use of this medication on breastfed infants are limited.
      This case report presents severe sedation and poor feeding in the breastfed baby
      of a woman using amitriptyline at 10 mg/day.

PMID- 27870550
TI  - Clinical and Immunological Characteristics of Autoimmune Addison Disease: A
      Nationwide Swedish Multicenter Study.
AB  - Context: Studies of the clinical and immunological features of autoimmune Addison
      disease (AAD) are needed to understand the disease burden and increased
      mortality. Objective: To provide upgraded data on autoimmune comorbidities,
      replacement therapy, autoantibody profiles, and cardiovascular risk factors.
      Design, Setting, and Participants: A cross-sectional, population-based study that
      included 660 AAD patients from the Swedish Addison Registry (2008-2014). When
      analyzing the cardiovascular risk factors, 3594 individuals from the population
      based survey in Northern Sweden, MONICA (monitoring of trends and determinants of
      cardiovascular disease), served as controls. Main Outcome Measures: The endpoints
      were the prevalence of autoimmune comorbidities and cardiovascular risk factors.
      Autoantibodies against 13 autoantigens were determined. Results: The proportion
      of 21-hydroxylase autoantibody-positive patients was 83%, and 62% of patients had
      >=1 associated autoimmune diseases, more frequently coexisting in females (P <
      0.0001). AAD patients had a lower body mass index (P < 0.0001) and prevalence of
      hypertension (P = 0.027) compared with controls. Conventional hydrocortisone
      tablets were used by 89% of the patients, with a mean dose of 28.1 +/- 8.5 mg/d.
      The mean hydrocortisone equivalent dose normalized to the body surface was 14.8
      +/- 4.4 mg/m2/d. A greater hydrocortisone equivalent dose was associated with a
      greater incidence of hypertension (P = 0.046). Conclusions: Careful monitoring of
      AAD patients is warranted to detect associated autoimmune diseases. Contemporary
      Swedish AAD patients did not have an increased prevalence of overweight,
      hypertension, type 2 diabetes mellitus, or hyperlipidemia. However, high
      glucocorticoid replacement doses could be a risk factor for hypertension.

PMID- 27870552
TI  - Glycemic Predictors of Insulin Independence After Total Pancreatectomy With Islet
      Autotransplantation.
AB  - Context: Total pancreatectomy with islet auto transplantation (TPIAT) is a
      treatment for medically refractory chronic pancreatitis that can prevent
      postsurgical diabetes in some patients. Predictors of insulin independence are
      needed for appropriate patient selection and counseling. Objective: To explore
      glycemic predictors of insulin independence after TPIAT. Design: A prospective
      cohort of patients. Methods: We investigated 34 patients undergoing TPIAT from
      2011-2016 at Johns Hopkins Hospital, all had a 75-g oral glucose tolerance test
      (OGTT) administered prior to their TPIAT. The primary outcome was insulin
      independence 1 year after TPIAT. Results: Ten of 34 (29%) patients were insulin
      independent 1 year after TPIAT. All patients with impaired fasting glucose and/or
      impaired glucose tolerance preoperatively were insulin dependent at 1 year. In
      age-adjusted regression analyses, fasting glucose <= 90 mg/dL [odds ratio (OR) =
      6.56; 1.11 to 38.91; P = 0.04], 1-hour OGTT glucose <= 143 mg/dL (OR = 6.65; 1.11
      to 39.91; P = 0.04), and 2-hour OGTT glucose <= 106 mg/dL (OR = 11.74; 1.46 to
      94.14; P = 0.02) were significant predictors of insulin independence. In receiver
      operating characteristic analyses, homeostatic model assessment of beta-cell
      function (HOMA-beta) was the most robust predictor of insulin independence [area
      under the curve (AUC) = 0.88; 0.73 to 1.00]. Conclusions: Normal preoperative
      glucose status and lower fasting and postchallenge OGTT glucose values are
      significant predictors of insulin independence after TPIAT. Higher islet function
      (HOMA-beta) was the strongest predictor. OGTT testing may be a useful tool to aid
      in patient counseling prior to TPIAT and should be further investigated.

PMID- 27870553
TI  - Comparison of Two Intraosseous Devices: The NIO Versus the EZ-IO by Novice Users
      A Randomized Cross Over Trial.
AB  - BACKGROUND: During resuscitation in the field, intraosseous (IO) access may be
      achieved using a variety of available devices, often attempted by inexperienced
      users. AIM: We sought to examine the success rate and ease-of-use ratings of an
      IO device, the NIO(r) (New Intraosseous Persys Medical, Houston, TX, USA) in
      comparison to the Arrow(r) EZ-IO(r) (Teleflex Medical Research Triangle Park, NC,
      USA) by novice users. METHODS: We performed a randomized crossover trial. The
      study model was a porcine hind leg which was cut distally in order to expose the
      marrow. The Study population was composed of pre-graduate medical students
      without prior experience in IO use, all designated future field physicians. The
      students underwent instruction and practiced the use of both devices. After
      practice completion, each student attempted a single IO insertion with both
      devices sequentially in randomized fashion. Success was defined as a flow of
      fluid through the bone marrow after a single IO attempt. Investigators which
      determined the success rate were blinded to the used device. RESULTS: 50 users
      (33 males, 17 females) participated in the trial, mean age of 21.7 years (+/-1).
      NIO users were successful in 92% (46/50) attempts while EZ-IO user success rate
      was 88% (44/50). NIO success rates were comparable to those of EZ-IO (p = NS).
      Results were similar when examining only the initial device used. Median score of
      ease of use was 4 (5 point Likert scale) in both devices (p = NS). 54% (27/50) of
      the participants preferred using the EZ-IO over the NIO (p = NS). CONCLUSION:
      Novice users were equally successful in establishing IO access with the NIO(r) in
      comparison to the EZ-IO(r) in a porcine model.

PMID- 27870554
TI  - Occurrence of Extended-Spectrum beta-Lactamases, Plasmid-Mediated Quinolone
      Resistance, and Disinfectant Resistance Genes in Escherichia coli Isolated from
      Ready-To-Eat Meat Products.
AB  - There are growing concerns about the coselection of resistance against
      antibiotics and disinfectants in bacterial pathogens. The aim of this study was
      to characterize the antimicrobial susceptibility profiles, the prevalence of
      extended-spectrum beta-lactamases (ESBLs), plasmid-mediated quinolone resistance
      genes (PMQRs), and quaternary ammonium compound resistance genes (QACs) in
      Escherichia coli isolated from ready-to-eat (RTE) meat products obtained in
      Guangzhou, China, and to determine whether these genes were colocalized in the
      isolates. A total of 64 E. coli isolates were obtained from 720 RTE meat samples.
      Multidrug resistance was observed in 70.3% of the isolates. A 100% of the
      isolates were resistant to benzalkonium chloride. Four types of beta-lactamase
      genes were identified in the 16 ESBL-producing E. coli isolates: blaSHV (9.4%),
      blaTEM (7.8%), blaCTX-M-15 (1.6%), and blaCTX-M-9 (1.6%). PMQRs were present in
      nine isolates (14.1%), with aac(6')-Ib-cr and qnrD detected in eight (12.5%) and
      one isolate (1.6%), respectively. The QACs ydgE/ydgF were most commonly present
      (60.9%), while qacF, mdfA, sugE(p), emrE, qacG, sugE(c), and qacE were less
      prevalent (1.6%-18.8%). Coexistence of ESBLs and/or PMQRs with QACs was found in
      21 isolates (32.8%). The aac(6')-Ib-cr and blaCTX-M-15 genes were found to be
      cotransferred with qacF in one isolate. The data obtained in this study indicate
      that ESBLs and/or PMQRs with QACs can not only be colocalized but can also be
      cotransferred in E. coli isolates from RTE meat products. The E. coli isolates
      with multiple antimicrobial resistance genes may transmit to humans through food
      chain and thus require further investigation and increased awareness.

PMID- 27870555
TI  - Initiative for standardization of reporting genetics of male infertility.
AB  - The number of publications on research of male infertility is increasing.
      Technologies used in research of male infertility generate complex results and
      various types of data that need to be appropriately managed, arranged, and made
      available to other researchers for further use. In our previous study, we
      collected over 800 candidate loci for male fertility in seven mammalian species.
      However, the continuation of the work towards a comprehensive database of
      candidate genes associated with different types of idiopathic human male
      infertility is challenging due to fragmented information, obtained from a variety
      of technologies and various omics approaches. Results are published in different
      forms and usually need to be excavated from the text, which hinders the gathering
      of information. Standardized reporting of genetic anomalies as well as causative
      and risk factors of male infertility therefore presents an important issue. The
      aim of the study was to collect examples of diverse genomic loci published in
      association with human male infertility and to propose a standardized format for
      reporting genetic causes of male infertility. From the currently available data
      we have selected 75 studies reporting 186 representative genomic loci which have
      been proposed as genetic risk factors for male infertility. Based on collected
      and formatted data, we suggested a first step towards unification of reporting
      the genetics of male infertility in original and review studies. The proposed
      initiative consists of five relevant data types: 1) genetic locus, 2)
      race/ethnicity, number of participants (infertile/controls), 3) methodology, 4)
      phenotype (clinical data, disease ontology, and disease comorbidity), and 5)
      reference. The proposed form for standardized reporting presents a baseline for
      further optimization with additional genetic and clinical information. This data
      standardization initiative will enable faster multi-omics data integration,
      database development and sharing, establishing more targeted hypotheses, and
      facilitating biomarker discovery.

PMID- 27870556
TI  - Twenty Species of Hypobarophilic Bacteria Recovered from Diverse Soils Exhibit
      Growth under Simulated Martian Conditions at 0.7 kPa.
AB  - Bacterial growth at low pressure is a new research area with implications for
      predicting microbial activity in clouds and the bulk atmosphere on Earth and for
      modeling the forward contamination of planetary surfaces like Mars. Here, we
      describe experiments on the recovery and identification of 20 species of
      bacterial hypobarophiles (def., growth under hypobaric conditions of
      approximately 1-2 kPa) in 10 genera capable of growth at 0.7 kPa. Hypobarophilic
      bacteria, but not archaea or fungi, were recovered from diverse soils, and high
      numbers of hypobarophiles were recovered from Arctic and Siberian permafrost
      soils. Isolates were identified through 16S rRNA sequencing to belong to the
      genera Bacillus, Carnobacterium, Clostridium, Cryobacterium, Exiguobacterium,
      Paenibacillus, Rhodococcus, Streptomyces, and Trichococcus. The highest
      population of culturable hypobarophilic bacteria (5.1 * 104 cfu/g) was recovered
      from Colour Lake soils from Axel Heiberg Island in the Canadian Arctic. In
      addition, we extend the number of hypobarophilic species in the genus Serratia to
      six type-strains that include S. ficaria, S. fonticola, S. grimesii, S.
      liquefaciens, S. plymuthica, and S. quinivorans. Microbial growth at 0.7 kPa
      suggests that pressure alone will not be growth-limiting on the martian surface,
      or in Earth's atmosphere up to an altitude of 34 km. Key Words: Barophile
      Extremophilic microorganisms-Habitability-Mars-Special Region. Astrobiology 16,
      964-976.

PMID- 27870557
TI  - Visual cue-specific craving is diminished in stressed smokers.
AB  - BACKGROUND: Craving among smokers is increased by stress and exposure to smoking
      related visual cues. However, few experimental studies have tested both elicitors
      concurrently and considered how exposures may interact to influence craving.
      OBJECTIVE: The current study examined craving in response to stress and visual
      cue exposure, separately and in succession, in order to better understand the
      relationship between craving elicitation and the elicitor. METHOD: Thirty-nine
      smokers (21 males) who forwent smoking for 30 minutes were randomized to complete
      a stress task and a visual cue task in counterbalanced orders (creating the
      experimental groups); for the cue task, counterbalanced blocks of neutral,
      motivational control, and smoking images were presented. Self-reported craving
      was assessed after each block of visual stimuli and stress task, and after a
      recovery period following each task. RESULTS: As expected, the stress and smoking
      images generated greater craving than neutral or motivational control images (p <
      .001). Interactions indicated craving in those who completed the stress task
      first differed from those who completed the visual cues task first (p < .05),
      such that stress task craving was greater than all image type craving (all p's <
      .05) only if the visual cue task was completed first. Conversely, craving was
      stable across image types when the stress task was completed first. CONCLUSIONS:
      Findings indicate when smokers are stressed, visual cues have little additive
      effect on craving, and different types of visual cues elicit comparable craving.
      These findings may imply that once stressed, smokers will crave cigarettes
      comparably notwithstanding whether they are exposed to smoking image cues.

PMID- 27870558
TI  - Antecedent and Concurrent Factors That Influence the Maternal Decision to
      Breastfeed.

PMID- 27870559
TI  - Combinatorial Methods for Epistasis and Dominance.
AB  - We develop computational tools for the analysis of nonlinear genotype-phenotype
      relationships with epistasis among multiple loci or dominance interactions among
      multiple alleles within the same locus. Theory distinguishes between separable
      traits, with removable epistasis, and traits with essential epistasis. Separable
      traits can be transformed to a natural scale where additive methods apply. The
      methods we present solve for the natural scale, exactly when possible and
      approximately when not. Through graph methods, our methods allow for enumeration,
      counting, or sampling of distinct trait architectures satisfying constraints from
      the separability theory. A tool is provided for diagnosing which separability
      constraints are violated by a given nonseparable architecture. For genetic traits
      controlled by limited numbers of loci and alleles, our algorithm enumerates all
      possible trait structures and finds exact or error-minimizing linearizing
      transformations by formulating a constrained optimization program. We find that
      the fraction of possible distinct genetic traits satisfying simple criteria that
      can be fully or approximately linearized is high for small systems and falls as
      the number of alleles or loci increases.

PMID- 27870560
TI  - Effect of Prenatal versus Postnatal Vitamin D Deficiency on Pulmonary Structure
      and Function in Mice.
AB  - Epidemiologic studies have linked gestational vitamin D deficiency to respiratory
      diseases, although mechanisms have not been defined. We hypothesized that
      antenatal vitamin D deficiency would impair airway development and
      alveolarization in a mouse model. We studied the effect of antenatal vitamin D
      deficiency by inducing it in pregnant mice and then compared lung development and
      function in their offspring to littermate controls. Postnatal vitamin D
      deficiency and sufficiency models from each group were also studied. We developed
      a novel tracheal ultrasound imaging technique to measure tracheal diameter in
      vivo. Histological analysis estimated tracheal cartilage total area and
      thickness. We found that vitamin D-deficient pups had reduced tracheal diameter
      with decreased tracheal cartilage minimal width. Vitamin D deficiency increased
      airway resistance and reduced lung compliance, and led to alveolar
      simplification. Postnatal vitamin D supplementation improved lung function and
      radial alveolar count, a parameter of alveolar development, but did not correct
      tracheal narrowing. We conclude that antenatal vitamin D deficiency impairs
      airway and alveolar development and limits lung function. Reduced tracheal
      diameter, cartilage irregularity, and alveolar simplification in vitamin D
      deficient mice may contribute to increased airways resistance and diminished lung
      compliance. Vitamin D supplementation after birth improved lung function and,
      potentially, alveolar simplification, but did not improve defective tracheal
      structure. This mouse model offers insight into the mechanisms of vitamin D
      deficiency-associated lung disease and provides an in vivo model for
      investigating preclinical preventive and therapeutic strategies.

PMID- 27870561
TI  - High-Dose Chemotherapy and Autologous Peripheral-Blood Stem-Cell Transplantation
      for Relapsed Metastatic Germ Cell Tumors: The Indiana University Experience.
AB  - Purpose Patients with relapsed metastatic germ cell tumor (GCT) can be cured with
      second-line and even third-line regimens. We report survival outcomes of patients
      treated with high-dose chemotherapy (HDCT) and peripheral-blood stem-cell
      transplantation (PBSCT) at Indiana University between 2004 and 2014. Patients and
      Methods We conducted a retrospective analysis of 364 consecutive patients with
      GCT who progressed after cisplatin-based combination chemotherapy and were
      subsequently treated with HDCT and PBSCT. Three hundred forty-one patients
      received two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and
      750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT.
      Twenty-three patients received only a single course of HDCT because of
      progressive disease or toxicity. Cox proportional hazards models were used to
      test predictors of disease progression. Results The median age was 32 years
      (range, 17 to 70 years). With a median follow-up of 3.3 years, the 2-year
      progression-free survival (PFS) was 60% (95% CI, 55% to 65%) and the 2-year
      overall survival was 66% (95% CI, 60% to 70%). Three hundred three patients
      received HDCT as second-line therapy with a 2-year PFS of 63% (95% CI, 57% to
      68%), and 61 patients received HDCT as third-line or later therapy with a 2-year
      PFS of 49% (95% CI, 36% to 61%). In a multivariable analysis, factors associated
      with disease progression included use of HDCT as third-line or later therapy,
      platinum-refractory disease, mediastinal primary tumor site, nonseminoma
      histology, intermediate- or poor-risk disease at the time of GCT diagnosis, and
      human chorionic gonadotropin >= 1,000 mIU/mL at initiation of HDCT. There were
      nine treatment-related deaths. Secondary leukemia developed in five patients.
      Conclusion This large single-institution study demonstrates that patients with
      relapsed metastatic GCT are curable by HDCT plus PBSCT even when used in third
      line or later therapy.

PMID- 27870564
TI  - Risk Associated With High-Dose Bicalutamide.

PMID- 27870562
TI  - Monitoring of Serum DNA Methylation as an Early Independent Marker of Response
      and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study.
AB  - Purpose Epigenetic alterations measured in blood may help guide breast cancer
      treatment. The multisite prospective study TBCRC 005 was conducted to examine the
      ability of a novel panel of cell-free DNA methylation markers to predict survival
      outcomes in metastatic breast cancer (MBC) using a new quantitative multiplex
      assay (cMethDNA). Patients and Methods Ten genes were tested in duplicate serum
      samples from 141 women at baseline, at week 4, and at first restaging. A
      cumulative methylation index (CMI) was generated on the basis of six of the 10
      genes tested. Methylation cut points were selected to maximize the log-rank
      statistic, and cross-validation was used to obtain unbiased point estimates.
      Logistic regression or Cox proportional hazard models were used to test
      associations between the CMI and progression-free survival (PFS), overall
      survival (OS), and disease status at first restaging. The added value of the CMI
      in predicting survival outcomes was evaluated and compared with circulating tumor
      cells (CellSearch). Results Median PFS and OS were significantly shorter in women
      with a high CMI (PFS, 2.1 months; OS, 12.3 months) versus a low CMI (PFS, 5.8
      months; OS, 21.7 months). In multivariable models, among women with MBC, a high
      versus low CMI at week 4 was independently associated with worse PFS (hazard
      ratio, 1.79; 95% CI, 1.23 to 2.60; P = .002) and OS (hazard ratio, 1.75; 95% CI,
      1.21 to 2.54; P = .003). An increase in the CMI from baseline to week 4 was
      associated with worse PFS ( P < .001) and progressive disease at first restaging
      ( P < .001). Week 4 CMI was a strong predictor of PFS, even in the presence of
      circulating tumor cells ( P = .004). Conclusion Methylation of this gene panel is
      a strong predictor of survival outcomes in MBC and may have clinical usefulness
      in risk stratification and disease monitoring.

PMID- 27870563
TI  - Economic Burden of Chronic Lymphocytic Leukemia in the Era of Oral Targeted
      Therapies in the United States.
AB  - Purpose Oral targeted therapies represent a significant advance for the treatment
      of patients with chronic lymphocytic leukemia (CLL); however, their high cost has
      raised concerns about affordability and the economic impact on society. Our
      objective was to project the future prevalence and cost burden of CLL in the era
      of oral targeted therapies in the United States. Methods We developed a
      simulation model that evaluated the evolving management of CLL from 2011 to 2025:
      chemoimmunotherapy (CIT) as the standard of care before 2014, oral targeted
      therapies for patients with del(17p) and relapsed CLL from 2014, and for first
      line treatment from 2016 onward. A comparator scenario also was simulated where
      CIT remained the standard of care throughout. Disease progression and survival
      parameters for each therapy were based on published clinical trials. Results The
      number of people living with CLL in the United States is projected to increase
      from 128,000 in 2011 to 199,000 by 2025 (55% increase) due to improved survival;
      meanwhile, the annual cost of CLL management will increase from $0.74 billion to
      $5.13 billion (590% increase). The per-patient lifetime cost of CLL treatment
      will increase from $147,000 to $604,000 (310% increase) as oral targeted
      therapies become the first-line treatment. For patients enrolled in Medicare, the
      corresponding total out-of-pocket cost will increase from $9,200 to $57,000 (520%
      increase). Compared with the CIT scenario, oral targeted therapies resulted in an
      incremental cost-effectiveness ratio of $189,000 per quality-adjusted life-year.
      Conclusion The increased benefit and cost of oral targeted therapies is projected
      to enhance CLL survivorship but can impose a substantial financial burden on both
      patients and payers. More sustainable pricing strategies for targeted therapies
      are needed to avoid financial toxicity to patients.

PMID- 27870566
TI  - Androgen Deprivation Therapy and the Risk of Dementia in Patients With Prostate
      Cancer.
AB  - Purpose Recent observational studies have associated the use of androgen
      deprivation therapy (ADT) with an increased risk of dementia and Alzheimer's
      disease, but these studies had limitations. The objective of this study was to
      determine whether the use of ADT is associated with an increased risk of
      dementia, including Alzheimer's disease, in patients with prostate cancer.
      Patients and Methods Using the United Kingdom's Clinical Practice Research
      Datalink, we assembled a cohort of 30,903 men newly diagnosed with nonmetastatic
      prostate cancer between April 1, 1988 and April 30, 2015, and observed them until
      April 30, 2016. Time-dependent Cox proportional hazards models were used to
      estimate adjusted hazard ratios with 95% CIs of dementia associated with the use
      of ADT compared with nonuse. ADT exposure was lagged by 1 year to account for
      delays associated with the diagnosis of dementia and to minimize reverse
      causality. Secondary analyses assessed whether the risk varied with cumulative
      duration of use and by ADT type. Results During a mean (standard deviation)
      follow-up of 4.3 (3.6) years, 799 patients were newly diagnosed with dementia
      (incidence, 6.0; 95% CI, 5.6 to 6.4) per 1,000 person-years. Compared with
      nonuse, ADT use was not associated with an increased risk of dementia (incidence,
      7.4 v 4.4 per 1,000 person-years, respectively; adjusted hazard ratio, 1.02; 95%
      CI, 0.87 to 1.19). In secondary analyses, cumulative duration of use ( P for
      heterogeneity = .78) and no single type of ADT were associated with an increased
      risk of dementia. Conclusion In this population-based study, the use of ADT was
      not associated with an increased risk of dementia. Additional studies in
      different settings are needed to confirm these findings.

PMID- 27870565
TI  - Concurrent Chemotherapy and Radiation Therapy for Inoperable Locally Advanced Non
      Small-Cell Lung Cancer.
AB  - The Oncology Grand Rounds series is designed to place original reports published
      in the Journal into clinical context. A case presentation is followed by a
      description of diagnostic and management challenges, a review of the relevant
      literature, and a summary of the authors' suggested management approaches. The
      goal of this series is to help readers better understand how to apply the results
      of key studies, including those published in Journal of Clinical Oncology, to
      patients seen in their own clinical practice. A 72-year-old man with a 40-pack
      year tobacco history developed a cough and decreased exercise tolerance. A chest
      x-ray demonstrated a right-upper-lobe opacity. Chest computed tomography (CT)
      scan revealed a 2.5-cm mass in the right upper lobe with multiple mediastinal
      lymph node disease ( Fig 1 ). A positron emission tomography (PET) scan confirmed
      the lung lesion and the mediastinal lymphadenopathy without distant metastases.
      Brain magnetic resonance imaging results were negative. The biopsy specimen
      revealed adenocarcinoma with no actionable mutations present. Cervical
      mediastinoscopy was positive for carcinoma in level 2, 3, 4R, and 7 lymph nodes;
      level 4L was negative. The patient's stage was T1bN2M0, stage IIIA. His medical
      history was significant for hyperlipidemia and hypothyroidism. He had smoked one
      pack a day for 40 years and had quit 15 years earlier. Physical examination was
      unrevealing, and the patient had an Eastern Cooperative Oncology Group
      performance status of 0. Because of the extent of lung cancer in the mediastinum,
      the patient's cancer was deemed inoperable, and he was referred for consideration
      of concurrent chemotherapy and radiation.

PMID- 27870567
TI  - Mindfulness-Based Cognitive Therapy in Advanced Prostate Cancer: A Randomized
      Controlled Trial.
AB  - Purpose Advanced prostate cancer (PC) is associated with substantial psychosocial
      morbidity. We sought to determine whether mindfulness-based cognitive therapy
      (MBCT) reduces distress in men with advanced PC. Methods Men with advanced PC
      (proven metastatic and/or castration-resistant biochemical progression) were
      randomly assigned to an 8-week, group-based MBCT intervention delivered by
      telephone (n = 94) or to minimally enhanced usual care (n = 95). Primary
      intervention outcomes were psychological distress, cancer-specific distress, and
      prostate-specific antigen anxiety. Mindfulness skills were assessed as potential
      mediators of effect. Participants were assessed at baseline and were followed up
      at 3, 6, and 9 months. Main statistical analyses were conducted on the basis of
      intention to treat. Results Fourteen MBCT groups were conducted in the
      intervention arm. Facilitator adherence ratings were high (> 93%). Using random
      effects mixed-regression models, intention-to-treat analyses indicated no
      significant changes in intervention outcomes or in engagement with mindfulness
      for men in MBCT compared with those receiving minimally enhanced usual care. Per
      protocol analyses also found no differences between arms in outcomes or
      engagement, with the exception of the mindfulness skill of observing, which
      increased over time for men in MBCT compared with usual care ( P = .032).
      Conclusion MBCT in this format was not more effective than minimally enhanced
      usual care in reducing distress in men with advanced PC. Future intervention
      research for these men should consider approaches that map more closely to
      masculinity.

PMID- 27870569
TI  - National Cancer Data Base: An Important Research Tool, but Not Population-Based.

PMID- 27870568
TI  - Morbidity and Mortality Differences Between Hematopoietic Cell Transplantation
      Survivors and Other Cancer Survivors.
AB  - Purpose To compare the risks of serious health outcomes among hematopoietic cell
      transplantation (HCT) survivors versus a matched population of patients with
      cancer who did not undergo HCT, where the primary difference may be exposure to
      HCT. Methods Two-year HCT survivors treated at a comprehensive cancer center from
      1992 through 2009 who were Washington State residents (n = 1,792; 52% allogeneic
      and 90% hematologic malignancies) were frequency matched by demographic
      characteristics and underlying cancer diagnosis (as applicable) to non-HCT 2-year
      cancer survivors, using the state cancer registry (n = 5,455) and the general
      population (n = 16,340) using driver's license files. Late outcomes for all three
      cohorts were ascertained from the state hospital discharge and death registries;
      subsequent cancers were ascertained from the state cancer registry. Results After
      median follow-up of 7.1 years, HCT survivors experienced significantly greater
      rates of hospitalization compared with matched non-HCT cancer survivors (280 v
      173 episodes per 1,000 person-years, P < .001) and greater all-cause mortality
      (hazard ratio [HR], 1.1; 95% CI, 1.01 to 1.3). HCT survivors had more
      hospitalizations or death with infections (10-year cumulative incidence, 31% v
      22%; HR, 1.4; 95% CI, 1.3 to 1.6) and respiratory complications (cumulative
      incidence, 27% v 20%; HR, 1.4; 95% CI, 1.2 to 1.5). Risks of digestive, skin, and
      musculoskeletal complications also were greater among HCT versus non-HCT cancer
      survivors. The two groups had similar risks of circulatory complications and
      second cancers. Both HCT and non-HCT cancer survivors had significantly greater
      10-year cumulative incidences of all major organ-system outcomes versus the
      general population. Conclusion History of HCT was associated with late morbidity
      and mortality among cancer survivors. In particular, clinicians who care for HCT
      survivors should be aware of their high rates of late respiratory and infectious
      complications.

PMID- 27870570
TI  - Activating NOTCH1 Mutations Define a Distinct Subgroup of Patients With Adenoid
      Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver
      Metastasis, and Potential Responsiveness to Notch1 Inhibitors.
AB  - Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of
      chemotherapy refractory tumors, with a subset demonstrating an aggressive
      phenotype. We investigated the molecular underpinnings of this phenotype and
      assessed the Notch1 pathway as a potential therapeutic target. Methods We
      genotyped 102 ACCs that had available pathologic and clinical data. Notch1
      activation was assessed by immunohistochemistry for Notch1 intracellular domain.
      Luciferase reporter assays were used to confirm Notch1 target gene expression in
      vitro. The Notch1 inhibitor brontictuzumab was tested in patient-derived
      xenografts from patients with ACC and in a patient with ACC who was enrolled in a
      phase I study. Results NOTCH1 mutations occurred predominantly (14 of 15
      patients) in the negative regulatory region and Pro-Glu-Ser-Thr-rich domains, the
      same two hotspots seen in T-cell acute lymphoblastic leukemias, and led to
      pathway activation in vitro. NOTCH1-mutant tumors demonstrated significantly
      higher levels of Notch1 pathway activation than wild-type tumors on the basis of
      Notch1 intracellular domain staining ( P = .004). NOTCH1 mutations define a
      distinct aggressive ACC subgroup with a significantly higher likelihood of solid
      subtype ( P < .001), advanced-stage disease at diagnosis ( P = .02), higher rate
      of liver and bone metastasis ( P <= .02), shorter relapse-free survival (median,
      13 v 34 months; P = .01), and shorter overall survival (median 30 v 122 months; P
      = .001) when compared with NOTCH1 wild-type tumors. Significant tumor growth
      inhibition with brontictuzumab was observed exclusively in the ACC patient
      derived xenograft model that harbored a NOTCH1 activating mutation. Furthermore,
      an index patient with NOTCH1-mutant ACC had a partial response to brontictuzumab.
      Conclusion NOTCH1 mutations define a distinct disease phenotype characterized by
      solid histology, liver and bone metastasis, poor prognosis, and potential
      responsiveness to Notch1 inhibitors. Clinical studies targeting Notch1 in a
      genotype-defined ACC subgroup are warranted.

PMID- 27870572
TI  - Impact of Extent of Resection on Local Control and Survival in Patients From the
      COG A3973 Study With High-Risk Neuroblastoma.
AB  - Purpose This analysis of patients in the Children's Oncology Group A3973 study
      evaluated the impact of extent of primary tumor resection on local progression
      and survival and assessed concordance between clinical and central imaging review
      based assessments of resection extent. Patients and Methods The analytic cohort
      (n = 220) included patients who had both central surgery review and resection of
      the primary tumor site. For this analysis, resection categories of < 90% and >=
      90% were used, with data on resection extent derived from operating surgeons'
      assessments (all patients), as well as blinded central imaging review of computed
      tomography scans for a subset of 84 patients; assessment results were compared
      for concordance. Treatment outcomes included event-free survival (EFS), overall
      survival (OS), and cumulative incidence of local progression (CILP). Results
      Surgeon-assessed extent of resection was >= 90% in 154 (70%) patients and < 90%
      in 66 (30%). Five-year EFS, OS, and CILP (+/- SE) were 43.5% +/- 3.7%, 54.9% +/-
      3.7%, and 11.9% +/- 2.2%, respectively. EFS was higher with >= 90% resection
      (45.9% +/- 4.3%) than with < 90% resection (37.9% +/- 7.2%; P = .04). Lower CILP
      ( P = .01) was associated with >= 90% resection (8.5% +/- 2.3%) compared with <
      90% resection (19.8% +/- 5.0%). On multivariable analysis, >= 90% resection was
      associated with longer EFS after adjustment for MYCN amplification or diploidy
      but had no significant effect on OS. Concordance between surgeons' assessments of
      resection extent and central image-guided review was low, with agreement of 63%
      (< 90% v >= 90%; simple kappa = -0.0301). Conclusion Despite discordance between
      clinical assessment of resection extent and assessment via central imaging
      review, a surgeon-assessed resection extent >= 90% was associated with
      significantly better EFS and lower CILP. Improving OS, however, remains a
      challenge in this disease. These findings support continued attempts at >= 90%
      resection of the primary tumor in high-risk neuroblastoma.

PMID- 27870573
TI  - Reply to C.G. Drake.

PMID- 27870575
TI  - Reply to D.A. Palma.

PMID- 27870571
TI  - High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute
      Lymphoblastic Leukemia in Adults.
AB  - Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is
      a high-risk subtype of childhood ALL characterized by kinase-activating
      alterations that are amenable to treatment with tyrosine kinase inhibitors. We
      sought to define the prevalence and genomic landscape of Ph-like ALL in adults
      and assess response to conventional chemotherapy. Patients and Methods The
      frequency of Ph-like ALL was assessed by gene expression profiling of 798
      patients with B-cell ALL age 21 to 86 years. Event-free survival and overall
      survival were determined for Ph-like ALL versus non-Ph-like ALL patients.
      Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL.
      Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL,
      including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to
      59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with
      Ph-like ALL had an inferior 5-year event-free survival compared with patients
      with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI,
      42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase
      activating alterations in 88% of patients with Ph-like ALL, including CRLF2
      rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements
      (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations
      (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were
      identified, including four involving new kinase or cytokine receptor genes and
      seven involving new partners for previously identified genes. Conclusion Ph-like
      ALL is a highly prevalent subtype of ALL in adults and is associated with poor
      outcome. The diverse range of kinase-activating alterations in Ph-like ALL has
      important therapeutic implications. Trials comparing the addition of tyrosine
      kinase inhibitors to conventional therapy are required to evaluate the clinical
      utility of these agents in the treatment of Ph-like ALL.

PMID- 27870574
TI  - Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor,
      in Patients With Advanced Solid Tumors Harboring Genetic Alterations in
      Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation
      and Dose-Expansion Study.
AB  - Purpose This two-part, first-in-human study was initiated in patients with
      advanced solid tumors harboring genetic alterations in fibroblast growth factor
      receptors (FGFRs) to determine the maximum tolerated dose (MTD), the recommended
      phase II dose (RP2D), and the schedule, safety, pharmacokinetics,
      pharmacodynamics, and antitumor activity of oral BGJ398, a selective FGFR1-3
      tyrosine kinase inhibitor. Patients and Methods Adult patients were treated with
      escalating dosages of BGJ398 5 to 150 mg once daily or 50 mg twice daily
      continuously in 28-day cycles. During expansion at the MTD, patients with FGFR1
      amplified squamous cell non-small-cell lung cancer (sqNSCLC; arm 1) or other
      solid tumors with FGFR genetic alterations (mutations/amplifications/fusions)
      received BGJ398 daily on a continuous schedule (arm 2), or on a 3-weeks-on/1-week
      off schedule (arm 3). Results Data in 132 patients from the escalation and
      expansion arms are reported (May 15, 2015, cutoff). The MTD, 125 mg daily, was
      determined on the basis of dose-limiting toxicities in four patients (100 mg,
      grade 3 aminotransferase elevations [n = 1]; 125 mg, hyperphosphatemia [n = 1];
      150 mg, grade 1 corneal toxicity [n = 1] and grade 3 aminotransferase elevations
      [n = 1]). Common adverse events in patients treated at the MTD (n = 57) included
      hyperphosphatemia (82.5%), constipation (50.9%), decreased appetite (45.6%), and
      stomatitis (45.6%). A similar safety profile was observed using the 3-weeks-on/1
      week-off schedule (RP2D). However, adverse event-related dose
      adjustments/interruptions were less frequent with the 3-weeks-on/1-week-off
      (50.0%) versus the continuous (73.7%) schedule. Antitumor activity (seven partial
      responses [six confirmed]) was demonstrated with BGJ398 doses >= 100 mg in
      patients with FGFR1-amplified sqNSCLC and FGFR3-mutant bladder/urothelial cancer.
      Conclusion BGJ398 at the MTD/RP2D had a tolerable and manageable safety profile
      and showed antitumor activity in several tumor types, including FGFR1-amplified
      sqNSCLC and FGFR3-mutant bladder/urothelial cancers.

PMID- 27870577
TI  - Cystic Fibrosis in the African Diaspora.
AB  - Identifying mutations that cause cystic fibrosis (CF) is important for making an
      early, unambiguous diagnosis, which, in turn, is linked to better health and a
      greater life expectancy. In patients of African descent, a molecular diagnosis is
      often confounded by the fact that the majority of investigations undertaken to
      identify causative mutations have been conducted on European populations, and CF
      causing mutations tend to be population specific. We undertook a survey of
      published data with the aim of identifying causative CF mutations in patients of
      African descent in the Americas. We found that 1,584 chromosomes had been tested
      in only 6 countries, of which 876 alleles (55.3%) still remained unidentified.
      There were 59 mutations identified. Of those, 41 have been shown to cause CF, 17
      have no associated functional studies, and one (R117H) is of varying clinical
      consequence. The most common mutations identified in the patients of African
      descent were: DeltaF508 (29.4% identified in the United States, Colombia, Brazil,
      and Venezuela); 3120 + 1G>A (8.4% identified in Brazil, the United States, and
      Colombia); G85E (3.8% identified in Brazil); 1811 + 1.6kbA>G (3.7% identified in
      Colombia); and 1342 - 1G>C (3.1% identified in the United States). The majority
      of the mutations identified (81.4%) have been described in just one country. Our
      findings indicate that there is a need to fully characterize the spectrum of CF
      mutations in the diaspora to improve diagnostic accuracy for these patients and
      facilitate treatment.

PMID- 27870576
TI  - Airway Management Strategies for Brain-injured Patients Meeting Standard Criteria
      to Consider Extubation. A Prospective Cohort Study.
AB  - RATIONALE: Patients with acute brain injury are frequently capable of breathing
      spontaneously with minimal ventilatory support despite persistent neurological
      impairment. OBJECTIVES: We sought to describe factors associated with extubation
      timing, success, and primary tracheostomy in these patients. METHODS: We
      conducted a prospective multicenter observational cohort study in three academic
      hospitals in Toronto, Canada. Consecutive brain-injured adults receiving
      mechanical ventilation for at least 24 hours in three intensive care units were
      screened by study personnel daily for extubation consideration criteria. We
      monitored all patients until hospital discharge and used logistic regression
      models to examine associations with extubation failure and delayed extubation.
      MEASUREMENTS AND MAIN RESULTS: Of 192 patients included, 152 (79%) were extubated
      and 40 (21%) received a tracheostomy without an extubation attempt. The rate of
      extubation failure within 72 hours was 32 of 152 (21%), which did not vary
      significantly between those extubated before (early; 6 of 37; 16.2%), within 24
      hours (timely; 14 of 70; 20.0%), or more than 24 hours after meeting criteria to
      consider extubation (delayed; 12 of 45; 26.7%; P = 0.49). Delayed extubation was
      associated with lower a Glasgow Coma Scale (GCS) score at the time of
      consideration of extubation, absence of cough, and new positive sputum cultures.
      Factors independently associated with successful extubation were presence of
      cough (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.42-9.09), fluid
      balance in prior 24 hours (OR, 0.75 per 1-L increase; 95% CI, 0.57-0.98), and age
      (OR, 0.97 per 10-yr increase; 95% CI, 0.95-0.99). A higher GCS score was not
      associated with successful extubation. CONCLUSIONS: Extubation success was
      predicted by younger age, presence of cough, and negative fluid balance, rather
      than GCS score at extubation. These results do not support prolonging intubation
      solely for low GCS score in brain-injured patients.

PMID- 27870578
TI  - Utilizing a Newly Designed Scale for Evaluating Family Support and Its
      Association with Exclusive Breastfeeding.
AB  - BACKGROUND: Although a woman's perception of her family members' support has long
      been established to be an influential factor on exclusive breastfeeding (EBF), it
      still has not been specified and quantified as a facilitator and guidance for
      practice. OBJECTIVE: To investigate in new mothers the association between EBF
      and maternal perception of family support with a standardized scale that
      classified support into nine items of behavioral or psychological support.
      METHOD: A cross-sectional survey was carried out among 655 new mothers to collect
      information on their breastfeeding behavior and their corresponding family
      support at a baby-friendly hospital in Beijing, China. Additionally, a nine-item
      standardized scale was used to explore the perceived family support for
      breastfeeding by new mothers. Breastfeeding behaviors were investigated using the
      indicators recommended by the Multiple Indicator Cluster Surveys. RESULTS: The
      EBF rate was 37.9%. The average score on the family perception scale reported by
      respondents was 28.34 +/- 3.84. The new mothers who performed EBF and who
      predominantly breastfed perceived greater family support (29.55 +/- 3.53; 29.36
      +/- 4.09) compared with those who performed complementary feeding or mixed
      feeding (26.69 +/- 3.33) and those who performed artificial feeding (26.17 +/-
      3.14) (F = 30.296, p < 0.001). A binary logistic regression model was applied,
      and a stepwise regression analysis was performed with these factors; it showed
      that mothers with a positive perception of family support were more likely to
      practice EBF than those with a negative perception (adjusted odds ratio = 3.971;
      95% confidence interval 2.62-6.01; p < 0.001). DISCUSSION: The EBF rate was quite
      low in the population investigated. Family support for breastfeeding could be
      evaluated by a scale, and new mothers' breastfeeding behaviors were strongly
      associated with their perceived family support for breastfeeding. CONCLUSION:
      Community healthcare providers should play a more important role in issues
      regarding breastfeeding among new mothers, and family support should be
      encouraged by health workers.

PMID- 27870579
TI  - Evidence Base Update of Psychosocial Treatments for Child and Adolescent
      Depression.
AB  - Depression in youth is prevalent and disabling and tends to presage a chronic and
      recurrent course of illness and impairment in adulthood. Clinical trial research
      in youth depression has a 30-year history, and evidence-based treatment reviews
      appeared in 1998 and 2008. The current review of 42 randomized controlled trials
      (RCTs) updates these reviews to include RCTs published between 2008 and 2014 (N =
      14) and reevaluates previously reviewed literature. Given the growing maturity of
      the field, this review utilized a stringent set of methodological criteria for
      trial inclusion, most notable for excluding trials based in subclinical samples
      of youth that had been included in previous reviews (N = 12) and including well
      designed RCTs with null and negative findings (N = 8). Findings from the current
      review suggest that evidence for child treatments is notably weaker than for
      adolescent interventions, with no child treatments achieving well-established
      status and the evidentiary basis of treatments downgraded from previous reports.
      Cognitive behavioral therapy (CBT) for clinically depressed children appears to
      be possibly efficacious, with mixed findings across trials. For depressed
      adolescents, both CBT and interpersonal psychotherapy are well-established
      interventions, with evidence of efficacy in multiple trials by independent
      investigative teams. This positive conclusion is tempered by the small size of
      the interpersonal psychotherapy literature (N = 6) and concern that CBT effects
      may be attenuated in clinically complicated samples and when compared against
      active control conditions. Data on predictors, moderators, and mediators are
      examined and priorities for future research discussed.

PMID- 27870580
TI  - Clinical Characterization of Patients With Autosomal Dominant Short Stature due
      to Aggrecan Mutations.
AB  - Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal
      dominant short stature with accelerated skeletal maturation. Objective: We sought
      to characterize the phenotypic spectrum and response to growth-promoting
      therapies. Patients and Methods: One hundred three individuals (57 females, 46
      males) from 20 families with autosomal dominant short stature and heterozygous
      ACAN mutations were identified and confirmed using whole-exome sequencing,
      targeted next-generation sequencing, and/or Sanger sequencing. Clinical
      information was collected from the medical records. Results: Identified ACAN
      variants showed perfect cosegregation with phenotype. Adult individuals had
      mildly disproportionate short stature [median height, -2.8 standard deviation
      score (SDS); range, -5.9 to -0.9] and a history of early growth cessation. The
      condition was frequently associated with early-onset osteoarthritis (12 families)
      and intervertebral disc disease (9 families). No apparent genotype-phenotype
      correlation was found between the type of ACAN mutation and the presence of joint
      complaints. Childhood height was less affected (median height, -2.0 SDS; range, 
      4.2 to -0.6). Most children with ACAN mutations had advanced bone age (bone age -
      chronologic age; median, +1.3 years; range, +0.0 to +3.7 years). Nineteen
      individuals had received growth hormone therapy with some evidence of increased
      growth velocity. Conclusions: Heterozygous ACAN mutations result in a phenotypic
      spectrum ranging from mild and proportionate short stature to a mild skeletal
      dysplasia with disproportionate short stature and brachydactyly. Many affected
      individuals developed early-onset osteoarthritis and degenerative disc disease,
      suggesting dysfunction of the articular cartilage and intervertebral disc
      cartilage. Additional studies are needed to determine the optimal treatment
      strategy for these patients.

PMID- 27870581
TI  - Everolimus in Patients With Advanced Follicular-Derived Thyroid Cancer: Results
      of a Phase II Clinical Trial.
AB  - Background: Mammalian target of rapamycin (mTOR) upregulation has been reported
      to be involved in the pathogenesis of thyroid tumors, and treatment with the mTOR
      inhibitor everolimus has shown promising results in endocrine tumors. We
      conducted a prospective phase II clinical trial to determine the efficacy and
      safety of everolimus in patients with advanced follicular-derived thyroid cancer.
      Patients and Methods: Twenty-eight patients with progressive metastatic or
      locally advanced radioactive refractory differentiated thyroid cancer and 7
      patients with anaplastic thyroid cancer were included and received everolimus 10
      mg orally once daily. The primary endpoint was disease control rate [complete
      (CR) + partial response (PR) + stable disease (SD) > 24 weeks]. Secondary
      endpoints included progression-free survival (PFS), overall survival (OS),
      toxicity, and mutational and pharmacokinetic-related outcomes. Results: Median
      follow-up duration was 38 months (2-64). Seventeen patients (65%) showed SD, of
      which 15 (58%) showed SD >24 weeks. No CR or PR was observed. Median PFS and OS
      were 9 [95% confidence interval (CI): 4 to 14] and 18 (95% CI: 7 to 29) months,
      respectively. Survival was negatively influenced by the presence of bone
      metastases. Toxicity was predominantly grade 1/2 and included anemia (64%), cough
      (64%), stomatitis (61%), and hyperglycemia (61%). Duration of SD was related to
      everolimus exposure. The presence of somatic gene variants related to mTOR
      signaling did not clearly stratify for responses. Conclusion: Everolimus has
      clinically relevant antitumor activity in patients with advanced differentiated
      thyroid cancer. Given the observed disease control rate and the relatively low
      toxicity profile, further investigation of everolimus in sequential or
      combination therapy in these patients is warranted.

PMID- 27870582
TI  - Markers of Islet Endothelial Dysfunction Occur in Male B6.BKS(D)-Leprdb/J Mice
      and May Contribute to Reduced Insulin Release.
AB  - Islet endothelial cells produce paracrine factors that support beta-cell function
      and growth. Endothelial dysfunction underlies diabetic microvascular
      complications; thus, we hypothesized that in diabetes, islet endothelial cells
      become dysfunctional, which may contribute to beta-cell secretory dysfunction.
      Islets/islet endothelial cells were isolated from diabetic B6.BKS(D)-Leprdb/J
      male (db/db) mice, treated with or without the glucose-lowering agent phlorizin,
      or from C57BL/6J mice fed a high-fat diet for 18 weeks and appropriate controls.
      Messenger RNA (mRNA) and/or the protein levels of the cell adhesion molecule E
      selectin (Sele), proinflammatory cytokine interleukin-6 (Il6), vasoconstrictor
      endothelin-1 (Edn1), and endothelial nitric oxide synthase (Nos3; Nos3) were
      evaluated, along with advanced glycation end product immunoreactivity.
      Furthermore, an islet endothelial cell line (MS-1) was exposed to diabetic
      factors (glucose, palmitate, insulin, and tumor necrosis factor-alpha) for six
      days. Conditioned media were collected from these cells, incubated with isolated
      islets, and glucose-stimulated insulin secretion and insulin content were
      assessed. Islet endothelial cells from db/db mice exhibited increased Sele, Il6,
      and Edn1 mRNA levels, decreased Nos3 protein, and accumulation of advanced
      glycation end products. Phlorizin treatment significantly increased Nos3 protein
      levels but did not alter expression of the other markers. High-fat feeding in
      C57BL/6J mice resulted in increased islet Sele, Il6, and Edn1 but no change in
      Nos3. Exposure of islets to conditioned media from MS-1 cells cultured in
      diabetic conditions resulted in a 50% decrease in glucose-stimulated insulin
      secretion and 30% decrease in insulin content. These findings demonstrate that,
      in diabetes, islet endothelial cells show evidence of a dysfunctional phenotype,
      which may contribute to loss of beta-cell function.

PMID- 27870583
TI  - Organic Matter Responses to Radiation under Lunar Conditions.
AB  - Large bodies, such as the Moon, that have remained relatively unaltered for long
      periods of time have the potential to preserve a record of organic chemical
      processes from early in the history of the Solar System. A record of volatiles
      and impactors may be preserved in buried lunar regolith layers that have been
      capped by protective lava flows. Of particular interest is the possible
      preservation of prebiotic organic materials delivered by ejected fragments of
      other bodies, including those originating from the surface of early Earth. Lava
      flow layers would shield the underlying regolith and any carbon-bearing materials
      within them from most of the effects of space weathering, but the encapsulated
      organic materials would still be subject to irradiation before they were buried
      by regolith formation and capped with lava. We have performed a study to simulate
      the effects of solar radiation on a variety of organic materials mixed with lunar
      and meteorite analog substrates. A fluence of ~3 * 1013 protons cm-2 at 4-13 MeV,
      intended to be representative of solar energetic particles, has little detectable
      effect on low-molecular-weight (<=C30) hydrocarbon structures that can be used to
      indicate biological activity (biomarkers) or the high-molecular-weight
      hydrocarbon polymer poly(styrene-co-divinylbenzene), and has little apparent
      effect on a selection of amino acids (<=C9). Inevitably, more lengthy durations
      of exposure to solar energetic particles may have more deleterious effects, and
      rapid burial and encapsulation will always be more favorable to organic
      preservation. Our data indicate that biomarker compounds that may be used to
      infer biological activity on their parent planet can be relatively resistant to
      the effects of radiation and may have a high preservation potential in
      paleoregolith layers on the Moon. Key Words: Radiation-Moon-Regolith-Amino acids
      Biomarkers. Astrobiology 16, 900-912.

PMID- 27870584
TI  - Follow the Carbon: Isotopic Labeling Studies of Early Earth Aerosol.
AB  - Despite the faint young Sun, early Earth might have been kept warm by an
      atmosphere containing the greenhouse gases CH4 and CO2 in mixing ratios higher
      than those found on Earth today. Laboratory and modeling studies suggest that an
      atmosphere containing these trace gases could lead to the formation of organic
      aerosol haze due to UV photochemistry. Chemical mechanisms proposed to explain
      haze formation rely on CH4 as the source of carbon and treat CO2 as a source of
      oxygen only, but this has not previously been verified experimentally. In the
      present work, we use isotopically labeled precursor gases and unit-mass
      resolution (UMR) and high-resolution (HR) aerosol mass spectrometry to examine
      the sources of carbon and oxygen to photochemical aerosol formed in a CH4/CO2/N2
      atmosphere. UMR results suggest that CH4 contributes 70-100% of carbon in the
      aerosol, while HR results constrain the value from 94% to 100%. We also confirm
      that CO2 contributes approximately 10% of the total mass to the aerosol as
      oxygen. These results have implications for the geochemical interpretations of
      inclusions found in Archean rocks on Earth and for the astrobiological potential
      of other planetary atmospheres. Key Words: Atmosphere-Early Earth-Planetary
      atmospheres-Carbon dioxide-Methane. Astrobiology 16, 822-830.

PMID- 27870585
TI  - Another Earth 2.0? Not So Fast.
AB  - The number of confirmed exoplanets now exceeds 3000, with an additional nearly
      5000 exoplanet candidates awaiting confirmation in the NASA Exoplanet Archive (
      2016 ). Nearly weekly we hear about the detection of a new exoplanet similar in
      mass to Earth and located in the so-called habitable zone around its host star.
      The excitement is understandable given our desire to find a second Earth.
      However, the excitement should not lead to an over-interpretation of the
      findings, because the claim can only be to have some crude similarity to Earth
      based on a few selected geophysical parameters. Only a very small fraction of
      these planets will actually be Earth-like. Earth-like would imply multiple
      environmental habitats and presence of a sizable biosphere and complex
      ecosystems, without which Earth, as we experience it, would not exist. Thus, it
      should be clearly communicated to the public that we are probably still many
      years away from having the technological capability to detect an Earth-like
      planet or Earth 2.0 with adequate certainty. Key Words: Habitable zone-Second
      Earth-Habitable planet-Habitability-Life. Astrobiology 16, 817-821.

PMID- 27870586
TI  - Organic Matter Detection on Mars by Pyrolysis-FTIR: An Analysis of Sensitivity
      and Mineral Matrix Effects.
AB  - Returning samples from Mars will require an effective method to assess and select
      the highest-priority geological materials. The ideal instrument for sample triage
      would be simple in operation, limited in its demand for resources, and rich in
      produced diagnostic information. Pyrolysis-Fourier infrared spectroscopy
      (pyrolysis-FTIR) is a potentially attractive triage instrument that considers
      both the past habitability of the sample depositional environment and the
      presence of organic matter that may reflect actual habitation. An important
      consideration for triage protocols is the sensitivity of the instrumental method.
      Experimental data indicate pyrolysis-FTIR sensitivities for organic matter at the
      tens of parts per million level. The mineral matrix in which the organic matter
      is hosted also has an influence on organic detection. To provide an insight into
      matrix effects, we mixed well-characterized organic matter with a variety of dry
      minerals, to represent the various inorganic matrices of Mars samples, prior to
      analysis. During pyrolysis-FTIR, serpentinites analogous to those on Mars
      indicative of the Phyllocian Era led to no negative effects on organic matter
      detection; sulfates analogous to those of the Theiikian Era led, in some
      instances, to the combustion of organic matter; and palagonites, which may
      represent samples from the Siderikian Era, led, in some instances, to the
      chlorination of organic matter. Any negative consequences brought about by these
      mineral effects can be mitigated by the correct choice of thermal extraction
      temperature. Our results offer an improved understanding of how pyrolysis-FTIR
      can perform during sample triage on Mars. Key Words: Mars-Life-detection
      instruments-Search for Mars' organics-Biosignatures. Astrobiology 16, 831-845.

PMID- 27870588
TI  - Assessment of Paramedic Performance on Difficult Airway Simulation.
AB  - OBJECTIVE: Airway management is a common, important intervention for critically
      ill patients in the United States. A key element of prehospital airway management
      is endotracheal intubation (ETI). Prehospital ETI success rates have been shown
      to be as low as 77% compared to in-hospital rates of 95%. Given these rates, the
      use of backup airway devices is a necessary precaution for patient safety. The
      extent to which paramedics integrate backup airway use into their airway
      algorithm is unknown. The purpose of this study was to assess paramedic
      comprehensive airway management practices during a difficult airway simulation
      through which paramedics were obligated to consider alternatives to ETI. METHODS:
      This was an observational study of airway management skills in active paramedics
      (N = 198). A difficult airway simulation was conducted in a mobile simulation
      laboratory; a Type 3 ambulance with four video cameras including an endotracheal
      view to capture airway management. Recordings of paramedic performance were
      assessed using a 110-item checklist covering four key areas: 1) placement of an
      endotracheal tube; 2) application of backup airway following failed ETI; 3)
      ventilation of the patient; and 4) achievement of airway safety and quality
      measures. RESULTS: Paramedics were highly trained with 12 years (IQR: 4-20) of
      advanced life support experience and a median of 40 prehospital intubations over
      their careers (IQR: 15-100). In this difficult airway setting, first pass ETI
      success rate was 55.6%. However, paramedics were challenged with airway
      management following a failed ETI. Only 9% of providers were prepared with a
      clear backup plan. Sixty-three percent of the paramedics successfully placed a
      backup airway within 3 attempts. During the simulation, only 14% properly
      ventilated at a rate of 10-12 breaths/min. Ventilations were maintained without
      interruptions (>30 sec) in 22% of simulations. CONCLUSION: In a difficult airway
      management scenario designed for low ETI success rates, even experienced
      paramedics were challenged with comprehensive airway management. This was
      exemplified by difficulties with the use of backup airway devices. Future work
      needs to be directed at identifying the key determinants for airway management
      success and the development of interventions to improve success with the use of a
      comprehensive airway management plan.

PMID- 27870587
TI  - 17beta-Estradiol Enhances Vascular Endothelial Ets-1/miR-126-3p Expression: The
      Possible Mechanism for Attenuation of Atherosclerosis.
AB  - Context: Endothelial microRNA 126 (miR-126) attenuates the development of
      atherosclerosis (AS). However, there is no evidence showing the role of miR-126
      in estrogen's antiatherogenic effects. Objective: We hypothesized that 17beta
      estradiol (E2) modulates miR-126 expression and thus may improve endothelial
      function and retard AS development. Design/Setting/Participants: This was a
      prospective cohort study of 12 healthy regularly menstruating female volunteers.
      ApoE-/- mice were used as the atherosclerosis model and human umbilical vascular
      endothelial cells (HUVECs) were cultured as the cell model. Main Outcome
      Measures: Serum hormones and miR-126-3p levels were measured up to 3 times for 1
      cycle. Real-time polymerase chain reaction, histology for atherosclerotic
      lesions, immunofluorescence, luciferase assay, transfection experiments, cell
      proliferation, migration and tube formation assay, and western blot were
      performed. Results: Serum concentrations of miR-126-3p in cycling women were
      higher at the ovulatory and luteal phases than in the follicular phase, and they
      were positively correlated with E2 values. Administration of miR-126-3p mimics to
      ApoE-/- mice-attenuated atherogenesis, and antagomir-126-3p partially reversed
      the protective effect of E2 on atherogenesis. In HUVECs, E2 increased miR-126-3p
      expression via upregulation of Ets-1 (a transcription factor for miR-126). c
      Src/Akt signaling was important for E2-mediated expression of Ets-1/miR-126. E2
      decreased expression of miR-126-3p target Spred1 (a protein that inhibits
      mitogenic signaling). Overexpression of Spred1 partially blocked enhancement of
      endothelial cell proliferation, migration, and tube formation by E2.
      Additionally, E2 regulates miR-126-3p-mediated expression of vascular cell
      adhesion molecule-1 to inhibit monocyte adhesion into HUVECs. Conclusions: E2
      protection against atherogenesis is possibly mediated by Ets-1/miR-126.

PMID- 27870589
TI  - Results of a Prospective Study Evaluating a Noninvasive Method of Hemoglobin
      Adjustment for Determining the Diffusing Capacity of the Lung.
AB  - RATIONALE: Measurement of the diffusing capacity of the lung for carbon monoxide
      (DlCO) is significantly influenced by the pulmonary capillary blood volume.
      Consequently, measurements require adjustment for blood hemoglobin concentration
      (DlCOadj) to allow meaningful clinical interpretation. Noninvasive point-of-care
      devices that measure hemoglobin transcutaneously provide immediate values for
      hemoglobin that may be useful in pulmonary function laboratories for determining
      DlCOadj. OBJECTIVES: To test the hypothesis that DlCOadj determinations obtained
      with a commercially available device for noninvasive, point-of-care measurement
      of blood hemoglobin concentrations are not significantly different from
      determinations obtained using hemoglobin concentrations measured conventionally
      in venous blood samples. METHODS: In a prospective open trial, hemoglobin
      measurements were obtained with the Pronto-7 spot check pulse CO-oximeter
      (Massimo, Irvine, CA) and by venipuncture for 205 patients referred for DlCO
      testing at Cincinnati Children's Hospital. Hemoglobin and DlCOadj measurements
      were compared between the two methods, using Student paired t tests and Bland
      Altman plots. To assess variability, the differences in DlCOadj between the two
      methods were also compared by a modification of the current standard for
      acceptable within-session variability for DlCO. Clinical interpretation for
      individual DlCO tests based on DlCOadj values obtained from the two methods were
      compared statistically using Kendall's coefficient of concordance to determine
      whether the Pronto-7 altered the classification of the severity of DlCO defects.
      MEASUREMENTS AND MAIN RESULTS: Measurements of hemoglobin concentration by the
      Pronto-7 analyzer were significantly lower than those obtained from venipuncture
      blood samples (13.1 +/- 1.8 vs. 13.4 +/- 2.0; P = 0.01). However, there were no
      differences for DlCOadj between both methods (23.6 +/- 7.7 vs. 23.7 +/- 7.5
      ml/min/mm Hg; P = 0.42). There was strong correlation between the Pronto-7 and
      venipuncture DlCOadj values (r = 0.99, P < 0.0001). Variability between the two
      methods was low for DlCOadj, with a bias of -0.07. More than 96% of tests met
      acceptable within-session variability. There was no significant difference in the
      clinical interpretation of the DlCO test based on DlCOadj values recovered from
      both methods (Kendall's coefficient, 0.96). CONCLUSIONS: Noninvasive measurement
      of hemoglobin for determination of DlCOadj was accurate and provided acceptable
      within-session variability. The results obtained noninvasively did not alter
      clinical interpretation of test results compared with venipuncture. These
      findings support noninvasive point-of-care devices as an alternative to
      venipuncture for determining hemoglobin to measure DlCOadj in most patients.

PMID- 27870590
TI  - Dry Eye Disease in Patients with Newly Diagnosed Depressive Disorder.
AB  - PURPOSE: Psychiatric conditions and not just the treatments themselves might be
      involved in the pathophysiology of dry eye disease (DED). The aim of our study
      was to evaluate the association between depression and DED using objective and
      subjective tests in patients with newly diagnosed depressive disorder who were
      not using any medication which may help us to determine the sole effect of
      depression on dry eye. METHODS: Thirty-six patients from the psychiatry clinic
      with a new diagnosis of depressive disorder and 32 controls were included in the
      study. All met the Diagnostic and Statistical Manual IV criteria for depression.
      Beck Depression Inventory (BDI) was used to measure depression severity and the
      State-Trait Anxiety Inventory (Stai1, Stai2) for concomitant anxiety symptoms.
      The Ocular Surface Disease Index (OSDI) and Visual Functioning Questionnaires
      (VFQ25) were completed and used to confirm diagnosis of DED in conjunction with
      the tear break up time (TBUT), ocular surface vital dye staining, and Schirmer's
      test. RESULTS: The comparison of depressive and control groups revealed
      significantly lower Schirmer (20.3 +/- 9.9 vs. 25.7 +/- 9.3 mm) and TBUT (7.8 +/-
      5.7 vs. 12.5 +/- 7.8 s) scores with a consistently higher Oxford score (1.8 +/-
      3.2 vs. 0.2 +/- 0.4) in the depressive group. Although the parameters were
      affected in the depressive group, this did not influence OSDI (86.1 +/- 13.6 vs.
      86.6 +/- 13.3) and VFQ25 (30.8 +/- 21.6 vs. 38.5 +/- 29.1) scores. In both
      groups, the three psychological test scores (Stai1-2 and BDI) were correlated to
      each other but none of these tests were correlated to OSDI, VRQL, Schirmer, TBUT,
      and Oxford staining scores. CONCLUSION: Our study shows a definite association
      between depression and DED. We feel that it is important that psychiatrists take
      this into account especially while prescribing antidepressants which may
      aggravate dry eye signs.

PMID- 27870592
TI  - Robot-Assisted Colectomy for Left-Sided Colon Cancer: Comparison of Reduced-Port
      and Conventional Multi-Port Robotic Surgery.
AB  - PURPOSE: The robotic single-port access plus one conventional robotic port, a
      reduced-port robotic surgery (RPRS) for left-sided colon cancer, can enable
      lymphovascular dissection using the wristed instrumentation and safe rectal
      transection through an additional port maintaining the cosmetic advantage of the
      single-port surgery. The aim of this study is to compare the clinicopathological
      outcomes between reduced-port and conventional multi-port robotic colectomy for
      left-sided colon cancer. METHODS: The study group included 23 patients who
      underwent an RPRS and 16 patients who underwent a multi-PRS (MPRS) for left-sided
      colon cancer between August 2013 and January 2016. RESULTS: The operative time
      was significantly shorter in the RPRS group than in the MPRS group (mean time 258
      +/- 67 vs. 319 +/- 66 minutes, P = .009). There were no apparent differences in
      tolerance of diet, postoperative pain score, length of hospital stay, the rate of
      postoperative complications, and the mean number of harvested lymph node, but the
      RPRS group had a significantly smaller total incision length (38 +/- 12 mm vs. 83
      +/- 6 mm, P = .013). CONCLUSIONS: This study shows the feasibility and safety of
      the RPRS, with clinicopathological outcomes that is comparable with that of the
      MPRS for left-sided colon cancer.

PMID- 27870591
TI  - Human transcriptome response to immunization with live-attenuated Venezuelan
      equine encephalitis virus vaccine (TC-83): Analysis of whole blood.
AB  - Venezuelan equine encephalitis virus (VEEV) is an important human and animal
      alphavirus pathogen transmitted by mosquitoes. The virus is endemic in Central
      and South America, but has also caused equine outbreaks in southwestern areas of
      the United States. In an effort to better understand the molecular mechanisms of
      the development of immunity to this important pathogen, we performed
      transcriptional analysis from whole, unfractionated human blood of patients who
      had been immunized with the live-attenuated vaccine strain of VEEV, TC-83. We
      compared changes in the transcriptome between naive individuals who were mock
      vaccinated with saline to responses of individuals who received TC-83.
      Significant transcriptional changes were noted at days 2, 7, and 14 following
      vaccination. The top canonical pathways revealed at early and intermediate time
      points (days 2 and 7) included the involvement of the classic interferon
      response, interferon-response factors, activation of pattern recognition
      receptors, and engagement of the inflammasome. By day 14, the top canonical
      pathways included oxidative phosphorylation, the protein ubiquitination pathway,
      natural killer cell signaling, and B-cell development. Biomarkers were identified
      that differentiate between vaccinees and control subjects, at early,
      intermediate, and late stages of the development of immunity as well as markers
      which were common to all 3 stages following vaccination but distinct from the
      sham-vaccinated control subjects. The study represents a novel examination of
      molecular processes that lead to the development of immunity against VEEV in
      humans and which may be of value as diagnostic targets, to enhance modern vaccine
      design, or molecular correlates of protection.

PMID- 27870593
TI  - Who Cares for Midlife Women?

PMID- 27870594
TI  - Immune Design.

PMID- 27870595
TI  - Human Energy Expenditure and Postural Coordination on the Mechanical Horse.
AB  - The authors investigated and compared the energy expenditure and postural
      coordination of two groups of healthy subjects on a mechanical horse at 4
      increasing oscillation frequencies. Energy expenditure was assessed from the
      oxygen consumption, respiratory quotient, and heart rate values, and postural
      coordination was characterized by relative phase computations between subjects
      (elbow, head, trunk) and horse. The results showed that the postural coordination
      of the riders was better adapted (i.e., maintenance of in-phase and antiphase)
      than that of the nonriders, but the energy expenditure remains the same.
      Likewise, we observed an energy system shifting only for nonriders (from aerobic
      to lactic anaerobic mode). Finally, cross-correlations showed a link between
      energy expenditure and postural coordination in the riders (i.e., effectiveness).

PMID- 27870596
TI  - Improving Breast Cancer Outcomes Through Patient Navigation.

PMID- 27870597
TI  - Exercise Training for Persons with Alzheimer's Disease and Caregivers: A Review
      of Dyadic Exercise Interventions.
AB  - Alzheimer's disease (AD) is the most common form of dementia and the prevalence
      will increase dramatically in the next decades. Although exercise has shown
      benefits for people with dementia due to AD as well as their caregivers, the
      impact of a dyadic exercise intervention including both groups as study
      participants remains to be determined. The authors review the current clinical
      evidence for dyadic exercise interventions, which are exercise regimens applied
      to both the person with dementia and the caregiver. A total of 4 controlled
      trials were reviewed. This review shows that dyadic exercise interventions are
      feasible and may produce a positive effect on functional independence and
      caregiver burden. However, there was insufficient evidence to support a benefit
      of dyadic exercise intervention on cognitive performance and on behavioral and
      neuropsychiatric symptoms in participants with dementia due to AD. A dyadic
      exercise intervention improves functional independence and caregiver burden.
      However, there is a need for well-designed randomized controlled clinical trials
      to confirm these benefits and to investigate several important points such as the
      effects of a dyadic exercise intervention on cognitive and noncognitive outcomes
      of AD, the optimal intensity of exercise training, and the cost effectiveness of
      such a program.

PMID- 27870600
TI  - Laccase Gene Sh-lac Is Involved in the Growth and Melanin Biosynthesis of
      Scleromitrula shiraiana.
AB  - Scleromitrula shiraiana causes the popcorn disease in mulberry trees resulting in
      severe economic losses. Previous studies have shown that melanin may play a vital
      role in establishing the pathogenicity of fungi. In the present study, we
      identified the melanin produced in S. shiraiana belongs to DHN melanin by gas
      chromatography-mass spectrometry, and cloned the laccase Sh-lac, a potential DHN
      melanin biosynthesis gene from S. shiraiana. We obtained two stable Sh-lac
      silenced transformants using RNAi, ilac-4 and 8 to elucidate the DHN melanin
      biosynthetic pathway in S. shiraiana. The melanin production of ilac-4 and ilac-8
      was significantly reduced, and their vegetative growth was also suppressed.
      Results such as these led to a proposal that Sh-lac played a key role in DHN
      melanin formation in S. shiraiana and may function differentially with other
      melanin biosynthetic genes. The inhibition of melanin was accompanied by the
      decrease of oxalic acid and the adhesion of hyphae was impaired. Our results
      indicated that laccase was an important enzyme in the synthesis of melanin and
      might play a critical role in the pathogenicity of S. shiraiana.

PMID- 27870599
TI  - Misfolding leads the way to unraveling signaling pathways in the pathophysiology
      of prion diseases.
AB  - A misfolded version of the prion protein represents an essential component in the
      pathophysiology of fatal neurodegenerative prion diseases, which affect humans
      and animals alike. They may be of sporadic origin, acquired through exogenous
      introduction of infectious misfolded prion protein, or caused by genetic
      alterations in the prion protein coding gene. We have recently described a novel
      pathway linking retention of mutant prion protein in the early secretory pathway
      to activation p38-MAPK and a neurodegenerative phenotype in transgenic mice. Here
      we review the consequences that mutations in prion protein have on intracellular
      transport and stress responses focusing on protein quality control. We also
      discuss the neurotoxic signaling elicited by the accumulation of mutant prion
      protein in the endoplasmic reticulum and the Golgi apparatus. Improved knowledge
      about these processes will help us to better understand complex pathogenesis of
      prion diseases, a prerequisite for therapeutic strategies.

PMID- 27870601
TI  - T Cell Immunity to Varicella-Zoster Virus in the Setting of Advanced HIV and
      Multiple Varicella-Zoster Virus Recurrences.
AB  - A woman presented with at least four manifestations of varicella-zoster virus
      (VZV) infection, including central nervous system vasculitis, during her first 2
      years of HIV infection. We evaluated her CD4 T cell responses to VZV given the
      infrequency with which multiple recurrences of VZV occurred, especially following
      immune reconstitution on antiretroviral therapy.

PMID- 27870598
TI  - Potential applications of nanoparticles in cancer immunotherapy.
AB  - In recent years considerable progress has been made in the field of cancer
      immunotherapy whereby treatments that modulate the body's own immune system are
      used to combat cancer. This has the potential to not only elicit strong anti
      cancer immune responses which can break pre-existing tolerance and help promote
      tumor regression, but could also induce immunological memory which may help
      prevent tumor recurrence. In order to ensure effective delivery of
      immunotherapeutic agents, such as vaccines, checkpoint inhibitors,
      chemotherapeutic agents and nucleic acids, a safe and effective delivery system
      is often required. One such approach is the use of multifunctional nanoparticles
      (NPs), such as liposomes, polymers, micelles, dendrimers, inorganic NPs, and
      hybrid NPs, which have the potential to combine the delivery of a diverse range
      of therapeutic immunomodulators thereby increasing the efficacy of tumor cell
      killing. This review focuses on recent progress in NP-mediated immunotherapy for
      the treatment of cancer.

PMID- 27870602
TI  - Influence of sulfur dioxide-related interactions on PM2.5 formation in iron ore
      sintering.
AB  - : The formation of PM2.5 (aerosol particulate matter less than 2.5 um in
      aerodynamic diameter) in association with SO2 emission during sintering process
      has been studied by dividing the whole sintering process into six typical
      sampling stages. A low-pressure cascade impactor was used to collect PM2.5 by
      automatically segregating particulates into six sizes. It was found that strong
      correlation existed between the emission properties of PM2.5 and SO2. Wet mixture
      layer (overwetted layer and raw mixture layer) had the function to simultaneously
      capture SO2 and PM2.5 during the early sintering stages, and released them back
      into flue gas mainly in the flue gas temperature-rising period. CaSO4 crystals
      constituted the main SO2-related PM2.5 during the disappearing process of
      overwetted layer, which was able to form perfect individual crystals or to form
      particles with complex chemical compositions. Besides the existence of individual
      CaSO4 crystals, mixed crystals of K2SO4-CaSO4 in PM2.5 were also found during the
      first half of the temperature-rising period of flue gas. The interaction between
      fine-grained Ca-based fluxes, potassium vapors, and SO2 was the potential source
      of SO2-related PM2.5. IMPLICATIONS: The emission property of PM2.5 and SO2
      throughout the sintering process exhibited well similarity. This phenomenon
      tightened the relationship between the formation of PM2.5 and the emission of
      SO2. Through revealing the properties of SO2-related PM2.5 during sintering
      process, the potential interaction between fine-grained Ca-based fluxes,
      potassium vapors, and SO2 was found to be the source of SO2-related PM2.5. This
      information can serve as the guidance to develop efficient techniques to control
      the formation and emission of PM2.5 in practical sintering plants.

PMID- 27870603
TI  - Indirect Comparison of Novel Oral Anticoagulants in Women with Nonvalvular Atrial
      Fibrillation.
AB  - BACKGROUND: For nonvalvular atrial fibrillation (NVAF), novel oral anticoagulants
      (NOACs) have been found noninferior to warfarin for stroke/systemic embolization
      prevention, and major bleeding events. Recent meta-analysis of NOACs versus
      warfarin in atrial fibrillation (AF) showed that women on warfarin have greater
      risk of stroke/embolism than men, and when both are treated with NOACs,
      differences disappear. METHODS: NOACs differ in pharmacologic properties, thus
      they may differ from one another in their effects on women with AF. Using dose
      adjusted warfarin as the common comparator, an indirect comparison of
      rivaroxaban, apixaban, dabigatran 110 and 150 mg, and edoxaban 30 and 60 mg for
      efficacy (stroke/embolism prevention) and safety (major bleeding events) in women
      with AF was performed. Data from ROCKET-AF, RE-LY, ENGAGE AF TIMI, and ARISTOTLE
      were analyzed and compared according to the Bucher method. RESULTS: No
      significant difference was found for any NOAC compared with alternatives in
      safety or efficacy for women with AF. Examination of odds ratio comparisons alone
      showed possible favorable efficacy in dabigatran 150 mg, and unfavorable efficacy
      with favorable safety in edoxaban 30 mg. CONCLUSION: NOACs may slightly differ in
      their effect in women; the potential differences are very small and likely
      clinically negligible. Thus, NOACs can be used interchangeably in women according
      to patient and physician preferences to increase adherence.

PMID- 27870604
TI  - Immunoreactivity Analysis of the Nonstructural Proteins of Human Enterovirus 71.
AB  - Human enterovirus 71 (EV-A71) is one of the main etiological agents of hand,
      foot, and mouth disease (HFMD), which has been prevalent mainly in the Asia
      Pacific region in the past several decades. The nonstructural proteins of EV-A71
      will be expressed significantly during viral replication in host cells after EV
      A71 infection. For the determination of the antibodies response against
      nonstructural proteins of EV-A71, in this study, the complete 2ABC, 3ABC, and 3D
      proteins were expressed in Escherichia coli and were then studied for their
      immunoreactivity by immunoblot assay and indirect enzyme-linked immunosorbent
      assay (ELISA), respectively. Three His-tagged fusion proteins were expressed
      effectively in E. coli, which were in agreement with the expected molecular mass.
      The results from immunoblot assay and indirect ELISA showed that all three
      purified fusion proteins can react with IgG antibodies from EV-A71-infected
      patients, but can hardly be recognized by IgG antibodies derived from mice or
      rabbits immunized by inactivated EV-A71 virus particles. The IgG antibody
      response against nonstructural proteins of EV-A71 is associated with viral
      infection or replication, which indicate that these nonstructural proteins could
      be used as candidate antigen for early diagnosis of EV-A71 infection, or to
      distinguish the EV-A71-specific antibodies after viral infection from inactivated
      vaccine immunization.

PMID- 27870605
TI  - Age-Related Differences in Locomotor Strategies During Adaptive Walking.
AB  - Simultaneous control of lower limb stepping movements and trunk motion is
      important for skilled walking; adapting gait to environmental constraints
      requires frequent alternations in stepping and trunk motion. These alterations
      provide a window into the locomotor strategies adopted by the walker. The authors
      examined gait strategies in young and healthy older adults when manipulating step
      width. Anteroposterior (AP) and mediolateral (ML) smoothness (quantified by
      harmonic ratios) and stepping consistency (quantified by gait variability) were
      analyzed during narrow and wide walking while controlling cadence to preferred
      pace. Results indicated older adults preserved ML smoothness at the expense of AP
      smoothness, shortened their steps, and exhibited reduced stepping consistency.
      The authors conclude that older adults prioritized ML control over forward
      progression during adaptive walking challenges.

PMID- 27870606
TI  - The Application of Cortical Arousal Assessment to Control Neuromuscular Fatigue
      During Strength Training.
AB  - The author's aim was to analyze the cortical arousal response during a
      conventional strength training session as a method to assess central nervous
      system fatigue. Sixteen trained men were recruited to perform the maximum number
      of training series composed of 6 exercises of 10 repetition each, at the
      intensity of 70% of the 1 maximum repetition, with a rest period of 2 min between
      exercises and 5 min between series, until exhaustion. Cortical arousal was
      measured using the critical flicker fusion threshold before, after warm-up, after
      each exercises series, after the recovery phase between series, and 15 min and 30
      min after finishing the training session. Participants could not finish the
      fourth series of exercise, corresponding with a significant decrease of cortical
      arousal respect to the warm-up value. The assessment of cortical arousal using
      CFFT during a strength training session could be a fast and efficient method for
      assessing central nervous fatigue. Practically, coaches could modify the training
      protocol according to the individual cortical arousal response in order to
      improve training efficiency and prevent injuries.

PMID- 27870607
TI  - I Don't Want to Die an Old Person.

PMID- 27870609
TI  - Time Series Decomposition into Oscillation Components and Phase Estimation.
AB  - Many time series are naturally considered as a superposition of several
      oscillation components. For example, electroencephalogram (EEG) time series
      include oscillation components such as alpha, beta, and gamma. We propose a
      method for decomposing time series into such oscillation components using state
      space models. Based on the concept of random frequency modulation, gaussian
      linear state-space models for oscillation components are developed. In this
      model, the frequency of an oscillator fluctuates by noise. Time series
      decomposition is accomplished by this model like the Bayesian seasonal adjustment
      method. Since the model parameters are estimated from data by the empirical
      Bayes' method, the amplitudes and the frequencies of oscillation components are
      determined in a data-driven manner. Also, the appropriate number of oscillation
      components is determined with the Akaike information criterion (AIC). In this
      way, the proposed method provides a natural decomposition of the given time
      series into oscillation components. In neuroscience, the phase of neural time
      series plays an important role in neural information processing. The proposed
      method can be used to estimate the phase of each oscillation component and has
      several advantages over a conventional method based on the Hilbert transform.
      Thus, the proposed method enables an investigation of the phase dynamics of time
      series. Numerical results show that the proposed method succeeds in extracting
      intermittent oscillations like ripples and detecting the phase reset phenomena.
      We apply the proposed method to real data from various fields such as astronomy,
      ecology, tidology, and neuroscience.

PMID- 27870608
TI  - Fine particle migration and collection in a wet electrostatic precipitator.
AB  - : Electrostatic precipitation is considered as an effective technology for fine
      particle removal. A lab-scale wet electrostatic precipitator (ESP) with wire-to
      plate configuration was developed to study particle migration and collection. The
      performance of the wet ESP was evaluated in terms of the corona discharge
      characteristics, total removal efficiency and fractional removal efficiency. The
      corona discharge characteristics and particle removal abilities of the wet ESP
      were investigated and compared with dry ESP. Particle removal efficiency was
      influenced by discharge electrode type, SO2 concentration, specific collection
      area (SCA) and particle/droplet interaction. Results showed that the particle
      removal efficiency of wet ESP was elevated to 97.86% from 93.75% of dry ESP.
      Three types of discharge electrodes were investigated. Higher particle removal
      efficiency and larger migration velocity could be obtained with fishbone
      electrode. Particle removal efficiency decreased by 2.87% when SO2 concentration
      increased from 0 ppm to 43 ppm as a result of the suppression of corona discharge
      and particle charging. The removal efficiency increased with higher SCA, but it
      changed by only 0.71% with the SCA increasing from 25.0 m2/(m3/s) to 32.5
      m2/(m3/s). Meanwhile, the increasing of particle and droplet concentration was
      favorable to the particle aggregation and improved particle removal efficiency.
      IMPLICATIONS: This work tends to study the particle migration and collection
      under spraying condition. The performance of a wet electrostatic precipitator
      (ESP) is evaluated in terms of the corona discharge characteristics, total
      particle removal efficiency, and fractional particle removal efficiency. The
      effects of water droplets on particle removal, especially on removal of particles
      with different sizes, is investigated. The optimization work was done to
      determine appropriate water consumption, discharge electrode type, and specific
      collection area, which can provide a basis for wet ESP design and application.

PMID- 27870610
TI  - Neural Circuits Trained with Standard Reinforcement Learning Can Accumulate
      Probabilistic Information during Decision Making.
AB  - Much experimental evidence suggests that during decision making, neural circuits
      accumulate evidence supporting alternative options. A computational model well
      describing this accumulation for choices between two options assumes that the
      brain integrates the log ratios of the likelihoods of the sensory inputs given
      the two options. Several models have been proposed for how neural circuits can
      learn these log-likelihood ratios from experience, but all of these models
      introduced novel and specially dedicated synaptic plasticity rules. Here we show
      that for a certain wide class of tasks, the log-likelihood ratios are
      approximately linearly proportional to the expected rewards for selecting
      actions. Therefore, a simple model based on standard reinforcement learning rules
      is able to estimate the log-likelihood ratios from experience and on each trial
      accumulate the log-likelihood ratios associated with presented stimuli while
      selecting an action. The simulations of the model replicate experimental data on
      both behavior and neural activity in tasks requiring accumulation of
      probabilistic cues. Our results suggest that there is no need for the brain to
      support dedicated plasticity rules, as the standard mechanisms proposed to
      describe reinforcement learning can enable the neural circuits to perform
      efficient probabilistic inference.

PMID- 27870611
TI  - Exponentially Long Orbits in Hopfield Neural Networks.
AB  - We show that Hopfield neural networks with synchronous dynamics and asymmetric
      weights admit stable orbits that form sequences of maximal length. For [Formula:
      see text] units, these sequences have length [Formula: see text]; that is, they
      cover the full state space. We present a mathematical proof that maximal-length
      orbits exist for all [Formula: see text], and we provide a method to construct
      both the sequence and the weight matrix that allow its production. The orbit is
      relatively robust to dynamical noise, and perturbations of the optimal weights
      reveal other periodic orbits that are not maximal but typically still very long.
      We discuss how the resulting dynamics on slow time-scales can be used to generate
      desired output sequences.

PMID- 27870612
TI  - The Population Tracking Model: A Simple, Scalable Statistical Model for Neural
      Population Data.
AB  - Our understanding of neural population coding has been limited by a lack of
      analysis methods to characterize spiking data from large populations. The biggest
      challenge comes from the fact that the number of possible network activity
      patterns scales exponentially with the number of neurons recorded ([Formula: see
      text]). Here we introduce a new statistical method for characterizing neural
      population activity that requires semi-independent fitting of only as many
      parameters as the square of the number of neurons, requiring drastically smaller
      data sets and minimal computation time. The model works by matching the
      population rate (the number of neurons synchronously active) and the probability
      that each individual neuron fires given the population rate. We found that this
      model can accurately fit synthetic data from up to 1000 neurons. We also found
      that the model could rapidly decode visual stimuli from neural population data
      from macaque primary visual cortex about 65 ms after stimulus onset. Finally, we
      used the model to estimate the entropy of neural population activity in
      developing mouse somatosensory cortex and, surprisingly, found that it first
      increases, and then decreases during development. This statistical model opens
      new options for interrogating neural population data and can bolster the use of
      modern large-scale in vivo Ca[Formula: see text] and voltage imaging tools.

PMID- 27870613
TI  - Orientation Histogram-Based Center-Surround Interaction: An Integration Approach
      for Contour Detection.
AB  - Contour is a critical feature for image description and object recognition in
      many computer vision tasks. However, detection of object contour remains a
      challenging problem because of disturbances from texture edges. This letter
      proposes a scheme to handle texture edges by implementing contour integration.
      The proposed scheme integrates structural segments into contours while inhibiting
      texture edges with the help of the orientation histogram-based center-surround
      interaction model. In the model, local edges within surroundings exert a
      modulatory effect on central contour cues based on the co-occurrence statistics
      of local edges described by the divergence of orientation histograms in the local
      region. We evaluate the proposed scheme on two well-known challenging boundary
      detection data sets (RuG and BSDS500). The experiments demonstrate that our
      scheme achieves a high [Formula: see text]-measure of up to 0.74. Results show
      that our scheme achieves integrating accurate contour while eliminating most of
      texture edges, a novel approach to long-range feature analysis.

PMID- 27870614
TI  - Active Inference: A Process Theory.
AB  - This article describes a process theory based on active inference and belief
      propagation. Starting from the premise that all neuronal processing (and action
      selection) can be explained by maximizing Bayesian model evidence-or minimizing
      variational free energy-we ask whether neuronal responses can be described as a
      gradient descent on variational free energy. Using a standard (Markov decision
      process) generative model, we derive the neuronal dynamics implicit in this
      description and reproduce a remarkable range of well-characterized neuronal
      phenomena. These include repetition suppression, mismatch negativity, violation
      responses, place-cell activity, phase precession, theta sequences, theta-gamma
      coupling, evidence accumulation, race-to-bound dynamics, and transfer of dopamine
      responses. Furthermore, the (approximately Bayes' optimal) behavior prescribed by
      these dynamics has a degree of face validity, providing a formal explanation for
      reward seeking, context learning, and epistemic foraging. Technically, the fact
      that a gradient descent appears to be a valid description of neuronal activity
      means that variational free energy is a Lyapunov function for neuronal dynamics,
      which therefore conform to Hamilton's principle of least action.

PMID- 27870615
TI  - Energy Model of Neuron Activation.
AB  - On the basis of the neurophysiological strength-duration (amplitude-duration)
      curve of neuron activation (which relates the threshold amplitude of a
      rectangular current pulse of neuron activation to the pulse duration), as well as
      with the use of activation energy constraint (the threshold curve corresponds to
      the energy threshold of neuron activation by a rectangular current pulse), an
      energy model of neuron activation by a single current pulse has been constructed.
      The constructed model of activation, which determines its spectral properties, is
      a bandpass filter. Under the condition of minimum-phase feature of the neuron
      activation model, on the basis of Hilbert transform, the possibilities of phase
      frequency response calculation from its amplitude-frequency response have been
      considered. Approximation to the amplitude-frequency response by the response of
      the Butterworth filter of the first order, as well as obtaining the pulse
      response corresponding to this approximation, give us the possibility of
      analyzing the efficiency of activating current pulses of various shapes,
      including analysis in accordance with the energy constraint.

PMID- 27870616
TI  - Comparison of Different Generalizations of Clustering Coefficient and Local
      Efficiency for Weighted Undirected Graphs.
AB  - Binary undirected graphs are well established, but when these graphs are
      constructed, often a threshold is applied to a parameter describing the
      connection between two nodes. Therefore, the use of weighted graphs is more
      appropriate. In this work, we focus on weighted undirected graphs. This implies
      that we have to incorporate edge weights in the graph measures, which require
      generalizations of common graph metrics. After reviewing existing generalizations
      of the clustering coefficient and the local efficiency, we proposed new
      generalizations for these graph measures. To be able to compare different
      generalizations, a number of essential and useful properties were defined that
      ideally should be satisfied. We applied the generalizations to two real-world
      networks of different sizes. As a result, we found that not all existing
      generalizations satisfy all essential properties. Furthermore, we determined the
      best generalization for the clustering coefficient and local efficiency based on
      their properties and the performance when applied to two networks. We found that
      the best generalization of the clustering coefficient is [Formula: see text],
      defined in Miyajima and Sakuragawa ( 2014 ), while the best generalization of the
      local efficiency is [Formula: see text], proposed in this letter. Depending on
      the application and the relative importance of sensitivity and robustness to
      noise, other generalizations may be selected on the basis of the properties
      investigated in this letter.

PMID- 27870617
TI  - Analytical Calculation of Mutual Information between Weakly Coupled Poisson
      Spiking Neurons in Models of Dynamically Gated Communication.
AB  - Mutual information is a commonly used measure of communication between neurons,
      but little theory exists describing the relationship between mutual information
      and the parameters of the underlying neuronal interaction. Such a theory could
      help us understand how specific physiological changes affect the capacity of
      neurons to synaptically communicate, and, in particular, they could help us
      characterize the mechanisms by which neuronal dynamics gate the flow of
      information in the brain. Here we study a pair of linear-nonlinear-Poisson
      neurons coupled by a weak synapse. We derive an analytical expression describing
      the mutual information between their spike trains in terms of synapse strength,
      neuronal activation function, the time course of postsynaptic currents, and the
      time course of the background input received by the two neurons. This expression
      allows mutual information calculations that would otherwise be computationally
      intractable. We use this expression to analytically explore the interaction of
      excitation, information transmission, and the convexity of the activation
      function. Then, using this expression to quantify mutual information in
      simulations, we illustrate the information-gating effects of neural oscillations
      and oscillatory coherence, which may either increase or decrease the mutual
      information across the synapse depending on parameters. Finally, we show
      analytically that our results can quantitatively describe the selection of one
      information pathway over another when multiple sending neurons project weakly to
      a single receiving neuron.

PMID- 27870619
TI  - Machine Learning Applied to Alzheimer Disease.

PMID- 27870620
TI  - 2016 RSNA Outstanding Researcher.

PMID- 27870618
TI  - Spinal Injections for Pain Management.
AB  - Image-guided spinal injection is commonly performed in symptomatic patients to
      decrease pain severity, confirm the pain generator, and delay or avoid surgery.
      This article focuses on the radiologist as spine interventionist and addresses
      the following four topics relevant to the radiologist who performs corticosteroid
      injections for pain management: (a) the rationale behind corticosteroid
      injection, (b) the interaction with patients, (c) the role of imaging in
      procedural selection and planning, and (d) the pearls and pitfalls of
      fluoroscopically guided injections. Factors that contribute to the success of a
      pain management service include communication skills and risk mitigation. A
      critical factor is the correlation of clinical symptoms with magnetic resonance
      (MR) imaging findings. Radiologists can leverage their training in MR image
      interpretation to distinguish active pain generators in the spine from incidental
      abnormalities. Knowledge of fluoroscopic anatomy and patterns of contrast
      material flow guide the planning and execution of safe and effective needle
      placement. (c) RSNA, 2016 Online supplemental material is available for this
      article.

PMID- 27870621
TI  - Dynamic Contrast-enhanced MR Imaging of Advanced Hepatocellular Carcinoma:
      Comparison with the Liver Parenchyma and Correlation with the Survival of
      Patients Receiving Systemic Therapy.

PMID- 27870622
TI  - Dual-Energy CT for the Musculoskeletal System.
AB  - The principal advantages of dual-energy computed tomography (CT) over
      conventional CT in the musculoskeletal setting relate to the additional
      information provided regarding tissue composition, artifact reduction, and image
      optimization. This article discusses the manifestations of these in clinical
      practice-urate and bone marrow edema detection, metal artifact reduction, and
      tendon analysis, with potential in arthrography, bone densitometry, and
      metastases surveillance. The basic principles of dual-energy CT physics and
      scanner design will also be discussed. (c) RSNA, 2016.

PMID- 27870623
TI  - No-Touch Multibipolar Radiofrequency Ablation: The New Standard Ablative
      Technique for Hepatocellular Carcinoma 5 cm or Smaller?

PMID- 27870624
TI  - Differentiating between Subsolid and Solid Pulmonary Nodules at CT: What Is Our
      Main Task?

PMID- 27870625
TI  - Ad E. Van Voorthuisen, MD.

PMID- 27870626
TI  - Case 240.

PMID- 27870628
TI  - SUVmax of Pulmonary and Mediastinal Lymph Nodes of Non-Small Cell Lung Cancer
      before and after Dexamethasone.

PMID- 27870629
TI  - Hepatic Gadolinium Deposition in Pediatric Hematopoietic Stem Cell Transplant
      Recipients.

PMID- 27870630
TI  - Case 236: Middle Interhemispheric Variant of Holoprosencephaly.
AB  - History A 13-year-old girl presented for evaluation and further management of
      spastic diplegia cerebral palsy. Absence of the corpus callosum was noted at
      screening prenatal head ultrasonography. She was born at full term via
      spontaneous vaginal delivery. Physical examination revealed decreased axial
      muscle tone and increased muscle tone in her extremities; the latter was more
      severe. She was nonambulatory. No midline craniofacial anomaly was seen. She had
      dysarthria but was able to speak in full sentences. She was in sixth grade with
      an individualized education program. She had mild behavioral problems, such as
      "acting out" in school. Brain magnetic resonance (MR) imaging, including three
      dimensional T1- and T2-weighted sequences, was performed without intravenous
      administration of contrast material to evaluate the brain.

PMID- 27870632
TI  - Benefit-to-Radiation Risk for Breast Screening Tests Is a Flawed Concept.

PMID- 27870633
TI  - DSA of Perimesencephalic Hemorrhage.

PMID- 27870634
TI  - Investigation of and Response to 2 Plague Cases, Yosemite National Park,
      California, USA, 2015.
AB  - In August 2015, plague was diagnosed for 2 persons who had visited Yosemite
      National Park in California, USA. One case was septicemic and the other bubonic.
      Subsequent environmental investigation identified probable locations of exposure
      for each patient and evidence of epizootic plague in other areas of the park.
      Transmission of Yersinia pestis was detected by testing rodent serum, fleas, and
      rodent carcasses. The environmental investigation and whole-genome multilocus
      sequence typing of Y. pestis isolates from the patients and environmental samples
      indicated that the patients had been exposed in different locations and that at
      least 2 distinct strains of Y. pestis were circulating among vector-host
      populations in the area. Public education efforts and insecticide applications in
      select areas to control rodent fleas probably reduced the risk for plague
      transmission to park visitors and staff.

PMID- 27870635
TI  - Alternative exon usage creates novel transcript variants of tumor suppressor
      SHREW-1 gene with differential tissue expression profile.
AB  - Shrew-1, also called AJAP1, is a transmembrane protein associated with E-cadherin
      mediated adherence junctions and a putative tumor suppressor. Apart from its
      interaction with beta-catenin and involvement in E-cadherin internalization,
      little structure or function information exists. Here we explored shrew-1
      expression during postnatal differentiation of mammary gland as a model system.
      Immunohistological analyses with antibodies against either the extracellular or
      the cytoplasmic domains of shrew-1 consistently revealed the expression of full
      length shrew-1 in myoepithelial cells, but only part of it in luminal cells.
      While shrew-1 localization remained unaltered in myoepithelial cells, nuclear
      localization occurred in luminal cells during lactation. Based on these
      observations, we identified two unknown shrew-1 transcript variants encoding N
      terminally truncated proteins. The smallest shrew-1 protein lacks the
      extracellular domain and is most likely the only variant present in luminal
      cells. RNA analyses of human tissues confirmed that the novel transcript variants
      of shrew-1 exist in vivo and exhibit a differential tissue expression profile. We
      conclude that our findings are essential for the understanding and interpretation
      of future functional and interactome analyses of shrew-1 variants.

PMID- 27870636
TI  - MarvelD3 regulates the c-Jun N-terminal kinase pathway during eye development in
      Xenopus.
AB  - Ocular morphogenesis requires several signalling pathways controlling the
      expression of transcription factors and cell-cycle regulators. However, despite a
      well-known mechanism, the dialogue between those signals and factors remains to
      be unveiled. Here, we identify a requirement for MarvelD3, a tight junction
      transmembrane protein, in eye morphogenesis in Xenopus MarvelD3 depletion led to
      an abnormally pigmented eye or even an eye-less phenotype, which was rescued by
      ectopic MarvelD3 expression. Altering MarvelD3 expression led to deregulated
      expression of cell-cycle regulators and transcription factors required for eye
      development. The eye phenotype was rescued by increased c-Jun terminal Kinase
      activation. Thus, MarvelD3 links tight junctions and modulation of the JNK
      pathway to eye morphogenesis.

PMID- 27870637
TI  - Calcium homeostasis alterations in a mouse model of the Dynamin 2-related
      centronuclear myopathy.
AB  - Autosomal dominant centronuclear myopathy (CNM) is a rare congenital myopathy
      characterized by centrally located nuclei in muscle fibers. CNM results from
      mutations in the gene encoding dynamin 2 (DNM2), a large GTPase involved in
      endocytosis, intracellular membrane trafficking, and cytoskeleton regulation. We
      developed a knock-in mouse model expressing the most frequent DNM2-CNM mutation;
      i.e. the KI-Dnm2R465W model. Heterozygous (HTZ) KI-Dnm2 mice progressively
      develop muscle atrophy, impairment of contractile properties, histopathological
      abnormalities, and elevated cytosolic calcium concentration. Here, we aim at
      better characterizing the calcium homeostasis impairment in extensor digitorum
      longus (EDL) and soleus muscles from adult HTZ KI-Dnm2 mice. We demonstrate
      abnormal contractile properties and cytosolic Ca2+ concentration in EDL but not
      soleus muscles showing that calcium impairment is correlated with muscle weakness
      and might be a determinant factor of the spatial muscle involvement. In addition,
      the elevated cytosolic Ca2+ concentration in EDL muscles is associated with an
      increased sarcolemmal permeability to Ca2+ and releasable Ca2+ content from the
      sarcoplasmic reticulum. However, amplitude and kinetics characteristics of the
      calcium transient appear unchanged. This suggests that calcium defect is probably
      not a primary cause of decreased force generation by compromised sarcomere
      shortening but may be involved in long-term deleterious consequences on muscle
      physiology. Our results highlight the first pathomechanism which may explain the
      spatial muscle involvement occurring in DNM2-related CNM and open the way toward
      development of a therapeutic approach to normalize calcium content.

PMID- 27870640
TI  - Gastrointestinal regulatory peptides.

PMID- 27870641
TI  - Growth, metabolism, genetics, and the environment - Alice was not a scientist.

PMID- 27870639
TI  - Molecular pathway activation features of pediatric acute myeloid leukemia (AML)
      and acute lymphoblast leukemia (ALL) cells.
AB  - Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature
      white blood cells in the bone marrow. ALL is most common in the childhood and has
      high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater
      mortality rate than the ALL and is most commonly affecting older adults. However,
      AML is a leading cause of childhood cancer mortality. In this study, we compare
      gene expression and molecular pathway activation patterns in three normal blood,
      seven pediatric ALL and seven pediatric AML bone marrow samples. We identified
      172/94 and 148/31 characteristic gene expression/pathway activation signatures,
      clearly distinguishing pediatric ALL and AML cells, respectively, from the normal
      blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway
      activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found
      132/33 gene expression/pathway AML-specific features, of which only 7/2 were
      common for the adult and pediatric AML and, therefore, age-independent. At the
      pathway level, we found more differences than similarities between the adult and
      pediatric forms. These findings suggest that the adult and pediatric AMLs may
      require different treatment strategies.

PMID- 27870638
TI  - Depressive symptoms are associated with leukocyte telomere length in American
      Indians: findings from the Strong Heart Family Study.
AB  - Patients with depression have an increased risk for many aging-related disorders,
      but the biological mechanisms underlying this link remain to be determined. Here
      we examined the association between depressive symptoms and leukocyte telomere
      length (LTL), a marker of biological aging, among 2,175 American Indians
      participating in the Strong Heart Family Study. Depressive symptoms were assessed
      by the Center for Epidemiologic Studies of Depression Scale (CES-D), which was
      categorized into four levels: none (< 10), mild (10-15), moderate (16 -24), and
      severe (> 24). LTL (T/S ratio) was quantified by qPCR. The association between
      depressive symptoms and LTL was examined by multivariate generalized estimating
      equation models, adjusting for sociodemographic factors, lifestyle factors, and
      chronic conditions. Results showed that individuals with a higher level of
      depressive symptoms had shorter LTL. Specifically, LTL in participants reporting
      none, mild, moderate, and severe depressive symptoms were 1.000, 0.999, 0.988,
      and 0.966, respectively (P for trend = 0.0278). Moreover, gender appears to
      modulate the effect of reported depressive symptoms that fall in the severe range
      (CES-D > 24) on LTL (P for interaction = 0.0346). Our results suggest that
      depressive symptoms may accelerate biological aging through pathways beyond
      traditional risk factors in American Indians.

PMID- 27870642
TI  - Hepatocellular Carcinoma Surveillance Among Patients With Cirrhosis in a
      Population-based Integrated Health Care Delivery System.
AB  - PURPOSE: Fewer than 1 in 5 patients with cirrhosis receive hepatocellular
      carcinoma (HCC) surveillance; however, most studies were performed in select
      patient populations, which may not be informative of practice patterns in
      population-based community practices. Further, few reported guideline-concordant
      consistent surveillance rates. GOALS: Characterize guideline-concordant HCC
      surveillance rates and patient-level factors associated with surveillance among a
      population-based cohort of patients with cirrhosis. STUDY: We retrospectively
      characterized HCC surveillance among cirrhosis patients followed between January
      2010 and December 2012 at an integrated health care delivery system in Washington
      state. Consistent surveillance was defined as an ultrasound every 6 months, and
      inconsistent surveillance was defined as >=1 ultrasound during the 2-year follow
      up period. Univariate and multivariate analyses were conducted to identify
      correlates of HCC surveillance receipt. RESULTS: Of 1137 patients with cirrhosis,
      22 (2%) underwent consistent surveillance, 371 (33%) had inconsistent
      surveillance, and 744 (65%) received no surveillance during follow-up. Correlates
      of HCC surveillance receipt in multivariate analysis included
      Gastroenterology/Hepatology subspecialty care [odds ratio (OR), 1.88; 95%
      confidence interval (CI), 1.44-2.46], Child Pugh B/C cirrhosis (OR, 1.61; 95% CI,
      1.07-2.43), elevated aspartate aminotransferase (OR, 1.63; 95% CI, 1.13-2.35),
      and etiology of liver disease. Compared with hepatitis C-infected patients,
      patients with hepatitis B infection were more likely to undergo surveillance (OR,
      2.72; 95% CI, 1.28-5.81), whereas patients with alcohol-related cirrhosis (OR,
      0.63; 95% CI, 0.42-0.93) and nonalcoholic steatohepatitis (OR, 0.39; 95% CI, 0.28
      0.56) were less likely to undergo surveillance. CONCLUSIONS: Although one third
      of patients undergo inconsistent HCC surveillance, <2% of patients receive
      guideline-concordant biannual HCC surveillance.

PMID- 27870643
TI  - Yellow fever vaccine 17D administered to healthy women aged between 40 and 54
      years halves breast cancer risk: an observational study.
AB  - Transcripts of human endogenous retrovirus K are expressed in most breast cancers
      (BCs). Yellow fever vaccine 17D (YFV) expresses a protein with a closely
      homologous epitope. Cross-reactive immunity could hypothetically inhibit BC
      growth at least in women aged around 50 years at diagnosis, in whom the prognosis
      of BC was found to be better than that in women younger or older. A cohort of 12
      804 women who received YFV in the Veneto Region, Italy, was divided into two
      subcohorts according to age at vaccination and followed up through the Veneto
      Tumor Registry. The time since vaccination until cancer incidence was categorized
      (<=1.9; 2-3.9; 4-5.9; 6-7.9; 8-10.9; >=11 years) and, using the lowest class as a
      reference, the incidence rate ratio for BC with a 95% confidence interval and P
      value was estimated by Poisson regression in each time since vaccination class,
      adjusting for age and calendar period. In 3140 women vaccinated at 40-54 years of
      age, YFV administration resulted in a protective effect of long duration slowly
      fading over time with a U-shaped pattern of response. Overall, BC risk was
      reduced by about 50% (incidence rate ratio=0.46; 95% confidence interval=0.26
      0.83; P=0.009) 2 years after vaccination. Cross-reactive antigens could not be
      the mechanism because no protection was observed in women vaccinated before 40 or
      after 54 years of age. BC cells in a microscopic stage of disease can be
      destroyed or severely damaged by YFV if BC is not very aggressive. To prove that
      treatment is truly effective, a placebo-controlled double-blind trial should be
      conducted.

PMID- 27870644
TI  - Analysis of Physiological Respiratory Variable Alarm Alerts Among Laboring Women
      Receiving Remifentanil.
AB  - BACKGROUND: Remifentanil may be used by laboring women for analgesia, despite
      controversy because of potential apneas. We evaluated candidate variables as
      early warning alerts for apnea, based on prevalence, positive predictive rate,
      sensitivity for apnea event detection, and early warning alert time intervals
      (lead time) for apnea. METHODS: We performed a secondary analysis of respiratory
      physiological data that had been collected during a prospective IRB-approved
      study of laboring women receiving IV patient-controlled boluses of remifentanil
      20 to 60 MUg every 1 to 2 minutes. Analyzed data included the respiratory rate
      (RR), end-tidal CO2 (EtCO2), pulse oximetry (SpO2), heart rate (HR), and the
      Integrated Pulmonary Index (IPI; Capnostream 20; Medtronic, Boulder, CO) that had
      been recorded continuously throughout labor. We defined immediate early warning
      alerts as any drop in a variable value below a prespecified threshold for 15
      seconds: RR < 8 breaths per minute (bpm), EtCO2 < 15 mm Hg, and SpO2 < 92%. We
      defined alerts as "sustained" when the value remained below the threshold for >=
      10 further seconds. The IPI value (1 to 10; 10 = healthy patient, <=4 = immediate
      attention required, 1 = dire condition) was generated from a proprietary
      algorithm using RR, EtCO2, SpO2, and HR parameters. Apnea was defined as maximal
      CO2 < 5 mm Hg for at least 30 consecutive seconds. RESULTS: We counted 62 apneas,
      among 10 of 19 (52.6%) women who received remifentanil (total dose 1725 +/- 1392
      MUg, administered over 160 +/- 132 minutes). We counted 331 immediate early
      warning alerts for the variables; 271 (82%) alerts were sustained for >=10
      seconds. The positive predictive value of alerts for apnea was 35.8% (99%
      confidence interval [CI]: 27.1-45.6), 28.9% (99% CI: 20.8-38.7), 4.3% (99% CI:
      1.9-9.6), and 24.6% (99% CI: 18.3-32.2) for RR, EtCO2, SpO2, and IPI,
      respectively. The sensitivity for apnea event detection was 100% (99% CI: 90.3
      100) for RR (<8 bpm) and IPI (<=4); 75.8% (99% CI: 59.8-86.9) for EtCO2 <15 mm
      Hg; and 14.5% (99% CI: 6.5-29.4) for SpO2 <92%. We found a statistically
      significant difference in the timing of RR, EtCO2, SpO2, and IPI alerts for
      apnea; Friedman's Q = 33.53; P < .0001. The EtCO2 had a median (interquartile
      range) lead time of -0.2 (-12.2 to 0.7) seconds, and SpO2 had a median
      (interquartile range) lead time of 40.0 (40.0 to 40.0) seconds. CONCLUSIONS: The
      majority of women receiving IV remifentanil for labor analgesia experienced
      apneas. Alerts for EtCO2 (<15 mm Hg), RR (<8 bpm), and IPI (<=4) detected most
      apneas, whereas SpO2 alerts missed the majority of apneas. All variables had a
      low positive predictive rate, demonstrating the limitations of the respiratory
      monitors utilized as early warning surveillance for apneas in this setting.

PMID- 27870645
TI  - Where next with preexposure prophylaxis?
AB  - PURPOSE OF REVIEW: Controlling the HIV epidemic remains a major public health
      challenge, and there is an urgent need for novel prevention strategies.
      Preexposure prophylaxis (PrEP) refers to the use of antiretrovirals in HIV
      negative people at high risk to prevent infection and has the potential to be an
      important component in the global effort to end the HIV epidemic by 2030. We
      review the current evidence for the safety and efficacy of PrEP in its different
      forms and address emergent issues and concerns regarding its implementation.
      RECENT FINDINGS: Two further randomized control trials report high efficacy of
      both daily and intermittent PrEP in MSM leading to renewed calls for wider
      availability of PrEP for this group. Oral tenofovir disoproxil/emtricitabine has
      been licensed for PrEP in many countries and is well tolerated, safe and
      effective. SUMMARY: Oral PrEP is well tolerated and effective in reducing the
      incidence of HIV infection in individuals at high risk. Implementation in high
      income countries is progressing slowly; demonstration projects and trials
      continue in low and middle-income countries.

PMID- 27870646
TI  - Ultrasound-Guided Electrodes for Conduction Studies of the Saphenous Nerve.
AB  - PURPOSE: Saphenous nerve conduction studies are difficult, because the nerve is
      hard to localize and evoked responses are small. Ultrasound imaging may assist in
      the accurate localization and optimal positioning of surface (SE) and needle
      electrodes (NE). METHODS: The study population included 39 subjects and was
      divided into two groups. Group A consisted of 20 healthy subjects, whereas group
      B of 19 patients with polyneuropathies. Orthodromic conduction was measured by
      distal supramaximal nerve stimulation. Surface electrode and NE recordings were
      compared. RESULTS: In the control group, SEs recorded responses in 17 of 20
      healthy subjects, whereas NEs in 19. In the patients' group, SEs recorded
      responses in 7 of 19 patients, whereas NEs in 16. In all healthy subjects and
      patients, sensory nerve action potentials recorded by NEs were significantly
      larger than those obtained by SEs (healthy subjects: 5.85 +/- 3.01 MUV vs. 1.98
      +/- 1.37 MUV, P < 0.0001; patients 3.05 +/- 2.35 MUV vs. 0.71 +/- 1.14 MUV, t
      test P < 0.0001). CONCLUSIONS: Ultrasound guidance allows precise electrode
      positioning for saphenous nerve electrophysiological testing. Amplitudes of the
      recorded sensory nerve action potentials are clearly higher with ultrasound
      guided needle than with surface recordings.

PMID- 27870647
TI  - MEG May Reveal Hidden Population of Spikes in Epilepsy With Porencephalic
      Cyst/Encephalomalacia.
AB  - Porencephalic cyst/encephalomalacia is often associated with intractable
      epilepsy. A limited number of studies reported magnetoencephalography's (MEG's)
      potential to help construct treatment strategy for epilepsies associated with
      porencephalic cyst/encephalomalacia. The authors present here simultaneous
      electroencephalography (EEG) and MEG findings in three adult patients with
      pediatric-onset epilepsy due to porencephalic cyst/encephalomalacia. There were
      two types of spikes: one type was detected by MEG only (EEG-/MEG+), and the other
      detected by both EEG and MEG (EEG+/MEG+). Both types were seen in all three
      cases. The EEG-/MEG+ spikes all formed tight clusters; in contrast, the majority
      of EEG+/MEG+ spikes formed loose clusters. These data suggest that MEG may be
      helpful to better identify spike populations in epilepsy patients with
      porencephalic cyst/encephalomalacia. If hidden spike populations were to be found
      by MEG, this information would affect the interpretation of patient's
      pathophysiology and planning of intracranial electrode placement.

PMID- 27870648
TI  - Facilitated temporal summation of pain correlates with clinical pain intensity
      after hip arthroplasty.
AB  - Widespread hyperalgesia has been found in patients with painful hip
      osteoarthritis (OA) which can be normalized after total hip arthroplasty (THA) if
      patients have no residual postoperative pain. This study characterized the
      preoperative somatosensory profiles and provided possible interpretation of
      underlying pain mechanisms that might influence the development of postoperative
      pain. Forty hip OA patients with unilateral pain were assessed before and 6 weeks
      post-THA and compared with 40 asymptomatic control subjects. Hip pain intensity
      at rest and while walking was assessed on a visual analogue scale (VAS).
      Bilateral cuff algometry from the thighs was used to assess the cuff pressure
      pain thresholds, pressure values at VAS scores equal with 6 cm (PVAS6), cuff
      pressure tolerance, and temporal summation of pain (TSP) quantified by an
      increase in VAS scores to repeated phasic cuff stimulations. Correlations between
      hip pain VAS post-THA and preoperative quantitative sensory testing results were
      analyzed. Post-THA hip pain VAS scores decreased (P < 0.05) compared with pre
      THA. The cuff pressure pain threshold, PVAS6, and cuff pressure tolerance were
      significantly lower bilaterally in both patients with pre-THA and post-THA
      compared with controls (P < 0.05). Temporal summation of pain was facilitated
      bilaterally in patients with pre-THA compared with controls and normalized after
      THA in postoperative pain-free patients (P < 0.05). Postoperative hip pain VAS
      scores correlated with preoperative ipsilateral TSP (r = 0.44, P < 0.05).
      Bilateral pressure pain hypersensitivity and facilitated TSP were demonstrated in
      patients with preoperative hip OA. Although persistent postoperative pain is
      known as multifactorial, greater preoperative TSP was associated with greater
      pain and less reduction in pain after THA.

PMID- 27870649
TI  - The Reliability of Disease Activity Score in 28 Joints-C-Reactive Protein Might
      Be Overestimated in a Subgroup of Rheumatoid Arthritis Patients, When the Score
      Is Solely Based on Subjective Parameters: A Cross-sectional, Exploratory Study.
AB  - BACKGROUND: Disease Activity Score in 28 Joints (DAS28) is a scoring system to
      evaluate disease activity and treatment response in rheumatoid arthritis (RA). A
      DAS28 score of greater than 3.2 is a well-described limit for treatment
      intensification; however, the reliability of DAS28 might be overestimated.
      OBJECTIVE: The aim of this study was to evaluate the reliability of DAS28 in RA,
      especially focusing on a subgroup of patients with a DAS28 score of greater than
      3.2. METHODS: Data from RA patients registered in the local part of Danish DANBIO
      Registry were collected in May 2015. Patients were categorized into 2 groups:
      First, those with DAS28 >3.2 with at least one swollen joint (SJ) or elevated C
      reactive protein (CRP) ("objective group"), and second, patients with a DAS28
      >3.2 who had no SJ, and CRP values were within the reference range ("subjective
      group"). Disease Activity Score in 28 Joints, Clinical Disease Activity Index,
      and Health Assessment Questionnaire scores were calculated for each group. We
      defined new score, DAS28 subjective, to focus on subjective parameters. RESULTS:
      Two hundred thirty patients were included; 198 (86.1%) and 32 (13.9%) patients
      were in the objective and subjective groups, respectively. Patients in the
      subjective group had lower mean values of DAS28 (P < 0.001) and Evaluator Global
      Assessment (P < 0.001) with less common immunoglobulin M rheumatoid factor (P <
      0.001) and anti-cyclic citrullinated peptide positivity (P = 0.02) and contrarily
      higher mean values of tender joints (P = 0.04) and DAS28 based on subjective
      parameters (P = 0.003) compared with the objective group. CONCLUSIONS: Rheumatoid
      arthritis scoring systems should be used cautiously in patients who are
      considered for treatment intensification. Patients with central sensitization and
      psychological problems and those with false-positive diagnosis of RA are at high
      risk of overtreatment.

PMID- 27870650
TI  - Surgical Answer to Intralesional Steroid-Induced Skin Atrophy.

PMID- 27870651
TI  - Commentary on Chlorhexidine Keratitis.

PMID- 27870652
TI  - Fatty acid metabolism in macrophages: a target in cardio-metabolic diseases.
AB  - PURPOSE OF REVIEW: Recent studies have highlighted that macrophages dynamically
      and autonomously handle all the facets of fatty acid (FA) metabolism including FA
      oxidation and FA synthesis as well as the synthesis of monounsaturated FAs and
      long chain n-3 and n-6 polyunsaturated FAs. RECENT FINDINGS: Macrophage M2
      polarization is associated with an increase of FA oxidation. However, whether
      increased FA oxidation simply correlates with or is required for M2 polarization
      needs to be further evaluated. Macrophage M1 polarization is associated with the
      activation of FA synthesis, which directly contributes to the inflammatory
      response and affects cholesterol homeostasis and neutral lipid accumulation.
      Finally, recent evidences suggest that macrophages are able to autonomously
      produce signaling monounsaturated FAs, such as palmitoleic acid (C16 : 1 n-7),
      and long chain n-3 and n-6 polyunsaturated FAs, such as arachidonic acid,
      eicosapentaenoic acid, and docosahexaenoic acid. This pathway is regulated by
      liver X receptors and has significant consequences on inflammation and on the FA
      composition of atheroma plaques. SUMMARY: These studies shed new light on the
      tight relationship between FA metabolism, macrophage polarization, and M1/M2
      macrophage functions. These processes may have major consequences for
      atherosclerosis pathogenesis as well as other metabolic disorders.

PMID- 27870653
TI  - Apolipoprotein L1 and apolipoprotein A-IV and their association with kidney
      function.
AB  - PURPOSE OF REVIEW: Chronic kidney disease (CKD) is a common disease with an
      estimated prevalence of 10-12%. There are pronounced differences between
      ethnicities with a 3-fold to 4-fold higher lifetime risk for end-stage kidney
      disease in African Americans compared to European Americans. The purpose of this
      review was to discuss recent findings on two apolipoproteins (apolipoprotein L1
      and A-IV) in the context of kidney disease and kidney function. RECENT FINDINGS:
      The observation that certain apolipoprotein L1 risk genotypes that are only
      present in African Americans might explain a major fraction of the ethnic
      differences for nondiabetic CKD has set the stage for this otherwise under
      researched apolipoprotein. These risk genotypes on the one hand protect African
      Americans against African sleeping sickness but cause on the other hand several
      types of nondiabetic CKD. We are currently beginning to understand the mechanisms
      how apolipoprotein L1 is involved in the modification of lysosomal and
      cytoplasmic membranes. The second protein, apolipoprotein A-IV (apoA-IV), turned
      out to be an early marker of kidney impairment not only in patients with primary
      CKD but also in individuals from the general population. Genetic studies provided
      strong support of a causal effect of kidney function on apoA-IV concentrations.
      SUMMARY: These two apolipoproteins have very distinct properties. Apolipoprotein
      L1 is causally involved in the development of nondiabetic CKD in African
      Americans. In contrast, apoA-IV is an early marker for kidney impairment.

PMID- 27870654
TI  - Dietary fatty acid metabolism in prediabetes.
AB  - PURPOSE OF REVIEW: Experimental evidences are strong for a role of long-chain
      saturated fatty acids in the development of insulin resistance and type 2
      diabetes. Ectopic accretion of triglycerides in lean organs is a characteristic
      of prediabetes and type 2 diabetes and has been linked to end-organ
      complications. The contribution of disordered dietary fatty acid (DFA) metabolism
      to lean organ overexposure and lipotoxicity is still unclear, however. DFA
      metabolism is very complex and very difficult to study in vivo in humans. RECENT
      FINDINGS: We have recently developed a novel imaging method using PET with oral
      administration of 14-R,S-F-fluoro-6-thia-heptadecanoic acid (FTHA) to quantify
      organ-specific DFA partitioning. Our studies thus far confirmed impaired storage
      of DFA per volume of fat mass in abdominal adipose tissues of individuals with
      prediabetes. They also highlighted the increased channeling of DFA toward the
      heart, associated with subclinical reduction in cardiac systolic and diastolic
      function in individuals with prediabetes. SUMMARY: In the present review, we
      summarize previous work on DFA metabolism in healthy and prediabetic states and
      discuss these in the light of our novel findings using PET imaging of DFA
      metabolism. We herein provide an integrated view of abnormal organ-specific DFA
      partitioning in prediabetes in humans.

PMID- 27870655
TI  - Blood pressure treatment levels and choice of antihypertensive agent in people
      with diabetes mellitus: an overview of systematic reviews.
AB  - OBJECTIVE: Multiple systematic reviews address the effect of antihypertensive
      treatment in people with diabetes. Here, we summarize current systematic reviews
      concerning antihypertensive treatment effect at different blood pressure (BP)
      levels, and relative treatment effect of different antihypertensive agents.
      METHODS: We searched MEDLINE, BIOSIS, DARE and CDSR during years 2005-2016.
      Eligibility criteria, number of trials and participants, outcomes analysed,
      statistical methods used for data synthesis, and principal results were extracted
      for each review. Review quality was assessed using the assessment of multiple
      systematic reviews tool. RESULTS: We found four reviews concerning BP treatment
      level. These consistently showed that the effect of antihypertensive treatment on
      mortality, cardiovascular disease and coronary heart disease was attenuated at
      lower BP levels. If SBP was more than 140 mmHg, treatment reduced all-cause and
      cardiovascular mortality, cardiovascular disease, stroke, myocardial infarction
      and heart failure. If SBP was less than 140 mmHg, treatment increased the risk of
      cardiovascular death. We found eight reviews concerning choice of agent. We found
      no difference between angiotensin-converting enzyme inhibitors, angotensin
      receptor blockers, beta-blockers, calcium channel blockers and diuretics in
      preventing all-cause or cardiovascular mortality, combined cardiovascular
      disease, coronary heart disease and end-stage renal disease. Minor differences
      exist for stroke and heart failure. Data were limited on people with type 1
      diabetes and very elderly patients with type 2 diabetes. None of the reviews
      concerning choice of agent included all relevant trials. CONCLUSION: The
      available evidence supports treatment in people with type 2 diabetes and SBP more
      than 140 mmHg, using any of the major antihypertensive drug classes.

PMID- 27870656
TI  - Oscillometric and auscultatory blood pressure measurement methods in children: a
      systematic review and meta-analysis.
AB  - BACKGROUND: The phase-out of mercury from clinical settings calls for valid
      alternatives to assess blood pressure (BP) in children. Aneroid devices provide a
      mercury-free alternative to BP measurements by auscultation, whereas
      oscillometric (automated) devices are increasingly becoming the norm in clinical
      practice due to their ease of use. The aim of this systematic review and meta
      analysis was to investigate the accuracy of oscillometric and aneroid BP devices
      compared with the mercury sphygmomanometer for the measurement of BP in children.
      METHODS: We systematically searched four electronic databases (MEDLINE, Embase,
      CINAHL, and Web of Science) and relevant journals for eligible articles published
      before 30 July 2015. We screened 1415 articles, and two authors independently
      reviewed 92 full-text articles. RESULTS: We included 29 articles (38 studies)
      with 26 879 children. Random-effects model meta-analyses revealed that
      oscillometric devices yield higher measurements of SBP than auscultation with a
      mercury sphygmomanometer (pooled effect estimate 2.53 mmHg; 95% CI 0.57-4.50; P <
      0.05); the pooled effect estimate for SBP was smaller in studies that 'passed'
      validation protocols (1.76 mmHg; 95% CI 0.61-2.81; n = 12). There was no
      significant difference for DBP (pooled effect estimate 1.55 mmHg; 95% CI -0.20 to
      3.31). There was heterogeneity between studies, explained in part by differences
      in manufacturer, study setting and observer training. Only three studies compared
      BP using aneroid and mercury devices and found comparable results. CONCLUSION:
      Oscillometric devices may serve as a suitable alternative to auscultation for
      initial BP screening in the pediatric population.

PMID- 27870657
TI  - Health Care Utilization and Cost in Children and Adolescents With Chronic Pain:
      Analysis of Health Care Claims Data 1 Year Before and After Intensive
      Interdisciplinary Pain Treatment.
AB  - OBJECTIVES: The aim of this study was to analyze changes in health care
      utilization and cost among a sample of highly impaired children and adolescents
      who sought a 3-week intensive interdisciplinary pain treatment (IIPT). MATERIALS
      AND METHODS: Claims data from 7 statutory health insurance companies were
      analyzed for 65 children and adolescents who sought IIPT at the German Paediatric
      Pain Centre. The annual health care utilization and cost were determined for the
      following 4 areas: outpatient care, inpatient care, medications, and remedies and
      aids. We analyzed the changes in resource utilization in the year before (pre_1
      y) IIPT and in the subsequent year (post_1 y). RESULTS: Within the first year
      after IIPT, overall health care costs did not decrease significantly. However,
      the pattern of health care utilization changed. First, significantly more
      children and adolescents started outpatient psychotherapy (P=0.001). Second, the
      number of hospitalized children decreased significantly from 1-year pre to 1-year
      post (P=0.001). Accordingly, there were significantly fewer hospitalizations for
      primary chronic pain disorders at 1-year post (P<0.001). The prescription of
      nonopioids, co-analgesics and opioids was significantly reduced from 1-year pre
      to 1-year post (all P<0.013). DISCUSSION: The present results indicate that the
      health care costs of children and adolescents with severe chronic pain disorders
      do not significantly decrease 1 year after IIPT; however, the treatment becomes
      more goal-focused. Differential diagnosis measures and nonindicated therapeutic
      interventions decreased, and more indicated interventions, such as psychotherapy,
      were used. Future research is needed to investigate the economic long-term
      changes after IIPT.

PMID- 27870658
TI  - Finally, Evidence for Continuation Electroconvulsive Therapy in Major Depressive
      Disorder.

PMID- 27870659
TI  - A novel TWIST1 gene mutation in a patient with Saethre-Chotzen syndrome.

PMID- 27870660
TI  - Patients Negatively Impacted by Discontinuity of Nursing Care During Acute
      Hospitalization.
AB  - BACKGROUND: Continuity of nursing care in hospitals remains poor and not
      prioritized, and we do not know whether discontinuous nursing care is negatively
      impacting patient outcomes. OBJECTIVES: This study aims to examine nursing care
      discontinuity and its effect on patient clinical condition over the course of
      acute hospitalization. RESEARCH DESIGN: Retrospective longitudinal analysis of
      electronic health records (EHR). Average point-in-time discontinuity was
      estimated from time of admission to discharge and compared with theoretical
      predictions for optimal continuity and random nurse assignment. Mixed-effects
      models estimated within-patient change in clinical condition following a
      discontinuity. SUBJECTS: A total of 3892 adult medical-surgical inpatients were
      admitted to a tertiary academic medical center in the Eastern United States
      during July 1, 2011 and December 31, 2011. MEASURES: Exposure: discontinuity of
      nursing care was measured at each nurse assessment entry into a patient's EHR as
      assignment of the patient to a nurse with no prior assignment to that patient.
      OUTCOME: patient's clinical condition score (Rothman Index) continuously tracked
      in the EHR. RESULTS: Discontinuity declined from nearly 100% in the first 24
      hours to 70% at 36 hours, and to 50% by the 10th postadmission day. Discontinuity
      was higher than predicted for optimal continuity, but not random. Each instance
      of discontinuity lead to a 0.12-0.23 point decline in the Rothman Index score,
      with more pronounced effects for older and high-mortality risk patients.
      CONCLUSIONS: Discontinuity in acute care nurse assignments was high and
      negatively impacted patient clinical condition. Improved continuity of provider
      patient assignment should be advocated to improve patient outcomes in acute care.

PMID- 27870661
TI  - Should the Positive Predictive Value be Used to Validate Complications Measures?

PMID- 27870662
TI  - Introducing copayments in the emergency department would deter appropriate visits
      in the Netherlands.
AB  - OBJECTIVE: To determine what the effects of introduction of copayments for self
      referred emergency department (ED) visits would be in the Netherlands and at what
      amount patients would turn to a GP before visiting an ED. METHODS: This
      questionnaire study was carried out in the ED of the Rijnstate Hospital, a
      community teaching hospital in the Netherlands. In the Netherlands, a deductible
      excess system is in use and this study investigated the effects of a copayment
      for self-referred patients (SRPs) on top of the deductible excess. A
      questionnaire was developed and handed out to SRPs. RESULTS: A total of 433 SRPs
      were included; their average age was 33.1 years and 63% were male. With a
      copayment of &OV0556;100, 47% of SRPs would choose to visit their GP instead of
      the ED. A further increase in the copayment amount is largely ineffective in
      reducing the number of self-referred ED visits. The higher the household income
      and education level and the more urgent the triage category, the larger the
      copayment patients are willing to pay. There is no significant relation between
      appropriateness and the amount of copayment that patients are willing to pay and
      we found no specific copayment level that resulted in reducing mainly
      inappropriate ED visits. CONCLUSION: With a copayment of &OV0556;100, 47% of the
      SRPs would choose to visit their GP instead of the ED. There was no specific
      copayment level that resulted in reducing mainly inappropriate ED visits.

PMID- 27870663
TI  - Dendritic cell subset expression in severe chronic rhinosinusitis with nasal
      polyps.
AB  - PURPOSE OF REVIEW: Two main pillars are implicated in nasal polyposis
      development: a severe imbalance in immunomodulation and a mechanical dysfunction
      because of an abnormal remodeling process. Dendritic cells play a crucial role in
      the link between innate and adaptive immune response and orchestrating the T-cell
      response and are implicated in the severe inflammatory process found in nasal
      polypoid tissue. This review summarizes the existent knowledge about dendritic
      cells in nasal polyposis. RECENT FINDINGS: Dendritic cells are found increased in
      nasal polyposis, regardless of subset. Of interest, plasmacytoid dendritic cells
      are decreased in patients with a more severe Th2 profile, suggesting an important
      role of the cytokines milieu in their functional response or that plasmacytoid
      dendritic cell could act mitigating the inflamed process found in polypoid
      tissue. SUMMARY: Understanding the dendritic cell subset expression in different
      environments, as well as the effect of these subsets on T-cell differentiation
      will greatly improve the development of new therapies in nasal polyposis.

PMID- 27870664
TI  - Targeting IL-25 as a novel therapy in chronic rhinosinusitis with nasal polyps.
AB  - PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a
      heterogeneous inflammatory disorder with a poorly understood pathophysiology.
      Recent findings show that epithelial-derived cytokines, including thymic stromal
      lymphopoietin, IL-33, and IL-25, can exacerbate Th2 immune responses, ultimately
      leading to recalcitrant chronic rhinosinusitis and nasal polyps. Although IL-25
      is increased in CRSwNP, the targeting of IL-25 as a therapeutic strategy remains
      largely unexplored. In this review, we outline the many recent advances in our
      understanding of the association between IL-25 and CRSwNP. RECENT FINDINGS:
      Recently, we demonstrated that IL-25, produced primarily by sinonasal epithelial
      cells and infiltrating mast cells, plays an important role in the pathogenesis of
      CRSwNP in Asian patients. Furthermore, IL-25 and IL-25R are elevated in nasal
      polyps. This cytokine has roles in the pathogenesis of CRSwNP via modulating
      group 2 innate lymphoid cells (ILC2s). Similarly, ILC2 enrichment has been
      reported in CRSwNP patients, and a positive correlation has been shown between
      ILC2s and CRSwNP. Clinical trials blocking thymic stromal lymphopoietin and IL-33
      pathways are ongoing using monoclonal antibodies, AMG157 and AMG282, against
      CRSwNP, respectively. SUMMARY: Studies on the role played by IL-25 in the
      pathogenesis of CRSwNP are accumulating and suggest the possibility of a novel
      therapeutic strategy for treating CRSwNP.

PMID- 27870665
TI  - Near-fatal asthma: a heterogeneous clinical entity.
AB  - PURPOSE OF REVIEW: The aims of the present review were to describe the
      heterogeneous nature of near-fatal asthma (NFA) and to summarize the distinctive
      phenotypes identified in this subtype of asthma. RECENT FINDINGS: Clinical,
      physiological, and histological studies have shown a large number of triggers,
      pathological mechanisms, and risk factors associated with NFA. Based on the
      demographic and clinical characteristics of the patients, the circumstances
      surrounding the asthma exacerbation and some distinctive features of the disease,
      several clinical profiles of asthma patients with NFA have been described. Recent
      data show new associations between some gene expression patterns and fatal
      asthma, as well as with some biological markers related to inflammatory or
      immunologic mechanisms in the airways. Also, the use of statistical methods, such
      as cluster analysis, allowed identifying and confirming different phenotypes of
      life-threatening asthma patients. SUMMARY: NFA is a heterogeneous clinical
      entity, in which different patients' clinical profiles may coexist [e.g. rapid
      onset NFA, NFA in patients with dyspnea hypoperception or sensitized to certain
      pneumoallergens (Alternaria alternata, soybean), NFA related to the menstrual
      cycle, brittle asthma]. Knowledge of these phenotypes as well as adequate and
      specific management strategies can reduce morbidity and mortality in patients
      suffering from NFA.

PMID- 27870666
TI  - Introduction: Current State of Healthcare Economics, Expenditures, and Our Moral
      Obligation to Cost Containment.

PMID- 27870667
TI  - The Role of Dedicated Musculoskeletal Urgent Care Centers in Reducing Cost and
      Improving Access to Orthopaedic Care.
AB  - OBJECTIVES: Over the past few years, the United States has seen the rapid growth
      of dedicated musculoskeletal urgent care centers owned and operated by individual
      orthopaedic practices. In June of 2014, our practice opened the first dedicated
      orthopaedic urgent care in the region staffed by physician assistants and
      supervised by orthopaedic surgeons. Our hypothesis is that such centers can
      safely improve orthopaedic care for ambulatory orthopaedic injuries, decrease
      volume for overburdened emergency departments (EDs), reduce wait times and
      significantly decrease the cost of care while improving access to orthopaedic
      specialists. DESIGN: Retrospective review. SETTING: Level 2 trauma center and
      physician-owned orthopaedic urgent care. PATIENTS: Consecutive series of patients
      seen in the hospital ED (n = 87,629) and orthopaedic urgent care (n = 12,722).
      INTERVENTION: None. OUTCOMES: ED wait time, total visit time, time until being
      seen by provider, time until consultation with orthopaedic surgeon, total visit
      charges, and effect on orthopaedic practice revenue. RESULTS: During the 12
      months of study, 12,722 patients were treated in our urgent care. The average
      urgent care wait time until being seen by a provider was 17 minutes compared with
      45 minutes in hospital ED. Total visit time was 43 minutes in the urgent care and
      156 minutes in the hospital ED. Time to being seen by an orthopaedic specialist
      was 1.2 days for urgent care patients compared with 3.4 days for ED patients. The
      average charge for an urgent care visit was $461 compared with $8150 in hospital
      ED. During the course of study, urgent care treatment reduced charges to health
      care system by $97,819,458. Hospital ED orthopaedic volume did decrease as
      expected but total ED patient volume remained the same. There was no measureable
      effect on hospital ED wait times. Hospital surgical case volume did not change
      over the period of study and the orthopaedic census remained stable. Urgent care
      construction, marketing, administration, imaging, and labor costs totaled
      $1,664,445. Urgent care revenue from evaluation and management, imaging, durable
      medical equipment, and casting totaled $2,577,707. Practice revenue from follow
      up care of patients who entered practice through the urgent care totaled
      $7,657,998. CONCLUSION: Dedicated musculoskeletal urgent care clinics operated by
      orthopaedic surgery practices can be extremely beneficial to patients,
      physicians, and the health care system. They clearly improve access to care,
      whereas significantly decreasing overall health care costs for patients with
      ambulatory orthopaedic conditions and injuries. In addition, they can be
      financially beneficial to both patients and orthopaedic surgeons alike without
      cannibalizing local hospital surgical volumes. LEVEL OF EVIDENCE: Therapeutic
      Level III.

PMID- 27870668
TI  - Cost Savings Opportunities in Perioperative Management of the Patients With
      Orthopaedic Trauma.
AB  - Considerable opportunities for cost savings exist surrounding the perioperative
      management of patients with orthopaedic fracture and trauma. Scientific evidence
      is available to support each potential cost savings measure. Much of these data
      had been documented for years but has never been adhered to, resulting in
      millions of dollars in unnecessary testing and treatment. Careful attention to
      preoperative laboratory testing can save huge amounts of money and expedite
      medical clearance for injured patients. The use of a dedicated orthopaedic trauma
      operating room has been shown to improve resource utilization, decrease costs,
      and surgical complications. A variety of anesthetic techniques and agents can
      reduce operative time, recovery room time, and hospital lengths of stay. Strict
      adherence to blood utilization protocols, appropriate deep venous thrombosis
      prophylaxis, and multimodal postoperative pain control with oversight from
      dedicated hip fracture hospitalists is critical to cost containment. Careful
      attention to postoperative disposition to acute care and management of
      postoperative testing and radiographs can also be another area of cost
      containment. Institutional protocols must be created and followed by a team of
      orthopaedic surgeons, hospitalists, and anesthesiologists to significantly impact
      the costs associated with care of patient with orthopaedic trauma and fracture.

PMID- 27870669
TI  - Operating Room Efficiency: Benefits of an Orthopaedic Traumatologist at a Level
      II Trauma Center.
AB  - OBJECTIVES: Fellowship-trained orthopaedic traumatologists are presumably taught
      skill sets leading to "best practice" outcomes and more efficient use of hospital
      resources. This should result in more favorable economic opportunities when
      compared with general orthopaedic surgeons (GOSs) providing similar clinical
      services. The purpose of our study was to compare the operating room utilization
      and financial data of traumatologists versus GOSs at a level II trauma center.
      DESIGN: Retrospective review. SETTING: Level II community-based trauma hospital.
      PATIENTS/PARTICIPANTS: Patients who presented to the emergency room at our
      institution with fractures and orthopaedic conditions requiring surgical
      intervention from January 1, 2010, to December 31, 2011. INTERVENTION: Operative
      fracture fixation by members of our orthopaedic trauma panel, including
      fellowship and nontrauma fellowship-trained orthopaedic surgeons. MAIN OUTCOME
      MEASUREMENTS: Our institutional database was queried to determine operative
      times, surgical supply and implant costs, and surgery labor expenses. Patients
      were stratified according to those treated by our trauma panel's 3
      traumatologists and those treated by the 15 GOSs on our trauma panel. These 2
      groups were then compared using standard statistical methods. RESULTS: A total of
      6449 orthopedic cases were identified and 2076 of these involved fracture care.
      One thousand one hundred ninety-nine patients were treated by traumatologists and
      877 by GOSs. There was no statistical difference detected in American Society of
      Anesthesiologists score between trauma and nontrauma groups. Overall, the
      traumatologist group demonstrated significantly decreased procedure times when
      compared with the GOS group (55.6 vs. 75.8 minutes, P , 0.0001). In 16 of 18 most
      common procedure types, traumatologists were more efficient. This led to
      significantly decreased surgical labor costs ($381.4 vs. $484.8; P < 0.0001) and
      surgical supply and implant costs ($2567 vs. $3003; P < 0.0001). CONCLUSIONS:
      This study demonstrates that in our communitybased trauma system, fracture care
      provided by traumatologists results in improved utilization of hospital-based
      resources when compared with equivalent services provided by GOSs. Significantly
      decreased operative times, surgical labor expenses, and supply and implant costs
      by the fellowship-trained group represent enhanced control of the design, plan,
      execution, and monitoring of orthopaedic trauma care. Traumatologists can provide
      leadership recommendations for operating room efficiency in community-based
      orthopaedic trauma care models. LEVEL OF EVIDENCE: Economic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 27870670
TI  - Operating Room Supply Costs in Orthopaedic Trauma: Cost Containment
      Opportunities.
AB  - In the current health care environment, cost containment is more important than
      ever. Most physicians currently are unaware of the cost of operating room
      supplies. A large amount of waste occurs secondary to lack of knowledge and
      absence of physician incentives for cost saving. Many of the decisions for supply
      use can be based on good scientific evidence, which supports specific cost saving
      measures. Careful attention to blood utilization and use of tranexamic acid has
      the potential to save millions in the hip fracture treatment and arthroplasty
      treatments. Standardization of surgical preparation and draping can decrease
      costs and prevent costly surgical site infections. Following protocols and
      guidelines for bone graft and orthobiologics is critical. The clinical and legal
      repercussions of retained instruments and costs associated with dropped implants
      is a huge source of wasted health care dollars. Reprocessing programs for
      external fixators and tourniquets have been extremely successful. A myriad of
      opportunities for intraoperative cost savings exist that could be applied to
      nearly every orthopaedic surgery performed in the United States. It is incumbent
      on all surgeons to put aside the choices made out of habit and take part in
      reducing operating room waste for the benefit of hospitals, patients, and the
      health care system. When applied to the 5.3 million orthopaedic surgeries
      performed annually in the United States, billions of dollars could easily be
      saved with no adverse effect on patient care.

PMID- 27870671
TI  - Surgeon Attitudes Regarding the Use of Generic Implants: An OTA Survey Study.
AB  - OBJECTIVES: To determine the role of generic orthopaedic trauma implants in the
      current orthopaedic trauma market, as perceived by OTA members, and investigate
      potential hurdles to the use of generic implants and other cost-containment
      measures. DESIGN: Survey study. SETTING: Not applicable. PARTICIPANTS: All active
      OTA members with valid e-mail addresses were invited to participate.
      INTERVENTION: Participants completed a brief online survey with questions
      regarding participation in cost-containment and incentive programs, industry
      relationships, generic implant use, and the role of surgeons in cost containment.
      MAIN OUTCOME MEASURES: Survey data. RESULTS: Participation in cost-containment
      programs (comanagement agreements, bundled payment for care improvement, and
      gainsharing) was found to be very low among participants (17%, 36.5%, 17%,
      respectively). Industry sales representatives were present in a majority of
      participants' cases (76.9%) the majority of time, but relatively a few surgeons
      (21.2%) felt their presence was necessary. Most surgeons were aware of the
      availability of generic implants (72.6%), but a few had adopted the use of such
      implants (25.5%), despite 50/52 (96.2%) prescribing generic drugs and 45/52
      (86.5%) using generic products in their own households. CONCLUSIONS: Most
      participants agreed that generic orthopaedic implants have a role in cost
      containment, but a few have adopted these implants. The presence of sales
      representatives does not seem to be necessary for most surgeons, and minimizing
      or eliminating their presence may result in substantial savings for health care
      institutions. Increased education and the use of financial incentive programs may
      encourage improved surgeon participation in cost containment and adoption of
      generic implants and may help reduce health care spending. LEVEL OF EVIDENCE:
      Level 4. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 27870672
TI  - The Clinical and Economic Impact of Generic Locking Plate Utilization at a Level
      II Trauma Center.
AB  - OBJECTIVES: In today's climate of cost containment and fiscal responsibility,
      generic implant alternatives represent an interesting area of untapped resources.
      As patents have expired on many commonly used trauma implants, generic
      alternatives have recently become available from a variety of sources. The
      purpose of this study was to examine the clinical and economic impact of a cost
      containment program using high quality, generic orthopaedic locking plates. The
      implants available for study were anatomically precontoured plates for the
      clavicle, proximal humerus, distal radius, proximal tibia, distal tibia, and
      distal fibula. DESIGN: Retrospective review. SETTING: Level II Trauma center.
      PATIENTS: 828 adult patients with operatively managed clavicle, proximal humerus,
      distal radius, proximal tibia, tibial pilon, and ankle fractures. INTERVENTION:
      Operative treatment with conventional or generic implants. RESULTS: The 414
      patients treated with generic implants were compared with 414 patients treated
      with conventional implants. There were no significant differences in age, sex,
      presence of diabetes, smoking history or fracture type between the generic and
      conventional groups. No difference in operative time, estimated blood loss or
      intraoperative complication rate was observed. No increase in postoperative
      infection rate, hardware failure, hardware loosening, malunion, nonunion or need
      for hardware removal was noted. Overall, our hospital realized a 56% reduction in
      implant costs, an average savings of $1197 per case, and a total savings of
      $458,080 for the study period. CONCLUSIONS: Use of generic orthopaedic implants
      has been successful at our institution, providing equivalent clinical outcomes
      while significantly reducing implant expenditures. Based on our data, the use of
      generic implants has the potential to markedly reduce operative costs as long as
      quality products are used. LEVEL OF EVIDENCE: Therapeutic Level III.

PMID- 27870673
TI  - Financial Impact of Dual Vendor, Matrix Pricing, and Sole-Source Contracting on
      Implant Costs.
AB  - Implant costs comprise the largest proportion of operating room supply costs for
      orthopedic trauma care. Over the years, hospitals have devised several methods of
      controlling these costs with the help of physicians. With increasing economic
      pressure, these negotiations have a tremendous ability to decrease the cost of
      trauma care. In the past, physicians have taken no responsibility for implant
      pricing which has made cost control difficult. The reasons have been
      multifactorial. However, industry surgeon consulting fees, research support, and
      surgeon comfort with certain implant systems have played a large role in slowing
      adoption of cost-control measures. With the advent of physician gainsharing and
      comanagement agreements, physicians now have impetus to change. At our facility,
      we have used 3 methods for cost containment since 2009: dual vendor, matrix
      pricing, and sole-source contracting. Each has been increasingly successful,
      resulting in massive savings for the institution. This article describes the
      process and benefits of each model.

PMID- 27870674
TI  - Impact of Hospital-Employed Physician Assistants on a Level II Community-Based
      Orthopaedic Trauma System.
AB  - OBJECTIVES: The American Academy of Orthopedic Surgeons and the Orthopedic Trauma
      Association have released guidelines for the provision of orthopedic trauma
      services such as adequate stipends, designated operating rooms, ancillary staff,
      and guaranteed reimbursement for indigent care. One recommendation included a
      provision for hospital-based physician assistants (PAs). Given current
      reimbursement arrangements, PA collections for billable services may not meet
      their salary and benefit expenses. However, their actions may indirectly affect
      emergency room, operating room, and hospital reimbursement and patient care
      itself. The purpose of our study is to define the true impact of hospitalbased
      PAs on orthopaedic trauma care at a level II community hospital. DESIGN:
      Retrospective case series. SETTING: Level II trauma center.
      PATIENTS/PARTICIPANTS: One thousand one hundred four trauma patients with
      orthopaedic injuries. INTERVENTION: PA involvement. MAIN OUTCOME MEASUREMENTS:
      Emergency room data such as triage time, time until seen by the orthopedic
      service, and total emergency room time was recorded. Operating room data such as
      time to surgery, set-up time, total operating time, and out of room time was
      entered as well. Charts were reviewed to determine if patients were given
      postoperative antibiotics and Deep Venous Thrombosis (DVT) prophylaxis.
      Intraoperative and postoperative complications were noted, and lengths of stay
      were calculated for all patients. RESULTS: At our institution, PA collections
      from patient care cover only 50% of their costs for salary and benefits. However,
      with PA involvement, trauma patients with orthopedic injuries were seen 205
      minutes faster (P = 0.006), total Emergency Room (ER) time decreased 175 minutes
      (P = 0.0001), and time to surgery improved 360 minutes (P . 0.03). Operating room
      parameters were minimally improved, but postoperative DVT prophylaxis increased
      by a mean of 6.73% (P = 0.0084), postoperative antibiotic administration
      increased by 2.88% (P = 0.0302), and there was a 4.67% decrease in postoperative
      complications (P = 0.0034). Average length of stay decreased by 0.61 days (P =
      0.27). CONCLUSIONS: Although the PA's collections do not cover their costs, the
      indirect economic and patient care impacts are clear. By increasing emergency
      room pull through and decreasing times to Operating Room (OR), operative times,
      lengths of stay, and complications, their existence is clearly beneficial to
      hospitals, physicians, and patients as well. LEVEL OF EVIDENCE: Economic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 27870675
TI  - Comanagement and Gainsharing Opportunities for Independent Physicians.
AB  - Gainsharing and comanagament programs are both successful means of achieving
      physician buy-in for all cost containment programs in Orthopaedic Trauma. Under
      comanagement agreements, physicians are reimbursed for their time and
      intellectual efforts in program and algorithm creation. The cost is minimal for
      the hospital in return for the millions of dollars in savings they achieve.
      Gainsharing models can incentivize physicians to quickly adopt cost-effective
      implant choices, care plans, and program development. Hospital systems keep the
      majority of the profits, patients, and insurance carriers benefit from the cost
      savings and physicians receive remuneration for their efforts. Careful attention
      must be paid to the legal issues surrounding the Federal Anti-Kickback Statute,
      the Civil Monetary Penalty Law, and the Physician Self-Referral Law when setting
      up these agreements. The keys to success for these programs are the presence of a
      physician champion, economic transparency for both physicians and hospitals,
      accurate data collection, and adequate economic incentive for physicians to drive
      change in practice patterns.

PMID- 27870676
TI  - Bundled Payments for Care Improvement: Lessons Learned in the First Year.
AB  - The Bundled Payments for Care Improvement (BPCI) initiative is the latest cost
      saving program developed by the Center for Medicare and Medicaid Innovation. This
      model is intended to create a system for higher quality and more coordinated care
      at a lower cost to Medicare. It is currently an optional program for physician
      groups, hospitals and post-acute care providers to benefit financially from
      improved care models and cost containment measures. Under the initiative,
      organizations enter into payment arrangements that include financial and
      performance accountability for episodes of care. Under this initiative, there are
      certain fraud and abuse waivers in place that allow gainsharing among BPCI
      organizations and approved providers so long as certain requirements are met. Our
      practice entered this initiative for total joint arthroplasty episodes of care as
      well as the hip and femur fracture episode of care. The first year experience
      demonstrated that a significant learning curve is required. Keys for success
      include appropriate patient selection for elective surgery, implant pricing
      control, adherence to preoperative and postoperative protocols, diligent postcare
      care management, and appropriate choice of metrics to maximize gainsharing
      potential. Ultimately, the BPCI program has been a successful venture, saving our
      hospitals over $1.6 million in 2015. In the process, this provided an additional
      revenue stream for our physicians while decreasing the overall cost of care.

PMID- 27870677
TI  - From the Guest Editor: Interventional Oncology: The Fourth Pillar of Oncology.

PMID- 27870679
TI  - New Developments in Interventional Oncology: Liver Metastases From Colorectal
      Cancer.
AB  - Colorectal cancer is the third leading cause of cancer death in the United
      States. Although hepatic excision is the first-line treatment for colorectal
      liver metastasis (CRLM), few patients are candidates. Locoregional therapy (LRT)
      encompasses minimally invasive techniques practiced by interventional radiology.
      These include ablative treatments (radiofrequency ablation, microwave ablation,
      and cryosurgical ablation) and transcatheter intra-arterial therapy (hepatic
      arterial infusion chemotherapy, transarterial "bland" embolization, transarterial
      chemoembolization, and radioembolization with yttrium 90). The National
      Comprehensive Cancer Network recommends LRT for unresectable CRLM refractory to
      chemotherapy. The following is a review of LRT in CRLM, including salient
      features, advantages, limitations, current roles, and future considerations.

PMID- 27870680
TI  - Liver Metastases From Noncolorectal Malignancies (Neuroendocrine Tumor, Sarcoma,
      Melanoma, Breast).
AB  - Patients with noncolorectal hepatic metastases often face limited treatment
      options and a dismal prognosis. Over the last decade, the advent of targeted
      immunotherapies has transformed the treatment of certain metastatic cancers, such
      as sarcoma and melanoma; however, these patients eventually develop resistance.
      Metastatic sarcoma, melanoma, and breast and neuroendocrine tumors are
      notoriously treatment resistant once they have metastasized to the liver. For
      these cancers, minimally invasive transarterial and ablation therapies have
      emerged as safe, palliative therapies that can provide symptom control and even
      prolong survival.

PMID- 27870678
TI  - Interventional Oncology in Hepatocellular Carcinoma: Progress Through Innovation.
AB  - The clinical management of hepatocellular carcinoma has evolved greatly in the
      last decade mostly through recent technical innovations. In particular, the
      application of cutting-edge image guidance has led to minimally invasive
      solutions for complex clinical problems and rapid advances in the field of
      interventional oncology. Many image-guided therapies, such as transarterial
      chemoembolization and radiofrequency ablation, have meanwhile been fully
      integrated into interdisciplinary clinical practice, whereas others are currently
      being investigated. This review summarizes and evaluates the most relevant
      completed and ongoing clinical trials, provides a synopsis of recent innovations
      in the field of intraprocedural imaging and tumor response assessment, and offers
      an outlook on new technologies, such as radiopaque embolic materials. In
      addition, combination therapies consisting of locoregional therapies and systemic
      molecular targeted agents (e.g., sorafenib) remain of major interest to the field
      and are also discussed. Finally, we address the many substantial advances in
      immune response pathways that have been related to the systemic effects of
      locoregional therapies. Knowledge of these new developments is crucial as they
      continue to shape the future of cancer treatment, further establishing
      interventional oncology along with surgical, medical, and radiation oncology as
      the fourth pillar of cancer care.

PMID- 27870681
TI  - Kidney Cancer.
AB  - The number of new cases of renal cell carcinoma has been steadily increasing
      since the 1960s, reaching 62,000 and 89,000 annually in the United States and
      Europe, respectively, in 2016. The current standard of care for early-stage
      disease is nephron-sparing surgery, which has a demonstrated long-term disease
      free survival and an acceptable safety profile. Technical developments (thin,
      powerful probes and real-time image guidance systems) have allowed image-guided
      percutaneous ablation to become a viable option for stage I renal cell carcinoma.
      Because of the widespread use of cross-sectional imaging, most renal tumors (75%)
      are indeed detected incidentally at stage I (75%). As a result, ablation is a
      potentially curable intervention and one that could mitigate surgical risks. All
      3 ablative modalities (radiofrequency ablation, microwave ablation, and
      cryoablation) have been extensively applied. The utilization of ablation was
      initially hampered by the lack of prospective, long-term oncologic data. As a
      result, ablation was reserved for specific subgroups of patients, for example,
      patients with solitary kidney, chronic kidney disease, or bilateral disease; poor
      surgical candidates; or patients with syndromes that predispose them to renal
      cell cancer. Recently, however, studies on percutaneous ablation for early-stage
      renal cancer have yielded prospective, long-term oncologic data, affirming the
      earlier, lower-level-evidence studies. The reported efficacy of ablation for
      stage I renal cancer (especially cryoablation) appears to rival that of the
      accepted standard of care (nephron-sparing surgery), whereas its safety profile
      is a decided advantage. In conclusion, image-guided percutaneous ablation should
      be considered a viable, curative option for stage IA renal cell carcinoma.

PMID- 27870682
TI  - Advances in Interventional Oncology: Lung Cancer.
AB  - Image-guided lung intervention in the oncologic patient includes transthoracic
      needle biopsy, thermal ablation, fiducial placement, and tunneled pleural
      catheter placement and is made possible by technical advancements in computed
      tomography, fluoroscopy, and ultrasound technology, as well as the proliferation
      of available thermal ablation modalities such as radiofrequency, microwave, and
      cryoablation. With increasingly earlier cancer diagnoses being made and a greater
      patient demand for minimally invasive therapies, interventional oncology has many
      options to offer the patient with thoracic malignancies. The indications,
      technique, outcomes, and complications of these diagnostic and therapeutic
      procedures are described in detail in this review article.

PMID- 27870683
TI  - Increasing Role of Image-Guided Ablation in the Treatment of Musculoskeletal
      Tumors.
AB  - In the last decade, percutaneous treatment of musculoskeletal (MSK) tumors has
      become more established in routine clinical care while also undergoing a number
      of advancements. Ablative techniques to palliate painful skeletal metastases have
      gained wide acceptance, while goals for ablation have evolved to include local
      control of oligometastases and desmoid tumors. Bone consolidation or augmentation
      is now frequently used in conjunction with or instead of ablation of skeletal
      tumors to stabilize pathologic fractures or prevent further morbidity that could
      result from fractures caused by tumor progression. These procedures have
      traditionally been performed with cement injection, although additional
      percutaneous consolidation or stabilization devices have been developed.
      Techniques to monitor the ablation zone and adjacent structures intraprocedurally
      are now applied to increase the number of tumors amenable to treatment. These
      include methods to depict, displace, or monitor critical structures adjacent to
      targeted MSK tumors. Finally, the role of ablation in the comprehensive care of
      patients with MSK tumors continues to change with the evolving triage of patients
      between radiation therapy, surgical resection and stabilization, and percutaneous
      ablative and consolidative management.

PMID- 27870684
TI  - Palliative Interventional Oncology.
AB  - Interventional oncologists are playing an ever greater role in improving the
      quality of life of their patients through minimally invasive procedures, many of
      which can be performed on an outpatient basis. Some of the most common palliative
      procedures currently performed will be discussed including management of
      intractable ascites and pleural effusions, neurolytic plexus blocks, and
      palliation of pain and bleeding associated with metastatic tumors.

PMID- 27870685
TI  - The Importance of Biopsy in the Era of Molecular Medicine.
AB  - Recent advances in the molecular characterization of cancers have triggered
      interest in developing a new taxonomy of disease in oncology with the goal of
      using the molecular profile of a patient's tumor to predict response to
      treatment. Image-guided needle biopsy is central to this "precision medicine"
      effort. In this review, we first discuss the current role of biopsy in relation
      to clinical examples of molecular medicine. We then outline important bottlenecks
      to the advancement of precision medicine and highlight the potential role of
      image-guided biopsy to address these challenges.

PMID- 27870687
TI  - When is it ok to use a splint versus cast and what remodeling can one expect for
      common pediatric forearm fractures.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an overview of common
      pediatric forearm fractures, clarify the descriptions used to identify and
      thereby appropriately treat them with a splint or cast, and explain osseous
      remodeling that is unique to the skeletally immature. RECENT FINDINGS: Recent
      literature addresses the gap in standard treatment protocols. There is
      variability in the management of pediatric forearm fractures because of the
      multiple subspecialty physicians that care for children's fractures and a lack of
      well established guidelines. CONCLUSION: The following review will expound upon
      the assortment of pediatric forearm fractures, address suitable treatment
      options, and illustrate the expected restoration of bony deformity in an effort
      to update practitioners of the most recent advances in research and clinical
      practice of this common orthopedic injury.

PMID- 27870686
TI  - Era of a Single Population-Based Payment to a Cancer Center: Delivering the Value
      of Interventional Oncology in Accountable Care Organizations.
AB  - To curtail increasing health care costs, the government has ushered in the era of
      the Accountable care organization (ACO). The purposes of this review are to
      evaluate the effects the ACO will have on the practice of interventional oncology
      and its role in cancer care and to explore methods to assimilate. Proposed action
      points include integration into the modern-day cancer center, adoption of an
      outpatient clinic, mandatory performance measures, and workflow and cost
      analysis. If adaptations are made, interventional oncology can continue its role
      in cancer treatment, will provide more effective care, and reach more patients in
      the new ACO.

PMID- 27870688
TI  - Clinical aspects of Zika virus.
AB  - PURPOSE OF REVIEW: Zika virus (ZIKV) is a mosquito-borne flavivirus that has
      caused a sudden and explosive outbreak in South America and the Caribbean in the
      last year, and has been declared a public health emergency by the WHO. As ZIKV
      afflicts previously naive populations, more severe clinical presentations and
      sequelae have been observed. A specific emphasis has been placed on the
      neurological effects in infants resulting from viral exposure in utero. RECENT
      FINDINGS: Acute onset of ZIKV disease is seen in approximately 20% of cases,
      whereas most individuals (80%) exposed are asymptomatic. Presentation of illness
      is typically mild, with disease spectrum ranging from arthralgia and rash to
      encephalitis, myelitis, and Guillain-Barre syndrome. Infants have been uniquely
      impacted by the current outbreak with significant congenital exposure resulting
      in permanent neurological defects and developmental complications. SUMMARY: The
      current ZIKV outbreak has illustrated the emergent capabilities of mosquito-borne
      viruses and the teratogenic nature of ZIKV. Causality and risk factors associated
      with severe manifestations, as well as chronic sequelae, have yet to be
      determined. Extensive research is required to understand the molecular mechanisms
      of infection, develop improved assays for differential diagnosis, and improve
      overall knowledge of the spectrum of ZIKV disease in order to develop modes of
      prevention and treatment.

PMID- 27870689
TI  - Zika virus and diagnostics.
AB  - PURPOSE OF REVIEW: The purpose of this review is to present what is known about
      the Zika virus (ZIKV) at the time of writing this review. The viral structure and
      its phylogeny, as well as the limitations of current available techniques used
      for diagnosis, are discussed. RECENT FINDINGS: Crystallography and cryo-electron
      microscopy of the whole ZIKV, or a few of its proteins, are confirming its
      overall antigenic relatedness to other flaviviruses. Sequencing has revealed its
      dynamic genetic variation and has placed the Western cluster of Zika isolates
      within the Asian phylogenic tree. Genetic codon mutations, although highly
      prevalent, do not usually translate into modifications at amino acid or proteomic
      levels, revealing conserved enzymatic functions that could potentially be
      addressed therapeutically. Clinical characterization of ZIKV infection is
      complicated because of symptoms similar to dengue and chikungunya. Diagnosis
      requires specialized laboratories with costly reagents and highly trained
      personnel. Although commercial labs are now offering ZIKV diagnostic tests, most
      of them are not fully tested in comparison with standard molecular techniques
      standardized at CDC and local health departments. We are still in desperate need
      of simpler diagnostic tests that better discriminate ZIKV from coendemic
      arboviruses. SUMMARY: The area of better Zika diagnostic assays is a rapidly
      developing field with the public attention directed to this epidemic. Academic
      interest in this topic is driving fast disclosure of information in peer-reviewed
      journals and grey papers via web-based forums. We expect in the near future that
      new promising strategies for improved Zika diagnostics will translate into
      preventive and therapeutic tools.

PMID- 27870690
TI  - Advances in pediatric hematology/oncology.

PMID- 27870691
TI  - Screw Stripping After Repeated Cortical Screw Insertion-Can We Trust the
      Cancellous "Bailout" Screw?
AB  - BACKGROUND: During osteosynthesis standard nonlocking cortical screws often
      require reinsertion, raising concern over possible decrease in their
      effectiveness. This study aims to quantify that potential loss of fixation with
      reinsertions as well as examine the ability of a cancellous "bailout screw" to
      regain insertion torque in a previously stripped screw hole. METHODS: Four
      different types of bone surrogates were chosen to represent normal cortical bone,
      osteoporotic cortical bone, high-density (normal) cancellous bone, and low
      density (osteoporotic) cancellous bone; nonlocked 3.5-mm cortical screws were
      inserted into the predrilled holes 1, 2, 3, 4, or 5 times before being torqued
      maximally to the point of stripping. A 4.0-mm cancellous "bailout" screw was then
      placed into the same hole and torqued until stripping. Torque was measured
      continuously using a torque-measuring screwdriver and maximal insertion torque
      (MIT) of 3.5 and 4.0 screws before stripping was recorded. RESULTS: MIT decreased
      with reinsertion of nonlocked cortical screws. By the third reinsertion in all
      but the normal bone surrogates, the screws lost approximately one third to one
      half of their original MIT (50%-71% of original torque). The bailout screw
      succeeded in restoring the original MIT in the osteoporotic cancellous bone
      surrogate and the normal cortical bone surrogate. In the normal cancellous and
      osteoporotic cortical bone surrogates, the bailout screw was only able to restore
      an average of 50% (range 31%-63%) of the original MIT. CONCLUSIONS: Screw
      reinsertion may significantly reduce the MIT of 3.5-mm nonlocked cortical screws.
      Use of the bailout cancellous screw for a stripped cortical screw should be
      expected to restore MIT only in normal cortical bone and osteoporotic cancellous
      bone. In other scenarios, the bailout screw should not be expected to uniformly
      restore full insertion torque.

PMID- 27870692
TI  - Wide Variation of Surgical Cost in the Treatment of Periarticular Lower Extremity
      Injuries Between 6 Fellowship-Trained Trauma Surgeons.
AB  - OBJECTIVES: We hypothesized that negligible surgical material cost variation
      exists between traumatolgists for treatment of bimalleolar ankle and bicondylar
      tibial plateau fractures. DESIGN: Retrospective medical record review. SETTING:
      Academic level 1 Trauma Center; 2-year period. PATIENTS/PARTICIPANTS: Current
      Procedure Terminology codes for open treatment of bimalleolar ankle and
      bicondylar tibial plateau fractures identified patients. Patients who had
      operative treatment of other injuries under the same anesthetic session were
      excluded. Only definitive treatment procedures were analyzed. INTERVENTION: We
      analyzed the intraoperative material costs of these procedures and compared them
      between surgeons. This analysis was done with a newly developed proprietary
      program designed for inventory and cost analysis. MAIN OUTCOME MEASUREMENTS: Mean
      and median total case material costs were compared using one-way analysis of
      variance. Individual items that significantly increased costs were identified.
      RESULTS: We identified 88 bimalleolar ankle and 46 bicondylar tibial plateau
      fractures treated by 6 surgeons. The mean intraoperative material cost per
      bimalleolar ankle fracture was $1099. The least expensive surgeon's mean case
      cost was $613, which was significantly less than the most expensive surgeon's
      $2243 (P = 0.009). The median cost range was $598-$784. The top quartile of cases
      resulted in 57% of overall material cost for ankle fractures. The mean
      intraoperative material cost per bicondylar tibial plateau fracture was $3219
      (range $1839-$4088, P = 0.064). The range of median costs ($1826-$3989) was
      significantly wider than for ankle fractures. Bone void fillers, locking plates,
      adjunctive external fixators, mini-fragment locking plates, cannulated screws,
      single-use taps, guidewires, and drill bits all substantially increased costs.
      CONCLUSION: This study demonstrated variation in intraoperative material cost
      between 6 traumatologists resulting from practice variations despite similar
      specialty training. The cost differences resulting from practice variation reveal
      potential savings through increased standardization of surgical care for similar
      injuries. We identified high-cost items, which could lead to cost savings if used
      only when they will have clinical benefit.

PMID- 27870693
TI  - Limb Salvage With Intrepid Dynamic Exoskeletal Orthosis Versus Transtibial
      Amputation: A Comparison of Functional Gait Outcomes.
AB  - OBJECTIVES: To determine if there is a difference in functional gait outcomes
      between patients with limb injuries treated with either transtibial amputation or
      limb preservation with the Intrepid Dynamic Exoskeletal Orthosis. DESIGN:
      Retrospective prognostic study. SETTING: Tertiary referral military hospital.
      PATIENTS: This study included 10 transtibial amputees and 10 limb preservation
      patients using the Intrepid Dynamic Exoskeletal Orthosis who were matched by body
      mass index after excluding for nontraumatic, proximal ipsilateral, contralateral,
      spine, or traumatic brain injuries. Transtibial amputation patients were also
      excluded if they did not have a gait study between 6 and 12 months after
      independent ambulation. Limb preservation were excluded if they did not complete
      the "Return to Run" program. INTERVENTIONS: An observational study of functional
      outcomes using instrumented gait analysis. OUTCOME MEASURES: Spatiotemporal,
      kinetic (vertical ground reaction force), unified deformable power, work, and
      efficiency. RESULTS: Limb preservation patients walked with a significantly
      slower cadence (P = 0.036) and spent less time on their affected limb in stance
      (P = 0.045), and longer in swing (P = 0.019). Amputees had significantly
      increased maximum positive power in both limbs (P = 0.004 and P = 0.029) and
      increased maximum negative power on the unaffected limb (P = 0.035). Amputees had
      significantly increased positive and negative work in the affected limb (P =
      0.0009 and P = 0.014) and positive work in the unaffected limb (P = 0.042). There
      was no significant difference in the kinetic data or efficiency. CONCLUSIONS:
      Limb preservation patients spend less time on their affected limb as a percentage
      of the gait cycle. The unified deformable power demonstrated more dynamic gait in
      amputees, with peak values closer to normative data. LEVEL OF EVIDENCE:
      Therapeutic level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 27870695
TI  - Validity and Reliability of a Submaximal Intermittent Running Test in Elite
      Australian Football Players.
AB  - Veugelers, KR, Naughton, GA, Duncan, CS, Burgess, DJ, and Graham, SR. Validity
      and reliability of a submaximal intermittent running test in elite Australian
      football players. J Strength Cond Res 30(12): 3347-3353, 2016-The aim of this
      article was to determine the validity and reliability of a submaximal
      intermittent running (SIR) test in elite Australian rules football (ARF) players.
      Heart rate (HR) responses of 38 elite ARF players to both the SIR and the yo-yo
      intermittent recovery 2 (YYIR2) tests were compared over 2 trials. Linear
      regression analysis was used to examine the relationship between SIR test HR
      responses and YYIR2 test performance. Heart rate responses of 25 elite ARF
      players to the SIR test were monitored over 3 trials. Day-to-day reliability was
      determined using intraclass correlation coefficient (ICC), typical error of
      measurement, coefficient of variation (CV), and smallest worthwhile change. Large
      inverse correlations were reported between 2-, 3-, and 4-minute HR during the SIR
      test and YYIR2 test distance (r = -0.58 to -0.61, p < 0.01). Heart rate recovery
      after 2 and 3 minutes of the SIR test was moderately correlated to YYIR2 distance
      (r = 0.32-0.35, p <= 0.05). Strong correlations for ICC (r = 0.90-0.97) and low
      CV (1.3-9.2%) were reported for all HR variables. Monitoring HR during the SIR
      test is a valid and reliable indicator of YYIR2 test performance in elite ARF
      players. These findings support the use of the SIR test as a regular and non
      fatiguing indicator of intermittent running capacity.

PMID- 27870694
TI  - Does Intrasession Concurrent Strength and Aerobic Training Order Influence
      Training-Induced Explosive Strength and V[Combining Dot Above]O2max in
      Prepubescent Children?
AB  - Alves, AR, Marta, C, Neiva, HP, Izquierdo, M, and Marques, MC. Does intrasession
      concurrent strength and aerobic training order influence training-induced
      explosive strength and V[Combining Dot Above]O2max in prepubescent children?. J
      Strength Cond Res 30(12): 3267-3277, 2016-The aim of this study was to analyze
      the interference of strength and aerobic training order over an 8-week period on
      explosive skills and maximal oxygen uptake (V[Combining Dot Above]O2max) in
      prepubescent children. One hundred twenty-eight prepubescent children aged 10-11
      years (10.9 +/- 0.5 years) were randomly selected and assigned to 1 of the 3
      groups: intrasession concurrent aerobic before (GAS: n = 39) or after strength
      training (GSA: n = 45) or control group (GC: n = 44; no training program). The GC
      maintained their baseline level performance, and training-induced differences
      were found in the experimental groups. Increases were found in the 1-kg and 3-kg
      medicine ball throws: GAS: +3%, +5.5%, p <= 0.05, p < 0.001; GSA: +5.7%, +8.7%, p
      < 0.001, respectively; in the counter movement jump height and standing long jump
      length: GAS: +6.5%, +3.4%, p <= 0.05; GSA: +7%, +4.5%, p < 0.001, respectively;
      in the 20-m shuttle-run time: GAS: +2.3%; GSA: +4.6%, p < 0.001; and, in the
      V[Combining Dot Above]O2max: GAS: +7.3%, p < 0.001; GSA: +3.8%, p < 0.001 from
      pretraining to post-training. All programs were effective, but GSA produced
      better results than GAS for muscle strength variables, and GAS produced better
      results than GSA for aerobic capacity variables. The present study explored an
      unknown issue and added useful information to the literature in this area. These
      training methods should be taken into consideration to optimize explosive
      strength and cardiorespiratory fitness training in school-based programs and
      sports club programs.

PMID- 27870696
TI  - Strength and Conditioning and Concurrent Training Practices in Elite Rugby Union.
AB  - Jones, TW, Smith, A, Macnaughton, LS, and French, DN. Strength and Conditioning
      and Concurrent Training Practices in Elite Rugby Union. J Strength Cond Res
      30(12): 3354-3366, 2016-There is limited published research on strength and
      conditioning (S&C) practices in elite rugby union (RU). Information regarding
      testing batteries and programme design would provide valuable information to both
      applied practitioners and researchers investigating the influence of training
      interventions or preperformance strategies. The aim of this study was to detail
      the current practices of S&C coaches and sport scientists working in RU. A
      questionnaire was developed that comprised 7 sections: personal details, physical
      testing, strength and power development, concurrent training, flexibility
      development, unique aspects of the programme, and any further relevant
      information regarding prescribed training programmes. Forty-three (41 men, 2
      women; age: 33.1 +/- 5.3 years) of 52 (83%) coaches responded to the
      questionnaire. The majority of practitioners worked with international level
      and/or professional RU athletes. All respondents believed strength training
      benefits RU performance and reported that their athletes regularly performed
      strength training. The clean and back squat were rated the most important
      prescribed exercises. Forty-one (95%) respondents reported prescribing plyometric
      exercises and 38 (88%) indicated that periodization strategies were used. Forty
      two (98%) practitioners reported conducting physical testing, with body
      composition being the most commonly tested phenotype. Thirty-three (77%)
      practitioners indicated that the potential muted strength development associated
      with concurrent training was considered when programming and 27 (63%) believed
      that strength before aerobic training was more favorable for strength development
      than vice versa. This research represents the only published survey to date of
      S&C practices in northern and southern hemisphere RU.

PMID- 27870697
TI  - Functional Movement Screen Factorial Validity and Measurement Invariance Across
      Sex Among Collegiate Student-Athletes.
AB  - Gnacinski, SL, Cornell, DJ, Meyer, BB, Arvinen-Barrow, M, and Earl-Boehm, JE.
      Functional Movement Screen factorial validity and measurement invariance across
      sex among collegiate student-athletes. J Strength Cond Res 30(12): 3388-3395,
      2016-The Functional Movement Screen (FMS) is a screening tool used to evaluate
      functional movement quality and subsequent musculoskeletal injury risk. Despite
      recent research on the factorial validity of the FMS, no confirmatory factor
      analysis (CFA) has been conducted to examine measurement invariance across sex
      among student-athletes. The primary purpose of the current study was to confirm
      the factor structure of the FMS measurement model in a collegiate student-athlete
      population. It was hypothesized that the 1-factor model would demonstrate better
      model fit than the recently proposed 2-factor model. The secondary purpose of the
      study was to examine FMS measurement invariance across sex using the previously
      identified measurement model. It was hypothesized that FMS measurement invariance
      would hold across sex. Male (n = 88) and female (n = 88) collegiate student
      athletes completed FMS screening during the off-season. Factorial validity was
      examined using CFA procedures, and model parameters were estimated using maximum
      likelihood estimation. Measurement invariance was examined by comparison of fit
      indices between hierarchically constrained models. Results revealed support for
      both the 1- and the 2-factor models; however, the 2-factor model failed to fit
      the data significantly better than the 1-factor model. Results also indicated
      that measurement invariance did not hold across sex, indicating that the FMS sum
      score construct is not measured equivalently in male and female populations.
      Collectively, results provide evidence for the use of the unidimensional FMS sum
      score among collegiate student-athletes, yet prompt caution because it relates to
      the evaluation of sex differences in sum or movement pattern scores.

PMID- 27870698
TI  - Risk Factors for Injury Among Japanese Collegiate Players of American Football
      Based on Performance Test Results.
AB  - Iguchi, J, Watanabe, Y, Kimura, M, Fujisawa, Y, Hojo, T, Yuasa, Y, Higashi, S,
      and Kuzuhara, K. Risk factors for injury among Japanese collegiate players of
      American football based on performance test results. J Strength Cond Res 30(12):
      3405-3411, 2016-The purpose of this study was to identify how risk factors for
      injury during American football are related to players' physical strength as
      determined using typical performance tests. One hundred 53 Japanese collegiate
      players of American football were recruited for this study. Eight potential risk
      factors were evaluated: position (skill vs. lineman), body mass index, back squat
      one-repetition maximum, vertical jump height, power, height, body weight, and
      previous injury. Using multivariate Cox regression, we examined how these factors
      were associated with knee sprain, ankle sprain, and hamstring strain. We recorded
      63 injuries (17 knee sprains, 23 ankle sprains, and 23 hamstring strains).
      Players with higher power were at significantly greater risk for knee sprains (p
      = 0.04), those with low power had a significantly higher incidence of ankle
      sprain (p = 0.01), and vertical jump height was a significant predictor of
      hamstring strain (p = 0.02). We identified several independent predictors of
      injuries associated with American football. Our findings may contribute to the
      development of effective screening tests and prevention exercises.

PMID- 27870700
TI  - Patterns of Recurrence and Clinical Outcome of Patients With Stage IIIC to Stage
      IV Epithelial Ovarian Cancer in Complete Response After Primary Debulking Surgery
      Plus Chemotherapy or Neoadjuvant Chemotherapy Followed by Interval Debulking
      Surgery: An Italian Multicenter Retrospective Study.
AB  - OBJECTIVE: The objective of this retrospective study was to assess the clinical
      outcome of patients with advanced epithelial ovarian cancer in complete response
      after primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by
      interval debulking surgery (IDS]). METHODS: The authors reviewed the hospital
      records of 384 patients who underwent PDS (n = 322) or IDS (n = 62) and who were
      in complete response after primary treatment. RESULTS: Optimal (residual disease
      [RD] < 1 cm) and complete (no gross RD) cytoreduction rates were higher after IDS
      than after PDS (71.0% vs 55.9%; P = 0.001 and 51.6% vs 35.7%, respectively; P =
      0.02). Tumor recurred in 73.0% of the 322 complete responders after PDS versus
      87.1% of the 62 complete responders after IDS (P = 0.01). The IDS group showed a
      higher recurrence rate within 6 months (11.3% vs 3.1%: P = 0.01) and a trend to
      higher recurrence rate between 6 and 12 months (30.6% vs 19.9%). Tumor recurred
      in 57.4% of the 115 completely cytoreduced patients after PDS versus 87.5% of the
      32 completely cytoreduced patients after IDS (P = 0.001). The IDS group showed a
      trend to higher recurrence rate within 6 months (6.2% vs 1.7%) and a higher
      recurrence rate between 6 and 12 months (37.5% vs 15.6%; P = 0.01). Two-year, 5
      year, and 7-year progression-free survival were 65.8%, 40.8%, and 39.3% for
      completely cytoreduced patients after PDS versus 43.8%, 12.5%, and 12.5% for
      completely cytoreduced patients after IDS (P = 0.001); and 2-year, 5-year, and 7
      year overall survival were 96.4%, 69.3%, and 50.4% for the former versus 87.1%,
      41.8%, and 32.6% for the latter (P = 0.001). CONCLUSIONS: The clinical outcome of
      completely cytoreduced patients was significantly better for PDS group than for
      IDS group, and therefore, the achievement of no gross RD after surgery seemed to
      have a different prognostic relevance for the 2 groups.

PMID- 27870699
TI  - Resistance Training Alters the Proportion of Skeletal Muscle Fibers but Not Brain
      Neurotrophic Factors in Young Adult Rats.
AB  - Antonio-Santos, J, Ferreira, DJS, Gomes Costa, GL, Matos, RJB, Toscano, AE,
      Manhaes-de-Castro, R, and Leandro, CG. Resistance training alters the proportion
      of skeletal muscle fibers but not brain neurotrophic factors in young adult rats.
      J Strength Cond Res 30(12): 3531-3538, 2016-Resistance training (RT) is related
      to improved muscular strength and power output. Different programs of RT for rats
      have been developed, but peripheral and central response has not been evaluated
      directly in the same animal. To test the hypothesis that RT induces central and
      peripheral adaptations, this study evaluated the effects of a RT on the
      performance of a weekly maximum overload test, fiber-type typology, and brain
      neurotrophic factors in young adult rats. Thirty-one male Wistar rats (65 +/- 5
      days) were divided in 2 groups: nontrained (NT, n = 13) and trained (T, n = 18).
      Trained group was submitted to a program of RT ladder climbing, gradually added
      mass, 5 days per week during 8 weeks at 80% of individual maximum overload. This
      test was weekly performed to adjust the individual load throughout the weeks for
      both groups. After 48 hours from the last session of exercise, soleus and
      extensor digital longus (EDL) muscles were removed for myofibrillar ATPase
      staining analysis. Spinal cord, motor cortex, and cerebellum were removed for RT
      PCR analysis of BDNF and insulin-like growth factor-1 (IGF-1) gene expression. In
      EDL muscle, T animals showed an increase in the proportion of type IIb fibers and
      a reduction of type IIa fibers. Insulin-like growth factor-1 gene expression was
      reduced in the cerebellum of T animals (NT: 1.025 +/- 0.12; T: 0.57 +/- 0.11).
      Our data showed that 8 weeks of RT were enough to increase maximum overload
      capacity and the proportion of glycolytic muscle fibers, but there were no
      associations with the expression of growth neurotrophic factors.

PMID- 27870701
TI  - A New MicroRNA Expression Signature for Cervical Cancer.
AB  - BACKGROUND: Cervical cancer is the second most common cancer among women
      worldwide. The potential of microRNAs as novel biomarkers in cervical cancer is
      growing. OBJECTIVES: In this study, we investigated the functions and targets of
      miR-466 in cervical cancer tissues. METHODS: Fresh cervical tissues were obtained
      from 157 patients with cervical cancer, cervical intraepithelial neoplasia (CIN),
      and healthy controls, and the tissues were immediately frozen in liquid nitrogen
      until use. The RNA was extracted and quantitative real-time polymerase chain
      reaction (PCR) was performed. RESULTS: A total of 157 participants were
      summarized, including 56 patients with cervical cancer, 60 patients with CIN, and
      49 healthy controls. The expression levels of miR-466 in cervical cancers (0.68)
      were higher than that in healthy controls (0.082) (P < 0.01). The average fold
      changes of miR-466 in the patients with CIN group and people group were 0.28 and
      0.082, respectively (P < 0.01). It was a statistically significant difference in
      patients with lymph node involvement (P = 0.022). However, the expression of miR
      466 was not correlated with International Federation of Gynecology and Obstetrics
      stages, tumor size, or vascular invasion (P = 0.506, P = 0.667, and P = 0.108,
      respectively). CONCLUSIONS: Our results indicate that the aberrant expression of
      miR-466 is closely associated with the occurrence and development of cervical
      cancer.

PMID- 27870702
TI  - Synchronous Ovarian and Appendiceal Mucinous Neoplasms in the Absence of
      Pseudomyxoma Peritonei.
AB  - BACKGROUND: Synchronous ovarian/appendiceal mucinous neoplasms sometimes occur in
      the absence of clinical pseudomyxoma peritonei (PMP), which raises a question
      about whether the 2 tumors could be independent. METHODS: We identified 11 cases
      of synchronous ovarian/appendiceal mucinous neoplasms without PMP and
      subclassified them into groups 1 and 2 based on the presence or absence of
      microscopic peritoneal/ovarian surface mucin deposits. A 7-marker panel (CK7,
      CK20, CDX2, PAX8, MUC1, MUC2, and MUC5AC) immunohistochemistry was performed on
      both tumors. RESULTS: Between the 2 groups, there were no significant differences
      in age, laterality, size, and histology of ovarian/appendiceal tumors. In group
      1, 2 of 4 cases developed PMP later, and both had ovarian surface and
      contralateral ovarian involvement and appendiceal perforation with microscopic
      mucin deposits on the peritoneum. No patients in group 2 developed PMP. All group
      1 cases showed a high degree of concordance of immunoprofile between the
      synchronous tumors, with an identical expression of appendiceal pattern in
      greater than 90% of the markers. In group 2, only 1 of 7 cases showed concordance
      in all markers. CONCLUSIONS: If peritoneal mucin deposits present, even
      microscopic and acellular, the synchronous tumors are most likely of a single
      appendiceal origin. Otherwise, they are more heterogeneous, and some may be truly
      dual primaries.

PMID- 27870704
TI  - Clinical Outcomes for Stereotactic Ablative Radiotherapy in Oligometastatic and
      Oligoprogressive Gynecological Malignancies.
AB  - OBJECTIVES: We report single-institution clinical outcomes of women treated with
      stereotactic ablative radiotherapy (SABR) for oligometastatic or progressive
      gynecological malignancies. MATERIALS AND METHODS: From 2009 to 2015, 47 lesions
      from 28 patients were treated with SABR and retrospectively analyzed. All
      patients had oligometastatic (93%) or oligoprogressive (7%) disease. Primary
      cancer diagnoses were 15 ovarian, 8 endometrial, 2 cervical, 2 vaginal, and 1
      uterine carcinosarcoma. Treatment was delivered using a median of 5 fractions to
      a median total dose of 40 Gy. Targets were grouped by treatment site and assessed
      for response using Response Evaluation Criteria in Solid Tumors v1.1. Mean
      biologically effective dose and pre-SABR tumor size were compared with response.
      Progression-free survival (PFS) was determined using Kaplan-Meier analysis, and
      toxicity outcomes were graded using Common Terminology Criteria for Adverse
      Events version 4.03. RESULTS: Median follow-up was 12.8 months. Target locations
      were 17% liver, 21% lung, 17% paraaortic node, 26% other node, and 19% pelvic
      soft tissue. After treatment, 34% of targets were stable (SD), 32% had a partial
      response (PR), 17% had a complete response (CR), and 17% had progressive disease
      (PD). No failures occurred in lung or nodal targets. Mean +/- standard deviation
      pre-SABR tumor diameter was 24 +/- 22 mm. There was a significant difference in
      mean size between lesions that had a favorable (SD, PR, and CR) versus
      unfavorable response (PD) (17.2 vs 57.6 mm, P = 0.0044). Lesions that responded
      favorably were also more likely to have received a higher biologically effective
      dose (79.0 vs 59.6 Gy, P = 0.027). Median PFS was 10.8 months, and 1 patient
      experienced grade 3 toxicity. CONCLUSIONS: The SABR is a safe and effective local
      treatment modality in patients with oligometastatic gynecological disease.
      Distant progression remains the primary mode of failure in this patient
      population. In carefully selected patients, a combination of systemic treatment
      and SABR may offer long-term PFS.

PMID- 27870703
TI  - Correlation of Collagen Triple Helix Repeat Containing 1 Overexpression With
      Lymph Node and Peritoneal Metastasis in Epithelial Ovarian Cancer.
AB  - OBJECTIVE: This study aimed to reveal whether collagen triple helix repeat
      containing 1 (CTHRC1) was a predictor of peritoneal and lymph node metastases in
      epithelial ovarian cancer, which had not been researched by others previously.
      MATERIALS AND METHODS: Western blot analysis showed that dramatic overexpression
      of CTHRC1 could be seen in most metastatic tissues. Univariate and multivariate
      logistic regression analyses demonstrated that overexpression of CTHRC1 was
      linked with peritoneal dissemination and lymph node metastasis in epithelial
      ovarian cancer. RESULTS: The negative and sensitivity-predictive values of CTHRC1
      staining were excellent for both lymph node and peritoneal metastases. The odds
      ratio of high versus low staining for peritoneal dissemination was 2.250 (95%
      confidence interval, 1.126-4.496), and that for lymph node metastasis was 13.102
      (95% confidence interval, 6.036-28.439). CONCLUSIONS: Collagen triple helix
      repeat containing 1 may potentially be used as a predictive marker of clinical
      progression in ovarian cancer either alone or in combination with other markers.

PMID- 27870705
TI  - Clinical Study on Female Genital Tract Rhabdomyosarcoma in Childhood: Changes
      During 20 Years in One Center.
AB  - OBJECTIVE: Rhabdomyosarcoma (RMS) is a rare tumor in girls. We intend to analyze
      the clinical feature, therapeutic effect, and prognosis of pediatric and
      adolescent RMS of the female genitourinary tract. METHODS: Pediatric or
      adolescent patients with female genital tract RMS in 1 tertiary hospital from
      1995 to 2015 were retrospectively reviewed. The medical records were collected,
      including general information, tumor primary site, stage, histology, treatments,
      adverse effects, and survival outcomes. RESULTS: There were 8 girls with genital
      tract tumor in 403 patients with RMS during 20 years in 1 hospital: 5 originated
      in the vagina, 2 in the cervix, and 1 in the pelvis. Except for the patient with
      pelvic RMS who was diagnosed after acute abdominal pain, all the other patients
      presented with polypoid masses protruding from the vagina accompanied by
      mucosanguineous discharge. Mean age of patients at diagnosis was 5.4 years (8
      months-14 years). Patients were categorized by using clinical group and TNM
      classification of malignant tumours staging system, 7 with stage I and 1 with
      stage II; none of them were classified to a higher stage. Histologically, all RMS
      were embryonal tumors with 3 botryoid variants. Patients were treated with
      surgery and adjuvant chemotherapy during which 6 patients developed fourth degree
      myelosuppression. All patients achieved complete remission. Two patients with
      vaginal RMS and the patient with pelvic RMS experienced tumor relapse and 2
      patients died. CONCLUSIONS: Rhabdomyosarcoma is a rare malignant sarcoma with a
      higher incidence in children and adolescents. Tumor sites are strongly associated
      with age at diagnosis. After combined therapy with local excision and
      chemotherapy, most patients can achieve a good prognosis. The prognosis is highly
      correlated with tumor site and histologic type.

PMID- 27870706
TI  - Evaluation of a Validated Biomarker Test in Combination With a Symptom Index to
      Predict Ovarian Malignancy.
AB  - OBJECTIVE: This study aimed to evaluate the predictive ability of a multivariate
      biomarker test in combination with a symptom index (SI) to identify ovarian
      cancer in a cohort of women planning to undergo surgery for a pelvic mass.
      METHODS: This was a prospective study of patients seen at a tertiary care medical
      center. Following consent, patients completed an SI and preoperative serum was
      collected for a Food and Drug Administration-cleared multivariate biomarker test
      [multivariate index assay (MIA)]. Results for the SI and MIA were correlated with
      operative findings and surgical pathology. RESULTS: Of 218 patients enrolled, 124
      (56.9%) had benign disease and 94 (43.1%) had borderline tumors or carcinomas.
      Sixty-six patients had a primary ovarian or fallopian tube cancer. The median age
      of patients enrolled in this study was 54 years (interquartile range, 44-63
      years), of whom 148 (67.9%) were postmenopausal. More than a third (36.3%) of
      patients with benign masses was accurately identified as low risk by MIA and SI.
      The sensitivity and negative predictive value (NPV) of the SI relative to primary
      ovarian cancer was 87.9% (95% CI, 77.9%-93.7%) and 91.6% (95% CI, 84.3%-95.7%),
      respectively. The sensitivity and NPV of CA125 was 75.4% (95% CI, 63.7%-84.2%)
      and 86.4% (95% CI, 79.1%-91.5%), respectively, and the sensitivity and NPV of the
      MIA were 93.9% (95% CI, 85.4%-97.6%) and 94.5% (95% CI, 94.5%-100%),
      respectively. The overall sensitivity for the combination of MIA plus SI was 100%
      (66/66; 95% CI, 94.5%-100%), and specificity was 36.3% (45/124; 95% CI, 28.4%
      45.0%), with an NPV of 100% (95% CI, 92.1%-100%). CONCLUSIONS: The addition of a
      patient-reported SI, which captures subjective symptoms in an objective manner,
      improved the sensitivity of MIA across all stages and subtypes of ovarian cancer.

PMID- 27870707
TI  - Time Trends in Ovarian Cancer Survival in Estonia by Age and Stage.
AB  - OBJECTIVE: The objective of the study was to examine temporal trends in ovarian
      cancer (OC) survival in Estonia during 1995 to 2009 in relation to age and stage.
      MATERIALS AND METHODS: Estonian Cancer Registry data on all adult cases of
      primary OC diagnosed during 1995 to 2009 and followed up for vital status until
      2014 were used to estimate relative survival ratios (RSRs). Cohort analysis was
      used to estimate 1-, 2-, and 5-year RSRs for patients diagnosed in 1995 to 1999,
      2000 to 2004, and 2005 to 2009. Analysis was performed by age at diagnosis (<50;
      50-59; 60-69; 70+ years) and stage (International Federation of Gynecology and
      Obstetrics 1988). RESULTS: Among 2296 women included in the study, the age
      adjusted 5-year RSR improved from 27% in 1995 to 1999 to 38% in 2005 to 2009.
      Survival increase of 10% units from 1995 to 1999 to 2005 to 2009 was seen for
      women aged 50 to 59 and 60 to 69 years. Among younger and older women, the
      respective changes were smaller. In 1995 to 1999, the difference in survival
      between the youngest and oldest age groups was 41% units. This decreased over the
      study period to 37% units. From 1995 to 1999 to 2005 to 2009, the 5-year RSR
      increased from 82% to 91% for stage I patients; from 48% to 67% for stage II
      patients; from 25% to 35% for stage III patients; and from 11% to 16% for stage
      IV patients. CONCLUSIONS: The study showed an improvement of OC survival in
      Estonia in all age and stage groups, but particularly among younger women and
      those with early stage disease. Slower progress among older women is of great
      concern.

PMID- 27870708
TI  - Sarcopenia in Advanced Serous Ovarian Cancer.
AB  - OBJECTIVE: Cancer cachexia is a paraneoplastic syndrome comprising involuntary
      weight loss and muscle depletion (sarcopenia). Although weight loss has been
      associated with poor clinical outcome, there is only limited information on the
      prevalence and prognostic impact of sarcopenia in ovarian cancer so far. METHODS:
      Total skeletal muscle mass was determined by computed tomography image analysis
      of the third lumbar skeletal muscle cross-sectional area in 128 patients with
      advanced serous ovarian cancer. Longitudinal change of muscle mass was studied in
      209 consecutive computed tomography scans from 43 patients. Association with
      survival was determined using Cox proportional hazards model. RESULTS: The
      prevalence of sarcopenia at first diagnosis was 11% (12/105; 95% confidence
      interval [CI], 6%-20%). Sarcopenic patients had a significantly reduced
      progression-free (hazard ratio, 2.64; 95% CI, 1.24-5.64; P = 0.012) and overall
      survival (hazard ratio, 3.17; 95% CI, 1.29-7.80; P = 0.012). On multivariable
      analysis, these prognostic effects remained significant after adjustment for age,
      International Federation of Gynecology and Obstetrics stage, and postsurgical
      residual disease. Longitudinal analyses identified both patients with loss and
      gain of muscle mass. However, change in muscle mass over time was not associated
      with survival. CONCLUSIONS: Baseline sarcopenia is a prognostic factor in
      advanced serous ovarian cancer. Identification of sarcopenic patients and early
      enrollment in physical or nutritional education programs might thus be a feasible
      way to improve outcome and should be further evaluated in prospective clinical
      trials.

PMID- 27870709
TI  - Groin Recurrences in Node Negative Vulvar Cancer Patients After Sole Sentinel
      Lymph Node Dissection.
AB  - OBJECTIVE: This study aimed to evaluate the recurrence rates after sole sentinel
      dissection in vulvar cancer and describe characteristics of groin recurrences.
      METHODS: All vulvar cancer cases between 2008 and 2014 were reviewed. Inclusion
      criteria were restricted to lymph node-negative patients, sole sentinel lymph
      node dissection (SLND), and tumor diameter less than 4 cm. In all patients, Tc
      99m nanocolloid was used for preoperative SLN imaging. Regularly, planar
      lymphoscintigraphy and single-photon emission computed tomography with computed
      tomography were performed. Ultrastaging was routinely conducted on all negative
      lymph nodes. RESULTS: Of 140 vulvar cancer cases, 30 node-negative patients
      underwent sole SLND and met inclusion criteria. Keratinizing squamous cell
      carcinoma was determined in final histology in 20/30 (66.7%) patients and the
      mainly diagnosed tumor stage was pT1b (21/30, 70%). Three perioperative
      complications occurred. On average, 4.6 (1-9) SLNs were dissected per patient and
      2.5 (1-6) per each groin, respectively. During a median follow-up of 43.5 (4-75)
      months, 5/30 (16.7%; 95% confidence interval, 7.3%-33.6%) local recurrences
      occurred. In addition, 2/30 (6.6%; 95% confidence interval, 1.9%-21.3%) groin
      recurrences were identified within a period of 12 months after the primary
      surgery. Both patients had large (>2 cm) midline tumors. Despite surgical as well
      as adjuvant treatment of the recurrent disease, both patients with groin
      recurrences died. CONCLUSIONS: Sentinel lymph node dissection is a safe and
      feasible alternative in early vulvar cancer. But false-negative sentinel carry a
      high risk of mostly fatal groin recurrences. Especially, midline tumors larger
      than 2 cm have to be treated with caution, because they are mostly found in cases
      with groin recurrences after sole SLND.

PMID- 27870710
TI  - Histopathology Discrepancy of Preoperative Endometrial Sampling and Final
      Specimen: How Does This Influence Selective Lymph Node Dissection?
AB  - OBJECTIVE: Preoperative histology is a major component in the perioperative
      selective lymph node (LN) dissection decision process. Discrepancy between
      preoperative endometrial sampling and final specimen histopathology is generally
      accepted. The goals of this project are to determine if discrepancy of
      histopathology is associated with alteration of adjuvant treatment or outcome.
      MATERIALS AND METHODS: We performed a retrospective cross-sectional analysis of
      all patients undergoing surgery for endometrial cancer at a single institution
      from 2010 to 2014. All patients had preoperative endometrial sampling.
      Histopathology discrepancy was evaluated for potential in variation of
      perioperative LN dissection. Criteria for not performing LN dissection was
      defined as preoperative endometrioid histology, grade 1 or 2 lesion, myometrial
      invasion of 50% or less, and primary tumor diameter 2 cm or less. RESULTS: A
      total of 352 patients were identified; 44 were excluded because of no
      preoperative pathology or no residual disease on final pathology. Discrepancy of
      histopathology was noted in 64/308 (20.8%; 95% confidence interval [CI], 16.2%
      25.3%) patients. Preoperative endometrioid histology was noted in 272 patients,
      and 17/272 (6.3%; 95% CI, 3.4%-9.1%) had preoperative sampling reviewed as a
      grade 1 or 2 endometrioid lesion and final specimen was upgraded to grade 3.
      Downstaging occurred in 3/272 (1.1%; 95% CI, 0%-2.3%) patients with preoperative
      grade 3 lesion and final specimen demonstrated grade 1 or 2 disease. All 3
      patients' primary tumor diameter was greater than 2 cm and therefore received LN
      dissection. Histopathological discrepancy that would alter perioperative LN
      dissection decision based on the aforementioned criteria occurred in 2/272 (0.7%;
      95% CI, 0%-1.8%). CONCLUSIONS: Despite a 20% discrepancy of preoperative and
      postoperative histopathology, discrepancy that would alter a perioperative
      decision for LN dissection occurs in only 0.7% of cases in this retrospective
      single-institutional experience. Myometrial invasion and tumor size may be more
      influential than histology in LN selection criteria.

PMID- 27870711
TI  - The Effect of Metformin on Oncological Outcomes in Patients With Cervical Cancer
      With Type 2 Diabetes Mellitus.
AB  - OBJECTIVE: The aim of this study was to evaluate any association between
      metformin use and oncological outcomes of cervical cancer in patients with type 2
      diabetes mellitus (DM). METHODS: We retrospectively identified 248 patients with
      cervical cancer with type 2 DM who received primary treatment between 2004 and
      2015. The clinicopathological characteristics and oncological outcomes were
      collected and analyzed. The patients were then separated into metformin use (n =
      118) or non-metformin use (n = 130) groups. RESULTS: With a median follow-up of
      2.85 years, patients who were given metformin had lower recurrence rate than
      patients who did not receive metformin (P = 0.011). The 5-year disease-free
      survival (DFS) and overall survival (OS) were 81.55% and 93.27% in the metformin
      use group, and 65.06% and 86.82% for the non-metformin use group, respectively.
      In multivariate analysis, non-metformin use (hazard ratio [HR], 1.89; P = 0.037),
      baseline hypertension (HR, 2.52; P = 0.005), and stage (HR for stage II vs I,
      3.48; HR for stage III vs I, 6.45; P = 0.01) were independent adverse prognostic
      factors for DFS, whereas the statistically significant independent prognostic
      factors for OS were age (HR for age >65 vs <=50, 3.86; P = 0.044) and stage (HR
      for stage III-IVA vs I-II, 3.45; P = 0.007). CONCLUSIONS: Our findings
      demonstrate that metformin use is associated with improved DFS, but not in OS in
      patients with cervical cancer with type 2 DM. Further large-scale and long-term
      follow-up studies are warranted to confirm the antitumor effects of metformin.

PMID- 27870713
TI  - The Frequency of Unplanned Rehospitalization and Associated Factors in
      Gyneoncology Patients: A Retrospective Study.
AB  - OBJECTIVE: In this study, we aim to analyze rate and associated factors with
      unplanned rehospitalization in gynecological cancer patients. MATERIALS AND
      METHODS: The electronic database query (2007 to 2014) was used to evaluate
      rehospitalization rates within 90 days of index admission in patients with
      gynecological cancer. Multivariable logistic regression was used to identify
      factors associated with rehospitalization. RESULTS: Mean patient age was 59.05 +/
      11.96 years (minimum, 32 years; maximum, 85 years). A total of 152 patients'
      data were evaluated. Seventy-three patients (48.0%) were rehospitalized within 90
      days of discharge. The median length of index hospital stay (from 3 to 34 days)
      was 8.90 +/- 6.03 days. The most common rehospitalization causes includes pain
      (24.6%), recurrence (21.9%), ascites (13.7%), surgical site infection (12.3%),
      acute reoperation (9.6%), thromboembolism (8.2%), renal failure (5.5%),
      ileus/obstruction (2.7%), and lymphedema (1.4%). In multivariable logistic
      regression model, difference was found between history of operation, receive
      chemotherapy, development of the complication during hospitalization
      comorbidities as well as multiparity variables, and rehospitalization (P < 0.05).
      CONCLUSIONS: Unplanned rehospitalization after discharge for gynecological cancer
      is common with significant associated risk factors and patient outcomes.
      Integrated multidisciplinary health care strategies, such as safe transition,
      communication, patient and family education, accurate medication reconciliation,
      and short-interval outpatient follow-up may help to prevent rehospitalization
      after discharge and improve patient outcomes.

PMID- 27870712
TI  - A Phase 2, Randomized, Open-Label Study of Irosustat Versus Megestrol Acetate in
      Advanced Endometrial Cancer.
AB  - OBJECTIVE: Advanced/metastatic or recurrent endometrial cancer has a poor
      prognosis. Malignant endometrial tissue has high steroid sulphatase (STS)
      activity. The aim of this study was to evaluate STS as a therapeutic target in
      patients with endometrial cancer. METHODS: This was a phase 2, multicenter,
      international, open-label, randomized (1:1), 2-arm study of the STS inhibitor
      oral irosustat 40 mg/d versus oral megestrol acetate 160 mg/d in women with
      advanced/metastatic or recurrent estrogen receptor-positive endometrial cancer.
      The primary end point was the proportion of patients without progression or death
      6 months after start of treatment. Secondary end points included progression-free
      survival, time to progression, overall survival, and safety. RESULTS: Seventy-one
      patients were treated (36 with irosustat, 35 with megestrol acetate). The study
      was prematurely stopped after futility analysis. Overall, 36.1% and 54.1% of
      patients receiving irosustat or megestrol acetate had not progressed or died at 6
      months, respectively. There were no statistically significant differences between
      irosustat and megestrol acetate in response and overall survival rates. Irosustat
      patients had a median progression-free survival of 16 weeks (90% confidence
      interval, 9.0-31.4) versus 40 weeks (90% confidence interval, 16.3-64.0) in
      megestrol acetate patients. Treatment-related adverse events occurred in 20
      (55.6%) and 13 (37.1%) patients receiving irosustat or megestrol, respectively.
      Most adverse events in both groups were grade 1 or 2. CONCLUSIONS: Although
      irosustat monotherapy did not attain a level of activity sufficient for further
      development in patients with advanced/recurrent endometrial cancer, this study
      confirms the activity of hormonal treatment (megestrol acetate) for this
      indication.

PMID- 27870714
TI  - Robotic-Assisted Video Endoscopic Inguinal Lymphadenectomy in Carcinoma Vulva:
      Our Experiences and Intermediate Results.
AB  - OBJECTIVES: To describe the technique of robotic-assisted video endoscopic
      inguinal lymphadenectomy (R-VEIL) in patients with carcinoma vulva and discuss
      the advantages of the technique and oncological outcome. METHODS: Twelve patients
      of squamous cell cancer of vulva underwent 22 R-VEIL procedures from February
      2011 to February 2015. Their preoperative, intraoperative, and postoperative data
      were retrospectively analysed. RESULTS: The mean age of patients was 61 years
      (range, 32-78 years). The mean operative time was 69.3 minutes (range, 45-95
      minutes). The mean blood loss was 30 mL (range, 15-50 mL). No intraoperative
      complication was observed. The mean drain output was 119 mL (range, 50-250 mL),
      and the drains were removed at a mean of 13.9 days (range, 8-38 days). The
      average number of superficial and deep inguinofemoral lymph nodes retrieved was
      11 (range, 4-26). Two patients had positive lymph nodes on histopathology
      (16.67%). Postoperative complications were lymphocele (6 groins), chronic lower
      limb lymphedema (6 cases), prolonged lymphorrhea (1 groin), and cellulitis (2
      groins). Over a follow-up period ranging from 7 to 67 months, 1 patient developed
      recurrence in the inguinal nodes and died 7 months after the recurrence.
      CONCLUSIONS: The R-VEIL allows the removal of inguinal lymph nodes within the
      same limits as the open procedure for inguinal lymph node dissection and has a
      potential to reduce the surgical morbidity associated with the open procedure.
      Long-term oncological results are not available though our initial results appear
      promising. Prospective multi-institutional studies are required to prove its
      efficacy over open inguinal lymph node dissection.

PMID- 27870716
TI  - The Big 4: Using Primary Prevention to Drive Population Health.

PMID- 27870715
TI  - Posttranscriptional Control of PD-L1 Expression by 17beta-Estradiol via PI3K/Akt
      Signaling Pathway in ERalpha-Positive Cancer Cell Lines.
AB  - OBJECTIVE: Estrogen is a well-known oncogenic driver in endometrial (ECs) and
      breast cancers (BCs). Programmed cell death protein 1 (PD-1) and its ligands PD-1
      Ligand 1 (PD-L1) and PD-L2 have been shown to mediate immune evasion of the tumor
      cells. The purpose of the present study was to assess the effects of estrogen on
      PD-L1 and PD-L2 expression in EC and BC cell lines. METHODS: 17beta-Estradiol
      (E2)-induced expression of PD-L1 and PD-L2 and possible signaling pathway were
      investigated in EC and BC cells. Coculture of T cells and cancer cells with E2
      stimulation was performed to assess the functions of T cells. RESULTS: We found
      that E2 increased expression of PD-L1, but not PD-L2, protein via activation of
      phosphoinositide 3-kinase (PI3K)/Akt pathway in Ishikawa and Michigan Cancer
      Foundation-7 (MCF-7) cells. Phosphoinositide 3-kinase and Akt inhibitors could
      block E2's effects. 17beta-Estradiol did not increase PD-L1 mRNA transcription,
      but stabilized PD-L1 mRNA. 17beta-Estradiol's effects were only observed in
      estrogen receptor alpha (ERalpha)-positive Ishikawa and MCF-7 cells, but not in
      ERalpha-negative MDA-MB-231 cells. Coculture of Ishikawa or MCF-7 cells with T
      cells inhibited expression of interferon-gamma and interleukin-2 and increased
      BCL-2-interacting mediator of cell death expression in the presence of E2.
      CONCLUSIONS: This study provides the first evidence that estrogen upregulates PD
      L1 protein expression in ERalpha-positive EC and BC cells to suppress immune
      functions of T cells in the tumor microenvironment, demonstrating a new mechanism
      of how estrogen drives cancer progression.

PMID- 27870717
TI  - An International Comparison of the Instigation and Design of Health Registers in
      the Epidemiological Response to Major Environmental Health Incidents.
AB  - CONTEXT: Epidemiological preparedness is vital in providing relevant,
      transparent, and timely intelligence for the management, mitigation, and
      prevention of public health impacts following major environmental health
      incidents. A register is a set of records containing systematically collected,
      standardized data about individual people. Planning for a register of people
      affected by or exposed to an incident is one of the evolving tools in the public
      health preparedness and response arsenal. OBJECTIVE: We compared and contrasted
      the instigation and design of health registers in the epidemiological response to
      major environmental health incidents in England, France, Italy, the Netherlands,
      and the United States. DESIGN: Consultation with experts from the 5 nations,
      supplemented with a review of gray and peer-reviewed scientific literature to
      identify examples where registers have been used. SETTING: Populations affected
      by or at risk from major environmental health incidents in England, France,
      Italy, the Netherlands, and the United States. METHODS: Nations were compared
      with respect to the (1) types of major incidents in their remit for considering a
      register; (2) arrangements for triggering a register; (3) approaches to design of
      register; (4) arrangements for register implementation; (5) uses of registers;
      and (6) examples of follow-up studies. RESULTS: Health registers have played a
      key role in the effective public health response to major environmental
      incidents, including sudden chemical, biological, radiological, or nuclear, as
      well as natural, more prolonged incidents. Value has been demonstrated in the
      early and rapid deployment of health registers, enabling the capture of a
      representative population. CONCLUSION: The decision to establish a health
      register must ideally be confirmed immediately or soon after the incident using a
      set of agreed criteria. The establishment of protocols for the instigation,
      design, and implementation of health registers is recommended as part of
      preparedness activities. Key stakeholders must be aware of the importance of, and
      protocols for, establishing a register.Agencies will find value in preparing and
      implementing registers as part of an effective public health response to major
      environmental incidents, including sudden chemical, biological, radiological, or
      nuclear incidents, as well as natural, more prolonged incidents.

PMID- 27870719
TI  - Public Health Leadership and Management in the Era of Public Health 3.0.

PMID- 27870718
TI  - Self-reported Preparedness to Respond to Mass Fatality Incidents in 38 State
      Health Departments.
AB  - CONTEXT: Public health departments play an important role in the preparation and
      response to mass fatality incidents (MFIs). OBJECTIVE: To describe MFI response
      capabilities of US state health departments. DESIGN: The data are part of a
      multisector cross-sectional study aimed at 5 sectors that comprise the US mass
      fatality infrastructure. Data were collected over a 6-week period via a self
      administered, anonymous Web-based survey. SETTING: In 2014, a link to the survey
      was distributed via e-mail to health departments in 50 states and the District of
      Columbia. PARTICIPANTS: State health department representatives responsible for
      their state's MFI plans. MEASURES: Preparedness was assessed using 3 newly
      developed metrics: organizational capabilities (n = 19 items); operational
      capabilities (n = 19 items); and resource-sharing capabilities (n = 13 items).
      RESULTS: Response rate was 75% (n = 38). Among 38 responses, 37 rated their
      workplace moderately or well prepared; 45% reported MFI training, but only 30%
      reported training on MFI with hazardous contaminants; 58% estimated high levels
      of staff willingness to respond, but that dropped to 40% if MFIs involved
      hazardous contaminants; and 84% reported a need for more training. On average,
      76% of operational capabilities were present. Resource sharing was most prevalent
      with state Office of Emergency Management but less evident with faith-based
      organizations and agencies within the medical examiner sector. CONCLUSION:
      Overall response capability was adequate, with gaps found in capabilities where
      public health shares responsibility with other sectors. Collaborative training
      with other sectors is critical to ensure optimal response to future MFIs, but
      recent funding cuts in public health preparedness may adversely impact this
      critical preparedness element. In order for the sector to effectively meet its
      public health MFI responsibilities as delineated in the National Response
      Framework, resources to support training and other elements of preparedness must
      be maintained.

PMID- 27870720
TI  - Strengthening the Capacity of Local Health Departments to Reduce Exposure to
      Electronic Nicotine Delivery Systems.

PMID- 27870721
TI  - Differences in Health Care Needs, Health Care Utilization, and Health Care
      Outcomes Among Children With Special Health Care Needs in Ohio: A Comparative
      Analysis Between Medicaid and Private Insurance.
AB  - OBJECTIVE: This study explores comparative differentials in health care needs,
      health care utilization, and health status between Medicaid and private/employer
      sponsored insurance (ESI) among a statewide population of children with special
      health care needs (CSHCN) in Ohio. METHODS: We used data from the 2012 Ohio
      Medicaid Assessment Survey to examine CSHCN's health care needs, utilization,
      status, and health outcomes by insurance type. Adjusted multivariable logistic
      regression models were used to explore associations between public and private
      health insurance, as well as the utilization and health outcome variables.
      RESULTS: Bivariate analyses indicate that the Medicaid population had higher care
      coordination needs (odds ratio [OR] = 1.6; 95% confidence interval [CI], 1.1-2.2)
      as well as need for mental/educational health care services (OR = 1.5; 95% CI;
      1.1-2.0). They also reported higher unmet dental care needs (OR = 2.2; 95% CI,
      1.2-4.0), higher emergency department (ED) utilization (OR = 2.3; 95% CI, 1.7
      3.2), and worse overall health (OR = 0.6; 95% CI, 0.4-0.7), oral health (OR =
      0.4; 95% CI, 0.3-0.5), and vision health (OR = 0.4; 95% CI, 0.2-0.6). After
      controlling for demographic variables, CSHCN with Medicaid insurance coverage
      were more likely to need mental health and education services (adjusted odds
      ratio [AOR] = 1.8; 95% CI; 1.2-2.6), had significantly more ED visits (AOR = 2.3;
      95% CI, 1.5-3.5), and were less likely to have excellent overall health (AOR =
      0.64; 95% CI, 0.4-0.9), oral health (AOR = 0.43; 95% CI, 0.3-0.7), and vision
      health (AOR = 0.38; 95% CI, 0.2-0.6) than those with private insurance/ESI.
      CONCLUSION: The CSHCN population is a highly vulnerable population. While Ohio's
      Medicaid provides greater coverage to CSHCN, disparities continue to exist within
      access and services that Medicaid provides versus the ones provided by private
      insurance/ESI.

PMID- 27870722
TI  - A Qualitative Study of Symptom Experiences of Women With Acute Coronary Syndrome.
AB  - BACKGROUND: Most studies show that women with symptoms of acute coronary syndrome
      (ACS) delay seeking care longer than men do. Contributing factors include women
      being more likely to experience diverse symptoms, to experience symptoms that do
      not match preexisting symptom expectations, to interpret symptoms as noncardiac,
      and to minimize symptoms until they become incapacitating. OBJECTIVE: The aim of
      the study is to identify factors influencing women's ability to recognize and
      accurately interpret symptoms of suspected ACS. METHODS: This qualitative study
      used in-depth interviews with 18 women diagnosed with ACS to determine how they
      recognized, interpreted, and acted on symptoms. An interview guide developed from
      the author's initial research was used to provide structure for the process.
      RESULTS: All of the women went through a process of recognizing and interpreting
      their symptoms. Eight women had symptoms arise abruptly. Most of these women
      recognized a change immediately, "knew" to go for treatment, and did so quickly.
      Three women had vague symptoms that started slowly, converting unexpectedly to
      intense symptoms prompting them to seek care urgently. The remaining 7 women had
      evolving symptoms, were more likely to interpret symptoms as unrelated to their
      heart, and avoided disclosing symptoms to others. Despite recognizing that the
      situation may be serious, women with evolving symptoms adopted a wait-and-see
      approach. CONCLUSION: Women with less severe, intermittent, or evolving symptoms
      are at increased risk for delayed presentation, diagnosis, and treatment for ACS.
      These women should be targeted for educational and behavioral interventions.

PMID- 27870724
TI  - The Effects of Dietary Calcium Supplements Alone or With Vitamin D on Cholesterol
      Metabolism: A Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Evidence supports the role of lifestyle interventions as a primary
      intervention strategy among individuals with dyslipidemia. The role of
      micronutrients, and calcium in particular, on cholesterol metabolism is not clear
      and warrants further investigation. OBJECTIVE: The aim of this study is to
      conduct a meta-analysis of controlled clinical trials that have examined the
      effects of calcium supplements on blood lipids among adults. METHODS: MEDLINE,
      EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials
      databases were searched up to March 2016 for calcium supplements clinical trials.
      Other trials were selected from searching bibliography of reviews, meta-analysis,
      and included trials. Clinical trials with random allocation to calcium
      supplementation or calcium plus vitamin D supplementation, or control were
      selected. Data collected included study design, participant characteristics,
      information of the intervention, and outcomes. Data synthesis was conducted using
      random effect models. RESULTS: A total of 22 trials, representing 4071
      participants, met the eligibility criteria. Compared with control group, calcium
      supplements significantly reduced low-density lipoprotein cholesterol level by 
      0.12 mmol/L (95% confidence interval, -0.22 to -0.02) and increased high-density
      lipoprotein cholesterol level by 0.05 mmol/L (95% confidence interval, 0.00 to
      0.10). Subgroup analyses revealed that the associations were consistent across
      study duration and vitamin D cosupplementation status. CONCLUSIONS: Calcium
      supplementation has beneficial effect on blood lipids. Such supplements may be
      useful as a nonpharmaceutical strategy in cholesterol control.

PMID- 27870726
TI  - Melanocytic Nevi of Special Sites.
AB  - Melanocytic nevi located on specific regions of the body can demonstrate unusual
      histopathological features such as asymmetry, irregular nesting patterns,
      pagetoid spread, cytologic atypia, and rarely, mitotic activity. However, despite
      these features that may raise concern for malignant melanoma, these lesions
      follow a benign clinical course and do not require intervention. Also known as
      nevi of special sites or nevi with site-related atypia, these melanocytic nevi
      were initially described on acral sites and genitalia. Now, additional anatomical
      sites with known site-related atypia include the ear, conjunctivae, scalp,
      breast, flexural skin, legs, and back and shoulder. This continuing medical
      education article presents a review of the histopathological characteristics of
      special site nevi based on anatomic location. It is imperative for
      dermatologists, pathologists, and dermatopathologists to distinguish benign
      melanocytic nevi with site-related atypia from malignant melanoma to avoid
      unnecessary surgical intervention or treatment.

PMID- 27870723
TI  - Influence of Baseline Psychological Health on Muscle Pain During Atorvastatin
      Treatment.
AB  - BACKGROUND: 3-hydroxy-3-methylglutaryl coenzyme A reductase reductase inhibitors
      (statins) are generally well tolerated, with statin-associated muscle symptoms
      (SAMS) the most common side effect (~10%) seen in statin users. However, studies
      and clinical observations indicate that many of the self-reported SAMS appear to
      be nonspecific (ie, potentially not attributable to statins). OBJECTIVE: Mental
      health and well-being influence self-perception of pain, so we sought to assess
      the effect of baseline well-being and depression on the development of muscle
      pain with 6 months of atorvastatin 80 mg/d (ATORVA) or placebo in healthy, statin
      naive adults. METHODS: The Psychological General Well-being Index (n = 83) and
      Beck Depression Inventory (n = 55) questionnaires were administered at baseline
      in participants (aged 59.5 +/- 1.2 years) from the effect of Statins on Skeletal
      Muscle Function and Performance (STOMP) trial (NCT00609063). Muscle pain (Short
      Form McGill Pain Questionnaire [SF-MPQ]), pain that interferes with daily life
      (Brief Pain Inventory [BPI]), and pain severity (BPI) were then measured before,
      throughout, and after treatment. RESULTS: At baseline, there were no differences
      in well-being (Psychological General Well-being Index), depression (Beck
      Depression Inventory), or pain measures (SF-MPQ and BPI) (P values >= .05)
      between the placebo and ATORVA groups. Baseline well-being correlated negatively
      with baseline BPI pain severity (r = -0.290, P = .008). Baseline depression
      correlated with baseline pain (SF-MPQ; r = 0.314, P = .020). Baseline well-being
      and depression did not predict the change in pain severity or interference after
      6 months among the total sample or between groups (P values >= .05). CONCLUSION:
      Baseline well-being and depression were not significant predictors of pain after
      6 months of ATORVA (P values >= .05). Thus, they do not appear to increase the
      risk of SAMS in otherwise healthy adults.

PMID- 27870727
TI  - Solitary Annular Plaque on the Scrotum.

PMID- 27870728
TI  - Erythematous and Hyperpigmented Macules on the Feet.

PMID- 27870730
TI  - Cutaneous Sebaceous Lesions in a Patient With MUTYH-Associated Polyposis
      Mimicking Muir-Torre Syndrome.
AB  - A 76-year-old white male with a history of adenocarcinoma of the rectosigmoideum
      and multiple colonic polyps removed at the age of 38 and 39 years by an
      abdominoperitoneal amputation and total colectomy, respectively, presented with
      multiple whitish and yellowish papules on the face and a verrucous lesion on the
      trunk. The lesions were surgically removed during the next 3 years and a total of
      13 lesions were investigated histologically. The diagnoses included 11 sebaceous
      adenomas, 1 low-grade sebaceous carcinoma, and 1 squamous cell carcinoma. In some
      sebaceous lesions, squamous metaplasia, intratumoral heterogeneity, mucinous
      changes, and peritumoral lymphocytes as sometimes seen in sebaceous lesions in
      Muir-Torre syndrome were noted. Mutation analysis of the peripheral blood
      revealed a germline mutation c.692G>A,p.(Arg231His) in exon 9 and c.1145G>A,
      p.(Gly382Asp) in exon 13 of the MUTYH gene. A KRAS mutation G12C (c.34G>T,
      p.Gly12Cys) was detected in 1 sebaceous adenoma and a NRAS mutation Q61K
      (c.181C>A, p.Gln61Lys) was found in 2 other sebaceous adenomas. No germline
      mutations in MLH1, MSH2, MSH6 and PMS2 genes, no microsatellite instability, no
      aberrant methylation of MLH1 promoter, and no somatic mutations in MSH2 and MSH6
      were found. An identical MUTYH germline mutation was found in the patient's
      daughter. Despite striking clinicopathological similarities with Muir-Torre
      syndrome, the molecular biologic testing confirmed the final diagnosis of MUTYH
      associated polyposis.

PMID- 27870729
TI  - Aggressive Digital Papillary Adenocarcinoma With Multiple Organ Metastases: A
      Case Report and Review of the Literature.
AB  - Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland neoplasm
      with a high recurrence rate and metastatic potential. In this study, the authors
      describe a case that originally appeared to benign spiradenoma, but took an
      ominous course eventually resulting in the diagnosis of ADPA. A 73-year-old woman
      developed a gradually growing nodule on the second toe of her left foot, which
      she had first noticed 4 years previously. An excisional biopsy was performed
      followed by histological examination. The authors initially considered the tumor
      to be a benign spiradenoma and did not perform reexcision. However, she
      experienced local recurrence 24 months later, and multiple pulmonary metastasis
      31 months later. On histological examination, both the primary and locally
      recurrent tumors were found to be composed of discrete and well-circumscribed
      solid nodules, lacking cystic space. All tumors (the primary tumor, locally
      recurrent tumor, and lung metastases) presented with a pattern of fused back-to
      back tubular structures and myoepithelial differentiation confirmed by
      immunohistochemical examination. On the basis of these findings, the authors
      finally diagnosed ADPA with multiple pulmonary metastases. The patient underwent
      chemotherapy, but died of disease 49 months later. This case highlights the
      importance of high clinical suspicion of ADPA when digital lesions present.

PMID- 27870731
TI  - Solitary Annular Plaque on the Scrotum.

PMID- 27870732
TI  - Erythematous and Hyperpigmented Macules on the Feet.

PMID- 27870733
TI  - Cutaneous Metastatic Melanoma Resembling a Halo Nevus, in the Setting of PD-1
      Inhibition.
AB  - Malignant melanoma is a common source of cutaneous metastases and can
      occasionally adopt a histological appearance which mimics a primary melanocytic
      lesion, either benign or malignant. The authors describe a case of new cutaneous
      deposits of metastatic melanoma in a 70-year-old woman with a prominent admixed
      lymphocytic infiltrate, imparting a striking resemblance to a halo nevus. The
      authors believe this appearance was a direct reflection of treatment with
      pembrolizumab, a humanized antibody against the immune checkpoint inhibitor
      programmed death-1. With increasing use of immune-modulating drugs, this
      potential histological mimic may be seen more frequently in the future.

PMID- 27870734
TI  - Incremental Value of Preoperative Copeptin for Predicting Myocardial Injury.
AB  - BACKGROUND: Copeptin, a novel marker of endogenous stress, has shown diagnostic
      and prognostic value in nonsurgical patients with a suspected coronary event. We
      aimed to assess the incremental value of copeptin in addition to established
      preoperative risk indices to predict the occurrence of postoperative myocardial
      injury. METHODS: This secondary analysis of prospectively collected data included
      adults undergoing noncardiac surgery with risk factors for adverse perioperative
      cardiac events based on preoperative risk stratification. We examined
      preoperative copeptin in patients without elevated preoperative troponin and its
      association with myocardial injury by receiver operator characteristic curves,
      logistic regression, and net reassignment indices. RESULTS: Of the 190 patients
      included, 33 (17.4%) experienced myocardial injury within 48 hours, and 17 (8.9%)
      experienced cardiac death and/or major adverse cardiac events within the first
      postoperative year. Preoperative copeptin showed an area under the receiver
      operator characteristic curve of .66 (95% confidence interval, .55-.76) for
      myocardial injury and an optimal cutoff of 9.6 pmol/L. This cutoff was an
      independent predictor of myocardial injury, with an odds ratio of 4.67 (95%
      confidence interval, 2.06-11.19) when adjusted for age, sex, and the revised
      cardiac risk index. The net reassignment improvement for myocardial injury was
      between 39% and 50% for both events and nonevents when adding copeptin to
      established preoperative risk indices. No significant difference in major adverse
      cardiac event and/or cardiac death was observed. CONCLUSIONS: Copeptin (>=9.6
      pmol/L) was associated with significantly higher rates of myocardial injury and
      improved risk stratification in patients scheduled for noncardiac surgery with
      nonelevated preoperative troponin.

PMID- 27870735
TI  - Combination of 5-HT3 Antagonist and Dexamethasone Is Superior to 5-HT3 Antagonist
      Alone for PONV Prophylaxis After Laparoscopic Surgeries: A Meta-analysis.
AB  - INTRODUCTION: 5-Hydroxytryptamine type 3 (5-HT3) receptor antagonists are the
      most commonly used drugs for postoperative nausea vomiting (PONV) prophylaxis.
      Dexamethasone is another antiemetic with proven efficacy in reducing PONV. The
      aim of this study was to conduct a systematic review and meta-analysis of
      randomized controlled trials (RCTs) to compare the combination of dexamethasone
      and 5-HT3 antagonist versus a 5-HT3 antagonist alone as prophylaxis of PONV in
      laparoscopic surgical patients. METHODS: PubMed, PubMed Central, and CENTRAL
      databases were searched to identify those randomized trials that compared a 5-HT3
      antagonist with the 5-HT3 antagonist and dexamethasone combination for PONV
      prophylaxis after laparoscopic surgeries. RESULTS: Data from 17 RCTs that
      evaluated 1402 patients were included. Results from our meta-analysis show that
      the combination of dexamethasone and a 5-HT3 receptor antagonist is more
      effective in preventing PONV than the 5-HT3 antagonist alone (odds ratio 0.38,
      95% confidence interval [CI] 0.27-0.54; number needed to treat = 6.6), with no
      statistical heterogeneity (I = 0) among studies. The need for rescue antiemetic
      is also decreased in patients receiving the combination (odds ratio 0.21, 99% CI
      0.10-0.46; number needed to treat = 6), although data are insufficient to detect
      any significant difference in incidence of adverse effects. In addition, patients
      in the combination group complained of less pain after 24 hours (Weighted Mean
      Difference -0.67, 99% CI -1.27 to -0.08). CONCLUSION: Combination of a 5-HT3
      receptor antagonist and dexamethasone is significantly more effective than 5-HT3
      antagonist alone in preventing PONV after laparoscopic surgeries, with possible
      improvement in postoperative analgesia.

PMID- 27870736
TI  - Lidocaine Administration Controls MicroRNAs Alterations Observed After Lung
      Ischemia-Reperfusion Injury.
AB  - BACKGROUND: Ischemia-reperfusion injury (IRI) is associated with morbidity and
      mortality. MicroRNAs (miRNAs) have emerged as regulators of IRI, and they are
      involved in the pathogenesis of organ rejection. Lidocaine has proven anti
      inflammatory activity in several tissues but its modulation of miRNAs has not
      been investigated. This work aims to investigate the involvement of miRNAs in
      lung IRI in a lung auto-transplantation model and to investigate the effect of
      lidocaine. METHODS: Three groups (sham, control, and Lidocaine), each comprising
      6 pigs, underwent a lung autotransplantation. All groups received the same
      anesthesia. In addition, animals of lidocaine group received a continuous
      intravenous administration of lidocaine (1.5 mg/kg/h) during surgery. Lung
      biopsies were taken before pulmonary artery clamp, before reperfusion, 30 minutes
      postreperfusion (Rp-30), and 60 minutes postreperfusion (Rp-60). Samples were
      analyzed for different miRNAs (miR-122, miR-145, miR-146a, miR-182, miR-107, miR
      192, miR-16, miR-21, miR-126, miR-127, miR142-5p, miR152, miR155, miR-223, and
      let7) via the use of reverse-transcription quantitative polymerase chain
      reaction. Results were normalized with miR-103. RESULTS: The expression of miR
      127 and miR-16 did not increase after IRI. Let-7d, miR-21, miR-107, miR-126, miR
      145, miR-146a, miR-182, and miR-192 significantly increased at the Rp-60 (control
      versus sham P < .001). miR-142-5p, miR-152, miR-155, and miR 223 significantly
      increased at the Rp-30 (control versus sham P < .001) and at the Rp-60 (control
      versus. sham P < .001). The administration of lidocaine was able to attenuate
      these alterations in a significant way (control versus Lidocaine P < .001).
      CONCLUSIONS: Lung IRI caused dysregulation miRNA. The administration of lidocaine
      reduced significantly miRNAs alterations.

PMID- 27870737
TI  - The Influence of Body Mass Index on Sensorimotor Block and Vasopressor
      Requirement During Spinal Anesthesia for Elective Cesarean Delivery.
AB  - BACKGROUND: It has been suggested that the dose requirement for spinal anesthesia
      (SA) is lower in obese patients for cesarean delivery (CD). In this prospective,
      observational, noninferiority study, we tested the hypothesis that obesity would
      not have a clinically important effect on vasopressor requirements or block
      height. METHODS: Two groups of 25 parturients, group O (body mass index [BMI] >40
      kg/m) and group N (BMI <32 kg/m) requiring elective CD were recruited. All
      patients received 10 mg intrathecal hyperbaric bupivacaine coadministered with 10
      MUg fentanyl. Dermatomal levels were assessed at 5 and 25 minutes after SA, and
      at completion of surgery, using light touch and cold sensation in response to
      ethyl chloride. The primary outcomes were phenylephrine requirement in the first
      30 minutes after SA, and maximum block height, measured by the sensation of touch
      and cold. Secondary outcomes were total phenylephrine dose required, changes in
      hand grip strength, and peak flow rate. RESULTS: There were no significant
      between-group differences in median block height as assessed by touch at 5 or 25
      minutes or by temperature at 5 minutes. At 25 minutes, there was a 2-dermatome
      difference in median block height for loss of temperature sensation between group
      O and group N (T2 vs T4, 95% confidence interval [CI] of the difference in
      medians 0-2 dermatomes). No blocks extended to cervical dermatomes. The median
      (range) phenylephrine dose for the first 30 minutes was 150 ug (0-900 ug), and
      100 ug (0-1250 ug) in group N and group O, respectively. The 95% CI for the
      difference between the 2 median doses was -150 ug to 100 ug. There were no
      differences in median percentage reductions in peak flow rate or median hand grip
      strength after SA. Mean surgical time was longer in group O than in group N (49.1
      vs 39.4 min, 95% CI difference 1.7-17.7 min). The mean time for recovery of touch
      sensation to T10 was longer in group O (152 vs 132 min, 95% CI difference 3.8
      36.2 min). No analgesic supplementation was required. CONCLUSION: Only a minor
      increase in block height as assessed by temperature occurred in group O at 25
      minutes. Vasopressor requirements during the first 30 minutes of SA were
      equivalent. Time for regression of SA block level was longer in the group O,
      which may be beneficial considering the longer surgical time. A dose of spinal
      bupivacaine 10 mg for single-shot SA should not be reduced in morbidly obese
      parturients.

PMID- 27870738
TI  - Persistent Pain After Cesarean Delivery and Vaginal Delivery: A Prospective
      Cohort Study.
AB  - BACKGROUND: Persistent pain after cesarean delivery and vaginal delivery has been
      the subject of only a few research articles. The primary outcome of our
      prospective study was the incidence of persistent pain and its association to
      mode of delivery. We also studied the nature and intensity of pain after
      delivery. METHODS: A questionnaire was distributed on postpartum day 2 to 1052
      women who had given birth vaginally and to 502 who had undergone cesarean
      delivery in a tertiary maternity hospital in Helsinki, Finland, in 2010. A second
      questionnaire was mailed to the women 1 year later. We recorded the women's
      health history, obstetric history and previous pain history, details of cesarean
      delivery or vaginal delivery, and description of pain, if present. RESULTS: The
      incidence of persistent pain at 1 year after delivery was greater after cesarean
      delivery (85/379 [22%]) than after vaginal delivery (58/713 [8%]: P < .001,
      relative risk 2.8, 95% confidence interval 2.0-3.8). Because of initial
      differences in the groups, we performed logistic regression analysis with
      persistent pain as a dependent factor that confirmed the mode of delivery as a
      predictor of persistent pain. The incidence of persistent pain graded as moderate
      or more severe (25/379 [7%] vs 25/713 [4%]: P = .022, relative risk 1.9, 95%
      confidence interval 1.1-3.2) was also greater after cesarean delivery than
      vaginal delivery. The incidence of persistent pain was significantly more common
      in women with a history of previous pain and among primiparous women in logistic
      regression analysis. The women with persistent pain had experienced more pain the
      day after cesarean delivery (P = .023) and during vaginal delivery (P = .030)
      than those who did not report persistent pain. Complications such as perineal
      trauma, episiotomy, vacuum extraction, endometritis, wound infection, or ante- or
      postpartum depression did not predispose women to persistent pain. Dyspareunia
      was reported by 41% of women after vaginal delivery and by 2% after cesarean
      delivery among women with persistent pain at 1 year. CONCLUSIONS: The incidence
      of persistent pain at 1 year is greater after cesarean delivery than after
      vaginal delivery. Pain shortly after cesarean delivery and during vaginal
      delivery correlated with persistent pain.

PMID- 27870739
TI  - Performance of the Angle Labor Pain Questionnaire During Initiation of Epidural
      Analgesia in Early Active Labor.
AB  - BACKGROUND: The Angle Labor Pain Questionnaire (A-LPQ) is a new, 22-item
      multidimensional psychometric questionnaire that measures the 5 most important
      dimensions of women's childbirth pain experiences using 5 subscales: The Enormity
      of the Pain, Fear/Anxiety, Uterine Contraction Pain, Birthing Pain, and Back
      Pain/Long Haul. Previous work showed that the A-LPQ has overall good psychometric
      properties and performance during early active labor in women without pain
      relief. The current study assessed the tool's sensitivity to change during
      initiation of labor epidural analgesia with the standardized response mean (SRM,
      primary outcome). METHODS: Two versions of the A-LPQ were administered once, in
      each of 2 test sessions, by the same trained interviewer during early active
      labor. The sequence of administration was randomized (ie, standard question order
      version [Test 1] followed by mixed version [Test 2] or vice versa). Test 1 was
      completed before epidural insertion; Test 2 commenced 20 to 30 minutes after the
      test dose. Providers assessed/treated pain independently of the study.
      Sensitivity to change was assessed using SRMs, Cohen's d, and paired t tests.
      Overall pain intensity was concurrently examined using Numeric Rating Scale and
      the Verbal Rating Scale (VRS); coping was assessed with the Pain Mastery Scale.
      Changes in pain were measured with the Patient Global Impression of Change Scale.
      Internal consistency was assessed with Cronbach's alpha. Concurrent validity with
      other tools was assessed using Spearman's rank correlation coefficient. RESULTS:
      A total of 51 complete datasets were analyzed. Most women reported moderate (63%,
      32/51) or severe (18%, 9/51) baseline pain on VRS scores during Test 1; 29%
      (15/51) reported mild pain, and 6% (3/51) reported moderate pain during Test 2.
      Approximately 90% (46/51) of women reported much or very much improved pain at
      the end of testing. Cronbach's alpha for A-LPQ summary scores was excellent
      (0.94) and ranged from 0.78 (acceptable) to 0.92 (excellent) for subscales (Test
      1). Large SRMs were found for A-LPQ summary scores (1.6, 95% CI: 1.2, 2.1) and
      all subscales except the Birthing Pain subscale (moderate, 0.60, 95% CI: 0.23,
      0.97). Significant (P < .001) differences were found between A-LPQ summary scores
      and between all subscales on paired t tests. Correlations between A-LPQ summary
      and Numeric Rating Scale scores (overall pain intensity) were strong (rho >
      0.73), correlations were moderate (rho > 0.5) with VRS scores and coping scores
      (rho > 0.67). CONCLUSIONS: Findings support A-LPQ use for measurement of women's
      childbirth pain experiences during initiation of labor epidural analgesia during
      early active labor. Combined with our previous work, they also support the use of
      the A-LPQ in late labor and at delivery.

PMID- 27870740
TI  - Patient Blood Management: An International Perspective.
AB  - This article describes practices in patient blood management (PBM) in 4 countries
      on different continents that may provide insights for anesthesiologists and other
      physicians working in global settings. The article has its foundation in the
      proceedings of a session at the 2014 AABB annual meeting during which
      international experts from England, Uganda, China, and Brazil presented the
      programs and implementation strategies in PBM developed in their respective
      countries. To systematize the review and enhance the comparability between these
      countries on different continents, authors were requested to respond to the same
      set of 6 key questions with respect to their country's PBM program(s).
      Considerable variation exists between these country regions that is driven both
      by differences in health contexts and by disparities in resources. Comparing PBM
      strategies from low-, middle-, and high-income countries, as described in this
      article, allows them to learn bidirectionally from one another and to work toward
      implementing innovative and preferably evidence-based strategies for improvement.
      Sharing and distributing knowledge from such programs will ultimately also
      improve transfusion outcomes and patient safety.

PMID- 27870741
TI  - Relationship Between Preoperative Anemia and In-Hospital Mortality in Children
      Undergoing Noncardiac Surgery.
AB  - BACKGROUND: The relationship between preoperative anemia and in-hospital
      mortality has not been investigated in the pediatric surgical population. We
      hypothesized that children with preoperative anemia undergoing noncardiac surgery
      may have an increased risk of in-hospital mortality. METHODS: We identified all
      children between 1 and 18 years of age with a recorded preoperative hematocrit
      (HCT) in the 2012, 2013, and 2014 American College of Surgeons National Surgical
      Quality Improvement Program (ACS NSQIP) pediatric databases. The endpoint was
      defined as the incidence of in-hospital mortality. Children with preoperative
      anemia were identified based on their preoperative HCT. Demographic and surgical
      characteristics, as well as comorbidities, were considered potential confounding
      variables in a multivariable logistic regression analysis. A sensitivity analysis
      was performed using propensity-matched analysis. RESULTS: Among the 183,833
      children included in the 2012, 2013, and 2014 ACS NSQIP database, 74,508 had a
      preoperative HCT recorded (41%). After exclusion of all children <1 year of age
      (n = 12,063), those with congenital heart disease (n = 8943), and those who
      received a preoperative red blood cell (RBC) transfusion (n = 1880), 12,551 (24%)
      children were anemic, and 39,071 (76%) were nonanemic. The median preoperative
      HCT was 33% (interquartile range, 31-35) in anemic children, and 39%
      (interquartile range, 37-42) in nonanemic children (P < .001). Using
      multivariable logistic regression analysis, and after adjustment for RBC
      transfusion (OR, 2.13; 95% CI, 1.39-3.26; P < .001), we observed that
      preoperative anemia was associated with higher odds for in-hospital mortality
      (OR, 2.17; 95% CI, 1.48-3.19; P < .001). After propensity matching, the presence
      of anemia was also associated with higher odds of in-hospital mortality (OR,
      1.75; 95% CI, 1.15-2.65; P = .004). CONCLUSIONS: Our study demonstrates that
      children with preoperative anemia are at increased risk for in-hospital
      mortality. Further studies are needed to assess whether the correction of
      preoperative HCT, through the development of a patient blood management program,
      improves patient outcomes or simply reduces the need for transfusions.

PMID- 27870742
TI  - Thoracic Paravertebral Nerve Blocks in Pediatric Patients: Safety and Clinical
      Experience.
AB  - Thoracic paravertebral nerve blocks (PVNBs) provide excellent analgesia for many
      surgeries. The primary aim was to estimate the complication rate, and secondary
      aims were to provide information on the potential clinical application of PVNBs.
      Data on 2390 PVNBs were collected. A total of 625 catheters were performed on 468
      patients, and 1765 single-injection PVNBs were performed on 403 patients. There
      was 1 case of local anesthetic systemic toxicity for a major complication rate of
      1 per 2390 PVNBs. The minor complication rate was 13.2%. We demonstrate a low
      risk of complications in pediatric patients receiving PVNBs for various
      surgeries.

PMID- 27870744
TI  - Proactive Use of Plasma and Platelets in Massive Transfusion in Trauma: The Long
      Road to Acceptance and a Lesson in Evidence-Based Medicine.

PMID- 27870743
TI  - Epidural Local Anesthetics Versus Opioid-Based Analgesic Regimens for
      Postoperative Gastrointestinal Paralysis, Vomiting, and Pain After Abdominal
      Surgery: A Cochrane Review.
AB  - BACKGROUND: The aim of this review was to compare the effects of postoperative
      epidural analgesia with local anesthetics to postoperative systemic or epidural
      opioids in terms of return of gastrointestinal transit, postoperative pain
      control, postoperative vomiting, incidence of gastrointestinal anastomotic leak,
      hospital length of stay, and cost after abdominal surgery. METHODS: Trials were
      identified by computerized searches of the Cochrane Central Register of
      Controlled Trials (CENTRAL) (2014, Issue 12), Medical Literature Analysis and
      Retrieval System Online (MEDLINE) (from 1950 to December, 2014) and Excerpta
      Medica dataBASE (EMBASE) (from 1974 to December 2014) and by checking the
      reference lists of trials retained. We included parallel randomized controlled
      trials comparing the effects of postoperative epidural local anesthetic with
      regimens based on systemic or epidural opioids. The quality of the studies was
      rated according to the Cochrane tool. Two authors independently extracted data.
      We judged the quality of evidence according to the Grading of Recommendations,
      Assessment, Development and Evaluations (GRADE) working group scale. RESULTS:
      Based on 22 trials including 1138 participants, an epidural containing a local
      anesthetic will decrease the time required for return of gastrointestinal transit
      as measured by time required to observe the first flatus after an abdominal
      surgery standardized mean difference (SMD) -1.28 (95% confidence interval [CI], 
      1.71 to -0.86; high quality of evidence; equivalent to 17.5 hours). The effect is
      proportional to the concentration of local anesthetic used. Based on 28 trials
      including 1559 participants, we also found a decrease in time to first feces
      (stool): SMD -0.67 (95% CI, -0.86 to -0.47; low quality of evidence; equivalent
      to 22 hours). Based on 35 trials including 2731 participants, pain on movement at
      24 hours after surgery is also reduced: SMD -0.89 (95% CI, -1.08 to -0.70;
      moderate quality of evidence; equivalent to 2.5 on a scale from 0 to 10). Based
      on 22 trials including 1154 participants, we did not find a difference in the
      incidence of vomiting within 24 hours: risk ratio 0.84 (95% CI, 0.57-1.23); low
      quality of evidence. Based on 17 trials including 848 participants we did not
      find a difference in the incidence of gastrointestinal anastomotic leak: risk
      ratio 0.74 (95% CI, 0.41-1.32; low quality of evidence). Based on 30 trials
      including 2598 participants, epidural analgesia reduces length of hospital stay
      for an open surgery: SMD -0.20 (95% CI, -0.35 to -0.04; very low quality of
      evidence; equivalent to 1 day). Data on cost were very limited. CONCLUSIONS: An
      epidural containing a local anesthetic, with or without the addition of an
      opioid, accelerates the return of the gastrointestinal transit (high quality of
      evidence). An epidural containing a local anesthetic with an opioid decreases
      pain after an abdominal surgery (moderate quality of evidence). An epidural
      containing a local anesthetic does not affect the incidence of vomiting or
      anastomotic leak (low quality of evidence). For an open surgery, an epidural
      containing a local anesthetic would reduce the length of hospital stay (very low
      quality of evidence).

PMID- 27870745
TI  - Does Only Size Matter or Is There Still a Place for Single-Center Studies in the
      Era of Big Data?

PMID- 27870746
TI  - Foreword.

PMID- 27870747
TI  - A Community-Based Participatory Research Intervention to Promote Physical
      Activity Among Rural Children: Theory and Design.
AB  - The overall objective of Project SHAPE (Shaping Health using Activity Photovoice
      and E-Video) was to improve physical activity levels of rural, medically
      underserved children by designing and implementing a culturally relevant physical
      activity intervention. This objective was met by using a community-based
      participatory research approach to design and implement an intervention that
      would positively affect the psychosocial constructs related to increasing
      physical activity, which, in turn, would lead to increases in the time spent in
      daily physical activity. This article describes the unique design of the
      intervention including its theoretical framework, its interrelated components,
      and the logistics involved.

PMID- 27870748
TI  - The Determinants of Physical Activity in Rural Women, Aged 20 to 44 Years, in
      Georgia.
AB  - Physical activity rates in rural women are very low. The purpose of this study
      was to explore the determinants of physical activity in rural women aged 20 to 44
      years. A survey was used to collect data on a cluster sample of 184 participants.
      This study was guided by Self-Determination Theory. Survey data suggest that the
      highest type of motivation was identified regulation, and husband's support had
      the strongest effect on physical activity. Findings suggest that a history of
      sports participation can lead to the formation of intrinsic motivation. The
      results will assist in developing effective physical activity interventions.

PMID- 27870749
TI  - Using a Community Health Development Framework to Increase Community Capacity: A
      Multiple Case Study.
AB  - The Physical Activity and Community Engagement Project utilized a comparative
      case study to understand how a theoretical framework called community health
      development (CHD) influences community capacity. Three rural communities (cases)
      developed interventions using a CHD framework. Researchers collected qualitative
      evidence measuring capacity and the CHD process for more than 3 years. Patterns
      identified seven capacity constructs relevant to CHD, including community
      history, civic participation, leadership, skills, resources, social and
      interorganizational networks, and critical reflection. Community health
      development focuses on population health improvement and strengthening community
      capacity. As such, it helps communities address local priorities and equips them
      to address future issues.

PMID- 27870750
TI  - Mapping Coaches' Views of Participation in CrossFit to the Integrated Theory of
      Health Behavior Change and Sense of Community.
AB  - Group-based training through CrossFit has recently exploded in popularity.
      Anecdotally, participants often make lifestyle changes and experience improved
      fitness. Participation factors were mapped to the Integrated Theory of Health
      Behavior Change and "sense of community" constructs. Key informant interviews
      were conducted with 6 CrossFit gym owners/coaches. Data were thematically coded
      with NVivo 10. Results revealed key factors that both facilitated and restricted
      participation in CrossFit. Findings provide implications for future theory
      application and highlight how to improve initiation and adherence by capitalizing
      on community building and taking steps to reduce intimidation and cost,
      facilitate realistic goals, and ensure social support.

PMID- 27870751
TI  - Breast-feeding Coparenting Framework: A New Framework to Improve Breast-feeding
      Duration and Exclusivity.
AB  - Targeting mothers and fathers in breast-feeding promotion programs is recommended
      as research has found that father's support positively impacts breast-feeding
      duration and exclusivity. Breast-feeding coparenting refers to the manner in
      which parents work together to achieve their breast-feeding goals. The Breast
      feeding Coparenting Framework was developed on the basis of diverse coparenting
      models and research related to father's involvement with breast-feeding. This
      framework consists of 5 components: joint breast-feeding goal setting, shared
      breast-feeding responsibility, proactive breast-feeding support,
      father's/partner's parental-child interactions, and productive communication and
      problem solving. This framework may be of value to policy makers and program
      providers working to improve breast-feeding outcomes.

PMID- 27870752
TI  - Using the Integrative Behavioral Model to Predict Monitoring of Fruit and
      Vegetable Consumption Among Hispanic Mothers.
AB  - The purpose of this study was to operationalize the Integrative Behavioral Model
      (IBM) to identify significant theory-based determinants of maternal monitoring of
      fruit and vegetables consumption among low-income, Hispanic mothers of 2- to 5
      year-old children (N = 238). Mothers completed a survey evaluating each construct
      of the IBM. Path analysis showed that intentions significantly predicted maternal
      monitoring of fruit and vegetables consumption (5.3% of the variance explained)
      and autonomy significantly predicted intentions (33.1% of the variance
      explained). Results from this study help create foundational work to establish
      targets for future public health interventions for Hispanic mothers of
      preschoolers.

PMID- 27870753
TI  - Utilizing a Social Determinant of Health Framework as Determinants of Perceived
      Behavioral Control.
AB  - Health disparities reflect inequalities in health outcomes among different
      populations. As a planning tool for researchers and practitioners to address
      health disparities, multiple frameworks utilizing social determinants of health
      have been proposed. Perceived behavioral control, a construct within the
      Integrative Behavioral Model, reflects how much control one feels over a health
      behavior and how easy or difficult the behavior is to enact under internal and
      external barriers. The purpose of this commentary is to suggest how a unified
      social determinant of health framework can be utilized as a predictor and
      determinant of the construct perceived behavioral control.

PMID- 27870754
TI  - Framed, Interactive Theory-Driven Texting: Effects of Message Framing on Health
      Behavior Change for Weight Loss.
AB  - More approaches to support weight control are needed, especially among racial
      minorities who shoulder a disproportionate obesity burden. Using an approach
      influenced by regulatory fit theory, we conducted a 28-day, 4-arm experimental
      trial with 89 obese adults recruited from urban, predominantly African American
      churches to ascertain the efficacy of framed text messages to motivate behaviors
      conducive to weight loss. Participants were assigned to receive message framing
      that was matched versus mismatched to their motivational orientation. Results
      were mixed overall; however, matched texts elicited greater motivation to change
      eating and exercise behavior, suggesting promise in using motivational approaches
      to tailor messages.

PMID- 27870755
TI  - Applying a New Theory to Alter Binge Drinking Behavior in College Students.
AB  - Binge drinking is a serious public health problem in the United States, where it
      is estimated that 17.6% adults binge drink. Binge drinking is highest among
      college students. There is need for effective binge drinking interventions.
      Recently a new health behavior theory has been proposed called the multitheory
      model of health behavior change. The purpose of this article is to describe the
      application of the multitheory model for changing binge drinking behavior to a
      behavior of responsible drinking or abstaining from alcohol. A framework for an
      intervention and its testing is presented.

PMID- 27870756
TI  - Using Multitheory Model of Health Behavior Change to Predict Adequate Sleep
      Behavior.
AB  - The purpose of this article was to use the multitheory model of health behavior
      change in predicting adequate sleep behavior in college students. A valid and
      reliable survey was administered in a cross-sectional design (n = 151). For
      initiation of adequate sleep behavior, the construct of behavioral confidence (P
      < .001) was found to be significant and accounted for 24.4% of the variance. For
      sustenance of adequate sleep behavior, changes in social environment (P < .02),
      emotional transformation (P < .001), and practice for change (P < .001) were
      significant and accounted for 34.2% of the variance.

PMID- 27870757
TI  - Examining a Partial Biopsychosocial Model for Monthly Alcohol, Tobacco, and
      Marijuana Use Among Adolescents.
AB  - Alcohol, tobacco, and marijuana are commonly used substances among adolescents.
      In the context of the Biopsychosocial Model (BPSM), this study investigated the
      relationships between psychological and normative factors associated with
      adolescent alcohol, tobacco, and marijuana use. Data were analyzed from 1053
      middle and high school students. Structural equation modeling was used to examine
      the relationships between BPSM constructs. Results indicate that latent
      constructs of the BPSM are significant antecedent factors to alcohol, tobacco,
      and marijuana use; however, the relationships between study constructs were
      inconsistent with those theorized by BPSM. Findings support the importance of
      theory testing for complex models applied to new topics and new populations.

PMID- 27870758
TI  - The Relationship Between Advertising-Induced Anger and Self-efficacy on
      Persuasive Outcomes: A Test of the Anger Activism Model Using the Truth Campaign.
AB  - Turner's Anger Activism Model (AAM) contends anger and efficacy interact in a
      unique way to determine message responses to campaign materials. This study
      tested the AAM using responses to 2 truth antismoking advertisements collected in
      August-October 2014 via an online, cross-sectional survey of 15- to 21-year-olds.
      Those aware of each of the truth advertisements (n = 319 for each) were organized
      into 4 anger/efficacy groups. Analysis of variance and regressions were conducted
      to understand group differences in message-related cognitions (persuasiveness,
      receptivity, conversation). Message cognitions were highest among the high
      anger/high efficacy group and lowest among the low anger/low efficacy group.

PMID- 27870759
TI  - "Please Don't Just Hang a Feather on a Program or Put a Medicine Wheel on Your
      Logo and Think 'Oh Well, This Will Work'": Theoretical Perspectives of American
      Indian and Alaska Native Substance Abuse Prevention Programs.
AB  - Many current theories guiding substance abuse prevention (SAP) programs stem from
      Western ideologies, leading to a scarcity of research on theories from, and a
      disconnect with, Indigenous perspectives. This qualitative research study
      explored perceptions of theory by SAP researchers (N = 22) working with American
      Indian and Alaska Native communities. In-depth interviews identified components
      of Indigenous theoretical perspectives, including cultural elements such as
      balance, social cohesion, and belonging as being particularly significant and
      currently absent from many SAP programs. Recommendations for conducting
      metatheory studies and operationalization of Indigenous perspectives into guiding
      theoretical underpinnings for future SAP programming are provided.

PMID- 27870760
TI  - Systematic Braiding of 2 Evidence-Based Parent Training Programs: Qualitative
      Results From the Pilot Phase.
AB  - An effective approach in early intervention for children and families, including
      child maltreatment prevention, is home-based services. Although several evidence
      based programs exist, they are often grouped or delivered together, despite
      having different foci and approaches. This article describes the development and
      pilot phases of a trial evaluating the systematic braiding of 2 evidence-based
      home-based models, SafeCare and Parents as Teachers. We describe the methodology
      for braiding model implementation and curriculum, specifically focusing on how
      structured qualitative feedback from pilot families and providers was used to
      create the braided curriculum and implementation. Systematic braiding of 2 models
      at the implementation and curriculum levels is a mechanism that has the potential
      to meet the more comprehensive needs of families at risk for maltreatment.

PMID- 27870761
TI  - Disease Activity Score on 28 Joints and Polypharmacy Are Independent Predictors
      for Health-Related Quality of Life Evaluated by INCAVISA in Patients With
      Rheumatoid Arthritis.
AB  - OBJECTIVE: The aim of this study was to investigate the main factors associated
      to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA
      (Health-Related Quality of Life Inventory for Latin American Patients) in
      patients with rheumatoid arthritis (RA). METHODS: Female, 18 years or older, RA
      (American College of Rheumatology 1987 criteria and American College of
      Rheumatology/European League against Rheumatism 2010 criteria) patients who
      attended the outpatient rheumatology department of the Hospital Civil "Dr. Juan
      I. Menchaca," Guadalajara, Mexico, matched with healthy controls were included.
      Patients with any known comorbidities or treatment with antidepressive drugs were
      excluded. Trained physicians performed the RA clinical evaluation and INCAVISA.
      All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05
      was considered statistically significant. RESULTS: Patients with polypharmacy
      (>=3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total
      comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively
      correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy
      were independent predictors for a negative perception of HRQoL evaluated by
      INCAVISA in RA patients. CONCLUSIONS: Disease activity and disability secondary
      to RA have a negative impact in the HRQoL. Other factors such as the number of
      drugs prescribed to these patients have been shown to be important for the
      negative perception of their HRQoL evaluated by INCAVISA.

PMID- 27870762
TI  - Review of Current Workforce for Rheumatology in the Countries of the Americas
      2012-2015.
AB  - BACKGROUND: With the increases in and aging of the populations of the Americas,
      monitoring the number of rheumatologists is critical to address and focus on
      areas of greatest need. OBJECTIVES: The aim of this study was to gather data on
      the rheumatology workforce from 21 national societies in the Pan American League
      of Associations for Rheumatology (PANLAR). METHODS: In September and October 2012
      and again in October and November 2015, the heads of the 21 rheumatology national
      societies were contacted in the 2012 survey; all national societies responded
      except Cuba. In the 2015 survey, all responded except Nicaragua, for which
      information was provided by national society presidents in adjacent countries.
      RESULTS: The data from 21 societies contained in PANLAR consist of 10,166 adult
      and 678 pediatric rheumatologists serving 961 million people. The number of
      rheumatologists per 100,000 population varies greatly from 3.9 per 100,000 people
      (Uruguay) to 0.11 per 100,000 people (Nicaragua). The number of training programs
      also varies widely, with some countries having no indigenous programs. The
      distribution of rheumatologists is mainly in the large cities, particularly in
      the smaller countries. Pediatric rheumatologists have dramatically increased in
      number in 2012, but 96% reside in 6 countries. This remains an underserved area
      in most countries. CONCLUSIONS: The rheumatology workforce in the Americas has
      improved between 2012 and 2015, especially in the number of pediatric
      rheumatologists. However, numerically and in the perception of the 21 member
      societies of PANLAR, the number is still inadequate to meet the increasing
      demands for rheumatologic care, especially in the care of children with rheumatic
      disease and in rural areas.

PMID- 27870763
TI  - The Effect of Psychosocial and Neuropsychiatric Factors on Medication Adherence
      in a Cohort of Women With Systemic Lupus Erythematosus.
AB  - BACKGROUND: Medication adherence in systemic lupus erythematosus (SLE) reduces
      disease activity and the risk of flares. OBJECTIVES: We evaluated adherence in
      women with SLE who exhibit high morbidity and mortality. We evaluated demographic
      data and 2 conventional adherence predictors: self-efficacy and health literacy,
      along with 2 potential neuropsychiatric SLE complications: cognitive dysfunction
      and depression. METHODS: One hundred six women randomly selected from the
      Barbados National Lupus Registry completed the Self-efficacy for Appropriate
      Medication Use Scale, Rapid Estimate of Adult Literacy in Medicine-Short Form,
      Cognitive Symptom Inventory, Beck Depression Inventory II, and Morisky's
      Medication Adherence Questionnaire (MAQ). This study explored the effects of
      psychosocial and neuropsychiatric functioning on adherence using ordinal logistic
      regression. RESULTS: Sixty percent reported high MAQ scores. The probability of
      high MAQ scores was lower among younger patients (P = 0.001) and those with
      shorter disease duration (P = 0.05). The probability of high MAQ scores fell with
      lower perceived self-efficacy (odds ratio [OR], 0.80; 95% confidence interval
      [CI], 0.73-0.89; P < 0.001), worsening cognitive function (OR, 0.90; 95% CI, 0.84
      0.97; P = 0.004), and increasing depression (OR, 0.93; 95% CI, 0.88-0.97; P =
      0.002). There was no strong relationship between MAQ score and health literacy
      (OR, 0.37; 95% CI, 0.13-1.03; P = 0.06). CONCLUSION: Women with SLE who are
      younger and those with shorter disease duration should be assessed for medication
      adherence. Screening at diagnosis followed by routine assessment of cognitive
      dysfunction and depression along with perceived self-efficacy may further
      identify the most vulnerable subgroup who should be targeted with personalized
      intervention strategies.

PMID- 27870764
TI  - Anti-Ro and Concomitant Anti-La Autoantibodies Strongly Associated With Anti
      oxLDL or Anti-Phospholipid Antibody in Systemic Lupus Erythematosus.
AB  - BACKGROUND: Premature atherosclerosis is observed in systemic lupus erythematosus
      (SLE). Oxidative modification of LDL is associated with atherosclerotic plaque
      formation. OBJECTIVES: We hypothesized that anti-oxidized LDL (oxLDL) and anti
      phospholipid (APL) in SLE sera would segregate with specific antibody subsets,
      and that anti-oxLDL antibodies will linger in circulation over an extended
      period. PATIENTS AND METHODS: Sixty-seven SLE and control subjects and two SLE
      subjects with sera collected longitudinally for 13 years were tested for anti
      oxLDL and IgG/IgM/IgA APL antibodies. RESULTS: Anti-oxLDL ELISA values above
      57.48 Activity Units (AcU) (means of normals + 3 standard deviations) and anti
      IgG/IgM/IgA APL above 10 phospholipid units (PU) were considered positive.
      Average anti-oxLDL was 67.7 +/- 50.5 AcU in SLE compared to 23.9 +/- 11.19 AcU in
      normals (P = 0.018). Ten out of ten subjects with anti-Ro60/anti-La/anti-Ro52
      antibodies had highly significant (P < 0.0001) anti-oxLDL (127.29 +/- 45.67 AcU)
      and IgG APL (18.66 +/- 7.4 PU) (P < 0.02). Subjects with anti-RNP were positive
      for anti-oxLDL (P < 0.002), but subjects with anti-Ro60/anti-Ro52 and subjects
      negative for extractable nuclear antigen (ENA) antibody were not positive for
      anti-oxLDL. Anti-oxLDL/anti-IgG APL remained significantly elevated in two
      patients studied longitudinally. Interestingly, one developed anti-oxLDL/anti-APL
      antibodies several years before anti-Ro60 development. CONCLUSIONS: Presence of
      antibodies against Ro RNP and La, and RNP is highly associated with developing
      anti-oxLDL and APL antibodies in SLE. It will be clinically important to see if
      cardiovascular events occur in these SLE subsets having elevated anti-oxLDL and
      APL antibodies. Emergence of anti-oxLDL/IgG APL before anti-Ro60 over time in a
      patient indicates that these antibodies could not be cross-reactive in nature, at
      least in this particular patient.

PMID- 27870765
TI  - Accelerated Age-Related Arterial Stiffness in Systemic Lupus Erythematosus
      Patients.
AB  - BACKGROUND: An increased prevalence of arterial stiffness in systemic lupus
      erythematosus (SLE) patients has been established, but the mechanisms of
      progression of arterial stiffness with increasing age have not been fully
      explored. OBJECTIVES: To investigate age-related progression of arterial
      stiffness among SLE patients relative to healthy controls. METHODS: A total of
      161 female SLE patients who were enrolled in the Chinese SLE Treatment and
      Research group (CSTAR) registry and 135 age-matched healthy control subjects
      participated in this cross-sectional investigation. Traditional cardiovascular
      risk factors and SLE-related parameters were assessed on the day that brachial
      ankle pulse wave velocity (baPWV) was examined. SAS 9.3 was used to perform all
      statistical analyses in this study. Linear regression and curvilinear regression
      models were utilized to analyze the association between age and arterial
      stiffness. RESULTS: Arterial stiffness based on baPWV significantly differed
      between the SLE patients and controls in the different age groups, and within the
      SLE group. The baPWV increments for each age group (<25, 25-34, 35-45, and >45)
      were 30 cm/s, 52 cm/s, and 121 cm/s for the controls and 61 cm/s, 132 cm/s, and
      155 cm/s for the SLE patients, respectively. Curvilinear regression and linear
      regression revealed various trends of increased arterial stiffness among the SLE
      patients compared with the healthy controls. The correlation coefficients between
      age and arterial stiffness significantly differed among the SLE patients relative
      to the healthy controls (correlation coefficients of 0.46478 and 0.52612,
      respectively; t = 2.05; P = 0.0409). Multivariate analysis revealed that age,
      mean blood pressure (BP) (P < 0.0001), erythrocyte sedimentation rate (ESR) (P =
      0.0073), prednisone course (P = 0.0144), and SLE disease activity (P = 0.0405)
      were associated with arterial stiffness among the SLE patients. Further, these
      patients exhibited earlier exposure to and higher frequencies of several risk
      factors compared with the controls in each age group (<25 years: OR = 6.3253; 25
      34 years: OR = 3.1043; 35-45 years: OR = 3.1316; >45 years: OR = 3.6020).
      CONCLUSIONS: The mechanisms of the age-related progression of arterial stiffness
      differed among the SLE patients relative to the healthy controls. Furthermore,
      accelerated arterial stiffness was observed among the SLE patients relative to
      the healthy controls with advancing age.

PMID- 27870766
TI  - The Expanding Mosaic of Autoinflammatory Disease.

PMID- 27870767
TI  - Flagellate Erythema in a Case of Paraneoplastic Dermatomyositis.

PMID- 27870768
TI  - Proton Pump Inhibitor-Associated Subacute Cutaneous Lupus Erythematosus in a
      Patient With Granulomatosis With Polyangiitis.

PMID- 27870769
TI  - Brown Tumors in Secondary Hyperparathyroidism in a Patient With Lupus Nephritis.

PMID- 27870770
TI  - Alternate Definitions.

PMID- 27870771
TI  - Multiorgan Failure From Cryoglobulinemic Vasculitis Following Intravenous
      Immunoglobulin Replacement Therapy.

PMID- 27870772
TI  - Strawberry Gingivitis: First Manifestation of a Vasculitic Disorder in a Young
      Child.

PMID- 27870773
TI  - Tofacitinib Response in Juvenile Idiopathic Arthritis (JIA) and Collagenous
      Colitis.

PMID- 27870774
TI  - Absence of Association of Joint Tenderness and High-Resolution Ultrasound
      Findings in Established Rheumatoid Arthritis.

PMID- 27870777
TI  - Minocycline-Induced Scleral and Dermal Hyperpigmentation.
AB  - PURPOSE: To present a case of minocycline-induced blue scleral pigmentation and
      discuss the pathophysiology and differential diagnoses. The uses, mechanisms, and
      other adverse effects of minocycline will also be highlighted. CASE REPORT: An
      elderly Caucasian male patient presented for routine ocular examination
      complaining of blue discoloration to the whites of his eyes. He was found to have
      bilateral blue scleral pigmentation and blue discoloration to various other
      dermal areas of his body. The blue pigmentation was also visible in the posterior
      segment within a scleral crescent around his right optic nerve. This pigmentation
      was determined to be caused by long-term use of oral minocycline. CONCLUSIONS:
      Long-term minocycline use may induce scleral, dermal, and organ
      hyperpigmentation, typically blue or black in coloration. The pigmentation may
      reverse with discontinuation of the medication, but can also be permanent. The
      exact mechanism of pigment deposition remains uncertain, but several theories
      have been proposed. While the cosmetic appearance may be dramatic, this side
      effect is not known to cause any systemic or ocular morbidity.

PMID- 27870778
TI  - Inter-visit Test-Retest Variability of OCT in Glaucoma.
AB  - PURPOSE: To determine the inter-visit test-retest variability (TRV) of a spectral
      domain optical coherence tomograph, the Topcon 3D OCT-2000, in the measurement of
      optic nerve head topography, peripapillary retinal nerve fiber layer (pRNFL), and
      macular ganglion cell complex (GCC) parameters in glaucoma patients. We also
      examine whether TRV with this instrument varies with the extent of glaucomatous
      damage. METHODS: Twenty-four subjects with varying degrees of glaucoma severity
      provided 41 eyes with usable results for the study. 3D Disc Retinal Nerve Fiber
      Layer Analysis and Macula V (GCC) scans were repeated 1 week apart, at the same
      time of day, to determine the inter-visit TRV. TRV was determined using Bland
      Altman limits of agreement (LoA) and the resulting coefficients of repeatability
      (CR). RESULTS: The overall horizontal and vertical cup/disc ratio CRs were 0.05
      and 0.07, respectively. The GCC CR was 2.9 MUm. In contrast, average pRNFL TRV
      expanded with increasing damage, with the LoA being well fitted by +/-(34.67 -
      0.294(d)), where d is the pRNFL thickness. A more complex model, with constant
      LoA of +/-5.61 MUm at d >82 MUm, and linearly expanding TRV below that, achieved
      marginal significance (P < .06). CONCLUSIONS: The repeatability of GCC
      measurements with this instrument was excellent. The determination of
      statistically significant change in average pRNFL should take into account
      average pRNFL thickness.

PMID- 27870779
TI  - Painless Acanthamoeba Keratitis with Normal Vision.
AB  - PURPOSE: To report an atypical case of contact lens-related Acanthamoeba
      keratitis. CASE REPORT: A 15-year-old secondary school female student with a
      history of soft contact lens wear was referred to our hospital by a private
      general practitioner for management of right eye redness and discomfort for 2
      weeks. Upon examination, the best-corrected visual acuity was 20/20 and 20/16 for
      her right and left eyes, respectively. There was diffuse radial keratoneuritis
      noted in the cornea of her right eye without any associated epithelial defect.
      Corneal scraping was performed to induce epithelial defect over the
      keratoneuritis area, and it was positive for Acanthamoeba trophozoites. She was
      treated with amoebicidal therapy consisting of propamidine isethionate 0.1% and
      polyhexamethylene biguanide 0.02%, for 6 months. The patient did not complain of
      any ocular pain in the entire course of her disease. She attained a final visual
      acuity of 20/13 in the affected eye with residual peripheral radial perineuritic
      scar. CONCLUSIONS: Atypical presentation of Acanthamoeba infection is uncommon.
      This case should arouse the awareness of an indolent presentation of this
      potentially sight-threatening disease. Clinicians should have a high level of
      suspicion in contact lens users who present with corneal abnormalities despite an
      absence of pain. Microbiological work-up and prompt treatment led to a complete
      resolution of Acanthamoeba infection in our patient.

PMID- 27870780
TI  - The activation of metabotropic glutamate 5 receptors in the rat ventral tegmental
      area increases dopamine extracellular levels.
AB  - The mesocorticolimbic circuit projects to the prefrontal cortex, hippocampus,
      amygdala, and nucleus accumbens, among others, and it originates in the
      dopaminergic neurons of the ventral tegmental area (VTA). The VTA receives
      glutamatergic inputs from the prefrontal cortex and several subcortical regions.
      The glutamate released activates dopaminergic neurons and its action depends on
      the activation of ionotropic and metabotropic glutamate receptors. VTA
      dopaminergic neurons release dopamine (DA) from axon terminals in the innervated
      regions and somatodendritically in the VTA itself. DA release in the VTA is
      directly correlated with the activity of dopaminergic neurons. We hypothesized
      that metabotropic glutamate 5 receptors (mGlu5) directly regulate the activity of
      VTA dopaminergic neurons. To test this hypothesis, the extracellular levels of
      VTA DA and glutamate were studied by in-vivo microdialysis after an intra-VTA
      perfusion of (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG), selective mGlu5
      agonist. We observed that CHPG induced a significant increase in VTA DA and
      glutamate extracellular levels. To determine whether the effect of CHPG on DA
      levels is because of the increase in glutamate release, we perfused kynurenic
      acid, an ionotropic glutamate receptor antagonist, through the probe. Our results
      showed that kynurenic acid did not block the ability of CHPG to cause DA release.
      Thus, our results suggest that CHPG acts directly on mGlu5 in dopaminergic
      neurons to induce the release of DA.

PMID- 27870781
TI  - Neuroanatomical assessment of the impact of negative emotion on explicit memory
      in patients with obsessive-compulsive disorder.
AB  - The aim of this study was to identify the brain activation patterns associated
      with emotionally neutral or unpleasant words during explicit memory tasks in
      patients with obsessive-compulsive disorder (OCD) using a functional MRI. Sixteen
      patients with OCD (mean age=31.4+/-10.1 years) and 16 healthy controls (mean
      age=32.6+/-5.8 years) who had no history of neurological or psychiatric illness
      underwent functional MRI examinations on a 3-T Siemens MR Scanner. The
      stimulation paradigm consisted of five times rest-condition, two times encoding
      of two-syllable words, and two times explicit retrieval of the previously learned
      words. Six different words were presented for 3 s each in the encoding and
      retrieval tasks. In the retrieval task, the same words as those used at the
      encoding task were presented randomly. Brain activation maps were quantified and
      analyzed using SPM8 and MRIcron software. During the explicit retrieval tasks
      with emotionally neutral words, the predominant activation areas observed in
      patients with OCD included the angular gyrus and the supramarginal gyrus, whereas
      healthy controls showed significantly higher activity in the postcentral gyrus
      (P<0.005). During the explicit retrieval tasks with unpleasant words, patients
      with OCD showed significantly higher activity, compared with healthy controls, in
      the cerebellum, posterior cingulate gyrus, middle occipital gyrus, middle
      temporal gyrus, and inferior frontal gyrus (P<0.005); however, no predominant
      activation areas in healthy controls over patients with OCD were observed. This
      study showed differential brain activation patterns in response to emotionally
      neutral and unpleasant words in patients with OCD. This finding will be useful in
      assessing the neural mechanisms associated with emotional effect on the
      impairment of memory retrieval in OCD.

PMID- 27870782
TI  - Safety of Laparoscopic Colorectal Resection in Patients With Severe
      Comorbidities.
AB  - We aimed to assess the safety of laparoscopic colorectal resection in patients
      with severe comorbidities. High operative risk was defined as an American Society
      of Anesthesiologists (ASA) class 3 score. Outcomes in 34 patients with an ASA
      score of 3 undergoing laparoscopic surgery (LAP3) were compared with 172
      laparoscopic surgery patients with an ASA score <=2 (LAP2) and 32 laparotomy
      patients with an ASA score of 3 (OP3). The postoperative complication rate in
      LAP3 was similar to that seen in LAP2 and significantly lower than that seen in
      OP3 (LAP2, 4.0%; LAP3, 5.9%; OP3, 31.2%). The incidence of postoperative
      hemorrhage, infection, ileus, and anastomotic leakage was similar between LAP3
      and LAP2 and between LAP3 and OP3. However, the systemic complication rate in
      LAP3 was similar to that seen in LAP2 and significantly lower than that seen in
      OP3. Laparoscopic colorectal resection can be performed safely in patients with
      severe comorbidities.

PMID- 27870783
TI  - Preperitoneal Suction Technique to Secure the Proper Mesh Position During
      Laparoscopic Herniorrhaphy.
AB  - PURPOSE: Dislocation of the mesh is 1 cause of recurrence after laparoscopic
      inguinal hernia repair (LIHR). Here, we propose a new procedure, the
      "preperitoneal cavity suction technique," to confirm mesh position during LIHR
      under a transabdominal preperitoneal approach (TAPP). PATIENTS AND METHODS: We
      developed the "preperitoneal cavity suction technique" during LIHR by TAPP,
      visualizing the mesh through the closed peritoneum by vacuuming up the carbon
      dioxide and effusion at the preperitoneal cavity using a suction tube inserted
      through the tunnel from a laterally placed trocar into the preperitoneal space.
      We applied this technique in adults with inguinal hernias who were scheduled to
      undergo elective surgery in our hospital between April 2013 and March 2015.
      RESULTS: In total, 84 lesions were treated in 74 consecutive LIHRs by TAPP. The
      "preperitoneal cavity suction technique" was applied to 83 lesions. We confirmed
      appropriate positioning of the mesh for 82 of the 83 lesions (98.8%), with
      dislocation of the mesh detected in 1 case. In that case, we reopened the
      peritoneal flap and repositioned the mesh correctly during the operation. No
      patients complained of pain or a sense of discomfort, and no hematoma was
      identified around the dissected area or anterior superior iliac spine on the
      affected side. Mean duration of hospitalization was 2.5 days. No cases of hernia
      recurrence were observed during follow-up (range, 7 to 31 mo; median, 15 mo).
      CONCLUSIONS: The "preperitoneal suction technique" seems useful to detect mesh
      dislocation and has potential to reduce TAPP-related complications.

PMID- 27870784
TI  - Intussusception With Cecal Cyst as Lead Point in a Child.
AB  - Intussusception is a pediatric abdominal emergency in early childhood involving
      telescoping of 1 part of the bowel into another part. In most children, the
      condition is idiopathic with no identifiable lead point. Meckel diverticulum is
      the most common lead point, followed by polyps and duplication cysts. We describe
      a case of a boy with intussusception caused by a duplication cyst that was drawn
      retrograde through the ileocecal valve. The patient presented after a 3-month
      period of symptomatology and had been considered to have constipation before
      signs of intestinal obstruction developed. Only mild bowel ischemia was seen
      during the surgical reduction and resection of the cyst which may suggest an
      ongoing partial obstruction that eventually became more significant. In children
      with recurrent abdominal pain, surgeons should consider the possibility of
      intermittent intussusceptions caused by a duplication cyst.

PMID- 27870785
TI  - Abdominal Pain Caused by a Potentially Fatal Attraction.
AB  - Abdominal pain is a challenging presentation in children. Examination findings
      and etiology vary greatly, spanning a vast spectrum from flatulence to frank
      peritonitis with septic shock. Here, we discuss a 10-year-old boy with 24 hours
      of progressively worsening lower abdominal pain, nausea, and subjective fevers.
      History and physical examination findings were consistent with appendicitis.
      However, physicians were surprised when the single-view abdominal radiograph
      showed an unanticipated, somewhat perplexing discovery.

PMID- 27870786
TI  - Editor's Introduction: The Future of Ultrasound.

PMID- 27870787
TI  - Can Nodular Hyperplasia of the Thyroid Gland be Differentiated From Follicular
      Adenoma and Follicular Carcinoma by Ultrasonography?
AB  - OBJECTIVES: The aim of this study was to evaluate the ultrasonographic features
      for differentiation of follicular thyroid lesions. METHODS: Ultrasonographic
      features of surgically confirmed 56 follicular adenoma (FA), 22 follicular
      carcinoma (FC), and 100 nodular hyperplasia (NH) were evaluated using univariable
      and multivariable multinomial logistic regression analyses, receiver operating
      characteristic analyses, and areas under the curve. RESULTS: Tumor diameter,
      margin, echotexture, cystic changes, calcification, hypoechoic rim, and
      vascularity were significant on univariable analysis. On multivariable logistic
      regression analyses, tumor diameter (FA, P = 0.002; odds ratio [OR], 0.75; FC, P
      = 0.001; OR, 2.02), absence of cystic changes (FA, P = 0.127; OR, 2.21; FC, P <=
      0.001; OR, 17.74), absence of spongiform appearance (FA, P = 0.234; OR, 0.31; FC,
      P < 0.001; OR,  1673.46), and peripheral vascularity (FA, P = 0.004; OR, 26.64;
      FC, P < 0.001; OR, 145060.38) differed significantly among the 3 follicular
      lesions, with NH as a reference. The areas under the curve for NH, FA, and FC
      were 0.844, 0.858, and 0.705, respectively, and diagnostic accuracy was 72.6%.
      CONCLUSIONS: Tumor diameter, cystic changes, spongiform appearance, and
      peripheral vascularity differed significantly among follicular lesions. The
      diagnostic capability was moderate.

PMID- 27870788
TI  - Prenatal Ultrasound Evaluation of the Position of Conus Medullaris for the
      Diagnosis of Tethered Cord Syndrome.
AB  - To determine the conus distance between the end of the conus medullaris and the
      distal end of the last vertebral body in healthy fetuses with various gestational
      ages using ultrasonography for its diagnostic value in tethered cord syndrome
      (TCS). This retrospective study included 540 healthy and 8 autopsy-confirmed TCS
      fetuses. Ultrasonographic measurement of the conus distance was performed when
      the fetus was in a prone position within the spine in the near field at 14 to 41
      weeks of gestational age. Linear correlation analysis was performed to analyze
      the relationship between the conus distance and the gestational age, biparietal
      diameter, femur length, head circumference, and abdominal circumference. The
      normal results were compared with 8 cases of postnatally confirmed TCS. In 526
      (95.9%) of 548 fetuses, the conus distance was successfully measured. The 95%
      limits of agreement in measurement of conus distance were -2.2 to 2.6 mm for the
      intraobserver variability and -3.7 to 3.1 mm for the interobserver variability.
      Significant correlations between the conus distance and the gestational age,
      biparietal diameter, femur length, head circumference, and abdominal
      circumference were observed. The most marked association was found to be between
      conus distance and femur length. The conus distance was significantly less in TCS
      fetuses than in healthy fetuses. Ultrasonographic measurement of conus distance
      is an easy and reliable method to evaluate the position of the conus medullaris
      and, therefore, can be helpful in the prenatal diagnosis of TCS.

PMID- 27870789
TI  - Breaking Borders: A Case Report of Borderline Ovarian Tumor in the Pregnant
      Patient.

PMID- 27870790
TI  - Case Report of a Uterine Angioleiomyoma.

PMID- 27870794
TI  - Comparison of Measures of Maximal and Submaximal Fitness in Response to Exercise.
AB  - INTRODUCTION: Adoption of physical activity (PA) consistent with current
      guidelines does not improve maximal cardiorespiratory fitness (mCRF; VO2peak)
      beyond the error of measurement for approximately 30% of adults. Whether PA
      improves measures of exercise tolerance at submaximal levels (submaximal
      cardiorespiratory fitness [sCRF]) independent of change in mCRF is unknown. Here
      we assessed the relationship between exercise-induced changes in mCRF and sCRF.
      METHODS: Twenty-five physically inactive men 30-60 yrs old (mean +/- SD = 44.3 +/
      9.1 yr) completed 4 wk of supervised exercise consisting of 30 min of exercise,
      five times per week at 65% mCRF. mCRF was assessed using a maximal treadmill
      test. sCRF was measured as follows: 1) exercise tolerance, the distance traveled
      during a 12-min time trial on a treadmill, and 2) change in heart rate (HR) at
      submaximal work rates during the maximal treadmill test. Daily PA was measured by
      accelerometry at baseline and 4 wk. RESULTS: mCRF (P = 0.009) and both measures
      of sCRF (P < 0.001) improved at 4 wk. No change in measures of daily PA was
      observed at 4-wk compared with baseline (P > 0.05). No association was observed
      between exercise-induced change in mCRF and change in either measure of sCRF (P >
      0.05) after exercise training. In the group of participants who did not improve
      mCRF beyond the measurement error (n = 13, or 52%), we observed a significant
      improvement in both measures of sCRF (P < 0.001). Among these 13 individuals, all
      improved in at least one measure of sCRF. CONCLUSION: Exercise-induced
      improvements in mCRF were not associated with improvements in either measure of
      sCRF. Improvements in submaximal measures of cardiorespiratory fitness are
      observed in the absence of change in mCRF. Measures of sCRF capture peripheral
      adaptations to exercise not captured by measures of mCRF alone.

PMID- 27870795
TI  - Achieving Equity in Physical Activity Participation: ACSM Experience and Next
      Steps.
AB  - There is clear and consistent evidence that regular physical activity is an
      important component of healthy lifestyles and fundamental to promoting health and
      preventing disease. Despite the known benefits of physical activity
      participation, many people in the United States remain inactive. More
      specifically, physical activity behavior is socially patterned with lower
      participation rates among women; racial/ethnic minorities; sexual minority youth;
      individuals with less education; persons with physical, mental, and cognitive
      disabilities; individuals >65 yr of age; and those living in the southeast region
      of the United States. Many health-related outcomes follow a pattern that is
      similar to physical activity participation. In response to the problem of
      inequities in physical activity and overall health in the United States, the
      American College of Sports Medicine (ACSM) has developed a national roadmap that
      supports achieving health equity through a physically active lifestyle. The
      actionable, integrated pathways that provide the foundation of ACSM's roadmap
      include the following: 1) communication-raising awareness of the issue and
      magnitude of health inequities and conveying the power of physical activity in
      promoting health equity; 2) education-developing educational resources to improve
      cultural competency for health care providers and fitness professionals as well
      as developing new community-based programs for lay health workers; 3)
      collaboration-building partnerships and programs that integrate existing
      infrastructures and leverage institutional knowledge, reach, and voices of
      public, private, and community organizations; and 4) evaluation-ensuring that
      ACSM attains measurable progress in reducing physical activity disparities to
      promote health equity. This article provides a conceptual overview of these four
      pathways of ACSM's roadmap, an understanding of the challenges and advantages of
      implementing these components, and the organizational and economic benefits of
      achieving health equity.

PMID- 27870798
TI  - RETINAL ANGIOMATOUS PROLIFERATION DIAGNOSIS: A Multiimaging Approach.
AB  - PURPOSE: To identify signs occurring more frequently in retinal angiomatous
      proliferation (RAP) lesions compared with other types of choroidal
      neovascularization (CNV) in age-related macular degeneration. METHODS: In this
      cross-sectional retrospective study, 30 patients were evaluated. These signs were
      correlated with the type of CNV: shunting of blood flow to the lesion by
      fluorescein angiography, late leakage by indocyanine green angiography,
      intraretinal cysts and retinal pigmented epithelium interruption along the
      retinal pigmented epithelium detachment with a hyperreflective oval area by
      spectral domain optical coherence tomography, and presence of reticular
      pseudodrusen by infrared light. RESULTS: Shunting of blood flow was found in 56%
      of RAP, whereas it was absent in 100% of other CNVs. Late leakage in indocyanine
      green angiography occurred in all RAP cases, while it was found in 7% of other
      CNVs. Intraretinal cysts were detected in 100% of RAP cases and in 14% of other
      CNVs. Retinal pigmented epithelium interruption along the retinal pigmented
      epithelium detachment was evident in 93% of RAP cases and in 15% of other CNVs.
      Reticular pseudodrusen were present in 87% of RAP cases and in 21% of other CNVs.
      CONCLUSION: All the signs investigated were strongly associated to RAP lesions. A
      multimodal imaging approach may help differentiating subtypes of
      neovascularization.

PMID- 27870799
TI  - CHOROIDAL THICKNESS CHANGES AFTER INTRAVITREAL DEXAMETHASONE IMPLANT INJECTION
      FOR THE TREATMENT OF MACULAR EDEMA DUE TO RETINAL VEIN OCCLUSION.
AB  - PURPOSE: To investigate changes in choroidal thickness after intravitreal
      injection of a dexamethasone implant for macular edema due to retinal vein
      occlusion. METHODS: Thirty-one eyes of 31 patients, treated with a single dose of
      a dexamethasone implant for retinal vein occlusion-associated macular edema, were
      included. Subfoveal choroidal thickness (SFCT) and central macular thickness of
      the affected eyes were compared with those of the normal contralateral eyes at
      baseline and 1, 3, and 5 months after injection. RESULTS: The mean SFCT of the
      affected eyes (296.3 MUm +/- 61.6 MUm) was significantly higher than that of the
      contralateral eyes (251.2 MUm +/- 57.7 MUm; P < 0.001) at baseline. After
      injection, the mean SFCT was decreased compared with baseline in the treated eyes
      at months 1, 3, and 5. There was a correlation between SFCT and central macular
      thickness in the affected eyes at baseline (r = 0.397, P = 0.027). The change in
      SFCT was not correlated with the change in central macular thickness after
      injection. In the contralateral eyes, the mean SFCT did not change significantly.
      CONCLUSION: Subfoveal choroidal thickness in eyes with macular edema due to
      retinal vein occlusion was higher than that of the contralateral eyes.
      Intravitreal injection of a dexamethasone implant was associated with a reduction
      in the choroidal thickness of the treated eye.

PMID- 27870800
TI  - POSTOPERATIVE INNER NUCLEAR LAYER MICROCYSTS AFFECTING LONG-TERM VISUAL OUTCOMES
      AFTER EPIRETINAL MEMBRANE SURGERY.
AB  - PURPOSE: To investigate the risk factors and long-term visual impact of
      microcysts in the inner nuclear layer developed after epiretinal membrane (ERM)
      surgery. METHODS: This study used a retrospective review of medical records,
      operative video and images of patients who had undergone idiopathic ERM surgery
      with more than 12 months of follow-up. RESULTS: This study enrolled 44 patients
      (44 eyes) with ERM and a mean follow-up period of 30.2 months. The visual acuity
      improved from a mean of 6/22.8 to 6/12 (P < 0.001). Results indicated that a
      final visual acuity greater than 0.5 was associated with younger age, better
      preoperative visual acuity, a complete postoperative inner segment and outer
      segment line, and absence of inner nuclear layer microcysts. The visual acuity
      difference between patients with and without inner nuclear layer microcysts
      emerged in the first month and continued throughout the entire study period.
      Shorter duration of visual symptoms, more severe grade of ERM with paravascular
      abnormalities, and retinal petechiae immediately after the peeling of the ERM are
      risk factors of microcysts. CONCLUSION: This study suggests that inner nuclear
      layer microcysts are induced shortly after surgery and have long-term visual
      effects. Factors associated with this side effect suggest that severity,
      acuteness, and adhesiveness of ERM may play a significant role in visual
      outcomes.

PMID- 27870801
TI  - RELATIONSHIP BETWEEN UVEITIS, DIFFERENT TYPES OF VIRAL HEPATITIS, AND LIVER
      CIRRHOSIS: A 12-Year Nationwide Population-Based Cohort Study.
AB  - PURPOSE: This study investigates whether patients with viral hepatitis and
      cirrhosis are at risk of uveitis in the years following hepatitis. METHODS: We
      used data from Taiwan National Health Insurance system. The cases were patients
      newly diagnosed with viral hepatitis from 2000 to 2011. The end point of interest
      was a diagnosis of uveitis. A chi-square test was used for the difference of
      demographic characteristics between viral hepatitis and comparison. The risk of
      uveitis in hepatitis was stratified using Cox proportional hazard regression.
      RESULTS: We selected 17,389 patients with viral hepatitis and 34,778 matched
      comparison. The risk of uveitis in hepatitis cohort was 1.30-fold (95% confidence
      interval = 1.01-1.69). Patients with hepatitis B virus and hepatitis C virus
      coinfection had the highest risk (hazard ratio = 2.88; 95% confidence interval =
      1.07-7.78), and followed by only hepatitis C virus infection (hazard ratio =
      1.75; 95% confidence interval = 1.10-2.79). Patients with cirrhosis had a higher
      risk in the multivariable model but did not attach statistic difference.
      CONCLUSION: Patients with hepatitis B virus and hepatitis C virus coinfection had
      the highest risk of uveitis. In patients with hepatitis C virus and/or hepatitis
      B virus infection, the symptoms of uveitis should be alerted. Although these
      epidemiologic studies yielded informative results, the underlying mechanisms and
      the host's genetic factors remain to be investigated.

PMID- 27870803
TI  - THREE-DIMENSIONAL CHARACTERISTICS OF FOUR MACULAR INTRARETINAL LAYER THICKNESSES
      IN SYMPTOMATIC AND ASYMPTOMATIC CARRIERS OF G11778A MUTATION WITH LEBER'S
      HEREDITARY OPTIC NEUROPATHY.
AB  - PURPOSE: To characterize by spectral domain optical coherence tomography the
      three-dimensional thicknesses of four macular intraretinal layers in symptomatic
      and asymptomatic carriers of G11778A mutation with Leber's hereditary optic
      neuropathy. METHODS: Twenty-five eyes (7 symptomatic eyes and 18 asymptomatic
      eyes) of patients with Leber's hereditary optic neuropathy from one Chinese
      family and 16 normal eyes were enrolled. Macular radial scans by spectral domain
      optical coherence tomography and custom software produced intraretinal three
      dimensional thickness maps. The macula was divided into nine regions, and each
      region included four intraretinal layers: nerve fiber layer, ganglion cell layer
      and inner plexiform layer, inner nuclear layer and outer plexiform layer, and the
      outer retinal layer. RESULTS: Nerve fiber layer in the symptomatic eyes was
      significantly thinner than in normal eyes for most of the macular regions;
      however in the asymptomatic eyes, it was increased in three regions. Ganglion
      cell layer and inner plexiform layers in all regions of symptomatic eyes were
      significant thinner than in asymptomatic eyes and controls. Inner nuclear layer
      and outer plexiform layers in six regions of symptomatic and asymptomatic eyes
      were significantly thicker than in controls. The outer retinal layer of
      asymptomatic eyes was thicker than in most control regions. CONCLUSION:
      Intraretinal thickness changes in asymptomatic patients could be prodromal events
      that indicate the imminent conversion to symptomatic patients with Leber's
      hereditary optic neuropathy.

PMID- 27870802
TI  - INTRAVITREAL INFLIXIMAB IN REFRACTORY UVEITIS IN BEHCET'S DISEASE: A Safety and
      Efficacy Clinical Study.
AB  - PURPOSE: To assess the safety and efficacy of intravitreal infliximab (1 mg/0.05
      mL) in patients with refractory posterior uveitis in Behcet's disease. METHODS:
      Twenty patients were included in this study. Best corrected visual acuity (BCVA),
      vitreous haze (graded 0-4), vasculitis, retinitis, and papillopathy (presence or
      absence) were assessed at baseline, Day 1 and Week 2, 4, 6, 8, 12, and 18.
      Optical coherence tomography (OCT) central foveal thickness, fluorescein
      angiography, and flash electroretinogram were done at baseline and 4, 12, and 18
      weeks. RESULTS: Mean baseline logMAR BCVA was 0.94 (20/160), had improved
      significantly by Week 2 to 0.6 (20/80) (P < 0.0001), and reached 0.36 (20/40) by
      Weeks 18 with three injections (P < 0.0001). Mean central foveal thickness OCT
      decreased significantly from baseline 361 MUm to 180 MUm at the end of follow-up
      (P < 0.0001). Profound decrease in mean vitreous haze gradings from two to 0.2 by
      the end follow-up (P < 0.05). There was a significant reduction in the number of
      patients with vasculitis (15 at baseline to 1 weeks at 18 weeks), retinitis (nine
      at baseline to none at 4 weeks), and papillitis (two at baseline to none at 4
      weeks) (P < 0.05). No significant electrophysiological changes or ocular adverse
      inflammatory reactions were observed during the study period. CONCLUSION:
      Intravitreal infliximab appeared to be safe and effective in treating uveitis in
      Behcet's disease and should be considered as an alternative to systemic
      therapies.

PMID- 27870805
TI  - Minimum Clinically Important Difference: Current Trends in the Spine Literature.
AB  - STUDY DESIGN: Review of the 2011 to 2015 minimum clinically important difference
      (MCID)-related publications in Spine, Spine Journal, Journal of Neurosurgery
      Spine, and European Spine Journal. OBJECTIVE: To summarize the various
      determinations of MCID and to analyze its usage in the spine literature of the
      past 5 years in order to develop a basic reference to help practitioners
      interpret or utilize MCID. SUMMARY OF BACKGROUND DATA: MCID represents the
      smallest change in a domain of interest that is considered beneficial to a
      patient or clinician. The many sources of variation in calculated MCID values and
      inconsistency in its utilization have resulted in confusion in the interpretation
      and use of MCID. METHODS: All articles from 2011 to 2015 were reviewed. Only
      clinical science articles utilizing patient reported outcome scores (PROs) were
      included in the analysis. A keyword search was then performed to identify
      articles that used MCID. MCID utilization in the selected papers was
      characterized and recorded. RESULTS: MCID was referenced in 264/1591 (16.6%)
      clinical science articles that utilized PROs: 22/264 (8.3%) independently
      calculated MCID values and 156/264 (59.1%) used previously published MCID values
      as a gauge of their own results. Despite similar calculation methods, there was a
      two- or three-fold range in the recommended MCID values for the same instrument.
      Half the studies recommended MCID values within the measurement error. Most
      studies (97.2%) using MCID to evaluate their own results relied on generic MCID.
      The few studies using specific MCID (MCID calculated for narrowly defined
      indications or treatments) did not consistently match the characteristics of
      their sample to the specificity of the MCID. About 48% of the studies compared
      group averages instead of individual scores to the MCID threshold. CONCLUSION:
      Despite a clear interest in MCID as a measure of patient improvement, its current
      developments and uses have been inconsistent. LEVEL OF EVIDENCE: N/A.

PMID- 27870804
TI  - Effects of Low-Load Motor Control Exercises and a High-Load Lifting Exercise on
      Lumbar Multifidus Thickness: A Randomized Controlled Trial.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: The aim of this study was
      to compare the effects of low-load motor control (LMC) exercises and a high-load
      lifting (HLL) exercise, on lumbar multifidus (LM) thickness on either side of the
      spine and whether the effects were affected by pain intensity or change in pain
      intensity. SUMMARY OF BACKGROUND DATA: There is evidence that patients with low
      back pain (LBP) may have a decreased size of the LM muscles with an asymmetry
      between sides in the lower back. It has also been shown that LMC training can
      affect this asymmetry. It is, however, not known whether a high-load exercise has
      the same effect. METHODS: Sixty-five participants diagnosed with nociceptive
      mechanical LBP were included and randomized into LMC exercises or a HLL exercise,
      the deadlift. The LM thickness was measured using rehabilitative ultrasound
      imaging (RUSI), at baseline and after a 2-month training period. RESULTS: There
      were no differences between interventions regarding effect on LM muscle
      thickness. However, the analysis showed a significant effect for asymmetry. The
      thickness of the LM muscle on the small side increased significantly compared
      with the large side in both intervention groups, without influence of pain at
      baseline, or change in pain intensity. CONCLUSION: At baseline, there was a
      difference in thickness of the LM muscles between sides. It seems that exercises
      focusing on spinal alignment may increase the thickness of the LM muscles on the
      small side, irrespective of exercise load. The increase in LM thickness does not
      appear to be mediated by either current pain intensity or the magnitude of change
      in pain intensity. LEVEL OF EVIDENCE: 2.

PMID- 27870807
TI  - Back Pain Prevalence Is Associated With Curve-type and Severity in Adolescents
      With Idiopathic Scoliosis: A Cross-sectional Study.
AB  - STUDY DESIGN: A cross-sectional study. OBJECTIVES: The aim of this study was to
      investigate spinal pain prevalence in adolescents with idiopathic scoliosis (AIS)
      and to explore associations between pain intensity and pain-related disability
      with scoliosis site, severity, and spinal bracing. SUMMARY OF BACKGROUND DATA:
      The causal link between spinal pain and AIS remains unclear. Spinal asymmetry has
      been recognized as a back pain risk factor, which is a known cause of care
      seeking in adolescents. METHODS: Participants were recruited from an outpatient
      tertiary-care scoliosis clinic. Pain intensity and pain-related disability were
      measured by the Brief Pain Inventory questionnaire and the Roland-Morris
      Disability Questionnaire. Scoliosis severity estimation was performed using Cobb
      angles. Associations were explored using multiple linear regressions and reported
      with unstandardized beta coefficients (beta) adjusted for age and sex. RESULTS:
      We recruited 500 patients (85% female) with mean (SD) age of 14.2 (1.8) years.
      Means (SD) of thoracic and lumbar Cobb angle were 24.54(9.77) and 24.13 (12.40),
      respectively. Spinal pain prevalence was 68% [95% confidence interval (95% CI):
      64.5-72.4] with a mean intensity of 1.63 (SD, 1.89). Spinal pain intensity was
      positively associated with scoliosis severity in the main thoracic (P = 0.003)
      and lumbar (P = 0.001) regions. The mean (SD) disability score was 1.73 (2.98).
      Disability was positively associated with scoliosis severity in the proximal
      thoracic (P = 0.035), main thoracic (P = 0.000), and lumbar (P = 0.000)
      regions.Spinal bracing was associated with lower spinal pain intensity in the
      thoracic (P = 0.000) and lumbar regions (P = 0.009). Bracing was also related
      with lower disability for all spinal areas (P < 0.045). CONCLUSION: Spinal pain
      is common among patients with AIS, and greater spinal deformity was associated
      with higher pain intensity. These findings should inform clinical decision-making
      when caring for patients with AIS. LEVEL OF EVIDENCE: 3.

PMID- 27870808
TI  - Description and Results of a Comprehensive Care Protocol for Overnight-Stay Spine
      Surgery in Adults.
AB  - STUDY DESIGN: This is a prospective cohort study. OBJECTIVE: The aim of this
      study was to define the probability of successful morning-after discharge after
      adult spine surgery achieved with a standard care protocol as applied to patients
      with a large variety of common degenerative spine disorders. SUMMARY OF
      BACKGROUND DATA: Qualifying criteria for ambulatory or overnight-stay adult spine
      surgery are not well defined in either the spine or anesthesia literature. Most
      reports simply go to American Society of Anesthesiology risk classification or
      surgical technique alternatives and do not present a clearly defined patient care
      and case management protocol. METHODS: A standardized protocol of patient
      preparation, preoperative comorbidities optimization, and perioperative care was
      applied in a prospective cohort of 126 patients including 83 lumbar and 41
      cervical procedures. Office and hospital chart records were reviewed for relevant
      outcomes. RESULTS: Fully 122 of 124 appropriately selected cases were able to
      successfully achieve uneventful same-day discharge without any need for
      readmission, unscheduled early emergency room or clinic visits, or other major
      complications. Both failures were for urinary retention in senior males and
      resolved after a single-day admission to the main hospital. CONCLUSION: A wide
      variety of common degenerative spinal pathology in adults can be routinely and
      safely managed on an overnight-stay basis without requirement for formal hospital
      inpatient admission in patients appropriately selected and pre-educated to the
      experience and whose major comorbidities are preoperatively optimized. LEVEL OF
      EVIDENCE: N/A.

PMID- 27870809
TI  - Rise in Haemophilus influenzae With Reduced Quinolone Susceptibility and
      Development of a Simple Screening Method.
AB  - BACKGROUND: beta-Lactamase-nonproducing ampicillin-resistant Haemophilus
      influenzae are prevalent in Japan. Resistance has increased as a consequence of
      the expanded use of antimicrobial agents, raising concerns about the rise of
      multidrug (macrolide and fluoroquinolone)-resistant H. influenzae. METHODS: In
      this study, we investigated susceptibility to fluoroquinolones in H. influenzae
      clinical isolates from 2013 to 2014 and identified the amino acid substitutions
      in quinolone resistance-determining regions of gyrA and parC. RESULTS: All
      isolates (n = 145) were susceptible to fluoroquinolones; however, some showed
      reduced susceptibility. The minimum inhibitory concentration of levofloxacin for
      these strains was 0.063-0.5 ug/mL, and the strains harbored the amino acid
      substitution S84L in GyrA. Such strains have seen a significant increase.
      Importantly, all mutants from 2014 were isolated from pediatric patients. In
      addition, we developed a simple polymerase chain reaction-based screening method
      for detecting isolates with reduced fluoroquinolone susceptibility. CONCLUSIONS:
      The mutation in GyrA is important as a first step in the development of
      fluoroquinolone resistance. Hence, detection of reduced susceptible strains may
      influence the choice of antimicrobial treatment.

PMID- 27870810
TI  - Neonatal Group B Streptococcus Infections: Prevention Strategies, Clinical and
      Microbiologic Characteristics in 7 Years of Surveillance.
AB  - BACKGROUND: The characteristics of group B streptococcus (GBS) neonatal disease
      in a period of 7 years are reported. METHODS: The estimation of the neonatal GBS
      disease risk and prevention strategies adopted at delivery in absence of national
      guidelines was evaluated by the analysis of 3501 questionnaires. Notification of
      194 neonatal GBS infections was recorded. In addition, 115 strains from neonatal
      early-onset disease (EOD) and late-onset disease, respectively, plus 320 strains
      from pregnant women were analyzed by molecular typing methods and for antibiotic
      resistance. RESULTS: Preterm deliveries, precipitous labor and GBS negatively
      screened mothers were the prominent causes for an inadequate or lack of
      intrapartum antibiotic prophylaxis and EOD occurrence. The superimposable
      serotype distribution of GBS strains from EOD and from antenatal screening
      confirmed the vertical transmission from mother to neonate as the cause of
      disease. On the contrary, late-onset disease was almost exclusively caused by the
      internationally diffused clonal complex 17. Erythromycin resistance was detected
      in 17% of strains. Resistance to clindamycin was 15.3 %. CONCLUSIONS: The
      administration of intrapartum antibiotic prophylaxis to negatively GBS screened
      women in presence of risk factors was a deviation from the recommendations issued
      by the Centers for Disease Control and Prevention, and it should deserve further
      consideration. Routine surveillance and molecular typing of circulating clones
      are essential for the effective management of the neonatal GBS disease.

PMID- 27870811
TI  - Abdominal Actinomycosis in Children: A Case Report and Literature Review.
AB  - Abdominal actinomycosis is an uncommon pediatric infection that often manifests
      with a tumor-like lesion. We describe a previously healthy 11-year-old girl who
      presented with right lower quadrant abdominal pain and drainage. Computed
      tomography scan showed an abdominal wall mass. Surgical debridement cultures grew
      Actinomyces meyeri. Literature review identified 18 additional pediatric cases
      since 1964 that we have summarized.

PMID- 27870812
TI  - Does Breastfeeding Protect Young Infants From Pertussis? Case-control Study and
      Immunologic Evaluation.
AB  - BACKGROUND: Pertussis infection can be severe in unvaccinated infants. A case
      control study was conducted to investigate the potential role of breastfeeding in
      protecting young, unvaccinated infants from pertussis. METHODS: Hospitalized
      infants <6 months of age with positive real time polymerase chain reaction for
      pertussis on nasopharyngeal aspirate were enrolled as cases; healthy controls
      were enrolled among patients admitted for ultrasound screening. Vaccinated
      infants were excluded. Sociodemographic, clinical and feeding information were
      collected. The effect of breastfeeding on pertussis was investigated through
      multivariable analysis. Breast milk and blood samples were obtained from mothers
      of patients. IgA and bacterial binding against Bordetella pertussis and other
      bacteria were tested in breast milk. IgG against pertussis toxin (PT) was tested
      in serum. RESULTS: We enrolled 296 patients (61 cases and 235 controls).
      Exclusive breastfeeding was not associated with pertussis compared with partial
      breastfeeding/artificial feeding [odds ratio: 1.2; 95% confidence interval (CI):
      0.31-4.67]. Children with siblings were at higher risk for pertussis (odds ratio:
      2.5; 95% CI: 1.21-5.35). IgA against pertussis antigens were not higher in cases
      (IgA anti-PT median = 0.24 optical density) compared with controls (IgA anti-PT
      median = 0.21 optical density). Though bacterial binding to B. pertussis,
      measured in breast milk, was higher in cases (median = 4.35%) compared with
      controls (median = 2.8%; P = 0.004), bacterial binding to B. pertussis was low
      compared with other pathogens. IgG titers were higher in mothers of cases, but no
      correlation was found between serum IgG and breast milk IgA. CONCLUSION:
      Breastfeeding remains a mainstay of prevention for numerous diseases, though it
      does not seem to play a role against pertussis. Alternative strategies to protect
      unvaccinated infants from pertussis should be considered.

PMID- 27870813
TI  - Acute Otitis Media During Infancy: Parent-reported Incidence and Modifiable Risk
      Factors.
AB  - BACKGROUND: Age at exposure to acute otitis media (AOM) risk factors such as day
      care attendance, lack of breastfeeding and tobacco smoke is little studied but
      important for targeting AOM prevention strategies. Moreover, studies are
      typically restricted to clinically diagnosed AOM, while a significant subset can
      occur outside the health care system, depending on the country setting. This
      study aims to determine risk factor exposure and effect of its timing within the
      first year of life on parent-reported AOM symptom episodes. METHODS: In the
      WHeezing and Illnesses STudy LEidsche Rijn birth-cohort study, 1056 children were
      prospectively followed during their first year of life. Group day care
      attendance, breastfeeding and tobacco smoke exposure were recorded monthly and
      parent-reported AOM symptoms daily. Generalized estimating equations were used to
      estimate the association between the time-varying risk factors and AOM symptom
      episodes, while correcting for confounding by indication. RESULTS: The first-year
      incidence rate of parent-reported AOM was 569/1000 child-years [95% confidence
      interval (CI): 523-618]. Children who attended day care had higher odds of
      developing AOM symptom episodes compared with those not attending (odds ratio:
      5.0; 95% CI: 2.6-9.6). Tobacco smoke exposure and (a history of) breastfeeding
      were not associated with AOM. Test for interaction revealed that the effect of
      day care increased with each month younger in age. CONCLUSIONS: First-year day
      care attendance is a major risk factor for AOM symptom episodes among infants in
      the community. This adjusted effect estimate is higher than previously reported
      and is age-dependent. AOM prevention strategies in day care facilities should
      therefore focus in particular on the youngest age groups.

PMID- 27870814
TI  - The Contemporary Microbiology and Rates of Concomitant Osteomyelitis in Acute
      Septic Arthritis.
AB  - BACKGROUND: Septic arthritis (SA) and acute osteomyelitis (AO) are among the most
      common serious bacterial infections of childhood. Knowledge of the microbiology
      of SA is critical to treatment. Awareness of the presence of attendant AO is also
      important to guide clinical management. We sought to describe the current
      microbiology of SA in children and clinical features associated with coexisting
      AO. MATERIALS AND METHODS: Patients with SA were identified from the infectious
      diseases consult service records from 2010 to 2014. Patients with
      penetrating/open trauma and orthopedic hardware in situ were excluded. RESULTS: A
      total of 168 patients with SA were included. The most common causative organism
      was Staphylococcus aureus accounting for 47.7% of cases (29.1% were methicillin
      susceptible S. aureus and 18.5% were methicillin-resistant S. aureus), followed
      by group A streptococcus (GAS, 8.9%). The proportion of cases due to GAS
      increased from 2011 to 2014 (3.3%-16.7%; P = 0.1). One hundred eight (64.3%)
      patients had concurrent AO. The presence of osteomyelitis was associated with
      older median age (5.9 vs. 2.4 years; P = 0.04), a longer duration of symptoms (5
      vs. 2.5 days; P < 0.001), S. aureus (62.1% vs. 21.7%; P < 0.001), bacteremia
      (46.2% vs. 20.3%; P = 0.001), a longer duration of fever after admission (5 vs. 2
      days; P < 0.001) and a longer length of stay (10 vs. 6 days; P < 0.001).
      CONCLUSIONS: Methicillin-resistant S. aureus continues to be an important cause
      of SA though GAS may be increasing in frequency. The presence of concomitant
      osteomyelitis is higher than previously reported and associated with older age, a
      longer duration of symptoms and fever, bacteremia and S. aureus.

PMID- 27870816
TI  - Welcome, Change.

PMID- 27870815
TI  - The Cape Town Clinical Decision Rule for Streptococcal Pharyngitis in Children.
AB  - BACKGROUND: Existing clinical decision rules (CDRs) to diagnose group A
      streptococcal (GAS) pharyngitis have not been validated in sub-Saharan Africa. We
      developed a locally applicable CDR while evaluating existing CDRs for diagnosing
      GAS pharyngitis in South African children. METHODS: We conducted a prospective
      cohort study and enrolled 997 children 3-15 years of age presenting to primary
      care clinics with a complaint of sore throat, and whose parents provided consent.
      Main outcome measures were signs and symptoms of pharyngitis and a positive GAS
      culture from a throat swab. Bivariate and multivariate analyses were used to
      develop the CDR. In addition, the diagnostic effectiveness of 6 existing rules
      for predicting a positive culture in our cohort was assessed. RESULTS: A total of
      206 of 982 children (21%) had a positive GAS culture. Tonsillar swelling,
      tonsillar exudates, tender or enlarged anterior cervical lymph nodes, absence of
      cough and absence of rhinorrhea were associated with positive cultures in
      bivariate and multivariate analyses. Four variables (tonsillar swelling and one
      of tonsillar exudate, no rhinorrhea, no cough), when used in a cumulative score,
      showed 83.7% sensitivity and 32.2% specificity for GAS pharyngitis. Of existing
      rules tested, the rule by McIsaac et al had the highest positive predictive value
      (28%), but missed 49% of the culture-positive children who should have been
      treated. CONCLUSION: The new 4-variable CDR for GAS pharyngitis (ie, tonsillar
      swelling and one of tonsillar exudate, no rhinorrhea, no cough) outperformed
      existing rules for GAS pharyngitis diagnosis in children with symptomatic sore
      throat in Cape Town.

PMID- 27870818
TI  - 2016 American Academy of Optometry Ocular Photography Contest.

PMID- 27870817
TI  - Clinical Pearls.

PMID- 27870819
TI  - Angiographic Characteristics of Pseudo-occlusion of the Internal Carotid Artery
      Before and After Stenting.
AB  - BACKGROUND: Various definitions of pseudo-occlusion and clinical outcomes after
      various treatments have been reported, but reports discussing the stenotic
      characteristics of pseudo-occlusion are rare. OBJECTIVE: To analyze the
      angiographic characteristics of pseudo-occlusion of the internal carotid artery
      (ICA) before and after carotid artery stenting (CAS). METHODS: We retrospectively
      reviewed the angiographic characteristics of 56 patients with pseudo-occlusion of
      the ICA treated with CAS. Angiographic changes were evaluated from digital
      subtraction angiography in terms of lesion characteristics of the stenosis and
      the diameter changes in the distal ICA before and after CAS. RESULTS: Fifty-six
      patients were successfully treated. Based on angiographic findings of ICA
      stenosis, 33 and 23 patients were classified into the single-channel and multiple
      channel group, respectively. Regarding the diameter changes in the distal ICA
      after CAS, 31 cases were classified as immediate dilatation and the other 25 as
      restricted dilatation. Immediate dilatation of the distal ICA beyond the stent
      and that at a follow-up examination were observed significantly less frequently
      in the multiple-channel group than in the single-channel group. The use of
      multiple stents and stent occlusion at a follow-up examination were significantly
      more prevalent in the multiple-channel group than in the single-channel group.
      CONCLUSION: Stenotic lesions of pseudo-occlusion of the ICA were classified as
      single channel and multiple channel. Restricted dilatation of the distal ICA
      after CAS was more prevalent in the multiple-channel group. Because adverse
      events tended to be more frequent in the multiple-channel group than in the
      single-channel group, the indications for CAS should be determined carefully in
      multiple-channel patients. ABBREVIATIONS: CAS, carotid artery stentingICA,
      internal carotid artery.

PMID- 27870820
TI  - In Reply: Can We Rely on Susceptibility-Weighted Imaging (SWI) for Subthalamic
      Nucleus Identification in Deep Brain Stimulation Surgery?

PMID- 27870822
TI  - Comparison of Total Lung Capacity Determined by Plethysmography With Computed
      Tomographic Segmentation Using CALIPER.
AB  - PURPOSE: Traditionally, determination of total lung capacity (TLC) by
      plethysmography (TLCpleth) has been important in the diagnosis of lung diseases.
      Alternatively, data acquired from computerized tomography (CT) can be utilized to
      calculate a measure of TLC (TLCCT). The clinical utility of TLCCT is not certain.
      We sought to determine, in a clinical setting, whether TLCCT correlates with
      TLCpleth across a range of lung diseases and scanning techniques. In addition, we
      determined whether TLCCT affects the interpretation of pulmonary function tests.
      SUBJECTS AND METHODS: Records of 118 of 148 consecutive lung transplant
      recipients were reviewed and determined to have coinciding pulmonary function
      tests, including plethysmography as well as volumetric chest CT performed supine
      during full inspiration. CT images acquired with a wide range of scanning
      protocols were analyzed using CALIPER, a software program for lung and trachea
      extraction from a CT volume and volumetric tissue characterization of the lung.
      Segmentation of the lung was achieved by using completely automated dynamic
      thresholding and region-growing techniques developed to extract the relatively
      low-density lung and tracheal anatomy from the CT data set without user
      intervention. RESULTS: TLCpleth and TLCCT were strongly related with a
      correlation coefficient of 0.88 (P<0.001). The efficacy of the CT-derived measure
      was not influenced by specific lung diagnoses, age, height, body mass index, or
      spirometric parameters. TLCCT did not misidentify any diagnosis of restrictive
      lung disease, nor hyperinflation. CONCLUSIONS: In a clinical setting, CT
      segmentation analysis provides a favorable determination of TLC compared with
      traditional plethysmography. The technique has general applicability across
      varying CT data acquisition protocols, lung diseases, and patient
      characteristics. TLCCT may substitute for TLCpleth in pulmonary function
      interpretation and may be preferable for some patients in whom plethysmography is
      difficult to perform, such as transplant subjects with severe pulmonary fibrosis.

PMID- 27870823
TI  - Diagnostic Yield for Cancer and Diagnostic Accuracy of Computed Tomography-guided
      Core Needle Biopsy of Subsolid Pulmonary Lesions.
AB  - PURPOSE: We aimed to determine the diagnostic yield for cancer and diagnostic
      accuracy of computed tomography-guided core needle biopsy (CTNB) in subsolid
      pulmonary lesions. MATERIALS AND METHODS: Fifty-two biopsies of 52 subsolid
      lesions in 51 patients were identified from a database of 912 lung biopsies and
      analyzed for the diagnostic yield for cancer and diagnostic accuracy of core CTNB
      diagnosis as well as complication rates. RESULTS: When indeterminate biopsy
      results were included in the analysis, the diagnostic yield for cancer was 80.8%
      and the diagnostic accuracy of core needle biopsy was 84.6% (n=52). It was 85.7%
      and 91.7%, respectively, when indeterminate results were excluded (n=48) and
      82.4% and 82.4%, respectively, for biopsies with surgical confirmation (n=17).
      Attenuation was statistically significant for diagnostic yield for cancer
      (P=0.028) and diagnostic accuracy of core needle biopsy (P=0.001) when the
      indeterminate results were excluded (n=48). Attenuation and size were not
      statistically significant for diagnostic yield for cancer and diagnostic accuracy
      of needle biopsy (n=52), and size was not statistically significant for either
      when the indeterminate results were excluded. These results were achieved without
      any major complications as per the Society of Interventional Radiology Standards
      of Practice. CONCLUSIONS: CTNB offers a high yield in establishing a
      histopathologic diagnosis of subsolid pulmonary lesions, with both ground-glass
      and solid-predominance. The pure ground-glass category of lesions requires
      further research to determine the true diagnostic yield and diagnostic accuracy
      of core needle biopsies.

PMID- 27870824
TI  - Efficacy of a Dehydrated Hydrogel Plug to Reduce Complications Associated With
      Computed Tomography-guided Percutaneous Transthoracic Needle Biopsy.
AB  - PURPOSE: The aim of the study was to determine whether a hydrogel plug, when
      placed in the needle tract after a computed tomography-guided percutaneous
      transthoracic needle lung biopsy, reduces the rate of complications. MATERIALS
      AND METHODS: This retrospective analysis included biopsies of lung lesions from
      200 consecutive patients. The first 100 consecutive biopsies made up the control
      group, in which no plug intervention was used. The next 100 consecutive biopsies
      made up the treatment group, in which a hydrogel plug was deployed through a 19-G
      coaxial needle system after 20-G core samples were obtained. RESULTS: The overall
      mean age was 64.92 years. No statistically significant differences in patient
      characteristics and procedure parameters were found between the control and
      treatment groups except for age (mean age, 62.92 vs. 66.92 y, P=0.022) and
      procedure duration (mean minutes, 7.81 vs. 6.47 min, P=0.021). The rate of
      pneumothorax in the control versus treatment group was 31% vs. 29% (P=0.498) and
      the rate of hemoptysis was 6% vs. 3% (P=0.354). The rate of chest tube insertion
      after pneumothorax was significantly higher in the control group than in the
      treatment group (10% vs. 2%, P=0.032) and the average length of hospital stay was
      longer in the control group (0.44 vs. 0.07 d, P=0.041). The difference was still
      statistically significant for the chest tube insertion rate (P=0.030) and close
      to statistically significant for the length of hospital stay (P=0.063), after
      adjusting for the confounding effect of age and procedure duration. CONCLUSION:
      These data show that the deployment of a hydrogel plug after a computed
      tomography-guided lung biopsy significantly reduced the rate of chest tube
      insertion along with a reduced length of hospital stay.

PMID- 27870825
TI  - Evaluation of Pediatric Liver Transplantation-Related Artery Complications Using
      Intra-Operative Multi-Parameter Ultrasonography.
AB  - BACKGROUND This article discusses the value of using multi-parameter evaluation
      of intra-operative ultrasonography in evaluating pediatric liver transplantation
      related arterial complications. MATERIAL AND METHODS Sixty-eight children
      receiving a liver transplant underwent intraoperative ultrasonography for
      monitoring of artery hemodynamics. The ultrasonic measurement parameters included
      the diameters of the hepatic artery (HA) of the donor and anastomotic stoma, peak
      systolic velocity (PSV), resistance index (RI), acceleration time (SAT), and
      blood flow volume. RESULTS After being treated immediately using surgery or other
      means, blood flow returned to normal in 8 cases, and did not in 3 cases, of whom
      2 experienced postoperative HAT. There was a significant difference in HA
      diameter of the donor, anastomotic stoma diameter, PSV, RI, SAT, and blood flow
      volume before and after treatment of the donor in the complications group.
      Postoperative complications occurred in 7 of 68 recipients, including the 2 cases
      exhibiting complications during the surgery (complication group) and 5 without
      complications during the surgery (no complication group). There was a
      statistically significant difference (P<0.05) between the 2 groups in
      intraoperative ultrasonography parameters of HA diameter, anastomotic stoma
      diameter, RI, and blood flow volume. CONCLUSIONS Through intraoperative multi
      parameter ultrasonic measurement, a definite diagnosis of hepatic artery
      complications can be made in liver transplantation patients. HA diameter of the
      donor, anastomotic stoma diameter, PSV, RI, SAT, and blood flow volume are
      important in assessing intraoperative artery complications.

PMID- 27870826
TI  - Development and verification of a pharmacokinetic model to optimize physiologic
      replacement of rhIGF-1/rhIGFBP-3 in preterm infants.
AB  - BACKGROUND: rhIGF-1/rhIGFBP-3 is being investigated for prevention of retinopathy
      of prematurity in extremely preterm infants. METHODS: A population
      pharmacokinetic model was developed using data from phase I/II (Sections A-C)
      trials of rhIGF-1/rhIGFBP-3 and additional studies in preterm infants to predict
      optimal dosing to establish/maintain serum IGF-1 within physiological
      intrauterine levels. In Section D of the phase II study, infants (gestational age
      (GA) (wk+d) 23+0 to 27+6) were randomized to rhIGF-1/rhIGFBP-3, administered at
      the model-predicted dose of 250 ug/kg/d continuous i.v. infusion up to
      postmenstrual age (PMA) 29 wk+6 d or standard of care. An interim pharmacokinetic
      analysis was performed for the first 10 treated infants to verify dosing.
      RESULTS: Serum IGF-1 data were reviewed for 10 treated/9 control infants.
      Duration of therapy in treated infants ranged 1-34.5 d. At baseline (before
      infusion and <24 h from birth), mean (SD) IGF-1 was 19.2 (8.0) MUg/l (treated)
      and 15.4 (4.7) MUg/l (controls). Mean (SD) IGF-1 increased to 45.9 (19.6) MUg/l
      at 12 h in treated infants, and remained within target levels for all subsequent
      timepoints. For treated infants, 88.8% of the IGF-1 measurements were within
      target levels (controls, 11.1%). CONCLUSION: Through the reported work, we
      determined appropriate rhIGF-1/rhIGFBP-3 dosing to achieve physiological
      intrauterine serum IGF-1 levels in extremely preterm infants.

PMID- 27870827
TI  - Augmented Th17-type immune responses in preterm neonates exposed to histologic
      chorioamnionitis.
AB  - BACKGROUND: Histologic chorioamnionitis (HCA) is a placental inflammatory
      disorder that frequently precedes preterm delivery. HCA increases risk for long
      standing inflammatory injury and may influence immune programming, particularly
      in preterm (PT) neonates. We hypothesized that HCA exposure is associated with an
      increased circulating frequency of proinflammatory, Th17-type responses. METHODS:
      Placental cord blood was collected from HCA-exposed or control neonates (23-41 wk
      gestation). Frequencies of Th17 and T regulatory (Treg) cells and assessments of
      Th17-type features in CD4 and Treg cells were determined by flow cytometric
      analysis. RESULTS: Cord blood samples from 31 PT and 17 term neonates were
      analyzed by flow cytometry. A diagnosis of HCA in extremely PT (EPT, GA <= 30 wk)
      gestations was associated with the highest cord blood frequencies of progenitor
      (pTh17, CD4+CD161+) and mature (mTh17, CD4+CD161+CCR6+) Th17 cells. Preterm
      neonates exposed to HCA also exhibited elevated cord blood frequencies of IL-17+
      Treg cells, as well as T cells with effector memory phenotype (TEM) that
      coexpressed Th17-type surface antigens. CONCLUSION: Th17-type responses are
      amplified in preterm neonates exposed to HCA. We speculate that a Th17 bias may
      potentiate the inflammatory responses and related morbidity observed in preterm
      neonates whose immune systems have been "primed" by HCA exposure.

PMID- 27870828
TI  - Agonist-stimulated phosphatidylinositol-3,4,5-trisphosphate generation by
      scaffolded phosphoinositide kinases.
AB  - Generation of the lipid messenger phosphatidylinositol-3,4,5-trisphosphate
      (PtdIns(3,4,5)P3) is crucial for development, cell growth and survival, and
      motility, and it becomes dysfunctional in many diseases including cancers. Here
      we reveal a mechanism for PtdIns(3,4,5)P3 generation by scaffolded
      phosphoinositide kinases. In this pathway, class I phosphatidylinositol-3-OH
      kinase (PI(3)K) is assembled by IQGAP1 with PI(4)KIIIalpha and PIPKIalpha, which
      sequentially generate PtdIns(3,4,5)P3 from phosphatidylinositol. By scaffolding
      these kinases into functional proximity, the PtdIns(4,5)P2 generated is
      selectively used by PI(3)K for PtdIns(3,4,5)P3 generation, which then signals to
      PDK1 and Akt that are also in the complex. Moreover, multiple receptor types
      stimulate the assembly of this IQGAP1-PI(3)K signalling complex. Blockade of
      IQGAP1 interaction with PIPKIalpha or PI(3)K inhibited PtdIns(3,4,5)P3 generation
      and signalling, and selectively diminished cancer cell survival, revealing a
      target for cancer chemotherapy.

PMID- 27870829
TI  - Crumbs2 promotes cell ingression during the epithelial-to-mesenchymal transition
      at gastrulation.
AB  - During gastrulation of the mouse embryo, individual cells ingress in an
      apparently stochastic pattern during the epithelial-to-mesenchymal transition
      (EMT). Here we define a critical role of the apical protein Crumbs2 (CRB2) in the
      gastrulation EMT. Static and live imaging show that ingressing cells in Crumbs2
      mutant embryos become trapped at the primitive streak, where they continue to
      express the epiblast transcription factor SOX2 and retain thin E-cadherin
      containing connections to the epiblast surface that trap them at the streak. CRB2
      is distributed in a complex anisotropic pattern on apical cell edges, and the
      level of CRB2 on a cell edge is inversely correlated with the level of myosin
      IIB. The data suggest that the distributions of CRB2 and myosin IIB define which
      cells will ingress, and we propose that cells with high apical CRB2 are basally
      extruded from the epiblast by neighbouring cells with high levels of apical
      myosin.

PMID- 27870830
TI  - Clonal fate mapping quantifies the number of haematopoietic stem cells that arise
      during development.
AB  - Haematopoietic stem cells (HSCs) arise in the developing aorta during
      embryogenesis. The number of HSC clones born has been estimated through
      transplantation, but experimental approaches to assess the absolute number of
      forming HSCs in a native setting have remained challenging. Here, we applied
      single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs.
      Targeting creERT2 in developing cd41:eGFP+ HSCs enabled long-term assessment of
      their blood contribution. We also applied the Brainbow-based multicolour Zebrabow
      system with drl:creERT2 that is active in early haematopoiesis to induce
      heritable colour barcoding unique to each HSC and its progeny. Our findings
      reveal that approximately 21 HSC clones exist prior to HSC emergence and 30
      clones are present during peak production from aortic endothelium. Our methods
      further reveal that stress haematopoiesis, including sublethal irradiation and
      transplantation, reduces clonal diversity. Our findings provide quantitative
      insights into the early clonal events that regulate haematopoietic development.

PMID- 27870832
TI  - Position effects influence HIV latency reversal.
AB  - The main obstacle to curing HIV is the presence of latent proviruses in the
      bodies of infected patients. The partial success of reactivation therapies
      suggests that the genomic context of integrated proviruses can interfere with
      treatment. Here we developed a method called Barcoded HIV ensembles (B-HIVE) to
      map the chromosomal locations of thousands of individual proviruses while
      tracking their transcriptional activities in an infected cell population. B-HIVE
      revealed that, in Jurkat cells, the expression of HIV is strongest close to
      endogenous enhancers. The insertion site also affects the response to latency
      reversing agents, because we found that phytohemagglutinin and vorinostat
      reactivated proviruses inserted at distinct genomic locations. From these
      results, we propose that combinations of drugs targeting all areas of the genome
      will be most effective. Overall, our data suggest that the insertion context of
      HIV is a critical determinant of the viral response to reactivation therapies.

PMID- 27870831
TI  - Asymmetric division coordinates collective cell migration in angiogenesis.
AB  - The asymmetric division of stem or progenitor cells generates daughters with
      distinct fates and regulates cell diversity during tissue morphogenesis. However,
      roles for asymmetric division in other more dynamic morphogenetic processes, such
      as cell migration, have not previously been described. Here we combine zebrafish
      in vivo experimental and computational approaches to reveal that heterogeneity
      introduced by asymmetric division generates multicellular polarity that drives
      coordinated collective cell migration in angiogenesis. We find that asymmetric
      positioning of the mitotic spindle during endothelial tip cell division generates
      daughters of distinct size with discrete 'tip' or 'stalk' thresholds of pro
      migratory Vegfr signalling. Consequently, post-mitotic Vegfr asymmetry drives
      Dll4/Notch-independent self-organization of daughters into leading tip or
      trailing stalk cells, and disruption of asymmetry randomizes daughter tip/stalk
      selection. Thus, asymmetric division seamlessly integrates cell proliferation
      with collective migration, and, as such, may facilitate growth of other
      collectively migrating tissues during development, regeneration and cancer
      invasion.

PMID- 27870833
TI  - Integrative classification of human coding and noncoding genes through RNA
      metabolism profiles.
AB  - Pervasive transcription of the human genome results in a heterogeneous mix of
      coding RNAs and long noncoding RNAs (lncRNAs). Only a small fraction of lncRNAs
      have demonstrated regulatory functions, thus making functional lncRNAs difficult
      to distinguish from nonfunctional transcriptional byproducts. This difficulty has
      resulted in numerous competing human lncRNA classifications that are complicated
      by a steady increase in the number of annotated lncRNAs. To address these
      challenges, we quantitatively examined transcription, splicing, degradation,
      localization and translation for coding and noncoding human genes. We observed
      that annotated lncRNAs had lower synthesis and higher degradation rates than
      mRNAs and discovered mechanistic differences explaining slower lncRNA splicing.
      We grouped genes into classes with similar RNA metabolism profiles, containing
      both mRNAs and lncRNAs to varying extents. These classes exhibited distinct RNA
      metabolism, different evolutionary patterns and differential sensitivity to
      cellular RNA-regulatory pathways. Our classification provides an alternative to
      genomic context-driven annotations of lncRNAs.

PMID- 27870836
TI  - The RNA helicase Mtr4p is a duplex-sensing translocase.
AB  - The conserved Saccharomyces cerevisiae Ski2-like RNA helicase Mtr4p plays
      essential roles in eukaryotic nuclear RNA processing. RNA helicase activity of
      Mtr4p is critical for biological functions of the enzyme, but the molecular basis
      for RNA unwinding is not understood. Here, single-molecule high-resolution
      optical trapping measurements reveal that Mtr4p unwinds RNA duplexes by 3'-to-5'
      translocation on the loading strand, that strand separation occurs in discrete
      steps of 6 base pairs and that a single Mtr4p molecule performs consecutive
      unwinding steps. We further show that RNA unwinding by Mtr4p requires interaction
      with upstream RNA duplex. Inclusion of Mtr4p within the TRAMP complex increases
      the rate constant for unwinding initiation but does not change the
      characteristics of Mtr4p's helicase mechanism. Our data indicate that Mtr4p
      utilizes a previously unknown unwinding mode that combines aspects of canonical
      translocating helicases and non-canonical duplex-sensing helicases, thereby
      restricting directional translocation to duplex regions.

PMID- 27870834
TI  - Position-dependent termination and widespread obligatory frameshifting in
      Euplotes translation.
AB  - The ribosome can change its reading frame during translation in a process known
      as programmed ribosomal frameshifting. These rare events are supported by complex
      mRNA signals. However, we found that the ciliates Euplotes crassus and Euplotes
      focardii exhibit widespread frameshifting at stop codons. 47 different codons
      preceding stop signals resulted in either +1 or +2 frameshifts, and +1
      frameshifting at AAA was the most frequent. The frameshifts showed unusual
      plasticity and rapid evolution, and had little influence on translation rates.
      The proximity of a stop codon to the 3' mRNA end, rather than its occurrence or
      sequence context, appeared to designate termination. Thus, a 'stop codon' is not
      a sufficient signal for translation termination, and the default function of stop
      codons in Euplotes is frameshifting, whereas termination is specific to certain
      mRNA positions and probably requires additional factors.

PMID- 27870835
TI  - Full antagonism of the estrogen receptor without a prototypical ligand side
      chain.
AB  - Resistance to endocrine therapies remains a major clinical problem for the
      treatment of estrogen receptor-alpha (ERalpha)-positive breast cancer. On-target
      side effects limit therapeutic compliance and use for chemoprevention,
      highlighting an unmet need for new therapies. Here we present a full-antagonist
      ligand series lacking the prototypical ligand side chain that has been
      universally used to engender antagonism of ERalpha through poorly understood
      structural mechanisms. A series of crystal structures and phenotypic assays
      reveal a structure-based design strategy with separate design elements for
      antagonism and degradation of the receptor, and access to a structurally distinct
      space for further improvements in ligand design. Understanding structural rules
      that guide ligands to produce diverse ERalpha-mediated phenotypes has broad
      implications for the treatment of breast cancer and other estrogen-sensitive
      aspects of human health including bone homeostasis, energy metabolism, and
      autoimmunity.

PMID- 27870837
TI  - Ubiquitin utilizes an acidic surface patch to alter chromatin structure.
AB  - Ubiquitylation of histone H2B, associated with gene activation, leads to
      chromatin decompaction through an unknown mechanism. We used a hydrogen-deuterium
      exchange strategy coupled with NMR spectroscopy to map the ubiquitin surface
      responsible for its structural effects on chromatin. Our studies revealed that a
      previously uncharacterized acidic patch on ubiquitin comprising residues Glu16
      and Glu18 is essential for decompaction. These residues mediate promiscuous
      electrostatic interactions with the basic histone proteins, potentially
      positioning the ubiquitin moiety as a dynamic 'wedge' that prevents the intimate
      association of neighboring nucleosomes. Using two independent crosslinking
      strategies and an oligomerization assay, we also showed that ubiquitin-ubiquitin
      contacts occur in the chromatin environment and are important for the
      solubilization of the chromatin polymers. Our work highlights a novel, chromatin
      related aspect of the 'ubiquitin code' and sheds light on how the information
      rich ubiquitin modification can orchestrate different biochemical outcomes using
      distinct surface features.

PMID- 27870839
TI  - Nanomedicine: Catching tumour cells in the zone.

PMID- 27870838
TI  - A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.
AB  - Synthetic protein switches controlled with user-defined inputs are powerful tools
      for studying and controlling dynamic cellular processes. To date, these
      approaches have relied primarily on intermolecular regulation. Here we report a
      computationally guided framework for engineering intramolecular regulation of
      protein function. We utilize this framework to develop chemically inducible
      activator of RAS (CIAR), a single-component RAS rheostat that directly activates
      endogenous RAS in response to a small molecule. Using CIAR, we show that direct
      RAS activation elicits markedly different RAS-ERK signaling dynamics from growth
      factor stimulation, and that these dynamics differ among cell types. We also
      found that the clinically approved RAF inhibitor vemurafenib potently primes
      cells to respond to direct wild-type RAS activation. These results demonstrate
      the utility of CIAR for quantitatively interrogating RAS signaling. Finally, we
      demonstrate the general utility of our approach in design of intramolecularly
      regulated protein tools by applying it to the Rho family of guanine nucleotide
      exchange factors.

PMID- 27870840
TI  - Single-nanotube tracking reveals the nanoscale organization of the extracellular
      space in the live brain.
AB  - The brain is a dynamic structure with the extracellular space (ECS) taking up
      almost a quarter of its volume. Signalling molecules, neurotransmitters and
      nutrients transit via the ECS, which constitutes a key microenvironment for
      cellular communication and the clearance of toxic metabolites. The spatial
      organization of the ECS varies during sleep, development and aging and is
      probably altered in neuropsychiatric and degenerative diseases, as inferred from
      electron microscopy and macroscopic biophysical investigations. Here we show an
      approach to directly observe the local ECS structures and rheology in brain
      tissue using super-resolution imaging. We inject single-walled carbon nanotubes
      into rat cerebroventricles and follow the near-infrared emission of individual
      nanotubes as they diffuse inside the ECS for tens of minutes in acute slices.
      Because of the interplay between the nanotube geometry and the ECS local
      environment, we can extract information about the dimensions and local viscosity
      of the ECS. We find a striking diversity of ECS dimensions down to 40 nm, and as
      well as of local viscosity values. Moreover, by chemically altering the
      extracellular matrix of the brains of live animals before nanotube injection, we
      reveal that the rheological properties of the ECS are affected, but these
      alterations are local and inhomogeneous at the nanoscale.

PMID- 27870841
TI  - Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle
      mediated magnetic ranking.
AB  - Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in
      whole blood is critical to unravelling the complex and dynamic properties of
      these potential clinical markers. This task is challenging because these cells
      are present at parts per billion levels among normal blood cells. Here we report
      a new nanoparticle-enabled method for CTC characterization, called magnetic
      ranking cytometry, which profiles CTCs on the basis of their surface expression
      phenotype. We achieve this using a microfluidic chip that successfully processes
      whole blood samples. The approach classifies CTCs with single-cell resolution in
      accordance with their expression of phenotypic surface markers, which is read out
      using magnetic nanoparticles. We deploy this new technique to reveal the dynamic
      phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth
      and aggressiveness. We also test magnetic ranking cytometry using blood samples
      collected from cancer patients.

PMID- 27870842
TI  - Probing the electronic and catalytic properties of a bimetallic surface with 3 nm
      resolution.
AB  - An atomic- and molecular-level understanding of heterogeneous catalysis is
      required to characterize the nature of active sites and improve the rational
      design of catalysts. Achieving this level of characterization requires techniques
      that can correlate catalytic performances to specific surface structures, so as
      to avoid averaging effects. Tip-enhanced Raman spectroscopy combines scanning
      probe microscopy with plasmon-enhanced Raman scattering and provides simultaneous
      topographical and chemical information at the nano/atomic scale from ambient to
      ultrahigh-vacuum and electrochemical environments. Therefore, it has been used to
      monitor catalytic reactions and is proposed to correlate the local structure and
      function of heterogeneous catalysts. Bimetallic catalysts, such as Pd-Au, show
      superior performance in various catalytic reactions, but it has remained
      challenging to correlate structure and reactivity because of their structural
      complexity. Here, we show that TERS can chemically and spatially probe the site
      specific chemical (electronic and catalytic) and physical (plasmonic) properties
      of an atomically well-defined Pd(sub-monolayer)/Au(111) bimetallic model catalyst
      at 3 nm resolution in real space using phenyl isocyanide as a probe molecule
      (Fig. 1a). We observe a weakened N=C bond and enhanced reactivity of phenyl
      isocyanide adsorbed at the Pd step edge compared with that at the Pd terrace.
      Density functional theory corroborates these observations by revealing a higher d
      band electronic profile for the low-coordinated Pd step edge atoms. The 3 nm
      spatial resolution we demonstrate here is the result of an enhanced electric
      field and distinct electronic properties at the step edges.

PMID- 27870843
TI  - High electron mobility, quantum Hall effect and anomalous optical response in
      atomically thin InSe.
AB  - A decade of intense research on two-dimensional (2D) atomic crystals has revealed
      that their properties can differ greatly from those of the parent compound. These
      differences are governed by changes in the band structure due to quantum
      confinement and are most profound if the underlying lattice symmetry changes.
      Here we report a high-quality 2D electron gas in few-layer InSe encapsulated in
      hexagonal boron nitride under an inert atmosphere. Carrier mobilities are found
      to exceed 103 cm2 V-1 s-1 and 104 cm2 V-1 s-1 at room and liquid-helium
      temperatures, respectively, allowing the observation of the fully developed
      quantum Hall effect. The conduction electrons occupy a single 2D subband and have
      a small effective mass. Photoluminescence spectroscopy reveals that the bandgap
      increases by more than 0.5 eV with decreasing the thickness from bulk to bilayer
      InSe. The band-edge optical response vanishes in monolayer InSe, which is
      attributed to the monolayer's mirror-plane symmetry. Encapsulated 2D InSe expands
      the family of graphene-like semiconductors and, in terms of quality, is
      competitive with atomically thin dichalcogenides and black phosphorus.

PMID- 27870844
TI  - Raman spectroscopy: Tipping point.

PMID- 27870845
TI  - Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical
      Analysis of Atom Transition Networks.
AB  - Conserved moieties are groups of atoms that remain intact in all reactions of a
      metabolic network. Identification of conserved moieties gives insight into the
      structure and function of metabolic networks and facilitates metabolic modelling.
      All moiety conservation relations can be represented as nonnegative integer
      vectors in the left null space of the stoichiometric matrix corresponding to a
      biochemical network. Algorithms exist to compute such vectors based only on
      reaction stoichiometry but their computational complexity has limited their
      application to relatively small metabolic networks. Moreover, the vectors
      returned by existing algorithms do not, in general, represent conservation of a
      specific moiety with a defined atomic structure. Here, we show that
      identification of conserved moieties requires data on reaction atom mappings in
      addition to stoichiometry. We present a novel method to identify conserved
      moieties in metabolic networks by graph theoretical analysis of their underlying
      atom transition networks. Our method returns the exact group of atoms belonging
      to each conserved moiety as well as the corresponding vector in the left null
      space of the stoichiometric matrix. It can be implemented as a pipeline of
      polynomial time algorithms. Our implementation completes in under five minutes on
      a metabolic network with more than 4,000 mass balanced reactions. The scalability
      of the method enables extension of existing applications for moiety conservation
      relations to genome-scale metabolic networks. We also give examples of new
      applications made possible by elucidating the atomic structure of conserved
      moieties.

PMID- 27870846
TI  - Improved Measures of Integrated Information.
AB  - Although there is growing interest in measuring integrated information in
      computational and cognitive systems, current methods for doing so in practice are
      computationally unfeasible. Existing and novel integration measures are
      investigated and classified by various desirable properties. A simple taxonomy of
      Phi-measures is presented where they are each characterized by their choice of
      factorization method (5 options), choice of probability distributions to compare
      (3 * 4 options) and choice of measure for comparing probability distributions (7
      options). When requiring the Phi-measures to satisfy a minimum of attractive
      properties, these hundreds of options reduce to a mere handful, some of which
      turn out to be identical. Useful exact and approximate formulas are derived that
      can be applied to real-world data from laboratory experiments without posing
      unreasonable computational demands.

PMID- 27870847
TI  - Creating High-Resolution Multiscale Maps of Human Tissue Using Multi-beam SEM.
AB  - Multi-beam scanning electron microscopy (mSEM) enables high-throughput, nano
      resolution imaging of macroscopic tissue samples, providing an unprecedented
      means for structure-function characterization of biological tissues and their
      cellular inhabitants, seamlessly across multiple length scales. Here we describe
      computational methods to reconstruct and navigate a multitude of high-resolution
      mSEM images of the human hip. We calculated cross-correlation shift vectors
      between overlapping images and used a mass-spring-damper model for optimal global
      registration. We utilized the Google Maps API to create an interactive map and
      provide open access to our reconstructed mSEM datasets to both the public and
      scientific communities via our website www.mechbio.org. The nano- to macro-scale
      map reveals the tissue's biological and material constituents. Living inhabitants
      of the hip bone (e.g. osteocytes) are visible in their local extracellular matrix
      milieu (comprising collagen and mineral) and embedded in bone's structural tissue
      architecture, i.e. the osteonal structures in which layers of mineralized tissue
      are organized in lamellae around a central blood vessel. Multi-beam SEM and our
      presented methodology enable an unprecedented, comprehensive understanding of
      health and disease from the molecular to organ length scale.

PMID- 27870848
TI  - Genetically Blocking the Zebrafish Pineal Clock Affects Circadian Behavior.
AB  - The master circadian clock in fish has been considered to reside in the pineal
      gland. This dogma is challenged, however, by the finding that most zebrafish
      tissues contain molecular clocks that are directly reset by light. To further
      examine the role of the pineal gland oscillator in the zebrafish circadian
      system, we generated a transgenic line in which the molecular clock is
      selectively blocked in the melatonin-producing cells of the pineal gland by a
      dominant-negative strategy. As a result, clock-controlled rhythms of melatonin
      production in the adult pineal gland were disrupted. Moreover, transcriptome
      analysis revealed that the circadian expression pattern of the majority of clock
      controlled genes in the adult pineal gland is abolished. Importantly, circadian
      rhythms of behavior in zebrafish larvae were affected: rhythms of place
      preference under constant darkness were eliminated, and rhythms of locomotor
      activity under constant dark and constant dim light conditions were markedly
      attenuated. On the other hand, global peripheral molecular oscillators, as
      measured in whole larvae, were unaffected in this model. In conclusion,
      characterization of this novel transgenic model provides evidence that the
      molecular clock in the melatonin-producing cells of the pineal gland plays a key
      role, possibly as part of a multiple pacemaker system, in modulating circadian
      rhythms of behavior.

PMID- 27870849
TI  - Phosphorylation of CBP20 Links MicroRNA to Root Growth in the Ethylene Response.
AB  - Ethylene is one of the most important hormones for plant developmental processes
      and stress responses. However, the phosphorylation regulation in the ethylene
      signaling pathway is largely unknown. Here we report the phosphorylation of cap
      binding protein 20 (CBP20) at Ser245 is regulated by ethylene, and the
      phosphorylation is involved in root growth. The constitutive phosphorylation
      mimic form of CBP20 (CBP20S245E or CBP20S245D), while not the constitutive de
      phosphorylation form of CBP20 (CBP20S245A) is able to rescue the root ethylene
      responsive phenotype of cbp20. By genome wide study with ethylene regulated gene
      expression and microRNA (miRNA) expression in the roots and shoots of both Col-0
      and cbp20, we found miR319b is up regulated in roots while not in shoots, and its
      target MYB33 is specifically down regulated in roots with ethylene treatment. We
      described both the phenotypic and molecular consequences of transgenic over
      expression of miR319b. Increased levels of miR319b (miR319bOE) leads to enhanced
      ethylene responsive root phenotype and reduction of MYB33 transcription level in
      roots; over expression of MYB33, which carrying mutated miR319b target site
      (mMYB33) in miR319bOE is able to recover both the root phenotype and the
      expression level of MYB33. Taken together, we proposed that ethylene regulated
      phosphorylation of CBP20 is involved in the root growth and one pathway is
      through the regulation of miR319b and its target MYB33 in roots.

PMID- 27870850
TI  - A Biophysical Systems Approach to Identifying the Pathways of Acute and Chronic
      Doxorubicin Mitochondrial Cardiotoxicity.
AB  - The clinical use of the anthracycline doxorubicin is limited by its
      cardiotoxicity which is associated with mitochondrial dysfunction. Redox cycling,
      mitochondrial DNA damage and electron transport chain inhibition have been
      identified as potential mechanisms of toxicity. However, the relative roles of
      each of these proposed mechanisms are still not fully understood. The purpose of
      this study is to identify which of these pathways independently or in combination
      are responsible for doxorubicin toxicity. A state of the art mathematical model
      of the mitochondria including the citric acid cycle, electron transport chain and
      ROS production and scavenging systems was extended by incorporating a novel
      representation for mitochondrial DNA damage and repair. In silico experiments
      were performed to quantify the contributions of each of the toxicity mechanisms
      to mitochondrial dysfunction during the acute and chronic stages of toxicity.
      Simulations predict that redox cycling has a minor role in doxorubicin
      cardiotoxicity. Electron transport chain inhibition is the main pathway for acute
      toxicity for supratherapeutic doses, being lethal at mitochondrial concentrations
      higher than 200MUM. Direct mitochondrial DNA damage is the principal pathway of
      chronic cardiotoxicity for therapeutic doses, leading to a progressive and
      irreversible long term mitochondrial dysfunction.

PMID- 27870852
TI  - Order Under Uncertainty: Robust Differential Expression Analysis Using
      Probabilistic Models for Pseudotime Inference.
AB  - Single cell gene expression profiling can be used to quantify transcriptional
      dynamics in temporal processes, such as cell differentiation, using computational
      methods to label each cell with a 'pseudotime' where true time series
      experimentation is too difficult to perform. However, owing to the high
      variability in gene expression between individual cells, there is an inherent
      uncertainty in the precise temporal ordering of the cells. Pre-existing methods
      for pseudotime estimation have predominantly given point estimates precluding a
      rigorous analysis of the implications of uncertainty. We use probabilistic
      modelling techniques to quantify pseudotime uncertainty and propagate this into
      downstream differential expression analysis. We demonstrate that reliance on a
      point estimate of pseudotime can lead to inflated false discovery rates and that
      probabilistic approaches provide greater robustness and measures of the temporal
      resolution that can be obtained from pseudotime inference.

PMID- 27870851
TI  - A Normalization Framework for Emotional Attention.
AB  - The normalization model of attention proposes that attention can affect
      performance by response- or contrast-gain changes, depending on the size of the
      stimulus and attention field. Here, we manipulated the attention field by
      emotional valence, negative faces versus positive faces, while holding stimulus
      size constant in a spatial cueing task. We observed changes in the cueing effect
      consonant with changes in response gain for negative faces and contrast gain for
      positive faces. Neuroimaging experiments confirmed that subjects' attention
      fields were narrowed for negative faces and broadened for positive faces.
      Importantly, across subjects, the self-reported emotional strength of negative
      faces and positive faces correlated, respectively, both with response- and
      contrast-gain changes and with primary visual cortex (V1) narrowed and broadened
      attention fields. Effective connectivity analysis showed that the emotional
      valence-dependent attention field was closely associated with feedback from the
      dorsolateral prefrontal cortex (DLPFC) to V1. These findings indicate a crucial
      involvement of DLPFC in the normalization processes of emotional attention.

PMID- 27870854
TI  - Quantity and/or Quality? The Importance of Publishing Many Papers.
AB  - Do highly productive researchers have significantly higher probability to produce
      top cited papers? Or do high productive researchers mainly produce a sea of
      irrelevant papers-in other words do we find a diminishing marginal result from
      productivity? The answer on these questions is important, as it may help to
      answer the question of whether the increased competition and increased use of
      indicators for research evaluation and accountability focus has perverse effects
      or not. We use a Swedish author disambiguated dataset consisting of 48.000
      researchers and their WoS-publications during the period of 2008-2011 with
      citations until 2014 to investigate the relation between productivity and
      production of highly cited papers. As the analysis shows, quantity does make a
      difference.

PMID- 27870853
TI  - Intron Lariat RNA Inhibits MicroRNA Biogenesis by Sequestering the Dicing Complex
      in Arabidopsis.
AB  - Lariat RNAs formed as by-products of splicing are quickly degraded by the RNA
      debranching enzyme 1 (DBR1), leading to their turnover. Null dbr1 mutants in both
      animals and plants are embryo lethal, but the mechanism underlying the lethality
      remains unclear. Here we characterized a weak mutant allele of DBR1 in
      Arabidopsis, dbr1-2, and showed that a global increase in lariat RNAs was
      unexpectedly accompanied by a genome-wide reduction in miRNA accumulation. The
      dbr1-2 mutation had no effects on expression of miRNA biogenesis genes or primary
      miRNAs (pri-miRNAs), but the association of pri-miRNAs with the DCL1/HYL1 dicing
      complex was impaired. Lariat RNAs were associated with the DCL1/HYL1 dicing
      complex in vivo and competitively inhibited the binding of HYL1 with pri-miRNA.
      Consistent with the impacts of lariat RNAs on miRNA biogenesis, over-expression
      of lariat RNAs reduced miRNA accumulation. Lariat RNAs localized in nuclear
      bodies, and partially co-localize with HYL1, and both DCL1 and HYL1 were mis
      localized in dbr1-2. Together with our findings that nearly four hundred lariat
      RNAs exist in wild type plants and that these lariat RNAs also associate with the
      DCL1/HYL1 dicing complex in vivo, we thus propose that lariat RNAs, as decoys,
      inhibit miRNA processing, suggesting a hitherto unknown layer of regulation in
      miRNA biogenesis.

PMID- 27870855
TI  - Host-Parasite Interactions and Population Dynamics of Rock Ptarmigan.
AB  - Populations of rock ptarmigan (Lagopus muta) in Iceland fluctuate in multiannual
      cycles with peak numbers c. every 10 years. We studied the ptarmigan-parasite
      community and how parasites relate to ptarmigan age, body condition, and
      population density. We collected 632 ptarmigan in northeast Iceland in early
      October from 2006 to 2012; 630 (99.7%) were infected with at least one parasite
      species, 616 (98%) with ectoparasites, and 536 (85%) with endoparasites. We
      analysed indices for the combined parasite community (16 species) and known
      pathogenic parasites, two coccidian protozoans Eimeria muta and Eimeria rjupa,
      two nematodes Capillaria caudinflata and Trichostrongylus tenuis, one chewing
      louse Amyrsidea lagopi, and one skin mite Metamicrolichus islandicus. Juveniles
      overall had more ectoparasites than adults, but endoparasite levels were similar
      in both groups. Ptarmigan population density was associated with endoparasites,
      and in particular prevalence of the coccidian parasite Eimeria muta. Annual
      aggregation level of this eimerid fluctuated inversely with prevalence, with lows
      at prevalence peak and vice versa. Both prevalence and aggregation of E. muta
      tracked ptarmigan population density with a 1.5 year time lag. The time lag could
      be explained by the host specificity of this eimerid, host density dependent
      shedding of oocysts, and their persistence in the environment from one year to
      the next. Ptarmigan body condition was negatively associated with E. muta
      prevalence, an indication of their pathogenicity, and this eimerid was also
      positively associated with ptarmigan mortality and marginally inversely with
      fecundity. There were also significant associations between fecundity and chewing
      louse Amyrsidea lagopi prevalence (negative), excess juvenile mortality and
      nematode Capillaria caudinflata prevalence (positive), and adult mortality and
      skin mite Metamicrolichus islandicus prevalence (negative). Though this study is
      correlational, it provides strong evidence that E. muta through time-lag in
      prevalence with respect to host population size and by showing significant
      relations with host body condition, mortality, and fecundity could destabilize
      ptarmigan population dynamics in Iceland.

PMID- 27870857
TI  - Life-History Traits of Macrolophus pygmaeus with Different Prey Foods.
AB  - Macrolophus pygmaeus Rambur (Hemiptera: Miridae) is a generalist predatory mirid
      widely used in augmentative biological control of various insect pests in
      greenhouse tomato production in Europe, including the invasive tomato leafminer,
      Tuta absoluta (Meyrick) (Lepidoptera, Gelechiidae). However, its biocontrol
      efficacy often relies on the presence of alternative prey. The present study
      aimed at evaluating the effect of various prey foods (Ephestia kuehniella eggs,
      Bemisia tabaci nymphs, Tuta absoluta eggs and Macrosiphum euphorbiae nymphs) on
      some life history traits of M. pygmaeus. Both nymphal development and adult
      fertility of M. pygmaeus were significantly affected by prey food type, but not
      survival. Duration of nymphal stage was higher when M. pygmaeus fed on T.
      absoluta eggs compared to the other prey. Mean fertility of M. pygmaeus females
      was greatest when fed with B. tabaci nymphs, and was greater when offered M.
      euphorbiae aphids and E. kuehniella eggs than when offered T. absoluta eggs.
      Given the low quality of T. absoluta eggs, the efficacy of M. pygmaeus to control
      T. absoluta may be limited in the absence of other food sources. Experiments for
      assessing effectiveness of generalist predators should involve the possible
      impact of prey preference as well as a possible prey switching.

PMID- 27870856
TI  - Dietary Intake Influences Adult Fertility and Offspring Fitness in Zebrafish.
AB  - The burden of malnutrition, including both over- and undernutrition, is a major
      public health concern. Here we used a zebrafish model of diet-induced obesity to
      analyze the impact of dietary intake on fertility and the phenotype of the next
      generation. Over an eight-week period, one group received 60 mg of food each day
      (60 mg arm), while another received 5 mg (5 mg arm). At the end of the diet, the
      body mass index of the 60 mg arm was 1.5 fold greater than the 5 mg arm. The
      intervention also had a marked impact on fertility; breeding success and egg
      production in the 60 mg arm were increased 2.1- and 6.2-fold compared to the 5 mg
      arm, respectively. Transcriptome analysis of eggs revealed that transcripts
      involved in metabolic biological processes differed according to dietary intake.
      The progeny from the differentially fed fish were more likely to survive when the
      parents had access to more food. An intergenerational crossover study revealed
      that while parental diet did not influence weight gain in the offspring, the
      progeny of well-fed parents had increased levels of physical activity when
      exposed again to high nutrient availability. We conclude that dietary intake has
      an important influence on fertility and the subsequent fitness of offspring, even
      prior to breeding.

PMID- 27870858
TI  - First Report of the Occurrence of Trichinella-Specific Antibodies in Domestic
      Pigs in Central and Eastern Uganda.
AB  - Previous research on trichinellosis in Africa focused on isolating Trichinella
      from wildlife while the role of domestic pigs has remained highly under
      researched. Pig keeping in Uganda is historically recent, and evidence on
      zoonotic pig diseases, including infection with Trichinella species, is scarce. A
      cross-sectional survey on Trichinella seroprevalence in pigs was conducted in
      three districts in Central and Eastern Uganda from April 2013 to January 2015.
      Serum from a random sample of 1125 pigs from 22 villages in Eastern and Central
      Uganda was examined to detect immunoglobulin G (IgG) against any Trichinella spp.
      using a commercially available ELISA based on excretory-secretory antigen. ELISA
      positive samples were confirmed using Western Blot based on somatic antigen of
      Trichinella spiralis as recommended in previous validation studies. Diaphragm
      pillar muscle samples (at least 5 g each) of 499 pigs from areas with high ELISA
      positivity were examined using the artificial digestion method. Overall, 78 of
      all 1125 animals (6.9%, 95% CI: 5.6-8.6%) tested positive for antibodies against
      Trichinella spp. in the ELISA at significantly higher levels in Kamuli district
      compared to Masaka and Mukono districts. Thirty-one percent of the ELISA positive
      samples were confirmed IgG positive by the Western Blot leading to an overall
      seroprevalence of 2.1% (95% CI: 1.4-3.2%). The large proportion of ELISA positive
      samples that could not be confirmed using Western blot may be the result of cross
      reactivity with other gastrointestinal helminth infections or unknown host
      specific immune response mechanisms in local pig breeds in Uganda. Attempts to
      isolate muscle larvae for species determination using the artificial digestion
      method were unsuccessful. Due to the large number of muscle samples examined we
      are confident that even if pigs are infected, the larval burden in pork is too
      low to pose a major risk to consumers of developing trichinellosis. This was the
      first large systematic field investigation of Trichinella infection in domestic
      pigs in Uganda and its results imply that further studies are needed to identify
      the Trichinella species involved, and to identify potential sources of infection
      for humans.

PMID- 27870859
TI  - Plant Distribution Data Show Broader Climatic Limits than Expert-Based Climatic
      Tolerance Estimates.
AB  - BACKGROUND: Although increasingly sophisticated environmental measures are being
      applied to species distributions models, the focus remains on using climatic data
      to provide estimates of habitat suitability. Climatic tolerance estimates based
      on expert knowledge are available for a wide range of plants via the USDA PLANTS
      database. We aim to test how climatic tolerance inferred from plant distribution
      records relates to tolerance estimated by experts. Further, we use this
      information to identify circumstances when species distributions are more likely
      to approximate climatic tolerance. METHODS: We compiled expert knowledge
      estimates of minimum and maximum precipitation and minimum temperature tolerance
      for over 1800 conservation plant species from the 'plant characteristics'
      information in the USDA PLANTS database. We derived climatic tolerance from
      distribution data downloaded from the Global Biodiversity and Information
      Facility (GBIF) and corresponding climate from WorldClim. We compared expert
      derived climatic tolerance to empirical estimates to find the difference between
      their inferred climate niches (DeltaCN), and tested whether DeltaCN was
      influenced by growth form or range size. RESULTS: Climate niches calculated from
      distribution data were significantly broader than expert-based tolerance
      estimates (Mann-Whitney p values << 0.001). The average plant could tolerate 24
      mm lower minimum precipitation, 14 mm higher maximum precipitation, and 7 degrees
      C lower minimum temperatures based on distribution data relative to expert-based
      tolerance estimates. Species with larger ranges had greater DeltaCN for minimum
      precipitation and minimum temperature. For maximum precipitation and minimum
      temperature, forbs and grasses tended to have larger DeltaCN while grasses and
      trees had larger DeltaCN for minimum precipitation. CONCLUSION: Our results show
      that distribution data are consistently broader than USDA PLANTS experts'
      knowledge and likely provide more robust estimates of climatic tolerance,
      especially for widespread forbs and grasses. These findings suggest that widely
      available expert-based climatic tolerance estimates underrepresent species'
      fundamental niche and likely fail to capture the realized niche.

PMID- 27870860
TI  - Gene Expression Profile of High IFN-gamma Producers Stimulated with Leishmania
      braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis.
AB  - BACKGROUND: The initial response to Leishmania parasites is essential in
      determining disease development or resistance. In vitro, a divergent response to
      Leishmania, characterized by high or low IFN-gamma production has been described
      as a potential tool to predict both vaccine response and disease susceptibility
      in vivo. METHODS AND FINDINGS: We identified uninfected and healthy individuals
      that were shown to be either high- or low IFN-gamma producers (HPs and LPs,
      respectively) following stimulation of peripheral blood cells with Leishmania
      braziliensis. Following stimulation, RNA was processed for gene expression
      analysis using immune gene arrays. Both HPs and LPs were shown to upregulate the
      expression of CXCL10, IFI27, IL6 and LTA. Genes expressed in HPs only (CCL7, IL8,
      IFI44L and IL1B) were associated with pathways related to IL17 and TREM 1
      signaling. In LPs, uniquely expressed genes (for example IL9, IFI44, IFIT1 and
      IL2RA) were associated with pathways related to pattern recognition receptors and
      interferon signaling. We then investigated whether the unique gene expression
      profiles described here could be recapitulated in vivo, in individuals with
      active Cutaneous Leishmaniasis or with subclinical infection. Indeed, using a set
      of six genes (TLR2, JAK2, IFI27, IFIT1, IRF1 and IL6) modulated in HPs and LPs,
      we could successfully discriminate these two clinical groups. Finally, we
      demonstrate that these six genes are significantly overexpressed in CL lesions.
      CONCLUSION: Upon interrogation of the peripheral response of naive individuals
      with diverging IFN-gamma production to L. braziliensis, we identified differences
      in the innate response to the parasite that are recapitulated in vivo and that
      discriminate CL patients from individuals presenting a subclinical infection.

PMID- 27870861
TI  - Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol:
      Biophysical Investigations.
AB  - We report here interesting synergistic effects of proline and sorbitol, two well
      known chemical chaperones, in the inhibition of fibrillation of two proteins,
      insulin and lysozyme. A combination of many biophysical techniques has been used
      to understand the structural morphology and modes of interaction of the
      chaperones with the proteins during fibrillation. Both the chaperones establish
      stronger polar interactions in the elongation and saturation stages of
      fibrillation compared to that in the native stage. However, when presented as a
      mixture, we also see contribution of hydrophobic interactions. Thus, a co
      operative adjustment of polar and hydrophobic interactions between the chaperones
      and the protein surface seems to drive the synergistic effects in the
      fibrillation process. In insulin, this synergy is quantitatively similar in all
      the stages of the fibrillation process. These observations would have significant
      implications for understanding protein folding concepts, in general, and for
      designing combination therapies against protein fibrillation, in particular.

PMID- 27870862
TI  - Problematic Peer Functioning in Girls with ADHD: A Systematic Literature Review.
AB  - OBJECTIVE: Children with attention deficit hyperactivity disorder (ADHD)
      experience many peer interaction problems and are at risk of peer rejection and
      victimisation. Although many studies have investigated problematic peer
      functioning in children with ADHD, this research has predominantly focused on
      boys and studies investigating girls are scant. Those studies that did examine
      girls, often used a male comparison sample, disregarding the inherent gender
      differences between girls and boys. Previous studies have highlighted this
      limitation and recommended the need for comparisons between ADHD females and
      typical females, in order to elucidate the picture of female ADHD with regards to
      problematic peer functioning. The aim of this literature review was to gain
      insight into peer functioning difficulties in school-aged girls with ADHD.
      METHODS: PsychINFO, PubMed, and Web of Knowledge were searched for relevant
      literature comparing school-aged girls with ADHD to typically developing girls
      (TDs) in relation to peer functioning. The peer relationship domains were grouped
      into 'friendship', 'peer status', 'social skills/competence', and 'peer
      victimisation and bullying'. In total, thirteen studies were included in the
      review. RESULTS: All of the thirteen studies included reported that girls with
      ADHD, compared to TD girls, demonstrated increased difficulties in the domains of
      friendship, peer interaction, social skills and functioning, peer victimization
      and externalising behaviour. Studies consistently showed small to medium effects
      for lower rates of friendship participation and stability in girls with ADHD
      relative to TD girls. Higher levels of peer rejection with small to large effect
      sizes were reported in all studies, which were predicted by girls' conduct
      problems. Peer rejection in turn predicted poor social adjustment and a host of
      problem behaviours. Very high levels of peer victimisation were present in girls
      with ADHD with large effect sizes. Further, very high levels of social impairment
      and social skills deficits, with large effect sizes, were found across all
      studies. Levels of pro-social behaviour varied across studies, but were mostly
      lower in girls with ADHD, with small to large effect sizes. Overall, social
      disability was significantly higher among girls with ADHD than among TD girls.
      CONCLUSION: Congruous evidence was found for peer functioning difficulties in the
      peer relationship domains of friendship, peer status, social skills/competence,
      and peer victimisation and bullying in girls with ADHD.

PMID- 27870865
TI  - Land Use, Yield and Quality Changes of Minor Field Crops: Is There Superseded
      Potential to Be Reinvented in Northern Europe?
AB  - Diversification of agriculture was one of the strengthened aims of the greening
      payment of European Agricultural Policy (CAP) as diversification provides
      numerous ecosystems services compared to cereal-intensive crop rotations. This
      study focuses on current minor crops in Finland that have potential for expanded
      production and considers changes in their cropping areas, yield trends, breeding
      gains, roles in crop rotations and potential for improving resilience. Long-term
      datasets of Natural Resources Institute Finland and farmers' land use data from
      the Agency of Rural Affairs were used to analyze the above-mentioned trends and
      changes. The role of minor crops in rotations declined when early and late CAP
      periods were compared and that of cereal monocultures strengthened. Genetic yield
      potentials of minor crops have increased as also genetic improvements in quality
      traits, although some typical trade-offs with improved yields have also appeared.
      However, the gap between potential and attained yields has expanded, depending on
      the minor crop, as national yield trends have either stagnated or declined. When
      comparing genetic improvements of minor crops to those of the emerging major
      crop, spring wheat, breeding achievements in minor crops were lower. It was
      evident that the current agricultural policies in the prevailing market and the
      price environment have not encouraged cultivation of minor crops but further
      strengthened the role of cereal monocultures. We suggest optimization of
      agricultural land use, which is a core element of sustainable intensification, as
      a future means to couple long-term environmental sustainability with better
      success in economic profitability and social acceptability. This calls for
      development of effective policy instruments to support farmer's diversification
      actions.

PMID- 27870864
TI  - Flood-Induced Changes in Soil Microbial Functions as Modified by Plant Diversity.
AB  - Flooding frequency is predicted to increase during the next decades, calling for
      a better understanding of impacts on terrestrial ecosystems and for developing
      strategies to mitigate potential damage. Plant diversity is expected to buffer
      flooding effects by providing a broad range of species' responses. Here we report
      on the response of soil processes to a severe summer flood in 2013, which
      affected major parts of central Europe. We compared soil microbial respiration,
      biomass, nutrient limitation and enzyme activity in a grassland biodiversity
      experiment in Germany before flooding, one week and three months after the flood.
      Microbial biomass was reduced in the severely flooded plots at high, but not at
      low plant functional group richness. Flooding alleviated microbial nitrogen
      limitation, presumably due the input of nutrient-rich sediments. Further, the
      activity of soil enzymes including 1,4-beta-N-acetylglucosaminidase, phenol
      oxidase and peroxidase increased with flooding severity, suggesting increased
      chitin and lignin degradation as a consequence of the input of detritus in
      sediments. Flooding effects were enhanced at higher plant diversity, indicating
      that plant diversity temporarily reduces stability of soil processes during
      flooding. The long-term impacts, however, remain unknown and deserve further
      investigation.

PMID- 27870863
TI  - Characteristics of Aspergillus fumigatus in Association with Stenotrophomonas
      maltophilia in an In Vitro Model of Mixed Biofilm.
AB  - BACKGROUND: Biofilms are communal structures of microorganisms that have long
      been associated with a variety of persistent infections poorly responding to
      conventional antibiotic or antifungal therapy. Aspergillus fumigatus fungus and
      Stenotrophomonas maltophilia bacteria are examples of the microorganisms that can
      coexist to form a biofilm especially in the respiratory tract of
      immunocompromised patients or cystic fibrosis patients. The aim of the present
      study was to develop and assess an in vitro model of a mixed biofilm associating
      S. maltophilia and A. fumigatus by using analytical and quantitative approaches.
      MATERIALS AND METHODS: An A. fumigatus strain (ATCC 13073) expressing a Green
      Fluorescent Protein (GFP) and an S. maltophilia strain (ATCC 13637) were used.
      Fungal and bacterial inocula (105 conidia/mL and 106 cells/mL, respectively) were
      simultaneously deposited to initiate the development of an in vitro mixed biofilm
      on polystyrene supports at 37 degrees C for 24 h. The structure of the biofilm
      was analysed via qualitative microscopic techniques like scanning electron and
      transmission electron microscopy, and fluorescence microscopy, and by
      quantitative techniques including qPCR and crystal violet staining. RESULTS:
      Analytic methods revealed typical structures of biofilm with production of an
      extracellular matrix (ECM) enclosing fungal hyphae and bacteria. Quantitative
      methods showed a decrease of A. fumigatus growth and ECM production in the mixed
      biofilm with antibiosis effect of the bacteria on the fungi seen as abortive
      hyphae, limited hyphal growth, fewer conidia, and thicker fungal cell walls.
      CONCLUSION: For the first time, a mixed A. fumigatus-S. maltophilia biofilm was
      validated by various analytical and quantitative approaches and the bacterial
      antibiosis effect on the fungus was demonstrated. The mixed biofilm model is an
      interesting experimentation field to evaluate efficiency of antimicrobial agents
      and to analyse the interactions between the biofilm and the airways epithelium.

PMID- 27870866
TI  - Investigating the Predictive Value of Functional MRI to Appetitive and Aversive
      Stimuli: A Pattern Classification Approach.
AB  - BACKGROUND: Dysfunctional neural responses to appetitive and aversive stimuli
      have been investigated as possible biomarkers for psychiatric disorders. However
      it is not clear to what degree these are separate processes across the brain or
      in fact overlapping systems. To help clarify this issue we used Gaussian process
      classifier (GPC) analysis to examine appetitive and aversive processing in the
      brain. METHOD: 25 healthy controls underwent functional MRI whilst seeing
      pictures and receiving tastes of pleasant and unpleasant food. We applied GPCs to
      discriminate between the appetitive and aversive sights and tastes using
      functional activity patterns. RESULTS: The diagnostic accuracy of the GPC for the
      accuracy to discriminate appetitive taste from neutral condition was 86.5%
      (specificity = 81%, sensitivity = 92%, p = 0.001). If a participant experienced
      neutral taste stimuli the probability of correct classification was 92. The
      accuracy to discriminate aversive from neutral taste stimuli was 82.5%
      (specificity = 73%, sensitivity = 92%, p = 0.001) and appetitive from aversive
      taste stimuli was 73% (specificity = 77%, sensitivity = 69%, p = 0.001). In the
      sight modality, the accuracy to discriminate appetitive from neutral condition
      was 88.5% (specificity = 85%, sensitivity = 92%, p = 0.001), to discriminate
      aversive from neutral sight stimuli was 92% (specificity = 92%, sensitivity =
      92%, p = 0.001), and to discriminate aversive from appetitive sight stimuli was
      63.5% (specificity = 73%, sensitivity = 54%, p = 0.009). CONCLUSIONS: Our results
      demonstrate the predictive value of neurofunctional data in discriminating
      emotional and neutral networks of activity in the healthy human brain. It would
      be of interest to use pattern recognition techniques and fMRI to examine network
      dysfunction in the processing of appetitive, aversive and neutral stimuli in
      psychiatric disorders. Especially where problems with reward and punishment
      processing have been implicated in the pathophysiology of the disorder.

PMID- 27870867
TI  - Preserving Posterior Complex Can Prevent Adjacent Segment Disease following
      Posterior Lumbar Interbody Fusion Surgeries: A Finite Element Analysis.
AB  - OBJECTIVE: To investigate the biomechanical effects of the lumbar posterior
      complex on the adjacent segments after posterior lumbar interbody fusion (PLIF)
      surgeries. METHODS: A finite element model of the L1-S1 segment was modified to
      simulate PLIF with total laminectomy (PLIF-LAM) and PLIF with hemilaminectomy
      (PLIF-HEMI) procedures. The models were subjected to a 400N follower load with a
      7.5-N.m moment of flexion, extension, torsion, and lateral bending. The range of
      motion (ROM), intradiscal pressure (IDP), and ligament force were compared.
      RESULTS: In Flexion, the ROM, IDP and ligament force of posterior longitudinal
      ligament, intertransverse ligament, and capsular ligament remarkably increased at
      the proximal adjacent segment in the PLIF-LAM model, and slightly increased in
      the PLIF-HEMI model. There was almost no difference for the ROM, IDP and ligament
      force at L5-S1 level between the two PLIF models although the ligament forces of
      ligamenta flava remarkably increased compared with the intact lumbar spine (INT)
      model. For the other loading conditions, these two models almost showed no
      difference in ROM, IDP and ligament force on the adjacent discs. CONCLUSIONS:
      Preserved posterior complex acts as the posterior tension band during PLIF
      surgery and results in less ROM, IDP and ligament forces on the proximal adjacent
      segment in flexion. Preserving the posterior complex during decompression can be
      effective on preventing adjacent segment degeneration (ASD) following PLIF
      surgeries.

PMID- 27870868
TI  - Exploring Canadian Echinoderm Diversity through DNA Barcodes.
AB  - DNA barcoding has proven an effective tool for species identification in varied
      groups of marine invertebrates including crustaceans, molluscs, polychaetes and
      echinoderms. In this study, we further validate its utility by analyzing almost
      half of the 300 species of Echinodermata known from Canadian waters. COI
      sequences from 999 specimens were assigned to 145 BINs. In most cases, species
      discrimination was straightforward due to the large difference (25-fold) between
      mean intra- (0.48%) and inter- (12.0%) specific divergence. Six species were
      flagged for further taxonomic investigation because specimens assigned to them
      fell into two or three discrete sequence clusters. The potential influence of
      larval dispersal capacity and glacial events on patterns of genetic diversity is
      discussed for 19 trans-oceanic species. Although additional research is needed to
      clarify biogeographic patterns and resolve taxonomic questions, this study
      represents an important step in the assembly of a DNA barcode library for all
      Canadian echinoderms, a valuable resource for future biosurveillance programs.

PMID- 27870869
TI  - Glucose Starvation Alters Heat Shock Response, Leading to Death of Wild Type
      Cells and Survival of MAP Kinase Signaling Mutant.
AB  - A moderate heat shock induces Neurospora crassa to synthesize large quantities of
      heat shock proteins that are protective against higher, otherwise lethal
      temperatures. However, wild type cells do not survive when carbohydrate
      deprivation is added to heat shock. In contrast, a mutant strain defective in a
      stress-activated protein kinase does survive the combined stresses. In order to
      understand the basis for this difference in survival, we have determined the
      relative levels of detected proteins in the mutant and wild type strain during
      dual stress, and we have identified gene transcripts in both strains whose
      quantities change in response to heat shock or dual stress. These data and
      supportive experimental evidence point to reasons for survival of the mutant
      strain. By using alternative respiratory mechanisms, these cells experience less
      of the oxidative stress that proves damaging to wild type cells. Of central
      importance, mutant cells recycle limited resources during dual stress by
      undergoing autophagy, a process that we find utilized by both wild type and
      mutant cells during heat shock. Evidence points to inappropriate activation of
      TORC1, the central metabolic regulator, in wild type cells during dual stress,
      based upon behavior of an additional signaling mutant and inhibitor studies.

PMID- 27870870
TI  - Epidemiologic Correlates of Mortality among Symptomatic Visceral Leishmaniasis
      Cases: Findings from Situation Assessment in High Endemic Foci in India.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is highly prevalent in the Indian state
      of Bihar and, without proper diagnosis and treatment, is associated with high
      fatality. However, lack of efficient reporting mechanism had been an impediment
      in estimating the burden of mortality and its antecedents among symptomatic VL
      cases. The objectives of the current study were to generate a reliable estimate
      of symptomatic VL caseload and mortality in Bihar, as well as to identify the
      epidemiologic and health infrastructure-related predictors of VL mortality.
      METHODOLOGY AND PRINCIPAL FINDINGS: Using an elaborate index case tracing method,
      we attempted to locate all symptomatic VL patients in eight districts of Bihar.
      Interviews and medical-record-reviews were conducted with cases (or next-of-kin
      for the dead) meeting the eligibility criteria. The information collected during
      the interviews included socio-demographic characteristics, onset of disease
      symptoms, place of diagnosis, pre- and post-diagnosis treatment history, type and
      duration of drugs received. In total, we analyzed data on 4925 VL patients-59%
      were male and 68% were less than 30 years old. There were 158 (3.2%) deaths and
      the incidence rate of mortality was 3.2/100 person-years. In the adjusted Cox
      proportional-hazards analysis, treatment at public facility [Adjusted Hazard
      Ratio (AHR) = 0.61; 95% CI = 0.43-0.86], shorter (<=30 days) diagnostic delay
      [AHR = 0.62, 95% CI = 0.43-0.92], and treatment completion [AHR = 0.03, 95% CI =
      0.02-0.05] emerged as significant negative predictors of mortality. CONCLUSION:
      Mortality reduction efforts in Bihar should focus on improving access to early
      diagnosis, quality treatment and treatment-adherence measures, with special
      emphasis on marginalized communities.

PMID- 27870871
TI  - Functional Genomic Analysis of Candida albicans Adherence Reveals a Key Role for
      the Arp2/3 Complex in Cell Wall Remodelling and Biofilm Formation.
AB  - Fungal biofilms are complex, structured communities that can form on surfaces
      such as catheters and other indwelling medical devices. Biofilms are of
      particular concern with Candida albicans, one of the leading opportunistic fungal
      pathogens of humans. C. albicans biofilms include yeast and filamentous cells
      that are surrounded by an extracellular matrix, and they are intrinsically
      resistant to antifungal drugs such that resolving biofilm infections often
      requires surgery to remove the contaminated device. C. albicans biofilms form
      through a regulated process of adhesion to surfaces, filamentation, maturation,
      and ultimately dispersion. To uncover new strategies to block the initial stages
      of biofilm formation, we utilized a functional genomic approach to identify genes
      that modulate C. albicans adherence. We screened a library of 1,481 double
      barcoded doxycycline-repressible conditional gene expression strains covering
      ~25% of the C. albicans genome. We identified five genes for which
      transcriptional repression impaired adherence, including: ARC18, PMT1, MNN9,
      SPT7, and orf19.831. The most severe adherence defect was observed upon
      transcriptional repression of ARC18, which encodes a member of the Arp2/3 complex
      that is involved in regulation of the actin cytoskeleton and endocytosis.
      Depletion of components of the Arp2/3 complex not only impaired adherence, but
      also caused reduced biofilm formation, increased cell surface hydrophobicity, and
      increased exposure of cell wall chitin and beta-glucans. Reduced function of the
      Arp2/3 complex led to impaired cell wall integrity and activation of Rho1
      mediated cell wall stress responses, thereby causing cell wall remodelling and
      reduced adherence. Thus, we identify important functional relationships between
      cell wall stress responses and a novel mechanism that controls adherence and
      biofilm formation, thereby illuminating novel strategies to cripple a leading
      fungal pathogen of humans.

PMID- 27870872
TI  - Aberrant IgA1 Glycosylation in IgA Nephropathy: A Systematic Review.
AB  - OBJECTIVE: Galactose-deficient IgA1 was evaluated in patients with IgA
      nephropathy(IgAN) and controls in order to determine the predictive value of
      galactose-deficient IgA1 in cases of IgA nephropathy. METHODS: PubMed, EMBASE,
      Cochrane central register of controlled trials, CNKI, CBM disc, and VIP database
      were searched to identify eligible studies that evaluated a difference in
      aberrant IgA1 glycosylation in IgAN patients compared with controls. A meta
      analysis was conducted to evaluate the impact of galactose-deficient IgA1(Gd
      IgA1) levels in different groups. RESULTS: A total of 22 studies (n = 1657) met
      inclusion criteria. The mean Newcastle-Ottawa Scale (NOS) score was 7.2 and
      ranged from 6 to 8. The standard mean difference(SMD) in the meta-analysis of 20
      studies of the level of Gd-IgA1 in the serum and/or supernatant of cultured cells
      was higher in the IgAN group compared with healthy controls as well as in those
      with other renal diseases (SMD = 1.76, 95% CI = 1.18-2.34, P<0.00001; SMD = 1.05,
      95% CI = 0.05-2.04, P = 0.04). The data synthesis suggested that IgAN patients
      had similar levels of serum Gd-IgA1, with no significant differences, compared
      with first-degree relatives and Henoch-Schonlein purpura nephritis (HSPN)
      patients (MD = 0.04, 95% CI = 0.00-0.08, P = 0.05; MD = -46.03, 95% CI = -217.70
      125.64, P = 0.60). In addition, the combined MD of 5 studies indicated that there
      were no significant differences in Gd-IgA1 levels among patients with varying
      severities of IgAN (MD = 0.02, 95% CI = -0.02-0.05, P = 0.28). CONCLUSIONS: The
      pooled evidence suggests that the level of Gd-IgA1 in the serum or supernatant of
      cultured cells from peripheral blood or tonsils may be a useful biomarker for
      predicting IgA nephropathy, though the level of Gd-IgA1 was not significantly
      associated with disease severity.

PMID- 27870873
TI  - Herbivore-Induced DNA Demethylation Changes Floral Signalling and Attractiveness
      to Pollinators in Brassica rapa.
AB  - Plants have to fine-tune their signals to optimise the trade-off between
      herbivore deterrence and pollinator attraction. An important mechanism in
      mediating plant-insect interactions is the regulation of gene expression via DNA
      methylation. However, the effect of herbivore-induced DNA methylation changes on
      pollinator-relevant plant signalling has not been systematically investigated.
      Here, we assessed the impact of foliar herbivory on DNA methylation and floral
      traits in the model crop plant Brassica rapa. Methylation-sensitive amplified
      fragment length polymorphism (MSAP) analysis showed that leaf damage by the
      caterpillar Pieris brassicae was associated with genome-wide methylation changes
      in both leaves and flowers of B. rapa as well as a downturn in flower number,
      morphology and scent. A comparison to plants with jasmonic acid-induced defence
      showed similar demethylation patterns in leaves, but both the floral methylome
      and phenotype differed significantly from P. brassicae infested plants.
      Standardised genome-wide demethylation with 5-azacytidine in five different B.
      rapa full-sib groups further resulted in a genotype-specific downturn of floral
      morphology and scent, which significantly reduced the attractiveness of the
      plants to the pollinator bee Bombus terrestris. These results suggest that DNA
      methylation plays an important role in adjusting plant signalling in response to
      changing insect communities.

PMID- 27870874
TI  - Associations between Season and Gametocyte Dynamics in Chronic Plasmodium
      falciparum Infections.
AB  - INTRODUCTION: In a markedly seasonal malaria setting, the transition from the
      transmission-free dry season to the transmission season depends on the resurgence
      of the mosquito population following the start of annual rains. The sudden onset
      of malaria outbreaks at the start of the transmission season suggests that
      parasites persist during the dry season and respond to either the reappearance of
      vectors, or correlated events, by increasing the production of transmission
      stages. Here, we investigate whether Plasmodium falciparum gametocyte density and
      the correlation between gametocyte density and parasite density show seasonal
      variation in chronic (largely asymptomatic) carriers in eastern Sudan. MATERIALS
      AND METHODS: We recruited and treated 123 malaria patients in the transmission
      season 2001. We then followed them monthly during four distinct consecutive
      epidemiological seasons: transmission season 1, transmission-free season, pre
      clinical period, and transmission season 2. In samples collected from 25
      participants who fulfilled the selection criteria of the current analysis, we
      used quantitative PCR (qPCR) and RT-qPCR to quantify parasite and gametocyte
      densities, respectively. RESULTS AND DISCUSSION: We observed a significant
      increase in gametocyte density and a significantly steeper positive correlation
      between gametocyte density and total parasite density during the pre-clinical
      period compared to the preceding transmission-free season. However, there was no
      corresponding increase in the density or prevalence of total parasites or
      gametocyte prevalence. The increase in gametocyte production during the pre
      clinical period supports the hypothesis that P. falciparum may respond to
      environmental cues, such as mosquito biting, to modulate its transmission
      strategy. Thus, seasonal changes may be important to ignite transmission in
      unstable-malaria settings.

PMID- 27870875
TI  - A Novel Organ Culture Model to Quantify Collagen Remodeling in Tree Shrew Sclera.
AB  - Increasing evidence suggests that unknown collagen remodeling mechanisms in the
      sclera underlie myopia development. We are proposing a novel organ culture system
      in combination with two-photon fluorescence imaging to quantify collagen
      remodeling at the tissue- and lamella-level. Tree shrew scleral shells were
      cultured up to 7 days in serum-free media and cellular viability was investigated
      under: (i) minimal tissue manipulations; (ii) removal of intraocular tissues;
      gluing the eye to a washer using (iii) 50 MUL and (iv) 200 MUL of cyanoacrylate
      adhesive; (v) supplementing media with Ham's F-12 Nutrient Mixture; and (vi)
      culturing eyes subjected to 15 mmHg intraocular pressure in our new bioreactor.
      Two scleral shells of normal juvenile tree shrews were fluorescently labeled
      using a collagen specific protein and cultured in our bioreactor. Using two
      photon microscopy, grid patterns were photobleached into and across multiple
      scleral lamellae. These patterns were imaged daily for 3 days, and tissue
      /lamella-level strains were calculated from the deformed patterns. No significant
      reduction in cell viability was observed under conditions (i) and (v). Compared
      to condition (i), cell viability was significantly reduced starting at day 0
      (condition (ii)) and day 3 (conditions (iii, iv, vi)). Tissue-level strain and
      intralamellar shear angel increased significantly during the culture period. Some
      scleral lamellae elongated while others shortened. Findings suggest that tree
      shrew sclera can be cultured in serum-free media for 7 days with no significant
      reduction in cell viability. Scleral fibroblasts are sensitive to tissue
      manipulations and tissue gluing. However, Ham's F-12 Nutrient Mixture has a
      protective effect on cell viability and can offset the cytotoxic effect of
      cyanoacrylate adhesive. This is the first study to quantify collagen micro
      deformations over a prolonged period in organ culture providing a new methodology
      to study scleral remodeling in myopia.

PMID- 27870876
TI  - Reduced PICD in Monocytes Mounts Altered Neonate Immune Response to Candida
      albicans.
AB  - BACKGROUND: Invasive fungal infections with Candida albicans (C. albicans) occur
      frequently in extremely low birthweight (ELBW) infants and are associated with
      poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes
      (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood
      monocytes (CBMO). HYPOTHESIS: Phagocytosis of C. albicans causes PICD which
      differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes
      (PBMO) due to lower stimulation of TLR-mediated immune responses. METHODS: The
      ability to phagocytose C. albicans, expression of TLRs, the induction of
      apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS.
      TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys,
      FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor).
      RESULTS: Phagocytic indices of PBMO and CBMO were similar. Following stimulation
      with agonists and C. albicans induced up-regulation of TLR2 and consecutive
      phosphorylation of MAP kinase P38 and expression of TNF-alpha, which were
      stronger on PBMO compared to CBMO (p < 0.005). Downstream, TLR2 signalling
      initiated caspase-3-dependent PICD which was found reduced in CBMO (p < 0.05 vs
      PBMO). CONCLUSION: Our data suggest direct involvement of TLR2-signalling in C.
      albicans-induced PICD in monocytes and an alteration of this pathway in CBMO.

PMID- 27870877
TI  - Nut Cracking Tools Used by Captive Chimpanzees (Pan troglodytes) and Their
      Comparison with Early Stone Age Percussive Artefacts from Olduvai Gorge.
AB  - We present the results of a series of experiments at the Kumamoto Sanctuary in
      Japan, in which captive chimpanzees (Pan troglodytes) performed several nut
      cracking sessions using raw materials from Olduvai Gorge, Tanzania. We examined
      captive chimpanzee pounding tools using a combination of technological analysis,
      use-wear distribution, and micro-wear analysis. Our results show specific
      patterns of use-wear distribution across the active surfaces of pounding tools,
      which reveal some similarities with traces on archaeological percussive objects
      from the Early Stone Age, and are consistent with traces on other experimental
      pounding tools used by modern humans. The approach used in this study may help to
      stablish a framework with which to interpret archaeological assemblages and
      improve understanding of use-wear formation processes on pounding tools used by
      chimpanzees. This study represents the first direct comparison of chimpanzee
      pounding tools and archaeological material, and thus may contribute to a better
      understanding of hominin percussive activities.

PMID- 27870878
TI  - 3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental
      Feedback from Film Dosimetry.
AB  - A model based on a specific phantom, called QuAArC, has been designed for the
      evaluation of planning and verification systems of complex radiotherapy
      treatments, such as volumetric modulated arc therapy (VMAT). This model uses the
      high accuracy provided by the Monte Carlo (MC) simulation of log files and allows
      the experimental feedback from the high spatial resolution of films hosted in
      QuAArC. This cylindrical phantom was specifically designed to host films rolled
      at different radial distances able to take into account the entrance fluence and
      the 3D dose distribution. Ionization chamber measurements are also included in
      the feedback process for absolute dose considerations. In this way, automated MC
      simulation of treatment log files is implemented to calculate the actual delivery
      geometries, while the monitor units are experimentally adjusted to reconstruct
      the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck
      clinical cases, previously planned with Monaco and Pinnacle treatment planning
      systems and verified with two different commercial systems (Delta4 and COMPASS),
      were selected in order to test operational feasibility of the proposed model. The
      proper operation of the feedback procedure was proved through the achieved high
      agreement between reconstructed dose distributions and the film measurements
      (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary
      discretization level of the log file for dose calculation and the potential
      mismatching between calculated control points and detection grid in the
      verification process were discussed. Besides the effect of dose calculation
      accuracy of the analytic algorithm implemented in treatment planning systems for
      a dynamic technique, it was discussed the importance of the detection density
      level and its location in VMAT specific phantom to obtain a more reliable DVH in
      the patient CT. The proposed model also showed enough robustness and efficiency
      to be considered as a pre-treatment VMAT verification system.

PMID- 27870880
TI  - How Simple Hypothetical-Choice Experiments Can Be Utilized to Learn Humans'
      Navigational Escape Decisions in Emergencies.
AB  - How humans resolve non-trivial tradeoffs in their navigational choices between
      the social interactions (e.g., the presence and movements of others) and the
      physical factors (e.g., spatial distances, route visibility) when escaping from
      threats in crowded confined spaces? The answer to this question has major
      implications for the planning of evacuations and the safety of mass gatherings as
      well as the design of built environments. Due to the challenges of collecting
      behavioral data from naturally-occurring evacuation settings, laboratory-based
      virtual-evacuation experiments have been practiced in a number of studies. This
      class of experiments faces the traditional question of contextual bias and
      generalizability: How reliably can we infer humans' behavior from decisions made
      in hypothetical settings? Here, we address these questions by making a novel link
      between two different forms of empirical observations. We conduct hypothetical
      emergency exit-choice experiments framed as simple pictures, and then mimic those
      hypothetical scenarios in more realistic fashions through staging mock evacuation
      trials with actual crowds. Econometric choice models are estimated based on the
      observations made in both experimental contexts. The models are contrasted with
      each other from a number of perspectives including their predictions as well as
      the sign, magnitude, statistical significance, person-to-person variations
      (reflecting individuals' perception/preference differences) and the scale
      (reflecting context-dependent decision randomness) of their inferred parameters.
      Results reveal a surprising degree of resemblance between the models derived from
      the two contexts. Most strikingly, they produce fairly similar prediction
      probabilities whose differences average less than 10%. There is also unexpected
      consensus between the inferences derived from both experimental sources on many
      aspects of people's behavior notably in terms of the perception of social
      interactions. Results show that we could have elicited peoples' escape strategies
      with fair precision without observing them in action (i.e., simply by using only
      hypothetical-choice data as an inexpensive, practical and non-invasive
      experimental technique in this context). As a broader application, this offers
      promising evidence as to the potential applicability of the hypothetical-decision
      experiments to other decision contexts (at least for non-financial decisions)
      when field or real-world data is prohibitively unavailable. As a practical
      application, the behavioral insights inferred from our observations (reflected in
      the estimated parameters) can improve how accurately we predict the movement
      patterns of human crowds in emergency scenarios arisen in complex spaces. Fully
      generic-in-parameters, our proposed models can even be directly introduced to a
      broad range of crowd simulation software to replicate navigation decision making
      of evacuees.

PMID- 27870879
TI  - Occurrence of Diverse Antimicrobial Resistance Determinants in Genetically
      Unrelated Biocide Tolerant Klebsiella pneumoniae.
AB  - Nosocomial infections due to Klebsiella pneumoniae is a significant problem in
      health care settings worldwide. In this study, we examined the antimicrobial
      susceptibility, genetic profiles and mechanisms of antibiotic resistance in K.
      pneumoniae isolates of Indian origin. To our knowledge this is the first report
      demonstrating the high prevalence of beta-lactamases, aminoglycoside modifying
      enzymes, quinolone resistance genes besides demonstrating the involvement of
      active efflux in K. pneumoniae Indian isolates. This study has enabled us to
      correlate the phenotypic and genotypic characteristics in K. pneumoniae,
      providing an important base for continued monitoring and epidemiological studies
      of this emerging nosocomial pathogen in Indian hospitals.

PMID- 27870881
TI  - Associations between XRCC1 Gene Polymorphisms and Coronary Artery Disease: A Meta
      Analysis.
AB  - Genetic variations that influence DNA repair efficiency may contribute to
      coronary artery disease (CAD) susceptibility. Previous studies have investigated
      whether there was evidence of an association between polymorphisms at the X-ray
      repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings
      have been inconclusive. We identified eligible studies through a comprehensive
      literature search to determine whether an association exists between XRCC1 gene
      polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio
      (OR) and corresponding 95% confidence interval (CI), which were calculated using
      a fixed- or random-effects model, based on the heterogeneity of the studies. Ten
      eligible studies were finally included in this meta-analysis. Our pooled analysis
      found that XRCC1 polymorphisms were significantly associated with CAD
      susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13-1.93;
      Arg399Gln: OR = 1.45, 95% CI = 1.12-1.89), homozygous (Arg194Trp: OR = 1.37, 95%
      CI = 1.03-1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19-2.05), and allele (Arg399Gln:
      OR = 1.18, 95% CI = 1.06-1.32) genetic models. Following subgroup analysis by
      ethnicity, in Asian populations, we found evidence of associations between the
      XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic
      models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive,
      homozygous, and allele genetic models. Subgroup analysis stratified by control
      source revealed associations between the Arg194Trp and Arg399Gln polymorphisms
      and susceptibility to CAD under recessive and homozygous modes of inheritance,
      respectively. In addition, subgroup analysis stratified by sample size found that
      findings of the Arg194Trp polymorphism in large sample sizes were comparable to
      those found using pooled eligible studies. Based on our meta-analysis, we
      concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are
      associated with CAD susceptibility, specifically in Asian populations. However,
      additional, comprehensive and well-designed studies are warranted to confirm
      these findings.

PMID- 27870882
TI  - Immune Activation at Sites of HIV/TB Co-Infection Contributes to the Pathogenesis
      of HIV-1 Disease.
AB  - Systemic immune activation is critical to the pathogenesis of HIV-1 disease, and
      is accentuated in HIV/TB co-infected patients. The contribution of immune
      activation at sites of HIV/TB co-infection to viral activity, CD4 T cell count,
      and productive HIV-1 infection remain unclear. In this study, we measured markers
      of immune activation both in pleural fluid and plasma, and in T cells in pleural
      fluid mononuclear cell (PFMC) and peripheral blood mononuclear cell (PBMC) in
      HIV/TB co-infected subjects. The relationship between soluble and T cell
      activation markers with viral load in pleural fluid and blood CD4 T cell count
      were assessed. The T cell phenotype and activation status of HIV-1 p24 + T cells
      in PFMC and PBMC from HIV/TB patients were determined. We found that T cell and
      macrophage-specific and non-specific soluble markers of immune activation, sCD27,
      sCD163, IL1Ra, and sCD14, were higher in pleural fluid as compared to plasma from
      HIV/TB co-infected subjects, and higher as compared to pleural fluid from TB mono
      infected subjects. Intestinal fatty acid-binding protein, a marker of intestinal
      tract damage, in plasma from HIV/TB co-infected patients was not different than
      that in HIV+ subjects. Expression of HLADR and CD38 double positive (HLADR/CD38)
      on CD4 T cells, and CD69+ on CD8 T cells correlated with pleural fluid viral
      load, and inversely with blood CD4 T cell count. Higher expression of HLADR/CD38
      and CCR5 on CD4 T cells, and HLADR/CD38 and CD69 on CD8 T cells in PFMC were
      limited to effector memory populations. HIV-1 p24+ CD8 negative (includes CD4 +
      and double negative T cells) effector memory T cells in PFMC had higher
      expression of HLADR/CD38, Ki67, and CCR5 compared to HIV-1 p24- CD8 negative
      PFMC. Cumulatively, these data indicate that sites of HIV/TB co-infection are the
      source of intense immune activation.

PMID- 27870883
TI  - Association between Leptin and Complement in Hepatitis C Patients with Viral
      Clearance: Homeostasis of Metabolism and Immunity.
AB  - BACKGROUND: The association between leptin and complement in hepatitis C virus
      (HCV) infection remains unknown. METHODS: A prospective study was conducted
      including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C
      (CHC) patients who had completed an anti-HCV therapy course and undergone pre
      therapy and 24-week post-therapy assessments of interferon lambda3-rs12979860 and
      HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and
      complement component 3 (C3), C4, and leptin levels. RESULTS: Of the 474 patients,
      395 had a sustained virological response (SVR). Pre-therapy leptin levels did not
      differ between patients with and without an SVR. Univariate and multivariate
      analyses showed that sex (pre- and post-therapy, p<0.001), body mass index (BMI)
      (pre- and post-therapy, p<0.001), and C3 levels (pre-therapy, p = 0.027; post
      therapy, p = 0.02) were independently associated with leptin levels with or
      without HCV infection. Pre-therapy BMI, total cholesterol (TC), C4 levels, and
      the rs12979860 genotype were independently associated with pre-therapy C3 levels
      in all patients. Post-therapy BMI, alanine aminotransferase, TC, C4 levels, white
      blood cell counts, and hepatic steatosis were independently associated with the
      post-therapy C3 levels of SVR patients. Compared with pre-therapy levels, SVR
      patients showed higher 24-week post-therapy C4 (20.32+/-7.30 vs. 21.55+/-7.07
      mg/dL, p<0.001) and TC (171.68+/-32.67 vs. 186.97+/-36.09 mg/dL, p<0.001) levels;
      however, leptin and C3 levels remained unchanged after therapy in patients with
      and without an SVR. CONCLUSIONS: Leptin and C3 may maintain immune and metabolic
      homeostasis through association with C4 and TC. Positive alterations in C4 and TC
      levels reflect viral clearance after therapy in CHC patients.

PMID- 27870884
TI  - Non-Specific Root Transport of Nutrient Gives Access to an Early Nutritional
      Indicator: The Case of Sulfate and Molybdate.
AB  - Under sulfur (S) deficiency, crosstalk between nutrients induced accumulation of
      other nutrients, particularly molybdenum (Mo). This disturbed balanced between S
      and Mo could provide a way to detect S deficiency and therefore avoid losses in
      yield and seed quality in cultivated species. Under hydroponic conditions, S
      deprivation was applied to Brassica napus to determine the precise kinetics of S
      and Mo uptake and whether sulfate transporters were involved in Mo uptake. Leaf
      contents of S and Mo were also quantified in a field-grown S deficient oilseed
      rape crop with different S and N fertilization applications to evaluate the
      [Mo]:[S] ratio, as an indicator of S nutrition. To test genericity of this
      indicator, the [Mo]:[S] ratio was also assessed with other cultivated species
      under different controlled conditions. During S deprivation, Mo uptake was
      strongly increased in B. napus. This accumulation was not a result of the
      induction of the molybdate transporters, Mot1 and Asy, but could be a direct
      consequence of Sultr1.1 and Sultr1.2 inductions. However, analysis of single
      mutants of these transporters in Arabidopsis thaliana suggested that other
      sulfate deficiency responsive transporters may be involved. Under field
      conditions, Mo content was also increased in leaves by a reduction in S
      fertilization. The [Mo]:[S] ratio significantly discriminated between the plots
      with different rates of S fertilization. Threshold values were estimated for the
      hierarchical clustering of commercial crops according to S status. The use of the
      [Mo]:[S] ratio was also reliable to detect S deficiency for other cultivated
      species under controlled conditions. The analysis of the leaf [Mo]:[S] ratio
      seems to be a practical indicator to detect early S deficiency under field
      conditions and thus improve S fertilization management.

PMID- 27870885
TI  - A Negative Relationship between Foliar Carbon Isotope Composition and Mass-Based
      Nitrogen Concentration on the Eastern Slope of Mount Gongga, China.
AB  - Plants adopt ecological strategy to resist environmental changes and increase
      their resource-use efficiency. The ecological strategy includes changes in
      physiological traits and leaf morphology, which may result in simultaneous
      variations in foliar N concentration and the ratio of intercellular CO2
      concentration to ambient CO2 concentration (ci/ca). This in turn links to foliar
      carbon isotope discrimination, and thus, a relationship between foliar N
      concentration and foliar carbon isotope composition (delta13C) is expected. To
      understand how plants integrate their structural and physiological resistance to
      environmental changes, the relationship between foliar N concentration and
      foliardelta13C has been assessed intensively, especially the correlation between
      area-based N concentration (Narea) and delta13C.Less effort has been dedicated to
      the examination of the relationship between mass-based N concentration(Nmass) and
      delta13C. Studies on the Nmass-delta13C relationship, especially those including
      a large amount of data and species, will enhance our understanding of leaf
      economics and benefit ecological modeling. The present study includes an
      intensive investigation into this relationship by measuring foliar Nmass and
      delta13C in a large number of plant species grown on the eastern slope of Mount
      Gongga, China. This study shows that foliar Nmass decreases with increasing
      delta13C, which is independent of functional group, vegetation type, and
      altitude. This suggests that a negative correlation between Nmass and delta13C
      may be a general pattern for plants grown not only on Mount Gongga, but also in
      other areas.

PMID- 27870886
TI  - Comparative Genomics Revealed Multiple Helicobacter pylori Genes Associated with
      Biofilm Formation In Vitro.
AB  - BACKGROUND: Biofilm formation by Helicobacter pylori may be one of the factors
      influencing eradication outcome. However, genetic differences between good and
      poor biofilm forming strains have not been studied. MATERIALS AND METHODS:
      Biofilm yield of 32 Helicobacter pylori strains (standard strain and 31 clinical
      strains) were determined by crystal-violet assay and grouped into poor, moderate
      and good biofilm forming groups. Whole genome sequencing of these 32 clinical
      strains was performed on the Illumina MiSeq platform. Annotation and comparison
      of the differences between the genomic sequences were carried out using RAST
      (Rapid Annotation using Subsystem Technology) and SEED viewer. Genes identified
      were confirmed using PCR. RESULTS: Genes identified to be associated with biofilm
      formation in H. pylori includes alpha (1,3)-fucosyltransferase, flagellar
      protein, 3 hypothetical proteins, outer membrane protein and a cag pathogenicity
      island protein. These genes play a role in bacterial motility, lipopolysaccharide
      (LPS) synthesis, Lewis antigen synthesis, adhesion and/or the type-IV secretion
      system (T4SS). Deletion of cagA and cagPAI confirmed that CagA and T4SS were
      involved in H. pylori biofilm formation. CONCLUSIONS: Results from this study
      suggest that biofilm formation in H. pylori might be genetically determined and
      might be influenced by multiple genes. Good, moderate and poor biofilm forming
      strain might differ during the initiation of biofilm formation.

PMID- 27870887
TI  - Epidermal Growth Factor Receptor and Ki-67 as Predictive Biomarkers Identify
      Patients Who Will Be More Sensitive to Intravesical Instillations for the
      Prevention of Bladder Cancer Recurrence after Radical Nephroureterectomy.
AB  - BACKGROUND: To date, prophylactic intravesical chemotherapy after radical
      nephroureterectomy is one of the few available treatments that effectively
      prevent secondary bladder cancer. However, treating all patients with
      prophylactic intravesical chemotherapy is excessive for patients who are at a low
      risk or insensitive to the treatment. Thus, to guide individualized clinical
      treatment, in addition to identifying patients who are at risk of bladder cancer
      recurrence, it is equally necessary to identify the patients who will benefit the
      most from prophylactic, postoperative intravesical instillation therapy. METHODS:
      Epidermal growth factor receptor (EGFR) and Ki-67 expression levels were measured
      using immunohistochemical staining samples from 320 patients with upper urinary
      tract urothelial carcinoma (UTUC) from 2004 to 2012. Although no patients
      received intravesical chemotherapy after RNU before 2008, this method began to be
      used in 2008 to prevent bladder cancer recurrence. To identify the patients who
      would most benefit from intravesical chemotherapy, we assessed biological
      interactions between intravesical chemotherapy and clinicopathological factors or
      biomarkers. RESULTS: The incidence rates of bladder UTUC recurrence decreased
      after intravesical chemotherapy, and the decrease was greater in patients with
      low Ki-67 levels, negative EGFR staining and preoperative positive urine
      cytology. Biological interactions were observed between intravesical
      chemotherapy, low-level Ki-67 and EGFR negativity. The multivariate analysis
      showed that after balancing a variety of factors, intravesical chemotherapy is a
      protective factor for preventing intravesical recurrence in the negative EGFR,
      low-level Ki-67 and preoperative positive urine cytology sub-groups but not in
      their corresponding sub-groups. Additionally, the multivariate analysis revealed
      that preoperative positive urine cytology and Ki-67 were not but that EGFR
      positivity was an independent risk factor for recurrence after intravesical
      chemotherapy. CONCLUSIONS: Patients with low Ki-67 levels, negative EGFR staining
      and preoperative positive urine cytology appear to be more sensitive to
      intravesical instillations for bladder recurrence prevention after RNU.

PMID- 27870888
TI  - Phylogeographic Insights into a Peripheral Refugium: The Importance of Cumulative
      Effect of Glaciation on the Genetic Structure of Two Endemic Plants.
AB  - Quaternary glaciations and mostly last glacial maximum have shaped the
      contemporary distribution of many species in the Alps. However, in the Maritime
      and Ligurian Alps a more complex picture is suggested by the presence of many
      Tertiary paleoendemisms and by the divergence time between lineages in one
      endemic species predating the Late Pleistocene glaciation. The low number of
      endemic species studied limits the understanding of the processes that took place
      within this region. We used species distribution models and phylogeographical
      methods to infer glacial refugia and to reconstruct the phylogeographical pattern
      of Silene cordifolia All. and Viola argenteria Moraldo & Forneris. The predicted
      suitable area for last glacial maximum roughly fitted current known distribution.
      Our results suggest that separation of the major clades predates the last glacial
      maximum and the following repeated glacial and interglacial periods probably
      drove differentiations. The complex phylogeographical pattern observed in the
      study species suggests that both populations and genotypes extinction was minimal
      during the last glacial maximum, probably due to the low impact of glaciations
      and to topographic complexity in this area. This study underlines the importance
      of cumulative effect of previous glacial cycles in shaping the genetic structure
      of plant species in Maritime and Ligurian Alps, as expected for a Mediterranean
      mountain region more than for an Alpine region.

PMID- 27870889
TI  - How Effective Is Road Mitigation at Reducing Road-Kill? A Meta-Analysis.
AB  - Road traffic kills hundreds of millions of animals every year, posing a critical
      threat to the populations of many species. To address this problem there are more
      than forty types of road mitigation measures available that aim to reduce
      wildlife mortality on roads (road-kill). For road planners, deciding on what
      mitigation method to use has been problematic because there is little good
      information about the relative effectiveness of these measures in reducing road
      kill, and the costs of these measures vary greatly. We conducted a meta-analysis
      using data from 50 studies that quantified the relationship between road-kill and
      a mitigation measure designed to reduce road-kill. Overall, mitigation measures
      reduce road-kill by 40% compared to controls. Fences, with or without crossing
      structures, reduce road-kill by 54%. We found no detectable effect on road-kill
      of crossing structures without fencing. We found that comparatively expensive
      mitigation measures reduce large mammal road-kill much more than inexpensive
      measures. For example, the combination of fencing and crossing structures led to
      an 83% reduction in road-kill of large mammals, compared to a 57% reduction for
      animal detection systems, and only a 1% for wildlife reflectors. We suggest that
      inexpensive measures such as reflectors should not be used until and unless their
      effectiveness is tested using a high-quality experimental approach. Our meta
      analysis also highlights the fact that there are insufficient data to answer many
      of the most pressing questions that road planners ask about the effectiveness of
      road mitigation measures, such as whether other less common mitigation measures
      (e.g., measures to reduce traffic volume and/or speed) reduce road mortality, or
      to what extent the attributes of crossing structures and fences influence their
      effectiveness. To improve evaluations of mitigation effectiveness, studies should
      incorporate data collection before the mitigation is applied, and we recommend a
      minimum study duration of four years for Before-After, and a minimum of either
      four years or four sites for Before-After-Control-Impact designs.

PMID- 27870890
TI  - Latitudinal Diversity of Culex pipiens Biotypes and Hybrids in Farm, Peri-Urban,
      and Wetland Habitats in Europe.
AB  - Despite the presence of Culex (Cx.) pipiens mosquitoes and circulation of West
      Nile virus (WNV), WNV outbreaks have so far not occurred in northern Europe. The
      species Cx. pipiens consists of two morphologically identical biotypes, pipiens
      and molestus, which can form hybrids. Until now, population dynamic studies of
      Cx. pipiens have not differentiated between biotypes and hybrids at the European
      scale, nor have they used comparative surveillance approaches. We therefore aimed
      to elucidate the relative abundance of Cx. pipiens biotypes and hybrids in three
      habitat types at different latitudes across Europe, using two different
      surveillance traps. BG-Sentinel and Mosquito-Magnet Liberty Plus traps were
      placed in three habitat types (farms, peri-urban, wetlands), in three European
      countries (Sweden, The Netherlands, Italy). Collected Cx. pipiens mosquitoes were
      identified to biotype with real-time PCR. Both trap types collected equal ratios
      of the biotypes and their hybrids. From northern to southern latitudes there was
      a significant decrease of pipiens and an increase of molestus. Habitat types
      influenced the relative ratios of biotypes and hybrids, but results were not
      consistent across latitudes. Our results emphasize the need to differentiate Cx.
      pipiens to the biotype level, especially for proper future WNV risk assessments
      for Europe.

PMID- 27870892
TI  - Body Weight Can Change How Your Emotions Are Perceived.
AB  - Accurately interpreting other's emotions through facial expressions has important
      adaptive values for social interactions. However, due to the stereotypical social
      perception of overweight individuals as carefree, humorous, and light-hearted,
      the body weight of those with whom we interact may have a systematic influence on
      our emotion judgment even though it has no relevance to the expressed emotion
      itself. In this experimental study, we examined the role of body weight in faces
      on the affective perception of facial expressions. We hypothesized that the
      weight perceived in a face would bias the assessment of an emotional expression,
      with overweight faces generally more likely to be perceived as having more
      positive and less negative expressions than healthy weight faces. Using two
      alternative forced-choice perceptual decision tasks, participants were asked to
      sort the emotional expressions of overweight and healthy weight facial stimuli
      that had been gradually morphed across six emotional intensity levels into one of
      two categories-"neutral vs. happy" (Experiment 1) and "neutral vs. sad"
      (Experiment 2). As predicted, our results demonstrated that overweight faces were
      more likely to be categorized as happy (i.e., lower happy decision threshold) and
      less likely to be categorized as sad (i.e., higher sad decision threshold)
      compared to healthy weight faces that had the same levels of emotional intensity.
      The neutral-sad decision threshold shift was negatively correlated with
      participant's own fear of becoming fat, that is, those without a fear of becoming
      fat more strongly perceived overweight faces as sad relative to those with a
      higher fear. These findings demonstrate that the weight of the face
      systematically influences how its emotional expression is interpreted, suggesting
      that being overweight may make emotional expressions appear more happy and less
      sad than they really are.

PMID- 27870891
TI  - oxLDL and eLDL Induced Membrane Microdomains in Human Macrophages.
AB  - BACKGROUND: Extravasation of macrophages and formation of lipid-laden foam cells
      are key events in the development and progression of atherosclerosis. The
      degradation of atherogenic lipoproteins subsequently leads to alterations in
      cellular lipid metabolism that influence inflammatory signaling. Especially
      sphingolipids and ceramides are known to be involved in these processes. We
      therefore analyzed monocyte derived macrophages during differentiation and after
      loading with enzymatically (eLDL) and oxidatively (oxLDL) modified low-density
      lipoproteins (LDL). METHODS: Primary human monocytes were isolated from healthy,
      normolipidemic blood donors using leukapheresis and counterflow elutriation. On
      the fourth day of MCSF-induced differentiation eLDL (40 MUg/ml) or oxLDL (80
      MUg/ml) were added for 48h. Lipid species were analyzed by quantitative tandem
      mass spectrometry. Taqman qPCR was performed to investigate transcriptional
      changes in enzymes involved in sphingolipid metabolism. Furthermore, membrane
      lipids were studied using flow cytometry and confocal microscopy. RESULTS: MCSF
      dependent phagocytic differentiation of blood monocytes had only minor effects on
      the sphingolipid composition. Levels of total sphingomyelin and total ceramide
      remained unchanged, while lactosylceramides, cholesterylesters and free
      cholesterol decreased. At the species level most ceramide species showed a
      reduction upon phagocytic differentiation. Loading with eLDL preferentially
      increased cellular cholesterol while loading with oxLDL increased cellular
      ceramide content. Activation of the salvage pathway with a higher mRNA expression
      of acid and neutral sphingomyelinase, neutral sphingomyelinase activation
      associated factor and glucosylceramidase as well as increased surface expression
      of SMPD1 were identified as potentially underlying mechanisms. Moreover, flow
      cytometric analysis revealed a higher cell-surface-expression of ceramide,
      lactosylceramide (CDw17), globotriaosylceramide (CD77), dodecasaccharide-ceramide
      (CD65s) and GM1 ganglioside upon oxLDL loading. ApoE in contrast to apoA-I
      preferentially bound to the ceramide enriched surfaces of oxLDL loaded cells.
      Confocal microscopy showed a co-localization of acid sphingomyelinase with
      ceramide rich membrane microdomains. CONCLUSION: eLDL leads to the formation of
      lipid droplets and preferentially induces cholesterol/sphingomyelin rich membrane
      microdomains while oxLDL promotes the development of cholesterol/ceramide rich
      microdomains via activation of the salvage pathway.

PMID- 27870893
TI  - Activin Receptor Type IIB Inhibition Improves Muscle Phenotype and Function in a
      Mouse Model of Spinal Muscular Atrophy.
AB  - Spinal muscular atrophy (SMA) is a devastating neurodegenerative disorder that
      causes progressive muscle atrophy and weakness. Using adeno-associated virus
      mediated gene transfer, we evaluated the potential to improve skeletal muscle
      weakness via systemic, postnatal inhibition of either myostatin or all signaling
      via the activin receptor type IIB (ActRIIB). After demonstrating elevated p-SMAD3
      content and differential content of ActRIIB ligands, 4-week-old male C/C SMA
      model mice were treated intraperitoneally with 1x1012 genome copies of pseudotype
      2/8 virus encoding a soluble form of the ActRIIB extracellular domain (sActRIIB)
      or protease-resistant myostatin propeptide (dnMstn) driven by a liver specific
      promoter. At 12 weeks of age, muscle mass and function were improved in treated
      C/C mice by both treatments, compared to controls. The fast fiber type muscles
      had a greater response to treatment than did slow muscles, and the greatest
      therapeutic effects were found with sActRIIB treatment. Myostatin/activin
      inhibition, however, did not rescue C/C mice from the reduction in motor unit
      numbers of the tibialis anterior muscle. Collectively, this study indicates that
      myostatin/activin inhibition represents a potential therapeutic strategy to
      increase muscle mass and strength, but not neuromuscular junction defects, in
      less severe forms of SMA.

PMID- 27870894
TI  - Identification of Stages of Erythroid Differentiation in Bone Marrow and
      Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in
      Autoimmune Hemolytic Anemia in Mouse.
AB  - Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic
      anemia (AIHA) in C57BL/6 mice after 5-6 weeks. Using the double in vivo
      biotinylation (DIB) technique, recently developed in our laboratory, turnover of
      erythrocyte cohorts of different age groups during AIHA was monitored. Results
      indicate a significant decline in the proportion of reticulocytes, young and
      intermediate age groups of erythrocytes, but a significant increase in the
      proportion of old erythrocytes in blood circulation. Binding of the autoantibody
      was relatively higher to the young erythrocytes and higher levels of
      intracellular reactive oxygen species (ROS) were also seen in these cells.
      Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice
      was examined by monitoring the relative proportion of erythroid cells at various
      stages of differentiation in these organs. Cells at different stages of
      differentiation were enumerated flow cytometrically by double staining with anti
      Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Erythroid
      cells in bone marrow declined significantly in AIHA induced mice, erythroblast C
      being most affected (50% decline). Erythroblast C also recorded high
      intracellular ROS level along with increased levels of membrane-bound
      autoantibody. No such decline was observed in spleen. A model of AIHA has been
      proposed indicating that binding of autoantibodies may not be a sufficient
      condition for destruction of erythroid cells in bone marrow and in blood
      circulation. Last stage of erythropoietic differentiation in bone marrow and
      early stages of erythrocytes in blood circulation are specifically susceptible to
      removal in AIHA.

PMID- 27870895
TI  - Simulated Respiratory Secretion for Use in the Development of Influenza
      Diagnostic Assays.
AB  - Many assays have been developed for the detection of influenza virus which is an
      important respiratory pathogen. Development of these assays commonly involves the
      use of human clinical samples for validation of their performance. However,
      clinical samples can be difficult to obtain, deteriorate over time, and be
      inconsistent in composition. The goal of this study was to develop a simulated
      respiratory secretion (SRS) that could act as a surrogate for clinical samples.
      To this end, we determined the effects major respiratory secretion components
      (Na+, K+, Ca2+, cells, albumin IgG, IgM, and mucin) have on the performance of
      influenza assays including both nucleic acid amplification and rapid antigen
      assays. Minimal effects on the molecular assays were observed for all of the
      components tested, except for serum derived human IgG, which suppressed the
      signal of the rapid antigen assays. Using dot blots we were able to show anti
      influenza nucleoprotein IgG antibodies are common in human respiratory samples.
      We composed a SRS that contained mid-point levels of human respiratory sample
      components and studied its effect compared to phosphate buffered saline and virus
      negative clinical sample matrix on the Veritor, Sofia, CDC RT-PCR, Simplexa,
      cobas Liat, and Alere i influenza assays. Our results demonstrated that a SRS can
      interact with a variety of test methods in a similar manner to clinical samples
      with a similar impact on test performance.

PMID- 27870897
TI  - A Forest Tent Caterpillar Outbreak Increased Resource Levels and Seedling Growth
      in a Northern Hardwood Forest.
AB  - In closed-canopy forests, gap formation and closure are thought to be major
      drivers of forest dynamics. Crown defoliation by insects, however, may also
      influence understory resource levels and thus forest dynamics. We evaluate the
      effect of a forest tent caterpillar outbreak on understory light availability,
      soil nutrient levels and tree seedling height growth in six sites with
      contrasting levels of canopy defoliation in a hardwood forest in northern lower
      Michigan. We compared resource levels and seedling growth of six hardwood species
      before, during and in the three years after the outbreak (2008-2012). Canopy
      openness increased strongly during the forest tent caterpillar outbreak in the
      four moderately and severely defoliated sites, but not in lightly defoliated
      sites. Total inorganic soil nitrogen concentrations increased in response to the
      outbreak in moderately and severely defoliated sites. The increase in total
      inorganic soil nitrogen was driven by a strong increase in soil nitrate, and
      tended to become stronger with increasing site defoliation. Seedling height
      growth increased for all species in the moderately and severely defoliated sites,
      but not in lightly defoliated sites, either during the outbreak year or in the
      year after the outbreak. Growth increases did not become stronger with increasing
      site defoliation, but were strongest in a moderately defoliated site with high
      soil nutrient levels. Growth increases tended to be strongest for the shade
      intolerant species Fraxinus americana and Prunus serotina, and the shade tolerant
      species Ostrya virginiana. The strong growth response of F. americana and P.
      serotina suggests that recurring forest tent caterpillar outbreaks may facilitate
      the persistence of shade intolerant species in the understory in the absence of
      canopy gaps. Overall, our results suggest that recurrent canopy defoliation
      resulting from cyclical forest insect outbreaks may be an additional driver of
      dynamics in temperate closed-canopy forests.

PMID- 27870896
TI  - M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration
      Induced by Corticosterone in the Hippocampus.
AB  - Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the
      turnover and homeostasis of monoamine neurotransmitters; yet, its
      pathophysiological role in monoamine deficiency, oxidative stress and
      neuroinflammation remains controversial. Protective effects of M30, a brain
      selective MAO inhibitor with iron-chelating antioxidant properties, have been
      shown in models of neurodegenerative diseases. This study aims to examine the
      neuroprotective mechanism of M30 against depressive-like behavior induced by
      corticosterone (CORT). Sprague-Dawley rats were given CORT subcutaneous
      injections with or without concomitant M30 administration for two weeks. CORT
      treated rats exhibited depressive-like behavior with significant elevated levels
      of MAO activities, serotonin turnover, oxidative stress, neuroinflammation and
      apoptosis in the hippocampus with significant losses of synaptic proteins when
      compared to the control. The expression and activity of cytokine-responsive
      indoleamine 2,3-dioxygenase (IDO-1), a catabolic enzyme of serotonin and
      tryptophan, was significantly increased in the CORT-treated group with lowered
      levels of serotonin. Besides, CORT markedly reduced dendritic length and spine
      density. Remarkably, M30 administration neutralized the aberrant changes in the
      hippocampus and prevented the induction of depressive-like behavior induced by
      CORT. Our results suggest that M30 is neuroprotective against CORT-induced
      depression targeting elevated MAO activities that cause oxidative stress and
      neuroinflammation, resulting in IDO-1 activation, serotonin deficiency and
      neurodegeneration.

PMID- 27870898
TI  - Functional Tissue Analysis Reveals Successful Cryopreservation of Human
      Osteoarthritic Synovium.
AB  - Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and is
      the most common form of arthritis worldwide. One third of OA patients have severe
      synovitis and less than 10% have no evidence of synovitis. Moreover, synovitis is
      predictive for more severe disease progression. This offers a target for therapy
      but more research on the pathophysiological processes in the synovial tissue of
      these patients is needed. Functional studies performed with synovial tissue will
      be more approachable when this material, that becomes available by joint
      replacement surgery, can be stored for later use. We set out to determine the
      consequences of slow-freezing of human OA synovial tissue. Therefore, we
      validated a method that can be applied in every routine laboratory and performed
      a comparative study of five cryoprotective agent (CPA) solutions. To determine
      possible deleterious cryopreservation-thaw effects on viability, the synovial
      tissue architecture, metabolic activity, RNA quality, expression of
      cryopreservation associated stress genes, and expression of OA characteristic
      disease genes was studied. Furthermore, the biological activity of the
      cryopreserved tissue was determined by measuring cytokine secretion induced by
      the TLR ligands lipopolysaccharides and Pam3Cys. Compared to non frozen synovium,
      no difference in cell and tissue morphology could be identified in the conditions
      using the CS10, standard and CryoSFM CPA solution for cryopreservation. However,
      we observed significantly lower preservation of tissue morphology with the
      Biofreeze and CS2 media. The other viability assays showed trends in the same
      direction but were not sensitive enough to detect significant differences between
      conditions. In all assays tested a clearly lower viability was detected in the
      condition in which synovium was frozen without CPA solution. This detailed
      analysis showed that OA synovial tissue explants can be cryopreserved while
      maintaining the morphology, viability and phenotypical response after thawing,
      offering enhanced opportunities for human in vitro studies.

PMID- 27870899
TI  - The Association between the Urinary Excretion of Trimethylselenonium and
      Trimethylsulfonium in Humans.
AB  - Hydrogen sulfide is a signaling molecule that plays important roles in several
      physiological processes, and its methylation product trimethylsulfonium (TMS) is
      a natural constituent of human urine that could serve as a biomarker for hydrogen
      sulfide. In vitro studies showed that the enzyme indole-ethylamine N
      methyltransferase (INMT) is responsible for the production of trimethylsulfonium
      as well as its selenium analogue trimethylselenonium (TMSe). Marked inter
      individual variability in TMSe production is associated with genetic
      polymorphisms in the INMT gene, but it remains unclear whether these
      polymorphisms affect substrate specificity or general enzymatic activity.
      Therefore, we explore the association between the TMS and TMSe production
      phenotypes. Caucasian volunteers were recruited and grouped according to their
      TMSe status into "TMSe producers" and "TMSe non-producers", and morning urine
      samples were collected over 5 consecutive days from each volunteer. A total of
      125 urine samples collected from 25 volunteers (13 TMSe producers and 12 TMSe non
      producers) were analyzed for total selenium and total sulfur using inductively
      coupled plasma mass spectrometry (ICPMS), trimethylselenonium using HPLC/ICPMS,
      and trimethylsulfonium using HPLC/electrospray ionization-triple quadrupole-mass
      spectrometry (ESI-QQQ-MS). Although there was no correlation between TMS and TMSe
      urinary levels within the "TMSe producers" group, the "TMSe producers" had
      urinary levels of TMS 10-fold higher than those of the "TMSe non-producers" (P <
      0.001). This result indicates that stratification according to TMSe status or
      genotype is crucial for the correct interpretation of urinary TMS as a possible
      biomarker for hydrogen sulfide body pools.

PMID- 27870900
TI  - To Fear Is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI
      Patients and Healthy Controls.
AB  - Fear is an important emotional reaction that guides decision making in situations
      of ambiguity or uncertainty. Both recognition of facial expressions of fear and
      decision making ability can be impaired after traumatic brain injury (TBI), in
      particular when the frontal lobe is damaged. So far, it has not been investigated
      how recognition of fear influences risk behavior in healthy subjects and TBI
      patients. The ability to recognize fear is thought to be related to the ability
      to experience fear and to use it as a warning signal to guide decision making. We
      hypothesized that a better ability to recognize fear would be related to a better
      regulation of risk behavior, with healthy controls outperforming TBI patients. To
      investigate this, 59 healthy subjects and 49 TBI patients were assessed with a
      test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests)
      and a gambling task (Iowa Gambling Task (IGT)). The results showed that,
      regardless of post traumatic amnesia duration or the presence of frontal lesions,
      patients were more impaired than healthy controls on both fear recognition and
      decision making. In both groups, a significant relationship was found between
      better fear recognition, the development of an advantageous strategy across the
      IGT and less risk behavior in the last blocks of the IGT. Educational level
      moderated this relationship in the final block of the IGT. This study has
      important clinical implications, indicating that impaired decision making and
      risk behavior after TBI can be preceded by deficits in the processing of fear.

PMID- 27870901
TI  - Ubiquitin-Dependent Modification of Skeletal Muscle by the Parasitic Nematode,
      Trichinella spiralis.
AB  - Trichinella spiralis is a muscle-specific parasitic worm that is uniquely
      intracellular. T. spiralis reprograms terminally differentiated skeletal muscle
      cells causing them to de-differentiate and re-enter the cell cycle, a process
      that cannot occur naturally in mammalian skeletal muscle cells, but one that
      holds great therapeutic potential. Although the host ubiquitin pathway is a
      common target for viruses and bacteria during infection, its role in parasite
      pathogenesis has been largely overlooked. Here we demonstrate that the secreted
      proteins of T. spiralis contain E2 Ub-conjugating and E3 Ub-ligase activity. The
      E2 activity is attributed to TsUBE2L3, a novel and conserved T. spiralis enzyme
      located in the secretory organ of the parasite during the muscle stages of
      infection. TsUBE2L3 cannot function with any T.spiralis secreted E3, but
      specifically binds to a panel of human RING E3 ligases, including the RBR E3
      ARIH2 with which it interacts with a higher affinity than the mammalian ortholog
      UbcH7/UBE2L3. Expression of TsUBE2L3 in skeletal muscle cells causes a global
      downregulation in protein ubiquitination, most predominantly affecting motor,
      sarcomeric and extracellular matrix proteins, thus mediating their stabilization
      with regards to proteasomal degradation. This effect is not observed in the
      presence of the mammalian ortholog, suggesting functional divergence in the
      evolution of the parasite protein. These findings demonstrate the first example
      of host-parasite interactions via a parasite-derived Ub conjugating enzyme; an E2
      that demonstrates a novel muscle protein stabilization function.

PMID- 27870904
TI  - Correction: Deleterious Rare Variants Reveal Risk for Loss of GABAA Receptor
      Function in Patients with Genetic Epilepsy and in the General Population.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0162883.].

PMID- 27870902
TI  - Sleep Duration, Exercise, Shift Work and Polycystic Ovarian Syndrome-Related
      Outcomes in a Healthy Population: A Cross-Sectional Study.
AB  - CONTEXT: Few studies have examined the associations between sleep duration,
      shiftwork, and exercise to the infrequent menstruation, hyperandrogenism, and
      ovarian morphological changes observed in women with polycystic ovarian syndrome
      (PCOS). OBJECTIVE: To examine whether lifestyle factors, including short sleep
      duration, insufficient exercise, and shiftwork, alone or in combination, are
      associated with the reproductive and metabolic abnormalities typical of PCOS in a
      healthy population. STUDY DESIGN, SIZE, DURATION: Prospective cross-sectional
      study of 231 women, including healthcare workers recruited for an annual health
      screen, healthy referral patients from the Women's Clinic and volunteers from the
      university community at the National University Hospital, Singapore, from 2011 to
      2015. MAIN OUTCOME MEASURES: The women completed a questionnaire, including their
      menstrual cycle length, sleep length, frequency of exercise and shift work.
      Hyperandrogenism (hirsutism score, testosterone, sex hormone binding globulin
      (SHBG)), ovarian morphology and function (anthral follicle count, ovarian volume,
      anti-mullerian hormone (AMH)), and metabolic measures (body mass index (BMI),
      waist hip ratio (WHR), blood pressure, fasting glucose, fasting insulin and
      fasting lipids) were examined through anthropometric measurements, transvaginal
      ultrasound scans, and blood tests. RESULTS: No significant associations were
      observed between shift work, exercise or sleep duration and the androgenic and
      ovarian measures that define PCOS. However, women reporting fewer than 6 hours of
      sleep were more likely to report abnormal (short or long) menstrual cycle lengths
      (OR = 2.1; 95% CI, 1.1 to 4.2). Women who reported fewer than 6 hours of sleep
      had increased fasting insulin levels (difference in means = 2.13; 95% CI, 0.27 to
      3.99 mU/L) and higher odds of insulin resistance (OR = 2.58; CI, 1.16 to 5.76).
      Lack of regular exercise was associated with higher mean fasting insulin
      (difference in means = 2.3 mU/L; 95% CI, 0.5 to 4.1) and HOMA-IR (difference in
      means = 0.49; 95% CI, 0.09 to 0.90) levels. CONCLUSIONS: Women with insufficient
      sleep are at increased risk of menstrual disturbances and insulin resistance, but
      do not have the hyperandrogenism and polycystic ovarian morphology typical of
      PCOS. WIDER IMPLICATIONS OF THE FINDINGS: Improved sleep duration may help reduce
      the risks of diabetes or infertility. Shift work, exercise or sleep duration
      appear not to impact the androgenic and ovarian measures that define PCOS.

PMID- 27870903
TI  - rDNA Loci Evolution in the Genus Glechoma (Lamiaceae).
AB  - Glechoma L. (Lamiaceae) is distributed in eastern Asia and Europe. Understanding
      chromosome evolution in Glechoma has been strongly hampered by its small
      chromosomes, constant karyotype and polyploidy. Here phylogenetic patterns and
      chromosomal variation in Glechoma species are considered, using genome sizes,
      chromosome mapping of 5S and 35S rDNAs by fluorescence in situ hybridisation
      (FISH), and phylogenetic analyses of internal transcribed spacers (nrITS) of 35S
      rDNA and 5S rDNA NTS sequences. Species and populations of Glechoma are
      tetraploid (2n = 36) with base chromosome number of x = 9. Four chromosomes carry
      pericentric 5S rDNA sites in their short arms in all the species. Two to four of
      these chromosomes also carry 35S rDNA in subterminal regions of the same arms.
      Two to four other chromosomes have 35S rDNA sites, all located subterminally
      within short arms; one individual possessed additional weak pericentric 35S rDNA
      signals on three other chromosomes. Five types of rDNA locus distribution have
      been defined on the basis of 35S rDNA variation, but none is species-specific,
      and most species have more than one type. Glechoma hederacea has four types.
      Genome size in Glechoma ranges from 0.80 to 0.94 pg (1C), with low levels of
      intrapopulational variation in all species. Phylogenetic analyses of ITS and NTS
      sequences distinguish three main clades coinciding with geographical
      distribution: European (G. hederacea-G. hirsuta), Chinese and Korean (G.
      longituba), and Japanese (G. grandis). The paper presents the first comparative
      cytogenetic analyses of Glechoma species including karyotype structure, rDNA
      location and number, and genome size interpreted in a phylogenetic context. The
      observed variation suggests that the genus is still in genomic flux. Genome size,
      but not rDNA loci number and distribution, provides a character for species
      delimitation which allows better inferences of interspecific relationships to be
      made, in the absence of well-defined morphological differentiation.

PMID- 27870905
TI  - Mapping QTL for Sex and Growth Traits in Salt-Tolerant Tilapia (Oreochromis spp.
      X O. mossambicus).
AB  - In aquaculture, growth and sex are economically important traits. To accelerate
      genetic improvement in increasing growth in salt-tolerant tilapia, we conducted
      QTL mapping for growth traits and sex with an F2 family, including 522 offspring
      and two parents. We used 144 polymorphic microsatellites evenly covering the
      genome of tilapia to genotype the family. QTL analyses were carried out using
      interval mapping for all individuals, males and females in the family,
      respectively. Using all individuals, three suggestive QTL for body weight, body
      length and body thickness respectively were detected in LG20, LG22 and LG12 and
      explained 2.4% to 3.1% of phenotypic variance (PV). When considering only males,
      five QTL for body weight were detected on five LGs, and explained 4.1 to 6.3% of
      PV. Using only females from the F2 family, three QTL for body weight were
      detected on LG1, LG6 and LG8, and explained 7.9-14.3% of PV. The QTL for body
      weight in males and females were located in different LGs, suggesting that in
      salt-tolerant tilapia, different set of genes 'switches' control the growth in
      males and females. QTL for sex were mapped on LG1 and LG22, indicating multigene
      sex determination in the salt-tolerant tilapia. This study provides new insights
      on the locations and effects of QTL for growth traits and sex, and sets the
      foundation for fine mapping for future marker-assisted selection for growth and
      sex in salt-tolerant tilapia aquaculture.

PMID- 27870907
TI  - National Survey Indicates that Individual Vaccination Decisions Respond
      Positively to Community Vaccination Rates.
AB  - Some models of vaccination behavior imply that an individual's willingness to
      vaccinate could be negatively correlated with the vaccination rate in her
      community. The rationale is that a higher community vaccination rate reduces the
      risk of contracting the vaccine-preventable disease and thus reduces the
      individual's incentive to vaccinate. At the same time, as for many health-related
      behaviors, individuals may want to conform to the vaccination behavior of peers,
      counteracting a reduced incentive to vaccinate due to herd immunity. Currently
      there is limited empirical evidence on how individual vaccination decisions
      respond to the vaccination decisions of peers. In the fall of 2014, we used a
      rapid survey technology to ask a large sample of U.S. adults about their
      willingness to use a vaccine for Ebola. Respondents expressed a greater
      inclination to use the vaccine in a hypothetical scenario with a high community
      vaccination rate. In particular, an increase in the community vaccination rate
      from 10% to 90% had the same impact on reported utilization as a nearly 50%
      reduction in out-of-pocket cost. These findings are consistent with a tendency to
      conform with vaccination among peers, and suggest that policies promoting
      vaccination could be more effective than has been recognized.

PMID- 27870906
TI  - Qualities of Life of Patients with Psychotic Disorders and Their Family
      Caregivers: Comparison between Hospitalised and Community-Based Treatment in
      Beijing, China.
AB  - BACKGROUND: Community healthcare in mainland China is still at an early stage.
      The qualities of life (QOLs) of patients with psychotic disorders undergoing
      rehabilitation in hospitals or in the community, as well as those of their
      caregivers, may differ from each other. OBJECTIVES: The study was performed to
      evaluate the QOL of patients with psychotic disorders and assess the differences
      in the QOLs between patients receiving care in diverse settings (hospital vs. the
      community). METHODS: This study was a descriptive study, in which all cases were
      collected from two psychiatric hospitals and five communities. Patients (n = 43)
      and caregivers (n = 40) in the psychiatric hospitals were grouped according to
      the length of illness and areas of residence and these criteria were also used to
      group patients (n = 55) and caregivers (n = 59) in the community. All
      participants were assessed using the WHOQOL-BREF (Chinese version). ANOVA was
      adopted to compare the QOL scores among the four groups (cases and caregivers in
      two settings), while confounding factors, such as age and marital status, were
      adjusted. RESULTS: Among the four groups of participants, namely, hospitalised
      and community patients and their corresponding caregivers, community samples had
      a significantly lower QOL score. The QOL score for the social relationships
      domain of the hospitalised patients' caregivers was significantly higher than
      that of the caregivers of community patients (P = 0.019). CONCLUSION: Community
      patients and their caregivers tend to have lower QOL scores than their
      hospitalised counterparts. The support of family members is urgently needed to
      provide better care for patients.

PMID- 27870908
TI  - N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for Loss of Muscle Mass
      in Prevalent Hemodialysis Patients.
AB  - Protein-energy wasting (PEW) is common in hemodialysis (HD) patients. A recent
      study demonstrated that a high level of N-terminal pro-B-type natriuretic peptide
      (NT-proBNP) may be associated with PEW in those patients. This prospective study
      aimed to assess the association of NT-proBNP with body composition and muscle
      loss. A cohort of prevalent HD patients (n = 238) was examined. Blood samples
      were obtained at baseline to measure high-sensitive C-reactive protein (hsCRP),
      interleukin-6 (IL-6), adiponectin and NT-proBNP. Nutritional status and changes
      in muscle mass were assessed by subjective global assessment, percentage
      creatinine generation rate (%CGR), creatinine index (CI) and lean body mass (LBM)
      estimated by dual-energy X-ray absorptiometry (DXA). The %CGR and CI were
      calculated five times for one year, and DXA was performed at baseline and one
      year later. Cardiac function was estimated by ultrasonography at baseline. NT
      proBNP was significantly higher in HD patients with PEW. High NT-proBNP was
      associated with cardiac dysfunction, increased levels of hsCRP and IL-6, and
      serially decreased levels of the indexes for muscle mass. Multiple regression
      analysis adjusted with confounders showed that NT-proBNP was an independent
      predictor for decrease in LBM and serial lower levels of %CGR and CI. In
      conclusion, the present study demonstrated a novel association between NT-proBNP
      and muscle loss. NT-proBNP may be an independent biomarker for malnutrition in HD
      patients, especially in patients with muscles loss, regardless of chronic
      inflammation, cardiac dysfunction, or overhydration.

PMID- 27870909
TI  - Variability of Rheotaxis Behaviors in Larval Bullfrogs Highlights Species
      Diversity in Lateral Line Function.
AB  - The morphology and distribution of lateral line neuromasts vary between
      ecomorphological types of anuran tadpoles, but little is known about how this
      structural variability contributes to differences in lateral-line mediated
      behaviors. Previous research identified distinct differences in one such
      behavior, positive rheotaxis towards the source of a flow, in two tadpole
      species, the African clawed frog (Xenopus laevis; type 1) and the American
      bullfrog (Rana catesbeiana; type 4). Because these two species had been tested
      under different flow conditions, we re-evaluated these findings by quantifying
      flow-sensing behaviors of bullfrog tadpoles in the same flow field in which X.
      laevis tadpoles had been tested previously. Early larval bullfrog tadpoles were
      exposed to flow in the dark, in the presence of a discrete light cue, and after
      treatment with the ototoxin gentamicin. In response to flow, tadpoles moved
      downstream, closer to a side wall, and higher in the water column, but they did
      not station-hold. Tadpoles exhibited positive rheotaxis, but with long latencies,
      low to moderate accuracy, and considerable individual variability. This is in
      contrast to the robust, stereotyped station-holding and accurate rheotaxis of X.
      laevis tadpoles. The presence of a discrete visual cue and gentamicin treatment
      altered spatial positioning and disrupted rheotaxis in both tadpole species.
      Species differences in lateral-line mediated behaviors may reflect differences in
      neuromast number and distribution, life history, or perceptual salience of other
      environmental cues.

PMID- 27870911
TI  - Long-Range Epistasis Mediated by Structural Change in a Model of Ligand Binding
      Proteins.
AB  - Recent analyses of amino acid mutations in proteins reveal that mutations at many
      pairs of sites are epistatic-i.e., their effects on fitness are non-additive-the
      combined effect of two mutations being significantly larger or smaller than the
      sum of their effects considered independently. Interestingly, epistatic sites are
      not necessarily near each other in the folded structure of a protein, and may
      even be located on opposite sides of a molecule. However, the mechanistic reasons
      for long-range epistasis remain obscure. Here, we study long-range epistasis in
      proteins using a previously developed model in which off-lattice polymers are
      evolved under ligand binding constraints. Epistatic effects in the model are
      qualitatively similar to those recently reported for small proteins, and many are
      long-range. We find that a major reason for long-range epistasis is
      conformational change-a recurrent theme in both positive and negative epistasis
      being the transfer, or exchange of material between the ordered nucleus, which
      supports the binding site, and the liquid-like surface of a folded molecule.
      These local transitions in phase and folded structure are largely responsible for
      long-range epistasis in our model.

PMID- 27870910
TI  - In Obesity, HPA Axis Activity Does Not Increase with BMI, but Declines with
      Aging: A Meta-Analysis of Clinical Studies.
AB  - BACKGROUND: Obesity is one of the major public health challenges worldwide. It
      involves numerous endocrine disorders as etiological factors or as complications.
      Previous studies strongly suggested the involvement of the hypothalamic-pituitary
      adrenal (HPA) axis activity in obesity, however, to date, no consistent trend in
      obesity-associated alterations of the HPA axis has been identified. Aging has
      been demonstrated to aggravate obesity and to induce abnormalities of the HPA
      axis. Thus, the question arises whether obesity is correlated with peripheral
      indicators of HPA function in adult populations. OBJECTIVES: We aimed to meta
      analyze literature data on peripheral cortisol levels as indicators of HPA
      activity in obesity during aging, in order to identify possible explanations for
      previous contradictory findings and to suggest new approaches for future clinical
      studies. DATA SOURCES: 3,596 records were identified through searching of PubMed,
      Embase and Cochrane Library Database. Altogether 26 articles were suitable for
      analyses. STUDY ELIGIBILITY CRITERIA: Empirical research papers were eligible
      provided that they reported data of healthy adult individuals, included body mass
      index (BMI) and measured at least one relevant peripheral cortisol parameter
      (i.e., either morning blood cortisol or 24-h urinary free cortisol). STATISTICAL
      METHODS: We used random effect models in each of the meta-analyses calculating
      with the DerSimonian and Laird weighting methods. I-squared indicator and Q test
      were performed to assess heterogeneity. Meta-regression was applied to explore
      the effect of BMI and age on morning blood and urinary free cortisol levels. To
      assess publication bias Egger's test was used. RESULTS: Obesity did not show any
      correlation with the studied peripheral cortisol values. On the other hand,
      peripheral cortisol levels declined with aging within the obese, but not in the
      non-obese groups. CONCLUSIONS: Our analysis demonstrated that obesity or healthy
      aging does not lead to enhanced HPA axis activity, peripheral cortisol levels
      rather decline with aging.

PMID- 27870913
TI  - Genomic Contributors to Rhythm Outcome of Atrial Fibrillation Catheter Ablation -
      Pathway Enrichment Analysis of GWAS Data.
AB  - BACKGROUND: Left atrial enlargement and persistent atrial fibrillation (AF) are
      well-known predictors for arrhythmia recurrence after AF catheter ablation
      (LRAF). In this study, by using pathway enrichment analysis of GWAS data, we
      tested the hypothesis that genetic pathways associated with these phenotypes are
      also associated with LRAF. METHODS: Samples from 660 patients with paroxysmal (n
      = 370) or persistent AF (n = 290) undergoing de-novo AF catheter ablation were
      genotyped for ~1,000,000 SNPs. SNPs found to be significantly associated with
      left atrial diameter (LAD) or AF type were used for gene-based association tests
      in a systematic biological Knowledge-based mining system for Genome-wide Genetic
      studies (KGG). Associated genes were tested for pathway enrichment using WEB
      based Gene SeT AnaLysis Toolkit (WebGestalt), the Gene Annotation Tool to Help
      Explain Relationships (GATHER) and the databases provided by Kyoto Encyclopedia
      of Genes and Genomes (KEGG). In a second step, the association of consistently
      enriched pathways and LRAF was tested. RESULTS: By using sequential 7-day Holter
      ECGs, LRAF between 3 and 12 months was observed in 48% and was associated with
      LAD (B = 1.801, 95% CI 0.760-2.841, p = 1.0E-3) and persistent AF (OR = 2.1; 95%
      CI 1.567-2.931, p = 2.0E-6). WebGestalt (adj. p = 2.7E-22) and GATHER (adj. p =
      5.2E-3) identified the calcium signaling pathway (hsa04020) as the only
      consistently enriched pathway for LAD, while the extracellular matrix (ECM) 
      receptor interaction pathway (hsa04512) was the only consistently enriched
      pathway for AF type (adj. p = 2.1E-15 in WebGestalt; adj. p = 9.3E-4 in GATHER).
      Both calcium signaling (adj. p = 2.2E-17 in WebGestalt; adj. p = 2.9E-2 in
      GATHER) and ECM-receptor interaction (adj. p = 1.2E-10 in WebGestalt; adj. p =
      2.9E-2 in GATHER) were significantly associated with LRAF. CONCLUSIONS: Calcium
      signaling and ECM-receptor interaction pathways are associated with LAD and AF
      type and, in turn, with LRAF. Future and larger studies are necessary to
      replicate and apply these findings.

PMID- 27870912
TI  - ATP Hydrolysis Induced Conformational Changes in the Vitamin B12 Transporter
      BtuCD Revealed by MD Simulations.
AB  - ATP binding cassette (ABC) transporters utilize the energy of ATP hydrolysis to
      uni-directionally transport substrates across cell membrane. ATP hydrolysis
      occurs at the nucleotide-binding domain (NBD) dimer interface of ABC
      transporters, whereas substrate translocation takes place at the translocation
      pathway between the transmembrane domains (TMDs), which is more than 30 angstroms
      away from the NBD dimer interface. This raises the question of how the hydrolysis
      energy released at NBDs is "transmitted" to trigger the conformational changes at
      TMDs. Using molecular dynamics (MD) simulations, we studied the post-hydrolysis
      state of the vitamin B12 importer BtuCD. Totally 3-MUs MD trajectories
      demonstrate a predominantly asymmetric arrangement of the NBD dimer interface,
      with the ADP-bound site disrupted and the ATP-bound site preserved in most of the
      trajectories. TMDs response to ATP hydrolysis by separation of the L-loops and
      opening of the cytoplasmic gate II, indicating that hydrolysis of one ATP could
      facilitate substrate translocation by opening the cytoplasmic end of
      translocation pathway. It was also found that motions of the L-loops and the
      cytoplasmic gate II are coupled with each other through a contiguous interaction
      network involving a conserved Asn83 on the extended stretch preceding TM3 helix
      plus the cytoplasmic end of TM2/6/7 helix bundle. These findings entail a TMD-NBD
      communication mechanism for type II ABC importers.

PMID- 27870915
TI  - Effects of Angiopoietin-2 on Transplanted Mouse Ovarian Tissue.
AB  - Transplantation of ovarian tissue (OT) is currently the only clinical option to
      restore fertility with cryopreserved OT. However, follicle loss caused by
      ischemia and slow revascularization occurs in transplanted OT. To shorten the
      ischemic period and promote angiogenesis, some angiogenic factors have been used.
      Angiopoietin-2 (Ang2) is one of the major angiogenic factors and has been
      reported to promote blood vessels and increase vascular permeability in ischemic
      and/or hypoxic environment. This study was performed to investigate the effects
      of Ang2 on follicle integrity and revascularization of transplanted mouse OT.
      Five-week-old B6D2F1 female mice were divided into a control group and two Ang2
      groups, followed by ovary collection and vitrification. After warming, the
      ovaries were autotransplanted into kidney capsules with/without Ang2 injection
      (50 or 500 ng/kg), and then the mice were sacrificed at days 2, 7, 21, and 42
      after transplantation. A total 2,437 follicles in OT grafts were assessed for
      follicular density, integrity, and classification by using hematoxylin and eosin
      staining. Apoptosis and revascularization were evaluated by using TUNEL assay and
      CD31 immunohistochemistry, respectively. Serum follicle-stimulating hormone (FSH)
      levels were measured by using enzyme-linked immunosorbent assay. Both Ang2 groups
      showed remarkable increase in morphologically intact follicle ratio across all
      grafting durations except D21. The numbers of CD31(+) vessels were significantly
      increased in both Ang2 groups compared with the control group at all durations,
      except in the 50 ng Ang2 group at D42. However, the mean numbers of follicles of
      the grafts, apoptosis ratios, and serum FSH levels showed no significant
      differences among the groups. Our results show that Ang2 treatment significantly
      increased the intact follicle ratios and the number of blood vessels of the mouse
      OT grafts. However, further studies performed with large animal or human OT are
      necessary before clinical application for fertility preservation in cancer
      patients, and the reliability of the systemic effects of Ang2 should be verified.

PMID- 27870914
TI  - Transgenic Bt Cotton Does Not Disrupt the Top-Down Forces Regulating the Cotton
      Aphid in Central China.
AB  - Top-down force is referred to arthropod pest management delivered by the
      organisms from higher trophic levels. In the context of prevalent adoption of
      transgenic Bt crops that produce insecticidal Cry proteins derived from Bacillus
      thuringiensis (Bt), it still remains elusive whether the top-down forces are
      affected by the insect-resistant traits that introduced into the Bt crops. We
      explored how Bt cotton affect the strength of top-down forces via arthropod
      natural enemies in regulating a non-target pest species, the cotton aphid Aphis
      gossypii Glover, using a comparative approach (i.e. Bt cotton vs. conventional
      cotton) under field conditions. To determine top-down forces, we manipulated
      predation/parasitism exposure of the aphid to their natural enemies using
      exclusion cages. We found that the aphid population growth was strongly
      suppressed by the dominant natural enemies including Coccinellids, spiders and
      Aphidiines parasitoids. Coccinellids, spiders and the assemblage of other
      arthropod natural enemies (mainly lacewings and Hemipteran bugs) are similarly
      abundant in both plots, but with the parasitoid mummies less abundant in Bt
      cotton plots compared to the conventional cotton plots. However, the lower
      abundance of parasitoids in Bt cotton plots alone did not translate into
      differential top-down control on A. gossypii populations compared to conventional
      ones. Overall, the top-down forces were equally strong in both plots. We conclude
      that transgenic Bt cotton does not disrupt the top-down forces regulating the
      cotton aphid in central China.

PMID- 27870917
TI  - Combating Rhino Horn Trafficking: The Need to Disrupt Criminal Networks.
AB  - The onslaught on the World's wildlife continues despite numerous initiatives
      aimed at curbing it. We build a model that integrates rhino horn trade with rhino
      population dynamics in order to evaluate the impact of various management
      policies on rhino sustainability. In our model, an agent-based sub-model of horn
      trade from the poaching event up through a purchase of rhino horn in Asia impacts
      rhino abundance. A data-validated, individual-based sub-model of the rhino
      population of South Africa provides these abundance values. We evaluate policies
      that consist of different combinations of legal trade initiatives, demand
      reduction marketing campaigns, increased anti-poaching measures within protected
      areas, and transnational policing initiatives aimed at disrupting those criminal
      syndicates engaged in horn trafficking. Simulation runs of our model over the
      next 35 years produces a sustainable rhino population under only one management
      policy. This policy includes both a transnational policing effort aimed at
      dismantling those criminal networks engaged in rhino horn trafficking-coupled
      with increases in legal economic opportunities for people living next to
      protected areas where rhinos live. This multi-faceted approach should be the
      focus of the international debate on strategies to combat the current slaughter
      of rhino rather than the binary debate about whether rhino horn trade should be
      legalized. This approach to the evaluation of wildlife management policies may be
      useful to apply to other species threatened by wildlife trafficking.

PMID- 27870916
TI  - Quantitative Trait Locus Analysis of Late Leaf Spot Resistance and Plant-Type
      Related Traits in Cultivated Peanut (Arachis hypogaea L.) under Multi
      Environments.
AB  - Late leaf spot (LLS) is one of the most serious foliar diseases affecting peanut
      worldwide leading to huge yield loss. To understand the genetic basis of LLS and
      assist breeding in the future, we conducted quantitative trait locus (QTL)
      analysis for LLS and three plant-type-related traits including height of main
      stem (HMS), length of the longest branch (LLB) and total number of branches
      (TNB). Significant negative correlations were observed between LLS and the plant
      type-related traits in multi-environments of a RIL population from the cross
      Zhonghua 5 and ICGV 86699. A total of 20 QTLs were identified for LLS, of which
      two QTLs were identified in multi-environments and six QTLs with phenotypic
      variation explained (PVE) more than 10%. Ten, seven, fifteen QTLs were identified
      for HMS, LLB and TNB, respectively. Of these, one, one, two consensus QTLs and
      three, two, three major QTLs were detected for HMS, LLB and TNB, respectively. Of
      all 52 unconditional QTLs for LLS and plant-type-related traits, 10 QTLs were
      clustered in five genetic regions, of which three clusters including five robust
      major QTLs overlapped between LLS and one of the plant-type-related traits,
      providing evidence that the correlation could be genetically constrained. On the
      other hand, conditional mapping revealed different numbers and different extent
      of additive effects of QTLs for LLS conditioned on three plant-type-related
      traits (HMS, LLB and TNB), which improved our understanding of interrelationship
      between LLS and plant-type-related traits at the QTL level. Furthermore, two
      QTLs, qLLSB6-7 and qLLSB1 for LLS resistance, were identified residing in two
      clusters of NB-LRR-encoding genes. This study not only provided new favorable
      QTLs for fine-mapping, but also suggested that the relationship between LLS and
      plant-type-related traits of HMS, LLB and TNB should be considered while breeding
      for improved LLS resistance in peanut.

PMID- 27870918
TI  - Time-Dependent Impact of Irreversible Electroporation on Pancreas, Liver, Blood
      Vessels and Nerves: A Systematic Review of Experimental Studies.
AB  - INTRODUCTION: Irreversible electroporation (IRE) is a novel ablation technique in
      the treatment of unresectable cancer. The non-thermal mechanism is thought to
      cause mostly apoptosis compared to necrosis in thermal techniques. Both in
      experimental and clinical studies, a waiting time between ablation and tissue or
      imaging analysis to allow for cell death through apoptosis, is often reported.
      However, the dynamics of the IRE effect over time remain unknown. Therefore, this
      study aims to summarize these effects in relation to the time between treatment
      and evaluation. METHODS: A systematic search was performed in Pubmed, Embase and
      the Cochrane Library for original articles using IRE on pancreas, liver or
      surrounding structures in animal or human studies. Data on pathology and time
      between IRE and evaluation were extracted. RESULTS: Of 2602 screened studies, 36
      could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood
      vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and
      rabbit). No eligible human studies were found. In liver and pancreas, the first
      signs of apoptosis and haemorrhage were observed 1-2 hours after treatment, and
      remained visible until 24 hours in liver and 7 days in pancreas after which the
      damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica
      media, intima and lumen remained unchanged for 24 hours. After 7 days,
      inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which
      persisted until 35 days. In nerves, the median time until demonstrable
      histological changes was 7 days. CONCLUSIONS: Tissue damage after IRE is a
      dynamic process with remarkable time differences between tissues in animals.
      Whereas pancreas and liver showed the first damages after 1-2 hours, this took 24
      hours in blood vessels and 7 days in nerves.

PMID- 27870921
TI  - Microthreaded Implants and Crestal Bone Loss: A Systematic Review.
AB  - This systematic literature review investigated the effect of microthreaded-neck
      dental implants on crestal bone loss. Using the participants, interventions,
      comparison groups, outcomes, and study design (PICO) system, we addressed the
      following focused question: Do microthreaded-neck dental implants positively
      affect the crestal bone level around dental implants? We searched 3 electronic
      databases to find articles published between January 1995 and June 2016 that
      contained any combination of the following keywords: dental implant, microthread,
      microthreaded, crestal bone level, crestal bone loss, and alveolar bone level. We
      excluded case reports, review articles, letters to the editor, commentaries, and
      articles published in a language other than English. We found a total of 70
      articles. After eliminating duplicates and applying PICO eligibility criteria, we
      selected only articles that reported the results of randomized controlled trials,
      prospective or retrospective cohort studies, case control studies, cross
      sectional studies, or other types of clinical trials that compared the
      microthreaded implant design with other implant designs. We were left with 23
      articles for review. The 23 articles reported crestal bone loss ranging from .05
      mm to .9 mm, with a range of 12 to 96 months of follow-up. Less crestal bone was
      lost with dental implants that had a microthreaded neck design than with machined
      surface or conventional rough-surface dental implants. Thus, microthreaded dental
      implants are a better choice than are implants with other designs. Future studies
      should use standardized imaging techniques to evaluate the placement of these
      implants in bone-augmented sites.

PMID- 27870922
TI  - Evaluating the benefits of vaccination when used in combination with stamping-out
      measures against hypothetical introductions of foot-and-mouth disease into New
      Zealand: a simulation study.
AB  - AIMS: To evaluate the benefits of vaccination against simulated outbreaks of foot
      and-mouth disease (FMD) in New Zealand, when applied as an additional measure to
      stamping-out. METHODS: A simulation modelling approach was used. The study
      population comprised all known farms in New Zealand with FMD-susceptible
      livestock. Infection was seeded into three different areas of New Zealand.
      Transmission mechanisms included direct and indirect contacts, local spread and
      airborne spread. Efficacies of some of the stamping-out measures were varied.
      Vaccination strategies involved different start times, size and type of
      vaccination zone, and species vaccinated. Personnel resources for vaccination
      were varied as was the herd immunity profile following vaccination. Altogether,
      336 models were specified, with 100 iterations conducted for each model.
      Generalised linear modelling and boosted regression trees were used to evaluate
      which variables had the biggest effect on the number of infected premises (IP),
      epidemic duration and area under control. RESULTS: Vaccination, when used as an
      adjunct to the standard stamping-out programme, significantly reduced the
      outbreak size. Vaccination reduced the median number of IP by 26 (95% CI=18-35),
      epidemic duration by 16 (95% CI=13-19) days and area under control by 474 (95%
      CI=250-699) km2 when there was no airborne spread; and when there was airborne
      spread the median reduction was 87 (95% CI=70-105) IP, 32 (95% CI=28-35) days and
      898 (95% CI=665-1139) km2, respectively. Multivariable analyses showed that
      starting vaccination 11 days after first detection of FMD produced greater
      benefits than starting 16 or 21 days after detection. Increasing vaccination
      zones resulted in increased benefits. Boosted regression tree analyses showed
      that the most influential variables on the outcome measures were interval to
      first detection, incursion location, whether there was airborne spread or not and
      herd immunity profile. CONCLUSIONS AND CLINICAL RELEVANCE: This study showed that
      there are benefits to the use of vaccination in combination with a stamping-out
      policy for control of FMD outbreaks under New Zealand conditions. The optimal
      vaccination strategy was identified as being a 3-5 km radius suppressive
      vaccination zone deployed between 11-16 days after first detection. Vaccination
      had a greater benefit during larger outbreaks, such as when there was airborne
      transmission. The key factors which were identified from this study will help
      inform New Zealand's competent authority on how best to deploy vaccination to
      further strengthen its approach to FMD eradication should New Zealand ever
      experience an outbreak.

PMID- 27870920
TI  - Picroside II Attenuates Airway Inflammation by Downregulating the Transcription
      Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic
      Asthma.
AB  - Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been
      used as traditional medicine to treat inflammatory diseases. In this study, we
      assessed whether picroside II has inhibitory effects on airway inflammation in a
      mouse model of house dust mite (HDM)-induced asthma. In the HDM-induced asthmatic
      model, picroside II significantly reduced inflammatory cell counts in the
      bronchoalveolar lavage fluid (BALF), the levels of total immunoglobulin (Ig) E
      and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus
      hypersecretion in the lung tissues. ELISA analysis showed that picroside II down
      regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13)
      and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNgamma
      in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes
      and the transcription factor GATA3 in the lung tissues of HDM-induced mice.
      Finally, we demonstrated that picroside II significantly decreased the expression
      of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo
      results. Taken together, these results indicate that picroside II has protective
      effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias.

PMID- 27870919
TI  - Cytomegalovirus Reinfections Stimulate CD8 T-Memory Inflation.
AB  - Cytomegalovirus (CMV) has been shown to induce large populations of CD8 T
      effector memory cells that unlike central memory persist in large quantities
      following infection, a phenomenon commonly termed "memory inflation". Although
      murine models to date have shown very large and persistent CMV-specific T-cell
      expansions following infection, there is considerable variability in CMV-specific
      T-memory responses in humans. Historically such memory inflation in humans has
      been assumed a consequence of reactivation events during the life of the host.
      Because basic information about CMV infection/re-infection and reactivation in
      immune competent humans is not available, we used a murine model to test how
      primary infection, reinfection, and reactivation stimuli influence memory
      inflation. We show that low titer infections induce "partial" memory inflation of
      both mCMV specific CD8 T-cells and antibody. We show further that reinfection
      with different strains can boost partial memory inflation. Finally, we show
      preliminary results suggesting that a single strong reactivation stimulus does
      not stimulate memory inflation. Altogether, our results suggest that while high
      titer primary infections can induce memory inflation, reinfections during the
      life of a host may be more important than previously appreciated.

PMID- 27870923
TI  - Covering the Implant Prosthesis Screw Access Hole: A Biological Approach to
      Material Selection and Technique.

PMID- 27870925
TI  - Quantitative and qualitative analysis of student tutors as near-peer teachers in
      the gross anatomy course.
AB  - INTRODUCTION: Peer teaching is a well-established teaching method in medical
      education. During the 2012/13 winter term, the Institute of Anatomy and Cell
      Biology in Ulm, Germany, introduced a longitudinal didactics program ("Train the
      Tutor": TtT) to train student tutors as near-peer teachers (NPT) in the
      dissection course (DC). Twenty-three of 38 tutors participated in the programme.
      Our study describes the educational concept and the NPTs' activities in the
      dissection course. METHODS: NPTs documented their activities on a daily basis in
      the form of semi-structured reports. A total of 575 reports were quantitatively
      and qualitatively analysed. Free-text analysis was performed using Grounded
      Theory followed by code quantification of all indications (n=1868). RESULTS: NPTs
      spend 61% of their time dissecting by themselves or supervising the tutee's
      dissection process. Organisational tasks had a larger share at the beginning of
      the course. Just before examinations the proportion of time spent giving feedback
      rose. Of all positive indications, 45% described experiences working with the
      tutees. In contrast, 68% of all negative indications were characterized by a self
      critical reflection on their own activities. NPTs included all learning domains
      in their teaching, substantially functioning as teachers and role models to
      convey particular attitudes. CONCLUSION: TtT-Trained Tutors (NPT) clearly met the
      requirements of a practical course and adjusted their activities in response to
      the course's progress. NPTs were concerned about their tutees' attitudes and may
      need more professional support within the TtT program regarding this.

PMID- 27870926
TI  - Rare Submandibular Presentation of Pediatric Castleman Disease: Case Report.
AB  - Castleman disease (CD), a benign lymphoproliferative disorder that affects lymph
      nodes, is uncommon in children, with only approximately 100 cases published.
      Although 23% of pediatric CD cases are found in the neck, there is no substantial
      reported percentage found in the salivary glands, especially the submandibular
      salivary gland (SMSG). A pediatric case of CD involving the SMSG is reported
      because of its extreme rarity.

PMID- 27870927
TI  - CD30 Induces Heat Shock Protein 90 and Signal Integration in Classic Hodgkin
      Lymphoma Cells.
AB  - Previous studies report deregulation of multiple signaling pathways in classic
      Hodgkin lymphoma (cHL) cells. However, the mechanisms of how these pathways are
      integrated are not fully understood. Herein, we show involvement of cHL hallmark
      antigen CD30 in this process. CD30 facilitates phosphorylation of heat shock
      factor 1, activates heat shock promoter element, and induces heat shock protein
      (HSP) 90. CD30 repression and subsequent inhibition of HSP90 suppresses NF
      kappaB, extracellular signal-regulated kinase, AKT, and STAT pathways in cHL cell
      lines. Thus, CD30-mediated induction of HSP90 appears to serve as a central hub
      for integration of intracellular signaling in cHL cells. We also show that CD30
      induces HSP90 through phosphorylation of heat shock factor 1 via c-Jun N-terminal
      kinase in cHL cells. Although anaplastic large-cell lymphoma (ALCL) also is
      associated with CD30 overexpression, our experiments reveal that HSP90 induction
      in ALCL-bearing nucleophosmin-anaplastic lymphoma kinase (ALK) does not depend on
      CD30 but instead on ALK via c-Jun N-terminal kinase. Together, these results
      highlight a novel role for CD30 in mediating integration of signaling pathways of
      cHL cells while being replaced in this function by ALK in ALCL cells.

PMID- 27870924
TI  - Evaluating mesenchymal stem cell therapy for sepsis with preclinical meta
      analyses prior to initiating a first-in-human trial.
AB  - Evaluation of preclinical evidence prior to initiating early-phase clinical
      studies has typically been performed by selecting individual studies in a non
      systematic process that may introduce bias. Thus, in preparation for a first-in
      human trial of mesenchymal stromal cells (MSCs) for septic shock, we applied
      systematic review methodology to evaluate all published preclinical evidence. We
      identified 20 controlled comparison experiments (980 animals from 18
      publications) of in vivo sepsis models. Meta-analysis demonstrated that MSC
      treatment of preclinical sepsis significantly reduced mortality over a range of
      experimental conditions (odds ratio 0.27, 95% confidence interval 0.18-0.40,
      latest timepoint reported for each study). Risk of bias was unclear as few
      studies described elements such as randomization and no studies included an
      appropriately calculated sample size. Moreover, the presence of publication bias
      resulted in a ~30% overestimate of effect and threats to validity limit the
      strength of our conclusions. This novel prospective application of systematic
      review methodology serves as a template to evaluate preclinical evidence prior to
      initiating first-in-human clinical studies.

PMID- 27870928
TI  - miR-182-5p Inhibition Ameliorates Ischemic Acute Kidney Injury.
AB  - Acute kidney injury (AKI) remains a major clinical event with high mortality
      rates. We previously identified renal miR-182 as the main driver of post
      transplantation AKI. Therefore, we tested the causal inference of miR-182 by
      inhibiting its renal expression in vivo. In 45 rats AKI was induced by right
      nephrectomy and contralateral clamping of the renal pedicle for 40 minutes.
      Systemically administered antisense oligonucleotide (ASO) inhibited miR-182 in
      the kidneys up to 96 hours. The maximum creatinine elevation was on day 2 after
      injury (mg/dL; median and interquartile range): ASO 2.5mg/kg: 1.9 (1.3; 3.2), ASO
      25mg/kg: 2.8 (0.7; 5.0), mismatch oligonucleotide (MM) 25mg/kg: 5.7 (5,0; 5.8),
      saline: 4.4 (3.5; 5.8) (P = 0.016, analysis of variance). Blinded
      semiquantitative histologic evaluation of renal biopsies showed better preserved
      morphology in both ASO groups than saline- and MM-treated kidneys (median and
      interquartile range of overall injury scores): ASO both concentrations 1 (1, 1),
      saline 3 (3, 3) and MM 3 (3, 3) (P< 0.001, analysis of variance). ASO facilitated
      cell proliferation, metabolism, and angiogenesis on a genome-wide level. ASO when
      applied in normothermic kidney machine perfusion reduced renal miR-182 expression
      by more than two magnitudes. In summary, we showed that in vivo inhibition of miR
      182 by ASO improved kidney function and morphology after AKI. This technique may
      be applicable to reduce the high rate of AKI in the human renal transplantation
      setting.

PMID- 27870929
TI  - A clinical study of cutaneous changes in pregnancy.
AB  - BACKGROUND/OBJECTIVE: Pregnant women experience a myriad of physiological and
      metabolic changes that affect different organ systems in the body. Cutaneous and
      appendageal alterations that manifest during pregnancy are largely modulated by
      hormonal, immunologic, and metabolic factors. Detailed reports encompassing
      physiological changes and specific dermatoses of pregnancy and effects of various
      dermatoses on pregnant women are scanty in literature. This study was conducted
      to examine in detail both physiological changes and specific dermatoses. The
      cutaneous changes are divided into physiological changes, skin diseases
      aggravated by pregnancy, and specific dermatoses of pregnancy. The objectives
      were to study the various cutaneous changes of pregnancy and to know the
      proportion of these cutaneous manifestations in pregnant women. METHODS: This
      study included 600 pregnant women attending the Obstetrics and Gynecology
      Department of a tertiary teaching hospital in Northern Kerala, India. Detailed
      history elicitation and complete physical and dermatological examination were
      performed. Skin biopsy was performed in relevant cases. RESULTS: Cutaneous
      changes were seen in a majority of patients, of which physiological changes were
      the most common (99%). The most common cutaneous manifestation was
      hyperpigmentation (526; 87.6%), followed by striae gravidarum (72.8%). Other
      changes were vascular, including pedal edema (10%), pregnancy gingivitis (1.8%),
      and varicose veins (1%). Infections were the common dermatological problem in
      this study group. The most common infections were vulvovaginal candidiasis (21%),
      Tinea versicolor (6%), scabies (2.8%), dermatophytosis (1.5%), and sexually
      transmitted infection (0.5%). Specific dermatoses were seen in 12 cases (2%),
      with the most common being pruritic urticarial papules and plaques of pregnancy
      (1.3%). CONCLUSION: Pregnant women are prone to suffer from a wide range of
      dermatological problems apart from specific dermatoses of pregnancy. The study
      emphasizes the need for a detailed and meticulous examination of these patients
      to detect these various disorders.

PMID- 27870930
TI  - Influence of membrane material on the production of colloidal emulsions by premix
      membrane emulsification.
AB  - Premix membrane emulsification is a possibility to produce colloidal emulsions as
      carrier systems for poorly water soluble drugs. During the extrusion of a coarse
      pre-emulsion through a porous membrane, the emulsion droplets are disrupted into
      smaller droplets. The influence of the membrane material on the emulsification
      success was investigated in dependence on the emulsifier. Premixed medium chain
      triglyceride (MCT) emulsions stabilized with five different emulsifiers were
      extruded through seven different hydrophilic polymeric membrane materials with
      pore sizes of 200nm. The resulting emulsions differed strongly in particle size
      and particle size distribution with a range of median particle sizes between
      0.08MUm and 11MUm. The particle size of the emulsions did not depend mainly on
      the structure or thickness of the membrane but on the combination of emulsifier
      and membrane material. Contact angle measurements indicated that the wetting of
      the membrane with the continuous phase of the emulsion was decisive for achieving
      emulsions with colloidal particle sizes. The type of dispersed phase was of minor
      importance as basically the same results were obtained with peanut oil instead of
      MCT. To prove the assumption that only sufficiently hydrophilic membrane
      materials led to emulsions with colloidal particle sizes, two membrane materials
      were hydrophilized by plasma treatment. After hydrophilization, the emulsifying
      process led to emulsions with smaller particle sizes. The use of an alumina
      membrane (Anodisc(r)) improved the process even more. With this type of membrane,
      emulsions with a median particle size below 250nm and a narrow particle size
      distribution could be obtained with all investigated emulsifiers.

PMID- 27870931
TI  - Effects of three diamides (chlorantraniliprole, cyantraniliprole and
      flubendiamide) on life history, embryonic development and oxidative stress
      biomarkers of Daphnia magna.
AB  - The diamides have become one of the most promising new classes of insecticides.
      In this study, we evaluated the toxicity of three diamides (chlorantraniliprole,
      cyantraniliprole and flubendiamide) to Daphnia magna. The acute toxicity test
      showed that the 48-h EC50 of chlorantraniliprole, cyantraniliprole and
      flubendiamide were 8.5, 23.9 and 63.5 MUg/L, respectively. Biochemical
      measurements revealed a significant increase in reactive oxygen species (ROS) in
      D. magna after acute exposure to the three diamides. A significant decrease in
      activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione
      peroxidase (GPx) was observed, which was consistent with the down-regulated
      transcription of antioxidant genes sod and gpx. Catalase (CAT) activity exhibited
      a significant increase while the related gene cat showed no obvious change in
      daphnids acutely exposed to the three diamides. The chronic test revealed that
      the three diamides could cause lethal and sub-lethal effects on daphnids within
      constricted range of concentrations at MUg/L level. The 21-d EC50 of
      chlorantraniliprole, cyantraniliprole and flubendiamide for mobility were 5.0,
      13.6 and 36.8 MUg/L, respectively. The chronic LOEC of chlorantraniliprole,
      cyantraniliprole and flubendiamide based on survival, growth and reproduction of
      D. magna were 4.05, 10.24 and 19.36 MUg/L, respectively. Moreover, these three
      diamides can induce severe developmental abnormalities in D. magna embryos
      including underdeveloped second antennae, curved tail spine and abnormal body
      region after acute exposure and the 48-h EC50 were 6.2, 14.1 and 30.8 MUg/L for
      chlorantraniliprole, cyantraniliprole and flubendiamide respectively. Our
      findings indicate that even low levels of diamides can pose ecological risks to
      aquatic ecosystems.

PMID- 27870932
TI  - Investigation of the toxicity of bismuth oxide nanoparticles in various cell
      lines.
AB  - Nanoparticles have been drawn attention in various fields ranging from medicine
      to industry because of their physicochemical properties and functions, which lead
      to extensive human exposure to nanoparticles. Bismuth (Bi)-based compounds have
      been commonly used in the industrial, cosmetic and medical applications. Although
      the toxicity of Bi-based compounds was studied for years, there is a serious lack
      of information concerning their toxicity and effects in the nanoscale on human
      health and environment. Therefore, we aimed to investigate the toxic effects of
      Bi (III) oxide (Bi2O3) nanoparticles in liver (HepG2 hepatocarcinoma cell),
      kidney (NRK-52E kidney epithelial cell), intestine (Caco-2 colorectal
      adenocarcinoma cell), and lung (A549 lung carcinoma cell) cell cultures. Bi2O3
      nanoparticles (~149.1 nm) were easily taken by all cells and showed cyto- and
      genotoxic effects. It was observed that the main cell death pathways were
      apoptosis in HepG2 and NRK-52E cells and necrosis in A549 and Caco-2 cells
      exposed to Bi2O3 nanoparticles. Also, the glutathione (GSH), malondialdehyde
      (MDA), and 8-hydroxy deoxyguanine (8-OHdG) levels were significantly changed in
      HepG2, NRK-52E, and Caco-2 cells, except A549 cell. The present study is the
      first to evaluate the toxicity of Bi2O3 nanoparticles in mammalian cells. Bi2O3
      nanoparticles should be thoroughly assessed for their potential hazardous effects
      to human health and the results should be supported with in vivo studies to fully
      understand the mechanism of their toxicity.

PMID- 27870933
TI  - Bioremediation of hydrocarbon degradation in a petroleum-contaminated soil and
      microbial population and activity determination.
AB  - Bioremediation of hydrocarbon degradation in petroleum-polluted soil is carried
      out by various microorganisms. However, little information is available for the
      relationships between hydrocarbon degradation rates in petroleum-contaminated
      soil and microbial population and activity in laboratory assay. In a microcosm
      study, degradation rate and efficiency of total petroleum hydrocarbons (TPH),
      alkanes, and polycyclic aromatic hydrocarbons (PAH) in a petroleum-contaminated
      soil were determined using an infrared photometer oil content analyzer and a gas
      chromatography mass spectrometry (GC-MS). Also, the populations of TPH, alkane,
      and PAH degraders were enumerated by a modified most probable number (MPN)
      procedure, and the hydrocarbon degrading activities of these degraders were
      determined by the Biolog (MT2) MicroPlates assay. Results showed linear
      correlations between the TPH and alkane degradation rates and the population and
      activity increases of TPH and alkane degraders, but no correlation was observed
      between the PAH degradation rates and the PAH population and activity increases.
      Petroleum hydrocarbon degrading microbial population measured by MPN was
      significantly correlated with metabolic activity in the Biolog assay. The results
      suggest that the MPN procedure and the Biolog assay are efficient methods for
      assessing the rates of TPH and alkane, but not PAH, bioremediation in oil
      contaminated soil in laboratory.

PMID- 27870934
TI  - Remediation of hexavalent chromium spiked soil by using synthesized iron sulfide
      particles.
AB  - Carboxymethyl cellulose (CMC) stabilized microscale iron sulfide (FeS) particles
      were synthesized and applied to remediate hexavalent chromium (Cr(VI)) spiked
      soil. The effects of parameters including dosage of FeS particles, soil moisture,
      and natural organic matter (NOM) in soil were investigated with comparison to
      iron sulfate (FeSO4). The results show that the stabilized FeS particles can
      reduce Cr(VI) and immobilize Cr in soil quickly and efficiently. The soil
      moisture ranging from 40% to 70% and NOM in soil had no significant effects on
      Cr(VI) remediation by FeS particles. When molar ratio of FeS to Cr(VI) was 1.5:1,
      about 98% of Cr(VI) in soil was reduced by FeS particles in 3 d and Cr(VI)
      concentration decreased from 1407 mg kg-1 to 16 mg kg-1. The total Cr and Cr(VI)
      in Toxicity Characteristic Leaching Procedure (TCLP) leachate were reduced by
      98.4% and 99.4%, respectively. In FeS particles-treated soil, the exchangeable Cr
      fraction was mainly converted to Fe-Mn oxides bound fraction because of the
      precipitation of Cr(III)-Fe(III) hydroxides. The physiologically based extraction
      test (PBET) bioaccessibility of Cr was decreased from 58.67% to 6.98%. Compared
      to FeSO4, the high Cr(VI) removal and Cr immobilization efficiency makes prepared
      FeS particles a great potential in field application of Cr(VI) contaminated soil
      remediation.

PMID- 27870935
TI  - Effects of gamma radiation on cork wastewater: Antioxidant activity and toxicity.
AB  - A comprehensive assessment of the toxicity and antioxidant activity of cork
      boiling wastewater and the effects of gamma radiation on these parameters was
      performed. Antioxidant activity was evaluated using different methodologies as
      DPPH radical scavenging activity, reducing power and inhibition of beta-carotene
      bleaching. The results have shown that gamma radiation can induce an increase on
      the antioxidant activity of cork boiling wastewater. Toxicity tests were
      performed to access the potential added value of the irradiated wastewaters
      and/or minimization of the impact for discharge in the environment. Two different
      methods for toxicity evaluation were followed, bacterial growth inhibition test
      and cytotoxicity assay, in order to predict the behavior of different cells
      (prokaryotic and eukaryotic) in the presence of cork wastewater. Non-treated cork
      boiling wastewater seemed to be non-toxic for prokaryotic cells (Pseudomonas
      fluorescens and Bacillus subtilis) but toxic for eukaryotic cells (A549 human
      cells and RAW264.7 mouse cells). The gamma radiation treatment at doses of 100
      kGy appeared to increase the toxicity of cork compounds for all tested cells,
      which could be related to a toxic effect of radiolytic products of cork compounds
      in the wastewaters.

PMID- 27870937
TI  - Spinosad induces programmed cell death involves mitochondrial dysfunction and
      cytochrome C release in Spodoptera frugiperda Sf9 cells.
AB  - Spinosad, a reduced-risk insecticide, acts on the nicotinic acetylcholine
      receptors and the gamma-aminobutyric acid receptor in the nervous system of
      target insects. However, its mechanism of action in non-neural insect cells is
      unclear. This study aimed to evaluate mitochondrial functional changes associated
      with spinosad in Spodoptera frugiperda (Sf9) insect cells. Our results indicate
      that in Sf9 cells, spinosad induces programmed cell death and mitochondrial
      dysfunction through enhanced reactive oxygen species production, mitochondrial
      permeability transition pore (mPTP) opening, and mitochondrial membrane potential
      collapse, eventually leading to cytochrome C release and apoptosis. The
      cytochrome C release induced by spinosad treatment was partly inhibited by the
      mPTP inhibitors cyclosporin A and bongkrekic acid. Subsequently, we found that
      spinosad downregulated Bcl-2 expression and upregulated p53 and Bax expressions,
      activated caspase-9 and caspase-3, and triggered PARP cleavage in Sf9 cells.
      These findings suggested that spinosad-induced programmed cell death was
      modulated by mitochondrial dysfunction and cytochrome C release.

PMID- 27870936
TI  - Photochemical transformation of zearalenone in aqueous solutions under simulated
      solar irradiation: Kinetics and influence of water constituents.
AB  - The presence of estrogenic mycotoxins, such as zearalenone (ZEN), in surface
      waters is an emerging environmental issue. Little is known about its
      phototransformation behavior, which may influence its environmental fate. In this
      context, the phototransformation of ZEN was investigated in pure water, river
      water and estuarine water using simulated sunlight irradiation. Kinetic studies
      revealed that two concomitant processes contribute to the fate of ZEN under solar
      irradiation: photoisomerization and photodegradation. This phototransformation
      followed a pseudo-first order kinetics. ZEN degrades quickly in natural waters
      and slowly in deionized water, with half-lives (t1/2) of 28 +/- 4 min (estuarine
      water), 136 +/- 21 min (river water) and 1777 +/- 412 min (deionized water). The
      effects of different water constituents on the phototransformation of ZEN in
      aqueous solution have been assessed (NaCl, Ca2+, Mg2+, Fe3+, NO3- and oxalate
      ions, synthetic seawater, Fe(III)-oxalate and Mg(II)-oxalate complexes, humic
      acids, fulvic acids and XAD-4 fraction). In the presence of synthetic seawater
      salt (t1/2 = 18 +/- 5 min) and Fe(III)-oxalate complexes (t1/2 = 61 +/- 9 min),
      the transformation rate increased considerably in relation to other water
      constituents tested. The solution pH also had a considerable effect in the
      kinetics with maximum transformation rates occurring around pH 8.5. These results
      allow us to conclude that phototransformation by solar radiation can be an
      important degradation pathway of ZEN in natural waters.

PMID- 27870938
TI  - Evaluation of alpha-synuclein as a novel cerebrospinal fluid biomarker in
      different forms of prion diseases.
AB  - INTRODUCTION: Accurate diagnosis of prion diseases and discrimination from
      alternative dementias gain importance in the clinical routine, but partial
      overlap in cerebrospinal fluid (CSF) biomarkers impedes absolute discrimination
      in the differential diagnostic context. METHODS: We established the clinical
      parameters for prion disease diagnosis for the quantification of CSF alpha
      synuclein in patients with sporadic (n = 234) and genetic (n = 56) prion
      diseases, in cases with cognitive impairment/dementia or neurodegenerative
      disease (n = 278), and in the neurologic control group (n = 111). RESULTS: An
      optimal cutoff value of 680 pg/mL alpha-synuclein results in 94% sensitivity and
      96% specificity when diagnosing sporadic Creutzfeldt-Jakob disease (CJD). Genetic
      CJD cases showed increased CSF alpha-synuclein values. No increased alpha
      synuclein levels were detected in non-CJD cases with rapid progression course.
      DISCUSSION: Detection of alpha-synuclein in the CSF of patients with suspected
      CJD is a valuable diagnostic test reaching almost full discrimination from non
      prion disease cases. These data highlight the utility of CSF alpha-synuclein
      quantification in front of classical CSF biomarkers in clinical routine.

PMID- 27870939
TI  - Mixed neuropathologies and estimated rates of clinical progression in a large
      autopsy sample.
AB  - INTRODUCTION: Whether co-occurring neuropathologies interact or independently
      affect clinical disease progression is uncertain. We estimated rates of clinical
      progression and tested whether associations between clinical progression and
      Alzheimer's disease neuropathology (ADNP) were modified by co-occurring Lewy body
      disease (LBD) or vascular brain injury (VBI). METHODS: Linear mixed effects
      models evaluated longitudinal trends in the Clinical Dementia Rating Scale Sum of
      Boxes on 2046 autopsied participants seen at a U.S. Alzheimer's Disease Center.
      RESULTS: Annual clinical progression was slightly faster for ADNP + LBD compared
      with ADNP only (P = .06) and slightly slower for ADNP + VBI (P = .003).
      Differences in progression were less than expected if each neuropathology
      independently contributed to progression; ADNP interacted with LBD (P = .002) and
      VBI (P = .003). In secondary models, the effect of additional pathologies on
      clinical progression was greater in those with intermediate compared with high
      levels of ADNP. DISCUSSION: The impact of co-occurring pathologies on progression
      may depend on severity of ADNP.

PMID- 27870941
TI  - Nonverbal behaviors are associated with increased vagal activity in major
      depressive disorder: Implications for the polyvagal theory.
AB  - BACKGROUND: Major depressive disorder (MDD) is associated with impairments in
      nonverbal behaviors (NVBs) and vagal activity. The polyvagal theory proposes that
      vagal activity regulates heart rate and NVBs by modulating a common anatomically
      and neurophysiologically discrete social engagement system. However, the
      association between these putative endophenotypes has not yet been explored. We
      hypothesize that in MDD, NVBs indicating positive affects and social interest and
      those indicating negative feelings and social disinterest could be associated
      with different patterns of vagal activity. METHODS: For this cross-sectional
      study we recruited 50 antidepressant-free participants with moderate-to-severe
      MDD. Vagal activity was indexed by heart rate variability (HRV) measures, and
      positive and negative nonverbal behaviors (NVBs) by a validated ethogram.
      Associations between NVBs and HRV were explored by bivariate analyses and
      multivariable models were adjusted by age, gender, depression severity, and self
      reported positive and negative affects. RESULTS: HRV measures indicative of
      higher vagal activity were positively correlated with positive NVBs exhibited
      during the clinical interview. Conversely, NVBs related to negative affects, low
      energy and social disinterest were not associated with HRV. LIMITATIONS: Absence
      of a control group. CONCLUSIONS: The findings highlight that the examined
      depression endophenotypes (nonverbal behaviors and vagal activity) are related,
      shedding light on MDD pathophysiology in the context of the polyvagal theory.

PMID- 27870940
TI  - Blood-based biomarkers in Alzheimer disease: Current state of the science and a
      novel collaborative paradigm for advancing from discovery to clinic.
AB  - The last decade has seen a substantial increase in research focused on the
      identification of blood-based biomarkers that have utility in Alzheimer's disease
      (AD). Blood-based biomarkers have significant advantages of being time- and cost
      efficient as well as reduced invasiveness and increased patient acceptance.
      Despite these advantages and increased research efforts, the field has been
      hampered by lack of reproducibility and an unclear path for moving basic
      discovery toward clinical utilization. Here we reviewed the recent literature on
      blood-based biomarkers in AD to provide a current state of the art. In addition,
      a collaborative model is proposed that leverages academic and industry strengths
      to facilitate the field in moving past discovery only work and toward clinical
      use. Key resources are provided. This new public-private partnership model is
      intended to circumvent the traditional handoff model and provide a clear and
      useful paradigm for the advancement of biomarker science in AD and other
      neurodegenerative diseases.

PMID- 27870943
TI  - Longitudinal monitoring of heartbeat dynamics predicts mood changes in bipolar
      patients: A pilot study.
AB  - OBJECTIVES: Recent research indicates that Heart Rate Variability (HRV) is
      affected in Bipolar Disorders (BD) patients. To determine whether such
      alterations are a mere expression of the current mood state or rather contain
      longitudinal information on BD course, we examined the potential influence of
      states adjacent in time upon HRV features measured in a target mood state.
      METHODS: Longitudinal evaluation of HRV was obtained in eight BD patients by
      using a wearable monitoring system developed within the PSYCHE project. We
      extracted time-domain, frequency-domain and non-linear HRV-features and trained a
      Support Vector Machine (SVM) to classify HRV-features according to mood state. To
      evaluate the influence of adjacent mood states, we trained SVM with different HRV
      feature sets: 1) belonging to each mood state considered alone; 2) belonging to
      each mood state and normalized using information from the preceding mood state;
      3) belonging to each mood state and normalized using information from the
      preceding and subsequent mood states; 4) belonging to each mood state and
      normalized using information from two randomly chosen states. RESULTS: SVM
      classification accuracy within a target state was significantly greater when HRV
      features from the previous and subsequent mood states were considered.
      CONCLUSIONS: Although preliminary and in need of replications our results suggest
      for the first time that psychophysiological states in BD contain information
      related to the subsequent ones. Such characteristic may be used to improve
      clinical management and to develop algorithms to predict clinical course and mood
      switches in individual patients.

PMID- 27870942
TI  - Altered time course of amygdala activation during speech anticipation in social
      anxiety disorder.
AB  - BACKGROUND: Exaggerated anticipatory anxiety is common in social anxiety disorder
      (SAD). Neuroimaging studies have revealed altered neural activity in response to
      social stimuli in SAD, but fewer studies have examined neural activity during
      anticipation of feared social stimuli in SAD. The current study examined the time
      course and magnitude of activity in threat processing brain regions during speech
      anticipation in socially anxious individuals and healthy controls (HC). METHOD:
      Participants (SAD n=58; HC n=16) underwent functional magnetic resonance imaging
      (fMRI) during which they completed a 90s control anticipation task and 90s speech
      anticipation task. Repeated measures multi-level modeling analyses were used to
      examine group differences in time course activity during speech vs. control
      anticipation for regions of interest, including bilateral amygdala, insula,
      ventral striatum, and dorsal anterior cingulate cortex. RESULTS: The time course
      of amygdala activity was more prolonged and less variable throughout speech
      anticipation in SAD participants compared to HCs, whereas the overall magnitude
      of amygdala response did not differ between groups. Magnitude and time course of
      activity was largely similar between groups across other regions of interest.
      LIMITATIONS: Analyses were restricted to regions of interest and task order was
      the same across participants due to the nature of deception instructions.
      CONCLUSIONS: Sustained amygdala time course during anticipation may uniquely
      reflect heightened detection of threat or deficits in emotion regulation in
      socially anxious individuals. Findings highlight the importance of examining
      temporal dynamics of amygdala responding.

PMID- 27870945
TI  - Erythropoietin administration is associated with improved T-cell properties in
      patients with myelodysplastic syndromes.
AB  - The immune system is impaired in myelodysplastic syndromes (MDS) and plays a role
      in the pathogenesis of the disease. Here we show effects of recombinant human
      erythropoietin (rHuEPO) on T cell (CD4+, CD8+ and CD4+CD25+) number and function
      in MDS patients. Healthy (20 subjects), MDS patients without rHuEPO treatment
      ('MDS', 13), and MDS patients treated with rHuEPO ('MDS+EPO', 17) were examined.
      CD4+ and CD8+ T cell numbers were reduced and increased respectively in MDS
      compared to healthy subjects. EPO treatment normalized these levels. CD4+CD25+
      cell numbers, lower in MDS, were normalized in MDS+EPO. In vitro activation of
      CD4+ and CD8+ cells with phytohemagglutinin as measured by CD69 expression,
      demonstrated a 7.2 fold increase in CD4+ activation vs 13.6 fold for MDS and
      MDS+EPO respectively (p=0.004); and 10.2 fold (MDS) vs 18.6 fold (MDS+EPO,
      p<0.003) for CD8+ T cells. Expression of the co-stimulatory marker CD28,
      decreased in CD4+ and CD8+ T cells in MDS, was normalized in MDS+EPO CD4+ T
      cells. Subgroup analysis of milder disease (WHO RA and RARS) and more advanced
      disease revealed no difference in CD4+ and CD8+ T cell numbers. However, the
      activation of these cells in the RA/RARS subgroup was impaired in EPO-untreated
      and enhanced in EPO-treated MDS patients. Our data suggest that EPO treatment
      improves immune abnormalities in MDS and may depend on disease severity.

PMID- 27870946
TI  - Conserved hierarchical gain of chromosome 4 is an independent prognostic factor
      in high hyperdiploid pediatric acute lymphoblastic leukemia.
AB  - BACKGROUND: High hyperdiploid (HeH) pre-B pediatric acute lymphoblastic leukemia
      (B-pALL) is known to be heterogeneous by prognosis, but the stratification
      principals according to conventional cytogenetic analysis (CCA) are equivocal.
      PROCEDURE: Untreated bone marrow samples of 214 B-pALL patients were previously
      classified according to the modal numbers (iMN8) based on the gains of the
      chromosomes 4, 6, 10, 14, 17, 18, 21, and X as revealed by consecutive and
      correlated 2*4 color interphase fluorescence in situ hybridization, and at least
      five years of follow up data were analyzed. RESULTS: Data from 48 of the 53 HeH
      (iMN8>50) B-pALL patients indicated that among the age, gender, WBC, and iMN8
      parameters, only the last was significantly associated with overall survival
      (pOS), which allowed the cases to be classified as iMN8 51-54 (75%) and iMN8 >=
      55 (95%). Among the specific chromosomal gains of +4, +4/+6, +4/+17 and +4/+18,
      the first exhibited the most significance in terms of beneficial outcomes. The
      better prognostic group according to the iMN8 was associated with a significantly
      reduced complexity of the subclonal landscape. However, iMN8 did not prove to be
      an independent variable but was instead overridden by isolated trisomy of
      chromosome 4. CONCLUSIONS: These data indicate that the better outcomes in the
      HeH B-pALL group arose from the gain of a specific chromosome that always ranks
      at the same position in the sequential acquisition of the affected chromosomes.

PMID- 27870944
TI  - Application of Single-Molecule Amplification and Resequencing Technology for
      Broad Surveillance of Plasma Mutations in Patients with Advanced Lung
      Adenocarcinoma.
AB  - Liquid biopsy to access the circulating tumor DNA is a promising surrogate for
      invasive tumor genotyping. We designed a multiplex assay based on circulating
      single-molecule amplification and resequencing technology (cSMART) to
      simultaneously detect and quantitate hot spot EGFR, KRAS, BRAF, ERBB2, and ALK
      plasma DNA variants in 103 patients with advanced lung adenocarcinoma. In
      validation studies using an analytical mutation standard, the sensitivity of the
      assay for EGFR mutation detection was at least 0.1% and specificity was 100%. The
      diagnostic detection sensitivity was one mutant molecule per 2 mL of plasma. The
      most frequently detected plasma mutations were EGFR variants L858R (21.4%), exon
      19 deletions (19.4%), T790M (9.7%), and KRAS G12X variants (9.7%). Rarer were
      BRAF V600X (1.95%) and ERBB2 exon 20 (0.97%) variants. In single samples, four
      novel EGFR exon 19 deletions, one KIF5B-ALK, and two EML4-ALK variants were also
      detected. From comparisons of 103 matched plasma and tumor specimen genotypes, 75
      (72.8%) were concordant, 9 (8.8%) were partially concordant, and 19 (18.4%) were
      discordant. Overall, the combined positive and negative concordance rate for
      detection of each oncogenic variant exceeded 90%. On the basis of these findings,
      we propose that cSMART displays the diagnostic hallmarks of a comprehensive
      plasma genotyping assay, with potential application for precisely monitoring
      changes in plasma mutation levels in response to targeted drug therapy.

PMID- 27870947
TI  - Subcellular localization of the FLT3-ITD oncogene plays a significant role in the
      production of NOX- and p22phox-derived reactive oxygen species in acute myeloid
      leukemia.
AB  - Internal tandem duplication of the juxtamembrane domain of FMS-like tyrosine
      kinase 3 (FLT3-ITD) receptor is the most prevalent FLT3 mutation accounting for
      20% of acute myeloid leukemia (AML) patients. FLT3-ITD mutation results in ligand
      independent constitutive activation of the receptor at the plasma membrane and
      'impaired trafficking' of the receptor in compartments of the endomembrane
      system, such as the endoplasmic reticulum (ER). FLT3-ITD expressing cells have
      been shown to generate increased levels of reactive oxygen species (ROS), in
      particular NADPH oxidase (NOX)-generated ROS which act as pro-survival signals.
      The purpose of this study is to investigate FLT3-ITD production of ROS at the
      plasma membrane and ER in the FLT3-ITD expressing AML cell line MV4-11. Receptor
      trafficking inhibitors; Tunicamycin and Brefeldin A induce ER retention of FLT3
      ITD, resulting in a decrease in protein expression of NOX4 and its partner
      protein p22phox, thus demonstrating the critical importance of FLT3-ITD
      localization for the generation of pro-survival ROS. NOX-generated ROS contribute
      to total endogenous hydrogen peroxide (H2O2) in AML as quantified by flow
      cytometry using the cell-permeable H2O2-probe Peroxy Orange 1 (PO1). We found
      that PI3K/AKT signaling only occurs when FLT3-ITD is expressed at the plasma
      membrane and is required for the production of NOX-generated ROS. ER retention of
      FLT3-ITD resulted in NOX4 deglycosylation and p22phox protein degradation.

PMID- 27870948
TI  - HbA1c increase is associated with higher coronary and peripheral atherosclerotic
      burden in non diabetic patients.
AB  - BACKGROUND AND AIMS: Prediabetes is associated with an increased risk of
      developing diabetes and cardiovascular disease. Our objective was to examine the
      cardiovascular (CV) risk profile of non-diabetic patients with and without
      prediabetes according to HbA1c, using macroangiopathic imaging biomarkers.
      METHODS: Our population consisted of 272 non diabetic patients aged between 40
      and 70 years, with a normal fasting plasma glucose (FPG <5.6 mmol/L) and at least
      1 CV risk factor. Exclusion criteria were prior history of CV disease or clinical
      evidence of advanced renal disease. Prediabetes was defined as an HbA1c value of
      5.7-6.4%. Coronary artery calcium (CAC) score as well as mean common carotid
      intima media thickness (IMT) and plaque presence were assessed using consensus
      criteria. RESULTS: CAC score was higher in the prediabetes group compared to non
      prediabetic subjects (131.7 +/- 295.6 vs. 62.4 +/- 178.8 AU, p < 0.001).
      Prediabetic subjects had higher mean IMT than non-exposed subjects (0.77 +/- 0.14
      vs. 0.61 +/- 0.15 mm, p < 0.001). The proportion of prediabetic patients with CAC
      = 0 was significantly lower compared to non-exposed subjects (35% vs. 63%, p <
      0.01). In contrast, the proportion of patients with a CAC >400 was significantly
      higher in the prediabetes group (10% vs. 3%, p < 0.05). Moreover, carotid plaques
      were significantly more present in patients with prediabetes than in the
      normoglycemic subjects (p < 0.01). In a multiple linear regression, IMT was
      associated with HbA1c continuous levels (p < 0.001). In addition, logistic
      regression showed that higher HbA1c levels were associated with CAC and carotid
      plaques presence (p for trend for all < 0.001). CONCLUSIONS: Among patients with
      normal fasting glucose, HbA1c increase is associated with higher coronary and
      peripheral atherosclerotic burden in non-diabetic patients.

PMID- 27870950
TI  - Impact of particle-laden drops: Particle distribution on the substrate.
AB  - The splat morphology after the impact of suspension drops on hydrophilic (glass)
      and hydrophobic (polycarbonate) substrates was investigated. The suspensions were
      mixtures of water and spherical hydrophobic particles with diameter of 200MUm or
      500MUm. The impact was studied by side, bottom and angled view images. At
      Reynolds and Weber numbers in the range 150?We?750 and 7100?Re?16,400, the
      particles distributed in a monolayer on the hydrophilic substrates. It was found
      that the 200MUm particles self-arranged as rings or disks on the hydrophilic
      substrates. On hydrophobic substrates, many particles were at the air-water
      interface and 200MUm formed a crown-like structure. The current study for impact
      of particle-laden drops shows that the morphology of splats depends on the
      substrate wettability, the particle size and impact velocity. We developed
      correlations for the inner and outer diameter of the particle distribution on the
      hydrophilic substrates, and for the crown height on hydrophobic substrates. The
      proposed correlations capture the character of the particle distributions after
      drop impact that depends on particle volume fraction, the wettability of both
      particles and the substrate, and the dimensionless numbers such as Reynolds and
      Weber.

PMID- 27870949
TI  - Green synthesis of Pd nanoparticles at Apricot kernel shell substrate using
      Salvia hydrangea extract: Catalytic activity for reduction of organic dyes.
AB  - For the first time the extract of the plant of Salvia hydrangea was used to green
      synthesis of Pd nanoparticles (NPs) supported on Apricot kernel shell as an
      environmentally benign support. The Pd NPs/Apricot kernel shell as an effective
      catalyst was prepared through reduction of Pd2+ ions using Salvia hydrangea
      extract as the reducing and capping agent and Pd NPs immobilization on Apricot
      kernel shell surface in the absence of any stabilizer or surfactant. According to
      FT-IR analysis, the hydroxyl groups of phenolics in Salvia hydrangea extract as
      bioreductant agents are directly responsible for the reduction of Pd2+ ions and
      formation of Pd NPs. The as-prepared catalyst was characterized by Fourier
      transform infrared (FT-IR) and UV-Vis spectroscopy, field emission scanning
      electron microscopy (FESEM) equipped with an energy dispersive X-ray spectroscopy
      (EDS), Elemental mapping, X-ray diffraction analysis (XRD) and transmittance
      electron microscopy (TEM). The synthesized catalyst was used in the reduction of
      4-nitrophenol (4-NP), Methyl Orange (MO), Methylene Blue (MB), Rhodamine B (RhB),
      and Congo Red (CR) at room temperature. The Pd NPs/Apricot kernel shell showed
      excellent catalytic activity in the reduction of these organic dyes. In addition,
      it was found that Pd NPs/Apricot kernel shell can be recovered and reused several
      times without significant loss of catalytic activity.

PMID- 27870951
TI  - Simultaneous determination of trace Cd(II), Pb(II) and Cu(II) by differential
      pulse anodic stripping voltammetry using a reduced graphene oxide-chitosan/poly-l
      lysine nanocomposite modified glassy carbon electrode.
AB  - The reduced graphene oxide (RGO) and Chitosan (CS) hybrid matrix RGO-CS were
      coated onto the glassy carbon electrode (GCE) surface, then, poly-l-lysine films
      (PLL) were prepared by electropolymerization with cyclic voltammetry (CV) method
      to prepare RGO-CS/PLL modified glassy carbon electrode (RGO-CS/PLL/GCE) for the
      simultaneous electrochemical determination of heavy metal ions Cd(II), Pb(II) and
      Cu(II). Combining the advantageous features of RGO and CS, RGO and CS are used
      together because the positively charged CS can interact with the negatively
      changed RGO to prevent their aggregation. Furthermore, CS has many amino groups
      along its macromolecular chains and possessed strongly reactive with metal ions.
      Moreover, PLL modified electrodes have good stability, excellent permselectivity,
      more active sites and strong adherence to electrode surface, which enhanced
      electrocatalytic activity. The RGO-CS/PLL/GCE was characterized voltammetrically
      using redox couples (Fe(CN)63-/4-), complemented with electrochemical impedance
      spectroscopy (EIS). Differential pulse anodic stripping voltammetry (DPASV) has
      been used for the detection of Cd(II), Pb(II) and Cu(II). The detection limit of
      RGO-CS/PLL/GCE toward Cd(II), Pb(II) and Cu(II) is 0.01MUgL-1, 0.02MUgL-1 and
      0.02MUgL-1, respectively. The electrochemical parameters that exert influence on
      deposition and stripping of metal ions, such as supporting electrolytes, pH
      value, deposition potential, and deposition time, were carefully studied.

PMID- 27870952
TI  - Hexadecyltrimethylammonium bromide (CTA-Br) and 1-butyl-3-methylimidazolium
      tetrafluoroborate (bmim-BF4) in aqueous solution: An ephemeral binary system.
AB  - HYPOTHESIS: Mixtures of the cationic surfactant hexadecyltrimethylammonium
      bromide (CTA-Br) and the ionic liquid 1-butyl-3-methylimidazolium
      tetrafluoroborate (bmim-BF4) in aqueous solutions are expected to behave as
      typical binary cationic surfactant system taking into account the surface
      activity displayed by the ionic liquid, instead of considering the IL as a water
      cosolvent. EXPERIMENTS: Surface tension and conductivity measurements have been
      conducted as a function of the total concentration of the mixtures at different
      surfactant mole fraction (alphaCTA-Br) to investigate the surface active
      properties. FINDINGS: Turbidity immediately appearing when the compounds are
      mixed in water suggests the spontaneous formation of the low soluble compound
      hexadecyltrimethylammonium tetrafluoroborate (CTA-BF4), together with the salt
      formed by the respective counterions bmim+and Br- in solution. For alphaCTA
      Br?0.5, furthermore of the mentioned compounds, the spare bmim-BF4 (for alphaCTA
      Br<0.5) or CTA-Br (for alphaCTA-Br>0.5), are also present in the aqueous
      solution. Systems containing excess of bmim-BF4 show a low critical aggregate
      concentration (cac), but an unexpected high surface tension at cac (gammacac~53
      56mN/m), as pure CTA-BF4. For systems containing excess of CTA-Br, cac increases
      but gammacac decreases up to 36mN/m. Mixtures of pure CTA-BF4 and bmim-BF4 or CTA
      Br behave as typical binary surfactant systems.

PMID- 27870953
TI  - Comparative NO2-sensing in cobalt and metal-free porphyrin nanotubes.
AB  - In the present study, the nanotubes of 5-(4-hydroxyphenyl)-10, 15, 20-tri(4
      chlorophenyl) porphyrin (p-HTClPP) (1) and 5-(4-hydroxyphenyl)-10, 15, 20-tri(4
      chlorophenyl) porphyrin cobalt (p-HTClPPCo) (2) were successfully prepared by
      using anodize alumina oxide (AAO) template method. The p-HTClPP and p-HTClPPCo
      nanotubes have been confirmed by scanning electron microscopy (SEM), transmission
      electron microscopy (TEM), electronic absorption spectra, fluorescence
      spectroscopy, fourier transform infrared spectroscopy (FT-IR), low-angle X-ray
      diffraction (XRD) and energy dispersive spectroscopy (EDS) techniques. Both p
      HTClPPCo and p-HTClPP nanotubes showed excellent sensitivity, reproducibility and
      selectivity toward NO2. Especially the prepared sensor of p-HTClPPCo nanotubes
      exhibited faster response/recovery characteristics and lower detection limit of
      NO2 (up to 500ppb) than that of p-HTClPP nanotubes, which pave a new avenue in
      the gas sensitive field.

PMID- 27870956
TI  - Mixed-matrix membranes incorporated with porous shape-persistent organic cages
      for gas separation.
AB  - There has been much recent interest in the use of porous materials derived from
      self-assembling, shape-persistent organic cages due to their solubility and easy
      post-synthetic modification. Herein we report the preparation of novel mixed
      matrix membranes (MMMs) employing the porous organic cage Noria and its
      derivatives Noria-Boc and Noria-COtBu as the fillers, and a fluorine containing
      polyimide, 6FDA-DAM, as the polymeric matrix. The physical structures and
      properties of Noria and its derivatives were measured and investigated. Noria
      with substituents of Boc (cleaved by thermal treatment during the process of
      membrane fabrication) and COtBu groups tend to show much better compatibility
      with polyimide than Noria itself, resulting in homogeneous dispersion of
      nanoaggregates and fine adhesion between the two phases in the derived Noria/6FDA
      DAM and Noria-COtBu/6FDA-DAM MMMs. Gas permeation tests revealed that Noria and
      Noria-COtBu nanoparticles have different effect on gas separation performance of
      MMMs. The introduction of Noria into 6FDA-DAM tends to enhance CO2/CH4
      selectivity and thus improve its gas separation properties, though a decrease in
      the observed permeability could be observed. In contrast, the introduction of
      Noria-COtBu with higher surface area and larger pores tends to increase the free
      volume and gas permeability of MMMs. These results show that both the morphology
      and the gas separation properties of MMMs could be tuned by tailoring the
      structures of porous organic cages.

PMID- 27870954
TI  - Synthesis and characterization of O-acylated-omega-hydroxy fatty acids as skin
      protecting barrier lipids.
AB  - A series of O-acylated-omega-hydroxy fatty acids (Acyl acids) of up to 34 carbons
      were synthesized and characterized through DSC, FTIR and Langmuir isotherm
      measurements to identify potential replacements to petrolatum, a highly used
      occlusive technology that if unrefined, it can potentially be classified as
      carcinogenic. Fourier transform infrared spectroscopy studies demonstrated that
      long acyl acids engender orthorhombic packing; packing behavior that is
      predominant in the lipid matrix of healthy stratum corneum, the outmost layer of
      the skin. In addition, Differential Scanning Calorimetry (DSC) and Langmuir
      isotherm studies suggested that the length of the hydrocarbon chain and the
      position of the ester bond influence the molecular organization of the acyl
      acids. For instance, 16-(tetradecanoyloxy)hexadecanoic acid (30 carbons)
      displayed a higher melting point (mp=68 degrees C) than 10-(stearoyloxy)decanoic
      acid (28 carbons; mp=63 degrees C) and 10-(tetradecanoyloxy)decanoic acid (24
      carbons; mp=55 degrees C) according to DSC. Moreover, Langmuir isotherm studies
      showed that mixtures of acyl acid with distearoylphosphatidylcholine improved
      packing behavior. Finally, Water Vapor Transmission Rate (WVTR) measurements
      showed that the compounds in fact decrease WVTR compared to untreated control
      (P<0.001) which demonstrates the potential of these ingredients as occlusive
      technologies to combat skin barrier diseases.

PMID- 27870955
TI  - Ultrafast self-assembly of silver nanostructures on carbon-coated copper grids
      for surface-enhanced Raman scattering detection of trace melamine.
AB  - Structurally well-defined assemblies of silver nanoparticles, including the
      dendritic nano-flowers (NFs), planar nano-spheres (NSs) and nano-dendrites (NDs)
      were obtained by a surfactant-free and ultrafast (~15min) self-assembly process
      on as-purchased carbon-coated copper TEM grids. The silver nano-assemblies,
      especially the NFs modified TEM grids, when serving as surface-enhanced Raman
      spectroscopy (SERS) substrates for detecting melamine molecules, demonstrated a
      long-lived limit of detection (LOD) of as low as 10-11M, suggesting the potential
      of these silver-assemblies modified carbon-coated copper grids as novel potable
      and cost-effective SERS substrates for trace detection toward various food
      contaminants like melamine.

PMID- 27870957
TI  - Influence of TiO2 hollow sphere size on its photo-reduction activity for toxic
      Cr(VI) removal.
AB  - After polystyrene@titanium dioxide (PS@TiO2) composite with different size was
      calcined at designated temperature, TiO2 hollow sphere with controllable size was
      obtained for high efficient photo-reduction of Cr(VI). The feature of the TiO2
      hollow sphere was investigated by SEM, TEM, XRD, UV-Vis, and photoluminescence.
      The photo-reduction of Cr(VI) were measured for the performance assessment of the
      TiO2 hollow sphere, Cr(VI) was used as an electron acceptor. After irradiation
      for 2h, the photo-reduction rate of Cr(VI) (pH=2.82) for TiO2(450nm) was 96%,
      which exhibited an increase of 5% and 8% compared with TiO2(370nm) and
      TiO2(600nm). The absorption edges of TiO2 hollow sphere (450nm) was largest with
      the increasing of hollow sphere size from 370 to 600nm. The optimal hollow sphere
      size of TiO2 was 450nm for the photo-reduction of Cr(VI), because the light
      harvesting efficiency (the best of absorption edge) and photo-generated electron
      hole separation rate (the best of photo-reduction rate) of TiO2 hollow sphere
      were controlled by its hollow sphere size. In addition, we find that the behavior
      of the hydrogen production was inhibited by the coexistence Cr(VI) solution. This
      study can improve our understanding of the mechanism for the activity enhancement
      by the optimal hollow sphere size of TiO2.

PMID- 27870958
TI  - Enhanced photocatalytic properties of alpha-SnWO4 nanosheets modified by Ag
      nanoparticles.
AB  - Decoration of silver nanoparticles (Ag-NPs) on surface of alpha-SnWO4 nanosheets
      has been achieved by a microwave-assisted deposition method. The as-synthesized
      products are structurally characterized by X-ray diffraction (XRD) and
      transmission electron microscopy (TEM). The results illustrate that Ag-NPs are
      evenly anchored onto alpha-SnWO4 surface to form close heterojunction and the
      amount of Ag nanoparticles grown on alpha-SnWO4 nanosheets can be well controlled
      by tuning Ag+ concentration. The photocatalytic properties of Ag-NPs/alpha-SnWO4
      composites are evaluated by degrading methyl orange (MO) under visible-light
      irradiation. Ag-NPs/alpha-SnWO4 composites exhibit better photocatalytic
      properties than that of pure alpha-SnWO4, and Ag-NPs/alpha-SnWO4 (5mol% Ag)
      presents the best photocatalytic activity, whose photodegradation efficiency of
      MO is about 97% within 70min. In addition, the obtained samples demonstrate good
      recyclability. The enhanced photocatalytic properties was attributed to
      synergistic effect between Ag-NPs and alpha-SnWO4 nanosheets, which can increase
      absorption of visible light enabled by surface plasma resonance (SPR) of Ag-NPs
      and facilitate the separation of photogenerated electron-hole pairs.

PMID- 27870959
TI  - High performance flexible pH sensor based on polyaniline nanopillar array
      electrode.
AB  - Flexible pH sensor technologies have attracted a great deal of attention in many
      applications, such as, wearable health care devices and monitors for chemical and
      biological processes. Here, we fabricated flexible and thin pH sensors using a
      two electrode configuration comprised of a polyaniline nanopillar (PAN) array
      working electrode and an Ag/AgCl reference electrode. In order to provide
      nanostructure, soft lithography using a polymeric blend was employed to create a
      flexible nanopillar backbone film. Polyaniline-sensing materials were deposited
      on a patterned-nanopillar array by electrochemical deposition. The pH sensors
      produced exhibited a near-Nernstian response (~60.3mV/pH), which was maintained
      in a bent state. In addition, pH sensors showed other excellent sensor
      performances in terms of response time, reversibility, repeatability,
      selectivity, and stability.

PMID- 27870960
TI  - Towards an accurate estimation of the isosteric heat of adsorption - A
      correlation with the potential theory.
AB  - Accurate estimation of the isosteric heat of adsorption is mandatory for a good
      modeling of adsorption processes. In this paper a thermodynamic formalism on
      adsorbed phase volume which is a function of adsorption pressure and temperature
      has been proposed for the precise estimation of the isosteric heat of adsorption.
      The estimated isosteric heat of adsorption using the new correlation has been
      compared with measured values of prudently selected several adsorbent-refrigerant
      pairs from open literature. Results showed that the proposed isosteric heat of
      adsorption correlation fits the experimentally measured values better than the
      Clausius-Clapeyron equation.

PMID- 27870961
TI  - Design and construction of multifunctional hyperbranched polymers coated
      magnetite nanoparticles for both targeting magnetic resonance imaging and cancer
      therapy.
AB  - Magnetic drug targeting is a drug delivery strategy that can be used to improve
      the therapeutic efficiency on tumor cells and reduce the side effects on normal
      cells and tissues. The aim in this study is designing a novel multifunctional
      drug delivery system based on superparamagnetic nanoparticles for cancer therapy.
      Magnetic nanoparticles were synthesized by coprecipitation of iron oxide followed
      by coating with poly citric acid (PCA) dendritic macromolecules via bulk
      polymerization strategy. It was further surface-functionalized with poly(ethylene
      glycol) (PEG) and then to achieve tumor cell targeting property, folic acid was
      further incorporated to the surface of prepared carriers via a facile coupling
      reaction between the hydroxyl end group of the PEG and the carboxyl group of
      folic acid. The so prepared nanocarriers (Fe3O4@PCA-PEG-FA) were characterized by
      X-ray diffraction, TEM, TGA, FT-IR, DLS and VSM techniques. The room temperature
      VSM measurements showed that magnetic particles were superparamagnetic.
      Transmission electron microscopy and dynamic light scattering were also performed
      which revealed that size of nanocarriers was lying in the range of 10-49nm.
      Quercetin loading and release profiles of prepared nanocarriers showed that up to
      83% of loaded drug was released in 250h. Fluorescent microscopy showed that the
      cellular uptake by folate receptor-overexpressing HeLa cells of the quercetin
      loaded Fe3O4@PCA-PEG-FA nanoparticles was higher than that of non-folate
      conjugated nanoparticles. Thus, folate conjugation significantly increased
      nanoparticle cytotoxicity. Also, T2-weighted MRI images of Fe3O4@PCA-PEG-FA
      nanoparticles showed that the magnetic resonance signal is enhanced significantly
      with increasing nanoparticle concentration in water and they also served as MRI
      contrast agents with relaxivities of 3.4mM-1s-1 (r1) and 99.8mM-1s-1 (r2). The
      results indicate that this multifunctional nanocarrier is a significant
      breakthrough in developing a drug delivery vehicle that combines drug targeting
      as well as sensing and therapy at the same time.

PMID- 27870963
TI  - Ultra-hydrophobic sticky polymer surfaces formed by water-induced surface
      deformation.
AB  - Surface properties of poly(oxyethylene)s with alkyl thioether side chains (CH3
      nTE; n=carbon atoms in the side chain) were investigated. CH3-nTEs having shorter
      side chains (n=6, 8, 10) did not have ordered structures, while those with longer
      chains (n=12, 14) showed well-ordered, lamellar structures with side chain
      crystalline domains. Accordingly, CH3-12TE and CH3-14TE film surfaces were much
      more enriched with hydrophobic alkyl side chains than CH3-8TE and CH3-10TE
      surfaces. However, CH3-12TE and CH3-14TE films had smaller water contact angles
      (~114 degrees ) than CH3-8TE and CH3-10TE films (>130 degrees ). This unexpected
      behavior is ascribed to the formation of very rough CH3-8TE and CH3-10TE film
      surfaces (Rrms>100nm) on contact with water. The CH3-10TE/poly(methyl
      methacrylate) (PMMA) surfaces also showed high water contact angles (>125 degrees
      ), even with low CH3-10TE content (30wt%), because the CH3-10TE moiety roughened
      the surfaces. Furthermore, ultra-hydrophobic sticky behavior was observed for CH3
      nTEs (n=8, 10) and CH3-10TE/PMMA surfaces.

PMID- 27870962
TI  - Pore volume and distribution regulation of highly nanoporous titanium dioxide
      nanofibers and their photovoltaic properties.
AB  - By combining the initial solvent volatilization and ultimate calcination to form
      highly nanoporous polystyrene/titanium dioxide (PS/TiO2) composite nanofibrous
      mats were fabricated via electrospinning, then the PS was removed afterwards by
      calcination, and finally porous TiO2 nanofibers were formed successfully. The
      porous structure of the nanofibers was characterized by field emission scanning
      electron microscopy and Brunauer-Emmett-Teller measurements, which indicated that
      the size and the diameter of the pore and the ratio of the surface area to the
      volume of the mats were regulated by adjusting the weight ratios of
      tetrahydrofuran and N,N-dimethylformamide in the binary solvent mixtures. X-ray
      photoelectron spectroscopy and Raman analysis confirmed that the addition of TiO2
      into the fibers was successful and that PS decomposed completely from fibers
      after calcination at 500 degrees C. The photovoltaic measurements showed that the
      obtained TiO2 nanofibers were ideal candidates for the fabrication of the
      photoanodes on the dye-sensitized solar cells.

PMID- 27870964
TI  - High performance electrochemical pseudocapacitors from ionic liquid assisted
      electrochemically synthesized p-type conductive polymer.
AB  - In this paper firstly, 1-methyl-3-methylimidazolium bromide (MB) as a new high
      efficient ionic liquid was synthesized using chemical approach and then
      fabricated POAP/MB films by electro-polymerization of POAP in the presence of MB
      to serve as the active electrode for electrochemical supercapacitor. Theoretical
      study (AIM) and electrochemical analysis have been used for characterization of
      ionic liquid and POAP/MB composite film. Different electrochemical methods
      including galvanostatic charge-discharge experiments, cyclic voltammetry and
      electrochemical impedance spectroscopy are carried out in order to investigate
      the performance of the system. This work introduces new most efficient materials
      for electrochemical redox capacitors with advantages including ease synthesis,
      high active surface area and stability in an aqueous electrolyte.

PMID- 27870965
TI  - A biocompatible and novelly-defined Al-HAP adsorption membrane for highly
      effective removal of fluoride from drinking water.
AB  - A biocompatible and novelly-defined adsorption membrane for rapid removal of
      fluoride was prepared. Both adsorption and membrane techniques were used in this
      research. Al(OH)3 nanoparticles modified hydroxyapatite (Al-HAP) nanowires were
      developed and made into Al-HAP membrane. The adsorption data of Al-HAP adsorbent
      could be well described by Freundlich isotherm model while the adsorption kinetic
      followed pseudo-second-order model. The maximum of adsorption capacity was
      93.84mg/g when the fluoride concentration was 200mg/L. The adsorption mechanism
      was anion exchanges and electrostatic interactions. The contribution rates of HAP
      nanowires and Al(OH)3 nanoparticles in fluoride removal were 36.70% and 63.30%,
      respectively. The fixed-bed column test demonstrate that the Al-HAP was
      biocompatible and in a good stability during the process of water treatment. The
      fluoride removal abilities of Al-HAP membrane with 0.3mm thickness could reach
      1568L/m2 when fluoride concentrations were 5mg/L. This study indicated that the
      Al-HAP membrane could be developed into a very viable technology for highly
      effective removal of fluoride from drinking water.

PMID- 27870966
TI  - Biochemical effects of fipronil and its metabolites on lipid peroxidation and
      enzymatic antioxidant defense in tadpoles (Eupemphix nattereri: Leiuperidae).
AB  - Amphibians are very sensitive to environmental change and pollution because they
      have both aquatic and terrestrial life cycle stages and high skin permeability.
      Particularly during the larval stages, when these animals are restricted to
      small, transient ponds, exposure to high concentrations of pesticides is
      inevitable in agricultural areas. Given that pesticide application increases
      during the summer, which coincides with the reproductive season and the
      occurrence of most neotropical tadpoles in their natural environment, strong
      indications exist that tadpoles are developing in contaminated ponds. Fipronil is
      one of the primary insecticides used in sugarcane cultivation in Brazil, and
      little is known about its toxic effects on non-target organisms such as tadpoles.
      The purpose of this study was to evaluate the effects of fipronil and its
      metabolites on oxidative stress in Eupemphix nattereri tadpoles after exposure in
      water and sediment at concentrations of 35, 120 and 180ugkg-1. We assessed the
      activities of the antioxidant enzymes glutathione S-transferase (GST), glucose 6
      phosphate dehydrogenase (G6PDH) and catalase (CAT) and lipid peroxidation
      (malondialdehyde, MDA). The results showed that fipronil has an inherent capacity
      to cause oxidative stress in tadpoles, as evidenced by a decrease in CAT activity
      and an increase in lipid peroxidation levels at all concentrations tested.
      Fipronil sulfone also produced elevated MDA levels at two of the tested
      concentrations and increased G6PDH activity in tadpoles exposed to the highest
      concentration of this metabolite but did not affect MDA levels. Our data showed
      that fipronil and its degradation products promoted oxidative stress in Eupemphix
      nattereri tadpoles exposed to environmentally relevant concentrations and could
      lead to a decrease in the long-term physiological performance of these animals,
      leading to detrimental effects at the population level.

PMID- 27870968
TI  - The cardiac maladaptive ATF3-dependent cross-talk between cardiomyocytes and
      macrophages is mediated by the IFNgamma-CXCL10-CXCR3 axis.
AB  - RATIONAL: Pressure overload induces adaptive and maladaptive cardiac remodeling
      processes in the heart. Part of the maladaptive process is the cross-talk between
      cardiomyocytes and macrophages which is dependent on the function of the
      Activating Transcription Factor 3, ATF3. Yet, the molecular mechanism involved in
      cardiomyocytes-macrophages communication leading to macrophages recruitment to
      the heart and cardiac maladaptive remodeling is currently unknown. METHODS AND
      RESULTS: Isolated peritoneal macrophages from either wild type or ATF3-KO mice
      were cultured in serum free medium to collect conditioned medium (CM). CM was
      used to probe an antibody cytokine/chemokine array. The interferon gamma induced
      protein 10kDa, CXCL10, was found to be enriched in wild type macrophages CM. Wild
      type cardiomyocytes treated with CXCL10 in vitro, resulted in significant
      increase in cell volume as compared to ATF3-KO cardiomyocytes. In vivo, pressure
      overload was induced by phenylephrine (PE) infusion using micro-osmotic pumps.
      Consistently, CXCL11 (CXCL10 competitive agonist) and CXCL10 receptor antagonist
      (AMG487) attenuated PE-dependent maladaptive cardiac remodeling. Significantly,
      we show that the expression of the CXCL10 receptor, CXCR3, is suppressed in
      cardiomyocytes and macrophages derived from ATF3-KO mice. CXCR3 is positively
      regulated by ATF3 through an ATF3 transcription response element found in its
      proximal promoter. Finally, mice lacking CXCR3 display a significant reduction of
      cardiac remodeling processes following PE infusion. CONCLUSIONS: Chronic PE
      infusion results in a unique cardiomyocytes-macrophages cross-talk that is
      mediated by IFNgamma. Subsequently, macrophages that are recruited to the heart
      secrete CXCL10 resulting in maladaptive cardiac remodeling mediated by the CXCR3
      receptor. ATF3-KO mice escape from PE-dependent maladaptive cardiac remodeling by
      suppressing the IFNgamma-CXCL10-CXCR3 axis at multiple levels.

PMID- 27870969
TI  - Preliminary experience with high-density electroanatomical mapping for ablation
      of atrial fibrillation - Comparison of mini-basket and novel open irrigated
      magnetic ablation catheter in consecutive patients.
AB  - BACKGROUND: Recently, a novel electroanatomic mapping system enabling rapid and
      automatic acquisition of high-resolution maps has been introduced. Previous
      reports focused on system use in combination with a mini-basket catheter.
      However, a novel system-specific, magnet-enabled ablation catheter eliminates the
      need for the mini-basket catheter and can potentially reduce procedure complexity
      and cost. Here we present our first experience from two consecutive case series
      using both procedural settings. METHODS: In 14 consecutive patients (67+/-9years,
      5 male) with paroxysmal (n=10) or persistent AF (n=4) undergoing de-novo (n=8) or
      repeat (n=6) AF ablation, left atrial electroanatomical maps were acquired with a
      mini-basket and in 22 patients (64+/-9years, 17 male) with paroxysmal (n=4) or
      persistent AF (n=18) undergoing de-novo (n=12) or repeat (n=10) AF ablation with
      the new ablation catheter. RESULTS: Both complete (7.9 [IQR 4.5-16.2] vs 18.8
      [IQR 12.0-25.5] minutes, p=0.005) and partial maps (3.0 [IQR 2.0-4.6] vs 4.5 [IQR
      2.0-6.0] minutes, p=0.014) acquired with mini-basket required significantly
      shorter mapping time and had higher point density: 8832+/-4809 vs 4460+/-3914
      (p=0.014) and 2483+/-1774 vs 1111+/-1926 data points (p=0.002) in partial maps.
      However, procedural (201+/-52 vs 159+/-29min, p=0.004) and fluoroscopy time (33+/
      11 vs 25+/-6min, p=0.005) was significantly higher in the mini-basket group.
      Procedural endpoints and complications rates were similar in both groups.
      CONCLUSION: The high-density mapping system can successfully be used with both
      mini-basket catheters and ablation catheters employed for electro-anatomic
      reconstruction of the left atrium. While mapping is faster and point density
      higher with the mini-basket, procedure and fluoroscopy times are longer. The
      clinical significance of those findings needs to be investigated in future and
      larger studies.

PMID- 27870967
TI  - Osthole inhibits the expressions of collagen I and III through Smad signaling
      pathway after treatment with TGF-beta1 in mouse cardiac fibroblasts.
AB  - BACKGROUND: Osthole, a natural coumarin and bioactive compound isolated from the
      fruit of Cnidium monnieri (L.) Cusson, was reported to prevent isoprenaline
      induced myocardial fibrosis in mice by inhibiting the transforming growth factor
      beta1 (TGF-beta1) expression, but the underlying mechanism is still unclear. The
      aim of this study is to illuminate whether the mechanism of osthole inhibiting
      collagen I and III expressions is associated with Smad signaling pathway in mouse
      cardiac fibroblasts (CFs) treated with TGF-beta1. METHODS: The mouse CFs
      stimulated with TGF-beta1 were cultured and treated with osthole 1.25-5MUg/ml for
      24h. The expressions of alpha-SMA, collagen I, collagen III, TGF-beta receptor I
      (TbetaRI), Smad2/3, phospho-Smad2/3 (P-Smad2/3), Smad4 and Smad7 were detected by
      real-time PCR method and western blot method, respectively. RESULTS: After
      treatment with TGF-beta1 and osthole in CFs, the levels of alpha-SMA expression
      and collagen I and III were reduced by osthole treatment. Accordingly, the ratio
      of collagen I/III had a similar changing trend. Besides, the levels of TbetaRI,
      Smad2/3, P-Smad2/3 and Smad4 expressions were decreased, while the level of Smad7
      expression was increased after treatment with osthole. CONCLUSION: The present
      results demonstrated that osthole could inhibit the collagen I and III
      expressions and their ratio in CFs treated with TGF-beta1 via Smad signaling
      pathway, which might be one of its anti-fibrotic action mechanisms.

PMID- 27870970
TI  - Panoramic characterization of endocardial left atrial activation during human
      persistent AF: Insights from non-contact mapping.
AB  - BACKGROUND: The relative importance of focal drivers, multiple wavelets, rotors
      and endocardial-epicardial circuits in the maintenance of persistent AF remains
      unclear. Our objective was to characterize AF wavefront (WF) dynamics during
      persistent AF. METHODS: The Ensite 3000 (St Jude Medical) non-contact mapping
      system was used to map the LA of 15 patients with persistent AF. Wavefronts were
      classified into planar WFs, rotors or focal WFs. For each new WF the site of
      origin, the unipolar electrogram, and propagation patterns were determined.
      RESULTS: AF was characterized by highly unstable patterns of activation with
      random combinations of 1-2 propagating planar wavefronts alternating with focal
      activations in a dynamic process. Stable reentry circuits and rotors were never
      seen. A total of 499 wavefront patterns were analyzed in this study (416 planar
      wavefronts and 83 focal wavefronts). In an individual patient planar WFs
      accounted for 67+/-35% of activations with lifespans of 98+/-86ms. Focal
      activations accounted for 29.7+/-33.5% of activations with lifespans of 76+/
      95ms. The most common sites for new WF generation were the PVs (33%), LA roof
      (23%), anterior LA (15%), LAA (11%), and posterior LA (8%). The most common
      unipolar electrogram morphologies observed were QS pattern (34%), rS (29%), CFAE
      (26%), QR (7%) and Rs (4%), suggesting that WFs may originate from both the
      endocardial and epicardial surfaces. CONCLUSION: Human persistent AF is
      characterized by the formation of highly unstable WFs consisting of various
      combinations of one to two planar WFs and brief focal activations without any
      evidence of rotors or sustained focal sources.

PMID- 27870972
TI  - MEK/ERK signaling is involved in the role of VEGF and IGF1 in cardiomyocyte
      differentiation of mouse adipose tissue-derived stromal cells.
AB  - BACKGROUND: We found that mouse brown adipose tissue-derived stromal cells
      (BATDCs), but not white adipose tissue-derived stromal cells (WATDCs), could
      spontaneously differentiate into cardiomyocyte-like cells in a simple culture
      medium. This study would find out some critical trophic factors that were
      responsible for such difference in differentiation, and further determine the
      involved signaling pathway. METHODS AND RESULTS: The cardiomyocyte
      differentiation capacity of cells was identified by morphological observations,
      immunofluorescence staining, and evaluation of expression of cardiomyocyte
      specific markers. The amount of vascular endothelial growth factor (VEGF) and
      insulin-like growth factor 1 (IGF1) secreted by cells was determined by ELISA
      analysis. Results indicated that BATDCs secreted higher levels of VEGF and IGF1
      than WATDCs. Supplementation of BATDCs with antibodies against VEGF receptor Flt
      1 or IGF1 receptor Igf-1ralpha significantly suppressed the cardiac
      differentiation capacity of the cells. Additionally, anti-Flt-1 and anti-Igf
      1ralpha antibodies decreased phosphorylation of ERK1/2 in BATDCs. Inhibition of
      MEK/ERK activity by the inhibitor PD0325901 or by RNA interference blunted the
      cardiac differentiation of BATDCs. Loading recombinant VEGF and IGF1, or
      transfecting their expression vectors into WATDCs, promoted cardiac
      differentiation of the cells. Preincubation with PD0325901, before VEGF and IGF1
      supplementation or vector transfections, blocked the stimulation of cardiac
      differentiation in WATDCs. CONCLUSIONS: These findings indicated that VEGF and
      IGF1 were critical factors for the spontaneous cardiac differentiation of BATDCs,
      and MEK/ERK signaling was involved in the role of VEGF and IGF1. VEGF and IGF1
      could be used to promote the development of cardiomyocyte phenotype in WATDCs.

PMID- 27870973
TI  - Transthoracic Doppler echocardiography compared with positron emission tomography
      for assessment of coronary microvascular dysfunction: The iPOWER study.
AB  - BACKGROUND: Coronary microvascular function can be assessed by transthoracic
      Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by
      positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET
      MBFR is regarded the noninvasive reference standard for measuring coronary
      microvascular function but has limited availability. We compared TTDE CFVR with
      PET MBFR in women with angina pectoris and no obstructive coronary artery disease
      and assessed repeatability of TTDE CFVR. METHODS: From a cohort of women with
      angina and no obstructive coronary artery stenosis at invasive coronary
      angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET
      with adenosine was successfully measured in 107 subjects. Repeatability of TTDE
      CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. RESULTS:
      MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR)
      was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearson's correlation
      coefficient was 0.36 (p<0.01). Limits of agreement (2.standard deviation)
      assessed by the Bland-Altman (confidence interval, CI) method was 1.49
      (1.29;1.69) and unaffected by time-interval between examinations. Results were
      similar when adjusting for rate pressure product or focusing on perfusion of the
      left anterior descending artery region. Limits of agreement (CI) for repeated
      CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68)
      and 0.48 (0.22; 0.74), respectively. CONCLUSION: CFVR had a good repeatability,
      but the agreement between CFVR and MBFR was modest. Divergence could be due to
      methodology differences; TTDE estimates flow velocities whereas PET estimates
      myocardial blood flow.

PMID- 27870971
TI  - Modes of death in patients with heart failure and preserved ejection fraction.
AB  - BACKGROUND: Recent studies suggest that reduced right ventricular function is an
      important predictor of outcome in patients with heart failure and preserved
      ejection fraction (HFpEF). Because affected patients suffer from a broad spectrum
      of non-cardiac co-morbidities, it remains unclear, whether they actually die from
      right heart failure (RHF) or as a consequence of other conditions. METHODS:
      Consecutive patients with a confirmed diagnosis of HFpEF were enrolled in this
      prospective registry. Local and external medical records, as well as telephone
      interviews with relatives were used to ascertain modes of death. RHF was accepted
      as a mode of death, if the following criteria were met: 1. right ventricular
      dysfunction assessed by transthoracic echocardiography, and 2. clinical signs of
      right heart decompensation at the time of death. RESULTS: Out of 230 patients
      with complete follow-up, 16.5% (n=38) died after a mean of 30+/-17months. 60.5%
      deaths were classified as cardiovascular and 34.2% as non-cardiovascular. In 5.3%
      patients, the reason for death remained unknown. Of the cardiovascular cases
      (n=23), 91.4% of deaths were attributed to RHF, 4.3% died from stroke and 4.3%
      from sudden cardiac death. Of the non-cardiovascular deaths (n=13), 46.2% of
      deaths were attributed to major infections and 38.4% deaths were related to
      cancer. Other reasons for death included ileus (7.7%) and major bleeding (7.7%).
      CONCLUSION: In our well-characterised HFpEF cohort, more than half of all deaths
      could directly be attributed to RHF. The right ventricle seems to be a meaningful
      therapeutic target in a subset of patients.

PMID- 27870975
TI  - Comparisons of the underlying mechanisms of left atrial remodeling after repeat
      circumferential pulmonary vein isolation with or without additional left atrial
      linear ablation in patients with recurrent atrial fibrillation.
AB  - BACKGROUND: Radiofrequency catheter ablation (RFCA) is a potentially curative
      treatment for atrial fibrillation (AF), however, whether or not additional left
      atrial (LA) linear ablation for recurrent AF adversely affects LA remodeling is
      unknown. METHODS: Thirty-eight patients experiencing AF recurrence after the 1st
      circumferential pulmonary vein isolation (CPVI) underwent a repeat RFCA,
      including 20 and 18 patients receiving a repeat CPVI (group I) or CPVI plus LA
      linear ablation (group II), respectively. 2-D echocardiography was performed
      during sinus rhythm within 24h, at 1-m and 6-m after RFCA. Longitudinal strains
      and strain rate were measured with speckle-tracking echocardiography. The
      standard deviation of contraction duration was defined as LA mechanical
      dispersion. RESULTS: One and two patients experienced AF recurrence after the 2nd
      RFCA in group I and II, respectively (P=NS). The 1st CPVI with AF recurrence did
      not reduce LA size significantly in two groups. After a repeat CPVI, LA diameter
      but not LA maximal and minimal volume was significantly reduced in group I;
      additional LA linear ablation significantly decreased LA diameter, maximal and
      minimal volume in group II. However, there was no significant difference in LA
      emptying function, global and segmental LA strain and strain rate among the
      baseline, 1-m and 6-m follow-up in two groups. RFCA did not significantly
      increase LA mechanical dispersion regardless of the AF ablation strategies.
      CONCLUSIONS: In patients with recurrent AF, a successful repeat CPVI with or
      without additional LA linear ablation reduced LA size without significant
      deleterious effects on LA function and mechanical dispersion.

PMID- 27870974
TI  - Myocardial perfusion in peripheral Raynaud's phenomenon. Evaluation using stress
      cardiovascular magnetic resonance.
AB  - BACKGROUND: Peripheral Raynaud's phenomenon (RP) is either primary (PRP), without
      any coexisting disease or secondary (SRP), due to connective tissue diseases
      (CTD). We hypothesized that adenosine stress cardiovascular magnetic resonance
      (CMR) can assess myocardial perfusion in a population of PRP and SRP. PATIENTS
      METHODS: Twenty CTDs, aged 30.6+/-7.5yrs., 16F/4M, including 9 systemic sclerosis
      (SSc), 4 systemic lupus erythematosus (SLE), 3 mixed connective tissue disease
      (MCTD), 2 polymyositis (PM) and 2 rheumatoid arthritis (RA), with SRP, under
      treatment with calcium blockers, were evaluated by stress CMR and compared with
      age-sex matched PRP and controls. All RP patients were under treatment with
      calcium blockers. Stress perfusion CMR was performed by 1.5T system using
      140mg/kg/min adenosine for 4min and 0.05mmol/kg Gd-DTPA for first-pass perfusion.
      A rest perfusion was performed with the same protocol. Late gadolinium enhanced
      (LGE) images were acquired after another dose of Gd-DTPA. RESULTS: In both PRP,
      SRP, the myocardial perfusion reserve index (MPRI) was significantly reduced
      compared with the controls (1.7+/-0.6 vs 3.5+/-0.4, p<0.001 and 0.7+/-0.2 vs
      3.5+/-0.4, p<0.001, respectively). Furthermore, in SRP, MPRI was significantly
      reduced, compared with PRP (0.7+/-0.2 vs 1.7+/-0.6, p<0.001). Subendo-cardial
      LGE=8.2+/-1.7 of LV mass was revealed in 1 SLE, 1MCTD and 2 SSc, but in none of
      PR patients. CONCLUSIONS: MPRI reduction is common in both PRP and SRP, but it is
      more severe in SRP, even if RP patients are under treatment with calcium
      blockers. Occult fibrosis may coexist with the reduced MPRI in SRP but not in
      PRP.

PMID- 27870976
TI  - Percutaneous coronary intervention and recurrent hospitalizations in elderly
      patients with non ST-segment acute coronary syndrome: The role of frailty.

PMID- 27870977
TI  - Longitudinal treatment patterns with ADP receptor inhibitors after myocardial
      infarction: Insights from the Canadian Observational AntiPlatelet sTudy.
AB  - BACKGROUND: After myocardial infarction (MI) treated with percutaneous coronary
      intervention (PCI), guidelines recommend dual antiplatelet therapy (DAPT) with
      aspirin and an ADP receptor inhibitor (ADPri) for at least 1year. However,
      whether real-world Canadian practice patterns reflect this recommendation is
      unknown. METHODS: We studied 2175 MI patients treated with PCI and discharged
      from 26 Canadian hospitals between 12/2011 and 05/2013 in the Canadian
      Observational Antiplatelet sTudy (COAPT). Hierarchical Cox proportional hazard
      regression modeling was used to determine baseline demographic and clinical
      factors associated with duration of ADPri therapy post-discharge. RESULTS: At
      index-hospitalization discharge, 1597 (73%) patients were treated with
      clopidogrel, 220 (10%) with prasugrel, and 358 (17%) with ticagrelor. ADPri was
      discontinued prior to 1year in 474 (21.8%) patients; discontinuation rates were
      lowest for patients discharged on prasugrel (17.7%), compared with clopidogrel
      (22.5%) or ticagrelor (21.0%), (log rank test, p=0.03). In addition to regional
      variability, factors associated with shorter ADPri duration included older age,
      low body weight, Killip III/IV heart failure, atrial fibrillation, ticagrelor on
      discharge, and bare metal stent use, while longer ADPri duration was associated
      with history of prior MI. CONCLUSIONS: One in five PCI-treated MI patients did
      not complete Canadian guideline-recommended 1-year course of ADPri treatment.
      Premature ADPri discontinuation was most strongly associated with factors that
      increase the risk of bleeding. Further study is required to assess the clinical
      implications of premature ADPri discontinuation on patient outcomes.

PMID- 27870979
TI  - Coronary disease risk assessment in men: Comparison between ASCVD Risk versus
      Framingham.
AB  - INTRODUCTION: This study evaluated the risk of men developing coronary heart
      disease and its determinant variables, comparing these results through two
      validated coronary risk scales. METHODS: A cross sectional epidemiological
      analytical study in which data were collected by spontaneous demand, through a
      semi-structured questionnaire, clinical examination, and blood collection. The
      Chi-square test, logistic regression and Kappa for statistical analysis were
      performed. RESULTS: The study included 637 men. Age was a determining factor
      (p<0.05) in blood pressure (BP) changes, central obesity, BMI, glycemia, total
      cholesterol, LDL and triglycerides. From this group of 637, 252 presented BP
      above the recommended values. It was found that 34.54% of men had high total
      cholesterol, 19.94% had high LDL, 46.78% presented HDL below normal values and
      36.42% had elevated triglycerides. Metabolic syndrome was found in 24.96% of the
      men. With the Framingham scale, 637 men were evaluated, 12.56% were at
      intermediate-risk and 5.49% elevated risk, while on the ASCVD Risk scale 553 men
      were evaluated, and 7.05% had moderate risk and none had high coronary risk. In
      this study, 50.43% of men still had no previous diagnosis for any disease that
      increases the risk factors. CONCLUSIONS: The determinant clinical variables were
      age, blood pressure, smoking, central obesity, race and education. The Framingham
      scale allowed the assessment of cardiac risk of all men in the study, with no age
      restriction or cholesterol value, so in population studies it shows advantages
      over the ASCVD Risk due to its comprehensive feature of including all
      individuals.

PMID- 27870978
TI  - Towards the standardization of stem cell therapy studies for ischemic heart
      diseases: Bridging the gap between animal models and the clinical setting.
AB  - Today there is an increasing demand for heart transplantations for patients
      diagnosed with heart failure. Though, shortage of donors as well as the large
      number of ineligible patients hurdle such treatment option. This, in addition to
      the considerable number of transplant rejections, has driven the clinical
      research towards the field of regenerative medicine. Nonetheless, to date,
      several stem cell therapies tested in animal models fall by the wayside and when
      they meet the criteria to clinical trials, subjects often exhibit modest
      improvements. A main issue slowing down the admission of such therapies in the
      domain of human trials is the lack of protocol standardization between research
      groups, which hampers comparison between different approaches as well as the lack
      of thought regarding the clinical translation. In this sense, given the large
      amount of reports on stem cell therapy studies in animal models reported in the
      last 3years, we sought to evaluate their advantages and limitations towards the
      clinical setting and provide some suggestions for the forthcoming investigations.
      We expect, with this review, to start a new paradigm on regenerative medicine, by
      evoking the debate on how to plan novel stem cell therapy studies with animal
      models in order to achieve more consistent scientific production and accelerate
      the admission of stem cell therapies in the clinical setting.

PMID- 27870980
TI  - A systematic review on perceptual-motor calibration to changes in action
      capabilities.
AB  - Perceptual-motor calibration has been described as a mapping between perception
      and action, which is relevant to distinguish possible from impossible
      opportunities for action. To avoid movement errors, it is relevant to rapidly
      calibrate to immediate changes in capabilities and therefore this study sought to
      explain in what conditions calibration is most efficient. A systematic search of
      seven databases was conducted to identify literature concerning changes in
      calibration in response to changes in action capabilities. Twenty-three papers
      satisfied the inclusion criteria. Data revealed that calibration occurs rapidly
      if there is a good match between the task that requires calibration and the
      sources of perceptual-motor information available for exploration (e.g. when
      exploring maximal braking capabilities by experiencing braking). Calibration can
      take more time when the perceptual-motor information that is available is less
      relevant. The current study identified a number of limitations in the field of
      perceptual-motor research. Most notably, the mean participant age in the included
      studies was between 18 and 33years of age, limiting the generalizability of the
      results to other age groups. Also, due to inconsistent terminology used in the
      field of perceptual-motor research, we argue that investigating calibration in
      older cohorts should be a focus of future research because of the possible
      implications of impaired calibration in an aging society.

PMID- 27870981
TI  - Healthy dietary patterns and incidence of biliary tract and gallbladder cancer in
      a prospective study of women and men.
AB  - BACKGROUND: Whether diet influences the risk of biliary tract cancer (BTC) is
      unknown. We examined the associations of two healthy dietary patterns, including
      a modified Dietary Approach to Stop Hypertension (mDASH) diet and a modified
      Mediterranean (mMED) diet, with the incidence of BTC in a population-based
      prospective study. METHODS: The study population comprised 76,014 Swedish adults
      who were 45-83 years of age and cancer-free at baseline. The mDASH and mMED diets
      were calculated from self-reported dietary data collected by a validated food
      frequency questionnaire. Cox proportional hazards regression models were used to
      estimate hazard ratios (HR) with 95% confidence intervals (CI) adjusted for
      potential confounders. RESULTS: Over 1,010,777 person-years (mean 13.3 years) of
      follow-up, 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23
      intrahepatic BTC cases were ascertained by linkage with the Swedish Cancer
      Register. Adherence to the mDASH and mMED diets was statistically significantly
      inversely associated with risk of extrahepatic BTC (Ptrend <= 0.0003) and
      gallbladder cancer (Ptrend <= 0.005) but not intrahepatic BTC (Ptrend >= 0.11).
      The multivariable HRs (95% CI) for the highest versus lowest tertile of the mDASH
      diet were 0.41 (0.26-0.64) for extrahepatic BTC and 0.36 (0.20-0.64) for
      gallbladder cancer. The corresponding HRs (95% CI) for the mMED diet were
      respectively 0.41 (0.25-0.67) and 0.42 (0.23-0.79). CONCLUSION: Adherence to a
      healthy diet may play a role in reducing the risk of extrahepatic BTC.

PMID- 27870982
TI  - UV and fluorescent spectra study the reaction between 1, 8-Naphthalimide
      derivative and hypochlorite their applications.
AB  - Two simple, efficient turn-on fluorescent probes for hypochlorite have been
      rationally designed and developed by utilizing the oxidation of hypochlorite.
      Notably, probe 1 and 2 displayed rapid and remarkable turn-on responses to ClO-
      in PBS buffer solution (pH7.4). Further, the optical properties of two probes and
      their ClO--addition products were confirmed by density functional theory
      calculations. And detection limits of two probes for ClO- based on the definition
      by IUPAC were calculated for 2.882nM and 0.354MUM. More importantly, cell imaging
      experiments demonstrated that probe 1 was more suitable for detecting the ClO- in
      living A549 cells. And both two probes had the possibility of potentially applied
      in practical applications such as detecting the hypochlorite concentration of tap
      water and river water.

PMID- 27870983
TI  - Modulation of pi-spacer of carbazole-carbazole based organic dyes toward high
      efficient dye-sensitized solar cells.
AB  - The effects of type and position of pi-linker in carbazole-carbazole based dyes
      on their performance in dye-sensitized solar cells (DSSCs) were investigated by
      DFT and TDDFT methods. The calculated electronic energy level, electron density
      composition, charge injection and charge recombination properties were compared
      with those of the high performance CCT3A dye synthesized recently. It is found
      that that mixing a benzothiadizole (B) unit with two thiophene (T) units in the
      pi-spacer can greatly shift absorption wavelength to near infrared region and
      enhance the light harvesting efficiency (LHE) resulting in increasing of short
      circuit current density (Jsc), whereas a thienothiophene unit does not affect
      those properties. However, a B should be not directly connected to the anchoring
      group of the dye because it brings electrolyte to the TiO2 surface which may
      increase charge recombination rate and consequently decrease open circuit voltage
      (Voc). This work shows how type and position of the pi-linker affect the
      performance of DSSCs, and how to modulate those properties. We predicted that the
      designed dye derived from insertion of the B unit in between the two T units
      would have higher performance than CCT3A dye. The insight understanding from this
      study is useful for further design of higher performance dyes by molecular
      engineering.

PMID- 27870984
TI  - Prevalence and molecular characterization of Clostridium difficile isolates from
      a pig slaughterhouse, pork, and humans in Taiwan.
AB  - Clostridium difficile causes antibiotic-associated diarrhea in both humans and
      animals. The ribotype 078, predominant in food animals, is associated with
      community-acquired C. difficile infection, and C. difficile is suggested to be a
      foodborne pathogen. Recently, the C. difficile ribotype 078 lineage emerged in
      patients and pigs in Taiwan. This study aimed to investigate the prevalence and
      molecular characterization of C. difficile isolated from a pig slaughterhouse,
      retail meat, ready-to-eat meals, and humans in Taiwan. We collected samples from
      one slaughterhouse (n=422), 29 retail markets (raw pork, n=62; ready-to-eat pork,
      n=65), and one hospital (non-diarrheal humans, stool, n=317) in 2015. The
      isolated C. difficile were subjected to ribotyping and multilocus variable-number
      tandem-repeat analysis (MLVA). In the slaughterhouse, the isolation rate from
      carcasses was high (23%, 21/92) and ribotype 126 dominated. Scalding water was
      found to have C. difficile contamination (44%, 4/9), and two of the seven
      isolates were ribotype 126. The isolation rates from raw pork and ready-to-eat
      pork were between 20% and 29%. Ribotypes 126, 127, and 014 were found in raw
      pork, whereas ribotype 078 was not identified in this study. Eight isolates-seven
      non-toxigenic isolates and one ribotype 017-were found in non-diarrheal human
      samples. Notably, MLVA showed that ribotype 126 isolates from the slaughterhouse,
      pig stool, colons, carcasses, and scalding water were closely genetically
      related, indicating serious risk for cross-contamination. However, the genetic
      evidence of foodborne transmission from carcasses to food and humans is still
      lacking.

PMID- 27870985
TI  - Effect of ammonium and amino acids on the growth of selected strains of
      Gluconobacter and Acetobacter.
AB  - Acetic acid bacteria (AAB) are a group of microorganisms highly used in the food
      industry. However, its use can be limited by the insufficient information known
      about the nutritional requirements of AAB for optimal growth. The aim of this
      work was to study the effects of different concentrations and sources of nitrogen
      on the growth of selected AAB strains and to establish which nitrogen source best
      encouraged their growth. Two strains of three species of AAB, Gluconobacter
      japonicus, Gluconobacter oxydans and Acetobacter malorum, were grown in three
      different media with diverse nitrogen concentrations (25, 50, 100, and 300mgN/L
      and 1gN/L) as a complete solution of amino acids and ammonium. With this
      experiment, the most favourable medium and the lowest nitrogen concentration
      beneficial for the growth of each strain was selected. Subsequently, under these
      conditions, single amino acids or ammonium were added to media individually to
      determine the best nitrogen sources for each AAB strain. The results showed that
      nitrogen requirements are highly dependent on the nitrogen source, the medium and
      the AAB strain. Gluconobacter strains were able to grow in the lowest nitrogen
      concentration tested (25mgN/L); however, one of the G. oxydans strains and both
      A. malorum strains required a higher concentration of nitrogen (100-300mgN/L) for
      optimal growth. In general, single nitrogen sources were not able to support the
      growth of these AAB strains as well as the complete solution of amino acids and
      ammonium.

PMID- 27870986
TI  - A generalized nonlinear model-based mixed multinomial logit approach for crash
      data analysis.
AB  - The mixed multinomial logit (MNL) approach, which can account for unobserved
      heterogeneity, is a promising unordered model that has been employed in analyzing
      the effect of factors contributing to crash severity. However, its basic
      assumption of using a linear function to explore the relationship between the
      probability of crash severity and its contributing factors can be violated in
      reality. This paper develops a generalized nonlinear model-based mixed MNL
      approach which is capable of capturing non-monotonic relationships by developing
      nonlinear predictors for the contributing factors in the context of unobserved
      heterogeneity. The crash data on seven Interstate freeways in Washington between
      January 2011 and December 2014 are collected to develop the nonlinear predictors
      in the model. Thirteen contributing factors in terms of traffic characteristics,
      roadway geometric characteristics, and weather conditions are identified to have
      significant mixed (fixed or random) effects on the crash density in three crash
      severity levels: fatal, injury, and property damage only. The proposed model is
      compared with the standard mixed MNL model. The comparison results suggest a
      slight superiority of the new approach in terms of model fit measured by the
      Akaike Information Criterion (12.06 percent decrease) and Bayesian Information
      Criterion (9.11 percent decrease). The predicted crash densities for all three
      levels of crash severities of the new approach are also closer (on average) to
      the observations than the ones predicted by the standard mixed MNL model.
      Finally, the significance and impacts of the contributing factors are analyzed.

PMID- 27870988
TI  - Sensitivity and attachment interventions in early childhood: A systematic review
      and meta-analysis.
AB  - A systematic review and meta-analysis of randomized controlled trials (RCT) was
      conducted to determine whether early interventions are effective in improving
      attachment security and parental sensitivity. Electronic databases were searched
      2002-2015 onwards, All RCTs delivered to mothers, fathers or carers, before their
      child's mean age was 36 months, via 1:1 support, group work or guided self-help
      were included. The search was restricted to English Language publications. Study
      Selection, data extraction and quality appraisal were independently undertaken by
      two authors. With regard to analysis, where appropriate, dichotomous data were
      pooled using the Mantel- Haenszel odds ratio method and for continuous data
      descriptive statistics were collected in order to calculate standardized mean
      differences and effect sizes. Four studies met inclusion criteria and were
      divided into two groups: North American & Canadian and South African based
      studies. Combining data from both groups indicates that early interventions
      improve attachment security and improves rates of disorganized attachment. One
      study provided extractable data on the outcome of parental sensitivity which
      shows that early interventions were effective in improving maternal sensitivity
      at 6 and 12 months. Study results generally support the findings of a previous
      review (Bakermans-Kranenburg et al., 2003) which found that early interventions
      improved attachment security and maternal sensitivity.

PMID- 27870989
TI  - Maternal postpartum depressive symptoms predict delay in non-verbal communication
      in 14-month-old infants.
AB  - We investigated the potential relationship between maternal depressive symptoms
      during the postpartum period and non-verbal communication skills of infants at 14
      months of age in a birth cohort study of 951 infants and assessed what factors
      may influence this association. Maternal depressive symptoms were measured using
      the Edinburgh Postnatal Depression Scale, and non-verbal communication skills
      were measured using the MacArthur-Bates Communicative Development Inventories,
      which include Early Gestures and Later Gestures domains. Infants whose mothers
      had a high level of depressive symptoms (13+ points) during both the first month
      postpartum and at 10 weeks were approximately 0.5 standard deviations below
      normal in Early Gestures scores and 0.5-0.7 standard deviations below normal in
      Later Gestures scores. These associations were independent of potential
      explanations, such as maternal depression/anxiety prior to birth, breastfeeding
      practices, and recent depressive symptoms among mothers. These findings indicate
      that infants whose mothers have postpartum depressive symptoms may be at
      increased risk of experiencing delay in non-verbal development.

PMID- 27870987
TI  - Single-arm trial of the second version of an acceptance & commitment therapy
      smartphone application for smoking cessation.
AB  - BACKGROUND: The first randomized trial of a smartphone application (app) for
      adult smoking cessation (SmartQuit 1.0) revealed key features that predict
      cessation. These findings guided the revision of this Acceptance & Commitment
      Therapy (ACT)-based application (SmartQuit 2.0), which was primarily tested to
      examine participant receptivity, short-term cessation and reduction, and the
      relationship between program completion, smoking cessation and reduction.
      Secondarily, outcomes were descriptively compared with the SmartQuit1.0 trial.
      METHOD: Adult participants (78% female, 25% with high school or less education,
      30% unemployed) were recruited into the single-arm pilot trial (N=99) of
      SmartQuit 2.0 with a two-month follow-up (85% retention). RESULTS: Regarding
      receptivity, 84% of participants were satisfied with SmartQuit 2.0 (vs. 59% for
      SmartQuit1.0), 73% would recommend it to a friend (vs. 48% for SmartQuit1.0), 81%
      found the ACT exercises useful for quitting (vs. 44% for SmartQuit1.0). At the 2
      month follow-up, the quit rates were 21% for 7-day point prevalence (vs. 23% for
      SmartQuit1.0), 11% for 30-day point prevalence (vs. 13% for SmartQuit1.0), and
      75% of participants reduced their smoking frequency (vs. 57% for SmartQuit1.0).
      Among program completers (24% of total sample), the quit rates were 33% for 7-day
      point prevalence, 28% for 30-day point prevalence, and 88% of participants
      reduced their smoking frequency. CONCLUSIONS: The revised app had high user
      receptivity, modest quit rates, and high smoking reduction rates. Program
      completion may be key to boosting the app's effectiveness.

PMID- 27870990
TI  - Memory by association: Integrating memories prolongs retention by two-year-olds.
AB  - Recalling one memory often leads to the recollection of other memories that share
      overlapping features. This phenomenon, spreading activation, was originally
      documented in studies conducted with verbal adults, and more recently, it has
      been demonstrated with preverbal infants. Here, we examine the effect of
      spreading activation on long-term retention by 2-year-olds. Participants were
      tested in the Visual Recognition Memory (VRM) paradigm and the deferred imitation
      paradigm. Typically, infants of this age exhibit retention in the VRM paradigm
      for 24h, while they exhibit retention in the deferred imitation paradigm for at
      least 8 weeks. In the present experiment, we paired these tasks together during
      original encoding and tested infants after an 8-week delay. Two-year-olds
      exhibited retention in both tasks. That is, when these two tasks initially
      occurred together - one task that is extremely memorable and one that is not -
      retrieving the memory of the more memorable task cued retrieval of the less
      memorable task, extending its longevity.

PMID- 27870991
TI  - Potts Hamiltonian models of protein co-variation, free energy landscapes, and
      evolutionary fitness.
AB  - Potts Hamiltonian models of protein sequence co-variation are statistical models
      constructed from the pair correlations observed in a multiple sequence alignment
      (MSA) of a protein family. These models are powerful because they capture higher
      order correlations induced by mutations evolving under constraints and help
      quantify the connections between protein sequence, structure, and function
      maintained through evolution. We review recent work with Potts models to predict
      protein structure and sequence-dependent conformational free energy landscapes,
      to survey protein fitness landscapes and to explore the effects of epistasis on
      fitness. We also comment on the numerical methods used to infer these models for
      each application.

PMID- 27870992
TI  - Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB
      radiation-induced skin injury in mice.
AB  - This study aimed to investigate the feasibility of producing semisolid
      formulations based on nanocapsule suspensions containing the association of the
      coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions.
      Furthermore, we studied their application as an alternative for the treatment of
      inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model
      of injury induced by UVB-radiation was employed. All semisolids presented pH
      close to 5.5, drug content above 95% and mean diameter on the nanometric range,
      after redispersion in water. Besides, the semisolids presented non-Newtonian flow
      with pseudoplastic behavior and suitable spreadability factor values. The results
      also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with
      higher vitamin E acetate concentration reduced in 73+/-8% the UVB radiation
      induced ear edema. Moreover, all formulations tested were able to reduce
      inflammation parameters evaluated through MPO activity and histological procedure
      on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10
      reduced oxidative parameters assessment through the non-protein thiols levels and
      lipid peroxidation. This way, the semisolids based on nanocapsules may be
      considered a promising approach for the treatment and prevention of skin
      inflammation diseases.

PMID- 27870993
TI  - DLVO, hydrophobic, capillary and hydrodynamic forces acting on bacteria at solid
      air-water interfaces: Their relative impact on bacteria deposition mechanisms in
      unsaturated porous media.
AB  - Experimental and modeling studies were performed to investigate bacteria
      deposition behavior in unsaturated porous media. The coupled effect of different
      forces, acting on bacteria at solid-air-water interfaces and their relative
      importance on bacteria deposition mechanisms was explored by calculating
      Derjaguin-Landau-Verwey-Overbeek (DLVO) and non-DLVO interactions such as
      hydrophobic, capillary and hydrodynamic forces. Negatively charged non-motile
      bacteria and quartz sands were used in packed column experiments. The
      breakthrough curves and retention profiles of bacteria were simulated using the
      modified Mobile-IMmobile (MIM) model, to identify physico-chemical attachment or
      physical straining mechanisms involved in bacteria retention. These results
      indicated that both mechanisms might occur in both sand. However, the attachment
      was found to be a reversible process, because attachment coefficients were
      similar to those of detachment. DLVO calculations supported these results: the
      primary minimum did not exist, suggesting no permanent retention of bacteria to
      solid-water and air-water interfaces. Calculated hydrodynamic and resisting
      torques predicted that bacteria detachment in the secondary minimum might occur.
      The capillary potential energy was greater than DLVO, hydrophobic and
      hydrodynamic potential energies, suggesting that film straining by capillary
      forces might largely govern bacteria deposition under unsaturated conditions.

PMID- 27870994
TI  - Landscape changes in a neotropical forest-savanna ecotone zone in central Brazil:
      The role of protected areas in the maintenance of native vegetation.
AB  - In the Amazon-savanna ecotone in northwest Brazil, the understudied Araguaia
      River Basin contains high biodiversity and seasonal wetlands. The region is
      representative of tropical humid-dry ecotone zones, which have experienced
      intense land use and land cover (LULC) conversions. Here we assessed the LULC
      changes for the last four decades in the central portion of the Araguaia River
      Basin to understand the temporal changes in the landscape composition and
      configuration outside and inside protected areas. We conducted these analyzes by
      LULC mapping and landscape metrics based on patch classes. During this period,
      native vegetation was reduced by 26%. Forests were the most threatened
      physiognomy, with significant areal reduction and fragmentation. Native
      vegetation cover was mainly replaced by croplands and pastures. Such replacement
      followed spatial and temporal trends related to the implementation of protected
      areas and increases in population cattle herds. The creation of most protected
      areas took place between 1996 and 2007, the same period during which the
      conversion of the landscape matrix from natural vegetation to agriculture
      occurred. We observed that protected areas mitigate fragmentation, but their
      roles differ according to their location and level of protection. Still, we argue
      that landscape characteristics, such as suitability for agriculture, also
      influence landscape conversions and should be considered when establishing
      protected areas. The information provided in this study can guide new research on
      species conservation and landscape planning, as well as improve the understanding
      of the impacts of landscape composition and configuration changes.

PMID- 27870995
TI  - Agronomic assessment of pyrolysed food waste digestate for sandy soil management.
AB  - The digestate (DFW) of an industrial food waste treatment plant was pyrolysed for
      production of biochar for its direct application as bio-fertilizer or soil
      enhancer. Nutrient dynamics and agronomic viability of the pyrolysed food waste
      digestate (PyD) produced at different temperatures were evaluated using
      germination index (GI), water retention/availability and mineral sorption as
      indicators when applied on arid soil. The pyrolysis was found to enrich P, K and
      other micronutrients in the biochar at an average enrichment factor of 0.87. All
      PyD produced at different temperatures indicated significantly low phytotoxicity
      with GI range of 106-168% and an average water retention capacity of 40.2%.
      Differential thermogravimetric (DTG) thermographs delineated the stability of the
      food waste digestate pyrolysed at 500  degrees C (PyD500) against the degradation
      of the digestate food waste despite the latter poor nutrient sorption potential.
      Plant available water in soil is 40% when treated with 100 g of digestate per kg
      soil, whereas PyD500 treated soil indicated minimal effect on plant available
      water, even with high application rates. However, the positive effects of PyD on
      GI and the observed enrichment in plant macro and micronutrients suggest
      potential agronomic benefits for PyD use, in addition to the benefits from energy
      production from DFW during the pyrolysis process.

PMID- 27870996
TI  - Design and performance evaluation of a 1000-year evapotranspiration-capillary
      surface barrier.
AB  - Surface barrier technology is used to isolate radioactive waste and to reduce or
      eliminate recharge water to the waste zone for 1000 years or longer. However, the
      design and evaluation of such a barrier is challenging because of the extremely
      long design life. After establishing a set of design and performance objectives,
      a package of design solutions was developed for 1000-year surface barriers over
      nuclear waste sites. The Prototype Hanford Barrier (PHB) was then constructed in
      1994 in the field over an existing waste site as a demonstration. The barrier was
      tested to evaluate surface-barrier design and performance at the field scale
      under conditions of enhanced and natural precipitation and of no vegetation. The
      monitoring data demonstrate that the barrier satisfied nearly all objectives in
      the past two decades. The PHB far exceeded the Resource Conservation and Recovery
      Act criteria, functioned in Hanford's semiarid climate, limited drainage to well
      below the 0.5 mm yr-1 performance criterion, limited runoff, and minimized
      erosion and bio-intrusion. Given the two-decade record of successful performance
      and consideration of the processes and mechanisms that could affect barrier
      stability and hydrology in the future, the results suggest the PHB is very likely
      to perform for its 1000-year design life. This conclusion is based on two
      assumptions: (1) the exposed subgrade receives protection against erosion and (2)
      institutional controls prevent inadvertent human activity at the barrier. The PHB
      design can serve as the basis for site-specific barriers over waste sites
      containing underground nuclear waste, uranium mine tailings, and hazardous mine
      waste.

PMID- 27870997
TI  - Comparative efficacy of psychological therapies for improving mental health and
      daily functioning in irritable bowel syndrome: A systematic review and meta
      analysis.
AB  - Previous meta-analyses have shown that psychotherapy improves gastrointestinal
      symptoms in adults with irritable bowel syndrome (IBS); however, the impact on
      functioning in daily activities is unknown. Meta-analysis was used to estimate
      the effect of psychotherapy on mental health and daily functioning in adults with
      IBS. An extensive literature search located 28 eligible randomized controlled
      trials (RCTs) providing outcome data for mental health and 18 RCTs providing data
      for daily functioning. Compared to a mixed group of control conditions,
      psychotherapy produced significantly greater improvements to mental health (d
      =0.41) and daily functioning (d-=0.43). Cognitive behavior therapy (CBT) was
      evaluated in the largest number of trials (21 trials), followed by hypnosis (4
      trials), psychodynamic (3 trials), and relaxation (2 trials). The
      psychotherapeutic modalities were comparable with respect to their effect on
      mental health. CBT produced the greatest improvements to daily functioning, and
      this effect was significantly larger than that produced by relaxation therapy.
      These results have important clinical implications for treatment of adults with
      IBS.

PMID- 27870998
TI  - Supporting metabolomics with adaptable software: design architectures for the end
      user.
AB  - Large and disparate sets of LC-MS data are generated by modern metabolomics
      profiling initiatives, and while useful software tools are available to annotate
      and quantify compounds, the field requires continued software development in
      order to sustain methodological innovation. Advances in software development
      practices allow for a new paradigm in tool development for metabolomics, where
      increasingly the end-user can develop or redeploy utilities ranging from simple
      algorithms to complex workflows. Resources that provide an organized framework
      for development are described and illustrated with LC-MS processing packages that
      have leveraged their design tools. Full access to these resources depends in part
      on coding experience, but the emergence of workflow builders and pluggable
      frameworks strongly reduces the skill level required. Developers in the
      metabolomics community are encouraged to use these resources and design content
      for uptake and reuse.

PMID- 27870999
TI  - Sparse Bayesian registration of medical images for self-tuning of parameters and
      spatially adaptive parametrization of displacements.
AB  - We extend Bayesian models of non-rigid image registration to allow not only for
      the automatic determination of registration parameters (such as the trade-off
      between image similarity and regularization functionals), but also for a data
      driven, multiscale, spatially adaptive parametrization of deformations. Adaptive
      parametrizations have been used with success to promote both the regularity and
      accuracy of registration schemes, but so far on non-probabilistic grounds -
      either as part of multiscale heuristics, or on the basis of sparse optimization.
      Under the proposed model, a sparsity-inducing prior on transformation parameters
      complements the classical smoothness-inducing prior, and favors parametrizations
      that use few degrees of freedom. As a result, finer bases get introduced only in
      the presence of coherent image information and motion, while coarser bases ensure
      better extrapolation of the motion to textureless, uninformative regions. The
      space of possible parametrizations consists of arbitrary combinations of basis
      functions chosen among any preset, widely overcomplete (and typically multiscale)
      dictionary. Inference is tackled in an efficient Variational Bayes framework. In
      addition we propose a flexible mixture-of-Gaussian model of data that proves to
      be more faithful for a variety of image modalities than the sum-of-squared
      differences. The performance of the proposed approach is demonstrated on time
      series of (cine and tagged) magnetic resonance and echocardiographic cardiac
      images. The proposed algorithm matches the state-of-the-art on benchmark datasets
      evaluating accuracy of motion and strain, and is highly automated.

PMID- 27871000
TI  - Comparison of atlas-based techniques for whole-body bone segmentation.
AB  - We evaluate the accuracy of whole-body bone extraction from whole-body MR images
      using a number of atlas-based segmentation methods. The motivation behind this
      work is to find the most promising approach for the purpose of MRI-guided
      derivation of PET attenuation maps in whole-body PET/MRI. To this end, a variety
      of atlas-based segmentation strategies commonly used in medical image
      segmentation and pseudo-CT generation were implemented and evaluated in terms of
      whole-body bone segmentation accuracy. Bone segmentation was performed on 23
      whole-body CT/MR image pairs via leave-one-out cross validation procedure. The
      evaluated segmentation techniques include: (i) intensity averaging (IA), (ii)
      majority voting (MV), (iii) global and (iv) local (voxel-wise) weighting atlas
      fusion frameworks implemented utilizing normalized mutual information (NMI),
      normalized cross-correlation (NCC) and mean square distance (MSD) as image
      similarity measures for calculating the weighting factors, along with other atlas
      dependent algorithms, such as (v) shape-based averaging (SBA) and (vi) Hofmann's
      pseudo-CT generation method. The performance evaluation of the different
      segmentation techniques was carried out in terms of estimating bone extraction
      accuracy from whole-body MRI using standard metrics, such as Dice similarity
      (DSC) and relative volume difference (RVD) considering bony structures obtained
      from intensity thresholding of the reference CT images as the ground truth.
      Considering the Dice criterion, global weighting atlas fusion methods provided
      moderate improvement of whole-body bone segmentation (DSC= 0.65 +/- 0.05)
      compared to non-weighted IA (DSC= 0.60 +/- 0.02). The local weighed atlas fusion
      approach using the MSD similarity measure outperformed the other strategies by
      achieving a DSC of 0.81 +/- 0.03 while using the NCC and NMI measures resulted in
      a DSC of 0.78 +/- 0.05 and 0.75 +/- 0.04, respectively. Despite very long
      computation time, the extracted bone obtained from both SBA (DSC= 0.56 +/- 0.05)
      and Hofmann's methods (DSC= 0.60 +/- 0.02) exhibited no improvement compared to
      non-weighted IA. Finding the optimum parameters for implementation of the atlas
      fusion approach, such as weighting factors and image similarity patch size, have
      great impact on the performance of atlas-based segmentation approaches. The voxel
      wise atlas fusion approach exhibited excellent performance in terms of cancelling
      out the non-systematic registration errors leading to accurate and reliable
      segmentation results. Denoising and normalization of MR images together with
      optimization of the involved parameters play a key role in improving bone
      extraction accuracy.

PMID- 27871001
TI  - Identification of miRNA from Bouteloua gracilis, a drought tolerant grass, by
      deep sequencing and their in silico analysis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate
      signal transduction, development, metabolism, and stress responses in plants
      through post-transcriptional degradation and/or translational repression of
      target mRNAs. Several studies have addressed the role of miRNAs in model plant
      species, but miRNA expression and function in economically important forage
      crops, such as Bouteloua gracilis (Poaceae), a high-quality and drought-resistant
      grass distributed in semiarid regions of the United States and northern Mexico
      remain unknown. RESULTS: We applied high-throughput sequencing technology and
      bioinformatics analysis and identified 31 conserved miRNA families and 53 novel
      putative miRNAs with different abundance of reads in chlorophyllic cell cultures
      derived from B. gracilis. Some conserved miRNA families were highly abundant and
      possessed predicted targets involved in metabolism, plant growth and development,
      and stress responses. We also predicted additional identified novel miRNAs with
      specific targets, including B. gracilis ESTs, which were detected under drought
      stress conditions. CONCLUSIONS: Here we report 31 conserved miRNA families and 53
      putative novel miRNAs in B. gracilis. Our results suggested the presence of
      regulatory miRNAs involved in modulating physiological and stress responses in
      this grass species.

PMID- 27871002
TI  - Coating nanoparticles with tunable surfactants facilitates control over the
      protein corona.
AB  - Nanoparticles with long blood circulation time are a prerequisite for targeted
      drug delivery. To make the nanoparticles invisible for phagocytizing cells,
      functional moieties on the particle surface are believed to be necessary to
      attract specific so-called 'stealth' proteins forming a protein 'corona'.
      Currently, covalent attachment of those moieties represents the only way to
      achieve that attraction. However, that approach requires a high synthetic effort
      and is difficult to control. Therefore, we present the coating of model
      nanoparticles with biodegradable polymeric surfactants as an alternative method.
      The thermodynamic parameters of the coating process can be tuned by adjusting the
      surfactants' block lengths and hydrophilicity. Consequently, the unspecific
      protein adsorption and aggregation tendency of the particles can be controlled,
      and stealth proteins inhibiting cell uptake are enriched on their surface. This
      non-covalent approach could be applied to any particle type and thus facilitates
      tuning the protein corona and its biological impact.

PMID- 27871003
TI  - Magnetic mesoporous nanospheres anchored with LyP-1 as an efficient pancreatic
      cancer probe.
AB  - Immobilization of a ligand that selectively interacts with cancer cells to
      nanomaterials can enhance their diagnostic and therapeutic efficiency. In this
      study, we firstly demonstrate the high expression of receptor for cyclic nine
      amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys) in both mouse and
      human pancreatic cancer. Based on these findings, sub-50 nm multifunctional
      superparamagnetic mesoporous nanospheres with surface modified with LyP-1 are
      rationally designed. Theses nanospheres have a core of silica-protected magnetite
      nanoparticle and a shell of FITC-labeled mesoporous silica, and they are able to
      specifically recognize and conjugate with the pancreatic cancer cell in vitro, as
      verified by the combined techniques of fluorescent imaging and T2 weight magnetic
      resonance imaging. After systematic administration, these LyP-1 immobilized
      nanospheres are found to actively target to mouse orthotopic xenograft of
      pancreatic cancer, which opens up the door for applications in early probing and
      diagnosis of pancreatic cancer by the multimodal imaging.

PMID- 27871004
TI  - BDE-47 exposure changed the immune function of haemocytes in Mytilus edulis: An
      explanation based on ROS-mediated pathway.
AB  - Brominated Tetra-BDE (BDE-47), is suggested to be widely distributed in marine
      environments and highly accumulated in marine organisms. Blue mussel Mytilus
      edulis is a sentinel organism that is commonly used for monitoring chemical
      contaminants in coastal ecosystems, and its haemocytes play an essential role in
      immune function. Therefore, we estimated the effects of BDE-47 exposure on the M.
      edulis haemocytes' immune function under controlled laboratory conditions. The
      study found the following results: (1) BDE-47 exposure increased the mortality of
      the haemocytes and decreased the total haemocyte counts. The ultrastructure and
      microstructure in the haemocytes were significantly changed, and the micronucleus
      frequency was increased steadily in a concentration-dependent manner, inferring
      that cellular and molecular damages occur during the exposure. (2) The immune
      function of the haemocytes was estimated from lysosomal and phagocytic changes.
      The lysosomal membrane stability was significantly disrupted compared to the
      control according to neutral red retention time changes, and the phagocytic
      ability was reduced significantly. Two lysosomal enzymes, acid phosphatases and
      alkaline phosphatases, presented similar increasing trends during the treatment.
      (3) BDE-47 exposure significantly induced the overproduction of reactive oxygen
      species and malondialdehyde in a clear time- and concentration-dependent manner,
      suggesting the occurrence of oxidative stress. We thus presumed that BDE-47
      exposure affected the immune function of the mussel's haemocytes, and an ROS
      mediated pathway might be one of the possible explanations for the observation.

PMID- 27871005
TI  - Nickel affects gill and muscle development in oriental fire-bellied toad (Bombina
      orientalis) embryos.
AB  - The developmental toxicity of nickel was examined in the embryos of Bombina
      orientalis, a common amphibian in Korea. Based on a standard frog embryo
      teratogenesis assay, the LC50 and EC50 for malformation of nickel after 168h of
      treatment were 33.8MUM and 5.4MUM, respectively. At a lethal concentration
      (100MUM), nickel treatment decreased the space between gill filaments and caused
      epithelial swelling and abnormal fusion of gill filaments. These findings suggest
      that nickel affects the functional development of gills, leading to embryonic
      death. At sublethal concentrations (1-10MUM), nickel produced multiple embryonic
      abnormalities, including bent tail and tail dysplasia. At 10MUM, nickel
      significantly decreased tail length and tail muscle fiber density in tadpoles,
      indicating inhibition of myogenic differentiation. Before hatching, the pre
      muscular response to muscular response stages (stages 26-31) were the most
      sensitive period to nickel with respect to tail muscle development. During these
      stages, MyoD mRNA was upregulated, whereas myogenic regulatory factor 4 mRNA was
      downregulated by 0.1MUM nickel. Calcium-dependent kinase activities in muscular
      response stage embryos were significantly decreased by nickel, whereas these
      activities were restored by exogenous calcium. In tadpoles, 10MUM nickel
      significantly decreased the expression of the myosin heavy chain and the 12/101
      muscle marker protein in the tail. Expression was restored by exogenous calcium.
      Our results indicate that nickel affects muscle development by disrupting calcium
      dependent myogenesis in developing B. orientalis embryos.

PMID- 27871006
TI  - Evaluating the use of friend or family controls in epidemiologic case-control
      studies.
AB  - BACKGROUND: Traditional methodologies for identifying and recruiting controls in
      epidemiologic case-control studies, such as random digit dialing or neighborhood
      walk, suffer from declining response rates. Here, we revisit the feasibility and
      comparability of using alternative sources of controls, specifically friend and
      family controls. METHODS: We recruited from a recently completed case-control
      study of non-Hodgkin lymphoma (NHL) among women in Los Angeles County where
      controls from the parent study were ascertained by neighborhood walk. We
      calculated participation rates and compared questionnaire responses between the
      friend/family controls and the original matched controls from the parent study.
      RESULTS: Of the 182 NHL case patients contacted, 111 (61%) agreed to participate
      in our feasibility study. 70 (63%) provided contact information for potential
      friend and/or family member controls. We were able to successfully contact and
      recruit a friend/family member for 92% of the case patients. This represented 46
      friend controls and 54 family controls. Family controls significantly differed
      from original matched controls by sex and household income. Other characteristics
      were similar between friend controls and the original study's neighborhood
      controls. CONCLUSION: The apparent comparability of neighborhood controls to
      friend and family controls among respondents in this study suggests that these
      alternative methods of control identification can serve as a complementary source
      of eligible controls in epidemiologic case-control studies.

PMID- 27871008
TI  - Production cross sections of radioisotopes from 3He-particle induced nuclear
      reactions on natural titanium.
AB  - Excitation functions were measured using the stacked-foil method for the
      natTi(3He,x)44mSc, 46m+gSc, 47Sc, 48Sc, 48V and 48Cr nuclear processes up to
      68MeV. Our new cross-section data were compared with the earlier reported values
      as well as the evaluated theoretical predictions by means of the TALYS 1.6 code
      as compiled in the TENDL-2015 library. The new data show acceptable agreement
      with the previous experimental values in the overlapping energy regions, however
      only a partial agreement was found in the case of the results of the nuclear
      reaction model code. The present work not only strengthens the experimental
      datasets of the above processes but also provides new cross-section values above
      36MeV where only one dataset is available for each reaction.

PMID- 27871007
TI  - A precise measurement of the 117mSn half-life.
AB  - The 117mSn isotope was produced via fast, 14.1MeV neutron activation of natural
      tin and studied with a background shielded HPGe detector. To enable time-resolved
      gamma-ray spectroscopy to precisely measure the half-life of 117mSn, a commercial
      DAQ was replaced with a CAMAC-based analogue DAQ. The deadtime response of the
      applied DAQ was verified for the measurement. The half-life of 117mSn was
      measured to be 13.91+/-0.03 days and the I(158.6keV)/I(156.0keV) gamma-ray ratio
      was measured to be 43.6+/-1.5.

PMID- 27871009
TI  - Malignant nerve sheath tumor involving glossopharyngeal, vagus and spinal nerve
      with intracranial-extracranial extension and systemic metastases in a patient
      with type 1 neurofibromatosis: A case report.
AB  - INTRODUCTION: Intracranial malignant peripheral nerve sheath tumors are an
      extremely rare pathology with a high morbidity and mortality. Epidemiological,
      clinical and prognostic data are scarce and with little certainty in the
      literature. The aim of this paper is to report for first time in English
      literature, the case of a patient with type 1 neurofibromatosis, who presented a
      malignant peripheral nerve sheath tumor that involved the left glossopharyngeal,
      vagus and spinal nerves with intracranial and extracranial extension through
      jugular foramen and systemic metastases. PRESENTATION OF CASE: A 37 years-old
      female patient with malnutrition and Villarets syndrome. It was confirmed by
      brain magnetic resonance imaging and PET-CT the presence of a neoplasic lesion
      which was radiologically compatible with malignant peripheral nerve sheath tumor
      with systemic metastases. Partial surgical resection was performed; the patient
      postoperative course was without significant clinical improvement but with added
      peripheral facial palsy. The patient did not accept adjuvant management because
      of personal reasons. DISCUSSION AND CONCLUSION: Behavior therapy is unclear due
      to the low frequency of the disease and the lack of case series, representing a
      challenge for the physician in its approach and a poor prognosis for the patient.

PMID- 27871010
TI  - Diagnostic challenges in a patient with myocardial tuberculoma: A case report.
AB  - INTRODUCTION: Tuberculosis can affect any organ of the body, including the heart.
      PRESENTATION OF CASE: An 18-year old woman presented with a multifocal
      tuberculosis infection involving abdominal lymph nodes, a sternotomy wound, an
      abscess of the abdominal wall and most notably a myocardial tuberculoma.
      Establishing the diagnosis of the myocardial tuberculoma was challenging mainly
      due to the location within the heart. Initially a diagnostic percutaneous femoral
      vascular catheter guided biopsy of the right atrial mass was performed, but later
      open surgery involving median sternotomy was needed. The patient recovered fully
      after surgery and nine months treatment with anti-tuberculosis drugs. DISCUSSION:
      The optimal length of treatment for myocardial tuberculoma is unknown. Medical
      treatment for six months might be enough regardless whether surgery is performed
      or not. CONCLUSION: Myocardial tuberculoma requires culture from the infected
      tissue for confirmed diagnosis and might be successfully treated with anti
      tuberculosis drugs only. Indications for surgery include uncertain diagnosis,
      poor response to medical treatment or cardiac complications.

PMID- 27871011
TI  - Multiple concurrent bilateral groin hernias in a single patient; a case report
      and a review of uncommon groin hernias: A possible source of persistent pain
      after successful repair.
AB  - INTRODUCTION: The wide use of laparoscopy for groin hernia repair has unveiled
      "hidden hernias" silently residing in this area. During the open repair of the
      presenting hernia, the surgeon was often unaware of these occult hernias. These
      patients postoperatively may present with unexplained chronic groin or pelvic
      pain. PRESENTATION OF CASE: Rare groin hernias are defined according to their
      anatomical position. Challenges in the diagnosis and management of occult rare
      groin hernias are discussed. These problems are illustrated by a unique case
      report of multiple (six) coexisting groin hernias, whereof five were occult and
      two were rare. DISCUSSION: Rare groin hernias are uncommon because they are
      difficult to diagnose clinically and are not routinely looked for. They are often
      occult and may coexist with other inguinal hernias, thus posing a diagnostic and
      treatment challenge to the surgeon, especially if there is persistent groin pain
      after "successful" repair. MRI is the most accurate preoperative and
      postoperative diagnostic tool, if there is a clinical suspicion that the patient
      might have an occult hernia. CONCLUSION: Preperitoneal endoscopic approach is the
      recommended method in confirming the diagnosis and management of occult groin
      hernias. A sound knowledge of groin anatomy and a thorough preperitoneal
      inspection of all possible sites for rare groin hernias are needed to diagnose
      and repair all defects. The preperitoneal mesh repair with adequate overlap of
      all hernia orifices is the recommended treatment of choice.

PMID- 27871012
TI  - Algorithm based on the short-term Renyi entropy and IF estimation for noisy EEG
      signals analysis.
AB  - Stochastic electroencephalogram (EEG) signals are known to be nonstationary and
      often multicomponential. Detecting and extracting their components may help
      clinicians to localize brain neurological dysfunctionalities for patients with
      motor control disorders due to the fact that movement-related cortical activities
      are reflected in spectral EEG changes. A new algorithm for EEG signal components
      detection from its time-frequency distribution (TFD) has been proposed in this
      paper. The algorithm utilizes the modification of the Renyi entropy-based
      technique for number of components estimation, called short-term Renyi entropy
      (STRE), and upgraded by an iterative algorithm which was shown to enhance
      existing approaches. Combined with instantaneous frequency (IF) estimation, the
      proposed method was applied to EEG signal analysis both in noise-free and noisy
      environments for limb movements EEG signals, and was shown to be an efficient
      technique providing spectral description of brain activities at each electrode
      location up to moderate additive noise levels. Furthermore, the obtained
      information concerning the number of EEG signal components and their IFs show
      potentials to enhance diagnostics and treatment of neurological disorders for
      patients with motor control illnesses.

PMID- 27871013
TI  - Tri- and tetravalent mannoclusters cross-link and aggregate BC2L-A lectin from
      Burkholderia cenocepacia.
AB  - The opportunistic Gram-negative bacterium Burkholderia cenocepacia causes lethal
      infections in cystic fibrosis patients. Multivalent mannoside derivatives were
      prepared as potential inhibitors of lectin BC2L-A, one of the virulence factors
      deployed by B. cenocepacia in the infection process. An (alpha1->2)-thio-linked
      mannobioside mimic bearing an azide functionalized aglycon was conjugated to
      different multivalent scaffolds such as propargylated calix[4]arenes, methyl
      gallate and pentaerythritol by azide-alkyne 1,3-dipolar cycloaddition. The
      interaction between the glycoclusters and the mannose binding BC2L-A lectin from
      B. cenocepacia was examined by isothermal microcalorimetry, surface plasmon
      resonance, inhibition of yeast agglutination and analytical ultracentrifugation.

PMID- 27871014
TI  - Tooth wear pattern analysis in a sample of Italian Early Bronze Age population.
      Proposal of a 3-D sampling sequence.
AB  - OBJECTIVE: The purpose of this study was to assess the prevalence, distribution
      and intensity of tooth wear in a sample of an ancient Italian population in order
      to explain the pattern in terms of dietary habits and/or non-dietary tooth-use
      behaviors during the Early Bronze Age, with a focus on possible age-group and sex
      differences. DESIGN: Well-preserved permanent teeth of individuals from the
      Bronze Age site of Ballabio (Lecco) in northern Italy were examined for tooth
      wear by different methods. Eight 3D models of teeth at increasing severity of
      wear were created. RESULTS: In total, 357 permanent teeth belonging to male and
      female individuals were included in the study. Dental wear was present in 96.6%
      of the total sample. Males showed significantly greater levels of wear than
      females in the mandibular teeth. Both sexes exhibited a significantly different
      wear direction between the anterior (oblique and flat) and posterior (oblique and
      concave) teeth. Significant age differences were observed in the direction and
      level of wear in the incisors, canines and premolars, with higher wear in the
      older group. Complete and rotatable virtual 3D images of different wear patterns
      are proposed. CONCLUSIONS: The findings of the present study confirm the data
      from archaeological studies on this site and on northern Italian habits during
      the Early Bronze Age suggesting a diet rich in vegetables. The observed wear
      patterns can be related both to the diet of this Bronze age population, based on
      hard and abrasive food requiring vigorous mastication, and to sex differences in
      cultural practices.

PMID- 27871015
TI  - The Generalized Problematic Internet Use Scale 2: Validation and test of the
      model to Facebook use.
AB  - The main goals of the present study were to test the psychometric properties of a
      Portuguese version of the GPIUS2 (Generalized Problematic Internet Use Scale 2,
      Caplan, 2010), and to test whether the cognitive-behavioral model proposed by
      Caplan (2010) replicated in the context of Facebook use. We used a sample of 761
      Portuguese adolescents (53.7% boys, 46.3% girls, mean age = 15.8). Our results
      showed that the data presented an adequate fit to the original model using
      confirmatory factor analysis. The scale presented also good internal consistency
      and adequate construct validity. The cognitive-behavioral model was also
      applicable to the Facebook context, presenting good fit. Consistently with
      previous findings we found that preference for online social interaction and the
      use of Facebook to mood regulation purposes, predicted positively and
      significantly the deficient self-regulation in Facebook use, which in turn was a
      significant predictor of the negative outcomes associated with this use.

PMID- 27871016
TI  - Predicting school adjustment from multiple perspectives on parental behaviors.
AB  - Past research supported the importance of parental autonomy support, involvement,
      and structure for student outcomes. The goal of this study was to test the
      contribution of these behaviors from mothers and fathers in predicting
      adolescents' adjustment in school using a multi-informant approach. A sample of
      522 adolescents (233 boys, 389 girls), their mothers (n = 535), and fathers (n =
      296) participated in the study. Results revealed that parents' self-evaluations
      explained additional variance in children's school adjustment, over and beyond
      the contribution of children's evaluation of their parents. Maternal reports on
      their positive behaviors (autonomy support, involvement, and structure) predicted
      their child's academic and emotional adjustment while their reported control
      predicted lower levels of these. Fathers' self-reported positive behaviors
      predicted academic adjustment while their control predicted lower academic and
      personal-emotional adjustment. These findings support the importance of multiple
      assessments of parental behaviors for improving the prediction of adjustment in
      school.

PMID- 27871017
TI  - Predicting postoperative gait in cerebral palsy.
AB  - In this work, postoperative lower limb kinematics are predicted with respect to
      preoperative kinematics, physical examination and surgery data. Data of 115
      children with cerebral palsy that have undergone single-event multilevel surgery
      were considered. Preoperative data dimension was reduced utilizing principal
      component analysis. Then, multiple linear regressions with 80% confidence
      intervals were performed between postoperative kinematics and bilateral
      preoperative kinematics, 36 physical examination variables and combinations of 9
      different surgical procedures. The mean prediction errors on test vary from 4
      degrees  (pelvic obliquity and hip adduction) to 10 degrees  (hip rotation and
      foot progression), depending on the kinematic angle. The unilateral mean sizes of
      the confidence intervals vary from 5 degrees  to 15 degrees . Frontal plane
      angles are predicted with the lowest errors, however the same performance is
      achieved when considering the postoperative average signals. Sagittal plane
      angles are better predicted than transverse plane angles, with statistical
      differences with respect to the average postoperative kinematics for both plane's
      angles except for ankle dorsiflexion. The mean prediction errors are smaller than
      the variability of gait parameters in cerebral palsy. The performance of the
      system is independent of the preoperative state severity of the patient. Even if
      the system is not yet accurate enough to define a surgery plan, it shows an
      unbiased estimation of the most likely outcome, which can be useful for both the
      clinician and the patient. More patients' data are necessary for improving the
      precision of the model in order to predict the kinematic outcome of a large
      number of possible surgeries and gait patterns.

PMID- 27871018
TI  - Is lower peripheral information weighted differently as a function of step number
      during step climbing?
AB  - The importance of peripheral visual information during stair climbing and how
      peripheral visual information is weighted as a function of step number during
      step climbing is unclear. Previous authors postulated that the knowledge of
      predictable characteristics of the steps may decrease reliance on foveal vision
      and transfer the online visual guidance of stair climbing to peripheral vision.
      Hence the aim of this study was to investigate if and how the occlusion of the
      lower peripheral visual field influenced stair climbing and if peripheral visual
      information was weighted differently between steps. Ten young adult male
      participants ascended a 5-step staircase under 2 visual conditions: full vision
      (FV) and lower visual occlusion (LO). Kinematic data (100Hz) were collected. The
      effect of Vision and Step condition on vertical forefoot clearance was examined
      with a Repeated Measures 2-way ANOVA. Tukey's HSD test was used for post-hoc
      comparisons. A significant interaction Vision x Step and main effect of Step were
      found (p<=0.04): vertical forefoot clearance was greater in LO compared to FV
      condition only on the 1st and the 2nd steps (p<0.013) and on the last step
      compared to the other steps (p<0.01). These findings suggest that online
      peripheral visual information is more relevant when negotiating the first two
      steps, rather than the end of a staircase and that the steps subsequent the first
      few ones may require different information likely based on proprioception or
      working memory of the step height.

PMID- 27871019
TI  - Comparison of lower limb and trunk kinematics between markerless and marker-based
      motion capture systems.
AB  - : Three dimensional (3-D) motion capture systems are used by researchers and
      clinicians to analyze the kinematics of human movement. Traditional marker based
      systems are time consuming and limit the size of studies. Markerless 3-D systems
      are quicker to use but the differences between data captured in each system is
      unclear. AIM: To examine the relationship of kinematic data captured by marker
      based and markerless motion capture systems. METHODS: Movement was assessed in
      two tests: a simple knee flexion test and single leg squat with a marker based
      protocol (Vicon) and a markerless protocol (Organic Motion). RESULTS: There was
      no significant difference between protocols in knee flexion angle (p=0.33). In
      single leg squat there was no significant difference in 9 of 13 clinically
      relevant joint angles in the change in angle from the start to the peak of squat.
      There were significant differences in the angle at the peak of the squat for 9 of
      13 joint angles. DISCUSSION: This study provides evidence that a marker-based and
      a markerless protocol report similar ranges of change in angle from the start of
      a squat to peak squat in the pelvis and lower limb in single leg squat. Specific
      joint angles should not be compared between protocols.

PMID- 27871020
TI  - Altered functional connectivity of interoception in illness anxiety disorder.
AB  - Interoception collects all information coming from the body and is sustained by
      several brain areas such as insula and cingulate cortex. Here, we used resting
      state functional magnetic resonance imaging to investigate functional
      connectivity (FC) of networks implied in interoception in patients with Illness
      anxiety disorders (IADs). We observed significantly reduced FC between the left
      extrastriate body area (EBA) and the paracentral lobule compared to healthy
      controls. Moreover, the correlation analysis between behavioural questionnaires
      and ROI to ROI FC showed that higher levels of illness anxiety were related to
      hyper-connectivity between EBA and amygdala and hippocampus. Scores on a
      questionnaire for interoceptive awareness were significantly correlated with
      higher FC between right hippocampus and nucleus accumbens bilaterally, and with
      higher connectivity between left anterior cingulate cortex (ACC) and left
      orbitofrontal cortex (OFC). Last, patients showed increased interoceptive
      awareness, measured by Self-Awareness Questionnaire (SAQ), and reduced capability
      in recognizing emotions, indicating inverse correlation between interoception and
      emotional awareness. Taken together our results suggested that, in absence of
      structural and micro-structural changes, patients with IADs show functional
      alteration in the neural network involved in the self-body representation; such
      functional alteration might be the target of possible treatments.

PMID- 27871021
TI  - Stop codons in the hepatitis B surface proteins are enriched during antiviral
      therapy and are associated with host cell apoptosis.
AB  - Premature stop codons in the hepatitis B virus (HBV) surface protein can be
      associated with nucleos(t)ide analogue resistance due to overlap of the HBV
      surface and polymerase genes. The aim of this study was to determine the effect
      of the replication of three common surface stop codon variants on the hepatocyte.
      Cell lines were transfected with infectious HBV clones encoding surface stop
      codons rtM204I/sW196*, rtA181T/sW172*, rtV191I/sW182*, and a panel of
      substitutions in the surface proteins. HBsAg was measured by Western blotting.
      Proliferation and apoptosis were measured using flow cytometry. All three surface
      stop codon variants were defective in HBsAg secretion. Cells transfected with
      these variants were less proliferative and had higher levels of apoptosis than
      those transfected with variants that did not encode surface stop codons. The most
      cytopathic variant was rtM204I/sW196*. Replication of HBV encoding surface stop
      codons was toxic to the cell and promoted apoptosis, exacerbating disease
      progression.

PMID- 27871022
TI  - Vascular-targeted photodynamic therapy of gastric antral vascular ectasia (GAVE).
AB  - BACKGROUND AND STUDY AIM: Vascular-targeted photodynamic therapy (V-PDT) has been
      used for several benign vascular diseases. The aim of this pilot study was to
      demonstrate the potential benefits of VPDT in the treatment of gastric antral
      vascular ectasia (GAVE). PATIENTS AND METHODS: Data from patients with GAVE (n=5)
      who underwent endoscopic V-PDT were analyzed retrospectively. Pre- and post-V-PDT
      clinical and endoscopic features, hemoglobin levels, and transfusion requirement
      were compared. RESULTS: The five GAVE patients received one to four sessions of V
      PDT. The hemoglobin levels of all five patients increased steadily following V
      PDT. Within 6-48months of follow-up, gastrointestinal bleeding and melena
      disappeared in all five patients and none of the patients needed a transfusion.
      Endoscopy examinations showed that the dilated vessels had disappeared without
      scar formation. No significant side effects or adverse reactions were reported.
      CONCLUSION: This preliminary study indicates the good selectivity, safety, and
      efficacy of V-PDT in the treatment of patients with GAVE. Larger prospective
      studies are needed to further confirm the feasibility of using V-PDT to treat
      patients with GAVE.

PMID- 27871024
TI  - Is it time to address survivorship in advanced breast cancer? A review article.
AB  - The outcome of advanced breast cancer has significantly improved over recent
      decades. As a consequence, the complex needs of patients living with the disease
      and their care-givers should be addressed not only in terms of supportive and
      palliative care but also of "survivorship" requirements. The multidisciplinary
      approach to advanced breast cancer should encompass - early in the history of the
      disease - not only physical but also functional, social, psychological and
      spiritual domains. It is important to clearly define the disease context with
      patients and families ("chronic" preferred to "incurable"), addressing the
      concept of uncertainty, and tailoring the treatment strategy according to both
      disease status and individual priorities. Specific psychosocial needs of young
      and elderly women and male patients - i.e. social security, job flexibility,
      rehabilitation (including sexuality), home and child care - should be recognized
      and supported. This review will address the key questions associated with
      survivorship in this disease context, recognizing the dearth of specific data and
      the urgent need for targeted clinical research and tailored interventions.

PMID- 27871023
TI  - Association of a novel GABRG2 splicing variation and a PTGS2/COX-2 single
      nucleotide polymorphism with Taiwanese febrile seizures.
AB  - Febrile seizure (FS) is the most common type of convulsion in infants and young
      children. The occurrence of FS in a subset of children with febrile illness
      suggested genetic factors may have an important effect on the predisposition of
      the disease. Using targeted next generation sequencing (NGS), a novel splicing
      variation (NM_198903.2:c.1249-1G>T) was identified in the gamma-aminobutyric acid
      type A (GABA-A) receptor gamma2 subunit (GABRG2) gene of a FS patient. To
      investigate possible association of FS with single nucleotide polymorphisms
      (SNPs) in prostaglandin-endoperoxide synthase-2 (prostaglandin G/H synthase-2;
      PTGS2/cyclooxygenase-2; COX2) gene involving in thermoregulatory pathway, eight
      SNPs, rs689465, rs689466, rs20417, rs13306038, rs201931599, rs689470, rs4648306
      and rs4648308, along with 2 previously reported variations in IL1RN (86-bp VNTR)
      and IL10 (rs1900872) were genotyped and utilized for case-control association
      studies on 35 FS and 31 non-FS controls. A single SNP (rs689466) localized at 5'
      1192 of the PTGS2 gene exhibited significant association with FS (p=0.045) based
      on case-control allelic association analyses. A significant decrease in the
      frequency of the G allele in FS (0.357) was observed compared to that in controls
      (0.536) with an estimated odds ratio (OR) of 0.48 (95% CI, 0.23-0.99) for the G
      versus A allele. Using case-control genotypic association analysis, the -1192 A
      allele is most likely to confer susceptibility to FS by a recessive action model
      (p=0.045, pointwise empirical p value (EMP1)=0.049). The association of SNPs in
      PTGS2, in addition to IL6, IL-6 receptor (IL6R) and prostaglandin E receptor 3
      (PTGER3) in prior reports, with FS suggests their possible action in concert to
      modulate phenotypes in FS as well as the involvement of thermoregulatory pathway
      in pathogenesis of FS.

PMID- 27871025
TI  - Factors influencing local control in patients undergoing breast conservation
      surgery for ductal carcinoma in situ.
AB  - BACKGROUND: The aim of our study was to assess various predictors for local
      recurrence (LR) in patients undergoing breast conservation surgery (BCS) for
      ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: An audit was performed of
      582 consecutive patients with DCIS between Jan 1975 to June 2008. In patients
      undergoing BCS, local guidelines reported a margin of >=10 mm during the above
      period. Guideline with regard to margin of excision changes soon after this
      period. We retrospectively analysed clinical and pathological risk factors for
      local recurrence in patients undergoing BCS. Statistical analysis was carried out
      using SPSS version 19, and a cox regression model for multivariate analysis of
      local recurrence was used. RESULTS: Overall 239 women had BCS for DCIS during the
      above period. The actuarial 5-year recurrence rate was 9.6%. The overall LR rate
      was 17% (40/239. LR was more common in patients <=50 years: (10/31 patients, 32%)
      compared to patients > 50 years (30/208, 14%, P = 0.02). Forty three per cent of
      patients (6/14) with <5 mm margin developed LR which was significantly higher
      compared to patients with 5-9 mm margin (12%, 3/25) and with >=10 mm margin (14%,
      27/188, P = 0.01). On multivariate analysis age <=50 years, <5 mm pathological
      margin were independent prognostic factors for local recurrence. CONCLUSION: Our
      study shows that younger age (<=50 years) and a margin < 5 mm are poor prognostic
      factors for LR in patients undergoing breast conservation surgery for DCIS.

PMID- 27871026
TI  - Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic
      symptoms?
AB  - Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose
      dependently provokes panic anxiety in man, accompanied by adrenocorticotropic
      hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral
      and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone
      (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was
      shown to increase as well vasopressin (AVP), which acts synergistically with CRH
      as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C
      terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is
      more stable in the circulation and easier to determine than AVP and it was found
      to closely mirror the production of AVP. So far, CoP secretion has not been
      characterized during panic provocation. In 30 healthy male human subjects, we
      repeatedly measured CoP in plasma during a panic challenge and studied its
      correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol.
      CoP levels correlated positively with the increase in API ratings (r=0.41,
      p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53,
      respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009)
      and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As
      expected, we found a positive correlation between plasma ACTH and cortisol levels
      (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was
      demonstrated, which was correlated positively to panic symptoms and pituitary
      adrenocortical release. Our findings suggest a role of CoP as a potential
      surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate
      our results and to further clarify the role of CoP as a stress-sensitive hormone
      in different panic paradigms as well as in panic patients.

PMID- 27871027
TI  - Trauma exposure relates to heightened stress, altered amygdala morphology and
      deficient extinction learning: Implications for psychopathology.
AB  - Stress exposure causes a structural reorganization in neurons of the amygdala. In
      particular, animal models have repeatedly shown that both acute and chronic
      stress induce neuronal hypertrophy and volumetric increase in the lateral and
      basolateral nuclei of amygdala. These effects are visible on the behavioral
      level, where stress enhances anxiety behaviors and provokes greater fear
      learning. We assessed stress and anxiety levels in a group of 18 healthy human
      trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls
      (HC group), and related these measurements to amygdala volume. Traumas included
      unexpected adverse experiences such as vehicle accidents or sudden loss of a
      loved one. As a measure of aversive learning, we implemented a cued fear
      conditioning paradigm. Additionally, to provide a biological marker of chronic
      stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA)
      axis using a dexamethasone suppression test. Compared to the HC, the TR group
      showed significantly higher levels of chronic stress, current stress and trait
      anxiety, as well as increased volume of the left amygdala. Specifically, we
      observed a focal enlargement in its lateral portion, in line with previous animal
      data. Compared to HC, the TR group also showed enhanced late acquisition of
      conditioned fear and deficient extinction learning, as well as salivary cortisol
      hypo-suppression to dexamethasone. Left amygdala volumes positively correlated
      with suppressed morning salivary cortisol. Our results indicate differences in
      trauma-exposed individuals which resemble those previously reported in animals
      exposed to stress and in patients with post-traumatic stress disorder and
      depression. These data provide new insights into the mechanisms through which
      traumatic stress might prompt vulnerability for psychopathology.

PMID- 27871028
TI  - Microstructure analysis method for evaluating degenerated intervertebral disc
      tissue.
AB  - Degeneration of intervertebral disc (IVD) tissue is characterized by several
      structural changes that result in variations in disc physiology and loss of
      biomechanical function. The complex process of degeneration exhibits highly
      intercorrelated biomechanical, biochemical, and cellular interactions. There is
      currently some understanding of the cellular changes in degenerated
      intervertebral disc tissue, but microstructural changes and deterioration of the
      tissue matrix has previously been rarely explored. In this work, sequestered IVD
      tissue was successfully characterized using histology, light microscopy, and
      scanning electron microscopy (SEM) to quantitatively evaluate parameters of
      interest for intervertebral disc degeneration (IDD) such as delamination of the
      collagenous matrix, cell density, cell size, and extra cellular matrix (ECM)
      thickness. Additional qualitative parameters investigated included matrix
      fibration and irregularity, neovascularization of the IVD, granular inclusions in
      the matrix, and cell cluster formation. The results of this study corroborated
      several previously published findings, including those positively correlating
      female gender and IVD cell density, age and cell size, and female gender and ECM
      thickness. Additionally, an array of quantitative and qualitative investigations
      of IVD degeneration could be successfully evaluated using the given methodology,
      resin-embedded SEM in particular. SEM is especially practical for studying
      micromorphological changes in tissue, as other microscopy methods can cause
      artificial tissue damage due to the preparation method. Investigation of the
      microstructural changes occurring in degenerated tissue provides a greater
      understanding of the complex process of disc degeneration as a whole. Developing
      a more complete picture of the degenerative changes taking place in the
      intervertebral disc is crucial for the advancement and application of
      regenerative therapies based on the pathology of intervertebral disc
      degeneration.

PMID- 27871029
TI  - Effects of cerebrolysin on functional recovery in patients with severe disability
      after traumatic brain injury: A historical cohort study.
AB  - OBJECTIVE: To determine the effects of cerebrolysin on functional recovery in
      patients with severe disability after traumatic brain injury (TBI). METHODS: This
      was a retrospective cohort study being performed during a 2-year period in a
      level I trauma center in Southern Iran including all the adult patients
      (>16years) with severe disability (GOS of 2 and 3) 1-month after trauma. We
      excluded those with posttraumatic seizures and those with meningitis or current
      infections. Some patients received cerebrolysin (n=65) and some did not (n=64).
      Cerebrolysin was administered intravenously in 10mL dosage daily for 30days.
      Patients in two study groups were matched regarding the baseline characteristics
      including age, gender, GCS on admission, pupil reactivity and Rotterdam score.
      The administered cerebrolysin dosage was 10mL intravenously daily for 30days. The
      3- and 6-month Glasgow Outcome Scale Extended (GOSE) was recorded. The outcome
      scales were compared between two study groups. RESULTS: Overall we included 129
      patients with severe disability 1-month after TBI. The baseline characteristics
      were comparable between groups. We found that GOSE at 3-month (p=0.017) and 6
      month (p=0.009) was significantly higher in those receiving cerebrolysin.
      Cerebrolysin administration was associated with lower mortality rate, and higher
      good recovery after 6 month of therapy (p=0.024). Cerebrolysin administration was
      also associated with higher favorable and lower unfavorable outcome (p=0.043).
      Cerebrolysin was associated with higher seizure rate (p=0.042). CONCLUSION:
      Cerebrolysin administration in patients with severe disability after TBI is
      associated with improved functional recovery, decreased mortality rate and
      increased favorable outcome. Seizure is important side effect of cerebrolysin
      administration in TBI patients.

PMID- 27871031
TI  - Prominent increased calcineurin immunoreactivity in the superior temporal gyrus
      in schizophrenia: A postmortem study.
AB  - Many neuroimaging studies have demonstrated structural changes in the superior
      temporal gyrus (STG) in patients with schizophrenia. Several postmortem studies
      have reported on the pathogenesis of schizophrenia, but few reports have
      investigated alterations in molecules in the STG. In addition, several studies
      have suggested that calcineurin (CaN) inadequacy may be a risk factor for
      schizophrenia, but no reports about CaN expression in the STG in schizophrenia
      have been published. We compared the density of CaN-immunoreactive (CaN-IR)
      neurons in the STG from 11 patients with schizophrenia with that of 11 sex- and
      age-matched controls. We used immunohistochemical analysis with rabbit polyclonal
      antibodies against human CaN. In the STG, the density of CaN-IR neurons in layers
      II - VI in the group with schizophrenia was significantly higher than that in the
      control group. Our results confirmed pathological changes in the STG in patients
      with schizophrenia, suggesting that alterations in the CaN pathway play a role in
      the pathogenesis of schizophrenia.

PMID- 27871030
TI  - The impact of gender on treatment effectiveness of body psychotherapy for
      negative symptoms of schizophrenia: A secondary analysis of the NESS trial data.
AB  - Despite promising findings from small-scale studies suggesting that body
      psychotherapy may be an effective treatment for negative symptoms, these results
      were not replicated in a recent multisite trial. In this trial a far smaller
      proportion of women were recruited relative to earlier studies, which may be an
      issue given the gender mix of the sample evaluated has been found to affect trial
      outcomes in schizophrenia. Using data from our multisite trial, the interaction
      between gender and treatment allocation as a predictor of outcomes was examined
      in 275 participants (72 women and 203 men) randomised to either a body
      psychotherapy or Pilates group. Negative symptoms were found to significantly
      reduce in women randomised to the body psychotherapy condition in comparison to
      Pilates, while no such effect was detected in men. Consistent with the smaller
      trials, this improvement was found to relate predominantly to expressive
      deficits. These findings suggest that body psychotherapy may be an effective
      treatment for negative symptoms in women. These findings emphasise the importance
      of sample characteristics in determining trial outcome in psychological treatment
      studies.

PMID- 27871032
TI  - Level of serum thioredoxin and correlation with neurocognitive functions in
      patients with schizophrenia using clozapine and other atypical antipsychotics.
AB  - Thioredoxin is a serum antioxidant that has been investigated in the etiology of
      schizophrenia. The aim of this study is investigating the relationship between
      serum thioredoxin levels and cognitive functions in acute psychotic episode and
      remission state patients with schizophrenia; and examining whether there were
      differences between patients using clozapine and other atypical antipsychotics;
      including risperidone, olanzapine and amisulpride. This research was performed in
      schizophrenia patients hospitalized with acute psychotic episode (n=57),
      reevaluated patients after the initiation of treatment (mean 16 weeks) (n=46),
      and healthy controls (n=41). Positive and Negative Syndrome Scale, Clinic Global
      Impressions Scale, Neuropsychologic test battery to assess cognitive performance,
      and serum thioredoxin levels measured by ELISA were used in this research. Serum
      thioredoxin levels were highest in acute psychotic episode, lower in the
      remission state and the lowest in healthy controls. Significant correlation has
      been established between serum thioredoxin levels and Trail Making Test-A
      performance in remission state patients. In conclusion, serum thioredoxin levels
      were increased in acute psychotic episode and decreased in remission state, and
      its relationship with attention is worth to consider in schizophrenia patients.

PMID- 27871033
TI  - Design, synthesis, anticancer, antimicrobial activities and molecular docking
      studies of novel quinoline bearing dihydropyridines.
AB  - A new series of eight quinoline bearing dihydropyridine derivatives (A1-A8) were
      synthesized in high yield and in short reaction time by a four component reaction
      of 2-chloro-3-fomyl quinoline, malononitrile, arylamines and dimethyl
      acetylenedicarboxylate in the presence of a catalytic amount of triethylamine.
      The compounds were fully characterized by IR, NMR and GC-MS. These compounds were
      screened for potential biological activity in an A549 lung cancer cell line and
      were also evaluated for their antibacterial activities against Pseudomonas
      aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC
      29213 whilst their molecular docking properties in an enzymatic system were also
      determined. Compounds A2, A3, A4 and A8 showed anti-proliferative activity; with
      A4 having the highest toxicity at 250MUg/mL and A8 has high toxicity at 125, 250
      and 500MUg/mL, respectively. Antibacterial results indicated that A4 have
      significant activity against tested microorganisms at the minimum inhibitory
      concentration (MIC) values of 32MUg/mL against Pseudomonas aeruginosa and
      Escherichia coli, and 16MUg/mL against Staphylococcus aureus. Docking of A1 with
      human mdm2 indicated the lowest binding energy (-6.111Kcal/mol) thereby showing
      strong affinity of the ligand molecule with the receptor which has been
      stabilized by strong hydrogen bond interactions in the binding pocket. This
      confirms that A1 is a better inhibitor for E3 ubiquitin-protein ligase mdm2.

PMID- 27871034
TI  - Isotope fractionation of benzene during partitioning - Revisited.
AB  - Isotope fractionation between benzene-D0 and benzene-D6 caused by multi-step
      partitioning of the benzenes between water and two organic solvents, n-octane and
      1-octanol, as well as between water and the gas phase, was measured. The obtained
      fractionation factors alphaH = KH/KD are alphaH = 1.080 +/- 0.015 and alphaH =
      1.074 +/- 0.015 for extraction into n-octane and 1-octanol, respectively, and
      alphaH = 1.049 +/- 0.010 for evaporation from aqueous solution. The comparison of
      solvent- and gas-phase partitioning reveals that about 2/3 of the driving force
      of fractionation is due to different interactions in the aqueous phase, whereas
      1/3 is due to different interactions in the organic phase. The heavy benzene
      isotopologue behaves more 'hydrophilically' and the light one more
      'hydrophobically'. This synergistic alignment gives rise to relatively large
      fractionation effects in partitioning between water and non-polar organic matter.
      In contrast to a previous study, there is no indication of strong fractionation
      by specific interactions between benzene and octanol. Partitioning under non
      equilibrium conditions yields smaller apparent fractionation effects due to
      opposite trends of thermodynamic and kinetic fractionation parameters, i.e.
      partition and diffusion coefficients of the isotopologues. This may have
      consequences which should be taken into account when considering isotope
      fractionation due to sorption in environmental compartments.

PMID- 27871035
TI  - Analyzing pH-induced changes in a myofibril model system with vibrational and
      fluorescence spectroscopy.
AB  - The decline of pH and ultimate pH in meat postmortem greatly influences meat
      quality (e.g. water holding capacity). Four spectroscopic techniques, Raman,
      Fourier transform infrared (FT-IR), near infrared (NIR) and fluorescence
      spectroscopy, were used to study protein and amino acid modifications to
      determine pH-related changes in pork myofibril extracts at three different pH
      levels, 5.3, 5.8 and 6.3. Protonation of side-chain carboxylic acids of aspartic
      and glutamic acid and changes in secondary structure, mainly the amide I-III
      peaks, were the most important features identified by Raman and FT-IR
      spectroscopy linked to changes in pH. Fluorescence spectroscopy identified
      tryptophan interaction with the molecular environment as the most important
      contributor to changes in the spectra. NIR spectroscopy gave no significant
      contributions to interpreting protein structure related to pH. Results from our
      study are useful for interpreting spectroscopic data from meat where pH is an
      important variable.

PMID- 27871036
TI  - Influence of red wine pomace seasoning and high-oxygen atmosphere storage on
      carcinogens formation in barbecued beef patties.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAs)
      are carcinogenic compounds formed in barbecued meat. Conditions that reduce their
      formation are of major interest. This study aims to evaluate the influence of red
      wine pomace seasoning (RWPS) and high-oxygen atmosphere storage on the formation
      of PAHs and HAs in barbecued beef patties. In general, the levels of PAHs and HAs
      quantified were low. The storage (9days) promoted higher formation of PAHs in
      control patties without increase of HAs. RWPS patties cooked at preparation day
      presented higher levels of PAHs and HAs than control. Nevertheless, RWPS patties
      cooked after storage presented lower levels of PAHs and HAs than control. ABTS
      assay pointed out that higher radical scavenging activity may be related to with
      lower PAHs or HAs formation. In conclusion, RWPS can be an interesting ingredient
      to inhibit the formation of cooking carcinogens in barbecued patties stored at
      high-oxygen atmosphere.

PMID- 27871037
TI  - Design, synthesis and SAR analysis of potent BACE1 inhibitors: Possible lead drug
      candidates for Alzheimer's disease.
AB  - We have identified potent isophthalic acid derivatives armed with imidazol and
      indolyl groups as potent beta-secretase inhibitors. The most effective analogs
      demonstrated low nano-molar potency for the BACE1 (beta-secretase cleaving
      enzyme) as measured by FRET (Fluorescence Resonance Energy Transfer) and cell
      based (ELISA) assays. Our design strategy followed a traditional SAR approach and
      was supported by molecular modeling studies based on previously reported
      hydroxyethylene transition state inhibitor derived from isophthalic acid I. In
      the FRET assay, the most potent compound, 10a, displayed an IC50 value for BACE1
      of 75 nM, and exhibited cellular activity with an EC50 value of 0.81 MUM. On the
      other hand, compound 11b was found to be the most potent compound in the cell
      based assay with an EC50 value of 0.29 MUM.

PMID- 27871038
TI  - Imidazopyridine-fused [1,3]-diazepinones part 2: Structure-activity relationships
      and antiproliferative activity against melanoma cells.
AB  - We recently described a pyrido-imidazodiazepinone derivative which could be a
      promising hit compound for the development of new drugs acting against melanoma
      cells. In this study, a series of 28 novel pyrido-imidazodiazepinones were
      synthesized and screened for their in vitro cytotoxic activities against the
      melanoma MDA-MB-435 cell line. Among the derivatives, seven of them showed 50%
      growth inhibitory activity at 1 MUM concentration, and high selectivity against
      the melanoma cell line MDA-MB-435.

PMID- 27871039
TI  - Synthesis and antitumor activity of novel substituted uracil-1'(N)-acetic acid
      ester derivatives of 20(S)-camptothecins.
AB  - A series of novel substituted uracil-1'(N)-acetic acid esters (6-20) of
      camptothecins (CPTs) were synthesized by the acylation method. These new
      compounds were evaluated for in vitro antitumor activity against tumor cell
      lines, A549, Bel7402, BGC-823, HCT-8 and A2780. In vitro results showed that most
      of the derivatives exhibited comparable or superior cytotoxicity compare to CPT
      (1) and topotecan (TPT, 2), with 12 and 13 possessing the best efficacy. Four
      compounds, 9, 12, 13 and 16, were selected to be evaluated for in vivo antitumor
      activity against H22, BGC-823 and Bel-7402 in mice. In vivo testing results
      indicated that 12 and 13 had antitumor activity against mouse liver carcinoma H22
      close to Paclitaxel and cyclophosphamide. 12 had similar antitumor activity
      against human gastric carcinoma BGC-823 in nude mice compared to irinotecan (3)
      and possessed better antitumor activity against human hepatocarcinoma Bel-7402 in
      nude mice than 2. It is also discovered that 12 showed a similar mechanism but
      better inhibitory activity on topoisomerase I (Topo I) compared to 2. These
      findings indicate that 20(S)-O-fluorouracil-1'(N)-acetic acid ester derivative of
      CPTs, 12, could be developed as an antitumor drug candidate for clinical trial.

PMID- 27871040
TI  - Mobile technology in clinical teaching.
AB  - Technology is having a profound effect on education in the 21st century and nurse
      educators are being challenged to integrate technological innovation to assist
      students in their learning. This paper reports a study on the introduction of
      smart mobile technology to support student learning in the clinical environment.
      In a climate of collaborative inquiry, clinical lecturers and two researchers
      from the same department carried out a project in three phases: formation,
      implementation and analysis. Following the formation phase, six clinical
      lecturers adopted iPads to support their clinical teaching (implementation
      phase). At this time they also kept reflective journals. In the analysis phase a
      thematic analysis of the data from the journals and from a focus group found both
      enabling and constraining factors influenced the use of iPads by clinical
      lecturers. The themes categorised as enablers were: resources and technology;
      and, management and technology support. Those identified as barriers or
      constraining factors were: clinical staff engagement; and lecturer experience
      with technology. Student engagement and learning, and connectivity were both
      enabling and constraining factors. This paper concludes that the use of a mobile
      device such as an iPad can enhance teaching in clinical settings but that in
      order for such devices to be successfully integrated into clinical teaching
      consideration needs to be given to professional development needs, adequate
      resourcing and technology support.

PMID- 27871041
TI  - Toxicity of aqueous vanadium to zooplankton and phytoplankton species of
      relevance to the athabasca oil sands region.
AB  - Vanadium (V) is an abundant trace metal present in bitumen from the Athabasca Oil
      Sands (AOS) region in Alberta, Canada. The upgrading of bitumen can result in the
      production of large volumes of a carbonaceous material referred to as petroleum
      coke that contains V at elevated levels compared to the native bitumen. Previous
      studies have shown that coke has the capacity to leach ecotoxicologically
      relevant levels of V into water it contacts, yet limited data are available on
      the toxicity of aqueous V to planktonic organisms. Therefore, this study set out
      to evaluate the acute and chronic toxicity of V (as vanadate oxyanions) to
      freshwater zooplankton and phytoplankton species that are either commonly-used
      laboratory species, or species more regionally-representative of northern
      Alberta. Four cladoceran (2-d and 21-d tests) and two algal (3-d tests) species
      were exposed to V to obtain both acute and chronic toxicity estimates. Acute V
      toxicity (LC50s) ranged from 0.60mgV/L for Ceriodaphnia quadrangula to 2.17mgV/L
      for Daphnia pulex. Chronic toxicity estimates (EC50s) for cladoceran survival and
      reproduction were nearly identical within species and ranged from a low of 0.13
      to a high of 0.46mgV/L for Daphnia dentifera and D. pulex, respectively. The lack
      of sublethal V toxicity in daphnia suggests a direct mechanism of toxicity
      through ion imbalance. Growth inhibition (EC50) of green algae occurred at
      concentrations of 3.24 and 4.12mgV/L for Pseudokirchneriella subcapitata and
      Scenedesmus quadricauda, respectively. Overall, cladocerans were more sensitive
      to V than green algae, with survival of the field-collected D. dentifera being
      approximately 2.5 to 3.5 times more sensitive to acute and chronic V exposure
      than the standard test species D. pulex. However, there were no significant
      differences in V toxicity between the field-collected cladocerans Simocephalus
      serrulatus and C. quadrangula, compared to the respective standard species D.
      pulex and Ceriodaphnia dubia. Similarly, there were no significant differences in
      sensitivity to V in the two algal species evaluated. Based on V concentrations
      reported in laboratory-generated coke leachates, zooplankton survival could be
      adversely impacted under conditions of chronic leachate exposure if V
      concentrations in the environment exceed 0.1mg/L. Furthermore, toxicity
      thresholds from commonly-used planktonic test species would likely have sufficed
      for derivation of a V water quality guideline (WQG) for protection of local
      aquatic communities near oil sands operations, but the new data presented here on
      V toxicity to more regionally-representative species will strengthen the database
      for WQG derivation.

PMID- 27871042
TI  - Is trade liberalisation a vector for the spread of sugar-sweetened beverages? A
      cross-national longitudinal analysis of 44 low- and middle-income countries.
AB  - Does trade and investment liberalisation increase the growth in sales of sugar
      sweetened beverages (SSBs)? Here, for the first time to our knowledge, we test
      this hypothesis using a unique data source on SSB-specific trade flows. We test
      whether lower tariffs effectively increase imports of SSBs, and whether a higher
      level of imports increase sales of SSBs. Cross-national fixed effects models were
      used to evaluate the association between SSBs sales and trade liberalisation.
      SSBs per capita sales data were taken from EuroMonitor, covering 44 low- and
      middle-income countries from 2001 to 2014, SSBs import data were from TradeMap,
      Foreign Direct Investment data were from EuroMonitor, and data on applied tariffs
      on SSB from the World Trade Organisation tariffs database, all 2015 editions. The
      results show that higher tariffs on SSBs significantly decreased per capita SSB
      imports. Each one percent increase in tariffs was associated with a 2.9% (95% CI:
      0.9%-5%) decrease in imports of SSBs. In turn, increased imports of SSBs were
      significantly associated with greater sales of SSBs per capita, with each 10
      percent increase in imports (in US$) associated with a rise in sales of 0.36 L
      per person (95% CI: 0.08-0.68). Between 2001 and 2014, this amounted to 9.1 L
      greater sales per capita, about 40% of the overall rise seen in this period in
      LMICs. We observed that tariffs were inversely but not significantly associated
      with sales of SSBs. In conclusion, lower tariffs substantially increased imports
      of SSBs in LMICs, which translated into greater sales. These findings suggest
      that trade policies which lower tariff barriers to SSB imports can be expected to
      lead to increased imports and then increased sales of SSBs in LMICs, with adverse
      consequences for obesity and the diseases that result from it.

PMID- 27871043
TI  - Evaluating the perceived effectiveness of pregnancy-related cigarette package
      health warning labels among different gender/age groups.
AB  - INTRODUCTION: The impact of pregnancy-related health warning labels (HWLs)
      appearing on cigarette packages on women of reproductive age and other socio
      demographic groups is not well understood. The current study analyzes how
      different age/gender groups respond to pregnancy-related HWLs as compared to non
      pregnancy HWLs. METHODS: Data were analyzed from four waves of an online
      longitudinal study with adult smokers aged 18-64 in Australia, Canada, Mexico,
      and the US. Participants were classified into four age?gender groups: women 40
      and under; men 40 and under; women over 40; men over 40. Participants rated one
      pregnancy-related and several non-pregnancy related labels on worry,
      believability, and motivation to quit. Country-specific adjusted linear GEE were
      estimated regressing ratings for each of the three key outcomes for 1) pregnancy
      related HWLs and 2) a rating difference score that subtracted the average ratings
      of the non-pregnancy warning from the rating of the pregnancy warning. All models
      adjusted for socio-demographics and smoking related variables. RESULTS: In Mexico
      and Australia, where graphic pregnancy-related HWL imagery is used (i.e.,
      premature infant), women of reproductive age reported stronger believability,
      worry, and quit motivation than all other groups. Results were similar in the US,
      where text only HWLs are used. In contrast in Canada, where the pregnancy-related
      HWL imagery features a pregnant woman, ratings were unassociated with gender/age
      groups. Stronger effects among women of reproductive age were limited to
      pregnancy HWLs in each country, except Canada. CONCLUSIONS: HWLs that depict
      graphic effects to illustrate smoking-related pregnancy risks appear to be
      perceived as particularly effective among women of reproductive age.

PMID- 27871044
TI  - Now is the time to advocate for interventions designed specifically to prevent
      and control waterpipe tobacco smoking.
AB  - Waterpipe tobacco usage is spreading rapidly worldwide, with reports of more
      youth being waterpipe users compared to adults. In many areas of the world,
      waterpipe usage surpasses cigarette smoking. Waterpipes and cigarettes are both
      mechanisms for inhalation of tobacco smoke and therefore have serious health
      consequences. However, because of the many differences between the two products,
      prevention and control strategies that have proven effective for cigarettes may
      not transfer readily to waterpipe. This report highlights the differences between
      waterpipes and cigarettes in toxicant exposure and physiologic effects, patterns
      of use, social norms, the extent of evidence, and the policy environment. There
      is little evidence to date around effective interventions for waterpipe
      prevention and control. The current state of evidence for intervention to curb or
      control waterpipe is at ground zero and critically needs attention from both
      scientists and policy makers. National and global efforts aimed at cigarette
      prevention have succeeded, particularly in developed countries. We suggest the
      time has come to harness what we know works for cigarette prevention and control
      and adapt it to tackle the growing epidemic of waterpipe tobacco use.

PMID- 27871045
TI  - Electronic cigarette and marijuana use among youth in the United States.
AB  - BACKGROUND: There are growing concerns over the high rate of electronic cigarette
      (e-cigarette) use and decreases in perceived harm of marijuana use among youth.
      We seek to identify risk factors associated with e-cigarette and marijuana use
      among U.S. middle and high school students. METHODS: Estimates of e-cigarette use
      only, marijuana use only, dual use of both substances as well as frequency of
      substance use were calculated for 8th, 10th and 12th grades with the typical age
      of 13, 15, 17 years old respectively by using the 2014 Monitoring the Future
      survey (n=16,184). RESULTS: Overall, 7.9% of students only used e-cigarettes,
      9.3% of students only used marijuana, and 6.6% of students used both e-cigarettes
      and marijuana in the last 30days. E-cigarette use only was most prevalent among
      8th and 10th graders while marijuana use only was most prevalent among 12th
      graders. The dual use of e-cigarettes and marijuana rapidly increased from 8th
      graders (2.6%) to 10th graders (7.3%) and maintained a high level for 12th
      graders (8.5%). Students' sociodemographic factors, school performance and work
      intensity were associated with e-cigarette and marijuana use in the multivariate
      analysis. Being a dual user of e-cigarettes and marijuana was associated with
      increased risk of a medium level or a high level of e-cigarette use and a medium
      level of marijuana use CONCLUSIONS: This study raised the possibility that youth
      start to use e-cigarettes at an earlier age and then progress to other
      substances. Education campaigns with tailored messages to prevent youth from
      vaping and drug use are critically needed.

PMID- 27871046
TI  - Recombinant azurin-CdSe/ZnS hybrid structures for nanoscale resistive random
      access memory device.
AB  - In the present study, we developed a biohybrid material composed of recombinant
      azurin and CdSe-ZnS quantum dot to perform as a resistive random access memory
      (ReRAM) device. Site specific amino acid sequences were introduced in azurin to
      bind with the surface of CdSe-ZnS nanoparticle allowing the formation of a hybrid
      and voltage-driven switching enabled to develop a resistive random access memory
      (ReRAM) device. The analytical measurements confirmed that the azurin and CdSe
      ZnS nanoparticles were well conjugated and formed into a single hybrid. Further,
      reversible, bistable switching along with repeatable writing-reading-erasing
      processes on individual azurin/CdSe-ZnS hybrid at nanoscale was achieved on the
      hybrid device. The device was programmed tested for 50 cycles with an ON/OFF
      ratio and measured to be of three orders of magnitude. The developed device shown
      good stability and repeatability and operates at low voltages thus makes it
      promising candidate for future memory device applications.

PMID- 27871047
TI  - A novel label-free electrochemical immunosensor based on functionalized nitrogen
      doped graphene quantum dots for carcinoembryonic antigen detection.
AB  - A novel and ultrasensitive label-free electrochemical immunosensor was fabricated
      for quantitative detection of carcino-embryonic antigen (CEA). The nitrogen-doped
      graphene quantum dots (N-GQDs) supported PtPd bimetallic nanoparticles (PtPd/N
      GQDs) were synthesized by a simple and green hydrothermal procedure.
      Subsequently, PtPd/N-GQDs functionalized Au nanoparticles (PtPd/N-GQDs@Au) were
      prepared successfully via a self-assembly approach. Because of the synergetic
      effect present in PtPd/N-GQDs@Au, this novel nanocomposites has shown excellent
      electrocatalytic activity towards hydrogen peroxide (H2O2) reduction. Featuring
      good biocompatibility, excellent conductivity and large surface area, PtPd/N
      GQDs@Au was applied as transducing materials to efficiently conjugate capture
      antibodies and amplify electrochemical signal. Under the optimal conditions, the
      proposed immunosensor was used for the detection of CEA with wide dynamic range
      in the range from 5 fg/mL to 50ng/mL with a low detection limit of 2fg/mL
      (S/N=3). Furthermore, this label-free immunosensor possesses high sensitivity,
      special selectivity and long-term stability, which shows promising application in
      bioassay analysis.

PMID- 27871048
TI  - Construction of a highly sensitive non-enzymatic sensor for superoxide anion
      radical detection from living cells.
AB  - A novel non-enzymatic superoxide anion (O2*-) sensor was fabricated based on Ag
      nanoparticles (NPs)/L-cysteine functioned carbon nanotubes (Cys-MWCNTs)
      nanocomposites and used to measure the release of O2*- from living cells. In this
      strategy, AgNPs could be uniformly electrodeposited on the MWCNTs surface with
      average diameter of about 20nm as exhibited by scanning electronmicroscopy (SEM).
      Electrochemical study demonstrated that the AgNPs/Cys-MWCNTs modified glassy
      carbon electrode exhibited excellent catalytic activity toward the reduction of
      O2*- with a super wide linear range from 7.00*10-11 to 7.41*10-5M and a low
      detection limit (LOD) of 2.33*10-11M (S/N=3). Meanwhile, the mechanism for O2*-
      reduction was also proposed for the first time. Importantly, this novel non
      enzymatic O2*- sensor can detect O2*- release from cancer cells under both the
      external stimulation and the normal condition, which has the great potential
      application in clinical diagnostics to assess oxidative stress of living cells.

PMID- 27871049
TI  - What kinds of alternative possibilities are required of the folk concept(s) of
      choice?
AB  - Our concept of choice is integral to the way we understand others and ourselves,
      especially when considering ourselves as free and responsible agents. Despite the
      importance of this concept, there has been little empirical work on it. In this
      paper we report four experiments that provide evidence for two concepts of choice
      namely, a concept of choice that is operative in the phrase having a choice and
      another that is operative in the phrase making a choice. The experiments indicate
      that the two concepts of choice can be differentiated from each other on the
      basis of the kind of alternatives to which each is sensitive. The results
      indicate that the folk concept of choice is more nuanced than has been assumed.
      This new, empirically informed understanding of the folk concept of choice has
      important implications for debates concerning free will, responsibility, and
      other debates spanning psychology and philosophy.

PMID- 27871050
TI  - Removal characteristics of DON in pharmaceutical wastewater and its influence on
      the N-nitrosodimethylamine formation potential and acute toxicity of DOM.
AB  - Previous research has focused on dissolved organic carbon (DOC) as a surrogate
      for dissolved organic matter (DOM) in pharmaceutical wastewater. Dissolved
      organic nitrogen (DON) as a part of DOM has received little attention. This study
      investigated the removal characteristics of DON and its influence on the N
      nitrosodimethylamine formation potential (NDMA FP) and acute toxicity of DOM in a
      full-scale hydrolysis/acidification + anaerobic/anoxic/aerobic + moving bed
      biofilm reactor (MBBR) process treating pharmaceutical wastewater. Results showed
      that maximum removal of DON (68 +/- 12%) was present in the anaerobic process.
      The removal of DON by anoxic and aerobic processes was negligible as a result of
      the production of new N-containing compounds that are characteristic of
      proteins/amino sugars and lipids. DON concentration decreased significantly in
      the MBBR process (p < 0.05, t-test), indicating that manipulation of the solids
      retention times (SRTs) could be a solution to minimize DON. Based on the Pearson
      correlation analysis, the behavior of NDMA FP and DOM acute toxicity was
      significantly associated with the 3 kDa < MW < 10 kDa (r = 0.709, p < 0.05) and
      MW < 3 kDa DON (r = 0.659, p < 0.05), respectively, and are not identical to that
      of DOC fractions (r = 0.037-0.466, p = 0.051-0.886). Moreover, the removal and
      molecular changes of DON are not coupled with that of DOC during biotreatment.
      Thus, testing the performance indicator of DON in pharmaceutical wastewater was
      recommended, as it provides important information for DOM removal
      characteristics.

PMID- 27871052
TI  - Crystallinity as a tunable switch of poly(L-lactide) shape memory effects.
AB  - Materials with shape memory effect (SME) have already been widely used in the
      medical field. The interesting part of this group is represented by double
      function materials. The bioresorption and SME ability are common in polyesters
      implants. The first information about vascular stent made of bioresorbable
      polyester with SME was published in 2000. However, there are not many
      investigations about SME control of elements in the aspect of material
      processing. In the present work, the ability to control the shape memory (SM) of
      bioresorbable and semicrystalline poly(L-lactide) (PLLA) is investigated. The
      studies are based on the unexpected effect of material orientation which was
      demonstrated even at low percentage deformation in crystallized mould injected
      material. The presented studies revealed that the different degrees of
      crystallinity obtained during processing might be a useful switch to create a
      tailored SME for a specific application. The prepared samples of variable
      morphology revealed a possibility to control the value of material stress during
      permanent shape recovery. The degree of shape recovery of the prepared samples
      was also controlable. The highest stress value observed during permanent shape
      recovery reached 10MPa for the sample annealed 60min at 115 degrees C even when
      the sample was only deformed in 8%. The other significant aspect of this work is
      to present the problem of slow crystallization of the material during and after
      processing (cooling rate) as well as the possibility of negative SME change
      during the shelf life of the fabric.

PMID- 27871053
TI  - Quality by Design in the development of hydrophilic interaction liquid
      chromatography method with gradient elution for the analysis of olanzapine.
AB  - This paper deals with the development of hydrophilic interaction liquid
      chromatography (HILIC) method with gradient elution, in accordance with
      Analytical Quality by Design (AQbD) methodology, for the first time. The method
      is developed for olanzapine and its seven related substances. Following step by
      step AQbD methodology, firstly as critical process parameters (CPPs) temperature,
      starting content of aqueous phase and duration of linear gradient are recognized,
      and as critical quality attributes (CQAs) separation criterion S of critical
      pairs of substances are investigated. Rechtschaffen design is used for the
      creation of models that describe the dependence between CPPs and CQAs. The design
      space that is obtained at the end is used for choosing the optimal conditions
      (set point). The method is fully validated at the end to verify the adequacy of
      the chosen optimal conditions and applied to real samples.

PMID- 27871051
TI  - Aging modifies the effect of GCH1 RS11158026 on DAT uptake and Parkinson's
      disease clinical severity.
AB  - Novel single nucleotide polymorphisms within Parkinson's disease (PD) can predict
      disease risk, but their influence on clinical, cognitive, and neurobiological
      indices remains unexplored. We investigated differences between functional
      polymorphisms at RS11158026 coding for guanosine triphosphate cyclohydrolase-1
      (GCH1), an essential enzyme for dopamine production in nigrostriatal cells. Among
      newly diagnosed, untreated PD subjects and age-matched controls from the
      Parkinson's Progression Markers Initiative, T allele carriers showed higher PD
      risk (odds ratio = 1.23, p = 0.048), earlier age of onset by 5 years (p = 0.003),
      and lower striatal dopamine reuptake transporter uptake (p = 0.003). Carriers
      also had increased cerebrospinal fluid alpha-synuclein (p = 0.016), worse motor
      function (p = 0.041), anxiety (p = 0.038), and executive function (p < 0.001).
      Strikingly, these effects were only in younger T carriers (<50 years), where
      aging quells the effects of these genetic factors. This suggests GCH1 variants
      affect early PD risk through altered dopamine uptake, and aging alters how
      genetic factors contribute to disease development. Future studies should
      investigate how aging modifies genotypes' contributions on PD risk and sequelae.

PMID- 27871054
TI  - Lipophilicity estimation and characterization of selected steroid derivatives of
      biomedical importance applying RP HPLC.
AB  - The present paper deals with chromatographic lipophilicity determination of
      twenty-nine selected steroid derivatives using reversed-phase high-performance
      liquid chromatography (RP HPLC) combined with two mobile phase, acetonitrile
      water and methanol-water. Chromatographic behavior of four groups (triazole and
      tetrazole, toluenesulfonylhydrazide, nitrile and dinitrile and dione) of selected
      steroid derivatives was studied. Investigated compounds were grouped using
      principal component analysis (PCA) according to their logk values for both mobile
      phases. Grouping was in the very good accordance with the polarity and
      lipophilicity of the investigated compounds. QSRR (quantitative structure
      retention relationship) approach was used to model chromatographic lipophilicity
      behavior using molecular descriptors. Modeling was performed using linear
      regression (LR) and multiple linear regression (MLR) methods. The most
      influential molecular descriptors were lipophilicity descriptors that are
      important for molecules ability to pass through biological membranes and
      geometrical descriptors. All established LR-QSRR and MLR-QSRR models were
      statistically validated by standards, cross- and external validation parameters
      as well as with two graphical methods. According to all these assessments, MLR
      models were better for chromatographic lipophilicity prediction. It was shown
      that chromatographic systems with methanol-water were better for modeling of logk
      than systems with acetonitrile-water, as well as the systems that contained lower
      volume fractions of organic component in mobile phase. Modeling was performed in
      order to obtain lipophilicity profiles of investigated compounds as future drug
      candidates of biomedical importance.

PMID- 27871055
TI  - Microfluidic device for label-free quantitation and distinction of bladder cancer
      cells from the blood cells using micro machined silicon based electrical
      approach; suitable in urinalysis assays.
AB  - This paper introduces an integrated microfluidic chip as a promising tool to
      measure the concentration of bladder cancer cells (BCC) in urine samples. Silicon
      microchannels were used as trapping gates for both floated BCC and leukocytes
      which are found in the urine of patients. By the assistance of the gold
      electrodes patterned at the bottom of the micro gates, the capacitance of
      captured cancerous and blood cells were measured. Different membrane capacitance
      between BCC and leukocyte was the indicative signal for diagnosing the nature of
      captured cells in a urine like solution. The concentration range of the target
      that could be detected was about 10 BCCs per one chip. Such response has been
      achieved without applying any biochemical or florescent markers. Thus, it could
      be a simple and cheap approach to support cytological and immune-fluorescent
      assays. The limit of detection was approximately 1 cancerous cell/11 leukocytes
      in 1ml of the urine like solution. The entire measurement time was less than an
      hour. Consequently, this electrical microfluidic device promises significant
      potential in urinalysis.

PMID- 27871056
TI  - Fampridine treatment and walking distance in multiple sclerosis: A randomised
      controlled trial.
AB  - OBJECTIVE: To explore the benefits of modified-release fampridine on walking
      distance in MS. METHODS: This was a randomised double-blind, placebo-controlled
      crossover trial of fampridine in 25 MS patients. The primary outcome measure was
      the six minute walk test (6MWT). A p-value<10% led to rejection of the null
      hypothesis. RESULTS: The pre-specified criterion for statistical significance was
      met, with a 17m improvement in 6MWT in the treatment arm. In addition, baseline
      S2 accommodation, a nerve excitability parameter that reflects slow K+ channel
      activity, modified the effect of fampridine. For patients who had abnormally high
      S2 accommodation values, there was a 28m improvement in the 6MWT (p=0.04). In
      contrast, for patients with low S2 values, a 0m improvement was noted (p=1.0).
      CONCLUSION: The study provides evidence that fampridine may improve walking
      distance. Nerve excitability assessment may be useful in selecting those patients
      who are most likely to gain benefit from fampridine. SIGNIFICANCE: Fampridine may
      improve walking distance in MS. Nerve excitability assessment may assist in
      identifying those patients most likely to respond to fampridine.

PMID- 27871058
TI  - Short synthesis of phenylpropanoid glycoside grayanoside-A and analogues.
AB  - A short synthesis of phenylethyl glycosides grayanoside-A 1, 2 and analogues 3-4
      in high 43-65% overall yields is described. The main synthetic step involved
      regioselective O-6 acylation of unprotected 2-phenylethyl-beta-D-glucoside 7 with
      cinnamoyl chlorides 8a-d using Me2SnCl2 as catalyst. The acylation at O-6 is
      regioselective regardless of the type of cinnamoyl chloride used.
      Protection/deprotection steps of the glucoside core were not necessary. The
      synthetic route is generally applicable for the synthesis of phenylpropanoid
      glycoside class of compounds acylated at O-6.

PMID- 27871057
TI  - Mechanistic insights into GPCR-G protein interactions.
AB  - G protein-coupled receptors (GPCRs) respond to extracellular stimuli and interact
      with several intracellular binding partners to elicit cellular responses,
      including heterotrimeric G proteins. Recent structural and biophysical studies
      have highlighted the dynamic nature of GPCRs and G proteins and have identified
      specific conformational changes important for receptor-mediated nucleotide
      exchange on Galpha. While domain separation within Galpha is necessary for GDP
      release, opening the inter-domain interface is insufficient to stimulate
      nucleotide exchange. Rather, an activated receptor promotes GDP release by
      allosterically disrupting the nucleotide-binding site via interactions with the
      Galpha N-termini and C-termini. Highlighting the allosteric nature of GPCRs,
      recent studies suggest that agonist binding alone poorly stabilizes an active
      conformation of several receptors. Rather, full stabilization of the receptor in
      an active state requires formation of the agonist-receptor-G protein ternary
      complex. In turn, nucleotide-free Galpha is able to stabilize conformational
      changes around the receptor's agonist-binding site to enhance agonist affinity.

PMID- 27871060
TI  - Involvement of serum glucocorticoid-regulated kinase 1 in reproductive success.
AB  - Reproductive processes, in particular events that concern pregnancy, are fine
      tuned to produce offspring. Reproductive success is of prime importance for the
      survival of every species. The highly conserved and ubiquitously expressed serum
      glucocorticoid-regulated kinase 1 (SGK1) was first implicated in infertility as a
      regulator of a Na+ channel. In this review, we emphasize the prominent role of
      SGK1 during early pregnancy: 1) balancing uterine luminal fluid secretion and
      reabsorption to aid blastocyst adhesion and to import nutrients and energy; 2)
      transducing signals from the blastocyst to the receptive endometrium; 3) inducing
      multiple genes that are involved in uterine receptivity and trophoblast invasion;
      4) regulating cell differentiation and antioxidant defenses at the fetomaternal
      interface; and 5) contributing to the proliferation and survival of decidual
      stromal cells. Accordingly, SGK1 coordinates many cellular processes that are
      crucial to reproductive activities. Aberrant expression or function of SGK1
      results in implantation failure and early pregnancy loss. Further investigation
      of the molecular mechanisms of the function of SGK1 might provide novel
      diagnostic tools and interventions for reproductive complications.-Lou, Y., Hu,
      M., Mao, L., Zheng, Y., Jin, F. Involvement of serum glucocorticoid-regulated
      kinase 1 in reproductive success.

PMID- 27871059
TI  - Selective p38alpha MAP kinase/MAPK14 inhibition in enzymatically modified LDL
      stimulated human monocytes: implications for atherosclerosis.
AB  - The first ATP-competitive p38alpha MAPK/MAPK14 inhibitor with excellent in vivo
      efficacy and selectivity, skepinone-L, is now available. We investigated the
      impact of selective p38alpha MAPK/MAPK14 inhibition on enzymatically modified LDL
      (eLDL) stimulated human monocytes with its implications for atherosclerosis.
      Among the different p38 MAPK isoforms, p38alpha/MAPK14 was the predominantly
      expressed and activated isoform in isolated human peripheral blood monocytes.
      Moreover, eLDL colocalized with macrophages positive for p38alpha MAPK/MAPK14 in
      human carotid endarterectomy specimens. Using the human leukemia cell line THP-1
      and/or primary monocyte-derived macrophages, skepinone-L inhibited eLDL-induced
      activation of the p38 MAPK pathway, inhibited eLDL induced expression of both
      cluster of differentiation 36 (CD36) and ATP-binding cassette, subfamily A,
      member 1 (ABCA1), without a net effect on foam cell formation, had a cell- and
      time-dependent effect on eLDL-triggered apoptosis, and inhibited eLDL-stimulated
      secretion of IL-8 and MIP-1beta/CCL4 (macrophage inflammatory protein
      1beta/chemokine, CC motif, ligand 4). Inhibition of a key signaling molecule of
      the p38 MAPK pathway, p38alpha MAPK/MAPK14, by selective inhibitors like
      skepinone-L, conclusively facilitates elucidation of the impact of the complex
      network of p38 MAPK signaling on atherogenesis and might provide a promising
      therapeutic tool to prevent inflammatory cascades in atherosclerosis.-Cheng, F.,
      Twardowski, L., Fehr, S., Aner, C., Schaeffeler, E., Joos, T., Knorpp, T.,
      Dorweiler, B., Laufer, S., Schwab, M., Torzewski, M. Selective p38alpha MAP
      kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human
      monocytes: implications for atherosclerosis.

PMID- 27871061
TI  - A small-molecule inhibitor of NF-kappaB-inducing kinase (NIK) protects liver from
      toxin-induced inflammation, oxidative stress, and injury.
AB  - Potent and selective chemical probes are valuable tools for discovery of novel
      treatments for human diseases. NF-kappaB-inducing kinase (NIK) is a key trigger
      in the development of liver injury and fibrosis. Whether inhibition of NIK
      activity by chemical probes ameliorates liver inflammation and injury is largely
      unknown. In this study, a small-molecule inhibitor of NIK, B022, was found to be
      a potent and selective chemical probe for liver inflammation and injury. B022
      inhibited the NIK signaling pathway, including NIK-induced p100-to-p52 processing
      and inflammatory gene expression, both in vitro and in vivo Furthermore, in vivo
      administration of B022 protected against not only NIK but also CCl4-induced liver
      inflammation and injury. Our data suggest that inhibition of NIK is a novel
      strategy for treatment of liver inflammation, oxidative stress, and injury.-Ren,
      X., Li, X., Jia, L., Chen, D., Hou, H., Rui, L., Zhao, Y., Chen, Z. A small
      molecule inhibitor of NF-kappaB-inducing kinase (NIK) protects liver from toxin
      induced inflammation, oxidative stress, and injury.

PMID- 27871062
TI  - Unmasking ultradian rhythms in gene expression.
AB  - Biological oscillations with an ultradian time scale of 1 to several hours
      include cycles in behavioral arousal, episodic glucocorticoid release, and gene
      expression. Ultradian rhythms are thought to have an extrinsic origin because of
      a perceived absence of ultradian rhythmicity in vitro and a lack of known
      molecular ultradian oscillators. We designed a novel, non-spectral-analysis
      method of separating ultradian from circadian components and applied it to a
      published gene expression dataset with an ultradian sampling resolution.
      Ultradian rhythms in mouse hepatocytes in vivo have been published, and we
      validated our approach using this control by confirming 175 of 323 ultradian
      genes identified in a prior study and found 862 additional ultradian genes. For
      the first time, we now report ultradian expression of >900 genes in vitro Sixty
      genes exhibited ultradian transcriptional rhythmicity, both in vivo and in vitro,
      including 5 genes involved in the cell cycle. Within these 60 genes, we
      identified significant enrichment of specific DNA motifs in the 1000 bp proximal
      promotor, some of which associate with known transcriptional factors. These
      findings are in strong support of instrinsically driven ultradian rhythms and
      expose potential molecular mechanisms and functions underlying ultradian rhythms
      that remain unknown.-Van der Veen, D. R., Gerkema, M. P. Unmasking ultradian
      rhythms in gene expression.

PMID- 27871063
TI  - Dioscorea esculenta-induced increase in muscle sex steroid hormones is associated
      with enhanced insulin sensitivity in a type 2 diabetes rat model.
AB  - The effects of chronic Dioscorea esculenta administration and exercise training
      on muscle sex steroid hormone levels and insulin resistance in type 2 diabetes
      rats was assessed. Twenty-week-old male Otsuka Long Evans Tokushima Fatty (OLETF)
      rats were assigned randomly to the control, D. esculenta treatment, D. esculenta
      with 5alpha-reductase inhibitor treatment, or the exercise training groups
      (running at 25 m/min for 1 h, 5 d/wk; n = 10 each group). Eight weeks of D.
      esculenta treatment or exercise training significantly attenuated the increase in
      plasma insulin and fasting glucose levels. Plasma and muscle concentrations of
      dehydroepiandrosterone and 5alpha-dihydrotestosterone (DHT) and the expression of
      5alpha-reductase increased significantly in the D. esculenta-treated and exercise
      training groups, and both treatments led to the upregulation of glucose
      transporter-4 translocation with concomitant increases in PKB and PKC-zeta/lambda
      phosphorylation. Furthermore, the glucose metabolic clearance rate, which
      represents insulin sensitivity, increased significantly in both the D. esculenta
      treated and exercise training groups. These effects were suppressed by
      administration of the DHT synthetic inhibitor. Together, these findings suggest
      that the D. esculenta-induced increase in muscle sex steroid hormone levels helps
      decrease insulin resistance in type 2 diabetes.-Sato, K., Fujita, S., Iemitsu, M.
      Dioscorea esculenta-induced increase in muscle sex steroid hormones is associated
      with enhanced insulin sensitivity in a type 2 diabetes rat model.

PMID- 27871065
TI  - Mechanical remodeling of normally sized mammalian cells under a gravity vector.
AB  - Translocation of the dense nucleus along a gravity vector initiates mechanical
      remodeling of a cell, but the underlying mechanisms of cytoskeletal network and
      focal adhesion complex (FAC) reorganization in a mammalian cell remain unclear.
      We quantified the remodeling of an MC3T3-E1 cell placed in upward-, downward-, or
      edge-on-orientated substrate. Nucleus longitudinal translocation presents a high
      value in downward orientation at 24 h or in edge-on orientation at 72 h, which is
      consistent with orientation-dependent distribution of perinuclear actin stress
      fibers and vimentin cords. Redistribution of total FAC area and fractionized
      super mature adhesion number coordinates this dependence at short duration. This
      orientation-dependent remodeling is associated with nucleus flattering and lamin
      A/C phosphorylation. Actin depolymerization or Rho-associated protein kinase
      signaling inhibition abolishes the orientation dependence of nucleus
      translocation, whereas tubulin polymerization inhibition or vimentin disruption
      reserves the dependence. A biomechanical model is therefore proposed for
      integrating the mechanosensing of nucleus translocation with cytoskeletal
      remodeling and FAC reorganization induced by a gravity vector.-Zhang, C., Zhou,
      L., Zhang, F., Lu, D., Li, N., Zheng, L., Xu, Y., Li, Z., Sun, S., Long, M.
      Mechanical remodeling of normally sized mammalian cells under a gravity vector.

PMID- 27871064
TI  - Benzopyrimido-pyrrolo-oxazine-dione CFTR inhibitor (R)-BPO-27 for antisecretory
      therapy of diarrheas caused by bacterial enterotoxins.
AB  - Secretory diarrheas caused by bacterial enterotoxins, including cholera and
      traveler's diarrhea, remain a major global health problem. Inappropriate
      activation of the cystic fibrosis transmembrane conductance regulator (CFTR)
      chloride channel occurs in these diarrheas. We previously reported that the
      benzopyrimido-pyrrolo-oxazinedione (R)-BPO-27 inhibits CFTR chloride conductance
      with low-nanomolar potency. Here, we demonstrate using experimental mouse models
      and human enterocyte cultures the potential utility of (R)-BPO-27 for treatment
      of secretory diarrheas caused by cholera and Escherichia coli enterotoxins. (R)
      BPO-27 fully blocked CFTR chloride conductance in epithelial cell cultures and
      intestine after cAMP agonists, cholera toxin, or heat-stable enterotoxin of E.
      coli (STa toxin), with IC50 down to ~5 nM. (R)-BPO-27 prevented cholera toxin and
      STa toxin-induced fluid accumulation in small intestinal loops, with IC50 down to
      0.1 mg/kg. (R)-BPO-27 did not impair intestinal fluid absorption or inhibit other
      major intestinal transporters. Pharmacokinetics in mice showed >90% oral
      bioavailability with sustained therapeutic serum levels for >4 h without the
      significant toxicity seen with 7-d administration at 5 mg/kg/d. As evidence to
      support efficacy in human diarrheas, (R)-BPO-27 blocked fluid secretion in
      primary cultures of enteroids from human small intestine and anion current in
      enteroid monolayers. These studies support the potential utility of (R)-BPO-27
      for therapy of CFTR-mediated secretory diarrheas.-Cil, O., Phuan, P.-W.,
      Gillespie, A. M., Lee, S., Tradtrantip, L., Yin, J., Tse, M., Zachos, N. C., Lin,
      R., Donowitz, M., Verkman, A. S. Benzopyrimido-pyrrolo-oxazine-dione CFTR
      inhibitor (R)-BPO-27 for antisecretory therapy of diarrheas caused by bacterial
      enterotoxins.

PMID- 27871067
TI  - The lncRNA SNHG5/miR-32 axis regulates gastric cancer cell proliferation and
      migration by targeting KLF4.
AB  - Long noncoding RNAs (lncRNAs) are emerging as important regulators in cellular
      processes, including the development, proliferation, and migration of cancer
      cells. We have demonstrated in a prior study that small nucleolar RNA host gene 5
      (SNHG5) is dysregulated in gastric cancer (GC). To further explore the underlying
      mechanisms of SNGH5 function in the development of GC, in this study, we screened
      the microRNAs interacting with SNHG5 and elucidated their roles in GC. We showed
      that SNHG5 contains a putative miR-32-binding site and that deletion of this site
      abolishes the responsiveness to miR-32. Suppression of SNHG5 expression by miR-32
      was found to be Argonaute (Ago)2-dependent. Immunoprecipitation showed that SNHG5
      could be pulled down from the Ago-2 complex with miR-32. Furthermore, it was
      reported that Kruppel-like factor 4 (KLF4) is a target gene of miR-32. In
      agreement with SNHG5 being a decoy for miR-32, we showed that KLF4 suppression by
      miR-32 could be partially rescued by SNHG5 overexpression, whereas miR-32 mimic
      rescued SNHG5 overexpression-mediated suppression of GC cell migration. In
      addition, we identified a negative correlation between the expression of SNHG5
      and miR-32 in GC tissues. Furthermore, KLF4 expression was significantly
      downregulated in GC specimens, and a negative correlation between miR-32 and KLF4
      expression and a positive correlation between KLF4 and SNHG5 expression levels
      were detected. Overall, this study demonstrated, for the first time, that the
      SNHG5/miR-32/KLF4 axis functions as an important player in GC cell migration and
      potentially contributes to the improvement of GC diagnosis and therapy.-Zhao, L.,
      Han, T., Li, Y., Sun, J., Zhang, S., Liu, Y., Shan, B., Zheng D., Shi, J. The
      lncRNA SNHG5/miR-32 axis regulates gastric cancer cell proliferation and
      migration by targeting KLF4.

PMID- 27871066
TI  - A novel amino acid and metabolomics signature in mice overexpressing muscle
      uncoupling protein 3.
AB  - Uncoupling protein 3 (UCP3) is highly selectively expressed in skeletal muscle
      and is known to lower mitochondrial reactive oxygen species and promote fatty
      acid oxidation; however, the global impact of UCP3 activity on skeletal muscle
      and whole-body metabolism have not been extensively studied. We utilized
      untargeted metabolomics to identify novel metabolites that distinguish mice
      overexpressing UCP3 in muscle, both at rest and after exercise regimens that
      challenged muscle metabolism, to potentially unmask subtle phenotypes. Male wild
      type (WT) and muscle-specific UCP3-overexpressing transgenic (UCP3 Tg) C57BL/6J
      mice were compared with or without a 5 wk endurance training protocol at rest or
      after an acute exercise bout (EB). Skeletal muscle, liver, and plasma samples
      were analyzed by gas chromatography time-of-flight mass spectrometry.
      Discriminant metabolites were considered if within the top 99th percentile of
      variable importance measurements obtained from partial least-squares discriminant
      analysis models. A total of 80 metabolites accurately discriminated UCP3 Tg mice
      from WT when modeled within a specific exercise condition (i.e.,
      untrained/rested, endurance trained/rested, untrained/EB, and endurance
      trained/EB). Results revealed that several amino acids and amino acid derivatives
      in skeletal muscle and plasma of UCP3 Tg mice (e.g., Asp, Glu, Lys, Tyr, Ser,
      Met) were significantly reduced after an EB; that metabolites associated with
      skeletal muscle glutathione/Met/Cys metabolism (2-hydroxybutanoic acid,
      oxoproline, Gly, and Glu) were altered in UCP3 Tg mice across all training and
      exercise conditions; and that muscle metabolite indices of dehydrogenase activity
      were increased in UCP3 Tg mice, suggestive of a shift in tissue NADH/NAD+ ratio.
      The results indicate that mitochondrial UCP3 activity affects metabolism well
      beyond fatty acid oxidation, regulating biochemical pathways associated with
      amino acid metabolism and redox status. That select metabolites were altered in
      liver of UCP3 Tg mice highlights that changes in muscle UCP3 activity can also
      affect other organ systems, presumably through changes in systemic metabolite
      trafficking.-Aguer, C., Piccolo, B. D., Fiehn, O., Adams, S. H., Harper, M.-E. A
      novel amino acid and metabolomics signature in mice overexpressing muscle
      uncoupling protein 3.

PMID- 27871068
TI  - Autoinflammatory Skin Disease: A Review of Concepts and Applications to General
      Dermatology.
AB  - We provide an up-to-date summary of important concepts of autoinflammation as
      well as describe important but rare monogenic autoinflammatory disorders that may
      present with cutaneous findings. Finally, of particular interest to a practicing
      general dermatology audience, we review concepts of autoinflammation as they
      apply to understanding the disease pathogenesis of common skin disorders.

PMID- 27871069
TI  - Rate and Predictors of Interval Esophageal and Gastric Cancers after
      Esophagogastroduodenoscopy in the United States.
AB  - BACKGROUND AND AIMS: In the United States, little is known about the rates of
      interval upper gastrointestinal (GI) cancer (possibly missed out) after an
      esophagogastroduodenoscopy (EGD) is performed. Data from non-US studies reported
      interval cancer rates of 7-26%. We aimed to study the rate and predictors of
      interval upper GI cancers in the United States. METHODS: Using the random 5%
      sample of Medicare beneficiaries in the Surveillance, Epidemiology, and End
      Results-Medicare linked database, we identified patients diagnosed with
      esophageal or gastric cancer during 2000-2007. EGD performed within 36 months
      prior to cancer diagnosis was identified using CPT codes. Cancers diagnosed 6-36
      months after EGD were defined as interval (vs. detected) cancers. The chi-square
      test and the multivariate logistic model were used in statistical analysis.
      RESULTS: Of 751 patients diagnosed with upper GI cancer, 52 patients (6.9%) were
      diagnosed with interval cancers 6-36 months after EGD. The rate of interval
      cancers was 5.5% (31/568) for gastroenterologists and 11.5% (21/183) for non
      gastroenterologists (p < 0.01). In multivariate logistic regression, EGDs
      performed by gastroenterologists (vs. non-gastroenterologists: OR 0.46, 95% CI
      0.25-0.83) and those in inpatient setting (vs. outpatient: OR 0.53, 95% CI 0.28
      0.997) were associated with a lower likelihood of interval cancers. Sensitivity
      analyses limited to outpatient EGDs or interval cancers 6-30 months after EGDs
      led to similar results. CONCLUSIONS: The rate of interval cancers after EGD is
      the same as the rate of colonoscopy among Medicare patients in the United States.
      EGDs performed by gastroenterologists and in in-patient settings were associated
      with a lesser likelihood of interval cancers.

PMID- 27871070
TI  - Khat (Catha edulis) and Obesity: A Scoping Review of Animal and Human Studies.
AB  - BACKGROUND: Khat (Catha edulis) is a plant that is deeply rooted in the cultural
      life of East African and Southwestern Arabian populations. Prevalent traditional
      beliefs about khat are that the plant has an effect on appetite and body weight.
      SUMMARY: This review assesses the accumulated evidences on the mutual influence
      of monoamines, hormones and neuropeptides that are linked to obesity. A few anti
      obesity drugs that exert their mechanisms of action through monoamines are
      briefly discussed to support the notion of monoamines being a critical target of
      drug discovery for new anti-obesity drugs. Subsequently, the review provides a
      comprehensive overview of central dopamine and serotonin changes that are
      associated with the use of khat or its alkaloids. Then, all the studies on khat
      that describe physical, biochemical and hormonal changes are summarised and
      discussed in depth. CONCLUSION: The reviewed studies provide relatively
      acceptable evidence that different khat extracts or cathinone produces changes in
      terms of weight, fat mass, appetite, lipid biochemistry and hormonal levels.
      These changes are more pronounced at higher doses and long durations of
      intervention. The most suggested mechanism of these changes is the central action
      that produces changes in the physiology of dopamine and serotonin. Nonetheless,
      there are a number of variations in the study design, including species, doses
      and durations of intervention, which makes it difficult to arrive at a final
      conclusion about khat regarding obesity, and further studies are necessary in the
      future to overcome these limitations.

PMID- 27871071
TI  - WT1 Expression in Patients with Myelodysplastic Syndromes: A Variety of
      Possibilities in Future Clinical Practice.

PMID- 27871073
TI  - Expression of Kisspeptin in Gonadotrope Precursors in the Mouse Pituitary during
      Embryonic and Postnatal Development and in Adulthood.
AB  - BACKGROUND: Kisspeptins are important regulators of the development and function
      of the hypothalamic-pituitary-gonadal axis. However, the importance of kisspeptin
      at the pituitary level is unclear. METHODS: We examined the expression profile of
      kisspeptin in the mouse pituitary during development and in adulthood using RT
      PCR, quantitative PCR and immunohistochemistry. RESULTS: Kiss1 mRNA was detected
      in both embryonic and postnatal pituitaries. Kisspeptin-immunoreactive (+) cells
      were detected from embryonic day (E) 13.5 throughout adulthood, being localized
      to the rostroventral portion in the anterior pituitary (AP) in embryos, and also
      to the dorsocaudal AP postnatally. A large proportion of kisspeptin+ cells were
      double-labeled with gonadotrope markers including Foxl2, SF-1, and LHbeta, and
      the percentage of LHbeta+ cells in kisspeptin+ cells increased during
      development. No kisspeptin+ cells were positive for the proliferating cell marker
      MCM7 (minichromosome maintenance protein 7), but a few kisspeptin+ cells co
      expressed the stem/progenitor cell marker Sox2. Kisspeptin expression was similar
      between sexes and between agonadal SF-1 knockout embryos and wild-type
      littermates. Kiss1 mRNA levels were not significantly different between sexes or
      during early postnatal development, but levels in females increased when puberty
      began and were significantly higher than in males at postpubertal ages.
      CONCLUSIONS: These results suggest that kisspeptin is expressed in gonadotrope
      precursors during gonadotrope differentiation, and that kisspeptin expression
      begins soon after the initiation of alphaGSU production and is extinguished soon
      after the initiation of LH production. Furthermore, pituitary kisspeptin
      expression may be regulated in a gonad-independent manner during development, but
      may be associated with gonadotrope function in adulthood.

PMID- 27871074
TI  - Comparison of the HiFocus Mid-Scala and HiFocus 1J Electrode Array: Angular
      Insertion Depths and Speech Perception Outcomes.
AB  - The HiFocus Mid-Scala (MS) electrode array has recently been introduced onto the
      market. This precurved design with a targeted mid-scalar intracochlear position
      pursues an atraumatic insertion and optimal distance for neural stimulation. In
      this study we prospectively examined the angular insertion depth achieved and
      speech perception outcomes resulting from the HiFocus MS electrode array for 6
      months after implantation, and retrospectively compared these with the HiFocus 1J
      lateral wall electrode array. The mean angular insertion depth within the MS
      population (n = 96) was found at 470 degrees . This was 50 degrees  shallower but
      more consistent than the 1J electrode array (n = 110). Audiological evaluation
      within a subgroup, including only postlingual, unilaterally implanted, adult
      cochlear implant recipients who were matched on preoperative speech perception
      scores and the duration of deafness (MS = 32, 1J = 32), showed no difference in
      speech perception outcomes between the MS and 1J groups. Furthermore, speech
      perception outcome was not affected by the angular insertion depth or frequency
      mismatch.

PMID- 27871072
TI  - Testosterone Rapidly Augments Retrograde Endocannabinoid Signaling in
      Proopiomelanocortin Neurons to Suppress Glutamatergic Input from Steroidogenic
      Factor 1 Neurons via Upregulation of Diacylglycerol Lipase-alpha.
AB  - Testosterone exerts profound effects on reproduction and energy homeostasis. Like
      other orexigenic hormones, it increases endocannabinoid tone within the
      hypothalamic feeding circuitry. Therefore, we tested the hypothesis that
      testosterone upregulates the expression of diacylglycerol lipase (DAGL)alpha in
      the hypothalamic arcuate nucleus (ARC) to increase energy intake via enhanced
      endocannabinoid-mediated retrograde inhibition of anorexigenic
      proopiomelanocortin (POMC) neurons. Energy intake, meal patterns, and energy
      expenditure were evaluated in orchidectomized, male guinea pigs treated
      subcutaneously with testosterone propionate (TP; 400 MUg) or its sesame oil
      vehicle (0.1 mL). TP rapidly increased energy intake, meal size, O2 consumption,
      CO2 production, and metabolic heat production, all of which were antagonized by
      prior administration of the DAGL inhibitor orlistat (3 MUg) into the third
      ventricle. These orlistat-sensitive, TP-induced increases in energy intake and
      expenditure were temporally associated with a significant elevation in ARC
      DAGLalpha expression. Electrophysiological recordings in hypothalamic slices
      revealed that TP potentiated depolarization-induced suppression of excitatory
      glutamatergic input onto identified ARC POMC neurons, which was also abolished by
      orlistat (3 MUM), the CB1 receptor antagonist AM251 (1 MUM), and the AMP
      activated protein kinase inhibitor compound C (30 MUM) and simulated by transient
      bath application of the dihydrotestosterone mimetic Cl-4AS-1 (100 nM) and
      testosterone-conjugated bovine serum albumin (100 nM). Thus, testosterone boosts
      DAGLalpha expression to augment retrograde, presynaptic inhibition of glutamate
      release onto ARC POMC neurons that, in turn, increases energy intake and
      expenditure. These studies advance our understanding of how androgens work within
      the hypothalamic feeding circuitry to affect changes in energy balance.

PMID- 27871075
TI  - Comparative Effectiveness of Renin-Angiotensin System Antagonists in Maintenance
      Dialysis Patients.
AB  - BACKGROUND/AIMS: Whether angiotensin converting enzyme inhibitors (ACE) and
      angiotensin receptor blockers (ARB) are differentially associated with reductions
      in cardiovascular events and mortality in patients receiving maintenance dialysis
      is uncertain. We compared outcomes between ACE and ARB users among hypertensive,
      maintenance dialysis patients. METHODS: National retrospective cohort study of
      hypertensive, Medicare-Medicaid eligible patients initiating chronic dialysis
      between 1/1/2000 to 12/31/2005. The exposure of interest was new use of either an
      ACEI or ARB. Outcomes were all-cause mortality (ACM) and combined cardiovascular
      hospitalization or death (CV-endpoint). Cox proportion hazards models were used
      to compare the effect of ACEI vs ARB use on ACM and, separately, CV-endpoint.
      RESULTS: ACM models were based on 3,555 ACEI and 1,442 ARB new users, while CV
      endpoint models included 3,289 ACEI and 1,346 ARB new users. After statistical
      adjustments, ACEI users had higher hazard ratios for ACM (AHR = 1.22, 99% CI 1.05
      1.42) and CV-endpoint (AHR = 1.12, 99% CI 0.99-1.27). CONCLUSIONS: Patients
      initiating maintenance dialysis who received an ACEI faced an increased risk for
      mortality and a trend towards an increased risk for CV-endpoints when compared to
      patients who received an ARB. Validation of these results in a rigorous clinical
      trial is warranted.

PMID- 27871076
TI  - Semi-Rigid Ureteroscopy for Proximal Ureteral Stones: Does Adjunctive Tamsulosin
      Therapy Increase the Chance of Success?
AB  - OBJECTIVES: To assess the efficacy of adjunctive tamsulosin therapy in improving
      the success rate of laser-assisted semi-rigid ureteroscopy (URS) for removing
      proximal ureteral stones. PATIENTS AND METHODS: This prospective study included
      165 patients with proximal ureteral stones >=10 mm. The patients were randomly
      assigned to a tamsulosin group (Group I, n = 81) receiving tamsulosin 0.4 mg
      daily for 1 week pre-URS and a control group (Group II, n = 84) without
      tamsulosin therapy. Treatment consisted of URS using a semi-rigid ureteroscope
      (7.5 Fr), followed by intracorporeal holmium: YAG laser lithotripsy. The patients
      were followed up regularly for 8 weeks after URS. RESULTS: The operative time was
      43.4 and 49.6 min in Groups I and II, respectively (p < 0.001). Scope to stone
      access rate was 93.8 and 82.1% in patients of Groups I and II, respectively (p =
      0.022). The stone-free rate was significantly higher in Group I compared to Group
      II (74/81; 91.4% vs. 67/84; 79.8%; p = 0.035). The complication rate was
      significantly lower in Group I compared to Group II (17.3 vs. 38.1%, p = 0.003).
      Only minor complications were encountered and were managed conservatively.
      CONCLUSIONS: Tamsulosin therapy prior to semi-rigid URS improved ureteroscopic
      access to proximal ureteral stones, thus leading to an increased success rate and
      low morbidity.

PMID- 27871077
TI  - Impact of Annexin A 7 Deficiency on FGF23 Plasma Concentrations.
AB  - BACKGROUND/AIMS: The release of fibroblast growth factor FGF23, a powerful
      regulator of 1,25(OH)2D3 formation and mineral metabolism, is stimulated by store
      operated Ca2+ entry (SOCE), which is accomplished by the pore forming Ca2+
      release activated channel protein Orai1. Regulators of Orai1 and thus FGF23
      release include serum & glucocorticoid inducible kinase SGK1, a kinase up
      regulated by glucocorticosteroids. Some effects of glucocorticoids require the
      presence of annexin A7, such as suppression of prostaglandin E2 in gastric
      glands. The present study thus explored whether annexin A7 impacts on FGF23
      plasma levels. METHODS: Comparisons were made between gene targeted mice lacking
      functional annexin A7 (Anx7-/-) and their wild type littermates (Anx7+/+). Serum
      C-terminal-FGF23, intact FGF23, 1,25(OH)2D3 and PTH concentrations were measured
      by ELISA or EIA. The serum and urinary phosphate concentrations were measured by
      colorimetry, the serum Ca2+ concentration and the urinary Ca2+ concentration by
      flame photometry. RESULTS: Serum C-terminal FGF23 levels and corticosterone
      levels were significantly higher and serum 1,25(OH)2 D3 and PTH levels were
      significantly lower in Anx7-/- than in Anx7+/+ mice. Water intake was slightly
      but significantly higher in Anx7-/- mice than in Anx7+/+ mice. No significant
      difference was observed between Anx7-/- and Anx7+/+ mice in urinary fluid
      excretion, plasma Ca2+ concentration, plasma phosphate concentration and urinary
      Ca2+ output. The urinary phosphate output was significantly lower in Anx7-/- mice
      than in Anx7+/+ mice. CONCLUSION: Annexin A7 deficiency upregulates FGF23 plasma
      levels, an effect paralleled by increased corticosterone plasma levels, as well
      as decreased 1,25(OH)2 D3 and PTH plasma levels.

PMID- 27871078
TI  - Cerebral Microhemorrhages and Meningeal Siderosis in Infective Endocarditis.
AB  - OBJECTIVE: Patients with infective endocarditis (IE) frequently experience
      cerebral insults, and neurological involvement in IE has been reported to herald
      a worse prognosis. In this manuscript, we describe a distinctive pattern of
      findings on susceptibility-weighted imaging (SWI) sequences in subjects with IE.
      METHODS: Patients with IE who underwent SWI MRI at an academic hospital from 2009
      to 2014 were retrospectively analyzed. The pattern of findings was compared to
      SWI findings in groups of subjects with cerebral amyloid angiopathy (CAA) or
      severe hypertension. RESULTS: Sixty-six subjects with IE were included; 64 (94%)
      had microhemorrhages and the average number per patient was 21.5. In 11 (17%)
      patients, microhemorrhages were the only neuroimaging abnormality. The majority
      of microhemorrhages were between 1 and 3 mm. In a direct comparison of gradient
      echo T2* (GRE-T2*) and SWI, many microhemorrhages in this size range were not
      detected by GRE-T2*. Microhemorrhages in IE involved every part of the brain with
      a significant predilection for the cerebellum. This pattern was distinct from
      that seen in hypertension or CAA. Small subarachnoid hemorrhage or meningeal
      siderosis were also frequently detected in IE, but were not associated with
      mycotic aneurysms. INTERPRETATION: SWI is a sensitive diagnostic technique for
      detecting infectious cerebral angiopathy in subjects with IE, producing a pattern
      of microhemorrhages that were distinct from other common microangiopathies.

PMID- 27871079
TI  - Triptolide Attenuates Inflammatory Response in Membranous Glomerulo-Nephritis Rat
      via Downregulation of NF-kappaB Signaling Pathway.
AB  - BACKGROUND/AIMS: Triptolide (TPL), a main active ingredient of Tripterygium
      wilfordii has been shown to exert anti-inflammatory effect. The role of TPL on
      glomerular diseases remains unclear. METHODS: This study aims to investigate the
      potential anti-inflammatory effect of TPL in rats with membranous
      glomerulonephritis (MGN). RESULTS: Our data showed that the pathological kidney
      damage was significantly alleviated by TPL treatment in MGN rats. We also found
      that MGN rats exhibited significantly higher (p < 0.01) level of inflammatory
      cytokines (TNF-alpha, IL-1beta and MCP-1) than those in normal group, while these
      inflammatory cytokines levels were significantly reduced in TPL treatment group
      compared with model group. Additionally, we found that TPL treatment could
      significantly decrease the malondialdehyde (MDA) level while enhanced superoxide
      dismutase (SOD) activity. Meanwhile, we also found that IkappaB kinase inhibitor
      (IMD-0354) could significantly reduce the accumulation of inflammation damage and
      oxidative lesions. Furthermore, we observed that both TPL and IMD-0354 treatment
      could block IkappaBalpha degradation and suppress mRNA and protein level of
      nuclear factor (NF) -kappaB p65. CONCLUSION: Together, all above results suggest
      that inflammatory response could be attenuated by TPL and this is partly due to
      the inhibition of NF- kappaB signaling pathway.

PMID- 27871080
TI  - The Association between Premature Adrenarche and Cardiovascular Risk May Be
      Greater than Expected.
AB  - AIM: The aim of this study was to investigate the cardiovascular risk of children
      with premature adrenarche (PA). METHODS: A total of 75 children (44 with PA and
      31 control subjects) aged 6-10 years were included in the study. Their metabolic,
      anthropometric, and echocardiographic parameters were recorded and compared.
      RESULTS: Triglyceride, DHEA-SO4, and 17-hydroxyprogesterone levels were
      significantly higher in the PA group (p = 0.04, p = 0.002, and p = 0.01,
      respectively). The echocardiographic assessments revealed that the left
      ventricular end-diastolic diameter (LVEDD) (p < 0.001), left ventricle (LV) and
      right ventricle (RV) ejection times (p = 0.031 and p = 0.035, respectively), and
      LV and RV Tei index measurements (p = 0.033 and p = 0.006, respectively) were
      significantly higher in the PA group than in the control group, whereas the E/e'
      ratio of the mitral lateral annulus was significantly lower in the PA group (p =
      0.006). Additionally, carotid intima-media thickness and epicardial adipose
      tissue measurements were significantly increased in the PA group compared to the
      control group (p < 0.001). CONCLUSION: Early atherosclerotic changes and
      subclinical impairment of cardiac function were observed in children with PA. It
      is possible that these children are on a course for early cardiovascular disease.

PMID- 27871081
TI  - Renal Complications in Patients with Renal Infarction: Prevalence and Risk
      Factors.
AB  - BACKGROUND/AIMS: This study aimed to investigate the incidence and risk factors
      for acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with
      renal infarction. METHODS: A single-center retrospective study was conducted from
      January 2005 to December 2013. Baseline and clinical characteristics of the
      enrolled patients with renal infarction were evaluated and analyzed according to
      the presence of AKI and CKD. In particular, predictors for AKI and CKD were
      determined using logistic regression analysis. RESULTS: Of the 105 patients
      included in present study, 41 (39.0%) patients had AKI. A total of 80 patients
      were followed up for 2 years after hospital discharge. Among these patients, 27
      (33.8%) patients had CKD. In the multivariate analysis, the predictors were mean
      blood pressure (odds ratio [OR] 1.062, 95% confidence interval [CI] 1.015-1.112,
      p = 0.009) and bilateral involvement (OR 4.396, 95% CI 1.096-17.632, p = 0.037)
      for AKI, and AKI (OR 14.799, 95% CI 4.173-52.490, p < 0.001) and old age (OR
      1.065, 95% CI 1.016-1.116, p = 0.009) for CKD. CONCLUSIONS: Physicians should pay
      attention to the development of AKI and CKD after renal infarction and follow
      patients over a long term.

PMID- 27871082
TI  - Self-Reported Physical Activity, Quality of Life, and Psychological Status in
      Relation to Plasma 25-Hydroxyvitamin D Concentration in Patients Treated with
      Hemodialysis.
AB  - BACKGROUND/AIMS: Vitamin D status is announced among factors that may influence
      physical performance and mental health. Our aim was to evaluate self-reported
      physical activity, quality of life, psychiatric functioning, and affects with
      respect to plasma 25-hydroxyvitamin D [25(OH)D] concentrations in HD patients.
      METHODS: The study was carried out in HD patients not receiving vitamin D
      supplements (n = 112). IPAQ-L, QLI-D, GHQ-28, and PANAS were used in
      psychological evaluations. Plasma 25(OH)D concentration was determined by a
      chemiluminescent microparticle immunoassay. RESULTS: Plasma 25(OH)D level was
      suboptimal in all patients (14.6 +/- 4.1 ng/ml). Adjusted correlates of 25(OH)D
      concentration included the GG genotype of GC rs7041 (beta+/-SE: 1.77+/- 0.70,
      P=0.014), female sex (beta+/-SE: -2.19+/-0.75, P=0.004), and treatment with high
      flux HD (beta+/-SE: 2.59+/-0.69, P=0.0003). In adjusted analyses, circulating
      25(OH)D showed the independent association with total activity related to
      domestic and gardening domain (beta+/-SE: 53.2+/-23.8, P=0.028), and with
      moderate-intensity activities (beta+/-SE: 54.9+/-27.4, P=0.048), but not with any
      of quality of life, psychiatric functioning, or affects measures. CONCLUSIONS:
      Vitamin D status is independently positively associated with physical activity in
      HD patients. Quality of life and mental health do not seem to be associated with
      circulating 25(OH)D under condition of its suboptimal levels.

PMID- 27871083
TI  - Work of Breathing in Fixed and Pressure Relief Continuous Positive Airway
      Pressure (C-FlexTM): A post hoc Analysis.
AB  - BACKGROUND: Expiratory pressure relief continuous positive airway pressure
      (pressure relief CPAP; C-FlexTM) causes increases in inspiratory duty cycle and
      shortening of expiratory time. It has been suggested that these changes are
      caused by an increase in work of breathing. OBJECTIVES: We studied the effects of
      C-Flex on work of breathing and intrinsic positive end-expiratory pressure as
      compared to fixed CPAP. METHODS: Work of breathing was analyzed in 24 patients
      with obstructive sleep apnea during treatment with fixed CPAP and C-Flex with 3
      different pressure relief settings in a randomized order during rapid-eye
      movement (REM) and non-REM sleep. Work of breathing was assessed on a breath-by
      breath basis using a piezoelectric esophageal pressure catheter and a
      pneumotachograph for measuring airflow. RESULTS: We found there was no increase
      in inspiratory work of breathing observed using C-Flex compared to fixed CPAP.
      Instead, we found a linear decrease in inspiratory work of breathing with
      increasing pressure relief, with a mean difference of 1.22 J/min between CPAP and
      maximum pressure release (C-Flex 3; 90% of the value with nasal CPAP); however,
      the decrease was not statistically significant. The decrease in inspiratory work
      of breathing associated with C-Flex has a significant inverse correlation with
      BMI. CONCLUSIONS: The C-Flex technology does not change work of breathing but
      shows a tendency towards a reduction of inspiratory work of breathing in patients
      with a lower BMI using higher C-Flex. The effect is probably caused by
      diminishing airway resistance generated by the positive end-expiratory pressure.
      Our findings may lead to additional fields of application of the C-Flex
      technology, such as chronic obstructive pulmonary disease or muscular dystrophy.

PMID- 27871084
TI  - Olmesartan Prevents Microalbuminuria in db/db Diabetic Mice Through Inhibition of
      Angiotensin II/p38/SIRT1-Induced Podocyte Apoptosis.
AB  - BACKGROUND/AIMS: Blockage of the renin-angiotensin II system (RAS) prevents or
      delays albuminuria in diabetic patients. The aim of this study was to investigate
      the inhibitory mechanism of the angiotensin receptor blocker olmesartan on
      albuminuria in a murine model of diabetic nephropathy. METHODS: Male db/db
      diabetic mice were fed with placebo or 20 mg/kg olmesartan by daily gavage for 12
      weeks. Conditionally immortalized mouse podocytes were treated with glucose,
      angiotensin II, olmesartan or p38 inhibitor s8307 in different experimental
      conditions after differentiation. RESULTS: Olmesartan reduced albuminuria in
      db/db mice without change in body weight and glycemia. The increase of apoptotic
      cells and decrease of podocytes in the diabetic glomerulus were prevented by
      olmesartan. Moreover, olmesartan restored silent mating type information
      regulation 1 (SIRT1) expression in diabetic glomeruli. Furthermore, olmesartan
      treatment suppressed p38 phosphorylation but did not restore adenosine 5'
      monophosphate-activated protein kinase (AMPK) phosphorylation in the diabetic
      glomerulus. In vitro study revealed that olmesartan prevented angiotensin
      II/p38/SIRT1 induced podocyte apoptosis, but it only slightly prevented high
      glucose/AMPK/SIRT1 induced podocyte apoptosis. In addition, the p38 inhibitor
      s8307 reversed SIRT1 expression and angiotensin II induced podocyte apoptosis.
      CONCLUSIONS: Olmesartan reduced albuminuria in diabetic nephropathy through
      inhibiting angiotensin II/p38/SIRT1 triggered podocyte apoptosis.

PMID- 27871085
TI  - Plasma Renalase is Not Associated with Blood Pressure and Brachial-Ankle Pulse
      Wave Velocity in Chinese Adults With Normal Renal Function.
AB  - BACKGROUND/AIMS: This study aimed to investigate the association of renalase with
      blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV) in order to
      better understand the role of renalase in the pathogenesis of hypertension and
      atherosclerosis. METHODS: A total of 344 subjects with normal kidney function
      were recruited from our previously established cohort in Shaanxi Province, China.
      They were divided into the normotensive (NT) and hypertensive (HT) groups or high
      baPWV and normal baPWV on the basis of BP levels or baPWV measured with an
      automatic waveform analyzer. Plasma renalase was determined through an enzyme
      linked immunosorbent assay. RESULTS: Plasma renalase did not significantly differ
      between HT and NT groups (3.71 +/- 0.69 ug/mL vs. 3.72 +/- 0.73 MUg/mL, P =
      0.905) and between subjects with and without high baPWV (3.67 +/- 0.66 ug/mL vs.
      3.73 +/- 0.74 ug/mL, P = 0.505). However, baPWV was significantly higher in the
      HT group than in the NT group (1460.4 +/- 236.7 vs. 1240.7 +/- 174.5 cm/s, P <
      0.001). Plasma renalase was not correlated with BP levels and baPWV in the entire
      group. Linear and logistic regression analysis revealed that plasma renalase was
      not significantly associated with hypertension and high baPWV. CONCLUSION: Plasma
      renalase may not be associated with BP and baPWV in Chinese subjects with normal
      renal function.

PMID- 27871086
TI  - The Influence of Two Different Foam Creams on Skin Barrier Repair of Foot
      Xerosis: A Prospective, Double-Blind, Randomised, Placebo-Controlled Intra
      Individual Study.
AB  - BACKGROUND/AIMS: Dry skin, or xerosis, is a common condition and a key feature of
      skin diseases like atopic dermatitis (AD) and ichthyosis vulgaris. Foot xerosis
      may exist without underlying disease and could be related to very mild forms of
      AD or ichthyosis vulgaris. The synthesis of important skin lipids (cholesterol,
      free fatty acids and ceramides) is reduced in xerosis and AD, and reduced lipid
      synthesis is responsible for a lack of lipids and enzymes in the skin barrier.
      This slows down reorganisation of the lipid lamellae in the stratum corneum (SC).
      METHODS: Skin barrier integrity was measured by morphometric analysis of the
      lipid lamellae in the SC after 4 weeks of treatment with a foam cream (active
      agent vs. placebo). RESULTS: Significant treatment effects were shown after 2 and
      4 weeks by an increasing amount of intercellular lipids in the SC. CONCLUSION:
      This study shows that a quick reorganisation of the SC lipids initiates a good
      restoration of the whole skin barrier after 4 weeks of treatment with a foam
      cream.

PMID- 27871087
TI  - The HDM2 (MDM2) Inhibitor NVP-CGM097 Inhibits Tumor Cell Proliferation and Shows
      Additive Effects with 5-Fluorouracil on the p53-p21-Rb-E2F1 Cascade in the
      p53wild type Neuroendocrine Tumor Cell Line GOT1.
AB  - BACKGROUND/AIMS: The tumor suppressor p53 is depleted in many tumor cells by the
      E3 ubiquitin ligase mouse double minute 2 homolog (MDM2) through MDM2/p53
      interaction. A novel target for inhibiting p53 degradation and for causing
      reexpression of p53wild type is inhibition of MDM2. The small molecule NVP-CGM097
      is a novel MDM2 inhibitor. We investigated MDM2 inhibition as a target in
      neuroendocrine tumor cells in vitro. METHODS: Human neuroendocrine tumor cell
      lines from the pancreas (BON1), lung (NCI-H727), and midgut (GOT1) were incubated
      with the MDM2 inhibitor NVP-CGM097 (Novartis) at concentrations from 4 to 2,500
      nM. RESULTS: While p53wild type GOT1 cells were sensitive to NVP-CGM097,
      p53mutated BON1 and p53mutated NCI-H727 cells were resistant to NVP-CGM097.
      Incubation of GOT1 cells with NVP-CGM097 at 100, 500, and 2,500 nM for 96 h
      caused a significant decline in cell viability to 84.9 +/- 9.2% (p < 0.05), 77.4
      +/- 6.6% (p < 0.01), and 47.7 +/- 9.2% (p < 0.01). In a Western blot analysis of
      GOT1 cells, NVP-CGM097 caused a dose-dependent increase in the expression of p53
      and p21 tumor suppressor proteins and a decrease in phospho-Rb and E2F1.
      Experiments of co-incubation of NVP-CGM097 with 5-fluorouracil, temozolomide, or
      everolimus each showed additive antiproliferative effects in GOT1 cells. NVP
      CGM097 and 5-fluorouracil increased p53 and p21 expression in an additive manner.
      CONCLUSIONS: MDM2 inhibition seems a promising novel therapeutic target in
      neuroendocrine tumors harboring p53wild type. Further investigations should
      examine the potential role of MDM2 inhibitors in neuroendocrine tumor treatment.

PMID- 27871089
TI  - Water balance creates a threshold in soil pH at the global scale.
AB  - Soil pH regulates the capacity of soils to store and supply nutrients, and thus
      contributes substantially to controlling productivity in terrestrial ecosystems.
      However, soil pH is not an independent regulator of soil fertility-rather, it is
      ultimately controlled by environmental forcing. In particular, small changes in
      water balance cause a steep transition from alkaline to acid soils across natural
      climate gradients. Although the processes governing this threshold in soil pH are
      well understood, the threshold has not been quantified at the global scale, where
      the influence of climate may be confounded by the effects of topography and
      mineralogy. Here we evaluate the global relationship between water balance and
      soil pH by extracting a spatially random sample (n = 20,000) from an extensive
      compilation of 60,291 soil pH measurements. We show that there is an abrupt
      transition from alkaline to acid soil pH that occurs at the point where mean
      annual precipitation begins to exceed mean annual potential evapotranspiration.
      We evaluate deviations from this global pattern, showing that they may result
      from seasonality, climate history, erosion and mineralogy. These results
      demonstrate that climate creates a nonlinear pattern in soil solution chemistry
      at the global scale; they also reveal conditions under which soils maintain pH
      out of equilibrium with modern climate.

PMID- 27871091
TI  - Age-Specific Injury Risk Curves for Distributed, Anterior Thoracic Loading of
      Various Sizes of Adults Based on Sternal Deflections.
AB  - Injury Risk Curves are developed from cadaver data for sternal deflections
      produced by anterior, distributed chest loads for a 25, 45, 55, 65 and 75 year
      old Small Female, Mid-Size Male and Large Male based on the variations of bone
      strengths with age. These curves show that the risk of AIS >= 3 thoracic injury
      increases with the age of the person. This observation is consistent with NASS
      data of frontal accidents which shows that older unbelted drivers have a higher
      risk of AIS >= 3 chest injury than younger drivers.

PMID- 27871088
TI  - Structure of photosystem II and substrate binding at room temperature.
AB  - Light-induced oxidation of water by photosystem II (PS II) in plants, algae and
      cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a
      membrane-bound multi-subunit pigment protein complex, couples the one-electron
      photochemistry at the reaction centre with the four-electron redox chemistry of
      water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC).
      Under illumination, the OEC cycles through five intermediate S-states (S0 to S4),
      in which S1 is the dark-stable state and S3 is the last semi-stable state before
      O-O bond formation and O2 evolution. A detailed understanding of the O-O bond
      formation mechanism remains a challenge, and will require elucidation of both the
      structures of the OEC in the different S-states and the binding of the two
      substrate waters to the catalytic site. Here we report the use of femtosecond
      pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room
      temperature structures of dark-adapted (S1), two-flash illuminated (2F; S3
      enriched), and ammonia-bound two-flash illuminated (2F-NH3; S3-enriched) PS II.
      Although the recent 1.95 A resolution structure of PS II at cryogenic temperature
      using an XFEL provided a damage-free view of the S1 state, measurements at room
      temperature are required to study the structural landscape of proteins under
      functional conditions, and also for in situ advancement of the S-states. To
      investigate the water-binding site(s), ammonia, a water analogue, has been used
      as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states. Since
      the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate
      water site. This approach, together with a comparison of the native dark and 2F
      states, is used to discriminate between proposed O-O bond formation mechanisms.

PMID- 27871093
TI  - Effect of Abdominal Loading Location on Liver Motion: Experimental Assessment
      using Ultrafast Ultrasound Imaging and Simulation with a Human Body Model.
AB  - A protocol based on ultrafast ultrasound imaging was applied to study the in situ
      motion of the liver while the abdomen was subjected to compressive loading at 3
      m/s by a hemispherical impactor or a seatbelt. The loading was applied to various
      locations between the lower abdomen and the mid thorax while feature points
      inside the liver were followed on the ultrasound movie (2000 frames per second).
      Based on tests performed on five post mortem human surrogates (including four
      tested in the current study), trends were found between the loading location and
      feature point trajectory parameters such as the initial angle of motion or the
      peak displacement in the direction of impact. The impactor tests were then
      simulated using the GHBMC M50 human body model that was globally scaled to the
      dimensions of each surrogate. Some of the experimental trends observed could be
      reproduced in the simulations (e.g. initial angle) while others differed more
      widely (e.g. final caudal motion). The causes for the discrepancies need to be
      further investigated. The liver strain energy density predicted by the model was
      also widely affected by the impact location. Experimental and simulation results
      both highlight the importance of the liver position with respect to the impactor
      when studying its response in situ.

PMID- 27871092
TI  - The Effect of Rib Shape on Stiffness.
AB  - This study investigates the isolated effect of rib shape on the mechanical
      characteristics of ribs subjected to multiple forms of loading. It aims to
      measure the variation in stiffness due to shape that is seen throughout the
      population and, in particular, provide a tool for researchers to better
      understand the influence of shape on resulting stiffness. A previously published
      six-parameter shape model of the central axis of human ribs was used. It has been
      shown to accurately model the overall rib path using intrinsic geometric
      properties such as size, aspect ratio, and skewness, through shapes based on
      logarithmic spirals with high curvature continuity. In this study the model was
      fitted to 19,500 ribs from 989 adult female and male CT scans having demographic
      distributions matching the US adult population. Mechanical loading was simulated
      through a simplified finite element model aimed at isolating rib shape from other
      factors influencing mechanical response. Four loading scenarios were used
      representing idealized free and constrained loading conditions in axial (body
      anterior) and lateral directions. Characteristic rib stiffness and maximum stress
      location were tracked as simulation output measures. Regression models of rib
      stiffness found that all shape model parameters added information when predicting
      stiffness under each loading condition, with their linear combination able to
      account for 95% of the population stiffness variation due to shape in midlevel
      ribs for free axial loading, and 92%-98% in other conditions. Full regression
      models including interactive terms explained up to 99% of population variability.
      Results allow researchers to better evaluate the differences in stiffness results
      that are obtained from physical testing by providing a framework with which to
      explain variation due to rib shape.

PMID- 27871094
TI  - Biomechanical Responses of PMHS Subjected to Abdominal Seatbelt Loading.
AB  - Past studies have found that a pressure based injury risk function was the best
      predictor of liver injuries due to blunt impacts. In an effort to expand upon
      these findings, this study investigated the biomechanical responses of the
      abdomen of post mortem human surrogates (PMHS) to high-speed seatbelt loading and
      developed external response targets in conjunction with proposing an abdominal
      injury criterion. A total of seven unembalmed PMHS, with an average mass and
      stature of 71 kg and 174 cm respectively were subjected to belt loading using a
      seatbelt pull mechanism, with the PMHS seated upright in a freeback
      configuration. A pneumatic piston pulled a seatbelt into the abdomen at the level
      of the umbilicus with a nominal peak penetration speed of 4.0 m/s. Pressure
      transducers were placed in the re-pressurized abdominal vasculature, including
      the inferior vena cava (IVC) and abdominal aorta, to measure internal pressure
      variation during the event. Jejunum tear, colon hemorrhage, omentum tear, splenic
      fracture and transverse processes fracture were identified during post-test
      anatomical dissection. Peak abdominal forces ranged from 2.8 to 4.7 kN. Peak
      abdominal penetrations ranged from 110 to 177 mm. A force-penetration corridor
      was developed from the PMHS tests in an effort to benchmark ATD biofidelity. Peak
      aortic pressures ranged from 30 to 104 kPa and peak IVC pressures ranged from 36
      to 65 kPa. Updated pressure based abdominal injury risk functions were developed
      for vascular Pmax and Pmax*Pmax.

PMID- 27871090
TI  - The genomic basis of circadian and circalunar timing adaptations in a midge.
AB  - Organisms use endogenous clocks to anticipate regular environmental cycles, such
      as days and tides. Natural variants resulting in differently timed behaviour or
      physiology, known as chronotypes in humans, have not been well characterized at
      the molecular level. We sequenced the genome of Clunio marinus, a marine midge
      whose reproduction is timed by circadian and circalunar clocks. Midges from
      different locations show strain-specific genetic timing adaptations. We examined
      genetic variation in five C. marinus strains from different locations and mapped
      quantitative trait loci for circalunar and circadian chronotypes. The region most
      strongly associated with circadian chronotypes generates strain-specific
      differences in the abundance of calcium/calmodulin-dependent kinase II.1
      (CaMKII.1) splice variants. As equivalent variants were shown to alter CaMKII
      activity in Drosophila melanogaster, and C. marinus (Cma)-CaMKII.1 increases the
      transcriptional activity of the dimer of the circadian proteins Cma-CLOCK and Cma
      CYCLE, we suggest that modulation of alternative splicing is a mechanism for
      natural adaptation in circadian timing.

PMID- 27871095
TI  - Investigation of Pelvic Injuries on Eighteen Post Mortem Human Subjects Submitted
      to Oblique Lateral Impacts.
AB  - The aim of this study was to investigate the sacroiliac joint injury mechanism.
      Two test configurations were selected from full scale car crashes conducted with
      the WorldSID 50th dummy resulting in high sacroiliac joint loads and low pubic
      symphysis force, i.e. severe conditions for the sacroiliac joint. The two test
      conditions were reproduced in laboratory using a 150-155 kg guided probe
      propelled respectively at 8 m/s and 7.5 m/s and with different shapes and
      orientations for the plate impacting the pelvis. Nine Post Mortem Human Subject
      (PMHS) were tested in each of the two configurations (eighteen PMHS in total). In
      order to get information on the time of fracture, eleven strain gauges were glued
      on the pelvic bone of each PMHS. Results - In the first configuration, five PMHS
      out of nine sustained AIS2+ pelvic injuries. All five presented sacroiliac joint
      injuries associated with pubic area injuries. In the second configuration, four
      specimens out of nine sustained AIS2+ pelvic injuries. Two of them presented
      sacroiliac joint fractures associated with pubic area injuries. The other two
      presented injuries at the pubic area and acetabulum only. The strain gauges
      signals suggested that the pubic fractures occurred before the sacroiliac joint
      fractures in the great majority of the cases (five cases out of seven).
      Conclusions - Even in the oblique impact conditions of the present study, the
      pubic symphysis area was observed to be the weakest zone of the pelvis and its
      failure the predominant cause of sacroiliac joint injuries. It was hypothesized
      that the failure of the pubic rami allowed the hemi-pelvis to rotate inward, and
      that this closing-book motion induced the failure of the sacroiliac joint.

PMID- 27871097
TI  - Association of Impact Velocity with Risks of Serious Injuries and Fatalities to
      Pedestrians in Commercial Truck-Pedestrian Accidents.
AB  - This study aimed to clarify the relationship between truck-pedestrian crash
      impact velocity and the risks of serious injury and fatality to pedestrians. We
      used micro and macro truck-pedestrian accident data from the Japanese Institute
      for Traffic Accident Research and Data Analysis (ITARDA) database. We classified
      vehicle type into five categories: heavy-duty trucks (gross vehicle weight [GVW]
      >=11 * 103 kg [11 tons (t)], medium-duty trucks (5 * 103 kg [5 t] <= GVW < 11 *
      103 kg [11 t]), light-duty trucks (GVW <5 * 103 kg [5 t]), box vans, and sedans.
      The fatality risk was <=5% for light-duty trucks, box vans, and sedans at impact
      velocities <= 30 km/h and for medium-duty trucks at impact velocities <=20 km/h.
      The fatality risk was <=10% for heavy-duty trucks at impact velocities <=10 km/h.
      Thus, fatality risk appears strongly associated with vehicle class. The results
      also revealed that a 10 km/h reduction in impact velocities could mitigate the
      severity of pedestrian injuries at impact velocities >=30 km/h for all five
      analyzed vehicle types. Therefore, serious injuries and fatalities to pedestrians
      could be decreased by the development and deployment of collision mitigation
      systems (CMSs) to all vehicles, including to commercial trucks, because CMSs can
      detect pedestrians in even severe conditions, such as when the drive's view is
      obstructed, and can reduce the impact velocity. The present results indicate that
      CMS design specifications should differ between vehicle types because of the
      strong dependence of seriousinjury and fatality risks on vehicle type.

PMID- 27871096
TI  - Responses and Injuries to PMHS in Side-Facing and Oblique Seats in Horizontal
      Longitudinal Sled Tests per FAA Emergency Landing Conditions.
AB  - The objective of the present exploratory study is to understand occupant
      responses in oblique and side-facing seats in the aviation environment, which are
      increasingly installed in modern aircrafts. Sled tests were conducted using
      intact Post Mortem Human Surrogates (PMHS) seated in custom seats approximating
      standard aircraft geometry. End conditions were selected to represent candidate
      aviation seat and restraint configurations. Three-dimensional head center-of
      gravity linear accelerations, head angular velocities, and linear accelerations
      of the T1, T6, and T12 spinous processes, and sacrum were obtained. Three
      dimensional kinematics relative to the seat were obtained from retroreflective
      targets attached to the head, T1, T6, T12, and sacrum. All specimens sustained
      spinal injuries, although variations existed by vertebral level. While the
      tension mechanism was associated with cervical spine injuries, complex
      distraction-coupled with bending and tension was attributed to thoracolumbar
      spine injuries. Skeletal fractures to the ribcage were attributed to compression
      induced by the restraint from the seatbelt, the presence of the armrest, and/or
      severe motions of the unconstrained torso. Pelvic injuries were also attributed
      to restraint offered by the lap belt on the accelerating torso-pelvis complex in
      the absence of the armrest. Lower extremity injuries occurred due to the
      unconstrained motion (flailing mechanism). These results serve as an initial
      dataset to understand the kinematics of different body regions, injuries and
      patterns, and potential injury mechanisms describing PMHS responses in the
      aviation environment.

PMID- 27871098
TI  - Traffic Accidents Involving Cyclists Identifying Causal Factors Using
      Questionnaire Survey, Traffic Accident Data, and Real-World Observation.
AB  - The purpose of this study is to clarify the mechanism of traffic accidents
      involving cyclists. The focus is on the characteristics of cyclist accidents and
      scenarios, because the number of traffic accidents involving cyclists in Tokyo is
      the highest in Japan. First, dangerous situations in traffic incidents were
      investigated by collecting data from 304 cyclists in one city in Tokyo using a
      questionnaire survey. The survey indicated that cyclists used their bicycles
      generally while commuting to work or school in the morning. Second, the study
      investigated the characteristics of 250 accident situations involving cyclists
      that happened in the city using real-world bicycle accident data. The results
      revealed that the traffic accidents occurred at intersections of local streets,
      where cyclists collided most often with vehicles during commute time in the
      morning. Third, cyclists' behavior was observed at a local street intersection in
      the morning in the city using video pictures. In one hour during the morning
      commute period, 250 bicycles passed through the intersection. The results
      indicated that one of the reasons for traffic accidents involving cyclists might
      be the combined effect of low visibility, caused by the presence of box-like
      building structures close to the intersections, and the cyclists' behavior in
      terms of their velocity and no confirming safety. It was observed that, on
      average, bicycle velocity was 3.1 m/s at the initial line of an intersection. The
      findings from this study could be useful in developing new technologies to
      improve cyclist safety, such as alert devices for cyclists and vehicle drivers,
      wireless communication systems between cyclists and vehicle drivers, or advanced
      vehicles with bicycle detection and collision mitigation systems.

PMID- 27871099
TI  - Evaluation of WIAMan Technology Demonstrator Biofidelity Relative to Sub
      Injurious PMHS Response in Simulated Under-body Blast Events.
AB  - Three laboratory simulated sub-injurious under-body blast (UBB) test conditions
      were conducted with whole-body Post Mortem Human Surrogates (PMHS) and the
      Warrior Assessment Injury Manikin (WIAMan) Technology Demonstrator (TD) to
      establish and assess UBB biofidelity of the WIAMan TD. Test conditions included a
      rigid floor and rigid seat with independently varied pulses. On the floor, peak
      velocities of 4 m/s and 6 m/s were applied with a 5 ms time to peak (TTP). The
      seat peak velocity was 4 m/s with varied TTP of 5 and 10 ms. Tests were conducted
      with and without personal protective equipment (PPE). PMHS response data was
      compiled into preliminary biofidelity response corridors (BRCs), which served as
      evaluation metrics for the WIAMan TD. Each WIAMan TD response was evaluated
      against the PMHS preliminary BRC for the loading and unloading phase of the
      signal time history using Correlation Analysis (CORA) software to assign a
      numerical score between 0 and 1. A weighted average of all responses was
      calculated to determine body region and whole body biofidelity scores for each
      test condition. The WIAMan TD received UBB biofidelity scores of 0.62 in
      Condition A, 0.59 in Condition B, and 0.63 in Condition C, putting it in the fair
      category (0.44-0.65). Body region responses with scores below a rating of good
      (0.65-0.84) indicate potential focus areas for the next generation of the WIAMan
      design.

PMID- 27871100
TI  - Biomechanical Response of Military Booted and Unbooted Foot-Ankle-Tibia from
      Vertical Loading.
AB  - A new anthropomorphic test device (ATD) is being developed by the US Army to be
      responsive to vertical loading during a vehicle underbody blast event. To obtain
      design parameters for the new ATD, a series of non-injurious tests were conducted
      to derive biofidelity response corridors for the foot-ankle complex under
      vertical loading. Isolated post mortem human surrogate (PMHS) lower leg specimens
      were tested with and without military boot and in different initial foot-ankle
      positions. Instrumentation included a six-axis load cell at the proximal end,
      three-axis accelerometers at proximal and distal tibia, and calcaneus, and strain
      gages. Average proximal tibia axial forces for a neutral-positioned foot were
      about 2 kN for a 4 m/s test, 4 kN for 6 m/s test and 6 kN for an 8 m/s test. The
      force time-to-peak values were from 3 to 5 msec and calcaneus acceleration rise
      times were 2 to 8 msec. Compared to the neutral posture, the "off-axis" measures
      (e.g. shear and bending moment) were much greater in magnitude in plantar- or
      dorsi-flexed posture. The results as a function of velocity demonstrated uniform
      increases with increasing test velocities. The response corridors supplied from
      the present investigation will serve as initial design parameters for the ATD
      lower leg, and can also be used for validation for a human computational model.

PMID- 27871101
TI  - Morphomics of the Talus.
AB  - Previous studies of frontal crash databases reported that ankle fractures are
      among the most common lower extremity fractures. While not generally life
      threatening, these injuries can be debilitating. Laboratory research into the
      mechanisms of ankle fractures has linked dorsiflexion with an increased risk of
      tibia and fibula malleolus fractures. However, talus fractures were not produced
      in the laboratory tests and appear to be caused by more complex loading of the
      joint. In this study, an analysis of the National Automotive Sampling System -
      Crashworthiness Data System (NASS-CDS) for the years 2004-2013 was conducted to
      investigate foot-ankle injury rates in front seat occupants involved in frontal
      impact crashes. A logistic regression model was developed indicating occupant
      weight, impact delta velocity and gender to be significant predictors of talus
      fracture (p<0.05). Separately, a specific set of Computed Tomography (CT) scans
      from the International Center for Automotive Medicine (ICAM) scan database was
      used to characterize the talar dome. This control population consisted of 207
      adults aged 18 to 84, with no foot or ankle trauma, and scans that had suitable
      coverage of the talus. Size of the talus was determined using medial-to-lateral
      width and anterior-to-posterior depth measurements. Geometry was assessed by
      evaluating the radius of the articulating talus and strength was assessed using a
      combination of cross sectional area and density. Demographics were studied to
      investigate correlation with talus measurements from the CT scan database. A
      multi-variable linear regression model of the morphomics showed gender to be
      statistically significant (p<0.05) for talus depth, width, cross-sectional area,
      radius and strength. Body Mass Index (BMI) was significant for depth and radius.
      Weight was significant for depth, width, density and strength. Stature was
      significant for depth, cross-sectional area, radius and strength. Age was
      significant for radius and density.

PMID- 27871102
TI  - New Risk Curves for NHTSA's Brain Injury Criterion (BrIC): Derivations and
      Assessments.
AB  - The National Highway Traffic Safety Administration (NHTSA) recently published a
      Request for Comments regarding a potential upgrade to the US New Car Assessment
      Program (US NCAP) - a star-rating program pertaining to vehicle crashworthiness.
      Therein, NHTSA (a) cited two metrics for assessing head risk: Head Injury
      Criterion (HIC15) and Brain Injury Criterion (BrIC), and (b) proposed to conduct
      risk assessment via its risk curves for those metrics, but did not prescribe a
      specific method for applying them. Recent studies, however, have indicated that
      the NHTSA risk curves for BrIC significantly overstate field-based head injury
      rates. Therefore, in the present three-part study, a new set of BrIC-based risk
      curves was derived, an overarching head risk equation involving risk curves for
      both BrIC and HIC15 was assessed, and some additional candidatepredictor-
      variable assessments were conducted. Part 1 pertained to the derivation.
      Specifically, data were pooled from various sources: Navy volunteers, amateur
      boxers, professional football players, simple-fall subjects, and racecar drivers.
      In total, there were 4,501 cases, with brain injury reported in 63. Injury
      outcomes were approximated on the Abbreviated Injury Scale (AIS). The statistical
      analysis was conducted subject to ordinal logistic regression analysis (OLR),
      such that the various levels of brain injury were cast as a function of BrIC. The
      resulting risk curves, with Goodman Kruksal Gamma=0.83, were significantly
      different than those from NHTSA. Part 2 pertained to the assessment relative to
      field data. Two perspectives were considered: "aggregate" (DeltaV=0-56 km/h) and
      "point" (high-speed, regulatory focus). For the aggregate perspective, the new
      risk curves for BrIC were applied in field models pertaining to belted, mid-size,
      adult drivers in 11-1 o'clock, full-engagement frontal crashes in the National
      Automotive Sampling System (NASS, 1993-2014 calendar years). For the point
      perspective, BrIC data from tests were used. The assessments were conducted for
      minor, moderate, and serious injury levels for both Newer Vehicles (airbag
      fitted) and Older Vehicles (not airbag-fitted). Curve-based injury rates and NASS
      based injury rates were compared via average percent difference (AvgPctDiff). The
      new risk curves demonstrated significantly better fidelity than those from NHTSA.
      For example, for the aggregate perspective (n=12 assessments), the results were
      as follows: AvgPctDiff (present risk curves) = +67 versus AvgPctDiff (NHTSA risk
      curves) = +9378. Part 2 also contained a more comprehensive assessment.
      Specifically, BrIC-based risk curves were used to estimate brain-related injury
      probabilities, HIC15-based risk curves from NHTSA were used to estimate
      bone/other injury probabilities, and the maximum of the two resulting
      probabilities was used to represent the attendant headinjury probabilities.
      (Those HIC15-based risk curves yielded AvgPctDiff=+85 for that application.)
      Subject to the resulting 21 assessments, similar results were observed:
      AvgPctDiff (present risk curves) = +42 versus AvgPctDiff (NHTSA risk curves) =
      +5783. Therefore, based on the results from Part 2, if the existing BrIC metric
      is to be applied by NHTSA in vehicle assessment, we recommend that the
      corresponding risk curves derived in the present study be considered. Part 3
      pertained to the assessment of various other candidate brain-injury metrics.
      Specifically, Parts 1 and 2 were revisited for HIC15, translation acceleration
      (TA), rotational acceleration (RA), rotational velocity (RV), and a different
      rotational brain injury criterion from NHTSA (BRIC). The rank-ordered results for
      the 21 assessments for each metric were as follows: RA, HIC15, BRIC, TA, BrIC,
      and RV. Therefore, of the six studied sets of OLR-based risk curves, the set for
      rotational acceleration demonstrated the best performance relative to NASS.

PMID- 27871103
TI  - Development of an Unbiased Validation Protocol to Assess the Biofidelity of
      Finite Element Head Models used in Prediction of Traumatic Brain Injury.
AB  - This study describes a method to identify laboratory test procedures and impact
      response requirements suitable for assessing the biofidelity of finite element
      head models used in prediction of traumatic brain injury. The selection of the
      experimental data and the response requirements were result of a critical
      evaluation based on the accuracy, reproducibility and relevance of the available
      experimental data. A weighted averaging procedure was chosen in order to consider
      different contributions from the various test conditions and target measurements
      based on experimental error. According to the quality criteria, 40 experimental
      cases were selected to be a representative dataset for validation. Based on the
      evaluation of response curves from four head finite element models, CORA was
      chosen as a quantitative method to compare the predicted time history response to
      the measured data. Optimization of the CORA global settings led to the
      recommendation of performing curve comparison on a fixed time interval of 0-30 ms
      for intracranial pressure and at least 0-40 ms for brain motion and deformation.
      The allowable maximum time shift was adjusted depending on the shape of the
      experimental curves (DMAX = 0.12 for intracranial pressure, DMAX = 0.40 for brain
      motion and DMAX = 0.25 for brain deformation). Finally, bigger penalization of
      ratings was assigned to curves with fundamentally incorrect shape compared to
      those having inaccuracies in amplitude or time shift (cubic vs linear). This
      rigorous approach is necessary to ensure confidence in the model results and
      progress in the usage of finite element head models for traumatic brain injury
      prediction.

PMID- 27871104
TI  - Development, Evaluation, and Sensitivity Analysis of Parametric Finite Element
      Whole-Body Human Models in Side Impacts.
AB  - Occupant stature and body shape may have significant effects on injury risks in
      motor vehicle crashes, but the current finite element (FE) human body models
      (HBMs) only represent occupants with a few sizes and shapes. Our recent studies
      have demonstrated that, by using a mesh morphing method, parametric FE HBMs can
      be rapidly developed for representing a diverse population. However, the
      biofidelity of those models across a wide range of human attributes has not been
      established. Therefore, the objectives of this study are 1) to evaluate the
      accuracy of HBMs considering subject-specific geometry information, and 2) to
      apply the parametric HBMs in a sensitivity analysis for identifying the specific
      parameters affecting body responses in side impact conditions. Four side-impact
      tests with two male post-mortem human subjects (PMHSs) were selected to evaluate
      the accuracy of the geometry and impact responses of the morphed HBMs. For each
      PMHS test, three HBMs were simulated to compare with the test results: the
      original Total Human Model for Safety (THUMS) v4.01 (O-THUMS), a parametric THUMS
      (P-THUMS), and a subject-specific THUMS (S-THUMS). The P-THUMS geometry was
      predicted from only age, sex, stature, and BMI using our statistical geometry
      models of skeleton and body shape, while the S-THUMS geometry was based on each
      PMHS's CT data. The simulation results showed a preliminary trend that the
      correlations between the PTHUMS- predicted impact responses and the four PMHS
      tests (mean-CORA: 0.84, 0.78, 0.69, 0.70) were better than those between the O
      THUMS and the normalized PMHS responses (mean-CORA: 0.74, 0.72, 0.55, 0.63),
      while they are similar to the correlations between S-THUMS and the PMHS tests
      (mean-CORA: 0.85, 0.85, 0.67, 0.72). The sensitivity analysis using the PTHUMS
      showed that, in side impact conditions, the HBM skeleton and body shape
      geometries as well as the body posture were more important in modeling the
      occupant impact responses than the bone and soft tissue material properties and
      the padding stiffness with the given parameter ranges. More investigations are
      needed to further support these findings.

PMID- 27871105
TI  - Development and Full Body Validation of a 5th Percentile Female Finite Element
      Model.
AB  - To mitigate the societal impact of vehicle crash, researchers are using a variety
      of tools, including finite element models (FEMs). As part of the Global Human
      Body Models Consortium (GHBMC) project, comprehensive medical image and
      anthropometrical data of the 5th percentile female (F05) were acquired for the
      explicit purpose of FEM development. The F05-O (occupant) FEM model consists of
      981 parts, 2.6 million elements, 1.4 million nodes, and has a mass of 51.1 kg.
      The model was compared to experimental data in 10 validation cases ranging from
      localized rigid hub impacts to full body sled cases. In order to make direct
      comparisons to experimental data, which represent the mass of an average male,
      the model was compared to experimental corridors using two methods: 1) post-hoc
      scaling the outputs from the baseline F05-O model and 2) geometrically morphing
      the model to the body habitus of the average male to allow direct comparisons.
      This second step required running the morphed full body model in all 10
      simulations for a total of 20 full body simulations presented. Overall,
      geometrically morphing the model was found to more closely match the target data
      with an average ISO score for the rigid impacts of 0.76 compared to 0.67 for the
      scaled responses. Based on these data, the morphed model was then used for model
      validation in the vehicle sled cases. Overall, the morphed model attained an
      average weighted score of 0.69 for the two sled impacts. Hard tissue injuries
      were also assessed and the baseline F05-O model was found to predict a greater
      occurrence of pelvic fractures compared to the GHBMC average male model, but
      predicted fewer rib fractures.

PMID- 27871106
TI  - Thoracic Injury Risk Curves for Rib Deflections of the SID-IIs Build Level D.
AB  - Injury risk curves for SID-IIs thorax and abdomen rib deflections proposed for
      future NCAP side impact evaluations were developed from tests conducted with the
      SID-IIs FRG. Since the floating rib guide is known to reduce the magnitude of the
      peak rib deflections, injury risk curves developed from SID-IIs FRG data are not
      appropriate for use with SID-IIs build level D. PMHS injury data from three
      series of sled tests and one series of whole-body drop tests are paired with
      thoracic rib deflections from equivalent tests with SID-IIs build level D. Where
      possible, the rib deflections of SID-IIs build level D were scaled to adjust for
      differences in impact velocity between the PMHS and SID-IIs tests. Injury risk
      curves developed by the Mertz-Weber modified median rank method are presented and
      compared to risk curves developed by other parametric and non-parametric methods.

PMID- 27871107
TI  - The Large Omnidirectional Child (LODC) ATD: Biofidelity Comparison with the
      Hybrid III 10 Year Old.
AB  - When the Hybrid III 10-year old (HIII-10C) anthropomorphic test device (ATD) was
      adopted into Code of Federal Regulations (CFR) 49 Part 572 as the best available
      tool for evaluating large belt-positioning booster seats in Federal Motor Vehicle
      Safety Standard (FMVSS) No. 213, NHTSA stated that research activities would
      continue to improve the performance of the HIII-10C to address biofidelity
      concerns. A significant part of this effort has been NHTSA's in-house development
      of the Large Omnidirectional Child (LODC) ATD. This prototype ATD is comprised of
      (1) a head with pediatric mass properties, (2) a neck that produces head lag with
      Zaxis rotation at the atlanto-occipital joint, (3) a flexible thoracic spine, (4)
      multi-point thoracic deflection measurement capability, (5) skeletal
      anthropometry representative of a seated child, and (6) an abdomen that can
      directly measure belt loading. The objective of this study was to evaluate the
      LODC by comparing its body region and full-body responses to both standard HIII
      10C responses and pediatric biomechanical data. In body region tests, the LODC
      (BioRank = 1.21) showed improved biofidelity over the HIII-10C (BioRank = 2.70).
      The LODC also exhibited kinematics more similar to pediatric PMHS kinematics in a
      reconstruction test. In FMVSS No. 213 tests, the LODC was observed to have lower
      HIC values with the absence of hard chin-to-chest contacts, indicating that chin
      to-chest contact severity is mitigated in the LODC design. LODC abdomen pressures
      and belt penetrations discriminated between restraint conditions. These results
      suggest the LODC has biofidelic characteristics that make it a candidate for
      improved assessment of injury risk in restraint system development.

PMID- 27871108
TI  - Biomechanical and Scaling Basis for Frontal and Side Impact Injury Assessment
      Reference Values.
AB  - In 1983, General Motors Corporation (GM) petitioned the National Highway Traffic
      Safety Administration (NHTSA) to allow the use of the biofidelic Hybrid III
      midsize adult male dummy as an alternate test device for FMVSS 208 compliance
      testing of frontal impact, passive restraint systems. To support their petition,
      GM made public to the international automotive community the limit values that
      they imposed on the Hybrid III measurements, which were called Injury Assessment
      Reference Values (IARVs). During the past 20 years, these IARVs have been updated
      based on relevant biomechanical studies that have been published and scaled to
      provide IARVs for the Hybrid III and CRABI families of frontal impact dummies.
      Limit values have also been developed for the biofidelic side impact dummies,
      BioSID, ES-2 and SID-IIs. The purpose of the original publication was to provide
      in a single document: 1) a listing of the IARVs for measurements made with the
      Hybrid III and CRABI families of frontal impact dummies, and for the biofidelic
      side impact dummies, 2) the biomechanical and/or scaling bases for these IARVs,
      and 3) a comparison of IARVs and regulatory compliance limits and how they affect
      restraint design. The purpose for republication is to correct errors in the
      original publication and update the regulatory compliance limits.

PMID- 27871109
TI  - [Graves' Orbitopathy].

PMID- 27871110
TI  - [Understanding OCT - Part 2: State of the Practice].

PMID- 27871111
TI  - [Understanding OCT - Part 1: Basic Knowledge].

PMID- 27871112
TI  - PRKACA Mutations in Adrenal Adenomas: Genotype/Phenotype Correlations.
AB  - Untargeted, next generation sequencing approaches have provided deep insights
      into genetic events that result in unopposed steroidogenesis from the adrenal
      cortex. In particular, somatic mutations in the gene encoding the catalytic
      subunit alpha of protein kinase A (PKA) (PRKACA) were identified independently by
      several groups as the most frequently altered gene in cortisol-producing
      adenomas. Detailed functional studies could explore the molecular consequences of
      these hot-spot mutations and large international cohorts have provided the basis
      to explore the clinical characteristics associated with this mutation. Thereby,
      PRKACA mutations are highly specific for cortisol over-secretion, while they are
      absent or very rare in the context of other adrenal diseases. Patients carrying
      these somatic mutations are affected by a more severe phenotype and are
      identified at a younger age. Thus, these genotype/phenotype correlations provide
      further evidence for the importance of PKA-dependent pathways for adrenal
      physiology and disease.

PMID- 27871113
TI  - Bone Formation, Growth, and Repair.

PMID- 27871114
TI  - Bone Marrow Stromal Stem Cells in Tissue Engineering and Regenerative Medicine.
AB  - Bone marrow stromal stem cells (BMSCs) are adult multipotent cells, which have
      the potential to differentiate into cell types of mesodermal origin, namely
      osteocytes, adipocytes, and chondrocytes. Due to their accessibility and
      expansion potential, BMSCs have historically held therapeutic promise in tissue
      engineering and regenerative medicine applications. More recently, it has been
      demonstrated that not only can bone marrow stromal stem cells directly
      participate in tissue regeneration, but they also have the capacity to migrate to
      distant sites of tissue injury, where they can participate in tissue repair
      either directly through their differentiation or indirectly through paracrine
      mechanisms. Additionally, they can elicit various immunomodulatory signals, which
      can attenuate the inflammatory and immune responses. As such, bone marrow stromal
      stem cells have been explored clinically for treatment of a wide variety of
      different conditions including bone defects, graft-vs.-host disease,
      cardiovascular diseases, autoimmune diseases, diabetes, neurological diseases,
      and liver and kidney diseases. This review provides an overview of current
      clinical applications of bone marrow stromal stem cells and discusses their
      therapeutic properties, while also addressing limitations of their use. PubMed,
      Ovid, and Google Scholar online databases were searched using several keywords,
      including "stem cells", "tissue engineering", tissue regeneration" and "clinical
      trials". Additionally, Clinical trials.gov was used to locate completed clinical
      trials using bone marrow derived stem cells.

PMID- 27871115
TI  - Abnormal Proteoglycan Synthesis Due to Gene Defects Causes Skeletal Diseases with
      Overlapping Phenotypes.
AB  - In recent years, massively parallel sequencing technologies have helped us to
      identify novel disease genes and solve the mysteries behind rare diseases. Today,
      we know that some diseases with many overlapping and distinct clinical features,
      as presented in this review, can be caused by mutations in genes that encode
      enzymes playing crucial roles at different steps of the exact same pathway. In
      this review, we exclusively focused on 5 genes - XYLT1, XYLT2, B4GALT7, B3GALT6,
      and B3GAT3 - that encode enzymes involved in the biosynthesis of the common
      tetrasaccharide linker region of proteoglycans and review the associated
      diseases, also referred to as linkeropathies, by summarizing the cases reported
      in literature. Since proteoglycans are essential macromolecules in development,
      signaling and homeostasis of many tissues and organs, mutations in these genes
      can affect many organs; including bone, cartilage, eyes, ears, heart, and skin.
      Short stature, developmental delay, facial dysmorphism, and skeletal dysplasias
      are some of the common features observed in patients with mutations in these
      genes. Among these genes, XYLT2 mutations cause a relatively distinct phenotype,
      the so-called spondyloocular syndrome, which is characterized by clinical
      presentation of a very severe childhood-onset primary osteoporosis, cataract, and
      hearing impairment. The full phenotype spectrum of diseases mentioned here is
      likely to expand with additional clinical reports and further molecular studies.

PMID- 27871116
TI  - Glucocorticoid Signaling and Bone Biology.
AB  - Since glucocorticoids remain an effective therapeutic option for the treatment of
      many inflammatory and autoimmune diseases, glucocorticoid-induced osteoporosis is
      the most common form of secondary osteoporosis. Fractures may occur in as many as
      30-50% of patients receiving chronic glucocorticoid therapy. Under physiological
      conditions, glucocorticoids are required for normal bone development due to their
      regulation of osteoblast differentiation, possibly via the Wnt/beta-catenin
      pathway and TSC22D3. However, serum levels of endogenous corticosterone are
      elevated in aged mice and glucocorticoids exert negative effects on the survival
      of osteoblasts and osteocytes as well as angiogenesis. Glucocorticoid treatments
      impair bone formation and enhance bone resorption. Excess glucocorticoids induce
      osteoblast and osteocyte apoptosis by increasing pro-apoptotic molecules,
      reactive oxygen species, and endoplasmic reticulum stress and suppressing the
      Wnt/beta-catenin pathway. Autophagy protects osteocytes from glucocorticoid
      induced apoptosis, but passed some threshold, the process of autophagy leads the
      cells to apoptosis. Excess glucocorticoids impair osteoblastogenesis by inducing
      Wnt antagonists, including Dkk1, Sost, and sFRP-1. However, the findings are
      controversial and the involvement of Wnt antagonists requires further study.
      Excess glucocorticoids reduce the phosphorylation of Akt and GSK3beta, which
      enhances the degradation of beta-catenin. Excess glucocorticoids have been shown
      to modulate the expression of miRNAs, including miR-29a, miR-34a-5p, and miR-199a
      5p, which regulate the proliferation and differentiation of osteoblast lineage
      cells. Excess glucocorticoids also enhance bone resorption by reducing OPG
      expression, increasing Rankl expression and reactive oxygen species, and
      prolonging the life span of osteoclasts; however, they also suppress the bone
      degrading capacity of osteoclasts by disturbing the organization of the
      cytoskeleton.

PMID- 27871117
TI  - Hypoglycemic Activity of Polysaccharides from Sweet Corncob on Streptozotocin
      Induced Diabetic Rats.
AB  - A water-soluble polysaccharide (SCP-80-I) was isolated from sweet corncob using
      microwave-assisted compound-enzyme extraction and column chromatography. SCP-80-I
      is composed mainly of arabinose, mannose, glucose, and galactose in a molar ratio
      of 0.369:0.824:10.759:0.333, and has a molecular mass of 18350 Da and beta
      glycosides linkages in its molecular structure. The preliminary hypoglycemic and
      hypolipidemic activity in streptozotocin-induced diabetic rats was investigated.
      Rats were administered daily with 100, 200, and 400 mg/kg SCP-80-I for 21 d. The
      SCP-80-I increased the rat body mass significantly and reduced the blood glucose
      level in a dose-dependent manner. The SCP-80-I reduced liver swelling; kidney and
      pancreas hypertrophy; and total cholesterol, triglyceride, and low-density
      lipoprotein-C levels significantly; and increased the level of high-density
      lipoproteins in streptozotocin-induced diabetic rats. These results indicate that
      SCP-80-I exerts a potential hypoglycemic effect in streptozotocin-induced
      diabetic rats.

PMID- 27871118
TI  - Earlier nesting by generalist predatory bird is associated with human responses
      to climate change.
AB  - Warming temperatures cause temporal changes in growing seasons and prey abundance
      that drive earlier breeding by birds, especially dietary specialists within
      homogeneous habitat. Less is known about how generalists respond to climate
      associated shifts in growing seasons or prey phenology, which may occur at
      different rates across land cover types. We studied whether breeding phenology of
      a generalist predator, the American kestrel (Falco sparverius), was associated
      with shifts in growing seasons and, presumably, prey abundance, in a mosaic of
      non-irrigated shrub/grasslands and irrigated crops/pastures. We examined the
      relationship between remotely-sensed normalized difference vegetation index
      (NDVI) and abundance of small mammals that, with insects, constitute
      approximately 93% of kestrel diet biomass. We used NDVI to estimate the start of
      the growing season (SoGS) in irrigated and non-irrigated lands from 1992 to 2015
      and tested whether either estimate of annual SoGS predicted the timing of kestrel
      nesting. Finally, we examined relationships among irrigated SoGS, weather and
      crop planting. NDVI was a useful proxy for kestrel prey because it predicted
      small mammal abundance and past studies showed that NDVI predicts insect
      abundance. NDVI-estimated SoGS advanced significantly in irrigated lands (beta = 
      1.09 +/- 0.30 SE) but not in non-irrigated lands (beta = -0.57 +/- 0.53). Average
      date of kestrel nesting advanced 15 days in the past 24 years and was positively
      associated with the SoGS in irrigated lands, but not the SoGS in non-irrigated
      lands. Advanced SoGS in irrigated lands was related to earlier planting of crops
      after relatively warm winters, which were more common in recent years. Despite
      different patterns of SoGS change between land cover types, kestrel nesting
      phenology shifted with earlier prey availability in irrigated lands. Kestrels may
      preferentially track prey in irrigated lands over non-irrigated lands because of
      higher quality prey on irrigated lands, or earlier prey abundance may release
      former constraints on other selective pressures to breed early, such as seasonal
      declines in fecundity or competition for high-quality mates. This is one of the
      first examples of an association between human adaptation to climate change and
      shifts in breeding phenology of wildlife.

PMID- 27871119
TI  - Inhibitory Activity of Avocado Seed Fatty Acid Derivatives (Acetogenins) Against
      Listeria Monocytogenes.
AB  - High standards regarding Listeria monocytogenes control and consumer demands for
      food products without synthetic additives represent a challenge to food industry.
      We determined the antilisterial properties of an enriched acetogenin extract
      (EAE) from avocado seed, compared it to two commercial antimicrobials (one
      enriched in avocado acetogenins), and tested purified molecules. Acetogenin
      composition in pulp and seed of Hass avocado was quantified. EAE were obtained by
      two sequential centrifuge partition chromatography separations and molecules
      purified by preparative chromatography and quantified by HPLC-MS-TOF and HPLC
      PDA. Avocado seed extracts which are the following two: 1) EAE and 2) the
      commercially available antimicrobial Avosafe(r), presented similar inhibition
      zones and chemical profiles. Minimum inhibitory concentration (MIC) values of
      extracts and two isolated acetogenins varied between 7.8 and 15.6 mg/L, were
      effective at 37 and 4  degrees C, and showed a bactericidal effect probably
      caused by increased membrane permeability and lytic effects, evidenced by flow
      cytometry at 10 and 100* MIC. Activity was comparable to Mirenat(r). Most potent
      acetogenins were Persenone C (5) and A (6), and AcO-avocadenyne (1), the latter
      exclusively present in seed. Common features of bioactive molecules were the
      acetyl moiety and multiple unsaturations (2 to 3) in the aliphatic chain, some
      persenones also featured a trans-enone group. Seeds contained 1.6 times higher
      levels of acetogenins than pulp (5048.1 +/- 575.5 and 3107.0 +/- 207.2 mg/kg
      fresh weight, respectively), and total content in pulp was 199 to 398 times
      higher than MIC values. Therefore, acetogenin levels potentially consumed by
      humans are higher than inhibitory concentrations. Results document properties of
      avocado seed acetogenins as natural antilisterial food additives.

PMID- 27871120
TI  - Tri-focal Model of Care Implementation: Perspectives of Residents and Family.
AB  - PURPOSE: To explore residents' and family members' perceptions of partnership
      centered long-term care (LTC) associated with implementation of the Tri-focal
      Model of Care. The Model promotes partnership-centered care, evidence-based
      practice, and a positive environment. Its implementation is supported by a
      specifically designed education program. METHODS: The Model was implemented over
      approximately 12 months in seven LTC facilities in Victoria, Australia. A
      qualitative exploratory-descriptive approach was used. Data were collected using
      individual and focus group interviews with residents and family members prior to
      and following implementation of the Model. Data were analyzed thematically.
      FINDINGS: Prior to implementation of the Model, residents described experiencing
      a sense of disempowerment, and emphasized the importance of communication,
      engagement, and being a partner in the staff-resident care relationship.
      Following implementation, residents reported experiencing improved partnership
      approaches to care, although there were factors that impacted on having a good
      experience. Family members described a desire to remain involved in the
      resident's life by establishing good communication and rapport with staff. They
      acknowledged this was important for partnership-centered care. Following
      implementation, they described experiencing a partnership with staff, giving them
      confidence to assist staff and be included in decisions about the resident.
      CONCLUSIONS: The Tri-focal Model of Care can enable residents, family members,
      and staff to be partners in resident care in LTC settings. CLINICAL RELEVANCE:
      With an ageing population, an increasing demand for complex, individualized LTC
      exists. Delivery of high-quality LTC requires a strategy to implement a
      partnership-centered approach, involving residents, family members, and staff.

PMID- 27871121
TI  - High-Throughput Sequencing of Viable Microbial Communities in Raw Pork Subjected
      to a Fast Cooling Process.
AB  - This study aimed to investigate the effect of the fast cooling process on the
      microbiological community in chilled fresh pork during storage. We established a
      culture-independent method to study viable microbes in raw pork. Tray-packaged
      fresh pork and chilled fresh pork were completely spoiled after 18 and 49 d in
      aseptic bags at 4  degrees C, respectively. 16S/18S ribosomal RNAs were reverse
      transcribed to cDNA to characterize the activity of viable bacteria/fungi in the
      2 types of pork. Both cDNA and total DNA were analyzed by high-throughput
      sequencing, which revealed that viable Bacteroides sp. were the most active genus
      in rotten pork, although viable Myroides sp. and Pseudomonas sp. were also
      active. Moreover, viable fungi were only detected in chilled fresh pork. The
      sequencing results revealed that the fast cooling process could suppress the
      growth of microbes present initially in the raw meat to extend its shelf life.
      Our results also suggested that fungi associated with pork spoilage could not
      grow well in aseptic tray-packaged conditions.

PMID- 27871123
TI  - A Focus on Quality and Safety Traits of Saccharomyces cerevisiae Isolated from
      Uva di Troia Grape Variety.
AB  - The aim of this work was to study Saccharomyces cerevisiae strains isolated from
      vineyards of the autochthonous grape variety "Uva di Troia" located in different
      geographical areas of Apulian region (Southern Italy). Four hundred isolates were
      studied in relation to H2 S production, beta-glucosidase activity, and pigments
      adsorption from grape skin. Thus, 81 isolates were selected, identified through
      the amplification of the interdelta region, and grouped in 19 biotypes (from I to
      XIX). The enological performances were assessed to determine the content of
      residual sugars, ethanol, glycerol, and volatile acidity, after a
      microfermentation in Uva di Troia must for each isolate. The ability to remove
      ochratoxin A (OTA) was studied as an additional tool to select promising strains.
      A geographical-dependent technological variability was found for glycerol and
      volatile acidity, suggesting that the different indigenous yeasts can have a
      peculiar impact on the final characteristics of the corresponding wine ("Nero di
      Troia"). Only 2 biotypes (VI and XVII) were able to remove OTA throughout
      fermentation, with the highest reduction achieved by the biotype XVII (ca. 30%).

PMID- 27871122
TI  - Efficacy and safety of ablation for people with non-paroxysmal atrial
      fibrillation.
AB  - BACKGROUND: The optimal rhythm management strategy for people with non-paroxysmal
      (persistent or long-standing persistent) atrial fibrilation is currently not well
      defined. Antiarrhythmic drugs have been the mainstay of therapy. But recently, in
      people who have not responded to antiarrhythmic drugs, the use of ablation
      (catheter and surgical) has emerged as an alternative to maintain sinus rhythm to
      avoid long-term atrial fibrillation complications. However, evidence from
      randomised trials about the efficacy and safety of ablation in non-paroxysmal
      atrial fibrillation is limited. OBJECTIVES: To determine the efficacy and safety
      of ablation (catheter and surgical) in people with non-paroxysmal (persistent or
      long-standing persistent) atrial fibrillation compared to antiarrhythmic drugs.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE Ovid, Embase Ovid, conference abstracts, clinical trial
      registries, and Health Technology Assessment Database. We searched these
      databases from their inception to 1 April 2016. We used no language restrictions.
      SELECTION CRITERIA: We included randomised trials evaluating the effect of
      radiofrequency catheter ablation (RFCA) or surgical ablation compared with
      antiarrhythmic drugs in adults with non-paroxysmal atrial fibrillation,
      regardless of any concomitant underlying heart disease, with at least 12 months
      of follow-up. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected studies and extracted data. We evaluated risk of bias using the Cochrane
      'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous data with
      95% confidence intervals (CIs) a using fixed-effect model when heterogeneity was
      low (I2 <= 40%) and a random-effects model when heterogeneity was moderate or
      substantial (I2 > 40%). Using the GRADE approach, we evaluated the quality of the
      evidence and used the GRADE profiler (GRADEpro) to import data from Review
      Manager 5 to create 'Summary of findings' tables. MAIN RESULTS: We included three
      randomised trials with 261 participants (mean age: 60 years) comparing RFCA (159
      participants) to antiarrhythmic drugs (102) for non-paroxysmal atrial
      fibrillation. We generally assessed the included studies as having low or unclear
      risk of bias across multiple domains, with reported outcomes generally lacking
      precision due to low event rates. Evidence showed that RFCA was superior to
      antiarrhythmic drugs in achieving freedom from atrial arrhythmias (RR 1.84, 95%
      CI 1.17 to 2.88; 3 studies, 261 participants; low-quality evidence), reducing the
      need for cardioversion (RR 0.62, 95% CI 0.47 to 0.82; 3 studies, 261
      participants; moderate-quality evidence), and reducing cardiac-related
      hospitalisation (RR 0.27, 95% CI 0.10 to 0.72; 2 studies, 216 participants; low
      quality evidence) at 12 months follow-up. There was substantial uncertainty
      surrounding the effect of RFCA regarding significant bradycardia (or need for a
      pacemaker) (RR 0.20, 95% CI 0.02 to 1.63; 3 studies, 261 participants; low
      quality evidence), periprocedural complications, and other safety outcomes (RR
      0.94, 95% CI 0.16 to 5.68; 3 studies, 261 participants; very low-quality
      evidence). AUTHORS' CONCLUSIONS: In people with non-paroxysmal atrial
      fibrillation, evidence suggests a superiority of RFCA to antiarrhythmic drugs in
      achieving freedom from atrial arrhythmias, reducing the need for cardioversion,
      and reducing cardiac-related hospitalisations. There was uncertainty surrounding
      the effect of RFCA with significant bradycardia (or need for a pacemaker),
      periprocedural complications, and other safety outcomes. Evidence should be
      interpreted with caution, as event rates were low and quality of evidence ranged
      from moderate to very low.

PMID- 27871124
TI  - Introducing Technology for Thriving in Residential Long-Term Care.
AB  - PURPOSE: To present an emerging innovative care model that supports participation
      and thriving by older adults in residential care, by introduction to new
      technology and mobilizing volunteer services. DESIGN: Qualitative, exploratory
      study, introducing tablet computers to 15 older adults in two municipalities.
      METHODS: The intervention encompassed weekly workshops over the course of 1 year
      with volunteer adolescents as personal tutors. Observations of workshops,
      interviews with nurses, and repeated semistructured interviews with older adult
      participants eliciting their perspective on use, experiences, perceived
      usefulness, and overall evaluation of the intervention. FINDINGS: A model of four
      components is suggested to support participation and thriving by older adults in
      residential care: (a) simplified tools: iPad-technology relatively easy to use;
      (b) person-centered process: one-to-one tutoring following each individual's own
      pace; (c) young volunteers to teach technology, establishing an intergenerational
      arena; and (d) being mindful of driving forces that encourage use and learning.
      We found that all kinds of use and all levels of mastery generated a sense of
      pride that supported thriving and enjoyment. CONCLUSIONS: These findings support
      the use of new technology and use of volunteer services for sustaining thriving
      in older adults. The person-centered approach stimulates use of the tablet, and
      participants showed enjoyment, more social participation, and reported subjective
      experiences of thriving. CLINICAL RELEVANCE: Innovative models of care that
      prevent (or postpone) functional decline and support thriving in older adults are
      highly sought after in health care. A model that systematically involves
      volunteer services comes with potentials to alleviate nurses' workload, and then
      the intervention is seen as a manageable and low-cost initiative in residential
      care.

PMID- 27871125
TI  - Eye of the Finch: characterization of the ocular microbiome of house finches in
      relation to mycoplasmal conjunctivitis.
AB  - Vertebrate ocular microbiomes are poorly characterized and virtually unexplored
      in wildlife species. Pathogen defense is considered a key function of
      microbiomes, but determining microbiome stability during disease is critical for
      understanding the role of resident microbial communities in infectious disease
      dynamics. Here, we characterize the ocular bacterial microbiome of house finches
      (Haemorhous mexicanus), prior to and during experimental infection with an
      inflammatory ocular disease, Mycoplasmal conjunctivitis, caused by Mycoplasma
      gallisepticum. In ocular tissues of healthy house finches, we identified 526
      total bacterial operational taxonomic units (OTUs, 97% similarity), primarily
      from Firmicutes (92.6%) and Proteobacteria (6.9%), via 16S rRNA gene amplicon
      sequencing. Resident ocular communities of healthy female finches were
      characterized by greater evenness and phylogenetic diversity compared to healthy
      male finches. Regardless of sex, ocular microbiome community structure
      significantly shifted 11 days after experimental inoculation with M.
      gallisepticum. A suite of OTUs, including taxa from the genera Methylobacterium,
      Acinetobacter and Mycoplasma, appear to drive these changes, indicating that the
      whole finch ocular microbiome responds to infection. Further study is needed to
      quantify changes in absolute abundance of resident taxa and to elucidate
      potential functional roles of the resident ocular microbiome in mediating
      individual responses to this common songbird bacterial pathogen.

PMID- 27871126
TI  - Metagenomic analysis reveals unusually high incidence of proteorhodopsin genes in
      the ultraoligotrophic Eastern Mediterranean Sea.
AB  - Sunlight can be directly harvested by photoheterotrophic bacteria to create a pH
      gradient across the membrane, which can then be utilized to produce ATP. Despite
      the potential importance of this trophic strategy, when and where such organisms
      are found in the seas and oceans is poorly described. Here, we describe the
      abundance and taxonomy of bacteria with different trophic strategies
      (heterotrophs, phototrophs and photoheterotrophs) in contrasting water masses of
      the ultra-oligotrophic eastern Mediterranean Sea. These water bodies, an
      anticyclonic eddy and a high-chlorophyll patch resulting from transport of
      nutrient-rich coastal waters into offshore oligotrophic waters, each supported
      different microbial populations in surface waters. Based on infrared microscopy
      and metagenomics, aerobic anoxygenic photoheterotrophic (AAP) bacteria
      represented up to 10.4% of the microbial community. In contrast, the
      proteorhodopsin (PR) gene was found in 78.6%-118.8% of the bacterial genome
      equivalents, the highest abundance reported to date. These results suggest that
      PR-mediated photoheterotrophy may be especially important in oligotrophic,
      potentially phosphate-limited conditions.

PMID- 27871128
TI  - Hand-assisted laparoscopic left hepatectomy: how I do it.
AB  - Laparoscopic liver resection has been adopted slowly due to concerns for bleeding
      and oncologic outcomes. Currently, over 9,500 laparoscopic liver resections have
      been performed and reported worldwide. Numerous studies have shown the safety and
      oncologic equivalence of laparoscopic liver resection when compared to open
      resection. Pure laparoscopic and hand-assisted laparoscopic liver resection are
      the two most commonly used techniques for minimally invasive liver resection
      surgery. Advantages of the hand-port include tactile feedback, facilitation of
      liver mobilization, and ease of ability to control bleeding. We present a case
      report with video of a hand-assisted laparoscopic left liver resection for a
      hepatocellular carcinoma in a non-cirrhotic patient.

PMID- 27871129
TI  - A comment on the discussion and application of statistical methods in Mandrup et
      al. Low-dose effects of bisphenol A on mammary gland development in rats
      (Andrology 4: 673-683, 2016).

PMID- 27871127
TI  - Effect of maternal position on fetal behavioural state and heart rate variability
      in healthy late gestation pregnancy.
AB  - KEY POINTS: Fetal behavioural state in healthy late gestation pregnancy is
      affected by maternal position. Fetal state 1F is more likely to occur in maternal
      supine or right lateral positions. Fetal state 4F is less likely to occur when
      the woman lies supine or semi-recumbent. Fetal state change is more likely when
      the woman is supine or semi-recumbent. Fetal heart rate variability is affected
      by maternal position with variability reduced in supine and semi-recumbent
      positions. ABSTRACT: Fetal behavioural states (FBS) are measures of fetal
      wellbeing. In acute hypoxaemia, the human fetus adapts to a lower oxygen
      consuming state with changes in the cardiotocograph and reduced fetal activity.
      Recent studies of late gestation stillbirth described the importance of sleep
      position in the risk of intrauterine death. We designed this study to assess the
      effects of different maternal positions on FBS in healthy late gestation
      pregnancies under controlled conditions. Twenty-nine healthy women had continuous
      fetal ECG recordings under standardized conditions in four randomly allocated
      positions, left lateral, right lateral, supine and semi-recumbent. Two blinded
      observers, assigned fetal states in 5 min blocks. Measures of fetal heart rate
      variability were calculated from ECG beat to beat data. Compared to state 2F,
      state 4F was less likely to occur when women were semi-recumbent [odds ratio (OR)
      = 0.11, 95% confidence interval (95% CI) 0.02, 0.55], and supine (OR = 0.27, 95%
      CI 0.07, 1.10). State 1F was more likely on the right (OR = 2.36, 95% CI 1.11,
      5.04) or supine (OR = 4.99, 95% CI 2.41, 10.43) compared to the left. State
      change was more likely when the mother was semi-recumbent (OR = 2.17, 95% CI
      1.19, 3.95) or supine (OR = 2.67, 95% CI 1.46, 4.85). There was a significant
      association of maternal position to mean fetal heart rate. The measures of heart
      rate variability (SDNN and RMSSD) were reduced in both semi-recumbent and supine
      positions. In healthy late gestation pregnancy, maternal position affects FBS and
      heart rate variability. These effects are likely fetal adaptations to positions
      which may produce a mild hypoxic stress.

PMID- 27871130
TI  - PAAR-Rhs proteins harbor various C-terminal toxins to diversify the antibacterial
      pathways of type VI secretion systems.
AB  - The type VI secretion system (T6SS) of bacteria plays a key role in competing for
      specific niches by the contact-dependent killing of competitors. Recently, Rhs
      proteins with polymorphic C-terminal toxin-domains that inhibit or kill
      neighboring cells were identified. In this report, we identified a novel Rhs with
      an MPTase4 (Metallopeptidase-4) domain (designated as Rhs-CT1) that showed an
      antibacterial effect via T6SS in Escherichia coli. We managed to develop a
      specific strategy by matching the diagnostic domain-architecture of Rhs-CT1 (Rhs
      with an N-terminal PAAR-motif and a C-terminal toxin domain) for effector
      retrieval and discovered a series of Rhs-CTs in E. coli. Indeed, the screened Rhs
      CT3 with a REase-3 (Restriction endonuclease-3) domain also mediated
      interbacterial antagonism. Further analysis revealed that vgrGO1 and eagR/DUF1795
      (upstream of rhs-ct) were required for the delivery of Rhs-CTs, suggesting eagR
      as a potential T6SS chaperone. In addition to chaperoned Rhs-CTs, neighborless
      Rhs-CTs could be classified into a distinct family (Rhs-Nb) sharing close
      evolutionary relationship with T6SS2-Rhs (encoded in the T6SS2 cluster of E.
      coli). Notably, the Rhs-Nb-CT5 was confirmed bioinformatically and experimentally
      to mediate interbacterial antagonism via Hcp2B-VgrG2 module. In a further
      retrieval analysis, we discovered various toxin/immunity pairs in extensive
      bacterial species that could be systematically classified into eight referential
      clans, suggesting that Rhs-CTs greatly diversify the antibacterial pathways of
      T6SS.

PMID- 27871131
TI  - Metabolomic changes in response to toxic arsenite.

PMID- 27871132
TI  - Aspergillus penicillioides differentiation and cell division at 0.585 water
      activity.
AB  - Water availability acts as the most stringent constraint for life on Earth. Thus,
      understanding the water relations of microbial extremophiles is imperative to our
      ability to increase agricultural productivity (e.g., by enhancing the processing
      and turnover of dead organic matter in soils of arid regions), reduce human
      exposure to mycotoxins in buildings and our food-supply chain, prevent the
      spoilage of foods/animal feeds, books, museum specimens and artworks and better
      control microbiology of industrial fermentations. Only a small number of
      microbial systems can retain activity at <0.710 water activity (ISME J 2015 9:
      1333-1351). It has long-been considered that the most resilient of these is
      Xeromyces bisporus, which inhabits sugar-rich substrates (Appl Environ Microbiol
      1968 16: 1853-1858). The current study focused on germination of Aspergillus
      penicillioides, a xerophile which is also able to grow under low humidity and
      saline conditions. Investigations of germination differed from those reported
      earlier: firstly, aerially borne conidia were harvested, and then used for
      inoculations, in their dry condition; secondly, cultures were incubated at 24
      degrees C, i.e. below optimum germination temperature, to minimize the
      possibility of water loss from the substrate; thirdly, cultures remained sealed
      throughout the 73-day study period (microscopic examination was carried out
      directly 48 through the Petri plate lid); fourthly, the germination parameters
      determined were: rates and extent of conidial swelling, production of
      differentiated germination-structures and septate germlings, and subsequent
      development of mycelium and/or sporulation; fifthly, assessments were carried out
      over a range of water-activity values and time points to obtain a complete
      profile of the germination process. Conidia swelled, formed differentiated
      germination-structures and then produced septate germlings at a water-activity of
      just 0.585 (=58.5% relative humidity), outside the currently understood
      thermodynamic window for life. Furthermore, analyses of these data suggest a
      theoretical water-activity minimum of 0.565 for germination of A. penicilliodes.
      In relation to astrobiology, these findings have an application in understanding
      the limits to life in extraterrestrial environments. In light of current plans
      for exploration missions to Mars and other places, and the need to safeguard
      martian scientific sites and potential resources (including water) for future
      human habitation, a knowledge-based and effective policy for planetary protection
      is essential. As it is, Mars-bound spacecraft may frequently be contaminated with
      aspergilli (including A. penicillioides) and other organisms which, when
      transported to other planetary bodies, pose a contamination risk. In crafting
      countermeasures to offset this, it is important to know as precisely as possible
      the capabilities of these potential interplanetary visitors.

PMID- 27871133
TI  - Civilian cerebral gunshot wounds: a South African experience.
AB  - BACKGROUND: Cerebral gunshot wounds represent one of the most lethal forms of
      traumatic brain injury, but there is a paucity of literature on the topic,
      especially from the developing world. We reviewed our experience and describe the
      spectrum and outcome of civilian cerebral gunshot wounds in a major metropolitan
      trauma centre in South Africa. METHODS: This was a retrospective study of all
      patients with isolated cerebral gunshot wounds managed by the Pietermaritzburg
      Metropolitan Trauma Service over a 5-year period from 2010 to 2014. RESULTS: One
      hundred and two patients were included, 92% (94/102) were male and the mean age
      was 29 years. Fifty-four per cent (55/102) of all patients were from urban areas.
      The mean time from injury to arrival was 6 h (standard deviation: 5) for urban
      patients and 15 h (standard deviation: 5.2) for rural patients (P < 0.001).
      Ninety-four per cent (94/102) of all injuries were related to interpersonal
      violence and involved low velocity firearms. Twenty per cent of all patients
      (20/102) had a Glasgow Coma Scale 3-8, 20% (20/102) 9-12 and 61% (61/102) 12-15.
      All 102 patients underwent computed tomography scans. Thirty per cent (31/102)
      required neurosurgical interventions. The overall mortality rate was 22%
      (22/102). There was a significant difference in mortality between urban and rural
      patients (9% versus 36%, P < 0.001). CONCLUSIONS: Cerebral gunshot wounds are
      associated with significant mortality and protracted delay to definitive care is
      common in our setting. Those who survive the delayed transfer to definitive care
      generally do well and have reasonably good clinical outcomes.

PMID- 27871134
TI  - When green algae turn red.

PMID- 27871135
TI  - Fire modifies the phylogenetic structure of soil bacterial co-occurrence
      networks.
AB  - Fire alters ecosystems by changing the composition and community structure of
      soil microbes. The phylogenetic structure of a community provides clues about its
      main assembling mechanisms. While environmental filtering tends to reduce the
      community phylogenetic diversity by selecting for functionally (and hence
      phylogenetically) similar species, processes like competitive exclusion by
      limiting similarity tend to increase it by preventing the coexistence of
      functionally (and phylogenetically) similar species. We used co-occurrence
      networks to detect co-presence (bacteria that co-occur) or exclusion (bacteria
      that do not co-occur) links indicative of the ecological interactions structuring
      the community. We propose that inspecting the phylogenetic structure of co
      presence or exclusion links allows to detect the main processes simultaneously
      assembling the community. We monitored a soil bacterial community after an
      experimental fire and found that fire altered its composition, richness and
      phylogenetic diversity. Both co-presence and exclusion links were more
      phylogenetically related than expected by chance. We interpret such a
      phylogenetic clustering in co-presence links as a result of environmental
      filtering, while that in exclusion links reflects competitive exclusion by
      limiting similarity. This suggests that environmental filtering and limiting
      similarity operate simultaneously to assemble soil bacterial communities,
      widening the traditional view that only environmental filtering structures
      bacterial communities.

PMID- 27871136
TI  - Contribution of different dispersal sources to the metabolic response of lake
      bacterioplankton following a salinity change.
AB  - Dispersal can modify how bacterial community composition (BCC) changes in
      response to environmental perturbations, yet knowledge about the functional
      consequences of dispersal is limited. Here we hypothesized that changes in
      bacterial community production in response to a salinity disturbance depend on
      the possibility to recruit cells from different dispersal sources. To investigate
      this, we conducted an in situ mesocosm experiment where bacterial communities of
      an oligotrophic lake were exposed to different salinities (0, 18, 36 psu) for 2
      weeks and subjected to dispersal of cells originating from sediments, air
      (mesocosms open to air deposition), both or none. BCC was determined using 454
      pyrosequencing of the 16S rRNA gene and bacterial production was measured by 3 H
      leucine uptake. Bacterial production differed significantly among salinity
      treatments and dispersal treatments, being highest at high salinity. These
      changes were associated with changes in BCC and it was found that the identity of
      the main functional contributors differed at different salinities. Our results
      further showed that after a salinity perturbation, the response of bacterial
      communities depended on the recruitment of taxa, including marine representatives
      (e.g., Alphaproteobacteria Loktanella, Erythrobacter and the Gammaproteobacterium
      Rheiheimera) from dispersal sources, in which atmospheric deposition appeared to
      play a major role.

PMID- 27871137
TI  - New insights in the early extracellular events in hydrocarbon and lipid
      biodegradation.

PMID- 27871139
TI  - Glycerol stress in Saccharomyces cerevisiae: Cellular responses and evolved
      adaptations.
AB  - Glycerol synthesis is key to central metabolism and stress biology in
      Saccharomyces cerevisiae, yet the cellular adjustments needed to respond and
      adapt to glycerol stress are little understood. Here, we determined impacts of
      acute and chronic exposures to glycerol stress in S. cerevisiae. Glycerol stress
      can result from an increase of glycerol concentration in the medium due to the S.
      cerevisiae fermenting activity or other metabolic activities. Acute glycerol
      stress led to a 50% decline in growth rate and altered transcription of more than
      40% of genes. The increased genetic diversity in S. cerevisiae population, which
      had evolved in the standard nutrient medium for hundreds of generations, led to
      an increase in growth rate and altered transcriptome when such population was
      transferred to stressful media containing a high concentration of glycerol; 0.41
      M (0.990 water activity). Evolution of S. cerevisiae populations during a 10-day
      period in the glycerol-containing medium led to transcriptome changes and
      readjustments to improve control of glycerol flux across the membrane, regulation
      of cell cycle, and more robust stress response; and a remarkable increase of
      growth rate under glycerol stress. Most of the observed regulatory changes arose
      in duplicated genes. These findings elucidate the physiological mechanisms, which
      underlie glycerol-stress response, and longer-term adaptations, in S. cerevisiae;
      they also have implications for enigmatic aspects of the ecology of this
      otherwise well-characterized yeast.

PMID- 27871140
TI  - Metabolic response of Agrobacterium tumefaciens 5A to arsenite.
AB  - Wide-spread abundance in soil and water, coupled with high toxicity have put
      arsenic at the top of the list of environmental contaminants. Early studies
      demonstrated that both concentration and the valence state of inorganic arsenic
      (arsenite, As(III) vs. arsenate As(V)) can be modulated by microbes. Using
      genetics, transcriptomic and proteomic techniques, microbe-arsenic
      detoxification, respiratory As(V) reduction and As(III) oxidation have since been
      examined. The effect of arsenic exposure on whole-cell intracellular microbial
      metabolism, however, has not been extensively studied. We combined LC-MS and 1 H
      NMR to quantify metabolic changes in Agrobacterium tumefaciens (strain 5A) upon
      exposure to sub-lethal concentrations of As(III). Metabolomics analysis reveals
      global differences in metabolite concentrations between control and As(III)
      exposure groups, with significant perturbations to intermediates shuttling into
      and cycling within the TCA cycle. These data are most consistent with the
      disruption of two key TCA cycle enzymes, pyruvate dehydrogenase and alpha
      ketoglutarate dehydrogenase. Glycolysis also appeared altered following As(III)
      stress, with carbon accumulating as complex saccharides. These observations
      suggest that an important consequence of As(III) contamination in nature will be
      to alter microbial carbon metabolism at the microbial community level and thus
      has the potential to foundationally impact all biogeochemical cycles in the
      environment.

PMID- 27871138
TI  - High genetic diversity of Vibrio cholerae in the European lake Neusiedler See is
      associated with intensive recombination in the reed habitat and the long-distance
      transfer of strains.
AB  - Coastal marine Vibrio cholerae populations usually exhibit high genetic
      diversity. To assess the genetic diversity of abundant V. cholerae non-O1/non
      O139 populations in the Central European lake Neusiedler See, we performed a
      phylogenetic analysis based on recA, toxR, gyrB and pyrH loci sequenced for 472
      strains. The strains were isolated from three ecologically different habitats in
      a lake that is a hot-spot of migrating birds and an important bathing water. We
      also analyzed 76 environmental and human V. cholerae non-O1/non-O139 isolates
      from Austria and other European countries and added sequences of seven genome
      sequenced strains. Phylogenetic analysis showed that the lake supports a unique
      endemic diversity of V. cholerae that is particularly rich in the reed stand.
      Phylogenetic trees revealed that many V. cholerae isolates from European
      countries were genetically related to the strains present in the lake belonging
      to statistically supported monophyletic clades. We hypothesize that the observed
      phenomena can be explained by the high degree of genetic recombination that is
      particularly intensive in the reed stand, acting along with the long distance
      transfer of strains most probably via birds and/or humans. Thus, the Neusiedler
      See may serve as a bioreactor for the appearance of new strains with new
      (pathogenic) properties.

PMID- 27871141
TI  - Root isoflavonoids and hairy root transformation influence key bacterial taxa in
      the soybean rhizosphere.
AB  - Rhizodeposits play a key role in shaping rhizosphere microbial communities. In
      soybean, isoflavonoids are a key rhizodeposit component that aid in plant defense
      and enable symbiotic associations with rhizobia. However, it is uncertain if and
      how they influence rhizosphere microbial communities. Isoflavonoid biosynthesis
      was silenced via RNA interference of isoflavone synthase in soybean hairy root
      composite plants. Rhizosphere soil fractions tightly associated with roots were
      isolated, and PCR amplicons from 16S rRNA gene variable regions V1-V3 and V3-V5
      from these fractions were sequenced using 454. The resulting data was resolved
      using MOTHUR and vegan to identify bacterial taxa and evaluate changes in
      rhizosphere bacterial communities. The soybean rhizosphere was enriched in
      Proteobacteria and Bacteroidetes, and had relatively lower levels of
      Actinobacteria and Acidobacteria compared with bulk soil. Isoflavonoids had a
      small effect on bacterial community structure, and in particular on the abundance
      of Xanthomonads and Comamonads. The effect of hairy root transformation on
      rhizosphere bacterial communities was largely similar to untransformed plant
      roots with approximately 74% of the bacterial families displaying similar
      colonization underscoring the suitability of this technique to evaluate the
      influence of plant roots on rhizosphere bacterial communities. However, hairy
      root transformation had notable influence on Sphingomonads and Acidobacteria.

PMID- 27871142
TI  - Identification of two mutations that cause defects in the ligninolytic system
      through an efficient forward genetics in the white-rot agaricomycete Pleurotus
      ostreatus.
AB  - White-rot fungi play an important role in the global carbon cycle because they
      are the species that almost exclusively biodegrade wood lignin in nature. Lignin
      peroxidases (LiPs), manganese peroxidases (MnPs) and versatile peroxidases (VPs)
      are considered key players in the ligninolytic system. Apart from LiPs, MnPs and
      VPs, however, only few other factors involved in the ligninolytic system have
      been investigated using molecular genetics, implying the existence of
      unidentified elements. By combining classical genetic techniques with next
      generation sequencing technology, they successfully showed an efficient forward
      genetics approach to identify mutations causing defects in the ligninolytic
      system of the white-rot fungus Pleurotus ostreatus. In this study, they
      identified two genes - chd1 and wtr1 - mutations in which cause an almost
      complete loss of Mn2+ -dependent peroxidase activity. The chd1 gene encodes a
      putative chromatin modifier, and wtr1 encodes an agaricomycete-specific protein
      with a putative DNA-binding domain. The chd1-1 mutation and targeted disruption
      of wtr1 hamper the ability of P. ostreatus to biodegrade wood lignin. Examination
      of the effects of the aforementioned mutation and disruption on the expression of
      certain MnP/VP genes suggests that a complex mechanism underlies the ligninolytic
      system in P. ostreatus.

PMID- 27871144
TI  - The unexpected versatility of the cellulosome.

PMID- 27871143
TI  - Bringing microbial diversity into focus: high-resolution analysis of iron mats
      from the Lo'ihi Seamount.
AB  - Thirty kilometers south of the island of Hawai'i lies the Lo'ihi Seamount, an
      active submarine volcano that hosts a network of low-temperature hydrothermal
      vents enriched in ferrous iron that supports extensive microbial mats. These
      mats, which can be a half a meter deep, are composed of ferric iron bound to
      organic polymers - the metabolic byproduct of iron-oxidizing Zetaproteobacteria.
      Though the role of Zetaproteobacteria in mat formation is well established, we
      have a limited understanding of how differences in diversity are related to mat
      morphology. We used Minimum Entropy Decomposition and ZetaOtu classification to
      demonstrate cryptic diversity between closely related Zetaproteobacteria while
      showing habitat and geographic specificity. Veiled mats, common structures at
      Lo'ihi, exhibit distinct community composition and contain diversity not detected
      in other mat types, including specific Zetaproteobacteria and an unclassified
      Gammaproteobacteria. Our analyses also indicate that diversity can change
      dramatically across small spatial transects from points of active venting, yet we
      found comparatively few differences between major sampling sites. This study
      provides a better picture of the microbiome responsible for iron mat production
      at Lo'ihi and has broad implications for our understanding of these globally
      distributed communities.

PMID- 27871145
TI  - Meta-omic analyses of Baltic Sea cyanobacteria: diversity, community structure
      and salt acclimation.
AB  - Cyanobacteria are important phytoplankton in the Baltic Sea, an estuarine-like
      environment with pronounced north to south gradients in salinity and nutrient
      concentrations. Here, we present a metagenomic and -transcriptomic survey, with
      subsequent analyses targeting the genetic identity, phylogenetic diversity, and
      spatial distribution of Baltic Sea cyanobacteria. The cyanobacterial community
      constituted close to 12% of the microbial population sampled during a pre-bloom
      period (June-July 2009). The community was dominated by unicellular
      picocyanobacteria, specifically a few highly abundant taxa (Synechococcus and
      Cyanobium) with a long tail of low abundance representatives, and local peaks of
      bloom-forming heterocystous taxa. Cyanobacteria in the Baltic Sea differed
      genetically from those in adjacent limnic and marine waters as well as from
      cultivated and sequenced picocyanobacterial strains. Diversity peaked at brackish
      salinities 3.5-16 psu, with low N:P ratios. A shift in community composition from
      brackish to marine strains was accompanied by a change in the repertoire and
      expression of genes involved in salt acclimation. Overall, the pre-bloom
      cyanobacterial population was more genetically diverse, widespread and abundant
      than previously documented, with unicellular picocyanobacteria being the most
      abundant clade along the entire Baltic Sea salinity gradient.

PMID- 27871146
TI  - Abundant and rare picoeukaryotic sub-communities present contrasting patterns in
      the epipelagic waters of marginal seas in the northwestern Pacific Ocean.
AB  - In this work, they compared patterns of abundant and rare picoeukaryotic sub
      communities in the epipelagic waters (surface and 40-75 m depth subsurface
      layers) of the East and South China Seas across seasons via 454 pyrosequencing of
      the V4 region of 18S rDNA. They also examined the relative effects of
      environmental filtering, dispersal limitations and seasonality on community
      assembly. Their results indicated that (i) in the surface layer, abundant taxa
      are primarily influenced by dispersal limitations and rare taxa are primarily
      influenced by environmental filtering, whereas (ii) in the subsurface layer, both
      abundant and rare sub-communities are only weakly influenced by environmental
      filtering but are strongly influenced by dispersal limitations. Moreover, (iii)
      abundant taxa exhibit stronger temporal variability than rare taxa. They also
      found that abundant and rare sub-communities display similar spatial richness
      patterns that are negatively correlated with latitude and chlorophyll a and
      positively correlated with temperature. In summary, environmental filtering and
      dispersal limitations have different effects on abundant and rare picoeukaryotic
      sub-communities in different layers. Thus, depth appears as an essential variable
      that governs the structuring patterns of picoeukaryotic communities in the oceans
      and should be thoroughly considered to develop a more comprehensive understanding
      of oceanic microbial assemblages.

PMID- 27871147
TI  - Shared and host-specific microbiome diversity and functioning of grapevine and
      accompanying weed plants.
AB  - Weeds and crop plants select their microbiota from the same pool of soil
      microorganisms, however, the ecology of weed microbiomes is poorly understood. We
      analysed the microbiomes associated with roots and rhizospheres of grapevine and
      four weed species (Lamium amplexicaule L., Veronica arvensis L., Lepidium draba
      L. and Stellaria media L.) growing in proximity in the same vineyard using 16S
      rRNA gene sequencing. We also isolated and characterized 500 rhizobacteria and
      root endophytes from L. draba and grapevine. Microbiome data analysis revealed
      that all plants hosted significantly different microbiomes in the rhizosphere as
      well as in root compartment, however, differences were more pronounced in the
      root compartment. The shared microbiome of grapevine and the four weed species
      contained 145 OTUs (54.2%) in the rhizosphere, but only nine OTUs (13.2%) in the
      root compartment. Seven OTUs (12.3%) were shared in all plants and compartments.
      Approximately 56% of the major OTUs (>1%) showed more than 98% identity to
      bacteria isolated in this study. Moreover, weed-associated bacteria generally
      showed a higher species richness in the rhizosphere, whereas the root-associated
      bacteria were more diverse in the perennial plants grapevine and L. draba.
      Overall, weed isolates showed more plant growth-promoting characteristics
      compared with grapevine isolates.

PMID- 27871148
TI  - Composition and diversity of mucosa-associated microbiota along the entire length
      of the pig gastrointestinal tract; dietary influences.
AB  - Mucosa-associated microbial populations of the gastrointestinal tract are in
      intimate contact with the outer mucus layer. This proximity offers these
      populations a higher potential, than lumenal microbiota, in exerting effects on
      the host. Functional characteristics of the microbiota and influences of host
      physiology shape the composition and activity of the mucosa-associated bacterial
      community. We have shown previously that inclusion of an artificial sweetener,
      SUCRAM, included in the diet of weaning piglets modulates the composition of
      lumenal-residing gut microbiota and reduces weaning-related gastrointestinal
      disorders. In this study, using Illumina sequencing we characterised the mucosa
      associated microbiota along the length of the intestine of piglets, and
      determined the effect of SUCRAM supplementation on mucosa-associated populations.
      There were clear distinctions in the composition of mucosa-associated microbiota,
      between small and large intestine, concordant with differences in regional oxygen
      distribution and nutrient provision by the host. There were significant
      differences in the composition of mucosa-associated compared with lumenal
      microbiota in pig caecum. Dietary supplementation with SUCRAM affected mucosa
      associated bacterial community structure along the length of the intestinal
      tract. Most notably, there was a substantial reduction in predominant
      Campylobacter populations proposing that SUCRAM supplementation of swine diet has
      potential for reducing meat contamination and promoting food safety.

PMID- 27871149
TI  - PSTha5a23, a candidate effector from the obligate biotrophic pathogen Puccinia
      striiformis f. sp. tritici, is involved in plant defense suppression and rust
      pathogenicity.
AB  - During the infection of host plants, pathogens can deliver virulence-associated
      'effector' proteins to promote plant susceptibility. However, little is known
      about effector function in the obligate biotrophic pathogen Puccinia striiformis
      f. sp. tritici (Pst) that is an important fungal pathogen in wheat production
      worldwide. Here, they report their findings on an in planta highly induced
      candidate effector from Pst, PSTha5a23. The PSTha5a23 gene is unique to Pst and
      shows a low level of intra-species polymorphism. It has a functional N-terminal
      signal peptide and is translocated to the host cytoplasm after infection.
      Overexpression of PSTha5a23 in Nicotiana benthamiana was found to suppress the
      programmed cell death triggered by BAX, PAMP-INF1 and two resistance-related
      mitogen-activated protein kinases (MKK1 and NPK1). Overexpression of PSTha5a23 in
      wheat also suppressed pattern-triggered immunity (PTI)-associated callose
      deposition. In addition, silencing of PSTha5a23 did not change Pst virulence
      phenotypes; however, overexpression of PSTha5a23 significantly enhanced Pst
      virulence in wheat. These results indicate that the Pst candidate effector
      PSTha5a23 plays an important role in plant defense suppression and rust
      pathogenicity, and also highlight the utility of gene overexpression in plants as
      a tool for studying effectors from obligate biotrophic pathogens.

PMID- 27871150
TI  - Integrated proteomics and metabolomics suggests symbiotic metabolism and
      multimodal regulation in a fungal-endobacterial system.
AB  - Many plant-associated fungi host endosymbiotic endobacteria with reduced genomes.
      While endobacteria play important roles in these tri-partite plant-fungal
      endobacterial systems, the active physiology of fungal endobacteria has not been
      characterized extensively by systems biology approaches. Here, we use integrated
      proteomics and metabolomics to characterize the relationship between the
      endobacterium Mycoavidus sp. and the root-associated fungus Mortierella elongata.
      In nitrogen-poor media, M. elongata had decreased growth but hosted a large and
      growing endobacterial population. The active endobacterium likely extracted
      malate from the fungal host as the primary carbon substrate for energy production
      and biosynthesis of phospho-sugars, nucleobases, peptidoglycan and some amino
      acids. The endobacterium obtained nitrogen by importing a variety of nitrogen
      containing compounds. Further, nitrogen limitation significantly perturbed the
      carbon and nitrogen flows in the fungal metabolic network. M. elongata regulated
      many pathways by concordant changes on enzyme abundances, post-translational
      modifications, reactant concentrations and allosteric effectors. Such multimodal
      regulations may be a general mechanism for metabolic modulation.

PMID- 27871151
TI  - Therapeutic Potential of Human Mesenchymal Stem Cells for Treating Ischemic Limb
      Diseases.
AB  - Ischemic limb diseases are induced by different obstructions of peripheral
      arteries. These obstructions result in insufficient nutrient and oxygen supplies
      to the extremities, thereby leading to severe tissue damage that is in turn
      related to severe morbidities and mortalities. Mesenchymal stem cells (MSCs) have
      been isolated from various sources. These cells are multipotent with respect to
      differentiation and are also characterized by migration, immune suppression, and
      secretion of paracrine factors. Mesenchymal stem cells have been proposed to have
      therapeutic potential for the treatment of ischemic limb diseases. In preclinical
      experiments, injection of single MSCs has been shown to increase angiogenesis and
      blood flow in ischemic hindlimb animal models; several molecular mechanisms of
      angiogenesis have also been elucidated. Furthermore, modified strategies have
      been developed for enhancing angiogenesis and the efficacy of MSCs. These
      strategies have demonstrated significant effects in pre-clinical studies. In
      clinical trials, MSCs have shown significant effects in the treatment of ischemic
      limb diseases. In this review, we focus on the therapeutic properties of human
      MSCs and the modified methods for enhancing angiogenesis in pre-clinical
      experiments. We also discuss the clinical applications of MSCs for treating limb
      ischemia.

PMID- 27871152
TI  - Human Adipose-derived Mesenchymal Stem Cells Attenuate Early Stage of Bleomycin
      Induced Pulmonary Fibrosis: Comparison with Pirfenidone.
AB  - Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive,
      irreversible, invariably fatal fibrotic lung disease with no lasting option for
      therapy. Mesenchymal stem cells (MSCs) could be a promising modality for the
      treatment of IPF. Aim of the study was to investigate improvement in
      survivability and anti-fibrotic efficacy of human adipose-derived mesenchymal
      stem cells (AD-MSCs) in comparison with pirfenidone in the bleomycin-induced
      pulmonary fibrosis model. Methods: Human AD-MSCs were administered intravenously
      on day 3, 6 and 9 after an intra-tracheal challenge with bleomycin, whereas,
      pirfenidone was given orally in drinking water at the rate of 100 mg/kg body
      weight three times a day daily from day 3 onward. AD-MSCs were labelled with PKH
      67 before administration to detect engraftment. Disease severity and improvement
      was assessed and compared between sham control and vehicle control groups using
      Kaplan-Meier survival analysis, biochemical and molecular analysis,
      histopathology and high resolution computed tomography (HRCT) parameters at the
      end of study. Results: Results demonstrated that AD-MSCs significantly increase
      survivability; reduce organ weight and collagen deposition better than
      pirfenidone group. Histological analyses and HRCT of the lung revealed that AD
      MSCs afforded protection against bleomycin induced fibrosis and protect
      architecture of the lung. Gene expression analysis revealed that AD-MSCs potently
      suppressed pro-fibrotic genes induced by bleomycin. More importantly, AD-MSCs
      were found to inhibit pro-inflammatory related transcripts. Conclusions: Our
      results provided direct evidence that AD-MSC-mediated immunomodulation and anti
      fibrotic effect in the lungs resulted in marked protection in pulmonary fibrosis,
      but at an early stage of disease.

PMID- 27871153
TI  - In vivo Evaluation of Human Embryonic Stem Cells Isolated by 57-C11 Monoclonal
      Antibody.
AB  - Background: The normal cells derived from human embryonic stem cells (hESCs) are
      regarded as substitutes for damaged or dysfunctional adult cells. However,
      tumorigenicity of hESCs remains a major challenge in clinical application of hESC
      derived cell transplantation. Previously, we generated monoclonal antibody (MAb)
      57-C11 specific to the surface molecule on undifferentiated hESCs. The aim of
      this study is to prove whether 57-C11-positive hESCs are pluripotent and
      tumorigenic in immunodeficient mice. Methods: Undifferentiated hESCs were mixed
      with retinoic acid (RA)-differentiated hESCs at different ratios prior to 57-C11
      mediated separation. To isolate 57-C11-positive hESCs from the mixture,
      biotinylated 57-C11 and streptavidin-coated magnetic beads were added to the
      mixture. Unbound 57-C11-negative hESCs were first isolated after applying magnet
      to the cell mixture, and 57-C11-bound hESCs were then released from the magnetic
      beads. In order to measure the efficiency of separation, 57-C11-positive or 
      negative hESCs were counted after isolation. To evaluate the efficiency of
      teratoma formation in vivo, 57-C11-positive or negative cells were further
      injected into left and right, respectively, testes of nonobese diabetic/severe
      combined immunodeficiency (NOD/SCID) mice. Results: Approximately 77~100% of
      undifferentiated hESCs were isolated after applying 57-C11-coated magnetic beads
      to the mixed cell populations. Importantly, teratomas were not observed in
      NOD/SCID mice after the injection of isolated 57-C11-negative hESCs, whereas
      teratomas were observed with 57-C11-positive hESCs. Conclusion: 57-C11-positive
      hESCs are pluripotent and tumorigenic. The combination of 57-C11 and magnetic
      beads will be useful to eliminate remaining undifferentiated hESCs for the safe
      cell transplantation.

PMID- 27871154
TI  - Neuroprotection of Dexmedetomidine against Cerebral Ischemia-Reperfusion Injury
      in Rats: Involved in Inhibition of NF-kappaB and Inflammation Response.
AB  - Dexmedetomidine is an alpha2-adrenergic receptor agonist that exhibits a
      protective effect on ischemia-reperfusion injury of the heart, kidney, and other
      organs. In the present study, we examined the neuroprotective action and
      potential mechanisms of dexmedetomidine against ischemia-reperfusion induced
      cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced
      in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic
      insult, animals then received intravenous dexmedetomidine of 1 ug/kg load dose,
      followed by 0.05 ug/kg/min infusion for 2 h. After 24 h of reperfusion,
      neurological function, brain edema, and the morphology of the hippocampal CA1
      region were evaluated. The levels and mRNA expressions of interleukin-1beta,
      interleukin-6 and tumor nevrosis factor-alpha as well as the protein expression
      of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-kappaBp65,
      inhibitor of kappaBalpha and phosphorylated of kappaBalpha in hippocampus were
      assessed. We found that dexmedetomidine reduced focal cerebral ischemia
      reperfusion injury in rats by inhibiting the expression and release of
      inflammatory cytokines and mediators. Inhibition of the nuclear factor-kappaB
      pathway may be a mechanism underlying the neuroprotective action of
      dexmedetomidine against focal cerebral I/R injury.

PMID- 27871156
TI  - Kahweol from Coffee Induces Apoptosis by Upregulating Activating Transcription
      Factor 3 in Human Colorectal Cancer Cells.
AB  - Kahweol as a coffee-specific diterpene has been reported to induce apoptosis in
      human cancer cells. Although some molecular targets for kahweol-mediated
      apoptosis have been elucidated, the further mechanism for apoptotic effect of
      kahweol is not 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 kahweol stimulates ATF3
      expression and apoptosis in human colorectal cancer cells. Kahweol increased
      apoptosis in human colorectal cancer cells. It also increased ATF3 expression
      through the transcriptional activity. The responsible cis-element for ATF3
      transcriptional activation by kahweol was CREB located between -147 to -85 of
      ATF3 promoter. ATF3 overexpression increased kahweol-mediated cleaved PARP, while
      ATF3 knockdown attenuated the cleavage of PARP by kahweol. Inhibition of ERK1/2
      and GSK3beta blocked kahweol-mediated ATF3 expression. The results suggest that
      kahweol induces apoptosis through ATF3-mediated pathway in human colorectal
      cancer cells.

PMID- 27871155
TI  - Protective Role of Fucoidan in Cerebral Ischemia-Reperfusion Injury through
      Inhibition of MAPK Signaling Pathway.
AB  - Fucoidan has been reported to exhibit various beneficial activities ranging from
      to antivirus and anticancer properties. However, little information is available
      about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our
      study aimed to explore the effects of fucoidan on cerebral IRI, as well as the
      underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four
      groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160
      mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally
      injected from 7 days before the rats were induced to cerebral IRI model with
      middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion,
      neurological deficits and the total infarct volume were determined. The levels of
      inflammation-associated cytokines (interleukin (IL)-1beta, IL-6, myeloperoxidase
      (MPO), and tumor necrosis factor (TNF)-alpha), oxidative stress-related proteins
      (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were
      measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of
      apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen
      activated protein kinase (MAPK) pathway (phosphorylation-extracellular
      signalregulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were
      measured. Results showed that administration of fucoidan significantly reduced
      the neurological deficits and infarct volume compared to the IRI+S group in a
      dose-dependent manner. Also, fucoidan statistically decreased the levels of
      inflammation-associated cytokines, and oxidative stress-related proteins,
      inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a
      protective role in cerebral IRI might be by inhibition of MAPK pathway.

PMID- 27871157
TI  - Synthetic Cannabinoid-Induced Immunosuppression Augments Cerebellar Dysfunction
      in Tetanus-Toxin Treated Mice.
AB  - Synthetic cannabinoids are one of most abused new psychoactive substances. The
      recreational use of abused drug has aroused serious concerns about the
      consequences of these drugs on infection. However, the effects of synthetic
      cannabinoid on resistance to tetanus toxin are not fully understood yet. In the
      present study, we aimed to determine if the administration of synthetic
      cannabinoids increase the susceptibility to tetanus toxin-induced motor
      behavioral deficit and functional changes in cerebellar neurons in mice.
      Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which
      against tetanus toxin. JWH-210 administration decreased expression levels of T
      cell activators including cluster of differentiation (CD) 3epsilon, CD3gamma,
      CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor
      impairment and decrement of vesicle-associated membrane proteins 2 levels in the
      cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar
      glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as
      evidenced by increased glutamate concentration levels in the cerebellum. These
      results suggest that JWH-210 may increase the vulnerability to tetanus toxin via
      the regulation of immune function.

PMID- 27871159
TI  - [Acute Kidney Injury in Cirrhotic Patients with Portal Hypertension].
AB  - Acute kidney injury (AKI) is one of the most common manifestations encountered in
      clinical practice. It is associated with high morbidity and mortality in
      cirrhotic pre- and post-transplantation patients. Hepatorenal syndrome (HRS), a
      special form of AKI in cirrhotic patients, was recognized as a consequence of
      renal vasoconstriction from systemic/renal hemodynamic alterations developed in
      advanced cirrhosis with portal hypertension. Recently, multiple factors-such as
      infection/inflammation, underlying glomerulonephritis, bile cast, or increased
      abdominal pressure-have been considered to contribute to renal dysfunction in
      cirrhotic patients, which were presumed to induce HRS. Moreover, in addition to
      changing the definition of AKI in the nephrologic guidelines, the new AKI
      definition for early diagnosis and intervention based on characteristics of liver
      cirrhosis has been proposed in an international meeting. This article provides a
      comprehensive and recent review of AKI definition, laying out the topics in
      accordance with the pathophysiologic mechanisms and therapeutic interventions of
      AKI in cirrhotic patients with portal hypertension.

PMID- 27871158
TI  - Platelet Shape Changes and Cytoskeleton Dynamics as Novel Therapeutic Targets for
      Anti-Thrombotic Drugs.
AB  - Platelets play an essential role in hemostasis through aggregation and adhesion
      to vascular injury sites but their unnecessary activation can often lead to
      thrombotic diseases. Upon exposure to physical or biochemical stimuli, remarkable
      platelet shape changes precede aggregation or adhesion. Platelets shape changes
      facilitate the formation and adhesion of platelet aggregates, but are readily
      reversible in contrast to the irrevocable characteristics of aggregation and
      adhesion. In this dynamic phenomenon, complex molecular signaling pathways and a
      host of diverse cytoskeleton proteins are involved. Platelet shape change is
      easily primed by diverse pro-thrombotic xenobiotics and stimuli, and its
      inhibition can modulate thrombosis, which can ultimately contribute to the
      development or prevention of thrombotic diseases. In this review, we discussed
      the current knowledge on the mechanisms of platelet shape change and also
      pathological implications and therapeutic opportunities for regulating the
      related cytoskeleton dynamics.

PMID- 27871160
TI  - Clinical Outcome of Doublet and Triplet Neoadjuvant Chemotherapy for Locally
      Advanced Gastric Cancer.
AB  - Background/Aims: In gastric cancer, the rate of recurrence and metastasis
      following radical resection is high, necessitating improvement in survival and
      cure rates. Neoadjuvant chemotherapy (NAC) has potential benefits for locally
      advanced gastric cancer; however, the surgical benefits and effects on survival
      are unclear. This study evaluates the effectiveness of NAC in locally advanced
      gastric cancer and compares clinical outcomes of doublet and triplet regimens.
      Methods: We reviewed patient medical records of 383 patients who underwent NAC
      (n=41) or surgery only (n=342) for treatment of locally advanced gastric cancer.
      The baseline characteristics and clinical outcomes were compared between the
      groups. Chemotherapy patients were classified according to regimen, doublet
      (n=28) and triplet (n=13), and NAC-related clinical response, safety, and
      toxicity were analyzed. Results: The baseline characteristics did not differ
      significantly between groups. After NAC, the tumor downstage rate was 51.2%
      (21/41); however, overall survival (p=0.205) and disease-free survival (p=0.415)
      were not significantly different between the groups. On subgroup analysis, no
      significant differences in drug toxicity (p=0.604) or clinical response (p=0.374)
      were found between outcomes of doublet and triplet chemotherapy regimens.
      Conclusions: In patients with locally advanced gastric cancer, NAC showed
      tolerable drug toxicity and increased tumor downstage, but NAC failed to increase
      the survival rate, which may be caused by a high D2-lymphadenectomy rate.
      Therefore, NAC was found to be a therapeutic option for select gastric cancer
      patients.

PMID- 27871161
TI  - Helicobacter pylori Eradication Modulates Aberrant CpG Island Hypermethylation in
      Gastric Carcinogenesis.
AB  - Background/Aims: Helicobacter pylori infection induces aberrant DNA methylation
      in gastric mucosa. We evaluated the long-term effect of H. pylori eradication on
      promotor CpG island hypermethylation in gastric carcinogenesis. Methods: H.
      pylori-positive patients with gastric adenoma or early gastric cancer who
      underwent endoscopic resection were enrolled. According to H. pylori eradication
      after endoscopic resection, the participants were randomly assigned to H. pylori
      eradication or non-eradication group. H. pylori-negative gastric mucosa from
      normal participants provided the normal control. CpG island hypermethylation of
      tumor-related genes (p16, CDH1, and RUNX-3) was evaluated by quantitative
      MethyLight assay in non-tumorous gastric mucosa. The gene methylation rate and
      median values of hypermethylation were compared after one year by H. pylori
      status. Results: In H. pylori-positive patients, hypermethylation of p16 was
      found in 80.6%, of CDH1 in 80.6%, and of RUNX-3 in 48.4%. This is significantly
      higher than normal control (p16, 10%; CDH1, 44%; RUNX-3, 16%) (p<0.05). In the H.
      pylori eradication group, methylation rates of p16 and CDH1 decreased in 58.1%
      and 61.3% of the patients, and the median values of hypermethylation were
      significantly lower at one year compared with the non-eradication group. However,
      RUNX-3 hypermethylation did not differ significantly at one year after H. pylori
      eradication. The non-eradication group hypermethylation did not change after one
      year. Conclusions: H. pylori infection was associated with promotor
      hypermethylation of genes in gastric carcinogenesis, and H. pylori eradication
      might reverse p16 and CDH1 hypermethylation.

PMID- 27871163
TI  - A Case of Endoscopically Complete Remission of Esophageal Neuroendocrine Tumors
      by Concurrent Chemoradiation Therapy.
AB  - Neuroendocrine tumors (NETs) of the esophagus are extremely rare, aggressive and
      have a poor prognosis. Combined therapy using chemotherapy, radiotherapy and/or
      surgery appear effective. Here, we present a patient with a complaint of
      dysphagia who was diagnosed with this rare tumor. Upper gastrointestinal
      endoscope of a 46-year-old female revealed a localized ulcerative lesion in the
      middle esophagus. Histologic exam of biopsy specimens indicated a neuroendocrine
      carcinoma. The tumor cells were arranged in microtubular structures, with small
      and round cells containing scanty cytoplasm. They were positive for synaptophysin
      and chromogranin A on immunohistochemical staining. A computed tomography scan
      showed an esophageal tumor with enlarged superior mediastinal lymph nodes and
      about 1.2 cm sized liver metastasis, similar to findings in PET-CT scanning. The
      patient was prescribed chemotherapy consisting of etoposide and cisplatin, which
      led to regression of disease on follow-up imaging study. She continues under
      clinical observation. We seek to increase awareness of this exceedingly rare but
      hazardous disease by sharing our unexpected finding.

PMID- 27871164
TI  - [A Case of Biliary Obstruction Caused by Liver Cyst].
AB  - Most cystic lesions of the liver are found incidentally in imaging studies
      because they are not symptomatic, and generally do not require treatment. Rarely,
      however, symptomatic hepatic cysts may develop complications and require
      treatment. Here, we describe a case of a 77-year-old woman who developed biliary
      obstruction with abdominal pain due to compression of the bile duct by a simple
      hepatic cyst. We confirmed the diagnosis based on symptoms and imaging studies.
      The patient'ssymptoms improved after simple cyst ablation by sclerotherapy.

PMID- 27871165
TI  - Acute Pancreatitis Complicated with Diabetic Ketoacidosis in a Young Adult
      without Hypertriglyceridemia: A Case Report.
AB  - Systemic complications related to acute pancreatitis include acute respiratory
      distress syndrome, multiple organ dysfunction syndrome, disseminated
      intravascular coagulation, hypocalcemia, hyperglycemia, and insulin dependent
      diabetes or diabetic ketoacidosis. In practice, the development of diabetic
      ketoacidosis induced by acute pancreatitis is rare and generally associated with
      hypertriglyceridemia. However, herein we report a case of a 34-year-old female
      without hypertriglyceridemia, who was diagnosed with acute pancreatitis
      complicated with diabetic ketoacidosis. The patient was admitted with complaints
      of febrile sensation, back pain, and abdominal pain around the epigastric area.
      Levels of serum amylase and lipase were elevated to 663 U/L and 3,232 U/L.
      Contrast-enhanced abdominal CT showed pancreatic swelling, peri-pancreatic fat
      infiltration and fluid collection. The patient was initially diagnosed with
      simple acute pancreatitis. Though the symptoms were rapidly relieved after
      initiation of treatment, severe hyperglycemia (575 mg/dL), severe metabolic
      acidosis (pH 6.9), and ketonuria developed at four days after hospitalization.
      However, serum triglyceride levels remained within the normal range (134 mg/dL).
      Finally, the patient was diagnosed with acute pancreatitis complicated with
      diabetic ketoacidosis unrelated to hypertriglyceridemia. She recovered through
      insulin and fluid therapy, and receives insulin therapy at the outpatient clinic.

PMID- 27871166
TI  - Traumatic Neuroma at the Inferior Mesenteric Artery Stump after Rectal Cancer
      Surgery: A Case Report and Literature Review.
AB  - Traumatic neuroma results from regeneration attempts of the proximal end of an
      injured or severed nerve, resulting in a non-neoplastic nodular lesion. The lower
      extremity after amputation is the most common site, followed by the head and
      neck. Traumatic neuromas occurring in the abdomen, however, are rare. In the
      abdominal region, traumatic neuromas occur in the cystic duct stump and the
      common bile ducts as well as around the celiac trunk. This study reports a case
      of a 59-year-old man who presented with a traumatic neuroma arising at the stump
      of the inferior mesenteric artery after rectal cancer surgery. Traumatic neuromas
      at the stump of the inferior mesenteric artery have not been previously reported.
      The lesion exhibited atypical imaging features, including a well-enhanced nodule,
      a significant interval growth in size and a mild increase in 18F-fluo
      rodeoxyglucose uptake, resembling lymph node metastasis. This case report will
      help physicians understand the sites of occurrence and imaging features of
      traumatic neuromas in the abdomen.

PMID- 27871162
TI  - Eradication Rate by Duration of Third-line Rescue Therapy with Levofloxacin after
      Helicobacter pylori Treatment Failure in Clinical Practice.
AB  - Background/Aims: This study evaluated the eradication rate of levofloxacin
      containing rescue therapy by treatment duration in patients in whom previous
      first- and second-line treatment failed. Methods: Fifty-five patients with
      persistent Helicobacter pylori infection after first-line therapy and second-line
      therapy were studied in a single referral academic center. We compared the
      eradication rates by the treatment duration of third-line therapy. Results: Of 55
      patients, 12 (21.8%) received rescue therapy for seven days, 24 (43.6%) received
      rescue therapy for 10 days, and 19 (34.5%) received rescue therapy for 14 days.
      The eradication rates of therapy with levofloxacin were 65.5% in the 55 enrolled
      patients and 73.5% in the 49 patients who underwent follow-up testing. In cases
      where follow-up testing was performed, the eradication rate of 7-day therapy was
      58.3%, of 10-day 68.2%, and of 14-day therapy 93.3%. Eradication rate of 14-day
      therapy was higher than 7-day (p=0.06) and 10-day (p=0.108), but chance could not
      be ruled out in the difference among groups. Conclusions: This study showed
      somewhat increasing of H. pylori eradication rate by extending the duration of
      levofloxacin-containing rescue therapy to 14 days.

PMID- 27871167
TI  - [Corrigendum: Current Status of Translational Research on Functional Dyspepsia].

PMID- 27871168
TI  - Long-term prognosis of end-stage renal disease patients with normal myocardial
      perfusion as determined by single photon emission computed tomography.
AB  - BACKGROUND/AIMS: Normal myocardial perfusion is closely associated with very low
      rates of cardiac events and better long-term outcomes; however, little is known
      about its prognostic value in patients with end-stage renal disease (ESRD).
      METHODS: A total of 286 incident patients underwent baseline cardiac evaluations
      using echocardiography and stress-rest single-photon emission computed
      tomography. Perfusion scans for 177 patients (61.9%) who had a summed stress
      score (SSS) < 4 were normal. RESULTS: During the 4-year follow-up period, 79
      cardiac events occurred. Patients with a SSS < 4 had significantly lower annual
      rates of cardiac events than did those with a SSS >= 4 (6.4% vs. 13.2%; hazard
      ratio, 0.54; 95% confidence interval, 0.31 to 0.94). Among patients with a SSS <
      4, however, cardiac event rates significantly differed according to the presence
      of comorbid conditions such as old age, diabetes, history of coronary artery
      disease, and elevated C-reactive protein levels. In addition, the presence of
      left ventricular (LV) systolic dysfunction and LV hypertrophy at the start of
      hemodialysis strongly influenced future cardiac events. CONCLUSIONS: In patients
      with ESRD, normal perfusion scans usually indicate a significantly low risk of
      adverse cardiac events. However, even in patients with normal perfusion scans,
      the cardiovascular prognosis is largely dependent on baseline inflammation levels
      and comorbidities.

PMID- 27871169
TI  - Structural and Biochemical Studies Reveal a Putative FtsZ Recognition Site on the
      Z-ring Stabilizer ZapD.
AB  - FtsZ, a tubulin homologue, is an essential protein of the Z-ring assembly in
      bacterial cell division. It consists of two domains, the N-terminal and C
      terminal core domains, and has a conserved C-terminal tail region. Lateral
      interactions between FtsZ protofilaments and several Z-ring associated proteins
      (Zaps) are necessary for modulating Z-ring formation. ZapD, one of the positive
      regulators of Z-ring assembly, directly binds to the C-terminal tail of FtsZ and
      promotes stable Z-ring formation during cytokinesis. To gain structural and
      functional insights into how ZapD interacts with the C-terminal tail of FtsZ, we
      solved two crystal structures of ZapD proteins from Salmonella typhimurium
      (StZapD) and Escherichia coli (EcZapD) at a 2.6 and 3.1 A resolution,
      respectively. Several conserved residues are clustered on the concave sides of
      the StZapD and EcZapD dimers, the suggested FtsZ binding site. Modeled structures
      of EcZapD-EcFtsZ and subsequent binding studies using bio-layer interferometry
      also identified the EcFtsZ binding site on EcZapD. The structural insights and
      the results of bio-layer interferometry assays suggest that the two FtsZ binding
      sites of ZapD dimer might be responsible for the binding of ZapD dimer to two
      protofilaments to hold them together.

PMID- 27871170
TI  - Allele-Specific Phenotype Suggests a Possible Stimulatory Activity of RCAN-1 on
      Calcineurin in Caenorhabditis elegans.
AB  - Regulator of calcineurin 1 (RCAN1) binds to calcineurin through the PxIxIT motif,
      which is evolutionarily conserved. SP repeat phosphorylation in RCAN1 is required
      for its complete function. The specific interaction between RCAN1 and calcineurin
      is critical for calcium/calmodulin-dependent regulation of calcineurin
      serine/threonine phosphatase activity. In this study, we investigated two
      available deletion rcan-1 mutants in Caenorhabditis elegans, which proceed
      differently for transcription and translation. We found that rcan-1 may be
      required for calcineurin activity and possess calcineurin-independent function in
      body growth and egg-laying behavior. In the genetic background of enhanced
      calcineurin activity, the rcan-1 mutant expressing a truncated RCAN-1 which
      retains the calcineurin-binding PxIxIT motif but misses SP repeats stimulated
      growth, while rcan-1 lack mutant resulted in hyperactive egg-laying suppression.
      These data suggest rcan-1 has unknown functions independent of calcineurin, and
      may be a stimulatory calcineurin regulator under certain circumstances.

PMID- 27871171
TI  - Cell-SELEX Based Identification of an RNA Aptamer for Escherichia coli and Its
      Use in Various Detection Formats.
AB  - Escherichia coli are important indicator organisms, used routinely for the
      monitoring of water and food safety. For quick, sensitive and real-time detection
      of E. coli we developed a 2'F modified RNA aptamer Ec3, by Cell-SELEX. The 31
      nucleotide truncated Ec3 demonstrated improved binding and low nano-molar
      affinity to E. coli. The aptamer developed by us out-performs the commercial
      antibody and aptamer used for E. coli detection. Ec3(31) aptamer based E. coli
      detection was done using three different detection formats and the assay
      sensitivities were determined. Conventional Ec3(31)-biotin-streptavidin magnetic
      separation could detect E. coli with a limit of detection of 1.3 * 106 CFU/ml.
      Although, optical analytic technique, biolayer interferometry, did not improve
      the sensitivity of detection for whole cells, a very significant improvement in
      the detection was seen with the E. coli cell lysate (5 * 104 CFU/ml). Finally we
      developed Electrochemical Impedance Spectroscopy (EIS) gap capacitance biosensor
      that has detection limits of 2 * 104 CFU/mL of E. coli cells, without any
      labeling and signal amplification techniques. We believe that our developed
      method can step towards more complex and real sample application.

PMID- 27871173
TI  - STAT3 Potentiates SIAH-1 Mediated Proteasomal Degradation of beta-Catenin in
      Human Embryonic Kidney Cells.
AB  - The beta-catenin functions as an adhesion molecule and a component of the Wnt
      signaling pathway. In the absence of the Wnt ligand, beta-catenin is constantly
      phosphorylated, which designates it for degradation by the APC complex. This
      process is one of the key regulatory mechanisms of beta-catenin. The level of
      beta-catenin is also controlled by the E3 ubiquitin protein ligase SIAH-1 via a
      phosphorylation-independent degradation pathway. Similar to beta-catenin, STAT3
      is responsible for various cellular processes, such as survival, proliferation,
      and differentiation. However, little is known about how these molecules work
      together to regulate diverse cellular processes. In this study, we investigated
      the regulatory relationship between STAT3 and beta-catenin in HEK293T cells. To
      our knowledge, this is the first study to report that beta-catenin-TCF-4
      transcriptional activity was suppressed by phosphorylated STAT3; furthermore,
      STAT3 inactivation abolished this effect and elevated activated beta-catenin
      levels. STAT3 also showed a strong interaction with SIAH-1, a regulator of active
      beta-catenin via degradation, which stabilized SIAH-1 and increased its
      interaction with beta-catenin. These results suggest that activated STAT3
      regulates active beta-catenin protein levels via stabilization of SIAH-1 and the
      subsequent ubiquitin-dependent proteasomal degradation of beta-catenin in HEK293T
      cells.

PMID- 27871172
TI  - LIN-23, an E3 Ubiquitin Ligase Component, Is Required for the Repression of CDC
      25.2 Activity during Intestinal Development in Caenorhabditis elegans.
AB  - Caenorhabditis elegans (C. elegans) utilizes two different cell-cycle modes,
      binucleations during the L1 larval stage and endoreduplications at four larval
      moltings, for its postembryonic intestinal development. Previous genetic studies
      indicated that CDC-25.2 is specifically required for binucleations at the L1
      larval stage and is repressed before endoreduplications. Furthermore, LIN-23, the
      C. elegans beta-TrCP ortholog, appears to function as a repressor of CDC-25.2 to
      prevent excess intestinal divisions. We previously reported that intestinal
      hyperplasia in lin-23(e1883) mutants was effectively suppressed by the RNAi
      depletion of cdc-25.2. Nevertheless, LIN-23 targeting CDC-25.2 for ubiquitination
      as a component of E3 ubiquitin ligase has not yet been tested. In this study, LIN
      23 is shown to be the major E3 ubiquitin ligase component, recognizing CDC-25.2
      to repress their activities for proper transition of cell-cycle modes during the
      C. elegans postembryonic intestinal development. In addition, for the first time
      that LIN-23 physically interacts with both CDC-25.1 and CDC-25.2 and facilitates
      ubiquitination for timely regulation of their activities during the intestinal
      development.

PMID- 27871174
TI  - Viral Inhibition of PRR-Mediated Innate Immune Response: Learning from KSHV
      Evasion Strategies.
AB  - The innate immune system has evolved to detect and destroy invading pathogens
      before they can establish systemic infection. To successfully eradicate
      pathogens, including viruses, host innate immunity is activated through diverse
      pattern recognition receptors (PRRs) which detect conserved viral signatures and
      trigger the production of type I interferon (IFN) and pro-inflammatory cytokines
      to mediate viral clearance. Viral persistence requires that viruses co-opt
      cellular pathways and activities for their benefit. In particular, due to the
      potent antiviral activities of IFN and cytokines, viruses have developed various
      strategies to meticulously modulate intracellular innate immune sensing
      mechanisms to facilitate efficient viral replication and persistence. In this
      review, we highlight recent advances in the study of viral immune evasion
      strategies with a specific focus on how Kaposi's sarcoma-associated herpesvirus
      (KSHV) effectively targets host PRR signaling pathways.

PMID- 27871176
TI  - In Vivo Angiogenic Capacity of Stem Cells from Human Exfoliated Deciduous Teeth
      with Human Umbilical Vein Endothelial Cells.
AB  - Dental pulp is a highly vascularized tissue requiring adequate blood supply for
      successful regeneration. In this study, we investigated the functional role of
      stem cells from human exfoliated deciduous teeth (SHEDs) as a perivascular source
      for in vivo formation of vessel-like structures. Primarily isolated SHEDs showed
      mesenchymal stem cell (MSC)-like characteristics including the expression of
      surface antigens and in vitro osteogenic and adipogenic differentiation
      potentials. Moreover, SHEDs were positive for NG2, alpha-smooth muscle actin
      (SMA), platelet-derived growth factor receptor beta (PDGFRbeta), and CD146 as
      pericyte markers. To prove feasibility of SHEDs as perivascular source, SHEDs
      were transplanted into immunodeficient mouse using Matrigel with or without human
      umbilical vein endothelial cells (HUVECs). Transplantation of SHEDs alone or
      HUVECs alone resulted in no formation of vessel-like structures with enough red
      blood cells. However, when SHEDs and HUVECs were transplanted together, extensive
      vessel-like structures were formed. The presence of murine erythrocytes within
      lumens suggested the formation of anastomoses between newly formed vessel-like
      structures in Matrigel plug and the host circulatory system. To understand
      underlying mechanisms of in vivo angiogenesis, the expression of angiogenic
      cytokine and chemokine, their receptors, and MMPs was compared between SHEDs and
      HUVECs. SHEDs showed higher expression of VEGF, SDF-1alpha, and PDGFRbeta than
      HUVECs. On the contrary, HUVECs showed higher expression of VEGF receptors,
      CXCR4, and PDGF-BB than SHEDs. This differential expression pattern suggested
      reciprocal interactions between SHEDs and HUVECs and their involvement during in
      vivo angiogenesis. In conclusion, SHEDs could be a feasible source of
      perivascular cells for in vivo angiogenesis.

PMID- 27871175
TI  - Epigenetic Changes in Neurodegenerative Diseases.
AB  - Afflicted neurons in various neurodegenerative diseases generally display diverse
      and complex pathological features before catastrophic occurrence of massive
      neuronal loss at the late stages of the diseases. This complex nature of neuronal
      pathophysiology inevitably implicates systemwide changes in basic cellular
      activities such as transcriptional controls and signal cascades, and so on, as a
      cause. Recently, as one of these systemwide cellular changes associated with
      neurodegenerative diseases, epigenetic changes caused by protein toxicity have
      begun to be highlighted. Notably, recent advances in related techniques including
      next-generation sequencing (NGS) and mass spectrometry enable us to monitor
      changes in the post-translational modifications (PTMs) of histone proteins and to
      link these changes in histone PTMs to the specific transcriptional changes.
      Indeed, epigenetic alterations and consequent changes in neuronal transcriptome
      are now begun to be extensively studied in neurodegenerative diseases including
      Alzheimer's disease (AD). In this review, we will discuss details of our current
      understandings on epigenetic changes associated with two representative
      neurodegenerative diseases [AD and polyglutamine (polyQ) diseases] and further
      discuss possible future development of pharmaceutical treatment of the diseases
      through modulating these epigenetic changes.

PMID- 27871178
TI  - Use of polyethylene glycol in functional constipation and fecal impaction.
AB  - OBJECTIVE: The objective of this study was to evaluate in an analytical and
      descriptive manner the evidence published so far on the use of polyethylene
      glycol (PEG), with or without electrolytes, in the management of functional
      constipation and the treatment of fecal impaction. METHODOLOGY: Search on
      MEDLINE, EMBASE and Cochrane databases until May 2016 of all publications
      adjusted to the following terms: constipation AND/OR fecal impaction AND (PEG OR
      polyethylene glycol OR macrogol OR movicol OR idralax OR miralax OR transipeg OR
      forlax OR golytely OR isocolan OR mulytely) NOT colonoscopy. Critical reading of
      selected articles (English or Spanish), sorting their description according to
      group age (adult/pediatric age) and within those, in accordance with study
      features (efficacy evaluation versus placebo, doses query, safety, comparison
      with other laxatives, observational studies and monographic review articles of
      polyethylene glycol or meta-analysis). RESULTS: Fifty-eight publications have
      been chosen for descriptive analysis; of them, 41 are clinical trials, eight are
      observational studies and nine are systematic reviews or meta-analysis. Twelve
      clinical trials evaluate PEG efficacy versus placebo, eight versus lactulose, six
      are dose studies, five compare polyethylene glycol with and without electrolytes,
      two compare its efficacy with respect to milk of magnesia, and the rest of the
      trials evaluate polyethylene glycol with enemas (two), psyllium (one), tegaserod
      (one), prucalopride (one), paraffin oil (one), fiber combinations (one) and
      Descurainia sophia (one). CONCLUSIONS: Polyethylene glycol with or without
      electrolytes is more efficacious than placebo for the treatment of functional
      constipation, either in adults or in pediatric patients, with great safety and
      tolerability. These preparations constitute the most efficacious osmotic
      laxatives (more than lactulose) and are the first-line treatment for functional
      constipation in the short and long-term. They are as efficacious as enemas in
      fecal impaction, avoid the need for hospital admission and are well tolerated by
      patients (mainly when administered without electrolytes).

PMID- 27871179
TI  - Validating competencies for an undergraduate training program in rural medicine
      using the Delphi technique.
AB  - INTRODUCTION: Worldwide,<b> </b>half the population lives in rural or remote
      areas; however, less than 25% of doctors work in such regions. Despite the
      continental dimensions of Brazil and its enormous cultural diversity, only some
      medical schools in this country offer students the opportunity to acquire work
      experience focused on medicine in rural or remote areas. The objective of the
      present study was to develop a framework of competencies for a longitudinal
      medical training program in rural medicine as an integrated part of medical
      training in Brazil. METHODS: Two rounds of a modified version of the Delphi
      technique were conducted. Initially, a structured questionnaire was elaborated,
      based on a literature review. This questionnaire was submitted to the opinion of
      20 panelists affiliated with the Rural Medicine Working Party of the Brazilian
      Society of Family and Community Medicine. The panelists were asked to evaluate
      the relevance of the competencies using a five-point Likert-type scale. In this
      study, the consensus criterion for a competency to be included in the framework
      was it being deemed 'very important' or 'indispensable' by a simple majority of
      the participants, while the criterion for excluding a competency was that a
      simple majority of the panel members considered that it 'should not be included'
      or was 'of little importance'. When a consensus was not reached regarding a given
      competency, it was submitted to a second round to enable the panelists to re
      evaluate the now dichotomized questions. RESULTS: Compliance in responding to the
      questionnaire was better among the panelists predominantly involved in teaching
      activities (85%; <i>n</i>=12) compared to those working principally in patient
      care (45%; <i>n</i>=8). The questionnaire consisted of 26 core competencies and
      165 secondary competencies. After evaluation by the specialists, all the 26 core
      competencies were classified as relevant, with none being excluded and only eight
      secondary competencies failing to achieve a consensus. No new competencies were
      suggested. Of the competencies that failed to reach a consensus in the first
      round, seven were excluded from the framework in the second round, with most of
      these being associated with hospital procedures. CONCLUSIONS: A framework of
      competencies for a program in rural medicine was developed and validated. It
      consists of 26 core competencies and 158 secondary competencies that should be
      useful when constructing competency-based curricula in rural medicine for medical
      education in Brazil.

PMID- 27871177
TI  - Glucose and Insulin Stimulate Lipogenesis in Porcine Adipocytes: Dissimilar and
      Identical Regulation Pathway for Key Transcription Factors.
AB  - Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other
      transcription factors in response to glucose and insulin. The isolated porcine
      preadipocytes were differentiated into mature adipocytes to investigate the roles
      and interrelation of these transcription factors in the context of glucose- and
      insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose
      induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was
      unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed
      adipocytes irrespective of glucose concentration, suggesting ChREBP mediate
      glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when
      SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by
      ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced
      lipogenesis. LXRalpha activation promoted lipogenesis and lipogenic genes
      expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes,
      LXRalpha activation facilitated lipogenesis and SREBP-1c expression, but had no
      effect on ChREBP expression. Therefore, LXRalpha might mediate lipogenesis via
      SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c
      activation blocked simultaneously, glucose and insulin were still able to
      stimulated lipogenesis and lipogenic genes expression, and LXRalpha activation
      enhanced these effects, suggesting LXRalpha mediated directly glucose- and
      insulin-induced lipogenesis. In summary, glucose and insulin stimulated
      lipogenesis through both dissimilar and identical regulation pathway in porcine
      adipocytes.

PMID- 27871181
TI  - Iron stains on paper. Can electrophoretic removal become an effective alternative
      to chemical cleaning?
AB  - Research in restoration and conservation is directed vs. more sustainable working
      materials, methods and technologies. Electrophoretic removal, from porous
      material, of undesired stains due to charged species is theoretically an
      interesting alternative to chemical cleaning methods, but the lack of specific
      and comprehensive research work leads to controversial opinions about the
      efficiency and the needed harmfulness for the treated objects. In this work
      paper, samples with artificial rust stains were subjected to electrophoretic
      cleaning treatments in mineral water as electrolyte. Treatments were carried out
      either in a bath by complete sample immersion between the distanced electrodes or
      by sample wetting and sandwiching between the electrodes. Evaluation of cleaning
      efficiency and treatment effects was based on colour change measurements (image
      analysis of scanned paper samples before and after the treatment and by
      colorimetric data via spectrophotometric measurements), investigation of
      morphological changes by SEM observations and folding endurance measurements.

PMID- 27871180
TI  - Prescription opioid prescribing, use/misuse, harms and treatment among Aboriginal
      people in Canada: a narrative review of available data and indicators.
AB  - INTRODUCTION: Prescription opioid (PO) misuse and related harms are high in
      Canada, and a major public health challenge. In Canada, 1.4 million individuals
      (4.3% of the total population) self-identify as Aboriginal, among whom substance
      use and related harms are elevated. While there are reports of PO use and
      associated problems among Aboriginal groups, no comprehensive data review
      currently exists. METHODS: A review of available data sources (ie journal
      publications, public reports and 'grey' literature) was conducted following
      principles of a scoping review. Information and data were identified, extracted,
      and organized into major indicator categories: <i>PO prescribing/dispensing</i>,
      <i>use/abuse</i>, <i>morbidity/mortality harms and treatment</i>, and narratively
      reported. RESULTS: Data suggest that PO dispensing, use and misuse levels among
      Aboriginal populations are high and/or rising in select settings when compared to
      the general Canadian population. High levels of PO-related dependence and
      pregnancy harms exist (mainly in Northern Ontario); there is some indication of
      elevated opioid mortality among Aboriginals. Vast discrepancies in availability
      and access to interventions exist; some recent pilot studies suggest improved
      care. CONCLUSIONS: Data regarding PO use and harms among Aboriginal people are
      limited, even though elevated problem levels are indicated; improved monitoring,
      and more effective yet culturally and contextually appropriate interventions for
      this acute problem are needed.

PMID- 27871182
TI  - Chemometric analysis of minerals and trace elements in Sicilian wines from two
      different grape cultivars.
AB  - Chemometric analysis are used for food authenticity evaluation, correlating
      botanical and geographical origins with food chemical composition. This research
      was carried out in order to prove that it is possible linked red wines to Nero
      d'Avola and Syrah cultivars of Vitis vinifera according to their mineral content,
      while the values of the physical and chemical parameters do not affect relevantly
      this discrimination. The levels of mineral elements were determined by ICP-OES
      and ICP-MS. Samples from cv Nero d'Avola had the highest content of Zn, Cr, Ni,
      As and Cd, whereas the highest mineral concentration in cv Syrah samples was
      represented by K, Mg, Cu, and Sb. The research highlights that it is possible
      linked red wines to Nero d'Avola and Syrah cultivars of V. vinifera according to
      their mineral contents, adding knowledge to the determination studies of the wine
      botanical origin.

PMID- 27871184
TI  - In vitro evaluation of prebiotic properties derived from rice bran obtained by
      debranning technology.
AB  - The prebiotic ability of several rice bran fractions obtained by debranning (RBD)
      using human microbiota was studied in anaerobic batch cultures with agitation and
      pH-controlled. Fraction C (3.8-5% w/w pearling) from RBD increased the number of
      bifidobacteria and lactobacteria compared with the positive control, raftilose
      P95. RBD fermentation induced changes in the short-chain fatty acid (SCFA)
      profile. In addition, Fraction C revealed the highest growth of positive
      lactobacteria than commercial control. The present work illustrates the prebiotic
      capacity of RBD to modulate human microbiota and highlights that fraction C could
      be an economical source for use in human food as well as an interesting
      alternative to valorise a by-product of cereal industry.

PMID- 27871183
TI  - HIV patient and provider feedback on a telehealth collaborative care for
      depression intervention.
AB  - In the HIV Translating Initiatives for Depression into Effective Solutions
      project, we conducted a randomized controlled effectiveness and implementation
      trial comparing depression collaborative care with enhanced usual care in
      Veterans Health Administration HIV clinics in the US. An offsite HIV depression
      care team including a psychiatrist, a depression care manager (DCM), and a
      clinical pharmacist provided collaborative care using a stepped-care model of
      treatment and made recommendations to providers through the electronic health
      record system. The DCM delivered care management to HIV patients through phone
      calls, performing routine assessments and providing counseling in self-management
      and problem-solving. The DCM documented all calls in each patient's electronic
      medical record. In this paper we present results from interviews conducted with
      patients and clinical staff in a multi-stage formative evaluation (FE). We
      conducted semi-structured FE interviews with 26 HIV patients and 30 clinical
      staff at the three participating sites during and after the trial period to
      gather their experiences and perspectives concerning the intervention components.
      Interviews were transcribed verbatim and analyzed using rapid content analysis
      techniques. Patients reported high satisfaction with the depression care manager
      (DCM) phone calls. Both HIV and mental health providers reported that the DCM's
      chart notes in the electronic health record were very helpful, and most felt that
      a dedicated DCM for HIV patients is ideal to meet patient needs. Sites
      encountered barriers to achieving and maintaining universal depression screening,
      but had greater success when such screening was incorporated into routine intake
      processes. FE results demonstrated that depression care management via telehealth
      from an offsite team is acceptable and helpful to both HIV patients and their
      providers. Given that a centralized offsite depression care team can deliver
      effective, cost-effective, cost-saving services for multiple HIV clinics in
      different locations with high patient and provider satisfaction, broad
      implementation should be considered.

PMID- 27871185
TI  - Interventions that increase the intention to seek voluntary HIV testing in young
      people: a review.
AB  - Young people 15-24 years old represent 39% of new HIV infections globally.
      However, they are the least likely age demographic to seek HIV testing and the
      most likely to be unaware of their HIV status. The purpose of this systematic
      literature review was to identify interventions that increase either rates of HIV
      testing or intentions to seek HIV testing in young people 10-24 years old. In
      total, 1601 manuscripts were systematically examined and five manuscripts were
      included in the final review. Two common themes identified in the interventions
      were education and test delivery methods. Educational programs were found to be
      effective when delivered in classroom or entertainment-based formats. Health
      providers offering testing and home testing increased the rate of testing.
      Additional research is needed on programs aimed at young people not enrolled in
      schools, interventions that measure testing rates, and educating healthcare
      providers about offering HIV tests to young people.

PMID- 27871186
TI  - Does a TV Public Service Advertisement Campaign for Suicide Prevention Really
      Work?
AB  - BACKGROUND: One of the critical measures in suicide prevention is promoting
      public awareness of crisis hotline numbers so that individuals can more readily
      seek help in a time of crisis. Although public service advertisements (PSA) may
      be effective in raising the rates of both awareness and use of a suicide hotline,
      few investigations have been performed regarding their effectiveness in South
      Korea, where the suicide rate is the highest among OECD countries. AIMS: The goal
      of this study was to evaluate the effectiveness of a television PSA campaign.
      METHOD: We analyzed a database of crisis phone calls compiled by the Korean
      Ministry of Health and Welfare to track changes in call volume to a crisis
      hotline that was promoted in a TV campaign. We compared daily call counts for
      three periods of equal length: before, during, and after the campaign. RESULTS:
      The number of crisis calls during the campaign was about 1.6 times greater than
      the number before or after the campaign. Relative to the number of suicide
      related calls in the previous year, the number of calls during the campaign
      period surged, displaying a noticeable increase. CONCLUSION: The findings
      confirmed that this campaign had a positive impact on call volume to the suicide
      hotline.

PMID- 27871187
TI  - Hepatoprotective triterpenoids and lignans from the stems of Schisandra
      pubescens.
AB  - One new triterpenoid (1) and 13 known compounds (2-14) were isolated from
      Schisandra pubescens stems. The structure of the new compound was established on
      the basis of 1D/2D NMR and HRESIMS spectroscopic analyses. The isolated compounds
      were evaluated for their hepatoprotective activities against D-GalN-induced cell
      injury in QSG7701 cells. Compounds 1, 13 and 14 at 10 MUM showed hepatoprotective
      activities, with survival rates of 60.5, 50.4 and 48.9%, respectively.

PMID- 27871188
TI  - What can 35 years and over 700,000 measurements tell us about noise exposure in
      the mining industry?
AB  - OBJECTIVE: To analyse over 700,000 cross-sectional measurements from the Mine
      Safety and Health Administration (MHSA) and develop statistical models to predict
      noise exposure for a worker. DESIGN: Descriptive statistics were used to
      summarise the data. Two linear regression models were used to predict noise
      exposure based on MSHA-permissible exposure limit (PEL) and action level (AL),
      respectively. Twofold cross validation was used to compare the exposure estimates
      from the models to actual measurement. The mean difference and t-statistic was
      calculated for each job title to determine whether the model predictions were
      significantly different from the actual data. STUDY SAMPLE: Measurements were
      acquired from MSHA through a Freedom of Information Act request. RESULTS: From
      1979 to 2014, noise exposure has decreased. Measurements taken before the
      implementation of MSHA's revised noise regulation in 2000 were on average 4.5 dBA
      higher than after the law was implemented. Both models produced exposure
      predictions that were less than 1 dBA different than the holdout data.
      CONCLUSION: Overall noise levels in mines have been decreasing. However, this
      decrease has not been uniform across all mining sectors. The exposure predictions
      from the model will be useful to help predict hearing loss in workers in the
      mining industry.

PMID- 27871189
TI  - Determination of 1,2/1,3-diglycerides in Sicilian extra-virgin olive oils by 1H
      NMR over a one-year storage period.
AB  - This study is aimed to monitor by 1H NMR spectroscopy the effect of a 12-month
      storage period on the 1,2-diglycerides over 1,3-diglycerides ratio for five mono
      cultivar 'extra virgin olive oils' (EVOO) (Arbequina, Arbosana, Cerasuola,
      Nocellara and FS17) and one blend of two different cultivars (Nocellara +
      Biancolilla) preserved in the dark and at room temperature. These
      quantifications, at 500 MHz, are readily extracted through a specific and
      original integration difference method. Albeit it was known that the
      isomerisation rate is affected by the free acidity, we here demonstrate that it
      also depends on the presence of specific macromolecules (lipases), indeed,
      different EVOO cultivars with similar free acidity, show different isomerisation
      rate. Our results are consistent with similar diglyceride monitoring performed on
      Greek and Spanish EVOOs by 31P NMR.

PMID- 27871190
TI  - The significance of social rules in group training sessions.
AB  - PURPOSE: To identify what types of social rules are involved in group
      interventions led by physiotherapists (PTs), and how these rules influence
      individual recovery. METHODS: Eight patients; six women and two men, which had
      recently undergone elective hip or knee replacement surgery, were recruited as
      informants from an intervention group that investigated effect of task specific
      exercise. The data comprise observational notes from group training sessions and
      one-on-one semi-structured interviews with the eight patients. Observational
      notes contributed to the development of the research questions. The interviews
      were audio-recorded and transcribed, and a theoretically-oriented analytical
      approach guided by performance theory was conducted to identify the rules.
      RESULTS: Several implicit rules for behavior when attending this group
      intervention were identified. The compulsory style enhances recovery in an
      explicit manner. CONCLUSION: When giving advice and home exercise PTs must
      acknowledge that the roles patients are subtly exposed to during the actual
      clinical encounter are probably quite different from the roles the patients can
      merge into outside the therapy context. This might shed some light on the notion
      of patient adherence/concordance. The significance of social rules in group
      training sessions. Implications for Rehabilitation Health professionals should be
      aware of the implicit social regulations of the clinical encounter. They will
      influence whether and how patients adhere to advice. By acknowledging that
      patients have different roles to merge into, depending on context, health
      professionals may significantly broaden our understanding of patient adherence
      and compliance. The social rules identified in this study contribute to
      individual recovery processes. We encourage health professionals to regard "group
      dynamics" as something that is going on during the group session, and worthwhile
      taking advantage of when planning and implementing group interventions.

PMID- 27871191
TI  - Second trimester medical abortion with mifepristone followed by unlimited dosing
      of buccal misoprostol in Armenia.
AB  - OBJECTIVES: The aim of the study was to assess the efficacy and acceptability of
      a regimen using mifepristone and buccal misoprostol with unlimited dosing for
      second trimester abortion in Armenia. METHODS: Women seeking to terminate 13-22
      week pregnancies were enrolled in the study. Participants swallowed 200 mg
      mifepristone in the clinic and were instructed to return to the hospital for
      induction 24-48 h later. During induction, women were given 400 MUg buccal
      misoprostol every 3 h until the fetus and placenta were expelled. The abortion
      was considered a success if complete uterine evacuation was achieved without
      oxytocin or surgery. RESULTS: A total of 120 women with a median gestational age
      of 18 weeks participated in the study. All women began misoprostol induction
      around 24 h after taking mifepristone. Complete uterine evacuation was achieved
      in 119 (99.2%) women. The median induction-to-abortion interval was 10.3 h (range
      4-17.4) with a mean of 9.5 +/- 2.5 h. A median of four misoprostol doses (range 2
      6) with a mean of 4 +/- 1 misoprostol doses were administered. The induction-to
      abortion interval, number of misoprostol doses, pain score and analgesia use
      increased as gestational age advanced. Acceptability of the method was high among
      both patients and providers. CONCLUSION: The medical abortion regimen of 200 mg
      mifepristone followed 24 h later by induction with 400 MUg buccal misoprostol
      administered every 3 h, with no limit on the number of doses used for the
      termination of pregnancies of 13-22 weeks' gestation is an effective and
      acceptable option for women.

PMID- 27871192
TI  - Specialised dental care for children with complex disabilities focusing on
      child's functioning and need for general anaesthesia.
AB  - PURPOSE: To describe and analyse dental care and treatment modalities for
      children with complex disabilities from a biopsychosocial perspective, with
      special focus on dental treatment under general anaesthesia (GA) and its
      relationship to child's functioning. METHOD: An ICF-CY Checklist for Oral Health
      was completed using structured interview, direct observations, and dental records
      for patients attending a specialist paediatric dentistry clinic. Descriptive and
      comparative data analysis was performed. Performance qualifiers from the ICF-CY
      component Activities and participation were used to calculate functional factors.
      RESULTS: Median referral age was 1.5 years and the majority were referred by
      their paediatrician. Almost all visited a dental hygienist regularly. Dental
      treatment under GA was common and was combined in 78% of sessions with medical
      treatment. Children with limitations in their interpersonal interactions and
      relationships were most likely to have dental GA. CONCLUSION: Children without
      caries experience had been referred for specialist dental care at an earlier age
      than children with caries experience. GA was a common treatment modality and
      dental and medical treatments were coordinated under the same GA for a majority
      of children. By using the ICF-CY, it was possible to identify functional
      limitations characterising children with disabilities that require dental
      treatment under GA. Implications for Rehabilitation Early referral to a
      specialist in paediatric dentistry is valuable for oral disease prevention in
      children with disabilities. Availability of dental treatment under general
      anaesthesia (GA) is also important. Combining dental and medical interventions
      during the same GA session optimises resources both for the individual and for
      the health organisation. Children with limitations in interpersonal interactions
      and relationships are more likely to need dental treatment under GA than other
      children.

PMID- 27871193
TI  - Physiotherapist-delivered cognitive-behavioural interventions are effective for
      low back pain, but can they be replicated in clinical practice? A systematic
      review.
AB  - PURPOSE: To determine if physiotherapist-led cognitive-behavioural (CB)
      interventions are effective for low back pain (LBP) and described sufficiently
      for replication. METHOD: Randomised controlled trials (RCTs) of patients with LBP
      treated by physiotherapists using a CB intervention were included. Outcomes of
      disability, pain, and quality of life were assessed using the GRADE approach.
      Intervention reporting was assessed using the Template for Intervention
      Description and Replication. RESULTS: Of 1898 titles, 5 RCTs (n = 1390) were
      identified. Compared to education and/or exercise interventions, we found high
      quality evidence that CB had a greater effect (SMD; 95% CI) on reducing
      disability (-0.19; -0.32, -0.07), pain (-0.21; -0.33, -0.09); and moderate
      quality evidence of little difference in quality of life (-0.06; -0.18 to 0.07).
      Sufficient information was provided on dose, setting, and provider; but not
      content and procedural information. Studies tended to report the type of CB
      component used (e.g., challenging unhelpful thoughts) with little detail on how
      it was operationalised. Moreover, access to treatment manuals, patient materials
      and provider training was lacking. CONCLUSIONS: With additional training,
      physiotherapists can deliver effective CB interventions. However, without
      training or resources, successful translation and implementation remains
      unlikely. Researchers should improve reporting of procedural information, provide
      relevant materials, and offer accessible provider training. Implications for
      Rehabilitation Previous reviews have established that traditional biomedical
      based treatments (e.g., acupuncture, manual therapy, massage, and specific
      exercise programmes) that focus only on physical symptoms do provide short-term
      benefits but the sustained effect is questionable. A cognitive-behavioural (CB)
      approach includes techniques to target both physical and psychosocial symptoms
      related to pain and provides patients with long-lasting skills to manage these
      symptoms on their own. This combined method has been used in a variety of
      settings delivered by different health care professionals and has been shown to
      produce long-term effects on patient outcomes. What has been unclear is if these
      programmes are effective when delivered by physiotherapists in routine
      physiotherapy settings. Our study synthesises the evidence for this context. We
      have confirmed with high-quality evidence that with additional training,
      physiotherapists can deliver CB interventions that are effective for patients
      with back pain. Physiotherapists who are considering enhancing their treatment
      for patients with low back pain should consider undertaking some additional
      training in how to incorporate CB techniques into their practice to optimise
      treatment benefits and help patients receive long-lasting treatment effects.
      Importantly, our results indicate that using a CB approach, including a variety
      of CB techniques that could be easily adopted in a physical therapy setting,
      provides greater benefits for patient outcomes compared to brief education,
      exercise or physical techniques (such as manual therapy) alone. This provides
      further support that a combined treatment approach is likely better than one
      based on physical techniques alone. Notably, we identified a significant barrier
      to adopting any of these CB interventions in practice. This is because no study
      provided a description of the intervention or accessible training materials that
      would allow for accurate replication. Without access to provider training and/or
      resources, we cannot expect this evidence to be implemented in practice with
      optimal effects. Thus, we would urge physiotherapists to directly contact authors
      of the studies for more information on how to incorporate their interventions
      into their settings.

PMID- 27871195
TI  - What psychological and physical changes predict patients' attainment of
      personally meaningful goals six months following a CBT based pain management
      intervention?
AB  - PURPOSE: To examine the influence of demographic measures, and changes in
      physical ability, pain, self-efficacy and emotional distress on Goal Attainment
      Scaling (GAS) scores, after a 15-day CBT based pain management programme. METHOD:
      Chronic pain patients (N = 257) were referred; 225 (88%) completed the programme
      and were invited for follow up six months later. One hundred and sixty-two (63%),
      (mean age 47.7, 71% female) completed the reassessment procedures. GAS scores
      (which were also repeated at the end the programme), an 11-point Pain Numerical
      Rating Scale, Pain Self-Efficacy Questionnaire, Hospital Anxiety and Depression
      Scale, distance walked in 5 mins, number of sit/stand repetitions in 1 min and
      number of stairs climbed in 1 min were measured on the first day and six months
      following the programme. RESULTS: At six months post discharge, changes in goal
      attainment, physical measures, pain intensity, depression and self-efficacy were
      observed. Hierarchical regression showed change in GAS was predicted by
      improvement in walking tolerance and self-efficacy. CONCLUSIONS: The achievement
      of personally important goals was most significantly associated with change in
      walking ability and self-efficacy, while controlling for the influence of change
      in pain. Implications for Rehabilitation Chronic pain can reduce psychological
      and physical functioning, leading to a reduction in meaningful activities.
      Achievement of personally important activities as measured by Goal Attainment
      Scaling can be a more sensitive measure of programme outcome than that captured
      by many other standard measures. Self-efficacy is an important predictor of
      attainment of patient preferred goals following a CBT based pain management
      programme, and could be emphasized during treatment along with improved walking
      ability, to enhance patients' goal achievement.

PMID- 27871194
TI  - Lipopolysaccharide reduces food passage rate from the crop by a prostaglandin
      independent mechanism in chickens.
AB  - 1. We examined the effect of lipopolysaccharide (LPS), a component of Gram
      negative bacteria, on food passage in the digestive tract of chickens (Gallus
      gallus) in order to clarify whether bacterial infection affects food passage in
      birds. 2. Food passage in the crop was significantly reduced by intraperitoneal
      (IP) injection of LPS while it did not affect the number of defecations,
      suggesting that LPS may affect food passage only in the upper digestive tract. 3.
      Similar to LPS, prostaglandin E2 (PGE2), one of the mediators of LPS, also
      reduced crop-emptying rate in chickens while it had no effect on the number of
      defecations. 4. Pretreatment with indomethacin, which is an inhibitor of
      cyclooxygenase (COX), a prostaglandin synthase, had no effect on LPS-induced
      inhibition of crop emptying. 5. IP injection of LPS did not affect the mRNA
      expression of COX2 in the upper digestive tract of chickens. 6. It is therefore
      likely that LPS and PGE2 reduced food passage rate in the crop by a prostaglandin
      independent pathway in chickens.

PMID- 27871196
TI  - Standardised anatomical alignment of the head in a clinical photography studio. A
      comparison between the Frankfort Horizontal and the natural head position.
AB  - The Frankfort Horizontal (FH) is used by clinical photographers as a reference
      plane to help maintain Standardised Representational Photography (SRP) when
      photographing a patients head. A comparative method of alignment is the Natural
      Head Position (NHP). For this study a survey was created that asked consultants
      and clinical photographers which method of alignment they considered to be the
      most effective. The survey found that 77% of respondents thought the FH was the
      most effective method of alignment. This high figure is due to some confirmation
      bias as the FH is the industry standard.

PMID- 27871197
TI  - Left ventricular assist device-induced reverse remodeling: it's not just about
      myocardial recovery.
AB  - INTRODUCTION: The abnormal structure, function and molecular makeup of dilated
      cardiomyopathic hearts can be partially normalized in patients supported by a
      left ventricular assist device (LVAD), a process called reverse remodeling. This
      leads to recovery of function in many patients, though the rate of full recovery
      is low and in many cases is temporary, leading to the concept of heart failure
      remission, rather than recovery. Areas covered: We summarize data indicative of
      ventricular reverse remodeling, recovery and remission during LVAD support. These
      terms were used in searches performed in Pubmed. Duplication of topics covered in
      depth in prior review articles were avoided. Expert commentary: Although most
      patients undergoing mechanical circulatory support (MCS) show a significant
      degree of reverse remodeling, very few exhibit sufficiently improved function to
      justify device explantation, and many from whom LVADs have been explanted have
      relapsed back to the original heart failure phenotype. Future research has the
      potential to clarify the ideal combination of pharmacological, cell, gene, and
      mechanical therapies that would maximize recovery of function which has the
      potential to improve exercise tolerance of patients while on support, and to
      achieve a higher degree of myocardial recovery that is more likely to persist
      after device removal.

PMID- 27871199
TI  - Influence of obesity and hormone disturbances on sexuality of women in the
      menopause.
AB  - OBJECTIVE: To assess influence of obesity and hormone disturbances on sexuality
      in the menopause. METHODS: The study included 73 menopausal women, who were
      divided into groups according to body mass index (BMI) >= 26.7 kg/m2.
      Anthropometric characteristics and blood pressure were measured. Blood was taken
      at 08:00 for hormones. All the participants filled in McCoy Female Sexual
      Questionnaire for the assessment of sexual life. STATISTICS: Student's t-test,
      correlation, analysis of variance (ANOVA). RESULTS: Follicle-stimulating hormone
      (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) were very
      significantly lower in obese compared to controls. E2 and systolic blood pressure
      were very significantly, while diastolic blood pressure significantly higher in
      obese compared to controls. Obese women had significantly decreased frequency of
      pain during sexual intercourse (3.48 +/- 2.64 vs. 4.09 +/- 2.81). Influence of
      age on frequency of sexual intercourse was very significant. Significant
      influence in interaction between BMI and age on frequency of sexual fantasies as
      well as significant influence of BMI on satisfaction with partner as lover is
      also found. CONCLUSION: Obesity has influence on different aspects of sexuality
      in the postmenopausal women. Our results suggest the need of awareness toward
      obesity and its impact on sexuality in the menopause.

PMID- 27871198
TI  - "It is easier for me to shoot up": stigma, abandonment, and why HIV-positive drug
      users in Russia fail to link to HIV care.
AB  - Many HIV-positive people who inject drugs (PWID) globally are not receiving HIV
      care. This represents a major challenge among key populations to end the global
      HIV epidemic. This qualitative study explored the process and associated barriers
      of linking HIV-positive PWID who are in addiction treatment to HIV care in St.
      Petersburg, Russia. We conducted three focus groups and seven semi-structured
      interviews with participants in the LINC ("Linking Infectious and Narcology
      Care") project at addiction and HIV hospitals in St. Petersburg. The sample
      consisted of 25 HIV-infected patients with opioid dependence and seven health
      care providers, including addiction and infectious disease physicians and case
      managers. A variety of intertwining factors influence effective engagement of
      PWID with HIV treatment. Stigma, problematic patient-provider relationships, and
      fragmented health care were the main challenges for HIV care initiation by PWID,
      which were further exacerbated by injection drug use. Effective linkage of PWID
      to HIV care requires acknowledging and addressing stigma's role and different
      perspectives of patients and providers.

PMID- 27871201
TI  - First-trimester reference centiles of fetal biometry in Indian population.
AB  - AIM AND OBJECTIVE: To create crown-rump length (CRL)-based biometric chart for
      fetus in the first trimester among the Indian population. MATERIAL AND METHODS:
      Cross-sectional data were obtained from 400 singleton pregnancies between 11 and
      14 weeks gestation with a normal outcome. Linear regression models were
      constructed; the mean and SD were derived as a function of CRL. RESULTS: There
      was a positive correlation of CRL with nuchal translucency (NT) (y = 0.0102x +
      0.6307 R2 = 0.1177), biparietal diameter (BPD) (BPD = 0.032*CRL +0.185 R2 =
      0.765), occipito-frontal diameter (OFD), lateral ventricular diameter (LV),
      abdominal circumference (AC) (AC = 0.944*CRL +9.684 R2 = 0.668), femur length
      (FL) (FL = 0.222*CRL -4.734 R2 = 0.661), fetal weight (FW) (FW = 1.328*CRL -10.41
      R2 = 0.662). The regression models and centile charts of NT, BPD, OFD, LV, AC,
      and FW were constructed. Taking FW as the independent variable, a linear equation
      of BPD, AC, and FL to calculate weight was constructed. CONCLUSIONS: The first
      trimester centile charts of fetal parameters can be used as a reference for
      Indian population in the determination of gestational age or other adverse
      outcomes.

PMID- 27871202
TI  - Corticobasal syndrome due to sporadic Creutzfeldt-Jakob disease: a review and
      neuropsychological case report.
AB  - OBJECTIVE: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive, and
      fatal neurodegenerative disease with neuropsychological sequelae. This study
      highlighted a rare presentation of CJD (e.g. corticobasal syndrome [CBS]),
      reviewed updated diagnostic criteria and procedures for CJD (e.g. diffusion
      weighted imaging [DWI], real-time quaking-induced conversion [RT-QuIC]), and
      discussed differential diagnoses. METHOD: Case report methodology focused on a 68
      year-old, Hispanic, right-handed man with 11 years of education. He presented
      with a 1-2-month history of gait and motor difficulties (e.g. rigidity,
      myoclonus). RESULTS: After evaluation, a 'cortical ribboning' pattern on DWI and
      positive RT-QuIC was integrated with performance on neurobehavioral exam (i.e.
      alien limb phenomenon, unilateral ideomotor apraxia) and neuropsychological
      testing (i.e. frontal-parietal dysfunction pattern) to reach a diagnosis of sCJD
      CBS. The patient expired 3 months after onset of symptoms. CONCLUSIONS: This
      literature review and case report highlighted the importance of staying abreast
      of developments in neurological literature and the added value of
      neuropsychology, when integrated with newer procedures, for confirming and
      excluding diagnostic considerations.

PMID- 27871203
TI  - Predicting periviable birthweight and survival: bedside ultrasound versus anatomy
      scan gestational adjusted age projection.
AB  - OBJECTIVE: Two methods of birthweight (BW) prediction in the periviable period:
      bedside ultrasound proximate to delivery versus gestation-adjusted-projection
      (GAP) method was compared. METHODS: Periviable births were identified over a 6
      year period. The GAP method was applied to the estimated fetal weight (EFW) from
      anatomy scans and the gestational age at delivery to predict BW, designated
      EFWGAP. EFW from the bedside ultrasound (EFWUS), and the EFWGAP were compared to
      actual BW to calculate absolute values of error in BW estimates. Neonatal
      survival estimates were made utilizing a National Institute of Child Health and
      Human Development calculator. RESULTS: EFWUS was more accurate than EFWGAP in
      predicting BW as the mean absolute value of error with bedside ultrasound |EFWUS
      BW| was significantly lower than mean absolute value of error with GAP method
      |EFWGAP-BW|, 75.32 +/- 74.64 g versus 125.68 +/- 130.62 g, p = 0.01. Predicted
      neonatal survival based on EBWUS was closer to reference than predicted survival
      based on EBWGAP 9.66% +/- 9.43% versus 7.76% +/- 7.78% p = 0.26. CONCLUSIONS:
      EFWUS is more accurate than EFWGAP for predicting BW in this period. However, the
      GAP technique could have utility in survival predictions when timely performance
      of ultrasound is not feasible.

PMID- 27871204
TI  - DNA barcoding of a colonial ascidian, Lissoclinum fragile (Van Name, 1902).
AB  - Ascidians (tunicates) are marine benthic organisms possessing various
      pharmacological activities, including anti-oxidant, anti-tumour, antimicrobial,
      etc. They also play a key role as model organisms to study various
      neurobehavioral disorders. Ascidian diversity is reportedly less in India due to
      lack of taxonomists as well as the limitations in morphology based taxonomy.
      Molecular taxonomy, comprising the sequencing of cytochrome c oxidase 1 gene
      (barcode region) otherwise known as DNA barcoding reduces these bottlenecks.
      Since several species of the family Didemnidae closely resemble in morphology,
      the present study was aimed to develop DNA barcodes of a colonial ascidian,
      Lissoclinum fragile belonging to the family Didemnidae. CO1 gene of L. fragile
      from Thoothukudi, Mandapam, and Vizhinjam waters were sequenced and submitted in
      GenBank, NCBI through Barcode submission tool. BLAST results showed maximum
      identity (97-100%) for L. fragile collected from different stations. The pairwise
      genetic distances within species and genera were calculated using Kimura two
      parameter (K2P) and the phylogenetic tree was constructed using Neighbour-Joining
      Tree.

PMID- 27871200
TI  - Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disorder
      characterized by focal pathologic bone resorption due to excessive activity of
      osteoclasts (OC). Receptor activator of nuclear factor kappa B ligand (RANKL) is
      essential for the proliferation, differentiation, and survival of OC. Denosumab
      (DMab) is a humanized monoclonal antibody that binds to RANKL with high affinity
      and blocks its subsequent association with its receptor RANK on the surface of OC
      precursors. Area covered: The authors review the molecular and cellular
      mechanisms underlying therapeutic applications of DMab, provide recent highlights
      on pharmacology, efficacy and safety of DMab, and discuss the potential of DMab
      as a novel therapeutic option for the treatment of rheumatoid arthritis. Expert
      opinion: Clinical results suggest that DMab is efficient both in systemic and
      articular bone loss in RA with limited side effects. Diminished bone erosion
      activity was also noted in RA patients on corticosteroids and bisphosphonates.
      Combination of DMab with an anti-TNF agent was not associated with increased
      infection rates. Collectively, these data indicate that DMab, in combination with
      methotrexate and possibly other conventional synthetic Disease Modifying Anti
      Rheumatic Drugs (csDMARDs), is an effective, safe and cost-effective option for
      the treatment of RA.

PMID- 27871205
TI  - The effects of two different swimming training periodization on physiological
      parameters at various exercise intensities.
AB  - This study analysed the effects of two different periodization strategies on
      physiological parameters at various exercise intensities in competitive swimmers.
      Seventeen athletes of both sexes were divided to two groups, the traditional
      periodization (TPG, n = 7) and the reverse periodization group (RPG, n = 10).
      Each group followed a 10-week training period based on the two different
      periodization strategies. Before and after training, swimming velocity (SV),
      energy expenditure (EE), energy cost (EC) and percentage of aerobic (%Aer) and
      anaerobic (%An) energy contribution to the swimming intensities corresponding to
      the aerobic threshold (AerT), the anaerobic threshold (AnT) and the velocity at
      maximal oxygen uptake (vVO2max) were measured. Both groups increased the %An at
      the AerT and AnT intensity (P <= .05). In contrast, at the AnT intensity, EE and
      EC were only increased in TPG. Complementary, %Aer, %An, EE and EC at vVO2max did
      not alter in both groups (P > .05); no changes were observed in SV in TPG and RPG
      at all three intensities. These results indicate that both periodization schemes
      confer almost analogous adaptations in specific physiological parameters in
      competitive swimmers. However, given the large difference in the total training
      volume between the two groups, it is suggested that the implementation of the
      reverse periodization model is an effective and time-efficient strategy to
      improve performance mainly for swimming events where the AnT is an important
      performance indicator.

PMID- 27871207
TI  - Gesturing more diminishes recall of abstract words when gesture is allowed and
      concrete words when it is taboo.
AB  - Gesture during speech can promote or diminish recall for conversation content. We
      explored effects of cognitive load on this relationship, manipulating it at two
      scales: individual-word abstractness and social constraints to prohibit gestures.
      Prohibited gestures can diminish recall but more so for abstract-word recall.
      Insofar as movement planning adds to cognitive load, movement amplitude may
      moderate gesture effects on memory, with greater permitted- and prohibited
      gesture movements reducing abstract-word recall and concrete-word recall,
      respectively. We tested these effects in a dyadic game in which 39 adult
      participants described words to confederates without naming the word or five
      related words. Results supported our expectations and indicated that memory
      effects of gesturing depend on social, cognitive, and motoric aspects of
      discourse.

PMID- 27871206
TI  - Brucellosis and thrombosis of the inferior vena cava.
AB  - We describe the case of a 23-year old woman with a newly diagnosed thrombosis of
      the inferior vena cava associated with a Brucella melitensis infection. We
      suggest possible mechanisms leading to brucellosis-associated venous thrombosis
      and review 14 previously reported cases.?.

PMID- 27871208
TI  - Identification of fraud (with pig stuffs) in chicken-processed meat through
      information of mitochondrial cytochrome b.
AB  - This study was conducted to find out the fraud in chicken-processed meat
      ingredients to protect consumers from commercial adulteration and authentication
      through a reliable way: direct amplification of conserved segment of cytochrome b
      gene of mitochondrial DNA, in addition, using species-specific primer assay for a
      certain cytochrome b. The results reported that chicken-processed meats were
      identified as a chicken meat based on amplification of conserved cytochrome b
      gene of mtDNA, while different fragments sizes were produced after the
      application of species-specific primer as follows: 227, 157, 274, 331, 389 and
      439 bp for raw meat of chicken, goat, cattle, sheep, pig and horse, respectively.
      The results revealed that all chicken meat products are produced with 227 bp in
      size. While, an adulteration with pork stuffs was observed in some of the chicken
      meat products using a species-specific primer of cytochrome b gene, namely,
      chicken luncheon and chicken burger. This study represents a reliable technique
      that could be used to provide a promising solution for identifying the commercial
      adulteration and substitutions in processed meat in retail markets.

PMID- 27871209
TI  - Work-family conflict and neck and back pain in surgical nurses.
AB  - OBJECTIVE: Surgical nurses' work is physically and mentally demanding, possibly
      leading to work-family conflict (WFC). The current study tests WFC to be a risk
      factor for neck and lower back pain (LBP). Job influence and social support are
      tested as resources that could buffer the detrimental impact of WFC. METHODS:
      Forty-eight surgical nurses from two university hospitals in Germany and
      Switzerland were recruited. WFC was assessed with the Work-Family Conflict Scale.
      Job influence and social support were assessed with the Copenhagen Psychosocial
      Questionnaire, and back pain was assessed with the North American Spine Society
      Instrument. RESULTS: Multiple linear regression analyses confirmed WFC as a
      significant predictor of cervical pain (beta = 0.45, p < 0.001) and LBP (beta =
      0.33, p = 0.012). Job influence and social support did not turn out to be
      significant predictors and were not found to buffer the impact of WFC in
      moderator analyses. CONCLUSION: WFC is likely to affect neck and back pain in
      surgery nurses. Work-life interventions may have the potential to reduce WFC in
      surgery nurses.

PMID- 27871210
TI  - Para-kala-azar dermal Leishmaniasis cases in Indian subcontinent - A case series.

PMID- 27871212
TI  - Contributions of triggering-receptor-expressed-on-myeloid-cells-2 to neurological
      diseases.
AB  - Recent laboratory and gene sequencing data suggest that variations in receptors
      called the "triggering-receptors-expressed-on-myeloid-cells" (TREMs) are
      implicated in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and
      frontotemporal lobar degeneration. TREM receptors are thought to play a critical
      role in regulating the immune system, inflammation, and certain cellular
      functions. One TREM, in particular, TREM2, is highly expressed on cells of the
      myeloid lineage. The binding of TREM2 to the adapter protein, DNAX activating
      protein of 12 kD (DAP12), in microglial cells has been shown to modulate
      phagocytosis within the nervous system. This review highlights the role of TREM2
      in neurological diseases. Moreover, here we consider potential contributions of
      TREM2 and mechanisms underlying TREM2 activity as contributing to
      neurodegeneration. These findings may provide novel insights and opportunities to
      consider, especially for clinicians, as they diagnose and treat certain
      neurological diseases.

PMID- 27871211
TI  - Registry and health insurance claims data in vascular research and quality
      improvement.
AB  - The expansion of procedures in multidisciplinary vascular medicine has sparked a
      controversy regarding measures of quality improvement. In addition to primary
      registries, the use of health insurance claims data is becoming of increasing
      importance. However, due to the fact that health insurance claims data are not
      collected for scientific evaluation but rather for reimbursement purposes,
      meticulous validation is necessary before and during usage in research and
      quality improvement matters. This review highlights the advantages and
      disadvantages of such data sources. A recent comprehensive expert opinion panel
      examined the use of health insurance claims data and other administrative data
      sources in medicine. Results from several studies concerning the validity of
      administrative data varied significantly. Validity of these data sources depends
      on the clinical relevance of the diagnoses considered. The rate of implausible
      information was 0.04 %, while the validity of the considered diagnoses varied
      between 80 and 97 % across multiple validation studies. A matching study between
      health insurance claims data of the third-largest German health insurance
      provider, DAK-Gesundheit, and a prospective primary registry of the German
      Society for Vascular Surgery demonstrated a good level of validity regarding the
      mortality of endovascular and open surgical treatment of abdominal aortic
      aneurysm in German hospitals. In addition, a large-scale international comparison
      of administrative data for the same disorder presented important results in
      treatment reality, which differed from those from earlier randomized controlled
      trials. The importance of administrative data for research and quality
      improvement will continue to increase in the future. When discussing the internal
      and external validity of this data source, one has to distinguish not only
      between its intended usage (research vs. quality improvement), but also between
      the included diseases and/or treatment procedures. Linkage between primary
      registry data and administrative data could be a reasonable solution to some
      current major issues of validity.?.

PMID- 27871213
TI  - Shifting racial hierarchies: An analysis of residential segregation among multi
      racial and mono-racial groups in the United States.
AB  - Multi-racial (mixed-race) people constitute a growing percentage of the United
      States (US) population. The study reported in this paper used residential
      segregation measures as a proxy for social distance, to examine whether
      segregation levels of multi-racial groups differ from those of mono-racial groups
      in the US in 2010. First, we find that all multi-racial groups considered in the
      study experience lower levels of segregation at county level than their mono
      racial counterparts. However, black-whites and Hispanic-whites experience higher
      levels of segregation than other multi-racial groups. Second, we find region and
      minority composition of counties are associated significantly with segregation
      levels for multi-racial groups, but relative income is not.

PMID- 27871214
TI  - A measure of perceived pain and tobacco smoking interrelations: pilot validation
      of the pain and smoking inventory.
AB  - Mounting evidence indicates that pain can motivate cigarette smoking behavior,
      smokers have reliably endorsed the use of tobacco to cope with pain, and there is
      reason to suspect that pain may impede smoking cessation. Smoking-related outcome
      expectancies are among the best predictors of cigarette consumption and relapse,
      and the goal of this pilot study was to develop a standardized measure of how
      tobacco smokers perceive their pain and smoking behavior to be interrelated (i.e.
      pain as a motivator of smoking, expectancies for smoking as a means of coping
      with pain, and pain as a barrier to quitting). Participants (N = 75) completed an
      online survey that was designed to assess interrelations between pain and tobacco
      smoking. The nine-item Pain and Smoking Inventory (PSI) demonstrated excellent
      internal consistency (alpha = .95). As expected, PSI scores were higher among
      smokers with chronic pain (vs. no pain), and were positively associated with
      established indices of both pain and tobacco smoking dependence. These results
      corroborate the notion that smokers can effectively communicate perceptions of
      interrelations between their pain and smoking behavior. Future research is needed
      to establish reliability and validity of the PSI among larger, more diverse
      samples of smokers with varying levels of pain. Future work should also examine
      PSI scores as predictors of smoking cessation outcomes, and whether PSI data may
      usefully inform the development of tailored interventions for smokers in pain.

PMID- 27871215
TI  - Formulation, characterization, and in vitro/ex vivo evaluation of quercetin
      loaded microemulsion for topical application.
AB  - The aim of this study was to develop a new microemulsion formulation for topical
      application of poorly soluble drug named quercetin. In order to design suitable
      microemulsion system, the pseudo-ternary phase diagrams of microemulsion systems
      were constructed at different surfactant/co-surfactant ratios using tween 80 as
      surfactant, transcutol(r) P as a co-surfactant and oleic acid as an oil phase.
      Some physicochemical properties such as droplet size, density, refractive index,
      electrical conductivity, pH, surface tension, and viscosity of the microemulsion
      systems were measured at 298.15 K. The average hydrodynamic droplet size of the
      optimized microemulsions was obtained by dynamic light scattering method.
      Morphology assessment of the optimized quercetin-loaded microemulsion by
      transmission electron microscopy analysis indicated that the particles have the
      size of about 25 nm and spherical with narrow size distribution. Equilibrium
      solubility, in vitro drug release at a 24 h time period, release kinetic
      evaluation as well as ex vivo permeation and retention of quercetin-loaded
      microemulsions through rat skin has been investigated. The obtained results
      showed a slow release behavior without any transdermal delivery. Most of the
      formulations fitted best with zero-order kinetic model with a non-Fickian
      mechanisms. This study illustrated that the proposed QU-microemulsion has a good
      potential for use in sunscreen formulations. [Formula: see text].

PMID- 27871216
TI  - Intensive or standard: a meta-analysis of blood pressure lowering for cerebral
      haemorrhage.
AB  - The ideal target blood pressure(BP) has remaining controversial for patients with
      cerebral haemorrhage, so we performed a meta-analysis to assess the effects of
      intensive BP lowering therapy. Clinical trials in which acute-phase patients were
      randomly assigned to an intensive BP lowering group or a standard BP lowering
      group were included. The primary outcome was mortality and dependency at 90 days.
      The secondary outcomes were mortality at 90 days, the proportion of cases
      involving haematoma extension during the acute phase and early neurological
      deterioration. Although intensive BP lowering was associated with reduced
      mortality and dependency at 90 days, this result was not statistically
      significant (OR 0.89, 95% CI 0.77-1.02, P=0.09). No differences between the two
      groups were found with respect to the secondary outcomes. Significant differences
      remained absent in sensitivity analyses. The results suggested that intensive BP
      lowering does not affect 90-day outcomes, but appears to be safe.

PMID- 27871217
TI  - Identification of marine traditional Chinese medicine dried seahorses in the
      traditional Chinese medicine market using DNA barcoding.
AB  - Seahorse documented in Chinese pharmacopeia possess important medicinal efficacy
      and are used as an ingredient in traditional Chinese medicines. The growing
      international trade threatens the species. DNA barcoding holds a great
      application potentiality in wildlife conservation and might prevent the illegal
      trade of threatened species. The COI gene was used to identify seahorse, and nine
      Hippocampus species were found in the three large traditional Chinese medicines
      markets of China. All inter-specific genetic variations were larger than 2%. Mean
      genetic distances between species were 17-fold larger than those within the
      species. Phylogenetic tree showed that each species clustered in the appropriate
      branch. All results demonstrated that COI-based barcoding technique could be used
      to identify seahorse species and played a major role in monitoring the seahorse
      trade.

PMID- 27871218
TI  - The validity of the Brain Injury Cognitive Screen (BICS) as a neuropsychological
      screening assessment for traumatic and non-traumatic brain injury.
AB  - OBJECTIVE: The Brain Injury Cognitive Screen (BICS) was developed as an in
      service cognitive assessment battery for acquired brain injury patients entering
      community rehabilitation. The BICS focuses on domains that are particularly
      compromised following TBI, and provides a broader and more detailed assessment of
      executive function, attention and information processing than comparable
      screening assessments. The BICS also includes brief assessments of perception,
      naming, and construction, which were predicted to be more sensitive to
      impairments following non-traumatic brain injury. The studies reported here
      examine preliminary evidence for its validity in post-acute rehabilitation.
      METHOD: In Study 1, TBI patients completed the BICS and were compared with
      matched controls. Patients with focal lesions and matched controls were compared
      in Study 2. Study 3 examined demographic effects in a sample of normative data.
      RESULTS: TBI and focal lesion patients obtained significantly lower composite
      memory, executive function and attention and information processing BICS scores
      than healthy controls. Injury severity effects were also obtained. Logistic
      regression analyses indicated that each group of BICS memory, executive function
      and attention measures reliably differentiated TBI and focal lesion participants
      from controls. Design Recall, Prospective Memory, Verbal Fluency, and Visual
      Search test scores showed significant independent regression effects. Other
      subtest measures showed evidence of sensitivity to brain injury. CONCLUSIONS: The
      study provides preliminary evidence of the BICS' sensitivity to cognitive
      impairment caused by acquired brain injury, and its potential clinical utility as
      a cognitive screen. Further validation based on a revised version of the BICS and
      more normative data are required.

PMID- 27871219
TI  - Relationship between endothelial function of micro- and macrocirculation in
      patients with peripheral arterial disease.
AB  - BACKGROUND: In the pathogenesis of peripheral arterial occlusive disease (PAD),
      different risk factors of atherosclerosis are involved which stimulate the
      development of the functional and morphological deterioration of vessel walls in
      macro- and microcirculation. The endothelial dysfunction (ED) of macrovessels has
      been proven, however, data on ED in microcirculation are sparse. Therefore, we
      have studied the relationship between micro- and macrocirculation in PAD
      patients. PATIENTS AND METHODS: The study included 85 participants: 30 patients
      had PAD without diabetes mellitus, 30 patients had PAD and diabetes mellitus type
      2, and 25 were healthy controls. Flow-mediated dilation (FMD) and endothelium
      independent dilation (NMD) were studied as markers of macrocirculation, while ED
      of microcirculation was determined by peripheral arterial tonometry, which
      enabled calculation of the reactive hyperemia index (RHI). Simultaneously, the
      augmentation index (AI) as a measure of arterial stiffness was calculated.
      RESULTS: In comparison to healthy subjects, PAD patients had reduced FMD (5.7 +/-
      1.3 % vs. 10.0 +/- 2.4 %, p < 0.001) and significantly decreased NMD (11.0 +/-
      2.9 % vs 23.0 +/- 9.0 %, p < 0.001). Low-flow-mediated constriction was not
      significantly different between the groups. In both groups of patients, RHI was
      significantly lower than in the controls (1.75 +/- 0.45 vs. 2.05 +/- 0.54, p =
      0.033). Furthermore, AI as an indicator of arterial stiffness was significantly
      higher in patient groups than in controls. However, there were no significant
      differences between the groups of PAD patients with and without diabetes mellitus
      in indicators of the functional capability of micro- and macrocirculation. An
      interrelationship was shown between risk factors and both FMD and NMD.
      Significant correlation was also found between FMD and RHI, as was a borderline
      correlation between FMD and AI. CONCLUSIONS: In PAD patients with and without
      diabetes, the functional capability of the entire arterial system is
      deteriorated. These patients have ED in micro- and macrocirculation, as well as
      increased arterial stiffness.?.

PMID- 27871220
TI  - Quiet eye training aids the long-term learning of throwing and catching in
      children: Preliminary evidence for a predictive control strategy.
AB  - Quiet eye training (QET) may be a more effective method for teaching children to
      catch than traditional training (TT) methods, but it is unclear if the benefits
      accrued persist in the long term. Thirty children were randomly allocated into a
      QET or TT group and, while wearing a mobile eye tracker, underwent baseline
      testing, training and two retention tests over a period of eight weeks, using a
      validated throw and catch task. During training, movement-related information was
      provided to both groups, while the QET group received additional instruction to
      increase the duration of their targeting fixation (QE1) on the wall prior to the
      throw, and pursuit tracking (QE2) period on the ball prior to catching. In both
      immediate (R1) and delayed (R2, six weeks later) retention tests, the QET group
      had a significantly longer QE1 duration and an earlier and longer QE2 duration,
      compared to the TT group, who revealed no improvements. A performance advantage
      was also found for the QET compared to the TT group at both R1 and R2, revealing
      the relatively robust nature of the visuomotor alterations. Regression analyses
      suggested that only the duration of QE1 predicted variance in catch success post
      training, pointing to the importance of a pre-programming visuomotor strategy for
      successful throw and catch performance.

PMID- 27871221
TI  - Most of the tight positional conservation of transcription factor binding sites
      near the transcription start site reflects their co-localization within
      regulatory modules.
AB  - BACKGROUND: Transcription factors (TFs) form complexes that bind regulatory
      modules (RMs) within DNA, to control specific sets of genes. Some transcription
      factor binding sites (TFBSs) near the transcription start site (TSS) display
      tight positional preferences relative to the TSS. Furthermore, near the TSS, RMs
      can co-localize TFBSs with each other and the TSS. The proportion of TFBS
      positional preferences due to TFBS co-localization within RMs is unknown,
      however. ChIP experiments confirm co-localization of some TFBSs genome-wide,
      including near the TSS, but they typically examine only a few TFs at a time,
      using non-physiological conditions that can vary from lab to lab. In contrast,
      sequence analysis can examine many TFs uniformly and methodically, broadly
      surveying the co-localization of TFBSs with tight positional preferences relative
      to the TSS. RESULTS: Our statistics found 43 significant sets of human motifs in
      the JASPAR TF Database with positional preferences relative to the TSS, with 38
      preferences tight (+/-5 bp). Each set of motifs corresponded to a gene group of
      135 to 3304 genes, with 42/43 (98%) gene groups independently validated by DAVID,
      a gene ontology database, with FDR < 0.05. Motifs corresponding to two TFBSs in a
      RM should co-occur more than by chance alone, enriching the intersection of the
      gene groups corresponding to the two TFs. Thus, a gene-group intersection
      systematically enriched beyond chance alone provides evidence that the two TFs
      participate in an RM. Of the 903 = 43*42/2 intersections of the 43 significant
      gene groups, we found 768/903 (85%) pairs of gene groups with significantly
      enriched intersections, with 564/768 (73%) intersections independently validated
      by DAVID with FDR < 0.05. A user-friendly web site at http://go.usa.gov/3kjsH
      permits biologists to explore the interaction network of our TFBSs to identify
      candidate subunit RMs. CONCLUSIONS: Gene duplication and convergent evolution
      within a genome provide obvious biological mechanisms for replicating an RM near
      the TSS that binds a particular TF subunit. Of all intersections of our 43
      significant gene groups, 85% were significantly enriched, with 73% of the
      significant enrichments independently validated by gene ontology. The co
      localization of TFBSs within RMs therefore likely explains much of the tight TFBS
      positional preferences near the TSS.

PMID- 27871222
TI  - Genome-wide association study (GWAS) reveals the genetic architecture of four
      husk traits in maize.
AB  - BACKGROUND: Maize (Zea mays) husk referring to the leafy outer enclosing the ear,
      plays an important role in grain production by directly contributing
      photosynthate and protecting ear from pathogen infection. Although the
      physiological functions related to husk have been extensively studied, little is
      known about its morphological variation and genetic basis in natural population.
      RESULTS: Here we utilized a maize association panel including 508 inbred lines
      with tropical, subtropical and temperate backgrounds to decipher the genetic
      architecture attributed to four husk traits, i.e. number of layers, length, width
      and thickness. Evaluating the phenotypic diversity at two different environments
      showed that four traits exhibit broadly natural variations and moderate levels of
      heritability with 0.64, 0.74, 0.49 and 0.75 for number, length, width and
      thickness, respectively. Diversity analysis indicated that different traits have
      dissimilar responses to subpopulation effects. A series of significantly positive
      or negative correlations between husk phenotypes and other agronomic traits were
      identified, indicating that husk growth is coordinated with other developmental
      processes. Combining husk traits with about half of a million of single
      nucleotide polymorphisms (SNPs) via genome-wide association study revealed a
      total of 9 variants significantly associated with traits at P < 1.04 * 10-5,
      which are implicated in multiple functional categories, such as cellular
      trafficking, transcriptional regulation and metabolism. CONCLUSIONS: These
      results provide instrumental information for understanding the genetic basis of
      husk development, and further studies on identified candidate genes facilitate to
      illuminate molecular pathways regulating maize husk growth.

PMID- 27871223
TI  - Patients with HFpEF and HFrEF have different clinical characteristics but similar
      prognosis: a retrospective cohort study.
AB  - BACKGROUND: Globally, heart failure (HF) has been recognized as one of the major
      cardiovascular disorder with high morbidity, mortality and considerable social
      impact. In Sub Saharan African countries, HF has turned out as a leading form of
      cardiovascular diseases, and has considerable socioeconomic impact. However,
      there are differences in clinical characteristics and survival status among
      patients with preserved (HFpEF) and reduced (HFrEF) ejection fraction. The aim of
      this study is to outline the clinical characteristics and medication profile,
      assess the survival status and prognostic factors of Ethiopian HF patients with
      HFrEF and HFpEF. METHODS: A retrospective cohort study was carried out and we
      employed medical records of patient's, admitted as a result of HF to the
      University of Gondar Referral Hospital in the period between December 02, 2010
      and December 01, 2015 due to HF. Kaplan Meier curve was used to analyze the
      survival status and log rank test was used to compare the curves. Cox regression
      was used to analyze independent predictors of mortality in all HF patients.
      RESULTS: Of the 850 patients who were admitted due to HF, 311 patients met the
      inclusion criteria. Majority of the patients had HFpEF (52.73%) and tend to be
      women (76.22%). They predominantly had etiologies of valvular and hypertensive
      heart diseases, and took calcium channel blockers and anticoagulants. Conversely,
      patients with HFrEF had etiologies of ischemic heart disease and dilated
      cardiomyopathy and were prescribed angiotensine converting inhibitors (ACEI) and
      beta blockers. Kaplan Meier curves and Log rank test (p = 0.807) showed that
      there was no statistically significant difference in the mortality difference
      among patients with HFpEF and HFrEF. On the other hand, Cox regression analysis
      showed advanced age, lower sodium level, higher creatinine level and absence of
      medications like ACEI, spironolactone and statins independently predicted
      mortality in all HF patients. CONCLUSIONS: Different clinical characteristics
      were found in both groups of HF patients. There was no difference in survival
      outcome between patients with HFrEF and HFpEF.

PMID- 27871224
TI  - Insights into the human mesenchymal stromal/stem cell identity through
      integrative transcriptomic profiling.
AB  - BACKGROUND: Mesenchymal Stromal/Stem Cells (MSCs), isolated under the criteria
      established by the ISCT, still have a poorly characterized phenotype that is
      difficult to distinguish from similar cell populations. Although the field of
      transcriptomics and functional genomics has quickly grown in the last decade, a
      deep comparative analysis of human MSCs expression profiles in a meaningful
      cellular context has not been yet performed. There is also a need to find a well
      defined MSCs gene-signature because many recent biomedical studies show that key
      cellular interaction processes (i.e. inmuno-modulation, cellular cross-talk,
      cellular maintenance, differentiation, epithelial-mesenchymal transition) are
      dependent on the mesenchymal stem cells within the stromal niche. RESULTS: In
      this work we define a core mesenchymal lineage signature of 489 genes based on a
      deep comparative analysis of multiple transcriptomic expression data series that
      comprise: (i) MSCs of different tissue origins; (ii) MSCs in different states of
      commitment; (iii) other related non-mesenchymal human cell types. The work
      integrates several public datasets, as well as de-novo produced microarray and
      RNA-Seq datasets. The results present tissue-specific signatures for adipose
      tissue, chorionic placenta, and bone marrow MSCs, as well as for dermal
      fibroblasts; providing a better definition of the relationship between
      fibroblasts and MSCs. Finally, novel CD marker patterns and cytokine-receptor
      profiles are unravelled, especially for BM-MSCs; with MCAM (CD146) revealed as a
      prevalent marker in this subtype of MSCs. CONCLUSIONS: The improved biomolecular
      characterization and the released genome-wide expression signatures of human MSCs
      provide a comprehensive new resource that can drive further functional studies
      and redesigned cell therapy applications.

PMID- 27871225
TI  - Genomic epidemiology of Lineage 4 Mycobacterium tuberculosis subpopulations in
      New York City and New Jersey, 1999-2009.
AB  - BACKGROUND: Whole genome sequencing (WGS) has rapidly become an important
      research tool in tuberculosis epidemiology and is likely to replace many existing
      methods in public health microbiology in the near future. WGS-based methods may
      be particularly useful in areas with less diverse Mycobacterium tuberculosis
      populations, such as New York City, where conventional genotyping is often
      uninformative and field epidemiology often difficult. This study applies four
      candidate strategies for WGS-based identification of emerging M. tuberculosis
      subpopulations, employing both phylogenomic and population genetics methods.
      RESULTS: M. tuberculosis subpopulations in New York City and New Jersey can be
      distinguished via phylogenomic reconstruction, evidence of demographic expansion
      and subpopulation-specific signatures of selection, and by determination of
      subgroup-defining nucleotide substitutions. These methods identified known
      historical outbreak clusters and previously unidentified subpopulations within
      relatively monomorphic M. tuberculosis endemic clone groups. Neutrality
      statistics based on the site frequency spectrum were less useful for identifying
      M. tuberculosis subpopulations, likely due to the low levels of informative
      genetic variation in recently diverged isolate groups. In addition, we observed
      that isolates from New York City endemic clone groups have acquired multiple non
      synonymous SNPs in virulence- and growth-associated pathways, and relatively few
      mutations in drug resistance-associated genes, suggesting that overall
      pathoadaptive fitness, rather than the acquisition of drug resistance mutations,
      has played a central role in the evolutionary history and epidemiology of M.
      tuberculosis subpopulations in New York City. CONCLUSIONS: Our results
      demonstrate that some but not all WGS-based methods are useful for detection of
      emerging M. tuberculosis clone groups, and support the use of phylogenomic
      reconstruction in routine tuberculosis laboratory surveillance, particularly in
      areas with relatively less diverse M. tuberculosis populations. Our study also
      supports the use of wider-reaching phylogenomic and population genomic methods in
      tuberculosis public health practice, which can support tuberculosis control
      activities by identifying genetic polymorphisms contributing to epidemiological
      success in local M. tuberculosis populations and possibly explain why certain
      isolate groups are apparently more successful in specific host populations.

PMID- 27871226
TI  - Functional validation of novel compound heterozygous variants in B3GAT3 resulting
      in severe osteopenia and fractures: expanding the disease phenotype.
AB  - BACKGROUND: A new disease class of syndromes, described as linkeropathies, which
      are derived from defects in the glycosaminoglycan-linker region as well as
      glycosaminoglycan-side chains of proteoglycans is increasingly being recognized
      as a cause of human disease. Proteoglycans are an essential component of the
      extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis
      broadly occur due to the incorrect addition of side chains. Previously,
      homozygous missense variants within the B3GAT3 gene encoding beta 1,3
      glucuronyltransferase 3(GlcAT-I) responsible for the biosynthesis of
      glycosaminoglycans have been described in 7 individuals. CASE PRESENTATION: In
      this study, a 4-year-old patient with a severe phenotype of osteoporosis,
      hypotonia, joint laxity, fractures, scoliosis, biscuspid aortic valve and myopia
      was referred for next generation sequencing after extensive negative clinical
      testing. Whole exome sequencing was performed on the proband and his unaffected
      parents to identify the molecular basis of his disease. Sequencing revealed
      compound heterozygous variants in B3GAT3: c.1A > G (p.Met1?) and c.671 T > A
      (p.L224Q). Clinical and in vitro functional studies were then completed to verify
      the pathogenicity of the genotype and further characterize the functional basis
      of the patient's disease demonstrating the patient had a decrease both in the
      protein level of B3GAT3 and in the glucuronyltransferase activity when compared
      to control samples. Independent in vitro assessment of each variant confirmed the
      B3GAT3: c.1A > G (p.Met1?) variant is functionally null and the c.671 T > A
      (p.L224Q) missense variant has significantly reduced glucuronyltransferase
      activity (~3% of control). CONCLUSIONS: This is the first report of a patient
      with compound heterozygosity for a null variant in trans with a missense in
      B3GAT3 resulting in a severe phenotype, expanding both the genotypic and
      phenotypic spectrum of B3GAT3-related disease.

PMID- 27871227
TI  - Genome-wide SNP discovery and population structure analysis in pepper (Capsicum
      annuum) using genotyping by sequencing.
AB  - BACKGROUND: Knowledge on population structure and genetic diversity in vegetable
      crops is essential for association mapping studies and genomic selection.
      Genotyping by sequencing (GBS) represents an innovative method for large scale
      SNP detection and genotyping of genetic resources. Herein we used the GBS
      approach for the genome-wide identification of SNPs in a collection of Capsicum
      spp. accessions and for the assessment of the level of genetic diversity in a
      subset of 222 cultivated pepper (Capsicum annum) genotypes. RESULTS: GBS analysis
      generated a total of 7,568,894 master tags, of which 43.4% uniquely aligned to
      the reference genome CM334. A total of 108,591 SNP markers were identified, of
      which 105,184 were in C. annuum accessions. In order to explore the genetic
      diversity of C. annuum and to select a minimal core set representing most of the
      total genetic variation with minimum redundancy, a subset of 222 C. annuum
      accessions were analysed using 32,950 high quality SNPs. Based on Bayesian and
      Hierarchical clustering it was possible to divide the collection into three
      clusters. Cluster I had the majority of varieties and landraces mainly from
      Southern and Northern Italy, and from Eastern Europe, whereas clusters II and III
      comprised accessions of different geographical origins. Considering the genome
      wide genetic variation among the accessions included in cluster I, a second round
      of Bayesian (K = 3) and Hierarchical (K = 2) clustering was performed. These
      analysis showed that genotypes were grouped not only based on geographical
      origin, but also on fruit-related features. CONCLUSIONS: GBS data has proven
      useful to assess the genetic diversity in a collection of C. annuum accessions.
      The high number of SNP markers, uniformly distributed on the 12 chromosomes,
      allowed the accessions to be distinguished according to geographical origin and
      fruit-related features. SNP markers and information on population structure
      developed in this study will undoubtedly support genome-wide association mapping
      studies and marker-assisted selection programs.

PMID- 27871228
TI  - Genome-wide analysis of G-quadruplexes in herpesvirus genomes.
AB  - BACKGROUND: G-quadruplexes are increasingly recognized as regulatory elements in
      human, animal, bacterial and plant genomes. The presence and function of G
      quadruplexes are not well studied among herpesviruses; in particular, there are
      no systematic genome-wide analysis of these important secondary structures in
      herpesvirus genomes. RESULTS: We performed genome-wide analysis of putative
      quadruplex sequences (PQS) in human herpesviruses. We found unusually high PQS
      densities among human herpesviruses. PQS are enriched in the repeat regions and
      regulatory regions of human herpesviruses. Interestingly, PQS densities are
      higher in regulatory regions of immediate early genes compared to early and late
      genes in most herpesviruses. In addition, the majority of genes functionally
      conserved across human herpesviruses contain one or more PQS within the
      regulatory regions. We also describe the existence of unique intramolecular PQS
      repeats or repetitive G-quadruplex motifs in herpesviruses. Functional studies
      confirm a role for G-quadruplexes in regulating the gene expression of human
      herpesviruses. CONCLUSION: The pervasiveness of PQS, their enrichment and
      conservation at specific genomic locations suggest that these structural entities
      may represent a novel class of functional elements in herpesviruses. Our findings
      provide the necessary framework for studies on the biological role of G
      quadruplexes in herpesviruses.

PMID- 27871229
TI  - "The Cango Lyec Project - Healing the Elephant": HIV related vulnerabilities of
      post-conflict affected populations aged 13-49 years living in three Mid-Northern
      Uganda districts.
AB  - BACKGROUND: The protracted war between the Government of Uganda and the Lord's
      Resistance Army in Northern Uganda (1996-2006) resulted in widespread atrocities,
      destruction of health infrastructure and services, weakening the social and
      economic fabric of the affected populations, internal displacement and death.
      Despite grave concerns that increased spread of HIV/AIDS may be devastating to
      post conflict Northern Uganda, empirical epidemiological data describing the
      legacy of the war on HIV infection are scarce. METHODS: The 'Cango Lyec' Project
      is an open cohort study involving conflict-affected populations living in three
      districts of Gulu, Nwoya and Amuru in mid-northern Uganda. Between November 2011
      and July 2012, 8 study communities randomly selected out of 32, were mapped and
      house-to-house census conducted to enumerate the entire community population.
      Consenting participants aged 13-49 years were enrolled and interviewer
      administered data were collected on trauma, depression and socio-demographic
      behavioural characteristics, in the local Luo language. Venous blood was taken
      for HIV and syphilis serology. Multivariable logistic regression was used to
      determine factors associated with HIV prevalence at baseline. RESULTS: A total of
      2954 participants were eligible, of whom 2449 were enrolled. Among 2388
      participants with known HIV status, HIV prevalence was 12.2% (95%CI: 10.8-13.8),
      higher in females (14.6%) than males (8.5%, p < 0.001), higher in Gulu (15.2%)
      than Nwoya (11.6%, p < 0.001) and Amuru (7.5%, p = 0.006) districts. In this post
      conflict period, HIV infection was significantly associated with war trauma
      experiences (Adj. OR = 2.50; 95%CI: 1.31-4.79), the psychiatric problems of PTSD
      (Adj. OR = 1.44; 95%CI: 1.06-1.96), Major Depressive Disorder (Adj. OR = 1.89;
      95%CI: 1.28-2.80) and suicidal ideation (Adj. OR = 1.87; 95%CI: 1.34-2.61). Other
      HIV related vulnerabilities included older age, being married, separated,
      divorced or widowed, residing in an urban district, ulcerative sexually
      transmitted infections, and staying in a female headed household. There was no
      evidence in this study to suggest that people with a history of abduction were
      more likely to be HIV positive. CONCLUSIONS: HIV prevalence in this post conflict
      affected population is high and is significantly associated with age, trauma,
      depression, history of ulcerative STIs, and residing in more urban districts.
      Evidence-based HIV/STI prevention programs and culturally safe, gender and trauma
      informed are urgently needed.

PMID- 27871230
TI  - Effect of the ifenprodil administered into rostral anterior cingulate cortex on
      pain-related aversion in rats with bone cancer pain.
AB  - BACKGROUND: To assess the effect of rostral anterior cingulate cortex (rACC)
      administration with ifenprodil (NR2B receptor blocker) on bone cancer pain (BCP)
      related aversion sentiment using the conditioned place avoidance experiments in
      rats. METHODS: A total of 30 male Wistar rats without place preference were
      randomly assigned to three groups: control group (Group C, n = 10), BCP group
      (Group P, n = 10) and ifenprodil group (Group Ifen, n = 10). Three microliter
      MADB-106 cells were inoculated into right tibia bone marrow cavity in group P and
      Ifen, while the same dose of normal saline in group C as a control. Ifenprodil
      was administered into the rACC at the 14th day after inoculation in group Ifen
      and normal saline in group C and P. Mechanical stimulation pain thresholds of the
      rats' right hind paws were measured using Von Frey stimulation method at 1 day
      before injection of the tumor cells and at 3, 7,10, 12 and 14 days after the
      injection. The pain-related aversion in rats with BCP was determined by the
      conditioned place avoidance (CPA) test at 14 days after injection of ifenprodil.
      RESULTS: The mechanical stimulation pain thresholds substantially decreased in
      rats in groups P and Ifen from 10 days to 14 days after the incubation with the
      MADB-106 cells (P < 0.05). There were significant differences in pain thresholds
      in groups P and Ifen compared to group C at 10, 12 and 14 days after inoculation
      (P < 0.05). The percentage of residence time in chamber A was (30 +/- 4%) in
      group P, which was lower than (52 +/- 5%) in group C (P < 0.05). After ifenprodil
      treatment, the percentage time in chamber A increased to (42 +/- 5%), which was
      higher than that in group P and still lower than that in group C (P < 0.05).
      CONCLUSION: Ifenprodil administered into rACC as a selective NR2B antagonist can
      effectively alleviate pain-related aversion sentiment in rats with BCP.

PMID- 27871232
TI  - Lipooligosaccharide locus classes and putative virulence genes among chicken and
      human Campylobacter jejuni isolates.
AB  - BACKGROUND: Campylobacter cause morbidity and considerable economic loss due to
      hospitalization and post infectious sequelae such as reactive arthritis, Guillain
      Barre- and Miller Fischer syndromes. Such sequelae have been linked to C. jejuni
      harboring sialic acid structures in their lipooligosaccharide (LOS) layer of the
      cell wall. Poultry is an important source of human Campylobacter infections but
      little is known about the prevalence of sialylated C. jejuni isolates and the
      extent of transmission of such isolates to humans. RESULTS: Genotypes of C.
      jejuni isolates from enteritis patients were compared with those of broiler
      chicken with pulsed-field gel electrophoresis (PFGE), to study the patterns of
      LOS biosynthesis genes and other virulence associated genes and to what extent
      these occur among Campylobacter genotypes found both in humans and chickens.
      Chicken and human isolates generally had similar distributions of the putative
      virulence genes and LOS locus classes studied. However, there were significant
      differences regarding LOS locus class of PFGE types that were overlapping between
      chicken and human isolates and those that were distinct to each source.
      CONCLUSIONS: The study highlights the prevalence of virulence associated genes
      among Campylobacter isolates from humans and chickens and suggests possible
      patterns of transmission between the two species.

PMID- 27871233
TI  - A retrospective analysis of melioidosis in Cambodian children, 2009-2013.
AB  - BACKGROUND: Melioidiosis, infection by Burkholderia pseudomallei, is an important
      but frequently under-recognised cause of morbidity and mortality in Southeast
      Asia and elsewhere in the tropics. Data on the epidemiology of paediatric
      melioidosis in Cambodia are extremely limited. METHODS: Culture-positive
      melioidosis cases presenting to Angkor Hospital for Children, a non-governmental
      paediatric hospital located in Siem Reap, Northern Cambodia, between 1st January
      2009 and 31st December 2013 were identified by searches of hospital and
      laboratory databases and logbooks. RESULTS: One hundred seventy-three evaluable
      cases were identified, presenting from eight provinces. For Siem Reap province,
      the median commune level incidence was estimated to be 28-35 cases per 100,000
      children <15 years per year. Most cases presented during the wet season, May to
      October. The median age at presentation was 5.7 years (range 8 days-15.9 years).
      Apart from undernutrition, co-morbidities were rare. Three quarters (131/173) of
      the children had localised infection, most commonly skin/soft tissue infection
      (60 cases) or suppurative parotitis (51 cases). There were 39 children with B.
      pseudomallei bacteraemia: 29 (74.4%) of these had clinical and/or radiological
      evidence of pneumonia. Overall mortality was 16.8% (29/173) with mortality in
      bacteraemic cases of 71.8% (28/39). At least seven children did not receive an
      antimicrobial with activity against B. pseudomallei prior to death. CONCLUSIONS:
      This retrospective study demonstrated a considerable burden of melioidosis in
      Cambodian children. Given the high mortality associated with bacteraemic
      infection, there is an urgent need for greater awareness amongst healthcare
      professionals in Cambodia and other countries where melioidosis is known or
      suspected to be endemic. Empiric treatment guidelines should ensure suspected
      cases are treated early with appropriate antimicrobials.

PMID- 27871231
TI  - Transcriptomic and proteomic insights into innate immunity and adaptations to a
      symbiotic lifestyle in the gutless marine worm Olavius algarvensis.
AB  - BACKGROUND: The gutless marine worm Olavius algarvensis has a completely reduced
      digestive and excretory system, and lives in an obligate nutritional symbiosis
      with bacterial symbionts. While considerable knowledge has been gained of the
      symbionts, the host has remained largely unstudied. Here, we generated
      transcriptomes and proteomes of O. algarvensis to better understand how this
      annelid worm gains nutrition from its symbionts, how it adapted physiologically
      to a symbiotic lifestyle, and how its innate immune system recognizes and
      responds to its symbiotic microbiota. RESULTS: Key adaptations to the symbiosis
      include (i) the expression of gut-specific digestive enzymes despite the absence
      of a gut, most likely for the digestion of symbionts in the host's epidermal
      cells; (ii) a modified hemoglobin that may bind hydrogen sulfide produced by two
      of the worm's symbionts; and (iii) the expression of a very abundant protein for
      oxygen storage, hemerythrin, that could provide oxygen to the symbionts and the
      host under anoxic conditions. Additionally, we identified a large repertoire of
      proteins involved in interactions between the worm's innate immune system and its
      symbiotic microbiota, such as peptidoglycan recognition proteins, lectins,
      fibrinogen-related proteins, Toll and scavenger receptors, and antimicrobial
      proteins. CONCLUSIONS: We show how this worm, over the course of evolutionary
      time, has modified widely-used proteins and changed their expression patterns in
      adaptation to its symbiotic lifestyle and describe expressed components of the
      innate immune system in a marine oligochaete. Our results provide further support
      for the recent realization that animals have evolved within the context of their
      associations with microbes and that their adaptive responses to symbiotic
      microbiota have led to biological innovations.

PMID- 27871236
TI  - The timing of administration of intravenous dexmedetomidine during lower limb
      surgery: a randomized controlled trial.
AB  - BACKGROUND: Dexmedetomidine, a selective alpha-2 agonist, has sedative,
      analgesic, and anxiolytic effects without respiratory depression. Dexmedetomidine
      can cause a biphasic cardiovascular response, and induce transient hypertension.
      Hypotension is a common complication of spinal anesthesia. Decreasing anxiety of
      patients before procedure is important for high quality of procedure. This study
      aimed to compare the incidence of hypotension and patients' anxiety and comfort
      levels when dexmedetomidine was intravenously administered before and after
      spinal anesthesia. METHODS: Seventy-four patients with American Society of
      Anesthesiologists physical status classification I or II were randomly allocated
      into two groups. Spinal anesthesia was performed using 12 mg of 0.5% heavy
      bupivacaine. In Group A, 1 MUg/kg of dexmedetomidine was intravenously
      administered for 10 min, followed by the maintenance infusion of dexmedetomidine
      0.2 MUg/kg/hr after 5 min of intrathecal bupivacaine injection. Patients in Group
      B received same dose of dexmedetomidine by intravenous administration before 5
      min of intrathecal bupivacaine injection. Perioperative vital signs, anxiety
      (using the Spielberger's State-Trait Anxiety Inventory) and comfort (using the
      numerical rating scale) were evaluated. RESULTS: The incidence of hypotension was
      significantly lower in Group A (16.1%) than in Group B (48.4%) during infusion of
      dexmedetomidine (p = 0.01). The need for treatment of hypotension is higher in
      Group B than Group A (p = 0.02). The incidence of bradycardia and desaturation
      did not significantly differ between the two groups. There were no statistically
      significant differences regarding the patients' anxiety and comfort. CONCLUSIONS:
      Hypotension is more frequently occurred, and the treatment of hypotension is more
      needed in Group B. The intravenously administration of dexmedetomidine before
      spinal anesthesia has no advantages in hemodynamic status and patients' comfort
      compared to that after spinal anesthesia during lower limb surgery. TRIAL
      REGISTRATION: ClinicalTrials.gov number, NCT02155010 . Retrospectively registered
      on May 22, 2014.

PMID- 27871234
TI  - A genome-wide BAC-end sequence survey provides first insights into sweetpotato
      (Ipomoea batatas (L.) Lam.) genome composition.
AB  - BACKGROUND: Sweetpotato, Ipomoea batatas (L.) Lam., is an important food crop
      widely grown in the world. However, little is known about the genome of this
      species because it is a highly heterozygous hexaploid. Gaining a more in-depth
      knowledge of sweetpotato genome is therefore necessary and imperative. In this
      study, the first bacterial artificial chromosome (BAC) library of sweetpotato was
      constructed. Clones from the BAC library were end-sequenced and analyzed to
      provide genome-wide information about this species. RESULTS: The BAC library
      contained 240,384 clones with an average insert size of 101 kb and had a 7.93
      10.82 * coverage of the genome, and the probability of isolating any single-copy
      DNA sequence from the library was more than 99%. Both ends of 8310 BAC clones
      randomly selected from the library were sequenced to generate 11,542 high-quality
      BAC-end sequences (BESs), with an accumulative length of 7,595,261 bp and an
      average length of 658 bp. Analysis of the BESs revealed that 12.17% of the
      sweetpotato genome were known repetitive DNA, including 7.37% long terminal
      repeat (LTR) retrotransposons, 1.15% Non-LTR retrotransposons and 1.42% Class II
      DNA transposons etc., 18.31% of the genome were identified as sweetpotato-unique
      repetitive DNA and 10.00% of the genome were predicted to be coding regions. In
      total, 3,846 simple sequences repeats (SSRs) were identified, with a density of
      one SSR per 1.93 kb, from which 288 SSRs primers were designed and tested for
      length polymorphism using 20 sweetpotato accessions, 173 (60.07%) of them
      produced polymorphic bands. Sweetpotato BESs had significant hits to the genome
      sequences of I. trifida and more matches to the whole-genome sequences of Solanum
      lycopersicum than those of Vitis vinifera, Theobroma cacao and Arabidopsis
      thaliana. CONCLUSIONS: The first BAC library for sweetpotato has been
      successfully constructed. The high quality BESs provide first insights into
      sweetpotato genome composition, and have significant hits to the genome sequences
      of I. trifida and more matches to the whole-genome sequences of Solanum
      lycopersicum. These resources as a robust platform will be used in high
      resolution mapping, gene cloning, assembly of genome sequences, comparative
      genomics and evolution for sweetpotato.

PMID- 27871235
TI  - Development of the interRAI home care frailty scale.
AB  - BACKGROUND: The concept of frailty, a relative state of weakness reflecting
      multiple functional and health domains, continues to receive attention within the
      geriatrics field. It offers a summary of key personal characteristics, providing
      perspective on an individual's life course. There have been multiple attempts to
      measure frailty, some focusing on physiologic losses, others on specific
      diseases, disabilities or health deficits. Recently, multidimensional approaches
      to measuring frailty have included cognition, mood and social components. The
      purpose of this project was to develop and evaluate a Home Care Frailty Scale and
      provide a grounded basis for assessing a person's risk for decline that included
      functional and cognitive health, social deficits and troubling diagnostic and
      clinical conditions. METHODS: A secondary analysis design was used to develop the
      Home Care Frailty Scale. The data set consisted of client level home care data
      from service agencies around the world. The baseline sample included 967,865
      assessments while the 6-month follow-up sample of persons still being served by
      the home care agencies consisted of 464,788 assessments. A pool of 70 candidate
      independent variables were screened for possible inclusion and 16 problem
      outcomes referencing accumulating declines and clinical complications served as
      the dependent variables. Multiple regression techniques were used to analyze the
      data. RESULTS: The resulting Home Care Frailty Scale consisted of a final set of
      29 items. The items fall across 6 categories of function, movement, cognition and
      communication, social life, nutrition, and clinical symptoms. The prevalence of
      the items ranged from a high of 87% for persons requiring help with meal
      preparation to 3.7% for persons who have experienced a recent decline in the
      amount of food eaten. CONCLUSIONS: The interRAI Home Care Frailty Scale is based
      on a strong conceptual foundation and in our analysis, performed as expected.
      Given the use of the interRAI Home Care Assessment System in multiple, diverse
      countries, the Home Care Frailty Scale will have wide applicability to support
      program planning and policy decision-making impacting home care clients and their
      formal and informal caregivers throughout the world.

PMID- 27871237
TI  - A unique association of arrhythmogenic right ventricular dysplasia and acute
      myocarditis, as assessed by cardiac MRI: a case report.
AB  - BACKGROUND: Arrhythmogenic right ventricular dysplasia (ARVD), is a genetic
      disorder of the heart, which mainly involves the right ventricle. It is
      characterized by hypokinetic areas at the free wall of the right ventricle (RV)
      or both ventricles, where myocardium is replaced by fibrous or fatty tissue. ARVD
      is an important cause of ventricular arrhythmias in children and young adults.
      Although the transmission of the disease is based on hereditary, in young adults
      it may not show any symptoms. The main differential diagnoses with other frequent
      etiological causes of sudden arrhythmia are: idiopathic outflow tract ventricular
      tachycardia of the RV, myocarditis, dilated cardiomyopathy and sarcoidosis. CASE
      PRESENTATION: We describe an unusual case of a 44-year-old woman who was
      hospitalized for ventricular tachycardia, deep asthenia and dyspnoea with no
      previous history of cardiac disease. The patient had a ten-year history of
      palpitations, which started immediately after her last pregnancy. She was
      diagnosed with both acute/subacute viral myocarditis and arrhythmogenic right
      ventricular dysplasia, based on established clinical and cardiac MRI criteria.
      After the diagnosis the patient received an automatic implantable cardioverter
      defibrillator. Currently, she is on clinical follow-up with no apparent further
      complications. CONCLUSION: Analyzing this rare case, we have shown the link
      between myocarditis and arrhythmogenic right ventricular dysplasia, and how
      important is to perform a cardiac MRI, in the context of acute myocarditis and
      ventricular arrhythmia.

PMID- 27871238
TI  - Long chain n-3 polyunsaturated fatty acids and vascular function in patients with
      chronic kidney disease and healthy subjects: a cross-sectional and comparative
      study.
AB  - BACKGROUND: Patients with chronic kidney disease have a markedly increased
      cardiovascular mortality compared with the general population. Long chain n-3
      polyunsaturated fatty acids have been suggested to possess cardioprotective
      properties. This cross-sectional and comparative study evaluated correlations
      between hemodynamic measurements, resistance artery function and fish consumption
      to the content of long chain n-3 polyunsaturated fatty acids in adipose tissue, a
      long-term marker of seafood intake. METHODS: Seventeen patients with chronic
      kidney disease stage 5 + 5d and 27 healthy kidney donors were evaluated with
      hemodynamic measurements before surgery; from these subjects, 11 patients and 11
      healthy subjects had vasodilator properties of subcutaneous resistance arteries
      examined. The measurements were correlated to adipose tissue n-3 polyunsaturated
      fatty acids. Information on fish intake was obtained from a dietary questionnaire
      and compared with adipose tissue n-3 polyunsaturated fatty acids. RESULTS: Fish
      intake and the content of n-3 polyunsaturated fatty acids in adipose tissue did
      not differ between patients and controls. n-3 polyunsaturated fatty acid levels
      in adipose tissue were positively correlated to systemic vascular resistance
      index; (r = 0.44; p = 0.07 and r = 0.62; p < 0.05, chronic kidney disease and
      healthy subjects respectively) and negatively correlated to cardiac output index
      (r = -0.69; p < 0.01 and r = -0.50; p < 0.05, chronic kidney disease and healthy
      subjects respectively). No correlation was observed between n-3 polyunsaturated
      fatty acid levels in adipose tissue and vasodilator properties in resistance
      arteries. n-3 PUFA content in adipose tissue increased with increasing self
      reported fish intake. CONCLUSIONS: The correlations found, suggest a role for n-3
      polyunsaturated fatty acids in hemodynamic properties. However, this is
      apparently not due to changes in intrinsic properties of the resistance arteries
      as no correlation was found to n-3 polyunsaturated fatty acids.

PMID- 27871239
TI  - Lesbian womens' access to healthcare, experiences with and expectations towards
      GPs in German primary care.
AB  - BACKGROUND: Lesbian women have higher rates of physical and psychiatric disorders
      associated with experiences of discrimination, homophobia and difficulties with
      coming out. Therefore, easy access to specialized healthcare in an open
      atmosphere is needed. We aimed to describe women's access to and experiences with
      healthcare in Germany, and to assess the responsibility of the general
      practitioner (GP) compared to other specialities providing primary health care.
      METHODS: A questionnaire study was conducted via internet and paper-based
      sampling. Using current literature, we designed a questionnaire consisting of
      sociodemographic data, sexual orientation, access to care and reasons for
      encounter, disclosure of sexual orientation, experience with the German health
      system (discrimination, homophobia), and psychological burden. Depression was
      assessed using the depression screening from the Patient Health Questionnaire
      (PHQ-2). RESULTS: We obtained responses from 766 lesbian women. Although 89% had
      a primary care physician, only 40% had revealed their sexual orientation to their
      doctor. The main medical contacts were GPs (66%), gynaecologists (10%) or
      psychiatrists (6%). Twenty-three percent claimed they were unable to find a
      primary care physician. Another 12.4% had experienced discrimination. Younger
      lesbian women with higher education levels and who were less likely to be out to
      other physicians were more likely to disclose their sexual orientation to their
      primary care physician. GPs play an important role in healthcare for lesbian
      women, even in a non-gatekeeping healthcare system like Germany. Study
      participants suggested improvements regarding gender neutral language, flyers on
      homosexuality in waiting areas, involvement of partners, training of physicians,
      directories of homosexual physicians and labelling as a lesbian-friendly
      practice. CONCLUSIONS: GPs should create an open atmosphere and acquire the
      respective knowledge to provide adequate treatment. Caring for marginal groups
      should be incorporated in medical training and further education. Ideally,
      physicians address patients' sexual orientation pro-actively in order to address
      individual needs accordingly.

PMID- 27871241
TI  - Prevalence, antimicrobial susceptibility patterns and associated risk factors of
      Shigella and Salmonella among food handlers in Arba Minch University, South
      Ethiopia.
AB  - BACKGROUND: The availability of safe food improves health of the people that
      contributes to productivity and provides an effective platform for development
      and poverty alleviation. On the other hand, unsafe food handling and processing
      can serve as a vehicle for the transmission of a variety of disease causing
      agents. The risk of food getting contaminated depends largely on the health
      status of the food handlers, their personal hygiene, knowledge and practice of
      food hygiene. Food borne diseases are therefore a public health problem in
      developed and developing countries which is also true for Ethiopia. Hence, the
      aim of this study was to determine prevalence, antimicrobial susceptibility
      patterns and associated risk factors of Shigella and Salmonella among food
      handlers in Arba Minch University, South Ethiopia. METHODS: A cross sectional
      study was conducted among food handlers in Arba Minch University students'
      cafeteria from April- June, 2015. Structured questionnaire was used to collect
      socio demographic data and associated risk factors. Stool sample was collected
      and examined for pathogens following standard procedures. Biochemical tests were
      done to identify the species of pathogens and sensitivity test was done using
      Kirby- Baur disk diffusion technique. RESULTS: A total of 376 food handlers were
      enrolled in the study with the response rate of 100% for data collected by
      questionnaire. About 7.4% were aged less than 20 years with majority (63.3%) lay
      in the working age group of 21-35 years. However, a total of 345 food handlers
      participated for stool examination of whom, stool cultures revealed 6.9% of
      Salmonella and 3% Shigella isolates. Finger nail status (AOR=0.033), hand washing
      practice after toilet (AOR= 0.006) and touching food with bare hands (AOR= p <
      0.001) were independent predictors of infectious enteric diseases among the food
      handlers. All isolated pathogens were resistant to amoxicillin (100%), followed
      by clarithromycin (41%) and amoxicillin-clavulanic acid (35%). CONCLUSION: The
      present study showed high prevalence of enteropathogens among the study
      participants. The study also revealed poor personal hygiene like poor practice of
      hand washing. Therefore, pre placement, in service training on personal and food
      hygiene should be provided to all food handlers with regular sanitary inspection
      to improve adherence of food handlers to personal hygiene and food safety
      practices.

PMID- 27871240
TI  - ABO antigen and secretor statuses are not associated with gut microbiota
      composition in 1,500 twins.
AB  - BACKGROUND: Host genetics is one of several factors known to shape human gut
      microbiome composition, however, the physiological processes underlying the
      heritability are largely unknown. Inter-individual differences in host factors
      secreted into the gut lumen may lead to variation in microbiome composition. One
      such factor is the ABO antigen. This molecule is not only expressed on the
      surface of red blood cells, but is also secreted from mucosal surfaces in
      individuals containing an intact FUT2 gene (secretors). Previous studies report
      differences in microbiome composition across ABO and secretor genotypes. However,
      due to methodological limitations, the specific bacterial taxa involved remain
      unknown. RESULTS: Here, we sought to determine the relationship of the microbiota
      to ABO blood group and secretor status in a large panel of 1503 individuals from
      a cohort of twins from the United Kingdom. Contrary to previous reports, robust
      associations between either ABO or secretor phenotypes and gut microbiome
      composition were not detected. Overall community structure, diversity, and the
      relative abundances of individual taxa were not significantly associated with ABO
      or secretor status. Additionally, joint-modeling approaches were unsuccessful in
      identifying combinations of taxa that were predictive of ABO or secretor status.
      CONCLUSIONS: Despite previous reports, the taxonomic composition of the
      microbiota does not appear to be strongly associated with ABO or secretor status
      in 1503 individuals from the United Kingdom. These results highlight the
      importance of replicating microbiome-associated traits in large, well-powered
      cohorts to ensure results are robust.

PMID- 27871242
TI  - Comparison of coronary arterial lumen dimensions on angiography and plaque
      characteristics on optical coherence tomography images and their changes induced
      by statin.
AB  - BACKGROUND: Coronary angiography (CAG) is widely used to assess lumen dimensions,
      and optical coherence tomography (OCT) is used to evaluate the characteristics of
      atherosclerotic plaque. This study was aimed to compare coronary lumen dimensions
      using CAG and plaque characteristics using OCT and their changes during statin
      therapy. METHODS: We identified 97 lipid-rich plaques from 69 statin-naive
      patients, who received statin therapy in the following 12 months. CAG and OCT
      examinations were conducted at baseline and 12-month follow-up period. RESULTS:
      Lesion length, as measured by CAG, was closely correlated with lipid length by
      OCT (baseline: r = 0.754, p < 0.001; follow-up: r = 0.639, p < 0.001). However,
      no significant correlations were found between the other findings on OCT and data
      on CAG. With 12-month statin therapy, microstructures of lipid-rich plaques were
      significantly improved, but CAG-derived lumen dimensions were not improved.
      Moreover, we found no significant relationship between changes in OCT
      measurements and changes in CAG data over time. CONCLUSION: Lipid length on OCT
      and lesion length on CAG were closely correlated. However, plaque microstructural
      characteristics on OCT showed no significantly statistically correlations with
      lumen dimensions on CAG, neither did their evolutionary changes induced by statin
      over time. A RETROSPECTIVELY REGISTERED STUDY: Clinical trial registry:
      ClinicalTrial.gov. Registered number: NCT01023607 . Registered 1 December 2009.

PMID- 27871243
TI  - OsACOS12, an orthologue of Arabidopsis acyl-CoA synthetase5, plays an important
      role in pollen exine formation and anther development in rice.
AB  - BACKGROUND: Sporopollenin is a major component of the pollen exine pattern. In
      Arabidopsis, acyl-CoA synthetase5 (ACOS5) is involved in sporopollenin precursor
      biosynthesis. In this study, we identified its orthologue, OsACOS12, in rice
      (Oryza sativa) and compared the functional conservation of ACOS in rice to
      Arabidopsis. RESULTS: Sequence analysis showed that OsACOS12 shares 63.9 % amino
      acid sequence identity with ACOS5. The osacos12 mutation caused by a pre-mature
      stop codon in LOC_Os04g24530 exhibits defective sexine resulting in a male
      sterile phenotype in rice. In situ hybridization shows that OsACOS12 is expressed
      in tapetal cells and microspores at the transcript level. The localization of
      OsACOS12-GFP demonstrated that OsACOS12 protein is accumulated in tapetal cells
      and anther locules. OsACOS12 driven by the ACOS5 promoter could partially restore
      the male fertility of the acos5 mutant in Arabidopsis. CONCLUSIONS: OsACOS12 is
      an orthologue of ACOS5 that is essential for sporopollenin synthesis in rice.
      ACOS5 and OsACOS12 are conserved for pollen wall formation in monocot and dicot
      species.

PMID- 27871245
TI  - Methicillin resistant Staphylococcus aureus in Ethiopia: a meta-analysis.
AB  - BACKGROUND: The burden of methicillin resistant Staphylococcus aureus is a major
      public health concern worldwide; however the overall epidemiology of multidrug
      resistant strains is neither coordinated nor harmonized, particularly in
      developing countries including Ethiopia. Therefore, the aim of this meta-analysis
      was to assess the burden of methicillin resistant Staphylococcos aureus and its
      antibiotic resistance pattern in Ethiopia at large. METHODS: PubMed, Google
      Scholar, and lancet databases were searched and a total of 20 studies have been
      selected for meta-analysis. Six authors have independently extracts data on the
      prevalence of methicillin resistant Staphylococcus aureus among clinical isolates
      of Staphylococcus aureus. Statistical analysis was achieved by using Open meta
      analyst (version 3.13) and Comprehensive meta-analysis (version 3.3) softwares.
      The overall prevalence of methicillin resistant Staphylococcus aureus and its
      antibiotic resistance pattern were pooled by using the forest plot, table and
      figure with 95% CI. RESULTS: The pooled prevalence of methicillin resistant
      Staphylococcus aureus was 32.5% (95% CI, 24.1 to 40.9%). Moreover, methicillin
      resistant Staphylococcus aureus strains were found to be highly resistant to
      penicillin, ampicillin, erythromycin, and amoxicillin, with a pooled resistance
      ratio of 99.1, 98.1, 97.2 and 97.1%, respectively. On the other hand, comparably
      low levels of resistance ratio were noted to vancomycin, 5.3%. CONCLUSION: The
      overall burden of methicillin resistant Staphylococcus aureus is considerably
      high, besides these strains showed extreme resistance to penicillin, ampicillin,
      erythromycin and amoxicillin. In principle, appropriate use of antibiotics,
      applying safety precautions are the key to reduce the spread of multidrug
      resistant strains, methicillin resistant Staphylococcus aureus in particular.

PMID- 27871246
TI  - Functional characterization of thiolase-encoding genes from Xanthophyllomyces
      dendrorhous and their effects on carotenoid synthesis.
AB  - BACKGROUND: The basidiomycetous yeast Xanthophyllomyces dendrorhous has been
      described as a potential biofactory for terpenoid-derived compounds due to its
      ability to synthesize astaxanthin. Functional knowledge of the genes involved in
      terpenoid synthesis would create opportunities to enhance carotenoid production.
      A thiolase enzyme catalyzes the first step in terpenoid synthesis. RESULTS: Two
      potential thiolase-encoding genes were found in the yeast genome;
      bioinformatically, one was identified as an acetyl-CoA C-acetyltransferase
      (ERG10), and the other was identified as a 3-ketoacyl Co-A thiolase (POT1).
      Heterologous complementation assays in Saccharomyces cerevisiae showed that the
      ERG10 gene from X. dendrorhous could complement the lack of the endogenous ERG10
      gene in S. cerevisiae, thereby allowing cellular growth and sterol synthesis. X.
      dendrorhous heterozygous mutants for each gene were created, and a homozygous
      POT1 mutant was also obtained. This mutant exhibited changes in pigment
      composition and higher ERG10 transcript levels than the wild type strain.
      CONCLUSIONS: The results support the notion that the ERG10 gene in X. dendrorhous
      is a functional acetyl-CoA C-acetyltransferase essential for the synthesis of
      mevalonate in yeast. The POT1 gene would encode a functional 3-ketoacyl Co-A
      thiolase that is non-essential for cell growth, but its mutation indirectly
      affects pigment production.

PMID- 27871247
TI  - Cost-effectiveness of workplace wellness to prevent cardiovascular events among
      U.S. firefighters.
AB  - BACKGROUND: The leading cause of death among firefighters in the United States
      (U.S.) is cardiovascular events (CVEs) such as sudden cardiac arrest and
      myocardial infarction. This study compared the cost-effectiveness of three
      strategies to prevent CVEs among firefighters. METHODS: We used a cost
      effectiveness analysis model with published observational and clinical data, and
      cost quotes for physiologic monitoring devices to determine the cost
      effectiveness of three CVE prevention strategies. We adopted the fire department
      administrator perspective and varied parameter estimates in one-way and two-way
      sensitivity analyses. RESULTS: A wellness-fitness program prevented 10% of CVEs,
      for an event rate of 0.9% at $1440 over 10-years, or an incremental cost
      effectiveness ratio of $1.44 million per CVE prevented compared to no program. In
      one-way sensitivity analyses, monitoring was favored if costs were < $116/year.
      In two-way sensitivity analyses, monitoring was not favored if cost was >=
      $399/year. A wellness-fitness program was not favored if its preventive relative
      risk was >0.928. CONCLUSIONS: Wellness-fitness programs may be a cost-effective
      solution to preventing CVE among firefighters compared to real-time physiologic
      monitoring or doing nothing.

PMID- 27871244
TI  - Identification of genes for engineering the male germline of Aedes aegypti and
      Ceratitis capitata.
AB  - BACKGROUND: Synthetic biology approaches are promising new strategies for control
      of pest insects that transmit disease and cause agricultural damage. These
      strategies require characterised modular components that can direct appropriate
      expression of effector sequences, with components conserved across species being
      particularly useful. The goal of this study was to identify genes from which new
      potential components could be derived for manipulation of the male germline in
      two major pest species, the mosquito Aedes aegypti and the tephritid fruit fly
      Ceratitis capitata. RESULTS: Using RNA-seq data from staged testis samples, we
      identified several candidate genes with testis-specific expression and suitable
      expression timing for use of their regulatory regions in synthetic control
      constructs. We also developed a novel computational pipeline to identify
      candidate genes with testis-specific splicing from this data; use of alternative
      splicing is another method for restricting expression in synthetic systems. Some
      of the genes identified display testis-specific expression or splicing that is
      conserved across species; these are particularly promising candidates for
      construct development. CONCLUSIONS: In this study we have identified a set of
      genes with testis-specific expression or splicing. In addition to their interest
      from a basic biology perspective, these findings provide a basis from which to
      develop synthetic systems to control important pest insects via manipulation of
      the male germline.

PMID- 27871248
TI  - Left ventricle remodeling predicts the recurrence of ventricular tachyarrhythmias
      in implantable cardioverter defibrillator recipients for secondary prevention.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) is an effective
      treatment for secondary prevention of ventricular tachycardia/ventricular
      fibrillation (VT/VF). Left ventricular (LV) remodeling may develop before ICD
      implant and over time. However, it remains unclear how LV remodeling affects
      subsequent risk for recurrence VT/VF in ICD recipients under optimal medical
      therapy. METHODS: From May of 2004 to June of 2015, 144 patients received ICD
      implantation for secondary prevention were enrolled in this study. All
      information interrogated from ICD devices during follow-up or ICD therapy history
      (anti-tachycardia pacing and shock therapy) were reviewed and validated the
      occurrences of VT/VF. RESULTS: At a mean follow-up of 1110.5 +/- 860.6 days, 53
      patients (36.8%) had recurrence of VT/VF episodes and 91 patients had no
      recurrence of VT/VF episode after ICD implant. Left ventricular end-diastolic
      volume (LVEDV) > 163.5 mL had significant predictive value for VT/VF recurrence
      (area under the curve: 0.602, p = 0.041). Moreover, the percentage of patients
      with LVEDV >163.5 mL was significantly higher in patients with recurrent VT/VF
      than patients without recurrent VT/VF (62.3 vs 40.0%, p = 0.010). Left
      ventricular ejection fraction <= 30% (p = 0.031), LVEDV > 163.5 mL (p = 0.012)
      and QRS width > 125 msec (p = 0.049) were significant predictors for VT/VF
      recurrence by univariate Cox regression analysis. However, only LVEDV > 163.5 mL
      (hazard ratio: 2.549, 95% confidence interval: 1.249 ~ 5.201, p = 0.010) and QRS
      width > 125 msec (hazard ratio: 2.173, 95% confidence interval: 1.030 ~ 4.586, p
      = 0.042) were independent predictors for recurrence of VT/VF after multivariable
      adjustment. CONCLUSION: LV remodeling and QRS width > 125 msec were independent
      predictors for VT/VF recurrence in secondary prevention ICD recipients under
      optimal medical therapy, independent of LV ejection fraction.

PMID- 27871249
TI  - Benign clear cell "sugar" tumor of the lung in a patient with Birt-Hogg-Dube
      syndrome: a case report.
AB  - BACKGROUND: Birt-Hogg-Dube (BHD) syndrome is a rare inherited autosomal
      genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a
      tumor suppressor gene of which protein product is involved in mechanistic target
      of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism.
      Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of
      the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal
      neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome,
      although the condition is due to deleterious sequence variants in a tumor
      suppressor gene. Here we report, for the first time to our knowledge, a patient
      with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of
      the lung, a benign tumor belonging to perivascular epithelioid cell tumors
      (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1)
      or 2 (TSC2) gene. CASE PRESENTATION: In a 38-year-old Asian woman, two well
      circumscribed nodules in the left lung and multiple thin-walled, irregularly
      shaped cysts on the basal and medial area of the lungs were disclosed by chest
      roentgenogram and computer-assisted tomography (CT) during a preoperative survey
      for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed
      large polygonal cells with clear cytoplasm proliferating in a solid pattern.
      Immunohistochemistry revealed that these tumor cells were positive for
      microphthalmia-transcription factor, S100, and CD1a but negative for HMB45,
      indicating that the tumor was a CCST. Genetic testing indicated that the patient
      had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7
      nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon
      12 using genomic DNA obtained from her microdissected CCST cells clearly revealed
      loss of the wild-type FLCN sequence, which confirmed complete functional loss of
      the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2
      associated genetic region was demonstrated. CONCLUSION: To our knowledge, this is
      the first report of CCST of the lung in a patient with BHDS, indicating that CCST
      should be added to the spectrum of pulmonary manifestations of BHDS.

PMID- 27871250
TI  - Drug resistance and population structure of M.tuberculosis isolates from prisons
      and communities in Ethiopia.
AB  - BACKGROUND: The population structure and drug resistance pattern of Mycobacterium
      tuberculosis complex (MTBC) isolates in Ethiopian prisons and some communities is
      still unknown. METHODS: A comparative cross sectional study was conducted on 126
      MTBC strains isolated from prisons and communities in southwestern, southern and
      eastern Ethiopia. Phenotypic drug susceptibility testing was performed with the
      MGIT960 system. Combined 24-loci Mycobacterium interspersed repetitive unit
      variable number tandem repeat and spacer oligonucleotide typing methods were used
      to study the MTBC population structure. The obtained data from prisons and
      communities were compared using statistical tests and regression analysis.
      RESULTS: A diverse population structure with 11 different lineages and sub
      lineages was identified. The predominant strains were the recently described
      Ethiopia_H37Rv like (27.52%) and Ethiopia_3 (16.51%) with equal lineage
      distribution between prisons and communities. 28.57% of prison strains and 31.82%
      of community strains shared the identical genotype with at least one other
      strain. The multidrug-resistance (MDR) prevalence of the community was 2.27%
      whereas that of prisons was 9.52%. The highest mono resistance was seen against
      streptomycin (15.89%). CONCLUSION: Tuberculosis in communities and prisons is
      caused by a variety of MTBC lineages with predominance of local Ethiopian
      lineages. The increasing prevalence of MDR MTBC strains is alarming. These
      findings suggest the need for new approaches for control of MDR tuberculosis in
      Ethiopia.

PMID- 27871251
TI  - Epidemiology and RAPD-PCR typing of thermophilic campylobacters from children
      under five years and chickens in Morogoro Municipality, Tanzania.
AB  - BACKGROUND: Campylobacter species are gram negative and flagellated bacteria
      under the genus Campylobacter, family Campylobacteriaceae. These pathogens cause
      zoonotic infections among human and animal populations. This study was undertaken
      between December 2006 and May 2007 to determine prevalence, risk factors and
      genetic diversity of thermophilic Campylobacter isolates from children less than
      5 years and chickens in Morogoro Municipality, Tanzania. METHODS: The Skirrow's
      protocol was used for isolation and identification of Campylobacter from 268
      human stool specimens and 419 chicken cloacal swabs. Patient biodata and risk
      factors associated with human infection were also collected. Genetic diversity of
      Campylobacter isolates was determined by a RAPD-PCR technique using OPA 11 primer
      (5'-CAA TCG CCG T-3'). Phylogenetic analysis and band pattern comparison were
      done by Bionumerics software and visual inspection. RESULTS: Stool samples from
      268 children and 419 cloacal swabs from chickens were analyzed. Prevalence of
      thermophilic Campylobacters in children was 19% with higher isolation frequency
      (p = 0.046) in males (23.5%) than females (13.8%). Campylobacter jejuni (78.4%)
      was more isolated (p = 0.000) than C. coli (19.6%) and 2% were unidentified
      isolates. In chickens, the prevalence was 42.5% with higher isolation rate (p =
      0.000) of C. jejuni (87%) than C. coli (13%). Campylobacters were more frequently
      recovered (p = 0.000) from indigenous/ local chickens (75.0%) followed by
      cockerels (52.2%), broilers (50.0%) and lowest in layers (22.7%). Keeping
      chickens without other domestic animals concurrently (p = 0.000), chicken types
      (p = 0.000) and flock size (p = 0.007) were risk factors for infection in
      chickens. One hundred and fifty two (152) thermophillic Campylobacter isolates
      were genotyped by RAPD-PCR of which 114 were C. jejuni (74 from chickens and 40
      humans) and 38 C. coli (28 from chickens and 10 humans). Comparison of
      Campylobacter isolates from children and chickens revealed high diversity with
      only 6.1% of C. jejuni and 5.3% of C. coli being 100% genetically similar.
      CONCLUSIONS: This study has recorded high prevalence of thermophilic
      Campylobacter in children less than 5 years and chickens in Morogoro
      municipality. The observed genetic similarity among few C. jejuni and C. coli
      isolates from children and chicken suggests existence of cross transmission of
      these pathogens between children under 5 years and chickens.

PMID- 27871252
TI  - Age patterns and transmission characteristics of hand, foot and mouth disease in
      China.
AB  - BACKGROUND: Hand, foot and mouth disease (HFMD) has circulated in China and
      caused yearly outbreak. To understand the transmission of the disease and to
      assess the spatial variation in cases reported, we examined age-specific
      transmission characteristics and reporting rates of HFMD for 31 provinces in
      mainland China. METHODS: We first analyzed incidence spatial patterns and age
      specific incidence patterns using dataset from 2008 to 2012. Transmission
      characteristics were estimated based on catalytic model. Reporting rates were
      estimated using a simple mass action model from "Time Series Susceptible
      Infectious Recovered" (TSIR) modeling. RESULTS: We found age-specific spatial
      incidence patterns: age-specific proportions of HFMD cases varied geographically
      in China; larger case percentage was among children of 3-5 years old in the
      northern part of China and was among children of 0-2 years old in the southern
      part of China. Our analysis results revealed that: 1) reporting rates and
      transmission characteristics including the average age at infection, the force of
      infection and the basic reproduction number varied geographically in China; 2)
      patterns of the age-specific force of infection for 30 provinces were similar to
      that of childhood infections in developed countries; the age group that had the
      highest infection risk was 3-5 years old in 30 provinces, and 10-14 years old in
      Tibet; 3) a large difference in HFMD transmission existed between northwest
      region and southeast region; 4) transmission characteristics determined incidence
      patterns: the higher the disease transmission in a province, the earlier the
      annual seasonality started and the more case percentage was among children 0-2
      years old and less among 3-5 years old. CONCLUSION: Because HFMD has higher
      transmission than most childhood infections reported, high effective vaccine
      coverage is needed to substantially reduce HFMD incidence. Control measures
      before the vaccine implementation should focus on 2-6 years old children in 30
      provinces and 10-14 years old children in Tibet.

PMID- 27871253
TI  - Impact of residual urine volume decline on the survival of chronic hemodialysis
      patients in Kinshasa.
AB  - BACKGROUND: Despite the multiple benefits of maintaining residual urine volume
      (RUV) in hemodialysis (HD), there is limited data from Sub-Saharan Africa. The
      aim of this study was to assess the impact of RUV decline on the survival of HD
      patients. METHODS: In a retrospective cohort study, 250 consecutive chronic HD
      patients (mean age 52.5 years; 68.8% male, median HD duration 6 months) from two
      hospitals in the city of Kinshasa were studied, between January 2007 and July
      2013. The primary outcome was lost RUV. Preserved or lost RUV was defined as
      decline RUV < 25 (median decline) or >= 25 ml/day/month, respectively. The second
      endpoint was survival (time-to death). Survival curves were built using the
      Kaplan-Meier methods. We used Log-rank test to compare survival curves.
      Predictors of mortality were assessed by Cox proportional hazards regression
      models. RESULTS: The cumulative incidence of patients with RUV decline was 52,
      4%. The median (IQR) decline in RUV was 25 (20.8-33.3) ml/day/month in the
      population studied, 56.7 (43.3-116.7) in patients deceased versus 12.9 (8.3-16.7)
      in survivor patients (p < 0.001). Overall mortality was 78 per 1000 patient years
      (17 per 1000 in preserved vs 61 per 1000 lost RUV). Forty six patients (18.4%)
      died from withdrawal of HD due to financial constraints. The Median survival was
      17 months in the whole group while, a significant difference was shown between
      lost (10 months, n = 119) vs preserved RUV group (30 months, n = 131; p = 0001).
      Multivariate Cox proportional hazards models showed that, decreased RUV (adjusted
      HR 5.35, 95% CI [2.73-10.51], p < 0.001), financial status (aHR 2.23, [1.11
      4.46], p = 0.024), hypervolemia (a HR 2.00, [1.17-3.40], p = 0.011), lacking ACEI
      (aHR 2.48, [1.40-4.40], p = 0.002) or beta blocker use (aHR 4.04, [1.42-11.54], p
      = 0.009), central venous catheter (aHR 6.26, [1.71-22.95], p = 0.006), serum
      albumin (aHR 0.93, [0.89-0.96], p < 0.001) and hemoglobin (aHR 0.73, [0.63-0.84],
      p < 0.001) had emerged as the independent predictors of all-cause mortality.
      CONCLUSION: More than half of HD patients in this cohort study experienced fast
      RUV decline which contributed substantially to increase mortality, highlighting
      the need for its prevention and management.

PMID- 27871255
TI  - Root resorption during orthodontic treatment with self-ligating or conventional
      brackets: a systematic review and meta-analysis.
AB  - BACKGROUND: The aim of this study was to compare the external apical root
      resorption (EARR) in patients receiving fixed orthodontic treatment with self
      ligating or conventional brackets. METHODS: Studies comparing the EARR between
      orthodontic patients using self-ligating or conventional brackets were identified
      through electronic search in databases including CENTRAL, PubMed, EMBASE, China
      National Knowledge Infrastructure (CNKI) and SIGLE, and manual search in relevant
      journals and reference lists of the included studies until Apr 2016. The
      extraction of data and risk of bias evaluation were conducted by two
      investigators independently. The original outcome underwent statistical pooling
      by using Review Manager 5. RESULTS: Seven studies were included in the systematic
      review, out of which, five studies were statistically pooled in meta-analysis.
      The value of EARR of maxillary central incisors in the self-ligating bracket
      group was significantly lower than that in the conventional bracket group (SMD 
      0.31; 95% CI: -0.60--0.01). No significant differences in other incisors were
      observed between self-ligating and conventional brackets. CONCLUSIONS: Current
      evidences suggest self-ligating brackets do not outperform conventional brackets
      in reducing the EARR in maxillary lateral incisors, mandible central incisors and
      mandible lateral incisors. However, self-ligating brackets appear to have an
      advantage in protecting maxillary central incisor from EARR, which still needs to
      be confirmed by more high-quality studies.

PMID- 27871254
TI  - Familial aggregation of albuminuria and arterial hypertension in an Aboriginal
      Australian community and the contribution of variants in ACE and TP53.
AB  - BACKGROUND: Aboriginal Australians are at high risk of cardiovascular, metabolic
      and renal diseases, resulting in a marked reduction in life expectancy when
      compared to the rest of the Australian population. This is partly due to
      recognized environmental and lifestyle risk factors, but a contribution of
      genetic susceptibility is also likely. METHODS: Using results from a
      comprehensive survey of one community (N = 1350 examined individuals), we have
      tested for familial aggregation of plasma glucose, arterial blood pressure,
      albuminuria (measured as urinary albumin to creatinine ratio, UACR) and estimated
      glomerular filtration rate (eGFR), and quantified the contribution of variation
      at four candidate genes (ACE; TP53; ENOS3; MTHFR). RESULTS: In the subsample of
      357 individuals with complete genotype and phenotype data we showed that both
      UACR (h2 = 64%) and blood pressure (sBP h2 = 29%, dBP, h2 = 11%) were
      significantly heritable. The ACE insertion-deletion (P = 0.0009) and TP53 codon72
      polymorphisms (P = 0.003) together contributed approximately 15% of the total
      heritability of UACR, with an effect of ACE genotype on BP also clearly evident.
      CONCLUSIONS: While the effects of the ACE insertion-deletion on risk of renal
      disease (especially in the setting of diabetes) are well recognized, this is only
      the second study to implicate p53 genotype as a risk factor for albuminuria - the
      other being an earlier study we performed in a different Aboriginal community
      (McDonald et al., J Am Soc Nephrol 13: 677-83, 2002). We conclude that there are
      significant genetic contributions to the high prevalence of chronic diseases
      observed in this population.

PMID- 27871256
TI  - Domestic violence among antenatal attendees in a Kathmandu hospital and its
      associated factors: a cross-sectional study.
AB  - BACKGROUND: Domestic violence during pregnancy is a public health problem which
      violates human rights and causes an adverse effect on both maternal and fetal
      health. The objectives of the study were to assess the prevalence of domestic
      violence among the pregnant women attending the antenatal clinic, to explore the
      associated factors, and to identify the perpetrators of domestic violence.
      METHODS: A descriptive cross-sectional study was conducted among 404 pregnant
      women in their third trimester of pregnancy. Convenient sampling was used to
      select the study population. Data collection tools consisted of questionnaires on
      socio-demographic characteristics of the woman and her spouse, social support,
      and the woman's attitude towards domestic violence, along with her experiences of
      psychological, physical, and sexual violence. Domestic violence was assessed
      using a questionnaire adapted from a World Health Organization multi-country
      study on women's health and life experiences. Relationships between domestic
      violence and the various factors were determined by bivariate analysis using a
      chi-square test. Binary logistic regression with 95% confidence interval and
      adjusted odds ratio were then applied to assess the factors independently
      associated with domestic violence. RESULTS: More than one-quarter (27.2%) of the
      pregnant women had experienced some form of violence. The most common form of
      violence was sexual violence (17.3%), followed by psychological violence (16.6%)
      and physical violence (3.2%). Husbands within the age group 25-34 years (AOR =
      0.38), women married for 2-5 years (AOR = 0.42) and who had one or two children
      (AOR = 0.32) were negatively associated with domestic violence. Whereas the
      presence of husband's controlling behavior (AOR = 1.88) and experience of
      violence before the current pregnancy (AOR = 24.55) increased the odds of
      experiencing violence during pregnancy. The husband was the major perpetrator in
      all type of violence. CONCLUSIONS: Domestic violence is common among pregnant
      women attending an antenatal clinic. It indicates a need for routine screening
      during antenatal visits to identify women experiencing violence and thus provide
      support services, thereby preventing them from adverse health consequences.

PMID- 27871257
TI  - Pregnancy related anxiety and general anxious or depressed mood and the choice
      for birth setting: a secondary data-analysis of the DELIVER study.
AB  - BACKGROUND: In several developed countries women with a low risk of complications
      during pregnancy and childbirth can make choices regarding place of birth. In the
      Netherlands, these women receive midwife-led care and can choose between a home
      or hospital birth. The declining rate of midwife-led home births alongside the
      recent debate on safety of home births in the Netherlands, however, suggest an
      association of choice of birth place with psychological factors related to safety
      and risk perception. In this study associations of pregnancy related anxiety and
      general anxious or depressed mood with (changes in) planned place of birth were
      explored in low risk women in midwife-led care until the start of labour.
      METHODS: Data (n = 2854 low risk women in midwife-led care at the onset of
      labour) were selected from the prospective multicenter DELIVER study. Women
      completed the Pregnancy Related Anxiety Questionnaire-Revised (PRAQ-R) to assess
      pregnancy related anxiety and the EuroQol-6D (EQ-6D) for an anxious and/or
      depressed mood. RESULTS: A high PRAQ-R score was associated with planned hospital
      birth in nulliparous (aOR 1.92; 95% CI 1.32-2.81) and parous women (aOR 2.08; 95%
      CI 1.55-2.80). An anxious or depressed mood was associated with planned hospital
      birth (aOR 1.58; 95% CI 1.20-2.08) and with being undecided (aOR 1.99; 95% CI
      1.23-2.99) in parous women only. The majority of women did not change their
      planned place of birth. Changing from an initially planned home birth to a
      hospital birth later in pregnancy was, however, associated with becoming anxious
      or depressed after 35 weeks gestation in nulliparous women (aOR 4.17; 95% CI 1.35
      12.89) and with pregnancy related anxiety at 20 weeks gestation in parous women
      (aOR 3.91; 95% CI 1.32-11.61). CONCLUSION: Low risk women who planned hospital
      birth (or who were undecided) more often reported pregnancy related anxiety or an
      anxious or depressed mood. Women who changed from home to hospital birth during
      pregnancy more often reported pregnancy related anxiety or an anxious or
      depressed mood in late pregnancy. Anxiety should be adequately addressed in the
      process of informed decision-making regarding planned place of birth in low risk
      women.

PMID- 27871258
TI  - Temporal profile of body temperature in acute ischemic stroke: relation to
      infarct size and outcome.
AB  - BACKGROUND: High body temperatures after ischemic stroke have been associated
      with larger infarct size, but the temporal profile of this relation is unknown.
      We assess the relation between temporal profile of body temperature and infarct
      size and functional outcome in patients with acute ischemic stroke. METHODS: In
      419 patients with acute ischemic stroke we assessed the relation between body
      temperature on admission and during the first 3 days with both infarct size and
      functional outcome. Infarct size was measured in milliliters on CT or MRI after 3
      days. Poor functional outcome was defined as a modified Rankin Scale score >=3 at
      3 months. RESULTS: Body temperature on admission was not associated with infarct
      size or poor outcome in adjusted analyses. By contrast, each additional 1.0 
      degrees C in body temperature on day 1 was associated with 0.31 ml larger infarct
      size (95% confidence interval (CI) 0.04-0.59), on day 2 with 1.13 ml larger
      infarct size(95% CI, 0.83-1.43), and on day 3 with 0.80 ml larger infarct size
      (95% CI, 0.48-1.12), in adjusted linear regression analyses. Higher peak body
      temperatures on days two and three were also associated with poor outcome
      (adjusted relative risks per additional 1.0  degrees C in body temperature, 1.52
      (95% CI, 1.17-1.99) and 1.47 (95% CI, 1.22-1.77), respectively). CONCLUSIONS:
      Higher peak body temperatures during the first days after ischemic stroke, rather
      than on admission, are associated with larger infarct size and poor functional
      outcome. This suggests that prevention of high temperatures may improve outcome
      if continued for at least 3 days.

PMID- 27871260
TI  - Are early first trimester weights valid proxies for preconception weight?
AB  - BACKGROUND: An accurate estimate of preconception weight is necessary for
      providing a gestational weight gain range based on the Institute of Medicine's
      guidelines; however, an accurate and proximal preconception weight is not
      available for most women. We examined the validity of first trimester weights for
      estimating preconception body mass index category. METHODS: Under identical
      measurement conditions, preconception weight and two first trimester weights
      (i.e., 4-10 and 12 weeks gestation) were obtained (n = 43). RESULTS: The 4-10
      week and the 12 week weight correctly classified 95 and 91% women, respectively.
      Mean weight changes were relatively small overall (M = 0.74 +/- 1.99 kg at 4-10
      weeks and M = 1.02 +/- 2.46 at 12 weeks). There was a significant difference in
      mean weight gain by body mass index category at 4-10 weeks (-0.09 +/- 1.86 kg for
      normal weight participants vs. 1.61 + 1.76 kg for overweight/obese participants,
      p = 0.01), but not at 12 weeks (0.53 +/- 2.29 kg for normal weight participants
      vs. 1.54 +/- 2.58 kg for overweight/obese participants). CONCLUSIONS: Assigning
      gestational weight gain guidelines based on an early first trimester weight
      resulted in 5-9% of women being misclassified depending on the gestational week
      the weight was obtained. Thus, most women are correctly classified based on a
      first trimester weight, particularly an early first trimester weight, although it
      is possible that modeling strategies could be developed to further improve
      estimates of preconception body mass index category. TRIAL REGISTRATION:
      Clinicaltrials.gov # NCT01131117 , registered May 25, 2010.

PMID- 27871259
TI  - Prevalence and determinants of diabetes among older adults in Ghana.
AB  - BACKGROUND: Diabetes is one of the leading non-communicable diseases in Africa,
      contributing to the increasing disease burden among the old adults. Thus, the aim
      of this study was to determine the prevalence and determinants of diabetes among
      adults aged 50 years and above in Ghana. METHODS: A cross sectional study based
      on data collected from Study of Ageing and Adult Health (SAGE) Wave 1 from 2007
      to 2008. Data was collected from 5565 respondents of whom 4135 were aged 50+
      years identified using a multistage stratified clusters design. Bivariate and
      hierarchical multivariable logistic regression models were used to examine the
      association of the determinants and diabetes. RESULTS: The weighted prevalence of
      diabetes among the adults aged 50 years and above in Ghana was 3.95% (95%
      Confidence Interval: 3.35-4.55) with the prevalence being insignificantly higher
      in females than males (2.16%, 95% CI: 1.69-2.76 vs. 1.73%, 95% CI: 1.28-2.33).
      Low level of physical activity (Adjusted Odds Ratio [AOR] 2.11, 95% CI: 1.21
      3.69) and obesity (AOR 4.81, 95% CI: 1.92-12.0) were associated with increased
      odds of diabetes among women while old age (AOR 2.58, 95% CI: 1.29-5.18) and
      university (AOR 12.8, 95% CI: 4.20-39.1), secondary (AOR 3.61, 95% CI: 1.38-9.47)
      and primary education (AOR 2.71, 95% CI: 1.02-7.19) were associated with
      increased the odds of diabetes among men. CONCLUSION: The prevalence of diabetes
      among old adults shows a similar trend with that of the general population.
      However, the prevalence may have been underestimated due to self-reporting and a
      high rate of undiagnosed diabetes. In addition, the determinants of diabetes
      among older adults are a clear indication of the need for diabetes prevention
      programme targeting the young people and that are gender specific to reduce the
      burden of diabetes at old age. Physical activity and nutrition should be
      emphasised in any prevention strategy.

PMID- 27871261
TI  - Quantitative characterization of T-cell repertoire and biomarkers in kidney
      transplant rejection.
AB  - BACKGROUND: T-cell-mediated rejection (TCMR) remains a major cause of kidney
      allograft failure. The characterization of T-cell repertoire in different
      immunological disorders has emerged recently as a novel tool with significant
      implications. We herein sought to characterize T-cell repertoire using next
      generation sequencing to diagnose TCMR. METHODS: In this prospective study, we
      analyzed samples from 50 kidney transplant recipients. We collected blood and
      kidney transplant biopsy samples at sequential time points before and post
      transplant. We used next generation sequencing to characterize T-cell receptor
      (TCR) repertoire by using illumina miSeq on cDNA synthesized from RNA extracted
      from six patients' samples. We also measured RNA expression levels of FOXP3, CD8,
      CD4, granzyme and perforin in blood samples from all 50 patients. RESULTS: Seven
      patients developed TCMR during the first three months of the study. Out of six
      patients who had complete sets of blood and biopsy samples two had TCMR. We found
      an expansion of the TCR repertoire in blood at time of rejection when compared to
      that at pre-transplant or one-month post transplant. Patients with TCMR (n = 7)
      had significantly higher RNA expression levels of FOXP3, Perforin, Granzyme, CD4
      and CD8 in blood samples than those with no TCMR (n = 43) (P = 0.02, P = 0.003, P
      = 0.002, P = 0.017, and P = 0.01, respectively). CONCLUSIONS: Our study provides
      a potential utilization of TCR clone kinetics analysis in the diagnosis of TCMR.
      This approach may allow for the identification of the expanded T-cell clones
      associated with the rejection and lead to potential noninvasive diagnosis and
      targeted therapies of TCMR.

PMID- 27871262
TI  - Determinants of seasonal influenza vaccination in pregnant women in Valencia,
      Spain.
AB  - BACKGROUND: In most countries the coverage of seasonal influenza vaccination in
      pregnant women is low. We investigated the acceptance, reasons for rejection and
      professional involvement related to vaccine information in pregnant women in
      Valencia, Spain. METHODS: Observational retrospective study in 200 pregnant
      women, 100 vaccinated and 100 unvaccinated, were interviewed during the 2014/2015
      vaccination campaign. Electronic medical records, immunization registry and
      telephone interviews were used to determine reasons for vaccination and
      immunization rejection. RESULTS: 40.5% of pregnant women in the health department
      were vaccinated. The midwife was identified as source of information for 89% of
      women. The vaccine was rejected due to low perceptions of risk of influenza
      infection (23%), lack of information (19%), considering the vaccine as
      superfluous (16%), close proximity of delivery date (13%) and fear of side
      effects (12%). CONCLUSION: Pregnant women in Spain declined to be vaccinated due
      to under-estimation of the risk of contracting or being harmed by influenza, and
      lack of information. Interventions aiming to optimize vaccination coverage should
      include information addressing the safety and effectiveness of the current
      vaccine together with improved professional training and motivation.

PMID- 27871263
TI  - Perceived needs and health-related quality of life in people with schizophrenia
      and metabolic syndrome: a "real-world" study.
AB  - BACKGROUND: The complexity of schizophrenia lies in the combination of
      psychiatric, somatic and social needs requiring care. The aim of the study was to
      compare perceived needs between groups with absence/presence of metabolic
      syndrome (MetS) and to analyze the relationship between needs, health-related
      quality of life (HRQoL) and MetS in people with schizophrenia or schizoaffective
      disorder. METHODS: A "real-world" cross-sectional study was set up with a
      comprehensive framework including the following, needs for care (Camberwell
      Assessment of Need Interview [CAN]), HRQoL (Euro Qol-5D Questionnaire),
      sociodemographic data, lifestyle habits, psychopathology (Positive And Negative
      Syndrome Scale [PANSS]), global functioning (Global Assessment of Functioning
      Scale [GAF]), anthropometric measurements and blood test results were assessed
      for an outpatient sample (n = 60). RESULTS: The mean number of needs (given by
      CAN) was identified for both groups. Patients with MetS rated a higher number of
      needs compared to the group without this condition. Mobility problems (given by
      EQ-5D) were negatively associated with the number of total and unmet needs. For
      participants with MetS, HRQoL was related to the number of needs and unmet needs.
      For people with MetS, positive symptomatology score (given by PANSS) was related
      to the number of needs and met needs and general symptomatology was associated
      with total, met and unmet needs. For individuals without MetS, the global
      functioning score (given by GAF) was significantly inversely related with total,
      met and unmet needs. CONCLUSIONS: Needs and HRQoL, as well as general
      symptomatology, were related only in patients with MetS. This has implications
      for treatment planning at the individual and organizational levels. An analysis
      of both physical and mental needs could provide a starting point for the
      extension of facilities in the health care system in order to reach the goal of
      improving quality of life.

PMID- 27871264
TI  - STI tests and proportion of positive tests in female sex workers attending local
      public health departments in Germany in 2010/11.
AB  - BACKGROUND: In Germany, local public health departments (LPHD) are required to
      offer low-threshold access to confidential counselling and testing for sexually
      transmitted infections (STI) for sex workers. We collected data from LPHD in
      Germany to estimate the number of performed STI tests and the proportion of
      positive STI tests among attending female sex workers (FSW) in order to formulate
      recommendations for improving STI testing and care for FSW in Germany. METHODS:
      We recruited LPHD across Germany to collect aggregated data on attending FSW
      between January 2010 and March 2011. Baseline characteristics, the number of
      attending FSW, STI tests (HIV, Chlamydia trachomatis, Neisseria gonorrhoea,
      syphilis and Trichomonas vaginalis) and the number of positive results were
      provided by participating LPHD. We described the number of STI tests per FSW
      visit and the proportion of positive test results, including interquartile range
      (IQR). We tested whether baseline characteristics of LPHD were associated with
      the proportion of positive test results. RESULTS: Overall, 28 LPHD from 14 of the
      16 federal states reported 9284 FSW visits over the study period, with a median
      of 188 FSW visits (IQR 45-440) per LPHD. Overall, a median of 77.1% (IQR 60.7
      88.0) of visiting FSW received a test for Neisseria gonorrhoea, followed by HIV
      (66.0%, IQR 47.9-86.8), Chlamydia trachomatis (65.4%, IQR 50.7-83.6) and syphilis
      (61.6, IQR 48.6-78.6). In total, 22,914 STI tests were performed. The proportion
      of positive tests was 3.1% (IQR 1.3-4.8), with the highest proportion of positive
      tests for Chlamydia trachomatis (6.8%, IQR 2.5-10.4), followed by Neisseria
      gonorrhoea (3.2%, IQR 0.0-5.3), Trichomonas vaginalis (3.0%, IQR 0.0-15.4),
      syphilis (1.1%, IQR 0.0-1.3) and HIV (0.2%, IQR 0.0-0.4). The proportion of
      positive tests varied between 0 and 13.9% between LPHD, with a higher variation
      of proportion of positive tests in LPHD with a smaller number of reported STI
      tests. CONCLUSIONS: Participating LPHD varied in terms of performed STI tests and
      FSW visits. The proportion of positive STI tests was low, but varied between
      LPHD. This variation likely reflects different testing strategies. Existing
      testing guidelines should be used by all LPHD to ensure high quality care for
      FSW.

PMID- 27871265
TI  - The association between different opioid doses and the survival of advanced
      cancer patients receiving palliative care.
AB  - BACKGROUND: Concerns that opioids may hasten death can be a cause of the
      physicians' reluctance to prescribe opioids, leading to inadequate symptom
      palliation. Our aim was to find if there was an association between different
      opioid doses and the survival of the cancer patients that participated in our
      palliative care program. METHODS: A retrospective study was conducted at
      Ramathibodi Hospital, Bangkok between January 2013 and December 2015. All of the
      cancer patients that were referred to palliative care teams by their primary
      physicians were included in the study. The study data included the patients'
      demographics, disease status, comorbidities, functional status, type of services,
      cancer treatments, date of consultation, and the date of the patient's death or
      last follow-up. The information concerning opioid use was collected by reviewing
      the medical records and this was converted to an oral morphine equivalent (OME),
      following a standard ratio. The time-varying covariate in the Cox regression
      analysis was applied in order to determine the association between different
      doses of opioids and patient survival. RESULTS: A total of 317 cancer patients
      were included in the study. The median (IQR) of the OME among our patients was
      6.43 mg/day (0.53, 27.36). The univariate Cox regression analysis did not show
      any association between different opioid doses (OME <= 30 mg/day and > 30 mg/day)
      and the patients' survival (p = 0.52). The PPS levels (p < 0.01), palliative care
      clinic visits (HR 0.32, 95%CI 0.24-0.43), home visits (HR 0.75, 95%CI 0.57-0.99),
      chemotherapy (HR 0.32, 95%CI 0.22-0.46), and radiotherapy (HR 0.53, 95%CI 0.36
      0.78) were identified as factors that increased the probability of survival.
      CONCLUSIONS: Our study has demonstrated that different opioid doses in advanced
      cancer patients are not associated with shortened survival period.

PMID- 27871266
TI  - Antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of organic
      and aqueous extracts of Hopea odorata leaves and in silico PASS prediction of its
      isolated compounds.
AB  - BACKGROUND: Hopea Odorata, locally known as Telsur (Bangladesh), has some
      traditional uses as folk medicine. This study aims to investigate the
      antioxidant, antidiarrheal, hypoglycemic and thrombolytic activities of H.
      odorata leaf extracts as new therapeutic prospects predicting the activity of
      some of the isolated compounds of this plant. METHODS: Leaves of Hopea odorata
      was extracted with pure methanol (MEHO), ethanol (EEHO) and water (AEHO). The
      extract was tested for antioxidant activity by using reducing power and H2O2
      scavenging assay. Antidiarrheal effects were assayed by three standard methods of
      bioassay: Castor oil-induced diarrhea, Castor oil induced enteropooling and
      gastrointestinal transit test. Hypoglycemic effect was determined by
      normoglycemic model of mice. Thrombolytic activity was evaluated by clot lyses
      test for human and mice blood. In silico PASS prediction was applied for
      phytoconstituents namely Balanocarpol, Hopeaphenol and Ampelopsin H isolated from
      this plant. RESULT: Among the all extracts, MEHO exhibited strong antioxidant
      activity in both reducing power and H2O2 scavenging assay. Phenol content of MEHO
      was 297.22 +/- 0.78 mg/g and flavonol content was 91.53 +/- 1.82 mg/g. All the
      experiment of extracts at dose of 200 and 400 mg/kg and the standard drug
      loperamide (5 mg/kg) showed significant (p < 0.001) inhibition against castor oil
      induced diarrhea and castor oil induced enteropooling in mice. There were also
      significant (p < 0.01) reduction in gastrointestinal motility in the charcoal
      meal test. Leaf extract showed no significant (P < 0.01) decrease of blood
      glucose compared to Glibenclamide in normoglycemic mice. Using an in vitro
      thrombolytic model, MEHO showed the highest and significant clot lysis of human
      and mice blood compared to Streptokinase. PASS predicted the wide range of
      antioxidant, free radical scavenger, Nitric oxide scavenger, cardioprotectant,
      hepatoprotectant, thrombolytic, fibrinolytic, antibacterial, antifungal,
      anticarcinogenic, anthelmintic and anti-inflammatory activity of examined
      phytoconstituents. CONCLUSION: These findings suggest that the plant may be a
      potential source of new antidiarrheal, thrombolytic and antioxidative agents but
      it is found to have no antidiabetic capability. PASS prediction matched with
      present study for the extracts. Further study needs to identify the PASS
      predicted biological actions of the phytoconstituents.

PMID- 27871267
TI  - Sedentary lifestyle and its associated factors among adolescents from public and
      private schools of a Brazilian state capital.
AB  - BACKGROUND: Adolescence is a transition stage between childhood and adulthood and
      is an important phase for the acquisition of future lifestyles, including the
      practice of physical activity (PA). The prevalence of sedentary lifestyle in
      adolescents is often high, creating the need for studies addressing the practice
      of PA and its associated factors for a better understanding of the phenomenon and
      possible interventions that would encourage positive changes. METHODS: Cross
      sectional study of a representative sample of students aged 14-18 years enrolled
      in both public and private schools of a large Brazilian city to determine the
      level of physical activity (PA) and its associated factors. Sedentary lifestyle
      was measured by applying the International Physical Activity Questionnaire. The
      independent variables were gender, age, race, tobacco use and alcohol consumption
      in the past 30 days, socioeconomic status, body mass index, waist circumference
      and blood pressure. The crude prevalence ratio was used as a measure of
      association and was estimated from a Poisson regression. RESULTS: The sample
      consisted of 862 adolescents with a mean age of 15.4 +/- 1.1 years. Females were
      predominant (52.8%), and the age between 14 and 15 years was the most frequent
      (52.2%). The majority of the group reported themselves as Caucasians (51.2%),
      belonging to socioeconomic class C (52.5%) and were attending to public schools
      (69.1%). The prevalence of sedentary lifestyle was 66.8% (95% confidence interval
      [CI]: 63.5-69.9), where values of 65.4% and 69.9% were observed among students
      from public and private schools, respectively (p = 0.196). Sedentary lifestyle
      was more frequent in females (78.0% vs 54.3%; p < 0.001). The factor directly
      associated with sedentary lifestyle was female gender both in public and private
      schools and the only independent variable related to sedentarism was also female
      gender. CONCLUSION: The prevalence of sedentary lifestyle was extremely high in
      the population of adolescents studied both in public and private schools. Female
      sex was directly associated with sedentary lifestyle.

PMID- 27871268
TI  - Metformin and dietary advice to improve insulin sensitivity and promote
      gestational restriction of weight among pregnant women who are overweight or
      obese: the GRoW Randomised Trial.
AB  - BACKGROUND: Obesity is a significant global health problem, with approximately
      50% of women entering pregnancy having a body mass index greater than or equal to
      25 kg/m2. Obesity during pregnancy is associated with a well-recognised increased
      risk of adverse health outcomes both for the woman and her infant. Currently
      available data from large scale randomised trials and systematic reviews
      highlight only modest effects of antenatal dietary and lifestyle interventions in
      limiting gestational weight gain, with little impact on clinically relevant
      pregnancy outcomes. Further information evaluating alternative strategies is
      required. The aims of this randomised controlled trial are to assess whether the
      use of metformin as an adjunct therapy to dietary and lifestyle advice for
      overweight and obese women during pregnancy is effective in improving maternal,
      fetal and infant health outcomes. METHODS: Design: Multicentre randomised,
      controlled trial. INCLUSION CRITERIA: Women with a singleton, live gestation
      between 10+0-20+0 weeks who are obese or overweight (defined as body mass index
      greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry &
      Randomisation: Eligible, consenting women will be randomised between 10+0 and
      20+0 weeks gestation using an online computer randomisation system, and
      randomisation schedule prepared by non-clinical research staff with balanced
      variable blocks. Stratification will be according to maternal BMI at trial entry,
      parity, and centre where planned to give birth. Treatment Schedules: Women
      randomised to the Metformin Group will receive a supply of 500 mg oral metformin
      tablets. Women randomised to the Placebo Group will receive a supply of identical
      appearing and tasting placebo tablets. Women will be instructed to commence
      taking one tablet daily for a period of one week, increasing to a maximum of two
      tablets twice daily over four weeks and then continuing until birth. Women,
      clinicians, researchers and outcome assessors will be blinded to the allocated
      treatment group. All women will receive three face-to-face sessions (two with a
      research dietitian and one with a trained research assistant), and three
      telephone calls over the course of their pregnancy, in which they will be
      provided with dietary and lifestyle advice, and encouraged to make change
      utilising a SMART goals approach. Primary Study Outcome: infant birth weight
      >4000 grams. SAMPLE SIZE: 524 women to detect a difference from 15.5% to 7.35%
      reduction in infants with birth weight >4000 grams (p = 0.05, 80% power, two
      tailed). DISCUSSION: This is a protocol for a randomised trial. The findings will
      contribute to the development of evidence based clinical practice guidelines.
      TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12612001277831 , prospectively registered 10th of December, 2012.

PMID- 27871269
TI  - Institutionalizing postpartum intrauterine device (IUD) services in Sri Lanka,
      Tanzania, and Nepal: study protocol for a cluster-randomized stepped-wedge trial.
AB  - BACKGROUND: During the year following the birth of a child, 40% of women are
      estimated to have an unmet need for contraception. The copper IUD provides safe,
      effective, convenient, and long-term contraceptive protection that does not
      interfere with breastfeeding during the postpartum period. Postpartum IUD (PPIUD)
      insertion should be performed by a trained provider in the early postpartum
      period to reduce expulsion rates and complications, but these services are not
      widely available. The International Federation of Obstetricians and Gynecologists
      (FIGO) will implement an intervention that aims to institutionalize PPIUD
      training as a regular part of the OB/GYN training program and to integrate it as
      part of the standard practice at the time of delivery in intervention hospitals.
      METHODS: This trial uses a cluster-randomized stepped wedge design to assess the
      causal effect of the FIGO intervention on the uptake and continued use of PPIUD
      and of the effect on subsequent pregnancy and birth. This trial also seeks to
      measure institutionalization of PPIUD services in study hospitals and diffusion
      of these services to other providers and health facilities. This study will also
      include a nested mixed-methods performance evaluation to describe intervention
      implementation. DISCUSSION: This study will provide critical evidence on the
      causal effects of hospital-based PPIUD provision on contraceptive choices and
      reproductive health outcomes, as well as on the feasibility, acceptability and
      longer run institutional impacts in three low- and middle-income countries. TRIAL
      REGISTRATION: Trial registered on March 11, 2016 with ClinicalTrials.gov,
      NCT02718222 .

PMID- 27871270
TI  - Might radiation therapy in addition to chemotherapy improve overall survival of
      patients with non-oligometastatic Stage IV non-small cell lung cancer?: Secondary
      analysis of two prospective studies.
AB  - BACKGROUND: The role of radiation therapy in addition to chemotherapy has not
      been well established in non-oligometastatic Stage IV non-small cell lung cancer
      (NSCLC). We aimed to investigate overall survival (OS) of non-oligometastatic
      Stage IV NSCLC treated with chemotherapy with concurrent radiation to the primary
      tumor. METHODS: Eligible patients were screened from two prospective studies.
      Oligometastatic and non-oligometastatic NSCLC were defined as having < 5 and >=5
      metastatic lesions, respectively. Prognostic factors for OS were identified by
      using univariate and multivariate analysis. Landmark analysis and propensity
      score matching (PSM) were each performed to further adjust for confounding.
      RESULTS: A total of 274 patients were identified as the study cohort: 183 had non
      oligometastatic disease. For all 274 patients, those who received a radiation
      dose >=63 Gy to the primary tumor and had oligometastatic disease had better OS
      (P < 0.001 and P = 0.017, respectively). When patients were subdivided into those
      with oligometastatic or non-oligometastatic disease, a radiation dose >= 63 Gy
      remained a significant prognostic factor for better OS. For non-oligometastatic
      patients, multivariate analysis showed that receiving >=63 Gy radiation, having a
      GTV <146 cm3, having response to chemotherapy, and having stable or increased
      post-treatment KPS independently predicted better OS (P = 0.018, P = 0.014, P =
      0.014, and P = 0.001). After PSM in non-oligometastatic patients, a higher
      radiation dose (>=63 Gy) remained to be correlated with better OS. By landmark
      analysis, aggressive radiation (>=63 Gy) remained to be correlated with better OS
      in Pre-PSM cohort (P = 0.005) and Post-PSM cohort (P = 0.004). CONCLUSIONS:
      Radiation dose, primary tumor volume, response to chemotherapy and KPS after
      treatment are associated with OS in patients with non-oligometastatic disease; on
      basis of effective system chemotherapy, aggressive thoracic radiotherapy may
      prolong OS.

PMID- 27871271
TI  - Assessing the acceptability and feasibility of encounter decision aids for early
      stage breast cancer targeted at underserved patients.
AB  - BACKGROUND: Women of low socioeconomic status (SES) diagnosed with early stage
      breast cancer are less likely to be involved in treatment decisions. They tend to
      report higher decisional regret and poorer communication. Evidence suggests that
      well-designed encounter decision aids (DAs) could improve outcomes and
      potentially reduce healthcare disparities. Our goal was to evaluate the
      acceptability and feasibility of encounter decision aids (Option Grid, Comic
      Option Grid, and Picture Option Grid) adapted for a low-SES and low-literacy
      population. METHODS: We used a multi-phase, mixed-methods approach. In phase 1,
      we conducted a focus group with rural community stakeholders. In phase 2, we
      developed and administered a web-based questionnaire with patients of low and
      high SES. In phase 3, we interviewed patients of low SES and relevant healthcare
      professionals. RESULTS: Data from phase 1 (n = 5) highlighted the importance of
      addressing treatment costs for patients. Data from phase 2 (n = 268) and phase 3
      (n = 15) indicated that using both visual displays and numbers are helpful for
      understanding statistical information. Data from all three phases suggested that
      using plain language and simple images (Picture Option Grid) was most acceptable
      and feasible. The Comic Option Grid was deemed least acceptable. CONCLUSION:
      Option Grid and Picture Option Grid appeared acceptable and feasible in
      facilitating patient involvement and improving perceived understanding among
      patients of high and low SES. Picture Option Grid was considered most acceptable,
      accessible and feasible in the clinic visit. However, given the small sample
      sizes used, those findings need to be interpreted with caution. Further research
      is needed to determine the impact of pictorial and text-based encounter decision
      aids in underserved patients and across socioeconomic strata.

PMID- 27871273
TI  - The impact of body vigilance on help-seeking for cancer 'alarm' symptoms: a
      community-based survey.
AB  - BACKGROUND: The act of detecting bodily changes is a pre-requisite for subsequent
      responses to symptoms, such as seeking medical help. This is the first study to
      explore associations between self-reported body vigilance and help-seeking in a
      community sample currently experiencing cancer 'alarm' symptoms. METHODS: Using a
      cross-sectional study design, a 'health survey' was mailed through primary care
      practices to 4913 UK adults (age >=50 years, no cancer diagnosis), asking about
      symptom experiences and medical help-seeking over the previous three months. Body
      vigilance, cancer worry and current illness were assessed with a small number of
      self-report items derived from existing measures. RESULTS: The response rate was
      42% (N = 2042). Almost half the respondents (936/2042; 46%) experienced at least
      one cancer alarm symptom. Results from logistic regression analysis revealed that
      paying more attention to bodily changes was significantly associated with help
      seeking for cancer symptoms (OR = 1.44; 1.06-1.97), after controlling for socio
      demographics, current illness and cancer worry. Being more sensitive to bodily
      changes was not significantly associated with help-seeking. CONCLUSIONS:
      Respondents who paid attention to their bodily changes were more likely to seek
      help for their symptoms. Although the use of a cross-sectional study design and
      the limited assessment of key variables preclude any firm conclusions,
      encouraging people to be body vigilant may contribute towards earlier cancer
      diagnosis. More needs to be understood about the impact this might have on cancer
      related anxiety.

PMID- 27871272
TI  - Association of tryptophan hydroxylase-2 polymorphisms with oppositional defiant
      disorder in a Chinese Han population.
AB  - BACKGROUND: Oppositional defiant disorder (ODD) is a behavioral disorder of
      school-age population. It is well known that 5-HT dysfunction is correlated with
      impulsivity, which is one of the common characteristics of ODD. The enzyme
      tryptophan hydroxylase-2 (TPH-2) synthesizes 5-HT in serotonergic neurons of the
      midbrain raphe. The purposes of this study were to investigate the potential
      association of TPH-2 polymorphisms with susceptibility to ODD in a Han Chinese
      school population. METHODS: Four polymorphisms (rs4570625, rs11178997, rs1386494
      and rs7305115) of the TPH-2 gene were analyzed by using polymerase chain reaction
      and DNA microarray hybridization in a case-control study of 276 Han Chinese
      individuals (124 ODD and 152 controls). RESULTS: In single marker analyses,there
      was a significant difference in the genotype (chi 2  = 4.163, P = 0.041) and
      allele frequency (chi 2  = 3.930, P = 0.047) of rs1386494 between ODD and control
      groups. Haplotype analyses revealed higher frequencies of haplotypes TA
      (rs4570625-rs11178997), TAG (rs4570625-rs11178997-rs1386494), TAA (rs4570625
      rs11178997-rs7305115) and TAGA (rs4570625-rs11178997-rs1386494-rs7305115), but
      lower frequencies of haplotypes GA (rs4570625-rs11178997) and GAG (rs4570625
      rs11178997-rs1386494) in ODD compared to control groups. CONCLUSIONS: These
      findings suggest the role of these TPH-2 gene variants in susceptibility to ODD.
      Some haplotypes might be the risk factors for Chinese Han children with ODD,
      while others might be preventable factors.

PMID- 27871275
TI  - Rationale and design of SuPPoRT: a multi-centre randomised controlled trial to
      compare three treatments: cervical cerclage, cervical pessary and vaginal
      progesterone, for the prevention of preterm birth in women who develop a short
      cervix.
AB  - BACKGROUND: Clinically, once a woman has been identified as being at risk of
      spontaneous preterm birth (sPTB) due to a short cervical length, a decision
      regarding prophylactic treatment must be made. Three interventions have the
      potential to improve outcomes: cervical cerclage (stitch), vaginal progesterone
      and cervical pessary. Each has been shown to have similar benefit in reduction of
      sPTB, but there have been no randomised control trials (RCTs) to compare them.
      METHODS: This open label multi-centre UK RCT trial, will evaluate whether the
      three interventions are equally efficacious to prevent premature birth in women
      who develop a short cervix (<25 mm on transvaginal ultrasound). Participants will
      be asymptomatic and between 14+0 and 23+6 weeks' gestation in singleton
      pregnancies. Eligible women will be randomised to cervical cerclage, Arabin
      pessary or vaginal progesterone (200 mg once daily) (n = 170 women per group).
      The obstetric endpoints are premature birth rate <37 weeks' of gestation
      (primary), 34 weeks and 30 weeks (secondary outcomes) and short-term neonatal
      outcomes (a composite of death and major morbidity). It will also explore whether
      intervention success can be predicted by pre-intervention biomarker status.
      DISCUSSION: Preterm birth is the leading cause of perinatal morbidity and
      mortality and a short cervix is a useful way of identifying those most at risk.
      However, best management of these women has presented a clinical conundrum for
      decades. Given the promise offered by cerclage, Arabin pessary and vaginal
      progesterone for prevention of preterm birth in individual trials, direct
      comparison of these prophylactic interventions is now essential to establish
      whether one treatment is superior. If, as we hypothesise, the three interventions
      are equally efficacious, this study will empower women to make a choice of
      treatments based on personal preference and quality of life issues also explored
      by the study. Our exploratory analysis into whether the response to intervention
      is related to the pre-intervention biomarker status further our understanding of
      the pathophysiology of spontaneous preterm birth and help focus future research
      questions. TRIAL REGISTRATION: EudraCT Number: 2015-000456-15 . Registered 11th
      March 2015.

PMID- 27871274
TI  - Chemotherapy curable malignancies and cancer stem cells: a biological review and
      hypothesis.
AB  - BACKGROUND: Cytotoxic chemotherapy brings routine cures to only a small select
      group of metastatic malignancies comprising gestational trophoblast tumours, germ
      cell tumours, acute leukemia, Hodgkin's disease, high grade lymphomas and some of
      the rare childhood malignancies. We have previously postulated that the extreme
      sensitivity to chemotherapy for these malignancies is linked to the on-going high
      levels of apoptotic sensitivity that is naturally linked with the unique genetic
      events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and
      gastrulation that have occurred within the cells of origin of these malignancies.
      In this review we will examine the cancer stem cell/cancer cell relationship of
      each of the chemotherapy curable malignancies and how this relationship impacts
      on the resultant biology and pro-apoptotic sensitivity of the varying cancer cell
      types. DISCUSSION: In contrast to the common epithelial cancers, in each of the
      chemotherapy curable malignancies there are no conventional hierarchical cancer
      stem cells. However cells with cancer stem like qualities can arise
      stochastically from within the general tumour cell population. These stochastic
      stem cells acquire a degree of resistance to DNA damaging agents but also retain
      much of the key characteristics of the cancer cells from which they develop. We
      would argue that the balance between the acquired resistance of the stochastic
      cancer stem cell and the inherent chemotherapy sensitivity of parent tumour cell
      determines the overall chemotherapy curability of each diagnosis. The cancer stem
      cells in the chemotherapy curable malignancies appear to have two key biological
      differences from those of the more common chemotherapy incurable malignancies.
      The first difference is that the conventional hierarchical pattern of cancer stem
      cells is absent in each of the chemotherapy curable malignancies. The other key
      difference, we suggest, is that the stochastic stem cells in the chemotherapy
      curable malignancies take on a significant aspect of the biological
      characteristics of their parent cancer cells. This action includes for the
      chemotherapy curable malignancies the heightened pro-apoptotic sensitivity linked
      to their respective associated unique genetic events. For the chemotherapy
      curable malignancies the combination of the relationship of their cancer stem
      cells combined with the extreme inherent sensitivity to induction of apoptosis
      from DNA damaging agents plays a key role in determining their overall curability
      with chemotherapy.

PMID- 27871276
TI  - The future of global health education: training for equity in global health.
AB  - BACKGROUND: Among academic institutions in the United States, interest in global
      health has grown substantially: by the number of students seeking global health
      opportunities at all stages of training, and by the increase in institutional
      partnerships and newly established centers, institutes, and initiatives to house
      global health programs at undergraduate, public health and medical schools.
      Witnessing this remarkable growth should compel health educators to question
      whether the training and guidance that we provide to students today is
      appropriate, and whether it will be applicable in the next decade and beyond.
      Given that "global health" did not exist as an academic discipline in the United
      States 20 years ago, what can we expect it will look like 20 years from now and
      how can we prepare for that future? DISCUSSION: Most clinicians and trainees
      today recognize the importance of true partnership and capacity building in both
      directions for successful international collaborations. The challenge is in the
      execution of these practices. There are projects around the world where this is
      occurring and equitable partnerships have been established. Based on our
      experience and observations of the current landscape of academic global health,
      we share a perspective on principles of engagement, highlighting instances where
      partnerships have thrived, and examples of where we, as a global community, have
      fallen short. CONCLUSIONS: As the world moves beyond the charity model of global
      health (and its colonial roots), it is evident that the issue underlying ethical
      global health practice is partnership and the pursuit of health equity. Thus,
      achieving equity in global health education and practice ought to be central to
      our mission as educators and advisors when preparing trainees for careers in this
      field. Seeking to eliminate health inequities wherever they are ingrained will
      reveal the injustices around the globe and in our own cities and towns.

PMID- 27871277
TI  - Pulmonary endothelial activation caused by extracellular histones contributes to
      neutrophil activation in acute respiratory distress syndrome.
AB  - BACKGROUND: During the acute respiratory distress syndrome (ARDS), neutrophils
      play a central role in the pathogenesis, and their activation requires
      interaction with the endothelium. Extracellular histones have been recognized as
      pivotal inflammatory mediators. This study was to investigate the role of
      pulmonary endothelial activation during the extracellular histone-induced
      inflammatory response in ARDS. METHODS: ARDS was induced in male C57BL/6 mice by
      intravenous injection with lipopolysaccharide (LPS) or exogenous histones.
      Concurrent with LPS administration, anti-histone H4 antibody (anti-H4) or non
      specific IgG was administered to study the role of extracellular histones. The
      circulating von Willebrand factor (vWF) and soluble thrombomodulin (sTM) were
      measured with ELISA kits at the preset time points. Myeloperoxidase (MPO)
      activity in lung tissue was measured with a MPO detection kit. The translocation
      of P-selectin and neutrophil infiltration were measured by immunohistochemical
      detection. For in vitro studies, histone H4 in the supernatant of mouse lung
      vascular endothelial cells (MLVECs) was measured by Western blot. The binding of
      extracellular histones with endothelial membrane was examined by confocal laser
      microscopy. Endothelial P-selectin translocation was measured by cell surface
      ELISA. Adhesion of neutrophils to MLVECs was assessed with a color video digital
      camera. RESULTS: The results showed that during LPS-induced ARDS extracellular
      histones caused endothelial and neutrophil activation, as seen by P-selectin
      translocation, release of vWF, an increase of circulating sTM, lung neutrophil
      infiltration and increased MPO activity. Extracellular histones directly bound
      and activated MLVECs in a dose-dependent manner. On the contrary, the direct
      stimulatory effect of exogenous histones on neutrophils was very limited, as
      measured by neutrophil adhesion and MPO activity. With the contribution of
      activated endothelium, extracellular histones could effectively activating
      neutrophils. Both inhibiting the endothelial activation with an anti-toll like
      receptor (TLR) antibody and inhibiting the interaction of the endothelium with
      neutrophil using an anti-P-selectin antibody decreased the degree of neutrophil
      activation. CONCLUSIONS: Extracellular histones are pro-inflammatory mediators in
      LPS-induced ARDS in mice. In addition to direct action to neutrophils,
      extracellular histones promote neutrophil adhesion and subsequent activation by
      first activating the pulmonary endothelium via TLR signaling. Thus, endothelial
      activation is important for extracellular histone-induced inflammatory injury.

PMID- 27871278
TI  - The prognostic significance of human epidermal growth factor receptor family
      protein expression in operable pancreatic cancer : HER1-4 protein expression and
      prognosis in pancreatic cancer.
AB  - BACKGROUND: Prognostic factors aid in the stratification and treatment of cancer.
      This study evaluated the prognostic significance of human epidermal growth factor
      receptor (HER) family members (HER1-4) expression in patients with operable
      pancreatic cancer. METHODS: The expression of individual HER proteins in patient
      tissue specimens was detected by immunohistochemistry staining. Patient follow-up
      time was between 1.0 and 78.1 months. RESULTS: Positive expression of HER1, HER2,
      HER3 and HER4 was detected in 41.4, 60.0, 24.3 and 65.7% of cases, respectively.
      Kaplan-Meier analysis revealed that HER3 positive expression was associated with
      decreased median survival time (12.0 vs. 25.6 months for HER3 positive and
      negative groups, respectively; P = 0.013). Cox's regression confirmed that
      positive HER3 expression was an independent predictor of poor survival (RR =
      3.684, P = 0.001). In contrast, HER4 negative patients had a significantly
      decreased median survival time when compared with HER4 positive patients (11.4
      vs. 25.6 months, respectively; P = 0.027). However, HER4 was not an independent
      predictor of survival. No significant association between HER1 or HER2 expression
      and survival was observed (P = 0.626 & P = 0.859, respectively). CONCLUSIONS:
      HER3 is an independent prognostic marker for patients with operable pancreatic
      cancer. HER4 may also be of potential prognostic value in this disease and
      deserves further attention.

PMID- 27871279
TI  - Biodegradation of lignin and nicotine with white rot fungi for the
      delignification and detoxification of tobacco stalk.
AB  - BACKGROUND: Tobacco stalk is one kind of abundant crop residues in China. The
      high lignification of tobacco stalk increases its reusing cost and the existing
      of nicotine will cause serious pollution. The biodegradation of lignocellulosic
      biomass has been demonstrated to be an environmental and economical approach for
      the utilization of plant stalk. Meanwhile, many nicotine-degrading microorganisms
      were found in nature. However, microorganisms which could degraded both nicotine
      and lignin haven't been reported. Therefore, it's imperative to find some
      suitable microorganisms to break down lignin and simultaneously remove nicotine
      in tobacco stalk. RESULTS: The nicotine in tobacco stalk could be degraded
      effectively by Trametes versicolor, Trametes hirsute and Phanerochaete
      chrysosporium. The nicotine content in tobacco stalk was lowered to below 500
      mg/kg (a safe concentration to environment) after 10 days of fermentation with
      Phanerochaete chrysosporium and Trametes versicolor, and 15 days with Trametes
      hirsute. The degradation rate of lignin in the fermented tobacco stalk was 37.70,
      51.56 and 53.75% with Trametes versicolor, Trametes hirsute and Phanerochaete
      chrysosporium, respectively. Meanwhile, 24.28% hemicellulose was degraded by
      Phanerochaete chrysosporium and 28.19% cellulose was removed by Trametes hirsute.
      Through the enzyme activity analysis, the main and highest ligninolytic enzymes
      produced by Phanerochaete chrysosporium, Trametes hirsute and Trametes versicolor
      were lignin peroxidase (88.62 U . L-1), manganese peroxidase (100.95 U . L-1) and
      laccase (745.65 U . L-1). Meanwhile, relatively high and stable cellulase
      activity was also detected during the fermentation with Phanerochaete
      chrysosporium, and the highest endoglucanase, exoglucanase and filter paper
      enzyme activities were 0.38 U . mL-1, 0.45 U . mL-1 and 0.35U . mL-1,
      respectively. Moreover, the products in the fermentation of tobacco stalk with P.
      chrysosporium were identified with GC-MS, besides the chemicals produced in the
      degradation of lignin and nicotine, some small molecular valuable chemicals and
      fatty acid were also detected. CONCLUSIONS: Our study developed a new method for
      the degradation and detoxification of tobacco stalk by fermentation with white
      rot fungi Phanerochaete chrysosporium and Trametes hirsute. The different
      oxidative enzymes and chemical products detected during the degradation indicated
      a possible pathway for the utilization of tobacco stalk.

PMID- 27871280
TI  - Comparing conVEntional RadioTherapy with stereotactIC body radiotherapy in
      patients with spinAL metastases: study protocol for an randomized controlled
      trial following the cohort multiple randomized controlled trial design.
AB  - BACKGROUND: Standard radiotherapy is the treatment of first choice in patients
      with symptomatic spinal metastases, but is only moderately effective.
      Stereotactic body radiation therapy is increasingly used to treat spinal
      metastases, without randomized evidence of superiority over standard
      radiotherapy. The VERTICAL study aims to quantify the effect of stereotactic
      radiation therapy in patients with metastatic spinal disease. METHODS/DESIGN:
      This study follows the 'cohort multiple Randomized Controlled Trial' design. The
      VERTICAL study is conducted within the PRESENT cohort. In PRESENT, all patients
      with bone metastases referred for radiation therapy are enrolled. For each
      patient, clinical and patient-reported outcomes are captured at baseline and at
      regular intervals during follow-up. In addition, patients give informed consent
      to be offered experimental interventions. Within PRESENT, 110 patients are
      identified as a sub cohort of eligible patients (i.e. patients with unirradiated
      painful, mechanically stable spinal metastases who are able to undergo
      stereotactic radiation therapy). After a protocol amendment, also patients with
      non-spinal bony metastases are eligible. From the sub cohort, a random selection
      of patients is offered stereotactic radiation therapy (n = 55), which patients
      may accept or refuse. Only patients accepting stereotactic radiation therapy sign
      informed consent for the VERTICAL trial. Non-selected patients (n = 55) receive
      standard radiotherapy, and are not aware of them serving as controls. Primary
      endpoint is pain response after three months. Data will be analyzed by intention
      to treat, complemented by instrumental variable analysis in case of substantial
      refusal of the stereotactic radiation therapy in the intervention arm.
      DISCUSSION: This study is designed to quantify the treatment response after
      (stereotactic) radiation therapy in patients with symptomatic spinal metastases.
      This is the first randomized study in palliative care following the cohort
      multiple Randomized Controlled Trial design. This design addresses common
      difficulties associated with classic pragmatic randomized controlled trials, such
      as disappointment bias in patients allocated to the control arm, slow
      recruitment, and poor generalizability. TRIAL REGISTRATION: The Netherlands
      Trials Register number NL49316.041.14. ClinicalTrials.gov registration number
      NCT02364115 . Date of trial registration February 1, 2015.

PMID- 27871282
TI  - A mother's choice: a qualitative study of mothers' health seeking behaviour for
      their children with acute diarrhoea.
AB  - BACKGROUND: Diarrhoea presents a considerable health risk to young children and
      is one of the leading causes of infant mortality. Although proven cost-effective
      interventions exist, South Africa is yet to reach the Sustainable Development
      Goals set for the elimination of preventable under-five mortality and water-borne
      diseases. The rural study area in the Eastern Cape of South Africa continues to
      have a parallel health system comprising traditional and modern healthcare
      services. It is in this setting that this study aimed to qualitatively examine
      the beliefs surrounding and perceived quality of healthcare accessed for
      children's acute diarrhoea. METHODS: Purposive sampling was used to select
      participants for nine focus-group-discussions with mothers of children less than
      5 years old and 11 key-informant-interviews with community members and
      traditional and modern practitioners. The focus-group-discussions and interviews
      were held to explore the reasons why mothers seek certain types of healthcare for
      children with diarrhoea. Data was analysed using manual thematic coding methods.
      RESULTS: It was found that seeking healthcare from traditional practitioners is
      deeply ingrained in the culture of the society. People's beliefs about the
      causative agents of diarrhoea are at the heart of seeking care from traditional
      practitioners, often in order to treat supposed supernatural causes. A
      combination of care-types is acceptable to the community, but not necessarily to
      modern practitioners, who are concerned about the inclusion of unknown
      ingredients and harmful substances in some traditional medicines, which could be
      toxic to children. These factors highlight the complexity of regulating
      traditional medicine. CONCLUSION: South African traditional practitioners can be
      seen as a valuable human resource, especially as they are culturally accepted in
      their communities. However due to the variability of practices amongst
      traditional practitioners and some reluctance on the part of modern practitioners
      regulation and integration may prove complex.

PMID- 27871281
TI  - Physical multimorbidity and psychosis: comprehensive cross sectional analysis
      including 242,952 people across 48 low- and middle-income countries.
AB  - BACKGROUND: In people with psychosis, physical comorbidities, including
      cardiovascular and metabolic diseases, are highly prevalent and leading
      contributors to the premature mortality encountered. However, little is known
      about physical health multimorbidity in this population or in people with
      subclinical psychosis and in low- and middle-income countries (LMICs). This study
      explores physical health multimorbidity patterns among people with psychosis or
      subclinical psychosis. METHODS: Overall, data from 242,952 individuals from 48
      LMICs, recruited via the World Health Survey, were included in this cross
      sectional study. Participants were subdivided into those (1) with a lifetime
      diagnosis of psychosis ("psychosis"); (2) with more than one psychotic symptom in
      the past 12 months, but no lifetime diagnosis of psychosis ("subclinical
      psychosis"); and (3) without psychotic symptoms in the past 12 months or a
      lifetime diagnosis of psychosis ("controls"). Nine operationalized somatic
      disorders were examined: arthritis, angina pectoris, asthma, diabetes, chronic
      back pain, visual impairment, hearing problems, edentulism, and tuberculosis. The
      association between psychosis and multimorbidity was assessed by multivariable
      logistic regression analysis. RESULTS: The prevalence of multimorbidity (i.e.,
      two or more physical health conditions) was: controls = 11.4% (95% CI, 11.0
      11.8%); subclinical psychosis = 21.8% (95% CI, 20.6-23.0%), and psychosis = 36.0%
      (95% CI, 32.1-40.2%) (P < 0.0001). After adjustment for age, sex, education,
      country-wise wealth, and country, subclinical psychosis and psychosis were
      associated with 2.20 (95% CI, 2.02-2.39) and 4.05 (95% CI, 3.25-5.04) times
      higher odds for multimorbidity. Moreover, multimorbidity was increased in
      subclinical and established psychosis in all age ranges (18-44, 45-64, >= 65
      years). However, multimorbidity was most evident in younger age groups, with
      people aged 18-44 years with psychosis at greatest odds of physical health
      multimorbidity (OR = 4.68; 95% CI, 3.46-6.32). CONCLUSIONS: This large
      multinational study demonstrates that physical health multimorbidity is increased
      across the psychosis-spectrum. Most notably, the association between
      multimorbidity and psychosis was stronger among younger adults, thus adding
      further impetus to the calls for the early intervention efforts to prevent the
      burden of physical health comorbidity at later stages. Urgent public health
      interventions are necessary not only for those with a psychosis diagnosis, but
      also for subclinical psychosis to address this considerable public health
      problem.

PMID- 27871283
TI  - Improving the quality of primary care by allocating performance-based targets, in
      a diverse insured population.
AB  - BACKGROUND: Primary Care Health organizations, operating under universal coverage
      and a regulated package of benefits, compete mainly over quality of care.
      Monitoring, primary care clinical performance, has been repeatedly proven
      effective in improving the quality of care. In 2004, Maccabi Healthcare Services
      (MHS), the second largest Israeli HMO, launched its Performance Measurement
      System (PMS) based on clinical quality indicators. A unique module was built in
      the PMS to adjust for case mix while tailoring targets to the local units. This
      article presents the concept and formulas developed to adjust targets to the
      units' current performance, and analyze change in clinical indicators over a six
      year period, between sub-population groups. METHODS: Six process and intermediate
      outcome indicators, representing screening for breast and colorectal cancer and
      care for patients with diabetes and cardiovascular disease, were selected and
      analyzed for change over time (2003-2009) in overall performance, as well as the
      difference between the lowest and the highest socio-economic ranks (SERs) and
      Arab and non-Arab members. RESULTS: MHS demonstrated a significant improvement in
      the selected indicators over the years. Performance of members from low SERs and
      Arabs improved to a greater extent, as compared to members from high ranks and
      non-Arabs, respectively. CONCLUSION: The performance measurement system, with its
      module for tailoring of units' targets, served as a managerial vehicle for
      bridging existing gaps by allocating more resources to lower performing units.
      This concept was proven effective in improving performance while reducing
      disparities between diverse population groups.

PMID- 27871284
TI  - Radiographic results after plaster cast fixation for 10 days versus 1 month in
      reduced distal radius fractures: a prospective randomised study.
AB  - BACKGROUND: The aim of this study was to examine whether reduced distal radius
      fractures can be treated with early mobilisation without affecting the
      radiographic results. METHODS: In a prospective randomised study, 109 patients
      (mean age 65.8 (range 50-92)) with moderately displaced distal radius fractures
      were treated with closed reduction and plaster cast fixation for about 10 days
      (range 8-13 days) followed by randomisation to one of two groups: early
      mobilisation (n = 54, active group) or continued plaster cast fixation for
      another 3 weeks (n = 55, control group). RESULTS: For three patients in the
      active group (6%), treatment proved unsuccessful because of severe displacement
      of the fracture (n = 2) or perceived instability (n = 1). From 10 days to 1
      month, i.e. the only period when the treatment differed between the two groups,
      the active group displaced significantly more in dorsal angulation (4.5 degrees ,
      p < 0.001), radial angulation (2.0 degrees , p < 0.001) and axial compression
      (0.5 mm, p = 0.01) compared with the control group. However, during the entire
      study period (i.e. from admission to 12 months), the active group displaced
      significantly more than the controls only in radial angulation (3.2 degrees , p =
      0.002) and axial compression (0.7 mm, p = 0.02). CONCLUSIONS: Early mobilisation
      10 days after reduction of moderately displaced distal radius fractures resulted
      in both an increased number of treatment failures and increased displacement in
      radial angulation and axial compression as compared with the control group.
      Mobilisation 10 days after reduction cannot be recommended for the routine
      treatment of reduced distal radius fractures. TRIAL REGISTRATION:
      ClinicalTrail.gov, NCT02798614 . Retrospectively registered 16 June 2016.

PMID- 27871285
TI  - Next-generation sequencing in thyroid cancer.
AB  - Next-generation sequencing (NGS) in thyroid cancer allows for simultaneous high
      throughput sequencing analysis of variable genetic alterations and provides a
      comprehensive understanding of tumor biology. In thyroid cancer, NGS offers
      diagnostic improvements for fine needle aspiration (FNA) cytology of thyroid with
      indeterminate features. It also contributes to patient management, providing risk
      stratification of patients based on the risk of malignancy. Furthermore, NGS has
      been adopted in cancer research. It is used in molecular tumor classification,
      and molecular prediction of recurrence and metastasis in papillary thyroid
      carcinoma. This review covers previous NGS analyses in variable types of thyroid
      cancer, where samples including FNA cytology, fresh frozen tissue, and formalin
      fixed, paraffin-embedded tissues were used. This review also focuses on the
      clinical and research implications of using NGS to study and treat thyroid
      cancer.

PMID- 27871286
TI  - Maxillary calcifying epithelial odontogenic tumor with sinus and buccal vestibule
      extension: a case report and immunohistochemical study.
AB  - BACKGROUND: Calcifying epithelial odontogenic tumor (CEOT) is a rare benign
      neoplasia, locally aggressive, that tends to invade bone and adjacent soft
      tissues. This case report describes the thirteenth known case of CEOT with
      maxillary sinus extension and the second one that also involves the buccal
      vestibule mucosa with peculiar histopathological and immunohistochemical data.
      CASE PRESENTATION: Here we report the case of a 45-year-old female with a CEOT
      diagnosed and treated at the Oral & Maxillofacial Surgery Department, County
      Clinical Emergency Hospital of Craiova, Romania. The clinical and imaging
      investigation revealed an intraosseous tumor developed from the left posterior
      maxilla with maxillary sinus and buccal vestibule mucosa extension.
      Histopathology found an epithelium-rich CEOT variant, but with scattered S100
      positive clear cells, focal small rounded cementum-like deposits and areas with
      some degree of nuclear pleomorphism. The immunohistochemical investigations
      emphasised its local aggressiveness behavior with involvement of multiple
      molecular mechanisms that underlie tumor invasiveness. A subtotal maxillectomy
      was performed followed by defect reconstruction. CONCLUSIONS: We discuss the
      relevant clinicopathological features of an aggressive rare case of CEOT with
      maxillary sinus extension and buccal vestibule mucosa involvement. The
      immunohistochemical study suggests its utility in attempting to assess the degree
      of local tumor aggressiveness and thus in adopting the most efficient therapeutic
      attitude.

PMID- 27871287
TI  - Perspectives on death and dying: a study of resident comfort with End-of-life
      care.
AB  - BACKGROUND: Despite the benefits to early palliative care in the treatment of
      terminal illness, barriers to timely hospice referrals exist. Physicians who are
      more comfortable having end-of-life (EOL) conversations are more likely to refer
      to hospice. However, very little is known about what factors influence comfort
      with EOL care. METHODS: An anonymous survey was sent to all the residents and
      fellows at a single institution. Self-reported education, experience and comfort
      with EOL care was assessed. Using multivariate logistic regression analysis,
      variables that influenced comfort with EOL conversations were analyzed. RESULTS:
      Most residents (88.1%) reported little to no classroom training on EOL care
      during residency. EOL conversations during residency were frequent (50.6%
      reported > 10) and mostly unsupervised (61.9%). In contrast, EOL conversations
      during medical school were infrequent (3.7% reported >10) and mostly supervised
      (78.6%). Most (54.3%) reported little to no classroom training on EOL care during
      medical school. Physicians that reported receiving education on EOL conversations
      during residency and those who had frequent EOL conversations during residency
      had significantly higher comfort levels having EOL conversations (p = 0.017 and p
      = 0.003, respectively). Likewise, residents that felt adequately prepared to have
      EOL conversations when graduating from medical school were more likely to feel
      comfortable (p = 0.030). CONCLUSIONS: Most residents had inadequate education in
      EOL conversation skills during medical school and residency. Despite the lack of
      training, EOL conversations during residency are common and often unsupervised.
      Those who reported more classroom training during residency on EOL skills had
      greater comfort with EOL conversations. Training programs should provide
      palliative care education to all physicians during residency and fellowship,
      especially for those specialties that are most likely to encounter patients with
      advanced terminal disease.

PMID- 27871288
TI  - Tissue specific expression of human fatty acid oxidation enzyme genes in late
      pregnancy.
AB  - BACKGROUND: Abnormal fatty acid oxidation (FAO) is associated with maternal and
      fetal complications during pregnancy. The contribution of maternal and fetal
      tissues to FAO capacity during late pregnancy is important to understand the
      pathophysiology of pregnancy-associated complications. The aim of this study was
      to determine the expression levels of mitochondrial FAO enzymes in maternal and
      fetal tissues during late normal pregnancy. METHODS: We have measured by Real
      time PCR the levels of long- and medium -chain acyl-CoA dehydrogenase (LCHAD and
      MCAD), two acyl-CoA dehydrogenases that catalyze the initial step in the
      mitochondrial FAO spiral. RESULTS: LCHAD and MCAD were expressed in maternal
      skeletal muscle, subcutaneous adipose tissue, placenta, and maternal and fetal
      blood cells. LCHAD gene expression was four- to 16-fold higher than MCAD gene
      expression in placenta, adipose tissue and skeletal muscle. In contrast, MCAD
      gene expression was ~5-fold higher in fetal blood than maternal blood (p = 0.02),
      whereas LCHAD gene expression was similar between fetal blood and maternal blood
      (p =0.91). CONCLUSIONS: LCHAD and MCAD are differentially expressed in maternal
      and fetal tissues during normal late pregnancy, which may represent a metabolic
      adaptation in response to physiological maternal dyslipidemia during late
      pregnancy.

PMID- 27871289
TI  - Inhibition of STAT3- and MAPK-dependent PGE2 synthesis ameliorates phagocytosis
      of fibrillar beta-amyloid peptide (1-42) via EP2 receptor in EMF-stimulated N9
      microglial cells.
AB  - BACKGROUND: Prostaglandin E2 (PGE2)-involved neuroinflammatory processes are
      prevalent in several neurological conditions and diseases. Amyloid burden is
      correlated with the activation of E-prostanoid (EP) 2 receptors by PGE2 in
      Alzheimer's disease. We previously demonstrated that electromagnetic field (EMF)
      exposure can induce pro-inflammatory responses and the depression of phagocytosis
      in microglial cells, but the signaling pathways involved in phagocytosis of
      fibrillar beta-amyloid (fAbeta) in microglial cells exposed to EMF are poorly
      understood. Given the important role of PGE2 in neural physiopathological
      processes, we investigated the PGE2-related signaling mechanism in the
      immunomodulatory phagocytosis of EMF-stimulated N9 microglial cells (N9 cells).
      METHODS: N9 cells were exposed to EMF with or without pretreatment with the
      selective inhibitors of cyclooxygenase-2 (COX-2), Janus kinase 2 (JAK2), signal
      transducer and activator of transcription 3 (STAT3), and mitogen-activated
      protein kinases (MAPKs) and antagonists of PG receptors EP1-4. The production of
      endogenous PGE2 was quantified by enzyme immunoassays. The phagocytic ability of
      N9 cells was evaluated based on the fluorescence intensity of the engulfed
      fluorescent-labeled fibrillar beta-amyloid peptide (1-42) (fAbeta42) measured
      using a flow cytometer and a fluorescence microscope. The effects of
      pharmacological agents on EMF-activated microglia were investigated based on the
      expressions of JAK2, STAT3, p38/ERK/JNK MAPKs, COX-2, microsomal prostaglandin E
      synthase-1 (mPGES-1), and EP2 using real-time PCR and/or western blotting.
      RESULTS: EMF exposure significantly increased the production of PGE2 and
      decreased the phagocytosis of fluorescent-labeled fAbeta42 by N9 cells. The
      selective inhibitors of COX-2, JAK2, STAT3, and MAPKs clearly depressed PGE2
      release and ameliorated microglial phagocytosis after EMF exposure.
      Pharmacological agents suppressed the phosphorylation of JAK2-STAT3 and MAPKs,
      leading to the amelioration of the phagocytic ability of EMF-stimulated N9 cells.
      Antagonist studies of EP1-4 receptors showed that EMF depressed the phagocytosis
      of fAbeta42 through the PGE2 system, which is linked to EP2 receptors.
      CONCLUSIONS: This study indicates that EMF exposure could induce phagocytic
      depression via JAK2-STAT3- and MAPK-dependent PGE2-EP2 receptor signaling
      pathways in microglia. Therefore, pharmacological inhibition of PGE2 synthesis
      and EP2 receptors may be a potential therapeutic strategy to combat the
      neurobiological deterioration that follows EMF exposure.

PMID- 27871290
TI  - Heterozygous connexin 50 mutation affects metabolic syndrome attributes in
      spontaneously hypertensive rat.
AB  - BACKGROUND: Several members of connexin family of transmembrane proteins were
      previously implicated in distinct metabolic conditions. In this study we aimed to
      determine the effects of complete and heterozygous form of connexin50 gene (Gja8)
      mutation L7Q on metabolic profile and oxidative stress parameters in
      spontaneously hypertensive inbred rat strain (SHR). METHODS: Adult, standard chow
      fed male rats of SHR, heterozygous SHR-Dca+/- and SHR-Dca-/- coisogenic strains
      were used. At the age of 4 months, dexamethasone (2.6 MUg/ml) was administered in
      the drinking water for three days. The lipidemic profile (cholesterol and
      triacylglycerol concentration in 20 lipoprotein fractions, chylomicron, VLDL, LDL
      and HDL particle sizes) together with 33 cytokines and hormones in serum and
      several oxidative stress parameters in plasma, liver, kidney and heart were
      assessed. RESULTS: SHR and SHR-Dca-/- rats had similar concentrations of
      triacylglycerols and cholesterol in all major lipoprotein fractions. The
      heterozygotes reached significantly highest levels of total (SHR-Dca+/-: 51.3 +/-
      7.2 vs. SHR: 34.5 +/- 2.4 and SHR-Dca-/-: 34.4 +/- 2.5 mg/dl, p = 0.026),
      chylomicron and VLDL triacylglycerols. The heterozygotes showed significantly
      lowest values of HDL cholesterol (40.9 +/- 2.3 mg/dl) compared both to SHR (51.8
      +/- 2.2 mg/dl) and SHR-Dca-/- (48.6 +/- 2.7 mg/dl). Total and LDL cholesterol in
      SHR-Dca+/- was lower compared to SHR. Glucose tolerance was improved and insulin
      concentrations were lowest in SHR-Dca-/- (1.11 +/- 0.20 pg/ml) in comparison with
      both SHR (2.32 +/- 0.49 pg/ml) and SHR-Dca+/- (3.04 +/- 0.21 pg/ml). The
      heterozygous rats showed profile suggestive of increased oxidative stress as well
      as highest serum concentrations of several pro-inflammatory cytokines including
      interleukins 6, 12, 17, 18 and tumor necrosis factor alpha. CONCLUSIONS: Our
      results demonstrate that connexin50 mutation in heterozygous state affects
      significantly the lipid profile and the oxidative stress parameters in the
      spontaneously hypertensive rat strain.

PMID- 27871291
TI  - "A rising tide lifts all boats": establishing a multidisciplinary genomic tumor
      board for breast cancer patients with advanced disease.
AB  - BACKGROUND: Research suggests that multidisciplinary genomic tumor boards (MGTB)
      can inform cancer patient care, though little is known about factors influencing
      how MGTBs interpret genomic test results, make recommendations, and perceive the
      utility of this approach. This study's objective was to observe, describe, and
      assess the establishment of the Breast Multidisciplinary Genomic Tumor Board, the
      first MGTB focused on interpreting genomic test results for breast cancer
      patients with advanced disease. METHODS: We conducted a qualitative case study
      involving participant observation at monthly MGTB meetings from October 2013
      through November 2014 and interviews with 12 MGTB members. We analyzed social
      dynamics and interactions within the MGTB regarding interpretation of genomic
      findings and participants' views on effectiveness of the MGTB in using genomics
      to inform patient care. RESULTS: Twenty-two physicians, physician-scientists,
      basic scientists, bioethicists, and allied care professionals comprised the MGTB.
      The MGTB reviewed FoundationOneTM results for 40 metastatic breast cancer
      patients. Based on findings, the board mostly recommended referring patients to
      clinical trials (34) and medical genetics (15), and Food and Drug Administration
      approved (FDA) breast cancer therapies (13). Though multidisciplinary,
      recommendations were driven by medical oncologists. Interviewees described
      providing more precise care recommendations and professional development as
      advantages and the limited actionability of genomic test results as a challenge
      for the MGTB. CONCLUSIONS: Findings suggest both feasibility and desirability of
      pooling professional expertise in genomically-guided breast cancer care and
      challenges to institutionalizing a Breast MGTB, specifically in promoting
      interdisciplinary contributions and managing limited actionability of genomic
      test results for patients with advanced disease.

PMID- 27871292
TI  - Ability of ELISAs to detect antibodies against porcine respiratory and
      reproductive syndrome virus in serum of pigs after inactivated vaccination and
      subsequent challenge.
AB  - BACKGROUND: In this study, six enzyme-linked immunosorbent assays (ELISA),
      intended for routine porcine reproductive and respiratory syndrome virus (PRRSV)
      herd monitoring, are tested for their ability to detect PRRSV specific antibodies
      in the serum of pigs after vaccination with an inactivated PRRSV type 1 vaccine
      and subsequent infection with a highly pathogenic (HP) PRRSV field strain. For
      this reason, ten piglets (group V) from a PRRSV negative herd were vaccinated
      twice at the age of 2 and 4 weeks with an inactivated PRRSV vaccine. Ten
      additional piglets (group N) from the same herd remained unvaccinated. Three
      weeks after second vaccination, each of the piglets received an intradermal
      application of an HP PRRSV field strain. Serum samples were taken before first
      vaccination as well as before and 3, 7, 10 and 14 days after HP PRRSV
      application. All serum samples were tested for PRRSV RNA by reverse transcriptase
      quantitative polymerase chain reaction (RT-qPCR) as well as for PRRSV antibodies
      with all six study ELISAs. RESULTS: At the beginning of the study (before
      vaccination), all of the piglets were PRRSV antibody negative with all study
      ELISAs. They also tested negative for PRRSV RNA measured by RT-qPCR. From day 3
      after HP PRRSV application until the end of the study, a viremia was detected by
      RT-qPCR in all of the piglets. On day 0 (day of HP PRRSV application), nine out
      of ten piglets of the pre-vaccinated group tested PRRSV antibody positive with
      one of the tested ELISAs, although with lower S/P values than after infection. On
      day 10 after HP PRRSV application, all study ELISAs except one had significantly
      higher S/P or OD values, respectively more positive samples, in group V than in
      group N. CONCLUSIONS: Only one of the tested ELISAs was able to detect reliably
      PRRSV antibodies in pigs vaccinated with an inactivated PRRSV vaccine. With most
      of the tested ELISAs, higher S/P values respectively more positive samples after
      PRRSV infection were seen in the pre-vaccinated group than in the non-vaccinated.

PMID- 27871293
TI  - Genetic and epigenetic alterations in the GNAS locus and clinical consequences in
      Pseudohypoparathyroidism: Italian common healthcare pathways adoption.
AB  - BACKGROUND: Genetic and epigenetic alterations in the GNAS locus are responsible
      for the Gsalpha protein dysfunctions causing Pseudohypoparathyroidism (PHP) type
      Ia/c and Ib, respectively. For these heterogeneous diseases characterized by
      multiple hormone resistances and Albright's Hereditary Osteodystrophy (AHO) the
      current classification results inadequate because of the clinical overlap between
      molecular subtypes and a standard clinical approach is still missing. In the
      present paper several members of the Study Group Endocrine diseases due to
      altered function of Gsalpha protein of the Italian Society of Pediatric
      Endocrinology and Diabetology (ISPED) have reviewed and updated the clinical
      molecular data of the largest case series of (epi)/genetically characterized
      AHO/PHP patients; they then produced a common healthcare pathway for patients
      with these disorders. METHODS: The molecular analysis of the GNAS gene and locus
      identified the causal alteration in 74 subjects (46 genetic and 28 epigenetic
      mutations). The clinical data at the diagnosis and their evolution during up to
      15 years follow-up were collected using two different cards. RESULTS: In patients
      with genetic mutations the growth impairment worsen during the time, while
      obesity prevalence decreases; subcutaneous ossifications seem specific for this
      group. Brachydactyly has been detected in half of the subjects with epigenetic
      alterations, in which the disease overts later in life, often with symptomatic
      hypocalcaemia, and also early TSH and GHRH resistances have been recorded.
      CONCLUSIONS: A dedicated healthcare pathway addressing all these aspects in a
      systematic way would improve the clinical management, allowing an earlier
      recognition of some PHP features, the optimization of their medical treatment and
      a better clinical-oriented molecular analysis. Furthermore, standardized follow
      up data would provide new insight into less known aspects.

PMID- 27871294
TI  - Newly designed retentive posts of mandibular reconstruction plate in oral cancer
      patients based on preliminary FEM study.
AB  - BACKGROUND: The reconstruction of a large mandibular defect poses a challenging
      issue in oral cancer ablation surgery. One popular option for mandibular
      continuity reconstruction after tumor resection involves the use of a
      reconstruction plate (R-plate), which maintains space and contour without bone
      harvesting. An R-plate, however, cannot provide final functional loading
      rehabilitation with implants or dentures. METHODS: We suggest a new method of
      functional mandibular reconstruction using retentive posts and an upper
      prosthesis. The finite element method (FEM) was used to optimize the design.
      Surgery was needed to adapt the retentive posts. Prosthodontic procedures were
      required for the upper prosthesis. RESULTS: Eight patients were treated with
      retentive posts and prostheses. All patients underwent wide resections of the
      mandible, and reconstruction with an R-plate and microvascular soft tissue
      transfer. We adapted the retentive posts on an R-plate and fabricated the upper
      prostheses with a flexible denture or a fixed resin prosthesis. Finally, the
      patients had functional rehabilitation, which restored proper mastication.
      CONCLUSIONS: The retentive posts of the R-plate and upper prosthesis allow
      functional dental rehabilitation without the need for a bone graft. Virtual
      simulation using FEM will help to design and optimize the retentive posts. Two or
      three regular size posts are suitable for the quadrant jaw. This first
      preliminary step will allow improved patient-specific retentive post designs in
      the near future.

PMID- 27871296
TI  - Work hours and turnover intention among hospital physicians in Taiwan: does
      income matter?
AB  - BACKGROUND: Physician shortage has become an urgent and critical challenge to
      many countries. According to the workforce dynamic model, long work hours may be
      one major pressure point to the attrition of physicians. Financial incentive is a
      common tool to human power retention. Therefore, this large-scale physician study
      investigated how pay satisfaction may influence the relationship between work
      hours and hospital physician's turnover intention. METHODS: Data were obtained
      from a nationwide survey of full-time hospital staff members working at 100
      hospitals in Taiwan. The analysis sample comprised 2423 full-time physicians.
      Dependent variable was degree of the physicians' turnover intention to leave the
      current hospital. The pay satisfaction was assessed by physicians themselves. We
      employed ordinal logistic regression models to analyze the association between
      the number of work hours and turnover intention. To consider the cluster effect
      of hospitals, we used the "gllamm" command in the statistical software package
      Stata Version 12.1. RESULTS: The results show that 351 (14.5%) of surveyed
      physicians reported strong intention to leave current hospital. The average work
      hours per week among hospital physicians was 59.8 h. As expected, work hours
      exhibited an independent relationship with turnover intention. More importantly,
      pay satisfaction could not effectively moderate the positive relationship between
      work hours and intentions to leave current hospital. CONCLUSIONS: The findings
      show that overtime work is prevalent among hospital physicians in Taiwan. Both
      the Taiwanese government and hospitals must take action to address the emerging
      problem of physician high turnover rate. Furthermore, hospitals should not
      consider relying solely on financial incentives to solve the problem. This study
      encouraged tackling work hour problem, which would lead to the possibility of
      solving high turnover intention among hospital physicians in Taiwan.

PMID- 27871295
TI  - Anaplasma phagocytophilum in sheep and goats in central and southeastern China.
AB  - BACKGROUND: Anaplasma phagocytophilum is wide spread throughout the world and
      impacts both human and animal health. Several distinct ecological clusters and
      ecotypes of the agent have been established on the basis of various genetic loci.
      However, information on the genetic variability of A. phagocytophilum isolates in
      China represents a gap in knowledge. The objective of this study was to determine
      the prevalence and genetic characterization of A. phagocytophilum in small
      ruminants in central and southeastern China. METHODS: The presence of A.
      phagocytophilum was determined in 421 blood samples collected from small
      ruminants by PCR. Positive samples were genetically characterized based on 16S
      rRNA and groEL genes. Statistical analyses were conducted to identify ecotypes of
      A. phagocytophilum strains, to assess their host range and zoonotic potential.
      RESULTS: Out of 421 sampled small ruminants, 106 (25.2%) were positive for A.
      phagocytophilum. The positive rate was higher in sheep (35.1%, 40/114) than in
      goats (26.4%, 66/307) (P < 0.05). Sequence analyses revealed that the isolates
      identified in this study were placed on two separate clades, indicating that two
      16S rRNA variants of A. phagocytophilum were circulating in small ruminants in
      China. However, analysis using obtained groEL sequences in this study formed one
      cluster, which was separate from other known ecotypes reported in Europe. In
      addition, a novel Anaplasma sp. was identified and closely related to an isolate
      previously reported in Hyalomma asiaticum, which clustered independently from all
      recognized Anaplasma species. CONCLUSIONS: A molecular survey of A.
      phagocytophilum was conducted in sheep and goats from ten provinces in central
      and southeastern China. Two 16S rRNA variants and a new ecotype of A.
      phagocytophilum were identified in small ruminants in China. Moreover, a
      potential novel Anaplasma species was reported in goats. Our findings provide
      additional information on the complexity of A. phagocytophilum in terms of
      genetic diversity in China.

PMID- 27871297
TI  - AQP5-1364A/C polymorphism and the AQP5 expression influence sepsis survival and
      immune cell migration: a prospective laboratory and patient study.
AB  - BACKGROUND: The C-allele of the aquaporin (AQP5) -1364A/C polymorphism is
      associated with decreased AQP5 expression but increased 30-day survival in
      patients with severe sepsis. AQP5 expression might affect survival via an impact
      on cell migration. Consequently, we tested the hypothesis that (1) Aqp5 knockout
      (KO) compared to wild type (WT) mice show an increased survival following
      lipopolysaccharide (LPS) administration, and that (2) AQP5 expression and the
      AQP5 -1364A/C polymorphism alters immune cell migration. METHODS: We investigated
      Aqp5-KO and wild type mice after intraperitoneal injection of either E.coli
      lipopolysaccharide (LPS, serotype O127:B8, 20 mg/kg) or saline. Furthermore,
      neutrophils of volunteers with the AA-AQP5 or AC/CC-AQP5- genotype were incubated
      with 10-8 M Chemotactic peptide (fMLP) and their migration was assessed by a
      filter migration assay. Additionally, AQP5 expression after fMLP incubation was
      analyzed by RT-PCR and Western blot. Moreover, migration of AQP5 overexpressing
      Jurkat cells was studied after SDF-1alpha-stimulation. We used exact Wilcoxon
      Mann-Whitney tests; exact Wilcoxon signed-rank tests and the Kaplan-Meier
      estimator for statistical analysis. RESULTS: Fifty-six percent of Aqp5-KO but
      only 22% of WT mice survived following LPS-injection. WT mice showed increased
      neutrophil migration into peritoneum and lung compared to Aqp5-KO mice. Target
      oriented migration of neutrophils was seen after 0.5 h in AA-genotype cells but
      only after 1.5 h in AC/CC-genotype cells, with a threefold lower migrating cell
      count. AQP5 overexpressing Jurkat cells showed a 2.4 times stronger migration
      compared to native Jurkat cells. CONCLUSION: The AQP5 genotype may influence
      survival following LPS by altering neutrophil cell migration. Trial registration
      DRKS00010437. Retrospectively registered 26 April 2016.

PMID- 27871298
TI  - Socioeconomic variation in incidence of primary and secondary major
      cardiovascular disease events: an Australian population-based prospective cohort
      study.
AB  - BACKGROUND: Cardiovascular disease (CVD) disproportionately affects disadvantaged
      people, but reliable quantitative evidence on socioeconomic variation in CVD
      incidence in Australia is lacking. This study aimed to quantify socioeconomic
      variation in rates of primary and secondary CVD events in mid-age and older
      Australians. METHODS: Baseline data (2006-2009) from the 45 and Up Study, an
      Australian cohort involving 267,153 men and women aged >= 45, were linked to
      hospital and death data (to December 2013). Outcomes comprised first event -
      death or hospital admission - for major CVD combined, as well as myocardial
      infarction and stroke, in those with and without prior CVD (secondary and primary
      events, respectively). Cox regression estimated hazard ratios (HRs) for each
      outcome in relation to education (and income and area-level disadvantage),
      separately by age group (45-64, 65-79, and >= 80 years), adjusting for age and
      sex, and additional sociodemographic factors. RESULTS: There were 18,207 primary
      major CVD events over 1,144,845 years of follow-up (15.9/1000 person-years), and
      20,048 secondary events over 260,357 years (77.0/1000 person-years). For both
      primary and secondary events, incidence increased with decreasing education, with
      the absolute difference between education groups largest for secondary events.
      Age-sex adjusted hazard ratios were highest in the 45-64 years group: for major
      CVDs, HR (no qualifications vs university degree) = 1.62 (95% CI: 1.49-1.77) for
      primary events, and HR = 1.49 (1.34-1.65) for secondary events; myocardial
      infarction HR = 2.31 (1.87-2.85) and HR = 2.57 (1.90-3.47) respectively; stroke
      HR = 1.48 (1.16-1.87) and HR = 1.97 (1.42-2.74) respectively. Similar but
      attenuated results were seen in older age groups, and with income. For area-level
      disadvantage, CVD gradients were weak and non-significant in older people (> 64
      years). CONCLUSIONS: Individual-level data are important for quantifying
      socioeconomic variation in CVD incidence, which is shown to be substantial among
      both those with and without prior CVD. Findings reinforce the opportunity for,
      and importance of, primary and secondary prevention and treatment in reducing
      socioeconomic variation in CVD and consequently the overall burden of CVD
      morbidity and mortality in Australia.

PMID- 27871299
TI  - Implementation and acceptability of strategies instituted for engaging men in
      family planning services in Kibaha district, Tanzania.
AB  - BACKGROUND: Men as the main decision makers in most of African families have an
      important role to play towards acceptance of family planning methods. This study
      sought to identify strategies used to engage men in family planning services and
      determine the extent to which men in Kibaha district in Tanzania accept these
      interventions. METHODS: We conducted a cross sectional study using both
      quantitative and qualitative techniques. We used a questionnaire to interview a
      random sample of 365 of currently married or cohabiting men who had at least one
      child under the age of five years. We further conducted in-depth interviews with
      health workers involved in delivering reproductive health services as well as
      community dispensers of family planning commodities. Descriptive analysis was
      used to determine the extent to which men were engaged in family planning
      services. The data from the indepth interviews were analysed manually according
      to the predetermined themes, guided by the grounded theory to identify the
      existing strategies used to encourage male involvement in family planning
      services. RESULTS: According to the key informants, strategies that are used to
      encourage men to engage in family planning services include invitations through
      their spouses, either verbally or by using partner notification cards,
      incorporating family planning messages during monthly meetings and community
      outreach reproductive health programs. Of 365 men responding to the
      questionnaire, only 31 (8.4%) said they were invited to accompany their spouses
      to family planning clinics. Among them, 71% (22/31) visited family planning
      clinics. A third (32%) of the respondents had heard of community health meetings
      and only 20.7% of them attended these meetings. More than a third (12/34) of men
      who attended these meeting asserted that family planning messages targeting men
      featured in the agenda and subsequently half of them visited health facilities
      for family planning services. CONCLUSIONS: Existing strategies such as
      invitations to clinics and community sensitization have shown to encourage men to
      engage in family planning services. However, these interventions reach few men
      and hence there is a need to rolling them up to improve uptake of family planning
      services.

PMID- 27871300
TI  - PI3 kinase pathway regulated miRNome in glioblastoma: identification of miR-326
      as a tumour suppressor miRNA.
AB  - BACKGROUND: Glioblastomas (GBM) continue to remain one of the most dreaded
      tumours that are highly infiltrative in nature and easily preclude comprehensive
      surgical resection. GBMs pose an intricate etiology as they are being associated
      with a plethora of genetic and epigenetic lesions. Misregulation of the PI3
      kinase pathway is one of the most familiar events in GBM. While the PI3 kinase
      signalling regulated pathways and genes have been comprehensively studied, its
      impact on the miRNome is yet to be explored. The objective of this study was to
      elucidate the PI3 kinase pathway regulated miRNAs in GBM. METHODS: miRNA
      expression profiling was conducted to monitor the differentially regulated miRNAs
      upon PI3 kinase pathway abrogation. qRT-PCR was used to measure the abundance of
      miR-326 and its host gene encoded transcript. Proliferation assay, colony
      suppression assay and wound healing assay were carried out in pre-miR transfected
      cells to investigate its role in malignant transformation. Potential targets of
      miR-326 were identified by transcriptome analysis of miR-326 overexpressing cells
      by whole RNA sequencing and selected targets were validated. Several publically
      available data sets were used for various investigations described above.
      RESULTS: We identified several miRNA that were regulated by PI3 kinase pathway.
      miR-326, a GBM downregulated miRNA, was validated as one of the miRNAs whose
      expression was alleviated upon abrogation of the PI3 kinase pathway.
      Overexpression of miR-326 resulted in reduced proliferation, colony suppression
      and hindered the migration capacity of glioma cells. Arrestin, Beta 1 (ARRB1),
      the host gene of miR-326, was also downregulated in GBM and interestingly, the
      expression of ARRB1 was also alleviated upon inhibition of the PI3 kinase
      pathway, indicating similar regulation pattern. More importantly, miR-326
      exhibited a significant positive correlation with ARRB1 in terms of its
      expression. Transcriptome analysis upon miR-326 overexpression coupled with
      integrative bioinformatics approach identified several putative targets of miR
      326. Selected targets were validated and interestingly found to be upregulated in
      GBM. CONCLUSIONS: Taken together, our study uncovered the PI3 kinase regulated
      miRNome in GBM. miR-326, a PI3 kinase pathway inhibited miRNA, was demonstrated
      as a tumour suppressor miRNA in GBM.

PMID- 27871301
TI  - An innovative and collaborative partnership between patients with rare disease
      and industry-supported registries: the Global aHUS Registry.
AB  - BACKGROUND: Patients are becoming increasingly involved in research which can
      promote innovation through novel ideas, support patient-centred actions, and
      facilitate drug development. For rare diseases, registries that collect data from
      patients can increase knowledge of the disease's natural history, evaluate
      clinical therapies, monitor drug safety, and measure quality of care. The active
      participation of patients is expected to optimise rare-disease management and
      improve patient outcomes. However, few reports address the type and frequency of
      interactions involving patients, and what research input patient groups have.
      Here, we describe a collaboration between an international group of patient
      organisations advocating for patients with atypical haemolytic uraemic syndrome
      (aHUS), the aHUS Alliance, and an international aHUS patient registry
      (ClinicalTrials.gov NCT01522183). RESULTS: The aHUS Registry Scientific Advisory
      Board (SAB) invited the aHUS Alliance to submit research ideas important to
      patients with aHUS. This resulted in 24 research suggestions from patients and
      patient organisations being presented to the SAB. The proposals were classified
      under seven categories, the most popular of which were understanding factors that
      cause disease manifestations and learning more about the clinical and
      psychological/social impact of living with the disease. Subsequently, aHUS
      Alliance members voted for up to five research priorities. The top priority was:
      "What are the outcomes of a transplant without eculizumab and what non-kidney
      damage is likely in patients with aHUS?". This led directly to the initiation of
      an ongoing analysis of the data collected in the Registry on patients with kidney
      transplants. CONCLUSION: This collaboration resulted in several topics proposed
      by the aHUS Alliance being selected as priority activities for the aHUS Registry,
      with one new analysis already underway. A clear pathway was established for
      engagement between a patient advocacy group and an international research
      network. This should ensure the development of a long-term partnership which
      clearly benefits both groups.

PMID- 27871302
TI  - Glycopyrrolate in comparison to hyoscine hydrobromide and placebo in the
      treatment of hypersalivation induced by clozapine (GOTHIC1): study protocol for a
      randomised controlled feasibility study.
AB  - BACKGROUND: Clozapine is the only medication licensed for the treatment of
      resistant schizophrenia in the UK. Although efficacious, a common and unpopular
      side effect of clozapine treatment is clozapine-induced hypersalivation (CIH),
      which can contribute to non-adherence. The standard treatment for CIH in the UK
      is hyoscine hydrobromide but this may aggravate cognitive deficits in patients
      with schizophrenia while glycopyrrolate may be an effective alternative with a
      more tolerable side effect profile. There is currently no convincing evidence for
      hyoscine, or any other medication, as an effective treatment for CIH.
      METHODS/DESIGN: This is a multicentre randomised, double-blind, placebo
      controlled feasibility study of glycopyrronium bromide (glycopyrrolate) and
      hyoscine hydrobromide (hyoscine) in patients with clozapine-induced
      hypersalivation. We aim to recruit 42 patients who have been prescribed clozapine
      and are experiencing hypersalivation, and randomise them to one of three study
      arms (either hyoscine, glycopyrrolate or placebo). The primary outcome measures
      will be the participant recruitment and attrition rates, and the secondary
      outcome will be the metrics of the daytime hypersalivation measure. After a 1
      week washout period (discontinuing CIH medication, if any), there will be a 4
      week treatment period where participants will be titrated up to the maximum
      tolerated dose of hyoscine, glycopyrrolate or placebo. Measurements of daytime
      salivation, nocturnal salivation, cognition and side effects will be taken during
      home visits in week 2 and week 5. Information on salivation and side effects will
      also be taken through telephone calls in week 3 and week 4. To gather information
      on the experience of study participants, exit interviews will also be requested
      with all participants who drop out of the study and a sample of participants who
      complete the study. DISCUSSION: There is currently no convincing evidence for
      hyoscine, or any other medication, as an effective treatment for CIH. There is
      promising evidence that glycopyrrolate may be more successful in the treatment of
      CIH causing fewer cognitive side effects. We propose to conduct a randomised
      placebo-controlled feasibility study of glycopyrrolate and hyoscine in the
      treatment of clozapine-induced hypersalivation to inform the design of a future
      efficacy trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613494 , 23 November
      2015.

PMID- 27871303
TI  - Geographically-weighted regression of knowledge and behaviour determinants to
      anti-malarial recommending and dispensing practice among medicine retailers in
      western Kenya: capacitating targeted interventions.
AB  - BACKGROUND: Most patients with malaria seek treatment first in retail drug shops.
      Myriad studies have examined retailer behaviours and characteristics to
      understand the determinants to these behaviours. Geospatial methods are helpful
      in discovering if geographic location plays a role in the relationship between
      determinants and outcomes. This study aimed to discover if spatial
      autocorrelation exists in the relationship between determinants and retailer
      behaviours, and to provide specific geographic locations and target behaviours
      for tailoring future interventions. METHODS: Retailer behaviours and
      characteristics captured from a survey deployed to medicine retailers in the
      Webuye Demographic and Health Surveillance Site were analysed using geographic
      weighted regression to create prediction models for three separate outcomes:
      recommending the first-line anti-malarial therapy to adults, recommending the
      first-line anti-malarial therapy to children, and selling that therapy more than
      other anti-malarials. The estimated regression coefficients for each determinant,
      as well as the pseudo R2 values for each final model, were then mapped to assess
      spatial variability and local areas of best model fit. RESULTS: The relationships
      explored were found to be non-stationary, indicating that spatial heterogeneity
      exist in the data. The association between having a pharmacy-related health
      training and recommending the first-line anti-malarial treatment to adults was
      strongest around the peri-urban centre: comparing those with training in pharmacy
      to those without training (OR = 5.75, p = 0.021). The association between knowing
      the first-line anti-malarial and recommending it to children was strongest in the
      north of the study area compared to those who did not know the MOH-recommended
      anti-malarial (OR = 2.34, p = 0.070). This is also the area with the strongest
      association between attending a malaria workshop and selling the MOH-recommended
      anti-malarial more than other anti-malarials, compared to retailers who did not
      attend a workshop (OR = 2.38, p = 0.055). CONCLUSION: Evidence suggests that
      spatial heterogeneity exists in these data, indicating that the relationship
      between determinants and behaviours varies across space. This is valuable
      information for intervention design, allowing efforts to focus on those factors
      that have the strongest relationship with their targeted behaviour within that
      geographic space, increasing programme efficiency and cost-effectiveness.

PMID- 27871305
TI  - Response to a trial on reversal of Death by Neurologic Criteria.

PMID- 27871304
TI  - Respiratory viral infections and host responses; insights from genomics.
AB  - Respiratory viral infections are a leading cause of disease and mortality. The
      severity of these illnesses can vary markedly from mild or asymptomatic upper
      airway infections to severe wheezing, bronchiolitis or pneumonia. In this
      article, we review the viral sensing pathways and organizing principles that
      govern the innate immune response to infection. Then, we reconstruct the
      molecular networks that differentiate symptomatic from asymptomatic respiratory
      viral infections, and identify the underlying molecular drivers of these
      networks. Finally, we discuss unique aspects of the biology and pathogenesis of
      infections with respiratory syncytial virus, rhinovirus and influenza, drawing on
      insights from genomics.

PMID- 27871307
TI  - Current models of care for disorders of sex development - results from an
      International survey of specialist centres.
AB  - BACKGROUND: To explore the current models of practice in centres delivering
      specialist care for children with disorders of sex development (DSD), an
      international survey of 124 clinicians, identified through DSDnet and the I-DSD
      Registry, was performed in the last quarter of 2014. RESULTS: A total of 78 (63
      %) clinicians, in 75 centres, from 38 countries responded to the survey. A formal
      national network for managing DSD was reported to exist in 12 (32 %) countries.
      The paediatric specialists routinely involved in the initial evaluation of a
      newborn included: endocrinologist (99 %), surgeon/urologist (95 %), radiologist
      (93 %), neonatologist (91 %), clinical geneticist (81 %) and clinical
      psychologist (69 %). A team consisting of paediatric specialists in
      endocrinology, surgery/urology, clinical psychology, and nursing was only
      possible in 31 (41 %) centres. Of the 75 centres, 26 (35 %) kept only a local DSD
      registry and 40 (53 %) shared their data in a multicentre DSD registry.
      Attendance in local, national and international DSD-related educational programs
      was reported by 69, 78 and 84 % clinicians, respectively. Participation in
      audits/quality improvement exercises in DSD care was reported by 14 (19 %)
      centres. In addition to complex biochemistry and molecular genetic
      investigations, 40 clinicians (51 %) also had access to next generation
      sequencing. A genetic test was reported to be more preferable than biochemical
      tests for diagnosing 5-alpha reductase deficiency and 17-beta hydroxysteroid
      dehydrogenase 3 deficiency by 50 and 55 % clinicians, respectively. CONCLUSION:
      DSD centres report a high level of interaction at an international level, have
      access to specialist staff and are increasingly relying on molecular genetics for
      routine diagnostics. The quality of care provided by these centres locally
      requires further exploration.

PMID- 27871306
TI  - Akirin2 is essential for the formation of the cerebral cortex.
AB  - BACKGROUND: The proper spatial and temporal regulation of dorsal telencephalic
      progenitor behavior is a prerequisite for the formation of the highly-organized,
      six-layered cerebral cortex. Premature differentiation of cells, disruption of
      cell cycle timing, excessive apoptosis, and/or incorrect neuronal migration
      signals can have devastating effects, resulting in a number of neurodevelopmental
      disorders involving microcephaly and/or lissencephaly. Though genes encoding many
      key players in cortical development have been identified, our understanding
      remains incomplete. We show that the gene encoding Akirin2, a small nuclear
      protein, is expressed in the embryonic telencephalon. Converging evidence
      indicates that Akirin2 acts as a bridge between transcription factors (including
      Twist and NF-kappaB proteins) and the BAF (SWI/SNF) chromatin remodeling
      machinery to regulate patterns of gene expression. Constitutive knockout of
      Akirin2 is early embryonic lethal in mice, while restricted loss in B cells led
      to disrupted proliferation and cell survival. METHODS: We generated cortex
      restricted Akirin2 knockouts by crossing mice harboring a floxed Akirin2 allele
      with the Emx1-Cre transgenic line and assessed the resulting embryos using in
      situ hybridization, EdU labeling, and immunohistochemistry. RESULTS: The vast
      majority of Akirin2 mutants do not survive past birth, and exhibit extreme
      microcephaly, with little dorsal telencephalic tissue and no recognizable cortex.
      This is primarily due to massive cell death of early cortical progenitors, which
      begins at embryonic day (E)10, shortly after Emx1-Cre is active. Immunostaining
      and cell cycle analysis using EdU labeling indicate that Akirin2-null progenitors
      fail to proliferate normally, produce fewer neurons, and undergo extensive
      apoptosis. All of the neurons that are generated in Akirin2 mutants also undergo
      apoptosis by E12. In situ hybridization for Wnt3a and Wnt-responsive genes
      suggest defective formation and/or function of the cortical hem in Akirin2 null
      mice. Furthermore, the apical ventricular surface becomes disrupted, and Sox2
      positive progenitors are found to "spill" into the lateral ventricle.
      CONCLUSIONS: Our data demonstrate a previously-unsuspected role for Akirin2 in
      early cortical development and, given its known nuclear roles, suggest that it
      may act to regulate gene expression patterns critical for early progenitor cell
      behavior and cortical neuron production.

PMID- 27871308
TI  - Recruiting to Clinical Trials on the Telephone - a randomized controlled trial.
AB  - BACKGROUND: Informed consent is an essential element of clinical research.
      Obtaining consent, however, may be challenging. The use of the telephone for
      giving information and obtaining consent may be practical but little formal
      research has been done. METHODS: We examined the use of the telephone for the
      purpose of informing expectant mothers about The Danish Calmette Study; a
      randomized clinical trial assessing neonatal Bacille Calmette-Guerin vaccination.
      Expectant mothers received an invitation letter with a Participant Information
      Sheet about The Danish Calmette Study, the present trial, and a Consent Form. Two
      to 4 weeks later we contacted the mothers to discuss potential participation in
      the present trial. At this initial telephone contact, and after consent from the
      mothers, we randomized expectant mothers to receive the verbal information about
      The Danish Calmette Study by telephone, or at a face-to-face consultation. The
      primary outcome was a communication score, consisting of comprehension of
      information about The Danish Calmette Study and satisfaction with the information
      process. The outcome was measured using a questionnaire 2 days after the
      information was provided, and 2.5 months after the birth of the child. RESULTS:
      The communication score obtained 2 days after information was given was
      significantly reduced in the telephone group, effect size -0.74 (95% confidence
      interval (CI), -1.11 to -0.36). The effect sizes of the subscores were -0.87 (95%
      CI, -1.25 to -0.49) for satisfaction and -0.22 (95% CI, -0.58 to 0.14) for
      comprehension. The effect sizes were slightly reduced when assessed 2.5 months
      after the birth. CONCLUSION: The communication score was reduced in the telephone
      group. This was due to a reduction in satisfaction, while no difference in the
      comprehension could be found in comparison to the control group. This may be
      ethically acceptable as both groups had high satisfaction scores. TRIAL
      REGISTRATION: ClinicalTrials.gov, registered on 5 October 2015 with trial
      registration number NCT02570061 .

PMID- 27871309
TI  - Draft genome of the living fossil Ginkgo biloba.
AB  - BACKGROUND: Ginkgo biloba L. (Ginkgoaceae) is one of the most distinctive plants.
      It possesses a suite of fascinating characteristics including a large genome,
      outstanding resistance/tolerance to abiotic and biotic stresses, and dioecious
      reproduction, making it an ideal model species for biological studies. However,
      the lack of a high-quality genome sequence has been an impediment to our
      understanding of its biology and evolution. FINDINGS: The 10.61 Gb genome
      sequence containing 41,840 annotated genes was assembled in the present study.
      Repetitive sequences account for 76.58% of the assembled sequence, and long
      terminal repeat retrotransposons (LTR-RTs) are particularly prevalent. The
      diversity and abundance of LTR-RTs is due to their gradual accumulation and a
      remarkable amplification between 16 and 24 million years ago, and they contribute
      to the long introns and large genome. Whole genome duplication (WGD) may have
      occurred twice, with an ancient WGD consistent with that shown to occur in other
      seed plants, and a more recent event specific to ginkgo. Abundant gene clusters
      from tandem duplication were also evident, and enrichment of expanded gene
      families indicates a remarkable array of chemical and antibacterial defense
      pathways. CONCLUSIONS: The ginkgo genome consists mainly of LTR-RTs resulting
      from ancient gradual accumulation and two WGD events. The multiple defense
      mechanisms underlying the characteristic resilience of ginkgo are fostered by a
      remarkable enrichment in ancient duplicated and ginkgo-specific gene clusters.
      The present study sheds light on sequencing large genomes, and opens an avenue
      for further genetic and evolutionary research.

PMID- 27871311
TI  - Erratum to: JMJD2A contributes to breast cancer progression through
      transcriptional repression of the tumor suppressor ARHI.

PMID- 27871312
TI  - Increased frequency of porcine epidemic diarrhea virus shedding and lesions in
      suckling pigs compared to nursery pigs and protective immunity in nursery pigs
      after homologous re-challenge.
AB  - Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs and spreads
      rapidly after entering naive pig populations. The objectives were to (1) compare
      the disease course following inoculation with PEDV isolate US/Colorado/2013 in
      naive 10 day and 8 week-old pigs, and (2) contrast the naive response to
      homologous challenge in 8 week-old pigs. Pigs were randomly assigned into group 1
      (n = 40, no PEDV exposure), group 2 (n = 43, PEDV inoculation at 10 days of age)
      and group 3 (n = 48, PEDV inoculation at 8 weeks of age). Thirty-three group 2
      pigs received a homologous challenge at 8 weeks of age. Following primary or
      secondary inoculation, 3-10 pigs were euthanized at days post-inoculation (dpi)
      1, 2, 3, 7 or 14. Clinical signs were more pronounced in 10 day-old pigs compared
      to 8 week-old pigs at dpi 2 and 3, a higher number of 10 day-old pigs shed PEDV
      RNA in feces compared to 8 week-old pigs. Typical severe atrophic enteritis of
      PEDV infection was observed at dpi 3 in both age groups, and at dpi 4 and 14
      fecal shedding patterns were also similar. While both age groups had
      seroconverted to PEDV by dpi 14, IgG levels were higher in 8 week-old pigs. PEDV
      IgA antibodies were detected in feces of approximately 50% of the pigs at dpi 44.
      In homologous challenged pigs, no clinical signs or lesions were found, and PEDV
      fecal shedding was restricted to less than 10% of the pigs indicating the
      existence of homologous protection 44 days after initial PEDV exposure.

PMID- 27871310
TI  - Transcriptome analysis reveals manifold mechanisms of cyst development in ADPKD.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) causes
      progressive loss of renal function in adults as a consequence of the accumulation
      of cysts. ADPKD is the most common genetic cause of end-stage renal disease.
      Mutations in polycystin-1 occur in 87% of cases of ADPKD and mutations in
      polycystin-2 are found in 12% of ADPKD patients. The complexity of ADPKD has
      hampered efforts to identify the mechanisms underlying its pathogenesis. No
      current FDA (Federal Drug Administration)-approved therapies ameliorate ADPKD
      progression. RESULTS: We used the de Almeida laboratory's sensitive new
      transcriptogram method for whole-genome gene expression data analysis to analyze
      microarray data from cell lines developed from cell isolates of normal kidney and
      of both non-cystic nephrons and cysts from the kidney of a patient with ADPKD. We
      compared results obtained using standard Ingenuity Volcano plot analysis, Gene
      Set Enrichment Analysis (GSEA) and transcriptogram analysis. Transcriptogram
      analysis confirmed the findings of Ingenuity, GSEA, and published analysis of
      ADPKD kidney data and also identified multiple new expression changes in KEGG
      (Kyoto Encyclopedia of Genes and Genomes) pathways related to cell growth, cell
      death, genetic information processing, nucleotide metabolism, signal
      transduction, immune response, response to stimulus, cellular processes, ion
      homeostasis and transport and cofactors, vitamins, amino acids, energy,
      carbohydrates, drugs, lipids, and glycans. Transcriptogram analysis also provides
      significance metrics which allow us to prioritize further study of these
      pathways. CONCLUSIONS: Transcriptogram analysis identifies novel pathways altered
      in ADPKD, providing new avenues to identify both ADPKD's mechanisms of
      pathogenesis and pharmaceutical targets to ameliorate the progression of the
      disease.

PMID- 27871313
TI  - Conservation of immune gene signatures in solid tumors and prognostic
      implications.
AB  - BACKGROUND: Tumor-infiltrating leukocytes can either limit cancer growth or
      facilitate its spread. Diagnostic strategies that comprehensively assess the
      functional complexity of tumor immune infiltrates could have wide-reaching
      clinical value. In previous work we identified distinct immune gene signatures in
      breast tumors that reflect the relative abundance of infiltrating immune cells
      and exhibited significant associations with patient outcomes. Here we
      hypothesized that immune gene signatures agnostic to tumor type can be identified
      by de novo discovery of gene clusters enriched for immunological functions and
      possessing internal correlation structure conserved across solid tumors from
      different anatomic sites. METHODS: We assembled microarray expression datasets
      encompassing 5,295 tumors of the breast, colon, lung, ovarian and prostate.
      Unsupervised clustering methods were used to determine number and composition of
      gene clusters within each dataset. Immune-enriched gene clusters (signatures)
      identified by gene ontology enrichment were analyzed for internal correlation
      structure and conservation across tumors then compared against expression
      profiles of: 1) flow-sorted leukocytes from peripheral blood and 2) >300 cancer
      cell lines from solid and hematologic cancers. Cox regression analysis was used
      to identify signatures with significant associations with clinical outcome.
      RESULTS: We identified nine distinct immune-enriched gene signatures conserved
      across all five tumor types. The signatures differentiated specific leukocyte
      lineages with moderate discernment overall, and naturally organized into six
      discrete groups indicative of admixed lineages. Moreover, seven of the signatures
      exhibit minimal and uncorrelated expression in cancer cell lines, suggesting that
      these signatures derive predominantly from infiltrating immune cells. All nine
      immune signatures achieved statistically significant associations with patient
      prognosis (p<0.05) in one or more tumor types with greatest significance observed
      in breast and skin cancers. Several signatures indicative of myeloid lineages
      exhibited poor outcome associations that were most apparent in brain and colon
      cancers. CONCLUSIONS: These findings suggest that tumor infiltrating immune cells
      can be differentiated by immune-specific gene expression patterns that quantify
      the relative abundance of multiple immune infiltrates across a range of solid
      tumor types. That these markers of immune involvement are significantly
      associated with patient prognosis in diverse cancers suggests their clinical
      utility as pan-cancer markers of tumor behavior and immune responsiveness.

PMID- 27871314
TI  - A mixed-methods systematic review protocol to examine the use of physical
      restraint with critically ill adults and strategies for minimizing their use.
AB  - BACKGROUND: Critically ill patients frequently experience severe agitation
      placing them at risk of harm. Physical restraint is common in intensive care
      units (ICUs) for clinician concerns about safety. However, physical restraint may
      not prevent medical device removal and has been associated with negative physical
      and psychological consequences. While professional society guidelines,
      legislation, and accreditation standards recommend physical restraint
      minimization, guidelines for critically ill patients are over a decade old, with
      recommendations that are non-specific. Our systematic review will synthesize
      evidence on physical restraint in critically ill adults with the primary
      objective of identifying effective minimization strategies. METHODS: Two authors
      will independently search from inception to July 2016 the following: Ovid
      MEDLINE, CINAHL, Embase, Web of Science, Cochrane Library, PROSPERO, Joanna
      Briggs Institute, grey literature, professional society websites, and the
      International Clinical Trials Registry Platform. We will include quantitative and
      qualitative study designs, clinical practice guidelines, policy documents, and
      professional society recommendations relevant to physical restraint of critically
      ill adults. Authors will independently perform data extraction in duplicate and
      complete risk of bias and quality assessment using recommended tools. We will
      assess evidence quality for quantitative studies using the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) approach and for
      qualitative studies using the Confidence in the Evidence from Reviews of
      Qualitative Research (CERQual) guidelines. Outcomes of interest include (1)
      efficacy/effectiveness of physical restraint minimization strategies; (2) adverse
      events (unintentional device removal, psychological impact, physical injury) and
      associated benefits including harm prevention; (3) ICU outcomes (ventilation
      duration, length of stay, and mortality); (4) prevalence, incidence, patterns of
      use including patient and treatment characteristics and chemical restraint; (5)
      barriers and facilitators to minimization; (6) patient, family, and healthcare
      professional perspectives; (7) professional society-endorsed recommendations; and
      (8) evidence gaps and research priorities. DISCUSSION: We will use our systematic
      review findings to produce updated guidelines on physical restraint use for
      critically ill adults and to develop a professional society-endorsed position
      statement. This will foster patient and clinician safety by providing clinicians,
      administrators, and policy makers with a tool to promote minimal and safe use of
      physical restraint for critically ill adults. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42015027860.

PMID- 27871315
TI  - Management of uterine rupture: a case report and review of the literature.
AB  - BACKGROUND: Maternal morbidity and mortality has been a major World Health
      Organization concern over the years, especially in sub-Saharan Africa. This paper
      reports uterine rupture with severe hypovolemic shock managed at the Douala
      General Hospital, Cameroon. Early clinical diagnosis is paramount to maternal
      survival. CASE PRESENTATION: Mrs. MM aged 25 years, G3P2012, of the Bamileke
      tribe in Cameroon was admitted to our Department in hypovolemic shock BP = 70/40
      mmHg, pulse 120 beats per minute, with altered consciousness (Glasgow Coma Scale
      = 13). She has a history of missed abortion at 19 weeks gestation and an attempt
      to evacuate the uterus with misoprostol that led to uterine rupture. She
      underwent a total abdominal hysterectomy and blood transfusion. Her post
      operative stay in hospital was uneventful. CONCLUSION: Uterine rupture is a
      complication that can be eliminated under conditions of best obstetric practice.
      To attain this objective, use of misoprostol in primary health facilities should
      be stopped or proper management of the medication instituted. The survival of
      patients after uterine rupture depends on the time interval between rupture and
      intervention, and the availability of blood products for transfusion.

PMID- 27871317
TI  - Heterotopic ossification following anti-NMDA receptor encephalitis: a case
      report.
AB  - BACKGROUND: Heterotopic ossification (HO) is defined as the formation of true
      bone tissue in non-osseous tissues. HO may occur under several conditions such as
      soft tissue injury, central nervous system injury and many other diseases like
      arthopathies, and vasculopathies. The underlying mechanisms of HO are not well
      elucidated. Anti-NMDA receptor encephalitis is a newly recognized autoimmune
      mediated disease which is predominant in young female patients with ovarian
      teratomas. Encephalitis complicated with HO has rarely been reported. CASE
      PRESENTATION: Here we report a case of anti-NMDA receptor encephalitis with
      severe muscle ossifications. A 15 years old female patient presented with fever,
      changed mental status of confusion, rigidity of the arms and legs, and oral
      facial dyskinesias. Diagnosis of anti-NMDA receptor encephalitis was confirmed by
      detection of anti-NMDA receptor antibodies both in serum and CSF. Due to the
      severity of the disease, 3-weeks' intensive care and mechanical ventilation were
      administrated for the patient. Image of pelvic CT and MRI of the patient showed
      dynamic changing process of HO. The muscles showed edema and scattered
      inflammation at the very beginning, and then gradually formed mature bone tissue.
      CONCLUSIONS: Anti-NMDA receptor encephalitis often presents with severe
      neurologic symptoms and requires long time intensive care and mechanical
      ventilation, which makes the patient easily complicate with HO. More studies are
      required to elucidate the mechanisms of HO and more attention should be paid to
      patients with encephalitis who might develop severe muscle ossifications
      requiring early interventions.

PMID- 27871316
TI  - Heterogeneous antigenic properties of the porcine reproductive and respiratory
      syndrome virus nucleocapsid.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus
      responsible for a widespread contagious disease of domestic pigs with high
      economic impact. Switzerland is one of the rare PRRSV-free countries in Europe,
      although sporadic outbreaks have occurred in the past. The PRRSV isolate IVI-1173
      from the short outbreak in Switzerland in 2012 was entirely sequenced, and a
      functional full-length cDNA clone was constructed. Genetic and antigenic
      characterization of IVI-1173 revealed the importance of amino acid 90 of the
      nucleocapsid protein N as part of a conformational epitope. IVI-1173 was not
      detected by SDOW17, a monoclonal antibody against N widely used to detect PRRSV
      infected cells. Substitution of alanine at position 90 of N [N(A90)] with a
      threonine [N(T90)] restored reactivity of vIVI1173-N(T90) to SDOW17 completely.
      The relevance of this amino acid for the conformational SDOW17 epitope of PRRSV N
      was further confirmed by the opposite substitution in a functional cDNA clone of
      the genotype 2 isolate RVB-581. Finally, N proteins from ten genotype 1 strains
      differing from threonine at position 90 were analysed for reactivity with SDOW17.
      N(A90) totally disrupted or severely affected the epitope in 7 out of 8 strains
      tested. Based on these findings, 225 genotype 1 strains were screened for the
      prevalence of N(A90). N(A90) is rare in classical subtype 1 and in subtype 3
      strains, but is frequent in Russian subtype 1 (70%) and in subtype 2 (45%)
      isolates. In conclusion, this study highlights the variable antigenic properties
      of N among genotype 1 PRRSV strains.

PMID- 27871318
TI  - Reference curves of birth weight, length, and head circumference for gestational
      ages in Yogyakarta, Indonesia.
AB  - BACKGROUND: The birth weight reference curve to estimate the newborns at risk in
      need of assessment and monitoring has been established. The previous reference
      curves from Indonesia, approximately 8 years ago, were based on the data
      collected from teaching hospitals only with limited gestational ages. The aims of
      the study were to update the reference curves for birth weight, supine length and
      head circumference for Indonesia, and to compare birth weight curves of boys and
      girls, first child and later children, and the ones in the previous studies.
      METHODS: Data were extracted from the Maternal-Perinatal database between 1998
      2007. Only live singletons with recorded gestational ages of 26 to 42 weeks and
      the exact time of admission to the neonatal facilities delivered or referred
      within 24 h of age to Sardjito Hospital, five district hospitals and five health
      centers in Yogyakarta Special Territory were included. Newborns with severely ill
      conditions, congenital anomaly and chromosomal abnormality were excluded.
      Smoothening of the curves was accomplished using a third-order polynomial
      equation. RESULTS: Our study included 54,599 singleton live births. Growth curves
      were constructed for boys (53.3%) and girls (46.7%) for birth weight, supine
      length, and head circumference. At term, mean birth weight for each gestational
      age of boys was significantly higher than that of girls. While mean birth weight
      for each gestational age of first-born-children, on the other hand was
      significantly lower than that of later-born-children. The mean birth weight was
      lower than that of Lubchenco's study. Compared with the previous Indonesian study
      by Alisyahbana, no differences were observed for the aterm infants, but lower
      mean birth weight was observed in preterm infants. CONCLUSIONS: Updated neonatal
      reference curves for birth weight, supine length and head circumference are
      important to classify high risk newborns in specific area and to identify
      newborns requiring attention.

PMID- 27871319
TI  - A phase I dose-escalation study of PEP02 (irinotecan liposome injection) in
      combination with 5-fluorouracil and leucovorin in advanced solid tumors.
AB  - BACKGROUND: PEP02 (also known as MM-398, nal-IRI) is a novel nanoparticle
      formulation of irinotecan encapsulated in liposomes. The aims of this study were
      to investigate the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and
      pharmacokinetics (PK) of PEP02 in combination with 5-FU and LV, in patients with
      advanced refractory solid tumors. METHODS: Patients were enrolled in cohorts to
      receive PEP02 from 60 to 120 mg/m2 (dose expressed as the irinotecan
      hydrochloride trihydrate salt) as a 90-min intravenous infusion on day 1,
      followed by 24 h infusion of 5-FU 2,000 mg/m2 and LV 200 mg/m2 on days 1 and 8,
      every 3 weeks. RESULTS: A total of 16 patients were assigned to four dose levels,
      60 (three patients), 80 (six patients), 100 (five patients) and 120 mg/m2 (two
      patients). DLT was observed in four patients, two at the 100 mg/m2 dose level
      (one had grade III infection with hypotension and grade III hemorrhage; the other
      had grade III diarrhea and grade IV neutropenia), and two at the 120 mg/m2 dose
      level (one had grade III diarrhea and grade IV neutropenia; the other had grade
      III diarrhea). The MTD of PEP02 was determined as 80 mg/m2. The most common
      treatment-related adverse events were nausea (81%), diarrhea (75%) and vomiting
      (69%). Among the six patients who received the MTD, one patient exhibited partial
      response, four patients had stable disease and one showed progressive disease.
      Pharmacokinetic data showed that PEP02 had a lower peak plasma concentration,
      longer half-life, and increased area under the plasma concentration-time curve
      from zero to time t of SN-38 than irinotecan at similar dose level. CONCLUSIONS:
      The MTD of PEP02 on day 1 in combination with 24-h infusion of 5-FU and LV on
      days 1 and 8, every 3 weeks was 80 mg/m2, which will be the recommended dose for
      future studies. TRIAL REGISTRATION: The trial was retrospectively registered (
      NCT02884128 ) with date of registration: August 12, 2016.

PMID- 27871320
TI  - Assessment of the dimensionality of the Wijma delivery expectancy/experience
      questionnaire using factor analysis and Rasch analysis.
AB  - BACKGROUND: Fear of childbirth has negative consequences for a woman's physical
      and emotional wellbeing. The most commonly used measurement tool for childbirth
      fear is the Wijma Delivery Expectancy Questionnaire (WDEQ-A). Although originally
      conceptualized as unidimensional, subsequent investigations have suggested it is
      multidimensional. This study aimed to undertake a detailed psychometric
      assessment of the WDEQ-A; exploring the dimensionality and identifying possible
      subscales that may have clinical and research utility. METHODS: WDEQ-A was
      administered to a sample of 1410 Australian women in mid-pregnancy. The
      dimensionality of WDEQ-A was explored using exploratory (EFA) and confirmatory
      factor analysis (CFA), and Rasch analysis. RESULTS: EFA identified a four factor
      solution. CFA failed to support the unidimensional structure of the original WDEQ
      A, but confirmed the four factor solution identified by EFA. Rasch analysis was
      used to refine the four subscales (Negative emotions: five items; Lack of
      positive emotions: five items; Social isolation: four items; Moment of birth:
      three items). Each WDEQ-A Revised subscale showed good fit to the Rasch model and
      adequate internal consistency reliability. The correlation between Negative
      emotions and Lack of positive emotions was strong, however Moment of birth and
      Social isolation showed much lower intercorrelations, suggesting they should not
      be added to create a total score. CONCLUSION: This study supports the findings of
      other investigations that suggest the WDEQ-A is multidimensional and should not
      be used in its original form. The WDEQ-A Revised may provide researchers with a
      more refined, psychometrically sound tool to explore the differential impact of
      aspects of childbirth fear.

PMID- 27871321
TI  - Biochemical characterization and synergism of cellulolytic enzyme system from
      Chaetomium globosum on rice straw saccharification.
AB  - BACKGROUND: Efficient hydrolysis of lignocellulosic materials to sugars for
      conversion to biofuels and chemicals is a key step in biorefinery. Designing an
      active saccharifying enzyme system with synergy among their components is
      considered a promising approach. RESULTS: In this study, a lignocellulose
      degrading enzyme system of Chaetomium globosum BCC5776 (CG-Cel) was characterized
      for its activity and proteomic profiles, and synergism with accessory enzymes.
      The highest cellulase productivity of 0.40 FPU/mL was found for CG-Cel under the
      optimized submerged fermentation conditions on 1% (w/v) EPFB (empty palm fruit
      bunch), 2% microcrystalline cellulose (Avicel(r)) and 1% soybean meal (SBM) at 30
      degrees C, pH 5.8 for 6 d. CG-Cel worked optimally at 50-60  degrees C in an
      acidic pH range. Proteomics analysis by LC/MS/MS revealed a complex enzyme system
      composed of core cellulases and accessory hydrolytic/non-hydrolytic enzymes
      attacking plant biopolymers. A synergistic enzyme system comprising the CG-Cel, a
      beta-glucosidase (Novozyme(r) 188) and a hemicellulase Accellerase(r) XY was
      optimized on saccharification of alkaline-pretreated rice straw by a mixture
      design approach. Applying a full cubic model, the optimal ratio of ternary enzyme
      mixture containing CG-Cel: Novozyme(r) 188: Accellerase(r) XY of 44.4:20.6:35.0
      showed synergistic enhancement on reducing sugar yield with a glucose releasing
      efficiency of 256.4 mg/FPU, equivalent to a 2.9 times compared with that from CG
      Cel alone. CONCLUSIONS: The work showed an approach for developing an active
      synergistic enzyme system based on the newly characterized C. globosum for
      lignocellulose saccharification and modification in bio-industries.

PMID- 27871322
TI  - Causes of maternal and child mortality among Cambodian sex workers and their
      children: a cross sectional study.
AB  - BACKGROUND: To reach global and national goals for maternal and child mortality,
      countries must identify vulnerable populations, which includes sex workers and
      their children. The objective of this study was to identify and describe maternal
      deaths of female sex workers in Cambodia and causes of death among their
      children. METHODS: A convenience sample of female sex workers were recruited by
      local NGOs that provide support to sex workers. We modified the maternal
      mortality section of the 2010 Cambodia Demographic and Health Survey and
      collected reports of all deaths of female sex workers. For each death we ask the
      'sisterhood' methodology questions to identify maternal deaths. For child deaths
      we asked each mother who reported the death of a child about the cause of death.
      We also asked all participants about the cause of deaths of children of other
      female sex workers. RESULTS: We interviewed 271 female sex workers in the four
      largest Cambodian cities between May and September 2013. Participants reported 32
      deaths of other female sex workers that met criteria for maternal death. The most
      common reported causes of maternal deaths were abortion (n = 13;40%) and HIV (n =
      5;16%). Participants report deaths of 8 of their children and 50 deaths of
      children of other female sex workers. HIV was the reported cause of death for 13
      (36%) children under age five. CONCLUSION: This is the first report of maternal
      deaths of sex workers in Cambodia or any other country. This modification of the
      sisterhood methodology has not been validated and did not allow us to calculate
      maternal mortality rates so the results are not generalizable, however these
      deaths may represent unrecognized maternal deaths in Cambodia. The results also
      indicate that children of sex workers in Cambodia are at risk of HIV and may not
      be accessing treatment. These issues require additional studies but in the
      meantime we must assure that sex workers in Cambodia and their children have
      access to quality health services.

PMID- 27871323
TI  - Spine surgery outcome in patients who sought compensation after a motor vehicle
      accident: a retrospective cohort study.
AB  - BACKGROUND: Back and neck pain are common after road traffic injury and are
      treated by spine surgery in some cases. This study aimed to describe the outcomes
      of spine surgery in people who made an insurance claim after road traffic
      accidents without an associated spinal fracture or dislocation. METHODS: This
      study was a retrospective cohort based on insurers' data of Compulsory Third
      Party (CTP) claims. File audit and data extraction were undertaken using a study
      specific proforma. Primary outcomes were ongoing pain and symptoms,
      complications, return to work and pre-injury duties, and ongoing treatment 2
      years following spine surgery. Secondary outcomes were health care costs based on
      data provided by the insurers. RESULTS: After screening 766 files, 90 cases were
      included (female: 48; mean age: 46 years). Among the subjects who were working
      prior the injury, the rate of return to work was 37% and return to pre-injury
      duties was 23% 2 years following the surgery. The average number of appointments
      with health care professionals in the 1 year after surgery was 21, compared to 10
      for the 1 year prior to surgery (p = 0.03). At 2 years following the initial
      surgery, 21% of claimants had undergone revision spine surgery; 68% reported
      ongoing back pain and 41% had ongoing radicular symptoms. The difference between
      costs 1 year before and after surgery (excluding surgical costs) was
      statistically significant (p = 0.04). Fusions surgery was associated with higher
      total costs than decompression alone. After adjusting for surgery type, lumbar
      surgery was associated with higher costs in the 1 year after surgery and total
      surgical costs compared to cervical surgery. CONCLUSIONS: The majority of
      claimants continued having clinical symptoms, continued using health care and did
      not return to work despite undertaking spine surgery.

PMID- 27871324
TI  - Factors affecting the delivery of community pharmacist-led medication reviews:
      evidence from the MedsCheck annual service in Ontario.
AB  - BACKGROUND: Medication reviews have become part of pharmacy practice across
      developed countries. This study aimed to identify factors affecting the
      likelihood of eligible Ontario seniors receiving a pharmacy-led medication review
      called MedsCheck annual (MCA). METHODS: We designed a cohort study using a random
      sample of pharmacy claims for MCA-eligible Ontario seniors using linked
      administrative data from April 2012 to March 2013. Guided by a conceptual
      framework, we constructed a generalized-estimating-equations model to estimate
      the effect of patient, pharmacy and community factors on the likelihood of
      receiving MCA. RESULTS: Of the 2,878,958 eligible claim-dates, 65,605 included an
      MCA. Compared to eligible individuals who did not receive an MCA, recipients were
      more likely to have a prior MCA (OR = 3.03), receive a new medication on the
      claim-date (OR = 1.78), be hypertensive (OR = 1.18) or have a recent
      hospitalization (OR = 1.07). MCA recipients had fewer medications (e.g., OR =
      0.44 for >=12 medications versus 0-4 medications), and were less likely to
      receive an MCA in a rural (OR = 0.74) or high-volume pharmacy (OR = 0.65).
      CONCLUSIONS: The most important determinant of receiving an MCA was having had a
      prior MCA. Overall, MCA recipients were healthier, younger, urban-dwelling, and
      taking fewer medications than non-recipients. Policies regarding current and
      future medication review programs may need to evolve to ensure that those at
      greatest need receive timely and comprehensive medication reviews.

PMID- 27871325
TI  - Impact of placental Plasmodium falciparum malaria infection on the Cameroonian
      maternal and neonate's plasma levels of some cytokines known to regulate T cells
      differentiation and function.
AB  - BACKGROUND: The impact of placental malaria (PM) infection on the expression
      profile of some cytokines known to regulate T cell differentiation and function
      and their influence on birth weight remain unclear. Moreover, there are no
      reports showing the relationship between PM and IL-27 or IL-28A. This study
      therefore sought to investigate whether placental P. falciparum infection alters
      the expression profile of the cytokines IL-28A, IL-27, IL-17E and IL-6 in mothers
      and their new born. METHODS: In a cross-sectional study conducted between 2013
      and 2015 in Yaounde, Cameroon, peripheral, placental and cord blood samples were
      collected from 108 women at delivery. Parasitaemia was determined microscopically
      and haemoglobin levels determined using a Coulter counter. Plasma levels of
      cytokines (IL-28A, IL-27, IL-17E and IL-6) were measured by Luminex magnetic
      screening assay. RESULTS: Malaria parasite density in placenta impression smear
      associated negatively with maternal haemoglobin level (P < 0.0001) and baby birth
      weight (P = 0.016). While IL-17E, IL-27 and IL-28A levels were significantly
      higher in placental and cord plasma than in peripheral (P < 0.0001, < 0.001 and P
      = 0.026, respectively), an opposite relationship was observed with IL-6 (P =
      0.0018). Multivariate analysis confirmed results of univariate analysis where the
      presence of malaria parasites or pigments in placenta tissue impression smears
      correlated with decrease levels of maternal IL-17E, IL-27 and IL-28A and neonate
      levels of IL-28A and IL-17E (0.0001 <= P <= 0.02). Placental and peripheral
      parasitaemias also correlated positively with peripheral plasma levels of IL-6
      (rs = 0.18, P = 0.05 and rs = 0.17, P = 0.07, respectively). In addition, high
      maternal haemoglobin level associated with increasing levels of IL-17E, IL-27 and
      IL-28A in peripheral plasma (0.002 <= P <= 0.018) and high placental and cord
      plasma levels of these cytokines associated with increasing birth weight (0.0001
      <= P <= 0.0027). CONCLUSIONS: Placental malaria downregulates maternal plasma
      levels of IL-17E, IL-27 and IL-28A and neonates' plasma levels of IL-17E and IL
      28A cytokines, which could help for parasite clearance and increase child birth
      weight. The study is expected to provide leads that should help identify
      potential biomarkers for improved birth weight and therapeutic interventions.

PMID- 27871327
TI  - Ebola, Zika and the International Health Regulations - implications for Port
      Health Preparedness.
AB  - BACKGROUND: The outbreak of Ebola Virus Disease in West Africa in 2014-2015 was
      unprecedented in terms of its scale and consequence.  This, together with the
      emergence of Zika virus as a Public Health Emergency of International Concern in
      2016, has again highlighted the potential for disease to spread across
      international borders and provided an impetus for countries to review their Port
      Health preparedness. This report reviews the legislative framework and actions
      taken under this framework in advancing and improving Port Health preparedness in
      Ireland, in response to the declaration of the Public Health Emergency of
      International Concern for Ebola Virus Disease in August 2014. FINDINGS:
      Infectious disease Shipping and Aircraft Regulations were brought into force in
      Ireland in 2008 and 2009, respectively. Preparatory actions taken under these and
      the International Health Regulations necessitated significant levels of cross
      disciplinary working with other organisations, both within and beyond traditional
      healthcare settings. Information packs on Ebola Virus Disease were prepared and
      distributed to airports, airlines, port authorities and shipping agents, and
      practical exercises were held at relevant sites. Agreements were put in place for
      contact tracing of passenger and crew on affected conveyances and protocols were
      established for the management of Medical Declarations of Health from ships
      coming from West Africa. CONCLUSIONS: The outbreak of Ebola Virus Disease in West
      Africa resulted in significant strengthening of Ireland's Port Health
      preparedness, while also highlighting the extent to which preparedness requires
      ongoing and sustained commitment from all stakeholders, both nationally and
      internationally, in ensuring that countries are ready when the next threat
      presents at their borders.

PMID- 27871326
TI  - Tryptophan hydroxylase 1 and 5-HT7 receptor preferentially expressed in triple
      negative breast cancer promote cancer progression through autocrine serotonin
      signaling.
AB  - BACKGROUND: Triple-negative breast cancer (TNBC) has a high risk of relapse and
      there are few chemotherapy options. Although 5-hydroxytryptamine (5-HT,
      serotonin) signaling pathways have been suggested as potential targets for anti
      cancer drug development, the mechanism responsible for the action of 5-HT in TNBC
      remains unknown. METHODS: Quantitative real-time polymerase chain reaction (qRT
      PCR) and Western blotting were used to measure mRNA and protein levels,
      respectively. Cell proliferation was measured using CellTiter 96 Aqueous One
      Solution. siRNA transfection was used to assess involvement of genes in cancer
      invasion, which were identified by Matrigel transwell invasion assay. Levels of 5
      HT and vascular endothelial growth factor (VEGF) were measured using ELISA kits.
      Chick chorioallantoic membrane (CAM) assay and mouse tumor model were used to
      investigate the in vivo effects of SB269970, a 5-HT7 receptor antagonist, and BJ
      1113, a novel synthetic compound. RESULTS: TNBC cell lines (MDA-MB-231, HCC-1395,
      and Hs578T) expressed higher levels of tryptophan hydroxylase 1 (TPH1) than
      hormone-responsive breast cancer cell lines (MCF-7 and T47D). In MDA-MB-231
      cells, 5-HT promoted invasion and proliferation via 5-HT7 receptor, and
      interestingly, the stimulatory effect of 5-HT on MDA-MB-231 cell invasion was
      stronger than its effect on proliferation. Likewise, downstream signaling
      pathways of 5-HT7 differed during invasion and proliferation, that is, Galpha
      activated cAMP and Gbetagamma-activated kinase signaling during invasion, and
      Gbetagamma-activated PI3K/Akt signaling during proliferation. Also, 5-HT
      increased the protein expressions of TPH1 and VEGF in MDA-MB-231 cells. These
      results provide insight of the stimulatory effect of 5-HT on breast cancer
      progression; 5-HT was found to act more strongly during the first stage of
      metastasis (during invasion and migration) than during the later proliferative
      phase after local invasion. Interestingly, these actions of 5-HT were inhibited
      by BJ-1113, a 6-amino-2,4,5-trimethylpyridin-3-ol analog. BJ-1113 blocked
      intracellular signaling pathways initiated by 5-HT7 receptor activation, and
      exhibited anti-proliferative and anti-invasive activities against MDA-MB-231
      cells. Furthermore, the inhibitory effect of BJ-1113 against MDA-MB-231 tumor
      growth was greater than that of SB269970, a 5-HT7 receptor antagonist.
      CONCLUSIONS: 5-HT7 receptor which mediates 5-HT-induced cancer progression is a
      potential therapeutic target in TNBC, and BJ-1113 offers a novel scaffold for the
      development of anti-cancer agents against TNBC.

PMID- 27871328
TI  - Membrane bound modified form of clade B Env, JRCSF is suitable for immunogen
      design as it is efficiently cleaved and displays all the broadly neutralizing
      epitopes including V2 and C2 domain-dependent conformational epitopes.
AB  - BACKGROUND: Antigenicity of HIV-1 envelope proteins (Envs) of both lab-adapted
      and primary isolates expressed on the cell surface rarely match with in vitro
      neutralization of viruses, pseudo-typed with corresponding Envs. Often, both
      neutralizing and non-neutralizing antibodies bind to Envs expressed on the cell
      membrane. This could be due to the lack of efficient cleavage of Env expressed on
      the cell surface. Naturally occurring, efficiently cleaved Envs with appropriate
      antigenic properties are relatively rare. Given viral diversity it is essential
      to increase the pool of candidate Envs suitable for immunogen design. Previously,
      it has been reported that JRFL Env is the only clade B Env, which is efficiently
      cleaved on the cell surface and retains desirable antigenic properties. JRCSF is
      a clade B Env isolated from the same patient as JRFL. JRCSF Env has not been
      explored aggressively for designing immunogen as the binding characteristics of
      JRCSF Env to broadly neutralizing antibodies on the cell surface and its cleavage
      status are unknown. RESULTS: Although JRCSF preferentially binds to most of the
      other gp120-directed neutralizing antibodies and cleavage dependent antibody,
      PGT151 efficiently, it binds poorly to CD4-binding-site-directed (CD4-bs
      directed) neutralizing antibodies on cell surface. Membrane bound form of
      modified JRCSF Env containing the N197D mutation binds to CD4-bs-directed
      neutralizing antibodies better than JRFL, without debilitating its ability to
      bind quaternary epitope-directed neutralizing antibodies or exposing the CD4i
      antibody epitopes. In comparison to JRFL (E168K), JRCSF Env binds more
      efficiently to PG9/PGT145 class of V1/V2-directed conformational antibodies.
      Biochemical, cell surface staining and gp120 shedding experiments suggest that
      JRCSF is efficiently cleaved on the cell surface. CONCLUSIONS: Binding of JRCSF
      Env expressed on cell surface to the various HIV-1 Env-directed antibodies has
      not been reported earlier. Here, for the first time, we report that compared to
      JRFL, JRCSF displays epitopes for a larger number of broadly neutralizing
      antibodies and is also efficiently cleaved when expressed on the cell surface.
      Thus, considering the diversity of viral Envs and the discovery of conformation
      dependent glycan-directed antibodies in HIV-1 infected individuals, an innately
      cleaved JRCSF Env as present on the viral membrane and displaying those distinct
      epitopes may be an important candidate for immunogen design.

PMID- 27871329
TI  - High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal
      program, correlates with poor prognosis of squamous cell carcinoma of the tongue.
AB  - BACKGROUND: Squamous cell carcinoma of the tongue (tongue SCC) is a major subtype
      of head and neck squamous cell carcinoma (HNSCC), which is an intractable cancer
      under current therapeutics. ARF6 and its effector AMAP1 are often overexpressed
      in different types of cancers, such as breast cancer and renal cancer, and in
      these cancers, AMAP1 binds to EPB41L5 to promote invasion, metastasis, and drug
      resistance. EPB41L5 is a mesenchymal-specific protein, normally induced during
      epithelial-mesenchymal transition (EMT) to promote focal adhesion dynamics.
      Similarly to breast cancer and renal cancer, the acquisition of mesenchymal
      phenotypes is the key process that drives the malignancy of HNSCC. We previously
      showed that the overexpression of AMAP1 in tongue SCC is statistically correlated
      with the poor outcome of patients. In this study, we examined whether tongue SCC
      also expresses EPB41L5 at high levels. RESULTS: Immunohistochemical staining of
      clinical specimens of tongue SCC demonstrated that high expression levels of
      EPB41L5 statistically correlate with poor disease-free survival and poor overall
      survival rates of patients. The tongue SCC cell line SCC-9, which overexpress
      Arf6 and AMAP1, also expressed EPB41L5 at high levels to promote invasiveness,
      whereas the weakly invasive SCC-25 cells did not express EPB41L5 at notable
      levels. Among the different EMT-associated transcriptional factors, ZEB1 was
      previously found to be most crucial in inducing EPB41L5 in breast cancer and
      renal cancer. In contrast, expression levels of ZEB1 did not correlate with the
      expression levels of EPB41L5 in tongue SCC, whereas KLF8 and FOXO3 levels showed
      positive correlations with EPB41L5 levels. Moreover, silencing of EPB41L5 only
      marginally improved the drug resistance of SCC-9 cells, even when coupled with
      ionizing radiation. CONCLUSION: Our results indicate that activation of the
      cancer mesenchymal program in tongue SCC, which leads to EPB41L5 expression,
      closely correlates with the poor prognosis of patients. However, ZEB1 was not the
      major inducer of EPB41L5 in tongue SCC, unlike in breast cancer and renal cancer.
      Thus, processes that trigger the mesenchymal program of tongue SCC, which drives
      their malignancies, seem to be substantially different from those of other
      cancers.

PMID- 27871330
TI  - Age is not a determinant factor in susceptibility of broilers to H5N2 clade
      2.3.4.4 high pathogenicity avian influenza virus.
AB  - In 2014-2015, the US experienced an unprecedented outbreak of H5 clade 2.3.4.4
      highly pathogenic avian influenza (HPAI) virus. The H5N2 HPAI virus outbreak in
      the Midwest in 2015 affected commercial turkey and layer farms, but not broiler
      farms. To assess any potential genetic resistance of broilers and/or age-related
      effects, we investigated the pathogenesis and transmission of
      A/turkey/Minnesota/12582/2015 (H5N2) (Tk/MN/15) virus in commercial 5-week-old
      broilers, 8-week-old broilers, and >30-week-old broiler breeders. The mean bird
      lethal dose (BLD50) was 5.0 log10 mean egg infectious dose (EID50) for all age
      groups. The mean death time (MDT) was statistically not different among the three
      age groups, ranging between 3.2 and 4.8 days. All broilers that became infected
      shed high levels of virus with transmission to contacts and demonstrated severe
      pathology. Mortality and virus shedding results indicated that age is not a
      determinant factor in susceptibility of broilers to H5N2 clade 2.3.4.4 HPAI
      virus. Previously, the Tk/MN/15 virus had a BLD50 of 3.6 log10 EID50 and MDT of 2
      days in White Leghorn chickens and a BLD50 of 5.0 log10 EID50 and MDT of 5.9 days
      in turkeys, suggesting that the broiler breed is less susceptible to Midwestern
      H5N2 virus than the layer breed but similarly susceptible to turkeys. Therefore,
      genetic resistance of broilers to infection may have accounted only partially for
      the lack of affected broiler farms in the Midwestern outbreaks, with other
      contributing factors such as fewer outside to on farm exposure to contacts, type
      of production management system or enhanced biosecurity.

PMID- 27871331
TI  - Association of DARS gene polymorphisms with the risk of isolated ventricular
      septal defects in the Chinese Han population.
AB  - BACKGROUND: Ventricular septal defects (VSD) are the most common subtype of
      congenital heart defects (CHD) and are estimated to account for 20 to 30% of all
      cases of CHD. The etiology of isolated VSD remains poorly understood. Eight core
      aminoacyl-tRNA synthetases (ARSs) (EPRS, MARS, QARS, RARS, IARS, LARS, KARS, and
      DARS) combine with three nonenzymatic components to form a complex known as the
      multisynthetase complex (MSC). Four single nucleotide polymorphisms (SNPs) in
      EPRS have been reported to be associated with risks of CHD in Chinese
      populations. METHODS: In this study, we hypothesize that SNPs of the DARS gene
      might influence susceptibility to sporadic isolated VSD. Therefore, we conducted
      a case-control study of 841 patients with isolated VSD and 2953 non-CHD controls
      from the Chinese Han population to evaluate how 4 potentially functional SNPs
      within the DARS gene were associated with the risk of VSD. RESULTS: We observed
      that the risk of VSD was significantly associated with rs2164331 [G/A; odds ratio
      (OR) = 0.78, 95% confidence interval (CI) = 0.69-0.91; P = 3.17 * 10-3],
      rs6738266 [G/A; OR = 1.17, 95% CI = 1.05-1.29, P = 1.83 * 10-3], and rs309143
      [G/A; OR = 1.09, 95% CI = 1.01-1.17; P = 3.12 * 10-2]. Additionally, compared
      with individuals with 0-2 risk alleles, individuals carrying 3, 4, and 5 or more
      risk alleles had 1.01-, 1.22- and 1.46-fold greater risks of VSD, respectively.
      These findings revealed a significant dose-response effect for VSD risk among
      individuals carrying different numbers of risk alleles (Ptrend = 6.37 * 10-4).
      CONCLUSIONS: These findings indicate that genetic variants of the DARS gene may
      influence individual susceptibility to isolated VSD in the Chinese Han
      population.

PMID- 27871332
TI  - The prevalence of novel psychoactive substances (NPS) use in non-clinical
      populations: a systematic review protocol.
AB  - BACKGROUND: Novel psychoactive substances (NPS) are new narcotic or psychotropic
      drugs that are not controlled by the United Nations drug convention that may pose
      a serious public health threat due to their wide availability for purchase on the
      internet and in so called "head shops." Yet, the extent of their global use
      remains largely unknown. The aim of this study is to conduct a systematic review
      of the prevalence of NPS use in non-clinical populations. METHODS: This is a
      systematic review of observational studies. Embase, MEDLINE, PubMed, Cumulative
      Index to Nursing and Allied Health (CINAHL), Cochrane Library, Lilacs, Scopus,
      Global Health, PsychINFO, Web of Science, and the World Health Organization (WHO)
      regional databases will be searched for eligible prevalence studies published
      between 2010 and 2016. Data from cross-sectional studies that report the
      prevalence of NPS use (one or more types) in participants (of any age) from
      censuses or probabilistic or convenience samples will be included. Data will be
      extracted from eligible publications, using a data extraction tool developed for
      this study. Visual and statistical approaches will be adopted instead of
      traditional meta-analytic approaches. DISCUSSION: This review will describe the
      distributions of various types of prevalence estimates of NPS use and explore the
      impact of different population groups and study-related and tempo-geographical
      variables on characteristics of these distributions over the period of 2010 to
      2016. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037020.

PMID- 27871333
TI  - Building a competent health manager at district level: a grounded theory study
      from Eastern Uganda.
AB  - BACKGROUND: Health systems in low-income countries are often characterized by
      poor health outcomes. While many reasons have been advanced to explain the
      persistently poor outcomes, management of the system has been found to play a key
      role. According to a WHO framework, the management of health systems is central
      to its ability to deliver needed health services. In this study, we examined how
      district managers in a rural setting in Uganda perceived existing approaches to
      strengthening management so as to provide a pragmatic and synergistic model for
      improving management capacity building. METHODS: Twenty-two interviews were
      conducted with district level administrative and political managers, district
      level health managers and health facility managers to understand their
      perceptions and definitions of management and capacity building. Kathy Charmaz's
      constructive approach to grounded theory informed the data analysis process.
      RESULTS: An interative, dynamic and complex model with three sub-process of
      building a competent health manager was developed. A competent manager was
      understood as one who knew his/her roles, was well informed and was empowered to
      execute management functions. Professionalizing health managers which was viewed
      as the foundation, the use of engaging learning approaches as the inside contents
      and having a supportive work environment the frame of the model were the sub
      processes involved in the model. The sub-processes were interconnected although
      the respondents agreed that having a supportive work environment was more time
      and effort intensive relative to the other two sub-processes. CONCLUSIONS: The
      model developed in our study makes four central contributions to enhance the WHO
      framework and the existing literature. First, it emphasizes management capacity
      building as an iterative, dynamic and complex process rather than a set of
      characteristics of competent managers. Second, our model suggests the need for
      professionalization of health managers at different levels of the health system.
      Third, our model underscores the benefits that could be accrued from the use of
      engaging learning approaches through prolonged and sustained processes that act
      in synergy. Lastly, our model postulates that different resource investments and
      a varied range of stakeholders could be required at each of the sub-processes.

PMID- 27871335
TI  - Aldehyde dehydrogenase expression in Metaphire posthuma as a bioindicator to
      monitor heavy metal pollution in soil.
AB  - BACKGROUND: Soil contamination and associated pollution plays a detrimental role
      in soil flora and fauna. Soil is processed and remodeled by subterranean
      earthworms, accordingly are referred to as soil chemical engineers. These worms,
      besides processing carbon and nitrogen, serve as minors for processing metals. In
      heavy metal contaminated soils, they accumulate heavy metals, which in turn cause
      altered gene expression, including aldehyde dehydrogenase (ALDH) enzymes. This
      study explores the possibility of ALDH expression in earthworms as a novel
      biomarker for the heavy metal contamination of soil. RESULTS: Earthworms cultured
      in contaminated soils accumulated significantly higher levels of Pb and Cd.
      Similarly, significantly higher levels of ALDH enzyme activities were observed in
      earthworms cultured in soils contaminated with Pb and Cd. The ALDH activity was
      found to be highest in worms cultured in 5 ppm heavy metal contaminated soils.
      Although, ALDH activities decreased as the heavy metal concentration in soil
      increased, they were significantly higher when compared to control worms cultured
      in uncontaminated soils. The accumulation of heavy metal in earthworms measured
      after 28 days decreased as the heavy metal concentration in soil increased.
      CONCLUSIONS: Levels of ALDH expression correlated with total Pb and Cd
      concentration in the earthworm tissue. This study showed that the ALDH activity
      in earthworms could potentially be used as a biomarker to show heavy metal
      pollution in soil.

PMID- 27871337
TI  - The great spruce bark beetle (Dendroctonus micans Kug.) (Coleoptera: Scolytidae)
      in Lithuania: occurrence, phenology, morphology and communities of associated
      fungi.
AB  - We studied the occurrence, morphology and phenology of Dendroctonus micans in
      Lithuania and the fungi associated with the beetle at different developmental
      stages. The occurrence of D. micans was assessed in 19 seed orchards (at least 40
      years old) of Picea abies (L. Karst.) situated in different parts of the country.
      Bark beetle phenology was studied in two sites: a seed orchard of P. abies and a
      plantation of Picea pungens (Engelm.). D. micans morphology was assessed under
      the dissection microscope using individuals at different developmental stages
      that were sampled during phenology observations. Communities of fungi associated
      with D. micans were studied using both fungal culturing methods and direct high
      throughput sequencing from D. micans. Results showed that the incidence D. micans
      was relatively rare and D. micans was mainly detected in central and eastern
      Lithuania. The life cycle included the following stages: adult, egg, I-V
      developmental stage larvae and pupa. However, development of D. micans was
      quicker and its nests larger under the bark of P. pungens than of P. abies,
      indicating the effect of the host species. Fungal culturing and direct high
      throughput sequencing revealed that D. micans associated fungi communities were
      species rich and dominated by yeasts from a class Saccharomycetes. In total, 319
      fungal taxa were sequenced, among which Peterozyma toletana (37.5% of all fungal
      sequences), Yamadazyma scolyti (30.0%) and Kuraishia capsulate (17.7%) were the
      most common. Plant pathogens and blue stain fungi were also detected suggesting
      their potentially negative effects to both tree health and timber quality.

PMID- 27871338
TI  - Mathematical subtleties and scientific knowledge: Francis Bacon and mathematics,
      at the crossing of two traditions.
AB  - This article engages the much-debated role of mathematics in Bacon's philosophy
      and inductive method at large. The many references to mathematics in Bacon's
      works are considered in the context of the humanist reform of the curriculum
      studiorum and, in particular, through a comparison with the kinds of natural and
      intellectual subtlety as they are defined by many sixteenth-century authors,
      including Cardano, Scaliger and Montaigne. Additionally, this article gives a
      nuanced background to the 'subtlety' commonly thought to have been eschewed by
      Bacon and by Bacon's self-proclaimed followers in the Royal Society of London.
      The aim of this article is ultimately to demonstrate that Bacon did not reject
      the use of mathematics in natural philosophy altogether. Instead, he hoped that
      following the Great Instauration a kind of non-abstract mathematics could be
      founded: a kind of mathematics which was to serve natural philosophy by enabling
      men to grasp the intrinsic subtlety of nature. Rather than mathematizing nature,
      it was mathematics that needed to be 'naturalized'.

PMID- 27871336
TI  - ZFAS1: a long noncoding RNA associated with ribosomes in breast cancer cells.
AB  - BACKGROUND: Most of the eukaryotic genome is transcribed, yielding a complex
      network of transcripts including thousands of lncRNAs that generally lack protein
      coding potential. However, only a small percentage of these molecules has been
      functionally characterised, and discoveries of specific functions demonstrate
      layers of complexity. A large percentage of lncRNAs is located in the cytoplasm,
      associated with ribosomes but the function of the majority of these transcripts
      is unclear. The current study analyses putative mechanisms of action of the
      lncRNA species member ZFAS1 that was initially discovered by microarray analysis
      of murine tissues undergoing mammary gland development. As developmental genes
      are often deregulated in cancer, here we have studied its function in breast
      cancer cell lines. RESULTS: Using human breast cancer cell lines, ZFAS1 was found
      to be expressed in all cell lines tested, albeit at different levels of
      abundance. Following subcellular fractionation, human ZFAS1 was found in both
      nucleus and cytoplasm (as is the mouse orthologue) in an isoform-independent
      manner. Sucrose gradients based on velocity sedimentation were utilised to
      separate the different components of total cell lysate, and surprisingly ZFAS1
      was primarily co-localised with light polysomes. Further investigation into
      ribosome association through subunit dissociation studies showed that ZFAS1 was
      predominantly associated with the 40S small ribosomal subunit. The expression
      levels of ZFAS1 and of mRNAs encoding several ribosomal proteins that have roles
      in ribosome assembly, production and maturation were tightly correlated. ZFAS1
      knockdown significantly reduced RPS6 phosphorylation. CONCLUSION: A large number
      of lncRNAs associate with ribosomes but the function of the majority of these
      lncRNAs has not been elucidated. The association of the lncRNA ZFAS1 with a
      subpopulation of ribosomes and the correlation with expression of mRNAs for
      ribosomal proteins suggest a ribosome-interacting mechanism pertaining to their
      assembly or biosynthetic activity. ZFAS1 may represent a new class of lncRNAs
      which associates with ribosomes to regulate their function. REVIEWERS: This
      article was reviewed by Christine Vande Velde, Nicola Aceto and Haruhiko Siomi.

PMID- 27871334
TI  - Exploiting members of the BAHD acyltransferase family to synthesize multiple
      hydroxycinnamate and benzoate conjugates in yeast.
AB  - BACKGROUND: BAHD acyltransferases, named after the first four biochemically
      characterized enzymes of the group, are plant-specific enzymes that catalyze the
      transfer of coenzyme A-activated donors onto various acceptor molecules. They are
      responsible for the synthesis in plants of a myriad of secondary metabolites,
      some of which are beneficial for humans either as therapeutics or as specialty
      chemicals such as flavors and fragrances. The production of pharmaceutical,
      nutraceutical and commodity chemicals using engineered microbes is an
      alternative, green route to energy-intensive chemical syntheses that consume
      petroleum-based precursors. However, identification of appropriate enzymes and
      validation of their functional expression in heterologous hosts is a prerequisite
      for the design and implementation of metabolic pathways in microbes for the
      synthesis of such target chemicals. RESULTS: For the synthesis of valuable
      metabolites in the yeast Saccharomyces cerevisiae, we selected BAHD
      acyltransferases based on their preferred donor and acceptor substrates. In
      particular, BAHDs that use hydroxycinnamoyl-CoAs and/or benzoyl-CoA as donors
      were targeted because a large number of molecules beneficial to humans belong to
      this family of hydroxycinnamate and benzoate conjugates. The selected BAHD coding
      sequences were synthesized and cloned individually on a vector containing the
      Arabidopsis gene At4CL5, which encodes a promiscuous 4-coumarate:CoA ligase
      active on hydroxycinnamates and benzoates. The various S. cerevisiae strains
      obtained for co-expression of At4CL5 with the different BAHDs effectively
      produced a wide array of valuable hydroxycinnamate and benzoate conjugates upon
      addition of adequate combinations of donors and acceptor molecules. In
      particular, we report here for the first time the production in yeast of
      rosmarinic acid and its derivatives, quinate hydroxycinnamate esters such as
      chlorogenic acid, and glycerol hydroxycinnamate esters. Similarly, we achieved
      for the first time the microbial production of polyamine hydroxycinnamate amides;
      monolignol, malate and fatty alcohol hydroxycinnamate esters; tropane alkaloids;
      and benzoate/caffeate alcohol esters. In some instances, the additional
      expression of Flavobacterium johnsoniae tyrosine ammonia-lyase (FjTAL) allowed
      the synthesis of p-coumarate conjugates and eliminated the need to supplement the
      culture media with 4-hydroxycinnamate. CONCLUSION: We demonstrate in this study
      the effectiveness of expressing members of the plant BAHD acyltransferase family
      in yeast for the synthesis of numerous valuable hydroxycinnamate and benzoate
      conjugates.

PMID- 27871339
TI  - Methodological considerations for research on ethnopolitical violence.
AB  - The methodological and epistemological challenges that research on ethnopolitical
      violence faces are examined. This research area is fundamentally important for
      political reasons and for understanding, as well as subsequent interventions to
      ameliorate, youths' responses to ethnopolitical violence. Advances in methods are
      reviewed that can overcome the obstacles placed by the various challenges. These
      issues are discussed in the context of the articles that comprise this Special
      Section.

PMID- 27871340
TI  - Afit: a bioinformatic tool for measuring aphid fitness and invasiveness.
AB  - A careful measure of fitness represents a crucial target in crop pest management
      and becomes fundamental considering extremely prolific insects. In the present
      paper, we describe a standardized rearing protocol and a bioinformatics tool to
      calculate aphid fitness indices and invasiveness starting from life table data.
      We tested the protocol and the bioinformatic tool using six Myzus persicae
      (Sulzer) asexual lineages in order to investigate if karyotype rearrangements and
      ecotype could influence their reproductive performances. The tool showed that
      different karyotypes do not influence adaptive success and put in evidence a
      marked invasive potential of the M. persicae lineage 64. The presence of a
      similar fitness rate of 33H and 7GK asexual lineages (both possessing intra
      individual karyotype variations) in respect to the asexual lineage 1 (with a
      standard karyotype) represents an important demonstration of the potentiality of
      holocentric chromosomes to reduce the effects of chromosome rearrangements.

PMID- 27871341
TI  - Functional analysis of a NF-kappaB transcription factor in the immune defense of
      Oriental fruit fly, Bactrocera dorsalis Hendel (Diptera: Tephritidae).
AB  - Although some novel antimicrobial peptides (AMP) have been successfully isolated
      from Bactrocera dorsalis Hendel, the mechanisms underlying the induction of these
      peptides are still elusive. The homolog of NF-kappaB transcription factor Relish,
      designated as BdRelish, was cloned from B. dorsalis. The full length cDNA of
      BdRelish is 3954 bp with an open reading frame that encodes 1013 amino acids.
      Similar to Drosophila Relish and the mammalian p100, it is a compound protein
      containing a conserved Rel homology domain, an IPT (Ig-like, plexins,
      transcription factors) domain and an IkappaB-like domain (four ankyrin repeats),
      the nuclear localization signal RKRRR is also detected at the residues 449-453,
      suggesting that it has homology to Relish and it is a member of the Rel family of
      transcription activator proteins. Reverse transcription quantitative polymerase
      chain reaction analysis reveals that BdRelish mRNAs are detected in different
      quantities from various tissues and the highest transcription level of BdRelish
      is determined in fat body. The injection challenge of Escherichia coli and
      Staphylococcus aureas significantly upregulated the expression of BdRelish. The
      injection of BdRelish dsRNA markedly reduced the expression of BdRelish and
      decreased the transcription magnitude of antimicrobial peptides. Individuals
      injected BdRelish dsRNA died at a significantly faster rate compared with the
      control groups. Therefore, BdRelish is vital for the transcription of AMPs to
      attack the invading bacteria.

PMID- 27871342
TI  - Campbell de Morgan Spot, Better Known As a Cherry Angioma.

PMID- 27871343
TI  - Proximal Nail Fold Hematoma Due to Pulse Oximeter.

PMID- 27871344
TI  - Hair and Aging.
AB  - Hair is the ultimate personal beauty tool of self-expression. It is more
      malleable than skin and it is more personal than clothing; however, hair does not
      remain constant with age. Hair is arguably in peak condition at about 30 years of
      age. With time, there is a gradual change in many aspects of hair: hair diameter
      is reduced, hair density is decreased, androgenic alopecia may develop, and
      pigmentation may be diminished, producing a significant psychological impact.
      These age-related changes can be exacerbated by blast drying, heat straightening,
      perming, and coloring. In this review, the changes in hair fiber and array
      (collection of fiber) properties that occur during aging and the impact on
      styling and potential interventions that consumers undergo to circumvent these
      issues are discussed.

PMID- 27871345
TI  - Terra Firma-Forme Dermatosis in Singaporean Patients: The "Alcohol Wipe" Sign.
AB  - The term terra firma-forme dermatosis arises from the Latin phrase terra firma,
      meaning dry land (dirt), thus implying dirt-like dermatosis. The authors
      highlight five cases of patients with terra firma-forme dermatosis presenting to
      our dermatology center between 2012 and 2013. All patients presented to the
      dermatologist for persistent reticulated brown patches on the skin. These
      patients ranged in age from 6 to 22 years. All patients had tried various
      cleansing soaps and agents but were unable to remove the patches. The condition
      was cosmetically unacceptable to the patients and parents. Clinically, these
      patients had reticulated brown patches. Rubbing 70% isopropyl alcohol wipes on
      the affected areas demonstrated clearance of the brown pigmented patches in all
      cases. The diagnosis of terra firma-forme dermatosis (TFFD) was confirmed by
      forceful rubbing with a gauze pad immersed in 70% isopropyl alcohol or ethyl
      alcohol. Patients should be reassured about the benign nature of TFFD and
      educated about the cleaning procedure. Recognition of this condition can assist
      physicians in making a diagnosis and therapy with a simple alcohol wipe,
      preventing further unnecessary tests for patients.

PMID- 27871346
TI  - Woronoff Ring: A Novel Manifestation of Molluscum Contagiosum.
AB  - Woronoff ring has been mostly discussed as a phenomenon in psoriasis, especially
      during therapy. It has also been reported in a few other conditions unrelated to
      psoriasis; however, the association of Woronoff ring has not been reported in
      immunocompetent, healthy, and untreated patients with molluscum contagiosum who
      have no apparent systemic illness. The authors report a case series of Woronoff
      ring seen in untreated immunocompetent patients with molluscum contagiosum
      involving different age groups.

PMID- 27871347
TI  - Dermatomyositis-Part 2: Diagnosis, Association With Malignancy, and Treatment.
AB  - In this second part of the series on dermatomyositis, the diagnosis and its
      criteria with review of autoantibodies, capillaroscopy, imaging exams,
      histopathology, muscle biopsy, electroneuromyography, and muscular enzymes will
      be assessed. The association with malignancy, since it is described as
      paraneoplasic, will be discussed. The different therapeutic options for this
      disease will also be reported, including for dystrophic calcification, a rare and
      late complication of dermatomyositis.

PMID- 27871349
TI  - Alopecia Areata-Part III: Prognosis and Treatment.
AB  - The prognosis of alopecia areata is better in cases with single and small
      lesions, and the variability of the extension of the disease is one of the
      criteria for the choice of treatment modality. Several medications have been
      described in the literature for the treatment of alopecia areata, including
      corticosteroids, minoxidil, and diphencyprone. The authors review treatments for
      alopecia areata.

PMID- 27871350
TI  - Early Description of Diet-Induced Blistering Skin Diseases in Medieval Persia:
      Avicenna's Point of View.
AB  - Pemphigus is an autoimmune blistering skin disease that is strongly associated
      with different environmental factors. Among these, nutritional factors are
      considered to trigger pemphigus; however, their role may be underestimated.
      Investigated more recently in conventional medicine, this causative bond between
      dietary factors and blistering skin diseases was mentioned by Persian scholars
      such as Avicenna a thousand years ago. Avicenna, a well-known Persian physician
      and philosopher, who could be considered a pioneer in dermatology, discussed skin
      diseases in a chapter in The Canon of Medicine. He accounted for some nutritional
      triggers for skin blisters (mentioned as "hot swellings"), such as onion, garlic,
      leek, pepper, and wine. His precise description of causative factors based on
      principles of traditional Persian medicine (TPM) is appreciable and might well
      lead us to find more efficient ways for the prevention and treatment of
      blistering skin diseases.

PMID- 27871351
TI  - The Skin: A Time Capsule.

PMID- 27871352
TI  - What Is New in the Management of Alopecia Areata.

PMID- 27871354
TI  - Trench Foot.

PMID- 27871353
TI  - Becoming Wiser About the Wiesner Nevus.

PMID- 27871355
TI  - Desquamative Dermatitis Caused by Erlotinib: An Underreported Cutaneous Adverse
      Event.

PMID- 27871356
TI  - A Pigmented Subcutaneous Nodule on the Scalp.
AB  - A 52-year-old man presented to his primary doctor with a slow-growing cystic
      lesion on his occipital scalp. His primary care doctor diagnosed the lesion as a
      pilar cyst and recommended observation because the lesion was asymptomatic at
      that time. The patient had no significant medical or surgical history. There was
      no family history of skin cancer or other malignancies.

PMID- 27871357
TI  - Contact Urticaria With Paraphenylene Diamine, Rare or Underreported?
AB  - A 45-year old woman presented with a 2-day history of intensely itchy,
      erythematous wheals over her scalp and around her eyes, ears, and front of the
      chest. She had applied hair color and immediately developed hives on the scalp,
      face, and chest with rhinitis and redness in the eyes. The lesions recovered
      within a half hour of taking a cetirizine 10-mg tablet. She gave a similar
      history around three times in the past 6 months. She used a different brand of
      hair color every time but all were associated with the same symptoms. In the
      first and second episodes, the itchy wheals were localized to the scalp, but in
      the present episode it was most severe with eye and nasal mucosal involvement and
      lesions spreading to involve the face, ears, and chest. There was no oozing or
      eczematization present. All episodes responded well to oral cetrizine.

PMID- 27871358
TI  - Unna Nevus: Early Presentation in a 10-Year-Old Girl.
AB  - A 10-year-old girl presented with three asymptomatic raised lesions over the
      dorsal aspect of her left index finger present for the past 7 years. On
      examination, there were three skin-colored nodules overlying the middle and
      distal phalanx of her left index finger, without any attachment to the underlying
      structures (Figure 1) The nodule over the distal phalanx was the largest with a
      cobblestone-like surface. All the nodules were firm to touch. Cutaneous, mucosa,
      hair, nails, and systemic examinations were within normal limits. The two smaller
      nodules were excised under local anesthesia and sent for histopathologic
      examination. Histologic study from one of the representative lesion showed type B
      nevus cells (lymphocytoid), located in the expanded papillary dermis (Figures 2
      and 3).

PMID- 27871360
TI  - Consequences.

PMID- 27871359
TI  - Focal Epithelial Hyperplasia in Adult Patients With HIV Infection: Clearance With
      Topical Imiquimod.
AB  - Case 1 A 41-year-old man with human immunodeficiency virus (HIV) 1 diagnosed 16
      years prior to his consultation was referred for an 8-month history of multiple
      painless lumps in his mouth. He had A2 status (CD4 cell count of 273 cells/mm3
      and viral load of 43,000 copies/L) and was taking treatment with
      lamivudine/zidovudine (combivir) and efavirenz. Physical examination showed
      multiple small mucosal-colored and lobulated papulonodules located in the palate
      and lower gingiva and a whitish verrucous plaque on the lower labial mucosa
      (Figure 1a). The lesions were diagnosed clinically as focal epithelial
      hyperplasia (FEH) and further confirmed by classical histopathological findings
      (Figure 1b). He had previously received unspecified treatment; thus, topical 5%
      imiquimod cream was initiated every night. Mild erosion and ulceration developed
      in the upper labial mucosa, which were managed with lubrication (petrolatum
      ointment). After 2 weeks, all of the small lesions disappeared and the largest
      plaque resolved 1 week later (Figure 1c). A small residual mass in the area of
      biopsy, suggesting a scar, remained on the lower lip. The area was removed
      surgically and corresponded to fibrosis histologically, with no evidence of human
      papillomavirus (HPV) infection. CD4 cell count (694 cells/mm3) and viral load
      (<40 copies/L) did not show remarkable changes after imiquimod administration. No
      serious side effects were observed and the patient has remained free of disease
      after 1 year of follow-up.

PMID- 27871363
TI  - Special Issue: Respiratory Neuroplasticity.

PMID- 27871361
TI  - Recreating the synthesis of starch granules in yeast.
AB  - Starch, as the major nutritional component of our staple crops and a feedstock
      for industry, is a vital plant product. It is composed of glucose polymers that
      form massive semi-crystalline granules. Its precise structure and composition
      determine its functionality and thus applications; however, there is no versatile
      model system allowing the relationships between the biosynthetic apparatus,
      glucan structure and properties to be explored. Here, we expressed the core
      Arabidopsis starch-biosynthesis pathway in Saccharomyces cerevisiae purged of its
      endogenous glycogen-metabolic enzymes. Systematic variation of the set of
      biosynthetic enzymes illustrated how each affects glucan structure and
      solubility. Expression of the complete set resulted in dense, insoluble granules
      with a starch-like semi-crystalline organization, demonstrating that this system
      indeed simulates starch biosynthesis. Thus, the yeast system has the potential to
      accelerate starch research and help create a holistic understanding of starch
      granule biosynthesis, providing a basis for the targeted biotechnological
      improvement of crops.

PMID- 27871364
TI  - Corrigendum to "CD147 induces up-regulation of vascular endothelial growth factor
      in U937-derived foam cells through PI3K/AKT pathway" [Arch. Biochem. Biophys. 609
      (2016) 31-38].

PMID- 27871362
TI  - Actin is an evolutionarily-conserved damage-associated molecular pattern that
      signals tissue injury in Drosophila melanogaster.
AB  - Damage-associated molecular patterns (DAMPs) are molecules released by dead cells
      that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin
      is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic
      cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the
      tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated
      antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs
      and adaptive immunity. Administration of actin to Drosophila melanogaster
      triggers a response characterised by selective induction of STAT target genes in
      the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor,
      Domeless. Notably, this response requires signalling via Shark, the Drosophila
      orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent
      on Nox activity. Thus, extracellular actin detection via a Src-family kinase
      dependent cascade is an ancient means of detecting cell injury that precedes the
      evolution of adaptive immunity.

PMID- 27871366
TI  - Metalloprotease SPRTN/DVC1 Orchestrates Replication-Coupled DNA-Protein Crosslink
      Repair.
AB  - The cytotoxicity of DNA-protein crosslinks (DPCs) is largely ascribed to their
      ability to block the progression of DNA replication. DPCs frequently occur in
      cells, either as a consequence of metabolism or exogenous agents, but the
      mechanism of DPC repair is not completely understood. Here, we characterize SPRTN
      as a specialized DNA-dependent and DNA replication-coupled metalloprotease for
      DPC repair. SPRTN cleaves various DNA binding substrates during S-phase
      progression and thus protects proliferative cells from DPC toxicity. Ruijs-Aalfs
      syndrome (RJALS) patient cells with monogenic and biallelic mutations in SPRTN
      are hypersensitive to DPC-inducing agents due to a defect in DNA replication fork
      progression and the inability to eliminate DPCs. We propose that SPRTN protease
      represents a specialized DNA replication-coupled DPC repair pathway essential for
      DNA replication progression and genome stability. Defective SPRTN-dependent
      clearance of DPCs is the molecular mechanism underlying RJALS, and DPCs are
      contributing to accelerated aging and cancer.

PMID- 27871367
TI  - Conformational Control of Cascade Interference and Priming Activities in CRISPR
      Immunity.
AB  - During type I-E CRISPR-Cas immunity, the Cascade surveillance complex utilizes
      CRISPR-derived RNAs to target complementary invasive DNA for destruction. When
      invader mutation blocks this interference activity, Cascade instead triggers
      rapid primed adaptation against the invader. The molecular basis for this dual
      Cascade activity is poorly understood. Here we show that the conformation of the
      Cse1 subunit controls Cascade activity. Using FRET, we find that Cse1 exists in a
      dynamic equilibrium between "open" and "closed" conformations, and the extent to
      which the open conformation is favored directly correlates with the attenuation
      of interference and relative increase in priming activity upon target mutation.
      Additionally, the Cse1 L1 motif modulates Cascade activity by stabilizing the
      closed conformation. L1 mutations promote the open conformation and switch immune
      response from interference to priming. Our results demonstrate that Cascade
      conformation controls the functional outcome of target recognition, enabling
      tunable CRISPR immune response to combat invader evolution.

PMID- 27871365
TI  - Mechanism and Regulation of DNA-Protein Crosslink Repair by the DNA-Dependent
      Metalloprotease SPRTN.
AB  - Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with
      essential chromatin transactions, such as replication and transcription. Little
      was known about DPC-specific repair mechanisms until the recent identification of
      a DPC-processing protease in yeast. The existence of a DPC protease in higher
      eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity
      remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease
      acting in metazoans. Loss of SPRTN results in failure to repair DPCs and
      hypersensitivity to DPC-inducing agents. SPRTN accomplishes DPC processing
      through a unique DNA-induced protease activity, which is controlled by several
      sophisticated regulatory mechanisms. Cellular, biochemical, and structural
      studies define a DNA switch triggering its protease activity, a ubiquitin switch
      controlling SPRTN chromatin accessibility, and regulatory autocatalytic cleavage.
      Our data also provide a molecular explanation on how SPRTN deficiency causes the
      premature aging and cancer predisposition disorder Ruijs-Aalfs syndrome.

PMID- 27871368
TI  - Microbial bioelectrosynthesis of hydrogen: Current challenges and scale-up.
AB  - Sustainable energy supplies are needed to supplement and eventually replace
      fossil fuels. Molecular hydrogen H2 is a clean burning, high-energy fuel that is
      also used as reducing gas in industrial processes. H2 is mainly synthesized by
      steam reforming of natural gas, a non-renewable fuel. There are biosynthetic
      strategies for H2 production; however, they are associated with poor yield and
      have high cost. The application of an electrochemical driving force in a
      microbial electrolysis cell (MEC) improves the yield of biological reactions. The
      performance of the MEC is influenced by experimental parameters such as the
      electrode material, reactor design, microbial consortia and the substrate. In
      this review, factors that affect the performance of MECs are discussed and
      critically analysed. The potential for scale-up of H2 bioelectrosynthesis is also
      discussed.

PMID- 27871369
TI  - CO2 reduction and organic compounds production by photosynthetic bacteria with
      surface displayed carbonic anhydrase and inducible expression of
      phosphoenolpyruvate carboxylase.
AB  - In Rhodobacter sphaeroides, carbonic anhydrase (CA; EC 4.2.1.1) is a zinc
      containing metalloenzyme that catalyzes the reversible hydration of CO2 to HCO3-
      while phosphoenolpyruvate carboxylase (PEPC; 4.1.1.31), an enzyme involved in the
      carbon metabolism that catalyzed the fixation of CO2 to PEP, is a key factor for
      biological fixation of CO2 and enhances the production of organic compounds. In
      this study, the recombinant R. sphaeroides with highly-expressed CA was developed
      based on a surface displayed system of CA (pJY-OmpCA) on the outer membrane of R.
      sphaeroides using outer membrane protein (Omp) in R. sphaeroides, Finally, two
      more different recombinant R. sphaeroides were developed, which transformed with
      a two-vector system harboring cytosolic expressed CA (pJY-OmpCA-CA)or PEPC (pJY
      OMPCA-PEPC) in R. sphaeroides with surface displayed CA on the outer membrane. In
      case of recombinant R. sphaeroides with the pJY-OmpCA-PEPC, it has shown the
      highest CO2 reduction efficiency and the production of several organic compounds
      (carotenoids, polyhydroxybutyrate, malic acid, succinic acid). It means that the
      surface displayed CA on the R. sphaeroides would accelerate the CO2-bicabonate
      conversion on the bacterial outer membrane. Moreover, inducible over-expression
      of PEPC with surface-displayed CA was successfully used to facilitate a rapider
      CO2 reduction and quicker production of organic compounds.

PMID- 27871370
TI  - Enhanced detection of RNA by MMLV reverse transcriptase coupled with thermostable
      DNA polymerase and DNA/RNA helicase.
AB  - Detection of mRNA is a valuable method for monitoring the specific gene
      expression. In this study, we devised a novel cDNA synthesis method using three
      enzymes, the genetically engineered thermostable variant of reverse transcriptase
      (RT), MM4 (E286R/E302K/L435R/D524A) from Moloney murine leukemia virus (MMLV),
      the genetically engineered variant of family A DNA polymerase with RT activity,
      K4polL329A from thermophilic Thermotoga petrophila K4, and the DNA/RNA helicase
      Tk-EshA from a hyperthermophilic archaeon Thermococcus kodakarensis. By
      optimizing assay conditions for three enzymes using Taguchi's method, 100 to 1000
      fold higher sensitivity was achieved for cDNA synthesis than conventional assay
      condition using only RT. Our results suggest that DNA polymerase with RT activity
      and DNA/RNA helicase are useful to increase the sensitivity of cDNA synthesis.

PMID- 27871372
TI  - A Novel highly thermostable branched-chain amino acid aminotransferase from the
      crenarchaeon Vulcanisaeta moutnovskia.
AB  - A new fold-type IV branched-chain amino acid aminotransferase VMUT0738 from the
      hyperthermophilic Crenarchaeon Vulcanisaeta moutnovskia was successfully
      expressed in Escherichia coli. Purified VMUT0738 showed activity toward numerous
      aliphatic and aromatic l-amino acids and 2-oxo acids at optimal pH 8.0.
      Distinguishing features of the VMUT0738 compared with typical BCAT are the
      absence of activity toward acidic substrates, high activity toward basic ones,
      and low but detectable activity toward the (R)-enantiomer of alpha
      methylbenzylamine (0.0076U/mg) The activity of VMUT0738 increases with a rise in
      the temperature from 60 degrees C to 90 degrees C. VMUT0738 showed high
      thermostability (after 24h incubation at 70 degrees C the enzyme lost only 27% of
      the initial activity) and the resistance to organic solvents. The sequence
      alignment revealed two motifs (V/I)xLDxR and PFG(K/H)YL characteristic of BCATs
      from species of the related genera Vulcanisaeta, Pyrobaculum and Thermoproteus
      that might be responsible for the unique substrate recognition profile of the
      enzyme.

PMID- 27871371
TI  - Effect of C-terminal domain truncation of Thermus thermophilus trehalose synthase
      on its substrate specificity.
AB  - The C-terminal domain of the three-domain-comprising trehalose synthase from
      Thermus thermophilus was truncated in order to study the effect on the enzyme's
      activity and substrate specificity. Compared with the wild-type (WT) enzyme, the
      two truncated enzymes (DM1 and DM2) showed lower maltose- and trehalose
      converting activities and a different transglycosylation reaction mechanism. In
      the mutants, the glucose moiety cleaved from the maltose substrate was released
      from the enzyme and intercepted by external glucose oxidase, preventing the
      production of trehalose. The WT enzyme, however, retained the glucose in the
      active site to effectively produce trehalose. In addition, DM1 synthesized much
      higher amounts of mannose-containing disaccharide trehalose analog (Man-TA) than
      did the WT and DM2. The results suggest that the C-terminal domain in the WT
      enzyme is important for retaining the glucose moiety within the active site. The
      mutant enzymes could be used to produce Man-TA, a postulated inhibitor of gut
      disaccharidases.

PMID- 27871373
TI  - Design and production of antibodies for the detection of Streptococcus uberis.
AB  - Streptococcus uberis (S. uberis) is an important environmental pathogen causing
      mastitis in dairy cattle. Mastitis or mammary gland infection is the most common
      disease in milking cows and cause significant economic burden to farmers due to
      the reduction of the amount of milk and its quality. The development of rapid
      analytical methods for the determination of mastitis-causing pathogens in milk is
      of utmost importance for the early identification of the causes of mastitis and
      the beginning of timely treatment of cows. Combining in silico bioinformatic
      analysis and solid phase peptide synthesis using Fmoc chemistry, we have made two
      different peptides to mimic the adhesion protein of S. uberis, which is promoting
      the attachment of bacteria to epithelial cells. After purification with RP-HPLC,
      the peptides were conjugated with a larger carrier protein (KLH) and used for
      immunization of rabbits to produce specific antibodies. The separation of anti-S.
      uberis antibodies from rabbit blood antisera was carried out with affinity
      chromatography, using the synthetic peptides as affinity ligands. The purified
      antibodies showed high affinity and specificity towards S. uberis and were used
      for rapid bio-recognition and identification of S. uberis with an
      immunobiosensing system.

PMID- 27871374
TI  - Catalytic efficiency and thermostability improvement of Suc2 invertase through
      rational site-directed mutagenesis.
AB  - Engineering of invertases has come to attention because of increasing demand for
      possible applications of invertases in various industrial processes. Due to the
      known physicochemical properties, invertases from micro-organisms such as
      Saccharomyces cerevisiae carrying SUC2 gene are considered as primary models. To
      improve thermostability and catalytic efficiency of SUC2 invertase (SInv), six
      influential residues with Relative Solvent Accessibility<5% were selected through
      multiple-sequence alignments, molecular modelling, structural and computational
      analyses. Consequently, SInv and 5 mutants including three mutants with single
      point substitution [Mut1=P152V, Mut2=S85V and Mut3=K153F)], one mutant with two
      points [Mut4=S305V-N463V] and one mutant with three points [Mut5=S85V-K153F
      T271V] were developed via site-directed mutagenesis and produced using Pichia
      pastoris as the host. Physicochemical studies on these enzymes indicated that the
      selected amino acids which were located in the active site region mainly
      influenced catalytic efficiency. The best improvement belonged to Mut1 (54%
      increase in Kcat/Km) and Mut3 exhibited the worst effect (90% increase in Km).
      These results suggest that Pro152 and Lys153 play key role in preparation of the
      right substrate lodging in the active site of SInv. The best thermostability
      improvement (16%) was observed for Mut4 in which two hydrophilic residues located
      on the loops, far from the active site, were replaced by Valines. These results
      suggest that tactful simultaneous substitution of influential hydrophilic
      residues in both active site region and peripheral loops with hydrophobic amino
      acids could result in more thermostable invertases with enhanced catalytic
      efficiency.

PMID- 27871375
TI  - A novel, simple screening method for investigating the properties of lignin
      oxidative activity.
AB  - Enzymatic lignin degradation represents a key challenge for integrated
      biorefineries. Notwithstanding the rich content in aromatic compounds, lignin's
      complex structure has hampered identification of an effective and cost-efficient
      enzymatic procedure to transform it into less complex product families.
      Advancements in enzymatically modifying or degrading lignin require a simple and
      reliable analytical method to quickly screen diverse lignin samples by employing
      different enzymes and conditions. Here, we report on a novel, rapid, and economic
      colorimetric assay for lignin oxidation based on the reaction of 2,4
      dinitrophenylhydrazine with the carbonyl groups generated by enzymatic oxidation.
      The assay was validated on monomeric and dimeric lignin model compounds by
      comparison with HPLC analysis. The colorimetric method was used to investigate
      the activity of ten laccases and eight peroxidases on three technical lignins
      under different experimental conditions (e.g., by altering pH and mediator used).
      The colorimetric method was also coupled to a size-exclusion chromatographic
      separation of the lignin sample obtained after the enzymatic treatment in order
      to verify whether the enzymatic treatment resulted in lignin depolymerization,
      too. On the basis of this novel procedure, appropriate enzymatic treatments can
      now be identified to generate valuable lignin product streams.

PMID- 27871376
TI  - Optimization of oligomeric enzyme activity in ionic liquids using Rhodotorula
      glutinis yeast phenylalanine ammonia lyase.
AB  - Phenylalanine ammonia lyase (E.C.4.3.1.24, PAL) activity of Rhodotorula glutinis
      yeast has been demonstrated in four commonly used ionic liquids. PAL forward
      reaction was carried out in 1-butyl-3-methylimidazolium methyl sulfate
      ([BMIM][MeSO4]), 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]), 1
      butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) and 1-butyl-3
      methylimidazolium lactate ([BMIM][lactate]). Our experiments have revealed that
      PAL is catalytically active in ionic liquids and the enzyme activity in
      ([BMIM][PF6]) is comparable to that obtained in aqueous buffer medium. Different
      conditions were optimized for maximal PAL forward activity including time of
      incubation (30.0min)L-phenylalanine substrate concentration (30.0mM), nature of
      buffer (50.0mM Tris-HCl), pH (9.0), temperature (37 degrees C), and speed of
      agitation (100 rev min-1). Under these optimized conditions, about 83% conversion
      of substrate to product was obtained for the PAL forward reaction that was
      determined using UV spectroscopy at 290nm. PAL reverse reaction in ([BMIM][PF6])
      was determined spectrophotometrically at 520nm; and about 59% substrate
      conversion was obtained. This data provides further knowledge in enzyme
      biocatalysis in non-aqueous media, and may be of importance when studying the
      function of other oligomeric/multimeric proteins and enzymes in ionic liquids.

PMID- 27871377
TI  - Enhancement of methanol resistance of Yarrowia lipolytica lipase 2 using beta
      cyclodextrin as an additive: Insights from experiments and molecular dynamics
      simulation.
AB  - The methanol resistance of lipase is a critical parameter in enzymatic biodiesel
      production. In the present work, the methanol resistance of Yarrowia lipolytica
      Lipase 2 (YLLIP2) was significantly improved using beta-cyclodextrin (beta-CD) as
      an additive. According to the results, YLLIP2 with beta-CD exhibited
      approximately 7000U/mg specific activity in 30wt% methanol for 60min compared
      with no activity without beta-CD under the same conditions. Molecular dynamics
      (MD) simulation results indicated that the beta-CD molecules weakened the
      conformational change of YLLIP2 and maintained a semi-open state of the lid by
      overcoming the interference caused by methanol molecules. Furthermore, the beta
      CD molecule could directly stabilize "pathway" regions (e.g., Asp61-Asp67) and
      indirectly stabilize "pathway" regions (e.g., Gly44-Phe50) by forming hydrogen
      bonds with "pathway" regions and nearby "pathway" regions, respectively. The
      regions stabilized by the beta-CD molecule then prevented the closure of active
      pockets, thus retaining the enzymatic activity of YLLIP2 with beta-CD in methanol
      solvent.

PMID- 27871378
TI  - Deciphering the factors defining the pH-dependence of a commercial glycoside
      hydrolase family 8 enzyme.
AB  - A prerequisite to the use of any enzyme in any industrial process is an
      understanding of its activity and stability under process conditions. Glycoside
      hydrolase family 8 enzymes include many important biotechnological biocatalysts
      yet little is known of the performance of these with respect to pH. A better
      understanding of this parameter and its relationship to structure and function in
      these enzymes will allow for an improved use of these in industry as well as an
      enhanced ability in their engineering and optimisation for a particular
      application. An in-depth analysis of the pH induced changes in activity,
      irreversible inactivation, conformation, stability and solubility of a commercial
      glycoside hydrolase family 8 xylanase was carried out with the aim of identifying
      the factors determining the pH dependence of this enzyme. Our study showed that
      different phenomena play different roles at the various pHs examined. Both
      reversible and irreversible processes are involved at acidic pHs, with the
      irreversible processes dominating and being due to protein aggregation and
      precipitation. At basic pHs, loss of activity is principally due to reversible
      processes, possibly deprotonation of an essential catalytic residue, but at
      higher pHs, near the pI of the protein, precipitation again dominates while
      structure unfolding was discerned at the higher pHs investigated. Such insights
      demonstrate the complexity of factors involved in the pH dependence of proteins
      and advances our knowledge on design principles and concepts for engineering
      proteins. Our results highlight the major role of protein precipitation in
      activity and stability losses at both low and high pHs but it is proposed that
      different strategies be used in tailoring the enzyme to overcome this in each
      case. Indeed the detailed understanding obtained here will allow for a more
      focused, informed and hence successful tailoring of glycoside hydrolase family 8
      proteins for a specific pH and process application.

PMID- 27871379
TI  - Decolourisation of Acid orange 7 in a microbial fuel cell with a laccase-based
      biocathode: Influence of mitigating pH changes in the cathode chamber.
AB  - Biocathodes may be a suitable replacement of platinum in microbial fuel cells
      (MFCs) if the cost of MFCs is to be reduced. However, the use of enzymes as bio
      cathodes is fraught with loss of activity as time progresses. A possible cause of
      this loss in activity might be pH increase in the cathode as pH gradients in MFCs
      are well known. This pH increase is however, accompanied by simultaneous increase
      in salinity; therefore salinity may be a confounding variable. This study
      investigated various ways of mitigating pH changes in the cathode of MFCs and
      their effect on laccase activity and decolourisation of a model azo dye Acid
      orange 7 in the anode chamber. Experiments were run with catholyte pH
      automatically controlled via feedback control or by using acetate buffers (pH
      4.5) of various strength (100mM and 200mM), with CMI7000 as the cation exchange
      membrane. A comparison was also made between use of CMI7000 and Nafion 117 as the
      transport properties of cations for both membranes (hence their potential effects
      on pH changes in the cathode) are different. Results show that using Nafion 117
      membrane limits salinity and pH changes in the cathode (100mM acetate buffer as
      catholyte) leading to prolonged laccase activity and faster AO7 decolourisation
      compared to using CMI7000 as a membrane; similarly automatic pH control in the
      cathode chamber was found to be better than using 200mM acetate buffer. It is
      suggested that while pH control in the cathode chamber is important, it does not
      guarantee sustained laccase activity; as salinity increases affect the activity
      and it could be mitigated using a cation selective membrane.

PMID- 27871380
TI  - An improved amperometric L-lactate biosensor based on covalent immobilization of
      microbial lactate oxidase onto carboxylated multiwalled carbon nanotubes/copper
      nanoparticles/polyaniline modified pencil graphite electrode.
AB  - An improved amperometric l-lactate biosensor was constructed based on covalent
      immobilization of lactate oxidase (LOx) from Pediococcus species onto
      carboxylated multiwalled carbon nanotubes (cMWCNT)/copper nanoparticles
      (CuNPs)/polyaniline (PANI) hybrid film electrodeposited on the surface of a
      pencil graphite electrode (PGE). The enzyme electrode was characterized by cyclic
      voltammetry (CV), scanning electron microscopy (SEM), Fourier transform infrared
      (FTIR) spectroscopy and electrochemical impedance spectroscopy (EIS), while CuNPs
      synthesized by chemical reduction method, were characterized by transmission
      electron microscopy (TEM), UV spectrascopy and X-ray diffraction (XRD). The
      biosensor showed maximum response within 5s at pH 8.0 in 0.05M sodium phosphate
      buffer and 37 degrees C, when operated at 20mVs-1. The biosensor had a detection
      limit of 0.25MUM with a wide working range between 1MUM-2500MUM. The biosensor
      was employed for measurement of l-lactic acid level in plasma of apparently
      healthy and diseased persons. Analytical recovery of added lactic acid in plasma
      was 95.5%. Within- and between-batch coefficients of variations were 6.24% and
      4.19% respectively. There was a good correlation (R2=0.97) between plasma lactate
      values as measured by standard enzymatic spectrophotometric method and the
      present biosensor. The working enzyme electrode was used 180 times over a period
      of 140 days, when stored at 4 degrees C.

PMID- 27871381
TI  - Investigation of sulfonamides inhibition of carbonic anhydrase enzyme using
      multiphotometric and electrochemical techniques.
AB  - Two approaches for sulfonamides (SA's) determination, based on carbonic anhydrase
      enzyme inhibition have been investigated in this work. In the first method, nine
      different SA's have been screened using simultaneous multiphotometric measurement
      in multiwell plates. The sulfanilamide (SAD) showed significant inhibition
      compared to other sulfonamides. The carbonic anhydrase (CA) kinetic interactions
      reveal noncompetitive binding of SAD. Interferences from other inhibitors with
      enzyme were studied and the results showed very good selectivity toward SAD. In
      the second approach, an electrochemical enzyme inhibition biosensor, based on CA
      entrapped in a carbon paste electrode using carbon black nanoparticles and solid
      paraffin, was successfully applied to SAD measurements. Results from the
      quantitative analysis of SAD are discussed in terms of detection limit, linear
      range and sensitivity using multiphotometric and biosensor-based methods The
      biosensor developed was successfully applied to the determination of SAD at
      submicromolar levels and it is recommended for application for in situ analysis.

PMID- 27871382
TI  - Relevance of substrates and products on the desorption of lipases physically
      adsorbed on hydrophobic supports.
AB  - Lipase B from Candida antarctica (CALB) has been physically immobilized on octyl
      agarose via interfacial activation. The incubation of the enzyme in 80% ethanol
      at pH 5 and 25 degrees C has not significant effect on enzyme activity. Moreover,
      the hydrolysis of 100mM tributyrin catalyzed by this biocatalyst exhibited a
      quite linear reaction course. However, a new cycle of tributyrin hydrolysis
      showed a drastic drop in the activity. SDS-PAGE gels of the supernatant and the
      biocatalyst showed a significant enzyme desorption after the reaction. Similar
      results could be appreciated using triacetin or sunflower oil, while using 300mM
      methyl phenyl acetate, butyl butyrate or ethyl butyrate most enzyme molecules
      remained immobilized. The results show that the detergent properties of some
      reaction products increase the enzyme release from the hydrophobic support, and
      this problem increased if the concentration of the reactants increased. Using
      500mM tributyrin, even in fully aqueous medium, some enzyme desorption from the
      support may be observed. Thus, the results show a limitation of this kind of
      biocatalysts that should be considered in the selection of an industrial lipase
      biocatalyst.

PMID- 27871384
TI  - Protein-based inverse opals: A novel support for enzyme immobilization.
AB  - In this study, protein-based inverse opals were prepared for the first time by
      using the colloidal crystal templating method. The preparation process involved
      three steps including filling the templates with protein molecules, crosslinking,
      and template removal. The obtained inverse opals were used to immobilize
      Penicillin G acylase (PGA) because of its intrinsic biocompatible property. The
      immobilization process was optimized and the properties of the immobilized PGA
      (PGA@IO) were investigated. PGA@IO exhibited improved thermal and pH stability
      compared with its free counterpart. After reusing nine times, it retained 70% of
      the initial activity. Besides, the PGA@IO retained high activity during the
      hydrolysis reactions in continuous catalysis in packed-bed reactor (PBR) after 15
      days.

PMID- 27871383
TI  - Allosteric properties of Geobacillus maltogenic amylase.
AB  - Maltogenic amylases (MAases, EC 3.2.1.133) have been gotten much attention due to
      their various applications in industry and commercial processes. MAases belong to
      subfamily 20 of glycoside hydrolase family 13 (NPase or CDases subfamily) and
      they have important differences with other members of the family. This enzyme
      consists of two subunits which form two active sites in the dimer form by binding
      of the central domain of each subunit to the N domain of the next one (domain
      swapping dimeric structure). Allosterism is a possible way of regulating
      enzymatic activity and no evidence has been found regarding to the cooperativity
      and correlation between MAases subunits, therefore in this study the allosteric
      behavior of MAases from a native strain (Geobacillus sp. Gh6) was investigated.
      Unlike other members of alpha-amylase family, MAases showed positive
      cooperativity between their subunits and the enzyme exhibited sigmoidal nature
      towards all three cyclodextrin (CD) substrates with a Hill constant (nH) value
      equal to 2, 1.6 and 1.1 for alpha-CD, beta-CD and gamma-CD, respectively. On
      further analysis, the effect of glucose and maltose as MAases allosteric
      effectors in the presence of beta-CD substrate showed that these two effectors
      had a biphasic effect; while they stimulated the enzyme activity at low
      concentrations (with a decrease in Hill constant), these metabolites acted as
      allosteric inhibitors at higher concentrations. Due to the key role of MAases in
      carbohydrate metabolization, an efficient regulating system for this enzyme is
      required. In this experiment, for the first time the allosteric properties of
      MAases were observed and investigated.

PMID- 27871385
TI  - Surface charge modification increases firefly luciferase rigidity without
      alteration in bioluminescence spectra.
AB  - Protein engineering can provide useful approaches for loop anchoring and mutation
      of surface-exposed loop residues to Arg for the design of thermostable proteins.
      In this context and due to the high proportion of surface loops, some of the
      solvent-exposed residues in the Lampyris turkestanicus luciferase were mutated to
      Arg. Using the red-emitter mutant luciferase (E354R/Arg356), the single (-Q35R, 
      I182R, -I232R and -L300R), double (-Q35R/I232R) and triple (-Q35R/I232R/I182R)
      mutant luciferases were introduced. The relative remaining activity of -I232R,
      double and triple mutants increased significantly compared to the wild-type at 40
      degrees C. The optimal temperature of these mutants increased up to 40 degrees C
      which were 15 degrees C more than wild-type luciferase. It is anticipated that
      these mutations increased the local interactions that finally improved the
      thermostability and optimum temperature of luciferase. It should be noted that
      Arg substitution at amino acid positions 35, 182 and 232 had no effect on the
      bioluminescence emission spectra. Furthermore, these mutations have not
      significantly changed the specific activities of firefly luciferases. Finally,
      with the use of the homology modeling and molecular docking, the effects of these
      substitutions were evaluated. In conclusion, this study provides beneficial
      insights on how the thermal stability of luciferase can be improved by protein
      engineering for biological applications.

PMID- 27871386
TI  - Super RLuc8: A novel engineered Renilla luciferase with a red-shifted spectrum
      and stable light emission.
AB  - Renilla luciferase is a bioluminescent enzyme which is broadly used as a reporter
      protein in molecular biosensors. In this study, a novel luciferase with desired
      light emission wavelength and thermostability is reported. The results indicated
      that the new luciferase, namely super RLuc8, had a red-shifted spectrum and
      showed stable light emission. Super RLuc8 showed a 10-fold (p-value=0.0084)
      increase in the thermostability at 37 degrees C after 20min incubation, in
      comparison to the native enzyme. The optimum temperature of the mutant increased
      from 30 to 37 degrees C. Molecular dynamics simulation analysis indicated that
      the increased thermostability was most probably caused by a better structural
      compactness and more local rigidity in the regions out of the emitter site.

PMID- 27871387
TI  - Mediator-free interaction of glucose oxidase, as model enzyme for immobilization,
      with Al-doped and undoped ZnO thin films laser-deposited on polycarbonate
      supports.
AB  - Al doped and undoped ZnO thin films were deposited by pulsed-laser deposition on
      polycarbonate sheets. The films were characterized by optical transmission, Hall
      effect measurement, XRD and SEM. Optical transmission and surface reflectometry
      studies showed good transparency with thicknesses ~100nm and surface roughness of
      10nm. Hall effect measurements showed that the sheet carrier concentration was 
      1.44*1015cm-2 for AZO and -6*1014cm-2 for ZnO. The films were then modified by
      drop-casting glucose oxidase (GOx) without the use of any mediators. Higher
      protein concentration was observed on ZnO as compared to AZO with higher specific
      activity for ZnO (0.042Umg-1) compared to AZO (0.032Umg-1), and was in agreement
      with cyclic voltemmetry (CV). X-ray photoelectron spectroscopy (XPS) suggested
      that the protein was bound by dipole interactions between AZO lattice oxygen and
      the amino group of the enzyme. Chronoamperometry showed sensitivity of 5.5MUAmM
      1cm-2 towards glucose for GOx/AZO and 2.2MUAmM-1cm-2 for GOx/ZnO. The limit of
      detection (LoD) was 167MUM of glucose for GOx/AZO, as compared to 360MUM for
      GOx/ZnO. The linearity was 0.28-28mM for GOx/AZO whereas it was 0.6-28mM for
      GOx/ZnO with a response time of 10s. Possibly due to higher enzyme loading, the
      decrease of impedance in presence of glucose was larger for GOx/ZnO as compared
      to GOx/AZO in electrochemical impedance spectroscopy (EIS). Analyses with
      clinical blood serum samples showed that the systems had good reproducibility and
      accuracy. The characteristics of novel ZnO and AZO thin films with GOx as a model
      enzyme, should prove useful for the future fabrication of inexpensive, highly
      sensitive, disposable electrochemical biosensors for high throughput diagnostics.

PMID- 27871388
TI  - The family 22 carbohydrate-binding module of bifunctional xylanase/beta-glucanase
      Xyn10E from Paenibacillus curdlanolyticus B-6 has an important role in
      lignocellulose degradation.
AB  - A newly isolated endo-beta-1,4-xylanase (Xyn10E) from Paenibacillus
      curdlanolyticus B-6 has a modular structure consisting of a family 22
      carbohydrate-binding module (CBM), a glycoside hydrolase (GH) family 10 catalytic
      domain, two fibronectin type III (Fn3) domains, and a family 3 CBM at the C
      terminus. Intact Xyn10E (rXyn10E), CBM22-deleted Xyn10E (X-CBM3), CBM3-deleted
      Xyn10E (X-CBM22), and GH10 catalytic domain only (X-GH10) were expressed in
      Escherichia coli. rXyn10E showed bifunctional degradation activity toward xylan
      and beta-glucan and also degraded microcrystalline cellulose. Although X-CBM3 and
      X-GH10 had drastically reduced xylanase and beta-glucanase activities, X-CBM22
      mostly retained these activities. Similar Km values were obtained for rXyn10E and
      X-CBM3, but kcat and kcat/Km values for X-CBM3 and X-GH10 were lower than those
      for rXyn10E, suggesting that CBM22 of Xyn10E may contribute to catalytic
      efficiency. In binding assays, X-CBM3 was still able to bind to beta-glucan,
      soluble xylan, insoluble xylan, and cellulose through GH10 and CBM3. These
      results indicate that CBM22 has an important role not only in binding to xylan
      and beta-glucan but also in feeding both polysaccharides into the neighboring
      GH10 catalytic domain. rXyn10E showed remarkable synergism with rXyn11A, a major
      xylanase subunit of P. curdlanolyticus B-6, in the degradation of untreated corn
      stover and sugarcane bagasse; however, the combination of X-CBM3 and rXyn11A was
      not synergistic. These results indicate that Xyn10E and Xyn11A act
      synergistically on lignocellulosic biomass, and CBM22 is essential for efficient
      degradation of lignocellulosic materials.

PMID- 27871389
TI  - Activity control of autodisplayed proteins on the same outer membrane layer of E.
      coli by using Z-domain/streptavidin/and lipase/foldase systems.
AB  - The autodisplay technology has been applied for expression of a desired protein
      on the outer membrane (OM) of Escherichia coli. In this work, the OM fractions of
      E. coli with two autodisplayed proteins were separately prepared and mixed to
      demonstrate the feasibility of control over the ratio of two autodisplayed
      proteins. As the first model, Z-domain and streptavidin were autodisplayed, and
      their activities were tested by means of the combined OM layer in a 96-well
      microplate and a surface plasmon resonance (SPR) biosensor. As the second model,
      lipase and foldase were autodisplayed which required an interaction between two
      proteins to obtain the activity of lipase. The OM fractions of E. coli with an
      autodisplayed lipase and foldase were separately prepared and mixed to
      demonstrate the feasibility of control over the ratio of two autodisplayed
      proteins when the interaction of two proteins is required within the same OM
      layer for the activity of the lipase.

PMID- 27871391
TI  - Trying to Understand Nonarteritic Anterior Ischemic Optic Neuropathy through Big
      Data.

PMID- 27871390
TI  - Eco-friendly intracellular biosynthesis of CdS quantum dots without changing
      Escherichia coli's antibiotic resistance.
AB  - In the paper, a green and efficient biosynthetical technique was reported for
      preparing cadmium sulfide (CdS) quantum dots, in which Escherichia coli (E. coli)
      was chosen as a biomatrix. Fluorescence emission spectra and fluorescent
      microscopic photographs revealed that as-produced CdS quantum dots had an optimum
      fluorescence emission peak located at 470nm and emitted a blue-green fluorescence
      under ultraviolet excitation. After extracted from bacterial cells and located
      the nanocrystals' foci in vivo, the CdS quantum dots showed a uniform size
      distribution by transmission electron microscope. Through the systematical
      investigation of the biosynthetic conditions, including culture medium
      replacement, input time point of cadmium source, working concentrations of raw
      inorganic ions, and co-cultured time spans of bacteria and metal ions in the bio
      manufacture, the results revealed that CdS quantum dots with the strongest
      fluorescence emission were successfully prepared when E. coli cells were in
      stationary phase, with the replacement of culture medium and following the
      incubation with 1.0*10-3mol/L cadmium source for 2 days. Results of antimicrobial
      susceptibility testing indicated that the sensitivities to eight types of
      antibiotics of E. coli were barely changed before and after CdS quantum dots were
      prepared in the mild temperature environment, though a slight fall of antibiotic
      resistance could be observed, suggesting hinted the proposed technique of
      producing quantum dots is a promising environmentally low-risk protocol.

PMID- 27871392
TI  - Carol Shields, MD.

PMID- 27871393
TI  - Neglected Choroidal Melanoma Tracking Along Optic Nerve to Brain.

PMID- 27871394
TI  - Atypical Presentation of IgG4-Related Disease of the Eyelid.

PMID- 27871395
TI  - Bilateral Scleritis and Retinal Vasculitis in Microscopic Polyangiitis.

PMID- 27871396
TI  - Vitreous Invasion: Neovascular Frond in Proliferative Diabetic Retinopathy.

PMID- 27871398
TI  - Corrigendum.

PMID- 27871397
TI  - Corrigendum.

PMID- 27871399
TI  - Reply.

PMID- 27871400
TI  - Re: Jabbarvand et al.: Endophthalmitis occurring after cataract surgery outcomes
      of more than 480 000 cataract surgeries, epidemiologic features, and risk factors
      (Ophthalmology 2016;123:295-301).

PMID- 27871401
TI  - Re: Haripriya et al.: Efficacy of intracameral moxifloxacin endophthalmitis
      prophylaxis at Aravind Eye Hospital (Ophthalmology 2016;123:302-308).

PMID- 27871402
TI  - Reply.

PMID- 27871403
TI  - Re: Whitman et al.: Treatment of presbyopia in emmetropes using a shape-changing
      corneal inlay: one-year clinical outcomes (Ophthalmology 2016;123:466-75).

PMID- 27871404
TI  - Reply.

PMID- 27871405
TI  - Re: Slidsborg et al.: Neonatal risk factors for treatment-demanding retinopathy
      of prematurity: a Danish national study (Ophthalmology 2016;123:796-803).

PMID- 27871406
TI  - Reply.

PMID- 27871407
TI  - The Role of Orthobiologics in Fracture Healing and Arthrodesis.
AB  - Nonunion after tibial shaft fracture and hindfoot arthrodesis remains a major
      problem. Known risk factors include advanced age, immunosuppression, smoking, and
      diabetes. Several factors must be considered in the fracture healing process.
      This review evaluates the efficacy of orthobiologics in improving union rates
      after fracture or arthrodesis. Use of compounds have shown increased cellular
      proliferation experimentally. Percutaneous autologous bone marrow has shown
      increased cellular proliferation. Matrix supplementation has shown significant
      improvements in bone healing. Several studies have highlighted the importance of
      adequate graft fill over graft type. Patients at increased risk for nonunion
      would benefit most from these adjuvant therapies.

PMID- 27871408
TI  - The Biology of Bone and Ligament Healing.
AB  - This review describes the normal healing process for bone, ligaments, and
      tendons, including primary and secondary healing as well as bone-to-bone fusion.
      It depicts the important mediators and cell types involved in the inflammatory,
      reparative, and remodeling stages of each healing process. It also describes the
      main challenges for clinicians when trying to repair bone, ligaments, and tendons
      with a specific emphasis on Charcot neuropathy, fifth metatarsal fractures,
      arthrodesis, and tendon sheath and adhesions. Current treatment options and
      research areas are also reviewed.

PMID- 27871410
TI  - Vancouver Experience of Recombinant Human Platelet-Derived Growth Factor.
AB  - Joint arthrodesis utilizing autogenous bone graft remains the gold standard of
      treatment in fusion procedures of the foot and ankle. Graft harvest, however, has
      been associated with increased morbidity to patients as well as increased costs.
      With this in mind, multiple clinical studies have evaluated the efficacy of
      recombinant human platelet-derived growth factor (rh-PDGF-BB) with beta
      tricalcium phosphate (B-TCP) to augment in foot and ankle arthrodesis with
      favorable results. These factors have led to the increased use of rh-PDGF-BB with
      B-TCP in Vancouver with good clinical results.

PMID- 27871409
TI  - The Efficacy of Platelet-Derived Growth Factor as a Bone-Stimulating Agent.
AB  - Nonunion remains the most impactful complication following ankle and hindfoot
      arthrodesis. Historically, surgeons have relied on autologous bone graft (ABG) to
      combat nonunion risk. Although effective, ABG remains limited in quantity, varies
      in quality, and can be associated with harvest site pain and morbidity. Use of
      alternative bone-stimulating agents, however, avoids harvesting an autograft, and
      provides a more predictable dose-response efficacy. This article highlights
      findings from basic science, animal, and human clinical research that led to the
      approval of Augment Bone Graft. We present an adaptation of the surgical
      techniques described for investigators participating in the pivotal trial.

PMID- 27871411
TI  - Injectable Recombinant Human Platelet-derived Growth Factor in Collagen Carrier
      for Hindfoot Fusion.
AB  - Arthrodesis of the hindfoot is a common procedure for degenerative joint disease
      and/or severe deformity. Nonunion is a common complication from this procedure,
      causing an increased burden to the patient and health care system, often
      resulting in the need for revision surgery. Recombinant human platelet-derived
      growth factor (rhPDGF) has been shown to be a safe and effective tool to enhance
      arthrodesis rates in hindfoot surgery while avoiding the potential morbidity of
      bone grafting. This article provides a review of the role of rhPDGF in hindfoot
      fusions, and the surgical technique for performing an rhPDGF enhanced double
      arthrodesis through a medial approach.

PMID- 27871412
TI  - Role of Recombinant Human Bone Morphogenetic Protein-2 on Hindfoot Arthrodesis.
AB  - Despite advances in understanding bone healing physiology and surgical
      techniques, delayed union and nonunion still occur after the treatment of
      hindfoot arthrodesis. There is increasing appeal of bone morphogenetic proteins
      (BMPs) owing to the innate osteoinductive abilities of BMPs. Effective treatment
      with BMPs has been shown in animal studies. Human clinical studies have also
      shown success. The only study investigating the use of recombinant human BMP
      (rhBMP)-2 in hindfoot arthrodesis found a significant increase in fusion rate.
      Treatment cost effective. Complications from their use remain low. rhBMP-2 is a
      safe and effective bone-healing adjunct in hindfoot arthrodesis surgery.

PMID- 27871413
TI  - B2A Polypeptide in Foot and Ankle Fusion.
AB  - Foot and ankle fusion procedures often incorporate autogenous bone graft to help
      achieve bony union. Pain and morbidity associated with graft harvest have
      resulted in decreased autograft use as alternative bone graft substitutes have
      become available. Recently B2A peptide-coated ceramic granules have been
      developed and investigated. B2A, a bioactive synthetic multi-domain peptide
      acting on bone morphogenetic protein receptors of osteoblast precursor cells,
      amplifies the cell response to bone morphogenetic proteins. Use of B2A-granule
      has the additional benefit of eliminating autogenous bone graft donor site
      morbidity. The surgical technique of subtalar arthrodesis incorporating B2A
      granule is described.

PMID- 27871414
TI  - Orthobiologics in the Foot and Ankle.
AB  - Many allogeneic biologic materials, by themselves or in combination with cells or
      cell products, may be transformative in healing or regeneration of
      musculoskeletal bone and soft tissues. By reconfiguring the size, shape, and
      methods of tissue preparation to improve deliverability and storage, unique
      iterations of traditional tissue scaffolds have emerged. These new iterations,
      combined with new cell technologies, have shaped an exciting platform of
      regenerative products that are effective and provide a bridge to newer and better
      methods of providing care for orthopedic foot and ankle patients.

PMID- 27871415
TI  - Autologous Bone Graft in Foot and Ankle Surgery.
AB  - Bone graft is a common adjunct procedure in orthopedic surgery used for fusions,
      fracture repair, and the reconstruction of skeletal defects in the foot and
      ankle. Autologous graft, or autograft, involves the transport of bone from a
      donor site to another location in the same patient. It is considered by many to
      be the gold standard of bone grafting, as it is provides all biologic factors
      required for functional graft. Further, autograft is 100% histocompatible with no
      risk of disease transmission.

PMID- 27871416
TI  - Bone Marrow Aspirate Concentrate for Bone Healing in Foot and Ankle Surgery.
AB  - Autologous bone marrow aspirate concentrate (BMAC) has become a popular
      orthobiologic to augment bone healing. The potential benefit comes from
      osteoprogenitor cells and growth factors that can lead to new bone formation in
      the setting of foot and ankle arthrodesis procedures. BMAC has an excellent
      safety record and has demonstrated efficacy in animal models of bone healing.
      Although scant, the literature on the use of BMAC in foot and ankle surgery does
      demonstrate promise for this orthobiologic adjuvant.

PMID- 27871417
TI  - Large BM Intra-Articular Allograft.
AB  - Posttraumatic tibiotalar arthritis is a challenging problem in young, active
      patients. Many of these patients do not want to pursue ankle arthrodesis after
      they fail conservative treatment measures, as they wish to preserve joint motion.
      Osteochondral shell allograft arthroplasty has been described as a reasonable
      alternative for treating these patients. The procedure itself is technically
      demanding; however, with improvements in surgical technique and adequate
      preoperative patient counseling, it provides improvement in ankle function and
      has good outcomes for most patients at long-term follow-up.

PMID- 27871419
TI  - The Use of Allostem in Subtalar Fusions.
AB  - Subtalar arthrodesis is the mainstay for treatment of a variety of hindfoot
      problems associated with arthritis, however with an unpredictable if not high
      rate of nonunion. This article covers the use of adipose-derived stem cells as an
      adjunct or alternative to autologous or other bone grafting materials. Promising
      development and encouraging data exist with respect to the use of adipose-derived
      mesenchymal stem cells for bone arthrodesis, which is discussed in more detail in
      the article.

PMID- 27871418
TI  - Efficacy of a Cellular Allogeneic Bone Graft in Foot and Ankle Arthrodesis
      Procedures.
AB  - A cellular allogeneic bone graft can be used in patients at high risk for
      nonunion after arthrodesis surgery. This study explores the utility and efficacy
      of MAP3 in foot and ankle arthrodesis procedures. Map3 is a cellular allogeneic
      bone graft that contains osteogenic, osteoconductive, osteoinductive, and
      angiogenic properties. A total of 23 mostly high-risk patients were included in
      this study. The overall fusion rate was 83%. Univariate analysis demonstrated
      diabetic patients remain at risk of recurrent nonunion (P<.001) despite
      supplementation with MAP3. These data demonstrate successful fusion in high-risk
      patients when MAP3 is used.

PMID- 27871420
TI  - Platelet-Rich Plasma and Concentrated Bone Marrow Aspirate in Surgical Treatment
      for Osteochondral Lesions of the Talus.
AB  - Platelet-rich plasma (PRP) and concentrated bone marrow aspirate (CBMA) have the
      potential to improve the quality of cartilage repair in osteochondral lesions of
      the talus (OLT). In this review, we describe the basic science and clinical
      evidence that has been published on the topic of PRP and CBMA on 2 commonly used
      surgical techniques for the treatment of OLT: bone marrow stimulation and
      osteochondral autograft transfer.

PMID- 27871421
TI  - Mesenchymal Stem Cell-Bearing Sutures for Tendon Repair and Healing in the Foot
      and Ankle.
AB  - Improving the quality and strength of soft tissue repairs remains an important
      area of orthopedic research and innovation. The need for immobilization and early
      motion is an important balance essential for the successful treatment of tendon
      repair and reconstruction. Mesenchymal stem cell (MSC)-bearing sutures represent
      an emerging biological augmentation to traditional suture repair. Two previous
      large studies using stem cell sutures in rat Achilles tendon models have
      demonstrated early increased biomechanical strength and significantly increased
      ultimate failure strength. The MSCs seem to remain locally at the repair site and
      enhance the histologic repair quality of the tendon collagen.

PMID- 27871422
TI  - The Science Behind Wear Testing for Great Toe Implants for Hallux Rigidus.
AB  - Various methods of repairing damaged articular cartilage surfaces have been
      proposed and a variety of implant materials have been tried in an attempt to
      decrease pain and improve function after cartilage repair. The hydrogel made of
      polyvinyl alcohol and saline is a unique material used as an implant in the great
      toe for advanced stage arthritis.

PMID- 27871424
TI  - Orthobiologic in Foot Ankle.

PMID- 27871423
TI  - The Science Behind Surgical Innovations of the Forefoot.
AB  - One of the areas of foot and ankle surgery that has had particular attention over
      the last 5 years has been forefoot surgery. Common procedures include correction
      of the lessor metatarsophalangeal joints and hammertoe deformities, specifically
      metatarsal shortening osteotomies and proximal interphalangeal joint fusions. The
      goals of these surgeries are to improve patient function and allow patients to
      fit into shoes more comfortably in metatarsal shortening and hammertoe.

PMID- 27871425
TI  - [Severe asthma, a priority in respiratory health].

PMID- 27871426
TI  - [LiSSa: An alternative in French to browse health scientific literature ?]

PMID- 27871427
TI  - Increased admission and fasting glucose are associated with unfavorable short
      term outcome after intra-arterial treatment of ischemic stroke in the MR CLEAN
      pretrial cohort.
AB  - BACKGROUND: Limited data are available on the impact of fasting glucose on
      outcome after intra-arterial treatment (IAT). We studied whether hyperglycemia on
      admission and impaired fasting glucose (IFG) are associated with unfavorable
      outcome after IAT in acute ischemic stroke. METHODS: Patients were derived from
      the pretrial registry of the MR CLEAN-trial. Hyperglycemia on admission was
      defined as glucose>7.8mmol/L, IFG as fasting glucose>5.5mmol/L in the first week
      of admission. Primary effect measure was the adjusted common odds ratio (acOR)
      for a shift in the direction of worse outcome on the modified Rankin Scale at
      discharge, estimated with ordinal logistic regression, adjusted for common
      prognostic factors. RESULTS: Of the 335 patients in which glucose on admission
      was available, 86 (26%) were hyperglycemic, 148 of the 240 patients with
      available fasting glucose levels (62%) had IFG. Median admission glucose was
      6.8mmol/L (IQR 6-8). Increased admission glucose (acOR 1.2, 95%CI 1.1-1.3),
      hyperglycemia on admission (acOR 2.6, 95%CI 1.5-4.6) and IFG (acOR 2.8, 95%CI 1.4
      5.6) were associated with worse functional outcome at discharge. CONCLUSION:
      Increased glucose on admission and IFG in the first week after stroke onset are
      associated with unfavorable short-term outcome after IAT of acute ischemic
      stroke.

PMID- 27871428
TI  - Mortality of head injuries in Sub-Saharan African countries: The case of the
      university teaching hospitals of Cameroon.
AB  - BACKGROUND: Reliable data on severe head injury mortality is rarely reported in
      Sub-Saharan African countries and in Cameroon in particular. It was for this
      reason that for the first time ever a prospective study was carried out during a
      one year period in the university hospitals and some selected regional and
      district hospitals in Cameroon. MATERIALS AND METHODS: All the patients admitted
      for head injury in the emergency units of the selected hospitals were enrolled
      and followed up over a period of one month. RESULTS: A total of 2835 consecutive
      patients were included with a sex ratio M/F=3.7/1. One hundred and seventy nine
      (179) patients lost to follow up were not included. The mortality rate was 77% in
      the severe head injury group, 16% in the moderate head injury group and 1% in the
      mild head injury group. In the group of severely injured patients, the mortality
      rates were very high in the academic hospitals (Laquintinie Hospital of Douala,
      General Hospital of Douala, Yaounde Central Hospital, and Yaounde University
      Hospital; 83%, 83%, 81%, and 73% respectively) and in the Regional Hospital of
      Garoua (84%). CONCLUSION: Mortality rates associated with head injury remain very
      high in Cameroon, and this is likely true in many countries across Sub-Saharan
      Africa. The figures approach the mortality expected in the natural history of the
      disease. Strategic plans should be taken at the local and national levels as in
      the case of maternal mortality and HIV infections.

PMID- 27871429
TI  - Novel SACS mutations associated with intellectual disability, epilepsy and
      widespread supratentorial abnormalities.
AB  - We describe eight subjects from two consanguineous families segregating with
      autosomal recessive childhood onset spastic ataxia, peripheral neuropathy and
      intellectual disability. The degree of intellectual disability varied from mild
      to severe and all four affected individuals in one family developed aggressive
      behavior and epilepsy. Using exome sequencing, we identified two novel truncating
      mutations (c.2656C>T (p.Gln886*)) and (c.4756_4760delAATCA (p.Asn1586Tyrfs*3)) in
      the SACS gene responsible for autosomal recessive spastic ataxia of Charlevoix
      Saguenay (ARSACS). MRI revealed typical cerebellar and pontine changes associated
      with ARSACS as well as multiple supratentorial changes in both families as likely
      contributing factors to the cognitive symptoms. Intellectual disability and
      behavioral abnormalities have been reported in some cases of ARSACS but are not a
      part of the characteristic triad of symptoms that includes cerebellar ataxia,
      spasticity and peripheral neuropathy. Our combined findings bring further
      knowledge to the phenotypic spectrum, neurodegenerative changes and genetic
      variability associated with the SACS gene of clinical and diagnostic importance.

PMID- 27871430
TI  - HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP): A
      comparative study to identify factors that influence disease progression.
AB  - OBJECTIVE: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
      can progress slowly or rapidly even though a set of symptoms such as spastic
      paraparesis with pathological reflexes and sweating loss of the lower extremities
      are commonly observed in patients. Although most of the patients are thought to
      be infected to HTLV-1 from their mothers by breast feeding, symptoms of HAM/TSP
      typically manifest in patients later in life (50-60years old in age) and also
      with a higher prevalence of women to men at a ratio of approximately 3:1.
      Probability of developing HAM/TSP and how fast an individual's disease may
      progress from the time of diagnosis could be multifactorial. METHODS: We reviewed
      the records of 150 patients with HAM/TSP admitted to Kagoshima University
      Hospital between 2002 and 2014. Laboratory data of cerebrospinal fluid and serum
      and the clinical measurements including age, age of disease onset, progression
      rate, duration of illness, initial symptoms, Osame's Motor Disability Score were
      evaluated. Rapid disease progression of the disease was defined by deterioration
      of motor disability by >3 grades within 2years. RESULTS: Of 150 HAM/TSP patients
      in our cohort, 114 cases (76%) were females. Patients presenting with rapid
      disease progression are approximately 15years older at the age of onset than
      those with a protracted disease course, and have increased number of cell, and
      elevated levels of protein as well as anti-HTLV-1 antibody titer in the CSF,
      suggesting a more active inflammatory process. There is no significant difference
      in the average values of clinical and laboratory parameters between the sexes.
      Furthermore, there is no apparent correlation between rate of disease progression
      and gender. CONCLUSIONS: Our results suggest that age and virus mediated
      inflammation are correlated with disease phenotypes while additional factors such
      as host or HTLV-1 genetics and gender may influence disease susceptibility.

PMID- 27871431
TI  - Neuropsychological impairment in prodromal Parkinson's disease.

PMID- 27871432
TI  - A novel mutation in PGAP2 gene causes developmental delay, intellectual
      disability, epilepsy and microcephaly in consanguineous Saudi family.
AB  - PGAP2 (Post-GPI Attachment to Proteins 2) gene is involved in lipid remodeling
      steps of Glycosylphosphatidylinositol (GPI)-anchor maturation. At the surface of
      the cell this gene is required for proper expression of GPI-anchored proteins.
      Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive
      disorder usually characterized by severe mental retardation. Mutations in the
      PGAP2 gene cause hyperphosphatasia mental retardation syndrome-3. We have
      identified a large consanguineous family from Saudi origin segregating
      developmental delay, intellectual disability, epilepsy and microcephaly. Whole
      exome sequencing with 100* coverage was performed on two affected siblings of the
      family. Data analysis in the patient revealed a novel missense mutation c.191C>T
      in PGAP2 gene resulting in Alanine to Valine substitution (Ala64Val). The
      mutation was reconfirmed and validated by subsequent Sanger sequencing method.
      The mutation was ruled out in 100 unrelated healthy controls. We suggest that
      this pathogenic mutation disrupts the proper function of the gene proteins
      resulting in the disease state.

PMID- 27871433
TI  - Regional variation in acute stroke care organisation.
AB  - BACKGROUND: Few studies have assessed regional variation in the organisation of
      stroke services, particularly health care resourcing, presence of protocols and
      discharge planning. Our aim was to compare stroke care organisation within middle
      (MIC) and high-income country (HIC) hospitals participating in the Head Position
      in Stroke Trial (HeadPoST). METHODS: HeadPoST is an on-going international
      multicenter crossover cluster-randomized trial of 'sitting-up' versus 'lying
      flat' head positioning in acute stroke. As part of the start-up phase, one stroke
      care organisation questionnaire was completed at each hospital. The World Bank
      gross national income per capita criteria were used for classification. RESULTS:
      94 hospitals from 9 countries completed the questionnaire, 51 corresponding to
      MIC and 43 to HIC. Most participating hospitals had a dedicated stroke care
      unit/ward, with access to diagnostic services and expert stroke physicians, and
      offering intravenous thrombolysis. There was no difference for the presence of a
      dedicated multidisciplinary stroke team, although greater access to a broad
      spectrum of rehabilitation therapists in HIC compared to MIC hospitals was
      observed. Significantly more patients arrived within a 4-h window of symptoms
      onset in HIC hospitals (41 vs. 13%; P<0.001), and a significantly higher
      proportion of acute ischemic stroke patients received intravenous thrombolysis
      (10 vs. 5%; P=0.002) compared to MIC hospitals. CONCLUSIONS: Although all
      hospitals provided advanced care for people with stroke, differences were found
      in stroke care organisation and treatment. Future multilevel analyses aims to
      determine the influence of specific organisational factors on patient outcomes.

PMID- 27871434
TI  - Neural correlates of anxiety symptoms in mild Parkinson's disease: A prospective
      longitudinal voxel-based morphometry study.
AB  - BACKGROUND: Anxiety is prevalent in patients with Parkinson's disease (PD) and
      may affect patients' quality of life. Yet, little is known about the neural basis
      of anxiety in PD, and none have used a longitudinal design. METHODS: 73 patients
      with mild PD were recruited and followed up for 18months. A whole-brain analysis
      was first used to identify brain regions associated with anxiety symptoms,
      followed by a regional analysis focusing on a priori hypothesised regions at
      baseline. A multivariate generalized estimating equations analysis was then
      conducted to determine the longitudinal association between grey matter (GM)
      volumetric changes of these significant regions and changes of anxiety symptoms.
      RESULTS: At baseline, anxiety symptom severity was associated with decreased GM
      volumes in the bilateral precuneus and anterior cingulate cortex (ACC). Over
      18months, increased severity of anxiety symptoms was associated with decreased GM
      volume in the left precuneus and ACC, independent of age, gender, education,
      depressive symptom severity or use of psychiatric medication. CONCLUSIONS: These
      results mainly implicate the precuneus and ACC in the pathogenesis of anxiety in
      PD. We speculate that these structural changes could reflect the disrupted
      default mode network due to PD pathology, contributing to spontaneous anxiety
      related self-focused thoughts.

PMID- 27871435
TI  - Resting-state functional connectivity of subthalamic nucleus in different
      Parkinson's disease phenotypes.
AB  - Previous studies showed that the subthalamic nucleus (STN) plays a crucial role
      in Parkinson's disease (PD) pathophysiology. During rest, PD phenotypes exhibit
      different STN functional connectivity. STN functional connectivity was examined
      in 31 PD patients [12 tremor-dominant (TD) and 19 posture instability gait
      difficulty (PIGD)] and 22 healthy controls (HC). Compared with controls and PIGD
      patients, the TD patients exhibited higher functional connectivity between the
      bilateral STN and the left cerebellar anterior lobe. Compared with the TD and HC
      groups, in the PIGD subgroup functional connectivity was lower between the left
      putamen and the STN, as well as between the pons and the STN. In the PIGD
      subgroup, functional connectivity was greater between the STN and bilateral
      occipital lobe, which positively correlated with PIGD scores in PD patients.
      Additionally, STN-cerebellum connectivity positively correlated with the tremor
      score, and STN-putamen connectivity negatively correlated with the PIGD score in
      PD patients. PD subtypes with distinguished STN functional connectivity might
      explain the various pathophysiological mechanisms in tremor and gait disorders.
      Increased coupling between the STN and cerebellum might underlie the neural
      substrate of PD tremors. Lower functional connectivity between the STN and
      putamen might underpin PD gait and posture disturbances, while higher functional
      connectivity between the STN and visual cortex might play a compensatory role.

PMID- 27871436
TI  - Editor's update and selected articles from the Journal of the Neurological
      Sciences.

PMID- 27871437
TI  - Efficacy of intravenous lidocaine and magnesium in intractable trigeminal
      neuralgia: A preliminary report.

PMID- 27871439
TI  - Corrigendum to "Mortality of advanced Parkinson's disease patients treated with
      deep brain stimulation surgery" [J. Neurol. Sci. 369, 230-235].

PMID- 27871438
TI  - Chewing-induced blepharospasm in Parkinson's disease.

PMID- 27871440
TI  - Investigation and clinical applications of muscle strength change in
      cerebrospinal fluid tap test in cases of idiopathic normal pressure
      hydrocephalus: A retrospective study.
AB  - The cerebrospinal fluid tap test (CSFTT) is widely used to diagnose idiopathic
      normal pressure hydrocephalus (iNPH) and predict the therapeutic effectiveness of
      shunting. However, the ability to walk cannot be quantified for patients who are
      unable to walk. Therefore, we examined whether the iNPH diagnostic aid is
      possible using dynamometry, even for patients who are unable to walk. In this
      study, 45 patients underwent grip strength assessment, quadriceps strength
      assessment, 10-m walk test, and 3-m Timed Up and Go test before and after CSFTT.
      Our investigation of physical functions indicated that the CSFTT-positive group
      demonstrated significant improvements in grip and bilateral quadriceps muscle
      strength. The results of the receiver operating characteristic analysis indicated
      that leg muscle strength measurement reliability was high and that the area under
      the curve was 0.754-0.811. Our investigation of the clinically effective cutoff
      point for the rate of change indicated that it was 13.6% for right quadriceps
      muscle strength and 15.3% for left quadriceps muscle strength. Comparing CSFTT
      results in cases of iNPH with the observed rate of change in muscle strength can
      aid in the diagnosis of iNPH.

PMID- 27871442
TI  - Alternating deep brain stimulation frequencies in Parkinson's disease.

PMID- 27871441
TI  - Daytime sleepiness and nighttime sleep quality across the full spectrum of
      cognitive presentations in essential tremor.
AB  - There is increasing evidence that essential tremor (ET) is a complex and
      heterogeneous disorder with nonmotor features including cognitive deficits and
      sleep problems. We are unaware of a study that has examined sleep deficits in ET
      across the full spectrum of cognitive presentations. Cross-sectional (baseline)
      data on self-reported nighttime sleep dysfunction and excessive daytime
      sleepiness were collected using the Pittsburgh Sleep Quality Index (PSQI) and the
      Epworth Sleepiness Scale (ESS) in 96 ET cases enrolled in a prospective study.
      Cases underwent a comprehensive neuropsychological assessment, and were
      classified as ET with normal cognition (ET-NC), ET with mild cognitive impairment
      (ET-MCI), and ET with dementia (ET-D). PSQI scores did not significantly differ
      across the three ET cognitive groups (p=0.22). ESS scores were highest (more
      daytime sleepiness) in the ET-MCI group, followed by the ET-D and ET-NC groups,
      respectively (p=0.016). We examined sleep dysfunction across the cognitive
      spectrum in ET. We demonstrate for the first time that excessive daytime
      sleepiness is greater in ET-MCI than ET-NC. Unpredicted low ESS scores in the
      dementia group raises two possibilities: a self-report bias related to cognitive
      impairment and/or the possibility that currently undefined pathological
      heterogeneity in ET may map onto multiple presentations of non-motor deficits.

PMID- 27871443
TI  - Infantile-onset ascending spastic paraplegia phenotype associated with SPAST
      mutation.

PMID- 27871444
TI  - Polyneuropathy in levodopa-treated Parkinson's patients.
AB  - Recently published studies show that the prevalence of polyneuropathy (PNP) is
      higher in patients with Parkinson's disease (PD) than in age-matched controls.
      Its pathogenesis, however is a matter of controversy. The major hypothesis is the
      toxicity of high concentrations of homocysteine (Hcy) possibly related to
      levodopa (LD) therapy. The aim of the present study was to determine the
      prevalence of PNP, independent of other etiologies, and to determine the
      relationship to demographic and clinical factors in LD-treated Parkinson's
      patients. A total of 102 patients (51 patients with PD and 51 sex- and age
      matched healthy controls) were enrolled in the study. The presence of any risk
      factors for PNP, ascertained from the history and laboratory tests, was an
      exclusion criterion. The Toronto Clinical Scoring System (TCSS) was used for
      clinical assessment of PNP. The objective assessment was based on
      electroneurography (ENG) studies in which motor nerves (peroneal and tibial
      nerves) as well as sensory nerves (sural and superficial peroneal nerves) were
      bilaterally examined. The severity of the disease was determined using the UPDRS
      scale (Unified Parkinson's Disease Rating Scale) and the Hoehn-Yahr (H-Y) scale.
      In the PD group, the clinical and neurophysiological indicators of PNP,
      manifested as a symmetrical and predominantly sensory axonal neuropathy, were
      more frequent then in the control group and observed in 43.1% vs. 13.7% and 15.7%
      vs. 2% of subjects respectively. The presence of PNP correlated with age and the
      severity of PD. Patients with PD and PNP had a higher level of Hcy as compared to
      PD patients without PNP, however the difference was not statistically
      significant. The frequency of PNP in PD patients is higher than in controls. The
      characteristics and discrepancy between the number of patients with clinical and
      ENG detected PNP may suggest the small fiber neuropathy (SFN) as the dominant
      form of neuropathy in PD patients.

PMID- 27871445
TI  - Neuro-Sweet disease: A diagnostic challenge.

PMID- 27871446
TI  - Hemichorea improvement following endarterectomy for internal carotid artery
      stenosis.

PMID- 27871447
TI  - Novel compound heterozygous mutations in a child with Ataxia-Telangiectasia
      showing unrelated cerebellar disorders.
AB  - We report the case of a 6-year-old female patient with Ataxia Telangiectasia, an
      extremely rare condition, who developed in addition a left cerebellar astrocytoma
      and a right cerebellar infarction, considered as two independent events. Children
      with AT have an increased risk of developing cancer, but only few cases of glioma
      are reported and, at our knowledge, no other case of unrelated cerebellar glioma
      and cerebellar infarction in with the same AT patient have been described. The
      molecular analysis of ATM (Ataxia Telangiectasia Mutated) gene showed that the
      patient is compound heterozygote for two previously unreported mutations:
      c.3291delC (p.Phe1097fs) at exon 25 and c.8198A>C (p.Gln2733Pro) at exon 58. The
      role of the identified ATM gene mutations in the pathogenesis of Ataxia
      Telangiectasia and the coexisting cerebellar disorders is discussed.

PMID- 27871448
TI  - Diagnostic and prognostic value of serum vitronectin levels in human glioma.
AB  - OBJECTIVE: Vitronectin is an extracellular matrix protein, the synthesis of which
      by glioma cells correlates with tumor grade. The current study was designed to
      investigate the relationship between serum vitronectin levels and
      clinicopathological characteristics, diagnosis and prognosis in glioma patients.
      METHODS: In a prospective observatory study, a total of 98 glioma patients, 98
      healthy controls, 98 other non-glioma brain tumors, and 98 other non-tumor
      neurological diseases were recruited. Following univariate analyses, multivariate
      analyses were performed to explore the associations of serum vitronectin levels
      with survival and clinicopathological parameters. Receiver operating
      characteristic curve analysis was done to assess its diagnostic and prognostic
      predictive value. RESULTS: Serum vitronectin levels were significantly elevated
      in glioma patients as compared with other groups. High Wealth Health Organization
      grade was independently associated with high vitronectin levels. Serum
      vitronectin levels could significantly distinguish glioma patients from other
      groups and discriminate high-grade glioma from low-grade glioma. Vitronectin
      levels markedly predicted 5-year progression and 5-year mortality. Moreover,
      serum vitronectin was identified as an independent predictor for 5-year overall
      survival and 5-year progression-free survival as well as 5-year mortality and 5
      year progression. CONCLUSION: Serum vitronectin may be a promising diagnostic and
      prognostic biomarker that can be detected in the peripheral blood of patients
      with glioma.

PMID- 27871450
TI  - Chronic inflammatory demyelinating polyneuropathy associated with Rickettsia
      conorii: First case report.

PMID- 27871449
TI  - Botulinum toxin as early intervention for spasticity after stroke or non
      progressive brain lesion: A meta-analysis.
AB  - Spasticity is a functionally limiting disorder that commonly occurs following
      stroke or severe brain injury, and may lead to disability and pain. In tandem
      with neurorehabilitation, botulinum toxin type A (BoNT-A) is the recommended
      first-line treatment for spasticity and, to date, the majority of trials have
      reported BoNT-A use in patients >6months after ictus. The present meta-analysis
      aimed to evaluate the effects of early BoNT-A injection for post-stroke
      spasticity on improvements in hypertonicity, disability, function and associated
      pain. A literature search yielded six studies reporting the effects of BoNT-A
      treatment within 3months post-stroke; three in the upper limb and three in the
      lower limb. All six studies permitted concomitant rehabilitation. Reduction in
      hypertonicity was compared in all six studies and revealed a significant
      treatment effect (P=0.0002) on the most affected joints between weeks 4 and 12
      following injection. However, no significant effects of treatment were observed
      for improvement in disability at week 4 or improvement in function at weeks 4 and
      20-24. A trend towards reduction in spasticity-related pain at week 4 following
      BoNT-A treatment (P=0.13) was also observed. These results demonstrate the
      beneficial effects of BoNT-A treatment on improving hypertonicity within 3months
      post-stroke and emphasise the importance of concomitant neurorehabilitation
      therapy.

PMID- 27871451
TI  - Aneurysm rebleeding after poor-grade aneurysmal subarachnoid hemorrhage:
      Predictors and impact on clinical outcomes.
AB  - BACKGROUND: Aneurysm rebleeding is a major cause of morbidity and mortality after
      aneurysmal subarachnoid hemorrhage (aSAH) and more often occurs in patients with
      poor-grade aSAH. Limited data on predictors of rebleeding in these patients are
      available. OBJECTIVE: To investigate predictors of aneurysm rebleeding after poor
      grade aSAH and the association of rebleeding with clinical outcomes. METHODS: A
      multicenter poor-grade aneurysm study was a prospective and observational
      registry of consecutive patients who presented with poor-grade aSAH defined as a
      World Federation of Neurosurgical Societies (WFNS) grade of IV or V. Rebleeding
      was defined as a new hemorrhage on computed tomography scan. Clinical outcomes
      were assessed with modified Rankin score. Multivariate logistic regression
      analyses were used to determine independent predictors of rebleeding and
      association between the rebleeding and clinical outcomes at 12months. RESULTS: Of
      the 297 patients included in this study, 30 (10.1%) patients experienced
      rebleeding. Most rebleeding occurred within 24h after ictus. 22 (73.3%) patients
      died at discharge. Aneurysm rebleeding was independently associated with poor
      outcome (odds ratio [OR] 36.37, p<0.001) and associated with mortality (OR 25.03,
      p<0.001) at 12months. The multivariate analysis showed that a lower Fisher grade
      (OR 0.49, 95% CI 0.31-0.77; p=0.002), ruptured anterior cerebral artery aneurysms
      (OR 4.26, 95% CI 1.07-16.90; p=0.039), external ventricular drainage (OR 4.62,
      95% CI 1.46-14.59; p=0.009) were independently associated with aneurysm
      rebleeding. CONCLUSIONS: The outcome of aneurysm rebleeding remains very poor. A
      lower Fisher grade, ruptured anterior cerebral artery aneurysms, external
      ventricular drainage were associated with increased risk of rebleeding.

PMID- 27871452
TI  - Galectin-3 is not an outcome biomarker in ischemic stroke. Letter concerning the
      study 'Role of galectin-3 in plasma as a predictive biomarker of outcome after
      acute intracerebral hemorrhage.

PMID- 27871453
TI  - Chasing dizzy chimera: Diagnosis of combined peripheral and central
      vestibulopathy.
AB  - Diagnosis of combined peripheral and central vestibulopathy remains a challenge
      since the findings from peripheral vestibular involvements may overshadow those
      from central vestibular disorders or vice versa. The aim of this study was to
      enhance detection of these intriguing disorders by characterizing the clinical
      features and underlying etiologies. We had recruited 55 patients with combined
      peripheral and central vestibulopathy at the Dizziness Clinic of Seoul National
      University Bundang Hospital from 2003 to 2013. Peripheral vestibular involvement
      was determined by decreased caloric responses in either ear, and central
      vestibulopathy was diagnosed with obvious central vestibular signs or the lesions
      documented on MRIs to involve the central vestibular structures. Combined
      peripheral and central vestibulopathy could be classified into four types
      according to the patterns of vestibular presentation. Infarctions were the most
      common cause of acute unilateral cases while cerebellopontine angle tumors were
      mostly found in chronic unilateral ones. Wernicke encephalopathy and degenerative
      disorders were common in acute and chronic bilateral disorders. Twenty five
      (45.5%) patients showed only vestibular findings with or without auditory
      involvements, but association with gaze-evoked nystagmus, impaired smooth pursuit
      or central types of head shaking nystagmus indicated a central vestibular
      involvement in most of them (23/25, 92.0%). Given the requirements for urgent
      treatments and potentially grave prognosis of combined vestibulopathy, central
      signs should be sought even in patients with clinical or laboratory features of
      peripheral vestibulopathy. Scrutinized bedside evaluation, however, secured the
      diagnosis in almost all the patients with combined vestibulopathy.

PMID- 27871454
TI  - Body mass index and interferon-beta efficacy (and safety) in multiple sclerosis.

PMID- 27871455
TI  - Episodic ataxia and SCA6 within the same family due to the D302N CACNA1A gene
      mutation.
AB  - Several dominant mutations of CACNA1A gene were associated with at least three
      different allelic disorders: spino-cerebellar ataxia type 6 (SCA6), episodic
      ataxia type 2 (EA2), and familial hemiplegic migraine-1 (FHM1). It is generally
      thought that loss-of-function mutations are associated with EA2, gain-of-function
      missense mutations with FHM1, and abnormal CAG expansions with SCA6. But,
      overlapping features, atypical symptoms and co-occurrence of distinct phenotypes
      within the same family were reported. We describe a four generation family
      showing different phenotypes ranging from EA2 to SCA6 and carrying the p.D302N
      CACNA1A gene mutation. In our family the phenotypes maintained separate and
      gender differences corresponding to different phenotypes were observed.

PMID- 27871456
TI  - A prognostic factor in focal hand dystonia: typist's cramp cases and literature
      review.
AB  - The prognosis of focal hand dystonia (FHD) remains unclear. We retrospectively
      studied six patients with typist's cramp in our hospitals, and five cases in the
      PubMed database. All of them were right-handed. We compared clinical features
      between simple (dystonia in only one specific task), and dystonic/progressive
      groups (dystonia in several and/or new tasks). The initially affected right hand
      ratio was significantly higher in dystonic/progressive groups than in simple
      group (p=0.015). Initially affected hand may be a predictor for the progression,
      implying that the progression may be associated with the amount of daily routine
      hand movements.

PMID- 27871457
TI  - Minocycline is effective in intracerebral hemorrhage by inhibition of apoptosis
      and autophagy.
AB  - BACKGROUND: Intracerebral hemorrhage is the least treatable type of stroke and
      affects millions of people worldwide. Treatment for ICH varies from medicine to
      surgery, but the rate of mortality and mobility still remains high. Minocycline
      is a tetracycline antibiotic increasingly recognized for its neuroprotective
      potential. In earlier studies, we demonstrated that many secondary injuries
      caused by ICH could be significantly reduced by injection of minocycline in rat
      models. The following research investigates the role of minocycline in reducing
      brain injury. METHODS: Twenty-four rats were administered 100MUl autologous
      arterial blood injections into the right basal ganglia, treated with minocycline
      or vehicle and euthanized on the 1st, 3rd, and 7th day. Immunohistochemistry,
      TUNEL, and western blot analysis were performed to analyze the effects of
      minocycline on apoptosis and autophagy. RESULTS: After the injection of
      minocycline, TUNEL-positive cells were remarkably reduced on days 1, 3 and 7;
      Beclin-1, LC3BII/I, caspase-3/8 were all suppressed after treatment. The
      relationship between Cathepsin D and minocycline remained unknown. CONCLUSIONS:
      Our studies suggest the potential medicinal value of minocycline, through both
      anti-autophagy and anti-apoptosis pathways.

PMID- 27871459
TI  - Morphology, histochemistry and glycosylation of the placenta and associated
      tissues in the European hedgehog (Erinaceus europaeus).
AB  - INTRODUCTION: There are few descriptions of the placenta and associated tissues
      of the European hedgehog (Erinaceus europaeus) and here we present findings on a
      near-term pregnant specimen. METHODS: Tissues were examined grossly and then
      formalin fixed and wax-embedded for histology and immunocytochemistry
      (cytokeratin) and resin embedded for lectin histochemistry. RESULTS: Each of four
      well-developed and near term hoglets displayed a discoid, haemochorial placenta
      with typical labyrinth and spongy zones. In addition there was a paraplacenta
      incorporating Reichert's membrane and a largely detached yolk sac. The
      trophoblast of the placenta contained diverse populations of granule which
      expressed most classes of glycan. Intercellular membranes were also glycosylated
      and this tended to be heavier in the labyrinth zone. Fetal capillary endothelium
      had glycosylated apical surfaces expressing sialic acid and various other
      glycans. Glycogen was present in large cells situated between the spongy zone and
      the endometrium. Trophoblast cells in the placental disc and under Reichert's
      membrane, as well as yolk sac endoderm and mesothelium, were cytokeratin
      positive. Reichert's membrane was heavily glycosylated. Yolk sac inner and outer
      endoderm expressed similar glycans except for N-acetylgalactosamine residues in
      endodermal acini. DISCUSSION: New features of near-term hedgehog placenta and
      associated tissues are presented, including their glycosylation, and novel yolk
      sac acinar structures are described. The trophoblast of the placental disc showed
      significant differences from that underlying Reichert's membrane while the glycan
      composition of the membrane itself showed some similarity to that of rat thereby
      implying a degree of biochemical conservation of this structure.

PMID- 27871458
TI  - Eligibility for mechanical thrombectomy in acute ischemic stroke: A phase IV
      multi-center screening log registry.
AB  - No eligibility screening logs were kept in recent mechanical thrombectomy (MT)
      RCTs establishing safety and efficacy of endovascular reperfusion therapies for
      acute ischemic stroke (AIS). We sought to evaluate the potential eligibility for
      MT among consecutive AIS patients in a prospective international multicenter
      study. We prospectively evaluated consecutive AIS patients admitted in four
      tertiary-care stroke centers during a twelve-month period. Potential eligibility
      for MT was evaluated using inclusion criteria from MR CLEAN & REVASCAT. Our study
      population consisted of 1464 AIS patients (mean age 67+/-14years, 56% men, median
      admission NIHSS-score: 5, IQR: 3-10). A total of 123 (8%, 95% CI: 7%-10%) and 82
      (6%, 95% CI: 5%-7%) patients fulfilled the inclusion criteria for MR
      CLEAN&REVASCAT respectively. No evidence of heterogeneity (p>0.100) was found in
      the eligibility for MT across the participating centers. Absence of proximal
      intracranial occlusion (69%) and hospital arrival outside the eligible time
      window (38% for MR CLEAN & 35% for REVASCAT) were the two most common reasons for
      ineligibility for MT. Our everyday clinical practice experience suggests that
      approximately one out of thirteen to seventeen consecutive AIS may be eligible
      for MT if inclusion criteria for MR CLEAN and REVASCAT are strictly adhered to.

PMID- 27871460
TI  - Placental histological lesions in fetal and neonatal alloimmune thrombocytopenia:
      A retrospective cohort study of 21 cases.
AB  - BACKGROUND: Alloimmunization against human platelet antigens (HPAs) can occur
      prenatally and induce fetal/neonatal alloimmune thrombocytopenia (FNAIT). The aim
      of this study was to identify placental histological features associated with
      platelet alloimmunization and their clinical significance. METHODS: This study
      examined 21 placentas from FNAIT-affected pregnancies and 42 age-matched control
      cases, all collected from pathology departments in the Rhone-Alpes region.
      Clinical and laboratory findings were collected for each FNAIT case. Two
      pathologists reviewed the placental slides of each FNAIT and control case.
      Histological features, with special emphasis on chronic inflammatory lesions,
      were evaluated. Differences between the two groups were calculated with odds
      ratios (ORs) and assessed with Wald's chi-square. RESULTS: FNAIT was associated
      with a significantly higher frequency of chronic chorioamnionitis (CC) (OR 14,
      95%CI 1.7-113.8), basal chronic villitis (BCV) (OR 17, 95%CI 2-145.6) and chronic
      intervillositis (CIV). Chronic villitis (CV) (OR 3.7, 95%CI 0.9-15.2) and chronic
      deciduitis (CD) (OR 4.7, 95%CI 0.79-28.2) were also more frequent in the FNAIT
      than the control group, but these differences were not statistically significant.
      CONCLUSIONS: FNAIT is significantly associated with CC, BCV, and CIV. This
      chronic inflammatory reaction is preferentially localized on the maternofetal
      interface. Anti-HPA alloimmunization may trigger an immunological conflict
      similar to graft-versus-host disease.

PMID- 27871461
TI  - Nuclear factor of activated T-cells (NFAT) regulates soluble fms-like tyrosine
      kinase-1 secretion (sFlt-1) from human placenta.
AB  - INTRODUCTION: Preeclampsia is a serious complication affecting 5-8% of
      pregnancies. Central to its pathogenesis is placental hypoxia and inflammation
      which leads to secretion of soluble fms-like tyrosine kinase 1 (sFlt-1). sFlt-1
      causes widespread endothelial dysfunction. The molecular mechanisms regulating
      sFlt-1 production remain poorly understood. Recently, a binding site for the
      nuclear factor activated T cells (NFAT) transcription factor has been found on
      fms-like tyrosine kinase 1 (FLT-1) promoter. METHODS: We assessed whether
      inhibiting NFAT impacts FLT-1, sFlt-1 and cytokine expression, as well as sFlt-1
      secretion in primary cytotrophoblasts, placental explants and human umbilical
      vein endothelial cells (HUVECs). We investigated whether NFAT is regulated by
      hypoxia in primary cytotrophoblasts. We characterised the expression of NFAT1-4
      in preterm preeclamptic compared to gestationally matched placentas. RESULTS:
      Inhibiting NFAT reduced FLT-1 and sFlt-1 splice variant e15a transcription,
      concordant with reduced total sFlt-1 and sFlt-1 e15a secretion from primary human
      cytotrophoblasts. This effect appeared tissue specific as inhibiting NFAT did not
      change sFlt-1 secretion from endothelial cells. Inhibiting NFAT also reduced
      transcription of inflammatory cytokines IL-1beta and IL-10 in primary
      cytotrophoblasts. NFAT1 and NFAT3 mRNA expression were significantly increased
      under hypoxia (1% O2). Inhibiting NFAT under hypoxia significantly reduced FLT-1
      and sFlt-1 e15a transcription, but did not reduce sFlt-1 secretion. NFAT mRNA and
      protein localisation was not different in preeclamptic compared to gestationally
      matched placenta. DISCUSSION: NFAT positively regulates placental FLT-1 and sFlt
      1 e15a, secretion of sFlt-1 and inflammatory cytokine expression. It may be
      involved in the pathophysiology of preeclampsia.

PMID- 27871463
TI  - Pattern of adhesive molecules expression in placenta of non-complicated ART
      pregnancies.
AB  - OBJECTIVE: To investigate changes occurring in the morphometric parameters of
      chorionic villi and their vessels as well as in adhesive molecules expression in
      placenta of ART pregnancies. METHODS: Case-control study including a total of 52
      placentas of non-complicated pregnancies of women delivered by spontaneous
      conception (SC) (n = 26) compared with those of ART (n = 26). Histological and
      morphometric assessment of fetal chorionic villi as well as the expression of
      various adhesive molecules (ICAM-1, VCAM-1 and PECAM-1) were performed in fetal
      plasma and placenta. RESULTS: Although we did not observe any obvious changes in
      the histological structure of placenta of ART pregnancies, it showed a
      significant (p < 0.05) decrease in the syncytiotrophoblast cytoplasmic area
      accompanied with a significant increase (p < 0.05) in the vessel area and
      syncytiotrophoblast nuclear area without remarkable change in the total villous
      area or total syncytiotrophoblast % area. In addition, almost all levels of the
      assayed adhesive molecules were significantly increased (p < 0.05) in placenta as
      well as in fetal plasma of ART pregnancies compared with SC. CONCLUSION: We
      suggested in the current study that the altered adhesive molecules expression
      accompanying the increased vessel area and decreased syncytial cytoplasm area may
      indicate a subclinical endothelial stress in placenta of non-complicated ART
      pregnancies.

PMID- 27871462
TI  - Placental expression of DNA methyltransferase 1 (DNMT1): Gender-specific relation
      with human placental growth.
AB  - AIMS: Placental physiology and morphology is critically regulated by DNA
      methylation. As such, placental global DNA methylation and transcript abundance
      of placental DNA methyltransferases (DNMT1 and DNMT3A) may relate to placental
      and fetal growth in human pregnancies. We aimed to test correlations of human
      fetoplacental parameters and birth weight with the placental expression of DNA
      methyltransferases (DNMT1 and DNMT3A) and placental global methylation. SUBJECTS
      AND METHODS: Placentae (n = 109) were collected from small- (SGA) and appropriate
      (AGA) for gestational age full-term singleton pregnancies (n = 56 SGA and 53
      AGA). Placentae and neonates were weighed at birth. Realtime quantitative PCR was
      performed to assess placental transcript abundance of DNMT1, DNMT3A and DNTMT3B
      normalized to a panel of reference genes. LINE-1 methylation was measured using a
      quantitative MethyLight assay in a subset of samples (n = 68). Associations of
      placental transcript abundances of DNMT1, DNMT3A and DNMT3B and of LINE-1
      methylation levels with maternal, placental and neonatal parameters were tested.
      RESULTS: Placental DNMT1 transcript abundance associated positively with
      placental weight (beta = 10.21, P = 0.013). This association was specific to the
      AGA births (beta = 12.77, P = 0.022) and was absent in the SGA births.
      Association of DNMT1 expression with placental weight and birth weight within the
      AGA births was specific to the female gender (Birth weight: beta = 83.61, P =
      0.043; Placental weight: beta = 23.92, P = 0.025). Placental DNMT1 transcript
      levels were not different according to SGA status or gender. Placental DNMT3A
      transcript levels and LINE-1 methylation levels did not show any associations
      with maternal, placental and neonatal parameters. CONCLUSIONS: Placental DNMT1
      expression was found to be associated positively with placental weight and birth
      weight, specifically in the female AGA births. Thus, we hypothesize that
      placental DNMT1 participates in fetoplacental growth in a fetal gender-specific
      manner.

PMID- 27871464
TI  - Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of
      implantation site intermediate trophoblast cells by targeting MCL1.
AB  - OBJECTIVE: Placenta accreta is defined as abnormal adhesion of placental villi to
      the uterine myometrium. Although this condition has become more common as a
      result of the increasing rate of cesarean sections, the underlying causative
      mechanism(s) remain elusive. Because microRNA-29a/b/c (miR-29a/b/c) have been
      shown to play important roles in placental development, this study evaluated the
      roles of these microRNAs in placenta accreta. METHODS: Expression of miR-29a/b/c
      and myeloid cell leukemia-1 (MCL1) were quantified in patient tissues and
      HTR8/SVneo trophoblast cells using the real-time quantitative polymerase chain
      reaction. Western blotting was used to analyze expression of the MCL1 protein in
      HTR8/SVneo trophoblast cells with altered expression of miR-29a/b/c. To determine
      their role in apoptosis, miR-29a/b/c were overexpressed in HTR-8/SVneo cells, and
      levels of apoptosis were analyzed by flow cytometry. Luciferase activity assays
      were used to determine whether MCL1 is a target gene of miR-29a/b/c. RESULTS:
      Expression of miR-29a/b/c was significantly lower in creta sites compared to
      noncreta sites (p = 0.018, 0.041, and 0.022, respectively), but expression of
      MCL1 was upregulated in creta sites (p = 0.039). MCL1 expression was
      significantly downregulated in HTR-8/SVneo cells overexpressing miR-29a/b/c (p =
      0.002, 0.008, and 0.013, respectively). Luciferase activity assays revealed that
      miR-29a/b/c directly target the 3' untranslated region of MCL1 in 293T cells.
      Over-expression of miR-29a/b/c induced apoptosis in the HTR-8/SVneo trophoblast
      cell line. Moreover, histopathological evaluation revealed that the number of
      implantation site intermediate trophoblast (ISIT) cells was increased in creta
      sites and that these cells were positive for MCL1. CONCLUSIONS: Our results
      demonstrate that in placenta accreta, miR-29a/b/c inhibits apoptosis of ISIT
      cells by targeting MCL1. These findings provide new insights into the
      pathogenesis of placenta accreta.

PMID- 27871465
TI  - Identification of genes for normalization of real-time RT-PCR data in placental
      tissues from intrahepatic cholestasis of pregnancy.
AB  - The selection of suitable reference genes is crucial for proper interpretation of
      RT-qPCR data. To date, a systematic screening for reference genes in placental
      tissues from intrahepatic cholestasis of pregnancy (ICP) is missing. Eighteen
      candidate reference genes were investigated to determine their applicability by
      descriptive statistics and published algorithms. HPRT1, YWHAZ and PUM1 were found
      to be the most stable genes and could be used for normalization in gene
      expression study of placentas from ICP. The combination of HPRT1 and YWHAZ is
      sufficient and the use of all three genes should be recommended for an improved
      reliability of normalization.

PMID- 27871466
TI  - Autophagy protects against oxidized low density lipoprotein-mediated inflammation
      associated with preeclampsia.
AB  - INTRODUCTION: Inflammatory responses play an important role in the pathogenesis
      of preeclampsia. Recently, the anti-inflammatory role played by autophagy has
      drawn increasing attention. Our aim was to investigate variations in autophagy in
      preeclampsia and protection against oxidized low-density lipoprotein (oxLDL)
      mediated inflammation by autophagy. METHODS: We used immunohistochemistry,
      immunofluorescence, quantitative real-time PCR, and western blotting to analyze
      the expression of autophagy proteins (beclin-1 and LC3II/LC3I) in preeclampsia
      placentas and in JEG-3 cells treated with oxLDL and rapamycin. RESULTS: We found
      a decreased level of autophagy proteins in preeclampsia placentas, and oxLDL did
      not induce autophagy in JEG-3 cells. Furthermore, when cells were pretreated with
      rapamycin, autophagy was activated and expression of inflammatory factors (tumor
      necrosis factor-alpha and interleukin-6) induced by oxLDL was downregulated.
      CONCLUSION: We conclude that impaired autophagy in preeclampsia has potential to
      decrease trophoblast protection from oxidative and inflammatory stress, thereby
      contributing to the pathogenesis of preeclampsia.

PMID- 27871467
TI  - The Effect of Diabetes and Hypertension on the Placental Permeation of the
      Hydrophilic Drug, Ranitidine.
AB  - INTRODUCTION: Ranitidine is a hydrophilic weak base and an H2-receptor antagonist
      which is commonly used for gastroesophageal reflux, including during pregnancy.
      It has limited placental permeation and can be used as a pre-anesthetic antacid
      to prevent aspiration of acidic stomach contents. Recent studies suggest that
      diabetes and hypertension may influence placental permeation of hydrophilic
      drugs. Thus, this study aimed to investigate the influence of diabetes and
      hypertension on ranitidine's placental permeation in pregnant women. METHODS:
      Forty one pregnant women all scheduled for elective cesarean section entered the
      study: healthy control (n = 15), with hypertension (n = 16) and with gestational
      diabetes (n = 10). All women received 50 mg of ranitidine intravenously. Three
      samples of maternal plasma (after ranitidine application, at delivery and after
      delivery), and two umbilical cord samples (arterial and venous blood) were
      collected and analyzed for ranitidine concentrations. Maternal pharmacokinetic
      parameter were calculated as well as feto:maternal and umbilical cord arterial to
      venous concentration ratios. RESULTS: Ranitidine maternal and umbilical cord
      (arterial and venous) concentrations were similar in all three groups and there
      were no difference between feto:maternal ratios nor volume of distribution,
      clearance and half life between the groups. DISCUSSION: Fetal concentrations are
      dependent on maternal concentrations in healthy and hypertensive women but not in
      diabetic women. Hypertension and diabetes did not affect fetal handling of
      ranitidine. Though hypertension and diabetes did not influence ranitidine
      placental permeation, it appears they altered time needed to achieve unity
      between maternal and fetal plasma.

PMID- 27871469
TI  - Placental telomere length decline with gestational age differs by sex and TERT,
      DNMT1, and DNMT3A DNA methylation.
AB  - INTRODUCTION: Telomere length (TL) has been suggested to be influenced by
      inherited genetic and epigenetic variation, hormonal effects, oxidative stress
      and age. However, the dynamics of TL during in utero development have not been
      well explored. This study investigates the relationship between placental TL and
      sex, gestational age (GA), and DNA methylation (DNAm). Placental TL is further
      evaluated in pregnancies complicated by preeclampsia (PE) and intrauterine growth
      restriction (IUGR), conditions hypothesized to lead to decreased placental TL due
      to increased oxidative stress. METHODS: Average TL in 21 early-onset PE (EOPE),
      18 late-onset PE (LOPE), 9 IUGR, 59 viable and 33 non-viable control placentas
      were measured by qPCR. Of these, 13 control, 20 EOPE, 17 LOPE, and 8 IUGR samples
      were also run on the Illumina 450K array. ANOVA was used to compare TL between
      controls and EOPE, LOPE, and IUGR. Linear regression correcting for GA and sex,
      assessed the association between TL and DNAm in biologically-relevant genes
      (TERC, TERT, DNMT1, DNMT3a, DNMT3b), and array-wide. RESULTS: Male sex and
      increasing GA were associated with shorter placental TL. Correcting for these
      factors, no significant difference in TL was observed between EOPE, LOPE, and
      IUGR placentas compared to controls. Targeted analysis revealed TL was associated
      with DNAm at TERT, DNMT1, and DNMT3a. An array-wide approach found no additional
      sites associated with TL. CONCLUSION: Variability in placental TL is associated
      with alterations in DNAm at TERT, DNMT1, and DNMT3a. Placental TL is not strongly
      influenced by EOPE, LOPE, or IUGR.

PMID- 27871468
TI  - Increased levels of soluble corin in pre-eclampsia and fetal growth restriction.
AB  - Atrial natriuretic peptide is biologically activated by the atrial natriuretic
      peptide-converting enzyme, corin, and has an important role in regulating blood
      pressure. We detected elevated serum corin levels in women with pre-eclampsia.
      Interestingly, the serum corin levels were also found to be elevated in
      pregnancies with a related disorder, unexplained fetal growth restriction (FGR)
      without hypertension, suggesting that this phenomenon is not simply a response to
      maternal hypertension. CORIN mRNA levels were not elevated in placentas from pre
      eclampsia or unexplained FGR cases. Likewise, similar signal intensities were
      found for corin in placental syncytiotrophoblast cells by immunostaining. In
      contrast, corin signals were higher in maternal decidua cells from pre-eclampsia
      and unexplained FGR cases. These data suggest that corin may be upregulated in
      maternal decidua in response to an etiologic pathway that is common to pre
      eclampsia and FGR.

PMID- 27871470
TI  - The function of miR-519d in cell migration, invasion, and proliferation suggests
      a role in early placentation.
AB  - The processes of proliferation, migration, and invasion of extravillous
      trophoblasts are critical for placental implantation and early development, and
      directly influence pregnancy outcome. Dysregulation of these processes has been
      associated with placental dysfunction, implicated in clinical conditions such as
      preeclampsia and placental accreta. Among diverse microRNA (miRNA) species that
      are expressed in placental trophoblasts, members of the chromosome 19 miRNA
      cluster (C19MC) stand out in their nearly exclusive expression in the placenta.
      Recent research on the function of C19MC miRNAs in normal cell physiology and
      during tumorigenesis identified one C19MC member, miR-519d, as a regulator of
      cell migration, invasion, and interaction with the extracellular matrix. In this
      review, we focus on the function of miR-519d in placental trophoblasts, where miR
      519d regulates cell migration and invasion, and its aberrant expression is
      associated with preeclampsia. In cancer, the function of miR-519d as an oncomiR
      or a tumor-suppressor is dependent upon the tumor type. Further research on the
      biological function and regulation of miR-519d may illuminate previously unknown
      mechanisms that control cell migration and invasion.

PMID- 27871471
TI  - Endocan expression is increased in the placenta from obese women with gestational
      diabetes mellitus.
AB  - INTRODUCTION: Endocan, a member of the proteoglycan family, is involved in a wide
      range of diseases including obesity and diabetes. The aim of this study was to
      determine the effect of (i) maternal obesity and gestational diabetes mellitus
      (GDM) on placental endocan expression; and (ii) endocan knockdown on markers of
      inflammation. METHODS: Endocan mRNA and protein expression was determined in
      human placenta from (i) lean and obese and normal glucose tolerant (NGT) pregnant
      women (n = 10 patients per group); and (ii) women with GDM and BMI-matched NGT
      women (n = 40 patients per group). Primary villous trophoblast cells and HUVECs
      were used to assess the effect of endocan siRNA knockdown on pro-inflammatory
      cytokines. RESULTS: There was no effect of maternal obesity on placental endocan
      expression. Further, endocan expression was not different between lean NGT and
      BMI-matched women with GDM. However, endocan mRNA and protein expression was
      significantly higher in placenta from obese women with GDM when compared to BMI
      matched NGT women. Knockdown of endocan in villous trophoblast cells and HUVECs
      had no effect on infection- or inflammation-induced expression and secretion of
      IL-6, IL-8 and MCP-1. DISCUSSION: Endocan expression is increased in the human
      placenta from obese women with GDM, and in response to pro-inflammatory stimuli.
      Loss-of-function studies in villous trophoblast cells and HUVECs revealed that
      endocan is not directly involved in the genesis or in the expression of pro
      inflammatory cytokines induced by LPS or IL-1beta. Further studies are required
      to elucidate the functional consequences of increased placental endocan
      expression in obese GDM pregnancies.

PMID- 27871472
TI  - An immunohistochemical study of placental syncytiotrophoblasts in neonatal
      hemochromatosis.
AB  - INTRODUCTION: Neonatal hemochromatosis (NH) is a rare neonatal disorder that
      results in liver cirrhosis with hemosiderin deposition in the liver and other
      organs, similarly to hereditary hemochromatosis. Excess iron is transferred from
      the mother to fetus through the placenta in NH. We examined the expression of
      iron metabolism-related substances in placental syncytiotrophoblasts (STB) by
      immunostaining to clarify how the transfer of iron through STB increases in NH.
      METHODS: Immunostaining was performed using formalin-fixed, paraffin-embedded
      sections of placentae from three NH cases, four gestational age-matched controls,
      and, depending on the antibody examined, five to seven full-term controls. The
      reactivity of immunostaining was assessed by averages of scores assigned by 3
      researchers. RESULTS: On the microvillar surface of STB, the reactions of the
      antibodies against transferrin receptor 1 (TFR1), transferrin, ferritin,
      hepcidin, ferroportin, divalent metal transporter-1 (DMT1), hephaestin, and HFE
      were stronger in NH than in controls. In the cytoplasm, the reactions of
      antibodies against TFR1, transferrin, ferritin, hepcidin, DMT1, hephaestin, HFE,
      and ZIP 14 were stronger in NH than in gestational age-matched controls. Among
      these reactions, those of anti-TFR1 antibody on the surface of STB in NH was
      especially marked. DISCUSSION: In the placenta of NH, increases in expressions of
      TFR1, transferrin, and ferritin of which those of TFR1 were especially marked,
      reflect increased iron influx from the mother to fetus. The hepcidin observed on
      the surface and in the cytoplasm of STB of NH is suggested to be from the mother,
      possibly to compensate for the decreased fetal liver-derived hepcidin.

PMID- 27871473
TI  - Placental histology in spontaneous and indicated preterm birth: A case control
      study.
AB  - INTRODUCTION: Placental pathology is an important contributor in preterm birth,
      both spontaneous and indicated. The aim of this study was to describe and compare
      placental histological features of spontaneous preterm birth versus indicated
      preterm birth. METHODS: A case control study was performed at the University
      Medical Center Utrecht. Women with spontaneous or indicated preterm birth (17-37
      weeks of gestation) delivered in 2009 were included. Women with a pregnancy
      complicated by congenital and/or chromosomal abnormalities were excluded.
      Placentas were systematically examined by an expert pathologist blinded for
      pregnancy outcome, except for gestational age. Placental histological
      abnormalities were classified into infectious inflammatory lesions and maternal
      vascular malperfusion lesions and compared between spontaneous and indicated
      preterm birth. Analysis was stratified for immature (17-23+6 weeks), extremely
      (24-27+6 weeks), very (28-31+6 weeks) and moderate/late (32-36+6 weeks) preterm
      birth. RESULTS: We included 233 women, 121 women with spontaneous preterm birth
      and 112 women with indicated preterm birth. Among women with spontaneous
      extremely preterm birth, higher rates of severe chorioamnionitis were found
      (56.0% vs. 0%). Furthermore, a shift from infectious-inflammatory lesions to
      maternal vascular malperfusion lesions was seen after 28 weeks; in women with
      spontaneous very and moderate/late preterm birth, maternal vascular malperfusion
      lesions were the main finding (46.8% and 47.7% respectively). In women with
      indicated preterm birth, maternal vascular malperfusion lesions were most often
      contributing through all gestational age categories. CONCLUSION: Maternal
      vascular malperfusion lesions are most frequent in both spontaneous and indicated
      very and moderate/late preterm birth. In spontaneous extreme preterm birth
      chorioamnionitis is the main finding.

PMID- 27871474
TI  - The relationship between maternal placental growth factor levels and intrapartum
      fetal compromise.
AB  - INTRODUCTION: Whilst some cases of intrapartum fetal compromise are the result of
      unpredictable catastrophic events, the majority arise from an unrecognised
      reduction in feto-placental reserve in otherwise healthy pregnancies. There is
      currently no reliable technique prior to labour that identifies the at-risk
      fetus. We aimed to investigate the relationship between maternal levels of serum
      placental growth factor (PlGF) and intrapartum fetal compromise in term
      pregnancies prior to labour. Secondary outcomes were caesarean delivery for
      intrapartum fetal compromise and adverse neonatal outcomes. METHODS: A blinded,
      prospective, cross sectional study set at Mater Mother's Hospital, Brisbane,
      Australia. Maternal PlGF concentration was assessed fortnightly from 36 weeks
      until delivery in 378 low-risk pregnant women. Antenatal and intrapartum care was
      managed according to local protocols and guidelines, and intrapartum and neonatal
      outcomes were recorded. RESULTS: Pregnancies that developed intrapartum fetal
      compromise had lower PlGF than those that did not. PlGF concentration was also
      lower amongst pregnancies that developed intrapartum fetal heart rate
      abnormalities, were delivered with abnormal cord gases or Apgar <=7 at 5 min.
      Additionally, PlGF levels were lower in pregnancies with an adverse composite
      neonatal outcome. DISCUSSION: Lower maternal PlGF concentration is associated
      with intrapartum fetal compromise and poorer condition of the newborn. Maternal
      PlGF levels may be useful as a component of a risk stratification tool for
      intrapartum fetal compromise in apparently 'low risk' term pregnancies prior to
      labour.

PMID- 27871475
TI  - Villus packing density and lacunarity: Markers of placental efficiency?
AB  - We evaluate, in routine H&E histology slides, villus quantity in a given area
      (villous packing density, VPD) and the pattern or "gappiness" of villous
      distribution (lacunarity), and test for correlations with a proxy for
      fetoplacental metabolic rate, beta calculated as (ln (placental weight)/ln
      (birthweight)) from Kleiber's law [1]. Three ~4.3 mm2 images each were obtained
      from 88 term placentas. Ranges of VPD and lacunarity were each correlated with
      beta (r = 0.31, p = 0.003, r = 0.23, p = 0.03 and respectively). The relationship
      between beta and within-placenta variation in VPD and lacunarity highlights the
      need to study not merely the mean but the variance of villous geometries and
      spatial distributions.

PMID- 27871476
TI  - Steroid sulfatase is increased in the placentas and whole blood of women with
      early-onset preeclampsia.
AB  - INTRODUCTION: Preeclampsia is a serious complication of pregnancy affecting 5% of
      pregnancies. Our team identified 137 genes highly expressed in placenta relative
      to other human tissues. Here, we have explored a role for steroid sulfatase (STS)
      in preeclampsia by characterising STS expression and the functional effects of
      STS on primary placental trophoblasts. METHODS: Characterisation of STS was
      performed on preterm preeclamptic and gestation-matched normotensive preterm
      controls who delivered at <34 weeks gestation. We characterised placental and
      maternal whole blood STS mRNA and placental protein expression via qRT-PCR,
      immunohistochemistry and Western Blot. To assess whether STS is involved in sFlt1
      secretion and syncytialisation, we administered siRNA to silence STS in primary
      trophoblasts before measuring sFlt1 and hCG secretion and E-Cadherin expression.
      RESULTS: A custom array containing 45 placental specific genes identified 10
      genes significantly altered in the placentas of preeclamptic patients relative to
      normotensive gestation-matched controls. Of these genes, qRT-PCR and western blot
      on a larger cohort confirmed that the expression of STS was significantly
      elevated in preeclamptic placentas (n = 44) relative to gestation matched
      controls (n = 26). Given placental RNA leaks in to the maternal circulation, we
      also assessed STS mRNA expression in the whole blood of patients with
      preeclampsia and found it was significantly increased relative to normotensive
      controls. siRNA knockdown of STS in primary trophoblast resulted in a modest but
      significant reduction in sFlt1 secretion, but had no affect on hCG secretion or E
      Cadherin protein expression. DISCUSSION: STS is increased in preeclamptic
      placentas and maternal whole blood. Our data suggests that STS may affect sFlt1
      secretion by regulating sFlt1-i13 transcription, and not via alterations in
      syncytialisation.

PMID- 27871477
TI  - Hypermethylation of AKT2 gene is associated with neural-tube defects in fetus.
AB  - INTRODUCTION: Neural-tube defects (NTDs) are common birth defects of complex
      etiology. Although many studies have confirmed a genetic component, the exact
      mechanism between DNA methylation and NTDs remains unclear. METHODS: In this
      work, we investigated the alteration of methylation from placental tissues
      obtained from 152 normal infants or with NTDs in 130 children with neural-tube
      defects. Genome-wide changes in DNA methylation were measured using the NimbleGen
      microarray. The expression levels of 12 genes were also determined, and two genes
      (AKT2 and CDC25C) showed low expression in NTDs by quantitative real-time PCR
      analysis. Then, the methyhlated region of AKT2 promoter sequences were confirmed
      by massARRAY. RESULTS: A total of 150 differentially methylated regions (81 low
      methylated regions and 69 high methylated regions) were selected by microarray.
      The expression levels of AKT2 and CDC25C showed lower expression in NTDs. And the
      percentage of methyhlated region of AKT2 promoter were increased in NTDs.
      CONCLUSIONS: DNA mythelation was one of the possible epigenetic variations
      correlated with the occurrence of NTDs, and AKT2 may be a candidate gene for
      NTDs.

PMID- 27871478
TI  - Transendothelial migration of human umbilical mesenchymal stem cells across
      uterine endothelial monolayers: Junctional dynamics and putative mechanisms.
AB  - INTRODUCTION: During pregnancy, fetal stem cells can transfer to the maternal
      circulation and participate in tissue repair. How they transmigrate across
      maternal endothelial barriers and whether they can subsequently influence
      maternal endothelial integrity is not known. METHODS: Mesenchymal stem cells (WJ
      MSC) were isolated from Wharton's jelly and their interactions with human uterine
      microvascular endothelial cell (HUtMEC) monolayers, junctional occupancy and
      expression/phosphorylation of vascular endothelial (VE)- cadherin and vascular
      endothelial growth factor (VEGF-A) secretion was studied over 48h by real time,
      confocal microscopy, immunoblotting and ELISA. RESULTS: WJ-MSC displayed
      exploratory behaviour with interrogation of paracellular openings and spreading
      into the resultant increased gaps followed by closing of the endothelium over the
      WJ-MSC. 62% of added cells crossed within 22h to sub-endothelial niches. There
      was a concomitant loss of junctional VE-cadherin in HUtMEC followed by a full
      return and increased VE-cadherin expression after 22h. During early hours, VE
      cadherin showed a transient phosphorylation at Tyrosine (Tyr)-685 when VEGF-A
      secretion were high. From 16 to 22h, there was increased de-phosphorylation of
      Tyr-731. Anti-VEGF-A blocked Tyr-685 phosphorylation but not the decrease in P
      Tyr731; this partially inhibited WJ-MSC transmigration. DISCUSSION: Fetal WJ-MSC
      can traverse uterine endothelial monolayers by mediating a non-destructive
      paracellular pathway. They can promote junctional stability of uterine
      endothelium from the sub-endothelial niche. Mechanistically, WJ-MSC induces VEGF
      dependent phosphorylation events linked with paracellular permeability and VEGF
      independent de-phosphorylation events associated with leukocyte extravasation.
      Our data also allows consideration of a possible role of fetal MSC in mature
      functioning of the uterine vasculature needed for optimal utero-placental
      perfusion.

PMID- 27871479
TI  - Comparison of Matrigel and Matriderm as a carrier for human amnion-derived
      mesenchymal stem cells in wound healing.
AB  - Amnion-derived mesenchymal stem cells (AMSC) are a promising tool in regenerative
      medicine. Here we evaluated the utility of Matrigel and Matriderm as carrier for
      the topical application of AMSC to mice skin wounds. In both application forms,
      AMSC promoted neovascularization of the wound area. Matrigel proved as excellent
      matrix for AMSC and immigrating mouse cells, but the solid Matriderm enabled a
      more adequate positioning of AMSC into the wound. Although AMSC did not attach to
      Matriderm, they reliably induced wound reduction. Thus, a combined administration
      of AMSC/Matriderm could be beneficial to potentiate the encouraging effects on
      wound healing.

PMID- 27871480
TI  - Release of Growth Factors into Root Canal by Irrigations in Regenerative
      Endodontics.
AB  - INTRODUCTION: The aim of this study was to investigate the release of growth
      factors into root canal space after the irrigation procedure of regenerative
      endodontic procedure. METHODS: Sixty standardized root segments were prepared
      from extracted single-root teeth. Nail varnish was applied to all surfaces except
      the root canal surface. Root segments were irrigated with 1.5% NaOCl + 17% EDTA,
      2.5% NaOCl + 17% EDTA, 17% EDTA, or deionized water. The profile of growth
      factors that were released after irrigation was studied by growth factor array.
      Enzyme-linked immunosorbent assay was used to validate the release of
      transforming growth factor (TGF)-beta1 and basic fibroblast growth factor (bFGF)
      at 4 hours, 1 day, and 3 days after irrigation. The final concentrations were
      calculated on the basis of the root canal volume measured by cone-beam computed
      tomography. Dental pulp stem cell migration on growth factors released from root
      segments was measured by using Transwell assay. RESULTS: Total of 11 of 41 growth
      factors were detected by growth factors array. Enzyme-linked immunosorbent assay
      showed that TGF-beta1 was released in all irrigation groups. Compared with the
      group with 17% EDTA (6.92 +/- 4.49 ng/mL), the groups with 1.5% NaOCl + 17% EDTA
      and 2.5% NaOCl + 17% EDTA had significantly higher release of TGF-beta1 (69.04 +/
      30.41 ng/mL and 59.26 +/- 3.37 ng/mL, respectively), with a peak release at day
      1. The release of bFGF was detected at a low level in all groups (0 ng/mL to 0.43
      +/- 0.22 ng/mL). Migration assay showed the growth factors released from root
      segments induced dental pulp stem cell migration. CONCLUSIONS: The root segment
      model in present study simulated clinical scenario and indicated that the current
      irrigation protocol released a significant amount of TGF-beta1 but not bFGF. The
      growth factors released into root canal space induced dental pulp stem cell
      migration.

PMID- 27871481
TI  - Impacts of Contracted Endodontic Cavities on Instrumentation Efficacy and
      Biomechanical Responses in Maxillary Molars.
AB  - INTRODUCTION: Recently, we reported that in mandibular molars contracted
      endodontic cavities (CECs) improved fracture strength compared with traditional
      endodontic cavities (TECs) but compromised instrumentation efficacy in distal
      canals. This study assessed the impacts of CECs on instrumentation efficacy and
      axial strain responses in maxillary molars. METHODS: Eighteen extracted intact
      maxillary molars were imaged with micro-computed tomographic imaging (12-MUm
      voxel), assigned to CEC or TEC groups (n = 9/group), and accessed accordingly.
      Canals were instrumented (V-Taper2H; SSWhite Dental, Lakewood, NJ) with 2.5%
      sodium hypochlorite irrigation, reimaged, and the proportion of the modified
      canal wall determined. Cavities were restored with bonded composite resin (TPH
      Spectra-LV; Dentsply International, York, PA). Another 28 similar molars (n =
      14/group) with linear strain gauges (Showa Measuring Instruments, Tokyo, Japan)
      attached to mesiobuccal and palatal roots were subjected to load cycles (50-150
      N) in the Instron Universal Testing machine (Instron, Canton, MA), and the axial
      microstrain was recorded before access and after restoration. These 28 molars and
      additional 11 intact molars (control) were cyclically fatigued (1 million cycles,
      5-50 N, 15 Hz) and subsequently loaded to failure. Data were analyzed by the
      Wilcoxon rank sum and Kruskal-Wallis tests (alpha = 0.05). RESULTS: The overall
      mean proportion of the modified canal wall did not differ significantly between
      CECs (49.7% +/- 12.0%) and TECs (44.7% +/- 9.0%). Relative changes in axial
      microstrain responses to load varied in both groups. The mean load at failure for
      CECs (1703 +/- 558 N) did not differ significantly from TECs (1384 +/- 377 N) and
      was significantly lower (P < .005) for both groups compared with intact molars
      (2457 +/- 941 N). CONCLUSIONS: In maxillary molars tested in vitro, CECs did not
      impact instrumentation efficacy and biomechanical responses compared with TECs.

PMID- 27871482
TI  - Push-out Bond Strength of Fiber Posts to Intraradicular Dentin Using Multimode
      Adhesive System.
AB  - INTRODUCTION: Because there is little information about bond strength of fiber
      posts cemented with a universal adhesive system (UAS) with different resin
      cements, the aim of this study was to compare the effect of different bonding
      strategies in the application of UASs on push-out bond strength of fiber posts to
      intraradicular dentin. METHODS: Seventy-two single-rooted teeth were randomly
      divided into 6 groups: self-adhesive resin cement (SAC), dual-cure resin cement
      (DCC), UAS in the etch-and-rinse (E&R) mode and SAC (E&R + SAC), UAS in the self
      etch (SE) mode and SAC (SE + SAC), UAS in the E&R mode and DCC (E&R + DCC), and
      UAS in the SE mode and DCC (SE + DCC). The push-out test was conducted at a
      crosshead speed of 0.5 mm/min. Data were analyzed with 2-way analysis of variance
      (P < .05). RESULTS: Bond strength was significantly influenced by the adhesive
      strategies (P < .001). However, post space region did not have a significant
      effect on bond strength (P > .05). CONCLUSIONS: ClearfilSA Luting SAC (Kuraray
      Noritake Dental Inc, New York, NY) cannot be used alone for fiber post adhesion;
      it needs an adhesive. Universal adhesive in the SE mode is suggested. When UAS is
      used for luting fiber posts, the type of cement does not have any effect on bond
      strength.

PMID- 27871483
TI  - Vertical Load Induced with Twisted File Adaptive System during Canal Shaping.
AB  - INTRODUCTION: To evaluate the vertical load induced with the Twisted File
      Adaptive (TFA; SybronEndo, Orange, CA) system during canal shaping of extracted
      teeth by comparing it with the Twisted File (TF, SybronEndo), ProTaper Next (PTN;
      Dentsply Maillefer, Ballaigues, Switzerland), and ProTaper Universal (PTU,
      Dentsply Maillefer) systems. METHODS: Fifty-two root canals were shaped using the
      TFA, TF, PTN, or PTU systems (n = 13 for each system). They were shaped gently
      according to the manufacturers' instructions. During canal shaping, vertical
      loads were recorded and shown in 2 directions, apically and coronally directed
      loads. The vertical peak loads of 3 instrumentation stages were used for
      comparison. The effects of rotary systems on the mean positive and negative peak
      loads were analyzed statistically using the Kruskal-Wallis and Mann-Whitney tests
      at a confidence level of 95%. RESULTS: The overall pattern of the instantaneous
      loads appeared to increase with the use of successive instruments within the
      system. During canal shaping in all groups, the apically and coronally directed
      peak loads ranged from 0.84-7.55 N and 2.16-2.79 N, respectively. There were
      significant differences in both peak loads among the tested systems at each
      instrumentation stage. TFA had the lowest apically directed peak loads. In terms
      of coronally directed peak loads, the TFA and TF had a significantly lower amount
      of loads developed with their instruments than PTN and PTU. CONCLUSIONS: The
      choice of instrument system had an influence on the loads developed during canal
      shaping. TFA instruments were associated favorably with the lowest values of peak
      loads followed by TF, PTN, and PTU.

PMID- 27871484
TI  - Identification of a Nuclear Exosome Decay Pathway for Processed Transcripts.
AB  - The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei.
      Substrate targeting is facilitated by its co-factor Mtr4p/hMTR4, which links to
      RNA-binding protein adaptors. One example is the trimeric human nuclear exosome
      targeting (NEXT) complex, which is composed of hMTR4, the Zn-finger protein
      ZCCHC8, and the RNA-binding factor RBM7. NEXT primarily targets early and
      unprocessed transcripts, which demands a rationale for how the nuclear exosome
      recognizes processed RNAs. Here, we describe the poly(A) tail exosome targeting
      (PAXT) connection, which comprises the ZFC3H1 Zn-knuckle protein as a central
      link between hMTR4 and the nuclear poly(A)-binding protein PABPN1. Individual
      depletion of ZFC3H1 and PABPN1 results in the accumulation of common transcripts
      that are generally both longer and more extensively polyadenylated than NEXT
      substrates. Importantly, ZFC3H1/PABPN1 and ZCCHC8/RBM7 contact hMTR4 in a
      mutually exclusive manner, revealing that the exosome targets nuclear transcripts
      of different maturation status by substituting its hMTR4-associating adaptors.

PMID- 27871485
TI  - Unusual Processing Generates SPA LncRNAs that Sequester Multiple RNA Binding
      Proteins.
AB  - We identify a type of polycistronic transcript-derived long noncoding RNAs
      (lncRNAs) that are 5' small nucleolar RNA (snoRNA) capped and 3' polyadenylated
      (SPAs). SPA processing is associated with nascent mRNA 3' processing and kinetic
      competition between XRN2 trimming and Pol II elongation. Following
      cleavage/polyadenylation of its upstream gene, the downstream uncapped pre-SPA is
      trimmed by XRN2 until this exonuclease reaches the co-transcriptionally assembled
      snoRNP. This snoRNP complex prevents further degradation, generates a snoRNA 5'
      end, and allows continuous Pol II elongation. The imprinted 15q11-q13 encodes two
      SPAs that are deleted in Prader-Willi syndrome (PWS) patients. These lncRNAs form
      a nuclear accumulation that is enriched in RNA binding proteins (RBPs) including
      TDP43, RBFOX2, and hnRNP M. Generation of a human PWS cellular model by depleting
      these lncRNAs results in altered patterns of RBPs binding and alternative
      splicing. Together, these results expand the diversity of lncRNAs and provide
      additional insights into PWS pathogenesis.

PMID- 27871487
TI  - A joyful and glorious journey.

PMID- 27871486
TI  - Impact of MicroRNA Levels, Target-Site Complementarity, and Cooperativity on
      Competing Endogenous RNA-Regulated Gene Expression.
AB  - Expression changes of competing endogenous RNAs (ceRNAs) have been proposed to
      influence microRNA (miRNA) activity and thereby regulate other transcripts
      containing miRNA-binding sites. Here, we find that although miRNA levels define
      the extent of repression, they have little effect on the magnitude of the ceRNA
      expression change required to observe derepression. Canonical 6-nt sites, which
      typically mediate modest repression, can nonetheless compete for miRNA binding,
      with potency ~20% of that observed for canonical 8-nt sites. In aggregate, low
      affinity/background sites also contribute to competition. Sites with extensive
      additional complementarity can appear as more potent, but only because they
      induce miRNA degradation. Cooperative binding of proximal sites for the same or
      different miRNAs does increase potency. These results provide quantitative
      insights into the stoichiometric relationship between miRNAs and target
      abundance, target-site spacing, and affinity requirements for ceRNA-mediated gene
      regulation, and the unusual circumstances in which ceRNA-mediated gene regulation
      might be observed.

PMID- 27871488
TI  - Thoracic endovascular aneurysm repair for uncomplicated type B dissection.

PMID- 27871489
TI  - Invited commentary.

PMID- 27871490
TI  - Predictive models for mortality after ruptured aortic aneurysm repair do not
      predict futility and are not useful for clinical decision making.
AB  - OBJECTIVE: The clinical decision-making utility of scoring algorithms for
      predicting mortality after ruptured abdominal aortic aneurysms (rAAAs) remains
      unknown. We sought to determine the clinical utility of the algorithms compared
      with our clinical decision making and outcomes for management of rAAA during a 10
      year period. METHODS: Patients admitted with a diagnosis rAAA at a large
      university hospital were identified from 2005 to 2014. The Glasgow Aneurysm
      Score, Hardman Index, Vancouver Score, Edinburgh Ruptured Aneurysm Score,
      University of Washington Ruptured Aneurysm Score, Vascular Study Group of New
      England rAAA Risk Score, and the Artificial Neural Network Score were analyzed
      for accuracy in predicting mortality. Among patients quantified into the highest
      risk group (predicted mortality >80%-85%), we compared the predicted with the
      actual outcome to determine how well these scores predicted futility. RESULTS:
      The cohort comprised 64 patients. Of those, 24 (38%) underwent open repair, 36
      (56%) underwent endovascular repair, and 4 (6%) received only comfort care.
      Overall mortality was 30% (open repair, 26%; endovascular repair, 24%; no repair,
      100%). As assessed by the scoring systems, 5% to 35% of patients were categorized
      as high-mortality risk. Intersystem agreement was poor, with kappa values ranging
      from 0.06 to 0.79. Actual mortality was lower than the predicted mortality (50%
      70% vs 78%-100%) for all scoring systems, with each scoring system overestimating
      mortality by 10% to 50%. Mortality rates for patients not designated into the
      high-risk cohort were dramatically lower, ranging from 7% to 29%. Futility,
      defined as 100% mortality, was predicted in five of 63 patients with the Hardman
      Index and in two of 63 of the University of Washington score. Of these, surgery
      was not offered to one of five and one of two patients, respectively. If one of
      these two models were used to withhold operative intervention, the mortality of
      these patients would have been 100%. The actual mortality for these patients was
      60% and 50%, respectively. CONCLUSIONS: Clinical algorithms for predicting
      mortality after rAAA were not useful for predicting futility. Most patients with
      rAAA were not classified in the highest-risk group by the clinical decision
      models. Among patients identified as highest risk, predicted mortality was
      overestimated compared with actual mortality. The data from this study support
      the limited value to surgeons of the currently published algorithms.

PMID- 27871491
TI  - Invited commentary.

PMID- 27871492
TI  - The natural history of type II endoleaks after endovascular aneurysm repair for
      ruptured abdominal aortic aneurysm.
AB  - OBJECTIVE: The natural history of type II endoleak (T2EL) after endovascular
      aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA) remains
      elusive; as such, treatment guidelines are ill defined. The purpose of this study
      was to better delineate the natural history of T2EL after EVAR for rAAA in an
      effort to determine the need for reintervention and optimal surveillance.
      METHODS: A retrospective record review was conducted of all patients undergoing
      EVAR for rAAA in two large tertiary care academic vascular centers. Patient
      demographics, comorbidities, anatomic variables, and operative details were
      analyzed. Primary outcomes included the presence of T2EL, reintervention, delayed
      rupture, and aneurysm-related death. RESULTS: EVAR was used to treat rAAA in 56
      patients between 2000 and 2013. Mean follow-up of this cohort was 634 days.
      Completion arteriogram demonstrated T2ELs in 12 patients (21%), and an additional
      four T2ELs (7%) were found by postoperative computed tomography angiogram that
      were not identified on the completion angiogram. Body mass index was the only
      statistically significant variable associated with the development of T2EL (P =
      .03). Preoperative warfarin use, aortic thrombus burden, and device type did not
      correlate with T2EL development. Iliolumbar vessels supplied 75% (n = 12) of
      T2ELs. Of the 14 patients with T2ELs who underwent serial imaging
      postoperatively, six (43%) sealed spontaneously. Five patients (36%) underwent
      reintervention for T2EL by way of coil embolization-four in which treatment was
      initiated by attending preference. One patient was treated for ongoing anemia in
      the immediate postoperative period. There was no sac expansion, delayed rupture,
      or graft explantation. CONCLUSIONS: T2ELs after EVAR for rAAA are common and
      appear to be associated with a benign natural history if left untreated. Although
      many will spontaneously seal early in the postoperative period, those that remain
      patent do not appear to increase the risk for sac expansion or delayed rupture or
      affect patient survival. As such, a conservative approach to treatment of T2ELs
      in rAAA may be warranted.

PMID- 27871493
TI  - Diabetes does not worsen outcomes following infrageniculate bypass or
      endovascular intervention for patients with critical limb ischemia.
AB  - OBJECTIVE: Both open surgery and endovascular peripheral interventions have been
      shown to effectively improve outcomes in patients with peripheral arterial
      disease, but minimal data exist comparing outcomes performed at and below the
      knee among patients with diabetes (DM) specifically. The purpose of this study is
      to compare outcomes following open bypass (lower extremity bypass [LEB]) and
      peripheral vascular intervention (PVI) at and below the knee in patients with DM
      vs patients without DM (non-DM) with critical limb ischemia. METHODS: Data from
      the 2008-2014 Vascular Quality Initiative (VQI) were analyzed. All patients
      undergoing LEB or PVI at or below the knee for rest pain or tissue loss were
      included. One-year primary patency, major amputation, and mortality were compared
      for patients with DM vs patients without DM stratified by treatment approach.
      RESULTS: Overall, 2566 patients were included, including 500 patients (19%)
      undergoing LEB (DM = 355 vs non-DM = 145) and 2066 patients (81%) undergoing PVI
      (DM = 1463 vs non-DM = 603). Patients with DM were more frequently black (18% vs
      14%), had more comorbidities, and more frequently underwent revascularization for
      tissue loss (85% vs 58%) compared with patients without DM (all, P < .001).
      Within the LEB group, there were no significant differences in 1-year primary
      patency (74% vs 71%; P =.52), major amputation (16% vs 12%; P = .39), or
      mortality (10% vs 6%; P =.16) between DM vs non-DM patients. There were also no
      significant differences in 1-year primary patency (81% vs 79%; P = .36), major
      amputation (14% vs 11%; P =.09) or mortality (6% vs 7%; P =.30) among patients
      with DM vs patients without DM undergoing PVI. Multivariable analysis adjusting
      for baseline differences between groups demonstrated a nonsignificant trend
      toward better primary patency in the DM group following both LEB (hazard ratio,
      1.55; 95% confidence interval, 1.00-2.42; P = .05) and PVI (hazard ratio, 1.23;
      95% confidence interval, 0.97-1.56; P = .09). There were no significant
      differences in 1-year major amputation or mortality comparing patients with DM vs
      patients without DM for either LEB or PVI after risk adjustment (all, P >= .16).
      CONCLUSIONS: Critical limb ischemia resulting from arterial occlusive disease at
      or below the knee can be treated successfully with either open surgical bypass or
      endovascular interventions in both DM and non-DM patients. Aggressive attempts at
      limb salvage among patients with critical limb ischemia should be pursued
      regardless of DM status.

PMID- 27871495
TI  - Discussion.

PMID- 27871494
TI  - Current surgical management of carotid body tumors.
AB  - BACKGROUND: Carotid body tumors (CBTs) are rare. Management guidelines may
      include genetic testing for succinate dehydrogenase (SDH) mutations. We performed
      an institutional review of the surgical management of CBT. METHODS: A
      retrospective analysis (1994-2015) of CBT excisions at our institution was
      performed. Data obtained included demographics, genetic testing (if performed),
      intraoperative details, postoperative morbidity, and long-term outcomes. Data
      from the first CBT excision were included in patients with bilateral tumors.
      Genetic testing was routinely offered in patients with a family history of CBT or
      multiple paragangliomas. RESULTS: A total of 183 CBTs (124 female [67.7%]) were
      excised. A neck mass was present in 106 patients (57.9%), 24 patients (12.1%)
      presented with tenderness or neck pain, and 3 (1.6%) presented with cranial nerve
      dysfunction. Computed tomography (57.9%) or magnetic resonance imaging (51.3%)
      were the most commonly used imaging modalities. Preoperative angiography was
      performed in 73 patients (39.8%), and 62 of them (84.5%) underwent embolization
      or internal carotid balloon occlusion testing, or both. Mean tumor diameter was
      3.2 cm (range, 0.6-7.2 cm). There were 71 (38.8%), 75 (41%), and 37 (20.2%)
      Shamblin type 1, 2, and 3 tumors, respectively. Average operating time was 224
      minutes (range, 52-696 minutes). Average blood loss was 143.9 mL (range, 10-2000
      mL). Arterial reconstruction with an interposition graft was required in 10, and
      patch angioplasty was performed in four. Cranial nerve injury was permanent in 10
      (5.5%), and the rate of stroke was 1% (n = 2). A total of 382 lymph nodes were
      excised, and all were benign. There were no deaths <=30 days. Only one patient
      presented with malignant disease 2 years after CBT excision, and this patient did
      not undergo genetic testing. Thirty-four (18.6%) had a family history of CBT. SDH
      testing was performed in 18 patients, and 17 tested positive. Positive genetic
      testing had a correlation with earlier age at operation (P < .0001). Mean age at
      diagnosis of patients with SDH mutations was 38.0 years, and patients without
      known SDH mutations presented at a mean age of 50.3 years. In patients with SDH
      mutations, tumor diameter, operating time, blood loss, and distribution of
      Shamblin type 1, 2, and 3 lesions were not significantly different compared with
      the control group. CONCLUSIONS: CBT can be treated with minimal morbidity and
      mortality; however, the subgroup of patients with positive SDH mutations may
      represent a variant group of younger patients. Vascular surgeons should be aware
      of genetic testing to identify patients and family members who should undergo
      additional preoperative testing and monitoring for other paragangliomas.
      Concomitant lymph node dissection does not appear to add value in absence of
      clinic suspicion for malignancy.

PMID- 27871496
TI  - The presentation and management of aneurysms of the pancreaticoduodenal arcade.
AB  - OBJECTIVE: Gastroduodenal artery aneurysms (GDAAs) and pancreaticoduodenal artery
      aneurysms (PDAAs) are uncommon lesions associated, however, with a significant
      risk of rupture. This study describes the clinical presentation, associated
      imaging findings, and operative strategies for these aneurysms. METHODS: The
      records of all patients with GDAAs or PDAAs identified through an institutional
      database by axial imaging between 1994 and 2014 were retrospectively reviewed.
      Data on presenting symptoms, comorbid conditions, imaging findings, and outcomes
      after operative intervention were collected and examined. RESULTS: We identified
      11 GDAAs and 25 PDAAs in 35 patients. Mean size of the GDAAs was 31.1 mm (range,
      10-60 mm) and mean size of the PDAAs was 19.1 mm (range, 10-48 mm). At
      presentation, 13 aneurysms (36%) were symptomatic and seven aneurysms (19.4%)
      were ruptured. Median size of ruptured aneurysms was 20 mm (range, 10-60 mm). On
      axial imaging, 24 aneurysms (67%) were associated with a severe stenosis or
      occlusion of the celiac axis origin, and 11 aneurysms (31%) were thought to be
      associated with compression of the celiac axis in the setting of median arcuate
      ligament syndrome. Twenty-four aneurysms (67%) underwent repair. Of these
      aneurysms, 18 (75%) were successfully managed with primary endovascular repair
      (coil embolization with or without celiac stent), whereas endovascular therapy
      failed in two (8%) and required open repair. Four aneurysms (17%) were treated
      with primary open repair. Overall 30-day morbidity and mortality after aneurysm
      repair were 29% and 4%, respectively. CONCLUSIONS: GDAAs and PDAAs are uncommon
      lesions that are often associated with a celiac axis stenosis/occlusion leading
      to altered hemodynamics in the pancreaticoduodenal arcade. These aneurysms are
      prone to rupture regardless of size, and intervention is accordingly recommended
      for all aneurysms upon recognition. Despite the concordant celiac axis
      obstruction and concern for maintenance of hepatic circulation, endovascular
      repair of these aneurysms is generally successful and should be considered as the
      initial operative approach.

PMID- 27871497
TI  - Possible consequences of regionally based bundled payments for diabetic
      amputations for safety net hospitals in Texas.
AB  - OBJECTIVE: Ongoing health reform in the United States encourages quality-based
      reimbursement methods such as bundled payments for surgery. The effect of such
      changes on high-risk procedures is unknown, especially at safety net hospitals.
      This study quantified the burden of diabetes-related amputation and the potential
      financial effect of bundled payments at safety net hospitals in Texas. METHODS:
      We performed a cross-sectional analysis of diabetic amputation burden and charges
      using publically available data from Centers for Medicare and Medicaid and the
      Texas Department of Health from 2008 to 2012. Using hospital referral region
      (HRR)-level analysis, we categorized the proportion of safety net hospitals
      within each region as very low (0%-9%), low (10%-20%), average (20%-33%), and
      high (>33%) and compared amputation rates across regions using nonparametric
      tests of trend. We then used charge data to create reimbursement rates based on
      HRR to estimate financial losses. RESULTS: We identified 51 adult hospitals as
      safety nets in Texas. Regions varied in the proportion of safety net hospitals
      from 0% in Victoria to 65% in Harlingen. Among beneficiaries aged >65, amputation
      rates correlated to the proportion of safety net hospitals in each region; for
      example, patients in the lowest quartile of safety net had a yearly rate of 300
      amputations per 100,000 beneficiaries, whereas those in the highest quartile had
      a yearly rate of 472 per 100,000 (P = .007). Charges for diabetic amputation
      related admissions varied almost 200-fold, from $5000 to $1.4 million. Using
      reimbursement based on HRR to estimate a bundled payment, we noted net losses
      would be higher at safety net vs nonsafety net hospitals ($180 million vs $163
      million), representing a per-hospital loss of $1.6 million at safety nets vs
      $700,000 at nonsafety nets (P < .001). CONCLUSIONS: Regions with a high
      proportion of safety net hospitals perform almost half of the diabetic
      amputations in Texas. Changes to traditional payment models should account for
      the disproportionate burden of high-risk procedures performed by these hospitals.

PMID- 27871498
TI  - Invited commentary.

PMID- 27871499
TI  - Invited commentary.

PMID- 27871500
TI  - Intrathoracic origin of the left renal artery.

PMID- 27871501
TI  - Late discovery of a rare anomaly of the right aortic arch and an isolated left
      subclavian artery.

PMID- 27871502
TI  - Screening for abdominal aortic aneurysm in asymptomatic adults.
AB  - BACKGROUND: This report was produced for the Canadian Task Force on Preventive
      Health Care to provide guidelines on screening for abdominal aortic aneurysm
      (AAA) with ultrasound scan. PURPOSE: The aim of this systematic review is to
      examine the evidence on benefits and harms of AAA screening. SEARCH STRATEGY:
      This systematic review considered studies from the most recent United States
      Preventive Services Task Force review on AAA screening and passed through the
      screening process with citations identified in our search up to April 2015
      (PROSPERO Registration #CRD42015019047). RESULTS: For benefits of one-time AAA
      screening in men compared with controls, pooled analyses from four randomized
      controlled trials with moderate quality evidence showed significant reductions in
      AAA-related mortality and AAA rupture rate up to 13 to 15 years of follow-up with
      42% reduction (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.39-0.88;
      number needed to screen = 212) and 38% reduction (RR, 0.62; 95% CI, 0.45-0.86;
      number needed to screen = 200), respectively. The effect of on all-cause
      mortality was marginally significant for longer follow-up. The Chichester trial
      examined the benefits of one-time AAA screening in women and found no significant
      differences between screening and control arms for up to 10 years of follow-up
      (RR, 0.88; 95% CI, 0.72-1.07). For consequences of one-time AAA screening in men
      compared with controls, there was a significant increase in the total number of
      AAA-related procedures over a follow-up of 13 to 15 years (2.16 times more
      likely) compared with controls. For harms of one-time AAA screening, no
      significant differences were observed in 30-day postoperative mortality for
      elective and emergency operations with compared control groups. Evidence from the
      Multicenter Aneurysm Screening Study trial using 13-year follow-up data showed
      that one-time AAA screening with ultrasound scan was potentially associated with
      an overdiagnosis of 45% (95% CI, 42%-47%) among screen-detected men. CONCLUSIONS:
      Population-based screening for AAA with ultrasound scan in asymptomatic men aged
      65 years and older showed statistically significant reductions in AAA-related
      mortality and rupture and, hence, avoids unnecessary AAA-related deaths. The
      current evidence showed no benefit of one-time AAA screening in woman. Limited
      evidence is available on the benefits of repeat AAA screening and targeted
      screening approaches based on risk factors for AAA. Future research should
      explore the differential benefits of AAA screening based on risk factors that
      increase risk for developing AAA.

PMID- 27871503
TI  - Statin use in patients with peripheral arterial disease.
AB  - BACKGROUND: Statins are recommended for use in patients with peripheral arterial
      disease (PAD) to reduce cardiovascular events and mortality. However, much of the
      data regarding benefits of statins stem from the cardiovascular literature. Here,
      we review the literature regarding statin use specifically in patients with PAD
      regarding its effects on cardiovascular events and mortality, limb-related
      outcomes, statin use after endovascular interventions, statin dosing, and
      concerns about statins. METHODS: We performed a literature review using PubMed
      for literature after the year 2000. Search terms included "statins," "peripheral
      arterial disease," "peripheral vascular disease," "lipid-lowering medication,"
      and "cardiovascular disease." RESULTS: There is good evidence of statins lowering
      cardiovascular events and cardiovascular-related mortality in patients with PAD.
      Though revascularization rates were reduced with statins, amputation rates and
      amputation-free survival did not improve. Small randomized controlled trials show
      that patients taking statins can slightly improve pain-free walking distance or
      pain-free walking time, although the extent of the effect on quality of life is
      unclear. Statin use for patients undergoing endovascular interventions is
      recommended because of the reduction of postoperative cardiovascular events. Not
      enough data exist to support local effects of systemic statin therapy, such as
      prevention of restenosis. For statin dosing, there is little increased benefit to
      intense therapy compared with the adverse effects, whereas moderate-dose therapy
      has significant benefits with very few adverse effects. Adverse effects of
      moderate-dose statin therapy are rare and mild and are greatly outweighed by the
      cardiovascular benefits. CONCLUSIONS: There is strong evidence to support use of
      statins in patients with PAD to reduce cardiovascular events and mortality. Use
      in patients undergoing open and endovascular interventions is also recommended.
      Statin use may reduce the need for revascularization, but reductions in
      amputation have not been shown. Moderate-dose statin therapy is safe, and the
      minor risks are greatly outweighed by benefits.

PMID- 27871504
TI  - Efficacy and safety of sugammadex compared to neostigmine for reversal of
      neuromuscular blockade: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND AND OBJECTIVE: Sugammadex has been introduced for reversal of
      rocuronium (or vecuronium)-induced neuromuscular blockade (NMB). Although its
      efficacy has been established, data are conflicting whether it is safer than
      neostigmine traditionally used for reversing NMB. DESIGN: Meta-analysis of data
      about effectiveness and safety of sugammadex compared to neostigmine for
      reversing NMB in adults was performed using the PRISMA methodology. SETTING:
      University medical hospital. METHODS: A comprehensive search was conducted using
      PubMed, Web of Science, and Cochrane Library electronic databases to identify
      English-language randomized controlled trials. Two reviewers independently
      selected the trials; extracted data on reversal times, incomplete reversals of
      NMB, and adverse events (AEs); and assessed the trials' methodological quality
      and evidence level. Only AEs that were related to study drug by a blinded safety
      assessor were considered for meta-analysis. PATIENTS: A total of 1384 patients
      from 13 articles were included in this meta-analysis. MAIN RESULTS: Compared to
      neostigmine, sugammadex was faster in reversing NMB (P<.0001) and more likely to
      be associated with higher train-of-four ratio values at extubation (mean
      difference, 0.18; 95% confidence interval [CI], 0.14-0.22; P<.0001) and lower
      risk of postoperative residual curarization after extubation (odds ratio [OR],
      0.05; 95% CI, 0.01-0.43; P=.0068). Compared to neostigmine, sugammadex was
      associated with a significantly lower likelihood of global AEs (OR, 0.47; 95% CI,
      0.34-0.66; P<.0001), respiratory AEs (OR, 0.36; 95% CI, 0.14-0.95; P=.0386),
      cardiovascular AEs (OR, 0.23; 95% CI, 0.08-0.61; P=.0036), and postoperative
      weakness (OR, 0.45; 95% CI, 0.21-0.97; P=.0409). Sugammadex and neostigmine were
      associated with a similar likelihood of postoperative nausea and vomiting (OR,
      1.23; 95% CI, 0.70-2.15; P=.4719), pain (OR, 1.06; 95% CI, 0.15-7.36; P=.9559),
      neurologic AEs (OR, 1.47; 95% CI, 0.52-4.17; P=.4699), general AEs (OR, 0.75; 95%
      CI, 0.47-1.21; P=.2448), and changes in laboratory tests' values (OR, 0.57; 95%
      CI, 0.18-1.78; P=.3368). CONCLUSIONS: Results from this meta-analysis suggest
      that sugammadex is superior to neostigmine, as it reverses NMB faster and more
      reliably, with a lower risk of AEs.

PMID- 27871505
TI  - Operating room discharge after deep neuromuscular block reversed with sugammadex
      compared with shallow block reversed with neostigmine: a randomized controlled
      trial.
AB  - OBJECTIVE: To determine if reversing a deep or moderate block with sugammadex,
      compared with a shallow block reversed with neostigmine, reduces the time to
      operating room discharge after surgery and the time spent in the postanesthesia
      care unit. DESIGN: A randomized controlled trial. SETTING: Monocentric study
      performed from February 2011 until May 2012. PATIENTS: One hundred consenting
      women with American Society of Anesthesiologists grade I or II were randomized
      into 2 groups. INTERVENTION: Laparoscopic hysterectomy was performed under
      desflurane general anesthesia. For the neostigmine (N) group, 0.45 mg . kg-1
      rocuronium was followed by spontaneous recovery. A 5-mg rescue bolus was
      administered only if surgical evaluation was unacceptable. At the end of surgery,
      50 MUg . kg-1 neostigmine with glycopyrrolate was administered. For the
      sugammadex (S) group, a higher intubating rocuronium dose (0.6 mg . kg-1) was
      followed by 5-mg boluses each time the train-of-four count exceeded 2. Sugammadex
      (2-4 mg . kg-1) was administered to reverse the block. All patients were
      extubated after obtaining a train-of-four ratio of 0.9. MEASUREMENTS: The
      duration between the end of surgery and operating room discharge and the time
      spent in the postanesthesia care unit. MAIN RESULTS: The time till operating room
      discharge was shorter and more predictable in group S (9.15+/-4.28 minutes vs
      13.87+/-11.43 minutes in group N; P=.005). The maximal duration in group S was 22
      minutes, compared with 72 minutes in group N. The time spent in the
      postanesthesia care unit was not significantly different (group S: 47.75+/-31.77
      minutes and group N: 53.43+/-40.57 minutes; P=.543). CONCLUSION: Maintaining a
      deep neuromuscular block during laparoscopic hysterectomy reversed at the end of
      the procedure with sugammadex enabled a faster and more predictable time till
      operating room discharge than did the classical combination of a shallower block
      reversed with neostigmine.

PMID- 27871506
TI  - Elective cholecystectomy performed on patient with variegate porphyria-Propofol
      based total intravenous anesthesia with target-controlled infusion.
AB  - Porphyria is caused by disorders of enzymes that synthetize porphyrins. Both
      elective and emergency surgical procedures on patient suffering from porphyria
      may provoke acute symptoms. These patients require special anesthetic management
      since some of commonly used anesthetic agents may also induce acute manifestation
      of porphyria. We present the case of 53-year-old woman previously diagnosed with
      porphyria who underwent elective laparoscopic cholecystectomy. Propofol-based
      total intravenous anesthesia with target-controlled infusion was used. Such
      conduct proved to be safe regarding clinical symptoms, although biochemical
      markers were slightly elevated after procedure. Propofol seems to be the safest
      hypnotic drug to use in porphyria; however, special care should be taken is such
      cases.

PMID- 27871507
TI  - Use of GABAergic sedatives after subarachnoid hemorrhage is associated with worse
      outcome-preliminary findings.
AB  - STUDY OBJECTIVE: Recent experimental evidence identified GABAergic sedation as a
      possible cause for deprived neuroregeneration and poor outcome after acute brain
      injury. Patients with aneurysmal subarachnoid hemorrhage are often sedated, and
      GABAergic sedation, such as midazolam and propofol, is commonly used. DESIGN:
      Retrospective cohort study based on a prospectively established database.
      SETTING: Single-center neurointensive care unit. PATIENTS: Twenty-nine patients
      after subarachnoid hemorrhage. INTERVENTION: Noninterventional study.
      MEASUREMENTS: The relationship between mean GABAergic sedative dose during the
      acute phase and outcome after 6 months according to the Glasgow Outcome Scale,
      and initial Glasgow Coma Scale was investigated. MAIN RESULTS: Use of GABAergic
      sedatives was negatively correlated with Glasgow Outcome Scale (r2=0.267;
      P=.008). Administration of sedatives was independent of the initial Glasgow Coma
      Scale. GABAergic sedatives flunitrazepam, midazolam, and propofol were used
      differently during the first 10 days after ictus. CONCLUSION: Administration of
      GABAergic sedation was associated with an unfavorable outcome after 6 months. To
      avoid bias (mainly through the indication to use sedation), additional
      experimental and comparative clinical investigation of, for example, non
      GABAergic sedation, and clinical protocols of no sedation is necessary.

PMID- 27871508
TI  - Perineural catheter infection: a systematic review of the literature.
AB  - Perineural catheter infection is a rare but potentially dramatic complication of
      continuous peripheral nerve block. Different risk factors have been identified
      and the incidence of infection is increased in trauma victims, intensive care
      unit patients, immunodeficient individuals, and diabetic patients. Also,
      postoperative hyperglycemia, the absence of antibiotic prophylaxis, and catheter
      lasting more than 48 hours seem to be associated with a greater risk of
      infection. Skin disinfection and a strict aseptic technique during catheter
      placement are fundamental. The use of micropore filters, antiseptic dressings,
      catheter tunneling, and aseptic preparation of the infused drug has all been
      hypothesized to reduce infection rate, but the existing evidence is conflicting.
      Infection is a rare complication of continuous peripheral nerve blocks. Severe
      and even fatal cases have been reported, even if morbidity is generally very low.
      The identification of high risk patients and adoption of preventive measures
      might reduce the incidence of this complication.

PMID- 27871509
TI  - A cross-sectional study of preoperative medication adherence and early
      postoperative recovery.
AB  - STUDY OBJECTIVE: To quantify the impact of preoperative medication adherence on
      recovery length of stays and complication rates. DESIGN: Cross-sectional
      analytical study. SETTING: Postanesthetic care unit (PACU) of a single-center
      tertiary hospital. PATIENTS: Surgical patients admitted for surgery at our
      institution over a 4-month period. INTERVENTION: A data collection tool was used
      to collect demographic data, length of stay in recovery, prespecified conditions
      likely to impact on PACU recovery (chronic pain, insulin-dependent diabetes,
      epilepsy, hypertension, on a methadone program, and Parkinson disease),
      medication compliance, and complications in PACU. MEASUREMENTS: Differences among
      categorical variables were assessed for significance using the chi2 test;
      continuous parametric data were compared using a time to survival analysis via
      Kaplan-Meier estimates and Cox proportional hazard regressions to account for
      possible confounders. MAIN RESULTS: Preoperative medication compliance for the
      prespecified conditions was 65.1%. Patients with a preoperative condition spent
      more time in the PACU compared to patients without a preoperative condition. Time
      in PACU was not significantly longer for patients who took their medications
      compared to those who failed to take their medications. Patients with multiple
      prespecified conditions were more likely to incur a postoperative complication
      compared to patients without a prespecified condition. Patients with preoperative
      hypertension and insulin-dependent diabetes incurred higher complication rates in
      PACU for medication nonadherence compared to medication adherence. CONCLUSION:
      This study taken together with accruing evidence suggests that preoperative
      medication omission remains an ongoing issue that can influence complication
      rates in the PACU. Patients with preoperative conditions stay longer in PACU, and
      medication omission was associated with higher rates of certain postoperative
      complications in PACU. This identifies patients likely to require more
      interventions and greater recovery resources. Further research into the impact of
      medication omission on recovery parameters after discharge from the PACU is
      warranted.

PMID- 27871510
TI  - Anticholinergic premedication to prevent bradycardia in combined spinal
      anesthesia and dexmedetomidine sedation: a randomized, double-blind, placebo
      controlled study.
AB  - OBJECTIVE: When dexmedetomidine is used in patients undergoing spinal anesthesia,
      high incidence of bradycardia in response to parasympathetic activation is
      reported. Therefore, we aimed to evaluate the effectiveness of atropine
      premedication for preventing the incidence of bradycardia and the hemodynamic
      effect on patients undergoing spinal anesthesia with sedation by dexmedetomidine.
      DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Operating
      room. PATIENTS: One hundred fourteen patients (age range, 2-65 years; American
      Society of Anesthesiology class I-II) participated in this study, willing to be
      sedated and to undergo spinal anesthesia. INTERVENTION: The patients were divided
      into 2 groups: group A and group C. After performing spinal anesthesia,
      dexmedetomidine was infused at a loading dose of 0.6 MUg/kg for 10 minutes,
      followed by an infusion at 0.25 MUg/(kg h). Simultaneously with the loading dose
      of dexmedetomidine, patients in group A received an intravenous bolus of 0.5 mg
      atropine, whereas patients in group C received an intravenous normal saline
      bolus. MEASUREMENT: Data on administration of atropine and ephedrine were
      collected. Hemodynamic data including heart rate, systolic blood pressure,
      diastolic blood pressure (DBP), and mean blood pressure (MBP) were also recorded.
      MAIN RESULTS: The incidence of bradycardia requiring atropine treatment was
      significantly higher in group C than group A (P=.035). However, the incidence of
      hypotension needing ephedrine treatment showed no significant difference between
      the 2 groups (P=.7). Systolic blood pressure and heart rate showed no significant
      differences between the 2 groups (P=.138 and .464, respectively). However, group
      A showed significant increases in DBP and MBP, and group C did not (P=.014 and
      .008, respectively). CONCLUSION: Prophylactic atropine reduces the incidence of
      bradycardia in patients undergoing spinal anesthesia with dexmedetomidine
      sedation. However, DBP and MBP showed significant increases in patients when
      prophylactic atropine was administrated. Therefore, atropine premedication should
      be administered cautiously.

PMID- 27871511
TI  - Zika virus: review and obstetric anesthetic clinical considerations.
AB  - STUDY OBJECTIVES: To review the clinical and basic science literature regarding
      Zika viral illness and highlight relevant findings for obstetric
      anesthesiologists. This review provides a global review of Zika viral illness,
      transmission patterns, pathophysiology of disease, and anesthetic management of
      the parturient with Zika viral illness and associated comorbidities. DESIGN:
      Systematic review. SETTING: Large academic hospital. SUBJECTS: None.
      INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: None. CONCLUSION: With the
      rapid spread of Zika virus and expected increase of spread in the summer of 2016,
      this review provides anesthesiologists with current recommendations, physiologic
      alterations, and anesthetic considerations in regard to the parturient with Zika
      viral illness and associated diseases.

PMID- 27871512
TI  - Case report: management of differential diagnosis and treatment of severe
      anaphylaxis in the setting of spinal anesthesia.
AB  - The purpose of this case report is to educate fellow anesthesiologists of a
      complicated differential diagnosis for sudden cardiovascular collapse after
      spinal anesthesia. We report a case where anaphylaxis occurred while under spinal
      anesthesia and resulted in difficult resuscitation. A 58-year-old woman
      undergoing bilateral knee replacements under spinal anesthesia experienced sudden
      seizure and cardiovascular collapse from acute anaphylactic shock while
      administering a cephalosporin. Local anesthetic toxicity, high spinal, and
      anaphylaxis were considered due to overlapping of symptoms. Successful
      resuscitation required prolonged advanced cardiac life support with substantially
      larger doses of epinephrine. Anaphylactic shock under spinal anesthesia is an
      acute and life-threatening complication, worsened by the spinal-induced
      sympathectomy, and aggressive resuscitation is warranted. Despite the presence of
      overlapping symptoms of differential diagnoses, rapid identification of the cause
      of cardiovascular collapse is crucial given that resuscitation treatment
      modalities may conflict. Timing of antibiotic administration should be adjusted
      for spinal anesthesia cases to allow time to detect possible anaphylaxis.

PMID- 27871513
TI  - Disagreement between fourth generation FloTrac and LiDCOrapid measurements of
      cardiac output and stroke volume variation during laparoscopic colectomy.
AB  - STUDY OBJECTIVE: To determine the agreement between cardiac output (CO) and
      stroke volume variation (SVV) measured simultaneously by the fourth generation
      FloTrac/Vigileo system and LiDCOrapid system during pneumoperitoneum in patients
      undergoing laparoscopic colectomy. DESIGN: Retrospective observational study.
      SETTINGS: Operating room in a general hospital. PATIENTS: Ten patients (American
      Society of Anesthesiologist 1 or 2) without preoperative anemia. INTERVENTIONS: A
      22-gauge catheter was inserted in the radial artery after induction of
      anesthesia. The arterial line was split to monitor CO and SVV simultaneously with
      the LiDCOrapid and fourth generation FloTrac/Vigileo systems. All data were
      downloaded from each system after surgery and simultaneous paired COFloTrac,
      COLiDCO and SVVFloTrac, SVVLiDCO values estimated every 1 minute during the
      pneumoperitoneum were analyzed. MEASUREMENTS: To assess the agreement after
      carbon dioxide insufflation, a scatter 4-quadrant plot was generated using paired
      DeltaCO values (changes in COFloTrac and COLiDCO just before pneumoperitoneum and
      3 minutes after the induction of pneumoperitoneum). For data in which SVVFloTrac
      was >9% but <16% and cardiac index measured by FloTrac/Vigileo was <2.5 L/min per
      m2 during stable pneumoperitoneum (the period from 5 minutes after Trendelenburg
      position until discontinuation of pneumoperitoneum), simultaneously measured
      paired SVVFloTrac and SVVLiDCO were plotted every 1 minute using the Bland-Altman
      method. MAIN RESULTS: A concordance ratio for changes in CO after the induction
      of pneumoperitoneum was 83% in 4-quadrant plot. During stable pneumoperitoneum,
      702 paired SVVFloTrac and SVVLiDCO matched the criteria. These data sets were
      plotted by the Bland-Altman method and the bias and 95% limit of agreement of SVV
      were 2.01 and -2.63% to 6.65%, respectively, with 38% percentage error. The
      regression equation was SVVLiDCO = 0.98 * SVVFloTrac- 1.73 with Pearson
      correlation coefficient of 0.55. CONCLUSIONS: Our study showed disagreement
      between the 2 methods and the hemodynamic parameters measured by one of the two
      devices should be interpreted with caution before therapeutic interventions.

PMID- 27871514
TI  - Cost impact of unexpected disposition after orthopedic ambulatory surgery
      associated with category of anesthesia provider.
AB  - STUDY OBJECTIVE: To provide estimates of the costs and health outcomes
      implications of the excess risk of unexpected disposition for nurse anesthetist
      (NA) procedures. DESIGN: A projection model was used to apply estimates of costs
      and health outcomes associated with the excess risk of unexpected disposition for
      NAs reported in a recent study. SETTING: Ambulatory and inpatient surgery.
      PATIENTS: Base-case model parameters were based on estimates taken from peer
      reviewed publications when available, or from other sources including data for
      all hospital stays in the United States in 2013 from the Healthcare Cost and
      Utilization Project Web site. The impact of parameter uncertainty was assessed
      using 1-way and 2-way sensitivity analyses. INTERVENTIONS: Not applicable.
      MEASUREMENTS: Major complication rates, relative risks of complications,
      anesthesia costs, costs of complications, and cost-effectiveness ratios. MAIN
      RESULTS: In the base-case model, there were on average 2.3 fewer unexpected
      dispositions for physician anesthesiologists compared with NAs. Overall,
      anesthesia-related costs (including the cost of managing unexpected dispositions)
      were estimated to be about $31 higher per procedure for physician
      anesthesiologists compared with NAs. Alternative model scenarios in the
      sensitivity analysis produced estimates of smaller additional costs associated
      with physician anesthesia administration, to the point of cost savings in some
      scenarios. CONCLUSIONS: Provision of anesthesia for ambulatory knee and shoulder
      procedures by physician anesthesiologists results in better health outcomes, at a
      reasonable additional cost, compared with procedures with NA-administered
      anesthesia, at least when using updated cost-effectiveness willingness-to-pay
      benchmarks.

PMID- 27871516
TI  - Pediatric patients on ketogenic diet undergoing general anesthesia-a medical
      record review.
AB  - STUDY OBJECTIVE: To identify guidelines for anesthesia management and determine
      whether general anesthesia is safe for pediatric patients on ketogenic diet (KD).
      DESIGN: Retrospective medical record review. SETTING: Postoperative recovery
      area. PATIENTS: All pediatric patients who underwent general anesthesia while on
      KD between 2009 and 2014 were reviewed. We identified 24 patients who underwent a
      total of 33 procedures. All children were on KD due to intractable epilepsy. The
      age of patients ranged from 1 to 15 years. INTERVENTION: General anesthesia for
      the scheduled procedures. MEASUREMENTS: Patients' demographics, seizure history,
      type of procedure; perioperative blood chemistry, medications including the
      anesthesia administered, and postoperative complications. MAIN RESULTS: Twenty
      four patients underwent a total of 33 procedures. The duration of KD treatment at
      the time of general anesthesia ranged from 4 days to 8 years. Among the 33
      procedures, 3 patients had complications that could be attributable to KD and
      general anesthesia. A 9-year-old patient experienced increased seizures on
      postoperative day 0. An 8-year-old patient with hydropcephalus developed
      metabolic acidosis on postoperative day 1, and a 7-year-old patient's procedure
      was complicated by respiratory distress and increased seizure activity in the
      postanesthesia care unit. CONCLUSION: This study showed that it is relatively
      safe for children on KD to undergo general anesthesia. The 3 complications
      attributable to general anesthesia were mild, and the increased seizure
      frequencies in 2 patients returned back to baseline in 24 hours. Although normal
      saline is considered more beneficial than lactated Ringer's solution in patients
      on KD, normal saline should also be administered carefully because of the risk of
      exacerbating patients' metabolic acidosis. One should be aware of the potential
      change of the ketogenic status due to drugs given intraoperatively.

PMID- 27871515
TI  - Perioperative antiplatelet therapy and cardiovascular outcomes in patients
      undergoing joint and spine surgery.
AB  - STUDY OBJECTIVE: Perioperative thrombotic complications after orthopedic surgery
      are associated with significant morbidity and mortality. The use of aspirin to
      reduce perioperative cardiovascular complications in certain high-risk cohorts
      remains controversial. Few studies have addressed aspirin use, bleeding, and
      cardiovascular outcomes among high-risk patients undergoing joint and spine
      surgery. DESIGN/SETTING/PATIENTS: We performed a retrospective comparison of
      adults undergoing knee, hip, or spine surgery at a tertiary care center during 2
      periods between November 2008 and December 2009 (reference period) and between
      April 2013 and December 2013 (contemporary period). MEASUREMENTS: Patient
      demographics, comorbidities, management, and outcomes were ascertained using
      hospital datasets. MAIN RESULTS: A total of 5690 participants underwent 3075
      joint and spine surgeries in the reference period and 2791 surgeries in the
      contemporary period. Mean age was 61+/-13 years, and 59% were female. In the
      overall population, incidence of myocardial injury (3.1% vs 5.8%, P<.0001),
      hemorrhage (0.2% vs 0.8%, P=.0009), and red blood cell transfusion (17.2% vs
      24.8%, P<.001) were lower in the contemporary period. Among 614 participants with
      a preoperative diagnosis of coronary artery disease (CAD), in-hospital aspirin
      use was significantly higher in the contemporary period (66% vs 30.7%, P<.0001);
      numerically, fewer participants developed myocardial injury (13.5% vs 19.3%,
      P=.05), had hemorrhage (0.3% vs 2.1%, P=.0009), and had red blood cell
      transfusion (37.2% vs 44.2%, P<.001) in the contemporary vs reference period.
      CONCLUSIONS: In a large tertiary care center, the incidence of perioperative
      bleeding and cardiovascular events decreased over time. In participants with CAD,
      perioperative aspirin use increased and appears to be safe.

PMID- 27871517
TI  - Guidelines for preoperative investigations for elective surgery at Queen
      Elizabeth Hospital: effects on practices, outcomes, and costs.
AB  - STUDY OBJECTIVE: We endeavor to assess the impact of introduction of guidelines
      for preoperative investigations (PIs) on anesthetic practices and costs and
      compare their efficacy to current practices. DESIGN: A prospective study.
      SETTING: Queen Elizabeth Hospital, Barbados. PATIENTS: Participants comprised all
      patients undergoing general, epidural, spinal, and regional anesthesia, with the
      exception of emergency cases or instances where an anesthesiologist was not
      required. INTERVENTION: Introduction of formal guidelines for preoperative
      investigations. MEASUREMENTS: The patterns of preoperative testing were assessed
      by audit, and this assessment was repeated postintervention. PI guidelines
      developed were presented to all surgical departments. MAIN RESULTS: For younger
      patients (<60 years), the mean number of tests decreased from 3.42+/-1.8 in the
      preguideline group to 2.89+/-1.98 in the postguideline group (P=.042). The total
      number of chest x-rays decreased by 14.8% (P=.012) and full blood counts by 7.6%
      (P=.036). The implementation of PI guidelines led to overall savings of US $7589
      per 1000 patients, which is equivalent to (US $40,745.50 per annum). The most
      notable savings were due to decreased number of chest x-rays. PIs were performed
      routinely even in the absence of clinical indications. CONCLUSION: Our findings
      indicate that introduction of guidelines has reduced the level of preanesthetic
      investigations to some extent; nevertheless, further change is desirable. In
      addition, costs to the institution were decreased with no compromise to patient
      safety.

PMID- 27871518
TI  - Continuous ambulatory adductor canal catheters for patients undergoing knee
      arthroplasty surgery.
AB  - STUDY OBJECTIVE: To determine after knee arthroplasty surgery the feasibility of
      discharging patients home on postoperative day 1 with continuous adductor canal
      blocks. DESIGN: Retrospective case series. SETTING: Outpatient setting after
      hospital discharge. PATIENTS: Patients undergoing knee arthroplasty surgery from
      October 2013 to August 2014. INTERVENTIONS: All patients received continuous
      adductor canal catheters for postoperative analgesia and were discharged to home
      on postoperative day 1. Continuous catheters were intended to remain intact in
      the ambulatory setting through postoperative day 3. MEASUREMENTS: Data obtained
      included demographic information, duration of hospital stay, resting and active
      pain scores, opioid utilization, opioid-induced adverse effects, complications
      relating to the perineural catheter, and hospital readmissions. MAIN RESULTS:
      Sixty-nine of 582 patients (11.9%) were discharged to home on postoperative day
      1. The median numerical pain score after discharge with a continuous adductor
      canal block was <=2 at rest and <=4 with activity. After block discontinuation on
      postoperative day 4, median pain scores were the same. No patients reported any
      unintentional catheter dislodgements, falls, or dysesthesias. There were no
      readmissions of any patient in this cohort within 90 days of surgery.
      CONCLUSIONS: Ambulatory adductor canal catheters are a feasible analgesic
      modality after knee arthroplasty surgery as pain scores remained low and adverse
      events were minimal.

PMID- 27871519
TI  - Intrapleural placement of a thoracic epidural catheter in a patient with spinal
      stenosis.
AB  - Due to the close proximity of the thoracic epidural space and parietal pleura,
      pleural puncture with intrapleural catheter placement is a potential complication
      of thoracic epidural anesthesia. The authors present a case of an obese patient
      with a history of spinal stenosis that underwent thoracotomy. Repeated failed
      attempts at epidural anesthesia were complicated by intrapleural placement of the
      catheter. The patient subsequently developed clinical signs of pneumothorax and
      required urgent thoracostomy.

PMID- 27871520
TI  - Cisatracurium- and rocuronium-associated residual neuromuscular dysfunction under
      intraoperative neuromuscular monitoring and postoperative neostigmine reversal: a
      single-blind randomized trial.
AB  - BACKGROUND: Postoperative residual neuromuscular blockade (RNMB) is a common
      complication in the postanesthesia care unit (PACU), but also one of the most
      controversial issues. Many studies and trials demonstrated that some methods and
      techniques can reduce the incidence and the extent of the phenomenon. STUDY
      OBJECTIVE: To determine the incidence of RNMB in the PACU at standardized times
      after extubation with the implementation of a protocol of careful neuromuscular
      blockade management. DESIGN: Randomized, single-blinded controlled clinical
      trial. SETTING: Operating room and PACU. PATIENTS: A total of 120 patients of
      either sex with American Society of Anesthesiologists grades 1, 2, and 3, aged 18
      to 80 years were scheduled to undergo elective abdominal surgical procedures
      lasting for at least 60 minutes. INTERVENTIONS: Patients were randomized to
      receive either cisatracurium (n=60) or rocuronium (n=60) at the time of
      intubation and during surgery. Every patient received quantitative neuromuscular
      monitoring during general anesthesia. On completion of surgery, patients were
      given neostigmine 0.05 mg kg-1. Patients were extubated at a train-of-four (TOF)
      ratio>=0.9. MEASUREMENTS: TOF measurements were performed 15, 30, and 60 minutes
      after extubation. Tolerability of neuromuscular monitoring was evaluated with a
      scale from 1 to 10 (with 1 meaning no discomfort at all and 10 meaning maximal
      discomfort or pain). RESULTS: Six, 11, and 14 patients (5.0%, 9.2%, and 11.7%)
      exhibited a TOF ratio <0.9 at 15, 30, and 60 minutes after extubation,
      respectively. No statistically significant difference in the postoperative RNMB
      between cisatracurium and rocuronium was found. The median tolerability score for
      neuromuscular monitoring was 3. CONCLUSION: Careful conduction, monitoring, and
      subsequent reversal of neuromuscular block may allow for obtaining considerably
      low incidence of residual neuromuscular block. However, our trial shows that some
      mid- and long-term cases of TOF ratios <0.9 can still occur, possibly
      jeopardizing the patients' postoperative recovery.

PMID- 27871521
TI  - Functional outcome and cost-effectiveness of outpatient vs inpatient care for
      complex hind-foot and ankle surgery. A retrospective cohort study.
AB  - STUDY OBJECTIVE: To compare the postoperative functional outcome and the total
      cost associated with outpatient vs inpatient care following complex hind-foot and
      ankle surgery. DESIGN: Retrospective, cohort study. SETTING: Tertiary care
      center. PATIENTS: Forty patients, American Society of Anesthesiologists 1-3, of
      either sex undergoing elective complex hind-foot and ankle surgery (fusion,
      osteotomy, or multiple ligament repair). INTERVENTIONS: Both inpatients and
      outpatients received a continuous perineural infusion of local anesthetic for 48
      hours at the core of a multimodal analgesic regimen. Patients were
      retrospectively identified, and an outpatient cohort was matched to an inpatient
      cohort in a 1:1 ratio for age, sex, baseline functional score, and type of
      surgery. MEASUREMENTS: The primary outcome was functional outcome upon discharge
      of the surgical program as measured by the Lower Extremity Functional Score.
      Secondary outcomes were the incidence of surgical or anesthetic complications and
      the total perioperative cost of care. RESULTS: Patients in both cohorts had
      similar functional outcome on discharge of the surgical program. Analgesia was
      effective in both groups, and no complications were reported. The cost of care
      for outpatients was 54% lower than that for inpatients. CONCLUSION: This
      retrospective study suggests that outpatient care including an ambulatory
      perineural infusion of local anesthetic may be a cost-effective alternative to
      inpatient care after complex foot and ankle surgery.

PMID- 27871522
TI  - Epidural catheter blockage caused by a blood clot: is it time to change our
      practice?

PMID- 27871523
TI  - Intraoperative mandibular nerve block with peripheral nerve stimulator for
      temporomandibular joint ankylosis.
AB  - We describe the use of peripheral nerve stimulator for mandibular nerve block
      intraoperatively in a 4.5year old child with complete temporomandibular joint
      ankyloses. The block was not possible preoperatively, therefore, it was
      administered after release of ankyloses. The use of peripheral nerve stimulator
      increased the chances of a successful block. No intraoperative analgesics and
      muscle relaxants were required. Postoperative pain relief was excellent.
      Peripheral nerve stimulator is an easy way of for accurate needle tip placement
      for mandibular nerve block in patients with distorted anatomy.

PMID- 27871524
TI  - Predictors of desaturation during patient transport to the postoperative
      anesthesia care unit: an observational study.
AB  - BACKGROUND: The transport of postoperative patients to the postoperative
      anesthesia care unit (PACU) is a high-risk period for hypoxemia. The aim of this
      study was to determine risk factors for hypoxemia during transfers to the PACU.
      METHODS: An observational, prospective, monocentric, and noninterventional study
      was conducted in the University Hospital of Toulouse in 2015 during a 5-week
      period. All patients who were transferred to PACU were included. Twenty-eight
      variables related to patient, surgery, and anesthesia were recorded. Hypoxemia
      during transfer was defined as Spo2 <90%. RESULTS: Five hundred five patients
      were included. The incidence of hypoxemia during transfer was 13%. After logistic
      regression analysis, 3 risk factors for desaturation were identified: sedation
      score >2, Spo2 <96% before exiting the operating room (OR), and body mass index
      >30 kg/m2. The 72% of patients were transferred without oxygen. Most of the
      hypoxemia appears in these patients. CONCLUSION: The development of hypoxemia
      during transfer from the OR to the PACU was greater in patients who were obese,
      were more sedated, or had lower oxygen saturations upon leaving the OR. The rates
      of hypoxemia were greater among patients in whom supplemental oxygen was not
      administered. Supplemental oxygen should be considered in higher risk patients.

PMID- 27871525
TI  - A retrospective study of open thoracotomies versus thoracoscopic surgeries for
      persistent postthoracotomy pain.
AB  - OBJECTIVE: Persistent thoracotomy pain syndrome (PTPS) is a recognized
      complication and is considered to be less after video-assisted thoracoscopic
      surgery (VATS) compared with open thoracic surgery (OTS). The primary objective
      was to compare the incidence of PTPS at 6 months. Secondary objectives were to
      compare the incidence of neuropathic pain between VATS and OTS and to report
      perioperative factors associated with the development of PTPS. METHODS: This
      historical cohort study involved patient contact by a questionnaire regarding the
      presence of PTPS and its type. Patient, surgical, and analgesia factors were
      collected from health records, acute pain, and thoracic surgery databases. The
      data were analyzed using a multivariable logistic regression analysis, with
      results reported as adjusted odds ratio (OR) (95% confidence interval; P value).
      RESULTS: Of 308 patients, 130 returned their questionnaire, and 106 responses
      were analyzed. The incidence of PTPS was 35% and 54% with VATS and OTS
      respectively, with an adjusted OR, 0.33 (95% confidence interval, 0.13-0.86), P=
      .024. The percentage of neuropathic pain was 18% and 48%, with VATS and OTS
      respectively, with an adjusted OR, 0.18 (0.04-0.85), P= .031. The diagnosis of
      cancer and previous chronic pain history were observed to be significantly
      associated with PTPS. CONCLUSIONS: Our study indicates that PTPS is significantly
      more common and has a higher chance of being neuropathic with OTS. Despite being
      relatively less traumatic, VATS still carries a significant potential for PTPS. A
      diagnosis of cancer and history of previous pain are highly predictive of its
      development.

PMID- 27871527
TI  - Two lost airways and one unexpected problem: undiagnosed tracheal stenosis in a
      morbidly obese patient.
AB  - Anesthetic care of the morbidly obese is complex due to anatomic and physiologic
      alterations. Airway management in particular can be challenging. High body mass
      index is predictive of difficult ventilation and possibly difficult intubation.
      Other airway anomalies, such as tracheal stenosis, add to the complexity of
      airway management. Tracheal stenosis, a form of central airway obstruction, may
      be challenging to diagnose, especially in the obese. Comorbidities can mask the
      diagnosis and routine imaging may fail to identify the pathology. We present the
      case of a morbidly obese patient with 2 failed intubations due to difficult
      anatomy compounded with undiagnosed tracheal stenosis.

PMID- 27871528
TI  - Optimal site for the rectus sheath block.

PMID- 27871526
TI  - Risk factors for failed reactivation of a labor epidural for postpartum tubal
      ligation: a prospective, observational study.
AB  - STUDY OBJECTIVE: To determine specific risk factors that increase the failure
      rate of labor epidurals reactivated for use as a surgical block for postpartum
      tubal ligation. DESIGN: Prospective, observational study. SETTING: Labor and
      delivery suite and operating rooms at the Women and Infants Center. PATIENTS: One
      hundred patients undergoing postpartum tubal ligation with an existing labor
      epidural that is documented to be within 2 cm of initial placement. MEASUREMENTS:
      Body mass index, patient satisfaction with her epidural during labor and
      delivery, time from delivery to reactivation for tubal ligation, depth to loss of
      resistance, and the need for top-ups during labor were recorded preoperatively.
      Failure to reactivate was recorded and defined as any patient that (1) did not
      achieve a T6 level to pinprick, (2) had perceived pain (pain score >3) that
      required administration of an intravenous opioid or local anesthetic
      infiltration, or (3) required conversion to general anesthesia. MAIN RESULTS: The
      overall success rate of reactivation was 78%. Significant risk factors for
      failure to reactivate were (1) poor patient satisfaction (P = .016), (2)
      increased time from delivery to reactivation (P = .044), and (3) the need for top
      ups during labor and delivery (P = .032). CONCLUSION: Poor satisfaction score of
      the epidural during labor and delivery, increasing time from delivery to epidural
      reactivation for tubal ligation, and the need for top-ups during labor and
      delivery increase the incidence of reactivation failure. No correlation was found
      with body mass index or loss of resistance and failure to reactivate.

PMID- 27871529
TI  - Unpredictable interference of new transcranial motor-evoked potential monitor
      against the implanted pacemaker.
AB  - Recently, NuVasive NV-M5 nerve monitoring system, a new transcranial motor-evoked
      potential (TcMEP) monitor, has been introduced with the spread of flank-approach
      spinal operations such as extreme lateral interbody fusion, to prevent nerve
      damage. Conventional TcMEP monitors use changes in MEP wave patterns, such as
      amplitude and/or latency, whereas the NV-M5 nerve monitor system first measures
      the MEP baseline waveform from the transcranial-evoked potential then measures
      the electric current necessary to obtain the standard of the previous baseline
      wave pattern at subsequent monitoring times. The NV-M5 monitor determines nerve
      damage according to the increase in necessary electric current threshold. The NV
      M5 monitor also uses a local electrical stimulation mode to monitor the safety of
      setting screws into the lumbar vertebrae. In this way, various electrical
      stimulations with various durations and frequencies are used, and electrical
      noise may result in unpredictable interference with cardiac pacemakers. We
      performed anesthetic management of extreme lateral interbody fusion surgery using
      the NV-M5 in a patient with an implanted pacemaker, during which TcMEP
      stimulation caused interference with the implanted pacemaker.

PMID- 27871530
TI  - Rate vs rhythm control for postoperative atrial fibrillation. A jewel for an
      endless question?

PMID- 27871531
TI  - Klippel-Trenaunay syndrome: a rare entity with anesthesia concerns.

PMID- 27871532
TI  - Continuous quadratus lumborum block analgesia for total hip arthroplasty
      revision.

PMID- 27871533
TI  - Atypical dicrotic notch in arterial blood pressure waveform morphology.

PMID- 27871534
TI  - Laparoscopic cholecystectomy in an adult moyamoya disease case.

PMID- 27871535
TI  - Lingual Tonsil Hypertrophy: rescuing the airway with videolaryngoscopy.
AB  - Lingual tonsils are lymphatic tissues located at the base of the tongue that may
      hypertrophy causing difficulty and sometimes inability to ventilate or intubate
      during anesthesia. Routine airway assessment fails to diagnose lingual tonsil
      hypertrophy. There is limited experience with use of videolaryngoscopy in cases
      of lingual tonsil hypertrophy. We present a case of difficult airway due to
      unanticipated lingual tonsil hypertrophy successfully managed by atypical video
      laryngoscope positioning.

PMID- 27871536
TI  - Novel methods of local anesthetic delivery in the perioperative and postoperative
      setting-potential for fibrin hydrogel delivery.
AB  - The benefits of high-quality postoperative analgesia are well documented and
      include earlier mobilization, fewer respiratory and cardiovascular complications,
      and shorter hospital stay. Local anesthesia-based acute pain regimens are at
      worst equal to and at best superior to opiate-based regimens from the perspective
      of analgesia. A multimodal approach limiting opioids by combining with local
      anesthetics has additional beneficial effect on outcomes such as nausea and
      vomiting, pruritus, gastrointestinal function, respiratory complications, and
      neutrophil function. Wound catheters providing continuous infiltration of local
      anesthetics offer a rational approach to effective perioperative analgesia, but
      their use is limited by a short duration of action. There is an identified need
      for further methods to optimize longer-acting delivery of these agents. This
      article reviews current and evolving longer-acting techniques and their
      limitations with particular focus on the potential advantages of a fibrin
      hydrogel-based system.

PMID- 27871537
TI  - $1.8 Million and counting: how volatile agent education has decreased our
      spending $1000 per day.
AB  - STUDY OBJECTIVE: Volatile anesthetic agents comprise a substantial portion of
      every hospital's pharmacy budget. Challenged with an initiative to lower
      anesthetic drug expenditures, we developed an education-based intervention
      focused on reducing volatile anesthetic costs while preserving access to all
      available volatile anesthetics. When postintervention evaluation demonstrated a
      dramatic year-over-year reduction in volatile agent acquisition costs, we
      undertook a retrospective analysis of volatile anesthetic purchasing data using
      time series analysis to determine the impact of our educational initiative.
      DESIGN/SETTING: We obtained detailed volatile anesthetic purchasing data from the
      Central Supply of Wake Forest Baptist Health from 2007 to 2014 and integrated
      these data with the time course of our educational intervention. PATIENTS:
      Aggregate volatile anesthetic purchasing data were analyzed for 7 consecutive
      fiscal years. INTERVENTION: The educational initiative emphasized tissue
      partition coefficients of volatile anesthetics in adipose tissue and muscle and
      their impact on case management. MEASUREMENTS: We used an interrupted time series
      analysis of monthly cost per unit data using autoregressive integrated moving
      average modeling, with the monthly cost per unit being the amount spent per
      bottle of anesthetic agent per month. MAIN RESULTS: The cost per unit decreased
      significantly after the intervention (t=-6.73, P<.001). The autoregressive
      integrated moving average model predicted that the average cost per unit
      decreased $48 after the intervention, with 95% confidence interval of $34 to $62.
      As evident from the data, the purchasing of desflurane and sevoflurane decreased,
      whereas that of isoflurane increased. CONCLUSIONS: An educational initiative
      focused solely on the selection of volatile anesthetic agent per case
      significantly reduced volatile anesthetic expense at a tertiary medical center.
      This approach appears promising for application in other hospitals in the rapidly
      evolving, value-added health care environment. We were able to accomplish this
      with instruction on tissue partition coefficients and each agent's individual
      cost per MAC-hour delivered.

PMID- 27871538
TI  - Does dexmedetomidine cause less airway collapse than propofol when used for deep
      sedation?
AB  - STUDY OBJECTIVE: The risk of airway collapse in patients undergoing deep sedation
      is a major concern. In this study, we compared the airway patency of deep
      sedation provided by propofol with the airway patency of deep sedation provided
      by dexmedetomidine in magnetic resonance imaging (MRI) procedures. This
      comparison was done using MRI static and dynamic images and comparing these
      images to baseline after sevoflurane induction. DESIGN: After institutional
      review board approval, children who were scheduled for MRI procedures were given
      an inhalation induction, had intravenous access established, and were randomized
      to receive either dexmedetomidine 1-MUg/kg load followed by 1-MUg/(kg h) infusion
      or propofol infusion at 300 MUg/(kg min) reduced to 250-MUg/(kg min) infusion. MR
      images were then obtained. Airway patency and collapse were assessed at the level
      of the posterior midtongue in the axial and sagittal planes. The degree of airway
      collapse was assessed by determining the percent change in the airway caliber
      from its minimum to maximum value. After conclusion of the MRI procedure, the
      study patients were immediately observed by a blinded observer to determine their
      level of sedation according to the Ramsey sedation scale. SETTING: MRI scanner at
      Women and Children's Hospital of Buffalo. PATIENTS: Forty children between the
      ages of 3 and 7 years. INTERVENTION: Comparison of the utilization of propofol
      against dexmedetomidine infusions for deep sedation to determine the degree of
      airway collapse. MEASUREMENTS: Magnetic resonance images were then obtained using
      a 1.5-T GE Excite 12.0 scanner. Airway patency and collapse were assessed at the
      level of the posterior midtongue in the axial and sagittal planes. The degree of
      airway collapse was assessed by determining the percent change in the airway
      caliber from its minimum to maximum value. After conclusion of the MRI procedure,
      the study patients were immediately observed by a blinded observer to determine
      their level of sedation according to the Ramsey sedation scale. MAIN RESULTS: Our
      study demonstrated no difference in airway collapse between dexmedetomidine-based
      deep sedation and propofol-based deep sedation following sevoflurane induction.
      CONCLUSION: In deep sedation, which is commonly associated with a loss of airway
      tone, it may not matter which of these intravenous study agents are used.
      Intravenous sedation with propofol or dexmedetomidine appears to produce the same
      effect on the pediatric airway.

PMID- 27871539
TI  - Liberal or restrictive fluid management during elective surgery: a systematic
      review and meta-analysis.
AB  - This article reviews if a restrictive fluid management policy reduces the
      complication rate if compared to liberal fluid management policy during elective
      surgery. The PubMed database was explored by 2 independent researchers. We used
      the following search terms: "Blood transfusion (MESH); transfusion need; fluid
      therapy (MESH); permissive hypotension; fluid management; resuscitation;
      restrictive fluid management; liberal fluid management; elective surgery; damage
      control resuscitation; surgical procedures, operative (MESH); wounds (MESH);
      injuries (MESH); surgery; trauma patients." A secondary search in the Medline,
      EMBASE, Web of Science, and Cochrane library revealed no additional results. We
      selected randomized controlled trials performed during elective surgeries.
      Patients were randomly assigned to a restrictive fluid management policy or to a
      liberal fluid management policy during elective surgery. The patient
      characteristics and the type of surgery varied. All but 3 studies reported
      American Society of Anaesthesiologists groups 1 to 3 as the inclusion criterion.
      The primary outcome of interest is total number of patients with a complication
      and the complication rate. Secondary outcome measures are infection rate,
      transfusion need, postoperative rebleeding, hospital stay, and renal function. In
      total, 1397 patients were analyzed (693 restrictive protocol, 704 liberal
      protocol). Meta-analysis showed that in the restrictive group as compared with
      the liberal group, fewer patients experienced a complication (relative risk [RR],
      0.65; 95% confidence interval [CI], 0.55-0.78). The total complication rate (RR,
      0.57; 95% CI, 0.52-0.64), risk of infection (RR, 0.62; 95% CI, 0.48-0.79), and
      transfusion rate (RR, 0.81; 95% CI, 0.66-0.99) were also lower. The postoperative
      rebleeding did not differ in both groups: RR, 0.76 (95% CI, 0.28-2.06). We
      conclude that compared with a liberal fluid policy, a restrictive fluid policy in
      elective surgery results in a 35% reduction in patients with a complication and
      should be advised as the preferred fluid management policy.

PMID- 27871540
TI  - Comparison of the effects of Truview PCDTM video laryngoscopy and Macintosh blade
      direct laryngoscopy in geriatric patients.
AB  - STUDY OBJECTIVE: To compare the effects of Truview PCDTM video laryngoscopy (TVL)
      and Macintosh blade direct laryngoscopy (MDL) on hemodynamic responses observed
      during laryngoscopy and orotracheal intubation conditions in geriatric patients.
      DESIGN: Randomized prospective study. SETTING: Operating room. PATIENTS: One
      hundred patients in the risk group American Society of Anesthesiologists I to III
      aged 65 years and older underwent elective surgery under general anesthesia.
      INTERVENTIONS: This prospective study was performed between January 2014 and
      February 2015 after institutional ethics committee approval. Patients were
      randomly allocated to 2 groups, namely, TVL and MDL. MEASUREMENTS: Hemodynamic
      parameters, modified Cormack-Lehane grade, intubation period, and preoperative
      examination (age, sex, American Society of Anesthesiologists, modified Mallampati
      test score, and thyromental and sternomental distances) of patients were
      evaluated. MAIN RESULTS: There were no statistically significant differences in
      hemodynamic responses (heart rates and mean arterial pressure) between the 2
      groups (P>.05). The median intubation period in the TVL group was significantly
      higher than observed in the MDL group (t=4.594; P<.05). The laryngoscopy views in
      TVL group were better than the views in MDL group. The Cormack-Lehane grade in
      the TVL group was lower when compared to the MDL group. CONCLUSION: The TVL
      system does not provide significant hemodynamic response sparing or shorten
      orotracheal intubation times when compared to MDL in geriatric patients.

PMID- 27871541
TI  - Transapical transcatheter aortic valve implantation performed with a retrolaminar
      block.

PMID- 27871542
TI  - Severe respiratory depression and bradycardia before induction of anesthesia and
      onset of Takotsubo cardiomyopathy after cardiopulmonary resuscitation.
AB  - A 69-year-old woman undergoing treatment for hypertension and epilepsy was
      scheduled to undergo cataract surgery. All preoperative examination results were
      within normal limits. Despite being tense, she walked to the operating room.
      Approximately 2 minutes after an intravenous line was established by an
      anesthesia resident, severe hypoxia and bradycardia developed, and she lost
      consciousness. Cardiopulmonary resuscitation was initiated immediately, and after
      1 minute, she regained consciousness, and her breathing and circulation
      recovered. After admission to the intensive care unit, emergency coronary
      angiography was performed. The blood flow in all the coronary arteries was
      normal. However, a decrease in the apical left ventricular wall motion and an
      increase in the basal wall motion were observed. Based on these findings,
      Takotsubo cardiomyopathy was diagnosed. The wall motion gradually improved and
      the patient was discharged from the hospital on postoperative day 15. The
      respiratory depression and bradycardia were thought to be due to an inadvertent
      bolus of remifentanil. We surmised that the patient had received a slight amount
      of retained medication when the anesthesia resident established the intravenous
      line, which caused severe respiratory depression. It is important to note that
      adverse effects such as severe respiratory depression and bradycardia can be
      caused by even small doses of remifentanil.

PMID- 27871543
TI  - Soft palate trauma induced during GlideScope intubation.
AB  - The GlideScope (GVL; Saturn Biomedical Systems, Burnaby, British Columbia,
      Canada) is a rigid indirect video laryngoscope device that facilitates exposure
      of the larynx for placement of the endotracheal tube. This blade also reduces the
      requirement for anterior displacement of the tongue. A unique feature is the
      acutely angled blade which provides an improved glottic view. Herein, we present
      2 instances of soft palate trauma, a rare oropharyngeal complication linked to
      GlideScope use. In the first case, the GlideScope was used for pedagogical
      purposes for intubation in a knee surgery. In the second case, GlideScope was
      used to secure the airway of an obese patient with a Mallampati class 3 airway
      and, therefore, presumed difficult intubation. Use of the GlideScope requires
      less lifting force (approximately 0.5-1.5 kg) than direct laryngoscopy to achieve
      visualization of the glottis, so less traction is applied to soft tissue.
      However, meticulous care must be taken even by experienced operators to ensure
      correct use to decrease the incidence of oropharyngeal injuries, especially in
      patients with difficult airways. Increased vigilance makes the GlideScope an
      invaluable tool despite its potential complications.

PMID- 27871544
TI  - Comparison of anesthetic management and outcomes of robot-assisted vs pure
      laparoscopic radical prostatectomy.
AB  - STUDY OBJECTIVE: Limited data are available regarding the anesthetic management
      and outcome of patients undergoing pure laparoscopic radical prostatectomy (LRP)
      and robotic-assisted LRP (RALP). Therefore, our primary objective was to compare
      the anesthetic management between these 2 groups. Our secondary objective was to
      determine the incidence of adverse outcomes associated with RALP, which requires
      an extreme Trendelenburg position. DESIGN: A retrospective observational study.
      SETTING: University teaching hospital. PATIENTS: A total of 223 men, consisting
      of 97 LRP patients and 126 RALP patients, treated during a 3-year period (January
      2010-December 2012) were retrospectively studied. INTERVENTIONS: None.
      MEASUREMENTS: Information on patient demographics, type of anesthesia,
      anesthetic/pneumoperitoneum/surgical times, intraoperative fluids and blood
      products, estimated blood loss, intraoperative and postoperative opioid use,
      postoperative analgesic consumption, length of stay in the postanesthesia care
      unit, postoperative complications, and hospital stays was collected and compared.
      MAIN RESULTS: The estimated blood loss was higher in LRP patients than in RALP
      patients (median, 550 mL vs 200 mL; P < .001). Likewise, 24% of the LRP patients
      received intraoperative transfusions compared with 0.79% of the RALP patients (P
      < .001). The RALP patients had a longer anesthesia time (median, 276 vs 259
      minutes; P = .032) and a greater intraoperative use of opioids (P < .001). The
      incidence of complications was similar in both groups with the exception of
      postoperative nausea and vomiting, which were observed more frequently among the
      RALP patients than among the LRP patients (33% vs 16%; P = .007). CONCLUSIONS:
      This is the first report to compare the anesthetic management of RALP vs LRP.
      Anesthesiologists can expect RALP surgery to be associated with less blood loss
      and a need for fewer blood products than traditional LRP surgery. The anesthetic
      outcome of RALP was generally satisfactory except for a high incidence of
      postoperative nausea and vomiting.

PMID- 27871545
TI  - Fiberoptic-guided intubation after insertion of the i-gel airway device in
      spontaneously breathing patients with difficult airway predicted: a prospective
      observational study.
AB  - STUDY OBJECTIVE: To assess the viability of performing fiberoptic-guided
      orotracheal intubation through the i-gel airway device previously inserted in
      spontaneously breathing patients with predicted difficult airway to achieve a
      patent airway. DESIGN: Prospective observational study. SETTING: Operating room
      in a tertiary care hospital. PATIENTS: Eighty-five adult patients with at least 3
      difficult airway predictors or difficult airway management history were included.
      INTERVENTIONS: The i-gel device was inserted in spontaneous ventilation under
      oropharyngeal local anesthesia and sedation. After checking the adequate
      ventilation through the i-gel with capnography curve, general anesthesia was
      induced to introduce the endotracheal tube guided by fiberoptic bronchoscope.
      MEASUREMENTS: We recorded the i-gel insertion time (tgel), intubation time
      (tint), and O2 saturation in pulse oximetry in different moments: basal (t0),
      after 3 minutes of preoxygenation with a face mask at 100% fraction of inspired
      O2 (t1), after i-gel mask insertion (t2), and after intubation (t3). Adverse
      events during the procedure were also recorded, and patient discomfort was
      questioned. MAIN RESULTS: All patients were successfully intubated. O2 saturation
      in pulse oximetry values were (mean+/-SD): 96.9+/-1.22 (t0), 99.0+/-0.85 (t1),
      96.2+/-2.37 (t2), and 96.0+/-2.54 (t3). tgel and tint were 38.0+/-7.76 seconds
      and 36.5+/-5.55 seconds (mean+/-SD), respectively. No serious adverse events were
      recorded, and no patient suffered airway damage. Visual analogue scale for
      patient discomfort was 2 (interquartile range, 1-3). CONCLUSIONS: i-gel insertion
      in spontaneously breathing patients avoids the "cannot ventilate" scenario. The
      subsequent fiberoptic-guided intubation through the i-gel is a safe and effective
      technique. More studies might be necessary to confirm the results presented, but
      we consider that the technique described is an adequate alternative to classic
      orotracheal intubation with fiberoptic bronchoscope in spontaneous ventilation
      for certain patients with predicted difficult airway.

PMID- 27871546
TI  - The clinical utility of the Fluid Intravenous Alert monitor.

PMID- 27871547
TI  - Adductor canal block for knee surgical procedures: review article.
AB  - Adductor canal block (ACB) has recently emerged as an alternative to femoral
      nerve block for pain control after various knee procedures especially knee
      arthroplasty. In this review article, we will review the anatomy of adductor
      canal, sonoanatomy, and ultrasound-guided approach for ACB as well as review
      current evidence regarding the indications of the ACB.

PMID- 27871548
TI  - Sevoflurane attenuates platelets activation of patients undergoing lung cancer
      surgery and suppresses platelets-induced invasion of lung cancer cells.
AB  - STUDY OBJECTIVE: Platelets play a pivotal role in metastasis of tumor cells. The
      aim of this study is to explore the effects of sevoflurane and isoflurane on
      platelets activation of patients undergoing lung cancer surgery, and the effects
      of sevoflurane and isoflurane on platelets-induced invasion of lung cancer cells.
      DESIGN: Prospective and randomized study, and in vitro experiment. SETTING:
      University-affiliated teaching hospital and laboratory. PATIENTS: Forty-six
      patients scheduled for lung cancer radical surgery. INTERVENTIONS: Patients were
      randomized to two groups of 23 patients each and were received sevoflurane (group
      SEV) or isoflurane (group ISO) during surgery, respectively. In vitro, lung
      cancer cells were treated with platelets in the presence or absence anesthetics.
      MEASUREMENTS: Platelets activation were determined by detecting
      glycoproteinIIb/IIIa (GPIIb/IIIa), CD62P, and platelets aggregation rate (PAR)
      pre-, intra-, and postoperatively. Invasion ability of lung cancer cells were
      evaluated by Transwell assay. RESULTS: The levels of GPIIb/IIIa, CD62P, and PAR
      were reduced markedly in group SEV during perioperative period compared with
      group ISO. In vitro, activated platelets contributed profoundly to the invasive
      ability of lung cancer cells. Sevoflurane, but not isoflurane, inhibited
      platelets-induced invasion of lung cancer cells. Furthermore, sevoflurane
      suppressed the platelets activity in vitro. CONCLUSION: Sevoflurane attenuates
      platelets activation of patients undergoing lung cancer surgery. In vitro,
      sevoflurane suppresses platelets-induced invasion of lung cancer cells via
      decreasing platelets activity.

PMID- 27871549
TI  - A multicenter study of the analgesic effects of epidural chloroprocaine after
      lower limb orthopedic surgery.
AB  - STUDY OBJECTIVE: To investigate the effects and optimal concentration of
      chloroprocaine for epidural analgesia after lower limb orthopedic surgery.
      DESIGN: Prospective, randomized, observational, multicenter clinical study.
      SETTING: Operating room, postoperative recovery area, university hospital.
      PATIENTS: One hundred and twenty patients from 4 hospitals were enrolled and
      randomized into 5 groups after lower limb orthopedic surgery under epidural
      anesthesia with lidocaine. INTERVENTIONS: Epidural chloroprocaine mixed with
      0.4MUg/mL fentanyl was administered via a patient-controlled analgesia pump at
      the concentration of 0.6%, 0.8%, 1.0%, 1.2%, or 1.4% after the surgery.
      MEASUREMENTS: Systolic blood pressure, heart rate, visual analog score at rest
      and during activity, as well as the Bromage score at 0 minute, 30 minutes, 1
      hour, 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours after the surgery were
      recorded and compared. Use of morphine and incidence of adverse effects were also
      recorded. MAIN RESULTS: Patients given 1.2% chloroprocaine showed the lowest
      visual analog score compared with other groups. There was no significant
      difference in the Bromage score among 5 groups. The Bromage score returned to 0
      in 89.7% of the patients 48 hours after surgery. No difference in postoperative
      morphine usage, blood pressure, or heart rate was found among 5 groups.
      CONCLUSIONS: Epidural 1.2% chloroprocaine with 0.4MUg/mL fentanyl could generate
      proper analgesic effects with little influence on mobility in patients undergoing
      lower limb orthopedic surgery. In addition, it could generate a good sense and
      movement separation, facilitating the early functional training.

PMID- 27871550
TI  - Carbetocin for prevention of postcesarean hemorrhage in women with severe
      preeclampsia: a before-after cohort comparison with oxytocin.
AB  - STUDY OBJECTIVE: The aim of the study was to compare the incidence of the use of
      additional uterotonics before and after the change of carbetocin to oxytocin for
      the prevention of postpartum hemorrhage after cesarean delivery in women with
      severe preeclampsia. DESIGN: This was an observational retrospective before-and
      after study. SETTING: Operating room, postoperative recovery area. PATIENTS:
      Sixty women with severe preeclampsia undergoing cesarean delivery under spinal
      anesthesia; American Society of Anesthesiologists 3. INTERVENTIONS: Observational
      study. MEASUREMENTS: Blood pressure, heart rate, and biological data (hemoglobin,
      platelets, haptoglobin, prothrombin time index, activated partial thromboplastin
      time ratio, blood uric acid, aspartate aminotransferase, alanine
      aminotransferase, serum urea, serum creatinine, and albumin). MAIN RESULTS: The
      incidence of additional uterotonic administration in the carbetocin and oxytocin
      groups was 15% and 10%, respectively (P=.70). CONCLUSIONS: As carbetocin appears
      to be as effective and safe as oxytocin in preeclamptic women, its advantages
      make it a good uterotonic option in this particular setting.

PMID- 27871551
TI  - Exposure to anesthetic gases among operating room personnel and risk of
      genotoxicity: A systematic review of the human biomonitoring studies.
AB  - BACKGROUND AND OBJECTIVE: Anesthetic gases have been used for a long time.
      Adverse effects of anesthetic gases to occupationally exposed people have been
      well documented in the literature. Due to low solubility, these gases are rapidly
      eliminated from the human body. Nevertheless, neurotoxic, immunosuppressive,
      hepatotoxic and reproductive toxicological effects have been shown in many of the
      scientific works. However, there is no detailed systematic bio-monitoring review
      about genotoxicity risk among occupationally exposed people. We herein performed
      systematic review based on relevant studies. METHODS: This work reviews the
      published literature about the genotoxic effects of anesthetic gases among
      operating room personnel published between 1989 and September 2015. We performed
      a computerized search of articles on Pubmed, Scopus, Web of Science, and Google
      Scholar. RESULTS: Analyzed works have shown us that chromosomal aberration,
      sister chromatid exchanges, micronucleus and comet assays were the most
      frequently used genotoxicity end-points. In almost all data, occupational
      exposure to anesthetic gases has been associated with statistically significant
      increase in genotoxic damage among operating room personnel. CONCLUSION: Health
      care workers are exposed to wide variety of agents including biological, physical
      and chemical factors. Among them anesthetic gases seems to be deserve special
      attentions since their genotoxic, mutagenic activities. In addition, chronic
      exposure to all anesthetic gases instead of alone induces cumulative genotoxic
      effects.

PMID- 27871552
TI  - Preoperative depressed mood and perioperative heart rate variability in patients
      with hepatic cancer.
AB  - STUDY OBJECTIVE: How perioperative heart rate variability (HRV) indices differ
      according to the anxiety or depressed mood of patients scheduled to undergo a
      major surgical procedure for cancer. DESIGN: Prospective observational study.
      SETTING: Operating room. PATIENTS: Forty-one male patients between 40 and 70
      years of age with hepatocellular carcinoma were included in the final analysis.
      INTERVENTIONS: HRV was measured on the day before surgery (T1), impending
      anesthesia (T2), and after anesthetic induction (T3). Preoperative anxiety and
      depressed mood of all patients were evaluated using the State-Trait Anxiety
      Inventory and Self-Rating Depression Scale (SDS). MEASUREMENTS AND RESULTS: HRV
      was significantly different among T1, T2, and T3. At T2, high frequency (HF)
      (normalized units of HF [nuHF]) was decreased and low frequency (LF) (normalized
      units of LF) and LF/HF were increased compared with those at T1 and T3. In the
      subgroup analysis between high and low SDS groups, high SDS group showed
      significantly decreased nuHF (P = .035), increased nuLF (P = .039), and increased
      LF/HF (P = .020) compared to low SDS group at T1. However, these values at T2 and
      T3 were not different between 2 groups. In analysis within the groups, low SDS
      group showed significant differences in nuHF, nuLF, and LF/HF among T1, T2, and
      T3 (P < .05, respectively), but no changes in these values were observed in high
      SDS group among the 3 different time points. CONCLUSIONS: HRV decreased
      significantly immediately before anesthesia and recovered to baseline with
      anesthetic induction. Preoperative, more depressed patients showed increased
      sympathetic tone at baseline and blunted response to impending anesthesia on the
      HRV measurements.

PMID- 27871553
TI  - Fascia iliaca block associated only with deep sedation in high-risk patients,
      taking P2Y12 receptor inhibitors, for intramedullary femoral fixation in
      intertrochanteric hip fracture: a series of 3 cases.
AB  - OBJECTIVE: We present a series of 3 cases in which the impact in outcome was,
      first of all, related to the capacity to offer early and safer treatment to some
      hip fracture high-risk patients using a fascia iliaca block (FIB; ropivacaine
      0,5% 20 cc and mepivacaine 1,3% 15 cc, given 30 minutes before incision)
      associated only with deep sedation, contributing to better practice and outcome.
      CASE REPORTS: All elderly patients were American Society of Anesthesiologists IV
      patients, under P2Y12 receptor inhibitors, suffering from an intertrochanteric
      fracture, and purposed for intramedullary femoral fixation (IMF). All patients
      have been managed successfully through a deep sedation using a low-dose infusion
      of propofol and bolus of fentanyl without face mask ventilation, supraglottic
      device placement, or endotracheal intubation after an FIB. Bispectral index was
      always greater than 75, and no CO2 retention or respiratory depression was
      present. No signs of pain or hemodynamic instability were observed. CONCLUSIONS:
      In these cases, surgery would be postponed if the choice was neuroaxial
      anesthesia, particularly because of P2Y12 receptor inhibitors' effect. FIB
      puncture site is distal to the fracture and incision site, but proximal local
      anesthetic migration through the interfascial planes allows for constant block of
      femoral nerve and lateral cutaneous of femur nerve and, less constantly, block of
      obturator. FIB may reduce the risk of perineural hematoma associated with several
      injections in nerve vicinity of different lumbar plexus branches. Frequently,
      indications for extramedullary or IMF are overlapping, but IMF is associated with
      less blood loss and may be managed using a low anesthetic depth if an FIB is
      done, increasing safety. This way, these less invasive surgical techniques
      combined with an adjusted anesthetic technique may have a crucial role in high
      risk patients, particularly if taking P2Y12 receptor inhibitors. In these cases
      of IMF, surgical manipulation of sciatic and/or inferior subcostal nerves
      territories was managed with systemic analgesia and deep sedation.

PMID- 27871554
TI  - Evaluation of pH on removed tracheal tubes after general anesthesia: a
      prospective observational study.
AB  - STUDY OBJECTIVE: Aspiration pneumonia is a complication of tracheal intubation
      and mechanical ventilation. We hypothesized that tracheal tubes removed after
      anesthesia that have an acidic pH may reflect latent regurgitation of gastric
      fluid. DESIGN: A prospective observational study. SETTING: Operating room.
      PATIENTS: Tracheal tubes removed from 200 patients (age range, 20-85 years) who
      had undergone general anesthesia with tracheal intubation and gastric tube
      placement were examined. MEASUREMENTS: To detect regurgitated gastric fluid on
      the tubes, we measured pH at 5 different points along the tubes and in the water
      in which the removed tracheal tubes were immersed. MAIN RESULTS: Of the 200
      removed tracheal tubes, 5 had an acidic pH. The tubes were used in patients who
      were in the prone (1 patients) or head-down (4 patients) position while under
      anesthesia. The incidence of acidic pH was significantly higher in patients who
      were in the prone (1/32) or head-down (4/56) position, compared with those in the
      supine (0/92) or lateral (0/20) position (P<.05). CONCLUSION: Acidic pH was found
      on about 2.5% of removed tracheal tubes. These tubes were used in patients who
      were in the prone or head-down position during general anesthesia, although they
      did not exhibit significant aspiration symptom. Anesthesiologists should be aware
      of the inherent risk of gastric fluid regurgitation when their patients undergo
      general anesthesia in these positions.

PMID- 27871555
TI  - Anesthetic implications for patients with Segawa syndrome.
AB  - STUDY OBJECTIVE: To characterize the perioperative course of patients with Segawa
      syndrome undergoing anesthetic management. DESIGN: Retrospective observational
      case study. SETTING: Large tertiary medical center. PATIENTS: Patients with
      Segawa syndrome who underwent procedures requiring anesthetic management at our
      institution from January 1, 2004, through July 31, 2015. MEASUREMENTS: The health
      records of patients with Segawa syndrome. MAIN RESULTS: Twelve patients with
      Segawa syndrome underwent 25 procedures requiring anesthetic management,
      including 20 operations with general anesthesia. Succinylcholine was administered
      in 6 cases and nondepolarizing neuromuscular blockers in 5 cases, all without
      adverse effects. Perioperative complications were unrelated to anesthetic
      management or underlying neurologic condition. In 16 operations, the patients
      were receiving levodopa therapy at the time of the procedure. CONCLUSIONS: In
      this cohort, patients with Segawa syndrome tolerated the anesthetic management,
      including neuromuscular blocker administration. Although these patients are
      frequently receiving levodopa therapy, no associated complications were noted.

PMID- 27871556
TI  - An analysis of green discoloration of urine caused by propofol infusion.
AB  - BACKGROUND: Propofol is a short-acting, intravenous sedative-hypnotic agent that
      is widely used for the induction and maintenance of general anesthesia and
      sedation. An uncommon adverse effect of propofol is green discoloration of the
      urine, which has been reported not only under general anesthesia but also with
      sedation. Although it is assumed that the phenolic derivatives of propofol can
      cause green discoloration of the urine, the actual origin remains unknown. The
      aim of this report was to identify the origin of the green discoloration of the
      urine using liquid chromatography-mass spectrometry (LC-MS). CLINICAL FEATURES:
      The patient, a 51-year-old man, was scheduled for his oral surgery under general
      anesthesia using propofol. Postoperatively, the color of his urine was observed
      to be green. We compared and analyzed both the green urine and the normal urine
      using LC-MS. CONCLUSION: We experienced a case of a patient with green
      discoloration of the urine after general anesthesia using propofol. Although LC
      MS analysis showed 2 unique peaks in the green urine at 490 and 590 nm, obvious
      causes were not revealed.

PMID- 27871557
TI  - Effect of adjunctive dexmedetomidine on postoperative intravenous opioid
      administration in patients undergoing thyroidectomy in an ambulatory setting.
AB  - STUDY OBJECTIVE: Two of the most feared complications for patients undergoing
      thyroid surgery are pain and postoperative nausea and vomiting. Thyroidectomy is
      considered high risk for postoperative nausea and vomiting, and recent studies
      have looked at adjuncts to treat pain, limit narcotic use, "fast-track" the
      surgical process, and enhance recovery without compromising the patient's safety.
      One such perioperative medication of interest is dexmedetomidine (Dex), a
      centrally acting alpha-2 agonist that has been associated with reducing pain and
      postoperative opioid consumption. Our aim was to examine the effectiveness of Dex
      as an adjunctive intraoperative medication to reduce postoperative narcotic
      requirements in patients undergoing outpatient thyroid surgery. DESIGN, SETTING,
      PATIENTS AND INTERVENTION: After obtaining approval from the Institutional Review
      Board at The University of Texas MD Anderson Cancer Center, we searched the
      electronic medical record for the period October 2013 to March 2015 to identify
      patients who had undergone thyroid surgery in the ambulatory setting under
      general anesthesia. MEASUREMENTS AND MAIN RESULTS: A total of 71 patients
      underwent thyroidectomy or thyroid lobectomy in the outpatient setting. Of the
      patients receiving adjunctive Dex, a lower proportion (50%, n=9) received
      postoperative intravenous opioids when compared with control patients (79%, n=42)
      (P=.017). One patient (5%) in the Dex group required rescue postoperative
      antiemetics as compared to 11 (21%) patients in the control group (P=.273).
      CONCLUSIONS: Our data suggest that intraoperative use of Dex reduced narcotic
      administration in the postoperative period among study population patients
      undergoing thyroidectomy.

PMID- 27871558
TI  - COMBIPECS, the single-injection technique of pectoral nerve blocks 1 and 2: a
      case series.
AB  - Ultrasound-guided Pecs block can provide perioperative analgesia for breast
      surgery. A single-injection technique (COMBIPECS) combines both Pecs 1 and Pecs 2
      blocks in a single needle pass. This technique saves time and is equally
      effective as the modified Pecs block which uses 2 needle passes. We present a
      case series of 21 patients who received the COMBIPECS block as a part of
      multimodal analgesia for breast cancer surgery. The block was administered before
      the surgery after induction of general anesthesia. The patients needed minimal
      intraoperative analgesics and remained pain free in the postoperative period up
      to 24 hours after surgery.

PMID- 27871559
TI  - Quality of recovery from anesthesia of patients undergoing balanced or total
      intravenous general anesthesia. Prospective randomized clinical trial.
AB  - STUDY OBJECTIVES: The aim of the present study was to assess the quality of
      recovery from anesthesia of patients subjected to otorhinolaryngological (ORL)
      surgery under balanced or total intravenous general anesthesia by means of
      Quality of Recovery-40 (QoR-40) questionnaire. DESIGN: Prospective randomized
      clinical trial. SETTING: The setting is at an operating room, a postoperative
      recovery area, and a hospital ward. PATIENTS: One-hundred thirty American Society
      of Anesthesiologists physical status I or II patients scheduled to undergo
      general anesthesia for ORL interventions under remifentanil, in combination with
      sevoflurane (balanced technique) or propofol (total intravenous anesthesia).
      MEASUREMENTS: Occurrence of nausea, vomiting, body temperature less than 36
      degrees C, and length of stay in the postanesthesia care unit were recorded. The
      QoR-40 was administered by an investigator blind to group allocation 24 hours
      after surgery. The quality of recovery, as assessed by the score on the QoR-40,
      was compared between the groups. MAIN RESULTS: There is no difference regarding
      the QoR-40 score among intravenous and inhalation anesthesia groups (190.5 vs
      189.5, respectively; P=.33). Similarly, among the 5 dimensions of the QoR-40, the
      scores were comparable between the groups. Incidence of hypothermia (P=.58),
      nauseas or vomits (P=.39), and length of surgery (P=.16) were similar among
      groups. The evaluation of pain intensity (P=.80) and dose of morphine use in the
      postanesthesia care unit (P=.4) was also comparable between groups. CONCLUSIONS:
      The quality of recovery from anesthesia assessed based on the patients'
      perception did not differ between the ones subjected to either inhalation or
      intravenous general anesthesia for ORL surgery based on QoR-40 questionnaire
      assessment.

PMID- 27871560
TI  - Anesthesiology residents' perception of educational environment: comparison
      between different years of training.
AB  - STUDY OBJECTIVES: To assess whether the year of residency in anesthesiology is
      associated with residents' overall perceptions of the learning environment and to
      evaluate the association between year of residency and each of the five domains
      of the Dundee Ready Education Environment Measure (DREEM) survey. DESIGN: Cross
      sectional study. SETTING: Residency program of anesthesiology at the Cleveland
      Clinic. SUBJECTS AND INTERVENTION: Residents of anesthesiology at the Cleveland
      Clinic were invited to complete the DREEM questionnaire and a demographic survey.
      MEASUREMENTS: We assessed whether year of residency was associated with the
      overall standardized DREEM questionnaire score using linear regression. We also
      assessed the associations between year of residency and each of the 5 DREEM
      questionnaire domains using separate linear regression models. RESULTS: Of the 60
      residents invited to complete the DREEM questionnaire, 49 (82%) completed it.
      There was no association between year of residency and overall DREEM score (P =
      .21), students' perception of teaching (P = .38), students' perceptions of
      teachers (P = .28), students' academic self-perceptions (P = .03), students'
      perceptions of atmosphere (P = .65), or students' social self-perceptions (P =
      .08). The primary outcome was assessed using a significance criterion of 0.05,
      whereas each secondary outcome was assessed using a significance criterion of
      0.01 for secondary analyses (ie, 0.05/5, Bonferroni). CONCLUSION: Resident's
      perception of the learning environment in the anesthesiology residency program of
      the Cleveland Clinic is on the positive side, as measured by the DREEM
      questionnaire. We found no association between the year of training and the DREEM
      questionnaire overall score. Furthermore, we found no association between year of
      residency and any of the subscores for the 5 DREEM domains. There is room for
      improvement, especially in the area of self-perception.

PMID- 27871561
TI  - Perioperative fluid therapy: defining a clinical algorithm between insufficient
      and excessive.
AB  - In the perioperative scenario, adequate fluid and volume therapy is a challenging
      task. Despite improved knowledge on the physiology of the vascular barrier
      function and its respective pathophysiologic disturbances during the
      perioperative process, clear-cut therapeutic principles are difficult to
      implement. Neglecting the physiologic basis of the vascular barrier and the
      cardiovascular system, numerous studies proclaiming different approaches to fluid
      and volume therapy do not provide a rationale, as various surgical and patient
      risk groups, and different fluid regimens combined with varying hemodynamic
      measures and variable algorithms led to conflicting results. This review refers
      to the physiologic basis and answers questions inseparably conjoined to a
      rational approach to perioperative fluid and volume therapy: Why does fluid get
      lost from the vasculature perioperatively? Whereto does it get lost? Based on
      current findings and rationale considerations, which fluid replacement algorithm
      could be implemented into clinical routine?

PMID- 27871562
TI  - Anesthetizing a child for a large compressive mediastinal mass with distraction
      techniques and music therapies as the sole agents.
AB  - Anesthetic management of the child with an anterior mediastinal mass is
      challenging. The surgical/procedural goal typically is to obtain a definitive
      tissue diagnosis to guide treatment; the safest approach to anesthesia is often
      one that alters cardiorespiratory physiology the least. In severe cases, this may
      translate to little or no systemic sedatives/analgesics. Distraction techniques,
      designed to shift attention away from procedure-related pain (such as counting,
      listening to music, non-procedure-related talk), may be of great benefit,
      allowing for avoidance of pharmaceuticals. In this report, we present an approach
      in children where the anesthetic risk is deemed excessive.

PMID- 27871563
TI  - Fascia iliaca block vs intravenous fentanyl as an analgesic technique before
      positioning for spinal anesthesia in patients undergoing surgery for femur
      fractures-a randomized trial.
AB  - STUDY OBJECTIVE: Pain arising from femur fractures is of severe nature. Surgery
      for fixation of femoral fractures may be done under spinal anesthesia. We
      conducted this study to compare the analgesic efficacy of fascia iliaca
      compartment block (FICB) and intravenous fentanyl (IVF) before positioning for
      spinal anesthesia. DESIGN: Randomized controlled trial. SETTING: Operating room.
      PATIENTS AND INTERVENTIONS: Sixty patients aged 25 to 75 years, with American
      Society of Anesthesiologists status I to III, undergoing surgery for femur
      fracture were chosen for the study and randomized into 2 groups. Patients in
      group FICB received the block with 30 mL of 0.375% ropivacaine 15 minutes before
      the subarachnoid block. Patients in group IVF received intravenous fentanyl at
      0.5 MUg/kg body weight repeated up to a maximum of 3 doses. Spinal was
      administered using 12 to 15 mg of 0.5% hyperbaric bupivacaine with glucose 80
      mg/mL in patients of both groups. MEASUREMENTS: Preprocedural and postprocedural
      parameters such as visual analog scale (VAS) scores, sitting angle, quality of
      positioning, and time to perform the spinal were recorded. Patients were also
      assessed in the first 24 hours for analgesic requests. MAIN RESULTS:
      Preprocedural VAS scores were similar in both groups. The "VAS after" was 24.72+/
      15.70 mm in group FICB vs 61.22+/-18.18 mm in group IVF (P=.01). The drop in VAS
      scores was significantly more in the FICB group. Sitting angle improved
      significantly in the FICB group. (56.17 degrees +/-16.54 degrees  vs 21.38
      degrees +/-23.90 degrees ; P=.01). Patients in group FICB also needed less time
      for spinal and had better quality of positioning. Postoperative analgesic
      requirement was lesser in group FICB. CONCLUSION: Fascia iliaca block offers
      superior analgesia compared to IVF in patients with femur fracture before
      positioning for spinal anesthesia.

PMID- 27871564
TI  - Effect of remifentanil and fentanyl on postoperative cognitive function and
      cytokines level in elderly patients undergoing major abdominal surgery.
AB  - PURPOSE: Postoperative cognitive dysfunction is a frequent complication occurring
      in geriatric patients. Type of anesthesia and the patient's inflammatory response
      may contribute to postoperative cognitive dysfunction (POCD). In this prospective
      randomized double-blinded controlled study we hypothesized that intraoperative
      remifentanil may reduce immediate and early POCD compared to fentanyl and
      evaluated if there is a correlation between cognitive status and postoperative
      inflammatory cytokines level. METHODS: Six hundred twenty-two patients older than
      60 years undergoing major abdominal surgery were randomly assigned to two groups
      and treated with different opioids during surgery: continuous infusion of
      remifentanil or fentanyl boluses. Twenty-five patients per group were randomly
      selected for the quantitative determination of serum interleukin (IL)-1beta, IL
      6, and IL-10 to return to the ward and to the seventh postoperative day. RESULTS:
      Cognitive status and its correlation with cytokines levels were assessed. The
      groups were comparable regarding to POCD incidence; however, IL-6 levels were
      lower the seventh day after surgery for remifentanil group (P= .04). No
      correlation was found between POCD and cytokine levels. CONCLUSIONS: The use of
      remifentanil does not reduce POCD.

PMID- 27871565
TI  - Postoperative analgesic efficacy of fascia iliaca block versus periarticular
      injection for total knee arthroplasty.
AB  - STUDY OBJECTIVE: This study evaluated the postoperative analgesic efficacies of
      fascia iliaca block and periarticular drug injection techniques after TKA (total
      knee arthroplasty) surgeries. DESIGN: Prospective, randomized clinical trial.
      SETTING: University Teaching and Research Center. PATIENTS: Seventy-one American
      Society of Anesthesiologists (ASA) I-III patients between 48 and 70 years of age
      who underwent total knee arthroplasty were randomized. INTERVENTIONS: Tenoxicam
      (20 mg) was administered intramuscularly to both groups of patients 30 minutes
      before surgery. Patients were randomized into two groups to receive fascia iliaca
      block before the induction of anesthesia (Group FI) or periarticular drug
      injection during the surgery (Group PI). All surgeries were performed under
      general anesthesia using standard techniques. Postoperative analgesia was
      provided with patient-controlled intravenous morphine. MEASUREMENTS: Total
      morphine consumption was the primary outcome measure and was recorded
      postoperatively at 1, 2, 6, 12 and 24 hours. Pain levels at rest and on movement
      (knee flexion) were evaluated using the Visual Analogue Scale (VAS) and recorded
      at the same time points. Patients' demographics, rescue analgesic demands, side
      effects, hemodynamics, and satisfaction scores were also recorded. MAIN RESULTS:
      The groups had similar VAS scores both at rest and on movement (P>.05). However,
      the amount of cumulative morphine and use at each follow-up period was higher in
      Group PI (P<.0001). The groups did not differ significantly in rescue analgesic
      use or side effects, such as nausea/vomiting, hemodynamic variables, and patient
      satisfaction scores (P>.05). CONCLUSIONS: Fascia iliaca block may be used as an
      alternative method to periarticular injection, and it effectively reduces the
      amount of morphine used to relieve post-TKA pain.

PMID- 27871566
TI  - Known difficult airway in a patient with pheochromocytoma: a case report.
AB  - : The manipulation of an airway is always a critical moment in the anesthetic
      management of patients with pheochromocytoma due to the high incidence of
      undesirable hemodynamic events in relation with the stimulus represented by the
      laryngoscopy. A known difficult airway in which it is necessary to carry out an
      orotracheal intubation while preserving spontaneous ventilation subjects the
      patient to a stressful situation. The objective is to obtain an acceptable level
      of comfort and sedation avoiding respiratory depression (Anesthesiol Clin
      2015;33:233-40). In this case, we describe the management of a known difficult
      airway in a patient with a pheochromocytoma and a personal history of arterial
      hypertension and chronic obstructive pulmonary disease who underwent orotracheal
      intubation with spontaneous ventilation with Airtraq and with dexmedetomidine as
      the only sedative agent. CONCLUSION: Dexmedetomidine is a useful drug for
      sedation during orotracheal intubation with spontaneous ventilation in a patient
      with pheochromocytoma and a chronic respiratory pathology (Chin Med J (Engl)
      2015;128:3143-3148, J Clin Anesth 2007; 19:370-373).

PMID- 27871567
TI  - Intraoperative medications associated with hemodynamically significant
      anaphylaxis.
AB  - STUDY OBJECTIVE: To facilitate the identification of drugs and patient factors
      associated with hemodynamically significant anaphylaxis. DESIGN: Using an
      existing database containing complete perioperative records, instances of
      hemodynamically significant anaphylaxis were identified using a physiologic and
      treatment-based screening algorithm. All cases were manually reviewed by 2
      clinicians, with a third adjudicating disagreements, and confirmed cases were
      matched 3:1 with control cases. Intraoperative medications given in instances of
      hemodynamically significant anaphylaxis and patient risk factors were compared
      with control cases. SETTING: University of Michigan Hospital, a large, tertiary
      care hospital. PATIENTS: All adult patients undergoing surgery between January 1,
      2004, and January 5, 2015. INTERVENTIONS: None. MEASUREMENTS: Incidence of
      hemodynamically significant anaphylaxis during anesthesia. Patient risk factors
      and intraoperative medications associated with hemodynamically significant
      anaphylaxis. MAIN RESULTS: Hemodynamically significant anaphylaxis occurred in 55
      of 461 986 cases (1 in 8400). Hemodynamically significant anaphylaxis occurred in
      52 patients, with 1 patient experiencing 3 instances and another patient 2
      instances. Only 1 drug was associated with an increased risk of hemodynamically
      significant anaphylaxis: protamine (odds ratio, 11.78; 95% confidence interval,
      1.40-99.26; P=.0233). No category of drugs was associated with increased risk. Of
      patient risk factors, only personal history of anaphylaxis was associated with an
      increased risk (odds ratio, 77.1; 95% confidence interval, 10.46-567.69;
      P=<.0001). Postoperative follow-up and evaluation of patients were low at our
      institution. A serum tryptase level was sent in only 49% of cases, and 41% of
      levels were positive, an overall positive rate of 20% of cases. Following
      instances of hemodynamically significant anaphylaxis, only 29% of patients were
      seen and evaluated by an allergist at our institution. CONCLUSIONS:
      Hemodynamically significant anaphylaxis is a rare complication of anesthesia,
      with an incidence consistent with the existing literature. Contrary to most
      existing literature, only protamine was associated with increased risk. A
      personal history of anaphylaxis appears to best predict risk of hemodynamically
      significant anaphylaxis.

PMID- 27871568
TI  - Discrepancy between electroencephalography and hemodynamics in a patient with
      Cockayne syndrome during general anesthesia.
AB  - Cockayne syndrome is a kind of progeria with autosomal chromosome recessiveness
      described first by Cockayne in 1936. Patients with this syndrome were
      characterized by retarded growth, cerebral atrophy, and mental retardation. We
      experienced an anesthetic management of a patient with Cockayne syndrome, who
      underwent dental treatment twice. The primary concern was discrepancy between
      electroencephalography and hemodynamics. The values of bispectral index showed a
      sharp fall to 1 digit and suppression ratio more than 40, while hemodynamics was
      stable during induction of anesthesia with sevoflurane 8%. We should pay
      attention to anesthetic depth in the central nervous system in patients with
      Cockayne syndrome. Titration of anesthetics should be performed by the
      information from electroencephalography.

PMID- 27871569
TI  - Near miss in a patient with undiagnosed Brugada syndrome: a case report and
      literature review.
AB  - Brugada syndrome is a rare genetic disorder mostly affecting young subjects
      without any underlying heart disease. Here we are describing 1 patient presented
      for gastric bypass surgery who had near cardiac arrest under general anesthesia
      for unknown reason. Postoperative investigation of this case revealed the
      diagnosis of Brugada syndrome.

PMID- 27871570
TI  - Peroperative cardiogenic shock suggesting acute coronary syndrome as initial
      manifestation of Lyme carditis.
AB  - Carditis can complicate Lyme disease in an estimated <5% of cases, and
      cardiogenic shock and severe cardiac arrhythmias are described with
      electrocardiographic abnormalities that could be suggestive of coronary
      manifestations. We report a case of severe persistent biventricular heart failure
      complicated by cardiac arrhythmias as initial manifestation of a Lyme disease
      developing peroperatively electrocardiographic abnormalities suggesting acute
      transmural myocardial infarction.

PMID- 27871572
TI  - The effects of sevoflurane and desflurane on the hemodynamics and respiratory
      functions in laparoscopic sleeve gastrectomy.
AB  - STUDY OBJECTIVES: Sleeve gastrectomy has been one of the most commonly performed
      bariatric surgery methods. The study aimed to compare the effects of 2 most
      commonly used inhalation anesthetics, sevoflurane and desflurane, on the
      peroperative hemodynamic alterations and postoperative respiratory functions in
      morbidly obese patients undergoing sleeve gastrectomy. DESIGN: Nonrandomized
      cohort. SETTINGS: Operating room, postoperative period. PATIENTS: Eighty-four
      morbidly obese patients with a body mass index greater than 40 kg/m2 who had
      scheduled to undergo sleeve gastrectomy operation were prospectively included in
      the study. INTERVENTIONS: Patients were divided into 2 groups. The maintenance of
      inhalation anesthesia was performed by sevoflurane in 1 group (sevoflurane group)
      and desflurane (desflurane group) in the other group. MEASUREMENTS: Demographic
      features, peroperative hemodynamic alterations, and the results of preoperative
      and postoperative 24th hour respiratory function tests were recorded. RESULTS:
      There was not any statistically significant difference between groups regarding
      age, sex, body mass index, anesthesia time, peroperative mean arterial pressure,
      arterial oxygen saturation, end-tidal carbon dioxide, and preoperative or
      postoperative forced expiratory volume 1/forced vital capacity ratios.
      CONCLUSION: We determined that both desflurane and sevoflurane provide similar
      intraoperative hemodynamic and early postoperative respiratory functions in
      morbidly obese patients in laparoscopic sleeve gastrectomy. Both agents can be
      regarded as alternatives for inhalation anesthetics in maintenance of anesthesia.

PMID- 27871571
TI  - Spine tumor resection among patients who refuse blood product transfusion: a
      retrospective case series.
AB  - STUDY OBJECTIVE: To describe the perioperative blood conservation strategies and
      postoperative outcomes in patients who undergo complex spinal surgery for tumor
      resection and who also refuse blood product transfusion. DESIGN: A retrospective
      case series. SETTING: A single-center, tertiary care and academic teaching
      hospital in Canada. PATIENTS: All adult patients undergoing elective major spine
      tumor resection and refusing blood product transfusion who were referred to our
      institutional Blood Utilization Program between June 1, 2004, and May 9, 2014.
      MEASUREMENTS: Data on the use of iron, erythropoietin, preoperative autologous
      blood donation, acute normovolemic hemodilution, antifibrinolytic therapy, cell
      salvage, intraoperative hypotension, and active warming techniques were
      collected. Data on perioperative hemoglobin nadir, adverse outcomes, and hospital
      length of stay were also collected. MAIN RESULTS: Four patients who refused blood
      transfusion (self-identified as Jehovah's Witnesses) underwent non-emergent
      complex spine surgery for recurrent chondrosarcoma, meningioma, metastatic
      adenocarcinoma, and metastatic malignant melanoma. All patients received 1 or
      more perioperative blood conservation strategy including preoperative iron and/or
      erythropoietin, intraoperative antifibrinolytic therapy, and cell salvage. No
      patients experienced severe perioperative anemia (average hemoglobin nadir, 124
      g/L) or anemia-related postoperative complications. CONCLUSIONS: Patients who
      decline blood product transfusion can successfully undergo major spine tumor
      resection. Careful patient selection and timely referral for perioperative
      optimization such that the risk of severe anemia is minimized are important for
      success.

PMID- 27871573
TI  - The preoperative use of field tests of exercise tolerance to predict
      postoperative outcome in intra-abdominal surgery: a systematic review.
AB  - STUDY OBJECTIVE: To assess the ability of field tests of exercise tolerance, such
      as the 6-minute walk test (6MWT) and incremental shuttle walk test (ISWT), to
      predict postoperative outcome following intra-abdominal surgery. DESIGN: A
      systematic review. SETTING: A hospital-affiliated university. MEASUREMENTS: The
      following databases were searched: AMED, CINAHL, EMBASE, PEDro, PubMed/MEDLINE,
      and The Cochrane Library. Six full-text articles were included. Data extraction
      included author, population demographics, surgery type, postoperative outcome
      measure, and field test results. The risk of bias was performed using the Quality
      in Prognosis Studies tool. RESULTS: Surgical procedures reviewed were colorectal
      (n=3), upper gastrointestinal (n=1), and intra-abdominal surgery (n=2). Field
      tests of exercise tolerance showed little ability to predict postoperative
      mortality; however, the overall rate of mortality was low. Patients achieving
      lower distances on the ISWT tended to have longer hospital stays and an increased
      risk of overall complications. The 6MWT does not appear able to predict
      postoperative cardiac or pulmonary complications; however, it may be suitable to
      predict general complications. CONCLUSIONS: Field tests may be able to predict
      postoperative outcome; however, further validation is needed. The ISWT appears to
      be the superior field test. The 6MWT and stair climb test require further
      validation to assess their predictive ability.

PMID- 27871574
TI  - Cerebral oxygenation in the beach chair position for shoulder surgery in regional
      anesthesia: impact on cerebral blood flow and neurobehavioral outcome.
AB  - STUDY OBJECTIVE: Beach chair position is considered a potential risk factor for
      central neurological events particularly if combined with low blood pressure. The
      aim of this study was to assess the impact of regional anesthesia on cerebral
      blood flow and neurobehavioral outcome. DESIGN: This is a prospective, assessor
      blinded observational study evaluating patients in the beach chair position
      undergoing shoulder surgery under regional anesthesia. SETTING: University
      hospital operating room. PATIENTS: Forty patients with American Society of
      Anesthesiologists classes I-II physical status scheduled for elective shoulder
      surgery. INTERVENTIONS: Cerebral saturation and blood flow of the middle cerebral
      artery were measured prior to anesthesia and continued after beach chair
      positioning until discharge to the postanesthesia care unit. The anesthesiologist
      was blinded for these values. Controlled hypotension with systolic blood
      pressure<=100mm Hg was maintained during surgery. MEASUREMENTS: Neurobehavioral
      tests and values of regional cerebral saturation, bispectral index, the mean
      maximal blood flow of the middle cerebral artery, and invasive blood pressure
      were measured prior to regional anesthesia, and measurements were repeated after
      placement of the patient on the beach chair position and every 20 minutes
      thereafter until discharge to postanesthesia care unit. The neurobehavioral tests
      were repeated the day after surgery. MAIN RESULTS: The incidence of cerebral
      desaturation events was 5%. All patients had a significant blood pressure drop 5
      minutes after beach chair positioning, measured at the heart as well as the
      acoustic meatus levels, when compared with baseline values (P<.05). There was no
      decrease in either the regional cerebral saturation (P=.136) or the maximal blood
      flow of the middle cerebral artery (P=.212) at the same time points. Some
      neurocognitive tests showed an impairment 24 hours after surgery (P<.001 for 2 of
      3 tests). CONCLUSIONS: Beach chair position in patients undergoing regional
      anesthesia for shoulder surgery had no major impact on cerebral blood flow and
      cerebral oxygenation. However, some impact on neurobehavioral outcome 24 hours
      after surgery was observed.

PMID- 27871575
TI  - Dose requirements of alfentanil to eliminate autonomic responses during rapid
      sequence induction with thiopental 4 mg/kg and rocuronium 0.6 mg/kg.
AB  - STUDY OBJECTIVE: Opioids are integral part of anesthesia induction, but
      information on optimal dosing is limited. We aimed to determine doses of
      alfentanil needed to eliminate increases in 5 autonomic response variables
      (plasma concentrations of epinephrine, norepinephrine and vasopressin, arterial
      blood pressure [ABP], and heart rate) during rapid-sequence induction of
      anesthesia with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. DESIGN: Prospective,
      randomized, observer-blinded, interventional clinical study. SETTING: Large
      academic institution. PATIENTS: Eighty-four healthy patients, aged 18 to 55
      years, received 1 of 7 assessor-blinded doses of alfentanil (0, 10, 20, 30, 40,
      50, and 60 MUg/kg) together with thiopental 4 mg/kg and rocuronium 0.6 mg/kg,
      administered in rapid succession (15 seconds). Laryngoscopy was initiated 40
      seconds after rocuronium, and tracheal intubation was concluded within 15 seconds
      thereafter. MEASUREMENTS: An indwelling radial artery catheter was used for
      hemodynamic monitoring and blood sampling. Relationships between alfentanil dose
      and response variables were tested with linear regression, and the influence of
      covariates (sex, body weight, and age) was determined. Alfentanil dose needed to
      prevent increases in ABP >10% above baseline with 95% probability was estimated
      with logistic regression. MAIN RESULTS: Significant relationships were determined
      between alfentanil dose and response variables. Clinically interesting influence
      of covariates was not found. Alfentanil 55 MUg/kg was needed to prevent increases
      in ABP postintubation >10% above baseline with 95% probability. One individual
      needed a bolus of vasopressor postintubation. CONCLUSIONS: Optimal control of
      autonomic responses during rapid-sequence induction was achieved with clinically
      relevant doses of alfentanil in healthy patients anesthetized with thiopental 4
      mg/kg and rocuronium 0.6 mg/kg.

PMID- 27871576
TI  - Influence of high-dose intraoperative remifentanil with intravenous ibuprofen on
      postoperative morphine consumption in patients undergoing
      pancreaticoduodenectomy: a randomized trial.
AB  - STUDY OBJECTIVE: High-dose remifentanil during surgery paradoxically increases
      postoperative pain intensity and morphine consumption. Cyclooxygenase inhibitors
      decrease prostaglandin synthesis, thereby antagonizing N-methyl-d-aspartate
      receptor activation, and may reduce hyperalgesia. This study was performed to
      evaluate whether postoperative morphine consumption increased following
      intraoperative continuous remifentanil infusion and whether this could be
      prevented by intravenous ibuprofen pretreatment. DESIGN: A randomized controlled
      study. SETTING: Single university hospital, study period from September 2014 to
      March 2015. PATIENTS: One hundred and twenty patients undergoing
      pancreaticoduodenectomy. INTERVENTIONS: After induction of anesthesia, patients
      received remifentanil target-controlled infusion (effect site concentration of 4
      ng/mL or 1 ng/mL) with or without intravenous ibuprofen (800 mg). MEASUREMENTS:
      Postoperative cumulative total morphine consumption and pain intensity were
      assessed. MAIN RESULTS: Intraoperative remifentanil use in patients receiving
      high-dose remifentanil was more than 3-fold higher than that in patients
      receiving low-dose remifentanil (2666.8 +/- 858.4 vs 872.0 +/- 233.3 MUg,
      respectively; P< .001). However, cumulative total morphine consumption at
      postoperative 1, 3, 6, 12, 24, and 48 hours did not differ among the groups.
      There were no differences among the groups in the self-administered analgesic
      dose by the patients using a controlled analgesia device, number of self
      administration attempts, numerical rating scale for pain, or analgesic side
      effects. CONCLUSIONS: We found no influence on postoperative pain after high-dose
      remifentanil in patients undergoing pancreaticoduodenectomy. Addition of
      intravenous ibuprofen did not reduce postoperative morphine consumption or pain
      intensity.

PMID- 27871577
TI  - Lack of electrical interference between spinal cord stimulators and other
      implanted electrical pulse devices.
AB  - Spinal cord stimulators (SCSs) have been used for decades to treat chronic pain.
      SCSs are often used to treat patients with chronic back pain caused by failed
      back surgery syndrome, patients with complex regional pain syndrome, or
      individuals who are not candidates for surgery. SCSs are a relative
      contraindication in patients with another electrical pulse device. We present 3
      patients who received SCS despite having another implant in place. There was no
      interaction between devices. The first case was a patient with failed back
      surgery syndrome who had an implantable cardiac defibrillator and an SCS implant.
      The second case was a nonsurgical candidate with a pacemaker who received an SCS
      to help with lower back pain due to an occupational injury. The third case was a
      patient with complex regional pain syndrome and a bladder stimulator with a
      previous SCS who received a revision to help manage the pain. In all these
      patients, pain scores significantly improved after the trial.

PMID- 27871578
TI  - Children with heart disease: Risk stratification for non-cardiac surgery.
AB  - STUDY OBJECTIVE: Children with congenital or acquired heart disease have an
      increased risk of anesthesia related morbidity and mortality. The child's
      anesthetic risk is related to the severity of their underlying cardiac disease,
      associated comorbidities, and surgical procedure. The goal of this project was to
      determine the ease of use of a preoperative risk stratification tool for
      assigning pediatric cardiac staff and to determine the relative frequency that
      children with low, moderate, and high risk cardiac disease present for non
      cardiac surgery at a tertiary pediatric hospital. DESIGN: A risk-stratification
      tool was prospectively applied to children with congenital heart disease who
      presented for non-cardiac surgery. SETTING: Perioperative. PATIENTS: We
      identified a subset of 100 children with congenital heart disease out of 2200
      children who required general anesthesia for surgical or radiological procedures
      over a 6 week period. INTERVENTIONS: A risk stratification tool was utilized to
      place the patient into low, moderate, or high risk categories to help predict
      anticipated anesthetic risk. Each grouping specified assignment of staff caring
      for the patient, clarified preoperative expectations for cardiac assessment, and
      determined if patient care could be performed at our freestanding ambulatory
      surgical center. MEASUREMENTS: Electronic perioperative records were reviewed to
      obtain demographic information, the underlying heart disease, prior cardiac
      surgery, associated conditions, anesthetic management, complications, and
      provider type. MAIN RESULTS: Approximately 4.5% of children presented with
      cardiac disease over a 6 week period. In 100 consecutive children with cardiac
      disease, 23 of the children were classified as low risk, 66 patients were
      classified as moderate risk, and 11 of the patients were classified as high risk.
      Pediatric cardiac anesthesiologists provided care to all high risk patients.
      There were no serious adverse events. CONCLUSIONS: We found this risk
      stratification method an effective method to differentiate children into low,
      moderate, and high risk categories for anesthesia planning and management.

PMID- 27871579
TI  - Undiagnosed pulmonary sequestration results in an unexplained hemorrhagic shock
      in thoracoscopic pulmonary lobectomy.
AB  - We report the first case of pulmonary sequestration which was not detected in the
      preoperative evaluation, resulting in a life-threatening hemorrhagic shock
      rapidly during the procedure of thoracoscopic pulmonary lobectomy. The
      anesthesiologists could not figure out the reason for the hemorrhagic shock in
      the surgery until an emergent laparotomy was performed. The aim of presenting
      this clinical case is to highlight the vigilance for undiagnosed pulmonary
      sequestration which lacks any specific clinical feature but has the potential to
      become an anesthetic disaster.

PMID- 27871581
TI  - Erratum to "Efficacy of palonosetron in postoperative nausea and vomiting (PONV)
      a meta-analysis" [J Clin Anesth 2016:34(459-482)].

PMID- 27871580
TI  - C1-esterase inhibitor for short-term prophylaxis in a patient with hereditary
      angioedema with normal C1 inhibitor function.
AB  - Hereditary angioedema with normal C1-esterase inhibitor (HAE-nC1INH)
      perioperative is a rare condition which could have potential disastrous
      ramifications for the anesthesiologist in the perioperative period. However,
      there is limited evidence and/or guidelines on the optimal way to manage these
      patients. We present the case of a patient with HAE-nC1INH who was successfully
      managed in the perioperative period with plasma derived C1-esterase inhibitor
      (pdC1INH). A 29-year-old woman with a diagnosis of HAE-nC1INH presented to the
      preoperative consultation in preparation for an upcoming total thyroidectomy. She
      had a 14-year history of ongoing lip and facial edema sometimes necessitating
      emergency department visitation. Close consultation with her immunologist,
      transfusion medicine specialists, and anesthesia care providers allowed for a
      preoperative plan to provide the patient adequate prophylaxis. Both pdC1INH and
      tranexamic acid were given preoperatively. The patient underwent surgery with no
      complications. A multidisciplinary team of clinical immunologists, transfusion
      medicine specialists, and anesthesiologists facilitated the successful
      perioperative management of a patient with HAE-nC1INH; pdC1INH may a suitable
      prophylactic perioperative therapy for this rare patient population.

PMID- 27871582
TI  - Glucagon-induced hypertensive emergency: a case report.
AB  - Glucagon is well acknowledged as a sphincter of Oddi relaxant for both diagnostic
      and therapeutic uses in choledocholithiasis, and an empiric treatment for beta
      blocker overdose. Although it has been implicated in inducing cardiovascular
      crises in patients with asymptomatic pheochromocytoma, adverse effects in other
      patient populations have not been characterized. This case report describes a
      patient with hypertension controlled on beta blockers who, after glucagon
      administration during an intraoperative cholangiography, experienced hypertensive
      emergency despite adequate pain control. Nitroglycerin acted as a key agent to
      decrease the patient's blood pressure as well as a secondary relaxant of the
      sphincter of Oddi. The patient had no radiographic evidence of pheochromocytoma.
      As out-of-operating room and intraoperative uses of glucagon continue to
      increase, perioperative physicians should be aware of its potential hemodynamic
      effects even in healthy populations.

PMID- 27871583
TI  - Sugammadex given for rocuronium-induced neuromuscular blockade in infants: a
      retrospective study.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and safety of sugammadex in reversing
      profound neuromuscular block induced by rocuronium in infant patients. DESIGN:
      Retrospective observational study. SETTING: University teaching hospital.
      PATIENTS: Twenty-six infants (2-12 months of age; 3-11 kg) with an American
      Society of Anesthesiologists classification I, II, or III who were scheduled to
      undergo neurosurgical procedures were included in the study. INTERVENTIONS:
      Anesthesia was induced with 5 mg/kg thiopental, 1 MUg/kg fentanyl and 0.6 mg/kg
      rocuronium. Sevoflurane was administered to all patients after intubation.
      METHODS: The neuromuscular block was monitored with acceleromyography using train
      of-four (TOF) stimuli. Patients received additional doses of rocuronium to
      maintain a deep block during surgery. If profound neuromuscular block (TOF, 0)
      persisted at the end of the surgery, 3mg/kg sugammadex was administered.
      MEASUREMENTS: The demographic data, surgeries, and anesthetic agents were
      recorded. The time from sugammadex administration to recovery of neuromuscular
      function (TOF ratio, >0.9) and complications during and after extubation were
      also recorded. MAIN RESULTS: Twenty-six infants who had a deep neuromuscular
      block (TOF, 0) at the end of surgery received 3 mg/kg sugammadex. The mean
      recovery time of the T4/T1 ratio of 0.9 was 112 seconds. No clinical evidence of
      recurarization or residual curarization was observed. CONCLUSIONS: The efficacy
      and safety of sugammadex were confirmed in infant surgical patients for reversal
      of deep neuromuscular block induced by rocuronium.

PMID- 27871584
TI  - A comparison of 3 ventilation strategies in children younger than 1 year using a
      Proseal laryngeal mask airway: a randomized controlled trial.
AB  - STUDY OBJECTIVE: To determine quantitative differences in several routinely
      measured ventilation parameters using a standardized anesthetic technique and 3
      different ventilation modalities in patients younger than 1 year with a ProSeal
      laryngeal mask airway (PLMA). DESIGN: Randomized prospective study. SETTING:
      Tertiary care pediatric hospital. PATIENTS: Thirty-nine American Society
      Anesthesiologists classifications 1 to 2, pediatric patients younger than 1 year.
      INTERVENTIONS: Three different ventilation strategies (spontaneous ventilation
      [SV], pressure support ventilation [PSV], and pressure-controlled ventilation
      [PCV]) were randomly applied to patients who underwent a standardized mask
      induction with sevoflurane/oxygen and propofol 2 mg/kg and fentanyl 2 MUg/kg
      administered intravenously followed by PLMA insertion. Patients were maintained
      on sevoflurane and N2O. MEASUREMENTS: We measured the differences in end-tidal
      CO2 (etco2), tidal volume (TV), and respiratory rate (RR) over time between SV,
      PSV, and PCV. These data were recorded at 5-minute intervals. MAIN RESULTS: etco2
      (mm Hg) was not significantly higher in the SV vs PSV (P=2.11) and SV vs PCV
      (P=.24). TV (mL/kg) was significantly lower in SV vs PSV (P<.005) and SV vs PCV
      (P<.005). RR was not significantly higher in SV vs PSV (P=.43), but was
      significantly higher in SV vs PCV (P<.005). Three patients in the SV group and 1
      patient in the PSV group failed to initiate SV and required PCV and were thus
      excluded from analysis. CONCLUSIONS: All 3 modes of ventilation using a PLMA were
      safe in children younger than 1 year. Although we did not observe a statistically
      significant increase in etco2, differences in TV and RR, and the small but
      significant incidence of apnea may make PSV or PCV more optimal ventilation
      strategies in children younger than 1 year when using a PLMA.

PMID- 27871586
TI  - Comparative effectiveness of epsilon-aminocaproic acid and tranexamic acid on
      postoperative bleeding following cardiac surgery during a national medication
      shortage.
AB  - STUDY OBJECTIVE: The aim of this study was to compare the effectiveness of
      epsilon-aminocaproic acid (epsilonACA) and tranexamic acid (TXA) in contemporary
      clinical practice during a national medication shortage. DESIGN: A retrospective
      cohort study. SETTING: The study was performed in all consecutive cardiac surgery
      patients (n=128) admitted to the cardiac-surgical intensive care unit after
      surgery at a single academic center immediately before and during a national
      medication shortage. MEASUREMENTS: Demographic, clinical, and outcomes data were
      compared by descriptive statistics using chi2 and t test. Surgical drainage and
      transfusions were compared by multivariate linear regression for patients
      receiving epsilonACA before the shortage and TXA during the shortage. MAIN
      RESULTS: In multivariate analysis, no statistical difference was found for
      surgical drain output (OR 1.10, CI 0.97-1.26, P=.460) or red blood cell
      transfusion requirement (OR 1.79, CI 0.79-2.73, P=.176). Patients receiving
      epsilonACA were more likely to receive rescue hemostatic medications (OR 1.62, CI
      1.02-2.55, P=.041). CONCLUSIONS: Substitution of epsilonACA with TXA during a
      national medication shortage produced equivalent postoperative bleeding and red
      cell transfusions, although patients receiving epsilonACA were more likely to
      require supplemental hemostatic agents.

PMID- 27871585
TI  - Optimal epidural analgesia for patients diagnosed as having gynecologic cancer
      undergoing interstitial brachytherapy.
AB  - STUDY OBJECTIVE: To determine the optimal epidural analgesia for patients
      receiving interstitial brachytherapy (ISBT) for gynecologic cancers. DESIGN:
      Retrospective analysis. SETTING: Operating room and hospital ward. PATIENTS:
      Seventy-three patients diagnosed as having gynecologic cancer and undergoing
      ISBT. INTERVENTIONS: Twelve patients received ropivacaine alone, 14 patients
      received ropivacaine with fentanyl, and 45 patients received ropivacaine with
      hydromorphone by epidural infusion. MEASUREMENTS: Numeric Rating Scale pain
      scores, amounts of nonnarcotic and narcotic pain medications used in intravenous
      morphine equivalents (IVMEs), and amount of antiemetic or antipruritic
      medications used. MAIN RESULTS: Patients receiving ropivacaine alone had higher
      pain scores the morning of day 2 (4.2 vs 1.71 vs 0.6, P=.001), the afternoon of
      day 2 (4.9 vs 2.5 vs 1.7, P=.005), and the night of day 2 (2.4 vs 2.0 vs 0.6,
      P<.001). Patients receiving opioids in their epidural had lower pain scores on
      the night of placement (P=.050), the morning of day 2 (P<.001), the afternoon of
      day 2 (P=.002), and the night of day 2 (P<.001). Patients receiving ropivacaine
      alone used more oral narcotics than did those receiving ropivacaine with fentanyl
      or ropivacaine with hydromorphone on day 3 (5.9 vs 3.8 vs 2.8mg IVME) and
      received more intravenous opioids day 1 (5.8 vs 0.0 vs 0.7mg IVME, P=.004) and
      day 2 (20.6 vs 4.8 vs 1.0mg IVME, P=.042). There were no differences in
      antiemetic or diphenhydramine usage at any time point. No epidural complications
      occurred. CONCLUSIONS: For patients receiving ISBT for gynecologic cancer,
      epidural analgesia provides safe and effective pain control. Combined modality
      epidural analgesia improves pain control and lessens oral and intravenous opioid
      requirements without increased risk of adverse effects compared with epidural
      analgesia with local anesthetic alone.

PMID- 27871587
TI  - Peripheral nerve blocks in the management of postoperative pain: challenges and
      opportunities.
AB  - Peripheral nerve blocks (PNBs) are increasingly used as a component of multimodal
      analgesia and may be administered as a single injection (sPNB) or continuous
      infusion via a perineural catheter (cPNB). We undertook a qualitative review
      focusing on sPNB and cPNB with regard to benefits, risks, and opportunities for
      optimizing patient care. Meta-analyses of randomized controlled trials have shown
      superior pain control and reductions in opioid consumption in patients receiving
      PNB compared with those receiving intravenous opioids in a variety of upper and
      lower extremity surgical procedures. cPNB has also been associated with a
      reduction in time to discharge readiness compared with sPNB. Risks of PNB,
      regardless of technique or block location, include vascular puncture and
      bleeding, nerve damage, and local anesthetic systemic toxicity. Site-specific
      complications include quadriceps weakness in patients receiving femoral nerve
      block, and pleural puncture or neuraxial blockade in patients receiving
      interscalene block. The major limitation of sPNB is the short (12-24 hours)
      duration of action. cPNB may be complicated by catheter obstruction, migration,
      and leakage of local anesthetic as well as accidental removal of catheters.
      Potential infectious complications of catheters, although rare, include local
      inflammation and infection. Other considerations for ambulatory cPNB include
      appropriate patient selection, education, and need for 24/7 availability of a
      health care provider to address any complications. The ideal PNB technique would
      have a duration of action that is sufficiently long to address the most intense
      period of postsurgical pain; should be associated with minimal risk of infection,
      neurologic complications, bleeding, and local anesthetic systemic toxicity; and
      should be easy to perform, convenient for patients, and easy to manage in the
      postoperative period.

PMID- 27871588
TI  - Novel resuscitation devices facilitate complete neurologic recovery after
      prolonged cardiac arrest in postanesthesia care unit.
AB  - Cardiac arrest in the perioperative period is associated with significant
      morbidity and mortality. Novel resuscitation devices may afford patients improved
      survival and limit neurologic injury. We report a case of cardiac arrest in the
      postanesthesia care unit that required an extensive period of cardiopulmonary
      resuscitation assisted by the ResQPOD impedance threshold device to optimize
      coronary perfusion and a LUCAS chest compression system to maintain optimal
      cardiopulmonary resuscitation while transporting the patient to the cardiac
      catheterization laboratory. Furthermore, after stabilization for an occluded left
      anterior descending artery with stent placement, an institutional hypothermia
      protocol was initiated using Thermogard XP Temperature Management system for 24
      hours.

PMID- 27871589
TI  - Trainee experience and success of urgent airway management.
AB  - BACKGROUND: There are limited data regarding emergent, non-operating room,
      intubations performed by all levels of anesthesia residents. This study was a
      large retrospective review of all non-operating room emergent intubations
      performed at a single tertiary medical center. The study evaluated the rate of
      difficult intubations by level of resident training, compared success rates for
      direct versus video laryngoscopy and evaluated the rate and success of rescue
      video laryngoscopy following failed direct laryngoscopy. METHODS: All emergent
      non-operating room intubations at a tertiary university medical center from July
      1, 2009, to August 1, 2012, were reviewed and all study data were collected from
      the medical records. Intubations were classified as being initiated with either
      direct or video methods. The total number of attempts required and the rate of
      success were compared by resident year and intubation type. RESULTS: Out of a
      total of 788 emergent intubations, 741 were performed by anesthesia residents.
      The higher level anesthesia residents (CA-2 and CA-3) had a statistically
      significant decrease in the number of attempts needed when compared to CA-1
      residents. Rate of success did not vary by resident training year, but success
      rates were higher for cases initiated with video laryngoscopy. Among direct
      initiated cases, 8% failed initial direct laryngoscopy and were then successfully
      intubated with rescue video laryngoscopy. CONCLUSIONS: During emergent, non
      operating room intubations, senior level residents used fewer attempts at
      intubations with direct laryngoscopy. Successful intubation was improved by
      beginning residents when video laryngoscopy was utilized. Complications were not
      affected by the presence of the attending anesthesiologist.

PMID- 27871590
TI  - Does nitrous oxide labor analgesia influence the pattern of neuraxial analgesia
      usage? An impact study at an academic medical center.
AB  - STUDY OBJECTIVE: To compare the rate of epidural use before and after the
      implementation of nitrous oxide (N2O). DESIGN: Data were obtained from a nursing
      database of N2O usage and our obstetric anesthesia database. We compared 8 months
      before and 8 months after the introduction of N2O. It was available 24 h/d, 7
      d/wk, consistent with neuraxial analgesia availability. Epidural utilization
      before and after introduction of N2O was compared using chi2 analysis. SETTING:
      Labor and delivery floor. MAIN RESULTS: Total number of births over the study
      period was 8539: 4315 pre-N2O and 4224 post-N2O. The rate of epidural usage was
      77% pre-N2O and 74% after N2O (P= not significant, chi2). A total of 762 patients
      used N2O. Monthly analysis showed no change in pattern of neuraxial analgesia use
      in post-N2O period compared with the pre-N2O period. CONCLUSION: The introduction
      of N2O for labor analgesia was not associated with any change in our rate of
      labor epidural utilization. Under the conditions of our study, these results
      suggest that N2O does not discourage neuraxial use for labor pain relief.

PMID- 27871591
TI  - Continuous intra-articular local anesthetic drug instillation versus
      discontinuous sciatic nerve block after total knee arthroplasty.
AB  - STUDY OBJECTIVE: Sciatic nerve block (SNB) is commonly used as adjunct to
      femoralis nerve block (FNB) to achieve high-quality pain relief after total knee
      arthroplasty (TKA). However, this combination is associated with considerable
      muscle weakness, foot drop and surgically related nerve injuries may be masked.
      The purpose of this study was to assess whether low risk continuous intra
      articular anesthetic drug instillation is an adequate alternative to SNB when
      adding to FNB after TKA. DESIGN: Retrospective investigational follow-up study.
      SETTING: University teaching hospital. Interdisciplinary postoperative anesthetic
      and orthopedic survey. PATIENTS: For this investigational analysis, 34 of 50
      consecutive patients were available. INTERVENTIONS: All patients underwent
      primary unilateral TKA. Group A (18 patients) received a continuous intra
      articular 0.33% ropivacaine (5 mL/h) instillation for the first 48 h
      postoperatively. In Group B (16 patients) a discontinuous SNB was used. Both
      groups were treated with a continuous FNB. MEASUREMENTS: Main endpoints were mean
      and maximum postoperative pain intensity levels for both anterior and posterior
      knee side, amount of postoperative administered opioid drugs, differences in
      functional outcome or hospital stay and rate of postoperative complications. MAIN
      RESULTS: Group A showed higher pain intensity levels for the posterior knee side
      (P<=.042). Merely on the second postoperative day there were no differences
      within either study group. No differences were found regarding anterior knee
      pain. Group A showed a significant higher postoperative piritramid consumption
      (P<=.007). Length of hospital stay or postoperative functional outcome was not
      significant different. Postoperative complications were not related to anesthesia
      techniques. CONCLUSIONS: SNB technique resulted in superior pain relief in
      comparison to continuous intra-articular local anesthetic drug instillation as
      adjunct to continuous FNB after TKA.

PMID- 27871593
TI  - Atropine and glycopyrrolate do not support bacterial growth-safety and economic
      considerations.
AB  - STUDY OBJECTIVE: Evaluation of bacterial growth in atropine and glycopyrrolate.
      DESIGN: Laboratory investigation. SUBJECTS AND MEASUREMENTS: Standard
      microbiological methods were used to evaluate the impact of atropine and
      glycopyrrolate on the growth of Acinetobacter baumannii, Pseudomonas aeruginosa,
      Staphylococcus aureus, and Escherichia coli. Bacterial count was checked at 0, 1,
      2, 3, 4, 6, and 24 hours. MAIN RESULTS: Atropine or glycopyrrolate did not
      support the growth of the above bacteria at any examined time at room
      temperature. Glycopyrrolate killed all of the examined strains (P < .05), whereas
      in atropine, only the clinical isolates of Staphylococcus and Acinetobacter were
      killed (P < .05). CONCLUSIONS: Drawing up atropine or glycopyrrolate at the
      beginning of the operating list and use within 24 hours if needed are a safe
      practice and do not pose infection hazard. We can also reduce hospital costs if
      we do not throw away these unused syringes following each case.

PMID- 27871592
TI  - Stability of suxamethonium in pharmaceutical solution for injection by validated
      stability-indicating chromatographic method.
AB  - STUDY OBJECTIVE: To assess the stability of pharmaceutical suxamethonium
      (succinylcholine) solution for injection by validated stability-indicating
      chromatographic method in vials stored at room temperature. METHODS: The
      chromatographic assay was achieved by using a detector wavelength set at 218 nm,
      a C18 column, and an isocratic mobile phase (100% of water) at a flow rate of 0.6
      mL/min for 5 minutes. The method was validated according to the International
      Conference on Harmonization guidelines with respect to the stability-indicating
      capacity of the method including linearity, limits of detection and quantitation,
      precision, accuracy, system suitability, robustness, and forced degradations.
      RESULTS: Linearity was achieved in the concentration range of 5 to 40 mg/mL with
      a correlation coefficient higher than 0.999. The limits of detection and
      quantification were 0.8 and 0.9 mg/mL, respectively. The percentage relative
      standard deviation for intraday (1.3-1.7) and interday (0.1-2.0) precision was
      found to be less than 2.1%. Accuracy was assessed by the recovery test of
      suxamethonium from solution for injection (99.5%-101.2%). CONCLUSION: Storage of
      suxamethonium solution for injection vials at ambient temperature (22 degrees C
      26 degrees C) for 17 days demonstrated that at least 95% of original
      suxamethonium concentration remained stable.

PMID- 27871594
TI  - Obstetric team simulation program challenges.
AB  - OBJECTIVE: To describe the challenges associated with the development and
      assessment of an obstetric emergency team simulation program. DESIGN: The goal
      was to develop a hybrid, in-situ and high fidelity obstetric emergency team
      simulation program that incorporated weekly simulation sessions on the labor and
      delivery unit, and quarterly, education protected sessions in the simulation
      center. All simulation sessions were video-recorded and reviewed. SETTING: Labor
      and delivery unit and simulation center. PARTICIPANTS: Medical staff covering
      labor and delivery, anesthesiology and obstetric residents and obstetric nurses.
      MEASUREMENTS: Assessments included an on-line knowledge multiple-choice
      questionnaire about the simulation scenarios. This was completed prior to the
      initial in-situ simulation session and repeated 3 months later, the Clinical
      Teamwork Scale with inter-rater reliability, participant confidence surveys and
      subjective participant satisfaction. A web-based curriculum comprising modules on
      communication skills, team challenges, and team obstetric emergency scenarios was
      also developed. MAIN RESULTS: Over 4 months, only 6 labor and delivery unit in
      situ sessions out of a possible 14 sessions were carried out. Four high-fidelity
      sessions were performed in 2 quarterly education protected meetings in the
      simulation center. Information technology difficulties led to the completion of
      only 18 pre/post web-based multiple-choice questionnaires. These test results
      showed no significant improvement in raw score performance from pre-test to post
      test (P=.27). During Clinical Teamwork Scale live and video assessment, trained
      raters and program faculty were in agreement only 31% and 28% of the time,
      respectively (Kendall's W=.31, P<.001 and W=.28, P<.001). Participant confidence
      surveys overall revealed confidence significantly increased (P<.05), from pre
      scenario briefing to after post-scenario debriefing. CONCLUSION: Program feedback
      indicates a high level of participant satisfaction and improved confidence yet
      further program refinement is required.

PMID- 27871595
TI  - A comparison of King Vision video laryngoscopy and direct laryngoscopy as
      performed by residents: a randomized controlled trial.
AB  - STUDY OBJECTIVE: For more than 40 years, direct laryngoscopy (DL) has been used
      to assure the airway during endotracheal intubation. The King Vision video
      laryngoscope is one of the latest devices introduced for endotracheal intubation.
      We hypothesize that, relative to direct laryngoscopy, it improves the intubation
      success rate with fewer intubation attempts and no difference in intubation time
      or complications. DESIGN: This randomized controlled clinical trial included.
      SETTING: The operating room and postanesthesia care unit of an academic hospital.
      PATIENTS: Eighty-eight patients with American Society of Anesthesiologists status
      I to II and aged >=18 years who were scheduled for elective surgery under general
      anesthesia and had no predictors of difficult airway. Patients were randomized
      (44 per group) to undergo intubation using either DL or King Vision video
      laryngoscopy (KVVL) performed by first year residents in anesthesia and intensive
      care. MEASUREMENTS: During endotracheal intubation by residents, measurements
      were success rate, number of attempts, time to intubation, visualization of the
      glottis, and presence of complications. MAIN RESULTS: Both groups had a 100%
      success rate. A greater frequency of grade 1 laryngoscopy was reported with KVVL
      (86.4%) relative to DL (59.1%) (P < .05). There were no differences in time to
      intubation or the number of attempts between the groups (P = .75 and P = .91,
      respectively). Complications after intubation were low and included oral trauma,
      esophageal intubation, and sore throat. CONCLUSIONS: The use of KVVL by residents
      with less than 1 year of training (considered nonexperts) significantly improves
      visualization of the glottis in patients without predictors of difficult airway.
      The incidence of complications was too low to draw conclusions.

PMID- 27871596
TI  - Confirmation of optimal guidewire length for central venous catheter placement
      using transesophageal echocardiography.
AB  - STUDY OBJECTIVE: Several authors have reported rare, but severe, complications
      associated with the length of the intravascular guidewire during central venous
      catheter placement, as the wire tip can cause cardiac arrhythmia or perforation
      or become trapped within the vessel. Although one report investigated the optimal
      guidewire length using fluoroscopy, few reports have precisely measured guidewire
      position using transesophageal echocardiography (TEE). Here, we investigated the
      appropriate intravascular length of a guidewire for right internal jugular vein
      approach using TEE during cardiac surgery. DESIGN: A prospective observational
      study. SETTING: Operating room. PATIENTS: Fifty-two patients undergoing elective
      cardiac surgery. MEASUREMENTS: The intravascular guidewire distance from the
      insertion site to the superior vena cava-right atrium (SVC-RA) junction was
      measured by TEE. Demographic factors (height, weight, age, etc) were recorded.
      RESULTS: The mean distance from the access site to the SVC-RA junction was 17.8+/
      1.3 cm (maximum/minimum =20.0/15.0 cm). There was a greater correlation with
      height than with weight or age. CONCLUSION: We confirmed the wire tips at all
      cases by ultrasonography. The distance using TEE was similar to that by
      fluoroscopy, but TEE was more precise. Guidewire length was weakly correlated to
      height. About 15 cm as minimum length should be considered the limit for
      guidewire length in an adult, in consideration of height, to ensure patient
      safety during central catheter placement for right internal jugular vein
      approach.

PMID- 27871597
TI  - Variability in anesthesiologists' approach to the preoperative management of
      asthmatic children.
AB  - OBJECTIVE: No consensus guidelines exist for the preoperative treatment of
      asthmatic children referred for elective surgery. We investigated the attitude of
      pediatric anesthesiologists to this issue. DESIGN: A questionnaire survey was
      conducted. SETTING: National survey. SUBJECTS: Certified Israeli pediatric
      anesthesiologists from all 24 general hospitals in Israel. MEASUREMENT: Twenty
      one questions regarding the approach to preoperative management of asthmatic
      children including 6 case scenarios with a variety of clinical situations and
      treatments of asthmatic children. The results were compared with the attitude of
      pediatric pulmonologists recently published using a similar methodology. MAIN
      RESULTS: Forty-four pediatric anesthesiologists from all 24 general hospitals in
      Israel responded. Twenty-five percent of pediatric anesthesiologists answered
      that, in addition to pediatric anesthesiologists, the primary pediatrician should
      be consulted, and 70% believed that a pediatric pulmonologists should also be
      consulted. Overall, results showed a wide variability between responders
      especially for preschool children and unstable school-aged asthmatic children for
      both disciplines. The variability referred to the use of any treatment,
      bronchodilators, inhaled corticosteroids and their combination, addition of
      systemic corticosteroids, and the length of preoperative treatment. Compared with
      pediatric pulmonologists, a better within-discipline agreement was observed by
      the pediatric anesthesiologists for stable school-aged asthmatic children with a
      lower inclination to augment preoperative treatment (P< .001). No difference was
      observed for the preschool children with asthma and for the unstable school-aged
      asthmatic child. CONCLUSIONS: A wide variability exists in pediatric
      anesthesiologists' approach to the preoperative management of asthmatic children
      for most common case scenarios. This is probably explained by the heterogeneity
      of asthma, the type of surgery, the lack of guidelines, and the paucity of data.
      Similarities as well as differences exist between pediatric anesthesiologists and
      pulmonologists. Further studies and implementation of consensus guidelines are
      needed.

PMID- 27871599
TI  - Acute, unanticipated, and prolonged superior vena cava occlusion during
      pneumonectomy.
AB  - Acute, unanticipated superior vena cava (SVC) occlusion during thoracic surgery
      can have profound hemodynamic consequences and lead to devastating neurologic
      injury. We describe the successful anesthetic management of a pneumonectomy
      complicated by prolonged intraoperative SVC occlusion lasting a total of 290
      minutes. To our knowledge, this represents the longest reported SVC occlusion
      time with no subsequent neurologic sequelae. Based on our favorable outcome and a
      review of the relevant literature, we offer a discussion of strategies for
      anesthetic management.

PMID- 27871598
TI  - Effect of endovenous lidocaine on analgesia and serum cytokines: double-blinded
      and randomized trial.
AB  - STUDY OBJECTIVE: This trial aimed to compare postoperative analgesia, opioid
      consumption, duration of ileus and hospital stay, and cytokine levels in patients
      undergoing laparoscopic cholecystectomies who received intravenous lidocaine in
      comparison with a control group. DESIGN: Prospective, longitudinal, double-blind,
      and randomized study. SETTING: Operating room and postoperative recovery area.
      PATIENTS: Forty-four American Society of Anesthesiologists I and II patients
      older than 17 years, undergoing laparoscopic cholecystectomy, under general
      anesthesia. INTERVENTIONS: The first group received intravenous lidocaine during
      the procedure until 1 hour postoperatively, whereas the second group received
      saline. Both groups received dipyrone and morphine patient-controlled analgesia.
      MEASUREMENTS: Pain was assessed by Visual Numeric Scale at rest and when coughing
      at different times after the end of the surgery. Blood samples were taken at the
      end of procedure and 24 hours later. The total morphine patient-controlled
      analgesia demand, the time for the first flatus, and the length of hospital stay
      were also recorded. MAIN RESULTS: Groups were similar in relation to sex (P= .2),
      age (P= .5), weight (P= .08), and length of surgery (P= .6). No differences were
      observed regarding the intensity of postoperative pain between the groups, either
      at rest (P= .76) or when coughing (P= .31), in morphine consumption (P= .9), and
      in the duration of ileus (P= .5) or length of hospital stay (P= .9). The
      inflammatory markers interleukin (IL)-1 (P= .02), IL-6 (P< .01), interferon-gamma
      (P< .01), and tumor necrosis factor alpha (P< .01) showed significant reduction
      in the lidocaine group against the placebo group, except IL-10 (P= .01), that,
      because of its anti-inflammatory effects, increased its concentration.
      CONCLUSIONS: Intravenous lidocaine was not able to reduce postoperative pain,
      opioid consumption, and duration of ileus or length of hospital stay. However,
      its anti-inflammatory effect was noticeable.

PMID- 27871600
TI  - Comparison of a new visual stylet (Discopo)-guided laryngeal mask airway
      placement vs conventional blind technique: a prospective randomized study.
AB  - STUDY OBJECTIVE: To compare the ease of laryngeal mask airway (LMA) insertion and
      fiberoptic view of LMA after placement using the Discopo visual stylet-guided
      insertion and conventional blind technique. DESIGN: Prospective, randomized
      controlled study. SETTING: Operating room in a university hospital. PATIENTS: One
      hundred adult patients scheduled for elective surgery under LMA general
      anesthesia were enrolled. INTERVENTIONS: Patients were randomly allocated to 2
      groups: GLMA group using a visual stylet-guided technique (n=50) and BLMA group
      using standard blind technique (n=50). Correct placement of the LMA was confirmed
      using clinical test along with fiberoptic assessment. MEASUREMENTS: Unblinded
      data were collected about the insertion time, the first attempt success rate, the
      LMA position adjustment rate, fiberoptic view of LMA anatomical position,
      hemodynamic responses, and the adverse insertion responses (bucking,
      breathholding, and laryngospasm). Blinded data were recorded about postoperative
      airway morbidity (visible blood staining on LMA at removal, sore throat, and
      hoarseness). MAIN RESULTS: Insertion was more frequently successful at the first
      attempt in GLMA than that in BLMA group (100% vs 92%; P=.041). The time taken for
      establishing effective airway was shorter in GLMA than that in BLMA (54.8 vs 62.9
      seconds; P=.001). The patients in BLMA group required more readjustment and
      reinsertion than those in GLMA group (38% vs 0%; P=.000). The fiberoptic view was
      significantly better in GLMA group (P<.001). No difference between the 2 groups
      existed regarding hemodynamic stress responses, incidences of adverse insertion
      responses, and postoperative airway morbidity. CONCLUSIONS: By direct visualizing
      the whole process of LMA insertion, the Discopo visual stylet increases the
      success rate and accuracy rate of LMA placement without increasing hemodynamic
      stress response or incidences of adverse events.

PMID- 27871601
TI  - Effects of low-dose propofol vs ketamine on emergence cough in children
      undergoing flexible bronchoscopy with sevoflurane-remifentanil anesthesia: a
      randomized, double-blind, placebo-controlled trial.
AB  - STUDY OBJECTIVE: To determine the effects of low-dose ketamine and propofol on
      cough during emergence and the recovery period when administered at emergence in
      children undergoing fiberoptic bronchoscopy for bronchoalveolar lavage (FOBL)
      with sevoflurane-remifentanil anesthesia. DESIGN: Randomized, double-blind,
      placebo-controlled trial. SETTING: Operating room, postoperative recovery area.
      PATIENTS: Sixty-eight children aged 1 to 8 years old undergoing elective
      diagnostic FOBL. INTERVENTIONS: After discontinuation of anesthetics at the end
      of FOBL, patients were randomly divided into 3 groups: in group K, children were
      administered 0.5 mg/kg of ketamine; in group P, 0.5 mg/kg of propofol; and in
      group C, 0.1 mL/kg of normal saline. MEASUREMENTS: Anesthesia time, procedure
      time, emergence time, and recovery time were recorded. Coughing and delirium
      scores were recorded as the patient fully emerged from anesthesia (time 0) and 5,
      10, 15, and 20 minutes later. MAIN RESULTS: The percentage of children with
      moderate or severe cough during emergence was similar in all groups. Mean
      delirium scores at emergence (T0) were significantly lower in group K than those
      in group P and in group C (P = .0001 and P = .02). Mean delirium score at 5
      minutes in group K (6 [5-10]) was significantly lower than that of group C (P =
      .02) and similar to that of group P. The recovery time of group K was
      significantly longer than that of group C and group P (P = .01 and P = .03,
      respectively). CONCLUSIONS: Ketamine or propofol given at the end of sevoflurane
      remifentanil general anesthesia in children undergoing FOBL did not decrease
      cough more than normal saline during the emergence period. Ketamine and propofol,
      compared to normal saline, had a beneficial effect on decreasing the incidence of
      emergence delirium. Ketamine lengthened recovery time.

PMID- 27871602
TI  - Hepatotoxicity due to red bush tea consumption: a case report.
AB  - Many conventional drugs used today, including isoniazid, dapsone, and
      acetaminophen, are well recognized culprits of hepatotoxicity. With increasing
      use of complementary and alternative medical therapies, several herbal medicines,
      such as Ma-Huang, kava, and chaparral leaf, have been implicated as hepatotoxins.
      Hepatotoxicity may be the most frequent adverse reaction to these herbal remedies
      when taken in excessive quantities. A myriad of liver dysfunctions may occur
      including transient liver enzyme abnormalities due to acute and chronic
      hepatitis. These herbal products are often overlooked as the causal etiologic
      agent during the evaluation of a patient with elevated liver function tests. We
      describe a case of hepatotoxicity due to ingestion of red bush tea diagnosed
      during preoperative assessment of a patient scheduled for laparoscopic
      appendectomy. Elevated liver enzymes and thrombocytopenia detected in the
      patient's laboratory work up confounded the initial diagnosis of acute
      appendicitis and additional investigations were required to rule out
      cholecystitis and other causes of hepatitis. Open appendectomy was done
      uneventfully under spinal anesthesia without any further deterioration of hepatic
      function.

PMID- 27871604
TI  - Enzyme spheres as novel tracing tags coupled with target-induced DNAzyme assembly
      for ultrasensitive electrochemical microRNA assay.
AB  - In this work, an ultrasensitive electrochemical microRNA detection strategy was
      developed based on porous palladium-modified horseradish peroxidase sphere
      (Pd@HRP) and target-induced assembly of DNAzyme. A highly loaded HRP sphere was
      prepared by covalent layer-by-layer assembly with CaCO3 as sacrificial template
      for the first time, and was further modified with porous Pd. Notably, Pd@HRP
      composite showed a good redox activity of HRP and electrocatalytic activity
      toward H2O2. The utilization of Pd@HRP as electrochemical signal indicator and
      enhancer to fabricate biosensor could avoid the need for additional redox
      mediator and amplify the detection sensitivity. Moreover, target recycling
      amplification was achieved by Pb2+-induced cleavage of ternary "Y" structure,
      circumventing the use of labile nuclease. Subsequent DNA concatamer synthesized
      through rolling circle amplification (RCA) reaction with cleaved hairpin probe as
      primer, hybridized with plentiful Pd@HRP-DNA probes, which led to the increased
      loading of redox-active and electrocatalytic Pd@HRP for sensitivity improvement.
      So the proposed electrochemical biosensor detected miRNA-24 down to 0.2 fM (S/N =
      3) with a wide linear range from 3 fM to 1 nM. With bifunctional Pd@HRP tag,
      DNAzyme-aided target recycle and programmable junction probe, this strategy
      possessed the advantages of high efficiency, high sensitivity, low cost and
      versatility, and thus held great promise for other low-abundance nucleic acids
      determination.

PMID- 27871603
TI  - Prophylactic phenylephrine infusion for the prevention of hypotension after
      spinal anesthesia in the elderly: a randomized controlled clinical trial.
AB  - STUDY OBJECTIVE: Hypotension frequently occurs during spinal anesthesia (SA),
      especially in the elderly. Phenylephrine is effective to prevent SA-induced
      hypotension during cesarean delivery. The objective of this study was to evaluate
      the efficacy and safety of prophylactic infusion of phenylephrine after SA for
      orthopedic surgery in the elderly. DESIGN: This prospective, randomized, double
      blind, and placebo-controlled study included 54 patients older than 60 years
      undergoing elective lower limb surgery under SA (injection of 10 mg of isobaric
      bupivacaine with 5 MUg of sufentanyl). INTERVENTION: Patients were randomized to
      group P (100-MUg/mL solution of phenylephrine solution at 1 mL/min after
      placement of SA) or the control group C (0.9% isotonic sodium chloride solution).
      The flow of the infusion was stopped if the mean arterial blood pressure (MAP)
      was higher than the baseline MAP and maintained or restarted at 1 mL/min if MAP
      was equal to or lower than the baseline MAP. Heart rate and MAP were collected
      throughout the case. MEASUREMENTS: Hypotension was defined by a 20% decrease and
      hypertension as a 20% increase from baseline MAP. Bradycardia was defined as a
      heart rate lower than 50 beats per minute. MAIN RESULTS: Twenty-eight patients
      were randomized to group P and 26 patients to group C. MAP was higher in group P
      than in group C (92 +/- 2 vs 82 +/- 2 mm Hg, mean +/- SD, P< .001). The number of
      hypotensive episodes per patient was higher in group C compared with group P (9
      [0-39] vs 1 [0-10], median [extremes], P< .01), but the number of hypotensive
      patients was similar between groups (19 [73%] vs 20 [71%], P= 1). The time to
      onset of the first hypotension was shorter in group C (3 [1-13] vs 15 [1-95]
      minutes, P= .004). The proportion of patients without hypotension (cumulative
      survival) was better in group P (P= .04). The number of hypertensive episodes per
      patient and the number of bradycardic episodes per patient were similar between
      groups (P= not significant). CONCLUSION: Prophylactic phenylephrine infusion is
      an effective method of reducing SA-induced hypotension in the elderly. Compared
      with a control group, it delays the time to onset of hypotension and decreases
      the number of hypotensive episodes per patient. More data are needed to evaluate
      clinical outcomes of such a strategy.

PMID- 27871605
TI  - Neutral hydrophilic coatings for capillary electrophoresis prepared by controlled
      radical polymerization.
AB  - In the present study, porous silica particles as well as impervious fused-silica
      wafers and capillary tubes were modified with hydrophilic polymers (hydroxylated
      polyacrylamides and polyacrylates), using a surface-confined grafting procedure
      based on atom transfer radical polymerization (ATRP) which was also surface
      initiated from alpha-bromoisobutyryl groups. Initiator immobilization was
      achieved by hydrosilylation of allyl alcohol on hydride silica followed by
      esterification of the resulting propanol-bonded surface with alpha
      bromoisobutyryl bromide. Elemental analysis, IR and NMR spectroscopies on silica
      micro-particles, atomic force microscopy, ellipsometry and profilometry on fused
      silica wafers, as well as CE on fused-silica tubes were used to characterize the
      chemically modified silica substrate at different stages. We studied the effect
      of monomer concentration as well as cross-linker on the ability of the polymer
      film to reduce electroosmosis and to prevent protein adsorption (i. e., its non
      fouling capabilities) and found that the former was rather insensitive to both
      parameters. Surface deactivation towards adsorption was somewhat more susceptible
      to monomer concentration and appeared also to be favored by a low concentration
      of the cross-linker. The results show that hydrophilic polyacrylamide and
      polyacrylate coatings of controlled thickness can be prepared by ATRP under very
      mild polymerization conditions (aqueous solvent, room temperature and short
      reaction times) and that the coated capillary tubes exhibit high efficiencies for
      protein separations (0.3-0.6 million theoretical plates per meter) as well as
      long-term hydrolytic stability under the inherently harsh conditions of capillary
      isoelectric focusing. Additionally, there was no adsorption of lysozyme on the
      coated surface as indicated by a complete recovery of the basic enzyme.
      Furthermore, since polymerization is confined to the inner capillary surface,
      simple precautions (e.g., solution filtration) during the surface modification
      process are sufficient to prevent capillary clogging.

PMID- 27871606
TI  - A novel algorithm for spectral interval combination optimization.
AB  - In this study, a new wavelength interval selection algorithm named as interval
      combination optimization (ICO) was proposed under the framework of model
      population analysis (MPA). In this method, the full spectra are divided into a
      fixed number of equal-width intervals firstly. Then the optimal interval
      combination is searched iteratively under the guide of MPA in a soft shrinkage
      manner, among which weighted bootstrap sampling (WBS) is employed as random
      sampling method. Finally, local search is conducted to optimize the widths of
      selected intervals. Three NIR datasets were used to validate the performance of
      ICO algorithm. Results show that ICO can select fewer wavelengths with better
      prediction performance when compared with other four wavelength selection
      methods, including VISSA, VISSA-iPLS, iVISSA and GA-iPLS. In addition, the
      computational intensity of ICO is also economical, benefit from fewer tune
      parameters and faster convergence speed.

PMID- 27871608
TI  - Three-step drug extraction from a single sub-millimeter segment of hair and nail
      to determine the exact day of drug intake.
AB  - Hair and nails are often used to prove drug intake over several months. However,
      it is impossible to determine the day of drug intake by conventional segmental
      analysis of bulk samples. To improve this segmental analysis, we prepared
      accurate 0.4-mm hair and 0.2-mm nail segments, which correspond to their
      respective growth rates of 1-2 days, using a tissue slicer. The aim of this study
      was to develop an efficient method to extract drugs from a single sub-millimeter
      segment of hair and nail. Hair and nails were collected from a subject who was
      administered a single dose of chlorpheniramine. Four drug extraction methods
      based on different principles such as sonication, microwaves, micropulverization,
      and alkaline dissolution were compared. Short-duration sonication followed by
      long-duration soaking served the aim. Drug extraction from a sub-millimeter
      segment was performed in three steps as follows: a segment was first washed,
      followed by sonication for 10 min soaking in the extraction solution for 24 h.
      The drug concentrations in the three extracts from each segment were quantified
      using high performance liquid chromatography-tandem mass spectrometry. Each
      concentration was displayed on a single hair strand and a single nail block so
      that the first, second, and third extracts corresponded to components on the
      surface, in the outer layer, and within the sample, respectively. The
      distribution of chlorpheniramine in a hair successfully reflected the intake
      history. This method can be used in the future to measure the detailed
      distribution of drugs in a single hair and nail.

PMID- 27871607
TI  - Highly sensitive determination of atropine using cobalt oxide nanostructures:
      Influence of functional groups on the signal sensitivity.
AB  - This study describes sensitive determination of atropine using glassy carbon
      electrodes (GCE) modified with Co3O4 nanostructures. The as-synthesised
      nanostructures were grown using cysteine (CYS), glutathione (GSH) and histidine
      (HYS) as effective templates under hydrothermal action. The obtained morphologies
      revealed interesting structural features, including both cavity-based and flower
      shaped structures. The as-synthesised morphologies were noted to actively
      participate in electro-catalysis of atropine (AT) drug where GSH-assisted
      structures exhibited the best signal response in terms of current density and
      over-potential value. The study also discusses the influence of functional groups
      on the signal sensitivity of atropine electro-oxidation. The functionalisation
      was carried with the amino acids originally used as effective templates for the
      growth of Co3O4 nanostructures. The highest increment was obtained when GSH was
      used as the surface functionalising agent. The GSH-functionalised Co3O4-modified
      electrode was utilised for the electro-chemical sensing of AT in a concentration
      range of 0.01-0.46 MUM. The developed sensor exhibited excellent working
      linearity (R2 = 0.999) and signal sensitivity up to 0.001 MUM of AT. The noted
      high sensitivity of the sensor is associated with the synergy of superb surface
      architectures and favourable interaction facilitating the electron transfer
      kinetics for the electro-catalytic oxidation of AT. Significantly, the developed
      sensor demonstrated excellent working capability when used for AT detection in
      human urine samples with strong anti-interference potential against common co
      existing species, such as glucose, fructose, cysteine, uric acid, dopamine and
      ascorbic acid.

PMID- 27871609
TI  - Doping of three-dimensional porous carbon nanotube-graphene-ionic liquid
      composite into polyaniline for the headspace solid-phase microextraction and gas
      chromatography determination of alcohols.
AB  - In this work, ionic liquid (IL, i.e. 1-hydroxyethyl-3-methylimidazolium
      tetrafluoroborate), carboxyl multiwall carbon nanotubes (MWCNTs) and reduced
      graphene oxide (rGO) were used to prepare three-dimensional porous material
      (MWCNTs-rGO-IL) by one-step self-assembly, then it was co-electrodeposited with
      polyaniline (PANI) on stainless steel wires by cyclic voltammetry. The resulting
      coating (PANI-MWCNTs-rGO-IL) was characterized by using FT-IR and scanning
      electron microscopy etc, and it showed porous structure and had high thermal
      stability. Furthermore, it was found to be very suitable for the headspace solid
      phase microextraction of alcohols (i.e. octanol, nonanol, geraniol, decanol,
      undecanol and dodecanol). By coupling with gas chromatography, wide linear ranges
      and low limits of detection (i.e. 2.2-28.3 ng L-1) were obtained for the
      alcohols. The coating also presented good repeatability and reproducibility; the
      relative standard deviations for intra-fiber and fiber-to-fiber were less than
      5.6% (n = 5) and 7.0% (n = 5) respectively. In addition, the proposed method was
      successfully applied to the determination of alcohols in tea drinks, and the
      recoveries for standards added were 85.6-114%.

PMID- 27871610
TI  - Solid-phase extraction-stepwise elution (SPE-SE) procedure for isolation of
      dissolved organic matter prior to ESI-FT-ICR-MS analysis.
AB  - Characterization of dissolved organic matter (DOM) at the molecular level will
      greatly improve our understanding of its bio-geochemical role in controlling the
      fate of contaminants in the environment, and Fourier transform ion cyclotron
      resonance mass spectrometry (FT-ICR-MS) is the most powerful analytical technique
      for this purpose. Before FT-ICR-MS analysis, isolation, desalination and
      concentration of DOM are necessary, and solid-phase extraction (SPE) is the most
      widely applied pretreatment procedure. However, some molecular information is
      lost using conventional SPE methods. Here, we propose a novel strategy of SPE
      enrichment using stepwise elution (SPE-SE). Compounds in DOM were divided into
      three fractions by this SPE-SE procedure according to their polarity and
      ionization efficiency. The diversity of DOM molecules identified by ESI-FT-ICR-MS
      using SPE-SE exceeded those using conventional SPE methods by more than 50%. This
      method is feasible and has the potential to be used as a pretreatment strategy
      for complex DOM matrixes prior to ESI-FT-ICR-MS analysis, especially for those
      rich in nitrogenous molecules, carbohydrates, lipids and/or aromatic compounds.

PMID- 27871611
TI  - Toward a suitable structural analysis of gene delivery carrier based on
      polycationic carbohydrates by electron transfer dissociation tandem mass
      spectrometry.
AB  - Polycationic carbohydrates represent an attractive class of biomolecules for
      several applications and particularly as non viral gene delivery vectors. In this
      case, the establishment of structure-biological activity relationship requires
      sensitive and accurate characterization tools to both control and achieve fine
      structural deciphering. Electrospray-tandem mass spectrometry (ESI-MS/MS) appears
      as a suitable approach to address these questions. In the study herein, we have
      investigated the usefulness of electron transfer dissociation (ETD) to get
      structural data about five polycationic carbohydrates demonstrated as promising
      gene delivery agents. A particular attention was paid to determine the influence
      of charge states as well as both fluoranthene reaction time and supplementary
      activation (SA) on production of charge reduced species, fragmentation yield,
      varying from 2 to 62%, as well as to obtain the most higher both diversity and
      intensity of fragments, according to charge states and targeted compounds. ETD
      fragmentation appeared to be mainly directed toward pending group rather than
      carbohydrate cyclic scaffold leading to a partial sequencing for building blocks
      when amino groups are close to carbohydrate core, but allowing to complete
      structural deciphering of some of them, such as those including
      dithioureidocysteaminyl group which was not possible with CID only. Such findings
      clearly highlight the potential to help the rational choice of the suitable
      analytical conditions, according to the nature of the gene delivery molecules
      exhibiting polycationic features. Moreover, our ETD-MS/MS approach open the way
      to a fine sequencing/identification of grafted groups carried on various sets of
      oligo-/polysaccharides in various fields such as glycobiology or nanomaterials,
      even with unknown or questionable extraction, synthesis or modification steps.

PMID- 27871612
TI  - An ultra-sensitive and colorimetric sensor for copper and iron based on
      glutathione-functionalized gold nanoclusters.
AB  - Here, we report an ultra-sensitive and colorimetric sensor for the detection of
      Fe3+ or Cu2+ successively using glutathione-functionalized Au nanoclusters (GSH
      AuNCs). For GSH-AuNCs can catalytically oxidize peroxidase substrates, such as 3,
      3', 5, 5'-tetramethylbenzidine (TMB), colored products are formed in the presence
      of H2O2. While upon the addition of Fe3+ or Cu2+ into the GSH-AuNCs-TMB-H2O2
      system, diverse color and absorbance of the system was obtained due to the self
      oxidation of Fe3+ and the inhibition of peroxidase-like activity of GSH-AuNCs.
      With the introduction of ethylene diamine tetraacetic acid (EDTA) or ammonium
      fluoride (NH4F) to GSH-AuNCs-TMB-H2O2+Cu2+ system or GSH-AuNCs-TMB-H2O2+Fe3+
      system respectively, a restoration of color and absorbance of system was
      realized. On the basis of above phenomenon, a colorimetric and quantitative
      approach for detecting Fe3+ and Cu2+ was developed with detection limit of 1.25 *
      10-9 M and 1.25 * 10-10 M respectively. Moreover, the concentration of Fe3+ and
      Cu2+ in human serums was also accurate quantified by this method. So this design
      strategy realized the simple and simultaneous detection of Fe3+ and Cu2+,
      suggesting significant potential in clinical diagnosis.

PMID- 27871613
TI  - Revisiting catechol derivatives as robust chromogenic hydrogen donors working in
      alkaline media for peroxidase mimetics.
AB  - Colloidal noble metal-based nanoparticles are able to catalyze oxidation of
      chromogenic substrates by H2O2, similarly to peroxidases, even in basic media.
      However, lack of robust chromogens, which work in high pH impedes their real
      applications. Herein we demonstrate the applicability of selected catechol
      derivatives: bromopyrogallol red (BPR) and pyrogallol (PG) as chromogenic
      substrates for peroxidase-like activity assays, which are capable of working over
      wide range of pH, covering also basic values. Hyperbranched polyglycidol
      stabilized gold nanoparticles (HBPG@AuNPs) were used as model enzyme mimetics.
      Efficiency of several methods of improving stability of substrates in alkaline
      media by means of selective suppression of their autoxidation by molecular oxygen
      was evaluated. In a framework of presented studies the impact of borate anion,
      applied as complexing agent for PG and BPR, on their stability and reactivity
      towards oxidation mediated by catalytic AuNPs was investigated. The key role of
      high concentration of hydrogen peroxide in elimination of non-catalytic oxidation
      of PG and improvement of optical properties of BPR in alkaline media containing
      borate was underlined. Described methods of peroxidase-like activity
      characterization with the use of BPR and PG can become universal tools for
      characterization of nanozymes, which gain various applications, among others,
      they are used as catalytic labels in bioassays and biosensors.

PMID- 27871614
TI  - Direct lead isotope analysis in Hg-rich sulfides by LA-MC-ICP-MS with a gas
      exchange device and matrix-matched calibration.
AB  - In situ Pb isotope data of sulfide samples measured by LA-MC-ICP-MS provide
      valuable geochemical information for studies of the origin and evolution of ore
      deposits. However, the severe isobaric interference of 204Hg on 204Pb and the
      lack of matrix-matched sulfide reference materials limit the precision of Pb
      isotopic analyses for Hg-rich sulfides. In this study, we observe that Hg forms
      vapor and can be completely removed from sample aerosol particles produced by
      laser ablation using a gas exchange device. Additionally, this device does not
      influence the signal intensities of Pb isotopes. The within-run precision, the
      external reproducibility and the analytical accuracy are significantly improved
      for the Hg-rich sulfide samples using this mercury-vapor-removing device. Matrix
      effects are observed when using silicate glass reference materials as the
      external standards to assess the relationship of mass fractionation factors
      between Tl and Pb in sulfide samples, resulting in a maximum deviation of ~0.20%
      for 20xPb/204Pb. Matrix-matched reference materials are therefore required for
      the highly precise and accurate Pb isotope analyses of sulfide samples. We
      investigated two sulfide samples, MASS-1 (the Unites States Geological Survey
      reference materials) and Sph-HYLM (a natural sphalerite), as potential
      candidates. Repeated analyses of the two proposed sulfide reference materials by
      LA-MC-ICP-MS yield good external reproducibility of <0.04% (RSD, k = 2) for
      20xPb/206Pb and <0.06% (RSD, k = 2) for 20xPb/204Pb with the exception of
      20xPb/204Pb in MASS-1, which provided an external reproducibility of 0.24% (RSD,
      k = 2). Because the concentration of Pb in MASS-1 (76 MUg g-1) is ~5.2 times
      lower than that in Sph-HYLM (394 +/- 264 MUg g-1). The in situ analytical results
      of MASS-1 and Sph-HYLM are consistent with the values obtained by solution MC-ICP
      MS, demonstrating the reliability and robustness of our analytical protocol.

PMID- 27871615
TI  - A homogeneous assay for highly sensitive detection of CaMV35S promoter in
      transgenic soybean by forster resonance energy transfer between nitrogen-doped
      graphene quantum dots and Ag nanoparticles.
AB  - In this work, a novel homogeneous assay for DNA quantitative analysis based on
      forster resonance energy transfer (FRET) was developed for cauliflwer mosaic
      virus 35s (CaMV35S) promoter of transgenic soybean detection. The homogenous FRET
      of fluorescence signal was fabricated by DNA hybridization with probe modified
      nitrogen-doped graphene quantum dots (NGQDs) and silver nanoparticles (AgNPs),
      which acted the donor-acceptor pairs for the first time. The highly efficient
      FRET and unique properties of the NGQDs made the proposed FRET system as a
      functionalized detection platform for labelling of DNA. Upon the recognition of
      specific target DNA (tDNA), the FRET between NGQDs and AgNPs was triggered to
      produce fluorescence quenching, which could be used for tDNA detection. The
      fabricated homogeneous FRET assay displayed a wide linear range of 0.1-500.0 nM
      and a low limit of detection 0.03 nM for the detection of CaMV35S (S/N = 3). This
      proposed biosensor revealed high specificity to detect tDNA, with acceptable
      intra-assay precision and excellent stability. This method was successfully
      applied to identify the real sample of 0.5% containing transgenic soybean, which
      achieved the most of national law regulations. This assay was further validated
      by polymerase chain reaction as the genetically modified organisms, suggesting
      that the proposed FRET system is a feasible tool for the further daily
      genetically modified organism detection.

PMID- 27871616
TI  - A sensitive fluorescence biosensor for alkaline phosphatase activity based on the
      Cu(II)-dependent DNAzyme.
AB  - Alkaline phosphatase (ALP) plays an important role in phosphate metabolism
      processes; deviation from its normal level may indicate different kinds of
      diseases, so it is highly necessary to develop some simple and sensitive methods
      to monitor the ALP level. In this study, a simple, high selective, and sensitive
      fluorescent biosensor has been proposed for ALP activity determination. The
      Cu(II)-dependent DNAzyme (Cu-Enzyme) are divided into two parts: Cu-Enzyme 1 and
      Cu-Enzyme 2, and labelled with alkyne and azido groups, respectively. The Cu
      substrate (Cu-Sub) is labelled with a FAM fluorophore (6-carboxyfluorescein) at
      the 3'-end and an additional quencher (BHQ1) at the 5'-end. The 5'-end of Cu
      Enzyme 1 is labelled with BHQ1 as well. The hybridization of the Cu-Enzyme 1 and
      Cu-Enzyme 2 with Cu-Sub strand results in the low background fluorescence signal
      because the fluorescence from FAM is quenched. The addition of ALP can hydrolyze
      AA-P into AA, which can reduce Cu(II) into Cu(I) and in turn catalyze the
      cycloaddition of Cu-Enzyme 1 and Cu-Enzyme 2 to form a modified Cu-Enzyme. Then
      the modified Cu-Enzyme catalyzes the cleavage of the Cu-Sub strands into two
      pieces. One piece containing FAM fluorophore can easily diffuse into solution and
      give off a strong fluorescence signal. The enhanced fluorescent intensity has a
      linear relationship with the ALP concentration in the range of 0.36-54.55 U L-1
      with the detection limit of 0.14 U L-1 (S/N = 3). The proposed biosensor has been
      successfully applied to detect ALP in serum samples with satisfied results.

PMID- 27871618
TI  - Coexistence of Sutton and Meyerson nevi.

PMID- 27871617
TI  - Management of cannabis-induced periodontitis via resective surgical therapy: A
      clinical report.
AB  - BACKGROUND AND OVERVIEW: There is a lack of clinical research on the potential
      effect of cannabis use on the periodontium as well as its effect on treatment
      outcomes. The aim of this case report is to illustrate the clinical presentation
      of periodontal disease in a young woman who was a chronic cannabis user, as well
      as successful treatment involving motivating the patient to quit cannabis use and
      undergo nonsurgical and surgical therapy. CASE DESCRIPTION: A 23-year-old woman
      sought care at the dental clinic for periodontal treatment. During a review of
      her medical history, the patient reported using cannabis frequently during a 3
      year period, which coincided with the occurrence of gingival inflammation. She
      used cannabis in the form of cigarettes that were placed at the mandibular
      anterior region of her mouth for prolonged periods. Localized prominent papillary
      and marginal gingival enlargement of the anterior mandible were present. The
      mandibular anterior teeth showed localized severe chronic periodontitis. The
      clinicians informed the patient about the potentially detrimental consequences of
      continued cannabis use; she was encouraged to quit, which she did. The clinicians
      performed nonsurgical therapy (scaling and root planing) and osseous surgery. The
      treatment outcome was evaluated over 6 months; improved radiographic and clinical
      results were observed throughout the follow-up period. CONCLUSIONS AND PRACTICAL
      IMPLICATIONS: Substantial availability and usage of cannabis, specifically among
      young adults, requires dentists to be vigilant about clinical indications of
      cannabis use and to provide appropriate treatments. Behavioral modification,
      nonsurgical therapy, and surgical therapy offer the potential for successful
      management of cannabis-related periodontitis.

PMID- 27871619
TI  - Doppler Ultrasound of Aneurysmal Dermatofibroma.

PMID- 27871620
TI  - Clinicopathologic Variants of Mycosis Fungoides.
AB  - Mycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma. The
      clinical course of the disease is typically characterized by progression from a
      nonspecific phase of erythematous macules to the appearance of plaques and
      ultimately, in some patients, tumors. However, numerous clinical and
      histopathologic variants of MF with specific therapeutic and prognostic
      implications have been described in recent decades. Clarification of the
      differential diagnosis can be frustrated by the wide range of clinical
      manifestations and histopathologic patterns of cutaneous infiltration,
      particularly in the early phases of the disease. In this paper, we review the
      main clinical, histopathologic, and immunohistochemical characteristics of the
      variants of MF described in the literature in order to facilitate early diagnosis
      of the disease.

PMID- 27871621
TI  - Reply.

PMID- 27871622
TI  - Unilateral BEST1-Associated Retinopathy.

PMID- 27871624
TI  - Re: Disorders of the lymphatic system of the abdomen.

PMID- 27871623
TI  - Modeling the N400 ERP component as transient semantic over-activation within a
      neural network model of word comprehension.
AB  - The study of the N400 event-related brain potential has provided fundamental
      insights into the nature of real-time comprehension processes, and its amplitude
      is modulated by a wide variety of stimulus and context factors. It is generally
      thought to reflect the difficulty of semantic access, but formulating a precise
      characterization of this process has proved difficult. Laszlo and colleagues
      (Laszlo & Plaut, 2012; Laszlo & Armstrong, 2014) used physiologically constrained
      neural networks to model the N400 as transient over-activation within semantic
      representations, arising as a consequence of the distribution of excitation and
      inhibition within and between cortical areas. The current work extends this
      approach to successfully model effects on both N400 amplitudes and behavior of
      word frequency, semantic richness, repetition, semantic and associative priming,
      and orthographic neighborhood size. The account is argued to be preferable to one
      based on "implicit semantic prediction error" (Rabovsky & McRae, 2014) for a
      number of reasons, the most fundamental of which is that the current model
      actually produces N400-like waveforms in its real-time activation dynamics.

PMID- 27871625
TI  - 3D modeling of phytoplankton seasonal variation and nutrient budget in a southern
      Mediterranean Lagoon.
AB  - A 3D coupled physical-biogeochemical model is developed and applied to Bizerte
      Lagoon (Tunisia), in order to understand and quantitatively assess its
      hydrobiological functioning and nutrients budget. The biogeochemical module
      accounts for nitrogen and phosphorus and includes the water column and upper
      sediment layer. The simulations showed that water circulation and the seasonal
      patterns of nutrients, phytoplankton and dissolved oxygen were satisfactorily
      reproduced. Model results indicate that water circulation in the lagoon is driven
      mainly by tide and wind. Plankton primary production is co-limited by phosphorus
      and nitrogen, and is highest in the inner part of the lagoon, due to the combined
      effects of high water residence time and high nutrient inputs from the boundary.
      However, a sensitivity analysis highlights the importance of exchanges with the
      Mediterranean Sea in maintaining a high level of productivity. Intensive use of
      fertilizers in the catchment area has a significant effect on phytoplankton
      biomass increase.

PMID- 27871626
TI  - Photolysis of 2,4,6-trinitrotoluene in seawater and estuary water: Impact of pH,
      temperature, salinity, and dissolved organic matter.
AB  - The influence of salinity, pH, temperature, and dissolved organic matter on the
      photolysis rate of 2,4,6-trinitrotoluene (TNT) in marine, estuary, and laboratory
      prepared waters was studied using a Suntest CPS+(r) solar simulator equipped with
      optical filters. TNT degradation rates were determined using HPLC analysis, and
      products were identified using LC/MS. Minimal or no TNT photolysis occurred under
      a 395-nm long pass filter, but under a 295-nm filter, first-order TNT degradation
      rate constants and apparent quantum yields increased with increasing salinity in
      both natural and artificial seawater. TNT rate constants increased slightly with
      increasing temperature (10 to 32 degrees C) but did not change significantly with
      pH (6.4 to 8.1). The addition of dissolved organic matter (up to 5mg/L) to
      ultrapure water, artificial seawater, and natural seawater increased the TNT
      photolysis rate constant. Products formed by TNT photolysis in natural seawater
      were determined to be 2,4,6-trinitrobenzaldehyde, 1,3,5-trinitrobenzene, 2,4,6
      trinitrobenzoic acid, and 2-amino-4,6-dinitrobenzoic acid.

PMID- 27871628
TI  - Updated evidence for left main coronary artery disease: Practice versus the
      consensus.

PMID- 27871627
TI  - Executive Leadership and Physician Well-being: Nine Organizational Strategies to
      Promote Engagement and Reduce Burnout.
AB  - These are challenging times for health care executives. The health care field is
      experiencing unprecedented changes that threaten the survival of many health care
      organizations. To successfully navigate these challenges, health care executives
      need committed and productive physicians working in collaboration with
      organization leaders. Unfortunately, national studies suggest that at least 50%
      of US physicians are experiencing professional burnout, indicating that most
      executives face this challenge with a disillusioned physician workforce. Burnout
      is a syndrome characterized by exhaustion, cynicism, and reduced effectiveness.
      Physician burnout has been shown to influence quality of care, patient safety,
      physician turnover, and patient satisfaction. Although burnout is a system issue,
      most institutions operate under the erroneous framework that burnout and
      professional satisfaction are solely the responsibility of the individual
      physician. Engagement is the positive antithesis of burnout and is characterized
      by vigor, dedication, and absorption in work. There is a strong business case for
      organizations to invest in efforts to reduce physician burnout and promote
      engagement. Herein, we summarize 9 organizational strategies to promote physician
      engagement and describe how we have operationalized some of these approaches at
      Mayo Clinic. Our experience demonstrates that deliberate, sustained, and
      comprehensive efforts by the organization to reduce burnout and promote
      engagement can make a difference. Many effective interventions are relatively
      inexpensive, and small investments can have a large impact. Leadership and
      sustained attention from the highest level of the organization are the keys to
      making progress.

PMID- 27871629
TI  - Radiography nomography: Utility of a calculator in rational preoperative decision
      making for subsolid pulmonary nodules.

PMID- 27871630
TI  - Thoracic surgery education in Canada.

PMID- 27871631
TI  - [Benefit of general anesthesia monitored by bispectral index compared with
      monitoring guided only by clinical parameters. Systematic review and meta
      analysis].
AB  - BACKGROUND: The bispectral index parameter is used to guide the titration of
      general anesthesia; however, many studies have shown conflicting results
      regarding the benefits of bispectral index monitoring. The objective of this
      systematic review with meta-analysis is to evaluate the clinical impact of
      monitoring with the bispectral index parameter. METHODS: The search for evidence
      in scientific information sources was conducted during December 2013 to January
      2015, the following primary databases: Medline/PubMed, LILACS, Cochrane, CINAHL,
      Ovid, SCOPUS and TESES. The criteria for inclusion in the study were randomized
      controlled trials, comparing general anesthesia monitored, with bispectral index
      parameter with anesthesia guided solely by clinical parameters, and patients aged
      over 18 years. The criteria for exclusion were studies involving anesthesia or
      sedation for diagnostic procedures, and intraoperative wake-up test for surgery
      of the spine. RESULTS: The use of monitoring with the bispectral index has shown
      benefits reducing time to extubation, orientation in time and place, and
      discharge from both the operating room and post anesthetic care unit. The risk of
      nausea and vomiting after surgery was reduced by 12% in patients monitored with
      bispectral index. Occurred a reduction of 3% in the risk of cognitive impairment
      postoperatively at 3 months postoperatively and 6% reduction in the risk of
      postoperative delirium in patients monitored with bispectral index. Furthermore,
      the risk of intraoperative memory has been reduced by 1%. CONCLUSION: Clinically,
      anesthesia monitoring with the BIS can be justified because it allows advantages
      from reducing the recovery time after waking, mainly by reducing the
      administration of general anesthetics as well as the risk of adverse events.

PMID- 27871632
TI  - Here/In This Issue and There/Abstract Thinking: The Inflamed Brain.

PMID- 27871633
TI  - Parental Mental Health: Addressing the Unmet Needs of Caregivers for Children
      With Autism Spectrum Disorders.

PMID- 27871634
TI  - Heritability of a General Psychopathology Factor in the Population: Potential
      Implications for Classification and Treatment.

PMID- 27871635
TI  - Challenges in Characterizing Complex Psychopathology.

PMID- 27871636
TI  - Correlates of Overweight and Obesity Among Adolescents With Bipolar Disorder in
      the National Comorbidity Survey-Adolescent Supplement (NCS-A).
AB  - OBJECTIVE: Despite substantial evidence on the prevalence and correlates of
      overweight and obesity (OW/OB) in adults with bipolar disorder (BD), little is
      known about this topic in adolescents with BD. METHOD: The method consisted of
      the National Comorbidity Survey-Adolescent Supplement, a face-to-face survey of
      mental disorders from 2001 through 2004, using a modified version of the fully
      structured World Health Organization Composite International Diagnostic
      Interview. Participants were adolescents 13 to 17 years of age, with bipolar
      disorder I or II (n = 295), major depressive disorder (n = 1,112), or controls
      with neither mood disorder (n = 8,716). Analyses examined for group differences
      in the prevalence of OW/OB and for correlates of OW/OB in the group with BD.
      RESULTS: There were no significant differences in weight categories across
      groups. OW and OB in adolescents with BD were associated with significantly
      higher lifetime rates of suicide attempt (odds ratio 3.02, 95% CI 1.11-8.24),
      physical or sexual abuse (2.82, 1.20-6.60), binge eating or bulimia (2.66, 1.13
      6.26), and conduct disorder (2.60, 1.10-6.13) in covariate-adjusted analyses. OW
      and OB also were significantly associated with seeing a professional for
      depression, being hospitalized overnight for depression, and receiving general
      medical treatment. CONCLUSION: The similar prevalence of OW/OB in adolescents
      with and without BD suggests that this potent association in adults likely
      comprises a consequence of BD or its correlates. In contrast, the strong
      association of OW/OB with proxies for depression severity, including suicide
      attempts and hospitalization, is already evident even in this young, nonclinical
      sample. Studies are warranted to determine whether early intervention of OW/OB in
      BD might optimize physical and mental health.

PMID- 27871637
TI  - Comparing Brain Morphometry Across Multiple Childhood Psychiatric Disorders.
AB  - OBJECTIVE: In both children and adults, psychiatric illness is associated with
      structural brain alterations, particularly in the prefrontal cortex (PFC).
      However, most studies compare gray matter volume (GMV) in healthy volunteers
      (HVs) to one psychiatric group. We compared GMV among youth with anxiety
      disorders, bipolar disorder (BD), disruptive mood dysregulation disorder (DMDD),
      attention-deficit/hyperactivity disorder (ADHD), and HVs. METHOD: 3-Tesla T1
      weighted magnetic resonance imaging scans were acquired in 184 youths (39
      anxious, 20 BD, 52 DMDD, 20 ADHD, and 53 HV). Voxel-based morphometry analyses
      were conducted. One-way analysis of variance tested GMV differences with whole
      brain familywise error (p < .05) correction; secondary, exploratory whole-brain
      analyses used a threshold of p < .001, >=200 voxels. Given recent frameworks
      advocating dimensional approaches in psychopathology research, we also tested GMV
      associations with continuous anxiety, irritability, and inattention symptoms.
      RESULTS: Specificity emerged in the left dorsolateral PFC (dlPFC), which differed
      among youth with BD, anxiety, and HVs; GMV was increased in youth with anxiety,
      but decreased in BD, relative to HVs. Secondary analyses revealed BD-specific GMV
      decreases in the right lateral PFC, right dlPFC, and dorsomedial PFC, and also
      anxiety-specific GMV increases in the left dlPFC, right ventrolateral PFC,
      frontal pole, and right parahippocampal gyrus/lingual gyrus. Both BD and DMDD
      showed decreased GMV relative to HVs in the right dlPFC/superior frontal gyrus.
      GMV was not associated with dimensional measures of anxiety, irritability, or
      ADHD symptoms. CONCLUSION: Both disorder-specific and shared GMV differences
      manifest in pediatric psychopathology. Some differences were specific to anxiety
      disorders, others specific to BD, and others shared between BD and DMDD. Further
      developmental research might map commonalities and differences of structure and
      function in diverse pediatric psychopathologies.

PMID- 27871639
TI  - International Comparisons of the Youth Self-Report Dysregulation Profile: Latent
      Class Analyses in 34 Societies.
AB  - OBJECTIVE: We used latent class analysis (LCA) to examine the prevalence and
      characteristics of the Dysregulation Profile (DP) based on data from the Youth
      Self-Report (YSR). The DP comprises elevated scores on the Anxious/Depressed,
      Attention Problems, and Aggressive Behavior syndromes and thus reflects
      significant problems in self-regulation of affect, attention, and behavior.
      METHOD: We examined YSR data for 38,070 adolescents (48.1% male) in 34 societies.
      Participants ranged in age from 11 to 16 years. Researchers in 31 societies used
      translations of the YSR (not in Jamaica, Australia, or the United States).
      RESULTS: The various statistical indices for good LCA model fit (entropy,
      bootstrapped parametric likelihood ratio test, adjusted Bayesian Information
      Criterion, and probability of correct assignment) were not always consistent but
      generally supported a DP class in every society. However, prevalence of the DP
      ranged from 1% to 26% and the T score syndrome profile for the DP class in many
      societies featured elevations on all scales. In every society, the DP class had
      significantly higher scores than the pooled non-DP classes on all 3 DP syndromes,
      with large d values. CONCLUSION: Because model fit, the number of classes, and
      the prevalence of the DP class varied across societies, and because the DP "3
      peak" profile was relatively uncommon, results for the DP based on adolescents'
      ratings in 34 societies must be considered as mixed.

PMID- 27871638
TI  - Single Nucleotide Polymorphism Heritability of a General Psychopathology Factor
      in Children.
AB  - OBJECTIVE: Co-occurrence of mental disorders is commonly observed, but the
      etiology underlying this observation is poorly understood. Studies in adolescents
      and adults have identified a general psychopathology factor associated with a
      high risk for different psychiatric disorders. We defined a multi-informant
      general psychopathology factor in school-aged children and estimated its single
      nucleotide polymorphism (SNP) heritability. The goal was to test the hypothesis
      that child behavioral and emotional problems are under the influence of highly
      pleiotropic common autosomal genetic variants that nonspecifically increase the
      risk for different dimensions of psychopathology. METHOD: Children from the
      Generation R cohort were repeatedly assessed between ages 6 to 8 years. Child
      behavior problems were reported by parents, teachers, and children. Confirmatory
      factor analysis estimated a general psychopathology factor across informants
      using various psychiatric problem scales. Validation of the general
      psychopathology factor was based on IQ and temperamental measures. Genome-wide
      complex trait analysis (GCTA) was used to estimate the SNP heritability (N =
      2,115). RESULTS: The general psychopathology factor was associated with lower IQ,
      higher negative affectivity, and lower effortful control, but not with surgency.
      Importantly, the general psychopathology factor showed a significant SNP
      heritability of 38% (SE = 0.16, p = .008). CONCLUSION: Common autosomal SNPs are
      pleiotropically associated with internalizing, externalizing, and other child
      behavior problems, and underlie a general psychopathology factor in childhood.

PMID- 27871640
TI  - Multidimensional Influences on Autism Symptom Measures: Implications for Use in
      Etiological Research.
AB  - OBJECTIVE: Growing awareness that symptoms of autism spectrum disorder (ASD)
      transcend multiple diagnostic categories, and major advances in the
      identification of genetic syndromes associated with ASD, have led to widespread
      use of ASD symptom measures in etiologic studies of neurodevelopmental disorders.
      Insufficient consideration of potentially confounding factors such as cognitive
      ability or behavior problems can have important negative consequences in
      interpretation of findings, including erroneous estimation of associations
      between ASD and etiologic factors. METHOD: Participants were 388 children 2 to 13
      years old with diagnoses of ASD or another neurodevelopmental disorder without
      ASD. Receiver operating characteristics methods were used to assess the influence
      of IQ and emotional and behavioral problems on the discriminative ability of 3
      widely used ASD symptom measures: the Social Responsiveness Scale (SRS), the
      Autism Diagnostic Interview-Revised (ADI-R), and the Autism Diagnostic
      Observation Schedule (ADOS). RESULTS: IQ influenced the discriminative thresholds
      of the SRS and ADI-R, and emotional and behavioral problems affected the
      discriminative thresholds of the SRS, ADI-R, and ADOS. This resulted in low
      specificity of ASD cutoffs on the SRS and ADI-R for children with intellectual
      disability without ASD (27-42%) and low specificity across all 3 instruments for
      children without ASD with increased emotional and behavioral problems (36-59%).
      Adjustment for these characteristics resulted in improved discriminative ability
      for all of the ASD measures. CONCLUSION: The findings indicate that scores on ASD
      symptom measures reflect far more than ASD symptoms. Valid interpretation of
      scores on these measures requires steps to account for the influences of IQ and
      emotional and behavioral problems.

PMID- 27871641
TI  - Longitudinal Course of Bipolar Disorder in Youth With High-Functioning Autism
      Spectrum Disorder.
AB  - OBJECTIVE: To provide the first longitudinal characterization of mood and
      psychosocial functioning in youth with comorbid bipolar (BD) and autism spectrum
      (ASD) disorders. METHOD: The Course and Outcome of Bipolar Youth study followed
      368 youth (aged 7-17 years) with DSM-IV bipolar I (BP-I), BP-II, or Not Otherwise
      Specified (NOS) for, on average, 9 years using the Longitudinal Interval Follow
      up Evaluation. This subgroup analysis compared youth with and without ASD on
      clinical presentation, percentage of time with mood symptomatology, and
      psychosocial functioning. RESULTS: Thirty youth (~8%) met DSM-IV criteria for
      Asperger's disorder or pervasive developmental disorder-NOS (referred to here as
      ASD). Lifetime worst episode severity was similar in both groups, but youth with
      both BD and ASD (BD+ASD) had elevated rates of comorbid attention
      deficit/hyperactivity and obsessive-compulsive disorders, were younger at intake,
      and had an earlier onset of mood symptoms. Over time, in both groups, the
      proportion of predominantly euthymic youth increased, and episode recurrence
      decreased. Compared to youth with BD, the clinical presentation of youth with
      BD+ASD more frequently involved distractibility, racing thoughts, depressed mood,
      social withdrawal, and low reactivity of negative mood states. ASD-related
      symptomatic differences were generally strongest early and decreased over time.
      Youth with BD+ASD had significantly greater impairment in friendships throughout
      follow-up. CONCLUSION: Youth with BD+ASD exhibit typical BD mood symptoms but
      with earlier onset, mixed symptom presentation, and additive functional
      impairments. Significant amelioration of clinical symptoms occurred over time,
      suggesting that early recognition and treatment of mood disorders in youth with
      ASD may improve clinical outcomes.

PMID- 27871642
TI  - Reduced Hemispheric Asymmetry of White Matter Microstructure in Autism Spectrum
      Disorder.
AB  - OBJECTIVE: Many past studies have suggested atypical functional and anatomical
      hemispheric asymmetries in autism spectrum disorder (ASD). However, almost all of
      these have examined only language-related asymmetries. Here, we conduct a
      comprehensive investigation of microstructural asymmetries across a large number
      of fiber tracts in ASD. METHOD: We used diffusion tensor imaging for a
      comprehensive investigation of anatomical white matter asymmetries across the
      entire white matter skeleton, using tract-based spatial statistics in 41 children
      and adolescents with ASD and a matched group of 44 typically developing (TD)
      participants. RESULTS: We found significant asymmetries in the TD group, being
      rightward for fractional anisotropy and leftward for mean diffusivity (with
      concordant asymmetries for radial and axial diffusivity). These asymmetries were
      significantly reduced in the group with ASD: in whole brain analysis for
      fractional anisotropy, and in a region where several major association and
      projection tracts travel in close proximity within occipital white matter for
      mean diffusivity, axial diffusivity, and radial diffusivity. No correlations
      between global white matter asymmetry and age or socio-communicative abilities
      were detected. CONCLUSION: Our findings in TD children and adolescents can be
      interpreted as reflecting different processing modes (more integrative in the
      right and more specialized in the left hemisphere). These asymmetries and the
      "division of labor" between hemispheres implied by them appear to be diminished
      in autism spectrum disorder.

PMID- 27871644
TI  - Neurofeedback in Attention-Deficit/Hyperactivity Disorder: Evaluation
      Difficulties.

PMID- 27871643
TI  - Neural Correlates of Reward Processing in Depressed and Healthy Preschool-Age
      Children.
AB  - OBJECTIVE: Adults and adolescents with major depressive disorder (MDD) show a
      blunted neural response to rewards. Depression has been validated in children as
      young as age 3; however, it remains unclear whether blunted response to reward is
      also a core feature of preschool-onset depression. If so, this would provide
      further validation for the continuity of the neural correlates of depression
      across the life span and would identify a potential target for treatment in young
      children. METHOD: Fifty-three 4- to 7-year-old children with depression and 25
      psychiatrically healthy 4- to 7-year-old children completed a simple guessing
      task in which points could be won or lost on each trial while event-related
      potentials (ERPs) were recorded. Psychiatric diagnosis was established using a
      preschool version of the Kiddie Schedule for Affective Disorders and Depression.
      RESULTS: Young children with depression showed a reduced differentiation between
      response to gains and losses, and this finding was driven by a blunted response
      to reward (i.e., the reward positivity [RewP]). These findings held even when
      controlling for co-occurring attention-deficit/hyperactivity disorder,
      oppositional defiant disorder, and generalized anxiety disorder. The RewP did not
      vary as a function of depression severity within the group with depression.
      CONCLUSION: Similar to adults and adolescents with depression, preschoolers with
      depression display reductions in responsivity to rewards as indexed by the RewP.
      These findings provide further evidence for continuity in the neural mechanisms
      associated with depression across the lifespan, and point to altered reward
      sensitivity as an early-emerging potential target for intervention in preschool
      onset depression. Clinical trial registration information-A Randomized Controlled
      Trial of PCIT-ED for Preschool Depression; http://clinicaltrials.gov/;
      NCT02076425.

PMID- 27871645
TI  - Neurofeedback in Attention-Deficit/Hyperactivity Disorder: Efficacy.

PMID- 27871647
TI  - One, Two, Magic.

PMID- 27871646
TI  - The European ADHD Guidelines Group replies.

PMID- 27871649
TI  - Invisible Allies: Thanking Our Reviewers.

PMID- 27871648
TI  - White Smoke: Editor's Annual Report-Volume 55, 2016.

PMID- 27871650
TI  - Transparency: Disclosure of Financial Interests.

PMID- 27871651
TI  - ERK activated by Histamine H1 receptor is anti-proliferative through spatial
      restriction in the cytosol.
AB  - Histamine, a primary mediator of allergic responses, elicits its effects by
      activating specific receptors belonging to the GPCR family in target cells.
      Activation of histamine receptor can activate MAP kinases as recorded by
      monitoring the phosphorylation of extracellular signal regulated kinase (ERK).
      Despite this, ERK phosphorylation does not translate into pro-proliferative
      changes after histamine stimulation in HeLa cells. Here we show that histamine H1
      receptor activation mediates MAPK activation through PLCbeta, Src, PKCdelta and
      MEK pathway, but does not lead to nuclear relocalization of phospho-ERK (pERK),
      classically associated with pro-proliferative changes. Live cell imaging, FRET
      and FRAP measurements along with functional analysis reveal that pERK generated
      by histamine activation is physically and functionally restricted in the cytosol
      and the findings report a spatial regulation of MAPK cascade activated non
      canonically through GPCRs unlike its canonical activation by EGF.

PMID- 27871652
TI  - Epidemiology and Diagnosis of Anterior Cruciate Ligament Injuries.
AB  - Anterior cruciate ligament (ACL) injuries are increasingly common in the United
      States. This may be related to the increase in high school sports participation,
      particularly in female athletes. A significant proportion of these injuries are
      caused by noncontact mechanisms. The incidence of these noncontact injuries may
      be significantly reduced by enrolling young athletes in jump-training programs.
      The diagnosis of ACL injuries involves a focused history and physical
      examination, which can provide a high index of suspicion. Although radiographs
      are important to rule out associated injuries, the gold standard for diagnosis of
      ACL injuries is MRI, which has shown excellent accuracy.

PMID- 27871653
TI  - Surgical Management and Treatment of the Anterior Cruciate
      Ligament/Posterolateral Corner Injured Knee.
AB  - Posterolateral knee injuries occur more commonly than in the past. These injuries
      most commonly occur concurrent with cruciate ligament tears. The main stabilizers
      of the posterolateral knee are the fibular collateral ligament, the popliteus
      tendon, and the popliteofibular ligament. These static stabilizers function to
      prevent increased varus, external rotation, and coupled posterolateral rotation
      of the knee. The most important clinical tests to diagnose posterolateral knee
      injuries are the varus stress test, posterolateral drawer, and dial tests. Varus
      stress radiographs are key objective means to diagnose these injuries. Anatomic-
      based reconstructions have been validated to restore stability and improve
      outcomes.

PMID- 27871654
TI  - Surgical Management and Treatment of the Anterior Cruciate Ligament-Deficient
      Knee with Malalignment.
AB  - Varus malalignment and an increased tibial slope can result in instability in an
      anterior cruciate ligament (ACL)-deficient knee. Malalignment can also be a cause
      of recurrent instability following ACL reconstruction. Varus malalignment can
      contribute to loosening or failure of primary ACL reconstruction and contribute
      to progressive medial compartment arthritis. High tibial osteotomies performed in
      conjunction with ACL reconstruction can improve alignment, restore anterior knee
      stability, and help reduce the advancement of arthritis.

PMID- 27871655
TI  - Surgical Indications and Technique for Anterior Cruciate Ligament Reconstruction
      Combined with Lateral Extra-articular Tenodesis or Anterolateral Ligament
      Reconstruction.
AB  - After anterior cruciate ligament (ACL) rupture, anteroposterior and rotational
      laxity in the knee causes instability, functional symptoms, and damage to other
      intra-articular structures. Surgical reconstruction aims to restore the stability
      in the knee, and to improve function and ability to participate in sports. It
      also protects cartilage and menisci from secondary injuries. Because of
      persistent rotational instability after ACL reconstruction, combined intra
      articular and extra-articular procedures are more commonly performed. In this
      article, an overview of anatomy, biomechanical studies, current gold standard
      procedures, techniques, and research topics are summarized.

PMID- 27871656
TI  - Etiologic Factors That Lead to Failure After Primary Anterior Cruciate Ligament
      Surgery.
AB  - Anterior cruciate ligament (ACL) reconstruction is common in the active young
      population. Failure of ACL reconstruction can be due to continued or recurrent
      instability, stiffness, or patient-reported failure in the setting of seemingly
      successful surgical reconstruction, such as pain that limits activity. Multiple
      preoperative, intraoperative, and postoperative variables can be optimized to
      give the greatest likelihood of success. Some of these include timing of surgery,
      identification, and treatment of associated ligamentous, meniscal and chondral
      injuries, tunnel placement, graft choice, fixation, tensioning, and postoperative
      rehabilitation. This article reviews common causes of ACL reconstruction failure
      concentrating on modifiable factors.

PMID- 27871657
TI  - Surgical Pearls in Revision Anterior Cruciate Ligament Surgery: When Must I
      Stage?
AB  - Failed anterior cruciate ligament (ACL) reconstruction is a challenging clinical
      entity and revision ACL reconstruction is a technically challenging procedure.
      This article reviews the etiology of ACL failures, the need for appropriate
      examination and imaging studies, and discusses the technical considerations to
      allow for a successful revision reconstruction. Furthermore, we elaborate on the
      decision-making process of when a 2-stage revision is preferred to a single-stage
      revision.

PMID- 27871658
TI  - Rehabilitation Principles of the Anterior Cruciate Ligament Reconstructed Knee:
      Twelve Steps for Successful Progression and Return to Play.
AB  - The rehabilitation process begins immediately after injury to the anterior
      cruciate ligament (ACL). The goal of preoperative rehabilitation is to prepare
      the patient for surgery. Current rehabilitation programs focus on strengthening
      exercises and proprioceptive and neuromuscular control drills to provide a
      neurologic stimulus. It is also important to address preexisting factors,
      especially for the female athlete, that may predispose to future injury, such as
      hip and hamstring weakness. Our goal in the rehabilitation program is to restore
      full, unrestricted function and to assist the patient to return to 100% of the
      preinjury level while achieving excellent long-term outcomes.

PMID- 27871660
TI  - Management of the Anterior Cruciate Ligament-Injured Knee in the Skeletally
      Immature Athlete.
AB  - Intrasubstance tears of the anterior cruciate ligament (ACL) are being diagnosed
      with increasing frequency in the skeletally immature. Management options include
      nonoperative/ early surgical, or delayed surgical reconstruction.
      Nonoperative/delayed reconstruction results in worse functional outcomes than
      early reconstruction. Physicians are faced with a treatment dilemma; clinical and
      basic science studies have demonstrated risk of limb-length discrepancy and
      angular deformity with ACL reconstruction. Vertical drill tunnels decrease
      physeal damage and minimize growth deformity; however, this technique results in
      nonanatomic ACL graft placement. All-epiphyseal reconstruction avoids damage to
      the growth plate. These techniques are biomechanically superior to extraarticular
      and modified physeal-sparing procedures.

PMID- 27871659
TI  - Graft Selection in Anterior Cruciate Ligament Surgery: Who gets What and Why?
AB  - Anterior cruciate ligament (ACL) injuries are common and affect a young, active
      patient population. Despite much research, ACL reconstruction graft choice
      remains a topic of debate. Based on the best available evidence, autograft seems
      to be superior to allograft for ACL reconstruction in young, active patients.
      Future high-level studies are required in order to better define the role of
      allograft in ACL reconstruction. As graft choice is often influenced by surgeon
      preference, it is important that surgeons understand the current literature as
      well as the goals of their patients.

PMID- 27871661
TI  - Single-Bundle Anatomic Anterior Cruciate Ligament Reconstruction: Surgical
      Technique Pearls and Pitfalls.
AB  - Anterior cruciate ligament (ACL) ruptures are some of the most common sports
      related injuries. Treatment of these injuries with ACL reconstruction has evolved
      over the last several decades. Anatomic single-bundle ACL reconstruction offers
      an accurate and reproducible method to reproduce native knee anatomy, restore
      knee kinematics, and ultimately restore function and decrease long-term
      degenerative effects. The importance of adequate arthroscopic visualization and a
      thorough understanding of the native anatomic ACL landmarks are discussed in this
      article. Furthermore, surgical technique, pearls, pitfalls, potential
      complications, rehabilitation, and outcomes are reviewed.

PMID- 27871662
TI  - Indications for Two-Incision (Outside-In) Anterior Cruciate Ligament
      Reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction is a commonly performed
      procedure. Drilling the femoral tunnel independent of the tibial tunnel has
      become popular as surgeons strive to create tunnels in the anatomic locations of
      the femoral and tibial attachments of the native ligament. The 2-incision
      technique effectively and reproducibly accomplishes this goal. The 2-incision
      technique for ACL reconstruction is a valuable tool in the skillset of the
      reconstructive knee surgeon. Indications for the 2-incision surgery are reviewed
      in detail. Furthermore, technical tips, complications, and outcomes are
      discussed.

PMID- 27871663
TI  - Surgical Management and Treatment of the Anterior Cruciate Ligament/Medial
      Collateral Ligament Injured Knee.
AB  - The medial collateral ligament (MCL) is the most commonly injured ligament of the
      knee. The anterior cruciate ligament (ACL) is the most commonly injured ligament
      in conjunction with the MCL. Most MCL injuries can be treated nonoperatively,
      whereas the ACL often requires reconstruction. A good physical examination is
      essential for diagnosis, whereas radiographs and MRI of the knee confirm
      diagnosis and help guide treatment planning. Preoperative physical therapy should
      be completed before surgical management to allow for return of knee range of
      motion and an attempt at MCL healing.

PMID- 27871664
TI  - Gross, Arthroscopic, and Radiographic Anatomies of the Anterior Cruciate
      Ligament: Foundations for Anterior Cruciate Ligament Surgery.
AB  - The anterior cruciate ligament (ACL) is one of the more studied structures in the
      knee joint. It is not a tubular structure, but is much narrower in its
      midsubstance and broader at its ends, producing an hourglass shape. The ACL is
      composed of 2 functional bundles, the anteromedial and posterolateral bundles,
      that are named for their location of insertion on the anterior surface of the
      tibial plateau. Although the relative contribution in terms of total cross
      sectional area of the ACL has been noted to be equal in regards to each bundle,
      dynamically these bundles demonstrate different properties for knee function.

PMID- 27871665
TI  - Anterior Cruciate Ligament.

PMID- 27871666
TI  - Management of the Anterior Cruciate Ligament Deficient Knee.

PMID- 27871667
TI  - Transport of soil-aged silver nanoparticles in unsaturated sand.
AB  - Engineered nanoparticles released into soils may be coated with humic substances,
      potentially modifying their surface properties. Due to their amphiphilic nature,
      humic coating is expected to affect interaction of nanoparticle at the air-water
      interface. In this study, we explored the roles of the air-water interface and
      solid-water interface as potential sites for nanoparticle attachment and the
      importance of hydrophobic interactions for nanoparticle attachment at the air
      water interface. By exposing Ag nanoparticles to soil solution extracted from the
      upper soil horizon of a floodplain soil, the mobility of the resulting "soil
      aged" Ag nanoparticles was investigated and compared with the mobility of citrate
      coated Ag nanoparticles as investigated in an earlier study. The mobility was
      determined as a function of hydrologic conditions and solution chemistry using
      column breakthrough curves and numerical modeling. Specifically, we compared the
      mobility of both types of nanoparticles for different unsaturated flow conditions
      and for pH=5 and pH=9. The soil-aged Ag NP were less mobile at pH=5 than at pH=9
      due to lower electrostatic repulsion at pH=5 for both types of interfaces.
      Moreover, the physical flow field at different water contents modified the impact
      of chemical forces at the solid-water interface. An extended Derjaguin-Landau
      Verwey-Overbeek (eDLVO) model did not provide satisfactory explanation of the
      observed transport phenomena unlike for the citrate-coated case. For instance,
      the eDLVO model assuming sphere-plate geometry predicts a high energy barrier
      (>90 kT) for the solid-water interface, indicating that nanoparticle attachment
      is less likely. Furthermore, retardation through reversible sorption at the air
      water interface was probably less relevant for soil-aged nanoparticles than for
      citrate-coated nanoparticles. An additional cation bridging mechanism and
      straining within the flow field may have enhanced nanoparticle retention at the
      solid-water interface. The results indicate that the mobility of engineered Ag
      nanoparticles is sensitive to solution chemistry, especially pH and the
      concentration of multivalent cations, and to the unsaturated flow conditions
      influencing particle interaction at biogeochemical interfaces.

PMID- 27871668
TI  - Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression.
AB  - The ventral striatum (nucleus accumbens) and its role in mood, reward, and
      motivation has been the focus of significant research. Despite this interest,
      little work has addressed cell type-specific distinctions in medium spiny neurons
      (MSNs), the main projection neurons in the nucleus accumbens and dorsal striatum,
      and their function in relation to stress and depression. Previous work has shown
      opposing roles for D1 and D2 receptor MSN subtypes in depression-like outcomes to
      stress, particularly in regard to repeated neuronal stimulation and excitatory
      transmission. Yet the mechanisms of action are still unknown. We discuss
      potential mechanisms by which MSN subtype function promotes dichotomous
      behavioral outcomes caused by differences in cellular plasticity, subcellular
      signaling pathways, and genetic expression. This review aims to address our
      current understanding about the role of nucleus accumbens MSN subtypes in stress
      related depression behavior and speculates on how currently understood mechanisms
      contribute to factors that control the activity of MSNs.

PMID- 27871669
TI  - Induction and Blockade of Adolescent Cocaine-Induced Habits.
AB  - BACKGROUND: Cocaine use during adolescence increases vulnerability to drug
      dependence and decreases the likelihood that individuals will seek treatment as
      adults. Understanding how early-life cocaine exposure influences decision-making
      processes in adulthood is thus critically important. METHODS: Adolescent or adult
      mice were exposed to subchronic cocaine, then behavioral sensitivity to changes
      in the predictive relationship between actions and their consequences was tested.
      Dendritic spines on the principal pyramidal neurons of the orbitofrontal
      prefrontal cortex (oPFC) were also imaged and enumerated. To determine whether
      cytoskeletal regulatory systems in the oPFC influenced decision-making
      strategies, we then inhibited the activity of Abl family and Rho kinases as well
      as NR2B-containing N-methyl-D-aspartate receptors. We also attempted to block the
      reinstatement of cocaine seeking in cocaine self-administering mice. RESULTS:
      Adult mice with a history of subchronic cocaine exposure in adolescence engaged
      habit-based response strategies at the expense of goal-directed decision-making
      strategies and had fewer dendritic spines in the oPFC. Inhibition of the
      cytoskeletal regulatory Abl family kinases in the oPFC recapitulated these
      neurobehavioral deficiencies, whereas Rho kinase inhibition corrected response
      strategies. Additionally, the NR2B-selective N-methyl-D-aspartate receptor
      antagonists ifenprodil and CP-101,606 blocked cocaine-induced habits; this was
      dependent on Abl family signaling in the oPFC. Ifenprodil also mitigated cue
      induced reinstatement of cocaine seeking in mice self-administering cocaine.
      CONCLUSIONS: We suggest that adolescent cocaine exposure confers a bias toward
      habit-based behavior in adulthood via long-term cellular structural modifications
      in the oPFC. Treatments aimed at mitigating the durable consequences of early
      life cocaine use may benefit from targeting cytoskeletal regulatory systems.

PMID- 27871672
TI  - How Species Boundaries Are Determined: A Response to Alexander et al.

PMID- 27871670
TI  - Convergence of Sex Differences and the Neuroimmune System in Autism Spectrum
      Disorder.
AB  - The male bias in autism spectrum disorder incidence is among the most extreme of
      all neuropsychiatric disorders, yet the origins of the sex difference remain
      obscure. Developmentally, males are exposed to high levels of testosterone and
      its byproduct, estradiol. Together these steroids modify the course of brain
      development by altering neurogenesis, cell death, migration, differentiation,
      dendritic and axonal growth, synaptogenesis, and synaptic pruning, all of which
      can be deleteriously impacted during the course of developmental neuropsychiatric
      disorders. Elucidating the cellular mechanisms by which steroids modulate brain
      development provides valuable insights into how these processes may go awry. An
      emerging theme is the role of inflammatory signaling molecules and the innate
      immune system in directing brain masculinization, the evidence for which we
      review here. Evidence is also emerging that the neuroimmune system is
      overactivated in individuals with autism spectrum disorder. These combined
      observations lead us to propose that the natural process of brain masculinization
      puts males at risk by moving them closer to a vulnerability threshold that could
      more easily be breached by inflammation during critical periods of brain
      development. Two brain regions are highlighted: the preoptic area and the
      cerebellum. Both are developmentally regulated by the inflammatory prostaglandin
      E2, but in different ways. Microglia, innate immune cells of the brain, and
      astrocytes are also critical contributors to masculinization and illustrate the
      importance of nonneuronal cells to the health of the developing brain.

PMID- 27871673
TI  - Is It Time for Synthetic Biodiversity Conservation?
AB  - Evidence indicates that, despite some critical successes, current conservation
      approaches are not slowing the overall rate of biodiversity loss. The field of
      synthetic biology, which is capable of altering natural genomes with extremely
      precise editing, might offer the potential to resolve some intractable
      conservation problems (e.g., invasive species or pathogens). However, it is our
      opinion that there has been insufficient engagement by the conservation community
      with practitioners of synthetic biology. We contend that rapid, large-scale
      engagement of these two communities is urgently needed to avoid unintended and
      deleterious ecological consequences. To this point we describe case studies where
      synthetic biology is currently being applied to conservation, and we highlight
      the benefits to conservation biologists from engaging with this emerging
      technology.

PMID- 27871674
TI  - The White-Knight Hypothesis, or Does the Environment Limit Innovations?
AB  - Organisms often harbor latent traits that are byproducts of other adaptations.
      Such latent traits are not themselves adaptive but can become adaptive in the
      right environment. Here I discuss several examples of such traits. Their
      abundance suggests that environmental change rather than new mutations might
      often limit the origin of evolutionary adaptations and innovations. This is
      important, because environments can change much faster than new mutations arise.
      I introduce a conceptual model that distinguishes between mutation-limited and
      environment-limited trait origins and suggest how experiments could help
      discriminate between them. Wherever latent traits are plentiful, ecology rather
      than genetics might determine how fast new adaptations originate and thus how
      fast adaptive Darwinian evolution proceeds.

PMID- 27871675
TI  - Glucagon-like Peptide-1 and the Central/Peripheral Nervous System: Crosstalk in
      Diabetes.
AB  - Glucagon-like peptide-1 (GLP-1) is released in response to meals and exerts
      important roles in the maintenance of normal glucose homeostasis. GLP-1 is also
      important in the regulation of neurologic and cognitive functions. These actions
      are mediated via neurons in the nucleus of the solitary tract that project to
      multiple regions expressing GLP-1 receptors (GLP-1Rs). Treatment with GLP-1R
      agonists (GLP-1-RAs) reduces ischemia-induced hyperactivity, oxidative stress,
      neuronal damage and apoptosis, cerebral infarct volume, and neurologic damage,
      after cerebral ischemia, in experimental models. Ongoing human trials report a
      neuroprotective effect of GLP-1-RAs in Alzheimer's and Parkinson's disease. In
      this review, we discuss the role of GLP-1 and GLP-1-RAs in the nervous system
      with focus on GLP-1 actions on appetite regulation, glucose homeostasis, and
      neuroprotection.

PMID- 27871671
TI  - Tumor control probability modeling for stereotactic body radiation therapy of
      early-stage lung cancer using multiple bio-physical models.
AB  - This work is to analyze pooled clinical data using different radiobiological
      models and to understand the relationship between biologically effective dose
      (BED) and tumor control probability (TCP) for stereotactic body radiotherapy
      (SBRT) of early-stage non-small cell lung cancer (NSCLC). The clinical data of 1
      , 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP from 46 selected studies were
      collected for SBRT of NSCLC in the literature. The TCP data were separated for
      Stage T1 and T2 tumors if possible, otherwise collected for combined stages. BED
      was calculated at isocenters using six radiobiological models. For each model,
      the independent model parameters were determined from a fit to the TCP data using
      the least chi-square (chi2) method with either one set of parameters regardless
      of tumor stages or two sets for T1 and T2 tumors separately. The fits to the
      clinic data yield consistent results of large alpha/beta ratios of about 20Gy for
      all models investigated. The regrowth model that accounts for the tumor
      repopulation and heterogeneity leads to a better fit to the data, compared to
      other 5 models where the fits were indistinguishable between the models. The
      models based on the fitting parameters predict that the T2 tumors require about
      additional 1Gy physical dose at isocenters per fraction (?5 fractions) to achieve
      the optimal TCP when compared to the T1 tumors. In conclusion, this systematic
      analysis of a large set of published clinical data using different
      radiobiological models shows that local TCP for SBRT of early-stage NSCLC has
      strong dependence on BED with large alpha/beta ratios of about 20Gy. The six
      models predict that a BED (calculated with alpha/beta of 20) of 90Gy is
      sufficient to achieve TCP?95%. Among the models considered, the regrowth model
      leads to a better fit to the clinical data.

PMID- 27871677
TI  - IMPETUS - Interactive MultiPhysics Environment for Unified Simulations.
AB  - We introduce IMPETUS - Interactive MultiPhysics Environment for Unified
      Simulations, an object oriented, easy-to-use, high performance, C++ program for
      three-dimensional simulations of complex physical systems that can benefit a
      large variety of research areas, especially in cell mechanics. The program
      implements cross-communication between locally interacting particles and
      continuum models residing in the same physical space while a network facilitates
      long-range particle interactions. Message Passing Interface is used for inter
      processor communication for all simulations.

PMID- 27871676
TI  - Streamline crossing: An essential mechanism for aerosol dispersion in the
      pulmonary acinus.
AB  - The dispersion of inhaled microparticles in the pulmonary acinus of the lungs is
      often attributed to the complex interplay between convective mixing, due to
      irreversible flows, and intrinsic particle motion (i.e. gravity and diffusion).
      However, the role of each mechanism, the exact nature of such interplay between
      them and their relative importance still remain unclear. To gain insight into
      these dispersive mechanisms, we track liquid-suspended microparticles and extract
      their effective diffusivities inside an anatomically-inspired microfluidic acinar
      model. Such results are then compared to experiments and numerical simulations in
      a straight channel. While alveoli of the proximal acinar generations exhibit
      convective mixing characteristics that lead to irreversible particle
      trajectories, this local effect is overshadowed by a more dominant dispersion
      mechanism across the ductal branching network that arises from small but
      significant streamline crossing due to intrinsic diffusional motion in the
      presence of high velocity gradients. We anticipate that for true airborne
      particles, which exhibit much higher intrinsic motion, streamline crossing would
      be even more significant.

PMID- 27871678
TI  - Direct numerical simulation of expiratory crackles: Relationship between airway
      closure dynamics and acoustic fluctuations.
AB  - This paper investigates the relationship between airway closure dynamics and
      acoustic fluctuations in expiratory crackles using direct numerical simulation. A
      unified mathematical model is proposed to deal with flow in an airway, elastic
      deformation of the airway wall, surface tension driven motion of the liquid film
      that lines the airway, and their acoustic fluctuations because of material
      compressibility. Airway closure is induced by increasing the surrounding
      pressure, then the source of the pressure fluctuations is measured over time. Our
      results show that the airway closure occurs suddenly because of a bridge
      formation of the liquid film, and high energy transfer occurs between the kinetic
      energy, the surface energy of the liquid interface, and the elastic energy of the
      airway wall, invoking a large acoustic fluctuation that causes the expiratory
      crackles. Nonlinear behavior is observed in terms of the airway wall stiffness;
      the dynamic motion of the airway closure becomes moderate and both the energy
      transfer and acoustic fluctuations are dramatically reduced with an increase in
      airway wall stiffness.

PMID- 27871679
TI  - Discharge criteria after colon resection: Is return of bowel function necessary?
AB  - BACKGROUND: This study was performed to evaluate tolerance of liquids as
      discharge criteria in a perioperative enhanced recovery protocol. METHODS:
      Patients undergoing elective colon resections were prospectively enrolled in a
      standardized perioperative enhanced recovery process. Patients were eligible for
      discharge when able to tolerate sufficient oral liquids, as determined by
      clinical means, that intravenous fluids were no longer needed. RESULTS: Over an
      18 month period, 94 patients were evaluated; 75 (80%) tolerated sufficient
      liquids such that intravenous fluids were no longer needed by the second and all
      by the third postoperative day. The average postoperative length of stay was 3.8
      days. At discharge, 59 (63%) and 20 (21%) patients reported passage of flatus and
      stool respectively. On 30 day follow up, 8 (8.5%) patients had been re-admitted.
      CONCLUSION: These data suggest that after elective colon surgery, patients can be
      discharged when able to tolerate sufficient oral liquids.

PMID- 27871680
TI  - Clinical significance of circumportal pancreas, a rare congenital anomaly, in
      pancreatectomy.
AB  - BACKGROUND: Circumportal pancreas is a rare congenital pancreatic anomaly. The
      aim of this study was to clarify the clinical characteristics of patients with
      circumportal pancreases undergoing pancreatectomy. METHODS: The medical records
      of 508 patients who underwent pancreatectomy were retrospectively reviewed. The
      prevalence of circumportal pancreas and related anatomical variations were
      assessed. Surgical procedures and postoperative outcomes were compared in
      patients with and without circumportal pancreas. RESULTS: Circumportal pancreas
      was observed in 9 of the 508 patients (1.7%). In all nine patients, the portal
      vein was completely encircled by the pancreatic parenchyma above the level of the
      splenoportal junction, and the main pancreatic duct ran dorsal to the portal
      vein. The rate of variant hepatic artery did not differ significantly in patients
      with and without circumportal pancreas. Pancreatic fistula developed more
      frequently in patients with than without circumportal pancreas (44% vs. 14%, p =
      0.03), but other clinical parameters did not differ significantly in these two
      groups. CONCLUSIONS: Despite being rare, circumportal pancreas may increase the
      risk of postoperative pancreatic fistula in patients undergoing pancreatectomy.
      However, a prospective, large-cohort study is necessary to determine the real
      incidence of relevant anatomical variations and the definitive clinical
      significance of this rare anomaly.

PMID- 27871681
TI  - Postoperative antibiotic use and the incidence of intra-abdominal abscess in the
      setting of suppurative appendicitis: a retrospective analysis.
AB  - BACKGROUND: Although guidelines exist for postoperative antibiotic use in acute
      appendicitis that is perforated, gangrenous, or simple/uncomplicated, there are
      less data about its use in suppurative appendicitis. Here, we targeted this
      subgroup of patients to determine whether postoperative antibiotic administration
      affects incidence of intra-abdominal abscess formation. METHODS: We
      retrospectively examined 1,192 patients who underwent laparoscopic appendectomy
      for acute appendicitis at Kaiser Permanente Fontana Hospital between August 2010
      and August 2013. Suppurative appendicitis was described for 143 (12%) patients.
      Fifty-two patients received postoperative antibiotics for at least 1 week on
      discharge home, 91 did not. RESULTS: Of 143 patients with suppurative
      appendicitis, 1 (1.9%) who received postoperative antibiotics came back with an
      intra-abdominal abscess within 1 month. Of the 91 patients in the no antibiotic
      group, 1 (1.1%) came back with an intra-abdominal abscess. CONCLUSIONS: The
      administration of postoperative antibiotic in the setting of suppurative
      appendicitis has no effect on the rate of intra-abdominal abscess formation.
      Routine postoperative antibiotics may not be necessary in this patient
      population, and more evidence is needed to justify its use.

PMID- 27871682
TI  - Factors affecting mortality after penetrating cardiac injuries: 10-year
      experience at urban level I trauma center.
AB  - BACKGROUND: Despite the lethality of injuries to the heart, optimizing factors
      that impact mortality for victims that do survive to reach the hospital is
      critical. METHODS: From 2003 to 2012, prehospital data, injury characteristics,
      and clinical patient factors were analyzed for victims with penetrating cardiac
      injuries (PCIs) at an urban, level I trauma center. RESULTS: Over the 10-year
      study, 80 PCI patients survived to reach the hospital. Of the 21 factors
      analyzed, prehospital cardiopulmonary resuscitation (odds ratio [OR] = 30), scene
      time greater than 10 minutes (OR = 58), resuscitative thoracotomy (OR = 19), and
      massive left hemothorax (OR = 15) had the greatest impact on mortality. Cardiac
      tamponade physiology demonstrated a "protective" effect for survivors to the
      hospital (OR = .08). CONCLUSIONS: Trauma surgeons can improve mortality after PCI
      by minimizing time to the operating room for early control of hemorrhage. In PCI
      patients, tamponade may provide a physiologic advantage (lower mortality)
      compared to exsanguination.

PMID- 27871683
TI  - Perioperative support, not volume, is necessary to optimize outcomes in surgical
      management of necrotizing enterocolitis.
AB  - BACKGROUND: This study examines the relationship between hospital volume of
      surgical cases for necrotizing enterocolitis (NEC) and patient outcomes. METHODS:
      A retrospective cross-sectional review was performed using the HCUP SID for
      California from 2007 to 2011. Patients with NEC who underwent surgery were
      identified using ICD-9CM codes. Risk-adjusted models were constructed with mixed
      effects logistic regression using patient and demographic covariates. RESULTS: 23
      hospitals with 618 patients undergoing NEC-related surgical intervention were
      included. Overall mortality rate was 22.5%. There were no significant differences
      in the number of NICU beds (p = 0.135) or NICU intensivists (p = 0.469) between
      high and low volume hospitals. Following risk adjustment, no difference in
      mortality rate was observed between high and low volume hospitals respectively
      (24.0% vs. 20.3%, p = 0.555). CONCLUSIONS: Our observation that neonates with NEC
      treated at low-volume centers have no increased risk of mortality may be
      explained by similar availability of NICU and intensivists resources across
      hospitals.

PMID- 27871684
TI  - The utility of 5-aminolevulinic acid-mediated photodynamic diagnosis in the
      detection of intraoperative bile leakage.
AB  - PURPOSE: The purpose of this retrospective study was to evaluate the utility of
      the new intraoperative bile leakage test as a preventive measure of postoperative
      bile leakage. METHOD: 737 patients were retrospectively analyzed with respect to
      the management of intra- and post-operative bile leakage. RESULTS: Nine (8.3%) of
      109 patients evaluated using conventional white light fluorescent imaging were
      recognized as having intra-operative bile leakage. However, performance of 5
      aminolevulinic acid (5-ALA)-mediated PDD detected bile leakage intraoperatively
      not only in these 9 patients, but also in an additional 6 patients, such that
      'red fluorescence' at the cut surface of the liver, was visualized in a total of
      15 patients. The postoperative courses of most patients were uneventful, and
      postoperative bile leakages occurred in only one (0.9%) patient. CONCLUSION: 5
      ALA fluorescence imaging may be needed to prevent postoperative bile leakage in
      patients at high risk for this surgical complication after hepatic resection.

PMID- 27871686
TI  - Eliminating the organ transplant waiting list: The future with perfusion
      decellularized organs.

PMID- 27871685
TI  - Comparison of ultrasound frequency in laryngeal ultrasound for vocal cord
      evaluation.
AB  - BACKGROUND: Laryngeal ultrasound is a new method of vocal cord evaluation in
      patients at risk for vocal cord palsy. However, the previously described
      laryngeal ultrasound reportedly has a high failure rate of vocal cord
      visualization in male patients. We compared 2 ultrasound frequencies in laryngeal
      ultrasound to improve on the limitations of this method. METHOD: A total of 301
      (55 male, 246 female) consecutive laryngeal ultrasound and direct laryngoscopy
      exams were performed for patients with thyroidectomy and other neck operations.
      High-frequency transducer (12-5 MHz broad band spectrum) and low-frequency
      transducer (9-3 MHz broad band spectrum) were used for all laryngeal ultrasound.
      Findings were independently cross-validated with direct laryngoscopy. RESULTS:
      High-frequency and low-frequency laryngeal ultrasound had 88.4% and 97.7%
      visualization rates, respectively. In addition, low-frequency laryngeal
      ultrasound showed improved sensitivity of 97.6% and specificity of 96.5%,
      compared with a sensitivity of 92.9% and specificity of 86.5% for high-frequency
      laryngeal ultrasound in vocal cord evaluation. CONCLUSION: The low-frequency
      laryngeal ultrasound method significantly enhances the visualization of vocal
      cords, especially in patients who have diffuse thyroid cartilage calcification
      interrupting laryngeal ultrasound, and therefore enhances the overall efficacy of
      laryngeal ultrasound as a perioperative diagnostic tool for vocal cord palsy.
      Hence, we recommend using a low-frequency transducer (about 9-3 MHz) for
      laryngeal ultrasound if it is available.

PMID- 27871687
TI  - Portal vein aneurysm incidentaloma.

PMID- 27871688
TI  - An Unusual Cause of a Scalp Mass.

PMID- 27871689
TI  - Reply.

PMID- 27871691
TI  - Lucy fell from a tree and plunged 40 feet to her death.

PMID- 27871690
TI  - The Relation between Breast Milk Sodium to Potassium Ratio and Maternal Report of
      a Milk Supply Concern.
AB  - We report that, among exclusively breastfeeding mothers at day 7 postpartum,
      those with milk supply concerns were significantly more likely to exhibit
      biochemical evidence of less progress toward mature lactation (elevated ratio of
      breast milk sodium to potassium concentration). Furthermore, an elevated ratio of
      breast milk sodium to potassium concentration was predictive of early weaning.

PMID- 27871692
TI  - Authors' response.

PMID- 27871693
TI  - Adverse effects of lingual and buccal orthodontic techniques.

PMID- 27871694
TI  - Authors response.

PMID- 27871695
TI  - Herbst appliance anchored to miniscrews with 2 types of ligation.

PMID- 27871696
TI  - Do what I say and not what you do.

PMID- 27871698
TI  - Your discretion, please.

PMID- 27871699
TI  - Evaluation of enamel demineralization in adolescents after rapid maxillary
      expansion using the quantitative light-induced fluorescence method: A single
      center, randomized controlled clinical trial.
AB  - INTRODUCTION: The aim of this 2-arm parallel trial was to evaluate enamel
      demineralization after rapid maxillary expansion (RME) compared with an untreated
      control group using quantitative light-induced fluorescence. METHODS: Thirty-six
      patients who needed RME as part of their orthodontic treatment were separated
      randomly into either the control group or the intervention group (RME).
      Eligibility criteria included crossbite, no previous orthodontic treatment, no
      systemic disease, and all permanent teeth erupted except second and third molars.
      The main outcome was quantitative evaluation of demineralization, and assessment
      of the vulnerability of each tooth to demineralization was the secondary outcome.
      Randomization was made at the start of the study with preprepared random number
      tables. Blinding was applicable for outcome assessment only. Patients in the RME
      group underwent expansion with a bonded acrylic expander; patients in the control
      group were untreated. Records were taken using quantitative light-induced
      fluorescence Digital Biluminator (Inspektor Research Systems, Amsterdam, The
      Netherlands) in pretreatment and posttreatment observation phases. The presence
      and extent of lesions on the buccal surfaces of all teeth, except the second and
      third molars, were assessed. The fluorescence loss, lesion area, and percentage
      of fluorescence loss were determined using the system's software. The numbers of
      teeth with more than a 5% change in fluorescence loss, were calculated. Data were
      analyzed with Wilcoxon signed rank, Mann-Whitney U, multivariate analysis of
      variance, and chi-square tests (P <0.05). Risk and odds ratios were calculated.
      RESULTS: A total of 36 patients were randomized to either the RME or the control
      group in a 1:1 ratio. This study was completed with 18 patients in the RME group
      (8 girls, 10 boys; mean age, 14.2 +/- 1.0 years) and 18 patients in the control
      group (10 girls, 8 boys; mean age: 14.1 +/- 0.8 years). All patients completed
      the study, and none were lost to follow-up. The area of demineralization
      decreased in the RME group (-17.50 mm2), which was a significantly greater
      decrease than in the control group (0.00) (effect size, -2.63; mean difference, 
      87.94; 95% confidence interval, -223.75-47.86; P = 0.008). No statistically
      significant difference was found for fluorescence loss. The numbers of teeth with
      demineralization and remineralization were higher in the treatment group.
      According to the risk ratio, the difference between groups regarding
      demineralization was not significant. No harm was found except gingivitis
      associated with the bonded appliance. CONCLUSIONS: RME therapy using a bonded
      expander does not increase enamel demineralization. REGISTRATION: This trial was
      not registered. PROTOCOL: The protocol was not published before trial
      commencement.

PMID- 27871700
TI  - Laypeople's perceptions of frontal smile esthetics: A systematic review.
AB  - INTRODUCTION: The emphasis on dental esthetics has increased in recent years.
      There are, however, differences in esthetic perceptions among professional and
      lay groups. The aim of this comprehensive review was to update previous reviews
      and answer the following research question: Can lay thresholds for acceptance of
      smile esthetic anomalies be defined? METHODS: A systematic search in the medical
      literature (PubMed, PMC, NLM, Embase, Cochrane Central Register of Controlled
      Clinical trials, Web of Knowledge, Scopus, Google Scholar, and LILACs) was
      performed to identify all peer-reviewed articles reporting data regarding
      evaluations of laypeople's perceptions of dental esthetic factors. RESULTS: Of
      the 6032 analyzed articles, 66 studies were selected for the final review
      process. Among the selected articles investigated perceptions of diastema, 15
      analyzed modifications in tooth size and shape, 8 considered incisor positions,
      15 evaluated midline discrepancies, 16 investigated buccal corridors, 26 analyzed
      gingival display and design, 3 considered lip height, and 20 investigated
      miscellaneous factors. Threshold values were identified for the following
      features: diastema (0-2 mm), tooth size and shape of incisor position, midline
      discrepancy (0-3 mm), buccal corridors (5-16 mm), gingival exposure (1.5-4 mm),
      occlusal canting (0 degrees -4 degrees ), and overbite (2-5 mm). Furthermore, few
      other smile characteristics were found to be significantly associated with
      perception of smile aesthetics, even though any threshold could be detected.
      CONCLUSIONS: On the basis of the obtained results, threshold values for the main
      features of smile and dental esthetics could be identified. Limitations of the
      present study were the heterogeneity of data which made it impossible to perform
      a meta-analysis, and the lack of information about sample selection and selective
      outcome reporting.

PMID- 27871701
TI  - Comparative evaluation of 2 skeletally anchored maxillary protraction protocols.
AB  - INTRODUCTION: The aim of this study was to evaluate and compare the effects of 2
      protocols of bone-anchored maxillary protraction with an untreated control group.
      METHODS: Thirty growing Class III subjects with maxillary deficiency in the late
      mixed or early permanent dentition were included in the study. In group 1 (n =
      10), skeletally anchored facemasks were used with miniplates placed at the
      zygomatic buttress. In group 2 (n = 10), the patients were treated with Class III
      elastics extending from infrazygomatic miniplates in the maxilla to symphyseal
      miniplates in the mandible. Group 3 (n = 10) was an untreated control group.
      Pretreatment and posttreatment cephalometric radiographs were analyzed. RESULTS:
      The treatment periods were 8 and 8.9 months in groups 1 and 2, respectively, and
      the untreated control group was observed for 9.4 months. The maxilla moved
      forward significantly in groups 1 and 2 compared with the untreated control group
      (4.87 mm in group 1, 5.81 mm in group 2); overjet and maxillary incisor display
      were improved without proclination or mesialization of the maxillary teeth
      relative to the maxillary base. Soft tissue harmony demonstrated the great
      improvement. However, group 1 showed more opening rotation of the mandible and
      lingual inclination of the mandibular incisors than did group 2. CONCLUSIONS: The
      2 skeletal anchorage protocols for maxillary protraction effectively resolved the
      severe maxillary deficiently in growing Class III patients. However, vertical
      changes and retroclination of the mandibular incisors were better controlled by
      Class III elastics extending from the infrazygomatic miniplates in the maxilla to
      the symphyseal miniplates in the mandible (group 2).

PMID- 27871702
TI  - Comparison of direct and indirect skeletal anchorage systems combined with 2
      canine retraction techniques.
AB  - INTRODUCTION: We compared the effectiveness of 2 canine retraction springs and
      anchorage systems (direct and indirect skeletal anchorage) in patients requiring
      first premolar extractions and maximum anchorage in the maxilla. METHODS: Thirty
      six patients were included (17 male, 19 female; mean age, 16.8 +/- 2.4 years). A
      mini-implant-supported Nance appliance with indirect skeletal anchorage system
      was used in 18 patients and a mini-implant-supported direct skeletal anchorage
      system in the remaining patients. In each patient, a segmental retraction arch
      with a reverse closing loop was applied to a maxillary canine, and a Ladanyi
      spring (Dentaurum, Ispringen, Germany) was applied to the other canine randomly
      after extraction of the maxillary first premolars. The retraction process was
      continued until a Class I canine relationship was obtained. Lateral cephalometric
      films and orthodontic casts taken before and after retraction in the
      distalization process were used to evaluate changes during canine distalization.
      The measurements were statistically evaluated using paired and independent t
      tests with 95% confidence intervals. RESULTS: The reverse closing loop and the
      Ladanyi spring were found to be effective in canine distalization (P <=0.001).
      There were no statistically significant differences between the reverse closing
      loop and the Ladanyi spring with regard to canine distalization rates (P >=0.05).
      Both systems were effective in providing maximum anchorage (P >=0.05); no
      statistically significant differences were detected in molar anchorage loss rates
      between the 2 methods (P >=0.05). CONCLUSIONS: These 2 systems can be used during
      segmental distalization of canines requiring maximum anchorage with no
      significant anchorage loss.

PMID- 27871703
TI  - Change in the vertical dimension of Class II Division 1 patients after use of
      cervical or high-pull headgear.
AB  - INTRODUCTION: The goals of this study were to compare the effects that cervical
      and high-pull headgear have on the vertical dimensions in Class II Division 1
      patients during phase 1 treatment and to compare these effects with untreated
      predicted growth for the sample population. METHODS: Pretreatment and
      posttreatment cephalometric radiographs of children who had undergone Class II
      Division 1 correction with cervical (n = 22) or high-pull headgear (n = 19) were
      analyzed for the measurements that describe the changes in the vertical component
      of growth and mandibular position. The groups were matched for age (mean, 9 +/-
      2.5 years), treatment time (mean, 14 months), malocclusion, and similar skeletal
      features. The groups were compared with each other and also with an untreated
      growth model. RESULTS: Treatment with cervical headgear resulted in smaller
      increases in measurements that describe the vertical dimension than with high
      pull headgear. Cervical headgear showed more favorable changes in mandibular
      growth that were statistically significant when compared with the untreated
      growth models. CONCLUSIONS: In this study, the cervical headgear showed more
      control over the vertical dimension and produced more favorable changes in
      mandibular position by normalizing the occlusal plane. Compared with the
      untreated growth model, cervical headgear worked synergistically with growth to
      produce more optimal changes in mandibular position.

PMID- 27871704
TI  - Accuracy and reliability of orthodontists using cone-beam computerized tomography
      for assessment of adenoid hypertrophy.
AB  - INTRODUCTION: Our objectives were to evaluate the reliability of agreement
      between orthodontists, with various degrees of cone-beam computed tomography
      (CBCT) imaging manipulation comfort, in classifying adenoid hypertrophy through
      CBCT generated images and also to determine how accurate orthodontists are
      compared with the gold standard diagnosis, nasopharyngoscopy. METHODS: This was a
      cross-sectional study in which a randomized list of board-certified orthodontists
      evaluated different degrees of adenoid hypertrophy of a stratified sampling of 10
      scans. The available pool of CBCT images was from a multidisciplinary airway
      clinic in which children and adolescents had a CBCT scan and a nasopharyngoscopy
      (reference standard) by an otolaryngologist (head and neck surgeon) on the same
      day. The participating orthodontists used the same viewer software and computer,
      and had access to a previously published visual guideline for evaluating adenoid
      size. RESULTS: Fourteen orthodontists evaluated 10 CBCT reconstructions.
      Interoperator reliability was excellent (intraclass correlation coefficient
      [ICC], 0.941; 95% confidence interval, 0.882-0.984). However, the orthodontists'
      evaluations against the reference standard demonstrated poor accuracy, (ICC mean,
      0.39; ICC range, 0.0-0.74). Dichotomous data representing healthy and unhealthy
      patients were analyzed individually, and the orthodontists' evaluations and the
      nasopharyngoscopy results (accuracy) showed, on average, poor kappa values (mean,
      0.44; range, 0.20-0.80). CONCLUSIONS: Different levels of CBCT expertise impacted
      the assessment accuracy. The participating orthodontists showed excellent
      consistency among themselves; however, poor agreement between their CBCT
      assessments compared with nasopharyngoscopy demonstrated that this sample of
      clinical orthodontists had poor diagnostic accuracy. Together, these findings
      suggest that orthodontists may make consistent and systematic errors in this type
      of evaluations.

PMID- 27871705
TI  - Applications of cone-beam computed tomography to assess the effects of labial
      crown morphologies and collum angles on torque for maxillary anterior teeth.
AB  - INTRODUCTION: Currently, cone-beam computed tomography (CBCT) has been widely
      used because of its capacity to evaluate the anatomic structures of the maxilla,
      mandible, and teeth in 3 dimensions. However, articles about the use of CBCT to
      evaluate the relationships between the morphology of individual teeth and torque
      expression remain rare. In this study, we aimed to determine the influence of
      labial crown morphologies and collum angles on torque for maxillary anterior
      teeth using CBCT. METHODS: A total of 206 extracted maxillary anterior teeth were
      selected to establish scanning models using dental wax, and they were scanned by
      CBCT. Three-dimensionally reconstructed images and median sagittal sections of
      the teeth were digitized and analyzed with AutoCAD software (Autodesk, San
      Rafael, Calif). The angle alpha, formed by the intersection of the tangent at a
      certain vertical height on the labial surface from the incisal edge with the
      crown long axis, and the collum angle, were measured. RESULTS: The variations in
      angle alpha at different heights from the incisal edge for the same type of tooth
      were statistically significantly different (P <0.001). Moreover, the variations
      between collum angles and 0 degrees  for any type of maxillary anterior tooth
      were statistically significant (P <0.01). CONCLUSIONS: This study suggested that
      there are great differences in labial crown morphologies and collum angles for
      maxillary anterior teeth between persons, indicating that the morphologies of
      these teeth do play important roles in torque variations.

PMID- 27871706
TI  - Retrospective study of maxillary sinus dimensions and pneumatization in adult
      patients with an anterior open bite.
AB  - INTRODUCTION: The aim of this study was to evaluate differences in the maxillary
      sinus floor levels between adults with an anterior open bite and those without.
      METHODS: This retrospective study included 30 subjects: 15 adults with an
      anterior open bite (mean age, 21.5 +/- 4.3 years) and 15 control subjects with
      normal occlusion (mean age, 21.7 +/- 3.1 years). Cone-beam computed tomography
      and lateral cephalograms were analyzed before treatment. RESULTS: The open-bite
      group exhibited a significantly greater maxillary posterior alveolar height (P
      <0.05). The craniocaudal heights of the maxillary sinus in the region between the
      first and second molars and between the second premolar and first molar were
      significantly greater in the open bite group (40.5 and 39.0 mm, respectively)
      than in the control group (36.7 and 34.7 mm, respectively; P <0.05 for both). The
      basal bone heights in the regions between the first and second molars, the second
      premolar and first molar, and the first and second premolars were significantly
      smaller in the open-bite group than in the control group (P <0.001 for all).
      CONCLUSIONS: Vertical pneumatization of the maxillary sinus floor in the region
      between the first and second molars and between the second premolar and first
      molar is greater in adults with an anterior open bite than in those without,
      whereas basal bone height in the maxillary posterior region is lower in the open
      bite patients.

PMID- 27871707
TI  - Cone-beam computed tomography-synthesized cephalometric study of operated
      unilateral cleft lip and palate and noncleft children with Class III skeletal
      relationship.
AB  - INTRODUCTION: Our objective was to compare the craniofacial hard and soft tissue
      characteristics between children with operated unilateral cleft lip and palate
      (UCLP) and children with noncleft lip and palate (non-CLP) with a Class III
      skeletal relationship. METHODS: The study sample consisted of 30 subjects (18
      boys, 12 girls; mean age, 10.21 years) affected by UCLP and 30 non-CLP subjects
      (17 boys, 13 girls; mean age, 10.19 years) as the control group. All subjects
      were in the mixed dentition with a Class III skeletal relationship. Cone-beam
      computed tomography-synthesized cephalograms were traced and evaluated, and
      craniofacial hard and soft tissue morphologies were compared between the UCLP and
      non-CLP groups. RESULTS: Maxillary length and gonial angle were 2.66 mm shorter
      and 3.67 degrees  greater, respectively, in the UCLP group than those in the non
      CLP group. The SNA and SNB angles describing the sagittal positions of the
      maxilla and mandible, respectively, relative to the cranial base were
      significantly smaller in the UCLP group (P <0.001 and P = 0.003, respectively).
      However, the 2 groups had similar sagittal intermaxillary relationships with
      similar ANB angles (P = 0.669). In the vertical dimension, the mandibular plane
      angle and the growth direction vector were significantly greater in the UCLP
      group (P = 0.007 and P <0.001, respectively). Lastly, the UCLP group had a more
      concave soft tissue profile, manifested by a reduced facial convexity angle, as
      well as an acute nasolabial angle and a more protruded lower lip. CONCLUSIONS:
      Although the 2 groups had similar sagittal intermaxillary relationships, patients
      in the UCLP group had more retrusive maxillary and mandibular positions relative
      to the cranial base and more severe vertical discrepancies. Additionally, the
      soft tissue profiles of patients affected by UCLP were more concave, and the
      compensatory adaptation was less satisfactory.

PMID- 27871708
TI  - Treatment-associated changes in malocclusion and oral health-related quality of
      life: A 4-year cohort study.
AB  - INTRODUCTION: The impact of orthodontic treatment on oral health-related quality
      of life (OHRQoL) in adolescents being treated in orthodontic practices has not
      yet been explored longitudinally. The aim of this cohort study was to describe
      the changes in both malocclusion and OHRQoL with orthodontic treatment. METHODS:
      One hundred seventy-four patients (ages, 10-17 years; 64.4% girls; 81.6%
      European) underwent 2-arch, fixed-appliance treatment in a 4-year prospective
      study conducted across 19 specialist orthodontic practices throughout New
      Zealand. They were assessed before treatment, at debond (when 87.4% of the
      baseline sample were reassessed), and at a mean 21 months postdebond (when 59.4%
      of the baseline sample were reassessed). OHRQoL was measured using the Child
      Perceptions Questionnaire, and the Dental Aesthetic Index was used to measure
      occlusion. RESULTS: Among the 104 patients who took part in all 3 assessments,
      little change in OHRQoL overall was seen at the end of treatment, despite
      considerable improvement in malocclusion (with the mean Dental Aesthetic Index
      score falling from 35.9 at baseline to 21.3 at debond). The mean Child
      Perceptions Questionnaire 11-14 was slightly greater at debond, and this was most
      notable in the functional limitations subscale. By the end of the study (21
      months postdebond, on average), the decreases in Child Perceptions Questionnaire
      11-14 scores were all substantial, especially in the emotional well-being and
      social well-being subscales. CONCLUSIONS: Malocclusion affects orthodontic
      patients' OHRQoL before treatment. A temporary increase in symptomatic impacts
      seen by the debond stage appears to ameliorate with time, with the benefits of
      orthodontic treatment for OHRQoL manifesting themselves some months later.

PMID- 27871709
TI  - Cephalometric study of Class II Division 1 patients treated with an extended
      duration, reinforced, banded Herbst appliance followed by fixed appliances.
AB  - INTRODUCTION: The Herbst appliance has been used in the treatment of Class II
      malocclusions with deficient mandibles. Various protocols, including different
      durations of the orthopedic treatment phase and stepwise advancement of the
      mandible, have been advocated for increasing the orthopedic effects. The
      objective of this study was to investigate the skeletal and dental changes in
      patients treated with a reinforced banded Herbst appliance for an extended
      duration and fixed appliance therapy. METHODS: The study group consisted of 30
      patients (16 boys, 14 girls; mean age, 12.3 +/- 2.5 years) with Class II Division
      1 malocclusions who were successfully treated with the new Herbst protocol
      followed by fixed appliances. Lateral cephalometric radiographs were taken before
      treatment, at the completion of Herbst treatment, and after removal of fixed
      appliances. The average treatment times were 1.5 +/- 0.7 years for the Herbst
      treatment and 1.8 +/- 0.5 years for the fixed appliances. A control Class II
      sample from the Bolton-Brush study was used to subtract growth from treatment
      changes to determine the appliance effect. Data were analyzed using analysis of
      variance and the Tukey-Kramer test. RESULTS: After the Herbst treatment, the
      incisal relationships of all subjects had been overcorrected to end-to-end
      relationships. Overjet was reduced by 7.2 mm after subtracting changes from
      growth. The skeletal contribution was 2.5 mm (35%), and the dental contribution
      was 4.7 mm (65%). The molar relationship was overcorrected to a more Class I
      relationship by 7.5 mm. The Wits appraisal was improved by 4.2 mm. Vertically,
      overbite was decreased by 3.3 mm. The maxillary and mandibular molars were
      extruded by 1 mm. The occlusal plane rotated clockwise by 5 degrees  with little
      change in the mandibular plane angle. After the treatment with fixed appliances,
      the overjet correction was maintained at 7.6 mm. The skeletal contribution was
      2.9 mm (38%), and the dental contribution was 4.7 mm (62%). The molar
      relationship was corrected to a Class I relationship by 5.9 mm. The Wits
      appraisal was improved by 3.2 mm. Vertically, overbite was decreased by 4.2 mm.
      The maxillary and mandibular molars were extruded by 0.3 and 0.8 mm,
      respectively. The occlusal plane rotated clockwise by 1.2 degrees  with little
      change in the mandibular plane angle. CONCLUSIONS: Doubling the usual orthopedic
      treatment time with the reinforced Herbst appliance followed by fixed appliance
      therapy was effective in correcting Class II Division 1 malocclusions with excess
      overjet and overbite. In this sample of successfully treated patients, most
      changes after Herbst and fixed appliance therapy were dentoalveolar (62%).
      However, the skeletal changes attained in the orthopedic phase of treatment were
      maintained after fixed appliance therapy.

PMID- 27871710
TI  - Microbiological assessment of aerosol generated during debond of fixed
      orthodontic appliances.
AB  - INTRODUCTION: The aims of this study were to describe bacterial load and
      diversity of the aerosol created during enamel cleanup after the removal of fixed
      orthodontic appliances and to assess the effect of a preprocedural mouth rinse.
      METHODS: The study involved the sampling of ambient air adjacent to the patient's
      mouth during adhesive removal using a slow-speed handpiece and a spiral fluted
      tungsten carbide bur without water irrigation. Sampling was carried out during
      enamel cleanup with or without a preprocedural mouth rinse of either sterile
      water or chlorhexidine. Airborne particles were collected using a viable inertial
      impactor simulating the human respiratory tree. The bacteria collected were
      analyzed using both culture and molecular techniques. RESULTS: Bacteria produced
      during debond and enamel cleanup can reach all levels of the respiratory tree.
      The use of a preprocedural mouth rinse, either sterile water or chlorhexidine,
      increased the numbers and diversity of the bacteria in the air. CONCLUSIONS: When
      using a slow-speed handpiece and a spiral fluted tungsten carbide bur for enamel
      cleanup after orthodontic treatment, the bacterial load and diversity of the
      aerosol produced are lower when a preprocedural mouth rinse is not used.

PMID- 27871711
TI  - Comparisons of tooth sizes, dental arch dimensions, tooth wear, and dental
      crowding in Amazonian indigenous people.
AB  - INRODUCTION: Our objective was to assess tooth wear, arch dimensions, tooth
      sizes, and dental crowding in 4 remote indigenous villages on the Xingu River in
      Brazil. These populations have similar patterns of dietary habits and practice
      exclusive breast-feeding, whereas studies in human genetics show large
      intertribal genetic distances and low intratribal variations. METHODS: Dental
      casts of 107 subjects in the permanent dentition were evaluated. Tooth wear, arch
      dimensions, mesiodistal tooth widths, and the irregularity index of the incisors
      were obtained and compared using analysis of variance or the Kruskal-Wallis test
      (P <0.05). RESULTS: Tooth wear and tooth size in the mandible were similar among
      villages. Three groups were discriminated. The first group included the Xicrin
      Kayapo and Arara-Laranjal villages, since no significant difference was found
      between them. Larger tooth sizes and arch dimensions (P <0.001) were found in
      both jaws in the Assurini village compared with the Xicrin-Kayapo and Arara
      Laranjal villages; this resulted in similar dental crowding index values in these
      groups. The Arara-Iriri village, where a high coefficient of inbreeding had been
      reported, showed intermediate arch dimensions, with the mesiodistal tooth widths
      similar to those in the Xicrin-Kayapo and Arara-Laranjal villages. This scenario
      resulted in a group with the lowest irregularity index, close to 0. CONCLUSIONS:
      These Amazonian indigenous villagers, who have been genetically studied
      previously, showed large intergroup genetic variations and similar patterns of
      tooth wear. Thus, we suggest from the findings in this study that the etiology of
      dental crowding among the inhabitants of the Xingu River area is predominantly
      associated with variations in the dimensions of dental arches, related to genetic
      influences.

PMID- 27871712
TI  - Treatment with Twin-block appliance followed by fixed appliance therapy in a
      growing Class II patient.
AB  - A girl, aged 11 years 4 months, with a skeletal Class II pattern and a severe
      overjet (10 mm) was treated with a Twin-block appliance. After 9 months of
      appliance therapy, the skeletal Class II was overcorrected. After 26 months of
      retention, when the occlusion was stable and the growth rate was diminishing,
      fixed orthodontic appliances using temporary skeletal anchorage devices were
      initiated. The total active treatment time with fixed orthodontic appliances was
      30 months. Posttreatment records after 18 months demonstrated excellent
      stability: a functional occlusion and a pleasing facial balance. Cone-beam
      computed tomography was used to visualize temporomandibular joint adaptations
      after the functional and fixed orthodontic therapies.

PMID- 27871713
TI  - En-masse protraction of mandibular posterior teeth into missing mandibular
      lateral incisor spaces using a fixed functional appliance.
AB  - Protraction of mandibular posterior teeth requiring absolute anchorage has always
      been a challenge, especially when the space is located in the anterior region,
      since more teeth must be protracted. Traditionally, skeletal anchorage devices
      have been used for anchorage reinforcement during protraction. However, drawbacks
      such as requirement of a surgical step, inability to tolerate heavy forces, and
      patient willingness to undergo such surgical procedures can be limiting factors.
      Additionally, the mechanics involved can sometimes create undesirable side
      effects, thereby limiting their application in such situations. This report
      describes the use of a fixed functional appliance as an anchorage-reinforcement
      device for en-masse protraction of mandibular posterior teeth into a missing
      lateral incisor space.

PMID- 27871714
TI  - Surgical and orthodontic management of maxillary canine-lateral incisor
      transpositions.
AB  - Transposition of the maxillary canine and the lateral incisor is a complex dental
      anomaly to treat. The difficulty increases if the treatment aims to correct the
      transposition. These case reports describe 2 patients with transposition of the
      maxillary lateral incisor and canine. The first case involves bilateral
      incomplete transpositions, and the second is a complete transposition. The
      radiographic appearance of the canine was similar in the 2 patients. However, the
      treatments were distinct because of the 3-dimensional positions of the teeth. The
      first case involved palatally placed lateral incisor roots. To prevent resorption
      of the lateral incisors, the canines were moved into position buccally. In the
      second case, the lateral incisor root had a buccal position, and the canine crown
      was tractioned palatally. The position of the lateral incisor root was critical
      when electing the correct treatment and mechanics for each patient.

PMID- 27871715
TI  - Assessing agreement in measurements of orthodontic study models: Digital caliper
      on plaster models vs 3-dimensional software on models scanned by structured-light
      scanner.
AB  - INTRODUCTION: In this study we aimed to compare measurements on plaster models
      using a digital caliper, and on 3-dimensional (3D) digital models, produced using
      a structured-light scanner, using 3D software. METHODS: Fifty digital models were
      scanned from the same plaster models. Arch and tooth size measurements were made
      by 2 operators, twice. Calibration was done on 10 sets of models and checked
      using the Pearson correlation coefficient. Data were analyzed by error variances,
      repeatability coefficient, repeated-measures analysis of variance, and Bland
      Altman plots. RESULTS: Error variances ranged between 0.001 and 0.044 mm for the
      digital caliper method, and between 0.002 and 0.054 mm for the 3D software
      method. Repeated-measures analysis of variance showed small but statistically
      significant differences (P <0.05) between the repeated measurements in the arch
      and buccolingual planes (0.011 and 0.008 mm, respectively). There were no
      statistically significant differences between methods and between operators.
      Bland-Altman plots showed that the mean biases were close to zero, and the 95%
      limits of agreement were within +/-0.50 mm. Repeatability coefficients for all
      measurements were similar. CONCLUSIONS: Measurements made on models scanned by
      the 3D structured-light scanner were in good agreement with those made on
      conventional plaster models and were, therefore, clinically acceptable.

PMID- 27871716
TI  - It's not the same thing.

PMID- 27871717
TI  - The chi-square test.

PMID- 27871718
TI  - Azanon's disease. A 19th century epidemic of neurolathyrism in Spain.
AB  - The cultivation and consumption of grasspea (Lathyrus sativus) in Spain probably
      dates back centuries, especially during times of famine when the neurotoxic
      potential of this legume was expressed in the form of a spastic paraparesis known
      as neurolathyrism. Little known outside the country, the epidemic of
      neurolathyrism in the years following the Spanish Civil War (1936-1939) came to
      affect more than a thousand people. In late 1872, during the Six Years
      Revolutionary Term, young Alejandro San Martin Satrustegui (1847-1908), then
      editor of the popular weekly El Siglo Medico, travelled to Azanon, a remote
      village in the province of Guadalajara, to clarify a so-far unknown disease. We
      analysed the original article published in 1873 by San Martin, as well as
      communications sent by El Siglo Medico readers reporting similar cases in many
      other Castilian provinces. San Martin's neurological findings in seven personally
      examined cases were astonishingly accurate; he concluded the subjects'
      neurological deficits resulted from injury to the lateral columns in the lower
      portion of the spinal cord. Description of the clinical findings provided both by
      San Martin, and by the readers of El Siglo Medico, leave no doubt as to the
      diagnosis of neurolathyrism. However, none suspected the patient's staple food
      was the determinant cause of the disease. San Martin proposed the eponym Azanon's
      disease for lack of a better name the same year (1873) in which Cantani in Italy
      introduced the term lathyrism. The epidemic of neurolathyrism that affected many
      Castilian towns represents one of the best-documented in Europe during the last
      third of the 19th century.

PMID- 27871719
TI  - [Work satisfaction and exhaustion among psychiatrists in psychiatric emergency
      services].
AB  - BACKGROUND AND AIM: Psychiatric emergency services (PES) have recently occupied a
      new and growing place in the landscape of mental health services. However, few
      data are available on the way psychiatrists practice in the PES. Our aim was to
      survey psychiatrists working in PES, focusing on their job satisfaction and the
      theoretical models they use in their everyday practice. METHOD: We sent a survey
      to a sample of 508 psychiatrists working in PES in France. RESULTS: Two hundred
      and thirty-seven psychiatrists returned the survey, yielding a response rate of
      47%. On a 0 to 10 scale, the mean level of job satisfaction was 6.7 (SD: 1.92).
      Participants reported that facing a variety of clinical situations and playing a
      key-coordinating role in the mental health system were the two most specific
      features of emergency psychiatry. The main sources of dissatisfaction were
      organizational issues and stressful clinical experiences, including violence or
      hostility. Sixty-three percent (n=150) of participants reported using more than
      two theoretical models in their practice, while the use of crisis models was
      reported by almost 40% of them. When assessed for suggestions to improve the PES,
      the majority of participants indicated that efforts should be focused on
      organizational factors. CONCLUSION: While emergency psychiatry could appear as an
      ungrateful practice, the majority of psychiatrists who responded to our survey
      reported satisfaction with their work and highlighted its unique particularities.
      Future research and collaborations are needed to identify organizational models
      of PES and their better integration in mental health networks.

PMID- 27871720
TI  - [Guidelines for the prescription of mood stabilizers for adolescents: A
      literature review].
AB  - INTRODUCTION: Adolescence is a unique phase of the human developmental process.
      In adolescents, psychotropic medications may have different efficacy and
      tolerance profiles compared to those at other stages of the lifespan. Mood
      stabilizers are a complex pharmacological category including lithium, some
      anticonvulsants, and some second generation antipsychotics. Focusing on this
      class of pharmacological agents, we aim to answer the following questions: in
      which indications and according to which modalities should mood stabilizers be
      prescribed during adolescence? METHODS: Information was sought from the websites
      of the French Haute Autorite de sante (HAS) and Agence nationale de securite du
      medicament et des produits de sante (ANSM), the American Food and Drug
      Administration (FDA) and the British National Institute for Health and Clinical
      Excellence (NICE). Guidelines from the American Academy of Child and Adolescent
      Psychiatry (AACAP) were also reviewed. Additional articles were found using
      PubMed and Google Scholar. We assumed that guidelines published by a national
      institute were the most relevant, second information from medical academies, then
      literature reviews, and finally single studies. Practical prescription data were
      also sought from the French Vidal Drug Dictionary. RESULTS: For bipolar disorder
      in adolescents, lithium has been the first drug licensed in France (from the age
      of 16) and in the USA (from the age of 12), with indications for acute mania and
      preventive treatment. Benefits for impulsive and self-aggressive behaviour
      disorders (especially relevant in case of borderline personality disorder) have
      also been documented, although lithium has not been licensed in any country for
      those indications. Extended-release tablets are usually used, at doses targeting
      for a lithiemia between 0.8 and 1.2mEq/L 12hours after last intake. Because of a
      narrow therapeutic window and potential side effects (especially nephrotoxicity),
      lithium prescription requires regular blood tests and good treatment compliance.
      None of the anticonvulsants has been licensed by a national drug administration
      as a mood stabilizer in adolescents. However, the AACAP recommends valproate as a
      first line treatment for mania, even though the NICE and the ANSM caution that
      valproate should not be used by women of child bearing age. Besides its
      teratogenic and endocrine side effects, valproate exposes one to the risk of
      hepatic toxicity. That is why regular liver function tests should be prescribed
      when valproate is chosen. According to the AACAP, carbamazepine (which is
      licensed for the treatment of mania in adults) is not a first line treatment for
      adolescents. Indeed, no clinical study has demonstrated its efficacy on manic
      episodes in adolescents. Moreover, carbamazepine exposes one to the risk of
      agranulocytosis. Lamotrigine has not been approved for adolescents, but some
      studies suggest its efficacy for bipolar depression (often a treatment-resistant
      phase) in this age group. Major side effects are the risk of Lyell or Stevens
      Johnsons syndrome (which usually occur within the first eight weeks of
      treatment). There is no need for biological tests, just clinical monitoring.
      Pharmacological interactions between lamotrigine and oral contraceptives require
      caution. Finally, the use of some second generation antipsychotics for bipolar
      disorder in adolescents has been approved by national drug administrations. In
      France, only aripiprazole is licensed for acute mania (from the age of 13). In
      the USA, aripiprazole is licensed from the age of 10 for acute mania and
      preventive treatment, while risperidone and quetiapine are licensed from the age
      of 10 for acute mania, and olanzapine is licensed from the age of 13 for acute
      mania. The AACAP recommends second generation antipsychotics as a first line
      treatment for bipolar disorder. Moreover, the AACAP and the NICE recommend second
      generation antipsychotics for behavioural disorders in adolescents. Recommended
      doses are usually lower and titration slower than for adults. As in adults,
      adverse effects are metabolic, motor and cognitive disorders. Moreover,
      hyperprolactinemia, sedation and weight gain are more frequent than in adults.
      DISCUSSION: Epidemiologic data for prescription of mood stabilizers in
      adolescents only partially concord with recommendations from drug administrations
      and scientific societies. On the one hand, there is a trend toward preferential
      prescription of second generation antipsychotics, on the other hand lithium is
      hardly prescribed to adolescents, less often than anticonvulsants. Thus, without
      approval from any drug administration, the anticonvulsants are often preferred to
      lithium (because of lithium's potential risks due to noncompliance or voluntary
      poisoning) and to second generation antipsychotics (because of their tolerance
      profile). Nevertheless, for prescribers it is a complex matter to compare side
      effects: the frequency and intensity of adverse effects is quite variable from
      one mood stabilizer to another, and such a thing as an expected value is
      therefore hard to define. Regardless of the medication chosen, compliance and
      therapeutic alliance are major issues. Compliance is especially low during
      adolescence (less than 40% according to a study on bipolar disorder). This lack
      of compliance has multiple determinants: poor acceptance or misunderstanding of
      the psychiatric disorder, indirect effects of bad relationships with parents and
      more generally adults, but also reckless behaviour or death wishes. Improving
      therapeutic alliance appears as a major challenge for health practitioners
      dealing with youth. One interesting path of research could be the therapeutic
      education programs using humanistic communication techniques (addressing both
      adolescents and their parents) which have already produced encouraging results.

PMID- 27871721
TI  - Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti
      Mullerian hormone in the differential diagnosis and follow-up of ovarian
      granulosa cell tumors.
AB  - OBJECTIVE: Evaluation of circulating tumor markers in ovarian cancer is crucial
      for optimal patient care. The goal of this study was to verify the most accurate
      circulating tumor markers for the diagnosis and follow-up of adult-type granulosa
      cell tumors (AGCTs). METHODS: The levels of circulating human epididymis protein
      4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin
      B and anti-Mullerian hormone (AMH), were measured in 135 samples from AGCT
      patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma
      (ENDO) patients. The levels were plotted with receiver operating characteristic
      (ROC) graphs, and the area under the curves (AUC) of the different markers were
      calculated and compared. RESULTS: HE4 levels were significantly lower in AGCTs
      than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients
      and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only
      in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was
      sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO,
      inhibin B and AMH performed similarly, and the combination of inhibin B and AMH
      increased the accuracy compared to either marker alone (sensitivity, 100%;
      specificity, 93%). Among AGCT patients, inhibin B was the best marker for
      detecting the presence of AGCT. CONCLUSIONS: HE4 and CA125 levels were low in
      AGCTs, and inhibin B was the most accurate circulating biomarker in
      distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single
      marker for AGCT follow-up.

PMID- 27871722
TI  - Video endoscopic inguinal lymphadenectomy (VEIL) for vulvar cancer.

PMID- 27871723
TI  - Safety and efficacy of single-agent bevacizumab-containing therapy in elderly
      patients with platinum-resistant recurrent ovarian cancer: Subgroup analysis of
      the randomised phase III AURELIA trial.
AB  - BACKGROUND: The AURELIA trial demonstrated significantly improved progression
      free survival (PFS) with bevacizumab added to chemotherapy for platinum-resistant
      ovarian cancer (PROC). METHODS: Patients with PROC were randomised to receive
      investigator-selected single-agent chemotherapy alone or with bevacizumab. Post
      hoc exploratory analyses assessed efficacy, safety and patient-reported outcomes
      according to age <65 versus >=65years. RESULTS: In the 133 patients (37%) aged
      >=65years, baseline hypertension was more frequent and ascites was less common
      than in patients <65years. The magnitude of PFS benefit from bevacizumab was
      similar in patients >=65 versus <65years (hazard ratio 0.44 [95% CI, 0.31-0.64]
      versus 0.49 [95% CI, 0.37-0.64], respectively, treatment-age interaction p=0.58),
      with similar improvements in response rates. Grade>=3 hypertension was more
      common with bevacizumab than chemotherapy alone in both subgroups, and more
      common in older than younger patients irrespective of treatment. However, there
      was no excess of other adverse events of specific interest for bevacizumab,
      including venous thromboembolic events, in older patients. More patients
      receiving bevacizumab in the younger but not the older subgroup showed improved
      gastrointestinal/abdominal symptoms. CONCLUSION: In exploratory analyses, PFS and
      response rate improvement with bevacizumab were consistent in older and younger
      patients. Grade>=3 hypertension was more common in elderly bevacizumab-treated
      patients; careful monitoring is recommended. Overall, bevacizumab-containing
      therapy was well tolerated in a selected population aged >=65years, suggesting a
      favourable benefit:risk profile. However, geriatric assessments are needed to
      improve selection of elderly patients potentially gaining symptom and quality of
      life improvements from bevacizumab-containing therapy. CLINICAL TRIALS
      REGISTRATION: ClinicalTrials.govNCT00976911.

PMID- 27871725
TI  - Organic and perovskite solar cells: Working principles, materials and interfaces.
AB  - In the last decades organic solar cells (OSCs) have been considered as a
      promising photovoltaic technology with the potential to provide reasonable power
      conversion efficiencies combined with low cost and easy processability.
      Unexpectedly, Perovskite Solar Cells (PSCs) have experienced unprecedented rise
      in Power Conversion Efficiency (PCE) thus emerging as a highly efficient
      photovoltaic technology. OSCs and PSCs are two different kind of devices with
      distinct charge generation mechanism, which however share some similarities in
      the materials processing, thus standard strategies developed for OSCs are
      currently being employed in PSCs. In this article, we recapitulate the main
      processes in these two types of photovoltaic technologies with an emphasis on
      interfacial processes and interfacial modification, spotlighting the materials
      and newest approaches in the interfacial engineering. We discuss on the relevance
      of well-known materials coming from the OSCs field, which are now being tested in
      the PSCs field, while maintaining a focus on the importance of the material
      design for highly efficient, stable and accessible solar cells.

PMID- 27871724
TI  - The palliative care needs of patients with idiopathic pulmonary fibrosis: A
      qualitative study of patients and family caregivers.
AB  - OBJECTIVES: To explore the perceptions of palliative care (PC) needs in patients
      with idiopathic pulmonary fibrosis (IPF) and their caregivers. BACKGROUND: IPF
      carries a poor prognosis with most patients succumbing to their illness at a rate
      comparable to aggressive cancers. No prior studies have comprehensively explored
      perceptions of PC needs from those currently living with the disease, caring for
      someone living with the disease, and who cared for a deceased family member.
      METHODS: Thematic analysis of focus group content was obtained from thirteen
      participants. RESULTS: Four themes described frustration with the diagnostic
      process and education received, overwhelming symptom burden, hesitance to engage
      in advance care planning, and comfort in receiving care from pulmonary specialty
      center because of resources. CONCLUSIONS: Findings support that patients and
      caregivers have informational needs and high symptom burden, but limited
      understanding of the potential benefits of PC. Future studies are needed to
      identify optimal ways to introduce early PC.

PMID- 27871726
TI  - Identification and determination of chlorinated azoles in sludge using liquid
      chromatography quadrupole time-of-flight and triple quadrupole mass spectrometry
      platforms.
AB  - Four antimycotic drugs (tioconazole, TCZ; sertaconazole, STZ; fenticonazole, FTZ
      and itraconazole, ITZ) and the fungicide imazalil (IMZ) are determined in sludge
      from sewage treatment plants (STPs) following a bottom-up analytical strategy.
      First, sludge extracts, obtained under different sample preparation conditions,
      were analyzed by liquid chromatography (LC) quadrupole time-of-flight (QTOF) mass
      spectrometry (MS). A non-target search strategy, combined with the use of the
      chlorine mass filter, permitted to detect several chlorinated pollutants
      including the above referred azoles, which either had not been previously
      reported (TCZ, STZ, FTZ and ITZ), or scarcely investigated (IMZ), in this
      environmental compartment. Then, the sample preparation procedure was validated
      using standards of these compounds and their sensitive and selective
      determination was performed by LC-MS/MS, based on a QqQ system. Under final
      working conditions, quantitative extraction yields were attained with negligible
      changes in ionization efficiencies between sample extracts and standards;
      therefore, the above compounds were quantified against authentic standard
      solutions, with absolute recoveries in the range from 75 to 124%, achieving a
      limit of quantification of 2ngg-1. Analysis of sludge from 10 municipal STPs
      demonstrated the ubiquity of the identified chlorinated azoles with average
      concentrations from 31ngg-1, for IMZ, to more than 200ngg-1, for ITZ.

PMID- 27871727
TI  - Critical Material Attributes of Strip Films Loaded With Poorly Water-Soluble Drug
      Nanoparticles: II. Impact of Polymer Molecular Weight.
AB  - Recent work established polymer strip films as a robust platform for delivery of
      poorly water-soluble drug particles. However, a simple means of manipulating rate
      of drug release from films with minimal impact on film mechanical properties has
      yet to be demonstrated. This study explores the impact of film-forming polymer
      molecular weight (MW) and concentration on properties of polymer films loaded
      with poorly water-soluble drug nanoparticles. Nanoparticles of griseofulvin, a
      model Biopharmaceutics Classification System class II drug, were prepared in
      aqueous suspension via wet stirred media milling. Aqueous solutions of 3
      viscosity grades of hydroxypropyl methylcellulose (14, 21, and 88 kDa) at 3
      viscosity levels (~9500, ~12,000, and ~22,000 cP) were mixed with drug
      suspension, cast, and dried to produce films containing griseofulvin
      nanoparticles. Few differences in film tensile strength or elongation at break
      were observed between films within each viscosity level regardless of polymer MW
      despite requiring up to double the time to achieve 100% drug release. This
      suggests film-forming polymer MW can be used to manipulate drug release with
      little impact on film mechanical properties by matching polymer solution
      viscosity. In addition, changing polymer MW and concentration had no negative
      impact on drug content uniformity or nanoparticle redispersibility.

PMID- 27871730
TI  - Patient empowerment: What does it really mean?

PMID- 27871728
TI  - The CHRNA5-A3-B4 Gene Cluster and Smoking: From Discovery to Therapeutics.
AB  - Genome-wide association studies (GWASs) have identified associations between the
      CHRNA5-CHRNA3-CHRNB4 gene cluster and smoking heaviness and nicotine dependence.
      Studies in rodents have described the anatomical localisation and function of the
      nicotinic acetylcholine receptors (nAChRs) formed by the subunits encoded by this
      gene cluster. Further investigations that complemented these studies highlighted
      the variability of individuals' smoking behaviours and their ability to adjust
      nicotine intake. GWASs of smoking-related health outcomes have also identified
      this signal in the CHRNA5-CHRNA3-CHRNB4 gene cluster. This insight underpins
      approaches to strengthen causal inference in observational data. Combining
      genetic and mechanistic studies of nicotine dependence and smoking heaviness may
      reveal novel targets for medication development. Validated targets can inform
      genetic therapeutic interventions for smoking cessation and tobacco-related
      diseases.

PMID- 27871731
TI  - President Trump.

PMID- 27871729
TI  - An Integrative Tinnitus Model Based on Sensory Precision.
AB  - Tinnitus is a common disorder that often complicates hearing loss. Its mechanisms
      are incompletely understood. Current theories proposing pathophysiology from the
      ear to the cortex cannot individually - or collectively - explain the range of
      experimental evidence available. We propose a new framework, based on predictive
      coding, in which spontaneous activity in the subcortical auditory pathway
      constitutes a 'tinnitus precursor' which is normally ignored as imprecise
      evidence against the prevailing percept of 'silence'. Extant models feature as
      contributory mechanisms acting to increase either the intensity of the precursor
      or its precision. If precision (i.e., postsynaptic gain) rises sufficiently then
      tinnitus is perceived. Perpetuation arises through focused attention, which
      further increases the precision of the precursor, and resetting of the default
      prediction to expect tinnitus.

PMID- 27871732
TI  - Crisis point for radiology and oncology workforces.

PMID- 27871733
TI  - Measles vaccination: global progress, local challenges.

PMID- 27871734
TI  - The black box warning on philanthrocapitalism.

PMID- 27871736
TI  - Offline: Planetary health-gains and challenges.

PMID- 27871737
TI  - West African countries focus on post-Ebola recovery plans.

PMID- 27871735
TI  - Zoonotic tuberculosis in Africa: challenges and ways forward.

PMID- 27871738
TI  - Profile: The Kirby Institute celebrates 30 years.

PMID- 27871739
TI  - David Cooper: Australia's fighter against HIV and discrimination.

PMID- 27871740
TI  - Setting up childhood obesity policies in Europe.

PMID- 27871741
TI  - Pride in autistic diversity: against treatment or for inclusion?

PMID- 27871742
TI  - New poliovirus vaccine schedules.

PMID- 27871743
TI  - New poliovirus vaccine schedules - Authors' reply.

PMID- 27871744
TI  - Editorial Comment.

PMID- 27871745
TI  - The effect of dissolved oxygen concentration (DO) on oxygen diffusion and
      bacterial community structure in moving bed sequencing batch reactor (MBSBR).
AB  - The effect of dissolved oxygen concentration (DO) on simultaneous nitrification
      and denitrification was studied in a moving bed sequencing batch reactor (MBSBR)
      by microelectrode measurements and by real-time PCR. In this system, the biofilm
      grew on polyurethane foam carriers used to treat municipal sewage at five DO
      concentrations (1.5, 2.5, 3.5, 4.5 and 5.5 mg/L). The results indicated that the
      MBSBR exhibited good removal of chemical oxygen demand (92.43%) and nitrogen
      (83.73%) when DO concentration was 2.5 mg/L. Increasing the oxygen concentration
      in the reactor was inhibitory to denitrification. Microelectrode measurements
      showed that the thickness of oxygen penetration increased from 1.2 to 2.6 mm when
      the DO concentration (from 1.5 mg/L to 5.5 mg/L) in the system increased. Oxygen
      diffusion was not significantly limited by the boundary layer surrounding the
      carrier and had the largest slope when DO concentration was 2.5 mg/L. The real
      time PCR analysis indicated that the amount of the ammonia-oxidizing bacteria and
      nitrite-oxidizing bacteria increased slowly as DO concentration increased. The
      proportions of ammonia-oxidizing bacteria and nitrite-oxidizing bacteria, as a
      percentage of the total bacteria, were low with average values of 0.063% and
      0.67%, respectively. When the DO concentration was 2.5 mg/L, oxygen diffusion was
      optimal and ensured the optimal bacterial community structure and activity; under
      these conditions, the MBSBR was efficient for total inorganic nitrogen removal.
      Changing the DO concentration could alter the aerobic zone and the bacterial
      community structure in the biofilm, directly influencing the simultaneous
      nitrification and denitrification activity in MBSBRs.

PMID- 27871746
TI  - A practical model for sunlight disinfection of a subtropical maturation pond.
AB  - Maturation ponds are a type of waste stabilisation pond (WSP) designed to reduce
      carbon, nutrients and pathogens in the final stages of a WSP wastewater treatment
      system. In this study, a one-dimensional plug-flow pond model is proposed to
      predict temperature and E. coli concentration distributions and overall pond
      disinfection performance. The model accounts for the effects of vertical mixing
      and ultraviolet light-dependent die-off rate kinetics. Measurements of radiation,
      wind-speed, humidity and air temperature are recorded for model inputs and good
      agreement with measured vertical temperature distributions and outlet E. coli
      concentrations is found in an operational, subtropical maturation pond.
      Measurements and the model both show a diurnal pattern of stratification during
      daylight hours and natural convective mixing at night on days corresponding to
      low wind speeds, strong heat input from solar radiation and clear night skies. In
      the evenings, the thermal stratification is shown to collapse due to surface
      energy loss via longwave radiation which triggers top-down natural convective
      mixing. The disinfection model is found to be sensitive to the choice of die-off
      kinetics. The diurnal mixing pattern is found to play a vital role in the
      disinfection process by ensuring that pathogens are regularly transported to the
      near-surface layer where ultraviolet light penetration is effective. The model
      proposed in this paper offers clear advantages to pond designers by including
      geographical specific, time-varying boundary conditions and accounting for the
      important physical aspects of vertical mixing and sunlight inactivation
      processes, yet is computationally straightforward.

PMID- 27871747
TI  - Impact of external carbon dose on the removal of micropollutants using methanol
      and ethanol in post-denitrifying Moving Bed Biofilm Reactors.
AB  - Addition of external carbon sources to post-denitrification systems is frequently
      used in wastewater treatment plants to enhance nitrate removal. However, little
      is known about the fate of micropollutants in post-denitrification systems and
      the influence of external carbon dosing on their removal. In this study, we
      assessed the effects of two different types and availability of commonly used
      carbon sources -methanol and ethanol- on the removal of micropollutants in
      biofilm systems. Two laboratory-scale moving bed biofilm reactors (MBBRs),
      containing AnoxKaldnes K1 carriers with acclimated biofilm from full-scale
      systems, were operated in continuous-flow using wastewater dosed with methanol
      and ethanol, respectively. Batch experiments with 22 spiked pharmaceuticals were
      performed to assess removal kinetics. Acetyl-sulfadiazine, atenolol, citalopram,
      propranolol and trimethoprim were easily biotransformed in both MBBRs
      (biotransformations rate constants kbio between 1.2 and 12.9 L gbiomass-1 d-1),
      13 compounds were moderately biotransformed (rate constants between 0.2 and 2 L
      gbiomass-1 d-1) and 4 compounds were recalcitrant. The methanol-dosed MBBR showed
      higher kbio (e.g., 1.5-2.5-fold) than in the ethanol-dosed MBBR for 9 out of the
      22 studied compounds, equal kbio for 10 compounds, while 3 compounds (i.e.,
      targeted sulfonamides) were biotransformed faster in the ethanol-dosed MBBR.
      While biotransformation of most of the targeted compounds followed first-order
      kinetics, removal of venlafaxine, carbamazepine, sulfamethoxazole and
      sulfamethizole could be described with a cometabolic model. Analyses of the
      microbial composition in the biofilms using 16S rRNA amplicon sequencing revealed
      that the methanol-dosed MBBR contained higher microbial richness than the one
      dosed with ethanol, suggesting that improved biotransformation of targeted
      compounds could be associated with higher microbial richness. During continuous
      flow operation, at conditions representative of full-scale denitrification
      systems (hydraulic residence time = 2 h), the removal efficiencies of
      micropollutants were below 35% in both MBBRs, with the exception of atenolol and
      trimethoprim (>80%). Overall, this study demonstrated that MBBRs used for post
      denitrification could be optimized to enhance the biotransformation of a number
      of micropollutants by accounting for optimal carbon sources and extended
      residence time.

PMID- 27871748
TI  - Mass balance analyses of nutrients on California dairies to evaluate data quality
      for regulatory review.
AB  - Effective regulations may help reduce nitrate contamination of groundwater from
      agriculture. Dairy farmers in California must maintain a ratio below 1.4 of total
      nitrogen (N) applied to total N-removed (N-Ratio) on cropland receiving manure
      application. In annual reports to the regulatory agency, farmers detail nutrients
      applied to cropland, removed in harvests, and exported off farm. Data were
      extracted from all available annual reports for 62 dairies from 2011, 2012, and
      2013. Excretions of N, phosphorus (P), and potassium (K) were calculated using
      reported herd demographics and standard excretion equations from the American
      Society of Agricultural and Biological Engineers. Calculated nutrient excretion
      values were compared to the reported values of manure nutrients applied to
      cropland and exported off farm. Reported N-Ratios were compared to mass balance
      simulations exploring variable crop yields and alfalfa management. In the
      nutrient excretion balance, the distribution of the percent of N and P recovered
      in manures applied or exported peaked at 24% (median=31%) and 26% (median=53%) of
      excreted, respectively. The distribution of recovered K was fairly uniform from
      0% to 300% (median=146%) of excreted K. In N-ratio simulations, 62% and 66% of
      all reported N-ratios were lower than their respective simulated N-ratio,
      assuming alfalfa crops received no N fertilization and minimal fertilization (26%
      of N-removed in harvest) respectively. When simulated crop yields were normally
      (sd=0.25) or Student's t distributed (df=154) around expected crop yields, 28%
      and 57% of all reported ratios fell within the 95% confidence interval of the
      simulations, respectively. Low and erratic recovery rates of excreted P and K
      existed. Additionally, reported N-Ratios were generally lower and more varied
      than necessary for farmers to maintain crop yields while complying with
      regulations. Greater understanding of low recovery rates is needed before data
      are used to assess the impact of regulations.

PMID- 27871749
TI  - The effects of metallic engineered nanoparticles upon plant systems: An analytic
      examination of scientific evidence.
AB  - Recent evidence for the effects of metallic engineered nanoparticles (ENPs) on
      plants and plant systems was examined together with its implications for other
      constituents of the Society-Environment-Economy (SEE) system. In this study, we
      were particularly interested to determine whether or not metallic ENPs have both
      stimulatory and inhibitory effects upon plant performance. An emphasis was made
      to analyze the scientific evidence on investigations examining both types of
      effects in the same studies. Analysis of evidence demonstrated that metallic ENPs
      have both stimulatory and inhibitory effects mostly in well-controlled
      environments and soilless media. Nano zero-valent iron (nZVI) and Cu ENPs have
      potential for use as micronutrients for plant systems, keeping in mind the proper
      formulation at the right dose for each type of ENP. The concentration levels for
      the stimulatory effects of Cu ENPs are lower than for those for nZVI. Newer
      findings showed that extremely smaller concentrations of Au ENPs (smaller than
      those for nZVI and Cu ENPs) induce positive effects for plant growth, which is
      attributed to effects on secondary metabolites. Ag ENPs have demonstrated their
      usage as antimicrobial/pesticidal agents for plant protection; however,
      precautions should be taken to avoid higher concentrations not only for plant
      systems, but also, other constituents in the SEE. Further research is warranted
      to investigate the stimulatory and inhibitory effects of metallic ENPs in soil
      media in order to broaden the horizon of sustainable agriculture production in
      terms of higher and safer yields so as to meet the food requirements of human
      population.

PMID- 27871750
TI  - Biogeochemical and hydrological drivers of the dynamics of Vibrio species in two
      Patagonian estuaries.
AB  - The ecology of the most relevant Vibrio species for human health and their
      relation to water quality and biogeochemistry were studied in two estuaries in
      Argentinian Patagonia. Vibrio cholerae and Vibrio parahaemolyticus were reported
      in >29% of cases at the Rio Colorado and Rio Negro estuaries. Neither the
      pandemic serogroups of Vibrio cholerae O1, Vibrio cholerae O139 nor the cholera
      toxin gene were detected in this study. However, several strains of V. cholerae
      (not O1 or O139) are able to cause human disease or acquire pathogenic genes by
      horizontal transfer. Vibrio vulnificus was detected only in three instances in
      the microplankton fraction of the Rio Negro estuary. The higher salinity in the
      Rio Colorado estuary and in marine stations at both estuaries favours an
      abundance of culturable Vibrio. The extreme peaks for ammonium, heterotrophic
      bacteria and faecal coliforms in the Rio Negro estuary supported a marked impact
      on sewage discharge. Generally, the more pathogenic strains of Vibrio have a
      faecal origin. Salinity, pH, ammonium, chlorophyll a, silicate and
      carbon/nitrogen ratio of suspended organic particulates were the primary factors
      explaining the distribution of culturable bacteria after distance-based linear
      models. Several effects of dissolved organic carbon on bacterial distribution are
      inferred. Global change is expected to increase the trophic state and the
      salinisation of Patagonian estuaries. Consequently, the distribution and
      abundance of Vibrio species is projected to increase under future changing
      baselines. Adaptation strategies should contribute to sustaining good water
      quality to buffer climate- and anthropogenic- driven impacts.

PMID- 27871751
TI  - Regional assessment of concentrations and sources of pharmaceutically active
      compounds, pesticides, nitrate, and E. coli in post-glacial aquifer environments
      (Canada).
AB  - There is growing concern worldwide about the exposure of groundwater resources to
      pharmaceutically active compounds (PhACs) and agricultural contaminants, such as
      pesticides, nitrate, and Escherichia coli. For regions with a low population
      density and an abundance of water, regional contamination assessments are not
      carried out systematically due to the typically low concentrations and high costs
      of analyses. The objectives of this study were to evaluate regional-scale
      contaminant distributions in untreated groundwater in a rural region of Quebec
      (Canada). The geological and hydrogeological settings of this region are typical
      of post-glacial regions around the world, where groundwater flow can be complex
      due to heterogeneous geological conditions. A new spatially distributed
      Anthropogenic Footprint Index (AFI), based on land use data, was developed to
      assess surface pollution risks. The Hydrogeochemical Vulnerability Index (HVI)
      was computed to estimate aquifer vulnerability. Nine wells had detectable
      concentrations of one to four of the 13 tested PhACs, with a maximum
      concentration of 116ng.L-1 for benzafibrate. A total of 34 of the 47 tested
      pesticides were detected in concentrations equal to or greater than the detection
      limit, with a maximum total pesticide concentration of 692ng.L-1. Nitrate
      concentrations exceeded 1mg.L-1 N-NO3 in 15.3% of the wells, and the Canadian
      drinking water standard was exceeded in one well. Overall, 13.5% of the samples
      had detectable E. coli. Including regional-scale sources of pollutants to the
      assessment of aquifer vulnerability with the AFI did not lead to the
      identification of contaminated wells, due to the short groundwater flow paths
      between recharge and the sampled wells. Given the occurrence of contaminants, the
      public health concerns stemming from these new data on regional-scale PhAC and
      pesticide concentrations, and the local flow conditions observed in post-glacial
      terrains, there is a clear need to investigate the sources and behaviours of
      local-scale pollutants.

PMID- 27871752
TI  - Public acceptance of management methods under different human-wildlife conflict
      scenarios.
AB  - Wildlife management seeks to minimise public controversy for successful
      application of wildlife control methods. Human dimensions research in wildlife
      seeks a better understanding of public preferences for effective human-wildlife
      conflict resolution. In face to face interviews, 630 adults in Greece were asked
      to rate on a 5-point Likert-like scale their acceptance of 3 management methods,
      i.e., do nothing, non-lethal control, and lethal control, in the context of 5
      human-wildlife conflict scenarios: 1) corvids damage crops; 2) starlings damage
      crops; 3) starlings foul urban structures; 4) coypus damage crops; and 5) coypus
      transfer disease. Univariate GLMs determined occupation, hunting membership and
      their interaction as the stronger predictors of public acceptance, generating 4
      stakeholder groups: the general public, farmers, hunters, and farmers-hunters.
      Differences in acceptance and consensus among stakeholder groups were assessed
      using the Potential for Conflict Index2 (PCI2). All 4 stakeholder groups agreed
      that doing nothing was unacceptable and non-lethal control acceptable in all 5
      scenarios, with generally high consensus within and between groups. The lethal
      control method was more controversial and became increasingly more acceptable as
      the severity of scenarios was increased and between non-native and native
      species. Lethal control was unacceptable for the general public in all scenarios.
      Farmers accepted lethal methods in the corvids and starlings scenarios, were
      neutral in the coypus damage crops scenario, whereas they accepted lethal control
      when coypus transfer disease. Hunters' opinion was neutral in the corvids,
      starlings and coypus damage crops and starlings foul urban structures scenarios,
      but they accepted lethal methods in the coypus transfer disease scenario. Farmers
      hunters considered lethal control acceptable in all 5 scenarios. Implications
      from this study could be used for designing a socio-ecological approach which
      incorporates wildlife management with public interests. The studied species have
      a wide distribution, therefore present findings might also prove useful
      elsewhere.

PMID- 27871753
TI  - Role of three different plants on simultaneous salt and nutrient reduction from
      saline synthetic wastewater in lab-scale constructed wetlands.
AB  - Constructed Wetlands (CWs) can be a valuable technology to treat high salinity
      wastewaters but it is not known their potential for removal of both nutrients and
      salt, and the type of plants to use. This study evaluated the effect of three
      plants on salt reduction and simultaneous nutrient removal in CWs microcosms with
      expanded clay and in hydroponic conditions. Initial values of the synthetic
      wastewater tested were EC=15dSm-1, SAR=151; NH4+-N=24mgL-1; PO43--P=30mgL-1 and
      NO3--N=34mgL-1. With expanded clay CW removal efficiency for NH4+-N was 21, 88
      and 85%, while for NO3--N, it was 4, 56 and 68% for Spartina maritima, Juncus
      maritimus and Arundo donax, respectively. PO43--P was adsorbed completely in the
      expanded clay. However, in hydroponic system, removal efficiencies for NH4+-N
      were 53 and 50%, while PO43--P removal was 89 and -14% for Spartina maritima and
      Juncus maritimus, respectively. Nutrient removal in planted microcosms was
      statistically higher than unplanted controls for NH4+-N and PO43--P. However,
      salt removal was apparent in the hydroponic system only after 23days of HRT,
      despite clear salt excretion visible in both Spartina maritima and Juncus
      maritimus. This study demonstrates the potential of two halophytic plants for
      saline wastewater treatment. However, salt removal in such a scenario could not
      be well documented and might prove to be impractical in future work.

PMID- 27871754
TI  - Farmland-atmosphere feedbacks amplify decreases in diffuse nitrogen pollution in
      a freeze-thaw agricultural area under climate warming conditions.
AB  - Although climate warming and agricultural land use changes are two of the primary
      instigators of increased diffuse pollution, they are usually considered
      separately or additively. This likely lead to poor decisions regarding climate
      adaptation. Climate warming and farmland responses have synergistic consequences
      for diffuse nitrogen pollution, which are hypothesized to present different
      spatio-temporal patterns. In this study, we propose a modeling framework to
      simulate the synergistic impacts of climate warming and warming-induced farmland
      shifts on diffuse pollution. Active accumulated temperature response for
      latitudinal and altitudinal directions was predicted based on a simple agro
      climate model under different temperature increments (?T0 is from 0.8 degrees C
      to 1.4 degrees C at an interval of 0.2 degrees C). Spatial distributions of
      dryland shift to paddy land were determined by considering accumulated
      temperature. Different temperature increments and crop distributions were
      inserted into Soil and Water Assessment Tool model, which quantified the spatio
      temporal changes of nitrogen. Warming led to a decrease of the annual total
      nitrogen loading (2.6%-14.2%) in the low latitudes compared with baseline, which
      was larger than the decrease (0.8%-6.2%) in the high latitudes. The synergistic
      impacts amplified the decrease of the loading in the low and high latitudes at
      the sub-basin scale. Warming led to a decrease of the loading at a rate of
      0.35kg/ha/ degrees C, which was lower than the synergistic impacts (3.67kg/ha/
      degrees C) at the watershed level. However, warming led to the slight increase of
      the annual averaged NO3 (LAT) (0.16kg/ha/ degrees C), which was amplified by the
      synergistic impacts (0.22kg/ha/ degrees C). Expansion of paddy fields led to a
      decrease in the monthly total nitrogen loading throughout the year, but amplified
      an increase in the loading in August and September. The decreased response in
      spatio-temporal nitrogen patterns is substantially amplified by farmland
      atmosphere feedbacks associated with farmland shifts in response to warming.

PMID- 27871755
TI  - Multicontamination phenomena occur more often than expected in Mediterranean
      coastal watercourses: Study case of the Tet River (France).
AB  - Contaminants found in watercourses are not only the result of anthropogenic
      activities but also depend on river's seasonal hydrodynamics. This is
      particularly true in Mediterranean climate regions where long dry periods are
      interrupted by strong rainfalls. Storm events remobilize particles from soils and
      sediments and, as a consequence, the load of particulate matter in rivers can be
      quite considerable, severely affecting water quality. Nevertheless, an absence of
      fieldwork studies exists concerning the simultaneous dynamics of mixtures of
      pollutants in river waters, particularly during strong rainfalls and floods. Our
      study assessed the concentrations of six families of pollutants, including
      pesticides, at these events, and compared them to those observed at drought
      sampling periods. We have used as model a typical Mediterranean coastal river
      from Southeast France, the Tet River, whose hydrodynamics and major elements
      fluxes have been fairly investigated. As expected, our results show that chemical
      mixtures due to human activities occur and that they are particularly relevant
      during storm events. But the results of our study argue that exceptional
      multicontamination phenomena actually happen more often than expected because
      they are linked to recurrent sudden intense rainfall events in the Mediterranean.
      In particular, combined sewer overflows are responsible for this major issue in
      urbanized areas, whereas runoff and leaching will be the most important sources
      of pollutant mixtures occurring at flood flow peak. After an overview of the
      sources responsible for chronic multiple stressors events in regions under a
      Mediterranean climate regime worldwide, we revisit best management measures to
      reduce risks from the presence of chemical mixtures in the environment.

PMID- 27871756
TI  - Response of wastewater biofilm to CuO nanoparticle exposure in terms of
      extracellular polymeric substances and microbial community structure.
AB  - The growing production and application of CuO nanoparticles increase the chance
      that these particles will be released into wastewater treatment plants (WWTPs)
      and interact with microorganisms. However, the toxicity response mechanism of
      biofilm to NP exposure may be different from that of activated sludge due to the
      denser and stronger microbial aggregate structure of biofilm. Thus, in this
      study, the response to CuO NPs of wastewater biofilm collected from a rotating
      biological contactor was investigated. Short-term exposure (24h) to CuO NPs led
      to a great loss in cell viability, and SEM-EDS images revealed that the nano-CuO
      aggregates were not transformed to Cu-S species in the biofilm samples. In
      response, more extracellular polymeric substance (EPS) (especially loosely bound
      EPS) was produced in wastewater biofilm exposed to CuO NPs, with a higher content
      of protein compared to polysaccharides. The shifts of fluorescence intensity and
      peak locations in 3D-EEM fluorescence spectra indicated chemical changes of the
      EPS components. FT-IR analysis revealed that exposure to nano-CuO had more
      distinct effects on the functional groups of proteins and polysaccharides in LB
      EPS. Illumina sequencing of 16S rRNA gene amplicons revealed that CuO NPs
      enhanced bacterial diversity. The bacterial community structure significantly
      shifted, with a significantly increased abundance of Comamonas, a slight increase
      in Zoogloea, and a notable decrease in Flavobacterium. The shifts of these
      dominant genera may be associated with altered EPS production, which might result
      in microbial community function fluctuations. In conclusion, exposure to high
      concentrations of CuO NPs has the potential to shape wastewater biofilm bacterial
      community structure.

PMID- 27871757
TI  - An approach to the environmental prioritisation of volatile methylsiloxanes in
      several matrices.
AB  - Siloxane-based compounds are widely used in personal care, pharmaceutical and
      household products as well as in industrial applications. Among the wide variety
      of these chemicals, special attention has been given to volatile methylsiloxanes
      (VMSs). These compounds have been extensively detected in several environmental
      compartments, as they are not effectively removed from wastewater and may migrate
      through different matrices and being lipophilic, bioaccumulate and biomagnify in
      living organisms. In this work, a prioritisation methodology for several VMSs in
      different environmental matrices was applied, estimating a hazard quotient by
      combining exposure evaluation through measured or predicted environmental
      concentrations (MEC or PEC) and effects using ecotoxicity data to establish no
      effect concentrations (PNEC). VMSs show quite different hazard potentials in the
      environment: for linear VMSs it is not considerable, while for cyclic VMSs the
      hazard is disperse. D4 and D5 may have adverse effects in water, as well as D5
      and D6 in sediments. This first multi-matrix approach for the prioritisation of
      VMSs sets the ground for more accurate studies in the future, provided that more
      field-based data are reported.

PMID- 27871758
TI  - Rapid steroid withdrawal in kidney transplantation: living in HARMONY?

PMID- 27871761
TI  - Depression and Liver Transplant Survival.
AB  - BACKGROUND: Patients who underwent liver transplantation and experienced clinical
      depression have heretofore evinced lower survival rates when compared to
      nondepressed counterparts. OBJECTIVE: To investigate the hypothesis that
      transplant patients who seek and obtain medical treatment for depression would
      circumvent the prior reduced survival findings. METHODS: A total of 765 patients
      with liver transplants were scrutinized for complications following
      transplantation. Further, 104 patients experienced posttransplant depression as
      manifested by diagnosis and treatment by medical personnel. Survival analyses
      were conducted comparing hazard and survival curves for these selected
      individuals and the remainder of transplant patients. RESULTS: Contrary to prior
      data and consistent with the aforementioned hypothesis, median survival
      durations, survival curves, and hazard functions (controlling for age and
      prolonged posttransplant survival for the depressed patients were better.
      CONCLUSION: The improved survival for the depressed patients may simply be
      related to an amelioration of depressed symptoms via antidepressant medications.
      However, this interpretation would only be congruent with reduced hazard, not
      elevated survival, beyond the norm (median) for other transplant participants.
      Assuming the reliability and generalization of our findings, perhaps a reasonable
      and compelling interpretation is that combined with the effectiveness of
      antidepressant medications, the seeking and receiving treatment for depression is
      a type of proxy measure of a more global pattern of adherence to recommended
      posttransplant medical regimens.

PMID- 27871759
TI  - Rabbit-ATG or basiliximab induction for rapid steroid withdrawal after renal
      transplantation (Harmony): an open-label, multicentre, randomised controlled
      trial.
AB  - BACKGROUND: Standard practice for immunosuppressive therapy after renal
      transplantation is quadruple therapy using antibody induction, low-dose
      tacrolimus, mycophenolate mofetil, and corticosteroids. Long-term steroid intake
      significantly increases cardiovascular risk factors with negative effects on the
      outcome, especially post-transplantation diabetes associated with morbidity and
      mortality. In this trial, we examined the efficacy and safety parameters of rapid
      steroid withdrawal after induction therapy with either rabbit antithymocyte
      globulin (rabbit ATG) or basiliximab in immunologically low-risk patients during
      the first year after kidney transplantation. METHODS: In this open-label,
      multicentre, randomised controlled trial, we randomly assigned renal transplant
      recipients in a 1:1:1 ratio to receive either basiliximab induction with low-dose
      tacrolimus, mycophenolate mofetil, and steroid maintenance therapy (arm A), rapid
      corticosteroid withdrawal on day 8 (arm B), or rapid corticosteroid withdrawal on
      day 8 after rabbit ATG (arm C). The study was done in 21 centres across Germany.
      Only participants aged between 18 and 75 years with a low immunological risk who
      were scheduled to receive a single-organ renal transplant from either a living
      donor or a deceased donor were considered for enrolment. Patients receiving a
      second renal transplant were eligible, provided that the first allograft was not
      lost due to acute rejection within the first year after transplantation. Donor
      and recipient had to be ABO compatible. Grafts with pre-transplant existing donor
      specific human leukocyte antigen (HLA) antibodies were not eligible and the
      recipients had to have a panel-reactive antibody concentration of 30% or less.
      Pregnant women and nursing mothers were excluded from the study. The primary
      endpoint was the incidence of biopsy-proven acute rejection (BPAR) at 12 months.
      All analyses were done by intention-to-treat. This trial is registered with
      ClinicalTrials.gov, number NCT00724022. FINDINGS: Between Aug 7, 2008, and Nov
      30, 2013, 615 patients were randomly assigned to arm A (206), arm B (189), and
      arm C (192). BPAR rates were not reduced by rabbit ATG (9.9%) compared with
      either treatment arm A (11.2%) or B (10.6%; A versus C: p=0.75, B versus C
      p=0.87). As a secondary endpoint, rapid steroid withdrawal reduced post
      transplantation diabetes in arm B to 24% and in arm C to 23% compared with 39% in
      control arm A (A versus B and C: p=0.0004). Patient survival (94.7% in arm A,
      97.4% in arm B, and 96.9% in arm C) and censored graft survival (96.1% in arm A,
      96.8% in arm B, and 95.8% in arm C) after 12 months were excellent and equivalent
      in all arms. Safety parameters such as infections or the incidence of post
      transplantation malignancies did not differ between the study arms.
      INTERPRETATION: Rabbit ATG did not show superiority over basiliximab induction
      for the prevention of BPAR after rapid steroid withdrawal within 1 year after
      renal transplantation. Nevertheless, rapid steroid withdrawal after induction
      therapy for patients with a low immunological risk profile can be achieved
      without loss of efficacy and is advantageous in regard to post-transplantation
      diabetes incidence. FUNDING: Investigator Initiated Trial; financial support by
      Astellas Pharma GmbH, Sanofi, and Roche Pharma AG.

PMID- 27871760
TI  - Hepatitis C Treatment: Clinical Issues for Psychiatrists in the Post-Interferon
      Era.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a widespread and costly cause of morbidity
      and mortality globally and in the United States. The treatment of HCV has been
      revolutionized with the recent development of direct-acting antiviral
      medications. These new treatments are substantially better tolerated and more
      efficacious than previously used interferon-based therapies. Despite these
      innovations, sustained virologic response has remained low, hovering at
      approximately 9% of all infected persons. The reasons for this failure include
      lack of screening, low rates of linkage to care, cost of direct-acting
      antivirals, and barriers in access to care for patients. Psychiatrists work with
      patients at a disproportionately high risk for HCV infection yet many do not
      currently assume an active role in the HCV epidemic. OBJECTIVE: The purpose of
      this clinical review is to familiarize psychiatrists with currently available
      hepatitis C treatments and discuss the remaining treatment challenges, including
      the high cost of treatment. METHODS: The authors used information from the
      Centers for Disease Control and Food and Drug Administration on the most current
      estimates of HCV epidemiology, risk factors, and approved interferon-free
      treatments. PUBMED was searched for examples of HCV treatment in community
      psychiatry settings. CONCLUSIONS: The mental health community is well-positioned
      to take on a more active role in HCV treatment and engage patients' trust in the
      treatment process. However, many barriers still exist. We encourage psychiatrists
      to assume a collaborative role in caring for psychiatric patients infected with
      HCV.

PMID- 27871762
TI  - Clinical and Histopathologic Ocular Findings in Disseminated Mycobacterium
      chimaera Infection after Cardiothoracic Surgery.
AB  - PURPOSE: To investigate and characterize clinical and histopathologic ocular
      findings in patients with disseminated infection with Mycobacterium chimaera, a
      slow-growing nontuberculous mycobacterium (NTM), subsequent to cardiothoracic
      surgery. DESIGN: Observational case series. PARTICIPANTS: Five white patients (10
      eyes). METHODS: Analysis of clinical ocular findings, including visual acuity,
      slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD OCT),
      fundus autofluorescence (FAF), and fluorescein angiography/indocyanine green
      (ICG) angiography findings, of patients with a disseminated M. chimaera
      infection. Biomicroscopic and multimodal imaging findings were compared with the
      histopathology of 1 patient. MAIN OUTCOME MEASURES: Clinical and histopathologic
      ocular findings of M. chimaera. RESULTS: The mean age of the 5 male patients,
      diagnosed with endocarditis or aortic graft infection, was 57.8 years. Clinical
      ocular findings included anterior and intermediate uveitis, optic disc swelling,
      and white-yellowish choroidal lesions. Multifocal choroidal lesions were observed
      bilaterally in all patients and were hyperfluorescent on fluorescein angiography,
      hypofluorescent on ICG angiography, and correlated with choroidal lesions on SD
      OCT. The extent of choroidal lesions varied from few in 2 patients to widespread
      miliary lesions in 3 patients leading to localized choroidal thickening with
      elevation of the overlying retinal layers. Spectral-domain optical coherence
      tomography through regressing lesions revealed altered outer retinal layers and
      choroidal hypertransmission. The ocular findings were correlated with the course
      of the systemic disease. Patients with few choroidal lesions had a favorable
      outcome, whereas all patients with widespread chorioretinitis died of systemic
      complications of M. chimaera infection despite long-term targeted antimicrobial
      therapy. Ocular tissue was obtained from 1 patient at autopsy. Necropsy of 2 eyes
      of 1 patient revealed prominent granulomatous lymphohistiocytic choroiditis with
      giant cells. CONCLUSIONS: M. chimaera infection subsequent to cardiothoracic
      surgery is a novel entity that has been recently described. It involves multiple
      organ systems and can cause life-threatening disseminated disease. The ocular
      manifestations documented using multimodal imaging allow us to use the eye as a
      window to the systemic infection.

PMID- 27871764
TI  - The rs4285184 polymorphism of the MGAT1 gene as a risk factor for obesity in the
      Mexican population.
AB  - BACKGROUND AND OBJECTIVE: Obesity is a factor that contributes to the morbidity
      of certain diseases and to worldwide mortality. MGAT1 is a glycosyltransferase
      involved in the synthesis of protein-bound and lipid-bound oligosaccharides and
      its polymorphisms are possibly involved in the etiology of obesity. We
      investigated the association of the rs4285184 polymorphism of the MGAT1 gene with
      obesity in adults in the State of Colima, Mexico. METHODS: A case-control study
      was conducted that included 244 subjects. All of them were grouped according to
      their percentage of body fat, determined through bioelectrical impedance, and
      they were genotyped for the rs4285184 polymorphism of the MGAT1 gene through PCR
      RFLP. The results were analyzed for their association with the percentage of body
      fat. RESULTS: The G allele had a frequency of 49.19 and 38.75% for the cases and
      controls, respectively (P=.020) (OR 1.53; 95% CI 1.068-2.193). The frequency of
      the A/G+G/G genotype was 75% in the obese patients, which was significantly
      higher compared with the 57.5% of the control group (P=.004) (OR 2.217; 95% CI
      1.287-3.821). CONCLUSIONS: The presence of the rs4285184 polymorphism of the
      MGAT1 gene increased the risk for developing body fat associated with obesity in
      the Mexican population.

PMID- 27871763
TI  - Diplopia in Medically and Surgically Treated Patients with Glaucoma.
AB  - PURPOSE: To report the prevalence, type, and cause of diplopia in medically and
      surgically treated patients with glaucoma. DESIGN: Cohort study. PARTICIPANTS: A
      total of 195 adult patients with glaucoma treated in a glaucoma referral
      practice. METHODS: A total of 195 adult patients with glaucoma who had undergone
      surgical or medical management were prospectively enrolled. Forty-seven patients
      had undergone glaucoma drainage device (GDD) surgery (Baerveldt 350, Baerveldt
      250 [Abbott Medical Optics, Abbott Park, IL], or Ahmed FP7 [New World Medical
      Inc, Rancho Cucamonga, CA]), 61 patients had undergone trabeculectomy, and 87
      patients were medically treated. All patients completed the Diplopia
      Questionnaire to assess diplopia. We defined the presence of diplopia as
      "sometimes," "often," or "always" in distance straight ahead or reading positions
      on the Diplopia Questionnaire. A chart review was performed jointly by a
      strabismus specialist and a glaucoma subspecialist to characterize the type and
      cause of the diplopia. MAIN OUTCOME MEASURES: Frequency, type, and cause of
      diplopia. RESULTS: Diplopia was reported in 41 of 195 medically and surgically
      treated patients (21%) with glaucoma. Binocular diplopia due to the glaucoma
      procedure was present in 11 of 47 patients (23%) after GDD (95% confidence
      interval, 12-38), which was significantly greater than in patients after
      trabeculectomy (2/61 [3%]; 95% confidence interval, 0.4-11; P = 0.002). The most
      common type of strabismus associated with binocular diplopia due to glaucoma
      surgery was hypertropia (10/11 GDD cases, 2/2 trabeculectomy cases). Monocular
      diplopia was found in a similar proportion of medically treated, post
      trabeculectomy, and post-GDD cases (4/87 [5%], 4/61 [7%], and 2/47 [4%],
      respectively). Binocular diplopia not due to surgery was found in similar
      proportions of GDD, trabeculectomy, and medically treated cases (3/47 [6%], 5/61
      [8%], and 10/87 [11%], respectively). CONCLUSIONS: Diplopia may be under
      recognized in medically and surgically treated patients with glaucoma, and
      standardization of ascertaining patient symptoms using the Diplopia Questionnaire
      may be useful in these patients. Diplopia was more commonly seen after GDD than
      trabeculectomy, typically a noncomitant restrictive hypertropia. The prevalence
      of monocular diplopia and binocular diplopia unrelated to glaucoma surgery was
      similar among medical and surgical groups. It is important to counsel patients on
      the higher occurrence of diplopia associated with GDD surgery.

PMID- 27871765
TI  - Evaluation of cardiac function in a group of small for gestational age school-age
      children treated with growth hormone.
AB  - INTRODUCTION AND OBJECTIVES: Small for gestational age (SGA) patients have an
      increased risk of developing a cardiovascular pathology, as well as a metabolic
      syndrome. Our objective is to evaluate the cardiac morphology and function of SGA
      children treated with growth hormone (GH), identifying changes that could
      potentially have long-term consequences. METHODS: We selected 23 SGA school-age
      patients and 23 healthy children. We measured their weight, height, blood
      pressure and heart rate. Using transthoracic echocardiography, we evaluated
      cardiac chamber size, ascending and abdominal aortic diameter as well as the
      systolic and diastolic function of both ventricles. RESULTS: SGA children have a
      higher systolic and diastolic blood pressure (P<.05) without significant changes
      in their heart rate. They also have a thicker interventricular septum (SGA Z
      score 1.57 vs. 0.89; P=.026) and a worse right ventricular systolic function,
      with a lower TAPSE (SGA Z-score -0.98 vs. 0.95; P=.000), as well as a lower blood
      flow rate in the pulmonary artery (SGA 0.85m/s vs. 0.97m/s; P=.045). No
      significant difference was observed in the patients' left ventricular function.
      SGA patients' ascending aortic diameter was greater (SGA Z-score -1.09 vs. -1.93;
      P=.026), whereas the systolic abdominal aortic diameter was smaller (SGA Z-score
      0.89 vs. -0.19; P=.015). CONCLUSIONS: We found functional and morphological
      cardiac changes in SGA school-age patients treated with GH. It is important to
      follow-up this patient group in order to determine if these changes contribute to
      an increased cardiac morbidity in adulthood.

PMID- 27871766
TI  - Burning mouth syndrome and associated factors: A case-control retrospective
      study.
AB  - BACKGROUND AND OBJECTIVE: Burning mouth syndrome (BMS) can be defined as burning
      pain or dysesthesia on the tongue and/or other sites of the oral mucosa without a
      causative identifiable lesion. The discomfort is usually of daily recurrence,
      with a higher incidence among people aged 50 to 60 years, affecting mostly the
      female sex and diminishing their quality of life. The aim of this study was to
      evaluate the association between several pathogenic factors and burning mouth
      syndrome. PATIENTS AND METHODS: 736 medical records of patients diagnosed of
      burning mouth syndrome and 132 medical records for the control group were studied
      retrospectively. The study time span was from January 1990 to December 2014. The
      protocol included: sex, age, type of oral discomfort and location, among other
      factors. RESULTS: Analysis of the association between pathogenic factors and BMS
      diagnosis revealed that only 3 factors showed a statistically significant
      association: triggers (P=.003), parafunctional habits (P=.006), and oral hygiene
      (P=.012). There were neither statistically significant differences in BMS
      incidence between sex groups (P=.408) nor association of BMS with the pathogenic
      factors of substance abuse (P=.915), systemic pathology (P=.685), and dietary
      habits (P=.904). CONCLUSIONS: Parafunctional habits like bruxism and abnormal
      movements of tongue and lips can explain the BMS main symptomatology.
      Psychological aspects and systemic factors should be always considered. As a
      multifactorial disorder, the treatment of BMS should be executed in a holistic
      way.

PMID- 27871767
TI  - Nordic walking for cardiovascular prevention in patients with ischaemic heart
      disease or metabolic syndrome.
AB  - BACKGROUND AND OBJECTIVE: The incidence of atherosclerotic diseases has increased
      in Europe due in part to the population's sedentary lifestyle. Physical activity
      is useful for cardiovascular prevention. Nordic walking (NW) mobilizes a great
      number of muscular groups and is very popular in northern Europe. There is no
      data available on its impact in the healthcare system of the Mediterranean area.
      We propose the implementation of a NW program to promote physical activity and
      control cardiovascular risk factors (CVRF), as well as to improve quality of life
      and the adherence to medical treatment in patients with a chronic ischemic heart
      disease or metabolic syndrome. METHODS: We selected patients with uncontrolled
      CVRFs. These patients performed 2 weekly sessions of NW over the course of one
      year. Baseline data extracted from the patients' medical history, quality of life
      questionnaires and on adherence to treatment was compared with the results
      obtained at the end of the program. RESULTS: A reduction in the rate of CVRFs
      from 4.78 to 3 was observed, with an evident trend towards the improvement of the
      patients' quality of life and a better adherence to the treatment. CONCLUSIONS:
      The implementation of a NW program is feasible in the public healthcare system
      and can aid in the management of CVRFs.

PMID- 27871768
TI  - Red cell pyruvate kinase deficiency in Spain: A study of 15 cases.
AB  - BACKGROUND AND OBJECTIVE: Pyruvate kinase deficiency (PKD) is a rare, inherited
      disease causing chronic hemolysis and anemia of varying intensity. The genetic
      heterogeneity of PKD is high and, to this day, over 240 different mutations have
      been identified. PATIENTS AND METHODS: 15 unrelated patients affected by PKD have
      been studied. PKLR gene sequencing was performed by SANGER, including the
      determination of promoter regions, exonic, intronic flanking and 3'UTR. RESULTS:
      Patients were classified into 3 groups based on the intensity of their clinical
      symptoms: I) severe and very severe (8 patients); II) moderate (2 patients), and
      III) mild (5 patients). Six out of the 18 alleles found were new mutations which
      had not been described previously, with the PKLR c.721G>T mutation being the most
      prevalent (26.67%), followed by the PKLR c.1456C>T mutation (13.33%).
      CONCLUSIONS: In Spain, the genetic heterogeneity of PKLR is still high but
      differs from that observed in the previous study carried out in 1998. Total PKLR
      gene sequencing is necessary for the characterization of all patients with PKD
      and for genetic counseling.

PMID- 27871769
TI  - Effect of mechanical vibration on transcutaneous oxygen levels in the feet of
      type 2 diabetes mellitus patients.
AB  - BACKGROUND AND OBJECTIVE: Foot conditions in patients with diabetes mellitus (DM)
      are major causes of morbidity and disability. Whole body vibration may promote
      blood circulation in the lower limbs, hence facilitating perfusion and promoting
      the supply of nutrients and oxygen to comprised tissues. Transcutaneous oxygen
      levels (TcPO2)>40mmHg in cases of diabetic foot syndrome are associated with a
      good prognosis in the resolution of ulcers. The objective of this study was to
      determine whether whole body vibration favors some parameters of interest related
      to complications associated with the diabetic foot syndrome. PATIENTS AND
      METHODS: Fifty-four patients with DM were included in a 12-week exercise program
      based on whole body vibration. Glycemic control was determined on the basis of
      the patients' levels of glycated hemoglobin (HbA1c); sensitivity and TcPO2 levels
      of each foot were also recorded. Assessments were performed prior to initiating
      the whole body vibration program and at the end of it. RESULTS: No significant
      changes were observed in the patients' HbA1c (P=.442) levels or sensitivity
      (P=.07). A significant 7mmHg increase (P<.0001; effect size: d=0.53) was observed
      in the concentration of TcPO2. CONCLUSIONS: Whole body vibration may increase
      TcPO2 levels with useful implications for the prevention or management of
      complications associated with restricted blood perfusion in the diabetic foot
      syndrome.

PMID- 27871770
TI  - PTSD in those who care for the injured.
AB  - BACKGROUND: Post Traumatic Stress Disorder (PTSD) has become a focus for the care
      of trauma victims, but the incidence of PTSD in those who care for injured
      patients has not been well studied. Our hypothesis was that a significant
      proportion of health care providers involved with trauma care are at risk of
      developing PTSD. METHODS: A system-wide survey was applied using a modified
      version of the Primary Care PTSD Screen [PC-PTSD], a validated PTSD screening
      tool currently being used by the VA to screen veterans for PTSD. Pre-hospital and
      in-hospital care providers including paramedics, nurses, trauma surgeons,
      emergency medicine physicians, and residents were invited to participate in the
      survey. The survey questionnaire was anonymously and voluntarily performed online
      using the Qualtrix system. Providers screened positive if they affirmatively
      answered any three or more of the four screening questions and negative if they
      answered less than three questions with a positive answer. Respondents were
      grouped by age, gender, region, and profession. RESULTS: 546 providers answered
      all of the survey questions. The screening was positive in 180 (33%) and negative
      in 366 (67%) of the responders. There were no differences observed in screen
      positivity for gender, region, or age. Pre-hospital providers were significantly
      more likely to screen positive for PTSD compared to the in-hospital providers
      (42% vs. 21%, P<0.001). Only 55% of respondents had ever received any information
      or education about PTSD and only 13% of respondents ever sought treatment for
      PTSD. CONCLUSION: The results of this survey are alarming, with high proportions
      of healthcare workers at risk for PTSD across all professional groups. PTSD is a
      vastly underreported entity in those who care for the injured and could
      potentially represent a major problem for both pre-hospital and in-hospital
      providers. A larger, national study is warranted to verify these regional
      results.

PMID- 27871771
TI  - Characteristics of erythrocyte-derived microvesicles and its relation with
      atherosclerosis.
AB  - Microvesicles are formed under many circumstances, especially in atheromatous
      plaques. Erythrocyte-derived microvesicles (ErMVs) have been proved to promote
      atherosclerosis by promoting hypercoagulation, mediating inflammation and
      inducing cell adhesion. Several clinical studies have reported potential roles of
      ErMVs in cardiovascular disease diagnosis, but the current understanding of ErMVs
      remains insufficient. In this paper, we will review current research on the
      formation and degradation of ErMVs and the possible effects of ErMVs in
      atherosclerosis, discuss potential clinical applications in cardiovascular
      disease, and hope to raise awareness of the relation with atherosclerosis.

PMID- 27871772
TI  - Identifying play characteristics of pre-school children with developmental
      coordination disorder via parental questionnaires.
AB  - : Motor coordination deficits that characterize children with Developmental
      Coordination Disorder (DCD) affect their quality of participation. The aim of the
      current study was to identify play characteristics of young children with DCD,
      compared to those of children with typical development in three dimensions:
      activity and participation, environmental factors and children's impairments.
      METHOD: Sixty-four children, aged four to six years, participated. Thirty were
      diagnosed as having DCD; the remaining 34 children were age, gender and
      socioeconomic level matched controls with typical development. The children were
      evaluated by the M-ABC. In addition, their parents completed a demographic
      questionnaire, the Children's Activity Scale for Parents (CHAS-P), the Children's
      Leisure Assessment Scale for preschoolers (CLASS-Pre), and My Child's Play
      Questionnaire (MCP). RESULTS: Children with DCD performed significantly poorer in
      each of the four play activity and participation domains: variety, frequency,
      sociability, and preference (CLASS-Pre). Furthermore, their environmental
      characteristics were significantly different (MCP). They displayed significantly
      inferior performance (impairments) in interpersonal interaction and executive
      functioning during play, in comparison to controls (MCP). Moreover, the
      children's motor and executive control as reflected in their daily function as
      well as their activities of daily living (ADL) performance level, contributed to
      the prediction of their global play participation. DISCUSSION: The results
      indicate that the use of both the CLASS-Pre and the MCP questionnaires enables
      the identification of unique play characteristics of pre-school children with DCD
      via parents' reports. A better insight into these characteristics may contribute
      to theoretical knowledge and clinical practice to improve the children's daily
      participation.

PMID- 27871774
TI  - Bias to Basis.

PMID- 27871773
TI  - Generally Regarded As Safe.

PMID- 27871775
TI  - Recombinant proteins of helminths with immunoregulatory properties and their
      possible therapeutic use.
AB  - The inverse relationship between helminth infections and the development of
      immune-mediated diseases is a cornerstone of the hygiene hypothesis and studies
      were carried out to elucidate the mechanisms by which helminth-derived molecules
      can suppress immunological disorders. These studies have fostered the idea that
      parasitic worms may be used as a promising therapeutic alternative for prevention
      and treatment of immune-mediated diseases. We discuss the current approaches for
      identification of helminth proteins with potential immunoregulatory properties,
      including the strategies based on high-throughput technologies. We also explore
      the methodological approaches and expression systems used for production of the
      recombinant forms of more than 20 helminth immunomodulatory proteins, besides
      their performances when evaluated as immunotherapeutic molecules to treat
      different immune-mediated conditions, including asthma and inflammatory bowel
      diseases. Finally, we discuss the perspectives of using these parasite-derived
      recombinant molecules as tools for future immunotherapy and immunoprophylaxis of
      human inflammatory diseases.

PMID- 27871776
TI  - Life cycle of Spinose ear tick, Otobius megnini (Acari: Argasidae) infesting the
      race horses in Nuwara Eliya, Sri Lanka.
AB  - Otobius megnini infests mainly domesticated and wild animals and occasionally
      humans. It has been identified as an agent of human and horse otoacariasis in Sri
      Lanka. The number of nymphal stages in the life cycle of O. megnini varies from
      one to three in different geographic regions. The present study determined the
      life cycle of O. megnini infesting the racehorses in Nuwara Eliya. A tick colony
      was initiated from fully engorged nymphs collected from horses and maintained at
      10 degrees C, 22 degrees C and 28 degrees C. Immature stages were reared on New
      Zealand rabbits. Only the larvae weighing more than 0.9mg (84.9%) moulted to
      nymphs with a pre-moulting period of 5.6(+/-1.7) days. None of the larvae
      maintained at 10+/-1 degrees C moulted. Larval survival was significantly higher
      at 28+/-1 degrees C (44.2+/-4.3days) than at 22+/-1 degrees C (35.6+/-9days). At
      28+/-1 degrees C, majority of nymphs (95.6%) weighing over 10mg moulted into
      adults within 12.5(+/-3.1) days. Nymphs kept at 10+/-1 degrees C underwent
      diapause for 81.1(+/-72.0) days. Larger females (>13mg; 93.0%) laid eggs for of
      44.6(+/-17.8) days with a mean pre-oviposition period of 10.3(+/-5.1) days.
      Females survived longer (369.8+/-128.3days) than males (210.4+/-54.1days;
      Student's t-test; t=5.9, p=0.001). Some females laid eggs without mating. Otobius
      megnini successfully completed the life cycle within 123days and has only one
      nymphal instar similar to the Neotropical population. Currently, O. megnini
      infestation is a serious problem to horses in the Nuwara Eliya racecourse and may
      pose a risk of spreading to dairy farms close by owing to its dynamic nature of
      the life cycle.

PMID- 27871777
TI  - Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel
      Therapeutics.
AB  - Precision medicine continues to be the benchmark to which we strive in cancer
      research. Seeking out actionable aberrations that can be selectively targeted by
      drug compounds promises to optimize treatment efficacy and minimize toxicity.
      Utilizing these different targeted agents in combination or in sequence may
      further delay resistance to treatments and prolong antitumor responses.
      Remarkable progress in the field of immunotherapy adds another layer of
      complexity to the management of cancer patients. Corresponding advances in
      companion biomarker development, novel methods of serial tumor assessments, and
      innovative trial designs act synergistically to further precision medicine.
      Ongoing hurdles such as clonal evolution, intra- and intertumor heterogeneity,
      and varied mechanisms of drug resistance continue to be challenges to overcome.
      Large-scale data-sharing and collaborative networks using next-generation
      sequencing (NGS) platforms promise to take us further into the cancer 'ome' than
      ever before, with the goal of achieving successful precision medicine.

PMID- 27871778
TI  - [Traumatic submacular hemorrhage treated by intravitreal rt-PA injection and core
      vitrectomy in an 18-year-old man].

PMID- 27871779
TI  - Intraocular pressure measurement after DSAEK by iCare, Goldmann applanation and
      dynamic contour tonometry: A comparative study.
AB  - PURPOSE: Corneal thickness inevitably increases following Descemet's stripping
      automated endothelial keratoplasty (DSAEK), owing to the addition of a donor
      graft. The current study compares different devices in assessing post-DSAEK
      intraocular pressure (IOP). METHODS: We compared IOP values measured by the
      Goldmann tonometry (GAT), iCare rebound tonometry (iCare) and Pascal dynamic
      contour tonometry (PDCT) in eyes following DSAEK. Agreement between measurements
      was calculated with correlation analysis and Bland-Altman plots. Effects of
      keratometry, central, thickness (CCT), endothelial cell density (ECD) and axial
      length on IOP measurements were assessed with Pearson's correlation. RESULTS:
      Twenty eyes of 20 patients (mean age 74.3+/-14.4, 14 females) post-DSAEK were
      included in this study. There was a high concordance between the IOP readings
      obtained by the three devices: a strong and significant correlation was found
      between GAT and PDCT (r=0.94, P<0.001) GAT and iCare (r=0.86, P<0.001) and iCare
      with PDCT (r=0.81, P<0.001). However, the iCare measurements were significantly
      and consistently lower than that obtained with GAT (DeltaIOP=1.68+/-2.0, P=0.002,
      95% CI: 0.7-2.6) and with PDCT (DeltaIOP=1.61+/-2.5, P=0.01, 95% CI: 0.4-2.8).
      CCT, ECD, CCT, AXL, corneal curvature or astigmatism did not influence IOP
      measurement by any instrument. CONCLUSIONS: IOP measurement with three different
      techniques (applanation, rebound and dynamic contour) showed good correlations,
      despite an increased corneal thickness following DSAEK. However, the iCare, which
      is based on a rebound tonometry showed significant lower IOP then the two other
      methods. This should be taken into account when evaluating patients post DSAEK.

PMID- 27871780
TI  - Type 2 Diabetes, Hypoglycemia, and Basal Insulins: Ongoing Challenges.
AB  - Hypoglycemia in people with insulin-treated type 2 diabetes can be a limiting
      factor for management and a barrier to optimizing glycemic control. Even mild
      episodes of hypoglycemia can affect an individual's quality of life, and fear of
      hypoglycemia can lead to underinsulinization. This article explores the
      prevalence and consequences of hypoglycemia in people with type 2 diabetes with a
      focus on those who use basal insulins, offering strategies for prevention and
      management. It also discusses the benefits and challenges associated with new
      basal insulins, and their potential role in reducing hypoglycemia risk.

PMID- 27871781
TI  - Crocin inhibits RANKL-induced osteoclast formation and bone resorption by
      suppressing NF-kappaB signaling pathway activation.
AB  - Crocin is a dietary compound with antioxidant and anti-inflammatory properties,
      but its effects on bone resorption have not been well characterized. Here we
      address this issue by examining the direct effects of crocin on osteoclast cells
      in vitro. Osteoclastogenesis was induced by RANKL (receptor activator of NF
      kappaB ligand) in mouse bone marrow-derived macrophages in the absence or
      presence of crocin at various concentrations. Further, the bone resorption
      activity of mature osteoclast treated with crocin was assessed by pit assay.
      Without altering cell viability, crocin was shown to inhibit the differentiation
      and function of osteoclast cells in a dose-dependent manner. Mechanistically,
      RANKL-induced NF-kappaB and NFATc1 activation, the critical signaling pathways
      for osteoclast differentiation and function, were both repressed by crocin in
      bone marrow-derived macrophages. Thus, crocin suppresses osteoclastogenesis
      through direct inhibition of intracellular molecular pathways, which may
      contribute to future development of anti-bone resorption treatment.

PMID- 27871782
TI  - Association of high HLA-E expression during acute cellular rejection and numbers
      of HLA class I leader peptide mismatches with reduced renal allograft survival.
AB  - Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader
      peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed
      immune responses by interacting with inhibitory NKG2A or by activating NKG2C
      receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft
      survival during acute cellular rejection. HLA-E expression was up-regulated in
      acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal
      allografts with no rejection-signs. HLA-E up-regulation was correlated with
      numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+
      infiltrating cells correlated with HLA-E expression (p<0.0001 and p=0.0009,
      respectively). Activating NKG2C receptor dominated on effector cells in biopsies
      and peripheral blood during ACR potentially allowing HLA-E-mediated immune
      activation. Moreover, HLA-E expression correlated with deterioration in renal
      allograft function (p<0.008) and reduced allograft survival (p=0.002). Our
      findings provide evidence that during renal allograft rejection HLA-E along with
      high numbers of mismatched HLA-class I leader peptides might represent additional
      targets for immune-activating responses.

PMID- 27871783
TI  - Human Dental Pulp Stem Cells Suppress Alloantigen-induced Immunity by Stimulating
      T Cells to Release Transforming Growth Factor Beta.
AB  - INTRODUCTION: Human dental pulp stem cells (hDPSCs) are ideal candidates for
      regenerating damaged dental tissue. To examine the possibility that hDPSCs may be
      used to regenerate pulp, we tested their in vitro effects on acute allogeneic
      immune responses. METHODS: A peripheral blood mononuclear cell (PBMC)
      proliferation assay and immunoglobulin (Ig) production assay were performed to
      evaluate the immunosuppressive properties of hDPSCs. RESULTS: The mixed
      lymphocyte reaction was suppressed by incubation with hDPSCs. Transforming growth
      factor beta (TGF-beta) was the major soluble factor responsible for inhibiting
      the allogeneic proliferation of PBMCs. The production of IgM and IgG by
      allogeneic activation of responder B lymphocytes was also completely abrogated by
      TGF-beta released from hDPSCs via interferon gamma in response to activation of
      the responder T lymphocytes. CONCLUSIONS: hDPSCs inhibit acute allogeneic immune
      responses by their release of TGF-beta as a result of allogeneic stimulation of T
      lymphocytes. This study provides an insight into the potential clinical use of
      hDPSCs for allogeneic transplantation.

PMID- 27871784
TI  - Reply to the letter to editor "Impact of epicardial adipose tissue volume
      quantified by non-contrast electrocardiogram-gated computed tomography on
      ergonovine-induced epicardial coronary artery spasm".

PMID- 27871785
TI  - Hyperuricemia is an independent competing risk factor for atrial fibrillation.
AB  - BACKGROUNDS: The relationship between serum uric acid (SUA) and atrial
      fibrillation (AF) remains unclear because many parameters and diseases influence
      AF. This study was conducted to clarify the role of hyperuricemia as an
      independent competing risk factor for AF in an apparently healthy general
      population. METHODS: We retrospectively analyzed the medical records of 90,143
      Japanese subjects who underwent annual regular health check-up in St. Luke's
      International Hospital, Tokyo, between January 2004 and June 2010. Of those
      subjects, 291 (0.32%) were identified as having AF by 12 leads
      electrocardiography. First, we analyzed 90,117 subjects to clarify the
      independent competing risk factors for AF and obtained odds ratios (ORs) by
      logistic regression analysis. Second, we excluded 40,825 subjects with
      hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, and
      current medication for hyperuricemia and/or gout, and we analyzed 49,292
      subjects. RESULTS: First, AF groups were significantly higher SUA level (OR:
      1.35; 95% confidence interval (CI), 1.22-1.50) than non-AF group. OR of
      hyperuricemia (>7.0mg/dL of SUA) for AF was 2.75 (95% CI, 2.10-3.60). Second,
      after multiple adjustments, higher SUA level (OR: 1.53; 95% CI, 1.21-1.92) was a
      significantly independent competing risk factor for AF, as well as older age,
      male sex, higher body mass index, lower FEV1/FVC, and higher hemoglobin. OR of
      hyperuricemia for AF was 3.19 (95% CI, 1.81-5.62). CONCLUSIONS: Hyperuricemia is
      an independent competing risk factor for AF. Further prospective intervention
      studies are needed to prove whether lowering SUA level might be important for
      preventing AF or not.

PMID- 27871786
TI  - Ischemic brain infarcts and intracranial haemorrhages following Russell's viper
      (Daboia russelii) bite in Sri Lanka.
AB  - Snakebite is an important medical problem in Sri Lanka. Of the deadly venomous
      snakes, Russell's viper (Daboia russelii) is widely distributed and responsible
      for most of the fatalities of snakebite in the country. It is not uncommon to see
      atypical manifestations in Russell's viper bite. We report the events of
      intracranial haemorrhages and multiple ischemic brain infarcts following
      Russell's viper (Daboia russelii) bite of a previously healthy 43-years-old male
      who succumbed to envenoming.

PMID- 27871788
TI  - Do monkeys have a theory of mind? How to answer the question?
AB  - Since Premack and Woodruf (1978), the study of mindreading abilities in
      nonhumans, especially primates, has been thoroughly investigated. But attempts to
      understand the evolution of this aspect of human intelligence have mainly focused
      on comparisons between apes and human infants, while relatively little is known
      about the abilities of monkeys. This lack of data on monkeys seems mainly due to
      the hypothesis of a cognitive "gap" between apes and monkeys. However, in recent
      years monkeys have been featuring more prominently in the landscape of social
      cognition research, and some of these systematic studies appear promising. This
      paper reviews i) current knowledge about monkeys' socio-cognitive abilities,
      especially regarding gaze processing, attention and intention reading, and
      perspective-taking, ii) alternative hypotheses regarding the underlying
      mechanisms of such complex behaviors, and iii) potential new perspectives and
      future directions for studying ToM in monkeys.

PMID- 27871787
TI  - Selfish brain and selfish immune system interplay: A theoretical framework for
      metabolic comorbidities of mood disorders.
AB  - According to the "selfish brain" theory, the brain regulates its own energy
      supply influencing the peripheral metabolism and food intake according to its
      needs. The immune system has been likewise "selfish" due to independent energy
      consumption; and it may compete with the brain (another high energy-consumer) for
      glucose. In mood disorders, stress in mood episodes or physiological stress
      activate homeostasis mechanisms from the brain and the immune system to solve the
      imbalance. The interaction between the selfish brain and the selfish immune
      system may explain various conditions of medical impairment in mood disorders,
      such as Metabolic Syndrome (MetS), obesity, type 2 diabetes mellitus (T2DM) and
      immune dysregulation. The objective of this study is to comprehensively review
      the literature regarding the competition between the brain and the immune system
      for energy substrate. Targeting the energetic regulation of the brain and the
      immune system and their cross-talk open alternative treatments and a different
      approach in the study of general medical comorbidities in mood disorders,
      although more investigation is needed.

PMID- 27871789
TI  - Effect of dry heating and ionic gum on the physicochemical and release properties
      of starch from Dioscorea.
AB  - To meet the ever increasing industrial demand for excipients with desirable
      properties, modified starch is regarded as an alternative to it. With this in
      mind, the present study focuses on the modification of starches of Dioscorea from
      Jharkhand (India) using dry heat treatment with and without ionic gum. Modified
      starches were prepared using sodium alginate (1% w/w). Native and modified
      starches were subjected to heat treatment at 130 degrees C for 2h and 4h. The
      effect of heating and ionic gum on the properties of Dioscorea starch was
      investigated. The amylose content, water holding capacity, micromeritic
      properties, swelling power, solubility and morphology of starches were evaluated.
      Dry heat treatment of starches without gum showed an increment in water-holding
      capacity after two-hours heating, but no such increment was found after four
      hours heating. Oil binding capacity of starches modified with gum varied from 62%
      to 78%. Strongest effect of heat treatment occurred on the morphology of starches
      and thereby modified starches showed distorted surface morphology. Amylose
      content (21.09-21.89%) found to be decreased with the addition of gum which lead
      to decrease in paste clarity. Starches heated with gum at high-temperature
      resulted in restrict swelling and slight increase in solubility. Micromeritic
      properties of the modified starches showed the good flow properties. Further, the
      modified starches were investigated for in-vitro release studies and that the
      thermally modified derivatives can be a good prospect in slow release
      formulations.

PMID- 27871791
TI  - WhmD promotes the assembly of Mycobacterium smegmatis FtsZ: A possible role of
      WhmD in bacterial cell division.
AB  - WhmD is considered to have a role in the septation and division of Mycobacterium
      smegmatis cells. Since FtsZ is the central protein of the septum, we determined
      the effect of WhmD on the assembly of Mycobacterium smegmatis FtsZ (MsFtsZ) in
      vitro. WhmD increased both the rate and extent of the assembly of MsFtsZ in
      vitro. WhmD also increased the amount of polymerized MsFtsZ as evident from a
      sedimentation assay. Further, the assembly promoting activity of WhmD occurred in
      the presence of GTP. MsFtsZ polymerized to form thin filaments in the absence of
      WhmD while MsFtsZ formed thick filaments in the presence of WhmD suggesting that
      WhmD enhanced the bundling of MsFtsZ filaments. Interestingly, WhmD neither
      suppressed the dilution-induced disassembly of FtsZ filaments nor significantly
      altered the GTPase activity of FtsZ. Using size exclusion chromatography,
      circular dichroism and fluorescence spectroscopy, WhmD was found to bind to
      MsFtsZ in vitro. The results showed that WhmD can promote the assembly of FtsZ
      and indicated that WhmD may play a role in the division of M. smegmatis cells by
      assisting the polymerization of FtsZ.

PMID- 27871790
TI  - Antioxidant and anti-hyperlipidemic effects of mycelia zinc polysaccharides by
      Pleurotus eryngii var. tuoliensis.
AB  - The aims of this work were designed to investigate the hepatoprotective and
      antioxidant effects of acidic- and alkali-extractable mycelia zinc
      polysaccharides (AcMZPS, AlMZPS) from Pleurotus eryngii var. tuoliensis on high
      fat-high-cholesterol emulsion-induced hyperlipidemic mice. The in vivo
      experiments demonstrated that both AcMZPS and AlMZPS had potential
      hepatoprotective effects by significantly decreasing the levels of LDL-C, VLDL-C,
      TC, TG, ALT, AST, ALP, MDA and LPO, and remarkably increasing the HDL-C, SOD, GSH
      Px, and CAT in serum lipid/liver homogenate, respectively. In addition, four
      polysaccharide fractions of AcMZPS-1, AcMZPS-2, AlMZPS-1, and AlMZPS-2, purified
      from AcMZPS and AlMZPS using DEAE chromatography, respectively, were subjected to
      monosaccharide composition analysis and valuated for the in vitro antioxidant
      activity. The results obtained in present study suggested that AcMZPS, AlMZPS and
      their purified fractions could be used as functional foods and natural drugs in
      preventing the hyperlipidemia and non-alcoholic fatty liver.

PMID- 27871792
TI  - Dual inhibition of BACE1 and Abeta aggregation by beta-ecdysone: Application of a
      phytoecdysteroid scaffold in Alzheimer's disease therapeutics.
AB  - Current medications for the complex neurological disorder, Alzheimer's disease
      (AD), can neither stop disease progression nor revert back disease pathogenesis.
      The present study demonstrates the applicability of a phytoecdysteroid, beta
      ecdysone, as a multi-potent agent in AD therapeutics. beta-ecdysone strongly
      binds to the active site cavity of BACE1 with calculated dissociation constant of
      1.75+/-0.1MUM. Steady-state and time-resolved fluorescence spectroscopy reveal
      that binding of beta-ecdysone induces conformational transition of the protein
      from open to closed form thereby blocking substrate binding. Even 500nM of the
      compound completely blocks the enzyme activity. Furthermore, beta-ecdysone
      strongly inhibits Abeta aggregation, evident from ANS and ThT binding assay. Co
      incubation of equimolar peptide and beta-ecdysone completely inhibits Abeta
      fibril formation which is further complemented by the AFM study. Low systemic
      toxicity of beta-ecdysone further extends the applicability of the compound as
      functional food and dietary supplement for disease management.

PMID- 27871793
TI  - Combining in silico and in vitro approaches to evaluate the acetylcholinesterase
      inhibitory profile of some commercially available flavonoids in the management of
      Alzheimer's disease.
AB  - The current objective of the study is to identify inhibitory affinity potential
      of the certain commercially available flavonoids, against crystal structure of
      acetylcholinesterase (AChE) enzyme using in silico and in vitro studies. The
      inhibitory profiles of the compounds have been compared with standard AChE
      inhibitor donepezil. In the docking studies, conformational site analysis and
      docking parameters like binding energy, inhibition constant and intermolecular
      energy were determined using AutoDock 4.2. Docking studies conducted with
      diosmin, silibinin, scopoletin, taxifolin and tricetin exhibited tight binding
      forces prevailing with the enzyme than between donepezil. Based on the in silico
      studies, compounds were selected for the in vitro AChE inhibitory assay. In vitro
      results showed that all the selected flavonoids displayed excellent concentration
      dependant inhibition of AChE. Scopoletin was found to be the most potent and
      specific inhibitor of the enzyme with IC50 values of 10.18+/-0.68MUM. Scopoletin
      showed several strong hydrogen bonds to several important amino acid residues
      against target enzyme. A number of hydrophobic interactions could also explain
      the potency of the compounds to inhibit AChE. These molecular docking and in
      vitro analyses could lead to the further development of potent
      acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.

PMID- 27871794
TI  - Accessory subunit NUYM (NDUFS4) is required for stability of the electron input
      module and activity of mitochondrial complex I.
AB  - Mitochondrial complex I is an intricate 1MDa membrane protein complex with a
      central role in aerobic energy metabolism. The minimal form of complex I consists
      of fourteen central subunits that are conserved from bacteria to man. In
      addition, eukaryotic complex I comprises some 30 accessory subunits of largely
      unknown function. The gene for the accessory NDUFS4 subunit of human complex I is
      a hot spot for fatal pathogenic mutations in humans. We have deleted the gene for
      the orthologous NUYM subunit in the aerobic yeast Yarrowia lipolytica, an
      established model system to study eukaryotic complex I and complex I linked
      diseases. We observed assembly of complex I which lacked only subunit NUYM and
      retained weak interaction with assembly factor N7BML (human NDUFAF2). Absence of
      NUYM caused distortion of iron sulfur clusters of the electron input domain
      leading to decreased complex I activity and increased release of reactive oxygen
      species. We conclude that NUYM has an important stabilizing function for the
      electron input module of complex I and is essential for proper complex I
      function.

PMID- 27871795
TI  - Reaction of S. cerevisiae mitochondria with ligands: Kinetics of CO and O2
      binding to flavohemoglobin and cytochrome c oxidase.
AB  - Kinetic methods used to investigate electron and proton transfer within
      cytochrome c oxidase (CytcO) are often based on the use of light to dissociate
      small ligands, such as CO, thereby initiating the reaction. Studies of intact
      mitochondria using these methods require identification of proteins that may bind
      CO and determination of the ligand-binding kinetics. In the present study we have
      investigated the kinetics of CO-ligand binding to S. cerevisiae mitochondria and
      cellular extracts. The data indicate that CO binds to two proteins, CytcO and a
      (yeast) flavohemoglobin (yHb). The latter has been shown previously to reside in
      both the cell cytosol and the mitochondrial matrix. Here, we found that yHb
      resides also in the intermembrane space and binds CO in its reduced state. As
      observed previously, we found that the yHb population in the mitochondrial matrix
      binds CO, but only after removal of the inner membrane. The mitochondrial yHb (in
      both the intermembrane space and the matrix) recombines with CO with tau?270ms,
      which is significantly slower than observed with the cytosolic yHb (main
      component tau?1.3ms). The data indicate that the yHb populations in the different
      cell compartments differ in structure.

PMID- 27871797
TI  - Direct PCR - A rapid method for multiplexed detection of different serotypes of
      Salmonella in enriched pork meat samples.
AB  - Salmonellosis, an infectious disease caused by Salmonella spp., is one of the
      most common foodborne diseases. Isolation and identification of Salmonella by
      conventional bacterial culture method is time consuming. In response to the
      demand for rapid on line or at site detection of pathogens, in this study, we
      developed a multiplex Direct PCR method for rapid detection of different
      Salmonella serotypes directly from pork meat samples without any DNA purification
      steps. An inhibitor-resistant Phusion Pfu DNA polymerase was used to overcome PCR
      inhibition. Four pairs of primers including a pair of newly designed primers
      targeting Salmonella spp. at subtype level were incorporated in the multiplex
      Direct PCR. To maximize the efficiency of the Direct PCR, the ratio between
      sample and dilution buffer was optimized. The sensitivity and specificity of the
      multiplex Direct PCR were tested using naturally contaminated pork meat samples
      for detecting and subtyping of Salmonella spp. Conventional bacterial culture
      methods were used as reference to evaluate the performance of the multiplex
      Direct PCR. Relative accuracy, sensitivity and specificity of 98.8%; 97.6% and
      100%, respectively, were achieved by the method. Application of the multiplex
      Direct PCR to detect Salmonella in pork meat at slaughter reduces the time of
      detection from 5 to 6 days by conventional bacterial culture and serotyping
      methods to 14 h (including 12 h enrichment time). Furthermore, the method poses a
      possibility of miniaturization and integration into a point-of-need Lab-on-a-chip
      system for rapid online pathogen detection.

PMID- 27871796
TI  - Diversity of bat astroviruses in Lao PDR and Cambodia.
AB  - Astroviruses are known to infect humans and a wide range of animal species, and
      can cause gastroenteritis in their hosts. Recent studies have reported
      astroviruses in bats in Europe and in several locations in China. We sampled 1876
      bats from 17 genera at 45 sites from 14 and 13 provinces in Cambodia and Lao PDR
      respectively, and tested them for astroviruses. Our study revealed a high
      diversity of astroviruses among various Yangochiroptera and Yinpterochiroptera
      bats. Evidence for varying degrees of host restriction for astroviruses in bats
      was found. Furthermore, additional Pteropodid hosts were detected. The
      astroviruses formed distinct phylogenetic clusters within the genus
      Mamastrovirus, most closely related to other known bat astroviruses. The
      astrovirus sequences were found to be highly saturated indicating that
      phylogenetic relationships should be interpreted carefully. An astrovirus
      clustering in a group with other viruses from diverse hosts, including from
      ungulates and porcupines, was found in a Rousettus bat. These findings suggest
      that diverse astroviruses can be found in many species of mammals, including
      bats.

PMID- 27871798
TI  - The association of air pollution and greenness with mortality and life expectancy
      in Spain: A small-area study.
AB  - BACKGROUND: Air pollution exposure has been associated with an increase in
      mortality rates, but few studies have focused on life expectancy, and most
      studies had restricted spatial coverage. A limited body of evidence is also
      suggestive for a beneficial association between residential exposure to greenness
      and mortality, but the evidence for such an association with life expectancy is
      still very scarce. OBJECTIVE: To investigate the association of exposure to air
      pollution and greenness with mortality and life expectancy in Spain. METHODS:
      Mortality data from 2148 small areas (average population of 20,750 inhabitants,
      and median population of 7672 inhabitants) covering Spain for years 2009-2013
      were obtained. Average annual levels of PM10, PM2.5, NO2 and O3 were derived from
      an air quality forecasting system at 4*4km resolution. The normalized difference
      vegetation index (NDVI) was used to assess greenness in each small area. Air
      pollution and greenness were linked to standardized mortality rates (SMRs) using
      Poisson regression and to life expectancy using linear regression. The models
      were adjusted for socioeconomic status and lung cancer mortality rates (as a
      proxy for smoking), and accounted for spatial autocorrelation. RESULTS: The
      increase of 5MUg/m3 in PM10, NO2 and O3 or of 2MUg/m3 in PM2.5 concentration
      resulted in a loss of life in years of 0.90 (95% credibility interval CI: 0.83,
      0.98), 0.13 (95% CI: 0.09, 0.17), 0.20years (95% CI: 0.16, 0.24) and 0.64 (0.59,
      0.70), respectively. Similar associations were found in the SMR analysis, with
      stronger associations for PM2.5 and PM10, which were associated with an increased
      mortality risk of 3.7% (95% CI: 3.5%, 4.0%) and 5.7% (95% CI: 5.4%, 6.1%). For
      greenness, a protective effect on mortality and longer life expectancy was only
      found in areas with lower socioeconomic status. CONCLUSIONS: Air pollution
      concentrations were associated to important reductions in life expectancy. The
      reduction of air pollution should be a priority for public health.

PMID- 27871799
TI  - Molecular mechanisms of PFOA-induced toxicity in animals and humans: Implications
      for health risks.
AB  - As an emerging persistent organic pollutant (POP), perfluorooctanoate (PFOA) is
      one of the most abundant perfluorinated compounds (PFCs) in the environment. This
      review summarized the molecular mechanisms and signaling pathways of PFOA-induced
      toxicity in animals and humans as well as their implications for health risks in
      humans. Traditional PFOA-induced signal pathways such as peroxisome proliferating
      receptor alpha (PPARalpha), constitutive androstane receptor (CAR), farnesoid X
      receptor (FXR), and pregnane-X receptor (PXR) may not be important for PFOA
      induced health effects on humans. Instead, pathways including p53/mitochondrial
      pathway, nuclear lipid hyperaccumulation, phosphatidylinositol 3-kinase
      serine/threonine protein kinase (PI3K-AKT), and tumor necrosis factor
      alpha/nuclear factor kappaB (TNF-alpha/NF-kappaB) may play an important role for
      PFOA-induced health risks in humans. Both in vivo and in vitro studies are needed
      to better understand the PFOA-induced toxicity mechanisms as well as the
      associated health risk in humans.

PMID- 27871800
TI  - Zymosan-induced immune challenge modifies the stress response of hypoxic air
      breathing fish (Anabas testudineus Bloch): Evidence for reversed patterns of
      cortisol and thyroid hormone interaction, differential ion transporter functions
      and non-specific immune response.
AB  - Fishes have evolved physiological mechanisms to exhibit stress response, where
      hormonal signals interact with an array of ion transporters and regulate
      homeostasis. As major ion transport regulators in fish, cortisol and thyroid
      hormones have been shown to interact and fine-tune the stress response. Likewise,
      in fishes many interactions have been identified between stress and immune
      components, but the physiological basis of such interaction has not yet
      delineated particularly in air-breathing fish. We, therefore, investigated the
      responses of thyroid hormones and cortisol, ion transporter functions and non
      specific immune response of an obligate air-breathing fish Anabas testudineus
      Bloch to zymosan treatment or hypoxia stress or both, to understand how immune
      challenge modifies the pattern of stress response in this fish. Induction of
      experimental peritonitis in these fish by zymosan treatment (200ngg-1) for 24h
      produced rise in respiratory burst and lysozomal activities in head kidney
      phagocytes. In contrast, hypoxia stress for 30min in immune-challenged fish
      reversed these non-specific responses of head kidney phagocytes. The decline in
      plasma cortisol in zymosan-treated fish and its further suppression by hypoxia
      stress indicate that immune challenge suppresses the cortisol-driven stress
      response of this fish. Likewise, the decline in plasma T3 and T4 after zymosan
      treatment and the rise in plasma T4 after hypoxia stress in immune-challenged
      fish indicate a critical role for thyroid hormone in immune-stress response due
      to its differential sensitivity to both immune and stress challenges. Further,
      analysis of the activity pattern of ion-dependent ATPases viz. Na+/K+-ATPase,
      H+/K+-ATPase and Na+/NH4+-ATPase indicates a functional interaction of ion
      transport system with the immune response as evident in its differential and
      spatial modifications after hypoxia stress in immune-challenged fish. The immune
      challenge that produced differential pattern of mRNA expression of Na+/K+-ATPase
      alpha-subunit isoforms; nkaalpha1a, nkaalpha1b and nkaalpha1c and the shift in
      nkaalpha1a and nkaalpha1b isoforms expression after hypoxia stress in immune
      challenged fish, presents transcriptomic evidence for a modified Na+/K+ ion
      transporter system in these fish. Collectively, our data thus provide evidence
      for an interactive immune-stress response in an air-breathing fish, where the
      patterns of cortisol-thyroid hormone interaction, the ion transporter functions
      and the non-specific immune responses are reversed by hypoxia stress in immune
      challenged fish.

PMID- 27871803
TI  - Abdominal drainage versus no abdominal drainage for laparoscopic cholecystectomy:
      A systematic review with meta-analysis and trial sequential analysis.
AB  - The aim is to assess the benefits and harms of routine abdominal drainage in
      laparoscopic cholecystectomy. We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science
      Citation Index Expanded until August 2016. We included all randomised clinical
      trials comparing drainage versus no drainage after laparoscopic cholecystectomy
      irrespective of language and publication status. We used standard methodological
      procedures in accordance with the PRISMA guidelines. A total of 2398 participants
      were randomised to drain (1197 participants) versus 'no drain' (1201
      participants) in 16 trials included in this article. Pain 24 h after surgery was
      less severe in the no drain group (MD1.31; 95% CI, 0.96 to 1.65; p < 0.00001).
      Abdominal drainage prolonged operative time (MD 5.77 min; 95% CI 4.98 min-6.57
      min; p < 0.00001) but not the length of hospital stay (MD 0.21 days; 95% CI -0.00
      days to 0.42 days; p = 0.05). No significant difference was present with respect
      to the intra-abdominal fluid, wound infection, nausea or vomit, mortality after
      operation. There is no significant advantage of drain placement after
      laparoscopic cholecystectomy. Further well designed randomized clinical trials
      should be carefully re-considered.

PMID- 27871801
TI  - Lipid profiling of polarized human monocyte-derived macrophages.
AB  - The highly orchestrated transcriptional and metabolic reprogramming during
      activation drastically transforms the main functions and physiology of human
      macrophages across the polarization spectrum. Lipids, for example, can modify
      protein function by acting remotely as signaling molecules but also locally by
      altering the physical properties of cellular membranes. These changes play key
      roles in the functions of highly plastic immune cells due to their involvement in
      inflammation, immune responses, phagocytosis and wound healing processes. We
      report an analysis of major membrane lipids of distinct phenotypes of resting
      (M0), classically activated (M1), alternatively activated (M2a) and deactivated
      (M2c) human monocyte derived macrophages from different donors. Samples were
      subjected to supercritical fluid chromatography-ion mobility-mass spectrometry
      analysis, which allowed separations based on lipid class, facilitating the
      profiling of their fatty acid composition. Different levels of arachidonic acid
      mobilization as well as other fatty acid changes were observed for different
      lipid classes in the distinct polarization phenotypes, suggesting the activation
      of highly orchestrated and specific enzymatic processes in the biosynthesis of
      lipid signaling molecules and cell membrane remodeling. Thromboxane A2 production
      appeared to be a specific marker of M1 polarization. These alterations to the
      global composition of lipid bi-layer membranes in the cell provide a potential
      methodology for the definition and determination of cellular and tissue
      activation states.

PMID- 27871802
TI  - Probiotic normalization of Candida albicans in schizophrenia: A randomized,
      placebo-controlled, longitudinal pilot study.
AB  - The molecules and pathways of the gut-brain axis represent new targets for
      developing methods to diagnose and treat psychiatric disorders. Manipulation of
      the gut microbiome with probiotics may be a therapeutic strategy with the
      potential to relieve gastrointestinal (GI) comorbidities and improve psychiatric
      symptoms. Candida albicans and Saccharomyces cerevisiae, commensal yeast species,
      can be imbalanced in the unhealthy human microbiome, and these fungal exposures
      were previously found elevated in schizophrenia. In a longitudinal, double-blind,
      placebo-controlled, pilot investigation of 56 outpatients with schizophrenia, we
      examined the impact of probiotic treatment on yeast antibody levels, and the
      relationship between treatment and antibody levels on bowel discomfort and
      psychiatric symptoms. We found that probiotic treatment significantly reduced C.
      albicans antibodies over the 14-week study period in males, but not in females.
      Antibody levels of S. cerevisiae were not altered in either treatment group. The
      highest levels of bowel discomfort over time occurred in C. albicans-seropositive
      males receiving the placebo. We observed trends towards improvement in positive
      psychiatric symptoms in males treated with probiotics who were seronegative for
      C. albicans. Results from this pilot study hint at an association of C. albicans
      seropositivity with worse positive psychiatric symptoms, which was confirmed in a
      larger cohort of 384 males with schizophrenia. In conclusion, the administration
      of probiotics may help normalize C. albicans antibody levels and C. albicans
      associated gut discomfort in many male individuals. Studies with larger sample
      sizes are warranted to address the role of probiotics in correcting C. albicans
      associated psychiatric symptoms.

PMID- 27871805
TI  - The survival rate and larynx preservation in elderly cancer patients who received
      surgical operation: A retrospective cohort study.
AB  - BACKGROUND: To investigate the efficiency of surgical operation for patients over
      70 years with hypopharyngeal cancer. MATERIALS AND METHODS: A retrospective
      analysis of the medical records from 68 patients over 70 years-old with
      hypopharyngeal cancer who underwent different therapeutic regimen between 2000
      and 2009 was conducted. 36 of 68 patients underwent larynx preservation. All
      patients were treated with surgical operation and adjuvant radiotherapy. A Kaplan
      Meier method was employed to calculate the survival rate. RESULTS: Overall 3 year
      and 5 year-survival rates were 48.6% and 29.4% respectively. For patients who
      underwent larynx preservation, 5 year-survival rate was 30.5%, which was
      decreased compared to 3 year-survival rate (46.9%) However, 3 year- and 5 year
      survival rates in patients without larynx preservation were 46.9% and 28.1%
      respectively, suggesting that no statistically significant difference of survival
      rates was found between patients with or without larynx preservation (P > 0.05).
      A majority of patients who receive larynx preservation exhibited normal breathing
      and eating abilities and could present an intelligible speech. 16 of 36 patients
      who preserved larynx and 14 of 32 patients who underwent laryngectomy showed
      postoperative complication. No significant difference was observed in these two
      treatments, indicating larynx preservation is not a factor for inducing
      complication. CONCLUSION: This study provides evidence that the quality of life
      for elderly patients with hypopharyngeal cancer can be improved by optimizing the
      therapeutic regimen based on the physical condition of each patient.

PMID- 27871807
TI  - Renal stones editorial.

PMID- 27871804
TI  - Additional surgical resection after endoscopic mucosal dissection for early
      gastric cancer: A medium-sized hospital's experience.
AB  - PURPOSE: In Japan, the majority of early gastric cancers (EGCs) are now treated
      with endoscopic submucosal dissection (ESD). Patients with non-curative lesions
      treated by ESD are advised to undergo additional surgical resection (ASR) based
      on guidelines from the Japan Gastroenterological Endoscopy Society (JGES) and
      Japanese Gastric Cancer Association (JGCA). However, many studies have
      demonstrated that residual cancer and lymph node metastasis are only rarely found
      in ASR specimens. Here we retrospectively analyzed the conditions that could
      enable the avoidance of unnecessary ASR. METHODS: The ESD data for 114 absolute
      indication lesions and 26 lesions of expanded indication lesions were analyzed.
      The indications and the curability were evaluated according to the JGES/JGCA
      guidelines. RESULTS: The rates of non-curative resection and ASR were
      significantly higher in the expanded indication group compared to the absolute
      indication group (26.9% and 19.2% vs. 7.9% and 0.9%, respectively). ASR was
      performed for six patients. Three of their ARS specimens contained neither
      residual cancer nor lymph node metastasis, and the pathological findings of the
      preceding ESD specimens deviated slightly from the curative criteria defined by
      the guidelines. The conditions of the lesions that did not meet the curative
      criteria were as follows: (1) sm1 invasion of undifferentiated-type lesion <10 mm
      dia., (2) 21-25 mm dia. mucosal undifferentiated-type lesion, or (3) peacemeal
      resection with a horizontal margin positive for the mucosal differentiated-type.
      CONCLUSIONS: These data suggest that a close follow-up without ASR might be
      appropriate for patients in the above-mentioned three categories after non
      curative ESD for EGC.

PMID- 27871806
TI  - Does vertebral augmentation lead to an increasing incidence of adjacent vertebral
      failure? A systematic review and meta-analysis.
AB  - BACKGROUND: The aim of the present study was to evaluate whether vertebral
      augmentation technology increases the occurrence of adjacent vertebral fractures
      in patients with osteoporotic vertebral compression fractures (OVCFs). MATERIALS
      AND METHODS: Databases, including MEDLINE, EMBASE and Cochrane library, were
      retrieved via PRISMA covering 1987 to 2015. The number of patients who suffered
      from adjacent secondary vertebral fractures was calculated. A meta-analysis,
      using indexes of odds ratios (OR) and 95% confidence intervals (95% CI), was
      conducted with STATA software. Subgroup investigations were conducted according
      to the operation methods and the duration of observation. Sensitivity analysis
      and publication bias were also evaluated. RESULTS: Ten randomized controlled
      trials (RCTs) met our inclusion criteria. Our results indicated there was no
      statistically significant difference in the occurrence rate of adjacent vertebral
      fractures between manipulation of vertebral augmentation and non-surgical
      treatment (OR = 0.89, 95% CI = 0.58-1.37). Neither subgroup investigations based
      on selection of operation nor duration of follow-up time showed marked
      differences. A sensitivity analysis did not identify specific trails seriously
      deflected. No obvious publication bias was identified. CONCLUSION: Despite
      various limitations in the present study, our data demonstrated that using
      vertebral augmentation was not related to increasing incidence of subsequent
      adjacent vertebral fractures.

PMID- 27871808
TI  - New mechanism of lipotoxicity in diabetic cardiomyopathy: Deficiency of
      Endogenous H2S Production and ER stress.
AB  - OBJECTIVE: To investigate the roles and mechanisms of endogenous hydrogen sulfide
      (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic
      cardiomyopathy (DCM). METHODS: Blood of DCM patients included in the study were
      collected. The model of DCM rats was established using streptozotocin (STZ)
      injection. Cardiac lipotoxicity in vitro models were established using 500MUM
      palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S
      production in plasma, culture supernatant and heart was measured by sulphur ion
      selective electrode assay. Cell viability was tested by using the cell counting
      kit-8 (CCK-8) kit. Glucose regulated protein (GRP78), CCAAT/enhancer binding
      protein homologous transcription factor (C/EBP) homologous protein (CHOP),
      caspase-3 and caspase-12 expressions were measured using western blot analysis.
      Lipid droplet was evaluated by Oil Red O staining. Apoptosis in hearts of DCM
      rats was analyzed using terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) staining. RESULTS: H2S levels in serum of DCM patients and DCM
      rats were significant lower, H2S contents and cystathionine-gamma-lyase (CSE)
      expression in heart tissues of DCM rats were also markedly lower. H2S levels in
      supernatants of PA-treated AC16 cardiac cells were decreased. Cardiac
      lipotoxicity demonstrated by increase in TUNEL positive cells and lipid deposit
      in vivo and in vitro accompanied by a decrease of H2S levels. Pretreatment AC16
      cells with 100MUmol/L of NaHS (a donor of H2S) could suppress the PA-induced
      myocardial injury similar to the effects of 4-phenylbutyric acid (4-PBA, an
      endoplasmic reticulum (ER) stress inhibitor), leading to an increase in cell
      viability and preventing lipid deposit. Meanwhile, administration diabetic rats
      with NaHS or 4-PBA alleviated cardiac lipotoxicity, as evidenced by decrease in
      TUNEL positive cells, cleaved caspase-3 expression and lipid accumulation.
      CONCLUSION: Deficiency of endogenous H2S was involved in lipotoxicity-induced
      myocardial injury. Exogenous H2S attenuates PA-induced myocardial injury though
      inhibition of ER stress.

PMID- 27871809
TI  - Biomarkers for discrimination between latent tuberculosis infection and active
      tuberculosis disease.
AB  - OBJECTIVE: We aimed to determine whether combinations of multiplex cytokine
      responses could differentiate Mycobacterium tuberculosis (Mtb) infection states.
      METHODS: Mtb-specific antigen-induced and unstimulated cytokines were measured by
      Luminex assay in supernatants of QuantiFERON(r) Gold In-Tube assay (QFT) in 48
      active pulmonary TB patients (TB), 15 latent TB infection subjects (LTBI), and 13
      healthy controls (HCs). RESULTS: Among the 29 cytokines, eight Mtb antigen
      specific biomarkers (GM-CSF, IFN-gamma, IL-1RA, IL-2, IL-3, IL-13, IP-10, and MIP
      1beta) in the Mtb-infected group were significantly different from those of the
      HCs. Five Mtb-specific biomarkers (EGF, GM-CSF, IL-5, IL-10, and VEGF), two
      unstimulated biomarkers (TNF-alpha[Nil] and VEGF[Nil]), and one Mtb-specific
      biomarker ratio (IL-2/IFN-gamma) showed significant differences between active TB
      and LTBI. Three unstimulated biomarkers (IL-8[Nil], IL-13[Nil], and VEGF[Nil])
      and 5 Mtb-specific biomarkers (IFN-gamma, IL-2, IL-3, IP-10, and VEGF) were
      significantly different between active TB and non-active TB groups. Combinations
      of three cytokine biomarkers resulted in the accurate prediction of 92.1-93.7% of
      Mtb-infected cases and 92.3-100% of HCs, respectively. Moreover, combinations of
      five biomarkers accurately predicted 90.9-100% of active TB cases and 80-100% of
      LTBI subjects, respectively. In discriminating between active TB and non-active
      TB regardless of QFT results, combinations of six biomarkers predicted 79.2-95.8%
      of active TB cases and 67.9-89.3% of non-active TB subjects. CONCLUSIONS: Taken
      together, our data suggest that combinations of whole blood Mtb antigen-dependent
      cytokines could serve as biomarkers to determine TB disease states. Especially,
      VEGF is highlighted as a key biomarker for reflecting active TB, irrespective of
      stimulation.

PMID- 27871810
TI  - A Maize Gene Regulatory Network for Phenolic Metabolism.
AB  - The translation of the genotype into phenotype, represented for example by the
      expression of genes encoding enzymes required for the biosynthesis of
      phytochemicals that are important for interaction of plants with the environment,
      is largely carried out by transcription factors (TFs) that recognize specific cis
      regulatory elements in the genes that they control. TFs and their target genes
      are organized in gene regulatory networks (GRNs), and thus uncovering GRN
      architecture presents an important biological challenge necessary to explain gene
      regulation. Linking TFs to the genes they control, central to understanding GRNs,
      can be carried out using gene- or TF-centered approaches. In this study, we
      employed a gene-centered approach utilizing the yeast one-hybrid assay to
      generate a network of protein-DNA interactions that participate in the
      transcriptional control of genes involved in the biosynthesis of maize phenolic
      compounds including general phenylpropanoids, lignins, and flavonoids. We
      identified 1100 protein-DNA interactions involving 54 phenolic gene promoters and
      568 TFs. A set of 11 TFs recognized 10 or more promoters, suggesting a role in
      coordinating pathway gene expression. The integration of the gene-centered
      network with information derived from TF-centered approaches provides a
      foundation for a phenolics GRN characterized by interlaced feed-forward loops
      that link developmental regulators with biosynthetic genes.

PMID- 27871811
TI  - Crystal Structure of the Arabidopsis thaliana L1L/NF-YC3 Histone-fold Dimer
      Reveals Specificities of the LEC1 Family of NF-Y Subunits in Plants.

PMID- 27871813
TI  - Gut microbiota in Drosophila melanogaster interacts with Wolbachia but does not
      contribute to Wolbachia-mediated antiviral protection.
AB  - Animals experience near constant infection with microorganisms. A significant
      proportion of these microbiota reside in the alimentary tract. There is a growing
      appreciation for the roles gut microbiota play in host biology. The gut
      microbiota of insects, for example, have been shown to help the host overcome
      pathogen infection either through direct competition or indirectly by stimulating
      host immunity. These defenses may also be supplemented by coinfecting maternally
      inherited microbes such as Wolbachia. The presence of Wolbachia in a host can
      delay and/or reduce death caused by RNA viruses. Whether the gut microbiota of
      the host interacts with Wolbachia, or vice versa, the precise role of Wolbachia
      in antiviral protection is not known. In this study, we used 16S rDNA sequencing
      to characterise changes in gut microbiota composition in Drosophila melanogaster
      associated with Wolbachia infection and antibiotic treatment. We subsequently
      tested whether changes in gut composition via antibiotic treatment altered
      Wolbachia-mediated antiviral properties. We found that both antibiotics and
      Wolbachia significantly reduced the biodiversity of the gut microbiota without
      changing the total microbial load. We also showed that changing the gut
      microbiota composition with antibiotic treatment enhanced Wolbachia density but
      did not confer greater antiviral protection against Drosophila C virus to the
      host. We concluded there are significant interactions between Wolbachia and gut
      microbiota, but changing gut microbiota composition is not likely to be a means
      through which Wolbachia conveys antiviral protection to its host.

PMID- 27871814
TI  - Dr. Alois Huger - Laying the foundations for an integrated insect pathology.
AB  - Dr. Rer. Nat. Alois M. Huger had a long and distinguished career at the Institut
      fur biologische Schadlingsbekampfung (Institute for Biological Pest Control)
      Darmstadt, Germany, where he became one of the world's leading insect
      pathologists. He applied his experience and understanding of insect tissues and
      specialist skills in microscopy to diagnosis and elucidation of the pathology of
      insect diseases. During his career he discovered the Oryctes nudivirus and
      Bacillus thuringiensis subsp. tenebrionis, and was a member of teams unravelling
      amber disease in scarab beetles and the role of bacteria in parthenogenesis of
      parasitoids. He researched and described the life cycles of microsporidian and
      rickettsial pathogens of insects and was the first to describe the ultrastructure
      of a microsporidian spore. Dr. Huger carried out diagnosis of diseased insects
      over a period of 55years and has left us with many publications and a database
      containing thousands of records for ongoing investigation. Working with multiple
      pathogens in different systems, Dr. Huger obtained an overview second to none in
      the complexities of insect/pathogen relationships and has been at the forefront
      of making these discoveries benefit humanity. He is a worthy recipient of the
      Founders' Lecture Honoree Award, the highest honour of the Society for
      Invertebrate Pathology.

PMID- 27871812
TI  - Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on bone mineral
      density and marrow adipose tissue.
AB  - Bariatric surgery is associated with bone loss but skeletal consequences may
      differ between Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), the
      two most commonly performed bariatric procedures. Furthermore, severe weight loss
      is associated with high marrow adipose tissue (MAT); however, MAT is also
      increased in visceral adiposity. The purpose of our study was to determine the
      effects of RYGB and SG on BMD and MAT. We hypothesized that both bariatric
      procedures would lead to a decrease in BMD and MAT. We studied 21 adults with
      morbid obesity (mean BMI 44.1+/-5.1kg/m2) prior to and 12months after RYGB (n=11)
      and SG (n=10). All subjects underwent DXA and QCT of the lumbar spine and hip to
      assess aBMD and vBMD. Visceral (VAT) and subcutaneous (SAT) adipose tissue was
      quantified at L1-L2. MAT of the lumbar spine and femur was assessed by 1H-MR
      spectroscopy. Calcitropic hormones and bone turnover markers were determined. At
      12months after surgery, mean weight and abdominal fat loss was similar between
      the RYGB and SG groups. Mean serum calcium, 25(OH)-vitamin D, and PTH levels were
      unchanged after surgery and within the normal range in both groups. Bone turnover
      markers P1NP and CTX increased within both groups and P1NP increased to a greater
      extent in the RYGB group (p=0.03). There were significant declines from baseline
      in spine aBMD and vBMD within the RYGB and SG groups, although the changes were
      not significantly different between groups (p=0.3). Total hip and femoral neck
      aBMD by DXA decreased to a greater extent in the RYGB than the SG group (p<0.04)
      although the change in femoral vBMD by QCT was not significantly different
      between groups (p>0.2). MAT content of the lumbar spine and femoral diaphysis did
      not change from baseline in the RYGB group but increased after SG (p=0.03).
      Within the SG group, 12-month change in weight and VAT were positively associated
      with 12-month change in MAT (p<0.04), suggesting that subjects with less weight
      and VAT loss had higher MAT. In conclusion, RYGB and SG are associated with
      declines in lumbar spine BMD, however, the changes are not significantly
      different between the groups. RYGB may be associated with greater decline of aBMD
      at the total hip and femoral neck compared to SG. MAT content increased after SG
      and this was associated with lower weight and VAT loss.

PMID- 27871815
TI  - Identification and genomic characterization of a novel rat bocavirus from brown
      rats in China.
AB  - Despite recent discoveries of novel animal bocaparvoviruses, current
      understandings on the diversity and evolution of bocaparvoviruses are still
      limited. We report the identification and genome characterization of a novel
      bocaparvovirus, rat bocaparvovirus (RBoV), in brown rats (Rattus norvegicus) in
      China. RBoV was detected in 11.5%, 2.4%, 16.2% and 0.3% of alimentary,
      respiratory, spleen and kidney samples respectively, of 636 brown rats by PCR,
      but not in samples of other rodent species, suggesting that brown rats are the
      primary reservoir of RBoV. Six RBoV genomes sequenced from three brown rats
      revealed the presence of three ORFs, characteristic of bocaparvoviruses.
      Phylogenetic analysis showed that RBoV was distantly related to other
      bocaparvoviruses, forming a distinct cluster within the genus, with <=55.5%
      nucleotide identities to the genome of ungulate bocaparvovirus 3, supporting its
      classification as a novel bocaparvovirus species. RBoV possessed a putative
      second exon encoding the C-terminal region of NS1 and conserved RNA splicing
      signals, similar to human bocaparvoviruses and canine bocaparvovirus. In contrast
      to human, feline and canine bocaparvoviruses which demonstrates inter/intra-host
      viral diversity, partial VP1/VP2 sequences of 49 RBoV strains demonstrated little
      inter-host genetic diversity, suggesting a single genetic group. Although the
      pathogenicity of RBoV remains to be determined, its presence in different host
      tissues suggests wide tissue tropism. RBoV represents the first bocaparvovirus in
      rodents with genome sequenced, which extends our knowledge on the host range of
      bocaparvoviruses. Further studies are required to better understand the
      epidemiology, genetic diversity and pathogenicity of bocaparvoviruses in
      different rodent populations.

PMID- 27871816
TI  - Experimental transmission of rabbit haemorrhagic disease virus (RHDV) from rabbit
      to wild mice (Mus spretus and Apodemus sylvaticus) under laboratory conditions.
AB  - Rabbit haemorrhagic disease (RHD) is a highly lethal and contagious viral disease
      that produces haemorrhagic lesions in liver and lungs of domestic and wild
      rabbits (Oryctolagus cuniculus). This study investigates the transmission of RHDV
      from infected rabbits to mice, based on the detection of viral RNA. Sixteen wild
      mice (Mus spretus, n=12 and Apodemus sylvaticus, n=4) were put in contact with
      nine rabbits inoculated with RHDV. No mice died following exposure to RHDV
      infected rabbits or developed macroscopic haemorrhagic lesions. On the fourth day
      of contact, RHDV was detected by RT-PCR in the faeces of three of the four mice
      killed and in the livers of two of them. Three days after contact period with the
      inoculated rabbits (7th day of the experiment), RHDV was detected by RT-PCR in
      100% (n=4) of the faeces and 50% (n=2) of the livers of euthanized animals. Ten
      days after contact period (14th day of the experiment), RHDV was not detected in
      the faeces or liver from any of the mice euthanized. However, 64days after
      contact period, RHDV was detected in the faeces of one mouse (1 of 4). We
      demonstrate cross-species transmission of RHDV-RNA from rabbit to rodent and the
      capability of RHDV-RNA to persist in mice for at least 10days after contact, and
      potentially up to two months, although viral replication within the rodent and/or
      infectivity was not evaluated in the present study.

PMID- 27871817
TI  - Two known and one new species of Proctoeces from Australian teleosts: Variable
      host-specificity for closely related species identified through multi-locus
      molecular data.
AB  - Species of Proctoeces Odhner, 1911 (Trematoda: Fellodistomidae) have been
      reported from a wide range of marine animals globally. Members of the genus tend
      to lack strongly distinguishing morphological features for diagnosis, making
      identification difficult and the true number of species in the genus contentious.
      Combined morphological and molecular analyses were used to characterise three
      species of Proctoeces from Moreton Bay and the southern Great Barrier Reef. Data
      for two ribosomal regions and one mitochondrial region were generated for
      specimens collected from Australia. Three unique 18S-genotypes were identified
      which corresponded to subtle, but reliable, morphological differences. Two
      species of Proctoeces were identified from fishes of Moreton Bay, Proctoeces
      insolitus (Nicoll, 1915) Yamaguti, 1953 and P. major Yamaguti, 1934, and a third,
      P. choerodoni n. sp. from off Heron Island on the southern Great Barrier Reef.
      Phylogenetic analyses of partial 18S and partial 28S rDNA indicated that these
      three species differ from the four species reported outside of Australia for
      which sequence data are available. Phylogenetically, Proctoeces proved to be a
      reliable concept, with all species of Proctoeces that have been characterised
      genetically forming a well-supported clade in all analyses. Dramatically
      different patterns of host-specificity were identified for each of the three
      Australian species; P. insolitus apparently infects a single species of fish, P.
      choerodoni n. sp. infects multiple species of a single genus of fish, and P.
      major infects multiple species of two teleost orders.

PMID- 27871818
TI  - Oxidatively generated base modifications in DNA: Not only carcinogenic risk
      factor but also regulatory mark?
AB  - The generation of DNA modifications in cells is in most cases accidental and
      associated with detrimental consequences such as increased mutation rates and an
      elevated risk of malignant transformation. Accordingly, repair enzymes involved
      in the removal of the modifications have primarily a protective function. Among
      the well-established exceptions of this rule are 5-methylcytosine and uracil,
      which are generated in DNA enzymatically under controlled conditions and fulfill
      important regulatory functions in DNA as epigenetic marks and in antibody
      diversification, respectively. More recently, considerable evidence has been
      obtained that also 8-oxo-7,8-dihydroguanine (8-oxoG), a frequent pro-mutagenic
      DNA modification generated by endogenous or exogenous reactive oxygen species
      (ROS), has distinct roles in the regulation of both transcription and signal
      transduction. Thus, the activation of transcription by the estrogen receptor, NF
      kappaB, MYC and other transcription factors was shown to depend on the presence
      of 8-oxoG in the promoter regions and its recognition by the DNA repair
      glycosylase OGG1. The lysine-specific histone demethylase LSD1, which produces
      H2O2 as a by-product, was indentified as a local generator of 8-oxoG in some of
      these cases. In addition, a complex of OGG1 with the excised free substrate base
      was demonstrated to act as a guanine nucleotide exchange factor (GEF) for small
      GTPases such as Ras, Rac and Rho, thus stimulating signal transduction. The
      various findings and intriguing novel mechanisms suggested will be described and
      compared in this review.

PMID- 27871819
TI  - C7 sagittal vertical axis is the determinant of the C5-C7 angle in cervical
      sagittal alignment.
AB  - BACKGROUND CONTEXT: Previous studies have indicated that the T1 slope correlates
      with cervical lordosis. In contrast, the specific impact of the C7 sagittal
      vertical axis (C7SVA) on cervical lordosis remains unknown. PURPOSE: This study
      aimed to investigate the specific role of C7SVA in cervical lordosis. STUDY
      DESIGN/SETTING: This was a retrospective radiographic study. PATIENT SAMPLE:
      Forty-eight consecutive patients who underwent lateral standing radiography of
      the entire spine were retrospectively reviewed. OUTCOME MEASURES: Radiographic
      parameters included occipito (Oc)-C7, Oc-C2, C2-C7, C2-C4, and C5-C7 angles; T1
      slope; C7SVA; T1 pelvic angle (TPA); pelvic incidence; pelvic tilt; and sacral
      slope. METHODS: The radiographs of 96 consecutive patients who underwent lateral
      standing radiography of the entire spine in June 2015 in our hospital were
      retrospectively reviewed. Patients having cervical deformities, having undergone
      cervical fusion, and under 18 years of age were excluded. A total of 48 Asian
      patients (14 men and 34 women; mean age, 54.6 years) were eligible. Pathologies
      included scoliosis, myelopathy, thoracolumbar deformity, and spondylosis.
      Spearman rank correlation coefficients were used to examine correlations between
      the parameters. The relationship between C5-C7 lordosis and the radiographic
      parameters was calculated using the forward stepwise multivariate regression
      analysis. The authors do not have financial associations relevant to this
      article. RESULTS: C7SVA correlated with the Oc-C7 (r=0.42) and C2-C7 (r=0.50)
      angles. However, the correlation coefficient was smaller than that between the T1
      slope and Oc-C7 (r=0.83) or C2-C7 (r=0.76) angles. When the C2-C7 angle was
      divided into C2-C4 and C5-C7 angles, C7SVA correlated with the C5-C7 (r=0.63)
      angle but not with the C2-C4 angle. The correlation coefficient between the C5-C7
      angle and C7SVA was higher than that between the C5-C7 angle and T1 slope
      (r=0.53) or the C5-C7 angle and TPA (r=0.60). Using radiographic parameters and
      age, multiple regression analysis revealed that only C7SVA affected the C5-C7
      angle. CONCLUSIONS: C7SVA was the only radiographic parameter that affected the
      C5-C7 angle. Both T1 slope and C7SVA are key to the shape of the cervical
      sagittal alignment. The results of this study can be a starting point to improve
      our understanding of cervical sagittal alignment.

PMID- 27871820
TI  - Enhanced bone formation in sheep vertebral bodies after minimally invasive
      treatment with a novel, PLGA fiber-reinforced brushite cement.
AB  - BACKGROUND CONTEXT: Injectable, brushite-forming calcium phosphate cements (CPC)
      show potential for bone replacement, but they exhibit low mechanical strength.
      This study tested a CPC reinforced with poly(l-lactide-co-glycolide) acid (PLGA)
      fibers in a minimally invasive, sheep lumbar vertebroplasty model. PURPOSE: The
      study aimed to test the in vivo biocompatibility and osteogenic potential of a
      PLGA fiber-reinforced, brushite-forming CPC in a sheep large animal model. STUDY
      DESIGN/SETTING: This is a prospective experimental animal study. METHODS: Bone
      defects (diameter: 5 mm) were placed in aged, osteopenic female sheep, and left
      empty (L2) or injected with pure CPC (L3) or PLGA fiber-reinforced CPC (L4; fiber
      diameter: 25 um; length: 1 mm; 10% [wt/wt]). Three and 9 months postoperation
      (n=20 each), the structural and functional CPC effects on bone regeneration were
      documented ex vivo by osteodensitometry, histomorphometry, micro-computed
      tomography (micro-CT), and biomechanical testing. RESULTS: Addition of PLGA
      fibers enhanced CPC osteoconductivity and augmented bone formation. This was
      demonstrated by (1) significantly enhanced structural (bone volume/total volume,
      shown by micro-CT and histomorphometry; 3 or 9 months) and bone formation
      parameters (osteoid volume and osteoid surface; 9 months); (2) numerically
      enhanced bone mineral density (3 and 9 months) and biomechanical compression
      strength (9 months); and (3) numerically decreased bone erosion (eroded surface;
      3 and 9 months). CONCLUSIONS: The PLGA fiber-reinforced CPC is highly
      biocompatible and its PLGA fiber component enhanced bone formation. Also, PLGA
      fibers improve the mechanical properties of brittle CPC, with potential
      applicability in load-bearing areas.

PMID- 27871821
TI  - Redox changes in the brains of reproductive female rats during aging.
AB  - Reproduction is a critical and demanding phase of an animal's life. In mammals,
      females usually invest much more in parental care than males, and lactation is
      the most energetically demanding period of a female's life. Here, we tested
      whether oxidative stress is a consequence of reproduction in the brains of female
      Wistar rats. We evaluated the activities of glutathione peroxidase, glutathione S
      transferase, and superoxide dismutase; H2O2 consumption; protein carbonylation;
      NO2 & NO3 levels; and total glutathione, as well as sex hormone levels in brain
      tissue of animals at 3, 6, 12, and 24months of age. Animals were grouped
      according to reproductive experience: breeders or non-breeders. Most of the
      studied parameters showed a difference between non-breeders and breeders at 12
      and 24months. At 24months of age, breeders showed higher superoxide dismutase
      activity, H2O2 consumption, glutathione peroxidase activity, and carbonyl levels
      than non-breeders. In 12-month-old non-breeders, we observed a higher level of
      H2O2 consumption and higher superoxide dismutase and glutathione peroxidase
      activities than breeders. By evaluating the correlation network, we found that
      there were a larger number of influential nodes and positive links in breeder
      animals than in non-breeders, indicating a greater number of redox changes in
      breeder animals. Here, we also demonstrated that the aging process caused higher
      oxidative damage and higher antioxidant defenses in the brains of breeder female
      rats at 24months, suggesting that the reproduction process is costly, at least
      for the female brain. This study shows that there is a strong potential for a
      link between the cost of reproduction and oxidative stress.

PMID- 27871823
TI  - Prediction of microRNAs involved in immune system diseases through network based
      features.
AB  - MicroRNAs are a class of small non-coding regulatory RNA molecules that modulate
      the expression of several genes at post-transcriptional level and play a vital
      role in disease pathogenesis. Recent research shows that a range of miRNAs are
      involved in the regulation of immunity and its deregulation results in immune
      mediated diseases such as cancer, inflammation and autoimmune diseases.
      Computational discovery of these immune miRNAs using a set of specific features
      is highly desirable. In the current investigation, we present a SVM based
      classification system which uses a set of novel network based topological and
      motif features in addition to the baseline sequential and structural features to
      predict immune specific miRNAs from other non-immune miRNAs. The classifier was
      trained and tested on a balanced set of equal number of positive and negative
      examples to show the discriminative power of our network features. Experimental
      results show that our approach achieves an accuracy of 90.2% and outperforms the
      classification accuracy of 63.2% reported using the traditional miRNA sequential
      and structural features. The proposed classifier was further validated with two
      immune disease sub-class datasets related to multiple sclerosis microarray data
      and psoriasis RNA-seq data with higher accuracy. These results indicate that our
      classifier which uses network and motif features along with sequential and
      structural features will lead to significant improvement in classifying immune
      miRNAs and hence can be applied to identify other specific classes of miRNAs as
      an extensible miRNA classification system.

PMID- 27871822
TI  - Geroscience: Addressing the mismatch between its exciting research opportunities,
      its economic imperative and its current funding crisis.
AB  - There is at present a huge disconnect between levels of funding for basic
      research on fundamental mechanisms of biological aging and, given demographic
      projections, the anticipated enormous social and economic impacts of a litany of
      chronic diseases for which aging is by far the major risk factor: One valuable
      approach, recently instigated by Felipe Sierra & colleagues at the US National
      Institute on Aging, is the development of a Geroscience Interest Group among
      virtually all of the NIH institutes. A complementary approach would be to seek
      major escalations of private funding. The American Federation for Aging Research,
      the Paul Glenn Foundation and the Ellison Medical Foundation pioneered efforts by
      the private sector to provide substantial supplements to public sources of
      funding. It is time for our community to organize efforts towards the
      enhancements of such crucial contributions, especially in support of the emerging
      generation of young investigators, many of whom are leaving our ranks to seek
      alternative employment. To do so, we must provide potential donors with strong
      economic, humanitarian and scientific rationales. An initial approach to such
      efforts is briefly outlined in this manuscript as a basis for wider discussions
      within our community.

PMID- 27871824
TI  - Cocaine self-administration, extinction training and drug-induced relapse change
      metabotropic glutamate mGlu5 receptors expression: Evidence from radioligand
      binding and immunohistochemistry assays.
AB  - Several behavioral findings highlight the importance of glutamatergic
      transmission and its metabotropic receptor type 5 (mGlu5) in the controlling of
      cocaine reward and seeking behaviors. The molecular or neurochemical nature of
      such interactions is not well recognized, so in the present paper we determine if
      cocaine self-administration and extinction/reinstatement models with the yoked
      triad control procedure alter mGlu5 receptor density in rats. [3H]MPEP was used
      to evaluate mGlu5 receptors density and affinity in selected brain structures,
      while immunofluorescence analysis was used to detect changes in mGlu5 receptors'
      brain location. Cocaine self-administration and yoked cocaine delivery evoked a
      significant elevation in mGlu5 receptors' density in the dorsal striatum, while
      receptor protein expression was importantly elevated in the substantia nigra and
      reduced in the nucleus accumbens shell. Cocaine administration followed by 10
      extinction training sessions resulted in biphasic mGlu5 receptor density changes
      in the prefrontal cortex-nucleus accumbens pathway. mGlu5 receptors' up
      regulation was noted for cocaine self-administration and extinction training in
      the hippocampus and in yoked cocaine controls following drug abstinence in the
      dorsal striatum. A cocaine priming dose (but not a saline priming) resulted in a
      significant decrease of mGlu5 receptors' density in the nucleus accumbens of rats
      previously treated with the drug and in the hippocampus of rats previously self
      administered cocaine. The latter decrease in mGlu5 receptors' density and protein
      expression in the hippocampus was parallel to an increase in [3H]MPEP affinity
      and opposite to a rise observed after single cocaine administration (ip) to drug
      naive yoked saline controls. Additionally, we also observed a significant
      elevation in the protein expression of the tested receptors in the limbic cortex
      in both cocaine groups. The present results shown modality dependent and brain
      region specific changes in mGlu5 receptors' localization and membrane specific
      binding.

PMID- 27871825
TI  - Re: Kim et al.: Are Urologists Performing Semi-rigid Ureteroscopic Lithotripsy
      Safe From Radiation Exposure? A Guidance to Reduce the Radiation Dose (Urology
      2016;95:54-59).

PMID- 27871826
TI  - Eroded Tape: A Case of an Early Vesicoscopy Rather Than Laser Melting.
AB  - OBJECTIVE: To report our experience on vesicoscopic excision of eroded foreign
      material in the bladder. MATERIALS AND METHODS: The use of xenografts in female
      urology is becoming more prevalent and so are their complications. Erosion of
      foreign material into the bladder often goes unrecognized for a long time and
      patients are troubled by irritative urinary symptoms, recurrent infections, and
      stone formation. The treatment of such erosions is traditionally reported through
      the transurethral route using laser or electrocautery to cut the foreign
      material. Such methods have a high rate of incomplete material removal and as a
      result a high recurrence rate. Leaving a urothelial defect results in prolonged
      time to symptom resolution. Between 2012 and 2015, 5 patients with eroded tapes
      were referred for tertiary care to King's College Hospital and Ygia Polyclinic;
      all patients had undergone a variety of endoscopic, vaginal, and/or open attempts
      for mesh removal that failed. We offered vesicoscopic excision of the eroded
      portion of the tape. RESULTS: We here report 5 cases with tape erosions referred
      to our team that were treated with vesicoscopic excision of the material and
      primary closure of the urothelial defect. The foreign material was completely
      removed in all cases and there is no recurrence at a median follow-up of 30
      months. CONCLUSION: Vesicoscopic excision of bladder-eroded foreign material is
      feasible and efficient. We recommend this technique to be considered as a primary
      approach to tapes eroding into the bladder.

PMID- 27871827
TI  - Asymptomatic Infection With Mycoplasma hominis Negatively Affects Semen
      Parameters and Leads to Male Infertility as Confirmed by Improved Semen
      Parameters After Antibiotic Treatment.
AB  - OBJECTIVE: To elucidate the association between asymptomatic infections caused by
      Mycoplasma hominis and male infertility and to evaluate the role of antibiotic
      therapy in the treatment of this failure. MATERIALS AND METHODS: A total of 165
      infertile men having abnormal semen parameters (study group) as well as 165
      healthy fertile men (control group) were included in this study. Semen samples
      were taken from all participants and, after analyzing for semen parameters, real
      time polymerase chain reaction, microbial culture, and reactive oxygen species
      (ROS) as well as total antioxidant capacity (TAC) assays were performed. Infected
      individuals of the study group were treated with antibiotic. One month after the
      treatment completion, second semen samples were taken and all the tests mentioned
      were performed. The data were analyzed using SPSS statistical software, version
      22.0. RESULTS: The frequency of M. hominis was significantly higher in the
      infertile men compared with the fertile ones (14.5% vs 3.6%, P = .001). The mean
      cycle threshold (Ct) value was lower in infected infertile men than in infected
      fertile men (P < .001). All semen parameters, except volume, pH, and viscosity,
      were improved (P < .05), most of which reached their normal range; leukocytes in
      seminal fluid were eliminated (P = .04); the level of TAC elevated (P < .001);
      and the ROS level as well as the ROS-to-TAC ratio reduced after antibiotic
      treatment (P = .02). Moreover, wives of 14 infected infertile men (58.3%) became
      pregnant 4 months after the treatment completion. CONCLUSION: Our data suggest
      that asymptomatic infection caused by M. hominis is correlated with male
      infertility and antibiotic therapy can improve the semen quality and fairly treat
      the male infertility.

PMID- 27871828
TI  - Pain Associated With Urethral Catheterization Is Reduced in Males by Simultaneous
      Voiding Maneuver.
AB  - OBJECTIVE: To assess whether urethral pain during male catheterization can be
      reduced if the patient is instructed to void during the insertion of the
      catheter. METHODS: Ninety-six males (age 66 +/- 13) who were referred for
      multichannel urodynamic study were prospectively randomized to 2 groups according
      to the catheter insertion technique: (1) patients who were instructed to void
      during catheterization, and (2) patients who had no guidance prior or during
      catheterization. Exclusion criteria were the following: use of analgesics within
      the previous 24 hours, active urinary tract infection, indwelling urethral
      catheter, pre-existing urethral pain, and known urethral stricture or inability
      to cooperate with pain assessment due to mental disorders. A 0 to 10 visual
      analog pain scale was filled in different time points: prior and immediately
      after instillation of the lubricant gel into the urethra, immediately after the
      insertion of the catheter, and 15 minutes after the test. RESULTS: Study groups
      did not differ in terms of demographic, clinical, and urodynamic parameters. The
      median visual analog pain scale during catheterization was 2 (interquartile range
      1-3) and 4 (interquartile range 3-5) in groups 1 and 2, respectively (P < .001).
      There were no differences in the reported scores in the other checkpoints.
      CONCLUSION: Pain level during urethral cauterization in males can be
      significantly reduced when the patient is instructed to void during the insertion
      of the catheter into the urethra.

PMID- 27871829
TI  - The Role of Ipsilateral and Contralateral Transrectal Ultrasound-guided
      Systematic Prostate Biopsy in Men With Unilateral Magnetic Resonance Imaging
      Lesion Undergoing Magnetic Resonance Imaging-ultrasound Fusion-targeted Prostate
      Biopsy.
AB  - OBJECTIVE: To determine how ipsilateral (ipsi) and contralateral (contra)
      systematic biopsies (SB) impact detection of clinically significant vs
      insignificant prostate cancer (PCa) in men with unilateral magnetic resonance
      imaging (MRI) lesion undergoing MRI-ultrasound fusion-targeted biopsy (MRF-TB).
      MATERIALS AND METHODS: A total of 211 cases with 1 unilateral MRI lesion were
      subjected to SB and MRF-TB. Biopsy tissue cores from the MRF-TB, ipsi-SB, and
      contra-SB were analyzed separately. RESULTS: A direct relationship was observed
      between MRI suspicion score and (1) detection of any cancer, (2) Gleason 6 PCa,
      and (3) Gleason >6 PCa. MRF-TB alone, MRF-TB + ipsi-SB, and MRF-TB + contra-SB
      detected 64.1%, 89.1%, and 76.1% of all PCa, respectively; 53.5%, 81.4%, and
      69.8% of Gleason 6 PCa, respectively; and 73.5%, 96.0%, and 81.6% of Gleason >6
      PCa, respectively. MRF-TB + ipsi-SB detected 96% of clinically significant PCa
      and avoided detection of 18.6% of clinically insignificant PCa. MRF-TB + contra
      SB detected 81.6% of clinically significant PCa and avoided detection of 30.2% of
      clinically insignificant PCa. CONCLUSION: Our study suggests that ipsi-SB should
      be added to MRF-TB, as detection of clinically significant PCa increases with
      only a modest increase in clinically insignificant PCa detection. Contra-SB in
      this setting may be deferred because it primarily detects clinically
      insignificant PCa.

PMID- 27871830
TI  - Characterization and antiviral activity of a newly identified defensin-like
      peptide, HEdefensin, in the hard tick Haemaphysalis longicornis.
AB  - Tick defensins are antimicrobial peptides that play a major role in the innate
      immunity of ticks by providing a direct antimicrobial defense. In this study, we
      identified and characterized a defensin-like encoding gene, HEdefensin, from the
      expressed sequence tags (EST) database of hemolymph from the hard tick
      Haemaphysalis longicornis. Expression of the gene in whole adult ticks and in
      different organs was upregulated during blood feeding, though not after Langat
      virus (LGTV) challenge. A synthetic HEdefensin peptide demonstrated significant
      virucidal activity against LGTV but not against an adenovirus in co-incubation
      virucidal assays. Moreover, the RNAi-mediated gene silencing of HEdefensin did
      not significantly affect the virus titer as compared to the control group. The
      data reported here have established the in vitro virucidal activity of the
      peptide against LGTV. However, its role in the innate antiviral immunity of H.
      longicornis remains to be explored, and further studies are needed to fully
      evaluate the potential biological activities of the peptide against bacteria,
      fungi or parasites.

PMID- 27871831
TI  - Bovine milk RNases modulate pro-inflammatory responses induced by nucleic acids
      in cultured immune and epithelial cells.
AB  - Activation of innate immune receptors by exogenous substances is crucial for the
      detection of microbial pathogens and a subsequent inflammatory response. The
      inflammatory response to microbial lipopolysaccharide via Toll-like receptor 4
      (TLR4) is facilitated by soluble accessory proteins, but the role of such
      proteins in the activation of other pathogen recognition receptors for microbial
      nucleic acid is not well understood. Here we demonstrate that RNase4 and RNase5
      purified from bovine milk bind to Salmonella typhimurium DNA and stimulate pro
      inflammatory responses induced by nucleic acid mimetics and S. typhimurium DNA in
      an established mouse macrophage cell culture model, RAW264.7, as well as in
      primary bovine mammary epithelial cells. RNase4 and 5 also modulated pro
      inflammatory signalling in response to nucleic acids in bovine peripheral blood
      mononuclear cells, although producing a distinct response. These results support
      a role for RNase4 and RNase5 in mediating inflammatory signals in both immune and
      epithelial cells, involving mechanisms that are cell-type specific.

PMID- 27871832
TI  - Genome-wide miRNA screening reveals miR-310 family members negatively regulate
      the immune response in Drosophila melanogaster via co-targeting Drosomycin.
AB  - Although innate immunity mediated by Toll signaling has been extensively studied
      in Drosophila melanogaster, the role of miRNAs in regulating the Toll-mediated
      immune response remains largely unknown. In this study, following Gram-positive
      bacterial challenge, we identified 93 differentially expressed miRNAs via genome
      wide miRNA screening. These miRNAs were regarded as immune response related
      (IRR). Eight miRNAs were confirmed to be involved in the Toll-mediated immune
      response upon Gram-positive bacterial infection through genetic screening of 41
      UAS-miRNA lines covering 60 miRNAs of the 93 IRR miRNAs. Interestingly, four out
      of these eight miRNAs, miR-310, miR-311, miR-312 and miR-313, are clustered
      miRNAs and belong to the miR-310 family. These miR-310 family members were shown
      to target and regulate the expression of Drosomycin, an antimicrobial peptide
      produced by Toll signaling. Taken together, our study implies important
      regulatory roles of miRNAs in the Toll-mediated innate immune response of
      Drosophila upon Gram-positive bacterial infection.

PMID- 27871833
TI  - Oral hesperidin-Amorphization and improved dissolution properties by controlled
      loading onto porous silica.
AB  - The oral bioavailability of poorly soluble drugs can be improved by amorphization
      generated by loading into the pores of mesoporous particles (pore size 2-50nm).
      The main mechanisms are increased kinetic saturation solubility and dissolution
      velocity due to the amorphous drug state and the nano-size of the drug
      (=increased dissolution pressure). In this study, the maximum achievable drug
      loading compared to the theoretical drug loading, and the effect of drug loading
      degree on the dissolution properties (solubility, dissolution velocity) were
      investigated. Hesperidin was used as the model active (having also practical
      relevance for e.g. nutraceutical products), loading was performed onto
      AEROPERL(r) 300 Pharma. Degree of successful drug loading could be easily
      followed by simple light microscopy (=useful tool for formulation optimization),
      and was in agreement with scanning electron microscopy. Amorphous versus
      crystalline state was followed by X-ray diffraction and differential scanning
      calorimetry. Loadings prepared were 28.6wt.%, 54.5wt.% and 60.0wt.%, the maximum
      theoretical loading was 72.5wt.%. Obviously the maximum drug loading is not
      achievable, the 54.5wt.% drug loading was the practical maximum with already some
      minor crystalline hesperidin on the surface. Interestingly, the maximum kinetic
      saturation solubility was obtained for the 54.5wt.% drug loading (941.74MUg/ml in
      pH 6.8 PBS), versus 408.80MUg/ml for the 60.0wt.% drug loading (=overloaded
      system). The raw drug powder had a thermodynamic solubility of only 18.40MUg/ml.
      The fastest in vitro release was obtained with the 28.6wt.% loaded system,
      followed by the 54.5wt.% and 60.0wt.% loadings. The dissolution properties
      (solubility, dissolution velocity) can obviously be influenced by a "controlled
      loading". This is a simple, cost-effective technological alternative to
      modulating this property by chemical modification of silica, requiring a new
      costly regulatory approval of these chemically modified materials.

PMID- 27871834
TI  - pH-Sensitive PEGylated liposomes for delivery of an acidic dinitrobenzamide
      mustard prodrug: Pathways of internalization, cellular trafficking and
      cytotoxicity to cancer cells.
AB  - This paper aims to develop and evaluate a pH-sensitive PEGylated liposomal (pPSL)
      system for tumor-targeted intracellular delivery of SN25860, a weakly acidic,
      poorly water-soluble dinitrobenzamide mustard prodrug which is activated by the
      E. coli nitroreductase nfB. pPSL and non pH-sensitive liposomes (nPSL), as
      reference, were formulated by thin-film hydration; an active drug loading method
      was developed with the aid of solubilizers. Cytotoxicity was evaluated in an nfsB
      transfected EMT6 mouse mammary carcinoma cell line. Cellular uptake of liposomes
      was evaluated by both high performance liquid chromatography and flow cytometry.
      Intracellular trafficking was visualised by confocal microscopy. High drug
      loading (7.0+/-0.2% w/w) was achieved after systematic optimization of drug
      loading conditions. pPSL-SN25860 demonstrated a 21 and 24- fold increase in
      antiproliferative potency compared to nPSL-SN25860 and free drug, respectively.
      Cells treated with pPSL had a 1.6-2.5- fold increase in intracellular drug
      concentration compared to nPSL. This trend was consistent with flow cytometry
      results. Cells treated with chlorpromazine demonstrated reduced uptake of both
      nPSL (40%) and pPSL (46%), indicating clathrin-mediated endocytosis was the major
      pathway. Confocal microscopy showed that pPSL had not only undergone faster and
      greater endocytosis than nPSL but was also homogeneously distributed in the
      cytosol and nuclei suggesting endosome escape, in contrast to nPSL.

PMID- 27871835
TI  - Development of flexible nanocarriers for siRNA delivery into tumor tissue.
AB  - Various non-viral delivery systems for small interfering RNAs (siRNA) have been
      developed. Such delivery systems generally exhibit tightly formed spherical
      structures. While such carriers have demonstrated good transfection activity in
      mono-layered cell systems, effects against solid tumors are often less apparent
      and difficult to demonstrate, likely due to the rigid structures of the carriers,
      which may prevent penetration to deeper regions within tumor tissue. Herein, we
      developed a flexible nanocarrier (FNC) system that is able to penetrate to deeper
      regions within tumor tissue. Specifically, we employed previously found flexible
      polyplexes comprised of siRNA and poly-l-lysine as wick structures for the
      preparation of FNCs. FNCs were constructed by coating the wick structures with
      lipids using a liposomal membrane fusion method. The diameters of the resulting
      FNCs were ca. 170nm, and the shapes were non-spherical. Lipid coating was
      confirmed using a nuclease resistance assay. Furthermore, FNCs showed significant
      RNA interference effects, comparable to Lipofectamine 2000, in a mono-layered
      cell system. To accelerate tumor penetration, the FNC surface was modified with
      polyethylene glycol (PEG) and the tight junction opener peptide AT1002. Surface
      modified FNCs demonstrated effective penetrability into a cancer spheroid. Thus,
      we developed a novel and unique tumor-penetrable siRNA FNC system.

PMID- 27871836
TI  - Sentinel lymph node assessment in endometrial cancer: a systematic review and
      meta-analysis.
AB  - BACKGROUND: In the staging of endometrial cancer, controversy remains regarding
      the role of sentinel lymph node mapping compared with other nodal assessment
      strategies. OBJECTIVE: We conducted a systematic review to evaluate the
      diagnostic accuracy and clinical impact of sentinel lymph node mapping in the
      management of endometrial cancer. DATA SOURCES: We searched Medline, Embase, and
      the Cochrane Central Registry of Controlled trials for studies published in
      English before March 25, 2016 (PROSPERO CRD42016036503). STUDY ELIGIBILITY
      CRITERIA: Studies were included if they contained 10 or more women with
      endometrial cancer and reported on the detection rate, sensitivity, and/or impact
      on treatment or survival of sentinel lymph node mapping. STUDY APPRAISAL AND
      SYNTHESIS METHODS: Two authors independently reviewed abstracts and full-text
      articles for inclusion and assessed study quality. The detection rate,
      sensitivity, and factors associated with successful mapping (study size, body
      mass index, tumor histology and grade, injection site, dye type) were synthesized
      through random-effects meta-analyses and meta-regression. RESULTS: We identified
      55 eligible studies, which included 4915 women. The overall detection rate of
      sentinel lymph node mapping was 81% (95% confidence interval, 77-84) with a 50%
      (95% confidence interval, 44-56) bilateral pelvic node detection rate and 17%
      (95% confidence interval, 11-23) paraaortic detection rate. There was no
      difference in detection rates by patient body mass index or tumor histology and
      grade. Use of indocyanine green increased the bilateral detection rate compared
      with blue dye. Additionally, cervical injection increased the bilateral sentinel
      lymph node detection rate but decreased the paraaortic detection rate compared
      with alternative injection techniques. Intraoperative sentinel lymph node frozen
      section increased the overall and bilateral detection rates. The sensitivity of
      sentinel node mapping to detect metastases was 96% (95% confidence interval, 91
      98); ultrastaging did not improve sensitivity. Compared with women staged with
      complete lymphadenectomy, women staged with sentinel lymph node mapping were more
      likely to receive adjuvant treatment. CONCLUSION: Sentinel lymph node mapping is
      feasible and accurately predicts nodal status in women with endometrial cancer.
      The current data favors the use of cervical injection techniques with indocyanine
      green. Sentinel lymph mapping may be considered an alternative standard of care
      in the staging of women with endometrial cancer.

PMID- 27871837
TI  - Modifying the risk of recurrent preterm birth: influence of trimester-specific
      changes in smoking behaviors.
AB  - BACKGROUND: Women with at least 1 prior occurrence of premature birth often have
      demographic and medical risk factors that are not modifiable. However, smoking
      cessation could be a targeted intervention in which a woman with a history of
      premature birth may be able to reduce her future risk of recurrence. OBJECTIVE:
      This study aims to assess how trimester-specific smoking patterns influence the
      risk of recurrent premature birth. STUDY DESIGN: This was a population-based
      retrospective cohort study of singleton nonanomalous live births in Ohio, 2006
      2012 using vital statistics birth records. This analysis was limited to women
      with at least 1 prior premature birth. Rates of birth <37 weeks were compared
      among nonsmokers, women who smoked in the 3 months prior to pregnancy and quit in
      the first vs quit in the second vs quit in the third trimester. Multivariate
      logistic regression analyses assessed the association between smoking cessation
      at various time points in pregnancy and recurrent premature birth while adjusting
      for maternal race, education, Medicaid enrollment, and marital status. RESULTS:
      We analyzed the outcomes of 36,432 women with a prior premature birth who
      subsequently delivered at 20-42 weeks. One third of women with a prior premature
      birth smoked during pregnancy. Of smokers, 16% quit early in the first trimester,
      7% quit in the second, 5% quit in the third trimester, and 72% smoked throughout
      pregnancy. The rate of recurrent premature birth in nonsmokers was high 28% in
      this cohort. Smoking in pregnancy with cessation in the first or second trimester
      was not significantly associated with an increase in recurrent premature birth
      rates (first trimester, 29% adjusted odds ratio, 0.97 [95% confidence interval,
      0.9-1.1], and second trimester, 31% adjusted odds ratio, 1.10 [95% confidence
      interval, 0.9-1.3], respectively). However, quitting late in pregnancy (third
      trimester) was associated with a high rate (43%) of delivery <37 weeks, adjusted
      odds ratio, 1.81 (95% confidence interval, 1.48-2.21). Continued smoking
      throughout pregnancy was also associated with an increased recurrent premature
      birth (32%), adjusted odds ratio, 1.14 (95% confidence interval, 1.07-1.22),
      despite adjustment for concomitant premature birth risk factors. CONCLUSION:
      Smoking cessation in pregnancy and its relationship to preterm birth has been
      studied extensively, and it is widely accepted that smoking in pregnancy
      increases preterm birth rates. However, this study provides novel information
      quantifying the risk of recurrent preterm birth and stratifies the increased risk
      of recurrent preterm birth by trimester-specific smoking behavior. Although women
      with even 1 prior premature birth are at an inherently high risk of recurrence,
      women who stopped smoking early in the first 2 trimesters experienced similar
      preterm birth rates compared with nonsmokers. However, delayed smoking cessation
      or smoking throughout pregnancy significantly increased recurrent premature birth
      risk. Smoking cessation is a potential modifiable risk factor for recurrent
      preterm birth in high-risk pregnancies. This study highlights the importance of
      early pregnancy smoking cessation in those at especially high risk, women with a
      prior preterm birth.

PMID- 27871839
TI  - Interactions of two structurally related anionic phospholipids cardiolipin and
      phosphatidylglycerol with phospholipase A2. Langmuir monolayer studies.
AB  - Anionic phospholipids cardiolipins (CL) and phosphatidylglycerols (PG) dominate
      in the biomembranes of the majority of soil bacteria. CL to PG ratio differs
      between the species and is also dependent on the external conditions. CL/PG ratio
      is different in polluted than in unspoiled soils and it was hypothesized that it
      is connected with the activity of the membranelytic enzymes from the
      phospholipase A2 class (PLA2) as it was proved that persistent soil pollutants
      can activate PLA2. In our studies we applied the Langmuir monolayer technique and
      Brewster angle microscopy to elucidate the mechanism of the interactions of PLA2
      with the model membranes formed by anionic phospholipids. It turned out that
      there are significant differences between CL and PG. The monolayer of PG is
      hydrolyzed readily and entirely, whereas for CL approximately 30% of the
      phospholipid molecules are hydrolyzed after which the enzyme is inhibited. The
      observed differences between PG and CL are strictly connected with the
      hydrophobicity of the generated lysolipids: lyso-PG and lyso-CL. Lyso-PG is water
      soluble and leaves the interface whereas lyso-CL is water-insoluble remains at
      the interface and modifies the monolayer properties. The second hydrolysis
      product - myristic acid (MA) forms crystallites of calcium myristate when
      generated from PG, whereas when generated from CL it is shielded by the lysolipid
      and does not interact with calcium. Therefore, on the basis of our study it can
      be concluded that the increase in CL content protects the soil bacteria from PLA2
      activity and from the loss of calcium homeostasis.

PMID- 27871838
TI  - Chronic insulin infusion induces reversible glucose intolerance in lean rats yet
      ameliorates glucose intolerance in obese rats.
AB  - BACKGROUND: Although insulin resistance (IR) is a key factor in the pathogenesis
      of type 2 diabetes (T2D), the precise role of insulin in the development of IR
      remains unclear. Therefore, we investigated whether chronic basal insulin
      infusion is causative in the development of glucose intolerance. METHODS:
      Normoglycemic lean rats surgically instrumented with i.v. catheters were infused
      with insulin (3mU/kg/min) or physiological saline for 6weeks. At infusion-end,
      plasma insulin levels along with glucose tolerance were assessed. RESULTS: Six
      weeks of insulin infusion induced glucose intolerance and impaired insulin
      response in healthy rats. Interestingly, the effects of chronic insulin infusion
      were completely normalized following 24h withdrawal of exogenous insulin and
      plasma insulin response to glucose challenge was enhanced, suggesting improved
      insulin secretory capacity. As a result of this finding, we assessed whether the
      effects of insulin therapy followed by a washout could ameliorate established
      glucose intolerance in obese rats. Obese rats were similarly instrumented and
      infused with insulin or physiological saline for 7days followed by 24h washout.
      Seven day-insulin therapy in obese rats significantly improved glucose tolerance,
      which was attributed to improved insulin secretory capacity and improved insulin
      signaling in liver and skeletal muscle. CONCLUSION: Moderate infusion of insulin
      alone is sufficient to cause glucose intolerance and impair endogenous insulin
      secretory capacity, whereas short-term, intensive insulin therapy followed by
      insulin removal effectively improves glucose tolerance, insulin response and
      peripheral insulin sensitivity in obese rats. GENERAL SIGNIFICANCE: New insight
      into the link between insulin and glucose intolerance may optimize T2D
      management.

PMID- 27871840
TI  - Probing the structure of the uncoupled nicotinic acetylcholine receptor.
AB  - In the absence of activating anionic lipids and cholesterol, the nicotinic
      acetylcholine receptor (nAChR) from Torpedo adopts an uncoupled conformation that
      does not usually gate open in response to agonist. The uncoupled conformation
      binds both agonists and non-competitive channel blockers with a lower affinity
      than the desensitized state, consistent with both the extracellular agonist
      binding and transmembrane channel-gating domains individually adopting resting
      state like conformations. To test this hypothesis, we characterized the binding
      of the agonist, acetylcholine, and two fluorescent channel blockers, ethidium and
      crystal violet, to resting, desensitized and uncoupled nAChRs in reconstituted
      membranes. The measured Kd for acetylcholine binding to the uncoupled nAChR is
      similar to that for the resting state, confirming that the agonist binding site
      adopts a resting-state like conformation. Although both ethidium and crystal
      violet bind to the resting and desensitized channel pores with distinct
      affinities, no binding of either probe was detected to the uncoupled nAChR. Our
      data suggest that the transmembrane domain of the uncoupled nAChR adopts a
      conformation distinct from that of the resting and desensitized states. The lack
      of binding is consistent with a more constricted channel pore, possibly along the
      lines of what is observed in crystal structures of the prokaryotic homolog, ELIC.

PMID- 27871841
TI  - Rubber particle proteins REF1 and SRPP1 interact differently with native lipids
      extracted from Hevea brasiliensis latex.
AB  - Rubber particle membranes from the Hevea latex contain predominantly two
      proteins, REF1 and SRPP1 involved in poly(cis-1,4-isoprene) synthesis or rubber
      quality. The repartition of both proteins on the small or large rubber particles
      seems to differ, but their role in the irreversible coagulation of the rubber
      particle is still unknown. In this study we highlighted the different modes of
      interactions of both recombinant proteins with different classes of lipids
      extracted from Hevea brasiliensis latex, and defined as phospholipids (PL),
      glycolipids (GL) and neutral lipids (NL). We combined two biophysical methods,
      polarization modulated-infrared reflection adsorption spectroscopy (PM-IRRAS) and
      ellipsometry to elucidate their interactions with monolayers of each class of
      lipids. REF1 and SRPP1 interactions with native lipids are clearly different;
      SRPP1 interacts mostly in surface with PL, GL or NL, without modification of its
      structure. In contrast REF1 inserts deeply in the lipid monolayers with all lipid
      classes. With NL, REF1 is even able to switch from alpha-helice conformation to
      beta-sheet structure, as in its aggregated form (amyloid form). Interaction
      between REF1 and NL may therefore have a specific role in the irreversible
      coagulation of rubber particles.

PMID- 27871842
TI  - Evaluation of risk for metabolic syndrome according to the fasting insulin
      concentration in Korean men.
AB  - BACKGROUND: As a well-known risk factor for cardiovascular disease, metabolic
      syndrome (MetS) is an important global health problem due to its high worldwide
      prevalence. The objective of this study is to determine whether the fasting serum
      insulin concentration influences future incidence of MetS. METHODS: A total of
      14,621 Korean men without MetS participating in a medical health check-up program
      were followed up from 2005 until 2010. They were divided into 4 groups according
      to baseline fasting insulin concentrations. The incidence of MetS was compared
      among the groups, and Cox proportional hazards model was used to determine if
      MetS was associated with higher fasting insulin concentration. RESULTS: The
      incidence of MetS increased according to the baseline fasting insulin
      concentration (first quartile: 8.4%, second quartile: 12.3%, third quartile:
      16.3%, fourth quartile: 26.5%, P<0.001). Even after adjusting for multiple
      covariates, the hazard ratio (95% CI) for MetS was higher for the second (1.13
      (0.93-1.37)), third (1.29 (1.06-1.56)) and fourth quartile group (1.70 (1.36
      2.13)), compared to the first quartile group (P for trend <0.001). CONCLUSION:
      The incidence of MetS increased proportionally to fasting insulin concentration.
      Additionally, increased fasting insulin concentration was an independent risk
      factor for the future development of MetS.

PMID- 27871843
TI  - Considerations when using next-generation sequencing for genetic diagnosis of
      long-QT syndrome in the clinical testing laboratory.
AB  - BACKGROUND: Congenital long-QT syndrome (LQTS) is a potentially lethal cardiac
      electrophysiologic disorder characterized by QT interval prolongation and T-wave
      abnormalities. At least 13 LQTS-associated genes have been reported, but the high
      cost and low throughput of conventional Sanger sequencing has hampered the multi
      gene-based LQTS diagnosis in clinical laboratories. METHODS: We developed an NGS
      (next-generation sequencing)-based targeted gene panel for 13 LQTS genes using
      the Ion PGM platform, and a cohort of 36 LQTS patients were studied for
      characterization of analytical performance specifications. RESULTS: This panel
      efficiently explored 212 of all 221 coding exons in 13 LQTS-associated genes. And
      for those genomic regions covered by the design of the NGS panel, the analytical
      sensitivity and analytical specificity for all potentially pathogenic variants
      were both 100% and showed 100% concordance with clinically validated Sanger
      sequencing results in five major LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, and
      KCNE2). CONCLUSION: This is the first description of an NGS panel targeting a
      multi-gene panel of 13 LQTS-associated genes. We developed and validated this
      robust, high-throughput NGS test and informatics pipeline for LQTS diagnosis
      suitable for the clinical testing laboratory.

PMID- 27871844
TI  - An LC-MS/MS based candidate reference method for the quantification of total
      gentamicin in human serum and plasma using NMR characterized calibrator material.
AB  - BACKGROUND: Accurate measurement of gentamicin concentration in serum and plasma
      is required for therapeutic drug monitoring to ensure appropriate treatment of
      patients. In this work, we present a validated LC-MS/MS-based candidate reference
      measurement procedure for total gentamicin quantification to be used for
      standardization and harmonization of routine assays applied for therapeutic drug
      monitoring of this compound. Total gentamicin is the sum of the concentrations of
      five known congeners C1, C1a, C2, C2a and C2b. To our knowledge, there is so far
      no LC-MS method for quantification of total gentamicin in human serum described
      in literature. METHODS: Sample preparation was based on sample dilution with an
      aqueous internal standard solution followed by protein precipitation. Stable
      derivatives of gentamicin-glycine congeners were prepared by chemical synthesis
      and used as internal standards. The primary calibration material used in this
      assay was characterized by NMR spectroscopy and the pattern of the gentamicin
      congeners was determined. The total gentamicin was reported as the sum of the
      congeners which were quantified individually by LC-MS/MS. RESULTS: The method
      allows the measurement of total gentamicin in human serum and plasma in the
      concentration range of 0.1 to 12.0MUg/ml with an assay imprecision of <=6% CV and
      an assay accuracy between 96% and 114%. LOD and LOQ for the total gentamicin were
      0.04MUg/ml and 0.13MUg/ml, respectively. Comparative measurement of 128 native
      patient samples using this method implemented at two laboratory sites showed an
      excellent agreement. CONCLUSIONS: Validation results proved that this protocol
      describes a robust and reliable method which is suggested as reference
      measurement procedure for the standardization and harmonization of routine assays
      for the quantification of total gentamicin.

PMID- 27871845
TI  - Inter-generational effects of the in vitro maturation technique on pregnancy
      outcomes, early development, and cognition of offspring in mouse model.
AB  - In vitro maturation (IVM) of oocytes has been a highly successful method for
      avoiding the occurrence of severe ovarian hyperstimulation syndrome in some
      patients during in vitro fertilization. However, the safety of the protocol,
      especially the long-term effects, is still an issue of debate. The current study
      is to investigate the long-term effects of IVM on mice through two generations
      and reveal its inter-generational effects as well. The data indicate that the
      rates of embryo resorption and fetal death in the F1 generation were
      significantly increased while the newborn survival rate in the F1 and F2
      generations were significantly decreased in the IVM group. Increased body weights
      in the F1 generation and mouse number per litter in the F2 generation were
      observed in both the IVM and VVM groups; however, no insulin resistance was
      detected. No significant differences were detected in birth defects, organ
      weights, testis histology and sperm motility, estrous cycle, and cognition among
      the IVM, VVM and N mice in either the F1 or F2 generations. Our results suggest
      that mouse IVM can affect pregnancy outcomes throughout two generations. IVM does
      not appear to influence the development and cognition of the offspring throughout
      two generations.

PMID- 27871846
TI  - The oxidant-antioxidant equilibrium, activities of selected lysosomal enzymes and
      activity of acute phase protein in peripheral blood of 18-year-old football
      players after aerobic cycle ergometer test combined with ice-water immersion or
      recovery at room temperature.
AB  - The goal of the study was to evaluate the effect of an aerobic exercise bout
      followed by ice-water immersion or recovery at room temperature on the redox
      state, activities of selected lysosomal enzymes and activity of alpha1
      antitrypsin (AAT) in the blood of healthy sportsmen. Eleven amateur football
      players aged 18 were randomly assigned to two similar 30-min aerobic cycle
      ergometer tests followed by a recovery at room temperature (20  degrees C;
      Experiment 1) or ice-water immersion (3  degrees C, 5 min; Experiment 2).
      Peripheral blood was collected three times during both study experiments: before
      (baseline), as well as 20 and 40 min after the recovery or immersion. The
      concentrations of thiobarbituric acid reactive substances in blood plasma
      (plTBARS) and erythrocytes (erTBARS) were measured. The erythrocytic activities
      of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)
      were also determined. In the blood serum, the activities of acid phosphatase
      (AcP), arylsulphatase (ASA), cathepsin D (CTS D) and AAT were evaluated. The
      activities of AcP, ASA, CTS D and AAT changed similarly during both experiments.
      The GPx activity decreased 40 min after the exercise/recovery compared to the
      baseline activity and was lower than 40 min after the exercise/immersion. The
      exercise followed by the recovery or immersion had no significant effect on the
      serum lysosomal and AAT activities in the studied men. The exercise/recovery
      reduced the hydrogen peroxide concentration in the men's erythrocytes, however
      the exercise/immersion demonstrated the opposite effect.

PMID- 27871847
TI  - Fatty acids composition in erythrocyte membranes of athletes after one and after
      a series of whole body cryostimulation sessions.
AB  - Whole body cryotherapy (WBC) is a treatment often used by athletes as part of
      biological renewal. Despite the large interest in this form therapy there is
      still a lack of information on the effects of WBC on the concentration of fatty
      acids in erythrocyte membranes. Our study aimed at comparing the fatty acids (FA)
      composition of erythrocyte membranes of athletes after one session and after a
      series of sessions of whole body cryostimulation. In our study small changes in
      the level of total cholesterol (decrease) were observed 24 h after a single
      session. After the twelfth session of whole body cryostimulation, the level of
      saturated fatty acids (SFA), mainly palmitic acid (C16:0) and n-3 fatty acid
      eicosapentaenoic (EPA, C20:5n-3) increased almost two-times fold in the red blood
      cell membranes. The level of n-6 polyunsaturated fatty acids (PUFA n-6), mainly
      gamma-linolenic acid (C18:3n-6) as well as trans fatty acids (elaidic acid)
      decreased in the erythrocyte membranes from men after a series of session in a
      cryochamber, when compared to the control sample. The n-3/n-6 FA ratio in the
      erythrocyte membranes was higher after twelfth session in a cryochamber in
      comparison to the control sample. The data obtained during our study will be
      important for further research regarding the biochemistry of lipids in men after
      sessions of whole body cryostimulation.

PMID- 27871848
TI  - Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative
      stress: Involving of mitochondria and energy metabolism.
AB  - Oxidative stress has been demonstrated to be involved in the etiology of several
      neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor,
      has been implicated in promoting several aspects of brain remodeling process.
      Mitochondria may play an important role in controlling fundamental processes in
      neuroplasticity. However, little evidence is available about the effect and the
      potential mechanism of Shh on neurite outgrowth in primary cortical neurons under
      oxidative stress. Here, we revealed that Shh treatment significantly increased
      the viability of cortical neurons in a dose-dependent manner, which was damaged
      by hydrogen peroxide (H2O2). Shh alleviated the apoptosis rate of H2O2-induced
      neurons. Shh also increased neuritogenesis injuried by H2O2 in primary cortical
      neurons. Moreover, Shh reduced the generation of reactive oxygen species (ROS),
      increased the activities of SOD and and decreased the productions of MDA. In
      addition, Shh protected mitochondrial functions, elevated the cellular ATP levels
      and amelioratesd the impairment of mitochondrial complex II activities of
      cortical neurons induced by H2O2. In conclusion, all these results suggest that
      Shh acts as a prosurvival factor playing an essential role to neurite outgrowth
      of cortical neuron under H2O2 -induced oxidative stress, possibly through
      counteracting ROS release and preventing mitochondrial dysfunction and ATP as
      well as mitochondrial complex II activities against oxidative stress.

PMID- 27871849
TI  - CD44 fucosylation on mesenchymal stem cell enhances homing and macrophage
      polarization in ischemic kidney injury.
AB  - The lack of homing ability possibly reduces the healing potential of bone-marrow
      derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on
      MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent
      E-selectin affinity might enhance the homing and regenerative abilities of MSCs.
      Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N
      glycans of CD44 to become HCELL positive, thus interacting with E-selectin on
      injured endothelial cells. HCELL expression facilitated MSC homing in kidneys
      within 24h after injury and reduced lung stasis. An in vitro adhesion assay
      revealed that transfection enhanced the association between MSCs and hypoxic
      endothelial cells. In mice treated with HCELL-positive MSCs, the injured kidneys
      exhibited clusters of homing MSCs, whereas MSCs were rarely observed in mouse
      kidneys treated with HCELL-negative MSCs. Most MSCs were initially localized at
      the renal capsule, and some MSCs later migrated inward between tubules. Most
      homing MSCs were in close contact with inflammatory cells without tubular
      transdifferentiation. Furthermore, HCELL-positive MSCs substantially alleviated
      renal injury, partly by enhancing the polarization of infiltrating macrophages.
      In conclusion, engineering the glycan of CD44 on MSCs through FTVI transfection
      might enhance renotropism and the regenerating ability of MSCs in ischemic kidney
      injury.

PMID- 27871850
TI  - ERalpha inhibited myocardin-induced differentiation in uterine fibroids.
AB  - Uterine fibroids, also known as uterine leiomyomas, are a benign tumor of the
      human uterus and the commonest estrogen-dependent benign tumor found in women.
      Myocardin is an important transcriptional regulator in smooth and cardiac muscle
      development. The role of myocardin and its relationship with ERalpha in uterine
      fibroids have barely been addressed. We noticed that the expression of myocardin
      was markedly reduced in human uterine fibroid tissue compared with corresponding
      normal or adjacent myometrium tissue. Here we reported that myocardin induced the
      transcription and expression of differentiation markers SM22alpha and alpha
      smooth muscle actin (alpha-SMA) in rat primary uterine smooth muscle cells
      (USMCs) and this effect was inhibited by ERalpha. Notably, we showed that,
      ERalpha induced expression of proliferation markers PCNA and ki-67 in rat primary
      USMCs. We also found ERalpha interacted with myocardin and formed complex to bind
      to CArG box and inhibit the SM22alpha promoter activity. Furthermore, ERalpha
      inhibited the transcription and expression of myocardin, and reduced the levels
      of transcription and expression of downstream target SM22alpha, a SMC
      differentiation marker. Our data thus provided important and novel insights into
      how ERalpha and myocardin interact to control the cell differentiation and
      proliferation of USMCs. Thus, it may provide potential therapeutic target for
      uterine fibroids.

PMID- 27871852
TI  - Some pungent arguments against the physico-chemical theories of the origin of the
      genetic code and corroborating the coevolution theory.
AB  - Whereas it is extremely easy to prove that "if the biosynthetic relationships
      between amino acids were fundamental in the structuring of the genetic code, then
      their physico-chemical properties might also be revealed in the genetic code
      table"; it is, on the contrary, impossible to prove that "if the physico-chemical
      properties of amino acids were fundamental in the structuring of the genetic
      code, then the presence of the biosynthetic relationships between amino acids
      should not be revealed in the genetic code". And, given that in the genetic code
      table are mirrored both the biosynthetic relationships between amino acids and
      their physico-chemical properties, all this would be a test that would falsify
      the physico-chemical theories of the origin of the genetic code. That is to say,
      if the physico-chemical properties of amino acids had a fundamental role in
      organizing the genetic code, then we would not have duly revealed the presence -
      in the genetic code - of the biosynthetic relationships between amino acids, and
      on the contrary this has been observed. Therefore, this falsifies the physico
      chemical theories of genetic code origin. Whereas, the coevolution theory of the
      origin of the genetic code would be corroborated by this analysis, because it
      would be able to give a description of evolution of the genetic code more
      coherent with the indisputable empirical observations that link both the
      biosynthetic relationships of amino acids and their physico-chemical properties
      to the evolutionary organization of the genetic code.

PMID- 27871851
TI  - Dual function of Ixr1 in transcriptional regulation and recognition of cisplatin
      DNA adducts is caused by differential binding through its two HMG-boxes.
AB  - Ixr1 is a transcriptional factor involved in the response to hypoxia, which is
      also related to DNA repair. It binds to DNA through its two in-tandem high
      mobility group box (HMG-box) domains. Each function depends on recognition of
      different DNA structures, B-form DNA at specific consensus sequences for
      transcriptional regulation, or distorted DNA, like cisplatin-DNA adducts, for DNA
      repair. However, the contribution of the HMG-box domains in the Ixr1 protein to
      the formation of different protein-DNA complexes is poorly understood. We have
      biophysically and biochemically characterized these interactions with specific
      DNA sequences from the promoters regulated by Ixr1, or with cisplatin-DNA
      adducts. Both HMG-boxes are necessary for transcriptional regulation, and they
      are not functionally interchangeable. The in-tandem arrangement of their HMG
      boxes is necessary for functional folding and causes sequential cooperative
      binding to specific DNA sequences, with HMG-box A showing a higher contribution
      to DNA binding and bending than the HMG-box B. Binding of Ixr1 HMG boxes to
      specific DNA sequences is entropy driven, whereas binding to platinated DNA is
      enthalpy driven for HMG-box A and entropy driven for HMG-box B. This is the first
      proof that HMG-box binding to different DNA structures is associated with
      predictable thermodynamic differences. Based on our study, we present a model to
      explain the dual function of Ixr1 in the regulation of gene expression and
      recognition of distorted DNA structures caused by cisplatin treatment.

PMID- 27871853
TI  - Nur77 downregulation triggers pulmonary artery smooth muscle cell proliferation
      and migration in mice with hypoxic pulmonary hypertension via the Axin2-beta
      catenin signaling pathway.
AB  - Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized
      by remodeling of the pulmonary vasculature, including marked proliferation and
      reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of
      the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological
      events, such as cell apoptosis, proliferation, inflammation, and metabolism.
      Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily)
      has recently been reported to be as a beneficial agent in the treatment of
      cardiovascular and metabolic diseases. In the present study, we investigated the
      effects of NR4A on human PASMCs function in vitro and determined the underlying
      mechanisms. We found a robust expression of NR4A receptors in lung tissues of PAH
      patients and hypoxic mice but a highly significant downregulation within
      pulmonary arteries (PAs) as assessed by quantitative polymerase chain reaction,
      immunoblotting, and immunohistochemistry. In vitro, NR4A receptors were found
      significantly decreased in PASMCs derived from PAH patients. To explore the
      pathological effects of decreased Nur77 in PASMCs, PASMCs were transduced with
      siRNA against Nur77. The siRNA-mediated knockdown of Nur77 significantly
      augmented PASMCs proliferation and migration. In contrast, Nur77 overexpression
      prevented PASMCs from proliferation and migration. Mechanistically,
      overexpression of Axis inhibition protein 2 (Axin2) or inhibition of beta-catenin
      signaling was shown to be responsible for Nur77 knockdown-induced proliferation
      of PASMCs. Following hypoxia-induced angiogenesis of the pulmonary artery in
      C57BL/6 mice, small-molecule Nur77 agonists-Octaketide Cytosporone B (Csn-B) can
      significantly decreased thickness of vascular wall and markedly attenuated the
      development of chronic hypoxia-induced PAH in vivo. Therefore, reconstitution of
      Nur77 levels represents a promising therapeutic option to prevent vascular
      remodeling processes.

PMID- 27871855
TI  - Histone deacetylase 1 (HDAC1) regulates retinal development through a PAX6
      dependent pathway.
AB  - Cell fate determination is tightly controlled by the expression of transcription
      factors and gene regulatory networks. PAX6 is a transcription factor containing a
      DNA-binding paired-box domain and homeobox domain that plays a key role in the
      development of the eye, brain, and pancreas. Here, we showed that histone
      deacetyltransferase 1 (HDAC1) is a novel binding partner of PAX6 in newborn mouse
      retinas. We also showed that HDAC1 specifically binds to the paired and
      transactivation domains of PAX6, and these physical interactions were required
      for effective repression of PAX6 transcriptional activity during retinal
      development. Furthermore, HDAC1 preferentially regulates the transcriptional
      activity of PAX6 when it binds to paired-domain (P6CON and chimeric pCON/P3) PAX6
      responsive elements compared to homeodomain (pP3) PAX6 responsive elements. The
      repressive effect of HDAC1 on the transcriptional activity of PAX6 was reversed
      by knockdown of HDAC1 or treatment with an HDAC inhibitor, TSA. Taken together,
      these results show that HDAC1 binds PAX6 and that protein-protein interaction
      leads to transcriptional repression of PAX6 target genes during mouse retinal
      development.

PMID- 27871854
TI  - Rate adaptive pacing in an intracardiac pacemaker.
AB  - BACKGROUND: The Micra transcatheter pacemaker was designed to have similar
      functionality to conventional transvenous VVIR pacing systems. It provides rate
      adaptive pacing using a programmable 3-axis accelerometer designed to detect
      patient activity in the presence of cardiac motion. OBJECTIVE: The purpose of
      this study was to evaluate the system's performance during treadmill tests to
      maximum exertion in a subset of patients within the Micra Transcatheter Pacing
      Study. METHODS: Patients underwent treadmill testing at 3 or 6 months postimplant
      with algorithm programming at physician discretion. Normalized sensor rate (SenR)
      relative to the programmed upper sensor rate was modeled as a function of
      normalized workload in metabolic equivalents (METS) relative to maximum METS
      achieved during the test. A normalized METS and SenR were determined at the end
      of each 1-minute treadmill stage. The proportionality of SenR to workload was
      evaluated by comparing the slope from this relationship to the prospectively
      defined tolerance margin (0.65-1.35). RESULTS: A total of 69 treadmill tests were
      attempted by 42 patients at 3 and 6 months postimplant. Thirty tests from 20
      patients who completed >=4 stages with an average slope of 0.86 (90% confidence
      interval 0.77-0.96) confirmed proportionality to workload. On an individual test
      basis, 25 of 30 point estimates (83.3%) had a normalized slope within the defined
      tolerance range (range 0.46-1.08). CONCLUSION: Accelerometer-based rate adaptive
      pacing was proportional to workload, thus confirming rate adaptive pacing
      commensurate to workload is achievable with an entirely intracardiac pacing
      system.

PMID- 27871856
TI  - Will cardiac optogenetics find the way through the obscure angles of heart
      physiology?
AB  - Optogenetics is a technique exploded in the last 10 years, which revolutionized
      several areas of biological research. The brightest side of this technology is
      the use of light to modulate non-invasively, with high spatial resolution and
      millisecond time scale, excitable cells genetically modified to express light
      sensitive microbial ion channels (opsins). Neuroscience has first benefited from
      such fascinating strategy, in intact organisms. By shining light to specific
      neuronal subpopulations, optogenetics allowed unearth the mechanisms involved in
      cell-to-cell communication within the context of intact organs, such as the
      brain, formed by complex neuronal circuits. More recently, scientists looked at
      optogenetics as a tool to answer some of the questions, remained in the dark, of
      cardiovascular physiology. In this review, we focus on the application of
      optogenetics in the study of the heart, a complex multicellular organ, homing
      different populations of excitable cells, spatially and functionally
      interconnected. Moving from the first proof-of-principle works, published in
      2010, to the present time, we discuss the in vitro and in vivo applications of
      optogenetics for the study of electrophysiology of the different cardiac cell
      types, and for the dissection of cellular mechanisms underlying arrhythmias. We
      also present how molecular biology and technology foster the evolution of cardiac
      optogenetics, with the aim to further our understanding of fundamental questions
      in cardiac physiology and pathology. Finally, we confer about the therapeutic
      potential of such biotechnological strategy for the treatment of heart rhythm
      disturbances (e.g. cardiac pacing, cardioversion).

PMID- 27871857
TI  - Bmi-1 plays a critical role in the protection from acute tubular necrosis by
      mobilizing renal stem/progenitor cells.
AB  - The regeneration of injured tubular cell occurs primarily from intrinsic renal
      stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular
      necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal,
      differentiation and aging of multiple adult stem cells and progenitor cells. Bmi
      1 was rapidly elevated in the induction of adult kidney regeneration by renal
      injury. To determine whether Bmi-1 maintained mobilization of RSCs in the
      protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild
      type (WT) and Bmi-1-deficient (Bmi-1-/-) mice. Their ATN phenotypes were
      analyzed; CD24 and CD133 double positive (CD24+CD133+) cells were measured; and
      the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected.
      We found that CD24+CD133+ RSCs were mobilized in WT ATN mice with the increased
      expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and
      necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and
      immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a
      critical role in the protection from ATN by maintaining mobilization of RSCs and
      would be a novel therapeutic target for preventing the progression of ATN.

PMID- 27871858
TI  - Adipokine CTRP6 improves PPARgamma activation to alleviate angiotensin II-induced
      hypertension and vascular endothelial dysfunction in spontaneously hypertensive
      rats.
AB  - Angiotensin II (AngII) is the most important component of angiotensin, which has
      been regarded as a major contributor to the incidence of hypertension and
      vascular endothelial dysfunction. The adipocytokine C1q/TNF-related protein 6
      (CTRP6) was recently reported to have multiple protective effects on cardiac and
      cardiovascular function. However, the exact role of CTRP6 in the progression of
      AngII induced hypertension and vascular endothelial function remains unclear.
      Here, we showed that serum CTRP6 content was significantly downregulated in SHRs,
      accompanied by a marked increase in arterial systolic pressure and serum AngII,
      CRP and ET-1 content. Then, pcDNA3.1-mediated CTRP6 delivery or CTRP6 siRNA was
      injected into SHRs. CTRP6 overexpression caused a significant decrease in AngII
      expression and AngII-mediated hypertension and vascular endothelial inflammation.
      In contrast, CTRP6 knockdown had the opposite effect to CTRP6 overexpression.
      Moreover, we found that CTRP6 positively regulated the activation of the ERK1/2
      signaling pathway and the expression of peroxisome proliferator-activated
      receptor gamma (PPARgamma), a recently proven negative regulator of AngII, in the
      brain and vascular endothelium of SHRs. Finally, CTRP6 was overexpressed in
      endothelial cells, and caused a significant increase in PPARgamma activation and
      suppression in AngII-mediated vascular endothelial dysfunction and apoptosis. The
      effect of that could be rescued by the ERK inhibitor PD98059. In contrast,
      silencing CTRP6 suppressed PPARgamma activation and exacerbated AngII-mediated
      vascular endothelial dysfunction and apoptosis. In conclusion, CTRP6 improves
      PPARgamma activation and alleviates AngII-induced hypertension and vascular
      endothelial dysfunction.

PMID- 27871859
TI  - Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to
      cisplatin-induced apoptosis.
AB  - Emerging evidence indicates that beta-galactoside-alpha2,3-sialyltransferase III
      (ST3Gal3) involves in development, inflammation, neoplastic transformation, and
      metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance
      remains elusive. Herein, we investigated the functional effects of ST3Gal3 in
      cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3
      mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that
      have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are
      resistant to cisplatin, comparing to SKOV3 cells that have a lower level of
      ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the
      expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used
      in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate
      ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown
      in cancer cell lines using FACS analysis. The number of apoptotic cells was much
      higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by
      treating cells with higher dosage of cisplatin in comparison to control cells.
      Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8
      and caspase 3 proteins increased, which was more obvious in cells treated with
      both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown
      synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells.
      Taken together, these results uncover an alternative mechanism of cisplatin
      resistance through ST3Gal3 and open a window for effective prevention of
      chemoresistance and relapse of ovarian cancer by targeting ST3Gal3.

PMID- 27871860
TI  - In vitro reconstitution of breast cancer heterogeneity with multipotent cancer
      stem cells using small molecules.
AB  - A small fraction of tumor cells are thought to possess the potential for both
      multiple-lineage differentiation and self-renewal, which underlies the cancer
      stem cell hypothesis. However, the differentiation mechanisms of these cells have
      not been elucidated due to a lack of appropriate culture methods. Here, we
      established a culture condition for maintaining multipotent tumor cells from rat
      breast tumors using 4 small molecules. Cultured tumor cells in this condition
      retained their intrinsic myoepithelial features, expressing p63 and CK14 and
      vimentin. In a xenograft model, the p63-expressing cells formed epithelial tumors
      containing glandular, squamous and sebaceous compartments. Upon withdrawal of the
      small molecules, p63 and CK14 expression was lost, with concurrent increase in
      expression of mesenchymal markers. These transited cells acquired drug resistance
      and invasiveness and showed massive sarcomatoid tumorigenicity. Epithelial
      features could not be recovered by re-exposure to the small molecules in the
      transited cells. Here, we have identified multipotent cancer cells within primary
      mammary tumors and demonstrated that their plasticity is maintained by the small
      molecules.

PMID- 27871861
TI  - The role of steroids in the prediction of affective disorders in adult men.
AB  - OBJECTIVE: Anxiety and mood disorders (AMD) are the most frequent mental
      disorders in the human population. They have recently shown increasing
      prevalence, and commonly disrupt personal and working lives. The aim of our study
      was to analyze the spectrum of circulating steroids in order to discover
      differences that could potentially be markers of affective depression or anxiety,
      and identify which steroids could be a predictive component for these diseases.
      METHODS: We studied the steroid metabolome including 47 analytes in 20 men with
      depression (group D), 20 men with anxiety (group AN) and 30 healthy controls.
      OPLS and multivariate regression models were used for statistical analysis.
      RESULTS: Discrimination of group D from controls by the OPLS method was absolute,
      as was group AN from controls (sensitivity=1.000 (0.839, 1.000),
      specificity=1.000 (0.887, 1.000)). Relatively good predictivity was also found
      for discrimination between group D from AN (sensitivity=0.850 (0.640, 0.948),
      specificity=0.900 (0.699, 0.972)). CONCLUSION: Selected circulating steroids,
      including those that are neuroactive and neuroprotective, can be useful tools for
      discriminating between these affective diseases in adult men.

PMID- 27871863
TI  - Muscular system in interna of Peltogaster paguri (Rhizocephala: Peltogastridae).
AB  - Rhizocephalan parasites have a peculiar life cycle, and their adults lost almost
      all traits found usually in Crustacea. Despite some data on anatomy and
      ultrastructure of interna of Peltogastridae, some crucial aspects of morphology
      are still unknown. For example, there is only one mentioning of myocytes found in
      interna of Rhizocephalans (Sacculina carcini). So we aimed at studying the
      muscular system of the interna of Peltogaster paguri using serial histological
      sectioning and fluorescent staining (TRITC-labeled phalloidin) with confocal
      microscopy. Within the wall of the main trunk we found striated muscular fibers.
      The majority of these fibers form a unidirectional single spiral. There are
      additional small fibers that connect the coils of the large spiral. The density
      of muscular fibers is highest near the externa stalk, and the number of muscle
      fibers decreases towards the distal part of the main trunk. We suggest that such
      a muscular system could provide peristaltic movements of the main trunk and the
      transport of nutrients through the interna.

PMID- 27871864
TI  - Review of developmental origins of health and disease publications in
      environmental epidemiology.
AB  - The Developmental Origins of Health and Disease (DOHaD) scientific field
      investigates the influence of early life environmental stressors on later life
      health outcomes. Environmental chemical exposures are a particular focus area
      within this field. Although the DOHaD hypothesis originated in the 1990s, the
      data evaluating this hypothesis in environmental epidemiology has not been
      comprehensively summarized. We conducted a scoping literature review to describe
      the human evidence for the DOHaD hypothesis and to identify, 1) where there may
      be reasonable data to draw conclusions, and 2) areas warranting further research.
      Using PubMed and Web of Science we identified 425 publications through 2014 that
      met our criteria for evaluating the DOHaD hypothesis in environmental
      epidemiology. These publications covered 60 different chemicals. The majority of
      publications focused on neurological/cognitive outcomes, followed by cancer, and
      respiratory outcomes. We note areas ready for more detailed review, those
      requiring more data and ideas for future directions.

PMID- 27871865
TI  - Iterative reconstruction of radially-sampled 31P bSSFP data using prior
      information from 1H MRI.
AB  - The purpose of this study is to improve direct phosphorus (31P) MR imaging.
      Therefore, 3D density-adapted radially-sampled balanced steady-state free
      precession (bSSFP) sequences were developed and an iterative approach exploiting
      additional anatomical information from hydrogen (1H) data was evaluated. Three
      healthy volunteers were examined at B0=7T in order to obtain the spatial
      distribution of the phosphocreatine (PCr) intensities in the human calf muscle
      with a nominal isotropic resolution of 10mm in an acquisition time of 10min.
      Three different bSSFP gradient schemes were investigated. The highest signal-to
      noise ratio (SNR) was obtained for a scheme with two point-reflected density
      adapted gradients. Furthermore, the conventional reconstruction based on a
      gridding algorithm was compared to an iterative method using an 1H MRI constraint
      in terms of a segmented binary mask, which comprises prior knowledge. The
      parameters of the iterative approach were optimized and evaluated by simulations
      featuring 31P MRI parameters. Thereby, partial volume effects as well as Gibbs
      ringing artifacts could be reduced. In conclusion, the iterative reconstruction
      of 31P bSSFP data using an 1H MRI constraint is appropriate for investigating
      regions where sharp tissue boundaries occur and leads to images that represent
      the real PCr distributions better than conventionally reconstructed images.

PMID- 27871866
TI  - Effects of the GluN2B-NMDA receptor antagonist Ro 25-6981 on two types of
      behavioral flexibility in rats.
AB  - Recent evidence has implicated N-methyl-d-aspartate receptors (NMDARs) in several
      aspects of learning and behavioral flexibility in rodents. Here, we examined the
      effects of treatment with Ro 25-6981, a selective antagonist of NMDARs containing
      GluN2B subunits, on two types of behavioral flexibility in rats, spatial reversal
      learning and set-shifting (spatial vs. motor strategy). To examine spatial
      reversal learning, rats were trained to swim to a hidden platform in a water maze
      over four days. On the following day, the platform was moved to a new location in
      the maze. Administration of Ro 25-6981 (10mg/kg) selectively impaired the early
      phase of reversal learning, but all rats learned to navigate to the new platform
      location over 12 trials. To examine set-shifting, independent groups of rats were
      trained to either swim to a fixed location (spatial strategy) or use a motor
      response (e.g., "turn left"; motor strategy) to find a hidden escape platform in
      a cross-shaped water maze apparatus; after task acquisition, rats were trained on
      the second, novel strategy (set-shift) following treatment with either Ro 25-6981
      (10mg/kg) or saline. Administration of Ro 25-6981 had no effect on the ability of
      rats to perform the set-shift and use the new strategy to locate the escape
      platform. These results suggest that, in rats, spatial reversal learning, but not
      set-shifting, is sensitive to Ro-25-6981 treatment. Thus, NMDARs-GluN2B signaling
      may play a selective role in some forms of behavioral plasticity, particularly
      for situations involving the updating of information in the spatial domain.

PMID- 27871867
TI  - Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice.
AB  - Noni (Morinda citrifolia) leaf and fruit are used as food and medicine. This
      report compares the chronic toxicity of Noni fruit and edible leaf water extracts
      (two doses each) in female mice. The 6 months study showed the fruit extract
      produced chronic toxicity effects at the high dose of 2 mg/ml drinking water,
      evidenced through deteriorated liver histology (hepatocyte necrosis), reduced
      liver length, increased liver injury marker AST (aspartate aminotransferase) and
      albumin reduction, injury symptoms (hypoactivity, excessive grooming, sunken eyes
      and hunched posture) and 40% mortality within 3 months. This hepatotoxicity
      results support the six liver injury reports in humans which were linked to
      chronic noni fruit juice consumption. Both doses of the leaf extracts
      demonstrated no observable toxicity. The hepatotoxicity effects of the M.
      citrifolia fruit extract in this study is unknown and may probably be due to the
      anthraquinones in the seeds and skin, which had potent quinone reductase inducer
      activity that reportedly was 40 times more effective than l-sulforaphane. This
      report will add to current data on the chronic toxicity cases of Morinda
      citrifolia fruit. No report on the chronic toxicity of Morinda citrifolia fruit
      in animal model is available for comparison.

PMID- 27871869
TI  - Use of read-across to simplify the toxicological assessment of a complex mixture
      of lysimeter leachate metabolites on the basis of chemical similarity and ADME
      behavior.
AB  - This paper describes the further development of a read-across approach applicable
      to the toxicological assessment of structurally-related xenobiotic metabolites.
      The approach, which can be applied in the absence of definitive identification of
      all the individual metabolites, draws on the use of chemical descriptors and
      multi-variate statistical analysis to define a composite "chemical space" and to
      classify and characterize closely-related subgroups within this. In this example,
      consideration of the descriptors driving grouping, combined with empirical
      evidence for lack of significant further biotransformation of metabolites, leads
      to the conclusion that, in the absence of any specific structural alerts, the
      relative toxicity of metabolites within a single grouping will be determined by
      their relative systemic exposure as described by their ADME characteristics. The
      in vivo testing of a smaller number of exemplars, selected to have representative
      ADME properties for each grouping, is sufficient, therefore, to evaluate the
      toxicity of the remainder. The approach is exemplified using the metabolites of
      the herbicide S-metolachlor, detected in the leachate of a soil lysimeter.

PMID- 27871868
TI  - Quantitative risk assessment for skin sensitization: Success or failure?
AB  - Skin sensitization is unique in the world of toxicology. There is a combination
      of reliable, validated predictive test methods for identification of skin
      sensitizing chemicals, a clearly documented and transparent approach to risk
      assessment, and effective feedback from dermatology clinics around the world
      delivering evidence of the success or failure of the hazard identification/risk
      assessment/management process. Recent epidemics of contact allergy, particularly
      to preservatives, have raised questions of whether the safety/risk assessment
      process is working in an optimal manner (or indeed is working at all!). This
      review has as its focus skin sensitization quantitative risk assessment (QRA).
      The core toxicological principles of QRA are reviewed, and evidence of use and
      misuse examined. What becomes clear is that skin sensitization QRA will only
      function adequately if two essential criteria are met. The first is that QRA is
      applied rigourously, and the second is that potential exposure to the sensitizing
      substance is assessed adequately. This conclusion will come as no surprise to any
      toxicologist who appreciates the basic premise that "risk = hazard x exposure".
      Accordingly, use of skin sensitization QRA is encouraged, not least because the
      essential feedback from dermatology clinics can be used as a tool to refine QRA
      in situations where this risk assessment tool has not been properly used.

PMID- 27871862
TI  - A users guide to HPA axis research.
AB  - Glucocorticoid hormones (cortisol and corticosterone - CORT) are the effector
      hormones of the hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine system.
      CORT is a systemic intercellular signal whose level predictably varies with time
      of day and dynamically increases with environmental and psychological stressors.
      This hormonal signal is utilized by virtually every cell and physiological system
      of the body to optimize performance according to circadian, environmental and
      physiological demands. Disturbances in normal HPA axis activity profiles are
      associated with a wide variety of physiological and mental health disorders.
      Despite numerous studies to date that have identified molecular, cellular and
      systems-level glucocorticoid actions, new glucocorticoid actions and clinical
      status associations continue to be revealed at a brisk pace in the scientific
      literature. However, the breadth of investigators working in this area poses
      distinct challenges in ensuring common practices across investigators, and a full
      appreciation for the complexity of a system that is often reduced to a single
      dependent measure. This Users Guide is intended to provide a fundamental overview
      of conceptual, technical and practical knowledge that will assist individuals who
      engage in and evaluate HPA axis research. We begin with examination of the
      anatomical and hormonal components of the HPA axis and their physiological range
      of operation. We then examine strategies and best practices for systematic
      manipulation and accurate measurement of HPA axis activity. We feature use of
      experimental methods that will assist with better understanding of CORT's
      physiological actions, especially as those actions impact subsequent brain
      function. This research approach is instrumental for determining the mechanisms
      by which alterations of HPA axis function may contribute to pathophysiology.

PMID- 27871870
TI  - Carcinogenic risk of emerging persistent organic pollutant perfluorooctane
      sulfonate (PFOS): A proposal of classification.
AB  - : Perfluoroalkyls are stable synthetic chemicals, able to repel oils, fats and
      water. These compounds have been used in the manufacturing of products such as
      Teflon(r), lubricants, paints, fire-fighting foams, coatings for pans, carpets,
      clothes, and paperboard for packaging, among others. It is believed that
      populations are exposed constantly to them. Its regulation in the world is under
      development and several controversies are in the course of litigation. One
      occupational study shows bladder cancer risk. This paper intends to review
      scientific information on the most critical perfluoroalkyl compound and proposes
      a procedure to get a cancer-risk categorization which PFOS can cause to
      populations. METHODS: As a guiding axis, we used the IARC process for developing
      monographs of carcinogenic risks. We used the SIGN guides for evaluating the
      quality of studies in human populations; and finally, we used the Squire method
      for evaluating studies in laboratory animals. Inadequate evidence of
      carcinogenicity was found in human studies mainly due to chance, threshold effect
      and confounders. In experimental animal studies, inadequate evidence of
      carcinogenicity was found in view of the number of affected species, different
      types of neoplasms, dose-response relationship and genotoxicity found in in-vivo
      and in-vitro studies. In this proposal, we concluded that cancer risk for PFOS,
      according to the IARC method, is not classifiable as carcinogenic to humans
      (group 3).

PMID- 27871871
TI  - Paleoparasitological analysis of the extinct Myotragus balearicus Bate 1909
      (Artiodactyla, Caprinae) from Mallorca (Balearic Islands, Western Mediterranean).
AB  - Myotragus balearicus (Artiodactyla, Caprinae) is an extinct caprine endemic of
      the Eastern Balearic Islands or Gymnesics (i.e., Mallorca, Menorca and
      surrounding islets, Western Mediterranean Sea). In spite of its small size, c.
      50cm height at the shoulder, it was the largest mammal inhabiting these islands
      until the human arrival, and it had peculiar short legs and frontal vision. It
      disappeared between 2830 and 2210calBCE. The coprolites here studied were
      recovered from Cova Estreta, in Pollenca, Mallorca. The samples were subjected to
      microscopic examination and enzyme-linked immunosorbent assays (ELISA) for E.
      histolytica/E. dispar, Giardia intestinalis and Cryptosporidium parvum. This
      study provides new paleoparasitological data from an extinct animal species of
      the Holocene period. The microscopy revealed one sample containing uninucleated
      cyst of Entamoeba sp., whereas ELISA detected nine positive samples for
      Cryptosporidium sp. The finding of these protozoans can help in the discussion of
      its extinction cause and demonstrates the antiquity and the evolutionary history
      of host-parasite relationships between protozoa and caprines since the Messinian.

PMID- 27871873
TI  - iTRAQ-based proteomic analysis of defence responses triggered by the necrotrophic
      pathogen Rhizoctonia solani in cotton.
AB  - : The soil-borne necrotrophic pathogen fungus Rhizoctonia solani is destructive,
      causing disease in various important crops. To date, little is known about the
      host defence mechanism in response to invasion of R. solani. Here, an iTRAQ-based
      proteomic analysis was employed to investigate pathogen-responsive proteins in
      the disease tolerant/resistant cotton cultivar CRI35. A total of 174
      differentially accumulated proteins (DAPs) were identified after inoculation of
      cotton plants with R. solani. Functional categorization analysis indicated that
      these DAPs can be divided into 12 subclasses. Notably, a large portion of DAPs
      are known to function in reactive oxygen species (ROS) metabolism and the
      expression of several histone-modifying and DNA methylating proteins were
      significantly induced upon challenge with the fungus, indicating that the redox
      homeostasis and epigenetic regulation are important for cotton defence against
      the pathogen. Additionally, the expression of proteins involved in
      phenylpropanoid biosynthesis was markedly changed in response to pathogen
      invasion, which may reflect a particular contribution of secondary metabolism in
      protection against the fungal attack in cotton. Together, our results indicate
      that the defence response of cotton plants to R. solani infection is active and
      multifaceted and involves the induction of proteins from various innate immunity
      related pathways. SIGNIFICANCE: Cotton damping-off is a destructive disease
      caused by the necrotrophic fungus Rhizoctonia solani. To date, the host defence
      mechanism involved in the disease protection remains largely unknown. Here, we
      reported the first proteomic analysis on cotton immune responses against R.
      solani infection. Employing iTRAQ technique, we obtained a total of 174
      differentially accumulated proteins (DAPs) that can be classified into 12
      functional groups. Further analysis indicated that ROS homeostasis, epigenetic
      regulation and phenylpropanoid biosynthesis were tightly associated with the
      innate immune responses against R. solani infection in cotton. The obtained data
      provide not only important information for understanding the molecular mechanism
      involved in plant-R. solani interaction but also application clues for genetic
      breeding of crops with improved R. solani resistance.

PMID- 27871872
TI  - Biotechnological production of aromatic compounds of the extended shikimate
      pathway from renewable biomass.
AB  - Aromatic chemicals that contain an unsaturated ring with alternating double and
      single bonds find numerous applications in a wide range of industries, e.g. paper
      and dye manufacture, as fuel additives, electrical insulation, resins,
      pharmaceuticals, agrochemicals, in food, feed and cosmetics. Their chemical
      production is based on petroleum (BTX; benzene, toluene, and xylene), but they
      can also be obtained from plants by extraction. Due to petroleum depletion,
      health compliance, or environmental issues such as global warming, the
      biotechnological production of aromatics from renewable biomass came more and
      more into focus. Lignin, a complex polymeric aromatic molecule itself, is a
      natural source of aromatic compounds. Many microorganisms are able to catabolize
      a plethora of aromatic compounds and interception of these pathways may lead to
      the biotechnological production of value-added aromatic compounds which will be
      discussed for Corynebacterium glutamicum. Biosynthesis of aromatic amino acids
      not only gives rise to l-tryptophan, L-tyrosine and l-phenylalanine, but also to
      aromatic intermediates such as dehydroshikimate or chorismate from which value
      added aromatic compounds can be derived. In this review, we will summarize recent
      strategies for the biotechnological production of aromatic and related compounds
      from renewable biomass by Escherichia coli, Pseudomonas putida, C. glutamicum and
      Saccharomyces cerevisiae. In particular, we will focus on metabolic engineering
      of the extended shikimate pathway.

PMID- 27871874
TI  - Functional and immuno-reactive characterization of a previously undescribed
      peptide from the venom of the scorpion Centruroides limpidus.
AB  - A previously undescribed toxic peptide named Cl13 was purified from the venom of
      the Mexican scorpion Centruroides limpidus. It contains 66 amino acid residues,
      including four disulfide bonds. The physiological effects assayed in 7 different
      subtypes of voltage gated Na+-channels, showed that it belongs to the beta
      scorpion toxin type. The most notorious effects were observed in subtypes Nav1.4,
      Nav1.5 and Nav1.6. Although having important sequence similarities with two other
      lethal toxins from this scorpion species (Cll1m and Cll2), the recently developed
      single chain antibody fragments (scFv) of human origin were not capable of
      protecting against Cl13. At the amino acid sequence level, in 3 stretches of
      peptide Cl13 (positions 7-9, 30-38 and 62-66) some differences with respect to
      other similar toxins are observed. Some of these differences coincide with
      contact points with the human antibody fragments.

PMID- 27871875
TI  - Pyruvate dehydrogenase has a major role in mast cell function, and its activity
      is regulated by mitochondrial microphthalmia transcription factor.
AB  - BACKGROUND: We have recently observed that oxidative phosphorylation-mediated ATP
      production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is
      the main regulator of the Krebs cycle and is located upstream of the electron
      transport chain. However, the role of PDH in mast cell function has not been
      described. Microphthalmia transcription factor (MITF) regulates the development,
      number, and function of mast cells. Localization of MITF to the mitochondria and
      its interaction with mitochondrial proteins has not been explored. OBJECTIVE: We
      sought to explore the role played by PDH in mast cell exocytosis and to determine
      whether MITF is localized in the mitochondria and involved in regulation of PDH
      activity. METHODS: Experiments were performed in vitro by using human and mouse
      mast cells, as well as rat basophil leukemia cells, and in vivo in mice. The
      effect of PDH inhibition on mast cell function was examined. PDH interaction with
      MITF was measured before and after immunologic activation. Furthermore,
      mitochondrial localization of MITF and its effect on PDH activity were
      determined. RESULTS: PDH is essential for immunologically mediated degranulation
      of mast cells. After activation, PDH is serine dephosphorylated. In addition, for
      the first time, we show that MITF is partially located in the mitochondria and
      interacts with PDH. This interaction is dependent on the phosphorylation state of
      PDH. Furthermore, mitochondrial MITF regulates PDH activity. CONCLUSION: The
      association of mitochondrial MITF with PDH emerges as an important regulator of
      mast cell function. Our findings indicate that PDH could arise as a new target
      for the manipulation of allergic diseases.

PMID- 27871877
TI  - Clinical potential for imaging in patients with asthma and other lung disorders.
AB  - The ability of lung imaging to phenotype patients, determine prognosis, and
      predict response to treatment is expanding in clinical and translational
      research. The purpose of this perspective is to describe current imaging
      modalities that might be useful clinical tools in patients with asthma and other
      lung disorders and to explore some of the new developments in imaging modalities
      of the lung. These imaging modalities include chest radiography, computed
      tomography, lung magnetic resonance imaging, electrical impedance tomography,
      bronchoscopy, and others.

PMID- 27871876
TI  - Disaggregating asthma: Big investigation versus big data.
AB  - We are facing a major challenge in bridging the gap between identifying subtypes
      of asthma to understand causal mechanisms and translating this knowledge into
      personalized prevention and management strategies. In recent years, "big data"
      has been sold as a panacea for generating hypotheses and driving new frontiers of
      health care; the idea that the data must and will speak for themselves is fast
      becoming a new dogma. One of the dangers of ready accessibility of health care
      data and computational tools for data analysis is that the process of data mining
      can become uncoupled from the scientific process of clinical interpretation,
      understanding the provenance of the data, and external validation. Although
      advances in computational methods can be valuable for using unexpected structure
      in data to generate hypotheses, there remains a need for testing hypotheses and
      interpreting results with scientific rigor. We argue for combining data- and
      hypothesis-driven methods in a careful synergy, and the importance of carefully
      characterized birth and patient cohorts with genetic, phenotypic, biological, and
      molecular data in this process cannot be overemphasized. The main challenge on
      the road ahead is to harness bigger health care data in ways that produce
      meaningful clinical interpretation and to translate this into better diagnoses
      and properly personalized prevention and treatment plans. There is a pressing
      need for cross-disciplinary research with an integrative approach to data
      science, whereby basic scientists, clinicians, data analysts, and epidemiologists
      work together to understand the heterogeneity of asthma.

PMID- 27871878
TI  - Large-scale gene expression profiling reveals distinct type 2 inflammatory
      patterns in chronic rhinosinusitis subtypes.

PMID- 27871879
TI  - Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating
      sirtuin 1 expression.
AB  - BACKGROUND & AIMS: Aging is known to exacerbate the progression of alcoholic
      liver disease (ALD), but the underlying mechanisms remain obscure. The aim of
      this study was to use a chronic plus binge ethanol feeding model in mice to
      evaluate the effects of aging on alcohol-induced liver injury. METHODS: C57BL/6
      mice were subjected to short-term (10days) ethanol plus one binge or long-term
      (8weeks) ethanol plus multiple binges of ethanol. Liver injury and fibrosis were
      determined. Hepatic stellate cells (HSCs) were isolated and used in in vitro
      studies. RESULTS: Middle-aged (12-14months) and old-aged (>16months) mice were
      more susceptible to liver injury, inflammation, and oxidative stress induced by
      short-term plus one binge or long-term plus multiple binges of ethanol feeding
      when compared to young (8-12weeks) mice. Long-term plus multiple binges of
      ethanol feeding induced greater liver fibrosis in middle-aged mice than that in
      young mice. Hepatic expression of sirtuin 1 (SIRT1) protein was downregulated in
      the middle-aged mice compared to young mice. Restoration of SIRT1 expression via
      the administration of adenovirus-SIRT1 vector ameliorated short-term plus binge
      ethanol-induced liver injury and fibrosis in middle-aged mice. HSCs isolated from
      middle-aged mice expressed lower levels of SIRT1 protein and were more
      susceptible to spontaneous activation in in vitro culture than those from young
      mice. Overexpression of SIRT1 reduced activation of HSCs from middle-aged mice in
      vitro with downregulation of PDGFR-alpha and c-Myc, while deletion of SIRT1
      activated HSCs isolated from young mice in vitro. Finally, HSC-specific SIRT1
      knockout mice were more susceptible to long-term chronic-plus-multiple binges of
      ethanol-induced liver fibrosis with upregulation of PDGFR-alpha expression.
      CONCLUSIONS: Aging exacerbates ALD in mice through the downregulation of SIRT1 in
      hepatocytes and HSCs. Activation of SIRT1 may serve as a novel target for the
      treatment of ALD. LAY SUMMARY: Aged mice are more susceptible to alcohol-induced
      liver injury and fibrosis, which is, at least in part, due to lower levels of
      sirtuin 1 protein in hepatocytes and hepatic stellate cells. Our findings suggest
      that sirtuin 1 activators may have beneficial effects for the treatment of
      alcoholic liver disease in aged patients.

PMID- 27871880
TI  - Abscisic acid enhances glucose disposal and induces brown fat activity in
      adipocytes in vitro and in vivo.
AB  - Abscisic acid (ABA) is a plant hormone also present in animals, where it is
      involved in the regulation of innate immune cell function and of glucose
      disposal, through its receptor LANCL2. ABA stimulates glucose uptake by myocytes
      and pre-adipocytes in vitro and oral ABA improves glycemic control in rats and in
      healthy subjects. Here we investigated the role of the ABA/LANCL2 system in the
      regulation of glucose uptake and metabolism in adipocytes. Silencing of LANCL2
      abrogated both the ABA- and insulin-induced increase of glucose transporter-4
      expression and of glucose uptake in differentiated 3T3-L1 murine adipocytes;
      conversely, overexpression of LANCL2 enhanced basal, ABA- and insulin-stimulated
      glucose uptake. As compared with insulin, ABA treatment of adipocytes induced
      lower triglyceride accumulation, CO2 production and glucose-derived fatty acid
      synthesis. ABA per se did not induce pre-adipocyte differentiation in vitro, but
      stimulated adipocyte remodeling in terminally differentiated cells, with a
      reduction in cell size, increased mitochondrial content, enhanced O2 consumption,
      increased transcription of adiponectin and of brown adipose tissue (BAT) genes. A
      single dose of oral ABA (1MUg/kg body weight) increased BAT glucose uptake 2-fold
      in treated rats compared with untreated controls. One-month-long ABA treatment at
      the same daily dose significantly upregulated expression of BAT markers in the
      WAT and in WAT-derived preadipocytes from treated mice compared with untreated
      controls. These results indicate a hitherto unknown role of LANCL2 in adipocyte
      sensitivity to insulin-stimulated glucose uptake and suggest a role for ABA in
      the induction and maintenance of BAT activity.

PMID- 27871881
TI  - Targeting brain and peripheral plasticity of the lipidome in acute kainic acid
      induced epileptic seizures in mice via quantitative mass spectrometry.
AB  - Epilepsy is a highly common chronic neurological disorder, manifested in many
      different types, affecting ~1% of the worldwide human population. The molecular
      mechanisms of epileptogenesis have not yet been clarified, and pharmacoresistance
      exhibited by 30-40% of epilepsy patients remains a major obstacle in medical
      care. Growing evidence indicates a role of lipid signalling pathways in
      epileptogenesis, thus lipid signals emerge as potential biomarkers for the onset
      and evolving course of the epileptic disorder, as well as potential therapeutic
      agents and targets. For this purpose, we applied a lipidomic strategy to unravel
      lipid alterations in brain regions, periphery tissues and plasma that are
      specific for acute epileptic seizures in mice at 1h after seizure induction by
      systemic kainic acid injection as compared to vehicle controls. Specifically,
      levels of (i) selected phospholipids and sphingomyelins, (ii) the
      endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), and the
      endocannabinoid-related compounds oleoylethanolamide (OEA) and
      palmitoylethanolamide (PEA), (iii) arachidonic acid (AA), (iv) selected
      eicosanoids, and (v) fatty acyl content of lipidome were determined in pulverized
      tissues from six brain regions of kainic acid induced epileptic seizure models
      and vehicle controls: hypothalamus, hippocampus, thalamus, striatum, cerebellum
      and cerebral cortex, and from peripheral organs, such as heart and lungs, and in
      plasma. Alterations in lipid levels after acute epileptic seizures as compared to
      non-seizure controls were found to be brain region- and periphery tissue
      specific, including specific plasma lipid correlates, highlighting their value as
      marker candidates in translational research studies, and/or drug discovery and
      response monitoring.

PMID- 27871882
TI  - Schistosomal-derived lysophosphatidylcholine triggers M2 polarization of
      macrophages through PPARgamma dependent mechanisms.
AB  - Mansonic schistosomiasis is a disease caused by the trematode Schistosoma
      mansoni, endemic to tropical countries. S. mansoni infection induces the
      formation of granulomas and potent polarization of Th2-type immune response.
      There is great interest in understanding the mechanisms used by this parasite
      that causes a modulation of the immune system. Recent studies from our group
      demonstrated that lipids of S. mansoni, including lysophosphatidylcholine (LPC)
      have immunomodulatory activity. In the present study, our aim was to investigate
      the role of lipids derived from S. mansoni in the activation and polarization of
      macrophages and to characterize the mechanisms involved in this process.
      Peritoneal macrophages obtained from wild type C57BL/6mice or bone marrow derived
      macrophages were stimulated in vitro with lipids extracted from adult worms of S.
      mansoni. We demonstrated that total schistosomal-derived lipids as well as
      purified LPC induced alternatively activated macrophages/M2 profile observed by
      increased expression of arginase-1, mannose receptor, Chi3l3, TGFbeta and
      production of IL-10 and PGE2 24h after stimulation. The involvement of the
      nuclear receptor PPARgamma in macrophage response against LPC was investigated.
      Through Western blot and immunofluorescence confocal microscopy we demonstrated
      that schistosomal-derived LPC induces increased expression of PPARgamma in
      macrophages. The LPC-induced increased expression of arginase-1 were
      significantly inhibited by the PPAR-gamma antagonist GW9662. Together, these
      results demonstrate an immunomodulatory role of schistosomal-derived LPC in
      activating macrophages to a profile of the type M2 through PPARgamma-dependent
      mechanisms, indicating a novel pathway for macrophage polarization triggered by
      parasite-derived LPC with potential implications to disease pathogenesis.

PMID- 27871883
TI  - Importance of phosphatidylcholine on the chloroplast surface.
AB  - In plant cells, phosphatidylcholine (PC) is a major glycerolipid of most
      membranes but practically lacking from the plastid internal membranes. In
      chloroplasts, PC is absent from the thylakoids and the inner envelope membrane.
      It is however the main component of the outer envelope membrane, where it
      exclusively distributes in the outer monolayer. This unique distribution is
      likely related with operational compartmentalization of plant lipid metabolism.
      In this review, we summarize the different mechanisms involved in homeostasis of
      PC in plant cells. The specific origin of chloroplast PC is examined and the
      involvement of the P4-ATPase family of phospholipid flippases (ALA) is considered
      with a special attention to the recently reported effect of the endoplasmic
      reticulum-localized ALA10 on modification of chloroplast PC desaturation. The
      different possible roles of chloroplast PC are then discussed and analyzed in
      consideration of plant physiology.

PMID- 27871884
TI  - Structural characterization of recombinant human fibroblast growth factor
      receptor 2b kinase domain upon interaction with omega fatty acids.
AB  - The mutated recombinant kinase domain of human fibroblast growth factor receptor
      2b (hFGFR2b) is overexpressed and purified, and its structural changes upon the
      interaction with three unsaturated fatty acids (UFAs), oleic, linoleic and alpha
      linolenic are studied. This interaction is investigated to find out about the
      folding and unfolding effect of unsaturated fatty acids on the kinase domain
      structure of hFGFR2b. Recombinant pLEICS-01 vectors, containing the mutated
      coding region of hFGFR2b, are expressed in the standard Escherichia coli BL21
      (DE3) host cells and purified by Ni2+-NTA affinity chromatography. While
      polyacrylamide gel electrophoresis characterizes the functionality of recombinant
      protein, its structural changes are studied in the presence and absence of
      various concentrations of oleic, alpha-linolenic and linoleic acids using
      circular dichroism (CD) and fluorescence spectroscopy. Far ultraviolet CD results
      show that unsaturated fatty acids do not change the secondary structure of the
      recombinant kinase domain of hFGFR2b. However, chemical denaturation analysis
      confirms that all three UFAs destabilize the tertiary structure of recombinant
      protein. A decrease in the fluorescence intensity without any significant red or
      blue shift (336+/-1nm) reflects a variation in the tertiary structure of protein.
      The direct interaction of the studied UFAs with hFGFR2b reduces the
      conformational stability of their kinase domains. The structural changes in
      hFGFR2b in the presence of UFAs may be necessary for hFGFR2b to adjust the signal
      transduction and regulate the key cellular processes.

PMID- 27871885
TI  - Vestibular signals of self-motion modulate global motion perception.
AB  - Certain visual stimuli can have two possible interpretations. These perceptual
      interpretations may alternate stochastically, a phenomenon known as bistability.
      Some classes of bistable stimuli, including binocular rivalry, are sensitive to
      bias from input through other modalities, such as sound and touch. Here, we
      address the question whether bistable visual motion stimuli, known as plaids, are
      affected by vestibular input that is caused by self-motion. In Experiment 1, we
      show that a vestibular self-motion signal biases the interpretation of the
      bistable plaid, increasing or decreasing the likelihood of the plaid being
      perceived as globally coherent or transparently sliding depending on the
      relationship between self-motion and global visual motion directions. In
      Experiment 2, we find that when the vestibular direction is orthogonal to the
      visual direction, the vestibular self-motion signal also biases the direction of
      one-dimensional motion. This interaction suggests that the effect in Experiment 1
      is due to the self-motion vector adding to the visual motion vectors. Together,
      this demonstrates that the perception of visual motion direction can be
      systematically affected by concurrent but uninformative and task-irrelevant
      vestibular input caused by self-motion.

PMID- 27871886
TI  - Tetrahalogenated benzimidazole D-ribonucleosides are active against rat
      cytomegalovirus.
AB  - BACKGROUND: Benzimidazole D-ribonucleosides are potent and selective inhibitors
      of CMV infection that have been shown to target the viral terminase, the enzyme
      complex responsible for viral DNA cleavage into single unit-length genomes and
      subsequent DNA packaging into procapsids. Here, we evaluated the viral inhibition
      by benzimidazole D-ribonucleosides against rat cytomegalovirus (RCMV). METHODS:
      Antiviral activity of compounds Cl4RB and BTCRB against RCMV was quantified by
      measurement of plaque formation. Yield assays and electron microscopy of thin
      sections was performed using RCMV-infected cells in the presence or absence of
      the compounds. The effects of Cl4RB and BTCRB on cleavage of concatemers was
      analyzed by pulsed-field gel electrophoresis. To characterize the behaviour of
      the antiviral compounds in a more physiological environment, a 3D cell culture
      model was employed where cells are embedded in an extracellular matrix using rat
      tail collagen I. RESULTS: Both compounds had an inhibitory effect against RCMV-E.
      Electron microscopy revealed that only few virions were formed in RCMV-E infected
      cells in the presence of the compounds. Pulsed-field gel electrophoresis showed
      that DNA concatemers failed to be processed in the presence of the compounds.
      Yield Assays showed a comparable viral growth in the 3D vs. 2D cell culture as
      well as inhibition in the presence of Cl4RB or BTCRB for RCMV-E/GFP. CONCLUSIONS:
      These results demonstrate that the tetrahalogenated benzimidazole D
      ribonucleosides are effective against RCMV-E by preventing cleavage of
      concatemeric DNA and nuclear egress of mature capsids.

PMID- 27871887
TI  - A silk peptide fraction restores cognitive function in AF64A-induced Alzheimer
      disease model rats by increasing expression of choline acetyltransferase gene.
AB  - This study investigated the effects of a silk peptide fraction obtained by
      incubating silk proteins with Protease N and Neutrase (SP-NN) on cognitive
      dysfunction of Alzheimer disease model rats. In order to elucidate underlying
      mechanisms, the effect of SP-NN on the expression of choline acetyltransferase
      (ChAT) mRNA was assessed in F3.ChAT neural stem cells and Neuro2a neuroblastoma
      cells; active amino acid sequence was identified using HPLC-MS. The expression of
      ChAT mRNA in F3.ChAT cells increased by 3.79-fold of the control level by
      treatment with SP-NN fraction. The active peptide in SP-NN was identified as
      tyrosine-glycine with 238.1 of molecular weight. Male rats were orally
      administered with SP-NN (50 or 300mg/kg) and challenged with a cholinotoxin
      AF64A. As a result of brain injury and decreased brain acetylcholine level, AF64A
      induced astrocytic activation, resulting in impairment of learning and memory
      function. Treatment with SP-NN exerted recovering activities on acetylcholine
      depletion and brain injury, as well as cognitive deficit induced by AF64A. The
      results indicate that, in addition to a neuroprotective activity, the SP-NN
      preparation restores cognitive function of Alzheimer disease model rats by
      increasing the release of acetylcholine.

PMID- 27871889
TI  - Spontaneous prosocial choice by captive bottlenose dolphins, Tursiops truncatus.
AB  - Dolphins exhibit prosocial behavior across several different contexts. However,
      only a few experimental studies have investigated the psychological mechanisms
      underlying this behavior. In this study, we investigated the mechanisms
      underlying prosociality in bottlenose dolphins (Tursiops truncatus). In the
      experiments, water shower devices, developed as environmental enrichment items,
      were used. Two paradigms were used to measure prosociality. The first was the
      prosocial choice task, involving the subject typically being offered one choice
      between two options. The first option provided a reward (take a shower) to both
      the subject and partner (prosocial choice). The second option provided a reward
      only to the subject (selfish choice). The second paradigm was the giving
      assistance task, involving the subject being provided a choice between providing
      instrumental help to the partner (prosocial choice) or doing nothing. It was
      observed that the subjects chose the prosocial choices in both paradigms. In
      these experiments, prosocial choices were spontaneously taken without requests
      from the partners. These results indicated that the dolphins show preference for
      other-regarding behavior.

PMID- 27871888
TI  - Multidrug and toxin extrusion proteins mediate cellular transport of cadmium.
AB  - Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to
      human health worldwide. As compared to the extensive research in Cd tissue
      accumulation, little was known about the elimination of Cd, particularly its
      toxic form, Cd ion (Cd2+). In this study, we aimed to examine whether Cd2+ is a
      substrate of multidrug and toxin extrusion proteins (MATEs) that are important in
      renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK
      hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to
      study the cellular transport and toxicity of Cd2+. The cells overexpressing MATEs
      showed a 2-4 fold increase of Cd2+ uptake that could be blocked by the MATE
      inhibitor cimetidine. A saturable transport profile was observed with the
      Michaelis-Menten constant (Km) of 130+/-15.8MUM for HEK-hMATE1; 139+/-21.3MUM for
      HEK-hMATE2-K; and 88.7+/-13.5MUM for HEK-mMate1, respectively. Cd2+ could inhibit
      the uptake of metformin, a substrate of MATE transporters, with the half maximal
      inhibitory concentration (IC50) of 97.5+/-6.0MUM, 20.2+/-2.6MUM, and 49.9+/
      6.9MUM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In
      addition, hMATE1 could transport preloaded Cd2+ out of the HEK-hMATE1 cells, thus
      resulting in a significant decrease of Cd2+-induced cytotoxicity. The present
      study has provided the first evidence supporting that MATEs transport Cd2+ and
      may function as cellular elimination machinery in Cd intoxication.

PMID- 27871890
TI  - Respiratory dynamics in phonation and breathing-A real-time MRI study.
AB  - The respiratory system is a central part of voice production, but for phonation
      neither the underlying functional relations between diaphragm (DPH) and rib cage
      (RC), nor differences to normal breathing are yet understood. This study aims to
      compare respiratory dynamics in phonation and breathing via dynamic MRI of the
      lung. Images of the breathing apparatus of 6 professional singers were captured
      in a 1.5T MRI system in supine position during vital capacity breathing and
      maximal long sustained phonation at 3 different pitches and loudness conditions.
      In a dynamic series of cross-sectional images of the lung, distances between
      characteristic anatomical landmarks were measured. During exhalation in normal
      breathing the diaphragm and rib cage moved synchronously to reduce lung volume,
      but during phonation different functional units could be identified, which
      support phonation by facilitating the control of subglottic pressure.

PMID- 27871891
TI  - Long-term alcohol exposure elicits hippocampal nonsynaptic epileptiform activity
      changes associated with expression and functional changes in NKCC1, KCC2 co
      transporters and Na+/K+-ATPase.
AB  - Nonsynaptic mechanism changes, particularly the enhancement of NKCC1 expression
      in the dentate gyrus (DG) after 4weeks of ethanol consumption, motivate the
      present work, in which rats were submitted to a period of chronic consumption
      (12weeks). Four groups of six animals (6-week-old male Wistar rats) were formed,
      including the control (C), ethanol 1 (E1), ethanol 2 (E2) and ethanol 3 (E3)
      groups. The rats in the E1, E2 and E3 groups were treated daily with a 30% v/v
      solution of ethanol, administered via oral gavage (1.0, 2.0 and 3.0g/kg,
      respectively). Nonsynaptic epileptiform activities (NEA) were induced by means of
      the zero-Ca2+ and high-K+ model using hippocampal slices and were recorded in the
      DG. The presence of NKCC1, KCC2, alpha1-Na+/K+-ATPase and GFAP immunoreactivity
      was analyzed. The results demonstrate that alcohol consumption changes NEA, and
      these changes are more prominent at the lower dosage. An increase in the DC
      shifts associated with epileptiform discharges was present with the low dose.
      This increase was correlated with the increment of NKCC1 expression. Confocal
      microscopy images indicate the NKCC1 increase was pronounced in the initial
      axonal segment of granule cells. The blockage of these cotransporters during NEA
      induction with bumetanide suppressed the DC shift increase and diminished all
      parameters of NEA that were quantified for all groups treated with ethanol.
      Therefore, the increase in NKCC1 expression and the effective activity of this
      cotransporter, which were observed in the treated groups, suggest that drugs that
      act for block NKCC1 represent promising strategies for diminishing the effects of
      alcohol damage on the brain.

PMID- 27871892
TI  - Pso p27, a SERPINB3/B4-derived protein, is most likely a common autoantigen in
      chronic inflammatory diseases.
AB  - Autoimmune diseases are characterized by chronic inflammatory reactions localized
      to an organ or organ-system. They are caused by loss of immunologic tolerance
      toward self-antigens, causing formation of autoantibodies that mistakenly attack
      their own body. Psoriasis is a chronic inflammatory autoimmune skin disease in
      which the underlying molecular mechanisms remain elusive. In this review, we
      present evidence accumulated through more than three decades that the serpin
      derived protein Pso p27 is an autoantigen in psoriasis and probably also in other
      chronic inflammatory diseases. Pso p27 is derived from the serpin molecules
      SERPINB3 and SERPINB4 through non-canonical cleavage by mast cell chymase. In
      psoriasis, it is exclusively found in skin lesions and not in uninvolved skin.
      The serpins are cleaved into three fragments that remain associated as a Pso p27
      complex with novel immunogenic properties and increased tendency to form large
      aggregates compared to native SERPINB3/B4. The amount of Pso p27 is directly
      correlated to disease activity, and through formation of complement activating
      immune-complexes, Pso p27 contribute to the inflammation in the skin lesions.
      SERPINB3/B4 are expressed in skin fibroblasts and keratinocytes, but normally
      absent in mast cells. Overexpression of the serpins may be induced by
      inflammation and hypoxia, resulting in mast cell uptake via yet unknown
      mechanisms. Here the generation and subsequent release of Pso p27 aggregates may
      promote an inflammatory loop that contributes to the chronicity of psoriasis and
      other autoimmune diseases.

PMID- 27871894
TI  - Optimizing gDNA extraction from fresh frozen meningioma tissue for downstream
      genetic analysis.
AB  - OBJECTIVE: Meningioma is the most common brain tumor. Genetic mutations in
      meningioma that include deletion of the neurofibromatosis type 2 gene, (NF2),
      offer diagnostic information on tumor behavior, recurrence and potential response
      to treatment. Obtaining high-grade genetic material is critical for accurate,
      sensitive and robust molecular testing. Currently, no standardized procedure
      exists for extracting gDNA from meningioma, and this problem was addressed in
      this report. METHOD: This study compared the yield and quality of extracted gDNA
      from patient meningioma specimens using an optimized phenol chloroform method and
      two commercial silica column-based extractions kits and tested respective
      performances as template in qPCR tests and multiplex ligation-dependent probe
      amplification (MLPA) NF2 screening. RESULTS: Mean gDNA yields were comparable for
      each method tested; however, phenol chloroform extraction outperformed column
      based kits in all other quality assurance metrics examined. Phenol chloroform
      extracted gDNA was highly pure, and of a higher fragment size species when
      compared to column prepared gDNA. qPCR of GAPDH, B2MG, and RPL37A housekeeping
      genes demonstrated variance in cycle thresholds between patient samples was much
      lower in the phenol chloroform group. Similarly, primer efficiencies were
      significantly improved in this sample group which translated to a broader qPCR
      linear dynamic range and much improved qPCR performance at low concentrations of
      template. MLPA screening identified NF2 gene deletions in 6 of 12 meningioma
      samples. Inconsistencies in copy number data for NF2 and reference regions of the
      genome were observed between gDNA sample extraction groups that included both
      false negative and positive errors in silica column derived gDNA samples.
      CONCLUSIONS: This study outlines a highly robust phenol chloroform extraction
      method for obtaining high-quality gDNA from frozen meningioma tissue and
      highlights the significance of performing adequate quality assurance when using
      gDNA for downstream genetic analysis. Most importantly, we demonstrate using gDNA
      extracted with silica column based kits can lead to diagnostic errors when
      screening NF2 deletions in meningiomas with MLPA.

PMID- 27871893
TI  - Clinical effects of pre-transplant serum 25-hydroxyvitamin D level on post
      transplant immunologic and non-immunologic outcomes in kidney transplant
      recipients.
AB  - BACKGROUND: The aim of this study was to investigate the effects of pre
      transplant serum 25-hydroxyvitamin D (25(OH)D) level on non-immunologic and
      immunologic aspects of post-transplant clinical outcomes in kidney transplant
      recipients (KTRs). METHODS: We investigated 174 KTRs with low immunologic risk at
      baseline. We divided the patients into three groups according to baseline serum
      25(OH)D level and compared the post-transplant clinical outcomes of acute
      rejection, infectious complications, and osteoporosis among the groups. RESULT:
      Thirty cases of biopsy-proven acute rejection (BPAR) were detected during the
      first year after KT. In the highest tertile, the rate of acute rejection (8.6%)
      was significantly lower than that in the lowest tertile (25.4%) (p=0.016), and a
      high 25(OH)D level was independently associated with a low incidence of BPAR in
      multivariate analysis. In contrast, serum 25(OH)D level did not show a
      significant association with overall or any specific type of infectious
      complication. Lipid profile, intact parathyroid hormone (PTH) level, and
      hemoglobin level were similar among the three tertile groups. The incidence of
      osteoporosis and bone mineral density (BMD) score were also similar across all
      three groups. CONCLUSIONS: Pre-transplant serum 25(OH)D level is a significant
      predictor of acute rejection, but it does not predict infection or metabolic
      complications.

PMID- 27871895
TI  - Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and
      dental fluorosis through oxidative stress-mediated Caspase pathways.
AB  - Fluoride is an environmental toxicant and induces dental fluorosis and oxidative
      stress. Lycopene (LYC) is an effective antioxidant that is reported to attenuate
      fluoride toxicity. To determine the effects of LYC on sodium fluoride (NaF) 
      induced teeth and ameloblasts toxicity, rats were treated with NaF (10 mg/kg)
      and/or LYC (10 mg/kg) by orally administration for 5 weeks; ameloblasts were
      treated with NaF (5 mM) and/or LYC (2 MUM) for 6 h. We found that the
      concentrations of fluoride, malondialdehyde (MDA) and reactive oxygen species
      (ROS), gene expressions and activities of Caspase-9 and Caspase-3, and the gene
      expressions of Bax were significantly decreased, while the activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GPX), the gene expression
      of Bcl-2 were significantly increased in the LYC + NaF-treated rats group;
      concentrations of MDA and ROS, gene expressions and activities of Caspase-9 and
      Caspase-3, and the gene expression of Bax, and ameloblasts apoptosis rate were
      significantly decreased, while the activities of SOD and GPX, the gene expression
      of Bcl-2 were significantly increased in the LYC + NaF-treated ameloblasts group.
      These results suggest that LYC significantly combated NaF-induced ameloblasts
      apoptosis and dental fluorosis by attenuation oxidative stress and down
      regulation Caspase pathway.

PMID- 27871896
TI  - Gastroprotective and ulcer healing effects of hydroethanolic extract of leaves of
      Caryocar coriaceum: Mechanisms involved in the gastroprotective activity.
AB  - This work aimed to determine the chemical fingerprint of hydroethanolic extract
      of leaves of Caryocar coriaceum (HELCC) and the gastroprotective activity. The
      chemical fingerprint of HELCC was analyzed by HPLC-DAD, to quantify total phenols
      and flavonoids were carried out by Folin-Ciocalteu reagent and aluminum chloride
      assay, while in vitro antioxidant activity was evaluated by the DPPH method. The
      methods used to determine pharmacological activity were: gastroprotective
      screening test in classical models of induced acute and chronic gastric lesions
      and physical barrier test. Further assays were performed to demonstrate the
      involvement of NO, prostaglandins, ATP-dependent potassium channels, TRPV,
      noradrenergic alpha2 receptors, histamines, and opioids. The DPPH method
      demonstrated the antioxidant activity of the extract, in vitro, explained by the
      presence of polyphenols and flavonoids. Oral administration of the extract,
      previously dissolved in deionized water, at a dose of 100 mg/kg decreased the
      lesions induced by indomethacin, acidified ethanol, ethanol and acetic acid by
      75.0, 72.8, 69.4 and 86.2% respectively. It was demonstrated that opioid
      receptors, alpha2-adrenergic receptors and primary afferent neurons sensitive to
      capsaicin were involved in the mechanism of gastric protection, in addition to
      the contribution of NO and prostaglandins. The results show that extract is a
      promising candidate for the treatment of gastric ulcers.

PMID- 27871897
TI  - Sauchinone exerts anticancer effects by targeting AMPK signaling in
      hepatocellular carcinoma cells.
AB  - Sauchinone is a pharmacologically active compound isolated from Saururus
      chinensis, which has been used as a traditional Oriental medicine to treat fever,
      jaundice, and various inflammatory diseases. In this study, we investigated the
      effect of sauchinone against hepatocellular carcinoma (HCC) and sought to
      elucidate the mechanism involved. Cell viability was measured by an MTT assay.
      Cell cycle distributions and the mitochondrial membrane potential were analyzed
      using flow cytometry. Cell death was analyzed by annexin V assay, 4',6-diamidino
      2-phenylindole staining, and terminal deoxynucleotidyl transferase dUTP nick-end
      labeling assay. Protein and mRNA levels were assessed by western blot and real
      time PCR, respectively. Malignant properties were investigated by a wound healing
      migration assay and invasion assay. Sauchinone suppressed the proliferation of
      human HCC cells in a dose-dependent manner. Moreover, it induced the G0/G1 phase
      cell cycle arrest and mitochondrial dysfunction and then triggered the apoptosis
      by activating the JNK/p38 pathway in Huh-7 cells. In addition, sauchinone induced
      the activation of the AMP-activated protein kinase (AMPK) pathway, and compound C
      (an AMPK inhibitor) blocked the sauchinone-induced mitochondrial dysfunction. The
      AMPK activation by sauchinone inhibited the phosphorylation of the mammalian
      target of rapamycin (mTOR) and its downstream targets, such as ribosomal protein
      S6 kinase 1 and eIF4E-binding protein 1. Furthermore, sauchinone attenuated key
      proangiogenic factors, including hypoxia-inducible factor-1alpha, vascular
      endothelial growth factor, and plasminogen activator inhibitor-1, resulting in
      decreased migration and invasion of HCC cells. These results provide evidence for
      sauchinone to be considered as a potent anticancer agent by targeting of the AMPK
      mTOR pathway in HCC.

PMID- 27871899
TI  - Balkan Endemic Nephropathy - Still continuing enigma, risk assessment and
      underestimated hazard of joint mycotoxin exposure of animals or humans.
AB  - The spreading of mycotoxic nephropathy in animals/humans was studied. The
      possible etiological causes provoking this nephropathy were carefully reviewed
      and analyzed. The natural content of the most frequent nephrotoxic mycotoxins in
      target feedstuffs/foods were investigated, in addition to their significance for
      development of renal damages in endemic areas. An estimation of the level of
      exposure of humans to the nephrotoxic mycotoxin, ochratoxin A (OTA), is made. The
      possible synergism or additive effects between some target mycotoxins in the
      development of nephropathy is also covered. The significance of joint mycotoxin
      interaction and masked mycotoxins, in addition to some newly isolated fungal
      toxic agents in the complicated etiology of mycotoxic nephropathy ranged in
      Balkan countries is discussed. The importance of some target fungal species which
      can induce kidney damages was evaluated. The morphological/ultrastructural,
      functional and toxicological similarities between human and animal nephropathy
      are studied. The possible hazard of low content of combinations of some target
      mycotoxins in food or feedstuff ingested by pigs, chickens or humans under
      natural conditions is evaluated and a risk assessment was made. Some different
      but more effective manners of prophylaxis and/or prevention against OTA
      contamination of feedstuffs/foods are suggested. A survey was made in regard to
      the best possible ways of veterinary hygiene control of OTA-exposed animals at
      slaughter time for preventing the entrance of OTA in commercial feedstuffs/food
      channels with a view to reduce the possible health hazard for humans. The
      economic efficacy and applicability of such preventive measures is additionally
      discussed and some practical suggestions are made.

PMID- 27871898
TI  - The cannabinoid beta-caryophyllene (BCP) induces neuritogenesis in PC12 cells by
      a cannabinoid-receptor-independent mechanism.
AB  - Beta-caryophyllene (BCP) is a phytocannabinoid whose neuroprotective activity has
      been mainly associated with selective activation of cannabinoid-type-2 (CB2)
      receptors, inhibition of microglial activation and decrease of inflammation.
      Here, we addressed the potential of BCP to induce neuritogenesis in PC12 cells, a
      model system for primary neuronal cells that express trkA receptors, respond to
      NGF and do not express CB2 receptors. We demonstrated that BCP increases the
      survival and activates the NGF-specific receptor trkA in NGF-deprived PC12 cells,
      without increasing the expression of NGF itself. The neuritogenic effect of BCP
      in PC12 cells was abolished by k252a, an inhibitor of the NGF-specific receptor
      trkA. Accordingly, BCP did not induce neuritogenesis in SH-SY5Y neuroblastoma
      cells, a neuronal model that does not express trkA receptors and do not respond
      to NGF. Additionally, we demonstrated that BCP increases the expression of axonal
      plasticity-associated proteins (GAP-43, synapsin and synaptophysin) in PC12
      cells. It is known that these proteins are up-regulated by NGF in neurons and
      neuron-like cells, such as PC12 cells. Altogether, these findings suggest that
      BCP activates trka receptors and induces neuritogenesis by a mechanism
      independent of NGF or cannabinoid receptors. This is the first study to show such
      effects of BCP and their beneficial role in neurodegenerative processes should be
      further investigated.

PMID- 27871900
TI  - Insulin/adenosine axis linked signalling.
AB  - Regulation of blood flow depends on systemic and local release of vasoactive
      molecules such as insulin and adenosine. These molecules cause vasodilation by
      activation of plasma membrane receptors at the vascular endothelium. Adenosine
      activates at least four subtypes of adenosine receptors (A1AR, A2AAR, A2BAR,
      A3AR), of which A2AAR and A2BAR activation leads to increased cAMP level,
      generation of nitric oxide, and relaxation of the underlying smooth muscle cell
      layer. Vasodilation caused by adenosine also depends on plasma membrane
      hyperpolarization due to either activation of intermediate-conductance Ca2+
      activated K+ channels in vascular smooth muscle or activation of ATP-activated K+
      channels in the endothelium. Adenosine also causes vasoconstriction via a
      mechanism involving A1AR activation resulting in lower cAMP level and increased
      thromboxane release. Insulin has also a dual effect causing NO-dependent
      vasodilation, but also sympathetic activity- and increased endothelin 1 release
      dependent vasoconstriction. Interestingly, insulin effects require or are
      increased by activation or inactivation of adenosine receptors. This is
      phenomenon described for d-glucose and l-arginine transport where A2AAR and A2BAR
      play a major role. Other studies show that A1AR activation could reduce insulin
      release from pancreatic beta-cells. Whether adenosine modulation of insulin
      biological effect is a phenomenon that depends on co-localization of adenosine
      receptors and insulin receptors, and adenosine plasma membrane transporters is
      something still unclear. This review summarizes findings addressing potential
      involvement of adenosine receptors to modulate insulin effect via insulin
      receptors with emphasis in the human vasculature.

PMID- 27871901
TI  - The immunomodulation of a maternal translationally controlled tumor protein
      (TCTP) in Zhikong scallop Chlamys farreri.
AB  - Translationally controlled tumor protein (TCTP) is initially described as a
      highly conserved protein implicated in cell growth, and it is subsequently
      confirmed to play important roles in mediating the innate immune response,
      especially the inflammatory. In the present study, the full-length cDNA sequence
      of a TCTP from Zhikong scallop Chlamys farreri (designed as CfTCTP) was cloned by
      rapid amplification of cDNA ends (RACE) technique based on the expression
      sequence tag (EST) analysis. It was of 1230 bp with an open reading frame (ORF)
      of 543 bp encoding a polypeptide of 180 amino acids. The deduced amino acid
      sequence contained a conserved TCTP signature sequence (from I47 to E58) and it
      shared 26.1%-48.9% similarities with previously identified TCTPs. CfTCTP was
      clustered with the TCTP from Argopectehs irradias in the phylogenetic tree and
      was designated into a single branch of mollusk with TCTP from Ruditapes
      philippinarum. The mRNA transcripts of CfTCTP were constitutively expressed in
      all the tested tissues, including haemocytes, muscle, mantle, gill,
      hepatopancreas, kidney and gonad, with the highest expression level in
      hepatopancreas. The mRNA expression level of CfTCTP in oocytes and fertilized
      eggs kept at a higher level, and was down-regulated from 2-cell embryos to the
      lowest level in gastrula. Then it was up-regulated in trochophore and dropped
      down in the late veliger larvae to the similar level as that in oocytes. After
      pathogen-associated molecular patterns (PAMPs) stimulation, the expression of
      CfTCTP mRNA in haemocytes was increased at 3 or 6 h, and fall down to the normal
      level at 24 h. The recombinant protein of CfTCTP could induce the release of
      histamine from BT-549 cells. All these results indicated that CfTCTP was a pro
      inflammatory factor and it could be maternally transferred from female gonad to
      oocytes and offspring, and play pivotal role in the embryonic development and
      immune protection of scallops.

PMID- 27871903
TI  - Review of preclinical studies on pediatric general anesthesia-induced
      developmental neurotoxicity.
AB  - Thousands of infants and children undergo complicated surgical procedures that
      require prolonged periods of anesthesia and/or sedation each year. A growing body
      of preclinical research suggests pediatric anesthetics are harmful to the
      developing brain; yet, the extent to which these effects generalize to the
      clinical setting remains unclear. As there will be a continuing need for surgical
      and other interventions requiring sedation and/or anesthesia during the neonatal
      period, it seems clear that research efforts should focus on determining the
      extent to which general anesthetics can affect the developing brain as well as
      determining strategies for preventing or ameliorating the adverse effects
      associated with exposure to such agents. The purpose of this paper is to provide
      a review of the preclinical literature examining the effects of general
      anesthesia on brain and behavioral development. This paper will detail the
      effects of different anesthetic agents on various indices of neurotoxicity and
      functional outcomes as well as provide a review of potential protective compounds
      and suggestions for areas of future research.

PMID- 27871904
TI  - Steroidogenic effect of Erxian decoction for relieving menopause via the p
      Akt/PKB pathway in vitro and in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Erxian decoction (EXD), an empirical Chinese
      medicine formula, is effectively used in the clinical treatment of menopause
      related symptoms in China. Previous data from our group show that EXD has
      steroidogenic effect on natural menopausal Sprague-Dawley-rats (SD-rats) as an
      animal model of menopause. However, the mechanistic studies on steroidogenic
      effects of EXD are still inadequate. Hence, the mechanisms of steroidogenic
      effects of EXD were studied in vitro and in vivo in this study. MATERIALS AND
      METHODS: Menopause causes a decline of endocrine function and a series of
      symptoms. In this study, 16-20-month-old female SD rats with a low serum
      estradiol level were employed. Their endocrine functions after treatment with EXD
      (4.1g/kg) were assessed by determination of their serum estradiol level. Proteins
      involved in the steroidogenic pathway including StAR, 17betaHSD, 3betaHSD,
      aromatase, and activation of phosphorylated Protein Kinase B (p-Akt/PKB), as well
      as estradiol receptor proteins (ERalpha & ERbeta) after EXD treatment were
      analyzed. Kinase inhibition assay was conducted to confirm the mechanism of
      steroidogenic effects of EXD in vitro. MCF-7 and BT-483 cells were used to
      investigate whether EXD stimulated breast cancer cell proliferation. RESULTS:
      Results revealed a significantly ameliorated serum estradiol level, and a
      significantly increased expression of ovarian aromatase and PKB in the EXD
      treated rats. EXD attenuated 17beta-estradiol stimulated proliferation of breast
      cancer cells. CONCLUSIONS: The results obtained from immunoblotting and
      measurements of serum estradiol level of the present investigation revealed that
      EXD may relieve the menopausal syndrome through an upregulation of ovarian
      aromatase and p-PKB expression without stimulating the growth of breast cancer
      cells.

PMID- 27871905
TI  - The behavioural and neuroprotective outcomes when 670nm and 810nm near infrared
      light are applied together in MPTP-treated mice.
AB  - We have shown previously that when applied separately, 670nm and 810nm near
      infrared light (NIr) reduces behavioural deficits and offers neuroprotection in a
      MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's
      disease. Here, we explored the beneficial outcomes when these NIr wavelengths
      were applied both together, either concurrently (at the same time) or
      sequentially (one after the other). Mice received MPTP injections (total of
      50mg/kg) and had extracranial application of 670nm and/or 810nm NIr. Behavioural
      activity was tested with an open-field test and brains were processed for
      tyrosine hydroxylase immunohistochemistry and stereology. Our results showed that
      when 670nm and 810nm NIr were applied both together and sequentially, there was a
      greater overall beneficial outcome - increased locomotor activity and number of
      tyrosine hydroxylase immunoreactive cells in the substantia nigra pars compacta -
      than when they were applied either separately, or in particular, both together
      and concurrently. In summary, our findings have important implications for future
      use of NIr therapy in humans, that there are some combinations of wavelengths
      that provide more beneficial outcome than others.

PMID- 27871902
TI  - The effects of long-term estradiol treatment on social behavior and gene
      expression in adult female rats.
AB  - This study tested the effects of long-term estradiol (E2) replacement on social
      behavior and gene expression in brain nuclei involved in the regulation of these
      social behaviors in adult female rats. We developed an ultrasonic vocalization
      (USV) test and a sociability test to examine communications, social interactions,
      and social preference, using young adult female cagemates. All rats were
      ovariectomized (OVX) and implanted with a Silastic capsule containing E2 or
      vehicle, and housed in same-treatment pairs for a 3-month period. Then, rats were
      behaviorally tested, euthanized, and 5 nuclei in the brain's social decision
      making circuit were selected for neuromolecular profiling by a multiplex qPCR
      method. Our novel USV test proved to be a robust tool to measure numbers and
      types of calls emitted by cagemates that had been reintroduced after a 1-week
      separation. Results also showed that E2-treated OVX rats had profoundly decreased
      numbers of USV calls compared to vehicle-treated OVX rats. In a test of
      sociability, in which a female was allowed to choose between her cagemate or a
      same-treatment novel rat, we found few effects of E2 compared to vehicle,
      although interestingly, rats chose the cagemate over an unfamiliar conspecific.
      Gene expression results revealed that the supraoptic nucleus had the greatest
      number of gene changes caused by E2: Oxt, Oxtr and Avp were increased, and Drd2,
      Htr1a, Grin2b, and Gabbr1 were decreased, by E2. No genes were affected in the
      prefrontal cortex, and 1-4 genes were changed in paraventricular nucleus (Pgr),
      bed nucleus of the stria terminalis (Oxtr, Esr2, Dnmt3a), and medial amygdala
      (Oxtr, Ar, Foxp1, Tac3). Thus, E2 changes communicative interactions between
      adult female rats, together with selected expression of genes in the brain,
      especially in the supraoptic nucleus.

PMID- 27871906
TI  - Adenosine, but not guanosine, protects vaginal epithelial cells from Trichomonas
      vaginalis cytotoxicity.
AB  - Trichomonas vaginalis causes the most common non-viral sexually transmitted
      disease worldwide. The cytoadherence and cytotoxicity upon the vaginal epithelial
      cells are crucial for the infection. Extracellular nucleotides are released
      during cell damage and, along with their nucleosides, can activate purinoceptors.
      The opposing effects of nucleotides versus nucleosides are regulated by
      ectonucleotidases. Herein we evaluated the hemolysis and cytolysis induced by T.
      vaginalis, as well as the extracellular nucleotide hydrolysis along with the
      effects mediated by nucleotides and nucleosides on cytotoxicity. In addition, the
      gene expression of purinoceptors in host cells was determined. The hemolysis and
      cytolysis exerted by all T. vaginalis isolates presented positive Pearson
      correlation. All T. vaginalis isolates were able to hydrolyze nucleotides,
      showing higher NTPDase than ecto-5'-nucleotidase activity. The most cytotoxic
      isolate, TV-LACM6, hydrolyzes ATP, GTP with more efficiency than AMP and GMP. The
      vaginal epithelial cell line (HMVII) expressed the genes for all subtypes of P1,
      P2X and P2Y receptors. Finally, when nucleotides and nucleosides were tested, the
      cytotoxic effect elicited by TV-LACM6 was increased with nucleotides. In
      contrast, the cytotoxicity was reversed by adenosine in presence of EHNA, but not
      by guanosine, contributing to the understanding of the purinergic signaling role
      on T. vaginalis cytotoxicity.

PMID- 27871907
TI  - Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease.
AB  - Endothelial Nitric Oxide Synthase (eNOS) is crucial for vascular homeostasis.
      Polymorphisms T786C and G894T affect eNOS regulation and have been related to
      various diseases. Sickle Cell Disease (SCD), a clinically diverse chronic
      hemolytic anemia, implies impaired nitric oxide bioavailability. Our aim was to
      determine eNOS genotype for T786C and G894T polymorphisms in Greek patients with
      SCD and to elucidate its consequences and effects if any on clinical phenotype.
      Seventy nine steady state cases, mostly compound heterozygous for Sickle Cell
      anemia/beta thalassemia and 48 controls were measured. Peripheral blood DNA was
      extracted and genotyped with PCR-RFLPs and Sanger sequencing. Total RNA was
      extracted from 18 patients and 9 controls and eNOS mRNA levels were determined by
      real-time PCR. Genotypes, allele distribution and eNOS mRNA levels did not differ
      between patients and controls, or among patients with different beta globin gene
      mutations. The 786CC genotype was more common in S/S and beta0/S patients with
      retinopathy. Moreover, 894TT S/S and beta0/S patients tended to have a higher
      hematocrit than 894GG and GT ones. However, the T786C eNOS genotype does not seem
      to affect peripheral blood cell-derived eNOS mRNA levels, at least in steady
      state conditions. This work is the first one describing the effects of eNOS
      polymorphisms on different forms of SCD, the first enrolling SCD patients of
      Caucasian origin and the first determining eNOS mRNA levels in peripheral blood
      from steady-state SCD patients.

PMID- 27871908
TI  - Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane
      X (PXR) receptor.
AB  - The Pregnane X (PXR), Vitamin D (VDR) and Farnesoid X (FXR) nuclear receptors
      have been shown to be receptors of bile acids controlling their detoxification or
      synthesis. Chenodeoxycholic (CDCA) and lithocholic (LCA) acids are ligands of FXR
      and VDR, respectively, whereas 3-keto and acetylated derivates of LCA have been
      described as ligands for all three receptors. In this study, we hypothesized that
      oxidation or acetylation at position 3, 7 and 12 of bile acids DCA (deoxycholic
      acid), LCA, CA (cholic acid), and CDCA by detoxification enzymes or microbiome
      may have an effect on the interactions with bile acid nuclear receptors. We
      employed reporter gene assays in HepG2 cells, the TR-FRET assay with recombinant
      PXR and RT-PCR to study the effects of acetylated and keto bile acids on the
      nuclear receptors activation and their target gene expression in differentiated
      hepatic HepaRG cells. We demonstrate that the DCA 3,12-diacetate and CA 3,7,12
      triacetate derivatives are ligands of PXR and DCA 3,12-diacetate induces PXR
      target genes such as CYP3A4, CYP2B6 and ABCB1/MDR1. In conclusion, we found that
      acetylated DCA and CA are potent ligands of PXR. Whether the acetylated bile acid
      derivatives are novel endogenous ligands of PXR with detoxification or
      physiological functions should be further studied in ongoing experiments.

PMID- 27871909
TI  - Histone deacetylase inhibition enhances in-vivo bone regeneration induced by
      human periodontal ligament cells.
AB  - : Periodontal ligament cells have the potential to differentiate into bone
      forming osteoblasts and thus represent a good cellular candidate for bone
      regeneration. This study aimed to investigate the effect of inhibition of histone
      deacetylases, using the inhibitor Trichostatin A (TSA), on bone regeneration by
      human periodontal ligament cells (hPDLCs) in a mouse calvaria bone defect.
      METHODS: RUNX2 protein and its acetylation was analyzed by immunoprecipitation
      and western blotting. The effect of TSA on osteogenic differentiation of hPDLCs
      was investigated using in vitro 3D cultures. hPDLCs were pre-incubated with and
      without TSA and implanted in mouse calvaria defects with
      polycaprolactone/polyethylene glycol (PCL/PEG) co-polymer scaffold. Micro-CT
      scanning and bone histomorphometric analysis were used to quantify the amount of
      bone. Survival of hPDLCs as xenogenic grafts was verified by immunohistochemistry
      with anti-human beta1-integrin. The immunological response of mice against hPDLCs
      xenografts was evaluated by measuring total IgG and hPDLCs-specific IgG. RESULTS:
      Beside affecting histone protein, TSA also induced hyper-acetylation of RUNX2
      which might be a crucial mechanism for enhancing osteogenesis by hPDLCs. TSA
      enhanced mineral deposition by hPDLCs in in vitro 3D cultures and had no effect
      on cell viability. In vivo bone regeneration of mouse calvaria defects was
      significantly enhanced by TSA pre-treated hPDLCs. By using anti-human beta1
      integrin hPDLCs were shown to differentiate into osteocyte-like cells that were
      present in newly formed bone. hPDLCs, as a xenograft, slightly but not
      significantly induced an immunological response in recipient mice as demonstrated
      by the level of total IgG and hPDLCs-specific IgG. CONCLUSION: Inhibition of
      histone deacetylases by TSA enhanced in vivo bone regeneration by hPDLCs. The
      data strongly suggest a novel approach to regenerate bone tissue.

PMID- 27871911
TI  - In vitro and in vivo anti-inflammatory effects of theaflavin-3,3'-digallate on
      lipopolysaccharide-induced inflammation.
AB  - Inflammation is a defensive response against various harmful stimuli and stress
      conditions, such as tissue injury and one of the most common pathological
      processes occurring in human diseases. Theaflavin-3,3'-digallate, one of the
      theaflavins present in black tea, exhibits several bioactive properties,
      including the ability to lower the incidence of coronary heart disease, a
      positive effect on the bone mineral density, and the ability to prevent cancer.
      The aim of this study was to evaluate whether theaflavin-3,3'-digallate could
      reduce the production of pro-inflammatory cytokines in vivo and in vitro and
      ameliorate acute lung injury (ALI) in a mouse model. In this study, we
      demonstrated that theaflavin-3,3'-digallate suppressed the lipopolysaccharide
      (LPS)-induced phosphorylation of c-Jun N-terminal kinase and p38 mitogen
      activated protein kinase in RAW 264.7 macrophages. In addition, we also showed
      that theaflavin-3,3'-digallate inhibited the expression of tumor necrosis factor
      alpha, interleukin -1 beta, and interleukin 6 in phorbol myristate acetate 
      primed U937 and RAW 264.7 cells. Furthermore, theaflavin-3,3'-digallate treatment
      attenuated the severity of LPS-induced ALI in mice. These results suggested that
      theaflavin-3,3'-digallate might be a potential therapeutic candidate for the
      treatment of inflammation and inflammatory diseases.

PMID- 27871910
TI  - Pharmacological studies on the NOP and opioid receptor agonist PWT2-[Dmt1]N/OFQ(1
      13).
AB  - An innovative chemical strategy named peptide welding technology (PWT) has been
      developed for the facile synthesis of tetrabranched peptides. [Dmt1]N/OFQ(1-13)
      NH2 acts as a universal agonist for nociceptin/orphanin FQ (N/OFQ) and classical
      opioid receptors. The present study investigated the pharmacological profile of
      the PWT derivative of [Dmt1]N/OFQ(1-13)NH2 (PWT2-[Dmt1]) in several assays in
      vitro and in vivo after spinal administration in monkeys subjected to the tail
      withdrawal assay. PWT2-[Dmt1] mimicked the effects of [Dmt1]N/OFQ(1-13)-NH2
      displaying full agonist activity, similar affinity/potency and selectivity at
      human recombinant N/OFQ (NOP) and opioid receptors in receptor binding,
      stimulation of [35S]GTPgammaS binding, calcium mobilization in cells expressing
      chimeric G proteins, and BRET studies for measuring receptor/G-protein and
      receptor/beta-arrestin 2 interaction. In vivo in monkeys PWT2-[Dmt1] elicited
      dose-dependent and robust antinociceptive effects being more potent and longer
      lasting than [Dmt1]N/OFQ(1-13)-NH2. The analgesic action of PWT2-[Dmt1] was
      sensitive to the NOP receptor antagonist J-113397, but not naltrexone. Thus, the
      present study demonstrated that the tetrabranched derivative of [Dmt1]N/OFQ(1-13)
      NH2 obtained with the PWT technology maintains the in vitro pharmacological
      profile of the parent peptide but displays higher potency and longer lasting
      action in vivo.

PMID- 27871912
TI  - The modulation of delta responses in the interaction of brightness and emotion.
AB  - The modulation of delta oscillations (0.5-3.5Hz) by emotional stimuli is
      reported. Physical attributes such as color, brightness and spatial frequency of
      emotional visual stimuli have crucial effect on the perception of complex scene.
      Brightness is intimately related with emotional valence. Here we explored the
      effect of brightness on delta oscillatory responses upon presentation of
      pleasant, unpleasant and neutral pictures. We found that bright unpleasant
      pictures elicited lower amplitude of delta response than original unpleasant
      pictures. The electrophysiological finding of the study was in accordance with
      behavioral data. These results denoted the importance of delta responses on the
      examination of the association between perceptual and conceptual processes while
      in the question of brightness and emotion.

PMID- 27871914
TI  - Neonatal levels of adiponectin, interleukin-10 and interleukin-12 are associated
      with the risk of developing type 1 diabetes in childhood and adolescence: A
      nationwide Danish case-control study.
AB  - BACKGROUND/AIM: An in-depth understanding of the early phase of type 1 diabetes
      (T1D) pathogenesis is important for targeting primary prevention. We examined if
      14 preselected mediators of immune responses differed in neonates that later
      developed T1D compared to control neonates. METHODS: The study is a case-control
      study with a 1:2 matching. The individuals were born between 1981 through 2002.
      Cases were validated using the National Patient Register and the Danish Childhood
      Diabetes Register. Interleukin(IL)-1beta, IL-4, IL-6, IL-8, IL-10, IL-12p70,
      interferon gamma, tumor necrosis factor alpha, transforming growth factor beta 1
      (active form), leptin, adiponectin, c-reactive protein, mannose-binding lectin
      and soluble triggering receptor expressed on myeloid cells-1 were measured by
      using a flowmetric Luminex xMAP(r) technology. We tested two models both
      including a number of possible confounders. In the first model (model 1) we also
      adjusted for HLA-DQB1 genotype. A total of 1930 groups of assay-matched cases and
      controls (4746 individuals) were included in the statistical analyses. RESULTS:
      Adiponectin was negatively associated with later risk of T1D in both models
      (relative change (RC), model 1: 0.95, P=0.046 and model 2: 0.95, P=0.006). IL-10
      and IL-12 were both positively associated with T1D risk in the model 2 (RC, 1.19,
      P=0.006 and 1.07, P=0.02, respectively)-these results were borderline significant
      in model 1, but showed the same direction as the results from model 2.
      CONCLUSIONS: Our results indicate that specific immunological signatures are
      already present at time of birth in children developing T1D before the age of
      18years.

PMID- 27871913
TI  - What can time-frequency and phase coherence measures tell us about the genetic
      basis of P3 amplitude?
AB  - In a recent comprehensive investigation, we largely failed to identify
      significant genetic markers associated with P3 amplitude or to corroborate
      previous associations between P3 and specific single nucleotide polymorphisms
      (SNPs) or genes. In the present study we extended this line of investigation to
      examine time-frequency (TF) activity and intertrial phase coherence (ITPC) in the
      P3 time window, both of which are associated with P3 amplitude. Previous genome
      wide research has reported associations between P3-related theta and delta
      activity and individual genetic variants. A large, population-based sample of
      4211 subjects, comprising male and female adolescent twins and their parents, was
      genotyped for 527,828 single nucleotide polymorphisms (SNPs), from which over six
      million SNPs were accurately imputed. Heritability estimates were greater for TF
      energy than ITPC, whether based on biometric models or the combined influence of
      all measured SNPs (derived from genome-wide complex trait analysis). The
      magnitude of overlap in the specific SNPs associated with delta energy and ITPC
      and P3 amplitude was significant. A genome-wide analysis of all SNPs, accompanied
      by an analysis of approximately 17,600 genes, indicated a region of chromosome 2
      around TEKT4 that was significantly associated with theta ITPC. Analysis of
      candidate SNPs and genes previously reported to be associated with P3 or related
      phenotypes yielded one association surviving correction for multiple tests:
      between theta energy and CRHR1. However, we did not obtain significant
      associations for SNPs implicated in previous genome-wide studies of TF measures.
      Identifying specific genetic variants associated with P3 amplitude remains a
      challenge.

PMID- 27871915
TI  - Inhibition of siglec-1 by lentivirus mediated small interfering RNA attenuates
      atherogenesis in apoE-deficient mice.
AB  - BACKGROUND: Siglec-1 is highly expressed on circulating monocytes and plaque
      macrophages in atherosclerotic patients, but the exact role of Siglec-1 in
      atherosclerosis has not been elucidated. METHODS: Lentiviral vector containing
      small interfering RNA targeting Siglec-1 (Lv-shSiglec-1) or control vector (Lv
      shNC) were injected intravenously into 6-week old Apoe-/- mice. Then onset of
      atherosclerosis was observed. RESULTS: Siglec-1 was highly expressed in aortic
      plaques and it can be down-regulated by Lv-shSiglec-1 injection. The plaque area
      and serum pro-inflammatory cytokine (IL-1beta, IL-6, TNF-alpha and IL-17A) levels
      in Lv-shSiglec-1 mice were significantly lower than Lv-shNC mice, whereas IL-10
      was higher. Moreover, plaque macrophages accumulation in aortic wall in Lv
      shSiglec-1 mice was diminish, partly by decreased secretion of MCP-1/CXCL2 and
      CCR2/CXCR2 of aortas and monocytes, respectively. Furthermore, silencing of
      Siglec-1 can attenuate oxLDL uptake by peritoneal macrophages. CONCLUSIONS:
      Inhibition of Siglec-1 can prevent atherosclerotic lesion formation by suppress
      monocytes-endothelial cells adhesion and macrophages accumulation.

PMID- 27871917
TI  - Gonococcal Conjunctivitis: A Case Report of an Unusual Mode of Transmission.
AB  - BACKGROUND: Outside of the newborn period, development of gonococcal
      conjunctivitis is rare and predominantly occurs through autoinoculation. We
      report an unusual case of gonococcal conjunctivitis in a young woman exposed
      through direct inoculation. CASE: A 19-year-old woman presented with purulent
      ocular discharge, severe pain, and decreased vision unresponsive to topical
      antibiotics or ganciclovir approximately 3 weeks after accidental ocular exposure
      to seminal fluid during unprotected oral sex. Cultured ocular drainage grew
      Neisseria gonorrhea; vaginal and throat cultures were negative. She was
      successfully treated with ceftriaxone and doxycycline for 10 days. SUMMARY AND
      CONCLUSION: Clinicians should be aware of the potential for vision-threatening
      gonococcal conjunctivitis from exposure during sexual contact.

PMID- 27871916
TI  - Association of neurobehavioral performance with R2* in the caudate nucleus of
      asymptomatic welders.
AB  - OBJECTIVES: Welding fumes contain several metals including manganese (Mn) and
      iron (Fe) that may affect the nervous system. Previous studies of potential
      welding-related neurotoxicity have focused primarily on Mn exposure. The current
      study examined neurobehavioral and brain imaging changes in asymptomatic welders
      and their associations with both Mn and Fe exposure measurements. METHODS: Data
      were obtained from subjects with (n=46) and without (controls; n=31) a history of
      welding exposure. Occupational questionnaires estimated recent (HrsW; welding
      hours and E90; cumulative exposure, past 90days) and lifetime (YrsW; total
      welding years and ELT; cumulative exposure, lifetime) exposure. Brain MRI
      pallidal index (PI), R1 (1/T1), and R2* (1/T2*) were measured to estimate Mn and
      Fe concentrations in the basal ganglia [caudate nucleus (CN), putamen, and globus
      pallidus], amygdala, and hippocampus. Comprehensive neuropsychological tests were
      conducted to examine behavioral differences between welders and controls.
      Correlation analyses were conducted between neuropsychological tests and those
      exposure measurements that showed significant group differences. RESULTS:
      Compared to controls, welders had significantly higher R2* in the CN and lower
      performance on the Phonemic Fluency test. Correlation analyses revealed that
      welders' Phonemic Fluency scores were inversely associated with R2* in the CN,
      but not with the PI or R1 in any brain region of interest studied. DISCUSSION:
      The results showed that neurobehavioral performance for the asymptomatic welders
      in our study was worse than individuals who had not welded, and suggest the
      differences may be associated with higher Fe accumulation in the CN.

PMID- 27871918
TI  - The Effect of Interprofessional Student-Led Reproductive Health Education on
      Youths in Juvenile Detention.
AB  - STUDY OBJECTIVE: To assess the effects of an interprofessional student-led
      comprehensive sexual education curriculum in improving the reproductive health
      literacy among at-risk youths in detention. DESIGN, SETTING, AND PARTICIPANTS: We
      performed a prospective cohort study involving 134 incarcerated youth and an
      interprofessional team of 23 medical, nursing, and social work students, who
      participated in a comprehensive reproductive health curriculum over the course of
      3 days. INTERVENTIONS, AND MAIN OUTCOME MEASURES: Basic reproductive health
      knowledge, confidence in condom use with a new partner, and self-efficacy with
      regard to contraception use and sexual autonomy were assessed before and after
      completion of the curriculum. We also assessed the student teachers' level of
      comfort with teaching reproductive health to adolescents and their perception of
      interprofessionalism. RESULTS: Incarcerated youth showed a statistically
      significant increase in knowledge regarding sexually transmitted infections as
      well as self-reported confidence in condom use (P = .002). Self-efficacy in
      contraception use and sexual autonomy did not show significant improvement.
      Qualitative analysis of student teachers' surveys revealed theme categories
      regarding perception of youth, perception of self in teaching youth, perception
      of interacting with youth, and perception of working in interprofessional teams.
      CONCLUSIONS: Our program might represent a mutually beneficial community
      relationship to improve reproductive health literacy in this high-risk youth
      population.

PMID- 27871919
TI  - Motivational Interviewing to Promote Long-Acting Reversible Contraception in
      Postpartum Teenagers.
AB  - STUDY OBJECTIVE: To determine if teenage patients receiving prenatal care in an
      adolescent-focused clinic, emphasizing long-acting reversible contraception
      (LARC) using motivational interviewing techniques, had higher rates of uptake of
      postpartum LARC than a control group. DESIGN AND SETTING: Retrospective cohort
      study comparing young women who received prenatal care in an adolescent-focused
      setting with those enrolled in standard prenatal care. PARTICIPANTS: Adolescents
      between the ages of 13 and 17 years receiving prenatal care within the Maricopa
      Integrated Health safety-net system between 2007 and 2014. INTERVENTIONS:
      Motivational interviewing within the context of adolescent-focused prenatal care.
      MAIN OUTCOME MEASURES: Rates of uptake of LARC within 13 postpartum weeks.
      RESULTS: The adjusted rate of LARC for adolescent-focused prenatal care
      participants by 13 weeks postpartum was 38% (95% confidence interval [CI], 29%
      47%) compared with 18% (95% CI, 11%-28%) for standard care participants, with an
      adjusted odds ratio of LARC use of 2.8 (95% CI, 1.5-5.2). Among patients who
      received adolescent-focused prenatal care, most (27% vs 12.7%) were using an
      intrauterine device as opposed to an implantable contraceptive device.
      CONCLUSION: Participation in an adolescent-focused antepartum setting using
      motivational interviewing to emphasize postpartum LARC resulted in nearly 3 times
      higher rates of uptake compared with standard prenatal care.

PMID- 27871920
TI  - Integrating Long-Acting Reversible Contraception Services into New York City
      School-Based Health Centers: Quality Improvement to Ensure Provision of Youth
      Friendly Services.
AB  - STUDY OBJECTIVE, DESIGN, AND SETTING: Adolescents face barriers to accessing
      youth-friendly family planning services, specifically long-acting reversible
      contraception (LARC). School-based health centers (SBHCs) can provide youth
      friendly care. A quality improvement project was undertaken to assess quality of
      care before, during, and after LARC services at 3 SBHCs, and to identify specific
      strategies for improving these LARC services. PARTICIPANTS, INTERVENTIONS, AND
      MAIN OUTCOME MEASURES: We interviewed 18 female adolescents who received LARC
      services. Two independent reviewers coded deidentified verbatim transcripts;
      discrepancies were resolved by consensus with a third reviewer. A guide of themes
      was structured corresponding to Ambresin's domains of youth-friendly services.
      From these domains, we identified emerging themes using grounded theory, with a
      focus on practical suggestions for improving LARC services in SBHCs. RESULTS:
      Interviewees ranged in age from 15 to 19 (average: 17) years. Most had insertions
      (12 levonorgestrel intrauterine system (LNG-IUS); Mirena(r)), 1 copper
      intrauterine device (Paragard(r)), 5 contraceptive implant (Nexplanon(r)).
      Overall, participants were highly satisfied with SBHC LARC services. Within the
      domain of communication, 2 key themes emerged: balancing need for information
      with concerns about being overwhelmed by information; and interest in information
      that directly addresses misconceptions about LARCs. Suggested strategies included
      providing postprocedure "care packages" with information and supplies, and
      supporting a peer-based network of adolescent LARC users and previous patients to
      serve as a resource for new patients. CONCLUSION: This quality improvement
      project, conducted in a unique setting, gave adolescents a voice. The identified
      strategies for improving health education, social support, and outreach might be
      generalizable to other SBHCs. Future research could explore the effect of
      implementing these suggested strategies on reproductive health care use and
      outcomes at SBHCs.

PMID- 27871921
TI  - EEG frequency tagging using ultra-slow periodic heat stimulation of the skin
      reveals cortical activity specifically related to C fiber thermonociceptors.
AB  - The recording of event-related brain potentials triggered by a transient heat
      stimulus is used extensively to study nociception and diagnose lesions or
      dysfunctions of the nociceptive system in humans. However, these responses are
      related exclusively to the activation of a specific subclass of nociceptive
      afferents: quickly-adapting thermonociceptors. In fact, except if the activation
      of Adelta fibers is avoided or if A fibers are blocked, these responses
      specifically reflect activity triggered by the activation of Type 2 quickly
      adapting A fiber mechano-heat nociceptors (AMH-2). Here, we propose a novel
      method to isolate, in the human electroencephalogram (EEG), cortical activity
      related to the sustained periodic activation of heat-sensitive thermonociceptors,
      using very slow (0.2Hz) and long-lasting (75s) sinusoidal heat stimulation of the
      skin between baseline and 50 degrees C. In a first experiment, we show that when
      such long-lasting thermal stimuli are applied to the hand dorsum of healthy
      volunteers, the slow rises and decreases of skin temperature elicit a consistent
      periodic EEG response at 0.2Hz and its harmonics, as well as a periodic
      modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a
      second experiment, we demonstrate using an A fiber block that these EEG responses
      are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed
      approach constitutes a novel mean to study C fiber function in humans, and to
      explore the cortical processing of tonic heat pain in physiological and
      pathological conditions.

PMID- 27871922
TI  - Linking canonical microcircuits and neuronal activity: Dynamic causal modelling
      of laminar recordings.
AB  - Neural models describe brain activity at different scales, ranging from single
      cells to whole brain networks. Here, we attempt to reconcile models operating at
      the microscopic (compartmental) and mesoscopic (neural mass) scales to analyse
      data from microelectrode recordings of intralaminar neural activity. Although
      these two classes of models operate at different scales, it is relatively
      straightforward to create neural mass models of ensemble activity that are
      equipped with priors obtained after fitting data generated by detailed
      microscopic models. This provides generative (forward) models of measured
      neuronal responses that retain construct validity in relation to compartmental
      models. We illustrate our approach using cross spectral responses obtained from
      V1 during a visual perception paradigm that involved optogenetic manipulation of
      the basal forebrain. We find that the resulting neural mass model can distinguish
      between activity in distinct cortical layers - both with and without optogenetic
      activation - and that cholinergic input appears to enhance (disinhibit)
      superficial layer activity relative to deep layers. This is particularly
      interesting from the perspective of predictive coding, where neuromodulators are
      thought to boost prediction errors that ascend the cortical hierarchy.

PMID- 27871923
TI  - Omics analysis of mouse brain models of human diseases.
AB  - The identification of common gene/protein profiles related to brain alterations,
      if they exist, may indicate the convergence of the pathogenic mechanisms driving
      brain disorders. Six genetically engineered mouse lines modelling
      neurodegenerative diseases and neuropsychiatric disorders were considered. Omics
      approaches, including transcriptomic and proteomic methods, were used. The
      gene/protein lists were used for inter-disease comparisons and further functional
      and network investigations. When the inter-disease comparison was performed using
      the gene symbol identifiers, the number of genes/proteins involved in multiple
      diseases decreased rapidly. Thus, no genes/proteins were shared by all 6 mouse
      models. Only one gene/protein (Gfap) was shared among 4 disorders, providing
      strong evidence that a common molecular signature does not exist among brain
      diseases. The inter-disease comparison of functional processes showed the
      involvement of a few major biological processes indicating that brain diseases of
      diverse aetiologies might utilize common biological pathways in the nervous
      system, without necessarily involving similar molecules.

PMID- 27871924
TI  - MiR-335 regulates the chemo-radioresistance of small cell lung cancer cells by
      targeting PARP-1.
AB  - The role of miR-335 in the regulation of chemosensitivity and radiosensitivity of
      small cell lung cancer (SCLC) was investigated. miR-335 was significantly
      downregulated in multi-drug-resistant SCLC H69AR and H446DDP cells compared with
      parental cells as detected by qRT-PCR. Then, we demonstrated the negative
      correlation between miR-335 expression and the chemo-radiosensitivity of SCLC
      cells, including cell proliferation, cell clonality and cell apoptosis. In
      addition, miR-335 overexpression inhibited cell migration in vitro and tumor
      growth in vivo, whereas inhibition of miR-335 promoted cell migration and tumor
      growth. The underlying mechanism was further studied. Poly [ADP-ribose]
      polymerase 1 (PARP-1) was identified as a direct target gene of miR-335 in SCLC
      by bioinformatics analysis and validated via luciferase reporter assay.
      Overexpression of miR-335 decreased the expression of PARP-1 mRNA and protein,
      and NF-kappaB protein levels were correspondingly downregulated, thus regulating
      the chemo-radiosensitivity of SCLC. Taken together, these findings indicate that
      miR-335 may serve as a critical regulator of chemo-radiotherapy resistance in
      SCLC and a new potential therapeutic target.

PMID- 27871925
TI  - Identification and characterization of a phospholipid scramblase encoded by
      planarian Dugesia japonica.
AB  - Phospholipid scramblases (PLSCRs) are the conserved calcium-binding, type II
      transmembrane proteins synthesized in all eukaryotic organisms. In mammals, these
      proteins play essential roles in various physiological processes, especially in
      the immune responses. However, the existence of PLSCRs and their biological
      functions in planarian are still unknown at present. In this study, a new member
      of PLSCRs was identified in planarian Dugesia japonica (D. japonica), named
      DjPLSCR. The sequence analysis revealed that it contains an opening reading frame
      consisting of 726bp encoding a putative protein of 241 amino acids with a
      predicted molecular mass of ~28.7kDa and an isoelectric point of 6.21. Whole
      mount in situ hybridization showed that mRNAs of DjPLSCR are predominantly
      expressed in adult and regenerative pharynx which is an important organ of immune
      system in planarians. Importantly, we found that the transcription level of
      DjPLSCR was significantly upregulated when planarians were stimulated with the
      pathogen-associated molecular patterns [polyinosinic-polycytidylic acid,
      lipopolysaccharide, peptidoglycan and beta-glucan], suggesting that DjPLSCR is
      involved in the immune response upon pathogen invasion. Our findings provide the
      first experimental insights into the characteristics and potential functions of
      PLSCR in planarians.

PMID- 27871926
TI  - The telomere attrition rate is not accelerated in women born small for
      gestational age: A birth cohort study.
AB  - BACKGROUND: Physiologically, a reduction in telomere length (LTL) occurs with
      aging, but epigenetic changes may accelerate telomere shortening and also
      facilitate the onset of oxidative/inflammatory stress and the development of
      clinical/metabolic comorbidities in life spam. Although individuals born small
      for gestational age (SGA) may be related to those epigenetic changes, the
      assessment of LTL in individuals born SGA has yielded conflicting results (only
      cross-sectional studies) and has not been carried out in longitudinal studies. We
      performed a birth cohort study to evaluate the rate of telomere erosion in women
      born SGA in comparison to women born appropriate for gestational age (AGA)
      assessed at two different time points during the third decade of life. In our
      research, born SGA or AGA showed no difference in LTL shortening during a period
      of five years in the third decade of life. Our finding may have implications for
      understanding the natural history of diseases in lifespan because the same women
      (under the influence of similar environmental factors) may be accessed in
      different phases of life. Thus, the analysis of the present cohort population at
      a more advanced age may reveal a dynamics of telomere shortening different from
      here and its possible relation with onset of age-related diseases.

PMID- 27871927
TI  - Pulsed Magnetic Stimulation for Stress Urinary Incontinence: 1-Year Followup
      Results.
AB  - PURPOSE: Despite significant differences in success rates between surgical and
      nonsurgical treatments for female stress urinary incontinence, a few cross
      sectional surveys showed that most patients still prefer the latter. We evaluated
      the efficacy of the under studied nonsurgical treatment using pulsed magnetic
      stimulation for female stress urinary incontinence. MATERIALS AND METHODS: This
      randomized, double-blind, sham controlled study was performed in 120 female
      subjects at least 21 years old with stress urinary incontinence. Treatment
      involved pulsed magnetic stimulation for 2 sessions per week for 2 months (16
      sessions). After 2 months, subjects could opt for 16 additional sessions
      regardless of initial randomization. The primary response criterion was a 5-point
      reduction in the ICIQ-UI SF (International Consultation on Incontinence
      Questionnaire for Urinary Incontinence-Short Form) score. Key secondary response
      criteria included objective and subjective cure, supplemented by other secondary
      criteria. Followups were performed at months 1, 2, 5, 8 and 14. RESULTS: At 2
      months 45 of 60 subjects (75%) in the active arm vs 13 of 60 (21.7%) in the sham
      arm were treatment responders (p <0.001). After 2 months 24 subjects (40%) in the
      active arm and 41 (68%) in the sham arm elected additional active pulsed magnetic
      stimulation. At 14 months, subjects who received 32 sessions of active pulsed
      magnetic stimulation had the highest percentage of treatment responders (18 of 24
      or 75.0%), followed by those who received 16 sessions (26 of 36 or 72.2% and 28
      of 41 or 68.3%) and those who did not receive any active pulsed magnetic
      stimulation (4 of 19 or 21.1%) (p <0.001). CONCLUSIONS: The encouraging long-term
      response rates show that pulsed magnetic stimulation is an attractive nonsurgical
      alternative for patients who do not want to undergo surgery.

PMID- 27871928
TI  - The Effect of Dutasteride on Magnetic Resonance Imaging Defined Prostate Cancer:
      MAPPED-A Randomized, Placebo Controlled, Double-Blind Clinical Trial.
AB  - PURPOSE: Dutasteride, which is licensed for symptomatic benign prostatic
      hyperplasia, has been associated with a lower progression rate of low risk
      prostate cancer. We evaluated the effect of dutasteride on prostate cancer volume
      as assessed by T2-weighted magnetic resonance imaging. MATERIALS AND METHODS: In
      this randomized, double-blind, placebo controlled trial, men with biopsy proven,
      low-intermediate risk prostate cancer (up to Gleason 3 + 4 and PSA up to 15
      ng/ml) who had visible lesion of 0.2 ml or greater on T2-weighted magnetic
      resonance imaging sequences were randomized to daily dutasteride 0.5 mg or
      placebo for 6 months. Lesion volume was assessed at baseline, and 3 and 6 months
      with image guided biopsy to the lesion at study exit. The primary end point was
      the percent reduction in lesion volume over 6 months. This trial was registered
      with the European Clinical Trials register (EudraCT 2009-102405-18). RESULTS: A
      total of 42 men were recruited between June 2010 and January 2012. In the
      dutasteride group, the average volumes at baseline and 6 months were 0.55 and
      0.38 ml, respectively and the average reduction was 36%. In the placebo group,
      the average volumes at baseline and 6 months were 0.65 and 0.76 ml, respectively,
      and the average reduction was -12%. The difference in percent reductions between
      the groups was 48% (95% CI 27.4-68.3, p <0.0001). The most common adverse event
      was deterioration in erectile function, which was 25% in men randomized to
      dutasteride and 16% in men randomized to placebo. CONCLUSIONS: Dutasteride was
      associated with a significant reduction in prostate cancer volume on T2-weighted
      magnetic resonance imaging compared to placebo.

PMID- 27871930
TI  - Reconstruction of Penile Shaft Defects Following Silicone Injection by Bipedicled
      Anterior Scrotal Flap.
AB  - PURPOSE: Numerous causalities, including attempts at penile augmentation with
      silicone or paraffin, can lead to extensive circular penile shaft defects.
      Reconstruction is challenging and skin grafting is a suboptimal option despite
      its widespread use. We present a surgical technique for penile shaft
      reconstruction with a bipedicled anterior scrotal flap. MATERIALS AND METHODS: A
      retrospective data analysis was performed of patients treated for symptomatic
      penile siliconomas who underwent subsequent penile reconstruction with a
      bipedicled anterior scrotal flap between 2010 and 2015. The surgical technique is
      described and depicted in detail. RESULTS: A total of 43 men were treated with
      radical circular excision of penile siliconomas and extensive shaft defects were
      reconstructed with a bipedicled anterior scrotal flap. Mean +/- SD age was 36.95
      +/- 11.27 years, mean followup duration was 10.69 +/- 9.54 months and mean
      operative time was 2.53 +/- 0.46 hours. The operation proved uneventful in all
      cases. Only minor complications were observed, such as partial necrosis in 9% of
      patients, hematoma of the donor site in 12% and partial wound disruption in 19%.
      The mean patient satisfaction score was 4.37 on a scale of 1 to 5. All patients
      reported postoperative erection ability and the ability to achieve sexual
      intercourse. CONCLUSIONS: We present a surgical technique to reconstruct
      extensive penile shaft defects with an axial scrotal flap, which provides well
      vascularized coverage with comparable donor skin quality and thickness. The
      results are associated with minor donor site morbidity, good functional and
      aesthetic outcomes, and high patient satisfaction.

PMID- 27871929
TI  - Past, Present and Future of Chemodenervation with Botulinum Toxin in the
      Treatment of Overactive Bladder.
AB  - PURPOSE: We systematically reviewed preclinical and clinical studies on bladder
      chemodenervation with onabotulinumtoxin A to highlight current limitations and
      future drug delivery approaches. MATERIALS AND METHODS: We identified peer
      reviewed basic and clinical research studies of onabotulinumtoxin A in the
      treatment of neurogenic bladder and refractory idiopathic overactive bladder
      published between March 2000 and March 2016. Paired investigators independently
      screened 125 English language articles to identify controlled studies on
      onabotulinumtoxin A administration in the MEDLINE(r) database and abstracts
      presented at annual American Urological Association meetings. The review yielded
      an evidence base of more than 50 articles relevant to the approach of injection
      free onabotulinumtoxin A chemodenervation. RESULTS: The efficacy and safety of
      intradetrusor injection of onabotulinumtoxin A for the treatment of overactive
      bladder are sensitive to injection volume and depth, and this issue has motivated
      researchers to study injection-free modes of drug delivery into the bladder.
      Urothelial denudation with protamine sulfate or dimethyl sulfoxide, liposome
      encapsulated onabotulinumtoxin A and other physical approaches are being studied
      to increase toxin permeability and avoid intradetrusor injections. Liposome
      encapsulated onabotulinumtoxin A enhances toxin activity while reducing its toxin
      degradation. The safety and efficacy of liposome encapsulated onabotulinumtoxin A
      were tested in a multicenter, placebo controlled study. Although this treatment
      successfully reduced urinary frequency and urgency, it did not significantly
      reduce urgency urinary incontinence episodes. CONCLUSIONS: Intradetrusor
      injection of onabotulinumtoxin A is a safe and effective treatment as reported in
      several large multicenter, randomized controlled trials. Injection of the toxin
      into the bladder wall impairs afferent and efferent nerves, but injection-free
      drug delivery approaches only impair the bladder afferent nerves. Further studies
      are needed to develop better drug delivery platforms that overcome the drawbacks
      of intradetrusor injection, increase patient acceptance and reduce treatment
      costs.

PMID- 27871931
TI  - The Numbers Don't Speak for Themselves: Biochemical Values Associated With
      Pressure Ulcer Healing in Patients With Advanced Illness.

PMID- 27871932
TI  - S100A10 Regulates ULK1 Localization to ER-Mitochondria Contact Sites in IFN-gamma
      Triggered Autophagy.
AB  - During the process of autophagy, the autophagy-related proteins are translocated
      to autophagosome formation sites. Here, we demonstrate that S100A10 is required
      for ULK1 localization to autophagosome formation sites. Silencing of S100A10
      reduces IFN-gamma-induced autophagosome formation. We also determined the role of
      annexin A2 (ANXA2), a binding partner of S100A10, which has been reported to
      promote phagophore assembly. Silencing of ANXA2 reduced S100A10 expression.
      However, overexpression of S100A10 in ANXA2-silenced cells was still able to
      enhance autophagosome formation, suggesting that ANXA2 regulates IFN-gamma
      induced autophagy through S100A10. We also observed that S100A10 interacted with
      ULK1 after IFN-gamma stimulation, and S100A10 knockdown prevented ULK1
      localization to autophagosome formation sites. Finally, the release of high
      mobility group protein B1, one of the functions mediated by IFN-gamma-induced
      autophagy, was inhibited in S100A10 knockdown cells. These results elucidate the
      importance of S100A10 in autophagosome formation and reveal the relationship
      between S100A10 and ULK1 in IFN-gamma-induced autophagy.

PMID- 27871934
TI  - v-Src-induced nuclear localization of YAP is involved in multipolar spindle
      formation in tetraploid cells.
AB  - The protein-tyrosine kinase, c-Src, is involved in a variety of signaling events,
      including cell division. We have reported that v-Src, which is a mutant variant
      of the cellular proto-oncogene, c-Src, causes delocalization of Aurora B kinase,
      resulting in a furrow regression in cytokinesis and the generation of
      multinucleated cells. However, the effect of v-Src on mitotic spindle formation
      is unknown. Here we show that v-Src-expressing HCT116 and NIH3T3 cells undergo
      abnormal cell division, in which cells separate into more than two cells. Upon v
      Src expression, the proportion of multinucleated cells is increased in a time
      dependent manner. Flow cytometry analysis revealed that v-Src increases the
      number of cells having a >=4N DNA content. Microscopic analysis showed that v-Src
      induces the formation of multipolar spindles with excess centrosomes. These
      results suggest that v-Src induces multipolar spindle formation by generating
      multinucleated cells. Tetraploidy activates the tetraploidy checkpoint, leading
      to a cell cycle arrest of tetraploid cells at the G1 phase, in which the nuclear
      exclusion of the transcription co-activator YAP plays a critical role. In
      multinucleated cells that are induced by cytochalasin B and the Plk1 inhibitor,
      YAP is excluded from the nucleus. However, v-Src prevents this nuclear exclusion
      of YAP through a decrease in the phosphorylation of YAP at Ser127 in
      multinucleated cells. Furthermore, v-Src decreases the expression level of p53,
      which also plays a critical role in the cell cycle arrest of tetraploid cells.
      These results suggest that v-Src promotes abnormal spindle formation in at least
      two ways: generation of multinucleated cells and a weakening of the tetraploidy
      checkpoint.

PMID- 27871935
TI  - A Sonic hedgehog coreceptor, BOC regulates neuronal differentiation and neurite
      outgrowth via interaction with ABL and JNK activation.
AB  - Neurite outgrowth is a critical step for neurogenesis and remodeling synaptic
      circuitry during neuronal development and regeneration. An immunoglobulin
      superfamily member, BOC functions as Sonic hedgehog (Shh) coreceptor in canonical
      and noncanonical Shh signaling in neuronal development and axon
      outgrowth/guidance. However signaling mechanisms responsible for BOC action
      during these processes remain unknown. In our previous studies, a multiprotein
      complex containing BOC and a closely related protein CDO promotes myogenic
      differentiation through activation of multiple signaling pathways, including non
      receptor tyrosine kinase ABL. Given that ABL and Jun. N-terminal kinase (JNK) are
      implicated in actin cytoskeletal dynamics required for neurogenesis, we
      investigated the relationship between BOC, ABL and JNK during neuronal
      differentiation. Here, we demonstrate that BOC and ABL are induced in P19
      embryonal carcinoma (EC) cells and cortical neural progenitor cells (NPCs) during
      neuronal differentiation. BOC-depleted EC cells or Boc-/- NPCs exhibit impaired
      neuronal differentiation with shorter neurite formation. BOC interacts with ABL
      through its putative SH2 binding domain and seems to be phosphorylated in an ABL
      activity-dependent manner. Unlike wildtype BOC, ABL-binding defective BOC mutants
      exhibit impaired JNK activation and neuronal differentiation. Finally, Shh
      treatment enhances JNK activation which is diminished by BOC depletion. These
      data suggest that BOC interacts with ABL and activates JNK thereby promoting
      neuronal differentiation and neurite outgrowth.

PMID- 27871933
TI  - A Molecular Prospective for HIRA Complex Assembly and H3.3-Specific Histone
      Chaperone Function.
AB  - Incorporation of variant histone sequences, in addition to post-translational
      modification of histones, serves to modulate the chromatin environment. Different
      histone chaperone proteins mediate the storage and chromatin deposition of
      variant histones. Although the two non-centromeric histone H3 variants, H3.1 and
      H3.3, differ by only 5 aa, replacement of histone H3.1 with H3.3 can modulate the
      transcription for highly expressed and developmentally required genes, lead to
      the formation of repressive heterochromatin, or aid in DNA and chromatin repair.
      The human histone cell cycle regulator (HIRA) complex composed of HIRA,
      ubinuclein-1, CABIN1, and transiently anti-silencing function 1, forms one of the
      two complexes that bind and deposit H3.3/H4 into chromatin. A number of recent
      biochemical and structural studies have revealed important details underlying how
      these proteins assemble and function together as a multiprotein H3.3-specific
      histone chaperone complex. Here, we present a review of existing data and present
      a new model for the assembly of the HIRA complex and for the HIRA-mediated
      incorporation of H3.3/H4 into chromatin.

PMID- 27871936
TI  - COMMD9 promotes TFDP1/E2F1 transcriptional activity via interaction with TFDP1 in
      non-small cell lung cancer.
AB  - COMMD protein family is an evolutionarily conserved gene family implicated in a
      number of critical processes including inflammation, copper homeostasis, sodium
      balance, endosomal sorting and cancer. In an effort to profile the expression
      pattern of COMMD family in several non-small cell lung cancer (NSCLC) cell lines,
      we found that compared with that in human bronchial epithelial (HBE) cells, the
      mRNA expression levels of five COMMD genes including COMMD3, COMMD4, COMMD5,
      COMMD6 and COMMD8 were significantly down-regulated, whereas COMMD9 was up
      regulated in NSCLC cell lines. Here we reported that the expression of COMMD9
      protein was significantly increased in various NSCLC cell lines and tissue
      samples. SiRNA-induced knocking down of COMMD9 inhibited proliferation and
      migration, arrested cell cycle at G1/S transition and induced autophagy in NSCLC
      cells. Mechanistically, COMMD9 interacted with the TFDP1 through COMM domain, and
      DNA-binding domain of TFDP1 was required for this interaction. Moreover,
      decreased expression COMMD9 attenuated TFDP1/E2F1 activation accompanied with
      enhanced p53 signaling pathway. Taken together, these findings demonstrate that
      COMMD9 participates in TFDP1/E2F1 activation and plays a critical role in non
      small cell lung cancer.

PMID- 27871937
TI  - Elevated levels of alpha-synuclein blunt cellular signal transduction downstream
      of Gq protein-coupled receptors.
AB  - Alpha-synuclein is central to Parkinson's disease pathogenesis and pathology,
      however its precise functions are still unclear. It has been shown to bind both
      PLCbeta1 and MAPKs, but how this property influences the downstream signaling of
      Gq protein-coupled receptors has not been elucidated. Here we show that
      recombinant expression of alpha-synuclein in human neuroblastoma cells enhances
      cellular levels of PLCbeta1 but blunts its signaling pathway, preventing the
      agonist-dependent rise of cytoplasmic Ca2+. In addition, overexpressing alpha
      synuclein abolishes the activation of ERK1/2 upon agonist stimulation, indicating
      an upstream action in the signal transduction pathway. This data demonstrates
      that alpha-synuclein, when recombinantly expressed, interferes with the normal
      signaling of Gq-protein coupled receptors, which are then dysfunctional. Since
      many neurotransmitter systems utilize these receptor signaling pathways to
      mediate different abilities affected in Parkinson's disease, we argue this novel
      perspective might be helpful in designing treatment strategies for some of the
      non-motor symptoms in Parkinson's disease and synucleinopathies.

PMID- 27871938
TI  - The role of Gpi-anchored axonal glycoproteins in neural development and
      neurological disorders.
AB  - This review article focuses on the Contactin (CNTN) subset of the Immunoglobulin
      supergene family (IgC2/FNIII molecules), whose components share structural
      properties (the association of Immunoglobulin type C2 with Fibronectin type III
      domains), as well as a general role in cell contact formation and axonal growth
      control. IgC2/FNIII molecules include 6 highly related components (CNTN 1-6),
      associated with the cell membrane via a Glycosyl Phosphatidyl Inositol (GPI)
      containing lipid tail. Contactin 1 and Contactin 2 share ~50 (49.38)% identity at
      the aminoacid level. They are components of the cell surface, from which they may
      be released in soluble forms. They bind heterophilically to multiple partners in
      cis and in trans, including members of the related L1CAM family and of the
      Neurexin family Contactin-associated proteins (CNTNAPs or Casprs). Such
      interactions are important for organising the neuronal membrane, as well as for
      modulating the growth and pathfinding of axon tracts. In addition, they also
      mediate the functional maturation of axons by promoting their interactions with
      myelinating cells at the nodal, paranodal and juxtaparanodal regions. Such
      interactions also mediate differential ionic channels (both Na+ and K+)
      distribution, which is of critical relevance in the generation of the peak-shaped
      action potential. Indeed, thanks to their interactions with Ankyrin G, Na+
      channels map within the nodal regions, where they drive axonal depolarization.
      However, no ionic channels are found in the flanking Contactin1-containing
      paranodal regions, where CNTN1 interactions with Caspr1 and with the Ig
      superfamily component Neurofascin 155 in cis and in trans, respectively, build a
      molecular barrier between the node and the juxtaparanode. In this region K+
      channels are clustered, depending upon molecular interactions with Contactin 2
      and with Caspr2. In addition to these functions, the Contactins appear to have
      also a role in degenerative and inflammatory disorders: indeed Contactin 2 is
      involved in neurodegenerative disorders with a special reference to the Alzheimer
      disease, given its ability to work as a ligand of the Alzheimer Precursor Protein
      (APP), which results in increased Alzheimer Intracellular Domain (AICD) release
      in a gamma-secretase-dependent manner. On the other hand Contactin 1 drives Notch
      signalling activation via the Hes pathway, which could be consistent with its
      ability to modulate neuroinflammation events, and with the possibility that
      Contactin 1-dependent interactions may participate to the pathogenesis of the
      Multiple Sclerosis and of other inflammatory disorders.

PMID- 27871939
TI  - Cell-cell communication mediated by the CAR subgroup of immunoglobulin cell
      adhesion molecules in health and disease.
AB  - The immunoglobulin superfamily represents a diverse set of cell-cell contact
      proteins and includes well-studied members such as NCAM1, DSCAM, L1 or the
      contactins which are strongly expressed in the nervous system. In this review we
      put our focus on the biological function of a less understood subgroup of Ig-like
      proteins composed of CAR (coxsackievirus and adenovirus receptor), CLMP (CAR-like
      membrane protein) and BT-IgSF (brain and testis specific immunoglobulin
      superfamily). The CAR-related proteins are type I transmembrane proteins
      containing an N-terminal variable (V-type) and a membrane proximal constant (C2
      type) Ig domain in their extracellular region which are implicated in homotypic
      adhesion. They are highly expressed during embryonic development in a variety of
      tissues including the nervous system whereby in adult stages the protein level of
      CAR and CLMP decreases, only BT-IgSF expression increases within age. CAR-related
      proteins are concentrated at specialized cell-cell communication sites such as
      gap or tight junctions and are present at the plasma membrane in larger protein
      complexes. Considerable progress has been made on the molecular structure and
      interactions of CAR while research on CLMP and BT-IgSF is at an early stage.
      Studies on mouse mutants revealed biological functions of CAR in the heart and
      for CLMP in the gastrointestinal and urogenital systems. Furthermore, CAR and BT
      IgSF appear to regulate synaptic function in the hippocampus.

PMID- 27871941
TI  - Mimicking the ocular environment for the study of inflammatory posterior eye
      disorders.
AB  - The common inflammatory posterior eye disorders, age-related degeneration and
      glaucoma often lead to irreversible vision loss. Current treatments do not target
      early stages or prevent disease progression. Consequently, the identification of
      biomarkers or early disease models that can accurately mimic the pathological
      processes involved is essential. Although none of the existing models can
      recapitulate all pathological aspects of these disorders, these models have
      revealed new therapeutic targets. Efforts to accurately phenotype eye disorders
      at various disease stages are warranted to generate a 'super' model that can
      replicate the microenvironment of the eye and associated pathological hallmarks
      effectively.

PMID- 27871940
TI  - Bacterial lipoproteins; biogenesis, sorting and quality control.
AB  - Bacterial lipoproteins are a subset of membrane proteins localized on either
      leaflet of the lipid bilayer. These proteins are anchored to membranes through
      their N-terminal lipid moiety attached to a conserved Cys. Since the protein
      moiety of most lipoproteins is hydrophilic, they are expected to play various
      roles in a hydrophilic environment outside the cytoplasmic membrane. Gram
      negative bacteria such as Escherichia coli possess an outer membrane, to which
      most lipoproteins are sorted. The Lol pathway plays a central role in the sorting
      of lipoproteins to the outer membrane after lipoprotein precursors are processed
      to mature forms in the cytoplasmic membrane. Most lipoproteins are anchored to
      the inner leaflet of the outer membrane with their protein moiety in the
      periplasm. However, recent studies indicated that some lipoproteins further
      undergo topology change in the outer membrane, and play critical roles in the
      biogenesis and quality control of the outer membrane. This article is part of a
      Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.

PMID- 27871942
TI  - Computational approaches for modeling and analysis of human-on-chip systems for
      drug testing and characterization.

PMID- 27871943
TI  - Understanding the attitudes and perceptions of vegetarian and plant-based diets
      to shape future health promotion programs.
AB  - Vegetarian diets have become a prominent area of interest. However, little
      research has focused on the attitudes and perceptions on vegetarian diets. The
      purpose of this scoping review was to methodologically search the literature and
      summarize public perceptions and attitudes towards a vegetarian diet. Using the
      information found from this review, the Health Belief Model can be applied to
      shape future health promotion initiatives to move individuals towards a
      vegetarian or plant-based diet. The main findings indicate that vegetarian diets
      are generally perceived in a positive light. There are many barriers to consuming
      this diet such as health concerns, an unwillingness to make dietary changes, and
      an enjoyment of eating meat.

PMID- 27871944
TI  - Predictors of food decision making: A systematic interdisciplinary mapping (SIM)
      review.
AB  - The number of publications on consumer food decision making and its predictors
      and correlates has been steadily increasing over the last three decades. Given
      that different scientific disciplines illuminate this topic from different
      perspectives, it is necessary to develop an interdisciplinary overview. The aim
      of this study is to conduct a systematic interdisciplinary mapping (SIM) review
      by using rapid review techniques to explore the state-of-the-art, and to identify
      hot topics and research gaps in this field. This interdisciplinary review
      includes 1,820 publications in 485 different journals and other types of
      publications from more than ten disciplines (including nutritional science,
      medicine/health science, psychology, food science and technology, business
      research, etc.) across a period of 60 years. The identified predictors of food
      decision making were categorized in line with the recently proposed DONE
      (Determinants Of Nutrition and Eating behavior) framework. After applying
      qualitative and quantitative analyses, this study reveals that most of the
      research emphasizes biological, psychological, and product-related predictors,
      whereas policy-related influences on food choice are scarcely considered.

PMID- 27871945
TI  - Exposure to diet priming images as cues to reduce the influence of unhealthy
      eating habits.
AB  - A key barrier to changing unhealthy eating habits is the current food-rich
      environment. Today, there are many palatable food cues that trigger unhealthy
      eating habits, and once a habit is strongly engrained, it becomes very difficult
      to change. This research examined the effects of diet priming that is a type of
      cueing intervention that activates a dieting goal in a tempting situation and
      thus reduces unhealthy eating behavior in line with the dieting goal. This
      research was conducted both in a laboratory and in two field experiments. In the
      three experiments, participants were randomly assigned to conditions where they
      were either primed by an image of a slim model associated with dieting (priming
      condition) or were presented with an image of an animal unrelated to dieting
      (control condition). The dependent variable was the number of snacks that
      participants took in the laboratory in Study 1 and the number of snacks consumed
      within the next two weeks in a daily setting in Study 2 and 3. The three studies
      showed that unhealthy eating habits strongly affect general eating behavior.
      However, in this research, diet priming changed the influence of unhealthy eating
      habits and resulted in the decrease of unhealthy eating. Exposure to diet priming
      cues moderated the influence of unhealthy eating habits triggered by palatable
      food cues in today's food-rich environment. These findings suggest that diet
      priming can change habitual reactions to temptations associated with unhealthy
      eating. Implications for diet priming as an intervention for unhealthy eating
      habits are discussed herein.

PMID- 27871946
TI  - Trivaric acid, a new inhibitor of PTP1b with potent beneficial effect on
      diabetes.
AB  - AIM: To screen a potential PTP1b inhibitor from the microbial origin-based
      compound library and to investigate the potential anti-diabetic effects of the
      inhibitor in vivo and determine its primary anti-diabetic mechanism in vitro and
      in silico. METHODS: PTP1b inhibitory activity was measured using recombination
      protein as the enzyme and p-NPP as the substrate. The binding of the inhibitor to
      PTP1b was analysed by docking in silico and confirmed by ITC experiments. The
      intracellular signalling pathway was detected by Western blot analysis in HepG2
      cells. The anti-diabetic effects were evaluated using a diabetic mice model in
      vivo. RESULTS: Among 545 microbial origin-based pure compounds tested, trivaric
      acid, a tridepside, was selected as a PTP1B inhibitor exhibiting strong
      inhibitory activity with an IC50 of 173nM. Docking and ITC studies showed that
      trivaric acid was able to spontaneously bind to PTP1b and may inhibit PTP1b by
      blocking the catalytic domain of the phosphatase. Trivaric acid also enhanced the
      ability of insulin to stimulate the IR/IRS/Akt/GLUT2 pathway and increase the
      glucose consumption in HepG2 cells. In diabetic mice, trivaric acid that had been
      encapsulated into Eudrgit L100-5.5 showed significant anti-diabetic effects,
      improving insulin resistance, leptin resistance and lipid profile and weight
      control at doses of 5mg/kg and 50mg/kg. SIGNIFICANCE: Trivaric acid is a
      potential lead compound in the search for anti-diabetic agents targeting PTP1b.

PMID- 27871948
TI  - Vestibular cerebellum of thick-toed geckos (Chondrodactylus turnery GRAY, 1864)
      and C57/BL6N mice after the long-term space flight on the biosatellite BION-M1.
AB  - The aim of this study was to estimate the effects of long-term space flights on
      neuronal and glial cells of the vestibular cerebellum of C57/BL6N mice and thick
      toed geckos (Chondrodactylus turnery GRAY, 1864). The cerebella from 26 mice and
      13 geckos were used in this study. Ten mice and five geckos were flown aboard the
      BION-M1 biosatellite. The other animals were used as controls. We used
      immunohistochemical techniques and classical histological method to reveal cell
      types in the vestibular cerebellum. Nonspecific pathomorphological changes in the
      Purkinje cells (such as chromatolysis, vacuolization and hyperchromatosis) were
      observed in the flight groups. However, these changes are reversible and were
      also found in some neurons in the control groups. In addition, as the vestibular
      cerebellum is an evolutionarily stable structure, thick-toed geckos may be a
      useful model for space flight studies on the vertebrate cerebellum.

PMID- 27871947
TI  - Mechanistic insight into carnosol-mediated pharmacological effects: Recent trends
      and advancements.
AB  - For several decades, bioactive phytochemicals have been appreciated to prevent
      and cure various lethal diseases. Many studies have proven the ability of dietary
      phytochemicals to avoid and retard tumor initiation and progression. Among the
      pharmacologically active moieties, terpenoids are considered one of the most
      important classes. Carnosol, is also a kind of diterpenoid, which known to
      possess a range of therapeutic effects such as anti-cancer, anti-inflammatory,
      and anti-oxidant activities. All these effects are mediated via modulating
      different signaling cascades, including apoptosis regulating molecules
      (Bax/Bcl2), prosurvival-proproliferative molecules (Akt/mTOR, MAPK),
      transcription factors like NF-kappaB, STAT3-6, and steroid receptors, such as
      androgen and estrogen receptors. The present review highlights the recent trends
      and advancements have been done in the field of research by using carnosol.

PMID- 27871949
TI  - Cloning and characterization of fatty acid-binding proteins (fabps) from Japanese
      seabass (Lateolabraxjaponicus) liver, and their gene expressions in response to
      dietary arachidonic acid (ARA).
AB  - In the present study, putative cDNA of five fabp isoforms, i.e., fabp1, fabp2,
      fabp3, fabp4, and fabp7, was cloned and characterized from the liver of Japanese
      seabass (Lateolabrax japonicus), and their expression in response to diets with
      different arachidonic acid (ARA) levels (0.05%, 0.22%, 0.37%, 0.60%, 1.38% and
      2.32% of dry matter) was investigated following a feeding trial. The Japanese
      seabass fabps showed high identity to their orthologs in other fish species and
      mammals. However, a specific fabp of Japanese seabass showed much lower identity
      to other Japanese seabass fabps. fabp1 has high expressions in liver and
      intestine, whereas fabp2 is mainly expressed in the gastrointestinal tract. The
      highest expression level of fabp3, fabp4, and fabp7 was observed in muscle, eye,
      and liver respectively. Different tissue expression patterns of fabp2, fabp4, and
      fabp7 between Japanese seabass and other teleost may indicate specific
      evolutionary Fabp functions in Japanese seabass. Moderate levels of dietary ARA
      (0.37-0.60%) enhanced the gene expressions of fabp1 in liver and intestine, fabp2
      in intestine, and fabp3 in intestine, whereas excess dietary ARA levels (1.38
      2.323%) were ineffective. The highest level of dietary ARA (2.32%) increased only
      the expression of fabp3 in muscle compared to the control diet. Gene expressions
      of fabp3 and fabp7 in liver, and fabp4 in liver, intestine, and muscle were not
      significantly influenced by dietary ARA. To our knowledge, this is the first
      study investigating the regulation of fabp expressions by dietary ARA.

PMID- 27871950
TI  - Increased expression of HERPUD1 involves in neuronal apoptosis after
      intracerebral hemorrhage.
AB  - Homocysteine-inducible endoplasmic reticulum stress-inducible ubiquitin-like
      domain member 1 protein (HERPUD1) is involved in endoplasmic reticulum stress
      response. Immense amounts of research showed HERPUD1 plays multiple roles in
      various models. In this work, we explored the role of HERPUD1 during the
      pathophysiological processes of intracerebral hemorrhage (ICH). Rat ICH model was
      established and verified by behavioral test. Western blot and
      immunohistochemistry revealed a significant up-regulation of HERPUD1 expression
      around the hematoma after ICH. Besides, the expression of cytochrome c (cyt c)
      and active caspase-3 increased accompanied to HERPUD1 expression. Double-labeled
      immunofluorescence indicated HERPUD1 mainly colocalized with neurons. Further
      study showed HERPUD1 silence brought about up-regulation of apoptosis markers
      including cyt c and active caspase-3 coupled with increased cell apoptosis in
      vitro model. All these findings suggested that HERPUD1 might play a protective
      role in ICH-induced neuronal apoptosis in rat models.

PMID- 27871952
TI  - "When I Wore a Younger Man's Clothes".

PMID- 27871951
TI  - Regulation of merlin by protein phosphatase 1-TIMAP and EBP50 in endothelial
      cells.
AB  - Merlin (moesin-ezrin-radixin like protein), the product of neurofibromatosis type
      2 gene, was primarily recognized as a tumor suppressor, but it also functions as
      a membrane-cytoskeletal linker and regulator of multiple signaling pathways. The
      activity and localization of merlin is regulated by head to tail folding that is
      controlled by phosphorylation of the Ser518 side chain. Merlin localizes in the
      nucleus when the Ser518 side chain is not phosphorylated, while the
      phosphorylated form is present in the cytoplasm and the plasma membrane. In this
      work interactions and their impact on the subcellular localization and
      phosphorylation state of the Ser518 side chain of merlin were investigated in
      endothelial cells. It is shown that merlin (dephospho-Ser518 form) interacts in
      the nucleus of endothelial cells with the scaffolding protein EBP50, a member of
      the Na+/H+exchanger regulatory factor family. Upon EBP50 depletion, merlin
      translocated from the nucleus, suggesting that binding of merlin to EBP50 is
      critical in the nuclear localization of merlin. Along with the translocation, the
      phosphorylation level of phospho-Ser518-merlin was increased in EBP50 depleted
      cells. TIMAP (TGFbeta-inhibited membrane-associated protein), a type 1 protein
      phosphatase (PP1) regulatory subunit, was newly recognized as an interacting
      partner for merlin. Domain mapping using truncated mutant forms in GST pull down
      revealed that the N-terminal half of TIMAP (aa 1-290) and the FERM domain of
      merlin are the regions responsible for the interaction.The catalytic subunit of
      PP1 (PP1c) was present in all merlin-TIMAP pull down or immunoprecipitation
      samples demonstrating that merlin actually interacts with the PP1c-TIMAP
      holoenzyme. On the other hand, from TIMAP depleted cells, without its targeting
      protein, PP1c could not bind to merlin. Also, when the phosphatase activity of
      PP1c-TIMAP was inhibited either with depletion of TIMAP or by treatment of the
      cells with specific PP1 inhibitor, there was an increase in the amount of phospho
      Ser518 form of merlin in the membrane of the cells. These data strongly suggest
      that the PP1c-TIMAP- complex dephosphorylates phospho-Ser518-merlin. ECIS
      measurements indicate that phospho-merlin accelerates in vitro wound healing of
      the endothelial monolayer. In conclusion, in endothelial cells, EBP50 is required
      for the nuclear localization of merlin and the PP1c-TIMAP holoenzyme plays an
      important role in the dephosphorylation of merlin on its Ser518 side chain, which
      influence cell migration and proliferation.

PMID- 27871953
TI  - Prevalence of Female Sexual Dysfunction Among Premenopausal Women: A Systematic
      Review and Meta-Analysis of Observational Studies.
AB  - INTRODUCTION: Epidemiologic research in female sexual dysfunction (FSD) has
      gained momentum in recent years, particularly in clinical populations and in
      menopausal women. However, sexual dysfunction also affects premenopausal women in
      general populations. Previous literature reviews have been unable to quantify the
      burden of FSD in general populations. This has been due in part to different
      definitions of dysfunction, heterogeneous study design, and the wide variety of
      measurement tools used. AIM: To provide a meta-analytical estimate of the
      prevalence of FSD in premenopausal women. METHODS: Observational studies that
      assessed the prevalence of FSD in premenopausal women were systematically sought
      in relevant databases (January 2000 through July 2014). Publications that
      reported the prevalence rate for at least one domain of FSD were included. A meta
      analysis of prevalence rates was performed and a meta-regression was used to
      analyze factors of study design. MAIN OUTCOME MEASURES: Estimated prevalence
      rates of FSD and its domains (hypoactive sexual desire disorder, sexual aversion
      disorder, female sexual arousal disorder, lubrication difficulties, female
      orgasmic disorder, and pain disorders). RESULTS: After screening 9,292 results,
      440 publications were retrieved for full-text review. Of these, 135 studies were
      included in the systematic review. Ninety-five of these studies were assessed
      further in a meta-analysis. There was substantial heterogeneity among studies.
      The prevalence of FSD in premenopausal women was estimated to be 40.9% (95% CI =
      37.1-44.7, I2 = 99.0%). Prevalence rates of individual sexual disorders ranged
      from 20.6% (lubrication difficulties) to 28.2% (hypoactive sexual desire
      disorder). Further analyses showed significantly higher rates of FSD in studies
      in Africa, studies that used non-validated assessment tools, and studies without
      pharmaceutical funding. CONCLUSION: Prevalence estimates of FSD vary
      substantially. Nonetheless, results show that FSD is a significant public health
      problem that affects 41% of premenopausal women around the globe. More research
      and improved standardization are needed in this field.

PMID- 27871954
TI  - Surgical Management for Pelvic Organ Prolapse and Its Impact on Sexual Function.
AB  - INTRODUCTION: Female sexual function is complex, incorporating physical,
      emotional, and psychological factors. Pelvic organ prolapse, descent of the
      pelvic organs to or through the vaginal opening, is a common condition that
      affects quality of life, including sexual function. Symptomatic prolapse is most
      commonly treated with reconstructive surgery. AIM: To address the surgical
      management of pelvic organ prolapse and its impact on sexual function and include
      recommendations for evaluating sexual function, use of validated questionnaires
      to assess function, preoperative counseling, and postoperative follow-up.
      METHODS: A literature search was performed for articles evaluating sexual
      function after pelvic organ prolapse surgery. Priority was given to larger
      studies, including systematic reviews, and use of validated questionnaires. MAIN
      OUTCOME MEASURES: The main outcome was postoperative sexual function after pelvic
      organ prolapse repair. RESULTS: Multiple surgical approaches are used for the
      treatment of pelvic organ prolapse, including native tissue and grafted repairs.
      An evaluation of sexual function preoperatively is necessary to decide on type of
      surgery and to establish appropriate postoperative expectations. Postoperatively,
      most patients report sexual function as improved or unchanged. CONCLUSION:
      Thorough preoperative counseling allows patients and their physicians to develop
      appropriate, individualized treatment plans for pelvic organ prolapse that
      consider women's preoperative sexual function and sexual function goals.

PMID- 27871955
TI  - Challenges to Practicing Sexual Medicine in the Middle East.
AB  - INTRODUCTION: The Middle East is a vast region that includes the Arabian
      Peninsula, Turkey, Iran, the Levant, and North Africa. Some of the world's
      earliest civilizations appeared in this region and major religions such as
      Judaism, Christianity, and Islam originated there. It is an influential region in
      politics, economy, and resources, but it remains largely enigmatic to those
      outside the region. The various ethnicities, religions, traditions, and customs
      in the region have made it unique and diverse at the same time. Among the most
      controversial topics that have emerged about the Middle East is sex and
      sexuality. Images of women wearing veils and black abayas come to mind. However,
      in this region, sexual freedoms such as polygyny are permitted. It is in these
      settings that are unlike anywhere else that regional sexual medicine physicians
      must practice and produce results. AIMS: To present some factors challenging to
      the practice of sexual medicine in the Middle East. METHODS: The literature was
      reviewed for studies that addressed sexual medicine in the Middle East. This was
      supplemented by studies that investigated certain patterns of practice and
      behaviors that are often encountered in medical practice in the region. MAIN
      OUTCOME MEASURES: Factors contributing to the difficulties in practice faced by
      sexual medicine physicians in the Middle East. RESULTS: Several societal,
      environmental, and patient- and physician-related factors were identified.
      CONCLUSION: It can be particularly challenging to practice sexual medicine in the
      Middle East. However, the region needs qualified sexual medicine specialists to
      debunk many myths concerning sexuality and sexual health, in addition to the day
      to-day practice of this specialty.

PMID- 27871956
TI  - Evidence for Masturbation and Prostate Cancer Risk: Do We Have a Verdict?
AB  - INTRODUCTION: Prostate cancer (PCa) is one of the leading causes of cancer death
      in men and remains one of the most diagnosed malignancies worldwide. Ongoing
      public health efforts continue to promote protective factors, such as diet,
      physical activity, and other lifestyle modifications, against PCa development.
      Masturbation is a nearly universal safe sexual activity that transcends societal
      boundaries and geography yet continues to be met with stigma and controversy in
      contemporary society. Although previous studies have examined associations
      between sexual activity and PCa risk, anecdotal relations have been suggested
      regarding masturbation practice and PCa risk. AIM: To provide a summary of the
      published literature and examine the contemporary evidence for relations between
      masturbation practice and PCa risk. METHODS: A survey of the current literature
      using seven academic electronic databases was conducted using search terms and
      key words associated with masturbation practice and PCa risk. MAIN OUTCOME
      MEASURES: The practice of masturbation and its relation to PCa risk. RESULTS: The
      literature search identified study samples (n = 16) published before October
      2015. Sample inclusions varied by study type, sample size, and primary objective.
      Protective relations (n = 7) between ejaculation through masturbation and PCa
      risk were reported by 44% of the study sample. Age range emerged as a significant
      variable in the relation between masturbation and PCa. CONCLUSION: Findings
      included relations among masturbation, ejaculation frequency, and age range as
      individual factors of PCa risk. No universally accepted themes were identified
      across the study sample. Throughout the sample, there was insufficient agreement
      in survey design and data reporting. Potential avenues for new research include
      frequency of ejaculation and age range as covarying factors that could lead to
      more definitive statements about masturbation practice and PCa risk.

PMID- 27871957
TI  - Tramadol Abuse and Sexual Function.
AB  - INTRODUCTION: Tramadol exhibits an effect profile similar to that of opioid
      agonists, and tramadol abuse seems to be a problem for a number of countries. The
      relationship between tramadol and sexual function appears to be controversial.
      Men with premature ejaculation (PE) may benefit from taking tramadol off label;
      however, these patients live "on a knife's edge" and are exquisitely sensitive to
      develop other sexual dysfunctions. AIM: To review the literature regarding the
      problem of tramadol abuse and its relationship with sexual function. METHODS: We
      searched electronic databases from 1977 to September 2015, including PubMed
      MEDLINE, EMBASE, EBCSO Academic Search Complete, Cochrane Systematic Reviews
      Database, and GoogleScholar using the following key words: tramadol, sexual
      functions, and sexual dysfunction. MAIN OUTCOME MEASURE: To define the supposed
      benefits and the potential risks of tramadol on different sexual functions
      including ejaculation, orgasm, erection, desire, and testosterone levels.
      RESULTS: Although tramadol is thought to have low abuse and dependence potentials
      worldwide, its abuse has become a serious problem in many countries, particularly
      in the Middle East, Africa, and West Asia. The benefit of tramadol in PE was
      reported in 11 clinical trials, evaluated by 6 systematic reviews, 3 of which
      pooled data in a meta-analysis. The evidence base on erectile dysfunction,
      decreased libido, hypogonadism, anorgasmia, and risky sexual behaviors in
      patients abusing tramadol is inadequate. CONCLUSIONS: Tramadol may offer a useful
      intervention for treating PE. As all primary studies had suffered from selection,
      allocation, performance, or assessment bias, additional rigorous well-designed
      controlled trials are warranted to further investigate the potential long-term
      risks of tramadol and to determine the safe and the effective minimum daily dose.
      Clinical research on drug abuse and sexual dysfunction is an emerging field. To
      date, small numbers of studies have been performed and further studies are
      warranted.

PMID- 27871958
TI  - Current Perspectives on Stem Cell Therapy for Erectile Dysfunction.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common sexual disorder that affects
      the lives of millions of male patients and their partners. Various medical and
      surgical therapies exist, with the most common being oral intake of
      phosphodiesterase 5 inhibitors. One therapeutic strategy in preclinical
      development to treat ED is stem cell transplantation. AIM: To examine the studies
      that have investigated stem cells for the treatment of ED. METHODS: A literature
      review was performed through PubMed focusing on stem cells and ED. MAIN OUTCOME
      MEASURES: An assessment of different types of stem cells and how they may be
      applied therapeutically in the treatment of ED. RESULTS: The stem cell types that
      have been investigated for the treatment of ED include bone marrow-derived
      mesenchymal, adipose-derived, muscle-derived, testes, urine-derived, neural
      crest, and endothelial progenitor. Depending on the cell type, research has
      demonstrated that with transplantation, stem cells exert a paracrine effect on
      penile tissue, and can differentiate into smooth muscle, endothelium, and
      neurons. CONCLUSION: Multiple stem cell lines are currently being studied for
      their potential to treat ED. To date, stem cells have proven safe and effective
      in both animal and human models of ED. More research is needed to understand
      their full therapeutic potential.

PMID- 27871959
TI  - Intracavernous Injections in Spinal Cord Injured Men With Erectile Dysfunction, a
      Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Despite improvements in the care of patients after spinal cord
      injury (SCI), permanent impairment of locomotion, sensation, and autonomic
      function remains a major hurdle. After the acute stage of injury, recovering
      sexual function is a high priority. AIM: To review the efficacy of intracavernous
      injections (ICIs) in men with SCI and to identify prognostic factors affecting
      the efficacy of ICIs in this population. METHODS: Systematic review of the
      literature was conducted using the PubMed-Medline, Embase, EBSCO, Web of Science,
      and Cochrane Library databases. The literature search was restricted to articles
      published in English, French, and Spanish up to November 2014 using the key words
      alprostadil, papaverine, moxisylite, alpha-blocking agent, phentolamine,
      intracavernous injection, spinal cord injuries, paraplegia, quadriplegia, and
      erectile dysfunction. Studies involving patients with SCI and erectile
      dysfunction treated with ICIs of alprostadil, papaverine, and alpha-blocking
      agents, including retrospective and prospective cohorts, population studies, and
      randomized controlled trials, were included. MAIN OUTCOME MEASURE: Overall
      response rate to ICI for erectile dysfunction in patients with SCI. RESULTS: Of
      283 studies identified, 23 involved 713 patients with SCI. ICIs resulted in
      successful erections in 88% of patients (n = 713, 95% CI = 83%-92%). Erections
      were obtained in 93% of patients (n = 101, 95% CI = 83%-99%) with the combination
      of papaverine and phentolamine, in 91% (n = 274, 95% CI = 78%-97%) with
      papaverine alone, and in 80% (n = 119, 95% CI = 64%-90%) with alprostadil. Type
      of injected drug, doses, level of injury (complete or incomplete), extent of
      injury, age, time since injury, and persistence or transience of erections were
      evaluated, but statistical analysis could not identify specific factors
      predictive of a response to ICI. CONCLUSION: ICIs are an effective treatment of
      erectile dysfunction in men with SCI. No predictive factor for efficacy could be
      identified. Studies comparing the response to ICI in upper vs lower motor neuron
      lesions could improve our understanding of ICI failure.

PMID- 27871960
TI  - Useful Implications of Low-dose Long-term Use of PDE-5 Inhibitors.
AB  - INTRODUCTION: Phosphodiesterase type 5 (PDE-5) hydrolyzes cyclic guanylate
      monophosphate (cGMP) specifically to 5' GMP, promoting successful corporeal
      vascular relaxation and penile erection during sexual stimulation. Oral PDE-5
      inhibitors such as sildenafil, vardenafil, tadalafil, and avanafil have provided
      noninvasive, effective, well-tolerated treatment for erectile dysfunction (ED)
      patients and, at the same time, stimulated both academic and clinical interests.
      Lately, some oral PDE-5 inhibitors were released as low-dose preparations with
      the concept of potential daily administration and long-term use. AIM: To
      highlight the possible potential implications of low-dose long-term use of PDE-5
      inhibitors. METHOD: A systematic review was carried out until December 2015 based
      on a search of all concerned articles in MEDLINE, medical subjects heading (MeSH)
      databases, Scopus, The Cochrane Library, EMBASE, and CINAHL databases without
      language restriction. Key words used to assess the outcome and estimates for
      concerned associations were: PDE-5 inhibitors; erectile dysfunction; low-dose;
      long-term; sildenafil; tadalafil; vardenafil; avanafil. MAIN OUTCOME MEASURES:
      Demonstrating different implications for low-dose long-term use of PDE-5
      inhibitors. RESULTS: Low-dose and/or long-term use of PDE-5 inhibitors was shown
      to put forth beneficial sound effects in different medical implications with
      potentials that could be extended for different utilities. These implications
      included sexual, urogenital, cardiovascular, pulmonary, cutaneous,
      gastrointestinal, and reproductive, as well as neurological disorders. However,
      it is evident that most potential appliances were carried out experimentally on
      preclinical studies with off-label indications. CONCLUSION: Making use of and
      exploring low-dose and/or long-term use of several PDE-5 inhibitors for their
      possible implications seem to be valuable in different medical disorders.
      Increased knowledge of the drug characteristics, comparative treatment regimens,
      optimal prescribing patterns, and well-designed clinical trials are needed before
      these agents can be recommended for use.

PMID- 27871961
TI  - A History of the Penile Implant to 1974.

PMID- 27871962
TI  - Penile Implant: Review of a "No-Touch" Technique.
AB  - INTRODUCTION: Over 25% of the more than 725,000 cases of nosocomial infection in
      the United States are related to an implantable device. Despite the standard
      typical strategies available, infection rates for breast implants, cerebrospinal
      shunts, and penile implants remain unacceptably high. This paper will review use
      of a "no-touch" technique in varied surgical procedures from orthopedic fracture
      repair, cerebrospinal fluid shunt placement, and breast
      reconstruction/augmentation to penile prosthesis implantation. AIM: One of our
      aims was to investigate whether the "no-touch" concept was unique to the field of
      penile implants and if similar results were obtained in other subspecialties. The
      other was to examine whether the low infection rate initially obtained with the
      "no-touch" technique was maintained for a larger number of penile implant
      procedures. METHODS: The literature was reviewed for the use of the "no-touch"
      technique in procedures as varied as orthopedic fracture repair, cerebrospinal
      fluid shunt placement, breast reconstruction/augmentation, and penile prosthesis
      implantation. In addition, a single surgeon's experience with 3342 penile implant
      surgeries with and without the use of the "no-touch" technique was reviewed. MAIN
      OUTCOME MEASURE: Penile implant infection rate was examined for 3342 consecutive
      cases between January 2002 and December 2014. Infection of standard technique was
      compared with rate of infection with antibiotic impregnated devices and starting
      in 2006 with the addition of the "no-touch" enhancement. RESULTS: Literature
      review revealed that the "no-touch" technique decreased postoperative cerebral
      shunt infection from 9.1% to 2.9%. Breast implant reconstruction surgical site
      infection decreased from 19% to none with the "no-touch" technique. Penile
      implant infection rate fell from 5.3% in 2002 to 1.99% with the use of antibiotic
      impregnated devices and to 0.44% with the addition of the "no-touch" technique.
      CONCLUSION: Use of a "no-touch" technique involving a mechanical barrier makes a
      difference in preventing infection of an implantable device.

PMID- 27871963
TI  - Uptake of silica nanoparticles in the brain and effects on neuronal
      differentiation using different in vitro models.
AB  - Nanomedicine offers a promising tool for therapies of brain diseases, but they
      may be associated with potential adverse effects. The aim of this study was to
      investigate the uptake of silica-nanoparticles engineered for laser-tissue
      soldering in the brain using SH-SY5Y cells, dissociated and organotypic slice
      cultures from rat hippocampus. Nanoparticles were predominantly taken up by
      microglial cells in the hippocampal cultures but nanoparticles were also found in
      differentiated SH-SY5Y cells. The uptake was time- and concentration-dependent in
      primary hippocampal cells. Transmission electron microscopy experiments
      demonstrated nanoparticle aggregates and single particles in the cytoplasm.
      Nanoparticles were found in the endoplasmic reticulum, but not in other cellular
      compartments. Nanoparticle exposure did not impair cell viability and
      neuroinflammation in primary hippocampal cultures at all times investigated.
      Neurite outgrowth was not significantly altered in SH-SY5Y cells, but the
      neuronal differentiation markers indicated a reduction in neuronal
      differentiation induction after nanoparticle exposure.

PMID- 27871964
TI  - Caloric restriction - A promising anti-cancer approach: From molecular mechanisms
      to clinical trials.
AB  - Cancer is the second leading cause of death worldwide and the morbidity is
      growing in developed countries. According to WHO, >14 million people per year are
      diagnosed with cancer and about 8 million die. Anti-cancer strategy includes
      chemo-, immune- and radiotherapy or their combination. Unfortunately, these
      widely used strategies often have insufficient efficacy and significant toxic
      effects on healthy cells. Consequently, the improvement of treatment approaches
      is an important goal. One of promising schemes to enhance the effect of therapy
      is the restriction of calorie intake or some nutrients. The combination of
      caloric restriction or its chemical mimetics along with anti-cancer drugs may
      suppress growth of tumor cells and enhance death of cancer cells. That will allow
      the dose of therapeutic drugs to be decreased and their toxic effects to be
      reduced. Here the possibility of using this combinatory therapy as well as the
      molecular mechanisms underlying this approach will be discussed.

PMID- 27871965
TI  - Molecular interplay between mutant p53 proteins and autophagy in cancer cells.
AB  - An increasing number of studies highlight the role of mutant p53 proteins in
      cancer cell growth and in the worsening of cancer patients' clinical outcome.
      Autophagy has been widely recognized as a main biological event involved in both
      the regulation of cancer cell proliferation and in the response of several
      anticancer drugs. A thorough analysis of scientific literature underlines the
      reciprocal interplay between mutant p53 proteins and autophagy regulation. In
      this review, we analytically summarize recent findings, which indicate that gain
      of-function (GOF) mutant p53 proteins counteract the autophagic machinery by
      various molecular mechanisms including the regulation of AMPK and Akt/mTOR
      pathways, autophagy-related genes (ATGs), HIF-1alpha target genes, and the
      mitochondrial citrate carrier CIC. Moreover, we report that mutant p53 protein
      stability is affected by lysosome-mediated degradation through macroautophagy or
      chaperone-mediated autophagy, suggesting the use of autophagy stimulators to
      counteract mutant p53 oncogenic activity. Finally, we discuss the functional role
      of the interplay between mutant p53 proteins and autophagy in cancer progression,
      a fundamental knowledge to design more effective therapies against cancers
      bearing mutant TP53 gene.

PMID- 27871966
TI  - Improvement in Compensation for Chronic Poststroke Homonymous Hemianopsia After
      Initiation of a Selective Serotonin Reuptake Inhibitor: A Case Report.
AB  - : Homonymous hemianopsia (HH) is a common adverse outcome after stroke.
      Spontaneous improvement more than 6 months poststroke is thought to be unlikely,
      and traditional visual rehabilitation techniques lack clear evidence of efficacy.
      The case presented is of a 22-year-old woman who demonstrated improved
      compensation of her stroke-induced HH after the initiation of a selective
      serotonin reuptake inhibitor (SSRI). There is evidence supporting the use of
      SSRIs to improve poststroke cognitive impairment, motor impairment, and
      depression. This is the first case, however, demonstrating the potential novel
      use SSRIs to improve HH compensation after stroke, to our knowledge. LEVEL OF
      EVIDENCE: V.

PMID- 27871967
TI  - Prevalence and Etiology of Hypogonadism in Young Men With Chronic Spinal Cord
      Injury: A Cross-Sectional Analysis From Two University-Based Rehabilitation
      Centers.
AB  - BACKGROUND: Spinal cord injury (SCI) triggers an "accelerated aging" process that
      may include development of hypogonadism, even among younger men with SCI;
      however, few studies have investigated the prevalence or etiology of hypogonadism
      in men with SCI. Young men with SCI also are at increased risk for developing
      metabolic dysfunction after injury, which may be exacerbated by concomitant
      testosterone (T) deficiency, thus identifying the prevalence and risk factors for
      T deficiency in men with SCI is important for their long-term health. OBJECTIVE:
      To investigate the prevalence, risk factors, and etiology of T deficiency
      (hypogonadism) in otherwise-healthy men with chronic, motor complete SCI. DESIGN:
      Secondary cross-sectional analysis. SETTING: Rehabilitation research centers in
      Washington, DC, and Miami, Florida. PARTICIPANTS: Men (n = 58) aged 18-45 years
      with chronic (>=1 year), motor complete SCI without comorbidities or use of
      testosterone therapy. METHODS: Plasma concentrations of hormones were measured
      with standardized assays. Body composition was assessed with dual-energy x-ray
      absorptiometry scan. MAIN OUTCOME MEASUREMENTS: Serum total T and calculated free
      T. RESULTS: T deficiency was more common in men after SCI than in a matched
      cohort of similarly-aged men without SCI (25%, SCI versus 6.7%, non-SCI, P <
      .001). The risk of hypogonadism appeared to be increased in men with more
      extensive injury and with higher percent body fat. The majority of men with SCI
      with low T had low serum LH levels, suggesting that central suppression of the
      hypothalamic-pituitary-gonadal axis may be the most common etiology of
      hypogonadism after SCI. CONCLUSIONS: Hypogonadism is more common in young men
      with SCI than in similarly aged men without SCI, suggesting that SCI should be
      identified as a risk factor for T deficiency and that routine screening for
      hypogonadism should be performed in the SCI population. LEVEL OF EVIDENCE: II.

PMID- 27871968
TI  - Lateral ligament reconstruction procedures for the ankle.
AB  - Capsule/ligament lesions of the lateral compartment of the ankle lead to lateral
      laxity, which is a prime contributor to chronic ankle instability. Lateral
      ligament reconstruction stabilizes the joint. Exhaustive preoperative clinical
      and paraclinical work-up is essential. The present article classifies, presents
      and criticizes the main techniques in terms of long-term stabilization and
      reduction of osteoarthritis risk. Anatomic ligament repair with reinforcement
      (mainly extensor retinaculum) or anatomic ligament reconstruction are the two
      recommended options. Non-anatomic reconstructions using the peroneus brevis
      should be abandoned. Arthroscopy is increasingly being developed, but results
      need assessment on longer follow-up than presently available. Postoperative
      neuromuscular reprogramming is fundamental to optimal recovery. Finally, the
      concept of complex ankle instability is discussed from the diagnostic and
      therapeutic points of view. The various forms of ligament reconstruction failure
      and corresponding treatments are reported.

PMID- 27871969
TI  - Oxidized zirconium on ceramic; Catastrophic coupling.
AB  - Oxidized zirconium (OxiniumTM; Smith & Nephew, Memphis, TN, USA) articulated with
      polyethylene in total hip arthroplasty (THA) appeared to have the potential to
      reduce wear dramatically. The thermally oxidized metal zirconium surface is
      transformed into ceramic-like hard surface that is resistant to abrasion. The
      exposure of soft zirconium metal under hard coverage surface after the damage of
      oxidized zirconium femoral head has been described. It occurred following joint
      dislocation or in situ succeeding disengagement of polyethylene liner. We
      reported three cases of misuse of OxiniumTM (Smith & Nephew, Memphis, TN, USA)
      heads. These three cases resulted in catastrophic in situ wear and inevitable
      failure although there was no advice, indication or recommendation for this use
      from the manufacturer.

PMID- 27871970
TI  - Surgical management of post-traumatic atlantoaxial rotatory fixation due to C2
      facet fracture: 5 clinical cases.
AB  - PURPOSE: Report the results of surgical treatment of post-traumatic atlantoaxial
      rotatory fixation (AARF) due to C2 articular facet fracture in adults. MATERIAL
      AND METHODS: The records of five patients treated since 2009 for AARF due to a C2
      articular facet fracture were analyzed retrospectively. Three women and two men
      with an average age of 60 years (27-82) were included, one of whom initially had
      neurological deficits. In all cases, the surgical strategy consisted of posterior
      fixation: Harms-type in four cases and trans-articular with hooks in one case.
      RESULTS: Dislocations due to fracture of the C2 articular facet are rare in
      adults; various treatment strategies have been described. In our experience,
      posterior screw fixation leads to satisfactory clinical and radiological
      outcomes. Fusion is not necessary in these cases because the dislocation is
      related to an asymmetric fracture without ligament damage. CONCLUSION: Posterior
      fixation provides satisfactory reduction of these injuries and leads to
      satisfactory bone union. This surgical treatment can be performed early on after
      the trauma and is an interesting alternative to conservative treatment.

PMID- 27871971
TI  - Speed-Bridge arthroscopic reinsertion of tibial eminence fracture (complementary
      to the adjustable button fixation technique).
AB  - In comminuted fractures of the intercondyloid eminence of the tibial spine, the
      quality of the reduction and the arthroscopic fixation, notably adjustable suture
      button fixation, is sometimes disappointing with reduction defects of the
      anterior bone block. In the Speed-Bridge technique, the two traction sutures of
      the adjustable button fixation are replaced with two braided sutures of different
      colors. After the button is placed above the eminence, reduction is obtained by
      tightening the loop of the button. The accessory communitive fragments are then
      packed in the depression around the main fragment. A second row provides bone
      suturing for these accessory fragments; traction sutures of the button are
      attached anteromedially and laterally with knotless anchors to obtain a Speed
      Bridge-type inverted-V bone suture. The Speed-Bridge arthroscopic reinsertion
      technique of the tibial eminence effectively completes the adjustable button bone
      suture technique for communitive fractures to obtain better reduction and good
      stability.

PMID- 27871972
TI  - Recombinant antibody fragment production.
AB  - Recombinant antibodies are now very important in both therapeutics and
      diagnostics and offer significant advantages over conventional antibodies. The
      generation of a single-chain variable antibody fragment (scFv) (a common and
      important recombinant antibody format) is used to demonstrate the construction of
      a recombinant antibody library. An immunotube-based two-day panning approach,
      using Escherichia coli as an expression system, is utilised for antibody
      screening. The methods used for antibody selection and purification using
      immobilised metal affinity chromatography (IMAC) are described.

PMID- 27871974
TI  - Anti-inflammatory sesquiterpene lactones from Onopordum illyricum L.
      (Asteraceae), an Italian medicinal plant.
AB  - Onopordum illyricum L. is a medicinal plant used in the Mediterranean area as
      antipyretic for the treatment of respiratory and urinary inflammations and to
      treat skin ulcers. Repeated chromatographic purification of O. illyricum aerial
      parts led to the isolation of six known sesquiterpenes, which were evaluated for
      the inhibition of the pro-inflammatory transcription factors NF-kappaB and STAT3
      and for the activation of the transcription factor Nrf2, which regulates the
      cellular antioxidant response. Structure-activity relationships were interpreted
      by the NMR-based cysteamine assay. The sesquiterpene lactone vernomelitensin
      significantly inhibited NF-kappaB and STAT3, showing also a significant Nrf2
      activation. Accordingly, the cysteamine assay selected vernomelitensin as the
      most reactive of the isolated sesquiterpenes, identifying the alpha,beta
      unsaturated aldehyde moiety as responsible for the higher (re)activity.

PMID- 27871973
TI  - PAR-CLIP and streamlined small RNA cDNA library preparation protocol for the
      identification of RNA binding protein target sites.
AB  - The study of protein-RNA interactions is critical for our understanding of
      cellular processes and regulatory circuits controlled by RNA binding proteins
      (RBPs). Recent next generation sequencing-based approaches significantly promoted
      our understanding of RNA biology and its importance for cell function. We present
      a streamlined protocol for Photoactivatable-Ribonucleoside-Enhanced Crosslinking
      and Immunoprecipitation (PAR-CLIP), a technique that allows for the
      characterization of RBP binding sites on target RNAs at nucleotide resolution and
      transcriptome-wide scale. PAR-CLIP involves irreversible UV-mediated crosslinking
      of RNAs labeled with photoreactive nucleosides to interacting proteins, followed
      by stringent purification steps and the conversion of crosslinked RNA into small
      RNA cDNA libraries compatible with next-generation sequencing. The defining
      hallmark of PAR-CLIP is a diagnostic mutation at the crosslinking site that is
      introduced into cDNA during the library preparation process. This feature allows
      for efficient computational removal of contaminating sequences derived from non
      crosslinked fragments of abundant cellular RNAs. In the following, we present two
      different step-by-step procedures for PAR-CLIP, which differ in the small RNA
      cDNA library preparation procedure: (1) Standard library preparation involving
      gel size selections after each enzymatic manipulation, and (2) A modified PAR
      CLIP procedure ("on-beads" PAR-CLIP), where most RNA manipulations including the
      necessary adapter ligation steps are performed on the immobilized RNP. This
      streamlined procedure reduces the protocol preparation time by three days
      compared to the standard workflow.

PMID- 27871975
TI  - The role of the Drosophila lateral horn in olfactory information processing and
      behavioral response.
AB  - Animals must rapidly and accurately process environmental information to produce
      the correct behavioral responses. Reactions to previously encountered as well as
      to novel but biologically important stimuli are equally important, and one
      understudied region in the insect brain plays a role in processing both types of
      stimuli. The lateral horn is a higher order processing center that mainly
      processes olfactory information and is linked via olfactory projection neurons to
      another higher order learning center, the mushroom body. This review focuses on
      the lateral horn of Drosophila where most functional studies have been performed.
      We discuss connectivity between the primary olfactory center, the antennal lobe,
      and the lateral horn and mushroom body. We also present evidence for the lateral
      horn playing roles in innate behavioral responses by encoding biological valence
      to novel odor cues and in learned responses to previously encountered odors by
      modulating neural activity within the mushroom body. We describe how these
      processes contribute to acceptance or avoidance of appropriate or inappropriate
      mates and food, as well as the identification of predators. The lateral horn is a
      sexually dimorphic and plastic region of the brain that modulates other regions
      of the brain to ensure that insects produce rapid and effective behavioral
      responses to both novel and learned stimuli, yet multiple gaps exist in our
      knowledge of this important center. We anticipate that future studies on
      olfactory processing, learning, and innate behavioral responses will include the
      lateral horn in their examinations, leading to a more comprehensive understanding
      of olfactory information relay and resulting behaviors.

PMID- 27871976
TI  - Developmental and reproductive responses of the spruce budworm (Lepidoptera:
      Tortricidae) parasitoid Tranosema rostrale (Hymenoptera: Ichneumonidae) to
      temperature.
AB  - The temperature-dependent development and survival of immatures, as well as adult
      longevity and potential fecundity of the endoparasitoid Tranosema rostrale
      (Hymenoptera: Ichneumonidae) parasitizing spruce budworm Choristoneura fumiferana
      (Lepidoptera: Tortricidae) larvae was investigated under laboratory conditions at
      several constant temperatures ranging from 5 to 30 degrees C. Maximum likelihood
      modeling approaches were used to estimate thermal responses in development,
      survival, and longevity. A model describing the effect of temperature on
      potential fecundity of the parasitoid was also developed taking oogenesis and
      oosorption into account. In-host and pupal development rates of the parasitoid
      increased with temperature up to 25 degrees C, and decreased thereafter. Immature
      survival was highest below 20 degrees C, and rapidly decreased at higher
      temperatures. Adult longevity decreased exponentially with increasing temperature
      for both males and females. Highest potential fecundity was reached at 10 degrees
      C. Considering survival and potential fecundity, the parasitoid seems best
      adapted to cool temperatures below 20 degrees C. Simulations of the life-history
      traits under variable temperature regimes indicate that temperature fluctuations
      decrease survival and increase realised fecundity compared to constant
      temperatures. The temperature-dependent fecundity model developed can be applied
      to other non-host-feeding synovigenic parasitoids. The equations and parameter
      estimates provided in this paper can be used to build comprehensive models
      predicting the seasonal phenology of this parasitoid and spruce budworm
      parasitism under changing climatic conditions.

PMID- 27871977
TI  - A time-course regulatory and kinetic expression study of steroid metabolizing
      enzymes by calcitriol in primary cultured human placental cells.
AB  - 1,25-dihydroxivitamin D3 (calcitriol), is a secoesteroid involved in several
      placental functions. In particular, we and others showed that calcitriol
      regulates peptides, proteins, cytokines and hormones production in human
      trophoblastic cells. On the other hand, calcitriol modifies the activity and
      expression of some steroidogenic enzymes, a process that is considered tissue
      specific. However, the effects of calcitriol on the expression of enzymes
      involved in the synthesis of sex steroids in placental tissue have not yet been
      entirely studied. The aim of the present study was to investigate the effects of
      calcitriol upon gene expression of several steroid enzymes such as cytochrome
      P450scc (CYP11A1), type 1 3beta-hydroxysteroid dehydrogenase(3beta-HSDI), 17beta
      HSD3, 17alpha-hydroxylase/17,20 lyase (CYP17A1) and aromatase (CYP19A1) in
      primary cultures of human placental cells. Cell cultures were performed using
      placentas obtained immediately after delivery by caesarean section from
      normotensive healthy women and calcitriol effects were evaluated, at level of
      transcription, by qPCR. The results showed that: 1) from basal expression values
      of the five genes studied, 3beta-HSDI was the most expressed gene (P<0.05); 2)
      basal expression of all enzymes was significantly higher in cultured
      syncytiotrophoblast than in cytotrophoblasts (P<0.05); 3) the presence of
      calcitriol in cultured trophoblast cells generally resulted in a stimulatory
      effect of CYP11A1, CYP19A1 and 17beta-HSD3 gene expression at 3h of treatment
      whereas 3beta-HSDI was induced at 6h (P<0.05). However, a time-dependent variable
      was also observed; 4) protein expression of CYP11A1 and 3beta-HSDI were not
      modified significantly by calcitriol, however that of CYP19A1 was regulated in
      similar fashion as gene expression. In conclusion, calcitriol affected in a time
      dependent manner the expression of steroids metabolizing enzymes in human
      placental cell cultures.

PMID- 27871979
TI  - Sex-specific effects of dehydroepiandrosterone (DHEA) on glucose metabolism in
      the CNS.
AB  - DHEA is a neuroactive steroid, due to its modulatory actions on the central
      nervous system (CNS). DHEA is able to regulate neurogenesis, neurotransmitter
      receptors and neuronal excitability, function, survival and metabolism. The
      levels of DHEA decrease gradually with advancing age, and this decline has been
      associated with age related neuronal dysfunction and degeneration, suggesting a
      neuroprotective effect of endogenous DHEA. There are significant sex differences
      in the pathophysiology, epidemiology and clinical manifestations of many
      neurological diseases. The aim of this study was to determine whether DHEA can
      alter glucose metabolism in different structures of the CNS from male and female
      rats, and if this effect is sex-specific. The results showed that DHEA decreased
      glucose uptake in some structures (cerebral cortex and olfactory bulb) in males,
      but did not affect glucose uptake in females. When compared, glucose uptake in
      males was higher than females. DHEA enhanced the glucose oxidation in both males
      (cerebral cortex, olfactory bulb, hippocampus and hypothalamus) and females
      (cerebral cortex and olfactory bulb), in a sex-dependent manner. In males, DHEA
      did not affect synthesis of glycogen, however, glycogen content was increased in
      the cerebral cortex and olfactory bulb. DHEA modulates glucose metabolism in a
      tissue-, dose- and sex-dependent manner to increase glucose oxidation, which
      could explain the previously described neuroprotective role of this hormone in
      some neurodegenerative diseases.

PMID- 27871978
TI  - Differences in testosterone and its precursors by sex of the offspring in
      meconium.
AB  - Prenatal metabolism exerts profound effects on development. The first stool of
      the newborn, meconium, provides a window into the prenatal metabolic environment.
      The objective of this study was to examine the feasibility of meconium as a novel
      matrix to quantify prenatal steroid levels. We quantified parameters of
      analytical interest regarding the use of meconium, including sample stability. We
      hypothesized that meconium steroid content would differ by sex, prompting
      analysis of meconium to test effects of prenatal steroid metabolism. Meconium
      from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation
      (EARLI) study, including 107 males, and 86 females, were analyzed by isotope
      dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS)
      while blinded to identity for testosterone (T), androstenedione (AD), and
      dehydroepiandrosterone (DHEA). Steroid levels were compared by sex, and
      investigations of potential trends resulting from sample storage or processing
      was conducted. The unconjugated steroid content of meconium in ng/g (mean,
      standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA
      (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06,
      43.49). T was higher in meconium from males (p=0.0333), and DHEA was higher in
      meconium from females (p=0.0202). 6 female and 3 male T values were below the
      limit of detection. No extreme variability in hydration or trend in steroid
      levels by storage time was detected. Sexually dimorphic levels of hormones may
      reflect gestational differentiation, and future studies should consider meconium
      analysis.

PMID- 27871981
TI  - Oral exposure to diisodecyl phthalate aggravates allergic dermatitis by oxidative
      stress and enhancement of thymic stromal lymphopoietin.
AB  - Diisodecyl phthalate (DIDP) is extensively used as an environmentally friendly
      plasticizer. However, little is known about the adverse effects and the
      underlying mechanisms of DIDP exposure on immunological diseases. We aimed to
      determine the role and mechanisms of DIDP exposure in allergic contact dermatitis
      like skin lesions. We show that oral DIDP exposure can aggravate allergic
      dermatitis in mice. Moreover, an increase of ROS, total serum IgE and IL-4 levels
      were concomitant with this deterioration. We detected the expression of Thymic
      stromal lymphopoietin (TSLP) and the activation of STATs and NF-kappaB signal
      pathways. The data indicated that DIDP in combination with FITC triggers TSLP
      production. Our results also suggested that DIDP exacerbated the activation of NF
      kappaB signal pathways, with an enhancement in TSLP expression, which potentiated
      the activation of STATs and the degranulation of mast cells in the skin, and
      finally exacerbated allergic dermatitis. The study also suggested that melatonin
      enhanced the expression of Nrf2, up-regulated the antioxidant genes HO-1 and
      NQO1, reduced the levels of oxidative stress and TSLP, and alleviated allergic
      dermatitis. The results demonstrated that DIDP exacerbated allergic dermatitis
      through oxidative stress and enhanced TSLP production.

PMID- 27871980
TI  - Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a
      2-year gavage study.
AB  - Furan is a volatile organic chemical that is a contaminant in many common foods.
      Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from
      dietary exposure to furan cannot be estimated accurately because the lowest
      tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of
      cholangiocarcinoma. To provide bioassay data that can be used in preparing risk
      assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats
      administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body
      weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated
      with the development of malignant mesothelioma on membranes surrounding the
      epididymis and on the testicular tunics, with the increase being significant at 2
      mg furan/kg BW. There was also a dose-related increase in the incidence of
      mononuclear cell leukemia, with the increase in incidence being significant at
      0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions
      included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract
      hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic
      vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis,
      the frequency of which increased significantly at 0.2 mg furan/kg BW.

PMID- 27871982
TI  - Filipendula ulmaria extracts attenuate cisplatin-induced liver and kidney
      oxidative stress in rats: In vivo investigation and LC-MS analysis.
AB  - Filipendula ulmaria, known as meadowsweet, is a perennial herb found in wild and
      cultivated habitats in Europe and Asia. Usage of F. ulmaria in traditional
      medicine is based on diuretic, astringent, antirheumatic, and anti-inflammatory
      properties of this plant. Exposure to cisplatin at a dose of 7.5 mg/kg caused
      significant increase in serum parameters of liver and kidneys function and tissue
      oxidative stress markers along with some histopathological changes in liver and
      kidney tissues of experimental rats, as well as high level of genotoxicity.
      Administration of F. ulmaria extracts in three different concentrations (100,
      200, and 400 mg/kg/day) for 10 days resulted in a reduction of oxidative stress
      in tissues and decrease of serum parameters. Moreover, tested extracts attenuated
      the genotoxicity of cisplatin in reverse dose-dependent manner. F. ulmaria
      extracts had no in vitro cytotoxic activity at all applied concentrations (IC50 >
      50 MUg/mL). Tested extracts, rich in polyphenolic compounds, attenuate cisplatin
      induced liver and kidney oxidative stress, reduce tissue damage, and enhance the
      antioxidative status of experimental animals during cisplatin application.
      Therefore, F. ulmaria extracts may be used as supportive agent for the prevention
      and amelioration of cisplatin side effects.

PMID- 27871983
TI  - Safer, but not perfect.

PMID- 27871984
TI  - Reply to the Editor- Anticoagulation in atrial fibrillation after intracranial
      hemorrhage: could the hemorrhage location influence the outcome?

PMID- 27871985
TI  - To the Editor- Anticoagulation in atrial fibrillation after intracranial
      hemorrhage: Could the hemorrhage location influence the outcome?

PMID- 27871986
TI  - Second-generation cryoballoon ablation without the use of real-time recordings: A
      novel strategy based on a temperature-guided approach to ablation.
AB  - BACKGROUND: The achievement of -40 degrees C within the first 60 seconds during
      cryoenergy applications has proven to independently predict durable pulmonary
      vein (PV) isolation in the setting of second-generation cryoballoon (CB-A;
      Medtronic, Minneapolis, MN) ablation. OBJECTIVE: We sought to evaluate a strategy
      based on the attainment of the specific parameter of -40 degrees C within the
      first 60 seconds during cryoenergy applications in the setting of CB-A ablation
      without the use of an inner lumen mapping catheter (Achieve, Medtronic) for the
      visualization of real-time recordings. METHODS: A total of 52 patients having
      undergone CB ablation for paroxysmal atrial fibrillation (AF) between 1 February
      2015 and 30 June 2015 who underwent a temperature-guided approach based on
      achieving -40 degrees C within 60 seconds without real-time recordings (wire
      group) were compared with a cohort of 52 propensity score-matched patients having
      undergone CB ablation performed with an inner lumen mapping catheter (Achieve
      group). All PVs were checked for electrical isolation at the end of the procedure
      with a circular mapping catheter in the wire group. RESULTS: Electrical isolation
      could be obtained in all patients in the Achieve group and in 99% of PVs in the
      wire group. Freedom from AF without antiarrhythmic drugs at a mean follow-up of
      12.4 +/- 3.0 months did not significantly differ between both groups (85% vs 88%,
      respectively; P = .56). CONCLUSION: A temperature-guided approach based on
      achieving -40 degrees C within 60 seconds is effective in producing PV isolation
      and affords freedom from AF at 12-month follow-up in 85% of patients affected by
      paroxysmal AF after a 3-month blanking period.

PMID- 27871987
TI  - Body surface mapping using an ECG belt to characterize electrical heterogeneity
      for different left ventricular pacing sites during cardiac resynchronization:
      Relationship with acute hemodynamic improvement.
AB  - BACKGROUND: Electrical heterogeneity (EH) during cardiac resynchronization
      therapy may vary with different left ventricular (LV) pacing sites. OBJECTIVE:
      The purpose of this study was to evaluate the relationship between such changes
      and acute hemodynamic response (AHR). METHODS: Two EH metrics-standard deviation
      of activation times and mean left thorax activation times-were computed from
      isochronal maps based on 53-electrode body surface mapping during baseline AAI
      pacing and biventricular (BiV) pacing from different pacing sites in coronary
      veins in 40 cardiac resynchronization therapy-indicated patients. AHR at
      different sites was evaluated by invasive measurement of LV-dp/dtmax at baseline
      and BiV pacing, along with right ventricular (RV)-LV sensing delays and QRS
      duration. RESULTS: The site with the greatest combined reduction in standard
      deviation of activation times and left thorax activation times from baseline to
      BiV pacing was hemodynamically optimal (defined by AHR equal to, or within 5% of,
      the largest dp/dt response) in 35 of 40 patients (88%). Sites with the longest RV
      LV and narrowest paced QRS were hemodynamically optimal in 26 of 40 patients
      (65%) and 28 of 40 patients (70%), respectively. EH metrics from isochronal maps
      had much better accuracy (sensitivity 90%, specificity 80%) for identifying
      hemodynamically responsive sites (?LV dp/dtmax >=10%) compared with RV-LV delay
      (69%, 85%) or paced QRS reduction (52%, 76%). Multivariate prediction model based
      on EH metrics showed significant correlation (R2 = 0.53, P <.001) between
      predicted and measured AHR. CONCLUSION: Changes in EH from baseline to BiV pacing
      more accurately identified hemodynamically optimal sites than RV-LV delays or
      paced QRS shortening. Optimization of LV lead location by minimizing EH during
      BiV pacing, based on body surface mapping, may improve CRT response.

PMID- 27871989
TI  - Quality by design (QbD) approach of pharmacogenomics in drug designing and
      formulation development for optimization of drug delivery systems.
AB  - Conventional approaches of drug discovery are very complex, costly and time
      consuming. But after the completion of human genome project, applications of
      pharmacogenomics in this area completely revolutionize the drug discovery and
      development process to produce a quality by design (QbD) approach based products.
      The applications of two areas of pharmacogenomics i.e. structural and functional
      pharmacogenomics excel the drug discovery process by employing genomic data in
      drug target identification and evaluation, lead optimization via high throughput
      screening, evaluation of drug metabolizing enzymes, drug transporters and drug
      receptors using computer aided technique and bioinformatics library data base.
      Pharmacogenomics also provides an important and reliable basis for evaluation and
      optimization of the dosage forms as well as repositioning of failed drugs for the
      treatment of new disease. Various dosage forms of category of drugs such as
      anticancer drugs, vaccines, gene and DNA delivery systems and immunological
      agents can be easily evaluated based on the genetic markers of the related
      disease. The effect of different formulation polymers on pharmacokinetic and
      pharmacodynamic properties of drugs can be assessed easily and therefore it plays
      an important role in formulation optimization. However, current applications of
      pharmacogenomics in drug discovery and formulation optimization are very limited
      because of costly and non accessible techniques for everyone, but in future, with
      the advancement in the technology; the application of genomic data in drug
      discovery will provide us with innovative, safer and more efficacious medicines.

PMID- 27871988
TI  - Sonoporation with Acoustic Cluster Therapy (ACT(r)) induces transient tumour
      volume reduction in a subcutaneous xenograft model of pancreatic ductal
      adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with
      survival averaging only 3months if untreated following diagnosis. A major
      limitation in effectively treating PDAC using conventional and targeted
      chemotherapeutic agents, is inadequate drug delivery to the target location,
      predominantly due to a poorly vascularised, desmoplastic tumour microenvironment.
      Ultrasound in combination with ultrasound contrast agents, i.e., microbubbles,
      that flow through the vasculature and capillaries can be used to disrupt such
      mechanical barriers, potentially allowing for a greater therapeutic efficacy.
      This phenomenon is commonly referred to as sonoporation. In an attempt to improve
      the efficacy of sonoporation, novel microbubble formulations are being developed
      to address the limitation of commercially produced clinical diagnostic ultrasound
      contrast agents. In our work here we evaluate the ability of a novel formulation;
      namely Acoustic Cluster Therapy (ACT(r)) to improve the therapeutic efficacy of
      the chemotherapeutic agent paclitaxel, longitudinally in a xenograft model of
      PDAC. Results indicated that ACT(r) bubbles alone demonstrated no observable
      toxic effects, whilst ACT(r) in combination with paclitaxel can transiently
      reduce tumour volumes significantly, three days posttreatment (p=0.0347-0.0458).
      Quantitative 3D ultrasound validated the calliper measurements. Power Doppler
      ultrasound imaging indicated that ACT(r) in combination with paclitaxel was able
      to transiently sustain peak vasculature percentages as observed in the initial
      stages of tumour development. Nevertheless, there was no significant difference
      in tumour vasculature percentage at the end of treatment. The high vascular
      percentage correlated to the transient decrease and overall inhibition of the
      tumour volumes. In conclusion, ACT(r) improves the therapeutic efficacy of
      paclitaxel in a PDAC xenograft model allowing for transient tumour volume
      reduction and sustained tumour vasculature percentage.

PMID- 27871990
TI  - Multifunctional gold-nanoparticles: A nanovectorization tool for the targeted
      delivery of novel chemotherapeutic agents.
AB  - Due to their small size and unique properties, multifunctional nanoparticles
      arise as versatile delivery systems easily grafted with a vast array of
      functional moieties, such as anticancer cytotoxic chemotherapeutics and targeting
      agents. Here, we formulated a multifunctional gold-nanoparticle (AuNP) system
      composed of a monoclonal antibody against epidermal growth factor receptor (EGFR)
      (anti-EGFR D-11) for active targeting and a Co(II) coordination compound
      [CoCl(H2O)(phendione)2][BF4] (phendione=1,10-phenanthroline-5,6-dione) (TS265)
      with proven antiproliferative activity towards cancer cells (designated as
      TargetNanoTS265). The efficacy of this nanoformulation, and the non-targeted
      counterpart (NanoTS265), were evaluated in vitro using cancer cell models and in
      vivo using mice xenografts. Compared to the free compound, both nanoformulations
      (TargetNanoTS265 and NanoTS265) efficiently delivered the cytotoxic cargo in a
      controlled selective manner due to the active targeting, boosting tumor
      cytotoxicity. Treatment of HCT116-derived xenografts tumors with TargetNanoTS265
      led to 93% tumor reduction. This simple conceptual nanoformulation demonstrates
      the potential of nanovectorization of chemotherapeutics via simple assembly onto
      AuNPs of BSA/HAS-drug conjugates that may easily be expanded to suit other cargo
      of novel compounds that require optimized controlled delivery to cancer target.

PMID- 27871992
TI  - To exploit the tumor microenvironment: Since the EPR effect fails in the clinic,
      what is the future of nanomedicine?
AB  - Tumor targeting by nanomedicine-based therapeutics has emerged as a promising
      approach to overcome the lack of specificity of conventional chemotherapeutic
      agents and to provide clinicians the ability to overcome shortcomings of current
      cancer treatment. The major underlying mechanism of the design of nanomedicines
      was the Enhanced Permeability and Retention (EPR) effect, considered as the
      "royal gate" in the drug delivery field. However, after the publication of
      thousands of research papers, the verdict has been handed down: the EPR effect
      works in rodents but not in humans! Thus the basic rationale of the design and
      development of nanomedicines in cancer therapy is failing making it necessary to
      stop claiming efficacy gains via the EPR effect, while tumor targeting cannot be
      proved in the clinic. It is probably time to dethrone the EPR effect and to ask
      the question: what is the future of nanomedicines without the EPR effect? The aim
      of this review is to provide a general overview on (i) the current state of the
      EPR effect, (ii) the future of nanomedicine and (iii) the strategies of
      modulation of the tumor microenvironment to improve the delivery of nanomedicine.

PMID- 27871991
TI  - Tumor-targeted micelle-forming block copolymers for overcoming of multidrug
      resistance.
AB  - New amphiphilic diblock polymer nanotherapeutics serving simultaneously as a drug
      delivery system and an inhibitor of multidrug resistance were designed,
      synthesized, and evaluated for their physico-chemical and biological
      characteristics. The amphiphilic character of the diblock polymer, containing a
      hydrophilic block based on the N-(2-hydroxypropyl)methacrylamide copolymer and a
      hydrophobic poly(propylene oxide) block (PPO), caused self-assembly into polymer
      micelles with an increased hydrodynamic radius (Rh of approximately 15nm) in
      aqueous solutions. Doxorubicin (Dox), as a cytostatic drug, was bound to the
      diblock polymer through a pH-sensitive hydrazone bond, enabling prolonged
      circulation in blood, the delivery of Dox into a solid tumor and the subsequent
      stimuli-sensitive controlled release within the tumor mass and tumor cells at a
      decreased pH. The applicability of micellar nanotherapeutics as drug carriers was
      confirmed by an in vivo evaluation using EL4 lymphoma-bearing C57BL/6 mice. We
      observed significantly higher accumulation of micellar conjugates in a solid
      tumor because of the EPR effect compared with similar polymer-drug conjugates
      that do not form micellar structures or with the parent free drug. In addition,
      highly increased anti-tumor efficacy of the micellar polymer nanotherapeutics,
      even at a sub-optimal dose, was observed. The presence of PPO in the structure of
      the diblock polymer ensured, during in vitro tests on human and mouse drug
      sensitive and resistant cancer cell lines, the inhibition of P-glycoprotein, one
      of the most frequently expressed ATP-dependent efflux pump that causes multidrug
      resistance. In addition, we observed highly increased rate of the uptake of the
      diblock polymer nanotherapeutics within the cells. We suppose that combination of
      unique properties based on MDR inhibition, stimuli sensitiveness (pH sensitive
      activation of drug), improved pharmacokinetics and increased uptake into the
      cells made the described polymer micelle a good candidate for investigation as
      potential drug delivery system.

PMID- 27871993
TI  - MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications
      for osteoarthritis treatment.
AB  - Mesenchymal stem cell (MSC) therapies have demonstrated efficacy in cartilage
      repair in animal and clinical studies. The efficacy of MSC-based therapies which
      was previously predicated on the chondrogenic potential of MSC is increasingly
      attributed to the paracrine secretion, particularly exosomes. Exosomes are
      thought to function primarily as intercellular communication vehicles to transfer
      bioactive lipids, nucleic acids (mRNAs and microRNAs) and proteins between cells
      to elicit biological responses in recipient cells. For MSC exosomes, many of
      these biological responses translated to a therapeutic outcome in injured or
      diseased cells. Here, we review the current understanding of MSC exosomes,
      discuss the possible mechanisms of action in cartilage repair within the context
      of the widely reported immunomodulatory and regenerative potency of MSC exosomes,
      and provide new perspectives for development of an off-the-shelf and cell-free
      MSC therapy for treatment of cartilage injuries and osteoarthritis.

PMID- 27871994
TI  - Root bark of Morus alba ameliorates the depressive-like behaviors in diabetic
      rats.
AB  - Diabetes-induced depression is one of the severe chronic complications of
      diabetes mellitus. Up to now, there are only a few effective medicines to prevent
      or manage the co-morbidity of diabetes and depression. The present study was to
      investigate the effect of root bark of Morus alba (RBM) on depressive-like
      behaviors in the diabetic rats established by a high fat diet and a low dose of
      streptozotocin. Depressive-like behaviors were measured by the open field test,
      locomotor activity test and forced swimming test. Plasma glucose and lipid
      parameters were also measured. Expression of Brain-derived neurotrophic factor
      (BDNF) and phosphorylation of extracellular signal-regulated kinase (ERK) and Akt
      in the prefrontal cortex (PFC) were assessed. The results showed that a 4-week
      administration of RBM (10g/kg, ig) significantly reversed the depressive-like
      behaviors. BDNF expression and phosphorylation of ERK and Akt were increased in
      the PFC following RBM treatment in the diabetic rats. The data demonstrated that
      RBM could improve the depressive-like behaviors induced by diabetes, suggesting a
      therapeutic potential of RBM for the diabetes-associated depression.

PMID- 27871996
TI  - The role of glucocorticoids in emotional memory reconsolidation.
AB  - Glucocorticoids are secreted following exposure to stressful events. Their
      modulating role on memory reconsolidation, a post-retrieval process of re
      stabilization, has been investigated only recently, at times with conflicting
      results. The goal of this review is twofold. First, to establish the modulating
      role of glucocorticoids on memory reconsolidation. Second, to point the potential
      factors and confounds that might explain the seemingly paradoxical findings. Here
      we review recent pharmacological studies, conducted in rodents and humans, which
      suggest a critical role of glucocorticoids in this post-retrieval process. In
      particular, the activation of glucocorticoid receptors in the amygdala and
      hippocampus is suggested to be involved in emotional memories reconsolidation,
      pointing to a similarity between post-retrieval reconsolidation and initial
      memory consolidation. In addition, based on the general reconsolidation
      literature, we suggest several factors that might play a role in determining the
      direction and strength of the reconsolidation effect following glucocorticoids
      treatment: memory-related factors, manipulation-related factors, and individual
      differences. We conclude that only when taking these additional factors into
      account can the paradox be resolved.

PMID- 27871995
TI  - Outbred CD1 mice are as suitable as inbred C57BL/6J mice in performing social
      tasks.
AB  - Inbred mouse strains have been used preferentially for behavioral testing over
      outbred counterparts, even though outbred mice reflect the genetic diversity in
      the human population better. Here, we compare the sociability of widely available
      outbred CD1 mice with the commonly used inbred C57BL/6J (C57) mice in the one
      chamber social interaction test and the three-chamber sociability test. In the
      one-chamber task, intra-strain pairs of juvenile, non-littermate, male CD1 or C57
      mice display a series of social and aggressive behaviors. While CD1 and C57 pairs
      spend equal amount of time socializing, CD1 pairs spend significantly more time
      engaged in aggressive behaviors than C57 mice. In the three-chamber task,
      sociability of C57 mice was less dependent on acclimation paradigms than CD1
      mice. Following acclimation to all three chambers, both groups of age-matched
      male mice spent more time in the chamber containing a stranger mouse than in the
      empty chamber, suggesting that CD1 mice are sociable like C57 mice. However, the
      observed power suggests that it is easier to achieve statistical significance
      with C57 than CD1 mice. Because the stranger mouse could be considered as a novel
      object, we assessed for a novelty effect by adding an object. CD1 mice spend more
      time in the chamber with a stranger mouse than that a novel object, suggesting
      that their preference is social in nature. Thus, outbred CD1 mice are as
      appropriate as inbred C57 mice for studying social behavior using either the
      single or the three-chamber test using a specific acclimation paradigm.

PMID- 27871997
TI  - Survival and prevalence of Clostridium difficile in manure compost derived from
      pigs.
AB  - Pigs, particularly piglets, have been identified as reservoir hosts of
      Clostridium difficile. To examine the survival ability of this pathogen in pig
      feces-based manure compost, C. difficile spores, which were prepared to contain
      as few vegetative cells as possible, were artificially inoculated into pig feces
      and incubated at different temperatures. While C. difficile survived in the feces
      incubated at temperatures below 37  degrees C for over 30 days, cell numbers
      gradually decreased at thermophilic temperatures (over 55  degrees C; p < 0.05).
      Next, to clarify the prevalence of C. difficile in field manure compost, we
      isolated and characterized C. difficile from the final products of manure compost
      products of 14 pig farms. A total of 11 C. difficile strains were isolated from 5
      of 14 (36% positive rate) samples tested. Of these 11 strains, 82% were
      toxigenic, with ribotype 078 being the most prevalent. Thus, the application of
      composted manure to land therefore poses a possible risk of C. difficile transfer
      to the food chain.

PMID- 27871999
TI  - What Happens in Vegas.

PMID- 27871998
TI  - Isolation of a sulfide-producing bacterial consortium from cooling-tower water:
      Evaluation of corrosive effects on galvanized steel.
AB  - Sulfidogenic Clostridia and sulfate reducing bacteria (SRB) often cohabit in
      nature. The presence of these microorganisms can cause microbially influenced
      corrosion (MIC) of materials in different ways. To investigate this aspect,
      bacteria were isolated from cooling tower water and used in corrosion tests of
      galvanized steel. The identity of the isolates was determined by comparative
      sequence analysis of PCR-amplified 16S rDNA gene fragments, separated by
      denaturing gradient gel electrophoresis (DGGE). This analysis showed that, in
      spite of the isolation process, colonies were not pure and consisted of a mixture
      of bacteria affiliated with Desulfosporosinus meridiei and Clostridium sp. To
      evaluate the corrosive effect, galvanized steel coupons were incubated with a
      mixed culture for 4, 8, 24, 72, 96, 168, 360 and 744 h, along with a control set
      in sterile culture medium only. The corrosion rate was determined by weight loss,
      and biofilm formation and corroded surfaces were observed by scanning electron
      microscopy (SEM). Although the sulfide-producing bacterial consortium led to a
      slight increase in the corrosion of galvanized steel coupons, when compared to
      the previous studies it can be said that Clostridium sp. can reduce the corrosive
      effect of the Desulfosporosinus sp. strain.

PMID- 27872001
TI  - Psychosocial Approaches for Sexual Health and Intimate Relationships Among
      Patients With Serious Mental Illness.
AB  - INTRODUCTION: The sexual health and behavior and the intimate relationships of
      patients diagnosed with a serious mental illness (SMI) have been described as
      ongoing and often ignored concerns in mental health treatment. Evidence-based
      psychosocial interventions have emerged as effective complimentary approaches to
      address symptoms of SMI in conjunction with psychopharmacology, yet rarely do
      they address sexual concerns in a targeted manner. AIM: This systematic review
      explores the scope and efficacy of psychosocial interventions designed to address
      sexual health and behavior and intimate relationship concerns in patients with
      SMI. METHODS: The search was conducted in four targeted databases and identified
      967 articles with four of those meeting inclusion criteria for this review. MAIN
      OUTCOME MEASURES: The data extracted included setting, study sample, study
      design, outcome measures, data analysis, and results. The measures utilized in
      the studies assess mental and sexual health-related outcomes. RESULTS: All four
      studies reported an improvement in sexual and mental health outcomes. CONCLUSION:
      Given the lack of psychosocial approaches and culturally sensitive adaptations,
      this review highlights a gap in literature that should be addressed, particularly
      emphasizing their combined treatment with psychotropic medication and efficacy
      testing with diverse populations.

PMID- 27872000
TI  - Is Testosterone a Food for the Brain?
AB  - INTRODUCTION: Testosterone is fundamental for psychological, sexological,
      cognitive, and reproductive aspects, and its lack or reduction largely impacts
      the quality of life in males and females. AIM: Therefore, the aim of this review
      is to describe the role of testosterone in the neurophysiology of the brain and
      related aspects regarding the quality of general and sexual life. METHODS: We
      listed and discussed the principal studies on the role of testosterone in the
      brain regarding sexual health, psychopathological conditions, and the elderly.
      The search strategies were composed by the insertion of specific terms in PubMed
      regarding the main studies from January 2000 to June 2015. MAIN OUTCOME MEASURES:
      Using a psychoneuroendocrinologic perspective, we considered 4 main sections:
      brain and testosterone, sexuality and testosterone, psychopathology and
      testosterone, and cognitive impairment and testosterone. RESULTS: Much evidence
      on the neuroendocrinology of testosterone regarding brain activity, sexual
      function, psychological health, and senescence was found. In any case, it is
      known that testosterone deficiency negatively impacts quality of life, first, but
      not exclusively, through a central effect. Moreover, testosterone and androgen
      receptors are differently expressed according to age and gender. This aspect
      contributes to gender differences and to the dimorphic physiological role of this
      hormone. CONCLUSION: A universal role for testosterone can be recognized: low
      levels of testosterone are associated with mental disorders, sexual dysfunction,
      and cognitive impairment in both sexes. Hence, physicians should carefully assess
      testosterone levels, not only in the management of sexual dysfunctions but also
      when seeking to help patients with severe mental or organic diseases.

PMID- 27872002
TI  - Gender Dysphoria and Autism Spectrum Disorder: A Systematic Review of the
      Literature.
AB  - INTRODUCTION: There is a growing clinical recognition that a significant
      proportion of patients with gender dysphoria have concurrent autism spectrum
      disorder (ASD). AIM: The purpose of this review is to systematically appraise the
      current literature regarding the co-occurrence of gender dysphoria and ASD.
      METHODS: A systematic literature search using Medline and PubMed, PsycINFO, and
      Embase was conducted from 1966 to July 2015. MAIN OUTCOME MEASURES: Fifty-eight
      articles were generated from the search. Nineteen of these publications met the
      inclusion criteria. RESULTS: The literature investigating ASD in children and
      adolescents with gender dysphoria showed a higher prevalence rate of ASD compared
      with the general population. There is a limited amount of research in adults.
      Only one study showed that adults attending services for gender dysphoria had
      increased ASD scores. Another study showed a larger proportion of adults with
      atypical gender identity and ASD. CONCLUSION: Although the research is limited,
      especially for adults, there is an increasing amount of evidence that suggests a
      co-occurrence between gender dysphoria and ASD. Further research is vital for
      educational and clinical purposes.

PMID- 27872003
TI  - Primary and Secondary Provoked Vestibulodynia: A Review of Overlapping and
      Distinct Factors.
AB  - INTRODUCTION: A common subtype of vulvodynia is provoked vestibulodynia (PVD),
      characterized by severe pain upon contact to the vaginal entrance. Some
      researchers have further delineated the PVD group based on pain onset (primary vs
      secondary PVD, referred to as PVD1 and PVD2, respectively). AIM: This study aims
      to review available evidence regarding sociodemographic variables, pain
      characteristics, medical history and examination findings, quantitative sensory
      testing, genetic markers, psychosocial/sexual/relationship function, treatment
      outcome, and brain imaging in women with PVD1 and PVD2. METHODS: All available
      data related to PVD1 and PVD2 were reviewed. MAIN OUTCOME MEASURES: There is
      mixed evidence supporting the assumption that women with PVD1 fare worse on all
      variables investigated. RESULTS: The review indicated that although women with
      PVD1 seem to fare worse on many variables examined (eg, pain severity, genetic
      markers), many studies also indicated no significant group differences or-less
      commonly-that women with PVD2 fare worse on some variables (eg, sexual function).
      CONCLUSION: Although it has been suggested that different pathophysiologic
      processes are involved in the development and maintenance of PVD1 and PVD2, the
      data reviewed were mixed. While most studies indicated that women with PVD1 have
      higher pain intensity, higher sensitivity, more genetic influence, more evidence
      of inflammation, lower successful treatment outcomes, and different neural
      activation patterns and structural findings, these results were not consistently
      reported. In addition, the data for subgroup differences in psychosocial, sexual,
      and relationship variables were not convincing. A more precise definition of
      primary and secondary PVD is needed, and importantly, prospective, longitudinal
      studies are essential for clarifying any differences within these PVD subgroups.

PMID- 27872004
TI  - HIV and Men.
AB  - INTRODUCTION: Since the initial description of HIV and AIDS, monumental efforts
      have been made both in the developed and developing countries to devise
      strategies and medications to control the disease. The advent of highly active
      antiretroviral therapy has now meant that the diagnosis of HIV is no longer a
      life-sentence and compliant patients with HIV can expect life expectancy similar
      to their noninfected peers. Consequently new challenges have arisen in the
      management of benign conditions. AIM: To provide an overview of the key
      conditions and issues that HIV/AIDS patients may present with to an andrological
      service. METHODS: Using PubMed, we screened the literature for studies on common
      andrological conditions specifically pertaining to HIV and AIDS. MAIN OUTCOME
      MEASURES: The urological manifestations of HIV/AIDS in men have been summarized
      in an attempt to provide a useful guide for sexual health practitioners dealing
      with HIV-positive men. RESULTS: As a result of advancements in pharmaceuticals,
      life expectancy of men infected with HIV has improved almost to that of the
      general population in developed countries. Therefore, clinicians are faced with
      non-life-threatening urological problems that affect the quality of life of men
      with HIV. The majority of these problems can be managed easily, by adapting a
      "patient-centered" approach, instead of "disease-centered" algorithms.
      CONCLUSION: With improved survival and understanding, patients with HIV/AIDS can
      and do expect to enjoy a healthy sex life. With appropriate counseling around
      safe sex and careful management with consideration for disease-specific issues as
      well as the influence of medical therapy, patients can achieve a good quality of
      life.

PMID- 27872005
TI  - The Role of Pelvic Floor Muscles in Male Sexual Dysfunction and Pelvic Pain.
AB  - INTRODUCTION: Sexual function is essential to good health and well-being in men.
      The relationship between male sexual function, pelvic floor function, and pelvic
      pain is complex and only beginning to be appreciated. AIM: The objectives of the
      current review are to examine these complex relationships, and to demonstrate how
      pelvic floor physical therapy can potentially improve the treatment of various
      male sexual dysfunctions, including erectile dysfunction and dysfunction of
      ejaculation and orgasm. METHODS: Contemporary data on pelvic floor anatomy and
      function as they relate to the treatment of various male sexual dysfunctions were
      reviewed. MAIN OUTCOME MEASURES: Examination of evidence supporting the
      association between the male pelvic floor and erectile dysfunction,
      ejaculatory/orgasmic dysfunction, and chronic prostatitis/chronic pelvic pain
      syndrome, respectively. RESULTS: Evidence suggests a close relationship between
      the pelvic floor and male sexual dysfunction and a potential therapeutic benefit
      from pelvic floor therapy for men who suffer from these conditions. CONCLUSION:
      Pelvic floor physical therapy is a necessary tool in a more comprehensive bio
      neuromusculoskeletal-psychosocial approach to the treatment of male sexual
      dysfunction and pelvic pain.

PMID- 27872006
TI  - Aging and Erectile Dysfunction.
AB  - INTRODUCTION: Erectile dysfunction (ED) has been identified as the most common
      sexual problem that affects mainly men older than 40 years. According to this,
      there is a strong evidence linking ED with a number of medical conditions and
      related risk factors that had been described in the literature, yet there is
      limited information about the specific mechanism involved in the establishment of
      ED among healthy older men. AIM: The purpose of this study is to review the
      literature and mainly focus on the basic physiologic and vascular alterations and
      morphologic changes related to aging and its related risk factors, summarizing
      the main and the latest findings in basic research of tissue remodeling process
      involved in ED pathophysiology. METHODS: Data from the pertinent literature were
      examined to inform our conclusions. MAIN OUTCOME MEASURE: This article defines
      the morphologic and physiologic mechanisms involved in the process of aging,
      which play a key role in the development of sexual dysfunction. RESULTS: ED has
      been considered as a nonlife-threatening condition, but the recognition of its
      multiple comorbid conditions, the importance of aging process over the male
      sexual performance among them its relation with vascular and nitric oxide content
      alteration, as well as penile morphologic changes, and the fact that it is a
      widespread under-reported disease, have established the need of an early
      diagnosis and treatment of this common sexual problem within the general male
      population. CONCLUSION: In this case, morphologic and physiologic mechanisms that
      are involved in the aging process play a key role in the development of sexual
      dysfunction in the absence of any other clinical or medical condition.

PMID- 27872007
TI  - The Role of PDE5 Inhibitors and the NO/cGMP Pathway in Cancer.
AB  - INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used
      clinically for the treatment of erectile dysfunction, acting on the nitric
      oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Simultaneously,
      researchers have elucidated the roles that this pathway plays in the regulation
      of cell proliferation, tumor development, and progression. As a result, our
      knowledge of PDE5i and cancer biology has expanded and provides an integration
      that holds great promise for some, but concern for others. AIM: This review
      evaluates the role of PDE5i and the NO/cGMP signaling pathway in the pathogenesis
      and prevention of various malignancies. METHODS: A literature review was
      performed with regard to the role of NO/cGMP pathway in tumor formation and
      prevention in preclinical and clinical studies. Studies that utilized PDE5i to
      further explore the involvement of this pathway also were included. MAIN OUTCOME
      MEASURES: To evaluate whether PDE5i provide a potential benefit for treating
      and/or preventing malignancies; or if they create potential harm leading to the
      development of these malignancies. RESULTS: The best available data suggest that
      the interactions between PDE5i and cancer are tumor- and tissue-specific.
      Currently, the effect of PDE5i use on melanoma development is being debated.
      Further clinical controversy lies in PDE5i use for penile rehabilitation after
      nerve-sparing prostate cancer surgery. Preclinical studies suggest that PDE5
      inhibition could lead to a decreased risk of developing colorectal and breast
      cancer, leukemia, and myeloma. PDE5i also may provide an additional antitumor
      immune response. Finally, researchers have demonstrated a synergistic effect from
      combining PDE5i with current chemotherapeutic regimens. CONCLUSION: Currently,
      there are inadequate data to make any conclusive statements regarding the role of
      PDE5i in cancer pathogenesis and how to alter clinical management. In order to
      create appropriate clinical guidelines, further experimental and clinical
      evidence is required.

PMID- 27872009
TI  - Molecular details on gilthead sea bream (Sparus aurata) sensitivity to low water
      temperatures from 1H NMR metabolomics.
AB  - Biometric and metabolic responses of gilthead sea bream to cold challenge are
      described following a growth trial divided into three water temperature steps,
      namely cooling, cold maintenance and recovery. Experimental data provide a useful
      description of fish response to thermal stress at both zootechnical and molecular
      level. Although no mortality has been observed, Nuclear Magnetic Resonance-based
      metabolomics confirms the marked sensitivity of this fish species to low water
      temperature, and explains some key molecular events associated to fish response
      to cold. Increase in hepatosomatic index is associated to liver fat accumulation,
      as a consequence of lipid mobilization from muscle and other extrahepatic
      tissues, and metabolic rearrangements linked to homeoviscous adaptation of
      cellular membranes are observed. Following primary responses to descending
      temperature from 18 degrees C to 11 degrees C, the energetic metabolism (insulin
      signaling, glycolysis) is first clearly affected; then, at constant low water
      temperature (11 degrees C), the most perturbed metabolic pathways are related to
      methionine cycle in liver, while osmoregulatory function is exerted by TMAO in
      muscle. Water temperature recovery from 11 degrees C to 18 degrees C stimulates
      gluconeogenesis and glycogen synthesis activities at hepatic level, although the
      rate of a thermo-compensatory response seems to be slower than that of the
      cooling phase. The obtained results are intended to guide novel high-performance
      feed formulations for gilthead sea bream reared during winter.

PMID- 27872010
TI  - Forkhead box O1 in grass carp Ctenopharyngodon idella: Molecular
      characterization, gene structure, tissue distribution and mRNA expression in
      insulin-inhibited adipocyte lipolysis.
AB  - Factor forkhead box O1 (FoxO1) is a transcription factor and plays an important
      role in insulin-mediated lipid metabolism. In the present study, two distinct
      FoxO1 cDNAs, designated FoxO1a and FoxO1b, were firstly isolated and
      characterized from grass carp Ctenopharyngodon idella, encoding peptides of 654
      and 631 amino acids, respectively. Phylogenetic and synteny analyses suggested
      that FoxO1a and FoxO1b were derived from paralogous genes that could be
      originated from teleost-specific genome duplication (TSGD) event. Analysis of the
      exon-intron structures clarified that grass carp FoxO1a and FoxO1b comprise 3
      coding exons and contain a extra intron compared with human and mouse FoxO1. Both
      FoxO1a and FoxO1b mRNAs were expressed in a wide range of tissues, but the
      abundance of each FoxO1 mRNA showed the tissue- dependent expression patterns.
      Time-course analysis of FoxO1 expressions indicated that the level of FoxO1a mRNA
      reached almost maximal level at day 2, while that of FoxO1b mRNA reached almost
      maximal level at day 4 during grass carp primary preadipocyte differentiation. In
      insulin-inhibited adipocyte lipolysis, only FoxO1a showed a significant decrease
      in adipocyte, indicating that two FoxO1 isoforms may serve somewhat different
      roles in the regulation of lipolysis by insulin. These results suggested that
      grass carp FoxO1a and FoxO1b may play different roles in tissues, and their
      expression levels were differently modulated by insulin in adipocyte.

PMID- 27872008
TI  - The Genetic Basis of Peyronie Disease: A Review.
AB  - INTRODUCTION: Peyronie disease (PD) is a progressive fibrotic disorder of the
      penile tunica albuginea that results in fibrotic penile plaques and can lead to
      penile deformity. Characterized by aberrant fibrosis resulting in part from the
      persistence of myofibroblasts and altered gene expression, the molecular factors
      underpinning PD and other related fibrotic diatheses are just being elucidated. A
      genetic link to PD was first identified three decades ago using pedigree
      analyses. However, the specific genetic factors that predispose patients to
      aberrant fibrosis remain unknown, and the relations between these fibrotic
      conditions and other heritable diseases, including malignancy, are
      uncharacterized. AIM: To review the current landscape linking molecular and
      genetic factors to aberrant fibrosis in PD and related fibrotic diatheses,
      including Dupuytren disease. METHODS: Review and evaluation of the literature
      from 1970 to the present for genetic factors associated with PD were performed.
      MAIN OUTCOME MEASURES: Data describing the genetic factors associated with PD
      were obtained. RESULTS: We describe the known structural chromosomal
      abnormalities and single-nucleotide polymorphisms associated with fibrotic
      diatheses and discuss the spectrum of differential gene expression data comparing
      normal tissues with those derived from men with PD or Dupuytren disease. We
      discuss epigenetic mechanisms that might regulate gene expression and alter
      predisposition to fibrosis. CONCLUSION: Although the current understanding of the
      genetic factors associated with PD is limited, significant advances have been
      made during the past three decades. Further research is necessary to provide a
      more comprehensive understanding of the landscape of genetic factors responsible
      for the development of PD.

PMID- 27872012
TI  - Biomimetic collagen/elastin meshes for ventral hernia repair in a rat model.
AB  - : Ventral hernia repair remains a major clinical need. Herein, we formulated a
      type I collagen/elastin crosslinked blend (CollE) for the fabrication of
      biomimetic meshes for ventral hernia repair. To evaluate the effect of
      architecture on the performance of the implants, CollE was formulated both as
      flat sheets (CollE Sheets) and porous scaffolds (CollE Scaffolds). The
      morphology, hydrophylicity and in vitro degradation were assessed by SEM, water
      contact angle and differential scanning calorimetry, respectively. The stiffness
      of the meshes was determined using a constant stretch rate uniaxial tensile test,
      and compared to that of native tissue. CollE Sheets and Scaffolds were tested in
      vitro with human bone marrow-derived mesenchymal stem cells (h-BM-MSC), and
      finally implanted in a rat ventral hernia model. Neovascularization and tissue
      regeneration within the implants was evaluated at 6weeks, by histology,
      immunofluorescence, and q-PCR. It was found that CollE Sheets and Scaffolds were
      not only biomechanically sturdy enough to provide immediate repair of the hernia
      defect, but also promoted tissue restoration in only 6weeks. In fact, the
      presence of elastin enhanced the neovascularization in both sheets and scaffolds.
      Overall, CollE Scaffolds displayed mechanical properties more closely resembling
      those of native tissue, and induced higher gene expression of the entire marker
      genes tested, associated with de novo matrix deposition, angiogenesis,
      adipogenesis and skeletal muscles, compared to CollE Sheets. Altogether, this
      data suggests that the improved mechanical properties and bioactivity of CollE
      Sheets and Scaffolds make them valuable candidates for applications of ventral
      hernia repair. STATEMENT OF SIGNIFICANCE: Due to the elevated annual number of
      ventral hernia repair in the US, the lack of successful grafts, the design of
      innovative biomimetic meshes has become a prime focus in tissue engineering, to
      promote the repair of the abdominal wall, avoid recurrence. Our meshes (CollE
      Sheets and Scaffolds) not only showed promising mechanical performance, but also
      allowed for an efficient neovascularization, resulting in new adipose and muscle
      tissue formation within the implant, in only 6weeks. In addition, our meshes
      allowed for the use of the same surgical procedure utilized in clinical practice,
      with the commercially available grafts. This study represents a significant step
      in the design of bioactive acellular off-the-shelf biomimetic meshes for ventral
      hernia repair.

PMID- 27872011
TI  - Aminoclay as a highly effective cationic vehicle for enhancing adenovirus
      mediated gene transfer through nanobiohybrid complex formation.
AB  - : Electrostatic complexation of adenovirus (Ad) with cationic lipids or polymers
      has been shown to be an effective means for overcoming the limitations of
      adenoviral vectors and enhancing gene-transfer efficacy. However, such
      complexation causes cytotoxicity, limiting the use of this strategy. The present
      study explored the potential of 3-aminopropyl functionalized magnesium
      phyllosilicate (aminoclay) as a cationic vehicle for improving Ad-mediated gene
      transfer without inducing cytotoxicity. Aminoclay complexation produced a dose
      dependent increase in Ad-mediated transgene expression in both Ad infection
      sensitive and -refractory cells, thereby greatly lowering the Ad dose required
      for transgene expression. Unlike the case for cationic lipids (Lipofectamine) or
      polymers (Polybrene), the enhancement effect of aminoclay was not accompanied by
      significant cytotoxicity regardless of cell lines and it was not observed for
      nonviral plasmid vectors. Physical characterization studies revealed that
      nanobiohybrid complexes formed between aminoclay and Ad particles through
      electrostatic interactions, creating aggregates of Ad particles whose surface was
      shielded with aminoclay nanosheet oligomers. It appears that aminoclay
      complexation changes the surface charge of Ad particles from a negative to a
      highly positive value and thus increases Ad binding to cellular membranes,
      thereby providing an additional cellular entry mechanism, namely caveolae
      dependent endocytosis. Aminoclay-Ad nanobiohybrids may serve as a next-generation
      efficient, versatile and biocompatible gene-delivery carrier. STATEMENT OF
      SIGNIFICANCE: Electrostatic complexation of adenovirus with cationic materials
      has been shown to be an effective means for enhancing gene-transfer efficacy in
      vitro. However, such complexation causes cytotoxicity, limiting the use of this
      strategy. The present study explored the potential of a synthesized organoclay 3
      aminopropyl functionalized magnesium phyllosilicate (aminoclay) as a cationic
      vehicle for improving Ad-mediated gene transfer. Our data indicate that
      nanobiohybrid complexes form between aminoclay and Ad particles through
      electrostatic interactions, thereby greatly enhancing Ad-mediated gene transfer.
      Unlike the case for either cationic lipids or cationic polymers, the enhancement
      effect of aminoclay was not accompanied by significant cytotoxicity regardless of
      cell lines. Our findings in this work highlight that aminoclay-Ad nanobiohybrids
      may serve as a next-generation efficient and biocompatible gene-delivery carrier.

PMID- 27872013
TI  - The synergic role of collagen and citrate in stabilizing amorphous calcium
      phosphate precursors with platy morphology.
AB  - : Bioinspired in vitro collagen mineralization experiments have been performed in
      the presence of citrate and the combined role of the two bone organic matrix
      components in controlling mineral formation was investigated for the first time.
      Mineralized and non-mineralized collagen fibrils have been in depth characterized
      by combining small- and wide-angle X-ray scattering (SAXS/WAXS) techniques with
      Atomic Force Microscopy (AFM) imaging. A synergic effect of collagen and citrate
      in driving the formation of long-term stable amorphous calcium phosphate (ACP)
      nanoparticles with platy morphology was found. AFM images on mineralized collagen
      fibrils revealed that some of the ACP nanoparticles were deposited on the
      intramolecular nanoscopic holes of collagen fibrils. STATEMENT OF SIGNIFICANCE:
      Citrate is an important component of the bone organic matrix but its specific
      role in bone mineralization is presently unclear. In this work, bioinspired in
      vitro collagen mineralization experiments in the presence of citrate have been
      carried out and the combined role of collagen and citrate in controlling mineral
      formation has been addressed for the first time. Through X-ray scattering and
      Atomic Force Microscopy characterizations on mineralized and non-mineralized
      collagen fibrils, we have found that citrate in synergy with collagen stabilizes
      an amorphous calcium phosphate (ACP) phase with platy morphology over one week
      and controls its deposition on collagen fibrils.

PMID- 27872014
TI  - The bone-implant interface of dental implants in humans on the atomic scale.
AB  - : Osseointegration of dental implants occurs on a hierarchy of length scales down
      to the atomic level. A deeper understanding of the complex processes that take
      place at the surface of an implant on the smallest scale is of interest for the
      development of improved biomaterials. To date, transmission electron microscopy
      (TEM) has been utilized for examination of the bone-implant interface, providing
      details on the nanometer level. In this study we show that TEM imaging can be
      complemented with atom probe tomography (APT) to reveal the chemical composition
      of a Ti-based dental implant in a human jaw on the atomic level of resolution. As
      the atom probe technique has equal sensitivity for all elements, it allows for 3
      dimensional characterizations of osseointegrated interfaces with unprecedented
      resolution. The APT reconstructions reveal a Ca-enriched zone in the immediate
      vicinity of the implant surface. A surface oxide of some 5nm thickness was
      measured on the titanium implant, with a sub-stoichiometric composition with
      respect to TiO2. Minor incorporation of Ca into the thin oxide film was also
      evident. We conclude that the APT technique is capable of revealing chemical
      information from the bone-implant interface in 3D with unprecedented resolution,
      thus providing important insights into the mechanisms behind osseointegration.
      STATEMENT OF SIGNIFICANCE: Osseointegration of dental implants occurs on a
      hierarchy of length scales down to the atomic level. A deeper understanding of
      the complex processes that take place at the surface of an implant on the
      smallest scale is of interest for the development of improved biomaterials. To
      date, transmission electron microscopy (TEM) has been utilized for examination of
      the bone-implant interface, providing details on the nanometer level. In this
      study we show that TEM imaging can be complemented with atom probe tomography
      (APT) to reveal the chemical composition of a Ti-based dental implant in a human
      jaw on the atomic level of resolution. Correlative microscopy ensures the
      accuracy of APT reconstructions and helps provide both chemical and structural
      information of the bone-implant interface on the smallest of length scales.

PMID- 27872015
TI  - Self-hardening and thermoresponsive alpha tricalcium phosphate/pluronic pastes.
AB  - : Although calcium phosphate cements (CPCs) are used for bone regeneration in a
      wide range of clinical applications, various physicochemical phenomena are known
      to hinder their potential use in minimally invasive surgery or in highly
      vascularized surgical sites, mainly because of their lack of injectability or
      their low washout resistance. The present work shows that the combination of CPCs
      with an inverse-thermoresponsive hydrogel is a good strategy for finely tuning
      the cohesive and rheological properties of CPCs to achieve clinical acceptable
      injectability to prevent phase separation during implantation and cohesion to
      avoid washout of the paste. The thermoresponsive CPC developed combines alpha
      tricalcium phosphate with an aqueous solution of pluronic F127, which exhibits an
      inverse thermoresponsive behaviour, with a gelling transformation at around body
      temperature. These novel CPCs exhibited temperature-dependent properties.
      Addition of the polymer enhanced the injectability of the paste, even at a low
      liquid-to-powder ratio, and allowed the rheological properties of the cement to
      be tuned, with the injection force decreasing with the temperature of the paste.
      Moreover, the cohesion of the paste was also temperature-dependent and increased
      as the temperature of the host medium increased due to gelling induced in the
      paste. The thermoresponsive cement exhibited excellent cohesion and clinically
      acceptable setting times at 37 degrees C, irrespective of the initial temperature
      of the paste. The addition of pluronic F127 slightly delayed the setting reaction
      in the early stages but did not hinder the full transformation to calcium
      deficient hydroxyapatite. Moreover, the frozen storage of premixed
      thermoresponsive cement pastes was explored, the main physicochemical properties
      of the cements being maintained upon thawing, even after 18months of frozen
      storage. This avoids the need to mix the cement in the operating theatre and
      allows its use off-the-shelf. The reverse thermoresponsive cements studied herein
      open up new perspectives in the surgical field, where the sequential
      gelling/hardening of these novel cements could allow for a better and safer
      clinical application. STATEMENT OF SIGNIFICANCE: Calcium phosphate cements are
      attractive bone substitutes due to their similarity to the bone mineral phase.
      Although they can be injectable, cohesion and stability of the paste are crucial
      in terms of performance and safety. A common strategy is the combination with
      hydrogels. However, this often results in a decrease of viscosity with increasing
      temperature, which can lead to extravasation and particle leakage from the bone
      defect. The preferred evolution would be the opposite: a low viscosity would
      enhance mixing and injection, and an instantaneous increase of viscosity after
      injection would ensure washout resistance to the blood flow. Here we develop for
      the first time a calcium phosphate cement exhibiting reverse thermoresponsive
      properties using a poloxamer featuring inverse thermal gelling.

PMID- 27872016
TI  - Tuberculosis eradication versus control.
AB  - According to the World Health Organization (WHO), 10.4 million people died of
      tuberculosis (TB) in 2015, and the disease is now the number one cause of death
      from a preventable infectious disease worldwide. A bold vision is needed from
      global leaders to end the TB epidemic and plans to this end have been proposed.
      However enthusiasm must be matched by tangible and achievable goals based on the
      science and available funding. In order to reach the target and goals set by the
      WHO End TB Strategy, the challenges for TB eradication need to be addressed. In
      order to achieve the targets, several areas need to be bolstered, including the
      requirement to better identify and treat existing drug-susceptible cases and
      diagnose all the drug-resistant forms of the disease. Although treatment is
      available for most TB patients, stock-outs and other delays are problematic in
      some settings, resulting in ongoing transmission, especially for the drug
      resistant forms of the disease. Despite the fact that a majority of multidrug
      resistant cases are linked to treatment, the cure rate is only 50%, which
      highlights the need for safer, shorter, and more efficacious drug regimens that
      are more tolerable to patients. Prospects for a more efficacious vaccine are
      limited, with no correlates of protection identified; thus the availability of a
      vaccine by 2025 is highly improbable. Support for instituting infection control
      methods should be prioritized to subvert transmission while patients seek
      treatment and care. Finally, more adequate financial mechanisms should be
      instituted to reduce patient expenditures and support national TB programs.
      Moreover, funding to support basic science, drug development, clinical trials,
      vaccine development, diagnostics, and implementation research needs to be secured
      in order to reduce global TB incidence in the future.

PMID- 27872017
TI  - Secondarily documented invasive candidiasis is unpredictable using traditional
      risk factors in non transplant - non-neutropenic adult ICU patients.

PMID- 27872018
TI  - Preventive therapy for latent tuberculosis infection-the promise and the
      challenges.
AB  - Around one third of the world's population may harbour latent tuberculosis
      infection (LTBI), an asymptomatic immunological state that confers a heightened
      risk of subsequently developing tuberculosis (TB). Effectively treating LTBI will
      be essential if the End TB Strategy is to be realized. This review evaluates the
      evidence in relation to the effectiveness of preventive antibiotic therapy to
      treat LTBI due to both drug-susceptible and drug-resistant bacteria. Current
      national and international preventive therapy guidelines are summarized, as well
      as ongoing randomized trials evaluating regimens to prevent drug-resistant TB.
      Populations that may benefit most from screening and treatment for LTBI include
      close contacts of patients with TB (particularly children under 5 years of age)
      and individuals with substantial immunological impairment. The risks and benefits
      of treatment must be carefully balanced for each individual. Electronic decision
      support tools offer one way in which clinicians can help patients to make
      informed decisions. Modelling studies indicate that the expanded use of
      preventive therapy will be essential to achieving substantial reductions in the
      global TB burden. However, the widespread scale-up of screening and treatment
      will require careful consideration of cost-effectiveness, while ensuring the
      drivers of ongoing disease transmission are also addressed.

PMID- 27872019
TI  - Metabotropic glutamate receptors and neurodegenerative diseases.
AB  - Glutamate is the most important excitatory neurotransmitter of the mammalian
      central nervous system (CNS), playing an important role in memory, synaptic
      plasticity and neuronal development. However, glutamate overstimulation is also
      implicated in neuronal cell death. There are two major types of glutamate
      receptors: ionotropic and metabotropic. Thus far, eight metabotropic glutamate
      receptors (mGluRs) subtypes have been characterized and are divided into three
      subgroups based on sequence homology and cell signaling activation. mGluRs
      activate a wide variety of cell signaling pathways by G protein-coupled pathways
      or via G protein-independent cell signaling activation. Moreover, these receptors
      exhibit widespread distribution in the CNS and are implicated in several
      neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's
      disease (PD) and Huntington's disease (HD). This review aims to discuss the
      latest updates concerning mGluRs and their role in neurodegenerative diseases.
      mGluRs agonists and antagonists as well as positive and negative allosteric
      modulators have been tested in several animal models of neurodegenerative
      diseases. Furthermore, mGluR knockout mouse models have been crossed to mouse
      models of AD and HD, providing important data about mGluRs role in
      neurodegenerative disease progression. Thus, mGluRs constitute potential
      therapeutic targets for the development of therapies to treat neurodegenerative
      diseases.

PMID- 27872020
TI  - Niclosamide ethanolamine inhibits artery constriction.
AB  - We previously demonstrated that the typical mitochondrial uncoupler carbonyl
      cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP
      was used only as a pharmacological tool. Niclosamide is an anthelmintic drug
      approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and
      has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The
      aim of the present study was to elucidate the vasoactivity of NEN and the
      potential mechanisms. Isometric tension of rat mesenteric artery and thoracic
      aorta was recorded by using multi-wire myograph system. The protein levels were
      measured by using western blot techniques. Niclosamide ethanolamine (NEN)
      treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction,
      and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat
      mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE
      and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in
      vascular smooth muscle cells (A10) and activated AMP-activated protein kinase
      (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was
      attenuated in AMPKalpha1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid
      and thapsigargin, but not KATP channel blockers glibenclamide and 5
      hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric
      arteries. NEN treatment increased cytosolic [Ca2+]i and depolarized mitochondrial
      membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt
      form showed the similar vasoactivity as NEN in rat mesenteric arteries.
      Niclosamide ethanolamine inhibits artery constriction, indicating that it would
      be promising to be developed as an anti-hypertensive drug or it would induce
      vasodilation-related side effects when absorbed in vivo.

PMID- 27872021
TI  - Hypoactive Sexual Desire Disorder: A Review of Epidemiology, Biopsychology,
      Diagnosis, and Treatment.
AB  - INTRODUCTION: Hypoactive Sexual Desire Disorder (HSDD) is defined in the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Revised
      (DSM-IV-TR) as persistent deficient sexual fantasies and desire for sexual
      activity that causes marked distress or interpersonal difficulty. In the
      Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),
      HSDD has been subsumed by Female Sexual Interest/Arousal Disorder. However,
      decades of research based on DSM-IV-TR HSDD criteria form the foundation of our
      understanding of the essential symptom of distressing low sexual desire, its
      epidemiology, clinical management, and treatment. AIM: This publication reviews
      the state of knowledge about HSDD. METHODS: A literature search was performed
      using terms HSDD and female sexual dysfunction (FSD). MAIN OUTCOME MEASURES:
      Physicians acknowledge that FSD is common and distressing; however, they
      infrequently address it, citing low confidence, time constraints, and lack of
      treatment as barriers. RESULTS: HSDD is present in 8.9% of women ages 18 to 44,
      12.3% ages 45 to 64, and 7.4% over 65. Although low sexual desire increases with
      age, distress decreases; so prevalence of HSDD remains relatively constant across
      age. HSDD is associated with lower health-related quality of life; lower general
      happiness and satisfaction with partners; and more frequent negative emotional
      states. HSDD is underdetected and undertreated. Less than half of patients with
      sexual problems seek help from or initiate discussions with physicians. Patients
      are inhibited by fear of embarrassing physicians and believe that physicians
      should initiate discussions. The Decreased Sexual Desire Screener, a tool for
      detecting and diagnosing HSDD, is validated for use in general practice.
      CONCLUSION: Women can benefit from intervention in primary care, behavioral
      health and sexual medicine settings. Psychotherapeutic and pharmacological
      interventions aim to enhance sexual excitatory process and decrease inhibitory
      processes. Flibanserin, the first centrally acting daily medication for HSDD, was
      recently approved in the US for premenopausal women.

PMID- 27872022
TI  - Comparing the Prevalence, Risk Factors, and Repercussions of Postpartum Genito
      Pelvic Pain and Dyspareunia.
AB  - INTRODUCTION: Childbirth is a risk factor for developing genito-pelvic pain
      and/or dyspareunia during the postpartum period and potentially in the longer
      term. These two types of pain can occur simultaneously or sequentially and could
      be affected by different risk factors and have a range of repercussions to
      women's lives, including their sexual functioning. AIM: This study reviewed the
      available evidence to compare and contrast the prevalence, risk factors, and
      repercussions of postpartum genito-pelvic pain vs dyspareunia. METHODS: All
      available data related to postpartum genito-pelvic pain and dyspareunia were
      reviewed. MAIN OUTCOME MEASURES: A description of the prevalence, risk factors,
      and sexual and psychological consequences of postpartum genito-pelvic pain and
      dyspareunia and the methodologic limitations of previous studies. RESULTS: The
      prevalence of postpartum genito-pelvic pain is much lower than that of postpartum
      dyspareunia. There is evidence of converging and differential risk factors for
      acute and persistent experiences of these two types of pain. Postpartum genito
      pelvic pain and dyspareunia are associated with impaired sexual functioning.
      Rarely are these pain experiences examined together to make direct comparisons.
      CONCLUSION: There has been a critical lack of studies examining postpartum genito
      pelvic pain and dyspareunia together and integrating biomedical and psychosocial
      risk factors. This approach should be spearheaded by a multidisciplinary group of
      researchers of diverse and relevant expertise, including obstetricians,
      gynecologists, anesthesiologists, and psychologists.

PMID- 27872023
TI  - Multiple Orgasms in Men-What We Know So Far.
AB  - INTRODUCTION: There is much popular discussion on strategies to facilitate
      multiple orgasms in men (ie, 100,000+ hits in Google), yet the topic has not
      received an objective comprehensive review in the literature. AIM: To review the
      literature on male multiple orgasms. METHODS: We searched the literature for
      publications on "male multiple orgasms" and factors influencing male multiple
      orgasms in Google, PubMed, and PsychINFO. This yielded 15 relevant publications.
      MAIN OUTCOME MEASURES: A comprehensive overview on the topic of male multiple
      orgasms and factors that influence the propensity of men to experience multiple
      orgasms. RESULTS: Few men are multiorgasmic: <10% for those in their 20s, and <7%
      after the age of 30. The literature suggests 2 types of male multiple orgasms:
      "sporadic" multiorgasms, with interorgasmic intervals of several minutes, and
      "condensed" multiorgasms, with bursts of 2-4 orgasms within a few seconds to 2
      minutes. Multiple orgasms appear physiologically similar to the single orgasm in
      mono-orgasmic men. However, in a single case study, a multiorgasmic man did not
      experience with his first orgasm the prolactin surge that usually occurs with
      orgasm in mono-orgasmic men. Various factors may facilitate multiple orgasms: (1)
      practicing to have an orgasm without ejaculation; (2) using psychostimulant
      drugs; (3) having multiple and/or novel sexual partners; or (4) using sex toys to
      enhance tactile stimulation. However, confirmatory physiological data on any of
      these factors are few. In some cases, the ability to experience multiple orgasms
      may increase after medical procedures that reduce ejaculation (eg, prostatectomy
      or castration), but what factor(s) influence this phenomenon is poorly
      investigated. CONCLUSION: Despite popular interest, the topic of male multiple
      orgasms has received surprisingly little scientific assessment. The role of
      ejaculation and physiological change during the refractory period in inhibiting
      multiple orgasms has barely been investigated.

PMID- 27872024
TI  - Floppy Glans Syndrome: Pathogenesis and Treatment.
AB  - INTRODUCTION: Floppy glans syndrome (FGS) is a potential complication of penile
      prosthesis placement in patients with erectile dysfunction. FGS affects a very
      small proportion of these patients, and it can manifest in a ventral, dorsal, or
      lateral droop of a hypermobile glans, which can cause affected patients to
      complain of painful, unsatisfying, or otherwise difficult attempts at sexual
      intercourse. Incorrect cylinder sizing can even result in extreme conditions such
      as flail penis or S-shaped deformity. AIM: The aim of this review is to outline
      the types, causes, and management options for FGS. METHODS: This review was
      conducted after a thorough literature search in addition to experience managing
      FGS at the authors' institution. MAIN OUTCOME MEASURES: Clarification of the
      nomenclature for FGS, supersonic transporter deformity, flail penis, and
      crossover to define, diagnose, and treat these conditions. RESULTS: In many cases
      of FGS, poor intraoperative prosthetic cylinder positioning and sizing can lead
      to insufficient compression of the deep dorsal and circumflex veins between the
      Buck fascia and the corpora cavernosa, even when cylinders are maximally
      inflated. When the adjacent tissue does not adequately restrict blood flow
      through these vessels, then glanular tumescence becomes increasingly difficult to
      achieve, particularly in patients with severe erectile dysfunction who have poor
      glanular blood flow at baseline. FGS also can be a result of poor underlying
      glanular structural support. Thus, droop is possible even when cylinders have an
      appropriate size and position. Treatment options range from medical management to
      surgical correction. Distal penoplasty and glanulopexy have been described as
      effective methods of correcting the FGS deformity and avoiding the more invasive
      option of prosthetic cylinder replacement. These options are especially valuable
      in patients who undergo adequate cylinder sizing intraoperatively. CONCLUSION:
      FGS is not monolithic, and careful diagnosis is essential to determining the
      appropriate treatment course.

PMID- 27872025
TI  - Contemporary Review of Artificial Urinary Sphincters for Male Stress Urinary
      Incontinence.
AB  - INTRODUCTION: The most common cause of urinary incontinence in men after radical
      prostatectomy is intrinsic sphincter deficiency, which can affect long-term
      quality of life. The prevalence of stress urinary incontinence (SUI) after
      radical prostatectomy has been reported to be 2.5% to 90%. For patients with
      moderate to severe male SUI, the artificial urinary sphincter (AUS) is considered
      the gold standard in surgical treatment. AIM: To review the available literature
      on the development, patient selection, surgical technique, complications, and
      management of AUS for male SUI. METHODS: A literature review was performed
      through PubMed from 1947 to 2015 regarding AUS for male SUI. MAIN OUTCOME
      MEASURES: To assess various surgical techniques related to AUS insertion,
      outcomes, and complications and to offer recommendations regarding management of
      complications. RESULTS: The AUS can be placed through a perineal or trans-scrotal
      incision, particularly in the setting of dual insertion of an AUS and an
      inflatable penile prosthesis. The most commonly used cuff is 4.0 cm. The efficacy
      of InhibiZone is debatable. Pressure-regulating balloons can be filled with
      saline or contrast material and can be placed in an orthotopic or an ectopic
      location. In a systematic review of the literature, dry or improved continence
      rates are achieved in 79% of patients, with 90% reporting satisfaction and
      improved quality-of-life index scores after surgery. The most common AUS
      complications include a nonfunctioning device, sub-cuff atrophy, erosion, and
      infection. These complications are managed by strategies such as cuff downsizing,
      tandem cuff placement, and explantation. Dual AUS and inflatable penile
      prosthesis insertion is feasible for patients with SUI and erectile dysfunction.
      CONCLUSION: The AUS is a durable and effective device for the management of SUI.
      Surgeons should be versed in the different device components, their potential
      complications, and their management.

PMID- 27872026
TI  - Male and Female Sexual Dysfunction in a Rapidly Changing Cultural Environment:
      Addressing Gender Equality versus Equivalence in the Bedroom.
AB  - INTRODUCTION: The socio-sexual climate in Western cultures is changing at an
      astounding rate. Never before have societal expectations about gender roles
      shifted so radically, transforming our understanding of what it means to be a
      sexual man or woman today. We have observed that confusion regarding masculine
      and feminine roles within long-term committed relationships can represent
      challenges for the treatment of sexual dysfunction. Despite the relevance to
      sexual medicine, sexual medicine specialists have largely avoided this
      controversial topic. AIM: To review the current literature relating to
      heterosexual gender roles and sexual intimacy, to offer perspective and context
      on this issue, and to propose an approach to the man, woman, or couple based in
      evolutionary theory that we have found useful in our extensive clinical
      experiences. METHODS: We reviewed the English-language peer-reviewed literature,
      primarily from 2000 through 2015, that addressed the impact of heterosexual
      gender role expression on sexual intimacy in long-term committed relationships.
      MAIN OUTCOME MEASURES: Main outcomes include a review of the applicable
      literature and an assessment of the literature's relevance for patients and
      practitioners of sexual medicine. An alternative context for understanding
      heterosexual gender expression grounded in evolutionary theory is provided, as is
      a new treatment perspective based on our work as a sex therapist and an
      urologist. RESULTS: The impact of gender expression on sexual experience might be
      impossible to ascertain fully because it is difficult to quantify in research,
      independently and especially in combination. Furthermore, existing research is
      fraught with challenges and inadequacies. CONCLUSION: Although we acknowledge and
      affirm the critical importance of gender equality, modern conceptualizations of
      gender in the literature ignore pertinent evolutionary adaptations and might be
      minimally applicable to sexual medicine patients. More research is needed. We
      propose that equality of genders does not necessarily mean similarity of genders,
      at least in sexual medicine.

PMID- 27872027
TI  - How the Emotional Motor System Controls the Pelvic Organs.
AB  - INTRODUCTION: The brain has two goals: survival of the individual and survival of
      the species. It ensures that the body resides in safe circumstances and can
      obtain sufficient drink and food. It also has to produce and protect offspring.
      Its most important tool is its motor system, which consists of the voluntary and
      emotional motor systems. AIM: To explain how the brain uses its emotional motor
      system to control the pelvic organs. METHODS: Anatomic and physiologic data in
      cats and humans are used to find out how this motor system works and what parts
      of the brain and brainstem are involved. MAIN OUTCOME MEASURES: Main outcome is
      that the brain control of the pelvic organs is a specific descending system.
      RESULTS: The pelvic organs are innervated by the sacral parasympathetic
      motoneurons, which are controlled by a specific group of neurons in the pontine
      brainstem, the pelvic organ stimulating center (POSC). Through long descending
      pathways, this POSC generates micturition, defecation, and sexual activities by
      stimulating different groups of sacral parasympathetic motoneurons. In turn the
      POSC is driven by the periaqueductal gray (PAG), which receives, through the
      sacral cord, precise information regarding the situation in all pelvic organs. In
      addition, the PAG receives instructions from higher brain levels such as the
      amygdala, bed nucleus of the stria terminalis, and various regions of the
      hypothalamus. Notably, in humans, the most important brain region having access
      to the PAG is the medial orbitofrontal cortex, which is deactivated in women with
      hypoactive sexual desire disorder. CONCLUSION: In women with hypoactive sexual
      desire disorder, deactivation of their medial orbitofrontal cortex produces a
      decrease in PAG-POSC activation, causing absence of vaginal vasocongestion and
      lubrication and decreased sexual behavior in general. It often leads to major
      problems in their personal circumstances. The question is whether new drugs can
      cure this.

PMID- 27872028
TI  - Monogamy and Nonmonogamy: Evolutionary Considerations and Treatment Challenges.
AB  - INTRODUCTION: Few topics generate such controversy and emotional reactivity as
      the nature of human mating behavior. Unfortunately, and potentially to the
      detriment of good patient care, sexual medicine practitioners have largely
      avoided this matter. An understanding of the scientific literature can empower
      practitioners to more effectively confront the inevitable monogamy and
      nonmonogamy challenges present in research and clinical practice. AIM: To review
      and summarize relevant scientific literature as a context to evaluate the more
      common myths and misunderstanding relating to the practice of monogamy and
      nonmonogamy in humans. This review also is intended to promote a discussion of
      the ways human mating strategies may impact sexual function and dysfunction for
      the individual and couple. METHODS: A review of English written peer-reviewed
      evolutionary, anthropological, neuropsychiatric, zoological research, and other
      scholarly texts was conducted. Work published between 2000 and 2016 concentrating
      on evolutionary theory, long- and short-term mating strategies in primates and
      most specifically in humans, and consensual nonmonogamy was highlighted. MAIN
      OUTCOME MEASURES: Main outcomes included a brief explanation of evolutionary
      theory and a review of relevant literature regarding long- and short-term mating
      behaviors and consensual nonmonogamy. RESULTS: Serial sexual and social monogamy
      is the norm for humans. Across time and cultures, humans have adapted both long-
      and short-term mating strategies that are used flexibly, and sometimes
      simultaneously, based on unique personal, social, and environmental
      circumstances. CONCLUSION: Human mating behavior is individualistic, the result
      of numerous biopsychosocial influences. The clinician cannot assume that an
      individual presenting as a patient maintains a monogamy-valued view of his or her
      intimate relationship. Patients may experience conflict between the cultural
      monogamous ideal and their actual sexual behaviors. This conflict may be critical
      in understanding a patient's sexual concerns and in treatment planning. Awareness
      of these issues will aid the practitioner in sexual medicine.

PMID- 27872029
TI  - Association Between Infertility and Sexual Dysfunction in Men and Women.
AB  - INTRODUCTION: The relation between infertility and sexual dysfunction can be
      reciprocal. Causes of sexual dysfunction that affect fertility include erectile
      dysfunction, Peyronie's disease (abnormal penile curvature), low libido,
      ejaculatory disorders in men, and genito-pelvic pain/penetration disorder (GPPPD)
      and low sexual desire in women. AIM: To review the association between
      infertility and sexual dysfunction and discuss current management strategies to
      address sexual disorders in couples with infertility. METHODS: Peer-reviewed
      publications from PubMed published from 1980 through February 2016 were
      identified that related to sexual dysfunction and infertility in men and women.
      MAIN OUTCOME MEASURES: Pathophysiology and management approach of erectile
      dysfunction, Peyronie's disease, low libido, ejaculatory disorders in men, and
      GPPPD and low sexual desire in women and how each etiology contributes to sexual
      dysfunction and infertility in the couple. RESULTS: Treating the infertile couple
      with sexual dysfunction involves addressing underlying conditions such as
      psychogenic erectile dysfunction, low testosterone, Peyronie's disease in men,
      and GPPPD and low sexual desire in women. Psychogenic erectile dysfunction can be
      successfully treated with phosphodiesterase inhibitors. Low testosterone is often
      identified in men with infertility, but testosterone therapy is contraindicated
      in men attempting conception. Men with Peyronie's disease have a new treatment
      option to address their penile curvature-collagenase Clostridium histolyticum
      injection directly into the penile plaque. GPPPD is a broad disorder that
      includes vulvodynia and vaginismus and can be treated with topical lubricants and
      moisturizers. We must address psychosocial factors in women with low sexual
      desire. Flibanserin and transdermal testosterone (off-label) are novel therapies
      for women with low sexual desire. CONCLUSION: Sexual dysfunction in a couple with
      infertility is a complex issue. Management of infertility and sexual dysfunction
      should involve appropriate medical therapy and addressing the psychosocial
      concerns of the couple.

PMID- 27872030
TI  - Male Sexual Function and Smoking.
AB  - INTRODUCTION: Erectile dysfunction (ED) is a common disorder that has many
      potential etiologies, including hormonal imbalances, psychogenic factors,
      neurologic disorders, vascular insufficiency, and other risk factors. Cigarette
      smoking has been well established as a risk factor for cardiovascular disease and
      stroke, but the relation between smoking and ED is less frequently considered.
      AIM: To review the current literature that analyzes the association between
      cigarette smoking and ED. METHODS: The PubMed database was searched using the
      terms erectile dysfunction and smoking and erectile dysfunction and tobacco
      through December 2015. MAIN OUTCOME MEASURES: Main outcome measures were
      significant changes in erectile function in relation to smoking status. RESULTS:
      Eighty-three studies and articles were reviewed. Multiple human studies, animal
      studies, case series, cross-sectional, and cohort studies analyzed the relation
      between smoking or nicotine and ED. CONCLUSION: There is substantial evidence
      showing that cigarette smoking is a risk factor for ED. Multiple human, animal,
      case series, cross-sectional, and cohort studies support this conclusion. A
      positive dose-response relation also is suggested such that increased quantity
      and duration of smoking correlate with a higher risk of ED. Smoking cessation can
      lead to recovery of erectile function, but only if limited lifetime smoking
      exposure exists. Smoking contributes to ED in different ways, especially by
      causing penile vasospasm and increased sympathetic nervous system tone.

PMID- 27872031
TI  - Penile Prosthesis Infections-A Review of Risk Factors, Prevention, and Treatment.
AB  - INTRODUCTION: Inflatable penile prosthesis (IPP) surgery has been performed for
      more than 40 years. IPP infection rates have decreased owing to advances in
      manufacturing and surgical technique but have remained a devastating
      complication. AIMS: To describe the pathophysiology of infections, examine
      evidence associating clinical risk factors with IPP infection, assess the benefit
      of techniques aimed at preventing and managing infection, and discuss future
      directions. METHODS: PubMed and Google Scholar were searched for studies relating
      to IPP infections. MAIN OUTCOME MEASURES: A comprehensive review of the
      literature on IPP infections focusing on predisposing factors and ways to prevent
      and treat. RESULTS: There are two types of IPP infections: those caused by
      coagulase-negative Staphylococcus species, which present mildly, and those caused
      by organisms that are more virulent and systemically toxic. Biofilm on devices
      protects bacteria from immunologic responses and antibiotics. Much research has
      targeted biofilm. Spinal cord injury, IPP revision, and longer operative times
      predispose to IPP infection. Other factors, such as diabetes, immunosuppression,
      and concomitant surgeries, lack sufficient evidence to determine conclusively.
      Methods that decrease infections include using infused prostheses and adhering to
      surgical techniques that avoid prolonged wound exposure. Techniques that might
      prevent IPP infection but lack definitive evidence are using postoperative
      antibiotics past 24 hours, shaving with clippers, and prepping with chlorhexidine
      alcohol. Different treatments for IPP infections exist. Antibiotics should be
      followed by explantation if no improvement occurs. Device replacement can be
      immediate or delayed depending on infection severity and other variables such as
      erosion. Various techniques are proposed to prevent corporal fibrosis after IPP
      removal. CONCLUSION: We reviewed studies to determine true risk factors and the
      techniques that have true impact on infection prevention. Newer studies focusing
      on prevention and disruption of biofilm will be key in advancing the best
      outcomes.

PMID- 27872032
TI  - Web-Based Antismoking Advertising to Promote Smoking Cessation: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Although hundreds of millions of dollars are spent each year on
      public health advertising, the advertisement content, design, and placement are
      usually developed by intuition rather than research. OBJECTIVE: The objective of
      our study was to develop a methodology for testing Web-based advertisements to
      promote smoking cessation. METHODS: We developed 10 advertisements that varied by
      their content (those that empower viewers to quit, help viewers to quit, or
      discuss the effects of smoking). We then conducted a series of Web-based
      randomized controlled trials that explored the effects of exposing users of
      Microsoft's Bing search engine to antismoking advertisements that differed by
      content, placement, or other characteristics. Finally, we followed users to
      explore whether they conducted subsequent searches for smoking cessation products
      or services. RESULTS: The advertisements were shown 710,106 times and clicked on
      1167 times. In general, empowering advertisements had the greatest impact (hazard
      ratio [HR] 2.6, standard error [SE] 0.09 relative to nonempowering
      advertisements), but we observed significant variations by gender. For instance,
      we found that men exposed to smoking cessation advertisements were less likely
      than women to subsequently conduct smoking cessation searches (HR 0.2, SE 0.07),
      but that this likelihood increased 3.5 times in men exposed to advertisements
      containing empowering content. Women were more influenced by advertisements that
      emphasized the health effects of smoking. We also found that appearing at the top
      right of the page (HR 2.1, SE 0.07) or at the bottom rather than the top of a
      list (HR 1.1, SE 0.02) can improve smoking cessation advertisements'
      effectiveness in prompting future searches related to smoking cessation.
      CONCLUSIONS: Advertising should be targeted to different demographic groups in
      ways that are not always intuitive. Our study provides a method for testing the
      effectiveness of Web-based antismoking advertisements and demonstrates the
      importance of advertisements that are tailored according to specific
      demographics.

PMID- 27872033
TI  - A Review of Visual Representations of Physiologic Data.
AB  - BACKGROUND: Physiological data is derived from electrodes attached directly to
      patients. Modern patient monitors are capable of sampling data at frequencies in
      the range of several million bits every hour. Hence the potential for cognitive
      threat arising from information overload and diminished situational awareness
      becomes increasingly relevant. A systematic review was conducted to identify
      novel visual representations of physiologic data that address cognitive,
      analytic, and monitoring requirements in critical care environments. OBJECTIVE:
      The aims of this review were to identify knowledge pertaining to (1) support for
      conveying event information via tri-event parameters; (2) identification of the
      use of visual variables across all physiologic representations; (3) aspects of
      effective design principles and methodology; (4) frequency of expert
      consultations; (5) support for user engagement and identifying heuristics for
      future developments. METHODS: A review was completed of papers published as of
      August 2016. Titles were first collected and analyzed using an inclusion
      criteria. Abstracts resulting from the first pass were then analyzed to produce a
      final set of full papers. Each full paper was passed through a data extraction
      form eliciting data for comparative analysis. RESULTS: In total, 39 full papers
      met all criteria and were selected for full review. Results revealed great
      diversity in visual representations of physiological data. Visual representations
      spanned 4 groups including tabular, graph-based, object-based, and metaphoric
      displays. The metaphoric display was the most popular (n=19), followed by
      waveform displays typical to the single-sensor-single-indicator paradigm (n=18),
      and finally object displays (n=9) that utilized spatiotemporal elements to
      highlight changes in physiologic status. Results obtained from experiments and
      evaluations suggest specifics related to the optimal use of visual variables,
      such as color, shape, size, and texture have not been fully understood.
      Relationships between outcomes and the users' involvement in the design process
      also require further investigation. A very limited subset of visual
      representations (n=3) support interactive functionality for basic analysis, while
      only one display allows the user to perform analysis including more than one
      patient. CONCLUSIONS: Results from the review suggest positive outcomes when
      visual representations extend beyond the typical waveform displays; however,
      there remain numerous challenges. In particular, the challenge of extensibility
      limits their applicability to certain subsets or locations, challenge of
      interoperability limits its expressiveness beyond physiologic data, and finally
      the challenge of instantaneity limits the extent of interactive user engagement.

PMID- 27872034
TI  - Test-Enhanced E-Learning Strategies in Postgraduate Medical Education: A
      Randomized Cohort Study.
AB  - BACKGROUND: The optimal design of pedagogical strategies for e-learning in
      graduate and postgraduate medical education remains to be determined. Video-based
      e-learning use is increasing, with initial research suggesting that taking short
      breaks while watching videos (independent of answering test questions) may
      improve learning by focusing attention on the content presented. Interspersed
      test questions may also improve knowledge acquisition and retention. OBJECTIVE:
      To examine the effect of interspersed test questions and periodic breaks on
      immediate knowledge acquisition and retention at 6 months by pediatric residents
      engaged in video-based e-learning. METHODS: First- and second-year pediatric
      residents were randomized to 1 of the following 3 groups: viewing the complete
      video uninterrupted (full video), viewing the video interrupted with unrelated
      logic puzzles (logic puzzles), or viewing the video interrupted with brief
      comprehension test questions (short answer questions). Residents answered pre-
      and post-tests before and after video viewing, followed by a retention test at 6
      months. Primary outcome included comparison of the change in test scores between
      groups. RESULTS: A total of 49 residents completed the initial testing session.
      All 3 learning groups had comparable mean increases in immediate knowledge gain,
      but with no significant differences between groups (F2,46=0.35, P=.71). Thirty
      five residents completed retention testing with comparable degrees of knowledge
      retention in the full video and short answer test questions groups (P<.001), but
      no significant change in the logic puzzles group (F1,32=2.44, P=.13).
      CONCLUSIONS: Improved knowledge gain was not demonstrated among residents
      answering interspersed questions or completing logic puzzles during interrupted
      online video viewing when compared with residents viewing uninterrupted video
      content. However, residents who either participated in uninterrupted video
      viewing or answered interspersed questions during interrupted video viewing
      demonstrated significant knowledge retention at 6 months.

PMID- 27872035
TI  - Practical Issues in Developing a Culturally Tailored Physical Activity Promotion
      Program for Chinese and Korean American Midlife Women: A Pilot Study.
AB  - BACKGROUND: With advances in computer technologies, Web-based interventions are
      widely accepted and welcomed by health care providers and researchers. Although
      the benefits of Web-based interventions on physical activity promotion have been
      documented, the programs have rarely targeted Asian Americans, including Asian
      American midlife women. Subsequently, culturally competent Web-based physical
      activity programs for Asian Americans may be necessary. OBJECTIVE: The purpose of
      our study was to explore practical issues in developing and implementing a
      culturally competent Web-based physical activity promotion program for 2 groups
      of Asian American women-Chinese American and Korean American midlife women-and to
      provide implications for future research. METHODS: While conducting the study,
      the research team members wrote individual memos on issues and their inferences
      on plausible reasons for the issues. The team had group discussions each week and
      kept the minutes of the discussions. Then, the memos and minutes were analyzed
      using a content analysis method. RESULTS: We identified practical issues in 4
      major idea categories: (1) bilingual translators' language orientations, (2)
      cultural sensitivity requirement, (3) low response rate, interest, and retention,
      and (4) issues in implementation logistics. CONCLUSIONS: Based on the issues, we
      make several suggestions for the use of bilingual translators, motivational
      strategies, and implementation logistics.

PMID- 27872036
TI  - Challenges and Opportunities of Big Data in Health Care: A Systematic Review.
AB  - BACKGROUND: Big data analytics offers promise in many business sectors, and
      health care is looking at big data to provide answers to many age-related issues,
      particularly dementia and chronic disease management. OBJECTIVE: The purpose of
      this review was to summarize the challenges faced by big data analytics and the
      opportunities that big data opens in health care. METHODS: A total of 3 searches
      were performed for publications between January 1, 2010 and January 1, 2016
      (PubMed/MEDLINE, CINAHL, and Google Scholar), and an assessment was made on
      content germane to big data in health care. From the results of the searches in
      research databases and Google Scholar (N=28), the authors summarized content and
      identified 9 and 14 themes under the categories Challenges and Opportunities,
      respectively. We rank-ordered and analyzed the themes based on the frequency of
      occurrence. RESULTS: The top challenges were issues of data structure, security,
      data standardization, storage and transfers, and managerial skills such as data
      governance. The top opportunities revealed were quality improvement, population
      management and health, early detection of disease, data quality, structure, and
      accessibility, improved decision making, and cost reduction. CONCLUSIONS: Big
      data analytics has the potential for positive impact and global implications;
      however, it must overcome some legitimate obstacles.

PMID- 27872038
TI  - Consent for anaesthesia-sleepwalking into trouble.

PMID- 27872037
TI  - Internet-Based Delivery of Evidence-Based Health Promotion Programs Among
      American Indian and Alaska Native Youth: A Case Study.
AB  - BACKGROUND: American Indian and Alaska Native (AI/AN) youth face multiple health
      challenges compared to other racial/ethnic groups, which could potentially be
      ameliorated by the dissemination of evidence-based adolescent health promotion
      programs. Previous studies have indicated that limited trained personnel,
      cultural barriers, and geographic isolation may hinder the reach and
      implementation of evidence-based health promotion programs among AI/AN youth.
      Although Internet access is variable in AI/AN communities across the United
      States, it is swiftly and steadily improving, and it may provide a viable
      strategy to disseminate evidence-based health promotion programs to this
      underserved population. OBJECTIVE: We explored the potential of using the
      Internet to disseminate evidence-based health promotion programs on multiple
      health topics to AI/AN youth living in diverse communities across 3
      geographically dispersed regions of the United States. Specifically, we assessed
      the Internet's potential to increase the reach and implementation of evidence
      based health promotion programs for AI/AN youth, and to engage AI/AN youth.
      METHODS: This randomized controlled trial was conducted in 25 participating sites
      in Alaska, Arizona, and the Pacific Northwest. Predominantly AI/AN youth, aged 12
      14 years, accessed 6 evidence-based health promotion programs delivered via the
      Internet, which focused on sexual health, hearing loss, alcohol use, tobacco use,
      drug use, and nutrition and physical activity. Adult site coordinators completed
      computer-based education inventory surveys, connectivity and bandwidth testing to
      assess parameters related to program reach (computer access, connectivity, and
      bandwidth), and implementation logs to assess barriers to implementation (program
      errors and delivery issues). We assessed youths' perceptions of program
      engagement via ratings on ease of use, understandability, credibility,
      likeability, perceived impact, and motivational appeal, using previously
      established measures. RESULTS: Sites had sufficient computer access and Internet
      connectivity to implement the 6 programs with adequate fidelity; however,
      variable bandwidth (ranging from 0.24 to 93.5 megabits per second; mean 25.6) and
      technical issues led some sites to access programs via back-up modalities (eg,
      uploading the programs from a Universal Serial Bus drive). The number of youth
      providing engagement ratings varied by program (n=40-191; 48-60% female, 85-90%
      self-identified AI/AN). Across programs, youth rated the programs as easy to use
      (68-91%), trustworthy (61-89%), likeable (59-87%), and impactful (63-91%). Most
      youth understood the words in the programs (60-83%), although some needed hints
      to complete the programs (16-49%). Overall, 37-66% of the participants would
      recommend the programs to a classmate, and 62-87% found the programs enjoyable
      when compared to other school lessons. CONCLUSIONS: Findings demonstrate the
      potential of the Internet to enhance the reach and implementation of evidence
      based health promotion programs, and to engage AI/AN youth. Provision of back-up
      modalities is recommended to address possible connectivity or technical issues.
      The dissemination of Internet-based health promotion programs may be a promising
      strategy to address health disparities for this underserved population. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01303575;
      https://clinicaltrials.gov/ct2/show/NCT01303575 (Archived by WebCite at
      http://www.webcitation.org/6m7DO4g7c).

PMID- 27872039
TI  - Margaret McCartney: Innovation isn't the same as evidence.

PMID- 27872040
TI  - The computer may be assessing you now, but who decided its values?

PMID- 27872041
TI  - E-cigarettes raise teens' risk of persistent cough and wheeze, study finds.

PMID- 27872042
TI  - Concerns with novel concussion protocol.

PMID- 27872043
TI  - First malaria vaccine to be tested in pilot projects, WHO announces.

PMID- 27872044
TI  - Tony Inwald.

PMID- 27872045
TI  - Pooled waiting lists and the validity of consent.

PMID- 27872046
TI  - Pituitary dysfunction after traumatic brain injury: are there definitive data in
      children?
AB  - In the past decade, several studies in adults and children have described the
      risk of pituitary dysfunction after traumatic brain injury (TBI). As a result, an
      international consensus statement recommended follow-up on the survivors. This
      paper reviews published studies regarding hypopituitarism after TBI in children
      and compares their results. The prevalence of hypopituitarism ranges from 5% to
      57%. Growth hormone (GH) and ACTH deficiency are the most common, followed by
      gonadotropins and thyroid-stimulating hormone. Paediatric studies have failed to
      identify risk factors for developing hypopituitarism, and therefore we have no
      tools to restrict screening in severe TBI. In addition, the present review
      highlights the lack of a unified follow-up and the fact that unrecognised
      pituitary dysfunction is frequent in paediatric population. The effect of
      hormonal replacement in patient recovery is important enough to consider baseline
      screening and reassessment between 6 and 12 months after TBI. Medical community
      should be aware of the risk of pituitary dysfunction in these patients, given the
      high prevalence of endocrine dysfunction already reported in the studies. Longer
      prospective studies are needed to uncover the natural course of pituitary
      dysfunction, and new studies should be designed to test the benefit of hormonal
      replacement in metabolic, cognitive and functional outcome in these patients.

PMID- 27872047
TI  - Detection of mild papilloedema in posterior uveitis using spectral domain optical
      coherence tomography.
AB  - OBJECTIVE: To compare two methods for diagnosing mild papilloedema (PO) using
      peripapillary total retinal (PTR) and retinal nerve fibre layer (RNFL) thickness
      measurement by spectral domain optical coherence tomography (OCT) in patients
      suffering from posterior uveitis. METHODS: 17 eyes in 17 patients with PO caused
      by posterior uveitis, 15 eyes in 15 patients with uveitis but with no PO based on
      slit lamp analysis were studied. High-quality OCT fundus images were analysed and
      graded by three masked observers using the Modified Frisen Scale. Eyes with PO
      were divided into two subgroups: mild (n=15) and moderate-severe PO (n=2). Two
      measurement methods were evaluated and compared: RNFL and PTR thickness
      measurements centred on the optic disc. Thickness values were calculated overall
      and for each quadrant and compared between groups. The main outcome measures were
      RNFL and PTR thickness, and thickness variation between control and affected
      patients for both protocols. RESULTS: Average RNFL and PTR thickness in the
      moderate-severe PO, mild PO and control groups were 274.5+/-54.45 um, 134+/-31.69
      um, 97.4+/-14.43 um and 722.25+/-29.34 um, 437.53+/-84.47 um, 327.8+/-25.92 um,
      respectively. Mild PO differed from the control groups according to both the RNLF
      (p=0.0006) and the PTR (p=0.0002) measurements. The average thickness variation
      between control and mild PO was significantly different between RNFL and PTR
      measurements: 36.6 um vs 109.73 um (p<0.0001), respectively. CONCLUSIONS: PTR
      thickness measurement increases the sensitivity of detection of mild PO and could
      be useful for diagnosing and monitoring papillitis. A new protocol should be
      developed to measure PTR in the same 3.5 mm disc as the RNFL measurement.

PMID- 27872048
TI  - Tolosa-Hunt syndrome and comorbidity of obsessive compulsive disorder and aortic
      aneurysm.

PMID- 27872050
TI  - Experimental, Systems, and Computational Approaches to Understanding the MicroRNA
      Mediated Reparative Potential of Cardiac Progenitor Cell-Derived Exosomes From
      Pediatric Patients.
AB  - RATIONALE: Studies have demonstrated that exosomes can repair cardiac tissue post
      myocardial infarction and recapitulate the benefits of cellular therapy.
      OBJECTIVE: We evaluated the role of donor age and hypoxia of human pediatric
      cardiac progenitor cell (CPC)-derived exosomes in a rat model of ischemia
      reperfusion injury. METHODS AND RESULTS: Human CPCs from the right atrial
      appendages from children of different ages undergoing cardiac surgery for
      congenital heart defects were isolated and cultured under hypoxic or normoxic
      conditions. Exosomes were isolated from the culture-conditioned media and
      delivered to athymic rats after ischemia-reperfusion injury. Echocardiography at
      day 3 post-myocardial infarction suggested statistically improved function in
      neonatal hypoxic and neonatal normoxic groups compared with saline-treated
      controls. At 28 days post-myocardial infarction, exosomes derived from neonatal
      normoxia, neonatal hypoxia, infant hypoxia, and child hypoxia significantly
      improved cardiac function compared with those from saline-treated controls.
      Staining showed decreased fibrosis and improved angiogenesis in hypoxic groups
      compared with controls. Finally, using sequencing data, a computational model was
      generated to link microRNA levels to specific outcomes. CONCLUSIONS: CPC exosomes
      derived from neonates improved cardiac function independent of culture oxygen
      levels, whereas CPC exosomes from older children were not reparative unless
      subjected to hypoxic conditions. Cardiac functional improvements were associated
      with increased angiogenesis, reduced fibrosis, and improved hypertrophy,
      resulting in improved cardiac function; however, mechanisms for normoxic neonatal
      CPC exosomes improved function independent of those mechanisms. This is the first
      study of its kind demonstrating that donor age and oxygen content in the
      microenvironment significantly alter the efficacy of human CPC-derived exosomes.

PMID- 27872052
TI  - Patients don't know when examination is needed.

PMID- 27872051
TI  - Management of mild hypertension in adults.
AB  - Elevated blood pressure is a common risk factor for cardiovascular disease and
      affects one in three adults. Blood pressure lowering drugs substantially reduce
      the risk of stroke, coronary heart disease, heart failure, and premature death,
      but most clinical trials showing benefits have primarily included patients with
      moderate to severe hypertension, known cardiovascular disease, or elevated risk
      of cardiovascular disease. The benefits of treating mild hypertension in patients
      without cardiovascular disease are less clear, but recent meta-analyses offer
      some insights. Pooled data from trials that include a large percentage of
      participants with mild hypertension show significant reductions in stroke, death
      from cardiovascular disease, and total mortality. Meta-analyses comparing lower
      blood pressure targets also suggest a benefit of treating patients with mild
      hypertension, although net benefits are greater for patients at higher absolute
      levels of cardiovascular disease risk. Before starting drug treatment, most
      patients should have out-of-office monitoring to confirm hypertension. Lifestyle
      modifications for reducing blood pressure are appropriate for all patients and
      may be recommended while delaying drug treatment for those at lower absolute
      levels of cardiovascular disease risk. Patient level control of blood pressure is
      supported by home monitoring and by once daily, low cost drug. Control of blood
      pressure for a population of patients is enhanced by system level interventions
      such as registries, implementation of evidence based protocols, drug titration
      visits, and performance metrics.

PMID- 27872053
TI  - The computer is still in training.

PMID- 27872049
TI  - Contribution of KV1.5 Channel to Hydrogen Peroxide-Induced Human Arteriolar
      Dilation and Its Modulation by Coronary Artery Disease.
AB  - RATIONALE: Hydrogen peroxide (H2O2) regulates vascular tone in the human
      microcirculation under physiological and pathophysiological conditions. It
      dilates arterioles by activating large-conductance Ca2+-activated K+ channels in
      subjects with coronary artery disease (CAD), but its mechanisms of action in
      subjects without CAD (non-CAD) when compared with those with CAD remain unknown.
      OBJECTIVE: We hypothesize that H2O2-elicited dilation involves different K+
      channels in non-CAD versus CAD, resulting in an altered capacity for vasodilation
      during disease. METHODS AND RESULTS: H2O2 induced endothelium-independent
      vasodilation in non-CAD adipose arterioles, which was reduced by paxilline, a
      large-conductance Ca2+-activated K+ channel blocker, and by 4-aminopyridine, a
      voltage-gated K+ (KV) channel blocker. Assays of mRNA transcripts, protein
      expression, and subcellular localization revealed that KV1.5 is the major KV1
      channel expressed in vascular smooth muscle cells and is abundantly localized on
      the plasma membrane. The selective KV1.5 blocker diphenylphosphine oxide-1 and
      the KV1.3/1.5 blocker 5-(4-phenylbutoxy)psoralen reduced H2O2-elicited dilation
      to a similar extent as 4-aminopyridine, but the selective KV1.3 blocker
      phenoxyalkoxypsoralen-1 was without effect. In arterioles from CAD subjects, H2O2
      induced dilation was significantly reduced, and this dilation was inhibited by
      paxilline but not by 4-aminopyridine, diphenylphosphine oxide-1, or 5-(4
      phenylbutoxy)psoralen. KV1.5 cell membrane localization and diphenylphosphine
      oxide-1-sensitive K+ currents were markedly reduced in isolated vascular smooth
      muscle cells from CAD arterioles, although mRNA or total cellular protein
      expression was largely unchanged. CONCLUSIONS: In human arterioles, H2O2-induced
      dilation is impaired in CAD, which is associated with a transition from a
      combined large-conductance Ca2+-activated K+- and KV (KV1.5)-mediated
      vasodilation toward a large-conductance Ca2+-activated K+-predominant mechanism
      of dilation. Loss of KV1.5 vasomotor function may play an important role in
      microvascular dysfunction in CAD or other vascular diseases.

PMID- 27872054
TI  - Final appeal seeks to block minimum alcohol price in Scotland.

PMID- 27872057
TI  - How I treat FLT3-mutated AML.
AB  - FLT3-mutated acute myeloid leukemia (AML), despite not being recognized as a
      distinct entity in the World Health Organization (WHO) classification system, is
      readily recognized as a particular challenge by clinical specialists who treat
      acute leukemia. This is especially true with regards to the patients harboring
      the most common type of FLT3 mutation, the internal tandem duplication (FLT3-ITD)
      mutation. Here we present 4 patient cases from our institution and discuss how
      our management reflects what we have learned about this subtype of the disease.
      We also reflect on how we anticipate the management might change in the near
      future, with the emergence of clinically useful tyrosine kinase inhibitors.

PMID- 27872058
TI  - A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line
      chemotherapy for FLT3-mutated AML.
AB  - The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small
      molecule therapy to standard first-line treatment of acute myeloid leukemia (AML)
      has not yet been established. As part of the UK AML15 and AML17 trials, patients
      with previously untreated AML and confirmed FLT3-activating mutations, mostly
      younger than 60 years, were randomly assigned either to receive oral lestaurtinib
      (CEP701) or not after each of 4 cycles of induction and consolidation
      chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and
      administered in cycles of up to 28 days. The trials ran consecutively. Primary
      endpoints were overall survival in AML15 and relapse-free survival in AML17;
      outcome data were meta-analyzed. Five hundred patients were randomly assigned
      between lestaurtinib and control: 74% had FLT3-internal tandem duplication
      mutations, 23% FLT3-tyrosine kinase domain point mutations, and 2% both types. No
      significant differences were seen in either 5-year overall survival (lestaurtinib
      46% vs control 45%; hazard ratio, 0.90; 95% CI 0.70-1.15; P = .3) or 5-year
      relapse-free survival (40% vs 36%; hazard ratio, 0.88; 95% CI 0.69-1.12; P = .3).
      Exploratory subgroup analysis suggested survival benefit with lestaurtinib in
      patients receiving concomitant azole antifungal prophylaxis and gemtuzumab
      ozogamicin with the first course of chemotherapy. Correlative studies included
      analysis of in vivo FLT3 inhibition by plasma inhibitory activity assay and
      indicated improved overall survival and significantly reduced rates of relapse in
      lestaurtinib-treated patients who achieved sustained greater than 85% FLT3
      inhibition. In conclusion, combining lestaurtinib with intensive chemotherapy
      proved feasible in younger patients with newly diagnosed FLT3-mutated AML, but
      yielded no overall clinical benefit. The improved clinical outcomes seen in
      patients achieving sustained FLT3 inhibition encourage continued evaluation of
      FLT3-directed therapy alongside front-line AML treatment. The UK AML15 and AML17
      trials are registered at www.isrctn.com/ISRCTN17161961 and
      www.isrctn.com/ISRCTN55675535 respectively.

PMID- 27872059
TI  - Genome-wide minor histocompatibility matching as related to the risk of graft
      versus-host disease.
AB  - The risk of acute graft-versus-host disease (GVHD) is higher after allogeneic
      hematopoietic cell transplantation (HCT) from unrelated donors as compared with
      related donors. This difference has been explained by increased recipient
      mismatching for major histocompatibility antigens or minor histocompatibility
      antigens. In the current study, we used genome-wide arrays to enumerate single
      nucleotide polymorphisms (SNPs) that produce graft-versus-host (GVH) amino acid
      coding differences between recipients and donors. We then tested the hypothesis
      that higher degrees of genome-wide recipient GVH mismatching correlate with
      higher risks of GVHD after allogeneic HCT. In HLA-genotypically matched sibling
      recipients, the average recipient mismatching of coding SNPs was 9.35%. Each 1%
      increase in genome-wide recipient mismatching was associated with an estimated
      20% increase in the hazard of grades III-IV GVHD (hazard ratio [HR], 1.20; 95%
      confidence interval [CI], 1.05-1.37; P = .007) and an estimated 22% increase in
      the hazard of stage 2-4 acute gut GVHD (HR, 1.22; 95% CI, 1.02-1.45; P = .03). In
      HLA-A, B, C, DRB1, DQA1, DQB1, DPA1, DPB1-phenotypically matched unrelated
      recipients, the average recipient mismatching of coding SNPs was 17.3%. The
      estimated risks of GVHD-related outcomes in HLA-phenotypically matched unrelated
      recipients were low, relative to the large difference in genome-wide mismatching
      between the 2 groups. In contrast, the risks of GVHD-related outcomes were higher
      in HLA-DP GVH-mismatched unrelated recipients than in HLA-matched sibling
      recipients. Taken together, these results suggest that the increased GVHD risk
      after unrelated HCT is predominantly an effect of HLA-mismatching.

PMID- 27872060
TI  - BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after
      a minimum follow-up of 6 years.
AB  - In this phase 2 multicenter trial, we evaluated the efficacy of the combination
      of bortezomib, dexamethasone, and rituximab (BDR) in 59 previously untreated
      symptomatic patients with Waldenstrom macroglobulinemia (WM), most of which were
      of advanced age and with adverse prognostic factors. BDR consisted of a single 21
      day cycle of bortezomib alone (1.3 mg/m2 IV on days 1, 4, 8, and 11), followed by
      weekly IV bortezomib (1.6 mg/m2 on days 1, 8, 15, and 22) for 4 additional 35-day
      cycles, with IV dexamethasone (40 mg) and IV rituximab (375 mg/m2) on cycles 2
      and 5, for a total treatment duration of 23 weeks. On intent to treat, 85%
      responded (3% complete response, 7% very good partial response, 58% partial
      response). After a minimum follow-up of 6 years, median progression-free survival
      was 43 months and median duration of response for patients with at least partial
      response was 64.5 months. Overall survival at 7 years was 66%. No patient had
      developed secondary myelodysplasia, whereas transformation to high-grade lymphoma
      occurred in 3 patients who had received chemoimmunotherapy after BDR. Thus, BDR
      is a very active, fixed-duration, chemotherapy-free regimen, inducing durable
      responses and with a favorable long-term toxicity profile (www.ClinicalTrials.gov
      #NCT00981708).

PMID- 27872061
TI  - Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of RG7667, a
      Combination Monoclonal Antibody, for Prevention of Cytomegalovirus Infection in
      High-Risk Kidney Transplant Recipients.
AB  - Cytomegalovirus (CMV) infection is a significant complication after kidney
      transplantation. We examined the ability of RG7667, a combination of two
      monoclonal antibodies, to prevent CMV infection in high-risk kidney transplant
      recipients in a randomized, double-blind, placebo-controlled trial. CMV
      seronegative recipients of a kidney transplant from a CMV-seropositive donor (D+R
      ) were randomized to receive RG7667 (n = 60) or placebo (n = 60) at the time of
      transplant and 1, 4, and 8 weeks posttransplant. Patients were monitored for CMV
      viremia every 1 to 2 weeks posttransplant for 24 weeks. Patients who had
      seroconverted (D+R+) or withdrawn before dosing were excluded from the analysis
      (n = 4). CMV viremia occurred in 27 of 59 (45.8%) patients receiving RG7667 and
      35 of 57 (61.4%) patients receiving placebo (stratum-adjusted difference, 15.3%;
      P = 0.100) within 12 weeks posttransplant and in 30 of 59 (50.8%) patients
      receiving RG7667 and 40 of 57 (70.2%) patients receiving placebo (stratum
      adjusted difference, 19.3%; P = 0.040) within 24 weeks posttransplant. Median
      time to CMV viremia was 139 days in patients receiving RG7667 compared to 46 days
      in patients receiving placebo (hazard ratio, 0.53; P = 0.009). CMV disease was
      less common in the RG7667 than placebo group (3.4% versus 15.8%; P = 0.030).
      Adverse events were generally balanced between treatment groups. In high-risk
      kidney transplant recipients, RG7667 was well tolerated, numerically reduced the
      incidence of CMV infection within 12 and 24 weeks posttransplant, delayed time to
      CMV viremia, and was associated with less CMV disease than the placebo. (This
      study has been registered at ClinicalTrials.gov under registration no.
      NCT01753167.).

PMID- 27872063
TI  - In Vitro Exposure to Increasing Micafungin Concentrations Easily Promotes
      Echinocandin Resistance in Candida glabrata Isolates.
AB  - We assessed the in vitro susceptibility of five echinocandin-susceptible Candida
      glabrata isolates after exposure to micafungin. The direct exposure to plates at
      different micafungin concentrations resulted in the inhibition of growth at 0.062
      MUg/ml. The progressive exposure was performed on plates using 0.031 MUg/ml of
      micafungin and sequential propagation on plates containing the next 2-fold
      concentration; the MICs of micafungin and anidulafungin increased sequentially,
      and all the isolates became echinocandin resistant, showing fks2 mutations.

PMID- 27872062
TI  - Fludioxonil Induces Drk1, a Fungal Group III Hybrid Histidine Kinase, To
      Dephosphorylate Its Downstream Target, Ypd1.
AB  - Novel antifungal drugs and targets are urgently needed. Group III hybrid
      histidine kinases (HHKs) represent an appealing new therapeutic drug target
      because they are widely expressed in fungi but absent from humans. We
      investigated the mode of action of the widely utilized, effective fungicide
      fludioxonil. The drug acts in an HHK-dependent manner by constitutive activation
      of the HOG (high-osmolarity glycerol) pathway, but its mechanism of action is
      poorly understood. Here, we report a new mode of drug action that entails
      conversion of the HHK from a kinase into a phosphatase. We expressed Drk1
      (dimorphism-regulating kinase), which is an intracellular group III HHK from the
      fungal pathogen Blastomyces dermatitidis, in Saccharomyces cerevisiae Drk1
      engendered drug sensitivity in B. dermatitidis and conferred sensitivity upon S.
      cerevisiae In response to fludioxonil, Drk1 behaved as a phosphatase rather than
      as a kinase, leading to dephosphorylation of its downstream target, Ypd1,
      constitutive activation of the HOG pathway, and yeast cell death. Aspartic acid
      residue 1140 in the Drk1 receiver domain was required for in vivo phosphatase
      activity on Ypd1, and Hog1 was required for drug effect, indicating fidelity in
      HHK-dependent drug action. In in vitro assays with purified protein, intact Drk1
      demonstrated intrinsic kinase activity, and the Drk1 receiver domain exhibited
      intrinsic phosphatase activity. However, fludioxonil failed to induce intact Drk1
      to dephosphorylate Ypd1. We conclude that fludioxonil treatment in vivo likely
      acts on an upstream target that triggers HHK to become a phosphatase, which
      dephosphorylates its downstream target, Ypd1.

PMID- 27872064
TI  - Telavancin Is Active against Experimental Aortic Valve Endocarditis Caused by
      Daptomycin- and Methicillin-Resistant Staphylococcus aureus Strains.
AB  - We compared the efficacy of telavancin (TLV) and daptomycin (DAP) in an
      experimental rabbit endocarditis model caused by two clinically derived
      daptomycin-resistant (DAPr) methicillin-resistant Staphylococcus aureus (MRSA)
      strains. TLV treatment significantly reduced MRSA densities in all target tissues
      and increased the percentage of these organs rendered culture negative compared
      to those with the untreated control or DAP-treated animals. These results
      demonstrate that TLV has potent in vivo efficacy against DAPr MRSA isolates in
      this invasive endovascular infection model.

PMID- 27872065
TI  - In Vitro Susceptibility Testing of Bedaquiline against Mycobacterium avium
      Complex.
AB  - We performed bedaquiline broth microdilution susceptibility testing using
      Clinical and Laboratory Standards Institute (CLSI) guidelines on 103 respiratory
      isolates of Mycobacterium avium complex (MAC), including multidrug-resistant
      isolates. Approximately 90% of isolates had bedaquiline MICs of <=0.008 MUg/ml,
      and 102/103 isolates had MICs of <=0.015 MUg/ml. Bedaquiline has excellent
      potential for use in patients with MAC infections, although for reasons of its
      metabolism by the cytochrome P450 system, it should not be given with rifampin.

PMID- 27872066
TI  - Clinical Characteristics and Treatment Outcomes of Patients with Macrolide
      Resistant Mycobacterium massiliense Lung Disease.
AB  - Macrolide antibiotics are cornerstones in the treatment of Mycobacterium
      massiliense lung disease. Despite the emergence of resistance, limited data on
      macrolide-resistant M massiliense lung disease are available. This study
      evaluated the clinical features and treatment outcomes of patients and the
      molecular characteristics of macrolide-resistant M massiliense isolates. We
      performed a retrospective review of medical records and genetic analyses of
      clinical isolates from 15 patients who had macrolide-resistant M massiliense lung
      disease between September 2005 and February 2015. Nine patients (60%) had the
      nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary
      form. Before the detection of macrolide resistance, three patients (20%) were
      treated with macrolide monotherapy, four (27%) with therapy for presumed
      Mycobacterium avium complex infections, and eight (53%) with combination
      antibiotic therapy for M massiliense lung disease. The median treatment duration
      after the detection of resistance was 18.7 months (interquartile range, 11.2 to
      39.8 months). Treatment outcomes were poor, with a favorable outcome being
      achieved for only one patient (7%), who underwent surgery in addition to
      antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%,
      respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at
      position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in
      macrolide resistance. Our study indicates that treatment outcomes are poor and
      mortality rates are high after the development of macrolide resistance in
      patients with M massiliense lung disease. Thus, preventing the development of
      macrolide resistance should be a key consideration during treatment.

PMID- 27872067
TI  - In Vitro Activity of Ceftazidime-Avibactam against Isolates in a Phase 3 Open
      Label Clinical Trial for Complicated Intra-Abdominal and Urinary Tract Infections
      Caused by Ceftazidime-Nonsusceptible Gram-Negative Pathogens.
AB  - The in vitro activity of ceftazidime-avibactam was evaluated against 341 Gram
      negative isolates from 333 patients in a randomized, phase 3 clinical trial of
      patients with complicated urinary tract or intra-abdominal infections caused by
      ceftazidime-nonsusceptible pathogens (NCT01644643). Ceftazidime-avibactam MIC90
      values against Enterobacteriaceae and Pseudomonas aeruginosa (including several
      class B or D enzyme producers that avibactam does not inhibit) were 1 and 64
      MUg/ml, respectively. Overall, the ceftazidime-avibactam activity against
      ceftazidime-nonsusceptible isolates was comparable to the activity of ceftazidime
      avibactam previously reported against ceftazidime-susceptible isolates. (This
      study has been registered at ClinicalTrials.gov under identifier NCT01644643.).

PMID- 27872068
TI  - Missense Mutations in the Unfoldase ClpC1 of the Caseinolytic Protease Complex
      Are Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis.
AB  - Previously, we showed that mutations in Mycobacterium tuberculosis panD, involved
      in coenzyme A biosynthesis, cause resistance against pyrazinoic acid, the
      bioactive component of the prodrug pyrazinamide. To identify additional
      resistance mechanisms, we isolated mutants resistant against pyrazinoic acid and
      subjected panD wild-type strains to whole-genome sequencing. Eight of the nine
      resistant strains harbored missense mutations in the unfoldase ClpC1 associated
      with the caseinolytic protease complex.

PMID- 27872069
TI  - Evaluation of Doravirine Pharmacokinetics When Switching from Efavirenz to
      Doravirine in Healthy Subjects.
AB  - Doravirine is a novel, potent nonnucleoside reverse transcriptase inhibitor
      (NNRTI) for the treatment of patients with human immunodeficiency virus type 1
      (HIV-1) infection that demonstrates a high genetic barrier to resistance and that
      has been well tolerated in studies to date. Doravirine is a candidate for
      patients switching from less-well-tolerated NNRTIs, such as efavirenz. While
      doravirine is a cytochrome P450 3A4 (CYP3A4) substrate, efavirenz induces CYP3A4;
      therefore, the pharmacokinetics of both drugs following a switch from efavirenz
      to doravirine were assessed. This was a 3-period, fixed-sequence, open-label
      study. Healthy adults were dosed with doravirine at 100 mg for 5 days once daily
      (QD) (period 1). Following a 7-day washout, efavirenz was administered at 600 mg
      QD for 14 days (period 2). Subsequently, doravirine was administered at 100 mg QD
      for 14 days (period 3). Blood samples were collected for pharmacokinetic
      analyses. Twenty healthy subjects were enrolled, and 17 completed the study. One
      day after efavirenz cessation, the doravirine area under the concentration-time
      curve from predosing to 24 h postdosing (AUC0-24), maximum observed plasma
      concentration (Cmax), and observed plasma concentration at 24 h postdosing (C24)
      were reduced by 62%, 35%, and 85%, respectively, compared with the values with no
      efavirenz pretreatment. These decreases recovered to 32%, 14%, and 50% for AUC0
      24, Cmax, and C24, respectively, by day 14 after efavirenz cessation. The
      doravirine C24 reached projected therapeutic trough concentrations, based on in
      vitro efficacy, on day 2 following efavirenz cessation. Geometric mean efavirenz
      concentrations were 3,180 ng/ml on day 1 and 95.7 ng/ml on day 15, and efavirenz
      was present at therapeutic concentrations (>1,000 ng/ml) until day 4. Though
      doravirine exposure was transiently decreased following efavirenz treatment
      cessation, dose adjustment may not be necessary to maintain therapeutic
      concentrations of at least one drug during switching in a virologically
      suppressed population.

PMID- 27872070
TI  - Estimation of the In Vivo MIC of Cipargamin in Uncomplicated Plasmodium
      falciparum Malaria.
AB  - The MIC of an antimalarial drug for a particular infection is the drug level
      associated with a net parasite multiplication rate of one per asexual cycle. To
      ensure the cure of malaria, the MIC must be exceeded until all parasites have
      been eliminated. The development of highly sensitive and accurate PCR
      quantitation of low-density malaria parasitemia enables the prospective
      pharmacokinetic-pharmacodynamic (PK-PD) characterization of antimalarial drug
      effects and now allows identification of the in vivo MIC. An adaptive design and
      a PK-PD modeling approach were used to determine prospectively the MIC of the new
      antimalarial cipargamin (KAE609) in adults with uncomplicated Plasmodium
      falciparum malaria in an open-label, dose-ranging phase 2a study. Vietnamese
      adults with acute P. falciparum malaria were allocated sequentially to treatment
      with a single 30-mg (n = 6), 20-mg (n = 5), 10-mg (n = 7), or 15-mg (n = 7) dose
      of cipargamin. Artemisinin-based combination therapy was given after parasite
      densities had fallen and then risen as cipargamin levels declined below the MIC
      but before a return of signs or symptoms. The rates of parasite clearance were
      dose dependent, with near saturation of the effect being seen at an adult dose of
      30 mg. The developed PK-PD model accurately predicted the therapeutic responses
      in 23/25 patients. The predicted median in vivo MIC was 0.126 ng/ml (range, 0.038
      to 0.803 ng/ml). Pharmacometric characterization of the relationship between
      antimalarial drug concentrations and parasite clearance rates following graded
      subtherapeutic antimalarial drug dosing is safe and provides a rational framework
      for dose finding in antimalarial drug development. (This study has been
      registered at ClinicalTrials.gov under identifier NCT01836458.).

PMID- 27872071
TI  - Results of a Doravirine-Atorvastatin Drug-Drug Interaction Study.
AB  - Doravirine is a novel, highly potent, nonnucleoside reverse transcriptase
      inhibitor that is administered once daily and that is in development for the
      treatment of HIV-1 infection. In vitro and clinical data suggest that doravirine
      is unlikely to cause significant drug-drug interactions via major drug
      metabolizing enzymes or transporters. As a common HIV-1 infection comorbidity,
      hypercholesterolemia is often treated with statins, including the commonly
      prescribed atorvastatin. Atorvastatin is subject to drug-drug interactions with
      cytochrome P450 3A4 (CYP3A4) inhibitors. Increased exposure due to CYP3A4
      inhibition may lead to serious adverse events (AEs), including rhabdomyolysis.
      Furthermore, atorvastatin is a substrate for breast cancer resistance protein
      (BCRP), of which doravirine may be a weak inhibitor; this may increase
      atorvastatin exposure. The potential of doravirine to affect atorvastatin
      pharmacokinetics was investigated in a two-period, fixed-sequence study in
      healthy individuals. In period 1, a single dose of atorvastatin at 20 mg was
      administered followed by a 72-h washout. In period 2, doravirine at 100 mg was
      administered once daily for 8 days, with a single dose of atorvastatin at 20 mg
      concomitantly being administered on day 5. Sixteen subjects were enrolled, and 14
      completed the trial; 2 discontinued due to AEs unrelated to the treatment. The
      atorvastatin area under the curve from time zero to infinity was similar with and
      without doravirine (geometric mean ratio [GMR] for doravirine
      atorvastatin/atorvastatin, 0.98; 90% confidence interval [CI], 0.90 to 1.06),
      while the maximum concentration decreased by 33% (GMR for doravirine
      atorvastatin/atorvastatin, 0.67; 90% CI, 0.52 to 0.85). These changes were deemed
      not to be clinically meaningful. Both of the study drugs were generally well
      tolerated. Doravirine had no clinically relevant effect on atorvastatin
      pharmacokinetics in healthy subjects, providing support for the coadministration
      of doravirine and atorvastatin.

PMID- 27872072
TI  - Pharmacokinetics of Anidulafungin in Critically Ill Intensive Care Unit Patients
      with Suspected or Proven Invasive Fungal Infections.
AB  - Echinocandins, such as anidulafungin, are the first-line treatment for candidemia
      or invasive candidiasis in critically ill patients. There are conflicting data on
      the pharmacokinetic properties of anidulafungin in intensive care unit (ICU)
      patients. Adult ICU patients (from 3 hospitals) receiving anidulafungin for
      suspected or proven fungal infections were included in the present study.
      Patients were considered evaluable if a pharmacokinetic curve for day 3 could be
      completed. Twenty-three of 36 patients (7 female and 16 male) were evaluable. The
      median (range) age and body weight were 66 (28 to 88) years and 76 (50 to 115)
      kg, respectively. Pharmacokinetic sampling on day 3 (n = 23) resulted in a median
      anidulafungin area under the concentration-time curve from 0 to 24 h (AUC0-24) of
      72.1 (interquartile range [IQR], 61.3 to 94.0) mg . h . liter-1, a median daily
      trough concentration (C24) of 2.2 (IQR, 1.9 to 2.9) mg/liter, a median maximum
      concentration of drug in serum (Cmax) of 5.3 (IQR, 4.1 to 6.0) mg/liter, a median
      volume of distribution (V) of 46.0 (IQR, 32.2 to 60.2) liters, and a median
      clearance (CL) of 1.4 (IQR, 1.1 to 1.6) liters . h-1 Pharmacokinetic sampling on
      day 7 (n = 13) resulted in a median AUC0-24 of 82.7 (IQR, 73.0 to 129.5) mg . h .
      liter-1, a median minimum concentration of drug in serum (Cmin) of 2.8 (IQR, 2.2
      to 4.2) mg/liter, a median Cmax of 5.9 (IQR, 4.6 to 8.0) mg/liter, a median V of
      39.7 (IQR, 32.2 to 54.4) liters, and a median CL of 1.2 (IQR, 0.8 to 1.4) liters
      . h-1 The geometric mean ratio for the AUCday7/AUCday3 term was 1.13 (90%
      confidence interval [CI], 1.03 to 1.25). The exposure in the ICU patient
      population was in accordance with previous reports on anidulafungin
      pharmacokinetics in ICU patients but was lower than that for healthy volunteers
      or other patient populations. Larger cohorts of patients or pooled data analyses
      are necessary to retrieve relevant covariates. (This study has been registered at
      ClinicalTrials.gov under identifier NCT01438216.).

PMID- 27872073
TI  - Exploring the Role of the Omega-Loop in the Evolution of Ceftazidime Resistance
      in the PenA beta-Lactamase from Burkholderia multivorans, an Important Cystic
      Fibrosis Pathogen.
AB  - The unwelcome evolution of resistance to the advanced generation cephalosporin
      antibiotic, ceftazidime is hindering the effective therapy of Burkholderia
      cepacia complex (BCC) infections. Regrettably, BCC organisms are highly resistant
      to most antibiotics, including polymyxins; ceftazidime and trimethoprim
      sulfamethoxazole are the most effective treatment options. Unfortunately,
      resistance to ceftazidime is increasing and posing a health threat to populations
      susceptible to BCC infection. We found that up to 36% of 146 tested BCC clinical
      isolates were nonsusceptible to ceftazidime (MICs >= 8 MUg/ml). To date, the
      biochemical basis for ceftazidime resistance in BCC is largely undefined. In this
      study, we investigated the role of the Omega-loop in mediating ceftazidime
      resistance in the PenA beta-lactamase from Burkholderia multivorans, a species
      within the BCC. Single amino acid substitutions were engineered at selected
      positions (R164, T167, L169, and D179) in the PenA beta-lactamase. Cell-based
      susceptibility testing revealed that 21 of 75 PenA variants engineered in this
      study were resistant to ceftazidime, with MICs of >8 MUg/ml. Under steady-state
      conditions, each of the selected variants (R164S, T167G, L169A, and D179N)
      demonstrated a substrate preference for ceftazidime compared to wild-type PenA
      (32- to 320-fold difference). Notably, the L169A variant hydrolyzed ceftazidime
      significantly faster than PenA and possessed an ~65-fold-lower apparent Ki
      (Kiapp) than that of PenA. To understand why these amino acid substitutions
      result in enhanced ceftazidime binding and/or turnover, we employed molecular
      dynamics simulation (MDS). The MDS suggested that the L169A variant starts with
      the most energetically favorable conformation (-28.1 kcal/mol), whereas PenA
      possessed the most unfavorable initial conformation (136.07 kcal/mol). In
      addition, we observed that the spatial arrangement of E166, N170, and the
      hydrolytic water molecules may be critical for enhanced ceftazidime hydrolysis by
      the L169A variant. Importantly, we found that two clinical isolates of B.
      multivorans possessed L169 amino acid substitutions (L169F and L169P) in PenA and
      were highly resistant to ceftazidime (MICs >= 512 MUg/ml). In conclusion,
      substitutions in the Omega-loop alter the positioning of the hydrolytic machinery
      as well as allow for a larger opening of the active site to accommodate the bulky
      R1 and R2 side chains of ceftazidime, resulting in resistance. This analysis
      provides insights into the emerging phenotype of ceftazidime-resistant BCC and
      explains the evolution of amino acid substitutions in the Omega-loop of PenA of
      this significant clinical pathogen.

PMID- 27872074
TI  - Glycoside Hydrolases Degrade Polymicrobial Bacterial Biofilms in Wounds.
AB  - The persistent nature of chronic wounds leaves them highly susceptible to
      invasion by a variety of pathogens that have the ability to construct an
      extracellular polymeric substance (EPS). This EPS makes the bacterial population,
      or biofilm, up to 1,000-fold more antibiotic tolerant than planktonic cells and
      makes wound healing extremely difficult. Thus, compounds which have the ability
      to degrade biofilms, but not host tissue components, are highly sought after for
      clinical applications. In this study, we examined the efficacy of two glycoside
      hydrolases, alpha-amylase and cellulase, which break down complex
      polysaccharides, to effectively disrupt Staphylococcus aureus and Pseudomonas
      aeruginosa monoculture and coculture biofilms. We hypothesized that glycoside
      hydrolase therapy would significantly reduce EPS biomass and convert bacteria to
      their planktonic state, leaving them more susceptible to conventional
      antimicrobials. Treatment of S. aureus and P. aeruginosa biofilms, grown in vitro
      and in vivo, with solutions of alpha-amylase and cellulase resulted in
      significant reductions in biomass, dissolution of the biofilm, and an increase in
      the effectiveness of subsequent antibiotic treatments. These data suggest that
      glycoside hydrolase therapy represents a potential safe, effective, and new
      avenue of treatment for biofilm-related infections.

PMID- 27872075
TI  - Pharmacokinetic-Pharmacodynamic Evaluation of Gepotidacin against Gram-Positive
      Organisms Using Data from Murine Infection Models.
AB  - Gepotidacin (formerly called GSK2140944) is a novel triazaacenaphthylene
      bacterial topoisomerase inhibitor with in vitro activity against conventional and
      biothreat pathogens, including Staphylococcus aureus and Streptococcus pneumoniae
      Using neutropenic murine thigh and lung infection models, the pharmacokinetics
      pharmacodynamics (PK-PD) of gepotidacin against S. aureus and S. pneumoniae were
      characterized. Candidate models were fit to single-dose PK data from uninfected
      mice (for doses of 16 to 128 mg/kg of body weight given subcutaneously [s.c.]).
      Dose fractionation studies (1 isolate/organism; 2 to 512 mg/kg/day) and dose
      ranging studies (5 isolates/organism; 2 to 2,048 mg/kg/day; MIC ranges of 0.5 to
      2 mg/liter for S. aureus and 0.125 to 1 mg/liter for S. pneumoniae) were
      conducted. The presence of an in vivo postantibiotic effect (PAE) was also
      evaluated. Relationships between the change from baseline in log10 CFU at 24 h
      and the ratio of the free-drug plasma area under the concentration-time curve
      (AUC) to the MIC (AUC/MIC ratio), the ratio of the maximum concentration of drug
      in plasma (Cmax) to the MIC (Cmax/MIC ratio), and the percentage of a 24-h period
      that the drug concentration exceeded the MIC (%T>MIC) were evaluated using Hill
      type models. Plasma and epithelial lining fluid (ELF) PK data were best fit by a
      four-compartment model with linear distributional clearances, a capacity-limited
      clearance, and a first-order absorption rate. The ELF penetration ratio in
      uninfected mice was 0.65. Since the growth of both organisms was poor in the
      murine lung infection model, lung efficacy data were not reported. As determined
      using the murine thigh infection model, the free-drug plasma AUC/MIC ratio was
      the PK-PD index most closely associated with efficacy (r2 = 0.936 and 0.897 for
      S. aureus and S. pneumoniae, respectively). Median free-drug plasma AUC/MIC
      ratios of 13.4 and 58.9 for S. aureus, and 7.86 and 16.9 for S. pneumoniae, were
      associated with net bacterial stasis and a 1-log10 CFU reduction from baseline,
      respectively. Dose-independent PAE durations of 3.07 to 12.5 h and 5.25 to 8.46 h
      were demonstrated for S. aureus and S. pneumoniae, respectively.

PMID- 27872076
TI  - Antischistosomiasis Liver Fibrosis Effects of Chlorogenic Acid through IL-13/miR
      21/Smad7 Signaling Interactions In Vivo and In Vitro.
AB  - This study investigated the antischistosomiasis liver fibrosis effects of
      chlorogenic acid (CGA) on interleukin 13 (IL-13)/microRNA-21 (miR-21)/Smad7
      signaling interactions in the hepatic stellate LX2 cell line and schistosome
      infected mice. The transfection was based on the ability of the GV273-miR-21
      enhanced green fluorescent protein (EGFP) and GV369-miR-21-EGFP lentiviral system
      to up- or downregulate the miR-21 gene in LX2 cells. The mRNA expression of miR
      21, Smad7, and connective tissue growth factor (CTGF) and the protein expression
      of Smad7, CTGF, Smad1, phosphor-Smad1 (p-Smad1), Smad2, p-Smad2, Smad2/3, p
      Smad2/3, transforming growth factor beta (TGF-beta) receptor I, and alpha-smooth
      muscle actin (alpha-SMA) was assayed. Pathological manifestation of hepatic
      tissue was assessed for the degree of liver fibrosis in animals. The results
      showed that CGA could inhibit the mRNA expression of miR-21, promote Smad7, and
      inhibit CTGF mRNA expression. Meanwhile, CGA could significantly lower the
      protein levels of CTGF, p-Smad1, p-Smad2, p-Smad2/3, TGF-beta receptor I, and
      alpha-SMA and elevate the Smad7 protein level. In vivo, with treatment with CGA,
      the signaling molecules of IL-13/miR-21/Smad7 interactions were markedly
      regulated. CGA could also reduce the degree of liver fibrosis in pathological
      manifestations. In conclusion, CGA could inhibit schistosomiasis-induced hepatic
      fibrosis through IL-13/miR-21/Smad7 signaling interactions in LX2 cells and
      schistosome-infected mice and might serve as an antifibrosis agent for treating
      schistosomiasis liver fibrosis.

PMID- 27872077
TI  - Identification of IncA/C Plasmid Replication and Maintenance Genes and
      Development of a Plasmid Multilocus Sequence Typing Scheme.
AB  - Plasmids of incompatibility group A/C (IncA/C) are becoming increasingly
      prevalent within pathogenic Enterobacteriaceae They are associated with the
      dissemination of multiple clinically relevant resistance genes, including blaCMY
      and blaNDM Current typing methods for IncA/C plasmids offer limited resolution.
      In this study, we present the complete sequence of a blaNDM-1-positive IncA/C
      plasmid, pMS6198A, isolated from a multidrug-resistant uropathogenic Escherichia
      coli strain. Hypersaturated transposon mutagenesis, coupled with transposon
      directed insertion site sequencing (TraDIS), was employed to identify conserved
      genetic elements required for replication and maintenance of pMS6198A. Our
      analysis of TraDIS data identified roles for the replicon, including repA, a
      toxin-antitoxin system; two putative partitioning genes, parAB; and a putative
      gene, 053 Construction of mini-IncA/C plasmids and examination of their stability
      within E. coli confirmed that the region encompassing 053 contributes to the
      stable maintenance of IncA/C plasmids. Subsequently, the four major maintenance
      genes (repA, parAB, and 053) were used to construct a new plasmid multilocus
      sequence typing (PMLST) scheme for IncA/C plasmids. Application of this scheme to
      a database of 82 IncA/C plasmids identified 11 unique sequence types (STs), with
      two dominant STs. The majority of blaNDM-positive plasmids examined (15/17; 88%)
      fall into ST1, suggesting acquisition and subsequent expansion of this blaNDM
      containing plasmid lineage. The IncA/C PMLST scheme represents a standardized
      tool to identify, track, and analyze the dissemination of important IncA/C
      plasmid lineages, particularly in the context of epidemiological studies.

PMID- 27872078
TI  - Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B
      Resistant KPC-Producing Klebsiella pneumoniae.
AB  - Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC
      producing Klebsiella pneumoniae infections and suppress the emergence of
      resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and
      meropenem alone and as polymyxin B-based double and triple combinations against
      KPC-producing K. pneumoniae isolates. The rates and extents of killing with
      polymyxin B (1 to 128 mg/liter), rifampin (2 to 16 mg/liter), and meropenem (10
      to 120 mg/liter) were evaluated against polymyxin B-susceptible (PBs) and
      polymyxin B-resistant (PBr) clinical isolates using 48-h static time-kill
      studies. Additionally, humanized triple-drug regimens of polymyxin B
      (concentration at steady state [Css] values of 0.5, 1, and 2 mg/liter), 600 mg
      rifampin every 12 or 8 h, and 1 or 2 g meropenem every 8 h dosed as an extended 3
      h infusion were simulated over 48 h by using a one-compartment in vitro dynamic
      infection model. Serial bacterial counts were performed to quantify the
      pharmacodynamic effect. Population analysis profiles (PAPs) were used to assess
      the emergence of polymyxin B resistance. Monotherapy was ineffective against both
      isolates. Polymyxin B with rifampin demonstrated early bactericidal activity
      against the PBs isolate, followed by regrowth by 48 h. Bactericidal activity was
      sustained at all polymyxin B concentrations of >=2 mg/liter in combination with
      meropenem. No two-drug combinations were effective against the PBr isolate, but
      all simulated triple-drug regimens showed early bactericidal activity against
      both strains by 8 h that was sustained over 48 h. PAPs did not reveal the
      emergence of resistant subpopulations. The triple-drug combination of polymyxin
      B, rifampin, and meropenem may be a viable consideration for the treatment of PBr
      KPC-producing K. pneumoniae infections. Further investigation is warranted to
      optimize triple-combination therapy.

PMID- 27872079
TI  - The Paradoxical Effect of Echinocandins in Aspergillus fumigatus Relies on
      Recovery of the beta-1,3-Glucan Synthase Fks1.
AB  - Echinocandins target the fungal cell wall by inhibiting biosynthesis of the cell
      wall carbohydrate beta-1,3-glucan. This antifungal drug class exhibits a
      paradoxical effect that is characterized by the resumption of growth of otherwise
      susceptible strains at higher drug concentrations (approximately 4 to 32 MUg/ml).
      The nature of this phenomenon is still unknown. In this study, we analyzed the
      paradoxical effect of the echinocandin caspofungin on the pathogenic mold
      Aspergillus fumigatus Using a conditional fks1 mutant, we show that very high
      caspofungin concentrations exert an additional antifungal activity besides
      inhibition of the beta-1,3-glucan synthase. This activity could explain the
      suppression of paradoxical growth at very high caspofungin concentrations.
      Additionally, we found that exposure to inhibitory caspofungin concentrations
      always causes initial growth deprivation independently of the capability of the
      drug concentration to induce the paradoxical effect. Paradoxically growing hyphae
      emerge from microcolonies essentially devoid of beta-1,3-glucan. However, these
      hyphae expose beta-1,3-glucan again, suggesting that beta-1,3-glucan synthesis is
      restored. In agreement with this hypothesis, we found that expression of the beta
      1,3-glucan synthase Fks1 is an essential requirement for the paradoxical effect.
      Surprisingly, overexpression of fks1 renders A. fumigatus more susceptible,
      whereas reduced expression leads to hyphae that are more resistant to the growth
      inhibitory and limited fungicidal activity of caspofungin. Upregulation of chitin
      synthesis appears to be of minor importance for the paradoxical effect, since
      paradoxically growing hyphae exhibit significantly less chitin than the growth
      deprived parental microcolonies. Our results argue for a model where the
      paradoxical effect primarily relies on recovery of beta-1,3-glucan synthase
      activity.

PMID- 27872082
TI  - Evolving Use of Natriuretic Peptides as Part of Strategies for Heart Failure
      Prevention.
AB  - BACKGROUND: Heart failure (HF) remains one of the major cardiovascular challenges
      to the Western world. Once established, HF is characterized by compromised life
      expectancy and quality of life with considerable dependence on hospital care for
      episodic clinical deterioration. Much is understood about the risk factors that
      predispose to the development of HF. With such a broad range of factors, it is
      clear that there is a large population at risk, potentially in excess of 25% of
      the adult population. Therein lies the major challenge at the outset of our
      efforts to prevent HF. With such a large population at risk, how do we develop an
      effective prevention strategy? CONTENT: HF prevention requires a multimodal
      approach. In this review, we focus primarily on the role of natriuretic peptide
      (NP) as a tool in a prevention strategy. SUMMARY: Prevention of HF is a major
      public health challenge, underlined by the concerning epidemiological trends, the
      associated costs, and the continued difficulty to find effective therapies for
      the growing number of patients with preserved systolic function HF. Population
      based approaches focusing on lifestyle and risk factor control have made some
      impact but not to a satisfactory level and also tend to result in a uniform
      approach across a population with different risk profiles. Individualizing risk
      is therefore required, with emerging data indicating that NP-guided risk
      stratification and intervention can reduce downstream incident HF and other
      cardiovascular events.

PMID- 27872080
TI  - Classical beta-Lactamase Inhibitors Potentiate the Activity of Daptomycin against
      Methicillin-Resistant Staphylococcus aureus and Colistin against Acinetobacter
      baumannii.
AB  - We asked whether beta-lactamase inhibitors (BLIs) increased the activity of
      daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), the
      peptide antibiotic colistin (COL) against the emerging Gram-negative nosocomial
      pathogen Acinetobacter baumannii, and the human host defense peptide cathelicidin
      LL37 against either pathogen. DAP and LL37 kill curves were performed with or
      without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA), and
      heterogeneous VISA (hVISA). COL and LL37 kill curves were performed against A.
      baumannii Boron-dipyrromethene (BODIPY)-labeled DAP binding to MRSA grown with
      the BLI tazobactam (TAZ) was assessed microscopically. The combination of COL
      plus TAZ was studied in a murine model of A. baumannii pneumonia. TAZ alone
      lacked in vitro activity against MRSA or A. baumannii The addition of TAZ to DAP
      resulted in a 2- to 5-log10 reduction in recoverable MRSA CFU at 24 h compared to
      the recoverable CFU with DAP alone. TAZ plus COL showed synergy by kill curves
      for 4 of 5 strains of A. baumannii tested. Growth with 20 mg/liter TAZ resulted
      in 2- to 2.5-fold increases in the intensity of BODIPY-DAP binding to MRSA and
      hVISA strains. TAZ significantly increased the killing of MRSA and A. baumannii
      by LL37 in vitro TAZ increased the activity of COL in a murine model of A.
      baumannii pneumonia. Classical BLIs demonstrate synergy with peptide antibiotics.
      Since BLIs have scant antimicrobial activity on their own and are thus not
      expected to increase selective pressure toward antibiotic resistance, their use
      in combination with peptide antibiotics warrants further study.

PMID- 27872081
TI  - Novel Effects of Lapatinib Revealed in the African Trypanosome by Using
      Hypothesis-Generating Proteomics and Chemical Biology Strategies.
AB  - Human African trypanosomiasis is a neglected tropical disease caused by the
      protozoan parasite Trypanosoma brucei Lapatinib, a human epidermal growth factor
      receptor (EGFR) inhibitor, can cure 25% of trypanosome-infected mice, although
      the parasite lacks EGFR-like tyrosine kinases. Four trypanosome protein kinases
      associate with lapatinib, suggesting that the drug may be a multitargeted
      inhibitor of phosphoprotein signaling in the bloodstream trypanosome.
      Phosphoprotein signaling pathways in T. brucei have diverged significantly from
      those in humans. As a first step in the evaluation of the polypharmacology of
      lapatinib in T. brucei, we performed a proteome-wide phosphopeptide analysis
      before and after drug addition to cells. Lapatinib caused dephosphorylation of
      Ser/Thr sites on proteins predicted to be involved in scaffolding, gene
      expression, and intracellular vesicle trafficking. To explore the perturbation of
      phosphotyrosine (pTyr)-dependent signaling by lapatinib, proteins in lapatinib
      susceptible pTyr complexes were identified by affinity chromatography; they
      included BILBO-1, MORN, and paraflagellar rod (PFR) proteins PFR1 and PFR2. These
      data led us to hypothesize that lapatinib disrupts PFR functions and/or
      endocytosis in the trypanosome. In direct chemical biology tests of these
      speculations, lapatinib-treated trypanosomes (i) lost segments of the PFR inside
      the flagellum, (ii) were inhibited in the endocytosis of transferrin, and (iii)
      changed morphology from long and slender to rounded. Thus, our hypothesis
      generating phosphoproteomics strategy predicted novel physiological pathways
      perturbed by lapatinib, which were verified experimentally. General implications
      of this workflow for identifying signaling pathways perturbed by drug hits
      discovered in phenotypic screens are discussed.

PMID- 27872084
TI  - Patient perspectives on delays in diagnosis and treatment of cancer: a
      qualitative analysis of free-text data.
AB  - BACKGROUND: Earlier cancer diagnosis is crucial in improving cancer survival. The
      International Cancer Benchmarking Partnership Module 4 (ICBP4) is a quantitative
      survey study that explores the reasons for delays in diagnosis and treatment of
      breast, colorectal, lung, and ovarian cancer. To further understand the
      associated diagnostic processes, it is also important to explore the patient
      perspectives expressed in the free-text comments. AIM: To use the free-text data
      provided by patients completing the ICBP4 survey to augment the understanding of
      patients' perspectives of their diagnostic journey. DESIGN AND SETTING:
      Qualitative analysis of the free-text data collected in Wales between October
      2013 and December 2014 as part of the ICBP4 survey. Newly-diagnosed patients with
      either breast, ovarian, colorectal, or lung cancer were identified from registry
      data and then invited by their GPs to participate in the survey. METHOD: A
      thematic framework was used to analyse the free-text comments provided at the end
      of the ICBP4 survey. Of the 905 patients who returned a questionnaire, 530
      included comments. RESULTS: The free-text data provided information about
      patients' perspectives of the diagnostic journey. Analysis identified factors
      that acted as either barriers or facilitators at different stages of the
      diagnostic process. Some factors, such as screening, doctor-patient familiarity,
      and private treatment, acted as both barriers and facilitators depending on the
      context. CONCLUSION: Factors identified in this study help to explain how
      existing models of cancer diagnosis (for example, the Pathways to Treatment
      Model) work in practice. It is important that clinicians are aware of how these
      factors may interact with individual clinical cases and either facilitate, or act
      as a barrier to, subsequent cancer diagnosis. Understanding and implementing this
      knowledge into clinical practice may result in quicker cancer diagnoses.

PMID- 27872083
TI  - Biomarkers and Genetics in Peripheral Artery Disease.
AB  - BACKGROUND: Peripheral artery disease (PAD) is highly prevalent and there is
      considerable diversity in the initial clinical manifestation and disease
      progression among individuals. Currently, there is no ideal biomarker to screen
      for PAD, to risk stratify patients with PAD, or to monitor therapeutic response
      to revascularization procedures. Advances in human genetics have markedly
      enhanced the ability to develop novel diagnostic and therapeutic approaches
      across a host of human diseases, but such developments in the field of PAD are
      lagging. CONTENT: In this article, we will discuss the epidemiology, traditional
      risk factors for, and clinical presentations of PAD. We will discuss the possible
      role of genetic factors and gene-environment interactions in the development
      and/or progression of PAD. We will further explore future avenues through which
      genetic advances can be used to better our understanding of the pathophysiology
      of PAD and potentially find newer therapeutic targets. We will discuss the
      potential role of biomarkers in identifying patients at risk for PAD and for risk
      stratifying patients with PAD, and novel approaches to identification of reliable
      biomarkers in PAD. SUMMARY: The exponential growth of genetic tools and newer
      technologies provides opportunities to investigate and identify newer pathways in
      the development and progression of PAD, and thereby in the identification of
      newer biomarkers and therapies.

PMID- 27872085
TI  - Population health needs as predictors of variations in NHS practice payments: a
      cross-sectional study of English general practices in 2013-2014 and 2014-2015.
AB  - BACKGROUND: NHS general practice payments in England include pay for performance
      elements and a weighted component designed to compensate for workload, but
      without measures of specific deprivation or ethnic groups. AIM: To determine
      whether population factors related to health needs predicted variations in NHS
      payments to individual general practices in England. DESIGN AND SETTING: Cross
      sectional study of all practices in England, in financial years 2013-2014 and
      2014-2015. METHOD: Descriptive statistics, univariable analyses (examining
      correlations between payment and predictors), and multivariable analyses
      (undertaking multivariable linear regressions for each year, with logarithms of
      payments as the dependent variables, and with population, practice, and
      performance factors as independent variables) were undertaken. RESULTS: Several
      population variables predicted variations in adjusted total payments, but
      inconsistently. Higher payments were associated with increases in deprivation,
      patients of older age, African Caribbean ethnic group, and asthma prevalence.
      Lower payments were associated with an increase in smoking prevalence. Long-term
      health conditions, South Asian ethnic group, and diabetes prevalence were not
      predictive. The adjusted R2 values were 0.359 (2013-2014) and 0.374 (2014-2015).
      A slightly different set of variables predicted variations in the payment
      component designed to compensate for workload. Lower payments were associated
      with increases in deprivation, patients of older age, and diabetes prevalence.
      Smoking prevalence was not predictive. There was a geographical differential.
      CONCLUSION: Population factors related to health needs were, overall, poor
      predictors of variations in adjusted total practice payments and in the payment
      component designed to compensate for workload. Revising the weighting formula and
      extending weighting to other payment components might better support practices to
      address these needs.

PMID- 27872086
TI  - Intensive care discharge summaries for general practice staff: a focus group
      study.
AB  - BACKGROUND: Understanding how patients and relatives can be supported after
      hospital discharge is a UK research priority. Intensive Care Unit (ICU) discharge
      summaries are a simple way of providing GPs with the information they require to
      coordinate ongoing care, but little evidence is available to guide best practice.
      AIM: This study aimed at better understanding the information needs of GP staff
      (GPs and practice nurses) supporting former patients of ICUs and their families
      following discharge from hospital, and identifying the barriers/facilitators
      associated with ICU-primary care information transfer. DESIGN AND SETTING: This
      was a qualitative exploratory study of practices and participants throughout the
      UK. METHOD: Audiotaped focus group discussions, complemented by small
      group/individual interviews, were conducted with 15 former patients of ICUs, four
      relatives, and 20 GP staff between June and September 2015. Demographic data were
      captured by questionnaire and qualitative data were thematically analysed.
      RESULTS: Findings suggest variability in discharge information experiences and
      blurred lines of responsibility between hospital and GP staff, and
      patients/relatives. Continuity of care was affected by delayed or poor
      communication from the hospital; GPs' limited contact with patients from critical
      care; and a lack of knowledge of the effects of critical illness or resources
      available to ameliorate these difficulties. Time pressures and information
      technology were, respectively, the most commonly mentioned barrier and
      facilitator. CONCLUSION: Effective rehabilitation after a critical illness
      requires a coordinated and comprehensive approach, incorporating the provision of
      well-completed, timely, and relevant ICU-primary care discharge information.
      Health professionals need an improved understanding of critical illness, and
      patients and families must be included in all aspects of the information-sharing
      process.

PMID- 27872087
TI  - Tim-3 Expression on Tumor-Infiltrating PD-1+CD8+ T Cells Correlates with Poor
      Clinical Outcome in Renal Cell Carcinoma.
AB  - Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens,
      with coexpression of these receptors exacerbating this dysfunctional state. Using
      the VectraR automated multiparametric immunofluorescence technique, we quantified
      intratumoral CD8+ T cells coexpressing the inhibitory receptors PD-1 and Tim-3
      from patients with renal cell carcinoma (RCC). A second validation cohort
      measured the same parameters by cytometry. The percentage of tumor-infiltrating
      CD8+ T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype
      and a larger tumor size at diagnosis. Coexpression of PD-1 and Tim-3 above the
      median conferred a higher risk of relapse and a poorer 36-month overall survival.
      Notably, other CD8+T-cell subsets did not exert a similar effect on overall
      survival. Moreover, only the PD-1+Tim-3+ subset of CD8+ T cells exhibited
      impaired function after stimulation. Our findings establish intratumoral Tim
      3+PD1+CD8+ T cells as critical mediators of an aggressive phenotype in RCC. Use
      of the Vectra tool may be useful to identify similarly critical prognostic and
      predictive biomarkers in other tumor types and their response to immunotherapy.
      Cancer Res; 77(5); 1075-82. (c)2016 AACR.

PMID- 27872088
TI  - H-Ras and K-Ras Oncoproteins Induce Different Tumor Spectra When Driven by the
      Same Regulatory Sequences.
AB  - Genetic studies in mice have provided evidence that H-Ras and K-Ras proteins are
      bioequivalent. However, human tumors display marked differences in the
      association of RAS oncogenes with tumor type. Thus, to further assess the
      bioequivalence of oncogenic H-Ras and K-Ras, we replaced the coding region of the
      murine K-Ras locus with H-RasG12V oncogene sequences. Germline expression of H
      RasG12V or K-RasG12V from the K-Ras locus resulted in embryonic lethality.
      However, expression of these genes in adult mice led to different tumor
      phenotypes. Whereas H-RasG12V elicited papillomas and hematopoietic tumors, K
      RasG12V induced lung tumors and gastric lesions. Pulmonary expression of H
      RasG12V created a senescence-like state caused by excessive MAPK signaling.
      Likewise, H-RasG12V but not K-RasG12V induced senescence in mouse embryonic
      fibroblasts. Label-free quantitative analysis revealed that minor differences in
      H-RasG12V expression levels led to drastically different biological outputs,
      suggesting that subtle differences in MAPK signaling confer nonequivalent
      functions that influence tumor spectra induced by RAS oncoproteins. Cancer Res;
      77(3); 707-18. (c)2016 AACR.

PMID- 27872089
TI  - Transcriptional Induction of Periostin by a Sulfatase 2-TGFbeta1-SMAD Signaling
      Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma.
AB  - Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma
      (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this
      disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving
      HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to
      diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice
      (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice
      exhibited a markedly lower microvascular density. In human HCC cells, SULF2
      overexpression increased endothelial proliferation, adhesion, chemotaxis, and
      tube formation in a paracrine fashion. Mechanistic analyses identified the
      extracellular matrix protein periostin (POSTN), a ligand of alphavbeta3/5
      integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing
      in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo The
      TGFbeta1/SMAD pathway was identified as a critical signaling axis between SULF2
      and upregulation of POSTN transcription. In clinical HCC specimens, elevated
      levels of SULF2 correlated with increased microvascular density, POSTN levels,
      and relatively poorer patient survival. Together, our findings define an
      important axis controlling angiogenesis in HCC and a mechanistic foundation for
      rational drug development. Cancer Res; 77(3); 632-45. (c)2016 AACR.

PMID- 27872091
TI  - Macrophage-Secreted TNFalpha and TGFbeta1 Influence Migration Speed and
      Persistence of Cancer Cells in 3D Tissue Culture via Independent Pathways.
AB  - The ability of a cancer cell to migrate through the dense extracellular matrix
      within and surrounding the solid tumor is a critical determinant of metastasis.
      Macrophages enhance invasion and metastasis in the tumor microenvironment, but
      the basis for their effects is not fully understood. Using a microfluidic 3D cell
      migration assay, we found that the presence of macrophages enhanced the speed and
      persistence of cancer cell migration through a 3D extracellular matrix in a
      matrix metalloproteinases (MMP)-dependent fashion. Mechanistic investigations
      revealed that macrophage-released TNFalpha and TGFbeta1 mediated the observed
      behaviors by two distinct pathways. These factors synergistically enhanced
      migration persistence through a synergistic induction of NF-kappaB-dependent MMP1
      expression in cancer cells. In contrast, macrophage-released TGFbeta1 enhanced
      migration speed primarily by inducing MT1-MMP expression. Taken together, our
      results reveal new insights into how macrophages enhance cancer cell metastasis,
      and they identify TNFalpha and TGFbeta1 dual blockade as an antimetastatic
      strategy in solid tumors. Cancer Res; 77(2); 279-90. (c)2016 AACR.

PMID- 27872092
TI  - Plk4 Promotes Cancer Invasion and Metastasis through Arp2/3 Complex Regulation of
      the Actin Cytoskeleton.
AB  - The polo family serine threonine kinase Plk4 has been proposed as a therapeutic
      target in advanced cancers based on increased expression in primary human
      cancers, facilitation of tumor growth in murine xenograft models, and centrosomal
      amplification induced by its overexpression. However, both the causal link
      between these phenomena and the feasibility of selective Plk4 inhibition remain
      unclear. Here we characterize Plk4-dependent cancer cell migration and invasion
      as well as local invasion and metastasis of cancer xenografts. Plk4 depletion
      suppressed cancer invasion and induced an epithelial phenotype in poorly
      differentiated breast cancer cells. In an unbiased BioID screen for Plk4
      interactors, we identified members of the Arp2/3 complex and confirmed a physical
      and functional interaction between Plk4 and Arp2 in mediating Plk4-driven cancer
      cell movement. This interaction is mediated through the Plk4 Polo-box 1-Polo-box
      2 domain and results in phosphorylation of Arp2 at the T237/T238 activation site,
      which is required for Plk4-driven cell movement. Our results validate Plk4 as a
      therapeutic target in cancer patients and reveal a new role for Plk4 in
      regulating Arp2/3-mediated actin cytoskeletal rearrangement. Cancer Res; 77(2);
      434-47. (c)2016 AACR.

PMID- 27872090
TI  - Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia.
AB  - Current standard of care for patients with pediatric acute lymphoblastic leukemia
      (ALL) is mainly effective, with high remission rates after treatment. However,
      the genetic perturbations that give rise to this disease remain largely
      undefined, limiting the ability to address resistant tumors or develop less toxic
      targeted therapies. Here, we report the use of next-generation sequencing to
      interrogate the genetic and pathogenic mechanisms of 240 pediatric ALL cases with
      their matched remission samples. Commonly mutated genes fell into several
      categories, including RAS/receptor tyrosine kinases, epigenetic regulators,
      transcription factors involved in lineage commitment, and the p53/cell-cycle
      pathway. Unique recurrent mutational hotspots were observed in epigenetic
      regulators CREBBP (R1446C/H), WHSC1 (E1099K), and the tyrosine kinase FLT3
      (K663R, N676K). The mutant WHSC1 was established as a gain-of-function oncogene,
      while the epigenetic regulator ARID1A and transcription factor CTCF were
      functionally identified as potential tumor suppressors. Analysis of 28
      diagnosis/relapse trio patients plus 10 relapse cases revealed four evolutionary
      paths and uncovered the ordering of acquisition of mutations in these patients.
      This study provides a detailed mutational portrait of pediatric ALL and gives
      insights into the molecular pathogenesis of this disease. Cancer Res; 77(2); 390
      400. (c)2016 AACR.

PMID- 27872094
TI  - MIF-Induced Stromal PKCbeta/IL8 Is Essential in Human Acute Myeloid Leukemia.
AB  - Acute myeloid leukemia (AML) cells exhibit a high level of spontaneous apoptosis
      when cultured in vitro but have a prolonged survival time in vivo, indicating
      that tissue microenvironment plays a critical role in promoting AML cell
      survival. In vitro studies have shown that bone marrow mesenchymal stromal cells
      (BM-MSC) protect AML blasts from spontaneous and chemotherapy-induced apoptosis.
      Here, we report a novel interaction between AML blasts and BM-MSCs, which
      benefits AML proliferation and survival. We initially examined the cytokine
      profile in cultured human AML compared with AML cultured with BM-MSCs and found
      that macrophage migration inhibitory factor (MIF) was highly expressed by primary
      AML, and that IL8 was increased in AML/BM-MSC cocultures. Recombinant MIF
      increased IL8 expression in BM-MSCs via its receptor CD74. Moreover, the MIF
      inhibitor ISO-1 inhibited AML-induced IL8 expression by BM-MSCs as well as BM-MSC
      induced AML survival. Protein kinase C beta (PKCbeta) regulated MIF-induced IL8
      in BM-MSCs. Finally, targeted IL8 shRNA inhibited BM-MSC-induced AML survival.
      These results describe a novel, bidirectional, prosurvival mechanism between AML
      blasts and BM-MSCs. Furthermore, they provide biologic rationale for therapeutic
      strategies in AML targeting the microenvironment, specifically MIF and IL8.
      Cancer Res; 77(2); 303-11. (c)2016 AACR.

PMID- 27872093
TI  - A Novel Platinum(II)-Based Bifunctional ADC Linker Benchmarked Using 89Zr
      Desferal and Auristatin F-Conjugated Trastuzumab.
AB  - Greater control is desirable in the stochastic conjugation technology used to
      synthesize antibody-drug conjugates (ADC). We have shown recently that a
      fluorescent dye can be stably conjugated to a mAb using a bifunctional
      platinum(II) linker. Here, we describe the general applicability of this novel
      linker technology for the preparation of stable and efficacious ADCs. The
      ethylenediamine platinum(II) moiety, herein called Lx, was coordinated to
      Desferal (DFO) or auristatin F (AF) to provide storable "semifinal" products,
      which were directly conjugated to unmodified mAbs. Conjugation resulted in ADCs
      with unimpaired mAb-binding characteristics, DAR in the range of 2.5 to 2.7 and
      approximately 85% payload bound to the Fc region, presumably to histidine
      residues. To evaluate the in vivo stability of Lx and its effect on
      pharmacokinetics and tumor targeting of an ADC, Lx-DFO was conjugated to the HER2
      mAb trastuzumab, followed by radiolabeling with 89Zr. Trastuzumab-Lx-DFO-89Zr was
      stable in vivo and exhibited pharmacokinetic and tumor-targeting properties
      similar to parental trastuzumab. In a xenograft mouse model of gastric cancer
      (NCI-N87) or an ado-trastuzumab emtansine-resistant breast cancer (JIMT-1), a
      single dose of trastuzumab-Lx-AF outperformed its maleimide benchmark trastuzumab
      Mal-AF and FDA-approved ado-trastuzumab emtansine. Overall, our findings show the
      potential of the Lx technology as a robust conjugation platform for the
      preparation of anticancer ADCs. Cancer Res; 77(2); 257-67. (c)2016 AACR.

PMID- 27872095
TI  - T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral
      TNFalpha Expression and Empower Adoptive Cell Therapy for Solid Tumors.
AB  - Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects
      likely due to the simultaneous recognition of tumor-specific and host-restricted
      minor histocompatibility (H) antigens. Here we investigated whether such effects
      could be reproduced in autologous settings by TCR gene-engineered lymphocytes. We
      report that T cells redirected either to a broadly expressed Y-encoded minor H
      antigen or to a tumor-associated antigen, although poorly effective if
      individually transferred, when simultaneously administered enabled acute
      autochthonous tumor debulking and resulted in durable clinical remission. Y
      redirected T cells proved hyporesponsive in peripheral lymphoid organs, whereas
      they retained effector function at the tumor site, where in synergy with tumor
      redirected lymphocytes, they instructed TNFalpha expression, endothelial cell
      activation, and intratumoral T-cell infiltration. While neutralizing TNFalpha
      hindered GVT effects by the combined T-cell infusion, a single injection of
      picogram amounts of NGR-TNF, a tumor vessel-targeted TNFalpha derivative
      currently in phase III clinical trials, substituted for Y-redirected cells and
      enabled tumor debulking by tumor-redirected lymphocytes. Together, our results
      provide new mechanistic insights into allogeneic GVT, validate the importance of
      targeting the tumor and its associated stroma, and prove the potency of a novel
      combined approach suitable for immediate clinical implementation. Cancer Res;
      77(3); 658-71. (c)2016 AACR.

PMID- 27872096
TI  - PolyI:C and CpG Synergize with Anti-ErbB2 mAb for Treatment of Breast Tumors
      Resistant to Immune Checkpoint Inhibitors.
AB  - Innate and adaptive immune cells play an important role in the therapeutic
      activity of anti-ErbB2 mAbs, such as trastuzumab. In the clinic, breast tumors
      poorly infiltrated with immune cells are more resistant to trastuzumab, and
      patients have a worse prognosis. Because type I and II IFNs are critical to the
      immune-mediated activity of anti-ErbB2 mAb, we investigated the effect of
      combining polyI:C and CpG with trastuzumab-like therapy in immunocompetent mouse
      models of ErbB2+ breast cancer. We demonstrated that in situ delivery of polyI:C
      and CpG combined to systemic anti-ErbB2 mAb triggered a potent inflammatory
      response in breast tumors able to induce long-lasting CD8+ T cell-dependent
      antitumor immunity. Remarkably, polyI:C and CpG was superior to combined PD
      1/CTLA-4 blockade in sensitizing tumors to anti-ErbB2 mAb therapy. Local
      injection of CpG and polyI:C in a primary tumor significantly enhanced the
      activity of systemic anti-ErbB2 mAb against a distant untreated tumor. Type I and
      II IFNs, as well as natural killer cells and CD8+ T cells, were indispensible to
      the synergistic activity of the combination treatment. Because synthetic RNA
      analogues and CpG oligodeoxynucleotides have been safely used in clinical trials,
      our study supports combination treatments with anti-ErbB2 mAbs. Cancer Res;
      77(2); 312-9. (c)2016 AACR.

PMID- 27872099
TI  - Conflicting Signals for Cancer Treatment.
AB  - Next-generation sequencing technologies have provided us with a precise
      description of the mutational burden of cancers, making it possible to identify
      targetable oncogene addictions. However, the emergence of resistant clones is an
      inevitable limitation of therapies targeting these addictions. Alternative
      approaches to cancer treatment are therefore required. We propose here a novel
      approach, based on the notion of conflicting signals and on a phenotypic
      description of cancer cells. "Phenotype" is an inherently complex notion that we
      describe in the conceptual framework of the epigenetic landscape, with a view to
      bridging the gap between theory and practice at the patient's bedside. By passing
      from theory to the description of several examples, we will illustrate how this
      approach can facilitate data analysis and the design of new strategies for cancer
      treatment. Cancer Res; 76(23); 6768-73. (c)2016 AACR.

PMID- 27872098
TI  - Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in
      Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) remains an aggressive disease without
      effective targeted therapies. In this study, we addressed this challenge by
      testing 128 FDA-approved or investigational drugs as either single agents or in
      768 pairwise drug combinations in TNBC cell lines to identify synergistic
      combinations tractable to clinical translation. Medium-throughput results were
      scrutinized and extensively analyzed for sensitivity patterns, synergy,
      anticancer activity, and were validated in low-throughput experiments. Principal
      component analysis revealed that a fraction of all upregulated or downregulated
      genes of a particular targeted pathway could partly explain cell sensitivity
      toward agents targeting that pathway. Combination therapies deemed immediately
      tractable to translation included ABT-263/crizotinib, ABT-263/paclitaxel,
      paclitaxel/JQ1, ABT-263/XL-184, and paclitaxel/nutlin-3, all of which exhibited
      synergistic antiproliferative and apoptotic activity in multiple TNBC
      backgrounds. Mechanistic investigations of the ABT-263/crizotinib combination
      offering a potentially rapid path to clinic demonstrated RTK blockade, inhibition
      of mitogenic signaling, and proapoptotic signal induction in basal and
      mesenchymal stem-like TNBC. Our findings provide preclinical proof of concept for
      several combination treatments of TNBC, which offer near-term prospects for
      clinical translation. Cancer Res; 77(2); 566-78. (c)2016 AACR.

PMID- 27872100
TI  - Regeneration of CD8alphabeta T Cells from T-cell-Derived iPSC Imparts Potent
      Tumor Antigen-Specific Cytotoxicity.
AB  - Although adoptive transfer of cytotoxic T lymphocytes (CTL) offer a promising
      cancer therapeutic direction, the generation of antigen-specific CTL from
      patients has faced difficulty in efficient expansion in ex vivo culture. To
      resolve this issue, several groups have proposed that induced pluripotent stem
      cell technology be applied for the expansion of antigen-specific CTL, which
      retain expression of the same T-cell receptor as original CTL. However, in these
      previous studies, the regenerated CTL are mostly of the CD8alphaalpha+ innate
      type and have less antigen-specific cytotoxic activity than primary CTL. Here we
      report that, by stimulating purified iPSC-derived CD4/CD8 double-positive cells
      with anti-CD3 antibody, T cells expressing CD8alphabeta were generated and
      exhibited improved antigen-specific cytotoxicity compared with CD8alphaalpha+
      CTL. Failure of CD8alphabeta T-cell production using the previous method was
      found to be due to killing of double-positive cells by the double-negative cells
      in the mixed cultures. We found that WT1 tumor antigen-specific CTL regenerated
      by this method prolonged the survival of mice bearing WT1-expressing leukemic
      cells. Implementation of our methods may offer a useful clinical tool. Cancer
      Res; 76(23); 6839-50. (c)2016 AACR.

PMID- 27872097
TI  - Menin and Daxx Interact to Suppress Neuroendocrine Tumors through Epigenetic
      Control of the Membrane Metallo-Endopeptidase.
AB  - Neuroendocrine tumors (NET) often harbor loss-of-function mutations in the MEN1
      and DAXX tumor suppressor genes. Here, we report that the products of these
      genes, menin and Daxx, interact directly with each other to suppress the
      proliferation of NET cells, to a large degree by inhibiting expression of the
      membrane metallo-endopeptidase (MME). Menin and Daxx were required to enhance
      histone H3 lysine9 trimethylation (H3K9me3) at the MME promoter, as mediated
      partly by the histone H3 methyltransferase SUV39H1. Notably, the menin T429K
      mutation associated with a NET syndrome reduced Daxx binding, MME repression, and
      proliferation of NET cells. Conversely, inhibition of MME in NET cells repressed
      proliferation and tumor growth in vivo Our findings reveal a previously
      unappreciated cross-talk between two crucial tumor suppressor genes thought to
      work by independent pathways, focusing on MME as a common target of menin/Daxx to
      treat NET. Cancer Res; 77(2); 401-11. (c)2016 AACR.

PMID- 27872101
TI  - Natural Killer Cells to the Attack: Combination Therapy against Neuroblastoma.
AB  - TGFbeta in the tumor microenvironment diminishes natural killer (NK) cell
      mediated anti-disialoganglioside (anti-GD2) mAb elimination of neuroblastoma
      cells. Consequently, blockade of TGFbeta signaling with galunisertib in
      combination with the anti-GD2 mAb dinutuximab plus adoptively transferred NK
      cells is a promising tool for the treatment of neuroblastoma. Clin Cancer Res;
      23(3); 615-7. (c)2016 AACRSee related article by Tran et al., p. 804.

PMID- 27872104
TI  - Potential role for BCG in treatment of autoimmune diseases.

PMID- 27872102
TI  - E6 and E7 Antibody Levels Are Potential Biomarkers of Recurrence in Patients with
      Advanced-Stage Human Papillomavirus-Positive Oropharyngeal Squamous Cell
      Carcinoma.
AB  - Purpose: There is a paucity of biomarkers to predict failure in human
      papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC)
      following curative therapy. E6/E7 viral oncoproteins are constitutively expressed
      in HPV+ tumors and highly immunogenic, resulting in readily detected serum
      antibodies. The purpose of this study is to determine whether serum E6 and E7
      antibody levels can potentially serve as a biomarker of recurrence in patients
      with HPV+OPSCC.Experimental Design: We evaluated E6/E7 antibody levels in
      patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC
      receiving definitive chemoradiation under a uniform protocol from 2003 to 2010.
      Baseline and longitudinal serum samples were obtained from our archived
      repository. E6/E7 serum levels were measured using a glutathione-S-transferase
      capture ELISA and quantified by approximating the area under the dilution curve,
      and were analyzed using ANOVA and linear mixed model for longitudinal
      analysis.Results: We compared 22 HPV+OPSCC patients who developed recurrence with
      30 patients who remained disease-free. There were no differences in T
      classification, N classification, disease subsite, or smoking status between the
      groups. In a longitudinal analysis, recurrent patients had significantly higher
      E6 and E7 serum antibody levels than the nonrecurrent patients over the follow-up
      period (P = 0.02 and P = 0.002, respectively). Patients who recurred had a lower
      clearance of E7 antibody than patients who remained disease-free (P =
      0.0016).Conclusions: Patients with HPV+OPSCC whose disease recurs have a lower
      clearance of E6 and E7 antibodies than patients who do not have recurrence. The
      ratio of E7 antibody at disease recurrence compared with baseline is potentially
      a clinically significant measurement of disease status in HPV+OPSCC. Clin Cancer
      Res; 23(11); 2723-9. (c)2016 AACR.

PMID- 27872103
TI  - Rapid and Continued T-Cell Differentiation into Long-term Effector and Memory
      Stem Cells in Vaccinated Melanoma Patients.
AB  - Purpose: Patients with cancer benefit increasingly from T-cell-based therapies,
      such as adoptive T-cell transfer, checkpoint blockade, or vaccination. We have
      previously shown that serial vaccinations with Melan-AMART-126-35 peptide, CpG-B,
      and incomplete Freund adjuvant (IFA) generated robust tumor-specific CD8 T-cell
      responses in patients with melanoma. Here, we describe the detailed kinetics of
      early- and long-term establishment of T-cell frequency, differentiation (into
      memory and effector cells), polyfunctionality, and clonotype repertoire induced
      by vaccination.Experimental Design: Twenty-nine patients with melanoma were
      treated with multiple monthly subcutaneous vaccinations consisting of CpG-B, and
      either the native/EAA (n = 13) or the analogue/ELA (n = 16) Melan-AMART-126-35
      peptide emulsified in IFA. Phenotypes and functionality of circulating Melan-A
      specific CD8 T cells were assessed directly ex vivo by multiparameter flow
      cytometry, and TCR clonotypes were determined ex vivo by mRNA transcript analyses
      of individually sorted cells.Results: Our results highlight the determining
      impact of the initial vaccine injections on the rapid and strong induction of
      differentiated effector T cells in both patient cohorts. Moreover, long-term
      polyfunctional effector T-cell responses were associated with expansion of stem
      cell-like memory T cells over time along vaccination. Dominant TCR clonotypes
      emerged early and persisted throughout the entire period of observation.
      Interestingly, one highly dominant clonotype was found shared between memory and
      effector subsets.Conclusions: Peptide/CpG-B/IFA vaccination induced powerful long
      term T-cell responses with robust effector cells and stem cell-like memory cells.
      These results support the further development of CpG-B-based cancer vaccines,
      either alone or as specific component of combination therapies. Clin Cancer Res;
      23(13); 3285-96. (c)2016 AACR.

PMID- 27872108
TI  - Nitrofurantoin, an Excellent Empiric Choice for Outpatient Cystitis.

PMID- 27872106
TI  - Methylenetetrahydrofolate Dehydrogenase 1 Polymorphisms Modify the Associations
      of Plasma Glycine and Serine With Risk of Acute Myocardial Infarction in Patients
      With Stable Angina Pectoris in WENBIT (Western Norway B Vitamin Intervention
      Trial).
AB  - BACKGROUND: Serine and glycine interconversion and methylenetetrahydrofolate
      dehydrogenase 1 (MTHFD1)-mediated 1-carbon transfer are the major sources of
      methyl groups for 1-carbon metabolism. Recently, plasma glycine and a common
      polymorphism in MTHFD1 have been associated with risk of acute myocardial
      infarction (AMI). It is, therefore, of interest to explore if these 2 pathways
      interact in relation to AMI. METHODS AND RESULTS: A total of 2571 participants in
      the WENBIT (Western Norway B Vitamin Intervention Trial) undergoing coronary
      angiography for stable angina pectoris were studied. Associations of plasma
      serine and glycine concentrations with risk of AMI across 2 common and functional
      MTHFD1 polymorphisms (rs2236225 and rs1076991) were explored in Cox regression
      models. During a median follow-up of 4.7 years, 212 patients (8.2%) experienced
      an AMI. In age- and sex-adjusted analyses, plasma glycine (P<0.01), but not
      serine (P=0.52), showed an overall association with AMI. However, interactions of
      MTHFD1 rs2236225 polymorphism with both plasma serine and glycine were observed
      (Pinteraction=0.03 for both). Low plasma serine and glycine were associated with
      an increased risk of AMI among patients carrying the rs2236225 minor A allele.
      Similarly, low plasma glycine showed stronger risk relationship with AMI in the
      rs1076991 CC genotype carriers but weaker associations in patients carrying the
      minor T allele (Pinteraction=0.02). CONCLUSIONS: Our results showed that 2 common
      and functional polymorphisms in the MTHFD1 gene modulate the risk associations of
      plasma serine and glycine with AMI. These findings emphasize the possible role of
      the MTHFD1 in regulating serine and glycine metabolism in relation to
      atherosclerotic complications. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique Identifier: NCT00354081.

PMID- 27872109
TI  - Reply to "Nitrofurantoin, an Excellent Empiric Choice for Outpatient Cystitis".

PMID- 27872110
TI  - Correction for Leangapichart et al., Acquisition of mcr-1 Plasmid-Mediated
      Colistin Resistance in Escherichia coli and Klebsiella pneumoniae during Hajj
      2013 and 2014.

PMID- 27872105
TI  - Multiethnic Exome-Wide Association Study of Subclinical Atherosclerosis.
AB  - BACKGROUND: The burden of subclinical atherosclerosis in asymptomatic individuals
      is heritable and associated with elevated risk of developing clinical coronary
      heart disease. We sought to identify genetic variants in protein-coding regions
      associated with subclinical atherosclerosis and the risk of subsequent coronary
      heart disease. METHODS AND RESULTS: We studied a total of 25 109 European
      ancestry and African ancestry participants with coronary artery calcification
      (CAC) measured by cardiac computed tomography and 52 869 participants with common
      carotid intima-media thickness measured by ultrasonography within the CHARGE
      Consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology).
      Participants were genotyped for 247 870 DNA sequence variants (231 539 in exons)
      across the genome. A meta-analysis of exome-wide association studies was
      performed across cohorts for CAC and carotid intima-media thickness. APOB
      p.Arg3527Gln was associated with 4-fold excess CAC (P=3*10-10). The APOE epsilon2
      allele (p.Arg176Cys) was associated with both 22.3% reduced CAC (P=1*10-12) and
      1.4% reduced carotid intima-media thickness (P=4*10-14) in carriers compared with
      noncarriers. In secondary analyses conditioning on low-density lipoprotein
      cholesterol concentration, the epsilon2 protective association with CAC, although
      attenuated, remained strongly significant. Additionally, the presence of epsilon2
      was associated with reduced risk for coronary heart disease (odds ratio 0.77;
      P=1*10-11). CONCLUSIONS: Exome-wide association meta-analysis demonstrates that
      protein-coding variants in APOB and APOE associate with subclinical
      atherosclerosis. APOE epsilon2 represents the first significant association for
      multiple subclinical atherosclerosis traits across multiple ethnicities, as well
      as clinical coronary heart disease.

PMID- 27872111
TI  - Ultrasound imaging to tailor the treatment of acute shoulder pain: a randomised
      controlled trial in general practice.
AB  - OBJECTIVE: To determine the clinical effectiveness of ultrasound tailored
      treatment in patients with acute subacromial disorders. DESIGN: Pragmatic
      randomised controlled trial. SETTING: Dutch general practice. PARTICIPANTS:
      Patients aged 18-65 years with acute (duration <3 months) unilateral shoulder
      pain and no previous treatment, in whom the general practitioner suspected a
      subacromial disorder was enrolled. INTERVENTIONS: All patients underwent
      ultrasound imaging of the affected shoulder. Patients who were still symptomatic
      after a qualification period of 2 weeks with standard treatment were randomised
      to treatment tailored to ultrasound diagnosis (disclosure of the ultrasound
      diagnosis) or usual care (non-disclosure of the ultrasound diagnosis). PRIMARY
      OUTCOME MEASURE: Patient-perceived recovery using the Global Perceived Effect
      questionnaire at 1 year. RESULTS: 129 patients were included. 18 patients
      recovered during the 2-week qualification period, resulting in 111 randomised
      patients; 56 were allocated to ultrasound tailored treatment and 55 to usual
      care. After 1 year, no statistically significant differences in recovery were
      found between the ultrasound tailored treatment group (72.5% (37/51)) and the
      usual care group (60% (30/50), OR 2.24 (95% CI 0.72 to 6.89; p=0.16)). Also,
      healthcare use was similar. CONCLUSIONS: This study has shown no clinically
      significant difference in the primary outcome measure between the ultrasound
      tailored treatment and usual care groups. Furthermore, there was no overall
      difference in healthcare resources used between groups. Although no formal cost
      data are included, one can only assume that the ultrasound examinations are
      additional costs for the intervention group, which cannot be justified in routine
      practice based on this trial. Based on this study, no change in current pragmatic
      guidelines to incorporate early ultrasound imaging can be recommended. TRIAL
      REGISTRATION NUMBER: NTR2403; Results.

PMID- 27872112
TI  - Too much detention? Street Triage and detentions under Section 136 Mental Health
      Act in the North-East of England: a descriptive study of the effects of a Street
      Triage intervention.
AB  - OBJECTIVES: To describe the impact of Street Triage (ST) on the number and rate
      of Section 136 Mental Health Act (S136) detentions in one NHS Mental Health and
      Disability Trust (Northumberland, Tyne and Wear (NTW)). DESIGN: Comparative
      descriptive study of numbers and rates of S136 detentions prior to and following
      the introduction of ST in NTW. More detailed data were obtained from one local
      authority in the NTW area. SETTING: NTW, a secondary care NHS Foundation Trust
      providing mental health and disability services in the north-east of England, in
      conjunction with Northumbria Police Service. PARTICIPANTS: People being detained
      under S136 Mental Health Act (MHA). Routine data on S136 detentions and ST
      interventions were obtained from NTW, Northumbria Police, Sunderland Hospitals
      NHS Foundation Trust and Sunderland Local Authority. INTERVENTIONS: Introduction
      of a ST service in NTW. The main outcome measures were routinely collected data
      on the number and rate of ST interventions as well as patterns of the numbers and
      rates of S136 detentions. These were collected retrospectively. RESULTS: The
      annual rate of S136 detentions reduced by 56% in the first year of ST (from 59.8
      per 100 000 population to 26.4 per 100 000). There was a linear relationship
      between the rate of ST in each locality and the reduction in rate of S136
      detentions. There were 1623 ST contacts in the first 3 localities to have a ST
      service during its first year; there were also 403 fewer S136 detentions. Data
      from Sunderland indicate a 78% reduction in S136 use and a significant reduction
      in the number and proportion of adult admissions that originated from S136
      detentions. CONCLUSIONS: There is evidence to support the hypothesis that ST
      decreases the rate of s136 detention. When operating across the whole of NTW, ST
      resulted in 50 fewer S136 detentions a month, which represents a substantial
      reduction.

PMID- 27872113
TI  - Does integrated care reduce hospital activity for patients with chronic diseases?
      An umbrella review of systematic reviews.
AB  - OBJECTIVE: To summarise the evidence regarding the effectiveness of integrated
      care interventions in reducing hospital activity. DESIGN: Umbrella review of
      systematic reviews and meta-analyses. SETTING: Interventions must have delivered
      care crossing the boundary between at least two health and/or social care
      settings. PARTICIPANTS: Adult patients with one or more chronic diseases. DATA
      SOURCES: MEDLINE, Embase, ASSIA, PsycINFO, HMIC, CINAHL, Cochrane Library (HTA
      database, DARE, Cochrane Database of Systematic Reviews), EPPI-Centre, TRIP,
      HEED, manual screening of references. OUTCOME MEASURES: Any measure of hospital
      admission or readmission, length of stay (LoS), accident and emergency use,
      healthcare costs. RESULTS: 50 reviews were included. Interventions focused on
      case management (n=8), chronic care model (CCM) (n=9), discharge management
      (n=15), complex interventions (n=3), multidisciplinary teams (MDT) (n=10) and
      self-management (n=5). 29 reviews reported statistically significant improvements
      in at least one outcome. 11/21 reviews reported significantly reduced emergency
      admissions (15-50%); 11/24 showed significant reductions in all-cause (10-30%) or
      condition-specific (15-50%) readmissions; 9/16 reported LoS reductions of 1-7
      days and 4/9 showed significantly lower A&E use (30-40%). 10/25 reviews reported
      significant cost reductions but provided little robust evidence. Effective
      interventions included discharge management with postdischarge support, MDT care
      with teams that include condition-specific expertise, specialist nurses and/or
      pharmacists and self-management as an adjunct to broader interventions.
      Interventions were most effective when targeting single conditions such as heart
      failure, and when care was provided in patients' homes. CONCLUSIONS: Although all
      outcomes showed some significant reductions, and a number of potentially
      effective interventions were found, interventions rarely demonstrated
      unequivocally positive effects. Despite the centrality of integrated care to
      current policy, questions remain about whether the magnitude of potentially
      achievable gains is enough to satisfy national targets for reductions in hospital
      activity. TRIAL REGISTRATION NUMBER: CRD42015016458.

PMID- 27872114
TI  - Relationship between women's smoking and laryngeal disorders based on the urine
      cotinine test: results of a national population-based survey.
AB  - OBJECTIVES: There is a possibility of underestimation in the smoking rate
      surveyed by self-reported questionnaires. This study investigated the difference
      between the Korean female smoking rate as determined by self-reports and that
      determined by a biochemical test and elucidated the relationship between women's
      smoking and laryngeal disorders. DESIGN: Nationwide cross-sectional survey.
      SETTING: 2008 Korea National Health and Nutrition Examination Survey.
      PARTICIPANTS: 1849 women who completed the health survey, urinary cotinine test
      and laryngoscope examinations. MAIN OUTCOME MEASURE: This study defined smokers
      as those with urine cotinine contents of 50 ng/mL and over. Confounding factors
      included age, level of education, household income, occupation and problem
      drinking in the past year. For statistical tests, OR and 95% CI were presented by
      using complex samples logistic regression. RESULTS: While there was no
      relationship between smoking as determined by a self-reported questionnaire and
      laryngeal disorders, smoking as determined by the urine cotinine test had a
      significant relationship with laryngeal disorders (p<0.05). After all the
      confounding factors were adjusted, those with urine cotinine concentrations of
      over 50 ng/mL had a 2.1 times higher risk of laryngeal disorders than those with
      urine cotinine concentrations of <50 ng/mL (OR=2.05, 95% CI 1.11 to 3.78)
      (p<0.05). CONCLUSIONS: This national cross-sectional study verified that smoking
      is a significant risk factor for laryngeal disorders. Longitudinal studies are
      required to identify the causal relationship between smoking and laryngeal
      disorders.

PMID- 27872115
TI  - Early Diagnosis of Gestational Diabetes Mellitus (EDoGDM) study: a protocol for a
      prospective, longitudinal cohort study.
AB  - INTRODUCTION: A diagnosis of gestational diabetes mellitus (GDM) in low-risk
      pregnant women is based on an oral glucose tolerance test (OGTT) between 24 and
      28 gestational weeks. However, there is insufficient evidence for why the test is
      performed in this time period. Moreover, the fetus may be exposed to
      hyperglycaemia prior to the current testing time frame, making earlier
      administration potentially advantageous. The main purpose of the present study is
      to investigate the GDM diagnostic value of an OGTT performed at 18-20 gestational
      weeks. The results of the study may provide scientific insight into the most
      beneficial time of OGTT for pregnant women. METHODS AND ANALYSIS: As a
      prospective, longitudinal cohort study, the Early Diagnosis of Gestational
      Diabetes Mellitus (EDoGDM) study will recruit 570 pregnant women who meet the
      inclusion and exclusion criteria outlined below. OGTTs will be performed between
      18 and 20 gestational weeks (early OGTT) and 24-28 gestational weeks (regular
      OGTT). Clinical and laboratory information of the mother and their offspring will
      be collected for analysis. The prevalence of GDM at 18-20 gestational weeks will
      be described, and the sensitivity, specificity, positive predictive value and
      negative predictive value of early OGTT on diagnosis of GDM will be studied.
      Clinical outcomes associated with hyperglycaemia will be compared between groups
      diagnosed by early or regular OGTT. ETHICS AND DISSEMINATION: The study was
      approved by The Ethical Committees of The First Affiliated Hospital of Sun Yat
      sen University (number 2016-042). Signed informed consent will be obtained from
      all participants. The results of this study will be disseminated in peer-reviewed
      journals. TRIAL REGISTRATION NUMBER: NCT02740283.

PMID- 27872116
TI  - Reporting quality of abstracts of trials published in top five pain journals: a
      protocol for a systematic survey.
AB  - INTRODUCTION: Abstracts of randomised controlled trials (RCTs) are often the
      first and the only source read in a journal by busy healthcare providers. This
      necessitates good reporting of abstracts. The quality of reporting of abstracts,
      though gradually improving over time, is still not uniform across medical
      journals. Improvement in completeness of reporting of abstracts has been
      documented in general medical journals after the publication of the consolidated
      standards of reporting trials (CONSORT) extension for abstracts in 2008.
      Currently, this aspect has not been assessed with regards to pain journals. This
      study aims to compare the completeness of reporting of abstracts before and after
      the publication of CONSORT statement for abstracts in five pain journals. METHODS
      AND ANALYSES: The abstracts of RCTs published from 1 January 2005 to 31 December
      2007 (pre-CONSORT) and from 1 January 2013 to 31 December 2015 (post-CONSORT)
      will be assessed for the quality of reporting. Studies without abstracts, non
      English abstracts, abstracts not reporting on RCTs or on humans and conference
      abstracts will be excluded. A thorough search of MEDLINE will be carried out in
      April 2016. All identified studies will be screened for inclusion based on titles
      and abstracts. Data will be extracted by two sets of independent reviewers for
      each abstract in duplicate regarding compliance with CONSORT statement for
      abstracts. Full-text review will be performed to obtain additional
      characteristics which are likely to affect reporting quality. The unadjusted and
      adjusted differences in the mean number of items reported will be analysed using
      a two sample t-test and generalised estimation equation in SPSS. ETHICS AND
      DISSEMINATION: As far as we know, this is the first study to evaluate reporting
      quality of abstracts of pain journals based on CONSORT extension for abstracts.
      The findings of this study will be disseminated by a presentation at a conference
      and through publication in a peer-reviewed journal. Ethics committee approval was
      not sought for this survey.

PMID- 27872117
TI  - Protocol for a multicentre randomised feasibility trial evaluating early Surgery
      Alone In LOw Rectal cancer (SAILOR).
AB  - INTRODUCTION: There are 11 500 rectal cancers diagnosed annually in the UK.
      Although surgery remains the primary treatment, there is evidence that
      preoperative radiotherapy (RT) improves local recurrence rates. High-quality
      surgery in rectal cancer is equally important in minimising local recurrence.
      Advances in MRI-guided prediction of resection margin status and improvements in
      abdominoperineal excision of the rectum (APER) technique supports a reassessment
      of the contribution of preoperative RT. A more selective approach to RT may be
      appropriate given the associated toxicity. METHODS AND ANALYSIS: This trial will
      explore the feasibility of a definitive trial evaluating the omission of RT in
      resectable low rectal cancer requiring APER. It will test the feasibility of
      randomising patients to (1) standard care (neoadjuvant long course RT+/
      chemotherapy and APER, or (2) APER surgery alone for cT2/T3ab N0/1 low rectal
      cancer with clear predicted resection margins on MRI. RT schedule will be 45 Gy
      over 5 weeks as current standard, with restaging and surgery after 8-12 weeks.
      Recruitment will be for 24 months with a minimum 12-month follow-up. OBJECTIVES:
      Objectives include testing the ability to recruit, consent and retain patients,
      to quantify the number of patients eligible for a definitive trial and to test
      feasibility of outcomes measures. These include locoregional recurrence rates,
      distance to circumferential resection margin, toxicity and surgical complications
      including perineal wound healing, quality of life and economic analysis. The
      quality of MRI staging, RT delivery and surgical specimen quality will be closely
      monitored. ETHICS AND DISSEMINATION: The trial is approved by the Regional Ethics
      Committee and Health Research Authority (HRA) or equivalent. Written informed
      consent will be obtained. Serious adverse events will be reported to Swansea
      Trials Unit (STU), the ethics committee and trial sites. Trial results will be
      submitted for peer review publication and to trial participants. TRIAL
      REGISTRATION NUMBER: ISRCTN02406823.

PMID- 27872118
TI  - Cost burden of type 2 diabetes in Germany: results from the population-based KORA
      studies.
AB  - OBJECTIVE: To examine the impact of type 2 diabetes on direct and indirect costs
      and to describe the effect of relevant diabetes-related factors, such as type of
      treatment or glycaemic control on direct costs. DESIGN: Bottom-up excess cost
      analysis from a societal perspective based on population-based survey data.
      PARTICIPANTS: 9160 observations from 6803 individuals aged 31-96 years (9.6% with
      type 2 diabetes) from the population-based KORA (Cooperative Health Research in
      the Region of Augsburg) studies in Southern Germany. OUTCOME MEASURES: Healthcare
      usage, productivity losses, and resulting direct and indirect costs. METHODS:
      Information on diabetes status, biomedical/sociodemographic variables, medical
      history and on healthcare usage and productivity losses was assessed in
      standardised interviews and examinations. Healthcare usage and productivity
      losses were costed with reference to unit prices and excess costs of type 2
      diabetes were calculated using generalised linear models. RESULTS: Individuals
      with type 2 diabetes had 1.81 (95% CI 1.56 to 2.11) times higher direct (?3352 vs
      ?1849) and 2.07 (1.51 to 2.84) times higher indirect (?4103 vs ?1981) annual
      costs than those without diabetes. Cardiovascular complications, a long diabetes
      duration and treatment with insulin were significantly associated with increased
      direct costs; however, glycaemic control was only weakly insignificantly
      associated with costs. CONCLUSIONS: This study illustrates the substantial direct
      and indirect societal cost burden of type 2 diabetes in Germany. Strong effort is
      needed to optimise care to avoid progression of the disease and costly
      complications.

PMID- 27872119
TI  - Efficacy of intravenous nicorandil for fractional flow reserve assessment: study
      protocol for a crossover randomised trial.
AB  - INTRODUCTION: Nicorandil has vasodilatory effects on both the epicardial coronary
      arteries and the coronary microvasculature, thereby increasing coronary blood
      flow. Intravenous administration of nicorandil can be applicable for fractional
      flow reserve (FFR) measurement as a hyperaemic agent and a possible alternative
      to adenosine. However, the effectiveness of intravenous nicorandil infusion for
      FFR measurement is largely unclear. METHODS AND ANALYSIS: This crossover
      randomised study is being performed to investigate the efficacy of intravenous
      administration of nicorandil for FFR measurement. Patients with an intermediate
      coronary artery stenosis who satisfy the eligibility criteria undergo FFR
      measurement with a consecutive randomised order of patient-blind infusions of
      continuous intravenous administration of adenosine and a single bolus intravenous
      administration of nicorandil. The primary end point of the study is the agreement
      between the FFR values obtained by the intravenous nicorandil and those obtained
      by the intravenous adenosine. Recruitment of this trial started in November 2015
      and will end in March 2017, or until a total of 50 participants have been
      recruited. ETHICS AND DISSEMINATION: The protocol was approved by the
      Institutional Review Board at Chiba University Hospital. Study findings will be
      published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000019309;
      Pre-results.

PMID- 27872121
TI  - Qualitative study of physicians' varied uses of biomedical research in the USA.
AB  - OBJECTIVE: To investigate the nature of physicians' use of research evidence in
      experimental conditions of open access to inform training and policy. DESIGN:
      This qualitative study was a component of a larger mixed-methods initiative that
      provided 336 physicians with relatively complete access to research literature
      via PubMed and UpToDate, for 1 year via an online portal, with their usage
      recorded in web logs. Using a semistructured interview protocol, a subset of 38
      physician participants were interviewed about their use of research articles in
      general and were probed about their reasons for accessing specific articles as
      identified through their web logs. Transcripts were analysed using a general
      inductive approach. SETTING: Physician participants were recruited from and
      registered in the USA. PARTICIPANTS: 38 physicians from 16 US states, engaged in
      22 medical specialties, possessing more than 1 year of experience postresidency
      training participated. RESULTS: 26 participants attested to the value of
      consulting research literature within the context of the study by making
      reference to their roles as clinicians, educators, researchers, learners,
      administrators and advocates. The physicians reported previously encountering
      what they experienced as a prohibitive paywall barrier to the research literature
      and other frustrations with the nature of information systems, such as the need
      for passwords. CONCLUSIONS: The findings, against the backdrop of growing open
      access to biomedical research, indicate that a minority of physicians, at least
      initially, is likely to seek out and use research and do so in a variety of
      common roles. Physicians' use of research in these roles has not traditionally
      been part of their training or part of the considerations for open access
      policies. The findings have implications for educational and policy initiatives
      directed towards increasing the effectiveness of this access to and use of
      research in improving the quality of healthcare.

PMID- 27872120
TI  - Large-scale implementation of disease control programmes: a cost-effectiveness
      analysis of long-lasting insecticide-treated bed net distribution channels in a
      malaria-endemic area of western Kenya-a study protocol.
AB  - INTRODUCTION: Historically, Kenya has used various distribution models for long
      lasting insecticide-treated bed nets (LLINs) with variable results in population
      coverage. The models presently vary widely in scale, target population and
      strategy. There is limited information to determine the best combination of
      distribution models, which will lead to sustained high coverage and are
      operationally efficient and cost-effective. Standardised cost information is
      needed in combination with programme effectiveness estimates to judge the
      efficiency of LLIN distribution models and options for improvement in
      implementing malaria control programmes. The study aims to address the
      information gap, estimating distribution cost and the effectiveness of different
      LLIN distribution models, and comparing them in an economic evaluation. METHODS
      AND ANALYSIS: Evaluation of cost and coverage will be determined for 5 different
      distribution models in Busia County, an area of perennial malaria transmission in
      western Kenya. Cost data will be collected retrospectively from health
      facilities, the Ministry of Health, donors and distributors. Programme
      effectiveness data, defined as the number of people with access to an LLIN per
      1000 population, will be collected through triangulation of data from a
      nationally representative, cross-sectional malaria survey, a cross-sectional
      survey administered to a subsample of beneficiaries in Busia County and LLIN
      distributors' records. Descriptive statistics and regression analysis will be
      used for the evaluation. A cost-effectiveness analysis will be performed from a
      health-systems perspective, and cost-effectiveness ratios will be calculated
      using bootstrapping techniques. ETHICS AND DISSEMINATION: The study has been
      evaluated and approved by Kenya Medical Research Institute, Scientific and
      Ethical Review Unit (SERU number 2997). All participants will provide written
      informed consent. The findings of this economic evaluation will be disseminated
      through peer-reviewed publications.

PMID- 27872123
TI  - Effect of External Ankle Support on Ankle and Knee Biomechanics During the
      Cutting Maneuver in Basketball Players.
AB  - BACKGROUND: Despite the high prevalence of lower extremity injuries in female
      basketball players as well as a high proportion of athletes who wear ankle
      braces, there is a paucity of research pertaining to the effects of ankle bracing
      on ankle and knee biomechanics during basketball-specific tasks. PURPOSE: To
      compare the effects of a lace-up brace (ASO), a hinged brace (Active T2), and no
      ankle bracing (control) on ankle and knee joint kinematics and joint reaction
      forces in female basketball athletes during a cutting maneuver. STUDY DESIGN:
      Controlled laboratory study. METHODS: Twenty healthy, semi-elite female
      basketball players performed a cutting task under both ankle brace conditions
      (lace-up ankle brace and hinged ankle brace) and a no-brace condition. The 3
      dimensional kinematics of the ankle and knee during the cutting maneuver were
      measured with an 18-camera motion analysis system (250 Hz), and ground-reaction
      force data were collected by use of a multichannel force plate (2000 Hz) to
      quantify ankle and knee joint reaction forces. Conditions were randomized using a
      block randomization method. RESULTS: Compared with the control condition, the
      hinged ankle brace significantly restricted peak ankle inversion (mean
      difference, 1.7 degrees ; P = .023). No significant difference was found between
      the lace-up brace and the control condition ( P = .865). Compared with the lace
      up brace, the hinged brace significantly reduced ankle and knee joint compressive
      forces at the time of peak ankle dorsiflexion (mean difference, 1.5 N/kg [ P =
      .018] and 1.4 N/kg [ P = .013], respectively). Additionally, the hinged ankle
      brace significantly reduced knee anterior shear forces compared with the lace-up
      brace both during the deceleration phase and at peak ankle dorsiflexion (mean
      difference, 0.8 N/kg [ P = .018] and 0.9 N/kg [ P = .011], respectively).
      CONCLUSION: The hinged ankle brace significantly reduced ankle inversion compared
      with the no-brace condition and reduced ankle and knee joint forces compared with
      the lace-up brace in a female basketball population during a cutting task.
      Compared with the lace-up brace, the hinged brace may be a better choice of
      prophylactic ankle support for female basketball players from a biomechanical
      perspective. However, both braces increased knee internal rotation and knee
      abduction angles, which may be problematic for a population that already has a
      high prevalence of knee injuries.

PMID- 27872122
TI  - Polymyxin B-immobilised haemoperfusion and mortality in critically ill patients
      with sepsis/septic shock: a protocol for a systematic review and meta-analysis.
AB  - INTRODUCTION: Polymyxin-B immobilised haemoperfusion (PMX-HP) is a promising
      adjuvant strategy for the treatment of sepsis and septic shock. PMX-HP therapy
      works by clearing circulating endotoxin through binding to polymyxin-immobilised
      fibres during haemoperfusion. Small clinical trials have shown that PMX-HP
      therapy is associated with improved haemodynamic profile, oxygenation and
      survival. However, clear inferences have been largely inconclusive due to
      limitations in study design (eg, small, unblinded) and generalisability. We
      therefore propose to perform an up-to-date systematic review and evidence
      synthesis to describe the efficacy, safety and effectiveness of PMX-HP for adult
      patients with sepsis or septic shock. METHODS AND ANALYSIS: We will search the
      following databases from 1946 to 2016 MEDLINE (Ovid), EMBASE (Ovid), Cochrane
      Library, Health Technology Assessment Database (HTA), Cumulative Index to Nursing
      and Allied Health Literature (CINAHL), PubMed and 'Igaku Chuo Zasshi' (ICHUSHI)
      for randomised controlled trials of PMX-HP in critically ill patients with sepsis
      or septic shock. There will be no language restrictions in the electronic search
      for studies. Two reviewers will extract data and appraise the quality of each
      study independently. The primary outcome will be the pooled risk ratio of 28-day
      all-cause mortality. Serious adverse events and changes in organ dysfunction
      scores will also be evaluated. The secondary outcomes will be 90-day all-cause
      mortality, changes in haemodynamic profile and endotoxin levels, and health
      services use. ETHICS AND DISSEMINATION: Our systematic review will synthesise the
      evidence on use of the PMX-HP as an adjuvant therapy in sepsis/septic shock to
      improve patient-centred, physiological and health services outcomes. Research
      ethics is not required for this review. The study will be disseminated by peer
      reviewed publication and conference presentation. TRIAL REGISTRATION NUMBER:
      CRD42016038356.

PMID- 27872124
TI  - Incidence, Mechanisms, and Severity of Match-Related Collegiate Men's Soccer
      Injuries on FieldTurf and Natural Grass Surfaces: A 6-Year Prospective Study.
AB  - BACKGROUND: Numerous injuries have been attributed to playing on artificial turf.
      More recently, newer generations of artificial turf have been developed to
      duplicate the playing characteristics of natural grass. Although artificial turf
      has been deemed safer than natural grass in some studies, few long-term studies
      have been conducted comparing match-related collegiate soccer injuries between
      the 2 playing surfaces. HYPOTHESIS: Collegiate male soccer athletes do not
      experience any difference in the incidence, mechanisms, or severity of match
      related injuries between FieldTurf and natural grass. STUDY DESIGN: Cohort study;
      Level of evidence, 2. METHODS: Male soccer athletes from 11 universities were
      evaluated over 6 seasons. Demographic features and predictors included player
      position, cleat design, player weight, turf age, and environmental factors.
      Outcomes of interest included injury incidence, injury category, time loss,
      injury mechanism and situation, type of injury, injury grade and anatomic
      location, injury severity, head and lower extremity trauma, and elective medical
      procedures. All match-related injuries were evaluated by the attending head
      athletic trainer and team physicians on site and subsequently in the physician's
      office when further follow-up and treatment were deemed necessary. In sum, 765
      collegiate games were evaluated for match-related soccer injuries sustained on
      FieldTurf or natural grass during 6 seasons. RESULTS: Overall, 380 team games
      (49.7%) were played on FieldTurf versus 385 team games (50.3%) played on natural
      grass. A total of 722 injuries were documented, with 268 (37.1%) occurring on
      FieldTurf and 454 (62.9%) on natural grass. Multivariate analysis per 10 team
      games indicated a significant playing surface effect: F2,720 = 7.260, P = .001. A
      significantly lower total injury incidence rate (IIR) of 7.1 (95% CI, 6.6-7.5)
      versus 11.8 (95% CI, 11.3-12.2; P < .0001) and lower rate of substantial
      injuries, 0.7 (95% CI, 0.5-1.0) versus 1.9 (95% CI, 1.5-2.3; P < .03), were
      documented on FieldTurf versus natural grass, respectively. Analyses also
      indicated significantly less trauma on FieldTurf when comparing injury category,
      time loss, player position, injury mechanism and situation, injuries under
      various environmental conditions, cleat design, turf age, anatomic location, and
      elective medical procedures. No significant difference (F11,710 = 0.822, P =
      .618) between surfaces by knee injury was observed, with the majority of knee
      injuries involving patellar tendinopathies/syndromes followed by medial
      collateral ligament injuries on both surfaces. CONCLUSION: Although similarities
      existed between FieldTurf and natural grass during competitive match play,
      FieldTurf is, in many cases, safer than natural grass when comparing injuries in
      collegiate men's soccer. The findings of this study, however, may not be
      generalizable to other levels of competition or to other artificial surfaces.

PMID- 27872125
TI  - Results of Arthroscopic Bankart Repair for Anterior-Inferior Shoulder Instability
      at 13-Year Follow-up.
AB  - BACKGROUND: Anterior-inferior shoulder instability is a common injury in young
      patients, particularly those practicing overhead-throwing sports. Long-term
      results after open procedures are well studied and evaluated. However, the long
      term results after arthroscopic repair and risk factors of recurrence require
      further assessment. HYPOTHESIS: Arthroscopic Bankart repair results are
      comparable with those of open repair as described in the literature. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: A total of 180 shoulders with
      anterior-inferior shoulder instability were stabilized arthroscopically, met the
      inclusion criteria and the patients were able to be contacted at a minimum of 10
      year follow-up. Of these patients, 143 agreed to participate in the study.
      Assessment was performed clinically in 104 patients using the American Shoulder
      and Elbow Surgeons score, Constant score, American Academy of Orthopaedic
      Surgeons score, Rowe score, and the Dawson 12-item questionnaire. The Samilson
      Prieto score was used to assess degenerative arthropathy in radiographs available
      for 100 shoulders. Additionally, 15 patients participated through a specific
      questionnaire and 24 patients through a telephone survey. RESULTS: The overall
      redislocation rate was 18.18%. Redislocation rates for the different types of
      fixation devices were as follows: FASTak/Bio-FASTak, 15.1% (17/112); SureTac,
      26.3% (5/19); and Panalok, 33.3% (4/12). Concomitant superior labral anterior
      posterior repair had no effect on clinical outcome. Redislocation rate was
      significantly affected by the patient's age and duration of postoperative
      rehabilitation. Redislocation rate tended to be higher if there had been more
      than 1 dislocation preoperatively ( P = .098). Severe dislocation arthropathy was
      observed in 12% of patients, and degenerative changes were significantly
      correlated with the number of preoperative dislocations, patient age, and number
      of anchors. The patient satisfaction rate was 92.3%, and return to the preinjury
      sport level was possible in 49.5%. CONCLUSION: Clinical outcome at a mean follow
      up of 13 years after arthroscopic repair of anterior-inferior shoulder
      instability is comparable with the reported results of open Bankart repair in the
      literature and allows management of concomitant lesions arthroscopically.
      Modifiable risk factors of postoperative redislocation and arthropathy must be
      considered. Stabilization after the first-time dislocation achieves better
      clinical and radiological outcomes than after multiple dislocations.

PMID- 27872126
TI  - Multiple Ligament Reconstruction Femoral Tunnels: Intertunnel Relationships and
      Guidelines to Avoid Convergence.
AB  - BACKGROUND: Knee dislocations often require multiple concurrent ligament
      reconstructions, which involve creating several tunnels in the distal femur.
      Therefore, the risk of tunnel convergence is increased because of the limited
      bone volume within the distal aspect of the femur. PURPOSE: To assess the risk of
      tunnel convergence and determine the optimal reconstruction tunnel orientations
      for multiple ligament reconstructions in the femur. STUDY DESIGN: Descriptive
      laboratory study. METHODS: Three-dimensional knee models were developed from
      computed tomography scans of 21 patients. Medical image processing software was
      used to create tunnels for each of the primary ligamentous structures,
      replicating a surgical approach that would be used in multiple ligament
      reconstructions. Thereafter, the tunnel orientation was varied in surgically
      relevant directions to determine orientations that minimized the risk of tunnel
      convergence. The orientation of the anterior cruciate ligament (ACL) and
      posterior cruciate ligament (PCL) tunnels was held constant throughout the study,
      while the orientation of the fibular collateral ligament (FCL), popliteus tendon
      (PLT), superficial medial collateral ligament (sMCL), and posterior oblique
      ligament (POL) tunnels was varied to avoid convergence. RESULTS: A high risk of
      tunnel convergence was observed between the FCL and ACL tunnels when the FCL
      tunnel was aimed at 0 degrees  in the axial and coronal planes. Aiming the FCL
      tunnel 35 degrees  anteriorly minimized convergence with the ACL tunnel. No
      tunnel convergence was observed for the PLT tunnel aimed 35 degrees  anteriorly
      and parallel to the FCL tunnel. To avoid convergence between the sMCL and PCL
      tunnels, the sMCL tunnels should be aimed 40 degrees  proximally in the coronal
      plane and 20 degrees  to 40 degrees  anteriorly. During concomitant POL
      reconstruction, the sMCL should be aimed 40 degrees  proximally and anteriorly
      and the POL 20 degrees  proximally and anteriorly. The PLT and POL tunnels aimed
      at 0 degrees  in both the coronal and axial planes had an increased risk of
      violating the intercondylar notch. CONCLUSION: Femoral tunnel orientations during
      multiple ligament reconstructions need to be adjusted to avoid tunnel
      convergence. On the lateral side, aiming the FCL and PLT tunnels 35 degrees 
      anteriorly eliminated convergence with the ACL tunnel. On the medial side, tunnel
      convergence was avoided by orienting the sMCL tunnel 40 degrees  proximally and
      anteriorly and the POL tunnel 20 degrees  proximally and anteriorly. The POL and
      PLT tunnels aimed at 0 degrees  in the axial plane had an increased risk of
      violating the intercondylar notch. CLINICAL RELEVANCE: The risk of tunnel
      convergence with the ACL and PCL femoral tunnels can be reduced by adjusting the
      orientation of the FCL and PLT tunnels and the sMCL and POL tunnels,
      respectively.

PMID- 27872128
TI  - Correction: Molecular Heterogeneity and Receptor Coamplification Drive Resistance
      to Targeted Therapy in MET-Amplified Esophagogastric Cancer.

PMID- 27872129
TI  - Carcinogens Report Adds Seven Agents.
AB  - The National Toxicology Program has added seven new substances to its 14th Report
      on Carcinogens, bringing the total number in this congressionally mandated report
      to 248. The latest additions are the chemical trichloroethylene; cobalt metal and
      compounds that release cobalt ions in vivo; and five viruses, including HIV-1.

PMID- 27872131
TI  - Correction: Aortic valve replacement for Libman-Sacks endocarditis.

PMID- 27872127
TI  - Targeting Cancer Metabolism: Dietary and Pharmacologic Interventions.
AB  - : Most tumors display oncogene-driven reprogramming of several metabolic
      pathways, which are crucial to sustain their growth and proliferation. In recent
      years, both dietary and pharmacologic approaches that target deregulated tumor
      metabolism are beginning to be considered for clinical applications. Dietary
      interventions exploit the ability of nutrient-restricted conditions to exert
      broad biological effects, protecting normal cells, organs, and systems, while
      sensitizing a wide variety of cancer cells to cytotoxic therapies. On the other
      hand, drugs targeting enzymes or metabolites of crucial metabolic pathways can be
      highly specific and effective, but must be matched with a responsive tumor, which
      might rapidly adapt. In this review, we illustrate how dietary and pharmacologic
      therapies differ in their effect on tumor growth, proliferation, and metabolism
      and discuss the available preclinical and clinical evidence in favor of or
      against each of them. We also indicate, when appropriate, how to optimize future
      investigations on metabolic therapies on the basis of tumor- and patient-related
      characteristics. SIGNIFICANCE: To our knowledge, this is the first review article
      that comprehensively analyzes the preclinical and preliminary clinical
      experimental foundations of both dietary and pharmacologic metabolic
      interventions in cancer therapy. Among several promising therapies, we propose
      treatment personalization on the basis of tumor genetics, tumor metabolism, and
      patient systemic metabolism.Cancer Discov; 6(12); 1315-33. (c)2016 AACR.

PMID- 27872132
TI  - Cutaneous neck lesion of occult odontogenic origin: search for the tooth.
AB  - The differential diagnosis for inflammatory neck swellings is vast. A swelling of
      dental origin should be considered because, while rare, they mimic more common
      causes of neck lumps. We report the case involving a recurrent submandibular
      swelling in a young female patient that was presumed to be an epidermoid cyst by
      her general medical practitioner. After 6 months of unsuccessful treatment in the
      community, an odontogenic source was identified and treated successfully
      following referral to a local Oral and Maxillofacial department.

PMID- 27872130
TI  - A First-in-Human Phase I Study of the ATP-Competitive AKT Inhibitor Ipatasertib
      Demonstrates Robust and Safe Targeting of AKT in Patients with Solid Tumors.
AB  - : Activation of AKT signaling by PTEN loss or PIK3CA mutations occurs frequently
      in human cancers, but targeting AKT has been difficult due to the mechanism-based
      toxicities of inhibitors that target the inactive conformation of AKT.
      Ipatasertib (GDC-0068) is a novel selective ATP-competitive small-molecule
      inhibitor of AKT that preferentially targets active phosphorylated AKT (pAKT) and
      is potent in cell lines with evidence of AKT activation. In this phase I study,
      ipatasertib was well tolerated; most adverse events were gastrointestinal and
      grade 1-2 in severity. The exposures of ipatasertib >=200 mg daily in patients
      correlated with preclinical TGI90, and pharmacodynamic studies confirmed that
      multiple targets (i.e., PRAS40, GSK3beta, and mTOR) were inhibited in paired on
      treatment biopsies. Preliminary antitumor activity was observed; 16 of 52
      patients (30%), with diverse solid tumors and who progressed on prior therapies,
      had radiographic stable disease, and many of their tumors had activation of AKT.
      SIGNIFICANCE: Potent inhibition of AKT signaling with ipatasertib was associated
      with a tolerable safety profile and meaningful disease control in a subgroup of
      patients. Targeting pAKT with an ATP-competitive inhibitor provides a greater
      therapeutic window than allosteric inhibitors. Further investigation with
      ipatasertib is ongoing in phase II studies. Cancer Discov; 7(1); 102-13. (c)2016
      AACR.This article is highlighted in the In This Issue feature, p. 1.

PMID- 27872134
TI  - Metastatic trichilemmal carcinoma in a patient with breast cancer.
AB  - Trichilemmal carcinoma (TC) is described as a very rare cancer of the skin
      adnexa.1 2 Ninety per cent of the lesions present on the scalp. Prognostic
      factors in TC are limited to lymph node status and surgical margins, with no
      statistical significance observed for age or gender of the patient, size of
      tumour or locoregional recurrence. We present a 46-year-old black patient who
      developed TC during treatment for breast cancer. Postoperative histology of the
      scalp lesion excision confirmed no involved margins. At the three monthly
      appointment, the patient was reviewed and multiple, new scalp lesions were noted.
      A CT scan of the head, neck found multiple lesions on the scalp, limited to the
      soft tissue, not involving the outer table of the skull. There was bilateral
      invasion of the parotid glands. To the best of our knowledge, no syndromes or
      associations between breast cancer and adnexal skin tumours exist.

PMID- 27872133
TI  - Thyroid metastasis from lung adenocarcinoma with EML4-ALK rearrangement.
AB  - Thyroid metastases from lung cancer are very rare. A woman aged 42 years with a
      tumour in the lower lobe of the right lung was diagnosed as having lung
      adenocarcinoma positive for echinoderm microtubule-associated proteinlike 4
      anaplastic lymphoma kinase. Positron emission tomography demonstrated
      fluorodeoxyglucose accumulation in the lower lobe of the right lung, the right
      thyroid lobe and both adrenal glands. We performed fine-needle aspiration biopsy
      (FNAB) and used reverse transcriptase-PCR (RT-PCR) to diagnose the patient as
      having metastatic lung adenocarcinoma to the thyroid gland. We believe that FNAB
      combined with RT-PCR can be an effective method for diagnosing metastatic lung
      adenocarcinoma to the thyroid gland.

PMID- 27872135
TI  - Successful improvement of Buschke-Lowenstein tumour in an HIV-infected patient
      with antiretroviral therapy alone.
AB  - Buschke-Lowenstein tumour (BLT), also defined as giant condyloma acuminatum, is a
      rare exophytic tumour affecting the anogenital and perianal regions associated
      with human papillomavirus (HPV) infections, with a potential of malignant
      transformation and which is at a greater risk in T-cell mediated immunodeficient
      patients. Different therapeutic options, alone or in combination, have been
      reported for the treatment of BLT including local therapy but wide surgical local
      excision is however recommended as the most important therapeutic intervention.
      We report a case of a HIV-infected man who developed a voluminous pelvic BLT
      which disappeared progressively under antiretroviral therapy with no additional
      treatment, contemporary to an improvement of his immunity, highlighting the
      possible spontaneous reversibility of HPV-induced tumours in treated HIV
      infection.

PMID- 27872137
TI  - Never forget basics.

PMID- 27872136
TI  - Vascular compression of left renal vein: the nutcracker phenomenon.

PMID- 27872139
TI  - Microsatellite instability evaluation by automated microfluidic electrophoresis:
      an update.

PMID- 27872140
TI  - Primary cilia are increased in number and demonstrate structural abnormalities in
      human cancer.
AB  - AIMS: Primary cilia play an important role in the regulation of cell signalling
      pathways and are thought to have a role in cancer but have seldom been studied in
      human cancer samples. METHODS: Primary cilia were visualised by dual
      immunofluorescence for anti-CROCC (ciliary rootlet coiled-coil) and anti-tubulin
      in a range of human cancers (including carcinomas of stomach, pancreas, prostate,
      lung and colon, lobular and ductal breast cancers and follicular lymphoma) and in
      matched normal tissue (stomach, pancreas, lung, large and small intestines,
      breast and reactive lymph nodes) samples using a tissue microarray; their
      frequency, association with proliferation, was measured by Ki-67 staining and
      their structure was analysed. RESULTS: Compared with normal tissues, primary
      cilia frequency was significantly elevated in adenocarcinoma of the lung (2.75%
      vs 1.85%, p=0.016), adenocarcinoma of the colon (3.80% vs 2.43%, respectively,
      p=0.017), follicular lymphoma (1.18% vs 0.83%, p=0.003) and pancreatic
      adenocarcinoma (7.00% vs 5.26%, p=0.002); there was no statistically significant
      difference compared with normal control tissue for gastric and prostatic
      adenocarcinomas or for lobular and ductal breast cancers. Additionally,
      structural abnormalities of primary cilia were identified in cancer tissues,
      including elongation of the axoneme, multiple basal bodies and branching of the
      axoneme. Ki-67 scores ranged from 0.7% to 78.4% and showed no statistically
      significant correlation with primary cilia frequency across all tissues
      (p=0.1501). CONCLUSIONS: The results show upregulation of primary cilia and the
      presence of structural defects in a wide range of human cancer tissue samples
      demonstrating association of dysregulation of primary cilia with human cancer.

PMID- 27872141
TI  - Differential roles of RET isoforms in medullary and papillary thyroid carcinomas.
AB  - The RET receptor tyrosine kinase mediates cell proliferation, survival and
      migration in embryogenesis and is implicated in the transformation and tumour
      progression in multiple cancers. RET is frequently mutated and constitutively
      activated in familial and sporadic thyroid carcinomas. As a result of alternative
      splicing, RET is expressed as two protein isoforms, RET9 and RET51, which differ
      in their unique C-terminal amino acids. These isoforms have distinct
      intracellular trafficking and associated signalling complexes, but functional
      differences are not well defined. We used shRNA-mediated knockdown (KD) of
      individual RET isoforms or of total RET to evaluate their functional
      contributions in thyroid carcinoma cells. We showed that RET is required for cell
      survival in medullary (MTC) but not papillary thyroid carcinoma (PTC) cells. In
      PTC cells, RET depletion reduced cell migration and induced a flattened
      epithelial-like morphology. RET KD decreased the expression of mesenchymal
      markers and matrix metalloproteinases and reduced anoikis resistance and invasive
      potential. Further, we showed that RET51 depletion had significantly greater
      effects on each of these processes than RET9 depletion in both MTC and PTC cells.
      Finally, we showed that expression of RET, particularly RET51, was correlated
      with malignancy in a panel of human thyroid tumour tissues. Together, our data
      show that RET expression promotes a more mesenchymal phenotype with reduced cell
      cell adhesion and increased invasiveness in PTC cell models, but is more
      important for tumour cell survival, proliferation and anoikis resistance in MTC
      models. Our data suggest that the RET51 isoform plays a more prominent role in
      mediating these processes compared to RET9.

PMID- 27872138
TI  - MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy.
AB  - Macropinocytosis, by which cells ingest large amounts of fluid, and autophagy,
      the lysosome-based catabolic process, involve vesicular biogenesis (early stage)
      and turnover (end stage). Much is known about early-stage events; however, our
      understanding of how the end stages of these processes are governed is
      incomplete. Here we demonstrate that the microRNA-103/107(miR-103/107) family,
      which is preferentially expressed in the stem cell-enriched limbal epithelium,
      coordinately regulates aspects of both these activities. Loss of miR-103/107
      causes dysregulation of macropinocytosis with the formation of large vacuoles,
      primarily through up-regulation of Src, Ras, and Ankfy1. Vacuole accumulation is
      not a malfunction of early-stage autophagy; rather, miR-103/107 ensure proper end
      stage autophagy by regulating diacylglycerol/protein kinase C and cyclin
      dependent kinase 5 signaling, which enables dynamin to function in vacuole
      clearance. Our findings unveil a key biological function for miR-103/107 in
      coordinately suppressing macropinocytosis and preserving end-stage autophagy,
      thereby contributing to maintenance of a stem cell-enriched epithelium.

PMID- 27872143
TI  - Authors' response: 'Predictors of patient satisfaction in an emergency care
      centre in central Saudi Arabia: a prospective study'.

PMID- 27872142
TI  - Cohesin acetylation and Wapl-Pds5 oppositely regulate translocation of cohesin
      along DNA.
AB  - Cohesin is a ring-shaped protein complex that plays a crucial role in sister
      chromatid cohesion and gene expression. The dynamic association of cohesin with
      chromatin is essential for these functions. However, the exact nature of cohesin
      dynamics, particularly cohesin translocation, remains unclear. We evaluated the
      dynamics of individual cohesin molecules on DNA and found that the cohesin core
      complex possesses an intrinsic ability to traverse DNA in an adenosine
      triphosphatase (ATPase)-dependent manner. Translocation ability is suppressed in
      the presence of Wapl-Pds5 and Sororin; this suppression is alleviated by the
      acetylation of cohesin and the action of mitotic kinases. In Xenopus laevis egg
      extracts, cohesin is translocated on unreplicated DNA in an ATPase- and Smc3
      acetylation-dependent manner. Cohesin movement changes from bidirectional to
      unidirectional when cohesin faces DNA replication; otherwise, it is incorporated
      into replicating DNA without being translocated or is dissociated from
      replicating DNA This study provides insight into the nature of individual cohesin
      dynamics and the mechanisms by which cohesin achieves cohesion in different
      chromatin contexts.

PMID- 27872145
TI  - Aspects of disaster research ethics applicable to other contexts.
AB  - In his article 'The Ebola Clinical Trials: a precedent for research ethics in
      disasters', Philippe Calain constructs a compelling case as to why and how
      experiences from the recent Ebola epidemic should be used to develop a framework
      for disaster research ethics. In particular, Calain proposes a useful model for
      assessing whether or not an unproven intervention could be suitable for human use
      in a disaster context, and makes a powerful argument against the separation of
      patient care from research goals. In this commentary, I argue that the separation
      of patient care goals from research goals is also unhelpful in the context of
      other forms of participant disadvantage even when that disadvantage is less
      severe than an ongoing public health emergency. I contend that recognising that
      research in disadvantaged populations is an intervention that could and should
      aim to produce positive outcomes for participants, just as it should in disaster
      contexts, therefore seems a well-justified lesson that can be extrapolated from
      the experience of the Ebola epidemic.

PMID- 27872144
TI  - Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent
      pathway.
AB  - The 1-deoxysphingolipids (1-deoxySLs) are atypical sphingolipids (SLs) that are
      formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine
      instead of serine during SL synthesis. The 1-deoxySLs are toxic to neurons and
      pancreatic beta-cells. Pathologically elevated 1-deoxySLs cause the inherited
      neuropathy, hereditary sensory autonomic neuropathy type 1 (HSAN1), and are also
      found in T2D. Diabetic sensory polyneuropathy (DSN) and HSAN1 are clinically very
      similar, suggesting that 1-deoxySLs may be implicated in both pathologies. The 1
      deoxySLs are considered to be dead-end metabolites, as they lack the C1-hydroxyl
      group, which is essential for the canonical degradation of SLs. Here, we report a
      previously unknown metabolic pathway, which is capable of degrading 1-deoxySLs.
      Using a variety of metabolic labeling approaches and high-resolution high
      accuracy MS, we identified eight 1-deoxySL downstream metabolites, which appear
      to be formed by cytochrome P450 (CYP)4F enzymes. Comprehensive inhibition and
      induction of CYP4F enzymes blocked and stimulated, respectively, the formation of
      the downstream metabolites. Consequently, CYP4F enzymes might be novel
      therapeutic targets for the treatment of HSAN1 and DSN, as well as for the
      prevention of T2D.

PMID- 27872146
TI  - Organic Anion Transporter 2: An Enigmatic Human Solute Carrier.
AB  - As a member of the solute carrier 22A (SLC22A) family, organic anion transporter
      2 (OAT2; SLC22A7) is emerging as an important drug transporter because of its
      expression in both the liver and kidney, two major eliminating organs, and its
      ability to transport not only a wide variety of xenobiotics but also numerous
      physiologically important endogenous compounds, like creatinine and cGMP.
      However, OAT2 has received relatively little attention compared with other OATs
      and solute carriers (SLCs), like organic cation transporters, sodium-dependent
      taurocholate cotransporting polypeptide, multidrug and toxin extrusion proteins,
      and organic anion-transporting polypeptides. Overall, the literature describing
      OAT2 is rapidly evolving, with numerous publications contradicting each other
      regarding the transport mechanism, tissue distribution, and transport of
      creatinine and cGMP, two important endogenous OAT2 substrates. Despite its status
      as a liver and kidney SLC, tools for assessing its activity and inhibition are
      lacking, and its role in drug disposition and elimination remains to be defined.
      The current review focuses on the available and emerging literature describing
      OAT2. We envision that OAT2 will gain more prominence as its expression,
      substrate, and inhibitor profile is investigated further and compared with other
      SLCs.

PMID- 27872147
TI  - Primary Human and Rat beta-Cells Release the Intracellular Autoantigens GAD65, IA
      2, and Proinsulin in Exosomes Together With Cytokine-Induced Enhancers of
      Immunity.
AB  - The target autoantigens in several organ-specific autoimmune diseases, including
      type 1 diabetes (T1D), are intracellular membrane proteins, whose initial
      encounter with the immune system is poorly understood. Here we propose a new
      model for how these proteins can initiate autoimmunity. We found that rat and
      human pancreatic islets release the intracellular beta-cell autoantigens in human
      T1D, GAD65, IA-2, and proinsulin in exosomes, which are taken up by and activate
      dendritic cells. Accordingly, the anchoring of GAD65 to exosome-mimetic liposomes
      strongly boosted antigen presentation and T-cell activation in the context of the
      human T1D susceptibility haplotype HLA-DR4. Cytokine-induced endoplasmic
      reticulum stress enhanced exosome secretion by beta-cells; induced exosomal
      release of the immunostimulatory chaperones calreticulin, Gp96, and ORP150; and
      increased exosomal stimulation of antigen-presenting cells. We propose that
      stress-induced exosomal release of intracellular autoantigens and
      immunostimulatory chaperones may play a role in the initiation of autoimmune
      responses in T1D.

PMID- 27872148
TI  - Proteomics Screen Identifies Class I Rab11 Family Interacting Proteins as Key
      Regulators of Cytokinesis.
AB  - The 14-3-3 protein family orchestrates a complex network of molecular
      interactions that regulates various biological processes. Owing to their role in
      regulating the cell cycle and protein trafficking, 14-3-3 proteins are prevalent
      in human diseases such as cancer, diabetes, and neurodegeneration. 14-3-3
      proteins are expressed in all eukaryotic cells, suggesting that they mediate
      their biological functions through evolutionarily conserved protein interactions.
      To identify these core 14-3-3 client proteins, we used an affinity-based
      proteomics approach to characterize and compare the human and Drosophila 14-3-3
      interactomes. Using this approach, we identified a group of Rab11 effector
      proteins, termed class I Rab11 family interacting proteins (Rab11-FIPs), or Rip11
      in Drosophila We found that 14-3-3 binds to Rip11 in a phospho-dependent manner
      to ensure its proper subcellular distribution during cell division. Our results
      indicate that Rip11 plays an essential role in the regulation of cytokinesis and
      that this function requires its association with 14-3-3 but not with Rab11.
      Together, our results suggest an evolutionarily conserved role for 14-3-3 in
      controlling Rip11-dependent protein transport during cytokinesis.

PMID- 27872150
TI  - The prognostic role of stress echocardiography in a contemporary population and
      the clinical significance of limited apical ischaemia.
AB  - INTRODUCTION: In this study, we aim to reassess the prognostic value of stress
      echocardiography (SE) in a contemporary population and to evaluate the clinical
      significance of limited apical ischaemia, which has not been previously studied.
      METHODS: We included 880 patients who underwent SE. Follow-up data with regards
      to MACCE (cardiac death, myocardial infarction, any repeat revascularisation and
      cerebrovascular accident) were collected over 12 months after the SE. Mortality
      data were recorded over 27.02 +/- 4.6 months (5.5-34.2 months). We sought to
      investigate the predictors of MACCE and all-cause mortality. RESULTS: In a
      multivariable analysis, only the positive result of SE was predictive of MACCE
      (HR, 3.71; P = 0.012). The positive SE group was divided into 2 subgroups: (a)
      inducible ischaemia limited to the apical segments ('apical ischaemia') and (b)
      ischaemia in any other segments with or without apical involvement ('other
      positive'). The subgroup of patients with apical ischaemia had a significantly
      worse outcome compared to the patients with a negative SE (HR, 3.68; P = 0.041)
      but a similar outcome to the 'other positive' subgroup. However, when
      investigated with invasive coronary angiography, the prevalence of coronary
      artery disease (CAD) and their rate of revascularisation was considerably lower.
      Only age (HR, 1.07; P < 0.001) was correlated with all-cause mortality.
      CONCLUSION: SE remains a strong predictor of patients' outcome in a contemporary
      population. A positive SE result was the only predictor of 12-month MACCE. The
      subgroup of patients with limited apical ischaemia have similar outcome to
      patients with ischaemia in other segments despite a lower prevalence of CAD and a
      lower revascularisation rate.

PMID- 27872149
TI  - Endogenous Telomerase Reverse Transcriptase N-Terminal Tagging Affects Human
      Telomerase Function at Telomeres In Vivo.
AB  - Telomerase action at telomeres is essential for the immortal phenotype of stem
      cells and the aberrant proliferative potential of cancer cells. Insufficient
      telomere maintenance can cause stem cell and tissue failure syndromes, while
      increased telomerase levels are associated with tumorigenesis. Both pathologies
      can arise from only small perturbation of telomerase function. To analyze
      telomerase at its low endogenous expression level, we genetically engineered
      human pluripotent stem cells (hPSCs) to express various N-terminal fusion
      proteins of the telomerase reverse transcriptase from its endogenous locus. Using
      this approach, we found that these modifications can perturb telomerase function
      in hPSCs and cancer cells, resulting in telomere length defects. Biochemical
      analysis suggests that this defect is multileveled, including changes in
      expression and activity. These findings highlight the unknown complexity of
      telomerase structural requirements for expression and function in vivo.

PMID- 27872151
TI  - Non-occupational physical activity levels of shift workers compared with non
      shift workers.
AB  - OBJECTIVES: Lack of physical activity (PA) has been hypothesised as an underlying
      mechanism in the adverse health effects of shift work. Therefore, our aim was to
      compare non-occupational PA levels between shift workers and non-shift workers.
      Furthermore, exposure-response relationships for frequency of night shifts and
      years of shift work regarding non-occupational PA levels were studied. METHODS:
      Data of 5980 non-shift workers and 532 shift workers from the European
      Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) were
      used in these cross-sectional analyses. Time spent (hours/week) in different PA
      types (walking/cycling/exercise/chores) and intensities (moderate/vigorous) were
      calculated based on self-reported PA. Furthermore, sports were operationalised
      as: playing sports (no/yes), individual versus non-individual sports, and non
      vigorous-intensity versus vigorous-intensity sports. PA levels were compared
      between shift workers and non-shift workers using Generalized Estimating
      Equations and logistic regression. RESULTS: Shift workers reported spending more
      time walking than non-shift workers (B=2.3 (95% CI 1.2 to 3.4)), but shift work
      was not associated with other PA types and any of the sports activities. Shift
      workers who worked 1-4 night shifts/month (B=2.4 (95% CI 0.6 to 4.3)) and >=5
      night shifts/month (B=3.7 (95% CI 1.8 to 5.6)) spent more time walking than non
      shift workers. No exposure-response relationships were found between years of
      shift work and PA levels. CONCLUSIONS: Shift workers spent more time walking than
      non-shift workers, but we observed no differences in other non-occupational PA
      levels. To better understand if and how PA plays a role in the negative health
      consequences of shift work, our findings need to be confirmed in future studies.

PMID- 27872154
TI  - Genetic determinants of myocardial dysfunction.
AB  - Heart failure (HF) is a major killer with high morbidity and mortality and nearly
      37.7 million people are affected by HF globally, making this a global epidemic.
      HF is a complex pathophysiological syndrome in which the mechanical function of
      heart for pumping blood is compromised. Cardiac structural and functional
      abnormalities culminate in decreased cardiac output along with increased
      intracardiac pressures under resting or stress conditions, leading to HF. Besides
      the acquired risk factors, the independent role of hereditary and genetic factors
      in the development, progression and prognosis of HF remains to be established.
      One of the most common causes of HF is cardiomyopathy and dilated cardiomyopathy
      and hypertrophic cardiomyopathy are the major forms, transmitted by autosomal
      dominant inheritance and often result from mutations in single or multiple genes,
      which predominantly code for proteins present in the cardiac sarcomere. Other
      inherited forms of cardiomyopathies that can trigger HF are metabolic and
      mitochondrial cardiomyopathies that result from mutations in proteins involved in
      fat or carbohydrate metabolism or mitochondrial biogenesis, affecting
      cardiomyocyte energy balance. Because of the inherent complications in the
      aetiology of HF, only a small number of genome-wide association studies (GWAS)
      could be conducted to identify SNPs in genes that are causally related to HF.
      Recent attempts to conduct GWAS in a focused approach on the HF risk factors led
      to identification of more SNPs. Initial attempts for gene therapy using adeno
      associated viral vectors have not been successful, but more studies are needed to
      understand the pathophysiological and genetic basis of HF.

PMID- 27872155
TI  - Glucose Concentrations of Less Than 3.0 mmol/L (54 mg/dL) Should Be Reported in
      Clinical Trials: A Joint Position Statement of the American Diabetes Association
      and the European Association for the Study of Diabetes.

PMID- 27872152
TI  - An unconventional interaction between Dis1/TOG and Mal3/EB1 in fission yeast
      promotes the fidelity of chromosome segregation.
AB  - Dynamic microtubule plus-ends interact with various intracellular target regions
      such as the cell cortex and the kinetochore. Two conserved families of
      microtubule plus-end-tracking proteins, the XMAP215, ch-TOG or CKAP5 family and
      the end-binding 1 (EB1, also known as MAPRE1) family, play pivotal roles in
      regulating microtubule dynamics. Here, we study the functional interplay between
      fission yeast Dis1, a member of the XMAP215/TOG family, and Mal3, an EB1 protein.
      Using an in vitro microscopy assay, we find that purified Dis1 autonomously
      tracks growing microtubule ends and is a bona fide microtubule polymerase. Mal3
      recruits additional Dis1 to microtubule ends, explaining the synergistic
      enhancement of microtubule dynamicity by these proteins. A non-canonical binding
      motif in Dis1 mediates the interaction with Mal3. X-ray crystallography shows
      that this new motif interacts in an unconventional configuration with the
      conserved hydrophobic cavity formed within the Mal3 C-terminal region that
      typically interacts with the canonical SXIP motif. Selectively perturbing the
      Mal3-Dis1 interaction in living cells demonstrates that it is important for
      accurate chromosome segregation. Whereas, in some metazoans, the interaction
      between EB1 and the XMAP215/TOG family members requires an additional binding
      partner, fission yeast relies on a direct interaction, indicating evolutionary
      plasticity of this critical interaction module.

PMID- 27872153
TI  - Xpf suppresses the mutagenic consequences of phagocytosis in Dictyostelium.
AB  - As time passes, mutations accumulate in the genomes of all living organisms.
      These changes promote genetic diversity, but also precipitate ageing and the
      initiation of cancer. Food is a common source of mutagens, but little is known
      about how nutritional factors cause lasting genetic changes in the consuming
      organism. Here, we describe an unusual genetic interaction between DNA repair in
      the unicellular amoeba Dictyostelium discoideum and its natural bacterial food
      source. We found that Dictyostelium deficient in the DNA repair nuclease Xpf (xpf
      ) display a severe and specific growth defect when feeding on bacteria. Despite
      being proficient in the phagocytosis and digestion of bacteria, over time, xpf-
      Dictyostelium feeding on bacteria cease to grow and in many instances die. The
      Xpf nuclease activity is required for sustained growth using a bacterial food
      source. Furthermore, the ingestion of this food source leads to a striking
      accumulation of mutations in the genome of xpf- Dictyostelium This work therefore
      establishes Dictyostelium as a model genetic system to dissect nutritional
      genotoxicity, providing insight into how phagocytosis can induce mutagenesis and
      compromise survival fitness.

PMID- 27872156
TI  - Association Between Blood Pressure and Adverse Renal Events in Type 1 Diabetes.
AB  - OBJECTIVE: To compare different blood pressure (BP) levels in their association
      with the risk of renal outcomes in type 1 diabetes and to determine whether an
      intensive glycemic control strategy modifies this association. RESEARCH DESIGN
      AND METHODS: We included 1,441 participants with type 1 diabetes between the ages
      of 13 and 39 years who had previously been randomized to receive intensive versus
      conventional glycemic control in the Diabetes Control and Complications Trial
      (DCCT). The exposures of interest were time-updated systolic BP (SBP) and
      diastolic BP (DBP) categories. Outcomes included macroalbuminuria (>300 mg/24 h)
      or stage III chronic kidney disease (CKD) (sustained estimated glomerular
      filtration rate <60 mL/min/1.73 m2). RESULTS: During a median follow-up time of
      24 years, there were 84 cases of stage III CKD and 169 cases of macroalbuminuria.
      In adjusted models, SBP in the <120 mmHg range was associated with a 0.59 times
      higher risk of macroalbuminuria (95% CI 0.37-0.95) and a 0.32 times higher risk
      of stage III CKD (95% CI 0.14-0.75) compared with SBPs between 130 and 140 mmHg.
      DBP in the <70 mmHg range were associated with a 0.73 times higher risk of
      macroalbuminuria (95% CI 0.44-1.18) and a 0.47 times higher risk of stage III CKD
      (95% CI 0.21-1.05) compared with DBPs between 80 and 90 mmHg. No interaction was
      noted between BP and prior DCCT-assigned glycemic control strategy (all P >
      0.05). CONCLUSIONS: A lower BP (<120/70 mmHg) was associated with a substantially
      lower risk of adverse renal outcomes, regardless of the prior assigned glycemic
      control strategy. Interventional trials may be useful to help determine whether
      the currently recommended BP target of 140/90 mmHg may be too high for optimal
      renal protection in type 1 diabetes.

PMID- 27872157
TI  - Exendin-4 increases oxygen consumption and thermogenic gene expression in muscle
      cells.
AB  - Glucagon-like peptide-1 (GLP1) has many anti-diabetic actions and also increases
      energy expenditure in vivo As skeletal muscle is a major organ controlling energy
      metabolism, we investigated whether GLP1 can affect energy metabolism in muscle.
      We found that treatment of differentiated C2C12 cells with exendin-4 (Ex-4), a
      GLP1 receptor agonist, reduced oleate:palmitate-induced lipid accumulation and
      triglyceride content compared with cells without Ex-4 treatment. When we examined
      the oxygen consumption rate (OCR), not only the basal OCR but also the OCR
      induced by oleate:palmitate addition was significantly increased in Ex-4-treated
      differentiated C2C12 cells, and this was inhibited by exendin-9, a GLP1 receptor
      antagonist. The expression of uncoupling protein 1 (UCP1), beta3-adrenergic
      receptor, peroxisome proliferator-activator receptor a (PPARa) and farnesoid X
      receptor mRNA was significantly upregulated in Ex-4-treated differentiated C2C12
      cells, and the upregulation of these mRNA was abolished by treatment with
      adenylate cyclase inhibitor (2'5'-dideoxyadenosine) or PKA inhibitor (H-89). As
      well, intramuscular injection of Ex-4 into diet-induced obese mice significantly
      increased the expression of UCP1, PPARa and p-AMPK in muscle. We suggest that
      exposure to GLP1 increases energy expenditure in muscle through the upregulation
      of fat oxidation and thermogenic gene expression, which may contribute to
      reducing obesity and insulin resistance.

PMID- 27872158
TI  - Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid
      tumors.
AB  - Parathyroid tumors display reduced sensitivity to extracellular calcium
      ([Ca2+]o). [Ca2+]o activates calcium-sensing receptor (CASR), which interacts
      with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1)
      the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA
      and protein expression, and (3) on ERK signaling activation, (4) the effect of
      the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist
      R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA
      immunostaining was variably reduced in parathyroid tumors. Immunofluorescence
      showed that FLNA localized in membrane and cytoplasm and co-localized with CASR
      in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment
      could also be detected in PAds nuclear protein fractions. In HEK293 cells
      transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA
      reduced CASR mRNA levels and total and membrane-associated CASR proteins. In
      agreement, FLNA mRNA levels positively correlated with CASR expression in a
      series of 74 PAds; however, any significant correlation with primary
      hyperparathyroidism severity could be detected and FLNA transcript levels did not
      differ between PAds harboring 990R or 990G CASR variants. R568 treatment was
      efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca2+]o in the
      absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and
      parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein
      expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in
      receptor expression, membrane localization and ERK signaling activation of both
      990R and 990G CASR variants.

PMID- 27872159
TI  - Intensive treatment of hypertension to a SBP <120 mm Hg in patients aged 75 and
      over reduces mortality and cardiovascular events.

PMID- 27872160
TI  - Periungual and Oral Verruca.

PMID- 27872162
TI  - Influence of two bulge loops on the stability of RNA duplexes.
AB  - Fifty-three RNA duplexes containing two single nucleotide bulge loops were
      optically melted in 1 M NaCl in order to determine the thermodynamic parameters
      DeltaH degrees , DeltaS degrees , DeltaG degrees 37, and TM for each duplex.
      Because of the large number of possible combinations and lack of sequence effects
      observed previously, we limited our initial investigation to adenosine bulges,
      the most common naturally occurring bulge. For example, the following duplexes
      were investigated: 5'GGCAXYAGGC/3'CCG YX CCG, 5'GGCAXY GCC/3'CCG YXACGG, and
      5'GGC XYAGCC/3'CCGAYX CGG. The identity of XY (where XY are Watson-Crick base
      pairs) and the total number of base pairs in the terminal and central stems were
      varied. As observed for duplexes with a single bulge loop, the effect of the two
      bulge loops on duplex stability is primarily influenced by non-nearest neighbor
      interactions. In particular, the stability of the stems influences the
      destabilization of the duplex by the inserted bulge loops. The model proposed to
      predict the influence of multiple bulge loops on duplex stability suggests that
      the destabilization of each bulge is related to the stability of the adjacent
      stems. A database of RNA secondary structures was examined to determine the
      naturally occurring abundance of duplexes containing multiple bulge loops. Of the
      2000 examples found in the database, over 65% of the two bulge loops occur within
      3 base pairs of each other. A database of RNA three-dimensional structures was
      examined to determine the structure of duplexes containing two single nucleotide
      bulge loops. The structures of the bulge loops are described.

PMID- 27872165
TI  - Change and Positive Organizational Scholarship.

PMID- 27872163
TI  - Role of autophagy in cadmium-induced testicular injury.
AB  - The testis is sensitive to cadmium, but studies investigating cadmium-induced
      testicular injury have not yet clearly revealed the underlying mechanisms. This
      study aimed to investigate the injurious effects of cadmium on rat testes and the
      role that autophagy plays in this process. Wistar rats were randomly divided into
      four groups and intraperitoneally injected with 0.2 (low), 0.4 (middle), and 0.8
      mg/kg.body weight (high) cadmium chloride for 5 weeks, while the control rats
      were injected with equal volume of saline. Rats exposed to cadmium appeared
      inactive and had reduced body weights and increased testicular organ coefficients
      at the end of treatment compared with control rats. Atomic absorption results
      showed that cadmium levels increased with increased cadmium exposure. Hematoxylin
      and eosin staining of testicular sections showed seminiferous tubular atrophy,
      decreased pipe diameter, spermatogonial stem cells falling off the inner lining,
      and reduced germ cell layers of disorderly arrangements in cadmium-treated rats.
      Immunohistochemical and western blot results both showed that levels of the
      autophagy-related proteins Beclin1 and microtubule-associated protein 1 light
      chain 3B (LC3B) increased with increased cadmium exposure. We also found that
      LC3B-II and calcium-sensing receptor (CSR) levels in cadmium-exposed rats
      significantly increased. By immunofluorescence, we found that the percentage of
      cells that expressed the CSR was significantly higher in LC3B-positive than LC3B
      negative cells. Together, our results showed that cadmium accumulates in the
      testes causing testicular injury, which may be related to increased autophagy
      levels. Furthermore, calcium disorders associated with the CSR may reveal a
      potential way to activate autophagy.

PMID- 27872161
TI  - Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic
      kidney disease.
AB  - In chronic kidney disease (CKD), the decline in the glomerular filtration rate is
      associated with increased morbidity and mortality and thus poses a major
      challenge for healthcare systems. While the contribution of tissue-derived miRNAs
      and mRNAs to CKD progression has been extensively studied, little is known about
      the role of urinary exosomes and their association with CKD. Exosomes are small,
      membrane-derived endocytic vesicles that contribute to cell-to-cell communication
      and are present in various body fluids, such as blood or urine. Next-generation
      sequencing approaches have revealed that exosomes are enriched in noncoding RNAs
      and thus exhibit great potential for sensitive nucleic acid biomarkers in various
      human diseases. Therefore, in this study we aimed to identify urinary exosomal
      ncRNAs as novel biomarkers for diagnosis of CKD. Since up to now most approaches
      have focused on the class of miRNAs, we extended our analysis to several other
      noncoding RNA classes, such as tRNAs, tRNA fragments (tRFs), mitochondrial tRNAs,
      or lincRNAs. For their computational identification from RNA-seq data, we
      developed a novel computational pipeline, designated as ncRNASeqScan. By these
      analyses, in CKD patients we identified 30 differentially expressed ncRNAs,
      derived from urinary exosomes, as suitable biomarkers for early diagnosis.
      Thereby, miRNA-181a appeared as the most robust and stable potential biomarker,
      being significantly decreased by about 200-fold in exosomes of CKD patients
      compared to healthy controls. Using a cell culture system for CKD indicated that
      urinary exosomes might indeed originate from renal proximal tubular epithelial
      cells.

PMID- 27872164
TI  - Functional consequences of B-repeat sequence variation in the staphylococcal
      biofilm protein Aap: deciphering the assembly code.
AB  - Staphylococcus epidermidis is an opportunistic pathogen that can form robust
      biofilms that render the bacteria resistant to antibiotic action and immune
      responses. Intercellular adhesion in S. epidermidis biofilms is mediated by the
      cell wall-associated accumulation-associated protein (Aap), via zinc-mediated
      self-assembly of its B-repeat region. This region contains up to 17 nearly
      identical sequence repeats, with each repeat assumed to be functionally
      equivalent. However, Aap B-repeats exist as two subtypes, defined by a cluster of
      consensus or variant amino acids. These variable residues are positioned near the
      zinc-binding (and dimerization) site and the stability determinant for the B
      repeat fold. We have characterized four B-repeat constructs to assess the
      functional relevance of the two Aap B-repeat subtypes. Analytical
      ultracentrifugation experiments demonstrated that constructs with the variant
      sequence show reduced or absent Zn2+-induced dimerization. Likewise, circular
      dichroism thermal denaturation experiments showed that the variant sequence could
      significantly stabilize the fold, depending on its location within the construct.
      Crystal structures of three of the constructs revealed that the side chains from
      the variant sequence form an extensive bonding network that can stabilize the
      fold. Furthermore, altered distribution of charged residues between consensus and
      variant sequences changes the electrostatic potential in the vicinity of the Zn2+
      binding site, providing a mechanistic explanation for the loss of zinc-induced
      dimerization in the variant constructs. These data suggest an assembly code that
      defines preferred oligomerization modes of the B-repeat region of Aap and a slip
      grip model for initial contact followed by firm intercellular adhesion during
      biofilm formation.

PMID- 27872167
TI  - The Use of Osteotomies in the Treatment of Asymmetric Ankle Joint Arthritis.

PMID- 27872166
TI  - Consistency of medical record reporting of a set of indicators for proactive
      palliative care in patients with chronic obstructive pulmonary disease.
AB  - To identify patients hospitalized for an acute exacerbation of chronic
      obstructive pulmonary disease (COPD) who have a poor prognosis and might benefit
      from proactive palliative care, a set of indicators had been developed from the
      literature. A patient is considered eligible for proactive palliative care when
      meeting >=2 criteria of the proposed set of 11 indicators. In order to develop a
      doctor-friendly and patient-convenient tool, our primary objective was to examine
      whether these indicators are documented consistently in the medical records.
      Besides, percentage of patients with a poor prognosis and prognostic value were
      explored. We conducted a retrospective medical record review of 33 patients. Five
      indicators; non-invasive ventilation (NIV), comorbidity, body mass index (BMI),
      previous admissions for acute exacerbation COPD and age were always documented.
      Three indicators; hypoxaemia and/or hypercapnia, professional home care and
      actual forced expiratory volume1% (FEV1%) were documented in more than half of
      the records, whereas the clinical COPD questionnaire (CCQ), medical research
      council dyspnoea (MRC dyspnoea) and the surprise question were never registered.
      Besides, 78.8% of the patients met >=2 criteria and there was a significant
      association between meeting >=2 criteria and mortality within 1 year (one-sided
      Fisher's exact test, p = 0.04). The set of indicators for proactive palliative
      care in patients with COPD appeared to be user-friendly and feasible.

PMID- 27872168
TI  - Accurate Carbohydrate Counting Is an Important Determinant of Postprandial
      Glycemia in Children and Adolescents With Type 1 Diabetes on Insulin Pump
      Therapy.
AB  - BACKGROUND: Carbohydrate (CHO) counting is a key nutritional intervention
      utilized in the management of diabetes to optimize postprandial glycemia. The aim
      of the study was to examine the impact of accuracy of CHO counting on the
      postprandial glucose in children and adolescents with type 1 diabetes on insulin
      pump therapy. METHODS: Children/adolescents with type 1 diabetes who were on
      insulin pump therapy for a minimum of 6 months are enrolled in the study.
      Patients were instructed to record details of meals consumed, estimated CHO count
      per meal, and 2-hour postprandial glucose readings over 3-5 days. Meals' CHO
      contents were recounted by an experienced clinical dietician, and those within
      20% of the dietician's counting were considered accurate. RESULTS: A total of 30
      patients (21 females) were enrolled. Age range (median) was 8-18 (SD 13) years.
      Data of 247 meals were analyzed. A total of 165 (67%) meals' CHO contents were
      accurately counted. Of those, 90 meals (55%) had in-target postprandial glucose (
      P < .000). There was an inverse relationship between inaccurate CHO estimates and
      postprandial glucose. Of the 63 underestimated meals, 55 had above-target
      glucose, while 12 of the 19 overestimated meals were followed by low glucose.
      There was no association between accuracy and meal size (Spearman's rho = .019).
      CONCLUSION: Accuracy of CHO counting is an important determining factor of
      postprandial glycemia. However, other factors should be considered when advising
      on prandial insulin calculation. Underestimation and overestimation of CHO result
      in postprandial hyperglycemia and hypoglycemia, respectively. Accuracy does not
      correlate with meal size.

PMID- 27872169
TI  - Myelopathy: chameleons and mimics.
AB  - The diagnosis of spinal cord disease may be delayed or missed if the presentation
      does not conform to the expected pattern of a symmetrical spastic paraparesis
      with sphincter dysfunction and a sensory level. This may occur when a myelopathy
      has yet to evolve fully, or is highly asymmetrical, as in Brown-Sequard syndrome.
      Other potential distractions include fluctuating symptoms, as may accompany
      spinal cord demyelination, and pseudoneuropathic features, as seen acutely in
      spinal shock and in the chronic setting with some high cervical cord lesions. A
      second pathology, such as a polyneuropathy or polyradiculopathy, can mask the
      presence of a myelopathy. The converse situation, of non-myelopathic disease
      mimicking a cord lesion, arises typically when symptoms and/or signs approximate
      bilateral symmetry. This may happen with certain diseases of the brain, or of the
      peripheral nerves, with functional disorders and even occasionally with non
      neurological disease. These sources of diagnostic difficulty assume clinical
      importance when they delay the recognition of conditions that require urgent
      treatment.

PMID- 27872170
TI  - Spinal cord infarction after cocaine use.

PMID- 27872171
TI  - Organelles in health and diseases.

PMID- 27872172
TI  - Urea, a true uremic toxin: the empire strikes back.
AB  - Blood levels of urea rise with progressive decline in kidney function. Older
      studies examining acute urea infusion suggested that urea was well-tolerated at
      levels 8-10* above normal values. More recent in vitro and in vivo work argue the
      opposite and demonstrate both direct and indirect toxicities of urea, which
      probably promote the premature aging phenotype that is pervasive in chronic
      kidney disease (CKD). Elevated urea at concentrations typically encountered in
      uremic patients induces disintegration of the gut epithelial barrier, leading to
      translocation of bacterial toxins into the bloodstream and systemic inflammation.
      Urea induces apoptosis of vascular smooth muscle cells as well as endothelial
      dysfunction, thus directly promoting cardiovascular disease. Further, urea
      stimulates oxidative stress and dysfunction in adipocytes, leading to insulin
      resistance. Finally, there are widespread indirect effects of elevated urea as a
      result of the carbamylation reaction, where isocyanic acid (a product of urea
      catabolism) alters the structure and function of proteins in the body.
      Carbamylation has been linked with renal fibrosis, atherosclerosis and anaemia.
      In summary, urea is a re-emerging Dark Force in CKD pathophysiology. Trials
      examining low protein diet to minimize accumulation of urea and other toxins
      suggest a clinical benefit in terms of slowing progression of CKD.

PMID- 27872173
TI  - Medical morbidity and mortality conferences: past, present and future.
AB  - Morbidity and mortality conferences (MMCs) have three potential aims-to improve
      patient safety by reducing adverse events and preventable deaths, to improve
      overall quality of care as part of the hospital governance structure and as
      educational learning events. At present, medical MMCs vary widely in format and
      attendance from hospital to hospital. The evidence for MMCs actually reducing
      adverse events and preventing avoidable deaths is disappointing. There is better
      evidence for their educational role. The majority of medical deaths in hospitals
      are frail older people with poor life expectancy in whom inadequate care is more
      likely to be due to errors of omission rather than commission. Medical MMCs
      should be multidisciplinary and led by a senior clinician to encourage discussion
      and reflection in a 'blame-free' environment. They should be learning events for
      both clinicians and the organisation as a whole with a structure to support this.

PMID- 27872174
TI  - The emergence of a new specialty of oncocardiology.

PMID- 27872175
TI  - Court in judgement of informed consent.

PMID- 27872176
TI  - The evolving landscape of combination therapy for pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressively fatal disease, and the
      goal in treatment is to prevent disease progression. The standard of care often
      involves medications from multiple therapeutic classes, and there has been
      significant interest both in the choice of agent as well as the timing of
      initiation. There is a growing body of support for starting multiple medications
      at the time of diagnosis, or 'upfront ', rather than using sequential addition to
      prevent clinical deterioration.

PMID- 27872177
TI  - Levetiracetam for the Treatment of Seizures in Neonatal Hypoxic Ischemic
      Encephalopathy.
AB  - The objective of this study was to determine the efficacy and safety of
      levetiracetam in treatment of neonatal seizures due to hypoxic ischemic
      encephalopathy. Seizures often persist in neonates with hypoxic ischemic
      encephalopathy despite phenobarbital. A retrospective single-center study was
      conducted in neonates >=36 weeks gestation with hypoxic ischemic encephalopathy.
      A total of 127 neonates were identified born 2008-2015. Clinical seizures
      occurred in 83 infants. Fifty-one neonates (61%) had cessation of seizures with
      only phenobarbital. Thirty-two neonates received levetiracetam after
      phenobarbital, and the seizures stopped in 27 of these neonates. The mean total
      loading dose of levetiracetam was 63 mg/kg. Mean maintenance dose of
      levetiracetam was 65 mg/kg/d. We found no negative side effects in neonates
      following levetiracetam use. Our study finds that levetiracetam is an efficacious
      medication in treatment of seizures in the setting of neonatal hypoxic ischemic
      encephalopathy. Future prospective studies should explore its use as a first-line
      medication.

PMID- 27872178
TI  - Childhood Activity on Progression in Limb Girdle Muscular Dystrophy 2I.
AB  - Limb girdle muscular dystrophy 2I is a slowly progressive muscular dystrophy due
      to mutations in the Fukutin-related protein ( FKRP) gene. Clinicians are
      frequently asked if physical activity is harmful for pediatric patients with limb
      girdle muscular dystrophy 2I. The primary objective of this study was to
      determine if there is a relationship between self-reported childhood activity
      level and motor function and respiratory function in older children and adults
      with limb girdle muscular dystrophy 2I. We compared retrospective self-reported
      middle school activity level and sport participation with age at onset of
      weakness, 10-meter walk test, and forced vital capacity later in life in 41
      participants with FKRP mutations. We found no relationship between activity level
      in childhood and disease course later in life, suggesting that self-directed
      physical activity in children with limb girdle muscular dystrophy 2I does not
      negatively affect disease progression and outcome.

PMID- 27872179
TI  - Anti- N-Methyl-d-Aspartate (NMDA) Receptor Encephalitis.
AB  - Anti- N-methyl-d-aspartate receptor (NMDAR) encephalitis has been shown to be a
      treatable form of autoimmune encephalitis, but there remains no standardized
      approach to immunotherapy. We designed an anonymous survey sent to members of the
      Child Neurology Society to identify the current practices among child
      neurologists. A total of 151 pediatric neurologists responded to the survey. With
      these responses we were able to highlight areas of practice uniformity, including
      first-line treatment with intravenous immunoglobulin and intravenous
      methylprednisone and initiation of disease-modifying therapy with rituximab
      alone. The survey also identifies existing gaps in knowledge, specifically, when
      to add disease-modifying therapy and how long to continue therapy. We propose
      that the areas of agreement can be used as a step toward establishing standard
      treatment guidelines and research protocols directed at evidence-based clinical
      trials.

PMID- 27872180
TI  - On Learning Natural-Science Categories That Violate the Family-Resemblance
      Principle.
AB  - The general view in psychological science is that natural categories obey a
      coherent, family-resemblance principle. In this investigation, we documented an
      example of an important exception to this principle: Results of a
      multidimensional-scaling study of igneous, metamorphic, and sedimentary rocks
      (Experiment 1) suggested that the structure of these categories is disorganized
      and dispersed. This finding motivated us to explore what might be the optimal
      procedures for teaching dispersed categories, a goal that is likely critical to
      science education in general. Subjects in Experiment 2 learned to classify
      pictures of rocks into compact or dispersed high-level categories. One group
      learned the categories through focused high-level training, whereas a second
      group was required to simultaneously learn classifications at a subtype level.
      Although high-level training led to enhanced performance when the categories were
      compact, subtype training was better when the categories were dispersed. We
      provide an interpretation of the results in terms of an exemplar-memory model of
      category learning.

PMID- 27872181
TI  - Action Experience Drives Visual-Processing Biases Near the Hands.
AB  - Observers experience affordance-specific biases in visual processing for objects
      within the hands' grasping space, but the mechanism that tunes visual cognition
      to facilitate action remains unknown. I investigated the hypothesis that altered
      vision near the hands is a result of experience-driven plasticity. Participants
      performed motion-detection and form-perception tasks-while their hands were
      either near the display, in atypical grasping postures, or positioned in their
      laps-both before and after learning novel grasp affordances. Participants showed
      enhanced temporal sensitivity for stimuli viewed near the backs of the hands
      after training to execute a power grasp using the backs of their hands
      (Experiment 1), but showed enhanced spatial sensitivity for stimuli viewed near
      the tips of their little fingers after training to use their little fingers to
      execute a precision grasp (Experiment 2). These results show that visual biases
      near the hands are plastic, facilitating processing of information relevant to
      learned grasp affordances.

PMID- 27872182
TI  - An ompR-envZ Two-Component System Ortholog Regulates Phase Variation, Osmotic
      Tolerance, Motility, and Virulence in Acinetobacter baumannii Strain AB5075.
AB  - Recently, a novel phase-variable colony opacity phenotype was discovered in
      Acinetobacter baumannii strain AB5075, where colonies interconvert between opaque
      and translucent variants. Opaque colonies become mottled or sectored after 24 h
      of growth due to translucent variants arising within the colony. This easily
      distinguishable opaque-colony phenotype was used to screen for random transposon
      insertions that increased the frequency of sectoring at a time point when wild
      type colonies were uniformly opaque. A colony was identified that contained
      multiple papillae of translucent variants, and the insertion in this mutant
      mapped to an ortholog of the two-component system response regulator ompR
      Subsequent investigation of in-frame deletions of ompR and the sensor kinase envZ
      (located adjacent to ompR) showed that the switching frequency from opaque to
      translucent was increased 401- and 281-fold, respectively. The ompR mutant also
      exhibited sensitivity to sodium chloride in growth medium, whereas the envZ
      mutation did not elicit sensitivity to sodium chloride. Mutation of either gene
      reduced motility in A. baumannii strain AB5075, but a mutation in both ompR and
      envZ produced a more profound effect. The ompR and envZ genes were cotranscribed
      but were not subject to autoregulation by OmpR. Both ompR and envZ mutant opaque
      variants were attenuated in virulence in the Galleria mellonella infection model,
      whereas mutation of ompR had no effect on the virulence of the translucent
      variant. IMPORTANCEAcinetobacter baumannii is a well-known antibiotic-resistant
      pathogen; many clinical isolates can only be treated by a very small number of
      antibiotics (including colistin), while some exhibit panresistance. The current
      antimicrobial arsenal is nearing futility in the treatment of Acinetobacter
      infections, and new avenues of treatment are profoundly needed. Since phase
      variation controls the transition between opaque (virulent) and translucent
      (avirulent) states in A. baumannii, this may represent an "Achilles' heel" that
      can be targeted via the development of small molecules that lock cells in the
      translucent state and allow the host immune system to clear the infection. A
      better understanding of how phase variation is regulated may allow for the
      development of methods to target this process. The ompR-envZ two-component system
      ortholog negatively regulates phase variation in A. baumannii, and perturbation
      of this system leads to the attenuation of virulence in an invertebrate infection
      model.

PMID- 27872183
TI  - Roles of the Essential Protein FtsA in Cell Growth and Division in Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae is an ovoid-shaped Gram-positive bacterium that grows by
      carrying out peripheral and septal peptidoglycan (PG) synthesis, analogous to
      model bacilli, such as Escherichia coli and Bacillus subtilis In the model
      bacilli, FtsZ and FtsA proteins assemble into a ring at midcell and are dedicated
      to septal PG synthesis but not peripheral PG synthesis; hence, inactivation of
      FtsZ or FtsA results in long filamentous cells unable to divide. Here, we
      demonstrate that FtsA and FtsZ colocalize at midcell in S. pneumoniae and that
      partial depletion of FtsA perturbs septum synthesis, resulting in elongated cells
      with multiple FtsZ rings that fail to complete septation. Unexpectedly, complete
      depletion of FtsA resulted in the delocalization of FtsZ rings and ultimately
      cell ballooning and lysis. In contrast, depletion or deletion of gpsB and sepF,
      which in B. subtilis are synthetically lethal with ftsA, resulted in enlarged and
      elongated cells with multiple FtsZ rings, with deletion of sepF mimicking partial
      depletion of FtsA. Notably, cell ballooning was not observed, consistent with
      later recruitment of these proteins to midcell after Z-ring assembly. The
      overproduction of FtsA stimulates septation and suppresses the cell division
      defects caused by the deletion of sepF and gpsB under some conditions, supporting
      the notion that FtsA shares overlapping functions with GpsB and SepF at later
      steps in the division process. Our results indicate that, in S. pneumoniae, both
      GpsB and SepF are involved in septal PG synthesis, whereas FtsA and FtsZ
      coordinate both peripheral and septal PG synthesis and are codependent for
      localization at midcell.IMPORTANCEStreptococcus pneumoniae (pneumococcus) is a
      clinically important human pathogen for which more therapies against unexploited
      essential targets, like cell growth and division proteins, are needed.
      Pneumococcus is an ovoid-shaped Gram-positive bacterium with cell growth and
      division properties that have important distinctions from those of rod-shaped
      bacteria. Gaining insights into these processes can thus provide valuable
      information to develop novel antimicrobials. Whereas rods use distinctly
      localized protein machines at different cellular locations to synthesize
      peripheral and septal peptidoglycans, we present evidence that S. pneumoniae
      organizes these two machines at a single location in the middle of dividing
      cells. Here, we focus on the properties of the actin-like protein FtsA as an
      essential orchestrator of peripheral and septal growth in this bacterium.

PMID- 27872184
TI  - Functional variants in the sucrase-isomaltase gene associate with increased risk
      of irritable bowel syndrome.
AB  - OBJECTIVE: IBS is a common gut disorder of uncertain pathogenesis. Among other
      factors, genetics and certain foods are proposed to contribute. Congenital
      sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide
      malabsorption characterised by diarrhoea, abdominal pain and bloating, which are
      features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their
      potential relevance in IBS. DESIGN: We sequenced SI exons in seven familial
      cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter
      and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a
      multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val
      to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in
      relation to IBS status, stool frequency and faecal microbiota composition in 250
      individuals from the general population. RESULTS: CSID mutations were more common
      in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation
      Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected
      in 6/7 sequenced familial cases, and increased IBS risk in case-control and
      population-based cohorts, with best evidence for diarrhoea phenotypes (combined
      p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage
      correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota
      abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic
      activity in vitro compared with 15Val (p<0.05). CONCLUSIONS: SI gene variants
      coding for disaccharidases with defective or reduced enzymatic activity
      predispose to IBS. This may help the identification of individuals at risk, and
      contribute to personalising treatment options in a subset of patients.

PMID- 27872185
TI  - The Major Replicative Histone Chaperone CAF-1 Suppresses the Activity of the DNA
      Mismatch Repair System in the Cytotoxic Response to a DNA-methylating Agent.
AB  - The DNA mismatch repair (MMR) system corrects DNA mismatches in the genome. It is
      also required for the cytotoxic response of O6-methylguanine-DNA
      methyltransferase (MGMT)-deficient mammalian cells and yeast mgt1Delta rad52Delta
      cells to treatment with Sn1-type methylating agents, which produce cytotoxic O6
      methylguanine (O6-mG) DNA lesions. Specifically, an activity of the MMR system
      causes degradation of irreparable O6-mG-T mispair-containing DNA, triggering cell
      death; this process forms the basis of treatments of MGMT-deficient cancers with
      Sn1-type methylating drugs. Recent research supports the view that degradation of
      irreparable O6-mG-T mispair-containing DNA by the MMR system and CAF-1-dependent
      packaging of the newly replicated DNA into nucleosomes are two concomitant
      processes that interact with each other. Here, we studied whether CAF-1 modulates
      the activity of the MMR system in the cytotoxic response to Sn1-type methylating
      agents. We found that CAF-1 suppresses the activity of the MMR system in the
      cytotoxic response of yeast mgt1Delta rad52Delta cells to the prototypic Sn1-type
      methylating agent N-methyl-N'-nitro-N-nitrosoguanidine. We also report evidence
      that in human MGMT-deficient cell-free extracts, CAF-1-dependent packaging of
      irreparable O6-mG-T mispair-containing DNA into nucleosomes suppresses its
      degradation by the MMR system. Taken together, these findings suggest that CAF-1
      dependent incorporation of irreparable O6-mG-T mispair-containing DNA into
      nucleosomes suppresses its degradation by the MMR system, thereby defending the
      cell against killing by the Sn1-type methylating agent.

PMID- 27872186
TI  - The Interplay between Calmodulin and Membrane Interactions with the Pleckstrin
      Homology Domain of Akt.
AB  - The Akt protein, a serine/threonine kinase, plays important roles in cell
      survival, apoptosis, and oncogenes. Akt is translocated to the plasma membrane
      for activation. Akt-membrane binding is mediated by direct interactions between
      its pleckstrin homology domain (PHD) and phosphatidylinositol 3,4,5-trisphosphate
      (PI(3,4,5)P3). It has been shown that Akt activation in breast cancer cells is
      modulated by calmodulin (CaM). However, the molecular mechanism of the interplay
      between CaM and membrane binding is not established. Here, we employed nuclear
      magnetic resonance (NMR) and biochemical and biophysical techniques to
      characterize how PI(3,4,5)P3, CaM, and membrane mimetics (nanodisc) bind to
      Akt(PHD). We show that PI(3,4,5)P3 binding to Akt(PHD) displaces the C-terminal
      lobe of CaM but not the weakly binding N-terminal lobe. However, binding of a
      PI(3,4,5)P3-embedded membrane nanodisc to Akt(PHD) with a 103-fold tighter
      affinity than PI(3,4,5)P3 is able to completely displace CaM. We also show that
      Akt(PHD) binds to both layers of the nanodisc, indicating proper incorporation of
      PI(3,4,5)P3 on the nanodisc surface. No detectable binding has been observed
      between Akt(PHD) and PI(3,4,5)P3-free nanodiscs, demonstrating that PI(3,4,5)P3
      is required for membrane binding, CaM displacement, and Akt activation. Using
      pancreatic cancer cells, we demonstrate that inhibition of Akt-CaM binding
      attenuated Akt activation. Our findings support a model by which CaM binds to Akt
      to facilitate its translocation to the membrane. Elucidation of the molecular
      details of the interplay between membrane and CaM binding to Akt may help in the
      development of potential targets to control the pathophysiological processes of
      cell survival.

PMID- 27872187
TI  - Galactomannan Catabolism Conferred by a Polysaccharide Utilization Locus of
      Bacteroides ovatus: ENZYME SYNERGY AND CRYSTAL STRUCTURE OF A beta-MANNANASE.
AB  - A recently identified polysaccharide utilization locus (PUL) from Bacteroides
      ovatus ATCC 8483 is transcriptionally up-regulated during growth on galacto- and
      glucomannans. It encodes two glycoside hydrolase family 26 (GH26) beta
      mannanases, BoMan26A and BoMan26B, and a GH36 alpha-galactosidase, BoGal36A. The
      PUL also includes two glycan-binding proteins, confirmed by beta-mannan affinity
      electrophoresis. When this PUL was deleted, B. ovatus was no longer able to grow
      on locust bean galactomannan. BoMan26A primarily formed mannobiose from mannan
      polysaccharides. BoMan26B had higher activity on galactomannan with a high degree
      of galactosyl substitution and was shown to be endo-acting generating a more
      diverse mixture of oligosaccharides, including mannobiose. Of the two beta
      mannanases, only BoMan26B hydrolyzed galactoglucomannan. A crystal structure of
      BoMan26A revealed a similar structure to the exo-mannobiohydrolase CjMan26C from
      Cellvibrio japonicus, with a conserved glycone region (-1 and -2 subsites),
      including a conserved loop closing the active site beyond subsite -2. Analysis of
      cellular location by immunolabeling and fluorescence microscopy suggests that
      BoMan26B is surface-exposed and associated with the outer membrane, although
      BoMan26A and BoGal36A are likely periplasmic. In light of the cellular location
      and the biochemical properties of the two characterized beta-mannanases, we
      propose a scheme of sequential action by the glycoside hydrolases encoded by the
      beta-mannan PUL and involved in the beta-mannan utilization pathway in B. ovatus.
      The outer membrane-associated BoMan26B initially acts on the polysaccharide
      galactomannan, producing comparably large oligosaccharide fragments. Galactomanno
      oligosaccharides are further processed in the periplasm, degalactosylated by
      BoGal36A, and subsequently hydrolyzed into mainly mannobiose by the beta
      mannanase BoMan26A.

PMID- 27872188
TI  - A Monoclonal Antibody to Cryptococcus neoformans Glucuronoxylomannan Manifests
      Hydrolytic Activity for Both Peptides and Polysaccharides.
AB  - Studies in the 1980s first showed that some natural antibodies were "catalytic"
      and able to hydrolyze peptide or phosphodiester bonds in antigens. Many naturally
      occurring catalytic antibodies have since been isolated from human sera and
      associated with positive and negative outcomes in autoimmune disease and
      infection. The function and prevalence of these antibodies, however, remain
      unclear. A previous study suggested that the 18B7 monoclonal antibody against
      glucuronoxylomannan (GXM), the major component of the Cryptococcus neoformans
      polysaccharide capsule, hydrolyzed a peptide antigen mimetic. Using mass
      spectrometry and Forster resonance energy transfer techniques, we confirm and
      characterize the hydrolytic activity of 18B7 against peptide mimetics and show
      that 18B7 is able to hydrolyze an oligosaccharide substrate, providing the first
      example of a naturally occurring catalytic antibody for polysaccharides.
      Additionally, we show that the catalytic 18B7 antibody increases release of
      capsular polysaccharide from fungal cells. A serine protease inhibitor blocked
      peptide and oligosaccharide hydrolysis by 18B7, and a putative serine protease
      like active site was identified in the light chain variable region of the
      antibody. An algorithm was developed to detect similar sites present in unique
      antibody structures in the Protein Data Bank. The putative site was found in 14
      of 63 (22.2%) catalytic antibody structures and 119 of 1602 (7.4%) antibodies
      with no annotation of catalytic activity. The ability of many antibodies to
      cleave antigen, albeit slowly, supports the notion that this activity is an
      important immunoglobulin function in host defense. The discovery of GXM
      hydrolytic activity suggests new therapeutic possibilities for polysaccharide
      binding antibodies.

PMID- 27872189
TI  - Biophysical Evidence for Intrinsic Disorder in the C-terminal Tails of the
      Epidermal Growth Factor Receptor (EGFR) and HER3 Receptor Tyrosine Kinases.
AB  - The epidermal growth factor receptor (EGFR)/ErbB family of receptor tyrosine
      kinases includes oncogenes important in the progression of breast and other
      cancers, and they are targets for many drug development strategies. Each member
      of the ErbB family possesses a unique, structurally uncharacterized C-terminal
      tail that plays an important role in autophosphorylation and signal propagation.
      To determine whether these C-terminal tails are intrinsically disordered regions,
      we conducted a battery of biophysical experiments on the EGFR and HER3 tails.
      Using hydrogen/deuterium exchange mass spectrometry, we measured the
      conformational dynamics of intracellular half constructs and compared the tails
      with the ordered kinase domains. The C-terminal tails demonstrate more rapid
      deuterium exchange behavior when compared with the kinase domains. Next, we
      expressed and purified EGFR and HER3 tail-only constructs. Results from circular
      dichroism spectroscopy, size exclusion chromatography with multiangle light
      scattering, dynamic light scattering, analytical ultracentrifugation, and small
      angle X-ray scattering each provide evidence that the EGFR and HER3 C-terminal
      tails are intrinsically disordered with extended, non-globular structure in
      solution. The intrinsic disorder and extended conformation of these tails may be
      important for their function by increasing the capture radius and reducing the
      thermodynamic barriers for binding of downstream signaling proteins.

PMID- 27872190
TI  - Protein Phosphotyrosine Phosphatase 1B (PTP1B) in Calpain-dependent Feedback
      Regulation of Vascular Endothelial Growth Factor Receptor (VEGFR2) in Endothelial
      Cells: IMPLICATIONS IN VEGF-DEPENDENT ANGIOGENESIS AND DIABETIC WOUND HEALING.
AB  - The VEGF/VEGFR2/Akt/eNOS/NO pathway is essential to VEGF-induced angiogenesis. We
      have previously discovered a novel role of calpain in mediating VEGF-induced
      PI3K/AMPK/Akt/eNOS activation through Ezrin. Here, we sought to identify possible
      feedback regulation of VEGFR2 by calpain via its substrate protein
      phosphotyrosine phosphatase 1B (PTP1B), and the relevance of this pathway to VEGF
      induced angiogenesis, especially in diabetic wound healing. Overexpression of
      PTP1B inhibited VEGF-induced VEGFR2 and Akt phosphorylation in bovine aortic
      endothelial cells, while PTP1B siRNA increased both, implicating negative
      regulation of VEGFR2 by PTP1B. Calpain inhibitor ALLN induced VEGFR2 activation,
      which can be completely blocked by PTP1B overexpression. Calpain activation
      induced by overexpression or Ca/A23187 resulted in PTP1B cleavage, which can be
      blocked by ALLN. Moreover, calpain activation inhibited VEGF-induced VEGFR2
      phosphorylation, which can be restored by PTP1B siRNA. These data implicate
      calpain/PTP1B negative feedback regulation of VEGFR2, in addition to the primary
      signaling pathway of VEGF/VEGFR2/calpain/PI3K/AMPK/Akt/eNOS. We next examined a
      potential role of PTP1B in VEGF-induced angiogenesis. Endothelial cells
      transfected with PTP1B siRNA showed faster wound closure in response to VEGF.
      Aortic discs isolated from PTP1B siRNA-transfected mice also had augmented
      endothelial outgrowth. Importantly, PTP1B inhibition and/or calpain
      overexpression significantly accelerated wound healing in STZ-induced diabetic
      mice. In conclusion, our data for the first time demonstrate a
      calpain/PTP1B/VEGFR2 negative feedback loop in the regulation of VEGF-induced
      angiogenesis. Modulation of local PTP1B and/or calpain activities may prove
      beneficial in the treatment of impaired wound healing in diabetes.

PMID- 27872191
TI  - Structural and Biochemical Analyses Reveal the Mechanism of Glutathione S
      Transferase Pi 1 Inhibition by the Anti-cancer Compound Piperlongumine.
AB  - Glutathione S-transferase pi 1 (GSTP1) is frequently overexpressed in cancerous
      tumors and is a putative target of the plant compound piperlongumine (PL), which
      contains two reactive olefins and inhibits proliferation in cancer cells but not
      normal cells. PL exposure of cancer cells results in increased reactive oxygen
      species and decreased GSH. These data in tandem with other information led to the
      conclusion that PL inhibits GSTP1, which forms covalent bonds between GSH and
      various electrophilic compounds, through covalent adduct formation at the C7-C8
      olefin of PL, whereas the C2-C3 olefin of PL was postulated to react with GSH.
      However, direct evidence for this mechanism has been lacking. To investigate, we
      solved the X-ray crystal structure of GSTP1 bound to PL and GSH at 1.1 A
      resolution to rationalize previously reported structure activity relationship
      studies. Surprisingly, the structure showed that a hydrolysis product of PL (hPL)
      was conjugated to glutathione at the C7-C8 olefin, and this complex was bound to
      the active site of GSTP1; no covalent bond formation between hPL and GSTP1 was
      observed. Mass spectrometry (MS) analysis of the reactions between PL and GSTP1
      confirmed that PL does not label GSTP1. Moreover, MS data also indicated that
      nucleophilic attack on PL at the C2-C3 olefin led to PL hydrolysis. Although hPL
      inhibits GSTP1 enzymatic activity in vitro, treatment of cells susceptible to PL
      with hPL did not have significant anti-proliferative effects, suggesting that hPL
      is not membrane-permeable. Altogether, our data suggest a model wherein PL is a
      prodrug whose intracellular hydrolysis initiates the formation of the hPL-GSH
      conjugate, which blocks the active site of and inhibits GSTP1 and thereby cancer
      cell proliferation.

PMID- 27872194
TI  - Sample size and power for a stratified doubly randomized preference design.
AB  - The two-stage (or doubly) randomized preference trial design is an important tool
      for researchers seeking to disentangle the role of patient treatment preference
      on treatment response through estimation of selection and preference effects. Up
      until now, these designs have been limited by their assumption of equal
      preference rates and effect sizes across the entire study population. We propose
      a stratified two-stage randomized trial design that addresses this limitation. We
      begin by deriving stratified test statistics for the treatment, preference, and
      selection effects. Next, we develop a sample size formula for the number of
      patients required to detect each effect. The properties of the model and the
      efficiency of the design are established using a series of simulation studies. We
      demonstrate the applicability of the design using a study of Hepatitis C
      treatment modality, specialty clinic versus mobile medical clinic. In this
      example, a stratified preference design (stratified by alcohol/drug use) may more
      closely capture the true distribution of patient preferences and allow for a more
      efficient design than a design which ignores these differences (unstratified
      version).

PMID- 27872193
TI  - Critical Contribution of Nuclear Factor Erythroid 2-related Factor 2 (NRF2) to
      Electrophile-induced Interleukin-11 Production.
AB  - Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that
      plays a crucial role in protection of cells from electrophile-induced toxicity
      through up-regulating phase II detoxifying enzymes and phase III transporters. We
      previously reported that oxidative stress induces up-regulation of interleukin-11
      (IL-11), a member of the IL-6 family that ameliorates acetaminophen-induced liver
      toxicity. However, a role for IL-11 in protection of cells from electrophile
      induced toxicity remains unclear. Here we show that an environmental
      electrophile, 1,2-naphthoquinone (1,2-NQ), but not 15d-prostaglandin J2 (PGJ2) or
      tert-butylhydroxyquinone (tBHQ), induced IL-11 production. Consistent with a
      crucial role for prolonged ERK activation in H2O2-induced IL-11 production, 1,2
      NQ, but not 15d-PGJ2 or tBHQ, elicited prolonged ERK activation. Conversely,
      inhibition of the ERK pathway by a MEK inhibitor completely blocked 1,2-NQ
      induced IL-11 production at both protein and mRNA levels, further substantiating
      an intimate cross-talk between ERK activation and 1,2-NQ-induced IL-11
      production. Promoter analysis of the Il11 gene revealed that two AP-1 sites were
      essential for 1,2-NQ-induced promoter activities. Among various members of the AP
      1 family, Fra-1 was up-regulated by 1,2-NQ, and its up-regulation was blocked by
      a MEK inhibitor. Although NRF2 was not required for H2O2-induced IL11 up
      regulation, NRF2 was essential for 1,2-NQ-induced IL11 up-regulation by
      increasing Fra-1 proteins possibly through promoting mRNA translation of FOSL1
      Finally, intraperitoneal administration of 1,2-NQ induced body weight loss in
      wild-type mice, which was further exacerbated in Il11ra1-/- mice compared with
      Il11ra1+/- mice. Together, both Fra-1 and NRF2 play crucial roles in IL-11
      production that protects cells from 1,2-NQ intestinal toxicity.

PMID- 27872192
TI  - The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect
      Cell Motility in Src-transformed Human Epithelial Cells.
AB  - Tumor invasion into surrounding stromal tissue is a hallmark of high grade,
      metastatic cancers. Oncogenic transformation of human epithelial cells in culture
      can be triggered by activation of v-Src kinase, resulting in increased cell
      motility, invasiveness, and tumorigenicity and provides a valuable model for
      studying how changes in gene expression cause cancer phenotypes. Here, we show
      that epithelial cells transformed by activated Src show increased levels of DNA
      methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently
      blocks the increased cell motility and invasiveness induced by Src activation. A
      proteomic screen for chromatin regulators acting downstream of activated Src
      identified the replication-dependent histone chaperone CAF1 as an important
      factor for Src-mediated increased cell motility and invasion. We show that Src
      causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150
      (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed
      epithelial cells using siRNA was sufficient to recapitulate the increased
      motility and invasive phenotypes characteristic of transformed cells without
      activation of Src. Maintaining high levels of CAF1 by exogenous expression
      suppressed the increased cell motility and invasiveness phenotypes when Src was
      activated. These data identify a critical role of CAF1 in the dysregulation of
      cell invasion and motility phenotypes seen in transformed cells and also
      highlight an important role for epigenetic remodeling through DNA methylation for
      Src-mediated induction of cancer phenotypes.

PMID- 27872195
TI  - Estrogen Receptors and Signaling in Fibroids: Role in Pathobiology and
      Therapeutic Implications.
AB  - Uterine fibroids are the most common gynecologic tumors with a significant
      medical and financial burden. Several genetic, hormonal, and biological factors
      have been shown to contribute to the development and growth of fibroid tumors. Of
      these factors, estrogen is particularly critical since fibroids are considered
      estrogen dependent because no prepubertal cases have been described in the
      literature and tumors tend to regress after menopause. Understanding the role of
      estrogen in fibroids is not only important for understanding the pathobiology of
      fibroids but also for the development of successful therapeutics. In this review,
      we discuss the types and structure of estrogen receptors (nuclear and membrane
      bound, including alpha and beta receptors and G protein-coupled estrogen receptor
      1 GPER1). Estrogen-signaling pathways in fibroids include genomic (direct and
      indirect) and nongenomic including Ras-Raf-MEK (MAPK/Erk Kinase)-mitogen
      activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K)
      phosphatidylinositol-3,4,5-trisphosphate (PIP3)-Akt (Protein kinase B)-mammalian
      target of rapamycin (mTOR) pathways; shortly Ras-Raf-MEK-MAPK and PI3K-PIP3-Akt
      mTOR pathways. Several aberrations in estrogen receptors and signaling pathways
      are implicated in fibroid pathobiology. Current therapeutic and research agents
      targeting ERs/signaling include gonadotropin-releasing hormone (GnRH) agonists,
      GnRH antagonists, aromatase inhibitors, selective ER modulators, gene therapy,
      and others. Future research can identify potential targets for the development of
      novel treatments. In particular, epigenomics of estrogen activity and
      individualized (precision) medicine appear to be attractive areas for future
      research.

PMID- 27872196
TI  - Induction of Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 During the
      Periovulatory Period in the Rat Ovary.
AB  - Ectonucleotide pyrophosphatase/phosphodiesterase 3 ( Enpp3) is involved in
      multiple physiological processes, such as morphological changes and inflammatory
      processes. The present study investigated the spatiotemporal expression pattern
      and regulatory mechanisms controlling expression of Enpp3 in the rat ovary during
      the periovulatory period. Immature female rats were injected with pregnant mare
      serum gonadotropin to stimulate follicular development. Ovaries, granulosa cells,
      or theca-interstitial cells were collected at various times after human chorionic
      gonadotropin (hCG) administration. Real-time polymerase chain reaction analysis
      revealed that messenger RNA (mRNA) for Enpp3 was highly induced in both granulosa
      cells and theca-interstitial cells by hCG. In situ hybridization analysis
      demonstrated that Enpp3 mRNA expression was induced in theca cells at 4 hours
      after hCG, and the expression remained elevated until 12 hours after hCG. The
      expression of Enpp3 mRNA was stimulated in granulosa cells at 8 hours and reached
      the highest expression at 12 hours. Localization of Enpp3 mRNA was observed in
      newly forming corpora lutea by in situ hybridization. The hCG-stimulated
      expression of Enpp3 mRNA was blocked by a protein kinase C inhibitor (GF109203)
      instead of the protein kinase A inhibitor (H89). Furthermore, Enpp3 induction is
      dependent on new protein synthesis. Inhibition of progesterone action did not
      alter Enpp3 mRNA expression, whereas inhibition of prostaglandin synthesis or the
      epidermal growth factor pathway diminished Enpp3 mRNA levels. In conclusion, our
      findings suggest that the induction of the Enpp3 mRNA may be important for the
      morphological changes and inflammatory response during ovulation and
      luteinization.

PMID- 27872197
TI  - Plasma exosomes are enriched in Hsp70 and modulated by stress and cortisol in
      rainbow trout.
AB  - Exosomes are endosomally derived vesicles that are secreted from cells and
      contain a suite of molecules, including proteins and nucleic acids. Recent
      studies suggest the possibility that exosomes in circulation may be affecting
      recipient target cell function, but the modes of action are unclear. Here, we
      tested the hypothesis that exosomes are in circulation in fish plasma and that
      these vesicles are enriched with heat shock protein 70 (Hsp70). Exosomes were
      isolated from rainbow trout (Oncorhynchus mykiss) plasma using differential
      centrifugation, and their presence was confirmed by transmission electron
      microscopy and the exosomal marker acetylcholinesterase. Plasma exosomes were
      enriched with Hsp70, and this stress protein was transiently elevated in trout
      plasma in response to a heat shock in vivo Using trout hepatocytes in primary
      culture, we tested whether stress levels of cortisol, the principle
      corticosteroid in teleosts, regulates exosomal Hsp70 content. As expected, a 1-h
      heat shock (+15 degrees C above ambient) increased Hsp70 expression in
      hepatocytes, and this led to higher Hsp70 enrichment in exosomes over a 24-h
      period. However, cortisol treatment significantly reduced the expression of Hsp70
      in exosomes released from either unstressed or heat-shocked hepatocytes. This
      cortisol-mediated suppression was not specific to Hsp70 as beta-actin expression
      was also reduced in exosomes released from hepatocytes treated with the steroid.
      Our results suggest that circulating Hsp70 is released from target tissues via
      exosomes, and their release is modulated by stress and cortisol. Overall, we
      propose a novel role for extracellular vesicular transport of Hsp70 in the
      organismal stress response.

PMID- 27872200
TI  - Transferring scientific discovery to the public: The intramercurial planet Vulcan
      in 1860.

PMID- 27872198
TI  - In female rat heart mitochondria, oophorectomy results in loss of oxidative
      phosphorylation.
AB  - Oophorectomy in adult rats affected cardiac mitochondrial function. Progression
      of mitochondrial alterations was assessed at one, two and three months after
      surgery: at one month, very slight changes were observed, which increased at two
      and three months. Gradual effects included decrease in the rates of oxygen
      consumption and in respiratory uncoupling in the presence of complex I
      substrates, as well as compromised Ca2+ buffering ability. Malondialdehyde
      concentration increased, whereas the ROS-detoxifying enzyme Mn2+ superoxide
      dismutase (MnSOD) and aconitase lost activity. In the mitochondrial respiratory
      chain, the concentration and activity of complex I and complex IV decreased.
      Among other mitochondrial enzymes and transporters, adenine nucleotide carrier
      and glutaminase decreased. 2-Oxoglutarate dehydrogenase and pyruvate
      dehydrogenase also decreased. Data strongly suggest that in the female rat heart,
      estrogen depletion leads to progressive, severe mitochondrial dysfunction.

PMID- 27872199
TI  - Somatic individuality in context, a comparative case study.
AB  - Scholars have challenged the totalizing nature of the "geneticization thesis,"
      arguing that its brushstrokes are too broad to capture the complicated nature of
      the new genetics. One such challenge has come from Nikolas Rose's argument that
      genetic medicine is governed by a new biopolitics in which patients understand
      themselves as "somatic individuals" who treat their bodies as an "ethical
      substance" to be worked on in order to secure a healthier future. I argue that
      Rose's argument, while compelling, paints the new genetics in equally broad
      brushstrokes and that in order for a concept like somatic individuality to become
      useful, we must study its manifestation across different communities of at-risk
      individuals. I undertake such a study by analyzing discourse use in two online
      biosocial communities, showing how the decision-making situations specific to
      each affect representations of somatic individuality, often creating
      opportunities for the rhetorical repurposing of older discourses of genetic
      determinism.

PMID- 27872201
TI  - Identification of Chemical Compounds That Inhibit Protein Synthesis in
      Pseudomonas aeruginosa.
AB  - Four inhibitory compounds were identified using a poly-uridylic acid (polyU) mRNA
      directed aminoacylation/translation (A/T) protein synthesis system composed of
      phenylalanyl-tRNA synthetases (PheRS), ribosomes, and ribosomal factors from
      Pseudomonas aeruginosa in an in vitro screen of a synthetic compound library. The
      compounds were specific for inhibition of bacterial protein synthesis. In
      enzymatic assays, the compounds inhibited protein synthesis with IC50 values
      ranging from 20 to 60 MUM. Minimum inhibitory concentrations (MICs) were
      determined in cultures for a panel of pathogenic organisms, including
      Enterococcus faecalis, Escherichia coli, Haemophilus influenzae, P. aeruginosa,
      Staphylococcus aureus, and Streptococcus pneumoniae. All the compounds were
      observed to have broad-spectrum activity and inhibited an efflux pump mutant
      strain of P. aeruginosa with MICs of 0.5-16 MUg/mL. The molecular target of two
      compounds was determined to be PheRS. These two compounds were bacteriostatic
      against both Gram-positive and Gram-negative pathogens. In competition assays,
      they were not observed to compete with the natural substrates ATP or
      phenylalanine for active site binding. The other two compounds directly inhibited
      the ribosome and were bactericidal against both Gram-positive and Gram-negative
      pathogens. In cytotoxicity MTT testing in human cell lines, the compounds were
      shown to be from 2500- to 30,000-fold less active than the control staurosporine.

PMID- 27872202
TI  - Genome-Wide Overexpression Screen Identifies Genes Able to Bypass p16-Mediated
      Senescence in Melanoma.
AB  - Malignant melanomas often arise from nevi, which result from initial oncogene
      induced hyperproliferation of melanocytes that are maintained in a CDKN2A/p16
      mediated senescent state. Thus, genes that can bypass this senescence barrier are
      likely to contribute to melanoma development. We have performed a gain-of
      function screen of 17,030 lentivirally expressed human open reading frames (ORFs)
      in a melanoma cell line containing an inducible p16 construct to identify such
      genes. Genes known to bypass p16-induced senescence arrest, including the human
      papilloma virus 18 E7 gene ( HPV18E7), and genes such as the p16-binding CDK6
      with expected functions, as well as panel of novel genes, were identified,
      including high-mobility group box (HMGB) proteins. A number of these were further
      validated in two other models of p16-induced senescence. Tissue
      immunohistochemistry demonstrated higher levels of CDK6 in primary melanomas
      compared with normal skin and nevi. Reduction of CDK6 levels drove melanoma cells
      expressing functional p16 into senescence, demonstrating its contribution to
      bypass senescence.

PMID- 27872204
TI  - An injection of confidence: Scientists explore new and old methods to counter
      anti-vaccine propaganda and overcome vaccine hesitancy so as to increase
      vaccination rates.

PMID- 27872205
TI  - Molecular architecture of the yeast Elongator complex reveals an unexpected
      asymmetric subunit arrangement.
AB  - Elongator is a ~850 kDa protein complex involved in multiple processes from
      transcription to tRNA modification. Conserved from yeast to humans, Elongator is
      assembled from two copies of six unique subunits (Elp1 to Elp6). Despite the
      wealth of structural data on the individual subunits, the overall architecture
      and subunit organization of the full Elongator and the molecular mechanisms of
      how it exerts its multiple activities remain unclear. Using single-particle
      electron microscopy (EM), we revealed that yeast Elongator adopts a bilobal
      architecture and an unexpected asymmetric subunit arrangement resulting from the
      hexameric Elp456 subassembly anchored to one of the two Elp123 lobes that form
      the structural scaffold. By integrating the EM data with available subunit
      crystal structures and restraints generated from cross-linking coupled to mass
      spectrometry, we constructed a multiscale molecular model that showed the two
      Elp3, the main catalytic subunit, are located in two distinct environments. This
      work provides the first structural insights into Elongator and a framework to
      understand the molecular basis of its multifunctionality.

PMID- 27872203
TI  - Molecular mechanisms of asymmetric divisions in mammary stem cells.
AB  - Stem cells have the remarkable ability to undergo proliferative symmetric
      divisions and self-renewing asymmetric divisions. Balancing of the two modes of
      division sustains tissue morphogenesis and homeostasis. Asymmetric divisions of
      Drosophila neuroblasts (NBs) and sensory organ precursor (SOP) cells served as
      prototypes to learn what we consider now principles of asymmetric mitoses. They
      also provide initial evidence supporting the notion that aberrant symmetric
      divisions of stem cells could correlate with malignancy. However, transferring
      the molecular knowledge of circuits underlying asymmetry from flies to mammals
      has proven more challenging than expected. Several experimental approaches have
      been used to define asymmetry in mammalian systems, based on daughter cell fate,
      unequal partitioning of determinants and niche contacts, or proliferative
      potential. In this review, we aim to provide a critical evaluation of the assays
      used to establish the stem cell mode of division, with a particular focus on the
      mammary gland system. In this context, we will discuss the genetic alterations
      that impinge on the modality of stem cell division and their role in breast
      cancer development.

PMID- 27872209
TI  - Depletion of Neural Crest-Derived Cells Leads to Reduction in Plasma
      Noradrenaline and Alters B Lymphopoiesis.
AB  - Hematopoietic stem cells and their lymphoid progenitors are supported by the bone
      marrow (BM) microenvironmental niches composed of various stromal cells and
      Schwann cells and sympathetic nerve fibers. Although neural crest (NC) cells
      contribute to the development of all the three, their function in BM is not well
      understood. In this study, NC-derived cells were ablated with diphtheria toxin in
      double-transgenic mice expressing NC-specific Cre and Cre-driven diphtheria toxin
      receptor with yellow fluorescent protein reporter. We found that yellow
      fluorescent protein-expressing, NC-derived nonhematopoietic cells in BM expressed
      hematopoietic factors Cxcl12 and stem cell factor The ablation of NC-derived
      cells led to a significant decrease in B cell progenitors but not in
      hematopoietic stem cells or myeloid lineage cells in BM. Interestingly, plasma
      noradrenaline was markedly decreased in these mice. The i.p. administration of 6
      hydroxydopamine, a known neurotoxin for noradrenergic neurons, led to a similar
      phenotype, whereas the administration of a noradrenaline precursor in NC-ablated
      mice partially rescued this phenotype. Additionally, the continuous
      administration of adrenergic receptor beta antagonists partially decreased the
      number of B cell progenitors while preserving B lymphopoiesis in vitro. Taken
      together, our results indicate that NC-derived cell depletion leads to abnormal B
      lymphopoiesis partially through decreased plasma noradrenaline, suggesting this
      as a novel mechanism regulated by molecules released by the sympathetic neurons.

PMID- 27872208
TI  - Blocking Virus Replication during Acute Murine Cytomegalovirus Infection
      Paradoxically Prolongs Antigen Presentation and Increases the CD8+ T Cell
      Response by Preventing Type I IFN-Dependent Depletion of Dendritic Cells.
AB  - Increasing amounts of pathogen replication usually lead to a proportionate
      increase in size and effector differentiation of the CD8+ T cell response, which
      is attributed to increased Ag and inflammation. Using a murine CMV that is highly
      sensitive to the antiviral drug famciclovir to modulate virus replication, we
      found that increased virus replication drove increased effector CD8+ T cell
      differentiation, as expected. Paradoxically, however, increased virus replication
      dramatically decreased the size of the CD8+ T cell response to two immunodominant
      epitopes. The decreased response was due to type I IFN-dependent depletion of
      conventional dendritic cells and could be reproduced by specific depletion of
      dendritic cells from day 2 postinfection or by sterile induction of type I IFN.
      Increased virus replication and type I IFN specifically inhibited the response to
      two immunodominant epitopes that are known to be dependent on Ag cross-presented
      by DCs, but they did not inhibit the response to "inflationary" epitopes whose
      responses can be sustained by infected nonhematopoietic cells. Our results show
      that type I IFN can suppress CD8+ T cell responses to cross-presented Ag by
      depleting cross-presenting conventional dendritic cells.

PMID- 27872207
TI  - Myeloid-Specific Gene Deletion of Protein Phosphatase 2A Magnifies MyD88- and
      TRIF-Dependent Inflammation following Endotoxin Challenge.
AB  - Protein phosphatase 2A (PP2A) is a member of the intracellular serine/threonine
      phosphatases. Innate immune cell activation triggered by pathogen-associated
      molecular patterns is mediated by various protein kinases, and PP2A plays a
      counter-regulatory role by deactivating these kinases. In this study, we
      generated a conditional knockout of the alpha isoform of the catalytic subunit of
      PP2A (PP2ACalpha). After crossing with myeloid-specific cre-expressing mice,
      effective gene knockout was achieved in various myeloid cells. The myeloid
      specific knockout mice (lyM-PP2Afl/fl) showed higher mortality in response to
      endotoxin challenge and bacterial infection. Upon LPS challenge, serum levels of
      TNF-alpha, KC, IL-6, and IL-10 were significantly increased in lyM-PP2Afl/fl
      mice, and increased phosphorylation was observed in MAPK pathways (p38, ERK, JNK)
      and the NF-kappaB pathway (IKKalpha/beta, NF-kappaB p65) in bone marrow-derived
      macrophages (BMDMs) from knockout mice. Heightened NF-kappaB activation was not
      associated with degradation of IkappaBalpha; instead, enhanced phosphorylation of
      the NF-kappaB p65 subunit and p38 phosphorylation-mediated TNF-alpha mRNA
      stabilization appear to contribute to the increased TNF-alpha expression. In
      addition, increased IL-10 expression appears to be due to PP2ACalpha-knockout
      induced IKKalpha/beta hyperactivation. Microarray experiments indicated that the
      Toll/IL-1R domain-containing adaptor inducing IFN-beta/ TNFR-associated factor 3
      pathway was highly upregulated in LPS-treated PP2ACalpha-knockout BMDMs, and
      knockout BMDMs had elevated IFN-alpha/beta production compared with control
      BMDMs. Serum IFN-beta levels from PP2ACalpha-knockout mice treated with LPS were
      also greater than those in controls. Thus, we demonstrate that PP2A plays an
      important role in regulating inflammation and survival in the setting of septic
      insult by targeting MyD88- and Toll/IL-1R domain-containing adaptor inducing IFN
      beta-dependent pathways.

PMID- 27872210
TI  - Distribution and Activation of CD8+ T Cells in the Duodenal Mucosa before and
      after HIV Seroconversion.
AB  - CD8+ T cells in the intestinal mucosa influence the HIV-associated pathogenesis,
      but little is known about the dynamics of mucosal CD8+ T cell counts and
      activation of these cells during the course of infection. In this study, mucosal
      CD8+ T cells in the duodenum were studied at different stages of HIV infection,
      starting from the seronegative phase. In seronegative acute HIV infection, CD8+ T
      cell counts increased in the epithelium, but not in the lamina propria.
      Infiltration of the lamina propria by peripherally expanded CD8+ T cells was
      observed after seroconversion. Highest increase in the expression of perforin,
      the rate-limiting molecule for cytotoxic CD8+ T cell activity, was evident in the
      lamina propria of seronegative acutely HIV-infected patients. The number of
      perforin-expressing cells in the lamina propria of acutely HIV-infected patients
      was positively associated with biomarkers of enterocyte damage and microbial
      translocation. After seroconversion, perforin expression was downregulated in the
      lamina propria, but not in the epithelium. In conclusion, our findings
      demonstrate that intraepithelial and lamina propria CD8+ T cells exhibit
      different dynamics of numerical alteration and cytotoxic activity in HIV-infected
      patients. Moreover, our results suggest that perforin-dependent cytotoxic
      mechanisms by CD8+ T cells could impair the intestinal mucosal barrier already in
      the seronegative phase of acute HIV infection, thereby inducing microbial
      translocation as one of the earliest pathological events in HIV infection.

PMID- 27872211
TI  - Accurate Structure Prediction of CDR H3 Loops Enabled by a Novel Structure-Based
      C-Terminal Constraint.
AB  - Ab structure prediction has made great strides, but accurately modeling CDR H3
      loops remains elusive. Unlike the other five CDR loops, CDR H3 does not adopt
      canonical conformations and must be modeled de novo. During Antibody Modeling
      Assessment II, we found that biasing simulations toward kinked conformations
      enables generating low-root mean square deviation models (Weitzner et al. 2014.
      Proteins 82: 1611-1623), and since then, we have presented new geometric
      parameters defining the kink conformation (Weitzner et al. 2015. Structure 23:
      302-311). In this study, we use these parameters to develop a new biasing
      constraint. When applied to a benchmark set of high-quality CDR H3 loops, the
      average minimum root mean square deviation sampled is 0.93 A, compared with 1.34
      A without the constraint. We then test the performance of the constrained de novo
      method for homology modeling and rigid-body docking and present the results for
      1) the Antibody Modeling Assessment II targets, 2) the 2009 RosettaAntibody
      benchmark set, and 3) the high-quality set.

PMID- 27872212
TI  - A Proinflammatory Role of Type 2 Innate Lymphoid Cells in Murine Immune-Mediated
      Hepatitis.
AB  - Type 2 innate lymphoid cells (ILC2) mediate inflammatory immune responses in the
      context of diseases triggered by the alarmin IL-33. In recent years, IL-33 has
      been implicated in the pathogenesis of immune-mediated liver diseases. However,
      the immunoregulatory function of ILC2s in the inflamed liver remains elusive.
      Using the murine model of Con A-induced immune-mediated hepatitis, we showed that
      selective expansion of ILC2s in the liver was associated with highly elevated
      hepatic IL-33 expression, severe liver inflammation, and infiltration of
      eosinophils. CD4+ T cell-mediated tissue damage and subsequent IL-33 release were
      responsible for the activation of hepatic ILC2s that produced the type 2
      cytokines IL-5 and IL-13 during liver inflammation. Interestingly, ILC2 depletion
      correlated with less severe hepatitis and reduced accumulation of eosinophils in
      the liver, whereas adoptive transfer of hepatic ILC2s aggravated liver
      inflammation and tissue damage. We further showed that, despite expansion of
      hepatic ILC2s, 3-d IL-33 treatment before Con A challenge potently suppressed
      development of immune-mediated hepatitis. We found that IL-33 not only activated
      hepatic ILC2s but also expanded CD4+ Foxp3+ regulatory T cells (Treg) expressing
      the IL-33 receptor ST2 in the liver. This Treg subset also accumulated in the
      liver during resolution of immune-mediated hepatitis. In summary, hepatic ILC2s
      are poised to respond to the release of IL-33 upon liver tissue damage through
      expression of type 2 cytokines thereby participating in the pathogenesis of
      immune-mediated hepatitis. Inflammatory activity of ILC2s might be regulated by
      IL-33-elicited ST2+ Tregs that also arise in immune-mediated hepatitis.

PMID- 27872214
TI  - Effects of prolonged anoxia on electrical activity of the heart in crucian carp
      (Carassius carassius).
AB  - The effects of sustained anoxia on cardiac electrical excitability were examined
      in the anoxia-tolerant crucian carp (Carassius carassius). The electrocardiogram
      (ECG) and expression of excitation-contraction coupling genes were studied in
      fish acclimatised to normoxia in summer (+18 degrees C) or winter (+2 degrees C),
      and in winter fish after 1, 3 and 6 weeks of anoxia. Anoxia induced a sustained
      bradycardia from a heart rate of 10.3+/-0.77 beats min-1 to 4.1+/-0.29 beats min
      1 (P<0.05) after 5 weeks, and heart rate slowly recovered to control levels when
      oxygen was restored. Heart rate variability greatly increased under anoxia, and
      completely recovered under re-oxygenation. The RT interval increased from 2.8+/
      0.34 s in normoxia to 5.8+/-0.44 s under anoxia (P<0.05), which reflects a
      doubling of the ventricular action potential (AP) duration. Acclimatisation to
      winter induced extensive changes in gene expression relative to summer
      acclimatised fish, including depression in those genes coding for the
      sarcoplasmic reticulum calcium pump (Serca2a_q2) and ATP-sensitive K+ channels
      (Kir6.2) (P<0.05). Genes of delayed rectifier K+ (kcnh6) and Ca2+ channels
      (cacna1c) were up-regulated in winter fish (P<0.05). In contrast, the additional
      challenge of anoxia caused only minor changes in gene expression, e.g. depressed
      expression of Kir2.2b K+ channel gene (kcnj12b), whereas expression of Ca2+
      (cacna1a, cacna1c and cacna1g) and Na+ channel genes (scn4a and scn5a) was not
      affected. These data suggest that low temperature pre-conditions the crucian carp
      heart for winter anoxia, whereas sustained anoxic bradycardia and prolongation of
      AP duration are directly induced by oxygen shortage without major changes in gene
      expression.

PMID- 27872215
TI  - Intramolecular interactions that control voltage sensitivity in the jShak1
      potassium channel from Polyorchis penicillatus.
AB  - Voltage-gated potassium ion (Kv) channel proteins respond to changes in membrane
      potential by changing the probability of K+ flux through an ion-selective pore.
      Kv channels from different paralogous and orthologous families have widely
      varying V50 values. The voltage-sensing transmembrane helices (S4) of different
      channels contain four to seven basic residues that are responsible for
      transducing changes in transmembrane potential into the energy required to shift
      the equilibrium between the open- and closed-channel conformations. These
      residues also form electrostatic interaction networks with acidic residues in the
      S2 and S3 helices that stabilize the open and the closed states to different
      extents. The length and composition of the extracellular loop connecting the S3
      and S4 helices (S3-S4 loop) also shape the voltage response. We describe
      mutagenesis experiments on the jellyfish (Polyorchis penicillatus) Kv1 family
      jShak1 channel to evaluate how variants of the S3-S4 loop affect the voltage
      sensitivity of this channel. In combination with changes in the length and
      composition of the S3-S4 linker, we mutated a residue on the S2 helix (N227) that
      in most Kv1 family channels is glutamate (E226 in mouse Kv1.2, E283 in D.
      melanogaster Shaker). Some individual loop replacement mutants cause major
      changes in voltage sensitivity, depending on a combination of length and
      composition. Pairwise combinations of the loop mutations and the S2 mutations
      interact to yield quantitatively distinct, non-additive changes in voltage
      sensitivity. We conclude that the S3-S4 loop interacts energetically with the
      residue at position N227 during the transitions between open and closed states of
      the channel.

PMID- 27872216
TI  - The effect of temperature adaptation on the ubiquitin-proteasome pathway in
      notothenioid fishes.
AB  - There is an accumulating body of evidence suggesting that the sub-zero Antarctic
      marine environment places physiological constraints on protein homeostasis.
      Levels of ubiquitin (Ub)-conjugated proteins, 20S proteasome activity and mRNA
      expression of many proteins involved in both the Ub tagging of damaged proteins
      as well as the different complexes of the 26S proteasome were measured to examine
      whether there is thermal compensation of the Ub-proteasome pathway in Antarctic
      fishes to better understand the efficiency of the protein degradation machinery
      in polar species. Both Antarctic (Trematomus bernacchii, Pagothenia
      borchgrevinki) and non-Antarctic (Notothenia angustata, Bovichtus variegatus)
      notothenioids were included in this study to investigate the mechanisms of cold
      adaptation of this pathway in polar species. Overall, there were significant
      differences in the levels of Ub-conjugated proteins between the Antarctic
      notothenioids and B. variegatus, with N. angustata possessing levels very similar
      to those of the Antarctic fishes. Proteasome activity in the gills of Antarctic
      fishes demonstrated a high degree of temperature compensation such that activity
      levels were similar to activities measured in their temperate relatives at
      ecologically relevant temperatures. A similar level of thermal compensation of
      proteasome activity was not present in the liver of two Antarctic fishes. Higher
      gill proteasome activity is likely due in part to higher cellular levels of
      proteins involved in the Ub-proteasome pathway, as evidenced by high mRNA
      expression of relevant genes. Reduced activity of the Ub-proteasome pathway does
      not appear to be the mechanism responsible for elevated levels of denatured
      proteins in Antarctic fishes, at least in the gills.

PMID- 27872217
TI  - An Analysis of Human Dorsal Hand Skin Texture Using Hyperspectral Imaging
      Technique for Assessing the Skin Aging Process.
AB  - Skin texture has become an important issue in recent research with applications
      in the cosmetic industry and medicine. In this paper, we analyzed the dependence
      of skin texture features on wavelength as well as on different parameters (age
      and gender) of human participants using grey-level co-occurrence matrix and
      hyperspectral imaging technique for a more accurate quantitative assessment of
      the aging process. A total of 42 healthy participants (men and women; age range,
      20-70 years) was enrolled in this study. A region of interest was selected from
      the hyperspectral images. The results were analyzed in terms of texture using the
      gray-level co-occurrence matrix which generated four features (homogeneity,
      contrast, entropy, and correlation). The results showed that most of these
      features displayed variations with wavelength (the exception was entropy), with
      higher variations in women. Only correlation in both sexes and contrast in men
      proved to vary statistically significant with age, making them the targeted
      variables in future attempts to characterize aging skin using the complex method
      of hyperspectral imaging. In conclusion, by using hyperspectral imaging some
      measure of the degree of damage or the aging process of the hand skin can be
      obtained, mainly in terms of correlation values. At the present time, reasonable
      explanations that can link the process of skin aging and the above mentioned
      features could not be found, but deeper investigations are on the way.

PMID- 27872213
TI  - Autocrine Type I IFN Signaling in Dendritic Cells Stimulated with Fungal beta
      Glucans or Lipopolysaccharide Promotes CD8 T Cell Activation.
AB  - Type I IFNs are key mediators of immune defense against viruses and bacteria.
      Type I IFNs were also previously implicated in protection against fungal
      infection, but their roles in antifungal immunity have not been thoroughly
      investigated. A recent study demonstrated that bacterial and fungal beta-glucans
      stimulate IFN-beta production by dendritic cells (DCs) following detection by the
      Dectin-1 receptor, but the effects of beta-glucan-induced type I IFNs have not
      been defined. We investigated whether type I IFNs regulate CD8 T cell activation
      by fungal beta-glucan particle-stimulated DCs. We demonstrate that beta-glucan
      stimulated DCs induce CD8 T cell proliferation, activation marker (CD44 and CD69)
      expression, and production of IFN-gamma, IL-2, and granzyme B. Moreover, we show
      that type I IFNs support robust CD8 T cell activation (proliferation and IFN
      gamma and granzyme B production) by beta-glucan-stimulated DCs in vitro and in
      vivo due to autocrine effects on the DCs. Specifically, type I IFNs promote Ag
      presentation on MHC I molecules, CD86 and CD40 expression, and the production of
      IL-12 p70, IL-2, IL-6, and TNF-alpha by beta-glucan-stimulated DCs. We also
      demonstrate a role for autocrine type I IFN signaling in bacterial LPS-induced DC
      maturation, although, in the context of LPS stimulation, this mechanism is not so
      critical for CD8 T cell activation (promotes IFN-gamma production but not
      proliferation or granzyme B production). This study provides insight into the
      mechanisms underlying CD8 T cell activation during infection, which may be useful
      in the rational design of vaccines directed against pathogens and tumors.

PMID- 27872218
TI  - Wavelength Scanning with a Tilting Interference Filter for Glow-Discharge
      Elemental Imaging.
AB  - Glow discharges have long been used for depth profiling and bulk analysis of
      solid samples. In addition, over the past decade, several methods of obtaining
      lateral surface elemental distributions have been introduced, each with its own
      strengths and weaknesses. Challenges for each of these techniques are acceptable
      optical throughput and added instrumental complexity. Here, these problems are
      addressed with a tilting-filter instrument. A pulsed glow discharge is coupled to
      an optical system comprising an adjustable-angle tilting filter, collimating and
      imaging lenses, and a gated, intensified charge-coupled device (CCD) camera,
      which together provide surface elemental mapping of solid samples. The tilting
      filter spectrometer is instrumentally simpler, produces less image distortion,
      and achieves higher optical throughput than a monochromator-based instrument, but
      has a much more limited tunable spectral range and poorer spectral resolution. As
      a result, the tilting-filter spectrometer is limited to single-element or two
      element determinations, and only when the target spectral lines fall within an
      appropriate spectral range and can be spectrally discerned. Spectral
      interferences that result from heterogeneous impurities can be flagged and
      overcome by observing the spatially resolved signal response across the available
      tunable spectral range. The instrument has been characterized and evaluated for
      the spatially resolved analysis of glow-discharge emission from selected but
      representative samples.

PMID- 27872219
TI  - Shortwave Infrared Imaging Spectroscopy for Analysis of Ancient Paintings.
AB  - Spectral analysis is one of the main non-destructive techniques used to examine
      cultural relics. Hyperspectral imaging technology, especially on the shortwave
      infrared (SWIR) band, can clearly extract information from paintings, such as
      color, pigment composition, damage characteristics, and painting techniques. All
      of these characteristics have significant scientific and practical value in the
      study of ancient paintings and other relics and in their protection and
      restoration. In this study, an ancient painting, numbered Gu-6541, which had been
      found in the Forbidden City, served as a sample. A ground-based SWIR imaging
      spectrometer was used to produce hyperspectral images with high spatial and
      spectral resolution. Results indicated that SWIR imaging spectral data greatly
      facilitates the extraction of line features used in drafting, even using a single
      band image. It can be used to identify and classify mineral pigments used in
      paintings. These images can detect alterations and traces of daub used in
      painting corrections and, combined with hyperspectral data analysis methods such
      as band combination or principal component analysis, such information can be
      extracted to highlight outcomes of interest. In brief, the SWIR imaging spectral
      technique was found to have a highly favorable effect on the extraction of line
      features from drawings and on the identification of colors, classification of
      paintings, and extraction of hidden information.

PMID- 27872223
TI  - Atypical meningioma mimicking high-grade glioma.

PMID- 27872224
TI  - Two different phenomena in basic motor speech performance in premanifest
      Huntington disease.

PMID- 27872222
TI  - Three-dimensional modeling of Eagle syndrome.

PMID- 27872225
TI  - The head trauma amnesia cure: The making of a medical myth.

PMID- 27872226
TI  - Pediatric multiple sclerosis: The 2015 Sydney Carter Award Lecture.

PMID- 27872227
TI  - On Your Mother's Passing; Psychosis, Self-Portrait With.

PMID- 27872228
TI  - Child Neurology: Diencephalic syndrome-like presentation of a cervicomedullary
      brainstem tumor.
AB  - Diencephalic syndrome is a rare clinical entity, traditionally encompassing
      severe failure to thrive, nystagmus, and hyperkinesis, secondary to an
      intracranial neoplasm that is classically located in the hypothalamic region and
      its vicinity. However, the presenting features can be variable, often resulting
      in delayed diagnosis, which may worsen prognosis. This case report describes the
      atypical presentation of a posterior fossa tumor with features reminiscent of
      diencephalic syndrome that have not previously been reported in the literature.
      We report a 21-month-old girl with a cervicomedullary brainstem astrocytoma, who
      presented with isolated gross motor developmental delay, decreased growth
      velocity, and stridor. The neurologic signs frequently reported in patients with
      diencephalic syndrome were absent; however, severe failure to thrive was present.
      This case broadens the etiologic differential diagnosis of diencephalic syndrome
      in addition to the traditional hypothalamic region tumor location. This case
      urges physicians to consider central neurologic processes in the differential
      diagnosis of children with refractory failure to thrive with or without classical
      features of diencephalic syndrome, in whom etiology is not identified by routine
      investigations, given its importance in determining prognosis and management.

PMID- 27872229
TI  - Clinical Reasoning: A 64-year-old man with visual distortions.

PMID- 27872230
TI  - Journal Club: Depression before and after diagnosis with amyotrophic lateral
      sclerosis.

PMID- 27872231
TI  - Teaching NeuroImages: Giant neurocysticercosis with unusual imaging
      manifestations.

PMID- 27872232
TI  - Therapeutic Potential of Progranulin in Hyperhomocysteinemia-Induced Cardiorenal
      Dysfunction.
AB  - Hyperhomocysteinemia (hHcys) is an important independent risk factor for the
      development of cardiovascular disease and end-stage renal disease. Although
      multiple approaches lowering the levels of homocysteine have been used in
      experimental studies and clinical trials, there is no effective therapy available
      to fully prevent homocysteine-induced injury. Therefore, identifying key
      molecules in the pathogenic pathways may provide clues to develop new therapeutic
      strategies for the treatment of hHcys-associated injury beyond lowering the
      plasma homocysteine levels. In this study, we found that the levels of
      progranulin (PGRN), an autocrine growth factor, were significantly reduced in the
      kidney and heart from a mouse model of hHcys. We further observed that in hHcys,
      PGRN-deficient mice significantly exacerbated cardiorenal injury as evidenced by
      higher levels of urinary albumin excretion, more severe renal morphological
      injuries, including pronounced glomerular basement membrane thickening and
      podocyte foot process effacement, and adverse myocardial remodeling versus wild
      type mice. Mechanistically, we found that PGRN-medicated Wnt/beta-catenin
      signaling was one of the critical signal transduction pathways that links
      homocysteine to cardiorenal injury. Importantly, we finally provided direct
      evidence for the therapeutic potential of PGRN in mice with hHcys by pretreatment
      with recombinant human PGRN. Collectively, our results suggest that PGRN may be
      an innovative therapeutic strategy for treating patients with hHcys.

PMID- 27872234
TI  - Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4
      Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired
      Endothelium-Dependent Hyperpolarization in Hypertension.
AB  - Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in
      hypertension, but the underlying mechanisms have not yet been determined. The
      activation of small- and intermediate-conductance of Ca2+-activated K+ channels
      (SKCa and IKCa) underpins EDH-mediated responses. It was recently reported that
      Ca2+ influx through endothelial transient receptor potential vanilloid type 4
      channel (TRPV4) is a prerequisite for the activation of SKCa/IKCa in endothelial
      cells in specific beds. Here, we attempted to determine whether the impairment of
      EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IKCa, using
      isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously
      hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY
      arteries, EDH-mediated responses were reduced by a combination of SKCa/IKCa
      blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and
      by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In
      the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were
      significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4
      activator, evoked robust hyperpolarization and relaxation in WKY arteries. In
      contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small
      and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5
      dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SKCa
      activator, were marginally decreased in SHRSP arteries compared with WKY
      arteries. The expression of endothelial TRPV4 and SKCa protein was significantly
      decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas
      function and expression of IKCa were preserved in SHRSP arteries. These findings
      suggest that EDH-mediated responses are impaired in superior mesenteric arteries
      of SHRSP because of a reduction in both TRPV4 and SKCa input to EDH.

PMID- 27872233
TI  - Effects of Percutaneous Transluminal Renal Angioplasty on Office and Home Blood
      Pressure and Home Blood Pressure Variability in Hypertensive Patients With Renal
      Artery Stenosis.
AB  - This study included 126 hypertensive patients with renal artery stenosis (mean
      age, 63 years; 22.2% fibromuscular dysplasia [FMD]) and investigated the effects
      of percutaneous transluminal renal angioplasty on office and home blood pressure
      (BP), and BP variability estimates derived from home BP, both at baseline and up
      to 12 months after angioplasty. Home BP was measured for 7 consecutive days, and
      the threshold defining uncontrolled home BP was >=135/85 mm Hg. In both the FMD
      and atherosclerotic stenosis (ARAS) groups, office and home BP decreased
      significantly after angioplasty (all P<0.01), but the decrease in morning home (
      22+/-19 versus -10+/-20 mm Hg; P<0.01) but not in office (-32+/-24 versus -23+/
      28 mm Hg; P=0.11) systolic BP at 12 months was significantly greater in FMD. In
      both groups, all morning BP variability indices except the coefficient of
      variation in ARAS decreased significantly after revascularization (all P<0.05 by
      repeated-measures ANOVA). The decrease in all morning systolic BP variability
      estimates was greater for FMD than for ARAS (all P<0.05 by 2-way repeated
      measures ANOVA), with the exception of variability independent of the mean
      (P=0.11). The prevalence of uncontrolled home BP was 77.0% at baseline and 38.9%
      after revascularization. Duration of hypertension (odds ratio, 1.48), ARAS (odds
      ratio, 3.18), and the presence of proteinuria (odds ratio, 2.10) were independent
      predictors of uncontrolled home BP after revascularization (all P<0.05). In
      conclusion, renal angioplasty produced a greater decrease of morning home
      systolic BP in FMD; however, in both groups, it decreased BP variability
      irrespective of BP response. Measurement of home BP seems to be important for
      treatment success, especially in ARAS.

PMID- 27872235
TI  - Specific Aldosterone Synthase Inhibition: A Potential Improvement Over
      Mineralocorticoid Receptor Antagonism?

PMID- 27872236
TI  - Preclinical and Early Clinical Profile of a Highly Selective and Potent Oral
      Inhibitor of Aldosterone Synthase (CYP11B2).
AB  - : Primary hyperaldosteronism is a common cause of resistant hypertension.
      Aldosterone is produced in the adrenal by aldosterone synthase (AS, encoded by
      the gene CYP11B2). AS shares 93% homology to 11beta-hydroxylase (encoded by the
      gene CYP11B1), responsible for cortisol production. This homology has hitherto
      impeded the development of a drug, which selectively suppresses aldosterone but
      not cortisol production, as a new treatment for primary hyperaldosteronism. We
      now report the development of RO6836191 as a potent (Ki 13 nmol/L) competitive
      inhibitor of AS, with in vitro selectivity >100-fold over 11beta-hydroxylase. In
      cynomolgus monkeys challenged with synthetic adrenocorticotropic hormone, single
      doses of RO6836191 inhibited aldosterone synthesis without affecting the
      adrenocorticotropic hormone-induced rise in cortisol. In repeat-dose toxicity
      studies in monkeys, RO6836191 reproduced the adrenal changes of the AS-/- mouse:
      expansion of the zona glomerulosa; increased expression of AS (or disrupted green
      fluorescent protein gene in the AS-/- mouse); hypertrophy, proliferation, and
      apoptosis of zona glomerulosa cells. These changes in the monkey were partially
      reversible and partially preventable by electrolyte supplementation and treatment
      with an angiotensin-converting enzyme inhibitor. In healthy subjects, single
      doses of RO6836191, across a 360-fold dose range, reduced plasma and urine
      aldosterone levels with maximum suppression at a dose of 10 mg, but unchanged
      cortisol, on adrenocorticotropic hormone challenge, up to 360 mg, and increase in
      the precursors 11-deoxycorticosterone and 11-deoxycortisol only at or >90 mg. In
      conclusion, RO6836191 demonstrates that it is possible to suppress aldosterone
      production completely in humans without affecting cortisol production. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01995383.

PMID- 27872238
TI  - Phagosomal Neutralization by the Fungal Pathogen Candida albicans Induces
      Macrophage Pyroptosis.
AB  - The interaction of Candida albicans with the innate immune system is the key
      determinant of the pathogen/commensal balance and has selected for adaptations
      that facilitate the utilization of nutrients commonly found within the host,
      including proteins and amino acids; many of the catabolic pathways needed to
      assimilate these compounds are required for persistence in the host. We have
      shown that C. albicans co-opts amino acid catabolism to generate and excrete
      ammonia, which raises the extracellular pH, both in vitro and in vivo and induces
      hyphal morphogenesis. Mutants defective in the uptake or utilization of amino
      acids, such as those lacking STP2, a transcription factor that regulates the
      expression of amino acid permeases, are impaired in multiple aspects of fungus
      macrophage interactions resulting from an inability to neutralize the phagosome.
      Here we identified a novel role in amino acid utilization for Ahr1p, a
      transcription factor previously implicated in regulation of adherence and hyphal
      morphogenesis. Mutants lacking AHR1 were defective in growth, alkalinization, and
      ammonia release on amino acid-rich media, similar to stp2Delta and ahr1Delta
      stp2Delta cells, and occupied more acidic phagosomes. Notably, ahr1Delta and
      stp2Delta strains did not induce pyroptosis, as measured by caspase-1-dependent
      interleukin-1beta release, though this phenotype could be suppressed by
      pharmacological neutralization of the phagosome. Altogether, we show that C.
      albicans-driven neutralization of the phagosome promotes hyphal morphogenesis,
      sufficient for induction of caspase-1-mediated macrophage lysis.

PMID- 27872237
TI  - Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis
      Infection Does Not Require Interleukin-22.
AB  - Signaling through Toll-like receptors (TLRs), the main receptors in innate
      immunity, is essential for the defense of mucosal surfaces. It was previously
      shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate,
      transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or
      viral infections of the mucosa. This process was dependent on the activation of
      type 3 innate lymphoid cells (ILCs). The objective of the present study was to
      analyze the effects of flagellin treatment in a murine model of oral infection
      with Yersinia pseudotuberculosis (an invasive, Gram-negative, enteropathogenic
      bacterium that targets the small intestine). We found that systemic
      administration of flagellin significantly increased the survival rate after
      intestinal infection (but not systemic infection) by Y. pseudotuberculosis This
      protection was associated with a low bacterial count in the gut and the spleen.
      In contrast, no protection was afforded by administration of the TLR4 agonist
      lipopolysaccharide, suggesting the presence of a flagellin-specific effect.
      Lastly, we found that TLR5- and MyD88-mediated signaling was required for the
      protective effects of flagellin, whereas neither lymphoid cells nor IL-22 was
      involved.

PMID- 27872239
TI  - Experimental Infection of Pig-Tailed Macaques (Macaca nemestrina) with Mycoplasma
      genitalium.
AB  - Mycoplasma genitalium is an underappreciated cause of human reproductive tract
      disease, characterized by persistent, often asymptomatic, infection. Building on
      our previous experiments using a single female pig-tailed macaque as a model for
      M. genitalium infection (G. E. Wood, S. L. Iverson-Cabral, D. L. Patton, P. K.
      Cummings, Y. T. Cosgrove Sweeney, and P. A. Totten, Infect Immun 81:2938-2951,
      2013, https://doi.org/10.1128/IAI.01322-12), we cervically inoculated eight
      additional animals, two of which were simultaneously inoculated in salpingeal
      tissue autotransplanted into abdominal pockets. Viable M. genitalium persisted in
      the lower genital tract for 8 weeks in three animals, 4 weeks in two, and 1 week
      in one; two primates resisted infection. In both animals inoculated in salpingeal
      pockets, viable M. genitalium was recovered for 2 weeks. Recovery of viable M.
      genitalium from lower genital tract specimens was improved by diluting the
      specimen in broth and by Vero cell coculture. Ascension to upper reproductive
      tract tissues was not detected, even among three persistently infected animals.
      M. genitalium-specific serum antibodies targeting the immunodominant MgpB and
      MgpC proteins appeared within 1 week in three animals inoculated both cervically
      and in salpingeal pockets and in one of three persistently infected animals
      inoculated only in the cervix. M. genitalium-specific IgG, but not IgA, was
      detected in cervical secretions of serum antibody-positive animals, predominantly
      against MgpB and MgpC, but was insufficient to clear M. genitalium lower tract
      infection. Our findings further support female pig-tailed macaques as a model of
      M. genitalium infection, persistence, and immune evasion.

PMID- 27872240
TI  - The Staphylococcus aureus AirSR Two-Component System Mediates Reactive Oxygen
      Species Resistance via Transcriptional Regulation of Staphyloxanthin Production.
AB  - Staphylococcus aureus is an important opportunistic pathogen and is the
      etiological agent of many hospital- and community-acquired infections. The golden
      pigment, staphyloxanthin, of S. aureus colonies distinguishes it from other
      staphylococci and related Gram-positive cocci. Staphyloxanthin is the product of
      a series of biosynthetic steps that produce a unique membrane-embedded C30 golden
      carotenoid and is an important antioxidant. We observed that a strain with an
      inducible airR overexpression cassette had noticeably increased staphyloxanthin
      production compared to the wild-type strain under aerobic culturing conditions.
      Further analysis revealed that depletion or overproduction of the AirR response
      regulator resulted in a corresponding decrease or increase in staphyloxanthin
      production and susceptibility to killing by hydrogen peroxide, respectively.
      Furthermore, the genetic elimination of staphyloxanthin during AirR
      overproduction abolished the protective phenotype of increased staphyloxanthin
      production in a whole-blood survival assay. Promoter reporter and gel shift
      assays determined that the AirR response regulator is a direct positive regulator
      of the staphyloxanthin-biosynthetic operon, crtOPQMN, but is epistatic to
      alternative sigma factor B. Taken together, these data indicate that AirSR
      positively regulates the staphyloxanthin-biosynthetic operon crtOPQMN, promoting
      survival of S. aureus in the presence of oxidants.

PMID- 27872241
TI  - The Type III Effector NleD from Enteropathogenic Escherichia coli Differentiates
      between Host Substrates p38 and JNK.
AB  - Enteropathogenic Escherichia coli (EPEC) is a gastrointestinal pathogen that
      utilizes a type III secretion system (T3SS) to inject an array of virulence
      effector proteins into host enterocytes to subvert numerous cellular processes
      for successful colonization and dissemination. The T3SS effector NleD is a 26-kDa
      zinc metalloprotease that is translocated into host enterocytes, where it
      directly cleaves and inactivates the mitogen-activated protein kinase signaling
      proteins JNK and p38. Here a library of 91 random transposon-based, in-frame,
      linker insertion mutants of NleD were tested for their ability to cleave JNK and
      p38 during transient transfection of cultured epithelial cells. Immunoblot
      analysis of p38 and JNK cleavage showed that 7 mutant derivatives of NleD no
      longer cleaved p38 but maintained the ability to cleave JNK. Site-directed
      mutation of specific regions surrounding the insertion sites within NleD revealed
      that a single amino acid, R203, was essential for cleavage of p38 but not JNK in
      a direct in vitro cleavage assay, in transiently transfected cells, or in EPEC
      infected cells. Mass spectrometry analysis narrowed the cleavage region to within
      residues 187 and 213 of p38. Mutation of residue R203 within NleD to a glutamate
      residue abolished the cleavage of p38 and impaired the ability of NleD to inhibit
      AP-1-dependent gene transcription of a luciferase reporter. Furthermore, the R203
      mutation abrogated the ability of NleD to dampen interleukin-6 production in EPEC
      infected cells. Overall, this work provides greater insight into substrate
      recognition and specificity by the type III effector NleD.

PMID- 27872242
TI  - Systematic Analysis of Two-Component Systems in Citrobacter rodentium Reveals
      Positive and Negative Roles in Virulence.
AB  - Citrobacter rodentium is a murine pathogen used to model intestinal infections
      caused by the human diarrheal pathogens enterohemorrhagic and enteropathogenic
      Escherichia coli During infection, bacteria use two-component systems (TCSs) to
      detect changing environmental cues within the host, allowing for rapid adaptation
      by altering the expression of specific genes. In this study, 26 TCSs were
      identified in C. rodentium, and quantitative PCR (qPCR) analysis showed that they
      are all expressed during murine infection. These TCSs were individually deleted,
      and the in vitro and in vivo effects were analyzed to determine the functional
      consequences. In vitro analyses only revealed minor differences, and
      surprisingly, type III secretion (T3S) was only affected in the DeltaarcA strain.
      Murine infections identified 7 mutants with either attenuated or increased
      virulence. In agreement with the in vitro T3S assay, the DeltaarcA strain was
      attenuated and defective in colonization and cell adherence. The DeltarcsB strain
      was among the most highly attenuated strains. The decrease in virulence of this
      strain may be associated with changes to the cell surface, as Congo red binding
      was altered, and qPCR revealed that expression of the wcaA gene, which has been
      implicated in colanic acid production in other bacteria, was drastically
      downregulated. The DeltauvrY strain exhibited increased virulence compared to the
      wild type, which was associated with a significant increase in bacterial burden
      within the mesenteric lymph nodes. The systematic analysis of virulence
      associated TCSs and investigation of their functions during infection may open
      new avenues for drug development.

PMID- 27872243
TI  - Changing Responses to Changing Seasons: Natural Variation in the Plasticity of
      Flowering Time.

PMID- 27872244
TI  - Network-Guided GWAS Improves Identification of Genes Affecting Free Amino Acids.
AB  - Amino acids are essential for proper growth and development in plants. Amino
      acids serve as building blocks for proteins but also are important for responses
      to stress and the biosynthesis of numerous essential compounds. In seed, the pool
      of free amino acids (FAAs) also contributes to alternative energy, desiccation,
      and seed vigor; thus, manipulating FAA levels can significantly impact a seed's
      nutritional qualities. While genome-wide association studies (GWAS) on branched
      chain amino acids have identified some regulatory genes controlling seed FAAs,
      the genetic regulation of FAA levels, composition, and homeostasis in seeds
      remains mostly unresolved. Hence, we performed GWAS on 18 FAAs from a 313-ecotype
      Arabidopsis (Arabidopsis thaliana) association panel. Specifically, GWAS was
      performed on 98 traits derived from known amino acid metabolic pathways (approach
      1) and then on 92 traits generated from an unbiased correlation-based metabolic
      network analysis (approach 2), and the results were compared. The latter approach
      facilitated the discovery of additional novel metabolic interactions and single
      nucleotide polymorphism-trait associations not identified by the former approach.
      The most prominent network-guided GWAS signal was for a histidine (His)-related
      trait in a region containing two genes: a cationic amino acid transporter (CAT4)
      and a polynucleotide phosphorylase resistant to inhibition with fosmidomycin. A
      reverse genetics approach confirmed CAT4 to be responsible for the natural
      variation of His-related traits across the association panel. Given that His is a
      semiessential amino acid and a potent metal chelator, CAT4 orthologs could be
      considered as candidate genes for seed quality biofortification in crop plants.

PMID- 27872245
TI  - The Transcription Factor ATHB5 Affects GA-Mediated Plasticity in Hypocotyl Cell
      Growth during Seed Germination.
AB  - Gibberellic acid (GA)-mediated cell expansion initiates the seed-to-seedling
      transition in plants and is repressed by DELLA proteins. Using digital single
      cell analysis, we identified a cellular subdomain within the midhypocotyl, whose
      expansion drives the final step of this developmental transition under optimal
      conditions. Using network inference, the transcription factor ATHB5 was
      identified as a genetic factor whose localized expression promotes GA-mediated
      expansion specifically within these cells. Both this protein and its putative
      growth-promoting target EXPANSIN3 are repressed by DELLA, and coregulated at
      single-cell resolution during seed germination. The cellular domains of hormone
      sensitivity were explored within the Arabidopsis (Arabidopsis thaliana) embryo by
      putting seeds under GA-limiting conditions and quantifying cellular growth
      responses. The middle and upper hypocotyl have a greater requirement for GA to
      promote cell expansion than the lower embryo axis. Under these conditions,
      germination was still completed following enhanced growth within the radicle and
      lower axis. Under GA-limiting conditions, the athb5 mutant did not show a
      phenotype at the level of seed germination, but it did at a cellular level with
      reduced cell expansion in the hypocotyl relative to the wild type. These data
      reveal that the spatiotemporal cell expansion events driving this transition are
      not determinate, and the conditional use of GA-ATHB5-mediated hypocotyl growth
      under optimal conditions may be used to optionally support rapid seedling growth.
      This study demonstrates that multiple genetic and spatiotemporal cell expansion
      mechanisms underlie the seed to seedling transition in Arabidopsis.

PMID- 27872248
TI  - Rac and Rho compete to cooperate.

PMID- 27872249
TI  - Job Dekker: Hitting the scientific hi-Cs.

PMID- 27872246
TI  - SHADE AVOIDANCE 4 Is Required for Proper Auxin Distribution in the Hypocotyl.
AB  - The phytohormone auxin is involved in virtually every aspect of plant growth and
      development. Through polar auxin transport, auxin gradients can be established,
      which then direct plant differentiation and growth. Shade avoidance responses are
      well-known processes that require polar auxin transport. In this study, we have
      identified a mutant, shade avoidance 4 (sav4), defective in shade-induced
      hypocotyl elongation and basipetal auxin transport. SAV4 encodes an unknown
      protein with armadillo repeat- and tetratricopeptide repeat-like domains known to
      provide protein-protein interaction surfaces. C terminally yellow fluorescent
      protein-tagged SAV4 localizes to both the plasma membrane and the nucleus.
      Membrane-localized SAV4 displays a polar association with the shootward plasma
      membrane domain in hypocotyl and root cells, which appears to be necessary for
      its function in hypocotyl elongation. Cotransfection of SAV4 and ATP-binding
      cassette B1 (ABCB1) auxin transporter in tobacco (Nicotiana benthamiana) revealed
      that SAV4 blocks ABCB1-mediated auxin efflux. We thus propose that polarly
      localized SAV4 acts to inhibit ABCB-mediated auxin efflux toward shoots and
      facilitates the establishment of proper auxin gradients.

PMID- 27872250
TI  - Axon degeneration: Linking axonal bioenergetics to myelin.
AB  - The mechanisms by which axonal degeneration occurs, even in the presence of
      apparently normal myelin sheaths, remain unknown. In this issue, Yin et al.
      (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201607099) study mutant mice in
      which proteolipid protein is replaced by the peripheral myelin protein P0 and
      describe a number of early axonal abnormalities, which together suggest that
      aberrant mitochondrial energy metabolism precedes axonal degeneration.

PMID- 27872247
TI  - Two Membrane-Anchored Aspartic Proteases Contribute to Pollen and Ovule
      Development.
AB  - Aspartic proteases are a class of proteolytic enzymes with conserved aspartate
      residues, which are implicated in protein processing, maturation, and
      degradation. Compared with yeast and animals, plants possess a larger aspartic
      protease family. However, little is known about most of these enzymes. Here, we
      characterized two Arabidopsis (Arabidopsis thaliana) putative
      glycosylphosphatidylinositol (GPI)-anchored aspartic protease genes, A36 and A39,
      which are highly expressed in pollen and pollen tubes. a36 and a36 a39 mutants
      display significantly reduced pollen activity. Transmission electron microscopy
      and terminal-deoxynucleotidyl transferase-mediated nick end labeling assays
      further revealed that the unviable pollen in a36 a39 may undergo unanticipated
      apoptosis-like programmed cell death. The degeneration of female gametes also
      occurred in a36 a39 Aniline Blue staining, scanning electron microscopy, and semi
      in vitro guidance assays indicated that the micropylar guidance of pollen tubes
      is significantly compromised in a36 a39 A36 and A39 that were fused with green
      fluorescent protein are localized to the plasma membrane and display punctate
      cytosolic localization and colocalize with the GPI-anchored protein COBRA-LIKE10.
      Furthermore, in a36 a39, the abundance of highly methylesterified
      homogalacturonans and xyloglucans was increased significantly in the apical
      pollen tube wall. These results indicate that A36 and A39, two putative GPI
      anchored aspartic proteases, play important roles in plant reproduction in
      Arabidopsis.

PMID- 27872251
TI  - Regulation of EGFR surface levels by COPII-dependent trafficking.
AB  - Cell surface levels of epidermal growth factor receptors (EGFRs) are thought to
      be controlled mainly by endocytic trafficking, with biosynthetic EGFR trafficking
      presumed to be a constitutive and unregulated process. However, Scharaw et al.
      (2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201601090) demonstrate a role
      for inducible COPII trafficking in controlling EGFR surface levels.

PMID- 27872253
TI  - GTPase cross talk regulates TRAPPII activation of Rab11 homologues during vesicle
      biogenesis.
AB  - Rab guanosine triphosphatases (GTPases) control cellular trafficking pathways by
      regulating vesicle formation, transport, and tethering. Rab11 and its paralogs
      regulate multiple secretory and endocytic recycling pathways, yet the guanine
      nucleotide exchange factor (GEF) that activates Rab11 in most eukaryotic cells is
      unresolved. The large multisubunit transport protein particle (TRAPP) II complex
      has been proposed to act as a GEF for Rab11 based on genetic evidence, but
      conflicting biochemical experiments have created uncertainty regarding Rab11
      activation. Using physiological Rab-GEF reconstitution reactions, we now provide
      definitive evidence that TRAPPII is a bona fide GEF for the yeast Rab11
      homologues Ypt31/32. We also uncover a direct role for Arf1, a distinct GTPase,
      in recruiting TRAPPII to anionic membranes. Given the known role of Ypt31/32 in
      stimulating activation of Arf1, a bidirectional cross talk mechanism appears to
      drive biogenesis of secretory and endocytic recycling vesicles. By coordinating
      simultaneous activation of two essential GTPase pathways, this mechanism ensures
      recruitment of the complete set of effectors needed for vesicle formation,
      transport, and tethering.

PMID- 27872252
TI  - Integrin-mediated mechanotransduction.
AB  - Cells can detect and react to the biophysical properties of the extracellular
      environment through integrin-based adhesion sites and adapt to the extracellular
      milieu in a process called mechanotransduction. At these adhesion sites,
      integrins connect the extracellular matrix (ECM) with the F-actin cytoskeleton
      and transduce mechanical forces generated by the actin retrograde flow and myosin
      II to the ECM through mechanosensitive focal adhesion proteins that are
      collectively termed the "molecular clutch." The transmission of forces across
      integrin-based adhesions establishes a mechanical reciprocity between the
      viscoelasticity of the ECM and the cellular tension. During mechanotransduction,
      force allosterically alters the functions of mechanosensitive proteins within
      adhesions to elicit biochemical signals that regulate both rapid responses in
      cellular mechanics and long-term changes in gene expression. Integrin-mediated
      mechanotransduction plays important roles in development and tissue homeostasis,
      and its dysregulation is often associated with diseases.

PMID- 27872254
TI  - A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal
      vesicle biogenesis.
AB  - Saccharomyces cerevisiae contains three conserved reticulon and reticulon-like
      proteins that help maintain ER structure by stabilizing high membrane curvature
      in ER tubules and the edges of ER sheets. A mutant lacking all three proteins has
      dramatically altered ER morphology. We found that ER shape is restored in this
      mutant when Pex30p or its homologue Pex31p is overexpressed. Pex30p can tubulate
      membranes both in cells and when reconstituted into proteoliposomes, indicating
      that Pex30p is a novel ER-shaping protein. In contrast to the reticulons, Pex30p
      is low abundance, and we found that it localizes to subdomains in the ER. We show
      that these ER subdomains are the sites where most preperoxisomal vesicles (PPVs)
      are generated. In addition, overproduction or deletion of Pex30p or Pex31p alters
      the size, shape, and number of PPVs. Our findings suggest that Pex30p and Pex31p
      help shape and generate regions of the ER where PPV biogenesis occurs.

PMID- 27872255
TI  - Proteolipid protein-deficient myelin promotes axonal mitochondrial dysfunction
      via altered metabolic coupling.
AB  - Hereditary spastic paraplegia (HSP) is a neurological syndrome characterized by
      degeneration of central nervous system (CNS) axons. Mutated HSP proteins include
      myelin proteolipid protein (PLP) and axon-enriched proteins involved in
      mitochondrial function, smooth endoplasmic reticulum (SER) structure, and
      microtubule (MT) stability/function. We characterized axonal mitochondria, SER,
      and MTs in rodent optic nerves where PLP is replaced by the peripheral nerve
      myelin protein, P0 (P0-CNS mice). Mitochondrial pathology and degeneration were
      prominent in juxtaparanodal axoplasm at 1 mo of age. In wild-type (WT) optic
      nerve axons, 25% of mitochondria-SER associations occurred on extensions of the
      mitochondrial outer membrane. Mitochondria-SER associations were reduced by 86%
      in 1-mo-old P0-CNS juxtaparanodal axoplasm. 1-mo-old P0-CNS optic nerves were
      more sensitive to oxygen-glucose deprivation and contained less adenosine
      triphosphate (ATP) than WT nerves. MT pathology and paranodal axonal ovoids were
      prominent at 6 mo. These data support juxtaparanodal mitochondrial degeneration,
      reduced mitochondria-SER associations, and reduced ATP production as causes of
      axonal ovoid formation and axonal degeneration.

PMID- 27872256
TI  - The endosomal transcriptional regulator RNF11 integrates degradation and
      transport of EGFR.
AB  - Stimulation of cells with epidermal growth factor (EGF) induces internalization
      and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway.
      For continuous cell functioning, EGFR plasma membrane levels are maintained by
      transporting newly synthesized EGFRs to the cell surface. The regulation of this
      process is largely unknown. In this study, we find that EGF stimulation
      specifically increases the transport efficiency of newly synthesized EGFRs from
      the endoplasmic reticulum to the plasma membrane. This coincides with an up
      regulation of the inner coat protein complex II (COPII) components SEC23B,
      SEC24B, and SEC24D, which we show to be specifically required for EGFR transport.
      Up-regulation of these COPII components requires the transcriptional regulator
      RNF11, which localizes to early endosomes and appears additionally in the cell
      nucleus upon continuous EGF stimulation. Collectively, our work identifies a new
      regulatory mechanism that integrates the degradation and transport of EGFR in
      order to maintain its physiological levels at the plasma membrane.

PMID- 27872258
TI  - Bipolar At-Risk Criteria: An Examination of Which Clinical Features Have Optimal
      Utility for Identifying Youth at Risk of Early Transition From Depression to
      Bipolar Disorders.
AB  - Background: A clinical and research challenge is to identify which depressed
      youth are at risk of "early transition to bipolar disorders (ET-BD)." This 2-part
      study (1) examines the clinical utility of previously reported BD at-risk (BAR)
      criteria in differentiating ET-BD cases from unipolar depression (UP) controls;
      and (2) estimates the Number Needed to Screen (NNS) for research and general
      psychiatry settings. Methods: Fifty cases with reliably ascertained, ET-BD I and
      II cases were matched for gender and birth year with 50 UP controls who did not
      develop BD over 2 years. We estimated the clinical utility for finding true cases
      and screening out non-cases for selected risk factors and their NNS. Using a
      convenience sample (N = 80), we estimated the NNS when adjustments were made to
      account for data missing from clinical case notes. Results: Sub-threshold mania,
      cyclothymia, family history of BD, atypical depression symptoms and probable
      antidepressant-emergent elation, occurred significantly more frequently in ET-BD
      youth. Each of these "BAR-Depression" criteria demonstrated clinical utility for
      screening out non-cases. Only cyclothymia demonstrated good utility for case
      finding in research settings; sub-threshold mania showed moderate utility. In the
      convenience sample, the NNS for each criterion ranged from ~4 to 7. Conclusions:
      Cyclothymia showed the optimum profile for case finding, screening and NNS in
      research settings. However, its presence or absence was only reported in 50% of
      case notes. Future studies of ET-BD instruments should distinguish which criteria
      have clinical utility for case finding vs screening.

PMID- 27872257
TI  - Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric
      Populations: A Systematic Review and Meta-analysis.
AB  - Schizophrenia is characterized by neuropsychological deficits across many
      cognitive domains. Cognitive phenotypes with high heritability and genetic
      overlap with schizophrenia liability can help elucidate the mechanisms leading
      from genes to psychopathology. We performed a meta-analysis of 170 published twin
      and family heritability studies of >800 000 nonpsychiatric and schizophrenia
      subjects to accurately estimate heritability across many neuropsychological tests
      and cognitive domains. The proportion of total variance of each phenotype due to
      additive genetic effects (A), shared environment (C), and unshared environment
      and error (E), was calculated by averaging A, C, and E estimates across studies
      and weighting by sample size. Heritability ranged across phenotypes, likely due
      to differences in genetic and environmental effects, with the highest
      heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%),
      Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while
      the lowest heritability was observed for Executive Function (20%-40%). These
      results confirm that many cognitive phenotypes are under strong genetic
      influences. Heritability estimates were comparable in nonpsychiatric and
      schizophrenia samples, suggesting that environmental factors and illness-related
      moderators (eg, medication) do not substantially decrease heritability in
      schizophrenia samples, and that genetic studies in schizophrenia samples are
      informative for elucidating the genetic basis of cognitive deficits. Substantial
      genetic overlap between cognitive phenotypes and schizophrenia liability (average
      rg = -.58) in twin studies supports partially shared genetic etiology. It will be
      important to conduct comparative studies in well-powered samples to determine
      whether the same or different genes and genetic variants influence cognition in
      schizophrenia patients and the general population.

PMID- 27872261
TI  - Comorbid Diabetes and Depression in a National Sample of Adults With Psychosis.
AB  - Objective: People with psychosis have an elevated risk of depression and diabetes
      but no large-scale study has characterized their relationship. We aimed to assess
      this association and to evaluate possible explanatory factors. Methods: Analysis
      of cross-sectional data from a national sample of 1155 people with psychosis who
      gave a fasting blood sample and could be tested for diabetes mellitus. The
      association between current diabetes mellitus and current depression was
      estimated using logistic regression, adjusted for age, sex and current
      psychotropic medication. Results: A diagnosis of depression was significantly
      associated with diabetes (OR = 2.16, P = .048) and diabetes medication (OR =
      2.50, P = .050) in people with schizophrenia but no other psychosis subtype.
      Adjustment for cognitive processing speed and current residence (especially
      psychiatric hospitalization) attenuated that association to nonsignificance.
      Diabetes and diabetes medication were not significantly associated with
      antidepressant or mood stabilizer medication. Conclusions: Clinicians should be
      aware that people with schizophrenia and diabetes have twice the rate of current
      depression, and that comorbid diabetes and depression is associated with
      cognitive impairment and hospitalization. Efforts to disentangle the causal
      pathways between diabetes, depression, and cognition in people with schizophrenia
      may be complicated by multiple indications in people with psychosis for the
      prescription of depression medication, and their lack of association with
      diabetes mellitus.

PMID- 27872263
TI  - Isolation and Intellect-A Letter and Selected Works by Walter K. Delbridge.

PMID- 27872262
TI  - From Perception to Thought: A Phenomenological Approach to Hallucinatory
      Experience.

PMID- 27872259
TI  - Hallucinations: A Systematic Review of Points of Similarity and Difference Across
      Diagnostic Classes.
AB  - Hallucinations constitute one of the 5 symptom domains of psychotic disorders in
      DSM-5, suggesting diagnostic significance for that group of disorders. Although
      specific featural properties of hallucinations (negative voices, talking in the
      third person, and location in external space) are no longer highlighted in DSM,
      there is likely a residual assumption that hallucinations in schizophrenia can be
      identified based on these candidate features. We investigated whether certain
      featural properties of hallucinations are specifically indicative of
      schizophrenia by conducting a systematic review of studies showing direct
      comparisons of the featural and clinical characteristics of (auditory and visual)
      hallucinations among 2 or more population groups (one of which included
      schizophrenia). A total of 43 articles were reviewed, which included
      hallucinations in 4 major groups (nonclinical groups, drug- and alcohol-related
      conditions, medical and neurological conditions, and psychiatric disorders). The
      results showed that no single hallucination feature or characteristic uniquely
      indicated a diagnosis of schizophrenia, with the sole exception of an age of
      onset in late adolescence. Among the 21 features of hallucinations in
      schizophrenia considered here, 95% were shared with other psychiatric disorders,
      85% with medical/neurological conditions, 66% with drugs and alcohol conditions,
      and 52% with the nonclinical groups. Additional differences rendered the
      nonclinical groups somewhat distinctive from clinical disorders. Overall, when
      considering hallucinations, it is inadvisable to give weight to the presence of
      any featural properties alone in making a schizophrenia diagnosis. It is more
      important to focus instead on the co-occurrence of other symptoms and the value
      of hallucinations as an indicator of vulnerability.

PMID- 27872265
TI  - Disclosing My Diagnosis.

PMID- 27872260
TI  - Familial Aggregation and Heritability of Schizophrenia and Co-aggregation of
      Psychiatric Illnesses in Affected Families.
AB  - Strong familial aggregation of schizophrenia has been reported but there is
      uncertainty concerning the degree of genetic contribution to the phenotypic
      variance of the disease. This study aimed to examine the familial aggregation and
      heritability of schizophrenia, and the relative risks (RRs) of other psychiatric
      diseases, in relatives of people with schizophrenia using the Taiwan National
      Health Insurance Database. The study population included individuals with
      affected first-degree or second-degree relatives identified from all
      beneficiaries (n = 23 422 955) registered in 2013. Diagnoses of schizophrenia
      made by psychiatrists were ascertained between January 1, 1996 and December 31,
      2013. Having an affected co-twin, first-degree relative, second-degree relative,
      or spouse was associated with an adjusted RR (95% CI) of 37.86 (30.55-46.92),
      6.30 (6.09-6.53), 2.44 (1.91-3.12), and 1.88 (1.64-2.15), respectively. Compared
      with the general population, individuals with one affected first-degree relative
      had a RR (95% CI) of 6.00 (5.79-6.22) and those with 2 or more had a RR (95% CI)
      of 14.66 (13.00-16.53) for schizophrenia. The accountability for the phenotypic
      variance of schizophrenia was 47.3% for genetic factors, 15.5% for shared
      environmental factors, and 37.2% for non-shared environmental factors. The RR
      (95% CI) in individuals with a first-degree relative with schizophrenia was 3.49
      (3.34-3.64) for mood disorders and 3.91 (3.35-4.57) for delusional disorders. A
      family history of schizophrenia is therefore associated with a higher risk of
      developing schizophrenia, mood disorders, and delusional disorders. Heritability
      and environmental factors each account for half of the phenotypic variance of
      schizophrenia.

PMID- 27872264
TI  - Current Approaches to Studying Hallucinations: Overcoming Barriers to Progress.

PMID- 27872266
TI  - Diversity Within the Psychotic Continuum.
AB  - There has been great interest in the hallucination-like events experienced by the
      general nonclinical population. Many psychiatric scientists have come to identify
      these as part of a "psychotic continuum" and have begun to ask what we might
      learn from these experiences that will enable us to better understand and treat
      psychosis. While sympathetic to this goal, this paper argues that many of these
      events in the nonclinical population may be associated with the attention to
      inner imagery characteristic of much religious practice like unscripted prayer.
      Many of these hallucination-like events are phenomenologically distinct,
      culturally salient, and are predicted both by a measure of absorption, which
      probes for an interest in inner imagery, and by inner sense cultivation practice.
      These observations suggest that rare, brief, and positive sensory events may not
      be associated with psychotic vulnerability. They also suggest there may be an
      absorption-dissociation pathway, with or without trauma, for more frequent
      hallucinations.

PMID- 27872267
TI  - Endophenotypes, Epigenetics, Polygenicity and More: Irv Gottesman's Dynamic
      Legacy.
AB  - First, we describe the hallmark contributions of Irv Gottesman's pioneering
      scholarship for schizophrenia research including concepts of polygenicity, gene *
      environment interactions, epigenetics and the endophenotype concept. Gottesman
      and colleagues' twin studies showed that genes, not social factors, mediate
      schizophrenia risk. He then showed that schizophrenia is highly polygenic. Next,
      he introduced the concept of epigenetics into schizophrenia research. Gottesman
      then introduced the quantitative endophenotype concept. Endophenotypes are
      laboratory-based measures that show deficits in schizophrenia patients and lesser
      deficits in their first degree "unaffected" relatives and are viewed as being
      more proximal to genes and having a simpler genetic architecture than are "fuzzy"
      qualitative diagnostic disorders. Endophenotypes offer an exciting path to gene
      discovery, neural circuits, genetic architecture and new treatment pathways of
      schizophrenia and related psychotic disorders. Second, we were asked to discuss 2
      of many endophenotype Consortia and related studies, in order to illustrate the
      impact of Gottesman's work. We describe the Consortium on the Genetics of
      Schizophrenia (COGS) exploring neurocognitive and neurophysiological
      endophenotypes in family and case-control studies. Association, linkage,
      sequencing and epigenetic studies are described. The Bipolar and Schizophrenia
      Network for Intermediate Phenotypes (BSNIP) uses an array of endophenotypes
      including brain imaging in studies across the psychosis dimension, allowing for
      dimensional analyses. BSNIP results have led to the concept of biotypes,
      advancing the field. Irv Gottesman was imaginatively prescient in generating
      novel insights and predicting many major issues which challenge schizophrenia
      researchers who still use his concepts to guide current research approaches.

PMID- 27872268
TI  - Consistent Functional Connectivity Alterations in Schizophrenia Spectrum
      Disorder: A Multisite Study.
AB  - Schizophrenia (SZ) is a severe mental illness with high heritability and complex
      etiology. Mounting evidence from neuroimaging has implicated disrupted brain
      network connectivity in the pathophysiology. However, previous findings are
      inconsistent, likely due to a combination of methodological and clinical
      variability and relatively small sample sizes. Few studies have used a data
      driven approach for characterizing pathological interactions between regions in
      the whole brain and evaluated the generalizability across independent samples. To
      overcome this issue, we collected resting-state functional magnetic resonance
      imaging data from 3 independent samples (1 from Norway and 2 from Sweden)
      consisting of 182 persons with a SZ spectrum diagnosis and 348 healthy controls.
      We used a whole-brain data-driven definition of network nodes and regularized
      partial correlations to evaluate and compare putatively direct brain network node
      interactions between groups. The clinical utility of the functional connectivity
      features and the generalizability of effects across samples were evaluated by
      training and testing multivariate classifiers in the independent samples using
      machine learning. Univariate analyses revealed 14 network edges with consistent
      reductions in functional connectivity encompassing frontal, somatomotor, visual,
      auditory, and subcortical brain nodes in patients with SZ. We found a high
      overall accuracy in classifying patients and controls (up to 80%) using
      independent training and test samples, strongly supporting the generalizability
      of connectivity alterations across different scanners and heterogeneous samples.
      Overall, our findings demonstrate robust reductions in functional connectivity in
      SZ spectrum disorders, indicating disrupted information flow in sensory,
      subcortical, and frontal brain regions.

PMID- 27872271
TI  - Effects of a change in entry-to-practice criteria for cardiovascular perfusion in
      Canada: results of a national survey.
AB  - INTRODUCTION: Years of experience and level of education are two important
      determinants of a clinician's expertise. While entry-to-practice criteria for
      admission to perfusion training in Canada changed from clinical experience-based
      criteria to education-based criteria in 2006, the effects of these changes have
      not been studied. OBJECTIVE: To determine the academic and clinical backgrounds
      of perfusionists in Canada, ascertain perceptions about the adequacy of training
      and evaluate the effects of the changes on the composition of the perfusion
      community of Canada. METHODS: An electronic questionnaire was distributed to all
      practicing perfusionists in Canada, addressing details regarding clinical
      experience, academic education and perceptions about the adequacy of training.
      RESULTS: Two hundred and twenty-eight questionnaires were completed, representing
      a 72% response rate. Perfusionists admitted under academic-based criteria have
      significantly higher levels of education (100% degree holders vs 69.1%, p<0.001),
      but less antecedent clinical training and experience (median, IQR: 0, 0 - 4.5
      years vs 2, 2 - 8 years, p<0.0001), are younger (median age range 31-35 years vs
      51-55 years, p<0.0001), more likely to be female (58.7% vs 41.3%, p=0.006) and
      are significantly more likely to enter perfusion because of attraction to the
      type of work (p=0.045). Many perfusionists (70, 32%) in Canada believe themselves
      inadequately trained for their clinical assignments outside the OR. In addition,
      19% of perfusionists plan to retire over the next 10 years. CONCLUSIONS: The
      introduction of education-based entry criteria has changed the academic and
      clinical experience levels of perfusionists in Canada. Strategies designed to
      better prepare perfusionists for their clinical assignments outside the OR are
      merited.

PMID- 27872269
TI  - Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential
      Endophenotype of Compulsive Neuropsychiatric Disorders.
AB  - Psychogenic polydipsia, which is compulsive, non-regulatory fluid consumption, is
      present in 6%-20% of chronic psychiatric patients and frequently associated with
      the schizophrenia diagnosis. In the present study, we investigated the relation
      between schizophrenia-like symptoms and biomarkers with a compulsive drinking
      behavior phenotype in rats. Rats that were selected for low drinking vs high
      drinking behavior following schedule-induced polydipsia (SIP) were assessed in a
      latent inhibition (LI) paradigm using tone and electrical foot shock and in a
      spatial reversal learning task to evaluate behavioral inflexibility. We also
      analyzed the myelin basic protein in different brain areas of high drinker (HD)
      and low drinker (LD) rats. The HD rats, which were characterized by a compulsive
      drinking behavior on SIP, had a reduced level of LI effect and increased
      behavioral inflexibility in the spatial reversal learning task in comparison to
      the LD group. Moreover, HD rats showed less myelination in the center of the
      corpus callosum, striatum, and amygdala in comparison to LD rats. These findings
      strengthen the validity of HD rats that were selected by SIP as a possible
      phenotype of compulsive neuropsychiatric disorders, as evidenced by the existence
      of behaviors and biological markers that are related to schizophrenia and
      obsessive-compulsive disorder, including a reduced LI effect, behavioral
      inflexibility and reduced brain myelination. Future studies could contribute to
      the elucidation of the mechanisms underlying the compulsive phenotype of HD rats
      and its relation to vulnerability to schizophrenia.

PMID- 27872272
TI  - Oxygenator failure in acute myeloid leukaemia. A case report.
AB  - Extracorporeal membrane oxygenation (ECMO) therapy can be used to rescue patients
      who develop respiratory failure with acute myeloid leukaemia. We describe a
      unique case of rapid failure of an oxygenator on ECMO, secondary to high
      leukocyte count and cell lysis in an adult patient with acute myeloid leukaemia.

PMID- 27872273
TI  - "What's Cooking?": Qualitative Evaluation of a Head Start Parent-Child Pilot
      Cooking Program.
AB  - Providing access to nutritious foods is crucial for low-income populations, but
      increasing nutrition-related skills and attitudes such as food preparation,
      feeding practices, and positive perceptions around healthy foods to establish
      sustainable behavior change are paramount for the development of healthy
      lifestyles. This qualitative study was designed to evaluate the What's Cooking
      pilot program. A total of 15 participants were recruited from two Head Start
      schools through flyers, text messages, and e-mails. Two focus group sessions were
      audiotaped to obtain information related to the program implementation and
      perceived outcomes and behavior change. Recordings of the sessions were
      transcribed and analyzed using constant comparative analysis. Resulting themes
      included children's asking behavior for healthy foods, family connection, parent
      comfort in cooking, and development of child attitude, knowledge, and skills. The
      qualitative analysis provided foundational information for the development of a
      framework for other nutrition program providers to understand the role of the
      child in a cooking class as a mediator for lifestyle change. The What's Cooking
      program increased the implementation of sustainable food practices and healthy
      nutrition behaviors through educating families on how to involve their children
      in positive mealtime practices.

PMID- 27872270
TI  - HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling
      Pathways.
AB  - Sensory neuropathies are the most common neurological complication of HIV. Of
      these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection
      and characterized by length-dependent axonal degeneration of dorsal root ganglion
      (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but
      recent experiments revealed that the HIV glycoprotein gp120 is internalized and
      localized within axons of DRG neurons. Based on these findings, we investigated
      whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular
      process critical for appropriate maintenance of the axonal compartment.
      Significantly, we found that gp120 severely impaired both anterograde and
      retrograde FAT. Providing a mechanistic basis for these effects, pharmacological
      experiments revealed an involvement of various phosphotransferases in this toxic
      effect, including members of mitogen-activated protein kinase pathways (Tak-1,
      p38, and c-Jun N-terminal Kinase (JNK)), inhibitor of kappa-B-kinase 2 (IKK2),
      and PP1. Biochemical experiments and axonal outgrowth assays in cell lines and
      primary cultures extended these findings. Impairments in neurite outgrowth in DRG
      neurons by gp120 were rescued using a Tak-1 inhibitor, implicating a Tak-1
      mitogen-activated protein kinase pathway in gp120 neurotoxicity. Taken together,
      these observations indicate that kinase-based impairments in FAT represent a
      novel mechanism underlying gp120 neurotoxicity consistent with the dying-back
      degeneration seen in DSP. Targeting gp120-based impairments in FAT with specific
      kinase inhibitors might provide a novel therapeutic strategy to prevent axonal
      degeneration in DSP.

PMID- 27872274
TI  - Voices Through Cameras.
AB  - Engaging and empowering youth to promote health could be important in promoting
      sustainable positive behaviors. Photovoice is a community-based participatory
      research tool giving priority populations opportunities for active community
      engagement and advocacy through photography. Our project objective was to better
      understand youth perceptions related to food justice within their own community
      and identify solutions to promote positive change, using photovoice. Twelve
      minority youth from a low-income New York City neighborhood participated. Six
      photovoice sessions were conducted within a 24-week after-school food justice
      program, which included three photo assignments aimed at answering, "What
      influences me to eat healthy and unhealthy in my community and home environment?"
      Photos guided interviews and discussions. Inductive and deductive processes were
      used to identify codes; similar codes were grouped into themes. Five major themes
      emerged from the data: (1) attitudes toward food industry and food safety, (2)
      environmental influences of food choices, (3) social influences of food choices,
      (4) diet impact on health and well-being, and (5) solutions to improve the food
      environment. Participants shared their photos with community members at a
      celebration/photo exhibit. Photovoice could be a useful tool for youth to reflect
      on their food environment and engage in promoting positive change within their
      community.

PMID- 27872275
TI  - Serving Those That Serve.
AB  - Since 1986, health promotion has had a place within the U.S. Department of
      Defense. Emphasizing the leading health indicators of Healthy People, the role of
      health promotion has continued to support the U.S. Armed Forces in perhaps one of
      the most challenging decades of wartime operations. Serving a sizable population
      with both typical and mission-related health issues, health promotion plays a
      critical role in maintaining and improving health. The purpose of this article is
      to highlight military health promotion by offering insight into the day-to-day
      life of a "boots on the ground" military health educator, reviewing the
      challenges and opportunities of working with a unique population. A summary of a
      variety of military specific initiatives is provided. Additionally, the article
      highlights the barriers and benefits to military health promotion. Last, the
      article concludes with a call to action to consider the role of all health
      educators in serving those that serve.

PMID- 27872276
TI  - Profile of Peter A. Jones.

PMID- 27872277
TI  - An oligotrophic deep-subsurface community dependent on syntrophy is dominated by
      sulfur-driven autotrophic denitrifiers.
AB  - Subsurface lithoautotrophic microbial ecosystems (SLiMEs) under oligotrophic
      conditions are typically supported by H2 Methanogens and sulfate reducers, and
      the respective energy processes, are thought to be the dominant players and have
      been the research foci. Recent investigations showed that, in some deep, fluid
      filled fractures in the Witwatersrand Basin, South Africa, methanogens contribute
      <5% of the total DNA and appear to produce sufficient CH4 to support the rest of
      the diverse community. This paradoxical situation reflects our lack of knowledge
      about the in situ metabolic diversity and the overall ecological trophic
      structure of SLiMEs. Here, we show the active metabolic processes and
      interactions in one of these communities by combining metatranscriptomic
      assemblies, metaproteomic and stable isotopic data, and thermodynamic modeling.
      Dominating the active community are four autotrophic beta-proteobacterial genera
      that are capable of oxidizing sulfur by denitrification, a process that was
      previously unnoticed in the deep subsurface. They co-occur with sulfate reducers,
      anaerobic methane oxidizers, and methanogens, which each comprise <5% of the
      total community. Syntrophic interactions between these microbial groups remove
      thermodynamic bottlenecks and enable diverse metabolic reactions to occur under
      the oligotrophic conditions that dominate in the subsurface. The dominance of
      sulfur oxidizers is explained by the availability of electron donors and
      acceptors to these microorganisms and the ability of sulfur-oxidizing
      denitrifiers to gain energy through concomitant S and H2 oxidation. We
      demonstrate that SLiMEs support taxonomically and metabolically diverse
      microorganisms, which, through developing syntrophic partnerships, overcome
      thermodynamic barriers imposed by the environmental conditions in the deep
      subsurface.

PMID- 27872278
TI  - Reconstitution of a Mycobacterium tuberculosis proteostasis network highlights
      essential cofactor interactions with chaperone DnaK.
AB  - During host infection, Mycobacterium tuberculosis (Mtb) encounters several types
      of stress that impair protein integrity, including reactive oxygen and nitrogen
      species and chemotherapy. The resulting protein aggregates can be resolved or
      degraded by molecular machinery conserved from bacteria to eukaryotes. Eukaryotic
      Hsp104/Hsp70 and their bacterial homologs ClpB/DnaK are ATP-powered chaperones
      that restore toxic protein aggregates to a native folded state. DnaK is essential
      in Mycobacterium smegmatis, and ClpB is involved in asymmetrically distributing
      damaged proteins during cell division as a mechanism of survival in Mtb,
      commending both proteins as potential drug targets. However, their molecular
      partners in protein reactivation have not been characterized in mycobacteria.
      Here, we reconstituted the activities of the Mtb ClpB/DnaK bichaperone system
      with the cofactors DnaJ1, DnaJ2, and GrpE and the small heat shock protein Hsp20.
      We found that DnaJ1 and DnaJ2 activate the ATPase activity of DnaK differently. A
      point mutation in the highly conserved HPD motif of the DnaJ proteins abrogates
      their ability to activate DnaK, although the DnaJ2 mutant still binds to DnaK.
      The purified Mtb ClpB/DnaK system reactivated a heat-denatured model substrate,
      but the DnaJ HPD mutants inhibited the reaction. Finally, either DnaJ1 or DnaJ2
      is required for mycobacterial viability, as is the DnaK-activating activity of a
      DnaJ protein. These studies lay the groundwork for strategies to target essential
      chaperone-protein interactions in Mtb, the leading cause of death from a
      bacterial infection.

PMID- 27872280
TI  - Graphene oxide-based efficient and scalable solar desalination under one sun with
      a confined 2D water path.
AB  - Because it is able to produce desalinated water directly using solar energy with
      minimum carbon footprint, solar steam generation and desalination is considered
      one of the most important technologies to address the increasingly pressing
      global water scarcity. Despite tremendous progress in the past few years,
      efficient solar steam generation and desalination can only be achieved for rather
      limited water quantity with the assistance of concentrators and thermal
      insulation, not feasible for large-scale applications. The fundamental paradox is
      that the conventional design of direct absorber-bulk water contact ensures
      efficient energy transfer and water supply but also has intrinsic thermal loss
      through bulk water. Here, enabled by a confined 2D water path, we report an
      efficient (80% under one-sun illumination) and effective (four orders salinity
      decrement) solar desalination device. More strikingly, because of minimized heat
      loss, high efficiency of solar desalination is independent of the water quantity
      and can be maintained without thermal insulation of the container. A foldable
      graphene oxide film, fabricated by a scalable process, serves as efficient solar
      absorbers (>94%), vapor channels, and thermal insulators. With unique structure
      designs fabricated by scalable processes and high and stable efficiency achieved
      under normal solar illumination independent of water quantity without any
      supporting systems, our device represents a concrete step for solar desalination
      to emerge as a complementary portable and personalized clean water solution.

PMID- 27872279
TI  - Role of the receptor Mas in macrophage-mediated inflammation in vivo.
AB  - Recently, an alternative renin-angiotensin system pathway has been described,
      which involves binding of angiotensin-(1-7) to its receptor Mas. The Mas axis may
      counterbalance angiotensin-II-mediated proinflammatory effects, likely by
      affecting macrophage function. Here we investigate the role of Mas in murine
      models of autoimmune neuroinflammation and atherosclerosis, which both involve
      macrophage-driven pathomechanisms. Mas signaling affected macrophage
      polarization, migration, and macrophage-mediated T-cell activation. Mas
      deficiency exacerbated the course of experimental autoimmune encephalomyelitis
      and increased macrophage infiltration as well as proinflammatory gene expression
      in the spleen and spinal cord. Furthermore, Mas deficiency promoted
      atherosclerosis by affecting macrophage infiltration and migration and led to
      increased oxidative stress as well as impaired endothelial function in ApoE
      deficient mice. In summary, we identified the Mas axis as an important factor in
      macrophage function during inflammation of the central nervous and vascular
      system in vivo. Modulating the Mas axis may constitute an interesting therapeutic
      target in multiple sclerosis and/or atherosclerosis.

PMID- 27872281
TI  - Interactions of divalent cations with calcium binding sites of BK channels reveal
      independent motions within the gating ring.
AB  - Large-conductance voltage- and calcium-activated K+ (BK) channels are key
      physiological players in muscle, nerve, and endocrine function by integrating
      intracellular Ca2+ and membrane voltage signals. The open probability of BK
      channels is regulated by the intracellular concentration of divalent cations
      sensed by a large structure in the BK channel called the "gating ring," which is
      formed by four tandems of regulator of conductance for K+ (RCK1 and RCK2)
      domains. In contrast to Ca2+ that binds to both RCK domains, Mg2+, Cd2+, or Ba2+
      interact preferentially with either one or the other. Interaction of cations with
      their binding sites causes molecular rearrangements of the gating ring, but how
      these motions occur remains elusive. We have assessed the separate contributions
      of each RCK domain to the cation-induced gating-ring structural rearrangements,
      using patch-clamp fluorometry. Here we show that Mg2+ and Ba2+ selectively induce
      structural movement of the RCK2 domain, whereas Cd2+ causes motions of RCK1, in
      all cases substantially smaller than those elicited by Ca2+ By combining divalent
      species interacting with unique sites, we demonstrate that RCK1 and RCK2 domains
      move independently when their specific binding sites are occupied. Moreover,
      binding of chemically distinct cations to both RCK domains is additive, emulating
      the effect of fully occupied Ca2+ binding sites.

PMID- 27872283
TI  - Correction for Adel et al., Evolutionary alteration of ALOX15 specificity
      optimizes the biosynthesis of antiinflammatory and proresolving lipoxins.

PMID- 27872282
TI  - Correction to Supporting Information for Adel et al., Evolutionary alteration of
      ALOX15 specificity optimizes the biosynthesis of antiinflammatory and
      proresolving lipoxins.

PMID- 27872284
TI  - Disparities in influenza mortality and transmission related to sociodemographic
      factors within Chicago in the pandemic of 1918.
AB  - Social factors have been shown to create differential burden of influenza across
      different geographic areas. We explored the relationship between potential
      aggregate-level social determinants and mortality during the 1918 influenza
      pandemic in Chicago using a historical dataset of 7,971 influenza and pneumonia
      deaths. Census tract-level social factors, including rates of illiteracy,
      homeownership, population, and unemployment, were assessed as predictors of
      pandemic mortality in Chicago. Poisson models fit with generalized estimating
      equations (GEEs) were used to estimate the association between social factors and
      the risk of influenza and pneumonia mortality. The Poisson model showed that
      influenza and pneumonia mortality increased, on average, by 32.2% for every 10%
      increase in illiteracy rate adjusted for population density, homeownership,
      unemployment, and age. We also found a significant association between
      transmissibility and population density, illiteracy, and unemployment but not
      homeownership. Lastly, analysis of the point locations of reported influenza and
      pneumonia deaths revealed fine-scale spatiotemporal clustering. This study shows
      that living in census tracts with higher illiteracy rates increased the risk of
      influenza and pneumonia mortality during the 1918 influenza pandemic in Chicago.
      Our observation that disparities in structural determinants of neighborhood-level
      health lead to disparities in influenza incidence in this pandemic suggests that
      disparities and their determinants should remain targets of research and control
      in future pandemics.

PMID- 27872286
TI  - Linguistic positivity in historical texts reflects dynamic environmental and
      psychological factors.
AB  - People use more positive words than negative words. Referred to as "linguistic
      positivity bias" (LPB), this effect has been found across cultures and languages,
      prompting the conclusion that it is a panhuman tendency. However, although
      multiple competing explanations of LPB have been proposed, there is still no
      consensus on what mechanism(s) generate LPB or even on whether it is driven
      primarily by universal cognitive features or by environmental factors. In this
      work we propose that LPB has remained unresolved because previous research has
      neglected an essential dimension of language: time. In four studies conducted
      with two independent, time-stamped text corpora (Google books Ngrams and the New
      York Times), we found that LPB in American English has decreased during the last
      two centuries. We also observed dynamic fluctuations in LPB that were predicted
      by changes in objective environment, i.e., war and economic hardships, and by
      changes in national subjective happiness. In addition to providing evidence that
      LPB is a dynamic phenomenon, these results suggest that cognitive mechanisms
      alone cannot account for the observed dynamic fluctuations in LPB. At the least,
      LPB likely arises from multiple interacting mechanisms involving subjective,
      objective, and societal factors. In addition to having theoretical significance,
      our results demonstrate the value of newly available data sources in addressing
      long-standing scientific questions.

PMID- 27872285
TI  - Armed conflict and population displacement as drivers of the evolution and
      dispersal of Mycobacterium tuberculosis.
AB  - The "Beijing" Mycobacterium tuberculosis (Mtb) lineage 2 (L2) is spreading
      globally and has been associated with accelerated disease progression and
      increased antibiotic resistance. Here we performed a phylodynamic reconstruction
      of one of the L2 sublineages, the central Asian clade (CAC), which has recently
      spread to western Europe. We find that recent historical events have contributed
      to the evolution and dispersal of the CAC. Our timing estimates indicate that the
      clade was likely introduced to Afghanistan during the 1979-1989 Soviet-Afghan war
      and spread further after population displacement in the wake of the American
      invasion in 2001. We also find that drug resistance mutations accumulated on a
      massive scale in Mtb isolates from former Soviet republics after the fall of the
      Soviet Union, a pattern that was not observed in CAC isolates from Afghanistan.
      Our results underscore the detrimental effects of political instability and
      population displacement on tuberculosis control and demonstrate the power of
      phylodynamic methods in exploring bacterial evolution in space and time.

PMID- 27872287
TI  - Direct bulk-sensitive probe of 5f symmetry in URu2Si2.
AB  - The second-order phase transition into a hidden order phase in URu2Si2 goes along
      with an order parameter that is still a mystery, despite 30 years of research.
      However, it is understood that the symmetry of the order parameter must be
      related to the symmetry of the low-lying local electronic [Formula: see text]
      states. Here, we present results of a spectroscopic technique, namely core-level
      nonresonant inelastic X-ray scattering (NIXS). This method allows for the
      measurement of local high-multipole excitations and is bulk-sensitive. The
      observed anisotropy of the scattering function unambiguously shows that the
      5[Formula: see text] ground-state wave function is composed mainly of the
      [Formula: see text] with majority [Formula: see text] = [Formula: see text] +
      [Formula: see text] and/or [Formula: see text] singlet states. The incomplete
      dichroism indicates the possibility that quantum states of other irreducible
      representation are mixed into the ground state.

PMID- 27872288
TI  - MIF allele-dependent regulation of the MIF coreceptor CD44 and role in rheumatoid
      arthritis.
AB  - Fibroblast-like synoviocytes mediate joint destruction in rheumatoid arthritis
      and exhibit sustained proinflammatory and invasive properties. CD44 is a
      polymorphic transmembrane protein with defined roles in matrix interaction and
      tumor invasion that is also a signaling coreceptor for macrophage migration
      inhibitory factor (MIF), which engages cell surface CD74. High-expression MIF
      alleles (rs5844572) are associated with rheumatoid joint erosion, but whether MIF
      signaling through the CD74/CD44 receptor complex promotes upstream autoimmune
      responses or contributes directly to synovial joint destruction is unknown. We
      report here the functional regulation of CD44 by an autocrine pathway in synovial
      fibroblasts that is driven by high-expression MIF alleles to up-regulate an
      inflammatory and invasive phenotype. MIF increases CD44 expression, promotes its
      recruitment into a functional signal transduction complex, and stimulates
      alternative exon splicing, leading to expression of the CD44v3-v6 isoforms
      associated with oncogenic invasion. CD44 recruitment into the MIF receptor
      complex, downstream MAPK and RhoA signaling, and invasive phenotype require MIF
      and CD74 and are reduced by MIF pathway antagonists. These data support a
      functional role for high-MIF expression alleles and the two-component CD74/CD44
      MIF receptor in rheumatoid arthritis and suggest that pharmacologic inhibition of
      this pathway may offer a specific means to interfere with progressive joint
      destruction.

PMID- 27872290
TI  - The innate immune receptor Dectin-2 mediates the phagocytosis of cancer cells by
      Kupffer cells for the suppression of liver metastasis.
AB  - Tumor metastasis is the cause of most cancer deaths. Although metastases can form
      in multiple end organs, the liver is recognized as a highly permissive organ.
      Nevertheless, there is evidence for immune cell-mediated mechanisms that function
      to suppress liver metastasis by certain tumors, although the underlying
      mechanisms for the suppression of metastasis remain elusive. Here, we show that
      Dectin-2, a C-type lectin receptor (CLR) family of innate receptors, is critical
      for the suppression of liver metastasis of cancer cells. We provide evidence that
      Dectin-2 functions in resident macrophages in the liver, known as Kupffer cells,
      to mediate the uptake and clearance of cancer cells. Interestingly, Kupffer cells
      are selectively endowed with Dectin-2-dependent phagocytotic activity, with
      neither bone marrow-derived macrophages nor alveolar macrophages showing this
      potential. Concordantly, subcutaneous primary tumor growth and lung metastasis
      are not affected by the absence of Dectin-2. In addition, macrophage C-type
      lectin, a CLR known to be complex with Dectin-2, also contributes to the
      suppression of liver metastasis. Collectively, these results highlight the
      hitherto poorly understood mechanism of Kupffer cell-mediated control of
      metastasis that is mediated by the CLR innate receptor family, with implications
      for the development of anticancer therapy targeting CLRs.

PMID- 27872289
TI  - Fibrous nonlinear elasticity enables positive mechanical feedback between cells
      and ECMs.
AB  - In native states, animal cells of many types are supported by a fibrous network
      that forms the main structural component of the ECM. Mechanical interactions
      between cells and the 3D ECM critically regulate cell function, including growth
      and migration. However, the physical mechanism that governs the cell interaction
      with fibrous 3D ECM is still not known. In this article, we present single-cell
      traction force measurements using breast tumor cells embedded within 3D collagen
      matrices. We recreate the breast tumor mechanical environment by controlling the
      microstructure and density of type I collagen matrices. Our results reveal a
      positive mechanical feedback loop: cells pulling on collagen locally align and
      stiffen the matrix, and stiffer matrices, in return, promote greater cell force
      generation and a stiffer cell body. Furthermore, cell force transmission distance
      increases with the degree of strain-induced fiber alignment and stiffening of the
      collagen matrices. These findings highlight the importance of the nonlinear
      elasticity of fibrous matrices in regulating cell-ECM interactions within a 3D
      context, and the cell force regulation principle that we uncover may contribute
      to the rapid mechanical tissue stiffening occurring in many diseases, including
      cancer and fibrosis.

PMID- 27872291
TI  - Molecular evidence of keratin and melanosomes in feathers of the Early Cretaceous
      bird Eoconfuciusornis.
AB  - Microbodies associated with feathers of both nonavian dinosaurs and early birds
      were first identified as bacteria but have been reinterpreted as melanosomes.
      Whereas melanosomes in modern feathers are always surrounded by and embedded in
      keratin, melanosomes embedded in keratin in fossils has not been demonstrated.
      Here we provide multiple independent molecular analyses of both microbodies and
      the associated matrix recovered from feathers of a new specimen of the basal bird
      Eoconfuciusornis from the Early Cretaceous Jehol Biota of China. Our work
      represents the oldest ultrastructural and immunological recognition of avian beta
      keratin from an Early Cretaceous (~130-Ma) bird. We apply immunogold to identify
      protein epitopes at high resolution, by localizing antibody-antigen complexes to
      specific fossil ultrastructures. Retention of original keratinous proteins in the
      matrix surrounding electron-opaque microbodies supports their assignment as
      melanosomes and adds to the criteria employable to distinguish melanosomes from
      microbial bodies. Our work sheds new light on molecular preservation within
      normally labile tissues preserved in fossils.

PMID- 27872292
TI  - Disturbance is the key to plant invasions in cold environments.
AB  - Until now, nonnative plant species were rarely found at high elevations and
      latitudes. However, partly because of climate warming, biological invasions are
      now on the rise in these extremely cold environments. These plant invasions make
      it timely to undertake a thorough experimental assessment of what has previously
      been holding them back. This knowledge is key to developing efficient management
      of the increasing risks of cold-climate invasions. Here, we integrate human
      interventions (i.e., disturbance, nutrient addition, and propagule input) and
      climatic factors (i.e., temperature) into one seed-addition experiment across two
      continents: the subantarctic Andes and subarctic Scandinavian mountains
      (Scandes), to disentangle their roles in limiting or favoring plant invasions.
      Disturbance was found as the main determinant of plant invader success (i.e.,
      establishment, growth, and flowering) along the entire cold-climate gradient,
      explaining 40-60% of the total variance in our models, with no indication of any
      facilitative effect from the native vegetation. Higher nutrient levels
      additionally stimulated biomass production and flowering. Establishment and
      flowering displayed a hump-shaped response with increasing elevation, suggesting
      that competition is the main limit on invader success at low elevations, as
      opposed to low-growing-season temperatures at high elevations. Our experiment
      showed, however, that nonnative plants can establish, grow, and flower well above
      their current elevational limits in high-latitude mountains. We thus argue that
      cold-climate ecosystems are likely to see rapid increases in plant invasions in
      the near future as a result of a synergistic interaction between increasing human
      mediated disturbances and climate warming.

PMID- 27872293
TI  - Emergence of an abstract categorical code enabling the discrimination of
      temporally structured tactile stimuli.
AB  - The problem of neural coding in perceptual decision making revolves around two
      fundamental questions: (i) How are the neural representations of sensory stimuli
      related to perception, and (ii) what attributes of these neural responses are
      relevant for downstream networks, and how do they influence decision making? We
      studied these two questions by recording neurons in primary somatosensory (S1)
      and dorsal premotor (DPC) cortex while trained monkeys reported whether the
      temporal pattern structure of two sequential vibrotactile stimuli (of equal mean
      frequency) was the same or different. We found that S1 neurons coded the temporal
      patterns in a literal way and only during the stimulation periods and did not
      reflect the monkeys' decisions. In contrast, DPC neurons coded the stimulus
      patterns as broader categories and signaled them during the working memory,
      comparison, and decision periods. These results show that the initial sensory
      representation is transformed into an intermediate, more abstract categorical
      code that combines past and present information to ultimately generate a
      perceptually informed choice.

PMID- 27872294
TI  - US daily temperature records past, present, and future.
AB  - Observed temperature extremes over the continental United States can be
      represented by the ratio of daily record high temperatures to daily record low
      minimum temperatures, and this ratio has increased to a value of about 2 to 1,
      averaged over the first decade of the 21st century, albeit with large interannual
      variability. Two different versions of a global coupled climate model (CCSM4), as
      well as 23 other coupled model intercomparison project phase 5 (CMIP5) models,
      show larger values of this ratio than observations, mainly as a result of greater
      numbers of record highs since the 1980s compared with observations. This is
      partly because of the "warm 1930s" in the observations, which made it more
      difficult to set record highs later in the century, and partly because of a trend
      toward less rainfall and reduced evapotranspiration in the model versions
      compared with observations. We compute future projections of this ratio on the
      basis of its estimated dependence on mean temperature increase, which we find
      robustly at play in both observations and simulations. The use of this relation
      also has the advantage of removing dependence of a projection on a specific
      scenario. An empirical projection of the ratio of record highs to record lows is
      obtained from the nonlinear relationship in observations from 1930 to 2015, thus
      correcting downward the likely biased future projections of the model. For
      example, for a 3  degrees C warming in US temperatures, the ratio of record highs
      to lows is projected to be ~15 +/- 8 compared to the present average ratio of
      just over 2.

PMID- 27872295
TI  - Characterization of the heterooligomeric red-type rubisco activase from red
      algae.
AB  - The photosynthetic CO2-fixing enzyme ribulose 1,5-bisphosphate
      carboxylase/oxygenase (rubisco) is inhibited by nonproductive binding of its
      substrate ribulose-1,5-bisphosphate (RuBP) and other sugar phosphates.
      Reactivation requires ATP-hydrolysis-powered remodeling of the inhibited
      complexes by diverse molecular chaperones known as rubisco activases (Rcas).
      Eukaryotic phytoplankton of the red plastid lineage contain so-called red-type
      rubiscos, some of which have been shown to possess superior kinetic properties to
      green-type rubiscos found in higher plants. These organisms are known to encode
      multiple homologs of CbbX, the alpha-proteobacterial red-type activase. Here we
      show that the gene products of two cbbX genes encoded by the nuclear and plastid
      genomes of the red algae Cyanidioschyzon merolae are nonfunctional in isolation,
      but together form a thermostable heterooligomeric Rca that can use both alpha
      proteobacterial and red algal-inhibited rubisco complexes as a substrate. The
      mechanism of rubisco activation appears conserved between the bacterial and the
      algal systems and involves threading of the rubisco large subunit C terminus.
      Whereas binding of the allosteric regulator RuBP induces oligomeric transitions
      to the bacterial activase, it merely enhances the kinetics of ATP hydrolysis in
      the algal enzyme. Mutational analysis of nuclear and plastid isoforms
      demonstrates strong coordination between the subunits and implicates the nuclear
      encoded subunit as being functionally dominant. The plastid-encoded subunit may
      be catalytically inert. Efforts to enhance crop photosynthesis by transplanting
      red algal rubiscos with enhanced kinetics will need to take into account the
      requirement for a compatible Rca.

PMID- 27872296
TI  - Mechanism of gating by calcium in connexin hemichannels.
AB  - Aberrant opening of nonjunctional connexin hemichannels at the plasma membrane is
      associated with many diseases, including ischemia and muscular dystrophy. Proper
      control of hemichannel opening is essential to maintain cell viability and is
      achieved by physiological levels of extracellular Ca2+, which drastically reduce
      hemichannel activity. Here we examined the role of conserved charged residues
      that form electrostatic networks near the extracellular entrance of the connexin
      pore, a region thought to be involved in gating rearrangements of hemichannels.
      Molecular dynamics simulations indicate discrete sites for Ca2+ interaction and
      consequent disruption of salt bridges in the open hemichannels. Experimentally,
      we found that disruption of these salt bridges by mutations facilitates
      hemichannel closing. Two negatively charged residues in these networks are
      putative Ca2+ binding sites, forming a Ca2+-gating ring near the extracellular
      entrance of the pore. Accessibility studies showed that this Ca2+-bound gating
      ring does not prevent access of ions or small molecules to positions deeper into
      the pore, indicating that the physical gate is below the Ca2+-gating ring. We
      conclude that intra- and intersubunit electrostatic networks at the extracellular
      entrance of the hemichannel pore play critical roles in hemichannel gating
      reactions and are tightly controlled by extracellular Ca2+ Our findings provide a
      general mechanism for Ca2+ gating among different connexin hemichannel isoforms.

PMID- 27872298
TI  - Correction for Zhang et al., Chilling-induced tomato flavor loss is associated
      with altered volatile synthesis and transient changes in DNA methylation.

PMID- 27872297
TI  - Singular role for T-BET+CXCR3+ regulatory T cells in protection from autoimmune
      diabetes.
AB  - Foxp3+ regulatory T (Treg) cells are crucial for restraining inflammation in a
      variety of autoimmune diseases, including type 1 diabetes (T1D). However, the
      transcriptional and functional phenotypes of Treg cells within the pancreatic
      lesion remain poorly understood. Here we characterized pancreas-infiltrating Treg
      cells in the NOD mouse model of T1D and uncovered a substantial enrichment of the
      Treg subpopulation expressing the chemokine receptor CXCR3. Accumulation of
      CXCR3+ Treg cells within pancreatic islets was dependent on the transcription
      factor T-BET, and genetic ablation of T-BET increased the onset and penetrance of
      disease, abrogating the sex bias normally seen in the NOD model. Both male and
      female mice lacking T-BET+ Treg cells showed a more aggressive insulitic
      infiltrate, reflected most prominently by elevated production of type 1
      cytokines. Our results suggest the possibility of fine therapeutic targeting of
      Treg cells, in a tissue- and cell-subset-specific fashion, as a more focused
      immunotherapy for T1D.

PMID- 27872301
TI  - Baby birds do not always tell the truth.

PMID- 27872300
TI  - Estimating enhanced prevaccination measles transmission hotspots in the context
      of cross-scale dynamics.
AB  - A key question in clarifying human-environment interactions is how dynamic
      complexity develops across integrative scales from molecular to population and
      global levels. Apart from its public health importance, measles is an excellent
      test bed for such an analysis. Simple mechanistic models have successfully
      illuminated measles dynamics at the city and country levels, revealing seasonal
      forcing of transmission as a major driver of long-term epidemic behavior.
      Seasonal forcing ties closely to patterns of school aggregation at the individual
      and community levels, but there are few explicit estimates of school transmission
      due to the relative lack of epidemic data at this scale. Here, we use data from a
      1904 measles outbreak in schools in Woolwich, London, coupled with a stochastic
      Susceptible-Infected-Recovered model to analyze measles incidence data. Our
      results indicate that transmission within schools and age classes is higher than
      previous population-level serological data would suggest. This analysis sheds
      quantitative light on the role of school-aged children in measles cross-scale
      dynamics, as we illustrate with references to the contemporary vaccination
      landscape.

PMID- 27872299
TI  - The emergence of longevous populations.
AB  - The human lifespan has traversed a long evolutionary and historical path, from
      short-lived primate ancestors to contemporary Japan, Sweden, and other longevity
      frontrunners. Analyzing this trajectory is crucial for understanding biological
      and sociocultural processes that determine the span of life. Here we reveal a
      fundamental regularity. Two straight lines describe the joint rise of life
      expectancy and lifespan equality: one for primates and the second one over the
      full range of human experience from average lifespans as low as 2 y during
      mortality crises to more than 87 y for Japanese women today. Across the primate
      order and across human populations, the lives of females tend to be longer and
      less variable than the lives of males, suggesting deep evolutionary roots to the
      male disadvantage. Our findings cast fresh light on primate evolution and human
      history, opening directions for research on inequality, sociality, and aging.

PMID- 27872303
TI  - Homogeneous nucleation: Patching the way from the macroscopic to the nanoscopic
      description.

PMID- 27872302
TI  - Long-term aggregation of larval fish siblings during dispersal along an open
      coast.
AB  - Pelagic dispersal of most benthic marine organisms is a fundamental driver of
      population distribution and persistence and is thought to lead to highly mixed
      populations. However, the mechanisms driving dispersal pathways of larvae along
      open coastlines are largely unknown. To examine the degree to which early stages
      can remain spatially coherent during dispersal, we measured genetic relatedness
      within a large pulse of newly recruited splitnose rockfish (Sebastes diploproa),
      a live-bearing fish whose offspring settle along the US Pacific Northwest coast
      after spending up to a year in the pelagic environment. A total of 11.6% of the
      recruits in a single recruitment pulse were siblings, providing the first
      evidence for persistent aggregation throughout a long dispersal period. Such
      protracted aggregation has profound implications for our understanding of larval
      dispersal, population connectivity, and gene flow within demersal marine
      populations.

PMID- 27872304
TI  - Evidence of isotopic fractionation of natural uranium in cultured human cells.
AB  - The study of the isotopic fractionation of endogen elements and toxic heavy
      metals in living organisms for biomedical applications, and for metabolic and
      toxicological studies, is a cutting-edge research topic. This paper shows that
      human neuroblastoma cells incorporated small amounts of uranium (U) after
      exposure to 10 uM natural U, with preferential uptake of the 235U isotope with
      regard to 238U. Efforts were made to develop and then validate a procedure for
      highly accurate n(238U)/n(235U) determinations in microsamples of cells. We found
      that intracellular U is enriched in 235U by 0.38 +/- 0.130/00 (2sigma, n = 7)
      relative to the exposure solutions. These in vitro experiments provide clues for
      the identification of biological processes responsible for uranium isotopic
      fractionation and link them to potential U incorporation pathways into neuronal
      cells. Suggested incorporation processes are a kinetically controlled process,
      such as facilitated transmembrane diffusion, and the uptake through a high
      affinity uranium transport protein involving the modification of the uranyl
      (UO22+) coordination sphere. These findings open perspectives on the use of
      isotopic fractionation of metals in cellular models, offering a probe to track
      uptake/transport pathways and to help decipher associated cellular metabolic
      processes.

PMID- 27872305
TI  - Multistep crystallization processes: How not to make perfect single crystals.

PMID- 27872307
TI  - High-pressure phase of brucite stable at Earth's mantle transition zone and lower
      mantle conditions.
AB  - We investigate the high-pressure phase diagram of the hydrous mineral brucite,
      Mg(OH)2, using structure search algorithms and ab initio simulations. We predict
      a high-pressure phase stable at pressure and temperature conditions found in cold
      subducting slabs in Earth's mantle transition zone and lower mantle. This
      prediction implies that brucite can play a much more important role in water
      transport and storage in Earth's interior than hitherto thought. The predicted
      high-pressure phase, stable in calculations between 20 and 35 GPa and up to 800
      K, features MgO6 octahedral units arranged in the anatase-TiO2 structure. Our
      findings suggest that brucite will transform from a layered to a compact 3D
      network structure before eventual decomposition into periclase and ice. We show
      that the high-pressure phase has unique spectroscopic fingerprints that should
      allow for straightforward detection in experiments. The phase also has distinct
      elastic properties that might make its direct detection in the deep Earth
      possible with geophysical methods.

PMID- 27872306
TI  - Paired quantitative and qualitative assessment of the replication-competent HIV-1
      reservoir and comparison with integrated proviral DNA.
AB  - HIV-1-infected individuals harbor a latent reservoir of infected CD4+ T cells
      that is not eradicated by antiretroviral therapy (ART). This reservoir presents
      the greatest barrier to an HIV-1 cure and has remained difficult to characterize,
      in part, because the vast majority of integrated sequences are defective and
      incapable of reactivation. To characterize the replication-competent reservoir,
      we have combined two techniques, quantitative viral outgrowth and qualitative
      sequence analysis of clonal outgrowth viruses. Leukapheresis samples from four
      fully ART-suppressed, chronically infected individuals were assayed at two time
      points separated by a 4- to 6-mo interval. Overall, 54% of the viruses emerging
      from the latent reservoir showed gp160 env sequences that were identical to at
      least one other virus. Moreover, 43% of the env sequences from viruses emerging
      from the reservoir were part of identical groups at the two time points. Groups
      of identical expanded sequences made up 54% of proviral DNA, and, as might be
      expected, the sequences of replication-competent viruses in the active reservoir
      showed limited overlap with integrated proviral DNA, most of which is known to
      represent defective viruses. Finally, there was an inverse correlation between
      proviral DNA clone size and the probability of reactivation, suggesting that
      replication-competent viruses are less likely to be found among highly expanded
      provirus-containing cell clones.

PMID- 27872308
TI  - Atomistic insight into lipid translocation by a TMEM16 scramblase.
AB  - The transmembrane protein 16 (TMEM16) family of membrane proteins includes both
      lipid scramblases and ion channels involved in olfaction, nociception, and blood
      coagulation. The crystal structure of the fungal Nectria haematococca TMEM16
      (nhTMEM16) scramblase suggested a putative mechanism of lipid transport, whereby
      polar and charged lipid headgroups move through the low-dielectric environment of
      the membrane by traversing a hydrophilic groove on the membrane-spanning surface
      of the protein. Here, we use computational methods to explore the membrane
      protein interactions involved in lipid scrambling. Fast, continuum membrane
      bending calculations reveal a global pattern of charged and hydrophobic surface
      residues that bends the membrane in a large-amplitude sinusoidal wave, resulting
      in bilayer thinning across the hydrophilic groove. Atomic simulations uncover two
      lipid headgroup-interaction sites flanking the groove. The cytoplasmic site
      nucleates headgroup-dipole stacking interactions that form a chain of lipid
      molecules that penetrate into the groove. In two instances, a cytoplasmic lipid
      interdigitates into this chain, crosses the bilayer, and enters the extracellular
      leaflet, and the reverse process happens twice as well. Continuum membrane
      bending analysis carried out on homology models of mammalian homologs shows that
      these family members also bend the membrane-even those that lack scramblase
      activity. Sequence alignments show that the lipid-interaction sites are conserved
      in many family members but less so in those with reduced scrambling ability. Our
      analysis provides insight into how large-scale membrane bending and protein
      chemistry facilitate lipid permeation in the TMEM16 family, and we hypothesize
      that membrane interactions also affect ion permeation.

PMID- 27872309
TI  - Phosphate-binding pocket in Dicer-2 PAZ domain for high-fidelity siRNA
      production.
AB  - The enzyme Dicer produces small silencing RNAs such as micro-RNAs (miRNAs) and
      small interfering RNAs (siRNAs). In Drosophila, Dicer-1 produces ~22-24-nt miRNAs
      from pre-miRNAs, whereas Dicer-2 makes 21-nt siRNAs from long double-stranded
      RNAs (dsRNAs). How Dicer-2 precisely makes 21-nt siRNAs with a remarkably high
      fidelity is unknown. Here we report that recognition of the 5'-monophosphate of a
      long dsRNA substrate by a phosphate-binding pocket in the Dicer-2 PAZ (Piwi,
      Argonaute, and Zwille/Pinhead) domain is crucial for the length fidelity, but not
      the efficiency, in 21-nt siRNA production. Loss of the length fidelity, meaning
      increased length heterogeneity of siRNAs, caused by point mutations in the
      phosphate-binding pocket of the Dicer-2 PAZ domain decreased RNA silencing
      activity in vivo, showing the importance of the high fidelity to make 21-nt
      siRNAs. We propose that the 5'-monophosphate of a long dsRNA substrate is
      anchored by the phosphate-binding pocket in the Dicer-2 PAZ domain and the
      distance between the pocket and the RNA cleavage active site in the RNaseIII
      domain corresponds to the 21-nt pitch in the A-form duplex of a long dsRNA
      substrate, resulting in high-fidelity 21-nt siRNA production. This study sheds
      light on the molecular mechanism by which Dicer-2 produces 21-nt siRNAs with a
      remarkably high fidelity for efficient RNA silencing.

PMID- 27872310
TI  - Efficient replacement of plasma membrane outer leaflet phospholipids and
      sphingolipids in cells with exogenous lipids.
AB  - Our understanding of membranes and membrane lipid function has lagged far behind
      that of nucleic acids and proteins, largely because it is difficult to manipulate
      cellular membrane lipid composition. To help solve this problem, we show that
      methyl-alpha-cyclodextrin (MalphaCD)-catalyzed lipid exchange can be used to
      maximally replace the sphingolipids and phospholipids in the outer leaflet of the
      plasma membrane of living mammalian cells with exogenous lipids, including
      unnatural lipids. In addition, lipid exchange experiments revealed that 70-80% of
      cell sphingomyelin resided in the plasma membrane outer leaflet; the asymmetry of
      metabolically active cells was similar to that previously defined for
      erythrocytes, as judged by outer leaflet lipid composition; and plasma membrane
      outer leaflet phosphatidylcholine had a significantly lower level of unsaturation
      than phosphatidylcholine in the remainder of the cell. The data also provided a
      rough estimate for the total cellular lipids residing in the plasma membrane
      (about half). In addition to such lipidomics applications, the exchange method
      should have wide potential for investigations of lipid function and modification
      of cellular behavior by modification of lipids.

PMID- 27872311
TI  - Methyltransferase-like protein 16 binds the 3'-terminal triple helix of MALAT1
      long noncoding RNA.
AB  - Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a cancer
      promoting long noncoding RNA, accumulates in cells by using a 3'-triple-helical
      RNA stability element for nuclear expression (ENE). The ENE, a stem-loop
      structure containing a U-rich internal loop, interacts with a downstream A-rich
      tract (ENE+A) to form a blunt-ended triple helix composed of nine U*A-U triples
      interrupted by a C*G-C triple and C-G doublet. This unique structure prompted us
      to explore the possibility of protein binding. Native gel-shift assays revealed a
      shift in radiolabeled MALAT1 ENE+A RNA upon addition of HEK293T cell lysate.
      Competitive gel-shift assays suggested that protein binding depends not only on
      the triple-helical structure but also its nucleotide composition. Selection from
      the lysate using a biotinylated-RNA probe followed by mass spectrometry
      identified methyltransferase-like protein 16 (METTL16), a putative RNA
      methyltransferase, as an interacting protein of the MALAT1 ENE+A. Gel-shift
      assays confirmed the METTL16-MALAT1 ENE+A interaction in vitro: Binding was
      observed with recombinant METTL16, but diminished in lysate depleted of METTL16,
      and a supershift was detected after adding anti-METTL16 antibody. Importantly,
      RNA immunoprecipitation after in vivo UV cross-linking and an in situ proximity
      ligation assay for RNA-protein interactions confirmed an association between
      METTL16 and MALAT1 in cells. METTL16 is an abundant (~5 * 105 molecules per cell)
      nuclear protein in HeLa cells. Its identification as a triple-stranded RNA
      binding protein supports the formation of RNA triple helices inside cells and
      suggests the existence of a class of triple-stranded RNA binding proteins, which
      may enable the discovery of additional cellular RNA triple helices.

PMID- 27872312
TI  - Exon skipping of FcepsilonRIbeta eliminates expression of the high-affinity IgE
      receptor in mast cells with therapeutic potential for allergy.
AB  - Allergic diseases are driven by activation of mast cells and release of mediators
      in response to IgE-directed antigens. However, there are no drugs currently
      available that can specifically down-regulate mast cell function in vivo when
      chronically administered. Here, we describe an innovative approach for targeting
      mast cells in vitro and in vivo using antisense oligonucleotide-mediated exon
      skipping of the beta-subunit of the high-affinity IgE receptor (FcepsilonRIbeta)
      to eliminate surface high-affinity IgE receptor (FcepsilonRI) expression and
      function, rendering mast cells unresponsive to IgE-mediated activation. As
      FcepsilonRIbeta expression is restricted to mast cells and basophils, this
      approach would selectively target these cell types. Given the success of exon
      skipping in clinical trials to treat genetic diseases such as Duchenne muscular
      dystrophy, we propose that exon skipping of FcepsilonRIbeta is a potential
      approach for mast cell-specific treatment of allergic diseases.

PMID- 27872313
TI  - The earliest maize from San Marcos Tehuacan is a partial domesticate with genomic
      evidence of inbreeding.
AB  - Pioneering archaeological expeditions lead by Richard MacNeish in the 1960s
      identified the valley of Tehuacan as an important center of early Mesoamerican
      agriculture, providing by far the widest collection of ancient crop remains,
      including maize. In 2012, a new exploration of San Marcos cave (Tehuacan, Mexico)
      yielded nonmanipulated maize specimens dating at a similar age of 5,300-4,970
      calibrated y B.P. On the basis of shotgun sequencing and genomic comparisons to
      Balsas teosinte and modern maize, we show herein that the earliest maize from San
      Marcos cave was a partial domesticate diverging from the landraces and containing
      ancestral allelic variants that are absent from extant maize populations. Whereas
      some domestication loci, such as teosinte branched1 (tb1) and brittle endosperm2
      (bt2), had already lost most of the nucleotide variability present in Balsas
      teosinte, others, such as teosinte glume architecture1 (tga1) and sugary1 (su1),
      conserved partial levels of nucleotide variability that are absent from extant
      maize. Genetic comparisons among three temporally convergent samples revealed
      that they were homozygous and identical by descent across their genome. Our
      results indicate that the earliest maize from San Marcos was already inbred,
      opening the possibility for Tehuacan maize cultivation evolving from reduced
      founder populations of isolated and perhaps self-pollinated individuals.

PMID- 27872314
TI  - Molecular basis for the broad substrate selectivity of a peptide
      prenyltransferase.
AB  - The cyanobactin prenyltransferases catalyze a series of known or unprecedented
      reactions on millions of different substrates, with no easily observable
      recognition motif and exquisite regioselectivity. Here we define the basis of
      broad substrate tolerance for the otherwise uncharacterized TruF family. We
      determined the structures of the Tyr-prenylating enzyme PagF, in complex with an
      isoprenoid donor analog and a panel of linear and macrocyclic peptide substrates.
      Unexpectedly, the structures reveal a truncated barrel fold, wherein binding of
      large peptide substrates is necessary to complete a solvent-exposed hydrophobic
      pocket to form the catalytically competent active site. Kinetic, mutational,
      chemical, and computational analyses revealed the structural basis of
      selectivity, showing a small motif within peptide substrates that is sufficient
      for recognition by the enzyme. Attaching this 2-residue motif to two random
      peptides results in their isoprenylation by PagF, demonstrating utility as a
      general biocatalytic platform for modifications on any peptide substrate.

PMID- 27872316
TI  - Outcomes of Acute Myocardial Infarction Patients Implanted With Biodegradable
      Polymer Biolimus-Eluting Stents Versus New-Generation Durable Polymer Drug
      Eluting Stents: A Retrospective Analysis.
AB  - We compared outcomes between biodegradable polymer biolimus-eluting stent (BP
      BES) and new-generation durable polymer drug-eluting stent (DP-DES) implantations
      in patients with acute myocardial infarction (MI). Among 13472 patients with
      acute MI in a nationwide registry, 557 (64.8%) were in the BP-BES and 303 (35.2%)
      in the new-generation DP-DES group following coronary reperfusion. The occurrence
      of major adverse cardiac events (MACE; death, MI, revascularization) and stent
      thrombosis was compared. Major adverse cardiac events occurred in 53 (6.2%)
      patients and showed similar rates between the BP-BES and new-generation DP-DES
      groups (all: 6.6% vs 5.9%, P = .652; propensity score [PS] matched: n = 380, 6.3%
      vs 5.3%, P = .623). Stent thrombosis did not differ between groups (all: 0.3% vs
      0.4%, P = .892; PS matched: 0.5% vs 0.5%, P = 1.000). Major adverse cardiac event
      free survival was comparable between groups (all: 93.4% vs 94.1%, log-rank P =
      .357; PS matched: 93.7% vs 94.7%, log-rank P = .445). Biodegradable polymer
      biolimus-eluting stent was not associated with MACE (all: hazard ratio [HR],
      1.67; 95% confidence interval [CI], 0.75-3.74; P = 0.212; PS matched: HR, 1.05;
      95% CI, 0.40-2.75; P = .915). In conclusion, in patients with acute MI, BP-BES
      was equivalent to the new-generation DP-DES in terms of outcomes.

PMID- 27872315
TI  - Large numbers of vertebrates began rapid population decline in the late 19th
      century.
AB  - Accelerated losses of biodiversity are a hallmark of the current era. Large
      declines of population size have been widely observed and currently 22,176
      species are threatened by extinction. The time at which a threatened species
      began rapid population decline (RPD) and the rate of RPD provide important clues
      about the driving forces of population decline and anticipated extinction time.
      However, these parameters remain unknown for the vast majority of threatened
      species. Here we analyzed the genetic diversity data of nuclear and mitochondrial
      loci of 2,764 vertebrate species and found that the mean genetic diversity is
      lower in threatened species than in related nonthreatened species. Our
      coalescence-based modeling suggests that in many threatened species the RPD began
      ~123 y ago (a 95% confidence interval of 20-260 y). This estimated date coincides
      with widespread industrialization and a profound change in global living
      ecosystems over the past two centuries. On average the population size declined
      by ~25% every 10 y in a threatened species, and the population size was reduced
      to ~5% of its ancestral size. Moreover, the ancestral size of threatened species
      was, on average, ~22% smaller than that of nonthreatened species. Because the
      time period of RPD is short, the cumulative effect of RPD on genetic diversity is
      still not strong, so that the smaller ancestral size of threatened species may be
      the major cause of their reduced genetic diversity; RPD explains 24.1-37.5% of
      the difference in genetic diversity between threatened and nonthreatened species.

PMID- 27872317
TI  - First-in-Human Experience With the Gore Balloon-Expandable Covered Endoprosthesis
      in Iliac Artery Occlusive Disease.
AB  - PURPOSE: To report the first-in-human iliac artery experience of a new balloon
      expandable covered endoprosthesis. METHODS: A prospective, single-center pilot
      study recruited 30 symptomatic patients (mean age 64 years; 18 men) to evaluate
      the safety and early efficacy of the new Gore balloon-expandable covered
      endoprosthesis for the treatment of de novo or restenotic common and/or external
      iliac artery lesions. According to protocol, up to 2 discrete lesions could be
      treated with a maximum total treated length <=110 mm. Follow-up included clinical
      evaluation with duplex ultrasound at 1, 6, and 12 months. Data are presented
      through 12-month follow-up. The primary safety endpoint was a composite of device
      or procedure-related death, myocardial infarction, or amputation in the treated
      leg within 30 days of the index procedure. Multiple performance outcomes were
      also evaluated. RESULTS: The primary 30-day safety endpoint was 0%. Per-subject
      estimates of primary patency, freedom from target lesion revascularization, and
      freedom from target vessel revascularization were 100% at 1 and 6 months and
      96.6% at 12 months. Estimates of assisted primary and secondary patency were both
      100% at 12 months. Freedom from major adverse events at 12 months was 100%. Most
      patients experienced improvements in Rutherford category, ankle-brachial index,
      and functional status that were sustained to 12 months. CONCLUSION: This positive
      first-in-human experience with the Gore balloon-expandable covered endoprosthesis
      suggests this device will have an important role in the management of aortoiliac
      occlusive disease.

PMID- 27872318
TI  - Biomechanical Indices for Rupture Risk Estimation in Abdominal Aortic Aneurysms.
AB  - PURPOSE: To review the use of biomechanical indices for the estimation of
      abdominal aortic aneurysm (AAA) rupture risk, emphasizing their potential use in
      a clinical setting. METHODS: A search of the PubMed, Embase, Scopus, and
      Compendex databases was made up to June 2015 to identify articles involving
      biomechanical analysis of AAA rupture risk. Outcome variables [aneurysm diameter,
      peak wall stress (PWS), peak wall shear stress (PWSS), wall strain, peak wall
      rupture index (PWRI), and wall stiffness] were compared for asymptomatic intact
      AAAs vs symptomatic or ruptured AAAs. For quantitative analysis of the pooled
      data, a random effects model was used to calculate the standard mean differences
      (SMDs) with the 95% confidence interval (CI) for the biomechanical indices.
      RESULTS: The initial database searches yielded 1894 independent articles of which
      19 were included in the analysis. The PWS was significantly higher in the
      symptomatic/ruptured group, with a SMD of 1.11 (95% CI 0.93 to 1.26, p<0.001).
      Likewise, the PWRI was significantly higher in the ruptured or symptomatic group,
      with a SMD of 1.15 (95% CI 0.30 to 2.01, p=0.008). After adjustment for the
      aneurysm diameter, the PWS remained higher in the ruptured or symptomatic group,
      with a SMD of 0.85 (95% CI 0.46 to 1.23, p<0.001). Less is known of the wall
      shear stress and wall strain indices, as too few studies were available for
      analysis. CONCLUSION: Biomechanical indices are a promising tool in the
      assessment of AAA rupture risk as they incorporate several factors, including
      geometry, tissue properties, and patient-specific risk factors. However, clinical
      implementation of biomechanical AAA assessment remains a challenge owing to a
      lack of standardization.

PMID- 27872319
TI  - Classification of Chimney EVAR-Related Endoleaks: Insights From the PERICLES
      Registry.

PMID- 27872320
TI  - Pott's disease: a major issue for an unaccompanied refugee minor.
AB  - The incidence of TB in children in Germany has been on a rise since 2008,
      especially among foreign-born individuals. With rapidly increasing numbers of
      refugees from the numerous areas of conflict, this increase in incidence is not
      expected to halt, neither in Germany nor in Europe in general. We report a case
      of insufficient tracking in a 16-year-old unaccompanied refugee minor from
      Somalia who had a positive interferon gamma release assay on arrival in Germany.
      No actions were undertaken, until 6 months later, an X-ray showed prominent hilar
      enlargement. Nine  months later, the patient presented to our hospital with
      abdominal pain, vomiting and B symptoms. Workup revealed a paravertebral abscess
      due to Pott's disease, a skeletal manifestation of Mycobacterium tuberculosis
      disease. The patient made a full recovery after a combination therapy for a total
      of 9 months.

PMID- 27872321
TI  - MSM in Bogota are living with HIV for extended periods without diagnosis or
      treatment.
AB  - We examined recency of infection in serum samples obtained from 69 newly
      identified HIV-positive cases in a sample of 1000 men who have sex with men (MSM)
      in Bogota. HIV antibody avidity assays were performed using the Architect HIV
      Ag/AB combo. Avidity indices ranged from 0.62 to 1.22, with a cut-off score below
      0.80 indicative of recent infection. Two samples were classified as recent, six
      fell within the gray zone (0.75 to 0.85), and the remaining 61 were considered
      established infections. Results provided evidence of widespread, long-term,
      undiagnosed HIV infection, as well as an estimate of one-year incidence at .25 in
      the population of MSM in Bogota. This incidence rate is approximately 8.5 times
      the rate estimated for the general adult population in Colombia. The large
      proportion of newly diagnosed cases found among individuals with established
      infections indicates that many MSM in Bogota are living with HIV for extended
      periods without being diagnosed and treated. Greater efforts to detect and treat
      undiagnosed infections are crucial to decrease HIV incidence and increase maximum
      effectiveness of medical intervention. Given the over-representation of MSM and
      transgender women in the HIV epidemic in Colombia, such efforts should
      specifically target this population.

PMID- 27872322
TI  - HIV care and treatment of American Indians/Alaska natives with diagnosed HIV
      infection - 27 states and the District of Columbia, 2012.
AB  - The objective of this study was to measure linkage to care, retention in care,
      and suppressed viral load (VL) among American Indians/Alaska Natives (AIs/ANs)
      aged >=13 years with diagnosed HIV infection. We used national HIV case
      surveillance data to measure linkage to care, defined as >=1 CD4 or VL test <=1
      month after HIV diagnosis during 2013; retention in care, defined as >=2 CD4 or
      VL tests >=3 months apart during 2012; and suppressed VL, defined as <200
      copies/mL at the most recent VL test during 2012. In 2013, 74.1% of AIs/ANs were
      linked to care. At year-end 2012, 46.9% of AIs/ANs were retained in care and
      45.1% were virally suppressed. A lower percentage of females (41.3%), compared
      with males (46.5), were virally suppressed. By age group, the lowest percentage
      of virally suppressed AIs/ANs (37.5%) were aged 13-34 years. To improve
      individual health and to prevent HIV among AIs/ANs, outcomes must improve -
      particularly for female AIs/ANs and for AIs/ANs aged 13-34 years. Screening for
      HIV infection in accordance with Centers for Disease Control and Prevention's
      testing recommendations can lead to improvements along the continuum of HIV care.

PMID- 27872323
TI  - Rates of sexual history taking and screening in HIV-positive men who have sex
      with men.
AB  - A case note audit was undertaken of HIV-positive men who have sex with men (MSM)
      to ascertain whether national guidelines for taking sexual histories, including
      recreational drug use and sexually transmitted infection (STI) screening were
      being met. The notes of 142 HIV-positive men seen in 2015 were available, of whom
      85 were MSM. Information was collected regarding sexual history, recreational
      drug use documentation, sexually transmitted infection screen offer and test
      results. Seventy-seven (91%) of the MSM had a sexual history documented, of whom
      60 (78%) were sexually active. STI screens were offered to 58/60 (97%) of those
      who were sexually active and accepted by 53 (91%). Twelve (23%) of these had an
      STI. A recreational drug history was taken in 63 (74%) with 17 (27%) reporting
      use and 3 (5%) chemsex. The high rate of STIs highlights that regular screening
      in this group is essential. Additionally, the fact that over a quarter reported
      recreational drug use and given the increasing concern around chemsex, questions
      about this should be incorporated into the sexual history proforma.

PMID- 27872324
TI  - From Nitrate to Nitric Oxide: The Role of Salivary Glands and Oral Bacteria.
AB  - The salivary glands and oral bacteria play an essential role in the conversion
      process from nitrate (NO3-) and nitrite (NO2-) to nitric oxide (NO) in the human
      body. NO is, at present, recognized as a multifarious messenger molecule with
      important vascular and metabolic functions. Besides the endogenous L-arginine
      pathway, which is catalyzed by complex NO synthases, nitrate in food contributes
      to the main extrinsic generation of NO through a series of sequential steps (NO3-
      NO2--NO pathway). Up to 25% of nitrate in circulation is actively taken up by the
      salivary glands, and as a result, its concentration in saliva can increase 10- to
      20-fold. However, the mechanism has not been clearly illustrated until recently,
      when sialin was identified as an electrogenic 2NO3-/H+ transporter in the plasma
      membrane of salivary acinar cells. Subsequently, the oral bacterial species
      located at the posterior part of the tongue reduce nitrate to nitrite, as
      catalyzed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as
      final electron acceptors in their respiration and meanwhile help the host to
      convert nitrate to NO as the first step. This review describes the role of
      salivary glands and oral bacteria in the metabolism of nitrate and in the
      maintenance of NO homeostasis. The potential therapeutic applications of oral
      inorganic nitrate and nitrite are also discussed.

PMID- 27872325
TI  - The Molecular Circuit Regulating Tooth Development in Crocodilians.
AB  - Alligators have robust regenerative potential for tooth renewal. In contrast,
      extant mammals can either renew their teeth once (diphyodont dentition, as found
      in humans) or not at all (monophyodont dentition, present in mice). Previously,
      the authors used multiple mitotic labeling to map putative stem cells in
      alligator dental laminae, which contain quiescent odontogenic progenitors. The
      authors demonstrated that alligator tooth cycle initiation is related to beta
      catenin/Wnt pathway activity in the dental lamina bulge. However, the molecular
      circuitry underlying the developmental progression of polyphyodont teeth remains
      elusive. Here, the authors used transcriptomic analyses to examine the additional
      molecular pathways related to the process of alligator tooth development. The
      authors collected juvenile alligator dental laminae at different developmental
      stages and performed RNA-seq. This data shows that Wnt, bone morphogenetic
      protein (BMP), and fibroblast growth factor (FGF) pathways are activated at the
      transition from pre-initiation stage (bud) to initiation stage (cap).
      Intriguingly, the activation of Wnt ligands, receptors and co-activators
      accompanies the inactivation of Wnt antagonists. In addition, the authors
      identified the molecular circuitry at different stages of tooth development. The
      authors conclude that multiple pathways are associated with specific stages of
      tooth development in the alligator. This data shows that Wnt pathway activation
      may play the most important role in the initiation of tooth development. This
      result may offer insight into ways to modulate the genetic controls involved in
      mammalian tooth renewal.

PMID- 27872326
TI  - Pre-exposure prophylaxis (PrEP) for men who have sex with men in Europe: review
      of evidence for a much needed prevention tool.
AB  - In many Western countries with good coverage of antiretroviral treatment (ART)
      programmes the annual number of HIV infections is still high and not (yet)
      declining among men who have sex with men (MSM). This might indicate that
      antiretroviral treatment roll-out alone will not turn around the course of the
      epidemic and that new, additional tools are needed. Antiretrovirals used as
      prevention tools for people not yet infected with HIV, such as pre-exposure
      prophylaxis (PrEP) could be such important additional tools. PrEP is a new type
      of biomedical prevention, which involves the use of antiretrovirals before,
      during and after (periods of) sexual exposure to HIV. In this review, we will
      focus on PrEP as a new prevention tool for MSM at high risk in Europe, including
      its evidence for effectiveness, challenges for implementation, ongoing European
      demonstration studies; as well as how PrEP relates to other existing prevention
      tools. In light of European Medicines Agency's recent recommendation for approval
      of PrEP we briefly review the potential implications.

PMID- 27872327
TI  - Relation between cardiovascular disease risk factors and epicardial adipose
      tissue density on cardiac computed tomography in patients at high risk of
      cardiovascular events.
AB  - Background The radiodensity of epicardial adipose tissue may provide information
      on cardiovascular risk in addition to epicardial adipose tissue volume. The aim
      of this study was to quantify the relation between cardiovascular risk factors
      and the radiodensity of epicardial adipose tissue in patients at high risk of
      cardiovascular disease. Design This was a cross-sectional study in 140 patients
      at high risk of cardiovascular disease. Methods Patients from the Secondary
      Manifestations of ARTerial disease (SMART) cohort study were invited to undergo
      cardiac computed tomography angiography. The radiodensity (in Hounsfield units;
      HU) and volume (in cm3) of epicardial adipose tissue were quantified semi
      automatically. Multivariable linear regression was used to quantify the relation
      between cardiovascular risk factors and the radiodensity of epicardial adipose
      tissue. Results The cardiovascular risk factors most strongly associated with
      epicardial adipose tissue density were sex, body mass index and visceral fat,
      with a lower adipose tissue attenuation of 3.5 HU (95% confidence interval (CI)
      2.0-5.0 HU) for female sex, 1.6 HU (95%CI 0.2-2.9 HU) for body mass index >25
      kg/m2 and 1.3 HU (95% CI 0.6-2.0 HU) for a one standard deviation higher quantity
      of visceral fat, adjusted for age, sex, coronary artery bypass graft history and
      epicardial adipose tissue volume. Conclusion Low epicardial adipose tissue
      computed tomography attenuation is associated with an adverse cardiovascular risk
      factor profile in patients at high risk of cardiovascular disease, independent of
      the volume of epicardial adipose tissue and waist circumference. These findings
      support the potential role for epicardial adipose tissue radiodensity as a valid
      biomarker of cardiovascular risk. Adipose tissue radiodensity may be a more
      sensitive marker than epicardial adipose tissue volume with which to study the
      contribution of epicardial adipose tissue to the coronary atheromatous disease
      process.

PMID- 27872328
TI  - Zotepine-associated vitamin B12 deficiency and pancytopenia.

PMID- 27872329
TI  - Are antidepressants a double-edged sword? Treatment emergent affective switch or
      antidepressant discontinuation syndrome.

PMID- 27872330
TI  - Psychosocial recovery following community disasters: An international
      collaboration.

PMID- 27872331
TI  - Systemic hypersensitivity to fosaprepitant - A report of two cases.
AB  - Fosaprepitant is a widely administered antiemetic used mainly for moderately to
      highly emetogenic chemotherapy. Local injection site reactions are the most
      common type of infusion reaction reported from fosaprepitant. At our institution,
      two separate patients have experienced systemic hypersensitivity reactions to
      their infusions of fosaprepitant. We report a review of the literature and the
      details of these reactions.

PMID- 27872332
TI  - Estimates of Intraclass Correlation Coefficients and Other Design Parameters for
      Studies of School-Based Nutritional Interventions.
AB  - INTRODUCTION: When cluster randomized trials are used to evaluate school-based
      nutritional interventions such as school lunch programs, design-stage estimates
      of the required sample size must take into account the correlation in outcomes
      among individuals within each cluster (e.g., classrooms, schools, or districts).
      Estimates of the necessary parameters have been carefully developed for
      educational interventions, but for nutritional interventions the literature is
      thin. METHODS: Using data from two large multi-school, multi-district impact
      evaluations conducted in the United States, this article calculates estimates of
      the design parameters required for sizing school-based nutritional studies. The
      large size of the trials (252 and 1,327 schools) yields precise estimates of the
      parameters of interest. Variance components are estimated by fitting random
      intercept multilevel models in Stata. RESULTS: School-level intraclass
      correlations are similar to those typically found for educational outcomes. In
      particular, school-level estimates range from less than .01 to .26 across the two
      studies, and district-level estimates ranged from less than .01 to .19. This
      suggests that cluster randomized trials of nutritional interventions may require
      samples with numbers of schools similar to the education studies to detect
      similar effect sizes.

PMID- 27872333
TI  - Three-Dimensional Analysis of Enamel Crack Behavior Using Optical Coherence
      Tomography.
AB  - The aim of this study was to nondestructively analyze enamel crack behavior on
      different areas of teeth using 3D swept source-optical coherence tomography (SS
      OCT). Ten freshly extracted human teeth of each type on each arch ( n = 80 teeth)
      were inspected for enamel crack patterns on functional, contact and
      nonfunctional, or noncontact areas using 3D SS-OCT. The predominant crack pattern
      for each location on each specimen was noted and analyzed. The OCT observations
      were validated by direct observations of sectioned specimens under confocal laser
      scanning microscopy (CLSM). Cracks appeared as bright lines with SS-OCT, with 3
      crack patterns identified: Type I - superficial horizontal cracks; Type II -
      vertically (occluso-gingival) oriented cracks; and Type III - hybrid or
      complicated cracks, a combination of a Type I and Type III cracks, which may or
      may not be confluent with each other. Type II cracks were predominant on
      noncontacting surfaces of incisors and canines and nonfunctional cusps of
      posterior teeth. Type I and III cracks were predominant on the contacting
      surfaces of incisors, cusps of canines, and functional cusps of posterior teeth.
      Cracks originating from the dental-enamel junction and enamel tufts, crack
      deflections, and the initiation of new cracks within the enamel (internal cracks)
      were observed as bright areas. CLSM observations corroborated the SS-OCT
      findings. We found that crack pattern, tooth type, and the location of the crack
      on the tooth exhibited a strong correlation. We show that the use of 3D SS-OCT
      permits for the nondestructive 3D imaging and analysis of enamel crack behavior
      in whole human teeth in vitro. 3D SS-OCT possesses potential for use in clinical
      studies for the analysis of enamel crack behavior.

PMID- 27872336
TI  - Effect of Free Sugars on Diabetes, Obesity, and Dental Caries.

PMID- 27872334
TI  - Antimicrobial Peptides: Mechanisms of Action and Resistance.
AB  - More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral
      cavity. These AMPs have been organized into 6 functional groups, 1 of which,
      cationic AMPs, has received extensive attention in recent years for their promise
      as potential antibiotics. The goal of this review is to describe recent advances
      in our understanding of the diverse mechanisms of action of cationic AMPs and the
      bacterial resistance against these peptides. The recently developed peptide GL13K
      is used as an example to illustrate many of the discussed concepts. Cationic AMPs
      typically exhibit an amphipathic conformation, which allows increased interaction
      with negatively charged bacterial membranes. Peptides undergo changes in
      conformation and aggregation state in the presence of membranes; conversely,
      lipid conformation and packing can adapt to the presence of peptides. As a
      consequence, a single peptide can act through several mechanisms depending on the
      peptide's structure, the peptide:lipid ratio, and the properties of the lipid
      membrane. Accumulating evidence shows that in addition to acting at the cell
      membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme
      activity, or act intracellularly. Therefore, once a peptide has reached the cell
      wall, cell membrane, or its internal target, the difference in mechanism of
      action on gram-negative and gram-positive bacteria may be less pronounced than
      formerly assumed. While AMPs should not cause widespread resistance due to their
      preferential attack on the cell membrane, in cases where specific protein targets
      are involved, the possibility exists for genetic mutations and bacterial
      resistance. Indeed, the potential clinical use of AMPs has raised the concern
      that resistance to therapeutic AMPs could be associated with resistance to
      endogenous host-defense peptides. Current evidence suggests that this is a rare
      event that can be overcome by subtle structural modifications of an AMP.

PMID- 27872338
TI  - Re: Visual and auditory cortical evoked potentials in interictal episodic
      migraine: An audit on 624 patients from three centres.

PMID- 27872339
TI  - Visual and auditory cortical evoked potentials in interictal episodic migraine:
      An audit on 624 patients from three centres. Response to the letter by Omland et
      al.

PMID- 27872342
TI  - Intrinsic median nerve compression by a bone fragment following distal radius
      fracture.

PMID- 27872341
TI  - Amygdala Circuits for Fear Memory: A Key Role for Dopamine Regulation.
AB  - In addition to modulating a number of cognitive functions including reward,
      punishment, motivation, and salience, dopamine (DA) plays a pivotal role in
      regulating threat-related emotional memory. Changes in neural circuits of the
      amygdala nuclei are also critically involved in the acquisition and expression of
      emotional memory. In this review, we summarize the regulation of amygdala
      circuits by DA. Specifically, we describe DA signaling in the amygdala, and DA
      regulation of synaptic transmission and synaptic plasticity of the amygdala
      neurons. Finally, we discuss a potential contribution of DA-related mechanisms to
      the pathogenesis of posttraumatic stress disorder.

PMID- 27872340
TI  - Evaluating the Needs of Patients Living With Solid Tumor Cancer: A Survey Design.
AB  - PURPOSE: To describe the unmet needs of adult patients living with solid tumor
      cancer. DESIGN: Survey design. METHOD: Adult patients living with solid tumor
      cancer from two outpatient clinics were mailed the Sheffield Profile for
      Assessment and Referral to Care, a holistic screening questionnaire for assessing
      palliative care needs, and a demographics questionnaire. One hundred fifteen
      patients returned the instruments, corresponding to a 62% response rate.
      FINDINGS: There were no significant differences by cancer type (breast, non
      breast) or gender. However, Caucasians reported significantly more psychological
      issues, such as anxiety, than non-Caucasians ([ n = 101 (87.8%)] and [ n = 14
      (12.2%)], respectively, p = .032). Older patients reported more concerns about
      loss of independence/activity ( p = .012) compared with younger age groups.
      Patients living with Stage III/IV cancer reported more distressed about
      independence/activity ( p = .034), family/social issues ( p = .007), and
      treatment side effects ( p = .027) than patients living with Stage I/II cancer.
      CONCLUSION: Patients living with solid tumor cancer have a myriad of unmet needs
      regardless of age, gender, cancer type, or cancer stage. There appears to be
      important differences by cancer stage. The Sheffield Profile for Assessment and
      Referral to Care questionnaire provides a holistic approach for nurses to
      identify unmet needs and concerns. Future research should explore the preferred
      methods of receiving support and information.

PMID- 27872343
TI  - Recovery, responsiveness and interpretability of patient-reported outcome
      measures after surgery for Dupuytren's disease.
AB  - : This prospective cohort study investigated the responsiveness and
      interpretability of the Disabilities of the Arm, Shoulder and Hand (DASH) and
      Unite Rhumatologique des Affections de la Main (URAM) outcome measures for
      assessing recovery after fasciectomy and dermofasciectomy for Dupuytren's
      disease. DASH outcome scores at 1 year were significantly better than at 6 weeks,
      suggesting that recovery is not complete by 6 weeks. Of the 101 patients
      recruited to the DASH cohort, 71 completed preoperative, 6 week and 1 year
      postoperative DASH scores; 68 of them completed preoperative and 1 year
      postoperative DASH scores and an external anchor question. In the URAM cohort,
      30/44 completed the preoperative and the 1 year postoperative URAM scores and the
      anchor question. The DASH score exhibited moderate responsiveness but poor
      interpretability on receiver operating characteristic curve analysis, such that a
      minimal important change could not be estimated. The URAM score showed acceptable
      responsiveness, and an MIC of 10.5 on receiver operating characteristic analysis.
      LEVEL OF EVIDENCE: II.

PMID- 27872344
TI  - Impact of non-menthol flavours in tobacco products on perceptions and use among
      youth, young adults and adults: a systematic review.
AB  - OBJECTIVE: This systematic review examines the impact of non-menthol flavours in
      tobacco products on tobacco use perceptions and behaviours among youth, young
      adults and adults. DATA SOURCES: English-language peer-reviewed publications
      indexed in 4 databases were searched through April 2016. STUDY SELECTION: A
      search strategy was developed related to tobacco products and flavours. Of 1688
      articles identified, we excluded articles that were not English-language, were
      not peer-reviewed, were qualitative, assessed menthol-flavoured tobacco products
      only and did not contain original data on outcomes that assessed the impact of
      flavours in tobacco products on perceptions and use behaviour. DATA EXTRACTION:
      Outcome measures were identified and tabulated. 2 researchers extracted the data
      independently and used a validated quality assessment tool to assess study
      quality. DATA SYNTHESIS: 40 studies met the inclusion criteria. Data showed that
      tobacco product packaging with flavour descriptors tended to be rated as more
      appealing and as less harmful by tobacco users and non-users. Many tobacco
      product users, especially adolescents, reported experimenting, initiating and
      continuing to use flavoured products because of the taste and variety of the
      flavours. Users of many flavoured tobacco products also showed decreased
      likelihood of intentions to quit compared with non-flavoured tobacco product
      users. CONCLUSIONS: Flavours in most tobacco products appear to play a key role
      in how users and non-users, especially youth, perceive, initiate, progress and
      continue using tobacco products. Banning non-menthol flavours from tobacco
      products may ultimately protect public health by reducing tobacco use,
      particularly among youth.

PMID- 27872346
TI  - Use of new media to support passage of Vietnam's national tobacco control
      legislation.

PMID- 27872347
TI  - Toward an Empirical Multidimensional Structure of Anhedonia, Reward Sensitivity,
      and Positive Emotionality: An Exploratory Factor Analytic Study.
AB  - Positive emotionality, anhedonia, and reward sensitivity share motivational and
      experiential elements of approach motivation and pleasure. Earlier work has
      examined the interrelationships among these constructs from measures of
      extraversion. More recently, the Research Domain Criteria introduced the Positive
      Valence Systems as a primary dimension to better understand psychopathology.
      However, the suggested measures tapping this construct have not yet been
      integrated within the structural framework of personality, even at the level of
      self-report. Thus, this study conducted exploratory factor and exploratory
      bifactor analyses on 17 different dimensions relevant to approach motivation,
      spanning anhedonia, behavioral activation system functioning, and positive
      emotionality. Convergent validity of these dimensions is tested by examining
      associations with depressive symptoms. Relying on multiple indices of fit, our
      preferred model included a general factor along with specific factors of
      affiliation, positive emotion, assertiveness, and pleasure seeking. These factors
      demonstrated different patterns of association with depressive symptoms. We
      discuss the plausibility of this model and highlight important future directions
      for work on the structure of a broad Positive Valence Systems construct.

PMID- 27872348
TI  - Resolving Dimensionality Problems With WHOQOL-BREF Item Responses.
AB  - The World Health Organization Quality of Life Scale (WHOQOL-BREF) is predicated
      on a multidimensional perspective on quality of life (QOL); yet studies are
      unclear about the latent structure underlying responses. This article reports on
      a study conducted to investigate the structure of WHOQOL-BREF scores. Competing
      latent structures of the data were examined in a general population sample. In
      addition, the complete factorial invariance of the retained model was
      investigated across gender. We also investigated latent mean differences in the
      QOL dimensions over age as well as age by gender interactions effects. Based on
      responses to the WHOQOL-BREF, support was found for a bifactor exploratory
      structural equation modeling representation of the data. This measurement
      structure accounts for construct-relevant multidimensionality in item responses
      due to the presence of general and specific factors underlying the data and the
      fallibility of indictors as pure reflections of only the single constructs they
      are purported to measure. Furthermore, support was found for measurement and
      structural invariance across gender. Finally, evidence was obtained for a
      curvilinear relationship of age with QOL, characterized by a midlife nadir. Taken
      together, the results of the study yield important validation data for the WHOQOL
      BREF and tentatively resolve the dimensionality issues in the measurement of QOL
      using this instrument.

PMID- 27872345
TI  - Hazards of cigarettes, smokeless tobacco and waterpipe in a Middle Eastern
      Population: a Cohort Study of 50 000 individuals from Iran.
AB  - BACKGROUND: There is limited information about the hazards of cigarettes,
      smokeless tobacco and waterpipe in the Middle East. The aim of this study was to
      determine the association between different types of tobacco use and earlier
      death in the Golestan Cohort Study. METHODS: The Study includes 50 045 adults
      (aged 40-75 years) from north eastern Iran. The baseline questionnaire (2004
      2008) assessed information about use of cigarettes, chewing tobacco (nass) and
      waterpipe. To assess the use of each type of tobacco compared with never tobacco
      users, we used Cox regression models adjusted for age, socioeconomic status, area
      of residence, education and other tobacco used, and stratified by sex, ethnicity
      and opium use. RESULTS: 17% of participants reported a history of cigarette
      smoking, 7.5% chewing tobacco (nass) and 1.1% smoking waterpipe, and these
      figures declined in the later birth cohorts. During a median follow-up of 8
      years, 4524 deaths occurred (mean age 64.8+9.9 years). Current (HR=1.44; 95% CI
      1.28 to 1.61) and former (HR=1.35; 95% CI 1.16 to 1.56) cigarette smokers had
      higher overall mortality relative to never tobacco users. The highest cigarette
      associated risk was for cancer death among current heavy smokers (HR=2.32; 95% CI
      1.66 to 3.24). Current nass chewing was associated with overall mortality
      (HR=1.16; 95% CI 1.01 to 1.34), and there was a 61% higher risk of cancer death
      in people chewing nass more than five times a day. We observed an association
      between the cumulative lifetime waterpipe use (waterpipe-years>=28) and both
      overall (HR=1.66; 95% CI 1.11 to 2.47), and cancer mortality (HR=2.82; 95% CI
      1.30 to 6.11). CONCLUSIONS: Regular use of cigarettes, smokeless tobacco and
      waterpipe were associated with the risk of earlier death (particularly from
      cancer) in our cohort.

PMID- 27872349
TI  - Bifactor Models of Attention-Deficit/Hyperactivity Disorder (ADHD): An Evaluation
      of Three Necessary but Underused Psychometric Indexes.
AB  - BACKGROUND: In the past decade, the bifactor model of attention
      deficit/hyperactivity disorder (ADHD) has been extensively researched. This model
      consists of an ADHD general dimension and two specific factors: inattention and
      hyperactivity/impulsivity. All studies conclude that the bifactor is superior to
      the traditional two-correlated factors model, according to the fit obtained by
      factor analysis. However, the proper interpretation of a bifactor not only
      depends on the fit but also on the quality of the measurement model. OBJECTIVE:
      To evaluate the model-based reliability, distribution of common variance and
      construct replicability of general and specific ADHD factors. METHOD: We
      estimated expected common variance, omega hierarchical/subscale and H-index from
      standardized factor loadings of 31 ADHD bifactor models previously published.
      RESULTS AND CONCLUSION: The ADHD general factor explained most of the common
      variance. Given the low reliable variance ratios, the specific factors were
      difficult to interpret. However, in clinical samples, inattention acquired
      sufficient specificity and stability for interpretation beyond the general
      factor. Implications for research and clinical practice are discussed.

PMID- 27872350
TI  - Simultaneous acquisition of high-contrast and quantitative liver T1 images using
      3D phase-sensitive inversion recovery: a feasibility study.
AB  - Background Tumor-to-liver contrast is low in images of chronically diseased
      livers because gadolinium-based hepatocyte-specific contrast agents (Gd-EOB-DTPA)
      accumulate less to hepatocytes. Purpose To determine whether phase-sensitive
      inversion recovery (PSIR) could improve the T1 contrasts of Gd-based contrast
      agents and liver parenchyma and simultaneously provide accurate T1 values for
      abdominal organs. Material and Methods The image contrasts of phantoms with
      different Gd concentrations that were obtained using PSIR were compared to
      conventional turbo field echo (TFE) results. T1 value was estimated using PSIR by
      performing iterations to investigate the two IR magnetization evolutions. The
      estimated T1 values were validated using IR-spin echo (IR-SE) and Look-Locker (L
      L) sequences. In an in vivo study, the liver-to-spleen and liver-to-muscle
      contrasts of the PSIR and TFE images of seven volunteers were compared, as were
      the T1 values of liver parenchyma, spleen, and muscle obtained using PSIR and L-L
      sequences. Results The PSIR images showed T1 contrasts higher than those in the
      TFE results. The PSIR and IR-SE T1 values were linearly correlated. Additionally,
      the R1 estimated using PSIR were correlated with those measured using IR-SE and L
      L. In the in vivo study, the liver-to-spleen and liver-to-muscle contrasts of
      PSIR were significantly higher than those obtained using TFE. T1 values of
      abdominal organs obtained using PSIR and L-L were clearly correlated. Conclusion
      PSIR may be capable of improving liver image T1 contrasts when Gd-based contrast
      agents are employed and simultaneously yielding accurate T1 values of abdominal
      organs.

PMID- 27872351
TI  - Uterine fibroid embolization with acrylamido polyvinyl microspheres: prospective
      12-month clinical and MRI follow-up study.
AB  - Background Uterine fibroid embolization (UFE) is an effective minimally invasive
      treatment aimed to obtain complete fibroid infarction. Purpose To evaluate the
      degree of fibroid infarction after embolization with acrylamido polyvinyl alcohol
      microspheres (Bead Block). Material and Methods This prospective study included
      26 pre-menopausal women in the period October 2013 to January 2015. UFE with the
      use of Bead Block microspheres 700-900 um was obtained until flow stasis was
      achieved. Contrast-enhanced magnetic resonance imaging (MRI) was used to define
      residual contrast enhancement in the total fibroid burden and enhancement >10%
      was defined as insufficient embolization. The dominant fibroid volume and total
      uterine volume changes were assessed. Clinical outcome was analyzed using the
      quality of life questionnaire (UFS-QOL). Results Twenty-four of the 26 patients
      (92%) had a technically successful UFE with complete flow-stop in both uterine
      arteries. Twenty-two of the 26 patients (85%) completed 3 months of MRI control
      and 20 patients (77%) completed 12 months of MRI control. There were 16 of 22
      patients (73%) with complete fibroid burden infarction and/or without residual
      contrast enhancement of the fibroids of more than 10% at 3 months of control. Six
      of 22 patients (27%) had insufficient fibroid burden infarction with residual
      contrast enhancement of more than 10%. Twenty-two and 18 of 26 patients completed
      the 3-month and 12-month questionnaire, respectively. UFS-QOL analyses showed
      that 91% of the patients had significant clinical improvement. Conclusion Sixteen
      of the 22 patients had complete fibroid burden infarction using Bead Block
      microspheres (700-900 um); however, unacceptably high insufficient fibroid burden
      infarction in almost one-fourth of the patients were recorded.

PMID- 27872353
TI  - Feed and Wrap MRI Technique in Infants.
AB  - The feed and wrap technique refers to the use of feeding and swaddling to induce
      natural sleep in infants. It can be used prior to an magnetic resonance imaging
      (MRI) scan, avoiding sedation or anesthesia. We performed a retrospective review
      of feed and wrap MRI scans in infants 3 months or younger over a 2-year period at
      our center (279 scans) to evaluate the efficacy of this technique. Of scan
      results reviewed, 79% addressed the clinical question, 20% partially addressed
      the clinical question, and 1% were technically inadequate. History of preterm
      birth (odds ratio [OR] = 2.368; P = .032) and spine MRI (OR = 2.821; P = .001)
      were associated with a less-successful scan outcome. The feed and wrap technique
      can be used successfully in infants undergoing MRI; however, it may be less
      successful in preterm infants and those requiring spinal MRI. A standardized
      technique performed by experienced personnel may avoid anesthesia and sedation in
      infants who require MRI.

PMID- 27872352
TI  - Additional functional outcomes after endovascular treatment for intermittent
      claudication.
AB  - Background Endovascular treatment (EVT) for intermittent claudication (IC) is
      performed in selected patients where conservative treatment and training fail.
      Treatment outcomes reported in vascular registries (survival, limb-survival, and
      re-intervention rate) are inadequate for low-risk patients with IC. Additional
      measurements of blood flow reduction and functional impairment clarify the
      indication for treatment and facilitate outcome evaluation. Purpose To analyze
      the additional outcome information on peripheral arterial pressures and walking
      capacity obtained from a local registry of EVT. Material and Methods Patients
      with IC treated with endovascular technique (angioplasty or stent) were
      prospectively entered into a local registry in addition to the national registry
      (NORKAR), with information on arterial pressures (ankle brachial index [ABI]) and
      treadmill performance (maximum walking distance [MWD]). Results A total of 242
      consecutive patients (41% women; median age, 70 years) receiving the first
      treatment between July 2010 and December 2012 were included, 61% with aorto-iliac
      lesions. After 3 months, mean ABI increased from 0.62 (0.59-0.64) to 0.85 (0.83
      0.87). The median MWD increased from 160 m to 410 m. Sixty-two percent reached
      the test maximum of 10 min. The improvement in ABI and MWD persisted after 1
      year. When preoperative ABI was moderately reduced (0.5-0.9), ABI was normal in
      61% after 3 months and in 55% after 1 year. When preoperative ABI was low (<0.5),
      ABI was normal in 43% both after 3 months and 1 year. Conclusion ABI and walking
      capacity were important outcome variables and improved after EVT. ABI improvement
      was better for patients with moderately reduced preoperative ABI than with low
      ABI.

PMID- 27872354
TI  - Integrating Maternal Mental Health Care in the Pediatric Medical Home: Treatment
      Engagement and Child Outcomes.
AB  - Maternal depression is associated with an array of poor child health outcomes,
      and low-income women face many barriers to accessing treatment. In this pilot
      study, we assessed treatment engagement in a maternal mental health clinic
      staffed by a case manager and psychiatrist in an urban pediatric practice. We
      also examined factors associated with engagement as well as child health outcomes
      and health care use. Nearly half of the women enrolled attended at least 4
      sessions with a psychiatrist in 6 months. Text messaging with the case manager
      was associated with a greater compliance with psychiatrist sessions. Comparing
      index children with their siblings prior to enrollment, a higher percentage had
      immunizations up to date at 1 year of age (82% vs 43%, P = .01), and well-child
      visit compliance trended toward significance (65% vs 35%, P = .06). The pediatric
      setting holds promise as an innovative venue to deliver maternal mental health
      care.

PMID- 27872356
TI  - Middle East Respiratory Syndrome Coronavirus and Children.

PMID- 27872355
TI  - Acceptance of Pharmacist-Driven Antimicrobial Stewardship Recommendations With
      Differing Levels of Physician Involvement in a Children's Hospital.
AB  - This prospective interventional study assessed whether a pharmacist-physician
      team in a setting where physician support is not provided for daily antimicrobial
      stewardship (AS) activities would improve later acceptance of pharmacist
      recommendations once multidisciplinary efforts stopped and the pharmacist again
      worked alone. This was measured by AS recommendation acceptance rate during 3
      study phases wherein AS recommendations were provided by a pharmacist alone
      (Phase 1), a pharmacist and a physician together (Phase 2), and then a pharmacist
      alone again (Phase 3). Recommendations were well accepted across all study phases
      with no differences in recommendation appropriateness or patient clinical
      outcomes. Prescribers were significantly ( P = .045) more likely to accept
      recommendations to de-escalate treatment during Phase 3 than during Phase 1.
      Independently pharmacist-driven AS efforts were generally successful, and
      recommendations for antimicrobial de-escalation were better accepted after the
      involvement of an infectious diseases physician.

PMID- 27872357
TI  - Antipyretic Efficacy and Safety of Ibuprofen Versus Acetaminophen Suspension in
      Febrile Children: Results of 2 Randomized, Double-Blind, Single-Dose Studies.
AB  - Two blinded single-dose studies randomized children 6 months to 11 years old with
      fever to receive ibuprofen (IBU) pediatric suspension 7.5 mg/kg or acetaminophen
      (APAP) suspension 10 to 15 mg/kg. The primary efficacy parameter was time
      weighted sum of temperature differences (TWSTD) from baseline through 8 hours for
      each study. Secondary end points included TWSTD from baseline through 6 hours,
      time to onset and duration of temperature control, and proportion with
      temperature control. Studies were pooled for post hoc analyses of efficacy and
      adverse event end points. The primary efficacy parameter significantly favored
      IBU over APAP in study 1 and the pooled analysis (both P < .001), but was not
      significant in study 2. Onset of temperature control significantly favored IBU in
      study 2 ( P = .007). Individual and pooled secondary efficacy outcomes supported
      significant advantages ( P < .05) of IBU over APAP. IBU pediatric suspension
      provided greater temperature reduction versus acetaminophen in febrile children,
      with a comparable safety profile.

PMID- 27872358
TI  - Severe Obesity Decreasing in Children in Cincinnati, Ohio.
AB  - Childhood obesity rates appear to be leveling off. Studies not looking at severe
      obesity may be masking a rightward shift in the distribution of body mass
      indexes. Our objective was to provide current prevalence rates and examine trends
      in overweight, obesity, class 2 obesity, and class 3 obesity for youth in
      Cincinnati, Ohio. We performed a retrospective chart review of children 2 to 18
      years old seen at Cincinnati Children's Hospital Medical Center between July 1,
      2011, and June 30, 2014. Data from 217 037 BMIs were obtained; 35.2% of children
      were found to have an elevated BMI. Prevalence rates were highest in older,
      Hispanic, and Medicaid-insured children. The only significant trend over the 3
      year period was a downward shift in class 3 obesity ( P = .02), contrary to
      national findings. Further studies assessing which clinical/community efforts
      have led to this downward trend will be essential to target future resources and
      facilitate continued progress.

PMID- 27872359
TI  - Child Sleep Coaches: Current State and Future Directions.
AB  - Given the genuine gaps in the availability of clinical sleep services for
      children, sleep coaching as a field has emerged and appears to be significantly
      increasing. Sleep coaches are typically individuals who provide individualized
      services, often via the Internet or phone, to families of infants and young
      children (and increasingly to older children, adolescents, and adults as well)
      with sleep problems. At this time, there is no universally accepted definition of
      sleep coach, nor are there clear guidelines regarding educational background,
      training requirements, scope of practice, or credentialing. To start to address
      the needs of families seeking the services of a sleep coach, educational
      materials were developed for parents and health care providers regarding issues
      to consider. Furthermore, there is a need going forward that (1) the designation
      sleep coach or consultant be clear and well defined, with a clear standard of
      care and scope of practice; (2) there is a standard core body of knowledge
      included in all training programs; (3) a certification process is developed for
      sleep coaches that is reputable and has recognizable and clear standards; and (4)
      that care for sleep problems in infants and young children are available to
      diverse populations, irrespective of socioeconomic status.

PMID- 27872360
TI  - The Heidelberg Appendicitis Score Predicts Perforated Appendicitis in Children.
AB  - BACKGROUND: In the future, surgical management of pediatric appendicitis might
      become limited to nonperforating appendicitis. Thus, it becomes increasingly
      important to differentiate advanced from simple appendicitis and to predict
      perforated appendicitis among a group of children with right-sided abdominal
      pain, which was the aim of this study. METHODS: An institutionally approved,
      single-center retrospective analysis of all patients with appendectomy from
      January 2009 to December 2010 was conducted. All diagnostic aspects were
      evaluated to identify predictors and differentiators of perforated appendicitis.
      RESULTS: In 2 years, 157 children suffered from appendicitis. Perforation
      occurred in 47 (29.9%) of the patients. C-reactive protein (CRP) levels higher
      than 20 mg/dL ( P = .037) and free abdominal fluid on ultrasonography ( P = .031)
      are the most important features to differentiate perforated from simple
      appendicitis. Moreover, all children with perforation had a positive Heidelberg
      Appendicitis Score (HAS). A negative HAS excludes perforation in all cases
      (negative predictive value = 100%). DISCUSSION: Perforated appendicitis can be
      ruled out by the HAS. In a cohort with right-sided abdominal pain, perforation
      should be considered in children with high CRP levels and free fluids or abscess
      formation on ultrasound.

PMID- 27872361
TI  - A 19-Year-Old Woman With Increased Urinary Frequency, Abdominal and Back Pain.

PMID- 27872362
TI  - Fever, Jaundice, and Confusion.

PMID- 27872363
TI  - Prolonged Fevers in a Previously Healthy Child.

PMID- 27872364
TI  - Zika Virus.

PMID- 27872365
TI  - Ankle Pain, a Swollen Neck, and a Gallop.

PMID- 27872366
TI  - The long road of statistical learning research: past, present and future.

PMID- 27872367
TI  - The neurobiology of uncertainty: implications for statistical learning.
AB  - The capacity for assessing the degree of uncertainty in the environment relies on
      estimating statistics of temporally unfolding inputs. This, in turn, allows
      calibration of predictive and bottom-up processing, and signalling changes in
      temporally unfolding environmental features. In the last decade, several studies
      have examined how the brain codes for and responds to input uncertainty. Initial
      neurobiological experiments implicated frontoparietal and hippocampal systems,
      based largely on paradigms that manipulated distributional features of visual
      stimuli. However, later work in the auditory domain pointed to different systems,
      whose activation profiles have interesting implications for computational and
      neurobiological models of statistical learning (SL). This review begins by
      briefly recapping the historical development of ideas pertaining to the
      sensitivity to uncertainty in temporally unfolding inputs. It then discusses
      several issues at the interface of studies of uncertainty and SL. Following, it
      presents several current treatments of the neurobiology of uncertainty and
      reviews recent findings that point to principles that serve as important
      constraints on future neurobiological theories of uncertainty, and relatedly, SL.
      This review suggests it may be useful to establish closer links between
      neurobiological research on uncertainty and SL, considering particularly
      mechanisms sensitive to local and global structure in inputs, the degree of input
      uncertainty, the complexity of the system generating the input, learning
      mechanisms that operate on different temporal scales and the use of learnt
      information for online prediction.This article is part of the themed issue 'New
      frontiers for statistical learning in the cognitive sciences'.

PMID- 27872368
TI  - Complementary learning systems within the hippocampus: a neural network modelling
      approach to reconciling episodic memory with statistical learning.
AB  - A growing literature suggests that the hippocampus is critical for the rapid
      extraction of regularities from the environment. Although this fits with the
      known role of the hippocampus in rapid learning, it seems at odds with the idea
      that the hippocampus specializes in memorizing individual episodes. In
      particular, the Complementary Learning Systems theory argues that there is a
      computational trade-off between learning the specifics of individual experiences
      and regularities that hold across those experiences. We asked whether it is
      possible for the hippocampus to handle both statistical learning and memorization
      of individual episodes. We exposed a neural network model that instantiates known
      properties of hippocampal projections and subfields to sequences of items with
      temporal regularities. We found that the monosynaptic pathway-the pathway
      connecting entorhinal cortex directly to region CA1-was able to support
      statistical learning, while the trisynaptic pathway-connecting entorhinal cortex
      to CA1 through dentate gyrus and CA3-learned individual episodes, with apparent
      representations of regularities resulting from associative reactivation through
      recurrence. Thus, in paradigms involving rapid learning, the computational trade
      off between learning episodes and regularities may be handled by separate
      anatomical pathways within the hippocampus itself.This article is part of the
      themed issue 'New frontiers for statistical learning in the cognitive sciences'.

PMID- 27872369
TI  - The impact of cerebellar transcranial direct current stimulation (tDCS) on
      learning fine-motor sequences.
AB  - The cerebellum has been shown to be important for skill learning, including the
      learning of motor sequences. We investigated whether cerebellar transcranial
      direct current stimulation (tDCS) would enhance learning of fine motor sequences.
      Because the ability to generalize or transfer to novel task variations or
      circumstances is a crucial goal of real world training, we also examined the
      effect of tDCS on performance of novel sequences after training. In Study 1,
      participants received either anodal, cathodal or sham stimulation while
      simultaneously practising three eight-element key press sequences in a non
      repeating, interleaved order. Immediately after sequence practice with concurrent
      tDCS, a transfer session was given in which participants practised three
      interleaved novel sequences. No stimulation was given during transfer. An
      inhibitory effect of cathodal tDCS was found during practice, such that the rate
      of learning was slowed in comparison to the anodal and sham groups. In Study 2,
      participants received anodal or sham stimulation and a 24 h delay was added
      between the practice and transfer sessions to reduce mental fatigue. Although
      this consolidation period benefitted subsequent transfer for both tDCS groups,
      anodal tDCS enhanced transfer performance. Together, these studies demonstrate
      polarity-specific effects on fine motor sequence learning and generalization.This
      article is part of the themed issue 'New frontiers for statistical learning in
      the cognitive sciences'.

PMID- 27872370
TI  - Language learning, language use and the evolution of linguistic variation.
AB  - Linguistic universals arise from the interaction between the processes of
      language learning and language use. A test case for the relationship between
      these factors is linguistic variation, which tends to be conditioned on
      linguistic or sociolinguistic criteria. How can we explain the scarcity of
      unpredictable variation in natural language, and to what extent is this property
      of language a straightforward reflection of biases in statistical learning? We
      review three strands of experimental work exploring these questions, and
      introduce a Bayesian model of the learning and transmission of linguistic
      variation along with a closely matched artificial language learning experiment
      with adult participants. Our results show that while the biases of language
      learners can potentially play a role in shaping linguistic systems, the
      relationship between biases of learners and the structure of languages is not
      straightforward. Weak biases can have strong effects on language structure as
      they accumulate over repeated transmission. But the opposite can also be true:
      strong biases can have weak or no effects. Furthermore, the use of language
      during interaction can reshape linguistic systems. Combining data and insights
      from studies of learning, transmission and use is therefore essential if we are
      to understand how biases in statistical learning interact with language
      transmission and language use to shape the structural properties of language.This
      article is part of the themed issue 'New frontiers for statistical learning in
      the cognitive sciences'.

PMID- 27872371
TI  - Statistical learning in songbirds: from self-tutoring to song culture.
AB  - At the onset of vocal development, both songbirds and humans produce variable
      vocal babbling with broadly distributed acoustic features. Over development,
      these vocalizations differentiate into the well-defined, categorical signals that
      characterize adult vocal behaviour. A broadly distributed signal is ideal for
      vocal exploration, that is, for matching vocal production to the statistics of
      the sensory input. The developmental transition to categorical signals is a
      gradual process during which the vocal output becomes differentiated and stable.
      But does it require categorical input? We trained juvenile zebra finches with
      playbacks of their own developing song, produced just a few moments earlier,
      updated continuously over development. Although the vocalizations of these self
      tutored (ST) birds were initially broadly distributed, birds quickly developed
      categorical signals, as fast as birds that were trained with a categorical, adult
      song template. By contrast, siblings of those birds that received no training
      (isolates) developed phonological categories much more slowly and never reached
      the same level of category differentiation as their ST brothers. Therefore,
      instead of simply mirroring the statistical properties of their sensory input,
      songbirds actively transform it into distinct categories. We suggest that the
      early self-generation of phonological categories facilitates the establishment of
      vocal culture by making the song easier to transmit at the micro level, while
      promoting stability of shared vocabulary at the group level over generations.This
      article is part of the themed issue 'New frontiers for statistical learning in
      the cognitive sciences'.

PMID- 27872372
TI  - Do infants retain the statistics of a statistical learning experience? Insights
      from a developmental cognitive neuroscience perspective.
AB  - Statistical structure abounds in language. Human infants show a striking capacity
      for using statistical learning (SL) to extract regularities in their linguistic
      environments, a process thought to bootstrap their knowledge of language.
      Critically, studies of SL test infants in the minutes immediately following
      familiarization, but long-term retention unfolds over hours and days, with almost
      no work investigating retention of SL. This creates a critical gap in the
      literature given that we know little about how single or multiple SL experiences
      translate into permanent knowledge. Furthermore, different memory systems with
      vastly different encoding and retention profiles emerge at different points in
      development, with the underlying memory system dictating the fidelity of the
      memory trace hours later. I describe the scant literature on retention of SL, the
      learning and retention properties of memory systems as they apply to SL, and the
      development of these memory systems. I propose that different memory systems
      support retention of SL in infant and adult learners, suggesting an explanation
      for the slow pace of natural language acquisition in infancy. I discuss the
      implications of developing memory systems for SL and suggest that we exercise
      caution in extrapolating from adult to infant properties of SL.This article is
      part of the themed issue 'New frontiers for statistical learning in the cognitive
      sciences'.

PMID- 27872373
TI  - Real-world visual statistics and infants' first-learned object names.
AB  - We offer a new solution to the unsolved problem of how infants break into word
      learning based on the visual statistics of everyday infant-perspective scenes.
      Images from head camera video captured by 8 1/2 to 10 1/2 month-old infants at
      147 at-home mealtime events were analysed for the objects in view. The images
      were found to be highly cluttered with many different objects in view. However,
      the frequency distribution of object categories was extremely right skewed such
      that a very small set of objects was pervasively present-a fact that may
      substantially reduce the problem of referential ambiguity. The statistical
      structure of objects in these infant egocentric scenes differs markedly from that
      in the training sets used in computational models and in experiments on
      statistical word-referent learning. Therefore, the results also indicate a need
      to re-examine current explanations of how infants break into word learning.This
      article is part of the themed issue 'New frontiers for statistical learning in
      the cognitive sciences'.

PMID- 27872375
TI  - TRACX2: a connectionist autoencoder using graded chunks to model infant visual
      statistical learning.
AB  - Even newborn infants are able to extract structure from a stream of sensory
      inputs; yet how this is achieved remains largely a mystery. We present a
      connectionist autoencoder model, TRACX2, that learns to extract sequence
      structure by gradually constructing chunks, storing these chunks in a distributed
      manner across its synaptic weights and recognizing these chunks when they re
      occur in the input stream. Chunks are graded rather than all-or-nothing in
      nature. As chunks are learnt their component parts become more and more tightly
      bound together. TRACX2 successfully models the data from five experiments from
      the infant visual statistical learning literature, including tasks involving
      forward and backward transitional probabilities, low-salience embedded chunk
      items, part-sequences and illusory items. The model also captures performance
      differences across ages through the tuning of a single-learning rate parameter.
      These results suggest that infant statistical learning is underpinned by the same
      domain-general learning mechanism that operates in auditory statistical learning
      and, potentially, in adult artificial grammar learning.This article is part of
      the themed issue 'New frontiers for statistical learning in the cognitive
      sciences'.

PMID- 27872374
TI  - What's statistical about learning? Insights from modelling statistical learning
      as a set of memory processes.
AB  - Statistical learning has been studied in a variety of different tasks, including
      word segmentation, object identification, category learning, artificial grammar
      learning and serial reaction time tasks (e.g. Saffran et al. 1996 Science 274: ,
      1926-1928; Orban et al. 2008 Proceedings of the National Academy of Sciences 105:
      , 2745-2750; Thiessen & Yee 2010 Child Development 81: , 1287-1303; Saffran 2002
      Journal of Memory and Language 47: , 172-196; Misyak & Christiansen 2012 Language
      Learning 62: , 302-331). The difference among these tasks raises questions about
      whether they all depend on the same kinds of underlying processes and
      computations, or whether they are tapping into different underlying mechanisms.
      Prior theoretical approaches to statistical learning have often tried to explain
      or model learning in a single task. However, in many cases these approaches
      appear inadequate to explain performance in multiple tasks. For example,
      explaining word segmentation via the computation of sequential statistics (such
      as transitional probability) provides little insight into the nature of
      sensitivity to regularities among simultaneously presented features. In this
      article, we will present a formal computational approach that we believe is a
      good candidate to provide a unifying framework to explore and explain learning in
      a wide variety of statistical learning tasks. This framework suggests that
      statistical learning arises from a set of processes that are inherent in memory
      systems, including activation, interference, integration of information and
      forgetting (e.g. Perruchet & Vinter 1998 Journal of Memory and Language 39: , 246
      263; Thiessen et al. 2013 Psychological Bulletin 139: , 792-814). From this
      perspective, statistical learning does not involve explicit computation of
      statistics, but rather the extraction of elements of the input into memory
      traces, and subsequent integration across those memory traces that emphasize
      consistent information (Thiessen and Pavlik 2013 Cognitive Science 37: , 310
      343).This article is part of the themed issue 'New frontiers for statistical
      learning in the cognitive sciences'.

PMID- 27872376
TI  - The multi-component nature of statistical learning.
AB  - The central argument presented in this paper is that statistical learning (SL) is
      an ability comprised of multiple components that operate largely implicitly.
      Components relating to the stimulus encoding, retention and abstraction required
      for SL may include, but are not limited to, certain types of attention,
      processing speed and memory. It is likely that individuals vary in terms of the
      efficiency of these underlying components, and in patterns of connectivity among
      these components, and that SL tasks differ from one another in how they draw on
      certain underlying components more than others. This theoretical framework is of
      value because it can assist in gaining a clearer understanding of how SL is
      linked with individual differences in complex mental activities such as language
      processing. Variability in language processing across individuals is of central
      concern to researchers interested in child development, including those
      interested in neurodevelopmental disorders where language can be affected such as
      autism spectrum disorders (ASD). This paper discusses the link between SL and
      individual differences in language processing in the context of age-related
      changes in SL during infancy and childhood, and whether SL is affected in ASD.
      Viewing SL as a multi-component ability may help to explain divergent findings
      from previous empirical research in these areas and guide the design of future
      studies.This article is part of the themed issue 'New frontiers for statistical
      learning in the cognitive sciences'.

PMID- 27872378
TI  - Abstraction and generalization in statistical learning: implications for the
      relationship between semantic types and episodic tokens.
AB  - Statistical approaches to emergent knowledge have tended to focus on the process
      by which experience of individual episodes accumulates into generalizable
      experience across episodes. However, there is a seemingly opposite, but equally
      critical, process that such experience affords: the process by which, from a
      space of types (e.g. onions-a semantic class that develops through exposure to
      individual episodes involving individual onions), we can perceive or create, on
      the-fly, a specific token (a specific onion, perhaps one that is chopped) in the
      absence of any prior perceptual experience with that specific token. This article
      reviews a selection of statistical learning studies that lead to the speculation
      that this process-the generation, on the basis of semantic memory, of a novel
      episodic representation-is itself an instance of a statistical, in fact
      associative, process. The article concludes that the same processes that enable
      statistical abstraction across individual episodes to form semantic memories also
      enable the generation, from those semantic memories, of representations that
      correspond to individual tokens, and of novel episodic facts about those tokens.
      Statistical learning is a window onto these deeper processes that underpin
      cognition.This article is part of the themed issue 'New frontiers for statistical
      learning in the cognitive sciences'.

PMID- 27872379
TI  - Predictors of Time to Union After Operative Fixation of Closed Ankle Fractures.
AB  - BACKGROUND: Ankle fractures are common and represent a significant burden to
      society. We aim to report the rate of union as determined by clinical and
      radiographic data, and to identify factors that predict time to union. METHODS: A
      cohort of 112 consecutive patients with isolated, closed, operative malleolar
      ankle fractures treated with open reduction and internal fixation was
      retrospectively reviewed for time to clinical union. Clinical union was defined
      based on radiographic and clinical parameters, and delayed union was defined by
      time to union >12 weeks. Injury characteristics, patient factors and treatment
      variables were recorded, and statistical techniques employed included the Chi
      square test, the Student's T-test, and multivariate linear regression modeling.
      RESULTS: Forty-two (37.5%) of patients who achieved union did so in less than 12
      weeks, and 69 (61.6%) of these patients demonstrated delayed union at a mean of
      16.7 weeks (range, 12.1-26.7 weeks), and the remaining patient required revision
      surgery. Factors associated with higher rates of delayed union or increased time
      to union included tobacco use, bimalleolar fixation, and high energy mechanism
      (all p<0.05). In regression analysis, statistically significant negative
      predictors of time to union were BMI, dislocation of the tibiotalar joint,
      external fixation for initial stabilization and delay of definitive management
      (all p<0.05). CONCLUSION: Patient characteristics, injury factors and treatment
      variables are predictive of time to union following open reduction and internal
      fixation of closed ankle fractures. These findings should assist with patient
      counseling, and help guide the provider when considering adjunctive therapies
      that promote bone healing. LEVELS OF EVIDENCE: Prognostic, Level IV: Case series.

PMID- 27872377
TI  - Towards a theory of individual differences in statistical learning.
AB  - In recent years, statistical learning (SL) research has seen a growing interest
      in tracking individual performance in SL tasks, mainly as a predictor of
      linguistic abilities. We review studies from this line of research and outline
      three presuppositions underlying the experimental approach they employ: (i) that
      SL is a unified theoretical construct; (ii) that current SL tasks are
      interchangeable, and equally valid for assessing SL ability; and (iii) that
      performance in the standard forced-choice test in the task is a good proxy of SL
      ability. We argue that these three critical presuppositions are subject to a
      number of theoretical and empirical issues. First, SL shows patterns of modality-
      and informational-specificity, suggesting that SL cannot be treated as a unified
      construct. Second, different SL tasks may tap into separate sub-components of SL
      that are not necessarily interchangeable. Third, the commonly used forced-choice
      tests in most SL tasks are subject to inherent limitations and confounds. As a
      first step, we offer a methodological approach that explicitly spells out a
      potential set of different SL dimensions, allowing for better transparency in
      choosing a specific SL task as a predictor of a given linguistic outcome. We then
      offer possible methodological solutions for better tracking and measuring SL
      ability. Taken together, these discussions provide a novel theoretical and
      methodological approach for assessing individual differences in SL, with clear
      testable predictions.This article is part of the themed issue 'New frontiers for
      statistical learning in the cognitive sciences'.

PMID- 27872380
TI  - Management of Distal Tibial Metaphyseal Bone Defects With an Intramedullary
      Nitinol Scaffold: A Novel Technique.
AB  - : Difficult problems that are faced when reconstructing severe pilon fractures
      include filling metaphyseal defects and supporting an impacted, multifragmented
      articular surface. Supplements to plate fixation currently available in a
      surgeon's armamentarium include cancellous bone autograft, structural bone
      allograft, demineralized bone matrix, and calcium-based cements. Cancellous
      autograft possesses limited inherent mechanical stability and is associated with
      graft site morbidity. Structural allografts incorporate inconsistently and are
      plagued by late resorption. Demineralized bone matrix also lacks inherent
      structural stability. Calcium phosphate cements are not rigidly fixed to bone
      unless fixation is applied from cortical bone or through a plate, which must be
      taken into consideration when planning fixation. The Conventus DRS (Conventus
      Orthopaedics, Maple Grove, MN) implant is an expandable nitinol scaffold that
      takes advantage of the elasticity and shape memory of nitinol alloy. Once
      deployed and locked, it serves as a stable intramedullary base for fragment
      specific periarticular fracture fixation, even in the face of metaphyseal bone
      loss. Two cases of successful implant use are presented. In both cases, the
      implant is used to fill a metaphyseal void and provide stable articular support
      to the distal tibial plafond. LEVELS OF EVIDENCE: Therapeutic Level V: Case
      Report, Expert Opinion.

PMID- 27872381
TI  - Results of the Gravity Stress Examination in the Normal Patient Population.
AB  - : In ankle fractures, the result of a gravity stress radiographic examination is
      clinically used to determine if a patient may need surgical intervention. The
      purpose of this study is to report the results of a gravity stress examination in
      the normal patient population. Fifty study participants were prospectively
      enrolled and complete ankle radiographs were obtained, including a
      nonweightbearing gravity stress examination. The mean medial clear space in the
      gravity stress view was 3.6 mm. This compared to a mean medial clear space of 3.3
      mm, and 3.1 mm in the anteroposterior and mortise views. These values were
      statistically significantly different from the gravity stress view (  P = .006
      and P < .001, respectively). There was no statistically significant difference
      between the talar tilt as measured on the anteroposterior and gravity stress
      radiographs (  P = .22). No participant had medial clear space widening with
      gravity stress to more than 5.2 mm or an increase in their widening by more than
      0.2 mm. In conclusion, this study helps guide surgeons by providing normative
      radiographic data for a gravity stress examination and supports the notion that
      measureable medial clear space widening or talar tilt on gravity stress
      examination represents an unstable injury. LEVELS OF EVIDENCE: Level II:
      Prospective.

PMID- 27872383
TI  - Stress appraisal, information processing strategies, and somatic symptoms: A
      longitudinal study with immigrants.
AB  - The study investigated threat versus challenge appraisals of acculturative
      stressors and their impact on the changes in psychological symptoms. It also
      examined information processing styles (informational, normative, and diffuse
      avoidant) as moderators of these relationships. A 6-month longitudinal study with
      two measuring points was conducted with a sample of immigrants. Threat appraisal
      was associated with more psychological symptoms, and challenge appraisal
      interacted with information processing styles to predict the changes in somatic
      symptoms. Analytical and exploratory informational styles enhanced the positive
      effects of challenge appraisal on psychological symptoms, whereas styles
      involving avoidance and normative orientation to one's home country dampened
      these positive effects.

PMID- 27872382
TI  - In utero exposure to LPS alters the postnatal acute-phase response in beef
      heifers.
AB  - The potential effect of prenatal LPS exposure on the postnatal acute phase
      response (APR) to an LPS challenge in heifers was determined. Pregnant crossbred
      cows were separated into prenatal immune stimulation (PIS) and saline groups
      (Control). From these treatments, heifer calves were identified at weaning to
      subsequently receive an exogenous LPS challenge. Sickness behavior scores (SBS)
      were recorded and blood samples were collected at 30-min intervals from -2 to 8 h
      and again at 24 h relative to the LPS challenge. There was a treatment * time
      interaction for the change in vaginal temperature (VT) such that the change in VT
      was greater in Control than PIS from 150 to 250 min, yet it was greater in PIS
      than Control from 355 to 440 min and from 570 to 1145 min. There was also a
      treatment * time interaction for SBS such that scores were greater in Control
      than PIS at 0.5 h, yet were greater in PIS than Control from 2.5 to 4 h post-LPS.
      There was a tendency for a treatment * time interaction for serum concentrations
      of IL-6, which were greater in PIS than Control heifers from 5.5 to 6 h and from
      7 to 8 h post-challenge. Thus, a single exposure to LPS during gestation can
      alter the postnatal APR to LPS in heifer calves.

PMID- 27872384
TI  - Dismantling prevention: Comparison of outcomes following media literacy and
      appearance comparison modules in a randomised controlled trial.
AB  - A dismantling study of body dissatisfaction prevention was conducted. Adolescent
      girls ( N = 260) were randomly allocated to a media literacy (Happy Being Me -
      Media Literacy) or appearance comparison (Happy Being Me - Appearance Comparison)
      intervention or healthy eating behaviour control (Happy Being Me - Healthy Eating
      Behaviour) condition. In the Happy Being Me - Appearance Comparison condition,
      improvements from baseline to post-programme and follow-up for upward appearance
      comparison and fear of negative appearance evaluation were observed. In the Happy
      Being Me - Media Literacy condition, improvements were observed from baseline to
      post-programme for upward appearance comparison and realism scepticism. Findings
      were similar in a high-risk subsample and overall are moderately supportive of
      appearance comparison-based interventions, but less supportive of a stand-alone
      media literacy intervention.

PMID- 27872386
TI  - Transformational leadership in primary care: Clinicians' patterned approaches to
      care predict patient satisfaction and health expectations.
AB  - Clinicians face the complex challenge of motivating their patients to achieve
      optimal health while also ensuring their satisfaction. Inspired by
      transformational leadership theory, we proposed that clinicians' motivational
      behaviors can be organized into three patient care styles (transformational,
      transactional, and passive-avoidant) and that these styles differentially predict
      patient health outcomes. In two studies using patient-reported data and observer
      ratings, we found that transformational patient care style positively predicted
      patients' satisfaction and health expectations above and beyond transactional and
      passive-avoidant patient care style. These findings provide initial support for
      the patient care style approach and suggest novel directions for the study of
      clinicians' motivational behaviors.

PMID- 27872385
TI  - Development and validation of the 'Echelle de Motivation envers l'Activite
      Physique en contexte de Sante': A motivation scale towards health-oriented
      physical activity in French.
AB  - This article presents the validation of the 'Echelle de Motivation envers
      l'Activite Physique en contexte de Sante' including the six forms of motivation
      underlined by self-determination theory. Study 1 underlines the content validity
      of a pool of 30 items ( N = 20). Study 2 supports the six-factor structure
      validity of the 18-item Echelle de Motivation envers l'Activite Physique en
      contexte de Sante ( N = 309). Study 3 ( N = 191) confirms structure validity, as
      well as concurrent validity and 2-week temporal reliability. The Echelle de
      Motivation envers l'Activite Physique en contexte de Sante can be considered as a
      valid and reliable tool to use in prevention or rehabilitation contexts.

PMID- 27872387
TI  - Associations of perceived risk and cancer worry for colorectal cancer with
      screening behaviour.
AB  - We investigated the associations of perceived risk and cancer worry with
      colorectal cancer screening by the faecal occult blood test, colonoscopy or both.
      This study was based on the 2013 Korean National Cancer Screening Survey,
      including 2154 randomly selected, cancer-free and over 50-year-old adults.
      Individuals with higher cancer worry were 1.53 times more likely to undergo
      colorectal cancer screening, influenced by emotional reaction; individuals with
      greater perceived risk were 1.61 times more, affected by subjective awareness.
      However, cancer worry was only associated with the faecal occult blood test.
      Better understanding of cancer worry and perceived risk on screening behaviours
      may help to increase colorectal cancer screening rates.

PMID- 27872388
TI  - Psychometric properties of the Chinese version of the Affective Style
      Questionnaire and its role as a moderator of the relationship between stress and
      negative affect.
AB  - The Affective Style Questionnaire is a self-report instrument for assessing
      affective style. Study 1 investigated the psychometric properties of the Chinese
      Affective Style Questionnaire in a sample of 459 Chinese participants. The
      confirmatory factor analysis supported a three-factor structure. Study 1
      indicated that the Chinese Affective Style Questionnaire can be used as a simple,
      reliable, and valid scale for measuring individual differences in affective
      style. Study 2 examined the moderating role of different affective styles in the
      relationship between stress and negative affect. Concealing and tolerating
      moderated the relationship between stress and anxiety, and adjusting moderated
      the relationship between stress and depression.

PMID- 27872389
TI  - Promoting fruit and vegetable intake in childbearing age women at risk for
      gestational diabetes mellitus: A randomised controlled trial.
AB  - This randomised controlled trial verified the efficacy of an implementation
      intentions intervention ( n = 24) to promote fruit and vegetable consumption
      among childbearing age women at risk for gestational diabetes mellitus against a
      control condition based on the question-behaviour effect ( n = 26). There was
      only a significant time effect ( F(2,85) = 5.69, p = 0.0048). Both groups
      increased their vegetable consumption compared to baseline at 3 months ( p =
      0.0022) and 6 months ( p = 0.0042). There were no significant effects on weight,
      waist circumference and blood glucose levels. Implementation intentions and the
      question-behaviour effect appear to be effective behaviour change techniques to
      promote vegetable intake among this high-risk population.

PMID- 27872390
TI  - Classifying diabetes-burden: A factor analysis of the Problem Areas in Diabetes
      Scale.
AB  - This study sought to identify salient factors associated with the Problem Areas
      in Diabetes Scale to facilitate improved assessment and treatment of diabetes
      related burden. Exploratory factor analysis assessed the factor structure of the
      Problem Areas in Diabetes Scale among 224 Veterans with uncontrolled type 2
      diabetes and depressive symptoms. A four-factor solution of emotional, diabetes
      management, treatment, and social support burden subscales was extracted. These
      factors represent clinically relevant components of diabetes burden that include
      but go beyond symptoms of depression. The Problem Areas in Diabetes subscales may
      expand assessments for depression and improve medical and behavioral health
      interventions for patients with diabetes.

PMID- 27872391
TI  - The Role of School Health Services in Addressing the Needs of Students With
      Chronic Health Conditions.
AB  - Children and adolescents in the United States spend many hours in school.
      Students with chronic health conditions (CHCs) may face lower academic
      achievement, increased disability, fewer job opportunities, and limited community
      interactions as they enter adulthood. School health services provide safe and
      effective management of CHCs, often for students with limited access to health
      care. A systematic review to assess the role of school health services in
      addressing CHCs among students in Grades K-12 was completed using primary, peer
      reviewed literature published from 2000 to 2015, on selected conditions: asthma,
      food allergies, diabetes, seizure disorders, and poor oral health. Thirty-nine
      articles met the inclusion criteria and results were synthesized; however, 38
      were on asthma. Direct access to school nursing and other health services, as
      well as disease-specific education, improved health and academic outcomes among
      students with CHCs. Future research needs to include standardized definitions and
      data collection methods for students with CHCs.

PMID- 27872392
TI  - A Scoping Review of Self-Report Measures of Aggression and Bullying for Use With
      Preadolescent Children.
AB  - Bullying in schools is a major health concern throughout the world, contributing
      to poor educational and mental health outcomes. School nurses are well placed to
      facilitate the implementation and evaluation of bullying prevention strategies.
      To evaluate the effect of such strategies, it is necessary to measure children's
      behavior over time. This scoping review of instruments that measure the self
      report of aggressive behavior and bullying by children will inform the evaluation
      of bullying interventions. This review aimed to identify validated instruments
      that measure aggression and bullying among preadolescent children (age 8-12). The
      review was part of a larger study that sought to differentiate bullying from
      aggressive behavior by measuring the self-report of power imbalance between the
      aggressor and the child being bullied. The measurement of power imbalance was
      therefore a key aspect of the scoping review.

PMID- 27872393
TI  - Moralization Through Moral Shock: Exploring Emotional Antecedents to Moral
      Conviction.
AB  - The current research tested whether exposure to disgusting images increases moral
      conviction and whether this happens in the presence of incidental disgust cues
      versus disgust cues relevant to the target of moralization. Across two studies,
      we exposed participants to one of the four sets of disgusting versus control
      images to test the moralization of abortion attitudes: pictures of aborted
      fetuses, animal abuse, non-harm related disgusting images, harm related
      disgusting images, or neutral pictures, at either sub- or supraliminal levels of
      awareness. Moral conviction about abortion increased (compared with control) only
      for participants exposed to abortion-related images at speeds slow enough to
      allow conscious awareness. Study 2 replicated this finding, and found that the
      relationship between attitudinally relevant disgust and moral conviction was
      mediated by disgust, and not anger or harm appraisals. Findings are discussed in
      terms of their relevance for intuitionist theories of morality and moral theories
      that emphasize harm.

PMID- 27872394
TI  - Women's Fertility Status Alters Other Women's Jealousy and Mate Guarding.
AB  - Across three studies, we tested the hypothesis that women exhibit greater
      jealousy and mate guarding toward women who are in the high (vs. low) fertility
      phase of their cycle. Women who imagined their partner with a woman pictured at
      high fertility reported more jealousy than women who imagined their partner with
      a woman pictured at low fertility (Studies 1 and 2). A meta-analysis across
      studies manipulating fertility status of the pictured woman found a significant
      effect of fertility status on both jealousy and mate guarding. Women with
      attractive partners viewed fertile-phase women as less trustworthy, which led to
      increased mate guarding (Study 2). In Study 3, the closer women were to peak
      fertility, the more instances they reported of other women acting jealously and
      mate guarding toward them. These studies provide evidence that women selectively
      exhibit jealousy and mate guarding toward women who are near peak fertility.

PMID- 27872395
TI  - Strangers With Benefits: Attraction to Outgroup Men Increases as Fertility
      Increases Across the Menstrual Cycle.
AB  - Research typically reveals that outgroups are regarded with disinterest at best
      and hatred and enmity at worst. Working from an evolutionary framework, we
      identify a unique pattern of outgroup attraction. The small-group lifestyle of
      pre-human ancestors plausibly limited access to genetically diverse mates.
      Ancestral females may have solved the inbreeding dilemma while balancing parental
      investment pressures by mating with outgroup males either via converting to an
      outgroup or cuckolding the ingroup. A vestige of those mating strategies might
      manifest in human women as a cyclic pattern of attraction across the menstrual
      cycle, such that attraction to outgroup men increases as fertility increases
      across the cycle. Two studies, one using a longitudinal method and the other an
      experimental method, evidenced the hypothesized linear relationship between
      attraction to outgroup men and fertility in naturally cycling women.

PMID- 27872397
TI  - Pulmonary Mycobacterium marinum infection: 'fish tank granuloma' of the lung.
AB  - A 65-year-old man presented with a six-month history of lethargy, weight loss and
      dry cough. He had a background of mild chronic obstructive pulmonary disease.
      Chest radiograph showed new right upper lobe cavitary opacification. Sputum
      cultures were acid-fast bacilli smear positive and yielded Mycobacterium marinum 
      a non-tuberculous mycobacterium (NTM) often found in aquatic environments and
      rarely associated with respiratory disease. The suspected source was silent
      aspiration of contaminated water, likely due to his initiating the siphon of his
      fish-tank by mouth. He completed a one-year course of rifampicin, ethambutol and
      clarithromycin, with negative repeat sputum mycobacteria cultures and
      radiological improvement. This case report demonstrates a successful approach to
      investigation and further management of Mycobacterium marinum pulmonary disease -
      a rare condition, particularly in immunocompetent individuals, with limited
      treatment guidelines.

PMID- 27872398
TI  - Five-year study of unidentified/unclaimed and unknown deaths brought for
      medicolegal autopsy at Premier Hospital in New Delhi, India.
AB  - Delhi is the second largest city of the world both in terms of population and
      area, as well as being the capital of India. Every year, thousands of people from
      different states throng to the capital in search of a job in order to earn a
      living. When these people die and their bodies are found without any identifying
      documentation, it is very difficult for the police to establish their identities.
      These bodies are labelled as unidentified/unclaimed or unknown, and are sent for
      usually sent for medicolegal autopsy. Invariably, skeletonised bodies are also
      recovered, which are also subjected to medicolegal autopsy. Female foeticide is
      another social problem, and whenever such foetuses are disposed of illegally,
      they are also grouped under this category and brought for medicolegal autopsy. We
      undertook a five-year retrospective analysis (for the period 2010-2014) of all
      such cases brought for medicolegal autopsy at our centre, which caters only for
      the south and south-east districts of Delhi. A total of 7964 cases were brought
      for medicolegal autopsy, of which unknown cases accounted for about 16%. About 25
      30 foetuses and skeletonised bodies were brought each year that was studied. The
      manner of death was certified as natural in about 71% of cases, with predominant
      pathology in the lungs. There was a clear predominance of males over females,
      with the 31- to 50-year age group accounting for half of all cases. There was an
      increase in the number of deaths during months of extreme temperatures. The
      average time between the recovery of a body by the police and the post-mortem was
      about seven days. These findings raise many questions, including the failure of
      governmental policies, police investigating agencies and social menace. The
      creation of a national missing-persons database as well as a DNA databank is
      needed to aid in the identification of unidentified/unclaimed and unknown bodies.

PMID- 27872396
TI  - Comparison of estimates of body fat content in childhood-onset systemic lupus
      erythematosus.
AB  - Objective We aimed to compare estimates of body fat content with respect to their
      ability to predict the percentage of body fat, confirmed by dual-energy X-ray
      absorptiometry scans in childhood-onset systemic lupus erythematosus. Methods We
      included 64 consecutive childhood-onset systemic lupus erythematosus patients and
      64 healthy age and sex-matched controls in a cross-sectional study.
      Anthropometric data, body mass index and body adiposity index were calculated for
      all subjects. Childhood-onset systemic lupus erythematosus patients were further
      assessed for clinical and laboratory childhood-onset systemic lupus erythematosus
      manifestations and fat mass, lean mass and percentage of body fat evaluated by
      dual-energy X-ray absorptiometry. Results Elevated waist/hip ratio was observed
      in childhood-onset systemic lupus erythematosus patients when compared to
      controls ( p < 0.001). We did not find differences between body mass index and
      body adiposity index classification in childhood-onset systemic lupus
      erythematosus patients and controls. Using dual-energy X-ray absorptiometry as
      gold standard we observed that all indirect estimates of body fat were correlated
      with whole body fat mass. We observed a correlation between height and cumulative
      corticosteroid dose adjusted by weight ( r = 0.429, p = 0.005) in childhood-onset
      systemic lupus erythematosus. On whole body analysis we observed a correlation
      between lean mass and ACR Damage Index scores ( r = -0.395; p = 0.019);
      percentage of body fat and adjusted Systemic Lupus Erythematosus Disease Activity
      Index ( r = 0.402; p = 0.008), disease duration ( r = -0.370; p = 0.012). On
      trunk analysis we observed a correlation between lean mass and ACR Damage Index (
      r = -0.319; p = 0.042); percentage of body fat with adjusted Systemic Lupus
      Erythematosus Disease Activity Index ( r = 0.402; p = 0.005), disease duration (
      r = -0.408; p = 0.005). Conclusions This is the first study analyzing body
      adiposity index in childhood-onset systemic lupus erythematosus patients. We
      observed that all indirect estimates of body fat were correlated with whole body
      fat mass. This study shows that we should not replace body mass index by body
      adiposity index to evaluating fat levels in childhood-onset systemic lupus
      erythematosus. In consideration of the importance of overweight classification in
      cardiovascular diseases, any direct estimates of body fat can be used in an
      attempt to improve the prognosis of patients. Note We believe that we have
      presented evidence of body adiposity index accuracy in childhood-onset systemic
      lupus erythematosus patients but further research on the generalizability of body
      adiposity index to other patient groups needs to be done.

PMID- 27872399
TI  - Health and Rural Context Among Victims of Partner Abuse: Does Justice Matter?
AB  - Research typically compartmentalizes health and justice as separate areas of
      study. However, the current health literature on inequality suggests the two
      concepts are overlapping. For victims of partner violence, procedural justice
      (defined in this article as access to protective orders and enforcement of
      protective orders) potentially provides a step toward improved health and well
      being by improving safety. There has been limited research examining these
      factors in rural compared with urban areas. This study examines the impact of
      procedural justice on health and well-being through interviews with rural and
      urban women 6 months prior to, and 6 months after, obtaining a protective order.
      Consistent with other literature, rural women who were victims of partner
      violence reported worse health, higher stress, and higher Stress-Related
      Consequences Scale scores compared with urban women. Women's reported health
      consequences were related to the interaction of perceived ineffectiveness of the
      protective orders and their rural/urban environment. Thus, the perceived
      effectiveness of procedural justice may play an important role in alleviating
      victims' safety, health, and well-being, all of which are components of
      contemporary views of justice.

PMID- 27872400
TI  - Creative Defiance.
AB  - Throughout his work, Chaz Maviyane-Davies has used images and ideas to cut
      through complacency and apathy while trying to raise social consciousness. The
      issues addressed in his work have included social discrimination, human rights,
      health, and the environment. Creating an expressive alternate vision in a
      pervading regressive body politic has never been easy and therein lies the
      challenge he calls "Creative Defiance." The article is from a presentation which
      was made at the University of Massachusetts Lowell in 2016.

PMID- 27872401
TI  - Criminality and Asbestos in Industry.
AB  - Criminal prosecutions of individuals in the asbestos industry are reviewed,
      particularly the case of asbestos owner-executive Stephan Schmidheiny. Italian
      courts sentenced Schmidheiny to sixteen to eighteen years in jail for creating an
      environmental disaster causing three thousand deaths. The convictions were
      overturned on a technicality, and a murder case against Schmidheiny has started.
      His firm, Eternit, made asbestos-cement building products in many countries.
      Schmidheiny directed a cover-up that the Italian Court of Appeal blamed for
      delaying the ban of asbestos in Italy by ten years. Today, the asbestos industry
      is a criminal industry, profiting only by minimizing its costs for the prevention
      and compensation of occupational and environmental illness. The asbestos industry
      should only be consulted by governments for the purpose of closing it and dealing
      with the legacy of in-place asbestos.

PMID- 27872402
TI  - Effect of Training Exercise on Urinary Brain-derived Neurotrophic Factor Levels
      and Cognitive Performances in Overweight and Obese Subjects.
AB  - Exercise-mediated, brain-derived neurotrophic factor induction benefits health
      and cognitive functions. The multifaceted interplay between physical activity,
      urinary brain-derived neurotrophic factor levels and cognitive functioning has
      been largely neglected in previous literature. In this pilot study, two bouts of
      training exercise (65% and 70% of heart rate reserve) influenced urinary brain
      derived neurotrophic factor levels and cognitive performances in 12 overweight
      and obese participants. Percent heart rate reserve, expenditure energy, brain
      derived neurotrophic factor urinary levels and cognitive performances were
      measured before and after the exercise. No significant variations in energy
      expenditure were observed, while differences of heart rate reserve between two
      groups were maintained. Both bouts of training exercise induced a similar
      reduction in urinary brain-derived neurotrophic factor levels. Only visuo-spatial
      working memory capacity at 65% of heart rate reserve showed a significant
      increase. These findings indicate a consistent effect of training exercise on
      urinary brain-derived neurotrophic factor levels and cognitive factors in
      overweight and obese participants.

PMID- 27872403
TI  - Biomechanical Analysis of Weighted-Ball Exercises for Baseball Pitchers.
AB  - BACKGROUND: Weighted-ball throwing programs are commonly used in training
      baseball pitchers to increase ball velocity. The purpose of this study was to
      compare kinematics and kinetics among weighted-ball exercises with values from
      standard pitching (ie, pitching standard 5-oz baseballs from a mound).
      HYPOTHESIS: Ball and arm velocities would be greater with lighter balls and joint
      kinetics would be greater with heavier balls. STUDY DESIGN: Controlled laboratory
      study. METHODS: Twenty-five high school and collegiate baseball pitchers
      experienced with weighted-ball throwing were tested with an automated motion
      capture system. Each participant performed 3 trials of 10 different exercises:
      pitching 4-, 5-, 6-, and 7-oz baseballs from a mound; flat-ground crow hop throws
      with 4-, 5-, 6-, and 7-oz baseballs; and flat-ground hold exercises with 14- and
      32-oz balls. Twenty-six biomechanical parameters were computed for each trial.
      Data among the 10 exercises were compared with repeated measures analysis of
      variance and post hoc paired t tests against the standard pitching data. RESULTS:
      Ball velocity increased as ball mass decreased. There were no differences in arm
      and trunk velocities between throwing a standard baseball and an underweight
      baseball (4 oz), while arm and trunk velocities steadily decreased as ball weight
      increased from 5 to 32 oz. Compared with values pitching from a mound, velocities
      of the pelvis, shoulder, and ball were increased for flat-ground throws. In
      general, as ball mass increased arm torques and forces decreased; the exception
      was elbow flexion torque, which was significantly greater for the flat-ground
      holds. There were significant differences in body positions when pitching on the
      mound, flat-ground throws, and holds. CONCLUSIONS: While ball velocity was
      greatest throwing underweight baseballs, results from the study did not support
      the rest of the hypothesis. Kinematics and kinetics were similar between
      underweight and standard baseballs, while overweight balls correlated with
      decreased arm forces, torques, and velocities. Increased ball velocity and joint
      velocities were produced with crow hop throws, likely because of running forward
      while throwing. CLINICAL RELEVANCE: As pitching slightly underweight and
      overweight baseballs produces variations in kinematics without increased arm
      kinetics, these exercises seem reasonable for training pitchers. As flat-ground
      throwing produces increased shoulder internal rotation velocity and elbow varus
      torque, these exercises may be beneficial but may also be stressful and risky.
      Flat-ground holds with heavy balls should not be viewed as enhancing pitching
      biomechanics, but rather as hybrid exercises between throwing and resistance
      training.

PMID- 27872405
TI  - When Wife-Beating Is Not Necessarily Abuse: A Feminist and Cross-Cultural
      Analysis of the Concept of Abuse as Expressed by Tibetan Survivors of Domestic
      Violence.
AB  - This article describes the views of Tibetan women who have experienced physical
      violence from male intimate partners. How they conceptualise abuse, their views
      on acceptable versus unacceptable hitting, and the acts besides hitting which
      they felt to be unacceptable or abusive, are explored. Views of survivors'
      relatives/friends and men who have hit their wives are also included. Western
      based domestic violence theory is shown to be incommensurate with abuse in
      particular socio-cultural settings. As feminist scholars emphasize listening
      deeply to voices of women in the global South, this article demonstrates how such
      listening might be undertaken when the views expressed by women diverge from
      feminism.

PMID- 27872404
TI  - Unique Cellular Lineage Composition of the First Gland of the Mouse Gastric
      Corpus.
AB  - The glandular stomach has two major zones: the acid secreting corpus and the
      gastrin cell-containing antrum. Nevertheless, a single gland lies at the
      transition between the forestomach and corpus in the mouse stomach. We have
      sought to define the lineages that make up this gland unit at the squamocolumnar
      junction. The first gland in mice showed a notable absence of characteristic
      corpus lineages, including parietal cells and chief cells. In contrast, the gland
      showed strong staining of Griffonia simplicifolia-II (GSII)-lectin-positive
      mucous cells at the bases of glands, which were also positive for CD44 variant 9
      and Clusterin. Prominent numbers of doublecortin-like kinase 1 (DCLK1) positive
      tuft cells were present in the first gland. The first gland contained Lgr5
      expressing putative progenitor cells, and a large proportion of the cells were
      positive for Sox2. The cells of the first gland stained strongly for MUC4 and
      EpCAM, but both were absent in the normal corpus mucosa. The present studies
      indicate that the first gland in the corpus represents a unique anatomic entity.
      The presence of a concentration of progenitor cells and sensory tuft cells in
      this gland suggests that it may represent a source of reserve reparative cells
      for adapting to severe mucosal damage.

PMID- 27872406
TI  - Life cycle assessment of potential municipal solid waste management strategies
      for Mumbai, India.
AB  - Dumping of municipal solid waste into uncontrolled dumpsites is the most common
      method of waste disposal in most cities of India. These dumpsites are posing a
      serious challenge to environmental quality and sustainable development. Mumbai,
      which generates over 9000 t of municipal solid waste daily, also disposes of most
      of its waste in open dumps. It is important to analyse the impact of municipal
      solid waste disposal today and what would be the impact under integrated waste
      management schemes. In this study, life cycle assessment methodology was used to
      determine the impact of municipal solid waste management under different
      scenarios. Six different scenarios were developed as alternatives to the current
      practice of open dumping and partially bioreactor landfilling. The scenarios
      include landfill with biogas collection, incineration and different combinations
      of recycling, landfill, composting, anaerobic digestion and incineration. Global
      warming, acidification, eutrophication and human toxicity were assessed as
      environmental impact categories. The sensitivity analysis shows that if the
      recycling rate is increased from 10% to 90%, the environmental impacts as
      compared with present scenario would reduce from 998.43 kg CO2 eq t-1 of
      municipal solid waste, 0.124 kg SO2 eq t-1, 0.46 kg PO4-3 eq t-1, 0.44 kg 1,4-DB
      eq t-1 to 892.34 kg CO2 eq t-1, 0.121 kg SO2 eq t-1, 0.36 kg PO4-3 eq t-1, 0.40
      kg 1,4-DB eq t-1, respectively. An integrated municipal solid waste management
      approach with a mix of recycling, composting, anaerobic digestion and landfill
      had the lowest overall environmental impact. The technologies, such as
      incineration, would reduce the global warming emission because of the highest
      avoided emissions, however, human toxicity would increase.

PMID- 27872408
TI  - Active Expiration and the Measurement of Central Venous Pressure.
AB  - PURPOSE: To obtain a point prevalence estimate of alterations in central venous
      pressure (CVP) produced by active expiration in a consecutive series of intensive
      care patients. METHODS: We evaluated CVP tracings taken by the nurses at their
      morning shift change in a consecutive series of 60 cardiac surgery and 59
      noncardiac surgery patients. We also assessed change in values due to the change
      in transducer level. Three physicians and a nurse instructor independently
      reviewed the tracings and determined whether there was evidence of forced
      expiration and whether it was type A, defined by decreasing CVP during
      expiration, or type B, defined by increasing CVP during expiration. RESULTS:
      Agreement for CVP value was 96% between a physician and a bedside nurse. Twenty
      nine percent of participants had active expiration, evenly distributed between A
      and B types. Active expiration was not related to the type of surgery, use of
      bronchodilators, and the presence of chronic obstructive lung disease or
      abdominal distention. Active expiration was more common in nonventilated patients
      and patients not receiving vasopressor drugs, suggesting they were more awake.
      CONCLUSION: Active expiration is common in critically ill patients. Failure to
      recognize it can result in important errors in the estimation of CVP and other
      hemodynamic measurements.

PMID- 27872407
TI  - Fatigue, Work Schedules, and Perceived Performance in Bedside Care Nurses.
AB  - Hospital nurses are expected to maintain optimal work performance; yet, fatigue
      can threaten safe practice and result in unfavorable patient outcomes. This
      descriptive cross-sectional study explored the association between fatigue, work
      schedules, and perceived work performance among nurses. The study sample included
      77 bedside nurses who were mostly female, single, and between 20 and 29 years of
      age. The majority worked 8-hour shifts and overtime. Nurses who worked during off
      days reported significantly higher chronic fatigue compared with those nurses who
      took time off. Nurses who reported feeling refreshed after sleep had
      significantly less chronic and acute fatigue and more intershift recovery. Nurses
      with acute and chronic fatigue perceived poorer physical performance. Also,
      nurses who reported chronic fatigue perceived they were less alert and less able
      to concentrate when providing patient care. Less effective communication was also
      associated with acute and chronic fatigue. In conclusion, fatigue has safety
      implications for nurses' practice that should be monitored by nursing management.

PMID- 27872409
TI  - Complexity Analysis of Decision-Making in the Critically Ill.
AB  - RATIONALE: Despite multiple trials of interventions to improve end-of-life care
      of the critically ill, there is a persistent lack of understanding of factors
      associated with barriers to decision-making at the end of life. OBJECTIVE: To
      apply the principles of complexity science in examining the extent to which
      transitions to end-of-life care can be predicted by physician, family, or patient
      characteristics; outcome expectations; and the evaluation of treatment
      effectiveness. METHODS: A descriptive, longitudinal study was conducted in 3
      adult intensive care units (ICUs). Two hundred sixty-four family surrogates of
      patients lacking decisional capacity and the physicians caring for the patients
      were interviewed every 5 days until ICU discharge or patient death. MEASUREMENTS:
      Characteristics of patients, physicians, and family members; values and
      preferences of physicians and family; and evaluation of treatment effectiveness,
      expectations for patient outcomes, and relative priorities in treatment (comfort
      vs survival). The primary outcome, focus of care, was categorized as (1)
      maintaining a survival orientation (no treatment limitations), (2) transitioning
      to a stronger palliative focus (eg, some treatment limitations), or (3)
      transitioning to an explicit end-of-life, comfort-oriented care plan. MAIN
      RESULTS: Physician expectations for survival and future cognitive status were the
      only variables consistently and significantly related to the focus of care.
      Neither physician or family evaluations of treatment effectiveness nor what was
      most important to physicians or family members was influential. CONCLUSION: Lack
      of influence of family and physician views, in comparison to the consistent
      effect of survival probabilities, suggests barriers to incorporation of
      individual values in treatment decisions.

PMID- 27872410
TI  - Risk of Mortality of Catheter-Related Bloodstream Infections Caused by
      Acinetobacter Species: Is Early Removal of the Catheters Associated With a Better
      Survival Outcome?
AB  - PURPOSE: Bloodstream infections (BSIs) caused by Acinetobacter species have been
      extensively reported, however, which majorly focused on respiratory tract
      infections. The risk of mortality and the effect of early catheter removal on
      survival in catheter-related BSIs (CRBSIs) caused by Acinetobacter spp. remain
      unclear. This study aims to investigate that. METHODS: This is a retrospective
      multicentric study conducted in Taiwan from 2012 to 2014. Patients with at least
      1 positive blood culture and catheter culture for the same Acinetobacter spp.,
      showing symptoms and signs of CRBSIs, were included (n = 119). Risk factors for
      30-day mortality were analyzed using a logistic regression model. The
      characteristics of patients with early catheter removal (within 48 hours after
      CRBSIs) were compared to those without removal matching for age, sex, and disease
      severity. RESULTS: There were no differences in 30-day mortality with regard to
      causative Acinetobacter spp., catheter type, site, and appropriateness of
      antimicrobial therapy. Patients with higher Acute Physiologic and Chronic Health
      Evaluation (APACHE) II scores (odds ratio [OR]: 1.12; 95% confidence interval
      [CI]: 1.02-1.23; P = .014), shock (OR: 6.43; 95% CI: 1.28-32.33; P = .024), and
      longer hospitalization before CRBSIs (OR: 1.04; 95% CI: 1.00-1.08; P = .027) had
      a significantly higher 30-day mortality rate. Early removal of catheters after
      CRBSIs was not associated with better survival benefits. CONCLUSION: Higher
      disease severity (APACHE II score), shock, and longer hospitalization before
      bacteremia were independently associated with a higher 30-day mortality in CRBSIs
      caused by Acinetobacter spp. In previous published guidelines, infected catheters
      were suggested to be removed in CRBSIs caused by gram-negative bacilli. Even
      though early removal of catheters did not associate with a better survival
      outcome in current results, it should be judiciously evaluated according to the
      clinical conditions and risks individually. For better elucidation of these
      issues, further well-controlled prospective study may be warranted.

PMID- 27872411
TI  - Osteoporosis in Pediatric Liver Transplantation.
AB  - Liver transplantation provides an important, often life-saving treatment for end
      stage liver disease. Osteoporosis post-liver transplantation has been described
      in adults; however, this has not been described in the pediatric population to
      date. We present a case of a 13-year-old female patient who underwent an
      orthotopic liver transplant for cryptogenic liver cirrhosis. Her
      immunosuppressants were tacrolimus and prednisone. Four months posttransplant,
      she started complaining of bilateral lower limb pain and limping while walking,
      progressing to a point where she was almost immobile. Magnetic resonance
      imagining of the pelvis showed bilateral avascular necrosis involving the weight
      bearing surfaces of both femoral heads, in addition to the extensive edema
      involving both hip joints. Bone mineral densitometry was below normal for her age
      at the hip and forearm. She was started on high-dose calcium and vitamin D
      supplement, as well as zoledronic acid with a remarkable symptomatic and
      functional improvement.

PMID- 27872412
TI  - Estimation of Viscoelastic Properties of Cells Using Acoustic Tweezing Cytometry.
AB  - OBJECTIVES: Recently developed acoustic tweezing cytometry uses ultrasound
      responsive targeted microbubbles for biomechanical stimulation of live cells at
      the subcellular level. The purpose of this research was to estimate the
      viscoelastic characteristics of cells from the displacements of cell-bound
      microbubbles in response to ultrasound pulses on acoustic tweezing cytometry.
      METHODS: Microbubbles were bound to NIH/3T3 fibroblasts and ATDC5 cells through
      an integrin-cytoskeleton linkage. The evolution of microbubble behaviors under
      irradiation by ultrasound pulses was captured by a high-speed camera and tracked
      by a customized algorithm. The total damping constant, stiffness, and rigidity of
      the cells were estimated by fitting the measured temporal displacement profiles
      to a Kelvin-Voigt-based model. RESULTS: The mean maximum displacement of the
      microbubbles attached to NIH/3T3 fibroblasts was much greater than that for ATDC5
      cells. The mean fitted damping constant and stiffness +/- SD for ATDC5 cells were
      28.16 +/- 7.08 mg/s and 0.5041 +/- 0.1381 mN/m, respectively, and the values for
      NIH/3T3 fibroblasts were 13.12 +/- 4.23 mg/s and 0.2591 +/- 0.0715 mN/m. The
      rigidity for ATDC5 cells was 331.46 +/- 106.50 MPa, whereas that for NIH/3T3
      fibroblasts was 117.92 +/- 34.83 MPa. CONCLUSIONS: The Arg-Gly-Asp-integrin
      cytoskeleton system of NIH/3T3 fibroblasts appears to be softer than that of
      ATDC5 cells. The rigidity of ATDC5 cells was significantly greater than that of
      NIH/3T3 fibroblasts at the 95% confidence level. This strategy provides a novel
      way to determine the viscoelastic properties of the live cells.

PMID- 27872414
TI  - Effect of Low-Dose Aspirin on Midluteal Phase Uterine Artery Blood Flow in
      Patients With Recurrent Pregnancy Loss.
AB  - OBJECTIVES: The purpose of this study was to evaluate differences in uterine
      artery blood flow parameters and pregnancy outcomes, if any. An investigation was
      conducted to determine the effects of low-dose aspirin on uterine artery blood
      flow indices in patients with recurrent pregnancy loss. METHODS: This
      observational study included 353 Chinese women with a history of recurrent
      pregnancy loss and 85 women without a history of recurrent pregnancy loss
      (control group) from Ren Ji Hospital. All patients were scanned transvaginally
      with transvaginal Doppler sonography 6 to 8 days after ovulation to measure the
      pulsatility index (PI), resistive index (RI), and systolic-to-diastolic ratio
      (S/D) of the left and right main uterine arteries. Low-dose aspirin at a dose of
      50 mg/d was administered orally in patients with recurrent pregnancy loss for 2
      months, and the blood flow indices were measured subsequently. The Student t test
      was used for analysis of the results, P < .05 was considered significant.
      RESULTS: The mean PI and S/D of the uterine arteries in the recurrent pregnancy
      loss group were significantly higher than in the control group. Although not
      statistically significant, the RI was higher in the recurrent pregnancy loss
      group than the control group. Moreover, the PI and S/D increased as the number of
      pregnancy losses increased. Significant enhancements of the PI and S/D were
      observed in patients with 4 or more consecutive abortions. After low-dose aspirin
      supplementation, patients with recurrent pregnancy loss showed a highly
      significant reduction in the PI and S/D. CONCLUSIONS: Uterine blood flow
      decreased during the luteal phase in patients with recurrent pregnancy loss. Low
      dose aspirin induced a reversible increase in uterine blood flow and may be of
      therapeutic value.

PMID- 27872413
TI  - Is There Any Difference Between Seminomas and Nonseminomatous Germ Cell Tumors on
      Shear Wave Elastography? A Preliminary Study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the ability of shear wave
      elastography (SWE) to differentiate seminomas from nonseminomatous germ cell
      tumors. METHODS: Approval for this retrospective study was obtained from the
      local Ethics Committee of Istanbul University Cerrahpasa Medical School. Fifteen
      patients with malignant testicular lesions were examined by grayscale sonography,
      color or power Doppler sonography, and SWE between February 2011 and October
      2015. The size of each lesion, Doppler signal parameters, echogenicity, presence
      of microlithiasis, unifocality or multifocality, and histopathologic findings
      were the main factors evaluated. RESULTS: The mean age of the patients was 33
      years (range, 25-55 years). There were no differences between seminomas and
      nonseminomatous germ cell tumors in terms of Doppler signals, echogenicity,
      microlithiasis, or focality. Only the homogeneous and heterogeneous echogenicity
      patterns differed significantly. However, a significant difference was evident in
      SWE-derived quantitative data. CONCLUSIONS: Seminomas and nonseminomatous germ
      cell tumors do not differ significantly on grayscale or Doppler sonography,
      except in terms of homogeneity. However, SWE seems to differentiate seminomas
      from nonseminomatous germ cell tumors.

PMID- 27872415
TI  - Training Performance in Diagnosis of Congenital Uterine Anomalies With 3
      Dimensional Sonography: A Learning Curve Cumulative Summation Analysis.
AB  - OBJECTIVES: We evaluated learning curve cumulative summation (CUSUM) of 3
      dimensional (3D) sonography for diagnosis of congenital uterine anomalies and the
      deviations of the level of trainees' performance at the control-stage CUSUM.
      METHODS: First-year (R1), second-year (R2), and third-year (R3) residents in
      obstetrics and gynecology received a training program to learn how to analyze 3D
      sonographic volumes and to classify congenital uterine anomalies. Each trainee
      worked on 155 3D sonographic volumes from preselected patients. Their results
      were evaluated by learning curve CUSUM and standard CUSUM. The time for each
      volume analysis was calculated for the expert examiner and the trainees. RESULTS:
      Trainees R1, R2, and R3 reached competence at the 85th, 58th, and 40th
      evaluations, respectively, with success rates of 80%, 81%, and 85%, and kept the
      process under control with error levels of less than 4.5% until the end of the
      test. The trainees significantly reduced the average time of the evaluation per
      volume (P < .001). CONCLUSIONS: Learning curve CUSUM provided quantitative
      indicators of the learning evolution of 3D sonography for diagnosis of congenital
      uterine anomalies by obstetrics and gynecology residents. The training received
      by the residents was adequate for diagnosis of congenital uterine anomalies using
      3D sonography.

PMID- 27872416
TI  - Initial Experience With Ultrasound Elastography for Diagnosis of Major Salivary
      Gland Lesions.
AB  - OBJECTIVES: The aim of this study was to evaluate the usefulness of ultrasound
      elastography, including conventional strain elastography, acoustic radiation
      force impulse (ARFI)-induced strain elastography, and point shear wave
      elastography (SWE) for diagnosis of major salivary gland lesions. METHODS: Forty
      major salivary gland lesions underwent conventional sonography, conventional
      strain elastography, ARFI strain elastography, and point SWE before surgery or
      biopsy. The diagnostic performances of the sonographic and elastographic
      techniques were assessed with reference to histopathologic results. RESULTS:
      There were 32 benign (7 Warthin tumors, 17 pleomorphic adenomas, and 8 other
      benign lesions) and 8 malignant (1 squamous carcinoma, 2 metastases, 2
      mucoepidermoid carcinomas, 1 anaplastic carcinoma, and 2 malignant lymphomas)
      major salivary gland lesions on pathologic analysis. No conventional sonographic
      features or conventional strain elastographic scores were found to be associated
      with malignancy (all P > .05). The ARFI strain elastographic scores between
      benign and malignant lesions were statistically different (P = .032) and an ARFI
      strain elastographic score of 4 or greater was highly predictive of malignancy
      (P= .025). An ARFI strain elastographic score of greater than 3 achieved
      specificity of 81.3% (26 of 32) and sensitivity of 62.5% (5 of 8) in
      differentiating benign from malignant lesions. The shear wave velocity on point
      SWE did not show a significant difference in distinguishing between malignant and
      benign lesions (6.07 versus 4.43 m/s; P > .05). However, Warthin tumors had a
      trend to show lower shear wave velocities compared with pleomorphic adenomas
      (2.84 versus 5.27 m/s; P = .024). CONCLUSIONS: Acoustic radiation force impulse
      strain elastography may be potentially useful for diagnosing major salivary gland
      lesions, whereas conventional strain elastography and point SWE are not helpful.

PMID- 27872417
TI  - Virtual Touch Quantification of the Salivary Glands for Diagnosis of Primary
      Sjogren Syndrome.
AB  - OBJECTIVES: To investigate the value of salivary gland stiffness measured by
      Virtual Touch quantification (VTQ; Siemens Medical Solutions, Erlangen, Germany)
      for assessment of primary Sjogren syndrome. METHODS: Fifty-four patients with
      primary Sjogren syndrome, 35 patients without primary Sjogren syndrome (patients
      with dry mouth and dry eye symptoms), and 52 healthy control volunteers were
      included in this study. Patients with primary Sjogren syndrome were classified as
      early or advanced stage by labial gland biopsies. All participants underwent B
      mode sonography, on which the salivary glands (parotid and submandibular) were
      identified and VTQ measurements of shear wave velocity (SWV) were obtained. The
      diagnostic performance of SWV was evaluated by sensitivity and specificity at the
      optimum cutoff point and the area under the receiver operating characteristic
      curve. RESULTS: For submandibular glands, the mean SWV +/- SD values were 2.25 +/
      0.34 m/s in patients with early-stage primary Sjogren, 1.84 +/- 0.20 m/s in
      patients without primary Sjogren syndrome, and 1.82 +/- 0.27 m/s in healthy
      controls (P< .001). With cutoff values of 2.15 and 2.10 m/s to separate patients
      with early-stage primary Sjogren syndrome from those without Sjogren syndrome and
      healthy controls, the sensitivity and specificity were 77.1% and 85.4% and 79.2%
      and 83.9%, respectively. For parotid glands, the SWV values were 2.78 +/- 0.82
      m/s in patients with early-stage primary Sjogren syndrome, 1.93 +/- 0.33 m/s, in
      patients without primary Sjogren syndrome, and 1.85 +/- 0.31 m/s in healthy
      controls (P < .001). With cutoff values of 2.18 and 2.10 m/s to separate patients
      with early-stage primary Sjogren syndrome from those without Sjogren syndrome and
      healthy controls, the sensitivity and specificity were 89.3 % and 75.3% and 91.4%
      and 80.0%. CONCLUSIONS: The VTQ technique might be a useful noninvasive strategy
      for assessment of salivary glands in the early stage of primary Sjogren syndrome.

PMID- 27872418
TI  - Use of Angle-Independent M-Mode Sonography for Assessment of Diaphragm
      Displacement.
AB  - OBJECTIVES: Sonographic assessment of diaphragm displacement has conventionally
      been conducted with M-mode sonography via an anterior subcostal approach. This
      method is subject to measurement errors when diaphragm displacement is not in
      line with the M-mode plane. We aimed to compare measurements obtained by offline
      angle-independent (anatomic) M-mode sonography with conventional M-mode
      sonography. METHODS: Fifty healthy adults were imaged with conventional and angle
      independent M-mode sonography of the bilateral hemidiaphragms at 60% maximal
      inspiratory capacity using an inspiratory spirometer. RESULTS: Left hemidiaphragm
      displacement was successfully imaged by conventional M-mode sonography in only
      70% (n = 35), as lung expansion obscured imaging, whereas 92% (n = 46) were
      assessable by angle-independent M-mode sonography. All right hemidiaphragm
      displacement could be assessed. Conventional M-mode results were higher than
      angle-independent M-mode results on the right (mean +/- SD, 4.9 +/- 1.4 versus
      4.6 +/- 1.2 cm, respectively; P= .003) and left (5.4 +/- 1.3 versus 4.6 +/- 1.0
      cm; P < .001). Displacement values were different for right versus left
      hemidiaphragms on conventional M-mode sonography (mean difference, 0.6 +/- 0.2
      cm; P = .005), with only mild agreement (R2 = 0.35; P < .001). There was no
      laterality seen in the diaphragm displacement on angle-independent M-mode
      sonography (mean difference, 0.1 +/- 0.1 cm; P = .47), with good agreement (R2 =
      0.76; P < .001). CONCLUSIONS: Angle-independent M-mode sonography leads to better
      visualization and assessment of the left hemidiaphragm. It records lower
      displacement than conventional M-mode sonography in the bilateral diaphragms,
      likely because of fewer orientation and translation errors. Future study is
      indicated to assess the clinical utility of angle-independent M-mode sonography
      in a population with diaphragm dysfunction.

PMID- 27872419
TI  - Elastographic Findings of Achilles Tendons in Asymptomatic Professional Male
      Volleyball Players.
AB  - OBJECTIVES: Elastography is a new sonographic technique that evaluates the
      elasticity of different tissues such as the Achilles tendon. In this study, we
      aimed to investigate the elastographic findings of Achilles tendons in
      professional athletes in comparison with healthy volunteers. METHODS: Twenty-one
      professional male volleyball players with no history of Achilles trauma were
      included in this study. Twenty-one healthy male volunteers with similar ages and
      body mass indices were selected as control participants. All participants
      underwent sonographic and elastographic evaluations of the Achilles tendons to
      evaluate Achilles tendon thickness and stiffness. RESULTS: We observed thickening
      in many of the thirds of the Achilles tendons (right proximal, right middle, left
      middle, and left distal thirds) of athletes in comparison with healthy
      volunteers. We did not detect any abnormalities according to the sonographic
      evaluations in both athletes and healthy volunteers. In the elastographic
      evaluations, we observed softening in the middle thirds of the Achilles tendons
      of athletes according to the main types (P < .001) and subtypes (P < .001 for
      right; and P = .002 for left middle third). There was no difference observed in
      the elastographic evaluations of the proximal and distal thirds. CONCLUSIONS: On
      sonography and elastography, we observed thickening and softening in Achilles
      tendons of athletes in comparison with healthy volunteers who had similar ages
      and body mass indices. These changes could be associated with early tendon
      degeneration. Further longitudinal studies may support this consideration.

PMID- 27872420
TI  - Role of Cervical Length Measurement for Preterm Delivery Prediction in Women With
      Threatened Preterm Labor and Cervical Dilatation.
AB  - OBJECTIVES: To compare the accuracy and cutoff points for cervical length for
      predicting preterm delivery in women with threatened preterm labor between those
      with a closed cervix and cervical dilatation. METHODS: We conducted a
      retrospective cohort study of women with singleton pregnancies with threatened
      preterm labor before 34 weeks. The accuracy of cervical length for predicting
      preterm delivery was compared between women with cervical dilatation (0.5-3 cm)
      and those with a closed cervix. The predictive accuracy of cervical length for
      spontaneous preterm delivery was analyzed with several outcome-specific
      thresholds. RESULTS: Overall, 1068 women with threatened preterm labor met the
      inclusion criteria; of them, 276 (25.8%) had cervical dilatation, and 792 (74.2%)
      had a closed cervix. The risk of preterm delivery before 37 weeks was
      significantly higher in the cervical dilatation group than the closed cervix
      group, as well as a shorter assessment-to-delivery interval of within 14 days (P
      = .001 and .004, respectively). On a multivariable analysis, cervical length was
      independently associated with the risk of preterm delivery in both groups. There
      was no significant difference between women with cervical dilatation and those
      with a closed cervix regarding the area under the receiver operating
      characteristic curves of cervical length for prediction of preterm delivery
      before 37 (0.674 versus 0.618; P = .18) and 34 (0.628 versus 0.640; P = .88)
      weeks and an assessment-to-delivery interval of 14 days (0.686 versus 0.660; P=
      .72). The negative predictive value of cervical length ranged from 77.4% to 95.7%
      depending on the different thresholds used. CONCLUSIONS: Cervical length was
      significantly associated with the risk of preterm delivery in women presenting
      with threatened preterm labor and cervical dilatation of less than 3 cm. However,
      the predictive accuracy of cervical length as a single measure was relatively
      limited.

PMID- 27872421
TI  - Risk of Adverse Outcomes in Euploid Pregnancies With Isolated Short Fetal Femur
      and Humerus on Second-Trimester Sonography.
AB  - OBJECTIVES: The purpose of this study was to evaluate pregnancies with isolated
      short fetal femur and humerus on second-trimester sonography. Short fetal long
      bones are known to be associated with aneuploidy and structural anomalies. In
      this study, we wanted to show the risk of adverse pregnancy outcomes in euploid
      and nonanomalous pregnancies. METHODS: Singleton pregnancies with short femur and
      humerus were included. Pregnancies with normal fetal bone lengths and age-matched
      mothers were selected as controls. RESULTS: The study group included 30
      pregnancies with short fetal femur and humerus, and the control group included 60
      normal pregnancies. The overall odds ratio for an adverse pregnancy outcome in
      the study group was 24.9. Preterm delivery occurred significantly more frequently
      (odds ratio, 20.8; P < .001), and one-third of pregnancies were complicated by
      preeclampsia. In the group with short long bones, the odds ratio for a pathologic
      umbilical Doppler flow pattern was 45.2 (P < .001), and birth weight was
      significantly lower (P < .001). Also, 3 (10.3%) stillbirths and 4 (13.3%) cases
      of early neonatal death were recorded in this group. These complications were not
      recorded in the control group. The risk of emergency cesarean delivery was
      significantly higher in the group with short long bones (odds ratio, 11.8; P <
      .001). CONCLUSIONS: The risk of adverse pregnancy outcomes is significant in
      euploid and nonanomalous pregnancies with isolated short long bones. Close follow
      up is needed during pregnancy.

PMID- 27872422
TI  - Spleen Behind the Heart Complicates Lung-to-Head Ratio Measurement in Left-Sided
      Congenital Diaphragmatic Hernia.
AB  - In fetuses with left-sided congenital diaphragmatic hernia, intrathoracic
      herniation of the spleen is a common occurrence. The herniated spleen can reside
      posterior to the left atrium of the heart in the right hemithorax and is
      increasingly differentiated from the lung with the use of newer sonographic
      equipment. Estimation of the neonatal prognosis relies on accurate measurement of
      fetal lung size, particularly with commonly used measurements such as the lung-to
      head ratio. Here we describe how herniation of the spleen behind the heart can
      complicate measurement of the lung-to-head ratio on sonography and lead to
      overestimation, with implications for perinatal prognostication and management.

PMID- 27872423
TI  - Role of Sonography for Evaluation of Gastrointestinal Foreign Bodies.
AB  - Foreign body ingestion is frequently encountered in children. The locations of
      the foreign bodies and the period during which they have been present in the
      thorax and abdomen are important for determining the method and timing of
      treatment. Although plain radiography and computed tomography are primarily used
      for assessment of foreign bodies, sonography without radiation is also useful for
      diagnosis of foreign bodies. This report describes 5 cases of foreign bodies in
      the digestive tract and the usefulness of sonography for real-time evaluation of
      foreign bodies with high spatial resolution. Physicians can use sonography along
      with radiography and computed tomography in cases involving foreign bodies.

PMID- 27872424
TI  - Tricuspid Papillary Muscle Rupture Due to Blunt Chest Trauma.

PMID- 27872425
TI  - Concordant Body Stalk Anomalies in Dichorionic Twins.

PMID- 27872426
TI  - Gastric tube esophageal reconstruction in children with esophageal atresia and
      caustic stricture Study of clinical value based on 25 single-center. Centre
      experience.
AB  - AIM: The aim of this study was estimation of clinical value of gastric tube
      esophagoplasty in children based on one single center experience. METHODS: Forty
      nine patients with diagnosis of EA (n=22) and caustic esophageal injury (n=27)
      had undergone reverse gastric tube esophagoplasty during 25 years at our
      institution. Almost all EA patients received initially gastrostomy and cervical
      esophagostomy. Majority of CS patients had initially repeated dilatation therapy.
      Demographics, preoperative features (initial condition, initial treatment and
      nutritional status) and postoperative features (leakage, stenosis, nutritional
      status and disease-specific symptoms) were retrospectively reviewed and analyzed.
      Mean follow up time was 8.2 years. RESULTS: Of 49 patients, 2 patients died and
      gastric tube failed in one patient. The most common complications were
      anastomotic leak (52%) and anastomotic stricture (47,8%). Disease-specific
      symptoms (dysphagia and reflux symptoms) with important clinical manifestations
      were observed in 10.87% of patients. Preoperatively, all patients were eutrophic.
      One year after operation 96% of patients stayed eutrophic and two EA patients
      were malnourished. CONCLUSION: The most common complications such as anastomotic
      leak and anastomotic stricture may be considered benign. Postoperative nutrition,
      as good indicator of the procedure's adequacy, for the majority of patients is
      satisfactory. Gastric tube esophagoplasty is an appropriate alternative for
      esophageal replacement in children. KEY WORDS: Children, Gastric tube,
      Esophagoplasty.

PMID- 27872428
TI  - Several factors can alter the QTc interval in patients with end-stage renal
      disease.

PMID- 27872427
TI  - Giant lipoma in the thigh A case report.
AB  - : Lipomas are the most common benign mesenchymal tumours; they are composed by
      mature lipocytes and are usually located in the subcutaneous tissue. They may
      occur at any place in which there is adipose tissue, most of them are found in
      the upper part of the body, especially in the trunk and neck, although they may
      also develop in other sites, including the hand. Most lipomas are small, weigh
      only a few grams, and usually the maximum diameter is smaller than 2 cm. Whereas,
      to be referred to as ''giant'', the lipoma must be at least 10 cm in diameter or
      weigh a minimum of 1,000 g. Because of the excessive size, giant lipomas may
      cause functional limitations, such as lymphedema, pain syndromes or nerve
      compression. Because of the peculiarity of this condition, the great size of the
      lesion and the difficulties in its diagnosis and treatment, we reported a case of
      a giant fibrolipoma in the thigh in a 27 years old woman. KEY WORDS: Giant
      lipoma, Lipoma, Lipoma of the leg.

PMID- 27872429
TI  - Author's Reply.

PMID- 27872430
TI  - Polycystic ovary syndrome. Are we overlooking something?

PMID- 27872431
TI  - Author's Reply.

PMID- 27872432
TI  - Postoperative cognitive dysfunction markers in coronary artery surgery.

PMID- 27872433
TI  - Author's Reply.

PMID- 27872434
TI  - SYNTAX score predicts postoperative atrial fibrillation in patients undergoing on
      pump isolated coronary artery bypass grafting surgery.

PMID- 27872435
TI  - Author's Reply.

PMID- 27872436
TI  - Kounis syndrome presenting with acute inferior wall myocardial infarction and
      cardiogenic shock secondary to intravenous ampicillin/sulbactam administration.

PMID- 27872438
TI  - Medication adherence and quality of life in coronary artery bypass grafting
      patients, results of retrospective cohort study.

PMID- 27872441
TI  - Retraction and Beyond.

PMID- 27872437
TI  - Renal artery stenting of chronic kidney disease patient with resistant
      hypertension.

PMID- 27872440
TI  - Successful percutaneous implantation of Symetis ACURATE neo transcatheter aortic
      bioprosthesis in a patient with existing mechanical mitral valve.

PMID- 27872442
TI  - Commentary on the association of blood group antigens with post-implant
      thrombosis of mechanical heart valves.

PMID- 27872443
TI  - Microvolt T-wave alternans testing is abnormal both in left- and right-sided
      pathology.

PMID- 27872444
TI  - Myocardial strain imaging and malignant ventricular arrhythmia risk.

PMID- 27872445
TI  - Searching for mechanical abnormalities in subjects with early repolarization
      pattern: another Holy Grail of cardiac imaging?

PMID- 27872446
TI  - Is increased homocysteine level a false trail or an accomplice to saphenous
      venous graft degeneration?

PMID- 27872448
TI  - Cigarette smoking: number one enemy for Graves ophthalmopathy.

PMID- 27872449
TI  - Gone with the age(DL): high-density lipoprotein in senescence.

PMID- 27872447
TI  - Evolving approaches to heart regeneration by therapeutic stimulation of resident
      cardiomyocyte cell cycle.
AB  - Heart has long been considered a terminally differentiated organ. Recent studies,
      however, have suggested that there is a modest degree of cardiomyocyte (CM)
      turnover in adult mammalian heart, albeit not sufficient for replacement of lost
      CMs following cardiac injuries. Cardiac regeneration studies in various model
      organisms including zebrafish, newt, and more recently in neonatal mouse, have
      demonstrated that CM dedifferentiation and concomitant proliferation play
      important roles in replacement of lost CMs and restoration of cardiac
      contractility. Further studies with neonatal cardiac regeneration mouse model
      suggested that major source of new CMs is existing CMs, with the possibility of
      involvement of cardiac stem cells. Numerous studies have now been conducted on
      induction of cardiac regeneration and have identified various cardiogenic
      factors, cardiogenic micro ribonucleic acid and cardiogenic small molecules. This
      report is a review of studies regarding generation of CM and prospects for
      application.

PMID- 27872450
TI  - Prepregnancy care: improvements for some women but not for all!

PMID- 27872451
TI  - Update on the mechanisms of action of anti-TNF-alpha antibodies and their
      clinical implications in inflammatory bowel disease.
AB  - The mechanisms of action of antitumor necrosis factor alpha (anti-TNF-alpha)
      antibodies in the therapy of inflammatory bowel disease (IBD) are not completely
      understood. Binding of antibodies to transmembrane TNF-alpha seems to be crucial
      for the induction of several cellular responses, including complement-dependent
      cytotoxicity, antibody-dependent cellular cytotoxicity, and reverse signaling.
      However, these processes alone do not fully explain the diversity of responses to
      anti-TNF-alpha therapy seen in different patients. Thus, the present review aimed
      to discuss the current role of anti-TNF-alpha antibodies in treatment algorithms
      for IBD as well as the current knowledge on the mechanisms of action of these
      antibodies, particularly the less well known aspects of anti-TNF-alpha blockade.
      We also discussed a complex role of particular macrophage subpopulations, T
      regulatory cells, and intestinal endothelial cells, as well as presented new data
      on the clinical relevance of anti-inflammatory responses attributed to the Fc
      region of anti-TNF-alpha antibodies.

PMID- 27872452
TI  - How to treat ANCA-associated vasculitis: practical messages from 2016 EULAR/ERA
      EDTA recommendations.
AB  - The European League against Rheumatism (EULAR) with the European Renal
      Association - European Dialysis and Transplant Association recently published an
      update of 2009 EULAR recommendations with a focus on the management of
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). In this
      article, we discuss the following key messages for clinical practice derived from
      these recommendations: 1) biopsy should be performed if possible to confirm new
      diagnosis or relapse; 2) glucocorticoid therapy is an extremely important adjunct
      to the management of AAV, but it is also responsible for the majority of adverse
      effects; the dose should be tapered to 7.5 to 10 mg/d at 3 to 5 months; 3)
      cyclophosphamide or rituximab are the mainstay of remission induction; 4)
      patients with major relapse should be treated like those with new disease, but
      rituximab is the preferred option in those patients who relapse after prior
      cyclophosphamide; 5) minor relapse should not be treated with glucocorticoid
      alone, and a change in immunosuppressive regimen should be considered; 6)
      rituximab can be used not only for remission induction but also for maintenance;
      7) maintenance therapy should continue for at least 2 years, after which gradual
      taper could be considered; 8) while ANCA are extremely useful for diagnosis and
      rising ANCA levels seem to be associated with relapse, serial monitoring should
      not guide treatment decisions; 9) monitoring of AAV patients should be holistic
      with a structured assessment tool and monitoring for effects related to the
      vasculitis as well as treatment; 10) management should be either at or in
      conjunction with an expert center; and 11) patients should be involved in
      decision making and have access to educational resources.

PMID- 27872453
TI  - Huge interventricular septal aneurysm diagnosed in vivo in an adult.

PMID- 27872454
TI  - Do not consider amiodarone, give it! Comment on antiarrhythmic drugs for shock
      refractory ventricular fibrillation or pulseless ventricular tachycardia.

PMID- 27872455
TI  - Resuscitation in sepsis in 2016. What's new? Dr. Waleed Alhazzani in an interview
      with Dr. Roman Jaeschke: part 1.

PMID- 27872456
TI  - Stress ulcer prophylaxis in critical care: a 2016 perspective Dr. Waleed
      Alhazzani in an interview with Dr. Roman Jaeschke: part 2.

PMID- 27872457
TI  - BRIDGE trial. Dr. James Douketis in an interview with Dr. Roman Jaeschke: part 1.

PMID- 27872458
TI  - Periprocedural risk of bleeding and thrombosis: to bridge or not to bridge. Dr.
      James Douketis in an interview with Dr. Roman Jaeschke: part 2.

PMID- 27872460
TI  - SPRINT trial and blood pressure treatment. Dr. Gordon Guyatt in an interview with
      Dr. Roman Jaeschke.

PMID- 27872459
TI  - Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes
      mellitus. Dr. Hertzel Gerstein in an interview with Dr. Roman Jaeschke.

PMID- 27872461
TI  - Contraception in questions and answers.

PMID- 27872462
TI  - Heart failure in questions and answers.

PMID- 27872463
TI  - Reflections on the current situation and the future of internal medicine in
      Poland.

PMID- 27872464
TI  - Forum for internal medicine: opinions and controversies.

PMID- 27872465
TI  - Internal medicine through a scientist's eye.

PMID- 27872466
TI  - Internal medicine and biomedicine in Poland: views from the inside and outside.

PMID- 27872467
TI  - Abandonment of internal medicine as a specialty: the point of no return?

PMID- 27872468
TI  - Internal medicine as the queen of medical sciences: an underestimated
      specialization in Poland.

PMID- 27872470
TI  - Hereditary Amyloidosis with Recurrent Lung Infiltrates.
AB  - BACKGROUND Amyloidosis is a protein conformational disorder characterized by
      extracellular deposition of amyloid fibrils in extracellular tissue. Lung
      involvement is most commonly caused by secondary AL amyloidosis. The familial
      autosomal-dominant senile transthyretin (ATTR) disease manifests mainly as
      polyneuropathy and restrictive cardiomyopathy denoting the name familial
      amyloidotic polyneuropathy (FAP). Rarely, this form manifests with clinical and
      radiologically relevant respiratory tract symptoms and lung involvement. CASE
      REPORT A 51-year-old male former smoker presented with progressive lower
      extremity weakness of several months' duration. He was ultimately diagnosed with
      chronic demyelinating polyneuropathy and treated with intravenous immunoglobulin
      therapy. Subsequently, he was admitted with heart failure symptoms and pulmonary
      infiltrates and his echocardiogram showed a 'myocardial speckled pattern',
      prompting an endomyocardial biopsy, which showed transthyretin amyloid
      deposition. He was started on diflunisal. Additionally, serial radiographic
      imaging of his chest over 3 different admissions for cough, dyspnea, hypoxemia,
      and lethargy demonstrated recurrent pulmonary infiltrates. A fiberoptic
      bronchoscopy with trans-bronchial biopsies revealed amyloid deposition in the
      lung tissue. CONCLUSIONS The clinical presentation of recurrent or persistent
      pulmonary symptoms and fleeting infiltrates on imaging in a patient with familial
      amyloidotic polyneuropathy is not common; when present, it should raise the
      suspicion of respiratory tract involvement.

PMID- 27872469
TI  - Preoperative Serum MicroRNA-155 Expression Independently Predicts Postoperative
      Cognitive Dysfunction After Laparoscopic Surgery for Colon Cancer.
AB  - BACKGROUND The aim of this study was to examine the association between serum
      expression of miRNA-155 and postoperative cognitive dysfunction (POCD) after
      laparoscopic surgery for colon cancer. MATERIAL AND METHODS We enrolled 110
      patients scheduled to undergo colon tumor resection via laparotomy in Ningbo No.
      2 Hospital from July 2013 to November 2015. The blood samples were collected from
      the participants 1 day before surgery. Multiple logistic regression analysis was
      used for the analysis of independent predictive biomarkers for POCD. RESULTS On
      the 7th postoperative day, 29 of the 110 participants developed POCD, yielding a
      POCD incidence of 26.4%. Age, MMSE score, duration of surgery and anesthesia,
      serum levels of CRP, TNF-alpha, urea, creatinine, and miRNA-155 were highly
      associated with the occurrence of POCD. Serum expression of miRNA-155 was shown
      by multiple logistic regression analysis to be an independent predictive
      indicator for POCD after surgery (OR: 2.732; 95%CI 1.415-5.233; P=0.002).
      CONCLUSIONS The serum expression of miRNA-155 is an independent predictive factor
      for POCD after laparoscopic surgery for colon cancer.

PMID- 27872471
TI  - Recent Progress in Xenotransplantation, with Emphasis on Virological Safety.
AB  - Xenotransplantation is a new technology that may help to overcome the shortage of
      human tissues and organs available for the treatment of tissue and organ failure.
      Remarkable progress has recently been made in this field. First, understanding of
      the mechanisms of immunological rejection, mainly of the hyperacute rejection,
      allowed generating numerous genetically modified pigs to overcome rejection.
      Second, based on these genetically modified animals and new immunosuppression
      regimens, long-term survival of non-human primate recipients of heart, kidney,
      and islet cell cells has been reported. And third, potential zoonotic
      microorganisms have been identified in pigs and sensitive methods to detect them
      have been generated. In 2 clinical trials treating diabetic patients with porcine
      islet cells, no porcine microorganisms were transmitted to human recipients.
      Furthermore, strategies to eliminate potentially zoonotic microorganisms from
      donor pigs in order to prevent transmission to the recipients have been
      developed, including designated pathogen-free (DPF) breeding. In addition,
      strategies to prevent transmission of porcine endogenous retroviruses (PERVs)
      have been developed, including a knockout of all proviruses in the pig genome by
      gene editing. PERVs are integrated in the genome of all pigs and therefore they
      cannot be eliminated by DPF breeding. Since they are able to infect human cells,
      they represent a special risk in xenotransplantation. Despite the achievements,
      some problems remain: numerous genetically multi-modified pigs have been
      generated without fully evaluating their advantage, and microbiological screening
      of pigs to be used for transplantations and elimination of pathogenic
      microorganisms from the donor pigs are still not satisfactory.

PMID- 27872473
TI  - Increasing entropy for colloidal stabilization.
AB  - Stability is of paramount importance in colloidal applications. Attraction
      between colloidal particles is believed to lead to particle aggregation and phase
      separation; hence, stability improvement can be achieved through either
      increasing repulsion or reducing attraction by modifying the fluid medium or by
      using additives. Two traditional mechanisms for colloidal stability are
      electrostatic stabilization and steric stabilization. However, stability
      improvement by mixing attractive and unstable particles has rarely been
      considered. Here, we emphasize the function of mixing entropy in colloidal
      stabilization. Dispersion stability improvement is demonstrated by mixing
      suspensions of attractive nanosized titania spheres and platelets. A three
      dimensional phase diagram is proposed to illustrate the collaborative effects of
      particle mixing and particle attraction on colloidal stability. This discovery
      provides a novel method for enhancing colloidal stability and opens a novel
      opportunity for engineering applications.

PMID- 27872472
TI  - Hierarchical effects of pro-inflammatory cytokines on the post-influenza
      susceptibility to pneumococcal coinfection.
AB  - In the course of influenza A virus (IAV) infections, a secondary bacterial
      infection frequently leads to serious respiratory conditions provoking high
      hospitalization and death tolls. Although abundant pro-inflammatory responses
      have been reported as key contributing factors for these severe dual infections,
      the relative contributions of cytokines remain largely unclear. In the current
      study, mathematical modelling based on murine experimental data dissects IFN
      gamma as a cytokine candidate responsible for impaired bacterial clearance,
      thereby promoting bacterial growth and systemic dissemination during acute IAV
      infection. We also found a time-dependent detrimental role of IL-6 in curtailing
      bacterial outgrowth which was not as distinct as for IFN-gamma. Our numerical
      simulations suggested a detrimental effect of IFN-gamma alone and in synergism
      with IL-6 but no conclusive pathogenic effect of IL-6 and TNF-alpha alone. This
      work provides a rationale to understand the potential impact of how to manipulate
      temporal immune components, facilitating the formulation of hypotheses about
      potential therapeutic strategies to treat coinfections.

PMID- 27872474
TI  - Multi-level glyco-engineering techniques to generate IgG with defined Fc-glycans.
AB  - Immunoglobulin G (IgG) mediates its immune functions through complement and
      cellular IgG-Fc receptors (FcgammaR). IgG contains an evolutionary conserved N
      linked glycan at position Asn297 in the Fc-domain. This glycan consists of
      variable levels of fucose, galactose, sialic acid, and bisecting N
      acetylglucosamine (bisection). Of these variations, the lack of fucose strongly
      enhances binding to the human FcgammaRIII, a finding which is currently used to
      improve the efficacy of therapeutic monoclonal antibodies. The influence of the
      other glycan traits is largely unknown, mostly due to lack of glyco-engineering
      tools. We describe general methods to produce recombinant proteins of any desired
      glycoform in eukaryotic cells. Decoy substrates were used to decrease the level
      of fucosylation or galactosylation, glycosyltransferases were transiently
      overexpressed to enhance bisection, galactosylation and sialylation and in vitro
      sialylation was applied for enhanced sialylation. Combination of these techniques
      enable to systematically explore the biological effect of these glycosylation
      traits for IgG and other glycoproteins.

PMID- 27872475
TI  - Systemic lupus erythematosus: Extent and patterns of off-label use of rituximab
      for SLE.

PMID- 27872478
TI  - Circulating tumour cells as biomarkers of prostate, bladder, and kidney cancer.
AB  - Circulating tumour cells (CTCs) have been studied as biomarkers of a number of
      solid malignancies. Potential clinical applications for CTC analysis include
      early cancer detection, disease staging, monitoring for recurrence,
      prognostication, and to aid in the selection of therapy. In the field of urologic
      oncology, CTCs have been most widely studied as prognostic biomarkers of
      castration-resistant prostate cancer. Additionally, emerging data support a role
      for CTCs to help identify which patients are most likely to respond to novel
      androgen-pathway targeted therapies, such as abiraterone and enzalutamide. CTCs
      have also been studied as predictive biomarkers of bladder cancer, in particular
      as a means to identify patients whose disease has been clinically understaged.
      Less is known regarding CTCs in kidney cancer; this has been attributed to the
      fact that a minority of renal tumours express EpCAM, the epithelial cell surface
      protein commonly used by CTC assays for positive cell selection. However,
      alternative approaches using markers specific for kidney cancer are being
      explored.

PMID- 27872479
TI  - Surgery: The surgeon-scientist - a dying breed?

PMID- 27872480
TI  - Association of pre-pregnancy body mass index, gestational weight gain with
      cesarean section in term deliveries of China.
AB  - China has one of the highest rates of cesarean sections in the world. However,
      limited epidemiological studies have evaluated the risk factors for cesarean
      section among Chinese women. Thus, the aim of this cohort study was to
      investigate the associations between pre-pregnancy BMI, gestational weight gain
      (GWG) and the risk of cesarean section in China. A total of 57,891 women with
      singleton, live-born, term pregnancies were included in this analysis. We found
      that women who were overweight or obese before pregnancy had an elevated risk of
      cesarean section. Women with a total GWG above the Institute of Medicine (IOM)
      recommendations had an adjusted OR for cesarean section of 1.45 (95% CI, 1.40
      1.51) compared with women who had GWG within the IOM recommendations. Women with
      excessive BMI gain during pregnancy also had an increased risk of cesarean
      section. When stratified by maternal pre-pregnancy BMI, there was a significant
      association between excessive GWG and increased odds of cesarean section across
      all pre-pregnancy BMI categories. These results suggest that weight control
      efforts before and during pregnancy may help to reduce the rate of cesarean
      sections.

PMID- 27872477
TI  - The role of GATA2 in lethal prostate cancer aggressiveness.
AB  - Advanced prostate cancer is a classic example of the intractability and
      consequent lethality that characterizes metastatic carcinomas. Novel treatments
      have improved the survival of men with prostate cancer; however, advanced
      prostate cancer invariably becomes resistant to these therapies and ultimately
      progresses to a lethal metastatic stage. Consequently, detailed knowledge of the
      molecular mechanisms that control prostate cancer cell survival and progression
      towards this lethal stage of disease will benefit the development of new
      therapeutics. The transcription factor endothelial transcription factor GATA-2
      (GATA2) has been reported to have a key role in driving prostate cancer
      aggressiveness. In addition to being a pioneer transcription factor that
      increases androgen receptor (AR) binding and activity, GATA2 regulates a core
      subset of clinically relevant genes in an AR-independent manner. Functionally,
      GATA2 overexpression in prostate cancer increases cellular motility and
      invasiveness, proliferation, tumorigenicity, and resistance to standard
      therapies. Thus, GATA2 has a multifaceted function in prostate cancer
      aggressiveness and is a highly attractive target in the development of novel
      treatments against lethal prostate cancer.

PMID- 27872482
TI  - Development of a rapid screen for the endodermal differentiation potential of
      human pluripotent stem cell lines.
AB  - A challenge facing the human pluripotent stem cell (hPSC) field is the
      variability observed in differentiation potential of hPSCs. Variability can lead
      to time consuming and costly optimisation to yield the cell type of interest.
      This is especially relevant for the differentiation of hPSCs towards the
      endodermal lineages. Endodermal cells have the potential to yield promising new
      knowledge and therapies for diseases affecting multiple organ systems, including
      lung, thymus, intestine, pancreas and liver, as well as applications in
      regenerative medicine and toxicology. Providing a means to rapidly, cheaply and
      efficiently assess the differentiation potential of multiple hPSCs is of great
      interest. To this end, we have developed a rapid small molecule based screen to
      assess the endodermal potential (EP) of hPSCs, based solely on definitive
      endoderm (DE) morphology. This drastically reduces the cost and time to identify
      lines suitable for use in deriving endodermal lineages. We demonstrate the
      efficacy of this screen using 10 different hPSCs, including 4 human embryonic
      stem cell lines (hESCs) and 6 human induced pluripotent stem cell lines (hiPSCs).
      The screen clearly revealed lines amenable to endodermal differentiation, and
      only lines that passed our morphological assessment were capable of further
      differentiation to hepatocyte like cells (HLCs).

PMID- 27872476
TI  - New insights into the immunopathogenesis of systemic lupus erythematosus.
AB  - The aetiology of systemic lupus erythematosus (SLE) is multifactorial, and
      includes contributions from the environment, stochastic factors, and genetic
      susceptibility. Great gains have been made in understanding SLE through the use
      of genetic variant identification, mouse models, gene expression studies, and
      epigenetic analyses. Collectively, these studies support the concept that
      defective clearance of immune complexes and biological waste (such as apoptotic
      cells), neutrophil extracellular traps, nucleic acid sensing, lymphocyte
      signalling, and interferon production pathways are all central to loss of
      tolerance and tissue damage. Increased understanding of the pathogenesis of SLE
      is driving a renewed interest in targeted therapy, and researchers are now on the
      verge of developing targeted immunotherapy directed at treating either specific
      organ system involvement or specific subsets of patients with SLE. Accordingly,
      this Review places these insights within the context of our current understanding
      of the pathogenesis of SLE and highlights pathways that are ripe for therapeutic
      targeting.

PMID- 27872481
TI  - Imaging Cellular Dynamics with Spectral Relaxation Imaging Microscopy: Distinct
      Spectral Dynamics in Golgi Membranes of Living Cells.
AB  - Spectral relaxation from fluorescent probes is a useful technique for determining
      the dynamics of condensed phases. To this end, we have developed a method based
      on wide-field spectral fluorescence lifetime imaging microscopy to extract
      spectral relaxation correlation times of fluorescent probes in living cells. We
      show that measurement of the phase and modulation of fluorescence from two
      wavelengths permit the identification and determination of excited state
      lifetimes and spectral relaxation correlation times at a single modulation
      frequency. For NBD fluorescence in glycerol/water mixtures, the spectral
      relaxation correlation time determined by our approach exhibited good agreement
      with published dielectric relaxation measurements. We applied this method to
      determine the spectral relaxation dynamics in membranes of living cells.
      Measurements of the Golgi-specific C6-NBD-ceramide probe in living HeLa cells
      revealed sub-nanosecond spectral dynamics in the intracellular Golgi membrane and
      slower nanosecond spectral dynamics in the extracellular plasma membrane. We
      interpret the distinct spectral dynamics as a result of structural plasticity of
      the Golgi membrane relative to more rigid plasma membranes. To the best of our
      knowledge, these results constitute one of the first measurements of Golgi
      rotational dynamics.

PMID- 27872483
TI  - Targeted delivery system for cancer cells consist of multiple ligands conjugated
      genetically modified CCMV capsid on doxorubicin GNPs complex.
AB  - Targeted nano-delivery vehicles were developed from genetically modified Cowpea
      chlorotic mottle virus (CCMV) capsid by ligands bioconjugation for efficient drug
      delivery in cancer cells. RNA binding (N 1-25aa) and beta-hexamer forming (N 27
      41aa) domain of capsid was selectively deleted by genetic engineering to achieve
      the efficient in vitro assembly without natural cargo. Two variants of capsids
      were generated by truncating 41 and 26 amino acid from N terminus (NDelta41 and
      NDelta26) designated as F1 and F2 respectively. These capsid were optimally self
      assembled in 1:2 molar ratio (F1:F2) to form a monodisperse nano-scaffold of size
      28 nm along with chemically conjugated modalities for visualization (fluorescent
      dye), targeting (folic acid, FA) and anticancer drug (doxorubicin). The cavity of
      the nano-scaffold was packed with doxorubicin conjugated gold nanoparticles (10
      nm) to enhance the stability, drug loading and sustained release of drug. The
      chimeric system was stable at pH range of 4-8. This chimeric nano-scaffold system
      showed highly specific receptor mediated internalization (targeting) and ~300%
      more cytotoxicity (with respect to FA- delivery system) to folate receptor
      positive Michigan Cancer Foundation-7 (MCF7) cell lines. The present system may
      offer a programmable nano-scaffold based platform for developing
      chemotherapeutics for cancer.

PMID- 27872484
TI  - Co-occurrence of Local Anisotropic Gradient Orientations (CoLlAGe): A new
      radiomics descriptor.
AB  - In this paper, we introduce a new radiomic descriptor, Co-occurrence of Local
      Anisotropic Gradient Orientations (CoLlAGe) for capturing subtle differences
      between benign and pathologic phenotypes which may be visually indistinguishable
      on routine anatomic imaging. CoLlAGe seeks to capture and exploit local
      anisotropic differences in voxel-level gradient orientations to distinguish
      similar appearing phenotypes. CoLlAGe involves assigning every image voxel an
      entropy value associated with the co-occurrence matrix of gradient orientations
      computed around every voxel. The hypothesis behind CoLlAGe is that benign and
      pathologic phenotypes even though they may appear similar on anatomic imaging,
      will differ in their local entropy patterns, in turn reflecting subtle local
      differences in tissue microarchitecture. We demonstrate CoLlAGe's utility in
      three clinically challenging classification problems: distinguishing (1)
      radiation necrosis, a benign yet confounding effect of radiation treatment, from
      recurrent tumors on T1-w MRI in 42 brain tumor patients, (2) different molecular
      sub-types of breast cancer on DCE-MRI in 65 studies and (3) non-small cell lung
      cancer (adenocarcinomas) from benign fungal infection (granulomas) on 120 non
      contrast CT studies. For each of these classification problems, CoLlAGE in
      conjunction with a random forest classifier outperformed state of the art
      radiomic descriptors (Haralick, Gabor, Histogram of Gradient Orientations).

PMID- 27872485
TI  - The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and
      oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and
      TRPV1 channels.
AB  - Dexmedetomidine (DEX) may act as an antioxidant through regulation of TRPM2 and
      TRPV1 channel activations in the neurons by reducing cerebral ischemia-induced
      oxidative stress and apoptosis. The neuroprotective roles of DEX were tested on
      cerebral ischemia (ISC) in the cultures of rat primary hippocampal and DRG
      neurons. Fifty-six rats were divided into five groups. A placebo was given to
      control, sham control, and ISC groups, respectively. In the third group, ISC was
      induced. The DEX and ISC+DEX groups received intraperitoneal DEX (40 MUg/kg) 3,
      24, and 48 hours after ISC induction. DEX effectively reversed capsaicin and
      cumene hydroperoxide/ADP-ribose-induced TRPV1 and TRPM2 densities and cytosolic
      calcium ion accumulation in the neurons, respectively. In addition, DEX
      completely reduced ISC-induced oxidative toxicity and apoptosis through
      intracellular reactive oxygen species production and depolarization of
      mitochondrial membrane. The DEX and ISC+DEX treatments also decreased the
      expression levels of caspase 3, caspase 9, and poly (ADP-ribose) polymerase in
      the hippocampus and DRG. In conclusion, the current results are the first to
      demonstrate the molecular level effects of DEX on TRPM2 and TRPV1 activation.
      Therefore, DEX can have remarkable neuroprotective impairment effects in the
      hippocampus and DRG of ISC-induced rats.

PMID- 27872487
TI  - Competition Between Resonant Plasmonic Coupling and Electrostatic Interaction in
      Reduced Graphene Oxide Quantum Dots.
AB  - The light emission from reduced graphene oxide quantum dots (rGO-QDs) exhibit a
      significant enhancement in photoluminescence (PL) due to localized surface
      plasmon (LSP) interactions. Silver and gold nanoparticles (NPs) coupled to rGO
      nanoparticles exhibit the effect of resonant LSP coupling on the emission
      processes. Enhancement of the radiative recombination rate in the presence of Ag
      NPs induced LSP tuned to the emission energy results in a four-fold increase in
      PL intensity. The localized field due to the resonantly coupled LSP modes induces
      n-pi* transitions that are not observed in the absence of the resonant
      interaction of the plasmons with the excitons. An increase in the density of the
      Ag-NPs result in a detuning of the LSP energy from the emission energy of the
      nanoparticles. The detuning is due to the cumulative effect of the red-shift in
      the LSP energy and the electrostatic field induced blue shift in the PL energy of
      the rGO-QDs. The detuning quenches the PL emission from rGO-QDs at higher
      concentration of Ag NPs due to non-dissipative effects unlike plasmon induced
      Joule heating that occurs under resonance conditions. An increase in Au
      nanoparticles concentration results in an enhancement of PL emission due to
      electrostatic image charge effect.

PMID- 27872486
TI  - Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through
      the RCAN1 pathway.
AB  - Preclinical changes that precede the onset of symptoms and eventual diagnosis of
      Alzheimer's disease (AD) are a target for potential preventive interventions. A
      large body of evidence suggests that inflammation is closely associated with AD
      pathogenesis and may be a promising target pathway for such interventions.
      However, little is known about the association between systemic inflammation and
      preclinical AD pathophysiology. We first examined whether the acute-phase
      protein, alpha-2 macroglobulin (A2M), a major component of the innate immune
      system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury
      in preclinical AD and risk of incident AD in the predictors of cognitive decline
      among normal individuals (BIOCARD) cohort. We find that A2M concentration in
      blood is significantly associated with CSF concentrations of the neuronal injury
      markers, tau and phosphorylated tau, and that higher baseline serum A2M
      concentration is associated with an almost threefold greater risk of progression
      to clinical symptoms of AD in men. These findings were replicated in the
      Alzheimer's Disease Neuroimaging (ADNI) study. Then, utilizing a systems level
      approach combining large multi-tissue gene expression datasets with mass
      spectrometry-based proteomic analyses of brain tissue, we identified an A2M gene
      network that includes regulator of calcineurin (RCAN1), an inhibitor of
      calcineurin, a well-characterized tau phosphatase. A2M gene and protein
      expression in the brain were significantly associated with gene and protein
      expression levels of calcineurin. Collectively these novel findings suggest that
      A2M is associated with preclinical AD, reflects early neuronal injury in the
      disease course and may be responsive to tau phosphorylation in the brain through
      the RCAN1-calcineurin pathway.

PMID- 27872488
TI  - PLD1 regulates adipogenic differentiation through mTOR - IRS-1 phosphorylation at
      serine 636/639.
AB  - Phospholipase D1 (PLD1) plays a known role in several differentiation processes,
      but its role in adipogenic differentiation remains unknown. In the present study,
      we identified PLD1 as a negative regulator of adipogenic differentiation. We
      showed that PLD activity was downregulated by both 3-Isobutyl-1-methylxanthine
      (IBMX) and insulin upon induction of differentiation in 3T3-L1 adipogenic cells.
      In line with this observation, PLD activity decreased in both high fat diet (HFD)
      fed mice and ob/ob mice. We also found that differentiation of 3T3-L1
      preadipocytes was enhanced by the depletion of PLD1 levels or inhibition of PLD1
      activity by VU0155069, a PLD1-specific inhibitor. Conversely, treatment with
      phosphatidic acid (PA), a PLD product, and overexpression of PLD1 both caused a
      decrease in adipogenic differentiation. Moreover, the elevated differentiation in
      PLD1-knockdown 3T3-L1 cells was reduced by either PA treatment or PLD1
      expression, confirming negative roles of PLD1 and PA in adipogenic
      differentiation. Further investigation revealed that PA displaces DEP domain
      containing mTOR-interacting protein (DEPTOR) from mTORC1, which subsequently
      phosphorylates insulin receptor substrate-1 (IRS-1) at serine 636/639 in 3T3-L1
      cells. Taken together, our findings provide convincing evidence for a direct role
      of PLD1 in adipogenic differentiation by regulating IRS-1 phosphorylation at
      serine 636/639 through DEPTOR displacement and mTOR activation.

PMID- 27872491
TI  - Solid-liquid density and spin crossovers in (Mg, Fe)O system at deep mantle
      conditions.
AB  - The low/ultralow-velocity zones in the Earth's mantle can be explained by the
      presence of partial melting, critically depending on density contrast between the
      melt and surrounding solid mantle. Here, first-principles molecular dynamics
      simulations of (Mg, Fe) O ferropericlase in the solid and liquid states show that
      their densities increasingly approach each other as pressure increases. The
      isochemical density difference between them diminishes from 0.78 (+/-0.7) g/cm3
      at zero pressure (3000 K) to 0.16 (+/-0.04) g/cm3 at 135 GPa (4000 K) for pure
      and alloyed compositions containing up to 25% iron. The simulations also predict
      a high-spin to low-spin transition of iron in the liquid ferropericlase gradually
      occurring over a pressure interval centered at 55 GPa (4000 K) accompanied by a
      density increase of 0.14 (+/-0.02) g/cm3. Temperature tends to widen the
      transition to higher pressure. The estimated iron partition coefficient between
      the solid and liquid ferropericlase varies from 0.3 to 0.6 over the pressure
      range of 23 to 135 GPa. Based on these results, an excess of as low as 5% iron
      dissolved in the liquid could cause the solid-liquid density crossover at
      conditions of the lowermost mantle.

PMID- 27872489
TI  - Experience-Driven Differences in Childhood Cortisol Predict Affect-Relevant Brain
      Function and Coping in Adolescent Monozygotic Twins.
AB  - Stress and emotion involve diverse developmental and individual differences.
      Partially attributed to the development of the prefrontal cortex (PFC), the
      amygdala, and hypothalamic-pituitary-adrenal axis, the precise genetic and
      experiential contributions remain unknown. In previous work, childhood basal
      cortisol function predicted adolescent resting-state functional connectivity (rs
      FC) and psychopathology. To parse experience-driven (non-genetic) contributions,
      we investigated these relations with a monozygotic (MZ) twin design.
      Specifically, we examined whether intrapair differences in childhood afternoon
      cortisol levels predicted cotwin differences in adolescent brain function and
      coping. As expected, intrapair differences in childhood cortisol forecast
      amygdala-perigenual PFC rs-FC (R2 = 0.84, FWE-corrected p = 0.01), and amygdala
      recovery following unpleasant images (R2 = 0.40, FWE-corrected p < 0.05), such
      that the cotwin with higher childhood cortisol evinced relatively lower rs-FC and
      poorer amygdala recovery in adolescence. Cotwin differences in amygdala recovery
      also predicted coping styles. These data highlight experience-dependent change in
      childhood and adolescence.

PMID- 27872493
TI  - Imaging of surface spin textures on bulk crystals by scanning electron
      microscopy.
AB  - Direct observation of magnetic microstructures is vital for advancing spintronics
      and other technologies. Here we report a method for imaging surface domain
      structures on bulk samples by scanning electron microscopy (SEM). Complex
      magnetic domains, referred to as the maze state in CoPt/FePt alloys, were
      observed at a spatial resolution of less than 100 nm by using an in-lens annular
      detector. The method allows for imaging almost all the domain walls in the mazy
      structure, whereas the visualisation of the domain walls with the classical SEM
      method was limited. Our method provides a simple way to analyse surface domain
      structures in the bulk state that can be used in combination with SEM functions
      such as orientation or composition analysis. Thus, the method extends
      applications of SEM-based magnetic imaging, and is promising for resolving
      various problems at the forefront of fields including physics, magnetics,
      materials science, engineering, and chemistry.

PMID- 27872492
TI  - In situ synthesis, enhanced luminescence and application in dye sensitized solar
      cells of Y2O3/Y2O2S:Eu3+ nanocomposites by reduction of Y2O3:Eu3.
AB  - Y2O3/Y2O2S:Eu3+ nanocomposites were successfully prepared by reducing Y2O3:Eu3+
      nanocrystals. The obtained Y2O3/Y2O2S:Eu3+ nanocomposites not only can emit
      enhanced red luminescence excited at 338 nm, but also can be used to improve the
      efficiency of the dye sensitized solar cells, resulting an efficiency of 8.38%,
      which is a noticeable enhancement of 12% compared to the cell without
      Y2O3/Y2O2S:Eu3+ nanocomposites. The results of the incident photon to current,
      dynamic light scattering, and diffuse reflectance spectra indicated that the
      enhancement of the cell efficiency was mainly related to the light scattering
      effect of Y2O3/Y2O2S:Eu3+ nanocomposites. As a phosphor powder, the emission at
      ~615 nm of Y2O3/Y2O2S:Eu3+ was split into two sub-bands. Compared with Y2O3:Eu3+,
      the 5D0 -> 7F0 and 5D0 -> 7F1 emissions of Y2O3/Y2O2S:Eu3+ showed a little red
      shift.

PMID- 27872490
TI  - Use of Zebrafish Larvae as a Multi-Endpoint Platform to Characterize the Toxicity
      Profile of Silica Nanoparticles.
AB  - Nanomaterials are being extensively produced and applied in society. Human and
      environmental exposures are, therefore, inevitable and so increased attention is
      being given to nanotoxicity. While silica nanoparticles (NP) are one of the top
      five nanomaterials found in consumer and biomedical products, their toxicity
      profile is poorly characterized. In this study, we investigated the toxicity of
      silica nanoparticles with diameters 20, 50 and 80 nm using an in vivo zebrafish
      platform that analyzes multiple endpoints related to developmental, cardio-,
      hepato-, and neurotoxicity. Results show that except for an acceleration in
      hatching time and alterations in the behavior of zebrafish embryos/larvae, silica
      NPs did not elicit any developmental defects, nor any cardio- and hepatotoxicity.
      The behavioral alterations were consistent for both embryonic photomotor and
      larval locomotor response and were dependent on the concentration and the size of
      silica NPs. As embryos and larvae exhibited a normal touch response and early
      hatching did not affect larval locomotor response, the behavior changes observed
      are most likely the consequence of modified neuroactivity. Overall, our results
      suggest that silica NPs do not cause any developmental, cardio- or
      hepatotoxicity, but they pose a potential risk for the neurobehavioral system.

PMID- 27872494
TI  - As-grown graphene/copper nanoparticles hybrid nanostructures for enhanced
      intensity and stability of surface plasmon resonance.
AB  - The transfer-free fabrication of the high quality graphene on the metallic
      nanostructures, which is highly desirable for device applications, remains a
      challenge. Here, we develop the transfer-free method by direct chemical vapor
      deposition of the graphene layers on copper (Cu) nanoparticles (NPs) to realize
      the hybrid nanostructures. The graphene as-grown on the Cu NPs permits full
      electric contact and strong interactions, which results in a strong localization
      of the field at the graphene/copper interface. An enhanced intensity of the
      localized surface plasmon resonances (LSPRs) supported by the hybrid
      nanostructures can be obtained, which induces a much enhanced fluorescent
      intensity from the dye coated hybrid nanostructures. Moreover, the graphene
      sheets covering completely and uniformly on the Cu NPs act as a passivation layer
      to protect the underlying metal surface from air oxidation. As a result, the
      stability of the LSPRs for the hybrid nanostructures is much enhanced compared to
      that of the bare Cu NPs. The transfer-free hybrid nanostructures with enhanced
      intensity and stability of the LSPRs will enable their much broader applications
      in photonics and optoelectronics.

PMID- 27872495
TI  - Association of TNFSF4 Polymorphisms with Vogt-Koyanagi-Harada and Behcet's
      Disease in Han Chinese.
AB  - To investigate whether single nucleotide polymorphisms (SNPs) of the Tumor
      Necrosis Factor Superfamily 4 (TNFSF4) gene are associated with Vogt-Koyanagi
      Harada (VKH) and Behcet's disease (BD) in a Chinese Han population. A two-stage
      case control study was carried out in 1331 VKH, 938 BD and 1752 healthy controls.
      Ten TNFSF4 SNPs, including rs1234314, rs1234315, rs2205960, rs704840, rs2795288,
      rs844654, rs12039904, rs10912580, rs844665, and rs844644, were genotyped using
      the PCR-restriction fragment length polymorphism method. Genotype and allele
      frequencies were analyzed between cases and healthy controls using the X2 or
      Fisher's exact test and p values were corrected for multiple comparisons. We
      observed a significantly increased frequency of the TT genotype of rs1234315 in
      BD patients (Pc = 1.44 * 10-5, OR = 1.734, 95% CI = 1.398-2.151). The frequency
      of the TT genotype of rs12039904 was significantly higher in patients with VKH
      disease as compared to controls (Pc = 4.62 * 10-5, OR = 1.959, 95% CI = 1.483
      2.588). Analysis of clinical manifestations in VKH disease and BD did not show an
      association with the TNFSF4 gene polymorphisms. The study suggests that the
      TNFSF4 gene may be involved in the susceptibility to VKH disease and BD in Han
      Chinese.

PMID- 27872498
TI  - The cryptic IRF2BP2-RARA fusion transforms hematopoietic stem/progenitor cells
      and induces retinoid-sensitive acute promyelocytic leukemia.

PMID- 27872497
TI  - Bcl-2 protein family expression pattern determines synergistic pro-apoptotic
      effects of BH3 mimetics with hemisynthetic cardiac glycoside UNBS1450 in acute
      myeloid leukemia.

PMID- 27872496
TI  - Inactivation of KLF4 promotes T-cell acute lymphoblastic leukemia and activates
      the MAP2K7 pathway.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological
      malignancy with a high incidence of relapse in pediatric ALL. Although most T-ALL
      patients exhibit activating mutations in NOTCH1, the cooperating genetic events
      required to accelerate the onset of leukemia and worsen disease progression are
      largely unknown. Here, we show that the gene encoding the transcription factor
      KLF4 is inactivated by DNA methylation in children with T-ALL. In mice, loss of
      KLF4 accelerated the development of NOTCH1-induced T-ALL by enhancing the G1-to-S
      transition in leukemic cells and promoting the expansion of leukemia-initiating
      cells. Mechanistically, KLF4 represses the gene encoding the kinase MAP2K7. Our
      results showed that in murine and pediatric T-ALL, loss of KLF4 leads to aberrant
      activation of MAP2K7 and of the downstream effectors JNK and ATF2. As a proof-of
      concept for the development of a targeted therapy, administration of JNK
      inhibitors reduced the expansion of leukemia cells in cell-based and patient
      derived xenograft models. Collectively, these data uncover a novel function for
      KLF4 in regulating the MAP2K7 pathway in T-ALL cells, which can be targeted to
      eradicate leukemia-initiating cells in T-ALL patients.

PMID- 27872499
TI  - Phosphatase PRL2 promotes oncogenic NOTCH1-Induced T-cell leukemia.

PMID- 27872501
TI  - SYNCHRONIZATION OF HETEROGENEOUS OSCILLATORS UNDER NETWORK MODIFICATIONS:
      PERTURBATION AND OPTIMIZATION OF THE SYNCHRONY ALIGNMENT FUNCTION.
AB  - Synchronization is central to many complex systems in engineering physics (e.g.,
      the power-grid, Josephson junction circuits, and electro-chemical oscillators)
      and biology (e.g., neuronal, circadian, and cardiac rhythms). Despite these
      widespread applications-for which proper functionality depends sensitively on the
      extent of synchronization-there remains a lack of understanding for how systems
      can best evolve and adapt to enhance or inhibit synchronization. We study how
      network modifications affect the synchronization properties of network-coupled
      dynamical systems that have heterogeneous node dynamics (e.g., phase oscillators
      with non-identical frequencies), which is often the case for real-world systems.
      Our approach relies on a synchrony alignment function (SAF) that quantifies the
      interplay between heterogeneity of the network and of the oscillators and
      provides an objective measure for a system's ability to synchronize. We conduct a
      spectral perturbation analysis of the SAF for structural network modifications
      including the addition and removal of edges, which subsequently ranks the edges
      according to their importance to synchronization. Based on this analysis, we
      develop gradient-descent algorithms to efficiently solve optimization problems
      that aim to maximize phase synchronization via network modifications. We support
      these and other results with numerical experiments.

PMID- 27872503
TI  - Harmonisation and What's in a Unit?

PMID- 27872502
TI  - The Communities That Care Brief Depression Scale: Psychometric Properties and
      Criterion Validity.
AB  - For community-level approaches to preventing depression, measures of depression
      that are brief as well as valid are needed, particularly given competing demands
      in surveys for assessment of other outcomes including substance use, delinquency,
      and their associated risk factors. This study examined the validity of a four
      item adolescent depression measure, the Communities That Care Brief Depression
      Scale (CTC-BDS). Data were from a survey of adolescents (N = 3,939) participating
      in the Community Youth Development Study (CYDS), a community-randomized trial
      involving 24 U.S. towns. The Patient Health Questionnaire nine-item (PHQ-9) was
      the criterion standard used to define major depressive disorder (MDD).
      Sensitivity and specificity of the CTC-BDS were both > .8 at a cutpoint of 6 and
      the area under the receiver operating characteristic curve was .91. Its strong
      psychometric properties and brevity make the CTC-BDS a useful measure for
      communities to monitor levels of youth depression.

PMID- 27872504
TI  - Harmonising Reference Intervals for Three Calculated Parameters used in Clinical
      Chemistry.
AB  - For more than a decade there has been a global effort to harmonise all phases of
      the testing process, with particular emphasis on the most frequently utilised
      measurands. In addition, it is recognised that calculated parameters derived from
      these measurands should also be a target for harmonisation. Using data from the
      Aussie Normals study we report reference intervals for three calculated
      parameters: serum osmolality, serum anion gap and albumin-adjusted serum calcium.
      The Aussie Normals study was an a priori study that analysed samples from 1856
      healthy volunteers. The nine analytes used for the calculations in this study
      were measured on Abbott Architect analysers. The data demonstrated normal
      (Gaussian) distributions for the albumin-adjusted serum calcium, the anion gap
      (using potassium in the calculation) and the calculated serum osmolality (using
      both the Bhagat et al. and Smithline and Gardner formulae). To assess the
      suitability of these reference intervals for use as harmonised reference
      intervals, we reviewed data from the Royal College of Pathologists of
      Australasia/Australasian Association of Clinical Biochemists (RCPA/AACB) bias
      survey. We conclude that the reference intervals for the calculated serum
      osmolality (using the Smithline and Gardner formulae) may be suitable for use as
      a common reference interval. Although a common reference interval for albumin
      adjusted serum calcium may be possible, further investigations (including a
      greater range of albumin concentrations) are needed. This is due to the bias
      between the Bromocresol Green (BCG) and Bromocresol Purple (BCP) methods at lower
      serum albumin concentrations. Problems with the measurement of Total CO2 in the
      bias survey meant that we could not use the data for assessing the suitability of
      a common reference interval for the anion gap. Further study is required.

PMID- 27872505
TI  - Harmonisation of Osmolal Gap - Can We Use a Common Formula?
AB  - Osmolal gap is the difference between the measured osmolality and a calculated
      osmolality based on the major commonly measured osmotically active particles. The
      perceived gap indicates the presence of unmeasured osmotically active particles.
      The major use of osmolal gap today is to screen for the possible presence of
      exogenous toxic substances in patients in an emergency department or intensive
      care unit. There is a long history of osmolal gap calculations and it needs to be
      appreciated that the uncertainty of the osmolal gap will be determined by the sum
      of errors in the calculated osmolality, error in measured osmolality and
      variability in unmeasured analytes. Since 1958 there has been a constant trickle
      of papers proposing both simple and sophisticated formulae to calculate the
      'ultimate' osmolal gap. A gap as close to zero as possible and with a low
      coefficient of variation across multiple clinical conditions and analytical
      platforms are also determinants of 'fitness for purpose' of any osmolal gap
      calculations. The Smithline-Gardner formula for calculated osmolality [2(Na) +
      Glu + Urea] is fit for purpose in both normal people and general hospital
      patients. It also performs well across different analytical platforms. This
      simple formula can be used for rapid mental calculation at the bedside and
      automated laboratory information system reporting whenever a measured osmolality
      is requested. In this era of harmonisation, we propose that this formula be
      adopted by all clinicians and laboratories.

PMID- 27872506
TI  - Harmonising Adult Reference Intervals in Australia and New Zealand - the
      Continuing Story.
AB  - Reference intervals (RIs) are used to help clinicians determine if a patient can
      be classified as being in a diseased or healthy state and there are often sound
      scientific and clinical reasons for differences in RIs. One of the current
      strategic priorities for the Australasian Association of Clinical Biochemists is
      to encourage and assist laboratories to achieve harmonisation of RIs for common
      clinical chemistry analytes where sound calibration and traceability are in
      place. This need is based on good laboratory practice, providing the clinician
      with results that allow appropriate and reliable clinical interpretation and
      progression further toward the national e-health framework and a single
      electronic health record. After reviewing and considering studies related to bias
      as well as both a priori and a posteriori RI studies nationally and
      internationally and the consideration of flagging rates and clinical relevance,
      an initial group of 12 harmonised RIs were endorsed by the Royal College of
      Pathologists of Australasia in 2014. In 2015, after further stakeholder
      consultation, a second group of six harmonised RIs for common chemistry analytes
      has been proposed for adults which includes ALT and AST where methods do not use
      pyridoxal-5'-phosphate as an activator and lipase excluding the Ortho Clinical
      Diagnostics and Siemens Dimension assays.

PMID- 27872507
TI  - Calculated Chemistry Parameters - do they need to be harmonised?
AB  - In clinical chemistry, harmonisation of the testing process is a global
      initiative with the purpose of improving patient safety, allowing better
      integration of research data and enabling the use of national electronic heath
      records. In Australia, as in other countries, the initial focus has been on the
      harmonisation of the more commonly measured analytes. There are also a number of
      calculated parameters, derived from these measured analytes, which could also be
      considered for harmonisation. Calculated parameters that are reported by
      laboratories and used for clinical decision-making should undergo the same robust
      process of harmonisation as is the case for the measured analytes. Aspects that
      should be considered for harmonisation are: terminology, the formulae used and
      where possible the use of common reference intervals. To investigate pathways
      towards the harmonisation of calculated parameters, three commonly reported
      parameters are considered. Calculated osmolality, the anion gap and albumin
      adjusted calcium are all derived from common analytes which have individually
      been considered for harmonisation. They present different methodological,
      measurement uncertainty and terminological hurdles to harmonisation and are
      likely to require different pathways and solutions.

PMID- 27872508
TI  - Hidden diversity in Thyridaria and a new circumscription of the Thyridariaceae.
AB  - A multigene analysis of a combined ITS-LSU-SSU-rpb2-tef1 sequence data matrix was
      applied to infer the phylogenetic position of the genus Thyridaria in the
      Pleosporales. The generic type of Thyridaria, T. broussonetiae (syn. T.
      incrustans), is situated in a clade currently named Roussoellaceae, which becomes
      a synonym of Thyridariaceae. However, Thyridaria rubronotata does not belong to
      this clade, but is here recognised as Cyclothyriella rubronotata in its own
      family Cyclothyriellaceae. The Thyridariaceae contain the genera Thyridaria,
      Roussoella, Roussoellopsis, Neoroussoella and the new genus Parathyridaria.
      Roussoella acaciae is combined in Thyridaria and Roussoella percutaenea in
      Parathyridaria. Ohleria modesta and an additional new thyridaria-like genus,
      Hobus, are found to represent isolated lineages with unresolved phylogenetic
      affinites within the Pleosporales. For Ohleria the new family Ohleriaceae is
      established. Melanomma fuscidulum belongs to Nigrograna, and three new species
      are described in this genus. A strain named Biatriospora marina clusters with
      Nigrograna. Based on the newly recognised species in Nigrograna, morphology and
      ecology do in no way correlate among these genera, therefore we erect the new
      family Nigrogranaceae for Nigrograna and recommend to discontinue the use of the
      family name Biatriosporaceae until fresh material of B. marina becomes available
      for sequencing.

PMID- 27872509
TI  - Diagnostic Utility of ANG in Coronary Heart Disease Complicating Chronic Heart
      Failure: A Cross-Sectional Study.
AB  - Angiogenin (ANG) has been shown to be elevated in several cardiovascular
      diseases. To detect its levels and diagnostic capacity in coronary heart disease
      (CHD) patients complicating chronic heart failure (CHF), we performed this cross
      sectional study and enrolled 616 CHD patients and 53 healthy controls. According
      to complicating CHF or not, the patients were divided into CHF group (n = 203)
      and CHD disease controls (n = 413), in which the CHF group was subdivided as
      heart failure with reduced ejection fraction (HFrEF) group or heart failure with
      preserved ejection fraction (HFpEF) group on the basis of left ventricular
      ejection fraction (LVEF), or as different NYHA class group. Their plasma ANG
      levels were detected using enzyme-linked immunosorbent assay (ELISA). Plasma ANG
      was 342.8 (IQR [273.9,432.9]), 304.5 (IQR [254.0,370.5]), and 279.7 (IQR
      [214.4,344.0]) ng/mL in the CHF group, CHD disease controls, and healthy
      controls, respectively, significantly higher in the CHF group compared with the
      others. Furthermore, among CHF group, ANG is dramatically higher in the HFrEF
      patients compared with the HFpEF patients. As for the diagnostic capacity of ANG,
      the area under the receiver operating characteristic curve was 0.71 (95% CI 0.63
      0.78). We concluded that plasma ANG is elevated in CHD complicating CHF patients
      and may be a moderate discriminator of CHF from CHD or the healthy.

PMID- 27872511
TI  - Synthesis of Trifluoromethoxylated (Hetero)Arenes via OCF3 Migration.
AB  - Incorporation of the OCF3 group into organic molecules, especially aromatic and
      heteroaromatic compounds, is recognized as one of the major challenges in
      synthetic organic chemistry. Although many attempts have been made to develop
      efficient trifluoromethoxylation strategies, most of the current approaches still
      require use of highly toxic, thermally unstable reagents, or impractical reaction
      conditions. Herein, we highlight a recent contribution from our group towards the
      synthesis of (hetero)aryltrifluoromethyl ethers. Our protocol is scalable,
      operationally simple, and allows an easy access to a wide range of synthetically
      useful ortho-OCF3 aniline derivatives, as well as functionalized
      trifluoromethoxylated pyridines and pyrimidines under mild reaction conditions.

PMID- 27872510
TI  - Association of the Aspartate Aminotransferase to Alanine Aminotransferase Ratio
      with BNP Level and Cardiovascular Mortality in the General Population: The
      Yamagata Study 10-Year Follow-Up.
AB  - Background. Early identification of high risk subjects for cardiovascular disease
      in health check-up is still unmet medical need. Cardiovascular disease is
      characterized by the superior increase in aspartate aminotransferase (AST) to
      alanine aminotransferase (ALT). However, the association of AST/ALT ratio with
      brain natriuretic peptide (BNP) levels and cardiovascular mortality remains
      unclear in the general population. Methods and Results. This longitudinal cohort
      study included 3,494 Japanese subjects who participated in a community-based
      health check-up, with a 10-year follow-up. The AST/ALT ratio increased with
      increasing BNP levels. And multivariate logistic analysis showed that the AST/ALT
      ratio was significantly associated with a high BNP (>=100 pg/mL). There were 250
      all-cause deaths including 79 cardiovascular deaths. Multivariate Cox
      proportional hazard regression analysis revealed that a high AST/ALT ratio (>90
      percentile) was an independent predictor of all-cause and cardiovascular
      mortality after adjustment for confounding factors. Kaplan-Meier analysis
      demonstrated that cardiovascular mortality was higher in subjects with a high
      AST/ALT ratio than in those without. Conclusions. The AST/ALT ratio was
      associated with an increase in BNP and was predictive of cardiovascular mortality
      in a general population. Measuring the AST/ALT ratio during routine health check
      ups may be a simple and cost-effective marker for cardiovascular mortality.

PMID- 27872512
TI  - A Systematic Review of Research on Autism Spectrum Disorders in Sub-Saharan
      Africa.
AB  - The burden of autism spectrum disorders (ASDs) in sub-Saharan Africa (SSA) is not
      well known. We carried out a systematic review of the literature to identify
      published work from SSA. We have systematically searched four databases, namely,
      Medline, PsycINFO, CINAHL, and Child Development & Adolescent Studies, through
      EBSCO and identified studies from across SSA. Based on predefined inclusion
      criteria, 47 studies were included in this review. Most of the identified studies
      (74%) were conducted in only 2 African countries, that is, South Africa and
      Nigeria. Additionally, most of these studies (83%) were carried out in the last
      decade. These studies had four major themes: development of measurement tools of
      ASD in Africa, examining the prevalence of ASD, identifying risk factors and risk
      markers, and examining psychosocial issues. We identified only a single
      population level study aimed at documenting the prevalence of ASD and could not
      identify a single case-control study aimed at examining a comprehensive set of
      potential risk factors. All intervention studies were based on very small sample
      sizes. Put together, our findings suggest that current evidence base is too
      scanty to provide the required information to plan adequately for effective
      intervention strategies for children with ASD in Africa.

PMID- 27872513
TI  - Vaginal Lactoferrin Modulates PGE2, MMP-9, MMP-2, and TIMP-1 Amniotic Fluid
      Concentrations.
AB  - Inflammation plays an important role in pregnancy, and cytokine and matrix
      metalloproteases (MMPs) imbalance has been associated with premature rupture of
      membranes and increased risk of preterm delivery. Previous studies have
      demonstrated that lactoferrin (LF), an iron-binding protein with anti
      inflammatory properties, is able to decrease amniotic fluid (AF) levels of IL-6.
      Therefore, we aimed to evaluate the effect of vaginal LF administration on
      amniotic fluid PGE2 level and MMP-TIMP system in women undergoing genetic
      amniocentesis. One hundred and eleven women were randomly divided into controls
      (n = 57) or treated with LF 4 hours before amniocentesis (n = 54). Amniotic fluid
      PGE2, active MMP-9 and MMP-2, and TIMP-1 and TIMP-2 concentrations were
      determined by commercially available assays and the values were normalized by AF
      creatinine concentration. PGE2, active MMP-9, and its inhibitor TIMP-1 were lower
      in LF-treated group than in controls (p < 0.01, p < 0.005, and p < 0.001, resp.).
      Conversely, active MMP-2 (p < 0.0001) and MMP-2/TIMP-2 molar ratio (p < 0.001)
      were increased, whilst TIMP-2 was unchanged. Our data suggest that LF
      administration is able to modulate the inflammatory response following
      amniocentesis, which may counteract cytokine and prostanoid imbalance that leads
      to abortion. This trial is registered with Clinical Trial number NCT02695563.

PMID- 27872514
TI  - The Role of Interleukin-17 in Lung Cancer.
AB  - Tumour-associated inflammation is a hallmark of malignant carcinomas, and lung
      cancer is a typical inflammation-associated carcinoma. Interleukin-17 (IL-17) is
      an important inflammatory cytokine that plays an important role in chronic
      inflammatory and autoimmune diseases and in inflammation-associated tumours.
      Numerous studies have shown that IL-17 directly or indirectly promotes tumour
      angiogenesis and cell proliferation and that it inhibits apoptosis via the
      activation of inflammatory signalling pathways. Therefore, IL-17 contributes to
      the metastasis and progression of lung cancer. Research advances with respect to
      the role of IL-17 in lung cancer will be presented as a review in this paper.

PMID- 27872515
TI  - Therapeutic Treatment of Arthritic Mice with 15-Deoxy Delta12,14-Prostaglandin J2
      (15d-PGJ2) Ameliorates Disease through the Suppression of Th17 Cells and the
      Induction of CD4+CD25-FOXP3+ Cells.
AB  - The prostaglandin, 15-deoxy Delta12,14-prostaglandin J2 (15d-PGJ2), is a lipid
      mediator that plays an important role in the control of chronic inflammatory
      disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well
      determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental
      model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of
      CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was
      associated with a marked reduction in joint levels of proinflammatory cytokines.
      Although the mRNA expression of ROR-gammat was profoundly reduced, FOXP3 was
      enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The
      specific and polyclonal CD4+ Th17 cell responses were limited during the addition
      of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the
      expression of FOXP3, GITR, and CTLA-4 in the CD4+CD25- population, suggesting the
      induction of Tregs on conventional T cells. Prostanoid addition to CD4+CD25-
      cells selectively suppressed Th17 differentiation and promoted the enhancement of
      FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of
      collagen-induced arthritis by regulating Th17 differentiation, concomitant with
      the induction of Tregs, and, consequently, protected mice from diseases
      aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a
      potential therapeutic strategy in RA.

PMID- 27872517
TI  - How does the brain keep information "in mind"?

PMID- 27872516
TI  - Proliferative Effects of Histamine on Primary Human Pterygium Fibroblasts.
AB  - Purpose. It has been confirmed that inflammatory cytokines are involved in the
      progression of pterygium. Histamine can enhance proliferation and migration of
      many cells. Therefore, we intend to investigate the proliferative and migratory
      effects of histamine on primary culture of human pterygium fibroblasts (HPFs).
      Methods. Pterygium and conjunctiva samples were obtained from surgery, and
      toluidine blue staining was used to identify mast cells. 3-[4, 5-Dimethylthiazol
      2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the
      proliferative rate of HPFs and human conjunctival fibroblasts (HCFs); ki67
      expression was also measured by immunofluorescence analysis. Histamine receptor-1
      (H1R) antagonist (Diphenhydramine Hydrochloride) and histamine receptor-2 (H2R)
      antagonist (Nizatidine) were added to figure out which receptor was involved.
      Wound healing model was used to evaluate the migratory ability of HPFs. Results.
      The numbers of total mast cells and degranulated mast cells were both higher in
      pterygium than in conjunctiva. Histamine had a proliferative effect on both HPFs
      and HCFs, the effective concentration (10 MUmol/L) on HPFs was lower than on HCFs
      (100 MUmol/L), and the effect could be blocked by H1R antagonist. Histamine
      showed no migratory effect on HPFs. Conclusion. Histamine may play an important
      role in the proliferation of HPFs and act through H1R.

PMID- 27872518
TI  - Spinal fusion surgery: A historical perspective.
AB  - The vast majority of technological advances in spinal fusion surgery have
      occurred within the past 50 years. Despite this, there existed a rich history of
      innovation, ingenuity, and resourcefulness among the spine surgeons of centuries
      before. Here, we pay tribute to this history, highlighting the important
      characters, their devices, and their thoughts, as they sought to alleviate human
      suffering from spinal deformity.

PMID- 27872520
TI  - Desk of the Editor.

PMID- 27872521
TI  - Comments on Radical Esophagectomy after Neoadjuvant Chemoradiation: Single
      Institutional Experience from Tertiary Cancer Centre in India.

PMID- 27872519
TI  - The inflatable intramedullary nail for humeral shaft fractures.
AB  - BACKGROUND: We assessed the results of humeral shaft fracture fixation using the
      inflatable intramedullary nail using radiological and clinical findings. METHODS:
      From 2012 to 2015, we treated 14 patients with humeral shaft fractures using
      inflatable intramedullary nail after closed reduction. RESULTS: The mean follow
      up time was 14.1 months. The mean time to bone union was 4.5 months. None of the
      patients had major perioperative mechanical complications or postoperative
      complications, except for the occurrence of fixation loss and non-union in one
      patient. CONCLUSION: Inflatable intramedullary nails seem to be applicable, safe
      and effective for humeral AO/OTA type A midshaft fractures.

PMID- 27872522
TI  - Sentinel Lymph Node Biopsy in N0 Neck for Squamous Cell Carcinoma of Oral Cavity:
      a Prospective Study.
AB  - Oral cancers in India are very common. SLNB (sentinel lymph node biopsy) for the
      management of the cN0 neck provides proper staging with less morbidity. The study
      aims at assessment of the technical feasibility and accuracy of SLNB. Two by two
      table and Kappa statistic was used to compare SLN and END. In 14 cases out of 16
      cases, SLN was identified. Sensitivity and specificity of 100 % were found. One
      hundred percent agreement was observed between SLN and END using kappa
      statistics. A meta-analysis of 19 studies showed 97.7 % sentinel node
      identification rate and 92.6 % sensitivity with a false negative rate of 3 %. In
      patients with N0 neck and negative SLN, neck dissection can be avoided decreasing
      morbidity of SOND. SLN biopsy has potential to become standard of care for
      managing N0 neck; however, long-term oncological results need to be evaluated.

PMID- 27872523
TI  - Impact of Molecular Predictors on the Response Rates in Head and Neck Cancer
      Patients - an Observational Study.
AB  - Squamous cell carcinoma of head and neck region account for more than 25 % of
      male and more than 10 % of female cancers in India (1). Head and neck cancer
      treatment includes a multidisciplinary approach involving all specialties.
      Concurrent chemo-radiation is the standard of care in most of the subsites (2).
      Inspite of the multi-disciplinary approach, a plateau has been reached in terms
      of results with 5 year survival of locally advanced disease of around 30 % (3).
      In order to improve outcomes, there has been considerable interest in molecular
      profiling of head and neck cancers 4-10. However there is still significant
      paucity in terms of Indian data, hence the need for the study. The objectives are
      to assess the HPV-p16, EGFR and p53 status, to correlate HPV-p16, EGFR and p53
      status with the response rates, to correlate HPV-p16,EGFR and p53 status with
      other factors like age, sex, tobacco use. Twenty five consecutive cases of
      histopathologically proven head and neck cancers were accrued. All patients were
      treated with external radiation to a dose of 66Gy in 33 fractions along with
      concurrent weekly cisplatin chemotherapy at a dose of 40mg/sqm. HPV-p16, EGFR and
      p53 mutation analysis was done on paraffin embedded histopathological blocks. PCR
      technique used for HPV-p16, EGFR and p53 status detection. Response assessment
      was done based on RECIST criteria. Correlation of HPV, EGFR and p53 status on
      response was done. The EGFR positivity rate was 84 %, the p53 positivity rate was
      76 % and the HPV p-16 positivity rate was 28 %. Out of 25 patients, 13(52%) had
      complete response, 7(28 %) had partial response, 3(12 %) had stable disease and
      2(8 %) had progressive disease. On correlation of molecular profile with
      response, there was no statistical significance between EGFR status and response
      (p 0.5) or HPV-p16 and response (p 0.8). However, p53 positivity was approaching
      significance with respect to good response (p 0.07).

PMID- 27872525
TI  - Experiences of Breast Cancer Survivors with Oncology Settings in Urban India:
      Qualitative Findings.
AB  - The experience of diagnosis and treatment of cancer leads to significant changes
      within an individual. In the course of survivorship trajectory, very often cancer
      survivors are left with the sense, improvements could be done to enhance the
      quality of cancer care. This article focuses on experiences of breast cancer
      survivors with oncology setting in urban India. Data was collected from 15 women
      in South and East India using in-depth interview method. Qualitative interview
      data was analysed using descriptive phenomenology method. Areas of importance
      that emerged broadly included informational and emotional categories. Findings
      reveal quality of cancer care in India can be improved through developing an
      orientation towards patient-centred style rather than doctor/disease centred
      approach which has major influence on physical and mental health outcomes. This
      would require further research and increased emphasis on training of medical as
      well as paramedical professionals.

PMID- 27872526
TI  - Progesterone Receptors, Pathological Complete Response and Early Outcome for
      Locally Advanced Breast Cancer - a Single Centre Study. (PPLB - 01).
AB  - Neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC), apart
      from increasing breast conservation rates, also provides an opportunity to assess
      tumour response to chemotherapy, with Pathological Complete Response (pCR)
      described as an independent prognostic factor and a surrogate marker for better
      outcome and survival. Our primary aim was to identify clinical and pathological
      factors associated with pCR following NACT in patients with LABC treated at our
      institution. Our secondary aim was to analyze the impact of pCR and associated
      factors on disease free survival (DFS) and overall survival (OS). A retrospective
      analysis of LABC patients treated with NACT between Jun 2011 and Dec 2013.
      Clinical and histological variables were analyzed for association with pCR (no
      invasive or in situ carcinoma in breast or axillary lymph nodes). Kaplan-Meier
      curves and Cox regression model was used for survival analysis. All values were
      twosided, and statistical significance was defined as p < 0.05. 240 patients were
      included. The median tumor size was 6 cm, with T4 disease in 49.8 %. 45 % of
      tumors were of low grade (G1 + G2) and 53.8 % of high grade (G3). Estrogen
      Receptor (ER) was positive in 70.8 %, progesterone receptor (PR) in 53.3 % and
      Her2 in 38.8 %. The preferred NACT regimen was sequential anthracycline and
      taxane and 88.8 % of patients received this regimen. Of 93 potential Her2
      Positive patients, only 23 received trastuzumab. Overall 23.2 % patients had pCR.
      At median follow up of 21 months (range, 3-42), 16.3 % of patients had recurrent
      disease, and 6.7 % had died. High tumor grade (p = 0.04), PR negative status (p <
      0.01) and trastuzumab treatment (p = 0.01) were significant predictors of pCR in
      univariate analysis. On multivariate analysis PR negativity (OR 3.2, 95 % CI =
      1.6 to 6.04, p = 0.001) and Trastuzumab use (OR 0.24, 95 % CI = 0.1 to 0.6, p =
      0.004) were significant. Patients with pCR had positive associations with
      survival (p < .02,OS& .02,DFS) and interestingly PR positivity had positive
      association with DFS (p = 0.02) in Kaplan-Meier curves. On Cox regression, PR
      positivity (HR = 0.3, p < 0.01) and pCR (HR = 0.2, p < 0.01) correlated with DFS,
      though not with early OS. for the PR positive patients were paradoxical. Though
      less likely to have pCR (15 %, vs 32 % if PR negative), they had better DFS (p =
      0.02), and achieving pCR had no survival benefit in this group. In contrast, PR
      negative patients, irrespective of ER status, had a high pCR rate, and achieving
      pCR had survival advantage (p < 0.05,DFS& p < 0.02,OS). PR negative patients
      without pCR had the worst DFS (p < 0.01) among all. High grade and Trastuzumab
      treatment as predictors of pCR, and pCR as a surrogate marker for survival are
      well recognized, and are supported by our findings. In present cohort, PR
      negativity showed prognostic importance independent of ER status. However these
      results were derived from sub-group, post-hoc analysis of data from a pre
      existing cohort, without 'a-priori' hypothesis for survival analysis in relation
      to PR. These "hypothesis generating" results need confirmation by a well-designed
      prospective cohort or a randomized trial.

PMID- 27872524
TI  - Human Papilloma Virus in Oral Cavity Cancer and Relation to Change in Quality of
      Life Following Treatment-a Pilot Study from Northern India.
AB  - Human papilloma virus (HPV)-associated head and neck cancer (HNC) has generated
      significant amount of research interest in recent times with focus shifted to
      oral cavity squamous cell cancer (OCSCC) after oropharyngeal cancer. Due to high
      incidence of OCSCC and anecdotal reports on association of HPV infection from
      northern region of India, this study was conceived to investigate HPV infection
      and establish its association with lifestyle habits such as tobacco, alcohol
      consumption, oro-genital sex, number of sexual contacts, and change in quality of
      life posttreatment. A total of 43 primary OCSCC biopsy specimens were collected.
      These samples were analyzed for HPV DNA genotyping which was done by using 13
      high-risk HPV real-time PCR kits. Quality of life was assessed using University
      of Washington questionnaire for HNC patients, which was administered pretreatment
      and 3-months posttreatment. HPV presence was confirmed in only three patients
      (7.0 %). HPV positivity did not find any statistical correlation with age,
      gender, residence, addiction habit, stage, tumor size, nodal status, tumor grade,
      and number of sexual contacts. There was no significant (p > 0.05) difference in
      the average percent change in QOL parameters from pretreatment to posttreatment
      when correlated with HPV status.

PMID- 27872527
TI  - Role of Axillary Ultrasound, Fine Needle Aspiration Cytology and Sentinel Lymph
      Node Biopsy in clinically N0 Breast Cancer.
AB  - This study evaluates the combined role of axillary ultrasound, fine needle
      aspiration cytology and sentinel lymph node biopsy in clinically N0 axilla.
      Between January 2014 and June 2015, 150 women with early breast cancer underwent
      axillary ultrasound as a first investigation for nodal status. Suspicious nodes
      were subjected to image guided fine needle aspiration cytology. Non-suspicious
      and fine needle aspiration cytology negative axillary nodes proceeded to sentinel
      lymph node biopsy at time of primary breast surgery. All confirmed positive
      (cytology and frozen) cases proceeded to axillary lymph node dissection. 52 women
      had positive axillary nodes at final histology. Axillary ultrasound with fine
      needle aspiration cytology identified 27 patients with positive axillary nodal
      status and had a sensitivity of 84.36 % (27/32) and specificity of 87.5 %
      (14/16). Intraoperative frozen analysis identified a further 13 cases with
      sensitivity of 56.52 % (13/23) and specificity of 97.56 % (80/82). Overall 76.92
      % (40/52) patients with positive axillary metastasis were identified peri
      operatively using combination of axillary ultrasound, cytology and sentinel lymph
      node biopsy.

PMID- 27872528
TI  - Evaluation of Surgical Outcomes of Oncoplasty Breast Surgery in Locally Advanced
      Breast Cancer and Comparison with Conventional Breast Conservation Surgery.
AB  - The purpose of this study was to compare early oncologic outcomes of oncoplastic
      breast surgery and conventional breast conservation surgery in patients of
      locally advanced breast cancer. A single-center, prospective, non-randomized
      study enrolled select cases of locally advanced breast cancer (TNM T3/T4, N0/1/2)
      who after neoadjuvant chemotherapy, were considered for breast conservation
      surgery with oncoplasty techniques. The specimen volume resected, the mean
      margins and mean closest margin obtained were noted. The re-surgery rates,
      complication rates, and incidence of locoregional recurrence were also noted.
      Variables were compared with a retrospective cohort of similar patients who had
      undergone conventional breast conservation surgery. Fifty-seven patients
      underwent OBS (group 1) and were compared with 43 cases that had undergone
      conventional BCS (group 2). Majority of the patients in group 1 (73 %) had cT3
      with N0 or N+ and a minority (17 %) were with limited skin involvement (cT4 and
      N0/N+). Relatively larger sized, post-NACT tumors could undergo OBS(4.4 vs 2.3
      cm). Relatively greater proportion of tumors in central and lower quadrants were
      addressed by oncoplasty than traditional BCS (17/57, 29 % vs 4/43, 9 %, p =
      0.04). The mean specimen volume excised in group 1 was more than that in group 2.
      (187.54 vs 125.19; p = 0.01). The mean of the margins were obtained more in group
      1 (1.04 vs 0.69 cm); p < 0.01) as also the mean closest margin (0.86 vs 0.49 cm;
      p < 0.01). The incidence of close or involved margins was lesser in the OBS group
      (8 vs 24 %). Overall incidence of complications was similar in both groups (8/57,
      14 % vs 4/43, 9 %; p = 0.34 NS). The median follow-up period of group 1 is 18
      months (range 06-30 months) while group 2 is 34 months (14-44 months. There was
      no recurrence in group 1, but there were 5 cases (11 %) in group 2. Oncoplasty
      breast surgery offers more opportunity for breast conservation and oncologic
      safety than conventional breast conserving surgery.

PMID- 27872529
TI  - Oncological Safety of Submental Artery Island Flap in Oral Reconstruction -
      Analysis of 229 Cases.
AB  - Submental artery island flap (SMIF) is gaining popularity as a viable alternative
      to free flaps in carefully selected oral cavity defects after surgical
      extirpation of cancers.The current paper looks into the overall efficacy and
      oncological safety of the flap based on a prospective audit of 229 cases done at
      a high volume cancer center from october 2004 to september 2012 and concludes
      that SMIF is a oncologically safe,reliable reconstructive option in carefully
      selected oral cancers undergoing surgical resections.

PMID- 27872530
TI  - Deep Vein Thrombosis in Indian Cancer Patients Undergoing Major Thoracic and
      Abdomino-Pelvic Surgery.
AB  - The aim of the study was to determine the incidence of postoperative deep vein
      thrombosis (DVT) in Indian patients undergoing surgery for thoracic and abdomino
      pelvic malignancies. A prospective observational study was conducted in a
      tertiary care cancer centre in North India. Two hundred and fifty consecutive
      patients who underwent curative surgery for thoracic and abdomino-pelvic
      malignancies during the period March 2014 to March 2015 were enrolled in the
      study. Perioperative pharmacological antithrombotic prophylaxis was not
      prescribed to any of the patient as per the institutional protocol. All the
      patients underwent colour duplex ultrasound of the bilateral lower limbs -
      preoperatively to determine the baseline status, and on 7th and 28th day
      postoperatively to look for presence of DVT. None of the patient in the study
      cohort showed clinical or radiological evidence of lower limb deep vein
      thrombosis. Our study suggests very low incidence of deep vein thrombosis in
      Indian patients undergoing surgery for thoracic and abdomino-pelvic malignancy.

PMID- 27872531
TI  - Positive Peritoneal Lavage Cytology -Implications for Staging and Management of
      Gastric Cancer.
AB  - The survival rates of gastric cancer patients with cytology-positive peritoneal
      lavage fluid without macroscopic dissemination (CY+/P-) is the same as that of
      patients with overt peritoneal metastasis.The 5-year survival rate of such
      patients is only 2%. The current study aims to highlight its significance in the
      staging of gastrointestinal malignancies and its implications for patient care.
      Prospective nonrandom analysis of peritoneal wash cytology in patients with
      gastrointestinal malignancies was conducted in the department of Surgical
      Gastroenterology, Nizams Institute of Medical Sciences, Hyderabad from January
      2012 to June 2013. Descriptive statistics and ANOVA variance analysis was
      performed to estimate incidence, risk factors and the effect of surgery in
      causing peritoneal dissemination of malignancy. A total of 60 patients with
      operable gastric cancer underwent peritoneal lavage for evaluation of malignant
      cells. The incidence of Positive peritoneal lavage cytology was 8.3% (5/60).Four
      patients with positive lavage fluid belong to T3 stage (11.7%, p-0.309).Poorly
      differentiating and mucinous tumors had a higher incidence of positive cytology
      (18.1% and 25%).None of the patients with positive cytology had positive
      resection margin. Tumors with advanced T stage, lymph nodal involvement, lympho
      vascular and perineural invasion have higher incidence of positive peritoneal
      cytology. Surgical handling has a negligible effect in peritoneal dissemination
      of tumor. Large scale studies are warranted to validate the findings and define
      it's role in management of gastric cancer.

PMID- 27872532
TI  - Presentation and Management of Inguinal Lymphadenopathy in Ovarian Cancer.
AB  - The symptoms in ovarian cancer are often missed leading to dubious diagnosis and
      staging. Inguinal lymphadenopathy (ILAP) is reported to be rare and occurring via
      lymphatic or hematogenous route. The paucity of studies on ILAP in ovarian cancer
      indicates a scope of refining its staging and management. The present study aims
      to document the presentation and management of ILAP in ovarian cancer, which may
      also reflect its incidence and mechanism of spread. All patients of ovarian
      cancer with inguinal lymphadenopathy presenting to our institute from 1 January
      2015 to 31 December 2015 were included. All clinical, treatment, and pathological
      details were analyzed. Seven patients of ovarian cancer presented with ILAP. The
      mean age and BMI were 53.29 +/- 8.38 years and 26.23 +/- 3.03 kg/m2. Presentation
      varied from advanced disease (adnexal, omental, peritoneal, and nodal) to
      isolated ILAP even without adnexal mass (n = 4). Mean CA 125 was 229.64 +/- 322
      (20-924) and ovarian primary was confirmed on microscopy or immunohistochemistry.
      Six patients underwent surgery with (n = 4) or without neoadjuvant chemotherapy
      (n = 2). Complete cytoreduction could be achieved in all patients with acceptable
      operative and perioperative outcomes. Peritoneal surface spread, along hernia
      track to the groin, was seen in two patients. Histopathology showed advanced
      disease, isolated ILAP and no residual disease in 3, 2, and 1 patient,
      respectively. ILAP has diverse clinical presentation in ovarian cancers and is
      not that uncommon. ILAP may also occur by peritoneal surface spread and shows
      good results with cytoreductive surgery and chemotherapy.

PMID- 27872534
TI  - Use of Combined PMMC and Nasolabial Flap for Reconstruction of Full Thickness
      Cheek Defect Involving Lip Commisure.
AB  - Head neck cancer constitute significant cancer burden and among it carcinoma of
      oral cavity involving buccal mucosa is most common entity in India. Very often it
      involves lip commisure. Radical surgery along with radiotherapy still remains
      treatment of choice. Reconstruction of composite defect of oral cavity fallowing
      ablative surgery remains difficult task. Reconstruction of lip commisure defect
      after primary tumor excision is still a big challenge. Micro vascular technique
      primary repair is main modality of treatment which needs great surgical expertise
      in plastic surgery which is not possible in every institution. We propose a novel
      surgical reconstructive technique of use of combine pectoralis major myocutaneous
      flap (PMMC) with nasolabial flap for full thickness cheek defect involving large
      lip commisure. Both flaps having distinct advantage of relative ease in elevating
      flap and robust vascularity with acceptable aesthetic and functional outcome.

PMID- 27872535
TI  - Femoral Arterial Blowout Post Groin Recurrence in Vulvar Carcinoma - Novel
      Endovascular Management.

PMID- 27872536
TI  - Phrenic Nerve Palsy as Initial Presentation of Large Retrosternal Goitre.
AB  - Unilateral phrenic nerve palsy as initial presentation of the retrosternal goitre
      is extremely rare event. This is a case report of a 57-year-old woman with
      history of cough and breathlessness of 3 months duration, unaware of the thyroid
      mass. She had large cervico-mediastinal goiter and chest radiograph revealed
      raised left sided hemidiaphragm. Chest CT scan did not reveal any lung
      parenchymal or mediastinal pathology. The patient underwent a total thyroidectomy
      through a cervical approach. The final pathology was in favor of multinodular
      goitre. Even after 1 year of follow up, phrenic nerve palsy did not improve
      indicating permanent damage. Phrenic nerve palsy as initial presentation of the
      retrosternal goitre is unusual event. This case is reported not only because of
      the rare nature of presentation, but also to make clinicians aware of the entity
      so that early intervention may prevent attendant morbidity.

PMID- 27872533
TI  - Role of Imaging in Peritoneal Surface Malignancies.
AB  - Imaging plays a vital role in the evaluation of peritoneal malignancies. The
      presence of peritoneal metastases (PM) alters tumor staging, with direct
      implications in treatment choice and prognosis. Cytoreductive surgery (CRS) and
      Hyperthermic intraperitoneal chemotherapy (HIPEC) as a combined modality
      treatment have led to prolonged survival and even cure in selected patients with
      PM. Better outcomes are seen in patients with limited disease spread. Therefore,
      early diagnosis of peritoneal tumor seeding is essential. Despite significant
      advancement of technology, assessment of the origin of PM is often difficult, due
      partly to the complex peritoneal anatomy and partly due to the complex overlap of
      imaging features. Multidetector CT (MDCT) is the main stay due to its wide
      availbility, rapid evaluation, robust technique and good resolution. Imaging
      plays a vital role in selecting patients for the combined modality treatment. MRI
      is not as popular as CT due to limited availability, time required for the study
      and lack of experience with interpreting the results. PET-CT is useful in ruling
      out extra peritoneal disease and it is the CT component that is more reliable for
      predicting the disease extent. This article reviews the current use of various
      imaging modalities in various stages of treatment of patients with PM especially
      those undergoing CRS and HIPEC.

PMID- 27872537
TI  - Large Retroperitoneal Extraosseous Osteosarcoma Invading into the Spine: a Case
      Report.
AB  - Extraosseous osteogenic sarcoma is a very rare malignant neoplasm. The most
      common sites are the extremities, thorax, and the abdomen. Retroperitoneal
      osteosarcomas are rare and very few cases have been reported. They are similar in
      their biology to high-grade soft tissue sarcomas. R0 resection appears to be the
      best possible treatment for these tumors but there are no published cases on how
      to manage them when it involves posterior and intra-spinal regions. We report a
      62-year-old male who presented with a backache, and investigations revealed a
      large retroperitoneal fibrosarcoma invading into the lumbar spine, but was found
      to be an extra osseous osteosarcoma on final histopathological examination. It is
      important to emphasize that due to the rarity of soft tissue sarcomas as well as
      the uniqueness of the multimodal treatment plan for each subtype, soft tissue
      sarcomas involving the spine are best managed by a multi disciplinary team.
      Overall, patients with soft tissue sarcomas involving the spine usually present a
      poor long-term prognosis. Therefore, whenever feasible, "en bloc" resection of
      such lesions has been shown to play a crucial role in improving the overall and
      recurrence-free survival rates.

PMID- 27872538
TI  - Primary Squamous Cell Carcinoma of Thyroid - A Rare Malignant Goitre.
AB  - Primary squamous cell carcinoma of thyroid is a very rare malignant disease
      because thyroid gland lacks squamous cells. The disease is almost fatal. Only
      around 60 cases have been reported in literature. Its incidence is less than 1 %
      of all thyroid malignancies. The overall survival rate is less than 1 year after
      the diagnosis. Here we report a rare case of a 70 year old lady who presented
      with sudden increase in the size of swelling associated with pain and obstructive
      symptoms in long standing thyroid swelling. Considering patient's age and
      inoperable nature of disease we treated the patient with concurrent
      chemoradiation.

PMID- 27872539
TI  - Adenosquamous Carcinoma of the Duodenum: a Rare Entity.
AB  - Adenosquamous carcinomas (ASC) of the duodenum are extremely rare neoplasms. They
      have been reported throughout gastrointestinal tract, including the
      gastroesophageal junction and the anal canal. Only a few cases of ASC of the
      small bowel and duodenum have been reported in the literature. Here in we report
      a case ASC of the second part of the duodenum in a 78-year-old man.

PMID- 27872540
TI  - Glomangiopericytoma Versus Solitary Fibrous Tumor: an Omental Tumor with Unusual
      Diagnostic Dilemma.

PMID- 27872541
TI  - Splenic Metastasis from Cancer of Uterine Cervix-a Rare Case.
AB  - Cancer of uterine cervix is one of the most common malignancies in women.
      Metastatic recurrence of cervical cancer in spleen is rare, mostly seen in
      autopsies. Splenic metastasis from cervical cancer in a living patient without
      disseminated metastases is rarer. Here, we present the case of a lady aged 46
      years with cervical cancer-squamous cell carcinoma-who had undergone radical
      hysterectomy and postoperative 50 Gy of intensity modulated radiation therapy in
      25 fractions and 50 mg of weekly cisplatin for 6 weeks. She was doing well for 17
      months. Then, she developed fever and anorexia, and was detected to have splenic
      lesion and a lesion in the pelvic mesentery in PET/CT (positron emission
      tomography-computed tomography). Laparoscopy showed enlarged spleen with a mass
      lesion and a mass in ileal mesentery adherent to the peritoneum over the fundus
      of bladder and greater omentum. She underwent resection of a segment of ileum
      with the mesenteric lesion and omentum and bladder peritoneum laparoscopically
      and splenectomy. Histopathological examination revealed both the mesenteric and
      splenic lesions to be metastases from poorly differentiated carcinoma, which was
      from the cervical cancer. Immunohistochemistry was suggestive of squamous cell
      carcinoma associated with high-risk human papilloma virus. After the
      postoperative recovery, patient was started on ciplatin with paclitaxel
      chemotherapy.

PMID- 27872542
TI  - Pulmonary Lymphomatoid Granulomatosis- a Case Report with Review of Literature.
AB  - Lymphomatoid granulomatosis is a rare, Epstein Barr Virus (EBV)-associated
      systemic angiodestructive disorder that may progress to a diffuse large B cell
      lymphoma. Pulmonary involvement occurs in over 90 % cases followed by kidney,
      skin and brain. WHO classifies lymphomatoid granulomatosis under the generic
      heading of B cell proliferations of uncertain malignant potential.
      Radiologically, pulmonary lymphomatoid granulomatosis (PLG) presents with non
      specific findings making histopathology the gold standard for diagnosis. The
      histological diagnosis of PLG includes a triad of polymorphic lymphoid
      infiltrates, transmural infiltration of arteries and veins by lymphoid cells
      ("angiitis"), and focal areas of necrosis within the lymphoid infiltrates. PLG
      should be distinguished from granulomatosis with polyangitis, as well as other
      forms of malignant lymphoma, like extranodal NK/T cell lymphoma, secondary
      diffuse large B-cell lymphoma and primary Non Hodgkin lymphomas of lung.

PMID- 27872543
TI  - Extra Mammary Paget's Disease of Vulva-a Case Report.
AB  - Extra mammary Paget's disease (EMPD) is a rare condition involving the vulva,
      anogenital region, and axilla. Vulvar disease usually presents as a slow growing
      well-defined itchy plaque with crustations or ulcerations over the affected area
      in postmenopausal women. Well-established guidelines for diagnosis and management
      are not available for this rare condition. Our patient is a 64-year-old
      postmenopausal woman with a history of similar complaints of 2 years duration,
      not responding to multiple topical treatments. She was diagnosed with EMPD on
      incisional biopsy and treated with surgery at our centre.

PMID- 27872544
TI  - Breast Lumps That Do Not Arise from the Breast.
AB  - An elderly lady presented to the surgical outpatient with a lump in her breast.
      On examination, there was a well-defined large lump measuring about 12 * 10 cm,
      hard in consistency and fixed to the chest wall, the skin appeared to be free,
      and the nipple-areola complex was normal. A provisional diagnosis of phylloides
      tumor was made, but digital rectal examination revealed a circumferential rectal
      growth. To our surprise, biopsy of the rectal growth and the chest wall mass
      revealed similar adenocarcinoma cells. This image illustrates the possibility
      that a common clinical entity such as a breast lump can sometimes surprise even
      the most seasoned clinicians.

PMID- 27872545
TI  - How effective the problem-based learning (PBL) in dental education. A critical
      review.
AB  - The purpose of this critical review is to explore the research supporting the
      effectiveness of problem-based learning (PBL) as a teaching method in dental
      education. PBL was developed more than 40 years ago in reaction to the problems
      and limitations of traditional teaching approaches. Here, aspects of the PBL
      teaching approach are reviewed, and the reasons for the substantial effect of
      this approach on dental education are discussed. Evidence shows that students in
      PBL-based courses exhibit superior professional skills and effective learning
      compared with those instructed using traditional approaches.

PMID- 27872546
TI  - Evaluation of root canal morphology of maxillary second premolars in a Saudi
      Arabian sub-population: An in vitro microcomputed tomography study.
AB  - AIM: To investigate the root canal morphology of maxillary second premolars in a
      Saudi Arabian subpopulation using microcomputed tomography (micro-CT).
      METHODOLOGY: Micro-CT analysis was performed on 100 maxillary second premolars.
      The anatomy of each tooth (number of roots, canals, orifices, and apical
      foramina, and the presence of apical deltas and accessory canals) was analyzed
      from reconstructed three-dimensional images. RESULTS: The most common morphology
      was a single root (67%), followed by two roots (30%), and three roots (3%).
      Regarding the canal morphology, most teeth (65%) contained two canals, followed
      by 30% with one canal, and 5% with three canals. One orifice was observed in 55%
      of teeth, and two orifices were detected in 45% of teeth. According to the
      Vertucci classification, the most common canal types were IV and V (both found in
      23% of teeth), followed by type I (17%), type III (9%), type II (7%), and type
      VII (2%). Additional types that were inconsistent with the Vertucci
      classification were recorded in 19% of teeth. CONCLUSION: The root canal
      morphology of maxillary second premolars in the Saudi Arabian subpopulation is
      complex and requires cautious evaluation prior to endodontic treatment.

PMID- 27872547
TI  - Measuring dental students' preference: A comparison of light microscopy and
      virtual microscopy as teaching tools in oral histology and pathology.
AB  - OBJECTIVES: Light microscopy used to be the traditional modality of teaching
      histology and pathology disciplines. Recent advances and innovations in the
      information technology field have revolutionized the use of hard- and software in
      medical education. An example of such an innovation is the so-called virtual
      microscopy. Many schools have started to adopt virtual microscopy as a new method
      aimed at enhancing student learning. Nonetheless, few reports have described the
      experiences of introducing virtual microscopy in dental education. We conducted
      this study to evaluate student perceptions of virtual microscopy use. MATERIALS
      AND METHODS: A survey of 9 items with a five-point Likert scale was designed to
      assess student perceptions of different aspects of virtual microscopy use
      compared with light microscopy. Eighty-seven 2nd year dental students answered
      the survey for a response rate of 80%. RESULTS: The majority of the students
      (85.1%) reported positive feedback for the use of virtual slides as a method of
      learning. Students reported significantly higher scores in virtual microscopy
      compared with light microscopy (t test: t86 = 9.832, P < 0.0001); however, a few
      students reported some technical difficulties when using computers to view the
      virtual slides. CONCLUSIONS: Although light microscopy is the classical tool of
      teaching histology and pathology, virtual microscopy is a highly preferred
      substitute. We believe that virtual microscopy is a valuable teaching tool that
      enhances student educational experiences.

PMID- 27872548
TI  - Perception of altered smile esthetics among Moroccan professionals and lay
      people.
AB  - OBJECTIVE: To evaluate and compare the impact of altered smile characteristics on
      the perception of smile esthetics between Moroccan dentists and lay people.
      MATERIALS AND METHODS: Thirty-four digital smile photographs displaying
      alterations in crown length and width, lateral incisor gingival margin position,
      gingival exposition, midline diastema, and upper midline deviation were presented
      to a sample of 30 dentists and 30 lay people. The ratings were assessed with a
      visual analog scale. RESULTS: Compared to that of lay people, Moroccan dentists'
      evaluation of the gingival smile was more critical when the decrease in central
      incisor crown length was 2.5 mm (p < 0.001) or greater and when the increase in
      gingival exposition was 4 mm or greater (p < 0.01). Moroccan dentists were also
      critical in their evaluation of maxillary lateral incisor crown width alterations
      (p < 0.05) and incisal midline deviations (p < 0.05). However, the professionals
      and lay people similarly evaluated irregularities in the incisor gingival margin
      position. Increases in the midline diastema were judged critically by both
      Moroccan dentists and lay people. CONCLUSIONS: In this sample, Moroccan dentists
      evaluate smile esthetic alterations more critically than Moroccan lay people.
      This difference in perception of smile discrepancies must be taken into account
      during the finishing phases of orthodontic treatment and restoration of the
      anterior teeth in Moroccan patients.

PMID- 27872549
TI  - Tooth Numbering System in Saudi Arabia: Survey.
AB  - OBJECTIVE: There were four aims of the current study: (1) to find the most
      commonly used Tooth Numbering System (TNS) in Saudi Arabia in both academic and
      non-academic institutions, (2) to identify the most commonly taught TNS in dental
      colleges, (3) to understand the reasons why dental practitioners prefer to use a
      specific TNS, and (4) the consequences of using more than one TNS. MATERIALS AND
      METHOD: Between May 2014 and May 2015, a self-administered questionnaire
      containing 21 questions was randomly distributed to 121 individuals (20 deans of
      dental colleges and 101 heads of governmental dental centers). RESULTS: The most
      commonly used TNS is the Federation Dentaire Internationale (FDI) TNS for both
      primary and permanent dentitions in both academic and non-academic institutions,
      followed by the Palmer TNS and then the Universal TNS. CONCLUSION: The FDI TNS
      proved to be the most taught TNS in dental colleges in Saudi Arabia. It is
      advised that the FDI TNS be implemented as a unified system in Saudi Arabia due
      to the advantages of this particular TNS and the benefits of using one single
      TNS.

PMID- 27872550
TI  - Waterpipe smoking among health sciences university students: Knowledge, attitude
      and patterns of use.
AB  - INTRODUCTION: Although waterpipe smoking is common in Gulf counties, its
      prevalence in Saudi Arabia is uncertain. The purposes of this study were (a) to
      assess the prevalence of waterpipe smoking among healthcare university students
      in Saudi Arabia and (b) to determine their attitudes and practices of waterpipe
      smoking. MATERIALS AND METHODS: A cross-sectional survey was conducted among
      university students of three different health sciences colleges, namely medical,
      dental, and pharmacy, of a public university, through random cluster sampling.
      The questionnaire was designed to ask specific questions related to smoking in
      general and to waterpipe smoking specifically. The study was approved by the
      institutional research & ethics committees. RESULTS: A total of 535 participants
      were included in the study. More than one-third of the participants that reported
      having ever smoked a waterpipe (n = 198, 37%), and the majority of these were
      current smokers (62.1%, n = 123); dental students were the most common (45.5%, n
      = 90). Curiosity and pleasure-seeking were the main factors associated with
      starting waterpipe smoking. About one-sixth (14.9%, n = 80) of the participants
      failed to identify a single harmful effect, while a vast majority of participants
      considered waterpipe smoking to be less unhealthy than cigarette smoking.
      CONCLUSION: Waterpipe smoking is very popular among Saudi university students,
      and knowledge among university students about the dangers of waterpipe smoking is
      alarmingly low.

PMID- 27872551
TI  - Evaluation of fluoride levels in bottled water and their contribution to health
      and teeth problems in the United Arab Emirates.
AB  - Fluoride is needed for better health, yet if ingested at higher levels it may
      lead to health problems. Fluoride can be obtained from different sources, with
      drinking water being a major contributor. In the United Arab Emirates (UAE),
      bottled water is the major source for drinking. The aim of this research is to
      measure fluoride levels in different bottled water brands sold in UAE, to
      determine whether fluoride contributes to better health or health problems. The
      results were compared to international and local standards. Fluoride was present
      in seven out of 23 brands. One brand exhibited high fluoride levels, which
      exceeded all standards, suggesting it may pose health problems. Other brands were
      either below or above standards, suggesting either contribution to better health
      or health problems, depending on ingested amount. A risk assessment suggested a
      potential for non-cancer effects from some brands. The results were compared to
      fluoride levels in bottled water sold in UAE and neighboring countries (e.g.
      Saudi Arabia, Qatar, Kuwait, and Bahrain), over 24 years, to reflect on changes
      in fluoride levels in bottled water in this region. The research presents the
      need for creating, stricter regulations that require careful fluoride monitoring
      and new regulations that require listing fluoride level on the bottled water
      label, internationally and regionally. The research will have local and global
      health impact, as bottled water sold in UAE and neighboring countries, is
      produced locally and imported from international countries, e.g. Switzerland, the
      USA, France, Italy, New Zealand, and Fiji.

PMID- 27872552
TI  - Preserving esthetics, occlusion and occlusal vertical dimension in a patient with
      fixed prostheses seeking dental implant treatment.
AB  - The preservation of esthetics and occlusal vertical dimension is critical in
      patients with existing full-arch tooth-retained fixed prostheses. This clinical
      report describes the provision of a maxillary immediate complete denture in a
      patient with a maxillary full-arch fixed dental prosthesis over nonviable teeth.
      The existing fixed dental prosthesis was used in the fabrication of the maxillary
      immediate complete denture to preserve esthetics. The technique involved
      recording and preservation of the occlusal vertical dimension and occlusion of
      the existing prosthesis. The technique is simple, quick, cost-effective and less
      challenging clinically and technically.

PMID- 27872554
TI  - Planning for Bike Share Connectivity to Rail Transit.
AB  - Bike sharing can play a role in providing access to transit stations and then to
      final destinations, but early implementation of these systems in North America
      has been opportunistic rather than strategic. This study evaluates local
      intermodal plan goals using trip data and associated infrastructure such as
      transit stops and bike share station locations in Austin, Texas, and Chicago,
      Illinois. Bike sharing use data from both cities suggest a weak relationship with
      existing rail stations that could be strengthened through collaborative,
      intermodal planning. The study suggests a planning framework and example language
      that could be tailored to help address the linkage between bike sharing and
      transit. Rather than an exhaustive study of the practice, this study provides
      evidence from these two cities that identify opportunities to improve intermodal
      planning. Cities that are planning or expanding a bike sharing system should
      consider carefully how to leverage this mode with existing modes of transport.
      Regardless of a city's status in implementing a bike sharing system, planners can
      leverage information on existing transport systems for planning at regional and
      local levels.

PMID- 27872553
TI  - Development of a Novel Test for Simultaneous Bacterial Identification and
      Antibiotic Susceptibility.
AB  - Background. Elucidation of a pathogen's antimicrobial susceptibility requires
      subculture after the organism is first isolated. This takes several days,
      requiring patients to be treated with broad-spectrum antibiotics. This approach
      contributes to the development of bacterial resistance. Methods. Microtiter wells
      were coated with a polyclonal antibody targeting the pathogen of interest.
      Bacterial suspensions were added in the presence/absence of selected antibiotics.
      After washing, captured bacteria were detected. Findings. Group B streptococcus
      (GBS), Enterococcus faecalis, and Neisseria gonorrhoeae were each detected at 105
      bacteria/mL following a 20-minute incubation period. Susceptibility to select
      antibiotics was discernable following a 6-hour incubation period (GBS and
      Enterococcus). Sensitivity was increased to 10-2 bacteria/mL for GBS, 10-1
      bacteria/mL for E. faecalis, and 101 bacteria/mL for N. gonorrhoeae following 18
      24-hour culture. Conclusion. This novel assay allows for the highly sensitive and
      specific identification of a pathogen and simultaneous determination of its
      antimicrobial susceptibility in a reduced time.

PMID- 27872555
TI  - Effect of Intravenous High Dose Vitamin C on Postoperative Pain and Morphine Use
      after Laparoscopic Colectomy: A Randomized Controlled Trial.
AB  - Background and Objective. Vitamin C has antioxidant, neuroprotective, and
      neuromodulating effects. Recently, it showed antinociceptive effect as a result
      of the antioxidant properties. Therefore, we designed this study to assess the
      effect of intravenous vitamin C on opiate consumption and pain in patients
      undergoing laparoscopic colectomy. Methods. A total of 100 patients were enrolled
      and allocated to receive 50 mg/kg vitamin C or placebo by intravenous infusion
      immediately after induction of anesthesia. Morphine consumption and scores of
      pain were assessed at 2, 6, and 24 h after completion of surgery. Results. There
      were 97 patients included in the analysis. Patients who received vitamin C had
      higher plasma concentrations of vitamin C at the end of surgery, significantly
      lower morphine consumption at the 2 h after end of surgery, and significantly
      lower pain scores at rest during first 24 h postoperatively. There was no
      significant difference between groups in side effects, fatigue score, or pain
      score during cough. Conclusion. This study shows high dose vitamin C infusion
      decreased postoperative pain during the first 24 h and reduced morphine
      consumption in the early postoperative period. Additional research needed to
      examine whether higher doses of vitamin C and longer infusion times can amplify
      these effects.

PMID- 27872556
TI  - Strongylodon juangonzalezii, a remarkable new species of Strongylodon (Fabaceae)
      from Mulanay, Quezon Province, Philippines.
AB  - A new species, Strongylodon juangonzalezii Hadsall, Alejado & Cajano, collected
      from Buenavista Protected Landscape, Mulanay, Quezon, is hereby described. The
      new species is remarkable for its plagiotropic dense inflorescence made up of 27
      31 flowers per cluster in a lateral branch. Flowers are lilac when young, then
      gradually turn blue when mature. A comparison of the morphology of Strongylodon
      juangonzalezii and related species of Strongylodon in the Philippines is
      provided. Detailed illustration based on the holotype and photos from its natural
      habitat are also included. With this new species, the Philippines now harbors
      eight endemic species of Strongylodon. A key to distinguish the species is
      provided.

PMID- 27872557
TI  - Checklist for the crop weeds of Paraguay.
AB  - Paraguay, a country whose economy is based mainly on agriculture and livestock
      for export, has experienced a major expansion in mechanized crops during the last
      few decades. Despite being heavily dependent on agriculture, Paraguay has very
      limited research on crop weeds, in spite of these having a high economic impact
      on production. This work aims to update and enhance the knowledgebase on the most
      common weeds affecting productive fields throughout the different ecoregions of
      Paraguay. We present here the first checklist of crop weeds for the country,
      which includes a total of 256 taxa (189 species, 10 subspecies, 54 varieties and
      3 forms), with the most species-rich families being Poaceae and Asteraceae
      followed by Malvaceae, Amaranthaceae, Fabaceae and Solanaceae. The list includes
      three new records for the country. Synonyms, distribution details within
      Paraguay, habit and a voucher specimen are provided for each taxon.

PMID- 27872558
TI  - Taxonomic revision and distribution of herbaceous Paramollugo (Molluginaceae) in
      the Eastern Hemisphere.
AB  - The genus Paramollugo with the type species Paramollugo nudicaulis (=Mollugo
      nudicaulis) has recently been described after molecular investigations. Here we
      report two new endemic Malagasy species: Paramollugo simulans and Paramollugo
      elliotii, and transfer a forgotten New Caledonian endemic Mollugo digyna to
      Paramollugo (Paramollugo digyna). Consequently, the number of Paramollugo species
      in the Eastern Hemisphere is increased from three to six. Almost all genus
      representatives (except Paramollugo nudicaulis, which has a wide distribution in
      Southern Asia, Arabia and tropical Africa) are endemic to Madagascar, Somalia, or
      New Caledonia. Since the type of seed coat ornamentation is crucial for species
      delimitation, a diagnostic key with new taxonomically significant carpological
      characters and other new traits is provided for all the herbaceous Paramollugo.
      The distribution patterns of Paramollugo nudicaulis s.str., Paramollugo simulans
      and Paramollugo elliotii are presented.

PMID- 27872559
TI  - A new Globba with large white floral bracts from Peninsular Malaysia.
AB  - Globba magnibracteata Y.Y.Sam, sp. nov. is described and illustrated. Colour
      plates, a preliminary conservation assessment and a discussion of its closely
      related taxa are provided.

PMID- 27872560
TI  - Lecanorchis tabugawaensis (Orchidaceae, Vanilloideae), a new mycoheterotrophic
      plant from Yakushima Island, Japan.
AB  - A new species, Lecanorchis tabugawaensis Suetsugu & Fukunaga, sp. nov. from
      Yakushima Island, Kagoshima Prefecture, Japan, is described and illustrated.
      Lecanorchis tabugawaensis is similar to Lecanorchis taiwaniana, but it is easily
      distinguished by the straight column, the glabrous status of the base of the
      column, the almost entire and narrow labellum morphology, the shorter part of the
      column fused with the labellum and the glabrous status of the apical part of the
      adaxial labellum surface. The new species appears to be restricted to two
      locations, each consisting of only dozens of mature individuals, and is assessed
      as Critically Endangered [CR D1] according to IUCN Red List Categories and
      Criteria.

PMID- 27872561
TI  - Antioxidant effects of captopril against lead acetate-induced hepatic and splenic
      tissue toxicity in Swiss albino mice.
AB  - Considering that lead caused a lot of health problems in the world, the present
      study was carried out to investigate the protective effect of captopril as
      antioxidants to reduce liver and spleen toxicity induced by lead. Animals were
      divided into 3 groups, the 1st group served as control group, the 2nd group
      received 20 mg/kg of lead acetate and the 3rd group received 50 mg/kg of
      captopril one hour prior to lead administration for 5 days. Results showed that
      lead intake caused severe alterations in the liver and spleen manifested by
      hepatocytes degeneration, leukocytic infiltration, fibrosis in liver and moderate
      to severe liver pathological score. Spleen showed ill-defined architecture,
      presence of large macrophages and lymphoid necrosis. Administration of captopril
      reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring
      system. Moreover, reduced toxicity in spleen is represented by reduction in
      necrotic areas, more or less healthy lymphoid follicles and decreasing in
      pathological scoring system.

PMID- 27872562
TI  - Development of quality standards of medicinal mistletoe - Helicanthes elastica
      (Desr.) Danser employing Pharmacopoeial procedures.
AB  - Helicanthes elastica (Desr.) Danser (Loranthaceae), commonly known as Indian
      mango mistletoe, is a parasitic shrub found widely growing on mango trees in
      southern India. Development of monographic quality standards is need of the hour
      for Pharmacopoeial/extra-Pharmacopoeial and folk medicinal plants. Systematic
      pharmacognostical evaluation of leaves of H. elastica has been carried out
      employing Pharmacopoeial procedures of testing herbal drugs. Macro-microscopic
      features of H. elastica leaf were recorded. Ethanolic extract was tested positive
      for alkaloids, steroids, carbohydrates, tannins, saponins and phenols. HPTLC
      fingerprint profile was developed for the identification of extracts using
      reference standard beta-sitosterol glucoside. Results of the present
      investigation would serve as a source of pharmacognostical information and a
      document to control the quality of H. elastica (Desr.) Danser.

PMID- 27872563
TI  - Main vegetation types and plant species diversity along an altitudinal gradient
      of Al Baha region, Saudi Arabia.
AB  - Plant species composition patterns and vegetation types were investigated along
      Elevational Gradients in Al Baha region, Saudi Arabia. Sandy plain, wadis,
      drainage lines, rocky outcrops, hills and fallow lands occur over a wide
      geographic range encompassing variation in plant species and communities among
      these different ecological sites. To provide a quantitatively based
      classification of the vegetation we used Multi Variant Statistical Package (MVSP)
      software, followed by the re-arrangement of a matrix of the similar plant species
      in rows and similar sample sites in columns. Plant density and environmental
      variables were measured and recorded in each quadrat. Two-way indicator species
      analysis and Canonical Correspondence Analysis (CCA) were used to analyze the
      relationships between vegetation and environmental variables, while Arc Map was
      used to analyze the pattern of plant species density. A total of 59 sample plots
      (25 * 25 m), stratified, randomly-placed releves were collected in Al Baha
      region, along a cross section running from south-west to north-west. About 190
      plant species belonging to 59 families were recognized. This study showed that
      these plant species formed 15 vegetation types that primarily correspond mainly
      to different combinations of elevation, and topography. The study concluded that
      this research has provided the first quantitative and systematic survey of the
      vegetation in Al Baha region.

PMID- 27872564
TI  - Effect of 28-homobrassinolide on the performance of sensitive and resistant
      varieties of Vigna radiata.
AB  - A study was undertaken to examine the morpho-physiological alterations under
      different concentrations of 28-homobrassinolide (HBL) in two contrasting
      varieties of Vigna radiata. Sterilized seeds of V. radiata (T-44 and PDM-139)
      were inoculated with specific Rhizobium and allowed to grow and then 14 day old
      seedlings were exposed to different concentrations (0, 10-10, 10-8, or 10-6 M) of
      HBL and allowed to grow under natural environmental conditions. At the 15 and 21
      day stage, plants were harvested to evaluate various parameters. Results clearly
      indicated that growth bio-markers, accumulation of proline and activities of
      various antioxidant enzymes increased significantly in T-44 at a later stage of
      growth in the presence of HBL whereas, 10-8 M showed the most promising response.
      It is concluded that HBL modifies the physiological functions and biochemical
      metabolism of V. radiata by increasing photosynthetic efficiency at an early
      stage of growth and antioxidant system in T-44 at a later stage of plant growth
      that are manifested in growth at later stages. It is believed that increased
      accumulation of proline and enhanced antioxidant system provide strength to the
      plants to withstand environmental cues.

PMID- 27872565
TI  - Evaluation of radical scavenging system in two microalgae in response to
      interactive stresses of UV-B radiation and nitrogen starvation.
AB  - The effects of UV-B radiation and/or deprivation of nitrogen stresses on growth
      rate, some antioxidant compounds, and activities of some antioxidant enzymes,
      superoxide dismutase (SOD; EC1.15.1.1), ascorbate peroxidase (APx; EC1.11.1.11),
      guaiacol peroxidase (GUPx; EC1.11.1.7) and glutathione reductase (GR, EC
      1.6.4.2), as well as the levels of total glutathione pool, UV-B absorbing
      pigments, malondialdehyde (MDA) and H2O2 concentrations were studied in Spirulina
      platensis and Dunaliella salina. Less damage was observed in response to the
      combined UV-B and nitrogen deprivation as shown by growth rate and photosynthetic
      pigments especially in Dunaliella salina. A significant increase in flavonoids
      and phenolics under dual stress was observed. Conversely, a great reduction in
      malondialdehyde (MDA) and H2O2 concentrations were recorded under the combined
      stress compared to the effect of each stress. Furthermore, a significant increase
      in GSH/GSSG ratio toward the control was recorded in response to combined
      stresses, whereas a significant reduction in this ratio was observed in both
      microalgae in response to each stress. Increased activities of antioxidant
      enzymes were recorded under UV-B and nitrogen deprivation stresses.

PMID- 27872566
TI  - Phenotypic and genotypic analysis of pathogenic Escherichia coli virulence genes
      recovered from Riyadh, Saudi Arabia.
AB  - The current study was carried out to evaluate the phenotypic and genotypic
      characterization of avian pathogenic Escherichia coli recovered from Riyadh,
      Saudi Arabia. During the period of 10th February-30th May 2015, 70 E. coli
      strains were isolated from chicken farms located in Riyadh, Saudi Arabia. All
      strains were tested phenotypically by standard microbiological techniques,
      serotyped and the virulence genes of such strains were detected by polymerase
      chain reaction (PCR). Most of the recovered strains from chickens belonged to
      serotype O111:K58 25 strains (35.7%), followed by serotype O157:H7 13 strains
      (18.57%), followed by serotype O114:K90 10 strains (14.29%), then serotype
      O126:K71 9 strains (12.9%), serotype O78:K80 8 strains (11.43%) and in lower
      percentage serotype O114:K90 and O119:K69 5 strains (7.14%). The virulence
      genotyping of E. coli isolates recovered from broilers revealed the presence of
      the uidA gene in all the field isolates (6 serovars) examined in an incidence of
      100%, as well as the cvaC gene was also present in all field isolates (6
      serovars), while the iutA gene and the iss gene were detected in 5 out of 6 field
      serovars in an incidence of 81.43% and 64.29%, respectively. Phenotypical
      examination of the other virulence factors revealed that 65 isolates were
      hemolytic (92.9%), as well as 15 isolates (21.42%) were positive for enterotoxin
      production. Meanwhile, 21 isolates (30%) were positive for verotoxin production,
      58 isolates (82.86%) for the invasiveness and 31 isolates (44.29%) for Congo red
      binding activities of the examined serotypes.

PMID- 27872567
TI  - Vaccination against Corynebacterium pseudotuberculosis infections controlling
      caseous lymphadenitis (CLA) and oedematousskin disease.
AB  - Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a causative
      organism of caseous lymphadenitis (CLA) in sheep and acute disease in buffaloes
      known as oedematous skin disease (OSD). Human affected with the disease show
      liver abscess and abscess in the internal lymph nodes. The vaccination against
      CLA up till now occurs by using formalin inactivated whole cells of biovar 1
      (sheep strain). Combined vaccine composed of formalin inactivated whole cells of
      sheep strain and recombinant phospholipase D (rPLD) and another vaccine composed
      of formalin inactivated whole cells (buffalo origin) and rPLD were prepared in
      Biotechnology center for services and Researches laboratory at Cairo university
      and applied for protection against CLA. Both vaccines induced complete protection
      (100%) against challenge with virulent biovar 1 or biovar 2. Also vaccination
      against OSD was performed by two types of vaccines. Vaccine-1 was composed of
      formalin inactivated whole cell biovar 1 combined with rPLD and the second
      vaccine was composed of formalin inactivated whole cells of biovar 2 combined
      with rPLD. No lesions developed in vaccinated and non vaccinated buffaloes
      challenged with C. pseudotuberculosis biovar revealing that biovar 1 C.
      pseudotuberculosis is not infective for buffaloes. Buffaloes vaccinated with the
      second vaccine and control non vaccinated animals challenged with biovar 2
      (buffalo origin) resulted in development of OSD in all animals. This indicates
      that OSD results due to production of toxin (s) other than PLD. Discovering this
      toxin (s) is of value in formulation of a future vaccine against OSD.

PMID- 27872568
TI  - Weekly iron folic acid supplementation plays differential role in maintaining
      iron markers level in non-anaemic and anaemic primigravida: A randomized
      controlled study.
AB  - : Anaemia during pregnancy is most commonly observed and highly prevalent in
      South-East Asia. Various effective programmes have been laid down for its
      management, mainly daily supplementation of iron folic acid (IFA) tablets.
      Following the same, standard obstetrical practice has included the IFA
      supplementation without requiring the determination of iron deficiency. In this
      study, a total of 120 primigravida (N = 60; non-anaemic (Hb > 11 g/dl) and N = 60
      anaemic (Hb = 8-11 g/dl)) were selected among those attending the Antenatal
      Clinic in Department of Obstetrics and Gynaecology, All India Institute of
      Medical Sciences, Ansari Nagar, New Delhi, India. They were supplemented with
      daily and weekly IFA tablets till 6 weeks postpartum. Corresponding changes in
      haemoglobin level on advance of pregnancy, side effects and compliance associated
      with daily and weekly IFA supplementation and its associations with iron status
      markers were studied. The inflammatory markers were also estimated. The
      statistical significance level (p < 0.05) between the groups were assessed by
      applying unpaired t-test using SPSS (version 16.0). The obtained results
      publicized the salutary role of daily IFA supplementation in improving the
      haemoglobin level and iron status markers in anaemic pregnant women though the
      levels could not reach up to the non-anaemic haemoglobin levels. However, weekly
      IFA supplementation seems to be a better approach in non-anaemic pregnant women
      where almost comparable results were obtained in terms of haematological
      parameters, gestation length and birth weight. CONCLUSION: Weekly IFA
      supplementation found to be as effective as daily supplementation in iron
      sufficient non-anaemic pregnant women whereas anaemic pregnant women should be
      prescribed daily IFA supplementation irrespective of iron replete/deplete state.

PMID- 27872569
TI  - New antimicrobial anthraquinone 6,61-bis (1,5,7-trihydroxy-3
      hydroxymethylanthraquinone) isolated from Streptomyces sp. isolate ERI-26.
AB  - The present report is about Streptomyces sp. isolate ERI-26 isolated from the
      soil sample of Nilgiri forest, Western Ghats. The methanol extract of ERI-26
      showed good antimicrobial activity against tested microbes. The antimicrobial
      novel anthraquinones were purified by bioactivity-guided fractionation using a
      silica gel column and preparative HPLC. The compound was characterized and
      identified by UV, IR, NMR and MASS spectral data. The compound named as 6,61-bis
      (1,5,7-trihydroxy-3-hydroxymethylanthraquinone), showed significant antimicrobial
      activities against tested microbes. The isolated compound inhibited the tested
      bacterial growth, Staphylococcus aureus at 62.5 MUg/ml, Staphylococcus
      epidermidis at 15.62 MUg/m, Bacillus subtilis at 62.5 MUg/ml, fungi; Trichophyton
      mentagrophytes at 15.62 MUg/m Trichophyton simii at 15.62 MUg/ml, Aspergillus
      niger at. 7.81 MUg/ml, Aspergiller flavus at 3.90 MUg/ml, Trichophyton rubrum 296
      at 62.5 MUg/ml, T. rubrum 57/01 at 7.81 MUg/ml, Magnaporthe grisea at 15.62
      MUg/ml. and Botrytis cinerea at 3.90 MUg/ml. Isolated anthraquinone compound and
      its antimicrobial activity were newly reported.

PMID- 27872570
TI  - Influence of premolar extraction or non-extraction orthodontic therapy on the
      angular changes of mandibular third molars.
AB  - AIM: To compare the angular changes of the third molars relative to the occlusal
      plane and to the second molar long axis in extraction group and compare these
      changes with a non extraction group. MATERIALS AND METHODS: The study included
      pre and post treatment panoramic radiograph records of 90 subjects treated by
      first premolar extractions and 90 subjects who had been treated with non
      extraction orthodontic therapy (n = 90). Two angular variables were measured.
      Firstly, the angle between the long axis of the third molar and the occlusal
      plane (M3-OP) and secondly, the angle between the long axis of the third molar
      and the long axis of the second molar (M3-M2). Data were analyzed by paired and
      student's t-test. RESULT: The analyzed data to assess the changes in the third
      molar angulation from pretreatment to post treatment did not vary significantly
      in both the groups (p < 0.05). Both the groups showed decreased angular values.
      The M3-OP angular difference was (-7.3 +/- 2.45) in extraction group as compared
      to (-5.85 +/- 1.77) in non extraction group. The M3-M2 angular difference of (
      4.26 +/- 3.11) in extraction group and (-2.98 +/- 1.74) in non-extraction group
      was observed. CONCLUSION: Extraction of premolars did not demonstrate
      considerable changes on the angulation of the third molars. The factors other
      than premolar extractions may influence the angulation of the third molars.

PMID- 27872571
TI  - Weed species composition and distribution pattern in the maize crop under the
      influence of edaphic factors and farming practices: A case study from Mardan,
      Pakistan.
AB  - Weeds are unwanted plant species growing in ordinary environment. In nature there
      are a total of 8000 weed species out of which 250 are important for agriculture
      world. The present study was carried out on weed species composition and
      distribution pattern with special reference to edaphic factor and farming
      practices in maize crop of District Mardan during the months of August and
      September, 2014. Quadrates methods were used to assess weed species distribution
      in relation to edaphic factor and farming practices. Phytosociological attributes
      such as frequency, relative frequency, density, relative density and Importance
      Values were measured by placing 9 quadrates (1 * 1 m2) randomly in each field.
      Initial results showed that the study area has 29 diverse weed species belonging
      to 27 genera and 15 families distributed in 585 quadrats. Presence and absence
      data sheet of 29 weed species and 65 fields were analyzed through PC-ORD version
      5. Cluster and Two Way Cluster Analyses initiated four different weed communities
      with significant indicator species and with respect to underlying environmental
      variables using data attribute plots. Canonical Correspondence Analyses (CCA) of
      CANOCO software version 4.5 was used to assess the environmental gradients of
      weed species. It is concluded that among all the edaphic factors the strongest
      variables were higher concentration of potassium, organic matter and sandy nature
      of soil. CCA plots of both weed species and sampled fields based on questionnaire
      data concluded the farming practices such as application of fertilizers,
      irrigation and chemical spray were the main factors in determination of weed
      communities.

PMID- 27872572
TI  - Evaluation of the diuretic and urinary electrolyte effects of methanolic extract
      of Peganum harmala L. in Wistar albino rats.
AB  - The use of traditional medicines as a diuretic agent has been increasing in
      recent years. The diuretic activity of a number of plant extracts used as
      diuretic agents in ethnomedicine has been confirmed in experimental animals.
      However, despite the widespread use of Peganum harmala in traditional medicine,
      there is a paucity of data supporting its use as a diuretic agent. Therefore, the
      present study aimed to envisage the true effect and magnitude of diuresis of
      methanolic extract of P. harmala (MEPH) in comparison with a well-known diuretic
      drug furosemide using Wistar albino rats. MEPH was administered orally in three
      different doses (150, 300 and 450 mg/kg) to experimentally dehydrated rats.
      Furosemide (10 mg/kg orally) was used as a reference drug. The diuretic effect of
      the MEPH was evaluated by measuring urine volume, urine pH, urinary electrolyte
      levels, natriuretic and saliuretic effects. The urine volume (in mL) measured at
      5 h and 24 h and electrolyte excretion (Na+, K+, and Cl-) at 24 h duration were
      measured. The urine output and urinary electrolyte excretion were found to be
      significantly higher in rats treated with MEPH as compared to normal rats in a
      dose dependent manner (P < 0.05). The results of our study were comparable to
      furosemide drug. Based on observed results, we can recommend that P. harmala may
      be an effective diuretic, however, toxicity studies should be conducted before
      administration.

PMID- 27872573
TI  - Toxicity of silver nanoparticles on the brain of Oreochromis niloticus and
      Tilapia zillii.
AB  - BACKGROUND: Silver nanoparticles (Ag-NPs) are widely used nowadays in a variety
      of commercial applications including medical, health care, textiles and household
      supplies. OBJECTIVES: The current study was designed to determine the median
      lethal dose (LC50) of Ag-NPs on Oreochromis niloticus and Tilapia zillii.
      METHODS: Acute and sub-acute toxicity study of the Ag-NPs on brain tissues was
      carried out using different concentrations of the NPs at 2 mg L and 4 mg L. These
      concentrations were dispersed in deionized water with the exception of the
      control groups in the experiments. Biochemical and molecular analysis were
      conducted on tissue homogenates in order to evaluate the potential effects of NPs
      on the antioxidant system. RESULTS: The Ag-NP acute toxicity (96 h LC50) values
      of 19.5 +/- 2 and 20 +/- 2.4 mg/L were reported for O. niloticus and T. zillii
      respectively. Fish exposed to 2 mg/L Ag-NPs did not show any significant change
      in the levels of reduced glutathione (GSH), total glutathione (tGSH) levels,
      superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR),
      glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activity or
      genes expression and malondialdehyde (MDA) level. In contrary, a dose of 4 mg/L
      showed a significant reduction in the levels all the above-mentioned parameters
      except in MDA level where it was significantly induced. CONCLUSION: Results
      indicate that exposure of O. niloticus and T. zillii to Ag-NPs (4 mg/L) has
      deleterious effects on brain antioxidant system, whereas a dose of 2 mg/L has no
      effects.

PMID- 27872574
TI  - Prevalence and pattern of dyslipidemia in hyperglycemic patients and its
      associated factors among Pakistani population.
AB  - In diabetes mellitus dyslipidemia is one of the major risk factors for
      cardiovascular disease. In type 2 diabetes mellitus early detection and treatment
      of dyslipidemia can avoid risk for cardiovascular disorder. The present study was
      carried to determine the prevalence and pattern of hyperlipidemia in patients
      with hyperglycemia. The cross sectional study was done in different laboratories
      of Pakistan, the laboratories served patients referred from different government
      and private hospitals between July 2014 and June 2015. All known cases of
      diabetes mellitus were evaluated for their lipid profile. Totally 200 diabetic
      patients were included in the study in which 120 (60%) were males and 80 (40%)
      were females. Prevalence of dyslipidemia among diabetic males was 97.18% while
      for females 87.15%. Among dyslipidemic male the proportion with mixed
      dyslipidemic patients was 17.5%, combined two parameters dyslipidemia was 47.5%
      and isolated single parameter dyslipidemia was 35%. In females these proportions
      in mixed, combined two parameters and isolated single parameter were 16.25%,
      51.25% and 32.5%, respectively. Majority of hyperglycemic patients were
      dyslipidemic. The most prevalent pattern among male was combined dyslipidemia
      with high triglycerides (TG) and low High Density Lipoprotein (HDL) and in female
      it was high Low Density Lipoprotein (LDL) and low HDL. The most prevalent lipid
      abnormality in our study was low HDL followed by high TG.

PMID- 27872575
TI  - The significance and occurrence of TNF receptor polymorphisms in the Saudi
      population.
AB  - Background and objective: On the basis that the inflammatory effects of TNF
      (tumour necrosis factor) are predominantly mediated through interaction with the
      TNF receptor-1 (TNFRSF1A), the current study was designed to establish the
      prevalence of the mutations, R92Q and P46L TNFRSF1A polymorphisms both in the
      general healthy Saudi population, and in Saudi patients carrying inflammatory
      diseases such as atherosclerosis or rheumatoid arthritis. We felt it important to
      report the frequency of the mutations, R92Q and P46L TNFRSF1A polymorphisms in
      healthy Saudi individuals, and those with inflammatory conditions, as well as to
      describe the pattern of immunological factors in individuals expressing R92Q or
      P46L TNFRSF1A. Patients and methods: We collected in PAX gene blood RNA tubes
      (for RT-PCR and sequencing) 500 blood samples from normal healthy individuals
      from the West and Center of Saudi Arabia, as well as 100 from patients with
      atherosclerosis, and 100 patients diagnosed with rheumatoid arthritis. All were
      screened for the levels of soluble TNF, C-reactive protein (CRP), interleukin6
      (IL-6) and sTNFR1. In addition, they were screened for R92Q and P46L TNFRSF1A by
      RT-PCR. Moreover, phenotype and expression of peripheral blood mononuclear cells
      (PBMCs) was performed by flow cytometry (FACS). Results: Across 500 normal
      individuals, 8 (1.6%) expressed both R92Q and P46L mutations. By contrast, of the
      100 patients in our study with atherosclerosis, 34% expressed both the R92Q and
      P46L mutations, whilst 42% of patients with rheumatoid arthritis expressed both
      mutations R92Q and P46L. No significant differences were observed between cell
      markers of normal individuals (CD3, 4, 8, 16, 56, 19, 25, ICAM-1, VLA-4 & l
      selectin) and patients with atherosclerosis. There were significantly high values
      of cell markers in patients with rheumatoid arthritis compared with normal
      individuals both in terms of percentage and absolute counts (p < 0.05). Soluble
      IL-6 and sTNFR1 showed significant decreases in atherosclerosis and rheumatoid
      arthritis when compared with controls (p < 0.05). In addition, CRP and sTNF
      showed significant increases in the atherosclerosis and rheumatoid arthritis
      groups when compared to controls (p < 0.05). Conclusion: Our findings reasonably
      anticipate the presence of TRAPS disease (low penetrance mutations) amongst the
      Saudi population although further studies are needed to confirm these results.

PMID- 27872576
TI  - The alteration of mRNA expression of SOD and GPX genes, and proteins in tomato
      (Lycopersicon esculentum Mill) under stress of NaCl and/or ZnO nanoparticles.
AB  - Five cultivars of tomato having different levels of salt stress tolerance were
      exposed to different treatments of NaCl (0, 3 and 6 g L-1) and ZnO-NPs (0, 15 and
      30 mg L-1). Treatments with NaCl at both 3 and 6 g L-1 suppressed the mRNA levels
      of superoxide dismutase (SOD) and glutathione peroxidase (GPX) genes in all
      cultivars while plants treated with ZnO-NPs in the presence of NaCl, showed
      increments in the mRNA expression levels. This indicated that ZnO-NPs had a
      positive response on plant metabolism under salt stress. Superior expression
      levels of mRNA were observed in the salt tolerant cultivars, Sandpoint and Edkawy
      while the lowest level was detected in the salt sensitive cultivar, Anna Aasa.
      SDS-PAGE showed clear differences in patterns of protein expression among the
      cultivars. A negative protein marker for salt sensitivity and ZnO-NPs was
      detected in cv. Anna Aasa at a molecular weight of 19.162 kDa, while the tolerant
      cultivar Edkawy had two positive markers at molecular weights of 74.991 and
      79.735 kDa.

PMID- 27872577
TI  - Sex determination using discriminant function analysis in Indigenous (Kurubas)
      children and adolescents of Coorg, Karnataka, India: A lateral cephalometric
      study.
AB  - Aim: To test the validity of sex discrimination using lateral cephalometric
      radiograph and discriminant function analysis in Indigenous (Kuruba) children and
      adolescents of Coorg, Karnataka, India. Methods and materials: Six hundred and
      sixteen lateral cephalograms of 380 male and 236 females of age ranging from 6.5
      to 18 years of Indigenous population of Coorg, Karnataka, India called Kurubas
      having a normal occlusion were included in the study. Lateral cephalograms were
      obtained in a standard position with teeth in centric occlusion and lips relaxed.
      Each radiograph was traced and cephalometric landmarks were measured using
      digital calliper. Calculations of 24 cephalometric measurements were performed.
      Results: Males exhibited significantly greater mean angular and linear
      cephalometric measurements as compared to females (p < 0.05) (Table 5). Also,
      significant differences (p < 0.05) were observed in all the variables according
      to age (Table 6). Out of 24 variables, only ULTc predicts the gender. The
      reliability of the derived discriminant function was assessed among study
      subjects; 100% of males and females were recognized correctly. Conclusion: The
      final outcome of this study validates the existence of sexual dimorphism in the
      skeleton as early as 6.5 years of age. There is a need for further research to
      determine other landmarks that can help in sex determination and norms for
      Indigenous (Kuruba) population and also other Indigenous population of Coorg,
      Karnataka, India.

PMID- 27872578
TI  - Morphology and morphogenesis of a new oxytrichid ciliate, Notohymena limus n. sp.
      (Ciliophora, Oxytrichidae) from Delhi, India.
AB  - The morphology and morphogenesis of a new oxytrichid ciliate, Notohymena limus n.
      sp. were studied in vivo and after protargol impregnation. The new ciliate was
      isolated from the sewage sludge at Delhi Jal Board Sewage Treatment Plant located
      at Rithala, Delhi, India, using the non-flooded Petri dish method. N. limus n.
      sp. is characterized as follows: flexible dorsoventrally flattened ellipsoidal
      body; Notohymena-pattern undulating membranes; adoral zone of membranelles (AZM)
      occupied about 39% of the body length, and consists of around 26 membranelles;
      large and deep buccal cavity; colorless subpellicular granules present in groups
      and arranged around the bases of dorsal bristles; 4 macronuclear nodules; 2
      micronuclei; 18 fronto-ventral-transverse (FVT) cirri in typical Oxytricha
      pattern; 6 dorsal rows of bristles; 3 caudal cirri; about 16 right and 15 left
      marginal cirri; N. limus n. sp. is a new species on the basis of the combination
      of morphological, morphometric and morphogenetic characteristic features.

PMID- 27872579
TI  - Simultaneous dual targeting of Par-4 and G6PD: a promising new approach in cancer
      therapy? Quintessence of a literature review on survival requirements of tumor
      cells.
AB  - : The aim of this hypothesis is to propose a new approach in targeted therapy of
      cancer: The simultaneous, dual targeting of two single molecules, Par-4 and G6PD,
      rather than inhibition of full-length signaling pathways. RATIONALE: Targeted
      inhibition of especially two survival signaling pathways (PI3K/AKT/mTOR and
      MAPK/ERK) is frequently tried, however, a major breakthrough has not yet been
      reported. Inhibition of complete pathways naturally goes along with a variety of
      dose-limiting side effects thus contributing to poor efficacy of the administered
      drugs. This essay offers a synopsis of relevant studies to support the above
      mentioned idea-targeting of two single molecules which either are crucial for
      tumor growth and cancer-cell-survival: on one side, Par-4-activation selectively
      triggers apoptosis of tumor cells thus reversing their characteristic feature
      immortality. On the other side inhibition of G6PD breaks the energy supply of
      tumor cells, weakens their defence against oxidative stress and thereby enhances
      the sensitivity of tumor cells to oxidative agents (e.g. chemotherapy). Advantage
      of the proposed dual Par-4/G6PD-therapy is good tolerability and-especially when
      administered along with conventional therapy-less frequent emergence of
      resistance.

PMID- 27872580
TI  - Untargeted polar metabolomics of transformed MDA-MB-231 breast cancer cells
      expressing varying levels of human arylamine N-acetyltransferase 1.
AB  - INTRODUCTION: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II
      xenobiotic metabolizing enzyme found in almost all tissues. Expression of NAT1 is
      elevated in several cancers including breast cancer. However, the exact mechanism
      by which NAT1 expression affects cancer risk and progression remains unclear.
      OBJECTIVE: This study explored polar metabolome differences between MDA-MB-231
      breast cancer cells expressing varying levels of NAT1 activity using an
      untargeted approach. METHODS: Three MDA-MB-231 breast adenocarcinoma cell lines
      that stably express wild-type, increased, and decreased levels of human NAT1 were
      investigated for differences in polar metabolic profile using a comprehensive two
      dimensional gas chromatography time-of-flight mass spectrometry (GC*GC-TOF MS)
      system. RESULTS: Increased levels of human NAT1 in the transformed cell lines
      resulted in a statistically significant decreased abundance of the metabolite
      palmitoleic acid (q = 0.0006), when compared to normal and decreased levels of
      human NAT1. The fatty acid synthesis pathway utilizes acetyl coenzyme A (acetyl
      CoA) in the first two reactions of the pathway and eventually leads to the
      synthesis of palmitoleic acid. CONCLUSION: These data suggest a link between
      increased levels of NAT1 activity and decreased flux of acetyl-CoA through this
      portion of the fatty acid synthesis pathway.

PMID- 27872583
TI  - Ablation of Sphingosine 1-Phosphate Receptor Subtype 3 Impairs Hippocampal Neuron
      Excitability In vitro and Spatial Working Memory In vivo.
AB  - Understanding the role of the bioactive lipid mediator sphingosine 1-phosphate
      (S1P) within the central nervous system has recently gained more and more
      attention, as it has been connected to major diseases such as multiple sclerosis
      and Alzheimer's disease. Even though much data about the functions of the five
      S1P receptors has been collected for other organ systems, we still lack a
      complete understanding for their specific roles, in particular within the brain.
      Therefore, it was the aim of this study to further elucidate the role of S1P
      receptor subtype 3 (S1P3) in vivo and in vitro with a special focus on the
      hippocampus. Using an S1P3 knock-out mouse model we applied a range of behavioral
      tests, performed expression studies, and whole cell patch clamp recordings in
      acute hippocampal slices. We were able to show that S1P3 deficient mice display a
      significant spatial working memory deficit within the T-maze test, but not in
      anxiety related tests. Furthermore, S1p3 mRNA was expressed throughout the
      hippocampal formation. Principal neurons in area CA3 lacking S1P3 showed
      significantly increased interspike intervals and a significantly decreased input
      resistance. Upon stimulation with S1P CA3 principal neurons from both wildtype
      and [Formula: see text] mice displayed significantly increased evoked EPSC
      amplitudes and decay times, whereas rise times remained unchanged. These results
      suggest a specific involvement of S1P3 for the establishment of spatial working
      memory and neuronal excitability within the hippocampus.

PMID- 27872584
TI  - Editorial: Anatomy and Plasticity in Large-Scale Brain Models.

PMID- 27872581
TI  - A Trigger for Opioid Misuse: Chronic Pain and Stress Dysregulate the Mesolimbic
      Pathway and Kappa Opioid System.
AB  - Pain and stress are protective mechanisms essential in avoiding harmful or
      threatening stimuli and ensuring survival. Despite these beneficial roles,
      chronic exposure to either pain or stress can lead to maladaptive hormonal and
      neuronal modulations that can result in chronic pain and a wide spectrum of
      stress-related disorders including anxiety and depression. By inducing allostatic
      changes in the mesolimbic dopaminergic pathway, both chronic pain and stress
      disorders affect the rewarding values of both natural reinforcers, such as food
      or social interaction, and drugs of abuse. Despite opioids representing the best
      therapeutic strategy in pain conditions, they are often misused as a result of
      these allostatic changes induced by chronic pain and stress. The kappa opioid
      receptor (KOR) system is critically involved in these neuronal adaptations in
      part through its control of dopamine release in the nucleus accumbens. Therefore,
      it is likely that changes in the kappa opioid system following chronic exposure
      to pain and stress play a key role in increasing the misuse liability observed in
      pain patients treated with opioids. In this review, we will discuss how chronic
      pain and stress-induced pathologies can affect mesolimbic dopaminergic
      transmission, leading to increased abuse liability. We will also assess how the
      kappa opioid system may underlie these pathological changes.

PMID- 27872582
TI  - Separate Ionotropic and Metabotropic Glutamate Receptor Functions in
      Depotentiation vs. LTP: A Distinct Role for Group1 mGluR Subtypes and NMDARs.
AB  - Depotentiation (DP) is a mechanism by which synapses that have recently undergone
      long-term potentiation (LTP) can reverse their synaptic strengthening within a
      short time-window after LTP induction. Group 1 metabotropic glutamate receptors
      (mGluRs) were shown to be involved in different forms of LTP and long-term
      depression (LTD), but little is known about their roles in DP. Here, we generated
      DP by applying low-frequency stimulation (LFS) at 5 Hz after LTP had been induced
      by a single train of theta-burst-stimulation (TBS). While application of LFS for
      2 min (DP2') generated only a short-lasting DP that was independent of the
      activation of N-methyl-D-aspartate receptors (NMDARs) and group 1 mGluRs, LFS
      given for 8 min (DP8') induced a robust DP that was maintained for at least 2 h.
      This strong form of DP was contingent on NMDAR activation. Interestingly, DP8'
      appears to include a metabotropic NMDAR function because it was blocked by the
      competitive NMDAR antagonist D-AP5 but not by the use-dependent inhibitor MK-801
      or high Mg2+. Furthermore, DP8' was enhanced by application of the mGluR1
      antagonist (YM 298198, 1 MUM). The mGluR5 antagonist 2-Methyl-6(phenylethynyl)
      pyridine (MPEP, 40 MUM), in contrast, failed to affect it. The induction of LTP,
      in turn, was NMDAR dependent (as tested with D-AP5), and blocked by MPEP but not
      by YM 298198. These results indicate a functional dissociation of mGluR1 and
      mGluR5 in two related and consecutively induced types of NMDAR-dependent synaptic
      plasticity (LTP -> DP) with far-reaching consequences for their role in
      plasticity and learning under normal and pathological conditions.

PMID- 27872586
TI  - Loss of Ensemble Segregation in Dentate Gyrus, but not in Somatosensory Cortex,
      during Contextual Fear Memory Generalization.
AB  - The details of contextual or episodic memories are lost and generalized with the
      passage of time. Proper generalization may underlie the formation and
      assimilation of semantic memories and enable animals to adapt to ever-changing
      environments, whereas overgeneralization of fear memory evokes maladaptive fear
      responses to harmless stimuli, which is a symptom of anxiety disorders such as
      post-traumatic stress disorder (PTSD). To understand the neural basis of fear
      memory generalization, we investigated the patterns of neuronal ensemble
      reactivation during memory retrieval when contextual fear memory expression is
      generalized using transgenic mice that allowed us to visualize specific neuronal
      ensembles activated during memory encoding and retrieval. We found preferential
      reactivations of neuronal ensembles in the primary somatosensory cortex (SS),
      when mice were returned to the conditioned context to retrieve their memory 1 day
      after conditioning. In the hippocampal dentate gyrus (DG), exclusively separated
      ensemble reactivation was observed when mice were exposed to a novel context.
      These results suggest that the DG as well as the SS were likely to distinguish
      the two different contexts at the ensemble activity level when memory is not
      generalized at the behavioral level. However, 9 days after conditioning when
      animals exhibited generalized fear, the unique reactivation pattern in the DG,
      but not in the SS, was lost. Our results suggest that the alternations in the
      ensemble representation within the DG, or in upstream structures that link the
      sensory cortex to the hippocampus, may underlie generalized contextual fear
      memory expression.

PMID- 27872585
TI  - The Pedunculopontine Tegmental Nucleus as a Motor and Cognitive Interface between
      the Cerebellum and Basal Ganglia.
AB  - As an important component of ascending activating systems, brainstem cholinergic
      neurons in the pedunculopontine tegmental nucleus (PPTg) are involved in the
      regulation of motor control (locomotion, posture and gaze) and cognitive
      processes (attention, learning and memory). The PPTg is highly interconnected
      with several regions of the basal ganglia, and one of its key functions is to
      regulate and relay activity from the basal ganglia. Together, they have been
      implicated in the motor control system (such as voluntary movement initiation or
      inhibition), and modulate aspects of executive function (such as motivation). In
      addition to its intimate connection with the basal ganglia, projections from the
      PPTg to the cerebellum have been recently reported to synaptically activate the
      deep cerebellar nuclei. Classically, the cerebellum and basal ganglia were
      regarded as forming separated anatomical loops that play a distinct functional
      role in motor and cognitive behavioral control. Here, we suggest that the PPTg
      may also act as an interface device between the basal ganglia and cerebellum. As
      such, part of the therapeutic effect of PPTg deep brain stimulation (DBS) to
      relieve gait freezing and postural instability in advanced Parkinson's disease
      (PD) patients might also involve modulation of the cerebellum. We review the
      anatomical position and role of the PPTg in the pathway of basal ganglia and
      cerebellum in relation to motor control, cognitive function and PD.

PMID- 27872587
TI  - The Association between Anomalous Self-experiences, Self-esteem and Depressive
      Symptoms in First Episode Schizophrenia.
AB  - Background: Anomalous self-experiences (ASEs) aggregate in schizophrenia spectrum
      disorders, but the relationship between ASEs, and depression has been studied to
      a limited extent. Lower self-esteem has been shown to be associated with
      depression in early psychosis. Our hypothesis is that ASEs in early phases of
      schizophrenia are linked to lower levels of self-esteem, which in turn is
      associated with depression. Aim: The aim is to examine the relationship between
      ASEs, self-esteem and depression in first-episode schizophrenia spectrum
      disorders. Method: ASEs were assessed in 55 patients with first-episode
      schizophrenia by means of the Examination of anomalous Self-Experience (EASE)
      instrument. Assessment of depression was based on the Calgary Depression Scale
      for Schizophrenia (CDSS). Self-esteem was measured using the Rosenberg Self
      Esteem Scale (RSES). Symptom severity was assessed using the Structured Clinical
      Interview for the Positive and Negative Syndrome Scale (SCI-PANSS). Substance
      misuse was measured with the Drug Use Disorder Identification Test (DUDIT), and
      alcohol use was measured with the Alcohol Use Disorder Identification Test
      (AUDIT). Data on childhood adjustment were collected using the Premorbid
      Adjustment Scale (PAS). Data on childhood trauma were collected using the
      Norwegian version of the Childhood Trauma Questionnaire, short form (CTQ-SF).
      Results: Analyses detected a significant association between current depression
      and ASEs as measured by the EASE in women, but not in men. The effect of ASEs on
      depression appeared to be mediated by self-esteem. No other characteristics
      associated with depression influenced the relationship between depression, self
      esteem and ASEs. Conclusion: Evaluating ASEs can assist clinicians in
      understanding patients' experience of self-esteem and depressive symptoms. The
      complex interaction between ASEs, self-esteem, depression and suicidality could
      be a clinical target for the prevention of suicidality in this patient group.

PMID- 27872589
TI  - Corrigendum: No Effect of Anodal Transcranial Direct Current Stimulation Over the
      Motor Cortex on Response-Related ERPs during a Conflict Task.
AB  - [This corrects the article on p. 384 in vol. 10, PMID: 27547180.].

PMID- 27872588
TI  - Conversation Therapy with People with Aphasia and Conversation Partners using
      Video Feedback: A Group and Case Series Investigation of Changes in Interaction.
AB  - Conversation therapies employing video for feedback and to facilitate outcome
      measurement are increasingly used with people with post-stroke aphasia and their
      conversation partners; however the evidence base for change in everyday
      interaction remains limited. We investigated the effect of Better Conversations
      with Aphasia (BCA), an intervention that is freely available online at
      https://extend.ucl.ac.uk/. Eight people with chronic agrammatic aphasia, and
      their regular conversation partners participated in the tailored 8 week program
      involving significant video feedback. We explored changes in: (i) conversation
      facilitators (such as multi-modal turns by people with aphasia); and (ii)
      conversation barriers (such as use of test questions by conversation partners).
      The outcome of intervention was evaluated directly by measuring change in video
      recorded everyday conversations. The study employed a pre-post design with
      multiple 5 minute samples of conversation before and after intervention, scored
      by trained raters blind to the point of data collection. Group level analysis
      showed no significant increase in conversation facilitators. There was, however,
      a significant reduction in the number of conversation barriers. The case series
      data revealed variability in conversation behaviors across occasions for the same
      dyad and between different dyads. Specifically, post-intervention there was a
      significant increase in facilitator behaviors for two dyads, a decrease for one
      and no significant change for five dyads. There was a significant decrease in
      barrier behaviors for five dyads and no significant change for three dyads. The
      reduction in barrier behaviors was considerable; on average change from over
      eight to fewer than three barrier behaviors in 5 minutes of conversation. The pre
      post design has the limitation of no comparison group. However, change occurs in
      targeted conversational behaviors and in people with chronic aphasia and their
      partners. The findings suggest change can occur after eight therapy sessions and
      have implications for clinical practice. A reduction in barrier behaviors may be
      easier to obtain, although the controlled case series results demonstrate a
      significant increase in conversation facilitators is also possible. The
      rehabilitation tool is available online and video technology was central to
      delivering intervention and evaluating change.

PMID- 27872590
TI  - Test-Retest Reliability of a Serious Game for Delirium Screening in the Emergency
      Department.
AB  - Introduction: Cognitive screening in settings such as emergency departments (ED)
      is frequently carried out using paper-and-pencil tests that require
      administration by trained staff. These assessments often compete with other
      clinical duties and thus may not be routinely administered in these busy
      settings. Literature has shown that the presence of cognitive impairments such as
      dementia and delirium are often missed in older ED patients. Failure to recognize
      delirium can have devastating consequences including increased mortality (Kakuma
      et al., 2003). Given the demands on emergency staff, an automated cognitive test
      to screen for delirium onset could be a valuable tool to support delirium
      prevention and management. In earlier research we examined the concurrent
      validity of a serious game, and carried out an initial assessment of its
      potential as a delirium screening tool (Tong et al., 2016). In this paper, we
      examine the test-retest reliability of the game, as it is an important criterion
      in a cognitive test for detecting risk of delirium onset. Objective: To
      demonstrate the test-retest reliability of the screening tool over time in a
      clinical sample of older emergency patients. A secondary objective is to assess
      whether there are practice effects that might make game performance unstable over
      repeated presentations. Materials and Methods: Adults over the age of 70 were
      recruited from a hospital ED. Each patient played our serious game in an initial
      session soon after they arrived in the ED, and in follow up sessions conducted at
      8-h intervals (for each participant there were up to five follow up sessions,
      depending on how long the person stayed in the ED). Results: A total of 114
      adults (61 females, 53 males) between the ages of 70 and 104 years (M = 81 years,
      SD = 7) participated in our study after screening out delirious patients. We
      observed a test-retest reliability of the serious game (as assessed by
      correlation r-values) between 0.5 and 0.8 across adjacent sessions. Conclusion:
      The game-based assessment for cognitive screening has relatively strong test
      retest reliability and little evidence of practice effects among elderly
      emergency patients, and may be a useful supplement to existing cognitive
      assessment methods.

PMID- 27872592
TI  - A Pyrazolo[3,4-d]pyrimidine Compound Reduces Cell Viability and Induces Apoptosis
      in Different Hematological Malignancies.
AB  - Molecular targeted therapies are based upon drugs acting on tumors by interfering
      with specific targets involved in growth and spread of cancer. Many targeted
      therapies were approved by Food and Drug Administration as standard treatment,
      others were introduced into preclinical or clinical studies on hematological
      malignancies (HMs). The development of drug-resistance in some HMs and the lack
      of effective treatments in other ones emphasized the need for searching new
      molecular targets and therapeutic agents. The aim of this study was to evaluate
      the effects of 4c pyrazolo[3,4-d]pyrimidine compound, a Src inhibitor, on
      lymphoid and myeloid neoplasms. Here, we demonstrated its ability to reduce cell
      viability, induce apoptosis and cell cycle arrest in lymphoid cell lines such as
      Jurkat, SKMM1, Derl-2/7, and myeloid cell lines, such as Jurl-MK1. Moreover, we
      reported a high expression of a Src kinase, Fyn, in these cell lines compared to
      healthy subjects. This study was a starting point to investigate 4c pyrazolo[3,4
      d]pyrimidine compound as a drug for HMs and Src kinases as its potential
      molecular targets.

PMID- 27872593
TI  - Length of Hospital Stay and Bed Occupancy Rates in Former Yugoslav Republics 1989
      2015.

PMID- 27872591
TI  - Mild Cognitive Impairment Is Not "Mild" at All in Altered Activation of Episodic
      Memory Brain Networks: Evidence from ALE Meta-Analysis.
AB  - The present study conducted a quantitative meta-analysis aiming at assessing
      consensus across the functional neuroimaging studies of episodic memory in
      individuals with amnestic mild cognitive impairment (aMCI) and elucidating
      consistent activation patterns. An activation likelihood estimation (ALE) was
      conducted on the functional neuroimaging studies of episodic encoding and
      retrieval in aMCI individuals published up to March 31, 2015. Analyses covered 24
      studies, which yielded 770 distinct foci. Compared to healthy controls, aMCI
      individuals showed statistically significant consistent activation differences in
      a widespread episodic memory network, not only in the bilateral medial temporal
      lobe and prefrontal cortex, but also in the angular gyrus, precunes, posterior
      cingulate cortex, and even certain more basic structures. The present ALE meta
      analysis revealed that the abnormal patterns of widespread episodic memory
      network indicated that individuals with aMCI may not be completely "mild" in
      nature.

PMID- 27872594
TI  - Modafinil Induces Rapid-Onset Behavioral Sensitization and Cross-Sensitization
      with Cocaine in Mice: Implications for the Addictive Potential of Modafinil.
AB  - There is substantial controversy about the addictive potential of modafinil, a
      wake-promoting drug used to treat narcolepsy, proposed as pharmacotherapy for
      cocaine abuse, and used indiscriminately by healthy individuals due to its
      positive effects on arousal and cognition. The rapid-onset type of behavioral
      sensitization (i.e., a type of sensitization that develops within a few hours
      from the drug priming administration) has been emerged as a valuable tool to
      study binge-like patterns of drug abuse and the neuroplastic changes that occur
      quickly after drug administration that ultimately lead to drug abuse. Our aim was
      to investigate the possible development of rapid-onset behavioral sensitization
      to modafinil and bidirectional rapid-onset cross-sensitization with cocaine in
      male Swiss mice. A priming injection of a high dose of modafinil (64 mg/kg)
      induced rapid-onset behavioral sensitization to challenge injections of modafinil
      at the doses of 16, 32, and 64 mg/kg, administered 4 h later. Furthermore, rapid
      onset cross-sensitization was developed between modafinil and cocaine (64 mg/kg
      modafinil and 20 mg/kg cocaine), in a bidirectional way. These results were not
      due to residual levels of modafinil as the behavioral effects of the priming
      injection of modafinil were no longer present and modafinil plasma concentration
      was reduced at 4 h post-administration. Taken together, the present findings
      provide preclinical evidence that modafinil can be reinforcing per se and can
      enhance the reinforcing effects of stimulants like cocaine within hours after
      administration.

PMID- 27872596
TI  - Different Relationship between hsp70 mRNA and hsp70 Levels in the Heat Shock
      Response of Two Salmonids with Dissimilar Temperature Preference.
AB  - The heat shock response (HSR) refers to the rapid production of heat shock
      proteins (hsps) in response to a sudden increase in temperature. Its regulation
      by heat shock factors is a good example of how gene expression is
      transcriptionally regulated by environmental stresses. In contrast, little is
      known about post-transcriptional regulation of the response. The heat shock
      response is often used to characterize the temperature tolerance of species with
      the rationale that whenever the response sets on, a species is approaching its
      lethal temperature. It has commonly been considered that an increase in hsp mRNA
      gives an accurate indication that the same happens to the protein level, but this
      need not be the case. With climate change, understanding the effects of
      temperature on gene expression of especially polar organisms has become
      imperative to evaluate how both biodiversity and commercially important species
      respond, since temperature increases are expected to be largest in polar areas.
      Here we studied the HSR of two phylogenetically related Arctic species, which
      differ in their temperature tolerance with Arctic charr having lower maximally
      tolerated temperature than Atlantic salmon. Arctic charr acclimated to 15 degrees
      C and exposed to 7 degrees C temperature increase for 30 min showed both an
      increase in hsp70 mRNA and hsp70 whereas in salmon only hsp70 mRNA increased. Our
      results indicate that the temperature for transcriptional induction of hsp can be
      different from the one required for a measurable change in inducible hsp level.
      The species with lower temperature tolerance, Arctic charr, are experiencing
      temperature stress already at the higher acclimation temperature, 15 degrees C,
      as their hsp70 mRNA and hsp70 levels were higher, and they grow less than fish at
      8 degrees C (whereas for salmon the opposite is true). Consequently, charr
      experience more drastic heat shock than salmon. Although further studies are
      needed to establish the temperature range and length of exposure where hsp mRNA
      and hsp level are disconnected, the observation suggests that by measuring both
      hsp mRNA and hsp level, one can evaluate if a species is approaching the higher
      end of its temperature tolerance, and thus evaluate the vulnerability of an
      organism to the challenges imposed by elevated water temperature.

PMID- 27872597
TI  - Commentary: The Spinal Cord Has an Intrinsic System for the Control of pH.

PMID- 27872600
TI  - Optimal Experience and Personal Growth: Flow and the Consolidation of Place
      Identity.
AB  - This study examined the relationship between flow experience and place identity,
      based on eudaimonistic identity theory (EIT) which prioritizes self-defining
      activities as important for an individual's identification of his/her goals,
      values, beliefs, and interests corresponding to one's own identity development or
      enhancement. This study focuses on place identity, the identity's features
      relating to a person's relation with her/his place. The study is also based on
      flow theory, according to which some salient features of an activity experience
      are important for happiness and well-being. Questionnaire surveys on Italian and
      Greek residents focused on their perceived flow and place identity in relation to
      their own specific local place experiences. The overall findings revealed that
      flow experience occurring in one's own preferred place is widely reported as
      resulting from a range of self-defining activities, irrespective of gender or
      age, and it is positively and significantly associated with one's own place
      identity. Such findings provide the first quantitative evidence about the link
      between flow experienced during meaningfully located self-defining activities and
      identity experienced at the place level, similarly to the corresponding personal
      and social levels that had been previously already empirically tested. Results
      are also discussed in terms of their implications for EIT's understanding and
      enrichment, especially by its generalization from the traditional, personal
      identity level up to that of place identity. More generally, this study has
      implications for maintaining or enhancing one's own place identity, and therefore
      people-place relations, by means of facilitating a person's flow experience
      within psychologically meaningful places.

PMID- 27872595
TI  - Redox Mechanism of Reactive Oxygen Species in Exercise.
AB  - It is well known that regular exercise can benefit health by enhancing
      antioxidant defenses in the body. However, unaccustomed and/or exhaustive
      exercise can generate excessive reactive oxygen species (ROS), leading to
      oxidative stress-related tissue damages and impaired muscle contractility. ROS
      are produced in both aerobic and anaerobic exercise. Mitochondria, NADPH oxidases
      and xanthine oxidases have all been identified as potential contributors to ROS
      production, yet the exact redox mechanisms underlying exercise-induced oxidative
      stress remain elusive. Interestingly, moderate exposure to ROS is necessary to
      induce body's adaptive responses such as the activation of antioxidant defense
      mechanisms. Dietary antioxidant manipulation can also reduce ROS levels and
      muscle fatigue, as well as enhance exercise recovery. To elucidate the complex
      role of ROS in exercise, this review updates on new findings of ROS origins
      within skeletal muscles associated with various types of exercises such as
      endurance, sprint and mountain climbing. In addition, we will examine the
      corresponding antioxidant defense systems as well as dietary manipulation against
      damages caused by ROS.

PMID- 27872599
TI  - Confirmatory Factor Analysis of the 12-Item Center for Epidemiologic Studies
      Depression Scale among Blacks and Whites.
AB  - BACKGROUND: The Center for Epidemiologic Studies Depression (CES-D) scale is one
      of the most widely used tools to measure depressive symptoms in epidemiological
      studies. Given the importance of cross-racial measurement equivalence of the CES
      D scale for research, we performed confirmatory factor analysis (CFA) of the 12
      item CES-D in a nationally representative sample of Black and White adults in the
      United States. METHODS: We used data from the National Survey of American Life
      (NSAL), 2001-2003. A total number of 3570 Blacks (African-Americans) and 891 non
      Hispanic Whites were included in the present study. CFA was carried out on the 12
      item CES-D scale using multi-group structural equation modeling. RESULTS: For
      both Blacks and Whites, the best fitting model was found to be the 3-factor
      model, indicating invariance of factor structure between Blacks and Whites. A
      statistically different fit of the models with and without constraints indicated
      lack of invariance of factor loadings between Blacks and Whites. Some of the
      positive (i.e., "as good" and "hopeful") and interpersonal (i.e., "people were
      unfriendly") items showed poor loadings, even in the 3-factor solution that
      allowed separate domains for positive affect, negative affect, and interpersonal
      problems. Despite the good fit of our final model, more items (i.e., "as good,"
      "hopeful," "keeping mind," and "everything effort") had poorer loadings in Blacks
      than Whites (i.e., "as good"). CONCLUSION: There is invariance in factor
      structure but lack of invariance in factor/item loadings between Blacks and
      Whites. These findings have implications for cross-racial studies of depressive
      symptoms using CES-D scale among Blacks and Whites. Further research is warranted
      to scrutinize the role of socioeconomics and culture in explaining the lack of
      invariance of the CES-D scale between Blacks and Whites.

PMID- 27872598
TI  - Futsal Match-Related Fatigue Affects Running Performance and Neuromuscular
      Parameters but Not Finishing Kick Speed or Accuracy.
AB  - Purpose: The aim of the present study was to investigate the influence of futsal
      match-related fatigue on running performance, neuromuscular variables, and
      finishing kick speed and accuracy. Methods: Ten professional futsal players
      participated in the study (age: 22.2 +/- 2.5 years) and initially performed an
      incremental protocol to determine maximum oxygen uptake ([Formula: see text]:
      50.6 +/- 4.9 mL.kg-1.min-1). Next, simulated games were performed, in four
      periods of 10 min during which heart rate and blood lactate concentration were
      monitored. The entire games were video recorded for subsequent automatic
      tracking. Before and immediately after the simulated game, neuromuscular function
      was measured by maximal isometric force of knee extension, voluntary activation
      using twitch interpolation technique, and electromyographic activity. Before, at
      half time, and immediately after the simulated game, the athletes also performed
      a set of finishing kicks for ball speed and accuracy measurements. Results: Total
      distance covered (1st half: 1986.6 +/- 74.4 m; 2nd half: 1856.0 +/- 129.7 m, P =
      0.00) and distance covered per minute (1st half: 103.2 +/- 4.4 m.min-1; 2nd half:
      96.4 +/- 7.5 m.min-1, P = 0.00) demonstrated significant declines during the
      simulated game, as well as maximal isometric force of knee extension (Before:
      840.2 +/- 66.2 N; After: 751.6 +/- 114.3 N, P = 0.04) and voluntary activation
      (Before: 85.9 +/- 7.5%; After: 74.1 +/- 12.3%, P = 0.04), however ball speed and
      accuracy during the finishing kicks were not significantly affected. Conclusion:
      Therefore, we conclude that despite the decline in running performance and
      neuromuscular variables presenting an important manifestation of central fatigue,
      this condition apparently does not affect the speed and accuracy of finishing
      kicks.

PMID- 27872601
TI  - The Role of Father Involvement and Marital Satisfaction in the Development of
      Family Interactive Abilities: A Multilevel Approach.
AB  - The study aims to investigate the development of family interactions from
      pregnancy to preschool age in a longitudinal perspective, using multilevel
      analysis. Also, it explored the impact of couple relationship and father
      involvement in childcare on the developmental trend of the quality of mother
      father-child interactions. One hundred and three primiparous families were
      assessed at 7th month of pregnancy, 4th, 9th, and 18th months of child's life and
      during preschool age (36-48th), using the observational procedure named, Lausanne
      Trilogue Play. Parents' perception of marital satisfaction was assessed with the
      Dyadic Adjustment Scale at each point of measure; moreover, in the postnatal
      assessment, parents completed the Father Involvement Questionnaire. Results
      showed that family interactions increase over time. Secondly, a decrease of
      marital adjustment is associated with an improvement of the quality of family
      interactions. Moreover, father involvement predicts the quality of family
      interactions from the earliest stages of child's life. In a longitudinal
      perspective, family interactions and marital quality show opposite developmental
      trends and father's involvement represents a particularly important feature of
      the family.

PMID- 27872603
TI  - Age Differences in Consumer Decision Making under Option Framing: From the
      Motivation Perspective.
AB  - Option framing effect is the phenomena that participants often accept more
      options when they are asked to delete undesired options from a full model
      (subtractive framing) than they do when they are instructed to add desired
      options to a base model (additive framing). Whether the same effect exists in
      different age groups is less well known. To explore the roles of age and purchase
      motivations on the option framing effect for automobiles purchases, this study
      adopted a 3 (age group: younger, middle-aged, vs. older) * 2 (option framing:
      additive vs. subtractive) * 2 (focus condition: information vs. emotion) mixed
      design. To manipulate purchase motivations, participants in the three age groups
      were instructed to focus on the ratio of utility and price of options
      (information-focus) or the extent of pleasure induced by the options (emotion
      focus) when they made purchase decisions in two framing conditions. The results
      revealed similar option framing effect across all age groups in the information
      focus condition regarding the total price paid for accepted options. In contrast,
      the framing effect was not found in the emotion-focus condition. In addition,
      older adults accepted more options and an overall higher price than younger and
      middle-aged adults in both focus conditions. This difference was more obvious in
      the emotion-focus condition than in the information-focus condition. Moreover,
      both the number of accepted options and the total accepted price of the younger
      group in the information-focus condition were higher than those in the emotion
      focus condition, whereas the older and middle-aged groups accepted same number of
      options and price between two focus conditions. These results imply that purchase
      motivation is a moderator of the option framing effect and age characteristics
      linked with motivations must be considered in sales.

PMID- 27872604
TI  - Editorial: Cognitive Event-Related Potentials in Psychopathology: New
      Experimental and Clinical Perspectives.

PMID- 27872602
TI  - Perceptual Averaging in Individuals with Autism Spectrum Disorder.
AB  - There is mounting evidence that observers rely on statistical summaries of visual
      information to maintain stable and coherent perception. Sensitivity to the mean
      (or other prototypical value) of a visual feature (e.g., mean size) appears to be
      a pervasive process in human visual perception. Previous studies in individuals
      diagnosed with Autism Spectrum Disorder (ASD) have uncovered characteristic
      patterns of visual processing that suggest they may rely more on enhanced local
      representations of individual objects instead of computing such perceptual
      averages. To further explore the fundamental nature of abstract statistical
      representation in visual perception, we investigated perceptual averaging of mean
      size in a group of 12 high-functioning individuals diagnosed with ASD using
      simplified versions of two identification and adaptation tasks that elicited
      characteristic perceptual averaging effects in a control group of neurotypical
      participants. In Experiment 1, participants performed with above chance accuracy
      in recalling the mean size of a set of circles (mean task) despite poor accuracy
      in recalling individual circle sizes (member task). In Experiment 2, their
      judgments of single circle size were biased by mean size adaptation. Overall,
      these results suggest that individuals with ASD perceptually average information
      about sets of objects in the surrounding environment. Our results underscore the
      fundamental nature of perceptual averaging in vision, and further our
      understanding of how autistic individuals make sense of the external environment.

PMID- 27872606
TI  - An Exploratory Study to Detect Meniere's Disease in Conventional MRI Scans Using
      Radiomics.
AB  - OBJECTIVE: The purpose of this exploratory study was to investigate whether a
      quantitative image analysis of the labyrinth in conventional magnetic resonance
      imaging (MRI) scans using a radiomics approach showed differences between
      patients with Meniere's disease (MD) and the control group. MATERIALS AND
      METHODS: In this retrospective study, MRI scans of the affected labyrinths of 24
      patients with MD were compared to the MRI scans of labyrinths of 29 patients with
      an idiopathic asymmetrical sensorineural hearing loss. The 1.5- and 3-T MRI scans
      had been previously made in a clinical setting between 2008 and 2015. 3D Slicer
      4.4 was used to extract several substructures of the labyrinth. A quantitative
      analysis of the normalized radiomic image features was performed in Mathematica
      10. The image features of the two groups were statistically compared. RESULTS:
      For numerous image features, there was a statistically significant difference (p
      value <0.05) between the MD group and the control group. The statistically
      significant differences in image features were localized in all the substructures
      of the labyrinth: 43 in the anterior semicircular canal, 10 in the vestibule, 22
      in the cochlea, 12 in the posterior semicircular canal, 24 in the horizontal
      semicircular canal, 11 in the common crus, and 44 in the volume containing the
      reuniting duct. Furthermore, some figures contain vertical or horizontal bands
      (three or more statistically significant image features in the same image
      feature). Several bands were seen: 9 bands in the anterior semicircular canal, 1
      band in the vestibule, 3 bands in the cochlea, 0 bands in the posterior
      semicircular canal, 5 bands in the horizontal semicircular canal, 3 bands in the
      common crus, and 10 bands in the volume containing the reuniting duct.
      CONCLUSION: In this exploratory study, several differences were found in image
      features between the MD group and the control group by using a quantitative
      radiomics approach on high resolution T2-weighted MRI scans of the labyrinth.
      Further research should be aimed at validating these results and translating them
      in a potential clinical diagnostic method to detect MD in MRI scans.

PMID- 27872605
TI  - Dissociating the Electrophysiological Correlates between Item Retrieval and
      Associative Retrieval in Associative Recognition: From the Perspective of
      Directed Forgetting.
AB  - Although many behavioral studies have reported associative memory was different
      from item memory, evidence coming from ERP researches has been in debate. In
      addition, directed forgetting effect for items has been fully discussed, but
      whether association between items can be directed-forgotten was unclear. The
      directed forgetting effect was important for dissociating the item retrieval and
      associative retrieval because of the one-to-one mapping relationship both between
      item retrieval and familiarity and between associative retrieval and
      recollection. Thus, the aim of this study was to investigate the dissociation
      between item retrieval and associative retrieval and test directed forgetting
      effect for associative information. Associative recognition paradigm combined
      with directed forgetting paradigm by ERP recording was employed. Old/rearranged
      effect in to-be-remembered condition, which was associated with associative
      memory, was significant at 500-800 ms (LPC) but not at 300-500 ms interval
      (FN400), indicating that item information was retrieved prior to associative
      information. The ERP wave calculated by subtracting the to-be-forgotten old pairs
      with "old" response from those with "rearranged" response, which reflected
      associative retrieval in the to-be-forgotten condition, was negative from 500 to
      800 ms (reversed old/new effect), indicating that association between items can
      be directed-forgotten. Similar evidence was obtained by contrasting "rearranged"
      responses aimed to the to-be-forgotten old pairs with those aimed to the to-be
      remembered rearranged pairs, which actually represented the complete failure of
      associative retrieval. Therefore, item retrieval and associative retrieval were
      indexed by FN400 and LPC respectively, with associative retrieval more inhibited
      than item retrieval.

PMID- 27872608
TI  - Clinical Assessment of Fatigability in Multiple Sclerosis: A Shift from
      Perception to Performance.

PMID- 27872607
TI  - Disparate Changes in Plasma and Brainstem Cytokine Levels in Adult and Ageing
      Rats Associated with Age-Related Changes in Facial Motor Neuron Number, Snout
      Muscle Morphology, and Exploratory Behavior.
AB  - An overall increase in inflammatory cytokines with age in both the blood and the
      central nervous system (CNS) has been proposed to explain many aspects of ageing,
      including decreased motor function and neurodegeneration. This study tests the
      hypothesis that age-related increases in inflammatory cytokines in the blood and
      CNS lead to facial motor neuron degeneration. Groups of 3-5 female Sprague-Dawley
      rats aged 3, 12-18, and 24 months were used. Twelve cytokines interleukin (IL)
      1alpha, IL-beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis
      factor-alpha (TNFalpha), interferon-gamma, and granulocyte macrophage-colony
      stimulating factor were measured in blood plasma and compared with those in the
      brainstem after first flushing blood from its vessels. The open-field test was
      used to measure exploratory behavior, and the morphology of the peripheral target
      muscle of facial motor neurons quantified. Total numbers of facial motor neurons
      were determined stereologically in separate groups of 3- and 24-month-old rats.
      Ageing rats showed a significant 30-42% decrease in blood plasma (peripheral)
      concentrations of IL-12p70 and TNFalpha and a significant 43-49% increase in
      brainstem (central) concentrations of IL-1alpha, IL-2, IL-4, IL-10, and TNFalpha.
      They also showed significant reductions in motor neuron number in the right but
      not left facial nucleus, reduced exploratory behavior, and increase in peripheral
      target muscle size. Marginal age-related facial motoneuronal loss occurs in the
      ageing rat and is characterized by complex changes in the inflammatory signature,
      rather than a general increase in inflammatory cytokines.

PMID- 27872609
TI  - Panitumumab-Associated Encephalopathy after Accidental Intra-arterial Application
      through Dislocated Central Venous Access Device.
AB  - Acute central nervous system (CNS) toxicity and immune-related side effects are
      increasingly recognized with the use of monoclonal antibodies for cancer therapy.
      Here, we report a patient who developed of acute-onset encephalopathy and coma,
      which began shortly after administration of panitumumab for the treatment of
      metastatic colorectal cancer. Echocardiography revealed that the drug had been
      infused into the left cardiac ventricle via a dislocated central venous line.
      Diffusion-weighted magnetic resonance imaging disclosed multiple cortical
      hyperintensities, which were preferentially located in the frontal lobes. While
      the neurological condition improved within a few days, the patient died 4 weeks
      later. It seems likely that the administration of the antibody via the intra
      arterial route contributed to the development of this condition. Toxic
      encephalopathy may be a hitherto unrecognized complication of panitumumab
      treatment and should be taken into consideration in patients developing CNS
      symptoms undergoing this therapy.

PMID- 27872611
TI  - Hypocholesterolemic and Prebiotic Effects of a Whole-Grain Oat-Based Granola
      Breakfast Cereal in a Cardio-Metabolic "At Risk" Population.
AB  - Meta-analyses of randomized controlled trials (RTC) have confirmed the
      hypocholesterolaemic effect of oats and oat based fibers. However, the mechanisms
      by which oats or oat fractions lower cholesterol is not totally clear.
      Recognizing the important role of the gut microbiome in metabolism and metabolic
      disease risk, we examined the impact of whole grain oat Granola (WGO) on the
      human gut microbiota and cardio-metabolic risk factors using a randomized
      crossover dietary intervention in at risk individuals (ClinicalTrials.gov
      Identifier: NCT01925365). We randomized 32 individuals at risk of developing
      cardio-metabolic disease by virtue of mild hypercholesterolaemia or glucose
      intolerance, into two groups consuming either 45 g of WGO or non-whole grain
      (NWG) breakfast cereals daily for two 6-week intervention periods separated by a
      4-week wash out period in a randomized, controlled, crossover, double-blinded
      design. Confirming the cholesterol lowering effect of WGO, we observed a
      significant time by treatment interaction, for total cholesterol (TC) (P =
      0.0001) and LDL-cholesterol (LDL-C) (P = 0.02) compared to NWG. A significant
      time by treatment interaction was also observed for the relative abundance of
      fecal bifidobacteria (P = 0.0001), lactobacilli (P = 0.001) and total bacterial
      count (P = 0.008), which were all elevated after consumption of WGO. Daily
      consumption of WGO resulted in a prebiotic effect on the human gut microbiota
      composition and significant reductions in TC and LDL-C concentrations. Prebiotic
      modulation of the human gut microbiota may thus constitute a previously
      unrecognized mechanism contributing to the hypocholesterolaemic effects of whole
      grain oat Granola.

PMID- 27872610
TI  - Relational Stability in the Expression of Normality, Variation, and Control of
      Thyroid Function.
AB  - Thyroid hormone concentrations only become sufficient to maintain a euthyroid
      state through appropriate stimulation by pituitary thyroid-stimulating hormone
      (TSH). In such a dynamic system under constant high pressure, guarding against
      overstimulation becomes vital. Therefore, several defensive mechanisms protect
      against accidental overstimulation, such as plasma protein binding, conversion of
      T4 into the more active T3, active transmembrane transport, counter-regulatory
      activities of reverse T3 and thyronamines, and negative hypothalamic-pituitary
      thyroid feedback control of TSH. TSH has gained a dominant but misguided role in
      interpreting thyroid function testing in assuming that its exceptional
      sensitivity thereby translates into superior diagnostic performance. However, TSH
      dependent thyroid disease classification is heavily influenced by statistical
      analytic techniques such as uni- or multivariate-defined normality. This demands
      a separation of its conjoint roles as a sensitive screening test and accurate
      diagnostic tool. Homeostatic equilibria (set points) in healthy subjects are less
      variable and do not follow a pattern of random variation, rather indicating signs
      of early and progressive homeostatic control across the euthyroid range. In the
      event of imminent thyroid failure with a reduced FT4 output per unit TSH,
      conversion efficiency increases in order to maintain FT3 stability. In such
      situations, T3 stability takes priority over set point maintenance. This suggests
      a concept of relational stability. These findings have important implications for
      both TSH reference limits and treatment targets for patients on levothyroxine.
      The use of archival markers is proposed to facilitate the homeostatic
      interpretation of all parameters.

PMID- 27872613
TI  - Rhamnolipids Produced by Indigenous Acinetobacter junii from Petroleum Reservoir
      and its Potential in Enhanced Oil Recovery.
AB  - Biosurfactant producers are crucial for incremental oil production in microbial
      enhanced oil recovery (MEOR) processes. The isolation of biosurfactant-producing
      bacteria from oil reservoirs is important because they are considered suitable
      for the extreme conditions of the reservoir. In this work, a novel biosurfactant
      producing strain Acinetobacter junii BD was isolated from a reservoir to reduce
      surface tension and emulsify crude oil. The biosurfactants produced by the strain
      were purified and then identified via electrospray ionization-Fourier transform
      ion cyclotron resonance mass spectrometry (ESI FT-ICR-MS). The biosurfactants
      generated by the strain were concluded to be rhamnolipids, the dominant
      rhamnolipids were C26H48O9, C28H52O9, and C32H58O13. The optimal carbon source
      and nitrogen source for biomass and biosurfactant production were NaNO3 and
      soybean oil. The results showed that the content of acid components increased
      with the progress of crude oil biodegradation. A glass micromodel test
      demonstrated that the strain significantly increased oil recovery through
      interfacial tension reduction, wettability alteration and the mobility of
      microorganisms. In summary, the findings of this study indicate that the newly
      developed BD strain and its metabolites have great potential in MEOR.

PMID- 27872614
TI  - Bioluminescent Vibrio fischeri Assays in the Assessment of Seasonal and Spatial
      Patterns in Toxicity of Contaminated River Sediments.
AB  - Several bacteria-based assays, notably Vibrio fischeri luminescence assays, are
      often used as environmental monitoring tool for toxicity in sediments that may
      serve as both sinks and secondary source of contamination in aquatic ecosystems.
      In this study, we used 30-s kinetic bioassays based on V. fischeri to evaluate
      the toxicity associated to sediments from five localities with different
      contamination inputs (Morava River and its tributary Drevnice River in the south
      eastern part of the Czech Republic). Toxicity assessed as half maximal inhibitory
      concentration (IC50) over the course of a year-long sampling was compared in
      bottom sediments and freshly trapped particulate material. Standard approach
      based on testing of aqueous elutriates was compared with toxicity of whole
      sediments (contact suspension toxicity). Bottom sediments showed lower toxicity
      compared to freshly trapped suspended materials in all cases. On the other hand,
      standardized elutriates induced generally weaker effects than suspended sediments
      likely due to losses during the extraction process. Toxicity generally increased
      during winter reaching maximum peaks in early spring months in all five sites.
      Total organic carbon (TOC) was found to be highly correlated with toxic effects.
      Toxicity from sites with direct industrial and agricultural water inputs also
      correlated with concentrations of metals, polycyclic aromatic hydrocarbons
      (PAHs), and polychlorinated biphenyls (PCBs). Single time point sampling followed
      by the extraction and testing of elutriates, do not truly reflect the spatial and
      temporal variability in natural sediments and may lead to underestimation of
      ecotoxic risks.

PMID- 27872612
TI  - Systems Biomedicine of Rabies Delineates the Affected Signaling Pathways.
AB  - The prototypical neurotropic virus, rabies, is a member of the Rhabdoviridae
      family that causes lethal encephalomyelitis. Although there have been a plethora
      of studies investigating the etiological mechanism of the rabies virus and many
      precautionary methods have been implemented to avert the disease outbreak over
      the last century, the disease has surprisingly no definite remedy at its late
      stages. The psychological symptoms and the underlying etiology, as well as the
      rare survival rate from rabies encephalitis, has still remained a mystery. We,
      therefore, undertook a systems biomedicine approach to identify the network of
      gene products implicated in rabies. This was done by meta-analyzing whole
      transcriptome microarray datasets of the CNS infected by strain CVS-11, and
      integrating them with interactome data using computational and statistical
      methods. We first determined the differentially expressed genes (DEGs) in each
      study and horizontally integrated the results at the mRNA and microRNA levels
      separately. A total of 61 seed genes involved in signal propagation system were
      obtained by means of unifying mRNA and microRNA detected integrated DEGs. We then
      reconstructed a refined protein-protein interaction network (PPIN) of infected
      cells to elucidate the rabies-implicated signal transduction network (RISN). To
      validate our findings, we confirmed differential expression of randomly selected
      genes in the network using Real-time PCR. In conclusion, the identification of
      seed genes and their network neighborhood within the refined PPIN can be useful
      for demonstrating signaling pathways including interferon circumvent, toward
      proliferation and survival, and neuropathological clue, explaining the intricate
      underlying molecular neuropathology of rabies infection and thus rendered a
      molecular framework for predicting potential drug targets.

PMID- 27872615
TI  - Microbial Communities of Conducting and Respiratory Zones of Lung-Transplanted
      Patients.
AB  - Background: Lung transplantation (LT) is a recognized treatment for end-stage
      pulmonary disease. Bacteria from the recipient nasopharynx seed the new lungs
      leading to infections and allograft damage. Understanding the characteristics and
      topological variations of the microbiota may be important to apprehend the
      pathophysiology of allograft dysfunction. Objectives: To examine the
      characteristics and relationship of bacterial compositions between conducting and
      respiratory zones of the allograft. Methods: We performed 16S rRNA gene
      sequencing on bronchial aspirates (BAs) and bronchoalveolar lavages (BALs)
      collected in pairs in 19 patients at several time-points post-LT. Results: The
      respiratory zone was characterized independently of the time post-LT by a higher
      bacterial richness than the conducting zone (p = 0.041). The phyla Firmicutes and
      Proteobacteria dominated both sampling zones, with an inverse correlation between
      these two phyla (Spearman r = -0.830). Samples of the same pair, as well as pairs
      from the same individual clustered together (Pseudo-F = 3.8652, p < 0.01).
      Microbiota of BA and BAL were more closely related in samples from the same
      patient than each sample type across different patients, with variation in
      community structure being mainly inter-individual (p < 0.01). Both number of
      antibiotics administered (p < 0.01) and time interval post-LT (p < 0.01)
      contributed to the variation in global microbiota structure. Longitudinal
      analysis of BA-BAL pairs of two patients showed dynamic wave like fluctuations of
      the microbiota. Conclusions: Our results show that post-transplant respiratory
      zones harbor higher bacterial richness, but overall similar bacterial profiles as
      compared to conductive zones. They further support an individual microbial
      signature following LT.

PMID- 27872616
TI  - Novel Approach for Evaluation of Bacteroides fragilis Protective Role against
      Bartonella henselae Liver Damage in Immunocompromised Murine Model.
AB  - Bartonella henselae is a gram-negative facultative intracellular bacterium and is
      the causative agent of cat-scratch disease. Our previous data have established
      that Bacteroides fragilis colonization is able to prevent B. henselae damages
      through the polysaccharide A (PSA) in an experimental murine model. In order to
      determine whether the PSA is essential for the protection against pathogenic
      effects of B. henselae in immunocompromised hosts, SCID mice were co-infected
      with B. fragilis wild type or its mutant B. fragilis DeltaPSA and the effects of
      infection on murine tissues have been observed by High-Frequency Ultrasound
      (HFUS), histopathological examination, and Transmission Electron Microscopy
      (TEM). For the first time, echostructure, hepatic lobes length, vascular
      alterations, and indirect signs of hepatic dysfunctions, routinely used as signs
      of disease in humans, have been analyzed in an immunocompromised murine model.
      Our findings showed echostructural alterations in all infected mice compared with
      the Phosphate Buffer Solution (PBS) control group; further, those infected with
      B. henselae and co-infected with B. henselae/B. fragilis DeltaPSA presented the
      major echostructural alterations. Half of the mice infected with B. henselae and
      all those co-infected with B. henselae/B. fragilis DeltaPSA have showed an
      altered hepatic echogenicity compared with the renal cortex. The echogenicity
      score of co-infected mice with B. henselae/B. fragilis DeltaPSA differed
      significantly compared with the PBS control group (p < 0.05). Moreover the
      inflammation score of the histopathological evaluation was fairly concordant with
      ultrasound findings. Ultrastructural analysis performed by TEM revealed no
      significant alterations in liver samples of SCID mice infected with B. fragilis
      wild type while those infected with B. fragilis DeltaPSA showed the presence of
      collagen around the main vessels compared with the PBS control group. The liver
      samples of mice infected with B. henselae showed macro-areas rich in collagen,
      stellate cells, and histiocytic cells. Interestingly, our data demonstrated that
      immunocompromised SCID mice infected with B. henselae and co-infected with B.
      henselae/B. fragilis DeltaPSA showed the most severe morpho-structural liver
      damage. In addition, these results suggests that the HFUS together with
      histopathological evaluation could be considered good imaging approach to
      evaluate hepatic alterations.

PMID- 27872618
TI  - Time Series Analysis of the Bacillus subtilis Sporulation Network Reveals Low
      Dimensional Chaotic Dynamics.
AB  - Chaotic behavior refers to a behavior which, albeit irregular, is generated by an
      underlying deterministic process. Therefore, a chaotic behavior is potentially
      controllable. This possibility becomes practically amenable especially when chaos
      is shown to be low-dimensional, i.e., to be attributable to a small fraction of
      the total systems components. In this case, indeed, including the major drivers
      of chaos in a system into the modeling approach allows us to improve
      predictability of the systems dynamics. Here, we analyzed the numerical
      simulations of an accurate ordinary differential equation model of the gene
      network regulating sporulation initiation in Bacillus subtilis to explore whether
      the non-linearity underlying time series data is due to low-dimensional chaos.
      Low-dimensional chaos is expectedly common in systems with few degrees of
      freedom, but rare in systems with many degrees of freedom such as the B. subtilis
      sporulation network. The estimation of a number of indices, which reflect the
      chaotic nature of a system, indicates that the dynamics of this network is
      affected by deterministic chaos. The neat separation between the indices obtained
      from the time series simulated from the model and those obtained from time series
      generated by Gaussian white and colored noise confirmed that the B. subtilis
      sporulation network dynamics is affected by low dimensional chaos rather than by
      noise. Furthermore, our analysis identifies the principal driver of the networks
      chaotic dynamics to be sporulation initiation phosphotransferase B (Spo0B). We
      then analyzed the parameters and the phase space of the system to characterize
      the instability points of the network dynamics, and, in turn, to identify the
      ranges of values of Spo0B and of the other drivers of the chaotic dynamics, for
      which the whole system is highly sensitive to minimal perturbation. In summary,
      we described an unappreciated source of complexity in the B. subtilis sporulation
      network by gathering evidence for the chaotic behavior of the system, and by
      suggesting candidate molecules driving chaos in the system. The results of our
      chaos analysis can increase our understanding of the intricacies of the
      regulatory network under analysis, and suggest experimental work to refine our
      behavior of the mechanisms underlying B. subtilis sporulation initiation control.

PMID- 27872617
TI  - Bacterial Genomics Reveal the Complex Epidemiology of an Emerging Pathogen in
      Arctic and Boreal Ungulates.
AB  - Northern ecosystems are currently experiencing unprecedented ecological change,
      largely driven by a rapidly changing climate. Pathogen range expansion, and
      emergence and altered patterns of infectious disease, are increasingly reported
      in wildlife at high latitudes. Understanding the causes and consequences of
      shifting pathogen diversity and host-pathogen interactions in these ecosystems is
      important for wildlife conservation, and for indigenous populations that depend
      on wildlife. Among the key questions are whether disease events are associated
      with endemic or recently introduced pathogens, and whether emerging strains are
      spreading throughout the region. In this study, we used a phylogenomic approach
      to address these questions of pathogen endemicity and spread for Erysipelothrix
      rhusiopathiae, an opportunistic multi-host bacterial pathogen associated with
      recent mortalities in arctic and boreal ungulate populations in North America. We
      isolated E. rhusiopathiae from carcasses associated with large-scale die-offs of
      muskoxen in the Canadian Arctic Archipelago, and from contemporaneous mortality
      events and/or population declines among muskoxen in northwestern Alaska and
      caribou and moose in western Canada. Bacterial genomic diversity differed
      markedly among these locations; minimal divergence was present among isolates
      from muskoxen in the Canadian Arctic, while in caribou and moose populations,
      strains from highly divergent clades were isolated from the same location, or
      even from within a single carcass. These results indicate that mortalities among
      northern ungulates are not associated with a single emerging strain of E.
      rhusiopathiae, and that alternate hypotheses need to be explored. Our study
      illustrates the value and limitations of bacterial genomic data for
      discriminating between ecological hypotheses of disease emergence, and highlights
      the importance of studying emerging pathogens within the broader context of
      environmental and host factors.

PMID- 27872620
TI  - Fungal Enolase, beta-Tubulin, and Chitin Are Detected in Brain Tissue from
      Alzheimer's Disease Patients.
AB  - Recent findings provide evidence that fungal structures can be detected in brain
      tissue from Alzheimer's disease (AD) patients using rabbit polyclonal antibodies
      raised against whole fungal cells. In the present work, we have developed and
      tested specific antibodies that recognize the fungal proteins, enolase and beta
      tubulin, and an antibody that recognizes the fungal polysaccharide chitin.
      Consistent with our previous studies, a number of rounded yeast-like and hyphal
      structures were detected using these antibodies in brain sections from AD
      patients. Some of these structures were intracellular and, strikingly, some were
      found to be located inside nuclei from neurons, whereas other fungal structures
      were detected extracellularly. Corporya amylacea from AD patients also contained
      enolase and beta-tubulin as revealed by these selective antibodies, but were
      devoid of fungal chitin. Importantly, brain sections from control subjects were
      usually negative for staining with the three antibodies. However, a few fungal
      structures can be observed in some control individuals. Collectively, these
      findings indicate the presence of two fungal proteins, enolase and beta-tubulin,
      and the polysaccharide chitin, in CNS tissue from AD patients. These findings are
      consistent with our hypothesis that AD is caused by disseminated fungal
      infection.

PMID- 27872619
TI  - Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction.
AB  - Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae
      capable of causing severe hemorrhagic fever with up to 80-90% mortality rates.
      The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over
      11,300 deaths; however, long-lasting persistence and recurrence in survivors has
      been documented, potentially leading to further transmission of the virus. We
      have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and
      Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs
      to naive recipient cells, resulting in an altered cellular activity. In the
      current manuscript, we examined the effect of Ebola structural proteins VP40, GP,
      NP and VLPs on recipient immune cells, as well as the effect of exosomes
      containing these proteins on naive immune cells. We found that VP40-transfected
      cells packaged VP40 into exosomes, and that these exosomes were capable of
      inducing apoptosis in recipient immune cells. Additionally, we show that presence
      of VP40 within parental cells or in exosomes delivered to naive cells could
      result in the regulation of RNAi machinery including Dicer, Drosha, and Ago 1,
      which may play a role in the induction of cell death in recipient immune cells.
      Exosome biogenesis was regulated by VP40 in transfected cells by increasing
      levels of ESCRT-II proteins EAP20 and EAP45, and exosomal marker proteins CD63
      and Alix. VP40 was phosphorylated by Cdk2/Cyclin complexes at Serine 233 which
      could be reversed with r-Roscovitine treatment. The level of VP40-containing
      exosomes could also be regulated by treated cells with FDA-approved
      Oxytetracycline. Additionally, we utilized novel nanoparticles to safely capture
      VP40 and other viral proteins from Ebola VLPs spiked into human samples using
      SDS/reducing agents, thus minimizing the need for BSL-4 conditions for most
      downstream assays. Collectively, our data indicates that VP40 packaged into
      exosomes may be responsible for the deregulation and eventual destruction of the
      T-cell and myeloid arms of the immune system (bystander lymphocyte apoptosis),
      allowing the virus to replicate to high titers in the immunocompromised host.
      Moreover, our results suggest that the use of drugs such as Oxytetracycline to
      modulate the levels of exosomes exiting EBOV-infected cells may be able to
      prevent the devastation of the adaptive immune system and allow for an improved
      rate of survival.

PMID- 27872621
TI  - Combining Theoretical and Experimental Techniques to Study Murine Heart
      Transplant Rejection.
AB  - The quality of life of organ transplant recipients is compromised by
      complications associated with life-long immunosuppression, such as hypertension,
      diabetes, opportunistic infections, and cancer. Moreover, the absence of
      established tolerance to the transplanted tissues causes limited long-term graft
      survival rates. Thus, there is a great medical need to understand the complex
      immune system interactions that lead to transplant rejection so that novel and
      effective strategies of intervention that redirect the system toward transplant
      acceptance (while preserving overall immune competence) can be identified. This
      study implements a systems biology approach in which an experimentally based
      mathematical model is used to predict how alterations in the immune response
      influence the rejection of mouse heart transplants. Five stages of conventional
      mouse heart transplantation are modeled using a system of 13 ordinary
      differential equations that tracks populations of both innate and adaptive
      immunity as well as proxies for pro- and anti-inflammatory factors within the
      graft and a representative draining lymph node. The model correctly reproduces
      known experimental outcomes, such as indefinite survival of the graft in the
      absence of CD4+ T cells and quick rejection in the absence of CD8+ T cells. The
      model predicts that decreasing the translocation rate of effector cells from the
      lymph node to the graft delays transplant rejection. Increasing the starting
      number of quiescent regulatory T cells in the model yields a significant but
      somewhat limited protective effect on graft survival. Surprisingly, the model
      shows that a delayed appearance of alloreactive T cells has an impact on graft
      survival that does not correlate linearly with the time delay. This computational
      model represents one of the first comprehensive approaches toward simulating the
      many interacting components of the immune system. Despite some limitations, the
      model provides important suggestions of experimental investigations that could
      improve the understanding of rejection. Overall, the systems biology approach
      used here is a first step in predicting treatments and interventions that can
      induce transplant tolerance while preserving the capacity of the immune system to
      protect against legitimate pathogens.

PMID- 27872622
TI  - An Evaluation of 20 Years of EU Framework Programme-Funded Immune-Mediated
      Inflammatory Translational Research in Non-Human Primates.
AB  - Aging western societies are facing an increasing prevalence of chronic
      inflammatory and degenerative diseases for which often no effective treatments
      exist, resulting in increasing health-care expenditure. Despite high investments
      in drug development, the number of promising new drug candidates decreases. We
      propose that preclinical research in non-human primates can help to bridge the
      gap between drug discovery and drug prescription. Translational research covers
      various stages of drug development of which preclinical efficacy tests in valid
      animal models is usually the last stage. Preclinical research in non-human
      primates may be essential in the evaluation of new drugs or therapies when a
      relevant rodent model is not available. Non-human primate models for life
      threatening or severely debilitating diseases in humans are available at the
      Biomedical Primate Research Centre (BPRC). These have been instrumental in
      translational research for several decades. In order to stimulate European health
      research and innovation from bench to bedside, the European Commission has
      invested heavily in access to non-human primate research for more than 20 years.
      BPRC has hosted European users in a series of transnational access programs
      covering a wide range of research areas with the common theme being immune
      mediated inflammatory disorders. We present an overview of the results and give
      an account of the studies performed as part of European Union Framework Programme
      (EU FP)-funded translational non-human primate research performed at the BPRC.
      These data illustrate the value of translational non-human primate research for
      the development of new therapies and emphasize the importance of EU FP funding in
      drug development.

PMID- 27872624
TI  - Diagnostics of Primary Immunodeficiencies through Next-Generation Sequencing.
AB  - BACKGROUND: Recently, a growing number of novel genetic defects underlying
      primary immunodeficiencies (PIDs) have been identified, increasing the number of
      PID up to more than 250 well-defined forms. Next-generation sequencing (NGS)
      technologies and proper filtering strategies greatly contributed to this rapid
      evolution, providing the possibility to rapidly and simultaneously analyze large
      numbers of genes or the whole exome. OBJECTIVE: To evaluate the role of targeted
      NGS and whole exome sequencing (WES) in the diagnosis of a case series,
      characterized by complex or atypical clinical features suggesting a PID,
      difficult to diagnose using the current diagnostic procedures. METHODS: We
      retrospectively analyzed genetic variants identified through targeted NGS or WES
      in 45 patients with complex PID of unknown etiology. RESULTS: Forty-seven
      variants were identified using targeted NGS, while 5 were identified using WES.
      Newly identified genetic variants were classified into four groups: (I)
      variations associated with a well-defined PID, (II) variations associated with
      atypical features of a well-defined PID, (III) functionally relevant variations
      potentially involved in the immunological features, and (IV) non-diagnostic
      genotype, in whom the link with phenotype is missing. We reached a conclusive
      genetic diagnosis in 7/45 patients (~16%). Among them, four patients presented
      with a typical well-defined PID. In the remaining three cases, mutations were
      associated with unexpected clinical features, expanding the phenotypic spectrum
      of typical PIDs. In addition, we identified 31 variants in 10 patients with
      complex phenotype, individually not causative per se of the disorder. CONCLUSION:
      NGS technologies represent a cost-effective and rapid first-line genetic approach
      for the evaluation of complex PIDs. WES, despite a moderate higher cost compared
      to targeted, is emerging as a valuable tool to reach in a timely manner, a PID
      diagnosis with a considerable potential to draw genotype-phenotype correlation.
      Nevertheless, a large fraction of patients still remains without a conclusive
      diagnosis. In these patients, the sum of non-diagnostic variants might be proven
      informative in future studies with larger cohorts of patients.

PMID- 27872623
TI  - Malaria Parasites: The Great Escape.
AB  - Parasites of the genus Plasmodium have a complex life cycle. They alternate
      between their final mosquito host and their intermediate hosts. The parasite can
      be either extra- or intracellular, depending on the stage of development. By
      modifying their shape, motility, and metabolic requirements, the parasite adapts
      to the different environments in their different hosts. The parasite has evolved
      to escape the multiple immune mechanisms in the host that try to block parasite
      development at the different stages of their development. In this article, we
      describe the mechanisms reported thus far that allow the Plasmodium parasite to
      evade innate and adaptive immune responses.

PMID- 27872626
TI  - Antigen-Presenting Cells and Antigen Presentation in Tertiary Lymphoid Organs.
AB  - Tertiary lymphoid organs (TLOs) form in territorialized niches of peripheral
      tissues characterized by the presence of antigens; however, little is known about
      mechanism(s) of antigen handling by ectopic lymphoid structures. In this mini
      review, we will discuss the role of antigen-presenting cells and mechanisms of
      antigen presentation in TLOs, summarizing what is currently known about this
      facet of the formation and function of these tissues as well as identifying
      questions yet to be addressed.

PMID- 27872625
TI  - Effect of CMV and Aging on the Differential Expression of CD300a, CD161, T-bet,
      and Eomes on NK Cell Subsets.
AB  - Natural killer (NK) cells are innate lymphoid cells involved in the defense
      against virus-infected cells and tumor cells. NK cell phenotype and function is
      affected with age and cytomegalovirus (CMV) latent infection. Aging affects the
      frequency and phenotype of NK cells, and CMV infection also contributes to these
      alterations. Thus, a reduction of CD56bright NK cell subpopulation associated
      with age and an expansion of memory-like NK cells CD56dimCD57+NKG2C+ probably
      related to CMV seropositivity have been described. NK cells express T-bet and
      Eomes transcription factors that are necessary for the development of NK cells.
      Here, we analyze the effect of age and CMV seropositivity on the expression of
      CD300a and CD161 inhibitory receptors, and T-bet and Eomes transcription factors
      in NK cell subsets defined by the expression of CD56 and CD57. CD300a is
      expressed by the majority of NK cells. CD56bright NK cells express higher levels
      of CD300a than CD56dim NK cells. An increase in the expression of CD300a was
      associated with age, whereas a decreased expression of CD161 in CD56dim NK cells
      was associated with CMV seropositivity. In CD56dim NK cells, an increased
      percentage of CD57+CD300a+ and a reduction in the percentage of CD161+CD300a+
      cells were found to be associated with CMV seropositivity. Regarding T-bet and
      Eomes transcription factors, CMV seropositivity was associated with a decrease of
      T-bethi in CD56dimCD57+ NK cells from young individuals, whereas Eomes expression
      was increased with CMV seropositivity in both CD56bright and CD56dimCD57+/- (from
      middle age and young individuals, respectively) and was decreased with aging in
      all NK subsets from the three group of age. In conclusion, CMV infection and age
      induce significant changes in the expression of CD300a and CD161 in NK cell
      subsets defined by the expression of CD56 and CD57. T-bet and Eomes are
      differentially expressed on NK cell subsets, and their expression is affected by
      CMV latent infection and aging.

PMID- 27872628
TI  - Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the
      Involvement of a MADS-Box Gene, MdMADS1.
AB  - Skin color is a key quality attribute of fruits and how to improve fruit
      coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural
      plant growth regulator, can significantly increase anthocyanin accumulation in
      fruit skin and therefore effectively improve coloration of many fruits, including
      apple. However, the molecular mechanism how ALA stimulates anthocyanin
      accumulation in fruit skin remains unknown. Here, we investigated the impact of
      ALA on apple skin at the protein and mRNA levels. A total of 85 differentially
      expressed proteins in apple skins between ALA and water treatment (control) were
      identified by complementary gel-based and gel-free separation techniques. Most of
      these differentially expressed proteins were up-regulated by ALA. Function
      analysis suggested that 87.06% of the ALA-responsive proteins were associated
      with fruit ripening. To further screen ALA-responsive regulators, we constructed
      a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained
      104 differentially expressed unigenes, of which 38 unigenes were indicators for
      the fruit ripening-related genes. The differentially changed proteins and
      transcripts did not correspond well at an individual level, but showed similar
      regulated direction in function at the pathway level. Among the identified fruit
      ripening-related genes, the expression of MdMADS1, a developmental transcription
      regulator of fruit ripening, was positively correlated with expression of
      anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX, and MdUFGT) in apple skin
      under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin
      content in transformed apple calli, which was further enhanced by ALA. The
      anthocyanin content in MdMADS1-silenced calli was less than that in the control
      with ALA treatment, but higher than that without ALA treatment. These results
      indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In
      addition, anthocyanin-related verification in apple calli suggested that the
      regulation of MdMADS1 on anthocyanin biosynthesis was partially independent of
      fruit ripening process. Taken together, our findings provide insight into the
      mechanism how ALA regulates anthocyanin accumulation and add new information on
      transcriptase regulators of fruit coloration.

PMID- 27872627
TI  - Stress and Non-Stress Roles of Inflammatory Signals during HSC Emergence and
      Maintenance.
AB  - Hematopoietic stem cells (HSCs) are a rare population that gives rise to almost
      all cells of the hematopoietic system, including immune cells. Until recently, it
      was thought that immune cells sense inflammatory signaling and HSCs respond only
      secondarily to these signals. However, it was later shown that adult HSCs could
      directly sense and respond to inflammatory signals, resulting in a higher output
      of immune cells. Recent studies demonstrated that inflammatory signaling is also
      vital for HSC ontogeny. These signals are thought to arise in the absence of
      pathogens, are active during development, and indispensable for HSC formation. In
      contrast, during times of stress and disease, inflammatory responses can be
      activated and can have devastating effects on HSCs. In this review, we summarize
      the current knowledge about inflammatory signaling in HSC development and
      maintenance, as well as the endogenous molecular cues that can trigger
      inflammatory pathway activation. Finally, we comment of the role of inflammatory
      signaling in hematopoietic diseases.

PMID- 27872629
TI  - QTL Analysis of Spike Morphological Traits and Plant Height in Winter Wheat
      (Triticum aestivum L.) Using a High-Density SNP and SSR-Based Linkage Map.
AB  - Wheat yield can be enhanced by modifying the spike morphology and the plant
      height. In this study, a population of 191 F9 recombinant inbred lines (RILs) was
      developed from a cross between two winter cultivars Yumai 8679 and Jing 411. A
      dense genetic linkage map with 10,816 markers was constructed by incorporating
      single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) marker
      information. Five spike morphological traits and plant height were evaluated
      under nine environments for the RILs and parental lines, and the number of
      detected environmentally stable QTLs were 18 and three, respectively. The 1RS/1BL
      (rye) translocation increased both spike length and spikelet number with constant
      spikelet compactness. The QPht.cau-2D.1 was identical to gene Rht8, which
      decreased spike length without modifying spikelet number. Notably, four novel
      QTLs locating on chromosomes 1AS (QSc.cau-1A.1), 2DS (QSc.cau-2D.1), and 7BS
      (QSl.cau-7B.1 and QSl.cau-7B.2) were firstly identified in this study, which
      provide further insights into the genetic factors that shaped the spike
      morphology in wheat. Moreover, SNP markers tightly linked to previously reported
      QTLs will eventually facilitate future studies including their positional cloning
      or marker-assisted selection.

PMID- 27872630
TI  - Control of Wilt and Rot Pathogens of Tomato by Antagonistic Pink Pigmented
      Facultative Methylotrophic Delftia lacustris and Bacillus spp.
AB  - The studies on the biocontrol potential of pink pigmented facultative
      methylotrophic (PPFM) bacteria other than the genus Methylobacterium are scarce.
      In the present study, we report three facultative methylotrophic isolates; PPO-1,
      PPT-1, and PPB-1, respectively, identified as Delftia lacustris, Bacillus
      subtilis, and Bacillus cereus by 16S rRNA gene sequence analysis. Hemolytic
      activity was tested to investigate the potential pathogenicity of isolates to
      plants and humans, the results indicates that the isolates PPO-1, PPT-1, and PPB
      1 are not pathogenic strains. Under in vitro conditions, D. lacustris PPO-1, B.
      subtilis PPT-1, and B. cereus PPB-1 showed direct antagonistic effect by
      inhibiting the mycelial growth of fungal pathogens; Fusarium oxysporum f. sp.
      lycopersici (2.15, 2.05, and 1.95 cm), Sclerotium rolfsii (2.14, 2.04, and 1.94
      cm), Pythium ultimum (2.12, 2.02, and 1.92 cm), and Rhizoctonia solani (2.18,
      2.08, and 1.98 cm) and also produced volatile inhibitory compounds. Under plant
      growth chamber condition methylotrophic bacterial isolates; D. lacustris PPO-1,
      B. subtilis PPT-1, and B. cereus PPB-1 significantly reduced the disease
      incidence of tomato. Under greenhouse condition, D. lacustris PPO-1, B. subtilis
      PPT-1, and B. cereus PPB-1 inoculated tomato plants, when challenged with F.
      oxysporum f. sp. lycopersici, S. rolfsii, P. ultimum, and R. solani, increased
      the pathogenesis related proteins (beta-1,3-glucanase and chitinase) and defense
      enzymes (phenylalanine ammonia lyase, peroxidase, polyphenol oxidase, and
      catalase) on day 5 after inoculation. In the current study, we first report the
      facultative methylotrophy in pink pigmented D. lacustris, B. subtilis, and B.
      cereus and their antagonistic potential against fungal pathogens. Direct
      antagonistic and ISR effects of these isolates against fungal pathogens of tomato
      evidenced their possible use as a biocontrol agent.

PMID- 27872631
TI  - Identification and Characterization of CYC-Like Genes in Regulation of Ray Floret
      Development in Chrysanthemum morifolium.
AB  - Chrysanthemum morifolium, one of the most economically important ornamental crops
      worldwide, is well-known for the elaborate and complex inflorescence which is
      composed of both bilaterally symmetrical ray florets and radially symmetrical
      disc florets. Despite continuing efforts, the molecular mechanisms underlying
      regulation of the two flower types are still unclear so far. CYC-like proteins
      have been shown to control flower symmetry or regulate flower-type identity in
      several angiosperm plant lineages. In this study, we conducted comparative
      analysis of the CmCYC2 genes in two chrysanthemum cultivars and their F1
      progenies with various whorls of ray florets. Six CmCYC genes were identified and
      sequenced, all of which were grouped into the CYC2 subclade. All the six CmCYC2
      genes were predominantly expressed in reproductive organs, and in particular in
      the petal of ray florets. Of these genes, the transcription level of CmCYC2c was
      highly up-regulated in ray florets of the double-ray flowered heads. In addition,
      the result that CmCYC2c was highly expressed at key developing stages indicates
      its role in regulating petal development. Furthermore, overexpression of CmCYC2c
      in C. lavandulifolium, one of the original species of C. morifolium, led to
      significant increase in flower numbers and petal ligule length of ray florets.
      Besides CmCYC2c, the expression of CmCYC2f was also significantly up-regulated in
      transgenic lines, implying a possible role in regulating development of ray
      florets. Both results of expression patterns and transgenic phenotypes suggest
      that CmCYC2c is involved in regulating ray floret identity in the chrysanthemum.
      This study will be useful for genetic manipulation of flower shape in
      chrysanthemum and hence promote the process of molecular breeding.

PMID- 27872632
TI  - Three Rice NAC Transcription Factors Heteromerize and Are Associated with Seed
      Size.
AB  - NACs are plant-specific transcription factors (TFs) involved in multiple aspects
      of development and stress. In rice, three NAC TF encoding genes, namely ONAC020,
      ONAC026, and ONAC023 express specifically during seed development, at extremely
      high levels. They exhibit significantly strong association with seed size/weight
      with the sequence variations located in the upstream regulatory region.
      Concomitantly, their expression pattern/levels during seed development vary
      amongst different accessions with variation in seed size. The alterations in the
      promoter sequences of the three genes, amongst the five rice accessions,
      correlate with the expression levels to a certain extent only. In terms of
      transcriptional properties, the three NAC TFs can activate and/or suppress
      downstream genes, though to different extents. Only ONAC026 is localized to the
      nucleus while ONAC020 and ONAC023 are targeted to the ER and cytoplasm,
      respectively. Interestingly, these two proteins interact with ONAC026 and the
      dimers localize in the nucleus. Trans-splicing between ONAC020 and ONAC026
      results in three additional forms of ONAC020. The transcriptional properties
      including activation, repression, subcellular localization and heterodimerization
      of trans-spliced forms of ONAC020 and ONAC026 are different, indicating toward
      their role as competitors. The analysis presented in this paper helps to conclude
      that the three NAC genes, which are associated with seed size, have independent
      as well as overlapping roles during the process and can be exploited as potential
      targets for crop improvement.

PMID- 27872633
TI  - A Factor Linking Floral Organ Identity and Growth Revealed by Characterization of
      the Tomato Mutant unfinished flower development (ufd).
AB  - Floral organogenesis requires coordinated interactions between genes specifying
      floral organ identity and those regulating growth and size of developing floral
      organs. With the aim to isolate regulatory genes linking both developmental
      processes (i.e., floral organ identity and growth) in the tomato model species, a
      novel mutant altered in the formation of floral organs was further characterized.
      Under normal growth conditions, floral organ primordia of mutant plants were
      correctly initiated, however, they were unable to complete their development
      impeding the formation of mature and fertile flowers. Thus, the growth of floral
      buds was blocked at an early stage of development; therefore, we named this
      mutant as unfinished flower development (ufd). Genetic analysis performed in a
      segregating population of 543 plants showed that the abnormal phenotype was
      controlled by a single recessive mutation. Global gene expression analysis
      confirmed that several MADS-box genes regulating floral identity as well as other
      genes participating in cell division and different hormonal pathways were
      affected in their expression patterns in ufd mutant plants. Moreover, ufd mutant
      inflorescences showed higher hormone contents, particularly ethylene precursor 1
      aminocyclopropane-1-carboxylic acid (ACC) and strigol compared to wild type. Such
      results indicate that UFD may have a key function as positive regulator of the
      development of floral primordia once they have been initiated in the four floral
      whorls. This function should be performed by affecting the expression of floral
      organ identity and growth genes, together with hormonal signaling pathways.

PMID- 27872634
TI  - CHLH/GUN5 Function in Tetrapyrrole Metabolism Is Correlated with Plastid
      Signaling but not ABA Responses in Guard Cells.
AB  - Expression of Photosynthesis-Associated Nuclear Genes (PhANGs) is controlled by
      environmental stimuli and plastid-derived signals ("plastid signals")
      transmitting the developmental and functional status of plastids to the nucleus.
      Arabidopsis genomes uncoupled (gun) mutants exhibit defects in plastid signaling,
      leading to ectopic expression of PhANGs in the absence of chloroplast
      development. GUN5 encodes the plastid-localized Mg-chelatase enzyme subunit
      (CHLH), and recent studies suggest that CHLH is a multifunctional protein
      involved in tetrapyrrole biosynthesis, plastid signaling and ABA responses in
      guard cells. To understand the basis of CHLH multifunctionality, we investigated
      15 gun5 missense mutant alleles and transgenic lines expressing a series of
      truncated CHLH proteins in a severe gun5 allele (cch) background (tCHLHs, 10
      different versions). Here, we show that Mg-chelatase function and plastid
      signaling are generally correlated; in contrast, based on the analysis of the
      gun5 missense mutant alleles, ABA-regulated stomatal control is distinct from
      these two other functions. We found that none of the tCHLHs could restore plastid
      signaling or Mg-chelatase functions. Additionally, we found that both the C
      terminal half and N-terminal half of CHLH function in ABA-induced stomatal
      movement.

PMID- 27872636
TI  - Analyzing Brain Functions by Subject Classification of Functional Near-Infrared
      Spectroscopy Data Using Convolutional Neural Networks Analysis.
AB  - Functional near-infrared spectroscopy (fNIRS) is suitable for noninvasive mapping
      of relative changes in regional cortical activity but is limited for quantitative
      comparisons among cortical sites, subjects, and populations. We have developed a
      convolutional neural network (CNN) analysis method that learns feature vectors
      for accurate identification of group differences in fNIRS responses. In this
      study, subject gender was classified using CNN analysis of fNIRS data. fNIRS data
      were acquired from male and female subjects during a visual number memory task
      performed in a white noise environment because previous studies had revealed that
      the pattern of cortical blood flow during the task differed between males and
      females. A learned classifier accurately distinguished males from females based
      on distinct fNIRS signals from regions of interest (ROI) including the inferior
      frontal gyrus and premotor areas that were identified by the learning algorithm.
      These cortical regions are associated with memory storage, attention, and task
      motor response. The accuracy of the classifier suggests stable gender-based
      differences in cerebral blood flow during this task. The proposed CNN analysis
      method can objectively identify ROIs using fNIRS time series data for machine
      learning to distinguish features between groups.

PMID- 27872635
TI  - Rhizosphere Organic Anions Play a Minor Role in Improving Crop Species' Ability
      to Take Up Residual Phosphorus (P) in Agricultural Soils Low in P Availability.
AB  - Many arable lands have accumulated large reserves of residual phosphorus (P) and
      a relatively large proportion of soil P is less available for uptake by plants.
      Root released organic anions are widely documented as a key physiological
      strategy to enhance P availability, while limited information has been generated
      on the contribution of rhizosphere organic anions to P utilization by crops grown
      in agricultural soils that are low in available P and high in extractable Ca, Al,
      and Fe. We studied the role of rhizosphere organic anions in P uptake from
      residual P in four common crops Triticum aestivum, Avena sativa, Solanum
      tuberosum, and Brassica napus in low- and high-P availability agricultural soils
      from long-term fertilization field trials in a mini-rhizotron experiment with
      four replications. Malate was generally the dominant organic anion. More
      rhizosphere citrate was detected in low P soils than in high P soil. B. napus
      showed 74-103% increase of malate in low P loam, compared with clay loam. A.
      sativa had the greatest rhizosphere citrate concentration in all soils (5.3-15.2
      MUmol g-1 root DW). A. sativa also showed the highest level of root colonization
      by arbuscular mycorrhizal fungi (AMF; 36 and 40%), the greatest root mass ratio
      (0.51 and 0.66) in the low-P clay loam and loam respectively, and the greatest
      total P uptake (5.92 mg P/mini-rhizotron) in the low-P loam. B. napus had 15-44%
      more rhizosphere acid phosphatase (APase) activity, ~0.1-0.4 units lower
      rhizosphere pH than other species, the greatest increase in rhizosphere water
      soluble P in the low-P soils, and the greatest total P uptake in the low-P clay
      loam. Shoot P content was mainly explained by rhizosphere APase activity, water
      soluble P and pH within low P soils across species. Within species, P uptake was
      mainly linked to rhizosphere water soluble P, APase, and pH in low P soils. The
      effects of rhizosphere organic anions varied among species and they appeared to
      play minor roles in improving P availability and uptake.

PMID- 27872637
TI  - Key Technology of Real-Time Road Navigation Method Based on Intelligent Data
      Research.
AB  - The effect of traffic flow prediction plays an important role in routing
      selection. Traditional traffic flow forecasting methods mainly include linear,
      nonlinear, neural network, and Time Series Analysis method. However, all of them
      have some shortcomings. This paper analyzes the existing algorithms on traffic
      flow prediction and characteristics of city traffic flow and proposes a road
      traffic flow prediction method based on transfer probability. This method first
      analyzes the transfer probability of upstream of the target road and then makes
      the prediction of the traffic flow at the next time by using the traffic flow
      equation. Newton Interior-Point Method is used to obtain the optimal value of
      parameters. Finally, it uses the proposed model to predict the traffic flow at
      the next time. By comparing the existing prediction methods, the proposed model
      has proven to have good performance. It can fast get the optimal value of
      parameters faster and has higher prediction accuracy, which can be used to make
      real-time traffic flow prediction.

PMID- 27872639
TI  - Histogram of Oriented Gradient Based Gist Feature for Building Recognition.
AB  - We proposed a new method of gist feature extraction for building recognition and
      named the feature extracted by this method as the histogram of oriented gradient
      based gist (HOG-gist). The proposed method individually computes the normalized
      histograms of multiorientation gradients for the same image with four different
      scales. The traditional approach uses the Gabor filters with four angles and four
      different scales to extract orientation gist feature vectors from an image. Our
      method, in contrast, uses the normalized histogram of oriented gradient as
      orientation gist feature vectors of the same image. These HOG-based orientation
      gist vectors, combined with intensity and color gist feature vectors, are the
      proposed HOG-gist vectors. In general, the HOG-gist contains four
      multiorientation histograms (four orientation gist feature vectors), and its
      texture description ability is stronger than that of the traditional gist using
      Gabor filters with four angles. Experimental results using Sheffield Buildings
      Database verify the feasibility and effectiveness of the proposed HOG-gist.

PMID- 27872638
TI  - A Cognitive Model Based on Neuromodulated Plasticity.
AB  - Associative learning, including classical conditioning and operant conditioning,
      is regarded as the most fundamental type of learning for animals and human
      beings. Many models have been proposed surrounding classical conditioning or
      operant conditioning. However, a unified and integrated model to explain the two
      types of conditioning is much less studied. Here, a model based on neuromodulated
      synaptic plasticity is presented. The model is bioinspired including multistored
      memory module and simulated VTA dopaminergic neurons to produce reward signal.
      The synaptic weights are modified according to the reward signal, which simulates
      the change of associative strengths in associative learning. The experiment
      results in real robots prove the suitability and validity of the proposed model.

PMID- 27872640
TI  - Nucleotide Analogue-Related Proximal Renal Tubular Dysfunction during Long-Term
      Treatment of Chronic Hepatitis B: A Cross-Sectional Study.
AB  - Background. There have been few reports of nucleotide analogue-related renal
      tubular dysfunction (RTD) in CHB patients. We assessed the prevalence and
      presentation of nucleotide analogue-related proximal RTD. Methods. A cross
      sectional study was performed in CHB patients taking nucleotide analogues.
      Inclusion criteria were patients who were on adefovir or tenofovir as mono- or
      add-on therapy with lamivudine (LAM) >1 year. Serum and urine were collected.
      Fractional excretion of phosphate (FEPO4), uric acid (FEUA), and potassium was
      calculated. Renal losses were defined based on the criteria: protein (24-hour
      urine protein >150 mg), glucose (glycosuria with normoglycemia), phosphate (FEPO4
      >18%), uric acid (FEUA >15%), potassium (renal potassium losses with
      hypokalemia), and bicarbonate (normal gap acidosis). Subclinical and overt
      proximal RTD were defined when 2 and >=3 criteria presented. Results. Ninety-two
      patients were enrolled. The mean duration of nucleotide analogue taking was 55.1
      +/- 29.6 months. Proximal RTD was found in 24 (26.1%) patients (subclinical 15
      (16.3%) and overt 9 (9.8%)). The severity of RTD was associated with the duration
      of nucleotide analogue (P = 0.01). Conclusions. The prevalence of proximal RTD in
      CHB patients taking nucleotide analogues was 26%. The severity of RTD was
      associated with the treatment duration. Comprehensive testing is necessary for
      early detecting nucleotide analogue-related nephrotoxicity.

PMID- 27872641
TI  - Muscle Functions and Functional Performance among Older Persons with and without
      Low Back Pain.
AB  - This study aims to compare muscle functions and functional performances between
      older persons with and without low back pain (LBP) and to determine the
      association between muscle functions and functional performances. This is a cross
      sectional study, involving 95 older persons (age = 70.27 +/- 7.26 years).
      Anthropometric characteristics, muscle functions, and functional performances
      were measured. Data were analyzed using ANOVA, Pearson's correlation, and
      multiple linear regression. The functional performances showed no significant
      differences (females LBP versus non-LBP, males LBP versus non-LBP) (p < 0.05).
      For muscle functions, significant differences were found (females LBP versus non
      LBP) for abdominal muscle strength (p = 0.006) and back muscle strength (p =
      0.07). In the LBP group, significant correlations were found between back and
      abdominal muscle strength and hand grip strength (r = 0.377 and r = 0.396,
      resp.), multifidus control and lower limb function (r = 0.363) in females, and
      back muscle strength and lower limb function (r = 0.393) in males (all p < 0.05).
      Regression analysis showed that abdominal and back muscle strengths were
      significant predictors of hand grip strength (p = 0.041 and p = 0.049, resp.),
      and multifidus control was a significant predictor of lower limb function in
      females (p = 0.047). This study demonstrates that older women with LBP exhibit
      poorer muscle functions compared to older women without LBP.

PMID- 27872642
TI  - Rationale and Design of RNAFH Study: Effect of Rosuvastatin (10 mg/d) on
      Nonalcoholic Fatty Liver in Metabolic Syndrome Patients without Overt Diabetes
      Evaluated by 1H-Magnetic Resonance Spectroscopy.
AB  - Objective. The RNAFH study (effect of rosuvastatin on nonalcoholic fatty liver
      disease in metabolic syndrome patients without overt diabetes evaluated by 1H
      MRS) is a prospective randomized, single-center, open-label trail designed to
      assess the effect of rosuvastatin on the intrahepatocellular lipid (IHCL) level
      of nonalcoholic fatty liver disease (NAFLD). Methods. 40 NAFLD patients meeting
      inclusion and exclusion criteria with metabolic syndrome (MS) but without overt
      diabetes mellitus will be included. Patients will be randomized to 52-week
      treatment with either rosuvastatin (10 mg/d) or blank control. The primary end
      point is IHCL evaluated by 1H-MRS, which was considered to be the most accurate
      noninvasive method for the evaluation of NAFLD. Secondary end points include
      homeostasis model assessment of insulin resistance (HOMA-IR) index on behalf of
      insulin resistance level and lipid parameters. Safety indicators will be
      monitored such as liver function, renal function, muscle stability, and glucose
      metabolism. The aims of the present study are noteworthy in respect that (1) IHCL
      is a quantitative indicator for evaluating the degree of fatty liver disease and
      1H-MRS is a noninvasive technique to provide this specific index precisely, (2)
      meanwhile the HOMA-IR index and lipid parameters will be monitored, and (3) the
      safety of rosuvastatin treatment for 52 weeks will be evaluated including glucose
      metabolism, muscle stability, liver function, and renal function.

PMID- 27872643
TI  - Antibiotic Susceptibility Patterns of Bacterial Isolates from Pus Samples in a
      Tertiary Care Hospital of Punjab, India.
AB  - We determined the prevalence and antibiotic susceptibilities patterns of
      bacterial isolates from pus samples collected from patients in a tertiary care
      hospital of Punjab, India. E. coli was the most prevalent pathogen (51.2%)
      followed by Staphylococcus aureus (21%), Klebsiella pneumoniae (11.6%),
      Pseudomonas aeruginosa (5.8%), Citrobacter spp. (3.5%), Acinetobacter baumannii
      (2.3%), Proteus mirabilis (2.3%), and Streptococcus spp. (2.3%). E. coli, K.
      pneumoniae, A. baumannii, and Citrobacter isolates were resistant to multiple
      antibiotics including higher generation cephalosporins. S. aureus and
      Streptococcus isolates were sensitive to cloxacillin and vancomycin. However, P.
      aeruginosa, P. mirabilis, and Streptococcus isolates were found to be less
      resistant to the spectrum of antibiotics tested. Overall, our findings indicate
      the prevalence of resistance to different classes of antibiotics in bacterial
      isolates from pus infections and hence highlight the need for effective
      surveillance, regulator reporting, and antibiogram-guided antibiotic
      prescription.

PMID- 27872644
TI  - Rosai-Dorfman Disease Involving Multiple Organs: An Unusual Case with Poor
      Prognosis.
AB  - Rosai-Dorfman disease is a rare, benign histiocytic proliferative disorder that
      usually affects the lymph nodes. Although extranodal involvement has been
      reported in diverse sites, manifestation in the cardiovascular system is
      extremely rare. Specifically, cardiac involvement in Rosai-Dorfman disease is an
      extraordinarily infrequent event. We describe a case of a 36-year-old female who
      presented Rosai-Dorfman disease of multiple organs including the heart, with poor
      prognosis.

PMID- 27872645
TI  - Traumatic Lung Herniation following Skateboard Fall.
AB  - Lung herniation (LH) is a rare clinical entity involving the protrusion of lung
      outside the thoracic cage. It has a variety of etiologies and clinical
      presentations, making diagnosis difficult. We present a case of a 20-year-old
      male who reported pleuritic pain after falling from a skateboard. Evaluation
      through computed tomography (CT) scanning of the chest revealed an anterior lung
      hernia associated with rib fractures. This case emphasizes the need for
      clinicians to include lung herniation in the differential diagnosis of patients
      with trauma and inexplicable or persistent pulmonary issues.

PMID- 27872646
TI  - Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as
      Neurochemical Markers of Accidental Intoxication.
AB  - Introduction. Chronic poisoning may result in home setting after mercury (Hg)
      vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg
      poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72
      year-old man with polyneuropathy of suspected toxic origin. At hospitalization,
      toxicological clinical evaluations confirmed the altered neurological picture
      documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg)
      monitoring were performed from admission (t0), until 1 year later (t2),
      paralleled by blood neurochemical markers assessment, that is, lymphocytes
      muscarinic receptors (l-MRs). At t0: BHg and UHg were 27 and 1.4 microg/L,
      respectively (normal values: BHg 1-4.5; UHg 0.1-4.5), associated with l-MRs
      increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0-16.0). At t1
      (two days after DMSA-mobilization test), BHg weak reduction, paralleled by UHg
      3.7-fold increase, was measured together with further l-MRs enhancement (205.43
      femtomoL/million lymphocytes). At t2 (eight months after two cycles of DMSA
      chelating therapy ending), gradual improving of clinical manifestations was
      accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp.)
      and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes).
      Conclusion. l-MRs modulatory effect supports their use as peripheral
      neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.

PMID- 27872648
TI  - A 58-Year-Old Female with Progressive Cough and Right Shoulder Pain.
AB  - Cavitary pneumonia in immunocompromised patients is a challenging entity.
      Establishing accurate diagnosis and starting effective antibiotics are essential
      steps towards improving outcome. A 58-year-old stem cell transplant patient was
      admitted to the hospital with necrotizing pneumonia caused by nocardia. The
      disease progressed despite of aggrieve antimicrobial therapy. Nocardiosis
      continues to be a difficult disease to diagnose and treat.

PMID- 27872649
TI  - A Green Antioxidant Activity-Integrated Dual-Standard Method for Rapid Evaluation
      of the Quality of Traditional Chinese Medicine Xuebijing Injection by On-Line
      DPPH-CE-DAD.
AB  - Much attention has been focused on treatment of sepsis which leads to high
      mortality all over the world in every year. Antioxidant activity seems to play a
      prominent role in the treatment of sepsis exhibited by Xuebijing injection. The
      aim of the present research was to develop an on-line 1, 1-diphenyl-2
      picrylhydrazyl- (DPPH-) capillary electrophoresis-diode array detector (on-line
      DPPH-CE-DAD) method for rapidly assessing antioxidant properties and efficacious
      material basis of antioxidant activity as a way of quality control of Xuebijing
      injection. Several parameters affecting the separation were investigated,
      including the pH and concentrations of buffer, SDS, beta-CD, and organic modifier
      as well as voltage and cassette temperature. Compared to previous traditional
      method, this improved method shortened the experimental cycle and became more
      efficient because it was successfully applied to analyze total antioxidant
      activity and contents of twelve antioxidants of Xuebijing injection under the
      same condition. The results revealed that the on-line DPPH-CE-DAD method was a
      reagent-saving, rapid, feasible, and green technique for quality control of
      Xuebijing injection in terms of pharmacological activity and contents of active
      ingredients. It also offered new opportunities for the analysis of antioxidant
      activity of complex matrix.

PMID- 27872647
TI  - Antimalarial Properties of Aqueous Crude Extracts of Gynostemma pentaphyllum and
      Moringa oleifera Leaves in Combination with Artesunate in Plasmodium berghei
      Infected Mice.
AB  - Due to the emergence and spread of malaria parasite with resistance to
      antimalarial drugs, discovery and development of new, safe, and affordable
      antimalarial are urgently needed. In this respect, medicinal plant extracts are
      targets to optimize antimalarial actions and restore efficacy of standard
      antimalarial drugs. The present study was aimed at determining the antimalarial
      activities of Gynostemma pentaphyllum and Moringa oleifera leaf extracts in
      combination with artesunate against Plasmodium berghei-infected mice. P. berghei
      ANKA maintained by serial passage in ICR mice were used based on intraperitoneal
      injection of 1 * 107 parasitized erythrocytes and subsequent development of
      parasitemia. These infected mice were used to investigate the antimalarial
      activity of artesunate (6 mg/kg) in combination with 500, 1,000, and 2,000 mg/kg
      of G. pentaphyllum and M. oleifera leaf extracts using 4-day suppressive test. It
      was found that these extracts showed significant (P < 0.05) antimalarial activity
      in dose-dependent manner with percentage of suppression of 45, 50, and 55% for G.
      pentaphyllum leaf extract and 35, 40, and 50% for M. oleifera leaf extract.
      Additionally, artesunate combined with these extracts presented higher
      antimalarial activity, compared to extract treated alone with percentage of
      suppression of 78, 91, and 96% for G. pentaphyllum leaf extract and 73, 82, and
      91% for M. oleifera leaf extract. The results indicated that combination
      treatment of G. pentaphyllum or M. oleifera leaf extracts with artesunate was
      able to increase the antimalarial activity by using low dose of artesunate.
      Hence, these results justified the combination of these extracts and artesunate
      in antimalarial herbal remedies.

PMID- 27872650
TI  - The Cholesterol-Lowering Effect of Alisol Acetates Based on HMG-CoA Reductase and
      Its Molecular Mechanism.
AB  - This study measured the impact of alisol B 23-acetate and alisol A 24-acetate,
      the main active ingredients of the traditional Chinese medicine Alismatis
      rhizoma, on total cholesterol (TC), triglyceride (TG), high density lipoprotein
      cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) levels of
      hyperlipidemic mice. The binding of alisol B 23-acetate and alisol A 24-acetate
      to the key enzyme involved in the metabolism of TC, 3-hydroxy-3-methylglutary
      coenzyme A (HMG-CoA) reductase, was studied using the reagent kit method and the
      western blotting technique combined with a molecular simulation technique.
      According to the results, alisol acetates significantly lower the TC, TG, and LDL
      C concentrations of hyperlipidemic mice, while raising HDL-C concentrations.
      Alisol acetates lower HMG-CoA reductase activity in a dose-dependent fashion,
      both in vivo and in vitro. Neither of these alisol acetates significantly lower
      the protein expression of HMG-CoA. This suggests that alisol acetates lower the
      TC level via inhibiting the activity of HMG-CoA reductase by its prototype drug,
      which may exhibit an inhibition effect via directly and competitively binding to
      HMG-CoA. The side chain of the alisol acetate was the steering group via
      molecular simulation.

PMID- 27872652
TI  - Corrigendum to "Effects of an Aqueous Extract of Dangguijagyagsan on Serum Lipid
      Levels and Blood Flow Improvement in Ovariectomized Rats".
AB  - [This corrects the article DOI: 10.1155/2014/497836.].

PMID- 27872651
TI  - A Review of Western and Traditional Chinese Medical Approaches to Managing
      Nonalcoholic Fatty Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a disease of attention because of
      increase in prevalence from 20% to 41%. The clinical and pathological conditions
      in patients with NAFLD range from steatosis alone to nonalcoholic steatohepatitis
      (NASH) with or without fibrosis to hepatic cancer. In the United States, NAFLD
      was the second-leading indication for liver transplant between 2004 and 2013.
      Although imaging studies such as magnetic resonance elastography and the use of
      diagnostic panels and scoring systems can provide a fairly accurate diagnosis of
      NAFLD, there are few treatment options for patients with mild to moderate disease
      other than lifestyle modification. Many of the currently used medical treatments
      have been shown to cause severe side effects and some have been shown to be
      associated with increased risk for certain types of cancer. In recent years, a
      number of traditional Chinese herbal treatments have been examined for their
      potential uses as treatment for NAFLD. In this review, we provide a general
      overview of NAFLD and a survey of Western pharmacologic drugs currently used to
      treat the disease as well as the results of recent studies on the effectiveness
      of traditional Chinese herbal remedies for managing nonalcoholic fatty liver
      disease.

PMID- 27872653
TI  - The Zuo Jin Wan Formula Induces Mitochondrial Apoptosis of Cisplatin-Resistant
      Gastric Cancer Cells via Cofilin-1.
AB  - Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in
      the treatment of cancer, the development of multidrug resistance often leads to a
      failure of DDP therapy. Here we found that phosphorylated cofilin-1 (p-cofilin-1)
      was overexpressed in the DDP-resistant human gastric cancer cell lines
      SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines (SGC7901
      and BGC823), and that DDP induced the dephosphorylation of p-cofilin-1 in both
      parent lines but not in the DDP-resistant lines. However, we noted that the
      traditional Chinese medicine formula Zuo Jin Wan (ZJW) could induce the
      dephosphorylation of p-cofilin-1 and promote cofilin-1 translocation from the
      cytoplasm into the mitochondria in both SGC7901/DDP and BGC823/DDP cells. This
      mitochondrial translocation of cofilin-1 was found to induce the conversion of
      filamentous actin to globular-actin, activate mitochondrial damage and calcium
      overloading, and induce the mitochondrial apoptosis pathway. We further observed
      that these effects of ZJW on DDP-resistant human gastric cancer cell lines could
      be reversed via transfection with cofilin-1-specific siRNA, or treatment with a
      PP1 and PP2A inhibitor. These results suggest that ZJW is an effective drug
      therapy for patients with DDP-resistant gastric cancer.

PMID- 27872654
TI  - Chlorophyll a fluorescence, under half of the adaptive growth-irradiance, for
      high-throughput sensing of leaf-water deficit in Arabidopsis thaliana accessions.
AB  - BACKGROUND: Non-invasive and high-throughput monitoring of drought in plants from
      its initiation to visible symptoms is essential to quest drought tolerant
      varieties. Among the existing methods, chlorophyll a fluorescence (ChlF) imaging
      has the potential to probe systematic changes in photosynthetic reactions;
      however, prerequisite of dark-adaptation limits its use for high-throughput
      screening. RESULTS: To improve the throughput monitoring of plants, we have
      exploited their light-adaptive strategy, and investigated possibilities of
      measuring ChlF transients under low ambient irradiance. We found that the ChlF
      transients and associated parameters of two contrasting Arabidopsis thaliana
      accessions, Rsch and Co, give almost similar information, when measured either
      after ~20 min dark-adaptation or in the presence of half of the adaptive growth
      irradiance. The fluorescence parameters, effective quantum yield of PSII
      photochemistry (PhiPSII) and fluorescence decrease ratio (RFD) resulting from
      this approach enabled us to differentiate accessions that is often not possible
      by well-established dark-adapted fluorescence parameter maximum quantum
      efficiency of PSII photochemistry (FV/FM). Further, we screened ChlF transients
      in rosettes of well-watered and drought-stressed six A. thaliana accessions,
      under half of the adaptive growth-irradiance, without any prior dark-adaptation.
      Relative water content (RWC) in leaves was also assayed and compared to the ChlF
      parameters. As expected, the RWC was significantly different in drought-stressed
      from that in well-watered plants in all the six investigated accessions on day-10
      of induced drought; the maximum reduction in the RWC was obtained for Rsch (16%),
      whereas the minimum reduction was for Co (~7%). Drought induced changes were
      reflected in several features of ChlF transients; combinatorial images obtained
      from pattern recognition algorithms, trained on pixels of image sequence,
      improved the contrast among drought-stressed accessions, and the derived images
      were well-correlated with their RWC. CONCLUSIONS: We demonstrate here that ChlF
      transients and associated parameters measured even in the presence of low ambient
      irradiance preserved its features comparable to that of measured after dark
      adaptation and discriminated the accessions having differential geographical
      origin; further, in combination with combinatorial image analysis tools, these
      data may be readily employed for early sensing and mapping effects of drought on
      plant's physiology via easy and fully non-invasive means.

PMID- 27872655
TI  - Novel Burst Suppression Segmentation in the Joint Time-Frequency Domain for EEG
      in Treatment of Status Epilepticus.
AB  - We developed a method to distinguish bursts and suppressions for EEG burst
      suppression from the treatments of status epilepticus, employing the joint time
      frequency domain. We obtained the feature used in the proposed method from the
      joint use of the time and frequency domains, and we estimated the decision as to
      whether the measured EEG was a burst segment or suppression segment by the
      maximum likelihood estimation. We evaluated the performance of the proposed
      method in terms of its accordance with the visual scores and estimation of the
      burst suppression ratio. The accuracy was higher than the sole use of the time or
      frequency domains, as well as conventional methods conducted in the time domain.
      In addition, probabilistic modeling provided a more simplified optimization than
      conventional methods. Burst suppression quantification necessitated precise burst
      suppression segmentation with an easy optimization; therefore, the excellent
      discrimination and the easy optimization of burst suppression by the proposed
      method appear to be beneficial.

PMID- 27872656
TI  - Nutritional situation among Syrian refugees hosted in Iraq, Jordan, and Lebanon:
      cross sectional surveys.
AB  - BACKGROUND: Ongoing armed conflict in Syria has caused large scale displacement.
      Approximately half of the population of Syria have been displaced including the
      millions living as refugees in neighboring countries. We sought to assess the
      health and nutrition of Syrian refugees affected by the conflict. METHODS:
      Representative cross-sectional surveys of Syrian refugees were conducted between
      October 2 and November 30, 2013 in Lebanon, April 12 and May 1, 2014 in Jordan,
      and May 20 and 31, 2013 in Iraq. Surveys in Lebanon were organized in four
      geographical regions (North, South, Beirut/Mount Lebanon and Bekaa). In Jordan,
      independent surveys assessed refugees residing in Za'atri refugee camp and
      refugees residing among host community nationwide. In Iraq, refugees residing in
      Domiz refugee camp in the Kurdistan region were assessed. Data collected on
      children aged 6 to 59 months included anthropometric indicators, morbidity and
      feeding practices. In Jordan and Lebanon, data collection also included
      hemoglobin concentration for children and non-pregnant women aged 15 to 49 years,
      anthropometric indicators for both pregnant and non-pregnant women, and household
      level indicators such as access to safe water and sanitation. RESULTS: The
      prevalence of global acute malnutrition among children 6 to 59 months of age was
      less than 5 % in all samples (range 0.3-4.4 %). Prevalence of acute malnutrition
      among women 15 to 49 years of age, defined as mid-upper arm circumference less
      than 23.0 cm, was also relatively low in all surveys (range 3.5-6.5 %). For both
      children and non-pregnant women, anemia prevalence was highest in Za'atri camp in
      Jordan (48.4 % and 44.8 %, respectively). Most anemia was mild or moderate;
      prevalence of severe anemia was less than or equal to 1.1 % in all samples of
      children and women. CONCLUSIONS: Despite the ongoing conflict, results from all
      surveys indicate that global acute malnutrition is relatively low in the assessed
      Syrian refugee populations. However, prevalence of anemia suggests a serious
      public health problem among women and children, especially in Za'atri camp. Based
      on these findings, nutrition partners in the region have reprioritized response
      interventions, focusing on activities to address micronutrient deficiencies such
      as food fortification.

PMID- 27872657
TI  - A pilot test of the acceptability and efficacy of narrative and non-narrative
      health education materials in a low health literacy population.
AB  - Although entertainment-education narratives are increasingly being used to
      communicate health information to a diversity of populations, there is limited
      evidence examining the use of narrative health education videos in low compared
      with adequate health literacy populations. There are also very few studies
      directly comparing narrative materials to more traditional, non-narrative
      materials. Because individuals with low health literacy are less likely than
      those with adequate health literacy to benefit from health communication
      interventions, it is especially important to develop an evidence base supporting
      the use of narrative health education materials in low literacy populations. This
      study extends knowledge on the use of narrative health education materials in
      populations with low health literacy by conducting a randomized trial comparing
      the acceptability and efficacy (knowledge gain) of two fact-equivalent films, one
      in a narrative and one in a non-narrative format, on individuals with adequate
      and low health literacy. This study finds that while both films were well
      accepted and produced knowledge gains, the narrative film was more effective in
      this regard. This effect occurred regardless of health literacy level, indicating
      that narrative health communication materials are appropriate for individuals
      with low health literacy and do not exacerbate existing health disparities. These
      findings add to a small but growing body of evidence testing narrative health
      education materials in individuals with low health literacy, and provide new
      evidence supporting narrative, entertainment-education style video as a health
      communication tool to help reduce health literacy-related health disparities.

PMID- 27872658
TI  - Exploiting the dynamic properties of covalent modification cycle for the design
      of synthetic analog biomolecular circuitry.
AB  - BACKGROUND: Cycles of covalent modification are ubiquitous motifs in cellular
      signalling. Although such signalling cycles are implemented via a highly concise
      set of chemical reactions, they have been shown to be capable of producing
      multiple distinct input-output mapping behaviours - ultrasensitive, hyperbolic,
      signal-transducing and threshold-hyperbolic. RESULTS: In this paper, we show how
      the set of chemical reactions underlying covalent modification cycles can be
      exploited for the design of synthetic analog biomolecular circuitry. We show that
      biomolecular circuits based on the dynamics of covalent modification cycles allow
      (a) the computation of nonlinear operators using far fewer chemical reactions
      than purely abstract designs based on chemical reaction network theory, and (b)
      the design of nonlinear feedback controllers with strong performance and
      robustness properties. CONCLUSIONS: Our designs provide a more efficient route
      for translation of complex circuits and systems from chemical reactions to DNA
      strand displacement-based chemistry, thus facilitating their experimental
      implementation in future Synthetic Biology applications.

PMID- 27872660
TI  - Improvement of catalytic performance of lignin peroxidase for the enhanced
      degradation of lignocellulose biomass based on the imbedded electron-relay in
      long-range electron transfer route.
AB  - BACKGROUND: Although lignin peroxidase is claimed as a key enzyme in enzyme
      catalyzed lignin degradation, in vitro enzymatic degradation of lignin was not
      easily observed in lab-scale experiments. It implies that other factors may
      hinder the enzymatic degradation of lignin. Irreversible interaction between
      phenolic compound and lignin peroxidase was hypothesized when active enzyme could
      not be recovered after the reaction with degradation product (guaiacol) of lignin
      phenolic dimer. RESULTS: In the study of lignin peroxidase isozyme H8 from white
      rot fungi Phanerochaete chrysosporium (LiPH8), W251 site was revealed to make the
      covalent coupling with one moiety of monolignolic radical (guaiacol radical) by
      LC-MS/MS analysis. Hypothetical electron-relay containing W251 residue was newly
      suggested based on the observation of repressed radical coupling and remarkably
      lower electron transfer rate for W215A mutant. Furthermore, the retardation of
      the suicidal radical coupling between the W251 residue and the monolignolic
      radical was attempted by supplementing the acidic microenvironment around the
      W251 residue to engineer radical-robust LiPH8. Among many mutants, mutant A242D
      showed exceptional catalytic performances by yielding 21.1- and 4.9-fold higher
      increases of kcat and kcat/KM values, respectively, in the oxidation of non
      phenolic model lignin dimer. CONCLUSIONS: A mechanism-based suicide inhibition of
      LiPH8 by phenolic compounds was firstly revealed and investigated in this work.
      Radical-robust LiPH8 was also successfully engineered by manipulating the
      transient radical state of radical-susceptible electron-relay. Radical-robust
      LiPH8 will play an essential role in degradation of lignin, which will be
      consequently linked with improved production of sugars from lignocellulose
      biomass.

PMID- 27872661
TI  - Production of l(+)-lactic acid from acid pretreated sugarcane bagasse using
      Bacillus coagulans DSM2314 in a simultaneous saccharification and fermentation
      strategy.
AB  - BACKGROUND: Sugars derived from lignocellulose-rich sugarcane bagasse can be used
      as feedstock for production of l(+)-lactic acid, a precursor for renewable
      bioplastics. In our research, acid-pretreated bagasse was hydrolysed with the
      enzyme cocktail GC220 and fermented by the moderate thermophilic bacterium
      Bacillus coagulans DSM2314. Saccharification and fermentation were performed
      simultaneously (SSF), adding acid-pretreated bagasse either in one batch or in
      two stages. SSF was performed at low enzyme dosages of 10.5-15.8 FPU/g DW
      bagasse. RESULTS: The first batch SSF resulted in an average productivity of 0.78
      g/l/h, which is not sufficient to compete with lactic acid production processes
      using high-grade sugars. Addition of 1 g/l furfural to precultures can increase
      B. coagulans resistance towards by-products present in pretreated lignocellulose.
      Using furfural-containing precultures, productivity increased to 0.92 g/l/h, with
      a total lactic acid production of 91.7 g in a 1-l reactor containing 20% W/W DW
      bagasse. To increase sugar concentrations, bagasse was solubilized with a liquid
      fraction, obtained directly after acid pretreatment. Solubilizing the bagasse
      fibres with water increased the average productivity to 1.14 g/l/h, with a total
      lactic acid production of 84.2 g in a 1-l reactor. Addition of bagasse in two
      stages reduced viscosity during SSF, resulting in an average productivity in the
      first 23 h of 2.54 g/l/h, similar to productivities obtained in fermentations
      using high-grade sugars. Due to fast accumulation of lactic acid, enzyme activity
      was repressed during two-stage SSF, resulting in a decrease in productivity and a
      slightly lower total lactic acid production of 75.6 g. CONCLUSIONS: In this
      study, it is shown that an adequate production of lactic acid from lignocellulose
      was successfully accomplished by a two-stage SSF process, which combines acid
      pretreated bagasse, B. coagulans precultivated in the presence of furfural as
      microorganism, and GC220 as enzyme cocktail. The process may be further improved
      by enhancing enzyme hydrolysis activities at high lactic acid concentrations.

PMID- 27872659
TI  - Whole-genome de novo sequencing, combined with RNA-Seq analysis, reveals unique
      genome and physiological features of the amylolytic yeast Saccharomycopsis
      fibuligera and its interspecies hybrid.
AB  - BACKGROUND: Genomic studies on fungal species with hydrolytic activity have
      gained increased attention due to their great biotechnological potential for
      biomass-based biofuel production. The amylolytic yeast Saccharomycopsis
      fibuligera has served as a good source of enzymes and genes involved in
      saccharification. Despite its long history of use in food fermentation and
      bioethanol production, very little is known about the basic physiology and
      genomic features of S. fibuligera. RESULTS: We performed whole-genome (WG) de
      novo sequencing and complete assembly of S. fibuligera KJJ81 and KPH12, two
      isolates from wheat-based Nuruk in Korea. Intriguingly, the KJJ81 genome (~38 Mb)
      was revealed as a hybrid between the KPH12 genome (~18 Mb) and another
      unidentified genome sharing 88.1% nucleotide identity with the KPH12 genome. The
      seven chromosome pairs of KJJ81 subgenomes exhibit highly conserved synteny,
      indicating a very recent hybridization event. The phylogeny inferred from WG
      comparisons showed an early divergence of S. fibuligera before the separation of
      the CTG and Saccharomycetaceae clades in the subphylum Saccharomycotina.
      Reconstructed carbon and sulfur metabolic pathways, coupled with RNA-Seq
      analysis, suggested a marginal Crabtree effect under high glucose and activation
      of sulfur metabolism toward methionine biosynthesis under sulfur limitation in
      this yeast. Notably, the lack of sulfate assimilation genes in the S. fibuligera
      genome reflects a unique phenotype for Saccharomycopsis clades as natural sulfur
      auxotrophs. Extended gene families, including novel genes involved in
      saccharification and proteolysis, were identified. Moreover, comparative genome
      analysis of S. fibuligera ATCC 36309, an isolate from chalky rye bread in
      Germany, revealed that an interchromosomal translocation occurred in the KPH12
      genome before the generation of the KJJ81 hybrid genome. CONCLUSIONS: The
      completely sequenced S. fibuligera genome with high-quality annotation and RNA
      Seq analysis establishes an important foundation for functional inference of S.
      fibuligera in the degradation of fermentation mash. The gene inventory
      facilitates the discovery of new genes applicable to the production of novel
      valuable enzymes and chemicals. Moreover, as the first gapless genome assembly in
      the genus Saccharomycopsis including members with desirable traits for
      bioconversion, the unique genomic features of S. fibuligera and its hybrid will
      provide in-depth insights into fungal genome dynamics as evolutionary adaptation.

PMID- 27872663
TI  - From the Collective Unconscious to the Narrative Unconscious: Re-Imagining the
      Sources of Selfhood.

PMID- 27872662
TI  - Similar compounds versus similar conformers: complementarity between PubChem 2-D
      and 3-D neighboring sets.
AB  - BACKGROUND: PubChem is a public repository for biological activities of small
      molecules. For the efficient use of its vast amount of chemical information,
      PubChem performs 2-dimensional (2-D) and 3-dimensional (3-D) neighborings, which
      precompute "neighbor" relationships between molecules in the PubChem Compound
      database, using the PubChem subgraph fingerprints-based 2-D similarity and the
      Gaussian-shape overlay-based 3-D similarity, respectively. These neighborings
      allow PubChem to provide the user with immediate access to the list of 2-D and 3
      D neighbors (also called "Similar Compounds" and "Similar Conformers",
      respectively) for each compound in PubChem. However, because 3-D neighboring is
      much more time-consuming than 2-D neighboring, how different the results of the
      two neighboring schemes are is an important question, considering limited
      computational resources. RESULTS: The present study analyzed the complementarity
      between the PubChem 2-D and 3-D neighbors. When all compounds in PubChem were
      considered, the overlap between 2-D and 3-D neighbors was only 2% of the total
      neighbors. For the data sets containing compounds with annotated information, the
      overlap increased as the data sets became smaller. However, it did not exceed 31%
      and substantial fractions of neighbors were still recognized by either PubChem 2
      D or 3-D similarity, but not by both. The Neighbor Preference Index (NPI) of a
      molecule for a given data set was introduced, which quantified whether a molecule
      had more 2-D or 3-D neighbors in the data set. The NPI histogram for all PubChem
      compounds had a bimodal shape with two maxima at NPI = +/-1 and a minimum at NPI
      = 0. However, the NPI histograms for the subsets containing compounds with
      annotated information had a greater fraction of compounds with a strong
      preference for one neighboring method to the other (at NPI = +/-1) as well as
      compounds with a neutral preference (at NPI = 0). CONCLUSION: The results of our
      study indicate that, for the majority of the compounds in PubChem, their
      structural similarity to other compounds can be recognized predominantly by
      either 2-D or 3-D neighborings, but not by both, showing a strong complementarity
      between 2-D and 3-D neighboring results. Therefore, despite its heavy
      requirements for computational resources, 3-D neighboring provides an alternative
      way in which the user can instantly access structurally similar molecules that
      cannot be detected if only 2-D neighboring is used.Graphical AbstractThe binned
      distribution of the neighbor preference indices (NPIs) for all compounds in
      PubChem (left) has a bimodal shape with two maxima at NPI = +/-1 and a minimum at
      NPI = 0, indicating that structural similarity between compounds in PubChem can
      be recognized predominantly by either 2-D or 3-D neighborings, but not by both.
      The NPI histogram for the drug space (right) has a greater fraction of compounds
      with a strong preference for one neighboring method to the other (at NPI ~ +/-1)
      as well as compounds with a neutral preference (at NPI ~ 0), indicating that the
      drug space is very different from the PubChem space.

PMID- 27872664
TI  - General and Domain-Specific Contributions to Creative Ideation and Creative
      Performance.
AB  - The general objective of this study was to reexamine two views of creativity, one
      positing that there is a general creative capacity or talent and the other that
      creativity is domain-specific. These two views were compared by (a) testing
      correlations among measures of domain-general and domain-specific creativity and
      (b) examining how the general and the specific measures was each related to
      indices of knowledge, motivation, and personality. Participants were 147 college
      students enrolled in a foreign language course. Data were collected on
      participants' domain knowledge, motivation, and creative personality, as well as
      four measures representing "General or Domain-Specific Creative Ideation" or
      "Creative Performance and Activity". Results indicated that the four measures of
      creativity were correlated with one another, except for "General Performance and
      Activity" and "Domain-Specific Ideation." A canonical correlation indicated that
      knowledge, motivation, and personality were significantly correlated with the
      four creativity measures (Rc = .49, p < .01). Multiple regressions uncovered
      particular relationships consistent with the view that creativity has both
      general and domain-specific contributions. Limitations, such as the focus on one
      domain, and future directions are discussed.

PMID- 27872665
TI  - If Stigmatized, Self-Esteem Is not Enough: Effects of Sexism, Self-Esteem and
      Social Identity on Leadership Aspiration.
AB  - Ambivalent sexism has many pernicious consequences. Since gender stereotypes also
      affect leadership roles, the present research investigated the effects of
      ambivalent sexism on envisioning oneself as a leader. Our studies tested the
      influence of sexist attitudes (toward women - Study 1 - and men - Study 2) on
      leadership aspiration, taking into account the interaction among ambivalent
      attitudes, personal characteristics (e.g. self-esteem), and group processes (e.g.
      level of identification with gender). Specifically, the current study used a 3
      (sexism: hostile, benevolent, control) x 2 (social identification: high, low) x 2
      (self-esteem: high, low) factorial design. 178 women participated in Study 1.
      Results showed that, although sexism was not recognised as a form of prejudice
      and did not trigger negative emotions, in sexist conditions high-identified women
      increase their leadership aspiration. In Study 2 men (N = 184) showed to
      recognise hostility as a form of prejudice, to experience more negative emotions,
      but to be not influenced in leadership aspiration. For both men and women self
      esteem had a significant main effect on leadership aspiration.

PMID- 27872666
TI  - Fifty Shades of Unsaid: Women's Explicit and Implicit Attitudes Towards Sexual
      Morality.
AB  - The movie Fifty Shades of Grey has created a great deal of controversy which has
      reignited the debate on unusual and alternative sexual practices such as bondage.
      Erotophobic individuals have negative affect towards the type of sexual
      libertinism conveyed by the movie, while erotophilic persons have a positive
      attitude and emotional feelings towards this kind of sexual emancipation. Using
      the Implicit Association Test, this study aimed to explore the extent to which
      there is a difference in women's attitudes towards sexual morality on an explicit
      and implicit level. Our findings found that erotophobic and erotophilic women
      differed only on an explicit level of sex guilt and moral evaluation, while no
      difference in the implicit measure was found.

PMID- 27872667
TI  - The Relationship Between Accuracy of Numerical Magnitude Comparisons and
      Children's Arithmetic Ability: A Study in Iranian Primary School Children.
AB  - The relationship between children's accuracy during numerical magnitude
      comparisons and arithmetic ability has been investigated by many researchers.
      Contradictory results have been reported from these studies due to the use of
      many different tasks and indices to determine the accuracy of numerical magnitude
      comparisons. In the light of this inconsistency among measurement techniques, the
      present study aimed to investigate this relationship among Iranian second grade
      children (n = 113) using a pre-established test (known as the Numeracy Screener)
      to measure numerical magnitude comparison accuracy. The results revealed that
      both the symbolic and non-symbolic items of the Numeracy Screener significantly
      correlated with arithmetic ability. However, after controlling for the effect of
      working memory, processing speed, and long-term memory, only performance on
      symbolic items accounted for the unique variances in children's arithmetic
      ability. Furthermore, while working memory uniquely contributed to arithmetic
      ability in one-and two-digit arithmetic problem solving, processing speed
      uniquely explained only the variance in single-digit arithmetic skills and long
      term memory did not contribute to any significant additional variance for one
      digit or two-digit arithmetic problem solving.

PMID- 27872668
TI  - With a Little Help From My Family: A Mixed-Method Study on the Outcomes of Family
      Support and Workload.
AB  - Our aim was to investigate some predictors and outcomes of family-to-work
      enrichment (FWE) via a mixed-method approach. We sampled 447 married employees of
      an Italian factory. Survey results from Study 1 showed that emotional support
      from family positively predicted FWE, while this latter mediated the associations
      between the former on one side, and work engagement and life satisfaction on the
      other. Moreover, extra-household support directly associated positively with life
      satisfaction. Evidence from 20 anthropological in-depth interviews (Study 2)
      returned a more complex picture, highlighting the gendered role of partners
      inside couples, the importance of kinship support, the sense and the value of
      filiation and parenthood in their connection with job roles, the complex and
      continuous interplay between family and life domains. In combination, results
      from both studies stressed the importance of family support; additionally,
      evidences from Study 2 suggested that FWE could be better understood taking into
      account crossover dynamics and the compresence of work-to-family enrichment and
      conflict. In sum, these studies contributed to shed light on FWE dynamics, an
      under-researched topic in Italy, whose knowledge could be of great empirical and
      practical value.

PMID- 27872669
TI  - Mothers and Fathers in NICU: The Impact of Preterm Birth on Parental Distress.
AB  - Preterm birth is a stressful event for families. In particular, the unexpectedly
      early delivery may cause negative feelings in mothers and fathers. The aim of
      this study was to examine the relationship between preterm birth, parental stress
      and negative feelings, and the environmental setting of NICU. 21 mothers (age =
      36.00 +/- 6.85) and 19 fathers (age = 34.92 +/- 4.58) of preterm infants (GA =
      30.96 +/- 2.97) and 20 mothers (age = 40.08 +/- 4.76) and 20 fathers (age = 40.32
      +/- 6.77) of full-term infants (GA = 39.19 +/- 1.42) were involved. All parents
      filled out the Parental Stressor Scale: Neonatal Intensive Care Unit, the Impact
      of Event Scale Revised, Profile of Mood States, the Multidimensional Scale of
      Perceived Social Support and the Post-Partum Bonding Questionnaire. Our data
      showed differences in emotional reactions between preterm and full-term parents.
      Results also revealed significant differences between mothers and fathers'
      responses to preterm birth in terms of stress, negative feelings, and perceptions
      of social support. A correlation between negative conditions at birth (e.g.,
      birth weight and Neonatal Intensive Care Unit stay) and higher scores in some
      scales of Impact of Event Scale Revised, Profile of Mood States and Post-Partum
      Bonding Questionnaire were found. Neonatal Intensive Care Unit may be a stressful
      place both for mothers and fathers. It might be useful to plan, as soon as
      possible, interventions to help parents through the experience of the premature
      birth of their child and to begin an immediately adaptive mode of care.

PMID- 27872671
TI  - Effects of Religious Priming Concepts on Prosocial Behavior Towards Ingroup and
      Outgroup.
AB  - Several studies show that there is a connection between religion and prosociality
      (e.g., Saroglou, 2013). To investigate whether there is a causal relationship
      between these two variables, a growing number of scholars employed priming
      religious concepts and measure its influence on prosocial behavior (e.g., Pichon,
      Boccato, & Saroglou, 2007). In the recent development of religious priming,
      Ritter and Preston (2013) argued that different primes (agent prime,
      spiritual/abstract prime, and institutional prime) may also have varying
      influence on prosocial behavior specifically helping an ingroup or an outgroup
      target. With this in mind, a 2 (social categorization of the target of help) by 3
      (agent prime, institutional prime, spiritual prime) experiment was conducted to
      directly investigate this hypothesis. Results suggest that priming religious
      concepts especially the spiritual prime can increase prosocial behaviors.
      However, no significant effect was found on the social categorization which
      implies that Filipino participants elicit prosocial behavior regardless of the
      social categorization (be it ingroup or outgroup) of the target of help. The
      present study's findings contribute to further the literature on religious
      priming and its influence on prosocial behavior.

PMID- 27872670
TI  - Meaning-Making Process Related to Temporality During Breast Cancer Traumatic
      Experience: The Clinical Use of Narrative to Promote a New Continuity of Life.
AB  - Previous research has agreed that meaning-making is a key element in the
      promotion of patients' well-being during and after a traumatic event such as
      cancer. In this paper, we focus on an underestimated key element related to the
      crisis/rupture of this meaning-making process with respect to the time
      perspective. We consider 40 narratives of breast cancer patients at different
      times of treatment, undergoing chemotherapy and biological therapy. We collected
      data through writing technique. We performed an interpretative thematic analysis
      of the data and highlighted specific ways to signify time during the different
      treatment phases. Our central aspect "the time of illness, the illness of time"
      demonstrates that the time consumed by illness has the risk of becoming an
      illness of time, which transcends the end of the illness and absorbs a patient's
      past, present, and future, thus saturating all space for thought and meaning. The
      study suggests that narrative can become a therapeutic and preventive tool for
      women with breast cancer in a crisis of temporality, and enable the promotion of
      new semiotic connections and a specific functional resynchronization with the
      continuity/discontinuity of life. This is useful during the illness and medical
      treatment and also after the treatment.

PMID- 27872672
TI  - Measuring the Effects of Self-Awareness: Construction of the Self-Awareness
      Outcomes Questionnaire.
AB  - Dispositional self-awareness is conceptualized in several different ways,
      including insight, reflection, rumination and mindfulness, with the latter in
      particular attracting extensive attention in recent research. While self
      awareness is generally associated with positive psychological well-being, these
      different conceptualizations are also each associated with a range of unique
      outcomes. This two part, mixed methods study aimed to advance understanding of
      dispositional self-awareness by developing a questionnaire to measure its
      outcomes. In Study 1, expert focus groups categorized and extended an initial
      pool of potential items from previous research. In Study 2, these items were
      reduced to a 38 item self-report questionnaire with four factors representing
      three beneficial outcomes (reflective self-development, acceptance and
      proactivity) and one negative outcome (costs). Regression of these outcomes
      against self-awareness measures revealed that self-reflection and insight
      predicted beneficial outcomes, rumination predicted reduced benefits and
      increased costs, and mindfulness predicted both increased proactivity and costs.
      These studies help to refine the self-awareness concept by identifying the unique
      outcomes associated with the concepts of self-reflection, insight, reflection,
      rumination and mindfulness. It can be used in future studies to evaluate and
      develop awareness-raising techniques to maximize self-awareness benefits while
      minimizing related costs.

PMID- 27872674
TI  - Cognition About the Creative Process - Interview With Dr Andrew P. Allen.
AB  - What is the relationship between the creative process and cognition and
      perception? Lynda Loughnane, a master's student in Art and Process in Crawford
      College of Art and Design, Cork, Ireland interviewed Dr Andrew P. Allen about the
      subject. Areas covered include mindfulness, Type 1 and Type 2 thinking, stage
      theories of creativity, engagement with the art process and the artwork,
      phenomenology and consciousness with and without self report. The interview was
      constructed to cover a wide range of subject matter, so as to gather as much
      information as possible in layman's language about the cognitive process in
      relation to creativity and interaction with art.

PMID- 27872673
TI  - The Relationship Between Neurocognitive Functioning and Occupational Functioning
      in Bipolar Disorder: A Literature Review.
AB  - Neurocognitive impairment in Bipolar Disorder (BD) has been widely reported, even
      during remission. Neurocognitive impairment has been identified as a contributing
      factor towards unfavourable psychosocial functioning within this population. The
      objective of this review was to investigate the association between
      neurocognitive impairment and occupational functioning in BD. A literature review
      of English-language journal articles from January 1990 to November 2013 was
      undertaken utilising the PsychINFO, Scopus and Web of Knowledge databases.
      Studies that made specific reference to occupational outcomes were included, and
      those that reported on global psychosocial measures were excluded. Majority of
      the papers reviewed (20 out of 23) identified an association between
      neurocognitive impairment (particularly in executive functioning, verbal learning
      and memory, processing speed and attention) and occupational functioning. Several
      methodological issues were identified. There was a discrepancy in the measures
      used to assess neurocognitive function across studies and also the definition and
      measurement of occupational functioning. The clinical features of the samples
      varied across studies, and confounding variables were intermittently controlled.
      The review focused on English-language papers only and hence there is a bias
      toward the Western labour market. These limitations therefore influence the
      generalizability of the interpreted findings and the reliability of comparisons
      across studies. Neurocognitive impairment in BD appears to play a role in
      occupational outcomes. The findings of this review highlight the challenges for
      future research in this area, particularly in the measurement of neurocognitive
      and occupational functioning. Incorporating neurocognitive interventions in the
      treatment of BD, which has traditionally focussed solely on symptomatic recovery,
      may advance the vocational rehabilitation of these patients.

PMID- 27872675
TI  - Erratum: "Humidity assay for studying plant-pathogen interactions in miniature
      controlled discrete humidity environments with good throughput" [Biomicrofluidics
      10, 034108 (2016)].
AB  - [This corrects the article DOI: 10.1063/1.4950998.].

PMID- 27872676
TI  - Progressive and self-limiting neurodegenerative disorders in Africa: a new
      prominent field of research led by South Africa but without strong health policy.
AB  - INTRODUCTION: Neurodegenerative disorders are involved in mortality and morbidity
      of every country. A high prevalence is estimated in Africa. Neurodegenerative
      disorders are defined by a progressive or self-limiting alteration of neurons
      implied in specific functional and anatomical functions. It encompasses a various
      range of clinical disorders from self-limiting to progressive. Focus on public
      health policies and scientific research is needed to understand the mechanisms to
      reduce this high prevalence. We use bibliometrics and mapping tools to explore
      the area studies and countries involved in scientific research on
      neurodegenerative disorders in Africa. METHODS: We used two databases: Web of
      Science and Pubmed. We analyzed the journals, most cited articles, authors,
      publication years, organizations, funding agencies, countries and keywords in Web
      of Science Core collection database and publication years and Medical Subject
      Headings in Pubmed database. We mapped the data using VOSviewer. RESULTS: We
      accessed 44 articles published between 1975 and 2014 in Web of Science Core
      collection Database and 669 from Pubmed database. The majority of which were
      after 2006. The main countries involved in research on neurodegenerative
      disorders in Africa the USA, the United Kingdom, France and South Africa
      representing the main network collaboration. Clinical neurology and Genetics
      hereditary are the main Web of Science categories whereas Neurosciences and
      Biochemistry and Molecular Biology are the main Web of Science categories for the
      general search "neurodegenerative disorders" not restrained to Africa. This is
      confirmed by Medical Subject Headings analysis from Pubmed with one more area
      study: Treatment. CONCLUSION: Neurodegenerative disorders research is leaded by
      South Africa with a network involving the USA, the UK, as well as African
      countries such Zambia. The chief field that emerged was on patient and hereditary
      as well as treatment. Public health policies were lacking fields in research
      whereas prevalence is estimated to be important in every country. New 17
      sustainable development goals of the United Nations could help in this way.

PMID- 27872677
TI  - [Erratum: predictors of success among first-year medical students at the
      university of Parakou].
AB  - [This corrects the article DOI: 10.11604/pamj.2016.23.87.8527.].

PMID- 27872678
TI  - Erratum: antithyroid drug induced agranulocytosis: what still we need to learn?
AB  - [This corrects the article DOI: 10.11604/pamj.2016.23.27.8365.].

PMID- 27872679
TI  - The Oxidative and Inflammatory State in Patients with Acute Renal Graft
      Dysfunction Treated with Tacrolimus.
AB  - Objective. To determine the oxidative stress/inflammation behavior in patients
      with/without acute graft dysfunction (AGD) with Tacrolimus. Methods. Cross
      sectional study, in renal transplant (RT) recipients (1-yr follow-up). Patients
      with AGD and without AGD were included. Serum IL-6, TNF-alpha, 8-isoprostanes (8
      IP), and Nitric Oxide (NO) were determined by ELISA; C-reactive protein (CRP) was
      determined by nephelometry; lipid peroxidation products (LPO) and superoxide
      dismutase (SOD) were determined by colorimetry. Results. The AGD presentation was
      at 5.09 +/- 3.07 versus 8.27 +/- 3.78 months (p < 0.001); CRP >3.19 mg/L was
      found in 21 versus 19 in the N-AGD group (p = 0.83); TNF-alpha 145.53 +/- 18.87
      pg/mL versus 125.54 +/- 15.92 pg/mL in N-AGD (p = 0.64); IL-6 2110.69 +/- 350.97
      pg/mL versus 1933.42 +/- 235.38 pg/mL in N-AGD (p = 0.13). The LPO were higher in
      AGD (p = 0.014): 4.10 +/- 0.69 uM versus 2.41 +/- 0.29 uM; also levels of 8-IP
      were higher in AGD 27.47 +/- 9.28 pg/mL versus 8.64 +/- 1.54 pg/mL (p = 0.01).
      Serum levels of NO in AGD were lower 138.44 +/- 19.20 umol/L versus 190.57 +/-
      22.04 umol/L in N-AGD (p = 0.042); antioxidant enzyme SOD activity was
      significantly diminished in AGD with 9.75 +/- 0.52 U/mL versus 11.69 +/- 0.55
      U/mL in N-AGD (p = 0.012). Discussion. Patients with RT present with a similar
      state of the proinflammatory cytokines whether or not they have AGD. The patients
      with AGD showed deregulation of the oxidative state with increased LPO and 8-IP
      and decreased NO and SOD.

PMID- 27872680
TI  - Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and
      Liver Dysfunction in Acute Kidney Injury.
AB  - Ischemia-reperfusion is a common cause for acute kidney injury and can lead to
      distant organ dysfunction. Glutathione is a major endogenous antioxidant and its
      depletion directly correlates to ischemia-reperfusion injury. The liver has high
      capacity for producing glutathione and is a key organ in modulating local and
      systemic redox balance. In the present study, we investigated the mechanism by
      which kidney ischemia-reperfusion led to glutathione depletion and oxidative
      stress. The left kidney of Sprague-Dawley rats was subjected to 45 min ischemia
      followed by 6 h reperfusion. Ischemia-reperfusion impaired kidney and liver
      function. This was accompanied by a decrease in glutathione levels in the liver
      and plasma and increased hepatic lipid peroxidation and plasma homocysteine
      levels. Ischemia-reperfusion caused a significant decrease in mRNA and protein
      levels of hepatic glutamate-cysteine ligase mediated through the inhibition of
      transcription factor Nrf2. Ischemia-reperfusion inhibited hepatic expression of
      cystathionine gamma-lyase, an enzyme responsible for producing cysteine (an
      essential precursor for glutathione synthesis) through the transsulfuration
      pathway. These results suggest that inhibition of glutamate-cysteine ligase
      expression and downregulation of the transsulfuration pathway lead to reduced
      hepatic glutathione biosynthesis and elevation of plasma homocysteine levels,
      which, in turn, may contribute to oxidative stress and distant organ injury
      during renal ischemia-reperfusion.

PMID- 27872682
TI  - Prophylactic liver transplantation for high-risk recurrent hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related
      death in the world. Radical treatment of HCC in early stages results in a long
      disease-free period and improved overall survival. The choice of optimal
      management strategy for HCC mainly depends on the severity of the underlying
      liver disease. For patients with decompensated liver cirrhosis and HCC within
      Milan criteria (MC), liver transplant (LT) is the choice of treatment. However,
      for patients with good residual liver reserve and HCC within MC, selection of
      other curative treatments such as liver resection (LR) or radiofrequency ablation
      may be a reasonable alternative. For patients without cirrhosis, LR can result in
      an overall survival similar to that provided by LT. Therefore, it is an accepted
      alternative to LT especially in areas with organ shortage. However, the
      cumulative 5-year recurrence rate of HCC post LR might be as high as 70%. For
      initial transplant-eligible (within MC) patients with recurrent HCC post LR,
      salvage liver transplant (SLT) was first proposed in 2000. However, most patients
      with recurrent HCC considered for SLT are untransplantable cases due to HCC
      recurrence beyond MC or comorbidity. Thus, the strategy of opting for SLT results
      in the loss of the opportunity of LT for these patients. Some authors proposed
      the concept of "de principe liver transplant" (i.e., prophylactic LT before HCC
      recurrence) to prevent losing the chance of LT for these potential candidates.
      Factors associated with the failure of SLT will be dissected and discussed in
      three parts: Patient, tumor, and underlying liver disease. Regarding patient
      related factors, the rate of transplantability depends on patient compliance.
      Patients without regular follow-up tend to develop HCC recurrence beyond MC at
      the time of tumor detection. Advancing age is another factor related to severe
      comorbidities when LT is considered for HCC recurrence, and these elderly
      candidates become ineligible as time goes by. Regarding tumor-related factors,
      histopathological features of the resected specimen are used mostly for
      determining the prognosis of early HCC recurrences. Such prognostic factors
      include the presence of microvascular invasion, poor tumor differentiation, the
      presence of microsatellites, the presence of multiple tumors, and the presence of
      the gene-expressing signature associated with aggressive HCC. These prognostic
      factors might be used as a selection tool for SLT or prophylactic LT, while
      remaining mindful of the fact that most of them are also prognostic factors for
      post-transplant HCC recurrence. Regarding underlying liver disease-related
      factors, progression of chronic viral hepatitis and high viral load may
      contribute to the development of late (de novo) HCC recurrence as a consequence
      of sustained inflammatory reaction. However, correlation between the severity of
      liver fibrosis and tumor recurrence is still controversial. Some prognostic
      scoring systems that integrate these three factors have been proposed to predict
      recurrence patterns after LR for HCC. Theoretically, after excluding patients
      with high risk of post-transplant HCC recurrence, either by observation of a
      cancer-free period or by measurement of biological factors (such as alpha
      fetoprotein), prophylactic LT following curative resection of HCC could be
      considered for selected patients with high risk of recurrence to provide longer
      survival.

PMID- 27872683
TI  - Safe and effective sofosbuvir-based therapy in patients with mental health
      disease on hepatitis C virus treatment.
AB  - AIM: To study impact of baseline mental health disease on hepatitis C virus (HCV)
      treatment; and Beck's Depression Inventory (BDI) changes with sofosbuvir- and
      interferon-based therapy. METHODS: This is a retrospective cohort study of
      participants from 5 studies enrolled from single center trials conducted at the
      Clinical Research Center of the National Institutes of Health, Bethesda, MD,
      United States. All participants were adults with chronic HCV genotype 1 infection
      and naive to HCV therapy. Two of the studies included HCV mono-infected
      participants only (SPARE, SYNERGY-A), and 3 included human immunodeficiency virus
      (HIV)/HCV co-infected participants only (ERADICATE, PFINPK, and ALBIN). Patients
      were treated for HCV with 3 different regimens: Sofosbuvir and ribavirin in the
      SPARE trial, ledipasvir and sofosbuvir in SYNERGY-A and ERADICATE trials, and
      pegylated interferon (IFN) and ribavirin for 48 wk in the PIFNPK and ALBIN
      trials. Participants with baseline mental health disease (MHD) were identified
      (defined as either a DSM IV diagnosis of major depression, bipolar disorder,
      schizophrenia, generalized anxiety, and post-traumatic stress disorder or
      requiring anti-depressants, antipsychotics, mood stabilizers or psychotropics
      prescribed by a psychiatrist). For our first aim, we compared sustained virologic
      response (SVR) and adherence (pill counts, study visits, and in 25 patients,
      blood levels of the sofosbuvir metabolite, GS-331007) within each study. For our
      second aim, only patients with HIV coinfection were evaluated. BDI scores were
      obtained pre-treatment, during treatment, and post-treatment among participants
      treated with sofosbuvir-based therapy, and compared to scores from participants
      treated with interferon-based therapy. Statistical differences for both aims were
      analyzed by Fisher's Exact, and t-test with significance defined as a P value
      less than 0.05. RESULTS: Baseline characteristics did not differ significantly
      between all participants with and without MHD groups treated with sofosbuvir
      based therapy. Among patients treated with sofosbuvir-based therapy, the
      percentage of patients with MHD who achieved SVR was the same as those without
      (SPARE: 60.9% of those MHD compared to 67.6% in those without, P = 0.78; SYNERGY
      A: 100% of both groups; ERADICATE: 100% compared to 97.1%). There was no
      statistically significant difference in pill counts, adherence to study visits
      between groups, nor mean serum concentrations of GS-331007 for each group at week
      2 of treatment (P = 0.72). Among patients with HIV co-infection, pre-treatment
      BDI scores were similar among patients treated with sofosbuvir, and those treated
      with interferon (sofosbuvir-based 5.24, IFN-based 6.96; P = 0.14); however, a
      dichotomous effect on was observed during treatment. Among participants treated
      with directly acting antiviral (DAA)-based therapy, mean BDI scores decreased
      from 5.24 (pre-treatment) to 3.28 during treatment (1.96 decrease, P = 0.0034)
      and 2.82 post-treatment. The decrease in mean score from pre- to post-treatment
      was statistically significant (-2.42, P = 0.0012). Among participants treated
      with IFN-based therapy, mean BDI score increased from 6.96 at pre-treatment to
      9.19 during treatment (an increase of 2.46 points, P = 0.1), and then decreased
      back to baseline post-treatment (mean BDI score 6.3, P = 0.54). Overall change in
      mean BDI scores from pre-treatment to during treatment among participants treated
      with DAA-based and IFN-therapy was statistically significant (-1.96 and +2.23,
      respectively; P = 0.0032). This change remained statistically significant when
      analysis was restricted to participants who achieved SVR (-2.0 and +4.36,
      respectively; P = 0.0004). CONCLUSION: Sofosbuvir-based therapy is safe and well
      tolerated in patients with MHD. A decline in BDI associated with sofosbuvir-based
      HCV treatment suggests additional MHD benefits, although the duration of these
      effects is unknown.

PMID- 27872684
TI  - Liver resection for early hepatocellular cancer: Comparison of centers in 3
      different countries.
AB  - AIM: To compare patients who underwent resection of early stage hepatocellular
      cancer (HCC) in three different countries. METHODS: This retrospective study
      characterizes 573 stage I/II HCC patients treated with liver resection in 3
      tertiary-referral centers: Tokyo (n = 250), Honolulu (n = 146) and Shanghai (n =
      177). RESULTS: Shanghai patients were younger, predominantly male, hepatitis-B
      seropositive (94%) and cirrhotic (93%). Tokyo patients were older and more likely
      to have hepatitis-C (67%), smaller tumors, low albumin, and normal alpha
      fetoprotein. The Honolulu cohort had the largest tumors and 30% had no viral
      hepatitis. Age-adjusted mortality at 1 and 5-years were lower in the Tokyo cohort
      compared to Honolulu and there was no difference in mortality between Shanghai
      and Honolulu cohorts. Elevated alpha-fetoprotein, low albumin and tumor > 5 cm
      were associated with increased 1-year mortality. These factors and cirrhosis were
      independently associated with increased 5-year mortality. Independent risk
      factors of survival varied when examined separately by center. CONCLUSION: The
      profile of early-stage HCC patients is strikingly different across countries and
      likely contributes to survival differences. Underlying differences in patient
      populations including risk factors/comorbidities influencing disease progression
      may also account for variation in outcomes.

PMID- 27872681
TI  - Alcohol use disorder and its impact on chronic hepatitis C virus and human
      immunodeficiency virus infections.
AB  - Alcohol use disorder (AUD) and hepatitis C virus (HCV) infection frequently co
      occur. AUD is associated with greater exposure to HCV infection, increased HCV
      infection persistence, and more extensive liver damage due to interactions
      between AUD and HCV on immune responses, cytotoxicity, and oxidative stress.
      Although AUD and HCV infection are associated with increased morbidity and
      mortality, HCV antiviral therapy is less commonly prescribed in individuals with
      both conditions. AUD is also common in human immunodeficiency virus (HIV)
      infection, which negatively impacts proper HIV care and adherence to
      antiretroviral therapy, and liver disease. In addition, AUD and HCV infection are
      also frequent within a proportion of patients with HIV infection, which
      negatively impacts liver disease. This review summarizes the current knowledge
      regarding pathological interactions of AUD with hepatitis C infection, HIV
      infection, and HCV/HIV co-infection, as well as relating to AUD treatment
      interventions in these individuals.

PMID- 27872685
TI  - Mortality and rebleeding following variceal haemorrhage in liver cirrhosis and
      periportal fibrosis.
AB  - AIM: To investigate mortality and rebleeding rate and identify associated risk
      factors at 6 wk and 5 d following acute variceal haemorrhage in patients with
      liver cirrhosis and schistosomal periportal fibrosis. METHODS: This is a
      prospective study conducted during the period from March to December 2014.
      Patients with portal hypertension presenting with acute variceal haemorrhage
      secondary to either liver cirrhosis (group A) or schistosomal periportal fibroses
      (group B) presenting within 24 h of the onset of the bleeding were enrolled in
      the study and followed for a period of 6 wk. Analysis of data was done by
      Microsoft Excel and comparison between groups was done by Statistical Package of
      Social Sciences version 20 to calculate means and find the levels of statistical
      differences and define the mortality rates, the P value of < 0.05 was considered
      to be significant. RESULTS: A total of 94 patients were enrolled in the study.
      Thirty-two patients (34%) had liver cirrhosis (group A) and 62 (66%) patients had
      periportal fibrosis (group B). Mortality: The 6-wk and 5-d mortality were 53% and
      16% respectively in group A compared to 10% and 0% in group B (P value < 0.000
      and < 0.004). In group A; a Child-Turcotte-Pugh class C and rebleeding within 5 d
      were significantly associated with 5-d mortality (P value < 0.029 and < 0.049
      respectively) and Child- Turcotte-Pugh class C was also a significant risk factor
      for 6-wk mortality (P value < 0.018). In group B; mortality was significantly
      associated with rebleeding within the 6-wk follow-up period and requirement for
      blood transfusion on admission (P value < 0.005 and < 0.049). Rebleeding: The 6
      wk and 5-d rebleeding rate in group A were 56% and 25% respectively compared to
      32% and 3% in group B (P value < 0.015 and < 0.002). Clinical presentation with
      encephalopathy was a significant risk factor for 5 d rebleeding in group A (P
      value < 0.005) while grade III periportal fibrosis and requirement for blood
      transfusion on admission were significant risk factors for 6-wk rebleeding in
      group B (P value < 0.004 and < 0.02). CONCLUSION: The 6-wk and 5-d mortality and
      rebleeding rate were significantly higher in patients with liver cirrhosis
      compared to patients with schistosomal periportal fibrosis.

PMID- 27872687
TI  - Determining the Molecular Pathways Underlying the Protective Effect of Non
      Steroidal Anti-Inflammatory Drugs for Alzheimer's Disease: A Bioinformatics
      Approach.
AB  - Alzheimer's disease (AD) represents a substantial unmet need, due to increasing
      prevalence in an ageing society and the absence of a disease modifying therapy.
      Epidemiological evidence shows a protective effect of non steroidal anti
      inflammatory (NSAID) drugs, and genome wide association studies (GWAS) show
      consistent linkage to inflammatory pathways; both observations suggesting anti
      inflammatory compounds might be effective in AD therapy although clinical trials
      to date have not been positive. In this study, we use pathway enrichment and
      fuzzy logic to identify pathways (KEGG database) simultaneously affected in both
      AD and by NSAIDs (Sulindac, Piroxicam, Paracetamol, Naproxen, Nabumetone,
      Ketoprofen, Diclofenac and Aspirin). Gene expression signatures were derived for
      disease from both blood (n = 344) and post-mortem brain (n = 690), and for drugs
      from immortalised human cell lines exposed to drugs of interest as part of the
      Connectivity Map platform. Using this novel approach to combine datasets we find
      striking overlap between AD gene expression in blood and NSAID induced changes in
      KEGG pathways of Ribosome and Oxidative Phosphorylation. No overlap was found in
      non NSAID comparison drugs. In brain we find little such overlap, although
      Oxidative Phosphorylation approaches our pre-specified significance level. These
      findings suggest that NSAIDs might have a mode of action beyond inflammation and
      moreover that their therapeutic effects might be mediated in particular by
      alteration of Oxidative Phosphorylation and possibly the Ribosome pathway. Mining
      of such datasets might prove increasingly productive as they increase in size and
      richness.

PMID- 27872686
TI  - Engineering Translation in Mammalian Cell Factories to Increase Protein Yield:
      The Unexpected Use of Long Non-Coding SINEUP RNAs.
AB  - Mammalian cells are an indispensable tool for the production of recombinant
      proteins in contexts where function depends on post-translational modifications.
      Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the
      production of therapeutic proteins, including monoclonal antibodies (MAbs). To
      improve expression and stability, several methodologies have been adopted,
      including methods based on media formulation, selective pressure and cell- or
      vector engineering. This review presents current approaches aimed at improving
      mammalian cell factories that are based on the enhancement of translation. Among
      well-established techniques (codon optimization and improvement of mRNA secondary
      structure), we describe SINEUPs, a family of antisense long non-coding RNAs that
      are able to increase translation of partially overlapping protein-coding mRNAs.
      By exploiting their modular structure, SINEUP molecules can be designed to target
      virtually any mRNA of interest, and thus to increase the production of secreted
      proteins. Thus, synthetic SINEUPs represent a new versatile tool to improve the
      production of secreted proteins in biomanufacturing processes.

PMID- 27872688
TI  - Functional Roles for Exosomal MicroRNAs in the Tumour Microenvironment.
AB  - Extracellular microRNAs are released from cells both passively and actively. The
      presence of these microRNAs in the tumour microenvironment (TME) can
      significantly impact on the plasticity of cancer cells leading to the promotion
      of metastatic and angiogenic processes. These extracellular microRNAs can act not
      only on other cancer cells, but also cells present in the TME, such as immune
      cells, endothelial cells, fibroblasts, and others acting to subvert the host
      immune system and drive tumour progression. In this review we highlight the
      current understanding of both the mechanisms by which microRNAs are released from
      tumour cells and the downstream functional effects that extracellular microRNAs
      have on recipient cells.

PMID- 27872689
TI  - Role of Nitric Oxide on Dopamine Release and Morphine-Dependency.
AB  - The catastrophic effects of opioids use on public health and the economy are
      documented clearly in numerous studies. Repeated morphine administration can lead
      to either a decrease (tolerance) or an increase (sensitization) in its behavioral
      and rewarding effects. Morphine-induced sensitization is a major problem and
      plays an important role in abuse of the opioid drugs. Studies reported that
      morphine may exert its effects by the release of nitric oxide (NO). NO is a
      potent neuromodulator, which is produced by nitric oxide synthase (NOS). However,
      the exact role of NO in the opioid-induced sensitization is unknown. In this
      study, we reviewed the role of NO on opioid-induced sensitization in 2 important,
      rewarding regions of the brain: nucleus accumbens and ventral tegmentum. In
      addition, we focused on the contribution of NO on opioid-induced sensitization in
      the limbic system.

PMID- 27872690
TI  - The Effects of Kainic Acid-Induced Seizure on Gene Expression of Brain
      Neurotransmitter Receptors in Mice Using RT2 PCR Array.
AB  - INTRODUCTION: Kainic acid (KA) induces neuropathological changes in specific
      regions of the mouse hippocampus comparable to changes seen in patients with
      chronic temporal lobe epilepsy (TLE). According to different studies, the
      expression of a number of genes are altered in the adult rat hippocampus after
      status epilepticus (SE) induced by KA. This study aimed to quantitatively
      evaluate changes in the gene expression of brain neurotransmitter receptors one
      week after administration of kainic acid in the mouse hippocampus. METHODS: We
      used 12 BALB/c mice in this study and randomly divided them into 2 groups. To
      both groups, saline (IP) was administered for 7 days, and on the last day, KA (10
      mg/kg, IP) was injected 30 minutes after administration of saline. Subsequently,
      behavioural changes were observed in mice. Then, in one group (1 day group), 2
      hours and in another group (7 days group), 7 days after KA administration, the
      hippocampus tissue of mice was removed and used for gene expression analyses.
      Total brain RNA was isolated and reversely transcribed. We performed qPCR using
      RT2 Profiler TMPCR Array Mouse Neurotransmitter Receptors and Regulators (QIAGEN)
      containing primers for 84 genes. In this regard, we selected 50 related genes for
      KA model. RESULTS: Our results showed significant changes in the gene expression
      of GABAA subunits receptors, including alpha1-alpha3, alpha5, alpha6, beta2,
      beta3, gamma1, rho, and rho1-2 on day 7 compared with the day 1. CONCLUSION:
      Expression of both inhibitory and excitatory receptors changed after one week.
      Further studies are needed to find more molecular changes in the gene expression
      of brain neurotransmitter receptors and regulators over longer periods of time in
      KA models using RT2 PCR array.

PMID- 27872691
TI  - Locally Estimated Hemodynamic Response Function and Activation Detection
      Sensitivity in Heroin-Cue Reactivity Study.
AB  - INTRODUCTION: A fixed hemodynamic response function (HRF) is commonly used for
      functional magnetic resonance imaging (fMRI) analysis. However, HRF may vary from
      region to region and subject to subject. We investigated the effect of locally
      estimated HRF (in functionally homogenous parcels) on activation detection
      sensitivity in a heroin cue reactivity study. METHODS: We proposed a novel
      exploratory method for brain parcellation based on a probabilistic model to
      segregate the brain into spatially connected and functionally homogeneous
      components. Then, we estimated HRF and detected activated regions in response to
      an experimental task in each parcel using a joint detection estimation (JDE)
      method. We compared the proposed JDE method with the general linear model (GLM)
      that uses a fixed HRF and is implemented in FEAT (as a part of FMRIB Software
      Library, version 4.1). RESULTS: 1) Regions detected by JDE are larger than those
      detected by fixed HRF, 2) In group analysis, JDE found areas of activation not
      detected by fixed HRF. It detected drug craving a priori "regions-of-interest" in
      the limbic lobe (anterior cingulate cortex [ACC], posterior cingulate cortex
      [PCC] and cingulate gyrus), basal ganglia, especially striatum (putamen and head
      of caudate), and cerebellum in addition to the areas detected by the fixed HRF
      method, 3) JDE obtained higher Z-values of local maxima compared to those
      obtained by fixed HRF. CONCLUSION: In our study of heroin cue reactivity, our
      proposed method (that estimates HRF locally) outperformed the conventional GLM
      that uses a fixed HRF.

PMID- 27872692
TI  - Protective Effects of Vitamin E Consumption against 3MT Electromagnetic Field
      Effects on Oxidative Parameters in Substantia Nigra in Rats.
AB  - INTRODUCTION: Electromagnetic fields (EMFs) can influence the biological system
      by the formation of free radicals in cells. The EMFs are able to deteriorate
      defense system against free radicals that leads to oxidative stress (OS). Lipid
      peroxidation process (LPO) is an index of oxidative stress, and the
      Malandialdehyde (MDA) is the final product of LPO. Vitamin E is the most
      important antioxidant which inhibits the LPO process. The aim of this study was
      to evaluate the effects of 3MT EMF exposure on oxidative stress parameters in
      substantia nigra and the role of vitamin E in reducing oxidative stress and
      preventing of LPO process. METHODS: 40 male Wistar rats were randomly divided
      into 4 groups: 1) Control group: received standard food without exposure to EMF
      and without consumption of vitamin E, 2) Experimental group 1: was exposed to EMF
      (3MT) 4 h/day for 50 days, 3) The experimental group 2: received 200 mg/kg
      vitamin E with gavage every day and also was exposed to EMF (3MT) 4 h/day for 50
      days, 4) Sham group: received water with gavage for 50 days. RESULTS: A
      significant increase in MDA levels and Glutation peroxidase (GSH-Px) activity of
      the substantia nigra following 50 days exposure to EMF was detected, but the
      superoxide dismutase (SOD) activity was decreased. Exposure did not change total
      antioxidant capacity (TAC) levels in plasma. Vitamin E treatment significantly
      prevented the increase of the MDA levels and GSHPx activity and also prevented
      the decrease of SOD activity in tissue but did not alter TAC levels. The GSH-Px
      activity increased because the duration and intensity of exposure were not enough
      to decrease it. CONCLUSION: We demonstrated two important findings; that 50 days
      exposure to 3 MT electromagnetic field caused oxidative stress by increasing the
      levels of MDA, and decreasing SOD activity in the substantia nigra; and that
      treatment with the vitamin E significantly prevented the oxidative stress and
      lipid peroxidation.

PMID- 27872693
TI  - Obsessive-Compulsive Disorder in Hospitalized Patients with Schizophrenia.
AB  - INTRODUCTION: Comorbid obsessive-compulsive disorder (OCD) has been reported
      among patients with schizophrenia in other countries. But, the literature is not
      well-documented on this issue in Iran (Persia). The present study aimed to
      investigate the prevalence and severity of OCD and some of its related factors in
      a group of patients with schizophrenia in Iran. METHODS: This is a cross
      sectional study. A total of 150 hospitalized patients with schizophrenia were
      recruited at Razi Psychiatric Hospital in Tehran, Iran. Demographic and clinical
      checklists, as well as the Yale-Brown obsessive-compulsive scale (Y-BOCS), scale
      for assessment of negative symptoms (SANS), and scale for assessment of positive
      symptoms (SAPS) were administered to collect data. OCD was the dependent variable
      and independent variables included age, sex, severity of positive and negative
      symptoms, duration of schizophrenic disorder, the number of hospitalizations, and
      antipsychotic medications administered to them. Data were analyzed by analysis of
      variance (ANOVA), Chi-square, and T-test. RESULTS: Overall, 31.3% of patients had
      OCD with an average severity of 12.81(SD=10.27). The prevalence of OCD was not
      affected by the number of psychiatric hospitalizations for schizophrenia or the
      duration of schizophrenic disorder. The severity of OCD significantly reduced as
      the duration of schizophrenia and the severity of negative symptoms increased.
      CONCLUSION: OCD was found among a considerable proportion of the study sample.
      OCD may be associated with exacerbating schizophrenic symptoms. Therefore,
      psychiatrists should consider the simultaneous treatment of OCD and
      schizophrenia. Further studies are suggested in this issue.

PMID- 27872694
TI  - Long-Term Treatment by Vitamin B1 and Reduction of Serum Proinflammatory
      Cytokines, Hyperalgesia, and Paw Edema in Adjuvant-Induced Arthritis.
AB  - INTRODUCTION: Immune system is involved in the etiology and pathophysiology of
      inflammation and vitamins are important sources of substances inducing
      nonspecific immunomodulatory effects. Given the proinflammatory role of cytokines
      in the inflammation and pain induction, this study aimed to assess the effects of
      long-term administration of vitamin B1 on the proinflammatory cytokines, edema,
      and hyperalgesia during the acute and chronic phases of adjuvant-induced
      arthritis. METHODS: On the first day of study, inflammation was induced by
      intraplantar injection of complete Freund's adjuvant (CFA) in the hindpaws of
      rats. Vitamin B1 at doses of 100, 150, and 200 mg/kg was administrated
      intraperitoneally during 21 days of the study. Antinociceptive and anti
      inflammatory effects of vitamin B1 were also compared to indomethacin (5 mg/kg).
      Inflammatory symptoms such as thermal hyperalgesia and paw edema were measured by
      radiant heat and plethysmometer, respectively. Serum TNF-alpha and IL-1beta
      levels were checked by rat standard enzyme-linked immune sorbent assay (ELISA)
      specific kits. RESULTS: The results indicated that vitamin B1(150 and 200 mg/kg)
      attenuated the paw edema, thermal hyperalgesia, and serum levels of TNF-alpha and
      IL-1beta during both phases of CFA-induced inflammation in a dose-dependent
      manner. Effective dose of vitamin B1(150 mg/kg) reduced inflammatory symptoms and
      serum levels of TNF-alpha and IL-1beta compare to indomethacin during the chronic
      phase of inflammation. CONCLUSION: Anti-inflammatory and antihyperalgesic effects
      of vitamin B1 during CFA-induced arthritis, more specifically after chronic
      vitamin B1 administration, suggest its therapeutic property for inflammation.

PMID- 27872695
TI  - Reduction of the Morphine Maintenance by Blockade of the NMDA Receptors during
      Extinction Period in Conditioned Place Preference Paradigm of Rats.
AB  - INTRODUCTION: Activation of N-methyl-d-aspartate (NMDA) glutamate receptors in
      the nucleus accumbens is a component of drug-induced reward mechanism. In
      addition, NMDA receptors play a major role in brain reward system and activation
      of these receptors can change firing pattern of dopamine neurons. Blockade of
      glutamatergic neurotransmission reduces the expression of conditioned place
      preference (CPP) induced by morphine. Therefore, in this study, by using an NMDA
      receptor antagonist, DL-2-Amino-5-phosphonopentanoic acid sodium salt (AP5), the
      role of NMDA receptors on the maintenance and reinstatement of morphine-CPP was
      investigated. METHODS: Forty-three adult male albino Wistar rats were used in
      this study. After subcutaneous administration of effective dose of morphine (5
      mg/kg) during CPP paradigm, the animals received intracerebroventricular doses of
      AP5(1, 5, and 25 mM/5MUL saline) during extinction period (free morphine stage).
      Conditioning score was recorded during extinction period and reinstatement phase.
      Besides, another group of the animals received a single dose administration of
      AP5(5 mM) just before the administration of ineffective dose of morphine (1
      mg/kg) in reinstatement phase. RESULTS: The results revealed that two doses of
      this antagonist (5 and 25 mM) significantly shortened the extinction period of
      morphine-CPP but did not reduce reinstatement induced by priming dose of
      morphine. Moreover, the single dose administration of AP5(5 mM) just before prime
      morphine injection decreased reinstatement of morphine-CPP. CONCLUSION: These
      findings indicate that blockade of NMDA receptors during extinction period
      reduces maintenance but not reinstatement of morphine. In addition, blocking
      these receptors in reinstatement phase decreases reinstatement to extinguished
      morphine.

PMID- 27872696
TI  - Incidence and Clinical Outcome of Patients with Hypertensive Acute Ischemic
      Stroke: An Update from Tertiary Care Center of Central India.
AB  - INTRODUCTION: We evaluated the incidence and clinical outcome of patients with
      hypertensive acute ischemic stroke (AIS) admitted to a tertiary care center in
      Central India. In addition, we examined the status of stroke biomarkers namely
      neuron-specific enolase (NSE), glial specific protein (S-100betabeta), and inter
      alpha-trypsin inhibitor heavy chain 4(ITIH4) in the serum of patients suffering
      from AIS with hypertension (HTN) and without HTN. METHODS: A total of 104
      patients with AIS were enrolled for the study. Clinical outcome and stroke
      biomarker levels were evaluated in them at the time of hospital discharge and
      then followed at 12 months and 18 months after hospital discharge. RESULTS: HTN
      is a major risk factor associated with 67%(70.104) of patients with AIS.
      Multivariate analysis suggests higher odds of 4.088(95%Cl, 0.721-23.179) and
      2.437(95%Cl, 0.721-23.179) for 12 and 18 months outcome in patients with AIS and
      HTN, respectively. Serum NSE and S-100betabeta decreased at the time of discharge
      as compared to admission level in improved patients suffering from AIS with or
      without HTN, whereas levels of ITIH4 peptides 2 and 7 increased at the time of
      discharge (compared to its admission level) only in improved patients with AIS
      regardless of HTN or non-HTN condition. CONCLUSION: HTN is one of the major risk
      factors associated with higher risk of AIS as well as long-term unfavourable
      outcome after AIS in Central India region. NSE, S-100betabeta, and ITIH4 were
      found to be independent predictors of outcome in patients with AIS irrespective
      of HTN and non-HTN condition.

PMID- 27872697
TI  - Co-occurrence of Pituitary Adenoma with Suprasellar and Olfactory Groove
      Meningiomas.
AB  - INTRODUCTION: The co-existence of pituitary adenoma and meningioma is extremely
      rare. It is even rarer in patients with no previous known risk factors for either
      tumour. Here, we present a case of synchronous non-functioning pituitary adenoma
      with suprasellar and olfactory groove meningiomas in a patient without previous
      irradiation. METHODS: The tumours were diagnosed on MRI in the 65-year-old
      patient who presented with patchy visual deficits. The decision was made to
      undergo surgery for resection of the suprasellar meningioma and the pituitary
      adenoma, leaving the small olfactory groove meningioma intact. Extended
      endoscopic transsphenoidal surgery was performed. RESULTS: Macroscopic clearance
      was achieved for pituitary macroadenoma and suprasellar meningioma.
      Postoperatively, visual field tsting and pituitary axis hormonal levels were
      normal. The pituitary macroadenoma was confirmed to be a non-functioning
      pituitary adenoma. The meningioma was diagnosed to be of WHO grade 1. CONCLUSION:
      The rationale for choosing such management option, including its risks and
      benefits in this challenging patient is discussed.

PMID- 27872698
TI  - The role of exosomes contents on genetic and epigenetic alterations of recipient
      cancer cells.
AB  - Exosomes, as a mediator of cell-to-cell transfer of genetic information, act an
      important role in intercommunication between tumor cells and their niche
      including fibroblasts, endothelial cells, adipocytes and monocytes. Several
      studies have shown that tumor cells can influence their neighboring cells by
      releasing exosomes. These exosomes provide signaling cues for stimulation,
      activation, proliferation and differentiation of cells. Exosomes contain mRNAs,
      microRNAs (miRNA), and proteins that could be transferred to target cells
      inducing genetic and epigenetic changes. By facilitating the horizontal transfer
      of bioactive molecules such as proteins, RNAs and microRNAs, they are now thought
      to have vital roles in tumor invasion and metastases, inflammation, coagulation,
      and stem cell renewal and expansion. The aim of this review article is to discuss
      the significance of exosome-mediated intercellular communication within the tumor
      biology.

PMID- 27872699
TI  - The effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing
      enzymes in selenium and/or iodine deficient rats.
AB  - OBJECTIVES: Particularly in developing countries, selenium and/or iodine
      deficiencies are encountered and use of pesticides in agriculture are not well
      controlled. Fenvalerate is a pyrethroid insectide used in agriculture and has
      applications against a wide range of pests. This study was designed to evaluate
      the effects of fenvalerate on hepatic and cerebral xenobiotic metabolizing enzyme
      activities in the presence of iodine and/or selenium deficiency on a rat model.
      MATERIALS AND METHODS: Iodine and/or selenium deficiency was induced by feeding
      three-week-old Wistar rats with a diet containing <0.005 mg selenium kg-1, and/or
      administering 1% sodium perchlorate in drinking water for 7 weeks. Test groups
      received fenvalerate (100 mg kg-1 BW IP) for the last 7 days. Hepatic and
      cerebral microsomal aniline hydroxylase (CYP2E1) and cytosolic glutathione S
      transferase (GST) activities were determined. Besides, hepatic NADPH-cytochrome
      P450 reductase (P450R), ethoxyresorufin O-deethylase (EROD, CYP1A1/1A2) and
      penthoxyresorufin O-depenthylase (PROD, CYP2B1/2B2), activities were also
      measured. RESULTS: Fenvalerate had a general inductive effect on the hepatic and
      cerebral xenobiotic metabolizing enzyme activities. Moreover, enzyme activities
      were also altered by iodine and/or selenium deficiency, but the effects seemed to
      be enzyme- and tissue-specific. CONCLUSION: The inductive effect of fenvalerate,
      particularly in high dose exposures, may change the metabolism of several
      xenobiotics, including drugs, as well as endogenous substrates. The effects may
      vary depending on the selenium and/or iodine status of individual.

PMID- 27872700
TI  - Pharmacokinetic study of furosemide incorporated PLGA microspheres after oral
      administration to rat.
AB  - OBJECTIVES: The purpose of the current study was to assess the feasibility of
      microspheres from biocompatible polymer for oral bioavailability (BA) enhancement
      of potent sulfonamide- type loop diuretic- Furosemide - which used in the
      treatment of congestive heart failure, caused edema, cirrhosis, renal disease and
      as an adjunct in acute pulmonary edema. The comparatively poor and inconstant BA
      of furosemide, which occurs site-specifically in the stomach and upper small
      intestine, has been ascribed to the poor dissolution of furosemide. MATERIALS AND
      METHODS: In attempt to enhance the drug BA, poly (dl-lactic-co-glycolic acid)
      (PLGA) microspheres of furosemide were obtained using solvent-evaporation method
      and the carrier characteristics were investigated subsequently. RESULTS: The in
      vivo performance of optimum formulation was assessed by pharmacokinetic
      evaluation of drug after orally administration of free and loaded in microspheres
      to rats (4 mg/Kg). For this reason, the concentration of drug in plasma was
      measured by a new developed and sensitive method of HPLC. Acceptable drug loading
      and encapsulation efficiency of microspheres were obtained to be 70.43 and 85.21
      %, respectively. Microspheres provided improved pharmacokinetic parameters (Cmax
      = 147.94 ng/ml, Tmax = 1.92 hr) in rats as compared with pure drug (Cmax = 75.69
      ng/ml, Tmax = 1.5 hr). The obtained AUC of drug in microsphere was 10 fold higher
      than of the free drug. CONCLUSION: The results showed that the prepared
      microspheres successfully improved BA of the poorly water-soluble drug
      effectively.

PMID- 27872701
TI  - Development of 153Sm-DTPA-SPION as a theranostic dual contrast agents in
      SPECT/MRI.
AB  - OBJECTIVES: This study describes the preparation, biodistribution of 153Sm-DTPA
      SPION after intravenous injection in rats. MATERIALS AND METHODS: The chelator
      DTPA dianhydride was conjugated to SPION using a small modification of the well
      known cyclic anhydride method. Conjugation was done at a 1: 4 (SPION:ccDTPA)
      molar ratio. Conjugation reaction was purified with magnetic assorting column
      (MACs) using high gradient magnetic field following incubation, the radio labeled
      conjugate was checked using RTLC method for labeling and purity checked. RESULTS:
      The RTLC showed that labeling yield was above 99% after purification and the
      compound have good in vitro stabilities until 48 hr post injection in the
      presence of human serum. The biodistribution of 153Sm-DTPA-SPION in rats showed
      dramatic uptake in the reticuloendothelial system (RES) and their clearance is so
      fast in other organs especially in the blood. Biodistribution results show that
      after 30 min post injection more than 84% of injected activities were taken up by
      the liver and spleen (about 64% and 20%, respectively). CONCLUSION: Due to
      magnificent uptakes of this radiotracer in the liver and spleen and their fast
      clearance from other tissues, especially in blood, it is suggested that this
      radiotracer would be a potential candidate for RES theranostic purposes.

PMID- 27872702
TI  - Gamma reactivation using the spongy effect of KLF1-binding site sequence: an
      approach in gene therapy for beta-thalassemia.
AB  - OBJECTIVES: beta-thalassemia is one of the most common genetic disorders in the
      world. As one of the promising treatment strategies, fetal hemoglobin (Hb F) can
      be induced. The present study was an attempt to reactivate the gamma-globin gene
      by introducing a gene construct containing KLF1 binding sites to the K562 cell
      line. MATERIALS AND METHODS: A plasmid containing a 192 bp sequence with two
      repeats of KLF1 binding sites on beta-globin and BCL11A promoters was constructed
      and used to transfect the K562 cell line. Positive selection was performed under
      treatment with 150 MUg/ml hygromycin B. The remaining cells were expanded and
      harvested on day 28, and genomic DNA was extracted. The PCR was carried out to
      verify insertion of DNA fragment to the genome of K562 cells. The cells were
      differentiated with 15 MUg/ml cisplatin. Flowcytometry was performed to identify
      erythroid differentiation by detection of CD235a+ cells. Real-time RT-PCR was
      performed to evaluate gamma-globin expression in the transfected cells. RESULTS:
      A 1700 bp fragment was observed on agarose gel as expected and insertion of DNA
      fragment to the genome of K562 cells was verified. Totally, 84% of cells were
      differentiated. The transfected cells significantly increased gamma-globin
      expression after differentiation compared to untransfected ones. CONCLUSION: The
      findings demonstrate that the spongy effect of KLF1-binding site on BCL11A and
      beta-globin promoters can induce gamma-globin expression in K562 cells. This
      novel strategy can be promising for the treatment of beta-thalassemia and sickle
      cell disease.

PMID- 27872704
TI  - Effects of sex steroid hormones on neuromedin S and neuromedin U2 receptor
      expression following experimental traumatic brain injury.
AB  - OBJECTIVES: Neuroprotective effects of female gonadal steroids are mediated
      through several pathways involving multiple peptides and receptors after
      traumatic brain injury (TBI). Two of these peptides are including the regulatory
      peptides neuromedin U (NMU) and neuromedin S (NMS), and their common receptor
      neuromedin U2 receptor (NMUR2). This study investigates the effects of
      physiological doses of estradiol and progesterone on brain edema, NMS and NMU as
      well as NMUR2 expression following TBI. MATERIALS AND METHODS: Ovariectomized
      female rats were given high-and low-dose of female sex steroid hormones through
      implantation of capsules for a week before trauma. The brain NMUR2 expression,
      prepro-NMS expression, NMU content, and water content (brain edema) were
      evaluated 24 hr after TBI induced by Marmarou's method. RESULTS: Percentage of
      brain water content in high- and low-dose estradiol, and in high- and low- dose
      progesterone was less than vehicle (P<0.01). Results show high expression of
      prepro-NMS in high dose progesterone (TBI-HP) rats compared to the high dose
      estrogen (TBI-HE), as well as vehicle (P<0.01). NMU content in low-dose
      progesterone (TBI-LP) group was more than that of vehicle group (P<0.001).
      Furthermore a difference in NMU content observed between TBI-HP compared to TBI
      HE, and vehicle (P<0.05). The NMUR2 mRNA expression revealed an upregulation in
      TBI-HP rats compared to the TBI-HE group (P<0.001). CONCLUSION: Findings indicate
      that progesterone attenuates brain edema and induces an increase in NMS and its
      receptor which may mediate the anti-edematous effect of progesterone after TBI.

PMID- 27872705
TI  - Sophora alopecuroides L. var. alopecuroides alleviates morphine withdrawal
      syndrome in mice: involvement of alkaloid fraction and matrine.
AB  - OBJECTIVES: Evaluation of the Sophora alopecuroides var. alopecuroides seed
      effects on morphine withdrawal syndrome in mice and determination of the alkaloid
      composition of the seed total extract. MATERIALS AND METHODS: The effects of the
      seed total extract, alkaloid fraction and major compound matrine on the mice
      morphine withdrawal syndrome were compared to saline and methadone. Mice were
      made dependent on morphine by morphine sulfate injection 3 times a day for 3
      days. The withdrawal jumping and diarrhea were induced by administration of
      naloxone 2 hr after the 10th injection of morphine sulfate on the day 4. The
      total extract (100, 200, 300 mg/kg), alkaloid fraction (5, 10, 20 mg/kg), matrine
      (5, 15, 30 mg/kg), methadone (10 mg/kg) or saline were injected 30 min before
      naloxone. All drugs were administered by subcutaneous injection. The total
      extract alkaloid composition was also determined by gas chromatography (GC) and
      GC-MS analysis. RESULTS: All doses of the total extract, alkaloid fraction and
      matrine as well as methadone decreased jumping and diarrhea significantly
      compared to the saline. The effects of the total extract and alkaloid fraction
      were not significantly different from methadone. But, there were significant
      differences between the effects of matrine and methadone. Matrine, cytisine,
      sophoridine, n-methyl cytisine, sophocarpine and sophoramine were the major
      alkaloids. There was no nicotine in the total extract. CONCLUSION: S.
      alopecuroides var. alopecuroides suppresses opioid withdrawal with efficacy
      comparable to methadone. Matrine may be one of the alkaloids responsible for the
      effect of the plant.

PMID- 27872703
TI  - Crocin prevents haloperidol-induced orofacial dyskinesia: possible an antioxidant
      mechanism.
AB  - OBJECTIVES: Long-term treatment with antipsychotics causes serious side effects
      such as tardive dyskinesia that characterized by abnormal movements in the
      orofacial region. Oxidative stress in the brain specific area is implicated in
      the pathophysiology of tardive dyskinesia. In this study the protective effect of
      crocin on haloperidol-induced orofacial dyskinesia was evaluated. MATERIALS AND
      METHODS: Haloperidol (1 mg/kg, IP) and crocin (10, 20 and 40 mg/kg, IP) were
      administrated to rats for 21 days. Behavioral assessments such as orofacial
      dyskinesia movements, open field test and elevated plus maze (EPM) were evaluated
      every week. Malondealdehyde (MDA) and glutathione (GSH) levels in the
      hippocampus, cortex and striatum were also measured. RESULTS: Haloperidol
      increased vacuous chewing movements (VCMs) and tongue protrusions (TPs) in rats
      and co-administration of crocin (20 and 40 mg/kg) significantly reduced them.
      Furthermore, haloperidol decreased the locomotor and exploratory activities
      (rearing) in the open field test and decreased the percentage of entries into
      open arms and the percentage of the time spent on open arms in the EPM.
      Pretreatment with crocin (10 mg/kg) modified haloperidol effects on these
      behavioral parameters. Haloperidol induced lipid peroxidation in three brain
      regions, whereas crocin co-administration reduced the MDA and restored the
      decreased GSH levels. CONCLUSION: Our finding suggests that oxidative stress has
      an important role in the development of tardive dyskinesia. Crocin showed
      protective effect against haloperidol induced tardive dyskinesia and as a potent
      naturally antioxidant could be a new and useful drug and a possible therapeutic
      option for the treatment of tardive dyskinesia.

PMID- 27872706
TI  - Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as
      efficient gene delivery vectors.
AB  - OBJECTIVES: In recent years, polypropyleneimine (PPI) dendrimers have attracted
      great interest as non-viral gene delivery systems because of their attractive
      features including highly branched architecture with number of reactive end
      groups. However, without being structurally modified, they are not efficient gene
      carriers. In the present study, generation 2 and 3 (G2 and G3) of PPI dendrimers
      were conjugated with alkylcarboxylate groups as linker to enhance the
      transfection efficiency while maintaining their low cell toxicity. MATERIALS AND
      METHODS: First, 10-bromodecanoic acid was covalently attached to all available
      surface primary amines of PPI G2 and G3 to increase their lipophilicity. In the
      subsequent step, PPIs were conjugated to the alkylcarboxylate groups of
      alkylcarboxylate-PPI derivatives to increase the number of surface primary
      amines. Physicochemical properties of modified PPIs were determined. Transfection
      experiments (using both luciferase and green fluorescent protein (GFP)-
      expressing plasmids) and cytotoxicity assay were performed to evaluate the
      efficiency of the final derivatives. RESULTS: Fabricated vectors condensed DNA
      effectively so that polyplexes with appropriate size (below 155 nm) and positive
      surface charge were constructed. Cross-linked low molecular weight PPIs (G2 or
      G3) with decanoate linkage increased transfection efficiency significantly while
      maintaining the low cytotoxicity. PPI G2 derivative exhibited increased buffering
      capacity which is believed to be responsible for better proton sponge mechanism
      leading to higher transfection efficiency. CONCLUSION: Our results indicated that
      oligomerization of low molecular weight PPI (PPI G2-alkyl-PPI G2 conjugate) could
      be an approach to increase the transfection efficiency and to lower the
      cytotoxicity of low molecular weight polycations.

PMID- 27872707
TI  - Biochemical characterization of PE_PGRS61 family protein of Mycobacterium
      tuberculosis H37Rv reveals the binding ability to fibronectin.
AB  - OBJECTIVES: The periodic binding of protein expressed by Mycobacterium
      tuberculosis H37Rv with the host cell receptor molecules i.e. fibronectin (Fn) is
      gaining significance because of its adhesive properties. The genome sequencing of
      M. tuberculosis H37Rv revealed that the proline-glutamic (PE) proteins contain
      polymorphic GC-rich repetitive sequences (PGRS) which have clinical importance in
      pathogenesis events when the host encounters M. tuberculosis H37Rv. The
      functional parts of PE_PGRS family proteins, have not been extensively studied in
      tuberculosis biology. MATERIALS AND METHODS: Fibronectin (10 ng and 20 ng) were
      used for FnBP assay and its enzymatic activities were observed by using various
      protein concentrations. RESULTS: Therefore, in the present work, we cloned,
      expressed, purified and identified a novel PE_PGRS61 (Rv3653) family protein in
      M. tuberculosis H37Rv. Our experiment, observation suggested that at particular
      concentrations of 10 ng and 20 ng of Fn exhibits optimum binding to the purified
      Fibronectin Binding Protein (FnBP), a PE_PGRS61 family protein at 0.20 MUg and
      0.25 MUg concentrations, respectively. Moreover, for better understanding the
      computational analysis, the B-cell and T-cell epitopes prediction prospect some
      amino acid propensity scales with hydrophilicity and antigenic variation index at
      their respective locations. CONCLUSION: Thus, the current findings provide an
      opportunity to illuminate the functions of PE_PGRS61 family protein. So, in this
      point of view, it could be useful to develop a novel therapeutic approach or
      diagnostic pipeline through targeting these fibronectin binding protein (FnBP)
      expressing genes.

PMID- 27872708
TI  - Anti-hyperglycaemic and antioxidant effects of Bidens tripartita and quantitative
      analysis on its active principles.
AB  - OBJECTIVES: Bidens species are used for their antidiabetic properties
      traditionally in many countries. Aim of this study is to evaluate hypoglycaemic
      and antidiabetic activity of Bidens tripartita extract and to identify its active
      compounds through bioactivity guided isolation technique. MATERIALS AND METHODS:
      Hypoglycaemic effects of B. tripartita extract and its sub-extracts were
      investigated in normal and glucose-hyperglycaemic rats. Streptozotocin induced
      diabetic rats were used to examine antidiabetic activity of the extract and its
      sub-extracts after acute and sub-acute administration. Additionally, in vitro
      enzyme inhibitory and antioxidant activities were evaluated. HPLC analyses were
      carried out to determine the active constituents of the extract and its sub
      extracts. RESULTS: Through in vivo bioactivity-guided fractionation process,
      ethyl acetate and n-buthanol sub-extracts were found to have potent antidiabetic
      activity. In vitro enzyme inhibitory activities of the same sub-extracts were
      found to be potent. The highest total phenol, flavonoid contents and radical
      scavenging activity was determined in ethyl acetate sub-extract. According to LC
      MS analyses, chlorogenic acid, luteolin and 7-O-glucoside of luteolin
      (cynaroside) were determined as the main components of the active sub-extracts.
      CONCLUSION: According to our results, B. tripartita has potent antidiabetic
      activity and its active constituents might be beneficial for diabetes and its
      complications.

PMID- 27872709
TI  - The effect of sugar cane molasses on the immune and male reproductive systems
      using in vitro and in vivo methods.
AB  - OBJECTIVES: Sugar cane molasses is a commonly used ingredient in several food
      products. Contrasting reports suggest that molasses may have potential adverse or
      beneficial effects on human health. However, little evidence exists that examines
      the effects of molasses on the different physiological systems. This study
      investigated the effects of sugar cane molasses on various physiological systems
      using in vivo and in vitro methods. MATERIALS AND METHODS: Molasses was
      administered orally to BALB/c, male mice and animals were randomly assigned into
      either a treatment or control group. General physiological changes, body weight
      and molasses intake of animals were monitored. At the end of the exposure period,
      collected blood samples were evaluated for potential toxicity using plasma
      biomarkers and liver enzyme activity. Immunised treated and untreated mice were
      evaluated for antibody titre to determine the effect of molasses on the immune
      response. To investigate the impact of molasses on testicular steroidogenesis,
      testes from both treated and control groups were harvested, cultured and assayed
      for testosterone synthesis. RESULTS: Findings suggest that fluid intake by
      molasses-treated animals was significantly increased and these animals showed
      symptoms of loose faeces. Molasses had no significant effect on body weight,
      serum biomarkers or liver enzyme activity (P>0.05). Immunoglobulin-gamma anti
      antigen levels were significantly suppressed in molasses-treated groups
      (P=0.004). Animals subjected to molasses exposure also exhibited elevated levels
      of testosterone synthesis (P=0.001). CONCLUSION: Findings suggests that molasses
      adversely affects the humoral immune response. The results also promote the use
      of molasses as a supplement to increase testosterone levels.

PMID- 27872710
TI  - Linc-ROR and its spliced variants 2 and 4 are significantly up-regulated in
      esophageal squamous cell carcinoma.
AB  - OBJECTIVES: Similar characteristics of molecular pathways between cellular
      reprogramming events and tumorigenesis have been accentuated in recent years.
      Reprogramming-related transcription factors, also known as Yamanaka factors
      (OCT4, SOX2, KLF4, and c-MYC), are also well-known oncogenes promoting cancer
      initiation, progression, and cellular transformation into cancer stem cells. Long
      non-coding RNAs (lncRNAs) are a major class of RNA molecules with emerging roles
      in stem cell pluripotency, cellular reprogramming, cellular transformation, and
      tumorigenesis. The long intergenic non-coding RNA ROR (lincRNA-ROR, linc-ROR)
      acts as a regulator of cellular reprograming through sponging miR-145 that
      normally negatively regulates the expression of the stemness factors NANOG, OCT4,
      and SOX2. MATERIALS AND METHODS: Here, we employed a real-time PCR approach to
      determine the expression patterns of linc-ROR and its two novel spliced variants
      (variants 2 and 4) in esophageal squamous cell carcinoma (ESCC). RESULTS: The
      quantitative real-time RT-PCR results revealed a significant up-regulation of
      linc-ROR (P=0.0098) and its variants 2 (P=0.0250) and 4 (P=0.0002) in tumor
      samples of ESCC, compared to their matched non-tumor tissues obtained from the
      margin of same tumors. Our data also demonstrated a significant up-regulation of
      variant 4 in high-grade tumor samples, in comparison to the low-grade ones
      (P=0.04). Moreover, the ROC curve analysis demonstrated that the variant 4 of ROR
      has a potential to discriminate between tumor and non-tumor samples (AUC=0.66,
      P<0.05). CONCLUSION: Our data suggest a significant up-regulation of linc-ROR and
      its variants 2 and 4 in ESCC tissue samples.

PMID- 27872711
TI  - Ozone therapy could attenuate tubulointerstitial injury in adenine-induced CKD
      rats by mediating Nrf2 and NF-kappaB.
AB  - OBJECTIVES: This study aims to determine the effects of ozone therapy on
      restoring impaired Nrf2 activation to ameliorate chronic tubulointerstitial
      injury in rats with adenine-induced CKD. MATERIALS AND METHODS: Sprague-Dawley
      rats were fed with 0.75% adenine-containing diet to induce CKD and chronic
      tubulointerstitial injury. Ozone therapy was administered by rectal insufflation.
      After 4 weeks, serum and kidney samples were collected and analyzed. Renal
      function and systemic electrolyte level were detected. Pathological changes in
      kidney were assessed by hematoxylin-eosin staining and Masson trichrome staining.
      Nrf2 activation was detected by immunohistochemistry and Western blot analyses.
      The levels of SOD, CAT, GSH, PCO, and MDA were detected in the kidney.
      Immunohistochemistry, Western blot, and real-time PCR analyses were performed to
      evaluate the activation of the nuclear factor kappa B (NF-kappaB) P65 pathway and
      inflammation infiltration in the tubulointerstitium of the rats. RESULTS: Ozone
      therapy improved severe renal insufficiency and tubulointerstitial morphology
      injury as well as restored Nrf2 activation and inhibited the NF-kappaB pathway in
      rats with adenine-induced CKD. Ozone therapy also up-regulated anti-oxidation
      enzymes (SOD, CAT, and GSH) and down-regulated oxidation products (PCO and MDA),
      as well as inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and ICAM-1) in the
      kidney. CONCLUSION: These findings indicated that ozone therapy could attenuate
      tubulointerstitial injury in rats with adenine-induced CKD by mediating Nrf2 and
      NF-kappaB.

PMID- 27872712
TI  - The effect of Quercus brantii gall extract on burn wound healing in rat.
AB  - OBJECTIVES: The aim of the present study was to evaluate the effect of Quercus
      brantii galls extract on the rat skin burn wound healing. MATERIALS AND METHODS:
      Ethanol extract of the galls of Q. brantii was used to treat the induced burn
      wounds on the back of 32 Wistar rats divided into 4 groups. The groups were
      treated by placebo, 1%, 2% and 4% concentration gall extract gels for 14 days and
      the efficacy of treatment was assessed based on reduction of burn wound area, as
      well as histological and molecular characteristics. RESULTS: The mean wound
      surface in the 14th day, in all groups treated by Q. brantii gall extracts were
      larger than control group and the differences were statistically significant
      (P=0.043). The mean histological wound healing scores were not statistically
      different. Analysis of nitric oxide and platelet derived growth factor
      concentration in wound fluids in the 5th day of study showed that there was not
      any significant difference between groups (P=0.468 and 0.312 respectively).
      Fibroblast growth factor (bFGF) concentration in the wound fluids, was
      significantly higher in group treated with 1% gall extract gel in comparison to
      the control group (P=0.026). CONCLUSION: Our results could not prove the
      significant positive effect of Q. brantii galls extract on the burning wound
      healing. More studies with more groups treated with different doses of the Q.
      brantii extract are recommended.

PMID- 27872713
TI  - Expression of pluripotent stem cell markers in mouse uterine tissue during
      estrous cycle.
AB  - It was assumed that uterine stem cells are responsible for the unique
      regenerative capacity of uterine. Therefore, the aim of the present study was to
      investigate the expression of the pluripotent stem cell markers in the mice
      uterine tissue during different stages of estrous cycles. Twelve virgin female
      NMRI mice (6 to 8 weeks old) were considered at proestrus, estrus, metestrus and
      diestrus according to the cell types observed in the vaginal smear and underwent
      hysterectomy operation. Quantitative real-time polymerase chain reaction (PCR)
      and immunohistochemical staining for pluripotent stem cell markers (SOX2, OCT4,
      KLF4, and NANOG) were performed. Immunofluorescence staining revealed that
      expression and localization of the pluripotency markers SOX2, OCT4, KLF4, and
      NANOG at the protein level were not different throughout estrous cycle. Also,
      mRNA of pluripotency markers was detected in all tested samples. However, there
      were no significant differences in their genes expression at each stage and
      during the estrous cycle. Different hormonal profile during the estrous cycle
      could not affect expression of pluripotent stem cell markers in uterine tissue.

PMID- 27872714
TI  - Effects of dietary supplementation of organic acids and phytase on performance
      and intestinal histomorphology of broilers.
AB  - The present experiment was conducted to evaluate the effects of organic acids and
      phytase enzyme supplementation on performance and intestinal histomorphology of
      broilers. The experiment was done in a factorial arrangement 2 * 2 * 2 based on
      completely randomized design with eight treatments, five replicates with 12
      chicks in each until 42 days of age. Diets included natural vinegar (0 and 2%),
      citric acid (CA; 0.00 and 1.00%) and phytase enzyme (PHY; 0.00 and 500 FTU
      phytase per kg of feed). One bird from each treatment replicate was randomly
      selected and slaughtered to evaluate the small intestinal morphology on 42 days
      of age. Analysis of results showed that vinegar increased feed consumption and
      body weight gain in total experimental period (p ? 0.05), while CA significantly
      decreased feed consumption on 0-14 days of age (p ? 0.05). No effect was observed
      on performance in interaction of organic acids together and with PHY group (p >
      0.05). In duodenum CA increased the villus height and width (p ? 0.05) and PHY
      enzyme increased villus width (p ? 0.05) and decreased crypt depth (p ? 0.05). On
      the other hand, CA along with PHY significantly decreased crypt depth (p ? 0.05).
      In jejunum PHY alone and in combination with vinegar increased the goblet cells
      numbers (p ? 0.05), whereas vinegar significantly increased the goblet cells
      numbers in ileum (p ? 0.05). The muscular thickness in duodenum, jejunum, and
      ileum was not affected among different treatment groups. The results showed that
      supplementation of organic acids and phytase together in this experiment, with no
      negative effects on each other, improved their effects on some parameters.

PMID- 27872715
TI  - Molecular characterization of Mycoplasma synoviae isolated from broiler chickens
      of West Azarbaijan province by PCR of vlhA gene.
AB  - Mycoplasma synoviae (MS) is a pathogen responsible for respiratory and locomotor
      disorders and causes major economic losses in poultry industry. Early and
      accurate diagnosis of MS infection plays a major role in control of the
      infection. This study was conducted to characterize Iranian field isolates of MS
      isolated from broiler chickens of West Azarbaijan province (Northwest of Iran),
      and differentiate them from vaccine strain MS-H. Two encoding genes, 16S rRNA and
      vlhA were employed. PCR results using primers related to 16s rRNA and vlhA genes
      were analyzed and compared. Out of 21 field samples, eight samples (38.0%) were
      positive using both sets of primers. Amplified products of vlhA gene were
      sequenced for MS strain identification. The results showed that Iranian field
      isolates of MS had high nucleotide and amino acid similarity. Iranian field
      isolates were distinct from vaccine strain MS-H. Results presented in this study
      showed that characterization of field isolates of MS by sequencing of vlhA gene
      and is beneficial for strain typing and differentiating them from vaccine strain.
      To our knowledge, this is the first study characterizing vlhA gene of MS isolates
      from broiler chickens in the West Azarbaijan province.

PMID- 27872716
TI  - The comparison of digestibility of treated sugarcane tops silage by bacteria or
      whole microorganisms of Holstein cow and buffalo rumen.
AB  - The aim of this study was to evaluate the effects of adding sulfuric acid to
      sugarcane tops silage on rumen bacteria and whole rumen microorganisms (WRM) and
      compare the digestibility of sugarcane tops treated with different amount of
      urea, molasses and sulfuric acid between Holstein cow and Khouzestan buffalo.
      Regardless of the type of the treatment, potential of gas production (B) by cow
      WRM (130.670 mL) was more than buffalo (104.060 mL) (p < 0.05), but the rate of
      gas production (C) by buffalo WRM was greater than cow (0.021 and 0.014 mL per
      hr, respectively) (p < 0.05). The C in treatment containing only 2.40% sulfuric
      acid (0.033 mL per hr) was significantly highest (p < 0.05). Regardless of the
      type of the treatment, the B by cow rumen bacteria (75.040 mL) was more than
      buffalo (67.150 mL), (p < 0.05), while the C by rumen bacteria of buffalo (0.030
      mL per hr) was more than cow (0.017 mL per hr), (p < 0.05). Regardless of the
      type of the animal, the B coefficient of rumen bacteria in treatment only
      containing 2.40% sulfuric acid was higher than control (p < 0.05). Therefore, the
      addition of sulfuric acid not only had no negative effect on microorganisms
      particularly bacteria, but also probably due to present of sulfur in acid, had
      positive effect on nutrients digestibility, and growth of microorganisms. The
      digestibility of sugarcane tops silage treated by cow rumen bacteria and whole
      microorganisms was higher than buffalo.

PMID- 27872717
TI  - The antibacterial effect of Ziziphora clinopodioides essential oil and
      nisinagainst Salmonella typhimurium and Staphylococcus aureus in doogh, a yoghurt
      based Iranian drink.
AB  - Doogh is the most popular and commonly consumed yoghurt-based Iranian drink. The
      aim of this study was to investigate the antibacterial effects of Ziziphora
      clinopodioides essential oil (ZEO) at 0.10 and 0.20% concentrations, nisin at 250
      and 500 IU mL-1, and their combination against Salmonella typhimurium and
      Staphylococcusaureus in doogh during storage at 4 C for  9 days. Nine batches
      were studied as follows: control: no ZEO or nisin added, A: 0.10% ZEO, B: 0.20%
      ZEO, C: 250 IU mL-1 nisin, D: 500 IU mL-1 nisin, E: 0.10% ZEO + 250 IU mL-1
      nisin, F: 0.10% ZEO + 500 IU mL-1 nisin, G: 0.20% ZEO + 250 IU mL-1 nisin and H:
      0.20% ZEO + 500 IU mL-1 nisin. Based on gas-chromatography and mass spectrometry,
      carvacrol (65.22%), thymol (19.51%), p-cymene (4.86%) and gamma-terpinene (4.63%)
      were the major components of ZEO. The populations of S. typhimurium and S.aureus
      in samples treated with all concentrations of the ZEO and nisin were kept below 1
      log CFU mL-1 on day 5 of storage, while the count of S. typhimurium and S.aureus
      was found as 2.72 +/- 0.02 and 2.21 +/- 0.00 log CFU mL-1 on day 5 for untreated
      samples, respectively. The ZEO separately and in combination with nisin, was very
      effective against these two common food-borne pathogens. The ZEO alone and in
      combination with nisin could be considered as a potential strong antimicrobial
      agent that can be used for the growth inhibition of aforementioned bacteria in
      food products especially doogh.

PMID- 27872718
TI  - Histoanatomical study of the lens and ciliary body in ostrich eye.
AB  - In the present study, the lenses and ciliary bodies of 20 ostrich eyes were
      studied macroscopically and microscopically. The histological slides were studied
      after staining by hematoxylin and eosin, Verhoeff, Van Gieson, and periodic acid
      Schiff (PAS). Posterior surface of lens was more convex than its anterior
      surface. The average lens diameter and thickness were respectively measured as
      1.43 +/- 0.00 and 0.85 +/- 0.00 cm. The average ciliary body thickness was
      measured as 1.48 +/- 0.01 cm. In addition, the ciliary body was seen annular with
      mean horizontal and vertical external diameters as 4.80 +/- 0.07 and 4.36 +/-
      0.06 cm, respectively. The retina is extended on ciliary body in this bird. The
      number of ciliary body processes was about 120. The epithelium of lens was
      cuboidal and the lens capsule had intense positive PAS reaction. Also, the
      anterior surface of capsule was thicker than its posterior surface. The lens
      fibers in the central part were thicker than other parts. Elastic and collagen
      fibers were not observed in the lens. The epithelium of ciliary processes had two
      layers; superficial cuboidal non-pigmented layer, and deep heavily pigmented
      layer. The ciliary body was supported by a hyaline cartilage. In addition to the
      smooth muscle fibers, many isolated skeletal muscle fibers were also seen in
      ciliary body. In conclusion, the lens and ciliary body of ostrich were similar to
      other birds, although there were little differences in anatomical dimensions and
      histological characteristics.

PMID- 27872720
TI  - A comparative study on the effects of different cryoprotectants on the quality of
      canine sperm during vitrification process.
AB  - Cryopreservation has the capacity to extend spermatozoa's lifespan and viability.
      In addition, the semen samples can be collected, preserved and stored or sent to
      distant locations and still be used long after the death of the semen donor. In
      this study for the vitrification of dog sperm (fresh and swum-up sperm),
      different cryopreservation mediums on the basis of glycerol, milk and egg yolk
      were used. Then, all of the samples were vitrified in the liquid nitrogen and
      thawed at least 48 hr later for re-examination of sperm parameters. The sperm
      parameters before and after cryopreservation in all groups were compared. It was
      found that during vitrification process, spermatozoa were damaged by the
      mechanical blows in centrifugation during swim-up processing, so they had less
      resistance than fresh semen. The examination of different cryoprotectants
      revealed that milk has better effects on the cryopreservation of semen than
      glycerol and egg yolk. With the comparison of the effects of glycerol and egg
      yolk as cryoprotectants, it was found that glycerol had better effects than egg
      yolk on the cryopreservation of the semen. In conclusion, milk might be used as a
      cryoprotectant instead of glycerol for canine sperm cryopreservation.

PMID- 27872719
TI  - Phylogenetic typing and detection of extended-spectrum beta-lactamases in
      Escherichia coli isolates from broiler chickens in Ahvaz, Iran.
AB  - This study was conducted to reveal the phylogenetic background, to detect the
      genes encoding TEM, SHV and CTX-M-15 extended-spectrum beta-lactamases (ESBL),
      and to analyze their distribution in phylo-groups of 150 Escherichia coli
      isolates from broiler chickens in Ahvaz (Southwest of Iran). Seventy- five
      cloacal swabs from healthy birds (fecal isolates), and 75 heart blood samples
      from birds with colibacillosis (septicemic isolates) were obtained. All isolates
      were phylotyped and screened for ESBL genes by polymerase chain reaction (PCR).
      The fecal isolates belonged to four main phylo-groups, including 41 isolates
      (54.67%) to A, 9 (12.00%) to B1, 5 (6.67%) to B2, and 20 (26.67%) to D. Of
      septicemic isolates, 37 isolates (49.33%) were classified as phylotype A, 5
      (6.67%) as B1, 10 (13.33%) as B2, and 23 (30.67%) as D. In molecular analysis, a
      total of 72 isolates (35 fecal and 37 septicemic) were identified to harbor ESBL
      genes, which were distributed in phylo-groups A, B1, B2, and D. Regardless of the
      type of isolate, blaCTX-M-15 gene was the most common genotype, followed by
      blaTEM and blaSHV genes. This study suggests that broiler chickens in Iran are
      infected to ESBL genes- harboring Escherichia coli strains which may be spread to
      the food chain through fecal contamination of carcasses during slaughtering.

PMID- 27872721
TI  - Prevalence and antibiotic resistance profile of thermophilic Campylobacter spp.
      of slaughtered cattle and sheep in Shiraz, Iran
AB  - Although poultry meat is considered as the main source for human Campylobacter
      infections, there is limited information about non-poultry sources. The present
      study was aimed to investigate the prevalence and the antibiotic resistance of
      thermophilic Campylobacter spp. in fecal samples of the cattle and sheep in
      Shiraz, Iran. A total of 302 fecal samples were obtained from clinically healthy,
      slaughtered cattle and sheep from Shiraz slaughterhouse. The animals were
      clinically healthy before being slaughtered. The samples were cultured according
      to the specific cultivation method under thermophilic conditions. The
      susceptibility of Campylobacter isolates were determined for 13 antimicrobial
      agents. All enriched samples and cultured isolates were targeted for polymerase
      chain reaction (PCR) detection of 16S rRNA and multiplex PCR for determining
      their species. Among 302 fecal samples, 65 (21.5%) and 205 (67.8%) samples were
      positive for the presence of Campylobacter species with the cultivation and PCR
      techniques, respectively. All 65 distinct isolates were susceptible to neomycin
      and colistin and the isolates showed high resistance to cephalotin (83.0%) and
      ciprofloxacin (67.7%). After the multiplex PCR, 78.5% of total positive samples
      showed the simultaneous presence of Campylobacter jejuni and Campylobacter coli.
      In conclusion, the results emphasized that non-poultry farms are important as a
      possible source of Campylobacter infections.

PMID- 27872723
TI  - A human reproductive approach to the study of infertility in chimpanzees: An
      experience at Leon's Zoological Park, Mexico.
AB  - Great apes are mammals close to humans in their genetic, behavioral, social and
      evolutionary characteristics and new genomic information is revolutionizing our
      understanding of evolution in primates. However, all these species are
      endangered. While there are many global programs to protect these species, the
      International Union for Conservation of Nature (IUCN) projects that in a near
      future the wild populations will decrease significantly. Nowadays, the relevance
      of captive populations of great apes is becoming critical for research and
      understanding of pathophysiology of diseases. In this report, the evaluation of
      infertility in a group of captive chimpanzees maintained at Leon's Zoological
      Park using a human infertility protocol is described. Our results suggested that
      infertility in this group was due to low hormonal levels and sperm alterations in
      the male characterized by hormonal assessment and a sperm sample obtained by
      electroejaculation and cryopreserved using human protocols. In the females, it
      was demonstrated that it is possible to follow the follicular cycle using non
      invasive methods based on morphological changes in genitalia, detection of blood
      in urine and measurement of hormones in saliva samples; concluding that fertility
      in females was normal. Also, we demonstrate that human artificial insemination
      procedures may be applied. Our human approach was successful in finding the
      infertility cause in this group of captive chimpanzees. In countries with limited
      resources, collaboration of zoos with human infertility clinics can be beneficial
      for research and management of reproductive aspects of great apes.

PMID- 27872722
TI  - Production of monoclonal antibody against recombinant NS3 protein of bovine viral
      diarrhea virus (NADL strain).
AB  - This study was conducted to investigate the prevalence of subclinical mastitis
      caused by Staphylococcus spp. in ewes in West-Azerbaijan province of Iran.
      Molecular characterization of isolated Staphylococcus spp. from diseased ewes
      were performed using polymerase chain reaction (PCR) followed by restriction
      fragment length polymorphism (RFLP) and DNA sequencing of glyceraldehyde-3
      phosphate dehydrogenase (gap) gene. Also, antibiotic resistance of staphylococcal
      isolates against different antibiotics was investigated. A total number of 900
      milk samples from 450 native ewes in their mid-lactation period were examined by
      the California mastitis test (CMT). The CMT positive samples were cultured and
      bacteria were isolated from 86 (9.50%) glands and 74 (16.40%) ewes. The
      prevalence of subclinical mastitis in the examined ewes was 16.40%.
      Microbiological analysis of milk samples revealed that 27 out of 74 sheep with
      subclinical mastitis were infected with Staphylococcus spp. Amplification of gap
      gene of 27 Staphylococcus isolates generated a single amplicon of 933 bp in size
      confirming that isolates were belonged to Staphylococcus genus. Digestion of PCR
      products by AluI endonuclease generated different RFLP patterns for each species.
      Nucleotide sequencing of gap gene followed by phylogenetic analysis showed that
      the most dominant Staphylococcus species were S. epidermidis, S. xylosus and S.
      chromogenes. Staphylococcal isolates showed the highest resistance to penicillin
      and ampicillin. In conclusion, Staphylococcus species, except for the southern
      parts of the province, play an important role in the development of subclinical
      mastitis in sheep in West-Azerbaijan province of Iran. Also, chloramphenicol,
      ciprofloxacin and neomycin are the most effective antibiotics for treatment of
      this disease.

PMID- 27872724
TI  - Are magnetic resonance imaging or radiographic findings correlated with clinical
      prognosis in spinal cord neuropathy?
AB  - Dogs presented to the Small Animal Hospital of Veterinary Medicine, University of
      Tehran were included in the present study if spinal or intervertebral disc
      involvement was suspected. Clinical signs were recorded as well as general
      information of the patient such as age, breed and sex. Sixty dogs were examined
      radiographically and two standard orthogonal lateral and ventrodorsal projections
      were taken from the suspected region. Then magnetic resonance imaging (MRI) was
      performed for all patients. Agreement between MRI and radiographic findings,
      comparison of sex and breed with diagnostic imaging grades, comparison between
      diagnostic imaging grades and mean age, recovery rate after surgery or medical
      treatment, effects of diagnostic imaging severity grades on surgical or medical
      referrals were evaluated statistically. There were no significant association
      between age, sex and breed and frequency of the intervertebral disk disease.
      Intervertebral disc involvements between L2-L3 and T13-L1 were estimated as the
      most frequent sites of involvements. Sensitivity and specificity of radiography
      were evaluated 90.0% and 46.0%, respectively, by considering the MRI as a gold
      standard modality. There was a significant association between severity of
      disease in the MRI with referral to surgery and medical treatment. The recovery
      rate after surgery was significantly higher than medical treatment. These results
      can be used as a foundation for other studies with more focuses on details of
      injury and larger group of patients.

PMID- 27872725
TI  - A case of monocephalusrachipagus tribrachius tetrapus in a puppy.
AB  - Caudal duplication (dipygus) is an uncommon pathologic of conjoined twinning. The
      conjoined malformation is classified according to the nature and site of the
      union. We report the presence of this malformation in a female crossbreed puppy.
      The puppy was delivered by caesarean section following a prolonged period of
      dystocia. External findings showed a single head (monocephalus) and a normal
      cranium with no fissure in the medial line detected. The thorax displayed a
      caudal duplication arising from the lumbosacral region (rachipagus). The puppy
      had three upper limbs, a right and left, and a third limb in the dorsal region
      where the bifurcation began. The subsequent caudal duplication appeared
      symmetrical. Necropsy revealed internal abnormalities consisting of a complete
      duplication of the urogenital system and a duplication of the large intestines
      arising from a bifurcation of the caudal ileum . Considering the
      morphophysiological description the malformation described would be classified as
      the first case in the dog of a monocephalusrachipagustribrachius tetrapus.

PMID- 27872726
TI  - Reconstruction of long digital extensor tendon by cranial tibial muscle fascia
      graft in a dog.
AB  - Tendon rupture in dogs is generally the result of a direct trauma. This report
      described the use of adjacent muscle autogenic fascial graft for reconstruction
      of distal rupture of long digital extensor tendon in a dog. A two-year-old male
      mix breed dog, was presented with a non-weight bearing lameness of the right hind
      limb and a deep rupture of lateral side of right tarsus. History taking revealed
      that this rupture appeared without any apparent cause, when walking around the
      farm, three days before. Radiography was done and no fracture was observed.
      Hyperextension of right tarsal joint compared to left limb was observed. Under
      general anesthesia, after dissections of the ruptured area, complete rupture of
      long digital extensor tendon was revealed. Then, we attempted to locate the edge
      of the tendon, however, the tendon length was shortened approximately 1 cm.
      Hence, a strip of 1 cm length from fascia of cranial tibial muscle was harvested
      to fill the defect. The graft was sutured to the two ends of tendon using locking
      loop pattern. Subcutaneous layers and the skin were sutured routinely. Ehmer
      sling bandage was applied to prevent weight bearing on the surgical region. Re
      examination and phone contact with the owner eight weeks and six months
      postoperatively revealed a poor lameness and excellent function of the dog,
      respectively. It could be concluded that the fascia of adjacent muscles can be
      used as an autogenic graft for reconstruction of some tendon ruptures.

PMID- 27872728
TI  - What Unrelated Hematopoietic Stem Cell Transplantation in Thalassemia Taught us
      about Transplant Immunogenetics.
AB  - Although the past few decades have shown an improvement in the survival and
      complication-free survival rates in patients with beta-thalassemia major and gene
      therapy is already at an advanced stage of experimentation, hematopoietic stem
      cell transplantation (HSCT) continues to be the only effective and realistic
      approach to the cure of this chronic non-malignant disease. Historically, human
      leukocyte antigen (HLA)-matched siblings have been the preferred source of donor
      cells owing to superior outcomes compared with HSCT from other sources. Nowadays,
      the availability of an international network of voluntary stem cell donor
      registries and cord blood banks has significantly increased the odds of finding a
      suitable HLA matched donor. Stringent immunogenetic criteria for donor selection
      have made it possible to achieve overall survival (OS) and thalassemia-free
      survival (TFS) rates comparable to those of sibling transplants. However, acute
      and chronic graft-versus-host disease (GVHD) remains the most important
      complication in unrelated HSCT in thalassemia, leading to significant rates of
      morbidity and mortality for a chronic non-malignant disease. A careful
      immunogenetic assessment of donors and recipients makes it possible to
      individualize appropriate strategies for its prevention and management. This
      review provides an overview of recent insights about immunogenetic factors
      involved in GVHD, which seem to have a potential role in the outcome of
      transplantation for thalassemia.

PMID- 27872730
TI  - Diagnosis of del(5q) MDS, 14 Years after JAK-2 Positive PV Appearance: Complete
      Remission of both Diseases with Lenalidomide Monotherapy.
AB  - This is the report of the clinical case of a patient who presents the association
      of a JAK-2 positive chronic myeloproliferative neoplasia to a subsequent 5q-
      myelodysplastic syndrome, developed after about 14 years from the first
      diagnosis. Patient's symptoms had rapidly worsened, and she became transfusion
      dependent. Therapy with low-dose Lenalidomide quickly reduced the splenomegaly
      and completely brought white cells counts, haemoglobin, and platelets back to
      normal. After more than one year from the start, blood cell count is still
      normal. As far as we know, this is the first case of an effective treatment with
      Lenalidomide reported in this clinical setting.

PMID- 27872729
TI  - Mild Bleeders: Diagnosis is Elusive in Large Number of Patients.
AB  - BACKGROUND: Bleeding is a common clinical presentation. Even patients with mild
      bleeding disorders are extensively investigated for ascertaining the cause. The
      present study was conducted in order to evaluate the extent of the possibility of
      diagnosis in mild bleeding disorders. MATERIAL AND METHODS: This was a
      prospective study of patients referred for work up of mild bleeding for a period
      of 13 months. A complete blood count, peripheral smear examination, Prothrombin
      time, Partial Thromboplastin time and Thrombin Time, Platelet Aggregometry test,
      tests for von Willebrand's disease and Platelet Factor 3 availability were
      measured. RESULTS: 164 patients presented with mild bleeding, in 114 of the
      patients a single site of bleeding was present. Epistaxis was the most common
      presentation (39%). Cutaneous bleeding (petechiae and purpura) was the next
      common site. History of a major bleeding tendency in the family was present only
      in 11 patients. The investigations showed that VWD (17/164), followed by clotting
      disorders (CD) mainly mild hemophilia (15/164) were the most common diagnosable
      cause. There were also 4 cases of hypofibrinogenemia. The disorders of platelets
      (Platelet function defects/PFD) were the least common (9/164). Rest 123 (75%)
      patients could not be diagnosed on the basis of these investigations and were
      labeled as Bleeding disorders - Unclassified (BDC). CONCLUSION: n our study, 75%
      of the patients with mild bleeding remained undiagnosed even after extensive
      laboratory workup, thus raising a very pertinent question that is it necessary
      that all mild bleeders submit to a broad battery of investigations, as the
      diagnosis continues to be elusive despite extensive workup.

PMID- 27872727
TI  - Identifying High-Risk Chronic Lymphocytic Leukemia: A Pathogenesis-Oriented
      Appraisal of Prognostic and Predictive Factors in Patients Treated with
      Chemotherapy with or without Immunotherapy.
AB  - Chronic lymphocytic leukemia (CLL) displays an extremely variable clinical
      behaviour. Accurate prognostication and prediction of response to treatment are
      important in an era of effective first-line regimens and novel molecules for high
      risk patients. Because a plethora of prognostic biomarkers were identified, but
      few of them were validated by multivariable analysis in comprehensive prospective
      studies, we applied in this survey stringent criteria to select papers from the
      literature in order to identify the most reproducible prognostic/predictive
      markers. Each biomarker was analysed in terms of reproducibility across the
      different studies with respect to its impact on time to first treatment (TTFT),
      progression free survival (PFS), overall survival (OS) and response to treatment.
      We were able to identify the following biomarkers as the most reliable in guiding
      risk stratification in the daily clinical practice: 17p-/TP53 mutations, IGHV
      unmutated configuration, short telomeres and 11q-. However, the method for
      measuring telomere length was not validated yet and 11q- was predictive of
      inferior OS only in those patients who did not receive FCR-like combinations.
      Stage and lymphocytosis were predictive of shorter TTFT and age, high serum
      thymidine kinase levels and poor performance status were predictive of shorter
      OS. Using our criteria no parameter was found to independently predict for
      inferior response to treatment.

PMID- 27872733
TI  - Hyperhemolytic Syndrome Complicating a Delayed Hemolytic Transfusion Reaction due
      to anti-P1 Alloimmunization, in a Pregnant Woman with HbO-Arab/beta-Thalassemia.
AB  - BACKGROUND: Hyperhemolytic Syndrome or Hyperhemolytic Transfusion Reaction
      (HHTR), a life-threatening subset of Delayed Hemolytic Transfusion Reaction
      (DHTR) is characterized by destruction of both transfused and autologous
      erythrocytes evidenced by a fall in post transfusion hemoglobin below the pre
      transfusion level. CASE REPORT: We describe a case of DHTR due to anti-P1
      alloimmunization manifesting with hyperhemolysis in a 30-year-old Greek Pomak
      woman with thalassemia intermedia (HbO-Arab/beta-thalassemia), during the11th
      week of her first gestation. She was successfully managed with avoidance of
      further transfusions and administration of IVIG and corticosteroids. CONCLUSION:
      A high index of suspicion for HHTR is of vital importance among clinicians
      especially since optimal methods for its prevention and treatment remain yet to
      be defined. Early recognition of HHTR leading to prompt cessation of additional
      transfusions and initiation of immunosuppressive treatment can be life-saving,
      especially in clinical settings where limited therapeutic options are available,
      such as in pregnancy.

PMID- 27872734
TI  - Allogeneic Hematopoietic Stem Cell Transplantation for Adult Patients with
      Fanconi Anemia.
AB  - BACKGROUND AND OBJECTIVES: Fanconi anemia (FA) is a rare genetic disorder caused
      by an impaired DNA repair mechanism which leads to an increased tendency toward
      malignancies and progressive bone marrow failure. The only curative management
      available for hematologic abnormalities in FA patients is hematopoietic stem cell
      transplantation (HSCT). This study aimed to report the results of HSCT in adult
      or adolescent FA patients. PATIENTS AND METHODS: Twenty FA patients with ages of
      16 or more who underwent HSCT between 2002 and 2015 enrolled in this study. The
      stem cell source was peripheral blood, and all patients had a full human
      leukocyte antigen (HLA) matched donor, 19 patients had a sibling donor, and one
      had full matched other related. Indications for HSCT were severe bone marrow
      failure or dependence on blood products transfusion and failure of medical
      treatment to sustain peripheral blood elements at an acceptable level. RESULTS:
      Eleven patients were female and 9 male (55% and 45%). Mean age was 24.05 years.
      Mortality rate was 50% (n=10), and the leading cause of death was graft versus
      host disease (GVHD) which occurred in 5 patients (4 cases from acute GVHD and one
      from chronic GVHD). Survival analysis showed an overall 5-year survival of 53.63%
      (95% confidence interval: 29.53%-72.74%) and 13 year survival of 45.96 % (95%
      confidence interval: 22.08%-67.03%) among patients. CONCLUSION: HSCT is the only
      curative management for bone marrow failure in FA patients. But the high rate of
      mortality and morbidity in adolescent and adult patients makes it a challenging
      issue.

PMID- 27872732
TI  - Minimal Residual Disease in Acute Myeloid Leukemia of Adults: Determination,
      Prognostic Impact and Clinical Applications.
AB  - Pretreatment assessment of cytogenetic/genetic signature of acute myeloid
      leukemia (AML) has been consistently shown to play a major prognostic role but
      also to fail at predicting outcome on individual basis, even in low-risk AML.
      Therefore, we are in need of further accurate methods to refine the patients'
      risk allocation process, distinguishing more adequately those who are likely to
      recur from those who are not. In this view, there is now evidence that the
      submicroscopic amounts of leukemic cells (called minimal residual disease, MRD),
      measured during the course of treatment, indicate the quality of response to
      therapy. Therefore, MRD might serve as an independent, additional biomarker to
      help to identify patients at higher risk of relapse. Detection of MRD requires
      the use of highly sensitive ancillary techniques, such as polymerase chain
      reaction (PCR) and multiparametric flow cytometry(MPFC). In the present
      manuscript, we will review the current approaches to investigate MRD and its
      clinical applications in AML management.

PMID- 27872731
TI  - Infectious Complications after Umbilical Cord-Blood Transplantation from
      Unrelated Donors.
AB  - Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells
      for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared
      with other stem cell sources from adult donors, it has the advantages of
      immediate availability of cells, absence of risk to the donor and reduced risk of
      graft-versus-host disease despite donor-recipient HLA disparity. However, the use
      of UCB is limited by the delayed post-transplant hematologic recovery due, at
      least in part, to the reduced number of hematopoietic cells in the graft and the
      delayed or incomplete immune reconstitution. As a result, severe infectious
      complications continue to be a leading cause of morbidity and mortality following
      UCB transplantation (UCBT). We will address the complex differences in the immune
      properties of UCB and review the incidence, characteristics, risk factors, and
      severity of bacterial, fungal and viral infectious complications in patients
      undergoing UCBT.

PMID- 27872735
TI  - Fetal Hemoglobin Modifies the Disease Manifestation of Severe Plasmodium
      Falciparum Malaria in Adult Patients with Sickle Cell Anemia.

PMID- 27872736
TI  - Zika Virus: a Review from the Virus Basics to Proposed Management Strategies.
AB  - This review aims to summarize the body of knowledge available on Zika virus to
      date. A comprehensive review of the scientific literature on Zika virus was
      performed with the aim to stress relevant aspects for healthcare professionals in
      the non-endemic areas. For several years, the Zika virus infection was considered
      an extremely rare exotic disease with poor clinical relevance. However, Zika
      virus has recently gained the attention of the scientific community and public
      opinion since the virus spread to the Pacific islands and the South America in an
      unprecedented epidemic, and additionally due to the definitive evidence that the
      infection could be complicated by Guillain-Barre syndrome, passed through
      vertical transmission, and result in central nervous system abnormalities
      (including microcephaly) of the fetus. Studies and scientific evidence on the
      complications associated with Zika virus infection are growing day by day. It is
      advisable that the healthcare professionals working in non-endemic areas maintain
      full awareness on this issue in order to practice proper management of the
      imported cases of Zika virus infection.

PMID- 27872739
TI  - 30 Years Retrospective Review of Tuberculosis Cases in a Tuberculosis Dispensary
      in Bursa/Nilufer, Turkey (1985-2014): Changes of Epidemics.
AB  - OBJECTIVE: The aim of this study is to describe the epidemiological and clinical
      aspects of patients who applied to the Bursa Nilufer Tuberculosis Dispensary by
      investigating the trends in epidemics over three decades. METHOD: In this
      retrospective observational study, the records of all tuberculosis cases (1630
      patients) treated in the last 30 years (1985-2014) at the Bursa Nilufer
      Tuberculosis Dispensary were examined and statistically analyzed. RESULTS: Males
      comprised 65.2% of the patients. The ages of the patients ranged from 1 to 87
      years, and the mean age was 37.4 (95% CI: 36.6-38.2). Among the cases, 86.7% were
      new infections and 74.1% were pulmonary tuberculosis. In the last decade, the
      education level, the percentage of patients who had received a BCG vaccination,
      the proportion of women and active employees among them increased (p<0.05), while
      it decreased among men (p<0.05). Clinical symptoms accompanying TB such as
      weakness, anorexia, weight loss, and cough, decreased to a statistically
      significant degree (p<0.05). In the last decade, the mortality rate was 3.6% and
      increased compared with previous decades (p<0.05). Mortality was higher among
      patients who were elderly, male, did not have a BCG scar or had a chronic disease
      (p<0.05). CONCLUSION: This study adds information about the change of TB
      epidemics in Turkey in the last 30 years. Further studies are needed to determine
      the risk factors associated with tuberculosis mortality and to evaluate the
      effectiveness control programs of this disease.

PMID- 27872738
TI  - The ICET-A Recommendations for the Diagnosis and Management of Disturbances of
      Glucose Homeostasis in Thalassemia Major Patients.
AB  - Iron overload in patients with thalassemia major (TM) affects glucose regulation
      and is mediated by several mechanisms. The pathogenesis of glycaemic
      abnormalities in TM is complex and multifactorial. It has been predominantly
      attributed to a combination of reduced insulin secretory capacity and insulin
      resistance. The exact mechanisms responsible for progression from norm glycaemia
      to overt diabetes in these patients are still poorly understood but are
      attributed mainly to insulin deficiency resulting from the toxic effects of iron
      deposited in the pancreas and insulin resistance. A group of endocrinologists,
      haematologists and paediatricians, members of the International Network of
      Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A)
      convened to formulate recommendations for the diagnosis and management of
      abnormalities of glucose homeostasis in thalassemia major patients on the basis
      of available evidence from clinical and laboratory data and consensus practice.
      The results of their work and discussions are described in this article.

PMID- 27872740
TI  - Follicular Lymphoma: A Clinicopathological Analysis from a Tertiary Care
      Institute in Southern India.
AB  - INTRODUCTION: Follicular lymphoma (FL) is an indolent lymphoproliferative
      disorder of B-cells with variable clinical behavior. It is the second most common
      subtype of Non-Hodgkin lymphoma in western countries but reported to have a lower
      incidence in Asia. MATERIALS AND METHODS: Cases of FL diagnosed in the Department
      of Pathology of our Institute from January 2009 to June 2015 were included in the
      study. The clinicopathological parameters including staging, histological
      details, and immunohistochemical markers CD20, CD10 and BCL-2 were recorded in
      all the cases. RESULTS: Of the 497 cases of Non-Hodgkin Lymphoma reported during
      the study period, 36 (7.2%) cases were follicular lymphoma. The mean age was 50
      years with male to female ratio of 3.2:1. Grade 1/2 was seen in 70% cases. 22 %
      cases had low grade with high proliferation index (Ki67 > 40%). Granulomatous
      response was seen in two cases. Diffuse large cell lymphoma component was present
      in four cases. Bone marrow involvement and peripheral blood spill were seen in 12
      (37.5%) and six cases (18.8%) respectively. 72% cases were in stage 3 or 4.
      CONCLUSION: The incidence of FL was lower in our study than other Indian studies.
      FL presented in the elderly, with male predominance and disseminated stage. The
      study highlights features of low grade with high proliferation index,
      granulomatous response, leukemic involvement, and transformation to high grade
      lymphoma.

PMID- 27872741
TI  - Novel Drugs in Follicular Lymphoma.
AB  - Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and
      constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease
      is characterized by recurrent relapses and progressively shorter remissions with
      a median survival of 10yrs. The impossibility of achieving a definite cure, have
      prompted investigations into the possible role of more active and less toxic
      strategies with innovative therapeutic agents. Recently Casulo et al.
      demonstrated that approximately 20% of patients with FL relapse within two years
      after achieving remission with R-CHOP and have a poor prognosis. It is
      conceivable that this particularly chemoresistant population would benefit from
      specifically targeting the biologic and genetic factors that likely contribute to
      their poor prognosis. Evolving strategies for difficult to treat FL patients have
      recently considered immunomodulatory agents, new monoclonal antibodies as well as
      drugs targeting selective intracellular pathways. The importance of targeting the
      microenvironment together with the malignant FL cell has been particularly
      underscored. We review the most promising approaches, such as combining anti-CD20
      antibodies with immunomodulatory drugs (Lenalidomide), mAbs directed against
      other surface antigens such as CD22 and CD23 (Epratuzumab, Lumiliximab),
      immunomodulatory antibodies such as PD-1, or inhibitors of key steps in the B
      cell receptor pathway signaling such as PI3K inhibitors (Idelalisib, Duvelisib).
      Another highly attractive approach is the application of the bi-specific T-cell
      engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens.
      Moreover, we highlight the potential of these therapies, taking into account
      their toxicity. Of course, we must wait for Phase III trials results to confirm
      the benefit of these new treatment strategies toward a new era of chemotherapy
      free treatment for follicular lymphoma.

PMID- 27872737
TI  - Immunity to Infections after Haploidentical Hematopoietic Stem Cell
      Transplantation.
AB  - The advantage of using a Human Leukocyte Antigen (HLA)-mismatched related donor
      is that almost every patient who does not have an HLA-identical donor or who
      urgently needs hematopoietic stem cell transplantation (HSCT) has at least one
      family member with whom shares one haplotype (haploidentical) and who is promptly
      available as a donor. The major challenge of haplo-HSCT is intense bi-directional
      alloreactivity leading to high incidences of graft rejection and graft-versus
      host disease (GVHD). Advances in graft processing and pharmacologic prophylaxis
      of GVHD have reduced these risks and have made haplo-HSCT a viable alternative
      for patients lacking a matched donor. Indeed, the haplo-HSCT has spread to
      centers worldwide even though some centers have preferred an approach based on T
      cell depletion of G-CSF-mobilized peripheral blood progenitor cells (PBPCs),
      others have focused on new strategies for GvHD prevention, such as G-CSF priming
      of bone marrow and robust post-transplant immune suppression or post-transplant
      cyclophosphamide (PTCY). Today, the graft can be a megadose of T-cell depleted
      PBPCs or a standard dose of unmanipulated bone marrow and/or PBPCs. Although
      haplo-HSCT modalities are based mainly on high intensity conditioning regimens,
      recently introduced reduced intensity regimens (RIC) showed promise in decreasing
      early transplant-related mortality (TRM), and extending the opportunity of HSCT
      to an elderly population with more comorbidities. Infections are still mostly
      responsible for toxicity and non-relapse mortality due to prolonged
      immunosuppression related, or not, to GVHD. Future challenges lie in determining
      the safest preparative conditioning regimen, minimizing GvHD and promoting rapid
      and more robust immune reconstitution.

PMID- 27872743
TI  - The Slopes Remain the Same: Reply to Wolfe (2016).
AB  - Wolfe (2016) responds to my article (Kristjansson, 2015), arguing among other
      things, that the differences in slope by response method in my data reflect speed
      accuracy trade-offs. But when reaction times and errors are combined in one score
      (inverse efficiency) to sidestep speed accuracy trade-offs, slope differences
      still remain. The problem that slopes, which are thought to measure search speed,
      differ by response type therefore remains.

PMID- 27872744
TI  - Association between sports type and overuse injuries of extremities in children
      and adolescents: a systematic review.
AB  - BACKGROUND: Sporting activities can cause injuries and overuse injuries of the
      extremities (OIE) in children have been shown to be more common than injuries
      caused by trauma. The lower extremity is more frequently affected than the upper
      extremity in OIE, but it is not known whether injury site and diagnosis vary in
      different sporting activities. PURPOSE: To identify any differences between
      sports in relation to diagnoses and anatomical areas most likely to be injured.
      METHODS: A search was made in November 2014 and again in June 2016 in PubMed,
      SportDiscus, PsycInfo and Web of Sciences. Search terms were: " overuse injuries
      OR cumulative trauma disorders OR musculoskeletal injuries " AND " extremity OR
      limb " AND " physical activity OR sport OR risk factor OR predictors OR exercises
      " AND " child OR adolescent OR young adults ". Inclusion criteria were: 1)
      prospective, retrospective, or cross-sectional study design; 2) age <=19 years;
      3) the articles must clearly state if reported cases were classified as traumatic
      or overuse injuries; 4) reporting on OIE in relation to a particular sports type,
      and 5) sample size >50. A blinded systematic review was conducted. RESULTS: In
      all, nine of the 736 identified articles were included, studying soccer,
      handball, orienteering, running, dance, and gymnastics. The incidence of OIE was
      given only in a few articles but at least the site and diagnosis of OIE were
      identifiable. The lower limb is more often affected than the upper in all sports
      covered, and, in general, the lower leg and knee are the two most often affected
      areas. However, in handball, the elbow was the second most often reported area,
      and in gymnastics injuries of the foot appeared to be more frequent than in the
      other sports. No differences in diagnoses were observed between sports types.
      CONCLUSION: Our work contributes new information, namely that the site of OIE in
      children and adolescents appears to vary only somewhat between different types of
      sports. Further well-designed surveillance studies are needed to improve
      knowledge that can help prevent injuries in children and adolescents
      participating in sports activities.

PMID- 27872742
TI  - Systemic Front Line Therapy of Follicular Lymphoma: When, to Whom and How.
AB  - The natural history of follicular lymphoma is usually characterized by an
      indolent course with a high response rate to the first line therapy followed by
      recurrent relapses, with a time to next treatment becoming shorter after each
      subsequent treatment line. More than 80% of patients have advanced stage disease
      at diagnosis. The time of initiation and the nature of the treatment is mainly
      conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and
      patients preference. A number of clinical and biological factors have been
      determined to be prognostic in this disease, but the majority of them could not
      show to be predictive of response to treatment, and therefore can't be used to
      guide the treatment choice. CD20 expression is the only predictive factor
      recognized in the treatment of FL and justifies the use of "naked" or
      "conjugated" anti-CD20 monoclonal antibodies as a single agent or in combination
      with chemo- or targeted therapy. Nevertheless, as this marker is almost
      universally found in FL, it has little role in the choice of treatment. The
      outcome of patients with FL improved significantly in the last years, mainly due
      to the widespread use of rituximab, autologous and allogeneic transplantation in
      young and fit relapsed patients, the introduction of new drugs and the
      improvement in diagnostic accuracy and management of side effects. Agents as new
      monoclonal antibodies, immuno-modulating drugs, and target therapy have recently
      been developed and approved for the relapsed setting, while studies to evaluate
      their role in first line treatment are still ongoing. Here we report our
      considerations on first line treatment approach and on the potential factors
      which could help in the choice of therapy.

PMID- 27872745
TI  - Critical review of sham surgery clinical trials: Confounding factors analysis.
AB  - OBJECTIVE: Sham surgery (placebo surgery) is an intervention that omits the step
      thought to be therapeutically necessary. In surgical clinical trials, sham
      surgery serves an analogous purpose to placebo drugs, neutralizing biases such as
      the placebo effect. A critical review was performed to study the statistical
      relevance of the clinical trials about sham surgery in the light of potential
      confounding factors. MATERIALS AND METHODS: For the critical review 52 articles
      were included. The possible confounding factors have been studied using a
      structured interpretative research form designed by the authors. This form
      includes the following ten confounding factors: I), lack of homogeneity among
      inclusion/exclusion criteria. II), false double blind. III), lack of post-surgery
      double blind. IV), power of the study. V), sample characteristics. VI), lost
      patients to Follow-up. VII), gender distribution. VIII), age equilibrium. IX),
      lack of psychological patient evaluation. X), lack of psychiatric patient
      evaluation. In most of the studies, at least one confounding factor was present.
      RESULTS: The analysis of the confounding factors showed that they could influence
      the reliability of the surgical placebo effects. CONCLUSIONS: The validity of
      sham surgery should be reconsidered.

PMID- 27872746
TI  - A prospective cohort study to assess the role of FDG-PET in differentiating
      benign and malignant follicular neoplasms.
AB  - BACKGROUND: Follicular and Hurthle cell neoplasms are diagnostic challenges. This
      prospective study was designed to evaluate the efficacy of [18F]-2-fluoro-2-deoxy
      d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) in
      predicting the risk of malignancy in follicular/Hurthle cell neoplasms. MATERIALS
      AND METHODS: Fifty thyroid nodules showing follicular/Hurthle cell neoplasm on
      prior ultrasonography guided fine needle aspiration cytology (FNAC) were
      recruited into this study. A FDG-PET/CT scan, performed for neck and superior
      mediastinum, was reported by a single observer, blinded to the surgical and
      pathology findings. Receiver operating characteristic (ROC) curve analysis of
      maximum standardized uptake value (SUVmax) and the area under the curve (AUROC)
      were used to assess discrimination between benign from malignant nodules. Youden
      index was used to identify the optimal cut-off SUVmax for diagnosing malignancy.
      Sensitivity, specificity, predictive values and overall accuracy were used as
      measures of performance. RESULTS: Our study group comprises of 31 benign and 19
      malignant thyroid nodules. After excluding all Hurthle cell adenomas, the AUROC
      for discriminating benign and malignant non-Hurthle cell neoplasms was 0.79 (95%
      CI, 0.64-0.94; p = 0.001); with SUVmax of 3.25 as the best cut-off for the
      purpose. PET/CT had sensitivity of 79% (95% CI, 54-93%), specificity of 83% (95%
      CI, 60-94%), positive predictive value (PPV) of 79% (95% CI, 54-93%), and
      negative predictive value (NPV) of 83% (95% CI, 60-94%). The overall accuracy was
      81%. CONCLUSIONS: FDG-PET/CT can help in differentiating benign and malignant non
      Hurthle cell neoplasms. SUVmax of 3.25 was found to be the best for identifying
      malignant non-Hurthle cell follicular neoplasms.

PMID- 27872747
TI  - Promoting public health through nutrition labeling - a study in Brazil.
AB  - BACKGROUND: Food and nutrition education allows individuals to build knowledge
      and values, reframe their food practices, and develop strategies for a healthy
      diet. Food choices within the diet represent a determinant of individual health
      status. Regardless of the food quality, the consumption of calorie-dense foods
      does not promote better health conditions for the population and can worsen
      emerging health problems. The present study aimed to describe and analyze the
      effectiveness of educational activities related to nutrition information for
      enabling healthy food choices, as a tool to promote public health. METHODS: To
      describe and analyze the effectiveness of an educational intervention regarding
      nutrition labeling as a tool to promote healthy food choices, 702 individuals
      were enrolled in the present quasi-experimental study. The Wilcoxon and McNemar
      tests were used to compare the pre- and post-intervention data, and a p value
      <0.05 was considered statistically significant. RESULTS: Of the 702 participants
      (mean age, 26.6 years), 17.4 % were male, and 82.6 % were female. The education
      level was high school for 53.2 % of the participants. The mean income was R$
      1969.54 (about 500 USD). In the pre-test, 55.8 % of the respondents reported
      consulting the nutrition information provided on packaged foods. At the post
      test, 72.0 % of respondents reported consulting this information (p < 0.001;
      Table 1). However, the change in the response regarding the purchase of packaged
      products was borderline significant. CONCLUSIONS: The results indicate that the
      intervention was feasible and acceptable and improved knowledge regarding the
      role of nutrition labeling in promoting healthy eating. These results support the
      importance of an educational intervention to reinforce healthy food choices.

PMID- 27872748
TI  - Hemothorax following lung transplantation: incidence, risk factors, and effect on
      morbidity and mortality.
AB  - BACKGROUND: Hemothorax after lung transplantation may result in increased post
      operative morbidity and mortality. Risk factors for developing hemothorax and the
      outcomes of patients who develop hemothorax have not been well studied. METHODS:
      A retrospective chart review was performed on all patients who underwent lung
      transplantation at a single center between March 2009 and July 2014. Comparison
      was made between patients with and without hemothorax post-transplant. RESULTS:
      There were 132 lung transplantations performed during the study period.
      Hemothorax was a complication in 17 (12.9 %) patients, occurring an average of 9
      days after transplant. No difference was found between the hemothorax and non
      hemothorax groups with respect to age, preoperative anticoagulation, lung
      allocation score, prior thoracotomy, coagulation profile, use of cardiopulmonary
      bypass, ischemic time, or postoperative P/F ratio. There was a trend towards a
      higher incidence of hemothorax in patients with underlying sarcoidosis and re
      transplantation (p = 0.13 and 0.17, respectively). Hemothorax developed early
      (<48 h post-operatively) in 5 patients and presented in a delayed manner (>=48 h
      post-operatively) in 12 patients. Delayed hemothorax occurred primarily in the
      setting of anticoagulation (10 out of 12 patients). The hemothorax group had
      decreased ventilator-free days (p = 0.006), increased ICU length of stay (p =
      0.01) and increased hospital length of stay (p = 0.005). Hemothorax was also
      associated with reduced 90-day survival (p = 0.001), but similar 1, 3, and 5-year
      survival (p = 0.63, p = 0.30, and p = 0.25), respectively). CONCLUSION: The
      development of hemothorax is associated with increased morbidity and decreased
      short-term survival. Hemothorax may present either within the first 48 h after
      surgery or in a delayed fashion, most commonly in the setting of anticoagulation.

PMID- 27872749
TI  - "Vaginella massiliensis" gen. nov., sp. nov., a new genus cultivated from human
      female genital tract.
AB  - We relate the main characteristics of "Vaginella massiliensis" strain Marseille
      P2517 (= DSM 102346 = CSUR P2517), a new member of the Flavobacteriaceae family.
      The strain Marseille P2517 was cultivated from a vaginal swab from a healthy 22
      year-old woman.

PMID- 27872750
TI  - "Corynebacterium urinapleomorphum" sp. nov., isolated from a urine sample of a 2
      month-old boy affected by rotavirus gastroenteritis.
AB  - We report the main characteristics of "Corynebacterium urinapleomorphum" strain
      Marseille-P2799T (CSURP2799), isolated from a urine sample from a 2-month-old boy
      with rotavirus gastroenteritis.

PMID- 27872751
TI  - Novel gene (TMEM230) linked to Parkinson's disease.
AB  - Mutations in six genes are known to cause Parkinson's disease (PD) (autosomal
      dominant: alpha-synuclein, LRRK2, VPS35 and autosomal recessive: Parkin, PINK1
      and DJ1) and number of other genes are implicated. In a recent article Deng and
      colleagues studied a large four generation American family of European descent
      and linked mutations in a novel gene, transmembrane-protein 230 gene (TMEM230)
      with lewy body confirmed PD. The authors demonstrated that pathogenic TMEM230
      variants in primary mouse neurons affected movement of synaptic vesicles
      suggesting that TMEM230 may slow vesicular transport. Further experiments in
      HEK293 cells (carrying the pathogenic TMEM230 variants) showed increased alpha
      synuclein levels. This study indicated that the impaired vesicular trafficking
      may contribute to the pathogenesis of PD. Understanding the various cellular
      mechanisms leading to PD may lead to the development of novel, much needed
      therapeutic options. These mechanisms could include: enhanced clearance of
      damaged mitochondria, development of kinase inhibitors, VPS35/retromer function
      enhancers or now the possibility of vesicular transport modification.

PMID- 27872752
TI  - In-vitro toxicity study of poly(alkylphenol) as vulcanizing agent.
AB  - In this study, cytotoxicity of various novel poly(alkylpehnol) derivatives which,
      one of constituent for vulcanizing agent, could be adjusted in medical elastic
      rubber applications were investigated under various conditions of cytotoxicity
      test. By MTT-assay which according to ISO 10993-5 regulation, we could figure out
      cell viability of mouse fibroblast in various sample conditions. Furthermore, by
      Live & Dead Cell assay, we could get colorimetric cell viability via fluorescence
      images.

PMID- 27872754
TI  - Evaluation of Contrast Sensitivity, Chromatic Vision, and Reading Ability in
      Patients with Primary Open Angle Glaucoma.
AB  - Purpose. To compare contrast sensitivity, acquired color vision deficiency, and
      reading ability in patients with glaucoma at different stages of the disease and
      to establish correlations between visual field parameters and visual function
      scores. Methods. This prospective cross-sectional study included 121 glaucoma
      patients. Subjects with a diagnosis of chronic open angle glaucoma were recruited
      and classified according to Hodapp-Parrish-Anderson criteria. Patients with
      severe visual field defects were excluded because they were older, which could
      bias the interpretation of visual function tests. Contrast sensitivity was
      measured using the Pelli-Robson Chart and the CSV1000E test. Chromatic vision was
      evaluated using the Farnsworth-panel D15 and the L'Anthony D15 tests of Vision
      Color Recorder software. Reading ability was measured using Radner-Vissum test.
      Results. Contrast sensitivity (with photopic and mesopic luminance with glare)
      differed significantly between patients with early and moderate visual field
      defects (p < 0.05). Reading ability scores and results of the chromatic vision
      tests did not differ significantly between the two groups. Significant and
      moderate Spearman correlations between visual field indexes and contrast
      sensitivity tests were detected. Conclusions. Contrast sensitivity was
      significantly worse in patients with moderate glaucoma compared to those with
      early-stage glaucoma. Evaluation of visual function in clinical practice provides
      important information to address a glaucoma patient's vision complaints.

PMID- 27872753
TI  - Multifunctional Thioredoxin-Like Protein from the Gastrointestinal Parasitic
      Nematodes Strongyloides ratti and Trichuris suis Affects Mucosal Homeostasis.
AB  - The cellular redox state is important for the regulation of multiple functions
      and is essential for the maintenance of cellular homeostasis and antioxidant
      defense. In the excretory/secretory (E/S) products of Strongyloides ratti and
      Trichuris suis sequences for thioredoxin (Trx) and Trx-like protein (Trx-lp) were
      identified. To characterize the antioxidant Trx-lp and its interaction with the
      parasite's mucosal habitat, S. ratti and T. suis Trx-lps were cloned and
      recombinantly expressed. The primary antioxidative activity was assured by
      reduction of insulin and IgM. Further analysis applying an in vitro mucosal 3D
      cell culture model revealed that the secreted Trx-lps were able to bind to
      monocytic and intestinal epithelial cells and induce the time-dependent release
      of cytokines such as TNF-alpha, IL-22, and TSLP. In addition, the redox proteins
      also possessed chemotactic activity for monocytic THP-1 cells and fostered
      epithelial wound healing activity. These results confirm that the parasite
      secreted Trx-lps are multifunctional proteins that can affect the host intestinal
      mucosa.

PMID- 27872755
TI  - Changes in Anterior Segment Morphology of Iris Bombe before and after Laser
      Peripheral Iridotomy in Patients with Uveitic Secondary Glaucoma.
AB  - Purpose. To quantify changes in anterior segment (AS) parameters after laser
      peripheral iridotomy (LPI) using AS-optical coherence tomography (OCT) of iris
      bombe. Method. AS images of eight eyes were captured before and after iris bombe
      and more than 2 weeks after LPI (post-LPI) using AS-OCT. We compared the
      following AS parameters: anterior chamber depth (ACD), anterior chamber volume
      (ACV), iris curvature (IC), iris thickness at 500 MUm from the scleral spur (IT
      1) in the middle between the iris root and pupillary margin (IT-2) and 500 MUm
      from the pupillary margin (IT-3) to the anterior chamber angle (ACA) (angle
      opening distance [AOD750]), and trabecular iris space area. Results. Mean IT-1
      and IT-3, but not IT-2, were lower after iris bombe (IT-1, P = 0.001; IT-2, P =
      0.081; and IT-3, P = 0.001). There were no significant differences between ACD at
      pre-LPI and before iris bombe (P = 0.096). The mean ACV and AOD750 of iris bombe
      increased at post-LPI (ACV, P < 0.01, and AOD750, P < 0.05). The mean IT-1, IT-2,
      and IT-3 increased at post-LPI (all, P <= 0.01). IC decreased at post-LPI (P <
      0.001), and ACD at post-LPI did not change. Conclusions. The iris extends and
      becomes thinner during iris bombe. LPI during bombe decreases the IC and
      increases the ACV and ACA.

PMID- 27872757
TI  - Sports Nutrition Knowledge among Mid-Major Division I University Student
      Athletes.
AB  - Competitive athletes have goals to optimize performance and to maintain healthy
      body composition. Sports nutrition is a component of training programs often
      overlooked by student-athletes and their coaches. The purpose of this study was
      to examine student-athletes' sports nutrition knowledge across sex, class level,
      team, and completion of prior nutrition coursework. Participants included 123 mid
      major Division I university student-athletes (47 females and 76 males) from
      baseball, softball, men's soccer, track and field, and tennis. The student
      athletes completed a survey questionnaire to determine adequate sports nutrition
      knowledge (mean >= 75%). The overall mean sports nutrition knowledge score for
      the student-athletes was 56.9% which was considered inadequate sports nutrition
      knowledge (mean < 75%). Only 12 student-athletes achieved adequate sports
      nutrition knowledge score of 75% or higher. There were no differences by sex,
      class level, team, and completion of prior nutrition coursework. Student
      athletes' inadequate sports nutrition knowledge may place them at nutrition risk,
      lead to impaired performance, and affect their lean body mass and energy levels.
      Athletics personnel should not assume student-athletes have adequate sports
      nutrition knowledge. Athletic departments may make available a board certified
      Sports Dietitian or Registered Dietitian and offer classroom or online courses
      facilitating student-athletes to optimize nutrition knowledge and behaviors.

PMID- 27872756
TI  - Prevalence of Hypertension and Its Associated Risk Factors among 34,111 HAART
      Naive HIV-Infected Adults in Dar es Salaam, Tanzania.
AB  - Background. Elevated blood pressure has been reported among treatment naive HIV
      infected patients. We investigated prevalence of hypertension and its associated
      risk factors in a HAART naive HIV-infected population in Dar es Salaam, Tanzania.
      Methods. A cross-sectional analysis was conducted among HAART naive HIV-infected
      patients. Hypertension was defined as systolic blood pressure (SBP) >= 140 mmHg
      and/or diastolic blood pressure (DBP) >= 90 mmHg. Overweight and obesity were
      defined as body mass index (BMI) between 25.0-29.9 kg/m2 and >=30 kg/m2,
      respectively. We used relative risks to examine factors associated with
      hypertension. Results. Prevalence of hypertension was found to be 12.5%. After
      adjusting for possible confounders, risk of hypertension was 10% more in male
      than female patients. Patients aged >=50 years had more than 2-fold increased
      risk for hypertension compared to 30-39-years-old patients. Overweight and
      obesity were associated with 51% and 94% increased risk for hypertension compared
      to normal weight patients. Low CD4+ T-cell count, advanced WHO clinical disease
      stage, and history of TB were associated with 10%, 42%, and 14% decreased risk
      for hypertension. Conclusions. Older age, male gender, and overweight/obesity
      were associated with hypertension. Immune suppression and history of TB were
      associated with lower risk for hypertension. HIV treatment programs should screen
      and manage hypertension even in HAART naive individuals.

PMID- 27872758
TI  - Thrombosis of iliac vessels, a rare complication of endometriosis: Case report
      and review of literature.
AB  - A young women presented with iliac vein thrombosis, as extrapelvic endometriosis
      complication. Endometriosis mass had a subfascial position at the level of
      external oblique muscle and extended to the iliac vein. This paper reviewed the
      literature on endometriosis cases localized into striated muscles and cases of
      deep vein thrombosis due to this disease. There are not similar cases in the
      literature. The diagnostic role of ultrasound, in obtaining the definitive
      histological diagnosis, may be further enhanced through Elasticity Imaging
      Techniques and ultrasound-guided biopsy.

PMID- 27872759
TI  - Impact of moderate intensity aerobic exercise on chemotherapy-induced anemia in
      elderly women with breast cancer: A randomized controlled clinical trial.
AB  - Exercises are often recommended for patients suffering from anemia to improve
      physical conditioning and hematologic parameters. Hence, the present study aimed
      to investigate the impact of moderate intensity aerobic exercise on chemotherapy
      induced anemia. Thirty elderly women with breast cancer underwent chemotherapy
      and were randomly assigned into two equal groups; Group A received aerobic
      exercise for 25-40 min at 50-70% of the maximum heart rate, 3 times/week for 12
      weeks in addition to usual daily living activities, medication and nutritional
      support. Group B who did not train served as controls. Hemoglobin (Hb), and red
      blood cell count (RBCs) were evaluated pre-treatment and after 12 weeks of
      training. There were significant declines of both Hb (t = 16.30; P < 0.001) and
      RBCs (t = 10.38; P < 0.001) in group B relative to group A. Regarding group A, Hb
      increased from 11.52 +/- 0.62 to 12.10 +/- 0.59 g/dL with a 5.03% change, while
      RBCs increased from 4.24 +/- 0.37 to 4.49 +/- 0.42 million cells/MUL with a 5.89%
      change. Between-group differences were noteworthy regarding Hb (t = -5.34; P <
      0.001) and RBCs (t = -5.314; P < 0.001). The results indicate that regular
      participation in moderate intensity aerobic exercise can enhance chemotherapy
      induced anemia.

PMID- 27872760
TI  - Factors Associated with PMTCT Cascade Completion in Four African Countries.
AB  - Background. Many countries are working to reduce or eliminate mother-to-child
      transmission (MTCT) of HIV. Prevention efforts have been conceptualized as steps
      in a cascade but cascade completion rates during and after pregnancy are low.
      Methods. A cross-sectional survey was performed across 26 communities in
      Cameroon, Cote d'Ivoire, South Africa, and Zambia. Women who reported a pregnancy
      within two years were enrolled. Participant responses were used to construct the
      PMTCT cascade with all of the following steps required for completion: at least
      one antenatal visit, HIV testing performed, HIV testing result received,
      initiation of maternal prophylaxis, and initiation of infant prophylaxis. Factors
      associated with cascade completion were identified using multivariable logistic
      regression modeling. Results. Of 976 HIV-infected women, only 355 (36.4%)
      completed the PMTCT cascade. Although most women (69.2%) did not know their
      partner's HIV status; awareness of partner HIV status was associated with cascade
      completion (aOR 1.4, 95% CI 1.01-2.0). Completion was also associated with
      receiving an HIV diagnosis prior to pregnancy compared with HIV diagnosis during
      or after pregnancy (aOR 14.1, 95% CI 5.2-38.6). Conclusions. Pregnant women with
      HIV infection in Africa who were aware of their partner's HIV status and who were
      diagnosed with HIV before pregnancy were more likely to complete the PMTCT
      cascade.

PMID- 27872761
TI  - Effective Concentration of Lidocaine Plus Fentanyl for Caudal Block in Patients
      Undergoing Transrectal Ultrasound Guided Prostate Biopsy.
AB  - Objective. This study determined the effective concentration (EC) of lidocaine
      plus 75 MUg fentanyl for caudal block in patients undergoing transrectal
      ultrasound (TRUS) guided prostate biopsy. Methods. Consecutive male patients
      scheduled for TRUS guided prostate biopsy were enrolled. The mixed solution for
      caudal block contained lidocaine and 75 MUg fentanyl, in total 20 mL. The
      concentration of lidocaine was determined using the up-and-down method, starting
      at 0.8% (a step size of 0.1%). A successful caudal block was defined by no pain
      perception during biopsy. The EC50 of lidocaine for successful caudal block was
      calculated and side effects were evaluated. Results. A total of 23 patients were
      recruited. The EC50 of lidocaine for successful caudal block was 0.53%.
      Conclusions. Lidocaine of 0.53% combined with 75 MUg fentanyl resulted in
      excellent caudal block in 50% of male patients undergoing transrectal ultrasound
      guided prostate biopsy.

PMID- 27872763
TI  - Effects of Microtubule Stabilization by Epothilone B Depend on the Type and Age
      of Neurons.
AB  - Several studies have demonstrated the therapeutic potential of applying
      microtubule- (MT-) stabilizing agents (MSAs) that cross the blood-brain barrier
      to promote axon regeneration and prevent axonal dystrophy in rodent models of
      spinal cord injury and neurodegenerative diseases. Paradoxically, administration
      of MSAs, which have been widely prescribed to treat malignancies, is well known
      to cause debilitating peripheral neuropathy and axon degeneration. Despite the
      growing interest of applying MSAs to treat the injured or degenerating central
      nervous system (CNS), consequences of MSA exposure to neurons in the central and
      peripheral nervous system (PNS) have not been thoroughly investigated. Here, we
      have examined and compared the effects of a brain-penetrant MSA, epothilone B, on
      cortical and sensory neurons in culture and show that epothilone B exhibits both
      beneficial and detrimental effects, depending on not only the concentration of
      drug but also the type and age of a neuron, as seen in clinical settings.
      Therefore, to exploit MSAs to their full benefit and minimize unwanted side
      effects, it is important to understand the properties of neuronal MTs and
      strategies should be devised to deliver minimal effective concentration directly
      to the site where needed.

PMID- 27872762
TI  - Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia
      in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in
      A2A-D2 Heteroreceptor Complexes.
AB  - Our hypothesis is that allosteric receptor-receptor interactions in homo- and
      heteroreceptor complexes may form the molecular basis of learning and memory.
      This principle is illustrated by showing how cocaine abuse can alter the
      adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor
      interactions and hereby induce neural plasticity in the basal ganglia. Studies
      with A2AR ligands using cocaine self-administration procedures indicate that
      antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal
      GABA antireward pathway play a significant role in reducing cocaine induced
      reward, motivation, and cocaine seeking. Anticocaine actions of A2AR agonists can
      also be produced at A2AR homocomplexes in these antireward neurons, actions in
      which are independent of D2R signaling. At the A2AR-D2R heterocomplex, they are
      dependent on the strength of the antagonistic allosteric A2AR-D2R interaction and
      the number of A2AR-D2R and A2AR-D2R-sigma1R heterocomplexes present in the
      ventral striatopallidal GABA neurons. It involves a differential cocaine-induced
      increase in sigma1Rs in the ventral versus the dorsal striatum. In contrast, the
      allosteric brake on the D2R protomer signaling in the A2AR-D2R heterocomplex of
      the dorsal striatopallidal GABA neurons is lost upon cocaine self-administration.
      This is potentially due to differences in composition and allosteric plasticity
      of these complexes versus those in the ventral striatopallidal neurons.

PMID- 27872765
TI  - Cardiac Arrest after Local Anaesthetic Toxicity in a Paediatric Patient.
AB  - We report a case of a paediatric patient undergoing urological procedure in which
      a possible inadvertent intravascular or intraosseous injection of bupivacaine
      with adrenaline in usual doses caused subsequent cardiac arrest, completely
      reversed after administration of 20% intravenous lipid emulsion. Early diagnosis
      of local anaesthetics toxicity and adequate cardiovascular resuscitation
      manoeuvres contribute to the favourable outcome.

PMID- 27872764
TI  - Genetic Regulation of Maternal Oxytocin Response and Its Influences on Maternal
      Behavior.
AB  - We interrogated the genetic modulation of maternal oxytocin response and its
      association with maternal behavior using genetic risk scores within the oxytocin
      receptor (OXTR) gene. We identified a novel SNP, rs968389, to be significantly
      associated with maternal oxytocin response after a challenging mother-infant
      interaction task (Still Face Paradigm) and maternal separation anxiety from the
      infant. Performing a multiallelic analysis across OXTR by calculating a
      cumulative genetic risk score revealed a significant gene-by-environment (G * E)
      interaction, with OXTR genetic risk score interacting with adult separation
      anxiety to modulate levels of maternal sensitivity. Mothers with higher OXTR
      genetic risk score and adult separation anxiety showed significantly reduced
      levels of maternal sensitivity during free play with the infant. The same G * E
      interaction was also observed for the extended OXTR cumulative genetic risk score
      that included rs968389. Moreover, the extended cumulative OXTR genetic risk score
      itself was found to be significantly associated with maternal separation anxiety
      as it specifically relates to the infant. Our results suggest a complex montage
      of individual and synergistic genetic mediators of maternal behavior. These
      findings add to specific knowledge about genetic regulation of maternal oxytocin
      response in relation to maternal adjustment and infant bonding through the first
      few months of life.

PMID- 27872766
TI  - An Atypical Case of Myxedema Coma with Concomitant Nonconvulsive Seizure.
AB  - Hypothyroidism is a prevalent condition in the general population that is
      treatable with appropriately dosed thyroid hormone replacement medication.
      Infrequently, patients will present with myxedema coma, characterized by
      hypothermia, hypotension, bradycardia, and altered mental status in the setting
      of severe hypothyroidism. Myxedema coma has also been known to manifest in a
      number of unusual and dangerous forms. Here, we present the case of a woman we
      diagnosed with an uncharacteristic expression of myxedema coma and nonconvulsive
      seizure complicated by a right middle cerebral artery infarct.

PMID- 27872767
TI  - Diffuse Alveolar Hemorrhage Associated with Edoxaban Therapy.
AB  - Introduction. The main adverse effect of anticoagulant therapy is bleeding, and
      major bleeding, including intracranial, gastrointestinal, and retroperitoneal
      bleeding, has been reported as an adverse effect of edoxaban, a direct oral
      anticoagulant (DOAC). Bleeding during systemic anticoagulation with edoxaban
      presents a therapeutic conundrum, because there is currently no safe or
      efficacious reversal agent to stop major bleeding. Case Report. A 51-year-old
      woman had multiple traumatic injuries, including lower limb fractures. On day 8,
      she developed deep venous thrombosis, and edoxaban was administered orally. On
      day 38, she developed fungemia, which was treated with an antifungal drug. On day
      43, she presented with dyspnea. Chest computed tomography scan showed bilateral
      diffuse ground-glass opacities in the whole lung fields. The results of the
      subsequent workup (i.e., serum levels of the antineutrophil cytoplasmic antibody,
      antinuclear antibody, and antiglomerular basement membrane antibody) and
      microbiological study were unremarkable. Based on these findings, her condition
      was diagnosed as diffuse alveolar hemorrhage (DAH) associated with edoxaban
      therapy. The lung opacities disappeared spontaneously after edoxaban therapy was
      discontinued. Conclusion. DAH is a dangerous complication associated with
      edoxaban therapy. DOACs, including edoxaban, should be prescribed with caution,
      especially for patients in a critical condition.

PMID- 27872768
TI  - Hip Replacement Surgery in 14-Year-Old Girl with Factor V Deficiency: Haemostatic
      Treatment and Thromboprophylaxis.
AB  - Factor V (FV) is a pivotal coagulation factor present in plasma and platelets. It
      plays an essential role in secondary haemostasis acting as a cofactor in the
      prothrombinase complex, catalysing the conversion of prothrombin to thrombin.
      There is little evidence on the management of mayor orthopaedic surgery in
      paediatric or adolescents subjects with this coagulopathy and almost no
      information about thromboprophylaxis in these situations. We report a case of a
      hip replacement in a 14-year-old girl with moderate FV deficiency (0.07 IU mL-1).
      As haemostatic replacement, inactivated fresh frozen plasma (FFP) was transfused
      at doses of 600 mL (15 mL kg-1, 45 kg weight) 2 hours before surgery and then
      sequential FFP infusions of 250 mL (7 mL kg-1) every 12 hours for 7 days. Plasma
      factor VIII, von Willebrand factor antigen, and von Willebrand ristocetin
      cofactor were monitored to avoid supranormal levels. Since the patient was
      sexually mature (Marshall and Tanner stage 5) with the hormone replacement
      therapy, she was immobilized and the surgery was considered as a high thrombotic
      risk. Thus, low molecular weight heparin was administered at doses of
      intermediate risk (Enoxaparin 20 mg daily, by weight) after finishing the daily
      infusion of plasma: 24 hours and during the 7 days after intervention. No
      tranexamic acid was used. No haemorrhagic or thrombotic adverse event was
      described.

PMID- 27872769
TI  - Mantle Cell Hyperplasia of Peripheral Lymph Nodes as Initial Manifestation of
      Sickle Cell Disease.
AB  - Sickle cell disease (SCD) is a well known hemoglobinopathy with usual
      manifestations including anemia, hyperbilirubinemia, and vasoocclusive
      complications. Despite presence of mild splenomegaly in early phase of the
      disease, lymphadenopathy is not an often finding of SCD. We introduce an
      undiagnosed case of SCD who presented in third decade of his life with multiple
      cervical lymphadenopathies and mild splenomegaly persistent for about five years.
      Histopathologic examination of the resected lymph nodes showed expansion of the
      mantle cell layers of secondary follicles as well as several monomorphic mantle
      cell nodules. To rule out possibility of a malignant process involving lymph
      nodes, an immunohistochemical panel was ordered which was in favor of benign
      mantle cell hyperplasia. Immunoglobulin gene rearrangement study showed no clonal
      bands and confirmed benign nature of the process. Respecting mild abnormalities
      on Complete Blood Count, peripheral blood smear was reviewed revealing some
      typical sickle red blood cells as well as rare nucleated red blood cells.
      Solubility test for hemoglobin (HB) S was positive. Hemoglobin electrophoresis
      confirmed diagnosis of homozygous HbS disease.

PMID- 27872770
TI  - Herpes Simplex Virus Hepatitis in an Immunocompetent Host Resembling Hepatic
      Pyogenic Abscesses.
AB  - Herpes simplex virus (HSV) hepatitis represents a rare complication of HSV
      infection, which can progress to acute liver failure and, in some cases, death.
      We describe an immunocompetent 67-year-old male who presented with one week of
      fever and abdominal pain. Computed tomography (CT) scan and magnetic resonance
      imaging (MRI) of the abdomen showed multiple bilobar hepatic lesions, some with
      rim enhancement, compatible with liver abscesses. Subsequent liver biopsy,
      however, revealed hepatocellular necrosis, HSV-type intranuclear inclusions, and
      immunostaining positive for herpes virus type 2 (HSV-2). Though initially treated
      with broad-spectrum antibiotics, following histologic diagnosis of HSV hepatitis,
      the patient was transitioned to intravenous acyclovir for four weeks and he
      achieved full clinical recovery. Given its high mortality and nonspecific
      presentation, one should consider HSV hepatitis in all patients with acute
      hepatitis with multifocal hepatic lesions of unknown etiology. Of special note,
      this is only the second reported case of HSV liver lesions mimicking pyogenic
      abscesses on CT and MRI.

PMID- 27872771
TI  - Tranexamic Acid: An Exceedingly Rare Cause of Anaphylaxis during Anaesthesia.
AB  - Tranexamic acid (TXA) allergy is extremely rare. An 80-year-old woman without
      prior exposure to TXA underwent elective knee replacement. Shortly after
      induction of anaesthesia and intravenous TXA, she developed hypotension,
      tachycardia, and facial erythema accompanied by a raised serum tryptase. Later,
      skin prick and intradermal testing confirmed positive responses to TXA in high
      dilution and with negative results to the other drugs used. While neuromuscular
      blocking agents, opiates, and antibiotics remain the most frequent cause of
      anaphylaxis during anaesthesia, allergy to TXA should always be borne in mind and
      requires skin testing for confirmation as there are presently no blood tests
      available.

PMID- 27872772
TI  - An Uncommon Feature of Chronic Granulomatous Disease in a Neonate.
AB  - Chronic Granulomatous Disease (CGD) represents recurrent life-threatening
      bacterial and fungal infections and granuloma formation with a high mortality
      rate. CGD's sign and symptoms usually appear in infancy and children before the
      age of five; therefore, its presentation in neonatal period with some uncommon
      features may be easily overlooked. Here we describe a case of CGD in a 24-day-old
      boy, presenting with a diffuse purulent vesiculopustular rash and multiple
      osteomyelitis.

PMID- 27872774
TI  - Pulmonary Kaposi Sarcoma: An Uncommon Cause of Respiratory Failure in the Era of
      Highly Active Antiretroviral Therapy-Case Report and Review of the Literature.
AB  - Kaposi Sarcoma (KS) is the most common malignancy associated with Acquired Immune
      Deficiency Syndrome (AIDS) and is caused by Human Herpesvirus 8 (HHV 8) or Kaposi
      Sarcoma Herpesvirus (KSHV). In about 90% of cases Kaposi Sarcoma is associated
      with cutaneous lesions; however visceral disease can occur in the absence of
      cutaneous involvement. In the era of Highly Active Antiretroviral Therapy
      (HAART), the incidence of KS has declined. Clinical features of pulmonary KS
      might be difficult to distinguish from pneumonia in the immunocompromised
      patients and could lead to diagnostic challenges. First-line treatment of KS is
      with HAART and the incidence has declined with its use. Systemic chemotherapy may
      play a role depending on the extent of the disease. We report the case of a young
      man who presented with pulmonary symptoms and was later found to have pulmonary
      KS. Interestingly this diagnosis was made in the absence of the classic skin
      lesions. His disease was complicated by progressive respiratory failure and he
      eventually died.

PMID- 27872773
TI  - Bacteremia Caused by Kocuria kristinae from Egypt: Are There More? A Case Report
      and Review of the Literature.
AB  - Kocuria kristinae is opportunistic Gram-positive cocci from the family
      Micrococcaceae. It is usually considered part of the normal flora that rarely is
      isolated from clinical specimens. Here, we report a case of Kocuria kristinae
      bacteremia; to the best of our knowledge, this is the first report from Egypt.

PMID- 27872775
TI  - Infrarenal Aorta Thrombosis Associated with H1N1 Influenza A Virus Infection.
AB  - Influenza viruses are members of the Orthomyxoviridae family, of which influenza
      A, B, and C viruses constitute three separate genera. Arterial thrombosis
      associated with H1N1 influenza A virus infection has rarely been reported. A
      Turkish man aged 28 years was admitted to our emergency department with dyspnea,
      bilateral lower extremity insensitivity, and cold. He reported symptoms of fever,
      myalgia, and cough, which he had had for fifteen days before being admitted to
      our hospital. The patient was tested for pandemic influenza A (H1N1) virus using
      polymerase chain reaction (PCR) tests, which were positive. Abdominal
      computerized tomography with contrast revealed a large occlusive thrombus within
      the infrarenal aorta.

PMID- 27872776
TI  - Cerebral Venous Sinus Thrombosis during Everest Expedition: A Case Report and
      Review of the Literature.
AB  - Cerebral venous sinus thrombosis (CVST) is a rare but serious disorder that is
      associated with a poor clinical outcome. We report a 35-year-old man who had a
      severe headache and diplopia while climbing Mount Everest. His MR venography
      showed right transverse and right sigmoid sinus thrombosis. He improved on
      anticoagulant and symptomatic measures. Cerebral venous sinus thrombosis at high
      altitude is discussed.

PMID- 27872777
TI  - Optic Disk Pit with Sudden Central Visual Field Scotoma.
AB  - Purpose. To describe a case of optic disk pit (ODP) with sudden central visual
      field scotoma. Methods. A 49-year-old woman presented, reporting sudden painless
      central visual field loss 3 months prior to presentation. Neuroophthalmologic,
      systematic, and laboratory evaluation and full imaging processes were performed.
      Results. Fundoscopy and color photography demonstrated an optic disk pit
      inferotemporally. Perimetry identified central visual field horizontal scotoma.
      OCT revealed absence of serous retinal detachment, but disclosed inner retina
      thinning corresponding to the area of the visual field loss. Fluorescein
      angiography demonstrated delay in the cilioretinal arteries and also disclosed a
      relative delay in the perfusion of an arterial branch off the inferior retinal
      arcade. Clinical and laboratory evaluations were negative for any related
      pathology. Conclusion. Sudden central visual field scotoma in patients with ODP
      may be associated with delayed vascular filling of CRA and retinal arterioles
      within the optic disc anomaly region.

PMID- 27872778
TI  - A Case of Secondary Epiretinal Membrane Spontaneous Release.
AB  - Purpose. To report a rare case of secondary epiretinal membrane (ERM) spontaneous
      separation with subsequent visual restoration. Case Summary. We are reporting a
      case with the history of branch retinal vein occlusion, peripheral retinal
      neovascularization, and retinal photocoagulation. Our examination revealed
      secondary ERM associated with relatively high visual acuity (0.6), and a watchful
      waiting strategy was chosen. During the follow-up, slight visual deterioration,
      progressive deformation of the retinal profile, and an increase in diffuse
      retinal edema were observed. No surgical or laser treatment was performed. On the
      next visit, the spontaneous ERM separation with residual parapapillary fixation,
      the increase in visual acuity (0.9), and the decrease in retinal thickness were
      revealed. Conclusion. Such cases present additional evidence to a deferral
      surgical strategy for the management of patients with ERM and relatively high
      visual acuity.

PMID- 27872779
TI  - Ultra-Wide-Field Fluorescein Angiography in Microscopic Polyangiitis.
AB  - A 25-year-old Hispanic female presented with 5 months of dry eyes and 2 months of
      bilateral photophobia and decreased vision. On examination, she had bilateral
      anterior uveitis and mild disc edema of the left eye. A complete infectious and
      inflammatory work-up was positive for elevated antinuclear antibodies and p-ANCA,
      leading to a diagnosis of microscopic polyangiitis. One year after initial
      treatment and steroid taper, an ultra-wide-field fluorescein angiography revealed
      peripheral vasculitis, outside of the standard traditional field of view, leading
      to an increase in immunomodulatory therapy and illustrating the utility of wide
      field angiography for managing patients with uveitis.

PMID- 27872780
TI  - Primary Lymphangioma of the Palatine Tonsil in a 9-Year-Old Boy: A Case
      Presentation and Literature Review.
AB  - Primary lymphangiomas or lymphangiomatous polyps of the palatine tonsil are rare
      benign lesions that are described infrequently in the literature. The majority of
      the published cases concern adults. We report a case of a lymphangiomatous lesion
      of the right palatine tonsil of a 9-year-old boy. Our clinical suspicion was
      confirmed by the histological examination after tonsillectomy and the diagnosis
      of primary lymphangioma of the tonsil was made. In this case we discuss the
      clinical and histopathological features of this lesion and present a short review
      of the current literature.

PMID- 27872781
TI  - Two Invasive Thymomas Incidentally Found during Coronary Artery Bypass Graft
      Surgery.
AB  - Thymoma, the most common neoplasm of the anterior mediastinum, is a rare tumor of
      thymic epithelium that can be locally invasive. We reported 2 cases of invasive
      thymoma incidentally found during routine coronary artery bypass graft (CABG)
      surgery at Faghihee Hospital of Shiraz University of Medical Sciences of Iran in
      a period of about 6 months. The 2 patients were male and above 60 years old. They
      had no clinical symptoms and radiological evidence of mediastinal mass before
      detection of the tumor during operation. For both patients mass was completely
      excised and sent to the laboratory. The ultimate pathological diagnosis of both
      masses was invasive thymoma (stage 2). There are few reports in which thymomas
      were found incidentally during cardiac surgery. In spite of rare coincidence, due
      to being asymptomatic and possibly invasive, special attention to thymus gland
      during cardiac surgery or other mediastinal surgery and preoperative imaging
      studies seem to be reasonable approach.

PMID- 27872782
TI  - Angiosarcoma Arising in Ovarian Mucinous Tumor: A Challenge in Intraoperative
      Frozen Section Diagnosis.
AB  - Angiosarcoma of the ovary is rare but represents an aggressive type of malignant
      ovarian neoplasms. The purpose of this report is to describe the features of
      angiosarcoma arising in mucinous tumor that was misinterpreted as a benign
      vascular proliferation during the intraoperative consultation. A 45-year-old
      woman presented with an abdominal mass for 1 month. Exploratory laparotomy was
      performed. A 35 cm right ovarian mass submitted for intraoperative consultation
      was a multicystic mucinous tumor with an 8 cm area of hemorrhagic lesion between
      cystic locules. The frozen section diagnosis was at least mucinous borderline
      tumor. The hemorrhagic area, which was intraoperatively interpreted as organizing
      vessels associated with previous hemorrhage, represented angiosarcoma in
      permanent sections. Angiosarcoma may present a challenge in intraoperative frozen
      section diagnosis of an ovarian mass. The presence of ectatic anastomosing
      vessels with dissecting growth appears to be the clue to a suspicion of
      angiosarcoma. The presence of endothelial atypia provides further support for the
      diagnosis. A macroscopic hemorrhagic area in an ovarian mucinous tumor should be
      evaluated with care, and the possibility of angiosarcoma should be borne in mind.

PMID- 27872783
TI  - Multimodality Cardiac Imaging in a Patient with Kawasaki Disease and Giant
      Aneurysms.
AB  - Kawasaki disease is a well-known cause of acquired cardiac disease in the
      pediatric and adult population, most prevalent in Japan but also seen commonly in
      the United States. In the era of intravenous immunoglobulin (IVIG) treatment, the
      morbidity associated with this disease has decreased, but it remains a serious
      illness. Here we present the case of an adolescent, initially diagnosed with
      Kawasaki disease as an infant, that progressed to giant aneurysm formation and
      calcification of the coronary arteries. We review his case and the literature,
      focusing on the integral role of multimodality imaging in managing Kawasaki
      disease.

PMID- 27872784
TI  - Ciprofloxacin and Clozapine: A Potentially Fatal but Underappreciated
      Interaction.
AB  - Objective. Clozapine provides a 50%-60% response rate in refractory schizophrenia
      but has a narrow therapeutic index and is susceptible to pharmacokinetic
      interactions, particularly with strong inhibitors or inducers of cytochrome P450
      (CYP) 1A2. Case Report. We report the case of a 28-year-old nonsmoking female
      with intellectual disability who was maintained for 3 years on clozapine 100 mg
      orally twice daily. The patient was treated for presumptive urinary tract
      infection with ciprofloxacin 500 mg orally twice daily and two days later
      collapsed and died despite resuscitation efforts. The postmortem femoral
      clozapine plasma level was dramatically elevated at 2900 ng/mL, and the cause of
      death was listed as acute clozapine toxicity. Conclusion. Given the potentially
      fatal pharmacokinetic interaction between clozapine and ciprofloxacin, clinicians
      are advised to monitor baseline clozapine levels prior to adding strong CYP450
      1A2 inhibitors, reduce the clozapine dose by at least two-thirds if adding a 1A2
      inhibitor such as ciprofloxacin, check subsequent steady state clozapine levels,
      and adjust the clozapine dose to maintain levels close to those obtained at
      baseline.

PMID- 27872786
TI  - Congenital Diaphragmatic Hernia with Delayed Presentation.
AB  - Congenital diaphragmatic hernia (CDH) is caused due to abnormal formation of the
      muscular parts of diaphragm. The incidence of CDH in common births ranges from
      1/25000 to 1/30000. Pulmonary hypoplasia and pulmonary hypertension are factors
      that associate with the increase of mortality and morbidity due to CDH. We
      presented a 68-year-old Iranian woman with abdominal pain and tenderness in right
      upper quadrant who was diagnosed as having CDH. The disease was detected using
      chest X-ray and chest and abdomen sonography and confirmed with chest and abdomen
      CT scan with and without oral contrast. A defect was revealed in posterolateral
      right diaphragm with omentum and transverse colon herniated through it. Right
      posterolateral thoracotomy was performed to cure the disease. CT and CXR were the
      two useful methods in diagnosis of CDH in this patient, although CDH detection
      prior to surgery is too challenging because of rare cases and different types of
      CDH. In order to improve clinical cares in adult CDH patients, investigating more
      cases and long term follow-up are recommended.

PMID- 27872785
TI  - Rebleeding of a Splenic Artery Aneurysm after Coil Embolisation.
AB  - Background. Splenic artery aneurysm (SAA) is an uncommon and difficult diagnosis.
      SAA is more common in females. Only 20% of SAA is symptomatic and may present as
      a rupture. A ruptured SAA is associated with a 25% mortality rate. Case
      Presentation. We present a case of a male patient with a bleeding SAA that
      rapidly increased in size. Distal coiling was technically impossible and despite
      proximal coil embolisation the SAA continued to bleed. A laparotomy including
      splenectomy and partial pancreatectomy was performed with an uneventful patient
      recovery. Discussion. Endovascular management is currently considered the optimal
      treatment of SAA. However, careful monitoring and follow-up is needed after
      embolisation as rapid recanalization of the SAA may possibly occur, especially
      when distal coiling of the aneurysm is unsuccessful. Conclusion. Endovascular
      treatment of an SAA is not necessarily effective. Surgeons must be prepared to
      perform open procedures to further reduce mortality rates.

PMID- 27872787
TI  - Synchronous Malignant Peripheral Nerve Sheath Tumor and Adenocarcinoma of the
      Prostate: Case Report and Literature Review.
AB  - Malignant Peripheral Nerve Sheath Tumors (MPNSTs) of the prostate are extremely
      rare. A very unusual case of simultaneous adenocarcinoma and MPNST of the
      prostate is reported. A 60-year-old Caucasian male presented for annual urologic
      examination. Digital rectal examination revealed a painless, toughish, and
      asymmetrically enlarged prostate. Serum prostate-specific antigen was 1 ng/mL.
      Radiologic examinations demonstrated a large mass, which was arising from the
      left peripheral lobe of the prostate. The patient underwent transrectal
      ultrasound-guided biopsy of the prostate which revealed a smooth muscle tumor of
      uncertain malignant potential. Radical retropubic prostatectomy with en bloc
      removal of the mass and the seminal vesicles was performed and histology
      demonstrated low-grade MPNST and adenocarcinoma of the prostate. To the best of
      our knowledge, this is the first report of simultaneous prostatic adenocarcinoma
      and MPNST in the English literature.

PMID- 27872788
TI  - Concomitant Laparoscopic Burch Urethropexy and Combined Vaginal-Laparoscopic Mesh
      Sling Removal (x2) for Pain and Persistent Stress Urinary Incontinence.
AB  - Although midurethral mesh tape slings are considered the standard of care in the
      treatment of female stress urinary incontinence (SUI), complications such as
      pain, dyspareunia, or erosion are known to occur in addition to persistent
      incontinence. The management of these types of mesh sling complications can be
      very complex, especially when the pain is not just isolated to the vagina but
      extends into other areas, such as the abdomen which requires a much more
      extensive dissection. Additionally, if a mesh sling needs to be removed, the
      patient will most likely have a return of her SUI that often necessitates
      subsequent treatment. Vaginal and/or laparoscopic removal or revision of mesh
      tape slings should be considered in patients presenting with complications such
      as vaginal pain, abdominal pain, dyspareunia, or urinary obstructive symptoms. In
      those patients who demonstrate persistent SUI, concomitant laparoscopic Burch
      urethropexy can be considered and can safely be performed at the time mesh
      removal. In this case report we present a patient who required a dual-approach
      removal of two painful midurethral slings in addition to concomitant treatment of
      persistent SUI with a laparoscopic Burch urethropexy procedure.

PMID- 27872789
TI  - Malignant Peripheral Nerve Sheath Tumor of Prostate: A Rare Case Report and
      Literature Review.
AB  - A mid-aged male presented with progressive lower urinary tract symptoms (LUTS)
      for years. Huge prostate with low serum prostate-specific antigen (PSA) level was
      detected. The specimen from transurethral resection revealed surprising pathology
      finding as malignant peripheral nerve sheath tumor (MPNST). Considering its huge
      size (more than 300 gm) and location, we prescribed neoadjuvant chemotherapy
      firstly. The tumor became regressive and then radical surgical resection was
      achieved. Adjuvant multimodality treatment including concurrent chemoradiotherapy
      (CCRT) and target therapy was given. However, he expired about one year later.
      MPNST originating from prostate is very rare and seldom reported before. We here
      present this extremely rare disease and share our treatment experience.

PMID- 27872791
TI  - Antioxidant and Antihyperglycemic Properties of Three Banana Cultivars (Musa
      spp.).
AB  - Background. This study sought to investigate the antioxidant and
      antihyperglycemic properties of Musa sapientum (Latundan banana) (MSL), Musa
      acuminata (Cavendish banana) (MAC), and Musa acuminate (Red Dacca) (MAR).
      Materials and Methods. The sugar, starch, amylose, and amylopectin contents and
      glycemic index (GI) of the three banana cultivars were determined. Furthermore,
      total phenol and vitamin C contents and alpha-amylase and alpha-glucosidase
      inhibitory effects of banana samples were also determined. Results. MAC and MAR
      had the highest starch, amylose, and amylopectin contents and estimated glycemic
      index (eGI) with no significant different while MSL had the lowest. Furthermore,
      MAR (1.07 mg GAE/g) had a higher total phenol content than MAC (0.94 mg GAE/g)
      and MSL (0.96 mg GAE/g), while there was no significant difference in the vitamin
      C content. Furthermore, MAR had the highest alpha-amylase (IC50 = 3.95 mg/mL)
      inhibitory activity while MAC had the least (IC50 = 4.27 mg/mL). Moreover, MAC
      and MAR inhibited glucosidase activity better than MSL (IC50 3.47 mg/mL).
      Conclusion. The low sugar, GI, amylose, and amylopectin contents of the three
      banana cultivars as well as their alpha-amylase and alpha-glucosidase inhibitory
      activities could be possible mechanisms and justification for their
      recommendation in the management of type-2 diabetes.

PMID- 27872790
TI  - Kansas City Cardiomyopathy Questionnaire Utility in Prediction of 30-Day
      Readmission Rate in Patients with Chronic Heart Failure.
AB  - Background. Heart failure (HF) is one of the most common diagnoses associated
      with hospital readmission. We designed this prospective study to evaluate whether
      Kansas City Cardiomyopathy Questionnaire (KCCQ) score is associated with 30-day
      readmission in patients hospitalized with decompensated HF. Methods and Results.
      We enrolled 240 patients who met the study criteria. Forty-eight (20%) patients
      were readmitted for decompensated HF within thirty days of hospital discharge,
      and 192 (80%) patients were not readmitted. Compared to readmitted patients,
      nonreadmitted patients had a higher average KCCQ score (40.8 versus 32.6, P =
      0.019) before discharge. Multivariate analyses showed that a high KCCQ score was
      associated with low HF readmission rate (adjusted OR = 0.566, P = 0.022). The c
      statistic for the base model (age + gender) was 0.617. The combination of home
      medication and lab tests on the base model resulted in an integrated
      discrimination improvement (IDI) increase of 3.9%. On that basis, the KCQQ
      further increased IDI of 2.7%. Conclusions. The KCCQ score determined before
      hospital discharge was significantly associated with 30-day readmission rate in
      patients with HF, which may provide a clinically useful measure and could
      significantly improve readmission prediction reliability when combined with other
      clinical components.

PMID- 27872792
TI  - Porcine Pancreatic Lipase Inhibitory Agent Isolated from Medicinal Herb and
      Inhibition Kinetics of Extracts from Eleusine indica (L.) Gaertner.
AB  - Eleusine indica (Linnaeus) Gaertner is a traditional herb known to be depurative,
      febrifuge, and diuretic and has been reported with the highest inhibitory
      activity against porcine pancreatic lipase (PPL) among thirty two plants screened
      in an earlier study. This study aims to isolate and identify the active
      components that may possess high potential as an antiobesity agent. Of the
      screened solvent fractions of E. indica, hexane fraction showed the highest
      inhibitory activity of 27.01 +/- 5.68% at 100 MUg/mL. Bioactivity-guided
      isolation afforded three compounds from the hexane fraction of E. indica, namely,
      beta-sitosterol, stigmasterol, and lutein. The structures of these compounds were
      elucidated using spectral techniques. Lutein showed an outstanding inhibitory
      activity against PPL (55.98 +/- 1.04%), with activity 60% higher than that of the
      reference drug Orlistat. The other compounds isolated and identified were beta
      sitosterol (2.99 +/- 0.80%) and stigmasterol (2.68 +/- 0.38%). The enzyme
      kinetics of E. indica crude methanolic extract on PPL showed mixed inhibition
      mechanism.

PMID- 27872793
TI  - Improved Methods to Produce Tissue-Engineered Skin Substitutes Suitable for the
      Permanent Closure of Full-Thickness Skin Injuries.
AB  - There is a clinical need for skin substitutes to replace full-thickness skin
      loss. Our group has developed a bilayered skin substitute produced from the
      patient's own fibroblasts and keratinocytes referred to as Self-Assembled Skin
      Substitute (SASS). After cell isolation and expansion, the current time required
      to produce SASS is 45 days. We aimed to optimize the manufacturing process to
      standardize the production of SASS and to reduce production time. The new
      approach consisted in seeding keratinocytes on a fibroblast-derived tissue sheet
      before its detachment from the culture plate. Four days following keratinocyte
      seeding, the resulting tissue was stacked on two fibroblast-derived tissue sheets
      and cultured at the air-liquid interface for 10 days. The resulting total
      production time was 31 days. An alternative method adapted to more contractile
      fibroblasts was also developed. It consisted in adding a peripheral frame before
      seeding fibroblasts in the culture plate. SASSs produced by both new methods
      shared similar histology, contractile behavior in vitro and in vivo evolution
      after grafting onto mice when compared with SASSs produced by the 45-day standard
      method. In conclusion, the new approach for the production of high-quality human
      skin substitutes should allow an earlier autologous grafting for the treatment of
      severely burned patients.

PMID- 27872795
TI  - Heterogeneous autoregressive model with structural break using nearest neighbor
      truncation volatility estimators for DAX.
AB  - High frequency financial data modelling has become one of the important research
      areas in the field of financial econometrics. However, the possible structural
      break in volatile financial time series often trigger inconsistency issue in
      volatility estimation. In this study, we propose a structural break heavy-tailed
      heterogeneous autoregressive (HAR) volatility econometric model with the
      enhancement of jump-robust estimators. The breakpoints in the volatility are
      captured by dummy variables after the detection by Bai-Perron sequential multi
      breakpoints procedure. In order to further deal with possible abrupt jump in the
      volatility, the jump-robust volatility estimators are composed by using the
      nearest neighbor truncation approach, namely the minimum and median realized
      volatility. Under the structural break improvements in both the models and
      volatility estimators, the empirical findings show that the modified HAR model
      provides the best performing in-sample and out-of-sample forecast evaluations as
      compared with the standard HAR models. Accurate volatility forecasts have direct
      influential to the application of risk management and investment portfolio
      analysis.

PMID- 27872796
TI  - Some symmetric identities for the generalized Bernoulli, Euler and Genocchi
      polynomials associated with Hermite polynomials.
AB  - In 2008, Liu and Wang established various symmetric identities for Bernoulli,
      Euler and Genocchi polynomials. In this paper, we extend these identities in a
      unified and generalized form to families of Hermite-Bernoulli, Euler and Genocchi
      polynomials. The procedure followed is that of generating functions. Some
      relevant connections of the general theory developed here with the results
      obtained earlier by Pathan and Khan are also pointed out.

PMID- 27872794
TI  - In silico Identification of Potential Peptides or Allergen Shot Candidates
      Against Aspergillus fumigatus.
AB  - Aspergillus fumigatus is capable of causing invasive aspergillosis or acute
      bronchopulmonary aspergillosis, and the current situation is alarming. There are
      no vaccine or allergen shots available for Aspergillus-induced allergies. Thus, a
      novel approach in designing of an effective vaccine or allergen shot candidate
      against A. fumigatus is needed. Using immunoinformatics approaches from the
      characterized A. fumigatus allergens, we have mapped epitopic regions to predict
      potential peptides that elicit both Aspergillus-specific T cells and B cell
      immune response. Experimentally derived immunodominant allergens were retrieved
      from www.allergen.org. A total of 23 allergenic proteins of A. fumigatus were
      retrieved. Out of 23 allergenic proteins, 13 of them showed high sequence
      similarity to both human and mouse counterparts and thus were eliminated from
      analysis due to possible cross-reactivity. Remaining allergens were subjected to
      T cell (major histocompatibility complex class I and II alleles) and B cell
      epitope prediction using immune epitope database analysis resource. Only five
      allergens have shown a common B and T cell epitopic region between human and
      mouse. They are Asp f1 {147-156 region (RVIYTYPNKV); Mitogillin}, Asp f2 {5-19
      region (LRLAVLLPLAAPLVA); Hypothetical protein}, Asp f5 {305-322 region
      (LNNYRPSSSSLSFKY); Metalloprotease}, Asp f17 {98-106 region (AANAGGTVY);
      Hypothetical protein}, and Asp f34 {74-82 region (YIQDGSLYL); PhiA cell wall
      protein}. The epitopic region from these five allergenic proteins showed
      potential for development of single peptide- or multipeptide-based vaccine or
      allergen shots for experimental prioritization.

PMID- 27872797
TI  - Lovastatin lowers the risk of breast cancer: a population-based study using
      logistic regression with a random effects model.
AB  - BACKGROUND: Laboratory studies have demonstrated statin-induced apoptosis of
      cancer cells, including breast cancer cells, and evidence is accumulating on the
      mechanism of statin-induced apoptosis. However, despite numerous epidemiological
      studies, no consensus has been reached regarding the relationship between statin
      use and breast cancer risk. METHODS: This retrospective case-control study
      enrolled 4332 breast cancer patients and 21,660 age-matched controls registered
      in the National Health Insurance program of Taiwan, which covers approximately
      99% of the population. The study cases were women for whom a diagnosis of breast
      cancer (ICD-9-CM code 174.X) had been recorded in LHID2005 between January 1,
      2004 and December 31, 2010. A logistic regression model was adjusted for
      potential confounding factors, including the level of urbanization, and the
      Charlson Comorbidity Index was applied to assess potential comorbidities. We also
      considered possible bias caused by random urbanization, because nutrition and
      lifestyle factors are related to breast cancer incidence. RESULTS: Our results
      showed that lovastatin was associated with a lower risk of breast cancer
      (adjusted OR 0.596; 95% CI 0.497-0.714; p < 0.001), and atorvastatin exhibited a
      protective tendency against breast cancer (adjusted OR 0.887; 95% CI 0.776-1.013;
      p < 0.077). CONCLUSIONS: Although no consensus has been established regarding the
      relationship between statin use and breast cancer risk, our study indicated that
      lovastatin is a potential chemopreventive agent against breast cancer. Further
      detailed research is warranted.

PMID- 27872798
TI  - Factors affecting executive functions in obstructive sleep apnea syndrome and
      volumetric changes in the prefrontal cortex.
AB  - PURPOSE: Obstructive sleep apnea syndrome (OSAS) is associated with cognitive
      changes and executive functions are among the cognitive domains most affected.
      However, it is not completely understood which of the factor(s) among hypoxemia,
      repeated arousal, and sleepiness affect the executive functions. This study aims
      to evaluate the possible relationship between the executive functions and
      nocturnal parameters, Epworth Sleepiness Scale (ESS) scores, and prefrontal
      cortex (PFC) volumes. PATIENTS AND METHODS: A total of 28 patients aged between
      18 and 60 years who were newly diagnosed with OSAS were included in this study.
      The Wisconsin Card Sorting Test (WCST) and Stroop test which were used in the
      evaluation of executive functions were applied to all patients. Cranial magnetic
      resonance imaging (MRI) and volumetric measurements of the PFC were performed.
      Polysomnography (PSG), WCST, Stroop test, and cranial MRI were also applied to
      the control group which consisted of age- and education status-matched 15 healthy
      subjects. The correlation of WCST and Stroop tests and PFC volume, PSG
      parameters, and ESS scale was examined. RESULTS: The WCST-6 test scores were
      statistically significantly higher in the patient group (p = 0.022; p < 0.05).
      Additionally, the Stroop test 5 (p = 0.043) and Stroop test-5 correction (p =
      0.005) measurements were statistically significantly higher in the patient group
      (p < 0.05). A negative and statistically significant correlation was found
      between the WCST-4 and WCST-10 and ESS measurements in the patient group (r 
      0.452; p 0.016; p < 0.05; r -0.437; p 0.020; p < 0.05). However, there was no
      correlation between the PSG parameters and WCST and Stroop test scores. No
      statistically significant differences in the MRI volumetric measurements of the
      PFC were found between the patient and control groups. CONCLUSIONS: Impairment in
      the attentive and executive functions in OSAS is evident. The most influential
      factor is excessive daytime sleepiness, rather than hypoxemia and severity of the
      disease.

PMID- 27872799
TI  - A systematic literature review of open source software quality assessment models.
AB  - BACKGROUND: Many open source software (OSS) quality assessment models are
      proposed and available in the literature. However, there is little or no adoption
      of these models in practice. In order to guide the formulation of newer models so
      they can be acceptable by practitioners, there is need for clear discrimination
      of the existing models based on their specific properties. Based on this, the aim
      of this study is to perform a systematic literature review to investigate the
      properties of the existing OSS quality assessment models by classifying them with
      respect to their quality characteristics, the methodology they use for
      assessment, and their domain of application so as to guide the formulation and
      development of newer models. Searches in IEEE Xplore, ACM, Science Direct,
      Springer and Google Search is performed so as to retrieve all relevant primary
      studies in this regard. Journal and conference papers between the year 2003 and
      2015 were considered since the first known OSS quality model emerged in 2003.
      RESULTS: A total of 19 OSS quality assessment model papers were selected. To
      select these models we have developed assessment criteria to evaluate the quality
      of the existing studies. Quality assessment models are classified into five
      categories based on the quality characteristics they possess namely: single
      attribute, rounded category, community-only attribute, non-community attribute as
      well as the non-quality in use models. Our study reflects that software selection
      based on hierarchical structures is found to be the most popular selection method
      in the existing OSS quality assessment models. Furthermore, we found that
      majority (47%) of the existing models do not specify any domain of application.
      CONCLUSIONS: In conclusion, our study will be a valuable contribution to the
      community and helps the quality assessment model developers in formulating newer
      models and also to the practitioners (software evaluators) in selecting suitable
      OSS in the midst of alternatives.

PMID- 27872801
TI  - "Beauty contest" indicator of cognitive ability and free riding strategies.
      Results from a scenario experiment about pandemic flu immunization.
AB  - High immunization coverage rates are desirable in order to reduce total morbidity
      and mortality rates, but it may also provide an incentive for herd immunity free
      riding strategies. The aim of this paper was to investigate the link between
      cognitive ability and vaccination intention in a hypothetical scenario experiment
      about Avian Flu immunization. A between-subject scenario experiment was utilized
      to examine the willingness to undergo vaccination when the vaccination coverage
      was proclaimed to be 36, 62 and 88%. Respondents were later assigned to a "Beauty
      contest" experiment, an experimental game commonly used to investigate
      individual's cognitive ability. Results show that there was a significant
      negative effect of the proclaimed vaccination uptake among others on the
      vaccination intention. However, there were no significant association between the
      "Beauty contest" indicator of cognitive ability and the use of herd immunity free
      riding strategies.

PMID- 27872800
TI  - Invisible seams: Preventing childhood obesity through an improved obstetrics
      pediatrics care continuum.
AB  - Progress in altering the current obesity epidemic among children and adolescents
      remains elusive. Evidence continues to underscore the challenges of altering
      weight status as children age. Further, weight loss interventions among children
      and adults alike tend to demonstrate efficacy in the short-term, however
      individuals tend to slowly revert back to their original weight status over time.
      New understanding of obesity's early origins suggests the need to rethink current
      approaches, particularly within healthcare. Instead of a predominant focus on
      "mid-flight course corrections," healthcare should consider the "take-off" time
      period for health trajectories. This means improved support and promotion of
      healthy behaviors before and after birth, and with both the mother and infant. To
      meet the challenge, greater continuity will be required across obstetrics and
      pediatrics, which often operate independently, focused on different clinical
      outcomes. Likewise, there is an urgent need to remedy a significant skills gap
      within both practices. Through its connection with almost every new mother,
      healthcare plays a unique and vital role in maternal and child health outcomes. A
      more seamless obstetrics-pediatrics care continuum could better address the early
      origins of obesity, factors that we are coming to learn have life-long
      consequences.

PMID- 27872802
TI  - Park use is associated with less sedentary time among low-income parents and
      their preschool child: The NET-Works study.
AB  - INTRODUCTION: Parks are an important component of the neighborhood environment,
      and their presence is believed to support higher levels of physical activity
      among residents. The present study examined park use frequency among a sample of
      534 low-income parents of preschool aged children. Associations with child and
      parent physical activity, neighborhood characteristics and physical
      characteristics of the block immediately surrounding the home were examined.
      METHODS: Data are from baseline measurements completed in 2012-2014 as part of
      larger study (NET-Works: Now Everybody Together for Amazing and Healthy Kids)
      targeting low-income preschool children and their parents (N = 534 parent-child
      dyads). Physical activity was measured in parent and child using accelerometry.
      Parents reported their frequency of use with their child of parks within a half
      kilometer from their residence. Block audits were performed by trained research
      staff to describe the quality and walkability of the streets around the home.
      STATISTICAL ANALYSIS: Bivariate associations between demographic variables,
      perceptions of the neighborhood environment, parent support for child physical
      activity, and physical activity were examined using regression or Chi square
      analysis. RESULTS: Park use frequency was not significantly associated with child
      accelerometry light, moderate or vigorous physical activity. However, it was
      marginally significantly inversely associated with child accelerometry sedentary
      time (p < 0.06). Television viewing hours on weekend days (but not on weekdays)
      were significantly fewer among children in the high park use group compared with
      children who visited the park less frequently (p < 0.01). Park use frequency was
      significantly positively associated with parent accelerometry moderate physical
      activity (p < 0.004), and was significantly inversely associated with parent
      accelerometry sedentary time (p < 0.002). Frequent park use was significantly
      positively associated with parent report of the child frequency of being taken to
      a park or playground outside the home (p < 0.0001), past week visit to park and
      recreation center (p < 0.0001) and parent-reported supportive behaviors for child
      physical activity (p < 0.0001). Parents who reported having to cross busy streets
      to reach play areas reported less frequent park use (p < 0. 02). Walkable
      neighborhoods (p < 0.003) and more incivilities (p < 0.02) in the immediate block
      surrounding the home were significantly associated with more frequent park use.
      CONCLUSIONS: Frequent park use with their preschool child may support higher
      levels of physical activity among low-income parents and reduce sedentary time
      for both child and parent.

PMID- 27872804
TI  - Pulmonary hypertension secondary to pulmonary veno-occlusive disease complicated
      by right heart failure, hypotension and acute kidney injury.
AB  - Pulmonary veno-occlusive disease (PVOD) is rare condition which can lead to
      severe pulmonary hypertension, right ventricular dysfunction, and cardiopulmonary
      failure. The diagnosis of PVOD can be challenging due to its nonspecific symptoms
      and its similarity to idiopathic pulmonary arterial hypertension and interstitial
      lung disease in terms of diagnostic findings. This case describes a 57 year old
      female patient who presented with a 5-month history of progressive dyspnea on
      exertion and nonproductive cough. Workup at another hospital was nonspecific and
      the patient underwent surgical lung biopsy due to concern for interstitial lung
      disease. She subsequently became hemodynamically unstable and was transferred to
      our hospital where she presented with severe hypoxemia, hypotension, and
      suprasystemic pulmonary artery pressures. Preliminary lung biopsy results
      suggested idiopathic pulmonary arterial hypertension and the patient was started
      on vasodilating agents, including continuous epoprostenol infusion. Pulmonary
      artery pressures decreased but remained suprasystemic and the patient did not
      improve. Final review of the biopsy by a specialized laboratory revealed a
      diagnosis of PVOD after which vasodilating therapy was immediately weaned off.
      Evaluation for dual heart-lung transplantation was begun. The patient's hospital
      course was complicated by hypotension requiring vasopressors, worsening right
      ventricular dysfunction, and acute kidney injury. During the transplantation
      evaluation, the patient decided that she did not want to undergo continued
      attempts at stabilization of her progressive multi-organ dysfunction and she was
      transitioned to comfort care. She expired hours after removing inotropic support.

PMID- 27872803
TI  - Local food environment and fruit and vegetable consumption: An ecological study.
AB  - Ecological studies are essential for understanding the environment-diet
      relationship. The purpose of this study was to describe environmental conditions
      and their relationship with fruit and vegetable (FV) consumption among Brazilian
      public health service users in the city of Belo Horizonte. We evaluated food
      stores contained within 1600 m buffer zones at 18 Health Academy Programme sites,
      from 2013 to 2014. Variables at the community (density, proximity and type) and
      the consumer (sectional location of FV; availability, quality, variety, price and
      advertising of FV and ultra-processed foods) nutrition environment were measured
      by direct observation, while aggregate data from users (income and FV
      consumption) were obtained by interview. Data were analysed using the Kernel
      intensity estimator, average nearest neighbour value and Local Moran's Index for
      local spatial autocorrelation. We interviewed 3414 users and analysed 336 food
      stores. Major geographical variations in the FV consumption were identified.
      Average consumption was higher (site 2A: 410.5 +/- 185.7 g vs. site 4B: 311.2 +/-
      159.9 g) in neighbourhoods with higher income and concentration of food stores,
      and better index of access to healthy foods. Sites with poor FV consumption had
      the most stores with poor access to healthy foods (index in the first tertile, <=
      10). In conclusion, negative characteristics of the food environment, as seen in
      the present study, may contribute to low FV consumption, suggesting the need for
      the development and consolidation of public policies aimed at creating healthy
      environments through built environment interventions that increase access to and
      consumption of healthy foods like FV.

PMID- 27872805
TI  - Sevoflurane Induced Diffuse Alveolar Hemorrhage in a young patient.
AB  - We report a very rare case of Sevoflurane Induced Diffuse Alveolar Hemorrhage in
      a previously healthy young adult in the post-operative period following general
      anesthesia. Diffuse alveolar hemorrhage (DAH) associated with inhalation injury
      from halogenated gases is a unique entity in the literature that practicing
      clinicians should be cognizant of and considered in post-operative cases of acute
      respiratory distress whereby other etiologies have been excluded.

PMID- 27872806
TI  - Case report: A rare case of eosinophilic cholecystitis presenting after talc
      pleurodesis for recurrent pneumothorax.
AB  - Eosinophilic cholecystitis (EC) is a rare inflammatory condition of the
      gallbladder, confirmed by a cellular infiltrate comprised of more than 90%
      eosinophils in the gallbladder wall on histological examination. Although the
      etiology of EC is largely unknown, local autoimmune reactions within the
      gallbladder wall to inflammatory mediators from distal sites of inflammation have
      been hypothesized. Talc pleurodesis (TP) is a common clinical procedure used
      within respiratory medicine. However, it is associated with activation of
      systemic acute inflammatory responses including an increase in serum interleukin
      8 (IL-8), which is a potent mediator of eosinophil chemotaxis. We report a case
      of EC following a TP procedure for persistent, secondary pneumothorax.

PMID- 27872807
TI  - Identification of the stria medullaris thalami using diffusion tensor imaging.
AB  - BACKGROUND: Deep brain stimulation (DBS) via anatomical targeting of white matter
      tracts defined by diffusion tensor imaging (DTI) may be a useful tool in the
      treatment of pathologic neurophysiologic circuits implicated in certain disease
      states like treatment resistant depression (TRD). We sought to determine if DTI
      could be used to define the stria medullaris thalami (SM), the major afferent
      white matter pathway to the lateral habenula (LHb), a thalamic nucleus implicated
      in the pathophysiology of TRD. METHODS: Probabilistic DTI was performed on ten
      cerebral hemispheres in five patients who underwent preoperative MRI for DBS
      surgery. Manual identification of the LHb on axial T1 weighted MRI was used for
      the initial seed region for tractography. Variations in tractography depending on
      chosen axial slice of the LHb and chosen voxel within the LHb were also assessed.
      RESULTS: In all hemispheres the SM was reliably visualized. Variations in chosen
      axial seed slice as well as variations in single seed placement did not lead to
      significant changes in SM tractography. CONCLUSIONS: Probabilistic DTI can be
      used to visualize the SM which may ultimately provide utility for direct anatomic
      targeting in DBS surgery.

PMID- 27872808
TI  - Delineation of cortical pathology in multiple sclerosis using multi-surface
      magnetization transfer ratio imaging.
AB  - The purpose of our study was to evaluate the utility of measurements of cortical
      surface magnetization transfer ratio (csMTR) on the inner, mid and outer cortical
      boundaries as clinically accessible biomarkers of cortical gray matter pathology
      in multiple sclerosis (MS). Twenty-five MS patients and 12 matched controls were
      recruited from the MS Clinic of the Montreal Neurological Institute. Anatomical
      and magnetization transfer ratio (MTR) images were acquired using 3 Tesla MRI at
      baseline and two-year time-points. MTR maps were smoothed along meshes
      representing the inner, mid and outer neocortical boundaries. To evaluate csMTR
      reductions suggestive of sub-pial demyelination in MS patients, a mixed model
      analysis was carried out at both the individual vertex level and in anatomically
      parcellated brain regions. Our results demonstrate that focal areas of csMTR
      reduction are most prevalent along the outer cortical surface in the superior
      temporal and posterior cingulate cortices, as well as in the cuneus and
      precentral gyrus. Additionally, age regression analysis identified that
      reductions of csMTR in MS patients increase with age but appear to hit a plateau
      in the outer caudal anterior cingulate, as well as in the precentral and
      postcentral cortex. After correction for the naturally occurring gradient in
      cortical MTR, the difference in csMTR between the inner and outer cortex in focal
      areas in the brains of MS patients correlated with clinical disability. Overall,
      our findings support multi-surface analysis of csMTR as a sensitive marker of
      cortical sub-pial abnormality indicative of demyelination in MS patients.

PMID- 27872809
TI  - Abnormal visuomotor processing in schizophrenia.
AB  - Subtle disturbances of visual and motor function are known features of
      schizophrenia and can greatly impact quality of life; however, few studies
      investigate these abnormalities using simple visuomotor stimuli. In healthy
      people, electrophysiological data show that beta band oscillations in
      sensorimotor cortex decrease during movement execution (event-related beta
      desynchronisation (ERBD)), then increase above baseline for a short time after
      the movement (post-movement beta rebound (PMBR)); whilst in visual cortex, gamma
      oscillations are increased throughout stimulus presentation. In this study, we
      used a self-paced visuomotor paradigm and magnetoencephalography (MEG) to
      contrast these responses in patients with schizophrenia and control volunteers.
      We found significant reductions in the peak-to-peak change in amplitude from ERBD
      to PMBR in schizophrenia compared with controls. This effect was strongest in
      patients who made fewer movements, whereas beta was not modulated by movement in
      controls. There was no significant difference in the amplitude of visual gamma
      between patients and controls. These data demonstrate that clear abnormalities in
      basic sensorimotor processing in schizophrenia can be observed using a very
      simple MEG paradigm.

PMID- 27872810
TI  - The association between intra- and juxta-cortical pathology and cognitive
      impairment in multiple sclerosis by quantitative T2* mapping at 7 T MRI.
AB  - Using quantitative T2* at 7 Tesla (T) magnetic resonance imaging, we investigated
      whether impairment in selective cognitive functions in multiple sclerosis (MS)
      can be explained by pathology in specific areas and/or layers of the cortex.
      Thirty-one MS patients underwent neuropsychological evaluation, acquisition of 7
      T multi-echo T2* gradient-echo sequences, and 3 T anatomical images for cortical
      surfaces reconstruction. Seventeen age-matched healthy subjects served as
      controls. Cortical T2* maps were sampled at various depths throughout the cortex
      and juxtacortex. Relation between T2*, neuropsychological scores and a cognitive
      index (CI), calculated from a principal component analysis on the whole battery,
      was tested by a general linear model. Cognitive impairment correlated with T2*
      increase, independently from white matter lesions and cortical thickness, in
      cortical areas highly relevant for cognition belonging to the default-mode
      network (p < 0.05 corrected). Dysfunction in different cognitive functions
      correlated with longer T2* in selective cortical regions, most of which showed
      longer T2* relative to controls. For most tests, this association was strongest
      in deeper cortical layers. Executive dysfunction, however, was mainly related
      with pathology in juxtameningeal cortex. T2* explained up to 20% of the variance
      of the CI, independently of conventional imaging metrics (adjusted-R2: 52-67%, p
      < 5.10- 4). Location of pathology across the cortical width and mantle showed
      selective correlation with impairment in differing cognitive domains. These
      findings may guide studies at lower field strength designed to develop surrogate
      markers of cognitive impairment in MS.

PMID- 27872812
TI  - Anti-Inflammatory Effects of the Essential Oils of Ginger (Zingiber officinale
      Roscoe) in Experimental Rheumatoid Arthritis.
AB  - Ginger and its extracts have been used traditionally as anti-inflammatory
      remedies, with a particular focus on the medicinal properties of its phenolic
      secondary metabolites, the gingerols. Consistent with these uses, potent anti
      arthritic effects of gingerol-containing extracts were previously demonstrated by
      our laboratory using an experimental model of rheumatoid arthritis, streptococcal
      cell wall (SCW)-induced arthritis. In this study, anti-inflammatory effects of
      ginger's other secondary metabolites, the essential oils (GEO), which contain
      terpenes with reported phytoestrogenic activity, were assessed in female Lewis
      rats with SCW-induced arthritis. GEO (28 mg/kg/d ip) prevented chronic joint
      inflammation, but altered neither the initial acute phase of joint swelling nor
      granuloma formation at sites of SCW deposition in liver. Pharmacologic doses of
      17-beta estradiol (200 or 600 MUg/kg/d sc) elicited the same pattern of anti
      inflammatory activity, suggesting that GEO could be acting as a phytoestrogen.
      However, contrary to this hypothesis, GEO had no in vivo effect on classic
      estrogen target organs, such as uterus or bone. En toto, these results suggest
      that ginger's anti-inflammatory properties are not limited to the frequently
      studied phenolics, but may be attributable to the combined effects of both
      secondary metabolites, the pungent-tasting gingerols and as well as its aromatic
      essential oils.

PMID- 27872813
TI  - Complete genome sequence of the biofilm-forming Curtobacterium sp. strain BH-2-1
      1, isolated from lettuce (Lactuca sativa) originating from a conventional field
      in Norway.
AB  - Here, we present the 3,795,952 bp complete genome sequence of the biofilm-forming
      Curtobacterium sp. strain BH-2-1-1, isolated from conventionally grown lettuce
      (Lactuca sativa) from a field in Vestfold, Norway. The nucleotide sequence of
      this genome was deposited into NCBI GenBank under the accession CP017580.

PMID- 27872811
TI  - Failure to mobilize cognitive control for challenging tasks correlates with
      symptom severity in schizophrenia.
AB  - Deficits in the adaptive, flexible control of behavior contribute to the clinical
      manifestations of schizophrenia. We used functional MRI and an antisaccade
      paradigm to examine the neural correlates of cognitive control deficits and their
      relations to symptom severity. Thirty-three chronic medicated outpatients with
      schizophrenia and 31 healthy controls performed an antisaccade paradigm. We
      examined differences in recruitment of the cognitive control network and task
      performance for Hard (high control) versus Easy (low control) antisaccade trials
      within and between groups. We focused on the key regions involved in 'top-down'
      control of ocular motor structures - dorsal anterior cingulate cortex,
      dorsolateral and ventrolateral prefrontal cortex. In patients, we examined
      whether difficulty implementing cognitive control correlated with symptom
      severity. Patients made more errors overall, and had shorter saccadic latencies
      than controls on correct Hard vs. Easy trials. Unlike controls, patients failed
      to increase activation in the cognitive control network for Hard vs. Easy trials.
      Reduced activation for Hard vs. Easy trials predicted higher error rates in both
      groups and increased symptom severity in schizophrenia. These findings suggest
      that patients with schizophrenia are impaired in mobilizing cognitive control
      when presented with challenges and that this contributes to deficits suppressing
      prepotent but contextually inappropriate responses, to behavior that is stimulus
      bound and error-prone rather than flexibly guided by context, and to symptom
      expression. Therapies aimed at increasing cognitive control may improve both
      cognitive flexibility and reduce the impact of symptoms.

PMID- 27872814
TI  - Transcriptional profiles of WNV neurovirulence in a genetically diverse
      Collaborative Cross population.
AB  - West Nile Virus (WNV) is a mosquito-transmitted virus from the Flaviviridae
      family that causes fever in 1 in 5 infected people. WNV can also become neuro
      invasive and cross the blood-brain barrier leading to severe neurological
      symptoms in a subset of WNV infected individuals [1]. WNV neuro-invasion is
      believed to be influenced by a number of factors including host genetics. In
      order to explore these effects and recapitulate the complex immune genetic
      differences among individuals, we studied gene expression following WNV infection
      in the Collaborative Cross (CC) model. The CC is a mouse genetics resource
      composed of > 70 independently bred, octo-parental recombinant inbred mouse lines
      [2]. To identify the individual host gene expression signatures influencing
      protection or susceptibility to WNV disease and WNV neuroinvasion, we used the
      nanostring nsolver platform to quantify gene expression in brain tissue isolated
      from WNV-infected CC mice at days 4, 7 and 12 post-infection [3]. This nanostring
      technology provided a high throughput, non-amplification based mRNA quantitation
      method to detect immune genes involved in neuro-invasion. Data was deposited into
      the Gene Expression Omnibus (GEO) under accession GSE85999.

PMID- 27872815
TI  - The complete mitochondrial genome of the acid-tolerant fungus Penicillium ShG4C.
AB  - Complete mitochondrial genome of the acid-tolerant fungus Penicillium ShG4C,
      isolated from oxidized sediments of an abandoned polymetallic mine site, has been
      sequenced using high-throughput sequencing approach. The mitochondrial genome
      represents a circular DNA molecule with size of 26,725 bp. It encodes a usual set
      of mitochondrial genes, including 15 protein coding genes, large and small
      ribosomal RNAs and 27 tRNA genes. All genes are located on H-strand DNA and
      transcribed in one direction. Taxonomic analysis based on concatenated sequences
      of mitochondrial proteins confirmed taxonomic position of this fungus within the
      genus Penicillium. The sequence of the complete mitochondrial genome of
      Penicillium ShG4C was deposited in DBBJ/EMBL/GenBank under accession number
      KX931017.

PMID- 27872816
TI  - Evidence of triple mutant Pfdhps ISGNGA haplotype in Plasmodium falciparum
      isolates from North-east India: An analysis of sulfadoxine resistant haplotype
      selection.
AB  - BACKGROUND: North-east region of India has consistent role in the spread of multi
      drug resistant Plasmodium (P.) falciparum to other parts of Southeast Asia. After
      rapid clinical treatment failure of Artemisinin based combination therapy
      Sulphadoxine/Pyrimethamine (ACT-SP) chemoprophylaxis, Artemether-Lumefantrine
      (ACT-AL) combination therapy was introduced in the year 2012 in this region for
      the treatment of uncomplicated P. falciparum malaria. In a DNA sequencing based
      polymorphism analysis, seven codons of P. falciparum dihydropteroate synthetase
      (Pfdhps) gene were screened in a total of 127 P. falciparum isolates collected
      from Assam, Arunachal Pradesh and Tripura of North-east India during the year
      2014 and 2015 to document current sulfadoxine resistant haplotypes. MATERIALS AND
      METHODS: Sequences were analyzed to rearrange both nucleotide and protein
      haplotypes. Molecular diversity indices were analyzed in DNA Sequence
      Polymorphism software (DnaSP) on the basis of Pfdhps gene sequences.
      Disappearance from selective neutrality was assessed based on the ratio of non
      synonomous to synonomous nucleotide substitutions [dN/dS ratio]. Moreover, two
      tailed Z test was performed in search of the significance for probability of
      rejecting null hypothesis of strict neutrality [dN = dS]. Presence of mutant P.
      falciparum multidrug resistance protein1 (Pfmdr1) was also checked in those
      isolates that were present with new Pfdhps haplotypes. Phylogenetic relationship
      based on Pfdhps gene was reconstructed in Molecular Evolutionary Genetics
      Analysis (MEGA). RESULTS: Among eight different sulfadoxine resistant haplotypes
      found, IS GNG A haplotype was documented in a total of five isolates from Tripura
      with association of a new mutant M538 R allele. Sequence analysis of Pfmdr1 gene
      in these five isolates came to notice that not all but only one isolate was
      mutant at codon 86 (N86 Y ; Y YSND) in the multidrug resistance protein.
      Molecular diversity based on Pfdhps haplotypes revealed that P. falciparum
      populations in Assam and Tripura were under balancing selection for sulfadoxine
      resistant haplotypes but population from Arunachal Pradesh was under positive
      selection with comparatively high haplotype diversity (h = 0.870). In
      reconstructed phylogenetic analysis, isolates having IS GNG A haplotype were
      grouped into two separate sub-clusters from the other isolates based on their
      genetic distances and diversities. CONCLUSION: This study suggests that
      sulfadoxine resistant isolates are still migrating from its epicenter to the
      other parts of Southeast Asia and hence control and elimination of the drug
      resistant isolates have become impedimental. Moreover, P. falciparum populations
      in different areas may undergo selection of particular sulfadoxine resistant
      haplotypes either in the presence of drug or after its removal to maintain their
      plasticity.

PMID- 27872817
TI  - Draft whole-genome sequence of the Diaporthe helianthi 7/96 strain, causal agent
      of sunflower stem canker.
AB  - Diaporthe helianthi is a fungus pathogenic to sunflower. Virulent strains of this
      fungus cause stem canker with important yield losses and reduction of oil
      content. Here we present the first draft whole-genome sequence of the highly
      virulent isolate D. helianthi strain 7/96, thus providing a useful platform for
      future research on stem canker of sunflower and fungal genomics. The genome
      sequence of the D. helianthi isolate 7/96 was deposited at DDBJ/ENA/GenBank under
      the accession number MAVT00000000 (BioProject PRJNA327798).

PMID- 27872818
TI  - De novo transcriptome assembly of Schisandra chinensis Turcz. (Baill.).
AB  - The fruit of Schisandra chinensis Turcz. (Baill.), namely "Wuweizi" in China, is
      a well-known herbal medicine and health food. At present, research focused on the
      extraction of effective chemical component and function identification. Little
      known about the secondary metabolism gene pathway of chemical composition. Its
      fruit color usually red, however, the white fruit color variation has been found.
      It made us interested in exploring which gene change lead to this result. In
      order to understand the genetic background of S. chinensis, we performed a
      transcriptome analysis of S. chinensis, including red fruit and skin of 'Yanhong'
      cultivar and white fruit and skin of 'Jinwuwei'. We obtained 26.4 GB raw data
      (NCBI accession number: SSR4449123). De novo transcriptome assembly using Trinity
      revealed 92,415 transcripts and generated 71,443 unigenes. All unigenes were
      annotated in database. This study provides transcriptome of S. chinensis, which
      might be useful for comparative transcriptome analyses and understand gene
      expression of secondary metabolites.

PMID- 27872821
TI  - Isolated Non-ascitic Peritoneal Carcinomatosis from Metastatic Prostate Cancer.
AB  - Prostate cancer most commonly metastasizes to bone, lung and liver. Omental
      metastasis of prostate cancer is extremely rare, with only a few cases reported
      in the literature, many of which have associated ascites. We present a case of
      non-ascitic omental metastasis of prostate cancer without any bone metastases.
      Furthermore, this patient has had two negative measurements of circulating tumor
      cells (CTCs) in the blood, suggesting a non-hematogenous route of metastasis to
      the omentum.

PMID- 27872820
TI  - Nine-year experience in Gaucher disease diagnosis at the Spanish reference center
      Fundacion Jimenez Diaz.
AB  - BACKGROUND: Fundacion Jimenez Diaz (FJD) is a reference center for genetic
      diagnosis of Gaucher disease (GD) in Spain. Genetic analyses of acid beta
      glucosidase (GBA) gene using different techniques were performed to search for
      new mutations, in addition to those previously and most frequently found in the
      Spanish population. Additionally, the study of the chitotriosidase (CHIT1) gene
      was used to assess the inflammatory status of patients in the follow-up of enzyme
      replacement therapy (ERT). We present the genetic data gathered during the last
      nine years at FJD. METHODS: Blood samples from patients with suspected GD were
      collected for enzymatic and genetic analyses. The genetic analysis was performed
      on DNA from 124 unrelated suspected cases and 57 relatives from 2007 to 2015,
      starting with a mutational screening kit, followed by Sanger sequencing of the
      entire gene and other techniques to look for deletions. CHIT1 was also studied to
      assess the reliability of this biomarker. RESULTS: In 46 out of 93 GD patients
      (49.5%) the two mutant alleles were found. We detected 21 different mutations.
      The most common mutation was N370S (c.126A > G; p.Asp409Ser current nomenclature)
      (in 50.5% of patients), followed by L444P (c.1448T > C; p.Leu483Pro current
      nomenclature) (in 24.7%). The most common heterozygous compound genotype observed
      (18.3%) was c.1226A > G/c.1448T > C (N370S/L444P). Two novel mutations were found
      (del. Ex.4-11 and c.1296G > T; pW432C), as well as p.S146L, only once previously
      reported. Two patients showed the homozygous state for the duplication of CHIT1.
      CONCLUSION: N370S and L444P are the most common mutations and other mutations
      associated to Parkinson's disease have been observed. This should be taken into
      account in the genetic counseling of GD patients.

PMID- 27872819
TI  - Diagnosis of a mild peroxisomal phenotype with next-generation sequencing.
AB  - Peroxisomal biogenesis disorders (PBD) are caused by mutations in PEX genes, and
      are typically diagnosed with biochemical testing in plasma followed by
      confirmatory testing. Here we report the unusual diagnostic path of a child
      homozygous for PEX1 p.G843D. The patient presented with sensorineural hearing
      loss, pigmentary retinopathy, and normal intellect. After testing for Usher
      syndrome was negative, he was found to have PBD through a research sequencing
      panel. When evaluating a patient with hearing loss and pigmentary retinopathy,
      mild PBD should be on the differential regardless of cognitive function.

PMID- 27872822
TI  - Automating hESC differentiation with 3D printing and legacy liquid handling
      solutions.
AB  - Historically, the routine use of laboratory automation solutions has been
      prohibitively expensive for many laboratories. As legacy hardware has begun to
      emerge on the secondary market, automation is becoming an increasingly affordable
      option to augment workflow in virtually any laboratory. To assess the utility of
      legacy liquid handling in stem cell differentiation, a used liquid handling robot
      was purchased at auction to automate a stem cell differentiation protocol that
      gives rise to CD14 + CD45+ mononuclear cells. To maintain sterility, the
      automated liquid handling robot was housed in a custom constructed HEPA filtered
      enclosure. A custom cell scraper and a disposable filter box were designed and 3D
      printed to permit the robot intricate cell culture actions required by the
      protocol. All files for the 3D printed labware are uploaded and are freely
      available. *A used liquid handling robot was used to automate an hESC to monocyte
      differentiation protocol.*The robot-performed protocol induced monocytes as
      effectively as human technicians.*Custom 3D printed labware was made to permit
      certain cell culture actions and are uploaded for free access.

PMID- 27872823
TI  - Serial physical examinations, a simple and reliable tool for managing neonates at
      risk for early-onset sepsis.
AB  - AIM: To investigate whether serial physical examinations (SPEs) are a safe tool
      for managing neonates at risk for early-onset sepsis (EOS). METHODS: This is a
      retrospective cohort study of neonates (>= 34 wks' gestation) delivered in three
      high-volume level IIIbirthing centres in Emilia-Romagna (Italy) during a 4-mo
      period (from September 1 to December 31, 2015). Neonates at risk for EOS were
      managed according to the SPEs strategy, these were carried out in turn by bedside
      nursing staff and physicians. A standardized form detailing general wellbeing,
      skin colour and vital signs was filled in and signed at standard intervals (at
      age 3, 6, 12, 18, 36 and 48 h) in neonates at risk for EOS. Three independent
      reviewers reviewed all charts of neonates and abstracted data (gestational age,
      mode of delivery, group B streptococcus status, risk factors for EOS, duration of
      intrapartum antibiotic prophylaxis, postpartum evaluations, therapies and
      outcome). Rates of sepsis workups, empirical antibiotics and outcome of neonates
      at-risk (or not) for EOS were evaluated. RESULTS: There were 2092 live births and
      1 culture-proven EOS (Haemophilus i) (incidence rates of 0.48/1000 live births).
      Most newborns with signs of illness (51 out of 101, that is 50.5%), and most of
      those who received postpartum antibiotics (17 out of 29, that is 58.6%) were not
      at risk for EOS. Compared to neonates at risk, neonates not at risk for EOS were
      less likely to have signs of illness (51 out of 1442 vs 40 out of 650, P = 0.009)
      or have a sepsis workup (25 out of 1442 vs 28 out of 650, P < 0.001). However,
      they were not less likely to receive empirical antibiotics (17 out of 1442 vs 12
      out of 650, P = 0.3). Thirty-two neonates were exposed to intrapartum fever or
      chorioamnionitis: 62.5% (n = 20) had a sepsis workup and 21.9% (n = 7) were given
      empirical antibiotics. Among 216 neonates managed through the SPEs strategy, only
      5.6% (n = 12) had subsequently a sepsis workup and only 1.9% (n = 4) were given
      empirical antibiotics. All neonates managed through SPEs had a normal outcome.
      Among 2092 neonates, only 1.6% (n = 34) received antibiotics; 1.4% (n = 29) were
      ill and 0.2% (n = 5) were asymptomatic (they were treated because of risk factors
      for EOS). CONCLUSION: The SPEs strategy reduces unnecessary laboratory
      evaluations and antibiotics, and apparently does not worsen the outcome of
      neonates at-risk or neonates with mild, equivocal, transient symptoms.

PMID- 27872824
TI  - Packed red blood cell transfusions as a risk factor for parenteral nutrition
      associated liver disease in premature infants.
AB  - AIM: To determine if packed red blood cell transfusions contribute to the
      development of parenteral nutrition associated liver disease. METHODS: A
      retrospective chart review of 49 premature infants on parenteral nutrition for >
      30 d who received packed red blood cell (PRBC) transfusions was performed.
      Parenteral nutrition associated liver disease was primarily defined by direct
      bilirubin (db) > 2.0 mg/dL. A high transfusion cohort was defined as receiving >
      75 mL packed red blood cells (the median value). Kaplan-Meier plots estimated the
      median volume of packed red blood cells received in order to develop parenteral
      nutrition associated liver disease. RESULTS: Parenteral nutritional associated
      liver disease (PNALD) was noted in 21 (43%) infants based on db. Among the 27
      high transfusion infants, PNALD was present in 17 (64%) based on elevated direct
      bilirubin which was significantly greater than the low transfusion recipients.
      About 50% of the infants, who were transfused 101-125 mL packed red blood cells,
      developed PNALD based on elevation of direct bilirubin. All infants who were
      transfused more than 200 mL of packed red blood cells developed PNALD. Similar
      results were seen when using elevation of aspartate transaminase or alanine
      transaminase to define PNALD. CONCLUSION: In this retrospective, pilot study
      there was a statistically significant correlation between the volume of PRBC
      transfusions received by premature infants and the development of PNALD.

PMID- 27872825
TI  - Clinical profile and outcomes of pediatric endogenous endophthalmitis: A report
      of 11 cases from South India.
AB  - AIM: To study the clinical profile and outcomes of pediatric endogenous
      endophthalmitis from a tertiary eye hospital in South India. METHODS: A total of
      13 eyes of 11 children presented to us with varied symptoms and presentations of
      endogenous endophthalmitis, over a five-year period from January 2010 to December
      2015 were studied. Except for two eyes of a patient, vitreous aspirates were
      cultured from all 11 eyes to isolate the causative organism. These eleven eyes
      also received intravitreal injections. All patients were treated with systemic
      antibiotics. RESULTS: Two cases had bilateral endophthalmitis. Ages ranged from 4
      d to 11 years. Five cases were undiagnosed and treated, before being referred to
      our center. Ten of the 13 eyes underwent a core vitrectomy. The vitrectomy was
      done at an average on the second day after presenting (range 0-20 d). Five of the
      11 vitreous aspirates showed isolates. The incriminating organisms were bacteria
      in three and fungus in two. An underlying predisposing factor was found in seven
      patients. At a mean follow-up 21.5 mo, outcome was good in 7 eyes of 6 cases
      (54%), five eyes of four cases (38%) ended up with phthisis bulbi while one child
      died of systemic complications. CONCLUSION: Endogenous endophthalmitis is a
      challenge for ophthalmologists. Early diagnosis and intervention is the key for a
      better outcome.

PMID- 27872826
TI  - Pandemic influenza 2009: Impact of vaccination coverage on critical illness in
      children, a Canada and France observational study.
AB  - AIM: To study the impact of vaccination critical illness due to H1N1pdm09, we
      compared the incidence and severity of H1N1pdm09 infection in Canada and France.
      METHODS: We studied two national cohorts that included children with documented
      H1N1pdm09 infection, admitted to a pediatric intensive care unit (PICU) in Canada
      and in France between October 1, 2009 and January 31, 2010. RESULTS: Vaccination
      coverage prior to admission to PICUs was higher in Canada than in France (21% vs
      2% of children respectively, P < 0.001), and in both countries, vaccination
      coverage prior to admission of these critically ill patients was substantially
      lower than in the general pediatric population (P < 0.001). In Canada, 160
      children (incidence = 2.6/100000 children) were hospitalized in PICU compared to
      125 children (incidence = 1.1/100000) in France (P < 0.001). Mortality rates were
      similar in Canada and France (4.4% vs 6.5%, P = 0.45, respectively), median
      invasive mechanical ventilation duration and mean PICU length of stay were
      shorter in Canada (4 d vs 6 d, P = 0.02 and 5.7 d vs 8.2 d, P = 0.03,
      respectively). H1N1pdm09 vaccination prior to PICU admission was associated with
      a decreased risk of requiring invasive mechanical ventilation (OR = 0.30, 95%CI:
      0.11-0.83, P = 0.02). CONCLUSION: The critical illness due to H1N1pdm09 had a
      higher incidence in Canada than in France. Critically ill children were less
      likely to have received vaccination prior to hospitalization in comparison to
      general population and children vaccinated had lower risk of ventilation.

PMID- 27872827
TI  - Zinc supplementation as an adjunct to standard therapy in childhood nephrotic
      syndrome - a systematic review.
AB  - AIM: To evaluate the role of zinc as add on treatment to the "recommended
      treatment" of nephrotic syndrome (NS) in children. METHODS: All the published
      literature through the major databases including Medline/Pubmed, Embase, and
      Google Scholar were searched till 31st December 2015. Reference lists from the
      articles were reviewed to identify additional pertinent articles. Retrieved
      papers concerning the role of zinc in childhood NS were reviewed by the authors,
      and the data were extracted using a standardized data collection tool. Randomized
      trials (RCTs) comparing zinc vs placebo was included. Effect of zinc was studied
      in both steroid sensitive and steroid dependent/frequent relapsing NS. The
      primary outcome measure was the risk of relapse in 12 mo. The secondary outcome
      measures were mean relapse rate per patient in 12 mo, mean relapse rate per
      patient in 6 mo, risk of infection associated relapse in 12 mo, cumulative dose
      of steroids in two groups, mean length of time to next relapse, adverse effects
      of therapy, and change in serum zinc levels. RESULTS: Of 54 citations retrieved,
      a total of 6 RCTs were included. Zinc was used at a dose of 10-20 mg/d, for the
      duration that varied from 6-12 mo. Compared to placebo, zinc reduced the
      frequency of relapses, induced sustained remission/no relapse, reduced the
      proportion of infection episodes associated with relapse with a mild adverse
      event in the form of metallic taste. The GRADE evidence generated was of "very
      low-quality". CONCLUSION: Zinc may be a useful additive in the treatment of
      childhood NS. The evidence generated mostly was of "very low-quality". We need
      more good quality RCTs in different country setting as well different subgroups
      of children before any firm recommendation can be made.

PMID- 27872828
TI  - Middle East respiratory syndrome coronavirus disease is rare in children: An
      update from Saudi Arabia.
AB  - AIM: To summarize the reported Middle East respiratory syndrome-coronavirus (MERS
      CoV) cases, the associated clinical presentations and the outcomes. METHODS: We
      searched the Saudi Ministry of Health website, the World Health Organization
      website, and the Flutracker website. We also searched MEDLINE and PubMed for the
      keywords: Middle East respiratory syndrome-coronavirus, MERS-CoV in combination
      with pediatric, children, childhood, infancy and pregnancy from the initial
      discovery of the virus in 2012 to 2016. The retrieved articles were also read to
      further find other articles. Relevant data were placed into an excel sheet and
      analyzed accordingly. Descriptive analytic statistics were used in the final
      analysis as deemed necessary. RESULTS: From June 2012 to April 19, 2016, there
      were a total of 31 pediatric MERS-CoV cases. Of these cases 13 (42%) were
      asymptomatic and the male to female ratio was 1.7:1. The mean age of patients was
      9.8 +/- 5.4 years. Twenty-five (80.6%) of the cases were reported from the
      Kingdom of Saudi Arabia. The most common source of infection was household
      contact (10 of 15 with reported source) and 5 patients acquired infection within
      a health care facility. Using real time reverse transcriptase polymerase chain
      reaction of pediatric patients revealed that 9 out of 552 (1.6%) was positive in
      the Kingdom of Saudi Arabia. CONCLUSION: Utilizing serology for MERS-CoV
      infection in Jordan and Saudi Arabia did not reveal any positive patients. Thus,
      the number of the pediatric MERS-CoV is low; the exact reason for the low
      prevalence of the disease in children is not known.

PMID- 27872829
TI  - Can language acquisition be facilitated in cochlear implanted children?
      Comparison of cognitive and behavioral psychologists' viewpoints.
AB  - AIM: To study how language acquisition can be facilitated for cochlear implanted
      children based on cognitive and behavioral psychology viewpoints? METHODS: To
      accomplish this objective, literature related to behaviorist and cognitive
      psychology prospects about language acquisition were studied and some relevant
      books as well as Medline, Cochrane Library, Google scholar, ISI web of knowledge
      and Scopus databases were searched. Among 25 articles that were selected, only 11
      met the inclusion criteria and were included in the study. Based on the inclusion
      criteria, review articles, expert opinion studies, non-experimental and
      experimental studies that clearly focused on behavioral and cognitive factors
      affecting language acquisition in children were selected. Finally, the selected
      articles were appraised according to guidelines of appraisal of medical studies.
      RESULTS: Due to the importance of the cochlear implanted child's language
      performance, the comparison of behaviorist and cognitive psychology points of
      view in child language acquisition was done. Since each theoretical basis, has
      its own positive effects on language, and since the two are not in opposition to
      one another, it can be said that a set of behavioral and cognitive factors might
      facilitate the process of language acquisition in children. Behavioral
      psychologists believe that repetition, as well as immediate reinforcement of
      child's language behavior help him easily acquire the language during a language
      intervention program, while cognitive psychologists emphasize on the relationship
      between information processing, memory improvement through repetitively using
      words along with "associated" pictures and objects, motor development and
      language acquisition. CONCLUSION: It is recommended to use a combined approach
      based on both theoretical frameworks while planning a language intervention
      program.

PMID- 27872830
TI  - Bacteremia in hemodialysis patients.
AB  - Infection is a common complication and is the second leading cause of death in
      hemodialysis patients. The risk of bacteremia in hemodialysis patients is 26-fold
      higher than in the general population, and 1/2-3/4 of the causative organisms of
      bacteremia in hemodialysis patients are Gram-positive bacteria. The ratio of
      resistant bacteria in hemodialysis patients compared to the general population is
      unclear. Several reports have indicated that hemodialysis patients have a higher
      risk of methicillin-resistant Staphylococcus aureus infection. The most common
      site of infection causing bacteremia is internal prostheses; the use of a
      hemodialysis catheter is the most important risk factor for bacteremia. Although
      antibiotic lock of hemodialysis catheters and topical antibiotic ointment can
      reduce catheter-related blood stream infection (CRBSI), their use should be
      limited to necessary cases because of the emergence of resistant organisms.
      Systemic antibiotic administration and catheter removal is recommended for
      treating CRBSI, although a study indicated the advantages of antibiotic lock and
      guidewire exchange of catheters over systemic antibiotic therapy. An infection
      control bundle recommended by the Center for Disease Control and Prevention
      succeeded in reducing bacteremia in hemodialysis patients with either a catheter
      or arteriovenous fistula. Appropriate infection control can reduce bacteremia in
      hemodialysis patients.

PMID- 27872831
TI  - Outcomes of renal transplant recipients with BK virus infection and BK virus
      surveillance in the Auckland region from 2006 to 2012.
AB  - AIM: To evaluate incidence, risk factors and treatment outcome of BK polyomavirus
      nephropathy (BKVN) in a cohort of renal transplant recipients in the Auckland
      region without a formal BK polyomavirus (BKV) surveillance programme. METHODS: A
      cohort of 226 patients who received their renal transplants from 2006 to 2012 was
      retrospectively reviewed. RESULTS: Seventy-six recipients (33.6%) had a BK viral
      load (BKVL) test and 9 patients (3.9%) developed BKVN. Cold ischaemia time (HR =
      1.18, 95%CI: 1.04-1.35) was found to be a risk factor for BKVN. Four recipients
      with BKVN had complete resolution of their BKV infection; 1 recipient had BKVL
      less than 625 copies/mL; 3 recipients had BKVL more than 1000 copies/mL and 1 had
      graft failure from BKVN. BKVN has a negative impact on graft function [median
      estimated glomerular filtration rate (eGFR) 22.5 (IQR 18.5-53.0) mL/min per 1.73
      m2, P = 0.015), but no statistically significant difference (P = 0.374) in renal
      allograft function was found among negative BK viraemia group [median eGFR 60.0
      (IQR 48.5-74.2) mL/min per 1.73 m2), positive BK viraemia without BKVN group
      [median eGFR 55.0 (IQR 47.0-76.0) mL/min per 1.73 m2] and unknown BKV status
      group [median eGFR 54.0 (IQR 43.8-71.0) mL/min per 1.73 m2]. The incidence and
      treatment outcomes of BKVN were similar to some centres with BKV surveillance
      programmes. CONCLUSION: Recipients with BVKN have poorer graft function. Although
      active surveillance for BKV has been shown to be effective in reducing incidence
      of BKVN, it should be tailored specifically to that transplant centre based on
      its epidemiology and outcomes of BKVN, particularly in centres with limited
      resources.

PMID- 27872832
TI  - Prevalence of risk factors for cardiovascular and kidney disease in Brazilian
      healthy preschool children.
AB  - AIM: To investigate the prevalence of nutritional parameters of risk for
      cardiovascular disease (CVD) and kidney diseases in healthy preschool children.
      METHODS: This is an observational cross-sectional study with 60 healthy children,
      of both genders, aged two to six years old and 56 mothers, in Belo Horizonte,
      Minas Gerais, Brazil. Preschool children and their families with regular
      activities at public schools were invited to paticipate in the study. The
      following characteristics were assessed: Socio-demographic condictions, clinical
      health, anthropometric, biochemical, lifestyle and data on food consumption. The
      56 healthy children were divided into two groups, overweight (C1) and non
      overweight (C2), as well as their mothers, respectively, in overweight (M1) and
      non-overweight (M2). Nutritional status was defined according to results obtained
      through the Anthro(r) Software for nutritional analysis. RESULTS: Thirty-five
      children were male, with mean age of 4.44 +/- 1.0 years old. Eighty-nine percent
      of them were eutrophic, 86.7% were sedentary and they had five meals a day. Body
      mass index (BMI) for age and total cholesterol (TC) was higher on C1 (P = 0.0001)
      and high density lipoprotein cholesterol (HDL-c) was higher on C2. Mothers were
      32.5 +/- 7.1 years old, mostly married and employed. Eighty-six percent of them
      were sedentary and 62.5% were overweight with BMI = 26.38 +/- 5.07 kg/m2.
      Eighteen percent of the overweight mothers had isolated total
      hypercholesterolemia (TC levels elevated) and 12.5% had low HDL-c levels. The
      present study showed an association between overweight and obesity during the
      preschool years and the correspondent mothers' nutritional status of overweight
      and obesity (OR = 4.96; 95%CI: 0.558-44.17). There was a positive correlation
      between the food risk associated with CVD by children and mothers when their
      consumption was 4 times/wk (P = 0.049; r = 0.516) or daily (P = 0.000008; r =
      0.892). CONCLUSION: Analyzed children showed high rates of physical inactivity,
      high serum cholesterol levels and high consumption of food associated with risk
      for CVD and renal disease. Changes in habits should be encouraged early in
      kindergarten.

PMID- 27872833
TI  - Impact of renal transplantation on cardiac morphological and functional
      characteristics in children and adults.
AB  - AIM: To compare the effects of renal transplantation on cardiac functions in
      children and adults. METHODS: One hundred and ten patients attending the
      nephrology outpatient clinic were enrolled in this study and were divided into
      six groups. The first two groups consisted each of 30 renal transplant patients
      who had a successful renal transplantation more than six months, but less than
      one year. Group I were less than 18 years and group II were more than 18 years.
      The third and fourth groups, each were 20 chronic renal failure patients on
      regular hemodialysis. Again, group III were less than 18 years and group IV were
      more than 18 years. Group V and VI (The control Groups) consisted each of 5
      subjects below and above 18 years of age, respectively with normal kidney
      functions. All patients were subjected to history and examination. The kidney
      functions and the hemoglobin were analyzed. After obtaining informed consent,
      echocardiography was done to all patients. RESULTS: There was a statistically
      significant improvement (P < 0.0001) in all cardiac parameters. A regression in
      left ventricular end diastolic volume (LVED) both in children (4.7 +/- 0.8 to 4.2
      +/- 0.5) and in adults (5.9 +/- 0.7 to 4.9 +/- 0.6) were found. There was a
      regression in left ventricular end systolic volume (LVES) both in children (3.1
      +/- 0.6 to 2.4 +/- 0.4) and in adults (4.1 +/- 0.9 to 3.1 +/- 0.5). Fractional
      shortening improves both in children (32.6 +/- 5.3 to 41.7 +/- 7.6) and in adults
      (29.0 +/- 6.6 to 36.5 +/- 4.1). The improvement in ejection fraction (EF) was
      higher in children (59.7 +/- 7.0 to 71.9 +/- 6.1) than in adults (52.0 +/- 12.5
      to 64.8 +/- 5.9). However, this degree of improvement (in children: 12.2 +/- 5.1)
      did not show statistical difference (P-value 0.8), when compared to adults (12.7
      +/- 9.8). CONCLUSION: After renal transplantation cardiac functions and
      morphology (EF/LVED/LVES) do improve markedly and rapidly in both children and
      adults.

PMID- 27872834
TI  - Factors associating with oxygenation of lower-limb muscle tissue in hemodialysis
      patients.
AB  - AIM: To evaluate the lower-limb muscle oxygenation in hemodialysis (HD) patients
      and identify the factors associating with muscle oxygenation. METHODS: Sixty
      seven HD patients (53 men and 14 women; mean age, 67.1 +/- 1.2 years; mean HD
      duration, 5.6 +/- 0.9 years) were recruited. In addition, 15 healthy individuals
      (nine men and six women; mean age, 38.2 +/- 4.6 years) were recruited as the
      control group. Lower-limb muscle regional saturation of oxygen (rSO2) was
      monitored on the lateral side of the gastrocnemius muscle before HD using an
      INVOS 5100C (Covidien Japan, Tokyo, Japan), which utilizes near-infrared
      spectroscopy. Here, we evaluated the association between lower-limb muscle rSO2
      and clinical parameters. RESULTS: The rSO2 values were significantly lower in
      patients undergoing HD than in healthy individuals (50.0% +/- 1.7% vs 76.8% +/-
      2.5%, P < 0.001). Lower-limb muscle rSO2 showed significant positive correlations
      with diastolic blood pressure, blood urea nitrogen concentration, serum
      creatinine concentration, serum potassium concentration, serum inorganic
      phosphate concentration, and serum albumin concentration as well as negative
      correlation with HD duration. We conducted a multiple linear regression analysis
      using parameters that were significantly correlated with the lower-limb muscle
      rSO2 in a simple linear regression analysis. Multiple regression analysis
      demonstrated that lower-limb muscle rSO2 was independently associated with serum
      inorganic phosphate (standardized coefficient: 0.27) and serum albumin
      concentrations (standardized coefficient: 0.24). In addition, there were no
      differences in lower-limb muscle rSO2 between diabetic and non-diabetic HD
      patients. This study has several limitations. Firstly, its sample size was
      relatively small. Secondly, we could not evaluate the association between lower
      limb muscle rSO2 and calculated nutritional markers, including normalized protein
      catabolic rate and body mass index, anthropometric measurements representing
      nutritional status, and the severity of protein-energy wasting. Finally, we did
      not routinely examine the arterial vascular status of HD patients without
      symptoms of peripheral artery disease. As such, it is possible that some HD
      patients with subclinical peripheral artery disease may have been included in
      this study. CONCLUSION: In HD patients, the oxygenation of lower-limb muscle
      tissue was associated with serum inorganic phosphate and albumin concentrations,
      both of which represent nutritional status.

PMID- 27872835
TI  - Six end-stage renal disease patients benefited from first non-simultaneous single
      center 6-way kidney exchange transplantation in India.
AB  - AIM: To avoid desensitization protocols and ABO incompatible kidney
      transplantation (KT) due to high costs and increased risk of infections from
      intense immunosuppression. METHODS: We present institutional ethical review board
      - approved study of single center 6-way kidney exchange transplantation. The
      participants comprised ABO incompatibility (n = 1); positive cross-match and/or
      presence of donor specific antibody (n = 5). The average time required from
      registration in kidney paired donation (KPD) registry to find suitable donors was
      45 d and time required to perform transplants after legal permission was 2 mo.
      RESULTS: Graft and patient survival were 100%, and 100%, respectively. One
      patient had biopsy-proven acute borderline T cell rejection (Banff update 2013,
      type 3). Mean serum creatinine was 0.8 mg/dL at 9 mo follow-up. The waiting time
      in KPD was short as compared to deceased donor KT. CONCLUSION: We report first
      non-simultaneous, single center, 6-way kidney exchange transplantation from
      India. Our experience will encourage other centers in India to undertake this
      practice.

PMID- 27872837
TI  - Antineutrophil cytoplasmic antibodies crescentic allograft glomerulonephritis
      after sofosbuvir therapy.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) are well known to be associated with
      several types of vasculitis, including pauci-immune crescentic
      glomerulonephritis, a form of rapid progressive glomerular nephritis (RPGN). ANCA
      vasculitis has also been reported after administration of propylthiouracil,
      hydralazine, cocaine (adulterated with levimasole), allopurinol, penicillamine
      and few other drugs. All previously reported cases of drug-associated ANCA
      glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug
      for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and
      RPGN following sofosbuvir administration in a kidney transplant recipient. It
      also represents the first case of drug-associated ANCA vasculitis in a
      transplanted kidney. Further drug monitoring is necessary to elucidate the degree
      of association and possible causal effect of sofosbuvir and perinuclear ANCA
      vasculitis.

PMID- 27872836
TI  - Urolithiasis in inflammatory bowel disease and bariatric surgery.
AB  - AIM: To analyse current literature focusing on pathogenesis and therapeutic
      aspects of urolithiasis with inflammatory bowel disease (IBD) and following
      bariatric surgery. METHODS: A systematic literature search was performed using
      PubMed, supplemented with additional references. Studies assessing the
      association of IBD or bariatric surgery with renal stones in both paediatric and
      adulthood were included. RESULTS: Certain types of stones are seen more
      frequently with IBD. Hyperoxaluria and hypocitraturia are the main metabolic
      changes responsible for urolithiasis. The incidence of renal stones in
      malabsorptive types of bariatric surgery such as gastric bypass is high; this is
      not as common in modern restrictive surgical methods. Preventative methods and
      urine alkalinisation have been shown to be beneficial. CONCLUSION: Both
      conditions are associated with renal stones. Patients' counselling and prevention
      strategies are the mainstay of urolithiasis management in these patients.

PMID- 27872838
TI  - New SLC12A3 disease causative mutation of Gitelman's syndrome.
AB  - Gitelman's syndrome (GS) is a salt-losing tubulopathy with an autosomal recessive
      inheritance caused by mutations of SLC12A3, which encodes for the thiazide
      sensitive NaCl cotransporter. In this study we report a new mutation of SLC12A3
      found in two brothers affected by GS. Hypokalemia, hypocalciuria and hyper
      reninemia were present in both patients while hypomagnesemia was detected only in
      one. Both patients are compound heterozygotes carrying one well known GS
      associated mutation (c.2581 C > T) and a new one (c.283delC) in SLC12A3 gene. The
      new mutation results in a possible frame-shift with a premature stop-codon
      (pGln95ArgfsX19). The parents of the patients, heterozygous carriers of the
      mutations found in SLC12A3, have no disease associated phenotype. Therefore, the
      new mutation is causative of GS.

PMID- 27872839
TI  - Insight into the Exoproteome of the Tissue-Derived Trypomastigote form of
      Trypanosoma cruzi.
AB  - The protozoan parasite Trypanosoma cruzi causes Chagas disease, one of the major
      neglected infectious diseases. It has the potential to infect any nucleated
      mammalian cell. The secreted/excreted protein repertoire released by T. cruzi
      trypomastigotes is crucial in host-pathogen interactions. In this study,
      mammalian tissue culture-derived trypomastigotes (Y strain) were used to
      characterize the exoproteome of the infective bloodstream life form. Proteins
      released into the serum-free culture medium after 3 h of incubation were
      harvested and digested with trypsin. NanoLC-MS/MS analysis resulted in the
      identification of 540 proteins, the largest set of released proteins identified
      to date in Trypanosoma spp. Bioinformatic analysis predicted most identified
      proteins as secreted, predominantly by non-classical pathways, and involved in
      host-cell infection. Some proteins possess predicted GPI-anchor signals, these
      being mostly trans-sialidases, mucin associated surface proteins and surface
      glycoproteins. Moreover, we enriched phosphopeptides and glycopeptides from
      tryptic digests. The majority of identified glycoproteins are trans-sialidases
      and surface glycoproteins involved in host-parasite interaction. Conversely, most
      identified phosphoproteins have no Gene Ontology classification. The existence of
      various proteins related to similar functions in the exoproteome likely reflects
      this parasite's enhanced mechanisms for adhesion, invasion, and internalization
      of different host-cell types, and escape from immune defenses.

PMID- 27872841
TI  - Novel Graphical Analyses of Runs of Homozygosity among Species and Livestock
      Breeds.
AB  - Runs of homozygosity (ROH), uninterrupted stretches of homozygous genotypes
      resulting from parents transmitting identical haplotypes to their offspring, have
      emerged as informative genome-wide estimates of autozygosity (inbreeding). We
      used genomic profiles based on 698 K single nucleotide polymorphisms (SNPs) from
      nine breeds of domestic cattle (Bos taurus) and the European bison (Bison
      bonasus) to investigate how ROH distributions can be compared within and among
      species. We focused on two length classes: 0.5-15 Mb to investigate ancient
      events and >15 Mb to address recent events (approximately three generations). For
      each length class, we chose a few chromosomes with a high number of ROH,
      calculated the percentage of times a SNP appeared in a ROH, and plotted the
      results. We selected areas with distinct patterns including regions where (1) all
      groups revealed an increase or decrease of ROH, (2) bison differed from cattle,
      (3) one cattle breed or groups of breeds differed (e.g., dairy versus meat
      cattle). Examination of these regions in the cattle genome showed genes
      potentially important for natural and human-induced selection, concerning, for
      example, meat and milk quality, metabolism, growth, and immune function. The
      comparative methodology presented here permits visual identification of regions
      of interest for selection, breeding programs, and conservation.

PMID- 27872840
TI  - Analysis of Uncertainty and Variability in Finite Element Computational Models
      for Biomedical Engineering: Characterization and Propagation.
AB  - Computational modeling has become a powerful tool in biomedical engineering
      thanks to its potential to simulate coupled systems. However, real parameters are
      usually not accurately known, and variability is inherent in living organisms. To
      cope with this, probabilistic tools, statistical analysis and stochastic
      approaches have been used. This article aims to review the analysis of
      uncertainty and variability in the context of finite element modeling in
      biomedical engineering. Characterization techniques and propagation methods are
      presented, as well as examples of their applications in biomedical finite element
      simulations. Uncertainty propagation methods, both non-intrusive and intrusive,
      are described. Finally, pros and cons of the different approaches and their use
      in the scientific community are presented. This leads us to identify future
      directions for research and methodological development of uncertainty modeling in
      biomedical engineering.

PMID- 27872842
TI  - Transcriptome-Based Analysis of Dof Family Transcription Factors and Their
      Responses to Abiotic Stress in Tea Plant (Camellia sinensis).
AB  - Tea plant (Camellia sinensis (L.) O. Kuntze) is affected by abiotic stress during
      its growth and development. DNA-binding with one finger (Dof) transcription
      factors (TFs) play important roles in abiotic stress tolerance of plants. In this
      study, a total of 29 putative Dof TFs were identified based on transcriptome of
      tea plant, and the conserved domains and common motifs of these CsDof TFs were
      predicted and analyzed. The 29 CsDof proteins were divided into 7 groups (A, B1,
      B2, C1, C2.1, C2.2, and D2), and the interaction networks of Dof proteins in C.
      sinensis were established according to the data in Arabidopsis. Gene expression
      was analyzed in "Yingshuang" and "Huangjinya" under four experimental stresses by
      qRT-PCR. CsDof genes were expressed differentially and related to different
      abiotic stress conditions. In total, our results might suggest that there is a
      potential relationship between CsDof factors and tea plant stress resistance.

PMID- 27872843
TI  - An Engineering Perspective of External Cardiac Loop Recorder: A Systematic
      Review.
AB  - External cardiac loop recorder (ELR) is a kind of ECG monitoring system that
      records cardiac activities of a subject continuously for a long time. When the
      heart palpitations are not the frequent and nonspecific character, it is
      difficult to diagnose the disease. In such a case, ELR is used for long-term
      monitoring of heart signal of the patient. But the cost of ELR is very high.
      Therefore, it is not prominently available in developing countries like India.
      Since the design of ELR includes the ECG electrodes, instrumentation amplifier,
      analog to digital converter, and signal processing unit, a comparative review of
      each part of the ELR is presented in this paper in order to design a cost
      effective, low power, and compact kind of ELR. This review will also give
      different choices available for selecting and designing each part of the ELR
      system. Finally, the review will suggest the better choice for designing a cost
      effective external cardiac loop recorder that helps to make it available even for
      rural people in India.

PMID- 27872844
TI  - Fabrication of Poly(epsilon-caprolactone) Scaffolds Reinforced with Cellulose
      Nanofibers, with and without the Addition of Hydroxyapatite Nanoparticles.
AB  - Biomaterial properties and controlled architecture of scaffolds are essential
      features to provide an adequate biological and mechanical support for tissue
      regeneration, mimicking the ingrowth tissues. In this study, a bioextrusion
      system was used to produce 3D biodegradable scaffolds with controlled
      architecture, comprising three types of constructs: (i) poly(epsilon
      caprolactone) (PCL) matrix as reference; (ii) PCL-based matrix reinforced with
      cellulose nanofibers (CNF); and (iii) PCL-based matrix reinforced with CNF and
      hydroxyapatite nanoparticles (HANP). The effect of the addition and/or
      combination of CNF and HANP into the polymeric matrix of PCL was investigated,
      with the effects of the biomaterial composition on the constructs (morphological,
      thermal, and mechanical performances) being analysed. Scaffolds were produced
      using a single lay-down pattern of 0/90 degrees , with the same processing
      parameters among all constructs being assured. The performed morphological
      analyses showed a satisfactory distribution of CNF within the polymer matrix and
      high reliability was obtained among the produced scaffolds. Significant effects
      on surface wettability and thermal properties were observed, among scaffolds.
      Regarding the mechanical properties, higher scaffold stiffness in the reinforced
      scaffolds was obtained. Results from the cytotoxicity assay suggest that all the
      composite scaffolds presented good biocompatibility. The results of this first
      study on cellulose and hydroxyapatite reinforced constructs with controlled
      architecture clearly demonstrate the potential of these 3D composite constructs
      for cell cultivation with enhanced mechanical properties.

PMID- 27872846
TI  - Effect of Static Load on the Nucleus Pulposus of Rabbit Intervertebral Disc
      Motion Segment in an Organ Culture.
AB  - The development of mechanically active culture systems helps in understanding of
      the role of mechanical stress in intervertebral disc (IVD) degeneration. Motion
      segment cultures facilitate the application and control of mechanical loads. The
      purpose of this study was to establish a culturing method for rabbit IVD motion
      segments to observe the effect of static load on the whole disc organ. Segments
      were cultured in custom-made apparatuses under a constant, compressive load (3
      kg) for 2 weeks. Tissue integrity, matrix synthesis, and matrix gene expression
      profile were assessed and compared with fresh one. The results showed ex vivo
      culturing of samples gradually destroyed the morphology. Proteoglycan contents
      and gene expression were decreased and downregulated obviously. However,
      immunohistochemical staining intensity and collagen type II gene expression were
      significantly enhanced and upregulated. In contrast, these trends were reversed
      under constant compression. These results indicated short-term static load
      stimulated the synthesis of type II collagen; however, constant compression led
      to progressive degeneration and specifically to proteoglycan. Through this study
      a loading and organ-culturing system for ex vivo rabbit IVD motion segments was
      developed, which can be used to study the effects of mechanical stimulation on
      the biology of IVDs and the pathomechanics of IVD degeneration.

PMID- 27872847
TI  - Strengths, Pitfalls, and Lessons from Longitudinal Childhood Asthma Cohorts of
      Children Followed Up into Adult Life.
AB  - Asthma is a common problem worldwide and longitudinal studies of children
      followed up into adult life enable the assessment of clinical outcomes, examine
      the pattern of lung function outcomes, and importantly provide insight into
      aetiology and prognosis for patients with asthma. The aim of this review is to
      examine the major childhood asthma cohort studies which have continued into adult
      life, describing the strengths and weaknesses and the lessons that can be learnt
      regarding pathophysiology and potential future directions for research.

PMID- 27872850
TI  - Frontiers in the Expansion of Bioproducts.

PMID- 27872849
TI  - Automated Segmentation of Coronary Arteries Based on Statistical Region Growing
      and Heuristic Decision Method.
AB  - The segmentation of coronary arteries is a vital process that helps
      cardiovascular radiologists detect and quantify stenosis. In this paper, we
      propose a fully automated coronary artery segmentation from cardiac data volume.
      The method is built on a statistics region growing together with a heuristic
      decision. First, the heart region is extracted using a multi-atlas-based
      approach. Second, the vessel structures are enhanced via a 3D multiscale line
      filter. Next, seed points are detected automatically through a threshold
      preprocessing and a subsequent morphological operation. Based on the set of
      detected seed points, a statistics-based region growing is applied. Finally,
      results are obtained by setting conservative parameters. A heuristic decision
      method is then used to obtain the desired result automatically because parameters
      in region growing vary in different patients, and the segmentation requires full
      automation. The experiments are carried out on a dataset that includes eight
      patient multivendor cardiac computed tomography angiography (CTA) volume data.
      The DICE similarity index, mean distance, and Hausdorff distance metrics are
      employed to compare the proposed algorithm with two state-of-the-art methods.
      Experimental results indicate that the proposed algorithm is capable of
      performing complete, robust, and accurate extraction of coronary arteries.

PMID- 27872848
TI  - Role of Membrane Lipids in the Regulation of Erythrocytic Oxygen-Transport
      Function in Cardiovascular Diseases.
AB  - The composition and condition of membrane lipids, the morphology of erythrocytes,
      and hemoglobin distribution were explored with the help of laser interference
      microscopy (LIM) and Raman spectroscopy. It is shown that patients with
      cardiovascular diseases (CVD) have significant changes in the composition of
      their phospholipids and the fatty acids of membrane lipids. Furthermore, the
      microviscosity of the membranes and morphology of the erythrocytes are altered
      causing disordered oxygen transport by hemoglobin. Basic therapy carried out with
      the use of antiaggregants, statins, antianginals, beta-blockers, and calcium
      antagonists does not help to recover the morphofunctional properties of
      erythrocytes. Based on the results the authors assume that, for the relief of the
      ischemic crisis and further therapeutic treatment, it is necessary to include, in
      addition to cardiovascular disease medicines, medication that increases the
      ability of erythrocytes' hemoglobin to transport oxygen to the tissues. We assume
      that the use of LIM and Raman spectroscopy is advisable for early diagnosis of
      changes in the structure and functional state of erythrocytes when cardiovascular
      diseases develop.

PMID- 27872845
TI  - Recent Nanotechnology Approaches for Prevention and Treatment of Biofilm
      Associated Infections on Medical Devices.
AB  - Bacterial colonization in the form of biofilms on surfaces causes persistent
      infections and is an issue of considerable concern to healthcare providers. There
      is an urgent need for novel antimicrobial or antibiofilm surfaces and biomedical
      devices that provide protection against biofilm formation and planktonic
      pathogens, including antibiotic resistant strains. In this context, recent
      developments in the material science and engineering fields and steady progress
      in the nanotechnology field have created opportunities to design new biomaterials
      and surfaces with anti-infective, antifouling, bactericidal, and antibiofilm
      properties. Here we review a number of the recently developed nanotechnology
      based biomaterials and explain underlying strategies used to make antibiofilm
      surfaces.

PMID- 27872852
TI  - Modelling Seasonal Brucellosis Epidemics in Bayingolin Mongol Autonomous
      Prefecture of Xinjiang, China, 2010-2014.
AB  - Brucellosis is one of the severe public health problems; the cumulative number of
      new human brucellosis cases reached 211515 from 2010 to 2014 in China. Bayingolin
      Mongol Autonomous Prefecture is situated in the southeast of Xinjiang, where
      brucellosis infection occurs every year. Based on the reported data of newly
      acute human brucellosis cases for each season in Bayingolin Mongol Autonomous
      Prefecture, we proposed a susceptible, exposed, infected, and vaccinated (SEIV)
      model with periodic transmission rates to investigate the seasonal brucellosis
      transmission dynamics among sheep/cattle and from sheep/cattle to humans.
      Compared with the criteria of MAPE and RMSPE, the model simulations agree to the
      data on newly acute human brucellosis. We predict that the number of newly acute
      human brucellosis is increasing and will peak 15325 [95% CI: 11920-18242] around
      the summer of 2023. We also estimate the basic reproduction number R0 = 2.5524
      [95% CI: 2.5129-2.6225] and perform some sensitivity analysis of the newly acute
      human brucellosis cases and the basic reproduction number R0 in terms of model
      parameters. Our study demonstrates that reducing the birth number of
      sheep/cattle, raising the slaughter rate of infected sheep/cattle, increasing the
      vaccination rate of susceptible sheep/cattle, and decreasing the loss rate of
      vaccination are effective strategies to control brucellosis epidemic.

PMID- 27872851
TI  - Developmental Toxicity of Carbon Quantum Dots to the Embryos/Larvae of Rare
      Minnow (Gobiocypris rarus).
AB  - The toxic effects of CDs on rare minnow (Gobiocypris rarus) embryos at different
      developmental stages were investigated. The results showed that rare minnow
      embryos had decreased spontaneous movements, body length, increased heart rate,
      pericardial edema, yolk sac edema, tail/spinal curvature, various morphological
      malformations, and decreased hatching rate. Biochemical analysis showed the CDs
      exposure significantly inhibited the activity of Na+/K+-ATPase and Ca2+-ATPase
      and increased the MDA contents and the activity of SOD, CAT, and GPX. Further
      examination suggested that the CDs exposure induced serious embryonic cellular
      DNA damage. Moreover, the CDs exposure induced upregulation of development
      related genes (Wnt8a and Mstn) along with the downregulation of Vezf1. Overall,
      the present study revealed that the CDs exposure has significant development
      toxicity on rare minnow embryos/larvae. Mechanistically, this toxicity might
      result from the pressure of induced oxidative stress coordinate with the
      dysregulated development related gene expression mediated by the CDs exposure.

PMID- 27872853
TI  - Controlled Release of Interleukin-1 Receptor Antagonist from Hyaluronic Acid
      Chitosan Microspheres Attenuates Interleukin-1beta-Induced Inflammation and
      Apoptosis in Chondrocytes.
AB  - This paper investigates the protective effect of interleukin-1 receptor
      antagonist (IL-1Ra) released from hyaluronic acid chitosan (HA-CS) microspheres
      in a controlled manner on IL-1beta-induced inflammation and apoptosis in
      chondrocytes. The IL-1Ra release kinetics was characterized by an initial burst
      release, which was reduced to a linear release over eight days. Chondrocytes were
      stimulated with 10 ng/ml IL-1beta and subsequently incubated with HA-CS-IL-1Ra
      microspheres. The cell viability was decreased by IL-1beta, which was attenuated
      by HA-CS-IL-1Ra microspheres as indicated by an MTT assay. ELISA showed that HA
      CS-IL-1Ra microspheres inhibited IL-1beta-induced inflammation by attenuating
      increases in NO2- and prostaglandin E2 levels as well as increase in
      glycosaminoglycan release. A terminal deoxyribonucleotide transferase
      deoxyuridine triphosphate nick-end labeling assay revealed that the IL-1beta
      induced chondrocyte apoptosis was decreased by HA-CS-IL-1Ra microspheres.
      Moreover, HA-CS-IL-1Ra microspheres blocked IL-1beta-induced chondrocyte
      apoptosis by increasing B-cell lymphoma 2 (Bcl-2) and decreasing Bcl-2-associated
      X protein and caspase-3 expressions at mRNA and protein levels, as indicated by
      reverse-transcription quantitative polymerase chain reaction and western blot
      analysis, respectively. The results of the present study indicated that HA-CS-IL
      1Ra microspheres as a controlled release system of IL-1Ra possess potential anti
      inflammatory and antiapoptotic properties in rat chondrocytes due to their
      ability to regulate inflammatory factors and apoptosis associated genes.

PMID- 27872854
TI  - Identification of Novel Inhibitors against Coactivator Associated Arginine
      Methyltransferase 1 Based on Virtual Screening and Biological Assays.
AB  - Overexpression of coactivator associated arginine methyltransferase 1 (CARM1), a
      protein arginine N-methyltransferase (PRMT) family enzyme, is associated with
      various diseases including cancers. Consequently, the development of small
      molecule inhibitors targeting PRMTs has significant value for both research and
      therapeutic purposes. In this study, together with structure-based virtual
      screening with biochemical assays, two compounds DC_C11 and DC_C66 were
      identified as novel inhibitors of CARM1. Cellular studies revealed that the two
      inhibitors are cell membrane permeable and effectively blocked proliferation of
      cancer cells including HELA, K562, and MCF7. We further predicted the binding
      mode of these inhibitors through molecular docking analysis, which indicated that
      the inhibitors competitively occupied the binding site of the substrate and
      destroyed the protein-protein interactions between CARM1 and its substrates.
      Overall, this study has shed light on the development of small-molecule CARM1
      inhibitors with novel scaffolds.

PMID- 27872855
TI  - Partial Portal Vein Arterialization Attenuates Acute Bile Duct Injury Induced by
      Hepatic Dearterialization in a Rat Model.
AB  - Hepatic infarcts or abscesses occur after hepatic artery interruption. We
      explored the mechanisms of hepatic deprivation-induced acute liver injury and
      determine whether partial portal vein arterialization attenuated this injury in
      rats. Male Sprague-Dawley rats underwent either complete hepatic arterial
      deprivation or partial portal vein arterialization, or both. Hepatic ischemia was
      evaluated using biochemical analysis, light microscopy, and transmission electron
      microscopy. Hepatic ATP levels, the expression of hypoxia- and inflammation
      associated genes and proteins, and the expression of bile transporter genes were
      assessed. Complete dearterialization of the liver induced acute liver injury, as
      evidenced by the histological changes, significantly increased serum biochemical
      markers, decreased ATP content, increased expression of hypoxia- and inflammation
      associated genes and proteins, and decreased expression of bile transporter
      genes. These detrimental changes were extenuated but not fully reversed by
      partial portal vein arterialization, which also attenuated ductular reaction and
      fibrosis in completely dearterialized rat livers. Collectively, complete hepatic
      deprivation causes severe liver injury, including bile infarcts and biloma
      formation. Partial portal vein arterialization seems to protect against acute
      ischemia-hypoxia-induced liver injury.

PMID- 27872856
TI  - Altered Expression of EPO Might Underlie Hepatic Hemangiomas in LRRK2 Knockout
      Mice.
AB  - Parkinson's disease (PD) is a severe neurodegenerative disorder caused by
      progressive loss of dopaminergic neurons in the substantia nigra pars compacta of
      the midbrain. The molecular mechanism of PD pathogenesis is unclear. Mutations in
      the leucine-rich repeat kinase 2 (LRRK2) gene are a common genetic cause of
      familial and sporadic PD. However, studies on LRRK2 mutant mice revealed no
      visible dopaminergic neuronal loss in the midbrain. While surveying a LRRK2
      knockout mouse strain, we found that old animals developed age-dependent hepatic
      vascular growths similar to cavernous hemangiomas. In livers of these hemangioma
      positive LRRK2 knockout mice, we detected an increased expression of the HIF
      2alpha protein and significant reactivation of the expression of the HIF-2alpha
      target gene erythropoietin (EPO), a finding consistent with a role of the HIF
      2alpha pathway in blood vessel vascularization. We also found that the kidney EPO
      expression was reduced to 20% of the wild-type level in 18-month-old LRRK2
      knockout mice. Unexpectedly, this reduction was restored to wild-type levels when
      the knockout mice were 22 months to 23 months old, implying a feedback mechanism
      regulating kidney EPO expression. Our findings reveal a novel function of LRRK2
      in regulating EPO expression and imply a potentially novel relationship between
      PD genes and hematopoiesis.

PMID- 27872857
TI  - Visual and Quantitative Analysis Methods of Respiratory Patterns for Respiratory
      Gated PET/CT.
AB  - We integrated visual and quantitative methods for analyzing the stability of
      respiration using four methods: phase space diagrams, Fourier spectra, Poincare
      maps, and Lyapunov exponents. Respiratory patterns of 139 patients were grouped
      based on the combination of the regularity of amplitude, period, and baseline
      positions. Visual grading was done by inspecting the shape of diagram and
      classified into two states: regular and irregular. Quantitation was done by
      measuring standard deviation of x and v coordinates of Poincare map (SD x , SD v
      ) or the height of the fundamental peak (A1) in Fourier spectrum or calculating
      the difference between maximal upward and downward drift. Each group showed
      characteristic pattern on visual analysis. There was difference of quantitative
      parameters (SD x , SD v , A1, and MUD-MDD) among four groups (one way ANOVA, p =
      0.0001 for MUD-MDD, SD x , and SD v , p = 0.0002 for A1). In ROC analysis, the
      cutoff values were 0.11 for SD x (AUC: 0.982, p < 0.0001), 0.062 for SD v (AUC:
      0.847, p < 0.0001), 0.117 for A1 (AUC: 0.876, p < 0.0001), and 0.349 for MUD-MDD
      (AUC: 0.948, p < 0.0001). This is the first study to analyze multiple aspects of
      respiration using various mathematical constructs and provides quantitative
      indices of respiratory stability and determining quantitative cutoff value for
      differentiating regular and irregular respiration.

PMID- 27872858
TI  - 17beta-Estradiol Promotes Schwann Cell Proliferation and Differentiation,
      Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model.
AB  - Estrogen induces oligodendrocyte remyelination in response to demyelination in
      the central nervous system. Our objective was to determine the effects of 17beta
      estradiol (E2) on Schwann cell function and peripheral nerve remyelination after
      injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve
      transection injury model and were randomly categorized into control and E2
      groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture
      was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were
      isolated from the sciatic nerves of 1- to 3-day-old Sprague-Dawley rats.
      Immunostaining for myelin basic protein (MBP) expression and toluidine blue
      staining for myelin sheaths demonstrated that E2 treatment accelerates early
      remyelination in the "nerve bridge" region between the proximal and distal stumps
      of the transection injury site in the mouse sciatic nerve. The 5-bromo-2'
      deoxyuridine incorporation assay revealed that E2 promotes Schwann cell
      proliferation in the bridge region and in the primary culture, which is blocked
      using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture
      determined showed that the MBP expression in the E2-treated group is higher than
      that in the control group. These results show that E2 promotes Schwann cell
      proliferation and myelination depending on AKT activation.

PMID- 27872859
TI  - Mapping QTLs for Fertility Restoration of Different Cytoplasmic Male Sterility
      Types in Rice Using Two Oryza sativa *O. rufipogon Backcross Inbred Line
      Populations.
AB  - Hybrid rice breeding using cytoplasmic male sterility/fertility restoration
      (CMS/Rf) systems plays an important role in ensuring global food security. Two
      backcross inbred line (BIL) populations derived from either Xieqingzao B
      (XB)//XB/Dongxiang wild rice (DWR) (XXD) or XB//DWR/XB (XDX) were used to detect
      quantitative trait loci (QTLs) for fertility restoration of Dwarf wild abortive-
      (DA-), Indonesia Paddy- (ID-), and DWR-type CMS in rice. Lines with ID- and DA
      type CMS were testcrossed with both the XXD- and XDX-BILs, while the line with
      DWR-type CMS was testcrossed with the XDX-BILs only. A total of 16 QTLs for
      fertility restoration of CMS systems were identified, including three for DWR
      type CMS, six for DA-type CMS, and seven for ID-type CMS. All of the additive
      alleles in the QTLs were derived from Oryza rufipogon. Eleven QTLs were clustered
      in five chromosomal regions, indicating that common Rf loci restored different
      CMS systems, and the favorable O. rufipogon alleles could be used to develop
      restorer lines for various CMS types by marker-assisted selection.

PMID- 27872860
TI  - Danggui Buxue Tang Attenuates Tubulointerstitial Fibrosis via Suppressing NLRP3
      Inflammasome in a Rat Model of Unilateral Ureteral Obstruction.
AB  - Inflammation significantly contributes to the progression of chronic kidney
      disease (CKD). This study aimed to characterize Danggui Buxue Tang (DBT)
      renoprotection and relationship with NOD-like receptors family pyrin domain
      containing 3 (NLRP3) inflammasome expression in rats with unilateral ureteral
      obstruction (UUO). Sprague-Dawley rats were subjected to UUO and randomly
      assigned to untreated UUO, enalapril-treated (10 mg/kg/day), and DBT-treated (9
      g/kg/day) groups. Sham-operated rats served as controls, with 8 rats in each
      group. All rats were sacrificed for blood and renal specimen collection at 14
      days after UUO. Untreated UUO rats exhibited azotemia, intense tubulointerstitial
      collagen deposition, upregulations of tubulointerstitial injury index,
      augmentation levels of collagen I (Col I), alpha-smooth muscle actin (alpha-SMA),
      NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment
      domain (ASC), pro-caspase-1, caspase-1, IL-1beta, and pro-IL-1beta. DBT treatment
      significantly attenuated interstitial collagen deposition and tubulointerstitial
      injury, lowering Col I and alpha-SMA levels. Synchronous expressions of NLRP3,
      ASC, pro-caspase-1, caspase-1, pro-IL-1beta, and IL-1beta decreased in renal
      tissue. In comparison to enalapril, DBT significantly reduced tubulointerstitial
      injury, interstitial collagen deposition, and expressions of Col I and IL-1beta.
      Thus, DBT offers renoprotection in UUO rats, which was associated with
      suppressing NLRP3 inflammasome expression and following reduction of the
      secretion of cytokine IL-1beta. The mechanisms of multitargets of traditional
      Chinese medicine can be better used for antifibrotic treatment.

PMID- 27872861
TI  - Danish Nationwide Data Reveal a Link between Diabetes Mellitus, Diabetic
      Retinopathy, and Glaucoma.
AB  - Aims. To determine the association between treatment against diabetes mellitus
      (DM) and treatment with antiglaucomatous drugs in the entire Danish population
      and to investigate the comorbidity between DM and its complications with
      antiglaucomatous treatment. Methods. Retrospective nationwide cohort study with
      data over a 16-year follow-up period. The National Danish Registry of Medicinal
      Products Statistics was used to identify all claimed prescriptions for
      antiglaucomatous medication and DM drugs. ICD-10 classifications were furthermore
      used to identify comorbidities between antiglaucomatous medication and the DM
      complications, diabetic retinopathy (DR), and nephropathy. Results. A total of
      6,343,747 individuals in the period between 1996 and 2012 were analyzed. The
      overall incidence rate of new-onset glaucoma patients was 0.07 per 1000 person
      years for the reference population compared to 36 per 1000 person-years for all
      diagnosed DM cases. Patients treated with DM drugs had about two times higher
      relative risk of glaucoma, when adjusting for a range of factors. The presence of
      DR alone or in combination with nephropathy increased the risk of glaucoma.
      Conclusions. The present study reports a strong association between DM and onset
      of glaucoma treatment in the entire Danish population.

PMID- 27872863
TI  - Attention Deficit Disorder and Allergic Rhinitis: Are They Related?
AB  - The association between ADHD and allergy remains controversial. Our previous
      findings suggest that nerve growth factor may link the nervous and immune
      systems. The primary objective of this study was to determine if a combination of
      cetirizine + methylphenidate is effective in children with comorbid ADHD and
      allergic rhinitis. We also examined the role of nerve growth factor in these
      comorbidities. Our randomized, double-blind, placebo-controlled, crossover study
      enrolled 38 children diagnosed with comorbid ADHD and allergy using cetirizine (n
      = 12), sustained-release methylphenidate (n = 12), or cetirizine +
      methylphenidate (n = 14). Endpoints compared baseline to posttreatment
      evaluations for allergic rhinitis and ADHD scores. Serum nerve growth factor
      levels were measured using ELISA. For allergy endpoints, combination therapy
      produced results superior to individual therapy. For ADHD, similar scores were
      achieved for individual therapy; however, combination therapy resulted in
      improved scores. Nerve growth factor levels were downregulated following this
      trend. We conclude that ADHD and allergic rhinitis may have common mechanism and
      represent a comorbid condition that links the nervous system to the immune
      system. Further studies are needed.

PMID- 27872862
TI  - Oxygenation of the Intraportally Transplanted Pancreatic Islet.
AB  - Intraportal islet transplantation (IT) is not widely utilized as a treatment for
      type 1 diabetes. Oxygenation of the intraportally transplanted islet has not been
      studied extensively. We present a diffusion-reaction model that predicts the
      presence of an anoxic core and a larger partly functional core within
      intraportally transplanted islets. Four variables were studied: islet diameter,
      islet fractional viability, external oxygen partial pressure (P) (in surrounding
      portal blood), and presence or absence of a thrombus on the islet surface.
      Results indicate that an islet with average size and fractional viability
      exhibits an anoxic volume fraction (AVF) of 14% and a function loss of 72% at a
      low external P. Thrombus formation increased AVF to 30% and function loss to 92%,
      suggesting that the effect of thrombosis may be substantial. External P and islet
      diameter accounted for the greatest overall impact on AVF and loss of function.
      At our institutions, large human alloislets (>200 MUm diameter) account for ~20%
      of total islet number but ~70% of total islet volume; since most of the total
      transplanted islet volume is accounted for by large islets, most of the
      intraportal islet cells are likely to be anoxic and not fully functional.

PMID- 27872864
TI  - F4/80+ Host Macrophages Are a Barrier to Murine Embryonic Stem Cell-Derived
      Hematopoietic Progenitor Engraftment In Vivo.
AB  - Understanding how embryonic stem cells and their derivatives interact with the
      adult host immune system is critical to developing their therapeutic potential.
      Murine embryonic stem cell-derived hematopoietic progenitors (ESHPs) were
      generated via coculture with the bone marrow stromal cell line, OP9, and then
      transplanted into NOD.SCID.Common Gamma Chain (NSG) knockout mice, which lack B,
      T, and natural killer cells. Compared to control mice transplanted with adult
      lineage-negative bone marrow (Lin- BM) progenitors, ESHP-transplanted mice
      attained a low but significant level of donor hematopoietic chimerism. Based on
      our previous studies, we hypothesized that macrophages might contribute to the
      low engraftment of ESHPs in vivo. Enlarged spleens were observed in ESHP
      transplanted mice and found to contain higher numbers of host F4/80+ macrophages
      compared to BM-transplanted controls. In vivo depletion of host macrophages using
      clodronate-loaded liposomes improved the ESHP-derived hematopoietic chimerism in
      the spleen but not in the BM. F4/80+ macrophages demonstrated a striking
      propensity to phagocytose ESHP targets in vitro. Taken together, these results
      suggest that macrophages are a barrier to both syngeneic and allogeneic ESHP
      engraftment in vivo.

PMID- 27872865
TI  - CXCR3, CCR5, and CRTH2 Chemokine Receptor Expression in Lymphocytes Infiltrating
      Thyroid Nodules with Coincident Hashimoto's Thyroiditis Obtained by Fine Needle
      Aspiration Biopsy.
AB  - Objective. To determine the expression of chemokine receptors in lymphocytes from
      thyroid nodules and peripheral blood in patients with and without Hashimoto's
      thyroiditis (HT). Patients and Methods. The study included 46 women with thyroid
      nodules and HT and 60 women with thyroid nodules without HT (controls) who
      underwent a fine needle aspiration biopsy (FNAB). Expression of chemokine
      receptors CXCR3, CCR5, and CRTH2 was assessed by flow cytometry in lymphocytes
      from FNAB samples and from peripheral blood. Results. The percentage of CRTH2+
      lymphocytes was higher in nodules with HT in comparison with controls, both in
      FNAB samples (13.95 versus 6.7%, p = 0.008) and in peripheral blood (6.7 versus
      5.13%, p = 0.047), and positively correlated with serum antibodies to thyroid
      peroxidase (r = 0.243; p = 0.026) and negatively correlated with thyroid volume
      (r = -0.346; p = 0.008). Lymphocytes from neoplastic nodules showed a higher
      expression of both CXCR3 and CCR5 than those from hyperplastic ones. Conclusion.
      Flow cytometry performed in FNAB samples may serve as a good tool in
      investigation of intrathyroidal expression of immunological parameters. In our
      study, the CRTH2 expression on thyroid-infiltrating lymphocytes as well as on
      lymphocytes from peripheral blood was increased in HT as compared to controls.

PMID- 27872868
TI  - Minor Antigen Disparities Impede Induction of Long Lasting Chimerism and
      Tolerance through Bone Marrow Transplantation with Costimulation Blockade.
AB  - Mixed chimerism and tolerance can be successfully induced in rodents through
      allogeneic bone marrow transplantation (BMT) with costimulation blockade (CB),
      but varying success rates have been reported with distinct models and protocols.
      We therefore investigated the impact of minor antigen disparities on the
      induction of mixed chimerism and tolerance. C57BL/6 (H2b) mice received
      nonmyeloablative total body irradiation (3 Gy), costimulation blockade (anti
      CD40L mAb and CTLA4Ig), and 2 * 107 bone marrow cells (BMC) from either of three
      donor strains: Balb/c (H2d) (MHC plus multiple minor histocompatibility antigen
      (mHAg) mismatched), B10.D2 (H2d) or B10.A (H2a) (both MHC mismatched, but mHAg
      matched). Macrochimerism was followed over time by flow cytometry and tolerance
      was tested by skin grafting. 20 of 21 recipients of B10.D2 BMC but only 13 of 18
      of Balb/c BMC and 13 of 20 of B10.A BMC developed stable long-term multilineage
      chimerism (p < 0.05 for each donor strain versus B10.D2). Significantly superior
      donor skin graft survival was observed in successfully established long-term
      chimeras after mHAg matched BMT compared to mHAg mismatched BMT (p < 0.05). Both
      minor and major antigen disparities pose a substantial barrier for the induction
      of chimerism while the maintenance of tolerance after nonmyeloablative BMT and
      costimulation blockade is negatively influenced by minor antigen disparities. .

PMID- 27872867
TI  - Bone Marrow Mesenchymal Stem Cells Enhance the Differentiation of Human Switched
      Memory B Lymphocytes into Plasma Cells in Serum-Free Medium.
AB  - The differentiation of human B lymphocytes into plasma cells is one of the most
      stirring questions with regard to adaptive immunity. However, the terminal
      differentiation and survival of plasma cells are still topics with much to be
      discovered, especially when targeting switched memory B lymphocytes. Plasma cells
      can migrate to the bone marrow in response to a CXCL12 gradient and survive for
      several years while secreting antibodies. In this study, we aimed to get closer
      to niches favoring plasma cell survival. We tested low oxygen concentrations and
      coculture with mesenchymal stem cells (MSC) from human bone marrow. Besides, all
      cultures were performed using an animal protein-free medium. Overall, our model
      enables the generation of high proportions of CD38+CD138+CD31+ plasma cells
      (>=50%) when CD40-activated switched memory B lymphocytes were cultured in direct
      contact with mesenchymal stem cells. In these cultures, the secretion of CXCL12
      and TGF-beta, usually found in the bone marrow, was linked to the presence of
      MSC. The level of oxygen appeared less impactful than the contact with MSC. This
      study shows for the first time that expanded switched memory B lymphocytes can be
      differentiated into plasma cells using exclusively a serum-free medium.

PMID- 27872866
TI  - Roles of Zinc Signaling in the Immune System.
AB  - Zinc (Zn) is an essential micronutrient for basic cell activities such as cell
      growth, differentiation, and survival. Zn deficiency depresses both innate and
      adaptive immune responses. However, the precise physiological mechanisms of the
      Zn-mediated regulation of the immune system have been largely unclear. Zn
      homeostasis is tightly controlled by the coordinated activity of Zn transporters
      and metallothioneins, which regulate the transport, distribution, and storage of
      Zn. There is growing evidence that Zn behaves like a signaling molecule,
      facilitating the transduction of a variety of signaling cascades in response to
      extracellular stimuli. In this review, we highlight the emerging functional roles
      of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and
      immune-related signaling guides the normal development and function of immune
      cells.

PMID- 27872869
TI  - Dynamic association of calcium channel subunits at the cellular membrane.
AB  - High voltage gated calcium channels (VGCCs) are composed of at least three
      subunits, one pore forming [Formula: see text]-subunit, an intracellular
      [Formula: see text]-variant, and a mostly extracellular [Formula: see text]
      variant. Interactions between these subunits determine the kinetic properties of
      VGCCs. It is unclear whether these interactions are stable over time or rather
      transient. Here, we used single-molecule tracking to investigate the surface
      diffusion of [Formula: see text]- and [Formula: see text]-subunits at the cell
      surface. We found that [Formula: see text]-subunits show higher surface mobility
      than [Formula: see text]-subunits, and that they are only transiently confined
      together, suggesting a weak association between [Formula: see text]- and
      [Formula: see text]-subunits. Moreover, we observed that different [Formula: see
      text]-subunits engage in different degrees of association with the [Formula: see
      text]-subunit, revealing the tighter interaction of [Formula: see text] with
      [Formula: see text]. These data indicate a distinct regulation of the [Formula:
      see text] interaction in VGCC subtypes. We modeled their membrane dynamics in a
      Monte Carlo simulation using experimentally determined diffusion constants. Our
      modeling predicts that the ratio of associated [Formula: see text]- and [Formula:
      see text]-subunits mainly depends on their expression density and confinement in
      the membrane. Based on the different motilities of particular [Formula: see text]
      subunit combinations, we propose that their dynamic assembly and disassembly
      represent an important mechanism to regulate the signaling properties of VGCC.

PMID- 27872870
TI  - Nanoscale organization of synaptic adhesion proteins revealed by single-molecule
      localization microscopy.
AB  - The advent of superresolution imaging has created a strong need for both
      optimized labeling strategies and analysis methods to probe the nanoscale
      organization of complex biological structures. We present a thorough description
      of the distribution of synaptic adhesion proteins at the nanoscopic scale, namely
      presynaptic neurexin-[Formula: see text] ([Formula: see text]), and its two
      postsynaptic binding partners neuroligin-1 (Nlg1) and leucine-rich-repeat
      transmembrane protein 2 (LRRTM2). We monitored these proteins in the membrane of
      neurons by direct stochastic optical reconstruction microscopy, after live
      surface labeling with Alexa647-conjugated monomeric streptavidin. The small probe
      ([Formula: see text]) efficiently penetrates into crowded synaptic junctions and
      reduces the distance to target. We quantified the organization of the single
      molecule localization data using a tesselation-based analysis technique. We show
      that Nlg1 exhibits a fairly disperse organization within dendritic spines, while
      LRRTM2 is organized in compact domains, and [Formula: see text] in presynaptic
      terminals displays a dual-organization pattern intermediate between that of Nlg1
      and LRRTM2. These results suggest that part of [Formula: see text] interacts
      transsynaptically with Nlg1 and the other part with LRRTM2.

PMID- 27872871
TI  - Microscopic medical image classification framework via deep learning and shearlet
      transform.
AB  - Cancer is the second leading cause of death in US after cardiovascular disease.
      Image-based computer-aided diagnosis can assist physicians to efficiently
      diagnose cancers in early stages. Existing computer-aided algorithms use hand
      crafted features such as wavelet coefficients, co-occurrence matrix features, and
      recently, histogram of shearlet coefficients for classification of cancerous
      tissues and cells in images. These hand-crafted features often lack
      generalizability since every cancerous tissue and cell has a specific texture,
      structure, and shape. An alternative approach is to use convolutional neural
      networks (CNNs) to learn the most appropriate feature abstractions directly from
      the data and handle the limitations of hand-crafted features. A framework for
      breast cancer detection and prostate Gleason grading using CNN trained on images
      along with the magnitude and phase of shearlet coefficients is presented.
      Particularly, we apply shearlet transform on images and extract the magnitude and
      phase of shearlet coefficients. Then we feed shearlet features along with the
      original images to our CNN consisting of multiple layers of convolution, max
      pooling, and fully connected layers. Our experiments show that using the
      magnitude and phase of shearlet coefficients as extra information to the network
      can improve the accuracy of detection and generalize better compared to the state
      of-the-art methods that rely on hand-crafted features. This study expands the
      application of deep neural networks into the field of medical image analysis,
      which is a difficult domain considering the limited medical data available for
      such analysis.

PMID- 27872872
TI  - Quantitative analysis of hypertrophic myocardium using diffusion tensor magnetic
      resonance imaging.
AB  - Systemic hypertension is a causative factor in left ventricular hypertrophy
      (LVH). This study is motivated by the potential to reverse or manage the
      dysfunction associated with structural remodeling of the myocardium in this
      pathology. Using diffusion tensor magnetic resonance imaging, we present an
      analysis of myocardial fiber and laminar sheet orientation in ex vivo
      hypertrophic (6 SHR) and normal (5 WKY) rat hearts using the covariance of the
      diffusion tensor. First, an atlas of normal cardiac microstructure was formed
      using the WKY b0 images. Then, the SHR and WKY b0 hearts were registered to the
      atlas. The acquired deformation fields were applied to the SHR and WKY heart
      tensor fields followed by the preservation of principal direction (PPD)
      reorientation strategy. A mean tensor field was then formed from the registered
      WKY tensor images. Calculating the covariance of the registered tensor images
      about this mean for each heart, the hypertrophic myocardium exhibited
      significantly increased myocardial fiber derangement ([Formula: see text]) with a
      mean dispersion of 38.7 deg, and an increased dispersion of the laminar sheet
      normal ([Formula: see text]) of 54.8 deg compared with 34.8 deg and 51.8 deg,
      respectively, in the normal hearts. Results demonstrate significantly altered
      myocardial fiber and laminar sheet structure in rats with hypertensive LVH.

PMID- 27872874
TI  - Preterm neonatal lateral ventricle volume from three-dimensional ultrasound is
      not strongly correlated to two-dimensional ultrasound measurements.
AB  - The aim of this study is to compare longitudinal two-dimensional (2-D) and three
      dimensional (3-D) ultrasound (US) estimates of ventricle size in preterm neonates
      with posthemorrhagic ventricular dilatation (PHVD) using quantitative
      measurements of the lateral ventricles. Cranial 2-D US and 3-D US images were
      acquired from neonatal patients with diagnosed PHVD within 10 min of each other
      one to two times per week and analyzed offline. Ventricle index, anterior horn
      width, third ventricle width, and thalamo-occipital distance were measured on the
      2-D images and ventricle volume (VV) was measured from 3-D US images. Changes in
      the measurements between successive image sets were also recorded. No strong
      correlations were found between VV and 2-D US measurements ([Formula: see text]
      between 0.69 and 0.36). Additionally, weak correlations were found between
      changes in 2-D US measurements and 3-D US VV ([Formula: see text] between 0.13
      and 0.02). A trend was found between increasing 2-D US measurements and 3-D US
      based VV, but this was not the case when comparing changes between 3-D US VV and
      2-D US measurements. If 3-D US-based VV provides a more accurate estimate of
      ventricle size than 2-D US measurements, moderate-weak correlations with 3-D US
      suggest that monitoring preterm patients with PHVD using 2-D US measurements
      alone might not accurately represent whether the ventricles are progressively
      dilating. A volumetric measure (3-D US or MRI) could be used instead to more
      accurately represent changes.

PMID- 27872873
TI  - Postediting prostate magnetic resonance imaging segmentation consistency and
      operator time using manual and computer-assisted segmentation: multiobserver
      study.
AB  - Prostate segmentation on T2w MRI is important for several diagnostic and
      therapeutic procedures for prostate cancer. Manual segmentation is time
      consuming, labor-intensive, and subject to high interobserver variability. This
      study investigated the suitability of computer-assisted segmentation algorithms
      for clinical translation, based on measurements of interoperator variability and
      measurements of the editing time required to yield clinically acceptable
      segmentations. A multioperator pilot study was performed under three pre- and
      postediting conditions: manual, semiautomatic, and automatic segmentation. We
      recorded the required editing time for each segmentation and measured the editing
      magnitude based on five different spatial metrics. We recorded average editing
      times of 213, 328, and 393 s for manual, semiautomatic, and automatic
      segmentation respectively, while an average fully manual segmentation time of 564
      s was recorded. The reduced measured postediting interoperator variability of
      semiautomatic and automatic segmentations compared to the manual approach
      indicates the potential of computer-assisted segmentation for generating a
      clinically acceptable segmentation faster with higher consistency. The lack of
      strong correlation between editing time and the values of typically used error
      metrics ([Formula: see text]) implies that the necessary postsegmentation editing
      time needs to be measured directly in order to evaluate an algorithm's
      suitability for clinical translation.

PMID- 27872876
TI  - Dataset of plasmid DNA extraction using different magnetic nanoparticles (MNPs).
AB  - In this dataset we integrated figures related to bacterial transformation using
      pBI121 plasmid and complementary analysis for magnetic nanoparticles (MNPs)
      characterizations. The structural map of pBI121 plasmid was drawn by Vector NTI
      software using the complete sequence of binary vector pBI121. Escherichia coli
      bacteria transformed using pBI121 plasmid and were grown on the selection media
      containing kanamycin. MNPs were characterized by energy dispersive spectroscopy
      (EDS) and transmission electron microscopy (TEM). Finally, the overall efficiency
      of different MNPs (Fe3O4, Fe3O4/SiO2, Fe3O4/SiO2/TiO2) in plasmid DNA isolation
      was compared using gel electrophoresis analysis. The data supplied in this
      article supports the accompanying publication "Comparative study of three
      magnetic nano-particles (FeSO4, FeSO4/SiO2, FeSO4/SiO2/TiO2) in plasmid DNA
      extraction" (H. Rahnama, A. Sattarzadeh, F. Kazemi, N. Ahmadi, F. Sanjarian, Z.
      Zand, 2016) [1].

PMID- 27872875
TI  - A comparison of the innate flexibilities of six chains in F1-ATPase with
      identical secondary and tertiary folds; 3 active enzymes and 3 structural
      proteins.
AB  - The alpha and beta subunits comprising the hexameric assembly of F1-ATPase share
      a high degree of structural identity, though low primary identity. Each subunit
      binds nucleotide in similar pockets, yet only beta subunits are catalytically
      active. Why? We re-examine their internal symmetry axes and observe interesting
      differences. Dividing each chain into an N-terminal head region, a C-terminal
      foot region, and a central torso, we observe (1) that while the foot and head
      regions in all chains obtain high and similar mobility, the torsos obtain
      different mobility profiles, with the beta subunits exhibiting a higher motility
      compared to the alpha subunits, a trend supported by the crystallographic B
      factors. The beta subunits have greater torso mobility by having fewer
      distributed, nonlocal packing interactions providing a spacious and soft
      connectivity and offsetting the resultant softness with local stiffness elements,
      including an additional beta sheet. (2) A loop near the nucleotide binding-domain
      of the beta subunits, absent in the alpha subunits, swings to create a large
      variation in the occlusion of the nucleotide binding region. (3) A combination of
      the softest three eigenmodes significantly reduces the root mean square
      difference between the open and closed conformations of the beta subunits. (4)
      Comparisons of computed and observed crystallographic B-factors suggest a
      suppression of a particular symmetry axis in an alpha subunit. (5) Unexpectedly,
      the soft intra-monomer oscillations pertain to distortions that do not create
      inter-monomer steric clashes in the assembly, suggesting that structural
      optimization of the assembly evolved at all levels of complexity.

PMID- 27872877
TI  - Data on spermatogenesis in rat males gestationally exposed to bisphenol A and
      high fat diets.
AB  - This data article contains supporting information regarding the research article
      entitled "High butter-fat diet and bisphenol A additively impair male rat
      spermatogenesis" (P. Tarapore, M. Hennessy, D. Song, J. Ying, B. Ouyang, V.
      Govindarajah, et al.,) [1]. Sprague-Dawley females were fed AIN, high fat butter,
      17alpha-ethinyl estradiol, or high fat butter plus four bisphenol A doses (2500
      ug/kg bw-d, 250 ug/kg bw-d, 25 ug/kg bw-d, and 2.5 ug/kg bw-d) before and during
      pregnancy. All diets were switched to AIN after the pups were born. Male
      offspring received testosterone (T)- and estradiol-17beta (E2)-filled implants
      from postnatal day 70-210 for 20 weeks (T+E2 rat model). The testes were weighed,
      and examined for impairments in spermatogenesis.

PMID- 27872878
TI  - Serum antioxidant capacity and peroxide level of seven healthy subjects after
      consumption of different foods.
AB  - This article reports experimental data related to the research article entitled
      "Different effectiveness of two pastas supplemented with either lipophilic or
      hydrophilic/phenolic antioxidants in affecting serum as evaluated by the novel
      Antioxidant/Oxidant Balance approach" (M.N. Laus, M. Soccio, M. Alfarano, A.
      Pasqualone, M.S. Lenucci, G. Di Miceli, D. Pastore, 2016) [1]. Antioxidant status
      of blood serum of seven healthy subjects was evaluated during four hours after
      consumption of two functional pastas, supplemented with either bran oleoresin or
      bran water extract obtained from durum wheat. For comparison, the effect of a non
      supplemented reference pasta was also evaluated, as well as the effects of
      glucose, of the wheat grain dietary supplement Lisosan G, and of the reference
      pasta consumed together with Lisosan G. Serum antioxidant status was evaluated by
      measuring both the serum antioxidant capacity, using LOX-FL, ORAC and TEAC
      methods, and the serum oxidant status, assessed as peroxide level.

PMID- 27872879
TI  - Data on Fe (II) biosorption onto Sargassum hystrix algae obtained from the
      Persian Gulf in Bushehr Port, Iran.
AB  - In this article, we used Sargassum hystrix algae as biosorbent for removal of Fe
      (II) from aqueous solutions that was collected along the Persian Gulf coastline,
      Bushehr, Iran. The concentration level of remaining Fe (II) in the samples was
      measured by using flame atomic absorption spectrometry (FAAS, Varian AA240,
      Australia). The isotherms, kinetics and modeling data of Fe (II) biosorption onto
      Sargassum hystrix were also presented.

PMID- 27872880
TI  - Data on quantification of signaling pathways activated by KIT and PDGFRA mutants.
AB  - The present data are related to the article entitled "Insights into ligand
      stimulation effects on gastro-intestinal stromal tumors signaling" (C. Bahlawane,
      M. Schmitz, E. Letellier, K. Arumugam, N. Nicot, P.V. Nazarov, S. Haan, 2016)
      [1]. Constitutive and ligand-derived signaling pathways mediated by KIT and
      PDGFRA mutated proteins found in gastrointestinal stromal tumors (GIST) were
      compared. Expression of mutant proteins was induced by doxycycline in an isogenic
      background (Hek293 cells). Kit was identified by FACS at the cell surface and
      found to be quickly degraded or internalized upon SCF stimulation for both Kit
      Wild type and Kit mutant counterparts. Investigation of the main activated
      pathways in GIST unraveled a new feature specific for oncogenic KIT mutants,
      namely their ability to be further activated by Kit ligand, the stem cell factor
      (scf). We were also able to identify the MAPK pathway as the most prominent
      target for a common inhibition of PDGFRA and KIT oncogenic signaling. Western
      blotting and micro-array analysis were applied to analyze the capacities of the
      mutant to induce an effective STATs response. Among all Kit mutants, only Kit
      Ex11 deletion mutant was able to elicit an effective STATs response whereas all
      PDGFRA were able to do so.

PMID- 27872881
TI  - Infodemiological data of West-Nile virus disease in Italy in the study period
      2004-2015.
AB  - Google Trends (GT) was mined from 2004 to 2015, searching for West-Nile virus
      disease (WNVD) in Italy. GT-generated data were modeled as a time series and were
      analyzed using classical time series analyses. In particular, correlation between
      GT-based Relative Search Volumes (RSVs) related to WNVD and "real-world"
      epidemiological cases in the same study period resulted r=0.76 (p<0.0001) on a
      monthly basis and r=0.80 (p<0.0001) on a yearly basis. The partial
      autocorrelation analysis and the spectral analysis confirmed that a 1-year
      regular pattern could be detected. Correlation between GT-based RSVs related to
      WNVD yielded a r=0.54 (p<0.05) on a regional basis. Summarizing, GT-generated
      data concerning WNVD well correlated with epidemiology and could be exploited for
      complementing traditional surveillance.

PMID- 27872882
TI  - Data of cost-optimal solutions and retrofit design methods for school renovation
      in a warm climate.
AB  - "Efficient Solutions and Cost-Optimal Analysis for Existing School Buildings"
      (Paolo Maria Congedo, Delia D'Agostino, Cristina Baglivo, Giuliano Tornese,
      Ilaria Zaca) [1] is the paper that refers to this article. It reports the data
      related to the establishment of several variants of energy efficient retrofit
      measures selected for two existing school buildings located in the Mediterranean
      area. In compliance with the cost-optimal analysis described in the Energy
      Performance of Buildings Directive and its guidelines (EU, Directive, EU 244,)
      [2], [3], these data are useful for the integration of renewable energy sources
      and high performance technical systems for school renovation. The data of cost
      efficient high performance solutions are provided in tables that are explained
      within the following sections. The data focus on the describe school
      refurbishment sector to which European policies and investments are directed. A
      methodological approach already used in previous studies about new buildings is
      followed (Baglivo Cristina, Congedo Paolo Maria, D'Agostino Delia, Zaca Ilaria,
      2015; IlariaZaca, Delia D'Agostino, Paolo Maria Congedo, Cristina Baglivo;
      Baglivo Cristina, Congedo Paolo Maria, D'Agostino Delia, Zaca Ilaria, 2015;
      Ilaria Zaca, Delia D'Agostino, Paolo Maria Congedo, Cristina Baglivo, 2015; Paolo
      Maria Congedo, Cristina Baglivo, IlariaZaca, Delia D'Agostino,2015) [4], [5],
      [6], [7], [8]. The files give the cost-optimal solutions for a kindergarten
      (REF1) and a nursery (REF2) school located in Sanarica and Squinzano (province of
      Lecce Southern Italy). The two reference buildings differ for construction
      period, materials and systems. The eleven tables provided contain data about the
      localization of the buildings, geometrical features and thermal properties of the
      envelope, as well as the energy efficiency measures related to walls, windows,
      heating, cooling, dhw and renewables. Output values of energy consumption, gas
      emission and costs are given for a financial and a macro-economic analysis. This
      data article provides 288 and 96 combinations for REF1 and REF2, respectively.
      The output values are obtained using the software ProCasaClima 2015v.2.0.

PMID- 27872883
TI  - Model fitting data from syllogistic reasoning experiments.
AB  - The data presented in this article are related to the research article entitled
      "Probabilistic representation in syllogistic reasoning: A theory to integrate
      mental models and heuristics" (M. Hattori, 2016) [1]. This article presents
      predicted data by three signature probabilistic models of syllogistic reasoning
      and model fitting results for each of a total of 12 experiments (N=404) in the
      literature. Models are implemented in R, and their source code is also provided.

PMID- 27872884
TI  - Data on clinical characteristics of a heart failure patients' cohort with reduced
      ejection fraction and analysis of the circulating values of five different heart
      failure biomarkers; high sensitivity troponin T, galectin-3, C-terminal
      propeptide of type I procollagen, soluble AXL and BNP.
AB  - In this article, the full description of a heart failure with reduced ejection
      fraction (HF_REF) cohort of 192 patients is provided. Tables with the baseline
      demographic, prior history, ECG parameters, echocardiographic parameters,
      laboratory values and pharmacological treatment of these patients are included.
      Also, the quartile values of the analyzed circulating biomarkers: high
      sensitivity Troponin T (hs-TnT), galectin-3 (Gal-3), C-terminal propeptide of
      type I procollagen (CICP), soluble AXL (sAXL) and Brain Natriuretic Peptide (BNP)
      are given. The main demographic and clinical features of the patients' subgroups
      that have hs-TnT, Gal-3, CICP or BNP above the third quartile are described.
      Tables with Pearson correlation analysis of the HF_REF patients' biomarker levels
      are included. And Pearson correlation analysis of the HF_REF patients' hs-TnT,
      Gal-3, CICP levels with patients' biochemical parameters, blood count and
      inflammation parameters are also described. These data are related to the
      research articles (AXL receptor tyrosine kinase is increased in patients with
      heart failure (M. Batlle, P. Recarte-Pelz, E. Roig, M.A. Castel, M. Cardona, M.
      Farrero, et al., 2014) [1] and Use of serum levels of high sensitivity troponin
      T, galectin-3 and C-terminal propeptide of type I procollagen at long term follow
      up in Heart Failure patients with reduced ejection fraction: comparison with
      soluble AXL and BNP (M. Batlle, B. Campos, M. Farrero, M. Cardona, B. Gonzalez,
      M.A. Castel, et al., 2016) [2].

PMID- 27872885
TI  - Data comparing the kinetics of procollagen type I processing by bone
      morphogenetic protein 1 (BMP-1) with and without procollagen C-proteinase
      enhancer 1 (PCPE-1).
AB  - This article provides kinetic constants for C-terminal processing of procollagen
      type I by bone morphogenetic protein 1 (BMP-1; the major procollagen C
      proteinase), a reaction stimulated by the connective tissue glycoprotein
      procollagen C-proteinase enhancer 1 (PCPE-1). Reported are Km , Vmax , Kcat and
      Kcat /Km (catalytic coefficient) values for BMP-1 alone, BMP-1 with intact PCPE
      1, BMP-1 with the CUB (Complement C1r/C1s, Uegf, BMP-1) domains fragment of PCPE
      1 as well as its NTR (netrin-like) domain.

PMID- 27872886
TI  - Data set of Aspergillus flavus induced alterations in tear proteome:
      Understanding the pathogen-induced host response to fungal infection.
AB  - Fungal keratitis is one of the leading causes of blindness in the tropical
      countries affecting individuals in their most productive age. The host immune
      response during this infection is poorly understood. We carried out comparative
      tear proteome analysis of Aspergillus flavus keratitis patients and uninfected
      controls. Proteome was separated into glycosylated and non-glycosylated fractions
      using lectin column chromatography before mass spectrometry. The data revealed
      the major processes activated in the human host in response to fungal infection
      and reflected in the tear. Extended analysis of this dataset presented here
      complements the research article entitled "Aspergillus flavus induced alterations
      in tear protein profile reveal pathogen-induced host response to fungal infection
      [1]" (Jeyalakhsmi Kandhavelu, Naveen Luke Demonte, Venkatesh Prajna
      Namperumalsamy, Lalitha Prajna, Chitra Thangavel, Jeya Maheshwari Jayapal,
      Dharmalingam Kuppamuthu, 2016). The mass spectrometry proteomics data have been
      deposited in the ProteomeXchange Consortium via the PRIDE partner repository with
      the dataset identifier PRIDE:PXD003825.

PMID- 27872887
TI  - Mapping cycling patterns and trends using Strava Metro data in the city of
      Johannesburg, South Africa.
AB  - Plans for smart mobility through cycling are often hampered by lack of
      information on cycling patterns and trends, particularly in cities of the
      developing world such as Johannesburg. Similarly, traditional methods of data
      collection such as bicycle counts are often expensive, cover a limited spatial
      extent and not up-to-date. Consequently, the dataset presented in this paper
      illustrates the spatial and temporal coverage of cycling patterns and trends in
      Johannesburg for the year 2014 derived from the geolocation based mobile
      application Strava. To the best knowledge of the authors, there is little or no
      comprehensive dataset that describes cycling patterns in Johannesburg. Perhaps
      this dataset is a tool that will support evidence based transportation planning
      and smart mobility.

PMID- 27872888
TI  - Newly listed firms' M&A activities data and their VC-backing data.
AB  - This article contains hand collected and matched data on the VC investment
      situation in newly listed firms in SME and ChiNext board from 2009 to 2012 and
      the corresponding M&A activities data undertaken by these newly listed firms as
      acquirers in three years following initial public offering. Mentioned data are
      related to the research article "Heterogeneous Venture Capital, M&A Activity, and
      Market Response" (W. Li, T. Cao, Z. Feng, 2016) [1].

PMID- 27872889
TI  - Commentary on "A new drug with a nasty bite: A case of krokodil-induced skin
      necrosis in an intravenous drug user".

PMID- 27872890
TI  - Koebner phenomenon in pemphigus vulgaris patients.

PMID- 27872891
TI  - Dengue with a morbilliform rash and a positive tourniquet test.

PMID- 27872892
TI  - Reply to: "Commentary on 'A new drug with a nasty bite: A case of krokodil
      induced skin necrosis in an intravenous drug user'".

PMID- 27872894
TI  - Perspective from the Alzheimer's Association: Neuroimaging Professional Interest
      Area of ISTAART continues impact on the field.

PMID- 27872895
TI  - The Alzheimer's Imaging Consortium: Celebrating 20 years of creativity and
      progress.

PMID- 27872893
TI  - Response to sunitinib (Sutent) in chemotherapy refractory clear cell ovarian
      cancer.
AB  - *Case describes a response to sunitinib in clear cell ovarian cancer.*Discussion
      of unique molecular characteristics of clear cell ovarian cancers*Practical
      points regarding dosing and toxicity when using sunitinib discussed.

PMID- 27872897
TI  - Physiotherapy Practice Patterns for Management of Patients Undergoing Thoracic
      Surgeries in India: A Survey.
AB  - Aim. The aim of the current study is to determine the practice patterns of
      physiotherapists for patients undergoing thoracic surgeries in India. Materials
      and Methodology. A cross-sectional survey was conducted across India in which 600
      questionnaires were sent in emails to physiotherapists. The questionnaire
      addressed assessment and treatment techniques of thoracic surgery. Results. A
      total of 234 completed questionnaires were returned with a response rate of 39%,
      with the majority of responses received from Telangana, Karnataka, and Andhra
      Pradesh. More than 90% of the responders practiced physical examination, chest
      expansion, chest X-ray, ABG analysis, pulmonary function test, and SpO2 (oxygen
      saturation) as the assessment measures in both the pre- and the postoperative
      phase. Breathing exercises, incentive spirometry, thoracic expansion exercises,
      coughing and huffing, positioning, and modified postural drainage are found to be
      commonly used physiotherapy interventions, both pre- and postoperatively, with a
      response rate of more than 90%. A response rate of more than 84.6% indicated that
      patients are made to dangle their lower limbs over the edge of the bed on the 1st
      postoperative day. Mobilization, such as walking up to a chair, sit to stand
      exercises, and perambulation within the patient's room, was started on the 2nd
      postoperative day, as stated by more than 65% of the physiotherapists. Staircase
      climbing was started on the 5th postoperative day. The most commonly used
      functional evaluation prior to discharge was 6-minute walk test. This was, in
      fact, practiced by 77.4% of the physiotherapists in their clinical settings.
      Conclusion. The most predominantly employed assessment measures included were
      physical examination, chest expansion, ABG analysis, pulmonary function test,
      chest X-ray, SpO2 (oxygen saturation), peripheral muscle strength, and
      cardiopulmonary exercise. The physiotherapy interventions most commonly used were
      breathing exercises, thoracic expansion exercises, incentive spirometry, and
      coughing and huffing techniques, in both the pre- and the postoperative phase.

PMID- 27872898
TI  - The Impact of Variable Wind Shear Coefficients on Risk Reduction of Wind Energy
      Projects.
AB  - Estimation of wind speed at proposed hub heights is typically achieved using a
      wind shear exponent or wind shear coefficient (WSC), variation in wind speed as a
      function of height. The WSC is subject to temporal variation at low and high
      frequencies, ranging from diurnal and seasonal variations to disturbance caused
      by weather patterns; however, in many cases, it is assumed that the WSC remains
      constant. This assumption creates significant error in resource assessment,
      increasing uncertainty in projects and potentially significantly impacting the
      ability to control gird connected wind generators. This paper contributes to the
      body of knowledge relating to the evaluation and assessment of wind speed, with
      particular emphasis on the development of techniques to improve the accuracy of
      estimated wind speed above measurement height. It presents an evaluation of the
      use of a variable wind shear coefficient methodology based on a distribution of
      wind shear coefficients which have been implemented in real time. The results
      indicate that a VWSC provides a more accurate estimate of wind at hub height,
      ranging from 41% to 4% reduction in root mean squared error (RMSE) between
      predicted and actual wind speeds when using a variable wind shear coefficient at
      heights ranging from 33% to 100% above the highest actual wind measurement.

PMID- 27872896
TI  - Comparison of Clinical and Radiologic Outcome of Adolescent Idiopathic Scoliosis
      Treated with Hybrid Hook-Screw Instrumentation versus Universal Clamp System.
AB  - Background. In surgical treatment of adolescent idiopathic scoliosis (AIS),
      hybrid universal clamp system has been used by some authors. We aimed to compare
      the clinical and radiologic outcome of hybrid universal clamp with hybrid
      thoracic hook lumbar screw. Methods. A prospective study was performed on 56
      consecutive patients with AIS, who had alternatively undergone a posterior spinal
      fusion and instrumentation with hybrid thoracic hook lumbar screw system (28
      patients: group A) and hybrid universal clamp system (28 patients: group B)
      between June 2006 and January 2014 at Imam Reza University Hospital and had been
      followed up for more than two years. The comparison was according to radiographic
      changes, operative time, intraoperative blood loss, complications, and Scoliosis
      Research Society (SRS-22) outcome scores. Results. The preoperative mean curve
      Cobb angle was 58 degrees  +/- 7 degrees  (42 degrees -74 degrees ) in group A
      and 60 degrees  +/- 9 degrees  (46 degrees -75 degrees ) in group B. The mean
      final coronal curve correction was 60.4% and 75.5% in groups A and B,
      respectively (P = 0.001). Postoperative SRS outcome scores were also comparable.
      Conclusion. Universal clamp instrumentation had a significantly better curve
      correction and lower complication rate compared with hybrid thoracic hook lumbar
      screw. Both instrumentation methods had similar operative time, intraoperative
      blood loss, and postoperative SRS outcome scores.

PMID- 27872899
TI  - De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy.
AB  - OBJECTIVE: We describe 2 additional patients with early-onset epilepsy with a de
      novo FGF12 mutation. METHODS: Whole-exome sequencing was performed in 2 unrelated
      patients with early-onset epilepsy and their unaffected parents. Genetic variants
      were assessed by comparative trio analysis. Clinical evolution, EEG, and
      neuroimaging are described. The phenotype and response to treatment was reviewed
      and compared to affected siblings in the original report. RESULTS: We identified
      the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2
      additional patients with early-onset epilepsy. Similar to the original brothers
      described, both presented with tonic seizures in the first month of life. In the
      first patient, seizures responded to sodium channel blockers and her development
      was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant
      focal epilepsy, moderate intellectual disability, and autism. Carbamazepine
      (sodium channel blocker) was tried later in her course but not continued due to
      an allergic reaction. CONCLUSIONS: The identification of a recurrent de novo
      mutation in 2 additional unrelated probands with early-onset epilepsy supports
      the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented
      with similar early clinical phenotypes; however, this report expands the
      phenotype associated with this mutation which contrasts with the progressive
      course and early mortality of the siblings in the original report.

PMID- 27872900
TI  - Robot-Assisted Laparoscopic Renal Schwannoma Excision.
AB  - Background: To report the first case of a renal schwannoma excised with robot
      assisted laparoscopy. Case Presentation: A 43-year-old Caucasian female patient
      with vague abdominal symptoms was noted to have incidental right renal mass.
      Physical examination and laboratory tests were within normal limits. CT revealed
      a 4.6 cm heterogeneous enhancing right renal mass arising near the hilum. RENAL
      nephrometry score was 11a. She was treated by right robot-assisted laparoscopic
      nephrectomy. She recovered well without complications. Pathology analysis
      revealed a benign renal schwannoma. Conclusion: Renal schwannoma is a rare kidney
      tumor. We report the first known case of this tumor excised by robot-assisted
      laparoscopic nephrectomy.

PMID- 27872901
TI  - Reperfusion and Compartment Syndrome After Flexible Ureteroscopy in a Patient
      with an Iliac Vascular Graft.
AB  - Background: Flexible ureteroscopy (fURS) is one of the main treatment options for
      urolithiasis less than 2 cm. Although fURS has no relative contraindication, some
      anatomical factors may need to be considered, as not all patients are suitable
      for the regular lithotomy position (LP). We report the case of a patient with a
      right iliac vascular graft that after an fURS without intraoperative incidences
      developed a reperfusion syndrome of the right lower limb. Case Presentation: A 46
      year-old male patient was referred for treatment and follow-up in the cystinuric
      clinic after being found to have a 3 cm pelvic stone with a Double-J catheter in
      place after two failed sessions of shockwave lithotripsy. The patient was placed
      in the LP and a standard ureteroscopy was done with no intraoperative
      complications. During the first hour in the recovery room, the patient developed
      severe pain in the right calf muscle stiffness, edema, and increased volume. A
      postreperfusion and compartment syndrome diagnosis was made with emergency
      fasciotomy. Conclusion: To perform fURS, each case must be assessed individually.
      If a patient with an iliac vascular graft has to undergo fURS, the patient
      positioning must be modified by keeping the ipsilateral (or both) legs straight
      to avoid graft complications.

PMID- 27872902
TI  - Wind energy potential assessment of Cameroon's coastal regions for the
      installation of an onshore wind farm.
AB  - For the future installation of a wind farm in Cameroon, the wind energy
      potentials of three of Cameroon's coastal cities (Kribi, Douala and Limbe) are
      assessed using NASA average monthly wind data for 31 years (1983-2013) and
      compared through Weibull statistics. The Weibull parameters are estimated by the
      method of maximum likelihood, the mean power densities, the maximum energy
      carrying wind speeds and the most probable wind speeds are also calculated and
      compared over these three cities. Finally, the cumulative wind speed
      distributions over the wet and dry seasons are also analyzed. The results show
      that the shape and scale parameters for Kribi, Douala and Limbe are 2.9 and 2.8,
      3.9 and 1.8 and 3.08 and 2.58, respectively. The mean power densities through
      Weibull analysis for Kribi, Douala and Limbe are 33.7 W/m2, 8.0 W/m2 and 25.42
      W/m2, respectively. Kribi's most probable wind speed and maximum energy carrying
      wind speed was found to be 2.42 m/s and 3.35 m/s, 2.27 m/s and 3.03 m/s for Limbe
      and 1.67 m/s and 2.0 m/s for Douala, respectively. Analysis of the wind speed and
      hence power distribution over the wet and dry seasons shows that in the wet
      season, August is the windiest month for Douala and Limbe while September is the
      windiest month for Kribi while in the dry season, March is the windiest month for
      Douala and Limbe while February is the windiest month for Kribi. In terms of mean
      power density, most probable wind speed and wind speed carrying maximum energy,
      Kribi shows to be the best site for the installation of a wind farm. Generally,
      the wind speeds at all three locations seem quite low, average wind speeds of all
      the three studied locations fall below 4.0m/s which is far below the cut-in wind
      speed of many modern wind turbines. However we recommend the use of low cut-in
      speed wind turbines like the Savonius for stand alone low energy needs.

PMID- 27872903
TI  - Energy behavior on side structure in event of ship collision subjected to
      external parameters.
AB  - The safety of ships in regards to collisions and groundings, as well as the
      navigational and structural aspects of ships, has been improved and developed up
      to this day by technical, administrative and nautical parties. The damage
      resulting from collisions could be reduced through several techniques such as
      designing appropriate hull structures, ensuring tightness of cargo tanks as well
      as observation and review on structural behaviors, whilst accounting for all
      involved parameters. The position during a collision can be influenced by the
      collisions' location and angle as these parts are included in the external
      dynamics of ship collisions. In this paper, the results of several collision
      analyses using the finite element method were used and reviewed regarding the
      effect of location and angle on energy characteristic. Firstly, the capabilities
      of the structure and its ability to resist destruction in a collision process
      were presented and comparisons were made to other collision cases. Three types of
      collisions were identified based on the relative location of contact points to
      each other. From the results, it was found that the estimation of internal energy
      by the damaged ships differed in range from 12%-24%. In the second stage, the
      results showed that a collision between 30 to 60 degrees produced higher level
      energy than a collision in the perpendicular position. Furthermore, it was
      concluded that striking and struck objects in collision contributed to energy and
      damage shape.

PMID- 27872904
TI  - Exploring informed consent in HIV clinical trials: A case study in Uganda.
AB  - INTRODUCTION: In settings with low literacy levels ensuring that participants are
      fully-informed before they consent to participate in clinical trials is a
      challenge. We explored the experiences and concerns of key actors in the informed
      consent process in two HIV clinical trials. METHOD: Semi-structured interviews
      were conducted with 46 respondents including trial participants, research study
      team and research ethics committee members about their experiences during the
      informed consent process. Three focus group discussions were conducted with 14
      Community Advisory Board (CAB) members and 17 trial participants. Data were
      analysed to identify key themes. FINDINGS: The consent process was highlighted as
      an important procedure by all the key actors however each group had a particular
      area of emphasis. Signing a consent form was given importance by research team
      and ethics committee members, because it provided documented evidence of a
      participant's willingness to join a clinical trial. Participants did not welcome
      the presence of a witness for a non-literate participant because understanding
      study information was not closely related to an ability to read and write.
      CONCLUSION: This study's findings indicated that obtaining a volunteer's
      signature or thumbprint on a consent form did not necessarily mean that the
      participant was fully-informed about the information relevant to their taking
      part nor that they understood all the information shared with them. Informed
      consent requires sufficient time in the research process to have staff trained
      well enough before research begins. Ensuring and gaining informed consent should
      be understood and treated as a relation-centred, dynamic supportive process
      throughout the duration of a research study.

PMID- 27872906
TI  - Sequence-specific recognition of methylated DNA by an engineered transcription
      activator-like effector protein.
AB  - A 5mC-selective TALE-repeat was created by screening a TALE repeat library
      containing randomized amino acids at repeat variable diresidues and their
      neighboring residues. The new repeat showed high 5mC discrimination ability. An
      artificial TALE containing the new repeat activated an endogenous gene in a
      genomic methylation status-dependent manner.

PMID- 27872912
TI  - Chirality sensing and discrimination of lysine derivatives in water with a
      dyn[4]arene.
AB  - The asymmetric deformation of a dyn[4]arene upon the binding of various lysine
      derivatives leads to distinct induced circular dichroism outputs in buffered
      water, which can be exploited not only for the determination of their
      enantiomeric excesses, but also for their classification by linear discriminant
      analysis.

PMID- 27872913
TI  - Direct synthesis of ethanol via CO2 hydrogenation using supported gold catalysts.
AB  - An efficient titania supported Au nanocluster (NC) has been prepared for the
      direct synthesis of useful EtOH from CO2 and H2. The unique creation of an
      excellent synergistic effect between Au NCs and the underlying TiO2 support,
      especially the anatase crystal phase with abundant oxygen vacancies, can achieve
      the high performance for EtOH synthesis under moderate and practical conditions.

PMID- 27872914
TI  - The role of water in the synthesis of indium nanoparticles.
AB  - We report the water-assisted synthesis of indium nanoparticles (In NPs). We found
      that a precise amount of water was necessary to allow the formation of the
      desired 7 nm In NPs: the oxidation of the In surface by water inhibits the growth
      of NPs as well as subsequent reactivity with white phosphorus (P4). A novel
      surface activation method based on the use of organosilanes is presented.

PMID- 27872915
TI  - Silica core/conjugated polymer shell particles via seeded Knoevenagel dispersion
      polymerization - laser action in whispering gallery mode resonators.
AB  - Here, we present a seeded Knoevenagel dispersion polymerization to generate
      hybrid particles with a conjugated polymer shell on inorganic silica cores. This
      seeded dispersion polymerization facilitates the generation of core-shell
      particles, which exhibit whispering gallery mode lasing. The lasing threshold
      decreases while the spectral range of emission increases with increasing shell
      thickness. This novel seeded Knoevenagel dispersion polymerization opens up a
      facile and metal free pathway towards single particle conjugated polymer lasers
      on the micrometer scale.

PMID- 27872905
TI  - Interferon-driven deletion of antiviral B cells at the onset of chronic
      infection.
AB  - Inadequate antibody responses and perturbed B cell compartments represent
      hallmarks of persistent microbial infections, but the mechanisms whereby
      persisting pathogens suppress humoral immunity remain poorly defined. Using
      adoptive transfer experiments in the context of a chronic lymphocytic
      choriomeningitis virus (LCMV) infection of mice, we have documented rapid
      depletion of virus-specific B cells that coincided with the early type I
      interferon response to infection. We found that the loss of activated B cells was
      driven by type I interferon (IFN-I) signaling to several cell types including
      dendritic cells, T cells and myeloid cells. Intriguingly, this process was
      independent of B cell-intrinsic IFN-I sensing and resulted from biased
      differentiation of naive B cells into short-lived antibody-secreting cells. The
      ability to generate robust B cell responses was restored upon IFN-I receptor
      blockade or, partially, when experimentally depleting myeloid cells or the IFN-I
      induced cytokines interleukin 10 and tumor necrosis factor alpha. We have termed
      this IFN-I-driven depletion of B cells "B cell decimation". Strategies to counter
      "B cell decimation" should thus help us better leverage humoral immunity in the
      combat against persistent microbial diseases.

PMID- 27872916
TI  - Reversible pH-independent optical potassium sensor with lipophilic solvatochromic
      dye transducer on surface modified microporous nylon.
AB  - A reversible and pH-independent fluorescent ion optode is introduced with an
      ionophore and surface confined solvatochromic dye transducer doped onto
      microporous nylon membranes. The resulting film responds to K+ with excellent
      selectivity over the range of 10-7 to 10-2 M and a response time of t95 < 60 s
      above 10-6 M.

PMID- 27872918
TI  - Distance mediated electrochemiluminescence enhancement of CdS thin films induced
      by the plasmon coupling of gold nanoparticle dimers.
AB  - Gold nanoparticle dimers assembled on the surface of CdS QD thin films served as
      nano-antennas to mediate the distance-dependent plasmon enhanced
      electrochemiluminescence of QDs.

PMID- 27872917
TI  - Oxygen vacancy induced Bi2WO6 for the realization of photocatalytic CO2 reduction
      over the full solar spectrum: from the UV to the NIR region.
AB  - Photocatalytic CO2 reduction over the UV-Vis-NIR broad spectrum was realized for
      the first time. The presence of surface oxygen vacancy defects on Bi2WO6 resulted
      in significant photocatalytic enhancement over the pristine counterpart under UV
      and visible light irradiation. Meanwhile, the photocatalytic responsiveness of
      Bi2WO6-OV was successfully extended to the NIR region.

PMID- 27872919
TI  - Core expansion of bis-calix[4]arene-supported clusters.
AB  - Calix[4]arenes are excellent ligand supports for the synthesis of polymetallic
      clusters of transition and lanthanide metal ions, as well as 3d-4f ion mixtures.
      Bis-calix[4]arene, a recent addition to the calixarene family, forms structurally
      related cages that mirror the metal ion binding preferences of calix[4]arene.
      Here we show that stoichiometric control causes remarkable expansion in the cores
      of two known bis-calix[4]arene-supported clusters, with concomitant changes to
      the magnetic properties observed.

PMID- 27872921
TI  - Synthesis of stilbene derivatives via visible-light-induced cross-coupling of
      aryl diazonium salts with nitroalkenes using -NO2 as a leaving group.
AB  - The straightforward visible-light-induced synthesis of stilbene compounds via the
      cross-coupling of nitroalkenes and diazonium tetrafluoroborates under transition
      metal-free conditions is described. The protocol uses green LEDs as light sources
      and eosin Y as an organophotoredox catalyst. Broad substrate scope and exclusive
      selectivity for the (E)-configuration of stilbenes are observed. This protocol
      proceeds via a radical pathway, with nitroalkenes serving as the radical
      acceptor, and the nitro group is cleaved during the process.

PMID- 27872920
TI  - Ultrafast chiral separations for high throughput enantiopurity analysis.
AB  - Recent developments in fast chromatographic enantioseparations now make high
      throughput analysis of enantiopurity on the order of a few seconds achievable.
      Nevertheless, routine chromatographic determinations of enantiopurity to support
      stereochemical investigations in pharmaceutical research and development,
      synthetic chemistry and bioanalysis are still typically performed on the 5-20 min
      timescale, with many practitioners believing that sub-minute enantioseparations
      are not representative of the molecules encountered in day to day research. In
      this study we develop ultrafast chromatographic enantioseparations for a variety
      of pharmaceutically-related drugs and intermediates, showing that sub-minute
      resolutions are now possible in the vast majority of cases by both supercritical
      fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC).
      Examples are provided illustrating how such methods can be routinely developed
      and used for ultrafast high throughput analysis to support enantioselective
      synthesis investigations.

PMID- 27872922
TI  - Birnessite-type MnO2 nanosheet arrays with interwoven arrangements on vapor grown
      carbon fibers as hybrid nanocomposites for pseudocapacitors.
AB  - Manganese dioxide nanosheet arrays with interconnected arrangements are easily
      synthesized on vapor grown carbon fibers (MnO2 NSAs@VCFs) by a simple wet
      chemical method at low temperature. The conductive nature of the VCFs serves as a
      scaffold and easily reduces potassium permanganate species for the formation of
      hierarchical MnO2 NSAs@VCFs. When utilized as an electroactive material for
      pseudocapacitors, the sophisticated configuration of the nanocomposite provides
      an effective electrochemical activity and an electron pathway for higher
      electrochemical performance in 1 M Na2SO4 aqueous solution. The hierarchical MnO2
      NSAs@VCFs exhibit a maximum specific capacitance of 115.3 F g-1 at a current
      density of 0.5 A g-1 with an excellent cycling stability of 85.6% after 2000
      cycles at a current density of 5 A g-1. Such facile and cost-effective
      fabrication of a metal oxide nanocomposite with improved electrochemical
      performance allows it to be considered as a promising electroactive material for
      energy storage devices.

PMID- 27872923
TI  - The stepwise generation of multimetallic complexes based on a vinylbipyridine
      linkage and their photophysical properties.
AB  - The versatile rhenium complex [ReCl(CO)3(bpyC[triple bond, length as m-dash]CH)]
      (HC[triple bond, length as m-dash]Cbpy = 5-ethynyl-2,2'-bipyridine) is used to
      generate a series of bimetallic complexes through the hydrometallation of
      [MHCl(CO)(BTD)(PPh3)2] (M = Ru, Os; BTD = 2,1,3-benzothiadiazole). The ruthenium
      complex [Ru{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}Cl(BTD)(CO)(PPh3)2]
      was characterised structurally. Ligand exchange reactions with bifunctional
      linkers bearing oxygen and sulfur donors provide access to tetra- and
      pentametallic complexes such as [{M{CH[double bond, length as m-dash]CH
      bpyReCl(CO)3}(CO)(PPh3)2}2(S2CNC4H8NCS2)] and Fe[C5H4CO2M{CH[double bond, length
      as m-dash]CH-bpyReCl(CO)3}(CO)(PPh3)2]2. The effect of the group 8 metal on the
      photophysical properties of the rhenium centre was investigated using the
      complexes [Ru{CH[double bond, length as m-dash]CH
      bpyReCl(CO)3}Cl(BTD)(CO)(PPh3)2] and [M{CH[double bond, length as m-dash]CH
      bpyReCl(CO)3}{S2P(OEt)2}(CO)(PPh3)2] (M = Ru, Os). This revealed the quenching of
      the rhenium-based emission in favour of weak radiative processes based on the Ru
      and Os centres. The potential for exploiting this effect is illustrated by the
      reaction of [Ru{CH[double bond, length as m-dash]CH
      bpyReCl(CO)3}Cl(CO)(BTD)(PPh3)2] with carbon monoxide, which results in a 5-fold
      fluorescence enhancement in the dicarbonyl product, [Ru{CH[double bond, length as
      m-dash]CH-bpyReCl(CO)3}Cl(CO)2(PPh3)2], as the quenching effect is disrupted.

PMID- 27872924
TI  - One dimensional metal dithiolene (M = Ni, Fe, Zn) coordination polymers for the
      hydrogen evolution reaction.
AB  - Immobilization of metal complexes to electrode surfaces has emerged as an
      attractive strategy to combine homogeneous and heterogeneous catalysis. We
      recently reported the immobilization of cobalt dithiolene catalytic units via
      incorporation into extended one and two dimensional (1D and 2D) frameworks. We
      extend here this methodology to the formation of 1D nickel, iron, and zinc
      dithiolene coordination polymers based on benzene-1,2,4,5-tetrathiolate (BTT)
      frameworks and investigate their catalytic H2-evolving activities under fully
      aqueous conditions. The nickel dithiolene coordination polymer is an active
      electrocatalyst for the hydrogen evolution reaction (HER). An overpotential of
      470 mV was required to reach a current density of 10 mA cm-2 at pH 1.3, making
      this system one of the best performing heterogenized molecular catalysts for HER.
      This overpotential is 90 mV lower than that of the cobalt analogue, suggesting
      that the nickel coordination polymer is a more efficient H2-evolving catalyst.
      Additionally, no decrease in activity is observed for the nickel polymer during
      the first hour of electrolysis, indicating that it is stable under prolonged
      electrolysis.

PMID- 27872925
TI  - New dinuclear ruthenium arene complexes containing thiosemicarbazone ligands:
      synthesis, structure and cytotoxic studies.
AB  - A series of mononuclear ruthenium arene complexes with thiosemicarbazone (TSC)
      ligands (A-type, 1-8) and their corresponding di-nuclear analogues (B-type, 9-16)
      were synthesized and characterized by NMR, elemental analysis and HR-ESI-mass
      spectrometry. The molecular structures of 1, 2, 6, 9-11 and 13-16 were determined
      using single-crystal X-ray diffraction analysis. The Gibbs free energy of the two
      examples of the two types of complexes (1 and 9) and the bonding order in their
      single-crystals were studied using density functional theory (DFT) calculations.
      The compounds were further evaluated for their in vitro antiproliferative
      activities against CNE-2 human nasopharyngeal carcinoma, KB human oral epithelial
      carcinoma, SGC-7901 human gastric carcinoma, HepG2 human liver carcinoma, HeLa
      human cervical carcinoma and HEK-293T noncancerous cell lines. Furthermore, the
      interactions between the compounds and DNA were studied by electrophoretic
      mobility spectrometry studies.

PMID- 27872926
TI  - Copper-catalyzed synthesis of 2-aminobenzothiazoles from 2-iodophenyl
      isocyanides, potassium sulfide and amines.
AB  - A simple and practically useful synthetic method for the synthesis of a variety
      of 2-aminobenzothiazoles was developed. This methodology could construct one C-N
      bond and two C-S bonds in a step reaction and provide the desired products in
      good to perfect yields.

PMID- 27872927
TI  - Highly efficient extraction of actinides with pillar[5]arene-derived
      diglycolamides in ionic liquids via a unique mechanism involving competitive host
      guest interactions.
AB  - Actinide partitioning is considered as one of the most challenging issues in
      nuclear waste remediation. Herein, we unravel a novel extraction mode pertinent
      to the competitive host-guest interactions for highly efficient actinide
      extraction. The host-guest recognition event involves binding of a room
      temperature ionic liquid (RTIL), 1-n-octyl-3 methylimidazolium
      bis(trifluoromethane)sulfonamide (C8mimNTf2), as both the guest and the solvent
      by the hosts pillar[5]arene-based diglycolamides (P5DGAs) and the subsequent
      displacement of the guest by a metal ion. This two-step process suggests a unique
      competitive ion-mediated displacement mechanism for the metal ion partitioning in
      the extraction process. The supramolecular extraction system is evaluated for its
      extraction abilities towards actinide ions such as UO22+, PuO22+, Pu4+, Am3+, and
      fission product elements such as Eu3+, Sr2+, Cs+. The results demonstrate the
      exceedingly high distribution ratios and favorable separation of Am3+ and Pu4+ in
      nitric acid media. All the three P5DGAs form 1 : 1 complexes with Am3+. Time
      resolved laser fluorescence spectroscopic (TRLFS) studies reveal a strong
      complexation involving no inner-sphere water molecules in the Eu3+-P5DGA
      complexes when C8mimNTf2 is used as the diluent. With high efficiency in the
      extraction of actinides and a quantitative back extraction outcome, the RTIL
      based solvent systems containing pillar[5]arene-DGA ligands developed in this
      work hold potential as promising candidates for nuclear waste remediation in a
      more sustainable fashion.

PMID- 27872928
TI  - Drop morphologies on flexible fibers: influence of elastocapillary effects.
AB  - Various materials are made of long thin fibers that are randomly oriented to form
      a complex network in which drops of wetting liquid tend to accumulate at the
      nodes. The capillary force exerted by the liquid can bend flexible fibers, which
      in turn influences the morphology adopted by the liquid. In this paper, we
      investigate through a model situation the role of the fiber flexibility on the
      shape of a small volume of liquid on a pair of crossed flexible fibers. We
      characterize the liquid morphologies as we vary the volume of liquid, the angle
      between the fibers, and the length of the fibers. The drop morphologies
      previously reported for rigid crossed fibers, i.e., a drop, a column and a mixed
      morphology, are also observed on flexible crossed fibers with modified domains of
      existence. In addition, at small tilt angles between the fibers, a new behavior
      is observed: the fibers bend and collapse. Depending on the volume of liquid, a
      thin column with or without a drop is reported on the collapsed fibers. Our study
      suggests that the fiber flexibility adds a rich variety of behaviors that may be
      important for some applications.

PMID- 27872930
TI  - The inhibition effect of starch nanoparticles on tyrosinase activity and its
      mechanism.
AB  - The objective of the current research was to investigate the effects of starch
      nanoparticles (SNPs) prepared from waxy maize, potato, normal corn, and tapioca
      starches on the activity of tyrosinase. As a main polyphenol oxidase, tyrosinase
      not only induces fruit and vegetable browning but also causes skin diseases by
      overproducing melanin. Herein, for the first time, we evaluated the inhibitory
      kinetics of SNPs on tyrosinase. It turned out that SNPs inhibited tyrosinase
      activity reversibly. The IC50 values of hollow nanoparticles, amylopectin
      nanoparticles, corn starch nanoparticles, and tapioca starch nanoparticles were
      0.308, 0.669, 1.490, and 4.774 MUM, respectively. Assay of fluorescence spectra
      demonstrated that SNPs quenched the tyrosinase intrinsic fluorescence. Moreover,
      binding constant and binding sites found that SNPs were bound to tyrosinase
      through van der Waals forces, hydrogen bonds, as well as electrostatic
      interactions. Analysis of circular dichroism indicated that the incorporation of
      SNPs into tyrosinase prompted conformational alteration of the enzyme.
      Furthermore, inhibition of browning by SNPs loading with l-dopa compound
      indicated that not only the tyrosinase activity was inhibited, but also SNPs
      decreased free dopa content by adsorption. This research on SNPs as potential
      inhibitors could give rise to advancement in the realm of anti-tyrosinase and
      have versatile applications in medicine, food, cosmetics, materials and drugs.

PMID- 27872929
TI  - Magnetic iron oxide modified pyropheophorbide-a fluorescence nanoparticles as
      photosensitizers for photodynamic therapy against ovarian cancer (SKOV-3) cells.
AB  - Magnetic iron oxide modified pyropheophorbide-a fluorescence nanoparticles,
      Fe3O4@SiO2@APTES@PPa (FSAP), were designed as magnetically targeted photodynamic
      antineoplastic agents and prepared through continuous covalent chemical
      modification on the surface of Fe3O4 nanoparticles. The properties of the
      intermediates and the final product were comprehensively characterized by
      transmission electron microscopy, powder X-ray diffraction analysis, Fourier
      transform infrared spectroscopy, vibrating sample magnetometry, zeta potential
      measurement, ultraviolet-visible absorption spectroscopy, fluorescence emission
      spectroscopy, and thermogravimetric analysis. In this work, we demonstrated the
      in vitro photodynamic therapy (PDT) of FSAP against ovarian cancer (SKOV-3)
      cells, which indicated that FSAP could be taken up successfully and showed low
      dark toxicity without irradiation, but remarkable phototoxicity after
      irradiation. Meanwhile, FSAP had showed good biocompatibility and low dark
      toxicity against normal cells in the biological experiments on mouse normal
      fibroblast cell lines (L929 cells). In addition, in the photochemical process of
      FSAP mediated photodynamic therapy, the Type-II photo-oxygenation process
      (generated singlet oxygen) played an important role in the induction of cell
      damage.

PMID- 27872931
TI  - A diarylethene-derived probe for colorimetric detection of CN- and highly
      selective fluorescent recognition of I.
AB  - A new photochromic diarylethene derivative with 2-hydrazinobenzothiazole was
      synthesized, and its multi-controllable switch behavior was investigated in
      detail when triggered by light and anions. When triggered by CN-, the absorption
      spectra of the diarylethene showed a new band at 474 nm with an obvious color
      change from colorless to bright yellow. Upon addition of I-, the diarylethene
      compound displayed a new absorption band at 297 nm and the original absorption at
      370 nm also increased, and the fluorescence intensity exhibited obvious
      fluorescence quenching with fluorescence color change from a light royal blue to
      dark. The results indicated that the diarylethene derivative exhibited naked-eye
      detection of CN- and the fluorescent recognition of I-.

PMID- 27872932
TI  - Phytochemical profiles of marine phytoplanktons: an evaluation of their in vitro
      antioxidant and anti-proliferative activities.
AB  - Marine microorganisms such as phytoplanktons are a rich resource of bioactive
      components with antioxidant and anti-proliferative activities that can act as
      novel functional food ingredients. In this study, the pigment profiles, total
      mycosporine-like amino acids (MAAs) and total phenolic contents (TPCs) in solvent
      extracts including 90% acetone and methanol from five marine phytoplanktons
      including Nitzschia closterium (Bacillariophyta), Isochrysis zhangjiangensis
      (Haptophyta), Platymonas subcordiformis (Chlorophyta), Porphyridium cruentum
      (Rhodophyta) and Synechocystis pevalekii (Cyanobacteria) were analyzed. Each
      phytoplankton from different phyla had its unique compositions of carotenoids and
      chlorophylls. The 90% acetone extract from I. zhangjiangensis had the highest MAA
      content (508.30 MUg per g DW) while the methanol extract from N. closterium had
      the highest level of TPCs (6.15 mg GAE per g DW) among all the phytoplanktons
      investigated. The amounts of total carotenoids in all the 90% acetone extracts
      from the five phytoplanktons as well as total MAAs in those from within the four
      microalgae except S. pevalekii were found to be strongly correlated with their
      antioxidant activities evaluated by the DPPH, TEAC and FRAP assays. Only the
      level of total carotenoids in the phytoplanktons was correlated with their anti
      proliferative activities assessed by the MTT assays using MCF-7 cells. Therefore,
      individual carotenoid pigments seemed to be mainly responsible for the
      antioxidant and anti-proliferative (or anticancer) activities found in the
      solvent extracts of the five phytoplanktons. Hence these phytoplanktons have the
      potential as novel sources of natural food antioxidants and anticancer agents to
      be used as active ingredients in functional food products.

PMID- 27872933
TI  - Assembly of NHC-stabilized 2-hydrophosphasilenes from Si(iv) precursors: a Lewis
      acid-base complex.
AB  - NHC-stabilized 2-hydrophosphasilenes are obtained from 1,2-dihydro-2
      chlorophosphasilanes as Si(iv) precursors by a NHC-assisted 1,2-elimination of
      HCl. The NHC-exchange of these compounds is demonstrated as a proof of donor
      acceptor bonding between NHC and the silicon centre of the "Si[double bond,
      length as m-dash]P" moiety. We have also explored the possibility of similar
      exchanges in NHC-stabilized Si2 and P2 compounds. Theoretical DFT calculations
      were performed to address the nature of Si-P bonding in the NHC-stabilized 2
      hydrophosphasilenes.

PMID- 27872934
TI  - Indirect synthesis of a pair of formal methane activation products at a
      phosphane/borane frustrated Lewis pair.
AB  - The regioisomeric formal Mes2PCH2CH2B(C6F5)2 FLP methane splitting products
      Mes2P(H)CH2CH2B(CH3)(C6F5)2 and Mes2P(CH3)CH2CH2B(H)(C6F5)2 were produced by
      indirect stepwise reactions. They were stable at 60  degrees C and were both
      characterized by X-ray diffraction. A DFT analysis revealed that their formation
      from the FLP and CH4 would be endergonic by +6.9 and +3.6 kcal mol-1,
      respectively, and it indicated that methane elimination from the zwitterionic
      products is kinetically hindered by barriers of 54.0 and 72.3 kcal mol-1,
      respectively.

PMID- 27872935
TI  - The social transformation of Singapore medicine through 55 years of the SMJ.
AB  - The Singapore Medical Journal (SMJ) has in the past 55 years reflected the
      phenomenal socioeconomic progress of Singapore. Publications in the pre
      independent years were mainly on diseases like cholera, diphtheria, leprosy,
      tetanus and worm infestation. In the new millennium, the research papers included
      molecular genetics, health economics, obesity, Internet medicine, cancer,
      cosmetic surgery and palliative medicine. The annual SMA Lecture published in the
      SMJ provides an ethical compass for doctors to remind them of primum non nocere.

PMID- 27872936
TI  - Clinics in diagnostic imaging (171). Caecal volvulus with underlying intestinal
      malrotation.
AB  - A 46-year-old Chinese woman with a history of cholecystectomy and appendicectomy
      presented to the emergency department with symptoms of intestinal obstruction.
      Physical examination revealed central abdominal tenderness but no clinical
      features of peritonism. Plain radiography of the abdomen revealed a grossly
      distended large bowel loop with the long axis extending from the right lower
      abdomen toward the epigastrium, and an intraluminal air-fluid level. These
      findings were suspicious for an acute caecal volvulus, which was confirmed on
      subsequent contrast-enhanced computed tomography (CT) of the abdomen and pelvis.
      CT demonstrated an abnormal positional relationship between the superior
      mesenteric vein and artery, indicative of an underlying intestinal malrotation.
      This case highlights the utility of preoperative imaging in establishing the
      diagnosis of an uncommon cause of bowel obstruction. It also shows the importance
      of recognising the characteristic imaging features early, so as to ensure
      appropriate and expedient management, thus reducing patient morbidity arising
      from complications.

PMID- 27872939
TI  - Medicine and diplomacy.

PMID- 27872938
TI  - Evaluation of solid breast lesions with power Doppler: value of penetrating
      vessels as a predictor of malignancy.
AB  - INTRODUCTION: This study aimed to evaluate the vascular pattern of solid breast
      lesions using power Doppler ultrasonography (PDUS) and assess whether the
      presence of intratumoural penetrating vessels can predict breast cancer
      malignancy. METHODS: Greyscale ultrasonography (US) and PDUS were prospectively
      performed on 91 women in Malaysia with histopathologically proven breast lesions.
      The diagnostic accuracy of greyscale US, PDUS, and both greyscale US and PDUS was
      calculated and compared. RESULTS: The 91 women had 102 breast lesions (55 benign,
      47 malignant). Of the 47 malignant lesions, 36 demonstrated intratumoural
      penetrating vessels. The sensitivity, specificity, positive predictive value
      (PPV) and negative predictive value (NPV) of greyscale US findings in diagnosing
      malignancy were 100.0%, 71.4%, 74.1% and 100.0%, respectively. The presence of
      calcification in the breast lesion and the margin, shape and posterior acoustic
      features of the lesion were significant parameters in predicting malignancy (p <
      0.01). The sensitivity, specificity, PPV and NPV of the presence of intratumoural
      penetrating vessels in predicting malignancy were 76.5%, 80.0%, 76.5% and 80.0%,
      respectively. When both greyscale US and PDUS were used, there was a significant
      correlation in predicting malignancy (p < 0.05). The specificity and PPV values
      of the combined greyscale US and PDUS method (89.0% and 85.7%, respectively) were
      higher than those of greyscale US or PDUS alone. CONCLUSION: Flow patterns
      revealed by PDUS can be useful for differentiating benign and malignant breast
      lesions. The visualisation of penetrating vessels in solid breast lesions can be
      used to complement greyscale US findings in predicting malignancy.

PMID- 27872937
TI  - Major depression in primary care: making the diagnosis.
AB  - Major depression is a common condition seen in the primary care setting, often
      presenting with somatic symptoms. It is potentially a chronic illness with
      considerable morbidity, and a high rate of relapse and recurrence. Major
      depression has a bidirectional relationship with chronic diseases, and a strong
      association with increased age and coexisting mental illnesses (e.g. anxiety
      disorders). Screening can be performed using clinical tools for major depression,
      such as the Patient Health Questionaire-2, Patient Health Questionaire-9 and Beck
      Depression Inventory, so that timely treatment can be initiated. An accurate
      diagnosis of major depression and its severity is essential for prompt treatment
      to reduce morbidity and mortality. This is the first of a series of articles that
      illustrates the approach to the management of major depression in primary care.
      Our next articles will cover suicide risk assessment in a depressed patient and
      outline the basic principles of management and treatment modalities.

PMID- 27872940
TI  - Cholestyramine as monotherapy for Graves' hyperthyroidism.

PMID- 27872941
TI  - [Supraglottoplasty for pediatric laryngomalacia : Results from 71 cases].
AB  - Laryngomalacia is the most common cause of stridor in infants. The stridor is
      caused by an inward collapse of supraglottic structures during inspiration
      resulting in an inspiratory stridor. The exact etiology still remains unclear.
      The surgical procedure of choice for laryngomalacia is supraglottoplasty. From
      2009 to 2016 a total of 71 children were treated by supraglottoplasty in the
      department for pediatric otorhinolaryngology of the Stuttgart Hospital. The
      indications for supraglottoplasty were laryngomalacia with severe inspiratory
      stridor, oxygen desaturation, suprasternal or chest retraction, feeding
      difficulties and/or failure to thrive. The overall success rate was 86 % but
      there was a clear difference between children with isolated laryngomalacia and
      the group with associated comorbidities. The success rate for patients with
      isolated laryngomalacia was 98 % and for patients with associated comorbidities
      57 %. Supraglottoplasty is therefore an effective and safe treatment for
      symptomatic laryngomalacia and a reduction in the success rate showed a clear
      correlation with the presence of congenital comorbidities.

PMID- 27872942
TI  - Graphical genotyping as a method to map Ny (o,n)sto and Gpa5 using a reference
      panel of tetraploid potato cultivars.
AB  - KEY MESSAGE: The method of graphical genotyping is applied to a panel of
      tetraploid potato cultivars to visualize haplotype sharing. The method allowed to
      map genes involved in virus and nematode resistance. The physical coordinates of
      the amount of linkage drag surrounding these genes are easily interpretable.
      Graphical genotyping is a visually attractive and easily interpretable method to
      represent genetic marker data. In this paper, the method is extended from
      diploids to a panel of tetraploid potato cultivars. Application of filters to
      select a subset of SNPs allows one to visualize haplotype sharing between
      individuals that also share a specific locus. The method is illustrated with
      cultivars resistant to Potato virus Y (PVY), while simultaneously selecting for
      the absence of the SNPs in susceptible clones. SNP data will then merge into an
      image which displays the coordinates of a distal genomic region on the northern
      arm of chromosome 11 where a specific haplotype is introgressed from the wild
      potato species S. stoloniferum (CPC 2093) carrying a gene (Ny (o,n)sto )
      conferring resistance to two PVY strains, PVYO and PVYNTN. Graphical genotyping
      was also successful in showing the haplotypes on chromosome 12 carrying Ry-f sto
      , another resistance gene derived from S. stoloniferum conferring broad-spectrum
      resistance to PVY, as well as chromosome 5 haplotypes from S. vernei, with the
      Gpa5 locus involved in resistance against Globodera pallida cyst nematodes. The
      image also shows shortening of linkage drag by meiotic recombination of the
      introgression segment in more recent breeding material. Identity-by-descent was
      found to be a requirement for using graphical genotyping, which is proposed as a
      non-statistical alternative method for gene discovery, as compared with genome
      wide association studies. The potential and limitations of the method are
      discussed.

PMID- 27872944
TI  - [Multiple eccrine hidrocystomas on the lower forehead and nose of a 60-year-old
      man].
AB  - Multiple eccrine hidrocystomas are benign cystic skin lesions which originate
      from the sweat gland ducts and typically affect women's midfacial area. Sweating
      may lead to an increase in size of the translucent papules. In some cases
      hidrocystomas are associated with other diseases such as Parkinson's disease.
      Treatment options include laser, topical and systemic anticholinergic drugs
      (glycopyrrolate, clonidine, atropine, and oxybutynin), whereby therapeutic
      success is limited in most cases.

PMID- 27872943
TI  - [Adverse drug reactions in elderly people : First data from the Leipzig Research
      Center for Civilization Diseases (LIFE)].
AB  - BACKGROUND: Few data exist on adverse drug reactions (ADR) in elderly people. In
      this group, pharmacotherapy represents a challenge with regard to comorbidities,
      drug interactions and compliance. OBJECTIVE: The aim of this article is to
      highlight the characteristics of ADR in elderly patients. METHODS: In addition to
      a literature review we present the first data from the Leipzig Research Center
      for Civilization Diseases (LIFE). Between 2011 and 2015 a total of 9537 subjects
      aged 40-79 years were randomly included in this population-based, age and sex
      standardized investigation in the inhabitants of Leipzig, Germany and special
      emphasis was placed on allergies including questions with regard to ADR. RESULTS:
      Of the 9537 subjects, data on allergies were available from 8979 subjects. Female
      gender, comorbidities and the use of multiple drugs were significantly associated
      with an increased risk of ADR. Women also reported ADR significantly more
      frequently than men. Of the subjects 22% reported suffering from some form of ADR
      as a result of medications, while in 2.3% this reaction had occurred within the
      previous 12 months. Less than 15% of LIFE patients with ADR were in possession of
      a document giving details of the ADR. DISCUSSION: The occurrence of ADR
      significantly contributes to morbidity in elderly patients. For prevention of ADR
      knowledge of patient-related factors, underlying diseases, drug characteristics
      and drug interactions are necessary.

PMID- 27872945
TI  - Ascaris lumbricoides egg die-off in an experimental excreta storage system and
      public health implication in Vietnam.
AB  - OBJECTIVES: We studied the influence of different additive materials (lime, and
      rice husk) and aeration conditions on Ascaris lumbricoides egg die-off in 24
      vaults of an experimental excreta storage unit. METHODS: Excreta samples were
      collected once every two weeks over a 181-day period. Temperature, pH, and
      moisture content were recorded. A. lumbricoides eggs were quantitatively analyzed
      by the Romanenko method, which identified and counted live and dead eggs.
      RESULTS: From the first sampling (0 storage day) to the final sampling (181
      storage days) the average percentage of viable A. lumbricoides eggs decreased
      gradually from 76.72 +/- 11.23% (mean +/- SD) to 8.26 +/- 5.20%. The storage time
      and the high pH value significantly increased the die-off of helminth eggs. Over
      181 storage days, all vaults option effectively reduced A. lumbricoides eggs die
      off. CONCLUSIONS: The best vault option, with aeration and 10% lime per total
      weight, met the WHO standard for excreta treatment on the 111th storage day.

PMID- 27872948
TI  - Glucose concentrations of less than 3.0 mmol/l (54 mg/dl) should be reported in
      clinical trials: a joint position statement of the American Diabetes Association
      and the European Association for the Study of Diabetes.

PMID- 27872946
TI  - Implementation of image-guided intensity-modulated accelerated partial breast
      irradiation : Three-year results of a phase II clinical study.
AB  - PURPOSE: To report 3-year results of accelerated partial breast irradiation
      (APBI) using image-guided intensity-modulated radiotherapy (IG-IMRT) following
      breast conserving surgery (BCS) for low-risk early invasive breast cancer.
      PATIENTS AND METHODS: Between July 2011 and March 2014, 60 patients with low-risk
      early invasive breast cancer underwent BCS and were enrolled in this phase II
      prospective study. The total dose was 36.9 Gy (9 fractions of 4.1 Gy, two
      fractions/day). Patient setup errors were detected in LAT, LONG and VERT
      directions. Local tumour control, survival results, early and late side effects
      and cosmetic outcome were assessed. RESULTS: At a median follow-up of 39 months,
      all patients were alive and neither locoregional nor distant failure occurred.
      One contralateral breast cancer and two new primary malignancies outside the
      breast were observed. No grade (G) 3-4 acute toxicity was detected. G1 and G2
      erythema occurred in 21 (35%) and 2 (3.3%) patients, respectively; while G1
      oedema was observed in 23 (38.8%) cases. G1 and G2 pain was reported by 6 (10%)
      and 2 (3.3%) patients, respectively. Among the late radiation side effects, G1
      pigmentation or telangiectasia, G1 fibrosis and G1 asymptomatic fat necrosis
      occurred in 10 (16.7%), 7 (11.7%) and 3 (5%) patients, respectively. No >= G2
      late toxicity was detected. Cosmetic outcome was excellent in 43 (71.7%) and good
      in 17 (28.3%) patients. CONCLUSION: IG-IMRT is a reproducible and feasible
      technique for delivery of external beam APBI following BCS for treatment of low
      risk, early-stage invasive breast carcinoma. In order to avoid toxicity, image
      guidance performed before each radiation fraction is necessary to minimize the
      PTV. Three-year results are promising, early and late radiation side-effects are
      minimal, and cosmetic results are excellent to good.

PMID- 27872947
TI  - Design and characterisation of synthetic operons for biohydrogen technology.
AB  - Biohydrogen is produced by a number of microbial systems and the commonly used
      host bacterium Escherichia coli naturally produces hydrogen under fermentation
      conditions. One approach to engineering additional hydrogen production pathways
      is to introduce non-native hydrogenases into E. coli. An attractive candidate is
      the soluble [NiFe]-hydrogenase from Ralstonia eutropha, which has been shown to
      link NADH/NAD+ biochemistry directly to hydrogen metabolism, an activity that E.
      coli does not perform. In this work, three synthetic operons were designed that
      code for the soluble hydrogenase and two different enzyme maturase systems.
      Interestingly, using this system, the recombinant soluble hydrogenase was found
      to be assembled by the native E. coli [NiFe]-hydrogenase assembly machinery, and,
      vice versa, the synthetic maturase operons were able to complement E. coli
      mutants defective in hydrogenase biosynthesis. The heterologously expressed
      soluble hydrogenase was found to be active and was shown to produce biohydrogen
      in vivo.

PMID- 27872949
TI  - Symbiont Diversity of Aphis (Toxoptera) citricidus (Hemiptera: Aphididae) as
      Influenced by Host Plants.
AB  - Aphids are well known for their association with endosymbiont bacteria. Almost
      all aphids harbor Buchnera aphidicola as an obligate symbiont and several other
      bacteria as facultative symbionts. Associations of facultative symbionts and
      aphids are quite variable in terms of diversity and prevalence across aphid
      species. Facultative symbionts can have a major impact on aphid bioecological
      traits. A number of factors shape the outcome of the facultative symbiont-aphid
      association, including aphid clone, bacterial genotype, geography, and host plant
      association. The effects of host plant on aphid-facultative symbiont associations
      are the least understood. We performed deep sequencing of the bacterial community
      associated with field populations of the oligophagous aphid Aphis (Toxoptera)
      citricidus collected from different host plants. We demonstrate that (i) A.
      citricidus has low symbiont diversity, (ii) symbiont diversity is affected by
      host plant, and (iii) host plants affect the relative abundance of the obligate
      symbiont Buchnera and an unknown genus of Enterobacteriaceae.

PMID- 27872950
TI  - A new speech enhancement device for critically ill patients with communication
      problems: a prospective feasibility study.

PMID- 27872952
TI  - Molecular Phylogenetics and the Perennial Problem of Homology.
AB  - The concept of homology has a long history, during much of which the issue has
      been how to reconcile similarity and common descent when these are not
      coextensive. Although thinking molecular phylogeneticists have learned not to say
      "percent homology," the problems are deeper than that and unresolved.

PMID- 27872951
TI  - Immunogenicity and efficacy of a rationally designed vaccine against vascular
      endothelial growth factor in mouse solid tumor models.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in the
      progression of various cancers. The VEGF-specific antibody bevacizumab combined
      with chemotherapy was shown to significantly improve progression-free survival in
      certain cancers. However, repeated administration is necessary for effective
      suppression of VEGF, thereby making the therapy expensive and cumbersome. Thus,
      it is urgent to develop alternative reagents such as VEGF vaccines. Here we
      report that DTT-VEGF, a VEGF-based antigen consisting of the receptor-binding
      domain of VEGF and diphtheria toxin T domain (DTT), not only stimulated
      neutralizing antibody response, but also induced type 1 immune response as well
      as anti-tumor cytotoxic T lymphocytes in mice when administered with aluminum
      hydroxide adjuvant. The antibodies triggered by DTT-VEGF immunization inhibited
      the binding of VEGF to VEGF receptor and downregulated the serum VEGF levels in
      tumor-bearing mice. VEGF-specific IgG2a and IgG2b antibodies as well as type 1
      cytokines were stimulated by DTT-VEGF vaccination. The splenocytes from DTT-VEGF
      immunized mice showed cytotoxic activity against B16-F10 cells expressing VEGF.
      Extensive necrosis with severe hemorrhage and enhanced CD8+ T cell infiltration
      were observed in tumors from DTT-VEGF-immunized mice. The percentages of CD31+
      vascular areas in the tumor sections from DTT-VEGF-immunized mice were
      significantly lower than those of control mice. DTT-VEGF significantly inhibited
      tumor growth in preventive and therapeutic vaccination settings in mouse models.
      Our data suggest that DTT is an effective antigen carrier to break immune self
      tolerance and our vaccine design has potential to be used for human cancer
      therapy.

PMID- 27872953
TI  - A phase I study of afatinib combined with paclitaxel and bevacizumab in patients
      with advanced solid tumors.
AB  - PURPOSE: The combination of afatinib, an irreversible ErbB family blocker, with
      paclitaxel and bevacizumab was assessed in patients with advanced solid tumors.
      METHODS: This phase I study used a 3 + 3 design to determine the maximum
      tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab.
      Safety, pharmacokinetics, and anti-tumor activity were also assessed. The
      starting dose was oral afatinib 40 mg once daily plus intravenous paclitaxel
      (fixed dose 80 mg/m2, Days 1, 8, and 15 of a 4-week cycle) and intravenous
      bevacizumab 5 mg/kg every 2 weeks. RESULTS: Twenty-nine patients were enroled.
      The afatinib dose was de-escalated to 30 mg and then 20 mg after 2/6 and 2/5
      evaluable patients developed dose-limiting toxicities at 40 and 30 mg,
      respectively, when combined with paclitaxel and bevacizumab 5 mg/kg. The
      bevacizumab dose was subsequently escalated to 10 mg/kg, and MTD was defined as
      afatinib 20 mg plus paclitaxel 80 mg/m2 and bevacizumab 10 mg/kg. Frequent (any
      grade) treatment-related adverse events (AEs) included diarrhea (83%), rash/acne
      (83%), fatigue (79%), mucosal inflammation (59%), and nausea (59%). Based on
      overall safety, bevacizumab was amended to 7.5 mg/kg for the recommended phase II
      dose. Pharmacokinetic analyses suggested no relevant drug-drug interactions.
      Three (10%) confirmed partial responses were observed; 15 (52%) patients had
      stable disease. CONCLUSIONS: The recommended phase II dose schedule was afatinib
      20 mg/day with paclitaxel 80 mg/m2 (Days 1, 8, and 15 every 4 weeks) and
      bevacizumab 7.5 mg/kg every 2 weeks. At this dose schedule, AEs were manageable,
      and anti-tumor activity was observed.

PMID- 27872954
TI  - Osteitis: a retrospective feasibility study comparing single-source dual-energy
      CT to MRI in selected patients with suspected acute gout.
AB  - OBJECTIVE: Dual-energy computed tomography detects tophi in patients with chronic
      gout. However, other information that can be obtained from the same scan is not
      the focus of the current research, e.g., the detection of bone marrow edema (BME)
      using virtual bone marrow imaging (VBMI). The aim of this study was to evaluate
      if BME in patients with acute arthritis can be detected with VBMI using magnetic
      resonance imaging (MRI) as the standard of reference. MATERIALS AND METHODS: This
      retrospective study included 11 patients who underwent both MRI and dual-energy
      computed tomography (mean interval of 40 days). BME in MRI (standard of
      reference) and VBMI was judged independently by two different blinded readers.
      phi-correlation coefficient and Cohen's kappa were performed for statistical
      analysis. Approval was waived by the IRB. RESULTS: Two patients with a final
      diagnosis of RA and one with septic arthritis showed osteitis on MRI and VBMI.
      However, in each case, there were individual bones identified with osteitis on
      MRI but not VBMI. Three additional patients with the final diagnosis of RA were
      identified correctly as negative for BME. There was a good correlation between
      both modalities (phi = 0.8; kappa = 0.8). Inter-rater reliability was excellent
      for both modalities (kappa = 0.9). CONCLUSIONS: We have shown that detecting
      osteitis using VBMI is feasible in patients with inflammatory arthritis. Further
      studies are needed on larger, more-targeted populations to better define the
      indications, accuracy, and added value of this technique.

PMID- 27872955
TI  - Iliopsoas bursal extension of lipohemarthrosis: A novel imaging finding
      associated with hip fracture.
AB  - Lipohemarthrosis is well known to be associated with intra-articular fractures
      throughout the body. Despite the relatively common occurrence of hip fracture and
      the frequency of communication between the hip joint and iliopsoas bursa, to the
      best of our knowledge, a fat-fluid level involving the iliopsoas bursa secondary
      to a hip fracture has not previously been reported. The following is a case
      report of a 48-year-old male who sustained an acute femoral neck fracture and was
      found to have distension of the iliopsoas bursa with a fat-fluid level resulting
      from extra-capsular extension of a lipohemarthrosis. The imaging findings,
      relevant anatomy, and potential importance of this finding for the detection of
      hip fracture are discussed.

PMID- 27872956
TI  - Hip fracture registries: utility, description, and comparison.
AB  - : Hip fractures (HF) are prevalent and involve high morbidity and mortality so
      improving their management is important. HF registries are a good way to improve
      knowledge about this condition and its quality of care, while at the same time
      reducing clinical variability, optimizing efficiency, improving outcomes, and
      reducing costs. INTRODUCTION: Hip fractures (HF) are a prevalent fragility
      fracture secondary to osteoporosis that involves high morbidity and mortality.
      They are low-impact fractures, resulting from a fall from a standing or sitting
      height. Despite numerous Clinical Practice Guidelines that establish uniform
      recommendations for their care, great variability persists regarding clinical and
      healthcare outcomes. Fracture registries can help detect deficits and establish
      measures to improve care. The objective of this work is to analyze the contents
      that a HF registry should have and to compare the characteristics of some
      national HF registries. METHODS: A literature search was conducted on several
      national hip fracture registries, and those that contain relevant information on
      the variables and their outcomes were selected. RESULTS: The selected HF
      registries were compared using the parameters they measure as well as the
      outcomes in the different countries. The variables collected in the majority of
      the databases and those that give useful information are as follows:
      sociodemographic variables (age, sex, place of residence), clinical variables
      (function before and after HF, anesthesia risk as measured by the ASA score, type
      of fracture, type of surgery and anesthesia, and in-hospital and 1-month
      mortality), and healthcare variables (pre-operative and overall stay, presence of
      collaboration with orthogeriatrics or with any clinician in addition to the
      surgeon, secondary prevention of new fractures by assessing the fall risk, and
      need for osteoporosis treatment). CONCLUSION: The recording of HF cases in
      different countries improves knowledge about handling this condition and its
      quality of care, while at the same time reducing clinical variability, optimizing
      efficiency, improving outcomes, and reducing costs. The debate on the variables
      that should be recorded is timely, such as organizing how to collect each
      measurement, and even trying to unify the national and international registries
      or using a current proposal such as the one from the Fragility Fracture Network.

PMID- 27872957
TI  - Utility of 18F-fluoroestradiol (18F-FES) PET/CT imaging as a pharmacodynamic
      marker in patients with refractory estrogen receptor-positive solid tumors
      receiving Z-endoxifen therapy.
AB  - BACKGROUND: Z-endoxifen is the most potent of the metabolites of tamoxifen, and
      has the potential to be more effective than tamoxifen because it bypasses
      potential drug resistance mechanisms attributable to patient variability in the
      expression of the hepatic microsomal enzyme CYP2D6. 18F-FES is a positron
      emission tomography (PET) imaging agent which selectively binds to estrogen
      receptor alpha (ER-alpha) and has been used for non-invasive in vivo assessment
      of ER activity in tumors. This study utilizes 18F-FES PET imaging as a
      pharmacodynamic biomarker in patients with ER+ tumors treated with Z-endoxifen.
      METHODS: Fifteen patients were recruited from a parent therapeutic trial of Z
      endoxifen and underwent imaging with 18F-FES PET at baseline. Eight had positive
      lesions on the baseline scan and underwent follow-up imaging with 18F-FES 1-5
      days post administration of Z-endoxifen. RESULTS: Statistically significant
      changes (p = 0.0078) in standard uptake value (SUV)-Max were observed between the
      baseline and follow-up scans as early as 1 day post drug administration.
      CONCLUSION: F-FES PET imaging could serve as a pharmacodynamic biomarker for
      patients treated with ER-directed therapy.

PMID- 27872959
TI  - Corynebacterium glutamicum for Sustainable Bioproduction: From Metabolic
      Physiology to Systems Metabolic Engineering.
AB  - Since its discovery 60 years ago, Corynebacterium glutamicum has evolved into a
      workhorse for industrial biotechnology. Traditionally well known for its
      remarkable capacity to produce amino acids, this Gram-positive soil bacterium,
      has become a flexible, efficient production platform for various bulk and fine
      chemicals, materials, and biofuels. The central turnstile of all these
      achievements is our excellent understanding of its metabolism and physiology.
      This knowledge base, together with innovative systems metabolic engineering
      concepts, which integrate systems and synthetic biology into strain engineering,
      has upgraded C. glutamicum into one of the most successful industrial
      microorganisms in the world.

PMID- 27872958
TI  - Multisensory integration is independent of perceived simultaneity.
AB  - The importance of multisensory integration for perception and action has long
      been recognised. Integrating information from individual senses increases the
      chance of survival by reducing the variability in the incoming signals, thus
      allowing us to respond more rapidly. Reaction times (RTs) are fastest when the
      components of the multisensory signals are simultaneous. This response
      facilitation is traditionally attributed to multisensory integration. However, it
      is unclear if facilitation of RTs occurs when stimuli are perceived as
      synchronous or are actually physically synchronous. Repeated exposure to
      audiovisual asynchrony can change the delay at which multisensory stimuli are
      perceived as simultaneous, thus changing the delay at which the stimuli are
      integrated-perceptually. Here we set out to determine how such changes in
      multisensory integration for perception affect our ability to respond to
      multisensory events. If stimuli perceived as simultaneous were reacted to most
      rapidly, it would suggest a common system for multisensory integration for
      perception and action. If not, it would suggest separate systems. We measured RTs
      to auditory, visual, and audiovisual stimuli following exposure to audiovisual
      asynchrony. Exposure affected the variability of the unisensory RT distributions;
      in particular, the slowest RTs were either speed up or slowed down (in the
      direction predicted from shifts in perceived simultaneity). Additionally, the
      multisensory facilitation of RTs (beyond statistical summation) only occurred
      when audiovisual onsets were physically synchronous, rather than when they
      appeared simultaneous. We conclude that the perception of synchrony is therefore
      independent of multisensory integration and suggest a division between
      multisensory processes that are fast (automatic and unaffected by temporal
      adaptation) and those that are slow (perceptually driven and adaptable).

PMID- 27872960
TI  - Branched-Chain Amino Acids.
AB  - Branched-chain amino acids (BCAAs), viz., L-isoleucine, L-leucine, and L-valine,
      are essential amino acids that cannot be synthesized in higher organisms and are
      important nutrition for humans as well as livestock. They are also valued as
      synthetic intermediates for pharmaceuticals. Therefore, the demand for BCAAs in
      the feed and pharmaceutical industries is increasing continuously. Traditional
      industrial fermentative production of BCAAs was performed using microorganisms
      isolated by random mutagenesis. A collection of these classical strains was also
      scientifically useful to clarify the details of the BCAA biosynthetic pathways,
      which are tightly regulated by feedback inhibition and transcriptional
      attenuation. Based on this understanding of the metabolism of BCAAs, it is now
      possible for us to pursue strains with higher BCAA productivity using rational
      design and advanced molecular biology techniques. Additionally, systems biology
      approaches using augmented omics information help us to optimize carbon flux
      toward BCAA production. Here, we describe the biosynthetic pathways of BCAAs and
      their regulation and then overview the microorganisms developed for BCAA
      production. Other chemicals, including isobutanol, i.e., a second-generation
      biofuel, can be synthesized by branching the BCAA biosynthetic pathways, which
      are also outlined.

PMID- 27872961
TI  - Boosting Anaplerotic Reactions by Pyruvate Kinase Gene Deletion and
      Phosphoenolpyruvate Carboxylase Desensitization for Glutamic Acid and Lysine
      Production in Corynebacterium glutamicum.
AB  - In the 1980s, Shiio and coworkers demonstrated using random mutagenesis that the
      following three phenotypes were effective for boosting lysine production by
      Corynebacterium glutamicum: (1) low-activity-level citrate synthase (CSL), (2)
      phosphoenolpyruvate carboxylase (PEPC) resistant to feedback inhibition by
      aspartic acid (PEPCR), and (3) pyruvate kinase (PYK) deficiency. Here, we
      reevaluated these phenotypes and their interrelationship in lysine production
      using recombinant DNA techniques.The pyk deletion and PEPCR (D299N in ppc)
      independently showed marginal effects on lysine production, but both phenotypes
      synergistically increased lysine yield, demonstrating the importance of PEPC as
      an anaplerotic enzyme in lysine production. Similar effects were also found for
      glutamic acid production. CSL (S252C in gltA) further increased lysine yield.
      Thus, using molecular techniques, the combination of these three phenotypes was
      reconfirmed to be effective for lysine production. However, a simple CSL mutant
      showed instabilities in growth and lysine yield.Surprisingly, the pyk deletion
      was found to increase biomass production in wild-type C. glutamicum ATCC13032
      under biotin-sufficient conditions. The mutant showed a 37% increase in growth
      (based on OD660) compared with the ATCC13032 strain in a complex medium
      containing 100 g/L glucose. Metabolome analysis revealed the intracellular
      accumulation of excess precursor metabolites. Thus, their conversion into biomass
      was considered to relieve the metabolic distortion in the pyk-deleted mutant.
      Detailed physiological studies of various pyk-deleted mutants also suggested that
      malate:quinone oxidoreductase (MQO) is important to control both the
      intracellular oxaloacetic acid (OAA) level and respiration rate. These findings
      may facilitate the rational use of C. glutamicum in fermentation industries.

PMID- 27872963
TI  - Microbial Production of Amino Acid-Related Compounds.
AB  - Corynebacterium glutamicum is the workhorse of the production of proteinogenic
      amino acids used in food and feed biotechnology. After more than 50 years of safe
      amino acid production, C. glutamicum has recently also been engineered for the
      production of amino acid-derived compounds, which find various applications,
      e.g., as synthons for the chemical industry in several markets including the
      polymer market. The amino acid-derived compounds such as non-proteinogenic omega
      amino acids, alpha,omega-diamines, and cyclic or hydroxylated amino acids have
      similar carbon backbones and functional groups as their amino acid precursors.
      Decarboxylation of amino acids may yield omega-amino acids such as beta-alanine,
      gamma-aminobutyrate, and delta-aminovalerate as well as alpha,omega-diamines such
      as putrescine and cadaverine. Since transamination is the final step in several
      amino acid biosynthesis pathways, 2-keto acids as immediate amino acid precursors
      are also amenable to production using recombinant C. glutamicum strains.
      Approaches for metabolic engineering of C. glutamicum for production of amino
      acid-derived compounds will be described, and where applicable, production from
      alternative carbon sources or use of genome streamline will be referred to. The
      excellent large-scale fermentation experience with C. glutamicum offers the
      possibility that these amino acid-derived speciality products may enter large
      volume markets.

PMID- 27872962
TI  - L-Cysteine Metabolism and Fermentation in Microorganisms.
AB  - L-Cysteine is an important amino acid both biologically and commercially.
      Although most amino acids are industrially produced by microbial fermentation, L
      cysteine has been mainly produced by protein hydrolysis. Due to environmental and
      safety problems, synthetic or biotechnological products have been preferred in
      the market. Here, we reviewed L-cysteine metabolism, including biosynthesis,
      degradation, and transport, and biotechnological production (including both
      enzymatic and fermentation processes) of L-cysteine. The metabolic regulation of
      L-cysteine including novel sulfur metabolic pathways found in microorganisms is
      also discussed. Recent advancement in biochemical studies, genome sequencing,
      structural biology, and metabolome analysis has enabled us to use various
      approaches to achieve direct fermentation of L-cysteine from glucose. For
      example, worldwide companies began to supply L-cysteine and its derivatives
      produced by bacterial fermentation. These companies successfully optimized the
      original metabolism of their private strains. Basically, a combination of three
      factors should be required for improving L-cysteine fermentation: that is, (1)
      enhancing biosynthesis: overexpression of the altered cysE gene encoding feedback
      inhibition-insensitive L-serine O-acetyltransferase (SAT), (2) weakening
      degradation: knockout of the genes encoding L-cysteine desulfhydrases, and (3)
      exploiting export system: overexpression of the gene involved in L-cysteine
      transport. Moreover, we found that "thiosulfate" is much more effective sulfur
      source than commonly used "sulfate" for L-cysteine production in Escherichia
      coli, because thiosulfate is advantageous for saving consumption of NADPH and
      relating energy molecules.

PMID- 27872964
TI  - Toward Sustainable Amino Acid Production.
AB  - Because the global amino acid production industry has been growing steadily and
      is expected to grow even more in the future, efficient production by fermentation
      is of great importance from economic and sustainability viewpoints. Many systems
      biology technologies, such as genome breeding, omics analysis, metabolic flux
      analysis, and metabolic simulation, have been employed for the improvement of
      amino acid-producing strains of bacteria. Synthetic biological approaches have
      recently been applied to strain development. It is also important to use
      sustainable carbon sources, such as glycerol or pyrolytic sugars from cellulosic
      biomass, instead of conventional carbon sources, such as glucose or sucrose,
      which can be used as food. Furthermore, reduction of sub-raw substrates has been
      shown to lead to reduction of environmental burdens and cost. Recently, a new
      fermentation system for glutamate production under acidic pH was developed to
      decrease the amount of one sub-raw material, ammonium, for maintenance of culture
      pH. At the same time, the utilization of fermentation coproducts, such as cells,
      ammonium sulfate, and fermentation broth, is a useful approach to decrease waste.
      In this chapter, further perspectives for future amino acid fermentation from one
      carbon compounds are described.

PMID- 27872965
TI  - Novel Technologies for Optimal Strain Breeding.
AB  - The implementation of a knowledge-based bioeconomy requires the rapid development
      of highly efficient microbial production strains that are able to convert
      renewable carbon sources to value-added products, such as bulk and fine
      chemicals, pharmaceuticals, or proteins at industrial scale. Starting from
      classical strain breeding by random mutagenesis and screening in the 1950s via
      rational design by metabolic engineering initiated in the 1970s, a range of
      powerful new technologies have been developed in the past two decades that can
      revolutionize future strain engineering. In particular, next-generation
      sequencing technologies combined with new methods of genome engineering and high
      throughput screening based on genetically encoded biosensors have allowed for new
      concepts. In this chapter, selected new technologies relevant for breeding
      microbial production strains with a special emphasis on amino acid producers will
      be summarized.

PMID- 27872966
TI  - General Template for the FMEA Applications in Primary Food Processing.
AB  - Data on the hazards involved in the primary steps of processing cereals, fruit
      and vegetables, milk and milk products, meat and meat products, and fats and oils
      are compiled with a wide-ranging literature survey. After determining the common
      factors from these data, a general FMEA template is offered, and its use is
      explained with a case study on pasteurized milk production.

PMID- 27872967
TI  - L-Methionine Production.
AB  - L-Methionine has been used in various industrial applications such as the
      production of feed and food additives and has been used as a raw material for
      medical supplies and drugs. It functions not only as an essential amino acid but
      also as a physiological effector, for example, by inhibiting fat accumulation and
      enhancing immune response. Producing methionine from fermentation is beneficial
      in that microorganisms can produce L-methionine selectively using eco-sustainable
      processes. Nevertheless, the fermentative method has not been used on an
      industrial scale because it is not competitive economically compared with
      chemical synthesis methods. Presented are efforts to develop suitable strains,
      engineered enzymes, and alternative process of producing L-methionine that
      overcomes problems of conventional fermentation methods. One of the alternative
      processes is a two-step process in which the L-methionine precursor is produced
      by fermentation and then converted to L-methionine by enzymes. Directed efforts
      toward strain development and enhanced enzyme engineering will advance industrial
      production of L-methionine based on fermentation.

PMID- 27872968
TI  - New Functions and Potential Applications of Amino Acids.
AB  - Currently, several types of amino acids are being produced and used worldwide.
      Nevertheless, several new functions of amino acids have been recently discovered
      that could result in other applications. For example, oral stimulation by
      glutamate triggers the cephalic phase response to prepare for food digestion.
      Further, the stomach and intestines have specific glutamate-recognizing systems
      in their epithelial mucosa. Regarding clinical applications, addition of
      monosodium glutamate to the medicinal diet has been shown to markedly enhance
      gastric secretion in a vagus-dependent manner. Branched-chain amino acids (BCAAs)
      are the major components of muscles, and ingestion of BCAAs has been found to be
      effective for decreasing muscle pain. BCAAs are expected to be a solution for the
      serious issue of aging. Further, ingestion of specific amino acids could be
      beneficial. Glycine can be ingested for good night's sleep: glycine ingestion
      before bedtime significantly improved subjective sleep quality. Ingestion of
      alanine and glutamine effectively accelerates alcohol metabolism, and ingestion
      of cystine and theanine effectively prevents colds. Finally, amino acids could be
      used in a novel clinical diagnostic method: the balance of amino acids in the
      blood could be an indicator of the risk of diseases such as cancer. These newly
      discovered functions of amino acids are expected to contribute to the resolution
      of various issues.

PMID- 27872970
TI  - Neonicotinoids: Systemic Insecticides and Systematic Failure.

PMID- 27872969
TI  - Effects of Peanut Shell Biochar on the Adsorption of Cd(II) by Paddy Soil.
AB  - Soil from an experimental paddy field in southern China was incubated with peanut
      shell biochar to investigate effects of this additive on the adsorption and
      desorption characteristics of Cd(II) using batch methods. Incorporation of
      biochar increased adsorption of Cd(II) by the paddy soil at 20, 25, and 30
      degrees C; this trend was apparent both with increasing quantities of biochar and
      rising temperature. Incorporation of biochar primarily enhanced the non
      electrostatic adsorption of Cd(II). In addition, supplementation with biochar
      decreased the adsorption rate of Cd(II), which decreased with increasing
      quantities of biochar. The Langmuir constant b and Freundlich constant kf both
      increased with greater quantities of biochar at different temperatures.
      Adsorption of Cd(II) was an endothermic process and occurred spontaneously.
      Incorporation of biochar decreased availability and mobility of Cd(II) to plants
      primarily through increased non-electrostatic adsorption of Cd(II) by paddy soil.

PMID- 27872971
TI  - The Influence of Nitrogen on the Biological Properties of Soil Contaminated with
      Zinc.
AB  - This study analyzed the relationship between nitrogen fertilization and the
      biological properties of soil contaminated with zinc. The influence of various
      concentrations of zinc and nitrogen on the microbiological and biochemical
      activity of soil was investigated. In a laboratory experiment, loamy sand with
      pHKCl 5.6 was contaminated with zinc (ZnCl2) and fertilized with urea as a source
      of nitrogen. The activity of acid phosphatase, alkaline phosphatase, urease and
      beta-glucosidase, and microbial counts were determined in soil samples after 2
      and 20 weeks of incubation. Zinc generally stimulated hydrolase activity, but the
      highest zinc dose (1250 mg kg-1) led to the inhibition of hydrolases. Nitrogen
      was not highly effective in neutralizing zinc's negative effect on enzyme
      activity, but it stimulated the growth of soil-dwelling microorganisms. The
      changes in soil acidity observed after the addition of urea modified the
      structure of microbial communities.

PMID- 27872973
TI  - Persistent Mercury Contamination in Shooting Range Soils: The Legacy from Former
      Primers.
AB  - Mercury (Hg) compounds were used in the past in primers for rifle and handgun
      ammunition. Despite its toxicity, little is known about the contamination of
      shooting-range soils with this metal. We present new data about the Hg
      contamination of surface soils from numerous shooting ranges of Switzerland. Our
      study demonstrates that Hg is measurable at high levels in surface soils from the
      shooting ranges. In three of the investigated ranges, concentrations above the
      maximum Swiss guidance value of Hg in soil of 500 ug kg-1 were measured. Since
      the use of mercury-containing ammunition was stopped in the 1960s, our results
      demonstrate the high persistence of Hg in soils and their slow recovery by
      natural mechanisms.

PMID- 27872972
TI  - Characteristics, Sources and Health Risk Assessment of Trace Metals in PM10 in
      Panzhihua, China.
AB  - Ambient PM10 air samples were collected at two industrial sites and one urban
      residential site in the mining city of Panzhihua, China, from April, 2014, to
      January, 2015. Mass concentrations of ten trace metals (As, Cd, Cr, Ni, Co, V,
      Mn, Cu, Pb, and Zn) in PM10 were determined by inductively coupled plasma-mass
      spectrometry. The results showed Zn, Pb, Cu, Mn and V were the most abundant
      elements from the industrial sites. Concentrations for Cd, Cr, Co, Ni, Mn and Cu
      at industrial sites greatly exceeded the air quality standards of the World
      Health Organization and the Chinese Ministry of Environmental Protection.
      Principal component analysis indicated that the main sources of the trace metals
      were steel smelting, fuel combustion, geological and mineral dust. Four different
      clusters of particles (i.e., mineral, calcium-containing, soot and
      aluminosilicate) were identified by scanning electron microscopy coupled with
      energy dispersive X-ray spectrometry. Chromium (Cr) was found to present the
      highest excess cancer risk, implying the potential for carcinogenic health
      effects in local inhabitants. Manganese (Mn) presented a non-carcinogenic health
      risk to children and adults, while the other metals were within acceptable
      limits.

PMID- 27872974
TI  - Interest of Using Ropivacaine for Outpatient Laparoscopic Cholecystectomy:
      Prospective Randomized Trial.
AB  - BACKGROUND: The objective of this study was to evaluate the interest of using
      ropivacaine for outpatient laparoscopic cholecystectomy. The use of local
      anesthesia by instillation and infiltration could reduce pain and increase the
      number of outpatient cholecystectomies. METHODS: A one-center randomized
      prospective clinical trial compared the use of ropivacaine during outpatient
      laparoscopic cholecystectomy to the control group of outpatients for laparoscopic
      cholecystectomy between April 2014 and May 2015. One hundred twenty-four were
      eligible, and 100 patients were randomized. Patients with outpatient
      cholecystectomy were randomized into 2 groups: ropivacaine group (Rop group) and
      control group (control group). We performed a ropivacaine intraperitoneal
      instillation and wound infiltration for the ropivacaine group at the end of the
      procedure. The primary observation was authorization for home discharge. The
      patient was evaluated by the surgeon using the Chung score. Secondary
      observations included postoperative pain at 2 h post-surgery, at 6 h post-surgery
      and the day following surgery. RESULTS: Ninety-eight were able to leave on the
      evening of surgery. At 6 h post-surgery, the Chung score was identical for both
      groups (p = 0.73). At 2 and 6 h post-surgery and the day following surgery, there
      was no significant difference in pain levels (p = 0.63; p = 0.61; p = 0.98).
      Analgesic consumption was no significant difference in the groups. CONCLUSIONS:
      The use of ropivacaine does not increase the rate of home discharge and does not
      change the postoperative pain of outpatient cholecystectomy.

PMID- 27872975
TI  - Identification of Recurrence-Predictive Indicators in Stage I Colorectal Cancer.
AB  - BACKGROUND: Patients with stage I colorectal cancer (CRC) rarely experience
      recurrences; therefore, few risk factors for recurrence are known. This study was
      designed to evaluate oncologic outcomes of patients with stage I CRC and to
      identify risk factors for recurrence after curative surgery. METHODS: A
      retrospective cohort of 860 patients from a single institution who underwent
      curative surgery for stage I CRC between July 1995 and June 2010 was enrolled.
      Patients who were diagnosed with hereditary, synchronous, or metachronous cancer
      and those who received preoperative chemoradiotherapy were excluded. Patients
      from whom fewer than 12 lymph nodes were retrieved were also excluded. RESULTS:
      The 860 patients included 402 (46.7%) with colon tumors and 458 (53.3%) with
      rectal tumors. Thirty-five patients (4.1%) experienced recurrences; local and
      systemic recurrence rates were 1.1 and 3.0%, respectively. The 5-year overall
      survival and recurrence-free survival (RFS) rates were 93.5 +/- 0.8% and 95.7 +/-
      0.8%, respectively. Multivariate analysis showed that preoperative serum
      carcinoembryonic antigen (CEA) concentration >=6 ng/mL (hazard ratio [HR] 3.354,
      95% confidence interval [CI] 1.373-8.195, p = 0.008) and lymphovascular invasion
      (LVI) (HR 2.676, 95% CI 1.097-6.531, p = 0.031) were independent risk factors for
      RFS. CONCLUSIONS: The overall recurrence rate among patients with stage I CRC
      after curative surgery was 4.1%. Elevated serum CEA and LVI were significantly
      associated with recurrence. Large-scale, multicenter studies are needed to
      confirm the prognostic value of these risk factors.

PMID- 27872976
TI  - Development and Validation of a Scoring System to Predict Surgical Site Infection
      After Ventral Hernia Repair: A Michigan Surgical Quality Collaborative Study.
AB  - INTRODUCTION: Surgical site infections (SSIs) are a rare but significant
      complication following an elective ventral hernia repair. This study aims to
      develop a risk assessment tool in order to predict the risk of developing SSIs
      postoperatively. METHODS: All patients undergoing an elective ventral hernia
      repair were identified using the Michigan Surgical Quality Collaborative (MSQC)
      database. Patients' demographics, comorbidities and technical aspects of the
      operations were extracted. Logistic regressions were used to create a predictive
      scoring system for SSIs. RESULTS: A total of 4983 were included. SSIs occurred in
      3.4% of the patient population. A stepwise forward logistic regression identified
      the need to use drains, BMI, wound classification at the end of the surgery,
      presence of severe adhesions, a history of CAD, the need for intensive care after
      surgery, the use of pressors, EtOH abuse and history of PVD as being
      independently associated with the development of postoperative surgical site
      infections. CONCLUSION: In patients undergoing an elective hernia repair, the
      incidence of SSI is low. Several preoperative and perioperative factors can
      contribute to the development of SSIs.

PMID- 27872978
TI  - Introduction from the new Editors-in-Chief.

PMID- 27872977
TI  - Hypertension Cure Following Laparoscopic Adrenalectomy for Hyperaldosteronism is
      not Universal: Trends Over Two Decades.
AB  - BACKGROUND: Laparoscopic adrenalectomy has been established as a standard
      surgical method for unilateral primary aldosteronism. Meanwhile, the background
      characteristics of the patients undergoing adrenalectomy have changed over the
      last 20 years. The aim of this study was to investigate the changes in
      hypertension cure rates after laparoscopic adrenalectomy during the last two
      decades. METHODS: This retrospective clinical study included 176 patients who
      underwent unilateral laparoscopic adrenalectomy for primary aldosteronism from
      1995 to 2015. The patients were divided into two groups by decade. The patients'
      baseline characteristics and the hypertension cure rates were compared between
      the two groups. Additionally, the values were re-examined based on predictive
      model predicting postoperative hypertension cure. RESULTS: The hypertension cure
      rate decreased significantly from 51.8 to 31.1%. The following variables were
      significantly different between the two groups: age, sex, body mass index,
      history of diabetes mellitus, preoperative systolic and diastolic blood
      pressures, potassium level, and plasma renin activity. CONCLUSIONS: This study
      showed that the number of patients with unfavorable conditions for hypertension
      cure after adrenalectomy has recently increased. The treatment goal for primary
      aldosteronism is not only to cure the hypertension but also to prevent organ
      disorders due to inappropriate aldosterone levels. Therefore, we recommend
      laparoscopic adrenalectomy for unilateral primary aldosteronism, even if
      hypertension is not always cured postoperatively. However, clinicians need to
      fully explain the postoperative hypertension outcomes to primary aldosteronism
      patients.

PMID- 27872979
TI  - Evaluation of isolated urinary stress incontinence according to the type of
      levator ani muscle lesion using 3/4D transperineal ultrasound 36 months post
      partum.
AB  - INTRODUCTION: Vaginal delivery can lead to pelvic floor disorders. Many authors
      have described pelvic floor injuries that can predict future defects such as
      urinary incontinence and pelvic organ prolapse. We propose the assessment of
      urinary stress incontinence and its association with levator ani muscle (LAM)
      microtrauma (>20% in the levator hiatus area during Valsalva) and macrotraumas
      (avulsion) identified by 3/4D transperineal ultrasound (3D-TpUS) 36 months post
      partum. MATERIALS AND METHODS: This was a prospective observational study
      including 168 nulliparous women. All patients included were nulliparous with
      singleton gestation in cephalic presentation, at >=37 weeks and were recruited on
      the first day after delivery. Thirty-six months after delivery, 3D-TpUS was
      carried out to identify LAM lesions (macro or micro). Clinical assessment of
      urinary stress incontinence (USI) was based on the ICIQ-UI-SF test; a simple
      stress test and urodynamic test were carried out in the same visit. RESULTS: A
      total of 105 nulliparous women were studied (51 spontaneous deliveries [SpD] and
      54 vacuum-assisted deliveries [VD]). Microtraumas were identified in 35.3% of SpD
      and 20.4% of VD. Macrotraumas (avulsion) were identified in 9.8% of SpD and 35.2%
      of VD (p = 0.006). No differences were found in USI between study groups or in
      relation to the identification of LAM defects (19.2% in the no lesion group, 25%
      in the macrotrauma and 13.8% in the microtrauma groups; p = not significant). Nor
      were significant differences found in the results from the different study groups
      in the International Consultation on Incontinence Modular Questionnaire Urinary
      Incontinence Short Form (ICIQ-UI SF) test (12.7+/-2.2 in the no lesion group,
      12.5+/-4.2 in the macrotrauma and 13.25+/-4.8 in the microtrauma groups; p = NS).
      CONCLUSION: No difference was observed in USI between patients with and without
      LAM lesions (microtrauma or macrotrauma) 36 months post-delivery.

PMID- 27872980
TI  - Preliminary results of managing large medial tibial defects in primary total knee
      arthroplasty: autogenous morcellised bone graft.
AB  - PURPOSE: This study reports a case series of 44 primary total knee arthroplasties
      (TKAs) using autogenous morcellised bone grafting for large (>=10-mm-deep) medial
      tibial defects, which are generally repaired using metal augmentation. The bone
      grafting technique is described in detail and the radiological outcomes are
      presented. METHODS: A total of 44 TKAs were followed up for a mean period of 58
      months (range 24-139 months). Multiple drill holes were made in the sclerotic
      floor of the defect, followed by the impaction of morcellised cancellous bone
      grafts to fill the defects. Tibial components were fixed using the cemented or
      noncemented technique and no internal fixation devices were used. Stem extension
      of the tibial component was only used in one TKA. RESULTS: Radiograms revealed
      that the grafted bone was completely incorporated into the host bone within one
      year post-operatively. No grafted bone absorption or collapse was detected. A
      clear zone between the tibial component and grafted bone was observed in six
      knees, but it did not become enlarged thereafter. CONCLUSIONS: The presented
      technique provided favourable radiological outcomes and had several advantages:
      (1) it enables preservation of as much bone as possible for future revision
      surgery; (2) it is cost effective and simple because metal augments, internal
      fixation devices and stem extension are not needed; (3) it can be used in the
      same manner any defect to a depth >=3 mm. Thus, this is an acceptable and
      reproducible alternative technique.

PMID- 27872981
TI  - Dual-mobility arthroplasty failure: a rationale review of causes and technical
      considerations for revision.
AB  - PURPOSE: Dual-mobility arthroplasty is an alternative to conventional total hip
      arthroplasty (THA) in appropriately selected, active adults with degenerative,
      necrotic or post-traumatic hip disease or with revision hip arthroplasty.
      Numerous papers have been published with results of dual-mobility arthroplasty,
      but there have been no comprehensive literature reviews that summarise the most
      recent findings and help the orthopaedic surgeon facing different scenarios in
      which revision of one or both components of a dual-mobility arthroplasty is
      indicated. METHODS: We performed a PubMed search for papers published on dual
      mobility arthroplasty that provided data on revision and add our experience in
      order to describe different revision scenarios. We collected data on revision for
      any reason, for aseptic loosening, for infection, or for dislocation. For each
      complication, we summarise causes and diagnosis of this complication and describe
      the direction of possible therapeutic options. RESULTS: The dual-mobility
      arthroplasty offers the benefit of increased stability without compromising
      clinical outcomes and implant longevity. However, as with conventional
      arthroplasties, complications are also reported, with the most frequent being cup
      loosening, dislocation, accelerated wear and infection. Dual-mobility implants
      also have some specific complications secondary to their specific design, with
      the presence of a third joint. For example, intraprosthetic dislocation due to
      retentive failure of the polyethylene (PE) liner on the femoral head is a
      complication observed exclusively with this type of implant and involves
      articulation failure between the femoral head and the PE liner. Mechanical
      conflict with the iliopsoas tendon has also been reported, probably due to
      femoral head size, cup design, and/or a dysplastic hip. This systematic review of
      the literature identified several options for treating each complication, and in
      particular, options regarding conserving or not of one the two articulating
      devices. CONCLUSIONS: These findings can inform discussions relating to risks and
      benefits of different therapeutic options when performing revision of a dual
      mobility arthroplasty.

PMID- 27872983
TI  - Robotic-Assisted Versus Manual Prostatic Arterial Embolization for Benign
      Prostatic Hyperplasia: A Comparative Analysis.
AB  - PURPOSE: Prostatic artery embolization (PAE) is a safe and efficacious procedure
      for benign prostatic hyperplasia (BPH), though is technically challenging. We
      present our experience of technical and clinical outcomes of robotic and manual
      PAE in patients with BPH. MATERIALS AND METHODS: IRB-approved retrospective study
      of 40 consecutive patients 49-81 years old with moderate or severe grade BPH from
      May 2014 to July 2015: 20 robotic-assisted PAE (group 1), 20 manual PAE (group
      2). Robotic-assisted PAE was performed using the Magellan Robotic System.
      American Urological Association (AUA-SI) score, cost, technical and clinical
      success, radiation dose, fluoroscopy, and procedure time were reviewed.
      Statistical analysis was performed within and between each group using paired t
      test and one-way analysis of variance respectively, at 1 and 3 months. RESULTS:
      No significant baseline differences in age and AUA-SI between groups. Technical
      success was 100% (group 1) and 95% (group 2). One unsuccessful subject from group
      2 returned for a successful embolization using robotic assistance. Fluoroscopy
      and procedural times were similar between groups, with a non-significant lower
      patient radiation dose in group 1 (30,632.8 mGy/cm2 vs 35,890.9, p = 0.269).
      Disposable cost was significantly different between groups with the robotic
      assisted PAE incurring a higher cost (group 1 $4530.2; group 2 $1588.5, p <
      0.0001). Clinical improvement was significant in both arms at 3 months: group 1
      mean change in AUA-SI of 8.3 (p = 0.006), group 2: 9.6 (p < 0.0001). No minor or
      major complications occurred. CONCLUSIONS: Robotic-assisted PAE offers technical
      success comparable to manual PAE, with similar clinical improvement with an
      increased cost.

PMID- 27872982
TI  - Interplay between Top1 and Mms21/Nse2 mediated sumoylation in stable maintenance
      of long chromosomes.
AB  - Genetic information in cells is encrypted in DNA molecules forming chromosomes of
      varying sizes. Accurate replication and partitioning of chromosomes in the
      crowded cellular milieu is a complex process involving duplication, folding and
      movement. Longer chromosomes may be more susceptible to mis-segregation or DNA
      damage and there may exist specialized physiological mechanisms preventing this.
      Here, we present genetic evidence for such a mechanism which depends on
      Mms21/Nse2 mediated sumoylation and topoisomerase-1 (Top1) for maintaining
      stability of longer chromosomes. While mutations inactivating Top1 or the SUMO
      ligase activity of Mms21 (mms21sl) individually destabilized yeast artificial
      chromosomes (YACs) to a modest extent, the mms21sl top1 double mutant exhibited a
      synthetic-sick phenotype, and showed preferential destabilization of the longer
      chromosome relative to shorter chromosomes. In contrast, an smc6-56 top1 mutant
      defective in Smc6, another subunit of the Smc5/6 complex, of which Mms21 is a
      component, did not show such a preferential enhancement in frequency of loss of
      the longer YAC, indicating that this defect may be specific to the deficiency in
      SUMO ligase activity of Mms21 in the mms21sl top1 mutants. In addition, mms21sl
      top1 double mutants harboring a longer fusion derivative of natural yeast
      chromosomes IV and XII displayed reduced viability, consistent with enhanced
      chromosome instability, relative to single mutants or the double mutant having
      the natural (shorter) non-fused chromosomes. Our findings reveal a functional
      interplay between Mms21 and Top1 in maintenance of longer chromosomes, and
      suggest that lack of sumoylation of Mms21 targets coupled with Top1 deficiency is
      a crucial requirement for accurate inheritance of longer chromosomes.

PMID- 27872985
TI  - Pharmacokinetics and Histopathological Findings of Chemoembolization Using
      Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver
      Tumor Model.
AB  - PURPOSE: The purpose of this study is to evaluate the pharmacokinetics and
      histopathological findings of transarterial chemoembolization (TACE) using
      cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE)
      compared with cisplatin arterial infusion (Cis-AI). MATERIALS AND METHODS:
      Eighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE
      (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of
      cisplatin powder and DSM was injected until stasis of hepatic arterial flow was
      achieved. In the Cis-AI group, cisplatin solution was infused. RESULTS: The
      platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h
      were significantly elevated compared with those in the Cis-AI group (P = .016 and
      .019, respectively). There were no significant differences in the platinum
      concentrations in plasma. Histopathological examination revealed the presence of
      several microspheres inside the tumors at 1 h, which completely disappeared at 24
      h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently
      observed compared with that in the Cis-AI group (P = .006). CONCLUSIONS: TACE
      using cisplatin powder mixed with DSM provides a higher drug concentration in
      tumors, thereby achieving stronger antitumor effects compared with arterial
      infusion of cisplatin solution.

PMID- 27872984
TI  - Cinnamic Acid Derivatives Enhance the Efficacy of Transarterial Embolization in a
      Rat Model of Hepatocellular Carcinoma.
AB  - INTRODUCTION: We hypothesize that the combination of transarterial embolization
      (TAE) plus inhibition of lactate export will limit anaerobic metabolism and
      reduce tumor survival compared to TAE alone. The purpose of this study was to
      test this hypothesis in a rat model of hepatocellular carcinoma (HCC). METHODS:
      Rat N1-S1 hepatoma cells were assayed in vitro using the Seahorse XF analyzer to
      measure extracellular acidification (lactate excretion) comparing effects of the
      addition of caffeic acid (CA) or ferulic acid (FA) or UK-5099 with control.
      Monocarboxylate transporter Slc16a3 was knocked down by RNAi. N1S1 tumors were
      orthotopically implanted in rats and 4 groups evaluated: (1) Control, (2) TAE
      only, (3) TAE plus CA, and (4) TAE plus FA. Tumor size was determined by
      ultrasound and analyzed by repeated measures statistics. Tumors harvested at 4
      weeks were examined by microscopy. RESULTS: Seahorse assays showed that CA and FA
      caused a significant reduction by >90% in lactate efflux by N1S1 tumor cells (p <
      0.01). Knockdown of Slc16a3 prevented inhibition by CA. In vivo tumors grew 30
      fold in volume over 4 weeks in untreated controls. By comparison, TAE resulted in
      near cessation of growth (10% in 4-week time period). However, both TAE + CA and
      TAE + FA caused a significant reduction of tumor volumes (87 and 72%,
      respectively) compared to control and TAE (p < 0.05). Pathologic evaluation
      revealed residual tumor in the TAE group but no residual viable tumor cells in
      the TAE + CA and TAE + FA groups. CONCLUSION: Addition of CA or FA enhances the
      effectiveness of TAE therapy for HCC in part by blocking lactate efflux.

PMID- 27872987
TI  - The IR Evolution in Oncology: Tools, Treatments, and Guidelines.
AB  - Early focus of interventional oncologists was developing tools and imaging
      guidance, performing "procedures" acting as a skillful technician without
      knowledge of clinical patient outcomes, beyond post-treatment image findings.
      Interventional oncologists must deliver "treatments" and not "procedures", and
      focus on clinically relevant outcomes, provide clinical continuity of care, which
      means stand at multidisciplinary tumor boards, see patients in consultation
      before treatment and for follow-up. Interventional oncologists have fought for
      the same "market" with surgery in a head to head, bloody competition called red
      ocean strategy in marketing terms, resulting in many aborted trials. Wide
      adoption of interventional oncology is facing the challenge to build evidence
      with overall survival as endpoint in randomized trials while the benefits of a
      treatment on overall survival are diluted by the effects of possible/inevitable
      subsequent therapies. Because interventional oncology is a disruptive force in
      medicine achieving same results as others (surgery) using different, less
      invasive approaches, patients where surgery is irrelevant can be target with a
      blue ocean strategy (to propose treatment where there is no competition).
      Recently interventional oncology has been included in the ESMO guidelines for
      colorectal cancer with oligometastatic disease with both surgical resection, and
      thermal ablation classified in the same category called "local ablative
      treatments". Interventional oncologists have to shape the future by publications
      in oncologic journal, by being active members of oncology scientific societies,
      and use modern public megaphone (blog, video sharing, ...) to disseminate
      information and let society know that interventional is not a me-too product but
      a disruptive treatment.

PMID- 27872986
TI  - Prostate Zonal Volumetry as a Predictor of Clinical Outcomes for Prostate Artery
      Embolization.
AB  - PURPOSE: To determine prostate baseline zonal volumetry and correlate these
      findings with clinical outcomes for patients who underwent prostate artery
      embolization (PAE) for lower urinary tract symptoms (LUTS) due to benign
      prostatic hyperplasia (BPH). MATERIALS AND METHODS: This is a retrospective study
      that included patients treated by PAE from 2010 to 2014. Baseline and 6-month
      follow-up evaluations included prostate MRI with whole prostate (WP) and central
      gland (CG) volume measurements-as well as prostate zonal volumetry index (ZVi)
      calculation, defined as the CG/WP volumes relation-the International Prostate
      Symptom Score (IPSS), and the Quality of life (QoL) index. Baseline WP, CG, and
      ZVi were statistical compared to IPSS and QoL values at 6 months. RESULTS: A
      total of 93 consecutive patients were included, with mean age of 63.4 years
      (range, 51-86). Clinical failure, defined as IPSS > 7 or QoL > 2, was seen in
      four cases (4.3%). Mean reductions in prostate volumes after PAE were of 30.6%
      and 31.2% for WP and CG, respectively (p < 0.0001). Clinical parameters had mean
      decrease from 21 to 3.3 points for IPSS, and from 4.7 to 1.2 points for QoL (p <
      0.0001). Baseline WP, CG, and ZVi correlated to the degree of clinical
      improvement (p < 0.05 for all). The baseline ZVi cut-off calculated for better
      clinical outcomes was > 0.45, with 85% sensitivity and 75% specificity.
      CONCLUSIONS: Baseline CG and WP volumes as well as ZVi presented strong
      correlation with clinical outcomes in patients undergoing PAE, and its assessment
      should be considered in pre-treatment evaluation whenever possible. Both patients
      and medical team should be aware of the possibility of less favorable outcomes
      when ZVi < 0.45.

PMID- 27872988
TI  - Prostatic Arterial Embolization Treating Moderate-to-Severe Lower Urinary Tract
      Symptoms Related to Benign Prostate Hyperplasia: A Meta-Analysis.
AB  - PURPOSE: To evaluate the clinical efficiency and safety of PAE treating moderate
      to-severe LUTS related to BPH. MATERIALS AND METHODS: A systematic literature
      search was performed using PUBMED, EMBASE, Cochrane database of systematic
      review, and Web of Science, up to April 2016, to identify eligible studies. The
      Cochrane Collaboration's RevMan 5.3 was used to analyze the extracted data.
      Random- or fixed-effect model was selected to fit the pooled out heterogeneity.
      RESULTS: 20 eligible studies were included in this meta-analysis. Synthetic data
      showed that there were statistically significant improvements in IPSS (MD = 
      13.25; 95% CI -14.81 to -11.69; P < 0.00001), QoL score (MD = -2.34; 95% CI -2.69
      to -2.00, P < 0.00001), PSA level (MD = -1.33; 95% CI -1.86 to -0.80; P <
      0.00001), PV (MD = -28.00; 95% CI -35.94 to -20.07; P < 0.00001), Qmax (MD =
      5.51; 95% CI 4.62 to 6.40; P < 0.00001), and PVR (MD = -67.8; 95% CI -81.35 to 
      53.60; P < 0.00001). There was no significant difference in IIEF score (MD =
      0.93; 95% CI 0.43-1.42; P = 0.07). Major complications following PAE include pain
      in the perineum, retropubic area, and/or urethra (9.4%), and hematuria (9.0%).
      CONCLUSIONS: PAE should be considered to be the very promising alternative
      treatment for those who do not want or cannot tolerate surgical treatment, with
      its benefits on IPSS, QoL score, PSA level, PV, Qmax, and PVR without affecting
      erectile function.

PMID- 27872989
TI  - Is the contralateral tibia a reliable template for reconstruction: a three
      dimensional anatomy cadaveric study.
AB  - PURPOSE: The contralateral anatomy is regularly used as a reconstruction template
      for corrective osteotomies of several deformities and pathological conditions.
      However, there is lack of evidence that the intra-individual differences between
      both tibiae are sufficiently small to use the contralateral tibia as a 3D
      reconstruction template for complex osteotomies. The aim of this study was to
      evaluate the intra-individual side differences of the tibia in length, torsion,
      angulation, and translation using 3D measurement techniques. METHODS: 3D surface
      models of both tibiae were created from computed tomography data of 51 cadavers.
      The (mirrored) models of the right tibiae were divided into two halves at the
      centre of the shaft. Thereafter, the proximal and distal segments were aligned to
      the left (contralateral) tibia in an automated fashion. The relative 3D
      transformation between both aligned segments was measured to quantify the side
      difference in 6 degrees  of freedom (3D translation vector, 3 angles of
      rotation). RESULTS: The mean side difference in tibia length was 2.1 mm (SD 1.3
      mm; range 0.2-5.9 mm). The mean side difference in torsion was 4.9 degrees  (SD
      4.1 degrees ; range 0.2 degrees -17.6 degrees ). The mean side difference in the
      coronal and sagittal planes was 1.1 degrees  (SD 0.9 degrees ; range 0.0 degrees 
      4.6 degrees ) and 1.0 degrees  (SD 0.8 degrees ; range 0.1 degrees -2.9 degrees
      ), respectively. CONCLUSION: The present study confirms small side differences in
      torsion between the left and right tibia, while the side differences in the
      coronal and sagittal plane are probably negligible. The contralateral tibia seems
      to be a reliable reconstruction template for the 3D preoperative planning of
      complex corrective osteotomies of the tibia. However, torsional differences
      should be interpreted with caution, as a single cut-off value of a clinically
      relevant torsional side difference cannot be defined. The presented results are
      relevant to surgeons considering the contralateral tibia as a 3D reconstruction
      template for corrective osteotomies of the tibia. LEVEL OF EVIDENCE: Basic
      science.

PMID- 27872990
TI  - Blood supply of the subacromial bursa and rotator cuff tendons on the bursal
      side.
AB  - PURPOSE: Vascularity of the subacromial bursa and rotator cuff tendons is key
      factors in the pathogenesis of subacromial bursitis and impingement syndrome,
      rotator cuff tendinitis, and rotator cuff tears. The purpose of this study was to
      investigate and describe blood supply to the cranial and caudal parts of the
      subacromial bursa and the vascularity of the rotator cuff tendons on the bursal
      side. METHODS: Fourteen fresh cadaveric shoulders from six females and eight
      males with a mean age of 71.7 (+/-10.8) years were studied. Before dissection, an
      arterial injection of 10% aqueous dispersion of latex was administered. Post
      injection, the shoulders were fixed in an alcohol-formalin-glycerol solution.
      RESULTS: The cranial and caudal bursa of all specimens was mainly supplied by the
      thoracoacromial, suprascapular, and anterior and posterior circumflex humeral
      arteries. The cranial part of the bursa was supplied anteriorly by the
      thoracoacromial artery, and posteriorly and medially by the posterior circumflex
      humeral artery as far as the medial third. The caudal part received arterial
      blood anteriorly from the anterior circumflex humeral artery, and posteriorly and
      medially by the posterior circumflex humeral artery as far as the medial third of
      the caudal bursa. In addition, the suprascapular artery branched at the upper
      surface of the coracohumeral ligament, and the subcoracoid artery branched at the
      under surface of the same ligament. CONCLUSION: The subacromial bursa appears
      well vascularized. The results of the present investigation showed that blood
      supply to the subacromial bursa at the caudal part and rotator cuff tendons on
      the bursal side was linked to the same arteries. The subcoracoid artery supplied
      interval rotator structures close to the caudal bursa. It is the wish of the
      authors that this meticulous anatomical work will help surgeons in their day-to
      day clinical work, e.g. to minimize the risk of complications such as
      perioperative bleeding.

PMID- 27872991
TI  - Shoulder manual muscle resistance test cannot fully detect muscle weakness.
AB  - PURPOSE: The shoulder manual resistance test is one of the common clinical
      assessments for patients with muscle weakness. However, there have been no
      studies investigating the threshold for muscle weakness. The purpose of this
      study was to clarify the threshold for muscle weakness in the shoulder manual
      muscle resistance test. METHODS: Fifty-three patients (37.9 +/- 20.6 years old)
      with either rotator cuff tear (21 patients), superior labrum anterior-to
      posterior (SLAP) lesion (7 patients), or Bankart lesion (25 patients) of one
      shoulder were administered three manual muscle resistance tests (abduction
      strength, external rotation, and belly press tests). Positive results in these
      tests were defined as a subjective weakness in the involved shoulder compared to
      the opposite shoulder. Based on this result, the patients were divided into
      positive and negative groups. Another observer measured isometric strength using
      a hand-held dynamometer and calculated the side-to-side ratio. Comparing
      instrument measurement with manual measurement, the cut-off point, at which we
      can recognise that there is a side-to-side difference, was calculated by receiver
      operating characteristic analysis. RESULTS: The cases with less than 60% of the
      muscle strength in the contralateral shoulder were judged as positive in all
      examinations, whereas among the cases with 60-90% of muscle strength, there was a
      mixture of negative and positive determinations. The cut-off point was 78.9% in
      the abduction strength test, 73.8% in the external rotation test, and 84.0% in
      the belly press test. CONCLUSION: The side-to-side difference could be manually
      detected, when muscle strength was less than 75-85% of that on the contralateral
      side. This finding suggests that it is necessary to understand the limitation of
      these manual tests in the case of clinical examinations. Therefore, care must be
      taken for the shoulder manual muscle resistance test as muscle weakness cannot be
      fully detected by manual measurement. LEVEL OF EVIDENCE: Case-control study,
      Level IV.

PMID- 27872992
TI  - Atrial Septal Defect Closure with Occlutech(r) ASD Fenestrated Device in a Child
      with Severe Pulmonary Hypertension.
AB  - We report a 5-year-old patient with severe pulmonary hypertension and a large
      secundum atrial septal defect who benefited from a percutaneous closure of the
      defect with an Occlutech(r) custom-made fenestrated device. Whereas the closure
      is technically identical to standard atrial defect closure, the immediate and
      midterm beneficial results are presented.

PMID- 27872993
TI  - Cardiac Catheterization in Pediatric Patients Supported by Extracorporeal
      Membrane Oxygenation: A 15-Year Experience.
AB  - Cardiac catheterization is commonly performed in patients being supported by
      extracorporeal membrane oxygenation (ECMO). We aimed to evaluate the safety,
      benefit, and outcomes of catheterization in pediatric patients supported by ECMO.
      Retrospective review of cardiac catheterizations performed in patients <=18 years
      of age while on ECMO at a large tertiary care center between January 2000 and May
      2015. A total of 55 catheterizations were performed on 51 patients during 53
      unique ECMO courses. Indications for ECMO include ventricular dysfunction (22),
      cardiac arrest (20), inability to wean from cardiopulmonary bypass (7), and
      persistent cyanosis (4). Catheterizations included purely diagnostic studies
      (11), atrial septostomies (34), stenting of vessels or surgical shunts (6),
      adjustment of a stent (1), coil embolization (1), and endomyocardial biopsy (1).
      Septostomy was elective in 58.8% of cases (20) and emergent in 41.2% (14). Forty
      six catheterizations had either surgical or catheter intervention during the same
      or subsequent study (83.6%). High severity complications occurred in three
      patients (5.6%), including one death due to hemothorax after pulmonary artery
      stent placement. There were no complications during patient transport. In total,
      38 out of 53 (71.7%) ECMO courses resulted in decannulation, 29 (54.7%) patients
      survived to discharge from the hospital, and 25 (47.2%) were alive at follow-up.
      Cardiac catheterization can be safely performed on patients supported by ECMO.
      Cardiac catheterization is a critical tool in the early recognition, diagnosis,
      and direct treatment of hemodynamic/anatomic abnormalities in patients supported
      by ECMO.

PMID- 27872994
TI  - Outcomes of Tracheostomy in Children Requiring Surgery for Congenital Heart
      Disease.
AB  - Outcomes after discharge in children requiring tracheostomy after cardiac surgery
      have not been fully described. A retrospective, single-center study was performed
      on all children <18 years of age requiring both tracheostomy and surgery for
      congenital heart disease from January 2002 to May 2015. Forty-six tracheostomies
      were placed after surgery and four before. Single-ventricle anatomy was present
      in 12 (33%) patients. Incidence of tracheostomy after heart surgery increased
      from 0.8% the first half of the study period to 2% the second half. Median time
      between cardiac surgery and tracheostomy was 58 days. The most common indication
      for tracheostomy was multifactorial (30%) followed by airway malacia (22%).
      Median length to follow-up for survivors was 3.9 years (range 0.4-11.8 years).
      Survival to hospital discharge was 72%, and intermediate survival was 48%.
      Survival in those with systemic to pulmonary artery shunts at the time of
      tracheostomy was 22% compared to 59% for those with biventricular anatomy. Heart
      failure and multiple indications for tracheostomy were associated with worse
      outcome. There was no difference in survival for those discharged with a
      ventilator compared to those that were not. The most common cause of death after
      discharge was tracheostomy tube dislodgement/obstruction, accounting for 5 of 11
      that died. Survival with a tracheostomy after cardiac surgery is poor, and
      children with systemic to pulmonary artery shunts are at especially high risk of
      death.

PMID- 27872995
TI  - NT-proBNP as Marker of Ventricular Dilatation and Pulmonary Regurgitation After
      Surgical Correction of Tetralogy of Fallot: A MRI Validation Study.
AB  - The goal of this study is to evaluate whether NT-proBNP plasma levels may help as
      a screening biomarker for monitoring right ventricular dilatation, pulmonary
      regurgitation and the onset of heart failure in patients with repaired Tetralogy
      of Fallot. Our single-centre observational prospective study involved 43 patients
      (15.1 years, SD = 8) with corrected Tetralogy of Fallot. Data collection
      included: clinical parameters (electrocardiogram, chest X-ray, NYHA scale, time
      since last surgery), biochemistry (NT-proBNP levels) and MRI values (ventricular
      volumetry, pulmonary flow assessment). Mean time since last surgery was 13.5
      years (SD = 7.8). There was a statistically significant correlation between the
      NT-proBNP levels (187.4 pg/ml, SD = 154.9) and right ventricular dilatation for
      both the right ventricular end-diastolic volume (124.9 ml/m2, SD = 31.2) (Pearson
      = 0.19, p < 0.01) and end-systolic volume (56.1 ml/m2, SD = 18.8) (Pearson =
      0.21, p < 0.01) and also with the pulmonary regurgitation fraction (36.5%, SD =
      16, Pearson = 0.12, p < 0.01). No significant correlation was found between NT
      proBNP and right ventricular ejection fraction (54.6%, SD = 10.6, Pearson = 
      0.07), left ventricular ejection fraction (59.9%, SD = 7.1, Pearson = -0.18) or
      any clinical parameters. The receiver operating curve analysis evidenced that a
      NT-proBNP cut-off value above 133.2 pg/ml predicted the presence of dilated right
      ventricular end-diastolic and end-systolic volumes over centile 95 (sensitivity
      82 and 83% and specificity 93 and 79%, respectively). In conclusion, in patients
      with surgically corrected Tetralogy of Fallot, NT-proBNP levels correlate with
      right ventricular dilatation and the degree of pulmonary regurgitation.
      Ambulatory determination of NT-proBNP might be an easy, readily available and
      cost-effective alternative for MRI follow-up evaluation of these patients.

PMID- 27872996
TI  - Surgical Repair of Ventricular Septal Defect; Contemporary Results and Risk
      Factors for a Complicated Course.
AB  - Surgical closure of the ventricular septal defect is the most commonly performed
      procedure in pediatric cardiac surgery. There are conflicting data on weight at
      operation as risk factor for a complicated course. We performed a retrospective
      evaluation of mortality and morbidity in all patients undergoing surgical
      ventricular septal defect closure at our institution between 2004 and 2012 to
      identify risk factor for a complicated course. Multivariate logistic regression
      modeling was performed to identify risk factors for a complicated course. 243
      patients who underwent surgical ventricular septal defect closure were included.
      Median age at operation was 168.0 days (range 17-6898), the median weight 6.0 kg
      (range 2.1-102.0). No deaths occurred. Two patients (0.8%) required a pacemaker
      for permanent heart block. Five patients (2.1%) underwent reoperation for a
      hemodynamically important residual ventricular septal defect. No other major
      adverse events occurred. No risk factors for major adverse events could be
      established. Multivariate analysis identified a genetic syndrome, long bypass
      time and low weight at operation as independent risk factors for a prolonged
      intensive care stay (>1 day) and prolonged ventilation time (>6 h). Contemporary
      results of surgical VSD closure are excellent with no mortality and low morbidity
      in this series. Although it is associated with increased ventilation time and a
      longer hospital stay, low bodyweight at operation is not associated with an
      increased risk of complications or major adverse events in our series.

PMID- 27872997
TI  - Microarray (phylochip) analysis of freshwater pathogens at several sites along
      the Northern German coast transecting both estuarine and freshwaters.
AB  - Monitoring the quality of drinking water is an important issue for public health.
      Two of the main objectives of the European Project MUAQUA were (i) the
      development of specific probes to detect and quantify pathogens in drinking water
      and (ii) the design of standardized sampling programs of water from different
      sources in Europe in order to obtain sufficient material for downstream analysis.
      Our phylochip contains barcodes that specifically identify freshwater pathogens
      for enabling the detection of organisms that can be risks for human health.
      Monitoring for organisms with molecular tools is rapid, more accurate and more
      reliable than traditional methods. Rapid detection means that mitigation
      strategies come into play faster with less harm to the community and to humans.
      Samples were collected from several waters in France, Germany, Ireland, Italy and
      Turkey over 2 years. We present microarray results for the presence of freshwater
      pathogens from brackish and freshwater sites in Northern Germany, and
      cyanobacterial cell numbers inferred from these sites. In a companion study from
      the same samples, cyanobacterial toxins were analyzed using two methods and those
      sites with highest toxin values also had highest cell numbers as inferred from
      this microarray study.

PMID- 27872999
TI  - Laccase catalysis for the synthesis of bioactive compounds.
AB  - The demand for compounds of therapeutic value is increasing mainly because of new
      applications of bioactive compounds in medicine, pharmaceutical, agricultural,
      and food industries. This has necessitated the search for cost-effective methods
      for producing bioactive compounds and therefore the intensification of the search
      for enzymatic approaches in organic synthesis. Laccase is one of the enzymes that
      have shown encouraging potential as biocatalysts in the synthesis of bioactive
      compounds. Laccases are multicopper oxidases with a diverse range of catalytic
      activities revolving around synthesis and degradative reactions. They have
      attracted much attention as potential industrial catalysts in organic synthesis
      mainly because they are essentially green catalysts with a diverse substrate
      range. Their reaction only requires molecular oxygen and releases water as the
      only by-product. Laccase catalysis involves the abstraction of a single electron
      from their substrates to produce reactive radicals. The free radicals
      subsequently undergo homo- and hetero-coupling to form dimeric, oligomeric,
      polymeric, or cross-coupling products which have practical implications in
      organic synthesis. Consequently, there is a growing body of research focused on
      the synthetic applications of laccases such as organic synthesis, hair and
      textile dyeing, polymer synthesis, and grafting processes. This paper reviews the
      major advances in laccase-mediated synthesis of bioactive compounds, the
      mechanisms of enzymatic coupling, structure-activity relationships of synthesized
      compounds, and the challenges that might guide future research directions.

PMID- 27872998
TI  - PpEst is a novel PBAT degrading polyesterase identified by proteomic screening of
      Pseudomonas pseudoalcaligenes.
AB  - A novel esterase, PpEst, that hydrolyses the co-aromatic-aliphatic polyester
      poly(1,4-butylene adipate-co-terephthalate) (PBAT) was identified by proteomic
      screening of the Pseudomonas pseudoalcaligenes secretome. PpEst was induced by
      the presence of PBAT in the growth media and had predicted arylesterase (EC
      3.1.1.2) activity. PpEst showed polyesterase activity on both whole and milled
      PBAT film releasing terephthalic acid and 4-(4-hydroxybutoxycarbonyl)benzoic acid
      while end product inhibition by 4-(4-hydroxybutoxycarbonyl)benzoic acid was
      observed. Modelling of an aromatic polyester mimicking oligomer into the PpEst
      active site indicated that the binding pocket could be big enough to accommodate
      large polymers. This is the first report of a PBAT degrading enzyme being
      identified by proteomic screening and shows that this approach can contribute to
      the discovery of new polymer hydrolysing enzymes. Moreover, these results
      indicate that arylesterases could be an interesting enzyme class for
      identifications of polyesterases.

PMID- 27873000
TI  - Mercury alters the bacterial community structure and diversity in soil even at
      concentrations lower than the guideline values.
AB  - This study evaluated the effect of inorganic mercury (Hg) on bacterial community
      and diversity in different soils. Three soils-neutral, alkaline and acidic-were
      spiked with six different concentrations of Hg ranging from 0 to 200 mg kg-1 and
      aged for 90 days. At the end of the ageing period, 18 samples from three
      different soils were investigated for bacterial community structure and soil
      physicochemical properties. Illumina MiSeq-based 16s ribosomal RNA (rRNA)
      amplicon sequencing revealed the alteration in the bacterial community between un
      spiked control soils and Hg-spiked soils. Among the bacterial groups,
      Actinobacteria (22.65%) were the most abundant phyla in all samples followed by
      Proteobacteria (21.95%), Bacteroidetes (4.15%), Firmicutes (2.9%) and
      Acidobacteria (2.04%). However, the largest group showing increased abundance
      with higher Hg doses was the unclassified group (45.86%), followed by
      Proteobacteria. Mercury had a considerable negative impact on key soil functional
      bacteria such as ammonium oxidizers and nitrifiers. Canonical correspondence
      analysis (CCA) indicated that among the measured soil properties, Hg had a major
      influence on bacterial community structure. Furthermore, nonlinear regression
      analysis confirmed that Hg significantly decreased soil bacterial alpha diversity
      in lower organic carbon containing neutral and alkaline soils, whereas in acidic
      soil with higher organic carbon there was no significant correlation. EC20 values
      obtained by a nonlinear regression analysis indicated that Hg significantly
      decreased soil bacterial diversity in concentrations lower than several guideline
      values.

PMID- 27873001
TI  - 1,2-Dimethylimidazole-4-sulfonyl chloride (DMISC), a novel derivatization
      strategy for the analysis of propofol by LC-ESI-MS/MS.
AB  - Analysis of the anesthetic agent propofol in biological samples by LC-MS/MS is a
      great challenge due to weak fragmentation and poor ionization efficacy of
      propofol resulting in weak signal intensities. Improvements of the ionization and
      fragmentation efficacy can be achieved by conversion of propofol to its
      dimethylimidazolesulfonyl (DMIS) derivative by a derivatization reaction using
      1,2-dimethylimidazole-4-sulfonyl chloride (DMISC). This DMIS derivative produced
      intense [M + H]+ ions in positive-ion LC-ESI-MS/MS with the dimethylimidazole
      moieties representing the most abundant product ions. Derivatization of serum
      samples is achieved by direct conversion of the acetonitrile supernatant of a
      protein precipitation with DMISC followed by a double liquid-liquid extraction
      using n-hexane. Reliability of the method was confirmed under consideration of
      the validation parameters selectivity, linearity, accuracy and precision,
      analytical limits, and processed sample stability. Linearity was demonstrated
      over the whole calibration range from 5 to 1000 ng/ml with the use of a 1/x 2
      weighting. Stability of the processed samples was verified for a time period of
      up to 25 h. Due to its high sensitivity, appropriate quantification and detection
      limits (LLoQ = 5 ng/ml, LoD = 0.95 ng/ml) for toxicological propofol analyses
      could be achieved. Applicability of the method to biological samples could be
      verified by analysis of a human serum sample collected after propofol-induced
      sedation. Graphical abstract A novel derivatization strategy using 1,2
      dimethylimidazole-4-sulfonyl chloride (DMISC) was developed to improve the
      ionization and fragmentation efficacy of propofol for LC-ESI-MS/MS analysis.

PMID- 27873002
TI  - Multimodal detection of GM2 and GM3 lipid species in the brain of
      mucopolysaccharidosis type II mouse by serial imaging mass spectrometry and
      immunohistochemistry.
AB  - Mucopolysaccharidosis type II (Hunter's disease) mouse model (IdS-KO) was
      investigated by both imaging mass spectrometry (IMS) and immunohistochemistry
      (IHC) performed on the same tissue sections. For this purpose, IdS-KO mice brain
      sections were coated with sublimated 1,5-diaminonaphtalene and analyzed by high
      spatial resolution IMS (5 MUm) and anti-GM3 IHC on the same tissue sections to
      characterize the ganglioside monosialated ganglioside (GM) deposits found in
      Hunter's disease. IMS analysis have found that two species of GM3 and GM2 that
      are only different due to the length of their fatty acid residue (stearic or
      arachidic residue) were overexpressed in the IdS-KO mice compared to a control
      mouse. GM3 and GM2 were characterized by on-tissue exact mass and MS/MS compared
      to a GM3 standard. Realignment of both IMS and IHC data sets further confirmed
      the observed regioselective signal previously detected by providing direct
      correlation of the IMS image for the two GM3 overly expressed MS signals with the
      anti-GM3 IHC image. Furthermore, these regioselective GM MS signals were also
      found to have highly heterogeneous distributions within the GM3-IHC staining.
      Some deposits showed high content in GM3 and GM2 stearic species (r = 0.74) and
      others had more abundant GM3 and GM2 arachidic species (r = 0.76). Same-section
      analysis of Hunter's disease mouse model by both high spatial resolution IMS and
      IHC provides a more in-depth analysis of the composition of the GM aggregates
      while providing spatial distribution of the observed molecular species. Graphical
      Abstract Ganglioside imaging mass spectrometry followed by immunohistochemistry
      performed on the same tissue section.

PMID- 27873003
TI  - Localization of ergot alkaloids in sclerotia of Claviceps purpurea by matrix
      assisted laser desorption/ionization mass spectrometry imaging.
AB  - The fungus Claviceps purpurea produces highly toxic ergot alkaloids and
      accumulates these in the hardened bodies of fungal mycelium. These so-called
      sclerotia, or ergot bodies, replace the crop seed of infected plants, which can
      include numerous important food- and feedstuff such as rye and wheat. While
      several studies have explored details of the infection process and development of
      ergot bodies, little information is available on the spatial distribution of the
      mycotoxins in the sclerotia. Here we used matrix-assisted laser
      desorption/ionization mass spectrometry imaging (MALDI-MSI) at a lateral
      resolution of 35 MUm to visualize the distribution of two representative
      alkaloids, ergocristine and ergometrine, produced by Ecc93 and Gal 310 variants
      of C. purpurea, respectively, after infection of rye. To improve cryosectioning
      of this fragile biological material tissue with complex texture, we developed a
      practical embedding protocol based on cellulose polymers. The MALDI-MS images
      recorded from the so produced intact tissues sections revealed that ergometrine
      exhibited a relatively homogeneous distribution throughout the ergot body,
      whereas ergocristine was found to be enriched in the proximal region. This
      finding can be correlated to the morphological development of sclerotia as ergot
      alkaloids are only produced in the sphacelial stage. The ability to localize
      toxins and other secondary metabolites in intact sections of crop-infecting fungi
      with high lateral resolution renders MALDI-MSI a powerful tool for investigating
      biosynthetic pathways and for obtaining a deeper understanding of the parasite
      host interaction. Graphical abstract Workflow for identification and spatial
      localization of ergot alkaloids in infected rye grains.

PMID- 27873004
TI  - Use of a novel metal indicator to judge loop-mediated isothermal amplification
      for detecting the 35S promoter.
AB  - Loop-mediated isothermal amplification (LAMP) is a widely used isothermal nucleic
      acid amplification method. Here we developed a new closed-tube colorimetric
      method for judging LAMP with a novel metal indicator. First, the metal indicator,
      acid chrome blue K (ACBK), was evaluated in the LAMP reaction with various
      combinations of reaction reagents, such as reaction buffer, dNTP mixtures, primer
      mixtures, or Mg2+. We found that the solution color of the LAMP reaction with
      ACBK changed from red to blue based on a decrease in the Mg2+ concentration in
      the reaction solution. We then optimized the LAMP with ACBK method for detecting
      the Cauliflower Mosaic Virus 35S promoter. Further, the specificity of the new
      colorimetric assay using ACBK in the LAMP reaction for detecting the 35S promoter
      was tested with diverse transgenic events in different crops, and the sensitivity
      threshold of the assay was ~50 copies for transgenic rice genomic DNA and 100 ng
      of 0.1 % DNA from rice, soybean, rapeseed, and maize. Finally, the applicability
      of the LAMP assay was successfully validated using practical maize samples. All
      the detection results could be easily discerned either by UV-vis spectroscopy or
      the naked eye. Graphical Abstract The visual detect LAMP amplification by the
      addition of ACBK as a signal indicator. The color of the LAMP-ACBK solution
      turned from red to blue as the concentration of free Mg2+ decreases. The
      detection results could be easily discerned either by UV-vis spectroscopy or the
      naked eye.

PMID- 27873005
TI  - Photoreceptor spectral tuning by colorful, multilayered facet lenses in long
      legged fly eyes (Dolichopodidae).
AB  - The facet lenses of the compound eyes of long-legged flies (Dolichopodidae)
      feature a striking, interlaced coloration pattern, existing of alternating rows
      of green-yellow and orange-red reflecting facets, due to dielectric multilayers
      located distally in the facet lenses (Bernard and Miller. Invest Ophthalmol 7:416
      434 (1968). We investigated this phenomenon in the dolichopodid Dolichopus
      nitidus by applying microspectrophotometry, electron microscopy and optical
      modeling. The measured narrow-band reflectance spectra, peaking at ~540 and ~590
      nm with bandwidth ~105 nm, are well explained by a refractive index oscillating
      sinusoidally in six periods around a mean value of about 1.44 with amplitude 0.6.
      The facet lens reflectance spectra are associated with a spectrally restricted,
      reduced transmittance, which causes modified spectral sensitivities of the
      underlying photoreceptors. Based on the modeling and electroretinography of the
      dolichopodid Condylostylus japonicus we conjecture that the green and orange
      facets narrow the spectral bandwidths of blue and green central photoreceptors,
      respectively, thus possibly improving color and/or polarization vision.

PMID- 27873006
TI  - Feasibility of omitting provocation test with 50 MUg of acetylcholine in left
      coronary artery.
AB  - According to the Japanese Circulation Society guideline of vasospastic angina,
      incremental doses of acetylcholine (ACh) are prescribed for coronary spasm
      provocation: 20 and 50 MUg for the right coronary artery (RCA), and 20, 50 and
      100 MUg for the left coronary artery (LCA). However, provocation by low doses of
      ACh in patients with low vasoreactivity may be less needed, and the requirement
      of 50 MUg of ACh for the LCA in these patients has not been evaluated. In the
      present study, patients who underwent ACh provocation test for both the RCA and
      LCA were included. The positive diagnosis of intracoronary ACh provocation test
      was defined as total or subtotal coronary artery narrowing (i.e., angiographic
      coronary artery spasm) accompanied by chest pain and/or ischemic
      electrocardiographic changes. Coronary artery constriction was visually evaluated
      and defined as coronary artery diameter reduction <25 or 25-90% in patients
      without angiographic coronary artery spasm by 20 ug of ACh in the LCA. There were
      33 out of 249 patients (13%) with LCA spasm by 20 ug of ACh. In subjects without
      LCA spasm by 20 ug of ACh, patients with coronary constriction <25% (n = 101) by
      20 ug of ACh in the LCA rarely showed coronary artery spasm induced by 50 MUg of
      ACh in the LCA, in comparison to those with coronary constriction 25-90% (n =
      115) (2.6 vs. 32.7%, p < 0.001). None of the patients with coronary constriction
      <25% by 20 ug of ACh in the LCA had cardiac complications associated with
      administration of ACh. In conclusion, omission of 50 ug of ACh in the LCA may be
      possible when there is little coronary artery constriction by 20 ug of ACh in the
      LCA during provocation test, leading to less contrast and shortens overall
      procedure time.

PMID- 27873007
TI  - Difference in capsaicinoid biosynthesis gene expression in the pericarp reveals
      elevation of capsaicinoid contents in chili peppers (Capsicum chinense).
AB  - KEY MESSAGE: This research reveals that the up-regulated expression of multiple
      capsaicinoid biosynthetic genes in pericarp tissue leads to the elevation of
      total capsaicinoid content in chili pepper fruit. Capsaicinoids are health
      functional compounds that are produced uniquely in chili pepper fruits. A high
      capsaicinoid level is one of the major parameters determining the commercial
      quality and health-promoting properties of chili peppers. To investigate the
      mechanisms responsible for its high contents, we compared an extremely pungent
      cultivar 'Trinidad Moruga Scorpion Yellow' (MY) with other cultivars of different
      pungency levels (Fushimi-amanaga, Takanotsume, Red Habanero). Capsaicinoid
      concentrations were markedly higher in MY fruit (23.9 mg/g DW) than in other
      pungent cultivars including 'Red Habanero' (HB) fruit (14.3 mg/g DW). Comparative
      analysis of MY and HB reveals that both cultivars accumulated similar
      capsaicinoid concentrations in the placental septum, with that in the HB pericarp
      (1.8 mg/g DW) being markedly lower than that in the placental septum (69.1 mg/g
      DW). The capsaicinoid concentration in HB fruit is dependent on the placental
      septum, as reported in other accessions. Therefore, even though placental septum
      tissue contains high capsaicinoid concentrations, those in the pericarp and seeds
      attenuated its total content. In contrast, the MY pericarp exhibited a markedly
      higher concentration (23.2 mg/g DW). A qRT-PCR analysis revealed that multiple
      capsaicinoid biosynthetic pathway genes (Pun1, pAMT, KAS, and BCAT) were strongly
      up-regulated in placental septum of pungent cultivars. The genes were expressed
      exclusively in the MY pericarp, but were barely detected in the pericarps of
      other pungent cultivars. Collectively, the present study indicates that the up
      regulated expression of these genes not only in placental septum but also in
      pericarp plays an important role in driving capsaicinoid accumulation in the
      whole fruit.

PMID- 27873008
TI  - Arterial stiffness and peripheral arterial disease in patients with systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is associated with increased cardiovascular
      risk. We aimed to evaluate arterial stiffness and the ankle brachial index (ABI),
      two markers of subclinical cardiovascular disease, in SLE. We studied 55 patients
      with SLE (12.7% males, age 53.3 +/- 15.3 years) and 61 age- and gender-matched
      controls. Arterial stiffness was evaluated by measuring pulse wave velocity
      (PWV), augmentation index (AIx) and central systolic, diastolic, pulse and mean
      blood pressure (BP). Peripheral arterial disease was defined as ABI <= 0.90.
      Regarding markers of arterial stiffness, patients with SLE had lower PWV and AIx
      than controls (p < 0.01 and p < 0.05, respectively). However, after adjusting for
      differences in cardiovascular risk factors between patients with SLE and
      controls, PWV and AIx did not differ between the two groups. Central systolic,
      diastolic, pulse and mean BP also did not differ between the two groups. In
      patients with SLE, PWV correlated independently with systolic BP (B = 0.05, p <
      0.001) and waist/hip ratio (B = 6.72, p < 0.05). Regarding ABI, the lowest ABI
      was lower in patients with SLE than in controls (p < 0.005). However, after
      adjusting for differences in cardiovascular risk factors between patients with
      SLE and controls, the lowest ABI did not differ between the two groups. The
      prevalence of PAD also did not differ between patients with SLE and controls
      (10.0 and 5.4%, respectively; p = NS). Markers of arterial stiffness and the ABI
      do not appear to differ between patients with SLE and age- and gender-matched
      controls. However, given the small sample size, larger studies are needed to
      clarify whether SLE promotes arterial stiffness and PAD.

PMID- 27873010
TI  - Regional block via continuous caudal infusion as sole anesthetic for inguinal
      hernia repair in conscious neonates.
AB  - PURPOSE: The use of general anesthesia in young children has come under
      increasing scrutiny due to its potential long-term neurotoxic effects. Meanwhile,
      regional anesthesia for surgical procedures in neonates has many advantages,
      including preservation of respiratory status and faster return to feeding. We
      describe the successful use of 3% 2-chloroprocaine administered via continuous
      caudal infusion as the sole anesthetic agent during elective surgical procedures
      in infants. METHODS: A retrospective chart review of all patients who underwent
      elective surgical procedures under continuous caudal regional anesthetic at a
      single institution was performed. Thirty patients (27 males, three females) were
      identified: 28 patients underwent inguinal hernia repairs. Caudal anesthesia was
      established via continuous infusion of 3% 2-chloroprocaine through an indwelling
      catheter. RESULTS: Successful analgesia by regional block alone was achieved in
      all patients for the duration of each surgical procedure without need for rescue
      anesthesia. Mean operative time was 49 min. Patients were able to return to
      feeding immediately after surgery and were ready for discharge home within that
      day. CONCLUSION: Continuous caudal infusion of chloroprocaine is a safe and
      effective way to maintain adequate analgesia for elective surgeries in infants.
      This successful regional approach obviates the use of general anesthetic which
      reduces post-operative recovery time and avoids concerns for neurotoxicity.

PMID- 27873011
TI  - Laparoscopic resection of choledochal cyst with Roux-en-Y hepaticojejunostomy: a
      case report and review of the literature.
AB  - BACKGROUND: Choledochal cysts are associated with ductal strictures, stone
      formation, cholangitis, rupture, secondary biliary cirrhosis and increased
      incidence of cholangiocarcinoma. The surgical approach to choledochal cysts has
      evolved from the cyst-enterostomy to a complete excision with more recent use of
      minimally invasive approaches. We report a complete minimally invasive approach
      to a Type 1 choledochal cyst and summarize the literature containing large case
      series of similar approaches. METHODS AND OPERATIVE TECHNIQUE: A 38-year-old
      female with a history of vague epigastric pain for multiple years was diagnosed
      with a Type 1 choledochal cyst on MRCP. The operative approach was an elective
      laparoscopic resection of choledochal cyst and Roux-en-Y hepaticojejunostomy.
      There were no intraoperative complications and discharge occurred on
      postoperative day three. Approximately 1 month after resection, she was diagnosed
      with a small retrohepatic fluid collection which was treated percutaneously and
      was diagnosed as a hematoma. A PubMed literature review focusing on surgical
      approaches to Type 1 choledochal cysts methods of repair and postoperative
      complications was performed and summarized. RESULTS AND DISCUSSION: The
      literature search performed on the subject of choledochal cyst management in
      adults and laparoscopic approaches resulted in a review of twenty-one articles.
      Ten of the articles were review articles regarding surgical approach and
      management of the disease. An additional two were case reviews, and eight
      reported on laparoscopic approaches to management of choledochal cysts. In this
      paper, we summarize the eight articles that provide information on the
      laparoscopic management and outcomes for choledochal cysts. While operative times
      were longer on the laparoscopic procedures, hospital stay was shorter and there
      was no increase in complication rates. The most common complications reported
      were postoperative bile leak followed by anastomotic stricture. CONCLUSION: This
      case highlights the management of laparoscopic resection of choledochal cyst as a
      viable, safe and feasible approach based on this case and a literature review.

PMID- 27873009
TI  - Systematic review and need assessment of pediatric trauma outcome benchmarking
      tools for low-resource settings.
AB  - INTRODUCTION: Trauma is a leading cause of mortality and disability in children
      worldwide. The World Health Organization reports that 95% of all childhood injury
      deaths occur in Low-Middle-Income Countries (LMIC). Injury scores have been
      developed to facilitate risk stratification, clinical decision making, and
      research. Trauma registries in LMIC depend on adapted trauma scores that do not
      rely on investigations that require unavailable material or human resources. We
      sought to review and assess the existing trauma scores used in pediatric
      patients. Our objective is to determine their wideness of use, validity, setting
      of use, outcome measures, and criticisms. We believe that there is a need for an
      adapted trauma score developed specifically for pediatric patients in low
      resource settings. MATERIALS AND METHODS: A systematic review of the literature
      was conducted to identify and compare existing injury scores used in pediatric
      patients. We constructed a search strategy in collaboration with a senior
      hospital librarian. Multiple databases were searched, including Embase, Medline,
      and the Cochrane Central Register of Controlled Trials. Articles were selected
      based on predefined inclusion criteria by two reviewers and underwent qualitative
      analysis. RESULTS: The scores identified are suboptimal for use in pediatric
      patients in low-resource settings due to various factors, including reliance on
      precise anatomic diagnosis, physiologic parameters maladapted to pediatric
      patients, or laboratory data with inconsistent accessibility in LMIC. CONCLUSION:
      An important gap exists in our ability to simply and reliably estimate injury
      severity in pediatric patients and predict their associated probability of
      outcomes in settings, where resources are limited. An ideal score should be easy
      to calculate using point-of-care data that are readily available in LMIC, and can
      be easily adapted to the specific physiologic variations of different age groups.

PMID- 27873012
TI  - Robotic cholecystectomy using Revo-i Model MSR-5000, the newly developed Korean
      robotic surgical system: a preclinical study.
AB  - BACKGROUND: Laparoscopic surgery has become the standard option for
      gastrointestinal surgeries. However, laparoscopic procedures require extended
      training times and are difficult for inexperienced surgeons. Robot-assisted
      laparoscopic surgery facilitates easy adaptation of laparoscopic procedures, but
      robotic surgical systems are expensive. In addition, their cost has remained high
      because there is currently only one manufacturer of commercially available
      systems. Recently, a new Korean robotic surgical system, Revo-i, has been
      developed. The aim of this study was to evaluate the feasibility and safety of
      Revo-i by performing robotic cholecystectomy in a porcine model. METHODS: After
      approval by the Institutional Animal Care and Use Committee of Yonsei University
      Health System, cholecystectomy was performed in four pigs using the Revo-i
      robotic surgical system. Operative time and perioperative complications were
      recorded, and all animals were observed for postoperative complications for 2
      weeks after surgery RESULTS: Robotic cholecystectomy was completed successfully
      and without gallbladder perforation in all cases. The mean operative time was 78
      +/- 12 min, the mean docking time was 4.5 +/- 2.52 min, and the mean console time
      was 49.8 +/- 14.17 min. There were no perioperative complications, and none of
      the animal used for the in vivo models exhibited abnormal behavior during the
      postoperative observation period. CONCLUSIONS: These preliminary results verify
      the safety and efficacy of robotic cholecystectomy using the Revo-i robotic
      surgical system. Human trials are slated to begin accordingly.

PMID- 27873013
TI  - Neonatal L-glutamine modulates anxiety-like behavior, cortical spreading
      depression, and microglial immunoreactivity: analysis in developing rats suckled
      on normal size- and large size litters.
AB  - In mammals, L-glutamine (Gln) can alter the glutamate-Gln cycle and consequently
      brain excitability. Here, we investigated in developing rats the effect of
      treatment with different doses of Gln on anxiety-like behavior, cortical
      spreading depression (CSD), and microglial activation expressed as Iba1
      immunoreactivity. Wistar rats were suckled in litters with 9 and 15 pups (groups
      L 9 and L 15; respectively, normal size- and large size litters). From postnatal
      days (P) 7-27, the animals received Gln per gavage (250, 500 or 750 mg/kg/day),
      or vehicle (water), or no treatment (naive). At P28 and P30, we tested the
      animals, respectively, in the elevated plus maze and open field. At P30-35, we
      measured CSD parameters (velocity of propagation, amplitude, and duration).
      Fixative-perfused brains were processed for microglial immunolabeling with anti
      IBA-1 antibodies to analyze cortical microglia. Rats treated with Gln presented
      an anxiolytic behavior and accelerated CSD propagation when compared to the water
      and naive control groups. Furthermore, CSD velocity was higher (p < 0.001) in
      the L 15 compared to the L 9 condition. Gln treatment increased Iba1
      immunolabeling both in the parietal cortex and CA1 hippocampus, indicating
      microglial activation. The Gln effect was dose-dependent for anxiety-like
      behavior and CSD in both litter sizes, and for microglial activation in the L 15
      groups. Besides confirming previous electrophysiological findings (CSD
      acceleration after Gln), our data demonstrate for the first time a behavioral and
      microglial activation that is associated with early Gln treatment in developing
      animals, and that is possibly operated via changes in brain excitability.

PMID- 27873014
TI  - Binocular function changes produced in response to overnight orthokeratology.
AB  - PURPOSE: To analyze the binocular function changes produced on subjects
      undergoing overnight orthokeratology (OK) treatment over short-term (3 months)
      and long-term (3 years) wear. METHODS: A prospective, longitudinal study on young
      adult subjects with low to moderate myopia was carried out. Binocular function
      was assessed by the following sequence of tests: Distance and near horizontal
      phoria (Von Graefe technique), distance and near horizontal vergence ranges
      (Risley rotary prisms), accommodative convergence/accommodation (AC/A) ratio
      (gradient method) and the near point of convergence (standard push-up technique).
      The short-term sample consisted of: 21 subjects in the control group, 26 in a
      corneal refractive therapy (CRT) treatment lenses group and 25 in a Seefree
      treatment lenses group. Those subjects were evaluated at baseline and at a 3
      month follow-up visit. Twenty one subjects were old CRT wearers that attended a 3
      year follow-up visit (long-term group). RESULTS: A statistically significant
      difference over the 3-month treatment was found for divergence at distance: the
      break point decreased 1.4 Delta (p = 0.0006) in the CRT group and the recovery
      point increased 1.2 Delta (p = 0.001) in the Seefree group. Also, the Seefree
      group had an exophoric trend of 2.3 Delta at near (p = 0.02) and a base-out break
      decrease of 2.3 Delta (p = 0.03). For the long-term group, only the base-out
      break point at distant vision showed a statistically significant difference of
      4.9 Delta (p = 0.02). CONCLUSIONS: OK induces minimal changes in the binocular
      function for either short-term or long-term periods, apart from a near exophoric
      trend over the short-term period.

PMID- 27873015
TI  - Muscarinic receptor binding changes in postmortem Parkinson's disease.
AB  - Parkinson's disease (PD) is a devastating disorder, affecting approximately 2% of
      people aged 60 and above. It is marked by progressive neurodegeneration that has
      long been known to impact dopaminergic cells and circuits, but more recently the
      acetylcholine system has also been implicated in the complex aetiology and
      symptomatology of the disease. While broad changes in cholinergic markers have
      been described, insight into the contribution of specific acetylcholine receptors
      is less clear. To address this important unknown, in this study we performed [3H]
      pirenzepine, [3H] 4DAMP, and [3H] AF-DX 384 in situ radioligand binding on
      postmortem tissues from Brodmann's area 6, 9, 46, and the caudate putamen, from
      PD and matched controls to detect muscarinic M1, M3, and M1/2/4 receptors,
      respectively. We found no difference in [3H] pirenzepine binding between PD and
      controls across all regions assessed. [3H] 4DAMP binding was found to be higher
      in PD CPu and BA9 than in controls. [3H] AF-DX 384 was higher in BA9 of PD
      compared with controls. In sum, we show selective increase in M3 receptors in
      cortical and subcortical regions, as well as increased M2/M4 in cortical area
      BA9, which together support a role for cholinergic dysfunction in PD.

PMID- 27873017
TI  - Erratum to: No evidence for shared representations of task sets in joint task
      switching.

PMID- 27873016
TI  - Return to work among breast cancer survivors: A literature review.
AB  - PURPOSE: Breast cancer survivors in their employment years are likely to try to
      go back to work after the primary treatment. Because the literature on return to
      work among breast cancer survivors is limited, we have undertaken a review of the
      literature to summarize what is known, including identifying important
      contributing variables and outcomes. This knowledge may be used to develop
      hypotheses and potential interventions to support breast cancer survivors who
      wish to return to work. METHOD: We searched the following databases: CINAHL,
      MEDLINE, SCOUP, and PUBMED, within a 10-year timeframe (2004 to 2014). RESULTS:
      The majority of reviewed articles (N = 25) focused on three outcomes: return-to
      work period, work ability, and work performance. The most frequently studied
      independent variables were collapsed into the following groups: health and well
      being, symptoms and functioning, work demands and work environment, individual
      characteristics, and societal and cultural factors. Gaps in the literature
      include evidence of effective interventions to support return to work among
      breast cancer survivors and research to better understand the roles of government
      and business-related policy. CONCLUSION: All the studies reported a reduced work
      engagement and work ability. Employment status and work performance is associated
      with a combination of individual factors, work environment, culture, and
      resources. IMPLICATIONS: Significant gaps are apparent in the literature
      addressing breast cancer survivorship and return to work. This is a complex
      problem and it will likely require interdisciplinary research teams to develop
      effective and feasible interventions for this population.

PMID- 27873019
TI  - Arterial stiffness in young adult swimmers.
AB  - PURPOSE: Habitual Aerobic exercise reduces arterial stiffness, but effects of
      habitual swimming on arterial stiffness are not yet fully understood. Swimming
      can also increase systolic blood pressure (BP) in normotensive individuals.
      Accordingly, this cross-sectional study aimed to investigate arterial stiffness
      in young adult swimmers after considering the influence of BP. METHODS:
      Participants comprised 41 men (18-21 years), including 15 untrained controls (C),
      11 competitive cyclists (aerobic-trained athletes; A), and 15 competitive
      swimmers (S). Arterial stiffness was assessed by brachial-ankle pulse-wave
      velocity (baPWV), heart-ankle pulse-wave velocity (haPWV), and cardio-ankle
      vascular index (CAVI). CAVI is the measurement of arterial stiffness that is
      theoretically adjusted by BP. RESULTS: Although physical characteristics and
      handgrip strength did not differ between groups, peak oxygen uptake was
      significantly greater in A and S than in C. A tendency towards higher systolic BP
      and a significantly higher pulse pressure were found in S as compared to C and A.
      Most importantly, baPWV was significantly lower in A than in C or S, and no
      significant difference in baPWV was observed between C and S (C, 1027 +/- 25; A,
      852 +/- 23; S, 1032 +/- 24 cm/s). No significant difference in haPWV was
      observed. However, CAVI was significantly lower in A and S than in C, and did not
      differ significantly between A and S (C, 5.8 +/- 0.2; A, 5.1 +/- 0.2; S, 5.3 +/-
      0.2 unit). CONCLUSION: These findings indicate that arterial stiffness in young
      adult swimmers is lower than in age-matched sedentary controls and similar to
      land-based aerobic-exercise individuals, after considering the influences of BP.

PMID- 27873021
TI  - ?

PMID- 27873018
TI  - Soft tissue augmentation around osseointegrated and uncovered dental implants: a
      systematic review.
AB  - OBJECTIVES: The aim was to compile the current knowledge about the efficacy of
      different soft tissue correction methods around osseointegrated, already
      uncovered and/or loaded (OU/L) implants with insufficient soft tissue conditions.
      Procedures to increase peri-implant keratinized mucosa (KM) width and/or soft
      tissue volume were considered. MATERIALS AND METHODS: Screening of two databases:
      MEDLINE (PubMed) and EMBASE (OVID), and manual search of articles were performed.
      Human studies reporting on soft tissue augmentation/correction methods around
      OU/L implants up to June 30, 2016, were considered. Quality assessment of
      selected full-text articles to weight risk of bias was performed using the
      Cochrane collaboration's tool. RESULTS: Overall, four randomized controlled
      trials (risk of bias = high/low) and five prospective studies (risk of bias =
      high) were included. Depending on the surgical techniques and graft materials,
      the enlargement of keratinized tissue (KT) ranged between 1.15 +/- 0.81 and 2.57
      +/- 0.50 mm. The apically positioned partial thickness flap (APPTF), in
      combination with a free gingival graft (FGG), a subepithelial connective tissue
      graft (SCTG), or a xenogeneic graft material (XCM) were most effective. A
      coronally advanced flap (CAF) combined with SCTG in three, combined with
      allogenic graft materials (AMDA) in one, and a split thickness flap (STF)
      combined with SCTG in another study showed mean soft tissue recession coverage
      rates from 28 to 96.3 %. STF combined with XCM failed to improve peri-implant
      soft tissue coverage. CONCLUSIONS: The three APPTF-techniques combined with FGG,
      SCTG, or XCM achieved comparable enlargements of peri-implant KT. Further, both
      STF and CAF, both in combination with SCTG, are equivalent regarding recession
      coverage rates. STF + XCM and CAF + AMDA did not reach significant coverage.
      CLINICAL RELEVANCE: In case of soft tissue deficiency around OU/L dental
      implants, the selection of both an appropriate surgical technique and a suitable
      soft tissue graft material is of utmost clinical relevance.

PMID- 27873020
TI  - Beneficial and limiting factors for return to work following anterior cruciate
      ligament reconstruction: a retrospective cohort study.
AB  - PURPOSE: Evidence-based advice for return to work (RTW) after anterior cruciate
      ligament (ACL) reconstruction is not available. Therefore, the objectives of this
      study were to determine when patients achieve full RTW, and to explore the
      beneficial and limiting factors for fully RTW after ACL reconstruction. METHODS:
      A retrospective cohort study was performed after ACL reconstruction among 185
      patients in one hospital. Data from patient files and a questionnaire were used
      to explore whether patient-, injury-, surgery-, sports-, work- and rehabilitation
      related factors are beneficial or limiting for fully RTW after ACL
      reconstruction, using a backward stepwise logistic regression analysis. RESULTS:
      Of the 125 (68%) patients that returned the questionnaire, 36 were not part of
      the working population. Of the remaining 89 patients, 82 patients (92%) had
      returned fully to work at follow-up. The median time to fully RTW was 78 days. In
      the final regression model, which explained 29% of the variance, a significant OR
      of 5.4 (90% CI 2.2-13.1) for RTW > 78 days was observed for patients performing
      heavy knee-demanding work compared to patients performing light knee-demanding
      work. In addition, a significant and positive OR (1.6, 90% CI 1.2-1.9) for the
      number of weeks walking with the aid of crutches for RTW > 78 days was observed
      in the final model. CONCLUSION: After ACL reconstruction, 92% of the patients
      fully return to work at a median time of 78 days. The significant predictors for
      fully RTW > 78 days are performing heavy knee-demanding work and a longer period
      of walking aided with crutches after ACL reconstruction.

PMID- 27873022
TI  - Current rare indications and future directions for implantable loop recorders.
AB  - The scope of application for implantable loop recorders has shifted away from the
      evaluation of unclear palpitations and syncope episodes to more complex
      conditions. This article focuses on rare indications of growing importance such
      as rhythm monitoring after ablation of atrial fibrillation or after cryptogenic
      stroke. Furthermore, forthcoming applications in various clinical settings are
      described, e. g., arrhythmia detection after myocardial infarction, after
      catheter-based valve interventions, in heart failure, and in cardiomyopathies.
      Enhancement of the capabilities of implantable loop recorders could broaden their
      fields of use.

PMID- 27873024
TI  - P4 medicine and osteoporosis: a systematic review.
AB  - BACKGROUND: Osteoporosis is the most frequent bone metabolic disease. In order to
      improve early detection, prediction, prevention, diagnosis, and treatment of the
      disease, a new model of P4 medicine (personalized, predictive, preventive, and
      participatory medicine) could be applied. The aim of this work was to
      systematically review the publications of four different types of "omics" studies
      related to osteoporosis, in order to discover novel predictive, preventive,
      diagnostic, and therapeutic targets for better management of the geriatric
      population. METHODS: To systematically search the PubMed database, we created
      specific groups of criteria for four different types of "omics" information on
      osteoporosis: genomic, transcriptomic, proteomic, and metabolomic. We then
      analyzed the intersections between them in order to find correlations and common
      pathways or molecules with important roles in osteoporosis, and with a potential
      application in disease prediction, prevention, diagnosis, or treatment. RESULTS:
      Altogether, 180 publications of "omics" studies in the field of osteoporosis were
      found and reviewed at first selection. After introducing the inclusion and
      exclusion criteria (the secondary selection), 46 papers were included in the
      systematic review. CONCLUSIONS: The intersection of reviewed papers identified
      five genes (ESR1, IBSP, CTNNB1, SOX4, and IDUA) and processes like the Wnt
      pathway, JAK/STAT signaling, and ERK/MAPK, which should be further validated for
      their predictive, diagnostic, or other clinical value in osteoporosis. Such
      molecular insights will enable us to fit osteoporosis into the P4 strategy and
      could increase the effectiveness of disease prediction and prevention, with a
      decrease in morbidity in the geriatric population.

PMID- 27873023
TI  - Therapeutic efficacy of azithromycin and acetylcysteine in chronic otitis media
      with effusion.
AB  - Otitis media with effusion (OME) is a common disease in childhood. There is no
      consensus on the optimal therapeutic option for OME. Considering the known
      efficacy of acetylcysteine (AC) and azithromycin (AZ) in the treatment of middle
      ear mucosa, the aim of the study was to assess their efficacy in the management
      of chronic OME. The study included 90 children with OME, both ears. They are
      divided into three groups of 30 children. Group 1 (AC) patients were treated with
      acetylcysteine per os, 3 * 100 mg, for 3 weeks; group 2 (AZ) with body weight
      adjusted dose of azithromycin for 3 days; and group 3 (AC + AZ) with a
      combination of acetylcysteine and azithromycin at doses described above. Three
      measurements were performed. On second measurement, tympanogram improvement was
      recorded in 45% of 60 ears in group I, 53.3% of 60 ears in group II, and 61.7% of
      60 ears in group III. The percentage of improvement was highest in group III.
      Although between-group differences did not reach statistical significance, the
      results obtained appear to be clinically relevant. In conclusion, conservative
      therapy for chronic OME is reasonable. Although study results don't have a strong
      statistical differences and may not refer clinical improvement results suggest
      that this combination of drugs (antibiotics, bronchosecretolytics) can be useful
      in the treatment of OME.

PMID- 27873025
TI  - The relativity of age or geriatric medicine at the crossroads.

PMID- 27873026
TI  - Long-term efficacy and side effects of low-dose tacrolimus for the treatment of
      Myasthenia Gravis.
AB  - The study evaluated the efficacy of low-dose tacrolimus for treating Myasthenia
      Gravis (MG). Data were collected from 97 patients treated with low-dose
      tacrolimus from February 2011 to April 2015. Metabolic analysis was performed to
      determine more accurate tacrolimus dosing and patients were followed-up within
      clinic every 6 months for up to 4 years. The myasthenia gravis-specific
      activities of daily living scale was used to assess MG symptoms and their effects
      on patients' daily activities. All side effects and adverse reactions were
      thoroughly documented. At the end of follow-up, 6 patients were in complete
      stable remission, 17 patients were in pharmacological remission, 26 patients were
      in minimal manifestation status, 32 patients were improved, 2 patients were
      unchanged, 11 patients had worsening symptoms, and 3 patients died. Side effects
      were reported and/or observed in 24 patients, of which 7 patients experienced
      elevated blood glucose, 2 patients developed neoplasms, 3 patients developed
      gastrointestinal symptoms, 3 showed mild increases in aminotransferases, 3
      patients suffered from bone marrow suppression, 2 patients suffered from skin
      rashes and erythema, and 1 patient required discontinuation of therapy. Transient
      renal insufficiency was also observed in 1 patient and 3 other patients had minor
      miscellaneous side effects. This study adds some knowledge on the efficacy and
      side effects of low-dose tacrolimus in the treatment of MG. Tacrolimus
      immunotherapy is a valid option for the management of MG, and can be gradually
      reduced in dose once symptoms are improved until complete withdrawal is achieved.

PMID- 27873027
TI  - Assessing Clinical Improvement in School-Based Treatment for Social Anxiety
      Disorder: Agreement Between Adolescents, Parents, and Independent Evaluators.
AB  - The Clinical Global Impressions of Improvement (CGI-I) scale is widely used in
      clinical trials to monitor clinically meaningful change during treatment.
      Although it is standard practice in research to have independent evaluators (IEs)
      complete the CGI-I, this approach is not practical in school and community
      settings. Few studies have explored the potential utility of other informants,
      such as youth and parents. Therefore, this study aimed to investigate agreement
      between IEs and both adolescents and parents in CGI-I improvement ratings in the
      context of a randomized controlled trial of cognitive-behavioral therapy for
      social anxiety disorder, as delivered by psychologists and school counselors.
      Multilevel growth models indicated that IEs were generally more conservative in
      their ratings of positive treatment response across time and treatment
      conditions, though greater agreement was observed between parents and IEs by post
      intervention and 5-month follow-up. Possible explanations for these findings and
      suggestions for alternative approaches are discussed.

PMID- 27873029
TI  - Induction of pluripotency in long-term cryopreserved human neonatal fibroblasts
      in feeder-free condition.
AB  - A novel approach for stem cell generation is the attempt to induce conversion of
      the adult somatic cells into pluripotent stem cells so called induced pluripotent
      stem cells (iPSCs) by introducing specific transcription factors. iPSCs have two
      essential cell characteristics, they are pluripotent and posses long term cell
      renewal capacity. Additionally, iPSCs can be derived from patient-specific
      somatic cells, thus bypassing ethical and immunological issues. The aim of our
      study was to reprogram long-term cryopreserved human neonatal fibroblasts by new
      method using lipid nano-particle technology (Lipofectamine 3000 reagent
      transfection system) in combination with Epi 5 reprogramming vectors. Obtained
      iPSCs were characterized by several sophisticated methods of molecular biology
      and microscopy. Distinct colonies of iPSCs started to appear by day 20 after
      reprogramming. The presence of iPSCs colonies was proved by alkaline phosphatase
      (AP) live staining. After manual picking the colonies and their subsequent
      passaging, they did not lose ability to form embryoid bodies, they were positive
      for AP, Tra-1-60, and SSEA-5. Moreover, obtained iPSCs expressed pluripotency
      markers Oct4, Sox2 and Nanog, and the expression levels of chondrogenic,
      osteogenic and adipogenic markers were significantly higher in comparison to
      control (p < 0.05). In summary, we have demonstrated that long-term cryopreserved
      human neonatal fibroblasts can be reprogrammed into iPSCs and after further
      analysis concerns on their biological safety they may be used as patient-specific
      cells in regenerative medicine.

PMID- 27873030
TI  - Chloroplast DNA sequencing and detailed microsatellite genotyping of all remnant
      populations suggests that only a single genet survives of the critically
      endangered plant Rehmannia japonica.
AB  - Rehmannia japonica (Thunb.) Makino ex T. Yamaz. is an endangered perennial herb
      species in Japan. Although earlier the Japanese considered it a variety of R.
      glutinosa, recent Japanese taxonomists have consistently regarded it as an
      independent species. According to the historical literature, Rehmannia japonica
      seems to have been known in China and Japan in the past. However, Chinese
      taxonomists do not recognize R. japonica at present. In Japan, only two
      populations are known, and although these populations flower every year, seed
      reproduction has not been observed. In this study, we aimed to reveal the
      phylogenetic relationships and levels of genetic diversity of R. japonica. A
      haplotype network based on two chloroplast DNA regions (trnL-trnF and rps16)
      showed that the sequences of R. japonica were distinguishable by three or four
      sites of indels from the most closely related species, R. chingii, consistent
      with the separate species status of R. japonica. An analysis of genetic diversity
      using twelve microsatellite loci showed that all of the ramets of R. japonica
      collected from two geographically isolated populations had an identical
      multilocus genotype, including identical heterozygous genotypes at six loci. This
      result indicated asexual origin of all sampled ramets. This study also suggests
      that the absence of sexual reproduction of R. japonica is explained by self
      incompatibility combined with only a single genet remaining in the R. japonica
      populations.

PMID- 27873028
TI  - MCR: modern colistin resistance.
AB  - Recently, plasmid-mediated and, therefore, transferable bacterial polymyxin
      resistance was discovered in strains from both humans and animals. Such a trait
      may widely spread geographically, while simultaneously crossing microbial species
      barriers. This may ultimately render the "last resort" polymyxin antibiotics
      therapeutically useless. Colistin is currently used to treat infections caused by
      Gram-negative carbapenemase producers and colistin resistance may lead to
      practical pan-antibiotic resistance. We here analyzed the medical and diagnostic
      consequences of (emerging) colistin resistance and propose pathways toward
      adequate diagnostics for timely detection of both asymptomatic carriage and
      infection. Culture-based testing using chromogenic and selective media for
      screening clinical (and veterinary) specimens may constitute key tools for that
      purpose. Relevant molecular tests are also discussed.

PMID- 27873031
TI  - Stability of Sexual Attractions Across Different Timescales: The Roles of
      Bisexuality and Gender.
AB  - We examined the stability of same-sex and other-sex attractions among 294
      heterosexual, lesbian, gay, and bisexual men and women between the ages of 18 and
      40 years. Participants used online daily diaries to report the intensity of each
      day's strongest same-sex and other-sex attraction, and they also reported on
      changes they recalled experiencing in their attractions since adolescence. We
      used multilevel dynamical systems models to examine individual differences in the
      stability of daily attractions (stability, in these models, denotes the tendency
      for attractions to "self-correct" toward a person-specific setpoint over time).
      Women's attractions showed less day-to-day stability than men's, consistent with
      the notion of female sexual fluidity (i.e., heightened erotic sensitivity to
      situational and contextual influences). Yet, women did not recollect larger post
      adolescent changes in sexual attractions than did men, and larger recollected
      post-adolescent changes did not predict lower day-to-day stability in the sample
      as a whole. Bisexually attracted individuals recollected larger post-adolescent
      changes in their attractions, and they showed lower day-to-day stability in
      attractions to their "less-preferred" gender, compared to individuals with
      exclusive same-sex or exclusive other-sex attractions. Our results suggest that
      both gender and bisexuality have independent influences on sexual fluidity, but
      these influences vary across short versus long timescales, and they also differ
      for attractions to one's "more-preferred" versus "less-preferred" gender.

PMID- 27873032
TI  - Linking Crime to Paraphilia: Be Careful with Label.

PMID- 27873033
TI  - Stability of Bisexual Behavior and Extent of Viral Bridging Behavior Among Men
      Who Have Sex with Men and Women.
AB  - Bisexual men experience significant health disparities likely related to
      biphobia. Biphobia presents via several preconceptions, including that
      bisexuality is transitory, and that bisexual men act as viral bridges between men
      who have sex with men and heterosexual populations. We analyzed data from a
      prospective cohort of gay and bisexual men, the Multicenter AIDS Cohort Study, to
      test these preconceptions. Men reporting both male and female sexual partners
      (MSMW) between 2002 and 2009 (n = 111) were classified as behaviorally bisexual.
      We assessed five hypotheses over two domains (transience of bisexual behavior and
      viral bridging). No evidence was found supporting the transitory nature of
      bisexuality. Trajectories of bisexual behavior were not transient over time. We
      found little evidence to support substantial viral bridging behavior. Notably,
      HIV-positive MSMW reported lower proportions of female partners than HIV-negative
      MSMW. Our results provide no empirical support for bisexual transience and scant
      support for viral bridging hypotheses. Our results provide key data showing that
      male bisexual behavior may be stable over long time periods and that behaviorally
      bisexual men's risk to female sexual partners may be lower than expected.

PMID- 27873036
TI  - List of referees.

PMID- 27873035
TI  - DMFC (3,5-dimethyl-7H-furo[3,2-g]chromen-7-one) regulates Bim to trigger Bax and
      Bak activation to suppress drug-resistant human hepatoma.
AB  - 3,5-Dimethyl-7H-furo[3,2-g]chromen-7-one (DMFC) is a coumarin derivative with
      anti-cancer activity against human hepatoma cells, but the mechanisms underlying
      DMFC function in cancer suppression is unknown. In this study, we aimed at
      elucidating the molecular mechanisms underlying DMFC anti-cancer activity and
      determining whether DMFC is effective in suppression of drug-resistant human
      hepatocellular carcinoma. We show here that DMFC effectively suppresses both the
      parent and the multidrug-resistant hepatoma cell growth in vitro and DMFC
      suppresses hepatoma cell growth at least in part through inducing tumor cell
      apoptosis. In the molecular level, we observed that DMFC treatment decreases Bcl
      2 level by a post-transcriptional mechanism and activates Bim transcription to
      increase Bim mRNA and protein level in hepatoma cells. Furthermore, co
      immunoprecipitation studies revealed that DMFC-induced Bim interrupts
      interactions between Bcl-2 and Bax and between Mcl-1 and Bak, resulting in
      dissociation of Bax from Bcl-2 and Bak from Mcl-1 and subsequent activation of
      both Bax and Bak. Activation of Bax and Bak leads to mitochondrial outer membrane
      permeabilization and cytochrome c release. Consistent with its potent apoptosis
      inducing activity, DMFC exhibited potent activity against the multidrug-resistant
      hepatoma xenograft growth in vivo. Therefore, we determine that DMFC suppresses
      hepatoma growth through decreasing Bcl-2 and increasing Bim to induce tumor cell
      apoptosis and hold great promise for further development as a therapeutic agent
      to treat chemoresistant hepatoma.

PMID- 27873037
TI  - The true distribution volume and bioavailability of mizoribine in children with
      chronic kidney disease.
AB  - BACKGROUND: Mizoribine (MZR) is used kidney transplant and various kidney
      diseases. However, few studies reported the association between pharmacokinetics
      and pharmacodynamics. The Pharmacokinetics Study Group for Pediatric Kidney
      Disease (PSPKD) used population pharmacokinetics (PPK) analysis and Bayesian
      analysis to investigate the usefulness of MZR. In this study, the fact that
      almost all MZR are excreted unchanged in urine was used to calculate its
      bioavailability (F) and true distribution volume (V d), and analyzed these
      correlation with age. METHODS: Ishida et al. reported a PPK analysis by the
      PSPKD. In the present study, 71 samples extracted from their study population of
      105 pediatric chronic kidney disease patients aged between 1 and 20 years were
      investigated. The bioavailability was calculated by measuring total excreted MZR
      in 24 h urine samples, and this was compared to the oral dosage. The apparent
      distribution volume (V d/F) obtained from Bayesian analysis was then used to
      calculate true distribution volume (V d), and the correlation of each parameter
      with age was investigated. RESULTS: The median dose of MZR per weight was 5.17
      mg/kg/day. Median bioavailability was 32.02%. Median V d per weight was 0.46
      L/kg. There was a significant, weakly positive correlation between
      bioavailability and age (p = 0.026). There was also a significant, weakly
      negative correlation between V d per weight and age (p = 0.003). CONCLUSION:
      Bioavailability and V d per weight tended to decrease depending on age. The
      younger patient required larger dose required to obtain the maximum effect from
      MZR, and this is important for immunosuppressive therapy.

PMID- 27873034
TI  - On the Mechanics of Transcatheter Aortic Valve Replacement.
AB  - Transcatheter aortic valves (TAVs) represent the latest advances in prosthetic
      heart valve technology. TAVs are truly transformational as they bring the benefit
      of heart valve replacement to patients that would otherwise not be operated on.
      Nevertheless, like any new device technology, the high expectations are dampened
      with growing concerns arising from frequent complications that develop in
      patients, indicating that the technology is far from being mature. Some of the
      most common complications that plague current TAV devices include malpositioning,
      crimp-induced leaflet damage, paravalvular leak, thrombosis, conduction
      abnormalities and prosthesis-patient mismatch. In this article, we provide an in
      depth review of the current state-of-the-art pertaining the mechanics of TAVs
      while highlighting various studies guiding clinicians, regulatory agencies, and
      next-generation device designers.

PMID- 27873039
TI  - Erratum to: Improvement of gamete quality by stimulating and feeding the
      endogenous antioxidant system: mechanisms, clinical results, insights on gene
      environment interactions and the role of diet.

PMID- 27873038
TI  - The importance of nonlinear tissue modelling in finite element simulations of
      infant head impacts.
AB  - Despite recent efforts on the development of finite element (FE) head models of
      infants, a model capable of capturing head responses under various impact
      scenarios has not been reported. This is hypothesized partially attributed to the
      use of simplified linear elastic models for soft tissues of suture, scalp and
      dura. Orthotropic elastic constants are yet to be determined to incorporate the
      direction-specific material properties of infant cranial bone due to grain fibres
      radiating from the ossification centres. We report here on our efforts in
      advancing the above-mentioned aspects in material modelling in infant head and
      further incorporate them into subject-specific FE head models of a newborn, 5-
      and 9-month-old infant. Each model is subjected to five impact tests (forehead,
      occiput, vertex, right and left parietal impacts) and two compression tests. The
      predicted global head impact responses of the acceleration-time impact curves and
      the force-deflection compression curves for different age groups agree well with
      the experimental data reported in the literature. In particular, the newly
      developed Ogden hyperelastic model for suture, together with the nonlinear
      modelling of scalp and dura mater, enables the models to achieve more realistic
      impact performance compared with linear elastic models. The proposed approach for
      obtaining age-dependent skull bone orthotropic material constants counts both an
      increase in stiffness and decrease in anisotropy in the skull bone-two essential
      biological growth parameters during early infancy. The profound deformation of
      infant head causes a large stretch at the interfaces between the skull bones and
      the suture, suggesting that infant skull fractures are likely to initiate from
      the interfaces; the impact angle has a profound influence on global head impact
      responses and the skull injury metrics for certain impact locations, especially
      true for a parietal impact.

PMID- 27873043
TI  - Proceedings of the World Molecular Imaging Congress 2016, New York, New York,
      September 7-10, 2016: Late-Breaking Abstracts.

PMID- 27873041
TI  - The diagnostic challenge of the sequelae of acute pancreatitis on CT imaging: a
      pictorial essay.
AB  - PURPOSE: The purpose of the study was to present a pictorial review of the long
      term sequelae of acute pancreatitis on CT imaging as these findings can cause
      diagnostic confusion in the absence of a proper clinical history and/or prior CT
      imaging. METHODS: We retrospectively identified 81 patients who had an episode of
      acute pancreatitis with diagnostic findings on CT and also underwent one or more
      follow-up CT scans at least 1 month beyond the acute episode. The residual
      findings on all follow-up CT scans were tabulated, including the time interval
      since the initial bout of acute pancreatitis. RESULT: Residual inflammatory
      changes were present in 19.8% of cases, with a median time period lasting 86 days
      since the initial episode of acute pancreatitis. Residual fluid collections were
      seen in 27.2% and persisted for a median of 132 days. Three patients had residual
      solid-appearing inflammatory masses, which could be mistaken for neoplasms. Other
      long-term sequelae were also tabulated, including pancreatic ductal dilatation,
      pancreatic atrophy, new or increased pancreatic calcifications, biliary tract
      dilatation, central portal venous occlusion, and pseudoaneurysm formation. These
      residual findings and long-term complications are presented as a pictorial essay.
      CONCLUSION: Recognizing the spectrum of residual findings of acute pancreatitis,
      some of which can be long term, is important in the correct interpretation of a
      pancreatic CT. These findings can mimic acute pancreatitis or a
      pancreatic/peripancreatic neoplasm and often cause diagnostic confusion,
      especially in the absence of prior CT imaging.

PMID- 27873040
TI  - Can MRI predict meningioma consistency?: a correlation with tumor pathology and
      systematic review.
AB  - Tumor consistency is a critical factor that influences operative strategy and
      patient counseling. Magnetic resonance imaging (MRI) describes the concentration
      of water within living tissues and as such, is hypothesized to predict aspects of
      their biomechanical behavior. In meningiomas, MRI signal intensity has been used
      to predict the consistency of the tumor and its histopathological subtype, though
      its predictive capacity is debated in the literature. We performed a systematic
      review of the PubMed database since 1990 concerning MRI appearance and tumor
      consistency to assess whether or not MRI can be used reliably to predict tumor
      firmness. The inclusion criteria were case series and clinical studies that
      described attempts to correlate preoperative MRI findings with tumor consistency.
      The relationship between the pre-operative imaging characteristics,
      intraoperative findings, and World Health Organization (WHO) histopathological
      subtype is described. While T2 signal intensity and MR elastography provide a
      useful predictive measure of tumor consistency, other techniques have not been
      validated. T1-weighted imaging was not found to offer any diagnostic or
      predictive value. A quantitative assessment of T2 signal intensity more reliably
      predicts consistency than inherently variable qualitative analyses. Preoperative
      knowledge of tumor firmness affords the neurosurgeon substantial benefit when
      planning surgical techniques. Based upon our review of the literature, we
      currently recommend the use of T2-weighted MRI for predicting consistency, which
      has been shown to correlate well with analysis of tumor histological subtype.
      Development of standard measures of tumor consistency, standard MRI
      quantification metrics, and further exploration of MRI technique may improve the
      predictive ability of neuroimaging for meningiomas.

PMID- 27873044
TI  - Proceedings of the World Molecular Imaging Congress 2016, New York, New York,
      September 7-10, 2016: General Abstracts.

PMID- 27873045
TI  - The Interplay Between Early Father Involvement and Neonatal Medical Risk in the
      Prediction of Infant Neurodevelopment.
AB  - The current study examines the association between early father involvement and
      infant neurodevelopment, and whether neonatal medical risk moderates this
      association. Data from approximately 6000 fathers and their children were
      obtained from the Early Childhood Longitudinal Study: Birth Cohort (ECLS-B).
      Hierarchical regression was employed to analyze the data. The findings reveal
      that the association between early father involvement and infant neurodevelopment
      is contingent on both the timing of involvement (i.e., prenatal/perinatal or
      infancy) and offspring medical status at birth. The neurodevelopment of medically
      at-risk neonates was enhanced when fathers were involved during the gestational
      period and at the time of their birth. This relationship was not detected,
      however, in the case of infants who did not experience medical risks as neonates.
      Neonatal medical risk appears to be an important moderating factor in the link
      between father involvement during pregnancy and childbirth and infant
      neurodevelopment. Practitioners should continue to make efforts to involve
      fathers during gestation and childbirth. The findings of the present study
      suggest that doing so may protect against neurodevelopmental delays in neonates
      with medical risks.

PMID- 27873047
TI  - Subarachnoidal migration of intraocular silicone oil.

PMID- 27873046
TI  - Commercially available lifestyle modification program: randomized controlled
      trial addressing heart and bone health in BRCA1/2+ breast cancer survivors after
      risk-reducing salpingo-oophorectomy.
AB  - PURPOSE: The goal of this RCT was to examine the efficacy and safety of a web
      based program to improve cardiovascular and bone health outcomes, among 35
      BRCA1/2+ breast cancer survivors who underwent prophylactic oophorectomy and thus
      experienced premature surgical menopause. METHODS: A 12-month commercially
      available web-based lifestyle modification program (Precision Nutrition Coaching)
      was utilized. Cardiovascular fitness, dietary intake, leisure time activity, body
      composition, bone mineral density, bone structure, and muscle strength were
      assessed. RESULTS: Average adherence to all program components was 74.8 %. Women
      in the intervention group maintained their cardiovascular fitness level over the
      12 months (1.1 +/- 7.9 %), while the control group significantly decreased
      fitness capacity (-4.0 +/- 7.5 %). There was a significant difference between
      groups in percent change of whole body bone area (-0.8 +/- 2.5 control and 0.5 +/
      1.30 intervention). We also observed decreased BMI (-4.7 +/- 6.2 %) and fat mass
      (-8.6 +/- 12.7 %) in the intervention group due to significant concomitant
      decreases in caloric intake and increases in caloric expenditure. The control
      group demonstrated decreased caloric intake and decreased lean tissue mass.
      CONCLUSIONS: In this population at high risk for detrimental cardiovascular and
      bone outcomes, a commercially available lifestyle intervention program mitigated
      a decline in cardiovascular health, improved bone health, and decreased weight
      through fat loss. IMPLICATIONS FOR CANCER SURVIVORS: Precision Nutrition Coaching
      has shown benefit in breast cancer survivors for reduced risk of deleterious
      cardiovascular and bone outcomes.

PMID- 27873049
TI  - The quality of articles and challenges ahead.

PMID- 27873048
TI  - The usefulness of radiological grading scales to predict pain intensity,
      functional impairment, and health-related quality of life after surgery for
      lumbar degenerative disc disease.
AB  - PURPOSE: The goal of this study is to determine the relationship of radiological
      grading scales of lumbar degenerative disc disease (DDD) with postoperative pain
      intensity, functional impairment, and health-related quality of life (HRQoL).
      METHODS: Response to surgical treatment at 6 weeks (W6) on the visual analogue
      scale (VAS) for back and leg pain, Oswestry-Disability (ODI) and Roland-Morris
      Disability Index (RMDI), Timed Up and Go (TUG) test, EuroQol (EQ) 5D, and Short
      Form Health-Survey (SF-12) physical component summary (PCS) was compared between
      patients with different Modic (MOD) and Pfirrmann (PFI) grades. Longitudinal
      outcomes at day 3 (D3), W6, 6 months (M6), and 1 year (Y1) were compared.
      RESULTS: The study included 338 patients (mean age, 58.6 years), of which n = 202
      (59.8%) had MOD 1-3 and n = 217 (64.2%) PFI 4-5 changes. Patients with MOD 1-3
      were as likely as patients without MOD changes to be treatment-responders at W6
      in terms of VAS leg pain, ODI, RMDI, TUG, EQ5D, and SF-12 PCS. Similarly,
      patients with PFI 4-5 were as likely as patients with PFI 1-3 changes to be
      treatment-responders at W6. Longitudinal outcomes were similar at D3, W6, M6, and
      Y1 between patients with and without MOD changes. Patients with PFI 4-5 fared
      similar to those with PFI 1-3 except for inferior HRQoL on the SF-12 PCS metric
      at Y1. CONCLUSIONS: There was no distinct relationship between commonly used
      radiological grading scales of lumbar DDD with clinical outcome. Therefore, no
      prognosis should be made on the grounds of preoperative PFI and MOD
      classifications for patients undergoing spine surgery for lumbar DDD.

PMID- 27873050
TI  - Spontaneous regression of a parafalcine meningioma in a multiple sclerosis
      patient being treated with interferon beta-1a.
AB  - Regression of meningioma after haemorrhage and the cessation of hormone treatment
      is well reported. However, spontaneous regression is very rarely observed. Here,
      we report the spontaneous regression of a parafalcine meningioma in a 56-year-old
      woman with multiple sclerosis, who was referred to our department after an
      incidental finding on magnetic resonance imaging. She was being treated with
      interferon beta-1a to manage the symptoms. To our knowledge, this is the first
      report of spontaneous regression of meningioma in a patient receiving interferon
      beta-1a therapy and just the second report of spontaneous regression in general.

PMID- 27873051
TI  - Clinical and radiological course of intracerebral haemorrhage associated with the
      new non-vitamin K anticoagulants.
AB  - BACKGROUND: Clinical outcome and mortality in intracerebral haemorrhage (ICH)
      associated with anticoagulant treatment is poor. Novel direct oral anticoagulant
      drugs (NOACs) are increasingly prescribed. Management of NOAC-associated ICH
      might be more challenging. The aim of this study was to compare the clinical and
      radiological course of ICH patients being treated with different forms of oral
      anticoagulant drugs. METHOD: The study is a retrospective observational study.
      Haemorrhage in other intracranial compartments except the ventricular system were
      explicitly excluded. Four groups were categorised and compared with regard to
      their clinical and radiological course (NOACs, vitamin K antagonists [VKAs],
      platelet inhibitors and patients without anticoagulant/antiplatelet drugs).
      Clinical as well as radiological parameters were analysed. RESULTS: Overall, 182
      patients were included (2011 to early 2016). Twenty-five patients with NOAC
      associated ICH were included (47 with VKAs, 50 with platelet inhibitors and 60
      patients without anticoagulant/antiplatelet drugs). The frequency of NOAC
      associated ICH increased over the years. Diabetes was found significantly more
      often in the NOAC patients (p = 0.05). The clinical and radiological courses in
      the three different patient groups with impaired coagulation were similar.
      Mortality was significantly higher in patient groups with impaired coagulation (p
      = 0.04) compared to those without anticoagulant/antiplatelet drugs. Multivariate
      analysis revealed the Glasgow Coma Scale (GCS) score as a strong predictor for
      worse outcome and mortality. CONCLUSIONS: The frequency of NOAC-associated ICH
      increased in the last 5 years. Diabetes might be a risk factor for ICH when
      receiving NOACs. Clinical outcome in NOAC-associated ICH is poor and mortality is
      as high as in patients with other oral anticoagulant/antiplatelet drugs.

PMID- 27873052
TI  - Symptoms of uterine myomas: data of an epidemiological study in Germany.
AB  - PURPOSE: Currently, no reliable data are available concerning the type and
      frequency of symptoms in premenopausal women with uterine myomas. METHODS: 2296
      women were examined by means of vaginal ultrasound for the presence of myomas in
      seven gynaecological outpatient departments in Germany. From this population,
      1314 premenopausal women between the ages of 30 and 55 years were evaluated to
      determine the type and frequency of myoma-related symptoms and their relationship
      to anamnestic factors, and the number, size, and location of the myomas.
      Standardised questionnaires were used to record the symptoms. RESULTS:
      Prevalence: In almost every second premenopausal woman (n = 639; 48.6%), uterine
      myomas were diagnosed. The frequency of myomas increased continuously with age
      and was highest in women between 46 and 50 years (65.2%). Age itself was found to
      be the main risk factor for the presence of myomas (p < 0.001). SYMPTOMS: 54.3%
      (n = 347) of the women suffered from myoma-related symptoms. The four main
      symptoms were identified as: Heavy menstrual bleeding (40.7%), dysmenorrhoea
      (28.2%), lower abdominal pain (14.9%), and intermenstrual bleeding (14.1%). In
      the majority of cases, the symptoms occurred simultaneously. Determinants for
      symptoms: Symptoms did not follow a clear age-related trend, whilst the number
      and size of the myomas did determine the presence of symptoms. The main
      influencing factor for the presence of intermenstrual bleeding was the location
      of the myomas. CONCLUSIONS: The high prevalence of uterine myomas highlights the
      importance of the diagnosis uterine myomas in standard gynaecological practice:
      The presence of only one myoma caused symptoms in 46.5% and small myomas of up to
      2 cm in diameter resulted in symptoms in 39.5%.

PMID- 27873053
TI  - Relationship between the mechanism of hepatitis B virus father-infant
      transmission and pregnancy outcome.
AB  - PURPOSE: This study examined the relationship between the mechanism of hepatitis
      B virus (HBV) father-infant transmission via reproductive cells and pregnancy
      outcome. METHODS: Abandoned in vitro fertilization (IVF) embryos of fathers with
      chronic HBV infection were taken as study objects. HBV mRNA in embryos was
      detected, and successfully transplanted embryos were followed up to determine the
      relationship between HBV-infected embryos and pregnancy outcome. RESULTS: HBV
      mRNA signals were detected in one embryo in the group with HBV-positive fathers;
      the positive rate was 1/18 (5.5%). IVF embryos of HBV-positive fathers with HBV
      mRNA signals were successfully implanted, but early abortion occurred.
      CONCLUSIONS: HBV mRNA was found in abandoned IVF embryos of HBV-infected fathers,
      which confirmed that HBV could not only enter early cleavage embryos via sperm
      but also replicate in embryos, resulting in HBV father-infant transmission. HBV
      may interfere with embryonic development and thus affect pregnancy outcome.

PMID- 27873054
TI  - Expectant management may reduce overtreatment in women affected by unexplained
      infertility confirmed by diagnostic laparoscopy.
AB  - PURPOSE: To determine whether the mini-invasive surgery still play a role in the
      diagnostic workup and in the management of the couples affected by unexplained
      infertility. METHODS: 170 infertile women (age range 25-38 years) with documented
      normal ovarian, tubal and uterine function underwent combined hysteroscopic and
      laparoscopic surgery; 100 women refused surgery or ART treatment (control group)
      choosing expectant management. A retrospective assessment questionnaire was
      proposed to enrolled women to collect the rate of spontaneous or ART-induced
      pregnancies. RESULTS: The combined surgery revealed pelvic pathologies in 49.4%
      of patients, confirming the diagnosis of unexplained infertility only in 86 of
      studied patients. In this group of 86 selected women, 28 of them achieved a
      spontaneous pregnancy and 23 women obtained pregnancy after ART. The Chi-square
      analysis shows that the pregnancy rate was not influenced by the employment of
      ART. In the group of 100 control women, only 14 (14%) achieved a spontaneous
      pregnancy after 18 months of expectant management. CONCLUSIONS: Combined
      laparoscopy and hysteroscopy in women with unexplained infertility may reveal
      previously undiagnosed pathologies that could require ART, and in those without
      abnormal surgical finding, ART does not improve pregnancy rate.

PMID- 27873055
TI  - HIV-Related Stress and Life Chaos Mediate the Association Between Poverty and
      Medication Adherence Among People Living with HIV/AIDS.
AB  - HIV treatment depends on high-levels of antiretroviral therapy (ART) adherence,
      which is severely impeded by poverty. Men and women living with HIV infection (N
      = 92) completed computerized interviews of demographic and health
      characteristics, poverty markers, stressful life events, and life chaos, as well
      as unannounced pill counts to determine prospective medication adherence and
      medical record chart abstractions for HIV viral load. Poverty markers were
      associated with both stressors and chaos, and the direct effects of all three
      factors predicted ART non-adherence. The multiple mediation model showed that
      accounting for stressors and chaos resulted in a non-significant association
      between poverty markers and ART adherence. The indirect effect of poverty markers
      on adherence through life chaos was significant, whereas the indirect effect of
      poverty markers on adherence through stressors was not significant. Factors that
      render HIV-related stress and create chaos offer intervention targets that are
      more amenable to change than poverty itself.

PMID- 27873056
TI  - Individual Pheromone Signature in Males: Prerequisite for Pheromone-Mediated Mate
      Assessment in the Central American Locust, Schistocerca Piceifrons.
AB  - Living in high-density groups of animals has advantages and disadvantages for
      mating. The advantage of facilitated mate finding is compromised by difficulties
      in protecting a suitable partner from competitors. Thus, males regularly are
      faced with increased competition for sperm, and females with harassment by males
      at high population densities. To cope with these problems, mating tactics and
      mate choice mechanisms have to be adjusted. An adaptation to gregarious condition
      observed in locusts includes the use of male-emitted pheromones. Males of the
      Central American locust, Schistocerca piceifrons, release sex-specific volatiles,
      which were identified as phenethyl alcohol (synonym: phenyl-ethyl-alcohol, 2
      phenyl-1-ethanol, 2-phenylethanol, PEA), (Z)-3-nonen-1-ol (3-Nol), and (Z)-2
      octen-1-ol (2-Ool). The emission of the two major compounds, PEA and 3-Nol, was
      restricted to crowded conditions. Furthermore, the release of both volatiles was
      coupled to males reaching sexual maturity, indicating a function in reproductive
      behavior. However, neither the single substances nor their mixtures were
      attractive or repellent to the locusts. Instead, females prefer the sperm of high
      pheromone-emitting males to fertilize their ova. In this way, the male-specific
      volatiles act as mate assessment pheromones utilized in a context of cryptic
      female choice. This function is well supported by the highly variable but
      individual-specific emission rates of the three compounds. Schistocerca
      piceifrons males release a virtually unique personal pheromone signature, a
      prerequisite for mate assessment pheromones.

PMID- 27873058
TI  - Prediction of the Reverse Micellar Extraction of Papain Using Dissipative
      Particle Dynamics Simulation.
AB  - Reverse micellar extraction is a promising technology for large-scale protein
      purification, but its molecular interaction mechanisms have not been thoroughly
      characterized. In this study, a dissipative particle dynamics (DPD) molecular
      simulation method was employed to study the interactions among the surfactant,
      organic phase, water, and proteins on the mesoscopic scale. This study simulated
      the self-assembly process of the reverse micelle extraction of papain. The
      results showed that the papain could be extracted by a CTAB/isooctane/n-hexanol
      system, which was validated by extraction experiments. The optimized extraction
      recovery was 76.9 %. This study elucidates the molecular process of the reverse
      micellar extraction of proteins and provides a method to predict its efficacy.

PMID- 27873057
TI  - Threat of Deportation as Proximal Social Determinant of Mental Health Amongst
      Migrant Workers.
AB  - While migration health studies traditionally focused on socioeconomic
      determinants of health, an emerging body of literature is exploring migration
      status as a proximate cause of health outcomes. Study 1 is a path analysis of the
      predictors of mental health amongst 582 documented migrant workers in Singapore,
      and shows that threat of deportation is one of the most important proximate
      social determinants of predicted mental illness, and a mediator of the impact of
      workplace conflict on mental health. Study 2 is a qualitative study of the
      narratives of 149 migrant workers who were in workplace conflict with their
      employers, and demonstrates that workers believed threats were used as a
      negotiating strategy during workplace conflicts. Findings suggest that migration
      status places workers who come into workplace conflict with their employers at
      heightened risk of mental illness because migration status can be used as a tool
      by employers in workplace negotiations.

PMID- 27873059
TI  - The effect of Daikenchuto on postoperative intestinal motility in patients with
      right-side colon cancer.
AB  - PURPOSE: Daikenchuto (DKT) has a stimulant effect on intestinal motility and
      reportedly has a positive effect on postoperative intestinal motility in patients
      with sigmoid colon cancer. In this study, we investigated the effects of DKT in
      patients with right-side colon cancer. METHODS: This retrospective study included
      88 patients with right-side colon cancer. We orally administered 7.5 g of DKT in
      the DKT group and did not administer any DKT to patients in the no-DKT group. All
      patients ingested radiopaque markers 2 h before surgery, which were used to
      assess intestinal motility. The postoperative intestinal motility was
      radiologically assessed by counting the numbers of residual markers in the large
      and small intestines. RESULTS: The DKT and no-DKT groups showed no marked
      differences in the total number of residual markers or number of residual markers
      in the small intestine. However, in the elderly subgroup, the total number of
      residual markers in the DKT group was significantly less than in the no-DKT
      group. CONCLUSION: Although DKT had some small effect on the postoperative
      intestinal motility for most patients, it may have positive effects in elderly
      patients.

PMID- 27873060
TI  - Reinforced mitral valve replacement using a xenopericardium collared prosthetic
      valve for a heavily calcified or disrupted mitral annulus: a simple "Dumpling
      technique".
AB  - Heavy mitral annular calcification or severe destruction of the mitral annulus in
      the setting of mitral valve replacement may result in fatal complications, such
      as atrioventricular disruption, ventricular rupture, valve dehiscence, and
      perivalvular leakage. Collar-reinforced mitral valve replacements with
      xenopericardium have been reported to prevent perivalvular leakage and valve
      detachment. We herein describe our experience with an easy method of handling the
      modified collar-reinforced prosthetic valve, which we call the "Dumpling
      technique", in six patients.

PMID- 27873062
TI  - [Masquerades and Trojans : When tumors disguise as uveitis].

PMID- 27873061
TI  - [Opacification of a hydrophilic acrylic intraocular lens after DMEK : A material
      analysis].
AB  - OBJECTIVE: Calcification of a hydrophilic intraocular lens (IOL) is a rare
      complication. We report on the analysis of an opacified IOL, which was explanted
      2 years after Descemet membrane endothelial keratoplasty (DMEK), using light and
      scanning electron microscopy, X-ray spectroscopy and investigations on the
      optical bench. METHODS: In October 2012 a patient with pseudophakic keratopathy
      and Fuchs endothelial dystrophy underwent DMEK with double rebubbling. Due to
      primary graft failure the patient underwent penetrating keratoplasty in January
      2013. The initial postoperative visual acuity was 0.2. Increasing opacification
      of the IOL lowered visual acuity down to hand movement, so that in November 2014
      the patient underwent IOL replacement. The explanted IOL was first natively
      examined with an Olympus BX50 light microscope. In addition, image quality was
      determined on the optical bench. Subsequently, the explanted IOL was divided into
      two and one half was stained with Alizarin red and von Kossa and examined by
      light microscopy and the other half was analyzed by scanning electron microscopy.
      The composition of the deposits was examined by X-ray spectroscopy. RESULTS: The
      macroscopic view showed opacification of the IOL only in the central area of the
      lens where contact between the IOL and the gas bubble had taken place. Light and
      scanning electron microscopy revealed numerous fine granular, crystal-like
      deposits under the anterior IOL surface, which were linearly arranged parallel to
      the surface. Using energy dispersive X-ray spectroscopy the deposits were shown
      to be composed of calcium phosphate. No deposits were detected on the posterior
      surface. CONCLUSION: The cause of the opacification of hydrophilic IOL is not
      clearly understood; however, the injection of gas/air into the anterior chamber
      during DMEK appears to increase the risk of IOL opacification by changing the
      lens surface or by alterations to the blood-aqueous humor barrier. Granular
      deposits under the anterior IOL surface can cause such a strong decrease in
      visual acuity that IOL exchange becomes neccessary.

PMID- 27873063
TI  - [A new technique to facilitate donor preparation for DMEK surgery].
AB  - BACKGROUND: Descemet membrane endothelial keratoplasty (DMEK) is becoming more
      and more the method of choice to treat corneal endothelial diseases in
      specialized centers. The reasons that prevent this technique from becoming
      widespread are the delicate donor tissue preparation. By inverting the curvature
      of the cornea from convex to concave after mounting onto an artificial anterior
      chamber, we developed a combined manual delamination and hydrodissection
      technique, which allows a rapid and endothelium-preserving method of separating
      donor Descemet membranes from the underlying stroma. MATERIAL AND METHODS:
      Experiments were perfomed with 60 donor corneas that were not suitable for
      transplantation. Donor age ranged between 42 and 94 years. Two experimental
      groups were formed: 1 inverse manual delamination (n = 16) and 2 combined manual
      delamination and hydrodissection (n = 44). All experiments were undertaken by an
      experienced surgeon who was, however, not experienced with these techniques. We
      examined the frequency of Descemet membrane rupture as well as the amount of
      induced endothelial damage (trypan blue staining with quantitative image
      analysis). RESULTS: Significant lesions of Descemet's membrane that would have
      led to a loss of the graft occurred in 25% of the manual delamination cases and
      in 4.5% using the combined technique. Endothelial damage induced by both
      techniques was low (6 and 5.2%, respectively). CONCLUSION: For DMEK donor
      preparation, a combination of manual delamination and hydrodissection was shown
      to be a safe and endothelium-protective technique to separate Descemet membranes
      from the underlying stroma. A very rapid learning curve for the combination
      technique is of specific additional interest for beginners in DMEK surgery.

PMID- 27873065
TI  - Decline in territory size and fecundity as a response to carrying capacity in an
      endangered songbird.
AB  - Density-dependent processes are fundamental mechanisms for the regulation of
      populations. Ecological theories differ in their predictions on whether
      increasing population density leads to individual adjustments of survival and
      reproductive output or to dominance and monopolization of resources. Here, we use
      a natural experiment to examine which factors limit population growth in the only
      remaining population of the endangered pale-headed brush finch (Atlapetes
      pallidiceps). For three distinct phases (a phase of population suppression, 2001
      2002; expansion due to conservation management, 2003-2008; and equilibrium phase,
      2009-2014), we estimated demographic parameters with an integrated population
      model using population size, the proportion of successfully breeding pairs and
      their productivity, territory size, and mark-recapture data of adult birds. A low
      proportion of successful breeders due to brood parasitism (0.42, 95% credible
      interval 0.26-0.59) limited population growth before 2003; subsequent culling of
      the brood parasite resulted in a two-fold increase of the proportion of
      successful breeders during the 'expansion phase'. When the population approached
      the carrying capacity of its habitat, territory size declined by more than 50%
      and fecundity declined from 1.9 (1.54-2.27) to 1.3 (1.12-1.53) chicks per
      breeding pair, but the proportion of successful breeders remained constant
      (expansion phase: 0.85; 0.76-0.93; equilibrium phase: 0.86; 0.79-0.92). This
      study demonstrates that limiting resources can lead to individual adjustments
      instead of despotic behavior, and the individual reduction of reproductive output
      at high population densities is consistent with the slow life-history of many
      tropical species.

PMID- 27873066
TI  - Diverse foraging opportunities drive the functional response of local and
      landscape-scale bear predation on Pacific salmon.
AB  - The relationship between prey abundance and predation is often examined in single
      habitat units or populations, but predators may occupy landscapes with diverse
      habitats and foraging opportunities. The vulnerability of prey within populations
      may depend on habitat features that hinder predation, and increased density of
      conspecifics in both the immediate vicinity and the broader landscape. We
      evaluated the relative effects of physical habitat, local, and neighborhood prey
      density on predation by brown bears on sockeye salmon in a suite of 27 streams
      using hierarchical Bayesian functional response models. Stream depth and width
      were inversely related to the maximum proportion of salmon killed, but not the
      asymptotic limit on total number killed. Interannual variation in predation was
      density dependent; the number of salmon killed increased with fish density in
      each stream towards an asymptote. Seven streams in two geographical groups with
      >=23 years of data in common were then analyzed for neighborhood density effects.
      In most (12 of 18) cases predation in a stream was reduced by increasing salmon
      abundance in neighboring streams. The uncertainty in the estimates for these
      neighborhood effects may have resulted from interactions between salmon abundance
      and habitat that influenced foraging by bears, and from bear behavior (e.g.,
      competitive exclusion) and abundance. Taken together, the results indicated that
      predator-prey interactions depend on density at multiple spatial scales, and on
      habitat features of the surrounding landscape. Explicit consideration of this
      context dependency should lead to improved understanding of the ecological
      impacts of predation across ecosystems and taxa.

PMID- 27873064
TI  - Development of diffuse large B-cell lymphoma from follicular lymphoma of the
      duodenum: changes in endoscopic findings during a 6-year follow-up.
AB  - A 71-year-old Japanese man was diagnosed as having stage I primary follicular
      lymphoma (FL) of the duodenum according to Lugano International Conference
      Classification and began receiving annual checkups. Endoscopic examination
      disclosed white villi swelling with depressed red mucosal lesions. Biopsy
      specimens from the area of white villi exhibited histopathological features that
      met the diagnostic criteria for low-grade FL. The depressed red lesions gradually
      enlarged over six years of follow-up. A biopsy of the white villi swelling
      revealed distinct well-circumscribed follicles with attenuated mantles in the
      lamina propria that were positive for CD20, bcl-2, and CD10. Histological
      findings from the depressed red lesions at 5.5 years after the initial diagnosis
      were compatible for FL. However, biopsy specimens 6 months later obtained from
      the same lesions showed a mixture of larger mononuclear cells. These follicular
      cells were positive for CD20 and bcl-2, but not for CD10, indicating the presence
      of diffuse large B-cell lymphoma (DLBCL). This case shows altered endoscopic
      findings in the course of DLBCL development from FL. When depressed red lesions
      are detected in the background of white villi swelling, repeated biopsies should
      be performed from both lesions.

PMID- 27873067
TI  - Effectiveness of baseline corticosterone as a monitoring tool for fitness: a meta
      analysis in seabirds.
AB  - Many ecosystems have experienced anthropogenically induced changes in
      biodiversity, yet predicting these patterns has been difficult. Recently,
      individual behavioural and physiological measures have been proposed as more
      rapid links between environmental variation and fitness compared to demographics.
      Glucocorticoid hormones have received much attention given that they mediate
      energetic demands, metabolism, and foraging behaviour. However, it is currently
      unclear whether glucocorticoids can reliably predict environmental and fitness
      related traits and whether they may be useful in specific groups of taxa. In
      particular, seabirds are a well-studied avian group often employed as
      biomonitoring tools for environmental change given their wide distribution and
      reliance on large oceanic patterns. Despite the increase in studies attempting to
      link variation in baseline corticosterone (the primary avian glucocorticoid) to
      variation in fitness-related traits in seabirds, there has been no comprehensive
      review of the relationship in this taxon. We present a phylogenetically
      controlled systematic review and meta-analysis of correlative and experimental
      studies examining baseline corticosterone as a predictor of fitness-related
      traits relevant to predicting seabird population health. Our results suggest
      that, while variation in baseline corticosterone may be a useful predictor of
      larger-scale environmental traits such as overall food availability and fitness
      related traits such as reproductive success, this hormone may not be sensitive
      enough to detect variation in body condition, foraging effort, and breeding
      effort. Overall, our results support recent work suggesting that the use of
      baseline glucocorticoids as conservation biomarkers is complex and highly context
      dependent, and we suggest caution in their use and interpretation as simplified,
      direct biomarkers of fitness.

PMID- 27873068
TI  - Theoretical insights into [NiFe]-hydrogenases oxidation resulting in a slowly
      reactivating inactive state.
AB  - [NiFe]-hydrogenases catalyse the relevant H2 -> 2H+ + 2e- reaction. Aerobic
      oxidation or anaerobic oxidation of this enzyme yields two inactive states called
      Ni-A and Ni-B. These states differ for the reactivation kinetics which are slower
      for Ni-A than Ni-B. While there is a general consensus on the structure of Ni-B,
      the nature of Ni-A is still controversial. Indeed, several crystallographic
      structures assigned to the Ni-A state have been proposed, which, however, differ
      for the nature of the bridging ligand and for the presence of modified cysteine
      residues. The spectroscopic characterization of Ni-A has been of little help due
      to small differences of calculated spectroscopic parameters, which does not allow
      to discriminate among the various forms proposed for Ni-A. Here, we report a DFT
      investigation on the nature of the Ni-A state, based on systematic explorations
      of conformational and configurational space relying on accurate energy
      calculations, and on comparisons of theoretical geometries with the X-ray
      structures currently available. The results presented in this work show that,
      among all plausible isomers featuring various protonation patterns and oxygenic
      ligands, the one corresponding to the crystallographic structure recently
      reported by Volbeda et al. (J Biol Inorg Chem 20:11-22, 19)-featuring a bridging
      hydroxide ligand and the sulphur atom of Cys64 oxidized to bridging sulfenate-is
      the most stable. However, isomers with cysteine residues oxidized to terminal
      sulfenate are very close in energy, and modifications in the network of H-bond
      with neighbouring residues may alter the stability order of such species.

PMID- 27873071
TI  - Development of a fluorescence resonance energy transfer-based intracellular assay
      to identify novel enterovirus 71 antivirals.
AB  - Enterovirus 71 (EV71) is considered one of the most virulent pathogens in the
      family Picornaviridae. However, there have been no effective treatments for the
      severe complications caused by EV71. Development of new drugs against targets
      that are essential for viral replication often requires screening large
      collections of compounds, for which a high-throughput screening platform is
      needed. In this study, a drug-screening platform was developed based on a
      genetically engineered cell line that displays fluorescence resonance energy
      transfer (FRET) and shows a real-time and quantifiable impairment of FRET upon
      EV71 infection. A library of small molecules consisting of 1280 compounds with
      defined bioactivities was used for screening drugs with anti-EV71 activity;
      accurate, rapid, and robust results were obtained from this screening procedure.
      Ten drugs were identified in the primary screening, and their antiviral
      activities were indicated by dose-dependent elevation of FRET. Among these, AC
      93253, mitoxantrone and N-bromoacetamide had not been reported as enterovirus
      inhibitors, and it was confirmed that they were able to suppress viral yields in
      a dose-dependent manner. Taken together, these studies demonstrate the
      feasibility of this FRET-based platform for efficient screening and
      identification of novel compounds with activity against EV71 infection.

PMID- 27873070
TI  - Highly pathogenic avian influenza (H5N1) in Nigeria in 2015: evidence of
      widespread circulation of WA2 clade 2.3.2.1c.
AB  - Genetic analysis of the complete haemagglutinin (HA) gene of fourteen Nigerian
      avian influenza isolates showed multiple basic amino acids at the cleavage site
      (321PQRERRRK del R*GLF333), characteristic of highly pathogenic avian influenza
      (HPAI). Substitution of Gln to Lys at position 322 (H5-specific numbering) was
      identified in one isolate. In some isolates, amino acid substitutions were
      observed across the HA gene, however the receptor binding, antigenic and
      glycosylation sites were conserved in all. Phylogenetic analysis revealed two
      clusters of the HPAI H5N1 clade 2.3.2.1c. Cluster I has close genetic relatedness
      (97.8-99.8%) with viruses circulating in some West Africa countries. Cluster II
      shared close identity (98.9-100.0%) with isolates from Europe, Cote d'Ivoire and
      Niger and viruses from this cluster were detected in five of the eleven states
      investigated in Nigeria. In view of the continuous HPAI outbreaks being recorded
      in Nigerian poultry and the zoonotic potential of the virus, extensive and
      continued characterization of HPAI isolates is advocated.

PMID- 27873069
TI  - Estimated dietary intake and major food sources of polyphenols in elderly of
      Vicosa, Brazil: a population-based study.
AB  - PURPOSE: Epidemiological studies have remarked the beneficial role that
      polyphenols may have in the elderly population such as cancer and cardiovascular
      disease prevention. This is particularly relevant considering the global tendency
      of population aging. Data on polyphenol intake in the elderly population are
      scarce and usually provide partial information-only for some polyphenol classes.
      The aim of this study was to estimate the intake of polyphenols and its major
      dietary contributors in the population of Vicosa. METHODS: A cross-sectional
      population-based survey including 620 elderly was conducted in Vicosa, Brazil.
      Food intake was estimated by recall of habitual consumption (RHC). Polyphenol
      intake was calculated by matching food consumption data from the RHC with the
      polyphenol content in foods listed in the Phenol-Explorer database. RESULTS: The
      average total polyphenol intake was 1198.6 mg/day (533.7 mg/day as aglycone). The
      main polyphenol classes were phenolic acids (729.5 mg/day) and flavonoids (444.7
      mg/day). The main dietary contributors for total polyphenols were coffee (45.8%),
      beans (32.8%) and polenta (1.3%). A total of 292 polyphenols divided in 14
      classes and 23 subclasses were found. The individual compounds with the highest
      intake were isomers of chlorogenic acid (i.e., 5-caffeoylquinic acid, 4
      caffeoylquinic acid and 3-caffeoylquinic acid) among hydroxycinnamic acids that
      largely originated from coffee. CONCLUSIONS: The data reported here can be used
      to evaluate the association between the amount and type of ingested polyphenols
      and health outcomes in epidemiological studies in order to eventually establish
      nutritional recommendations.

PMID- 27873072
TI  - Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with
      parathyroid cancer and intractable primary hyperparathyroidism.
AB  - Pharmacological treatment of hypercalcemia is essential for patients with
      parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of
      the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such
      patients. We investigated the efficacy and safety of cinacalcet in Japanese
      patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients
      with parathyroid carcinoma and two with intractable PHPT were enrolled in an open
      label, single-arm study consisting of titration and maintenance phases.
      Cinacalcet doses were titrated until the albumin-corrected serum calcium
      concentration decreased to 10.0 mg/dL or less or until dose escalation was
      considered not necessary or feasible. Serum calcium concentration at the baseline
      was 12.1 +/- 1.3 mg/dL (mean +/- standard deviation; range 10.4-14.6 mg/dL) and
      decreased to 10.1 +/- 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the
      titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At
      the end of the titration phase, at least a 1 mg/dL reduction in serum calcium
      concentration from the baseline was observed in five patients (three with
      carcinoma and two with PHPT), and it decreased to the normocalcemic range in five
      patients (three with carcinoma and two with PHPT). Common adverse events were
      nausea and vomiting. One patient discontinued participation in the study because
      of an adverse event, liver disorder. Cinacalcet effectively relieved
      hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and
      might be effective in those with intractable PHPT. The drug might be tolerable
      and safe at a dosage of at most 75 mg three times a day.

PMID- 27873074
TI  - A cross-sectional study of the association between adipokine levels and bone
      mineral density according to obesity and menopausal status in Korean women.
AB  - Results regarding the association between adipokine levels and bone mineral
      density (BMD) have been inconsistent; the effects of sex, menopause, and central
      obesity remain unknown. We evaluated the association between serum leptin,
      adiponectin, and high-molecular-weight (HMW) adiponectin levels and BMD according
      to menopause and central obesity status in Korean women. This cross-sectional
      study comprised 255 women undergoing examinations at the CHA Bundang Medical
      Center. Participants were divided according to menopause, and central obesity
      status. We measured serum adipokine levels and BMD using an enzyme-linked
      immunosorbent assay and dual-energy X-ray absorptiometry, respectively. After
      adjusting for age, body mass index, alkaline phosphatase levels and the
      Homeostasis Model Assessment index, leptin levels were negatively associated with
      non-vertebral BMD (total hip, beta = -0.576, P = 0.006; femoral neck, beta = 
      0.608, P = 0.007) in postmenopausal women without central obesity. Among women
      without central obesity, HMW adiponectin levels were positively associated with
      total hip BMD (beta = 0.240, P = 0.010) in premenopausal women but negatively
      associated with BMD (lumbar, beta = -0.436, P = 0.012; femoral neck, beta = 
      0.468, P = 0.007) in postmenopausal women. Thus, the association between
      adipokine levels and BMD varies according to the menopause and central obesity
      status.

PMID- 27873073
TI  - MiR-5100 promotes osteogenic differentiation by targeting Tob2.
AB  - MicroRNAs have emerged as pivotal regulators in various physiological and
      pathological processes, including osteogenesis. Here we discuss the contribution
      of miR-5100 to osteoblast differentiation and mineralization. We found that miR
      5100 was upregulated during osteoblast differentiation in ST2 and MC3T3-E1 cells.
      Next, we verified that miR-5100 can promote osteogenic differentiation with gain
      of-function and loss-of-function experiments. Target prediction analysis and
      experimental validation demonstrated that Tob2, which acts as a negative
      regulator of osteogenesis, was negatively regulated by miR-5100. Furthermore, we
      confirmed that the important bone-related transcription factor osterix, which can
      be degraded by binding to Tob2, was influenced by miR-5100 during osteoblast
      differentiation. Collectively, our results revealed a new molecular mechanism
      that fine-tunes osteoblast differentiation through miR-5100/Tob2/osterix
      networks.

PMID- 27873075
TI  - Increased risk of hip fractures in Korean patients with type 2 diabetes: a 6-year
      nationwide population-based study.
AB  - We compared the incidence and risk of hip fractures in Korean patients with type
      2 diabetes and non-diabetic subjects in a nationwide population-based study. The
      study included 17,110 patients diagnosed with type 2 diabetes in 2004 and 34,220
      randomly selected age- and sex-matched control subjects drawn from the Korean
      National Health Insurance Research database. Fracture events occurring between
      2004 and 2010 were identified from medical claims data. The adjusted hazard
      ratios (HRs) and 95% confidence intervals (CIs) for fractures associated with
      diabetes were calculated. A total of 3855 fractures of any type (3029 in females
      and 826 in males) and 493 hip fractures (353 in females and 140 in males) were
      observed in 51,330 subjects over a 6-year follow-up period. The risk of hip
      fractures was significantly higher in female (HR 1.73; 95% CI 1.38-2.16) and male
      (HR 1.84; 95% CI 1.29-2.63) diabetics than in non-diabetic controls after
      adjusting for multiple confounders. Stratification by age revealed that the
      adjusted HR for hip fractures was highest in diabetic patients aged 50-64 years
      (HR 2.54 in females and 2.70 in males) and decreased with increasing age. The
      risk of other fractures did not differ between the groups. Korean males and
      females with type 2 diabetes are at an increased risk of hip fractures compared
      with non-diabetic individuals. Osteoporosis assessments and fracture prevention
      strategies are necessary for Koreans with type 2 diabetes.

PMID- 27873076
TI  - The association of testosterone, sex hormone-binding globulin, and insulin-like
      growth factor-1 with bone parameters in Korean men aged 50 years or older.
AB  - Testosterone and insulin-like growth factor-1 (IGF-1) are essential factors for
      the maintenance of bone health in men. However, the results for the association
      of testosterone and IGF-1 with bone parameters were not consistent in prior
      studies. We evaluated the relationship of testosterone, sex hormone-binding
      globulin (SHBG), and IGF-1 with bone mineral density (BMD) and bone turnover
      markers (BTMs) in Korean men. We enrolled 1227 men aged >=50 years in this cross
      sectional study. Serum levels of total testosterone (TT), SHBG, IGF-1,
      osteocalcin, and C-terminal cross-linking telopeptide of type I collagen (CTX)
      were measured. Free testosterone (FT) was calculated using Vermeulen's method.
      BMD was measured by dual-energy X-ray absorptiometry. TT level was not related to
      BMD or BTMs in the unadjusted model; however, after adjusting for SHBG and IGF-1,
      the association between TT and BTMs was significant (beta = -0.139 for
      osteocalcin and beta = -0.204 for CTX). SHBG levels were negatively associated
      with lumbar BMD, and positively associated with BTMs in all models. As SHBG level
      increased, the prevalence of osteopenia or osteoporosis defined by BMD
      significantly increased (OR of 1SD change, 1.24). IGF-1 levels were significantly
      related with BMD, but not with BTMs. Meanwhile, FT levels were positively
      associated with BMD and negatively associated with BTMs. In conclusion, SHBG
      levels were independently related with bone parameters and osteopenia in men aged
      >=50 years. IGF-1 levels were positively associated with BMD, but not with BTMs.
      SHBG may play a role in regulating age-related bone loss in men after middle-age.

PMID- 27873077
TI  - Impaired osteogenic differentiation and enhanced cellular receptor of advanced
      glycation end products sensitivity in patients with type 2 diabetes.
AB  - Preclinical studies have demonstrated impaired osteoblast differentiation in type
      2 diabetes (T2DM), which is related to skeletal accumulation of advanced
      glycation end products (AGEs). However, the role of AGE in osteoblast
      differentiation in patients with T2DM is unclear. This cross-sectional study was
      performed to investigate osteoblast differentiation and its association with
      serum pentosidine and soluble receptor of AGEs (sRAGE). Twenty-seven patients
      with T2DM and 15 age-matched controls were included to measure sRAGE and
      osteogenic differentiation in mononuclear cells derived from peripheral blood.
      The mononuclear cells isolated from patients with T2DM showed a significantly
      lower rate of osteogenic differentiation (7.4% vs 86.7%, p < 0.0001) with a lower
      level of ALPL, COL1A1, and BGLAP expression than those of controls by 11-, 44-,
      and 15-fold respectively, together with nonvisualized mineralization by alizarin
      red S staining. The levels of pentosidine and sRAGE were comparable in both
      groups. AGER expression was significantly higher in the T2DM group. BAX
      expression was also significantly higher in the T2DM group, and showed a strong
      correlation with AGER expression (r = 0.86, p < 0.0001). Fasting plasma glucose
      (FPG) level, AGER expression, and BAX expression showed a strong correlation with
      osteogenic differentiation defects on univariate analysis. However, only FPG
      showed a correlation with this defect in a multivariate analysis. In conclusion,
      patients with T2DM showed impairment of osteoblast differentiation, and FPG was
      an independent risk factor for this impairment. Moreover, T2DM showed a higher
      cellular sensitivity for activation of receptor of AGEs and higher cellular
      apoptosis, which may contribute to the defect in osteoblast differentiation.

PMID- 27873078
TI  - Advances in decoding breast cancer brain metastasis.
AB  - The past decade has witnessed impressive advances in cancer treatment ushered in
      by targeted and immunotherapies. However, with significantly prolonged survival,
      upon recurrence, more patients become inflicted by brain metastasis, which is
      mostly refractory to all currently available therapeutic regimens. Historically,
      brain metastasis is an understudied area in cancer research, partly due to the
      dearth of appropriate experimental models that closely simulate the special
      biological features of metastasis in the unique brain environment and to the
      sophistication of techniques required to perform in-depth studies of the
      extremely complex and challenging brain metastasis. Yet, with increasing clinical
      demand for more effective treatment options, brain metastasis research has
      rapidly advanced in recent years. The present review spotlights the recent major
      progresses in basic and translational studies of brain metastasis with focuses on
      new animal models, novel imaging technologies, omics "big data" resources, and
      some new and exciting biological insights on brain metastasis.

PMID- 27873080
TI  - Evaluation of the drug solubility and rush ageing on drug release performance of
      various model drugs from the modified release polyethylene oxide matrix tablets.
AB  - Hydrophilic matrix systems are currently some of the most widely used drug
      delivery systems for controlled-release oral dosage forms. Amongst a variety of
      polymers, polyethylene oxide (PEO) is considered an important material used in
      pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is
      susceptible to free radical oxidative attack. The aim of this study was to
      investigate the stability of PEO based formulations containing different model
      drugs with different water solubility, namely propranolol HCl, theophylline and
      zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers
      for the manufacture of tablets stored at 40  degrees C. The results of the
      present study suggest that the drug release from the matrix was affected by the
      length of storage conditions, solubility of drugs and the molecular weight of the
      polymers. Generally, increased drug release rates were prevalent in soluble drug
      formulations (propranolol) when stored at the elevated temperature (40  degrees
      C). In contrast, it was not observed with semi soluble (theophylline) and poorly
      soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This
      indicates that the main parameters controlling the drug release from fresh polyox
      matrices are the solubility of the drug in the dissolution medium and the
      molecular weight of the polymer. DSC traces indicated that that there was a big
      difference in the enthalpy and melting points of fresh and aged PEO samples
      containing propranolol, whereas the melting point of the aged polyox samples
      containing theophylline and zonisamide was unaffected. Graphical abstract ?.

PMID- 27873082
TI  - I Can See Clearly Now: Using Active Visualisation to Improve Adherence to ART and
      PrEP.
AB  - Non-adherence remains a perplexing issue in HIV treatment. After decades of
      research supporting the efficacy of antiretroviral therapy, non-adherence to
      medication remains an important issue. For patients who are non-adherent to anti
      retroviral therapy (ART), there appears to be a mismatch between their model of
      illness and the necessity for ART treatment. We propose that 'active
      visualisation' is a technique that could be utilised to improve understanding of
      treatment and subsequently adherence for both individuals living with HIV and
      those at-risk of infection. We discuss the theoretical background and highlight
      the initial evidence suggesting the utility of active visualisation. We then
      discuss how active visualisation could be utilised in a live demonstration to
      improve adherence to ART and pre-exposure prophylaxis medications.

PMID- 27873081
TI  - Awareness and Acceptability of Pre-exposure HIV Prophylaxis Among Men Who have
      Sex with Men in Baltimore.
AB  - This paper assessed characteristics associated with awareness of and willingness
      to take pre-exposure prophylaxis (PrEP) among Baltimore men who have sex with men
      (MSM). We used data from BESURE-MSM3, a venue-based cross-sectional HIV
      surveillance study conducted among MSM in 2011. Multivariate regression was used
      to identify characteristics associated with PrEP knowledge and acceptability
      among 399 participants. Eleven percent had heard of PrEP, 48% would be willing to
      use PrEP, and none had previously used it. In multivariable analysis, black race
      and perceived discrimination against those with HIV were significantly associated
      with decreased awareness, and those who perceived higher HIV discrimination
      reported higher acceptability of PrEP. Our findings indicate a need for further
      education about the potential utility of PrEP in addition to other prevention
      methods among MSM. HIV prevention efforts should address the link between
      discrimination and potential PrEP use, especially among men of color.

PMID- 27873079
TI  - Next generation predictive biomarkers for immune checkpoint inhibition.
AB  - With the advent of targeted therapies, there has been a revolution in the
      treatment of cancer across multiple histologies. Immune checkpoint blockade has
      made it possible to take advantage of receptor-ligand interactions between immune
      and tumor cells in a wide spectrum of malignancies. Toxicity in healthy tissue,
      however, can limit our use of these agents. Immune checkpoint blockade has been
      approved in advanced melanoma, renal cell cancer, non-small cell lung cancer,
      relapsed refractory Hodgkin's lymphoma, and urothelial cancer. Though FDA
      approved indications for use of some of these novel agents depend on current
      protein-based programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1)
      assays, detection methods come with several caveats. Additional predictive tools
      must be interrogated to discern responders from non-responders. Some of these
      include measurement of microsatellite instability, PD-L1 amplification, cluster
      of differentiation 8 (CD8) infiltrate density, and tumor mutational burden. This
      review serves to synthesize biomarker detection at the DNA, RNA, and protein
      level to more accurately forecast benefit from these novel agents.

PMID- 27873083
TI  - The Cost and Threshold Analysis of Retention in Care (RiC): A Multi-Site National
      HIV Care Program.
AB  - Persons diagnosed with HIV but not retained in HIV medical care accounted for the
      majority of HIV transmissions in 2009 in the United States (US). There is an
      urgent need to implement and disseminate HIV retention in care programs; however
      little is known about the costs associated with implementing retention in care
      programs. We assessed the costs and cost-saving thresholds for seven Retention in
      Care (RiC) programs implemented in the US using standard methods recommended by
      the US Panel on Cost-effectiveness in Health and Medicine. Data were gathered
      from accounting and program implementation records, entered into a standardized
      RiC economic analysis spreadsheet, and standardized to a 12 month time frame.
      Total program costs for from the societal perspective ranged from $47,919 to
      $423,913 per year or $146 to $2,752 per participant. Cost-saving thresholds
      ranged from 0.13 HIV transmissions averted to 1.18 HIV transmission averted per
      year. We estimated that these cost-saving thresholds could be achieved through 1
      to 16 additional person-years of viral suppression. Across a range of program
      models, retention in care interventions had highly achievable cost-saving
      thresholds, suggesting that retention in care programs are a judicious use of
      resources.

PMID- 27873086
TI  - What We Know and Do Not Know About Actin.
AB  - Seven decades of research have revealed much about actin structure, assembly,
      regulatory proteins, and cellular functions. However, some key information is
      still missing, so we do not understand the mechanisms of most processes that
      depend on actin. This chapter summarizes our current knowledge and explains some
      examples of work that will be required to fill these gaps and arrive at a
      mechanistic understanding of actin biology.

PMID- 27873084
TI  - Distortion-Product Otoacoustic Emission Measured Below 300 Hz in Normal-Hearing
      Human Subjects.
AB  - Physiological noise levels in the human ear canal often exceed naturally low
      levels of otoacoustic emissions (OAEs) near the threshold of hearing. Low
      frequency noise, and electronic filtering to cope with it, has effectively
      limited the study of OAE to frequencies above about 500 Hz. Presently, a custom
      built low-frequency acoustic probe was put to use in 21 normal-hearing human
      subjects (of 34 recruited). Distortion-product otoacoustic emission (DPOAE) was
      measured in the enclosed ear canal volume as the response to two simultaneously
      presented tones with frequencies f 1 and f 2. The stimulus-frequency ratio f 2/f
      1 was varied systematically to find the "optimal" ratio evoking the largest level
      at 2 f 1-f 2 frequencies 87.9, 176, and 264 Hz. No reference data exist in this
      frequency region. Results show that DPOAE exists down to at least 87.9 Hz,
      maintaining the bell-shaped dependence on the f 2/f 1 ratio known from higher
      frequencies. Toward low frequencies, however, the bell broadens and the optimal
      ratio increases proportionally to the bandwidth of an auditory filter as defined
      by the equivalent rectangular bandwidth. The DPOAE phase rotates monotonously as
      a function of the stimulus ratio, and its slope trend supports the notion of a
      lack of scaling symmetry in the apex of the cochlea.

PMID- 27873085
TI  - Quantitative Analysis of Supporting Cell Subtype Labeling Among CreER Lines in
      the Neonatal Mouse Cochlea.
AB  - Four CreER lines that are commonly used in the auditory field to label cochlear
      supporting cells (SCs) are expressed in multiple SC subtypes, with some lines
      also showing reporter expression in hair cells (HCs). We hypothesized that
      altering the tamoxifen dose would modify CreER expression and target subsets of
      SCs. We also used two different reporter lines, ROSA26 tdTomato and CAG-eGFP, to
      achieve the same goal. Our results confirm previous reports that Sox2 CreERT2 and
      Fgfr3-iCreER T2 are not only expressed in neonatal SCs but also in HCs.
      Decreasing the tamoxifen dose did not reduce HC expression for Sox2 CreERT2 , but
      changing to the CAG-eGFP reporter decreased reporter-positive HCs sevenfold.
      However, there was also a significant decrease in the number of reporter-positive
      SCs. In contrast, there was a large reduction in reporter-positive HCs in Fgfr3
      iCreER T2 mice with the lowest tamoxifen dose tested yet only limited reduction
      in SC labeling. The targeting of reporter expression to inner phalangeal and
      border cells was increased when Plp-CreER T2 was paired with the CAG-eGFP
      reporter; however, the total number of labeled cells decreased. Changes to the
      tamoxifen dose or reporter line with Prox1 CreERT2 caused minimal changes. Our
      data demonstrate that modifications to the tamoxifen dose or the use of different
      reporter lines may be successful in narrowing the numbers and/or types of cells
      labeled, but each CreER line responded differently. When the ROSA26 tdTomato
      reporter was combined with any of the four CreER lines, there was no difference
      in the number of tdTomato-positive cells after one or two injections of tamoxifen
      given at birth. Thus, tamoxifen-mediated toxicity could be reduced by only giving
      one injection. While the CAG-eGFP reporter consistently labeled fewer cells, both
      reporter lines are valuable depending on the goal of the study.

PMID- 27873087
TI  - Key Questions for Translation of FFA Receptors: From Pharmacology to Medicines.
AB  - The identification of fatty acids as ligands for the G-protein coupled free fatty
      acid (FFA) receptor family over 10 years ago led to intensive chemistry efforts
      to find small-molecule ligands for this class of receptors. Identification of
      potent, selective modulators of the FFA receptors and their utility in medicine
      has proven challenging, in part due to their complex pharmacology. Nevertheless,
      ligands have been identified that are sufficient for exploring the therapeutic
      potential of this class of receptors in rodents and, in the case of FFA1, FFA2,
      FFA4, and GPR84, also in humans. Expression profiling, the phenotyping of FFA
      receptor knockout mice, and the results of studies exploring the effects of these
      ligands in rodents have uncovered a number of indications where engagement of one
      or a combination of FFA receptors might provide some clinical benefit in areas
      including diabetes, inflammatory bowel syndrome, Alzheimer's, pain, and cancer.
      In this chapter, we will review the clinical potential of modulating FFA
      receptors based on preclinical and in some cases clinical studies with synthetic
      ligands. In particular, key aspects and challenges associated with small-molecule
      ligand identification and FFA receptor pharmacology will be addressed with a view
      of the hurdles that need to be overcome to fully understand the potential of the
      receptors as therapeutic targets.

PMID- 27873088
TI  - Anti-Inflammatory and Insulin-Sensitizing Effects of Free Fatty Acid Receptors.
AB  - Chronic low-grade inflammation in macrophages and adipose tissues can promote the
      development of obesity and type 2 diabetes. Free fatty acids (FFAs) have
      important roles in various tissues, acting as both essential energy sources and
      signaling molecules. FFA receptors (FFARs) can modulate inflammation in various
      types of cells and tissues; however the underlying mechanisms mediating these
      effects are unclear. FFARs are activated by specific FFAs; for example, GPR40 and
      GPR120 are activated by medium and long chain FFAs, GPR41 and GPR43 are activated
      by short chain FFAs, and GPR84 is activated by medium-chain FFAs. To date, a
      number of studies associated with the physiological functions of G protein
      coupled receptors (GPCRs) have reported that these GPCRs are expressed in various
      tissues and involved in inflammatory and metabolic responses. Thus, the
      development of selective agonists or antagonists for various GPCRs may facilitate
      the establishment of novel therapies for the treatment of various diseases. In
      this review, we summarize current literature describing the potential of GPCRs as
      therapeutic targets for inflammatory and metabolic disorders.

PMID- 27873089
TI  - Gut Hormone Regulation and Secretion via FFA1 and FFA4.
AB  - The digestion, absorption and utilisation of dietary triglycerides are controlled
      by gut hormones, released from enteroendocrine cells along the length of the
      gastrointestinal tract. Major players in the detection of ingested lipids are the
      free fatty acid receptors FFA1 and FFA4, which are highly expressed on
      enteroendocrine cells. These receptors are activated when free fatty acids (FFA)
      are absorbed across the intestinal epithelium, and provide a dynamic hormonal
      signal indicating that lipids are arriving in the bloodstream from the gut. This
      review addresses our current knowledge of how ingested triglycerides modulate gut
      hormone release via FFA1 and FFA4.

PMID- 27873090
TI  - Evaluating the Psychometric Properties of the Eating Assessment Tool (EAT-10)
      Using Rasch Analysis.
AB  - Early and reliable screening for oropharyngeal dysphagia (OD) symptoms in at-risk
      populations is important and a crucial first stage in effective OD management.
      The Eating Assessment Tool (EAT-10) is a commonly utilized screening and outcome
      measure. To date, studies using classic test theory methodologies report good
      psychometric properties, but the EAT-10 has not been evaluated using item
      response theory (e.g., Rasch analysis). The aim of this multisite study was to
      evaluate the internal consistency and structural validity and conduct a
      preliminary investigation of the cross-cultural validity of the EAT-10; floor and
      ceiling effects were also checked. Participants involved 636 patients deemed at
      risk of OD, from outpatient clinics in Spain, Turkey, Sweden, and Italy. The EAT
      10 and videofluoroscopic and/or fiberoptic endoscopic evaluation of swallowing
      were used to confirm OD diagnosis. Patients with esophageal dysphagia were
      excluded to ensure a homogenous sample. Rasch analysis was used to investigate
      person and item fit statistics, response scale, dimensionality of the scale,
      differential item functioning (DIF), and floor and ceiling effect. The results
      indicate that the EAT-10 has significant weaknesses in structural validity and
      internal consistency. There are both item redundancy and lack of easy and
      difficult items. The thresholds of the rating scale categories were disordered
      and gender, confirmed OD, and language, and comorbid diagnosis showed DIF on a
      number of items. DIF analysis of language showed preliminary evidence of problems
      with cross-cultural validation, and the measure showed a clear floor effect. The
      authors recommend redevelopment of the EAT-10 using Rasch analysis.

PMID- 27873092
TI  - Molecular high-order harmonic spectra and its application to the generation of
      the isolated attosecond pulse.
AB  - Molecular high-order harmonic generation (HHG) spectra from H2+ and its
      application to the generation of the isolated attosecond pulses (IAPs) have been
      numerically investigated. Results show that (i) the 7th harmonic order is
      enhanced with the nuclei around the equilibrium internuclear, and as the
      internuclear distance increased, this enhanced harmonic produces a red-shift
      (even disappearance). Theoretical analyses show that the electronic transition
      between the ground and the 1st excited states is responsible for the red-shift
      enhanced harmonic. (ii) The harmonic spectra exhibit several maxima and minima,
      and a red-shift of these points is predicted as the internuclear distance
      increased. (iii) By properly choosing the internuclear distance, the harmonic
      yield is enhanced, and there is only the single quantum path contributing to the
      harmonic spectra. (iv) Further, by properly adding the half-cycle pulse as well
      as the spatial inhomogeneous effect, a 375 eV supercontinuum with a pulse
      enhancement of 3.9 dB and some attosecond X-ray pulses shorter than 60as can be
      produced.

PMID- 27873091
TI  - Pre-pharyngeal Swallow Effects of Recurrent Laryngeal Nerve Lesion on Bolus Shape
      and Airway Protection in an Infant Pig Model.
AB  - Recurrent laryngeal nerve (RLN) damage in infants leads to increased dysphagia
      and aspiration pneumonia. Recent work has shown that intraoral transport and
      swallow kinematics change following RLN lesion, suggesting potential changes in
      bolus formation prior to the swallow. In this study, we used geometric
      morphometrics to understand the effect of bolus shape on penetration and
      aspiration in infants with and without RLN lesion. We hypothesized (1) that
      geometric bolus properties are related to airway protection outcomes and (2) that
      in infants with RLN lesion, the relationship between geometric bolus properties
      and dysphagia is changed. In five infant pigs, dysphagia in 188 swallows was
      assessed using the Infant Mammalian Penetration-Aspiration Scale (IMPAS). Using
      images from high-speed VFSS, bolus shape, bolus area, and tongue outline were
      quantified digitally. Bolus shape was analyzed using elliptical Fourier analysis,
      and tongue outline using polynomial curve fitting. Despite large inter-individual
      differences, significant within individual effects of bolus shape and bolus area
      on airway protection exist. The relationship between penetration-aspiration score
      and both bolus area and shape changed post lesion. Tongue shape differed between
      pre- and post-lesion swallows, and between swallows with different IMPAS scores.
      Bolus shape and area affect airway protection outcomes. RLN lesion changes that
      relationship, indicating that proper bolus formation and control by the tongue
      require intact laryngeal sensation. The impact of RLN lesion on dysphagia is
      pervasive.

PMID- 27873093
TI  - Fatty acids in a high-fat diet potentially induce gastric parietal-cell damage
      and metaplasia in mice.
AB  - BACKGROUND: Obesity is associated with risk of adenocarcinoma in the proximal
      stomach. We aimed to identify the links between dietary fat and gastric
      premalignant lesions. METHODS: C57BL/6 mice were fed high fat diet (HFD), and
      gastric mucosa was histologically analysed. Morphological changes were also
      analysed using an electron microscope. Transcriptome analysis of purified
      parietal cells was performed, and non-parietal gastric corpus epithelial cells
      were subjected to single-cell gene-expression profiling. Composition of gastric
      contents of HFD-fed mice was compared with that of the HFD itself. Lipotoxicity
      of free fatty acids (FFA) was examined in primary culture and organoid culture of
      mouse gastric epithelial cells in vitro, as well as in vivo, feeding FFA-rich
      diets. RESULTS: During ~8-20 weeks of HFD feeding, the parietal cells of the
      stomach displayed mitochondrial damage, and a total of 23% of the mice developed
      macroscopically distinct metaplastic lesions in the gastric corpus mucosa.
      Transcriptome analysis of parietal cells indicated that feeding HFD enhanced
      pathways related to cell death. Histological analysis and gene-expression
      profiling indicated that the lesions were similar to previously reported
      precancerous lesions identified as spasmolytic polypeptide-expressing metaplasia.
      FFAs, including linoleic acid with refluxed bile acids were detected in the
      stomachs of the HFD-fed mice. In vitro, FFAs impaired mitochondrial function and
      decreased the viability of parietal cells. In vivo, linoleic acid-rich diet, but
      not stearic acid-rich diet induced parietal-cell loss and metaplastic changes in
      mice. CONCLUSIONS: Dietary lipids induce parietal-cell damage and may lead to the
      development of precancerous metaplasia.

PMID- 27873097
TI  - CORR Insights(r): A Crosswalk Between UCLA and Lower Extremity Activity Scales.

PMID- 27873098
TI  - On Patient Safety: Being a Jerk in the Operating Room is Bad for the Patient.

PMID- 27873094
TI  - The combination of elbasvir and grazoprevir for the treatment of chronic HCV
      infection in Japanese patients: a randomized phase II/III study.
AB  - BACKGROUND: Elbasvir (EBR) in combination with grazoprevir (GZR) has demonstrated
      efficacy in patients with hepatitis C virus (HCV) infections in trials primarily
      conducted in the USA and Europe. We investigated the safety and efficacy of EBR
      in combination with GZR in Japanese patients with chronic HCV infection, with or
      without cirrhosis. METHODS: The study was conducted in two parts. In part 1,
      noncirrhotic patients were randomized 1:1 to receive EBR (50 mg) in combination
      with GZR (50 or 100 mg) once daily for 12 weeks. In part 2, noncirrhotic patients
      were randomized 3:1 to receive immediate or deferred treatment with EBR (50 mg)
      and GZR (100 mg, determined in part 1) for 12 weeks; cirrhotic patients received
      open-label immediate treatment. The primary efficacy end point was the rate of
      sustained virologic response 12 weeks after completion of the study treatment.
      RESULTS: In part 1, 63 patients were randomized to receive EBR in combination
      with GZR at a dose of 50 mg (n = 31) or 100 mg (n = 32). The SVR12 rates were
      100% with GZR at a dose of 50 mg and 96.8% with GZR at a dose of 100 mg.
      Tolerability was similar in both arms. In part 2, 301 noncirrhotic patients were
      randomized to receive immediate treatment (n = 227) or deferred treatment (n =
      74), and 35 cirrhotic patients were enrolled. The SVR12 rates were 96.5% and
      97.1% after immediate treatment in noncirrhotic and cirrhotic patients
      respectively. Safety was generally similar between immediate and deferred
      treatment. CONCLUSION: Treatment with EBR in combination with GZR for 12 weeks is
      effective and well tolerated in Japanese patients with chronic HCV infection.
      CLINICALTRIALS. GOV IDENTIFIER: NCT02203149.

PMID- 27873095
TI  - Oral branched-chain amino acid granules improve structure and function of human
      serum albumin in cirrhotic patients.
AB  - BACKGROUND AND AIMS: The aim of this study was to evaluate structural and
      functional alterations of human serum albumin (HSA), with a special focus on the
      oxidized and reduced forms, in patients with chronic liver disease. We also
      investigated whether oral branched-chain amino acid (BCAA) supplementation could
      induce structural changes and improve the functions of HSA. METHODS: The
      proportion of reduced and oxidized HSA was determined in 16 healthy controls and
      in 20 chronic hepatitis and 100 cirrhotic patients with stable conditions. To
      evaluate the functional properties of HSA, this study focused on the antioxidant
      and binding functions. The radical scavenging activity and binding ability of
      purified HSA were measured in 68 participants. After BCAA administration for 6
      months, 29 patients were evaluated for HSA structural changes, with 19 out of the
      29 patients also analyzed for HSA functional changes. RESULTS: There was a
      significant decrease in the amounts of reduced HSA in conjunction with liver
      disease progression. Receiver operating characteristic curve analysis
      demonstrated that the levels of reduced HSA had high accuracy in determining
      disease progression. Functional alterations were strongly correlated to the
      levels of reduced HSA. BCAA supplementation led to substantial increases in the
      amount of reduced HSA. The altered HSA was able to scavenge significantly more
      radicals and restore the binding ability. CONCLUSION: This study describes
      structural alterations and functional disturbances of HSA in patients with
      chronic liver disease, and indicates that the levels of reduced HSA might reflect
      disease progression and the functional properties of HSA. Moreover, oral BCAA
      supplementation increases the amount of reduced HSA, thereby leading to the
      restoration of HSA function in cirrhotic patients.

PMID- 27873096
TI  - [Experience in measuring the quality of treatment in interventional pain therapy
      : The Activity Index on a touchscreen PC].
AB  - BACKGROUND: There is a growing interest in patient-related outcome measurement.
      In this field questionnaires on touch screens are becoming more common. This
      study was designed to identify problems in usability and feasibility of a web
      based questionnaire. STUDY PARTICIPANTS AND METHODS: Patients who underwent a
      lumbar infiltration were recruited in 5 centers and 50 patients participated of
      which half were older than 62 years. One third of the patients had basically no
      former experience with computers or touch screens. The outcome was assessed
      before treatment and during follow-up on a simple web-based patient
      questionnaire, the Activity Index. Results were presented graphically and
      discussed during consultation. Patients, nurses and doctors were asked for
      standardized feedback. RESULTS: Of the patients 84% completed the questionnaire
      in up to 6 min. An adapted form of the system usability scale (SUS) achieved an
      acceptance score of 71.8%. Problems in handling occurred mostly in older patients
      (>65 years). The system was scored with 72.9% and 78.5% in efficiency and
      handling, respectively, by the nurses. The attending physicians rated the
      usefulness and comprehensibility of the graphical representation of the results
      on average as 83.3% and both were scored neutral to positive; however, an average
      of 11.6% rated some aspects of the report to be suboptimal. CONCLUSION: This web
      based questionnaire is the first of its kind to be evaluated in everyday practice
      of interventional pain therapy for lumbar back pain. The vast majority of the
      patients were able to efficiently complete the questionnaire. The questionnaire
      was highly acceptable to patients, nurses and doctors. We found some usability
      problems but mainly in the older age group.

PMID- 27873099
TI  - Metastasis to the Thyroid Gland: A Critical Review.
AB  - BACKGROUND: Metastasis to the thyroid gland from nonthyroid sites is an uncommon
      clinical presentation in surgical practice. The aim of this review was to assess
      its incidence management and outcomes. METHODS: A literature review was performed
      to identify reports of metastases to the thyroid gland. Both clinical and autopsy
      series were included. RESULTS: Metastases to the gland may be discovered at the
      time of diagnosis of the primary tumor, after preoperative investigation of a
      neck mass, or on histologic examination of a thyroidectomy specimen. The most
      common primary tumors in autopsy studies are from the lung. In clinical series,
      renal cell carcinoma is most common. For patients with widespread metastases in
      the setting of an aggressive malignancy, surgery is rarely indicated. However,
      when patients present with an isolated metastasis diagnosed during follow-up of
      indolent disease, surgery may achieve control of the central neck and even long
      term cure. Other prognosticators include features of the primary tumor, time
      interval between initial diagnosis and metastasis, and extrathyroid extent of
      disease. CONCLUSIONS: In patients with thyroid metastases, communication among
      clinicians treating the thyroid and the index primary tumor is essential. The
      setting is complex, and decisions must be made considering the features of the
      primary tumor, overall burden of metastases, and comorbidities. Careful balancing
      of these factors influences individualized approaches.

PMID- 27873101
TI  - Relationship between blood pressure and frailty in older hypertensive
      outpatients.
AB  - BACKGROUND: The benefits and risks of treating hypertension in old and frail
      patients are debated. AIM: The aim of the present study is to measure the frailty
      status in older patients with hypertension and determine the relationships
      existing between blood pressure (BP) values and frailty. METHODS: Frailty was
      retrospectively assessed by using the frailty index (FI) in 56 hypertensive old
      outpatients. Patients with an FI > 0.25 were classified as frail. RESULTS: Forty
      five out of 56 (80%) had a FI > 0.25. A statistically significant inverse
      correlation was found between FI and systolic BP (r = -0.319, p = 0.016),
      orthostatic systolic BP (r = -0.408, p = 0.002), orthostatic diastolic BP (r = 
      0.299, p = 0.025), and orthostatic pulse pressure (r = -0.297, p = 0.026).
      DISCUSSION: Frailer subjects appear as over-treated according to current European
      guidelines. CONCLUSIONS: FI can play an important role in the clinical setting by
      supporting the identification of subjects at risk and allowing an improved
      provision of adapted and personalized care.

PMID- 27873100
TI  - The Pretreatment Systemic Inflammatory Response is an Important Determinant of
      Poor Pathologic Response for Patients Undergoing Neoadjuvant Therapy for Rectal
      Cancer.
AB  - BACKGROUND: Not all patients respond equally to neoadjuvant chemoradiotherapy
      (nCRT), with subsequent effects on survival. The systemic inflammatory response
      has been shown to predict long-term outcomes in colorectal cancer. The current
      study examined the association between systemic inflammation and nCRT in patients
      with rectal cancer. METHODS: Between 1999 and 2010, patients who underwent nCRT
      were identified. Serum measurements of hemoglobin, C-reactive protein, albumin,
      modified Glasgow prognostic score (mGPS), and differential white cell counts were
      obtained before and after nCRT. The Rodel scoring system measured pathologic
      tumor regression, and magnetic resonance imaging and computed tomography
      determined radiologic staging. RESULTS: The study included 79 patients. Of these
      patients, 37% were radiologically downstaged, and 44% were categorized as showing
      a good pathologic response (Rodel scores 3 and 4). As a validated measure of the
      systemic inflammatory response, mGPS (P = 0.022) was associated with a poor
      pathologic response to nCRT. A radiologic response was associated with a good
      pathologic response to treatment (P = 0.003). A binary logistic regression model
      identified mGPS (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.07-0.96; P
      = 0.043) and radiologic response (OR 0.43; 95% CI 0.18-0.99; P = 0.048) as strong
      independent predictors of a pathologic response to treatment. CONCLUSION: The
      current study showed that a systemic inflammatory response before nCRT is
      associated with a poor pathologic response. Further study in a prospective
      controlled trial setting is warranted.

PMID- 27873102
TI  - Fine-needle cytology in the follow-up of breast carcinoma.
AB  - The postoperative follow-up strategies for breast carcinoma (BC) utilize
      different procedures; the aim of this study was to investigate the role of fine
      needle cytology (FNC) in the follow-up of BC patients. Two hundred sixty-six FNC
      samples from 190 BC patients have been reviewed. The target anatomical sites were
      190 breast including 155 ipsilateral and 145 contralateral breast lesions and 76
      extra-mammary nodules. Extra-mammary lesions included lymph nodes, thyroidal
      nodules, soft tissue lesions, (subcutaneous and sub-scars), salivary glands and
      deep located masses. Diagnostic distribution of the breast lesions was as
      follows: 51 positive, 15 indeterminate/suspicious, 119 negative and 5 inadequate.
      Positive cases included 43 ipsilateral and 8 contralateral BC, 9 BC in different
      quadrants from those of onset of the first BC. Sensitivity, specificity and
      accuracy have been 90, 91 and 90&, respectively. FNC, in a correct setting, is a
      reliable and effective method for the follow-up management of BC patients.

PMID- 27873103
TI  - Differential regulation of angiogenic cellular processes and claudin-5 by
      histamine and VEGF via PI3K-signaling, transcription factor SNAI2 and interleukin
      8.
AB  - AIMS: Histamine and vascular endothelial growth factor A (VEGF) are central
      regulators in vascular pathologies. Their gene regulation leading to vascular
      remodeling has remained obscure. In this study, EC regulation mechanisms of
      histamine and VEGF were compared by RNA sequencing of primary endothelial cells
      (ECs), functional in vitro assays and in vivo permeability mice model. METHODS
      AND RESULTS: By RNA sequencing, similar transcriptional alterations of genes
      involved in activation of primary ECs, cell proliferation and adhesion were
      observed between histamine and VEGF. Seventy-six commonly regulated genes were
      found, representing ~53% of all VEGF-regulated transcripts and ~26% of all
      histamine-regulated transcripts. Both factors regulated tight junction formation
      and expression of pro-angiogenic transcription factors (TFs) affecting EC
      survival, migration and tube formation. Novel claudin-5 upstream regulatory genes
      were identified. VEGF was demonstrated to regulate expression of SNAI2, whereas
      pro-angiogenic TFs NR4A1, MYCN and RCAN1 were regulated by both histamine and
      VEGF. Claudin-5 was shown to be regulated VEGFR2/PI3K-Akt dependently by VEGF and
      PI3K-Akt independently by histamine. Interleukin-8 was shown to downregulate
      claudin-5 by histamine. Additionally, SNAI2, NR4A1 and MYCN were shown to mediate
      EC survival, migration and tube formation and to regulate expression of claudin
      5. Further systemic delivery of VEGF and histamine was shown to induce a fast
      vascular hyperpermeability response in intact vasculature of C57/Bl6 mice
      followed by regulation of NR4A1 and MYCN. CONCLUSIONS: Our study identifies novel
      claudin-5 upstream regulatory genes of histamine and VEGF that induce cellular
      angiogenic processes. Our results increase knowledge of angiogenic EC phenotype
      and provide novel treatment targets for vascular pathologies.

PMID- 27873104
TI  - Analysis of specific absorption rate and internal electric field in human
      biological tissues surrounding an air-core coil-type transcutaneous energy
      transmission transformer.
AB  - In this study, we analyzed the internal electric field E and specific absorption
      rate (SAR) of human biological tissues surrounding an air-core coil
      transcutaneous energy transmission transformer. Using an electromagnetic
      simulator, we created a model of human biological tissues consisting of a dry
      skin, wet skin, fat, muscle, and cortical bone. A primary coil was placed on the
      surface of the skin, and a secondary coil was located subcutaneously inside the
      body. The E and SAR values for the model representing a 34-year-old male subject
      were analyzed using electrical frequencies of 0.3-1.5 MHz. The transmitting power
      was 15 W, and the load resistance was 38.4 Omega. The results showed that the E
      values were below the International Commission on Non-ionizing Radiation
      Protection (ICNIRP) limit for the general public exposure between the frequencies
      of 0.9 and 1.5 MHz, and SAR values were well below the limit prescribed by the
      ICNIRP for the general public exposure between the frequencies of 0.3 and 1.2
      MHz.

PMID- 27873105
TI  - Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden-a 2-Year
      Pilot TREC and KREC Screening Study.
AB  - Newborn screening for severe primary immunodeficiencies (PID), characterized by T
      and/or B cell lymphopenia, was carried out in a pilot program in the Stockholm
      County, Sweden, over a 2-year period, encompassing 58,834 children. T cell
      receptor excision circles (TREC) and kappa-deleting recombination excision
      circles (KREC) were measured simultaneously using a quantitative PCR-based method
      on DNA extracted from dried blood spots (DBS), with beta-actin serving as a
      quality control for DNA quantity. Diagnostic cutoff levels enabling
      identification of newborns with milder and reversible T and/or B cell lymphopenia
      were also evaluated. Sixty-four children were recalled for follow-up due to low
      TREC and/or KREC levels, and three patients with immunodeficiency (Artemis-SCID,
      ATM, and an as yet unclassified T cell lymphopenia/hypogammaglobulinemia) were
      identified. Of the positive samples, 24 were associated with prematurity.
      Thirteen children born to mothers treated with immunosuppressive agents during
      pregnancy (azathioprine (n = 9), mercaptopurine (n = 1), azathioprine and
      tacrolimus (n = 3)) showed low KREC levels at birth, which spontaneously
      normalized. Twenty-nine newborns had no apparent cause identified for their
      abnormal results, but normalized with time. Children with trisomy 21 (n = 43)
      showed a lower median number of both TREC (104 vs. 174 copies/MUL blood) and KREC
      (45 vs. 100 copies/3.2 mm blood spot), but only one, born prematurely, fell below
      the cutoff level. Two children diagnosed with DiGeorge syndrome were found to
      have low TREC levels, but these were still above the cutoff level. This is the
      first large-scale screening study with a simultaneous detection of both TREC and
      KREC, allowing identification of newborns with both T and B cell defects.

PMID- 27873106
TI  - Lack of Clinical Hypersensitivity to Penicillin Antibiotics in Common Variable
      Immunodeficiency.

PMID- 27873107
TI  - Assessment of potential impacts of climate change on agricultural development in
      the Lower Benue River Basin.
AB  - Agriculture in the Lower Benue River Basin faces several challenges which
      threaten the future of agricultural development. This study was an assessment of
      potential impacts of climate change on agricultural development in the Lower
      Benue River Basin. Through analysis of physical and socioeconomic parameters, the
      study adapted an impact assessment model to rank potential impacts on
      agricultural development in the study area. Rainfall intensity seemed to be
      increasing with a gradual reduction in the number of rainy days. The average
      discharge at Makurdi hydrological station was 3468.24 cubic metres per second (m3
      s-1), and the highest peak flow discharge was 16,400 m3 s-1. The daily maximum
      temperature and annual temperature averages for the study area are gradually
      rising leading to increased heat stress. Physical and chemical analyses showed
      that the soils are moderately fertile but require effective application of
      inorganic and organic fertilisers. The main occupational activities in the study
      area are agricultural based. The identified potential impacts of climate change
      on agriculture were categorised under atmospheric carbon dioxides and oxides,
      rainfall intensity, frequency of floods and droughts, temperature intensity and
      variation, heat stress, surface water trends, and soil quality and fertility. The
      identified potential impacts related to population dynamics on agriculture were
      categorised under population growth, rural-urban migration, household income and
      infectious diseases and HIV and AIDS. Community-level mitigation strategies were
      proffered. Policy makers are advised to promote irrigation farming, support
      farmers with farm inputs and credit facilities and establish active agricultural
      extension services to support the sustainable development of agriculture.

PMID- 27873108
TI  - Flushing in (neuro)endocrinology.
AB  - Cutaneous flushing is a common presenting complaint in endocrine disorders. The
      pathophysiology of flushing involves changes in cutaneous blood flow triggered by
      multiple intrinsic factors that are either related to physiology or disease.
      Flushing can be divided into episodic or persistent causes. Episodic flushing is
      mediated by the release of endogenous vasoactive mediators or medications, while
      persistent flushing results in a fixed facial erythema with telangiectasia and
      cyanosis due to slow-flowing deoxygenated blood in large cutaneous blood vessels.
      The differential diagnosis of cutaneous flushing in neuroendocrine disorders is
      limited, yet encompasses a broad spectrum of benign and malignant entities,
      including carcinoid syndrome, pheochromocytoma, Cushing syndrome, medullary
      thyroid cancer, and pancreatic neuroendocrine tumors. In this review, we provide
      a concise and up-to-date discussion on the differential diagnosis and approach of
      flushing in neuroendocrinology.

PMID- 27873109
TI  - Bioavailability and health risk assessment of potentially toxic elements in
      Thriasio Plain, near Athens, Greece.
AB  - Elevated concentrations of potentially toxic elements (PTEs) are usually found in
      areas of intense industrial activity. Thriasio Plain is a plain near Athens,
      Greece, where most of the heavy industry of the country has been situated for
      decades, but it also is a residential and horticultural area. We aimed at
      measuring the levels of PTEs in soils and indigenous plant species and assessing
      the health risk associated with direct soil ingestion. Samples of soils at
      roadsides and growing plants were collected from 31 sites of that area.
      Concentrations of Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, V and Zn were
      measured in both soils (as pseudo-total) and aerial plant tissues. We found that
      As, Cd, Cr, Cu, Ni, Pb and Zn were higher than maximum regulatory limits. Element
      concentrations in plants were rather lower than expected, probably because
      indigenous plants have developed excluder behaviour over time. Copper and Zn soil
      to-plant coefficients were highest among the other elements; for Cu this was
      unexpected, and probably associated with recent Cu-releasing industrial activity.
      Risk assessment analysis indicated that As was the element contributing more than
      50 % of the health risk related to direct soil ingestion, followed by Cr, Pb,
      and, surprisingly, Mn. We concluded that in a multi-element contamination
      situation, elevated risk of PTEs (such as As, Cr and Pb) may reduce the tolerance
      limits of exposure to less-toxic elements (here, Mn).

PMID- 27873110
TI  - Remediation of Cd(II)-contaminated soil via humin-enhanced electrokinetic
      technology.
AB  - Humin is the component of humic substances that is recalcitrant to extraction by
      either strong bases or strong acids, which contains a variety of functional
      groups that may combine with heavy metal ions. The present study employed humin
      as an adsorbent to investigate the efficacy of a remediation strategy under the
      effects of humin-enhanced electrokinetics. Because the cations gravitate toward
      cathode and anions are transferred to anode, humin was placed in close proximity
      to the cathode in the form of a package. The humin was taken out after the
      experiments to determine whether a target pollutant (cadmium) might be completely
      removed from soil. Acetic acid-sodium acetate was selected as the electrolyte for
      these experiments, which was circulated between the two electrode chambers via a
      peristaltic pump, in order to control the pH of the soil. The results indicated
      that when the remediation duration was extended to 240 h, the removal of acid
      extractable Cd(II) could be up to 43.86% efficiency, and the adsorption of the
      heavy metal within the humin was 86.15 mg/kg. Further, the recycling of the
      electrolyte exhibited a good control of the pH of the soil. When comparing the pH
      of the soil with the circulating electrolyte during remediation, in contrast to
      when it was not being recycled, the pH of the soil at the anode increased from
      3.89 to 5.63, whereas the soil at the cathode decreased from 8.06 to 7.10. This
      indicated that the electrolyte recycling had the capacity to stabilize the pH of
      the soil.

PMID- 27873111
TI  - Bioaugmentation of a continuous-flow self-forming dynamic membrane bioreactor for
      the treatment of wastewater containing high-strength pyridine.
AB  - For the treatment of high-strength pyridine containing wastewater, a bioaugmented
      continuous-flow self-forming dynamic membrane bioreactor (CSFDMBR), which was
      consisted of a continuous flow airlift reactor (CFAR) and a dynamic membrane
      bioreactor (DMBR), was developed in this study. The results indicated that
      through the bioaugmentation by Rhizobium sp. NJUST18, CSFDMBR could be
      successfully started, which was confirmed by complete removal of pyridine,
      efficient nitrification, and significant increase of biomass. Pyridine could be
      effectively degraded in the CSFDMBR even at influent pyridine loading rate as
      high as 9.0 kg m-3 day-1, probably due to the efficient biomass retention in the
      CSFDMBR, which could be attributed to the formation of aerobic granules and the
      key role of dynamic membrane. CSFDMBR presented good polishing performance in
      treating pyridine wastewater, with effluent total organic carbon (TOC) and
      turbidity as low as 22.5 +/- 6.8 mg L-1 and 3.8 +/- 0.5 NTU, respectively.
      Membrane fouling could be effectively controlled, as indicated by backwash period
      as long as 60 days. The observed efficient performance highlights the potential
      for the full-scale application of the bioaugmented CSFDMBR, particularly for
      highly recalcitrant pollutant removal.

PMID- 27873112
TI  - Influence of polymer composition on the sensitivity towards nitrite and nitric
      oxide of colorimetric disposable test strips.
AB  - The influence of polymer composition on the sensitivity towards nitrite (NO2-)
      and nitric oxide (NO) of a series of 19 polymeric hydrogel films has been
      studied. The polymers, based on the hydrophilic monomer 2
      hydroxyethylmethacrylate (HEMA), are able to encapsulate the colorimetric
      indicator 1,2-diaminoanthraquinone (DAQ) and to respond to NO2- and NO by visual
      changes. In the case of nitrite, the calculated limits of detection (LOD) for two
      of the polymeric sensors (10 MUM) are very close to the sensitivity estimated for
      free DAQ in solution (LOD 5 MUM), but with the advantage of a solid supported
      sensor with the format of a disposable test-strip made with affordable starting
      chemicals. The results are interpreted taking into account the nature and
      proportions of monomers and cross-linkers used for the synthesis of polymers. Key
      factors for obtaining sensitive materials are the hydrophilic character of the
      film along with the utilization of low levels of cross-linker and the use of an
      acidic monomer, like acrylic acid, as a building block.

PMID- 27873113
TI  - Low C/N ratio raw textile wastewater reduced labile C and enhanced organic
      inorganic N and enzymatic activities in a semiarid alkaline soil.
AB  - Application of raw and treated wastewater for irrigation is an extensive practice
      for agricultural production in arid and semiarid regions. Raw textile wastewater
      has been used for cultivation in urban and peri-urban areas in Pakistan without
      any systematic consideration to soil quality. We conducted a laboratory
      incubation study to investigate the effects of low C/N ratio raw textile
      wastewater on soil nitrogen (N) contents, labile carbon (C) as water-soluble C
      (WSC) contents, and activities of urease and dehydrogenase enzymes. The 60-day
      incubation study used an alkaline clay loam aridisol that received 0 (distilled
      water), 25, 50, and 100% wastewater concentrations, and microcosms were incubated
      aerobically under room temperature at 70% water holding capacity. Results
      revealed that raw wastewater significantly (p < 0.05) changed soil N pools and
      processes, WSC contents, and enzymatic activities. The organic and inorganic N
      species increased with increasing wastewater concentrations, whereas WSC contents
      followed an opposite trend. The highest NH4+-N and NO3--N contents were observed
      in soil treated with 100% wastewater. The extractable organic N (EON) contents
      always represented >50% of the soil total Kjeldahl N (TKN) contents and served as
      the major N pool. However, nitrification index (NO3--N/NH4+-N ratio) decreased at
      high wastewater concentrations. A significant negative correlation was observed
      between EON and WSC (p < 0.05) and between net nitrification and WSC/EON ratio (p
      < 0.01). In contrast, nitrification index and WSC contents were correlated,
      positively suggesting WSC potentially controlling N turnover in nutrient-poor
      aridisol. We found significant (p < 0.0001) positive correlations of soil urease
      and dehydrogenase enzymatic activities with soil-extractable mineral N contents
      indicating coupled N cycling and soil biological activity. Higher production and
      accumulation of soil NO3--N and EON contents in concentrated wastewater-treated
      soil could pose an ecological concern for soil fertility, biological health, and
      water quality. However, the EON could lead to mineral N pool but only if
      sufficient labile C source was present. The effects of wastewater irrigation on
      soil N cycling need to be assessed before it is recommended for crop production.

PMID- 27873115
TI  - Life cycle assessment of cheese production process in a small-sized dairy
      industry in Brazil.
AB  - Current research identifies, analyzes, and suggests improvements for minimizing
      environmental impacts in the manufacture of cheese using the life cycle
      assessment. Data collection and development of the inventory were performed in a
      small-sized dairy industry in Brazil. A cradle-to-gate approach was conducted
      based on the primary data from cheese production and secondary data from
      databases. The ReCiPe method was used for the impact assessment, considering the
      categories climate change, ozone depletion, terrestrial acidification, freshwater
      eutrophication, photochemical oxidant formation, particulate matter formation,
      water depletion, and fossil depletion. A sensitivity analysis was performed
      including evaluations of different fuels for generating thermal energy,
      strategies for cleaning of dairy plant and utensils, variations in the way of
      cheese production based on the fat content, and production percentage changes.
      The results showed that the skimmed milk and thermal energy productions,
      electricity usage, and water consumptions were the main elementary flows. The
      pallet residues showed the best to be used as fuel for thermal energy. Detergent
      combinations did not influence the impact categories. There was a direct
      relationship between fat content range (20 to 30%) and the contribution in six
      impact categories. Changes from 20% in cheese allocation factor influenced the
      impact assessment results. LCA allowed identifying the main elementary flow of
      cheese production, providing valuable information with the potential to verify
      opportunities for on-site improvements.

PMID- 27873114
TI  - Dissipation of antibiotics in three different agricultural soils after repeated
      application of biosolids.
AB  - Application of biosolids to agricultural soils is one of the pathways by which
      antibiotics can be introduced into agricultural ecosystems. A pot experiment was
      conducted with repeated soil amendment with biosolids to examine the
      concentrations of four classes of antibiotics (tetracyclines, sulfonamides,
      fluoroquinolones, and macrolides) and their dissipation in three different soil
      types in wheat-rice rotations. Antibiotics accumulate in the soils after repeated
      application of biosolids. Fluoroquinolones showed stronger accumulation and
      persistence in the test soils than the other three classes of antibiotics. The
      maximum residual antibiotic concentration was that of norfloxacin at 155 +/- 16
      MUg kg-1 in the Typic Hapli-Stagnic Anthrosols (paddy soil). Predicted half-lives
      were up to 3.69 years, a much longer period than that between biosolid
      applications (twice each year on average). Antibiotic accumulation followed the
      rough order fluoroquinolones > tetracyclines > macrolides > sulfonamides, and the
      sulfonamides were seldom encountered. When biosolid application was suspended,
      the dissipation rate accelerated. Antibiotic dissipation was slightly slower when
      biosolids with high heavy metal concentrations were applied and microbial
      degradation may have been the main mechanism of dissipation. Norfloxacin
      persistence was positively correlated with its soil adsorption capacity. Cation
      exchange capacity and soil organic matter content may have vital roles in the
      soil adsorption of fluoroquinolones. Because of their persistence, the
      fluoroquinolones must be taken into account in the planning of biosolid
      applications in agricultural practice.

PMID- 27873116
TI  - High added-value products from the hydrothermal carbonisation of olive stones.
AB  - Olive stones (OS) were submitted to hydrothermal carbonisation (HTC) in order to
      evaluate the possibility of producing high added-value products, mainly furfural
      (FU) and 5-hydroxymethylfurfural (5-HMF) on one hand and hydrochars and carbons
      on the other hand. Temperature (160-240  degrees C), residence time (1-8 h),
      initial pH (1-5.5) and liquid/solid ratio (4-48 w/w) were systematically varied
      in order to study the main products and to optimise FU production. FU production
      yield up to 19.9 %, based on the hemicellulose content, was obtained. Other
      minor, but valuable, compounds such as 5-methylfurfural (5-MF) and some phenolic
      compounds were also produced. The hydrochar was carbonised at 900  degrees C, and
      the resultant carbon material was highly ultramicroporous with a peak of pore
      size distribution centred on 0.5 nm and a surface area as high as 1065 m2 g-1,
      typical of most carbon molecular sieves.

PMID- 27873117
TI  - Mitigation of Pre-existing Antibodies to a Biotherapeutic in Non-clinical Species
      When Establishing Anti-drug Antibody Assay Cutpoint.
AB  - Biotherapeutics are known for their potential to induce drug specific immune
      responses, which are commonly evaluated by the detection of anti-drug antibodies
      (ADAs). For some biotherapeutics, pre-existing ADAs against drug have been
      observed in drug-naive matrix. The presence of pre-existing drug specific
      antibodies may significantly complicate assessment of the screening ADA assay
      cutpoint value, which is usually established based on the statistical analysis of
      signal distribution from the drug-naive individuals. A Gaussian mixture model
      based approach is presented herein to address high prevalence of pre-existing
      ADAs to a modified monoclonal antibody-based biotherapeutic (m-mAb). A high
      prevalence of pre-existing anti-m-mAb antibodies was observed in drug-naive
      individual cynomolgus monkey serum samples with signal ranging from 100 to 7000
      relative light units (RLU, as determined in an electrochemiluminescence readout
      based assay). Application of the industry standard statistical algorithm resulted
      in a relatively high floating screening assay cutpoint factor (CPF) of 9.80,
      which potentially would have reported a high percent of false negative samples.
      An alternative, Gaussian mixture model-based approach was applied to identify the
      least reactive individual samples in the tested population, which resulted in a
      floating screening assay CPF of 2.35. The low CPF value significantly reduced the
      risk of reporting false negative results. The proposed Gaussian mixture model
      based approach described herein provides an alternate method for the calculation
      of biologically relevant screening assay CPF when high prevalence of pre-existing
      drug specific antibodies is observed.

PMID- 27873119
TI  - Validation of a Drug-Resistant Anti-Adalimumab Antibody Assay to Monitor
      Immunogenicity in the Presence of High Concentrations of Adalimumab.
AB  - With respect to patient safety and long-term efficacy, immunogenicity of
      therapeutic antibodies remains an important issue. Pre-treatment of samples using
      either higher temperature or acidification in order to separate drug/anti-drug
      antibody complexes has been implemented in the traditional bridging assay and an
      in-house-developed affinity capture elution assay but only a limited drug
      tolerance was obtained. In this study, we aim to apply a drug-resistant anti-drug
      antibody assay to adalimumab through a combination of adalimumab/anti-adalimumab
      antibody complex precipitation and acid dissociation. A linear dose-response
      curve ranging from 3.1 to 200 ng/mL was obtained in 1/125 diluted serum, allowing
      detection of anti-adalimumab antibody concentrations up to 25 MUg/mL equivalents
      MA-ADM6A10, a calibrator anti-adalimumab antibody. The cut-off point for
      detection was determined using 16 samples of adalimumab naive patients and set at
      0.39 MUg/mL equivalents. Validation of the assay revealed that no detectable anti
      adalimumab antibody concentrations were found in samples with either a positive
      anti-infliximab antibody concentration, a physiologic concentration of TNFalpha,
      or a high concentration of rheumatoid factor. Full recoveries were obtained when
      various concentrations of adalimumab (0, 1, 10, and 50 MUg/mL) were spiked to 1,
      2, and 4 MUg/mL of MA-ADM6A10. Spiking of 50 MUg/mL adalimumab to eight
      individual sera revealed similar anti-adalimumab antibody concentrations as in
      the absence of adalimumab, with a Pearson r correlation of 0.99 and an interclass
      correlation of 0.99. The assay allows accurate evaluation of adalimumab
      immunogenicity during induction or upon dose intensification and in serum samples
      not taken at trough.

PMID- 27873118
TI  - Current Update of a Carboxymethylcellulose-PEG Conjugate Platform for Delivery of
      Insoluble Cytotoxic Agents to Tumors.
AB  - Cytotoxic chemotherapeutic agents are used as the standard therapy for a range of
      significant cancers, but many of these drugs suffer from poor water solubility
      and low selectivity, limiting their clinical efficacy. To overcome these
      shortcomings, CellaxTM drug delivery platform was developed. CellaxTM is a
      polymer-based nanoparticle drug delivery system designed to solubilize
      hydrophobic drugs and target them to solid tumors, thereby enhancing the efficacy
      and reducing the side effects. Cellax-docetaxel (Cellax-DTX) displayed improved
      pharmacokinetic, safety, and efficacy profiles compared to native DTX
      (Taxotere(r)) and Nab-paclitaxel (Nab-PTX, Abraxane(r)) in multiple animal
      models. Cellax-DTX was shown to interact with serum albumin and SPARC (secreted
      protein acidic and rich in cysteine) that is highly expressed by tumor stromal
      cells, leading to superior stroma depleting activity in orthotopic breast and
      pancreatic tumor models and subsequently reduced incidence of visceral metastases
      compared to free DTX and Nab-PTX. The CellaxTM platform was employed to deliver
      podophyllotoxin (Cellax-PPT) and cabazitaxel (Cellax-CBZ), and increased their
      safety and efficacy against multidrug-resistant tumors. This review discusses the
      rational design of the CellaxTM platform and summarizes the preclinical results.
      A multifunctional version of CellaxTM and a biomarker for predicting CellaxTM
      efficacy were developed and identified to promote the personalized use.
      Perspectives and future plans for this platform technology are also provided.

PMID- 27873120
TI  - "Katakori": a Pain Syndrome Specific to the Japanese.

PMID- 27873121
TI  - Challenges to Treatment of Chronic Pain and Addiction During the "Opioid Crisis".
AB  - Health care in the USA faces a double challenge, the crisis of chronic pain and
      the crisis of opioid misuse and overdose. Patients have been prescribed opioids
      at high doses with unclear indications for long periods of time, putting them at
      high risk for morbidity and mortality. A significant proportion of these patients
      have comorbid psychiatric or substance use disorders complicating their pain
      conditions. The challenges to treating these patients adequately are discussed,
      along with potential solutions to these issues at the level of the individual
      provider, healthcare systems, and society.

PMID- 27873122
TI  - How Well Does the ICHD 3 (Beta) Help in Real-Life Migraine Diagnosis and
      Management?
AB  - Classification has played a major role in the diagnosis of primary headache
      conditions including migraine with and without aura. With many updates and
      changes, the International Classification of Headache Disorders (ICHD)-3 beta is
      currently considered as the gold standard for classification of migraine and
      other headaches. Correct diagnosis of migraine and its subtypes is a first step
      toward appropriate treatment and crucial to minimizing disability and optimizing
      health-related quality of life. The ICHD-3 beta version represents the state of
      the art in migraine diagnosis but is expected to evolve as biological knowledge
      advances. Future research should focus on identification of biologically
      homogeneous subgroups of migraine based on genes and biomarkers.

PMID- 27873124
TI  - Carotid and Vertebral Dissection Imaging.
AB  - Carotid or vertebral artery dissection is the result of a tear in the vessel
      lining wherein the intima separates the media. This creates a false or pseudo
      lumen, often accompanied by hemorrhage into the arterial wall. Dissection of
      these craniocervical vessels often manifests with pain alone but, if untreated,
      may result in severe neurologic compromise. The causes of dissection are
      multifactorial, including spontaneous, iatrogenic, and traumatic insults.
      Regardless of etiology, treatment consists primarily of anticoagulation, whereas
      endovascular therapy is reserved for cases with persistent thrombus or flow
      limitation. Given the high risk of neurological compromise or death and the
      propensity of these injuries to occur in younger individuals, early diagnosis of
      carotid and vertebral artery dissections is critical. Although angiography
      remains the criterion standard for diagnosis, advances in noninvasive imaging
      have placed magnetic resonance and computed tomography at the forefront of
      diagnosis. This article examines the current imaging modalities used to diagnose
      this under-recognized entity.

PMID- 27873123
TI  - Vestibular Migraine in Children and Adolescents.
AB  - PURPOSE OF REVIEW: The goal of this review is to provide an actualized overview
      on vestibular migraine in childhood and adolescence, with focus on the
      epidemiology and clinical presentation as well as its treatment. RECENT FINDINGS:
      Vertigo spells in childhood can evolve into other periodic syndromes and/or
      migraine types and persist even into adulthood. Vestibular migraine (VM) and
      benign paroxysmal vertigo are the most common causes of vertigo in children and
      adolescents. The diagnostic criteria for VM are dizziness and vertigo, headache,
      phonophobia and photophobia, and visual aura. The prevention of attacks is the
      treatment for children and adolescents with VM, as is recommended for migraine
      with or without aura. Thus, non-pharmacological measures are the first-line
      option; when these measures fail or daily activities are notably affected, drugs
      are administrated. Psychological assessment and cognitive behavioral therapy are
      also important therapeutic measures in this patient group. There is still
      insufficient research on VM in children and adolescents; future studies on
      clinical presentation, evolvement, and specific treatment are necessary.

PMID- 27873126
TI  - Resistance to Non-glycopeptide Agents in Serious Staphylococcus aureus
      Infections.
AB  - The role of vancomycin in the treatment of serious Staphylococcus aureus
      infections, both methicillin-susceptible and methicillin-resistant, is becoming
      increasingly ineffective due to increasing MIC and failure. The development of
      reduced vancomycin susceptibility by S. aureus to glycopeptides highlights the
      need for clinicians to reexamine the roles of non-glycopeptide therapy. As the
      use of these alternative non-glycopeptides antimicrobials increases, it will
      become pertinent to monitor the rates of resistance. Large surveillance programs
      have provided data for resistance against S. aureus for the non-glycopeptides
      (daptomycin, ceftaroline, tigecycline, linezolid, and tedizolid). The current
      published literatures suggest that worldwide resistance rates to these non
      glycopeptides for serious MRSA infections are still low. Implementation of
      antimicrobial stewardship programs will be crucial in prevention of resistance of
      these antimicrobials against S. aureus.

PMID- 27873127
TI  - Radiotherapy-induced global and regional differences in early-stage left-sided
      versus right-sided breast cancer patients: speckle tracking echocardiography
      study.
AB  - Radiotherapy (RT) to the thoracic region increases late cardiovascular morbidity
      and mortality. The impact of breast cancer laterality on cardiac function is
      largely unknown. The aim of this prospective study was to compare RT-induced
      changes in left-sided and right-sided breast cancer patients using speckle
      tracking echocardiography (STE). Sixty eligible patients with left-sided breast
      cancer and 20 with right-sided breast cancer without chemotherapy were evaluated
      prospectively before and early after RT. A comprehensive echocardiographic
      examination included three dimensional measurements and STE of the left ventricle
      (LV). The global longitudinal strain (GLS) was reduced from -18.3 +/- 3.1 to 
      17.2 +/- 3.3% (p = 0.003) after RT in patients with left-sided breast cancer.
      Similarly, regional analysis showed a reduction in the apical strain from -18.7
      +/- 5.3 to -16.7 +/- 4.9% (p = 0.002) and an increase in basal values from -21.6
      +/- 5.0 to -23.3 +/- 4.9% (p = 0.024). Patients with right-sided breast cancer
      showed deterioration in basal anterior strain segments from -26.3 +/- 7.6 to 
      18.8 +/- 8.9% (p < 0.001) and in pulsed tissue Doppler by 0.825 [0.365, 1.710]
      cm/s (p < 0.001). In multivariable analysis, the use of aromatase inhibitor (beta
      = -2.002, p = 0.001) and decreased LV diastolic volume (beta = -0.070, p = 0.025)
      were independently associated with the decrease in GLS. RT caused no changes in
      conventional LV systolic measurements. RT induced regional changes corresponded
      to the RT fields. Patients with left-sided breast cancer experienced apical
      impact and global decline, whereas patients with right-sided breast cancer showed
      basal changes. The regional differences in cardiac impact warrant different
      methods in screening and in the follow-up of patients with left-sided versus
      right-sided breast cancer.

PMID- 27873128
TI  - Assessment of myocardial delayed enhancement with cardiac computed tomography in
      cardiomyopathies: a prospective comparison with delayed enhancement cardiac
      magnetic resonance imaging.
AB  - To evaluate the feasibility of cardiac CT for the evaluation of myocardial
      delayed enhancement (MDE) in the assessment of patients with cardiomyopathy,
      compared to cardiac MRI. A total of 37 patients (mean age 54.9 +/- 15.7 years, 24
      men) who underwent cardiac MRI to evaluate cardiomyopathy were enrolled. Dual
      energy ECG-gated cardiac CT was acquired 12 min after contrast injection. Two
      observers evaluated cardiac MRI and cardiac CT at different kV settings (100, 120
      and 140 kV) independently for MDE pattern-classification (patchy, transmural,
      subendocardial, epicardial and mesocardial), differentiation between ischemic and
      non-ischemic cardiomyopathy and MDE quantification (percentage MDE). Kappa
      statics and the intraclass correlation coefficient were used for statistical
      analysis. Among different kV settings, 100-kV CT showed excellent agreements
      compared to cardiac MRI for MDE detection (kappa = 0.886 and 0.873,
      respectively), MDE pattern-classification (kappa = 0.888 and 0.881, respectively)
      and differentiation between ischemic and non-ischemic cardiomyopathy (kappa =
      1.000 and 0.893, respectively) for both Observer 1 and Observer 2. The Bland
      Altman plot between MRI and 100-kV CT for the percentage MDE showed a very small
      bias (-0.15%) with 95% limits of agreement of -7.02 and 6.72. Cardiac CT using
      100 kV might be an alternative method to cardiac MRI in the assessment of
      cardiomyopathy, particularly in patients with contraindications to cardiac MRI.

PMID- 27873131
TI  - 2017 National Society of Genetic Counselors Presidential Address: Do Something
      that Scares You.

PMID- 27873129
TI  - Expression of Dixdc1 and its Role in Astrocyte Proliferation after Traumatic
      Brain Injury.
AB  - DIX domain containing 1 (Dixdc1), a positive regulator of Wnt signaling pathway,
      is recently reported to play a role in the neurogenesis. However, the
      distribution and function of Dixdc1 in the central nervous system (CNS) after
      brain injury are still unclear. We used an acute traumatic brain injury (TBI)
      model in adult rats to investigate whether Dixdc1 is involved in CNS injury and
      repair. Western blot analysis and immunohistochemistry showed a time-dependent up
      regulation of Dixdc1 expression in ipsilateral cortex after TBI. Double
      immunofluorescent staining indicated a colocalization of Dixdc1 with astrocytes
      and neurons. Moreover, we detected a colocalization of Ki-67, a cell
      proliferation marker with GFAP and Dixdc1 after TBI. In primary cultured
      astrocytes stimulated with lipopolysaccharide, we found enhanced expression of
      Dixdc1 in parallel with up-regulation of Ki-67 and cyclin A, another cell
      proliferation marker. In addition, knockdown of Dixdc1 expression in primary
      astrocytes with Dixdc1-specific siRNA transfection induced G0/G1 arrest of cell
      cycle and significantly decreased cell proliferation. In conclusion, all these
      data suggest that up-regulation of Dixdc1 protein expression is potentially
      involved in astrocyte proliferation after traumatic brain injury in the rat.

PMID- 27873130
TI  - Phase I clinical and pharmacokinetic study of PM01183 (a tetrahydroisoquinoline,
      Lurbinectedin) in combination with gemcitabine in patients with advanced solid
      tumors.
AB  - Background To determine the recommended dose (RD) of a combination of PM01183 and
      gemcitabine in patients with advanced solid tumors. Methods Forty-five patients
      received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks
      (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dose
      (FD)/gemcitabine 1000 mg/m2 was the highest dose level tested. Dose-limiting
      toxicities (DLTs) were mostly hematological and resulted in the expansion of a
      lower dose level (PM01183 3.5 mg FD/gemcitabine 800 mg/m2); 19 patients at this
      dose level were evaluable but >30% had DLT and >20% had febrile neutropenia. No
      DLT was observed in 11 patients treated at PM01183 3.0 mg FD/gemcitabine 800
      mg/m2, which was defined as the RD. This regimen was feasible and tolerable with
      manageable toxicity; mainly grade 3/4 myelosuppression. Non-hematological
      toxicity comprised fatigue, nausea, vomiting, and transaminases increases.
      Fifteen (33%) patients received >=6 cycles with no cumulative hematological
      toxicity. Pharmacokinetic analysis showed no evidence of drug-drug interaction.
      Nine of 38 patients had response as per RECIST (complete [3%] and partial [21%]),
      for an overall response rate (ORR) of 24% (95% Confidence Interval [CI] 12-40%).
      Eleven patients (29%) had disease stabilization >=4 months. Responses were
      durable (median of 8.5 months): overall median progression-free survival (PFS)
      was 4.2 months (95% CI, 2.7-6.5 months). Conclusions The RD for this combination
      is PM01183 3.0 mg FD (or 1.6 mg/m2)/gemcitabine 800 mg/m2 d1,8 q3wk. This
      schedule is well tolerated and has antitumor activity in several advanced solid
      tumor types.

PMID- 27873132
TI  - Mechanisms of Excessive Extracellular Glutamate Accumulation in Temporal Lobe
      Epilepsy.
AB  - There is compelling evidence that initiation and maintenance of epileptic
      seizures in temporal lobe epilepsy (TLE) is facilitated by excessive accumulation
      in the extracellular (perisynaptic) space of the excitatory neurotransmitter
      glutamate (Glu). This review discusses the mechanisms underlying this phenomenon.
      Glu released from neurons is taken up by astrocytes and activated there by
      glutamine synthetase (GS) to form glutamine (Gln) which upon entry to neurons is
      degraded back to Glu by phosphate-activated glutaminase (PAG): this chain of
      reactions has been defined as the glutamine/glutamate/cycle (GGC). In the initial
      phase of epileptogenesis, increased Glu supply is a consequence of activation of
      its turnover in GGC by Glu released by a primary chemical or physical stimulus.
      In chronic TLE, profound astrogliosis and demise of neurons which culminate in
      hippocampal sclerosis, are associated with changes in GGC which act in concert
      towards increasing the extracellular Glu concentration. Deficiency of GS and of
      the astrocytic Glu transporter, GLT-1, impede Glu inactivation, whereas Glu
      release from neurons appears facilitated by activation of PAG and increased
      activity of the neuronal Glu transporter EAAC1. Conclusions derived from
      measurements of activities/expression patterns of the GGC enzymes and transporter
      moieties find support in metabolic studies employing 13C labeled Glu precursors.
      Glu reuptake by astrocytes is additionally impeded by unfavorable ion gradients
      resulting from ion and water dyshomeostasis, and extracellular Glu concentration
      is further increased by reduction of extracellular space due to edema and altered
      cytoarchitecture of the hippocampus. Missing links in the scenario are discussed
      in concluding comments.

PMID- 27873134
TI  - In reply to Kadri Altundag.

PMID- 27873133
TI  - Altered Expression of CXCL13 and CXCR5 in Intractable Temporal Lobe Epilepsy
      Patients and Pilocarpine-Induced Epileptic Rats.
AB  - The mechanisms that underlie the pathogenesis of epilepsy are still unclear.
      Recent studies have indicated that inflammatory processes occurring in the brain
      are involved in a common and crucial mechanism in epileptogenesis. C-X-C motif
      chemokine ligand 13 (CXCL13) and its only receptor, C-X-C motif chemokine
      receptor 5 (CXCR5), are highly expressed in the central nervous system (CNS) and
      participate in inflammatory responses. The present study aimed to assess the
      expression of CXCL13 and CXCR5 in the brain tissues of both patients with
      intractable epilepsy (IE) and a rat model (lithium-pilocarpine) of temporal lobe
      epilepsy (TLE) to identify possible roles of the CXCL13-CXCR5 signaling pathway
      in epileptogenesis. Real-time quantitative polymerase chain reaction (RT-qPCR),
      immunohistochemical, double-labeled immunofluorescence and Western blot analyses
      were performed in this study. CXCL13 and CXCR5 mRNA expression and protein levels
      were found to be significantly up-regulated in the TLE patients and TLE rats.
      Further, CXCL13 and CXCR5 protein levels were altered during the different
      epileptic phases after onset of status epilepticus (SE) in the pilocarpine model
      rats, including the acute phase (6, 24, and 72 h), latent phase (7 and 14 days)
      and chronic phase (30 and 60 days groups). Moreover, double-labeled
      immunofluorescence analysis revealed that CXCL13 was mainly expressed in the
      cytomembranes and cytoplasm of neurons and astrocytes, while CXCR5 was mainly
      expressed in the cytomembranes and cytoplasm of neurons. Thus, the CXCL13-CXCR5
      signaling pathway may play a possible pathogenic role in IE. CXCL13 and CXCR5 may
      represent potential biomarkers of brain inflammation in epileptic patients.

PMID- 27873136
TI  - Afatinib: A Review in Advanced Non-Small Cell Lung Cancer.
AB  - Afatinib (Giotrif(r), Gilotrif(r)) is an orally administered, irreversible
      inhibitor of the ErbB family of tyrosine kinases. In the first-line treatment of
      patients with advanced lung adenocarcinoma with activating epidermal growth
      factor receptor (EGFR) mutations, afatinib significantly prolonged progression
      free survival (PFS) and time to treatment failure (TTF), but not overall survival
      (OS), compared with gefitinib (LUX-Lung 7 trial). In the overall population of
      patients receiving first-line treatment for advanced lung adenocarcinoma with
      activating EGFR mutations, afatinib significantly prolonged PFS, but not OS,
      compared with pemetrexed plus cisplatin (LUX-Lung 3 trial) or gemcitabine plus
      cisplatin (LUX-Lung 6 trial). However, in both LUX-Lung 3 and LUX-Lung 6, OS was
      significantly prolonged in the subgroup of patients with deletions in exon 19
      receiving afatinib versus chemotherapy. In the second-line treatment of advanced
      squamous non-small cell lung cancer (NSCLC), afatinib significantly prolonged PFS
      and OS, compared with erlotinib, regardless of EGFR mutation status (LUX-Lung 8
      trial). Afatinib had a predictable and manageable tolerability profile in
      patients with advanced NSCLC. In conclusion, afatinib is an important option for
      the first-line treatment of patients with advanced NSCLC and activating EGFR
      mutations, and provides an additional option for the treatment of patients with
      squamous NSCLC that has progressed following first-line platinum-based
      chemotherapy.

PMID- 27873135
TI  - Left atrium: the last bulwark before overt heart failure.
AB  - Heart failure (HF) with preserved ejection fraction (HFpEF) has emerged as an
      important public health issue in recent years. It represents the most common type
      of HF in ambulatory setting, and it has been recognized as a different entity
      from the reduced ejection fraction (EF) form. In HFpEF, continuous growing
      attention has been focused on the role of the left atrium (LA) in preserving good
      ventricular function and asymptomatic condition of the patient since the very
      first stages of diastolic dysfunction (DD). Non-invasive and complete
      echocardiographic evaluation of diastolic phase cannot exempt from accurately
      analyzed LA size, mostly LA volume, and its function, in particular LA myocardial
      deformation by speckle tracking echocardiography (STE). This review examines the
      expanding role of the LA in DD and HFpEF and the importance of its complete
      assessment in various settings, from diagnosis to correlation with major
      cardiovascular events.

PMID- 27873137
TI  - CASPer, an online pre-interview screen for personal/professional characteristics:
      prediction of national licensure scores.
AB  - Typically, only a minority of applicants to health professional training are
      invited to interview. However, pre-interview measures of cognitive skills predict
      for national licensure scores (Gauer et al. in Med Educ Online 21 2016) and
      subsequently licensure scores predict for performance in practice (Tamblyn et al.
      in JAMA 288(23): 3019-3026, 2002; Tamblyn et al. in JAMA 298(9):993-1001, 2007).
      Assessment of personal and professional characteristics, with the same
      psychometric rigour of measures of cognitive abilities, are needed upstream in
      the selection to health profession training programs. To fill that need, Computer
      based Assessment for Sampling Personal characteristics (CASPer)-an on-line, video
      based screening test-was created. In this paper, we examine the correlation
      between CASPer and Canadian national licensure examination outcomes in 109
      doctors who took CASPer at the time of selection to medical school. Specifically,
      CASPer scores were correlated against performance on cognitive and 'non
      cognitive' subsections of both the Medical Council of Canada Qualifying
      Examination (MCCQE) Parts I (end of medical school) and Part II (18 months into
      specialty training). Unlike most national licensure exams, MCCQE has specific
      subcomponents examining personal/professional qualities, providing a unique
      opportunity for comparison. The results demonstrated moderate predictive validity
      of CASPer to national licensure outcomes of personal/professional characteristics
      three to six years after admission to medical school. These types of
      disattenuated correlations (r = 0.3-0.5) are not otherwise predicted by
      traditional screening measures. These data support the ability of a computer
      based strategy to screen applicants in a feasible, reliable test, which has now
      demonstrated predictive validity, lending evidence of its validation for medical
      school applicant selection.

PMID- 27873139
TI  - When Marcel Mauss's Essai sur le Don becomes The Gift: variations on the theme of
      solidarity.
AB  - Since the early 1970s, Marcel Mauss's Essai sur le Don (1923), translated into
      English as The Gift in 1954, has been a standard reference in the social science
      and bioethical literature on the use of human body parts and substances for
      medical and research purposes. At that time, three social scientists-political
      scientist Richard Titmuss in the United Kingdom and sociologist Renee C. Fox
      working with historian Judith Swazey in the United States-had the idea of using
      this concept to highlight the fundamental structure of the biomedical practices
      they were studying, respectively, blood donation, and hemodialysis and organ
      transplantation. The fact that these first applications of Mauss's essay should
      emerge in English- rather than in French-speaking countries raises the question
      of what the translation of the essay, and notably of the word don as gift, may
      have to do with this fact. Reading Mauss in translation undoubtedly inspired a
      seminal approach to interpreting medical and research practices based on bodily
      giving. This article posits that something may have also been lost: a much
      broader concept of giving with unquestionable links to the Durkheimian concept of
      solidarity, which Mauss conceptualizes not only as an obligation but also as a
      liberty to give.

PMID- 27873138
TI  - Photo-enzymatic repair of UVB-induced DNA damage in the two-spotted spider mite
      Tetranychus urticae.
AB  - Ambient ultraviolet-B (UVB) radiation induces lethal effects in the two-spotted
      spider mite Tetranychus urticae, whereas photoreactivation by irradiation with
      ultraviolet-A and visible light (VIS) plays an important role to increase
      survival of mites irradiated by UVB. The physiological mechanisms and ecological
      significance of photoreactivation in terrestrial arthropods have not been shown
      clearly. We verified the biological impact and accumulation of DNA lesions by UVB
      irradiation and the repair of them by photoreactivation in T. urticae larvae.
      Survival of UVB-irradiated larvae decreased with increasing UVB dose, but
      recovered remarkably with VIS exposure after UVB irradiation (photoreactivation).
      The DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine
      pyrimidine photoproducts (6-4PPs) linearly increased with the UVB dose. The CPDs
      were repaired after exposure to VIS, whereas the frequency of 6-4PPs was
      unaffected by VIS; CPD photolyase genes, but not (6-4) photolyase genes, have
      been found in the T. urticae genome. Therefore, DNA damage and CPD photo
      enzymatic repair (PER) is significant for survival in this mite under ambient UVB
      radiation. Unexpectedly, gene expression of CPD photolyase was unaffected by
      irradiation with UVB and VIS. Instead, expression of xeroderma pigmentosum A
      (XPA) was increased by irradiation. XPA is a core factor in nucleotide excision
      repair (NER), which is a repair system unrelated to photo energy. The
      relationship between gene expression and enzymatic repair remains unclear. To
      elucidate the PER process in T. urticae, further study will be necessary on the
      gene expression patterns and molecular functions of CPD photolyase in PER and of
      XPA in NER.

PMID- 27873140
TI  - Cross-Cultural Validity of the Social Communication Questionnaire for Adults with
      Intellectual Developmental Disorder.
AB  - Diagnosing Autism Spectrum Disorders (ASD) is important throughout the lifespan.
      The objective was to investigate the transcultural diagnostic validity of the
      Social Communication Questionnaire (SCQ) in a clinical sample of 451 adults with
      Intellectual Developmental Disorder (IDD) with and without ASD in Germany, the
      U.S.A. and Great Britain. Variables associated with higher SCQ sum-scores were
      higher levels of IDD, male gender, a diagnosis of ASD and the study site (Germany
      > U.S.A > G.B.). An ROC analysis revealed a cut-score of 13, which resulted in a
      sensitivity of 0.87 and a specificity of 0.58. It is recommended to adjust the
      cut-score according to level of IDD and gender. Further research is needed to
      align diagnostic assignment of ASD across different sites and countries.

PMID- 27873142
TI  - University Hospital Waterford: 5-year experience of cutaneous melanoma.
AB  - INTRODUCTION: The incidence of cutaneous melanoma (CM) continues to rise in
      Ireland. Despite significant advances in melanoma molecular therapy, surgery
      remains the mainstay of treatment for CM. The University Hospital Waterford (UHW)
      prospectively maintained CM registry was established in 2010. AIM: To summarize 5
      year experience (2010-2015) of primary CM presenting to UHW. METHODS: Data were
      retrospectively obtained from a central electronic pathology and radiology
      repository augmented by HIPE data and theatre logs. Data collected included
      patient demographics and clinico-pathological characteristics, specimen number,
      size, anatomical location, melanoma subtype, Breslow thickness, Clark's level,
      ulceration, and mitosis. RESULTS: 592 CMs were managed in UHW during the study
      period. Overall, females comprised the majority of cases with mean age at
      presentation 60.78 +/- 18.29 years. The most commonly affected anatomical
      location was the lower limb (26.7%) followed by the back (15.1%), upper limb
      (15.07%), and face (14.40%). Superficial spreading and lentigo maligna were the
      most common histological subtype accounting for 19.8 and 20%, respectively.
      Overall, the mean Breslow depth was 2.4 +/- 3.7 mm with corresponding Clark's
      Level III. Sentinel lymph node positivity was 39/103 (37.89%) most commonly
      located in the axilla (53.8%) and groin (30.7%). CONCLUSION: There has been a
      steady increase in the number of cutaneous melanoma presentations over the past 5
      years to the South East Cancer Centre. Patients are managed best by prompt
      surgical excision and multidisciplinary management. Our results are in keeping
      with international standards and work continues in determining overall 5-year
      survival and recurrence rates.

PMID- 27873141
TI  - The Contribution of Maternal ADHD Symptomatology, Maternal DAT1, and Home
      Atmosphere to Child ADHD Symptomatology at 7 Years of Age.
AB  - Children of mothers with attention-deficit/hyperactivity disorder (ADHD) have an
      increased genetic and environmental risk for ADHD. The unique and interactive
      contributions of a maternal dopamine receptor gene (DAT1), maternal ADHD symptoms
      (hyperactive- impulsive, inattentive), and home atmosphere to the prediction of
      ADHD symptoms (hyperactive- impulsive, inattentive) in 7- year-old boys (N = 96)
      were examined using data from a longitudinal study of familial risk for ADHD.
      During the first 6 months of the study, mothers and their spouses completed a
      questionnaire about the mother's ADHD symptoms. Home atmosphere questionnaire
      data were collected 4 years later. At the 7-year assessment, mothers reported on
      their child's ADHD symptoms. Negative home atmosphere was significantly
      associated with child hyperactive-impulsive and inattentive symptoms. Maternal
      inattentive symptoms were significantly correlated with both child symptom
      dimensions. Regression models, with child genotype and maternal education
      controlled, showed main effects for maternal inattentive symptoms, maternal DAT1
      10/10 genotype, and home atmosphere in the prediction of child inattentive
      symptoms. Only home atmosphere predicted child hyperactive-impulsive symptoms.
      There was a significant home atmosphere x maternal hyperactive-impulsive symptoms
      interaction in the prediction of child hyperactive-impulsive symptoms. Boys with
      higher levels of symptoms came from homes characterized by higher levels of
      negative atmosphere and had mothers with higher levels of hyperactive-impulsive
      symptoms. There was also a trend (p = 0.075) for a maternal DAT1 x home
      atmosphere interaction. Boys with higher levels of inattentive symptoms came from
      homes with higher levels of negative atmosphere and had mothers with the
      homozygous 10/10 genotype. The maternal heterozygous 9/10 genotype did not
      predict child symptoms.

PMID- 27873143
TI  - Regulation of Rac1 GTPase activity by quinine through G-protein and bitter taste
      receptor T2R4.
AB  - Rac1 belongs to the Rho family of small GTPases and regulates actin cytoskeleton
      reorganization. T2R4 is a bitter taste receptor belonging to the G protein
      coupled receptor family of proteins. In addition to mediating bitter taste
      perception from the tongue, T2R4s are found in extra-oral tissues, e.g., nasal
      epithelium, airways, brain, testis suggesting a much broader physiological
      function for these receptors. Anti-malarial drug and a bitter tasting compound,
      quinine, is a known agonist for T2R4, whereas BCML (Nalpha,Nalpha
      Bis(carboxymethyl)-L-lysine) acts as an inverse agonist. Using western blot and
      Ca++ mobilization assays, the effects of quinine on Rac1 activity in HEK293T
      cells stably expressing T2R4/Galpha16/44, T2R4, or Galpha16/44 and transiently
      transfected with HA-Rac1 were investigated. Quinine treatment caused a
      significant reduction in the amount of active Rac1, whereas in the presence of
      BCML, quinine failed to cause any significant change in active Rac1. No
      significant change in Rac1 activity was observed in BAPTA-AM plus quinine-treated
      Galpha16/44 cells, suggesting possibility of a pathway in addition to the
      canonical Ca++-dependent pathway. A noticeable role for Galpha16/44 independent
      of T2R4 is observed in quinine-mediated Rac1 inactivation. Further, a significant
      difference in quinine-induced Ca++ response in T2R4/Galpha16/44 or T2R4 cells was
      observed validating the partial role of calcium and importance of Galpha16/44.
      This study is the first to show an inhibitory downstream action of a T2R4 agonist
      on Rac1 function. Further investigation will help in better understanding the
      downstream signal transduction network of T2R4 and its extra-oral physiological
      roles.

PMID- 27873144
TI  - Truncation of the MSH2 C-terminal 60 amino acids disrupts effective DNA mismatch
      repair and is causative for Lynch syndrome.
AB  - Missense variants of DNA mismatch repair (MMR) genes pose a problem in clinical
      genetics as long as they cannot unambiguously be assigned as the cause of Lynch
      syndrome (LS). To study such variants of uncertain clinical significance, we have
      developed a functional assay based on direct measurement of MMR activity in mouse
      embryonic stem cells expressing mutant protein from the endogenous alleles. We
      have applied this protocol to a specific truncation mutant of MSH2 that removes
      60 C-terminal amino acids and has been found in suspected LS families. We show
      that the stability of the MSH2/MSH6 heterodimer is severely perturbed, causing
      attenuated MMR in in vitro assays and cancer predisposition in mice. This
      mutation can therefore unambiguously be considered as deleterious and causative
      for LS.

PMID- 27873145
TI  - Use of refrigerant spray of a propane/butane/isobutane gas mixture in the
      management of keratocystic odontogenic tumors: a preliminary study.
AB  - PURPOSE: Keratocystic odontogenic tumor (KCOT) is an aggressive benign tumor and
      the management by complete enucleation followed by cryotherapy maintains the
      inorganic bone matrix, resulting in better repair and reduces the rates of
      recurrence. A refrigerant spray with a propane/butane/isobutane gas mixture has
      been pointed to as an alternative to liquid nitrogen, because the device is easy
      to handle and contain within the cavity, providing better control and lower risk
      of injury to the adjacent soft tissue. Thus, the aim of this study was to
      evaluate the outcome of enucleation followed by cryosurgery using a refrigerant
      spray of this gas mixture in ten patients diagnosed with KCOT. METHOD: The
      biggest lesions received a prior treatment consisting of marsupialization to
      decrease the tumor size. During the surgeries, the lesions were removed by
      enucleation and the surgical site was sprayed with the gas mixture. RESULTS:
      Wound dehiscence was observed in all cases, which healed by the second intention.
      The mean follow-up period was 64.3 months (range 24-120 months). Eight of the ten
      patients showed no evidence of clinical or radiographic recurrence. Pathologic
      fractures and infections were not observed. CONCLUSIONS: The results obtained
      suggest that enucleation followed by cryosurgery is an effective therapy for
      managing KCOT.

PMID- 27873147
TI  - Fully automated MR liver volumetry using watershed segmentation coupled with
      active contouring.
AB  - PURPOSE: Our purpose is to develop a fully automated scheme for liver volume
      measurement in abdominal MR images, without requiring any user input or
      interaction. METHODS: The proposed scheme is fully automatic for liver volumetry
      from 3D abdominal MR images, and it consists of three main stages: preprocessing,
      rough liver shape generation, and liver extraction. The preprocessing stage
      reduced noise and enhanced the liver boundaries in 3D abdominal MR images. The
      rough liver shape was revealed fully automatically by using the watershed
      segmentation, thresholding transform, morphological operations, and statistical
      properties of the liver. An active contour model was applied to refine the rough
      liver shape to precisely obtain the liver boundaries. The liver volumes
      calculated by the proposed scheme were compared to the "gold standard" references
      which were estimated by an expert abdominal radiologist. RESULTS: The liver
      volumes computed by using our developed scheme excellently agreed (Intra-class
      correlation coefficient was 0.94) with the "gold standard" manual volumes by the
      radiologist in the evaluation with 27 cases from multiple medical centers. The
      running time was 8.4 min per case on average. CONCLUSIONS: We developed a fully
      automated liver volumetry scheme in MR, which does not require any interaction by
      users. It was evaluated with cases from multiple medical centers. The liver
      volumetry performance of our developed system was comparable to that of the gold
      standard manual volumetry, and it saved radiologists' time for manual liver
      volumetry of 24.7 min per case.

PMID- 27873146
TI  - Comparison of Dialysis- and Solvatofluorochromism-Based Methods to Determine Drug
      Release Rates from Polymer Nanoassemblies.
AB  - PURPOSE: To compare traditional dialysis- and novel solvatofluorochromism (SFC)
      based methods for accurate determination of drug release profiles for
      nanoparticle drug carriers. METHODS: Polymer nanoassemblies (PNAs) varying in
      drug release patterns were prepared using poly(ethylene glycol),
      poly(ethylenimine), hydrophobic excipients (palmitate and deoxycholate), and
      model hydrophobic anticancer drugs with clinical relevance (carfilzomib and
      docetaxel). Nile blue (NB) was used as a model SFC dye quenching fluorescence in
      water yet emitting strong fluorescence in the presence of hydrophobic drugs
      within PNAs. Drug release kinetics were measured by dialysis- and SFC-based
      methods, and analyzed by mathematical modeling of free drug, spiked drug, and
      encapsulated drug release. RESULTS: The dialysis method overestimated drug
      remaining in PNAs because it included released drug in measurements, whereas the
      SFC method successfully distinguished drugs entrapped in PNAs from released in
      solution and thus provided more accurate drug release patterns. However,
      mathematical modeling revealed that the dialysis method would be less influenced
      than the SFC method by hydrophobic excipients modulating drug diffusion within
      PNAs. CONCLUSIONS: In comparison to the dialysis-based method, the SFC-based
      method would allow for real-time spectroscopic determination of drug release from
      PNAs and potentially other nanoparticle drug carriers with improved convenience
      and accuracy.

PMID- 27873149
TI  - Erratum to: Quantifying Adventitious Error in a Covariance Structure as a Random
      Effect.

PMID- 27873150
TI  - Commemorating the 80th Anniversary of the Founding of Psychometrika: Introduction
      by the Guest Editors.

PMID- 27873148
TI  - Local texture descriptors for the assessment of differences in diffusion magnetic
      resonance imaging of the brain.
AB  - PURPOSE: Descriptors extracted from magnetic resonance imaging (MRI) of the brain
      can be employed to locate and characterize a wide range of pathologies. Scalar
      measures are typically derived within a single-voxel unit, but neighborhood-based
      texture measures can also be applied. In this work, we propose a new set of
      descriptors to compute local texture characteristics from scalar measures of
      diffusion tensor imaging (DTI), such as mean and radial diffusivity, and
      fractional anisotropy. METHODS: We employ weighted rotational invariant local
      operators, namely standard deviation, inter-quartile range, coefficient of
      variation, quartile coefficient of variation and skewness. Sensitivity and
      specificity of those texture descriptors were analyzed with tract-based spatial
      statistics of the white matter on a diffusion MRI group study of elderly healthy
      controls, patients with mild cognitive impairment (MCI), and mild or moderate
      Alzheimer's disease (AD). In addition, robustness against noise has been assessed
      with a realistic diffusion-weighted imaging phantom and the contamination of the
      local neighborhood with gray matter has been measured. RESULTS: The new texture
      operators showed an increased ability for finding formerly undetected differences
      between groups compared to conventional DTI methods. In particular, the
      coefficient of variation, quartile coefficient of variation, standard deviation
      and inter-quartile range of the mean and radial diffusivity detected significant
      differences even between previously not significantly discernible groups, such as
      MCI versus moderate AD and mild versus moderate AD. The analysis provided
      evidence of low contamination of the local neighborhood with gray matter and high
      robustness against noise. CONCLUSIONS: The local operators applied here enhance
      the identification and localization of areas of the brain where cognitive
      impairment takes place and thus indicate them as promising extensions in
      diffusion MRI group studies.

PMID- 27873151
TI  - A Stereotactic Probabilistic Atlas for the Major Cerebral Arteries.
AB  - Improved whole brain angiographic and velocity-sensitive MRI is pushing the
      boundaries of noninvasively obtained cerebral vascular flow information. The
      complexity of the information contained in such datasets calls for automated
      algorithms and pipelines, thus reducing the need of manual analyses by trained
      radiologists. The objective of this work was to lay the foundation for such
      automated pipelining by constructing and evaluating a probabilistic atlas
      describing the shape and location of the major cerebral arteries. Specifically,
      we investigated how the implementation of a non-linear normalization into
      Montreal Neurological Institute (MNI) space improved the alignment of individual
      arterial branches. In a population-based cohort of 167 subjects, age 64-68 years,
      we performed 4D flow MRI with whole brain volumetric coverage, yielding both
      angiographic and anatomical data. For each subject, sixteen cerebral arteries
      were manually labeled to construct the atlas. Angiographic data were normalized
      to MNI space using both rigid-body and non-linear transformations obtained from
      anatomical images. The alignment of arterial branches was significantly improved
      by the non-linear normalization (p < 0.001). Validation of the atlas was based on
      its applicability in automatic arterial labeling. A leave-one-out validation
      scheme revealed a labeling accuracy of 96 %. Arterial labeling was also performed
      in a separate clinical sample (n = 10) with an accuracy of 92.5 %. In conclusion,
      using non-linear spatial normalization we constructed an artery-specific
      probabilistic atlas, useful for cerebral arterial labeling.

PMID- 27873152
TI  - A Comparison of Pharmacokinetic and Pharmacodynamic Properties Between Faster
      Acting Insulin Aspart and Insulin Aspart in Elderly Subjects with Type 1 Diabetes
      Mellitus.
AB  - BACKGROUND: Due to population aging, an increasing number of elderly patients
      with diabetes use insulin. It is therefore important to investigate the
      characteristics of new insulins in this population. Faster-acting insulin aspart
      (faster aspart) is insulin aspart (IAsp) in a new formulation with faster
      absorption. This study investigated the pharmacological properties of faster
      aspart in elderly subjects with type 1 diabetes mellitus (T1DM). METHODS: In a
      randomised, double-blind, two-period crossover trial, 30 elderly (>=65 years) and
      37 younger adults (18-35 years) with T1DM received single subcutaneous faster
      aspart or IAsp dosing (0.2 U/kg) and underwent an euglycaemic clamp (target 5.5
      mmol/L) for up to 12 h. RESULTS: The pharmacokinetic and pharmacodynamic time
      profiles were left-shifted for faster aspart versus IAsp. In each age group,
      onset of appearance occurred approximately twice as fast (~3 min earlier) and
      early exposure (area under the concentration-time curve [AUC] for serum IAsp from
      time zero to 30 min [AUCIAsp,0-30 min]) was greater (by 86% in elderly and 67% in
      younger adults) for faster aspart than for IAsp. Likewise, onset of action
      occurred 10 min faster in the elderly and 9 min faster in younger adults, and
      early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time
      zero to 30 min [AUCGIR,0-30 min]) was greater (by 109%) for faster aspart than
      for IAsp in both age groups. Total exposure (AUCIAsp,0-t) and the maximum
      concentration (C max) for faster aspart were greater (by 30 and 28%,
      respectively) in elderly than in younger adults. No age group differences were
      seen for the total (AUCGIR,0-t) or maximum (GIRmax) glucose-lowering effect.
      CONCLUSION: This study demonstrated that the ultra-fast pharmacological
      properties of faster aspart are similar in elderly subjects and younger adults
      with T1DM. ClinicalTrials.gov Identifier: NCT02003677.

PMID- 27873153
TI  - Preoperative determinant of early postoperative renal function following radical
      cystectomy and intestinal urinary diversion.
AB  - PURPOSE: To identify preoperative factors correlated with postoperative early
      renal function in patients who had undergone radical cystectomy (RC) and
      intestinal urinary diversion. METHODS: We retrospectively identified 201
      consecutive bladder cancer patients without distant metastasis who had undergone
      RC at our institution between 2003 and 2012. The estimated glomerular filtration
      rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology
      equation before RC and 3 months following RC. Univariate and stepwise multiple
      linear regression analyses were applied to estimate postoperative renal function
      and to identify significant preoperative predictors of postoperative renal
      function. RESULTS: Patients who had undergone intestinal urinary diversion and
      were available for the collection of follow-up data (n = 164) were eligible for
      the present study. Median preoperative and postoperative eGFRs were 69.7
      (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In
      univariate analyses, age, preoperative proteinuria, thickness of abdominal
      subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative
      eGFR, and urinary diversion type were significantly associated with postoperative
      eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age,
      and TSF were significant factors for predicting postoperative eGFR (p < 0.001, p
      = 0.02, and p = 0.046, respectively). The estimated postoperative eGFRs
      correlated well with the actual postoperative eGFRs (r = 0.65, p < 0.001).
      CONCLUSIONS: Preoperative eGFR, age, and TSF were independent preoperative
      factors for determining postoperative renal function in patients who had
      undergone RC and intestinal urinary diversion. These results may be used for
      patient counseling before surgery, including the planning of perioperative
      chemotherapy administration.

PMID- 27873154
TI  - Editorial: Autism - Hype and Hope.

PMID- 27873156
TI  - Erratum to: Predictive role of dynamic contrast enhanced T1-weighted MR sequences
      in pre-surgical evaluation of macroadenomas consistency.

PMID- 27873155
TI  - Physiology-based regularization of the electrocardiographic inverse problem.
AB  - The inverse problem of electrocardiography aims at noninvasively reconstructing
      electrical activity of the heart from recorded body-surface electrocardiograms. A
      crucial step is regularization, which deals with ill-posedness of the problem by
      imposing constraints on the possible solutions. We developed a regularization
      method that includes electrophysiological input. Body-surface potentials are
      recorded and a computed tomography scan is performed to obtain the torso-heart
      geometry. Propagating waveforms originating from several positions at the heart
      are simulated and used to generate a set of basis vectors representing spatial
      distributions of potentials on the heart surface. The real heart-surface
      potentials are then reconstructed from the recorded body-surface potentials by
      finding a sparse representation in terms of this basis. This method, which we
      named 'physiology-based regularization' (PBR), was compared to traditional
      Tikhonov regularization and validated using in vivo recordings in dogs. PBR
      recovered details of heart-surface electrograms that were lost with traditional
      regularization, attained higher correlation coefficients and led to improved
      estimation of recovery times. The best results were obtained by including
      approximate knowledge about the beat origin in the PBR basis.

PMID- 27873157
TI  - Eicosapentaenoic acid triggers Ca2+ release and Ca2+ influx in mouse cerebral
      cortex endothelial bEND.3 cells.
AB  - Eicosapentaenoic acid (EPA), an omega-3 fatty acid abundant in fish oil, protects
      endothelial cells (EC) from lipotoxicity and triggers EC NO release. The latter
      is related to an elevation of cytosolic Ca2+. Although EPA has been shown to
      cause human EC cytosolic Ca2+ elevation, the mechanism is unclear.
      Microfluorimetric imaging was used here to measure free cytosolic Ca2+
      concentration. EPA was shown to cause intracellular Ca2+ release in mouse
      cerebral cortex endothelial bEND.3 cells; interestingly, the EPA-sensitive
      intracellular Ca2+ pool(s) appeared to encompass and was larger than the Ca2+
      pool mobilized by sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition by
      cyclopiazonic acid. EPA also opened a Ca2+ influx pathway pharmacologically
      distinct from store-operated Ca2+ influx. Surprisingly, EPA-triggered Ca2+ influx
      was Ni2+-insensitive; and EPA did not trigger Mn2+ influx. Further, EPA-triggered
      Ca2+ influx did not involve Na+-Ca2+ exchangers. Thus, our results suggest EPA
      triggered unusual mechanisms of Ca2+ release and Ca2+ influx in EC.

PMID- 27873158
TI  - Feasibility and Importance of Enteroscopy after Gastric Bypass.
AB  - BACKGROUND: Bariatric surgery has increased in popularity, with Roux-en-Y Gastric
      Bypass (RYGB) being one of the most frequently performed. This leads to many
      cases in which the stomach is removed from routine gastroscopy access, sometimes
      being a major source of concern. Performing enteroscopy in these patients is
      technically difficult. We present our experience with 24 cases in which the aim
      was to access the detached stomach. METHODS: Retrospective analysis on RYGB
      enteroscopy procedures aimed to access the detached stomach. Data recorded:
      demographic parameters, indication, gas insufflation, time to bypass stomach,
      total procedure and recovery times, and endoscopic and pathological findings.
      RESULTS: This study included 24 patients who underwent RYGB in the previous 3-36
      months. Indications were chronic abdominal pain, refractory anemia, or
      unexplainable weight loss. Detached stomach was accessed in 79% of patients.
      Access time ranged from 25 to 55 min. Recovery time for all procedures was 86.66
      min on average and shorter with CO2 insufflation (42.5 min). All detached
      stomachs showed macroscopic gastritis; four of them were Helicobacter pylori
      positive. Significant findings included three patients with jejunojejunostomy
      stenosis and one patient with a marginal gastrojejunal ulcer, which was later
      diagnosed with Signet ring cell carcinoma of the proximal anastomosis.
      CONCLUSIONS: We present the feasibility and importance of enteroscopy of the
      detached stomach and believe that this procedure should be performed more
      frequently. A high index of suspicion is needed for postoperative symptoms in
      order to exclude significant pathologies and reassure symptomatic patients that
      there is no abnormality in the bypassed stomach.

PMID- 27873161
TI  - FGF treatment of host embryos injected with ES cells increases rates of
      chimaerism.
AB  - In spite of the emergence of genome editing tools, ES cell mediated transgenesis
      remains the most controllable way of creating genetically modified animals.
      Although tetraploid (4N) complementation of 4N host embryos and ES cells, is the
      only method guaranteeing that offspring are entirely ES cell derived, this
      technique is challenging, not always successful and difficult to implement in
      some laboratory settings. The current study shows that pretreatment of host
      blastocysts with FGF4 prior to ES cell injection can provide an alternative
      method for the generation of animals displaying high rates of chimaerism.
      Chimaerism assessment in E11 fetuses and born pups shows that a large percentage
      of resulting conceptuses show a high ES cell contribution from implantation
      onwards and that developing pups do not necessitate c-section for delivery.

PMID- 27873159
TI  - Are too many inferior vena cava filters used? Controversial evidences in
      different clinical settings: a narrative review.
AB  - The use of inferior vena cava filters to prevent pulmonary embolism is increasing
      mainly because of indications that appear to be unclearly codified and
      recommended. The evidence supporting this approach is often heterogeneous, and
      mainly based on observational studies and consensus opinions, while the insertion
      of an IVC filter exposes patients to the risk of complications and increases
      health care costs. Thus, several proposed indications for an IVC filter placement
      remain controversial. We attempt to review the proof on the efficacy and safety
      of IVC filters in several "special" clinical settings, and assess the robustness
      of the available evidence for any specific indication to place an IVC filter.

PMID- 27873160
TI  - Prognostic Significance of CD44 and Orthopedia Homeobox Protein (OTP) Expression
      in Pulmonary Carcinoid Tumours.
AB  - CD44 and orthopedia homeobox protein (OTP) expressions have shown to be
      predictive of overall survival in pulmonary carcinoid (PC) tumours. The scope of
      the present study was to validate their role in PC patients and investigate
      potential application in clinical practice. Data was collected from patients
      presenting to a tertiary cancer centre diagnosed with PC between 2003 and 2015.
      Diagnosis was confirmed by central pathology review. Formalin-fixed paraffin
      embedded (FFPE) tissue samples collected at diagnosis were scored using
      immunohistochemistry (H score) for standard CD44 and nuclear and cytoplasmic OTP
      protein expression. The study included 108 patients. High CD44/nuclear OTP (nOTP)
      expression was strongly associated with typical carcinoid (TC) histology (p <
      0.001). Eighty-six patients, who underwent radical surgical resection, were
      selected to assess the impact of patient and tumour parameters on relapse-free
      survival (RFS). Sixty-nine (80 %) had TC and 17 (20 %) had atypical carcinoid
      tumours. On multivariate analysis, high CD44 and nOTP expression, TC histology
      and non-infiltrative tumour growth were associated with superior RFS. Early stage
      TC (stage pT1aN0) patients (N = 32; 46 %) had excellent prognosis irrespective of
      CD44/nOTP status. Importantly, TC patients with locally advanced disease (defined
      as >pT1aN0) and high CD44/nOTP expression (N = 26; 38 %) had excellent RFS (p =
      0.005) compared to those with the same stage but low CD44 and/or nOTP (N = 11; 16
      %). Additionally, the combination of CD44/nOTP expression and tumour growth
      pattern led to a more accurate prognostic system compared to the established WHO
      classification of PC tumours (concordance index = 0.902 vs 0.811, respectively, p
      < 0.001). Assessment of CD44/nOTP expression combined with tumour growth pattern
      identifies clear groups with largely different prognosis. These findings provide
      important information on how patients with these resected cancers should be
      followed up.

PMID- 27873162
TI  - Metabolism of sn-1(3)-Monoacylglycerol and sn-2-Monoacylglycerol in Caecal
      Enterocytes and Hepatocytes of Brown Trout (Salmo trutta).
AB  - sn-2-Monoacylglycerol (2-MAG) and sn-1(3)-monoacylglycerol [1(3)-MAG] are
      important but yet little studied intermediates in lipid metabolism. The current
      study compared the metabolic fate of 2-MAG and 1(3)-MAG in isolated caecal
      enterocytes and hepatocytes of brown trout (Salmo trutta). 1(3)-Oleoyl [9,10
      3H(N)]-glycerol and 2-Oleoyl [9,10-3H(N)]-glycerol were prepared by pancreatic
      lipase digestion of triolein [9,10-3H(N)]. The 1(3)-MAG and 2-MAG were
      efficiently absorbed by enterocytes and hepatocytes at similar rates. The 2-MAG
      was quickly resynthesized into TAG through the monoacylglycerol acyltransferase
      (EC: 2.3.1.22, MGAT) pathway in both tissues, whereas 1(3)-MAG was processed into
      TAG and phospholipids at a much slower rate, suggesting 2-MAG was the preferred
      substrates for MGAT. Further analysis showed that 1(3)-MAG was synthesized into
      1,3-DAG, but there were no accumulation of 1,3-DAG in either enterocytes or
      hepatocytes, which contrasts that of mammalian studies. Some of the 1(3)-MAG may
      be acylated to 1,2(2,3)-DAG and then utilized for TAG synthesis. Alternatively,
      1(3)-MAG can be hydrolyzed to free fatty acid and glycerol, and re-synthesized
      into TAG through the glycerol-3-phosphate (Gro-3-P) pathway. The overall data
      suggested that the limiting step of the intracellular 1(3)-MAG metabolism is the
      conversion of 1(3)-MAG itself.

PMID- 27873164
TI  - Bacterial signals N-acyl homoserine lactones induce the changes of morphology and
      ethanol tolerance in Saccharomyces cerevisiae.
AB  - The bacterial quorum sensing signals N-acyl homoserine lactone (AHL) signals are
      able to regulate a diverse array of physiological activities, such as symbiosis,
      virulence and biofilm formation, depending on population density. Recently, it
      has been discovered that the bacterial quorum sensing (QS) signal molecules can
      induce extensive response of higher eukaryotes including plants and mammalian
      cells. However, little is known about the response of fungi reacting to these
      bacterial signals. Here we showed that Saccharomyces cerevisiae, as an ancient
      eukaryote and widely used for alcoholic beverage and bioethanol production,
      exposed to short-chain 3-OC6-HSL and long-chain C12-HSL appeared obvious changes
      in morphology and ethanol tolerance. AHLs could increase the frequency of cells
      with bipolar and multipolar buds, and these changes did not present distinct
      differences when induced by different types (3-OC6-HSL and C12-HSL) and varied
      concentrations (200 nM and 2 MUM) of AHLs. Further investigation by flow
      cytometer displayed that the cells untreated by AHLs reduced cell size (decreased
      FSC) and enhanced intracellular density (increased in SSC), compared with the
      AHLs-induced cells after incubation 6 h. In addition, the long-chain C12-HSL
      could slightly increase the ethanol tolerance of S. cerevisiae while the short
      chain HSL obviously decreased it. Our study would be valuable to further research
      on the interaction between prokaryotic and eukaryotic microbes, and be reference
      for industrial production of bioethanol.

PMID- 27873166
TI  - A dangerous hobby? Erysipelothrix rhusiopathiae bacteremia most probably acquired
      from freshwater aquarium fish handling.
AB  - Erysipelothrix rhusiopathiae is a facultative anaerobic Gram-positive rod that
      occurs widely in nature and is best known in veterinary medicine for causing
      swine erysipelas. In humans, infections are rare and mainly considered as
      occupationally acquired zoonosis. A case of E. rhusiopathiae bacteremia most
      likely associated with home freshwater aquarium handling is reported. The route
      of transmission was probably a cut with the dorsal fin of a dead pet fish. A
      short review of clinical presentations, therapeutic considerations and pitfalls
      of E. rhusiopathiae infections in humans is presented.

PMID- 27873165
TI  - Analysing the effect of I1 imidazoline receptor ligands on DSS-induced acute
      colitis in mice.
AB  - Imidazoline receptors (IRs) have been recognized as promising targets in the
      treatment of numerous diseases; and moxonidine and rilmenidine, agonists of I1
      IRs, are widely used as antihypertensive agents. Some evidence suggests that IR
      ligands may induce anti-inflammatory effects acting on I1-IRs or other molecular
      targets, which could be beneficial in patients with inflammatory bowel disease
      (IBD). On the other hand, several IR ligands may stimulate also alpha2
      adrenoceptors, which were earlier shown to inhibit, but in more recent studies to
      rather aggravate colitis. Hence, this study aimed to analyse for the first time
      the effect of various I1-IR ligands on intestinal inflammation. Colitis was
      induced in C57BL/6 mice by adding dextran sulphate sodium (DSS) to the drinking
      water for 7 days. Mice were treated daily with different IR ligands: moxonidine
      and rilmenidine (I1-IR agonists), AGN 192403 (highly selective I1-IR ligand,
      putative antagonist), efaroxan (I1-IR antagonist), as well as with the endogenous
      IR agonists agmatine and harmane. It was found that moxonidine and rilmenidine at
      clinically relevant doses, similarly to the other IR ligands, do not have a
      significant impact on the macroscopic and histological signs of DSS-evoked
      inflammation. Likewise, colonic myeloperoxidase and serum interleukin-6 levels
      remained unchanged in response to these agents. Thus, our study demonstrates that
      imidazoline ligands do not influence significantly the severity of DSS-colitis in
      mice and suggest that they probably neither affect the course of IBD in humans.
      However, the translational value of these findings needs to be verified with
      other experimental colitis models and human studies.

PMID- 27873167
TI  - Myocardial perfusion and left ventricular quantitative parameters obtained using
      gated myocardial SPECT: Comparison of three software packages.
AB  - BACKGROUND: The aim of the present study was to compare Emory Cardiac Toolbox,
      Myovation, and Quantitative Gated SPECT software regarding the automatic
      measurements of perfusion and functional left ventricular (LV) quantitative
      parameters, summed stress score (SSS), perfusion defect score, LV ejection
      fraction (LVEF), end-diastolic volume, and end-systolic volume (ESV). METHODS AND
      RESULTS: 99mTc-tetrofosmin gated SPECT studies were performed in 634 consecutive
      patients based on the one-day stress/rest protocol. Participants were divided
      into subgroups according to heart size (ESV cut-off value: 25 mL), perfusion (SSS
      >/<=3), and other patient/protocol-related factors. LVEF was categorized as
      normal (>=50%), mildly moderately impaired (35-49%), and severely abnormal
      (<35%). The concordance between the packages was good to excellent, in overall
      population, ESV <=25 mL, ESV >25 mL, and SSS >3 subgroups (intraclass correlation
      coefficients, ICCs 0.73-0.93). In SSS <=3 subgroup, the correlation was excellent
      for LV functional parameters, but suboptimal for perfusion variables (ICCs 0.30
      0.83). LVEF categorization revealed similar variability (discordance 18.1 and
      11.1% for stress/rest LVEF values, respectively). Pair comparisons demonstrated
      considerable differences concerning all parameters for all patient subgroups. The
      statistical significance of our findings by ESV and SSS classifications was
      evaluated. CONCLUSIONS: Despite the significant concordance between software
      packages, considerable differences in mean values of myocardial perfusion and LV
      functional parameters were demonstrated.

PMID- 27873163
TI  - An Update on the Use of Immunomodulators in Primary Immunodeficiencies.
AB  - The genomic revolution in the past decade fuelled by breathtaking advances in
      sequencing technologies has defined several new genetic diseases of the immune
      system. Many of these newly characterized diseases are a result of defects in
      genes involved in immune regulation. The discovery of these diseases has opened a
      vista of new therapeutic possibilities. Immunomodulatory agents, a hitherto
      unexplored therapeutic option in primary immunodeficiency diseases have been
      tried in a host of these newly described maladies. These agents have been shown
      conclusively to favorably modulate immune responses, resulting in abatement of
      clinical manifestations both in experimental models and patients. While some of
      the treatment options have been approved for therapeutic use or have been shown
      to be of merit in open-label trials, others have been shown to be efficacious in
      a handful of clinical cases, animal models, and cell lines. Interferon gamma is
      approved for use in chronic granulomatous disease (CGD) to reduce the burden of
      infection and and has a good long-term efficacy. Recombinant human IL7 therapy
      has been shown increase the peripheral CD4 and CD8 T cell counts in patients with
      idiopathic CD4. Anti-IL1 agents are approved for the management of cryopyrin
      related autoinflammatory syndrome, and their therapeutic efficacy is being
      increasingly recognized in other autoinflammatory syndromes and CGD. Mammalian
      target of rapamycin (mTOR) inhibitors have been proven useful in autoimmune
      lymphoproliferative syndrome (ALPS) and in IPEX syndrome. Therapies reported to
      be potential use in case reports include abatacept in CTLA4 haploinsufficiency
      and LRBA deficiency, ruxolitinib in gain-of-function STAT1, tocilizumab in gain
      of-function STAT3 defect, mTOR inhibitors in PIK3CD activation, magnesium in XMEN
      syndrome, and pioglitazone in CGD. Treatment options of merit in human cell lines
      include interferon alpha and interferon beta in TLR3 and UNC-93B deficiencies,
      anti-interferon therapy in SAVI, and Rho-kinase inhibitors in TTC7A deficiency.
      Anti-IL17 agents have show efficacy in animal models of leukocyte adhesion defect
      (LAD) and ALPS. This topical review explores the use of various immunomodulators
      and other biological agents in the context of primary immunodeficiency and
      autoinflammatory diseases.

PMID- 27873168
TI  - Cardiac metastasis of clear cell thyroid cancer.

PMID- 27873169
TI  - Evaluation for the efficacy and safety of the crosser catheter as a CTO crossing
      device and a flossing device.
AB  - The Crosser catheter is a unique device that facilitates antegrade intraluminal
      recanalization by high-frequency vibration energy and cavitation. We used this
      device not only as a chronic total occlusion (CTO) crossing device, but also as a
      flossing device in stenotic lesions and we also evaluated the efficacy of this
      device when used with both the "Crosser preceding" and the "Guidewire preceding"
      in CTOs. Complications related to this device were investigated, too. We
      retrospectively analyzed a total of 90 consecutive patients with peripheral
      artery disease in the femoropopliteal artery and below-the-knee artery (BTA).
      Primary technical success was defined as the successful delivery of this device
      into the distal true lumen. Secondary technical success was defined as successful
      revascularization. The safety endpoints were events of angiographic
      complications, including the occurrence of detachment of the metal tip from the
      shaft, slow flow, dissections, and perforations. Overall primary technical
      success rate was 93.3% and the secondary technical success rate was 96.7%.
      Detachment and slow flow occurred 14.4 and 4.4%, respectively, with no
      occurrences of either dissection or perforation. A predictor of detachment was
      Proposed Peripheral Arterial Calcium Scoring System (PACSS) grade 4 (OR 14.6; CI
      1.26-168.5; P = 0.032). The Crosser catheter is useful not only as a CTO crossing
      device used with both the "Crosser preceding" and the "Guidewire preceding", but
      also as a flossing device in stenotic lesions. But we have to pay attention to
      complications related to the Crosser.

PMID- 27873170
TI  - Overcalling low-risk findings: grouped amorphous calcifications found at
      screening mammography associated with minimal cancer risk.
AB  - BACKGROUND: Because of the increasing availability of screening mammography and
      spread of information about its benefits, the incidence of early breast cancer
      has been increasing in Japan. However, screening mammography can result in
      overdiagnoses or false positives, causing in some subjects undergoing unnecessary
      invasive procedures. The current mammography guidelines recommend further
      investigation of subjects with grouped amorphous calcifications; this
      recommendation may have resulted in overdiagnoses or false positives. METHODS: We
      retrospectively reviewed the charts of patients who had undergone screening
      mammography in the screening unit of our institution from January 2011 to
      December 2012 and been found to have grouped amorphous calcifications. Of the 233
      such cases, 17 had been lost to follow-up, whereas whether the lesions were
      actually benign or malignant had been determined in the remaining 216 (92.7%).
      RESULTS: Six (2.8%) of 216 subjects with grouped amorphous calcifications were
      diagnosed as having malignancy and the remaining 210 (97.2%) as having benign
      lesions. Four of the six cases (1.9%) with malignancy had ductal carcinoma in
      situ and two (0.9%) 3 and 4 mm diameter invasive cancers of luminal type and
      nuclear grade 1. CONCLUSIONS: Grouped amorphous calcifications identified on
      screening mammography contribute minimally to detection of breast cancer and are
      not thought to be associated with any identifiable improvement in prognosis;
      present recommendations concerning this finding may result in false positives and
      overdiagnoses.

PMID- 27873172
TI  - Erratum to: Open Flow Microperfusion as a Dermal Pharmacokinetic Approach to
      Evaluate Topical Bioequivalence.

PMID- 27873171
TI  - Prognostic value of lower limb perfusion single-photon emission computed
      tomography-computed tomography in patients with lower limb atherosclerotic
      peripheral artery disease.
AB  - PURPOSE: The purpose of this study was to estimate the severity of the
      participants' lower limb ischemia by calculating the lower limb muscle-to
      background ratio (LMBR) using lower limb perfusion single-photon emission
      computed tomography-computed tomography (SPECT/CT) and to evaluate the prognostic
      value of LMBR in peripheral artery disease (PAD) patients. MATERIALS AND METHODS:
      This retrospective study consists of 38 patients with PAD (70 +/- 12 years) and
      observed over 1 year who were included in the analysis. All participants
      underwent lower limb perfusion SPECT/CT. LMBR was calculated by dividing
      counts/volume in lower limb muscle by mean counts/volume of background. All
      patients were divided into two groups based on their LMBR value and observed for
      the occurrence of a major adverse event (MAE). RESULTS: The high and low LMBR
      groups consisted of 26 and 12 patients, respectively. The median LMBR in the high
      group was 9.59 (6.11-11.87) while that in the low group was 4.35 (3.85-4.99). A
      significantly higher number of patients in the low LMBR group experienced MAE
      than in the high LMBR group (7 of 12 vs. 1 of 26, p < 0.001). CONCLUSION: This
      study demonstrated that the LMBR derived from lower limb perfusion SPECT/CT may
      have a high prognostic value in patients with PAD.

PMID- 27873173
TI  - Comparison of non-invasive peripheral venous saturations with venous blood co
      oximetry.
AB  - The estimation of venous oxygen saturations using photoplethysmography (PPG) may
      be useful as a noninvasive continuous method of detecting changes in regional
      oxygen supply and demand (e.g. in the splanchnic circulation). The aim of this
      research was to compare PPG-derived peripheral venous oxygen saturations directly
      with venous saturation measured from co-oximetry blood samples, to assess the
      feasibility of non-invasive local venous oxygen saturation. This paper comprises
      two similar studies: one in healthy spontaneously-breathing volunteers and one in
      mechanically ventilated anaesthetised patients. In both studies, PPG-derived
      estimates of peripheral venous oxygen saturations (SxvO2) were compared with co
      oximetry samples (ScovO2) of venous blood from the dorsum of the hand. The
      results were analysed and correlation between the PPG-derived results and co
      oximetry was tested for. In the volunteer subjects,moderate correlation (r =
      0.81) was seen between SxvO2 values and co-oximetry derived venous saturations
      (ScovO2), with a mean (+/-SD) difference of +5.65 +/- 14.3% observed between the
      two methods. In the anaesthetised patients SxvO2 values were only 3.81% lower
      than SpO2 and tended to underestimate venous saturation (mean difference = -2.67
      +/- 5.89%) while correlating weakly with ScovO2 (r = 0.10). The results suggest
      that significant refinement of the technique is needed to sufficiently improve
      accuracy to produce clinically meaningful measurement of peripheral venous oxygen
      saturation. In anaesthetised patients the use of the technique may be severely
      limited by cutaneous arteriovenous shunting.

PMID- 27873174
TI  - Prognostic value of exercise left ventricular end-systolic volume index in
      patients with asymptomatic aortic regurgitation: an exercise echocardiography
      study.
AB  - BACKGROUND: Surgical timing of chronic aortic regurgitation (AR) remains a matter
      of debate because of limited data. This study assessed the prognostic value of
      exercise echocardiography in asymptomatic AR. METHODS: This prospective study
      included 60 consecutive asymptomatic patients with isolated moderate or severe AR
      (mean regurgitant volume 56.7 +/- 11.8 ml) and preserved ejection fraction who
      underwent exercise echocardiography. The clinical outcomes were defined by the
      presence of major adverse cardiovascular events (MACE) and the indication for
      aortic valve replacement (AVR) with class I or IIa classification in the current
      guidelines. RESULTS: During the average follow-up of 731 days, 12 patients
      suffered from the clinical events, including two patients developing MACE (3%)
      and ten patients indicating for AVR (17%). No difference in left ventricular (LV)
      ejection fraction at rest was found between the patients with and without the
      clinical events. The indexed LV diameters and LV volumes were significantly
      dilated in the patients with the clinical events. The Cox proportional hazards
      regression analysis resulted that the exercise LV end-systolic volume index
      (LVESVi) was significantly associated with the clinical outcomes [hazard ratio,
      1.116; 95% CI (1.032-1.205); p = 0.006]. The Kaplan-Meier analysis showed that
      exercise LVESVi was clearly stratified the event-free survival. CONCLUSIONS:
      Exercise LVESVi might be an independent predictor of prognosis in patients with
      asymptomatic moderate or severe AR.

PMID- 27873177
TI  - Eculizumab treatment improved renal hemosiderosis in a patient with paroxysmal
      nocturnal hemoglobinuria.

PMID- 27873176
TI  - Palonosetron, aprepitant, and dexamethasone for prevention of nausea and vomiting
      after high-dose melphalan in autologous transplantation for multiple myeloma: A
      phase II study.
AB  - Chemotherapy-induced nausea and vomiting (CINV) is a significant side effect in
      multiple myeloma (MM) patients receiving high-dose melphalan treatment followed
      by autologous stem cell transplantation (ASCT). We evaluated the efficacy and
      safety of a triple antiemetic combination of palonosetron, aprepitant, and low
      dose dexamethasone in 24 MM patients who received melphalan conditioning (100
      mg/m2 on days 1-2) before ASCT (on day 4). Intravenous palonosetron (0.75 mg on
      day 1), oral aprepitant (125 mg on day 1; 80 mg on days 2-4), and intravenous
      dexamethasone (6.6 mg on days 1-4) were administered for prevention of CINV.
      Complete response (no emesis and no rescue antiemetic) and complete control (no
      emesis, no rescue antiemetic, and no more than mild nausea) rates were 75 and 68%
      during the overall phase (0-120 h), while they were 88 and 86% in the acute phase
      (0-48 h), 75 and 68% in the delayed phase (48-120 h), and 67 and 59% in the
      extended phase (120-168 h), respectively. There were no serious adverse events
      related to the antiemetic therapy. In conclusion, the three-antiemetic regimen
      consisting of palonosetron, aprepitant, and dexamethasone was safe and effective
      for controlling CINV due to high-dose melphalan treatment, especially during the
      delayed phase.

PMID- 27873175
TI  - Mobilization of human immature hematopoietic progenitors through combinatory use
      of bortezomib and immunomodulatory drugs.
AB  - Combination use of the proteasome inhibitor bortezomib and the immunomodulatory
      drugs lenalidomide or thalidomide has provided superior outcomes in multiple
      myeloma over their single use; however, these combinations can produce
      significant toxicities. Unexpectedly, we found a small but significant increase
      in the population of immature granulocytes and erythrocytes/megakaryocytes in
      peripheral blood in 16 of 22 patients (73%) treated with dexamethasone in
      combination with bortezomib and immunomodulatory drugs (triplet), but not in any
      of 25 patients treated with either bortezomib or immunomodulatory drugs with
      dexamethasone (doublet). These immature cells gradually increased to a peak level
      (mean 2.6% per white blood cells) with triplet therapy, and disappeared
      immediately after therapy cessation. The numbers of circulating CD34+ cells and
      colony-forming cells derived from peripheral blood mononuclear cells increased
      after triplet therapy compared with those in patients treated by either
      bortezomib or immunomodulatory drugs plus dexamethasone. Furthermore, triplet
      regimen downregulated the expression of CXCR4, a chemokine receptor essential for
      bone marrow retention, on CD34+ cells, suggesting an unexpected effect on normal
      hematopoietic stem/progenitor cells through the reduced interaction with the bone
      marrow microenvironment. Our observations suggest that combination use should be
      carefully evaluated to exert synergistic anti-myeloma effects while avoiding
      unexpected adverse events.

PMID- 27873178
TI  - Special Topic on Mental Health and Addiction.

PMID- 27873179
TI  - Oxycodone DETERx(r): A Novel Abuse-Deterrent, Extended-Release Analgesic Option
      for the Treatment of Patients with Chronic Pain.
AB  - BACKGROUND: Extended-release (ER) opioid analgesics are commonly used to provide
      safe and effective pain relief to treat pain severe enough to require around-the
      clock, long-term dosing. These ER opioid formulations usually contain more drug
      per dosage unit than immediate-release (IR) agents, and therefore bring with them
      challenges related to both opioid abuse and misuse, often through manipulation of
      the dosage form. Oxycodone DETERx(r) (Xtampza(r) ER, Collegium Pharmaceutical,
      Inc.) is a novel abuse-deterrent, ER formulation developed to deter common
      methods of manipulation. In addition to having abuse-deterrent properties,
      oxycodone DETERx was developed to provide alternative modes of administration for
      patients with chronic pain and difficulty swallowing. SCOPE: Using published
      articles, abstracts, and prescribing information, data supporting the use of
      oxycodone DETERx are reviewed. FINDINGS: Oxycodone DETERx was effective at
      reducing chronic pain in patients enrolled in a pivotal clinical trial, and had a
      tolerability profile expected of opioids. In addition to administration of the
      intact capsule, oxycodone DETERx can also be administered by sprinkling directly
      into the mouth from a dosing cup, onto soft foods, or through nasogastric or
      gastrostomy tubes, thus providing flexible dosing options for patients who have
      difficulty swallowing. In vitro studies demonstrated the reduced ability of
      oxycodone DETERx to be manipulated by common techniques used by abusers to defeat
      the ER characteristics or prepare the formulation for injection. Pharmacokinetic
      studies demonstrated that the ER characteristics of oxycodone DETERx are
      maintained if chewed or crushed. As a result, oxycodone DETERx is currently the
      only ER-formulated opioid without a boxed warning against crushing or chewing.
      Human abuse-potential studies conducted in a population of recreational opioid
      users demonstrated lower drug-liking scores for oxycodone DETERx administered
      intranasally and orally when compared with IR oxycodone. FUNDING: Collegium
      Pharmaceutical, Inc.

PMID- 27873180
TI  - Pledget-Armed Sutures Affect the Haemodynamic Performance of Biologic Aortic
      Valve Substitutes: A Preliminary Experimental and Computational Study.
AB  - Surgical aortic valve replacement is the most common procedure of choice for the
      treatment of severe aortic stenosis. Bioprosthetic valves are traditionally sewed
      in the aortic root by means of pledget-armed sutures during open-heart surgery.
      Recently, novel bioprostheses which include a stent-based anchoring system have
      been introduced to allow rapid implantation, therefore reducing the duration and
      invasiveness of the intervention. Different effects on the hemodynamics were
      clinically reported associated with the two technologies. The aim of this study
      was therefore to investigate whether the differences in hemodynamic performances
      are an effect of different anchoring systems. Two commercially available bio
      prosthetic aortic valves, one sewed-in with pledget-armed sutures and one rapid
      deployment, were thus tested in this study by means of a combined approach of
      experimental and computational tools. In vitro experiments were performed to
      evaluate the overall hydrodynamic performance under identical standard
      conditions; computational fluid dynamics analyses were set-up to explore local
      flow variations due to different design of the anchoring system. The results
      showed how the performance of cardiac valve substitutes is negatively affected by
      the presence of pledget-armed sutures. These are causing flow disturbances, which
      in turn increase the mean pressure gradient and decrease the effective orifice
      area. The combined approach of experiments and numerical simulations can be
      effectively used to quantify the detailed relationship between local fluid
      dynamics and overall performances associated with different valve technologies.

PMID- 27873181
TI  - Inhalable Ipratropium Bromide Particle Engineering with Multicriteria
      Optimization.
AB  - Spray-dried ipratropium bromide (IPB) microspheres for oral inhalation were
      engineered using Quality by Design. The interrogation of material properties,
      process parameters, and critical product quality attributes interplay enabled
      rational product design. A 27-3 screening design exhibited the Maillard reaction
      between L-leucine (LL) and lactose at studied outlet temperatures (OT) >130
      degrees C. A response surface custom design was used in conjunction with
      multicriteria optimization to determine the operating design space to achieve
      inhalable microparticles. Statistically significant predictive models were
      developed for volume median diameter (p = 0.0001, adjusted R 2  = 0.9938), span
      (p = 0.0278, adjusted R 2  = 0.7912), yield (p = 0.0020, adjusted R 2  = 0.9320),
      and OT (p = 0.0082, adjusted R 2  = 0.8768). An independent verification batch
      confirmed the model's predictive capability. The prediction and actual values
      were in good agreement. Particle size and span were 3.32 +/- 0.09 MUm and 1.71 +/
      0.18, which were 4.7 and 5.3% higher than the predicted values. The process
      yield was 50.3%, compared to the predicted value of 65.3%. The OT was 100 degrees
      C versus the predicted value of 105 degrees C. The label strength of IPB
      microparticles was 99.0 to 105.9% w/w suggesting that enrichment occurred during
      the spray-drying process. The present study can be utilized to initiate the
      design of the first commercial IPB dry powder inhaler.

PMID- 27873183
TI  - Interdisciplinary Oncology Education: a National Survey of Trainees and Program
      Directors in the United States.
AB  - Oncologists must have a strong understanding of collaborating specialties in
      order to deliver optimal cancer care. The objective of this study was to quantify
      current interdisciplinary oncology education among oncology training programs
      across the USA, identify effective teaching modalities, and assess communication
      skills training. Web-based surveys were sent to oncology trainees and program
      directors (PDs) across the USA on April 1, 2013 and October 8, 2013,
      respectively. Question responses were Yes/No, five-point Likert scales (1 = not
      at all, 2 = somewhat, 3 = moderately, 4 = quite, 5 = extremely), or free
      response. Respondents included the following (trainees/PDs): 254/55 medical
      oncology, 160/42 surgical oncology, 102/24 radiation oncology, and 41/20 hospice
      and palliative medicine (HPM). Trainees consistently reported lower rates of
      interdisciplinary education for each specialty compared with PDs as follows:
      medical oncology 57 vs. 77% (p < 0.01), surgical oncology 30 vs. 44% (p < 0.01),
      radiation oncology 70 vs. 89% (p < 0.01), geriatric oncology 19 vs. 30% (p <
      0.01), and HPM 55 vs. 74% (p < 0.01). The predominant teaching method used
      (lectures vs. rotations vs. tumor board attendance vs. workshop vs. other) varied
      according to which discipline was being taught. The usefulness of each teaching
      method was rated statistically different by trainees for learning about select
      disciplines. Furthermore, statistically significant differences were found
      between PDs and trainees for the perceived usefulness of several teaching
      modalities. This study highlights a deficiency of interdisciplinary education
      among oncology training programs in the USA. Efforts to increase
      interdisciplinary education opportunities during training may ultimately
      translate into improved collaboration and quality of cancer care.

PMID- 27873184
TI  - (+/-)-Evodiakine, A Pair of Rearranged Rutaecarpine-Type Alkaloids From Evodia
      rutaecarpa.
AB  - (+/-)-Evodiakine (1a and 1b), a pair of rearranged rutaecarpine-type alkaloids
      with an unprecedented 6/5/5/7/6 ring system, were isolated from the nearly ripe
      fruits of Evodia rutaecarpa. Separation of the enantiomers have been achieved by
      chiral HPLC column. The structures of (+/-)-evodiakine were unambiguously
      elucidated by 1D and 2D NMR spectra, mass spectrometry, and single-crystal X-ray
      diffraction. Their absolute configurations were determined by comparison of
      experimental and calculated electronic circular dichroism spectra. A hypothetical
      biogenetic pathway for (+/-)-evodiakine was also proposed. Compounds 1a, 1b, and
      the racemate (1) were tested for their cytotoxic and anti-inflammatory
      activities.

PMID- 27873182
TI  - Tau Imaging in Alzheimer's Disease Diagnosis and Clinical Trials.
AB  - In vivo imaging of the tau protein has the potential to aid in quantitative
      diagnosis of Alzheimer's disease, corroborate or dispute the amyloid hypothesis,
      and demonstrate biomarker engagement in clinical drug trials. A host of tau
      positron emission tomography agents have been designed, validated, and tested in
      humans. Several agents have characteristics approaching the ideal imaging tracer
      with some limitations, primarily regarding off-target binding. Dozens of clinical
      trials evaluating imaging techniques and several pharmaceutical trials have begun
      to integrate tau imaging into their protocols.

PMID- 27873185
TI  - Regressions during reading: The cost depends on the cause.
AB  - The direction and duration of eye movements during reading is predominantly
      determined by cognitive and linguistic processing, but some low-level oculomotor
      effects also influence the duration and direction of eye movements. One such
      effect is inhibition of return (IOR), which results in an increased latency to
      return attention to a target that has been previously attended (Posner & Cohen,
      Attention and Performance X: Control of Language Processes, 32, 531-556, 1984).
      Although this is a low level effect, it has also been found in the complex task
      of reading (Henderson & Luke, Psychonomic Bulletin & Review, 19(6), 1101-1107,
      2012; Rayner, Juhasz, Ashby, & Clifton, Vision Research, 43(9), 1027-1034, 2003).
      The purpose of the current study was to isolate the potentially different causes
      of regressive eye movements: to adjust for oculomotor error and to assist with
      comprehension difficulties. We found that readers demonstrated an IOR effect when
      regressions were caused by oculomotor error, but not when regressions were caused
      by comprehension difficulties. The results suggest that IOR is primarily
      associated with low-level oculomotor control of eye movements, and that
      regressive eye movements that are controlled by comprehension processes are not
      subject to IOR effects. The results have implications for understanding the
      relationship between oculomotor and cognitive control of eye movements and for
      models of eye movement control.

PMID- 27873186
TI  - Is nevtral NEUTRAL? Visual similarity effects in the early phases of written-word
      recognition.
AB  - For simplicity, contemporary models of written-word recognition and reading have
      unspecified feature/letter levels-they predict that the visually similar
      substituted-letter nonword PEQPLE is as effective at activating the word PEOPLE
      as the visually dissimilar substituted-letter nonword PEYPLE. Previous empirical
      evidence on the effects of visual similarly across letters during written-word
      recognition is scarce and nonconclusive. To examine whether visual similarity
      across letters plays a role early in word processing, we conducted two masked
      priming lexical decision experiments (stimulus-onset asynchrony = 50 ms). The
      substituted-letter primes were visually very similar to the target letters (u/v
      in Experiment 1 and i/j in Experiment 2; e.g., nevtral-NEUTRAL). For comparison
      purposes, we included an identity prime condition (neutral-NEUTRAL) and a
      dissimilar-letter prime condition (neztral-NEUTRAL). Results showed that the
      similar-letter prime condition produced faster word identification times than the
      dissimilar-letter prime condition. We discuss how models of written-word
      recognition should be amended to capture visual similarity effects across
      letters.

PMID- 27873187
TI  - Explaining the forgetting bias effect on value judgments: The influence of memory
      for a past test.
AB  - People often feel that information that was forgotten is less important than
      remembered information. Prior work has shown that participants assign higher
      importance to remembered information while undervaluing forgotten information.
      The current study examined two possible accounts of this finding. In three
      experiments, participants studied lists of words in which each word was randomly
      assigned a point value denoting the value of remembering the word. Following the
      presentation of each list participants engaged in a free recall test. After the
      presentation of all lists participants were shown each of the words they had
      studied and asked to recall the point value that was initially paired with each
      word. Experiment 1 tested a fluency-based account by presenting items for value
      judgments in a low-fluency or high-fluency format. Experiment 2 examined whether
      value judgments reflect attributions based on the familiarity of an item when
      value judgments are made. Finally, in Experiment 3, we evaluated whether
      participants believe that forgotten words are less important by having them judge
      whether an item was initially recalled or forgotten prior to making a value
      judgment. Manipulating the fluency of an item presented for judgment had no
      influence on value ratings (Experiment 1) and familiarity exerted a limited
      influence on value judgments (Experiment 2). More importantly, participants'
      value judgments appeared to reflect a theory that remembered information is more
      valuable than forgotten information (Experiment 3). Overall, the present work
      suggests that individuals may apply a theory about remembering and forgetting to
      retrospectively assess the value of information.

PMID- 27873188
TI  - Imagining the personal past: Episodic counterfactuals compared to episodic
      memories and episodic future projections.
AB  - Episodic counterfactuals are imagined events that could have happened, but did
      not happen, in a person's past. Such imagined past events are important aspects
      of mental life, affecting emotions, decisions, and behaviors. However, studies
      examining their phenomenological characteristics and content have been few. Here
      we introduced a new method to systematically compare self-generated episodic
      counterfactuals to self-generated episodic memories and future projections with
      regard to their phenomenological characteristics (e.g., imagery, emotional
      valence, and rehearsal) and content (e.g., reference to a cultural life script),
      and how these were affected by temporal distance (1 month, 1 year, 5+ years). The
      findings showed that the three types of events differed phenomenologically.
      First, episodic memories were remembered more easily, with more sensory details,
      and from a dominantly field perspective, as compared to both future projections
      and episodic counterfactuals. Second, episodic future projections were more
      positive, more voluntarily rehearsed, and more central to life story and identity
      than were both episodic memories and episodic counterfactuals. Third, episodic
      counterfactuals differed from both episodic memories and future projections by
      neither having the positivity bias of the future events nor the enhanced sensory
      details of the past events. Across all three event types, sensory details
      decreased, whereas importance, reference to a cultural life script, and
      centrality increased with increasing temporal distance. The findings show that
      imagined events are phenomenologically different from memories of experienced
      events, consistent with reality-monitoring theory, and that imagined future
      events are different from both actual and imagined past events, consistent with
      some theories of motivation.

PMID- 27873189
TI  - Learning multiple rules simultaneously: Affixes are more salient than
      reduplications.
AB  - Language learners encounter numerous opportunities to learn regularities, but
      need to decide which of these regularities to learn, because some are not
      productive in their native language. Here, we present an account of rule learning
      based on perceptual and memory primitives (Endress, Dehaene-Lambertz, & Mehler,
      Cognition, 105(3), 577-614, 2007; Endress, Nespor, & Mehler, Trends in Cognitive
      Sciences, 13(8), 348-353, 2009), suggesting that learners preferentially learn
      regularities that are more salient to them, and that the pattern of salience
      reflects the frequency of language features across languages. We contrast this
      view with previous artificial grammar learning research, which suggests that
      infants "choose" the regularities they learn based on rational, Bayesian criteria
      (Frank & Tenenbaum, Cognition, 120(3), 360-371, 2013; Gerken, Cognition, 98(3)B67
      B74, 2006, Cognition, 115(2), 362-366, 2010). In our experiments, adult
      participants listened to syllable strings starting with a syllable reduplication
      and always ending with the same "affix" syllable, or to syllable strings starting
      with this "affix" syllable and ending with the "reduplication". Both affixation
      and reduplication are frequently used for morphological marking across languages.
      We find three crucial results. First, participants learned both regularities
      simultaneously. Second, affixation regularities seemed easier to learn than
      reduplication regularities. Third, regularities in sequence offsets were easier
      to learn than regularities at sequence onsets. We show that these results are
      inconsistent with previous Bayesian rule learning models, but mesh well with the
      perceptual or memory primitives view. Further, we show that the pattern of
      salience revealed in our experiments reflects the distribution of regularities
      across languages. Ease of acquisition might thus be one determinant of the
      frequency of regularities across languages.

PMID- 27873190
TI  - Development of a Skill Acquisition Periodisation Framework for High-Performance
      Sport.
AB  - Unlike physical training, skill acquisition does not currently utilise
      periodisation to plan, monitor and evaluate programs. Development of a skill
      acquisition periodisation framework would allow for systematic investigation into
      the acute and longitudinal effectiveness of such interventions. Using the
      physical training literature as a reference point, a skill-training periodisation
      framework was developed for use in high-performance sport. Previous research
      undertaken in skill acquisition was used to provide support for the framework.
      The specificity, progression, overload, reversibility and tedium (SPORT) acronym
      was adopted. Each principle was then re-conceptualised so that it related to
      relevant skill acquisition principles. Methods for the measurement and analysis
      of each principle are provided and future directions for the longitudinal
      assessment of skill acquisition are discussed. The skill acquisition
      periodisation framework proposed in this study represents an opportunity for the
      principles relating to skill acquisition training to be measured in a systematic
      and holistic manner. This can also allow for a more sophisticated evaluation of
      the efficacy of longitudinal training programmes and interventions designed for
      sustained skill enhancement.

PMID- 27873192
TI  - On the Potential of Preemptive Genotyping Towards Preventing Medication-Related
      Adverse Events: Results from the South Korean National Health Insurance Database.

PMID- 27873193
TI  - Childcare and School Management Issues in Food Allergy.
AB  - PURPOSE OF REVIEW: The goal of this review is to characterize food allergy
      management and anaphylaxis in schools and assess current policies and level of
      preparedness of schools to recognize and treat anaphylaxis. RECENT FINDINGS: An
      increasing number of school-aged children have food allergies, and studies show
      that a significant number of school children with no known history of allergies
      will experience their first anaphylactic reaction at school. Stock-unassigned
      epinephrine auto-injectors are recommended in schools but not mandatory in most
      states, and therefore, epinephrine is not always available. Non-nursing staff
      members are sometimes administering epinephrine due to limitations in nurse
      staffing. Wide variations in staff training and lack of stock epinephrine leave
      many schools inadequately prepared to manage anaphylactic reactions. Emphasis
      should be placed not only on ensuring all schools have stock epinephrine but also
      on training a wider range of school staff members to minimize treatment delay
      with epinephrine and improve clinical outcomes.

PMID- 27873191
TI  - Effect of Exercise Training on Non-Exercise Physical Activity: A Systematic
      Review and Meta-Analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Many overweight and obese individuals use exercise when attempting to
      lose weight. However, the improvements in weight and body composition are often
      far less than expected. Levels of physical activity outside of the structured
      exercise program are believed to change and may be responsible for the
      unsuccessful weight loss. OBJECTIVE: The purpose of this meta-analysis was to
      provide a quantitative estimate of the change in non-exercise physical activity
      (NEPA) during exercise interventions. METHODS: All studies included in the meta
      analysis were peer-reviewed and published in English. Participants were
      randomized to a non-exercise comparison group or exercise training group with an
      intervention lasting >=2 weeks. NEPA was measured at baseline and at various
      times during the study. Hedges' d effect size (ES) was used to adjust for small
      sample bias, and random-effects models were used to calculate the mean ES and
      explore potential moderators. RESULTS: The cumulative results of 44 effects
      gathered from ten studies published between 1997 and 2015 indicated that NEPA did
      not change significantly during exercise training (ES = 0.02, 95% confidence
      interval [CI] -0.09 to 0.13; p = 0.723). Duration of the exercise session (beta =
      -0.0039), intervention length (beta = 0.0543), and an age * sex (beta = -0.0005)
      interaction indicated that the increase in NEPA may be attenuated in older women
      during exercise training and during shorter exercise interventions with longer
      sessions (all p < 0.005). CONCLUSION: On average, no statistically or clinically
      significant mean change in NEPA occurs during exercise training. However, session
      duration and intervention length, age, and sex should be accounted for when
      designing exercise programs to improve long-term sustainability and improve the
      likelihood of weight loss success, as the initial decrease in NEPA appears to
      dissipate with continued training.

PMID- 27873194
TI  - Lupin and Other Potentially Cross-Reactive Allergens in Peanut Allergy.
AB  - PURPOSE OF REVIEW: The presence of IgE cross-reactivity between peanut allergens
      and allergens from other legumes and tree nuts has been demonstrated, but the
      identification of the involved individual allergens is still limited. The aim of
      this review is to describe new allergenic findings, of potential relevance for
      cross-reactivity among peanut and lupin. RECENT FINDINGS: Seventeen allergens of
      peanut have been included in the official allergen nomenclature database to date.
      Lupin sensitization has been observed in 15-20% of individuals with known peanut
      allergy, The majority of lupin seed proteins are comprised of alpha-conglutins
      (legumin-like) and beta-conglutins (vicilin-like), and to a lesser extent gamma
      conglutins (vicilin-like) and delta-conglutins (2S albumins). Several molecules
      may fuel peanut-lupin cross-reactivity. Awareness among physicians and general
      public could avoid unexpected allergic reactions. However, these do not appear
      frequent and no data suggest a precautionary labelling of lupin in foods.

PMID- 27873196
TI  - The Expanding World of Small Molecule Microarrays.
AB  - Speed and throughput are vital ingredients for discovery driven, "-omics"
      research. The small molecule microarray (SMM) succeeds at delivering phenomenal
      screening throughput and versatility. The concept at the heart of the technology
      is elegant, yet simple: by presenting large collections of molecules in high
      density on a flat surface, one is able to interrogate all possible interactions
      with desired targets, in just a single step. SMMs have become established as the
      choice platform for screening, lead discovery, and molecular characterization.
      This introduction describes the principles governing microarray construction and
      use, focusing on practical challenges faced when conducting SMM experiments. It
      will explain the key design considerations and lay the foundation for the
      chapters that follow. (An earlier version of this chapter appeared in Small
      Molecule Microarrays: Methods and Protocols, published in 2010.).

PMID- 27873197
TI  - Novel Substrates for Microarrays.
AB  - In the microarray platform, the surface substrate is critical to the result
      quality in terms of signal consistency and detection sensitivity. Traditional
      substrates such as glass and nitrocellulose often entail complicated preparation
      processes such as the activation and functionalization of the reaction spots and
      surface blocking to prevent nonspecific molecule adsorption. In addition, coffee
      ring morphology of the spots is a common issue in the traditional substrates. To
      address these issues, we introduced a novel substrate based on fluorinated
      ethylene propylene (FEP) membrane for microarrays.

PMID- 27873195
TI  - Community structure of a sulfate-reducing consortium in lead-contaminated
      wastewater treatment process.
AB  - This study evaluated the capacity to remove lead by an indigenous consortium of
      five sulfate-reducing bacteria (SRB): Desulfobacterium autotrophicum,
      Desulfomicrobium salsugmis, Desulfomicrobium escambiense, Desulfovibrio vulgaris,
      and Desulfovibrio carbinolicus, using continuous moving bed biofilm reactor
      systems. Four continuous moving bed biofilm reactors (referred as R1-R4) were run
      in parallel for 40 days at lead loading rates of 0, 20, 30 and 40 mg l-1 day-1,
      respectively. The impact of lead on community structure of the SRB consortium was
      investigated by dsrB gene-based denaturing gradient gel electrophoresis (dsrB
      based DGGE), fluorescence in situ hybridization (FISH) and chemical analysis.
      These results indicated that D. escambiense and D. carbinolicus were dominant in
      all analyzed samples and played a key role in lead removal in R2 (20 mg l-1 day
      1) and R3 (30 mg l-1 day-1). However, in R4 (40 mg l-1 day-1), these two strains
      were barely detected by FISH and dsrB-based DGGE. As a result, SRB activity was
      severely affected by lead toxicity. High lead removal efficiencies of lead (99
      100%) were observed in R2 and R3 throughout the operation, whereas that in R4 was
      significantly decreased (91%) after 40 days of operation. This data strongly
      implied that the investigated SRB consortium might have potential application for
      lead removal. Moreover, to improve the efficiency of the lead treatment process,
      the lead loading rates below the inhibitory level to SRB activity should be
      selected.

PMID- 27873198
TI  - Fabrication of Bio-function-Preserved Saccharide Microarray Chips with Cyanuric
      Chloride as a Rotatable Linker.
AB  - Microarray-based saccharide chips possess an inherent property of high throughput
      but remain hard to use in practice due mainly to their fabrication problems,
      which have led to many strategies proposed but nearly none can immobilize small
      saccharides without losing their bio-affinity. Herein introduced is an easy
      strategy able to directly immobilize all intact saccharides on solid surface with
      excellent preservation of their molecular recognition ability. The core idea is
      to anchor a saccharide molecule on a universally rotatable molecular frame to
      free its spatial adjustment during molecular recognition process. This strategy
      can simply be realized by use of cyanuric chloride as a rotatable linker which
      offers three reactive chlorines pointing at 120 degrees . The first chlorine can
      readily react with hydroxyl groups at only 0-5  degrees C, enabling one to
      "plant" a layer of Y-shaped rotatable linker on hydroxyl-terminated surfaces.
      This facilitates the second chlorine on one of the upper "Y-branch" to react with
      saccharides at ca. 25  degrees C, a very convenient room temperature for
      practical manipulation. The third chlorine can further react with saccharides but
      at ca. 50  degrees C which is not too difficult to manipulate but commonly is not
      utilized. This chemical strategy has been exploited to dot various intact
      hydroxyl substances on either gold or glass surfaces, and the recognition ability
      of the anchored saccharides with their right lectins was validated to be well
      preserved according to surface plasmon resonance and/or laser-induced
      fluorescence imaging data. Furthermore the method is extendable to amines and
      other substances able to be hydroxylated and/or aminated.

PMID- 27873199
TI  - Fabrication of Carbohydrate Microarrays by Boronate Formation.
AB  - The interactions between soluble carbohydrates and/or surface displayed glycans
      and protein receptors are essential to many biological processes and cellular
      recognition events. Carbohydrate microarrays provide opportunities for high
      throughput quantitative analysis of carbohydrate-protein interactions. Over the
      past decade, various techniques have been implemented for immobilizing glycans on
      solid surfaces in a microarray format. Herein, we describe a detailed protocol
      for fabricating carbohydrate microarrays that capitalizes on the intrinsic
      reactivity of boronic acid toward carbohydrates to form stable boronate diesters.
      A large variety of unprotected carbohydrates ranging in structure from simple
      disaccharides and trisaccharides to considerably more complex human milk and
      blood group (oligo)saccharides have been covalently immobilized in a single step
      on glass slides, which were derivatized with high-affinity boronic acid ligands.
      The immobilized ligands in these microarrays maintain the receptor-binding
      activities including those of lectins and antibodies according to the structures
      of their pendant carbohydrates for rapid analysis of a number of carbohydrate
      recognition events within 30 h. This method facilitates the direct construction
      of otherwise difficult to obtain carbohydrate microarrays from underivatized
      glycans.

PMID- 27873200
TI  - Clickable Polymeric Coating for Glycan Microarrays.
AB  - The interaction of carbohydrates with a variety of biological targets, including
      antibodies, proteins, viruses, and cells are of utmost importance in many aspects
      of biology. Glycan microarrays are increasingly used to determine the binding
      specificity of glycan-binding proteins. In this study, a novel microarray support
      is reported for the fabrication of glycan arrays that combines the higher
      sensitivity of a layered Si-SiO2 surface with a novel polymeric coating easily
      modifiable by subsequent click reaction. The alkyne-containing copolymer,
      adsorbed from an aqueous solution, produces a coating by a single step procedure
      and serves as a soft, tridimensional support for the oriented immobilization of
      carbohydrates via azide/alkyne Cu (I) catalyzed "click" reaction. The advantages
      of a functional 3D polymer coating making use of a click chemistry immobilization
      are combined with the high fluorescence sensitivity and superior signal-to-noise
      ratio of a Si-SiO2 substrate. The proposed approach enables the attachment of
      complex sugars on a silicon oxide surface by a method that does not require
      skilled personnel and chemistry laboratories.

PMID- 27873201
TI  - A Versatile Microarray Immobilization Strategy Based on a Biorthogonal Reaction
      Between Tetrazine and Trans-Cyclooctene.
AB  - Given its increasing importance in transforming biomedical research in recent
      years, microarray technology has become highly popular as a powerful screening
      platform in detecting biomolecule interactions, discovering new inhibitors, and
      identifying biomarkers as well as diagnosing disease. The success of microarray
      technology in various biological applications is highly dependent on the
      accessibility, the functionality, and the density of the surface bound
      biomolecules. Therefore, compound immobilization represents a critical step for
      the successful implementation of microarray screening. Herein we describe a fast
      and site-specific microarray immobilization approach by using trans-cyclooctene
      tetrazine ligation. This approach not only ensures fast immobilization and
      uniform display of biomolecules, but also allows the optimum orientation of
      biomolecules after immobilization. All these excellent properties facilitate
      subsequent interactions of the biomolecules and their interacting partners during
      the screening process. We envision that the immobilization strategy described
      here can find useful applications in many other microarray related studies.

PMID- 27873202
TI  - Label-Free Sensing on Microarrays.
AB  - Microarrays of biological molecules such as DNAs, proteins, carbohydrates, and
      small molecules provide a high-throughput platform for screening tens of
      thousands of biomolecular interactions simultaneously, facilitating the
      functional characterization of these biomolecules in areas of genomics,
      proteomics, glycomics, and cytomics. Routinely, analysis of binding reactions
      between solution-phased probes and surface-immobilized targets involves some
      kinds of fluorescence-based detection methods. Even though these methods have
      advantages of high sensitivity and wide dynamic range, labeling probes and/or
      targets inevitably changes their innate properties and in turn affects probe
      target interactions in often uncharacterized ways. Therefore, in recent years,
      various label-free sensing technologies have been developed for characterizing
      biomolecular interactions in microarray format. These biosensors, to a certain
      extent, take the place of fluorescent methods by providing a comparable
      sensitivity as well as retaining the conformational and functional integrality of
      biomolecules to be investigated. More importantly, some of these biosensors are
      capable of real-time monitoring probe-target interactions, providing the binding
      affinities of these reactions. Using label-free biosensors in microarrays has
      become a current trend in developing high-throughput screening platforms for drug
      discoveries and applications in all areas of "-omics." This article is aimed to
      provide principles and recent developments in label-free sensing technologies
      applicable to microarrays, with special attentions being paid to surface plasmon
      resonance microscopy and oblique-incidence reflectivity difference microscopy.

PMID- 27873203
TI  - Optical Microscopy for Detecting Binding on Small Molecule Microarrays.
AB  - Small molecule microarrays (SMMs) have revolutionized parallel screening of
      multiple biological interactions. SMMs are a high-throughput technique for
      simultaneous detection of up to thousands of biological interactions.
      Conventional detection technique employed in SMMs is fluorescence spectroscopy.
      However, the possibility of fluorescent labels affecting the binding properties
      of small molecules drives the development of label-free screening techniques.
      Here, we describe two label-free detection techniques using optical microscopy
      for the detection of binding on SMMs. The first optical detection technique
      ellipsometry, and more specifically, oblique incidence reflectivity difference to
      study the kinetics of the association between small molecule targets and protein
      probes is discussed. Then, we describe another optical detection technique
      surface plasmon resonance microscopy. The sample preparation steps and protocols
      of the two techniques to study the interactions between SMMs and their protein
      targets are elaborated in great detail.

PMID- 27873204
TI  - Array-on-Array Strategy For Activity-Based Enzyme Profiling.
AB  - We describe a novel array on array strategy intended to enhance the throughput of
      enzymatic activity screening using microarrays. This strategy consists of
      spotting a first array with large droplets of enzymes with varying concentrations
      and subsequently spotting a second array with small droplets of fluorogenic
      substrate on top of the enzyme array. By varying the array on array spotting
      patterns of different classes of enzyme (e.g., proteases, phosphatases, kinases)
      and their corresponding fluorogenic substrates, we have the unprecedented ability
      for testing enzymes and mixed samples in a multiplexed fashion within a single
      microarray slide. This new approach enables rapid enzyme characterization
      building upon a one enzyme on one slide droplet-based screening concept
      previously established.

PMID- 27873205
TI  - Protein-Protein Interaction Inhibitors of BRCA1 Discovered Using Small Molecule
      Microarrays.
AB  - Microarray screening technology has transformed the life sciences arena over the
      last decade. The platform is widely used in the area of mapping interaction
      networks, to molecular fingerprinting and small molecular inhibitor discovery.
      The technique has significantly impacted both basic and applied research. The
      microarray platform can likewise enable high-throughput screening and discovery
      of protein-protein interaction (PPI) inhibitors. Herein we demonstrate the
      application of microarray-guided PPI inhibitor discovery, using human BRCA1 as an
      example. Mutations in BRCA1 have been implicated in ~50 % of hereditary breast
      cancers. By targeting the (BRCT)2 domain, we showed compound 15a and its prodrug
      15b inhibited BRCA1 activities in tumor cells. Unlike previously reported peptide
      based PPI inhibitors of BRCA1, the compounds identified could be directly
      administered to tumor cells, thus making them useful in targeting BRCA1/PARP
      related pathways involved in DNA damage and repair response, for cancer therapy.

PMID- 27873206
TI  - Discovery of RNA Binding Small Molecules Using Small Molecule Microarrays.
AB  - New methods to identify RNA-binding small molecules open yet unexplored
      opportunities for the pharmacological modulation of RNA-driven biology and
      disease states. One such approach is the use of small molecule microarrays
      (SMMs). Typically, SMMs are generated by spatially arraying and covalently
      linking a library of small molecules to a glass surface. Next, incubation of the
      arrays with a fluorescently labeled RNA reveals binding interactions that are
      detected upon slide imaging. The relative ease with which SMMs are manufactured
      enables the screening of multiple oligonucleotides in parallel against tens of
      thousands of small molecules, providing information about both binding and
      selectivity of identified RNA-small molecule interactions. This approach is
      useful for screening a broad variety of structurally and functionally diverse
      RNAs. Here, we present a general method for the preparation and use of SMMs to
      rapidly identify small molecules that selectively bind to an RNA of interest.

PMID- 27873207
TI  - Profiling Phosphopeptide-Binding Domain Recognition Specificity Using Peptide
      Microarrays.
AB  - Cellular organization and response to internal and external stimuli are mediated
      by an intricate web of protein interactions. Some of these interactions are
      regulated by covalent posttranslational modifications such as phosphorylation and
      acetylation. These modifications can change the chemical nature of the
      interaction interfaces and modulate the binding affinity of the interacting
      partners. In signal transduction, the most frequent modification is reversible
      phosphorylation of tyrosine, serine or threonine residues. Protein
      phosphorylation may modulate the activity of enzymes by modifying their
      conformation, or regulate the formation of complexes by creating docking sites to
      recruit downstream effectors. Families of modular domains, such as SH2, PTB, and
      14-3-3, act as "readers" of the modification event. Specificity between closely
      related domains of the same family is mediated by the chemical properties of the
      domain binding surface that, aside from offering a hydrophilic pocket for the
      phosphorylated residue, shows preference for specific sequences. Although the
      protein structure and the cell context are also important to ensure specificity,
      the amino acid sequence flanking the phosphorylation site defines the accuracy of
      the recognition process, and it is therefore essential to define the binding
      specificity of phosphopeptide binding domains in order to understand and to infer
      the interaction web mediated by phosphopeptides. Methods commonly used to
      discover new interactions (such as yeast two hybrid and phage display) are not
      suited to study interactions with phosphorylated proteins. On the other hand,
      peptide arrays are a powerful approach to precisely identify the binding
      preference of phosphopeptide recognition domains. Here we describe a detailed
      protocol to assemble arrays of hundreds to thousands phospho-peptides and to
      screen them with any modular domain of interest.

PMID- 27873208
TI  - Validation Procedure for Multiplex Antibiotic Immunoassays Using Flow-Based
      Chemiluminescence Microarrays.
AB  - Small molecules like antibiotics or other pharmaceuticals can be detected and
      quantified, among others, with indirect competitive immunoassays. With regard to
      multiplex quantification, these tests can be performed as chemiluminescence
      microarray immunoassays, in which, in principle, the analyte in the sample and
      the same substance immobilized on the chip surface compete for a limited number
      of specific antibody binding sites. The amount of the specific primary antibody
      that has been bound to the surface is visualized by means of a chemiluminescence
      reaction.Validated quantitative confirmatory methods for the detection of
      contaminants, for example drug residues, in food samples usually comprise
      chromatographic analysis and spectrometric detection, e.g., HPLC-MS, GC-MS, or GC
      with electron capture detection. Here, we describe a validation procedure
      (according to the Commission Decision of the European Communities 2002/657/EC)
      for multiplex immunoassays performed as flow-through chemiluminescence
      microarrays, using the example of a small molecule microarray for the
      simultaneous detection of 13 antibiotics in milk. By this means, we suggest to
      accept multianalyte immunoassays as confirmatory methods as well, to benefit from
      the advantages of a fast automated method that does not need any pretreatment of
      the sample. The presented microarray chip is regenerable, so an internal
      calibration is implemented. Therefore, the analytical results are highly precise,
      combined with low costs (the aim for commercialization is less than 1 ? per
      analyte per sample, this is significantly less than HPLC-MS).

PMID- 27873209
TI  - Large-Scale Interaction Profiling of Protein Domains Through Proteomic Peptide
      Phage Display Using Custom Peptidomes.
AB  - Protein-protein interactions are essential to cellular functions and signaling
      pathways. We recently combined bioinformatics and custom oligonucleotide arrays
      to construct custom-made peptide-phage libraries for screening peptide-protein
      interactions, an approach we call proteomic peptide-phage display (ProP-PD). In
      this chapter, we describe protocols for phage display for the identification of
      natural peptide binders for a given protein. We finally describe deep sequencing
      for the analysis of the proteomic peptide-phage display.

PMID- 27873210
TI  - Synthetic Glycan Microarrays.
AB  - Structurally diverse glycans are expressed by all animate beings and exert
      diverse biological functions through specific interactions with glycan binding
      proteins (GBPs). In humans, glycan-GBP interactions are implicated in many
      disease-relevant processes in development, infection and immune response to
      bacterial and viral pathogens. Recent progress in chemical synthesis, including
      automated glycan assembly, has facilitated access to complex glycans that cannot
      be isolated from biological material. Glycan immobilization on microarrays allows
      rapid, multiplexed glycan-GBP interaction studies to reveal biological functions.
      Synthetic glycan microarrays have enabled, for instance, the identification of
      glycan ligands for lectins, the definition of vaccine antigens, revealed viral
      glycan receptors and can serve as diagnostic tools for human disease. Here, we
      describe the methods to fabricate custom glycan microarrays that are used to
      examine glycan-GBP binding specificities. Conjugation-ready synthetic glycans are
      covalently attached to microarray surfaces through nucleophilic linker moieties.
      Microarrays are incubated with GBPs, and binding events are quantitatively
      detected by fluorescent signals. These methods are readily adaptable to a
      multitude of purposes from basic research to biomedical applications.

PMID- 27873211
TI  - Screening Mammalian Cells on a Hydrogel: Functionalized Small Molecule
      Microarray.
AB  - Mammalian cell-based microarray technology has gained wide attention, for its
      plethora of promising applications. The platform is able to provide simultaneous
      information on multiple parameters for a given target, or even multiple target
      proteins, in a complex biological system. Here we describe the preparation of
      mammalian cell-based microarrays using selectively captured of human prostate
      cancer cells (PC-3). This platform was then used in controlled drug release and
      measuring the associated drug effects on these cancer cells.

PMID- 27873212
TI  - HABP2 G534E variation in familial non-medullary thyroid cancer: an Italian
      series.
AB  - INTRODUCTION: Thyroid cancer may have a familial predisposition and may occur in
      the context of hereditary syndromes or as isolated tumor. Recently, the G534E
      variant in the HABP2 gene has been suggested as causative mutation for familial
      thyroid cancer, but other studies gave contradictory results. METHODS: We have
      analyzed the G534E variant in an Italian series of 63 familial thyroid cancer
      patients and 41 unaffected family members with end-point PCR, DHPLC and direct
      sequencing. RESULTS: All samples analyzed displayed a pattern typical of the
      homozygous wild type revealing the absence of the G534E variant. CONCLUSION: In
      this study, HABP2 G534E variant is not correlated with the familial form of PTC.

PMID- 27873213
TI  - Is management of hyperglycaemia in acute phase stroke still a dilemma?
AB  - INTRODUCTION: Close monitoring of blood glucose levels during the immediate post
      acute stroke phase is of great clinical value, as there is evidence that the risk
      of neurological deterioration is associated with both hyper- and hypoglycaemia.
      The aim of this review paper is to summarise the evidence on post-stroke blood
      glucose management and its impact on clinical outcomes, during the early post
      acute stage. FINDINGS: Post-stroke hyperglycaemia has been associated with
      increased cerebral oedema, haemorrhagic transformation, lower likelihood of
      recanalisation and deteriorating neurological state. Thus, hyperglycaemia during
      an acute stroke may result in poorer clinical outcomes, infarct progression, poor
      functional recovery and increased mortality rates. Although hypoglycaemia may
      also lead to poorer outcomes via further brain injury, it can be readily reversed
      by glucose administration. In most patients, the goal of regular treatment is
      euglycaemia and for acute-stroke patients, a reasonable approach is to target
      control of glucose level at 100-150 mg/dL. CONCLUSION: Both hypoglycaemia and
      hyperglycaemia may lead to further brain injury and clinical deterioration; that
      is the reason these conditions should be avoided after stroke. Yet, when
      correcting hyperglycaemia, great care should be taken not to switch the patient
      into hypoglycaemia, and subsequently aggressive insulin administration treatment
      should be avoided. Early identification and prompt management of hyperglycaemia,
      especially in acute ischaemic stroke, is recommended. Although the appropriate
      level of blood glucose during acute stroke is still debated, a reasonable
      approach is to keep the patient in a mildly hyperglycaemic state, rather than
      risking hypoglycaemia, using continuous glucose monitoring.

PMID- 27873214
TI  - Risk Factors for Non-Therapeutic Initial Steady-State Vancomycin Trough
      Concentrations in Children and Adolescents Receiving High Empiric Doses of
      Intravenous Vancomycin.
AB  - BACKGROUND: Achieving vancomycin troughs of 15-20 MUg/mL remains challenging in
      children. Our objective was to identify risk factors associated with non
      therapeutic initial vancomycin troughs in children. METHODS: We conducted a
      retrospective cohort study of children who received intravenous vancomycin with
      at least one initial steady-state trough obtained. Patients who achieved
      therapeutic troughs (15-20 MUg/mL in the 20-mg/kg/dose sub-cohort and 10-15
      MUg/mL in the 15-mg/kg/dose sub-cohort) were compared with those with
      subtherapeutic troughs (<15 and <10 MUg/mL, respectively) and supratherapeutic
      troughs (>20 and >15 MUg/mL, respectively) separately to determine risk factors
      associated with non-therapeutic troughs. RESULTS: A total of 153 vancomycin
      courses in 140 patients met study eligibility criteria. Of 45 patients who
      received 20 mg/kg/dose of empiric vancomycin, 60, 16, and 24% were
      subtherapeutic, therapeutic, and supratherapeutic, respectively. Each 10
      mL/min/1.73 m2 increase in initial creatinine clearance (CrCl) was associated
      with a 47% increase in the odds of an initial subtherapeutic trough (adjusted
      odds ratio [aOR] 1.47; 95% CI 0.98-2.22). Of 108 patients who received 15
      mg/kg/dose of empiric vancomycin, 62, 19, and 19% were subtherapeutic,
      therapeutic, and supratherapeutic, respectively. Each 10-mL/min/1.73 m2 increase
      in initial CrCl was associated with an 18% increase in the odds of an initial
      subtherapeutic trough (aOR 1.18; 95% CI 1.02-1.37). CONCLUSION: Achieving
      vancomycin troughs of 15-20 MUg/mL for severe Gram-positive infections continues
      to be challenging in children, even at higher empiric doses of 20 mg/kg/dose IV
      every 6-8 h. Children with higher initial CrCls are particularly susceptible to
      subtherapeutic initial steady-state vancomycin troughs.

PMID- 27873215
TI  - Current and Future Treatment Approaches in Transthyretin Familial Amyloid
      Polyneuropathy.
AB  - OPINION STATEMENT: Treatment of transthyretin familial amyloid polyneuropathy
      (TTR FAP) must be tailored to disease stage. Patients with early stage disease
      (i.e., without major impairment in walking ability), especially younger patients,
      should be referred as soon as possible for liver transplantation (LT) in the
      absence of major comorbid conditions. LT remains the most effective treatment
      option to date and should be offered to these patients as early as possible.
      Bridging therapy with an oral TTR stabilizer (tafamidis or diflunisal, according
      to local access to these treatments) should be started as soon as the diagnosis
      of TTR FAP is established. Early stage patients who do not wish to or have
      contraindications to LT should be treated with an oral TTR stabilizer or get
      access to the newly developed therapeutic options (IONIS TTR-Rx, patisiran,
      doxycycline/TUDCA). Late stage patients (presenting with significant walking
      impairment) are usually older and notoriously difficult to treat. They should be
      offered an oral TTR stabilizer but are not candidates for LT due to a significant
      rate of perioperative complications and increased risk of progressive
      neurological and especially cardiac disease despite LT. Access to the different
      therapies in development should also be considered depending on respective
      inclusion and exclusion criteria. The abovementioned treatment options were
      mostly validated in Val30Met mutation patients, but should also be offered to non
      Val30Met patients, although mortality rates after LT are higher in these
      patients. Treatment decisions should be made on an individual basis. Screening
      for heart, eye, and renal involvement is mandatory for every patient at disease
      diagnosis and regularly thereafter, even in transplanted patients. Symptomatic
      treatment should be offered as needed, as well as genetic counseling to at-risk
      family members. Asymptomatic mutation carriers should benefit from regular
      screening for early symptoms of disease. Current therapeutic management of TTR
      FAP will hopefully be changed in the near future with data from the ongoing phase
      2/3 studies testing the TTR gene silencing agents. In the longer term, it is
      likely that combined therapeutic approaches will be necessary to reverse the
      disease process.

PMID- 27873216
TI  - Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass
      Spectrometry Imaging.
AB  - Metabolites can be an important read-out of disease. The identification and
      validation of biomarkers in the cancer metabolome that can stratify high-risk
      patients is one of the main current research aspects. Mass spectrometry has
      become the technique of choice for metabolomics studies, and mass spectrometry
      imaging (MSI) enables their visualization in patient tissues. In this study, we
      used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33
      high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma,
      myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed.
      Metabolite MSI data were obtained from sections of fresh frozen tissue specimens
      with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity
      using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by
      expert pathologists resulted in tumor-specific metabolite signatures, which were
      then tested for association with patient survival. Metabolite signals with
      significant clinical value were further validated and identified by high mass
      resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three
      metabolite signals were found to correlate with overall survival (m/z 180.9436
      and 241.0118) and metastasis-free survival (m/z 160.8417). FTICR-MSI identified
      m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.
      Graphical Abstract ?.

PMID- 27873217
TI  - A Retrospective Evaluation of the Use of Mass Spectrometry in FDA Biologics
      License Applications.
AB  - The characterization sections of biologics license applications (BLAs) approved
      by the United States Food and Drug Administration (FDA) between 2000 and 2015
      were investigated to examine the extent of the use of mass spectrometry. Mass
      spectrometry was found to be integral to the characterization of these
      biotherapeutics. Of the 80 electronically submitted monoclonal antibody and
      protein biotherapeutic BLAs included in this study, 79 were found to use mass
      spectrometric workflows for protein or impurity characterization. To further
      examine how MS is being used in successful BLAs, the applications were filtered
      based on the type and number of quality attributes characterized, the mass
      spectrometric workflows used (peptide mapping, intact mass analysis, and cleaved
      glycan analysis), the methods used to introduce the proteins into the gas phase
      (ESI, MALDI, or LC-ESI), and the specific types of instrumentation used. Analyses
      were conducted over a time course based on the FDA BLA approval to determine if
      any trends in utilization could be observed over time. Additionally, the
      different classes of protein-based biotherapeutics among the approved BLAs were
      clustered to determine if any trends could be attributed to the specific type of
      biotherapeutic. Graphical Abstract ?.

PMID- 27873218
TI  - Characterization of Glycan Structures of Chondroitin Sulfate-Glycopeptides
      Facilitated by Sodium Ion-Pairing and Positive Mode LC-MS/MS.
AB  - Purification and liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      characterization of glycopeptides, originating from protease digests of
      glycoproteins, enables site-specific analysis of protein N- and O-glycosylations.
      We have described a protocol to enrich, hydrolyze by chondroitinase ABC, and
      characterize chondroitin sulfate-containing glycopeptides (CS-glycopeptides)
      using positive mode LC-MS/MS. The CS-glycopeptides, originating from the Bikunin
      proteoglycan of human urine samples, had DeltaHexAGalNAcGlcAGalGalXyl-O-Ser
      hexasaccharide structure and were further substituted with 0-3 sulfate and 0-1
      phosphate groups. However, it was not possible to exactly pinpoint sulfate
      attachment residues, for protonated precursors, due to extensive fragmentation of
      sulfate groups using high-energy collision induced dissociation (HCD). To
      circumvent the well-recognized sulfate instability, we now introduced Na+ ions to
      form sodiated precursors, which protected sulfate groups from decomposition and
      facilitated the assignment of sulfate modifications. Sulfate groups were
      pinpointed to both Gal residues and to the GalNAc of the hexasaccharide
      structure. The intensities of protonated and sodiated saccharide oxonium ions
      were very prominent in the HCD-MS2 spectra, which provided complementary
      structural analysis of sulfate substituents of CS-glycopeptides. We have
      demonstrated a considerable heterogeneity of the bikunin CS linkage region. The
      realization of these structural variants should be beneficial in studies aimed at
      investigating the importance of the CS linkage region with regards to the
      biosynthesis of CS and potential interactions to CS binding proteins. Also, the
      combined use of protonated and sodiated precursors for positive mode HCD
      fragmentation analysis will likely become useful for additional classes of
      sulfated glycopeptides. Graphical Abstract ?.

PMID- 27873220
TI  - Examining how and why to Engage Practitioners from across the Learning Landscape
      in the Research Enterprise: Proposal for Phronetic Research on Education.
AB  - Educational practitioners are often reluctant, if not actively resistant, to
      their participation in production and consumption of educational research. Based
      on my research experience with educational practitioners, I try to deconstruct
      this phenomenon using dialogic Bakhtinian and Aristotelian sociocultural
      frameworks. I consider two major related breakdowns in the educational practice:
      1) a lack of self-correcting process in the educational practice, while reliance
      on accountability policy to achieve the practice quality, and 2) a breakdown
      between educational research and educational practice. I argue that the first
      breakdown is caused by viewing teaching as poiesis, aiming at preset curricular
      endpoints, and not as praxis, critically defining its own values, goals, and
      virtues. As to the second breakdown, I argue that current mainstream and even
      innovative research is defined through the techne and episteme ways of knowing,
      which correspond to a poiesic vision of educational practice. I suggest that
      educational practice primarily involves the phronetic and sophic ways of knowing,
      which correspond to a praxis vision of educational practice. I describe phronetic
      research of teaching through a case of my students, preservice teachers, working
      on revisions of their lessons that they conducted at an urban afterschool
      program. Finally, I consider recommendations for institutional support for
      phronetic research on teaching.

PMID- 27873221
TI  - One Size May Not Fit All: How Obesity Among Mexican-Origin Youth Varies by
      Generation, Gender, and Age.
AB  - Immigrants' health (dis)advantages are increasingly recognized as not being
      uniform, leading to calls for studies investigating whether immigrant health
      outcomes are dependent on factors that exacerbate health risks. We answer this
      call, considering an outcome with competing evidence about immigrants'
      vulnerability versus risk: childhood obesity. More specifically, we investigate
      obesity among three generations of Mexican-origin youth relative to one another
      and to U.S.-born whites. We posit that risk is dependent on the intersection of
      generational status, gender, and age, which all influence exposure to U.S.
      society and weight concerns. Analyses of National Health and Nutrition
      Examination Studies (NHANES) data suggest that accounting for ethnicity and
      generation alone misses considerable gender and age heterogeneity in childhood
      obesity among Mexican-origin and white youth. For example, second-generation boys
      are vulnerable to obesity, but the odds of obesity for first-generation girls are
      low and on par with those of white girls. Findings also indicate that age
      moderates ethnic/generational differences in obesity among boys but not among
      girls. Overall, ethnic/generational patterns of childhood obesity do not conform
      to a "one size fits all" theory of immigrant health (dis)advantage, leading us to
      join calls for more research considering how immigrants' characteristics and
      contexts differentially shape vulnerability to disease and death.

PMID- 27873222
TI  - Young Children's Developmental Ecologies and Kindergarten Readiness.
AB  - Children enter the crucial transition to school with sociodemographic disparities
      firmly established. Domain-specific research (e.g., on poverty and family
      structure) has shed light on these disparities, but we need broader
      operationalizations of children's environments to explain them. Building on
      existing theory, this study articulates the concept of developmental ecology
      those interrelated features of a child's proximal environment that shape
      development and health. Developmental ecology links structural and demographic
      factors with interactional, psychological, and genetic factors. Using the Early
      Childhood Longitudinal Study, Birth Cohort (ECLS-B), this study conducts latent
      class analyses to identify how 41 factors from three domains-namely, household
      resources, health risks, and ecological changes-cluster within children as four
      overarching developmental ecologies. Because it documents how numerous factors co
      occur within children, this method allows an approximation of their lived
      environments. Findings illuminate powerful relationships between race/ethnicity,
      parental age, socioeconomic background, and nativity and a child's developmental
      ecology, as well as associations between developmental ecology and kindergarten
      cognition, behavior, and health. Developmental ecology represents a major pathway
      through which demographic characteristics shape school readiness. Because
      specific factors have different implications depending on the ecologies in which
      they are embedded, findings support the usefulness of a broad ecological
      approach.

PMID- 27873223
TI  - Assimilation and Health: Evidence From Linked Birth Records of Second- and Third
      Generation Hispanics.
AB  - This study explores the effects of assimilation on the health of Hispanics in the
      United States, using ethnic intermarriage as a metric of acculturation. I exploit
      a unique data set of linked confidential use birth records in California and
      Florida from 1970-2009. The confidential data allow me to link mothers giving
      birth in 1989-2009 to their own birth certificate records in 1970-1985 and to
      identify second-generation siblings. Thus, I can analyze the relationship between
      the parental exogamy of second-generation Hispanic women and the birth outcomes
      of their offspring controlling for grandmother fixed effects as well as
      indicators for second generation's birth weight. Despite their higher
      socioeconomic status, third-generation children of second-generation intermarried
      Hispanic women are more likely to have poor health at birth, even after I account
      for second-generation health at birth and employ only within-family variations in
      the extent of assimilation. I find that a second-generation Hispanic woman
      married to a non-Hispanic man is 9 % more likely to have a child with low birth
      weight relative to a second-generation woman married to another Hispanic. These
      results largely reflect the higher incidence of risky behaviors (e.g., smoking
      during pregnancy) among intermarried Hispanic women.

PMID- 27873219
TI  - Immortalization of primary microglia: a new platform to study HIV regulation in
      the central nervous system.
AB  - The major reservoirs for HIV in the CNS are in the microglia, perivascular
      macrophages, and to a lesser extent, astrocytes. To study the molecular events
      controlling HIV expression in the microglia, we developed a reliable and robust
      method to immortalize microglial cells from primary glia from fresh CNS tissues
      and commercially available frozen glial cells. Primary human cells, including
      cells obtained from adult brain tissue, were transformed with lentiviral vectors
      expressing SV40 T antigen or a combination of SVR40 T antigen and hTERT. The
      immortalized cells have microglia-like morphology and express key microglial
      surface markers including CD11b, TGFbetaR, and P2RY12. Importantly, these cells
      were confirmed to be of human origin by sequencing. The RNA expression profiles
      identified by RNA-seq are also characteristic of microglial cells. Furthermore,
      the cells demonstrate the expected migratory and phagocytic activity, and the
      capacity to mount an inflammatory response characteristic of primary microglia.
      The immortalization method has also been successfully applied to a wide range of
      microglia from other species (macaque, rat, and mouse). To investigate different
      aspects of HIV molecular regulation in CNS, the cells have been superinfected
      with HIV reporter viruses and latently infected clones have been selected that
      reactive HIV in response to inflammatory signals. The cell lines we have
      developed and rigorously characterized will provide an invaluable resource for
      the study of HIV infection in microglial cells as well as studies of microglial
      cell function.

PMID- 27873224
TI  - Therapeutic Potential of Transdermal Glyceryl Trinitrate in the Management of
      Acute Stroke.
AB  - The nitric oxide donor, glyceryl trinitrate (GTN), is a candidate treatment for
      the management of acute stroke with haemodynamic and potential reperfusion and
      neuroprotective effects. When administered as a transdermal patch during the
      acute and subacute phases after stroke, GTN was safe, lowered blood pressure,
      maintained cerebral blood flow, and did not induce cerebral steal or alter
      functional outcome. However, when given within 6 h of stroke onset, GTN reduced
      death and dependency (odds ratio 0.52; 95% confidence interval 0.34-0.78), death,
      disability, cognitive impairment and mood disturbance, and improved quality of
      life (data from two trials, n = 312). In a pooled analysis of four studies (n =
      186), GTN reduced between-visit systolic blood pressure variability over days 1-7
      compared with no GTN (mean difference -2.09; 95% confidence interval -3.83 to 
      0.35; p = 0.019). The efficacy of GTN given in the ultra-acute/pre-hospital
      setting is currently being assessed and, if found to be beneficial, the
      implications for hyperacute stroke practice are significant. Here, we discuss the
      evidence to date, potential mechanisms of action and future possibilities,
      including unanswered questions, for the therapeutic potential of GTN in acute
      stroke.

PMID- 27873227
TI  - The Relationship Between Aortic Root Size and Hypertension: An Unsolved
      Conundrum.
AB  - Thoracic aortic aneurysms rupture and dissection are among the most devastating
      vascular diseases, being characterized by elevated mortality, despite
      improvements in diagnostic imaging and surgical techniques.An increased aortic
      root diameter (ARD) represents the main risk factor for thoracic aortic
      dissection and rupture and for aortic valve regurgitation.Even though arterial
      hypertension is commonly regarded as a predisposing condition for the development
      of thoracic aorta aneurysms, the role of blood pressure (BP) as determinant of
      aortic root enlargement is still controversial. The use of different methods for
      indexation of ARD may have in part contributed to the heterogeneous findings
      obtained in the investigations exploring the relationships between ARD and BP.
      Indeed, the best methods for ARD indexation, as well as the normal values of
      aortic root size, are still a matter of debate.Several non-hemodynamic factors
      influence ARD, including age, gender, and anthropometric variables, such as
      height, weight and their derivatives body surface area (BSA) and body mass index.
      Of these factors, anthropometric variables have the greatest impact.Several
      studies documented an association between ARD enlargement, assessed by
      echocardiography, and some indices of hypertensive target organ damage such as
      left ventricular hypertrophy, diastolic dysfunction, and carotid intima-media
      thickening. Recently, we found that ARD, expressed either as absolute values or
      normalized for BSA (ARD/BSA) or height (ARD/H), was significantly greater in
      hypertensive subjects with chronic kidney disease (CKD) when compared to their
      counterparts with normal renal function. Moreover, at univariate analyses
      estimated glomerular filtration rate (eGFR) showed significant inverse
      correlations with ARD not indexed and with ARD/BSA and ARD/H. Taking into account
      the effect of age, sex, duration of hypertension and other potentially
      confounding factors, in multiple regression analyses, only the association of GFR
      with ARD/H and that between GFR and ARD/BSA remained statistically significant.
      The receiver-operating characteristic curve analysis revealed that an estimated
      GFR of about 50 ml/min/1.73 m2 represents the better threshold to distinguish
      hypertensive patients with dilated aortic root from those with a normal one.Some
      population-based studies showed that an enlarged ARD might predict an adverse
      prognosis, even in absence of aneurysmatic alterations.In the Cardiovascular
      Health Study, a dilated aortic root was independently associated with an
      increased risk for stroke, cardiovascular and total mortality in both sexes and
      with incident congestive heart failure only in men. The relationship between ARD
      and heart failure has been observed also in the Framingham Heart Study. More
      recently, the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study
      demonstrated an independent relationship of ARD/H with incident cardiovascular
      morbidity and mortality.Although the relationship between BP and aortic root size
      is still a matter of debate, increasing evidence seems to support the notion that
      aortic root dilatation, even in absence of aneurysmatic alterations, may be
      regarded as an hypertensive organ damage paralleling other preclinical markers
      whose unfavourable prognostic significance is firmly established. Future studies
      are needed to assess whether or not antihypertensive therapy is able to reduce
      aortic root dimension and the increased risk associated with its enlargement.

PMID- 27873226
TI  - Is Dimension Order Important when Valuing Health States Using Discrete Choice
      Experiments Including Duration?
AB  - BACKGROUND: Discrete choice experiments with duration (DCETTO) can be used to
      estimate utility values for preference-based measures, such as the EQ-5D-5L. For
      self-completion, the health dimensions are presented in a standard order.
      However, for valuation, this may result in order effects. Thus, it is important
      to understand whether health state dimension ordering affects values. The aim of
      this study was to examine the importance of dimension ordering on DCE values
      using EQ-5D-5L. METHODS: A choice experiment presenting two health profiles and a
      third immediate death option was developed. A three-arm study was used, with the
      same 120 choice sets presented online across each arm (n = 360 per arm). Arm 1
      presented the standard EQ-5D-5L dimension order, arm 2 randomised order between
      respondents, and arm 3 randomised within respondents. Conditional logit
      regression was used to assess model consistency, and scale parameter testing was
      used to assess model poolability. RESULTS: There were minor inconsistencies
      across each arm, but the magnitudes of the coefficients produced were generally
      consistent. Arm 3 produced the largest range of utility values (1 to -0.980).
      Scale parameter testing suggested that the models did not differ, and the data
      could be pooled. Follow-up questions did not suggest variation in terms of
      difficulty. CONCLUSIONS: The results suggest that the level of randomisation used
      in DCE health state valuation studies does not significantly impact values, and
      dimension order may not be as important as other study design issues. The results
      support past valuation studies that use the standard order of dimensions.

PMID- 27873225
TI  - How Consistent is the Relationship between Improved Glucose Control and Modelled
      Health Outcomes for People with Type 2 Diabetes Mellitus? a Systematic Review.
AB  - BACKGROUND: There are an increasing number of studies using simulation models to
      conduct cost-effectiveness analyses for type 2 diabetes mellitus. OBJECTIVE: To
      evaluate the relationship between improvements in glycosylated haemoglobin
      (HbA1c) and simulated health outcomes in type 2 diabetes cost-effectiveness
      studies. METHODS: A systematic review was conducted on MEDLINE and EMBASE to
      collect cost-effectiveness studies using type 2 diabetes simulation models that
      reported modelled health outcomes of blood glucose-related interventions in terms
      of quality-adjusted life-years (QALYs) or life expectancy (LE). The data
      extracted included information used to characterise the study cohort, the
      intervention's treatment effects on risk factors and model outcomes. Linear
      regressions were used to test the relationship between the difference in HbA1c
      (?HbA1c) and incremental QALYs (?QALYs) or LE (?LE) of intervention and control
      groups. The ratio between the ?QALYs and ?LE was calculated and a scatterplot
      between the ratio and ?HbA1c was used to explore the relationship between these
      two. RESULTS: Seventy-six studies were included in this research, contributing to
      124 pair of comparators. The pooled regressions indicated that the marginal
      effect of a 1% HbA1c decrease in intervention resulted in an increase in life
      time QALYs and LE of 0.371 (95% confidence interval 0.286-0.456) and 0.642 (95%
      CI 0.494-0.790), respectively. No evidence of heterogeneity between models was
      found. An inverse exponential relationship was found and fitted between the ratio
      (?QALY/?LE) and ?HbA1c. CONCLUSION: There is a consistent relationship between
      ?HbA1c and ?QALYs or ?LE in cost-effectiveness analyses using type 2 diabetes
      simulation models. This relationship can be used as a diagnostic tool for
      decision makers.

PMID- 27873228
TI  - Hypertension in Chronic Kidney Disease.
AB  - Hypertension, a global public health problem, is currently the leading factor in
      the global burden of disease. It is the major modifiable risk factor for heart
      disease, stroke and kidney failure. Chronic kidney disease (CKD) is both a common
      cause of hypertension and CKD is also a complication of uncontrolled
      hypertension. The interaction between hypertension and CKD is complex and
      increases the risk of adverse cardiovascular and cerebrovascular outcomes. This
      is particularly significant in the setting of resistant hypertension commonly
      seen in patient with CKD. The pathophysiology of CKD associated hypertension is
      multi-factorial with different mechanisms contributing to hypertension. These
      pathogenic mechanisms include sodium dysregulation, increased sympathetic nervous
      system and alterations in renin angiotensin aldosterone system activity.
      Standardized blood pressure (BP) measurement is essential in establishing the
      diagnosis and management of hypertension in CKD. Use of ambulatory blood pressure
      monitoring provides an additional assessment of diurnal variation in BP commonly
      seen in CKD patients. The optimal BP target in the treatment of hypertension in
      general and CKD population remains a matter of debate and controversial despite
      recent guidelines and clinical trial data. Medical therapy of patients with CKD
      associated hypertension can be difficult and challenging. Additional evaluation
      by a hypertension specialist may be required in the setting of treatment
      resistant hypertension by excluding pseudo-resistance and treatable secondary
      causes. Treatment with a combination of antihypertensive drugs, including
      appropriate diuretic choice, based on estimated glomerular filtration rate, is a
      key component of hypertension management in CKD patients. In addition to drug
      treatment non-pharmacological approaches including life style modification, most
      important of which is dietary salt restriction, should be included in the
      management of hypertension in CKD patients.

PMID- 27873229
TI  - Subclinical Kidney Damage in Hypertensive Patients: A Renal Window Opened on the
      Cardiovascular System. Focus on Microalbuminuria.
AB  - The kidney is one of the major target organs of hypertension.Kidney damage
      represents a frequent event in the course of hypertension and arterial
      hypertension is one of the leading causes of end-stage renal disease (ESRD).ESRD
      has long been recognized as a strong predictor of cardiovascular (CV) morbidity
      and mortality. However, over the past 20 years a large and consistent body of
      evidence has been produced suggesting that CV risk progressively increases as the
      estimated glomerular filtration rate (eGFR) declines and is already significantly
      elevated even in the earliest stages of renal damage. Data was supported by the
      very large collaborative meta-analysis of the Chronic Kidney Disease Prognosis
      Consortium, which provided undisputable evidence that there is an inverse
      association between eGFR and CV risk. It is important to remember that in
      evaluating CV disease using renal parameters, GFR should be assessed
      simultaneously with albuminuria.Indeed, data from the same meta-analysis indicate
      that also increased urinary albumin levels or proteinuria carry an increased risk
      of all-cause and CV mortality. Thus, lower eGFR and higher urinary albumin values
      are not only predictors of progressive kidney failure, but also of all-cause and
      CV mortality, independent of each other and of traditional CV risk
      factors.Although subjects with ESRD are at the highest risk of CV diseases, there
      will likely be more events in subjects with mil-to-moderate renal dysfunction,
      because of its much higher prevalence.These findings are even more noteworthy
      when one considers that a mild reduction in renal function is very common in
      hypertensive patients.The current European Society of Hypertension (ESH)/European
      Society of Cardiology (ESC) guidelines for the management of arterial
      hypertension recommend to sought in every patient signs of subclinical (or
      asymptomatic) renal damage. This was defined by the detection of eGFR between 30
      mL/min/1.73 m2 and 60 mL/min/1.73 m2 or the presence of microalbuminuria (MAU),
      that is an amount of albumin in the urine of 30-300 mg/day or an
      albumin/creatinine ratio, preferentially on morning spot urine, of 30-300
      mg/g.There is clear evidence that urinary albumin excretion levels, even below
      the cut-off values used to define MAU, are associated with an increased risk of
      CV events. The relationships of MAU with a variety of risk factors, such as blood
      pressure, diabetes and metabolic syndrome and with several indices of subclinical
      organ damage, may contribute, at least in part, to explain the enhanced CV risk
      conferred by MAU. Nonetheless, several studies showed that the association
      between MAU and CV disease remains when all these risk factors are taken into
      account in multivariate analyses. Therefore, the exact pathophysiological
      mechanisms explaining the association between MAU and CV risk remain to be
      elucidated. The simple search for MAU and in general of subclinical renal
      involvement in hypertensive patients may enable the clinician to better assess
      absolute CV risk, and its identification may induce physicians to encourage
      patients to make healthy lifestyle changes and perhaps would prompt to more
      aggressive modification of standard CV risk factors.

PMID- 27873230
TI  - Hypertension in the Hemodialysis Patient.
AB  - Hypertension is common yet difficult to manage in the hemodialysis patients
      population. This chapter discusses various aspects of this problem including its
      prevalence, distinctive pathophysiology, methods of diagnosis and pharmacological
      and non pharmacological treatment approaches. The topic is relevant to any health
      care provider taking care of hemodialysis patients.

PMID- 27873231
TI  - Atherosclerotic Renal Artery Stenosis.
AB  - Atherosclerotic Renal Artery Stenosis is a form or peripheral arterial disease
      that tends to affect older subjects with hyperlipidemia, history of tobacco use,
      and who have other coexistent forms of vascular insufficiency. An abdominal bruit
      on physical exam can be a helpful clue. Slowly progressive, it can lead to
      critical narrowing of the renal arteries which creates a cascade of events such
      as renin-angiotensin-aldosterone activation (RAAS), hypertension, acute pulmonary
      edema, and renal fibrosis. The hypertension is considered a secondary form and
      can even be resistant to multiple antihypertensives. The diagnosis can be made
      with imaging (duplex ultrasound CT scans, MRA, or angiography). Because of the
      unique circulation to the kidney, stenting and angioplasty are rarely curative.
      This was confirmed in three recent large clinical trials. Therapy consists of
      lipid and blood pressure control, and dual anti-platelet agents. Because the
      disease activates the RAAS system, ace inhibitors and angiotensin receptor
      blockers can be useful agents but carry the risk of ischemic nephropathy, a form
      of acute kidney injury related to reduced renal blood flow after challenge with
      these agents. As such these agents are used with caution. Little is known about
      optimal blood pressure agents or the effect of lifestyle modification.

PMID- 27873232
TI  - Evidence-Based Revised View of the Pathophysiology of Preeclampsia.
AB  - Preeclampsia is a life-threatening vascular disorder of pregnancy due to a
      failing stressed placenta. Millions of women risk death to give birth each year
      and globally each year, almost 300,000 lose their life in this process and over
      500,000 babies die as a consequence of preeclampsia. Despite decades of research,
      we lack pharmacological agents to treat it. Maternal endothelial oxidative stress
      is a central phenomenon responsible for the preeclampsia phenotype of high
      maternal blood pressure and proteinuria. In 1997, it was proposed that
      preeclampsia arises due to the loss of VEGF activity, possibly due to elevation
      in anti-angiogenic factor, soluble Flt-1 (sFlt-1). Researchers showed that high
      sFlt-1 and soluble endoglin (sEng) elicit the severe preeclampsia phenotype in
      pregnant rodents. We demonstrated that heme oxygenase-1 (HO-1)/carbon monoxide
      (CO) pathway prevents placental stress and suppresses sFlt-1 and sEng release.
      Likewise, hydrogen sulphide (H2S)/cystathionine-gamma-lyase (Cth) systems limit
      sFlt-1 and sEng and protect against the preeclampsia phenotype in mice.
      Importantly, H2S restores placental vasculature, and in doing so improves lagging
      fetal growth. These molecules act as the inhibitor systems in pregnancy and when
      they fail, preeclampsia is triggered. In this review, we discuss what are the
      hypotheses and models for the pathophysiology of preeclampsia on the basis of
      Bradford Hill causation criteria for disease causation and how further in vivo
      experimentation is needed to establish 'proof of principle'. Hypotheses that fail
      to meet the Bradford Hill causation criteria include abnormal spiral artery
      remodelling and inflammation and should be considered associated or consequential
      to the disorder. In contrast, the protection against cellular stress hypothesis
      that states that the protective pathways mitigate cellular stress by limiting
      elevation of anti-angiogenic factors or oxidative stress and the subsequent
      clinical signs of preeclampsia appear to fulfil most of Bradford Hill causation
      criteria. Identifying the candidates on the roadmap to this pathway is essential
      in developing diagnostics and therapeutics to target the pathogenesis of
      preeclampsia.

PMID- 27873233
TI  - FOUR Score Predicts Early Outcome in Patients After Traumatic Brain Injury.
AB  - BACKGROUND: The aim of the study was to determine whether the Full Outline of
      UnResponsiveness (FOUR) score, which includes eyes opening (E), motor function
      (M), brainstem reflex (B), and respiratory pattern (R), can be used as an
      alternate method to the Glasgow Coma Scale (GCS) in predicting intensive care
      unit (ICU) mortality in traumatic brain injury (TBI) patients. METHODS: From
      January 2015 to June 2015, patients with isolated TBI admitted to the ICU were
      enrolled. Three advanced practice nurses administered the FOUR score, GCS, Acute
      Physiology and Chronic Health Evaluation II (APACHE II), and Therapeutic
      Intervention Scoring System (TISS) concurrently from ICU admissions. The endpoint
      of observation was mortality when the patients left the ICU. Data are presented
      as frequency with percentages, mean with standard deviation, or median with
      interquartile range. Each measurement tool used area under the receiver operating
      characteristic curve to compare the predictive power between these four tools. In
      addition, the difference between survival and death was estimated using the
      Wilcoxon rank sum test. RESULTS: From 55 TBI patients, males (72.73 %) were
      represented more than females, the mean age was 63.1 +/- 17.9, and 19 of 55
      observations (35 %) had a maximum FOUR score of 16. The overall mortality rate
      was 14.6 %. The area under the receiver operating characteristic curve was 74.47
      % for the FOUR score, 74.73 % for the GCS, 81.78 % for the APACHE II, and 53.32 %
      for the TISS. The FOUR score has similar predictive power of mortality compared
      to the GCS and APACHE II. Each of the parameters-E, M, B, and R-of the FOUR score
      showed a significant difference between mortality and survival group, while the
      verbal and eye-opening components of the GCS did not. CONCLUSION: Having similar
      predictive power of mortality compared to the GCS and APACHE II, the FOUR score
      can be used as an alternative in the prediction of early mortality in TBI
      patients in the ICU.

PMID- 27873234
TI  - EEG Monitoring and Antiepileptic Drugs in Children with Severe TBI.
AB  - BACKGROUND: Traumatic brain injury (TBI) causes substantial morbidity and
      mortality in US children. Post-traumatic seizures (PTS) occur in 11-42% of
      children with severe TBI and are associated with unfavorable outcome.
      Electroencephalographic (EEG) monitoring may be used to detect PTS and
      antiepileptic drugs (AEDs) may be used to treat PTS, but national rates of EEG
      and AED use are not known. The purpose of this study was to describe the
      frequency and timing of EEG and AED use in children hospitalized after severe
      TBI. METHODS: Retrospective cohort study of 2165 children at 30 hospitals in a
      probabilistically linked dataset from the National Trauma Data Bank (NTDB) and
      the Pediatric Health Information Systems (PHIS) database, 2007-2010. We included
      children (age <18 years old at admission) with linked NTDB and PHIS records,
      severe (Emergency Department [ED] Glasgow Coma Scale [GCS] <8) TBI, hospital
      length of stay >24 h, and non-missing disposition. The primary outcomes were EEG
      and AED use. RESULTS: Overall, 31.8% of the cohort had EEG monitoring. Of those,
      21.8% were monitored on the first hospital day. The median duration of EEG
      monitoring was 2.0 (IQR 1.0, 4.0) days. AEDs were prescribed to 52.0% of the
      cohort, of whom 61.8% received an AED on the first hospital day. The median
      duration of AED use was 8.0 (IQR 4.0, 17.0) days. EEG monitoring and AED use were
      more frequent in children with known risk factors for PTS. EEG monitoring and AED
      use were not related to hospital TBI volume. CONCLUSION: EEG use is relatively
      uncommon in children with severe TBI, but AEDs are frequently prescribed. EEG
      monitoring and AED use are more common in children with known risk factors for
      PTS.

PMID- 27873236
TI  - Association of Performance Status and Pain in Metastatic Bone Pain Management in
      the Spanish Clinical Setting.
AB  - INTRODUCTION: Bone metastasis is the most common cause of cancer-related pain,
      and metastatic bone pain (MBP) is not only severe but also progressive in many
      patients. The aim of this study was to investigate the association between pain
      management and performance status in patients with metastatic bone cancer in the
      Spanish clinical setting. METHODS: A 3-month follow-up prospective,
      epidemiologic, multicenter study was conducted in 579 patients to assess the
      evolution of their performance, the impact of pain control on sleep and
      functionality, and the degree of pain control according to analgesic treatment.
      RESULTS: In patients with MBP, Eastern Cooperative Oncology Group (ECOG) status
      (1.5 +/- 0.7-1.3 +/- 0.7 and 1.3 +/- 0.8; p < 0.001) and pain (6.5 +/- 1.4-2.8 +/
      1.9 and 2.1 +/- 1.9; p < 0.001) improved significantly from baseline to months 1
      and 3, as did functionality and sleep, after a treatment change consisting of
      increasing the administration of opioids. Evolution of ECOG and pain were closely
      related. ECOG and pain outcomes were significantly more favorable in patients
      treated with opioids versus non-opioid treatment, and in patients who did not
      need rescue medication versus those who did. CONCLUSIONS: MBP is currently poorly
      managed in Spain. ECOG improvement is closely and directly related to pain
      management in MBP. Opioid treatment and a lack of requirements for rescue
      medication are associated with better ECOG and pain outcomes in MBP patients.
      FUNDING: Mundipharma Pharmaceuticals S.L.

PMID- 27873237
TI  - Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative
      Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with
      Blinatumomab Using Historical Data.
AB  - INTRODUCTION: Blinatumomab is a bispecific T cell-engaging antibody construct
      indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor
      acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A
      phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh
      within two cycles and approximately 20% of patients receiving blinatumomab were
      still alive after 2 years. METHODS: The objective of the current analysis was to
      estimate long-term survival of patients receiving blinatumomab beyond the
      observed time period in the clinical study using a large historical observational
      dataset. Conditional survival probabilities of blinatumomab-treated patients
      beyond month 60 were assumed to be the same as the US general population.
      RESULTS: At month 60, the estimated proportion of blinatumomab-treated patients
      alive was more than double that of historical patients (12.6% vs 5.4%). The mean
      overall survival was 76.1 months for blinatumomab patients and 39.8 months for
      historical patients. Sensitivity analyses including additional follow-up data
      from the clinical study showed consistent results. CONCLUSIONS: These findings
      suggest that blinatumomab provides substantial overall survival benefit to
      patients with (R/R) Ph(-) B-precursor ALL compared with salvage chemotherapy.
      FUNDING: Amgen. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01466179 and
      NCT02003612.

PMID- 27873238
TI  - Cardiovascular Safety of Dipeptidyl-Peptidase IV Inhibitors: A Meta-Analysis of
      Placebo-Controlled Randomized Trials.
AB  - BACKGROUND: Large randomized trials have shown conflicting evidence regarding the
      cardiovascular safety of dipeptidyl-peptidase 4 (DPP-4) inhibitors. Systematic
      reviews have been limited by incomplete data and inclusion of observational
      studies. This study aimed to systematically evaluate the cardiovascular safety of
      DPP-4 inhibitors in patients with type 2 diabetes. METHODS: Electronic databases
      were searched for randomized trials that compared DPP-4 inhibitors versus placebo
      and reported cardiovascular outcomes. The main outcome assessed in this analysis
      was heart failure. Other outcomes included all-cause mortality, cardiovascular
      mortality, myocardial infarction, and ischemic stroke. Summary odds ratios (ORs)
      were primarily constructed using Peto's model. RESULTS: A total of 90 trials with
      66,730 patients were included. Compared with placebo, DPP-4 inhibitors were
      associated with a non-significant increased risk of heart failure [OR 1.11, 95%
      confidence interval (CI) 0.99-1.25, P = 0.07] at a mean of 108 weeks. The risk of
      all-cause mortality (OR 1.03, 95% CI 0.94-1.12, P = 0.53), cardiovascular
      mortality (OR 1.02, 95% CI 0.92-1.14, P = 0.72), myocardial infarction (OR 0.98,
      95% CI 0.88-1.09, P = 0.69), and ischemic stroke (OR 0.99, 95% CI 0.85-1.15, P =
      0.92) was similar between both groups. CONCLUSION: In patients with type 2
      diabetes, the safety profile of DPP-4 inhibitors is similar to placebo. As a
      class, there is only weak evidence for an increased risk of heart failure.

PMID- 27873239
TI  - Effects of acetaminophen on mitochondrial complex I activity in the rat liver and
      kidney: a PET study with 18F-BCPP-BF.
AB  - BACKGROUND: In the present study, 2-tert-butyl-4-chloro-5-[6-(4-18F-fluorobutoxy)
      pyridin-3-ylmethoxy]-2H-pyridazin-3-one (18F-BCPP-BF), a PET probe for
      mitochondrial complex I (MC-I), was used to validate whether MC-I is a useful
      biomarker for detecting acetaminophen-induced dysfunctions in the liver and
      kidney. The kinetic and distribution of 18F-BCPP-BF were assessed in rats using
      high-resolution animal PET in vivo. The binding specificity of 18F-BCPP-BF to MC
      I in the liver and kidney was confirmed by the pre-administration of rotenone, a
      specific MC-I inhibitor. The effects of acetaminophen on MC-I activity were
      assessed 2 and 24 h after the administration of vehicle or acetaminophen at a
      dose of 100 or 300 mg/kg. Biochemical parameters in plasma and urine were
      assessed 2, 6, and 24 h after the administration of vehicle or acetaminophen.
      RESULTS: The uptake of 18F-BCPP-BF by the liver and kidney was significantly
      inhibited by the pre-administration of rotenone. Two and more hours after the
      administration of acetaminophen, the uptake of 18F-BCPP-BF was dose-dependently
      reduced in the liver, even at 100 mg/kg, and in the kidney at 300 mg/kg, whereas
      biological parameters started to be affected 6 h or later at doses of 300 mg/kg.
      CONCLUSIONS: The present study demonstrated that 18F-BCPP-BF has potential as a
      PET probe for the quantitative imaging of hepatic and renal dysfunction as
      impaired MC-I activity in the early phase of the treatment for an overdose of
      acetaminophen in the living body with PET.

PMID- 27873235
TI  - Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain
      Multisetting Multicentric Survey (IOPS-MS).
AB  - INTRODUCTION: An ongoing national multicenter survey [Italian Oncologic Pain
      multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of
      breakthrough cancer pain (BTP) in different clinical settings. Preliminary data
      from the first 1500 cancer patients with BTP enrolled in this study are presented
      here. METHODS: Thirty-two clinical centers are involved in the survey. A
      diagnosis of BTP was performed by a standard algorithm. Epidemiological data,
      Karnofsky index, stage of disease, presence and sites of metastases, ongoing
      oncologic treatment, and characteristics of background pain and BTP and their
      treatments were recorded. Background pain and BTP intensity were measured.
      Patients were also questioned about BTP predictability, BTP onset (<=10 or >10
      min), BTP duration, background and BTP medications and their doses, time to
      meaningful pain relief after BTP medication, and satisfaction with BTP
      medication. The occurrence of adverse reactions was also assessed, as well as
      mucosal toxicity. RESULTS: Background pain was well controlled with opioid
      treatment (numerical rating scale 3.0 +/- 1.1). Patients reported 2.5 +/- 1.6 BTP
      episodes/day with a mean intensity of 7.5 +/- 1.4 and duration of 43 +/- 40 min;
      977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%)
      reported a rapid onset of BTP (<=10 min). Higher patient satisfaction was
      reported by patients treated with fast onset opioids. CONCLUSIONS: These
      preliminary data underline that the standard algorithm used is a valid tool for a
      proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is
      crucial for patients' satisfaction. The final IOPS-MS data are necessary to
      understand relationships between BTP characteristics and other clinical variables
      in oncologic patients. FUNDING: Molteni Farmaceutici, Italy.

PMID- 27873240
TI  - Improved safety and efficacy of 213Bi-DOTATATE-targeted alpha therapy of
      somatostatin receptor-expressing neuroendocrine tumors in mice pre-treated with L
      lysine.
AB  - BACKGROUND: Targeted alpha therapy (TAT) offers advantages over current beta
      emitting conjugates for peptide receptor radionuclide therapy (PRRT) of
      neuroendocrine tumors. PRRT with 177Lu-DOTATATE or 90Y-DOTATOC has shown dose
      limiting nephrotoxicity due to radiopeptide retention in the proximal tubules.
      Pharmacological protection can reduce renal uptake of radiopeptides, e.g.,
      positively charged amino acids, to saturate in the proximal tubules, thereby
      enabling higher radioactivity to be safely administered. The aim of this
      preclinical study was to evaluate the therapeutic effect of 213Bi-DOTATATE with
      and without renal protection using L-lysine in mice. Tumor uptake and kinetics as
      a function of injected mass of peptide (range 0.03-3 nmol) were investigated
      using 111In-DOTATATE. These results allowed estimation of the mean radiation
      absorbed tumor dose for 213Bi-DOTATATE. Pharmacokinetics and dosimetry of 213Bi
      DOTATATE was determined in mice, in combination with renal protection. A dose
      escalation study with 213Bi-DOTATATE was performed to determine the maximum
      tolerated dose (MTD) with and without pre-administration of L-lysine as for renal
      protection. Neutrophil gelatinase-associated lipocalin (NGAL) served as renal
      biomarker to determine kidney injury. RESULTS: The maximum mean radiation
      absorbed tumor dose occurred at 0.03 nmol and the minimum at 3 nmol. Similar mean
      radiation absorbed tumor doses were determined for 0.1 and 0.3 nmol with a mean
      radiation absorbed dose of approximately 0.5 Gy/MBq 213Bi-DOTATATE. The optimal
      mass of injected peptide was found to be 0.3 nmol. Tumor uptake was similar for
      111In-DOTATATE and 213Bi-DOTATATE at 0.3 nmol peptide. Lysine reduced the renal
      uptake of 213Bi-DOTATATE by 50% with no effect on the tumor uptake. The MTD was
      <13.0 +/- 1.6 MBq in absence of L-lysine and 21.7 +/- 1.9 MBq with L-lysine renal
      protection, both imparting an LD50 mean renal radiation absorbed dose of 20 Gy. A
      correlation was found between the amount of injected radioactivity and NGAL
      levels. CONCLUSIONS: The therapeutic potential of 213Bi-DOTATATE was illustrated
      by significantly decreased tumor burden and improved overall survival. Renal
      protection with L-lysine immediately prior to TAT with 213Bi-DOTATATE prolonged
      survival providing substantial evidence for pharmacological nephron blockade to
      mitigate nephrotoxicity.

PMID- 27873243
TI  - Antibiotics: Precious Goods in Changing Times.
AB  - Antibiotics represent a first line of defense of diverse microorganisms, which
      produce and use antibiotics to counteract natural enemies or competitors for
      nutritional resources in their nearby environment. For antimicrobial activity,
      nature has invented a great variety of mechanisms of antibiotic action that
      involve the perturbation of essential bacterial structures or biosynthesis
      pathways of macromolecules such as the bacterial cell wall, DNA, RNA, or
      proteins, thereby threatening the specific microbial lifestyle and eventually
      even survival. However, along with highly inventive modes of antibiotic action,
      nature also developed a comparable set of resistance mechanisms that help the
      bacteria to circumvent antibiotic action. Microorganisms have evolved specific
      adaptive responses that allow appropriately reacting to the presence of
      antimicrobial agents, ensuring survival during antimicrobial stress. In times of
      rapid development and spread of antibiotic (multi-)resistance, we need to explore
      new, resistance-breaking strategies to counteract bacterial infections. This
      chapter intends to give an overview of common antibiotics and their target
      pathways. It will also discuss recent advances in finding new antibiotics with
      novel modes of action, illustrating that nature's repertoire of innovative new
      antimicrobial agents has not been fully exploited yet, and we still might find
      new drugs that help to evade established antimicrobial resistance strategies.

PMID- 27873241
TI  - Predictive factors of 18F-choline PET/CT positivity in patients with prostate
      cancer recurrence after radiation therapy: is the impact of PSA nadir
      underestimated?
AB  - BACKGROUND: The objective of this study is to explore the impact of PSA nadirs on
      detection rates of prostate cancer (PCa) recurrence with 18F-choline (CH) PET/CT
      after external beam radiation therapy (EBRT). METHODS: In this retrospective
      study, data were collected from 54 patients with suspicion of PCa biochemical
      recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage
      therapy in the absence of PSA decrease after initial treatment), who underwent
      18F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected
      from patient files. Relative PSA was calculated by subtracting the nadir from the
      trigger PSA. RESULTS: Median PSA nadir was 0.31 (0.01-13.31) ng/mL, trigger PSA
      was 7.85 (0.47-111.60) ng/mL, and relative PSA was 6.05 (0.24-104.59) ng/mL.
      Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or
      regional in 29 patients, distant in 15 and combined both in four, with no
      association between PSA values and sites of recurrence. In univariate analysis,
      trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p =
      0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In
      subgroup analysis, these significant differences were only found in the salvage
      EBRT group. Akaike Information Criterion multivariate model comparison found that
      relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt).
      18F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4
      patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2<=
      PSAt <=4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50%
      (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into
      account instead of trigger PSA, with seven (13%) patients changing subgroups.
      CONCLUSIONS: We found a high overall detection rate and an increase in detection
      rates proportional to trigger and relative PSAs. Although relative PSA, taking
      into account PSA nadir, was a better predictive factor of PET/CT positivity in
      univariate analysis, this was most noticeable for high PSAs. For low PSAs,
      trigger PSA remains most relevant. Larger series with intermediate PSA values
      need to be studied to fully apprehend nadir impact.

PMID- 27873242
TI  - Effect of Repeated Whole Blood Donations on Aerobic Capacity and Hemoglobin Mass
      in Moderately Trained Male Subjects: A Randomized Controlled Trial.
AB  - BACKGROUND: The aims of the present study were to investigate the impact of three
      whole blood donations on endurance capacity and hematological parameters and to
      determine the duration to fully recover initial endurance capacity and
      hematological parameters after each donation. METHODS: Twenty-four moderately
      trained subjects were randomly divided in a donation (n = 16) and a placebo (n =
      8) group. Each of the three donations was interspersed by 3 months, and the
      recovery of endurance capacity and hematological parameters was monitored up to 1
      month after donation. RESULTS: Maximal power output, peak oxygen consumption, and
      hemoglobin mass decreased (p < 0.001) up to 4 weeks after a single blood donation
      with a maximal decrease of 4, 10, and 7%, respectively. Hematocrit, hemoglobin
      concentration, ferritin, and red blood cell count (RBC), all key hematological
      parameters for oxygen transport, were lowered by a single donation (p < 0.001)
      and cumulatively further affected by the repetition of the donations (p < 0.001).
      The maximal decrease after a blood donation was 11% for hematocrit, 10% for
      hemoglobin concentration, 50% for ferritin, and 12% for RBC (p < 0.001). Maximal
      power output cumulatively increased in the placebo group as the maximal exercise
      tests were repeated (p < 0.001), which indicates positive training adaptations.
      This increase in maximal power output over the whole duration of the study was
      not observed in the donation group. CONCLUSIONS: Maximal, but not submaximal,
      endurance capacity was altered after blood donation in moderately trained people
      and the expected increase in capacity after multiple maximal exercise tests was
      not present when repeating whole blood donations.

PMID- 27873244
TI  - Mining Bacterial Genomes for Secondary Metabolite Gene Clusters.
AB  - With the emergence of bacterial resistance against frequently used antibiotics,
      novel antibacterial compounds are urgently needed. Traditional bioactivity-guided
      drug discovery strategies involve laborious screening efforts and display high
      rediscovery rates. With the progress in next generation sequencing methods and
      the knowledge that the majority of antibiotics in clinical use are produced as
      secondary metabolites by bacteria, mining bacterial genomes for secondary
      metabolites with antimicrobial activity is a promising approach, which can guide
      a more time and cost-effective identification of novel compounds. However, what
      sounds easy to accomplish, comes with several challenges. To date, several tools
      for the prediction of secondary metabolite gene clusters are available, some of
      which are based on the detection of signature genes, while others are searching
      for specific patterns in gene content or regulation.Apart from the mere
      identification of gene clusters, several other factors such as determining
      cluster boundaries and assessing the novelty of the detected cluster are
      important. For this purpose, comparison of the predicted secondary metabolite
      genes with different cluster and compound databases is necessary. Furthermore, it
      is advisable to classify detected clusters into gene cluster families. So far,
      there is no standardized procedure for genome mining; however, different
      approaches to overcome all of these challenges exist and are addressed in this
      chapter. We give practical guidance on the workflow for secondary metabolite gene
      cluster identification, which includes the determination of gene cluster
      boundaries, addresses problems occurring with the use of draft genomes, and gives
      an outlook on the different methods for gene cluster classification. Based on
      comprehensible examples a protocol is set, which should enable the readers to
      mine their own genome data for interesting secondary metabolites.

PMID- 27873245
TI  - Production of Antimicrobial Compounds by Fermentation.
AB  - The production of biologically active metabolites, e.g., antimicrobial compounds,
      is an essential step in the discovery and development process of medicinal drugs
      based on natural products. To get a hand on the compound of interest it first has
      to be biosynthesized by the corresponding producer, mostly a microorganism. In
      this chapter, a general workflow, which can easily be adapted to the lab, is
      described. Both fermentation on solid and in liquid medium is explained, and
      examples of hand on procedures are given.

PMID- 27873246
TI  - Structure Elucidation of Antibiotics by Nmr Spectroscopy.
AB  - Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for the
      structure elucidation of antibiotics in solution. Over the past 30 years there
      have been numerous publications describing the use of NMR to characterize
      naturally derived or synthetic antibiotics. A large number of one-dimensional
      (1D) and two-dimensional (2D) NMR methods are available today and the list
      continues to expand. In this chapter, we will consider the key NMR experiments
      that provide useful information for compound structure elucidation.

PMID- 27873248
TI  - Cytotoxicity Assays as Predictors of the Safety and Efficacy of Antimicrobial
      Agents.
AB  - The development of safe antimicrobial agents is important for the effective
      treatment of pathogens. From a multitude of discovered inhibitory compounds only
      few antimicrobial agents are able to enter the market. Many antimicrobials are,
      on the one hand, quite effective in killing pathogens but, on the other hand,
      cytotoxic to eukaryotic cells. Cell health can be monitored by various methods.
      Plasma membrane integrity, DNA synthesis, enzyme activity, and reducing
      conditions within the cell are known indicators of cell viability and cell death.
      For a comprehensive overview, methods to analyze cytotoxic and hemolytic effects,
      e.g., lactate dehydrogenase release, cell proliferation analysis, cell viability
      analysis, and hemolysis assay of antimicrobial compounds on human cells, are
      described in this chapter.

PMID- 27873247
TI  - Computer-Aided Drug Design Methods.
AB  - Computational approaches are useful tools to interpret and guide experiments to
      expedite the antibiotic drug design process. Structure-based drug design (SBDD)
      and ligand-based drug design (LBDD) are the two general types of computer-aided
      drug design (CADD) approaches in existence. SBDD methods analyze macromolecular
      target 3-dimensional structural information, typically of proteins or RNA, to
      identify key sites and interactions that are important for their respective
      biological functions. Such information can then be utilized to design antibiotic
      drugs that can compete with essential interactions involving the target and thus
      interrupt the biological pathways essential for survival of the microorganism(s).
      LBDD methods focus on known antibiotic ligands for a target to establish a
      relationship between their physiochemical properties and antibiotic activities,
      referred to as a structure-activity relationship (SAR), information that can be
      used for optimization of known drugs or guide the design of new drugs with
      improved activity. In this chapter, standard CADD protocols for both SBDD and
      LBDD will be presented with a special focus on methodologies and targets
      routinely studied in our laboratory for antibiotic drug discoveries.

PMID- 27873250
TI  - Determination of Bacterial Membrane Impairment by Antimicrobial Agents.
AB  - The bacterial cytoplasmic membrane separates the cell from its environment and
      acts as a selective permeability barrier. In addition, it functions in energy
      conservation, transport, and biosynthesis processes. Antimicrobial agents
      disrupting these functions may lead to pleiotropic effects, including leakage of
      low molecular weight compounds such as ions, amino acids and ATP, and subsequent
      membrane depolarization. This article describes two techniques to assess
      antibiotic-induced membrane impairment in vivo.

PMID- 27873249
TI  - Application of a Bacillus subtilis Whole-Cell Biosensor (PliaI-lux) for the
      Identification of Cell Wall Active Antibacterial Compounds.
AB  - Whole-cell biosensors, based on the visualization of a reporter strain's response
      to a particular stimulus, are a robust and cost-effective means to monitor
      defined environmental conditions or the presence of chemical compounds. One
      specific field in which such biosensors are frequently applied is drug discovery,
      i.e., the screening of large numbers of bacterial or fungal strains for the
      production of antimicrobial compounds. We here describe the application of a
      luminescence-based Bacillus subtilis biosensor for the discovery of cell wall
      active substances. The system is based on the well-characterized promoter P liaI
      , which is induced in response to a wide range of conditions that cause cell
      envelope stress, particularly antibiotics that interfere with the membrane
      anchored steps of cell wall biosynthesis. A simple "spot-on-lawn" assay, where
      colonies of potential producer strains are grown directly on a lawn of the
      reporter strain, allows for quantitative and time-resolved detection of
      antimicrobial compounds. Due to the very low technical demands of this procedure,
      we expect it to be easily applicable to a large variety of candidate producer
      strains and growth conditions.

PMID- 27873251
TI  - Mass-Sensitive Biosensor Systems to Determine the Membrane Interaction of
      Analytes.
AB  - Biosensors are devices that transform a biological interaction into a readout
      signal, which is evaluable for analytical purposes. The general strength of
      biosensor approaches is the avoidance of time-consuming and cost-intensive
      labeling procedures of the analytes. In this chapter, we give insight into a mass
      sensitive surface-acoustic wave (SAW) biosensor, which represents an elegant and
      highly sensitive method to investigate binding events at a molecular level. The
      principle of SAW technology is based on the piezoelectric properties of the
      sensors, so as to binding events and their accompanied mass increase at the
      sensor surface are detectable by a change in the oscillation of the surface
      acoustic wave. In combination with model membranes, transferred to the sensor
      surface, the analytical value of SAW biosensors has strongly been increased and
      extended to different topics of biomedical investigations, including antibiotic
      research. The interaction with the bacterial membrane or certain target
      structures therein is the essential mode of action for various antibacterial
      compounds. Beside targeted interaction, an unspecific membrane binding or
      membrane insertion of drugs can contribute to the antibacterial activity by
      changing the lateral order of membrane constituents or by interfering with the
      membrane barrier function. Those pleiotropic effects are hardly to illustrate in
      the bacterial systems and need a detailed view at the in vitro level. Here, we
      illustrate the usefulness of a SAW biosensor in combination with model membranes
      to investigate the mode of membrane interaction of antibiotic active peptides.
      Using two different peptides we exemplary describe the interaction analysis in a
      two-step gain of information: (1) a binding intensity or affinity by analyzing
      the phase changes of oscillation, and (2) mode of membrane interaction, i.e.,
      surface binding or internalization of the peptide by following the amplitude of
      oscillation.

PMID- 27873252
TI  - Measurement of Cell Membrane Fluidity by Laurdan GP: Fluorescence Spectroscopy
      and Microscopy.
AB  - Membrane fluidity is a critical parameter of cellular membranes which cells
      continuously strive to maintain within a viable range. An interference with the
      correct membrane fluidity state can strongly inhibit cell function. Triggered
      changes in membrane fluidity have been postulated to contribute to the mechanism
      of action of membrane targeting antimicrobials, but the corresponding analyses
      have been hampered by the absence of readily available analytical tools. Here, we
      provide detailed protocols that allow straightforward measurement of antibiotic
      compound-triggered changes in membrane fluidity both in vivo and in vitro.

PMID- 27873253
TI  - In Vitro Assays to Identify Antibiotics Targeting DNA Metabolism.
AB  - DNA metabolism embodies a number of biochemical pathways, which include targets
      of clinically used antibiotics as well as those that are only being explored as
      potential targets for inhibitory compounds. We give an overview of representative
      cell-based and enzymatic assays suitable for high-throughput-driven search for
      novel DNA metabolism inhibitors of established and novel DNA metabolism targets
      in bacteria. The protocol for a colorimetric coupled primase-inorganic
      pyrophosphatase assay developed by our group is described in detail.

PMID- 27873255
TI  - Reporter Gene-Based Screening for TPP Riboswitch Activators.
AB  - With the rise of multidrug resistant bacteria and a growing number of nosocomial
      infections, there has been an increased interest in finding new antibacterial
      drugs and drug targets. Riboswitches represent attractive new antibacterial drug
      targets, because they not only inherently recognize a specific metabolite or ion
      with their RNA aptamer domain, but also often regulate essential metabolic
      pathways. Here, we describe a reporter gene-based screen to identify compounds
      that activate the thiamine pyrophosphate (TPP) riboswitch in bacteria. This assay
      can be easily adapted for different riboswitch classes and thus has the potential
      to target many essential metabolic pathways and a broad spectrum of bacterial
      pathogens.

PMID- 27873254
TI  - Fluorescence-Based Real-Time Activity Assays to Identify RNase P Inhibitors.
AB  - Transfer RNA is transcribed as precursor molecules that are processed before
      participating in translation catalyzed by the ribosome. Ribonuclease P is the
      endonuclease that catalyzes the 5' end maturation of precursor tRNA and it is
      essential for cell survival. Bacterial RNase P has a distinct subunit composition
      compared to the eukaryal counterparts; therefore, it is an attractive
      antibacterial target. Here, we describe a real-time fluorescence-based RNase P
      activity assay using fluorescence polarization/anisotropy with a 5' end
      fluorescein-labeled pre-tRNAAsp substrate. This FP/FA assay is sensitive, robust,
      and easy to transition to a high-throughput mode and it also detects ligands that
      interact with pre-tRNA. We apply this FP/FA assay to measure Bacillus subtilis
      RNase P activity under single and multiple turnover conditions in a continuous
      format and a high-throughput screen of inhibitors, as well as determining the
      dissociation constant of pre-tRNA for small molecules.

PMID- 27873256
TI  - Cell-Based Fluorescent Screen to Identify Inhibitors of Bacterial Translation
      Initiation.
AB  - A strategy that can be applied to the research of new molecules with
      antibacterial activity is to look for inhibitors of essential bacterial processes
      within large collections of chemically heterogeneous compounds. The
      implementation of this approach requires the development of proper assays aimed
      at the identification of molecules interfering with specific cell pathways and
      potentially applicable to the high throughput analysis of large chemical library.
      Here, I describe a fluorescence-based whole-cell assay in Escherichia coli
      devised to find inhibitors of the translation initiation pathway. Translation is
      a complex and essential mechanism. It involves numerous sub-steps performed by
      factors that are in many cases sufficiently dissimilar in bacterial and
      eukaryotic cells to be targetable with domain-specific drugs. As a matter of
      fact, translation has been proven as one of the few bacterial mechanisms
      pharmacologically tractable with specific antibiotics. The assay described in
      this chapter is tailored to the identification of molecules affecting the first
      stage of translation initiation, which is the most dissimilar step in bacteria
      vs. mammals. The effect of the compounds under analysis is assayed in living
      cells, thus allowing evaluating their in vivo performance as inhibitors of
      translation initiation. Compared with other assays for antibacterials, the major
      advantages of this screen are its simplicity and high mechanism specificity.

PMID- 27873257
TI  - Bacterial Histidine Kinases: Overexpression, Purification, and Inhibitor Screen.
AB  - Bacterial histidine kinases are promising targets for new antimicrobial agents.
      In antibacterial therapy such agents could inhibit bacterial growth by targeting
      essential two-component regulatory systems or resensitize bacteria to known
      antibiotics by blocking stress responses like the cell wall stress response.
      However, (1) activity assays using the truncated phosphorylation domains have
      been shown to produce artifacts and (2) the purification of the full-length
      histidine kinases is complicated. Here, we describe a standard protocol for the
      recombinant expression and purification of functional full-length histidine
      kinases and other membrane proteins from gram-positive bacteria that do not
      harbor more than two trans-membrane domains using an Escherichia coli host. This
      guide also presents in vitro phosphorylation assays to screen for new
      antimicrobial compounds that target bacterial histidine kinases using
      radioactively labeled ATP and, as a novel approach, Phos-tag acrylamide gel
      electrophoresis to detect phosphorylated proteins by mobility shift in the
      polyacrylamide gel.

PMID- 27873258
TI  - Expression Profiling of Antibiotic-Resistant Bacteria Obtained by Laboratory
      Evolution.
AB  - To elucidate the mechanisms of antibiotic resistance, integrating phenotypic and
      genotypic features in resistant strains is important. Here, we describe the
      expression profiling of antibiotic-resistant Escherichia coli strains obtained by
      laboratory evolution, and a method for extracting a small number of genes whose
      expression changes can contribute to the acquisition of resistance.

PMID- 27873259
TI  - Sample Preparation for Mass-Spectrometry Based Absolute Protein Quantification in
      Antibiotic Stress Research.
AB  - Absolute protein quantification is an essential tool for system biology
      approaches and elucidation of stoichiometry of multi-protein complexes. In this
      chapter, a universal protocol for gel free absolute protein quantification in
      bacterial systems is described, which can be used for sample preparation prior to
      miscellaneous mass-spectrometry-based quantification workflows like AQUA, Hi3,
      and emPAI. In addition, a focus has been set to the specific challenges in
      antibiotic stress research.

PMID- 27873260
TI  - Label-Free Quantitation of Ribosomal Proteins from Bacillus subtilis for
      Antibiotic Research.
AB  - Current research is focusing on ribosome heterogeneity as a response to changing
      environmental conditions and stresses, such as antibiotic stress. Altered
      stoichiometry and composition of ribosomal proteins as well as association of
      additional protein factors are mechanisms for shaping the protein expression
      profile or hibernating ribosomes. Here, we present a method for the isolation of
      ribosomes to analyze antibiotic-induced changes in the composition of ribosomes
      in Bacillus subtilis or other bacteria. Ribosomes and associated proteins are
      isolated by ultracentrifugation and proteins are identified and quantified using
      label-free mass spectrometry.

PMID- 27873261
TI  - Functional Metagenomics to Study Antibiotic Resistance.
AB  - The construction and screening of metagenomic expression libraries has great
      potential to identify novel genes and their functions. Here, we describe
      metagenomic library preparation from fecal DNA, screening of libraries for
      antibiotic resistance genes (ARGs), massively parallel DNA sequencing of the
      enriched DNA fragments, and a computational pipeline for high-throughput assembly
      and annotation of functionally selected DNA.

PMID- 27873262
TI  - Epidemiological Surveillance and Typing Methods to Track Antibiotic Resistant
      Strains Using High Throughput Sequencing.
AB  - High-Throughput Sequencing (HTS) technologies transformed the microbial typing
      and molecular epidemiology field by providing the cost-effective ability for
      researchers to probe draft genomes, not only for epidemiological markers but also
      for antibiotic resistance and virulence determinants. In this chapter, we provide
      protocols for the analysis of HTS data for the determination of multilocus
      sequence typing (MLST) information and for determining presence or absence of
      antibiotic resistance genes.

PMID- 27873264
TI  - Current Trends and Alternative Scenarios in EBV Research.
AB  - Epstein-Barr virus (EBV) infection is associated with several distinct
      hematological and epithelial malignancies, e.g., Burkitt lymphoma, Hodgkin
      lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and others. The
      association with several malignant tumors of local and worldwide distribution
      makes EBV one of the most important tumor viruses. Furthermore, because EBV can
      cause posttransplant lymphoproliferative disease, transplant medicine has to deal
      with EBV as a major pathogenic virus second only to cytomegalovirus. In this
      review, we summarize briefly the natural history of EBV infection and outline
      some of the recent advances in the pathogenesis of the major EBV-associated
      neoplasms. We present alternative scenarios and discuss them in the light of most
      recent experimental data. Emerging research areas including EBV-induced patho
      epigenetic alterations in host cells and the putative role of exosome-mediated
      information transfer in disease development are also within the scope of this
      review. This book contains an in-depth description of a series of modern
      methodologies used in EBV research. In this introductory chapter, we thoroughly
      refer to the applications of these methods and demonstrate how they contributed
      to the understanding of EBV-host cell interactions. The data gathered using
      recent technological advancements in molecular biology and immunology as well as
      the application of sophisticated in vitro and in vivo experimental models
      certainly provided deep and novel insights into the pathogenetic mechanisms of
      EBV infection and EBV-associated tumorigenesis. Furthermore, the development of
      adoptive T cell immunotherapy has provided a novel approach to the therapy of
      viral disease in transplant medicine and hematology.

PMID- 27873265
TI  - Epstein-Barr Virus: Clinical Diagnostics.
AB  - The vast majority of the human adult population is infected with Epstein-Barr
      virus (EBV), and the majority of the EBV-infected individuals tolerates the
      infection well, without any further symptoms after primary infection. In cases of
      individuals which undergo primary infection in the form of an infectious
      mononucleosis, or which have undergone primary infection in their past, it is
      sometimes important to appraise symptomatic disease or differentiate infectious
      mononucleosis from other conditions. In these cases, serological methods, i.e.,
      immunofluorescence, ELISA, or Western blot, are the methods of choice to come to
      an unequivocal diagnostic conclusion, while the detection and quantification of
      viral DNA through PCR plays a minor role.On the other hand, in a minority of the
      human population, EBV infection is associated or causally linked with autoimmune
      or malignant disease. Especially in the bone marrow or solid organ transplanted,
      or in otherwise severely immune-suppressed patients, prolonged EBV primary
      infection or EBV reactivation from latency may be a serious and life-threatening
      complication which needs to be diagnosed the faster the better, in order to take
      therapeutic steps in time. Determining the serostatus correctly is also important
      in these cases. However, the direct and quantitative detection of viral DNA are
      of importance for the diagnosis of serious EBV disease and its monitoring.In the
      following, we give an overview of diagnostic methods to accurately determine EBV
      serostatus and viral load. We evaluate the advantages and disadvantages of each
      method and report on the diagnostic significance of each and how to resolve
      diagnostic problems in case of uncertainties. For practical procedures, we refer
      to the detailed instruction manuals of the respective test kit manufacturers
      which have to be closely followed for reliable results.

PMID- 27873263
TI  - Effects of volume resuscitation on the microcirculation in animal models of
      lipopolysaccharide sepsis: a systematic review.
AB  - BACKGROUND: Recent research has identified an increased rate of mortality
      associated with fluid bolus therapy for severe sepsis and septic shock, but the
      mechanisms are still not well understood. Fluid resuscitation therapy
      administered for sepsis and septic shock targets restoration of the macro
      circulation, but the pathogenesis of sepsis is complex and includes
      microcirculatory dysfunction. OBJECTIVE: The objective of the study is to
      systematically review data comparing the effects of different types of fluid
      resuscitation on the microcirculation in clinically relevant animal models of
      lipopolysaccharide-induced sepsis. METHODS: A structured search of PubMed/MEDLINE
      and EMBASE for relevant publications from 1 January 1990 to 31 December 2015 was
      performed, in accordance with PRISMA guidelines. RESULTS: The number of published
      papers on sepsis and the microcirculation has increased steadily over the last 25
      years. We identified 11 experimental animal studies comparing the effects of
      different fluid resuscitation regimens on the microcirculation. Heterogeneity
      precluded any meta-analysis. CONCLUSIONS: Few animal model studies have been
      published comparing the microcirculatory effects of different types of fluid
      resuscitation for sepsis and septic shock. Biologically relevant animal model
      studies remain necessary to enhance understanding regarding the mechanisms by
      which fluid resuscitation affects the microcirculation and to facilitate the
      transfer of basic science discoveries to clinical applications.

PMID- 27873266
TI  - Establishment of EBV-Infected Lymphoblastoid Cell Lines.
AB  - Lymphoblastoid cell lines (LCLs) can be generated easily by in vitro EBV
      infection of B lymphocytes collected from any individual. In vitro, these EBV
      infected B cell cultures yield proliferating, transformed lines referred to as
      lymphoblastoid cell lines (LCLs).

PMID- 27873267
TI  - Generation and Infection of Organotypic Cultures with Epstein-Barr Virus.
AB  - While numerous model systems are available to study EBV latency in B cells and
      have contributed greatly to our understanding of the role of these cells in the
      viral life cycle, models to study the EBV life cycle in epithelial cells in vitro
      are lacking. Epithelial cells are poorly infected in vitro, and EBV-infected cell
      lines have not been successfully obtained from epithelial tumors. Recently, we
      have demonstrated that organotypic cultures of oral keratinocytes can be used as
      a model to study EBV infection in the epithelial tissue. These "raft" cultures
      generate a stratified tissue resembling the epithelium seen in vivo with a
      proliferating basal layer and differentiating suprabasal layers. Here, we
      describe generation of EBV-infected raft cultures established from primary oral
      mucosal epithelial cells, which exhibit high levels of productive replication
      induced by differentiation, as well as methods to analyze EBV infection.

PMID- 27873268
TI  - Affinity Purification-Mass Spectroscopy Methods for Identifying Epstein-Barr
      Virus-Host Interactions.
AB  - Considerable insight into the function and mechanism of action of viral proteins
      has come from identifying the cellular proteins with which they interact. In
      recent years, mass spectrometry-based methods have emerged as the method of
      choice for protein interaction discovery due to their comprehensive and unbiased
      nature. Methods involving single affinity purifications of epitope-tagged viral
      proteins (AP-MS) and tandem affinity purifications of viral proteins with two
      purification tags (TAP tagging) have both been used to identify novel host
      interactions with EBV proteins. However, to date these methods have only been
      applied to a small number of EBV proteins. Here we provide detailed methods of AP
      MS and TAP tagging approaches that can be applied to any EBV protein in order to
      discover its host interactions.

PMID- 27873269
TI  - The Use of 3D Telomere FISH for the Characterization of the Nuclear Architecture
      in EBV-Positive Hodgkin's Lymphoma.
AB  - The 3D nuclear architecture is closely related to cellular functions and
      chromosomes are organized in distinct territories. Quantitative 3D telomere FISH
      analysis (3D Q-FISH) and 3D super-resolution imaging (3D-SIM) at a resolution up
      to 80 nm as well as the recently developed combined quantitative 3D TRF2-telomere
      immune FISH technique (3D TRF2/Telo-Q-FISH) have substantially contributed to
      elucidate molecular pathogenic mechanisms of hematological diseases. Here we
      report the methods we applied to uncover major molecular steps involved in the
      pathogenesis of EBV-associated Hodgkin's lymphoma. These methods allowed us to
      identify the EBV-encoded oncoprotein LMP1 as a key element in the formation of
      Hodgkin (H-cell) and multinucleated Reed-Sternberg cells (RS-cell), the
      diagnostic tumor cell of classical Hodgkin's lymphoma (cHL). LMP1 mediates
      multinuclearity through downregulation of shelterin proteins, in particular
      telomere repeat binding factor 2 (TRF2).

PMID- 27873270
TI  - Analysis of EBV Transcription Using High-Throughput RNA Sequencing.
AB  - High-throughput sequencing of RNA is used to analyze the transcriptomes of
      viruses and cells, providing information about transcript structure and
      abundance. A wide array of programs and pipelines has been created to manage and
      interpret the abundance of data generated from high-throughput RNA sequencing
      experiments. This protocol details the use of free and open-source programs to
      align RNA-Seq reads to a reference genome, visualize read coverage and splice
      junctions, estimate transcript abundance, and evaluate differential expression of
      transcripts in different conditions. Particular concerns related to EBV and viral
      transcriptomics are addressed and access to EBV reference files is provided.

PMID- 27873271
TI  - Analysis of Viral Promoter Usage in EBV-Infected Cell Lines: A Comparison of qPCR
      Following Conventional RNA Isolation and Nuclear Run-On Assay.
AB  - To interpret the results of an epigenetic analysis in gene expression studies, it
      is essential to characterize the activity of the relevant promoters. According to
      the literature, real-time PCR assay is the most widely used method for the
      determination of latent EBV promoter usage. Here we describe two alternative
      approaches to measure the activity of viral promoters in cell lines carrying
      latent EBV episomes. The widespread typical approach relies on total cellular RNA
      isolation, whereas the nuclear run-on assay described here is based on the
      initial isolation of nuclei, followed by in vitro transcription in the presence
      of biotinylated-UTP, and purification of RNA transcripts using avidin-coated
      magnetic beads. Finally, both methods apply reverse transcription-based real-time
      PCR (i.e., quantitative polymerase chain reaction, qPCR) to quantitatively
      measure the amount of specific transcripts. We shall describe these methods step
      by step and demonstrate their use for the determination of EBER1 promoter
      activity in EBV-positive cell lines.

PMID- 27873273
TI  - Isolation and Characterization of Exosomes Released by EBV-Immortalized Cells.
AB  - Epstein-Barr virus is an oncogenic herpesvirus associated with several human
      malignancies. Although the details of the molecular steps involved in EBV
      mediated cell transformation and immune evasion are not fully known, a number of
      viral products, including EBV latent proteins and non-protein coding RNAs have
      been shown to be involved, directly or indirectly in these processes. In recent
      years, a growing body of data indicates that some viruses are able to transport
      selected products to neighboring cells and induce biological changes by
      exploiting the exosome secretory pathway. Exosomes are nanovesicles secreted by
      virtually all cell types and present in most body fluids. Here, we describe the
      protocols used in our laboratory to isolate and characterize exosomes from EBV
      infected, noninfected, and transfected cell lines.

PMID- 27873272
TI  - Analysis of Viral and Cellular MicroRNAs in EBV-Infected Cells.
AB  - MicroRNAs are small, noncoding RNAs that posttranscriptionally regulate gene
      expression. The discovery of this relatively new mode of gene regulation as well
      as studies showing the prognostic value of viral and cellular miRNAs as
      biomarkers, such as in cancer progression, has stimulated the development of many
      methods to characterize miRNAs. EBV encodes 25 viral precursor microRNAs within
      its genome that are expressed during lytic and latent infection. In addition to
      viral miRNAs, EBV infection induces the expression of specific cellular oncogenic
      miRNAs, such as miR-155, miR-146a, miR-21, and others, that can contribute to the
      persistence of latently infected cells. This chapter describes several current
      techniques used to identify and detect the expression of viral and cellular
      miRNAs in EBV-infected cells.

PMID- 27873274
TI  - Functional Analysis of Exosomes Derived from EBV-Infected Cells.
AB  - Exosomes are diverse bioactive extracellular nanovesicles excreted by different
      cell types. These tiny membrane-bound vesicles, once thought to be functionally
      insignificant, are now believed to be important vehicles for transport and
      intercellular communication. Exosomes have been shown to contain a broad range of
      molecules, from miRNAs to proteins to soluble factors. Moreover, an accumulating
      body of evidence indicates that some viruses can hijack the exosomal excretory
      pathway to influence the microenvironment surrounding the infected cells. In this
      chapter, we describe the protocols we use to examine the impact of exosomes
      isolated from EBV-infected cells on different cell types.

PMID- 27873275
TI  - Terminal Repeat Analysis of EBV Genomes.
AB  - Epstein-Barr virus (EBV) was the first human virus associated directly with human
      malignancies. During EBV infection of various host cells the double-stranded
      linear EBV DNA carried by the virions undergoes circularization. Since there are
      variable numbers of terminal repetitions (TRs) at the ends of the linear EBV
      genome, the resulting circular episomes enclose a variable number of TRs. Thus,
      in cells carrying viral episomes, the sizes of the terminal restriction enzyme
      fragments of EBV is affected by the number of TRs (Raab-Traub and Flynn Cell
      47:883-889, 1986). Southern blot analysis revealed that in monoclonal
      proliferations, arising from a single cell, there was only a single band
      representing the joined EBV termini, whereas multiple terminal restriction enzyme
      fragments that differ in size were characteristic for oligoclonal or polyclonal
      proliferations. Using suitable probes, one can distinguish the episomal form from
      the linear EBV genomes that are formed during lytic EBV replication or during
      integration into the host genome. TR analysis is a useful tool for the
      determination of EBV clonality in different clinical samples and in cell lines
      carrying EBV genomes. A single terminal restriction enzyme fragment may indicate
      EBV infection at an early phase of clonal cell proliferation, whereas polyclonal
      EBV genomes may derive from multiple infections of proliferating cells.

PMID- 27873276
TI  - Characterization of EBV Promoters and Coding Regions by Sequencing PCR-Amplified
      DNA Fragments.
AB  - DNA sequencing approaches originally developed in two directions, the chemical
      degradation method and the chain-termination method. The latter one became more
      widespread and a huge amount of sequencing data including whole genome sequences
      accumulated, based on the use of capillary sequencer systems and the application
      of a modified chain-termination method which proved to be relatively easy, fast,
      and reliable. In addition, relatively long, up to 1000 bp sequences could be
      obtained with a single read with high per-base accuracy. Although the recent
      appearance of next-generation DNA sequencing (NGS) technologies enabled high
      throughput and low cost analysis of DNA, the modified chain-terminating methods
      are often applied in research until now. In the following, we shall present the
      application of capillary sequencing for the sequence characterization of viral
      genomes in case of partial and whole genome sequencing, and demonstrate it on the
      BARF1 promoter of Epstein Barr virus (EBV).

PMID- 27873277
TI  - The Use of Chromatin Precipitation Coupled to DNA Sequencing (ChIP-Seq) for the
      Analysis of Zta Binding to the Human and EBV Genome.
AB  - Determining which components of the transcription machinery associate with the
      viral and cellular genome, and how this changes at specific stages of the viral
      life cycle is paramount to understanding how the distinct transcriptional
      programs associated with primary infection, latency, and disease are established
      and how they are reprogrammed during initiation and execution of the viral lytic
      replication cycle. Chromatin precipitations linked to next generation DNA
      sequencing (ChIP-Seq) allow for the interactions of proteins with DNA to be
      mapped across both viral and cellular genomes. This can be applied to viral and
      cellular transcription factors, coactivators and corepressors, modified histones,
      and modulators of chromatin.

PMID- 27873278
TI  - Analysis of Viral Epigenotypes Using Bisulfite Sequencing: A Detailed Protocol
      for the Crucial Bisulfite Modification and PCR Amplification Steps.
AB  - Characterization of viral DNA methylation patterns is essential to understand its
      function in viral pathogenesis. Bisulfite modification, followed by polymerase
      chain reaction (PCR) and sequencing is the most effective method for the high
      resolution methylation mapping of viral genomes. Since the bisulfite modification
      and PCR steps are the most critical ones, an optimized protocol for these two
      steps is presented, with special attention to potential pitfalls.

PMID- 27873279
TI  - Analysis of Viral Epigenotypes Using Chromatin Immunoprecipitation.
AB  - Chromatin Immunoprecipitation (ChIP) is a method used to detect DNA-protein
      interactions in vivo. ChIP has been widely applied to assess the abundance of
      various epigenetic regulators, including modified histones, in various regions of
      cellular and viral chromatin. During the procedure, DNA binding proteins are
      covalently cross-linked to DNA, and the isolated chromatin is broken into pieces
      of 300-500 bps in length on average. Thereafter, using specific antibody directed
      against the protein of interest the covalently cross-linked DNA is pulled down
      together with Protein A or G carrying beads that bind the Fc fragment of the
      antibody. After the reversal of crosslinks and DNA isolation, one may analyze the
      precipitated DNA fragments by quantitative and qualitative methods to assess the
      relative abundance of the examined protein in a region or within the genome
      studied in vivo. In addition to the analysis of transcription factor binding,
      ChIP has proved to be a reliable method to map histone modifications across
      cellular and viral epigenomes.

PMID- 27873280
TI  - Mice with Reconstituted Human Immune System Components as a Tool to Study Immune
      Cell Interactions in EBV Infection.
AB  - Recent developments in mouse models that harbor part of a human immune system
      have proved extremely valuable to study the in vivo immune response to human
      specific pathogens such as Epstein-Barr virus. Over the last decades, advances in
      immunodeficient mouse strains that can be used as recipients for human immune
      cells have greatly enhanced the use of these models. Here, we describe the
      generation of mice with reconstituted human immune system (HIS mice) using
      immunocompromised mice transplanted with human CD34+ hematopoietic stem cells. We
      will also describe how such mice, in which human immune cells are generated de
      novo, can be used to study EBV infection.

PMID- 27873281
TI  - Generation and Analysis of Humanized Mouse Model of EBV Infection.
AB  - The recent development of severely immunodeficient mouse strains enabled the
      production of new-generation humanized mice, in which major components of the
      human immune system are reconstituted. These new-generation humanized mice can be
      infected with human pathogenic viruses that do not infect regular mice and target
      cells of the hematoimmune system. Here we describe the method for preparing
      humanized mice, infecting them with EBV, and for their virological and
      immunological analyses. The results obtained from our own mouse models are
      briefly described.

PMID- 27873282
TI  - EBV-Directed T Cell Therapeutics for EBV-Associated Lymphomas.
AB  - Epstein Barr virus (EBV) is a human gamma herpes virus that establishes latency
      in B cells after primary infection. EBV generally only causes a mild, self
      limiting viral illness but is also associated with several malignancies including
      posttransplantation lymphoproliferative disorder in the immunosuppressed host as
      well as Hodgkin and non-Hodgkin lymphoma in the immune competent host. The
      expression of EBV antigens by lymphoma has important applications as targets for
      adoptive T cell therapy. However, as many lymphomas only express subdominant EBV
      antigens that are less immunogenic, novel strategies are needed to manufacture
      EBV-specific T cell products specific for Latent Membrane Protein 1 (LMP1) and
      LMP2, which are expressed in lymphomas with type II and III latency. While
      several techniques for manufacturing EBV-CTLs are described in the literature,
      this chapter focuses on one method for generating Good Manufacturing Practice
      (GMP)-compliant EBV-specific T cell products that are enriched with LMP1 and
      LMP2.

PMID- 27873283
TI  - A method to enhance 2D ion chamber array patient specific quality assurance for
      IMRT.
AB  - Gamma index comparison has been established as a method for patient specific
      quality assurance in IMRT. Detector arrays can replace radiographic film systems
      to record 2D dose distributions and fulfill quality assurance requirements. These
      electronic devices present spatial resolution disadvantages with respect to
      films. This handicap can be partially overcome with a multiple acquisition
      sequence of adjacent 2D dose distributions. The detector spatial response
      influence can also be taken into account through the convolution of the
      calculated dose with the detector spatial response. A methodology that employs
      both approaches could allow for enhancements of the quality assurance procedure.
      35 beams from different step and shoot IMRT plans were delivered on a phantom. 2D
      dose distributions were recorded with a PTW-729 ion chamber array for individual
      beams, following the multiple acquisition methodology. 2D dose distributions were
      also recorded on radiographic films. Measured dose distributions with films and
      with the PTW-729 array were processed with the software RITv5.2 for Gamma index
      comparison with calculated doses. Calculated dose was also convolved with the ion
      chamber 2D response and the Gamma index comparisons with the 2D dose distribution
      measured with the PTW-729 array was repeated. 3.7 +/- 2.7% of points surpassed
      the accepted Gamma index when using radiographic films compared with calculated
      dose, with a minimum of 0.67 and a maximum of 13.27. With the PTW-729 multiple
      acquisition methodology compared with calculated dose, 4.1 +/- 1.3% of points
      surpassed the accepted Gamma index, with a minimum of 1.44 and a maximum of
      11.26. With the PTW- multiple acquisition methodology compared with convolved
      calculated dose, 2.7 +/- 1.3% of points surpassed the accepted Gamma index, with
      a minimum of 0.42 and a maximum of 5.75. The results obtained in this work
      suggest that the comparison of merged adjacent dose distributions with convolved
      calculated dose represents an enhancement in the methodology for IMRT patient
      specific quality assurance with the PTW-729 ion chamber array.

PMID- 27873284
TI  - A case of acute myocardial infarction due to cardiovascular syphilis with aortic
      regurgitation and bilateral coronary ostial stenosis.
AB  - We report an interesting case of a 66-year-old man with acute myocardial
      infarction (AMI) with bilateral coronary ostial stenosis cardiovascular syphilis
      complicated by aortic regurgitation (AR). A 12-lead electrocardiogram and blood
      tests on arrival suggested AMI, and echocardiography showed moderate AR.
      Emergency coronary angiography showed bilateral coronary ostial stenosis. The
      patient underwent emergency surgical treatment, coronary artery bypass grafting,
      and aortic valve replacement with a bioprosthetic valve. On arrival, rapid plasma
      reagin and Treponema pallidum hemagglutination tests were 172.2- and 1187.5-fold,
      respectively. These results suggested cardiovascular syphilis, which was
      confirmed by pathological findings. The postoperative course was uneventful and
      the patient was transferred to another hospital on postoperative day 25. This
      patient received intravenous penicillin for 2 weeks and subsequently oral
      amoxicillin. When both AR and coronary ostial stenosis are found, it is necessary
      to consider the presence of cardiovascular syphilis.

PMID- 27873286
TI  - Carbon Nanotube Thin Film Transistors for Flat Panel Display Application.
AB  - Carbon nanotubes (CNTs) are promising materials for both high performance
      transistors for high speed computing and thin film transistors for
      macroelectronics, which can provide more functions at low cost. Among
      macroelectronics applications, carbon nanotube thin film transistors (CNT-TFT)
      are expected to be used soon for backplanes in flat panel displays (FPDs) due to
      their superior performance. In this paper, we review the challenges of CNT-TFT
      technology for FPD applications. The device performance of state-of-the-art CNT
      TFTs are compared with the requirements of TFTs for FPDs. Compatibility of the
      fabrication processes of CNT-TFTs and current TFT technologies are critically
      examined. Though CNT-TFT technology is not yet ready for backplane production
      line of FPDs, the challenges can be overcome by close collaboration between
      research institutes and FPD manufacturers in the short term.

PMID- 27873285
TI  - Prescription Drug Use and Polypharmacy Among Medicaid-Enrolled Adults with
      Autism: A Retrospective Cross-Sectional Analysis.
AB  - BACKGROUND: A lack of gold standard treatment for autism spectrum disorders
      (ASD), no clear ASD management guidelines, and lack of evidence-based
      pharmacological interventions other than aripiprazole and risperidone elevate the
      risk of off-label prescribing and adverse effects among individuals with ASD,
      more so among adults. OBJECTIVE: The aim of this study was to identify and
      compare the types of prescription drug use, rates of polypharmacy, and
      characteristics associated with polypharmacy among adults with and without ASD in
      a retrospective cross-sectional analysis of a three-state Medicaid Analytic
      eXtract database (2000-2008). METHODS: Adults aged 22-64 years with ASD (ICD9-CM
      code: 299.xx) were propensity score-matched to 'no ASD' controls by age, sex, and
      race. General polypharmacy (>=6 unique classes of prescription drugs in a year)
      and psychotropic polypharmacy (>=3 unique prescription drug classes of
      psychotropic medications within a 90-day period) were the main study outcomes.
      Chi-square tests for rates, t tests for mean number of claims, and multivariate
      logistic regressions for likelihood of prescription drug use and polypharmacy
      were run. RESULTS: Annually, almost 75% of adults with ASD had >20 prescription
      drug claims compared with 33% of adults without ASD. Around 85% of adults with
      ASD used at least one psychotropic drug class compared with 42% of adults without
      ASD. Highly common psychotropics were antipsychotics (66%ASD vs 20%noASD),
      anticonvulsants (59%ASD vs 20%noASD), and anxiolytics/hypnotics/sedatives (21%ASD
      vs 11%noASD). Other than psychotropics, many adults with ASD used medical
      prescription drugs such as antimicrobials (47%), dermatologic agents (48%),
      respiratory agents (38%), gastrointestinal agents (31%), alternative medications
      (25%), antiparkinsonian agents (22.6%), antihyperlipidemics/statins (7.3%), and
      immunologics (2.0%). Rates of general (48%ASD vs 32%noASD) and psychotropic
      polypharmacy (19%ASD vs 6%noASD) were significantly higher in the ASD group.
      CONCLUSION: Prescription drug use and polypharmacy rates among adults with ASD
      are substantially higher than those in an age-, sex-, and race-matched cohort of
      adults without ASD. Adults with ASD frequently use therapeutic treatments other
      than psychotropics. Healthcare providers, who usually report low confidence in
      treating patients with ASD, should play an active role in constant monitoring of
      prescription drug use patterns and patient response to interventions. Prescribers
      and caregivers are encouraged to make decisions after weighing the benefits and
      risks associated with a pharmacological treatment. Further investigations into
      the common use of any alternative treatments that can affect a patient's response
      to core treatments should also be conducted.

PMID- 27873287
TI  - Non-Invasive and Non-Destructive Examination of Artistic Pigments, Paints, and
      Paintings by Means of X-Ray Methods.
AB  - Recent studies are concisely reviewed, in which X-ray beams of (sub)micrometre to
      millimetre dimensions have been used for non-destructive analysis and
      characterization of pigments, minute paint samples, and/or entire paintings from
      the seventeenth to the early twentieth century painters. The overview presented
      encompasses the use of laboratory and synchrotron radiation-based instrumentation
      and deals with the use of several variants of X-ray fluorescence (XRF) as a
      method of elemental analysis and imaging, as well as with the combined use of X
      ray diffraction (XRD) and X-ray absorption spectroscopy (XAS). Microscopic XRF is
      a variant of the method that is well suited to visualize the elemental
      distribution of key elements, mostly metals, present in paint multi-layers, on
      the length scale from 1 to 100 MUm inside micro-samples taken from paintings. In
      the context of the characterization of artists' pigments subjected to natural
      degradation, the use of methods limited to elemental analysis or imaging usually
      is not sufficient to elucidate the chemical transformations that have taken
      place. However, at synchrotron facilities, combinations of MU-XRF with related
      methods such as MU-XAS and MU-XRD have proven themselves to be very suitable for
      such studies. Their use is often combined with microscopic Fourier transform
      infra-red spectroscopy and/or Raman microscopy since these methods deliver
      complementary information of high molecular specificity at more or less the same
      length scale as the X-ray microprobe techniques. Since microscopic investigation
      of a relatively limited number of minute paint samples, taken from a given work
      of art, may not yield representative information about the entire artefact,
      several methods for macroscopic, non-invasive imaging have recently been
      developed. Those based on XRF scanning and full-field hyperspectral imaging
      appear very promising; some recent published results are discussed.

PMID- 27873288
TI  - Cardioprotective Effect of Aloe vera Biomacromolecules Conjugated with Selenium
      Trace Element on Myocardial Ischemia-Reperfusion Injury in Rats.
AB  - The present study was undertaken to evaluate the cardioprotection potential and
      underlying molecular mechanism afforded by a selenium (Se) polysaccharide (Se
      AVP) from Aloe vera in the ischemia-reperfusion (I/R) model of rats in vivo.
      Myocardial I/R injury was induced by occluding the left anterior descending
      coronary artery (LAD) for 30 min followed by 2-h continuous reperfusion.
      Pretreatment with Se-AVP (100, 200, and 400 mg/kg) attenuated myocardial damage,
      as evidenced by reduction of the infarct sizes, increase in serum and myocardial
      endogenous antioxidants (superoxide dismutase (SOD), glutathione peroxidase
      (GSH), and catalase (CAT)), and decrease in the malondialdehyde (MDA) level in
      the rats suffering I/R injury. This cardioprotective activity afforded by Se-AVP
      is further supported by the decreased levels of cardiac marker enzymes creatine
      kinase (CK) and lactate dehydrogenase (LDH), as well as the rise of myocardial
      Na+-K+-ATPase and Ca2+-Mg2+-ATPase activities in I/R rats. Additionally,
      cardiomyocytic apoptosis was measured by terminal-deoxynucleotidyl transferase
      mediated nick end labeling (TUNEL) staining and the result showed that the
      percent of TUNEL-positive cells in myocardium of Se-AVP-treated groups was lower
      than I/R rats. In conclusion, we clearly demonstrated that Se-AVP had a
      protective effect against myocardial I/R injury in rats by augmenting endogenous
      antioxidants and protecting rat hearts from oxidative stress-induced myocardial
      apoptosis.

PMID- 27873289
TI  - The Effect of Ketogenic Diet on Serum Selenium Levels in Patients with
      Intractable Epilepsy.
AB  - The aim of the present study was to evaluate serum selenium levels in children
      receiving olive oil-based ketogenic diet (KD) for intractable seizures for at
      least 1 year. Out of 320 patients who were initiated on KD, patients who
      continued receiving KD for at least 12 months were enrolled. Sixteen patients who
      had selenium deficiency at the time of starting KD were excluded. Finally, a
      total of 110 patients (mean age 7.3 +/- 4.2 years) were included. Serum selenium
      levels were measured at baseline and at 3, 6, and 12 months after treatment
      initiation by using atomic absorption spectroscopy. Selenium deficiency was
      defined as a serum selenium level <48 MUg/L at each visit. Repeated measure ANOVA
      with post hoc Bonferroni correction was used for data analysis. Mean duration of
      KD was 15.3 +/- 4.3 months. Mean serum selenium levels were significantly lower
      at 6 and 12 months of KD treatment (66.2 +/- 23.3 and 57.2 +/- 16.2 MUg/L,
      respectively) compared to pre-treatment levels (79.3 +/- 25.7 MUg/L) (p = 0.001).
      On the other hand, selenium levels did not show any significant difference at 3
      months of KD treatment (70.0 +/- 21.2 MUg/L) compared to baseline levels (p =
      0.076). A total of 54 patients (49.1%) were diagnosed with selenium deficiency,
      and oral selenium medication was initiated for these patients. No relevant
      clinical findings were detected, and echocardiographic findings were normal in
      all patients. The decline of the serum selenium concentrations after 6 and 12
      months of ketogenic diet suggests that patients on this highly prescriptive
      dietary treatment need close monitoring of this trace element.

PMID- 27873290
TI  - Aims and structure of the German Research Consortium BipoLife for the study of
      bipolar disorder.
AB  - BACKGROUND: Bipolar disorder is a severe and heterogeneous mental disorder.
      Despite great advances in neuroscience over the past decades, the precise
      causative mechanisms at the transmitter, cellular or network level have so far
      not been unraveled. As a result, individual treatment decisions cannot be tailor
      made and the uncertain prognosis is based on clinical characteristics alone.
      Although a subpopulation of patients have an excellent response to
      pharmacological monotherapy, other subpopulations have been less well served by
      the medical system and therefore require more focused attention. In particular
      individuals at high risk of bipolar disorder, young patients in the early stages
      of bipolar disorder, patients with an unstable highly relapsing course and
      patients with acute suicidal ideation have been identified as those in need.
      STRUCTURE: A research consortium of ten universities across Germany has therefore
      implemented a 4 year research agenda including three randomized controlled
      trials, one epidemiological trial and one cross-sectional trial to address these
      areas of unmet needs. The topics under investigation will be the improvement of
      early recognition, specific psychotherapy, and smartphones as an aid for early
      episode detection and biomarkers of lithium response. A subset of patients will
      be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and
      biomaterials (genomics, transcriptomics). CONCLUSIONS: This article aims to
      outline the rationale, design, and methods of these individual studies.

PMID- 27873292
TI  - ICU management based on PiCCO parameters reduces duration of mechanical
      ventilation and ICU length of stay in patients with severe thoracic trauma and
      acute respiratory distress syndrome.
AB  - BACKGROUND: This study aimed to assess whether a management algorithm using data
      obtained with a PiCCO system can improve clinical outcomes in critically ill
      patients with acute respiratory distress syndrome (ARDS). RESULTS: The PaO2/FiO2
      ratio increased over time in both groups, with a sharper increase in the PiCCO
      group. There was no difference in 28-day mortality (3.2 vs. 3.6%, P = 0.841).
      Days on mechanical ventilation (3 vs. 5 days, P = 0.002) and ICU length of stay
      (6 vs. 11 days, P = 0.004) were significantly lower in the PiCCO group than in
      the CVP group. Treatment costs were lower in the PiCCO group than in the CVP
      group. Multivariate logistic regression model showed that the monitoring method
      (PiCCO vs. CVP) was independently associated with the length of ICU stay [odds
      ratio (OR) 3.16, 95% confidence interval (95% CI) 1.55-6.63, P = 0.001], as well
      as shock (OR 3.41, 95% CI 1.74-6.44, P = 0.002), shock and ARDS (OR 3.46, 95% CI
      1.79-6.87, P = 0.002), and APACHE II score (OR 1.17, 95% CI 1.02-1.86, P =
      0.014). CONCLUSIONS: This study investigated the usefulness of the PiCCO system
      in improving outcomes for patient with severe thoracic trauma and ARDS and
      provided new evidence for fluid management in critical care settings.

PMID- 27873294
TI  - Antiepileptic Drugs for Patients with Intracerebral Hemorrhage: A Meta-Analysis.
AB  - AIM: Whether an antiepileptic drug (AED) should be prescribed for intracerebral
      hemorrhage (ICH) patients is a matter in dispute, and recent studies have come up
      with different or even opposite views. A meta-analysis on this issue has not been
      performed. The goal of this meta-analysis was to study antiepileptic drugs"
      effects on early seizure occurrence and outcome for ICH patients. MATERIAL AND
      METHODS: We searched the PubMed, Ovid, and Cochrane library until December 2015
      to identify relevant articles. A meta-analysis was conducted to evaluate the
      overall effect with random-effects or fixed-effects models. RESULTS: Four
      articles consisting of one randomized controlled trial and three cohort studies
      met the included criteria. For the occurrence of early seizure, antiepileptic
      drugs showed the ability to reduce the risk, but reached no statistical
      significance (OR=0.71; 95% CI, 0.38-1.34; test for overall effect Z=1.06,
      p=0.29). No association between antiepileptic drug use and poor outcome was found
      (OR=1.95; 95% CI, 0.56-6.79; test for overall effect Z=1.06, P=0.29), but
      heterogeneity was present. CONCLUSION: Summarizing published studies, the AED use
      did not reduce early seizure occurrence statistically but a population with high
      risk factors of early seizure is likely to benefit from AEDs. Besides, AED use
      was not associated with poor outcome. We suggest AED use for ICH patients with
      high-risk factors of seizure, but not generally.

PMID- 27873293
TI  - Supraorbital Keyhole Microsurgical Fenestration of Symptomatic Temporal Arachnoid
      Cysts in Children: Advantages and Limitations.
AB  - AIM: To investigate the impact of endoscope-assisted microsurgical fenestration
      on temporal arachnoid cysts, and to determine the advantages and limitations of
      the technique. MATERIAL AND METHODS: Twenty-five children with symptomatic
      temporal arachnoid cysts were operated via eyebrow supraorbital keyhole
      microsurgical fenestration targeting the medial cyst wall. Preoperative magnetic
      resonance imaging (MRI) of the brain was done for all patients. RESULTS:
      Preoperative clinical presentation of the patients included headache (80%),
      nausea & vomiting (64%), drug resistant epilepsy (52%), macrocephaly (12%)
      papilledema (28%), motor weakness in the form of right-sided hemiparesis (12%)
      and cranial nerve palsy. Postoperative complete subsidence of headache was noted
      in 50%, while 20% remained unchanged. Drug resistant epilepsy improved in 69% of
      the patients. Postoperative MRI showed initial decrease in cyst volume as early
      as 3 months, only in a range of 5-12% volume reduction, and the late follow-up
      done at 6 and 18 months continued to show further reduction reported to be
      significant (p < 0.001). Transient subgaleal cerebrospinal fluid (CSF) collection
      was the most common complication (20%). Only 1 patient experienced CSF leak
      mandating cysto-peritoneal shunting. Conclusion: Eyebrow supraorbital keyhole
      microsurgical fenestration for temporal arachnoid cysts can be performed with a
      fairly low risk of complications and yields a favorable improvement in clinical
      and neuroimaging outcomes.

PMID- 27873295
TI  - Colleges and universities sticking to their guns?
AB  - Firearm possession on college and university campuses remains a volatile public
      policy issue among policymakers, legislators, scholars, and administrators. Given
      the American federal governmental structure, many states have developed
      legislative approaches to "carry on campus" policies throughout the years that
      align with federal law. This study explores the diversity of state approaches and
      nuances of "carry on campus" throughout recent years and current state
      legislation under consideration. The implications of "carry on campus"
      legislation vary on college campuses, depending on applicable state law; however,
      some general dynamics apply to all.

PMID- 27873291
TI  - Prediction of non-recovery from ventilator-demanding acute respiratory failure,
      ARDS and death using lung damage biomarkers: data from a 1200-patient critical
      care randomized trial.
AB  - BACKGROUND: It is unclear whether biomarkers of alveolar damage (surfactant
      protein D, SPD) or conductive airway damage (club cell secretory protein 16,
      CC16) measured early after intensive care admittance are associated with one
      month clinical respiratory prognosis. If patients who do not recover respiratory
      function within one month can be identified early, future experimental lung
      interventions can be aimed toward this high-risk group. We aimed to determine, in
      a heterogenous critically ill population, whether baseline profound alveolar
      damage or conductive airway damage has clinical respiratory impact one month
      after intensive care admittance. METHODS: Biobank study of biomarkers of alveolar
      and conductive airway damage in intensive care patients was conducted. This was a
      sub-study of 758 intubated patients from a 1200-patient randomized trial. We
      split the cohort into a "learning cohort" and "validating cohort" based on
      geographical criteria: northern sites (learning) and southern sites (validating).
      RESULTS: Baseline SPD above the 85th percentile in the "learning cohort"
      predicted low chance of successful weaning from ventilator within 28 days
      (adjusted hazard ratio 0.6 [95% CI 0.4-0.9], p = 0.005); this was confirmed in
      the validating cohort. CC16 did not predict the endpoint. The absolute risk of
      not being successfully weaned within the first month was 48/106 (45.3%) vs.
      175/652 (26.8%), p < 0.0001 (high SPD vs. low SPD). The chance of being "alive
      and without ventilator >=20 days within the first month" was lower among patients
      with high SPD (adjusted OR 0.2 [95% CI 0.2-0.4], p < 0.0001), confirmed in the
      validating cohort, and the risk of ARDS was higher among patients with high SPD
      (adjusted OR 3.4 [95% CI 1.0-11.4], p = 0.04)-also confirmed in the validating
      cohort. CONCLUSION: Early profound alveolar damage in intubated patients can be
      identified by SPD blood measurement at intensive care admission, and high SPD
      level is a strong independent predictor that the patient suffers from ARDS and
      will not recover independent respiratory function within one month. This
      knowledge can be used to improve diagnostic and prognostic models and to identify
      the patients who most likely will benefit from experimental interventions aiming
      to preserve alveolar tissue and therefore respiratory function. Trial
      registration This is a sub-study to the Procalcitonin And Survival Study (PASS),
      Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.

PMID- 27873297
TI  - Emergency notifications: Twentieth century or twenty-first?
AB  - This article explores one area of the decision-making process for emergency
      managers: when and how to issue a public notification. For certain emergencies, a
      plan is in place. In other scenarios, a notification decision must be made that
      could be the difference between life and death. Perhaps the best known of these
      options is the mass media Emergency Alert System. However, newer options may
      provide better ways to inform a potentially affected population. Through
      interviews and literature reviews, this article will explore the choices
      available and the need for a coherent decision to be made in a difficult
      environment.

PMID- 27873296
TI  - Emergency preparedness of veterans and nonveterans.
AB  - This study examined statistical differences in levels of disaster preparedness
      between former members of the US Armed Forces (veterans) and civilians
      (nonveterans). It was hypothesized that veterans would exhibit a higher degree of
      disaster preparedness as compared to their nonveteran counterparts as a
      consequence of their training and life experience. Furthermore, if this were
      proven to be valid, the finding would identify this cohort as an ideal target
      audience for emergency and disaster preparedness education efforts. A four-page
      survey consisting principally of closed-ended questions about emergency
      preparedness was written to measure these differences. Most of the questions
      required respondents to rank their answers according to a five-step Likert Scale.
      The survey could be completed either in hard copy or online from September 2014
      to January 2015. Ultimately, 113 surveys were returned for evaluation. Of those
      respondents, 62 were veterans and 51 were nonveterans. The responses were
      analyzed using one-way analysis of variance tests for statistical significance
      using the 95 percent confidence standard for each tested value. The results
      support that veterans are more prepared for domestic emergencies than
      nonveterans. In addition, veterans were more willing to provide leadership and
      direction to others in an effort to assist emergency managers in responding to
      domestic disasters. It is for these reasons that emergency managers should
      consider targeting veterans for disaster preparedness training to help ensure
      effective and efficient responses to emergencies.

PMID- 27873298
TI  - Place attachment and disasters: Knowns and unknowns.
AB  - When considering the factors important for disaster recovery, one must consider
      the attachment individuals have toward their living area. This article reviews
      and synthesizes the current literature on the determinants of place attachment in
      the context of postdisaster recovery. Although the majority of the reviewed
      articles focused on disaster recovery, there were some which had a broader scope
      and were included due to their importance. This research categorizes the
      determinants of place attachment into four categories: demographic,
      socioeconomic, spatial, and psychosocial. Age, ethnicity, and religion were
      grouped under the category of demographics. Job status, education, and property
      ownership were categorized under the socioeconomic category. Attachment to home,
      neighborhood, and city, together with attachment to rural and urban areas, were
      grouped under the spatial category. Finally, mental health status and community
      attachment were classified under the psychosocial heading. Based on the outcome
      of the aforementioned synthesis, this article develops a conceptual framework to
      guide future research.

PMID- 27873299
TI  - Using the Manchester triage system for refusing nonurgent patients in the
      emergency department: A 30-day outcome study.
AB  - OBJECTIVE: To evaluate the long-term outcomes and satisfaction of nonurgent
      patients who seek care in the emergency department (ED) and are diverted to
      primary health services (PHS). METHODS: Data were collected from 264 nonurgent
      patients diverted from the ED of a tertiary public university hospital in Sao
      Paulo, Brazil. The nonurgent patient definition was performed by Manchester
      triage system version II (MTS-II) associated to medical interview in the triage
      service. Satisfaction levels were evaluated by telephone interviews. The outcomes
      were assessed within 30 days after the ED visit. RESULTS: Based on the MTS-II,
      56.4 percent of the diverted patients were classified as green, 34.3 percent as
      blue, and 9.3 percent as white. Only one patient required a hospital admission
      and no deaths were registered within 30 days after ED diversion. After diversion,
      the majority of patients searched for PHS (62.7 percent), 14.4 percent sought out
      other EDs, and 22.9 percent did not seek out any other health services. Regarding
      patient satisfaction, 61.9 percent evaluated the triage team as fair, good, or
      very good. CONCLUSIONS: Our study suggests that diverting nonurgent patients from
      the ED to PHS may be carried out in a hierarchic system like the Brazilian public
      healthcare system. The MTS-II can be a useful triage system to support physician
      in the diverting process. In addition, patient satisfaction with the refusing was
      reasonable. Future studies should be designed to evaluate patient safety outcomes
      in a larger sample and in different healthcare systems.

PMID- 27873300
TI  - Local checkpoint inhibition of CTLA-4 as a monotherapy or in combination with
      anti-PD1 prevents the growth of murine bladder cancer.
AB  - Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in
      metastatic cancer patients. However, patients treated with CTLA-4 blockade have
      suffered from immune-related adverse events, most likely due to the breadth of
      the induced T-cell activation. Here, we investigated the efficacy of a local low
      dose anti-CTLA-4 administration for treatment of subcutaneous or orthotopic
      murine bladder 49 (MB49) bladder carcinoma in C57BL/6 mice. When MB49 tumors were
      grown s.c., peritumoral (p.t.) injection of anti-CTLA-4 treatment was equally
      effective as intravenous or s.c. (nontumor bearing flank) administration.
      Notably, p.t. injection was associated with lower circulating antibody levels and
      decreased IL-6 serum levels as compared to systemic treatment. Ultrasound-guided
      intratumoral anti-CTLA-4 antibody treatment of orthotopically growing MB49 tumors
      resulted in tumor regression, with more than tenfold reduction in systemic
      antibody levels as compared to i.v. or s.c. administration, in line with the
      compartmentally restrained nature of the bladder. Local anti-CTLA-4 therapy in
      combination with anti-PD-1 therapy resulted in complete responses, superior to
      each therapy alone. In addition, p.t. anti-CTLA-4 therapy was potentiated by
      depletion of regulatory T cells. Our results demonstrate that local anti-CTLA-4
      antibody therapy is equally effective as systemic administration, but reduces
      systemic antibody levels and cytokine release, and enhances the response to anti
      PD1 therapy.

PMID- 27873301
TI  - Regarding 'Frontal fibrosing alopecia: possible association with leave-on facial
      skincare products and sunscreens; a questionnaire study'.

PMID- 27873302
TI  - Ultrasonographic findings can identify 'pseudoprogression' under nivolumab
      therapy.
AB  - 'Pseudoprogression' is often seen in patients with melanomas who are treated with
      immune checkpoint inhibitors such as nivolumab or ipilimumab. We sometimes
      evaluate metastatic lesions by imaging tests such as computed tomography (CT) or
      positron emission tomography-CT. 'Pseudoprogression' usually occurs upon the
      initial administration, which may make it difficult for the physician to
      determine the disease condition. In our two cases of metastatic melanoma treated
      with nivolumab (antiprogrammed cell death-1 antibody), we examined the
      ultrasonography (US) of target lesions that could be accessed from the body
      surface, such as those of the regional lymph node or subcutaneous metastasis. In
      both cases, the US revealed a lesion approximately 10% greater in size after 40
      50 days of nivolumab administration, even though the blood flow inside the tumour
      was reduced by about 20% within 50 days. From about 100 days after blood flow
      reduction was detected by US, the tumours began to decrease in size. However,
      contrast CT was unable to detect the association between tumour size and tumour
      blood flow. The present cases suggest that US could be a powerful tool for
      differentiating between 'pseudoprogression' and real progressive disease in
      patients treated with cancer immunotherapies such as those involving immune
      checkpoint inhibitors. The misdiagnosis of progressive disease can lead to
      unnecessary alterations to the current treatment. Therefore, the US findings in
      our study could be clinically useful and educational for physicians.

PMID- 27873303
TI  - Cutis laxa acquisita: novel insights into impaired elastic fibre regeneration.

PMID- 27873304
TI  - Stent-induced tracheal stenosis can be predicted by IL-8 expression in rabbits.
AB  - BACKGROUND: Bare metal stents may cause complications like fibrous encapsulation,
      granulation and tracheal stenosis. We investigated the behaviour of three
      commercially available stents in vivo (rabbits) and in vitro (coculture of those
      stents with epithelial and fibroblast cell lines). Also, we investigated whether
      development of tracheal stenosis could be predicted by any biological marker.
      MATERIALS AND METHODS: The tracheae of 30 rabbits were implanted with either
      nitinol stents, with or without paclitaxel elution, or a cobalt-based stent. An
      additional ten rabbits underwent mock implantation (controls). Serial peripheral
      venous blood samples were taken throughout the study, and several cytokines
      measured. Animals were euthanized on day 90, with immediate tracheal endoscopy
      and lavage performed, then necropsy. RESULTS: Rabbits with cobalt-based stent
      exhibited more inflammation and the highest stenosis incidence, with reduced
      survival. Both in vivo and in vitro, this stent induced higher IL-8 levels than
      nitinol stents. Most important, the presence of stent-induced tracheal stenosis
      was closely associated to increase in IL-8 expression in blood just 1 day after
      tracheal stent implantation: a 1.19-fold increase vs. baseline had 83%
      sensitivity, 83% specificity, 77% positive predictive value, 88% negative
      predictive value and 83% accuracy to predict development of stenosis.
      CONCLUSIONS: The cobalt-based stent had the highest incidence of tracheal
      inflammation and stenosis. On the other hand, the paclitaxel-eluting nitinol
      stent did not prevent those complications and provoked a marked reaction compared
      with the bare nitinol stent. Early increase in IL-8 expression in blood after
      stent implantation could predict development of tracheal stenosis in rabbits.

PMID- 27873305
TI  - Adjusting Health Expenditures for Inflation: A Review of Measures for Health
      Services Research in the United States.
AB  - OBJECTIVE: To provide guidance on selecting the most appropriate price index for
      adjusting health expenditures or costs for inflation. DATA SOURCES: Major price
      index series produced by federal statistical agencies. STUDY DESIGN: We compare
      the key characteristics of each index and develop suggestions on specific indexes
      to use in many common situations and general guidance in others. DATA
      COLLECTION/EXTRACTION METHODS: Price series and methodological documentation were
      downloaded from federal websites and supplemented with literature scans.
      PRINCIPAL FINDINGS: The gross domestic product implicit price deflator or the
      overall Personal Consumption Expenditures (PCE) index is preferable to the
      Consumer Price Index (CPI-U) to adjust for general inflation, in most cases. The
      Personal Health Care (PHC) index or the PCE health-by-function index is generally
      preferred to adjust total medical expenditures for inflation. The CPI medical
      care index is preferred for the adjustment of consumer out-of-pocket expenditures
      for inflation. A new, experimental disease-specific Medical Care Expenditure
      Index is now available to adjust payments for disease treatment episodes.
      CONCLUSIONS: There is no single gold standard for adjusting health expenditures
      for inflation. Our discussion of best practices can help researchers select the
      index best suited to their study.

PMID- 27873307
TI  - Considerations on the precedence of the scenes, the contact barrier and the
      separation of conscious and unconscious.
AB  - In this essay the term 'scene' which has been developed in the German
      psychoanalytic discussion, is confronted with the terms 'total situation' and
      'psychoanalytic field', showing common features as well as differences.
      Thereafter four child observations are presented, through which light is thrown
      onto the scenic structures which make the foundations of early experience. In the
      precedence of scenes those structures are omnipresent whereas subjectivity only
      gradually builds up. It is shown how the development of subjectivity and the
      differentiation of consciousness and unconscious go along with overcoming the
      precedence of scenes, by breaking them up and reorganizing them. Thus scenes can
      become metaphors, which are used for 'translating' experience and for building up
      the contact barrier.

PMID- 27873306
TI  - Activated leukocyte cell adhesion molecule (ALCAM) is a marker of recurrence and
      promotes cell migration, invasion, and metastasis in early-stage endometrioid
      endometrial cancer.
AB  - Endometrial cancer is the most common gynaecological cancer in western countries,
      being the most common subtype of endometrioid tumours. Most patients are
      diagnosed at an early stage and present an excellent prognosis. However, a number
      of those continue to suffer recurrence, without means of identification by risk
      classification systems. Thus, finding a reliable marker to predict recurrence
      becomes an important unmet clinical issue. ALCAM is a cell-cell adhesion molecule
      and member of the immunoglobulin superfamily that has been associated with the
      genesis of many cancers. Here, we first determined the value of ALCAM as a marker
      of recurrence in endometrioid endometrial cancer by conducting a retrospective
      multicentre study of 174 primary tumours. In early-stage patients (N = 134),
      recurrence-free survival was poorer in patients with ALCAM-positive compared to
      ALCAM-negative tumours (HR 4.237; 95% CI 1.01-17.76). This difference was more
      significant in patients with early-stage moderately-poorly differentiated tumours
      (HR 9.259; 95% CI 2.12-53.47). In multivariate analysis, ALCAM positivity was an
      independent prognostic factor in early-stage disease (HR 6.027; 95% CI 1.41
      25.74). Then we demonstrated in vitro a role for ALCAM in cell migration and
      invasion by using a loss-of-function model in two endometrial cancer cell lines.
      ALCAM depletion resulted in a reduced primary tumour size and reduced metastatic
      local spread in an orthotopic murine model. Gene expression analysis of ALCAM
      depleted cell lines pointed to motility, invasiveness, cellular assembly, and
      organization as the most deregulated functions. Finally, we assessed some of the
      downstream effector genes that are involved in ALCAM-mediated cell migration;
      specifically FLNB, TXNRD1, and LAMC2 were validated at the mRNA and protein
      level. In conclusion, our results highlight the potential of ALCAM as a recurrent
      biomarker in early-stage endometrioid endometrial cancer and point to ALCAM as an
      important molecule in endometrial cancer dissemination by regulating cell
      migration, invasion, and metastasis. Copyright (c) 2016 Pathological Society of
      Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 27873309
TI  - Passages 2017.

PMID- 27873308
TI  - Adjuvant platinum-based chemotherapy for early stage cervical cancer.
AB  - BACKGROUND: This is the second updated version of the original Cochrane review
      published in the Cochrane Library 2009, Issue 3. Most women with early cervical
      cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We
      performed this review originally because it was unclear whether cisplatin-based
      chemotherapy after surgery, radiotherapy or both, in women with early stage
      disease with risk factors for recurrence, was associated with additional survival
      benefits or risks. OBJECTIVES: To evaluate the effectiveness and safety of
      adjuvant platinum-based chemotherapy after radical hysterectomy, radiotherapy, or
      both in the treatment of early stage cervical cancer. SEARCH METHODS: For the
      original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the
      Cochrane Library 2009, Issue 1), MEDLINE, Embase, LILACS, BIOLOGICAL ABSTRACTS
      and CancerLit, the National Research Register and Clinical Trials register, with
      no language restriction. We handsearched abstracts of scientific meetings and
      other relevant publications. We extended the database searches to November 2011
      for the first update and to September 2016 for the second update. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based
      chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant
      chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at
      least one risk factor for recurrence. DATA COLLECTION AND ANALYSIS: Two review
      authors extracted data independently. Meta-analysis was performed using a random
      effects model, with death and disease progression as outcomes. MAIN RESULTS: For
      this second updated version we identified only one small trial reporting grade 4
      toxicity results, without disease-free or overall survival data with a median
      follow-up of 16 months.From the first updated version, we identified three trials
      that were ongoing, and remain so in 2016.Four trials including 401 women with
      evaluable results with early cervical cancer were included in the meta-analyses.
      The median follow-up period in these trials ranged from 29 to 42 months. All
      women had undergone surgery first. Three trials compared chemotherapy combined
      with radiotherapy versus radiotherapy alone; and one trial compared chemotherapy
      followed by radiotherapy versus radiotherapy alone. It was not possible to
      perform subgroup analyses by stage or tumour size.Compared with adjuvant
      radiotherapy, chemotherapy combined with radiotherapy significantly reduced the
      risk of death (two trials, 297 women; hazard ratio (HR) = 0.56, 95% confidence
      interval (CI): 0.36 to 0.87) and disease progression (two trials, 297 women; HR =
      0.47, 95% CI 0.30 to 0.74), with no heterogeneity between trials (I2 = 0% for
      both meta-analyses). Acute grade 4 toxicity occurred significantly more
      frequently in the chemotherapy plus radiotherapy group than in the radiotherapy
      group (three trials, 321 women; risk ratio (RR) 6.26, 95% CI 2.50 to 15.67). We
      considered the evidence for all three outcomes to be of a moderate quality, using
      the GRADE approach due to small numbers and limited follow-up in the included
      studies. In addition, it was not possible to separate data for bulky early stage
      disease.In the one small trial that compared adjuvant chemotherapy followed by
      radiotherapy with adjuvant radiotherapy alone there was no difference in disease
      recurrence between the groups (one trial, 71 women; HR = 1.34; 95% CI 0.24 to
      7.66) and overall survival was not reported. We considered this evidence to be of
      a low quality.No trials compared adjuvant platinum-based chemotherapy with no
      adjuvant chemotherapy after surgery for early cervical cancer with risk factors
      for recurrence. AUTHORS' CONCLUSIONS: The addition of platinum-based chemotherapy
      to adjuvant radiotherapy (chemoradiation) may improve survival in women with
      early stage cervical cancer (IA2-IIA) and risk factors for recurrence. Adjuvant
      chemoradiation is associated with an increased risk of severe acute toxicity,
      although it is not clear whether this toxicity is significant in the long term
      due to a lack of long-term data. This evidence is limited by the small numbers
      and low to moderate methodological quality of the included studies. We await the
      results of three ongoing trials, which are likely to have an important impact on
      our confidence in this evidence.

PMID- 27873311
TI  - Corrigendum.

PMID- 27873310
TI  - Neonatal critical illness and development: white matter and hippocampus
      alterations in school-age neonatal extracorporeal membrane oxygenation survivors.
AB  - AIM: To examine the neurobiology of long-term neuropsychological deficits after
      neonatal extracorporeal membrane oxygenation (ECMO). METHOD: This cross-sectional
      study assessed white matter integrity and hippocampal volume of ECMO survivors (8
      15y) and healthy children (8-17y) using diffusion tensor imaging (DTI) and
      structural magnetic resonance imaging (MRI) respectively. Neuropsychological
      outcome was evaluated in ECMO survivors. Included clinical predictors of white
      matter integrity: age start ECMO, ECMO duration, highest oxygenation index before
      ECMO, highest mean airway pressure, and mechanical ventilation duration. RESULTS:
      ECMO survivors (n=23) had lower global fractional anisotropy than healthy
      children (n=54) (patients=0.368; comparison group=0.381; p=0.018), but similar
      global mean diffusivity (p=0.410). ECMO survivors had lower fractional anisotropy
      in the left cingulum bundle (ECMO survivors=0.345; comparison group=0.399;
      p<0.001) and higher mean diffusivity in a region of the left parahippocampal
      cingulum (patients=0.916; comparison group=0.871; p<0.001). Higher global mean
      diffusivity predicted worse verbal memory in ECMO survivors (n=17) (beta=-0.74,
      p=0.008). ECMO survivors (n=23) had smaller bilateral hippocampal volume than
      healthy children (n=43) (left, p<0.001; right, p<0.001) and this was related to
      worse verbal memory (left, beta=0.65, p=0.018; right, beta=0.71, p=0.006).
      INTERPRETATION: Neonatal ECMO survivors are at risk for long-term brain
      alterations, which may partly explain long-term neuropsychological impairments.
      Neuroimaging may contribute to better risk stratification of long-term
      impairments.

PMID- 27873313
TI  - Corrigendum.

PMID- 27873312
TI  - Nurturing clinical research globally to improve patient care.

PMID- 27873314
TI  - Characterisation of a novel cellobiose 2-epimerase from thermophilic
      Caldicellulosiruptor obsidiansis for lactulose production.
AB  - BACKGROUND: Lactulose, a bioactive lactose derivative, has been widely used in
      food and pharmaceutical industries. Isomerisation of lactose to lactulose by
      cellobiose 2-epimerase (CE) has recently attracted increasing attention, since CE
      produces lactulose with high yield from lactose as a single substrate. In this
      study, a new lactulose-producing CE from Caldicellulosiruptor obsidiansis was
      extensively characterised. RESULTS: The recombinant enzyme exhibited maximal
      activity at pH 7.5 and 70  degrees C. It displayed high thermostability with Tm
      of 86.7  degrees C. The half-life was calculated to be 8.1, 2.8 and 0.6 h at 75,
      80, and 85  degrees C, respectively. When lactose was used as substrate,
      epilactose was rapidly produced in a short period, and afterwards both epilactose
      and lactose were steadily isomerised to lactulose, with a final ratio of 35:11:54
      for lactose:epilactose:lactulose. When the reverse reaction was investigated
      using lactulose as substrate, both lactose and epilactose appeared to be steadily
      produced from the start. CONCLUSION: The recombinant CE showed both epimerisation
      and isomerisation activities against lactose, making it an alternative promising
      biocatalyst candidate for lactulose production. (c) 2016 Society of Chemical
      Industry.

PMID- 27873315
TI  - Incorporation of conjugated fatty acids into Nile tilapia (Oreochromis
      niloticus).
AB  - BACKGROUND: The aim of this work was to improve the nutritional quality of Nile
      tilapia meat through enriched diets with conjugated isomers of linolenic acid
      from tung oil. The transfer process of conjugated fatty acids (CFAs) into fish
      muscle tissue was evaluated by gas chromatography-flame ionization detection (GC
      FID) and easy ambient sonic-spray ionization mass spectrometry (EASI-MS).
      RESULTS: The results showed that conjugated fatty acids were transferred from
      enriched diet for muscle tissue of Nile tilapia. Conjugated linoleic acids
      biosynthesis from conjugated linolenic acids was also observed after 10 days.
      Other important fatty acids such as docosahexaenoic (DHA), eicosapentaenoic (EPA)
      and arachidonic (AA) acids were also identified over time; however, DHA showed
      the highest concentration when compared with EPA and AA compounds. CONCLUSION:
      Therefore, the nutritional quality of Nile tilapia was improved through feeding
      with enriched diets. The ingestion of these fish may contribute to reaching
      adequate levels of daily CFA consumption. Furthermore, other important substances
      which play an important role in human metabolism, such as EPA, DHA and AA, can
      also be ingested together with CFA. (c) 2016 Society of Chemical Industry.

PMID- 27873316
TI  - Aberrant gene expression with deficient apoptotic keratinocyte clearance may
      predispose to polymorphic light eruption.

PMID- 27873317
TI  - The B-cell-activating factor signalling pathway is associated with Helicobacter
      pylori independence in gastric mucosa-associated lymphoid tissue lymphoma without
      t(11;18)(q21;q21).
AB  - We previously reported that activation of the B-cell-activating factor (BAFF)
      pathway upregulates nuclear factor-kappaB (NF-kappaB) and induces BCL3 and BCL10
      nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse
      large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid
      tissue (MALT). However, the significance of BAFF expression in HP independence of
      gastric low-grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored.
      Sixty-four patients who underwent successful HP eradication for localized HP
      positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF
      expression was significantly higher in the HP-independent group than in the HP
      dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF
      receptor (BAFF-R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p <
      0.001), NF-kappaB (p65) (p = 0.001) and NF-kappaB (p52) (p = 0.005) expression
      were closely correlated with the HP independence of these tumours. Moreover, BAFF
      overexpression was significantly associated with BAFF-R expression and nuclear
      BCL3, BCL10, NF-kappaB (p65) and NF-kappaB (p52) expression. These findings were
      further validated in an independent cohort, including 40 HP-dependent cases and
      18 HP-independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The
      biological significance of BAFF signalling in t(11;18)(q21;q21)-negative lymphoma
      cells was further studied in two types of lymphoma B cell: OCI-Ly3 [non-germinal
      centre B-cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA-1
      [t(14;18)(q32;q21)/IGH-MALT1-positive DLBCL cell line]. In both cell lines, we
      found that BAFF activated the canonical NF-kappaB and AKT pathways, and induced
      the formation of BCL10-BCL3 complexes, which translocated to the nucleus. BCL10
      and BCL3 nuclear translocation and NF-kappaB (p65) transactivation were inhibited
      by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF
      also activated non-canonical NF-kappaB pathways (p52) through tumour necrosis
      factor receptor-associated factor 3 degradation, NF-kappaB-inducing kinase
      accumulation, inhibitor of kappaB kinase (IKK) alpha/beta phosphorylation and NF
      kappaB p100 processing in both cell lines. Our data indicate that the autocrine
      BAFF signal transduction pathway contributes to HP independence in gastric MALT
      lymphomas without the t(11;18)(q21;q21) translocation. Copyright (c) 2016
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 27873318
TI  - Tactic-specific benefits of polyandry in Chinook salmon Oncorhynchus tshawytscha.
AB  - This study examined whether polyandrous female Chinook salmon Oncorhynchus
      tshawytscha obtain benefits compared with monandrous females through an increase
      in hatching success. Both of the alternative reproductive tactics present in male
      O. tshawytscha (large hooknoses and small, precocious jacks) were used, such that
      eggs were either fertilized by a single male (from each tactic) or multiple males
      (using two males from the same or different tactics). The results show that
      fertilized eggs from the polyandrous treatments had a significantly higher
      hatching success than those from the monandrous treatments. It is also shown that
      sperm speed was positively related with offspring hatching success. Finally,
      there were tactic-specific effects on the benefits females received. The
      inclusion of jacks in any cross resulted in offspring with higher hatching
      success, with the cross that involved a male from each tactic providing offspring
      with the highest hatching success than any other cross. This study has important
      implications for the evolution of multiple mating and why it is so prevalent
      across taxa, while also providing knowledge on the evolution of mating systems,
      specifically those with alternative reproductive tactics.

PMID- 27873320
TI  - The behavioural homing response of adult chum salmon Oncorhynchus keta to amino
      acid profiles.
AB  - Adult chum salmon Oncorhynchus keta homing behaviour in a two-choice test tank (Y
      maze) was monitored using a passive integrated transponder (PIT)-tag system in
      response to river-specific dissolved free amino-acid (DFAA) profiles and revealed
      that the majority of O. keta showed a preference for artificial natal-stream
      water and tended to stay in this maze arm for a longer period; natal-stream water
      was chosen over a nearby tributary's water, but not when the O. keta were
      presented with a non-tributary water. The results demonstrate the ability of O.
      keta to discriminate artificial stream waters containing natural levels of DFAA.

PMID- 27873321
TI  - Life-history traits of the long-nosed skate Dipturus oxyrinchus.
AB  - This work investigates life-history traits of the long-nosed skate Dipturus
      oxyrinchus, which is a common by-catch in Sardinian waters. The reproductive
      variables were analysed from 979 specimens sampled during scientific and
      commercial hauls. Females (10.4-117.5 cm total length, LT ) attained larger sizes
      than males (14.5-99.5 cm LT ). To evaluate age and growth, a sub-sample of 130
      individuals (76 females and 54 males) were used. The age was estimated by annuli
      counts of sectioned vertebral centra. Four models were used for the length-at-age
      data: the von Bertalanffy, the exponential, the Gompertz and the logistic
      functions. According to the Akaike's information criterion, the Gompertz model
      seemed to provide the best fitting curve (Linfinity mean +/- s.e.: 127.55 +/-
      4.90 cm, k: 0.14 +/- 0.09, IP: 3.97 +/- 0.90 years). The oldest female and male
      were aged 17 (115.5 cm LT ) and 15 years (96.0 cm LT ), respectively. Lengths at
      maturity were 103.5 cm for females and 91.0 cm for males, corresponding to 90% of
      the maximum observed length in both sexes. The monthly distribution of maturity
      stages highlighted an extended reproductive cycle, with spawning females and
      active males being present almost throughout the year, as confirmed by the gonado
      somatic index. Ovarian fecundity reached a maximum of 26 yolked follicles with a
      mean +/- s.e. size of 19.7 +/- 6.5 mm.

PMID- 27873322
TI  - Non-medical prescribing versus medical prescribing for acute and chronic disease
      management in primary and secondary care.
AB  - BACKGROUND: A range of health workforce strategies are needed to address health
      service demands in low-, middle- and high-income countries. Non-medical
      prescribing involves nurses, pharmacists, allied health professionals, and
      physician assistants substituting for doctors in a prescribing role, and this is
      one approach to improve access to medicines. OBJECTIVES: To assess clinical,
      patient-reported, and resource use outcomes of non-medical prescribing for
      managing acute and chronic health conditions in primary and secondary care
      settings compared with medical prescribing (usual care). SEARCH METHODS: We
      searched databases including CENTRAL, MEDLINE, Embase, and five other databases
      on 19 July 2016. We also searched the grey literature and handsearched
      bibliographies of relevant papers and publications. SELECTION CRITERIA:
      Randomised controlled trials (RCTs), cluster-RCTs, controlled before-and-after
      (CBA) studies (with at least two intervention and two control sites) and
      interrupted time series analysis (with at least three observations before and
      after the intervention) comparing: 1. non-medical prescribing versus medical
      prescribing in acute care; 2. non-medical prescribing versus medical prescribing
      in chronic care; 3. non-medical prescribing versus medical prescribing in
      secondary care; 4 non-medical prescribing versus medical prescribing in primary
      care; 5. comparisons between different non-medical prescriber groups; and 6. non
      medical healthcare providers with formal prescribing training versus those
      without formal prescribing training. DATA COLLECTION AND ANALYSIS: We used
      standard methodological procedures expected by Cochrane. Two review authors
      independently reviewed studies for inclusion, extracted data, and assessed study
      quality with discrepancies resolved by discussion. Two review authors
      independently assessed risk of bias for the included studies according to EPOC
      criteria. We undertook meta-analyses using the fixed-effect model where studies
      were examining the same treatment effect and to account for small sample sizes.
      We compared outcomes to a random-effects model where clinical or statistical
      heterogeneity existed. MAIN RESULTS: We included 46 studies (37,337
      participants); non-medical prescribing was undertaken by nurses in 26 studies and
      pharmacists in 20 studies. In 45 studies non-medical prescribing as a component
      of care was compared with usual care medical prescribing. A further study
      compared nurse prescribing supported by guidelines with usual nurse prescribing
      care. No studies were found with non-medical prescribing being undertaken by
      other health professionals. The education requirement for non-medical prescribing
      varied with country and location.A meta-analysis of surrogate markers of chronic
      disease (systolic blood pressure, glycated haemoglobin, and low-density
      lipoprotein) showed positive intervention group effects. There was a moderate
      certainty of evidence for studies of blood pressure at 12 months (mean difference
      (MD) -5.31 mmHg, 95% confidence interval (CI) -6.46 to -4.16; 12 studies, 4229
      participants) and low-density lipoprotein (MD -0.21, 95% CI -0.29 to -0.14; 7
      studies, 1469 participants); we downgraded the certainty of evidence from high
      due to considerations of serious inconsistency (considerable heterogeneity),
      multifaceted interventions, and variable prescribing autonomy. A high-certainty
      of evidence existed for comparative studies of glycated haemoglobin management at
      12 months (MD -0.62, 95% CI -0.85 to -0.38; 6 studies, 775 participants). While
      there appeared little difference in medication adherence across studies, a meta
      analysis of continuous outcome data from four studies showed an effect favouring
      patient adherence in the non-medical prescribing group (MD 0.15, 95% CI 0.00 to
      0.30; 4 studies, 700 participants). We downgraded the certainty of evidence for
      adherence to moderate due to the serious risk of performance bias. While little
      difference was seen in patient-related adverse events between treatment groups,
      we downgraded the certainty of evidence to low due to indirectness, as the range
      of adverse events may not be related to the intervention and selective reporting
      failed to adequately report adverse events in many studies.Patients were
      generally satisfied with non-medical prescriber care (14 studies, 7514
      participants). We downgraded the certainty of evidence from high to moderate due
      to indirectness, in that satisfaction with the prescribing component of care was
      only addressed in one study, and there was variability of satisfaction measures
      with little use of validated tools. A meta-analysis of health-related quality of
      life scores (SF-12 and SF-36) found a difference favouring usual care for the
      physical component score (MD 1.17, 95% CI 0.16 to 2.17), but not the mental
      component score (MD 0.58, 95% CI -0.40 to 1.55). However, the quality of life
      measurement may more appropriately reflect composite care rather than the
      prescribing component of care, and for this reason we downgraded the certainty of
      evidence to moderate due to indirectness of the measure of effect. A wide variety
      of resource use measures were reported across studies with little difference
      between groups for hospitalisations, emergency department visits, and outpatient
      visits. In the majority of studies reporting medication use, non-medical
      prescribers prescribed more drugs, intensified drug doses, and used a greater
      variety of drugs compared to usual care medical prescribers.The risk of bias
      across studies was generally low for selection bias (random sequence generation),
      detection bias (blinding of outcome assessment), attrition bias (incomplete
      outcome data), and reporting bias (selective reporting). There was an unclear
      risk of selection bias (allocation concealment) and for other biases. A high risk
      of performance bias (blinding of participants and personnel) existed. AUTHORS'
      CONCLUSIONS: The findings suggest that non-medical prescribers, practising with
      varying but high levels of prescribing autonomy, in a range of settings, were as
      effective as usual care medical prescribers. Non-medical prescribers can deliver
      comparable outcomes for systolic blood pressure, glycated haemoglobin, low
      density lipoprotein, medication adherence, patient satisfaction, and health
      related quality of life. It was difficult to determine the impact of non-medical
      prescribing compared to medical prescribing for adverse events and resource use
      outcomes due to the inconsistency and variability in reporting across studies.
      Future efforts should be directed towards more rigorous studies that can clearly
      identify the clinical, patient-reported, resource use, and economic outcomes of
      non-medical prescribing, in both high-income and low-income countries.

PMID- 27873319
TI  - Lung neuroendocrine tumours: deep sequencing of the four World Health
      Organization histotypes reveals chromatin-remodelling genes as major players and
      a prognostic role for TERT, RB1, MEN1 and KMT2D.
AB  - Next-generation sequencing (NGS) was applied to 148 lung neuroendocrine tumours
      (LNETs) comprising the four World Health Organization classification categories:
      53 typical carcinoid (TCs), 35 atypical carcinoid (ACs), 27 large-cell
      neuroendocrine carcinomas, and 33 small-cell lung carcinomas. A discovery screen
      was conducted on 46 samples by the use of whole-exome sequencing and high
      coverage targeted sequencing of 418 genes. Eighty-eight recurrently mutated genes
      from both the discovery screen and current literature were verified in the 46
      cases of the discovery screen, and validated on additional 102 LNETs by targeted
      NGS; their prevalence was then evaluated on the whole series. Thirteen of these
      88 genes were also evaluated for copy number alterations (CNAs). Carcinoids and
      carcinomas shared most of the altered genes but with different prevalence rates.
      When mutations and copy number changes were combined, MEN1 alterations were
      almost exclusive to carcinoids, whereas alterations of TP53 and RB1 cell cycle
      regulation genes and PI3K/AKT/mTOR pathway genes were significantly enriched in
      carcinomas. Conversely, mutations in chromatin-remodelling genes, including those
      encoding histone modifiers and members of SWI-SNF complexes, were found at
      similar rates in carcinoids (45.5%) and carcinomas (55.0%), suggesting a major
      role in LNET pathogenesis. One AC and one TC showed a hypermutated profile
      associated with a POLQ damaging mutation. There were fewer CNAs in carcinoids
      than in carcinomas; however ACs showed a hybrid pattern, whereby gains of TERT,
      SDHA, RICTOR, PIK3CA, MYCL and SRC were found at rates similar to those in
      carcinomas, whereas the MEN1 loss rate mirrored that of TCs. Multivariate
      survival analysis revealed RB1 mutation (p = 0.0005) and TERT copy gain (p =
      0.016) as independent predictors of poorer prognosis. MEN1 mutation was
      associated with poor prognosis in AC (p = 0.0045), whereas KMT2D mutation
      correlated with longer survival in SCLC (p = 0.0022). In conclusion, molecular
      profiling may complement histology for better diagnostic definition and
      prognostic stratification of LNETs. (c) 2016 The Authors. The Journal of
      Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of
      Great Britain and Ireland.

PMID- 27873323
TI  - Inflammation enhances the vaccination potential of CD40-activated B cells in
      mice.
AB  - Vaccination with antigen-pulsed CD40-activated B (CD40-B) cells can efficiently
      lead to the in vivo differentiation of naive CD8+ T cells into fully functional
      effectors. In contrast to bone marrow-derived dendritic cell (BMDC) vaccination,
      CD40-B cell priming does not allow for memory CD8+ T-cell generation but the
      reason for this deficiency is unknown. Here, we show that compared to BMDCs,
      murine CD40-B cells induce lower expression of several genes regulated by T-cell
      receptor signaling, costimulation, and inflammation (signals 1-3) in mouse T
      cells. The reduced provision of signals 1 and 2 by CD40-B cells can be explained
      by a reduction in the quality and duration of the interactions with naive CD8+ T
      cells as compared to BMDCs. Furthermore, CD40-B cells produce less inflammatory
      mediators, such as IL-12 and type I interferon, and increasing inflammation by
      coadministration of polyriboinosinic-polyribocytidylic acid with CD40-B-cell
      immunization allowed for the generation of long-lived and functional CD8+ memory
      T cells. In conclusion, it is possible to manipulate CD40-B-cell vaccination to
      promote the formation of long-lived functional CD8+ memory T cells, a key step
      before translating the use of CD40-B cells for therapeutic vaccination.

PMID- 27873324
TI  - Red blood cell alloimmunization in patients with sickle cell disease: correlation
      with HLA and cytokine gene polymorphisms.
AB  - BACKGROUND: The reason for the difference in susceptibility to red blood cell
      (RBC) alloimmunization among patients with sickle cell disease (SCD) is not
      clearly understood and is probably the result of multiple factors. Our hypothesis
      is that genetic polymorphisms are associated with RBC alloimmunization. STUDY
      DESIGN AND METHODS: We investigated the possible association of susceptibility to
      RBC alloimmunization with polymorphisms of HLA and cytokines genes in 161 SCD
      patients prior exposed to RBC transfusion. Cytokine gene polymorphisms were
      analyzed by polymerase chain reaction (PCR) and TaqMan assays. HLA Class I
      genotyping was performed using PCR-specific sequence of oligonucleotides.
      Polymorphism frequencies were compared using the Fisher's exact test. RESULTS:
      Our results revealed increased percentage of the A allele and the GA genotype of
      the TNFA -308G/A cytokine among alloimmunized patients when compared to
      nonalloimmunized patients (A allele, 16.4% vs. 6.8%, p = 0.004; GA genotype,
      32.8% vs. 11.7%, p = 0.0021). In addition, the IL1B -511T allele and the IL1B 
      511TT and CT genotype frequencies were overrepresented among alloimmunized
      patients (T allele, 53.0% vs. 37.5%, p = 0.0085; CT + TT genotypes, 81.82% vs.
      60.87%, p = 0.0071). In relation to HLA Class I, we found a higher frequency of
      HLA-DRB1*15 among patients alloimmunized to Rh antigens when compared to
      nonalloimmunized patients (15.63% vs. 6.98%, p = 0.044). CONCLUSION: Brazilian
      SCD patients with the TNFA, IL1B, and HLA-DRB1 gene polymorphisms were at
      increased risk of becoming alloimmunized by RBC transfusions. These findings may
      contribute to the development of future therapeutic strategies for patients with
      SCD with higher susceptibility of alloimmunization.

PMID- 27873326
TI  - Complications of turbinate reduction surgery in combination with tonsillectomy in
      pediatric patients.
AB  - OBJECTIVES/HYPOTHESIS: To examine whether the addition of turbinoplasty to
      tonsillectomy and adenoidectomy (T&A) increases the risk of postoperative
      complications. STUDY DESIGN: Retrospective cohort study of children (18 years old
      and younger) who underwent tonsillectomy and/or turbinoplasty between July 1,
      2013 and June 30, 2015 using the 2016 Pediatric Health Information System
      administrative database METHODS: Patients were divided into three groups: 1) T&A
      and turbinoplasty, 2) T&A alone, and 3) turbinoplasty alone. Postoperative
      revisit, hemorrhage requiring cautery, and blood transfusion rates were compared
      between groups. RESULTS: A total of 75,761 patients met inclusion criteria: 3,079
      underwent both T&A and turbinoplasty, 72,043 underwent T&A alone, and 639
      underwent turbinoplasty alone. The rate of 14-day relevant revisits after T&A in
      combination with turbinate reduction surgery was not significantly higher than
      that of T&A alone (9.4% vs. 8.6%; P = .11). The revisit rate after turbinoplasty
      alone was 1.4%. Indications for revisits did not differ between the T&A and
      turbinoplasty group versus T&A alone group (P = .23). Furthermore, the rates of
      hemorrhage requiring cauterization was similar between the two groups (1.4% vs.
      1.5%; P = .64). Twenty-one patients who underwent T&A alone required blood
      transfusion after they were readmitted; no cases in the other two groups required
      blood transfusion. CONCLUSIONS: Turbinoplasty and T&A performed together do not
      increase the risk of postoperative revisit or hemorrhage requiring cauterization,
      and can therefore be considered as a combined procedure. Pediatric patients will
      benefit from avoiding the additional risk of multiple anesthetics and repeated
      intubation. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1920-1923, 2017.

PMID- 27873325
TI  - Dynamic nanomechanical analysis of the vocal fold structure in excised larynges.
AB  - OBJECTIVES/HYPOTHESIS: Quantification of clinical outcomes after vocal fold (VF)
      interventions is challenging with current technology. High-speed digital imaging
      and optical coherence tomography (OCT) of excised larynges assess intact
      laryngeal function, but do not provide critical biomechanical information. We
      developed a protocol to quantify tissue properties in intact, excised VFs using
      dynamic nanomechanical analysis (nano-DMA) to obtain precise biomechanical
      properties in the micrometer scale. STUDY DESIGN: Experimental animal study.
      METHODS: Three pig larynges were bisected in the sagittal plane, maintaining an
      intact anterior commissure, and subjected to nano-DMA at nine locations with a
      250-MUm flat-tip punch and frequency sweep load profile (10-105 Hz, 1,000 MUN
      peak force) across the free edge of the VF and inferiorly along the conus
      elasticus. RESULTS: Storage, loss, and complex moduli increased inferiorly from
      the free edge. Storage moduli increased from a mean of 32.3 kPa (range, 6.5-55.38
      kPa) at the free edge to 46.3kPa (range, 7.4-71.6) 5 mm below the free edge, and
      71.4 kPa (range, 33.7-112 kPa) 1 cm below the free edge. Comparable values were
      11.6 kPa (range, 5.0-20.0 kPa), 16.7 kPa (range, 5.7-26.8 kPa), and 22.6 kPa
      (range, 9.7-38.0 kPa) for loss modulus, and 35.7 kPa (range, 14.4-56.4 kPa), 50.1
      kPa (range, 18.7-72.8 kPa), and 75.4 kPa (range, 42.0-116.0 kPa) for complex
      modulus. Another larynx repeatedly frozen and thawed during technique development
      had similarly increased storage, loss, and complex modulus trends across
      locations. CONCLUSIONS: Nano-DMA of the intact hemilarynx provides a platform for
      quantification of biomechanical responses to a myriad of therapeutic
      interventions to complement data from high-speed imaging and OCT. LEVEL OF
      EVIDENCE: NA Laryngoscope, 127:E225-E230, 2017.

PMID- 27873328
TI  - Liposome-Encapsulated Hemoglobin Improves Tumor Oxygenation as Detected by Near
      Infrared Spectroscopy in Colon Carcinoma in Mice.
AB  - Liposome-encapsulated hemoglobin (LEH) with high (h-LEH, P50 O2  = 10 mm Hg) or
      low O2 affinity (l-LEH, P50 O2  = 40 mm Hg) may improve O2 delivery to sensitize
      tumor tissues for radiotherapy. A total of 10 mL/kg of h-LEH, l-LEH, red blood
      cells (RBCs), or saline was infused in mice transplanted with murine colon
      carcinoma with near-infrared spectroscopy (NIRS) detectors set at the tumor
      (right leg) and intact muscle (left leg). NIRS recorded changes in the amount of
      oxyhemoglobin (oxyHb), deoxyhemoglobin (deoxyHb), and their sum (tHb) with the
      animals spontaneously breathing room air (10 min), pure O2 (5 min), and then back
      to room air. The tumor was finally excised for histological examination. In mice
      treated with h-LEH, tHb significantly increased compared to mice receiving other
      solutions. The magnitude was significantly attenuated in the tumor compared to
      the intact muscle under room air. Reciprocal changes in oxyHb and deoxyHb between
      intact muscle and tumor in response to infused solutions allowed assumption of
      average tissue PO2 between 30 and 40 mm Hg in muscle and at around 10 mm Hg in
      tumor. While O2 respiration increased oxyHb and decreased deoxyHb both in muscle
      and tumor, their sum or tHb consistently decreased in muscle and increased in
      tumor regardless of preceding infusion. Such responses were totally reversed when
      mice were placed under hypoxia (10% O2 ), suggesting that a lack of physiological
      circulatory regulation in tumor may account for heavier immunohistochemical
      staining for human hemoglobin in tumors of mice treated with h-LEH than with l
      LEH. The results suggest that h-LEH may cause significant tumor oxygenation
      compared to RBC, l-LEH, or saline probably due to its nanometer size (vs. RBC)
      and high O2 affinity (vs. l-LEH) without increasing O2 content in the intact
      tissue (vs. O2 respiration) probably due to a lack of physiological circulatory
      regulation.

PMID- 27873327
TI  - Cost-effectiveness of transfacial gland-preserving removal of parotid sialoliths.
AB  - OBJECTIVE: Examine outcomes of transfacial gland-preserving removal of difficult
      parotid stones and compare the cost and operative time to traditional
      parotidectomy. STUDY DESIGN: Cost-effectiveness analysis and retrospective chart
      review. METHODS: Patients who underwent transfacial removal of symptomatic
      parotid sialoliths at a tertiary medical center from June 2010 to July 2015 were
      evaluated. Outcomes included operative technique, stone size, stone location,
      complications, and symptom relief. In addition, patients who underwent
      traditional parotidectomy for chronic sialadenitis were identified. The charges
      and times for both procedures were reviewed and compared. RESULTS: Forty-four
      patients underwent transfacial resection for symptomatic parotid sialolithiasis.
      Stones were most often located in the main duct and hilum (53.3%), with fewer
      intraglandular stones (46.7%). No facial nerve weakness was observed. Of those
      with follow-up, 33 (87%) patients reported at least partial resolution of
      symptoms. Overall transfacial technique charges were significantly less expensive
      (U.S.$) than parotidectomy (mean difference -8,064.09; 95% confidence interval
      [CI] -13,472.78 to -2,655.40; P = 0.033). Anesthesia charges (mean difference 
      2,997.85; 95% CI, -5,748.81 to -246.89; P = 0.035) and operating room charges
      (mean difference -4,793.91; 95% CI, -8,958.09 to -629.72; P = 0.028) were also
      less expensive for the transfacial technique. Finally, mean procedure time for
      transfacial removal of parotid stones was shorter than for parotidectomy (120.2
      +/- 49.9 vs. 178.4 +/- 41.3 minutes, respectively; P = 0.002). CONCLUSION:
      Transfacial gland-preserving removal of difficult parotid stones is a well
      tolerated and effective alternative to parotidectomy. Moreover, it is faster and
      less expensive than parotidectomy, maximizing both surgeon time and hospital
      resources. LEVEL OF EVIDENCE: 4. Laryngoscope, 127:1080-1086, 2017.

PMID- 27873329
TI  - One-step zymogram method for the simultaneous detection of cellulase/xylanase
      activity and molecular weight estimation of the enzyme.
AB  - Here, we describe a zymographic method for the simultaneous detection of
      enzymatic activity and molecular weight (MW) estimation, following a single
      electrophoresis step. This involved separating cellulase and xylanase activities
      from bacteria and fungi, obtained from different sources, such as commercial
      extracts, crude extract and purified proteins, under denaturing conditions, by
      10% polyacrylamide gel electrophoresis, using polyacrylamide gels copolymerized
      with 1% (w/v) carboxymethylcellulose or beechwood xylan as substrates. Then,
      enzymes were refolded by treatment with 2.5% Triton X-100 in an appropriate
      buffer for each enzymatic activity, and visualized by Coomassie blue staining for
      MW estimation. Finally, Congo red staining revealed bio-active cellulase and
      xylanase bands after electrophoretic separation of the proteins in the
      preparations. This method may provide a useful additional tool for screening of
      particular cellulase and xylanase producers, identification and MW estimation of
      polypeptides that manifest these activities, and for monitoring and control of
      fungal and bacterial cellulase and xylanase production.

PMID- 27873330
TI  - The burden of nonadherence among adults with asthma: a role for shared decision
      making.
AB  - A shared approach to decision-making framework has been suggested for chronic
      disease management especially where multiple treatment options exist. Shared
      decision-making (SDM) requires that both physician and patients are actively
      engaged in the decision-making process, including information exchange;
      expressing treatment preferences; as well as agreement over the final treatment
      decision. Although SDM appears well supported by patients, practitioners and
      policymakers alike, the current challenge is to determine how best to make SDM a
      reality in everyday clinical practice. Within the context of asthma, adherence
      rates are poor and are linked to outcomes such as reduced asthma control,
      increased symptoms, healthcare expenditures, and lower patient quality of life.
      It has been suggested that SDM can improve treatment adherence and that ignoring
      patients' personal goals and preferences may result in reduced rates of
      adherence. Furthermore, understanding predictors of poor treatment adherence is a
      necessary step toward developing effective strategies to improve the patient
      reported and clinically important outcomes. Here, we describe why a shared
      approach to treatment decision-making for asthma has the potential to be an
      effective tool for improving adherence, with associated clinical and patient
      related outcomes. In addition, we explore insights into the reasons why SDM has
      not been implemented into routine clinical practice.

PMID- 27873331
TI  - Low Tidal Volume Reduces Lung Inflammation Induced by Liquid Ventilation in
      Piglets With Severe Lung Injury.
AB  - Total liquid ventilation (TLV) is an alternative treatment for severe lung
      injury. High tidal volume is usually required for TLV to maintain adequate CO2
      clearance. However, high tidal volume may cause alveolar barotrauma. We aim to
      investigate the effect of low tidal volume on pulmonary inflammation in piglets
      with lung injury and under TLV. After the establishment of acute lung injury
      model by infusing lipopolysaccharide, 12 piglets were randomly divided into two
      groups, TLV with high tidal volume (25 mL/kg) or with low tidal volume (6 mL/kg)
      for 240 min, respectively. Extracorporeal CO2 removal was applied in low tidal
      volume group to improve CO2 clearance and in high tidal volume group as sham
      control. Gas exchange and hemodynamic status were monitored every 30 min during
      TLV. At the end of the study, pulmonary mRNA expression and plasmatic
      concentration of interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured by
      collecting lung tissue and blood samples from piglets. Arterial blood pressure,
      PaO2 , and PaCO2 showed no remarkable difference between groups during the
      observation period. Compared with high tidal volume strategy, low tidal volume
      resulted in 76% reduction of minute volume and over 80% reduction in peak
      inspiratory pressure during TLV. In addition, low tidal volume significantly
      diminished pulmonary mRNA expression and plasmatic level of IL-6 and IL-8. We
      conclude that during TLV, low tidal volume reduces lung inflammation in piglets
      with acute lung injury without compromising gas exchange.

PMID- 27873332
TI  - Monitoring of compositional changes during berry ripening in grape seed extracts
      of cv. Sangiovese (Vitis vinifera L.).
AB  - BACKGROUND: Seed oil and flours have been attracting the interest of researchers
      and industry, since they contain various bioactive components. We monitored the
      effects of ripening on lipids, monomeric flavan-3-ols, proanthocyanidins and
      tocols concentration in seed extracts from organically cultivated cv. Sangiovese
      vines. RESULTS: Linoleic acid was the most abundant fatty acid, followed by
      oleic, palmitic and stearic acids. The tocols detected were alpha-tocopherol,
      alpha-tocotrienol and gamma-tocotrienol. The proanthocyanidins degree of
      polymerisation ranged from dimers to dodecamers; moreover, monomeric flavan-3-ols
      and polymeric proanthocyanidins were detected. Total flavan-3-ols (monomers,
      oligomers and polymers) concentration in grape seeds decreased during ripening.
      CONCLUSIONS: Fatty acids reached the highest level in post-veraison. The
      concentration of these compounds varied considerably during ripening. Capric acid
      has been found for the first time in grape seeds. alpha-Tocopherol and gamma
      tocotrienol decreased during ripening, while alpha-tocotrienol increased. The
      HPLC analysis with fluorimetric detection, conducted for the first time on cv.
      Sangiovese, revealed that the concentration of flavan-3-ols monomers, oligomeric
      proanthocyanidins and polymers greatly changed during ripening. These results
      suggest that the timing of bunch harvest plays a crucial role in the valorisation
      of grape seed flour. (c) 2016 Society of Chemical Industry.

PMID- 27873333
TI  - Simulating survival data with predefined censoring rates for proportional hazards
      models.
AB  - The proportional hazard model is one of the most important statistical models
      used in medical research involving time-to-event data. Simulation studies are
      routinely used to evaluate the performance and properties of the model and other
      alternative statistical models for time-to-event outcomes under a variety of
      situations. Complex simulations that examine multiple situations with different
      censoring rates demand approaches that can accommodate this variety. In this
      paper, we propose a general framework for simulating right-censored survival data
      for proportional hazards models by simultaneously incorporating a baseline hazard
      function from a known survival distribution, a known censoring time distribution,
      and a set of baseline covariates. Specifically, we present scenarios in which
      time to event is generated from exponential or Weibull distributions and
      censoring time has a uniform or Weibull distribution. The proposed framework
      incorporates any combination of covariate distributions. We describe the steps
      involved in nested numerical integration and using a root-finding algorithm to
      choose the censoring parameter that achieves predefined censoring rates in
      simulated survival data. We conducted simulation studies to assess the
      performance of the proposed framework. We demonstrated the application of the new
      framework in a comprehensively designed simulation study. We investigated the
      effect of censoring rate on potential bias in estimating the conditional
      treatment effect using the proportional hazard model in the presence of
      unmeasured confounding variables. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27873334
TI  - Rapid allergen-induced interleukin-17 and interferon-gamma secretion by skin
      resident memory CD8+ T cells.
AB  - BACKGROUND: Skin-resident memory T (TRM ) cells are associated with immunological
      memory in the skin. Whether immunological memory responses to allergens in the
      skin are solely localized to previously allergen-exposed sites or are present
      globally in the skin is not clear. Furthermore, the mechanisms whereby TRM cells
      induce rapid recall responses need further investigation. OBJECTIVES: To study
      whether contact allergens induce local and/or global memory, and to determine the
      mechanisms involved in memory responses in the skin. METHODS: To address these
      questions, we analysed responses to contact allergens in mice and humans
      sensitized to 2,4-dinitrofluorobenzene and nickel, respectively. RESULTS:
      Challenge responses in both mice and humans were dramatically increased at sites
      previously exposed to allergens as compared with previously unexposed sites.
      Importantly, the magnitude of the challenge response correlated with the
      epidermal accumulation of interleukin (IL)-17A-producing and interferon (IFN)
      gamma-producing TRM cells. Moreover, IL-17A and IFN-gamma enhanced allergen
      induced IL-1beta production in keratinocytes. CONCLUSIONS: We show that
      sensitization with contact allergens induces a strong, long-lasting local memory
      and a weaker, temporary global immunological memory response to the allergen that
      is mediated by IL-17A-producing and IFN-gamma-producing CD8+ TRM cells.

PMID- 27873335
TI  - Lip b 1 is a novel allergenic protein isolated from the booklouse, Liposcelis
      bostrychophila.
AB  - BACKGROUND: Booklice, belonging to the order Psocoptera, are small household
      insect pests that are distributed worldwide. Liposcelis bostrychophila, a common
      home-inhabiting species of booklouse, infests old books, sheets of paper, and
      stored food. Recent entomological and serological studies demonstrated that L.
      bostrychophila accounted for the majority of detectable insects in house dust and
      could be a potent inducer of respiratory allergy. Our recent proteomic analysis
      identified a potent allergenic protein from L. bostrychophila, designated Lip b
      1, and determined its partial amino acid sequences. METHODS: Cloning of cDNAs for
      Lip b 1 was performed by large-scale transcriptome analysis (RNA-seq) and
      subsequent reverse transcription polymerase chain reaction. The full-length amino
      acid sequences deduced from Lip b 1 cDNAs were bioinformatically analyzed. The
      recombinant proteins of glutathione S-transferase (GST)-fused Lip b 1 were
      analyzed by Western blot and enzyme-linked immunosorbent assay. RESULTS: Lip b 1
      cDNAs encoding two types of 254-amino acid proteins were cloned. The clones
      shared 87% identity, and the deduced molecular weights and isoelectric points
      were consistent with those determined in our previous study. The two types of Lip
      b 1 proteins in the GST-fused form were similarly reactive with sera from
      allergic patients sensitized with L. bostrychophila. CONCLUSIONS: Lip b 1 is a
      novel protein possibly causing booklouse allergy.

PMID- 27873337
TI  - Age-related common miRNA polymorphism associated with severe toxicity in lung
      cancer patients treated with platinum-based chemotherapy.
AB  - Platinum-based chemotherapy toxicity severely impedes successful treatment in
      lung cancer patients. MicroRNAs (miRs) have a significant impact on the
      occurrence and survival rate of lung cancer. The purpose of this study was to
      investigate the association between common miRNA variants and platinum-based
      chemotherapy toxicity in lung cancer patients. A total of eight functional single
      nucleotide polymorphisms (SNPs) of miRNA were genotyped in 408 lung cancer
      patients by MALDI-TOF mass spectrometry. All the patients were histologically
      confirmed as lung cancer, and were treated with platinum-based chemotherapy for
      at least two cycles. It was found that the polymorphism rs2042553 of miR-5197 had
      a significant association with overall severe toxicity in both additive (P=.031,
      odds ratio [OR]=1.41, 95% confidence interval [CI] 1.03-1.93) and dominant
      (P=.009, OR=1.80, 95% CI 1.16-2.80) models. MiR-605 rs2043556 was significantly
      related to severe hepatotoxicity in dominant model (P=.022, OR=2.51, 95% CI 1.12
      4.14). In addition, rs2910164 of miR-146a had marginal statistical effect on
      severe hepatotoxicity in additive model (P=.054). The subgroup analyses showed
      that miR-27a rs895819 was related to gastrointestinal toxicity in age >56 years
      old, smoking and non-smoking patients. Taken together, our results revealed that
      polymorphisms of miR-5197, miR-605, miR-146a, and miR-27a contributed to the
      chemotherapy toxicity of lung cancer, which may serve as a predictive tool for
      toxicity evaluation of platinum-based chemotherapy in lung cancer patients.

PMID- 27873336
TI  - A Comparison of Two Surgical Techniques for the Second Stage of Brachiobasilic
      Arteriovenous Fistula Creation.
AB  - Two-stage transposed brachiobasilic arteriovenous fistula is a common procedure
      after brachiobasilic fistula (BBF) creation. Different techniques can be used for
      basilic vein transposition but few comparative literature reports are available.
      The aim of our study was to compare two different techniques for basilic vein
      transposition. The first maintains the BBF anastomosis and the basilic vein is
      placed in a subcutaneous pocket (BBAVF). The second transects the basilic vein at
      the BBF anastomosis and tunnels it superficially, with a new BBF in the brachial
      artery (BBAVFTn). From 2009 to 2014, all patients who underwent basilic vein
      superficialization were treated by one of the two techniques, recorded in a
      dedicated database and retrospectively reviewed. The surgeon chose the technique
      on the basis of personal preference. The two techniques were compared in terms of
      perioperative complications, length of hospital stay, time of cannulation, ease
      of cannulation, and long-term patency. Eighty patients were included in the
      study: 40 (50%) BBAVF and 40 (50%) BBAVFTn. Length of hospital stay was similar
      in the two groups (median [interquartile range-IQR] 3(2) [BBAVF] vs. 2(1)
      [BBAVFTn], P = 0.52, respectively). BBAVFTn was associated with a lower hematoma
      incidence (1/40 [2.5%] vs. 15/40 [37.5%], P = 0.01), shorter first cannulation
      time (median IQR: 11(10) vs. 23(8) days, P = 0.01) and easier cannulation
      compared with BBAVF (32/40 [80%] vs. 15/40 [37.5%], P < 0.001). Median (IQR)
      follow-up was 16(7) months. No statistical differences in terms of primary and
      assisted primary patency were found in BBAVFTn vs. BBAVF (at 24 months 91(5) vs.
      71(7), P = 0.21 and 93(6) vs. 78(8), P = 0.33, respectively). Patients who
      underwent BBAVFTn surgery showed fewer surgical complications, better dialytic
      performance, and easier cannulation compared with those submitted to BBAVF.

PMID- 27873338
TI  - High myopes have lower normalised corneal tangent moduli (less 'stiff' corneas)
      than low myopes.
AB  - PURPOSE: To compare corneal tangent moduli between low and high myopes. METHODS:
      Corneal hysteresis (CH) and corneal resistance factor (CRF) of 32 low and 32 high
      myopes were obtained using an Ocular Response Analyzer, followed by a corneal
      indentation device that measured corneal stiffness. Corneal topography,
      pachymetry, Goldmann applanation tonometry intraocular pressure (GAT-IOP), and
      corneal compensated intraocular pressure (IOPcc) were also obtained. Corneal
      tangent modulus was calculated on the basis of corneal stiffness, central corneal
      thickness and corneal radius. Comparisons between groups and associations between
      corneal biomechanical and ocular parameters were performed. RESULTS: Corneal
      tangent moduli were positively correlated with GAT-IOP (R2 = 0.078, p = 0.025),
      and IOPcc (R2 = 0.12, p = 0.006). Despite similarity in corneal thickness and
      radius, high myopes exhibited a significantly higher IOPcc (16.4 +/- 2.51 mmHg)
      than low myopes (13.1 +/- 1.96 mmHg; t(62) = -5.57, p < 0.0001). Both groups had
      similar corneal stiffness (0.063 +/- 0.0085 and 0.063 +/- 0.0079 N mm-1 for low
      and high myopes, respectively) and CRF (9.6 +/- 1.58 and 9.5 +/- 1.90 mmHg for
      low and high myopes, respectively). Moreover, high myopes exhibited a
      significantly lower CH (9.5 +/- 1.51 mmHg) than low myopes (10.6 +/- 1.38 mmHg;
      t(62) = 2.92, p = 0.005). After normalising corneal tangent moduli to the mean
      intraocular pressure in normal eyes (15.5 mmHg) using IOPcc, high myopes showed a
      significantly lower corneal tangent moduli (0.47 +/- 0.087 MPa) than low myopes
      (0.57 +/- 0.099 MPa; t(62) = 4.17, p < 0.0001). CONCLUSIONS: High myopes had
      lower normalised corneal tangent moduli than low myopes, which indicated that
      their corneas were less stiff. This is the first in vivo study comparing elastic
      moduli of the cornea in different refractive groups. Further studies are
      warranted to understand whether a less stiff cornea is a cause for or an outcome
      from myopia development.

PMID- 27873339
TI  - Consequences of an Extended Recruitment on Participation in the Follow-Up of a
      Child Study: Results from the German IDEFICS Cohort.
AB  - BACKGROUND: Declining response proportions in population-based studies are often
      countered by extended recruitment efforts at baseline that may, however, result
      in higher attrition in a subsequent follow-up. This study analysed the effect of
      extended recruitment efforts on attrition at the first follow-up of a child
      cohort. METHODS: We used paradata (i.e. information about the process of data
      collection) from the German IDEFICS cohort investigating dietary- and life style
      induced health effects on children to quantify recruitment effort and classify
      respondents as completing the recruitment early vs. late for baseline and follow
      up separately. Multilevel logistic regression models were used to investigate the
      association between recruitment effort and attrition at follow-up (loss to follow
      up) adjusted for sociodemographic and health related variables. RESULTS:
      Individuals who were late respondents at baseline and early respondents at the
      follow-up had a higher chance of attrition (odds ratio 1.65, 95% confidence
      interval (CI) 1.19, 2.28) as compared to other groups. An investigation of
      reasons for non-participation revealed that members of this group were more
      likely to be not reachable by phone. CONCLUSIONS: An extended recruitment effort
      at baseline of a child cohort study is not per se associated with a higher chance
      of attrition at follow-up. Much care should be taken to collect valid telephone
      numbers.

PMID- 27873340
TI  - Adequacy of physician documentation and correlation with assessment of
      transfusion appropriateness: a follow-up study in the setting of prospective
      audits and patient blood management.
AB  - BACKGROUND: A previous study in our hospitals correlated suboptimal documentation
      and failure to justify transfusions. In light of implemented blood-conservation
      strategies, including patient blood management (PBM) and prospective audits
      (PAs), we performed a follow-up study. STUDY DESIGN AND METHODS: We reviewed
      prospectively audited red blood cell (RBC) transfusions received by adult
      patients from January to July 2014. Survey forms were used to assess the level of
      documentation and to classify documentation as adequate, intermediate, or
      inadequate. Transfusions were deemed justified or not by comparisons with
      hospital transfusion guidelines. We also analyzed the effect of implemented blood
      conservation strategies on our hospital transfusion rates and costs from 2009 to
      2015. RESULTS: During the study period, there were 259 prospectively audited
      transfusion events (TEs) (one or more RBC units transfused to a patient), of
      which we reviewed 94 TEs (36.3%) in 87 patients. TEs with suboptimal
      (intermediate and inadequate) documentation accounted for 46.8% of the reviewed
      TEs, of which 81.8% could not be justified compared with 18.0% of nonjustified,
      adequately documented TEs. The correlation between suboptimal documentation and
      failure to justify transfusion was significant (p < 0.001). This correlation
      remained even in a comparison between the site with a PBM program and the sites
      without such a program. Overall transfusion rates declined after the introduction
      of PA, although the decline was only statistically significant at the sites with
      a PBM program. CONCLUSION: Suboptimal transfusion documentation remains
      problematic and is highly correlated with nonjustifiable transfusions. Newly
      adopted approaches to minimize blood transfusions have not improved transfusion
      documentation and corresponding out-of-guideline transfusions, although overall
      transfusions have been reduced by PA, particularly in the setting of a PBM
      program.

PMID- 27873341
TI  - Immunostain use in the diagnosis of melanomas referred to a tertiary medical
      center: a 15-year retrospective review (2001-2015).
AB  - BACKGROUND: Little is known regarding the clinical practice of
      immunohistochemistry in the diagnosis of melanoma. We aimed to assess the
      incidence of immunostain usage by referring pathologists and dermatopathologists
      in melanoma cases sent for consultative review. As a secondary objective,
      associations between immunostain use and specific melanoma characteristics were
      also evaluated. METHODS: This is a retrospective review of consultation reports
      of referred melanomas at a tertiary academic center in New York, NY from 2001 to
      2015. Univariate regression analysis was performed on melanomas with accompanying
      immunostains and on characteristics such as Breslow's depth, location, prognostic
      factors and morphologic subtypes. Associations between immunostain usage and
      these characteristics were analyzed using Fisher's exact test. RESULTS:
      Immunostain use significantly increased over the study period (p < 0.001) and was
      more likely to be associated with melanomas that were thicker [odds ratio (OR) =
      2.5; 1.7-3.6]; located on the head and neck (OR = 1.6; 1.4-1.9) or acral sites
      (OR = 1.5; 1.1-2.0); had ulceration (OR = 2.1; 1.6-2.8), dermal mitoses (OR =
      1.3; 1.1-1.5), or perineural invasion (OR = 3.6; 2.0-6.5); or were of
      desmoplastic (OR = 7.4; 4.5-12), amelanotic (OR = 7.1; 3.6-14), or nevoid
      subtypes (OR = 4.0; 1.7-8.9). CONCLUSIONS: Immunostain use in the diagnosis of
      melanoma has increased significantly in the past 15 years for reasons that remain
      unclear.

PMID- 27873342
TI  - Inconsistency and drop-minimum data analysis.
AB  - Even though consistency is an important issue in multi-regional clinical trials
      and inconsistency is often anticipated, solutions for handling inconsistency are
      rare. If a region's treatment effects are inconsistent with that of the other
      regions, pooling all the regions to estimate the overall treatment effect may not
      be reasonable. Unlike the multiple center clinical trials conducted in the USA
      and Europe, in multi-regional clinical trials, different regional regulatory
      agencies may have their own ways to interpret data and approve new drugs. It is
      therefore practical to consider the case in which the data from the region with
      the minimal observed treatment effect is excluded from the analysis in order to
      attain the regulatory approval of the study drug. Under such cases, what is the
      appropriate statistical approach for the remaining regions? We provide a solution
      first formulated within the fixed effects framework and then extend it to
      discrete random effects models. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27873343
TI  - A time-varying effect model for examining group differences in trajectories of
      zero-inflated count outcomes with applications in substance abuse research.
AB  - This study proposes a time-varying effect model for examining group differences
      in trajectories of zero-inflated count outcomes. The motivating example
      demonstrates that this zero-inflated Poisson model allows investigators to study
      group differences in different aspects of substance use (e.g., the probability of
      abstinence and the quantity of alcohol use) simultaneously. The simulation study
      shows that the accuracy of estimation of trajectory functions improves as the
      sample size increases; the accuracy under equal group sizes is only higher when
      the sample size is small (100). In terms of the performance of the hypothesis
      testing, the type I error rates are close to their corresponding significance
      levels under all settings. Furthermore, the power increases as the alternative
      hypothesis deviates more from the null hypothesis, and the rate of this
      increasing trend is higher when the sample size is larger. Moreover, the
      hypothesis test for the group difference in the zero component tends to be less
      powerful than the test for the group difference in the Poisson component.
      Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27873344
TI  - Impact of Residual Mitral Regurgitation on Right Ventricular Systolic Function
      After Left Ventricular Assist Device Implantation.
AB  - Significant mitral regurgitation (MR) is thought to decrease after left
      ventricular assist device (LVAD) implantation, and therefore repair of mitral
      valve is not indicated in current practice. However, residual moderate and severe
      MR leads to pulmonary artery pressure increase, thereby resulting in right
      ventricular (RV) dysfunction during follow-up. We examined the impact of residual
      MR on systolic function of the right ventricle by echocardiography after LVAD
      implantation. This study included 90 patients (mean age: 51.7 +/- 10.9 years,
      14.4% female) who underwent LVAD implantation (HeartMate II = 21, HeartWare = 69)
      in a single center between December 2010 and June 2014. Echocardiograms obtained
      at 3-6 months and over after implantation were analyzed retrospectively. RV
      systolic function was graded as normal, mild, moderate, and severely depressed.
      MR (>=moderate) was observed in 43 and 44% of patients at early and late period,
      respectively. Systolic function of the RV was severely depressed in 16 and 9% of
      all patients. Initial analysis (mean duration of support 174.3 +/- 42.5 days)
      showed a statistically significant correlation between less MR and improved
      systolic function of RV (P = 0.01). Secondary echocardiographic analysis
      (following a mean duration of support of 435.1 +/- 203 days) was also
      statistically significant for MR degree and RV systolic dysfunction (P = 0.008).
      Residual MR after LVAD implantation may cause deterioration of RV systolic
      function and cause right-sided heart failure symptoms. Repair of severe MR, in
      selected patients such as those with severe pulmonary hypertension and depressed
      RV, may be considered to improve the patient's clinical course during pump
      support.

PMID- 27873346
TI  - Characterization of endogenous promoters for control of recombinant gene
      expression in Acidithiobacillus ferrooxidans.
AB  - Acidithiobacillus ferrooxidans is an important iron- and sulfur-oxidizing
      acidophilic chemolithoautotroph that is used extensively in metal extraction and
      refining, and more recently in the bioproduction of chemicals. However, a lack of
      genetic tools has limited the further development of this organism for industrial
      bioprocesses. Using prior microarray studies that identified genes, which may
      express differentially in response to the availability of iron and sulfur, the
      cycA1 and tusA promoter sequences have been characterized for their ability to
      drive green fluorescent protein expression. The promoters exhibited opposite
      control behavior, where the cycA1 sequence was repressed and the tusA promoter
      was induced by the presence of sulfur in the growth medium. Sulfur was found to
      be the dominant signal. The sulfur IC50 for cycA1 was 0.56 mM (18 mg/L), whereas
      the sulfur EC50 of tusA was 2.5 mM (80 mg/L). Together these sequences provide
      two new tools to selectively induce or repress gene expression in A.
      ferrooxidans. Acidithiobacillus ferrooxidans is an important industrial organism;
      however, genetic tools for control of gene expression do not exist. Here, we
      report the identification of promoter sequences that allow for the development of
      control of gene expression for engineering this organism.

PMID- 27873345
TI  - The prevalence of olfactory dysfunction in chronic rhinosinusitis.
AB  - OBJECTIVES: Many studies have reported that olfactory dysfunction frequently
      occurs in chronic rhinosinusitis (CRS) populations; however, the prevalence and
      degree of olfactory loss has not been systematically studied. The aims of this
      study were to use combined data to report the prevalence of olfactory dysfunction
      and to calculate weighted averages of olfactory test scores in CRS patients. DATA
      SOURCES: A search was conducted in PubMed and Scopus, following the methods of
      Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines.
      REVIEW METHODS: Studies reporting the prevalence of olfactory dysfunction using
      objective measures or olfactory test scores using validated scales were included.
      RESULTS: A total of 47 articles were included in a systematic review and 35 in
      the pooled data analysis. The prevalence of olfactory dysfunction in chronic
      rhinosinusitis was found to be 30.0% using the Brief Smell Identification Test,
      67.0% using the 40-item Smell Identification Test, and 78.2% using the total
      Sniffin' Sticks score. Weighted averages +/- standard deviation of olfactory test
      scores were 25.96 +/- 7.11 using the 40-item Smell Identification Test, 8.60 +/-
      2.81 using the Brief Smell Identification Test, 21.96 +/- 8.88 using total
      Sniffin' Sticks score, 5.65 +/- 1.51 using Sniffin' Sticks-Threshold, 9.21 +/-
      4.63 using Sniffin' Sticks-Discrimination, 9.47 +/- 3.92 using Sniffin' Sticks
      Identification, and 8.90 +/- 5.14 using the Questionnaire for Olfactory Disorders
      Negative Statements. CONCLUSIONS: In CRS populations, a significant percentage of
      patients experience olfactory dysfunction, and mean olfactory scores are within
      the dysosmic range. Laryngoscope, 2016 127:309-320, 2017.

PMID- 27873347
TI  - Infantile Hemangioma with Minimal or Arrested Growth: Further Observations on
      Clinical and Histopathologic Findings of this Unique but Underrecognized Entity.
AB  - BACKGROUND: Infantile hemangioma (IH) with minimal or arrested growth (IH-MAG) is
      becoming increasingly recognized in the literature. It is important to be aware
      of their existence, because the correct diagnosis is essential for
      prognostication and treatment and, in the case of facial segmental lesions, the
      direction of further investigations if PHACE (posterior fossa abnormalities and
      other structural brain abnormalities; hemangioma(s) of the cervical facial
      region; arterial cerebrovascular anomalies; cardiac defects, aortic coarctation,
      and other aortic abnormalities; eye anomalies) syndrome or Sturge-Weber syndrome
      is suspected. Although the clinical and histologic characteristics of IH-MAG
      resemble capillary malformations, positive GLUT-1 status is a delineating
      feature. METHODS: We reviewed nine cases of infants who presented after 2000 with
      birthmarks showing unique clinical features suggestive of a special variant of
      IHs. All patients had serial photographs taken demonstrating resolution of the
      birthmark over time. Five of these cases had skin biopsy performed, all of which
      confirmed GLUT-1 positivity. RESULTS: This photographic series of IH-MAG
      demonstrates their unique clinical, histologic, and immunochemistry features.
      They were nearly fully formed at birth, and their common clinical features
      included telangiectasia, venules, and matte erythema with light and dark areas.
      Spontaneous resolution over time without cosmetic disfigurement was the observed
      natural history in the majority of cases. CONCLUSION: IH-MAG is a unique clinical
      subset of hemangioma for which close observation is the preferred treatment. When
      in doubt, a biopsy for histology and GLUT-1 status may be needed to confirm the
      diagnosis before embarking on unnecessary laser treatment or medical
      interventions.

PMID- 27873348
TI  - Reply.

PMID- 27873349
TI  - Not Only Size Matters: Early-Talker and Late-Talker Vocabularies Support
      Different Word-Learning Biases in Babies and Networks.
AB  - In typical development, word learning goes from slow and laborious to fast and
      seemingly effortless. Typically developing 2-year-olds seem to intuit the whole
      range of things in a category from hearing a single instance named-they have word
      learning biases. This is not the case for children with relatively small
      vocabularies (late talkers). We present a computational model that accounts for
      the emergence of word-learning biases in children at both ends of the vocabulary
      spectrum based solely on vocabulary structure. The results of Experiment 1 show
      that late-talkers' and early-talkers' noun vocabularies have different structures
      and that neural networks trained on the vocabularies of individual late talkers
      acquire different word-learning biases than those trained on early-talker
      vocabularies. These models make novel predictions about the word-learning biases
      in these two populations. Experiment 2 tests these predictions on late- and early
      talking toddlers in a novel noun generalization task.

PMID- 27873350
TI  - Is command following unrelated to top-down attention in consciousness disorders?

PMID- 27873351
TI  - Rasch analysis of the carers quality of life questionnaire for parkinsonism.
AB  - OBJECTIVE: To assess the psychometric properties of the Carers Quality of Life
      Questionnaire for Parkinsonism using a Rasch modeling approach and determine the
      optimal cut-off score. METHODS: We performed a Rasch analysis of the survey
      answers of 430 carers of patients with atypical parkinsonism. RESULTS: All of the
      scale items demonstrated acceptable goodness of fit to the Rasch model. The scale
      was unidimensional and no notable differential item functioning was detected in
      the items regarding age and disease type. Rating categories were functioning
      adequately in all scale items. The scale had high reliability (.95) and construct
      validity and a high degree of precision, distinguishing between 5 distinct groups
      of carers with different levels of quality of life. A cut-off score of 62 was
      found to have the optimal screening accuracy based on Hospital Anxiety and
      Depression Scale subscores. CONCLUSION: The results suggest that the Carers
      Quality of Life Questionnaire for Parkinsonism is a useful scale to assess
      carers' quality of life and allows analyses requiring interval scaling of
      variables. (c) 2016 International Parkinson and Movement Disorder Society.

PMID- 27873353
TI  - Adaptively Optimized Combination (AOC) of Phased-Array MR Spectroscopy Data in
      the Presence of Correlated Noise: Compared with Noise-Decorrelated or Whitened
      Methods.
AB  - PURPOSE: A method for adaptively optimized combination (AOC) of MR spectroscopic
      data from a coil array was recently introduced. The superior performance of the
      AOC method is evident when compared with the methods that assume uncorrelated
      noise between coil elements. However, it is unclear whether the AOC method
      represents the most optimal combination in the presence of correlated noise, when
      compared with the noise-decorrelated or whitened methods that specifically tackle
      the correlated noise between coil elements. METHODS: A new, unified theoretical
      framework was developed to illustrate the relationship between the AOC method and
      three noise-decorrelated or whitened methods, namely, noise-decorrelated
      combination (nd-comb), whitened singular value decomposition (WSVD), and improved
      WSVD (WSVD+Apod). Simulation-based comparisons and in vivo human brain
      experiments on a 3 Tesla (T) MRI scanner were performed using an 8-channel phased
      array head coil. RESULTS: Compared with the noise-decorrelated or whitened
      methods, the AOC method consistently yielded the best combination in terms of the
      robustness against noise and maintaining the combined spectrum from distortion,
      and the superior performance was most evident at a low signal-to-noise ratio
      (SNR). CONCLUSION: The AOC method represents the theoretical optimal combination
      in the presence of correlated noise between coil elements, whereas the three
      noise-decorrelated or whitened methods are asymptotically optimal. Magn Reson Med
      78:848-859, 2017. (c) 2016 International Society for Magnetic Resonance in
      Medicine.

PMID- 27873352
TI  - Assessment of the Fecal Microbiota in Beef Calves.
AB  - BACKGROUND: There is increasing interest in the fecal microbiota, but study in
      calves has been limited. HYPOTHESIS/OBJECTIVES: To evaluate the fecal microbiota
      of beef calves and cows on different farms, and to preliminarily explore the
      impact of antimicrobial exposure. ANIMALS: A total of 172 animals, 156 (91%)
      calves and 16 (9.3%) cows, were enrolled from 5 cow-calf farms. METHODS: The
      fecal bacterial microbiota was assessed through sequencing of 16S rRNA gene (V4
      region) amplicons. RESULTS: There were significant differences in the relative
      abundances of numerous phyla between calves on different farms. Farms could be
      separated into 2 groups: 1 (farms B and C) dominated by Firmicutes and 1 (farms
      A, D, and E) with predominance of Proteobacteria and Actinobacteria. Richness
      (median 2,974 versus 1,477, P = .008), diversity (51.4 versus 29.1, P = .0029),
      and evenness (0.73 versus 0.68, P = .006) were higher in cows. Over-represented
      operational taxonomic units (OTUs) in cows tended to be from the classes Bacilli
      and Bacteroidia, whereas Clostridia and Actinobacteria were most prominently over
      represented in calves. There were differences in community membership (P = .028)
      and structure (P = .029) in calves that had a history of antimicrobial exposure
      compared those that did not. Eight (89%) over-represented OTUs in the untreated
      group were Firmicutes (7 from the order Clostridiales), compared to only 3 (38%)
      (2 Clostridiales) in the untreated group. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Interfarm variation should be investigated to determine the causes and potential
      implications for health and production. Antimicrobial exposure may have an impact
      on the fecal microbiota at individual and farm levels.

PMID- 27873355
TI  - Isoquercitrin protects against pulmonary hypertension via inhibiting PASMCs
      proliferation.
AB  - Pulmonary vascular remodelling is a common feature among the heterogeneous
      disorders that cause pulmonary arterial hypertension (PAH), and pulmonary
      arterial smooth muscle cells (PASMCs) proliferation impact the long-term
      prognosis of the patient. Isoquercitrin (IQC) is a flavonoid with anti-oxidative,
      anti-inflammatory and anti-proliferative activations. This study aimed to
      investigate whether IQC could prevent PASMCs proliferation and vascular
      remodelling in monocrotaline (MCT) induced PAH. Male Wistar rats were
      administered with Vehicle or 0.1% IQC maintain feed after MCT (40 mg/kg)
      injection. Haemodynamic changes, right ventricular hypertrophy and lung
      morphological features were assessed 3 weeks later. MCT-induced PAH, pulmonary
      vascular remodelling and PASMCs proliferation in Vehicle-treated rats. IQC
      reduced the right ventricle systolic pressure (RVSP), the ratio of RV/LV+S and
      the RV hypertrophy. IQC significantly alleviated the expression of proliferating
      cell nuclear antigen (PCNA), smooth muscle alpha-actin (alpha-SMA), and the
      percentage of fully muscularized small arterioles. In vitro studies, PASMCs were
      pretreated with IQC and stimulated with platelet-derived growth factor (PDGF)-BB
      (20 ng/mL). IQC suppressed PDGF-BB-induced PASMCs proliferation and caused G0/G1
      phase cell cycle arrest. IQC downregulated the expression of Cyclin D1 and CDK4
      as well as inhibited p27Kip1 degradation. Meanwhile, IQC negatively modulated
      PDGF-BB-induced phosphorylation of PDGF-Rbeta, Akt/GSK3beta and ERK1/2. IQC
      ameliorated MCT-induced pulmonary vascular remodelling via suppressing PASMCs
      proliferation and blocking PDGF-Rbeta signalling pathway.

PMID- 27873354
TI  - Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice.
AB  - The gastroprotective effect of esculin was investigated in a mouse model of
      ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and
      20 mg/kg body weight prior to ethanol ingestion led to significant
      gastroprotection compared with untreated mice. Gastric mucosal lesions were
      evaluated by macroscopic and histopathological alterations, lesion index, and
      myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced
      macroscopic and histopathological damage, gastric lesion index, and MPO activity
      in a dose-dependent manner. Moreover, esculin significantly reduced nitric oxide
      (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor-kappa B
      (NF-kappaB) p65 protein expression in gastric tissues after ethanol challenge.
      Analysis of inflammatory cytokines indicated that esculin pretreatment markedly
      suppressed the increased expression of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6) in ethanol-treated mice. The results demonstrate a
      protective effect of esculin against gastric injury and suggest that the
      underlying mechanism might be associated with inhibition of NF-kappaB activation,
      which subsequently reduces expression of iNOS, TNF-alpha, and IL-6.

PMID- 27873357
TI  - Use of big data for drug development and for public and personal health and care.
AB  - The use of data analytics across the entire healthcare value chain, from drug
      discovery and development through epidemiology to informed clinical decision for
      patients or policy making for public health, has seen an explosion in the recent
      years. The increase in quantity and variety of data available together with the
      improvement of storing capabilities and analytical tools offer numerous
      possibilities to all stakeholders (manufacturers, regulators, payers, healthcare
      providers, decision makers, researchers) but most importantly, it has the
      potential to improve general health outcomes if we learn how to exploit it in the
      right way. This article looks at the different sources of data and the importance
      of unstructured data. It goes on to summarize current and potential future uses
      in drug discovery, development, and monitoring as well as in public and personal
      healthcare; including examples of good practice and recent developments. Finally,
      we discuss the main practical and ethical challenges to unravel the full
      potential of big data in healthcare and conclude that all stakeholders need to
      work together towards the common goal of making sense of the available data for
      the common good.

PMID- 27873358
TI  - Regarding 'WhatsApp is an effective tool for obtaining second opinion in oral
      pathology practice'.

PMID- 27873356
TI  - Nail Psoriasis: A Systematic Evaluation in 313 Children with Psoriasis.
AB  - BACKGROUND/OBJECTIVES: Little information is available on the prevalence and
      clinical aspects of nail involvement in children with psoriasis. The objective of
      this study was to evaluate the prevalence and clinical aspects of and the risk
      factors for nail involvement in French children with psoriasis. METHODS: We
      performed a multicenter, cross-sectional study in 23 French dermatology centers.
      All children seen during the 1-year study were systematically included. Clinical
      features of the nails were collected. Association with clinical aspects of the
      disease and comorbidities were evaluated. RESULTS: Of 313 children with psoriasis
      (mean age 9.1 +/- 4.2 yrs; 149 boys, 164 girls), 31.1% had familial psoriasis and
      30% had severe psoriasis. The mean age at onset was 6.1 +/- 3.7 years. Nails were
      involved in 32.3% of children. The main clinical aspects were pitting (69.1%) for
      fingernails and onycholysis (40.0%) and pachyonychia (27.5%) for toenails. All of
      the fingers were involved at similar frequencies, whereas the big toe was
      involved twice as often as the others (p < 0.005). Nail involvement was
      associated with male sex (p < 0.001), palmoplantar psoriatic (p < 0.001),
      severity of disease (p = 0.003), and psoriatic arthritis (p = 0.03). CONCLUSION:
      The prevalence of nail involvement was 32.3% in children with psoriasis. Clinical
      aspects in children are reported, as well as clinical associations. As in adults,
      nail psoriasis is closely associated with psoriatic arthritis.

PMID- 27873359
TI  - Constipation in parkinson's disease: Subjective symptoms, objective markers, and
      new perspectives.
AB  - Constipation is among the first nonmotor symptoms to develop in the prodromal
      phase of PD. Pathological alpha-synuclein deposition is present throughout the
      gastrointestinal tract up to 20 years preceding diagnosis. Nevertheless,
      constipation in the context of PD remains ill defined and poorly understood. In
      this review, we summarize current knowledge of subjective symptoms and objective
      measures of constipation in PD. More than 10 different definitions of
      constipation have been used in the PD literature, making generalizations
      difficult. When pooling results from the most homogeneous studies in PD, a median
      constipation prevalence of 40% to 50% emerges, but with large variation across
      individual studies. Also, constipation prevalence tends to increase with disease
      progression. A similar prevalence is observed among patients with idiopathic
      rapid eye movement sleep behavior disorder. Interestingly, we detected a
      correlation between constipation prevalence in PD patients and healthy control
      groups in individual studies, raising concerns about how various constipation
      questionnaires are implemented across study populations. More than 80% of PD
      patients exhibit prolonged colonic transit time, and the same is probably true
      for de novo PD patients. Thus, the prevalence of objective colonic dysfunction
      exceeds the prevalence of subjective constipation. Colonic transit time measures
      are simple, widely available, and hold promise as a useful biomarker in manifest
      PD. More research is needed to elucidate the role of gastrointestinal dysfunction
      in disease progression of PD. Moreover, colonic transit measures may have utility
      as a more accurate risk factor for predicting PD in the prodromal phase. (c) 2016
      International Parkinson and Movement Disorder Society.

PMID- 27873360
TI  - Personal measurement of exposure to black carbon and ultrafine particles in
      schoolchildren from PARIS cohort (Paris, France).
AB  - This study aimed to measure in French children personal exposure concentrations
      of black carbon (BC) and ultrafine particles (UFP) and to quantify the
      contribution of different microenvironments (home, school, places of
      extracurricular activities, transport) to their total exposure. It was conducted
      on 96 9-year-old children from the PARIS birth cohort. BC and UFP were
      continuously measured by portable devices (microAeth(r) AE51 and DiSCmini(r) )
      for a minimum of 24 hours, while participating families simultaneously filled in
      a space-time-activities-budget questionnaire. BC exposure concentration was
      higher during trips (principally metro/train and bus), while UFP exposure
      concentration was higher during indoor activities (mainly eating at restaurants)
      and in trips. The most important UFP peaks were measured at home, especially
      during cooking. Home and school together accounted for much of the total
      exposure, 83.8% for BC and 85.3% for UFP. The contribution of transport to total
      exposure was 12.4% for BC and 9.7% for UFP, while extracurricular activities were
      responsible for 3.8% and 5% of the total exposure to BC and UFP, respectively.

PMID- 27873361
TI  - Effect of HIV infection in the micronuclei frequency on the oral mucosa.
AB  - BACKGROUND: The genotoxic impact of HIV infection on the oral cavity malignancies
      is unknown. The aim of this study was to evaluate the effect of HIV infection in
      micronucleus (MN) frequency on the oral mucosa of HIV+ patients and establish a
      relationship with early cytogenetic changes in oral carcinogenesis. METHODS:
      Thirty HIV+ individuals who are under highly active antiretroviral therapy
      (HAART) and 30 non-HIV patients were evaluated. Two smears were taken from the
      lateral border of the tongue and mouth floor and stained by Feulgen. The
      frequency of MN was examined in 3000 cells per subject under common microscopy.
      RESULTS: MN analysis showed no significant difference between groups by Mann
      Whitney U-test for total MNs (P = 0.178). The presence of single MN was greater
      in control group with statistical significance (P = 0.009), while in HIV group,
      multiple MNs were exhibited in higher mean. CONCLUSIONS: HIV patients under HAART
      therapy and low viral load values showed higher frequency of multiple MNs, which,
      although not statistically significant, may be caused by the action of the Vpr
      gene, an accessory gene of HIV. These results corroborate the theory of HIV
      infection cytogenetic damage.

PMID- 27873363
TI  - Iron(II), Cobalt(II), Nickel(II), and Zinc(II) Silylene Complexes: Reaction of
      the Silylene [iPrNC(NiPr2 )NiPr]2 Si with FeBr2 , CoBr2 , NiBr2 ?MeOCH2 CH2 OMe,
      ZnCl2 , and ZnBr2.
AB  - Reaction of the donor-stabilized silylene [iPrNC(NiPr2 )NiPr]2 Si (1) with FeBr2
      , CoBr2 , NiBr2 ?MeOCH2 CH2 OMe, ZnCl2 , and ZnBr2 afforded the respective
      transition-metal silylene complexes 4-8, the formation of which can be described
      in terms of a Lewis acid/base reaction (4, 5, 7, 8) or a nucleophilic
      substitution reaction (6). However, the reactivity profile of silylene 1 is not
      only based on its strong Lewis base character; the different coordination modes
      of the two guanidinato ligands (4-6 vs. 7 and 8) add an additional reactivity
      facet. The paramagnetic compounds 4 and 5 and the diamagnetic compounds 6?THF, 7,
      and 8?0.5 Et2 O were structurally characterized by single-crystal X-ray
      diffraction. In addition, compound 6?THF was studied by 15 N and 29 Si solid
      state NMR spectroscopy, and 7 and 8 were characterized by NMR spectroscopic
      studies in the solid state (15 N, 29 Si) and in solution (1 H, 13 C, 29 Si).
      Compounds 4-8 represent very rare examples of FeII , CoII , NiII , and ZnII
      silylene complexes. Four-coordinate silicon(II) compounds with an SiN3 M skeleton
      (M=Fe, Co, Ni) and M in the formal oxidation state +2 (4-6) have not yet been
      reported, and five-coordinate silicon(II) compounds with an SiN4 Zn skeleton (7,
      8) are also unprecedented.

PMID- 27873362
TI  - Influence of Mesenchymal Stem Cells Conditioned Media on Proliferation of Urinary
      Tract Cancer Cell Lines and Their Sensitivity to Ciprofloxacin.
AB  - Mesenchymal stem cells (MSCs) are known to interact with cancer cells through
      direct cell-to-cell contact and secretion of paracrine factors, although their
      exact influence on tumor progression in vivo remains unclear. To better
      understand how fetal and adult stem cells affect tumors, we analyzed viability of
      human renal (786-0) and bladder (T24) carcinoma cell lines cultured in
      conditioned media harvested from amniotic fluid-derived stem cells (AFSCs) and
      adipose-derived stem cells (ASCs). Both media reduced metabolic activity of 786-0
      cells, however, decreased viability of T24 cells was noted only after incubation
      with conditioned medium from ASCs. To test the hypothesis that MSCs-secreted
      factors might be involved in chemoresistance acquisition, we further analyzed
      influence of mesenchymal stem cell conditioned media (MSC-CM) on cancer cells
      sensitivity to ciprofloxacin, that is considered as potential candidate agent for
      urinary tract cancers treatment. Significantly increased resistance to tested
      drug indicates that MSCs may protect cancer cells from chemotherapy. J. Cell.
      Biochem. 118: 1361-1368, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27873364
TI  - Modelling the effect of hydration on skin conductivity.
AB  - BACKGROUND: Electrical signals are recorded from and sent into the body via the
      skin in a number of applications. In practice, skin is often hydrated with
      liquids having different conductivities so a model was produced in order to
      determine the relationship between skin impedance and conductivity. METHODS: A
      model representing the skin was subjected to a variety of electrical signals. The
      parts of the model representing the stratum corneum were given different
      conductivities to represent different levels of hydration. RESULTS: The overall
      impedance and conductivity of the cells did not vary at frequencies below 40 kHz.
      Above 40 kHz, levels of increased conductivity caused the overall impedance to
      decrease. CONCLUSION: The variation in impedance with conductivity between 5 and
      50 mSm-1 can be modelled quadratically while variation in impedance with
      conductivity between 5 and 5000 mSm-1 can be modelled with a double exponential
      decay.

PMID- 27873365
TI  - Mechanisms for cell-to-cell propagation no longer lag behind.

PMID- 27873366
TI  - Monochorionic diamniotic twin pregnancy with selective fetal growth restriction
      Type II: sonographic and fetoscopic findings of poor prognosis.

PMID- 27873367
TI  - miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by
      regulating monocarboxylate transporter 1.
AB  - Remyelination is limited in patients with multiple sclerosis (MS) due to the
      difficulties in recruiting proliferating oligodendrocyte precursors (OPCs), the
      inhibition of OPC differentiation and/or maturation, and/or failure in the
      generation of the myelin sheath. In vitro studies have revealed that miR-219 is
      necessary for OPC differentiation and monocarboxylate transporter 1 (MCT1) plays
      a vital role in oligodendrocyte maturation and myelin synthesis. Herein, we
      hypothesized that miR-219 might promote oligodendrocyte differentiation and
      attenuate demyelination in a cuprizone (CPZ)-induced demyelinated model by
      regulating the expression of MCT1. We found that CPZ-treated mice exhibited
      significantly increased anxiety in the open field test. However, miR-219 reduced
      anxiety as shown by an increase in the total distance, the central distance and
      the mean amount of time spent in the central area. miR-219 decreased the quantity
      of OPCs and increased the number of oligodendrocytes and the level of myelin
      basic protein (MBP) and cyclic nucleotide 3' phosphodiesterase (CNP) protein.
      Ultrastructural studies further confirmed that the extent of demyelination was
      attenuated by miR-219 overexpression. Meanwhile, miR-219 also greatly enhanced
      MCT1 expression via suppression of oligodendrocyte differentiation inhibitors,
      Sox6 and Hes5, treatment with the MCT1 inhibitor alpha-cyano-4-hydroxycinnamate
      (4-CIN) reduced the number of oligodendrocytes and the protein levels of MBP and
      CNP. Taken together, these results suggest a novel mode of action of miR-219 via
      MCT1 in vivo and may provide a new potential remyelination therapeutic target.

PMID- 27873369
TI  - The genetic architecture of novel trophic specialists: larger effect sizes are
      associated with exceptional oral jaw diversification in a pupfish adaptive
      radiation.
AB  - The genetic architecture of adaptation is fundamental to understanding the
      mechanisms and constraints governing diversification. However, most case studies
      focus on loss of complex traits or parallel speciation in similar environments.
      It is still unclear how the genetic architecture of these local adaptive
      processes compares to the architecture of evolutionary transitions contributing
      to morphological and ecological novelty. Here, we identify quantitative trait
      loci (QTL) between two trophic specialists in an excellent case study for
      examining the origins of ecological novelty: a sympatric radiation of pupfishes
      endemic to San Salvador Island, Bahamas, containing a large-jawed scale-eater and
      a short-jawed molluscivore with a skeletal nasal protrusion. These specialized
      niches and trophic traits are unique among over 2000 related species.
      Measurements of the fitness landscape on San Salvador demonstrate multiple
      fitness peaks and a larger fitness valley isolating the scale-eater from the
      putative ancestral intermediate phenotype of the generalist, suggesting that more
      large-effect QTL should contribute to its unique phenotype. We evaluated this
      prediction using an F2 intercross between these specialists. We present the first
      linkage map for pupfishes and detect significant QTL for sex and eight skeletal
      traits. Large-effect QTL contributed more to enlarged scale-eater jaws than the
      molluscivore nasal protrusion, consistent with predictions from the adaptive
      landscape. The microevolutionary genetic architecture of large-effect QTL for
      oral jaws parallels the exceptional diversification rates of oral jaws within the
      San Salvador radiation observed over macroevolutionary timescales and may have
      facilitated exceptional trophic novelty in this system.

PMID- 27873368
TI  - Why is alcohol cancer's best-kept secret?

PMID- 27873371
TI  - Getting a Sporting Chance: Title IX and the Intergenerational Transmission of
      Health.
AB  - We know that healthier mothers tend to have healthier infants, but we do not know
      how much of that relationship reflects the intergenerational transmission of
      genetic attributes versus environmental influences. From a policy perspective, it
      is crucial to understand which environmental influences are important and whether
      investments in one generation affect outcomes for the next. I use variation in
      the implementation of Title IX to measure the effects of increased athletic
      opportunities on the health of infants. Babies born to women with greater
      athletic opportunities as teenagers have babies that are healthier at birth. They
      are less likely to be born of low or very low birthweight and have higher Apgar
      scores. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27873370
TI  - Magnitude of change in fetal cerebroplacental ratio in third trimester and risk
      of adverse pregnancy outcome.
AB  - OBJECTIVES: To evaluate whether the magnitude of change in the cerebroplacental
      ratio (CPR) after 30 weeks' gestation is a better predictor of adverse pregnancy
      outcome compared with a single CPR measurement at 35-37 weeks. A secondary aim
      was to evaluate whether the utility of CPR at 35-37 weeks was enhanced after
      adjusting for change in gestational age. METHODS: This was a retrospective cohort
      study of women who had at least two ultrasound scans between 30 and 37 weeks'
      gestation, with the final scan at 35-37 weeks. Exclusion criteria were major
      congenital abnormality, aneuploidy, multiple pregnancy and unknown middle
      cerebral artery pulsatility index or umbilical artery pulsatility index. A normal
      reference range for CPR was derived from a separate cohort of women with normal
      outcome and a Generalised Additive Model for Location, Scale and Shape was fitted
      to derive standardized centiles. These reference centiles were then used to
      calculate Z-scores for the study cohort. Logistic regression models and receiver
      operating characteristics (ROC) curves were used to evaluate the predictive
      utility of CPR Z-score at last CPR measurement and the change in CPR on mode of
      delivery, neonatal outcome and composite neonatal outcome. The area under the ROC
      curve (AUC) for each model was compared before and after adjustment for parity,
      hypertension, diabetes, body mass index and smoking status. RESULTS: A total of
      1860 women met the inclusion criteria. There was no association between the
      magnitude of change in CPR and composite adverse pregnancy outcome (P = 0.92). Of
      the outcomes that made up the composite, an increase in CPR Z-score over time was
      associated with a lower risk for emergency Cesarean delivery (P < 0.001) and
      emergency Cesarean delivery for non-reassuring fetal status (P = 0.02). It was
      also associated with a lower risk of birth weight < 10th centile (P = 0.01) and
      hypoglycemia (P = 0.001). There was no significant difference between the AUCs of
      last CPR Z-score and last CPR Z-score adjusted for the change in gestational age
      in predicting pregnancies at risk for adverse outcome. CONCLUSIONS: Our results
      suggest that both the individual CPR Z-score and the magnitude and direction of
      change in CPR Z-score can identify pregnancies at risk of various adverse
      perinatal outcomes. However, the CPR Z-score at 35-37 weeks' gestation appears to
      be a better predictor. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons
      Ltd.

PMID- 27873372
TI  - Palladium-Catalyzed Tandem Oxidative Arylation/Olefination of Aromatic Tethered
      Alkenes/Alkynes.
AB  - We describe herein a palladium-catalyzed tandem oxidative arylation/olefination
      reaction of aromatic tethered alkenes/alkynes for the synthesis of
      dihydrobenzofurans and 2 H-chromene derivatives. This reaction features a 1,2
      difunctionalization of C-C pi-bond with two C-H bonds using O2 as terminal
      oxidant at room temperature. The products obtained are valuable synthons and
      important scaffolds in biological agents and natural products.

PMID- 27873373
TI  - Cardiac output and blood flow redistribution in fetuses with D-loop transposition
      of the great arteries and intact ventricular septum: insights into
      pathophysiology.
AB  - OBJECTIVES: Although the postnatal physiology of D-loop transposition of the
      great arteries with intact ventricular septum (D-TGA/IVS) is well established,
      little is known about fetal D-TGA/IVS. In the normal fetus, the pulmonary valve
      (PV) is larger than the aortic valve (AoV), there is exclusive right-to-left flow
      at the foramen ovale (FO) and ductus arteriosus (DA), and the left ventricle (LV)
      ejects 40% of combined ventricular output (CVO) through the aorta, primarily to
      the brain. In D-TGA/IVS, the LV ejects oxygen-rich blood to the pulmonary artery,
      theoretically leading to pulmonary vasodilation, increased branch pulmonary
      artery flow and reduced DA flow. In this study, we tested the hypothesis that D
      TGA/IVS anatomy results in altered cardiac valve sizes, ventricular contribution
      to CVO, and FO and DA flow direction. METHODS: Seventy-four fetuses with D
      TGA/IVS that underwent fetal echocardiography at our institution between 2004 and
      2015 were included in the study. AoV, PV, mitral valve and tricuspid valve sizes
      were measured and Z-scores indexed to gestational age were generated. Ventricular
      output was calculated using Doppler-derived velocity-time integral, and direction
      of flow at the FO and DA shunts was recorded in each fetus using both color
      Doppler and flap direction. Measurements in the D-TGA/IVS fetuses were compared
      with data of 222 controls, matched for gestational-age range, from our
      institutional normal fetal database. RESULTS: The LV component of CVO was higher
      in D-TGA/IVS fetuses than in controls (50.7% vs 40.2%; P < 0.0001), with no
      difference in the total CVO. Flow was bidirectional at the FO in 56 (75.7%) and
      at the DA in 24 (32.4%) D-TGA/IVS fetuses. Only 21.6% fetuses had normal right-to
      left flow at both shunts. Bidirectional shunting was more common in third
      trimester fetuses than in second-trimester ones (P < 0.03). AoV and PV diameters
      were nearly identical in D-TGA/IVS in contrast to control fetuses, hence AoV Z
      score was higher than PV Z-score (1.13 vs -0.65, P < 0.0001) in D-TGA/IVS.
      CONCLUSIONS: In fetuses with D-TGA/IVS there is loss of the normal right-sided
      dominance, as each ventricle provides half of the CVO, with a relatively large
      AoV diameter and a small PV diameter, and high incidence of bidirectional FO and
      DA flow. This may support the theory that high pulmonary artery oxygen content
      reduces pulmonary vascular resistance, thereby increasing branch pulmonary artery
      flow and venous return, which results in increased LV preload and output.
      Pulmonary sensitivity to oxygen is thought to increase later in gestation, which
      may explain the higher incidence of bidirectional shunting. Consequences of these
      flow alterations include increased aortic and, most likely, brain flow, perhaps
      in an attempt to compensate for the substrate deficiency observed in D-TGA/IVS.
      Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 27873375
TI  - Desistance mandates compared with treatment mandates in criminal justice
      populations.

PMID- 27873374
TI  - The benefits of using the UPPS model of impulsivity rather than the Big Five when
      assessing the relationship between personality and problem gambling.

PMID- 27873376
TI  - Extended Long-Term Effects of Cervical Vagal Nerve Stimulation on Headache
      Intensity/Frequency and Affective/Cognitive Headache Perception in Drug Resistant
      Complex-Partial Seizure Patients.
AB  - OBJECTIVES: Invasive vagal nerve stimulation (iVNS) is an established treatment
      option for drug-resistant focal seizures and has been assumed to diminish
      frequent co-incidental daily headache/migraine. However, long-term effects on
      cognitive/affective head pain perception, headache intensity/frequency are
      lacking. We therefore investigated potential iVNS-induced effects in patients
      with drug-resistant focal seizure and daily headache/migraine. MATERIALS AND
      METHODS: A clinical database was used to select 325 patients with drug-resistant
      epilepsy treated by either iVNS plus best medical treatment (BMT) or BMT alone,
      compared to a healthy control group (HC). We assessed headache intensity (VAS),
      headache frequency, affective/cognitive pain perception (PASS; FSVA), migraine
      disability scores (MIDAS), sleep architecture (PSQI), depressive symptoms (BDI),
      and body weight (BMI). RESULTS: Nineteen patients with daily headache/migraine
      composed the clinical groups (10 iVNS and 9 BMT; iVNS mean age 49 years, range 36
      61 years; BMT mean age 45 years, range 23-63 years; equally distributed gender).
      Cervical iVNS was applied from 5-13 years (mean 8 years) with following
      stimulation patterns: 1.3 mA (0.5-2 mA), 20 Hz, 250 MUsec, 30 sec on/1.9 min off
      (0.5-5 min). The iVNS group had significantly lower VAS scores (iVNS 5.4; BMT
      7.8; p = 0.03) and PASS cognitive/anxiety subscores (iVNS 21; BMT 16; p = 0.02)
      compared to BMT and HC. Global PASS (p = 0.07), FSVA, PSQI, BDI, and BMI scores
      did not differ significantly between groups. CONCLUSIONS: iVNS appears to have
      positive modulatory long-term effects on headache and affective/cognitive head
      pain perception in patients with drug-resistant focal epilepsy, thus deserving
      further attention.

PMID- 27873378
TI  - Spotlights on our sister journals: Chem. Eur. J. 49/2016.

PMID- 27873377
TI  - The person-centred care of older people with cognitive impairment in acute care
      (POPAC) scale - psychometric evaluation.
AB  - AIM: To test the reliability and validity of the Person-centred care of Older
      People with cognitive impairment in Acute Care scale to determine nurses'
      perceptions of person-centred care. BACKGROUND: One-third of older adults
      admitted to hospital are at risk of serious hospital-acquired complications such
      as falls, infections and pressure injuries because of cognitive impairment. These
      risks can be reduced through person-centred practices. The Person-centred care of
      Older People with cognitive impairment in Acute Care scale is a self-report staff
      instrument to explore the extent to which person-centred practices are
      undertaken; however psychometric testing is limited. METHODS: A cross-sectional
      sample of acute care nurses (n = 240) in Queensland, Australia completing self
      report questionnaires. Psychometric analyses of item performance, reliability and
      validity were conducted. RESULTS: Item analysis revealed independent items. One
      item was removed due to negatively associating with the scale, improving total
      Cronbach's alpha from 0.76 to 0.84. The three original factors were maintained
      with regrouping of items. Confirmatory factor analysis confirmed the revised
      model. CONCLUSIONS: The revised Person-centred care of Older People with
      cognitive impairment in Acute Care scale had satisfactory psychometric properties
      when used as a total scale. IMPLICATIONS FOR NURSING MANAGEMENT: Scale brevity
      and simplicity together with rigorous development and testing indicates that the
      revised Person-centred care of Older People with cognitive impairment in Acute
      Care may be useful for quality improvement programmes into the care of older
      people in hospitals.

PMID- 27873379
TI  - Oxford's Systematic Review Initiative: leading by example in evidence-based
      transfusion medicine.

PMID- 27873380
TI  - Which costs of alcohol do policymakers care about?

PMID- 27873381
TI  - Cutting Edge Advances in Stem Cell Biology and Therapy.

PMID- 27873382
TI  - USE OF A NOVEL BOARD GAME IN A CLINICAL ROTATION FOR LEARNING THORACIC
      DIFFERENTIAL DIAGNOSES IN VETERINARY MEDICAL IMAGING.
AB  - When confronted with various findings on thoracic radiographs, fourth-year
      veterinary students often have difficulty generating appropriate lists of
      differential diagnoses. The purpose of this one-group, pretest, posttest
      experimental study was to determine if a game could be used as an adjunct
      teaching method to improve students' understanding of connections between imaging
      findings and differential diagnoses. A novel board game focusing on differential
      diagnoses in thoracic radiography was developed. One hundred fourth-year
      veterinary students took a brief pretest, played the board game, and took a brief
      posttest as a part of their respective clinical radiology rotations. Pretest
      results were compared to posttest results using a paired t-test to determine if
      playing the game impacted student understanding. Students' mean scores on the
      posttest were significantly higher than mean pretest scores (P < 0.0001). Thus,
      results indicate that playing the board game resulted in improved short-term
      understanding of thoracic differential diagnoses by fourth-year students, and use
      of the board game on a clinical rotation seems to be a beneficial part of the
      learning process.

PMID- 27873383
TI  - Building leadership capacity in advanced nurse practitioners - the role of
      organisational management.
AB  - AIM: To highlight the organisation-level management's role in building leadership
      capacity in advanced nurse practitioners and the need for appropriate supports to
      increase their becoming leaders. BACKGROUND: Little is published about the role
      of organisation-level management in building leadership capacity and in
      developing the next generation of nurse leaders. In times of economic constraint,
      organisations need to focus their efforts on targeted leadership initiatives.
      Advanced nurse practitioners are ideally positioned to act as leaders both within
      and beyond the health care organisation. EVALUATION: From the available research
      evidence, several support structures and mechanisms are identified as enablers
      for advanced nurse practitioners to enact their leadership role. CONCLUSION:
      Health care organisations need to include building leadership capacity as a
      priority in their strategic plan and take action to build-up the level of
      advanced nurse practitioner leadership. IMPLICATIONS FOR NURSING MANAGEMENT:
      Nurse executives have a vital role in influencing the organisation's strategic
      plan and making a business case for prioritising leadership capacity building
      within advanced nurse practitioners. A challenge for nurse executives faced with
      competing service and leadership development demands, involves strategic decision
      making regarding whether the advanced nurse practitioner's role is limited to
      service delivery or its potential in leading health care reforms is realised.

PMID- 27873384
TI  - Attention allocation towards own face is pronounced during middle adolescence: an
      eye-tracking study.
AB  - Increased interest in the self has long been deemed to be one of the most
      peculiar characteristics of adolescence. On the basis of this, we conjectured
      that attentiveness towards self-relevant information, especially one's own face,
      becomes more pronounced during the middle adolescence. The present study tested
      this hypothesis by comparing the pattern of visuospatial attention allocation to
      their own face among early, middle and late adolescent males using an eye
      tracking methodology. The results have shown a clear pattern of increased
      attention allocation towards their own face over a close friend's and a
      stranger's face in middle adolescents, but fixation durations on their own and a
      friend's face did not differ from each other in early and late adolescents. In
      addition, middle adolescents showed higher public self-consciousness and a lower
      level of self-esteem than early and late adolescents, respectively. These results
      indicate that attention allocation towards one's own face is more pronounced
      during middle adolescence, and is associated with increased interest in their own
      attributes.

PMID- 27873385
TI  - Introgression and selection shaped the evolutionary history of sympatric sister
      species of coral reef fishes (genus: Haemulon).
AB  - Closely related marine species with large overlapping ranges provide
      opportunities to study mechanisms of speciation, particularly when there is
      evidence of gene flow between such lineages. Here, we focus on a case of
      hybridization between the sympatric sister-species Haemulon maculicauda and H.
      flaviguttatum, using Sanger sequencing of mitochondrial and nuclear loci, as well
      as 2422 single nucleotide polymorphisms (SNPs) obtained via restriction site
      associated DNA sequencing (RADSeq). Mitochondrial markers revealed a shared
      haplotype for COI and low divergence for CytB and CR between the sister-species.
      On the other hand, complete lineage sorting was observed at the nuclear loci and
      most of the SNPs. Under neutral expectations, the smaller effective population
      size of mtDNA should lead to fixation of mutations faster than nDNA. Thus, these
      results suggest that hybridization in the recent past (0.174-0.263 Ma) led to
      introgression of the mtDNA, with little effect on the nuclear genome. Analyses of
      the SNP data revealed 28 loci potentially under divergent selection between the
      two species. The combination of mtDNA introgression and limited nuclear DNA
      introgression provides a mechanism for the evolution of independent lineages
      despite recurrent hybridization events. This study adds to the growing body of
      research that exemplifies how genetic divergence can be maintained in the
      presence of gene flow between closely related species.

PMID- 27873386
TI  - Identification of multiple sclerosis patients at highest risk of cognitive
      impairment using an integrated brain magnetic resonance imaging assessment
      approach.
AB  - BACKGROUND AND PURPOSE: While impaired cognitive performance is common in
      multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic
      resonance imaging (MRI) screening algorithm is proposed to identify patients at
      highest risk of cognitive impairment. The objective was to examine whether
      assessment of lesion burden together with whole brain atrophy on MRI improves our
      ability to identify cognitively impaired MS patients. METHODS: Of the 1253
      patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI
      and clinical data available were included in the analysis. Brain MRI and
      neuropsychological assessment with the Brief International Cognitive Assessment
      for Multiple Sclerosis were performed. Multivariable logistic regression and
      individual prediction analysis were used to investigate the associations between
      MRI markers and cognitive impairment. The results of the primary analysis were
      validated at two subsequent time points (months 12 and 24). RESULTS: The
      prevalence of cognitive impairment was greater in patients with low brain
      parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml)
      than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds
      ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified
      in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82%
      negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of
      confirmed cognitive decline over the follow-up was greater in patients with high
      T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7). CONCLUSIONS:
      The integrated MRI assessment of lesion burden and brain atrophy may improve the
      stratification of MS patients who may benefit from cognitive assessment.

PMID- 27873387
TI  - Physical exercise remodels visceral adipose tissue and mitochondrial lipid
      metabolism in rats fed a high-fat diet.
AB  - We aimed to investigate the effects of two physical exercise models, voluntary
      physical activity (VPA) and endurance training (ET) as preventive and therapeutic
      strategies, respectively, on lipid accumulation regulators and mitochondrial
      content in VAT of rats fed a high-fat diet (HFD). Sprague-Dawley rats (6 weeks
      old, n=60) were assigned into sedentary and VPA groups fed isoenergetic diets:
      standard (S, 35 kcal% fat) or HFD (71 kcal% fat). The VPA groups had free access
      to wheel running during the entire protocol. After 9 weeks, half of the sedentary
      animals were exercised on a treadmill while maintaining the dietary treatments.
      The HFD induced no changes in plasma non-esterified fatty acids (NEFA) and
      glycerol levels and decreased oxidative phosphorylation (OXPHOS) subunit IV and
      increased truncated/full-length sterol regulatory element-binding transcription
      factor 1c (SREBP1c) ratio in epididymal white adipose tissue (eWAT). VPA
      decreased plasma glycerol levels, aquaglyceroporin 7 (AQP7) and increased subunit
      I of cytochrome c oxidase (COX) protein, in standard diet fed animals. Eight
      weeks of ET decreased body weight, visceral adiposity and adipocyte size and
      plasma NEFA and glycerol levels, as well as AQP7 protein expression in eWAT. ET
      increased fatty acid translocase (FAT/CD36), mitochondrial content of complexes
      IV and V subunits, mitochondrial biogenesis and dynamic (mitofusins and optic
      atrophy 1)-related proteins. Moreover, lipogenesis-related markers (SREBP1c and
      acetyl CoA carboxylase) were reduced after 8 weeks of ET. In conclusion, ET
      induced alterations reflect a positive effect on mitochondrial function and the
      overall VAT metabolism of HFD-induced obese rats.

PMID- 27873389
TI  - Sildenafil, unbridled optimism, and heart failure with preserved ejection
      fraction.

PMID- 27873388
TI  - Effects of sildenafil on cardiac structure and function, cardiopulmonary exercise
      testing and health-related quality of life measures in heart failure patients
      with preserved ejection fraction and pulmonary hypertension.
AB  - AIMS: We recently showed that sildenafil did not improve pulmonary pressures and
      exercise capacity in a cohort of patients with heart failure and preserved
      ejection fraction (HFpEF) and predominantly postcapillary pulmonary hypertension.
      Here, we present the effects of sildenafil on cardiac structure and function,
      cardiopulmonary exercise testing, laboratory parameters and health-related
      quality of life measures. METHODS AND RESULTS: Fifty-two HFpEF patients with
      pulmonary hypertension (mean pulmonary artery pressure >25 mmHg; pulmonary artery
      wedge pressure >15 mmHg) were randomized to sildenafil 60 mg three times a day or
      placebo and treated for 12 weeks. Sildenafil neither changed cardiac structure
      nor function on echocardiography compared with placebo. Considering all patients
      irrespective of maximal effort, sildenafil reduced peak heart rate by 8 b.p.m.
      [95% confidence interval (CI) -14.97 to -1.03] and peak blood pressure by 13.8
      mmHg (95% CI -22.04 to -5.47)/7.3 mmHg (95% CI -13.60 to -1.07) (both P < 0.05
      vs. placebo). The minute ventilation/carbon dioxide production (VE/VCO2 ) slope
      remained unchanged in the sildenafil group (0.3, 95% CI -1.37-1.98), while it was
      reduced in the placebo group (-7.6, 95% CI -12.97 to -2.25, P = 0.002). In both
      groups, renal function improved and N-terminal pro-brain natriuretic peptide
      concentration reduced equally. Haemoglobin and glycated haemoglobin levels
      slightly decreased in the sildenafil group (P < 0.05 vs. placebo). All domains of
      the Kansas City Cardiomyopathy Questionnaire increased during treatment, but no
      differences between sildenafil and placebo were found. CONCLUSION: Treatment with
      sildenafil for 12 weeks in patients with HFpEF and predominantly isolated
      postcapillary pulmonary hypertension did not affect cardiac structure and
      function, integrative exercise responses, laboratory parameters, and/or quality
      of life. Clinicaltrials.gov number NCT01726049.

PMID- 27873393
TI  - Tributes to Peter Alan Trott, MB BChir FRCPath.

PMID- 27873391
TI  - Immunocytochemical staining for p53 and Ki-67 helps to characterise urothelial
      cells in urine cytology.
AB  - OBJECTIVE: The presence of atypical cells in urine cytology is unsatisfactory for
      both cytologists and clinicians. The objective of this study was to test whether
      p53 and Ki-67 immunostaining could improve urothelial carcinoma (UC) detection on
      urinary cytology. METHODS: A total of 196 urine samples were analysed, 142 from
      the bladder, 41 from the upper tract and 13 from ileal bladder replacement.
      Cytology results were expressed as normal (N) (n = 81), atypia cannot exclude low
      grade UC (ALG) (n = 25), suspicious for high-grade UC (SHG) (n = 39) and high
      grade UC (HG) (n = 51). Actual diagnoses were confirmed by histopathological
      analysis, cystoscopic examination or follow-up for at least 1 year.
      Immunocytochemistry performed on CytoSpinTM slides allowed the determination of
      the percentage of positive cells with p53 and Ki-67. RESULTS: The median
      percentage values [first to third quartile] of p53 and Ki-67 were 0 [0-5] and 0
      [0-1] for N cytology, 5 [0-40] and 2 [1-10] for ALG, 10 [0-30] and 6 [3-25] for
      SHG, and 30 [10-80] and 20 [10-30] for HG, respectively. Statistically higher
      values were observed for both tests (P < 0.001) in positive cytologies (ALG, SHG
      and HG). The optimal cut-offs were 5% for p53 and 3% for Ki-67. The sensitivity
      and specificity for the detection of all UC were 86.4% and 76.7% for cytology
      alone, 81.3% and 93.2% for cytology and p53, 75.7% and 88% for cytology and Ki
      67, and 68.9% and 97.5% for cytology, p53 and Ki-67, respectively. CONCLUSION:
      Using p53 and/or Ki-67 in addition to cytology increases the specificity without
      penalising the sensitivity.

PMID- 27873390
TI  - Analysis of multiple primary cancer autopsy cases associated with breast cancer:
      2002-2010.
AB  - Breast cancer patients have a generally increased risk of developing second
      cancers. The object of this study was to clarify the increased as well as
      decreased incidence of cancers in breast cancer patients using autopsy cases. 164
      211 autopsy cases in the Annual of Pathological Autopsy Cases in Japan from 2002
      to 2010 were analyzed for multiple primary cancer (MPC). Female MPC cases (4222
      cases) were selected. We investigated the cancer incidence observed in breast
      cancer associated MPC. The Chi-squared test was used for analysis. All P-values
      were two-sided, and differences at P < 0.05 were considered significant. Breast
      cancer associated MPC showed a significantly increased incidence of ovarian,
      pancreatic, and skin cancer (Odds Ratio [95 % confidence interval (CI)]) = 1.464
      [1.03, 2.08], 1.414 [1.08, 1.85] and 2.092 [1.28, 3.41]), and a decreased
      incidence of colorectal and cervical cancer (OR [95 % CI]) = 0.732 [0.60, 0.90],
      0.605 [0.38, 0.96]). Our findings of an increased incidence of malignancies in
      breast cancer associated MPC cases were consistent with the results of previous
      population-based studies. This study is the first study to analyze massive
      autopsy data on MPC which provide new evidence clinically and pathologically.

PMID- 27873396
TI  - Education is the basis for the future of Dermato-Venerology.

PMID- 27873395
TI  - N-Heterocyclic Carbene Catalyzed gamma-Dihalomethylenation of Enals by Single
      Electron Transfer.
AB  - An N-heterocyclic carbene (NHC) catalyzed dihalomethylenation of enals is
      described. It is a rare example of merging NHC catalysis with single-electron
      chemistry, a challenging topic with limited previous success. The versatile
      carbon-centered trihalomethyl radicals have been demonstrated, for the first
      time, to be compatible with an NHC-bound intermediate, thus leading to efficient
      and regioselective intermolecular C-C bond formation. The mild process provides
      straightforward access to unsaturated delta,delta-dihalo esters.

PMID- 27873397
TI  - Reviewers who have performed more than three reviews in 2016 Thank you so much!

PMID- 27873400
TI  - The Reject.

PMID- 27873398
TI  - From the coliseum to the convention centre: a reflection on the current state of
      medical education conferences and conference-goers.
AB  - The advancement of knowledge and development of policy in the field of medical
      education require critical academic discourse among the most intelligent medical
      educators; and critical academic discourse requires coffee. In this essay, we
      reflect on the state of professional development conferences in the field of
      medical education and the rituals that surround their success. Having begun in
      ancient Greece, symposia were ripe with debauchery. Today, sedated by the light
      brown walls of hotel conference centres, symposia are more serious endeavours,
      engaging men and women in the sometimes turbulent waters of epistemological
      debate. The abstract submission process (summed up by: 'Yay! It was accepted for
      presentation' [Deep breath] 'Oh no...it was accepted for presentation'), the
      'juggling act' of parent attendees, the acting prowess of abstract presenters and
      the unapologetic approach to buffet eating are all by-products of the collision
      of true intellects among medical education scholars. We hold these rituals in
      high regard and argue that they are required to advance the field of medical
      education. These rituals bind the walls supporting true progressive thought and
      innovative research, all fuelled by the glass of wine purchased with that one
      coveted drink ticket.

PMID- 27873401
TI  - Simplifying education scholarship: new format requirements for publication
      success.

PMID- 27873402
TI  - Cosmologies of selection: lessons from the faculty biscuit tin.
AB  - We conducted an ethnography of the faculty biscuit tin as we were interested in
      the lived experience of the biscuits contained within it. We used a
      constructivist epistemology, a social constructionist interpretive framework and
      a phenomenological methodology that included analysis from the perspectives of
      deixis and cosmology. The biscuits perceived that they were important to a
      selecting force and that the characteristics of one particular group had a
      specific value to the selector. Some enduring benefits may derive from the
      selection of this group, although its attractions were less immediately obvious
      than those of others. What is immediately attractive may not be the most fit for
      purpose; lessons for the selection of medical students may arise from this
      exploration of the selection experiences of biscuits in a faculty biscuit tin.

PMID- 27873403
TI  - Does your pig go 'knor'? Medical students' skills in using animal sounds as a
      cross-cultural paediatric engagement tool.
AB  - The development of verbal communication skills is an important aspect of medical
      education as accurate assessment in part relies on effectively obtaining
      information from patients. When assessing children of different cultural or
      ethnic backgrounds, young medics may find effective verbal communication
      difficult because they lack understanding about what children are really like.
      Animal noises are a likely tool with which to successfully engage with young
      children. However, these differ by culture and it is unclear whether young New
      Zealand medical students will be adept at effectively engaging and communicating
      with foreign children via this mode of communication. We therefore assessed
      whether medical students in our country were able to accurately reproduce animal
      noises from different cultures. Six current medical students from New Zealand
      (with English as their first language) were assessed on their ability to
      reproduce animal noises from three different foreign languages: Dutch, Arabic and
      Danish. The animals selected were duck, cow, dog, frog, pig and sheep. Students
      were played recordings of the foreign-language animal noises, and were then rated
      on a scale of 1-5 (1 = poor, 5 = outstanding) on their ability to reproduce the
      noise. Arabic animal noises were reproduced more convincingly than those in the
      other languages (mean score: 3.8), of which animal noises in Danish were worst
      (mean score: 3.1). Perhaps unsurprisingly, sheep noises were reproduced best
      (mean score: 4.7), whereas pig noises were the least convincing (mean score:
      2.2). Findings indicate that New Zealand medical students are likely to be better
      than average at reproducing animal noises in the languages examined, and are
      perhaps socially and genetically predisposed to replicating sheep noises
      successfully. They are therefore likely to make good paediatric registrars and
      fabulous au pairs. The study highlights the more serious issues of multicultural
      understanding and tolerance of other cultures, and provides a novel paediatric
      engagement tool for those young medics who do not really 'get' children.

PMID- 27873404
TI  - The show must go on? Patients, props and pedagogy in the theatre of the OSCE.
AB  - According to Shakespeare, all the world's a stage, and all the men and women
      merely players. The objective structured clinical examination (OSCE), that most
      ubiquitous form of assessment in health professions education, offers us a
      particular instance of this maxim. Comprising at first glance a world of
      psychometric data, detailed checklists and global rating scales, the OSCE sets
      out to facilitate the assessment of a candidate's competence in a highly
      standardised and objective fashion. Despite this clear intention, OSCEs also
      offer a rich vein of (often unacknowledged) social and cultural processes. In
      this commentary, we draw on Goffman's dramaturgy metaphor and our experiences to
      undertake a wry examination of some of the least intended consequences of OSCEs.
      We take a satirical look at both the potential impact on patients and the
      pedagogical implications of this form of assessment. We now urge you to sit back,
      settle in and enjoy the show, as we raise the curtain on this one-night-only
      performance!

PMID- 27873405
TI  - The 10 most wanted test cheaters in medical education.
AB  - This paper takes on a list of the 10 most wanted test cheaters comparable with
      'most wanted' lists used by law enforcement agencies to bring attention to the
      issue of test cheating in medical education. The research provides an overview of
      test cheating in modern medical education, presents a typology of common
      cheaters, and provides guidelines for the prevention and detection of cheating.

PMID- 27873406
TI  - WATCH Scrubs: a video observational study of workplace-based learning at Sacred
      Heart Hospital.
AB  - CONTEXT: Workplace-based learning remains the cornerstone of clinical training.
      Teaching in the clinical environment promotes active engagement as trainees are
      required to combine their competencies (e.g. skills in history taking,
      examination and clinical reasoning) to determine an appropriate course of action.
      High-quality clinical teaching supports and scaffolds trainees' learning in
      clinical workplaces. OBJECTIVES: This study aimed to explore the quality of
      clinical teaching at a large teaching hospital. METHODS: A retrospective video
      observational study of 9 years of workplace-based learning at Sacred Heart
      Hospital, a large private teaching hospital, was conducted. Each academic year
      was observed by one researcher. Clinical teaching encounters were identified and
      analysed using the Warwick Assessment insTrument for Clinical teacHing (WATCH).
      Descriptive observation notes were recorded and analysed thematically. RESULTS: A
      total of 131 teaching encounters provided by 12 tutors were identified. The 15
      item instrument demonstrated a Cronbach's alpha of 0.89. The hidden curriculum,
      role modelling and reflection played prominent roles in trainees' personal and
      professional development. CONCLUSIONS: Trainees' learning in clinical workplaces
      extends beyond the formal teaching they receive to include the development of
      professional behaviours through role modelling and reflection on clinical
      encounters.

PMID- 27873407
TI  - Discussing discursive discussions.
AB  - Discussions are an important part of medical education research papers, but there
      is little guidance on how to write up the discussion section. A good discussion
      section should relate closely to the results; it should include a balanced review
      of the strengths and weaknesses of the study; it should be realistic in
      evaluating the applicability of the results; and it should mention the
      feasibility of widespread adoption of the intervention. This paper describes a
      review of the discussion sections of research papers published in Medical
      Education. The review led to further discussion. Common errors in writing
      discussion sections include: minimising the weaknesses of a study or exaggerating
      its strengths; closing down debate too early or opening up new arguments at too
      late a stage; and getting carried away by the potential of technology or getting
      very carried away by the potential of technology. Some discussions can be too
      long, but restricted word counts keep abstracts mercifully short.

PMID- 27873408
TI  - Number needed to eat: pizza and resident conference attendance.
AB  - The didactic conference is a common part of the resident education curriculum.
      Given the demands of clinical responsibilities and restrictions on duty hours,
      maximising education is a challenge faced by all residency programmes. To date,
      little research exists with respect to how the provision of complimentary food
      affects physician and resident conference attendance. The objective of this study
      was to determine whether complimentary food improves resident arrival times and
      attendance at educational conferences and, furthermore, to test whether this
      provision is a potentially cost-effective tool for improving education. A
      retrospective review of 36 resident educational Friday noon conferences,
      including 1043 resident arrivals, was performed. Data were analysed for total
      attendance, arrival times, number needed to eat (NNE) and the percentage of
      residents arriving on time, and compared between days on which food was and was
      not provided. Median attendance was 3.7% higher (p = 0.04) on days on which food
      was provided, at a cost of US$46 for each additional resident in attendance.
      Arrival times were also statistically significantly improved when food was
      provided, with a median improvement of 0.7 minutes (p = 0.02) and an 11.0%
      increase in on-time arrivals (p < 0.001). The NNE was 10.6. Complimentary food
      improves both attendance and arrival times by a small, but statistically
      significant, degree. The provision of complimentary food can be considered as an
      incentive for attendance and on-time arrival at didactic educational sessions,
      although more cost-effective modalities may exist.

PMID- 27873409
TI  - Is the long case dead? 'Uh, I don't think so': the Uh/Um Index.
AB  - Current tools for clinical assessment are tedious and time-consuming,
      particularly the dreadful long case. There is a need for novel instruments that
      incorporate other aspects of competence. We propose such a method, namely the
      Uh/Um Index. Our innovation paper describes the rationale for using speech
      dysfluency and occurrences of filler words such as 'uh' and 'um' as a proxy for
      competence. This appears to have won initial support from senior clinicians in
      our institution. Additional research is needed (non-restricted grants are
      welcomed) to establish rigorous standard setting and to fund our attendance at
      overseas conferences to make the Uh/Um Index the new buzzword in medical
      education.

PMID- 27873410
TI  - Where do physicians start and end?
AB  - Medical education is primarily about training physicians and maintaining their
      capabilities over time. Given that physicians are the primary focus of the field,
      there is a need for a clear idea of what physicians are or could be. This paper
      seeks to explore this issue by posing the simple question: ?Where do physicians
      start and end?' In doing so, the authors explore a series of different conceptual
      frames, including those of a physician's physical dimensions, their cellular
      boundaries, personal intentions and beliefs, professional identity, regulation,
      entrustability, professional performance, extended cognition, and disability.
      This existential look at the concept of a physician demonstrates the plurality of
      medical education scholarship and the implications of the many intersecting
      points of view in the field.

PMID- 27873411
TI  - Training physicians for the real world of medicine: administration-based
      learning.
AB  - Tired of outdated teaching formats like case-based learning (CBL), problem-based
      learning (PBL) and team-based learning (TBL)? We wanted something fresh for our
      medical school, something that would prepare our graduates for the modern
      practice of medicine, something that would satisfy regulatory agencies and our
      deans. After doing an extensive needs assessment, which we ignored, we decided to
      replace basic science in our curriculum with something more practical:
      administration-based learning (ABL). We taught students how to fix fax machines,
      how to deal with angry team members, and how to maximise revenue in private
      practice - lessons that were well received and were more consistent with what
      physicians really need to learn to be effective practitioners. Educational
      outcomes have been positive, and although more research is needed, we call on
      other schools to add ABL tracks to their own curricula.

PMID- 27873412
TI  - What's in a name? Word inflation, punctuation, abbreviation and cloud formation.
AB  - The title of a journal paper offers a crucial portal into any scientific field.
      It determines whether interested readers locate the paper and whether others have
      enough interest sparked to lead them to read the abstract. This article looks at
      authored journal paper titles in Medical Education over its first 50 years (n =
      6357) of publication and Medical Teacher over its first 35 years of publication,
      revealing both trends in areas of interest and how those interests are worded.
      Word clouds per decade showed a shift from teaching to learning and from
      examination to assessment, and new foci on learning, patients, research and
      feedback in both journals. The average length of title in Medical Education
      peeked in the 2000s, dropping to 70 characters in the 2010s, with no titles being
      longer than 140 characters (the length of a tweet) in this last decade.
      Abbreviations were used sparingly. The use of humorous titles, although not
      common, has increased in recent years. The use of the colon showed a marked
      increase in the 1980s, dropping a little in the 2000s but resurging in the 2010s.
      Titles posed as a question increased steadily, appearing to plateau in the 2000s
      at 11%. The use of humour and questions suggests that the authors of these
      articles are submitting papers to be selected by the human rather than just the
      virtual eye. We also hypothesise that the use of humour may indicate a maturation
      of medical education as a subject.

PMID- 27873413
TI  - Six degrees of separation: the small world of medical education.
AB  - CONTEXT: Conventional wisdom has it that everyone on earth is on average only six
      steps away from knowing any other person through 'a friend of a friend'. On a
      local level, however, many people experience that most of their acquaintances
      know each other. It is thus hard to imagine how such a highly clustered group
      could be so well connected to the rest of the world. In this paper, we
      investigate how co-authorship connects scholars in medical education and whether
      the six degrees of separation hypothesis also applies to the network of authors
      in the field. METHODS: We constructed a mathematical graph from publication data
      obtained on the top three journals in the field and analysed it using social
      network analysis methods. We found Lorelei Lingard to be one centre of the
      network of co-authors and determined the numbers of authors who were one, two or
      more steps away from her. We further created a website that makes it possible to
      identify the shortest path from any author in the field to any other, including
      links to the connecting papers. RESULTS: The analysis covered 16 653 papers by a
      total of 24 258 different authors. Co-authorship connected authors into 68 663
      unique pairs, of which 61 937 had co-authored only one article; 67.43% of all
      authors were linked to each other through a 'co-author of a co-author'. The
      average shortest path between any two authors in this network was 5.98 (min 1,
      max 17); the average distance to Lorelei Lingard was 4.17 (min 1, max 10).
      CONCLUSION: The field of medical education represents what social network
      analysts term 'a small world network'. Making the connections between its actors
      visible may provide a new perspective on social phenomena that occur in this
      world, including peer review, citation and conference invitations.

PMID- 27873414
TI  - Virtual sorting hatTM technology for the matching of candidates to residency
      training programs.
AB  - BACKGROUND: The matching of medical students and trainees to appropriate training
      programmes poses many challenges, including financial cost and applicant stress.
      There are few studies that have examined alternatives to the current process of
      matching candidates to specialist training. Case reports from Hogwarts School of
      Witchcraft and WizardryTM have suggested that wearable technology may be used to
      assign individuals with particular sets of skills and virtues to an appropriate
      house. METHODS: Investigators developed a modified sorting hat in the form of an
      online, cross-sectional survey. The virtual sorting hat was delivered to medical
      students at the National University of Ireland, Galway, and medical practitioners
      practising in the associated hospitals and communities. Pearson's chi-square was
      used to demonstrate correlations between the allocation of participants to
      Hogwarts' houses by virtual sorting hat technology and expressed higher
      specialist training preference. RESULTS: Virtual sorting hat technology, applied
      to medical undergraduates and postgraduates, allocated most participants to
      HufflepuffTM (44%) and RavenclawTM (32%). Allocation to Gryffindor was associated
      with preference for surgery and allocation to SlytherinTM with preference for
      psychiatry. CONCLUSION: Virtual sorting hat technology requires significant
      refinement before application to medical mugglesTM .

PMID- 27873415
TI  - Through the looking glass: a different lens on medical education.

PMID- 27873416
TI  - The unsuccessful treatment of a case of 'Writer's Block': a replication in
      medical education.

PMID- 27873417
TI  - The clinic is my woodshed: a new paradigm for learning and refining communication
      skills.
AB  - Jazz cats use the term 'woodshedding' to denote a period of intense practice
      during which they aim to take their playing up a few notches. Developing
      expertise, whether we are speaking musically or talking about communicating with
      patients, requires a lifelong commitment to such practice. For physicians, the
      woodshed is not a practice room or an isolated space. No: clinical environments
      are the woodsheds; they are the only places in which one can hone communication
      skills. The idea of 'shedding' in the setting of routine practice challenges
      prevailing notions about communication skills training and has implications for
      how such skills should be learned, nurtured and assessed. In this essay, we use
      stories of woodshedding from jazz music history to discuss concepts related to
      deliberative practice, formal education and learning communities.

PMID- 27873418
TI  - Learning the hard way: 10 lessons for developing undergraduate curricula.
AB  - The present study outlines key learning points derived from 2 years spent
      developing a national undergraduate curriculum for child health. Findings are
      sourced from analyses of a series of semi-structured musings by beleaguered
      educationalists and may serve to reassure others engaged in developing
      undergraduate curricula that it is possible to survive the process and even to
      produce something quite good. The authors' best advice is to do it, but don't say
      we didn't warn you.

PMID- 27873419
TI  - Post-call delirium.
AB  - Although frequently diagnosed in hospital in-patients, delirium is often
      recognised but under-reported in the housestaff population. It is estimated that
      more than 90% of housestaff will experience regular episodes of post-call
      delirium. This paper identifies diagnostic criteria and discusses approaches to
      treatment.

PMID- 27873420
TI  - And you try and tell the medical students of today that... and they won't believe
      ya.
AB  - Older clinicians typically engage in reflections on their own early careers and
      indeed whichever generation of clinician you talk to, their medical school and
      early career experiences were more challenging than the last. We draw on
      inspiration from Monty Python and specifically the Four Yorkshiremen to
      illustrate this point. However, as we strive to lay the foundations of learning
      that avoids the adage 'whatever doesn't kill you, makes you stronger', we must
      remember that medics are competitive... even at complaining.

PMID- 27873421
TI  - A fresh look at Miller's pyramid: assessment at the 'Is' and 'Do' levels.
AB  - In its silver jubilee, we celebrate the ground-breaking pyramid of George Miller
      by submitting a fresh look at it. We discuss two questions. (i) Does the
      classical pyramidal structure perfectly portray the relationships of the four
      levels that were described by Miller? (ii) Can the model of Miller fulfill the
      unmet needs of assessors to measure evolving essential constructs and accommodate
      the increasingly sophisticated practice of assessment of health professionals? In
      response to the first question, Miller's pyramid is revisited in view of two
      assumptions for pyramidal structures, namely: hierarchy and tapering. Then we
      suggest different configurations for the same classical four levels and indicate
      when to use each one. With regard to the second question, we provide a rationale
      for amending the pyramid with two further dimensions to assess personal qualities
      of students at the 'Is' level and their performance in teams at the 'Do'
      (together) level. At the end of the article, we yearn to think outside the
      pyramid and suggest the Assessment Orbits framework to assess students as
      individuals and in teams. The five Assessment Orbits alert educators to assess
      the emerging cognitive and non-cognitive constructs, without implying features
      such as hierarchy or tapering that are ingrained in pyramidal structures. The
      'Is' orbit attends to the personal qualities of graduates 'who' we may (or may
      not) trust to be our physicians. Assessment of teams at the 'Do' level (together)
      offers a paradigm shift in assessment from competitive ranking (storming) among
      students toward norming and performing as teams.

PMID- 27873423
TI  - The power of the pen: how to make physicians more friendly and patients more
      attractive.
AB  - CONTEXT: Studies have shown that patients' subjective perceptions of physicians'
      competence and friendliness are relevant aspects of a successful treatment,
      influencing patients' well-being and trust in the physician. Psychological
      research has repeatedly shown that unconsciously contracting muscles that are
      usually used to smile can intensify and even elicit positive feelings (known as
      facial feedback). Empirical evidence also suggests that a smiling person is
      favourably judged by others with respect to attractiveness and trustworthiness.
      AIM: This study's purpose was to investigate how an induced muscle contraction,
      similar to that of a smile, affects physicians' interactions with a standardised
      patient. It was expected that the 'smile intervention' would affect physicians'
      and patients' perceptions, resulting in higher ratings of the friendliness and
      attractiveness of physicians in the intervention group. METHODS: Twenty
      physicians participated in the randomised controlled study (10 male, 10 female).
      Physicians were randomly assigned to one of two conditions: an intervention group
      (performing an easy cognitive task while smiling; n = 11) or a control group
      (performing an easy cognitive task without smiling; n = 9). Afterwards,
      physicians had a 5-minute consultation with a standardised patient. This
      consultation was subsequently rated by physicians, the patient and an external
      rater using 10-point Likert scales. RESULTS: Physicians in the intervention group
      were rated as significantly friendlier by the external rater (mean 7.81 versus
      7.11; p = 0.097, eta2  = 0.15). In addition, physicians in the intervention group
      rated the patient as significantly more attractive (mean 6.91 versus 4.78; p =
      0.017; eta2  = 0.28). CONCLUSIONS: Our results suggest that physicians can
      influence their friendliness and their perception of patients' attractiveness.
      Thereby the 'power of pen' can be an efficient method for making the hospital a
      friendlier place.

PMID- 27873424
TI  - The Cross-Canada Quintet presents variations on music: movements in the keys of
      H, P and E.
AB  - Whether it is rock playing in the background during a surgery, cool jazz that
      wafts from our office computer speakers as we write up our clinical notes, or the
      soaring of a symphony on the radio that inspires that perfect flourish to an
      article, music is woven throughout much of our clinical and academic lives. For
      the five of us, however, music alternates between the background and foreground
      in our lives as health professions educators. Music balances the working day,
      illuminates our research, and reconciles the utility of our training with the
      originality of our practice. We invite you to discover the interplays,
      dissonances and harmonies inspired by and reflected in this leitmotif. Pull up a
      chair, sit back, put on one of your own favourite pieces and explore these ideas
      as we riff and rhapsodise on variations on this theme.

PMID- 27873426
TI  - Developing a pragmatic medical curriculum for the 21st century.
AB  - Medical education within a hospital setting presents both opportunities and
      challenges. The range of educational experiences on offer is often vast, though
      may be lost in the overworked and convoluted environment of a tertiary centre. As
      our learners are increasingly consumed by the literal and figurative labyrinths
      of hospitals and electronic learning logs, are we failing to train them in the
      skills they need to deliver 21st century health care? In response to this problem
      we propose a FARCICAL approach: Fostering A Relevant Curriculum that Is Closer to
      Actual Life.

PMID- 27873425
TI  - I want you to pretend to be sincere.
AB  - Medical education has changed dramatically since the inception of this journal 50
      years ago and is indeed a work in progress: there is now heavy emphasis on the
      character of the physician, in particular, and professionalism, in general. The
      subjects of communications skills and the teaching of sincerity, empathy and
      compassion are relative newcomers to the stage: they are not even as old as this
      journal itself. Nevertheless, these topics arose in an ancient debate dating from
      classical antiquity. 'Can we teach virtue?' Plato wondered in the Meno. Not
      exactly, he concluded. Aristotle believed that acquirement of the virtues enables
      one to attain the human good, which, in turn, spills over to any profession in
      which the human being decides to engage. Aristotle, along with his successor,
      Thomas Aquinas, the 13th century philosopher, argued that the virtues cannot be
      taught but only acquired, with practice and time, in the real situation.

PMID- 27873427
TI  - Magnetically Induced Continuous CO2 Hydrogenation Using Composite Iron Carbide
      Nanoparticles of Exceptionally High Heating Power.
AB  - The use of magnetic nanoparticles to convert electromagnetic energy into heat is
      known to be a key strategy for numerous biomedical applications but is also an
      approach of growing interest in the field of catalysis. The heating efficiency of
      magnetic nanoparticles is limited by the poor magnetic properties of most of
      them. Here we show that the new generation of iron carbide nanoparticles of
      controlled size and with over 80 % crystalline Fe2.2 C leads to exceptional
      heating properties, which are much better than the heating properties of
      currently available nanoparticles. Associated to catalytic metals (Ni, Ru), iron
      carbide nanoparticles submitted to magnetic excitation very efficiently catalyze
      CO2 hydrogenation in a dedicated continuous-flow reactor. Hence, we demonstrate
      that the concept of magnetically induced heterogeneous catalysis can be
      successfully applied to methanation of CO2 and represents an approach of
      strategic interest in the context of intermittent energy storage and CO2
      recovery.

PMID- 27873429
TI  - Low association between fasting and OGTT stimulated glucose levels with HbA1c in
      overweight children and adolescents.
AB  - BACKGROUND: Diabetes and prediabetes are defined based on different methods such
      as fasting glucose, glucose at 2-hour in oral glucose tolerance test (OGTT), and
      glycated hemoglobin A1c (HbA1c). These parameters probably describe different
      deteriorations in glucose metabolism limiting the exchange between each other in
      definitions of diabetes. OBJECTIVE: To investigate the relationship between OGTT
      and HbA1c in overweight and obese children and adolescents living in Germany.
      METHODS: Study population: Overweight and obese children and adolescents (n =
      4848; 2668 female) aged 7 to 17 years without known diabetes. The study
      population was stratified into the following subgroups: normal glucose tolerance,
      prediabetes, diabetes according to OGTT and/or HbA1c categories, confirmed
      diagnosis of diabetes. RESULTS: In the entire study group fasting plasma glucose
      (FPG) correlated weakly to 2-hour glucose (r = 0.26), FPG correlated weakly to
      HbA1c (r = 0.18), and 2-hour glucose correlated weakly to HbA1c (r = 0.17, all P
      < .001). Patients with confirmed diabetes showed a very high correlation between
      FPG and 2-hour glucose (r = 0.73, n = 50). Moderate correlations could be found
      for patients with impaired fasting glucose (2-hour glucose vs HbA1c: r = 0.30, n
      = 436), for patients with diabetes according to OGTT and/or HbA1c (FPG vs 2-hour
      glucose: r = 0.43; 2-hour glucose vs HbA1c: r = -0.30, n = 115) and for patients
      with confirmed diabetes (2-hour glucose vs HbA1c: r = -0.47, all P < .001).
      CONCLUSIONS: Because FPG, 2-hour glucose, and HbA1c correlated only weakly we
      propose that these parameters, particularly in the normal range, might reflect
      distinct aspects of carbohydrate metabolism.

PMID- 27873430
TI  - Synthesis of Site-Specific Dye-Labeled Polymer via Atom Transfer Radical
      Polymerization (ATRP) for Quantitative Characterization of the Well-Defined
      Interchain Distance.
AB  - Novel difunctional initiators that incorporate Forster/fluorescence resonance
      energy transfer (FRET) pairs are generated to carry out atom transfer radical
      polymerization of styrene, methyl methacrylate, and n-butyl methacrylate monomers
      by an efficient manner. Based on the chemical structures of the initiators, the
      locations of the fluorophore moiety are dictated to be in the center of the chain
      with accurately quantified chain functionality (>90% labeling ratio). The site
      specific integration of FRET dyes into separate polymer chain centers allows for
      characterization of the well-defined interchain distance quantitatively based on
      the response between these fluorescent probes. The reliability of this technique
      is verified in bulk state, which is in well agreement with the theoretical ones.
      This well-defined FRET system is expected to be a promising candidate to provide
      a distinct physical image at a microscopic level regarding scaling chain
      dimension, chain interpenetration, and polymer compatibility.

PMID- 27873428
TI  - Data and Safety Monitoring Board evaluation and management of a renal adverse
      event signal in TOPCAT.
AB  - Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary
      obligation of ensuring study participant safety, while maintaining trial
      integrity. The role of DSMBs is expanding, and ideally should include post-hoc
      reporting of deliberative processes related to clinically important safety issues
      or factors that could impact on future trial designs. We describe how the TOPCAT
      DSMB detected, investigated, and adjudicated an unexpectedly large renal adverse
      event signal midway through the trial, and offer general guidelines for dealing
      with similar unanticipated occurrences in future trials. The detection of a
      greater than expected incidence of deterioration in renal function, occurring in
      6.1% of patients in the spironolactone arm compared with 3.9% in the placebo arm
      (P = 0.009), led to an in-depth DSMB review of associated study medication
      withdrawals and adverse events. The trial continued uninterrupted throughout the
      review, which reached the conclusions that spironolactone-associated renal
      dysfunction did not compromise overall patient safety or interfere with a
      perceived efficacy signal. Although no discrete mechanism for the spironolactone
      associated renal adverse event signal was identified, likely possibilities are
      discussed. In clinical trials, DSMBs and co-ordinating centres should have the
      resources to detect, investigate, and adjudicate unexpected safety issues, with
      goals of ensuring patient safety and preserving the potential for detection of
      therapeutic effectiveness. In TOPCAT, spironolactone-associated renal dysfunction
      emerged as a potentially trial-threatening adverse event and, although clinically
      important, did not lead to compromise of patient safety, trial interruption,
      termination, or apparent loss of treatment effectiveness.

PMID- 27873433
TI  - Blindness to background: an inbuilt bias for visual objects.
AB  - Sixty-eight 2- to 12-year-olds and 30 adults were shown colorful displays on a
      touchscreen monitor and trained to point to the location of a named color.
      Participants located targets near-perfectly when presented with four abutting
      colored patches. When presented with three colored patches on a colored
      background, toddlers failed to locate targets in the background. Eye tracking
      demonstrated that the effect was partially mediated by a tendency not to fixate
      the background. However, the effect was abolished when the targets were named as
      nouns, whilst the change to nouns had little impact on eye movement patterns. Our
      results imply a powerful, inbuilt tendency to attend to objects, which may slow
      the development of color concepts and acquisition of color words. A video
      abstract of this article can be viewed at: https://youtu.be/TKO1BPeAiOI.
      [Correction added on 27 January 2017, after first online publication: The video
      abstract link was added.].

PMID- 27873431
TI  - Hypoglycemia is common in children with cystic fibrosis and seen predominantly in
      females.
AB  - OBJECTIVE: To determine the prevalence of hypoglycemia in children and
      adolescents with cystic fibrosis (CF) in 2-hour oral glucose tolerance test
      (OGTT) and continuous glucose monitoring (CGM) under free-living conditions.
      RESEARCH DESIGN AND METHODS: Height, weight, body mass index (BMI), hemoglobin
      A1c (HbA1c), and Forced expiratory volume (FEV1%) were measured in children with
      CF (aged 5-18 years). Following OGTT, CGM was installed for 3 days. The total
      hypoglycemic and hyperglycemic time (%) during 3 days was measured. Subjects were
      categorized according to hypoglycemic time <3% (hypo -) and >=3% (hypo +). Each
      category was further divided according to hyperglycemic time <3% (hyper -) or
      >=3% (hyper +). RESULTS: OGTT and CGM were sequentially performed in 45 CF
      patients. The frequency of hypoglycemia in OGTT and hypoglycemic time ?3% of CGM
      were 13.3% and 27.5%, respectively. After 5 cystic fibrosis-related diabetes
      (CFRD) subjects were excluded, the number of subjects in each subgroup was 17
      (hypo-/hyper-), 12 (hypo-/hyper+), 6 (hypo+/hyper-), and 5 (hypo+/hyper+).
      Significantly higher insulin at 120 minutes was observed in OGTT in (hypo+/hyper
      ), as compared with subgroup (hypo-/hyper-) (P = .018). Total insulin levels were
      also significantly higher in (hypo+/hyper-), than (hypo-/hyper-), but were
      similar to those in the healthy control group (P = .049 and P = .076,
      respectively). There was a female predominance in hypoglycemic subjects both in
      OGTT and subgroup (hypo+/hyper-) in the CGM group (P = .033 and P = .033,
      respectively). FEV1 was significantly lower in hypo + group as a whole, and
      (hypo+/hyper+) subgroup than in (hypo-/hyper-), (P = .044 and P = .042,
      respectively); the difference was independent of body mass index-standard
      deviation score (BMI-SDS) (P = .15 and P = .12, respectively). CONCLUSION: The
      frequency of hypoglycemia in children with CF was higher in CGM than that in
      OGTT. Insulin secretion was delayed and total insulin levels increased in the
      hypoglycemic patients. Glucose instability/hypoglycemia is associated with poorer
      lung function in patients with CF, independent of nutritional status.

PMID- 27873434
TI  - Simple Copper Catalysts for the Aerobic Oxidation of Amines: Selectivity Control
      by the Counterion.
AB  - We describe the use of simple copper-salt catalysts in the selective aerobic
      oxidation of amines to nitriles or imines. These catalysts are marked by their
      exceptional efficiency, operate at ambient temperature and pressure, and allow
      the oxidation of amines without expensive ligands or additives. This study
      highlights the significant role counterions can play in controlling selectivity
      in catalytic aerobic oxidations.

PMID- 27873432
TI  - Low perinatal zinc status is not associated with the risk of type 1 diabetes in
      children.
AB  - AIM: Immunologic events during fetal life may play a part in the pathogenesis of
      type 1 diabetes (T1D). As zinc is involved in immunologic processes, the purpose
      was to investigate perinatal zinc status and the later risk of developing T1D and
      association to age at onset. METHODS: A population-based case-control study based
      on data from Danish Childhood Diabetes Register and the Danish Newborn Screening
      Biobank. Cases and controls were matched by birth year and month. Zinc status was
      analyzed in dried blood spots collected 5 to 7 days after birth. Logistic
      regression model was used to test the influence of zinc on risk of T1D. Linear
      regression modeling was used to examine the association between zinc status and
      covariates as well as age at onset. Zinc status was adjusted for HLA-DQB1
      genotype, birth data and maternal age. RESULTS: Each doubling in perinatal zinc
      status was not associated with T1D risk; odds ratio (OR) = 1.06 (95% confidence
      interval [CI] 0.84, 1.32) ( P  = 0.62), adjusted for birth year and season. This
      finding persisted after adjustment for possible confounders; OR = 1.01 (95% CI
      0.77, 1.34) ( P  = 0.93). In none of the cohorts there were significant
      associations to age at onset. CONCLUSION: The risk of developing T1D in Danish
      children was not associated with perinatal zinc status nor age at onset.

PMID- 27873435
TI  - Thiol-Ene Step-Growth as a Versatile Route to Functional Polymers.
AB  - A new use of the thiol-ene reaction to generate functional, redox-tunable
      polymers is described. To illustrate the versatility of this approach, tailored
      divinyl ether monomers were polymerized with triethylene glycol dithiol to yield
      polymers containing either a carbonate or zwitterionic phosphocholine within the
      polymer backbone. Similarly, dithioerythritol was polymerized with triethylene
      glycol divinyl ether to yield a polymer with pendant diols and show how
      functional groups can be designed into either the divinyl ether or dithiol
      monomer. Using the thioether functional group inherent to this polymerization,
      all three polymers were selectively and quantitatively oxidized to either
      sulfoxides or sulfones by treatment with dilute hydrogen peroxide or mCPBA,
      respectively. With these illustrative examples, it is shown that the thiol-ene
      polymerization is a broad-reaching method to access a class of new redox-active
      polymers which contain varied and dense functional-group compositions.

PMID- 27873437
TI  - Characterization and Crystal Structure of a Robust Cyclohexanone Monooxygenase.
AB  - Cyclohexanone monooxygenase (CHMO) is a promising biocatalyst for industrial
      reactions owing to its broad substrate spectrum and excellent regio-, chemo-, and
      enantioselectivity. However, the low stability of many Baeyer-Villiger
      monooxygenases is an obstacle for their exploitation in industry.
      Characterization and crystal structure determination of a robust CHMO from
      Thermocrispum municipale is reported. The enzyme efficiently converts a variety
      of aliphatic, aromatic, and cyclic ketones, as well as prochiral sulfides. A
      compact substrate-binding cavity explains its preference for small rather than
      bulky substrates. Small-scale conversions with either purified enzyme or whole
      cells demonstrated the remarkable properties of this newly discovered CHMO. The
      exceptional solvent tolerance and thermostability make the enzyme very attractive
      for biotechnology.

PMID- 27873438
TI  - Polysulfates [Sn O3n+1 ]2- : With the [S6 O19 ]2- Anion, has the End been
      Reached?
AB  - The S6 O192- ion was obtained both as rubidium and ammonium salt from the
      reaction of the respective sulfate with SO3 . It is the largest polysulfate ion
      known to date and exhibits a chain of six vertex-connected [SO4 ] tetrahedra. The
      unique compound was comprehensively characterized and the bonding within the
      anion was elucidated by theoretical investigations.

PMID- 27873439
TI  - Is stand-alone D-dimer testing safe to rule out acute pulmonary embolism?
AB  - : Essentials A stand-alone D-dimer below 750 MUg/L has been proposed to rule out
      acute pulmonary embolism (PE). This was a post-hoc analysis on data from 6
      studies comprising 7268 patients with suspected PE. The negative predictive value
      of a D-dimer <750 MUg/L ranged from 79% to 96% in various subgroups. Stand-alone
      D-dimer testing seems to be unsafe to rule out PE in all patients. SUMMARY:
      Background Recently, stand-alone D-dimer testing at a positivity threshold of 750
      MUg L-1 has been proposed as a safe and efficient approach to rule out acute
      pulmonary embolism (PE), without additional imaging, but this approach needs
      validation. Objectives To evaluate stand-alone D-dimer testing at a positivity
      threshold of 750 MUg L-1 to rule out PE. Methods Individual data from 7268
      patients with suspected PE previously enrolled in six prospective management
      studies were used. Patients were assessed by the Wells rule followed by
      quantitative D-dimer testing in those with a 'PE unlikely' score. Patients were
      classified post hoc as having a negative (< 750 MUg L-1 ) or positive (>= 750 MUg
      L-1 ) D-dimer. Using a one-stage meta-analytic approach, the negative predictive
      value (NPV) of stand-alone D-dimer testing was evaluated overall and in different
      risk subgroups. Results The pooled incidence of PE was 23% (range, 13-42%).
      Overall, 44% of patients had a D-dimer < 750 MUg L-1 , of whom 2.8% were
      diagnosed with PE at baseline or during 3-month follow-up (NPV, 97.2%; 95%
      confidence interval [CI], 94.9-98.5). The NPV was highest in patients with a low
      probability of PE according to the Wells rule (99.2%; 95% CI, 98.6-99.5%) and
      lowest in those with a high probability of PE (79.3%; 95% CI, 53.0-92.8%). The
      NPVs in patients with active cancer, patients with previous venous
      thromboembolism and inpatients were 96.2% (95% CI, 85.6-99.1%), 94.7% (95% CI,
      88.6-97.6%) and 92.7% (95% CI, 79.3-97.7%), respectively. Conclusions Our
      findings suggest that stand-alone D-dimer testing at a positivity threshold of
      750 MUg L-1 is not safe to rule out acute PE.

PMID- 27873440
TI  - Collective decision-making promotes fitness loss in a fusion-fission society.
AB  - While collective decision-making is recognised as a significant contributor to
      fitness in social species, the opposite outcome is also logically possible. We
      show that collective movement decisions guided by individual bison sharing faulty
      information about habitat quality promoted the use of ecological traps. The
      frequent, but short-lived, associations of bison with different spatial knowledge
      led to a population-wide shift from avoidance to selection of agricultural
      patches over 9 years in and around Prince Albert National Park, Canada. Bison
      were more likely to travel to an agricultural patch for the first time by
      following conspecifics already familiar with agricultural patches. Annual adult
      mortality increased by 12% due to hunting of bison on agricultural lands.
      Maladaptive social behaviour accordingly was a major force that contributed to a
      ~50% population decline in less than a decade. In human-altered landscapes,
      social learning by group-living species can lead to fitness losses, particularly
      in fusion-fission societies.

PMID- 27873441
TI  - Iridium versus Iridium: Nanocluster and Monometallic Catalysts Carrying the Same
      Ligand Behave Differently.
AB  - A specific secondary phosphine oxide (SPO) ligand (tert-butyl(phenyl)phosphine
      oxide) was employed to generate two iridium catalysts, an Ir-SPO complex and
      IrNPs (iridium nanoparticles) ligated with SPO ligands, which were compared
      mutually and with several supported iridium catalysts with the aim to establish
      the differences in their catalytic properties. The Ir-SPO-based catalysts showed
      totally different activities and selectivities in the hydrogenation of various
      substituted aldehydes, in which H2 is likely cleaved by a metal-ligand
      cooperation, that is, the SPO ligand and a neighboring metal centre operate in
      tandem to activate the hydrogen molecule. In addition, the supported IrNPs behave
      very differently from both Ir-SPO catalysts. This study exemplifies perfectly the
      advantages and disadvantages related to the use of the main types of catalysts,
      and thus the dissimilarities between them.

PMID- 27873436
TI  - Alternate glycemic markers reflect glycemic variability in continuous glucose
      monitoring in youth with prediabetes and type 2 diabetes.
AB  - OBJECTIVE: To determine whether the alternate glycemic markers, fructosamine
      (FA), glycated albumin (GA), and 1,5-anhydroglucitol (1,5AG), predict glycemic
      variability captured by continuous glucose monitoring (CGM) in obese youth with
      prediabetes and type 2 diabetes (T2D). STUDY DESIGN: Youth with BMI >=85th%ile,
      10-18 years, had collection of fasting plasma glucose (FPG), hemoglobin A1c
      (HbA1c), FA, GA, and 1,5AG and 72 hours of CGM. Participants with HbA1c >=5.7%
      were included. Relationships between glycemic markers and CGM variables were
      determined with Spearman correlation coefficients. Linear models were used to
      examine the association between alternate markers and CGM measures of glycemic
      variability-standard deviation (SD) and mean amplitude of glycemic excursions
      (MAGE)-after controlling for HbA1c. RESULTS: Total n = 56; Median (25th%ile,
      75th%ile) age = 14.3 years (12.5, 15.9), 32% male, 64% Hispanic, 20% black, 13%
      white, HbA1c = 5.9% (5.8, 6.3), FA=211 mmol/L (200, 226), GA= 12% (11%, 12%), and
      1,5AG = 22mcg/mL (19, 26). HbA1c correlated with average sensor glucose, AUC, SD,
      MAGE, and %time > 140 mg/dL. FA and GA correlated with average and peak sensor
      glucose, %time >140 and >200 mg/dL, and MAGE. GA also correlated with SD and
      AUC180. 1,5AG correlated with peak glucose, AUC180, SD, and MAGE. After adjusting
      for HbA1c, all 3 markers independently predicted MAGE; FA and GA independently
      predicted SD. CONCLUSIONS: Alternate glycemic markers predict glycemic
      variability as measured by CGM in youth with prediabetes and T2D. After adjusting
      for HbA1c, these alternate markers continued to predict components of glycemic
      variability detected by CGM.

PMID- 27873442
TI  - Forced deflation pulmonary function test: a novel method to evaluate lung
      function in infants and young children.
AB  - We describe the safety and feasibility of a forced deflation pulmonary function
      test (dPFT) in infants and young children. Fifty-two dPFT studies were performed
      in 26 patients (median age, 1.4 years). Forced vital capacity (FVC) and forced
      expiratory flow (FEF75 ) were normal in all except one case, but respiratory
      system compliance (Crs) was reduced in 24% patients. There were no significant
      differences in pre-blood and marrow transplantation FVC, FEF75 , and Crs between
      those patients who did and those who did not have posttransplant pulmonary
      complications. A larger study is needed to determine the prevalence and
      significance of PFT abnormalities in this age group.

PMID- 27873443
TI  - Assessing long-term effects of multiple, potentially confounded drivers in
      ecosystems from species traits.
AB  - Although species traits have the potential to disentangle long-term effects of
      multiple, potentially confounded drivers in ecosystems, this issue has received
      very little attention in the literature. We aimed at filling this gap by
      assessing the relative effects of hydroclimatic and water quality factors on the
      trait composition of invertebrate assemblages over 30 years in the Middle Loire
      River (France). Using a priori predictions on the long-term variation of trait
      based adaptations over the three decades, we evaluated the ability of
      invertebrate traits to indicate the effects of warming, discharge reduction and
      water quality improvement. Hydroclimatic and water quality factors contributed to
      up to 65% of the variation in trait composition. More than 70% of the initial
      trait response predictions made according to observed long-term hydroclimatic
      changes were confirmed. They supported a general climate-induced trend involving
      adapted resistance and resilience strategies. A partial confounding effect of
      water quality improvement acting on trophic processes was also highlighted,
      indicating that improved water quality management can significantly help to
      reduce some adverse effects of climate change. This trait-based approach can have
      wider implications for investigating long-term changes driven by multiple,
      potentially confounded factors, as frequently encountered in the context of
      global change.

PMID- 27873444
TI  - The effects of menstrual phase on orthodontic pain following initial archwire
      engagement.
AB  - OBJECTIVES: To explore the effects of menstrual cycle on orthodontic pain
      following initial archwire engagement. METHODS: Female participants with regular
      menstrual cycles were recruited and assigned into follicular group or luteal
      group. Demographical and baseline variables were collected: age, education,
      menstrual duration, anxiety, oral health impact profile-14 (OHIP-14), and index
      of complexity outcome and need (ICON). Following initial archwire engagement,
      orthodontic pain was determined through visual analogue scale (VAS) on 1st day,
      2nd day, and 3rd day. Demographical and baseline variables were compared between
      the two groups. Two-way repeated-measures anova was used to examine the effects
      of menstrual phase, time, and their interactions on orthodontic pain.
      Multivariate linear regression was employed to examine the independent effect of
      each variable on orthodontic pain. RESULTS: Finally, 37 and 39 were assigned to
      the follicular and luteal groups, respectively, with balanced demographical and
      baseline data. Orthodontic pain was significantly affected by menstrual phase and
      time (both P < 0.001), but there was no interaction (P > 0.05). Moreover,
      orthodontic pain was independently predicted by menstrual phase, OHIP, education
      level, and anxiety (all P < 0.05). CONCLUSION: We suggest that practitioners
      arrange female patients to receive initial archwire engagement during their
      follicular phases to relieve orthodontic pain.

PMID- 27873445
TI  - The motion of a living conspecific activates septal and preoptic areas in naive
      domestic chicks (Gallus gallus).
AB  - Predispositions to attend to animate objects are ubiquitous in newborn
      vertebrates, but little is known about their neural bases. In this study, we
      wanted to know if exposure to the motion of a living, behaving conspecific will
      selectively activate septal, preoptic and amygdaloid areas in visually naive
      domestic chicks. For this purpose, newly hatched chicks were exposed to a live
      conspecific, whose natural motion presents of course several features typical of
      animate motion to which chicks are known to be sensitive. In the control group,
      chicks were exposed to a rotating stuffed chick that showed rigid non-biological
      motion. The two stimuli were visually matched with regard to their static
      features. We measured brain activity by visualizing the immediate early gene
      product c-Fos with a standard immunohistochemical procedure. Notably, dorsal
      right septum and left preoptic area showed higher activation in experimental
      subjects compared to the control animals. This is, to the best of our knowledge,
      the first demonstration of septal and preoptic areas involvement in response to
      the animate motion of a social partner, as opposed to rigid motion of a similarly
      looking stimulus. Moreover, these results indicate that previous visual
      experience and specific learning events are not necessary to establish the septal
      and preoptic areas function, which is present shortly after birth.

PMID- 27873446
TI  - The First 2 Years of Activity of a Specialized Organ Procurement Center: Report
      of an Innovative Approach to Improve Organ Donation.
AB  - The number of patients requiring organ transplants continues to outgrow the
      number of organs donated each year. In an attempt to improve the organ donation
      process and increase the number of organs available, we created a specialized
      multidisciplinary team within a specialized organ procurement center (OPC) with
      dedicated intensive care unit (ICU) beds and operating rooms. The OPC was staffed
      with ICU nurses, operating room nurses, organ donor management ICU physicians,
      and multidisciplinary staff. All organ donors within a designated geographic area
      were transferred to and managed within the OPC. During the first 2 years of
      operation, 126 patients were referred to the OPC. The OPC was in use for a total
      of 3527 h and involved 253 health workers. We retrieved 173 kidneys, 95 lungs, 68
      livers, 37 hearts, and 13 pancreases for a total of 386 organs offered for
      transplantation. This translates to a total of 124.6 persons transplanted per
      million population, which compares most favorably to recently published numbers
      in developed countries. The OPC clearly demonstrates potential to increase the
      number of deceased donor organs available for transplant. Further studies are
      warranted to better understand the exact influence of the different components of
      the OPC on organ procurement.

PMID- 27873447
TI  - Electroless Deposition of Nickel on Photografted Polymeric Microscale Patterns.
AB  - This report demonstrates the electroless deposition of Ni onto micropatterns of
      poly (acrylic acid) (PAA) photografted to phthalimide-terminated self-assembled
      monolayers (SAMs). PAA is spin-coated onto phthalimide SAMs and covered with a
      photomask. UV irradiation selectively binds PAA to exposed regions of the
      surface, allowing PAA on unexposed regions to be rinsed off. A Pd catalyst is
      then selectively adsorbed to regions of the surface where PAA is bound. The
      adsorbed catalyst selectively initiates Ni plating upon immersion of the
      substrate into a Ni(SO4 ) bath.

PMID- 27873448
TI  - Multibuilding Block Janus Synthesized by Seed-Mediated Self-Assembly for Enhanced
      Photothermal Effects and Colored Brownian Motion in an Optical Trap.
AB  - The asymmetrical features and unique properties of multibuilding block Janus
      nanostructures (JNSs) provide superior functions for biomedical applications.
      However, their production process is very challenging. This problem has hampered
      the progress of JNS research and the exploration of their applications. In this
      study, an asymmetrical multibuilding block gold/iron oxide JNS has been generated
      to enhance photothermal effects and display colored Brownian motion in an optical
      trap. JNS is formed by seed-mediated self-assembly of nanoparticle-loaded
      thermocleavable micelles, where the hydrophobic backbones of the polymer are
      disrupted at high temperatures, resulting in secondary self-assembly and
      structural rearrangement. The JNS significantly enhances photothermal effects
      compared to their homogeneous counterpart after near-infrared (NIR) light
      irradiation. The asymmetrical distribution of gold and iron oxide within JNS also
      generates uneven thermophoretic force to display active colored Brownian
      rotational motion in a single-beam gradient optical trap. These properties
      indicate that the asymmetrical JNS could be employed as a strong photothermal
      therapy mediator and a fuel-free nanoscale Janus motor under NIR light.

PMID- 27873449
TI  - Assessment of cubosomal alpha lipoic acid gel efficacy for the aging face: a
      single-blinded, placebo-controlled, right-left comparative clinical study.
AB  - BACKGROUND: A poloxamer solution acting as a vehicle for the lipid base
      particulate system (cubosome dispersions) containing alpha lipoic acid (ALA) has
      achieved encouraging results in skin aging. OBJECTIVE: Evaluate the efficacy of
      5% Cubosomal ALA as an anti-aging formulation. METHODS: This single-blinded,
      placebo-controlled, comparative study was conducted on 20 females. Patients were
      instructed to apply a gel formulation containing the active ingredient over the
      right half of their face and a placebo gel on the left half twice daily for 6
      months. Global aesthetic improvement scale (GAIS) was utilized as a measure of
      clinical progress. The thicknesses of the epidermis and dermis were assessed
      before and after treatment using an ultrasound biomicroscope. RESULTS: The GAIS
      score assessment at 3 and 6 months showed a significantly greater improvement on
      the right sides in comparison with the left sides. At the end of the treatment
      period, the mean epidermal thickness significantly increased on the right side in
      comparison with the left side and the mean dermal thickness increased more on the
      right side in comparison with the left side; however, this difference was not
      significant. CONCLUSION: 5% Cubosomal ALA is an effective and safe modality for
      improving aging face.

PMID- 27873450
TI  - The arc of fellowship.

PMID- 27873451
TI  - A prospective randomized trial comparing piperacillin/tazobactam with meropenem
      as empirical antibiotic treatment of febrile neutropenic children and adolescents
      with hematologic and malignant disorders.
AB  - BACKGROUND: This randomized prospective study was designed to assess whether
      piperacillin/tazobactam (PIPC/TAZ) is as effective as meropenem (MEPM) as a first
      line antibiotic treatment for febrile neutropenia (FN). PROCEDURE: FN episodes
      were randomly assigned to receive either PIPC/TAZ (337.5 mg/kg per day in three
      doses, 1-hr DIV, maximum 13.5 g per day) or MEPM (120 mg/kg per day in three
      doses, 1-hr DIV, maximum 3 g per day). Clinical responses were evaluated 120 hr
      after the DIV. RESULTS: A total of 434 febrile episodes in 105 patients (42
      females and 63 males) with a median age of 8 years (range 0-25) were included in
      this trial. Blood cultures were positive in 47 out of the 434 episodes (10.8%).
      Regarding responses to the treatment, success rates between the PIPC/TAZ and MEPM
      groups were similar (62.4 vs. 65.9%, P = 0.484), even if patients were restricted
      to those with bacteremia (26.1 vs 37.5%, P = 0.534). Mortality rates did not
      significantly differ between the two groups (0.8 vs. 0%, P = 0.500). CONCLUSION:
      Both PIPC/TAZ and MEPM appeared to be equally efficacious and safe. Carbapenems
      are now broadly used to treat FN; however, this may increase the prevalence of
      drug-resistant bacteria. In this regard, the treatment using PIPC/TAZ for FN is
      more beneficial.

PMID- 27873452
TI  - Improving clinical prognostic stratification models for men with prostate cancer:
      a practical step closer to more individualized care without added costs.

PMID- 27873454
TI  - Comment on tobacco use among siblings of childhood cancer survivors: A report
      from the childhood cancer survivor study.

PMID- 27873453
TI  - Does improvement of cognitive functioning by cognitive remediation therapy effect
      work outcomes in severe mental illness? A secondary analysis of a randomized
      controlled trial.
AB  - AIM: The aim of this study was to clarify whether improvement of cognitive
      functioning by cognitive remediation therapy can improve work outcome in
      schizophrenia and other severe mental illnesses when combined with supported
      employment. METHODS: The subjects of this study were persons with severe mental
      illness diagnosed with schizophrenia, major depression, or bipolar disorder (ICD
      10) and cognitive dysfunction who participated in both cognitive remediation
      using the Thinking Skills for Work program and a supported employment program in
      a multisite, randomized controlled study. Logistic and multiple linear regression
      analyses were performed to clarify the influence of cognitive functioning on
      vocational outcomes, adjusting for demographic and clinical variables. RESULTS:
      Improvement of cognitive functioning with cognitive remediation significantly
      contributed to the total days employed and total earnings of competitive
      employment in supported employment service during the study period. Any baseline
      demographic and clinical variables did not significantly contribute to the work
      related outcomes. CONCLUSION: A cognitive remediation program transferring
      learning skills into the real world is useful to increase the quality of working
      life in supported employment services for persons with severe mental illness and
      cognitive dysfunction who want to work competitively.

PMID- 27873455
TI  - Catalytic Asymmetric Reductive Condensation of N-H Imines: Synthesis of C2 
      Symmetric Secondary Amines.
AB  - A highly diastereoselective and enantioselective Bronsted acid catalyzed
      reductive condensation of N-H imines was developed. This reaction is catalyzed by
      a chiral disulfonimide (DSI), uses Hantzsch esters as a hydrogen source, and
      delivers useful C2 -symmetric secondary amines.

PMID- 27873456
TI  - Visceral leishmaniasis in two patients with IL-12p40 and IL-12Rbeta1
      deficiencies.
AB  - Mutations of the IL12B and IL12RB1 genes underlie the development of IL-12 p40
      and IL-12Rbeta1 deficiencies, respectively, both of which cause predisposition to
      infection with weakly virulent mycobacteria and Salmonella. Infections with other
      intramacrophagic organisms have only been rarely observed. We identified two
      patients with visceral leishmaniasis who had autosomal recessive IL-12 p40 and IL
      12Rbeta1 deficiencies, respectively. This finding demonstrates the importance of
      IFN-gamma immunity in the control of leishmaniasis. We also searched the
      literature for similar reports in patients with these and other primary
      immunodeficiencies.

PMID- 27873457
TI  - Using yeast to determine the functional consequences of mutations in the human
      p53 tumor suppressor gene: An introductory course-based undergraduate research
      experience in molecular and cell biology.
AB  - The opportunity to engage in scientific research is an important, but often
      neglected, component of undergraduate training in biology. We describe the
      curriculum for an innovative, course-based undergraduate research experience
      (CURE) appropriate for a large, introductory cell and molecular biology
      laboratory class that leverages students' high level of interest in cancer. The
      course is highly collaborative and emphasizes the analysis and interpretation of
      original scientific data. During the course, students work in teams to
      characterize a collection of mutations in the human p53 tumor suppressor gene via
      expression and analysis in yeast. Initially, student pairs use both qualitative
      and quantitative assays to assess the ability of their p53 mutant to activate
      expression of reporter genes, and they localize their mutation within the p53
      structure. Through facilitated discussion, students suggest possible molecular
      explanations for the transactivation defects displayed by their p53 mutants and
      propose experiments to test these hypotheses that they execute during the second
      part of the course. They use a western blot to determine whether mutant p53
      levels are reduced, a DNA-binding assay to test whether recognition of any of
      three p53 target sequences is compromised, and fluorescence microscopy to assay
      nuclear localization. Students studying the same p53 mutant periodically convene
      to discuss and interpret their combined data. The course culminates in a poster
      session during which students present their findings to peers, instructors, and
      the greater biosciences community. Based on our experience, we provide
      recommendations for the development of similar large introductory lab courses.
      (c) 2016 by The International Union of Biochemistry and Molecular Biology,
      45(2):161-178, 2017.

PMID- 27873459
TI  - Bedside rounds.

PMID- 27873458
TI  - Resveratrol enhances brown adipocyte formation and function by activating AMP
      activated protein kinase (AMPK) alpha1 in mice fed high-fat diet.
AB  - SCOPE: Enhancing the formation and function of brown adipose tissue (BAT)
      increases thermogenesis and hence reduces obesity. Thus, we investigate the
      effects of resveratrol (Resv) on brown adipocyte formation and function in mouse
      interscapular BAT (iBAT). METHODS AND RESULTS: CD1 mice and stromal vascular
      cells (SVCs) isolated from iBAT were treated with Resv. Expression of brown
      adipogenic and thermogenic markers, and involvement of AMP-activated protein
      kinase (AMPK)alpha1 were assessed. In vivo, Resv-enhanced expression of brown
      adipogenic markers, PR domain-containing 16 (PRDM16) and thermogenic genes,
      uncoupling protein 1 (UCP1) and cytochrome C in iBAT, along with smaller lipid
      droplets, elevated AMPKalpha activity and increased oxygen consumption.
      Meanwhile, Resv promoted expression of PRDM16, UCP1, PGC1alpha, cytochrome C and
      pyruvate dehydrogenase (PDH) in differentiated iBAT SVCs, suggesting that Resv
      enhanced brown adipocyte formation and function in vitro. In addition, Resv
      stimulated AMPKalpha and oxygen consumption in differentiated iBAT SVCs. However,
      the promotional effects of Resv were diminished by AMPK inhibition or AMPKalpha1
      knockout, implying the involvement of AMPKalpha1 in this process. CONCLUSION:
      Resv enhanced brown adipocyte formation and thermogenic function in mouse iBAT by
      promoting the expression of brown adipogenic markers via activating AMPKalpha1,
      which contributed to the anti-obesity effects of Resv.

PMID- 27873460
TI  - Sortase A-Generated Highly Potent Anti-CD20-MMAE Conjugates for Efficient
      Elimination of B-Lineage Lymphomas.
AB  - Antibody-drug conjugate (ADC) targeting antigens expressed on the surface of
      tumor cells are an effective approach for delivering drugs into the cells via
      antigen-mediated endocytosis. One of the well-known tumor antigens, the CD20 of B
      lymphocyte, has long been suggested to be noninternalizing epitope, and is thus
      not considered a desirable target for ADCs. Here, sortase A (srtA)-mediated
      transpeptidation is used to specifically conjugate triple glycine-modified
      monomethyl auristatin E (MMAE), a highly toxic antimitotic agent, to anti-CD20
      ofatumumab (OFA) equipped with a short C-terminal LPETG (5 amino acids) tag at
      heavy chain (HL), which generates ADCs that show extremely strong potency in
      killing CD20 positive cancer cells. One of the srtA-generated ADCs with a
      cleavable dipeptide linker (valine-citrulline, vc), OFA-HL-vcMMAE, shows IC50
      values ranging from 5 pg mL-1 to 4.1 ng mL-1 against CD20+ lymphoma cells.
      Confocal laser scanning microscopy confirms that OFA-HL-vcMMAE internalization by
      Ramos cells is significantly improved compared to OFA alone, consistent with the
      high antitumor activity of the new ADC. OFA-HL-vcMMAE, at 5 mg kg-1 dose, is able
      to eliminate tumors with mean volume ~400 mm3 while no obvious drug-related
      toxicity is observed. The results show that srtA-generated OFA-MMAE conjugate
      system provides a viable strategy for targeting CD20+ B lineage lymphomas.

PMID- 27873461
TI  - Human peripheral blood mononuclear cell in vitro system to test the efficacy of
      food bioactive compounds: Effects of polyunsaturated fatty acids and their
      relation with BMI.
AB  - SCOPE: To analyse the usefulness of isolated human peripheral blood mononuclear
      cells (PBMC) to rapidly/easily reflect n-3 long-chain polyunsaturated fatty acid
      (LCPUFA) effects on lipid metabolism/inflammation gene profile, and evaluate if
      these effects are body mass index (BMI) dependent. METHODS AND RESULTS: PBMC from
      normoweight (NW) and overweight/obese (OW/OB) subjects were incubated with
      physiological doses of docosahexaenoic (DHA), eicosapentaenoic acid (EPA), or
      their combination. PBMC reflected increased beta-oxidation-like capacity (CPT1A
      expression) in OW/OB but only after DHA treatment. However, insensitivity to n-3
      LCPUFA was evident in OW/OB for lipogenic genes: both PUFA diminished FASN and
      SREBP1C expression in NW, but no effect was observed for DHA in PBMC from high
      BMI subjects. This insensitivity was also evident for inflammation gene profile:
      all treatments inhibited key inflammatory genes in NW; nevertheless, no effect
      was observed in OW/OB after DHA treatment, and EPA effect was impaired. SLC27A2,
      IL6 and TNFalpha PBMC expression analysis resulted especially interesting to
      determine obesity-related n-3 LCPUFA insensitivity. CONCLUSION: A PBMC-based
      human in vitro system reflects n-3 LCPUFA effects on lipid
      metabolism/inflammation which is impaired in OW/OB. These results confirm the
      utility of PBMC ex vivo systems for bioactive-compound screening to promote
      functional food development and to establish appropriate dietary strategies for
      obese population.

PMID- 27873463
TI  - Preparation of carbon quantum dots based high photostability luminescent
      membranes.
AB  - Urethane acrylate (UA) was used to prepare carbon quantum dots (C-dots)
      luminescent membranes and the resultants were examined with FT-IR, mechanical
      strength, scanning electron microscope (SEM) and quantum yields (QYs). FT-IR
      results showed the polyurethane acrylate (PUA) prepolymer -C = C-vibration at
      1101 cm-1 disappeared but there was strong vibration at1687cm-1 which was
      contributed from the-C = O groups in cross-linking PUA. Mechanical strength
      results showed that the different quantity of C-dots loadings and UV-curing time
      affect the strength. SEM observations on the cross-sections of the membranes are
      uniform and have no structural defects, which prove that the C-dots are
      compatible with the water-soluble PUA resin. The C-dot loading was increased from
      0 to 1 g, the maximum tensile stress was nearly 2.67 MPa, but the tensile strain
      was decreased from 23.4% to 15.1% and 7.2% respectively. QYs results showed that
      the C-dots in the membrane were stable after 120 h continuous irradiation.
      Therefore, the C-dots photoluminescent film is the promising material for the
      flexible devices in the future applications.

PMID- 27873462
TI  - Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases:
      Pathogenesis and Treatment.
AB  - Neurodegenerative diseases are a heterogeneous group of disorders that are
      incurable and characterized by the progressive degeneration of the function and
      structure of the central nervous system (CNS) for reasons that are not yet
      understood. Neurodegeneration is the umbrella term for the progressive death of
      nerve cells and loss of brain tissue. Because of their high energy requirements,
      neurons are especially vulnerable to injury and death from dysfunctional
      mitochondria. Widespread damage to mitochondria causes cells to die because they
      can no longer produce enough energy. Several lines of pathological and
      physiological evidence reveal that impaired mitochondrial function and dynamics
      play crucial roles in aging and pathogenesis of neurodegenerative diseases. As
      mitochondria are the major intracellular organelles that regulate both cell
      survival and death, they are highly considered as a potential target for
      pharmacological-based therapies. The purpose of this review was to present the
      current status of our knowledge and understanding of the involvement of
      mitochondrial dysfunction in pathogenesis of neurodegenerative diseases including
      Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD),
      and amyotrophic lateral sclerosis (ALS) and the importance of mitochondrial
      biogenesis as a potential novel therapeutic target for their treatment. Likewise,
      we highlight a concise overview of the key roles of mitochondrial electron
      transport chain (ETC.) complexes as well as mitochondrial biogenesis regulators
      regarding those diseases.

PMID- 27873464
TI  - Hyalinosis Lesions in Renal Transplant Biopsies: Time-Dependent Complexity of
      Interpretation.
AB  - Because calcineurin inhibitor (CNI) immunosuppressive drugs induce arteriolar
      hyalinosis (ah) in kidney transplants, ah lesions can potentially provide
      information about drug exposure. We studied the relationship of ah lesions to
      findings and outcomes in 562 indication biopsies taken 3 days to 35 years after
      transplant. Prevalence of ah lesions increased with time of biopsy after
      transplant (TxBx). The ah scores correlated with arterial intimal thickening and
      atrophy-fibrosis but, unlike atrophy-fibrosis, did not increase until after 500
      days because of a background of ah1 lesions in early biopsies reflecting donor
      aging. Correlation of ah scores with other features varied with TxBx-in early
      biopsies, donor age and related changes, and in very late biopsies, chronic
      antibody-mediated rejection and glomerulonephritis and associated lesions. After
      correction for TxBx, ah0 in intermediate time periods was associated with
      increased risk of T cell-mediated rejection and graft loss, probably because of
      underimmunosuppression and nonadherence. Thus, ah lesions in indication biopsies
      have multiple associations: donor age (early, usually ah1), chronic glomerular
      diseases (late, often ah2/3), and adequate exposure to CNIs at intermediate
      times. This threefold TxBx-dependent complexity must be considered when
      interpreting indication biopsies: ah lesions often indicate adequate CNI
      exposure, not toxicity, and unexpected ah0 should increase vigilance for
      nonadherence and underimmunosuppression.

PMID- 27873465
TI  - A warm welcome for alternative CO2 fixation pathways in microbial biotechnology.

PMID- 27873466
TI  - Cortical folding in post-traumatic stress disorder after motor vehicle accidents:
      Regional differences in gyrification.
AB  - AIM: Structural and functional magnetic resonance imaging (MRI) studies have
      revealed evidence of brain abnormalities in post-traumatic stress disorder (PTSD)
      patients. Cortical complexity and local gyrification index (lGI) reflect
      potential biological processes associated with normal or abnormal cognitive
      functioning. In the current study, lGI was used to explore cortical folding in
      PTSD patients involved in motor vehicle accidents (MVA). METHODS: MRI brain scans
      were acquired from 18 PTSD patients who had suffered MVA at least 6 months
      previously and 18 healthy control subjects. All MRI images were obtained on a 3-T
      Siemens MRI machine and the cortical folding was analyzed using the workflow
      provided by software FreeSurfer. A general FreeSurfer's general linear model was
      used in the group analysis. In addition, correlation analysis was performed
      between the average of lGI extracted from the significantly different areas and
      the data for the clinical scale. RESULTS: The PTSD patients had significantly
      greater Clinician-Administered PTSD Scale scores than the control group. The
      patients showed significantly reduced lGI in the left lateral orbitofrontal
      cortex, consistent with findings of previous volumetric studies on PTSD. But
      there were no significant correlations in the left lateral orbitofrontal cortex
      between Clinician-Administered PTSD Scale scores and lGI. CONCLUSION: We suggest
      that abnormal gyrification in PTSD patients can be an important indicator of
      neurodevelopment deficits and may indeed be a biological marker for PTSD.

PMID- 27873467
TI  - Enhancing Electrocatalytic Performance of Bifunctional Cobalt-Manganese
      Oxynitride Nanocatalysts on Graphene.
AB  - We report the synthesis and characterization of graphenesupported cobalt
      manganese-oxynitride nanocatalysts (CoMnON/G) as bifunctional electrocatalysts
      for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). A
      nitriding treatment of spinel compound CoMnO increased the ORR activity
      considerably, and the most active material catalyzed the ORR with only a 30 mV
      half-wave potential difference from the commercial carbon-supported platinum
      (Pt/C) in alkaline media. In addition to high activity, the catalyst also
      exhibited an intrinsic stability that outperformed Pt/C. An appropriately
      designed nitridation thus facilitates new directions for developing active and
      durable non-precious-metal oxynitride electocatalysts.

PMID- 27873468
TI  - Synthetic Mucin-Like Glycopeptides as Versatile Tools to Measure Effects of
      Glycan Structure/Density/Position on the Interaction with Adhesion/Growth
      Regulatory Galectins in Arrays.
AB  - Functional pairing of cellular glycoconjugates with tissue lectins is a highly
      selective process, whose determinative factors have not yet been fully
      delineated. Glycan structure and modes of presentation, that is, its position and
      density, can contribute to binding, as different members of a lectin family can
      regulate degrees of responsiveness to these factors. Using a peptide repeat
      sequence motif of the glycoprotein mucin-1, the principle of introducing
      synthetic (glyco)peptides with distinct variations in these three parameters to
      an array-based screening of tissue lectins is illustrated. Interaction profiles
      of seven adhesion/growth-regulatory galectins cover the range from intense
      signals with core 2 pentasaccharides and core 1 binding for galectins-3 and -5 to
      a lack of binding for galectin-1 and also the galectin-related protein, which was
      included as a negative control. Remarkably, the two tandem-repeat-type galectins
      4 and -8 were distinguished by core 1 sialylation, as the two separated domains
      were. These results encourage further synthetic elaboration of the glycopeptide
      library and testing of the network of natural galectins and rationally engineered
      variants of the lectins.

PMID- 27873469
TI  - Variation of cytopathologists' use of the indeterminate diagnostic categories
      "atypical" and "suspicious for malignancy" in the cytologic diagnosis of solid
      pancreatic lesions on endoscopic ultrasound-guided fine-needle aspirates.
AB  - : Indeterminate cytologic diagnoses in endoscopic ultrasound guided fine needle
      aspiration biopsy (EUS-FNA) of solid pancreatic lesions include the diagnostic
      categories "atypical" (ATY) and "suspicious for malignancy" (SUSP), which are
      used at variable rates and are associated with variable underlying risk of
      malignancy. The aim of this study was to determine individual cytopathologists'
      rates of indeterminate diagnoses in EUS-FNA of solid pancreatic lesions and their
      relationship to cytopathologists' experience and volume of pancreatic EUS-FNA
      examined, as well as the potential impact of departmental consensus review on
      indeterminate diagnoses. DESIGN: The diagnostic rates of ATY and SUSP and their
      underlying risk of malignancy were calculated for six cytopathologists who
      diagnosed 1,114 of 1,225 EUS-FNA of solid pancreatic lesions from 1/1/2001 to
      9/15/2014, and were then compared for the periods before and after the
      implementation of departmental consensus review during 2009. RESULTS: The six
      cytopathologists diagnosed 10% of cases as indeterminate; 82 (7.4%) as "atypical"
      and 29 (2.6%) as "suspicious". The individual cytopathologists' indeterminate
      diagnosis rates varied twofold (6.67-12.80%) and did not correlate with their
      experience, total or annual volume of EUS-FNAs. Of the 56/99 (56.57%) cases with
      follow-up, the underlying rate of malignancy was 47% (35/75; for "atypical" and
      87.5% (21/24); for "suspicious"). The underlying rates of malignancy were 33-67%
      for "atypical" and 80-100% for "suspicious" diagnoses made by individual
      cytopathologists. The rate of indeterminate diagnoses decreased from 11.55 to
      7.88% after the implementation of departmental consensus review. CONCLUSION:
      Individual cytopathologists' rates of indeterminate diagnoses and their
      significance vary; however, consensus review is helpful in reducing these rates.
      Diagn. Cytopathol. 2017;45:3-13. (c) 2016 Wiley Periodicals, Inc.

PMID- 27873470
TI  - Migration highways and migration barriers created by host-parasite interactions.
AB  - Co-evolving parasites may play a key role in host migration and population
      structure. Using co-evolving bacteria and viruses, we test general hypotheses as
      to how co-evolving parasites affect the success of passive host migration between
      habitats that can support different intensities of host-parasite interactions.
      First, we show that parasites aid migration from areas of intense to weak co
      evolutionary interactions and impede migration in the opposite direction, as a
      result of intraspecific apparent competition mediated via parasites. Second, when
      habitats show qualitative difference such that some environments support parasite
      persistence while others do not, different population regulation forces (either
      parasitism or competitive exclusion) will reduce the success of migration in both
      directions. Our study shows that co-evolution with parasites can predictably
      homogenises or isolates host populations, depending on heterogeneity of abiotic
      conditions, with the second scenario constituting a novel type of 'isolation by
      adaptation'.

PMID- 27873471
TI  - Mitsuda psychosis and holodysphrenia revisited: An atypical psychosis in a
      patient with parieto-occipital paroxysmal electroencephalographic activity and
      high unconjugated bilirubin.

PMID- 27873474
TI  - Spectrum of gallbladder malignancies on fine-needle aspiration cytology: 5 years
      retrospective single institutional study with emphasis on uncommon variants.
AB  - BACKGROUND: Ultrasound-guided fine-needle aspiration cytology (FNAC) is the
      standard modality for diagnosis of gallbladder malignant neoplasms.
      Adenocarcinoma is the most common malignancy; however, other types may also be
      encountered. The aim of this study was to perform a retrospective analysis of
      gallbladder malignancies diagnosed on FNAC in the last 5 years to document the
      cytomorphological spectrum and the variations thereof. METHODS: The records of
      the Department of Cytology, PGIMER were searched from July 2010 to June 2015 and
      all cases of gallbladder malignancies were analyzed in detail for
      cytomorphological characteristics. Giemsa and Hematoxylin-Eosin stained slides
      were evaluated with immunocytochemistry on cell blocks wherever available.
      RESULTS: A total of 791 gallbladder FNAC performed in cases of radiologically
      suspected gallbladder malignancies were evaluated. Gallbladder carcinoma (GBC)
      was more common in females with a male to female ratio of 1:2.3. Median age was
      53.4 years (range 24-85 years); 81 cases (10.2%) were nondiagnostic and 31 (3.9%)
      were suspicious of malignancy. A total of 645 FNACs were positive for malignancy,
      out of which there were 619 (96%) adenocarcinoma and 26 cases with unusual
      malignancies. These included adenosquamous carcinoma (8, 1.2%), squamous cell
      carcinoma (7, 1.1%), small cell neuroendocrine carcinoma (9, 1.3%), and one case
      each of undifferentiated carcinoma and Non Hodgkin lymphoma respectively. The
      unusual malignancies were confirmed on cell block immunocytochemistry.
      CONCLUSION: Adenocarcinoma is most common type of gallbladder malignancy;
      however, other unusual types of carcinomas occur and in such cases, FNAC
      supplemented by cell block immunocytochemistry is required for an accurate
      diagnosis. Diagn. Cytopathol. 2017;45:36-42. (c) 2016 Wiley Periodicals, Inc.

PMID- 27873472
TI  - Perfect timing: splicing and transcription rates in living cells.
AB  - An important step toward understanding gene regulation is the elucidation of the
      time necessary for the completion of individual steps. Measurement of reaction
      rates can reveal potential nodes for regulation. For example, measurements of in
      vivo transcription elongation rates reveal regulation by DNA sequence, gene
      architecture, and chromatin. Pre-mRNA splicing is regulated by transcription
      elongation rates and vice versa, yet the rates of RNA processing reactions remain
      largely elusive. Since the 1980s, numerous model systems and approaches have been
      used to determine the precise timing of splicing in vivo. Because splicing can be
      co-transcriptional, the position of Pol II when splicing is detected has been
      used as a proxy for time by some investigators. In addition to these 'distance
      based' measurements, 'time-based' measurements have been possible through live
      cell imaging, metabolic labeling of RNA, and gene induction. Yet splicing rates
      can be convolved by the time it takes for transcription, spliceosome assembly and
      spliceosome disassembly. The variety of assays and systems used has, perhaps not
      surprisingly, led to reports of widely differing splicing rates in vivo.
      Recently, single molecule RNA-seq has indicated that splicing occurs more quickly
      than previously deduced. Here we comprehensively review these findings and
      discuss evidence that splicing and transcription rates are closely coordinated,
      facilitating the efficiency of gene expression. On the other hand, introduction
      of splicing delays through as yet unknown mechanisms provide opportunity for
      regulation. More work is needed to understand how cells optimize the rates of
      gene expression for a range of biological conditions. WIREs RNA 2017, 8:e1401.
      doi: 10.1002/wrna.1401 For further resources related to this article, please
      visit the WIREs website.

PMID- 27873473
TI  - Explanation and Elaboration Document for the STROBE-Vet Statement: Strengthening
      the Reporting of Observational Studies in Epidemiology - Veterinary Extension.
AB  - The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology)
      statement was first published in 2007 and again in 2014. The purpose of the
      original STROBE was to provide guidance for authors, reviewers and editors to
      improve the comprehensiveness of reporting; however, STROBE has a unique focus on
      observational studies. Although much of the guidance provided by the original
      STROBE document is directly applicable, it was deemed useful to map those
      statements to veterinary concepts, provide veterinary examples and highlight
      unique aspects of reporting in veterinary observational studies. Here, we present
      the examples and explanations for the checklist items included in the STROBE-Vet
      Statement. Thus, this is a companion document to the STROBE-Vet Statement Methods
      and process document, which describes the checklist and how it was developed.

PMID- 27873475
TI  - Electrochemical Coupling of Biomass-Derived Acids: New C8 Platforms for Renewable
      Polymers and Fuels.
AB  - Electrolysis of biomass-derived carbonyl compounds is an alternative to
      condensation chemistry for supplying products with chain length >C6 for biofuels
      and renewable materials production. Kolbe coupling of biomass-derived levulinic
      acid is used to obtain 2,7-octanedione, a new platform molecule only two low
      process-intensity steps removed from raw biomass. Hydrogenation to 2,7-octanediol
      provides a chiral secondary diol largely unknown to polymer chemistry, whereas
      intramolecular aldol condensation followed by hydrogenation yields branched
      cycloalkanes suitable for use as high-octane, cellulosic gasoline. Analogous
      electrolysis of an itaconic acid-derived methylsuccinic monoester yields a chiral
      2,5-dimethyladipic acid diester, another underutilized monomer owing to lack of
      availability.

PMID- 27873476
TI  - Older patients' consultations in an apprenticeship model-based general practice
      training program: A cross-sectional study.
AB  - OBJECTIVE: To investigate older patients' encounters with general practice
      registrars (GPRs) to inform training and clinical practice. METHODS: Cross
      sectional analysis of data from GPR consultations across five regional training
      providers in Australia. Data were analysed using simple and multiple logistic
      regression models. RESULTS: Our analysis included details of 118 831
      consultations, 20 555 (17.6%, 95% CI 17.4-17.8) with patients aged >=65 years.
      Older patient encounters had an increased likelihood of including chronic disease
      (OR 1.77, 95% CI 1.70, 1.86) and more problems (OR 1.24, 95% CI 1.20, 1.27).
      However, in-consultation information or advice was less likely to be sought (OR
      0.92, 95% CI 0.88, 0.97), and consultations were briefer (OR 0.99, 95% CI 0.99,
      1.00). CONCLUSION: Our results suggest relatively limited GPR exposure to older
      patients coupled with less complex consultations than expected. Solutions will
      need to be carefully constructed not only to increase caseloads, but also to
      address training and supervision concerns.

PMID- 27873478
TI  - Methods and Processes of Developing the Strengthening the Reporting of
      Observational Studies in Epidemiology - Veterinary (STROBE-Vet) Statement.
AB  - The reporting of observational studies in veterinary research presents many
      challenges that often are not adequately addressed in published reporting
      guidelines. A consensus meeting of experts was organized to develop an extension
      of the STROBE statement to address observational studies in veterinary medicine
      with respect to animal health, animal production, animal welfare and food safety
      outcomes. The consensus meeting was held 11-13 May 2014 in Mississauga, Ontario,
      Canada. Seventeen experts from North America, Europe and Australia attended the
      meeting. The experts were epidemiologists and biostatisticians, many of whom hold
      or have held editorial positions with relevant journals. Prior to the meeting, 19
      experts completed a survey about whether they felt any of the 22 items of the
      STROBE statement should be modified and whether items should be added to address
      unique issues related to observational studies in animal species with health,
      production, welfare or food safety outcomes. At the meeting, the participants
      were provided with the survey responses and relevant literature concerning the
      reporting of veterinary observational studies. During the meeting, each STROBE
      item was discussed to determine whether or not re-wording was recommended, and
      whether additions were warranted. Anonymous voting was used to determine whether
      there was consensus for each item change or addition. The consensus was that six
      items needed no modifications or additions. Modifications or additions were made
      to the STROBE items numbered as follows: 1 (title and abstract), 3 (objectives),
      5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9
      (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14
      (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19
      (limitations) and 22 (funding). Published literature was not always available to
      support modification to, or inclusion of, an item. The methods and processes used
      in the development of this statement were similar to those used for other
      extensions of the STROBE statement. The use of this extension to the STROBE
      statement should improve the reporting of observational studies in veterinary
      research related to animal health, production, welfare or food safety outcomes by
      recognizing the unique features of observational studies involving food-producing
      and companion animals, products of animal origin, aquaculture and wildlife.

PMID- 27873477
TI  - Telemedically Supported Case Management of Living-Donor Renal Transplant
      Recipients to Optimize Routine Evidence-Based Aftercare: A Single-Center
      Randomized Controlled Trial.
AB  - Improving mid-term and long-term outcomes after solid organ transplantation is
      imperative, and requires both state-of-the-art transplant surgery and
      optimization of routine, evidence-based aftercare. This randomized, controlled
      trial assessed the effectiveness of standard aftercare versus telemedically
      supported case management, an innovative aftercare model, in 46 living-donor
      renal transplant recipients during the first posttransplant year. The model
      includes three components: (i) chronic care case management initiated after
      discharge, (ii) case management initiated in emerging acute care situations, and
      (iii) a telemedically equipped team comprising a transplant nurse case manager
      and two senior transplant physicians (nephrologist, surgeon). Analyses revealed a
      reduction of unplanned inpatient acute care, with considerable cost reductions,
      in the intervention group. The prevalence of nonadherence over the 1-year study
      period was 17.4% in the intervention group versus 56.5% in the standard aftercare
      group (p = 0.013). Only the intervention group achieved their pre-agreed levels
      of adherence, disease-specific quality of life, and return to employment. This
      comparative effectiveness study provides the basis for multicenter study testing
      of telemedically supported case management with the aim of optimizing
      posttransplant aftercare. The trial was registered with the German Clinical
      Trials Register (www.DRKS.de), DKRS00007634.

PMID- 27873479
TI  - Cytokine and chemokine tear levels in patients with uveitis.
AB  - PURPOSE: To determine whether the levels of cytokines and chemokines in tears
      differ in uveitis patients and healthy subjects. METHODS: Ninety-two uveitis
      patients (mean age 46.4 years) and 157 control healthy subjects (mean age 49.5
      years) were recruited. Subjects with ocular surface diseases such as dry eye were
      excluded from the study. Using multiplex bead-based assays, tears (4 MUl) were
      analysed for the concentration of interleukin (IL)-1beta, IL-1RA, IL-2, IL-6, IL
      7, IL-8/CXCL8, IL-10, IL-12p70, IL-15, IL-17A, IL-23, epidermal growth factor
      (EGF), fractalkine/CX3CL1, interferon-gamma, IP-10/CXCL10, monocyte chemo
      attractant protein (MCP)-1/CCL2, tumour necrosis factor-alpha, vascular
      endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, TGF
      beta2 and TGF-beta3. Tear molecule levels were compared between the groups and
      among the different forms of uveitis and disease severity. RESULTS: Epidermal
      growth factor, IL-1RA, IL-7, IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, TGF-beta2 and
      VEGF were detected in more than 75% of the samples in both groups. Statistically
      significant differences in percentage of detection between control and patient
      groups were found for IL-23, IL-1beta, IL-15, EGF, fractalkine/CX3CL1 and MCP
      1/CCL2. The concentrations of IL-1RA, IL-8/CXCL8, fractalkine/CX3CL1, IP
      10/CXCL10, VEGF and TGF-beta2 in uveitis tear samples were elevated compared to
      controls (p < 0.05). Significant differences in tear levels of those molecules
      and also EGF were also present depending on the anatomic classification of
      uveitis. CONCLUSION: There were significant differences in the levels of several
      cytokines and chemokines in tears of patients with uveitis compared with healthy
      subjects. These results can help understand the underlying pathophysiology of the
      uveitis and could potentially aid in diagnosis.

PMID- 27873480
TI  - Dry-Deposited Transparent Carbon Nanotube Film as Front Electrode in Colloidal
      Quantum Dot Solar Cells.
AB  - Single-walled carbon nanotubes (SWCNTs) show great potential as an alternative
      material for front electrodes in photovoltaic applications, especially for
      flexible devices. In this work, a press-transferred transparent SWCNT film was
      utilized as front electrode for colloidal quantum dot solar cells (CQDSCs). The
      solar cells were fabricated on both glass and flexible substrates, and maximum
      power conversion efficiencies of 5.5 and 5.6 %, respectively, were achieved,
      which corresponds to 90 and 92 % of an indium-doped tin oxide (ITO)-based device
      (6.1 %). The SWCNTs are therefore a very good alternative to the ITO-based
      electrodes especially for flexible solar cells. The optical electric field
      distribution and optical losses within the devices were simulated theoretically
      and the results agree with the experimental results. With the optical simulations
      that were performed it may also be possible to enhance the photovoltaic
      performance of SWCNT-based solar cells even further by optimizing the device
      configuration or by using additional optical active layers, thus reducing light
      reflection of the device and increasing light absorption in the quantum dot
      layer.

PMID- 27873481
TI  - A case of pulmonary cryptococcosis with large pericardial effusion diagnosed
      using cervical lymph node biopsy.
AB  - Pulmonary cryptococcosis (PC) is a relatively rare infectious disease. It mainly
      involves the lungs; however, in some patients, the infection could spread to
      other parts of the body. PC mostly occurs in patients with immune deficiencies.
      However, PC infections have been reported in non-immunocompromised patients. The
      diagnosis of PC is challenging in patients without immune deficiencies. Here, the
      case of a 27-year-old immunocompetent woman who was diagnosed with PC was report.
      She had unexplained fever and a history of close contact with poultry feathers.
      Lesions were observed in the lungs, pleural cavity, pericardium, and cervical
      lymph nodes. Biopsy of the cervical lymph nodes helped in the pathological
      diagnosis of PC. She was treated with fluconazole, and the lesions disappeared.
      They present this case to encourage detailed inquiry of medical history in such
      patients, improve the diagnostic awareness of clinicians, and help reduce the
      likelihood of misdiagnosis.

PMID- 27873482
TI  - Incorporating evolutionary adaptation in species distribution modelling reduces
      projected vulnerability to climate change.
AB  - Based on the sensitivity of species to ongoing climate change, and numerous
      challenges they face tracking suitable conditions, there is growing interest in
      species' capacity to adapt to climatic stress. Here, we develop and apply a new
      generic modelling approach (AdaptR) that incorporates adaptive capacity through
      physiological limits, phenotypic plasticity, evolutionary adaptation and
      dispersal into a species distribution modelling framework. Using AdaptR to
      predict change in the distribution of 17 species of Australian fruit flies
      (Drosophilidae), we show that accounting for adaptive capacity reduces projected
      range losses by up to 33% by 2105. We identify where local adaptation is likely
      to occur and apply sensitivity analyses to identify the critical factors of
      interest when parameters are uncertain. Our study suggests some species could be
      less vulnerable than previously thought, and indicates that spatiotemporal
      adaptive models could help improve management interventions that support
      increased species' resilience to climate change.

PMID- 27873483
TI  - Successful Lung Transplantation From Hepatitis C Positive Donor to Seronegative
      Recipient.
AB  - Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative
      recipients is not currently performed due to the very high risk of transmission.
      Previous reports have shown poor survival when this practice was applied. The
      emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of
      sustained virologic response in immunocompetent patients. We report here
      successful transplantation of lungs from HCV+ donor to HCV- recipient. The
      recipient was an HCV- patient with chronic lung allograft dysfunction. Viral
      transmission occurred early posttransplant but excellent clinical outcomes were
      observed including elimination of HCV after 12 weeks of treatment using DAAs.

PMID- 27873485
TI  - Dunn's effect over Brazilian proteomics.

PMID- 27873484
TI  - Pregnant women's perceptions of gestational weight gain: A systematic review and
      meta-synthesis of qualitative research.
AB  - Excess gestational weight gain has numerous negative health outcomes for women
      and children, including high blood pressure, diabetes, and cesarean section
      (maternal) and high birth weight, trauma at birth, and asphyxia (infants). Excess
      weight gain in pregnancy is associated with a higher risk of long-term obesity in
      both mothers and children. Despite a concerted public health effort, the
      proportion of pregnant women gaining weight in excess of national guidelines
      continues to increase. To understand this phenomenon and offer suggestions for
      improving interventions, we conducted a systematic review of qualitative research
      on pregnant women's perceptions and experiences of weight gain in pregnancy. We
      used the methodology of qualitative meta-synthesis to analyze 42 empirical
      qualitative research studies conducted in high-income countries and published
      between 2005 and 2015. With this synthesis, we provide an account of the
      underlying factors and circumstances (barriers, facilitators, and motivators)
      that pregnant women identify as important for appropriate weight gain. We also
      offer a description of the strategies identified by pregnant women as acceptable
      and appropriate ways to promote healthy weight gain. Through our integrative
      analysis, we identify women's common perception on the struggle to enact health
      behaviors and physical, social, and environmental factors outside of their
      control. Effective and sensitive interventions to encourage healthy weight gain
      in pregnancy must consider the social environment in which decisions about weight
      take place.

PMID- 27873486
TI  - On life after Proteomics.

PMID- 27873487
TI  - Mike Dunn: Proteomics in Spain, and the field of plant proteomics.

PMID- 27873488
TI  - The role of microbiota in compensatory growth of protein-restricted rats.
AB  - Compensatory growth is a physiological phenomenon found in both humans and
      animals. However, the underlying mechanisms are unclear. In this study, for the
      first time, we investigated the role of microbiota in compensatory growth induced
      by protein restriction using a rat model. Weaned Sprague-Dawley rats were fed a
      low protein diet (L group), a normal protein diet (N group) and a low protein
      diet for 2 weeks followed by a normal protein diet (LN group). The results showed
      that in contrast with the inhibited growth of rats in the L group, compensatory
      growth was observed in the LN group. Meanwhile, rats in the LN group had
      increased concentrations of total short chain fatty acids, particularly butyrate,
      and an altered bacterial composition with modified abundances of
      Peptostreptococcaceae, Bifidobacteriaceae, Porphyromonadaceae and Prevotellaceae
      in the colonic content. Furthermore, gene expression analysis indicated that the
      rats that experienced compensatory growth had improved barrier function and
      innate immune function in the colon. Our data revealed the importance of colonic
      microbiota in achieving compensatory growth.

PMID- 27873489
TI  - A Review of Modeling Approaches to Predict Drug Response in Clinical Oncology.
AB  - Model-based approaches have emerged as important tools for quantitatively
      understanding temporal relationships between drug dose, concentration, and effect
      over the course of treatment, and have now become central to optimal drug
      development and tailored drug treatment. In oncology, the therapeutic index of a
      chemotherapeutic drug is typically narrow and a full dose-response relationship
      is not available, often because of treatment failure. Noting the benefits of
      model-based approaches and the low therapeutic index of oncology drugs, in recent
      years, modeling approaches have been increasingly used to streamline oncologic
      drug development through early identification and quantification of dose-response
      relationships. With this background, this report reviews publications that used
      model-based approaches to evaluate drug treatment outcome variables in oncology
      therapeutics, ranging from tumor size dynamics to tumor/biomarker time courses
      and survival response.

PMID- 27873490
TI  - EGF Induced RET Inhibitor Resistance in CCDC6-RET Lung Cancer Cells.
AB  - PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET)
      has been newly identified potential driver mutation in lung adenocarcinoma.
      Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase
      activity, which suggests that patients with RET fusion genes may be treatable
      with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these
      agents remain largely unknown. Thus, the present study aimed to determine whether
      epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET
      inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND
      METHODS: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung
      cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib)
      were examined. RESULTS: CCDC6-RET lung cancer cells were highly sensitive to RET
      inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered
      resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass
      survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib)
      resensitized cancer cells to RET inhibitors, even in the presence of EGF.
      Endothelial cells, which are known to produce EGF, decreased the sensitivity of
      CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by
      EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI
      (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors.
      CONCLUSION: EGF could trigger resistance to RET inhibition in CCDC6-RET lung
      cancer cells, and endothelial cells may confer resistance to RET inhibitors by
      EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the
      treatment of RET-positive lung cancer patients.

PMID- 27873491
TI  - Detection of Circulating Tumor Cells in Breast Cancer Patients Using Cytokeratin
      19 Real-Time RT-PCR.
AB  - PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic
      factors, as well as key mediators in the metastatic cascade, have been
      investigated. This study aimed to validate a method to quantify CTCs in
      peripheral blood using a real-time reverse transcriptase polymerase chain
      reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of
      this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS:
      Real-time monitoring PCR of fluorescently labeled specific hybridization probes
      for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors,
      69 patients with early breast cancer, 47 patients with locally advanced breast
      cancer, and 126 patients with metastatic breast cancer were prospectively
      obtained and analyzed for CTC detection. RESULTS: CK-19 mRNA was not detectable
      in healthy subjects using the real-time RT-PCR method. The detection rates of CK
      19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69),
      46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast
      cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease
      was slightly higher than early or locally advanced breast cancer; however, the
      detection rate according to disease burden was not statistically different
      (p=0.097). The detection rate was higher in patients with pleural metastasis
      (p=0.045). CTC detection was associated with poor survival (p=0.014). CONCLUSION:
      A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in
      peripheral blood in breast cancer patients can be used in further prospective
      studies to evaluate the predictive and prognostic importance of CTCs.

PMID- 27873492
TI  - Aberrant Hypomethylation of Solute Carrier Family 6 Member 12 Promoter Induces
      Metastasis of Ovarian Cancer.
AB  - PURPOSE: Ovarian cancer (OC) is the most fatal of gynecological malignancies with
      a high rate of recurrence. We aimed to evaluate the expression of solute carrier
      family 6, member 12 (SLC6A12) and methylation of its promoter CpG sites in a
      xenograft mouse model of metastatic OC, and to investigate the regulatory
      mechanisms that promote aggressive properties during OC progression. MATERIALS
      AND METHODS: Expression of SLC6A12 mRNA was determined by reverse-transcription
      quantitative polymerase chain reaction (RT-qPCR), and DNA methylation status of
      its promoter CpGs was detected by quantitative methylation-specific PCR. The
      metastatic potential of SLC6A12 was evaluated by in vitro migration/invasion
      transwell assays. Gene expression and DNA methylation of SLC6A12 and clinical
      outcomes were further investigated from publicly available databases from
      curatedOvarianData and The Cancer Genome Atlas. RESULTS: SLC6A12 expression was
      8.1-14.0-fold upregulated and its DNA methylation of promoter CpG sites was 41
      62% decreased in tumor metastases. After treatment with DNA methyltransferase
      inhibitor and/or histone deacetylase inhibitor, the expression of SLC6A12 was
      profoundly enhanced (~8.0-fold), strongly supporting DNA methylation-dependent
      epigenetic regulation of SLC6A12. Overexpression of SLC6A12 led to increased
      migration and invasion of ovarian carcinoma cells in vitro, approximately 2.0
      fold and 3.3-fold, respectively. The meta-analysis showed that high expression of
      SLC6A12 was significantly associated with poor overall survival [hazard ratio
      (HR)=1.07, p value=0.016] and that low DNA methylation levels of SLC6A12 at
      specific promoter CpG site negatively affected patient survival. CONCLUSION: Our
      findings provide novel evidence for the biological and clinical significance of
      SLC6A12 as a metastasis-promoting gene.

PMID- 27873494
TI  - Identificaiton of Novel Immunogenic Human Papillomavirus Type 16 E7-Specific
      Epitopes Restricted to HLA-A*33;03 for Cervical Cancer Immunotherapy.
AB  - PURPOSE: To identify new immunogenic HLA-A*33;03-restricted epitopes from the
      human papillomavirus (HPV) 16 E7 protein for immunotherapy against cervical
      cancer. MATERIALS AND METHODS: We synthesized fourteen overlapping 15-amino acid
      peptides and measured intracellular interferon-gamma (IFN-gamma) production in
      PBMC and CD8+ cytotoxic T lymphocytes (CTLs) after sensitization with these
      peptides using flow cytometry and ELISpot assay. The immunogenicity of epitopes
      was verified using a 51Cr release assay with SNU1299 cells. RESULTS: Among the
      fourteen 15-amino acid peptides, E749-63 (RAHYNIVTFCCKCDS) demonstrated the
      highest IFN-gamma production from peripheral blood mononuclear cells (PBMCs), and
      CD8+ CTLs sensitized with E749-63 showed higher cytotoxic effect against SNU1299
      cells than did CD8+ CTLs sensitized with other peptides or a negative control
      group. Thirteen 9- or 10-amino acid overlapping peptides spanning E749-63, E750
      59 (AHYNIVTFCC), and E752-61 (YNIVTFCCKC) induced significantly higher IFN-gamma
      production and cytotoxic effects against SNU1299 cells than the other peptides
      and negative controls, and the cytotoxicity of E750-59- and E752-61-sensitized
      PBMCs was induced via the cytolytic effect of CD8+ CTLs. CONCLUSION: We
      identified E750-59 and E752-61 as novel HPV 16 E7 epitopes for HLA-A*33;03. CD8+
      CTL sensitized with these peptides result in an antitumor effect against cervical
      cancer cells. These epitopes could be useful for immune monitoring and
      immunotherapy for cervical cancer and HPV 16-related diseases including anal
      cancer and oropharyngeal cancer.

PMID- 27873493
TI  - Decitabine as a First-Line Treatment for Older Adults Newly Diagnosed with Acute
      Myeloid Leukemia.
AB  - PURPOSE: Decitabine, a DNA hypomethylating agent, was recently approved for use
      in Korea for older adults with acute myeloid leukemia (AML) who are not
      candidates for standard chemotherapy. This study aimed to evaluate the role of
      decitabine as a first-line treatment for older adults with AML. MATERIALS AND
      METHODS: Twenty-four patients with AML who received at least one course of
      decitabine (20 mg/m2/d intravenously for 5 days every 4 weeks) as a first-line
      therapy at Severance Hospital were evaluated retrospectively. RESULTS: The median
      age of the patients was 73.5 years. The longest follow-up duration was 502 days.
      A total of 113 cycles of treatment were given to 24 patients, and the median
      number of cycles was four (range, 1-14). Thirteen patients dropped out because of
      death, no or loss of response, patient refusal, or transfer to another hospital.
      Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles,
      respectively, and responses to treatment were evaluated in 17. A complete
      response (CR) or CR with incomplete blood-count recovery was achieved in six
      (35.3%) patients, and the estimated median overall survival was 502 days. Ten
      patients developed grade >2 hematologic or non-hematologic toxicities. In
      univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin
      level, and bone marrow iron were significantly associated with response to
      decitabine. CONCLUSION: Five-day decitabine treatment showed acceptable efficacy
      in older patients with AML who are unfit for conventional chemotherapy, with a CR
      rate 35.3% and about a median overall survival of 18 months.

PMID- 27873495
TI  - The Effectiveness of Ferritin as a Contrast Agent for Cell Tracking MRI in Mouse
      Cancer Models.
AB  - PURPOSE: We aimed to investigate the effectiveness of ferritin as a contrast
      agent and a potential reporter gene for tracking tumor cells or macrophages in
      mouse cancer models. MATERIALS AND METHODS: Adenoviral human ferritin heavy chain
      (Ad-hFTH) was administrated to orthotopic glioma models and subcutaneous colon
      cancer mouse models using U87MG and HCT116 cells, respectively. Brain MR images
      were acquired before and daily for up to 6 days after the intracranial injection
      of Ad-hFTH. In the HCT116 tumor model, MR examinations were performed before and
      at 6, 24, and 48 h after intratumoral injection of Ad-hFTH, as well as before and
      every two days after intravenous injection of ferritin-labeled macrophages. The
      contrast effect of ferritin in vitro was measured by MR imaging of cell pellets.
      MRI examinations using a 7T MR scanner comprised a T1-weighted (T1w) spin-echo
      sequence, T2-weighted (T2w) relaxation enhancement sequence, and T2*-weighted
      (T2*w) fast low angle shot sequence. RESULTS: Cell pellet imaging of Ad-hFTH in
      vitro showed a strong negatively enhanced contrast in T2w and T2*w images,
      presenting with darker signal intensity in high concentrations of Fe. T2w images
      of glioma and subcutaneous HCT116 tumor models showed a dark signal intensity
      around or within the Ad-hFTH tumor, which was distinct with time and apparent in
      T2*w images. After injection of ferritin-labeled macrophages, negative contrast
      enhancement was identified within the tumor. CONCLUSION: Ferritin could be a good
      candidate as an endogenous MR contrast agent and a potential reporter gene that
      is capable of maintaining cell labeling stability and cellular safety.

PMID- 27873496
TI  - Ovarian Clear Cell Carcinoma Sub-Typing by ARID1A Expression.
AB  - PURPOSE: Loss of AT-rich DNA-interacting domain 1A (ARID1A) has been identified
      as a driving mutation of ovarian clear cell carcinoma (O-CCC), a triple-negative
      ovarian cancer that is intermediary between serous and endometrioid subtypes, in
      regards to molecular and clinical behaviors. However, about half of O-CCCs still
      express BAF250a, the protein encoded by ARID1A. Herein, we aimed to identify
      signatures of ARID1A-positive O-CCC in comparison with its ARID1A-negative
      counterpart. MATERIALS AND METHODS: Seventy cases of O-CCC were included in this
      study. Histologic grades and patterns of primary tumor, molecular marker
      immunohistochemistry profiles, and clinical outcomes were analyzed. RESULTS:
      Forty-eight (69%) O-CCCs did not express BAF250a, which were designated as
      "ARID1A-negative." The other 22 (31%) O-CCCs were designated as "ARID1A
      positive." ARID1A-positive tumors were more likely to be histologically of high
      grades (41% vs. 10%, p=0.003), ERbeta-positive (45% vs. 17%, p=0.011), and less
      likely to be HNF1beta-positive (77% vs. 96%, p=0.016) and E-cadherin-positive
      (59% vs. 83%, p=0.028) than ARID1A-negative tumors. Patient age, parity, tumor
      stage were not significantly different in between the two groups. Cancer-specific
      survival was not significantly different either. CONCLUSION: We classified O-CCCs
      according to ARID1A expression status. ARID1A-positive O-CCCs exhibited distinct
      immunohistochemical features from ARID1A-negative tumors, suggesting a different
      underlying molecular event during carcinogenesis.

PMID- 27873497
TI  - High Prevalence and Clinical Implication of Myocardial Bridging in Patients with
      Early Repolarization.
AB  - PURPOSE: Recent evidence suggests that early repolarization (ER) is related with
      myocardial ischemia. Compression of coronary artery by a myocardial bridging (MB)
      can be associated with clinical manifestations of myocardial ischemia. This study
      aimed to evaluate the associations of MB in patients with ER. MATERIALS AND
      METHODS: In consecutive patients (n=1303, age, 61+/-12 years) who had undergone
      coronary angiography, we assessed the prevalence and prognostic implication of MB
      in those with ER (n=142) and those without ER (n=1161). RESULTS: MB was observed
      in 54 (38%) and 196 (17%) patients in ER and no-ER groups (p<0.001). In
      multivariate analysis, MB was independently associated with ER (odd ratio: 2.9,
      95% confidence interval: 1.98-4.24, p<0.001). Notched type ER was more frequently
      observed in MB involving the mid portion of left anterior descending coronary
      artery (LAD) (69.8% vs. 30.2%, p=0.03). Cardiac event was observed in nine (6.3%)
      and 22 (1.9%) subjects with and without ER, respectively. MB was more frequently
      observed in sudden death patients with ER (2 out of 9, 22%) than in those without
      ER (0 out of 22). CONCLUSION: MB was independently associated with ER in patients
      without out structural heart disease who underwent coronary angiography. Notched
      type ER was closely related with MB involving the mid portion of the LAD. Among
      patients who had experienced cardiac events, a higher prevalence of MB was
      observed in patients with ER than those without ER. Further prospective studies
      on the prognosis of MB in ER patients are required.

PMID- 27873498
TI  - The Impact of Diabetes Mellitus on Vascular Biomarkers in Patients with End-Stage
      Renal Disease.
AB  - PURPOSE: Diabetes mellitus (DM) is the most common cause of end-stage renal
      disease (ESRD) and an important risk factor for cardiovascular (CV) disease. We
      investigated the impact of DM on subclinical CV damage by comprehensive screening
      protocol in ESRD patients. MATERIALS AND METHODS: Echocardiography, coronary
      computed tomography angiogram, 24-h ambulatory blood pressure monitoring, and
      central blood pressure with pulse wave velocity (PWV) were performed in 91 ESRD
      patients from the Cardiovascular and Metabolic disease Etiology Research Center
      HIgh risk cohort. RESULTS: The DM group (n=38) had higher systolic blood pressure
      than the non-DM group (n=53), however, other clinical CV risk factors were not
      different between two groups. Central aortic systolic pressure (148.7+/-29.8 mm
      Hg vs. 133.7+/-27.0 mm Hg, p= 0.014), PWV (12.1+/-2.7 m/s vs. 9.4+/-2.1 m/s,
      p<0.001), and early mitral inflow to early mitral annulus velocity (16.7+/-6.4
      vs. 13.7+/-5.9, p=0.026) were higher in the DM group. Although the prevalence of
      coronary artery disease (CAD) was not different between the DM and the non-DM
      group (95% vs. 84.4%, p=0.471), the severity of CAD was higher in the DM group
      (p=0.01). In multivariate regression analysis, DM was an independent determinant
      for central systolic pressure (p=0.011), PWV (p<0.001) and the prevalence of CAD
      (p=0.046). CONCLUSION: Diabetic ESRD patients have higher central systolic
      pressure and more advanced arteriosclerosis than the non-DM control group. These
      findings suggest that screening for subclinical CV damage may be helpful for
      diabetic ESRD patients.

PMID- 27873499
TI  - Assessment of Coronary Artery Calcium Scoring for Statin Treatment Strategy
      according to ACC/AHA Guidelines in Asymptomatic Korean Adults.
AB  - PURPOSE: The 2013 American College of Cardiology (ACC)/American Heart Association
      (AHA) cholesterol management guidelines advocate the use of statin treatment for
      prevention of cardiovascular disease. We aimed to assess the usefulness of
      coronary artery calcium (CAC) for stratifying potential candidates of statin use
      among asymptomatic Korean individuals. MATERIALS AND METHODS: A total of 31375
      subjects who underwent CAC scoring as part of a general health examination were
      enrolled in the current study. Statin eligibility was categorized as statin
      recommended (SR), considered (SC), and not recommended (SN) according to ACC/AHA
      guidelines. Cox regression analysis was employed to estimate hazard ratios (HR)
      with 95% confidential intervals (CI) after stratifying the subjects according to
      CAC scores of 0, 1-100, and >100. Number needed to treat (NNT) to prevent one
      mortality event during study follow up was calculated for each group. RESULTS:
      Mean age was 54.4+/-7.5 years, and 76.3% were male. During a 5-year median follow
      up (interquartile range; 3-7), there were 251 (0.8%) deaths from all-causes. A
      CAC >100 was independently associated with mortality across each statin group
      after adjusting for cardiac risk factors (e.g., SR: HR, 1.60; 95% CI, 1.07-2.38;
      SC: HR, 2.98; 95% CI, 1.09-8.13, and SN: HR, 3.14; 95% CI, 1.08-9.17). Notably,
      patients with CAC >100 displayed a lower NNT in comparison to the absence of CAC
      or CAC 1-100 in SC and SN groups. CONCLUSION: In Korean asymptomatic individuals,
      CAC scoring might prove useful for reclassifying patient eligibility for
      receiving statin therapy based on updated 2013 ACC/AHA guidelines.

PMID- 27873500
TI  - Impact of Diltiazem Alone versus Diltiazem with Nitrate on Five-Year Clinical
      Outcomes in Patients with Significant Coronary Artery Spasm.
AB  - PURPOSE: Calcium channel blockers diltiazem and nitrate have been used as
      selective coronary vasodilators for patients with significant coronary artery
      spasm (CAS). However, no study has compared the efficacy of diltiazem alone
      versus diltiazem with nitrate for long-term clinical outcomes in patients with
      CAS. MATERIALS AND METHODS: A total of 2741 consecutive patients without
      significant coronary artery disease with positive CAS by acetylcholine (Ach)
      provocation test between November 2004 and May 2014 were enrolled. Significant
      CAS was defined as a narrowing of >70% by incremental intracoronary injection of
      20, 50, and 100 MUg of Ach into the left coronary artery. Patients were assigned
      to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate,
      n=1899) at physician discretion. To adjust for potential confounders, a
      propensity score matching (PSM) analysis was performed using the logistic
      regression model. After PSM analysis, two well-balanced groups (811 pairs,
      n=1622, C-statistic=0.708) were generated. RESULTS: At 5 years, there were
      similar incidences in primary endpoints, including mortality, myocardial
      infarction, revascularization, and recurrent angina requiring repeat coronary
      angiography between the two groups. Diltiazem alone was not an independent
      predictor for major adverse cardiovascular events or recurrent angina requiring
      repeat coronary angiography. CONCLUSION: Despite the expected improvement of
      endothelial function and the relief of CAS, the combination of diltiazem and
      nitrate treatment was not superior to diltiazem alone in reducing mortality and
      cardiovascular events up to 5 years in patients with significant CAS.

PMID- 27873501
TI  - A Comparison of Peri-Procedural Myocardial Infarction between Paclitaxel-Coated
      Balloon and Drug-Eluting Stent on De Novo Coronary Lesions.
AB  - PURPOSE: This study compared the impact of paclitaxel-coated balloons (PCB) or
      drug eluting stents (DES) on peri-procedural myocardial infarction (PMI) on de
      novo coronary lesion in stable patients. MATERIALS AND METHODS: In this
      observational study, we compared the incidence of PMI amongst patients with
      single vessel de novo coronary lesions who underwent treatment with a PCB or DES.
      Propensity score-matching analysis was used to assemble a cohort of patients with
      similar baseline characteristics. PMI was classified as myocardial infarction
      occurring within 48 hours after percutaneous coronary intervention with a
      threshold of 5 x the 99th percentile upper reference limit of normal for creatine
      kinase-myocardial band (CK-MB) or troponin T (TnT). RESULTS: One hundred four
      patients (52 receiving PCB and 52 receiving DES) were enrolled in this study. The
      peak mean values of CK-MB and TnT were significantly higher in the DES group.
      There was a significantly higher rate of PMI in the DES group (23.1% vs. 1.9%,
      p=0.002). Total occlusion of the side-branch occurred in two patients treated
      with DES, while no patients treated with PCB. In multivariable analysis, DES was
      the only independent predictor of PMI compared with PCB (odds ratio 42.85, 95%
      confidence interval: 3.44-533.87, p=0.004). CONCLUSION: Treatment with a PCB on
      de novo coronary lesion might be associated with a significant reduction in the
      risk of PMI compared to DES.

PMID- 27873503
TI  - Increased Risk of Cardiovascular Events in Stroke Patients Who had Not Undergone
      Evaluation for Coronary Artery Disease.
AB  - PURPOSE: Although asymptomatic coronary artery occlusive disease is common in
      stroke patients, the long-term advantages of undergoing evaluation for coronary
      arterial disease using multi-detector coronary computed tomography (MDCT) have
      not been well established in stroke patients. We compared long-term cardio
      cerebrovascular outcomes between patients who underwent MDCT and those who did
      not. MATERIALS AND METHODS: This was a retrospective study in a prospective
      cohort of consecutive ischemic stroke patients. Of the 3117 patients who were
      registered between July 2006 and December 2012, MDCT was performed in 1842
      patients [MDCT (+) group] and not in 1275 patients [MDCT (-) group]. Occurrences
      of death, cardiovascular events, and recurrent stroke were compared between the
      groups using Cox proportional hazards models and propensity score analyses.
      RESULTS: During the mean follow-up of 38.0+/-24.8 months, 486 (15.6%) patients
      died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred
      in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%),
      cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%)
      were higher in the MDCT (-) group than in the MDCT (+) group. The Cox
      proportional hazards model and the five propensity score-adjusted models
      consistently demonstrated that the MDCT (-) group was at a high risk of
      cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172-8.735
      in 1:1 propensity matching analysis) as well as death. The MDCT (-) group seemed
      to also have a higher risk of recurrent stroke. CONCLUSION: Acute stroke patients
      who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent
      strokes during follow-up.

PMID- 27873502
TI  - Efficacy and Safety of Intravenous Urapidil for Older Hypertensive Patients with
      Acute Heart Failure: A Multicenter Randomized Controlled Trial.
AB  - PURPOSE: Urapidil is putatively effective for patients with hypertension and
      acute heart failure, although randomized controlled trials thereon are lacking.
      We investigated the efficacy and safety of intravenous urapidil relative to that
      of nitroglycerin in older patients with hypertension and heart failure in a
      randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with
      hypertension and heart failure were randomly assigned to receive intravenous
      urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters,
      cardiac function, and safety outcomes were compared. RESULTS: Patients in the
      urapidil group had significantly lower mean systolic blood pressure (110.1+/-6.5
      mm Hg) than those given nitroglycerin (126.4+/-8.1 mm Hg, p=0.022), without
      changes in heart rate. Urapidil was associated with improved cardiac function as
      reflected by lower N terminal-pro B type natriuretic peptide after 7 days
      (3311.4+/-546.1 ng/mL vs. 4879.1+/-325.7 ng/mL, p=0.027) and improved left
      ventricular ejection fraction (62.2+/-3.4% vs. 51.0+/-2.4%, p=0.032). Patients
      given urapidil had fewer associated adverse events, specifically headache
      (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all
      cause mortality rates were similar. CONCLUSION: Intravenous administration of
      urapidil, compared with nitroglycerin, was associated with better control of
      blood pressure and preserved cardiac function, as well as fewer adverse events,
      for elderly patients with hypertension and acute heart failure.

PMID- 27873504
TI  - Lenticulostriate Artery Involvement is Predictive of Poor Outcomes in Superficial
      Middle Cerebral Artery Territory Infarction.
AB  - PURPOSE: Patients with superficial middle cerebral artery (MCA) territory
      infarction may have concomitant lenticulostriate artery (LSA) territory
      infarction. We investigated the mechanisms thereof and the outcomes of patients
      with superficial MCA territory infarction according to the presence or absence of
      LSA involvement. MATERIALS AND METHODS: Consecutive patients with first-ever
      infarction in the unilateral superficial MCA territory were included in this
      study. They were divided into the superficial MCA only (SM) group and the
      superficial MCA plus LSA (SM+L) group. RESULTS: Of the 398 patients, 84 patients
      (21.1%) had LSA involvement (SM+L group). The SM+L group more frequently had
      significant stenosis of the proximal MCA or carotid artery and high-risk
      cardioembolic sources. Stroke severity and outcomes were remarkably different
      between the groups. The SM+L group showed more severe neurologic deficits
      (National Institute of Health Stroke Scale score 10.8+/-7.1 vs. 4.0+/-5.0,
      p<0.001) and larger infarct in the superficial MCA territory (40.8+/-62.6 cm3 vs.
      10.8+/-21.8 cm3, p<0.001) than the SM group. A poor functional outcome (mRS >2)
      at 3 months was more common in the SM+L group (64.3% vs. 15.9%, p<0.001). During
      a mean follow-up of 26 months, 67 patients died. All-cause (hazard ratio, 2.246)
      and stroke (hazard ratio, 9.193) mortalities were higher in the SM+L group than
      the SM group. In multivariate analyses, LSA involvement was an independent
      predictor of poor functional outcomes and stroke mortality. CONCLUSION: LSA
      territory involvement is predictive of poor long-term outcomes in patients with
      superficial MCA territory infarction.

PMID- 27873506
TI  - Development of a Robotic Colonoscopic Manipulation System, Using Haptic Feedback
      Algorithm.
AB  - PURPOSE: Colonoscopy is one of the most effective diagnostic and therapeutic
      tools for colorectal diseases. We aim to propose a master-slave robotic
      colonoscopy that is controllable in remote site using conventional colonoscopy.
      MATERIALS AND METHODS: The master and slave robot were developed to use
      conventional flexible colonoscopy. The robotic colonoscopic procedure was
      performed using a colonoscope training model by one expert endoscopist and two
      unexperienced engineers. To provide the haptic sensation, the insertion force and
      the rotating torque were measured and sent to the master robot. RESULTS: A slave
      robot was developed to hold the colonoscopy and its knob, and perform insertion,
      rotation, and two tilting motions of colonoscope. A master robot was designed to
      teach motions of the slave robot. These measured force and torque were scaled
      down by one tenth to provide the operator with some reflection force and torque
      at the haptic device. The haptic sensation and feedback system was successful and
      helpful to feel the constrained force or torque in colon. The insertion time
      using robotic system decreased with repeated procedures. CONCLUSION: This work
      proposed a robotic approach for colonoscopy using haptic feedback algorithm, and
      this robotic device would effectively perform colonoscopy with reduced burden and
      comparable safety for patients in remote site.

PMID- 27873505
TI  - Hyperbaric Oxygen Pretreatment Improves Cognition and Reduces Hippocampal Damage
      Via p38 Mitogen-Activated Protein Kinase in a Rat Model.
AB  - PURPOSE: To investigate the effects of hyperbaric oxygen (HBO) pretreatment on
      cognitive decline and neuronal damage in an Alzheimer's disease (AD) rat model.
      MATERIALS AND METHODS: Rats were divided into three groups: normal saline (NS),
      AD, and HBO+AD. In the AD group, amyloid beta peptide (Abeta)1-40 was injected
      into the hippocampal CA1 region of the brain. NS rats received NS injection. In
      the HBO+AD group, rats received 5 days of daily HBO therapy following Abeta1-40
      injection. Learning and memory capabilities were examined using the Morris water
      maze task. Neuronal damage and astrocyte activation were evaluated by hematoxylin
      eosin staining and immunohistochemistry, respectively. Dendritic spine density
      was determined by Golgi-Cox staining. Tumor necrosis factor-alpha, interleukin
      1beta, and interleukin-10 production was assessed by enzyme-linked immunosorbent
      assay. Neuron apoptosis was evaluated by terminal deoxynucleotidyl transferase
      dUTP nick end labeling. Protein expression was examined by western blotting.
      RESULTS: Learning and memory dysfunction was ameliorated in the HBO+AD group, as
      shown by significantly lower swimming distances and escape latency, compared to
      the AD group. Lower rates of neuronal damage, astrocyte activation, dendritic
      spine loss, and hippocampal neuron apoptosis were seen in the HBO+AD than in the
      AD group. A lower rate of hippocampal p38 mitogen-activated protein kinase (MAPK)
      phosphorylation was observed in the HBO+AD than in the AD group. CONCLUSION: HBO
      pretreatment improves cognition and reduces hippocampal damage via p38 MAPK in AD
      rats.

PMID- 27873507
TI  - Clinical Efficacy of Beclomethasone Dipropionate in Korean Patients with
      Ulcerative Colitis.
AB  - PURPOSE: Our aim was to evaluate the efficacy and safety of oral beclomethasone
      dipropionate (BDP) in Korean patients with ulcerative colitis (UC). MATERIALS AND
      METHODS: The medical records of patients with active UC who were treated with BDP
      were retrospectively reviewed. Partial Mayo Clinic score (pMS) was calculated to
      determine disease activity. After 4 weeks of therapy, clinical remission,
      clinical response, and response failure rates were evaluated. Clinical remission
      was defined as a post-treatment pMS of 0 or 1, clinical response as a decrease of
      two of three points in pMS and >30% from baseline, and response failure as a lack
      of clinical response. Also, we considered that clinical remission was included in
      clinical response. RESULTS: Between July 2013 and April 2015, 95 patients with UC
      received BDP therapy at our institution (median age, 44 years; range, 12-81
      years). After 4 weeks of therapy, clinical remission and clinical response rates
      were 50.5% and 73.7%, respectively. Mean change of pMS before and after BDP
      therapy was 2.4. There was no significant side effect reported. In multivariate
      analysis, disease activity was the only factor associated with a favorable
      response. Clinical remission rate was significantly higher in the mild disease
      activity group (66.7%) than that in the moderate or severe disease activity group
      (41.9%) (p=0.024). CONCLUSION: BDP is efficacious in inducing a clinical response
      or remission in Korean patients with UC. Patients with mild UC were more likely
      to be in remission than those with moderate or severe UC after receiving BDP for
      4 weeks. BDP exhibited a good safety profile.

PMID- 27873508
TI  - Are Hemorrhoids Associated with False-Positive Fecal Immunochemical Test Results?
AB  - PURPOSE: False-positive (FP) results of fecal immunochemical tests (FITs)
      conducted in colorectal cancer (CRC) screening could lead to performing
      unnecessary colonoscopies. Hemorrhoids are a possible cause of FP FIT results;
      however, studies on this topic are extremely rare. We investigated whether
      hemorrhoids are associated with FP FIT results. MATERIALS AND METHODS: A
      retrospective study was conducted at a university hospital in Korea from June
      2013 to May 2015. Of the 34547 individuals who underwent FITs, 3946 aged >=50
      years who underwent colonoscopies were analyzed. Logistic regression analysis was
      performed to determine factors associated with FP FIT results. RESULTS: Among
      3946 participants, 704 (17.8%) showed positive FIT results and 1303 (33.0%) had
      hemorrhoids. Of the 704 participants with positive FIT results, 165 had advanced
      colorectal neoplasia (ACRN) and 539 had no ACRN (FP results). Of the 1303
      participants with hemorrhoids, 291 showed FP results, of whom 81 showed FP
      results because of hemorrhoids only. Participants with hemorrhoids had a higher
      rate of FP results than those without hemorrhoids (291/1176, 24.7% vs. 248/2361,
      10.5%; p<0.001). Additionally, the participants with hemorrhoids as the only
      abnormality had a higher rate of FP results than those experiencing no such
      abnormalities (81/531, 15.3% vs. 38/1173, 3.2%; p<0.001). In multivariate
      analysis, the presence of hemorrhoids was identified as an independent predictor
      of FP results (adjusted odds ratio, 2.76; 95% confidence interval, 2.24-3.40;
      p<0.001). CONCLUSION: Hemorrhoids are significantly associated with FP FIT
      results. Their presence seemed to be a non-negligible contributor of FP results
      in FIT-based CRC screening programs.

PMID- 27873509
TI  - Dose-Response Relationship between Alanine Aminotransferase Levels within the
      Reference Interval and Metabolic Syndrome in Chinese Adults.
AB  - PURPOSE: Elevation in serum alanine aminotransferase (ALT) levels is a biomarker
      for metabolic syndrome (MS); however, the relationship has not been fully
      investigated within the reference interval of ALT levels. Our objective was to
      explore the relationship between serum ALT levels within the reference interval
      and MS in Chinese adults. MATERIALS AND METHODS: This cross-sectional study
      included 16028 adults, who attended routine health check-ups at Shengli Oilfield
      Central Hospital from January 2006 to March 2012. The reference interval of serum
      ALT level was defined as less than 40 U/L. Logistic regression models and
      restricted cubic spline were used to evaluate the association of ALT with MS.
      RESULTS: The prevalence of MS in the total population was 13.7% (6.4% for females
      and 18.4% for males). Multiple logistic regression showed that ALT levels were
      positively associated with MS after adjustment for potential confounding factors.
      The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI):
      2.980-7.829] in females and 3.168 (95% CI: 2.649-3.790) in males, compared with
      the ALT levels in the bottom quartile. The restricted cubic spline models
      revealed a positive non-linear dose-response relationship between ALT levels and
      the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear
      dose-response relationship in men (p for nonlinearity was 0.0659). CONCLUSION:
      Serum ALT levels within the reference interval are positively associated with MS
      in a dose-response manner. Elevated ALT levels, even within the reference
      interval, may reflect early dysmetabolic changes.

PMID- 27873510
TI  - Certain Polymorphisms in SP110 Gene Confer Susceptibility to Tuberculosis: A
      Comprehensive Review and Updated Meta-Analysis.
AB  - PURPOSE: Numerous studies have assessed the association of SP110 gene variants
      with tuberculosis (TB), but the results were inconsistent. Through a
      comprehensive review and meta-analysis, our study aimed to clarify the nature of
      genetic risks contributed by 11 polymorphisms for the development of TB.
      MATERIALS AND METHODS: Through searching PubMed, web of science, China National
      Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13
      independent studies were selected. The pooled odd ratios (ORs) along with their
      corresponding 95% confidence interval (CI) were estimated for allelic
      comparisons, additive model (homozygote comparisons; heterozygote comparisons),
      dominant model and recessive model. We also assessed the heterogeneity across the
      studies and publication bias. RESULTS: The results of combined analysis revealed
      a significantly increased risk of TB for single nucleotide polymorphism (SNP)
      rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14-1.44,
      p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84-4.38, p<0.00001;
      heterozygote comparisons: OR=1.23, 95% CI=1.05-1.43, p=0.009; dominant model:
      OR=1.32, 95% CI=1.14-1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18-4.34,
      p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared
      to be increased. Moreover, increased risk of TB was also found in Asian subgroup
      of SNP rs11556887, while decreased risk of TB appeared in large sample size
      subgroup of SNP rs1135791. No significant association was observed between other
      SNPs and the risk of TB. CONCLUSION: Our meta-analysis suggested that the variant
      of SNP rs9061 might be a risk factor for TB.

PMID- 27873511
TI  - Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract
      Infection.
AB  - PURPOSE: During the late autumn to winter season (October to December) in the
      Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen
      causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human
      coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs
      more commonly than in other years. Therefore, we sought to determine the
      epidemiology, clinical characteristics, outcomes, and severity of illnesses
      associated with HCoV infections at a single center in Korea. MATERIALS AND
      METHODS: We retrospectively identified patients with positive HCoV respiratory
      specimens between October 2014 and December 2014 who were admitted to Severance
      Children's Hospital at Yonsei University Medical Center for LRTI. Charts of the
      patients with HCoV infection were reviewed and compared with RSV infection.
      RESULTS: During the study period, HCoV was the third most common respiratory
      virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of
      children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63.
      Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV,
      resulted in bronchiolitis. Two patients required care in the intensive care unit.
      However, compared with that of RSV infection, the disease course HCoV was short.
      CONCLUSION: Infections caused by HCoVs are common, and can cause LRTIs. During an
      epidemic season, clinicians should be given special consideration thereto. When
      combined with other medical conditions, such as neurologic or cardiologic
      diseases, intensive care unit (ICU) care may be necessary.

PMID- 27873512
TI  - Antimicrobial Resistance and Clinical Outcomes in Nursing Home-Acquired
      Pneumonia, Compared to Community-Acquired Pneumonia.
AB  - PURPOSE: Patients with nursing home-acquired pneumonia (NHAP) should be treated
      as hospital-acquired pneumonia (HAP) according to guidelines published in 2005.
      However, controversy still exists on whether the high mortality of NHAP results
      from multidrug resistant pathogens or underlying disease. We aimed to outline
      differences and factors contributing to mortality between NHAP and community
      acquired pneumonia (CAP) patients. MATERIALS AND METHODS: We retrospectively
      evaluated patients aged 65 years or older with either CAP or NHAP from 2008 to
      2014. Patients with healthcare-associated pneumonia other than NHAP or HAP were
      excluded. RESULTS: Among 317 patients, 212 patients had CAP and 105 had NHAP.
      Patients with NHAP had higher mortality, more frequently used a ventilator, and
      had disease of higher severity than CAP. The incidences of aspiration, tube
      feeding, and poor functional status were higher in NHAP. Twenty three out of 54
      NHAP patients and three out of 62 CAP patients had multidrug resistant pathogens
      (p<0.001). Eleven patients with NHAP died at discharge, compared to 7 patients
      with CAP (p=0.009). However, there was no association between mortality rate and
      presence of multidrug-resistant pathogens. The number of involved lobes on chest
      X-ray [odds ratio (OR)=1.708; 95% confidence interval (CI), 1.120 to 2.605] and
      use of mechanical ventilation (OR=9.537; 95% CI, 1.635 to 55.632) were
      significantly associated with in-hospital mortality. CONCLUSION: Patients with
      NHAP had higher mortality than patients with CAP. The excess mortality among
      patients with NHAP and CAP was related to disease severity but not to the
      presence of multidrug resistant pathogens.

PMID- 27873514
TI  - Efficacy of Oxidized Regenerated Cellulose, SurgiGuard(r), in Porcine Surgery.
AB  - PURPOSE: Adequate hemostasis is important for postoperative outcomes of abdominal
      surgery. This study evaluated the hemostatic effects and accompanying
      histopathological changes of a novel oxidized regenerated cellulose,
      SurgiGuard(r), during abdominal surgery. MATERIALS AND METHODS: Ten pigs
      underwent wedge resection of the spleen (1*1 cm) and liver (1.5*1.5 cm). The
      resected surface was covered with Surgicel(r) fabric or fibril type (Group A) or
      SurgiGuard(r) fabric or fibril type (Group B). Surgicel(r) and SurgiGuard(r) were
      randomized for attachment to the resected surface by fabric type (n=5) or fibril
      type (n=5). Blood loss was measured 5, 7, and 9 min after resection. Pigs were
      necropsied 6 weeks postoperatively to evaluate gross and histopathological
      changes. RESULTS: There was no significant difference in total blood loss between
      groups [spleen fabric: Group A vs. Group B, 4.38 g (2.74-6.43) vs. 3.41 g (2.46
      4.65), p=0.436; spleen fibril: Group A vs. Group B, 3.44 g (2.82-6.07) vs. 3.60 g
      (2.03-6.09), p=0.971; liver fabric: Group A vs. Group B, 4.51 g (2.67-10.61) vs.
      6.93 g (3.09-9.95), p=0.796; liver fibril: Group A vs. Group B, 3.32 g (2.50
      8.78) vs. 3.70 g (2.32-5.84), p=0.971]. Histopathological analysis revealed no
      significant difference in toxicities related to Surgicel(r) or SurgiGuard(r)
      [inflammation, fibrosis, foreign bodies, and hemorrhage (spleen: p=0.333, 0.127,
      0.751, and 1.000; liver: p=0.155, 0.751, 1.000, and 1.000, respectively)].
      CONCLUSION: SurgiGuard(r) is as effective and non-toxic as Surgicel(r) in
      achieving hemostasis after porcine abdominal surgery.

PMID- 27873513
TI  - Costs Attributable to Overweight and Obesity in Working Asthma Patients in the
      United States.
AB  - PURPOSE: To estimate annual health care and productivity loss costs attributable
      to overweight or obesity in working asthmatic patients. MATERIALS AND METHODS:
      This study was conducted using the 2003-2013 Medical Expenditure Panel Survey
      (MEPS) in the United States. Patients aged 18 to 64 years with asthma were
      identified via self-reported diagnosis, a Clinical Classification Code of 128, or
      a ICD-9-CM code of 493.xx. All-cause health care costs were estimated using a
      generalized linear model with a log function and a gamma distribution.
      Productivity loss costs were estimated in relation to hourly wages and missed
      work days, and a two-part model was used to adjust for patients with zero costs.
      To estimate the costs attributable to overweight or obesity in asthma patients,
      costs were estimated by the recycled prediction method. RESULTS: Among 11670
      working patients with a diagnosis of asthma, 4428 (35.2%) were obese and 3761
      (33.0%) were overweight. The health care costs attributable to obesity and
      overweight in working asthma patients were estimated to be $878 [95% confidence
      interval (CI): $861-$895] and $257 (95% CI: $251-$262) per person per year,
      respectively, from 2003 to 2013. The productivity loss costs attributable to
      obesity and overweight among working asthma patients were $256 (95% CI: $253
      $260) and $26 (95% CI: $26-$27) per person per year, respectively. CONCLUSION:
      Health care and productivity loss costs attributable to overweight and obesity in
      asthma patients are substantial. This study's results highlight the importance of
      effective public health and educational initiatives targeted at reducing
      overweight and obesity among patients with asthma, which may help lower the
      economic burden of asthma.

PMID- 27873515
TI  - Angiopoietin-1 Modified Human Umbilical Cord Mesenchymal Stem Cell Therapy for
      Endotoxin-Induced Acute Lung Injury in Rats.
AB  - PURPOSE: Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization
      and endothelial survival via inhibition of endothelial permeability and leukocyte
      endothelium interactions. Hence, we hypothesized that treatment with umbilical
      cord mesenchymal stem cells (UCMSCs) carrying the Ang1 gene (UCMSCs-Ang1) might
      be a potential approach for acute lung injury (ALI) induced by lipopolysaccharide
      (LPS). MATERIALS AND METHODS: UCMSCs with or without transfection with the human
      Ang1 gene were delivered intravenously into rats one hour after intra-abdominal
      instillation of LPS to induce ALI. After the rats were sacrificed at 6 hours, 24
      hours, 48 hours, 8 days, and 15 days post-injection of LPS, the serum, the lung
      tissues, and bronchoalveolar lavage fluid (BALF) were harvested for analysis,
      respectively. RESULTS: Administration of fluorescence microscope confirmed the
      increased presence of UCMSCs in the injured lungs. The evaluation of UCMSCs and
      UCMSCs-Ang1 actions revealed that Ang1 overexpression further decreased the
      levels of the pro-inflammatory cytokines TNF-alpha, TGF-beta1, and IL-6 and
      increased the expression of the anti-inflammatory cytokine IL-10 in the injured
      lungs. This synergy caused a substantial decrease in lung airspace inflammation
      and vascular leakage, characterized by significant reductions in wet/dry ratio,
      differential neutrophil counts, myeloperoxidase activity, and BALF. The rats
      treated by UCMSCs-Ang1 showed improved survival and lower ALI scores. CONCLUSION:
      UCMSCs-Ang1 could improve both systemic inflammation and alveolar permeability in
      ALI. UC-derived MSCs-based Ang1 gene therapy may be developed as a potential
      novel strategy for the treatment of ALI.

PMID- 27873516
TI  - Cyclosporine Sparing Effect of Enteric-Coated Mycophenolate Sodium in De Novo
      Kidney Transplantation.
AB  - PURPOSE: The increased tolerability of enteric-coated mycophenolate sodium (EC
      MPS), compared to mycophenolate mofetil, among kidney transplant recipients has
      the potential to facilitate cyclosporine (CsA) minimization. Therefore, a
      prospective trial to determine the optimum EC-MPS dose in CsA-based
      immunosuppression regimens is necessary. MATERIALS AND METHODS: A comparative,
      parallel, randomized, open-label study was performed for 140 patients from four
      centers to compare the efficacy and tolerability of low dose CsA with standard
      dose EC-MPS (the investigational group) versus standard dose CsA with low dose EC
      MPS (the control group) for six months in de novo kidney transplant recipients.
      Graft function, the incidence of efficacy failure [biopsy-confirmed acute
      rejection (BCAR), death, graft loss, loss to follow-up], and adverse events were
      compared. RESULTS: The mean estimated glomerular filtration rate (eGFR) of the
      investigational group at six months post-transplantation was non-inferior to that
      of the control group (confidence interval between 57.3 mL/min/1.73m2 and 67.4
      mL/min/1.73 m2, p<0.001). One graft loss was reported in the control group, and
      no patient deaths were reported in either group. The incidence of BCAR of the
      investigational group was 8.7%, compared to 18.8% in the control group (p=0.137),
      during the study period. There were no significant differences (p>0.05) in the
      incidence of discontinuations and serious adverse events (SAE) between the
      groups. CONCLUSION: CsA minimization using a standard dose of EC-MPS kept the
      incidence of acute rejection and additional risks as low as conventional
      immunosuppression and provided therapeutic equivalence in terms of renal graft
      function and safety issues.

PMID- 27873517
TI  - Reliability and Validity of the Korean Version of the Lifetime Stressor Checklist
      Revised in Psychiatric Outpatients with Anxiety or Depressive Disorders.
AB  - PURPOSE: Traumatic events and adverse stressful experiences are major etiological
      factors in a wide variety of physical and mental disorders. Developing
      psychological instruments that can be easily administered and that have good
      psychometric properties have become an integral part for research and practice.
      This study investigated the reliability and validity of the Korean version of the
      Lifetime Stressor Checklist-Revised (LSC-R) in a consecutive sample of
      psychiatric outpatients. The LSC-R is a 30-item self-reporting questionnaire
      examining lifetime traumatic and non-traumatic stressors. MATERIALS AND METHODS:
      A final sample of 258 outpatients with anxiety or depressive disorders was
      recruited at the psychiatric department of a university-affiliated teaching
      hospital. Self-reported data included the Life Events Checklist (LEC), the Zung
      Self-Rating Depression and Anxiety Scales, and the Impact of Events Scale
      Revised, in addition to the LSC-R. A convenience sample of 50 college students
      completed the LSC-R on two occasions separated by a three week-interval for test
      retest reliability. RESULTS: Mean kappa for temporal stability was high
      (kappa=0.651) and Cronbach alpha was moderate (alpha=0.724). Convergent validity
      was excellent with corresponding items on the LEC. Concurrent validity was good
      for symptoms of post-traumatic stress disorder, depression, and anxiety. An
      exploratory factor analysis revealed that 11 factors explained 64.3 % of the
      total variance. CONCLUSION: This study demonstrated good psychometric properties
      of the Korean version of the LSC-R, further supporting its use in clinical
      research and practice with a Korean speaking population.

PMID- 27873518
TI  - miR-379 Inhibits Cell Proliferation, Invasion, and Migration of Vascular Smooth
      Muscle Cells by Targeting Insulin-Like Factor-1.
AB  - PURPOSE: MicroRNAs are small non-coding RNAs that play important roles in
      vascular smooth muscle cell (VSMC) function. This study investigated the role of
      miR-379 on proliferation, invasion, and migration of VSMCs and explored
      underlying mechanisms thereof. MATERIALS AND METHODS: MicroRNA, mRNA, and protein
      levels were determined by quantitative real-time PCR and western blot. The
      proliferative, invasive, and migratory abilities of VSMCs were measured by CCK-8,
      invasion, and wound healing assay, respectively. Luciferase reporter assay was
      used to confirm the target of miR-379. RESULTS: Platelet-derived growth factor-bb
      was found to promote cell proliferation and suppress miR-379 expression in VSMCs.
      Functional assays demonstrated that miR-379 inhibited cell proliferation, cell
      invasion, and migration. Flow cytometry results further showed that miR-379
      induced apoptosis in VSMCs. TargetScan analysis and luciferase report assay
      confirmed that insulin-like growth factor-1 (IGF-1) 3'UTR is a direct target of
      miR-379, and mRNA and protein levels of miR-379 and IGF-1 were inversely
      correlated. Rescue experiments showed that enforced expression of IGF-1
      sufficiently overcomes the inhibitory effect of miR-379 on cell proliferation,
      invasion, and migration in VSMCs. CONCLUSION: Our results suggest that miR-379
      plays an important role in regulating VSMCs proliferation, invasion, and
      migration by targeting IGF-1.

PMID- 27873519
TI  - Use of Three-Dimensional Curved-Multiplanar Reconstruction Images for Sylvian
      Dissection in Microsurgery of Middle Cerebral Artery Aneurysms.
AB  - PURPOSE: The purpose of this study was to introduce a method of using three
      dimensional (3D) curved-multiplanar reconstruction (MPR) images for sylvian
      dissection during microsurgical treatment of middle cerebral artery (MCA)
      aneurysms. MATERIALS AND METHODS: Forty-nine patients who had undergone surgery
      for MCA aneurysms were enrolled. We obtained the 3D curved-MPR images along the
      sphenoid ridge using OsiriX MDTM imaging software, compared sylvian dissection
      time according to several 3D MPR image factors, and investigated the correlations
      between these images and intraoperative findings. RESULTS: Utilizing preoperative
      information of the sylvian fissure (SF) and peri-aneurysmal space on 3D curved
      MPR images, we could predict the feasibility of sylvian dissection for a safe
      surgery. 3D curved-MPR images showed several features: first, perpendicular
      images to the sylvian surface in the same orientation as the surgeon's view;
      second, simultaneous visualization of the brain cortex, vessels, and cisternal
      space; and third, more accurate measurement of various parameters, such as depth
      of the MCA from the sylvian surface and the location and width of the SFs.
      CONCLUSION: In addition to conventional image studies, 3D curved-MPR images seem
      to provide useful information for Sylvian dissection in the microsurgical
      treatment of MCA aneurysms.

PMID- 27873520
TI  - Rupture of Right Ventricular Free Wall Following Ventricular Septal Rupture in
      Takotsubo Cardiomyopathy with Right Ventricular Involvement.
AB  - Most patients diagnosed with takotsubo cardiomyopathies are expected to almost
      completely recover, and their prognosis is excellent. However, complications can
      occur in the acute phase. We present a case of a woman with takotsubo
      cardiomyopathy with right ventricular involvement who developed a rupture of the
      right ventricular free wall following ventricular septal rupture, as a
      consequence of an acute increase in right ventricular afterload by left-to-right
      shunt. Our case report illustrates that takotsubo cardiomyopathy can be life
      threatening in the acute phase. Ventricular septal rupture in biventricular
      takotsubo cardiomyopathy may be a harbinger of cardiac tamponade by right
      ventricular rupture.

PMID- 27873521
TI  - A Case of Recurrent Urticaria Due to Formaldehyde Release from Root-Canal
      Disinfectant.
AB  - Although formaldehyde is well known to cause type 4 hypersensitivity,
      immunoglobulin E (IgE)-mediated hypersensitivity to formaldehyde is rare. Here,
      we report a case of recurrent generalized urticaria after endodontic treatment
      using a para-formaldehyde (PFA)-containing root canal sealant and present a
      review of previous studies describing cases of immediate hypersensitivity
      reactions to formaldehyde. A 50-year-old man visited our allergy clinic for
      recurrent generalized urticaria several hours after endodontic treatment. Prick
      tests to latex, lidocaine, and formaldehyde showed negative reactions. However,
      swelling and redness at the prick site continued for several days. The level of
      formaldehyde-specific IgE was high (class 4). Thus, the patient was deemed to
      have experienced an IgE-mediated hypersensitivity reaction caused by the PFA used
      in the root canal disinfectant. Accordingly, we suggest that physicians should
      pay attention to type I hypersensitivity reactions to root canal disinfectants,
      even if the symptoms occur several hours after exposure.

PMID- 27873522
TI  - Extremely Well-Differentiated Papillary Thyroid Carcinoma Resembling Adenomatous
      Hyperplasia Can Metastasize to the Skull: A Case Report.
AB  - We describe herein histologic, immunohistochemical, and molecular findings and
      clinical manifestations of a rare case of an extremely well differentiated
      papillary thyroid carcinoma (EWD-PTC). Similarly, it is also difficult to
      diagnose follicular variant papillary thyroid carcinoma (FVPTC), whose diagnosis
      is still met with controversy. A recently reported entity of well-differentiated
      tumor of uncertain malignant potential (WDT-UMP) is added to the diagnostic
      spectrum harboring EWD-PTC and FVPTC. We report this case, because EWD-PTC is
      different from FVPTC in its papillary architecture, and also from WDT-UMP in its
      recurrence and metastatic pattern. These morphologically deceptive entities
      harbored diagnostic difficulties in the past because the diagnosis depended
      solely on histology. However, they are now diagnosed with more certainty by
      virtue of immunohistochemical and molecular studies. We experienced a case of EWD
      PTC, which had been diagnosed as adenomatous hyperplasia 20 years ago and
      manifested recurrence with lymph node (LN) metastasis 7 years later. After
      another 7 years of follow-up, a new thyroid lesion had developed, diagnosed as
      FVPTC, with LN metastasis of EWD-PTC. One year later, the patient developed
      metastatic FVPTC in the skull. Immunohistochemically, the EWD-PTC was focally
      positive for CK19, negative for galectin-3, and focally negative for CD56.
      Molecular studies revealed BRAF-positivity and K-RAS negativity. The FVPTC in the
      left thyroid showed both BRAF and K-RAS negativity. In conclusion, EWD-PTC and
      FVPTC share similar histologic features, but they are different tumors with
      different molecular biologic and clinical manifestations. A large cohort of EWD
      PTC should be included in further study.

PMID- 27873524
TI  - Erratum to "Clinical Experience with the Bentall Procedure: 28 Years" by Joo HC,
      et al. (Yonsei Med J 2012;53:915-23.).
AB  - This corrects the article on p. 915 in vol. 53, PMID: 22869473.

PMID- 27873523
TI  - Is Human Brucellosis Endemics in Korea?

PMID- 27873525
TI  - ?

PMID- 27873526
TI  - EVALUATION OF COMPLICATIONS AFTER ENDOSCOPY ASSISTED OPEN REDUCTION AND INTERNAL
      FIXATION OF UNILATERAL CONDYLAR FRACTURES OF THE MANDIBLE. RETROSPECTIVE ANALYSIS
      2010-2015.
AB  - BACKGROUND: The authors present their experience with endoscopy assisted open
      reduction and internal fixation of condylar fractures of the mandible. Their
      results are presented in a retrospective study of 33 patients with unilateral
      subcondylar fracture, who underwent a surgical procedure between 2010 and 2015.
      Reduction and fixation, stability of occlusion 12 months after the operation and
      also presence of complications were evaluated. RESULTS: Satisfactory reduction
      (anatomic or physiologic) was achieved in 31 patients. Stability of occlusion was
      worse in 1 patient (due to condylar absorption). Complications included mainly
      inflammatory complications (4 patients) and temporary paresis of the facial nerve
      (3 patients). Impaired function of temporomandibular joint was not reported in
      any of the patients. CONCLUSION: Endoscopy assisted open reduction and internal
      fixation is an alternative to classical surgical procedures, however it requires
      special instrumentarium and experienced surgical team.

PMID- 27873527
TI  - NUMERICAL EVALUATION OF SCAR AFTER BREAST RECONSTRUCTION WITH ABDOMINAL
      ADVANCEMENT FLAP.
AB  - BACKGROUND: The treatment of breast cancer has developed a lot during the last
      decade, nevertheless it still remains a considerable social and economical
      problem all over the world. The choice of the surgical procedure depends on a
      patients protocol and the surgeons preferences. The aim of this study is to
      evaluate the stress on the scar after breast reconstruction. METHODS:
      Mathematical modeling of the sutured skin flap used for breast implant placement
      was divided into the following two steps. At first, material model of the
      selected silicone implant was identified. Afterwards, the mathematical model of
      the breast and implant was performed. RESULTS: Maximal geometrical deviation for
      anatomical and round implant is placed on the lower surface of the breast and
      upper surface of the breast, while in the area of lateral geometry and the area
      around the nipple the agreement reaches very high level. The maximal tension is
      located in two median stitches. The maximal force reaches 0.025 N. The Cauchy
      stress equivalent is located around the nipple and reaches the value of 380 kPa.
      CONCLUSION: From our results it can be seen, that the anatomical and round breast
      implants do not result in the same stress on the scar. The maximal value
      difference reaches 13.4% between stress values for these two breast implants and
      the round implant results in higher loaded scar compared to the anatomical
      implant.

PMID- 27873528
TI  - TRANSPLANTATION OF VASCULARIZED COMPOSITE ALLOGRAFTS. REVIEW OF CURRENT
      KNOWLEDGE.
AB  - Transplantation in reconstructive surgery has been performed for more than 20
      years, although the official beginning of these procedures is considered the
      first successful transplantation of the hand in 1998. The original name
      "Composite Tissue Transplantation" has been used less frequently; more common is
      the term "Vascularized Composite Allotransplant", which better describes the
      basis of the procedure. There have been so far approximately 180 transplantations
      performed, the exact number is difficult to find. The most known transplantation
      from this group include transplantation of the hand and face, the other, such as
      transplantation of the abdominal wall, joints, bones, trachea, larynx, tongue,
      penis, uterus, etc. are less common and less well known. The common
      characteristics is that they are not used for salvage or prolongation of life,
      but to improve its quality. The quality of life is a value, which cannot be
      objectively measured and the opinions regarding its importance significantly
      differ. Therefore there is still an unsolved ethical issue regarding these
      procedures, which is based on the justification to use immunosuppressive therapy
      with its serious risks in cases when the procedure is not needed for salvage or
      preservation of life.

PMID- 27873529
TI  - TRACHEAL ALLOTRANSPLANTATION AND REGENERATION.
AB  - Non-malignant and malignant obstruction of the tracheal airway causes significant
      morbidity and mortality. With increased use of artificial airways, benign and
      iatrogenic complications are increasing. A tracheal stenosis that is less than 5
      cm in length can be resected with end-to-end anastomosis. Longer tracheal lesions
      can be treated in a palliative way by placement of a stent to secure airway lumen
      patency. The management of tracheal defects is an evolving field. Tracheal
      transplantation and tracheal regeneration may provide major treatment advances to
      cases with long-segment tracheal involvement. This review examines the current
      possibilities and future prospects in the area of tracheal transplantation and
      regeneration.

PMID- 27873530
TI  - PULMONARY EMBOLISM AFTER ABDOMINOPLASTY - ARE WE REALLY ABLE TO AVOID ALL
      COMPLICATIONS? CASE REPORTS AND LITERATURE REVIEW.
AB  - Pulmonary embolism is a potentially lethal complication in plastic surgery
      patients. About 34% of the members of American Society of Plastic Surgery have
      diagnosed pulmonary embolism in their patients, and 7% had experienced at least 1
      death due to this complication. The American Society of Plastic Surgeons
      Executive Committee approved the Venous Thromboembolism Task Force Report. The
      members agreed that there was not enough evidence to make all-inclusive
      recommendations for plastic surgery deep vein thrombosis and pulmonary embolism
      prophylaxis, but released the 2005 Caprini Scale accompanied by the Task Force
      recommendations for use in plastic surgery. It is generally strongly advised to
      use appropriate prophylactic measures against venous thromboembolism in all
      surgical procedures. However, even then we cannot completely avoid this serious
      complication.

PMID- 27873532
TI  - IS NON-TRAUMATIC NAIL DYSTRPOPHY ONLY DUE TO CHRONIC ONYCHOMYCOSIS? THE
      ONYCHOMATRICOMA. CASE REPORT.
AB  - Onychomatricoma is a rare benign fibroepithelial tumour that originates from the
      nail matrix and can affect the nail bed of fingers and toes. Onychomatricoma may
      represent a premalignant lesion and although the etiology is still not fully
      understood, a previous finger trauma is considered the main predisposing factor.
      Unlike previous scientific articles we report a case of a "non traumatic"
      onychomatricoma in a 60 years old woman underlining the clinical and histological
      features to distinguish this uncommon lesion from other lesions originating from
      the nail apparatus.

PMID- 27873531
TI  - USE OF OSTEOTOMY IN POST-TRAUMATIC DEFORMITY OF FRONTAL SINUS ANTERIOR WALL. CASE
      REPORT.
AB  - Post-traumatic deformity of frontal sinus anterior table can be treated in
      various ways. Usage of a certain type of an implant is a common method. We
      performed an osteotomy and subsequent reduction of the fragments to reconstruct
      their anatomical position. Titanium miniplates and screws were used for fixation.
      This case report suggests a possible use of this method in patients with more
      extensive frontal sinus and distinct post-traumatic deformity. No similar case
      manages as described in our case report was found in the literature.

PMID- 27873533
TI  - SALUTATIO ET LAUDATIO AD ANNIVERSARIUM PROFESSORIS WILLIAM GUNN.

PMID- 27873534
TI  - Corrigendum.

PMID- 27873535
TI  - Loading of the lumbar spine during backpack carriage.
AB  - Backpack carriage is significantly associated with a higher prevalence of low
      back pain. Elevated compression and shear forces in the lumbar intervertebral
      discs are known risk factors. A novel method of calculating the loads in the
      lumbar spine during backpack carriage is presented by combining physical and
      numerical modelling. The results revealed that to predict realistic lumbar
      compression forces, subject-specific lumbar curvature data were not necessary for
      loads up to 40 kg. In contrast, regarding shear forces, using subject-specific
      lumbar curvature data from upright MRI measurements as input for the rigid body
      model significantly altered lumbar joint force estimates.

PMID- 27873536
TI  - Discomfort and avoidance of touch: new insights on the emotional deficits of
      social anxiety.
AB  - Physical touch is central to the emotional intimacy that separates romantic
      relationships from other social contexts. In this study of 256 adults (128
      heterosexual couples, mean relationship length = 20.5 months), we examined
      whether individual differences in social anxiety influenced comfort with and
      avoidance of physical touch. Because of prior work on sex difference in touch
      use, touch comfort, and social anxiety symptoms and impairment, we explored sex
      specific findings. We found evidence that women with greater social anxiety were
      less comfortable with touch and more avoidant of touch in same-sex friendships.
      Additionally, a woman's social anxiety had a bigger effect on a man's comfort
      with touch and avoidance of touch in the romantic relationship than a man's
      social anxiety had on the woman's endorsement of touch-related problems. These
      effects were uninfluenced by the length of romantic relationships. Touch is a
      neglected emotional experience that offers new insights into the difficulties of
      individuals suffering from social anxiety problems, and their romantic partners.

PMID- 27873537
TI  - Brain region-specific effects of immobilization stress on cholinesterases in
      mice.
AB  - Brain acetylcholinesterase (AChE) variant AChER expression increases with acute
      stress, and this persists for an extended period, although the timing, strain and
      laterality differences, have not been explored previously. Acute stress
      transiently increases acetylcholine release, which in turn may increase activity
      of cholinesterases. Also the AChE gene contains a glucocorticoid response element
      (GRE), and stress-inducible AChE transcription and activity changes are linked to
      increased glucocorticoid levels. Corticotropin-releasing hormone knockout (CRH
      KO) mice have basal glucocorticoid levels similar to wild type (WT) mice, but
      much lower levels during stress. Hence we hypothesized that CRH is important for
      the cholinesterase stress responses, including butyrylcholinesterase (BChE). We
      used immobilization stress, acute (30 or 120 min) and repeated (120 min daily *
      7) in 48 male mice (24 WT and 24 CRH-KO) and determined AChER, AChE and BChE mRNA
      expression and AChE and BChE activities in left and right brain areas (as
      cholinergic signaling shows laterality). Immobilization decreased BChE mRNA
      expression (right amygdala, to 0.5, 0.3 and 0.4, * control respectively) and
      AChER mRNA expression (to 0.5, 0.4 and 0.4, * control respectively). AChE mRNA
      expression increased (1.3, 1.4 and 1.8-fold, respectively) in the left striatum
      (Str). The AChE activity increased in left Str (after 30 min, 1.2-fold),
      decreased in right parietal cortex with repeated stress (to 0.5 * control). BChE
      activity decreased after 30 min in the right CA3 region (to 0.4 * control) but
      increased (3.8-fold) after 120 min in the left CA3 region. The pattern of changes
      in CRH-KO differed from that in WT mice.

PMID- 27873538
TI  - The effects of elevated hearing thresholds on performance in a paintball
      simulation of individual dismounted combat.
AB  - OBJECTIVE: To examine the relationship between hearing acuity and operational
      performance in simulated dismounted combat. DESIGN: Individuals wearing hearing
      loss simulation systems competed in a paintball-based exercise where the
      objective was to be the last player remaining. Four hearing loss profiles were
      tested in each round (no hearing loss, mild, moderate and severe) and four rounds
      were played to make up a match. This allowed counterbalancing of simulated
      hearing loss across participants. STUDY SAMPLE: Forty-three participants across
      two data collection sites (Fort Detrick, Maryland and the United States Military
      Academy, New York). All participants self-reported normal hearing except for two
      who reported mild hearing loss. RESULTS: Impaired hearing had a greater impact on
      the offensive capabilities of participants than it did on their "survival",
      likely due to the tendency for individuals with simulated impairment to adopt a
      more conservative behavioural strategy than those with normal hearing.
      CONCLUSIONS: These preliminary results provide valuable insights into the impact
      of impaired hearing on combat effectiveness, with implications for the
      development of improved auditory fitness-for-duty standards, the establishment of
      performance requirements for hearing protection technologies, and the refinement
      of strategies to train military personnel on how to use hearing protection in
      combat environments.

PMID- 27873539
TI  - Can an external device create and trigger intention in a patient with a severe
      brain injury?
AB  - Goal-directed behaviour (GDB), the capacity that allows us to control our
      environment according to our desires and needs, requires different stages from
      initial intention to goal achievement. Although GDB is frequently disrupted after
      acquired brain injury, few studies have addressed the remediation of reduced GDB
      in patients with severe brain injury. The present study aimed to raise this
      question in RZ, a patient with severe brain injury who presented a serious
      reduction in GDB related to difficulties in creating an intention from internal
      determinants and in selecting an action plan, as well as to memory and
      attentional impairments. Our objective was to investigate the efficacy of an
      intervention programme to create and trigger a specific intention in RZ. More
      specifically, this programme consisted in written prompts, first accompanied by
      an alarm provided by his mobile phone, but gradually reduced until only the alarm
      remained, which was implemented in order to improve RZ's attendance at workshop
      sessions. Results showed that RZ's attendance rate at the workshop sessions
      increased, indicating that the use of an external device allowed us to create and
      trigger intention in a patient with severe cognitive impairments.

PMID- 27873540
TI  - [Stress related correlates of anxiety and depression in girls with chronic
      headache].
AB  - Chronic headache in adolescents is frequent and often associated with anxiety and
      depression. The present study investigated, whether psychological and physical
      stress symptoms have an infl uence on the occurrence of anxiety and depression
      and what is the role of stress coping. The sample consisted of 77 15 years old
      girls with chronic headache and 72 girls, who served as controls. Stress symptoms
      and stress coping were measured with the Stressverarbeitungsfragebogen fur Kinder
      und Jugendliche (Coping with Stress Questionnaire for Children and Adolescents),
      depression was assessed by the Depression Inventory for Children and Adolescents,
      anxiety by the State-Trait Anxiety Inventory for Children. Linear regression was
      used to analyze the relationship between stress factors and anxiety resp.
      depression. Physical stress symptoms were related to anxiety, but not to
      depression. Coping strategies of the depressed as well as the anxious children
      were characterized by stress reinforcing behaviors. The results point to focusing
      on physical symptoms in the anxious headache patients and to avoidance coping in
      the depressed children.

PMID- 27873541
TI  - The relationship between suppression and subsequent intrusions: the mediating
      role of peritraumatic dissociation and anxiety.
AB  - BACKGROUND AND OBJECTIVES: Although previous studies showed that thought and
      emotion suppression represent risk factors for intrusions development, the
      mechanisms that explain these relations were less explored. This study aims to
      examine the relationships between thought and emotion suppression and the
      symptoms of intrusion following the exposure to a trauma-related event. Moreover,
      we explored if these relationships would be mediated by peritraumatic state
      dissociation and state anxiety. DESIGN AND METHODS: The trauma film paradigm was
      used and the participants were students (N = 148) experimentally exposed to an
      aversive film to model a traumatic experience. Thought and emotion suppression
      were measured before the trauma exposure. After exposure, the participants
      completed scales for measuring state dissociation and state anxiety. Intrusive
      images and thoughts of the film were recorded in the subsequent week using an
      intrusion diary. RESULTS: Thought suppression predicted intrusive thoughts
      frequency, and this effect was mediated by the peritraumatic anxiety. State
      anxiety predicted both intrusive images and thoughts, while state dissociation
      only predicted intrusive images. CONCLUSIONS: Intrusive images and intrusive
      thoughts are different phenomena and they are predicted by different variables.
      The practical implications of these results for posttraumatic stress disorder
      treatment and secondary traumatization are discussed.

PMID- 27873542
TI  - A 6-year surveillance study of "Stingers" in NCAA American Football.
AB  - This study describes the epidemiology of "stinger" injuries in National
      Collegiate Athletic Association (NCAA) Men's Football. About 57 NCAA Men's
      Football programmes provided 153 team-seasons of injury data to the NCAA Injury
      Surveillance Programme (NCAA-ISP) during the 2009/2010-2014/2015 academic years.
      In the study period, 229 "stingers" were reported for an injury rate of
      2.04/10,000 athlete-exposures (AE). Most "stingers" were reported during
      competitions (55.5%) and the preseason (80.3%) and resulted in time loss less
      than 24 hours (63.8%). One in five (18.8%) were recurrent. Most "stingers" were
      due to player contact (93.0%), particularly while tackling (36.7%) and blocking
      (25.8%) and occurred to defensive ends/linebackers (25.8%) and offensive linemen
      (23.6%). Although previous research reports a large prevalence of "stingers"
      among football players, the NCAA-ISP reported a relatively low injury rate. The
      transient nature of pain associated with "stingers" may have contributed to under
      reporting, highlighting the need to deduce manners to increase reporting.

PMID- 27873543
TI  - Hearing aid fitting and fine-tuning based on estimated individual traits.
AB  - OBJECTIVE: A generalised concept for hearing aid fitting and fine-tuning based on
      estimated individual traits is presented along first implementations in this
      report. DESIGN: To estimate the individual traits, a set of auditory model-based
      performance measures is used to generate promising candidates within the
      algorithm's parameter space for a subsequent subjective rating. For the
      subjective assessment, a fast and intuitive multi-stimulus test denoted as
      combined discrimination and classification (CoDiCl) is presented to capture user
      preferences for an optimised setting. STUDY SAMPLE: The estimation of individual
      traits is shown in an exemplary manner for a multidimensional coherence-based
      noise reduction algorithm. The dimensionality reduction was performed using
      differently weighted combinations of speech intelligibility index (SII) and
      perceived similarity measure (PSM). RESULTS: Nine reasonable alternative
      algorithm setting candidates were extracted from a model-optimised exploration
      path (MOEP) for a subsequent subjective rating to potentially differentiate
      between listeners with different attitudes towards noise suppression and
      introduced distortions (i.e. "noise haters" and "distortion haters").
      CONCLUSIONS: By iteratively improving the agreement between subjective and
      objective assessment, an objective estimation of subjective traits using
      appropriate weightings of objective measures may become possible. This will
      potentially help to efficiently fit modern multidimensional hearing aid
      algorithms to the individual user.

PMID- 27873544
TI  - Erratum.

PMID- 27873545
TI  - Presence of Lactobacillus reuteri in saliva coincide with higher salivary IgA in
      young adults after intake of probiotic lozenges.
AB  - The aim of this study was to compare the concentration of salivary immunoglobulin
      A (IgA) and the selected interleukins (IL)-1beta, IL-6, IL-8 and IL-10 in young
      individuals with presence and non-presence of Lactobacillus reuteri in saliva
      after a three-week intervention with probiotic lozenges. The study group
      consisted of 47 healthy individuals aged 18-32 years with no clinical signs of
      oral inflammation. In a randomised, double-blind, placebo-controlled, cross-over
      trial participants ingested two lozenges per day containing two strains of the
      probiotic bacterium L. reuteri or placebo lozenges. The intervention and wash-out
      periods were three weeks. Stimulated and unstimulated whole saliva was collected
      at baseline and immediately after termination of the intervention periods. The
      samples were analysed for total protein, salivary IgA and selected cytokines. In
      this extended analysis, data were collected by analysing baseline and follow-up
      saliva samples related to ingestion of the probiotic lozenges for the presence of
      L. reuteri through DNA-extraction, PCR-amplification and gel-electrophoresis. At
      baseline, 27% of the individuals displayed presence of L. reuteri and 42% were
      positive immediately after the three-week probiotic intervention. Individuals
      with presence of L. reuteri in saliva had significantly higher (P<0.05)
      concentrations of salivary IgA and %IgA/protein at the termination of the
      probiotic intake compared with non-presence. No differences in the cytokine
      levels were observed. In conclusion, detectable levels of L. reuteri in saliva
      coincided with higher concentrations of salivary IgA and %IgA/protein in
      stimulated whole saliva after the three-week daily intake of probiotic lozenges.
      Our findings suggest that monitoring the presence of probiotic candidates in the
      oral environment is important to interpret and understand their possible immune
      modulating role in maintaining oral health.

PMID- 27873546
TI  - Evaluation of the effect of soymilk fermented by a riboflavin-producing
      Lactobacillus plantarum strain in a murine model of colitis.
AB  - Inflammatory bowel diseases (IBD) are idiopathic diseases of the gastrointestinal
      tract characterised by recurrent inflammation that require lifelong treatments.
      It has been shown that certain strains of lactic acid bacteria (LAB) can produce
      specific health-promoting compounds in foods or in the gastrointestinal tract
      that can in turn prevent and/or treat IBD. This study was designed to evaluate
      the possible therapeutic potential of soymilk fermented by the riboflavin
      producing strain Lactobacillus plantarum CRL 2130 in a trinitrobenzene sulfonic
      induced colitis mouse model. Mice that received soymilk fermented by L. plantarum
      CRL 2130 showed a decrease in weight loss, lower damage scores in their large
      intestines, lower microbial translocation to liver and decreased cytokines levels
      in their intestinal fluids compared to animals that received unfermented soymilk
      or soymilk fermented by a non-riboflavin-producing L. plantarum strain. This is
      the first report that demonstrates that a riboflavin-producing LAB was able to
      prevent experimental colitis in a murine model.

PMID- 27873547
TI  - Daily ingestion of the probiotic Lactobacillus paracasei ST11 decreases Vaccinia
      virus dissemination and lethality in a mouse model.
AB  - Vaccinia virus (VACV) is an important pathogen. Although studies have shown
      relationships between probiotics and viruses, the effect of probiotics on VACV
      infection is unknown. Therefore, this work aims to investigate the probiotics
      effects on VACV infection. Mice were divided into four groups, two non-infected
      groups, one receiving the probiotic, the other one not receiving it, and two
      groups infected intranasally with VACV Western Reserve (VACV-WR) receiving or not
      receiving the probiotic. Viral titres in organs and cytokine production in the
      lungs were analysed. Lung samples were also subjected to histological analysis.
      The intake of probiotic results in reduction in viral spread with a significant
      decrease of VACV titer on lung, liver and brain of treated group. In
      addition,treatment with the probiotic results in attenuated mice lung
      inflammation showing fewer lesions on histological findings and decreased
      lethality in mice infected with VACV. The ingestion of Lactobacillus paracasei
      ST11 (LPST11) after VACV infection resulted in 2/9 animal lethality compared with
      4/9 in the VACV group. This is the first study on probiotics and VACV
      interactions, providing not only information about this interaction, but also
      proposing a model for future studies involving probiotics and other poxvirus.

PMID- 27873548
TI  - A reliability generalization meta-analysis of coefficient alpha and test-retest
      coefficient for the aging males' symptoms (AMS) scale.
AB  - PURPOSE: The aging males' symptoms (AMS) scale is an instrument used to determine
      the health-related quality of life in adult and elderly men. The purpose of this
      study was to synthesize internal consistency (Cronbach's alpha) and test-retest
      reliability for the AMS scale and its three subscales. METHODS: Of the 123
      studies reviewed, 12 provided alpha coefficients which were then used in the meta
      analyses of internal consistency. Seven of the 12 included studies provided test
      retest coefficients, and these were used in the meta-analyses of test-retest
      reliability. RESULTS: The AMS scale had excellent internal consistency [alpha =
      0.89 (95% CI 0.88-0.90)]; the mean alpha estimates across the AMS subscales
      ranged from 0.79 to 0.82. The AMS scale also had good test-retest reliability [r
      = 0.85 (95% CI 0.82-0.88]; the test-retest reliability coefficients of the AMS
      subscales ranged from 0.76 to 0.83. There was significant heterogeneity among the
      included studies. CONCLUSIONS: The AMS scale and the three subscales had fairly
      good internal consistency and test-retest reliability. Future psychometric
      studies of the AMS scale should report important characteristics of the
      participants, details of item scores, and test-retest reliability.

PMID- 27873549
TI  - A systematic review of recommended modifications of CBT for people with cognitive
      impairments following brain injury.
AB  - Due to diverse cognitive, emotional and interpersonal changes that can follow
      brain injury, psychological therapies often need to be adapted to suit the
      complex needs of this population. The aims of the study were to synthesise
      published recommendations for therapy modifications following brain injury from
      non-progressive traumatic, vascular, or metabolic causes and to determine how
      often such modifications have been applied to cognitive behavioural therapy (CBT)
      for post-injury emotional adjustment problems. A systematic review and narrative
      synthesis of therapy modifications recommended in review articles and reported in
      intervention studies was undertaken. Database and manual searches identified 688
      unique papers of which eight review articles and 16 intervention studies met
      inclusion criteria. The review articles were thematically analysed and a
      checklist of commonly recommended modifications composed. The checklist items
      clustered under themes of: therapeutic education and formulation; attention;
      communication; memory; and executive functioning. When this checklist was applied
      to the intervention studies, memory aids and an emphasis on socialising patients
      to the CBT model were most frequently reported as adaptations. It was concluded
      that the inconsistent reporting of psychological therapy adaptations for people
      with brain injury is a barrier to developing effective and replicable therapies.
      We present a comprehensive account of potential modifications that should be used
      to guide future research and practice.

PMID- 27873550
TI  - Self and other body perception in anorexia nervosa: The role of posterior DMN
      nodes.
AB  - OBJECTIVES: Body image distortion is a core symptom of anorexia nervosa (AN),
      which involves alterations in self- (and other's) evaluative processes arising
      during body perception. At a neural level, self-related information is thought to
      rely on areas of the so-called default mode network (DMN), which, additionally,
      shows prominent synchronised activity at rest. METHODS: Twenty female patients
      with AN and 20 matched healthy controls were scanned using magnetic resonance
      imaging when: (a) viewing video clips of their own body and another's body; (b)
      at rest. Between-group differences within the DMN during task performance were
      evaluated and further explored for task-related and resting-state-related
      functional connectivity alterations. RESULTS: AN patients showed a
      hyperactivation of the dorsal posterior cingulate cortex during their own-body
      processing but a response failure to another's body processing at the precuneus
      and ventral PCC. Increased task-related connectivity was found between dPCC
      dorsal anterior cingulate cortex and precuneus-mid-temporal cortex. Further, AN
      patients showed decreased resting-state connectivity between the dPCC and the
      angular gyrus. CONCLUSIONS: The PCC and the precuneus are suggested as key
      components of a network supporting self-other-evaluative processes implicated in
      body distortion, while the existence of DMN alterations at rest might reflect a
      sustained, task-independent breakdown within this network in AN.

PMID- 27873551
TI  - On the Methodological Implications of Extracting Muscle Synergies from Human
      Locomotion.
AB  - We investigated the influence of three different high-pass (HP) and low-pass (LP)
      filtering conditions and a Gaussian (GNMF) and inverse-Gaussian (IGNMF) non
      negative matrix factorization algorithm on the extraction of muscle synergies
      from myoelectric signals during human walking and running. To evaluate the
      effects of signal recording and processing on the outcomes, we analyzed the
      intraday and interday computation reliability. Results show that the IGNMF
      achieved a significantly higher reconstruction quality and on average needs one
      less synergy to sufficiently reconstruct the original signals compared to the
      GNMF. For both factorizations, the HP with a cut-off frequency of 250[Formula:
      see text]Hz significantly reduces the number of synergies. We identified the
      filter configuration of fourth order, HP 50[Formula: see text]Hz and LP
      20[Formula: see text]Hz as the most suitable to minimize the combination of
      fundamental synergies, providing a higher reliability across all filtering
      conditions even if HP 250[Formula: see text]Hz is excluded. Defining a
      fundamental synergy as a single-peaked activation pattern, for walking and
      running we identified five and six fundamental synergies, respectively using both
      algorithms. The variability in combined synergies produced by different filtering
      conditions and factorization methods on the same data set suggests caution when
      attributing a neurophysiological nature to the combined synergies.

PMID- 27873552
TI  - Correlated EEG Signals Simulation Based on Artificial Neural Networks.
AB  - In recent years, simulation of the human electroencephalogram (EEG) data found
      its important role in medical domain and neuropsychology. In this paper, a novel
      approach to simulation of two cross-correlated EEG signals is proposed. The
      proposed method is based on the principles of artificial neural networks (ANN).
      Contrary to the existing EEG data simulators, the ANN-based approach was
      leveraged solely on the experimentally acquired EEG data. More precisely,
      measured EEG data were utilized to optimize the simulator which consisted of two
      ANN models (each model responsible for generation of one EEG sequence). In order
      to acquire the EEG recordings, the measurement campaign was carried out on a
      healthy awake adult having no cognitive, physical or mental load. For the
      evaluation of the proposed approach, comprehensive quantitative and qualitative
      statistical analysis was performed considering probability distribution,
      correlation properties and spectral characteristics of generated EEG processes.
      The obtained results clearly indicated the satisfactory agreement with the
      measurement data.

PMID- 27873553
TI  - Real-Time Control of an Exoskeleton Hand Robot with Myoelectric Pattern
      Recognition.
AB  - Robot-assisted training provides an effective approach to neurological injury
      rehabilitation. To meet the challenge of hand rehabilitation after neurological
      injuries, this study presents an advanced myoelectric pattern recognition scheme
      for real-time intention-driven control of a hand exoskeleton. The developed
      scheme detects and recognizes user's intention of six different hand motions
      using four channels of surface electromyography (EMG) signals acquired from the
      forearm and hand muscles, and then drives the exoskeleton to assist the user
      accomplish the intended motion. The system was tested with eight neurologically
      intact subjects and two individuals with spinal cord injury (SCI). The overall
      control accuracy was [Formula: see text] for the neurologically intact subjects
      and [Formula: see text] for the SCI subjects. The total lag of the system was
      approximately 250[Formula: see text]ms including data acquisition, transmission
      and processing. One SCI subject also participated in training sessions in his
      second and third visits. Both the control accuracy and efficiency tended to
      improve. These results show great potential for applying the advanced myoelectric
      pattern recognition control of the wearable robotic hand system toward improving
      hand function after neurological injuries.

PMID- 27873555
TI  - Different Gene Therapy Strategies: A Overview for Prostate Cancer.
AB  - Gene therapy emerged as a mighty alternative for conventional treatment of
      multiple diseases. It has been defined as a product "that mediate their effects
      by transcription and/or translation of transferred genetic material and/or by
      integrating into the host genome and that are administered as nucleic acids,
      viruses, or genetically engineered microorganisms. The products may be used to
      modify cells in vivo or transferred to cells ex vivo prior to administration to
      the recipient". The first therapeutic gene therapy human trial was conducted in
      1990 by Michael R. Blaese, and besides its potential, the technique suffered a
      major drawback after the tragical death of Jesse Gelsinger, caused by his immune
      response against the viral vector used in his treatment. To date, gene therapy
      has regained some popularity and more than 2000 clinical trials are ongoing, most
      of them related to the treatment or prevention of various types of cancer.
      Nevertheless, some types of cancer contain a rare population of stem-like cells,
      capable of differentiation into tumor cells, promoting the re-incidence of
      tumors. Those cells are generally more resilient to chemotherapy and radiotherapy
      and are related to tumor initiation, progression, recurrence and metastasis. The
      human prostate cancer (PCa) is highly heterogeneous and multifactorial, and even
      the markers are not precise enough to predict the clinical outcome. Furthermore,
      even though currently therapies can efficiently remove the tumors, the re
      incidence rates are high. Gene therapy offers a handful of treatments that can
      halt oncogenes activation, promote the expression of suppressor genes or target
      cancer cells directly and induce apoptosis. Besides the risks involved, gene
      therapy can be of great help in the treatment of cancers and other diseases. This
      review aims to address the safety and potential of different gene therapy
      strategies used in the treatment of cancers.

PMID- 27873554
TI  - A Realistic Seizure Prediction Study Based on Multiclass SVM.
AB  - A patient-specific algorithm, for epileptic seizure prediction, based on
      multiclass support-vector machines (SVM) and using multi-channel high-dimensional
      feature sets, is presented. The feature sets, combined with multiclass
      classification and post-processing schemes aim at the generation of alarms and
      reduced influence of false positives. This study considers 216 patients from the
      European Epilepsy Database, and includes 185 patients with scalp EEG recordings
      and 31 with intracranial data. The strategy was tested over a total of
      16,729.80[Formula: see text]h of inter-ictal data, including 1206 seizures. We
      found an overall sensitivity of 38.47% and a false positive rate per hour of
      0.20. The performance of the method achieved statistical significance in 24
      patients (11% of the patients). Despite the encouraging results previously
      reported in specific datasets, the prospective demonstration on long-term EEG
      recording has been limited. Our study presents a prospective analysis of a large
      heterogeneous, multicentric dataset. The statistical framework based on
      conservative assumptions, reflects a realistic approach compared to constrained
      datasets, and/or in-sample evaluations. The improvement of these results, with
      the definition of an appropriate set of features able to improve the distinction
      between the pre-ictal and nonpre-ictal states, hence minimizing the effect of
      confounding variables, remains a key aspect.

PMID- 27873556
TI  - Between-individual variation in nematode burden among juveniles in a wild host.
AB  - Parasite infection in young animals can affect host traits related to demographic
      processes such as survival and reproduction, and is therefore crucial to
      population viability. However, variation in infection among juvenile hosts is
      poorly understood. Experimental studies have indicated that effects of parasitism
      can vary with host sex, hatching order and hatch date, yet it remains unclear
      whether this is linked to differences in parasite burdens. We quantified
      gastrointestinal nematode burdens of wild juvenile European shags (Phalacrocorax
      aristotelis) using two in situ measures (endoscopy of live birds and necropsy of
      birds that died naturally) and one non-invasive proxy measure (fecal egg counts
      (FECs)). In situ methods revealed that almost all chicks were infected (98%),
      that infections established at an early age and that older chicks hosted more
      worms, but FECs underestimated prevalence. We found no strong evidence that
      burdens differed with host sex, rank or hatch date. Heavier chicks had higher
      burdens, demonstrating that the relationship between burdens and their costs is
      not straightforward. In situ measures of infection are therefore a valuable tool
      in building our understanding of the role that parasites play in the dynamics of
      structured natural populations.

PMID- 27873557
TI  - Face processing in adolescents with positive and negative threat bias.
AB  - BACKGROUND: Individuals with anxiety disorders exhibit a 'vigilance-avoidance'
      pattern of attention to threatening stimuli when threatening and neutral stimuli
      are presented simultaneously, a phenomenon referred to as 'threat bias'.
      Modifying threat bias through cognitive retraining during adolescence reduces
      symptoms of anxiety, and so elucidating neural mechanisms of threat bias during
      adolescence is of high importance. We explored neural mechanisms by testing
      whether threat bias in adolescents is associated with generalized or threat
      specific differences in the neural processing of faces. METHOD: Subjects were
      categorized into those with (n = 25) and without (n = 27) threat avoidance based
      on a dot-probe task at average age 12.9 years. Threat avoidance in this cohort
      has previously been shown to index threat bias. Brain response to individually
      presented angry and neutral faces was assessed in a separate session using
      functional magnetic resonance imaging. RESULTS: Adolescents with threat avoidance
      exhibited lower activity for both angry and neutral faces relative to controls in
      several regions in the occipital, parietal, and temporal lobes involved in early
      visual and facial processing. Results generalized to happy, sad, and fearful
      faces. Adolescents with a prior history of depression and/or an anxiety disorder
      had lower activity for all faces in these same regions. A subset of results
      replicated in an independent dataset. CONCLUSIONS: Threat bias is associated with
      generalized, rather than threat-specific, differences in the neural processing of
      faces in adolescents. Findings may aid in the development of novel treatments for
      anxiety disorders that use attention training to modify threat bias.

PMID- 27873558
TI  - Antenatal depressive symptoms as a predictor of deterioration in perceived social
      support across the perinatal period: a four-wave cohort study in Turkey.
AB  - BACKGROUND: In a perinatal cohort of women in urban and rural Turkey, we
      investigated associations between antenatal depressive symptoms and subsequent
      changes in perceived quality of key family relationships. METHOD: Of 730 women
      recruited in their third trimester (94.6% participation), 578 (79.2%) were
      reassessed at a mean of 4.1 (s.d. = 3.3) months after childbirth, 488 (66.8%)
      were reassessed at 13.7 (s.d. = 2.9) months, and 448 (61.4%) at 20.8 (s.d. = 2.7)
      months. At all four examinations, self-reported quality of relationship with the
      husband, mother and mother-in-law was ascertained using the Close Persons
      Questionnaire with respect to emotional support, practical support and negative
      aspects of the relationship. Antenatal depressive symptoms were defined using the
      Edinburgh Postnatal Depression Scale. A range of covariates in mixed models was
      considered including age, education, number of children, family structure,
      physical health, past emotional problems and stressful life events. RESULTS: Key
      findings were as follows: (i) reported emotional and practical support from all
      three relationships declined over time in the cohort overall; (ii) reported
      emotional support from the husband, and emotional and practical support from the
      mother-in-law, declined more strongly in women with antenatal depressive
      symptoms; (iii) associations between depressive symptoms and worsening spouse
      relationship were more pronounced in traditional compared with nuclear families.
      CONCLUSIONS: Antenatal depressive symptoms predicted marked decline in the
      quality of key relationships over the postnatal period. This may account for some
      of the contemporaneous associations between depression and worse social support,
      and may compound the risk of perinatal depression in subsequent pregnancies.

PMID- 27873559
TI  - Educational achievement in psychiatric patients and their siblings: a register
      based study in 30 000 individuals in The Netherlands.
AB  - BACKGROUND: Poor educational achievement is associated with a range of
      psychiatric disorders. Several studies suggest that this underperformance is due
      to cognitive deficits that commence before disease onset and reflect a genetic
      risk for this disorder. However, the specificity and the familial contribution of
      this cognitive deficit are not clear. We analysed lifetime educational
      achievement of psychiatric patients diagnosed with schizophrenia, bipolar or
      depressive disorder and their unaffected siblings. METHOD: In a register-based
      case-control study, 1561 patients with schizophrenia, 813 patients with bipolar
      disorder, 8112 patients with depression, and their siblings were each matched
      with eight population controls. Patients, siblings and controls were compared on
      the highest educational stream they completed. RESULTS: Lower educational
      achievement was present in schizophrenia patients from primary school onwards
      [completing primary school: odds ratio (OR) 0.69; completing secondary school: OR
      0.69; completing academic education: OR 0.46], compared to patients with bipolar
      disorder or depression. Siblings of schizophrenia, bipolar or depressed patients
      showed no underachievement at primary or secondary school, but siblings of
      schizophrenia patients as well as siblings of depressed patients were less
      successful in their educational achievement after secondary school (completing
      academic education, schizophrenia siblings: OR 0.90; depressive disorder
      siblings: OR 0.91). CONCLUSIONS: Educational underachievement from primary school
      onwards is specifically related to schizophrenia and not to bipolar disorder or
      depression. Moreover, it appears to be a harbinger of the illness, since it is
      not found in their siblings. These results add to evidence that early cognitive
      deficits are a distinct feature of the schizophrenia phenotype.

PMID- 27873560
TI  - Embryonic development in Zungaro jahu.
AB  - The aim of this study was to characterize the embryonic development of Zungaro
      jahu, a fresh water teleostei commonly known as 'jau'. Samples were collected at
      pre-determined times from oocyte release to larval hatching and analysed under
      light microscopy, transmission electron microscopy and scanning electron
      microscopy. At the first collection times, the oocytes and eggs were spherical
      and yellowish, with an evident micropyle. Embryo development took place at 29.4
      +/- 1.5 degrees C and was divided into seven stages: zygote, cleavage, morula,
      blastula, gastrula, organogenesis, and hatching. The differentiation of the
      animal and vegetative poles occured during the zygote stage, at 10 min post
      fertilization (mpf), leading to the development of the egg cell at 15 mpf. From
      20 to 75 mpf, successive cleavages resulted in the formation of 2, 4, 8, 16, 32
      and 64 blastomeres. The morula stage was observed between 90 and 105 mpf, and the
      blastula and gastrula stage at 120 and 180 mpf; respectively. The end of the
      gastrula stage was characterized by the presence of the yolk plug at 360 mpf.
      Organogenesis followed, with differentiation of the cephalic and caudal regions,
      elongation of the embryo by the cephalo-caudal axis, and somitogenesis. Hatching
      occurred at 780 mpf, with mean larval total length of 3.79 +/- 0.11 mm.

PMID- 27873561
TI  - Antipsychotic drug exposure and risk of myocardial infarction.
AB  - Patients experiencing psychoses and in need of antipsychotic agents may be
      exposed to a higher risk of myocardial infarction (MI) than the general
      population. As there have been no randomised studies investigating this
      association, a recent systematic review and meta-analysis included all
      observational studies that compared the incidence of MI among patients receiving
      antipsychotics v. no treatment. It found nine studies and calculated that the
      odds (risk) for developing MI were 1.88-fold higher in antipsychotic users
      compared with individuals who had not taken antipsychotic drugs. In this
      commentary, the results of this systematic review are discussed in view of their
      clinical implications for everyday clinical practice.

PMID- 27873562
TI  - Validation of the Maslach Burnout Inventory-General Survey on a Representative
      Sample of Dominican Teachers: Normative Data.
AB  - Burnout is characterized by emotional exhaustion, depersonalization and lack of
      personal accomplishment (Bakke, Demerouti, & Sanz-Vergel, 2014). Several
      instruments for its measurement exist, but the most widely used scale for
      measuring its dimensions, by far, is the Maslach Burnout Inventory (MBI) in its
      different versions. Among the available versions of the scale, the MBI-General
      Survey was developed to measure three dimensions of burnout (cynicism, personal
      accomplishment, and emotional exhaustion) regardless of the type of work. The aim
      of this research is to offer evidence on the psychometric properties of the MBI
      GS for its use in the Dominican Republic and other Caribbean Spanish-speaking
      countries, using representative sample of Dominican teachers. The factorial
      validity was studied through confirmatory factor analysis. Several competing
      models were proved in order to test the dimensionality of the scale. The
      confirmatory analyses shown that the original three-factor structure had a
      superior fit, but item eleven was removed in order to get an excellent fit
      chi2(87) = 211.19, p < .001, CFI = .98, RMSEA = .038 90% CI [.032-.045].
      Regarding internal consistency, the CRI's are well above the cut-off criteria of
      .7 (CRI's ranged from .74 to .86). Concerning criterion-related validity, the
      three factors were correlated in the expected direction. Professional efficacy, a
      dimension of burnout measured in the opposite direction, was positively
      correlated with the three factors of work engagement, also as expected. This
      version was found to be a psychometrically sound measure of the three core
      dimensions of burnout.

PMID- 27873563
TI  - Comparative dynamics, seasonality in transmission, and predictability of
      childhood infections in Mexico.
AB  - The seasonality and periodicity of infections, and the mechanisms underlying
      observed dynamics, can have implications for control efforts. This is
      particularly true for acute childhood infections. Among these, the dynamics of
      measles is the best understood and has been extensively studied, most notably in
      the UK prior to the start of vaccination. Less is known about the dynamics of
      other childhood diseases, particularly outside Europe and the United States. In
      this paper, we leverage a unique dataset to examine the epidemiology of six
      childhood infections - measles, mumps, rubella, varicella, scarlet fever and
      pertussis - across 32 states in Mexico from 1985 to 2007. This dataset provides
      us with a spatio-temporal probe into the dynamics of six common childhood
      infections, and allows us to compare them in the same setting over the same time
      period. We examine three key epidemiological characteristics of these infections 
      the age profile of infections, spatio-temporal dynamics, and seasonality in
      transmission - and compare them with predictions from existing theory and past
      findings. Our analysis reveals interesting epidemiological differences between
      the six pathogens, and variations across space. We find signatures of term-time
      forcing (reduced transmission during the summer) for measles, mumps, rubella,
      varicella, and scarlet fever; for pertussis, a lack of term-time forcing could
      not be rejected.

PMID- 27873565
TI  - Patterns of virulence factor expression and antimicrobial resistance in
      Achromobacter xylosoxidans and Achromobacter ruhlandii isolates from patients
      with cystic fibrosis.
AB  - Achromobacter spp. are opportunistic pathogens increasingly recovered from adult
      patients with cystic fibrosis (CF). We report the characterization of 122
      Achromobacter spp. isolates recovered from 39 CF patients by multilocus sequence
      typing, virulence traits, and susceptibility to antimicrobials. Two species, A.
      xylosoxidans (77%) and A. ruhlandii (23%) were identified. All isolates showed a
      similar biofilm formation ability, and a positive swimming phenotype. By
      contrast, 4.3% and 44.4% of A. xylosoxidans and A. ruhlandii, respectively,
      exhibited a negative swarming phenotype, making the swimming and swarming
      abilities of A. xylosoxidans significantly higher than those of A. ruhlandii. A.
      xylosoxidans isolates from an outbreak clone also exhibited significantly higher
      motility. Both species were generally susceptible to ceftazidime, ciprofloxacin,
      imipenem and trimethoprim/sulphamethoxazole and there was no significant
      difference in susceptibility between isolates from chronic or sporadic infection.
      However, A. xylosoxidans isolates from chronic and sporadic cases were
      significantly more resistant to imipenem and ceftazidime than isolates of the
      outbreak clone.

PMID- 27873564
TI  - Effect of enhanced biosecurity and selected on-farm factors on Campylobacter
      colonization of chicken broilers.
AB  - Human campylobacteriosis is the most commonly reported gastrointestinal bacterial
      infection in the EU; poultry meat has been identified as the main source of
      infection. We tested the hypothesis that enhanced biosecurity and other factors
      such as welfare status, breed, the practice of partial depopulation and number of
      empty days between flocks may prevent Campylobacter spp. caecal colonization of
      poultry batches at high levels (>123 000 c.f.u./g in pooled caecal samples). We
      analysed data from 2314 poultry batches sampled at slaughter in the UK in 2011
      2013. We employed random-effects logistic regression to account for clustering of
      batches within farms and adjust for confounding. We estimated population
      attributable fractions using adjusted risk ratios. Enhanced biosecurity reduced
      the odds of colonization at partial depopulation [odds ratio (OR) 0.25, 95%
      confidence interval (CI) 0.14-0.47] and, to a lesser extent, at final
      depopulation (OR 0.47, 95% CI 0.25-0.89). An effect of the type of breed was also
      found. Under our assumptions, approximately 1/3 of highly colonized batches would
      be avoided if they were all raised under enhanced biosecurity or without partial
      depopulation. The results of the study indicate that on-farm measures can play an
      important role in reducing colonization of broiler chickens with Campylobacter
      spp. and as a result human exposure.

PMID- 27873566
TI  - Pathological and phylogenetic characterization of Amphibiothecum sp. infection in
      an isolated amphibian (Lissotriton helveticus) population on the island of Rum
      (Scotland).
AB  - Outbreaks of cutaneous infectious disease in amphibians are increasingly being
      attributed to an overlooked group of fungal-like pathogens, the Dermocystids.
      During the last 10 years on the Isle of Rum, Scotland, palmate newts (Lissotriton
      helveticus) have been reportedly afflicted by unusual skin lesions. Here we
      present pathological and molecular findings confirming that the pathogen
      associated with these lesions is a novel organism of the order Dermocystida, and
      represents the first formally reported, and potentially lethal, case of amphibian
      Dermocystid infection in the UK. Whilst the gross pathology and the parasite cyst
      morphology were synonymous to those described in a study from infected L.
      helveticus in France, we observed a more extreme clinical outcome on Rum
      involving severe subcutaneous oedema. Phylogenetic topologies supported synonymy
      between Dermocystid sequences from Rum and France and as well as their
      distinction from Amphibiocystidium spp. Phylogenetic analysis also suggested that
      the amphibian-infecting Dermocystids are not monophyletic. We conclude that the
      L. helveticus-infecting pathogen represents a single, novel species;
      Amphibiothecum meredithae.

PMID- 27873567
TI  - Early germinal vesicle breakdown is a predictor of high preimplantation
      developmental competent oocytes in mice.
AB  - The preselection of highly developmentally competent oocytes for in vitro
      maturation (IVM) is crucial for improving assisted reproductive technology.
      Although several intrinsic markers of oocyte quality are known to be closely
      related to the onset of nuclear maturation (germinal vesicle break down, GVBD), a
      direct comparison between GVBD timing and oocyte quality has never been reported.
      In this study, we established a non-invasive oocyte evaluation method based on
      GVBD timing for preselecting more developmental competent oocytes in mice.
      Because the O2 concentration during IVM may affect the nuclear kinetics, all
      experiments were performed under two distinct O2 concentrations: 20% and 5% O2.
      First, we determined the time course of changes in nuclear maturation and
      preimplantation developmental competence of in vitro-matured oocytes to estimate
      GVBD timing in high developmental competent oocytes. Two-thirds of oocytes that
      underwent GVBD in early IVM seemed to mainly contribute to the blastocyst yield.
      To confirm this result, we compared the preimplantation developmental competence
      of the early and late GVBD oocytes. Cleavage and blastocyst formation rates of
      early GVBD oocytes (80.2% and 52.7% under 20% O2, respectively, and 67.6% and
      47.3% under 5% O2, respectively) were almost double those of late GVBD oocytes
      (44.8% and 26.0% under 20% O2, respectively, and 40.4% and 17.9% under 5% O2,
      respectively). With no observable alterations by checking the timing of GVBD in
      preimplantation developmental competence, oocyte evaluation based on GVBD timing
      can be used as an efficient and non-invasive preselection method for high
      developmental competent oocytes.

PMID- 27873568
TI  - Can Big Five Facets Distinguish between Hedonic and Eudaimonic Well-Being? A
      Dominance Analysis.
AB  - In this study, the aim was to analyze the relative importance of Five-Factor
      Model (FFM) personality facets for eudaimonic or psychological well-being (PWB)
      and hedonic or subjective well-being (SWB) through dominance analyses. The
      participants were 1,403 adult residents of Spain (mean age 37.2 years, SD =
      13.9). As expected, facets captured a substantial proportion of the variance in
      PWB and SWB, with PWB being better predicted than SWB (explaining around 36-55%
      of the variance of PWB vs. 25% of the variance of SWB). Some facets were common
      to both types of well-being such as depression (explaining between 5-33% of the
      variance), vulnerability (explaining between 4-21% of the variance), positive
      emotions (explaining between 2-9% of the variance) and achievement striving
      (explaining between 2-10% of the variance), whereas others made a unique
      contribution according to type of well-being. Certain facets had a greater
      relative importance for women's well-being -e.g., positive emotions explained 9%
      of the variance of self-acceptance for women vs. 3% for men- and others for men's
      well-being -e.g., achievement striving explained 9% of the variance of personal
      growth for men vs. 2% for women-. The present results contribute to the
      literature by identifying which Big Five facets showed greater relative
      importance in explaining and distinguishing between PWB and SWB for women and
      men.

PMID- 27873569
TI  - Establishing a Standard of Care for Deep Brain Stimulation Centers in Canada.
AB  - During the "DBS Canada Day" symposium held in Toronto July 4-5, 2014, the
      scientific committee invited experts to share their knowledge regarding deep
      brain stimulation (DBS) management of movement disorders in three domains: (1)
      the programming algorithms, (2) the necessary team to run a neurosurgery program,
      and (3) the appropriate scales to better define in a more comprehensive fashion
      the effect of the brain surgery. Each presentation was followed by an open
      discussion, and this article reports on the conclusions of this meeting on these
      three questions. Concerning programming, the role of the pulse width and the
      switching off of the stimulation at night for thalamic stimulation for the
      control of tremor have been discussed. The algorithms proposed in the literature
      for programming in Parkinson's disease (PD) need validation. In dystonia, the use
      of monopolar vs bipolar parameters, the use of low vs high frequencies and the
      use of smaller versus larger pulse widths all need to be examined properly.
      Concerning the necessary team to run a neurosurgical program, recommendations
      will follow the suggestions for standardized outcome measures. Regarding the
      outcome measures for DBS in PD, investigations need to focus on the non-motor
      aspects of PD. Identifying which nonmotor symptoms respond to DBS would allow a
      better screening before and satisfaction postoperatively. There is an important
      need for more data to determine the optimal programming protocol and the standard
      measures that should be performed routinely by all centers.

PMID- 27873570
TI  - Dissecting aneurysm of the interventricular septum due to rupture of the sinus of
      Valsalva.
AB  - Aneurysm of the sinus of Valsalva is a rare congenital cardiac anomaly. It occurs
      as an outpouching that progresses like a windsock, and it may rupture producing
      aortic regurgitation, cardiac tamponade, congestive heart failure, conduction
      abnormalities, and stroke. We describe a case of rupture of the sinus of Valsalva
      into the interventricular septum producing a large dissecting aneurysm. Despite
      the location, it did not produce a conduction abnormality.

PMID- 27873571
TI  - The determinants of defensive medicine practices in Belgium.
AB  - In 2010 the Belgian government introduced a low cost administrative procedure for
      compensating medical injuries to overcome the major shortcomings of the existing
      tort system. This paper examines, for the first time, to what extent this reform
      had an impact on physician specialists' defensive practices and what are the
      relevant determinants affecting physicians' clinical decision making. Based on a
      survey of 508 physicians, we find evidence of a relatively modest increase in
      defensive practices among physicians in various specialties. In general, 14% of
      the respondents, who were aware of the reform, reported to have increased their
      overall defensive behaviour, while respectively 18 and 13% altered their
      assurance and avoidance behaviour. Commonly used physician characteristics, such
      as claims experience and gender, have a similar impact on defensive medicine as
      documented in existing literature. Furthermore, the determinant physician's
      access to an incident reporting system is found to have a significant impact on
      most of the defensive medicine measures. Health care institutions may therefore
      play an important role in controlling and reducing physicians' defensive
      practices.

PMID- 27873572
TI  - Risk assessment of dengue fever in Zhongshan, China: a time-series regression
      tree analysis.
AB  - Dengue fever (DF) is the most prevalent and rapidly spreading mosquito-borne
      disease globally. Control of DF is limited by barriers to vector control and
      integrated management approaches. This study aimed to explore the potential risk
      factors for autochthonous DF transmission and to estimate the threshold effects
      of high-order interactions among risk factors. A time-series regression tree
      model was applied to estimate the hierarchical relationship between reported
      autochthonous DF cases and the potential risk factors including the timeliness of
      DF surveillance systems (median time interval between symptom onset date and
      diagnosis date, MTIOD), mosquito density, imported cases and meteorological
      factors in Zhongshan, China from 2001 to 2013. We found that MTIOD was the most
      influential factor in autochthonous DF transmission. Monthly autochthonous DF
      incidence rate increased by 36.02-fold [relative risk (RR) 36.02, 95% confidence
      interval (CI) 25.26-46.78, compared to the average DF incidence rate during the
      study period] when the 2-month lagged moving average of MTIOD was >4.15 days and
      the 3-month lagged moving average of the mean Breteau Index (BI) was ?16.57. If
      the 2-month lagged moving average MTIOD was between 1.11 and 4.15 days and the
      monthly maximum diurnal temperature range at a lag of 1 month was <9.6  degrees
      C, the monthly mean autochthonous DF incidence rate increased by 14.67-fold (RR
      14.67, 95% CI 8.84-20.51, compared to the average DF incidence rate during the
      study period). This study demonstrates that the timeliness of DF surveillance
      systems, mosquito density and diurnal temperature range play critical roles in
      the autochthonous DF transmission in Zhongshan. Better assessment and prediction
      of the risk of DF transmission is beneficial for establishing scientific
      strategies for DF early warning surveillance and control.

PMID- 27873575
TI  - A qualitative study on the impact of internalized stigma on type 2 diabetes self
      management.
AB  - OBJECTIVE: To explore how patients with type 2 diabetes (T2DM) psychologically
      and behaviorally respond to internalized stigma through social stigma. METHODS: A
      qualitative study with semi-structured interviews was recorded on audiotapes,
      transcribed verbatim, and analyzed using a grounded theory approach. Participants
      were adults aged 30-64 years and diagnosed with T2DM. A total of 26 patients
      participated. RESULTS: The qualitative data revealed that participants' responses
      to social stigma, although varied, could be organized into a four-step process:
      Encountering Negative Experiences, Reevaluating the Self with Type 2 Diabetes,
      Reconstructing a Sense of Identity, and Maintaining Balance between Patient and
      Social Roles. When participants form a negative image of and relationship to
      their illness, they tend to internalize stigma, which can affect their sense of
      self-worth, attitude toward social participation, and compliance. CONCLUSION:
      Participants who internalize stigma tend to have a lower sense of self-worth and
      their social participation falls somewhere between severely limited (Social
      Avoidance) and highly active (Role Conflict). This can hinder devotion to their
      treatment regimen and affect their degree of compliance with physicians. PRACTICE
      IMPLICATIONS: Internalized stigma can be assessed by observing a patient's
      illness-related negative self-image.

PMID- 27873574
TI  - Postprandial sleep mechanics in Drosophila.
AB  - Food consumption is thought to induce sleepiness. However, little is known about
      how postprandial sleep is regulated. Here, we simultaneously measured sleep and
      food intake of individual flies and found a transient rise in sleep following
      meals. Depending on the amount consumed, the effect ranged from slightly arousing
      to strongly sleep inducing. Postprandial sleep was positively correlated with
      ingested volume, protein, and salt-but not sucrose-revealing meal property
      specific regulation. Silencing of leucokinin receptor (Lkr) neurons specifically
      reduced sleep induced by protein consumption. Thermogenetic stimulation of
      leucokinin (Lk) neurons decreased whereas Lk downregulation by RNAi increased
      postprandial sleep, suggestive of an inhibitory connection in the Lk-Lkr circuit.
      We further identified a subset of non-leucokininergic cells proximal to Lkr
      neurons that rhythmically increased postprandial sleep when silenced, suggesting
      that these cells are cyclically gated inhibitory inputs to Lkr neurons. Together,
      these findings reveal the dynamic nature of postprandial sleep.

PMID- 27873576
TI  - Assessment of combination therapy by time kill curve analysis and chequerboard
      assay for treatment of multi-drug resistant Pseudomonas aeruginosa isolates.
AB  - Multidrug resistant Pseudomonas aeruginosa is a major nosocomial pathogen, and
      effective therapy presents a great clinical challenge. Combination therapy,
      employing pre-existing antibiotics, is an attractive approach for the treatment
      of such infections which may also curtail drug resistance. This study was
      undertaken with the objectives to assess the synergy of five different
      antimicrobial combinations (piperacillin-tazobactum with levofloxacin,
      cefoperazone-sulbactum with levofloxacin, piperacillin-tazobactum with amikacin,
      cefoperazone-sulbactum with amikacin and amikacin with levofloxacin for the
      treatment of Pseudomonas aeruginosa isolates with varied susceptibility profile
      by time kill curve assay and the chequerboard technique. In our study concordance
      between these two methods was noted in 71.7% isolates tested. Le-Pt combination
      demonstrated maximum synergy (72.7%), followed by Ak-Le (66.7%) and Ak-Cfs (60%)
      combination. Le-Cfs and Ak-Pt however, showed synergy in significantly lower
      number of isolates. However, at sub-MIC concentrations Ak-Pt combination was
      found to be most effective. Synergy between different drugs should be routinely
      monitored for exploring more feasible treatment options and to prevent the
      emergence of multi-drug resistant strains. Piperacillin-tazobactum emerged as a
      versatile drug whose potential should be explored with other drugs for
      combination treatment of P. aeruginosa isolates.

PMID- 27873573
TI  - POWERDRESS interacts with HISTONE DEACETYLASE 9 to promote aging in Arabidopsis.
AB  - Leaf senescence is an essential part of the plant lifecycle during which
      nutrients are re-allocated to other tissues. The regulation of leaf senescence is
      a complex process. However, the underlying mechanism is poorly understood. Here,
      we uncovered a novel and the pivotal role of Arabidopsis HDA9 (a RPD3-like
      histone deacetylase) in promoting the onset of leaf senescence. We found that
      HDA9 acts in complex with a SANT domain-containing protein POWERDRESS (PWR) and
      transcription factor WRKY53. Our genome-wide profiling of HDA9 occupancy reveals
      that HDA9 directly binds to the promoters of key negative regulators of
      senescence and this association requires PWR. Furthermore, we found that PWR is
      important for HDA9 nuclear accumulation. This study reveals an uncharacterized
      epigenetic complex involved in leaf senescence and provides mechanistic insights
      into how a histone deacetylase along with a chromatin-binding protein contribute
      to a robust regulatory network to modulate the onset of plant aging.

PMID- 27873577
TI  - Vancomycin resistance in Streptomyces coelicolor is phosphate-dependent but is
      not mediated by the PhoP regulator.
AB  - Vancomycin is an essential antibiotic to treat infections caused by multidrug
      resistant bacteria. Several bacteria show resistance to vancomycin, including the
      model actinomycete Streptomyces coelicolor. In this study, vancomycin disk
      diffusion tests were performed to determine vancomycin resistance in S.
      coelicolor M145 under rich (TSA medium) or defined (MMCGT medium) growth
      conditions. A vancomycin-susceptible phenotype was observed when the TSA rich
      medium was used, whereas a resistant phenotype was obtained when the low
      phosphate MMCGT medium was used. To identify which component was responsible for
      the vancomycin-resistant phenotype, all the components of the MMCGT medium were
      added individually to the TSA medium, and vice versa. Addition of phosphate to
      the MMCGT medium (the phosphate concentration is much higher in TSA than in
      MMCGT) produced a vancomycin-susceptible phenotype in MMCGT. Phosphate regulation
      of vancomycin resistance is not PhoP-dependent since the same minimum inhibitory
      concentrations were obtained in S. coelicolor parental and DeltaphoP mutant
      strains. This phosphate regulation was not observed in the vancomycin-producer
      Amycolatopsis orientalis NRRL 2452, which was always resistant both in TSA and
      MMCGT (with or without phosphate addition) media. On the other hand, other
      Streptomyces spp. were susceptible to vancomycin in all conditions tested,
      including Streptomyces toyocaensis, the producer of a glycopeptide antibiotic
      different from vancomycin. In conclusion, the phosphate concentration clearly
      affects the resistance of S. coelicolor to vancomycin.

PMID- 27873578
TI  - Nosocomial dissemination of Providencia stuartii isolates producing extended
      spectrum beta-lactamases VEB-1 and SHV-5, metallo-beta-lactamase VIM-1, and RNA
      methylase RmtB.

PMID- 27873579
TI  - Public health impact and antimicrobial selection of meticillin-resistant
      staphylococci in animals.
AB  - Whilst meticillin-resistant Staphylococcus aureus (MRSA) infections reported
      sporadically in companion animals and cattle in the 1970s were probably of human
      origin, the recently emerged livestock-associated MRSA (LA-MRSA) and meticillin
      resistant Staphylococcus pseudintermedius (MRSP) strains clearly have animal
      origins and their isolation from humans is usually associated with exposure to
      livestock and companion animals, respectively. LA-MRSA is primarily an
      occupational health risk to farm workers and veterinarians. The risk that this
      zoonotic agent may spread in the community is particularly acute in countries
      with high livestock production and low MRSA prevalence in the human population.
      MRSP is primarily a threat to animal health, and cases of human infection are
      rare but may be overlooked in diagnostic laboratories. There is no conclusive
      evidence of antimicrobial selection associated with the sudden emergence of LA
      MRSA and MRSP. However, the rapid global spread of these bacteria has presumably
      been favoured by antimicrobial selective pressure. Tetracyclines, zinc and
      extended-spectrum cephalosporins (including extra-label use) are the most likely
      selective drivers implicated in the spread of LA-MRSA, whilst increased use of
      broad-spectrum beta-lactams and fluoroquinolones, partly enhanced by extra-label
      use and the introduction of cheap generics, may have played an important role in
      the rapid dissemination of MRSP. Control of LA-MRSA and MRSP requires a dual
      approach aimed at reducing antimicrobial consumption and preventing transmission
      between animals and from animals to humans or vice versa. Restricted use of
      fluoroquinolones and cephalosporins in livestock, and national practice
      guidelines for rational antimicrobial use both in food and companion animals are
      warranted.

PMID- 27873580
TI  - Global antibacterial resistance: The never-ending story.
AB  - Bacterial resistance is undoubtedly recognised as a major medical challenge in
      most healthcare systems. Resistance-determining genes, mostly in combination, and
      multidrug-resistant (MDR) pathogens are spreading with unprecedented speed. Well
      known resistance carriers with high clinical impact include the Gram-positive
      organisms Staphylococcus aureus and Enterococcus spp. In contrast to these
      organisms that are usually still treatable with newer alternative antibacterial
      drugs, some Gram-negative bacteria, especially Escherichia coli, Klebsiella
      pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp., have developed
      resistance to most or all available antibiotics. Such strains are already a
      reality in some Mediterranean and Asian countries. According to their resistance
      epidemiology (based on major drivers favouring resistance), three regions are
      pinpointed as high-impact resistance hot spots. Despite the clear medical need
      for novel antibiotics without cross-resistance issues, antibacterial research and
      development pipelines are nearly dry, thus failing to provide the flow of novel
      antibiotics required to match the fast emergence and spread of MDR bacteria. In a
      globalised world, only concerted global actions can mitigate a future with
      untreatable infectious diseases.

PMID- 27873581
TI  - Central venous catheter-related biofilm infections: An up-to-date focus on
      meticillin-resistant Staphylococcus aureus.
AB  - Central venous catheters are indispensable for the long-term treatment of
      seriously and chronically ill patients, but their use is often associated with a
      variety of complications; indeed, 90% of primary bloodstream infections are
      related to patients having a catheter. In studies performed in France, Germany
      and Italy, meticillin-resistant Staphylococcus aureus (MRSA) accounted for >50%
      of all S. aureus isolates obtained in catheter-related bloodstream infections
      (CRBSIs). These infections have a serious impact on long-term disability of the
      patient, a substantial additional financial burden for health systems, and high
      costs for patients. Decreasing the rate of CRBSIs requires a multidisciplinary
      approach, including behavioural and educational interventions and the insertion
      of the correct type of catheter. Although vancomycin remains the cornerstone of
      empirical therapy for CRBSIs caused by MRSA, combination of different
      antimicrobials and new approaches are indispensable to enhance the eradication of
      S. aureus biofilms and to manage the patient appropriately.

PMID- 27873582
TI  - Wound infections caused by inducible meticillin-resistant Staphylococcus aureus
      strains.
AB  - Detection of meticillin resistance in Staphylococcus aureus isolates continues to
      be a challenge. Clinical specimens obtained from abscesses from two
      epidemiologically unrelated outpatients were positive for meticillin-resistant S.
      aureus (MRSA) by a commercial PCR assay, but colonies obtained by culture were
      susceptible to oxacillin by an automated testing method. The colonies were also
      negative using a penicillin-binding protein 2a (PBP2a) latex agglutination test.
      Because of the discrepancy between the genotypic and phenotypic results, both
      isolates were re-tested by PCR, disc diffusion, VITEK(r) 2 and MicroScan(r) and
      were plated on chromogenic agar. Both isolates also underwent cefoxitin induction
      for additional susceptibility testing studies. Following overnight induction with
      cefoxitin, both isolates demonstrated resistance to oxacillin and cefoxitin by
      the two automated methods and by disc diffusion, and were positive using PBP2a
      latex agglutination tests. Population analysis failed to identify heteroresistant
      subpopulations in uninduced isolates. Identifying the presence of MRSA by PCR
      directly in the specimens was critical for determining the appropriate course of
      antimicrobial therapy for the patients. Both infections resolved with non-beta
      lactam therapy.

PMID- 27873583
TI  - Laboratory evaluation of BrillianceTM CRE Agar for screening carbapenem-resistant
      Enterobacteriaceae: Performance on a collection of characterised clinical
      isolates from Greece.
AB  - The performance of Oxoid BrillianceTM CRE Agar (BCRE), a new chromogenic medium
      designed for screening of carbapenem-resistant Enterobacteriaceae, was evaluated
      on a collection of clinical isolates of enterobacteria (n=175) and non-fermenters
      (n=55) with known beta-lactam resistance mechanisms and levels of susceptibility
      to carbapenems. BCRE supported the growth of 100 of 108 enterobacterial isolates
      that were non-susceptible to at least one carbapenem, whilst excluding 57 of the
      67 carbapenem-susceptible isolates. The eight non-susceptible isolates that did
      not grow on BCRE were carbapenemase-producers with low carbapenem minimum
      inhibitory concentrations, mostly exhibiting non-susceptibility only to one
      carbapenem. In total, of 107 carbapenemase-producing enterobacteria that were
      included in the study, 16 did not grow, with most of them being either
      susceptible (n=8) or intermediate-susceptible (n=5) to carbapenems. Regarding the
      10 carbapenem-susceptible enterobacteria that were not excluded by BCRE, 1
      produced a carbapenemase and the rest possessed strong backgrounds of various
      other beta-lactam resistance mechanisms. The medium allowed growth of almost all
      carbapenem-resistant non-fermenting isolates; nevertheless, non-fermenters were
      clearly differentiated from Enterobacteriaceae by colony colour and morphology.

PMID- 27873585
TI  - Biocide susceptibility in bifidobacteria of human origin.
AB  - Disinfectants have been used in a variety of environmental applications, in
      products for personal care and in the food industry. The food industry has
      increased the use of biocides and chemical-based disinfectants to control
      microbial ecology at production sites in an effort to improve hygiene measures
      and food safety. However, the susceptibility profile of micro-organisms to
      disinfectants has been largely neglected. This study therefore aimed to provide
      this type of information by focusing on the four most commonly used biocides in
      the food industry, determining their minimum inhibitory concentrations (MICs) and
      analysing the distribution of MICs across a variety of micro-organisms. In total,
      99 different strains of Bifidobacterium spp. were studied. Results showed a
      unimodal distribution of MICs for chlorhexidine, triclosan (Irgasan) and sodium
      hypochlorite with no apparent species-specific correlation. Conversely, part of
      the tested bifidobacteria population (20%) showed reduced susceptibility to
      benzalkonium chloride compared with the susceptibility exhibited by the majority
      of the tested bacterial community. The highest MICs were distributed among almost
      all of the considered Bifidobacterium spp. In generally, the sensitivity of the
      studied strains to the four tested biocides appeared to be a genus-related trait.

PMID- 27873584
TI  - Analysis of the influence of drug resistance factors on the efficacy of
      combinations of antibiotics for multidrug-resistant Pseudomonas aeruginosa
      isolated from hospitals located in the suburbs of Kanto area, Japan.
AB  - Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa are very
      difficult to treat. The aim of this study was to develop more effective
      treatments by investigating in vitro the effects of combinations of antibiotics
      against 47 MDR P. aeruginosa isolates harbouring various resistance factors. The
      isolates included 41 (87%) metallo-beta-lactamase (MBL)-positive strains, 37
      (79%) strains with mutations in OprD and 46 (98%) strains carrying the genes
      encoding aminoglycoside-modifying enzymes (AMEs). The quinolone resistance
      determining region was mutated in all of the strains. These strains were
      classified into 16 groups according to amplified fragment length polymorphism and
      resistance factors. The effects of combinations of antibiotics on 16
      representative strains were determined using a 'Break-point Checkerboard Plate'
      assay. Combinations of amikacin+aztreonam (coverage rate, 81.3%) and
      arbekacin+aztreonam (93.8%) inhibited growth. In contrast, combinations of
      ciprofloxacin+meropenem (6.3%) and ciprofloxacin+ceftazidime (12.5%) were much
      less effective. Aztreonam and arbekacin (or amikacin) are not substrates for MBLs
      and AMEs, respectively. We conclude that the combined effects of these drugs were
      possibly because of resistance factors.

PMID- 27873586
TI  - NRTI-sparing regimens yield higher rates of drug resistance than NRTI-based
      regimens for HIV-1 treatment.
AB  - To treat human immunodeficiency virus (HIV)-infected patients, international
      guidelines recommend the combination of two nucleos(t)ide reverse transcriptase
      inhibitors [N(t)RTIs] and a third agent [non-NRTI (NNRTI), boosted protease
      inhibitor (r/PI) or integrase inhibitor (INI)] for initial treatment. The
      objective of this study was to compare the selection of resistance to
      antiretrovirals (ARVs) for regimens containing or lacking N(t)RTIs in patients
      experiencing their first virological failure. Eligible patients had a first
      virological failure, defined as the occurrence of two consecutive HIV plasma
      viral loads >=50copies/mL. Genotypic resistance testing was performed at the time
      of virological failure (on the second sample with detectable viral load
      >=50copies/mL) in patients failing regimens of N(t)RTIs+r/PI or NNRTI or INI,
      r/PI+NNRTI or INI, and INI+NNRTI. Among 434 virological failures analysed,
      resistance testing results were available in 416 cases (95.9%). Higher rates of
      drug resistance were observed in patients receiving N(t)RTI-sparing regimens.
      When the combination of N(t)RTIs+r/PI was used, PIs protect themselves and the
      associated N(t)RTIs from the selection of resistance; however, this was not
      observed with the NNRTI+r/PI combination. The same phenomenon was observed for
      raltegravir: when used in combination with N(t)RTIs, INI resistance mutations
      were less frequently selected compared with its use in combination with PIs or
      NNRTIs. In conclusion, regimens of the ARV classes combined impact the frequency
      of resistance development. Lower resistance is observed for N(t)RTI-based
      regimens, with more therapeutic options for subsequent regimens after failure.

PMID- 27873587
TI  - Costs and length of stay associated with extended-spectrum beta-lactamase
      production in cases of Escherichia coli bloodstream infection.
AB  - The prevalence of infections with extended-spectrum beta-lactamase (ESBL)
      producing bacteria is increasing worldwide. The economic burden of this
      development has not yet been sufficiently studied. Therefore, this study on
      hospital costs and length of stay (LoS) associated with cases of bloodstream
      infection (BSI) due to ESBL-producing Escherichia coli was performed. A matched
      case-control study of patients with E. coli BSI between 2008 and 2010 in Charite
      University Hospital (Berlin, Germany) was performed. Cases were patients with
      ESBL-producing E. coli BSI and controls were patients with ESBL-negative E. coli
      BSI. Cases and controls were matched in a 1:1 ratio by age +/-5 years, sex,
      underlying co-morbidities, LoS before BSI onset, and discharge year. In total,
      1098 consecutive patients with E. coli BSI were identified, comprising 115
      (10.5%) ESBL-positive and 983 (89.5%) ESBL-negative. Of the 115 ESBL-positive
      infections 67 (58.3%) were hospital-acquired in contrast to 382/983 (38.9%) of
      the ESBL-negative infections (P<0.001). After matching for confounders, there
      were no significant differences in costs, LoS or mortality between ESBL-positive
      and ESBL-negative E. coli BSIs. In conclusion, patients with BSI due to ESBL
      producing E. coli were neither more costly nor stayed longer in the hospital than
      patients with BSI due to ESBL-negative E. coli.

PMID- 27873588
TI  - aac(6')-Ib-cr is the major plasmid-mediated quinolone resistance determinant in
      extended-spectrum beta-lactamase-producing Escherichia coli in eastern France.
AB  - The aim of this study was to describe the presence of plasmid-mediated quinolone
      resistance (PMQR) determinants in extended spectrum beta-lactamase-producing
      Escherichia coli (ESBL-Ec) in hospitals in eastern France. All ESBL-Ec isolated
      from May 2008 to April 2009 in nine hospitals in eastern France were collected
      and screened by PCR for the presence of PMQR genes. bla genes were identified by
      PCR and sequencing. Randomly chosen PMQR-positive ESBL-Ec isolates were
      characterised by pulsed-field gel electrophoresis (PFGE), multilocus sequence
      typing (MLST) and phylogenetic group identification. Of the 447 ESBL-Ec tested,
      122 (27.3%) had a PMQR determinant. aac(6')-Ib-cr was more prevalent (118/122;
      96.7%) than qnr [4/122 (3.3%), comprising 2 qnrB2, 1 qnrB1 and 1 qnrA1]. Among 37
      PMQR-positive ESBL-Ec isolates selected for typing, 26 (70%) carried blaCTX-M-15
      of which 25/26 (96%) co-harboured aac(6')-Ib-cr. Of the 37 isolates, 14 belonged
      to the B2:ST131 clone, all of which produced AAC(6')-Ib-cr. On the other hand,
      most of the qnr genes (3/4) were observed in strains carrying bla genes other
      than blaCTX-M (qnrB2 and blaSHV-12; qnrA1 and blaTEM-52). These findings suggest
      that aac(6')-Ib-cr, rather than qnr, is the spreading PMQR determinant in ESBL-Ec
      isolates, and the qnr determinant is not specifically associated with blaCTX-M
      genes in France. aac(6')-Ib-cr was the predominant PMQR gene in ESBL-Ec isolated
      in eastern France hospitals, suggesting that the distribution may be due to
      clonal spread of ST131 CTX-M-15-producing E. coli isolates.

PMID- 27873589
TI  - Diversity of vancomycin-resistant enterococci in a low endemicity area.
AB  - Although vancomycin-resistant enterococci (VRE) are frequent nosocomial pathogens
      worldwide, in Japan their prevalence is low and their molecular epidemiology
      remains unclear. In The University of Tokyo Hospital (Tokyo, Japan), only five
      isolates of VRE (vanA-type Enterococcus faecium) were identified in the 20 years
      before 2010; however, nine isolates of vanB-type E. faecium were identified from
      2011 to 2012. Multilocus sequence typing (MLST) revealed that they belonged to
      five sequence types (ST18, ST78, ST203, ST412 and ST612). Despite the limited
      isolation, including one from a medical tourist, there was significant diversity
      in genotypes. Increasing medical travel might enhance the diversity of VRE.

PMID- 27873590
TI  - Characterisation of clinical canine meticillin-resistant and meticillin
      susceptible Staphylococcus pseudintermedius in France.
AB  - Staphylococcus pseudintermedius is a frequent pathogen in dogs. The emergence of
      meticillin-resistant S. pseudintermedius (MRSP), which is concomitantly resistant
      to nearly all veterinary licensed antibiotics used for systemic treatment in
      dogs, is a major problem for veterinarians. In France, 16.9% (41/243) of the S.
      pseudintermedius collected in 2010 were MRSP. They mainly belonged to the
      multiresistant MLST sequence type ST71, spa type t02, SCCmec type II-III (ST71
      t02-II-III) European clone. Moreover, we also report the emergence of
      multiresistant meticillin-susceptible S. pseudintermedius isolates presenting
      atypical and/or new spa types. This study highlights the need for surveillance,
      optimised treatment guidelines and new therapeutic alternatives.

PMID- 27873591
TI  - Detection of mutations in the katG gene among isoniazid-resistant Mycobacterium
      tuberculosis isolates from Lebanon and Syria.

PMID- 27873592
TI  - An interactive, point-of-care, computerised antibiotic prescription decision
      support system and quality of antibiotic prescription in the management of
      complicated urinary tract infection.

PMID- 27873594
TI  - First report of a clinical isolate of Leclercia adecarboxylata harbouring
      multiple resistance genes in Uruguay and review of the literature.
AB  - Here we report the detection of a Leclercia adecarboxylata strain, isolated from
      a case of osteomyelitis, harbouring multiple antibiotic resistance genes encoded
      on a 450-kb IncHI1/HI2 conjugative plasmid (pLa12). The plasmid carried a complex
      class 1 integron with the genetic array intI1-aac(6')-Ib-cr-blaOXA-1-catB3-arr3
      qacEDelta1-sul1-ISCR1; in addition, a blaDHA-1-like allele linked to ampR
      qacEDelta1-sul1 as well as blaSHV-12, blaTEM-1 and qnrB4-like genes were found.
      To the best of our knowledge, this is the first report of L. adecarboxylata
      harbouring transferable resistance genes to quinolones, chloramphenicol and
      rifampicin as well as a plasmidic class C beta-lactamase.

PMID- 27873593
TI  - Meticillin-resistant Staphylococcus aureus (MRSA) update: New insights into
      bacterial adaptation and therapeutic targets.
AB  - Successful meticillin-resistant Staphylococcus aureus (MRSA) clones have evolved
      to adapt to healthcare, community and livestock environments. This review will
      bring together recent studies into clone adaptation and the importance of genes
      acquired during horizontal gene transfer to survival in specific environments. It
      will also discuss the role of global regulators controlling virulence gene
      expression and resistance to antibiotics, such as the agr and vraRS systems.
      Understanding these processes in successful clones could reveal novel targets for
      therapeutic agents, which are urgently required to reduce the infection burden
      and improve treatment options.

PMID- 27873595
TI  - Association of some virulence genes with antibiotic resistance among
      uropathogenic Escherichia coli isolated from urinary tract infection patients in
      Alexandria, Egypt: A hospital-based study.
AB  - Uropathogenic Escherichia coli (UPEC) is the infecting agent most frequently
      involved in urinary tract infections (UTIs) worldwide. UPEC resistance to
      commonly used antibiotics represents a major health problem all over the world.
      Several factors have been associated with UPEC resistance to antibiotics. The
      present study deployed a molecular approach to explore the association between
      some UPEC virulence genes and antibiotic resistance among patients with UTI in
      Alexandria, Egypt. The study revealed a significant association between presence
      of the pap gene and resistance to gentamicin; however, it was not significantly
      associated with resistance to beta-lactam antibiotics, quinolones,
      aminoglycosides, nitrofurantoin and trimethoprim/sulfamethoxazole. The genes sfa,
      aer and cnf1 were not significantly associated with UPEC resistance to any of the
      tested antibiotics. In conclusion, resistance of UPEC isolates in the present
      study could be attributed to other virulence factors.

PMID- 27873596
TI  - Changing plasmid types responsible for extended-spectrum cephalosporin resistance
      in Escherichia coli O157:H7 in the USA, 1996-2009.
AB  - Escherichia coli O157 is a major cause of food-borne illness. Plasmids are
      genetic elements that mobilise antimicrobial resistance determinants, including
      blaCMY beta-lactamases that confer resistance to extended-spectrum cephalosporins
      (ESCs). ESCs are important for treating a variety of infections. IncA/C plasmids
      are found among diverse sources, including cattle, the principal source of E.
      coli O157 infections in humans. IncI1 plasmids are common among E. coli and
      Salmonella from poultry and other avian sources. To broaden our understanding of
      the reservoirs of blaCMY, the types of plasmids carrying blaCMY among E. coli
      O157 were determined. From 1996 to 2009, 3742 E. coli O157 isolates were tested.
      Eleven isolates (0.29%) were ceftriaxone-resistant and had a blaCMY-2-containing
      plasmid. All four isolates submitted before 2001 as well as a single 2001 isolate
      had blaCMY encoded on IncA/C plasmids, whilst all five isolates submitted after
      2001 and a single 2001 isolate had blaCMY carried on IncI1 plasmids. The IncI1
      plasmids were ST2, ST20 and ST23. We conclude that cephalosporin resistance among
      E. coli O157:H7 is due to plasmid-encoded blaCMY genes and that plasmid types
      appear to have shifted from IncA/C to IncI1. This shift suggests either a change
      in plasmid type among animal reservoirs or that the organism has expanded into
      avian reservoirs. More analysis of human, retail meat and food animal isolates is
      necessary to broaden our understanding of the antimicrobial resistance
      determinants of ESC resistance among E. coli O157.

PMID- 27873597
TI  - Detection of NDM-2-producing Acinetobacter baumannii and VIM-producing
      Pseudomonas aeruginosa in Palestine.
AB  - The aim of this study was to screen for carbapenem-resistant Gram-negative
      bacteria in Palestine and subsequently to identify and investigate the mechanisms
      of resistance. For a period of 6 weeks, all Gram-negative isolates were collected
      from six Palestinian hospital laboratories and were tested for susceptibility
      using 10MUg meropenem disks. Isolates showing resistance to meropenem were
      further investigated. The presence of carbapenemases was assessed by PCR. In
      addition, antimicrobial susceptibility testing, an efflux pump inhibitor assay
      and pulsed-field gel electrophoresis (PFGE) were performed. Isolates producing
      carbapenemases were further investigated by multilocus sequence typing (MLST). In
      total, 248 Gram-negative isolates were collected from the six laboratories. Among
      the 248 tested isolates, 15 Acinetobacter baumannii and 6 Pseudomonas aeruginosa
      were resistant to meropenem. One A. baumannii from Gaza produced NDM-2 and
      belonged to ST103. Thirteen of the carbapenem-resistant A. baumannii isolates
      possessed the intrinsic upregulated blaOXA-66 gene and one isolate carried blaOXA
      51. All but one of the OXA-66-producing A. baumannii belonged to ST2; the
      remaining isolate belonged to ST183. One of the carbapenem-resistant P.
      aeruginosa was classified as VIM-4-producing and three were VIM-2-producing
      isolates. The three VIM-2-producing isolates belonged to three new sequences
      types (ST1562, ST1563 and ST1564). All of the carbapenemase-producing isolates
      were multiresistant non-fermenters. To the best of our knowledge, this is the
      first report on NDM-producing A. baumannii and VIM-producing P. aeruginosa from
      Palestine.

PMID- 27873598
TI  - Surveillance trends of carbapenem-resistant Enterobacteriaceae from Singapore,
      2010-2013.
AB  - Trends in carbapenem-resistant Enterobacteriaceae (CRE) collected from hospitals
      nationwide in Singapore over 3 years are presented. Hospital isolates with
      imipenem or meropenem minimum inhibitory concentrations (MICs) of >1mg/L were
      sent to the National Public Health Laboratory for further investigation. A total
      of 400 CRE were submitted, 227 (56.8%) of which carried a carbapenemase gene.
      blaNDM was the most common (130/400; 32.5%), followed by blaOXA-48-like (blaOXA
      48, -181, -232) (55/400; 13.8%). Interestingly, four isolates bearing dual
      carbapenemase genes were also detected. KPC- and OXA-48-like-producing Klebsiella
      pneumoniae were fingerprinted by DiversiLab(r) rep-PCR. Locally, KPC producers do
      not appear to have clonal dissemination. In contrast, OXA-48-like producers were
      found to have a greater degree of clustering than KPC producers.

PMID- 27873599
TI  - Editorial.

PMID- 27873600
TI  - Basis for a cheap method for detecting bacteria and assessing their antibiotic
      susceptibility in urine samples.
AB  - Although molecular methods can now provide fast identification and the antibiotic
      susceptibility profile of infecting pathogens, these techniques are not
      affordable by a large majority of clinical laboratories in developing countries
      and can be considered excessive for simple, community-acquired infections. Most
      antibiotics are therefore prescribed empirically, which tends to avoid those
      drugs that face high resistance prevalence but that could still be used in a
      significant number of patients. This is a description of the basis for a fast,
      cheap method for assessing the presence of bacterial infection and its
      susceptibility to antibiotics in body fluids that are normally sterile, such as
      urine. The method is based on detecting a decreased concentration of glucose in
      liquid media as an indicator of bacterial growth, and the effect of antibiotics
      upon this change as an indicator of growth arrest by such antibiotics. The method
      can assess the presence of ca. 105CFU/mL in 4-6h as well as the presence of
      antibiotic resistance phenotypes of clinical relevance. The method was tested on
      20 clinical urine samples, comparing its results with conventional culture and
      susceptibility assays; results of both the proposed method and the
      culture/antibiogram were in agreement in all cases. Materials needed for this
      method would cost no more than US$5 per assay, it would take 10min to set it up,
      and only requires a small, fixed-temperature incubator. With minor modifications,
      it could be much more sensitive and easy to run and/or can provide information on
      presence of specific bacteria.

PMID- 27873601
TI  - Vancomycin in the treatment of meticillin-resistant Staphylococcus aureus (MRSA)
      infection: End of an era?
AB  - Infection with meticillin-resistant Staphylococcus aureus (MRSA) continues to
      have significant morbidity and mortality. Vancomycin, which has been the mainstay
      of treatment of invasive MRSA infections, has several drawbacks related to its
      pharmacological properties as well as varying degrees of emerging resistance.
      These resistant subpopulations are difficult to detect, making therapy with
      vancomycin less reliable. The newer agents such as linezolid, daptomycin,
      ceftaroline, and the newer glycopeptides telavancin and oritavancin are useful
      alternatives that could potentially replace vancomycin in the treatment of
      certain conditions. By summarising the discussions that took place at the III
      MRSA Consensus Conference in relation to the current place of vancomycin in
      therapy and the potential of the newer agents to replace vancomycin, this review
      focuses on the challenges faced by the laboratory and by clinicians in the
      diagnosis and treatment of MRSA infections.

PMID- 27873602
TI  - 'The Chennai declaration': India co-ordinates action against antimicrobial
      resistance.

PMID- 27873603
TI  - First National Workshop on Antibiotic Resistance in Cambodia: Phnom Penh,
      Cambodia, 16-18 November 2011.
AB  - The First National Workshop on Antibiotic Resistance in Cambodia was organised by
      the Cambodian Ministry of Health with support from several national and
      international partner institutions. It brought together policy-makers,
      clinicians, pharmacists, laboratory technicians and other professionals dealing
      with the problems of bacterial infection and antibiotic resistance across the
      country. Antibiotic resistance data from starting up and experienced laboratories
      were presented, showing high rates of resistance in key pathogens to most
      antibiotics currently available in Cambodia, e.g. 70-90% multidrug resistance and
      70-80% decreased ciprofloxacin susceptibility in Salmonella enterica serovar
      Typhi, 20-40% meticillin resistance rates in Staphylococcus aureus and 30-50%
      extended-spectrum beta-lactamase production in Escherichia coli. A five-point
      plan was discussed, which included initiatives from government and non
      governmental partners, focusing on rational prescribing, clinical practice
      guidelines, improved laboratory services, infection prevention and enhanced
      education at all levels. Implementation, however challenging, is a priority given
      the high levels of resistance seen in key pathogens and the overall health needs
      in the country.

PMID- 27873604
TI  - In vivo transmission of a plasmid containing the KPC-2 gene in a single patient.
AB  - Here we describe a case of in vivo horizontal interspecies transmission of a KPC
      2-producing plasmid from a Klebsiella pneumoniae to an Enterobacter aerogenes
      strain in the same patient. The patient's gut flora initially contained a
      carbapenem-susceptible E. aerogenes strain and 10 days after admission a KPC-2
      positive K. pneumoniae. Three months after admission, a KPC-2-positive E.
      aerogenes was identified in fecal surveillance cultures. This isolate was
      isogenic with the initial E. aerogenes and contained a KPC-2-coding plasmid
      identical to that of the K. pneumoniae. The patient developed bacteraemia by the
      KPC-2-positive K. pneumoniae 17 days after her first colonization. In vivo
      horizontal transmission of blaKPC-carrying plasmids between bacterial species
      underscores the importance of antibiotic stewardship along with implementation of
      infection control measures for the containment of KPC-producers.

PMID- 27873605
TI  - What is the evidence for the duration of antibiotic therapy in Gram-negative
      bacteraemia caused by urinary tract infection? A systematic review of the
      literature.
AB  - The frequency of secondary bacteraemia is variable depending on the site of
      infection but is often associated with significant morbidity and mortality. The
      most common source of Gram-negative bacteraemia is urinary tract infection (UTI).
      Current guidelines on the treatment of UTI provide no clear guidance on whether
      the presence of bacteraemia influences the duration or choice of therapy. Here we
      systematically review the current evidence base for the duration of treatment of
      Gram-negative bacteraemia secondary to UTI. The available evidence is sparse and
      of variable quality to draw any firm conclusions. However, in the absence of
      urgently required high-quality studies, current limited evidence appears to
      indicate that short courses of antibiotics are as effective at obtaining clinical
      and bacteriological cure as longer courses.

PMID- 27873606
TI  - Controlling hospital MRSA.
AB  - Recent evidence from publications describing the success of interventions to
      control hospital meticillin-resistant Staphylococcus aureus (MRSA), often in the
      endemic setting, is reviewed. Overall, there is cautious ground for optimism that
      MRSA can be controlled in a cost-effective manner by employing a bundle approach,
      the mainstay of which is widespread admission screening to inform patient
      specific control measures.

PMID- 27873607
TI  - Susceptibility of Gram-negative urinary tract isolates to mecillinam in a large
      Glasgow teaching hospital.

PMID- 27873608
TI  - 'The Chennai Declaration': An Indian perspective on the antimicrobial resistance
      challenge.
AB  - 'The Chennai Declaration', the consensus document of the meeting 'A Roadmap to
      Tackle the Challenge of Antimicrobial Resistance', is the first of its kind in
      Indian medical history on the subject. The Declaration is a compilation of clear
      cut and practical recommendations suitable to the Indian scenario. Sincere
      efforts to implement these recommendations will be an inspiring example to the
      whole region.

PMID- 27873610
TI  - Long-range DHPS mutations unexpectedly increase Mycobacterium chimaera
      susceptibility to sulfonamides.
AB  - The two closely related mycobacteria, Mycobacterium intracellulare and
      Mycobacterium chimaera, exhibit a more than two-fold difference in their in vitro
      susceptibility to sulfonamides. Sulfonamides are antibiotics targeting the 6
      hydroxymethyl-7,8-dihydropteroate synthase (DHPS) enzyme involved in the folate
      synthesis pathway. Comparing the DHPS gene sequence in six M. intracellulare and
      M. chimaera types trains and clinical isolates yielded only four amino acid
      changes. In silico structural modelling surprisingly indicated that these amino
      acids are not located in the active site of DHPS and do not interact directly
      with sulfonamides. Unexpectedly, these amino acids in distal positions may play a
      key role in the increased sulfonamide susceptibility observed in M. chimaera
      compared with M. intracellulare. This example illustrates how three-dimensional
      models could help to identify distal mutations capable of modulating enzymatic
      activity.

PMID- 27873609
TI  - Carbapenemases: Partners in crime.
AB  - Carbapenemases, beta-lactamases that inactivate carbapenems and most beta-lactam
      antibiotics, are most widely known for their ability to confer resistance to beta
      lactams. They include serine carbapenemases, such as the widespread KPC family of
      enzymes, and the metallo-beta-lactamases that contain the IMP, NDM and VIM enzyme
      families acquired by Gram-negative bacteria on transferable elements. These
      enzymes are almost always produced by organisms that encode at least one other
      beta-lactamase, with as many as eight different beta-lactamase genes detected in
      a single isolate. This consortium of beta-lactamases includes a full spectrum of
      molecular and biochemical characteristics, providing the producing organism with
      a range of catalytic activities. In addition to the variety of beta-lactamases
      found in carbapenemase-producing Gram-negative pathogens are multiple other
      resistance factors, especially aminoglycoside-modifying enzymes and 16S rRNA
      methylases that confer resistance to aminoglycosides. Other acquired genes encode
      fluoroquinolone, trimethoprim, sulfonamide, rifampicin and chloramphenicol
      resistance determinants on mobile elements that travel together with beta
      lactamase genes. Thus, the recent proliferation of transferable carbapenemases
      serves to magnify resistance to virtually all antibiotic classes. Judicial use of
      current antibiotics and a quest for novel antibacterial agents are necessary, as
      multidrug-resistant bacteria continue to multiply.

PMID- 27873611
TI  - Prevalence of nasal carriage and diversity of Staphylococcus aureus among
      inpatients and hospital staff at Korle Bu Teaching Hospital, Ghana.
AB  - There is a paucity of data on Staphylococcus aureus epidemiology in Africa.
      Prevalence of nasal carriage and genetic diversity of S. aureus were determined
      among hospital staff (HS) and inpatients (IP) at the largest hospital in Ghana.
      In total, 632 nasal swabs were obtained from 452 IP and 180 HS in the Child
      Health Department (CHD) and Surgical Department (SD). S. aureus carriage
      prevalences were 13.9% in IP and 23.3% in HS. The chance of being a carrier was
      higher in HS (P=0.005) and IP staying <=7 days in hospital (P=0.007). Resistance
      to penicillin (93%), tetracycline (28%) and fusidic acid (12%) was more common
      than for other agents (<5%). A higher chance of multidrug-resistant S. aureus
      carriage was observed among IP compared with HS (P=0.01). High genetic diversity
      was shown by spa typing, with 55 spa types found among 105 isolates; the
      predominant spa types were t355 (10%) and t084 (10%). MRSA was detected in six IP
      with an overall carriage prevalence of ca. 1.3%, but not in HS. All three MRSA
      isolates from SD belonged to ST88-SCCmec IV, and two of them displayed the same
      spa type and antibiograms; three MRSA isolates from CHD belonged to distinct
      lineages (ST88-SCCmec IV, ST8-SCCmec V and ST72-SCCmec V). Altogether, these data
      indicate a high diversity of S. aureus, low levels of MRSA carriage, and a higher
      chance of nasal carriage of multidrug-resistant S. aureus among IP compared with
      HS in this hospital.

PMID- 27873612
TI  - Activity of the antiseptic polyhexanide against meticillin-susceptible and
      meticillin-resistant Staphylococcus aureus.
AB  - Staphylococcus aureus is one of the most important pathogens, with increasing
      emergence of meticillin-resistant S. aureus (MRSA) strains. This is associated
      not only with multiresistance to antibiotics but also with increasing resistance
      to topical antibiotics and antiseptics. As the antiseptic polyhexanide has only a
      low risk of emergence of resistant strains, the aim of the study was to obtain
      data on the sensitivity of S. aureus towards polyhexanide. The effect of
      polyhexanide was tested against 80 meticillin-susceptible S. aureus (MSSA) and 80
      MRSA strains from sporadic cases as well as against 6 MRSA outbreak strains. The
      clonal diversity of the 166 strains was proven by pulsed-field gel
      electrophoresis (PFGE). Minimum inhibitory concentrations (MICs) and minimum
      bactericidal concentrations (MBCs) were determined by the serial broth
      microdilution technique according to DIN 58940. Time-kill studies were performed
      for reference strains MSSA ATCC 29213 and MRSA ATCC 33591. MICs and MBCs in the
      range of 0.5-2mg/L were found. According to a created epidemiological cut-off
      (ECOFF) value of 4mg/L, all strains were regarded as susceptible to polyhexanide,
      including MRSA epidemic strains and MSSA and MRSA sporadic strains with various
      antibiotic susceptibility patterns. Addition of up to 4% albumin to the test
      medium did not change the MICs and MBCs. Time-kill studies showed reduction rates
      of 4log10CFU/mL for 200mg/L and 5log10CFU/mL for 400mg/L polyhexanide within 5
      30min. It is concluded that polyhexanide is suitable for topical eradication of
      S. aureus.

PMID- 27873613
TI  - Decreasing trends of drug resistance and increase of non-B subtypes amongst
      subjects recently diagnosed as HIV-infected over the period 2004-2012 in the
      Veneto Region, Italy.
AB  - The present study was designed to prospectively monitor transmitted drug
      resistance mutations (TDRMs) in the Veneto Region, Italy. Genotypic resistance
      testing was conducted on the plasma of 1882 patients consecutively enrolled at
      the time of diagnosis of human immunodeficiency virus (HIV) infection from 2004
      to 2012. TDRMs were defined according to the Stanford HIV database algorithm. In
      total, 214 (16.1%) B subtype-infected and 58 (10.5%) non-B subtype-infected
      individuals were identified as having a primary or recent HIV-1 infection. In
      subtype B-infected subjects in 2004-2006, the prevalence of TDRMs was 20.0% in
      chronic infections and 25.5% in recent infections; in 2007-2009 the rates were
      11.5% and 5.3%, respectively; and in 2010-2012 they were 11.3% and 15.2%,
      respectively. In non-B subtype-infected subjects in 2004-2006, the prevalence of
      TDRMs was 18.0% in chronic infections and 16.5% in recent infections; in 2007
      2009 the rates were 5.7% and 0%, respectively; and in 2010-2012 they were 6.2%
      and 8.7%, respectively. Protease inhibitor resistance and combined resistance to
      two or three classes of drugs declined during the three study periods. The
      observed decrease in TDRMs and a simplification of the resistance patterns may
      reflect a change over time in the characteristics of the infecting subjects who
      are often unaware of their infection and transmit a wild-type strain.

PMID- 27873614
TI  - Polymicrobial bloodstream infections: Epidemiology and impact on mortality.
AB  - The aim of this study was to investigate the impact of polymicrobial bloodstream
      infections (pBSIs) on the outcome of sepsis in an area where antimicrobial
      resistance is of concern. This was a retrospective analysis of data collected
      prospectively from patients developing BSI outside of an intensive care unit (non
      ICU patients) or after ICU admission. Demographics and clinical characteristics
      were compared for patients with pBSI versus monomicrobial BSI (mBSI) and
      following stratification by ICU or non-ICU and severity of sepsis status.
      Possible risk factors for adverse outcome were explored by multivariate analysis,
      and outcomes were measured by Cox regression analysis. Among 412 patients with
      BSI, 47 patients (11.4%) with pBSI were recorded; compared with patients with
      mBSI, they had significantly higher APACHE II scores and presented more
      frequently with severe sepsis/septic shock. The all-cause 28-day mortality was
      significantly higher for pBSI versus mBSI (38.3% vs. 24.7%; P=0.033), whereas
      appropriateness of treatment was comparable (78.7% vs. 86.6%). Primary
      bacteraemia by combinations of Enterococcus faecalis, Klebsiella pneumoniae and
      Acinetobacter baumannii was predominant among pBSIs; in mBSIs, urinary tract
      infections by Escherichia coli, K. pneumoniae or Pseudomonas aeruginosa
      predominated. Multivariate analysis demonstrated pBSI as a significant
      contributor to 28-day mortality (HR=1.86; P=0.039), along with presence of two or
      more co-morbidities (HR=2.35; P=0.004). In conclusion, pBSIs differed
      epidemiologically from mBSIs, with the emergence of enterococcal species, and
      portended an almost two-fold increased risk of 28-day mortality. Prospective
      studies are warranted to elucidate possibly modifiable factors.

PMID- 27873615
TI  - NDM-1- and OXA-163-producing Klebsiella pneumoniae isolates in Cairo, Egypt,
      2012.
AB  - Here we describe carbapenem resistance determinants in two Klebsiella pneumoniae
      isolates recovered from two hospitalised patients in the same intensive care unit
      of a cancer hospital in Cairo, Egypt. PCR and sequencing were used to detect and
      characterise beta-lactamase genes. Clonal relationships between the isolates were
      analysed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence
      typing (MLST). The first K. pneumoniae isolate carried the blaNDM-1 gene and the
      second isolate carried the blaOXA-163 gene. Both isolates co-expressed the
      extended-spectrum beta-lactamase CTX-M-15. The two isolates belonged to different
      sequence types (STs), ST11 and ST16, respectively. No history of travel was
      established for the two patients. The first identification of NDM-1-producing K.
      pneumoniae in Egypt adds further evidence to the spread of NDM-1-producing Gram
      negative micro-organisms in North Africa. The additional detection of blaOXA-163
      in a K. pneumoniae isolate confirms its endemic presence in a critical healthcare
      setting of this geographic area.

PMID- 27873616
TI  - Emergence of blaKPC-3-Tn4401a in Klebsiella pneumoniae ST512 in the municipal
      wastewater treatment plant and in the university hospital of a town in central
      Italy.
AB  - In this study, 20 carbapenem-resistant environmental Klebsiella pneumoniae
      strains were found to correlate with 18 clinical K. pneumoniae isolates from the
      teaching hospital of L'Aquila city, Italy. All strains analysed by multilocus
      sequence typing (MLST) were included in the same clone (ST512), and pulsed-field
      gel electrophoresis demonstrated a genetic relationship between the clinical
      isolates and most environmental strains. Both environmental and clinical strains
      harboured the same mobile genetic elements: transposon Tn4401a including a blaKPC
      3 determinant; and a class 1 integron with the gene cassette aadA2.

PMID- 27873617
TI  - Can ampicillin/sulbactam resistance in Acinetobacter baumannii be predicted
      accurately by disk diffusion?
AB  - The objective of this study was to compare the performance of disk diffusion and
      agar dilution for the determination of susceptibility to ampicillin/sulbactam
      (SAM), ceftazidime, cefepime, imipenem, meropenem, polymyxin B and tigecycline of
      121 Acinetobacter baumannii clinical isolates. The antimicrobial susceptibility
      testing methods were performed as recommended by the Clinical and Laboratory
      Standards Institute (CLSI). For SAM, in addition the Etest method was performed
      according to the manufacturer's instructions. The error rates for the
      antimicrobial agents for 121 isolates tested were within the acceptable ranges
      established by the CLSI, with the exception of SAM and polymyxin B. For polymyxin
      B, there were 1.7% very major errors and for SAM there were 15% comparing disk
      diffusion with agar dilution. The very major error rate of SAM comparing the
      Etest with agar dilution was 10%. These high observed rates of very major error
      cast doubt on the disk diffusion and Etest techniques as appropriate methods for
      detecting resistance to SAM.

PMID- 27873618
TI  - Hospital-associated meticillin-resistant Staphylococcus pseudintermedius in a
      French veterinary hospital.

PMID- 27873619
TI  - Carbapenem-hydrolysing beta-lactamase KPC-2 in Klebsiella pneumoniae isolated in
      Ecuadorian hospitals.

PMID- 27873620
TI  - Emergence of quinolone resistance in Salmonella and Shigella strains isolated
      from diarrhoea in Senegal.

PMID- 27873621
TI  - Treatment of extensively drug-resistant Gram-negative infections in critically
      ill patients: Outcome of a consensus meeting at the 13th Asia-Pacific Congress of
      Clinical Microbiology and Infection, October 2012.
AB  - Infections caused by multidrug-resistant and extensively drug-resistant Gram
      negative bacilli are increasingly challenging to manage in hospitals and long
      term-care facilities worldwide. As the therapeutic options are limited, the
      International Society of Chemotherapy in collaboration with the Asia-Pacific
      Society of Clinical Microbiology and Immunology organised a consensus conference
      as part of the 13th Asia-Pacific Congress of Clinical Microbiology and Infection.
      A panel of international experts from Europe, the Americas and Asia were convened
      to discuss the issues of therapeutic options for the management of these
      difficult-to-treat pathogens.

PMID- 27873622
TI  - Inappropriate empirical antimicrobial therapy for multidrug-resistant organisms
      in critically ill patients with pneumonia is not an independent risk factor for
      mortality: Results of a prospective observational study of 758 patients.
AB  - The benefits of broad-spectrum initial empirical antibiotic therapy for all
      patients in intensive care units (ICUs) with high rates of multidrug-resistant
      organisms (MDROs) have not been critically evaluated. In this study, 758 ICU
      patients with pneumonia were prospectively evaluated. Of 349 positive respiratory
      cultures, 119 (34.1%) were with MDRO isolates. These were associated with
      increased mortality [adjusted hazard ratio (HR)=1.65, 95% confidence interval
      (CI) 1.01-2.68; P=0.04] as was increasing age and Acute Physiology and Chronic
      Health Evaluation (APACHE) II score. Among the patients with MDRO-associated
      pneumonia, increasing age, APACHE II score and inappropriate definitive
      antimicrobial therapy (IDAT) were found to be significant risk factors for
      mortality (in-ICU mortality, adjusted HR=2.8, 95% CI 1.3-5.8; P=0.007), but
      inappropriate empirical antimicrobial therapy (IEAT) was not (in-ICU mortality,
      unadjusted HR=1.6, 95% CI 0.7-3.6; P=0.3). In conclusion, we found that among
      critically ill patients with MDRO-associated pneumonia, IEAT is not an
      independent risk factor for ICU mortality. Hence, we do not recommend the use of
      broad-spectrum initial empirical antimicrobial therapy for all patients, as its
      benefits may not outweigh the potential risks. Early microbiological diagnosis to
      facilitate implementation of early definitive antimicrobial therapy through use
      of novel technologies is likely to have a major impact.

PMID- 27873623
TI  - Emerging and existing mechanisms co-operate in generating diverse beta-lactam
      resistance phenotypes in geographically dispersed and genetically disparate
      Pseudomonas aeruginosa strains.
AB  - beta-Lactam resistance in Pseudomonas aeruginosa clinical isolates is driven by a
      number of mechanisms. Whilst several are understood, how they act co-operatively
      in pathogenic strains is less clear. In some isolates, resistance profiles cannot
      always be explained by identifying the common resistance-determining pathways,
      suggesting that other mechanisms may be important. Pathogenic P. aeruginosa
      isolates from four countries were characterised by PCR. Quantitative expression
      analysis was also assessed for the activity of several pathways that influence
      antibiotic resistance, and culture experiments were conducted to test how random
      transposition of the insertion sequence IS26 during growth may influence
      resistance to some antibiotics. In most strains, antibiotic resistance was being
      driven by changes in multiple pathways and by the presence or absence of genes
      acquired by lateral gene transfer. Multiple mechanisms of resistance were
      prevalent in strains from all of the countries examined, although regional
      differences in the type of interacting mechanisms were apparent. Changes in
      chromosomal pathways included overexpression of AmpC and two efflux pumps. Also,
      gain or loss of IS26 at some chromosomal locations, most notably oprD, could
      influence resistance to carbapenems. IS26-related resistance was found in strains
      from Argentina and geographically linked Uruguay, but not in strains from either
      Colombia or Australia. Pseudomonas aeruginosa pathogenic strains are evolving to
      become multidrug-resistant in more complex ways. This is being influenced by
      single strains acquiring changes in numerous known pathways as well as by newly
      emerging resistance mechanisms in this species.

PMID- 27873625
TI  - Antimicrobial susceptibility of Staphylococcus aureus and molecular epidemiology
      of meticillin-resistant S. aureus isolated from Australian hospital inpatients:
      Report from the Australian Group on Antimicrobial Resistance 2011 Staphylococcus
      aureus Surveillance Programme.
AB  - The Australian Group on Antimicrobial Resistance (AGAR) performs regular
      multicentre period prevalence studies to monitor changes in antimicrobial
      resistance. In 2011, 29 laboratories in Australia participated in the national
      surveillance of Staphylococcus aureus resistance. The survey only included unique
      isolates from clinical specimens collected >=48h after hospital admission. MRSA
      accounted for 30.3% of S. aureus isolates. MRSA resistance to ciprofloxacin,
      erythromycin, tetracycline, trimethoprim/sulfamethoxazole, gentamicin and
      clindamycin (constitutive resistance) varied considerably between regions.
      Resistance to non-beta-lactam antimicrobials was uncommon in MSSA, with the
      exception of erythromycin. Regional variation in resistance was due to the
      differential distribution of MRSA clones between regions. The proportion of S.
      aureus genetically characterised as healthcare-associated MRSA (HA-MRSA) was
      significantly lower in this survey (18.2%) compared with the 2005 survey (24.2%)
      (P<0.0001). Although four HA-MRSA clones were characterised, 98.8% of HA-MRSA
      were classified as either ST22-MRSA-IV [2B] (EMRSA-15) or ST239-MRSA-III [3A]
      (Aus-2/3 EMRSA). Multiclonal community-associated MRSA (CA-MRSA) increased
      markedly from 6.5% in 2005 to 11.7% of all S. aureus in 2011 (P<0.0001). Although
      the proportion of MRSA resistant to non-beta-lactam antimicrobials has decreased
      nationally, the proportion of S. aureus that are MRSA has remained stable. This
      is primarily due to non-multiresistant CA-MRSA becoming more common in Australian
      hospitals at the expense of the long-established multiresistant ST239-MRSA-III
      [3A] (Aus-2/3 EMRSA). Given hospital outbreaks of CA-MRSA are thought to be
      extremely rare, it is most likely that patients colonised at admission with CA
      MRSA have become infected with the colonising strain during their hospital stay.

PMID- 27873624
TI  - Identification of the first blaCMY-2 gene in Salmonella enterica serovar
      Typhimurium isolates obtained from cases of paediatric diarrhoea illness detected
      in South America.
AB  - The objectives of this study were to investigate clinical isolates of Salmonella
      enterica serovar Typhimurium resistant to beta-lactam antibiotics, to
      characterise their mechanisms of antibiotic resistance and to evaluate the
      possible biological cost of expressing resistance genes. Two oxyimino
      cephalosporin-resistant Salmonella isolates obtained from children with diarrhoea
      were characterised. The occurrence of plasmid-encoded blaCMY-2 genes was
      confirmed by molecular methods and conjugation assays; transcription levels were
      determined by quantitative real-time PCR (qRT-PCR). The genomic context of the
      beta-lactamases, replicon type and addiction systems were analysed by PCR.
      Genomic relatedness of both isolates was studied by pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST) assays. Growth
      curves, motility and invasiveness assays in Caco-2 cells were performed to
      analyse the bacterial fitness of both isolates. Both isolates carried a blaCMY-2
      like allele in an IncI plasmid and belonged to the same MLST sequence type
      (ST19); nevertheless, they showed extensive differences in their PFGE profiles
      and virulotypes. Isolate STM709 appeared to lack the Salmonella virulence plasmid
      and displayed less motility and invasiveness in cultured cells than isolate
      STM910. qRT-PCR showed that isolate STM709 had higher blaCMY-2 mRNA levels
      compared with STM910. Altogether, the results suggest that a plasmid carrying
      blaCMY-2 could be disseminating among different clones of S. Typhimurium.
      Different levels of blaCMY-2 mRNA could have an effect on the fitness of this
      micro-organism, resulting in lower invasiveness and motility.

PMID- 27873626
TI  - Salmonella prevalence in meat at retail markets in Pakse, Champasak Province,
      Laos, and antimicrobial susceptibility of isolates.
AB  - Non-typhoidal Salmonella is one of the most common causes of human
      gastroenteritis worldwide and most human outbreaks are associated with the
      consumption of contaminated food. However, there are no reports on Salmonella
      contamination in market meat in Laos. The objective of this study was to
      determine the prevalence of Salmonella in meat samples in Pakse, Champasak
      Province, Laos, as well as the antimicrobial susceptibility of isolates. The
      prevalence of Salmonella was 82% in beef, 93% in pork and 80% in buffalo meat. In
      total, 80 isolates and 11 serovars were found, including serovars Stanley (n=15),
      Anatum (n=14), Derby (n=11), Rissen (n=9) and Amsterdam (n=7). The drug
      susceptibility of 60 strains against 10 antimicrobial agents was tested. The 60
      isolates examined were sensitive to ciprofloxacin (100% susceptible), norfloxacin
      (100%), cefotaxime (95%), nalidixic acid (90%) and chloramphenicol (88%), but
      were resistant to streptomycin (67% resistant), tetracycline (67%) and ampicillin
      (63%). Of the isolates, 73% were multidrug-resistant. These findings indicate a
      high Salmonella prevalence in market meat in Pakse. Therefore, programmes to
      control Salmonella contamination are needed.

PMID- 27873627
TI  - Performance of different commercial methods for determining minimum inhibitory
      concentrations of glycopeptides and linezolid against blood isolates of
      Staphylococcus aureus.
AB  - The aim of this study was to determine the accuracy of commercial systems
      (VITEK(r) 2, Etest and Sensititre(r)) in determining the minimum inhibitory
      concentrations of vancomycin, teicoplanin and linezolid of Staphylococcus aureus
      strains and to evaluate the reproducibility of each system in a clinical
      microbiology laboratory. In total, 115 strains of S. aureus isolated from blood
      cultures were tested with all three commercial methods as well as the broth
      microdilution method, which is designated as the standard for glycopeptides and
      linezolid. Fourteen different S. aureus strains were included in a
      reproducibility test for all methods and antibiotics. For these strains,
      antimicrobial susceptibility testing was repeated 10 times on different days with
      all four methods, each time using the same inoculum. All three commercial methods
      exhibited similar performance in categorisation of nearly all of the meticillin
      susceptible S. aureus (MSSA) isolates. Discrepancies were registered for
      meticillin-resistant S. aureus (MRSA); 2.5% of the strains in the intermediate or
      resistant category with the VITEK 2 system were not recognised as resistant by
      Etest and Sensititre. Moreover, none of the three commercial methods provided
      accurate results compared with homemade broth microdilution. Reproducibility of
      vancomycin and teicoplanin was 100% with VITEK 2 and Sensititre and 98.75% with
      Etest. Microdilution showed a reproducibility of 95.6% with vancomycin and 83.1%
      with teicoplanin. In contrast to previous reports, the best agreement with
      microdilution was exhibited by VITEK 2 both for MSSA and MRSA. For the
      antibiotics tested, the best reproducibility was obtained with the VITEK 2 and
      Sensititre systems.

PMID- 27873629
TI  - Antimicrobial stewardship programmes in Emilia-Romagna, Italy.
AB  - The purpose of this study was to evaluate the state-of-the-art of antimicrobial
      stewardship programmes (ASPs) in Emilia-Romagna, Italy. A self-compiled, 23
      question, multiple-choice questionnaire, divided into eight sections, focusing on
      Public Health Trust (PHT) characteristics, multidisciplinary team, formulary
      restrictions, education, guidelines and protocols, auditing, antimicrobial
      therapy management and consumption, and resistance surveillance, was sent to all
      17 PHTs of Emilia-Romagna. The 'composite index of good antibiotic use' (ICATB)
      score, a French ASP process index based upon 12 different parameters, was
      calculated. All PHTs completed the survey. All PHTs had an antimicrobial control
      programme, although an antimicrobial stewardship team was present in 11/17 (65%)
      of trusts. The main results were (a) active antimicrobial committee, 47% of PHTs;
      (b) restricted formularies, 100%; (c) courses on surgical antimicrobial
      prophylaxis (SAP) and antimicrobial therapy, 56% of surgical specialties and 47%
      of PHTs, respectively; courses for new prescribers, nil; (d) guidelines on SAP
      and on antimicrobial therapy, 100% and 71% of PHTs, respectively; (e)
      antimicrobial prescribing audits, 71%; and (f) antibiotic consumption and
      antimicrobial resistance data periodically fed back to wards, 100% and 88% of
      PHTs, respectively. Low overall quality scores were observed for antibiotic
      committee, education and auditing activities. The mean ICATB score was 11.94
      points, varying significantly among trusts (5.25-16.25 points). In conclusion,
      all PHTs have implemented an ASP, although significant differences exist between
      trusts. Antimicrobial committee organisation, education and auditing activities
      represent the most critical points and need to be addressed by regional
      programmes in order to harmonise the healthcare system.

PMID- 27873630
TI  - Antimicrobial stewardship in hospitals: Does it work and can we do it?
AB  - Selection of resistant pathogens by antimicrobial use is probably the most
      important cause of antimicrobial resistance. Antimicrobial stewardship (AMS)
      refers to a multifaceted approach to optimise prescribing. The benefits of AMS
      programmes have been widely demonstrated in terms of reductions in antimicrobial
      use, mortality, Clostridium difficile and other healthcare-associated infections,
      hospital length of stay and bacterial resistance. Several kinds of interventions
      (i.e. restriction of drugs, pre-authorisation of certain antimicrobials, joint
      clinical rounds with prescribers, implementation of guidelines and education)
      have shown positive results. Regrettably, in most hospitals in Latin America,
      Asia and Africa as well as in a significant proportion of institutions in Europe
      and North America, essential human and material resources are scarce or absent,
      and teams are neither developed nor well functioning. Despite current or
      potential barriers, we should start or improve our already ongoing initiatives on
      AMS by considering the main specific problems and act accordingly with the
      available human and material resources. From supervising the use of specific
      classes of drugs to implementing more sophisticated decision support programmes,
      there is a wide range of possible useful interventions.

PMID- 27873628
TI  - The effect of chlortetracycline on faecal microbial populations in growing swine.
AB  - The effect of antimicrobial use on the gastrointestinal microbiota of food
      animals is of increasing concern as bacteria accumulate resistance to multiple
      antimicrobials. Only a small fraction of the gastrointestinal microbiome is
      culturable, complicating characterisation of the swine gastrointestinal
      ecosystem. The objective of this study was to determine the effect of a growth
      promotion dose (50g/ton) of chlortetracycline on the phylogenetic diversity of
      bacteria from swine faeces using a culture-independent method. Four freshly
      weaned pigs were provided a grower ration of primarily corn (63.7%) and soybean
      meal (25.2%) for 21 days; on Day 21 for 4 weeks the diet of two pigs was
      medicated with 50g/ton chlortetracycline. Faecal material was collected from each
      pig on Days 0, 14, 23, 28, 35, 42 and 49 for 454-pyrosequencing of the 16S rRNA
      gene. UniFrac analysis of pyrosequencing data showed no significant difference in
      bacterial diversity based on diet and among pigs (P>0.05) fed the low-level dose
      of chlortetracycline. The most abundant phyla in both treatment groups were
      Firmicutes, Bacteroidetes, Proteobacteria and Spirochaetes. Higher concentrations
      of chlortetracycline (e.g. 200g/ton or 400g/ton) may be required to observe a
      shift in the gastrointestinal flora in swine faeces compared with the low-level
      dose in this study. Studies of broader scope are needed to understand thoroughly
      how growth-promoting antimicrobials influence the gut microflora and benefit food
      animal growth efficiency.

PMID- 27873631
TI  - Action Plan to combat infections due to carbapenem-resistant, Gram-negative
      pathogens in acute-care hospitals in Greece.
AB  - The prevalence of carbapenem-resistant pathogens (CRPs) has increased worldwide.
      Given the importance of CRPs for public health and the high rates of carbapenem
      resistance observed in Greece, the Hellenic Center for Disease Control and
      Prevention (HCDCP) under the auspices of the Ministry of Health has undertaken
      initiatives to develop an Action Plan (i) to estimate the burden of CRP
      infections in acute-care hospitals in Greece and (ii) to implement infection
      control measures to limit the intrahospital transmission of these organisms.
      Starting in November 2010, specific infections caused by CRPs were reported to
      the HCDCP weekly. Results showed that CRP infections constitute a significant
      public health problem in acute-care hospitals in this country, with a mean
      incidence of 0.48 per 1000 patient-days and a crude 28-day mortality rate of
      34.4%. The second phase of the Action Plan consists of systemic evaluation for
      adherence to an infection control bundle including enhanced standard infection
      control practices, separation of carriers and infected patients from non
      carriers, and strict implementation of contact precautions. Communication between
      hospitals and public health authorities has been established to facilitate rapid
      notification and feedback.

PMID- 27873632
TI  - Distribution of beta-lactamases in carbapenem-non-susceptible Acinetobacter
      baumannii in Riyadh, Saudi Arabia.
AB  - In this study, the distribution of beta-lactamase genes among 55 consecutive
      Acinetobacter baumannii isolates with reduced susceptibility to imipenem
      collected at Prince Salman Hospital (Riyadh, Saudi Arabia) from February-June
      2011 was investigated. Minimum inhibitory concentrations (MICs) were determined
      by Etest and were interpreted against Clinical and Laboratory Standards Institute
      (CLSI) breakpoints. PCR was used to search for beta-lactamase genes, insertion
      sequence ISAba1 and class 1 integrons. Imipenem MICs ranged from 2MUg/mL to
      >=32MUg/mL and resistance to aztreonam, cefepime and ceftazidime was widespread,
      with MIC90 values (MIC required to inhibit 90% of the isolates) of >256MUg/mL.
      blaTEM, blaADC and blaOXA-51-like genes were universal, whilst blaOXA-23, blaPER,
      blaGES and blaOXA-24 were found in 60.0%, 49.1%, 34.5% and 3.6% of isolates,
      respectively. Genes for SHV, CTX-M, VEB, KPC, OXA-58 and metallo-beta-lactamases
      (MBLs) were not detected. ISAba1 was universal and consistently present upstream
      of blaOXA-51, blaOXA-23, blaOXA-24 and blaADC; class 1 integrons also were
      universal. Notably, 28/55 isolates had both an extended-spectrum beta-lactamase
      (ESBLs) and an acquired blaOXA-23 gene. High-level carbapenem resistance
      (MIC>=32MUg/mL) was consistently associated with blaOXA-23 or blaOXA-24, whereas
      low-level resistance (MIC of 2-8MUg/mL) was associated with the presence of ESBLs
      of GES or PER type and/or ISAba1-upregulated blaOXA-51-like. In conclusion,
      blaTEM, blaOXA-23, blaPER and blaGES-like genes were prevalent, often in
      combination. MBLs remained absent and high-level carbapenem resistance
      consistently correlated with the presence of blaOXA-23 or blaOXA-24.

PMID- 27873633
TI  - Impact of clinical syndrome-wise categorisation of antimicrobial susceptibility
      profiles on nosocomial isolates in a tertiary care hospital in Delhi, India.
AB  - The objective of this study was to investigate the impact of clinical syndrome
      wise categorisation of antimicrobials on the antibiotic susceptibility of
      nosocomial bacteria at a tertiary care hospital in Delhi, India. The
      susceptibility of 226 nosocomial bacterial isolates collected during 2008-2011 to
      meropenem, piperacillin/tazobactam, cefepime, tigecycline, amoxicillin/clavulanic
      acid (AMC), amikacin, ceftriaxone and ciprofloxacin was monitored and was
      compared with the antibiotic susceptibility profiles of 72 isolates collected
      during 2002-2007. During 2008-2011, the isolates included 85% Gram-negative
      isolates and 15% meticillin-sensitive staphylococci. There was no difference in
      the susceptibility of the isolates between 2002 and 2007 and 2008-2011, except
      for a significant increase in Escherichia coli isolates susceptible to AMC (from
      73% to 100%), amikacin (70-100%) and cefepime (22-86%), in Klebsiella isolates
      susceptible to ciprofloxacin (from 25% to 80%) and cefepime (45-75%) and in
      Pseudomonas isolates susceptible to AMC (from 25% to 86%). In conclusion, during
      the past decade a clinical syndrome-wise categorisation of antimicrobials in
      frequent usage as well as culture-based categorisation of infections into
      nosocomial/community-acquired was useful in establishing the generally
      insignificant change in the susceptibility of nosocomial isolates and an upsurge
      in the susceptibility of some isolates to a few antimicrobials. Regular updates
      on drifts in the antimicrobial susceptibility of local isolates and surveillance
      of nosocomial infections would be valuable for tackling the emergence of
      antibiotic-resistant bacteria.

PMID- 27873634
TI  - Risk factors for community-associated methicillin-resistant Staphylococcus aureus
      colonisation in a large metropolitan area in Greece: An epidemiological study
      using two case definitions.
AB  - The aim of this study was to evaluate the epidemiology and characteristics and to
      identify modifiable risk factors for community-associated (CA) MRSA colonisation
      in a region with high prevalence. A large patient population (n=2280) from two
      tertiary care centres in Athens (Greece) was evaluated. Demographics and
      potential risk factors for CA-MRSA colonisation were recorded prospectively.
      Presence of the Panton-Valentine Leukocidin (PVL) toxin and mecA gene was
      determined in all MRSA isolates. Two definitions for CA-MRSA were applied.
      Univariate and multivariate analyses to identify predictors of previously unknown
      CA-MRSA colonisation were performed. In total, 120 (5.3%) MRSA carriers were
      identified; in 67 the isolates were classified as CA-MRSA using criteria based on
      the CDC definition, compared with 35 based on a definition including PVL toxin
      positivity. Factors significantly associated with previously unknown CA-MRSA
      carriage (CDC definition) included being a child or adolescent (OR=3.6, 95% CI
      1.5-8.6), belonging to the family of an index case (OR=2.4, 95% CI 1.2-4.8), and
      presence of any co-morbidity (OR=1.7, 95% CI 1.04-2.8) or chronic skin disease
      (OR=3.6, 95% CI=2.2-6.1). In multivariate analysis, presence of any co-morbidity
      was the only significant predictor (OR=4.9, 95% CI 1.07-22.5; P=0.04). No easily
      modifiable risk factor for previously unknown CA-MRSA colonisation was
      identified. The CDC-based epidemiological definition for CA-MRSA appears to be
      more sensitive in detection of CA-MRSA colonisation than a purely molecular
      definition based on presence of the PVL gene.

PMID- 27873635
TI  - Susceptibility profiles of Propionibacterium acnes isolated from patients with
      acne vulgaris.
AB  - The wide prescription of antibiotics in patients with acne vulgaris has generated
      the concern of emergence of antibiotic-resistant Propionibacterium acnes. To
      study the susceptibility profiles of P. acnes isolated from patients with acne
      vulgaris, 90 isolates were isolated from sebum collected from lesions of 191
      patients. Susceptibilities to amoxicillin, minocycline, erythromycin and
      clindamycin were studied by the Etest method. Thirty-four isolates (37.8%) were
      resistant to both erythromycin and clindamycin, whereas another four isolates
      (4.4%) were resistant to all four tested antimicrobials. All resistant isolates
      to any of the tested antimicrobials had very high minimum inhibitory
      concentrations (>256MUg/mL). Among all analysed host factors, only history of
      oral treatment with macrolides and/or clindamycin within the last 2 years was
      independently associated with the acquisition of resistant P. acnes (odds
      ratio=5.573; P=0.001). The present results provide useful information to guide
      antimicrobial prescribing strategies in acne. Any information for past exposure
      to macrolides or clindamycin should suggest avoidance of prescription of these
      antibiotics. Tetracyclines and amoxicillin are the suggested solutions for these
      patients. In contrast, lack of history of exposure allows the safe prescription
      of macrolides and clindamycin.

PMID- 27873636
TI  - A pilot study of risk adjustment for benchmarking antibiotic use between
      hospitals in Sweden.
AB  - There is no established standard for comparing overall antibiotic use between
      hospitals taking patient characteristics into account. The objective of this
      study was to investigate whether there is a correlation between surrogate markers
      for patient morbidity, namely case mix index (CMI), mean length of hospital stay
      (LoS) and mean cost per admission, and antibiotic use in a sample of Swedish
      hospitals. All primary and secondary hospitals in three counties with high and
      three counties with low consumption of antibiotics were selected. Data from 16
      hospitals were included. A regression analysis was used to evaluate whether there
      was a linear trend between defined daily doses (DDD) of antibiotics per 100 bed
      days and the surrogate markers for morbidity. No correlation could be found
      between any of the measures of morbidity and total antibiotic consumption.
      However, a correlation was found between CMI and the proportion of narrow
      spectrum antibiotics: the higher the CMI, the lower the proportional use of beta
      lactamase-sensitive penicillins. In conclusion, it was found that CMI, mean LoS
      and mean cost per admission did not appears to be useful factors to adjust for
      when comparing antibiotic use in this subset of primary and secondary care
      hospitals. Based on this limited study, we suggest that DDD/100 bed-days can
      still be used as an appropriate metric to benchmark antibiotic use in primary and
      secondary hospitals until a better marker for variation of patients and
      activities is identified.

PMID- 27873638
TI  - Prevalence of in vitro susceptibility to carbapenems among clinical isolates of
      the Bacteroides fragilis group from a Colombian tertiary hospital.
AB  - Clinical isolates of the Bacteroides fragilis group (n=29) were collected from
      patients attending a tertiary care hospital in Medellin, Colombia, during 2012
      and were tested for susceptibility to four carbapenems using the Clinical and
      Laboratory Standards Institute (CLSI) Etest method. Overall rates of percent
      susceptibility were as follows: meropenem, 93.1%; imipenem, 100%; ertapenem,
      96.6%; and doripenem, 93.1%. This is the first study to show rates of resistance
      of Bacteroides spp. to carbapenems in Colombia among a species formerly thought
      to be fully susceptible to this type of antimicrobial.

PMID- 27873639
TI  - Changing molecular epidemiology and high rates of mupirocin resistance among
      meticillin-resistant Staphylococcus aureus in Singaporean hospitals.
AB  - A prospective cross-sectional study was performed to determine the continuing
      shift in the molecular epidemiology of meticillin-resistant Staphylococcus aureus
      (MRSA) in Singapore. In total, 666 MRSA isolates from screening cultures
      performed between 7 and 20 January 2013 were obtained from all seven public
      sector hospitals in Singapore and were subjected to molecular typing using
      multilocus variable-number tandem-repeat fingerprinting with confirmatory
      multilocus sequencing typing for clustered isolates. Isolates were also tested
      for the presence of the orfX-ACME insert and the high-level mupirocin resistance
      gene ileS-2. The major circulating clones in Singaporean hospitals were ST22
      (63.2%), ST45 (18.9%) and ST239 (10.7%). The orfX-ACME insert was only found in
      ST239 isolates (31/71, 43.7%), but ileS-2 was found in 207 (31.1%) of the MRSA
      isolates, varying between 10.0% and 47.8% among the hospitals. In conclusion, the
      molecular epidemiology of MRSA in Singaporean hospitals has continued to change,
      with ST45 now replacing ST239 in addition to the ongoing replacement of the
      latter by ST22. Although a greater proportion of ST239 isolates carry the orfX
      ACME insert, the actual clinical impact may be marginal as ST239 MRSA continues
      to decline. Finally, high-level mupirocin resistance rates are remarkably high in
      local healthcare-associated MRSA, with implications for MRSA decolonisation and
      infection prevention. Further surveillance is required to monitor the changing
      epidemiological trends.

PMID- 27873637
TI  - Antibiotic susceptibility and molecular epidemiology of Panton-Valentine
      leukocidin-positive meticillin-resistant Staphylococcus aureus: An international
      survey.
AB  - The antibiotic susceptibility and molecular epidemiology of Panton-Valentine
      leukocidin (PVL)-positive meticillin-resistant Staphylococcus aureus (MRSA)
      isolates reported from 17 countries in the Americas, Europe and, Australia-Asia
      were analysed. Among a total of 3236 non-duplicate isolates, the lowest
      susceptibility was observed to erythromycin in all regions. Susceptibility to
      ciprofloxacin showed large variation (25%, 75% and 84% in the Americas, Europe
      and Australia-Asia, respectively). Two vancomycin-intermediate PVL-positive MRSA
      isolates were reported, one from Hong Kong and the other from The Netherlands.
      Resistance to trimethoprim/sulfamethoxazole and linezolid was <1%. Among 1798
      MRSA isolates from 13 countries that were tested for the requested 10 non-beta
      lactam antibiotics, 49.4% were multisusceptible. However, multiresistant isolates
      (resistant to at least three classes of non-beta-lactam antibiotics) were
      reported from all regions. Sequence type 30 (ST30) was reported worldwide,
      whereas ST80 and ST93 were exclusive to Europe and Australia, respectively.
      USA300 and related clones (ST8) are progressively replacing the ST80 clone in
      several European countries. Eight major clusters were discriminated by multilocus
      variable-number tandem repeat assay (MLVA), showing a certain geographic
      specificity. PVL-positive MRSA isolates frequently remain multisusceptible to non
      beta-lactam agents, but multiresistance is already prevalent in all regions.
      Surveillance of MRSA susceptibility patterns should be monitored to provide
      clinicians with the most current information regarding changes in resistance
      patterns.

PMID- 27873640
TI  - Plasmid-mediated multidrug resistance and virulence in an avian pathogenic
      Escherichia coli strain isolated in China.

PMID- 27873641
TI  - Plasmid-mediated quinolone resistance in Shigella isolates over a decade in
      India.

PMID- 27873642
TI  - MDRO Beijing Consensus Meeting Report: Global burden of multidrug-resistant
      organisms' current antimicrobial resistance problems in Asia-Pacific.
AB  - The International Society of Chemotherapy's Working Groups on Antibiotic
      Resistance and Antibiotic Stewardship convened a half-day workshop on the burden
      of multidrug-resistant organisms in the Asia-Pacific. This short review is a
      summary of their discussion and conclusions.

PMID- 27873644
TI  - Effects of clofazimine on planktonic and biofilm growth of Mycobacterium
      tuberculosis and Mycobacterium smegmatis.
AB  - Mycobacteria form lipid-rich biofilms that restrict the efficacy of antimicrobial
      chemotherapy, possibly necessitating the use of lipophilic antibiotics. In the
      current study, the activity of one such agent, clofazimine, against Mycobacterium
      tuberculosis and Mycobacterium smegmatis planktonic cells and biofilms was
      investigated. Minimum inhibitory concentrations (MICs) of clofazimine were
      determined for planktonic cultures, whilst minimum bactericidal concentrations
      (MBCs) were determined for planktonic, biofilm-producing and biofilm-encased
      organisms using standard bacteriological procedures. The effects of clofazimine
      on biofilm formation and the stability of pre-formed biofilm were measured using
      a crystal violet-based spectrophotometric procedure. In the case of M. smegmatis,
      clofazimine was found to be active against planktonic phase (MICs and MBCs of
      2.5mg/L and >20mg/L, respectively) and biofilm-producing organisms (MBC of
      2.5mg/L); clofazimine demonstrated greater activity against M. tuberculosis,
      corresponding values of 0.06, 5 and 0.3mg/L. Although clofazimine inhibited
      biofilm production both by M. tuberculosis and M. smegmatis (P<0.05 at >=0.07mg/L
      and >=0.3mg/L, respectively) and appeared to reduce the pre-formed M.
      tuberculosis biofilm, addition of antimicrobial agent to pre-existing biofilm
      matrices failed to kill biofilm-encased organisms. In conclusion, clofazimine is
      more effective against M. tuberculosis than against M. smegmatis, exhibiting
      bactericidal activity both for actively growing and slowly replicating bacilli
      but not for non-replicating organisms of both species.

PMID- 27873643
TI  - Detection of novel and reported mutations in the rpoB, katG and inhA genes in
      multidrug-resistant tuberculosis isolates: A hospital-based study.
AB  - The objective of this study was to detect mutations associated with isoniazid
      (INH) and rifampicin (RIF) resistance in Mycobacterium tuberculosis isolates from
      newly diagnosed and previously treated tuberculosis patients using a PCR-based
      DNA sequencing technique. Phenotypic drug susceptibility testing was performed
      using a BACTECTM MicroMGIT Culture System in 354 M. tuberculosis isolates. Among
      the 354 isolates, 18 were multidrug-resistant tuberculosis (MDR-TB). PCR-based
      DNA sequencing was performed targeting the rpoB gene for RIF and the whole of the
      katG gene and the promoter and coding region of the inhA gene for INH. Results
      were analysed using MultAlin analysis to identify the presence of polymorphisms
      or mutations by comparing with already available GenBank sequences. Only 37.5% of
      RIF-resistant isolates showed the presence of the most commonly reported mutation
      (Ser531Leu). The most commonly reported mutation (Ser531Leu) was detected in six
      MDR-TB isolates. The frequency of mutations associated with INH resistance was
      31.5% (17/54) and 29.6% (16/54) for katG and inhA, respectively. Comparing the
      relative distribution of mutations in the two target loci revealed that 12
      isolates (22.2%) had a mutation in both katG and inhA. Apart from previously
      reported mutations in the katG gene, there were three novel deletion and six
      novel substitution mutations. As reported in previous studies, Ser531Leu was the
      most common mutation detected in RIF-resistant isolates. The genetic mechanism of
      INH resistance in M. tuberculosis is highly complex involving several genes, and
      much remains to be explored to achieve a better understanding of this complex
      mechanism.

PMID- 27873645
TI  - Characterisation of extended-spectrum beta-lactamases among Klebsiella pneumoniae
      isolates causing bacteraemia and urinary tract infection in Mozambique.
AB  - The aim of this study was to determine the prevalence of extended-spectrum beta
      lactamase (ESBL)-producing Klebsiella pneumoniae isolated from urinary tract and
      bloodstream infections in a rural hospital in Manhica, Mozambique. ESBLs were
      investigated among ceftriaxone-non-susceptible K. pneumoniae clinical isolates
      recovered between 2004 and 2009. Characterisation of blaCTX-M, blaSHV, blaOXA and
      blaTEM genes was performed by PCR and sequencing. Epidemiological relationships
      were established by phylogenetic analysis, repetitive extragenic palindromic PCR
      (REP-PCR), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing
      (MLST), whilst plasmid transferability was evaluated by conjugation. In addition,
      the presence of class 1 and 2 integrons was studied. A total of 19 K. pneumoniae
      were analysed. The blaCTX-M-15 gene was found in all strains. Other ESBL genes
      were found concomitantly, including blaSHV-5, blaSHV-2, blaSHV-2A, blaSHV-12 and
      blaSHV-38. In addition, other beta-lactamases such as blaTEM-1 and blaOXA-30 were
      also detected. REP-PCR identified 15 different epidemiological profiles. MLST
      analysis also showed great variability of sequence types. The blaCTX-M-15 gene
      showed a high transfer capacity. The presence of class 1 integrons was high. High
      levels of multidrug resistance were also found. In conclusion, these data show
      the dominance of the CTX-M-type ESBL, particularly CTX-M-15, supporting its
      worldwide dissemination, including in areas with limited access to third
      generation cephalosporins. This finding is a matter of concern for clinical
      management as third-generation cephalosporins are an alternative for treating
      severe cases of multidrug-resistant infections in this community.

PMID- 27873646
TI  - Methicillin-resistant Staphylococcus aureus strains from Ghana include USA300.
AB  - The objective of this study was to provide baseline information on circulating
      methicillin-resistant Staphylococcus aureus (MRSA) clones in Ghana. Thirty MRSA
      isolates collected between 2010 and 2013 from patients and healthy carriers were
      characterised by DNA microarray analysis, staphylococcal protein A (spa) typing,
      multilocus sequence typing (MLST) and minimum inhibitory concentration (MIC)
      determination to 21 antimicrobial agents. Phenotypic resistance was detected to
      tetracycline (67%), norfloxacin (40%), moxifloxacin (37%), erythromycin (37%),
      clindamycin (33%), gentamicin (30%), kanamycin (30%) and ceftaroline (20%),
      whereas no resistance was observed for glycopeptides, linezolid, daptomycin and
      tigecycline. DNA microarray analysis showed that tet(M) (43%), tet(K) (33%),
      aphA3 (23%), aacA-aphD (17%) and erm(C) (13%) were the most prevalent resistance
      genes. ST88-IV (WA MRSA-2) (n=8), ST8-IV (USA300) (n=5) containing arginine
      catabolic mobile element (ACME) and Panton-Valentine leukocidin (PVL), and ST247
      I (North German/Iberian EMRSA) (n=4) were the most frequent clones detected. All
      MRSA contained sak and scn genes, one isolate (ST36-II) harboured the gene
      encoding the toxic shock syndrome toxin (TSST) and none contained exfoliative
      toxin genes. In conclusion, the relatively high levels of resistance to easily
      accessible non-beta-lactam agents further complicate the treatment of MRSA
      infections in Ghana. The occurrence of USA300 and other epidemic multidrug
      resistant MRSA clones in this African country is a matter of public health
      concern due to the lack of adequate infrastructures for MRSA surveillance and
      control in this geographical setting.

PMID- 27873647
TI  - The long-term effects of restrictive interventions on consumption and costs of
      antibiotics.
AB  - In the last decade, Slovenia introduced restrictive measures for some antibiotic
      classes in ambulatory care as well as regulatory interventions to reduce costs.
      The aim of this study was to analyse the effects of these interventions on
      consumption and costs of antibiotics in ambulatory care. Consumption data were
      expressed in defined daily doses/1000 inhabitants per day (DID), number of
      packages/1000 inhabitants per day and number of prescriptions/1000 inhabitants
      per year. In 2000, Slovenia introduced restrictive measures for prescription of
      amoxicillin/clavulanic acid (AMC) and fluoroquinolones, in 2005 for oral third
      generation cephalosporins and in 2009 for macrolides. Segmented regression
      analysis of interrupted time series was used to estimate the effects of
      restrictive interventions on antibiotic consumption. Total outpatient consumption
      of antibacterial drugs decreased by 29.65% from 20.27 DID in 1999 to 14.26 DID in
      2012. Three years after the introduction of restrictions, consumption of AMC,
      fluoroquinolones and macrolides decreased by 29.3%, 23.8% and 28.8%,
      respectively, compared with the year before the intervention, and of non
      restricted antibiotics by 3.3% (in 2003). Twelve years after the introduction of
      restrictive interventions, use of AMC and fluoroquinolones decreased by 28.1% and
      28.5%, respectively, and use of non-restricted antibiotics by 18.8% (in 2012). In
      the same time period, the costs of AMC and fluoroquinolones were reduced by 63.3%
      and 52.4%, respectively, and of non-restricted antibiotics by 46.9%. Restrictive
      interventions in ambulatory care are effective in reducing antibiotic consumption
      and costs. Restrictive interventions had a significantly greater impact on
      consumption 3 years post-intervention than after 12 years.

PMID- 27873648
TI  - Telavancin activity when tested by a revised susceptibility testing method
      against uncommonly isolated Gram-positive pathogens responsible for documented
      infections in hospitals worldwide (2011-2013).
AB  - The broth microdilution method for telavancin susceptibility testing was revised
      and now utilises DMSO as solvent for stock solution preparation and diluent for
      stock solution dilution, following CLSI guidelines for water-insoluble agents.
      The revised method also incorporates polysorbate 80 in the test medium to
      mitigate drug binding to plastics. This revised methodology provides more
      accurate and reproducible MIC determinations, which results in values lower than
      the previously established method. This study was conducted to re-establish
      telavancin potencies and susceptibility profiles (using updated interpretive
      criteria) against a collection of uncommon clinical pathogens (3821 isolates).
      Telavancin showed MIC50 values of 0.06mg/L against tested staphylococcal species
      (MIC50/90, 0.03/0.06mg/L; 98.1-100.0% susceptible), with lower results for
      Staphylococcus hominis (MIC50, <=0.015mg/L), Staphylococcus lugdunensis (MIC50,
      <=0.015mg/L) and Staphylococcus simulans (MIC50, 0.03mg/L). Vancomycin (MIC50,
      1mg/L), daptomycin (MIC50, 0.12-1mg/L) and linezolid (MIC50, 0.25-1mg/L) had
      MIC50 results at least four-fold higher than telavancin against CoNS.
      Streptococci (99.2-100.0% susceptible) displayed telavancin MIC50 values of
      <=0.015-0.03mg/L. Vancomycin (MIC50, 0.25-0.5mg/L) and linezolid (MIC50, 0.5
      1mg/L) had higher MIC50 results against streptococci, whilst daptomycin MIC50
      values varied from <=0.06mg/L to 0.5mg/L. Micrococcus, Listeria and
      Corynebacterium spp. were inhibited by telavancin at <=0.015, <=0.03 and
      <=0.06mg/L, respectively. Telavancin exhibited potent in vitro activity against
      this collection, greater than comparators (daptomycin, linezolid, vancomycin).
      This study provides new baseline MIC results for telavancin and confirms the
      spectrum and potency of telavancin against less commonly encountered Gram
      positive species.

PMID- 27873649
TI  - Antibacterial susceptibility of Escherichia coli among outpatients with community
      acquired urinary tract infection in Hamadan, Iran.
AB  - Escherichia coli is the main cause of community-acquired urinary tract infections
      (UTIs). The aims of the present study were to examine the susceptibility profile
      of E. coli causing UTIs and to identify factors associated with antimicrobial
      resistance. A cross-sectional study was conducted in Hamadan City, Iran, between
      2012 and 2013. Patients referred to Farshchian or Shahid Beheshti Hospitals and
      diagnosed with UTI caused by E. coli were enrolled in the study. Susceptibility
      testing to commonly used antimicrobial agents was performed by the disk diffusion
      method. Relevant data were abstracted, and analysis was performed to identify
      factors associated with antimicrobial resistance. A total of 154 patients were
      enrolled in the study. Among the respective number of E. coli isolates, the
      highest susceptibility was observed to nitrofurantoin (94.1%) and gentamicin
      (86.4%) and the lowest to amoxicillin/clavulanic acid (35.1%),
      trimethoprim/sulfamethoxazole (38.3%) and ciprofloxacin (51.9%). Twenty-four
      isolates (15.6%) were susceptible to all antimicrobial tested, 31 (20.1%) were
      resistant to one agent and 99 (64.3%) exhibited resistance to at least two
      different classes of antibiotics [multidrug-resistant (MDR) phenotype]. Patients
      with prior use of antibiotics during the past 3 months and those who had an
      episode of UTI in the past 2 years were at higher risk of being infected with MDR
      E. coli (P=0.034 and P=0.001, respectively). In conclusion, a substantial
      proportion of E. coli causing UTI exhibited a MDR phenotype. History of UTI and
      prior use of antibiotics were associated with increased risk of infection caused
      by MDR E. coli.

PMID- 27873650
TI  - The hidden resistome of retail chicken meat.

PMID- 27873651
TI  - Antibiotic susceptibility patterns and blaPER-1 beta-lactamase-producing
      Acinetobacter baumannii isolated from hospitalised patients.

PMID- 27873652
TI  - A hospital sewage ST17 Enterococcus faecium with a transferable Inc18-like
      plasmid carrying genes coding for resistance to antibiotics and quaternary
      ammonium compounds (qacZ).

PMID- 27873654
TI  - De novo induction of resistance against voriconazole in Aspergillus fumigatus.

PMID- 27873653
TI  - Variations in IS6 promoters alter the expression of carbapenem resistance in
      related strains of Acinetobacter baumannii.
AB  - The aim of this work was to investigate the role of the IS6 family of insertion
      sequences present upstream of blaOXA-58 in two clonally related carbapenem
      resistant Acinetobacter baumannii isolates obtained from paediatric cancer
      patients in Egypt. To determine their relatedness, the isolates were typed by
      pulsed-field gel electrophoresis (PFGE), and the intrinsic blaOXA-51-like gene
      was amplified and sequenced. Minimum inhibitory concentrations (MICs) to imipenem
      and meropenem was determined according to British Society of Antimicrobial
      Chemotherapy (BSAC) guidelines. PCR and sequencing of blaOXA-58 and the upstream
      and downstream regions was performed to determine the genetic environment. The
      two isolates were positive for the intrinsic blaOXA-64 gene, and the MICs for
      isolates AB-14298 and AB-P67 were 8mg/L and 64mg/L for imipenem and 2mg/L and
      16mg/L for meropenem, respectively. The blaOXA-58 gene in AB-14298 was flanked by
      ISAba3 interrupted with IS1006, whereas AB-P67 had ISAba3 interrupted by IS1008,
      both belonging to the IS6 family of insertion sequences. In conclusion, both
      IS1006 and IS1008 provided suitable promoter sequences for expression of the
      downstream blaOXA-58 gene.

PMID- 27873655
TI  - First report of blaOXA-23 in Acinetobacter baumannii isolates from Chilean
      hospitals.

PMID- 27873656
TI  - A novel plasmid carrying blaCTX-M-15 identified in commensal Escherichia coli
      from healthy pregnant women in Ibadan, Nigeria.
AB  - The aim of this study was to investigate the molecular characteristics of
      commensal Escherichia coli producing extended-spectrum beta-lactamases and
      showing fluoroquinolone resistance circulating in a healthy population in Ibadan,
      Nigeria. In total, 101 faecal samples from healthy pregnant women on the day of
      admission to hospital were collected and plated on eosin-methylene blue agar
      supplemented with cefotaxime. Genotyping demonstrated the presence of the blaCTX
      M-15 gene in all of the cefotaxime-resistant isolates (n=32), and there was
      circulation of prevalent clones. The aac(6')-Ib-cr, qnrS1, qepA1 and qnrB1 genes
      were identified in several strains. A novel plasmid supporting the spread of the
      blaCTX-M-15, blaTEM-1 and qnrS1 genes was identified in these isolates by
      complete DNA sequencing.

PMID- 27873657
TI  - Antimicrobial activity of beta-lapachone encapsulated into liposomes against
      meticillin-resistant Staphylococcus aureus and Cryptococcus neoformans clinical
      strains.
AB  - The aim of this study was to determine whether encapsulation of beta-lapachone
      (beta-lap) into liposomes interferes with its in vitro antimicrobial activity
      against meticillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus
      neoformans clinical strains. Liposomes (beta-lap:lipo or beta-lap:HPbeta-CD-lipo)
      were prepared using the hydration of thin lipid film method followed by
      sonication. The in vitro antimicrobial activities of beta-lap-loaded liposomes
      against MRSA and C. neoformans were evaluated using the microdilution method
      according to the Clinical and Laboratory Standards Institute (CLSI). The
      liposomes presented a mean particle size ranging from 88.7+/-1.5nm to 112.4+/
      1.9nm with a polydispersity index ranging from 0.255 to 0.340, zeta potential
      from -0.26+/-0.01mV to +0.25+/-0.05mV and drug encapsulation efficiency from
      97.4+/-0.3% to 98.9+/-0.4%. beta-Lap and beta-lap:HPbeta-CD had minimum
      inhibitory concentrations (MICs) ranging from 2mg/L to 4mg/L, whereas the MICs of
      beta-lap-lipo or beta-lap:HPbeta-CD-lipo ranged from 4mg/L to 16mg/L for the MRSA
      strains tested. beta-Lap and beta-lap:HPbeta-CD were able to inhibit fungal
      growth [MIC=2-8mg/L and minimum fungicidal concentration (MFC)=4-8mg/L]. However,
      beta-lap-lipo and beta-lap:HPbeta-CD-lipo were more efficient, with MICs and MFCs
      of <4mg/L. These findings suggest that the liposomal formulations tested do not
      interfere significantly with beta-lap antibacterial activity against MRSA and
      improve its antifungal properties against C. neoformans.

PMID- 27873658
TI  - Isolation of carbapenem-resistant Pseudomonas spp. from food.
AB  - Pseudomonas spp. are ubiquitous in nature. Carbapenem resistance in environmental
      isolates of members of this genus is thought to be rare but the exact resistance
      rate is unknown. In this study, carbapenem-resistant Pseudomonas spp. were
      isolated from chicken and pork samples and the mechanisms underlying the
      carbapenem resistance in these strains were investigated. A total of 16
      carbapenem-resistant Pseudomonas aeruginosa, Pseudomonas putida and Pseudomonas
      otitidis isolates were recovered from eight samples of chicken and pork. The
      isolates exhibited meropenem minimum inhibitory concentrations (MICs) of 8 to
      >=32mg/L and imipenem MICs of <0.5-16mg/L yet did not harbour any acquired
      carbapenemase genes. Meropenem resistance in various strains was found to be
      mediated by efflux systems only, whereas overexpression of MexAB-OprM efflux pump
      and lack of OprD porin were responsible for carbapenem resistance in P.
      aeruginosa. The intrinsic metallo-beta-lactamase gene blaPOM in P. otitidis and
      overexpression of the TtgABC efflux system in P. putida were also responsible for
      carbapenem resistance in these organisms. In conclusion, this study reports for
      the first time the isolation of carbapenem-resistant P. aeruginosa, P. otitidis
      and P. putida strains from food. The resistance mechanisms of these strains are
      rarely due to production of carbapenemases. Further selection of such carbapenem
      resistant Pseudomonas spp. in the environment and the risk by which they are
      transmitted to clinical settings are of great public health concern.

PMID- 27873659
TI  - Isolation of a point mutation associated with altered expression of the CmeABC
      efflux pump in a multidrug-resistant Campylobacter jejuni population of poultry
      origin.
AB  - The objective of this study was to investigate the antibiotic resistance
      phenotype of Campylobacter jejuni isolates from a poultry flock of broiler
      production in Spain. Isolates were characterised by RFLP-PCR of the flaA gene and
      multilocus sequence typing. Minimum inhibitory concentrations of quinolones,
      aminoglycosides, beta-lactams, tetracyclines, phenicols, macrolides and
      lincosamides were determined by Etest. Determinants of resistance and the
      regulatory region of the cmeABC operon were investigated in all isolates by PCR
      detection and sequencing. Expression of the CmeABC efflux pump was investigated
      by quantitative RT-PCR and accumulation assay. Based on their molecular markers,
      two different populations of C. jejuni were identified: one resistant to
      quinolones, beta-lactams and tetracyclines, considered multidrug-resistant (MDR);
      and another resistant only to tetracyclines. Both populations possessed the tetO
      gene, previously associated with tetracycline resistance. The blaOXA-61 gene was
      also present in both populations, although only the MDR population showed beta
      lactamase activity. In addition, MDR isolates possessed the Thr86Ile mutation in
      the gyrA gene responsible for quinolone resistance. Moreover, sequencing of the
      regulatory region of the cmeABC operon revealed the presence of the C-32->T
      mutation in the MDR isolates, which was accompanied by an increase in cmeA mRNA
      levels compared with the non-mutant population. In conclusion, this is the first
      report of the mutation C-32->T in the cmeABC operon in C. jejuni isolates of
      veterinary origin. This mutation is associated with overexpression of the CmeABC
      efflux pump in a MDR population and is possibly related to enhanced tolerance to
      antimicrobials that favours the development of resistance.

PMID- 27873660
TI  - Carbapenem-resistant Klebsiella pneumoniae infections in a Greek intensive care
      unit: Molecular characterisation and treatment challenges.
AB  - Acquisition of carbapenemase-producing Klebsiella pneumoniae (CP-Kp) strains
      poses a major threat to critically ill patients. The objectives of this study
      were to describe the epidemiology of CP-Kp isolates as well as the clinical
      outcome associated with the corresponding infections and to identify risk factors
      for mortality of intensive care unit (ICU) patients in a Greek hospital. A
      prospective, observational study was conducted in a nine-bed general ICU over a 2
      year period (April 2010-March 2012). Imipenem-resistant K. pneumoniae isolates
      recovered from clinical samples of ICU patients were prospectively collected and
      studied for the presence of carbapenemases. Isolates were submitted to molecular
      typing using pulsed-field gel electrophoresis (PFGE). In total, 61 CP-Kp isolates
      (48 KPC-producers and 13 VIM-producers) were recovered from 58 ICU patients. The
      majority of KPC-producers were classified into a single PFGE type, indicating
      potent clonal dissemination. Among the 32 infected patients, bacteraemia was
      diagnosed in 16. Tigecycline+colistin was the most common combination
      antimicrobial regimen. Infection-attributable mortality was 43.8%. Regarding
      mortality risk factors, non-survivors were older (P=0.080), all of them presented
      with septic shock (P=0.010) and they had higher Sepsis-related Organ Failure
      Assessment (SOFA) scores at infection onset (P=0.004) compared with survivors.
      Appropriate definitive treatment and combination regimens were not associated
      with patient survival. In conclusion, CP-Kp infections are associated with
      limited treatment options and high in-hospital mortality. Effective measures for
      preventing dissemination of respective isolates in the hospital setting are
      required.

PMID- 27873661
TI  - Increased frequency of linezolid resistance among clinical Enterococcus faecium
      isolates from German hospital patients.
AB  - Linezolid is an antibiotic of last resort for the treatment of infections with
      vancomycin-resistant enterococci (VRE). Here we report the increasing prevalence
      of linezolid resistance among clinical Enterococcus faecium strains from German
      hospital patients. Linezolid minimum inhibitory concentrations (MICs) were
      determined for 4461 clinical E. faecium strains isolated between 2008 and 2014.
      Isolates originated from the network of diagnostic laboratories collaborating
      with the National Reference Centre (NRC) for Staphylococci and Enterococci
      covering all German federal states. All linezolid-resistant isolates were
      determined by broth microdilution and confirmed by Etest as well as by analysing
      the 23S rDNA for putative mutations. Marker genes were determined by PCR.
      Genotyping was performed by SmaI macrorestriction analysis in pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST) for selected
      isolates. An increase in linezolid resistance was observed, from <1% in 2008 to
      >9% in 2014. Occasionally, outbreaks with linezolid-resistant VRE (ST117) were
      observed. In total, 232 (92.4%) of 251 linezolid-resistant E. faecium isolates
      (including 61 vanA and 29 vanB) contained the G2576T 23S rDNA mutation and showed
      a varying mixture of wild-type and mutated alleles per genome sufficient to
      confer linezolid resistance. In vitro growth experiments revealed a stable
      linezolid MIC. Of the 251 linezolid-resistant isolates, 5 were cfr-positive. In
      conclusion, these NRC data identified a country-wide ongoing trend of increasing
      linezolid resistance among clinical E. faecium isolates within the last 5 years.

PMID- 27873663
TI  - Intrapersonal mutation of rmpA and rmpA2: A reason for negative
      hypermucoviscosity phenotype and low virulence of rmpA-positive Klebsiella
      pneumoniae isolates.
AB  - Two Klebsiella pneumoniae isolates were simultaneously recovered from blood and
      urine cultures of the same patient. Both isolates were identical in genomic
      pulsotype by pulsed-field gel electrophoresis (PFGE). However, the
      hypermucoviscosity phenotype was confirmed in the blood strain but not the urine
      strain. A previously unrelated liver abscess K. pneumoniae hypermucoviscous
      isolate was used as a control. PCR, DNA cloning and sequencing for the plasmid
      borne rmpA and rmpA2 genes and the chromosome-borne rmpA gene (c-rmpA) revealed
      negative c-rmpA with natural frame-shift mutation of rmpA and rmpA2 genes in the
      urine strain. The blood strain was negative for c-rmpA with rmpA2 mutation but no
      mutation in rmpA. The control strain was positive for c-rmpA with rmpA2 mutation
      but no mutation in rmpA and showed the highest virulence in mouse lethality
      experiments [median lethal dose (LD50)=50CFU], which was followed by the blood
      strain (LD50=2.47*103CFU) and the urine strain (LD50>107CFU). The control and
      blood strains were highly serum resistant, whereas the urine strain was sensitive
      to serum killing. In conclusion, intrapersonal concurrent mutation of rmpA and
      rmpA2 genes in the absence of c-rmpA could be a reason for the negative
      hypermucoviscosity phenotype and low virulence in rmpA-positive K. pneumoniae.

PMID- 27873664
TI  - Genetic determinants of antimicrobial resistance in Streptococcus canis in
      France.

PMID- 27873662
TI  - Limited similarity between plasmids encoding CTX-M-1 beta-lactamase in
      Escherichia coli from humans, pigs, cattle, organic poultry layers and horses in
      Denmark.
AB  - CTX-M-1 is a common extended-spectrum beta-lactamase (ESBL) in Escherichia coli
      from animals and is often detected among human clinical isolates. The objective
      of this study was to investigate the epidemiological relationship between CTX-M-1
      producing E. coli isolated from patients and animals in Denmark between 2006 and
      2010. In total, 65 CTX-M-1-producing isolates from patients (n=22), pigs (n=21),
      cattle (n=4), organic poultry layers (n=3) and horses (n=15) were typed by pulsed
      field gel electrophoresis (PFGE). Plasmids harbouring blaCTX-M-1 were
      characterised by S1 PFGE, PCR-based replicon typing, plasmid multilocus sequence
      typing, restriction fragment length polymorphism, and sequencing. Human and
      animal strains were unrelated based on PFGE. IncI1 was more common in human
      isolates (13/22) than in animal isolates (7/43), whereas the opposite trend was
      observed for IncN (5/22 human isolates and 24/43 animal isolates). Full
      characterisation of the plasmids harbouring blaCTX-M-1 revealed host-specific
      patterns in the distribution of plasmid types, with specific IncI1, IncN and
      IncH1 plasmid subtypes being predominant in humans, livestock and horses,
      respectively. Three indistinguishable human, bovine and porcine IncI1/ST49
      plasmids had high nucleotide sequence homology and differed by the presence of
      IS66 elements in the bovine plasmid and the absence of one gene within the
      microcin-encoding operon in the human plasmid. In conclusion, this work suggests
      a minor contribution by animals to the occurrence of CTX-M-1 in human E. coli
      infections in Denmark during the study period.

PMID- 27873665
TI  - Use of veterinary antimicrobials in China and efforts to improve their rational
      use.

PMID- 27873666
TI  - Detection of an NDM-1-producing Acinetobacter bereziniae strain in Brazil.

PMID- 27873667
TI  - HACEK organisms exhibit low minimum inhibitory concentrations to ertapenem.

PMID- 27873668
TI  - An unusual PVL-positive MRSA strain in milk and dairy products from a region of
      South Italy.

PMID- 27873669
TI  - Pseudomonas aeruginosa carrying blaCTX-M-2 in Brazil: The occurrence of 'high
      risk clones'?

PMID- 27873670
TI  - Resistance to antimalarial drugs: An endless world war against Plasmodium that we
      risk losing.
AB  - The objective of this review was to describe the 'state of the art' of Plasmodium
      falciparum resistance to the main antimalarial drugs. A brief note on Plasmodium
      vivax is also included. Resistance of P. falciparum to the various antimalarials
      has a long history of hits and misses. During the last 60 years, the pace at
      which this parasite has developed resistance to antimalarial drugs has exceeded
      the pace at which new drugs have been developed. In the last decade, the
      introduction of artemisinin-based combination therapies (ACTs) as a first-line
      drug treatment for non-complicated P. falciparum malaria had led to extraordinary
      results in disease control, especially in sub-Saharan Africa. However, the
      emergence and spread of resistance to artemisinin in Southeast Asia jeopardise
      these results. In conclusion, the possible spread of artemisinin resistance in
      Africa should be considered as an epochal disaster.

PMID- 27873671
TI  - Importance of early detection of vancomycin-resistant subpopulations in
      apparently susceptible meticillin-resistant Staphylococcus aureus clinical
      isolates.
AB  - This study aimed to investigate the presence of vancomycin-non-susceptible
      subpopulations in apparently susceptible meticillin-resistant Staphylococcus
      aureus (MRSA) and the ability of these isolates to develop into homogeneously
      resistant strains. Vancomycin MICs of 200 clinical MRSA isolates were determined
      using agar dilution (AD) and spiral gradient endpoint (SGE) technique. Isolates
      with an MIC<=2mg/L but displaying subpopulations with an MIC>2mg/L by SGE were re
      tested by Etest and PAP-AUC and were incubated with 2mg/L vancomycin for 2 weeks.
      MIC testing was repeated weekly by AD, Etest and SGE to observe progression to
      non-susceptibility. A total of 17.5% and 16.0% of isolates were non-susceptible
      to vancomycin (MIC>2mg/L) by SGE and AD, respectively. Eight isolates (4%)
      displayed a resistant subpopulation; five met the definition of hVISA by PAP-AUC.
      The initial Etest MIC for these isolates was 2mg/L, but resistant subpopulations
      were observed in only three isolates on prolonged incubation. MICs of all eight
      isolates increased rapidly in the presence of vancomycin, reaching >=3.0mg/L by
      Day 7 and >=4mg/L after 14 days by all three methods. The prevalence of
      vancomycin-non-susceptible MRSA was high, and non-susceptibility developed
      rapidly in seemingly susceptible isolates with covert subpopulations. These were
      effectively detected by SGE. With increasing reports of vancomycin clinical
      failure, early detection of potentially non-susceptible isolates before or early
      in vancomycin therapy is essential to avoid further resistance development and
      poor clinical outcomes. SGE offers a novel and cost-effective technique for
      detection of potentially non-susceptible strains.

PMID- 27873673
TI  - Comparative evaluation of tigecycline susceptibility testing methods for
      Acinetobacter baumannii and Enterobacteriaceae.
AB  - The objectives of this study were to recommend suitable susceptibility testing
      methods for tigecycline for clinical laboratory use and to evaluate differences
      in tigecycline susceptibility between carbapenem-susceptible and carbapenem-non
      susceptible isolates. Broth microdilution (BMD) was used as the reference method
      to evaluate MIC Test Strip (MTS), agar dilution, VITEK(r) 2 and disk diffusion
      testing methods for tigecycline against Acinetobacter baumannii and
      Enterobacteriaceae. MIC50/90 values (minimum inhibitory concentrations for 50%
      and 90% of the isolates, respectively) of A. baumannii and Enterobacteriaceae
      were, respectively, 2/4MUg/mL and 0.5/4MUg/mL by BMD, 1.5/3MUg/mL and 0.5/3MUg/mL
      by MTS, 2/4MUg/mL and 1/8MUg/mL by agar dilution and 2/4MUg/mL and 2/8MUg/mL by
      VITEK(r) 2. Essential agreement for A. baumannii/Enterobacteriaceae detected by
      MTS, agar dilution and VITEK(r) 2 methods was 96.0/97.3%, 98.0/97.3% and
      94.0/63.9%, respectively. Categorical agreement for A.
      baumannii/Enterobacteriaceae detected by MTS, agar dilution, VITEK(r) 2 and disk
      diffusion methods was 90.0/91.8%, 72.0/93.7%, 62.0/86.5% and 72.0/81.2%,
      respectively. No very major errors were found for all isolates by the four
      methods evaluated. Major error rates were produced by VITEK(r) 2 (for
      Enterobacteriaceae) and by disk diffusion (for A. baumannii and
      Enterobacteriaceae). Tigecycline susceptibility of carbapenem-susceptible and
      carbapenem-non-susceptible isolates was 85.2% and 83.6% (chi2=0.15, P>0.05) using
      the reference method. In conclusion, in this study MTS showed the best
      correlation with BMD for tigecycline MICs. Based on in vitro testing, tigecycline
      can be considered an equally useful choice for infections caused by carbapenem
      susceptible and carbapenem-non-susceptible isolates.

PMID- 27873672
TI  - Triazole-resistant Aspergillus fumigatus harbouring G54 mutation: Is it de novo
      or environmentally acquired?
AB  - Triazole resistance in Aspergillus fumigatus develops in patients with chronic
      lung diseases receiving long-term azole therapy or by environmental selection of
      resistant A. fumigatus. Here we report for the first time the isolation of
      triazole-resistant A. fumigatus (TRAF) harbouring the G54E mutation from
      environmental samples in India, Romania and Tanzania. This mutation in the cyp51A
      azole target gene of A. fumigatus is so far considered as de novo occurring in
      patients due to prolonged exposure to azoles. A total of 81 soil and woody debris
      samples from India, Romania and Tanzania were processed for detection of TRAF and
      determination of their susceptibility to medical triazoles and fungicides. cyp51A
      sequencing and real-time PCR were performed for detection of mutations. The
      isolates were genotyped by microsatellite typing. Overall, 25% of samples (20/81)
      from India, Romania and Tanzania harboured TRAF. Of the 20 samples harbouring
      TRAF, a single resistance mechanism, the G54E mutation, was found in 16 samples
      from three countries. This mechanism was responsible for 46.4% of resistant
      isolates from Tanzania, 30.4% from Romania and 20.0% from India. The G54E
      isolates revealed high MICs of itraconazole and posaconazole and were cross
      resistant to agricultural fungicides. The majority of the Romanian and Tanzanian
      G54E isolates had an identical genotype. The present report describes the genetic
      heterogeneity of TRAF strains harbouring the G54E mutation in the environment of
      India, Romania and Tanzania. It may be anticipated that long-term exposure of A.
      fumigatus to fungicides may induce selection of G54 mutants in the environment.

PMID- 27873674
TI  - Meticillin-resistant Staphylococcus aureus (MRSA) antibiogram: How inaccurate
      have our estimates been?
AB  - The objective of this study was to determine the accuracy of antimicrobial
      resistance patterns reported by the Australian Group on Antimicrobial Resistance
      (AGAR) established using surveys of just the first 100 Staphylococcus aureus
      isolates from each participating hospital. Patterns of resistance of a survey
      sample of S. aureus isolates collected prospectively from five Queensland
      hospitals participating in the AGAR biennial national survey, using the first 100
      isolates diagnosed from each test year, were tested. Meticillin-resistant S.
      aureus (MRSA) antibiograms for five antimicrobials commonly used to treat
      outpatients established from a sample have underestimated the true level of
      resistance by 13-21 percentage points. Conversely, inpatient antibiograms have
      significantly overestimated the resistance level. Random selection of 100
      isolates from all isolates did not provide valid resistance patterns for
      outpatients or inpatients. Nearly 50% of resistance demonstrated in all inpatient
      isolates and about 45% of resistance in all outpatient isolates was due to AUS
      2/3-like, EMRSA-15-like and MRSA unclassified. In conclusion, testing S. aureus,
      and in particular MRSA, for resistance levels to commonly prescribed
      antimicrobials is under/over-estimated in Australia because of a faulty annual
      sampling method that failed to consider the effect of endemic phenotypes (AUS-2/3
      like and EMRSA-15-like). MRSA represents one-third of all S. aureus AGAR
      isolates. Endemic phenotypes bias the antibiogram patterns when small consecutive
      sampling (first 100 samples) is used and this bias remains even when samples are
      selected at random. A minimum sample of 6 months of isolates must be used to
      accurately establish a national antibiogram.

PMID- 27873675
TI  - Susceptibility patterns of uropathogens identified in hospitalised children with
      community-acquired urinary tract infections in Thrace, Greece.
AB  - Urinary tract infections (UTIs) are common infections associated with
      considerable morbidity and mortality, particularly in paediatric patients. The
      alarmingly increasing antimicrobial resistance of contemporary uropathogens in
      children necessitates the re-evaluation of antibiotic treatment. We evaluated
      uropathogens isolated from children hospitalised due to a community-acquired UTI
      over a 5.5-year period in a university hospital of Northern Greece and their
      antibiotic susceptibility patterns. The antibiotic susceptibility of uropathogens
      was compared by patient sex and age. Bacterial identification and antibiotic
      susceptibility testing were performed by the automated VITEK(r) 2 system and the
      Kirby-Bauer method. Overall, 221 urinary isolates were identified from 218
      children with a documented UTI, including 170 (76.9%) Escherichia coli, 17 (7.7%)
      Proteus spp., 15 (6.8%) Klebsiella spp., 9 (4.1%) Pseudomonas aeruginosa, 4
      (1.8%) Enterococcus faecalis, 2 (0.9%) Enterobacter spp., 2 (0.9%) Morganella
      morganii and 2 (0.9%) Serratia fonticola. Comparing antibiotic susceptibilities
      of E. coli isolates by age [<=2 years vs. >2 years] and sex did not show any
      significant differences. Only 80 (49.1%) of the 163 tested E. coli isolates were
      found to be susceptible to ampicillin, whereas susceptibility to
      amoxicillin/clavulanic acid (AMC), ampicillin/sulbactam,
      trimethoprim/sulfamethoxazole and nitrofurantoin was 78.3%, 78.9%, 75.3% and
      96.9%, respectively. Parenteral second- and third-generation cephalosporins,
      aminoglycosides and carbapenems were highly active against almost all
      uropathogens. We conclude that ampicillin should not be used for empirical
      therapy of paediatric community-acquired UTIs in our region. AMC and oral second
      generation cephalosporins cover ca. 80% of uropathogenic E. coli, whilst
      nitrofurantoin is an appealing option for UTI chemoprophylaxis.

PMID- 27873676
TI  - Pattern of antibiotic prescription and resistance profile of common bacterial
      isolates in the internal medicine wards of a tertiary referral centre in Nigeria.
AB  - Indiscriminate and excessive use of antibiotics is the major driver to the
      development of bacterial resistance, which is now a global challenge. Information
      regarding antibiotic use in Nigerian hospitals is lacking. This study examined
      the pattern of antibiotic prescription in a tertiary hospital in Nigeria. In a
      retrospective survey, case records of patients who were admitted into the medical
      wards over a 6-month period were reviewed. A pre-formed questionnaire was
      administered that sought information such as sociodemographic data, drug data,
      basis of prescription and other relevant information on all patients who received
      antibiotics. Data were analysed using SPSS for Windows v.16. Of 412 patients
      admitted into the internal medicine ward during the study period, 202 (49.0%)
      received antibiotics, of whom 125 (61.9%) received more than one antibiotic.
      Overall there were 334 antibiotic prescriptions. Community-acquired pneumonia
      (67/202; 33.2%) was the leading cause of antibiotic prescription, and ceftriaxone
      (132/334; 39.5%) was the most commonly prescribed antibiotic. The parenteral
      route was the commonest route of administration (270/334; 80.8%) and most of the
      prescriptions were empirical (323/334; 96.7%). Antimicrobial resistance among
      common bacterial isolates was noted. Inappropriate antibiotic prescription is
      common. There was frequent use of third-generation cephalosporins as empirical
      therapy, with de-escalation in only a handful of cases. This highlights the need
      for introduction of antibiotic guidelines.

PMID- 27873677
TI  - Changes in patterns of antibiotic use in Chinese public hospitals (2005-2012) and
      a benchmark comparison with Sweden in 2012.
AB  - Changes in patterns of antibiotic use in Chinese hospitals before and after
      intensive nationwide interventions are reported and compared with Chinese
      national targets and antibiotic use in Swedish hospitals. Chinese data were
      collected quarterly and yearly from selected patient prescriptions/medical
      records and medicines inventory control systems from 15 hospitals (2005-2012).
      Swedish data were extracted from a 2010-point prevalence survey and 2009-2012
      sales data from seven university hospitals. An interrupted time series with
      segmented regression analysis was used to measure changes in patterns of
      antibiotic use in Chinese hospitals before and after the interventions. Following
      the 2011 interventions, significant reductions in antibiotic use in Chinese
      hospitals were seen: the proportion of prescriptions with antibiotics decreased
      4.7% (P=0.03) and the proportion of medical records with antibiotic prescription
      decreased 7.3% (P=0.04). The proportions of prescriptions and medical records
      with antibiotics in Chinese hospitals in 2012 were 10% and 50%, respectively, and
      remained much higher than Swedish hospitals (1.1% in DDD for outpatients and 34%
      in number of patients for inpatients). Inpatient consumption in Chinese hospitals
      dropped significantly from 910 DDD/1000 inpatient days in 2008 to 473 in 2012
      (588 in Swedish hospitals). Antibiotics are being used less frequently in Chinese
      hospitals, broad-spectrum antibiotics are still preferred, and overall usage is
      higher than Sweden. A significant reduction in overall inpatient antibiotic
      consumption was observed after the interventions. It is not possible to identify
      whether the changes have resulted in less inappropriate antibiotic use. Further
      studies are needed.

PMID- 27873678
TI  - Vancomycin-resistant enterococci: Troublemaker of the 21st century.
AB  - The emergence of multidrug-resistant and vancomycin-resistant enterococci during
      the last decade has made it difficult to treat nosocomial infections. Although
      various enterococcal species have been identified, only two (Enterococcus
      faecalis and Enterococcus faecium) are responsible for the majority of human
      infections. Vancomycin is an important therapeutic alternative against multidrug
      resistant enterococci but is associated with a poor prognosis. Resistance to
      vancomycin dramatically reduces the therapeutic options for enterococcal
      infections. The bacterium develops resistance by modifying the C-terminal d
      alanine of peptidoglycan to d-lactate, creating a d-Ala-d-Lac sequence that
      effectively reduces the affinity of vancomycin for the peptidoglycan by 1000
      fold. Moreover, the resistance genes can be transferred from enterococci to
      Staphylococcus aureus, thereby posing a threat to patient safety and also a
      challenge for treating physicians. Judicious use of vancomycin and broad-spectrum
      antibiotics must be implemented, but strict infection control measures must also
      be followed to prevent nosocomial transmission of these organisms. Furthermore,
      improvements in clinical practice, rotation of antibiotics, herbal drugs,
      nanoantibiotics and the development of newer antibiotics based on a
      pharmacogenomic approach may prove helpful to overcome dreadful vancomycin
      resistant enterococcal infections.

PMID- 27873679
TI  - Vancomycin-intermediate resistance in Staphylococcus aureus.
AB  - Vancomycin-intermediate Staphylococcus aureus (VISA) and its precursor hetero
      VISA (hVISA) were discovered almost 20 years ago and have continued to be a
      stumbling block in the chemotherapy of methicillin-resistant S. aureus (MRSA).
      Unlike vancomycin resistance mediated by the van gene in enterococci and
      staphylococci, VISA is generated by accumulation of mutations. It displays
      diverse and intriguing genetic mechanisms underlying its resistance phenotype.
      Here we make a brief note on our recent understanding of the genetics of hVISA,
      VISA and the newly discovered phenotype 'slow VISA' (sVISA).

PMID- 27873680
TI  - Antimicrobial susceptibility in hospitals in Hong Kong: The current status 2009
      2011.
AB  - Hospitals in Hong Kong, like many hospitals in the world, are constantly
      challenged by the increasing rate of non-susceptible and multidrug-resistant
      organisms (MDROs). Accurate and timely surveillance is essential for effective
      control. The Hospital Authority of Hong Kong has developed a comprehensive
      antimicrobial susceptibility monitoring system that utilises data obtained from
      all of its 38 hospitals. In this review, the susceptibility pattern of more than
      320000 isolates covering the period 2009-2011 will be discussed. Special
      attention will be paid to MDROs.

PMID- 27873682
TI  - Optimal duration of antimicrobial therapy in ventilator-associated pneumonia:
      What is the role for procalcitonin?
AB  - Hospital-acquired pneumonia (HAP) is the major cause of hospital-acquired
      infections in critically ill patients. Up to 90% of intensive care unit episodes
      of HAP occur in mechanically ventilated patients, who may develop what is termed
      ventilator-associated pneumonia (VAP). An appropriate duration of antimicrobial
      therapy is crucial in the management of HAP: on the one hand, delay in
      administration of proper therapy has been associated with an increased risk of
      treatment failure and mortality; on the other hand, unnecessary prolongation of
      antimicrobial treatment may favour the emergence of multidrug-resistant bacteria
      and increase healthcare costs. In this review, we discuss the evidence and
      recommendations from international guidelines for the management of VAP and focus
      on randomised controlled trials comparing the clinical efficacy of a short-course
      vs. an extended-course antimicrobial regimen for the treatment of VAP in adults.
      In these trials, short-course regimens were as effective and safe as long-course
      regimens for the treatment of VAP, provided that infection was not due to
      difficult-to-treat micro-organisms such as non-fermenting Gram-negative bacilli.
      In addition, strategies incorporating individualised stop-points for antibiotics,
      i.e. clinical features or biomarkers such as procalcitonin, were shown to reduce
      antibiotic exposure, healthcare costs and the risk of developing antimicrobial
      resistance, without negatively affecting other outcomes.

PMID- 27873681
TI  - Antimicrobial prophylaxis in dentistry.
AB  - Use of antibiotics both in humans and animals runs along with effects that can
      contribute to the spread of antibiotic resistance. Although several available
      guidelines for antibiotic treatment have been published to date, clinical
      practice in dentistry and particularly in oral surgery is not free from
      controversies regarding antibiotic prophylaxis. Antibiotic coverage to prevent
      infectious endocarditis, joint prostheses infections or local infections requires
      a careful evaluation of the patient condition, associated risks and other aspects
      that could influence the decision. It is of great relevancy for oral surgeons and
      for dentists in general to know exactly what they are up against. Here we review
      the literature regarding prophylactic use of antimicrobials in dentistry.

PMID- 27873683
TI  - Antibiotic stewardship challenges in the management of community-acquired
      infections for prevention of escalating antibiotic resistance.
AB  - Community-acquired infections, including respiratory tract infections (RTIs) and
      urinary tract infections (UTIs), represent a major burden for most healthcare
      systems, partially due to ineffective or inappropriate antibiotic treatment
      leading to clinical failure, which often requires alternative antibiotics for
      cure. Appropriate antimicrobial use not only maximises clinical success in the
      treatment of community-acquired infections, but also minimises unintended
      consequences such as resistance development or collateral damage. This article
      outlines a range of antibiotic stewardship strategies and other preventative
      approaches that support the management of community-acquired infections, based on
      existing antibiotic use for community-acquired infections and the current
      resistance patterns among common RTI and UTI pathogens.

PMID- 27873684
TI  - Antifungal drug resistance in Candida species.
AB  - Invasive Candida infections are well established infectious entities of
      immunocompromised or critically ill patients and are characterised by high
      morbidity and mortality. Owing to the common eukaryotic structure of fungi and
      humans, a limited number of antifungal drugs is available for therapeutic
      purposes. In this unsatisfactory scenario, the emergence of drug resistance
      represents an important health problem. Failure of antifungal treatment can be
      related to host factors, to the pharmacokinetic and pharmacodynamic parameters of
      the drug, or to morphological, reproductive modalities and biofilm production of
      the fungus itself. Innate or acquired antifungal resistance derives from the
      presence or onset of molecular mechanisms related to the toxic activity of the
      drug itself. The resulting resistance can thus be extended to different molecules
      of the same class according to a greater or lesser affinity of the molecules for
      the target. In addition, non-specific cellular mechanisms of extrusion of toxic
      substances, such as overexpression of efflux pumps, can play a role involving
      different antifungal classes. Here we briefly review the current antifungal
      susceptibility testing methods and their usefulness as predictors of antifungal
      resistance in Candida spp., focusing on assessment of the involved molecular
      mechanisms.

PMID- 27873686
TI  - Investigation of tigecycline bactericidal activity: Optimisation of laboratory
      testing.
AB  - The objectives of this study were to optimise the conditions for bactericidal
      testing of tigecycline and to investigate its bactericidal activity against
      clinical isolates of Gram-positive and Gram-negative bacteria. Tigecycline is the
      first in a new class of glycylcycline antibiotics exhibiting in vitro activity
      against a broad range of bacteria, including multidrug-resistant organisms. Its
      bactericidal activity in vitro has not been extensively investigated using
      multiple test conditions. Five growth media comprising Mueller Hinton broth,
      Minimum Essential Medium of Eagle, Ham F-12, RPMI 1640 and Iso-Sensitest broth
      (ISB) with and without surfactant (Tween 80) were investigated in vitro to assess
      tigecycline bactericidal activity. Clinical isolates of meticillin-resistant
      Staphylococcus aureus, meticillin-susceptible S. aureus, Escherichia coli,
      Klebsiella pneumoniae and Enterococcus spp., representing the majority of
      clinically relevant bacteria, were evaluated for the impact of test conditions on
      the tigecycline minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC), ISB with 0.02% Tween 80 most efficiently demonstrated the
      bactericidal action of tigecycline when evaluated in 64 well-characterised
      clinical isolates and was considered as the optimal bactericidal test medium.
      Using this condition, tigecycline approached 56% bactericidal activity with
      3log10 reduction in CFUs at 72h incubation. Bactericidal action increased to 80%
      of strains when 2log10 reduction was used as the endpoint. Only Enterococcus spp.
      showed no bactericidal response in this analysis. Tigecycline exhibited a
      bactericidal effect in vitro against Gram-positive and Gram-negative bacteria. At
      the tested in vitro conditions, tigecycline MICs were unchanged regardless of the
      different test media used.

PMID- 27873685
TI  - Preventing the introduction of meticillin-resistant Staphylococcus aureus into
      hospitals.
AB  - The objective of this review was to provide an up-to-date account of the
      interventions used to prevent the introduction of meticillin-resistant
      Staphylococcus aureus (MRSA) from the expanding community and livestock
      reservoirs into hospitals in the USA, Denmark, The Netherlands and Western
      Australia. A review of existing literature and local guidelines for the
      management of MRSA in hospitals was performed. In Denmark, The Netherlands and
      Western Australia, where the prevalence of MRSA is relatively low, targeted
      admission screening and isolation of predefined high-risk populations have been
      used for several decades to successfully control MRSA in the hospital.
      Furthermore, in Denmark and The Netherlands, all identified MRSA carriers undergo
      routine decolonisation, whereas only carriers of particularly transmissible or
      virulent MRSA clones are subjected to decolonisation in Western Australia. In the
      USA, which continues to be a high-prevalence MRSA country, policies vary by state
      and even by hospital, and whilst guidelines from professional organisations
      provide a framework for infection control practices, these guidelines lack the
      authority of a legislative mandate. In conclusion, the changing epidemiology of
      MRSA, exemplified by the recent emergence of MRSA in the community and in food
      animals, makes it increasingly difficult to accurately identify specific high
      risk groups to screen for MRSA carriage. Understanding the changing epidemiology
      of MRSA in a local as well as global context is fundamental to prevent the
      introduction of MRSA into hospitals.

PMID- 27873687
TI  - Occurrence of azole-resistant species of Aspergillus in the UK environment.
AB  - The aim of this study was to survey environmental isolates of Aspergillus
      resistant to azoles in azole-treated and naive areas to determine whether
      resistance could be related to azole treatment history. Aspergillus fumigatus was
      sampled from the centre of a large city and from fields with known azole history.
      Azole resistance was determined and sequencing was performed to identify strains
      and mutations in the cyp51A gene. Azole resistance was detected in azole-treated
      field isolates but not in urban isolates (P=0.038). In addition, an azole
      resistant isolate of Neosartorya fischeri was isolated. These results support the
      hypothesis that agricultural azole use may lead to resistance in environmental
      fungi of clinical importance. We report the first environmental UK TR34/L98H
      isolate of A. fumigatus.

PMID- 27873688
TI  - Evaluation of in vitro susceptibility trends to vancomycin and daptomycin by
      strain type of Staphylococcus aureus causing bloodstream infections.
AB  - In total, 718 consecutive clinical meticillin-resistant Staphylococcus aureus
      (MRSA) isolates from 2006 to 2010 and 417 clinical meticillin-susceptible S.
      aureus (MSSA) isolates from mid-2007 to 2010 were evaluated. Isolates were from
      blood cultures obtained from separate patients in Detroit, MI, and were tested
      for in vitro susceptibility trends to vancomycin and daptomycin by molecular
      strain type. The MRSA pulsed-field gel electrophoresis (PFGE) results showed that
      290 (40.4%) were USA100, 296 (41.2%) were USA300 and the remaining isolates were
      non-USA100/300. Vancomycin minimum inhibitory concentrations (MICs) by Etest
      [mean+/-standard deviation (S.D.) 1.55+/-0.26mg/L] in MRSA isolates showed no
      significant change over the 5-year period within all strain types, whilst
      daptomycin MICs by Etest (mean+/-S.D. 0.51+/-0.25mg/L) showed a significant
      downward trend across time (r=-0.243; P<0.001), with this trend occurring among
      all PFGE groups. For MSSA, a significant decrease in MICs to vancomycin was found
      by Etest (r=-0.160; P=0.001) and conversely a significant increase in daptomycin
      MICs by Etest was found (r=0.146; P=0.028). The results of this study showed that
      changes in MIC were not specific to strain molecular type. For vancomycin, there
      was no change in MRSA MICs and a decrease in MSSA MICs for blood isolates. For
      daptomycin, MICs decreased in MRSA and increased in MSSA blood isolates over the
      study period.

PMID- 27873689
TI  - Eugenol-induced suppression of biofilm-forming genes in Streptococcus mutans: An
      approach to inhibit biofilms.
AB  - Streptococcus mutans is well documented as a major aetiological agent of dental
      caries. The ability to form a biofilm on tooth surfaces is the major virulence
      factor of this bacterium. The objective of this study was to evaluate the effect
      of eugenol on suppression of biofilm- and quorum sensing (QS)-related genes of S.
      mutans and to determine its putative mode of action. Eugenol was evaluated for
      its inhibitory activity against virulence properties such as adherence and
      biofilm formation. Morphological changes in the architecture of S. mutans and in
      the biofilm were analysed and observed using confocal laser scanning microscopy
      and transmission electron microscopy. The effects of eugenol on expression of
      biofilm- and QS-related genes (gtfB, gtfC, comDE, smu630, vicR, brpA, ftf, relA,
      gbpB and spaP) were checked by quantitative real-time PCR (qRT-PCR). The present
      data revealed that eugenol at a sub-minimum inhibitory concentration (sub-MIC)
      significantly downregulated the expression of tested genes but did not affect
      bacterial growth. These results suggest that a sub-MIC of eugenol can effectively
      suppress virulence genes. Thus, the results indicated that eugenol can inhibit
      caries-associated biofilm and showed its therapeutic potential against oral
      biofilm.

PMID- 27873690
TI  - Urinary tract infection in Uruguayan children: Aetiology, antimicrobial
      resistance and uropathogenic Escherichia coli virulotyping.
AB  - Uropathogenic Escherichia coli (UPEC) is the most frequent cause of urinary tract
      infection (UTI). Virulence factors (VFs) of UPEC in children are not well known.
      Circulating antibiotic resistance mechanisms in the community are increasing. In
      this study, the aetiological agents of UTI and antibiotic resistance mechanisms
      of 124 strains isolated from urine cultures from children with community-acquired
      UTI were determined. Virulotyping of isolated E. coli strains was also described.
      beta-Lactam, fluoroquinolone and sulfonamide resistance genes as well as
      integrons were detected by PCR. E. coli phylogenetic groups and 25 VFs were
      sought by multiplex PCR. E. coli was the most frequent aetiological agent
      (88.7%), of which 48.2% belonged to phylogenetic group D and 35.5% to group B2.
      Moreover, 81.8% were considered UPEC and >93% had virulence structures, with
      kpsMTII, fimH and iutA being the most frequent. Most of the E. coli isolates were
      susceptible to amoxicillin/clavulanic acid (AMC) (87.3%), nitrofurantoin (97.3%),
      cefuroxime and third-generation cephalosporins (100%). Resistance levels to
      oxyimino-cephalosporins were higher in non-E. coli isolates, with circulation of
      integrons, blaCTX-M-2 and blaCMY-2 detected in the community. Moreover, 8.1% of
      isolates were resistant to fluoroquinolones, with qnrB found in two isolates.
      Resistance to trimethoprim/sulfamethoxazole was found in 37.9% of isolates, with
      85.5% harbouring sul genes. E. coli isolated from children with UTI presented
      high rates of VFs. Nitrofurantoin, AMC and cefuroxime would be suitable
      antibiotics to treat UTI in children. However, the presence of integrons
      (fundamentally class 1) and circulation of broad-spectrum beta-lactamases in the
      community makes continuous surveillance necessary.

PMID- 27873691
TI  - Antimicrobial and biocide resistance of bacteria in a Lebanese tertiary care
      hospital.
AB  - The environment in a Lebanese tertiary-level care hospital was examined for
      bacterial contamination. In total, 8 open-air and 62 surface samples were taken
      and CFU were enumerated. Morphologically different isolates (n=104) were obtained
      and tested for resistance to a wide range of antibiotics by the Kirby-Bauer disc
      diffusion method. Minimum bactericidal concentrations of isolates to seven
      different biocides used within this facility were also determined using both
      qualitative and quantitative methods. Gram-positive bacteria (82.7% of isolates)
      were encountered more often than Gram-negative bacteria (17.3%), and the genus
      Staphylococcus was most prevalent among isolates (59.6% of the isolates). Gram
      positive isolates showed the highest resistance to penicillin (60.6%),
      clindamycin (54.5%) and ceftazidime (39.4%); the lowest frequencies of resistance
      were seen with vancomycin (0% of isolates), nitrofurantoin (3.5%), tetracycline
      (12.1%) and ciprofloxacin (12.1%). The prevalence of meticillin-resistant
      Staphylococcus aureus (MRSA) and meticillin-resistant coagulase negative
      staphylococci among all environmental samples was 3.8% and 11.5% of isolates,
      respectively. All Gram-negative isolates were multidrug-resistant (MDR). With
      respect to biocides, the highest frequency of resistance was to quaternary
      ammonium compounds (QACs) (13.5% of isolates) and the lowest frequency of
      resistance was to QAC/biguanide complex (<1% of isolates) and Anios DVA (3.8%).
      MDR bacteria can pose a serious threat in the hospital environment, showing the
      need for prudent use of antibiotics and correct infection control procedures.

PMID- 27873692
TI  - Assessment of the in vitro synergy of daptomycin plus linezolid against multidrug
      resistant enterococci.
AB  - The widespread incidence of enterococci resistant to ampicillin, vancomycin and
      aminoglycosides, the first-line anti-enterococcal antibiotics, has made the
      treatment of severe enterococcal infections difficult and alternatives should be
      explored. We investigated the activity of daptomycin combined with linezolid
      against three Enterococcus faecalis and four Enterococcus faecium strains
      resistant to standard drugs used for therapy. Minimum inhibitory concentrations
      (MICs) were determined by the broth dilution method. Drug interactions were
      assessed by the checkerboard and time-kill methods. Synergy was defined by a
      fractional inhibitory concentration index (FICI) of <=0.5 or a >=2log10CFU/mL
      killing at 24h with the combination in comparison with killing by the most active
      single agent. Indifference was defined by a FICI>0.5-4.0 or a 1-2log10CFU/mL
      killing compared with the most active single agent. MICs of daptomycin were 2
      4MUg/mL for E. faecalis and 2-8MUg/mL for E. faecium. MICs of linezolid were 1
      2MUg/mL for all bacteria. In the checkerboard assay, five isolates showed
      synergism (FICI<0.5) and two showed indifference (FICIs of 0.53 and 2). Killing
      studies revealed synergy of daptomycin plus linezolid against four isolates (2.2
      3.7log10CFU/mL kill) and indifference (1.1-1.6log10CFU/mL kill) for the other
      three strains. Antagonism was not observed. In conclusion, the combination of
      daptomycin and linezolid had a synergistic or indifferent effect against
      multidrug-resistant enterococci. Additional studies are needed to explore the
      potential of this combination for severe enterococcal infections when first-line
      antibiotic combinations cannot be used.

PMID- 27873693
TI  - blaTEM and vanA as indicator genes of antibiotic resistance contamination in a
      hospital-urban wastewater treatment plant system.
AB  - Four indicator genes were monitored by quantitative PCR in hospital effluent (HE)
      and in the raw and treated wastewater of the municipal wastewater treatment plant
      receiving the hospital discharge. The indicator genes were the class 1 integrase
      gene intI1, to assess the capacity of bacteria to be involved in horizontal gene
      transfer processes; blaTEM, one of the most widespread antibiotic resistance
      genes in the environment, associated with Enterobacteriaceae; vanA, an antibiotic
      resistance gene uncommon in the environment and frequent in clinical isolates;
      and marA, part of a locus related to the stress response in Enterobacteriaceae.
      Variation in the abundance of these genes was analysed as a function of the type
      of water, and possible correlations with cultivable bacteria, antimicrobial
      residue concentrations, and bacterial community composition and structure were
      analysed. HE was confirmed as an important source of blaTEM and vanA genes, and
      wastewater treatment showed a limited capacity to remove these resistance genes.
      The genes blaTEM and vanA presented the strongest correlations with culturable
      bacteria, antimicrobial residues and some bacterial populations, representing
      interesting candidates as indicator genes to monitor resistance in environmental
      samples. The intI1 gene was the most abundant in all samples, demonstrating that
      wastewater bacterial populations hold a high potential for gene acquisition.

PMID- 27873694
TI  - In vitro activity of colistin against Stenotrophomonas maltophilia.
AB  - Colistin is one of the few antimicrobials that retains activity against multidrug
      resistant Gram-negative bacteria. However, the emergence of colistin resistance
      has been described recently. The aims of this study were to determine the
      activity of colistin against isolates of Stenotrophomonas maltophilia. In total,
      641 S. maltophilia clinical isolates were obtained from single patients admitted
      to a university hospital in Buenos Aires city, Argentina, between the years 1996
      and 2013. Susceptibility to colistin was determined by the agar dilution method.
      An increase in colistin resistance from 8% in 1996 to 45% in 2013 was observed,
      which correlated with a marked increase in colistin consumption of 11.4-fold
      during the same period.

PMID- 27873695
TI  - Analysis of plasmid-mediated quinolone resistance genes in clinical isolates of
      the tribe Proteeae from Argentina: First report of qnrD in the Americas.
AB  - To analyse the occurrence and prevalence of plasmid-mediated quinolone resistance
      (PMQR) genes in the tribe Proteeae, 81 isolates (65 Proteus spp., 12 Morganella
      morganii and 4 Providencia stuartii) consecutively collected in 66 hospitals
      belonging to the WHONET-Argentina Resistance Surveillance Network were studied.
      Of the 81 isolates, 50 (62%) were susceptible to quinolones [43/65 (66%) Proteus
      spp. and 7/12 (58%) M. morganii). The remaining 31 isolates (22 Proteus spp., 5
      M. morganii and all P. stuartii) showed high-level resistance to nalidixic acid
      (NAL) and decreased susceptibility or resistance to ciprofloxacin. All NAL
      resistant isolates harboured mutations associated with quinolone resistance
      (MAQRs) in both gyrA (S83I/R) and parC (S80I/R), and some also had MAQRs in gyrB
      (S464Y/F). The unique PMQR gene detected was qnrD, which was found in 2/81
      isolates (Proteus mirabilis Q1084 and Proteus vulgaris Q5169), giving a
      prevalence of 2.5% in Proteeae. These two isolates were from different
      geographical regions and both harboured MAQRs in gyrA and parC. The qnrD genes
      were located on the related plasmids pEAD1-1 (2683bp) and pEAD1-2 (2669bp).
      Plasmid pEAD1-1 was 100% identical to pCGH15 and differed in only three
      nucleotides from pDIJ09-518a, which were previously found in clinical isolates of
      P. mirabilis (China) and Providencia rettgeri (France), respectively, whilst
      pEAD1-2 was not previously described. The extended-spectrum beta-lactamase CTX-M
      2 was found in 27% (22/81) of the isolates and was significantly associated with
      quinolone resistance but not with qnrD (only P. mirabilis Q1084 expressed CTX-M
      2). This is the first report of qnrD in the Americas.

PMID- 27873696
TI  - Emergence of plasmid mediated carbapenemase OXA-48 in a Klebsiella pneumoniae
      strain in Algeria.
AB  - A carbapenem resistant Klebsiella pneumoniae strain was isolated in October 2011
      in the pediatric unit of the Hopital central de l'armee in Algeria, this strain
      have been confirmed for the production of OXA-48 carbapenemase. The blaOXA-48
      gene was located on a self conjugative plasmid of 70kb. Multilocus sequence
      typing indicated the presence of the sequence type ST-307. This is the first
      isolation of OXA-48-producing K. pneumoniae in Algeria.

PMID- 27873697
TI  - First cases of KPC-type carbapenemase-producing bacteria in patients in New
      Zealand hospitals.
AB  - The emergence and global spread of Klebsiella pneumoniae carbapenemases (KPCs) is
      a significant public health problem. Between October 2010 and July 2013, KPC
      producing K. pneumoniae were isolated from four patients in New Zealand
      hospitals. These cases are the first known isolations of KPC-producing organisms
      in New Zealand. All four patients were transferred from, or had recently been in,
      hospitals in countries where KPC-producing organisms are prevalent (China, India,
      Greece and Italy). The blaKPC-2 gene was identified in the isolates from three
      patients and blaKPC-3 was identified in the isolate from the remaining patient.
      The isolates belonged to different multilocus sequence type clonal complexes,
      usually those prevalent in the country in which the patient had been previously
      hospitalised. Currently in New Zealand, the common factor associated with having
      a KPC-producing organism is prior hospitalisation in another country where these
      organisms are prevalent.

PMID- 27873698
TI  - Determinants of an effective antibiotic campaign: Lessons from Hong Kong.
AB  - Hong Kong launched a publicity campaign on the use of antibiotics and antibiotic
      resistance in March/April 2011. Two population surveys were conducted in November
      2010 (N=1569; response rate 69.2%) and June 2011 (N=1527; response rate 66.6%)
      before and after the campaign, respectively, to evaluate its impact. Adults aged
      >=18 years were asked about their knowledge and attitude related to antibiotic
      use and antibiotic resistance. Information obtained from health professionals had
      the highest mean impact score. There was a significant increase in the proportion
      of respondents knowing that antibiotics could not cure influenza (from 58.0 to
      65.0%; P<0.001) or viral infections (from 24.9 to 29.0%; P=0.002). Over one
      quarter (27.7%) of respondents could recall the campaign, mostly through
      announcement of public interest (API) on television/radio. After regression
      analysis, age, personal hygiene practices in daily life, and the attitude that
      everyone had a role to play in alleviating the problem of antimicrobial
      resistance were found to be associated with campaign awareness.

PMID- 27873700
TI  - Emergence of NDM-1 in a clinical isolate of Pantoea agglomerans from India.

PMID- 27873699
TI  - In vitro susceptibility of Gram-negative isolates from patients with urinary
      tract infections in Vietnam: Results from the Study for Monitoring Antimicrobial
      Resistance Trends (SMART).

PMID- 27873701
TI  - First description of fexA-positive meticillin-resistant Staphylococcus aureus
      ST398 from calves in Portugal.

PMID- 27873703
TI  - In vitro activity of daptomycin against isolates of vancomycin-resistant
      enterococci.

PMID- 27873702
TI  - Emergence of genetically related NDM-1-producing Providencia rettgeri strains in
      Argentina.

PMID- 27873704
TI  - Alarming and increasing prevalence of multidrug-resistant Pseudomonas aeruginosa
      among healthcare-associated infections in China: A meta-analysis of cross
      sectional studies.
AB  - A number of studies have reported on the prevalence of multidrug-resistant
      Pseudomonas aeruginosa (MDR-PA) among healthcare-associated infections (HAIs) in
      China; however, the exact rate of MDR-PA is unclear due to different definitions.
      Therefore, this meta-analysis was conducted to explore the prevalence of MDR-PA
      among HAIs in China based on an international recommended standard. Medline,
      Ovid, Cochrane Library, China National Knowledge Infrastructure (CNKI) and
      Wanfang databases were systematically searched and papers published before
      February 2014 providing exact data on MDR-PA in the Chinese population were
      identified. Overall effects, subgroup analysis and sensitivity analysis were
      performed using Stata v.13.0 software. Twenty-six studies were finally included.
      The overall prevalence of MDR-PA was 29.0% (95% confidence interval 24.6-33.4%).
      The rate of MDR-PA increased over time (P<0.001). The prevalence of MDR-PA was
      higher among patients in intensive care units (ICUs) (41.4%) than among non-ICU
      patients (24.1%) (P<0.001). In conclusion, the present meta-analysis
      comprehensively evaluated the prevalence of MDR PA in China and the findings
      suggest that MDR-PA should receive more attention.

PMID- 27873705
TI  - Analysis of 5-year trends in daptomycin activity tested against Staphylococcus
      aureus and enterococci from European and US hospitals (2009-2013).
AB  - This study evaluated daptomycin activity trends among meticillin-resistant
      Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) over a 5
      year period (2009-2013). Consecutive, unique patient isolates of clinical
      significance were collected in 67 European (EU) (17 nations) and 145 US medical
      centres and were susceptibility tested in a central reference laboratory against
      daptomycin and various comparators by CLSI broth microdilution methods. MIC
      results were interpreted according to EUCAST and CLSI breakpoint criteria (2014).
      A total of (EU/USA) 14245/22967 S. aureus (26.3/49.8% MRSA), 3043/2848
      Enterococcus faecalis (1.6/3.5% vancomycin-resistant) and 1827/1537 Enterococcus
      faecium (29.5/77.7% vancomycin-resistant) were evaluated. Isolates were mainly
      from complicated skin and skin-structure infections (40%) and bacteraemia (32%).
      The highest MRSA rates were found in Portugal (66.3%), Russia (52.2%) and the USA
      (49.8%), whereas the highest rates of vancomycin-resistant E. faecium (VREFM)
      were observed in the USA (77.7%), Poland (63.1%) and Ireland (54.5%). VREFM and
      vancomycin-resistant E. faecalis (VREF) were observed in 15 and 8 EU nations,
      respectively. Daptomycin susceptibility rates were (EU/USA) 99.94/99.97%,
      100.0/99.7% and 100.0/99.96% for S. aureus, E. faecium and E. faecalis,
      respectively. Daptomycin was very active against MRSA (MIC50/90, 0.25/0.5mg/L in
      Europe and USA), VREF (MIC50/90 of 0.5/1mg/L and 1/2mg/L in Europe and USA,
      respectively) and VREFM (MIC50/90, 2/2mg/L in Europe and USA). Among MRSA, only
      6/6 (0.19/0.05%) daptomycin-non-susceptible isolates were observed in Europe (six
      cities in four countries)/USA (six states), with no increasing trend over the
      study period. Only two daptomycin-non-susceptible VRE were identified, both E.
      faecium from the USA.

PMID- 27873706
TI  - Genetic diversity of oxytetracycline-resistant bacteria and tet(M) genes in two
      major coastal areas of South Korea.
AB  - This study aimed to analyse the prevalence and genetic diversity of the tet(M)
      resistance gene as well as the species composition of oxytetracycline-resistant
      bacteria in coastal areas of South Korea. Both culturable and non-culturable
      bacterial communities were sampled in 2010 and 2011 within two coastal areas
      (Wando and Geoje). tet(M) and 16S rRNA gene sequences were obtained by PCR and
      sequencing and were used for phylogenetic analyses. Quantitative PCR (qPCR) was
      performed to determine the prevalence of tet(M) in sampled areas. Phylogenetic
      analyses revealed high heterogeneity of tet(M) sequences between Wando and Geoje
      areas. Sequences found in Wando were highly similar to each other and were
      similar to sequences found in Japanese aquaculture sites. A larger diversity of
      tet(M) sequences was obtained from natural assemblage in Geoje. qPCR showed a
      high prevalence of tet(M) in Wando's aquaculture sites (up to 10-2gene copies per
      16S rRNA copy) and for industrial sites in Geoje (up to 10-3gene copies per 16S
      rRNA copy). 16 rRNA-based identification showed that Vibrio sp. and
      Photobacterium sp. were the most representative species in Wando, whereas in
      Geoje a broader range of species was found, with several isolates identified as
      pathogenic Acinetobacter, Aeromonas and Klebsiella. Altogether, these results
      showed a high prevalence of tet(M) in both sites, and different origins of
      contamination were identified. Because several pathogenic strains of
      oxytetracycline-resistant bacteria were reported for the first time, these
      results strongly warrant further analyses and actions to prevent contamination
      events by antibiotics in South Korea.

PMID- 27873707
TI  - Characterisation of beta-lactam resistance mediated by blaZ in staphylococci
      recovered from captive and free-ranging wallabies.
AB  - Staphylococci are commensal organisms of animals, but some species are
      opportunistic pathogens that are resistant to almost all antimicrobial agents in
      clinical use. Bacterial resistance to beta-lactam antimicrobial agents is
      widespread and has been investigated in species isolated from humans in addition
      to food production and companion animals. However, minimal progress has been made
      towards identifying reservoirs of beta-lactam-resistant staphylococci in
      wildlife. This study was aimed at investigating and characterising beta-lactamase
      resistance from staphylococci of wallaby origin. Staphylococci from free-ranging
      and captive wallabies were assessed for their phenotypic susceptibility to beta
      lactam antimicrobial agents prior to sequence analysis of their blaZ and blaR1
      genes. Deduced amino acid sequences were classified according to the Ambler
      molecular characterisation method, assigned a protein signature type and compared
      with sequences generated from previous studies involving isolates from humans,
      cattle and companion animals. All BlaZ sequences identified in this study were
      assignable to a pre-existing beta-lactamase class and protein signature type,
      including the more recently discovered protein signature type 12. Three major
      phylogenetic groups were resolved upon phylogenetic analysis against published
      BlaZ sequences. This study has found antibiotic-resistant staphylococci both in
      free-ranging and captive wallaby populations and these bacteria harbour blaZ
      variants that are different to those recovered from humans, cattle and companion
      animals. Further studies of staphylococci from non-traditional sources are
      required in order to enhance our knowledge of the epidemiology of antibiotic
      resistance genes.

PMID- 27873708
TI  - Antimicrobial resistance and resistance mechanisms of Enterobacteriaceae in ICU
      and non-ICU wards in Europe and North America: SMART 2011-2013.
AB  - Intensive care units (ICUs) are often described as hotbeds of antimicrobial
      resistance, with high rates of extended-spectrum beta-lactamase (ESBL)-producing
      and multidrug-resistant (MDR) Enterobacteriaceae. Data from the SMART study were
      used to examine differences between the susceptibility of Enterobacteriaceae from
      ICU and non-ICU wards in Europe and North America. In total, 21,470
      Enterobacteriaceae isolates from intra-abdominal and urinary tract infections
      were collected at 90 sites in 20 European and North American countries in 2011
      2013. Susceptibility and ESBL phenotypes were determined using the CLSI broth
      microdilution method and breakpoints. Susceptibility was lower and ESBL and MDR
      rates were higher in ICUs, with much greater ICU/non-ICU differences in Europe
      than North America. Susceptibility was lower and ESBL and MDR rates were higher
      in Europe than in North America in both patient locations. Resistance among
      Enterobacteriaceae in Europe was largely driven by Klebsiella pneumoniae, which
      had high rates of ESBLs (41.2% in ICUs; mostly CTX-M) and carbapenemases (13.2%;
      mostly KPC and OXA). For all Enterobacteriaceae combined, only ertapenem and
      amikacin inhibited >90% of isolates in ICUs in both regions. In North America,
      ertapenem, imipenem and amikacin inhibited >90% of K. pneumoniae from ICUs,
      whereas in Europe only amikacin did. ESBL and MDR rates varied considerably
      within Europe. Antimicrobial resistance was higher in Europe than North America,
      especially in ICUs. Further surveillance at the country, hospital and even
      patient ward level, and investigation of reasons for these findings, would be
      useful for the development of effective strategies to reduce antimicrobial
      resistance in ICUs.

PMID- 27873709
TI  - Antimicrobial resistance genotypes and phenotypes from multidrug-resistant
      bacterial wound infection isolates in Cambodia.
AB  - This study aimed to identify the molecular determinants responsible for
      antibiotic resistance among human wound isolates in Cambodia. Staphylococcus spp.
      (n=10) and a variety of Gram-negative isolates (n=21) were taken from a larger
      collection of wound isolates collected during 2011-2013 and were analysed for the
      presence of >230 resistance determinants using a broad-spectrum DNA microarray.
      These isolates were chosen to represent the species most commonly found in wound
      isolates referred during this time and to include some of the most resistant
      strains. Resistance determinants detected among the staphylococci included blaZ
      (90%), mecA (100%), erm(B) (70%), erm(C) (20%), tet(38) (90%), tet(K) (40%),
      tet(Lp) (10%), tet(M) (20%), lnu(A)/lin(A) and lnu(B)/lin(B) (10% each),
      msr(A)/msr(B)/msr(SA) (10%), norA (80%) and dfrA (10%). Eleven different beta
      lactamase genes were detected among the Gram-negative bacteria, including genes
      encoding the TEM (48%), CTX-M-1 (48%), CTX-M-9 (5%), SHV (5%) and VEB (10%)
      families of broad-spectrum and extended-spectrum beta-lactamase enzymes, as well
      as the carbapenemase gene blaOXA-23. Forty additional genes were also detected in
      the Gram-negative isolates conferring resistance to aminoglycosides (11 genes),
      phenicols (5 genes), macrolides [4 genes, including mph(A)/mph(K) (10%)],
      lincosamides [lnu(F)/lin(F), lnu(G)/lin(G)], tetracycline (4 genes), rifampicin
      [arr (29%)], quaternary amines [qacEDelta1 (43%)], quinolones [qnrS (14%) and
      qnrB (5%)], sulfonamides [sul1 (29%), sul2 (38%) and sul3 (10%)], streptothricin
      (sat2) and trimethoprim (6 genes). The results obtained here provide a snapshot
      of the broad variety of resistance determinants currently circulating within
      Cambodia.

PMID- 27873710
TI  - Molecular mechanisms of clarithromycin resistance in Mycobacterium abscessus
      complex clinical isolates from Venezuela.
AB  - In this study, 26 clinical isolates of Mycobacterium abscessus complex strains
      were characterised using available identification algorithms for the three
      species (M. abscessus, M. massiliense and M. bolletii) and the genotypic
      characteristics of clarithromycin (CLR) resistance were determined. Strains were
      identified by PCR restriction fragment length polymorphism analysis of the hsp65
      and erm(41) gene sequences. Susceptibility to CLR was determined by the broth
      microdilution method. The mechanism of resistance to this macrolide was evaluated
      by sequencing the erm(41) and rrl genes. Mutations and/or deletions associated
      with resistance to CLR as determined in this study were those that have been
      previously described. No constitutive resistance to CLR was found, however 35%
      (9/26) of the M. abscessus complex strains tested had a functional inducible
      erm(41) gene. Based on sequencing of this gene, the strains of M. abscessus were
      separated into six sequevars, of which only two are consistent with those
      previously reported. In conclusion, we demonstrated that the low percentage of
      strains with a resistant phenotype to CLR was due only to an inducible resistance
      mechanism conferred by the erm(41) gene and not to mutations in the rrl gene. CLR
      can still be useful for treatment in some Venezuelan patients infected with a
      member of the M. abscessus group, but drug resistance testing and/or molecular
      analysis must precede the prescription of this antibiotic.

PMID- 27873711
TI  - In vivo horizontal dissemination of the blaKPC-2 gene carried on diverse genetic
      platforms among clinical isolates of Enterobacteriaceae.
AB  - This study investigated the molecular characteristics of six blaKPC-positive
      Enterobacteriaceae recovered from three patients in Argentina. Antimicrobial
      susceptibility testing was performed following Clinical and Laboratory Standards
      Institute (CLSI) 2014 recommendations. Molecular characterisation of the isolates
      was performed by biparental conjugation, PCR, sequencing, S1 nuclease
      restriction, and Southern blot hybridisation with a blaKPC probe using standard
      protocols and conditions. The isolates studied were as follows. Case 1:
      Escherichia coli (ECO-P1) and Klebsiella pneumoniae (KPN-P1) isolated from a
      rectal swab harboured blaKPC-2 in transposon Tn4401a on non-typeable and non
      conjugative plasmids. Case 2: Enterobacter cloacae (ECL-P2) and K. pneumoniae
      (KPN-P2) were isolated from two blood cultures. blaKPC-2 was found in a novel
      genetic variant of ISKpn8-blaKPC-2-ISKpn6-like on conjugative plasmids of IncL/M
      type. Case 3, Citrobacter freundii (CFR-P3) and Klebsiella oxytoca (KOX-P3) were
      isolated from skin and skin-structure infection. The blaKPC gene was detected on
      ISKpn8-DeltablaTEM-blaKPC-2-ISKpn6-like located on an IncA/C conjugative plasmid.
      CFR-P3 and KOX-P3 harboured blaPER-2 in addition to the blaKPC gene. In
      conclusion, we document the horizontal dissemination of blaKPC-2 from diverse
      Enterobacteriaceae clinical isolates with different genetic backgrounds. This is
      the first report of E. coli harbouring blaKPC associated with Tn4401a in
      Argentina.

PMID- 27873713
TI  - Emergence of OXA-48-producing Escherichia coli in the Caribbean islands.

PMID- 27873712
TI  - Efficacy of tigecycline-colistin combination in the treatment of carbapenem
      resistant Klebsiella pneumoniae endocarditis.
AB  - Here we discuss the efficacy of colistin-tigecycline combination in the treatment
      of multidrug-resistant (MDR) Klebsiella pneumoniae infective endocarditis (IE).
      We report a case of a 67-year-old head-injured patient who developed a carbapenem
      resistant K. pneumoniae IE. The patient was treated with colistin-tigecycline
      combination, with a favourable outcome. In conclusion, colistin-tigecycline
      combination may be a possible combination in the therapy of IE caused by MDR
      Enterobacteriaceae.

PMID- 27873714
TI  - Investigation of a possible outbreak of NDM-5-producing ST16 Klebsiella
      pneumoniae among patients in Denmark with no history of recent travel using whole
      genome sequencing.

PMID- 27873715
TI  - Antibiotic resistance in Bartonella bacilliformis clinical isolates from an
      endemic area of Peru.

PMID- 27873716
TI  - The outer membrane protein CD is associated with resistance to penicillins in
      Moraxella catarrhalis.

PMID- 27873717
TI  - National Reference Laboratory for Antimicrobial Resistance in India: The need of
      the hour.

PMID- 27873718
TI  - The challenge of antiparasitic resistance.

PMID- 27873719
TI  - Treatment options for methicillin-resistant Staphylococcus aureus (MRSA)
      infection: Where are we now?
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infection continues to be a
      substantial global problem with significant associated morbidity and mortality.
      This review summarises the discussions that took place at the 4th MRSA Consensus
      Conference in relation to the current treatment options for serious MRSA
      infections and how to optimise whichever therapy is embarked upon. It highlights
      the many challenges faced by both the laboratory and clinicians in the diagnosis
      and treatment of MRSA infections.

PMID- 27873720
TI  - High burden of antimicrobial drug resistance in Asia.
AB  - The rapid development of antimicrobial resistance among micro-organisms is a
      serious public health concern. Moreover, the dissemination of antibiotic
      resistant bacteria makes this issue a global problem, and Asia is no exception.
      For example, since New Delhi metallo-beta-lactamase (NDM)-producing
      Enterobacteriaceae were identified in India, further spread of NDM has become a
      worldwide threat. However, the epidemiology of antibiotic-resistant bacteria in
      Asia may be different to other regions, and clinical condition may be worse than
      in western countries. Antibiotic-resistant bacteria, including community-acquired
      and hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA),
      vancomycin-intermediate S. aureus (VISA), vancomycin-resistant enterococci,
      macrolide- and penicillin-resistant Streptococcus pneumoniae, extend-spectrum
      beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae,
      carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas
      aeruginosa and Acinetobacter spp., are becoming prevalent in many countries in
      Asia. Moreover, the prevalence of each antibiotic-resistant bacterium in each
      country is not identical. This review provides useful information regarding the
      critical condition of antibiotic resistance in Asia and emphasises the importance
      of continuous surveillance of resistance data.

PMID- 27873721
TI  - The growing challenges of antibacterial drug resistance in Ethiopia.
AB  - Infectious diseases of bacterial origin are a major cause of morbidity and
      mortality in developing countries such as Ethiopia. To minimise such burdens,
      proper use of antibiotics has played a vital role and saved countless lives.
      However, use of antimicrobials as therapeutic agents is compromised by the
      potential development of drug-resistant micro-organisms. Currently, antimicrobial
      drug resistance has become a public health concern both in developing and
      developed countries. Antimicrobial drug resistance is dramatically accelerated
      when antimicrobials are misused. This is critical, especially in developing
      countries where they are not only misused but are often underused due to
      financial constraints. Although large-scale studies on antimicrobial resistance
      in Ethiopia have not yet been conducted, the available reports indicate a trend
      towards increasing resistance rates among pathogens such as Escherichia coli,
      Shigella spp., Salmonella spp. and Staphylococcus aureus to commonly prescribed
      antibiotics, including ampicillin, amoxicillin, penicillin, tetracycline and
      trimethoprim/sulfamethoxazole. This review summarises the existing data on
      antibacterial drug resistance in this country.

PMID- 27873723
TI  - Comparison of antimicrobial resistance phenotypes and genotypes in
      enterotoxigenic Escherichia coli isolated from Australian and Vietnamese pigs.
AB  - This study aimed to compare the antibiogram phenotype and carriage of
      antimicrobial resistance genes (ARGs) of 97 porcine multidrug-resistant (MDR)
      enterotoxigenic Escherichia coli (ETEC) isolates obtained from Vietnam and 117
      porcine MDR-ETEC obtained from Australia, two countries with different
      antimicrobial regulation systems. An antimicrobial resistance index (ARI) was
      calculated to quantify their potential significance to public health. Both
      Vietnamese and Australian isolates had moderate to high levels of resistance to
      commonly used antibiotics (ampicillin, tetracycline and sulphonamides). None of
      the Australian isolates were resistant to fluoroquinolones or third-generation
      cephalosporins and none possessed associated plasmid-mediated ARGs. However,
      23.1% of Australian isolates were resistant to gentamicin owing to ARGs
      associated with apramycin or neomycin resistance [e.g. aac(3)-IV] that impart
      cross-resistance to gentamicin. Whilst Vietnamese isolates carried aminoglycoside
      ARGs, 44.4% of commercial pig isolates were resistant to gentamicin in comparison
      with 0% of village pig isolates. The plasmid-mediated fluoroquinolone ARG qnrB
      was commonly detected in Vietnamese isolates (52.3% commercial, 44.1% village),
      but phenotypic resistance was low (3.2% and 11.8%, respectively). The mean ARI
      for Vietnamese isolates (26.0) was significantly different (P<0.001) from the
      mean ARI for Australian isolates (19.8), primarily reflecting fluoroquinolone
      resistance in the former collection. This comparison suggests the effectiveness
      of regulations that slow the dissemination of 'critical' resistance by
      restricting the availability of important classes of antimicrobials.

PMID- 27873722
TI  - Antimicrobial susceptibility among Gram-positive and Gram-negative isolates
      collected in Europe between 2004 and 2010.
AB  - Here we report on the in vitro activity of a suite of antimicrobial agents
      against Gram-negative and Gram-positive pathogens collected in Europe between
      2004 and 2010 as part of the Tigecycline Evaluation and Surveillance Trial
      (T.E.S.T.). Clinical and Laboratory Standards Institute (CLSI) broth
      microdilution methodologies were used to determine minimum inhibitory
      concentrations. CLSI interpretive criteria were applied for all antimicrobial
      agents to establish susceptibility; European Committee on Antimicrobial
      Susceptibility Testing (EUCAST) breakpoints were used for tigecycline. In total,
      46,921 Gram-negative and 19,174 Gram-positive isolates were included in this
      study. Extended-spectrum beta-lactamases increased in proportion from 15.7% to
      21.1% among Klebsiella pneumoniae and from 9.7% to 16.1% among Escherichia coli
      isolates between 2004-2007 and 2010. E. coli susceptibility decreased to most
      antimicrobials but it remained highly susceptible (>98%) to tigecycline and
      meropenem. Acinetobacter baumannii susceptibility also decreased to most agents.
      The proportion of meticillin-resistant Staphylococcus aureus (MRSA) decreased
      from 25.7% to 19.4% over the study period. Antimicrobial susceptibility has
      decreased among many of the pathogens observed in the T.E.S.T. surveillance study
      between 2004-2007 and 2010.

PMID- 27873724
TI  - Engineered honey: In vitro antimicrobial activity of a novel topical wound care
      treatment.
AB  - Surgihoney is a novel engineered organic honey product for wound care. Its
      antimicrobial activity can be controlled and adjusted by the engineering process,
      allowing preparation of three different potencies, labelled Surgihoney 1-3.
      Susceptibility testing of a range of wound and ulcer bacterial isolates to
      Surgihoney by the disc diffusion method, minimum inhibitory concentration (MIC)
      and minimum bactericidal concentration (MBC) determination, and time-kill
      measurements by time suspension tests were performed. Surgihoney demonstrated
      highly potent inhibitory and cidal activity against a wide range of Gram-positive
      and Gram-negative bacteria and fungi. MICs/MBCs were significantly lower than
      concentrations likely to be achieved in topical clinical use. The topical
      concentration of Surgihoney in wounds was estimated at ca. 500g/L. MICs/MBCs for
      Staphylococcus aureus were 32/125g/L for Surgihoney 1 and 0.12/0.25g/L for
      Surgihoney 3. Cidal speed depended on potency, being 48h for Surgihoney 1 and
      30min for Surgihoney 3. Maintenance of the Surgihoney inoculum preparation for up
      to a week demonstrated complete cidal activity and no bacterial persistence.
      Surgihoney has wide potential as a highly active topical treatment combining the
      effects of the healing properties of honey with the potent antimicrobial activity
      of the engineered product for skin lesions, wounds, ulcers and cavities. It is
      highly active against multidrug-resistant bacteria. It is more active than other
      honeys tested and is comparable with chemical antiseptics in antimicrobial
      activity.

PMID- 27873725
TI  - Spectrum and patterns of antimicrobial resistance of uropathogens isolated from a
      sample of hospitalised Lebanese patients with urinary tract infections.
AB  - A retrospective study was carried out to assess the current distribution and
      antimicrobial susceptibility patterns of uropathogens isolated from patients with
      community-acquired (CA) or hospital-acquired (HA) urinary tract infections (UTIs)
      who were admitted to the largest governmental hospital in Beirut City (Lebanon)
      in 2009-2012. Overall, 292 uropathogens were isolated. Enterobacteriaceae
      constituted 81% of the isolated uropathogens, with Escherichia coli, Klebsiella
      pneumoniae and Proteus mirabilis being the most reported species. Moreover, 37%
      of the isolated uropathogens produced extended-spectrum beta-lactamases (ESBLs).
      ESBL-producing strains were more prevalent in CA-UTIs than in HA-UTIs. In the CA
      UTI group, ESBL-producing strains were more prevalent in older patients (age >60
      years), male patients and patients with diabetes mellitus, urinary
      catheterisation and benign prostatic hyperplasia. Uropathogens isolated from CA
      UTI and HA-UTI had similar resistance patterns. The highest resistance rates were
      found for ampicillin, amoxicillin/clavulanic acid, trimethoprim/sulfamethoxazole
      and ciprofloxacin. Imipenem, nitrofurantoin and piperacillin/tazobactam showed
      good overall activity against the isolated uropathogens. Of the isolated non-ESBL
      producing E. coli, 29% were found to be multidrug-resistant. These data suggest
      that there is an urgent need to implement a national policy regulating the use of
      antibiotics, notably in the community, in order to limit the widespread increase
      in antimicrobial resistance.

PMID- 27873726
TI  - In vitro activity of tigecycline and comparators against carbapenem-resistant
      Enterobacteriaceae in Africa-Middle East countries: TEST 2007-2012.
AB  - Multidrug-resistant (MDR) Enterobacteriaceae are an emerging concern for
      healthcare providers. Infections caused by MDR pathogens are associated with
      increased costs, length of hospital stay, and morbidity and mortality rates.
      Carbapenem-resistant Enterobacteriaceae (CRE) continue to increase, and
      infections with these organisms are observed worldwide not only as hospital
      acquired infections but also as community-acquired infections. Increasing
      antimicrobial resistance dictates the need for continued surveillance studies of
      common and MDR pathogens. The Tigecycline Evaluation Surveillance Trial (TEST)
      examined the susceptibility of pathogens isolated in Africa and the Middle East
      from 2007 to 2012. A total of 4155 Enterobacteriaceae isolates were evaluated to
      determine the in vitro activity and changes in resistance patterns for
      tigecycline and comparators. Carbapenem resistance was found in 191 (4.6%) of the
      isolates tested. Klebsiella pneumoniae was the most common CRE (64.9%), followed
      by Enterobacter cloacae (14.1%) and Escherichia coli (9.9%). Tigecycline MIC90
      values (minimum inhibitory concentration required to inhibit 90% of the isolates)
      were 2MUg/mL against all of these enteric species, with susceptibility rates of
      96.8%, 92.6% and 100%, respectively. Tigecycline had in vitro activity against
      CRE, with a 95.3% susceptibility rate.

PMID- 27873727
TI  - In vitro activity of ceftaroline tested against isolates from the Asia-Pacific
      region and South Africa (2011).
AB  - During 2011, 29 medical centres in eight Asia-Pacific countries and South Africa
      submitted a total of 3697 bacterial pathogens for surveillance testing, of which
      39.1% were from respiratory tract, 27.9% from skin and skin-structure, 19.2% from
      bloodstream, 5.1% from urinary tract and 8.7% from miscellaneous infection types.
      Meticillin-resistant Staphylococcus aureus (MRSA) constituted 38.9% of the 1114
      S. aureus. The MRSA rate was 53.5% for respiratory tract infections and 31.8% for
      skin and skin-structure infections. A total of 86.5% of S. aureus exhibited
      ceftaroline minimum inhibitory concentrations (MICs) at <=1MUg/mL. Ceftaroline
      (MIC90, 0.25MUg/mL) was eight-fold more active than ceftriaxone (MIC90, 2MUg/mL)
      against Streptococcus pneumoniae; erythromycin and clindamycin susceptibility
      were severely compromised. Against beta-haemolytic streptococci, ceftaroline and
      other beta-lactams were highly active, with MIC90 values at 0.03MUg/mL. The
      extended-spectrum beta-lactamase (ESBL) phenotype rate was 57.6% among
      Escherichia coli, 49.7% among Klebsiella pneumoniae and 23.7% among Klebsiella
      oxytoca. ESBL phenotype rates for E. coli ranged from a low of 8.3% in South
      Africa to a high of 77.9% in India. For K. pneumoniae, the ESBL phenotype rate
      ranged from 20.6% in Australia to 67.8% in India. Ceftaroline was active against
      non-ESBL-phenotype E. coli and K. pneumoniae (MIC90, 0.25MUg/mL) but was not
      active against ESBL-phenotype strains (MIC90, >32MUg/mL). Overall, ceftaroline
      demonstrated in vitro activity against pathogens isolated from various infection
      sites, including respiratory tract, bloodstream, and skin and skin-structure
      infections, across the monitored nations.

PMID- 27873728
TI  - Outbreaks of multidrug-resistant Acinetobacter baumannii strains in a Kenyan
      teaching hospital.
AB  - Acinetobacter baumannii is a serious nosocomial pathogen with a high propensity
      to cause outbreaks. Whilst outbreaks of A. baumannii have been reported in many
      regions worldwide, few data are available from East Africa. In this study, 25 A.
      baumannii isolates derived from a single institution located in Nairobi, Kenya,
      between September 2010 and September 2011 were examined. Antimicrobial
      susceptibility testing was performed by the disc diffusion method and the
      relatedness among the isolates was examined by pulsed-field gel electrophoresis,
      repetitive sequence-based PCR (rep-PCR) and multilocus sequence typing. The
      examined isolates clustered into three distinct groups. The most prevalent
      sequence type (ST) was ST110 (17 isolates), followed by ST92 (5 isolates) and
      ST109 (3 isolates). All isolates exhibited resistance to cefepime, ceftazidime,
      ticarcillin/clavulanic acid, cefotaxime/clavulanic acid, piperacillin/tazobactam,
      cefoxitin, ciprofloxacin, gentamicin, nitrofurantoin, fosfomycin trometamol,
      trimethoprim/sulfamethoxazole, amikacin, meropenem and imipenem, with the
      exception of four isolates. Two isolates belonging to ST92 and two isolates
      belonging to ST109 were susceptible to amikacin; one of these amikacin
      susceptible ST109 isolates was also susceptible to meropenem and imipenem. All
      isolates were positive for OXA 51-like and all carbapenem-resistant isolates were
      OXA-23 positive.

PMID- 27873729
TI  - Evaluation of the antimicrobial activity of daptomycin and linezolid against
      vancomycin-resistant Enterococcus spp. isolates in south India.
AB  - Vancomycin-resistant enterococci (VRE) have emerged as a major nosocomial
      pathogen. Alternatives for the treatment of infection with VRE include linezolid
      and daptomycin. Experience with these agents, especially daptomycin, is limited
      in India. The minimum inhibitory concentration of linezolid and daptomycin
      against 98 clinical isolates of VRE was tested by E-test. Daptomycin and
      linezolid showed good activity, with susceptibility rates of 93.9% and 96.9%,
      respectively.

PMID- 27873730
TI  - Evolutionary rescue of bacteria via horizontal gene transfer under a lethal beta
      lactam concentration.
AB  - beta-Lactams are a commonly used class of bactericidal antibiotics. The number of
      beta-lactam-resistant pathogens is constantly increasing in hospitals around the
      world. Interestingly, most of the beta-lactam-resistant bacteria carry mobile
      genetic elements, such as conjugative plasmids, that render the pathogen
      resistant. These elements mediate their own transfer from one bacterium to
      another, producing new resistant strains via horizontal gene transfer. Here we
      investigated whether it is possible that transfer of the resistance element from
      another bacterium may evolutionarily rescue a susceptible bacterium exposed to a
      lethal concentration of the beta-lactam ampicillin. Indeed, the rescuing occurs
      even at very high, clinically significant antibiotic levels, suggesting that
      pathogens may acquire the resistance 'on the fly' from commensal bacteria during
      treatment.

PMID- 27873732
TI  - Adopting Chennai declaration strategies in the prevention and control of the
      spread of multidrug-resistant hospital-acquired bacterial infections in Nigeria:
      A call to action.

PMID- 27873731
TI  - Carbapenem-resistant Acinetobacter baumannii in the Republic of Belarus.

PMID- 27873733
TI  - Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four
      case reports and a review.
AB  - Until recently, food allergies to mammalian meats have been considered to be very
      rare. The observation that patients not previously exposed to the monoclonal
      chimeric antibody cetuximab suffered from severe anaphylaxis upon first exposure,
      led to the identification of galactose-alpha-1,3-galactose as a new relevant
      carbohydrate allergen. These patients later often suffered from anaphylactic
      reactions to red meat. Epidemiological data indicated that bites by the tick
      Amblyomma americanum in the USA, later also by Ixodes species in other
      continents, resulted in sensitisation to alpha-gal. On the other hand, in African
      patients with parasitic disorders, a high prevalence of anti-alpha-gal IgE,
      without clinical relevance, has been reported. In our four cases, one patient
      with a late onset of meat allergy had a history of a tick bite. The other three
      patients had symptoms from childhood or at a juvenile age. This indicates that in
      some patients, other ways of sensitisation may also take place. However, in
      patients without atopy, tick bite-induced IgE to alpha-gal may be more relevant.
      Diagnosis is based on a history of delayed onset of anaphylaxis. Skin tests with
      commercially available meat test solutions are often equivocal or negative; skin
      tests with raw meat and particularly pork kidney are more sensitive.
      Determination of specific IgE to alpha-gal is commercially available. The highest
      sensitivity is observed with skin and basophil activation tests with cetuximab
      which is, however, limited by its high costs.

PMID- 27873734
TI  - Generalized annular elastolytic giant cell granuloma successfully treated with
      the long-term use of minocycline hydrochloride.

PMID- 27873735
TI  - Long-term survival of a patient with metastatic melanoma treated with nivolumab
      and vemurafenib, with the development of vitiligo.

PMID- 27873736
TI  - Amber necklaces: reasons for use and awareness of risk associated with bacterial
      colonisation.
AB  - Parents are increasingly placing amber necklaces on their infants or toddlers to
      prevent teething pain. The use of the necklaces can pose a risk of death by
      strangulation, however, there are no data on the potential infectious risk linked
      to bacterial colonisation associated with the necklaces. We aimed to analyse
      bacterial colonisation of amber necklaces worn by children during hospital
      consultations. This prospective observational study included all children wearing
      a teething necklace at consultation in the Paediatric Dermatology and the
      Paediatric Emergency Department of our hospital from April to December 2014. The
      study included 27 children (median age: 10.7 months; 70.4% female). The surface
      of necklaces underwent bacteriological analyses using three different agar
      cultures. Parents completed a brief questionnaire to provide reasons for using
      necklaces and express awareness of risks. One child had a history of impetigo.
      All necklaces were colonised by bacteria (median: four species per necklace
      [range: 1-9]); 32 different species were found, the most frequent being coagulase
      negative staphylococci (Staphylococcus epidermidis in 88.9% of cases). In three
      cases, methicillin-sensitive Staphylococcus aureus was found. The most frequent
      reason for wearing a necklace was to prevent teething pain (n = 17; 63.0%); the
      necklace was judged effective (moderately/highly effective) in 74.1% of cases,
      however, 70.4% of parents considered the use of the necklace to be risky. Amber
      necklaces may be highly colonised by commensal germs of the skin, mainly
      coagulase-negative staphylococci. Although these bacteria are saprophytes, they
      may become pathogenic in particular conditions.

PMID- 27873737
TI  - Erythroderma and non-Hodgkin T-cell lymphoma: what else, apart from Mycosis
      Fungoides and Sezary syndrome?
AB  - BACKGROUND: Peripheral T-cell lymphomas, not otherwise specified (PTCL-NOS), are
      a rare condition characterised by specific histology, nodal presentation, and a
      poor prognosis. In total, 10-18% of patients present with cutaneous involvement
      which is regarded as a poor prognostic marker. However, cutaneous PTCL-NOS
      lesions have been rarely reported in the literature. OBJECTIVES: We sought to
      describe PTCL-NOS cases characterised by erythrodermic dissemination to the skin.
      MATERIALS & METHODS: Three cases of PTCL-NOS were investigated; all male, with a
      mean and median age of 55 and 51 years, respectively. RESULTS: All patients
      underwent aggressive chemotherapeutic protocols with only transient improvement
      of the disease, and died within two years of follow-up. CONCLUSION:
      Dermatologists should be reminded that erythroderma and lymph node enlargement do
      not represent an exclusive paradigm for erythrodermic cutaneous T-cell lymphoma,
      and that these features can be due to a systemic lymphoma that should be
      considered in the differential diagnosis.

PMID- 27873738
TI  - Sensitive skin and the influence of female hormone fluctuations: results from a
      cross-sectional digital survey in the Dutch population.
AB  - Sensitive skin is a widespread condition, which is most frequently reported by
      women. Changing hormone levels during the menstrual cycle and menopause have been
      suggested among the stimuli triggering sensitive skin. To investigate the
      perceived influence of fluctuating hormone levels on self-assessed sensitive
      skin, including symptoms and stimuli linked to skin sensitivity, as well as
      potential changes in facial and body skin and sensitive body parts, depending on
      hormonal status. A digital questionnaire was distributed to a population of women
      aged 20-65 years old. A total of 278 women were included in the analysis. About
      42% premenopausal women declared a perception of (increased) skin sensitivity
      just before and during the menstrual cycle, while this was reported by almost 32%
      of peri- and postmenopausal women following the menopause. The majority of
      reported symptoms included the presence of bumps/pimples, dryness, itching, and
      redness, and the majority of reported stimuli were shaving, weather, toiletries,
      and emotions. No differences emerged regarding characteristics of facial and body
      skin across different hormonal status. Significant differences in sensitivity of
      body parts emerged for the face and feet, reported by a larger percentage of
      premenopausal women and peri- and postmenopausal women, respectively. The
      prevalence of the perceived effects of fluctuating hormone levels on self
      assessed sensitive skin in women is high. These effects should be taken into
      consideration in skin testing and dermatological practice, and support the need
      for selecting personal care routine or treatment during the menstrual cycle and
      menopause.

PMID- 27873739
TI  - Red Blood Cell Transfusions in Greece: Results of a Survey of Red Blood Cell Use
      in 2013.
AB  - OBJECTIVE: Greece is ranked as the second highest consumer of blood components in
      Europe. For an effective transfusion system and in order to reduce variability of
      transfusion practice by implementing evidence-based transfusion guidelines it is
      necessary to study and monitor blood management strategies. Our study was
      conducted in order to evaluate the use of red blood cell units (RBC-U) in
      nationwide scale mapping parameters that contribute to their proper management in
      Greece. MATERIALS AND METHODS: The survey was conducted by the Working Committee
      of Transfusion Medicine&Apheresis of the Hellenic Society of Hematology from
      January to December 2013. The collected data included the number, ABO/D blood
      group, patients' department, and storage age of RBC-U transfused. RESULTS: The
      number of RBC-U evaluated was 103,702 (17.77%) out of 583,457 RBC-U transfused in
      Greece in 2013. RBC-U transfused by hospital department (mean percentage) was as
      follows: Surgery 29.34%, Internal Medicine 29.48%, Oncology/Hematology 14.65%,
      Thalassemia 8.87%, Intensive Care Unit 6.55%, Nephrology 1.78%,
      Obstetrics/Gynecology 1.46%, Neonatal&Pediatric 0.31%, Private Hospitals 8.57%.
      RBC-U distribution according to ABO/D blood group was: A: 39.02%, B: 12.41%, AB:
      5.16%, O: 43.41%, D+: 87.99%, D-: 12.01%. The majority of RBC-U (62.46%) was
      transfused in the first 15 days of storage, 25.24% at 16 to 28 days, and 12.28%
      at 29-42 days. CONCLUSION: Despite a high intercenter variability in RBC
      transfusions, surgical and internal medicine patients were the most common groups
      of patients transfused with an increasing rate for internal medicine patients.
      The majority of RBC-U were transfused within the first 15 days of storage, which
      is possibly the consequence of blood supply insufficiency leading to the direct
      use of fresh blood. Benchmarking transfusion activity may help to decrease the
      inappropriate use of blood products, reduce the cost of care, and optimize the
      use of the voluntary donor's gift.

PMID- 27873740
TI  - Response to Anastrozole Treatment in a Case with Peutz-Jeghers Syndrome and a
      Large Cell Calcifying Sertoli Cell Tumor.
AB  - Peutz-Jeghers syndrome (PJS) is inherited as an autosomal dominant trait
      characterized by multiple gastrointestinal hamartomatous polyps, mucocutaneous
      pigmentation, and an increased risk of neoplasm. Large-cell calcifying Sertoli
      cell tumor (LCCSCT) is a kind of sex cord-stromal tumor which may co-exist with
      PJS and which is characterized radiologically by calcification foci within the
      testes. Surgical treatment options for this tumor range from testis-preserving
      surgery to radical orchiectomy. Not with standing this invasive approach,
      recently, there are some case reports demonstrating the efficacy of aromatase
      inhibitors in avoiding orchiectomy and its associated complications. In this
      paper, we have presented a LCCSCT case diagnosed in a boy with PJS and his
      response to anastrozole treatment.

PMID- 27873741
TI  - Sole Infrequent Karyotypic Aberration Trisomy 6 in a Patient with Acute Myeloid
      Leukemia and Breast Cancer in Remission.

PMID- 27873742
TI  - Pachymeningeal Involvement with Blindness as the Presenting Manifestation of Non
      Hodgkin Lymphoma.

PMID- 27873743
TI  - Aneurysmal wall imaging in a case of cortical superficial siderosis and multiple
      unruptured aneurysms.
AB  - We report a case of interhemispheric and bifrontal cortical superficial siderosis
      in association with two intracranial aneurysms. The patient had no clinical
      history suggestive of aneurysm rupture, no feature of amyloid angiopathy or other
      apparent etiology for cortical siderosis. We performed high resolution brain MRI
      with dark blood T1 sequences before and after IV contrast injection. An anterior
      communicating aneurysm showed partial wall enhancement on the posterior wall
      whereas a left posterior communicating aneurysm did not. In the light of recent
      reports of the association of wall enhancement with unstable aneurysms, we
      considered wall enhancement to be a marker of inflammation and remodeling of the
      aneurysm wall, resulting in chronic hemorrhagic suffusion in the subarachnoid
      spaces. To our knowledge, this is the first report offering proof for a possible
      link between apparently unruptured aneurysms and cortical siderosis.

PMID- 27873744
TI  - Q fever hepatitis and endocarditis in the context of haemochromatosis.
AB  - Hereditary haemochromatosis is associated with increased susceptibility to some
      infections. We report here a case of Q fever in a patient with coexistent
      haemochromatosis. The literature is reviewed in regard to the effect of
      haemochromatosis on susceptibility to infectious disease in general and Q fever
      in particular. Although there is documented increased risk in these patients for
      some infectious conditions, a specific association with Q fever has not been
      previously reported. The present report raises the possibility of such a
      clinically relevant connection.

PMID- 27873745
TI  - Life-threatening Wunderlich's syndrome with concurrent clopidogrel use.
AB  - Spontaneous non-traumatic renal haemorrhage, or Wunderlich's syndrome, is a rare
      but potentially life-threatening event. We present the case of a 63-year-old man
      on clopidogrel who became haemodynamically unstable as a result of this
      condition. Angioembolisation revealed the unusual finding of active bleeding from
      multiple distinct subsegmental renal vessels, for which haemostasis was
      successfully achieved by coil placement. The patient remains well and with near
      normal renal function on follow-up.

PMID- 27873746
TI  - Acute aortic dissection in postpartum.

PMID- 27873747
TI  - Atypical presentation of appendicitis.
AB  - A woman aged 64 years presented as an emergency with a mass in the right iliac
      fossa, clinically within the abdominal wall, but an otherwise soft abdomen.
      Systemically, she was quite well with normal vital signs. Blood tests revealed
      raised inflammatory markers, and an abdominal CT scan demonstrated a perforated
      appendix with associated large subcutaneous abscess. This represents a rare
      presentation of a common condition, demonstrating how appendicitis can still be a
      challenging problem for the clinician. The patient underwent incision and
      drainage of the abscess, resulting in the formation of an enterocutaneous fistula
      (ECF). This was managed with enteral nutritional support, wound dressings and
      antibiotics. Following normal CT imaging, an ileocaecal resection was planned in
      the expectation that the ECF would persist. The operation was postponed due to
      intercurrent illness, during which time her symptoms and the ECF fully resolved.

PMID- 27873748
TI  - Intracranial venous thrombosis in a man taking clomiphene citrate.
AB  - Clomiphene citrate is widely used by the female population for the management of
      a wide array of medical conditions especially those related to ovulation, but its
      use in male population remains controversial. Efficacy of clomiphene is not well
      established in male hypogonadism and infertility. Its side effects and
      complications are also poorly studied or reported. We present a case of a man
      with infertility issues for which he started receiving clomiphene citrate 3 weeks
      before presenting with progressive symptoms of headache, vomiting, transient
      blurred vision and diplopia, which eventually turned out to be the symptoms of
      intracranial venous thrombosis. After excluding the common causes of intracranial
      venous thrombosis and hypercoagulable state, clomiphene citrate seems the most
      likely culprit.

PMID- 27873749
TI  - Neurosarcoidosis presenting as a large dural mass lesion.

PMID- 27873752
TI  - Hibernoma: diagnostic and surgical considerations of a rare benign tumour.
AB  - Hibernoma is a rare, benign tumour of brown fat origin. Less than 250 cases have
      been reported in the literature. We present a case of a 19-year-old man referred
      to surgical oncology for evaluation of a large soft tissue mass near the apex of
      his right scapula. Complete surgical excision was performed, sparing the
      overlying latissimus dorsi musculature. Surgical pathology revealed findings were
      consistent with hibernoma, grossly showing a well-encapsulated fluctuant mass
      measuring 21.4*14.4*5.3 cm, and histologically composed of brown fat adipocytes.
      The mainstay of treatment is surgical excision of the mass. Primary goals of the
      operation include complete removal of the mass to prevent recurrence and sparing
      of adjacent structures as it is a benign, non-invasive tumour. We present a case
      of a large chest wall hibernoma in a young adult, diagnosed on final pathology
      after complete surgical excision.

PMID- 27873750
TI  - Persistent spontaneous fungal peritonitis secondary to Candida albicans in a
      patient with alcoholic cirrhosis and review of the literature.
AB  - Candida albicans is a common human pathogen. Occasionally, it can cause
      peritonitis in immunocompromised and postsurgical patients. We report a case of a
      male patient who presented with abdominal pain and distention. He had a history
      of end-stage liver disease secondary to alcoholism. His peritoneal fluid culture
      revealed C albicans, and (1-3)-beta-d glucan (BDG) level was elevated. His
      hospital course was complicated by sepsis and renal failure. He was treated with
      antifungals for spontaneous fungal peritonitis. Fungal peritonitis should be
      suspected in patients with chronic liver disease particularly with elevated BDG
      levels.

PMID- 27873751
TI  - Rheumatoid vasculitis: early presentation of rheumatoid arthritis.
AB  - Rheumatoid vasculitis is a rare and late complication of rheumatoid arthritis and
      may affect small-to-medium-sized vessels. Here, we report a case of a 49-year-old
      man who presented with amaurosis fugax in the left eye, symmetric polyarthritis,
      Raynaud's symptoms and paraesthesia in both lower extremities. The patient
      subsequently experienced right foot drop, nail fold infracts and gangrene of his
      right second toe. He was found to have a high titre of rheumatoid factor and
      treatment with rituximab and high dose of corticosteroids led to significant
      improvement of his symptoms. This is rare case describing the early onset of
      rheumatoid vasculitis in a patient with rheumatoid arthritis.

PMID- 27873753
TI  - Primary Mycobacterium tuberculosis infection over insulin injection site.

PMID- 27873755
TI  - The DNA-based diet.

PMID- 27873754
TI  - Addressing the limitations of the CDC guideline for prescribing opioids for
      chronic noncancer pain.

PMID- 27873756
TI  - Infantile acne.

PMID- 27873757
TI  - Russia targets dissidents with punitive psychiatry.

PMID- 27873758
TI  - Seniors and self-harm factor in the opioid crisis.

PMID- 27873759
TI  - The curious career of Dr. Monica Kidd.

PMID- 27873760
TI  - Multimodality imaging in Bertolotti's syndrome: an important cause of low back
      pain in young adults.

PMID- 27873761
TI  - Hereditary angioedema (HAE): a cause for recurrent abdominal pain.
AB  - A 44-year-old Hispanic woman presented to the emergency room with a 2-day history
      of sudden onset of severe cramping left lower quadrant abdominal pain associated
      with ~20 episodes diarrhoea. Abdominal CT scan exhibited bowel wall oedema and
      acute extensive colitis. On the basis of the preliminary diagnosis of acute
      abdomen, the patient was admitted under the surgical team and treated for acute
      colitis. Since her family history was significant for hereditary angioedema
      (HAE), complement studies were performed which revealed low complement C4 levels
      and abnormally low values of C1q esterase inhibitor. Thus, the diagnosis of HAE
      type I was established. This case report summarises that the symptoms of HAE are
      often non-specific, hence making the underlying cause difficult to diagnose.

PMID- 27873762
TI  - Ganglioneuroma of the pancreas in a 4-year-old girl.
AB  - Ganglioneuroma (GN) is the uncommon, benign representative of the peripheral
      neuroblastic tumours (PNTs), which arise from primitive sympathetic ganglion
      cells. PNTs comprise one of the most common groups of neoplastic diseases in
      infants and children, but its occurrence in the pancreas is rare. We report a 4
      year-old girl with GN of the pancreas requiring pancreaticoduodenectomy as a
      definitive therapy and with a great outcome, and we review the published
      literature.

PMID- 27873763
TI  - Pericardiectomy as a diagnostic and therapeutic procedure.
AB  - A 70-year-old man presented with recent onset, predominantly right-sided heart
      failure. Echocardiogram demonstrated features of hypertensive heart disease and
      was suggestive of, but non-diagnostic for, constrictive pericarditis (CP). CT
      demonstrated mild pericardial thickening. Right heart catheterisation showed
      elevation and equalisation of diastolic pressures in all cardiac chambers with
      early rapid filling, minimal ventricular interdependence, and no dissociation of
      intrathoracic and intracardiac pressures. While several features pointed towards
      CP, the minimal ventricular interdependence and no dissociation of intrathoracic
      and intracardiac pressures suggested other pathology. Diagnostic pericardiectomy
      was performed, after which the central venous pressure decreased from 22 to 12 mm
      Hg. Pathology revealed pericardial fibrosis. The patient experienced sustained
      resolution of his heart failure. A potential explanation for lack of CP criteria
      was the presence of hypertensive heart disease. CP needs to be considered when
      approaching patients with heart failure as diagnostic evaluation can be
      multifaceted and treatment curative.

PMID- 27873764
TI  - Medial rectus muscle cysticercosis: an assessment using ultrasonography and CT.

PMID- 27873765
TI  - Extensive biatrial thrombus straddling the patent foramen ovale and traversing
      into the left and right ventricle.
AB  - We report an extremely rare case of an extensive biatrial thrombus straddling a
      patent foramen ovale (PFO) extending into the bilateral ventricles in a patient
      presenting with an acute embolic stroke. Our patient further developed a massive
      saddle pulmonary embolus (PE) with haemodynamic instability during the course of
      his hospitalisation. The risks of pharmacological thrombolysis or surgical
      thrombectomy for PE in a haemodynamically unstable patient with recent embolic
      stroke posed a significant therapeutic dilemma. Ultimately, the decision was made
      to continue anticoagulation with unfractionated heparin followed by oral
      Coumadin. The patient responded well to therapy and at 1-month follow-up, a
      complete resolution of the thrombus was documented on transoesophageal
      echocardiogram with full clinical recovery of the patient.

PMID- 27873766
TI  - Incidental finding of giant pericardial lipoma.
AB  - We describe a patient with an incidental finding of a large mass adjacent to the
      heart detected on a screening CT scan. The differential diagnosis included
      primary and secondary tumours of the heart. Subsequent investigation with trans
      thoracic echocardiogram and cardiac MRI confirmed a diagnosis of a giant
      pericardial lipoma, one of the common benign primary cardiac tumours.

PMID- 27873767
TI  - High-pressure studies with x-rays using diamond anvil cells.
AB  - Pressure profoundly alters all states of matter. The symbiotic development of
      ultrahigh-pressure diamond anvil cells, to compress samples to sustainable multi
      megabar pressures; and synchrotron x-ray techniques, to probe materials'
      properties in situ, has enabled the exploration of rich high-pressure (HP)
      science. In this article, we first introduce the essential concept of diamond
      anvil cell technology, together with recent developments and its integration with
      other extreme environments. We then provide an overview of the latest
      developments in HP synchrotron techniques, their applications, and current
      problems, followed by a discussion of HP scientific studies using x-rays in the
      key multidisciplinary fields. These HP studies include: HP x-ray emission
      spectroscopy, which provides information on the filled electronic states of HP
      samples; HP x-ray Raman spectroscopy, which probes the HP chemical bonding
      changes of light elements; HP electronic inelastic x-ray scattering spectroscopy,
      which accesses high energy electronic phenomena, including electronic band
      structure, Fermi surface, excitons, plasmons, and their dispersions; HP resonant
      inelastic x-ray scattering spectroscopy, which probes shallow core excitations,
      multiplet structures, and spin-resolved electronic structure; HP nuclear resonant
      x-ray spectroscopy, which provides phonon densities of state and time-resolved
      Mossbauer information; HP x-ray imaging, which provides information on
      hierarchical structures, dynamic processes, and internal strains; HP x-ray
      diffraction, which determines the fundamental structures and densities of single
      crystal, polycrystalline, nanocrystalline, and non-crystalline materials; and HP
      radial x-ray diffraction, which yields deviatoric, elastic and rheological
      information. Integrating these tools with hydrostatic or uniaxial pressure media,
      laser and resistive heating, and cryogenic cooling, has enabled investigations of
      the structural, vibrational, electronic, and magnetic properties of materials
      over a wide range of pressure-temperature conditions.

PMID- 27873768
TI  - Sexual dysfunction and prostate cancer risk: one more piece of a complex puzzle.

PMID- 27873770
TI  - Coordinate cis-[Cr(C2O4)(pm)(OH2)2]+ Cation as Molecular Biosensor of Pyruvate's
      Protective Activity Against Hydrogen Peroxide Mediated Cytotoxity.
AB  - In this paper instrumental methods of carbon dioxide (CO2) detection in
      biological material were compared. Using cis-[Cr(C2O4)(pm)(OH2)2]+ cation as a
      specific molecular biosensor and the stopped-flow technique the concentrations of
      CO2 released from the cell culture medium as one of final products of pyruvate
      decomposition caused by hydrogen peroxide were determined. To prove the
      usefulness of our method of CO2 assessment in the case of biological samples we
      investigated protective properties of exogenous pyruvate in cultured osteosarcoma
      143B cells exposed to 1 mM hydrogen peroxide (H2O2) added directly to culture
      medium. Pyruvic acid is well known scavenger of H2O2 and, moreover, a molecule
      which is recognized as one of the major mediator of oxidative stress detected in
      many diseases and pathological situations like ischemiareperfusion states. The
      pyruvate's antioxidant activity is described as its rapid reaction with
      H2O2,which causes nonenzymatic decarboxylation of pyruvate and releases of CO2,
      water and acetate as final products. In this work for the first time we have
      correlated the concentration of CO2 dissolved in culture medium with pyruvate's
      oxidant-scavenging abilities. Moreover, the kinetics of the reaction between
      aqueous solution of CO2 and coordinate ion, cis-[Cr(C2O4)(pm)(OH2)2]+ was
      analysed. The results obtained enabled determination of the number of steps of
      the reaction studied. Based on the kinetic equations, rate constants were
      determined for each step.

PMID- 27873771
TI  - Object-Based Point Cloud Analysis of Full-Waveform Airborne Laser Scanning Data
      for Urban Vegetation Classification.
AB  - Airborne laser scanning (ALS) is a remote sensing technique well-suited for 3D
      vegetation mapping and structure characterization because the emitted laser
      pulses are able to penetrate small gaps in the vegetation canopy. The
      backscattered echoes from the foliage, woody vegetation, the terrain, and other
      objects are detected, leading to a cloud of points. Higher echo densities (> 20
      echoes/m2) and additional classification variables from full-waveform (FWF) ALS
      data, namely echo amplitude, echo width and information on multiple echoes from
      one shot, offer new possibilities in classifying the ALS point cloud. Currently
      FWF sensor information is hardly used for classification purposes. This
      contribution presents an object-based point cloud analysis (OBPA) approach,
      combining segmentation and classification of the 3D FWF ALS points designed to
      detect tall vegetation in urban environments. The definition tall vegetation
      includes trees and shrubs, but excludes grassland and herbage. In the applied
      procedure FWF ALS echoes are segmented by a seeded region growing procedure. All
      echoes sorted descending by their surface roughness are used as seed points.
      Segments are grown based on echo width homogeneity. Next, segment statistics
      (mean, standard deviation, and coefficient of variation) are calculated by
      aggregating echo features such as amplitude and surface roughness. For
      classification a rule base is derived automatically from a training area using a
      statistical classification tree. To demonstrate our method we present data of
      three sites with around 500,000 echoes each. The accuracy of the classified
      vegetation segments is evaluated for two independent validation sites. In a point
      wise error assessment, where the classification is compared with manually
      classified 3D points, completeness and correctness better than 90% are reached
      for the validation sites. In comparison to many other algorithms the proposed 3D
      point classification works on the original measurements directly, i.e. the
      acquired points. Gridding of the data is not necessary, a process which is
      inherently coupled to loss of data and precision. The 3D properties provide
      especially a good separability of buildings and terrain points respectively, if
      they are occluded by vegetation.

PMID- 27873772
TI  - An Energy-Efficient and High-Quality Video Transmission Architecture in Wireless
      Video-Based Sensor Networks.
AB  - Technological progress in the fields of Micro Electro-Mechanical Systems (MEMS)
      and wireless communications and also the availability of CMOS cameras,
      microphones and small-scale array sensors, which may ubiquitously capture
      multimedia content from the field, have fostered the development of low-cost
      limited resources Wireless Video-based Sensor Networks (WVSN). With regards to
      the constraints of videobased sensor nodes and wireless sensor networks, a
      supporting video stream is not easy to implement with the present sensor network
      protocols. In this paper, a thorough architecture is presented for video
      transmission over WVSN called Energy-efficient and high-Quality Video
      transmission Architecture (EQV-Architecture). This architecture influences three
      layers of communication protocol stack and considers wireless video sensor nodes
      constraints like limited process and energy resources while video quality is
      preserved in the receiver side. Application, transport, and network layers are
      the layers in which the compression protocol, transport protocol, and routing
      protocol are proposed respectively, also a dropping scheme is presented in
      network layer. Simulation results over various environments with dissimilar
      conditions revealed the effectiveness of the architecture in improving the
      lifetime of the network as well as preserving the video quality.

PMID- 27873769
TI  - Androgen receptor gene CAG and GGN repeat lengths as predictors of recovery of
      spermatogenesis following testicular germ cell cancer treatment.
AB  - Spermatogenesis is an androgen-regulated process that depends on the action of
      androgen receptor (AR). Sperm production may be affected in men treated for
      testicular cancer (TC), and it is important to identify the factors influencing
      the timing of spermatogenesis recovery following cancer treatment. It is known
      that the CAG and GGN repeat numbers affect the activity of the AR; therefore, the
      aim of this study is to investigate if the CAG and GGN polymorphisms in the AR
      gene predict recovery of sperm production after TC treatment. TC patients (n =
      130) delivered ejaculates at the following time points: postorchiectomy and at 6,
      12, 24, 36, and 60 months posttherapy (T0, T6, T12, T24, T36, and T60). The CAG
      lengths were categorized into three groups, <22 CAG, 22-23 CAG, and >23 CAG, and
      the GGN tracts were also categorized into three groups, <23 GGN, 23 GGN, and >23
      GGN. At T12, men with 22-23 CAG presented with a statistically significantly (P =
      0.045) lower sperm concentration than those with other CAG numbers (8.4 * 106 ml
      1 vs 16 * 106 ml-1 ; 95% CI: 1.01-2.65). This association was robust to omitting
      adjustment for treatment type and sperm concentration at T0 (P = 0.021; 3.7 * 106
      ml-1 vs 10 * 106 ml-1 ; 95% CI: 1.13-4.90). The same trends were observed for
      total sperm number. The least active AR variant seems to be associated with a
      more rapid recovery of spermatogenesis. This finding adds to our understanding of
      the biology of postcancer therapy recovery of fertility in males and has clinical
      implications.

PMID- 27873773
TI  - Anodic Voltammetry of Thioacetamide and its Amperometric Determination in Aqueous
      Media.
AB  - TAA is a harmful, presumptive pollutant in tap waters and waste waters. Several
      alternatives have been tested as new possibilities for the anodic determination
      of TAA in aqueous solutions, simulated waste waters and tap water. The
      electrochemical behaviour of thioacetamide (TAA) was investigated at a boron
      doped diamond (BDD) electrode both in unbuffered 0.1 M Na2SO4 and buffered
      solutions as supporting electrolytes. The anodic oxidation of TAA showed well
      defined limiting currents or current peaks and a good linearity of the
      amperometric signal vs. concentration plots. The analytical parameters of
      sensitivity, RSD and LOD, obtained under various experimental conditions, suggest
      the suitability of the BDD electrode for electroanalytical purposes. Low fouling
      effects, good reproducibility and stability, as well as the sharpness of the
      amperometric signals in both unbuffered/ buffered acidic or neutral media, highly
      superior to those obtained using a glassy carbon (GC) electrode, recommend the
      unmodified BDD electrode as a promising potential amperometric sensor for
      environmental applications, regarding the direct anodic determination of TAA in
      aqueous media.

PMID- 27873774
TI  - Water Quality Monitoring for Lake Constance with a Physically Based Algorithm for
      MERIS Data.
AB  - A physically based algorithm is used for automatic processing of MERIS level 1B
      full resolution data. The algorithm is originally used with input variables for
      optimization with different sensors (i.e. channel recalibration and weighting),
      aquatic regions (i.e. specific inherent optical properties) or atmospheric
      conditions (i.e. aerosol models). For operational use, however, a lake-specific
      parameterization is required, representing an approximation of the spatio
      temporal variation in atmospheric and hydrooptic conditions, and accounting for
      sensor properties. The algorithm performs atmospheric correction with a LUT for
      at-sensor radiance, and a downhill simplex inversion of chl-a, sm and y from
      subsurface irradiance reflectance. These outputs are enhanced by a selective
      filter, which makes use of the retrieval residuals. Regular chl-a sampling
      measurements by the Lake's protection authority coinciding with MERIS
      acquisitions were used for parameterization, training and validation.

PMID- 27873775
TI  - Determination of Parathion and Carbaryl Pesticides in Water and Food Samples
      Using a Self Assembled Monolayer /Acetylcholinesterase Electrochemical Biosensor.
AB  - An acetylcholinesterase (AchE) based amperometric biosensor was developed by
      immobilisation of the enzyme onto a self assembled modified gold electrode.
      Cyclic voltammetric experiments performed with the SAM-AchE biosensor in
      phosphate buffer solutions (pH = 7.2) containing acetylthiocholine confirmed the
      formation of thiocholine and its electrochemical oxidation at Ep = 0.28 V vs
      Ag/AgCl. An indirect methodology involving the inhibition effect of parathion and
      carbaryl on the enzymatic reaction was developed and employed to measure both
      pesticides in spiked natural water and food samples without pre-treatment or pre
      concentration steps. Values higher than 91-98.0% in recovery experiments
      indicated the feasibility of the proposed electroanalytical methodology to
      quantify both pesticides in water or food samples. HPLC measurements were also
      performed for comparison and confirmed the values measured amperometrically.

PMID- 27873776
TI  - HF Radar Sea-echo from Shallow Water.
AB  - HF radar systems are widely and routinely used for the measurement of ocean
      surface currents and waves. Analysis methods presently in use are based on the
      assumption of infinite water depth, and may therefore be inadequate close to
      shore where the radar echo is strongest. In this paper, we treat the situation
      when the radar echo is returned from ocean waves that interact with the ocean
      floor. Simulations are described which demonstrate the effect of shallow water on
      radar sea-echo. These are used to investigate limits on the existing theory and
      to define water depths at which shallow-water effects become significant. The
      second-order spectral energy increases relative to the first-order as the water
      depth decreases, resulting in spectral saturation when the waveheight exceeds a
      limit defined by the radar transmit frequency. This effect is particularly marked
      for lower radar transmit frequencies. The saturation limit on waveheight is less
      for shallow water. Shallow water affects second-order spectra (which gives wave
      information) far more than first-order (which gives information on current
      velocities), the latter being significantly affected only for the lowest radar
      transmit frequencies for extremely shallow water. We describe analysis of radar
      echo from shallow water measured by a Rutgers University HF radar system to give
      ocean wave spectral estimates. Radar-derived wave height, period and direction
      are compared with simultaneous shallow-water in-situ measurements.

PMID- 27873777
TI  - Single Photon Avalanche Diodes: Towards the Large Bidimensional Arrays.
AB  - Single photon detection is one of the most challenging goals of photonics. In
      recent years, the study of ultra-fast and/or low-intensity phenomena has received
      renewed attention from the academic and industrial communities. Intense research
      activity has been focused on bio-imaging applications, bio-luminescence, bio
      scattering methods, and, more in general, on several applications requiring high
      speed operation and high timing resolution. In this paper we present design and
      characterization of bi-dimensional arrays of a next generation of single photon
      avalanche diodes (SPADs). Single photon sensitivity, dark noise, afterpulsing and
      timing resolution of the single SPAD have been examined in several experimental
      conditions. Moreover, the effects arising from their integration and the readout
      mode have also been deeply investigated.

PMID- 27873778
TI  - Performance and Transient Behavior of Vertically Integrated Thin-film Silicon
      Sensors.
AB  - Vertical integration of amorphous hydrogenated silicon diodes on CMOS readout
      chips offers several advantages compared to standard CMOS imagers in terms of
      sensitivity, dynamic range and dark current while at the same time introducing
      some undesired transient effects leading to image lag. Performance of such
      sensors is here reported and their transient behaviour is analysed and compared
      to the one of corresponding amorphous silicon test diodes deposited on glass. The
      measurements are further compared to simulations for a deeper investigation. The
      long time constant observed in dark or photocurrent decay is found to be rather
      independent of the density of defects present in the intrinsic layer of the
      amorphous silicon diode.

PMID- 27873780
TI  - Remote Sensing of Agro-droughts in Guangdong Province of China Using MODIS
      Satellite Data.
AB  - A practical approach was developed in the study for drought monitoring in
      Guangdong province of China on the basis of vegetation supply water index (VSWI)
      and precipitation distance index (PDI). A comprehensive index for assessment of
      agro-drought severity (SADI) was then established from the normalized VSWI and
      PDI. Using MODIS satellite images and precipitation data from ground-observed
      meteorological stations, we applied the approach to Guangdong for drought
      monitoring in 2006. The monitoring results showed that the drought severity on
      average was very low in the province during the main growing season from May to
      September in 2006. However, seasonal variation of the severity was also obvious
      in difference counties of the province. Higher severity of drought could be seen
      in the periods of late-June (In China each month is traditionally divided into 3
      periods. Each is with 10 days and has different names. This division system is
      mainly with consideration of farming seasons hence has been widely used as the
      basis of drought monitoring periods in China. In order to keep this tradition, we
      define, for example, for June, the early-June as the period from 1st to 10th of
      June, the mid-June as the period from 11th to 20th, and the late-June as the
      period from 21st to 30th. So mid-August denotes the period from 11th to 20th of
      August, and early-July the period from 1st to 10th of July, and so on.), early
      July, mid-August and late-September. Regionally, Leizhou Peninsula in the west
      had the most serious drought before mid-May. Validation indicated that our
      monitoring results were generally consistent with the drought statistics data and
      the results from Chinese National Satellite Meteorological Center (CNSMC), which
      used only remote sensing data. This consistence confirmed the applicability of
      our approach for drought monitoring. Our better identification of drought
      severity in Leizhou Peninsula of western Guangdong than that of CNSMC might
      suggest that the approach developed in the study was able to provide a better
      alternative to increase the accuracy of drought monitoring for agricultural
      administration and farming.

PMID- 27873781
TI  - Estimation of Tree Size Diversity Using Object Oriented Texture Analysis and
      Aster Imagery.
AB  - This study investigates the potential of object-based texture parameters
      extracted from 15m spatial resolution ASTER imagery for estimating tree size
      diversity in a Mediterranean forested landscape in Turkey. Tree size diversity
      based on tree basal area was determined using the Shannon index and Gini
      Coefficient at the sampling plot level. Image texture parameters were calculated
      based on the grey level co-occurrence matrix (GLCM) for various image
      segmentation levels. Analyses of relationships between tree size diversity and
      texture parameters found that relationships between the Gini Coefficient and the
      GLCM values were the most statistically significant, with the highest correlation
      (r=0.69) being with GLCM Homogeneity values. In contrast, Shannon Index values
      were weakly correlated with image derived texture parameters. The results suggest
      that 15m resolution Aster imagery has considerable potential in estimating tree
      size diversity based on the Gini Coefficient for heterogeneous Mediterranean
      forests.

PMID- 27873779
TI  - Antibody Fragments as Probe in Biosensor Development.
AB  - Today's proteomic analyses are generating increasing numbers of biomarkers,
      making it essential to possess highly specific probes able to recognize those
      targets. Antibodies are considered to be the first choice as molecular
      recognition units due to their target specificity and affinity, which make them
      excellent probes in biosensor development. However several problems such as
      difficult directional immobilization, unstable behavior, loss of specificity and
      steric hindrance, may arise from using these large molecules. Luckily, protein
      engineering techniques offer designed antibody formats suitable for biomarker
      analysis. Minimization strategies of antibodies into Fab fragments, scFv or even
      single-domain antibody fragments like VH, VL or VHHs are reviewed. Not only the
      size of the probe but also other issues like choice of immobilization tag, type
      of solid support and probe stability are of critical importance in assay
      development for biosensing. In this respect, multiple approaches to specifically
      orient and couple antibody fragments in a generic one-step procedure directly on
      a biosensor substrate are discussed.

PMID- 27873782
TI  - Detecting Land Subsidence in Shanghai by PS-Networking SAR Interferometry.
AB  - Existing studies have shown that satellite synthetic aperture radar (SAR)
      interferometry has two apparent drawbacks, i.e., temporal decorrelation and
      atmospheric contamination, in the application of deformation mapping. It is
      however possible to improve deformation analysis by tracking some natural or man
      made objects with steady radar reflectivity, i.e., permanent scatterers (PS), in
      the frame of time series of SAR images acquired over the same area. For detecting
      land subsidence in Shanghai, China, this paper presents an attempt to explore an
      approach of PS-neighborhood networking SAR interferometry. With use of 26 ERS-1/2
      SAR images acquired 1992 through 2002 over Shanghai, the analysis of subsiding
      process in time and space is performed on the basis of a strong network which is
      formed by connecting neighboring PSs according to a distance threshold. The
      linear and nonlinear subsidence, atmospheric effects as well as topographic
      errors can be separated effectively in this way. The subsidence velocity field in
      10 years over Shanghai is also derived. It was found that the annual subsidence
      rates in the study area range from -2.1 to -0.6 cm/yr, and the averaged
      subsidence rate reaches -1.1 cm/yr.

PMID- 27873783
TI  - Geodetic Network Design and Optimization on the Active Tuzla Fault (Izmir,
      Turkey) for Disaster Management.
AB  - Both seismological and geodynamic research emphasize that the Aegean Region,
      which comprises the Hellenic Arc, the Greek mainland and Western Turkey is the
      most seismically active region in Western Eurasia. The convergence of the
      Eurasian and African lithospheric plates forces a westward motion on the
      Anatolian plate relative to the Eurasian one. Western Anatolia is a valuable
      laboratory for Earth Science research because of its complex geological
      structure. Izmir is a large city in Turkey with a population of about 2.5 million
      that is at great risk from big earthquakes. Unfortunately, previous geodynamics
      studies performed in this region are insufficient or cover large areas instead of
      specific faults. The Tuzla Fault, which is aligned trending NE-SW between the
      town of Menderes and Cape Doganbey, is an important fault in terms of seismic
      activity and its proximity to the city of Izmir. This study aims to perform a
      large scale investigation focusing on the Tuzla Fault and its vicinity for better
      understanding of the region's tectonics. In order to investigate the crustal
      deformation along the Tuzla Fault and Izmir Bay, a geodetic network has been
      designed and optimizations were performed. This paper suggests a schedule for a
      crustal deformation monitoring study which includes research on the tectonics of
      the region, network design and optimization strategies, theory and practice of
      processing. The study is also open for extension in terms of monitoring different
      types of fault characteristics. A one-dimensional fault model with two parameters
      - standard strike-slip model of dislocation theory in an elastic half-space - is
      formulated in order to determine which sites are suitable for the campaign based
      geodetic GPS measurements. Geodetic results can be used as a background data for
      disaster management systems.

PMID- 27873784
TI  - Feature Reduction in Graph Analysis.
AB  - A common approach to improve medical image classification is to add more features
      to the classifiers; however, this increases the time required for preprocessing
      raw data and training the classifiers, and the increase in features is not always
      beneficial. The number of commonly used features in the literature for training
      of image feature classifiers is over 50. Existing algorithms for selecting a
      subset of available features for image analysis fail to adequately eliminate
      redundant features. This paper presents a new selection algorithm based on graph
      analysis of interactions among features and between features to classifier
      decision. A modification of path analysis is done by applying regression
      analysis, multiple logistic and posterior Bayesian inference in order to
      eliminate features that provide the same contributions. A database of 113
      mammograms from the Mammographic Image Analysis Society was used in the
      experiments. Tested on two classifiers - ANN and logistic regression - cancer
      detection accuracy (true positive and false-positive rates) using a 13-feature
      set selected by our algorithm yielded substantially similar accuracy as using a
      26-feature set selected by SFS and results using all 50-features. However, the 13
      feature greatly reduced the amount of computation needed.

PMID- 27873785
TI  - CO2 Selective Potentiometric Sensor in Thick-film Technology.
AB  - A potentiometric sensor device based on screen-printed Nasicon films was
      investigated. In order to transfer the promising sensor concept of an open sodium
      titanate reference to thick film technology, "sodium-rich" and "sodium-poor"
      formulations were compared. While the "sodium-rich" composition was found to
      react with the ion conducting Nasicon during thermal treatment, the "sodium-poor"
      reference mixture was identified as an appropriate reference composition. Screen
      printed sensor devices were prepared and tested with respect to CO2 response,
      reproducibility, and cross-interference of oxygen. Excellent agreement with the
      theory was observed. With the integration of a screen-printed heater, sensor
      elements were operated actively heated in a cold gas stream.

PMID- 27873786
TI  - An Interactive Technique for Cartographic Feature Extraction from Aerial and
      Satellite Image Sensors.
AB  - In this paper, an interactive technique for extracting cartographic features from
      aerial and spatial images is presented. The method is essentially an interactive
      method of image region segmentation based on pixel grey level and texture
      information. The underlying segmentation method is seeded region growing. The
      criterion for growing regions is based on both texture and grey level, where
      texture is quantified using cooccurrence matrices. The Kullback distance is
      utilised with co-occurrence matrices in order to describe the image texture, then
      the Theory of Evidence is applied to merge the information coming from texture
      and grey level image from the RGB bands. Several results from aerial and spatial
      images that support the technique are presented.

PMID- 27873787
TI  - Modelling Amperometric Biosensors Based on Chemically Modified Electrodes.
AB  - The response of an amperometric biosensor based on a chemically modified
      electrode was modelled numerically. A mathematical model of the biosensor is
      based on a system of non-linear reaction-diffusion equations. The modelling
      biosensor comprises two compartments: an enzyme layer and an outer diffusion
      layer. In order to define the main governing parameters the corresponding
      dimensionless mathematical model was derived. The digital simulation was carried
      out using the finite difference technique. The adequacy of the model was
      evaluated using analytical solutions known for very specific cases of the model
      parameters. By changing model parameters the output results were numerically
      analyzed at transition and steady state conditions. The influence of the
      substrate and mediator concentrations as well as of the thicknesses of the enzyme
      and diffusion layers on the biosensor response was investigated. Calculations
      showed complex kinetics of the biosensor response, especially when the biosensor
      acts under a mixed limitation of the diffusion and the enzyme interaction with
      the substrate.

PMID- 27873788
TI  - Distributed Principal Component Analysis for Wireless Sensor Networks.
AB  - The Principal Component Analysis (PCA) is a data dimensionality reduction
      technique well-suited for processing data from sensor networks. It can be applied
      to tasks like compression, event detection, and event recognition. This technique
      is based on a linear transform where the sensor measurements are projected on a
      set of principal components. When sensor measurements are correlated, a small set
      of principal components can explain most of the measurements variability. This
      allows to significantly decrease the amount of radio communication and of energy
      consumption. In this paper, we show that the power iteration method can be
      distributed in a sensor network in order to compute an approximation of the
      principal components. The proposed implementation relies on an aggregation
      service, which has recently been shown to provide a suitable framework for
      distributing the computation of a linear transform within a sensor network. We
      also extend this previous work by providing a detailed analysis of the
      computational, memory, and communication costs involved. A compression experiment
      involving real data validates the algorithm and illustrates the tradeoffs between
      accuracy and communication costs.

PMID- 27873789
TI  - Using the Remote Sensing and GIS Technology for Erosion Risk Mapping of
      Kartalkaya Dam Watershed in Kahramanmaras, Turkey.
AB  - The soil erosion is the most serious environmental problem in watershed areas in
      Turkey. The main factors affecting the amount of soil erosion include vegetation
      cover, topography, soil, and climate. In order to describe the areas with high
      soil erosion risks and to develop adequate erosion prevention measures in the
      watersheds of dams, erosion risk maps should be generated considering these
      factors. Remote Sensing (RS) and Geographic Information System (GIS) technologies
      were used for erosion risk mapping in Kartalkaya Dam Watershed of Kahramanmaras,
      Turkey, based on the methodology implemented in COoRdination of INformation on
      the Environment (CORINE) model. ASTER imagery was used to generate a land
      use/cover classification in ERDAS Imagine. The digital maps of the other factors
      (topography, soil types, and climate) were generated in ArcGIS v9.2, and were
      then integrated as CORINE input files to produce erosion risk maps. The results
      indicate that 33.82%, 35.44%, and 30.74% of the study area were under low,
      moderate, and high actual erosion risks, respectively. The CORINE model
      integrated with RS and GIS technologies has great potential for producing
      accurate and inexpensive erosion risk maps in Turkey.

PMID- 27873790
TI  - A Fast Inspection of Tool Electrode and Drilling Depth in EDM Drilling by
      Detection Line Algorithm.
AB  - The purpose of this study was to develop a novel measurement method using a
      machine vision system. Besides using image processing techniques, the proposed
      system employs a detection line algorithm that detects the tool electrode length
      and drilling depth of a workpiece accurately and effectively. Different
      boundaries of areas on the tool electrode are defined: a baseline between base
      and normal areas, a ND-line between normal and drilling areas (accumulating
      carbon area), and a DD-line between drilling area and dielectric fluid droplet on
      the electrode tip. Accordingly, image processing techniques are employed to
      extract a tool electrode image, and the centroid, eigenvector, and principle axis
      of the tool electrode are determined. The developed detection line algorithm
      (DLA) is then used to detect the baseline, ND-line, and DD-line along the
      direction of the principle axis. Finally, the tool electrode length and drilling
      depth of the workpiece are estimated via detected baseline, ND-line, and DD-line.
      Experimental results show good accuracy and efficiency in estimation of the tool
      electrode length and drilling depth under different conditions. Hence, this
      research may provide a reference for industrial application in EDM drilling
      measurement.

PMID- 27873791
TI  - Estimation of Phytoplankton Responses to Hurricane Gonu over the Arabian Sea
      Based on Ocean Color Data.
AB  - In this study the authors investigated phytoplankton variations in the Arabian
      Sea associated with Hurricane Gonu using remote-sensing data of chlorophyll-a
      (Chl-a), sea surface temperature (SST) and winds. Additional data sets used for
      the study included the hurricane and Conductivity-Temperature-Depth data.
      Hurricane Gonu, presenting extremely powerful wind intensity, originated over the
      central Arabian Sea (near 67.7oE, 15.1oN) on June 2, 2007; it traveled along a
      northwestward direction and made landfall in Iran around June 7. Before Hurricane
      Gonu, Chl-a data indicated relatively low phytoplankton biomass (0.05-0.2 mg m
      3), along with generally high SST (>28.5 oC) and weak wind (.

PMID- 27873792
TI  - SAR Observation and Modeling of Gap Winds in the Prince William Sound of Alaska.
AB  - Alaska's Prince William Sound (PWS) is a unique locale tending to have strong gap
      winds, especially in the winter season. To characterize and understand these
      strong surface winds, which have great impacts on the local marine and aviation
      activities, the surface wind retrieval from the Synthetic Aperture Radar data
      (SAR-wind) is combined with a numerical mesoscale model. Helped with the SAR-wind
      observations, the mesoscale model is used to study cases of strong winds and
      relatively weak winds to depict the nature of these winds, including the area of
      extent and possible causes of the wind regimes. The gap winds from the Wells
      Passage and the Valdez Arm are the most dominant gap winds in PWS. Though the
      Valdez Arm is north-south trending and Wells Passage is east-west oriented, gap
      winds often develop simultaneously in these two places when a low pressure system
      is present in the Northern Gulf of Alaska. These two gap winds often converge at
      the center of PWS and extend further out of the Sound through the Hinchinbrook
      Entrance. The pressure gradients imposed over these areas are the main driving
      forces for these gap winds. Additionally, the drainage from the upper stream
      glaciers and the blocking effect of the banks of the Valdez Arm probably play an
      important role in enhancing the gap wind.

PMID- 27873793
TI  - Empirical Retrieval of Surface Melt Magnitude from Coupled MODIS Optical and
      Thermal Measurements over the Greenland Ice Sheet during the 2001 Ablation
      Season.
AB  - Accelerated ice flow near the equilibrium line of west-central Greenland Ice
      Sheet (GIS) has been attributed to an increase in infiltrated surface melt water
      as a response to climate warming. The assessment of surface melting events must
      be more than the detection of melt onset or extent. Retrieval of surface melt
      magnitude is necessary to improve understanding of ice sheet flow and surface
      melt coupling. In this paper, we report on a new technique to quantify the
      magnitude of surface melt. Cloud-free dates of June 10, July 5, 7, 9, and 11,
      2001 Moderate Resolution Imaging Spectroradiometer (MODIS) daily reflectance Band
      5 (1.230-1.250MUm) and surface temperature images rescaled to 1km over western
      Greenland were used in the retrieval algorithm. An optical-thermal feature space
      partitioned as a function of melt magnitude was derived using a one-dimensional
      thermal snowmelt model (SNTHERM89). SNTHERM89 was forced by hourly meteorological
      data from the Greenland Climate Network (GC-Net) at reference sites spanning dry
      snow, percolation, and wet snow zones in the Jakobshavn drainage basin in western
      GIS. Melt magnitude or effective melt (E-melt) was derived for satellite
      composite periods covering May, June, and July displaying low fractions (0-1%) at
      elevations greater than 2500m and fractions at or greater than 15% at elevations
      lower than 1000m assessed for only the upper 5 cm of the snow surface. Validation
      of E-melt involved comparison of intensity to dry and wet zones determined from
      QSCAT backscatter. Higher intensities (> 8%) were distributed in wet snow zones,
      while lower intensities were grouped in dry zones at a first order accuracy of ~
      +/-2%.

PMID- 27873794
TI  - Ship Detection in SAR Image Based on the Alpha-stable Distribution.
AB  - This paper describes an improved Constant False Alarm Rate (CFAR) ship detection
      algorithm in spaceborne synthetic aperture radar (SAR) image based on Alphastable
      distribution model. Typically, the CFAR algorithm uses the Gaussian distribution
      model to describe statistical characteristics of a SAR image background clutter.
      However, the Gaussian distribution is only valid for multilook SAR images when
      several radar looks are averaged. As sea clutter in SAR images shows spiky or
      heavy-tailed characteristics, the Gaussian distribution often fails to describe
      background sea clutter. In this study, we replace the Gaussian distribution with
      the Alpha-stable distribution, which is widely used in impulsive or spiky signal
      processing, to describe the background sea clutter in SAR images. In our proposed
      algorithm, an initial step for detecting possible ship targets is employed. Then,
      similar to the typical two-parameter CFAR algorithm, a local process is applied
      to the pixel identified as possible target. A RADARSAT-1 image is used to
      validate this Alpha-stable distribution based algorithm. Meanwhile, known ship
      location data during the time of RADARSAT-1 SAR image acquisition is used to
      validate ship detection results. Validation results show improvements of the new
      CFAR algorithm based on the Alpha-stable distribution over the CFAR algorithm
      based on the Gaussian distribution.

PMID- 27873795
TI  - Chemical Sensors Based on Cyclodextrin Derivatives.
AB  - This review focuses on chemical sensors based on cyclodextrin (CD) derivatives.
      This has been a field of classical interest, and is now of current interest for
      numerous scientists. First, typical chemical sensors using chromophore appended
      CDs are mentioned. Various "turn-off" and "turn-on" fluorescent chemical sensors,
      in which fluorescence intensity was decreased or increased by complexation with
      guest molecules, respectively, were synthesized. Dye modified CDs and photoactive
      metal ion-ligand complex appended CDs, metallocyclodextrins, were also applied
      for chemical sensors. Furthermore, recent novel approaches to chemical sensing
      systems using supramolecular structures such as CD dimers, trimers and
      cooperative binding systems of CDs with the other macrocycle [2]rotaxane and
      supramolecular polymers consisting of CD units are mentioned. New chemical
      sensors using hybrids of CDs with p-conjugated polymers, peptides, DNA,
      nanocarbons and nanoparticles are also described in this review.

PMID- 27873796
TI  - Mapping Regional Distribution of a Single Tree Species: Whitebark Pine in the
      Greater Yellowstone Ecosystem.
AB  - Moderate resolution satellite imagery traditionally has been thought to be
      inadequate for mapping vegetation at the species level. This has made
      comprehensive mapping of regional distributions of sensitive species, such as
      whitebark pine, either impractical or extremely time consuming. We sought to
      determine whether using a combination of moderate resolution satellite imagery
      (Landsat Enhanced Thematic Mapper Plus), extensive stand data collected by land
      management agencies for other purposes, and modern statistical classification
      techniques (boosted classification trees) could result in successful mapping of
      whitebark pine. Overall classification accuracies exceeded 90%, with similar
      individual class accuracies. Accuracies on a localized basis varied based on
      elevation. Accuracies also varied among administrative units, although we were
      not able to determine whether these differences related to inherent spatial
      variations or differences in the quality of available reference data.

PMID- 27873797
TI  - Free Base Porphyrins as Ionophores for Heavy Metal Sensors.
AB  - Two functionalized porphyrins: 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin
      (A) and 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (B) obtained and
      characterized by us were used as ionophores (I) for preparing PVC-based membrane
      sensors selective to Ag+, Pb2+ and Cu2+. The membranes were prepared using three
      different plasticizers: (bis(2-ethylhexyl)sebacate (DOS), dioctylphtalate (DOP),
      o-nitrophenyl octyl ether (NPOE) and potassium tetrakis(4-chlorophenyl)borate
      (KTClPB) as additive. The functional parameters (linear concentration range,
      slope and selectivity) of the sensors with membrane composition:
      (I:PVC:KTClPB:Plasticizer) in different ratios were investigated. The best
      results were obtained for the membranes in the ratio I:PVC:KTClPB:Plasticizer
      10:165:5:330. The influence of pH on the sensors response was studied. The
      sensors were used for a period of four months and their utility has been tested
      on synthetic and real samples.

PMID- 27873798
TI  - Wireless and Powerless Sensing Node System Developed for Monitoring Motors.
AB  - Reliability and maintainability of tooling systems can be improved through
      condition monitoring of motors. However, it is difficult to deploy sensor nodes
      due to the harsh environment of industrial plants. Sensor cables are easily
      damaged, which renders the monitoring system deployed to assure the machine's
      reliability itself unreliable. A wireless and powerless sensing node integrated
      with a MEMS (Micro Electro-Mechanical System) sensor, a signal processor, a
      communication module, and a self-powered generator was developed in this study
      for implementation of an easily mounted network sensor for monitoring motors. A
      specially designed communication module transmits a sequence of electromagnetic
      (EM) pulses in response to the sensor signals. The EM pulses can penetrate
      through the machine's metal case and delivers signals from the sensor inside the
      motor to the external data acquisition center. By using induction power, which is
      generated by the motor's shaft rotation, the sensor node is self-sustaining;
      therefore, no power line is required. A monitoring system, equipped with novel
      sensing nodes, was constructed to test its performance. The test results
      illustrate that, the novel sensing node developed in this study can effectively
      enhance the reliability of the motor monitoring system and it is expected to be a
      valuable technology, which will be available to the plant for implementation in a
      reliable motor management program.

PMID- 27873799
TI  - Detection of Aspens Using High Resolution Aerial Laser Scanning Data and Digital
      Aerial Images.
AB  - The aim was to use high resolution Aerial Laser Scanning (ALS) data and aerial
      images to detect European aspen (Populus tremula L.) from among other deciduous
      trees. The field data consisted of 14 sample plots of 30 m * 30 m size located in
      the Koli National Park in the North Karelia, Eastern Finland. A Canopy Height
      Model (CHM) was interpolated from the ALS data with a pulse density of 3.86/m2,
      low-pass filtered using Height-Based Filtering (HBF) and binarized to create the
      mask needed to separate the ground pixels from the canopy pixels within
      individual areas. Watershed segmentation was applied to the low-pass filtered CHM
      in order to create preliminary canopy segments, from which the non-canopy
      elements were extracted to obtain the final canopy segmentation, i.e. the ground
      mask was analysed against the canopy mask. A manual classification of aerial
      images was employed to separate the canopy segments of deciduous trees from those
      of coniferous trees. Finally, linear discriminant analysis was applied to the
      correctly classified canopy segments of deciduous trees to classify them into
      segments belonging to aspen and those belonging to other deciduous trees. The
      independent variables used in the classification were obtained from the first
      pulse ALS point data. The accuracy of discrimination between aspen and other
      deciduous trees was 78.6%. The independent variables in the classification
      function were the proportion of vegetation hits, the standard deviation of in
      pulse heights, accumulated intensity at the 90th percentile and the proportion of
      laser points reflected at the 60th height percentile. The accuracy of
      classification corresponded to the validation results of earlier ALS-based
      studies on the classification of individual deciduous trees to tree species.

PMID- 27873800
TI  - Surface Temperature Mapping of the University of Northern Iowa Campus Using High
      Resolution Thermal Infrared Aerial Imageries.
AB  - The goal of this project was to map the surface temperature of the University of
      Northern Iowa campus using high-resolution thermal infrared aerial imageries. A
      thermal camera with a spectral bandwidth of 3.0-5.0 MUm was flown at the average
      altitude of 600 m, achieving ground resolution of 29 cm. Ground control data was
      used to construct the pixelto-temperature conversion model, which was later used
      to produce temperature maps of the entire campus and also for validation of the
      model. The temperature map then was used to assess the building rooftop
      conditions and steam line faults in the study area. Assessment of the temperature
      map revealed a number of building structures that may be subject to insulation
      improvement due to their high surface temperatures leaks. Several hot spots were
      also identified on the campus for steam pipelines faults. High-resolution thermal
      infrared imagery proved highly effective tool for precise heat anomaly detection
      on the campus, and it can be used by university facility services for effective
      future maintenance of buildings and grounds.

PMID- 27873801
TI  - Empirical Evidence for Impacts of Internal Migration on Vegetation Dynamics in
      China from 1982 to 2000.
AB  - Migration is one of the major socio-economic characteristics of China since the
      country adopted the policy of economic reform in late 1970s. Many studies have
      been dedicated to understand why and how people move, and the consequences of
      their welfare. The purpose of this study is to investigate the environmental
      impacts of the large scale movement of population in China. We analyzed the trend
      in the Normalized Difference Vegetation Index (NDVI) from the Advanced Very High
      Resolution Radiometer (AVHRR) along with China migration data from the 1 percent
      national survey during 1982-1987, the 4th national census during 1985-1990 and
      the 5th national census during1995~2000. We found that the internal migration in
      China has a statistically significant negative impact on vegetation growth at the
      provincial scale from 1982 to 2000 even though the overall vegetation abundance
      increased in China. The impact from migration (R2=0.47, P=0.0001) on vegetation
      dynamics is the second strongest as among the factors considered, including
      changes in annual mean air temperature (R2=0.50, P=0.0001) and annual total
      precipitation (R2=0.30, P=0.0049) and gross domestic production (R2= 0.25,
      P=0.0102). The negative statistical relationship between the rate of increase in
      total migration and the change in vegetation abundance is stronger (R2=0.56,
      P=0.0000) after controlling for the effects of changes in temperature and
      precipitation. In-migration dominates the impacts of migration on vegetation
      dynamics. Therefore, it is important for policy makers in China to take the
      impacts of migration on vegetation growth into account while making policies
      aiming at sustainable humanenvironment relations.

PMID- 27873802
TI  - A Polypyrrole-based Strain Sensor Dedicated to Measure Bladder Volume in Patients
      with Urinary Dysfunction.
AB  - This paper describes a new technique to measure urine volume in patients with
      urinary bladder dysfunction. Polypyrrole - an electronically conducting polymer -
      is chemically deposited on a highly elastic fabric. This fabric, when placed
      around a phantom bladder, produced a reproducible change in electrical resistance
      on stretching. The resistance response to stretching is linear in 20%-40% strain
      variation. This change in resistance is influenced by chemical fabrication
      conditions. We also demonstrate the dynamic mechanical testing of the patterned
      polypyrrole on fabric in order to show the feasibility of passive interrogation
      of the strain sensor for biomedical sensing applications.

PMID- 27873803
TI  - Electrocatalytic Detection of Amitrole on the Multi-Walled Carbon Nanotube - Iron
      (II) tetra-aminophthalocyanine Platform.
AB  - It is shown that iron(II) tetra-aminophthalocyanine complex electropolymerized
      onto a multi-walled carbon nanotube-modified basal plane pyrolytic graphite
      electrode greatly enhanced the electrocatalytic detetion of amitrole (a toxic
      herbicide), resulting in a very low detection limit (0.5 nM) and excellent
      sensitivity of 8.80+/-0.44 MUA/nM, compared to any known work reported so far.
      The electrocatalytic detection of amitrole at this electrode occurred at less
      positive potential (~0.3 V vs Ag|ACl) and also revealed a typical coupled
      chemical reaction. The mechanism for this response is proposed. The electrode
      gave satisfactory selectivity to amitrole in the presence of other potential
      interfering pesticides in aqueous solutions.

PMID- 27873804
TI  - The Statistical Meaning of Kurtosis and Its New Application to Identification of
      Persons Based on Seismic Signals.
AB  - This paper presents a new algorithm making use of kurtosis, which is a
      statistical parameter, to distinguish the seismic signal generated by a person's
      footsteps from other signals. It is adaptive to any environment and needs no
      machine study or training. As persons or other targets moving on the ground
      generate continuous signals in the form of seismic waves, we can separate
      different targets based on the seismic waves they generate. The parameter of
      kurtosis is sensitive to impulsive signals, so it's much more sensitive to the
      signal generated by person footsteps than other signals generated by vehicles,
      winds, noise, etc. The parameter of kurtosis is usually employed in the financial
      analysis, but rarely used in other fields. In this paper, we make use of kurtosis
      to distinguish person from other targets based on its different sensitivity to
      different signals. Simulation and application results show that this algorithm is
      very effective in distinguishing person from other targets.

PMID- 27873805
TI  - The Improved Dual-view Field Goniometer System FIGOS.
AB  - In spectrodirectional Remote Sensing (RS) the Earth's surface reflectance
      characteristics are studied by means of their angular dimensions. Almost all
      natural surfaces exhibit an individual anisotropic reflectance behaviour due to
      the contrast between the optical properties of surface elements and background
      and the geometric surface properties of the observed scene. The underlying
      concept, which describes the reflectance characteristic of a specific surface
      area, is called the bidirectional reflectance distribution function (BRDF). BRDF
      knowledge is essential for both correction of directional effects in RS data and
      quantitative retrieval of surface parameters. Ground-based spectrodirectional
      measurements are usually performed with goniometer systems. An accurate retrieval
      of the bidirectional reflectance factors (BRF) from field goniometer measurements
      requires hyperspectral knowledge of the angular distribution of the reflected and
      the incident radiation. However, prior to the study at hand, no operational
      goniometer system was able to fulfill this requirement. This study presents the
      first dual-view field goniometer system, which is able to simultaneously collect
      both the reflected and the incident radiation at high angular and spectral
      resolution and, thus, providing the necessary spectrodirectional datasets to
      accurately retrieve the surface specific BRF. Furthermore, the angular
      distribution of the incoming diffuse radiation is characterized for various
      atmospheric conditions and the BRF retrieval is performed for an artificial
      target and compared to laboratory spectrodirectional measurement results obtained
      with the same goniometer system. Suggestions for further improving goniometer
      systems are given and the need for intercalibration of various goniometers as
      well as for standardizing spectrodirectional measurements is expressed.

PMID- 27873806
TI  - A Novel Nonenzymatic Hydrogen Peroxide Sensor Based on a Polypyrrole Nanowire
      Copper Nanocomposite Modified Gold Electrode.
AB  - A novel nonenzymatic hydrogen peroxide (H2O2) sensor has been fabricated by
      dispersing copper nanoparticles onto polypyrrole (PPy) nanowires by cyclic
      voltammetry (CV) to form PPy-copper nanocomposites on gold electrodes. Scanning
      electron microscopy (SEM) was used to characterize the morphologies of the PPy
      nanowires and the PPy-copper nanocomposite. The reactivity of the PPy-copper
      nanocomposite towards H2O2 was characterized by cyclic voltammetry and
      chronoamperometry. Effects of applied potential, the concentrations of detection
      solution upon the response currents of the sensor were investigated for an
      optimum analytical performance. It was proved that the PPy-copper nanocomposite
      showed excellent catalytic activity for the reduction of hydrogen peroxide
      (H2O2). The sensor showed a linear response to hydrogen peroxide in the
      concentration range between 7.0*10-6 and 4.3*10-3 mol L-1 with a high
      sensitivity, and a detection limit of 2.3*10-6 mol L-1. Experiment results also
      showed that the sensor had good stability.

PMID- 27873807
TI  - Biotests and Biosensors for Ecotoxicology of Metal Oxide Nanoparticles: A
      Minireview.
AB  - Nanotechnologies have become a significant priority worldwide. Several
      manufactured nanoparticles - particles with one dimension less than 100 nm - are
      increasingly used in consumer products. At nanosize range, the properties of
      materials differ substantially from bulk materials of the same composition,
      mostly due to the increased specific surface area and reactivity, which may lead
      to increased bioavailability and toxicity. Thus, for the assessment of
      sustainability of nanotechnologies, hazards of manufactured nanoparticles have to
      be studied. Despite all the above mentioned, the data on the potential
      environmental effects of nanoparticles are rare. This mini-review is summarizing
      the emerging information on different aspects of ecotoxicological hazard of metal
      oxide nanoparticles, focusing on TiO2, ZnO and CuO. Various biotests that have
      been successfully used for evaluation of ecotoxic properties of pollutants to
      invertebrates, algae and bacteria and now increasingly applied for evaluation of
      hazard of nanoparticles at different levels of the aquatic food-web are
      discussed. Knowing the benefits and potential drawbacks of these systems, a suite
      of tests for evaluation of environmental hazard of nanoparticles is proposed.
      Special attention is paid to the influence of particle solubility and to
      recombinant metal-sensing bacteria as powerful tools for quantification of metal
      bioavailability. Using recombinant metal-specific bacterial biosensors and
      multitrophic ecotoxicity assays in tandem will create new scientific knowledge on
      the respective role of ionic species and of particles in toxicity of metal oxide
      nanoparticles.

PMID- 27873808
TI  - Critical Evaluation of Acetylcholine Determination in Rat Brain Microdialysates
      using Ion-Pair Liquid Chromatography with Amperometric Detection.
AB  - Liquid chromatography with amperometric detection remains the most widely used
      method for acetylcholine quantification in microdialysis samples. Separation of
      acetylcholine from choline and other matrix components on a microbore
      chromatographic column (1 mm internal diameter), conversion of acetylcholine in
      an immobilized enzyme reactor and detection of the produced hydrogen peroxide on
      a horseradish peroxidase redox polymer coated glassy carbon electrode, achieves
      sufficient sensitivity for acetylcholine quantification in rat brain
      microdialysates. However, a thourough validation within the concentration range
      required for this application has not been carried out before. Furthermore, a
      rapid degradation of the chromatographic columns and enzyme systems have been
      reported. In the present study an ion-pair liquid chromatography assay with
      amperometric detection was validated and its long-term stability evaluated.
      Working at pH 6.5 dramatically increased chromatographic stability without a loss
      in sensitivity compared to higher pH values. The lower limit of quantification of
      the method was 0.3 nM. At this concentration the repeatability was 15.7%, the
      inter-day precision 8.7% and the accuracy 103.6%. The chromatographic column was
      stable over 4 months, the immobilized enzyme reactor up to 2-3 months and the
      enzyme coating of the amperometric detector up to 1-2 months. The concentration
      of acetylcholine in 30 MUl microdialysates obtained under basal conditions from
      the hippocampus of freely moving rats was 0.40 +/- 0.12 nM (mean +/- SD, n = 30).
      The present method is therefore suitable for acetylcholine determination in rat
      brain microdialysates.

PMID- 27873809
TI  - Surface Energy Balance Based Evapotranspiration Mapping in the Texas High Plains.
AB  - Agriculture on the Texas High Plains (THP) uses approximately 89% of groundwater
      withdrawals from the Ogallala Aquifer. Consequently, groundwater levels are
      declining faster than the recharge rate. Therefore, efficient agricultural water
      use is essential for economic viability and sustainability of the THP. Accurate
      regional evapotranspiration (ET) maps would provide valuable information on
      actual crop water use. In this study, METRIC (Mapping Evapotranspiration at High
      Resolution using Internalized Calibration), a remote sensing based ET algorithm,
      was evaluated for mapping ET in the THP. Two Landsat 5 Thematic Mapper images
      acquired on 27 June (DOY 178) and 29 July (DOY 210) 2005 were used for this
      purpose. The performance of the ET model was evaluated by comparing the predicted
      daily ET with values derived from soil moisture budget at four commercial
      agricultural fields. Daily ET estimates resulted with a prediction error of
      12.7+/-8.1% (mean bias error +/- root mean square error) on DOY 178 and -4.7+/
      9.4% on DOY 210 when compared with ET derived from measured soil moisture through
      the soil water balance. These results are good considering the prevailing
      advective conditions in the THP. METRIC have the potential to be used for mapping
      regional ET in the THP region. However, more evaluation is needed under different
      agroclimatological conditions.

PMID- 27873811
TI  - Diagnosis of Intoxication by the Organophosphate VX: Comparison Between an
      Electrochemical Sensor and Ellman's Photometric Method.
AB  - An electrochemical sensor is introduced as a tool applicable for diagnosis of
      intoxication by cholinesterase inhibitors caused by the well-known nerve agent
      VX. The traditional Ellman method was chosen for comparison with the sensor's
      analytical parameters. Both methods are based on estimation of blood
      cholinesterase inhibition as a marker of intoxication. While Ellman's method
      provided a limit of detection of 5.2'10-7 M for blood containing VX, the
      electrochemical sensor was able to detect 4.0'10-7 M. Good correlation between
      both methods was observed (R = 0.92). The electrochemical sensor could be
      considered a convenient tool for a fast yet accurate method, easily available for
      field as well as laboratory use. Time and cost savings are key features of the
      sensor-based assay.

PMID- 27873812
TI  - Retrieval Algorithms for Road Surface Modelling Using Laser-Based Mobile Mapping.
AB  - Automated processing of the data provided by a laser-based mobile mapping system
      will be a necessity due to the huge amount of data produced. In the future,
      vehiclebased laser scanning, here called mobile mapping, should see considerable
      use for road environment modelling. Since the geometry of the scanning and point
      density is different from airborne laser scanning, new algorithms are needed for
      information extraction. In this paper, we propose automatic methods for
      classifying the road marking and kerbstone points and modelling the road surface
      as a triangulated irregular network. On the basis of experimental tests, the mean
      classification accuracies obtained using automatic method for lines, zebra
      crossings and kerbstones were 80.6%, 92.3% and 79.7%, respectively.

PMID- 27873810
TI  - Mesoporous Silicate Materials in Sensing.
AB  - Mesoporous silicas, especially those exhibiting ordered pore systems and uniform
      pore diameters, have shown great potential for sensing applications in recent
      years. Morphological control grants them versatility in the method of deployment
      whether as bulk powders, monoliths, thin films, or embedded in coatings. High
      surface areas and pore sizes greater than 2 nm make them effective as adsorbent
      coatings for humidity sensors. The pore networks also provide the potential for
      immobilization of enzymes within the materials. Functionalization of materials by
      silane grafting or through cocondensation of silicate precursors can be used to
      provide mesoporous materials with a variety of fluorescent probes as well as
      surface properties that aid in selective detection of specific analytes. This
      review will illustrate how mesoporous silicas have been applied to sensing
      changes in relative humidity, changes in pH, metal cations, toxic industrial
      compounds, volatile organic compounds, small molecules and ions, nitroenergetic
      compounds, and biologically relevant molecules.

PMID- 27873814
TI  - Deriving Vegetation Dynamics of Natural Terrestrial Ecosystems from MODIS
      NDVI/EVI Data over Turkey.
AB  - The 16-day composite MODIS vegetation indices (VIs) at 500-m resolution for the
      period between 2000 to 2007 were seasonally averaged on the basis of the
      estimated distribution of 16 potential natural terrestrial ecosystems (NTEs)
      across Turkey. Graphical and statistical analyses of the time-series VIs for the
      NTEs spatially disaggregated in terms of biogeoclimate zones and land cover types
      included descriptive statistics, correlations, discrete Fourier transform (DFT),
      time-series decomposition, and simple linear regression (SLR) models. Our spatio
      temporal analyses revealed that both MODIS VIs, on average, depicted similar
      seasonal variations for the NTEs, with the NDVI values having higher mean and SD
      values. The seasonal VIs were most correlated in decreasing order for:
      barren/sparsely vegetated land > grassland > shrubland/woodland > forest;
      (sub)nival > warm temperate > alpine > cool temperate > boreal = Mediterranean;
      and summer > spring > autumn > winter. Most pronounced differences between the
      MODIS VI responses over Turkey occurred in boreal and Mediterranean climate zones
      and forests, and in winter (the senescence phase of the growing season). Our
      results showed the potential of the time-series MODIS VI datasets in the
      estimation and monitoring of seasonal and interannual ecosystem dynamics over
      Turkey that needs to be further improved and refined through systematic and
      extensive field measurements and validations across various biomes.

PMID- 27873813
TI  - Sodium Gill Potential as a Tool to Monitor Valve Closure Behavior in Freshwater
      Clam Corbicula fluminea in Response to Copper.
AB  - Valve closure behavior in freshwater clam Corbicula fluminea is a biologically
      sensitive endpoint. The purpose of this paper was to derive an
      electrophysiological response model of C. fluminea to assess copper (Cu)-sodium
      (Na) interactions in gill membrane, whereby valve closure behavior and Cu
      toxicity could be monitored. The proposed model was based on the integration of
      Cu bioavailability, Na and Cu internalizations, and electrochemically-based gill
      potentials. Based on Na active transport under non-equilibrium conditions,
      predicted gill potential of -8.2 mV agreed reasonably well with published the
      measured transepithelial potential of -7 mV in C. fluminea. Our proposed
      framework captured the general features observed in model applications including:
      (i) 50% inhibitory Cu2+ activities for Na membrane potential (ENa) and uptake
      rate (JNa) were estimated to be 0.072 and 0.043 mM, respectively, with a
      stoichiometry of 3Cu2+: 1ENa and 1JNa; (ii) the external Cu2+-dependent internal
      Na concentration could be parsimoniously estimated, and (iii) the site-specific
      clam gill potentials could be monitored. Here we provided a new approach to
      monitor waterborne metal toxicity to reduce the nationwide economic losses due to
      bans on harvesting of contaminated clam and the potential risks to the health of
      clams.

PMID- 27873815
TI  - Amperometric Biosensors for Real Time Assays of Organophosphates.
AB  - An amperometric biosensor based on acetylcholinesterase (AChE) immobilized in
      gelatin was used to develop an assay for the organophosphate paraoxon. The more
      traditional manner employing preincubation was used for comparison between
      measurement procedures, although the aim of the study was to examine the
      performance of the biosensor for real time monitoring of organophosphates. The
      biosensor was immersed in a reaction chamber and paraoxon was injected inside. We
      were able to detect 200 pg of paraoxon within one minute or 2.5 ppb when the
      biosensor was preincubed in the sample solution for 15 minutes. The practical
      impact and expectations are discussed.

PMID- 27873816
TI  - Extended Calix[4]arene-Based Receptors for Molecular Recognition and Sensing.
AB  - Recent advances in the area of recognition and sensing have shown that artificial
      receptors derived from extended calix[4]arenes bearing multiple pi-conjugated
      fluorophoric or chromophoric systems have found useful to enhance binding
      affinity, selectivity and sensitivity for recognition and sensing of a targeted
      ion or molecule. A comprehensive review of various pi-conjugation-extended
      calyx[4]arene-based receptors with the highlight on the design and binding
      characterization for recognition and sensing is presented.

PMID- 27873817
TI  - Monolithic Active Pixel Sensors (MAPS) in a Quadruple Well Technology for Nearly
      100% Fill Factor and Full CMOS Pixels.
AB  - In this paper we present a novel, quadruple well process developed in a modern
      0.18 mm CMOS technology called INMAPS. On top of the standard process, we have
      added a deep P implant that can be used to form a deep P-well and provide
      screening of N-wells from the P-doped epitaxial layer. This prevents the
      collection of radiation-induced charge by unrelated N-wells, typically ones where
      PMOS transistors are integrated. The design of a sensor specifically tailored to
      a particle physics experiment is presented, where each 50 mm pixel has over 150
      PMOS and NMOS transistors. The sensor has been fabricated in the INMAPS process
      and first experimental evidence of the effectiveness of this process on charge
      collection is presented, showing a significant improvement in efficiency.

PMID- 27873818
TI  - Neuromorphic VLSI Models of Selective Attention: From Single Chip Vision Sensors
      to Multi-chip Systems.
AB  - Biological organisms perform complex selective attention operations continuously
      and effortlessly. These operations allow them to quickly determine the motor
      actions to take in response to combinations of external stimuli and internal
      states, and to pay attention to subsets of sensory inputs suppressing non salient
      ones. Selective attention strategies are extremely effective in both natural and
      artificial systems which have to cope with large amounts of input data and have
      limited computational resources. One of the main computational primitives used to
      perform these selection operations is the Winner-Take-All (WTA) network. These
      types of networks are formed by arrays of coupled computational nodes that
      selectively amplify the strongest input signals, and suppress the weaker ones.
      Neuromorphic circuits are an optimal medium for constructing WTA networks and for
      implementing efficient hardware models of selective attention systems. In this
      paper we present an overview of selective attention systems based on neuromorphic
      WTA circuits ranging from single-chip vision sensors for selecting and tracking
      the position of salient features, to multi-chip systems implement saliency-map
      based models of selective attention.

PMID- 27873819
TI  - Verifying Pressure of Water on Dams, a Case Study.
AB  - Sensing and monitoring deformation pattern of dams is often one of the most
      effective ways to understand their safety status. The main objective of the
      present study is to find the extent to which rising reservoir level affects the
      mechanism of deformation of the Yamula dam under certain changes in the reservoir
      level conditions during the first filling period. A new dynamic deformation
      analysis technique was developed to analyze four geodetic monitoring records
      consisting of vertical and horizontal displacements of nine object points
      established on the dam and six reference points surrounding it, to see whether
      the rising reservoir level is responsible for the vertical and horizontal
      deformations during the first filling period. The largest displacements were
      determined in the middle points of the dam construction. There is an apparent
      linear relationship between the dam subsidence and the reservoir level. The
      dynamic deformation model was developed to model this situation. The model infers
      a causative relationship between the reservoir level and the dam deformations.
      The analysis of the results determines the degree of the correlation between the
      change in the reservoir level and the observed structural deformation of the dam.

PMID- 27873820
TI  - Drift and Hysteresis Characteristics of Drug Sensors Based on Ruthenium Dioxide
      Membrane.
AB  - The drug sensing properties of procaine and berberine drug sensors based on
      ruthenium dioxide thin film were investigated. Ruthenium dioxide (RuO2) membrane
      prepared using a sputtering method was used as substrates for the drug sensors.
      The procaine and berberine drug sensors were prepared using a drug-sensitive
      membrane that measured the procaine and berberine concentration in a linear range
      from 1*10-2 M to 1*10-6 M and from 1*10-2 M to 1*10-7 M, respectively. The drift
      rates and hyteresis widths of these ruthenium dioxide based drug sensors were
      also investigated.

PMID- 27873821
TI  - Long-term Satellite NDVI Data Sets: Evaluating Their Ability to Detect Ecosystem
      Functional Changes in South America.
AB  - In the last decades, South American ecosystems underwent important functional
      modifications due to climate alterations and direct human intervention on land
      use and land cover. Among remotely sensed data sets, NOAA-AVHRR "Normalized
      Difference Vegetation Index" (NDVI) represents one of the most powerful tools to
      evaluate these changes thanks to their extended temporal coverage. In this paper
      we explored the possibilities and limitations of three commonly used NOAA-AVHRR
      NDVI series (PAL, GIMMS and FASIR) to detect ecosystem functional changes in the
      South American continent. We performed pixel-based linear regressions for four
      NDVI variables (average annual, maximum annual, minimum annual and intra-annual
      coefficient of variation) for the 1982-1999 period and (1) analyzed the
      convergences and divergences of significant multi-annual trends identified across
      all series, (2) explored the degree of aggregation of the trends using the O-ring
      statistic, and (3) evaluated observed trends using independent information on
      ecosystem functional changes in five focal regions. Several differences arose in
      terms of the patterns of change (the sign, localization and total number of
      pixels with changes). FASIR presented the highest proportion of changing pixels
      (32.7%) and GIMMS the lowest (16.2%). PAL and FASIR data sets showed the highest
      agreement, with a convergence of detected trends on 71.2% of the pixels. Even
      though positive and negative changes showed substantial spatial aggregation,
      important differences in the scale of aggregation emerged among the series, with
      GIMMS showing the smaller scale (<=11 pixels). The independent evaluations
      suggest higher accuracy in the detection of ecosystem changes among PAL and FASIR
      series than with GIMMS, as they detected trends that match expected shifts. In
      fact, this last series eliminated most of the long term patterns over the
      continent. For example, in the "Eastern Paraguay" and "Uruguay River margins"
      focal regions, the extensive changes due to land use and land cover change
      expansion were detected by PAL and FASIR, but completely ignored by GIMMS.
      Although the technical explanation of the differences remains unclear and needs
      further exploration, we found that the evaluation of this type of remote sensing
      tools should not only be focused at the level of assumptions (i.e. physical or
      mathematical aspects of image processing), but also at the level of results (i.e.
      contrasting observed patterns with independent proofs of change). We finally
      present the online collaborative initiative "Land ecosystem change utility for
      South America", which facilitates this type of evaluations and helps to identify
      the most important functional changes of the continent.

PMID- 27873822
TI  - Atmospheric Effects on InSAR Measurements and Their Mitigation.
AB  - Interferometric Synthetic Aperture Radar (InSAR) is a powerful technology for
      observing the Earth surface, especially for mapping the Earth's topography and
      deformations. InSAR measurements are however often significantly affected by the
      atmosphere as the radar signals propagate through the atmosphere whose state
      varies both in space and in time. Great efforts have been made in recent years to
      better understand the properties of the atmospheric effects and to develop
      methods for mitigating the effects. This paper provides a systematic review of
      the work carried out in this area. The basic principles of atmospheric effects on
      repeat-pass InSAR are first introduced. The studies on the properties of the
      atmospheric effects, including the magnitudes of the effects determined in the
      various parts of the world, the spectra of the atmospheric effects, the isotropic
      properties and the statistical distributions of the effects, are then discussed.
      The various methods developed for mitigating the atmospheric effects are then
      reviewed, including the methods that are based on PSInSAR processing, the methods
      that are based on interferogram modeling, and those that are based on external
      data such as GPS observations, ground meteorological data, and satellite data
      including those from the MODIS and MERIS. Two examples that use MODIS and MERIS
      data respectively to calibrate atmospheric effects on InSAR are also given.

PMID- 27873823
TI  - Analyzing Land Use Changes in the Metropolitan Jilin City of Northeastern China
      Using Remote Sensing and GIS.
AB  - Remote sensing and GIS have been widely employed to study temporal and spatial
      urban land use changes in southern and southeastern China. However, few studies
      have been conducted in northeastern regions. This study analyzed land use change
      and spatial patterns of urban expansion in the metropolitan area of Jilin City,
      located on the extension of Changbai Mountain, based on aerial photos from 1989
      and 2005 Spot images. The results indicated that urban land and transportation
      land increased dramatically (by 94.04% and 211.20%, respectively); isolated
      industrial and mining land decreased moderately (by 29.54%); rural residential
      land increased moderately (by 26.48%); dry land and paddy fields increased
      slightly (by 15.68% and 11.78%, respectively); forest and orchards decreased
      slightly (by 5.27% and 4.61%, respectively); grasslands and unused land decreased
      dramatically (by 99.12% and 86.04%, respectively). Sloped dry land (more than 4
      degrees) was mainly distributed on the land below 10 degrees with an east,
      southeastern and south sunny direction aspect, and most sloped dry land
      transformed to forest was located on an east aspect lower than 12 degrees, while
      forest changed to dry land were mainly distributed on east and south aspects
      lower than 10 degrees. A spatial dependency analysis of land use change showed
      that the increased urban land was a logarithmic function of distance to the
      Songhua River. This study also provided some data with spatial details about the
      uneven land development in the upstream areas of Songhua River basin.

PMID- 27873825
TI  - Impact of Soil Moisture Dynamics on ASAR sigmao Signatures and Its Spatial
      Variability Observed over the Tibetan Plateau.
AB  - This paper reports on the analysis of a 2.5 year-long time series of ASAR wide
      swath mode (WSM) observations for characterizing the soil moisture dynamics. The
      employed ASAR WSM data set consists of 152 VV-polarized scenes acquired in the
      period between April 2005 and September 2007 over the Naqu river basin located on
      the Tibetan Plateau. For four different spatial domains, with areas of 30x30 km2,
      5x5 km2 and (two domains of) 1x1 km2, the mean backscatter (sigmao) and the
      standard deviation (stdev) have been computed for each ASAR acquisition.
      Comparison of the mean sigmao values with the stdev values results in a specific
      triangular distribution of data points for all spatial domains. Analysis of the
      mean sigmao and stdev with respect to in-situ soil moisture measurements
      demonstrates that this triangular shaped distribution can be explained by soil
      moisture dynamics during monsoon and winter periods. This shows that the
      relationship between the spatial mean soil moisture and variability is not
      uniquely defined and may change throughout seasons. Downscaling of coarse
      resolution soil moisture products should, therefore, be ideally based on
      additional near real time data sources. In this context, the presented results
      could form a basis for the development of SAR-based soil moisture downscaling
      methodologies.

PMID- 27873824
TI  - Mid-Infrared Tunable Resonant Cavity Enhanced Detectors.
AB  - Mid-infrared detectors that are sensitive only in a tunable narrow spectral band
      are presented. They are based on the Resonant Cavity Enhanced Detector (RCED)
      principle and employing a thin active region using IV-VI narrow gap semiconductor
      layers. A Fabry-Perot cavity is formed by two mirrors. The active layer is grown
      onto one mirror, while the second mirror can be displaced. This changes the
      cavity length thus shifting the resonances where the detector is sensitive. Using
      electrostatically actuated MEMS micromirrors, a very compact tunable detector
      system has been fabricated. Mirror movements of more than 3 MUm at 30V are
      obtained. With these mirrors, detectors with a wavelength tuning range of about
      0.7 MUm have been realized. Single detectors can be used in mid-infrared micro
      spectrometers, while a detector arrangement in an array makes it possible to
      realize Adaptive Focal Plane Arrays (AFPA).

PMID- 27873826
TI  - An Amperometric Biosensor for Uric Acid Determination Prepared From Uricase
      Immobilized in Polyaniline-Polypyrrole Film.
AB  - A new amperometric uric acid biosensor was developed by immobilizing uricase by a
      glutaraldehyde crosslinking procedure on polyaniline-polypyrrole (pani-ppy)
      composite film on the surface of a platinum electrode. Determination of uric acid
      was performed by the oxidation of enzymatically generated H2O2 at 0.4 V vs.
      Ag/AgCl. The linear working range of the biosensor was 2.5*10-6 - 8.5*10-5 M and
      the response time was about 70 s. The effects of pH, temperature were
      investigated and optimum parameters were found to be 9.0, 55 oC, respectively.
      The stability and reproducibility of the enzyme electrode have been also studied.

PMID- 27873827
TI  - Integrated Design and Implementation of Embedded Control Systems with Scilab.
AB  - Embedded systems are playing an increasingly important role in control
      engineering. Despite their popularity, embedded systems are generally subject to
      resource constraints and it is therefore difficult to build complex control
      systems on embedded platforms. Traditionally, the design and implementation of
      control systems are often separated, which causes the development of embedded
      control systems to be highly timeconsuming and costly. To address these problems,
      this paper presents a low-cost, reusable, reconfigurable platform that enables
      integrated design and implementation of embedded control systems. To minimize the
      cost, free and open source software packages such as Linux and Scilab are used.
      Scilab is ported to the embedded ARM-Linux system. The drivers for interfacing
      Scilab with several communication protocols including serial, Ethernet, and
      Modbus are developed. Experiments are conducted to test the developed embedded
      platform. The use of Scilab enables implementation of complex control algorithms
      on embedded platforms. With the developed platform, it is possible to perform all
      phases of the development cycle of embedded control systems in a unified
      environment, thus facilitating the reduction of development time and cost.

PMID- 27873828
TI  - A Role for Adenosine A1 Receptors in GABA and NMDA-Receptor Mediated Modulation
      of Dopamine Release: Studies Using Fast Cyclic Voltammetry.
AB  - In the striatum many neurotransmitters including GABA, glutamate, acetylcholine,
      dopamine, nitric oxide and adenosine interact to regulate synaptic transmission.
      Dopamine release in the striatum is regulated by a number of pre- and
      postsynaptic receptors including adenosine. We have recently shown using isolated
      rat striatal slices, and the technique of fast cyclic voltammetry, that adenosine
      A1 receptor-mediated inhibition of dopamine release is modulated by dopamine D1
      receptors. In the present study we have investigated the influence of NMDA and
      GABA receptor activation on the modulation of electrically stimulated dopamine
      release by adenosine. Application of the adenosine A1 receptor agonist, N6
      cyclopentyladenosine (CPA), concentration-dependently inhibited dopamine release
      to a maxiumum of 50%. Perfusion of the glutamate receptor agonist, NMDA, in low
      magnesium, caused a rapid and concentration-dependent inhibition of dopamine
      release. Prior perfusion with the adenosine A1 receptor antagonist, DPCPX,
      significantly reduced the effect of 5 mM and 10 mM NMDA on dopamine release. The
      GABAA receptor agonist, isoguvacine, had a significant concentration-dependent
      inhibitory effect on dopamine release which was reversed by prior application of
      the GABAA receptor antagonist, picrotoxin, but not DPCPX. Finally inhibition of
      dopamine release by CPA (1mM) was significantly enhanced by prior perfusion with
      picrotoxin. These data demonstrate an important role for GABA, NMDA and adenosine
      in the modulation of dopamine release.

PMID- 27873830
TI  - The Graphical Cadastre Problem in Turkey: The Case of Trabzon Province.
AB  - Cadastral projects in Turkey have been accelerated in recent years by the
      involvement of the private sector. These projects aim at completing the country's
      cadastre, along with producing bases in standards that could be a foundation for
      Land Registry and Cadastre Information System (LRCIS). It is possible to produce
      cadastral data with today's technological means. In this context, three
      dimensional cadastre data can be properly produced, especially in digital
      cadastre projects with the required point accuracy. Nevertheless this is not
      enough for LRCIS. The cadastre bases that have been produced so far by different
      methods with different scales and bases, with or without coordinates, should also
      be converted into digital form based on National Basic GPS Network of Turkey
      (NBGN) in required point-location accuracy. As the result of evaluation of
      graphical cadastre bases produced without coordinates, actual land measurements,
      and information obtained from sheets and field book data together, it was found
      out that there are significant base problems in the graphical maps. These bases,
      comprising 20% of Turkey's cadastre constitutes the most important bottleneck of
      completing the country's cadastre. In the scope of this paper, the possibilities
      of converting the field book measurement values of graphic cadastre bases into
      digital forms in national coordinate system by comparing them with actual land
      measurements are investigated, along with Turkey's Cadastre and its problems.

PMID- 27873831
TI  - Quantitative Hyperspectral Reflectance Imaging.
AB  - Hyperspectral imaging is a non-destructive optical analysis technique that can
      for instance be used to obtain information from cultural heritage objects
      unavailable with conventional colour or multi-spectral photography. This
      technique can be used to distinguish and recognize materials, to enhance the
      visibility of faint or obscured features, to detect signs of degradation and
      study the effect of environmental conditions on the object. We describe the basic
      concept, working principles, construction and performance of a laboratory
      instrument specifically developed for the analysis of historical documents. The
      instrument measures calibrated spectral reflectance images at 70 wavelengths
      ranging from 365 to 1100 nm (near-ultraviolet, visible and near-infrared). By
      using a wavelength tunable narrow-bandwidth light-source, the light energy used
      to illuminate the measured object is minimal, so that any light-induced
      degradation can be excluded. Basic analysis of the hyperspectral data includes a
      qualitative comparison of the spectral images and the extraction of quantitative
      data such as mean spectral reflectance curves and statistical information from
      user-defined regions-of-interest. More sophisticated mathematical feature
      extraction and classification techniques can be used to map areas on the
      document, where different types of ink had been applied or where one ink shows
      various degrees of degradation. The developed quantitative hyperspectral imager
      is currently in use by the Nationaal Archief (National Archives of The
      Netherlands) to study degradation effects of artificial samples and original
      documents, exposed in their permanent exhibition area or stored in their deposit
      rooms.

PMID- 27873829
TI  - Over-the-Counter Biosensors: Past, Present, and Future.
AB  - The demand for specific, low cost, rapid, sensitive and easy detection of
      biomolecules is huge. A well-known example is the glucose meters used by
      diabetics to monitor their blood glucose levels. Nowadays, a vast majority of the
      glucose meters are based on electrochemical biosensor technology. The inherent
      small size and simple construction of the electrochemical transducer and
      instrument are ideally suited for pointof-care biosensing. Besides glucose, a
      wide variety of electrochemical biosensors have been developed for the
      measurements of some other key metabolites, proteins, and nucleic acids.
      Nevertheless, unlike the glucose meters, limited success has been achieved for
      the commercialization of the protein and nucleic acid biosensors. In this review
      article, key technologies on the electrochemical detection of key metabolites,
      proteins, and DNAs are discussed in detail, with particular emphasis on those
      that are compatible to home-use setting. Moreover, emerging technologies of lab
      on-a-chip microdevices and nanosensors (i.e., silicon and carbon nanotube field
      effect sensors) offer opportunities for the construction of new generation
      biosensors with much better performances. Together with the continuous
      innovations in the basic components of biosensors (i.e., transducers,
      biorecognition molecules, immobilization and signal transduction schemes),
      consumers could soon buy different kinds of biosensing devices in the pharmacy
      stores.

PMID- 27873833
TI  - Immobilization of the Enzyme Glucose Oxidase on Both Bulk and Porous SiO2
      Surfaces.
AB  - Silicon dioxide surfaces, both bulk and porous, were used to anchor the enzyme
      glucose oxidase. The immobilization protocol was optimized and the samples
      characterized using X-ray Photoelectron Spectroscopy, Energy Dispersive X-rays
      coupled to scanning electron microscopy and enzymatic activity measurements. We
      show that a uniform layer was obtained by activating the oxide before
      immobilization. X-ray Photoelectron Spectroscopy measurements carried out on bulk
      oxide showed that the silicon substrate signal was fully screened after the
      enzyme deposition showing the absence of uncovered surface regions. The enzyme
      presence was detected monitoring both the C 1s and N 1s signals. Finally,
      enzymatic activity measurements confirmed that the glucose oxidase activity was
      preserved after immobilization and maintained after three months of shelf life if
      the sample was properly stored. The importance of using porous silicon oxide to
      maximize the surface area was also evidenced.

PMID- 27873832
TI  - Amperometric Sensor for Detection of Chloride Ions.
AB  - Chloride ion sensing is important in many fields such as clinical diagnosis,
      environmental monitoring and industrial applications. We have measured chloride
      ions at a carbon paste electrode (CPE) and at a CPE modified with solid AgNO3, a
      solution of AgNO3 and/or solid silver particles. Detection limits (3 S/N) for
      chloride ions were 100 MUM, 100 MUM and 10 MUM for solid AgNO3, solution of AgNO3
      and/or solid silver particles, respectively. The CPE modified with silver
      particles is the most sensitive to the presence chloride ions. After that we
      approached to the miniaturization of the whole electrochemical instrument.
      Measurements were carried out on miniaturized instrument consisting of a
      potentiostat with dimensions 35 * 166 * 125 mm, screen printed electrodes, a
      peristaltic pump and a PC with control software. Under the most suitable
      experimental conditions (Britton-Robinson buffer, pH 1.8 and working electrode
      potential 550 mV) we estimated the limit of detection (3 S/N) as 500 nM.

PMID- 27873834
TI  - Electrochemical Behaviors of Methylene Blue on DNA Modified Electrode and Its
      Application to the Detection of PCR Product from NOS Sequence.
AB  - An electrochemical DNA biosensor for the detection of NOS gene sequences from
      genetically modified organisms (GMOs) is presented in this paper. Single-stranded
      DNA (ssDNA) was covalently attached through the carboxylate ester formed by the
      3'- hydroxy end of the DNA with the carboxyl of a mercaptoacetic acid self
      assembled monolayer-modified gold electrode using N-hydroxysuccinimide (NHS) and
      N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) as linkers.
      The electrochemical behavior of methylene blue (MB) on the ssDNA and dsDNA
      modified gold electrode were carefully studied. Compared with ssDNA/Au electrode,
      an increase of redox peak current of MB on dsDNA/Au electrode was found, which
      could be further used for monitoring the recognition of DNA hybridization. Based
      on this result, the polymerase chain reaction (PCR) product of the common inserts
      NOS terminator from real GMOs samples was detected successfully.

PMID- 27873835
TI  - An Immunosensing System Using Stilbene Glycoside as a Fluorogenic Substrate for
      an Enzymatic Reaction Model.
AB  - A natural product, stilbene glycoside (2,3,5,4'-tetrahydroxydiphenylethylene-2-O
      glucoside, TBG), has been evaluated for the first time as a potential substrate
      for horseradish peroxidase (HRP)-catalyzed fluorogenic reactions. The properties
      of TBG as a fluorogenic substrate for HRP and its application in a fluorometric
      enzyme-linked immunosensing system were compared with commercially available
      substrates such as p-hydroxyphenylpropionic acid (pHPPA), chavicol and Amplex red
      using Brucella melitensis antibody (BrAb) as a model analyte. The immunosensing
      body based on HRP-BrAb was constructed by dispersing graphite, BrAg and paraffin
      wax at room temperature. In a competitive immunoassay procedure, the BrAb
      competed with HRP-BrAb to react with the immobilized BrAg. In the enzymatic
      reaction, the binding HRP-BrAb on the sensing body surface can catalyze the
      polymerization reaction of TBG by H2O2 forming fluorescent dimers and causing an
      increase in fluorescence intensity. TBG showed comparable ability for HRP
      detection and its enzyme-linked immunosensing reaction system, in a linear
      detection ranging of 3.5'10-8~7.6'10-6g/L and with a detection limit of 1.7'10-9
      g/L. The immobilized biocomposite surface could be regenerated with excellent
      reproducibility (RSD=3.8%) by simply polishing with an alumina paper. The
      proposed immunosensing system has been used to determine the BrAb in rabbit serum
      samples with satisfactory results.

PMID- 27873837
TI  - Value Benefit Analysis Software and Its Application in Bolu-Lake Abant Natural
      Park.
AB  - Value benefit analysis (VBA) is a psychometric instrument for finding the best
      compromise in forestry multiple-use planning, when the multiple objectives cannot
      be expressed in the same physical or monetary unit. It insures a systematic
      assessment of the consequences of proposed alternatives and thoroughly documents
      the decision process. The method leads to a ranking of alternatives based upon
      weighting of the objectives and evaluation of the contribution of each
      alternative to these objectives. The use of the method is illustrated with
      hypothetical data about Bolu-Lake Abant Natural Park (BLANP). In this study, in
      addition, computer software controlling the confidence was created. This software
      puts into practice the method proposed by Churchman and Ackoff, and determines
      the significance of the alternatives quickly and accurately.

PMID- 27873836
TI  - Thermographic Phosphors for High Temperature Measurements: Principles, Current
      State of the Art and Recent Applications.
AB  - This paper reviews the state of phosphor thermometry, focusing on developments in
      the past 15 years. The fundamental principles and theory are presented, and the
      various spectral and temporal modes, including the lifetime decay, rise time and
      intensity ratio, are discussed. The entire phosphor measurement system, including
      relative advantages to conventional methods, choice of phosphors, bonding
      techniques, excitation sources and emission detection, is reviewed. Special
      attention is given to issues that may arise at high temperatures. A number of
      recent developments and applications are surveyed, with examples including:
      measurements in engines, hypersonic wind tunnel experiments, pyrolysis studies
      and droplet/spray/gas temperature determination. They show the technique is
      flexible and successful in measuring temperatures where conventional methods may
      prove to be unsuitable.

PMID- 27873838
TI  - Electrical Characterization of Microelectromechanical Silicon Carbide Resonators.
AB  - This manuscript describes the findings of a study to investigate the performance
      of SiC MEMS resonators with respect to resonant frequency and quality factor
      under a variety of testing conditions, including various ambient pressures, AC
      drive voltages, bias potentials and temperatures. The sample set included both
      single-crystal and polycrystalline 3C-SiC lateral resonators. The experimental
      results show that operation at reduced pressures increases the resonant frequency
      as damping due to the gas-rarefaction effect becomes significant. Both DC bias
      and AC drive voltages result in nonlinearities, but the AC drive voltage is more
      sensitive to noise. The AC voltage has a voltage coefficient of 1~4ppm/V at a DC
      bias of 40V. The coefficient of DC bias is about -11ppm/V to - 21ppm/V for poly
      SiC, which is more than a factor of two better than a similarly designed
      polysilicon resonator (-54 ppm/V). The effective stiffness of the resonator
      decreases (softens) as the bias potential is increased, but increases (hardens)
      as drive voltage increase when scan is from low to high frequency. The resonant
      frequency decreases slightly with increasing temperature, exhibiting a
      temperature coefficient of -22 ppm/oC, between 22oC and 60oC. The thermal
      expansion mismatch between the SiC device and the Si substrate could be a reason
      that thermal coefficient for these SiC resonators is about twofold higher than
      similar polysilicon resonators. However, the Qs appear to exhibit no temperature
      dependence in this range.

PMID- 27873839
TI  - Use of Fe3O4 Nanoparticles for Enhancement of Biosensor Response to the Herbicide
      2,4-Dichlorophenoxyacetic Acid.
AB  - Magnetic nanoparticles of Fe3O4 were synthesized and characterized using
      transmission electron microscopy and X-ray diffraction. The Fe3O4 nanoparticles
      were found to have an average diameter of 5.48 +/-1.37 nm. An electrochemical
      biosensor based on immobilized alkaline phosphatase (ALP) and Fe3O4 nanoparticles
      was studied. The amperometric biosensor was based on the reaction of ALP with the
      substrate ascorbic acid 2-phosphate (AA2P). The incorporation of the Fe3O4
      nanoparticles together with ALP into a sol gel/chitosan biosensor membrane has
      led to the enhancement of the biosensor response, with an improved linear
      response range to the substrate AA2P (5-120 MUM) and increased sensitivity. Using
      the inhibition property of the ALP, the biosensor was applied to the
      determination of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). The use of
      Fe3O4 nanoparticles gives a two-fold improvement in the sensitivity towards 2,4
      D, with a linear response range of 0.5-30 MUgL-1. Exposure of the biosensor to
      other toxicants such as heavy metals demonstrated only slight interference from
      metals such as Hg2+, Cu2+, Ag2+ and Pb2+. The biosensor was shown to be useful
      for the determination of the herbicide 2, 4-D because good recovery of 95-100
      percent was obtained, even though the analysis was performed in water samples
      with a complex matrix. Furthermore, the results from the analysis of 2,4-D in
      water samples using the biosensor correlated well with a HPLC method.

PMID- 27873840
TI  - Electrochemical Preparation of a Molecularly Imprinted Polypyrrole-modified
      Pencil Graphite Electrode for Determination of Ascorbic Acid.
AB  - A molecularly imprinted polymer (MIP) polypyrrole (PPy)-based film was fabricated
      for the determination of ascorbic acid. The film was prepared by incorporation of
      a template molecule (ascorbic acid) during the electropolymerization of pyrrole
      onto a pencil graphite electrode (PGE) in aqueous solution using a cyclic
      voltammetry method. The performance of the imprinted and non-imprinted (NIP)
      films was evaluated by differential pulse voltammetry (DPV). The effect of pH,
      monomer and template concentrations, electropolymerization cycles and
      interferents on the performance of the MIP electrode was investigated and
      optimized. The molecularly imprinted film exhibited a high selectivity and
      sensitivity toward ascorbic acid. The DPV peak current showed a linear dependence
      on the ascorbic acid concentration and a linear calibration curve was obtained in
      the range of 0.25 to 7.0 mM of ascorbic acid with a correlation coefficient of
      0.9946. The detection limit (3sigma) was determined as 7.4x10-5 M (S/N=3). The
      molecularly-imprinted polypyrrole-modified pencil graphite electrode showed a
      stable and reproducible response, without any influence of interferents commonly
      existing in pharmaceutical samples. The proposed method is simple and quick. The
      PPy electrodes have a low response time, good mechanical stability and are
      disposable simple to construct.

PMID- 27873841
TI  - Voltammetric Detection of Urea on an Ag-Modified Zeolite-Expanded Graphite-Epoxy
      Composite Electrode.
AB  - In this paper, a modified expanded graphite composite electrode based on natural
      zeolitic volcanic tuff modified with silver (EG-Ag-Z-Epoxy) was developed. Cyclic
      voltammetry measurements revealed a reasonably fast electron transfer and a good
      stability of the electrode in 0.1 M NaOH supporting electrolyte. This modified
      electrode exhibited moderate electrocatalytic effect towards urea oxidation,
      allowing its determination in aqueous solution. The linear dependence of the
      current versus urea concentration was reached using square-wave voltammetry in
      the concentrations range of urea between 0.2 to 1.4 mM, with a relatively low
      limit of detection of 0.05 mM. A moderate enhancement of electroanalytical
      sensitivity for the determination of urea at EG-Ag-Z-Epoxy electrode was reached
      by applying a chemical preconcentration step prior to voltammetric/amperometric
      quantification.

PMID- 27873842
TI  - Remote Water Temperature Measurements Based on Brillouin Scattering with a
      Frequency Doubled Pulsed Yb:doped Fiber Amplifier.
AB  - Temperature profiles of the ocean are of interest for weather forecasts, climate
      studies and oceanography in general. Currently, mostly in situ techniques such as
      fixed buoys or bathythermographs deliver oceanic temperature profiles. A LIDAR
      method based on Brillouin scattering is an attractive alternative for remote
      sensing of such water temperature profiles. It makes it possible to deliver cost
      effective on-line data covering an extended region of the ocean. The temperature
      measurement is based on spontaneous Brillouin scattering in water. In this
      contribution, we present the first water temperature measurements using a
      Yb:doped pulsed fiber amplifier. The fiber amplifier is a custom designed device
      which can be operated in a vibrational environment while emitting narrow
      bandwidth laser pulses. The device shows promising performance and demonstrates
      the feasibility of this approach. Furthermore, the current status of the receiver
      is briefly discussed; it is based on an excited state Faraday anomalous
      dispersion optical filter.

PMID- 27873843
TI  - A Voltammetric Biosensor Based on Glassy Carbon Electrodes Modified with Single
      Walled Carbon Nanotubes/Hemoglobin for Detection of Acrylamide in Water Extracts
      from Potato Crisps.
AB  - The presence of toxic acrylamide in a wide range of food products such as potato
      crisps, French fries or bread has been confirmed by Swedish scientists from
      Stockholm University. The neurotoxicity, possible carcinogenicity of this
      compound and its metabolites compels us to control them by quantitative and
      qualitative assays. Acrylamide forms adduct with hemoglobin (Hb) as a result of
      the reaction the -NH2 group of the Nterminal valine with acrylamide. In this work
      we present the use of glassy carbon electrodes coated with single-walled carbon
      nanotubes (SWCNTs) and Hb for voltammetric detection of acrylamide in water
      solutions. The electrodes presented a very low detection limit (1.0*10-9 M). The
      validation made in the matrix obtained by water extraction of potato crisps
      showed that the electrodes presented are suitable for the direct determination of
      acrylamide in food samples.

PMID- 27873844
TI  - Fabrication of Pillar Shaped Electrode Arrays for Artificial Retinal Implants.
AB  - Polyimide has been widely applied to neural prosthetic devices, such as the
      retinal implants, due to its well-known biocompatibility and ability to be
      micropatterned. However, planar films of polyimide that are typically employed
      show a limited ability in reducing the distance between electrodes and targeting
      cell layers, which limits site resolution for effective multi-channel
      stimulation. In this paper, we report a newly designed device with a pillar
      structure that more effectively interfaces with the target. Electrode arrays were
      successfully fabricated and safely implanted inside the rabbit eye in
      suprachoroidal space. Optical Coherence Tomography (OCT) showed well-preserved
      pillar structures of the electrode without damage. Bipolar stimulation was
      applied through paired sites (6:1) and the neural responses were successfully
      recorded from several regions in the visual cortex. Electrically evoked cortical
      potential by the pillar electrode array stimulation were compared to visual
      evoked potential under full-field light stimulation.

PMID- 27873845
TI  - Determination of the Content of Heavy Metals in Pyrite Contaminated Soil and
      Plants.
AB  - Determination of a pyrite contaminated soil texture, content of heavy metals in
      the soil and soil pH, was the aim in the investigation. Acidification of damaged
      soil was corrected by calcium carbonate. Mineral nutrients and organic matter
      (NPK, dung, earthworm cast, straw and coal dust) were added to damaged soil.
      Afterwards, the soil was used for oat production. Determination of total heavy
      metal contents (Cu, Pb, Zn, Fe) in soil was performed by atomic absorption
      spectrofotometry. Plant material (stems, seeds ) was analysed, too. Total
      concentration of the heavy metals in the plant material were greater than in crop
      obtained in unaffected soil.

PMID- 27873846
TI  - A New Approach for Structural Monitoring of Large Dams with a Three-Dimensional
      Laser Scanner.
AB  - Driven by progress in sensor technology, computer methods and data processing
      capabilities, 3D laser scanning has found a wide range of new application fields
      in recent years. Particularly, monitoring the static and dynamic behaviour of
      large dams has always been a topic of great importance, due to the impact these
      structures have on the whole landscape where they are built. The main goal of
      this paper is to show the relevance and novelty of the laserscanning methodology
      developed, which incorporates different statistical and modelling approaches not
      considered until now. As a result, the methods proposed in this paper have
      provided the measurement and monitoring of the large "Las Cogotas" dam (Avila,
      Spain).

PMID- 27873847
TI  - Tomographic Imaging of a Forested Area By Airborne Multi-Baseline P-Band SAR.
AB  - In recent years, various attempts have been undertaken to obtain information
      about the structure of forested areas from multi-baseline synthetic aperture
      radar data. Tomographic processing of such data has been demonstrated for
      airborne L-band data but the quality of the focused tomographic images is limited
      by several factors. In particular, the common Fourierbased focusing methods are
      susceptible to irregular and sparse sampling, two problems, that are unavoidable
      in case of multi-pass, multi-baseline SAR data acquired by an airborne system. In
      this paper, a tomographic focusing method based on the time-domain back
      projection algorithm is proposed, which maintains the geometric relationship
      between the original sensor positions and the imaged target and is therefore able
      to cope with irregular sampling without introducing any approximations with
      respect to the geometry. The tomographic focusing quality is assessed by
      analysing the impulse response of simulated point targets and an in-scene corner
      reflector. And, in particular, several tomographic slices of a volume
      representing a forested area are given. The respective P-band tomographic data
      set consisting of eleven flight tracks has been acquired by the airborne E-SAR
      sensor of the German Aerospace Center (DLR).

PMID- 27873848
TI  - Structural Simulation of a Bone-Prosthesis System of the Knee Joint.
AB  - In surgical knee replacement, the damaged knee joint is replaced with artificial
      prostheses. An accurate clinical evaluation must be carried out before applying
      knee prostheses to ensure optimal outcome from surgical operations and to reduce
      the probability of having long-term problems. Useful information can be inferred
      from estimates of the stress acting onto the bone-prosthesis system of the knee
      joint. This information can be exploited to tailor the prosthesis to the
      patient's anatomy. We present a compound system for pre-operative surgical
      planning based on structural simulation of the bone-prosthesis system, exploiting
      patient-specific data.

PMID- 27873849
TI  - Influence of Fluid Cell Design on the Frequency Response of AFM Microcantilevers
      in Liquid Media.
AB  - A study of the frequency response of AFM microcantilevers in liquid media
      contained in a commercial fluid cell is presented. Such systems exhibit
      complicated dynamics which are often not well described by available theories.
      Their dynamic behavior has a direct effect on the use of the AFM in dynamic mode
      while imaging in liquid or while extracting the rheological properties of the
      fluid. We explore the issues related to the design of the cantilever holder/fluid
      cell and propose an approach for evaluating, minimizing and recognizing the
      ultimate limitations of commercial cantilever holders. A technique for estimating
      the frequency response spectrum of the fluid cell itself from experimental data
      is presented. This spectrum can then be used to evaluate whether or not the fluid
      cell is suited for the desired purpose.

PMID- 27873850
TI  - Developments and Applications of Electrogenerated Chemiluminescence Sensors Based
      on Micro- and Nanomaterials.
AB  - A variety of recent developments and applications of electrogenerated
      chemiluminescence (ECL) for sensors are described. While tris(2,2'-bipyridyl)
      ruthenium(II) and luminol have dominated and continue to pervade the field of ECL
      based sensors, recent work has focused on use of these lumophores with micro- and
      nanomaterials. It has also extended to inherently luminescent nanomaterials, such
      as quantum dots. Sensor configurations including microelectrode arrays and
      microfluidics are reviewed and, with the recent trend toward increased use of
      nanomaterials, special attention has been given to sensors which include thin
      films, nanoparticles and nanotubes. Applications of ECL labels and examples of
      label-free sensing that incorporate nanomaterials are also discussed.

PMID- 27873852
TI  - Integrated Evaluation of Urban Development Suitability Based on Remote Sensing
      and GIS Techniques - A Case Study in Jingjinji Area, China.
AB  - Jingjinji area (namely Beijing, Tianjin and He Bei Province) is one of the three
      largest regional economic communities in China. Urban expansion has sped up in
      the past 20 years in this area due to the rapid economic and population growth.
      Evaluating the landuse suitability for urban growth on a regional scale is an
      urgent need, because the most suitable areas and the most suitable scale of urban
      growth can thus be determined accordingly. In order to meet this requirement,
      remote sensing and geographic information system (GIS) techniques were adopted,
      and an integrated evaluating model was developed supported by AHP method. The
      integrated urban development suitability index (UDSI) was calculated using this
      model. According to the UDSI result, the spatial distribution of urban
      development suitability and its driving forces were analyzed. Urban boundaries in
      1995, 2000 and 2005, which were derived from Landsat TM/ETM+ satellite data, were
      overlaid on the UDSI map, and the suitable urban develop tendency in this area
      were discussed. The result of this study indicated that integrated evaluation of
      urban development could be conducted in an operational way using remote sensing
      data, GIS spatial analysis technique and AHP modeling method.

PMID- 27873851
TI  - Color Changes of UHT Milk During Storage.
AB  - In this study measurements of color parameters of UHT milk were performed, by
      using a MOM-color 100 photoelectric tristimulus colorimeter. Colors of UHT milk
      samples containing 3.2% and 1.6% milk fat, processed under industrial conditions,
      packed in polyethylene terephtalate (PET) based packages, and stored for 0, 15,
      30, 45, 60 and 90 days at ambient temperature (20+/-5 degrees C) were examined.
      Results are shown in four different systems that define measurement of color
      parameters expressed in: CIE, CIE L*a*b*, Hunter and ANLAB - Adams Nickerson
      systems. Average value of mean reflectance of UHT milk determined in CIE system
      statistically is highly significantly changed, (p < 0.01) depending on duration
      of storaging, percentage of milk fat, as well as on the interaction of the
      mentioned factors. For the UHT milk with 1.6% milk fat statistically significant
      (p < 0.05) decrease of psychometric chroma b* occurs after 60 days, and for milk
      with 3.2% milk fat established on 45th day of storage.

PMID- 27873853
TI  - Electrochemical Assay of Human Islet Amyloid Polypeptide and Its Aggregation.
AB  - Square wave voltammetry is used in this work to detect human islet amyloid
      polypeptide (hIAPP) by using the oxidized signal of the tyrosine residue in
      hIAPP. A detection limit of 1*10-6 M for hIAPP has been obtained. A kinetic study
      of the aggregation process has been carried out according to the relationship
      between the anodic peak current in the square wave voltammograms of hIAPP and the
      incubation period. The results show that the nucleation starts in the first hour
      of incubation and then, during the next two hours, aggregation may occur rapidly.
      hIAPP can therefore be monitored with a label-free electrochemical method with
      low detection limit and high sensitivity. This electrochemical method can be also
      utilized to study the kinetics of hIAPP aggregation, and it may be also employed
      to study the conformational changes of the polypeptide.

PMID- 27873854
TI  - Programming an Artificial Neural Network Tool for Spatial Interpolation in GIS -
      A Case Study for Indoor Radio Wave Propagation of WLAN.
AB  - Wireless communication networks offer subscribers the possibilities of free
      mobility and access to information anywhere at any time. Therefore,
      electromagnetic coverage calculations are important for wireless mobile
      communication systems, especially in Wireless Local Area Networks (WLANs). Before
      any propagation computation is performed, modeling of indoor radio wave
      propagation needs accurate geographical information in order to avoid the
      interruption of data transmissions. Geographic Information Systems (GIS) and
      spatial interpolation techniques are very efficient for performing indoor radio
      wave propagation modeling. This paper describes the spatial interpolation of
      electromagnetic field measurements using a feed-forward back-propagation neural
      network programmed as a tool in GIS. The accuracy of Artificial Neural Networks
      (ANN) and geostatistical Kriging were compared by adjusting procedures. The
      feedforward back-propagation ANN provides adequate accuracy for spatial
      interpolation, but the predictions of Kriging interpolation are more accurate
      than the selected ANN. The proposed GIS ensures indoor radio wave propagation
      model and electromagnetic coverage, the number, position and transmitter power of
      access points and electromagnetic radiation level. Pollution analysis in a given
      propagation environment was done and it was demonstrated that WLAN (2.4 GHz)
      electromagnetic coverage does not lead to any electromagnetic pollution due to
      the low power levels used. Example interpolated electromagnetic field values for
      WLAN system in a building of Yildiz Technical University, Turkey, were generated
      using the selected network architectures to illustrate the results with an ANN.

PMID- 27873855
TI  - Fabrication of a Novel Conductometric Biosensor for Detecting Mycobacterium avium
      subsp. paratuberculosis Antibodies.
AB  - Johne's disease (JD) is one of the most costly bacterial diseases in cattle. In
      the U.S., economic losses from the disease have been estimated to exceed
      $1,500,000,000 per year, mainly from the effects of reduced milk production.
      Current diagnostic tests for JD are laboratory based and many of those tests
      require specialized equipment and training. Development of rapid and inexpensive
      diagnostic assays, which are adapted for point-ofcare applications, would aid in
      the control of JD. In this study, a polyaniline (Pani)-based conductometric
      biosensor, in an immunomigration format, was fabricated for the detection of
      serum antibody (IgG) against the causal organism of JD, Mycobacterium avium
      subsp. paratuberculosis (MAP). Immobilized Mycobacterium avium purified proteins
      in the capture membrane were used to detect MAP IgG, previously bound with
      Pani/anti-bovine IgG* conjugate in the conjugate membrane. After detection, the
      Pani in the sandwiched captured complex bridges an electrical circuit between the
      silver electrodes, flanking the capture membrane. The electrical conductance,
      caused by Pani, was measured as drop in electrical resistance. Testing of the
      biosensor with known JD positive and negative serum samples demonstrated a
      significant difference in the mean resistance observed between the groups. This
      proof-of-concept study demonstrated that a conductometric biosensor could detect
      MAP IgG in 2 minutes. The biosensor's speed of detection and the equipment
      involved would, among other things, support its application towards the various
      point-ofcare opportunities aimed at JD management and control.

PMID- 27873856
TI  - Surface Heat Balance Analysis of Tainan City on March 6, 2001 Using ASTER and
      Formosat-2 Data.
AB  - The urban heat island phenomenon occurs as a mixed result of anthropogenic heat
      discharge, decreased vegetation, and increased artificial impervious surfaces. To
      clarify the contribution of each factor to the urban heat island, it is necessary
      to evaluate the surface heat balance. Satellite remote sensing data of Tainan
      City, Taiwan, obtained from Terra ASTER and Formosat-2 were used to estimate
      surface heat balance in this study. ASTER data is suitable for analyzing heat
      balance because of the wide spectral range. We used Formosat-2 multispectral data
      to classify the land surface, which was used to interpolate some surface
      parameters for estimating heat fluxes. Because of the high spatial resolution of
      the Formosat-2 image, more roads, open spaces and small vegetation areas could be
      distinguished from buildings in urban areas; however, misclassifications of land
      cover in such areas using ASTER data would overestimate the sensible heat flux.
      On the other hand, the small vegetated areas detected from the Formosat-2 image
      slightly increased the estimation of latent heat flux. As a result, the storage
      heat flux derived from Formosat-2 is higher than that derived from ASTER data in
      most areas. From these results, we can conclude that the higher resolution land
      coverage map increases accuracy of the heat balance analysis. Storage heat flux
      occupies about 60 to 80% of the net radiation in most of the artificial surface
      areas in spite of their usages. Because of the homogeneity of the building roof
      materials, there is no contrast between the storage heat flux in business and
      residential areas. In sparsely vegetated urban areas, more heat is stored and
      latent heat is smaller than that in the forested suburbs. This result implies
      that density of vegetation has a significant influence in decreasing
      temperatures.

PMID- 27873857
TI  - Sensors and Biosensors for the Determination of Small Molecule Biological Toxins.
AB  - The following review of sensors and biosensors focuses on the determination of
      commonly studied small molecule biological toxins, including mycotoxins and small
      molecule neurotoxins. Because of the high toxicity of small molecule toxins, an
      effective analysis technique for determining their toxicity is indispensable.
      Sensors and biosensors have emerged as sensitive and rapid techniques for
      toxicity analysis in the past decade. Several different sensors for the
      determination of mycotoxins and other small molecule neurotoxins have been
      reported in the literature, and many of these sensors such as tissue biosensors,
      enzyme sensors, optical immunosensors, electrochemical sensors, quartz crystal
      sensors, and surface plasmon resonance biosensors are reviewed in this paper.
      Sensors are a practical and convenient monitoring tool in the area of routine
      analysis, and their specificity, sensitivity, reproducibility and analysis
      stability should all be improved in future work. In addition, accuracy field
      portable sensing devices and multiplexing analysis devices will be important
      requirement for the future.

PMID- 27873859
TI  - An Evaluation of Radarsat-1 and ASTER Data for Mapping Veredas (Palm Swamps).
AB  - Veredas (palm swamps) are wetland complexes associated with the Brazilian savanna
      (cerrado) that often represent the only available source of water for the
      ecosystem during the dry months. Their extent and condition are mainly unknown
      and their cartography is an essential issue for their protection. This research
      article evaluates some of the fine resolution satellite data both in the radar
      (Radarsat-1) and optical domain (ASTER) for the delineation and characterization
      of veredas. Two separate approaches are evaluated. First, given the known
      potential of Radarsat-1 images for wetland inventories, the automatic delineation
      of veredas is tested using only Radarsat-1 data and a Markov random fields region
      based segmentation. In this case, to increase performance, processing is limited
      to a buffer zone around the river network. Then, characterization of their type
      is attempted using traditional classification methods of ASTER optical data
      combined with Radarsat-1 data. The automatic classification of Radarsat data
      yielded results with an overall accuracy between 62 and 69%, that proved reliable
      enough for delineating wide and very humid veredas. Scenes from the wet season
      and with a smaller angle of incidence systematically yielded better results. For
      the classification of the main vegetation types, better results (overall success
      of 78.8%) were obtained by using only the visible and near infrared (VNIR) bands
      of the ASTER image. Radarsat data did not bring any improvement to these
      classification results. In fact, when using solely the Radarsat data from two
      different angle of incidence and two different dates, the classification results
      were low (50.8%) but remained powerful for delineating the permanently moist
      riparian forest portion of the veredas with an accuracy better than 75% in most
      cases. These results are considered good given the width of some types often less
      than 50 m wide compared with the resolution of the images (12.5 - 15 m).
      Comparing the classification results with the Radarsat-generated delineation
      allows an understanding of the relation between synthetic aperture radar (SAR)
      backscattering and vegetation types of the veredas.

PMID- 27873860
TI  - Spectral-Based Blind Image Restoration Method for Thin TOMBO Imagers.
AB  - With the recent advances in microelectronic fabrication technology, it becomes
      now possible to fabricate thin imagers, less than half a millimeter thick. Dubbed
      TOMBO (an acronym for thin observation module by bound optics), a thin camera-on
      a-chip integrates micro-optics and photo-sensing elements, together with advanced
      processing circuitry, all on a single silicon chip. Modeled after the compound
      eye found in insects and many other arthropods, the TOMBO imager captures
      simultaneously a mosaic of low resolution images. In this paper, we describe and
      analyze a novel spectral-based blind algorithm that enables the restoration of a
      high resolution image from the captured low resolution images.The proposed blind
      restoration method does not require prior information about the imaging system
      nor the original scene. Furthermore, it alleviates the need for conventional de
      shading and rearrangement processing techniques. Experimental results demonstrate
      that the proposed method can restore images for SNER lower than 3dB.

PMID- 27873861
TI  - Utilization of Electrochemical Sensors and Biosensors in Biochemistry and
      Molecular Biology.
AB  - Editorial note concerning the "Utilization of Electrochemical Sensors and
      Biosensors in Biochemistry and Molecular Biology" special issue.

PMID- 27873862
TI  - Modelling Spatial and Temporal Forest Cover Change Patterns (1973-2020): A Case
      Study from South Western Ghats (India).
AB  - This study used time series remote sensing data from 1973, 1990 and 2004 to
      assess spatial forest cover change patterns in the Kalakad-Mundanthurai Tiger
      Reserve (KMTR), South Western Ghats (India). Analysis of forest cover changes and
      its causes are the most challenging areas of landscape ecology, especially due to
      the absence of temporal ground data and comparable space platform based data.
      Comparing remotely sensed data from three different sources with sensors having
      different spatial and spectral resolution presented a technical challenge.
      Quantitative change analysis over a long period provided a valuable insight into
      forest cover dynamics in this area. Time-series maps were combined within a
      geographical information system (GIS) with biotic and abiotic factors for
      modelling its future change. The land-cover change has been modelled using GEOMOD
      and predicted for year 2020 using the current disturbance scenario. Comparison of
      the forest change maps over the 31-year period shows that evergreen forest being
      degraded (16%) primarily in the form of selective logging and clear felling to
      raise plantations of coffee, tea and cardamom. The natural disturbances such as
      forest fire, wildlife grazing, invasions after clearance and soil erosion induced
      by anthropogenic pressure over the decades are the reasons of forest cover change
      in KMTR. The study demonstrates the role of remote sensing and GIS in monitoring
      of large-coverage of forest area continuously for a given region over time more
      precisely and in cost-effective manner which will be ideal for conservation
      planning and prioritization.

PMID- 27873863
TI  - Fabrication and Optimization of a Nanoporous Platinum Electrode and a Non
      enzymatic Glucose Micro-sensor on Silicon.
AB  - In this paper, optimal conditions for fabrication of nanoporous platinum (Pt)
      were investigated in order to use it as a sensitive sensing electrode for silicon
      CMOS integrable non-enzymatic glucose micro-sensor applications. Applied charges,
      voltages, and temperatures were varied during the electroplating of Pt into the
      formed nonionic surfactant C16EO8 nano-scaled molds in order to fabricate
      nanoporous Pt electrodes with large surface roughness factor (RF), uniformity,
      and reproducibility. The fabricated nanoporous Pt electrodes were characterized
      using atomic force microscopy (AFM) and electrochemical cyclic voltammograms.
      Optimal electroplating conditions were determined to be an applied charge of 35
      mC/mm2, a voltage of -0.12 V, and a temperature of 25  degrees C, respectively.
      The optimized nanoporous Pt electrode had an electrochemical RF of 375 and
      excellent reproducibility. The optimized nanoporous Pt electrode was applied to
      fabricate non-enzymatic glucose micro-sensor with three electrode systems. The
      fabricated sensor had a size of 3 mm x 3 mm, air gap of 10 um, working electrode
      (WE) area of 4.4 mm2, and sensitivity of 37.5 uA*L/mmol*cm2. In addition, it
      showed large detection range from 0.05 to 30 mmolL-1 and stable recovery
      responsive to the step changes in glucose concentration.

PMID- 27873858
TI  - BioMEMS -Advancing the Frontiers of Medicine.
AB  - Biological and medical application of micro-electro-mechanical-systems (MEMS) is
      currently seen as an area of high potential impact. Integration of biology and
      microtechnology has resulted in the development of a number of platforms for
      improving biomedical and pharmaceutical technologies. This review provides a
      general overview of the applications and the opportunities presented by MEMS in
      medicine by classifying these platforms according to their applications in the
      medical field.

PMID- 27873864
TI  - Two Improvements of an Operational Two-Layer Model for Terrestrial Surface Heat
      Flux Retrieval.
AB  - In order to make the prediction of land surface heat fluxes more robust, two
      improvements were made to an operational two-layer model proposed previously by
      Zhang. These improvements are: 1) a surface energy balance method is used to
      determine the theoretical boundary lines (namely 'true wet/cool edge' and 'true
      dry/warm edge' in the trapezoid) in the scatter plot for the surface temperature
      versus the fractional vegetation cover in mixed pixels; 2) a new assumption that
      the slope of the Tm - f curves is mainly controlled by soil water content is
      introduced. The variables required by the improved method include near surface
      vapor pressure, air temperature, surface resistance, aerodynamic resistance,
      fractional vegetation cover, surface temperature and net radiation. The model
      predictions from the improved model were assessed in this study by in situ
      measurements, which show that the total latent heat flux from the soil and
      vegetation are in close agreement with the in situ measurement with an RMSE (Root
      Mean Square Error) ranging from 30 w/m2~50 w/m2,which is consistent with the site
      scale measurement of latent heat flux. Because soil evaporation and vegetation
      transpiration are not measured separately from the field site, in situ measured
      CO2 flux is used to examine the modeled lambdaEveg. Similar trends of seasonal
      variations of vegetation were found for the canopy transpiration retrievals and
      in situ CO2 flux measurements. The above differences are mainly caused by 1) the
      scale disparity between the field measurement and the MODIS observation; 2) the
      non-closure problem of the surface energy balance from the surface fluxes
      observations themselves. The improved method was successfully used to predict the
      component surface heat fluxes from the soil and vegetation and it provides a
      promising approach to study the canopy transpiration and the soil evaporation
      quantitatively during the rapid growing season of winter wheat in northern China.

PMID- 27873865
TI  - Analyzing Land Use/Land Cover Changes Using Remote Sensing and GIS in Rize, North
      East Turkey.
AB  - Mapping land use/land cover (LULC) changes at regional scales is essential for a
      wide range of applications, including landslide, erosion, land planning, global
      warming etc. LULC alterations (based especially on human activities), negatively
      effect the patterns of climate, the patterns of natural hazard and socio-economic
      dynamics in global and local scale. In this study, LULC changes are investigated
      by using of Remote Sensing and Geographic Information Systems (GIS) in Rize,
      North-East Turkey. For this purpose, firstly supervised classification technique
      is applied to Landsat images acquired in 1976 and 2000. Image Classification of
      six reflective bands of two Landsat images is carried out by using maximum
      likelihood method with the aid of ground truth data obtained from aerial images
      dated 1973 and 2002. The second part focused on land use land cover changes by
      using change detection comparison (pixel by pixel). In third part of the study,
      the land cover changes are analyzed according to the topographic structure (slope
      and altitude) by using GIS functions. The results indicate that severe land cover
      changes have occurred in agricultural (36.2%) (especially in tea gardens), urban
      (117%), pasture (-72.8%) and forestry (-12.8%) areas has been experienced in the
      region between 1976 and 2000. It was seen that the LULC changes were mostly
      occurred in coastal areas and in areas having low slope values.

PMID- 27873866
TI  - GACEM: Genetic Algorithm Based Classifier Ensemble in a Multi-sensor System.
AB  - Multi-sensor systems (MSS) have been increasingly applied in pattern
      classification while searching for the optimal classification framework is still
      an open problem. The development of the classifier ensemble seems to provide a
      promising solution. The classifier ensemble is a learning paradigm where many
      classifiers are jointly used to solve a problem, which has been proven an
      effective method for enhancing the classification ability. In this paper, by
      introducing the concept of Meta-feature (MF) and Trans-function (TF) for
      describing the relationship between the nature and the measurement of the
      observed phenomenon, classification in a multi-sensor system can be unified in
      the classifier ensemble framework. Then an approach called Genetic Algorithm
      based Classifier Ensemble in Multi-sensor system (GACEM) is presented, where a
      genetic algorithm is utilized for optimization of both the selection of features
      subset and the decision combination simultaneously. GACEM trains a number of
      classifiers based on different combinations of feature vectors at first and then
      selects the classifiers whose weight is higher than the pre-set threshold to make
      up the ensemble. An empirical study shows that, compared with the conventional
      feature-level voting and decision-level voting, not only can GACEM achieve better
      and more robust performance, but also simplify the system markedly.

PMID- 27873867
TI  - Mesoporous Silicon with Modified Surface for Plant Viruses and Their Protein
      Particle Sensing.
AB  - Changes in electric parameters of a mesoporous silicon treated by a plasma
      chemical etching with fluorine and hydrogen ions, under the adsorption of NEPO
      (Nematodetransmitted Polyhedral) plant viruses such as TORSV (Tomato Ringspot
      Virus), GFLV (Grapevine Fan Leaf Virus) and protein macromolecule from TORSV
      particles are described. The current response to the applied voltage is measured
      for each virus particle to investigate the material parameters which are
      sensitive to the adsorbed particles. The peculiar behaviors of the response are
      modeled by the current-voltage relationship in a MOSFET. This model explains the
      behavior well and the double gate model of the MOSFET informs that the mesoporous
      silicon is a highly sensitive means of detecting the viruses in the size range
      less than 50 nm.

PMID- 27873868
TI  - APEX - the Hyperspectral ESA Airborne Prism Experiment.
AB  - The airborne ESA-APEX (Airborne Prism Experiment) hyperspectral mission simulator
      is described with its distinct specifications to provide high quality remote
      sensing data. The concept of an automatic calibration, performed in the
      Calibration Home Base (CHB) by using the Control Test Master (CTM), the In-Flight
      Calibration facility (IFC), quality flagging (QF) and specific processing in a
      dedicated Processing and Archiving Facility (PAF), and vicarious calibration
      experiments are presented. A preview on major applications and the corresponding
      development efforts to provide scientific data products up to level 2/3 to the
      user is presented for limnology, vegetation, aerosols, general classification
      routines and rapid mapping tasks. BRDF (Bidirectional Reflectance Distribution
      Function) issues are discussed and the spectral database SPECCHIO (Spectral
      Input/Output) introduced. The optical performance as well as the dedicated
      software utilities make APEX a state-of-the-art hyperspectral sensor, capable of
      (a) satisfying the needs of several research communities and (b) helping the
      understanding of the Earth's complex mechanisms.

PMID- 27873869
TI  - A New Method to Define the VI-Ts Diagram Using Subpixel Vegetation and Soil
      Information: A Case Study over a Semiarid Agricultural Region in the North China
      Plain.
AB  - The VI-Ts diagram determined by the scatter points of the vegetation index (VI)
      and surface temperature (Ts) has been widely applied in land surface studies. In
      the VI-Ts diagram, dry point is defined as a pixel with maximum Ts and minimum
      VI, while wet point is defined as a pixel with minimum Ts and maximum VI. If both
      dry and wet points can be obtained simultaneously, a triangular VI-Ts diagram can
      be readily defined. However, traditional methods cannot define an ideal VI-Ts
      diagram if there are no full ranges of land surface moisture and VI, such as
      during rainy season or in a period with a narrow VI range. In this study, a new
      method was proposed to define the VI-Ts diagram based on the subpixel vegetation
      and soil information, which was independent of the full ranges of land surface
      moisture and VI. In this method, a simple approach was firstly proposed to
      decompose Ts of a given pixel into two components, the surface temperatures of
      soil (Tsoil) and vegetation (Tveg), by means of Ts and VI information of
      neighboring pixels. The minimum Tveg and maximum Tsoil were then used to
      determine the wet and dry points respectively within a given sampling window.
      This method was tested over a 30 km * 30 km semiarid agricultural area in the
      North China Plain through 2003 using Advanced Spaceborne Thermal Emission
      Reflection Radiometer (ASTER) and MODerate-resolution Imaging Spectroradiometer
      (MODIS) data. The wet and dry points obtained from our proposed method and from a
      traditional method were compared with those obtained from ground data within the
      sampling window with the 30 km * 30 km size. Results show that Tsoil and Tveg can
      be obtained with acceptable accuracies, and that our proposed method can define
      reasonable VI-Ts diagrams over a semiarid agricultural region throughout the
      whole year, even for both cases of rainy season and narrow range of VI.

PMID- 27873870
TI  - Crime Scene Reconstruction Using a Fully Geomatic Approach.
AB  - This paper is focused on two main topics: crime scene reconstruction, based on a
      geomatic approach, and crime scene analysis, through GIS based procedures.
      According to the experience of the authors in performing forensic analysis for
      real cases, the aforesaid topics will be examined with the specific goal of
      verifying the relationship of human walk paths at a crime scene with blood
      patterns on the floor. In order to perform such analyses, the availability of
      pictures taken by first aiders is mandatory, since they provide information about
      the crime scene before items are moved or interfered with. Generally, those
      pictures are affected by large geometric distortions, thus - after a brief
      description of the geomatic techniques suitable for the acquisition of reference
      data (total station surveying, photogrammetry and laser scanning) - it will be
      shown the developed methodology, based on photogrammetric algorithms, aimed at
      calibrating, georeferencing and mosaicking the available images acquired on the
      scene. The crime scene analysis is based on a collection of GIS functionalities
      for simulating human walk movements and creating a statistically significant
      sample. The developed GIS software component will be described in detail, showing
      how the analysis of this statistical sample of simulated human walks allows to
      rigorously define the probability of performing a certain walk path without
      touching the bloodstains on the floor.

PMID- 27873872
TI  - A Multivariate Model for Coastal Water Quality Mapping Using Satellite Remote
      Sensing Images.
AB  - his study demonstrates the feasibility of coastal water quality mapping using
      satellite remote sensing images. Water quality sampling campaigns were conducted
      over a coastal area in northern Taiwan for measurements of three water quality
      variables including Secchi disk depth, turbidity, and total suspended solids.
      SPOT satellite images nearly concurrent with the water quality sampling campaigns
      were also acquired. A spectral reflectance estimation scheme proposed in this
      study was applied to SPOT multispectral images for estimation of the sea surface
      reflectance. Two models, univariate and multivariate, for water quality
      estimation using the sea surface reflectance derived from SPOT images were
      established. The multivariate model takes into consideration the wavelength
      dependent combined effect of individual seawater constituents on the sea surface
      reflectance and is superior over the univariate model. Finally, quantitative
      coastal water quality mapping was accomplished by substituting the pixel-specific
      spectral reflectance into the multivariate water quality estimation model.

PMID- 27873871
TI  - First Contact to Odors: Our Current Knowledge about Odorant Receptor.
AB  - Chemical senses - especially smell - are known to be important for the
      fundamental life events such as sensing predators, selecting mates, as well as
      finding food. The chemical senses are decoded in the olfactory system which is
      able to detect and differentiate thousands of odorous substances comprised of
      chemically divergent structures (i.e. odorants). The high selectivity of the
      olfactory system is heavily dependent on the receptors for each odorants (i.e.
      odorant receptors). Thus, studying odorant receptors may not only facilitate our
      understanding the initial events of olfaction but provide crucial knowledge for
      developing a novel, odorant receptor-based biosensor for chemical screening. Here
      we provide a review of recent advances in our understanding of odorant receptors.

PMID- 27873873
TI  - Thin Film on CMOS Active Pixel Sensor for Space Applications.
AB  - A 664 x 664 element Active Pixel image Sensor (APS) with integrated analog signal
      processing, full frame synchronous shutter and random access for applications in
      star sensors is presented and discussed. A thick vertical diode array in Thin
      Film on CMOS (TFC) technology is explored to achieve radiation hardness and
      maximum fill factor.

PMID- 27873874
TI  - Room Temperature Ammonia Gas Sensing Using Mixed Conductor based TEMPOS
      Structures.
AB  - The current/voltage characteristics of mixed (ion+electron) conductor-based
      'TEMPOS' (Tunable Electronic Material with Pores in Oxide on Silicon) structures
      are reported. TEMPOS are novel electronic MOS-like structures having etched swift
      heavy ion tracks (i.e., nanopores) in the dielectric layer filled with some
      conducting material. The three contacts (two on top and one on the bottom), which
      resemble the classical bipolar or field effect transistor arrangements are, in
      principle, interchangeable when the overall electrical resistance along the
      tracks and on the surface are similar. Consequently, three configurations are
      obtained by interchanging the top contacts with the base contact in electronic
      circuits. The current/voltage characteristics show a diode like behaviour.
      Impedance measurements have been made for TEMPOS structures with tracks filled
      with ion conductors and also mixed conductors to study the ammonia sensing
      behaviour. The impedance has been found to be a function of frequency and
      magnitude of the applied signal and concentration of the ammonia solution. This
      is attributed to the large number of charge carriers (here protons) available for
      conduction on exposure to ammonia and also to the large surface to volume ratio
      of the polymer composites embedded in the ion tracks. The measurement of both,
      the real and imaginary parts of impedance allows one to enhance the detection
      sensitivity greatly.

PMID- 27873875
TI  - Mining the Urban Sprawl Pattern: A Case Study on Sunan, China.
AB  - China's urbanization is going into a fast development stage. This paper focuses
      on the recent evolution of an urbanized area - Sunan, the southern part of
      Jiangsu province in the Yangtze River Delta in China - by means of complementary
      approaches, especially different fractal and autocorrelation measures. The
      research shows that Sunan's urban clusters are becoming more and more homogenous
      and compact and are growing up along the important transportation axes. The
      enriching discussion of the findings establishes the links between the morphology
      of urban sprawl and recent socio-economic changes in China.

PMID- 27873876
TI  - Effects of Gold Nanoparticles on the Response of Phenol Biosensor Containing
      Photocurable Membrane with Tyrosinase.
AB  - The role of incorporation of gold nanoparticles (50-130 nm in diameter) into a
      series of photocurable methacrylic-acrylic based biosensor membranes containing
      tyrosinase on the response for phenol detection was investigated. Membranes with
      different hydrophilicities were prepared from 2-hydroxyethyl methacrylate and n
      butyl acrylate via direct photocuring. A range of gold nanoparticles
      concentrations from 0.01 to 0.5 % (w/w) was incorporated into these membranes
      during the photocuring process. The addition of gold nanoparticles to the
      biosensor membrane led to improvement in the response time by a reduction of
      approximately 5 folds to give response times of 5-10 s. The linear response range
      of the phenol biosensor was also extended from 24 to 90 mM of phenol. The
      hydrophilicities of the membrane matrices demonstrated strong influence on the
      biosensor response and appeared to control the effect of the gold nanoparticles.
      For less hydrophilic methacrylic-acrylic membranes, the addition of gold
      nanoparticles led to a poorer sensitivity and detection limit of the biosensor
      towards phenol. Therefore, for the application of gold nanoparticles in the
      enhancement of a phenol biosensor response, the nanoparticles should be
      immobilized in a hydrophilic matrix rather than a hydrophobic material.

PMID- 27873877
TI  - Development of Light Powered Sensor Networks for Thermal Comfort Measurement.
AB  - Recent technological advances in wireless communications have enabled easy
      installation of sensor networks with air conditioning equipment control
      applications. However, the sensor node power supply, through either power lines
      or battery power, still presents obstacles to the distribution of the sensing
      systems. In this study, a novel sensor network, powered by the artificial light,
      was constructed to achieve wireless power transfer and wireless data
      communications for thermal comfort measurements. The sensing node integrates an
      IC-based temperature sensor, a radiation thermometer, a relative humidity sensor,
      a micro machined flow sensor and a microprocessor for predicting mean vote (PMV)
      calculation. The 935 MHz band RF module was employed for the wireless data
      communication with a specific protocol based on a special energy beacon enabled
      mode capable of achieving zero power consumption during the inactive periods of
      the nodes. A 5W spotlight, with a dual axis tilt platform, can power the
      distributed nodes over a distance of up to 5 meters. A special algorithm, the
      maximum entropy method, was developed to estimate the sensing quantity of climate
      parameters if the communication module did not receive any response from the
      distributed nodes within a certain time limit. The light-powered sensor networks
      were able to gather indoor comfort-sensing index levels in good agreement with
      the comfort-sensing vote (CSV) preferred by a human being and the experimental
      results within the environment suggested that the sensing system could be used in
      air conditioning systems to implement a comfort-optimal control strategy.

PMID- 27873878
TI  - Real-time Monitoring of Non-specific Toxicity Using a Saccharomyces cerevisiae
      Reporter System.
AB  - Baker's yeast, Saccharomyces cerevisiae, is the simplest and most well-known
      representative of eukaryotic cells and thus a convenient model organism for
      evaluating toxic effects in human cells and tissues. Yeast cell sensors are easy
      to maintain with short generation times, which makes the analytical method of
      assessing antifungal toxicity cheap and less-time consuming. In this work, the
      toxicity of test compounds was assessed in bioassays based on bioluminescence
      inhibition and on traditional growth inhibition on agar plates. The model
      organism in both tests was a modified S. cerevisiae sensor strain that produces
      light when provided with D-luciferin in an insect luciferase reporter gene
      activity assay. The bioluminescence assay showed toxic effects for yeast cell
      sensor of 5,6-benzo-flavone, rapamycin, nystatin and cycloheximide at
      concentrations of nM to uM. In addition, arsenic compounds, cadmium chloride,
      copper sulfate and lead acetate were shown to be potent non-specific inhibitors
      of the reporter organism described here. The results from a yeast agar diffusion
      assay correlated with the bioluminescence assay results.

PMID- 27873879
TI  - Extreme Silica Optical Fibre Gratings.
AB  - A regenerated optical fibre Bragg grating that survives temperature cycling up to
      1,295 degrees C is demonstrated. A model based on seeded crystallisation or
      amorphisation is proposed.

PMID- 27873880
TI  - Detection of Staphylococcus epidermidis by a Quartz Crystal Microbalance Nucleic
      Acid Biosensor Array Using Au Nanoparticle Signal Amplification.
AB  - Staphylococcus epidermidis is a critical pathogen of nosocomial blood infections,
      resulting in significant morbidity and mortality. A piezoelectric quartz crystal
      microbalance (QCM) nucleic acid biosensor array using Au nanoparticle signal
      amplification was developed to rapidly detect S. epidermidis in clinical samples.
      The synthesized thiolated probes specific targeting S. epidermidis 16S rRNA gene
      were immobilized on the surface of QCM nucleic acid biosensor arrays.
      Hybridization was induced by exposing the immobilized probes to the PCR amplified
      fragments of S. epidermidis, resulting in a mass change and a consequent
      frequency shift of the QCM biosensor. To further enhance frequency shift results
      from above described hybridizations, streptavidin coated Au nanoparticles were
      conjugated to the PCR amplified fragments. The results showed that the lowest
      detection limit of current QCM system was 1.3*103 CFU/mL. A linear correlation
      was found when the concentration of S. epidermidis varied from 1.3*103 to 1.3*107
      CFU/mL. In addition, 55 clinical samples were detected with both current QCM
      biosensor system and conventional clinical microbiological method, and the
      sensitivity and specificity of current QCM biosensor system were 97.14% and 100%,
      respectively. In conclusion, the current QCM system is a rapid, low-cost and
      sensitive method that can be used to identify infection of S. epidermidis in
      clinical samples.

PMID- 27873882
TI  - Two-dimensional Co-Seismic Surface Displacements Field of the Chi-Chi Earthquake
      Inferred from SAR Image Matching.
AB  - The Mw=7.6 Chi-Chi earthquake in Taiwan occurred in 1999 over the Chelungpu fault
      and caused a great surface rupture and severe damage. Differential Synthetic
      Aperture Radar Interferometry (DInSAR) has been applied previously to study the
      co-seismic ground displacements. There have however been significant limitations
      in the studies. First, only one-dimensional displacements along the Line-of-Sight
      (LOS) direction have been measured. The large horizontal displacements along the
      Chelungpu fault are largely missing from the measurements as the fault is nearly
      perpendicular to the LOS direction. Second, due to severe signal decorrelation on
      the hangling wall of the fault, the displacements in that area are un-measurable
      by differential InSAR method. We estimate the co-seismic displacements in both
      the azimuth and range directions with the method of SAR amplitude image matching.
      GPS observations at the 10 GPS stations are used to correct for the orbital ramp
      in the amplitude matching and to create the two-dimensional (2D) co-seismic
      surface displacements field using the descending ERS-2 SAR image pair. The
      results show that the co-seismic displacements range from about -2.0 m to 0.7 m
      in the azimuth direction (with the positive direction pointing to the flight
      direction), with the footwall side of the fault moving mainly southwards and the
      hanging wall side northwards. The displacements in the LOS direction range from
      about -0.5 m to 1.0 m, with the largest displacement occuring in the northeastern
      part of the hanging wall (the positive direction points to the satellite from
      ground). Comparing the results from amplitude matching with those from DInSAR, we
      can see that while only a very small fraction of the LOS displacement has been
      recovered by the DInSAR mehtod, the azimuth displacements cannot be well detected
      with the DInSAR measurements as they are almost perpendicular to the LOS.
      Therefore, the amplitude matching method is obviously more advantageous than the
      DInSAR in studying the Chi-Chi earthquake. Another advantage of the method is
      that the displacement in the hanging wall of the fault that is un-measurable with
      DInSAR due to severe signal decorrelation can almost completely retrieved in this
      research. This makes the whole co-seismic displacements field clearly visible and
      the location of the rupture identifiable. Using displacements measured at 15
      independent GPS stations for validation, we found that the RMS values of the
      differences between the two types of results were 6.9 cm and 5.7 cm respectively
      in the azimuth and the range directions.

PMID- 27873881
TI  - Effect of the Temperature-Emissivity Contrast on the Chemical Signal for Gas
      Plume Detection Using Thermal Image Data.
AB  - Detecting and identifying weak gaseous plumes using thermal imaging data is
      complicated by many factors. These include variability due to atmosphere, ground
      and plume temperature, and background clutter. This paper presents an analysis of
      one formulation of the physics-based radiance model, which describes at-sensor
      observed radiance. The background emissivity and plume/ground temperatures are
      isolated, and their effects on chemical signal are described. This analysis shows
      that the plume's physical state, emission or absorption, is directly dependent on
      the background emissivity and plume/ground temperatures. It then describes what
      conditions on the background emissivity and plume/ground temperatures have
      inhibiting or amplifying effects on the chemical signal. These claims are
      illustrated by analyzing synthetic hyperspectral imaging data with the adaptive
      matched filter using two chemicals and three distinct background emissivities.

PMID- 27873883
TI  - Arc-Welding Spectroscopic Monitoring based on Feature Selection and Neural
      Networks.
AB  - A new spectral processing technique designed for application in the on-line
      detection and classification of arc-welding defects is presented in this paper. A
      noninvasive fiber sensor embedded within a TIG torch collects the plasma
      radiation originated during the welding process. The spectral information is then
      processed in two consecutive stages. A compression algorithm is first applied to
      the data, allowing real-time analysis. The selected spectral bands are then used
      to feed a classification algorithm, which will be demonstrated to provide an
      efficient weld defect detection and classification. The results obtained with the
      proposed technique are compared to a similar processing scheme presented in
      previous works, giving rise to an improvement in the performance of the
      monitoring system.

PMID- 27873884
TI  - Characterization of Laser Cleaning of Artworks.
AB  - The main tasks of conservators of artworks and monuments are the estimation and
      analysis of damages (present condition), object conservation (cleaning process),
      and the protection of an object against further degradation. One of the physical
      methods that is becoming more and more popular for dirt removal is the laser
      cleaning method. This method is non-contact, selective, local, controlled, self
      limiting, gives immediate feedback and preserves even the gentlest of relief -
      the trace of a paintbrush. Paper presents application of different, selected
      physical sensing methods to characterize condition of works of art as well as
      laser cleaning process itself. It includes, tested in our laboratories, optical
      surface measurements (e.g. colorimetry, scatterometry, interferometry), infrared
      thermography, optical coherent tomography and acoustic measurements for "on-line"
      evaluation of cleaning progress. Results of laser spectrometry analyses (LIBS,
      Raman) will illustrate identification and dating of objects superficial layers.

PMID- 27873885
TI  - Porous Silicon Based Resonant Mirrors for Biochemical Sensing.
AB  - We report on our preliminary results in the realization and characterization of a
      porous silicon (PSi) resonant mirror (RM) for optical biosensing. We have
      numerically and experimentally studied the coupling between the electromagnetic
      field, totally reflected at the base of a high refractive index prism, and the
      optical modes of a PSi waveguide. This configuration is very sensitive to changes
      in the refractive index and/or in thickness of the sensor surface. Due to the
      high specific area of the PSi waveguide, very low DNA concentrations can be
      detected confirming that the RM could be a very sensitive and labelfree optical
      biosensor.

PMID- 27873886
TI  - Pre-Launch Absolute Calibration of CCD/CBERS-2B Sensor.
AB  - Pre-launch absolute calibration coefficients for the CCD/CBERS-2B sensor have
      been calculated from radiometric measurements performed in a satellite
      integration and test hall in the Chinese Academy of Space Technology (CAST)
      headquarters, located in Beijing, China. An illuminated integrating sphere was
      positioned in the test hall facilities to allow the CCD/CBERS-2B imagery of the
      entire sphere aperture. Calibration images were recorded and a relative
      calibration procedure adopted exclusively in Brazil was applied to equalize the
      detectors responses. Averages of digital numbers (DN) from these images were
      determined and correlated to their respective radiance levels in order to
      calculate the absolute calibration coefficients. It has been the first time these
      pre-launch absolute calibration coefficients have been calculated considering the
      Brazilian image processing criteria. Now it will be possible to compare them to
      those that will be calculated from vicarious calibration campaigns. This
      comparison will permit the CCD/CBERS-2B monitoring and the frequently data
      updating to the user community.

PMID- 27873887
TI  - A Review of the CMOS Buried Double Junction (BDJ) Photodetector and its
      Applications.
AB  - A CMOS Buried Double Junction PN (BDJ) photodetector consists of two vertically
      stacked photodiodes. It can be operated as a photodiode with improved performance
      and wavelength-sensitive response. This paper presents a review of this device
      and its applications. The CMOS implementation and operating principle are firstly
      described. This includes the description of several key aspects directly related
      to the device performances, such as surface reflection, photon absorption and
      electron-hole pair generation, photocurrent and dark current generation, etc.
      SPICE modelling of the detector is then presented. Next, design and process
      considerations are proposed in order to improve the BDJ performance. Finally,
      several BDJ-detector-based image sensors provide a survey of their applications.

PMID- 27873888
TI  - Femtosecond Laser Microfabrication of an Integrated Device for Optical Release
      and Sensing of Bioactive Compounds.
AB  - Flash photolysis of caged compounds is one of the most powerful approaches to
      investigate the dynamic response of living cells. Monolithically integrated
      devices suitable for optical uncaging are in great demand since they greatly
      simplify the experiments and allow their automation. Here we demonstrate the
      fabrication of an integrated bio-photonic device for the optical release of caged
      compounds. Such a device is fabricated using femtosecond laser micromachining of
      a glass substrate. More in detail, femtosecond lasers are used both to cut the
      substrate in order to create a pit for cell growth and to inscribe optical
      waveguides for spatially selective uncaging of the compounds present in the
      culture medium. The operation of this monolithic bio-photonic device is tested
      using both free and caged fluorescent compounds to probe its capability of
      multipoint release and optical sensing. Application of this device to the study
      of neuronal network activity can be envisaged.

PMID- 27873890
TI  - Oil Spill Detection by SAR Images: Dark Formation Detection, Feature Extraction
      and Classification Algorithms.
AB  - This paper provides a comprehensive review of the use of Synthetic Aperture Radar
      images (SAR) for detection of illegal discharges from ships. It summarizes the
      current state of the art, covering operational and research aspects of the
      application. Oil spills are seriously affecting the marine ecosystem and cause
      political and scientific concern since they seriously effect fragile marine and
      coastal ecosystem. The amount of pollutant discharges and associated effects on
      the marine environment are important parameters in evaluating sea water quality.
      Satellite images can improve the possibilities for the detection of oil spills as
      they cover large areas and offer an economical and easier way of continuous coast
      areas patrolling. SAR images have been widely used for oil spill detection. The
      present paper gives an overview of the methodologies used to detect oil spills on
      the radar images. In particular we concentrate on the use of the manual and
      automatic approaches to distinguish oil spills from other natural phenomena. We
      discuss the most common techniques to detect dark formations on the SAR images,
      the features which are extracted from the detected dark formations and the most
      used classifiers. Finally we conclude with discussion of suggestions for further
      research. The references throughout the review can serve as starting point for
      more intensive studies on the subject.

PMID- 27873889
TI  - Molecular Recognition and Specific Interactions for Biosensing Applications.
AB  - Molecular recognition and specific interactions are reliable and versatile routes
      for site-specific and well-oriented immobilization of functional biomolecules on
      surfaces. The control of surface properties via the molecular recognition and
      specific interactions at the nanoscale is a key element for the nanofabrication
      of biosensors with high sensitivity and specificity. This review intends to
      provide a comprehensive understanding of the molecular recognition- and specific
      interaction-mediated biosensor fabrication routes that leads to biosensors with
      well-ordered and controlled structures on both nanopatterned surfaces and
      nanomaterials. Herein self-assembly of the biomolecules via the molecular
      recognition and specific interactions on nanoscaled surfaces as well as
      nanofabrication techniques of the biomolecules for biosensor architecture are
      discussed. We also describe the detection of molecular recognition- and specific
      interaction-mediated molecular binding as well as advantages of nanoscale
      detection.

PMID- 27873892
TI  - Impact of Link Unreliability and Asymmetry on the Quality of Connectivity in
      Large-scale Sensor Networks.
AB  - Connectivity is a fundamental issue in research on wireless sensor networks.
      However, unreliable and asymmetric links have a great impact on the global
      quality of connectivity (QoC). By assuming the deployment of nodes a homogeneous
      Poisson point process and eliminating the border effect, this paper derives an
      explicit expression of node non-isolation probability as the upper bound of one
      connectivity, based on an analytical link model which incorporates important
      parameters such as path loss exponent, shadowing variance of channel, modulation,
      encoding method etc. The derivation has built a bridge over the local link
      property and the global network connectivity, which makes it clear to see how
      various parameter impact the QoC. Numerical results obtained further confirm the
      analysis and can be used as reference for practical design and simulation of
      wireless ad hoc and sensor networks. Besides, we find giant component size a good
      relaxed measure of connectivity in some applications that do not require full
      connectivity.

PMID- 27873891
TI  - Surface-Modified Gold Nanoparticles with Folic Acid as Optical Probes for
      Cellular Imaging.
AB  - In this study, we demonstrate that the uptake rate of the surface-modified gold
      nanoparticles (GNPs) with folic acid by specific cells can be increased
      significantly, if the membranes of these cells have sufficient folic-acid
      receptors. Two human breast cancer cell lines were studied; one is MDA-MB-435S
      cell, and the other T-47D cell. The expression of the folic acid receptors of the
      former is much higher than that of the latter. These cells were incubated with
      media containing bare GNPs or GNPs conjugated with folic acid individually. Due
      to the unique optical behavior (i.e. surface plasmon resonance) of GNPs, the
      uptake amount of GNPs by cells can be identified by using the laser scanning
      confocal microscopy. Our experiments show that the uptake amount of GNPs in MDAMB
      435S cells is higher than that in T-47D cells for the same culture time, if the
      culture medium contains bare GNPs. Moreover, if the GNPs conjugated with folic
      acid are used for the culture, the uptake rate of GNPs by MDA-MB-435S cells is
      improved more. In contrast, the uptake rates of both GNPs are almost the same by
      T-47D cells. The phenomenon indicates that the uptake rate of GNPs can be
      improved via the ligand-receptor endocytosis, compared with the nonspecific
      endocytosis. Therefore, the uptake rate of GNPs conjugated with folic acid by MDA
      MB-435S cells is higher than that of bare GNPs.

PMID- 27873893
TI  - Comparative and Combinative Study of Urban Heat island in Wuhan City with Remote
      Sensing and CFD Simulation.
AB  - Urban heat islands are one of the most critical urban environment heat problems.
      Landsat ETM+ satellite data were used to investigate the land surface temperature
      and underlying surface indices such as NDVI and NDBI. A comparative study of the
      urban heat environment at different scales, times and locations was done to
      verify the heat island characteristics. Since remote sensing technology has
      limitations for dynamic flow analysis in the study of urban spaces, a CFD
      simulation was used to validate the improvement of the heat environment in a city
      by means of wind. CFD technology has its own shortcomings in parameter setting
      and verification, while RS technology is helpful to remedy this. The city of
      Wuhan and its climatological condition of being hot in summer and cold in winter
      were chosen to verify the comparative and combinative application of RS with CFD
      in studying the urban heat island.

PMID- 27873895
TI  - Immunoglobulin G Determination in Human Serum and Milk Using an Immunosensor of
      New Conception Fitted with an Enzyme Probe as Transducer.
AB  - To completely overcome the problem of the presence of urea in the serum, which
      can be the cause (especially at low immunoglobulin G concentrations) of a small
      but non negligible interference in the enzyme reaction of the enzymatic marker,
      when the measurement was performed by a potentiometric immunosensor that we
      constructed and characterized in previous work, and which used urease as marker,
      we have now constructed an entirely different and highly innovative immunosensor.
      This new device uses the enzyme alkaline phosphatase as marker, sodium
      phenylphosphate as substrate but above all, a tyrosinase biosensor obtained by
      coupling a Clark type gas diffusion amperometric electrode and the tyrosinase
      enzyme, immobilized in a cellulose triacetate membrane, as transducer. After
      optimizing the 'competitive' measurement procedures, the new immunosensor was
      used to determine both HIgG and the anti-HIgG, with a limit of detection (LOD) of
      the order of 3x10-11 M. Clearly this highly innovative construction geometry
      makes the immunosensor extremely selective. This makes it possible to determine
      immunoglobulin G both in human serum and milk without the slightest interference
      by any urea present in these biological matrixes.

PMID- 27873894
TI  - NeuroMEMS: Neural Probe Microtechnologies.
AB  - Neural probe technologies have already had a significant positive effect on our
      understanding of the brain by revealing the functioning of networks of biological
      neurons. Probes are implanted in different areas of the brain to record and/or
      stimulate specific sites in the brain. Neural probes are currently used in many
      clinical settings for diagnosis of brain diseases such as seizers, epilepsy,
      migraine, Alzheimer's, and dementia. We find these devices assisting paralyzed
      patients by allowing them to operate computers or robots using their neural
      activity. In recent years, probe technologies were assisted by rapid advancements
      in microfabrication and microelectronic technologies and thus are enabling highly
      functional and robust neural probes which are opening new and exciting avenues in
      neural sciences and brain machine interfaces. With a wide variety of probes that
      have been designed, fabricated, and tested to date, this review aims to provide
      an overview of the advances and recent progress in the microfabrication
      techniques of neural probes. In addition, we aim to highlight the challenges
      faced in developing and implementing ultralong multi-site recording probes that
      are needed to monitor neural activity from deeper regions in the brain. Finally,
      we review techniques that can improve the biocompatibility of the neural probes
      to minimize the immune response and encourage neural growth around the electrodes
      for long term implantation studies.

PMID- 27873896
TI  - Modeling of an Optical Sensor Based on Whispering Gallery Modes (WGMs) on the
      Surface Guiding Layer of Glass Filaments.
AB  - A ring-resonator-based refractive index sensor is proposed in this paper. Glass
      filaments with surface guiding layers created by ion exchange are crossed with a
      fiber taper to act as a ring resonator sensor. Theoretical simulation of the
      sensor response is proposed, and optimization of structural parameters including
      thickness and refractive index of the surface guiding layer and the diameter of
      the ring resonator for higher sensitivity is investigated. Results show that a
      detection limit of a variation of ~10-5RIU can be reached. Due to its simple
      fabrication and easy manipulation as well as good sensing performance, we believe
      such a micro-cavity sensor will find potential applications in high sensitivity
      optical sensing.

PMID- 27873897
TI  - Optimization of Single-Sensor Two-State Hot-Wire Anemometer Transmission
      Bandwidth.
AB  - Hot-wire anemometric measurements of non-isothermal flows require the use of
      thermal compensation or correction circuitry. One possible solution is a two
      state hot-wire anemometer that uses the cyclically changing heating level of a
      single sensor. The area in which flow velocity and fluid temperature can be
      measured is limited by the dimensions of the sensor's active element. The system
      is designed to measure flows characterized by high velocity and temperature
      gradients, although its transmission bandwidth is very limited. In this study, we
      propose a method to optimize the two-state hot-wire anemometer transmission
      bandwidth. The method is based on the use of a specialized constanttemperature
      system together with variable dynamic parameters. It is also based on a suitable
      measurement cycle paradigm. Analysis of the method was undertaken using model
      testing. Our results reveal a possible significant broadening of the two-state
      hot-wire anemometer's transmission bandwidth.

PMID- 27873898
TI  - Linear FBG Temperature Sensor Interrogation with Fabry-Perot ITU Multi-wavelength
      Reference.
AB  - The equidistantly spaced multi-passbands of a Fabry-Perot ITU filter are used as
      an efficient multi-wavelength reference for fiber Bragg grating sensor
      demodulation. To compensate for the nonlinear wavelength tuning effect in the FBG
      sensor demodulator, a polynomial fitting algorithm was applied to the temporal
      peaks of the wavelength-scanned ITU filter. The fitted wavelength values are
      assigned to the peak locations of the FBG sensor reflections, obtaining constant
      accuracy, regardless of the wavelength scan range and frequency. A linearity
      error of about 0.18% against a reference thermocouple thermometer was obtained
      with the suggested method.

PMID- 27873899
TI  - Interfacial Recognition of Acetylcholine by an Amphiphilic p
      Sulfonatocalix[8]arene Derivative Incorporated into Dimyristoyl
      Phosphatidylcholine Vesicles.
AB  - Dodecyl ether derivatives 1-3 of p-sulfonatocalix[n]arene were incorporated into
      dimyristoyl phosphatidylcholine (DMPC) vesicles, and their binding abilities for
      acetylcholine (ACh) were examined by using steady-state fluorescence/fluorescence
      anisotropy and fluorescence correlation spectroscopy (FCS). For the detection of
      ACh binding to the DMPC vesicles containing 5 mol % of 1-3, competitive
      fluorophore displacement experiments were performed, where rhodamine 6G (Rh6G)
      was used as a fluorescent guest. The addition of Rh6G to the DMPC vesicles
      containing 3 resulted in a decrease in the fluorescence intensity of Rh6G with an
      increase of its fluorescence anisotropy, indicating that Rh6G binds to the DMPC-3
      vesicles. In the case of DMPC-1 and DMPC-2 vesicles, significant changes in the
      fluorescence spectra of Rh6G were not observed. When ACh was added to the DMPC-3
      vesicles in the presence of Rh6G ([3]/[Rh6G]=100), the fluorescence intensity of
      Rh6G increased with a decrease in its fluorescence anisotropy. From the analysis
      of fluorescence titration data, the association constants were determined to be
      7.1*105 M-1 for Rh6G-3 complex and 1.1*102 M-1 for ACh-3 complex at the DMPC-3
      vesicles. To get a direct evidence for the binding of Rh6G and its displacement
      by ACh at the DMPC-3 vesicles, diffusion times of the Rh6G were measured by using
      FCS. Binding selectivity of the DMPC-3 vesicles for ACh, choline, GABA, L
      aspartic acid, L-glutamic acid, L-arginine, L-lysine, L-histamine and ammonium
      chloride was also evaluated using FCS.

PMID- 27873901
TI  - Dielectric Constant Modelling with Soil-Air Composition and Its Effect on Sar
      Radar Signal Backscattered over Soil Surface.
AB  - The objective of this paper is to present the contribution of a new dielectric
      constant characterisation for the modelling of radar backscattering behaviour.
      Our analysis is based on a large number of radar measurements acquired during
      different experimental campaigns (Orgeval'94, Pays de Caux'98, 99). We propose a
      dielectric constant model, based on the combination of contributions from both
      soil and air fractions. This modelling clearly reveals the joint influence of the
      air and soil phases, in backscattering measurements over rough surfaces with
      large clods. A relationship is established between the soil fraction and soil
      roughness, using the Integral Equation Model (IEM), fitted to real radar data.
      Finally, the influence of the air fraction on the linear relationship between
      moisture and the backscattered radar signal is discussed.

PMID- 27873900
TI  - An Electrochemical DNA Biosensor Developed on a Nanocomposite Platform of Gold
      and Poly(propyleneimine) Dendrimer.
AB  - An electrochemical DNA nanobiosensor was prepared by immobilization of a 20mer
      thiolated probe DNA on electro-deposited generation 4 (G4) poly(propyleneimine)
      dendrimer (PPI) doped with gold nanoparticles (AuNP) as platform, on a glassy
      carbon electrode (GCE). Field emission scanning electron microscopy results
      confirmed the codeposition of PPI (which was linked to the carbon electrode
      surface by C-N covalent bonds) and AuNP ca 60 nm. Voltammetric interrogations
      showed that the platform (GCE/PPI-AuNP) was conducting and exhibited reversible
      electrochemistry (E degrees ' = 235 mV) in pH 7.2 phosphate buffer saline
      solution (PBS) due to the PPI component. The redox chemistry of PPI was pH
      dependent and involves a two electron, one proton process, as interpreted from a
      28 mV/pH value obtained from pH studies. The charge transfer resistance (Rct)
      from the electrochemical impedance spectroscopy (EIS) profiles of GCE/PPI-AuNP
      monitored with ferro/ferricyanide (Fe(CN)63-/4-) redox probe, decreased by 81%
      compared to bare GCE. The conductivity (in PBS) and reduced Rct (in Fe(CN)63-/4-)
      values confirmed PPI-AuNP as a suitable electron transfer mediator platform for
      voltammetric and impedimetric DNA biosensor. The DNA probe was effectively wired
      onto the GCE/PPI-AuNP via Au-S linkage and electrostatic interactions. The
      nanobiosensor responses to target DNA which gave a dynamic linear range of 0.01 -
      5 nM in PBS was based on the changes in Rct values using Fe(CN)63-/4- redox
      probe.

PMID- 27873902
TI  - An All Fiber White Light Interferometric Absolute Temperature Measurement System.
AB  - Recently the author of this article proposed a new signal processing algorithm
      for an all fiber white light interferometer. In this article, an all fiber white
      light interferometric absolute temperature measurement system is presented using
      the previously proposed signal processing algorithm. Stability and absolute
      temperature measurement were demonstrated. These two tests demonstrated the
      feasibility of absolute temperature measurement with an accuracy of 0.015 fringe
      and 0.0005 fringe, respectively. A hysteresis test from 373K to 873K was also
      presented. Finally, robustness of the sensor system towards laser diode
      temperature drift, AFMZI temperature drift and PZT non-linearity was
      demonstrated.

PMID- 27873903
TI  - Effect of External Vibration on PZT Impedance Signature.
AB  - Piezoelectric ceramic Lead Zirconate Titanate (PZT) transducers, working on the
      principle of electromechanical impedance (EMI), are increasingly applied for
      structural health monitoring (SHM) in aerospace, civil and mechanical
      engineering. The PZT transducers are usually surface bonded to or embedded in a
      structure and subjected to actuation so as to interrogate the structure at the
      desired frequency range. The interrogation results in the electromechanical
      admittance (inverse of EMI) signatures which can be used to estimate the
      structural health or integrity according to the changes of the signatures. In the
      existing EMI method, the monitored structure is only excited by the PZT
      transducers for the interrogating of EMI signature, while the vibration of the
      structure caused by the external excitations other than the PZT actuation is not
      considered. However, many structures work under vibrations in practice. To
      monitor such structures, issues related to the effects of vibration on the EMI
      signature need to be addressed because these effects may lead to
      misinterpretation of the structural health. This paper develops an EMI model for
      beam structures, which takes into account the effect of beam vibration caused by
      the external excitations. An experimental study is carried out to verify the
      theoretical model. A lab size specimen with different external excitations is
      tested and the effect of vibration on EMI signature is discussed.

PMID- 27873904
TI  - Microsensors for in vivo Measurement of Glutamate in Brain Tissue.
AB  - Several immobilized enzyme-based electrochemical biosensors for glutamate
      detection have been developed over the last decade. In this review, we compare
      first and second generation sensors. Structures, working mechanisms, interference
      prevention, in vitro detection characteristics and in vivo performance are
      summarized here for those sensors that have successfully detected brain glutamate
      in vivo. In brief, first generation sensors have a simpler structure and are
      faster in glutamate detection. They also show a better sensitivity to glutamate
      during calibration in vitro. For second generation sensors, besides their less
      precise detection, their fabrication is difficult to reproduce, even with a semi
      automatic dip-coater. Both generations of sensors can detect glutamate levels in
      vivo, but the reported basal levels are different. In general, second generation
      sensors detect higher basal levels of glutamate compared with the results
      obtained from first generation sensors. However, whether the detected glutamate
      is indeed from synaptic sources is an issue that needs further attention.

PMID- 27873906
TI  - Determination of Dopamine in the Presence of Ascorbic Acid by Nafion and Single
      Walled Carbon Nanotube Film Modified on Carbon Fiber Microelectrode.
AB  - Carbon fiber microelectrode (CFME) modified by Nafion and single-walled carbon
      nanotubes (SWNTs) was studied by voltammetric methods in phosphate buffer saline
      (PBS) solution at pH 7.4. The Nafion-SWNTs/CFME modified microelectrode exhibited
      strongly enhanced voltammetric sensitivity and selectivity towards dopamine (DA)
      determination in the presence of ascorbic acid (AA). Nafion-SWNTs film
      accelerated the electron transfer reaction of DA, but Nafion film as a negatively
      charged polymer restrained the electrochemical response of AA. Voltammetric
      techniques separated the anodic peaks of DA and AA, and the interference from AA
      was effectively excluded from DA determination. Linear calibration plots were
      obtained in the DA concentration range of 10 nM - 10 MUM and the detection limit
      of the anodic current was determined to be 5 nM at a signal-to-noise ratio of 3.
      The study results demonstrate that DA can be determined without any interference
      from AA at the modified microelectrode, thereby increasing the sensitivity,
      selectivity, and reproducibility and stability.

PMID- 27873905
TI  - A Solid Trap and Thermal Desorption System with Application to a Medical
      Electronic Nose.
AB  - In this paper, a solid trap/thermal desorption-based odorant gas condensation
      system has been designed and implemented for measuring low concentration odorant
      gas. The technique was successfully applied to a medical electronic nose system.
      The developed system consists of a flow control unit, a temperature control unit
      and a sorbent tube. The theoretical analysis and experimental results indicate
      that gas condensation, together with the medical electronic nose system can
      significantly reduce the detection limit of the nose system and increase the
      system's ability to distinguish low concentration gas samples. In addition, the
      integrated system can remove the influence of background components and
      fluctuation of operational environment. Even with strong disturbances such as
      water vapour and ethanol gas, the developed system can classify the test samples
      accurately.

PMID- 27873907
TI  - Bioavailability of Cd, Zn and Hg in Soil to Nine Recombinant Luminescent Metal
      Sensor Bacteria.
AB  - A set of nine recombinant heavy metal-specific luminescent bacterial sensors
      belonging to Gram-negative (Escherichia and Pseudomonas) and Gram-positive
      (Staphylococcus and Bacillus) genera and containing various types of recombinant
      metalresponse genetic elements was characterized for heavy metal bioavailability
      studies. All nine strains were induced by Hg and Cd and five strains also by Zn.
      As a lowest limit, the sensors were detecting 0.03 MUg.L-1 of Hg, 2 MUg.L-1 of Cd
      and 400 MUg.L-1 of Zn. Limit of determination of the sensors depended mostly on
      metal-response element, whereas the toxicity of those metals towards the sensor
      bacteria was mostly dependent on the type of the host bacterium, with Gram
      positive strains being more sensitive than Gram-negative ones. The set of sensors
      was used to evaluate bioavailability of Hg, Cd and Zn in spiked soils. The
      bioavailable fraction of Cd and Zn in soil suspension assay (2.6 - 5.1% and 0.32 
      0.61%, of the total Cd and Zn, respectively) was almost comparable for all the
      sensors, whereas the bioavailability of Hg was about 10-fold higher for Gram
      negative sensor cells (30.5% of total Hg), compared to Gram-positive ones (3.2%
      of the total Hg). For Zn, the bioavailable fraction in soil-water suspensions and
      respective extracts was comparable (0.37 versus 0.33% of the total Zn). However,
      in the case of Cd, for all the sensors used and for Hg concerning only Gram
      negative sensor strains, the bioavailable fraction in soilwater suspensions
      exceeded the water-extracted fraction about 14-fold, indicating that upon direct
      contact, an additional fraction of Cd and Hg was mobilized by those sensor
      bacteria. Thus, for robust bioavailability studies of heavy metals in soils any
      type of genetic metal-response elements could be used for the construction of the
      sensor strains. However, Gram-positive and Gram-negative senor strains should be
      used in parallel as the bioavailability of heavy metals to those bacterial groups
      may be different.

PMID- 27873909
TI  - A Novel Vehicle Classification Using Embedded Strain Gauge Sensors.
AB  - This paper presents a new vehicle classification and develops a traffic
      monitoring detector to provide reliable vehicle classification to aid traffic
      management systems. The basic principle of this approach is based on measuring
      the dynamic strain caused by vehicles across pavement to obtain the corresponding
      vehicle parameters - wheelbase and number of axles - to then accurately classify
      the vehicle. A system prototype with five embedded strain sensors was developed
      to validate the accuracy and effectiveness of the classification method.
      According to the special arrangement of the sensors and the different time a
      vehicle arrived at the sensors one can estimate the vehicle's speed accurately,
      corresponding to the estimated vehicle wheelbase and number of axles. Because of
      measurement errors and vehicle characteristics, there is a lot of overlap between
      vehicle wheelbase patterns. Therefore, directly setting up a fixed threshold for
      vehicle classification often leads to low-accuracy results. Using the machine
      learning pattern recognition method to deal with this problem is believed as one
      of the most effective tools. In this study, support vector machines (SVMs) were
      used to integrate the classification features extracted from the strain sensors
      to automatically classify vehicles into five types, ranging from small vehicles
      to combination trucks, along the lines of the Federal Highway Administration
      vehicle classification guide. Test bench and field experiments will be introduced
      in this paper. Two support vector machines classification algorithms (one-against
      all, one-against-one) are used to classify single sensor data and multiple sensor
      combination data. Comparison of the two classification method results shows that
      the classification accuracy is very close using single data or multiple data. Our
      results indicate that using multiclass SVM-based fusion multiple sensor data
      significantly improves the results of a single sensor data, which is trained on
      the whole multisensor data set.

PMID- 27873910
TI  - Usage of Underground Space for 3D Cadastre Purposes and Related Problems in
      Turkey.
AB  - Modern cities have been trying to meet their needs for space by using not only
      surface structures but also by considering subsurface space use. It is also
      anticipated that without planning of underground spaces for supporting surface
      city life in the years and generations to come, there will be serious and
      unavoidable problems with growing populations. The current Turkish cadastral
      system, including land right registrations, has been trying to meet users' needs
      in all aspects since 1924. Today Turkey's national cadastre services are carried
      out by the General Directorate of Land Titles and Cadastre (TKGM). The Cadastre
      Law, Number 3402, was approved in 1985 to eliminate problems by gathering all
      existing cadastral regulations under one law and also to produce 3D cadastral
      bases to include underground spaces and determine their legal status in Turkey.
      Although the mandate for 3D cadastre works is described and explained by the
      laws, until now the bases have been created in 2D and the reality is that legal
      gaps and deficiencies presently exist in them. In this study, the usage of
      underground spaces for the current cadastral system in Turkey was briefly
      evaluated, the concept of 3D cadastral data is examined and the need for using
      subsurface and 3D cadastre in addition to the traditional 2D register system,
      related problems and registration are mentioned with specific examples, but
      without focusing on a specific model.

PMID- 27873908
TI  - Selective D3 Receptor Antagonist SB-277011-A Potentiates the Effect of Cocaine on
      Extracellular Dopamine in the Nucleus Accumbens: a Dual Core-Shell Voltammetry
      Study in Anesthetized Rats.
AB  - Dopamine (DA) D3 receptors have been associated with drug intake and abuse and
      selectively distribute in the brain circuits responding to drug administration.
      Here we examined the effects of an acute systemic administration of cocaine (15
      mg/kg) alone or preceded by treatment with the selective D3 receptor antagonist
      SB-277011-A (10 mg/kg) on DA levels concurrently in the rat nucleus accumbens
      shell and core sub-regions (NAcshell and NAccore, respectively). It is shown that
      cocaine increases extracellular DA in both compartments and that blocking D3
      receptors with SB-277011-A, although the latter is devoid of dopaminergic effects
      per se, potentiates these effects. No differences in the amplitude of the
      response were observed between NAcshell and NAccore compartments, though the
      dopaminergic response in the NAcshell was transient whereas that in the NAccore
      rose slowly to reach a plateau. These results demonstrate the feasibility to use
      multiprobe voltammetry to measure discrete monoaminergic responses in discrete
      areas of the brain and confirm the effect of D3 receptors antagonist at modifying
      the neurochemical effects of cocaine.

PMID- 27873911
TI  - Classification Metrics for Improved Atmospheric Correction of Multispectral VNIR
      Imagery.
AB  - Multispectral visible/near-infrared (VNIR) earth observation satellites, e.g.,
      Ikonos, Quickbird, ALOS AVNIR-2, and DMC, usually acquire imagery in a few (3 -
      5) spectral bands. Atmospheric correction is a challenging task for these images
      because the standard methods require at least one shortwave infrared band (around
      1.6 or 2.2 um) or hyperspectral instruments to derive the aerosol optical
      thickness. New classification metrics for defining cloud, cloud over water, haze,
      water, and saturation are presented to achieve improvements for an automatic
      processing system. The background is an ESA contract for the development of a
      prototype atmospheric processor for the optical payload AVNIR-2 on the ALOS
      platform.

PMID- 27873912
TI  - Quantifying Cutting and Wearing Behaviors of TiN- and CrNCoated AISI 1070 Steel.
AB  - Hard coatings such as titanium nitride (TiN) and chromium nitride (CrN) are
      widely used in cutting and forming tools against wear and corrosion. In the
      present study, hard coating films were deposited onto AISI 1070 steels by a
      cathodic arc evaporation plating (CAVP) technique. These samples were subjected
      to wear in a conventional lathe for investigating the tribological behaviour of
      coating structure, and prenitrided subsurface composition was characterized using
      scanning electron microscopy (SEM), line scan analyses and X-ray diffraction
      (XRD). The wear properties of TiN- and CrNcoated samples were determined using an
      on-line monitoring system. The results show that TiN-coated samples demonstrate
      higher wear resistance than CrN-coated samples.

PMID- 27873913
TI  - Mesoscale Near-Surface Wind Speed Variability Mapping with Synthetic Aperture
      Radar.
AB  - Operationally-significant wind speed variability is often observed within
      synthetic aperture radar-derived wind speed (SDWS) images of the sea surface.
      This paper is meant as a first step towards automated distinguishing of
      meteorological phenomena responsible for such variability. In doing so, the
      research presented in this paper tests feature extraction and pixel aggregation
      techniques focused on mesoscale variability of SDWS. A sample of twenty eight
      SDWS images possessing varying degrees of near-surface wind speed variability
      were selected to serve as case studies. Gaussian high- and low-pass, local
      entropy, and local standard deviation filters performed well for the feature
      extraction portion of the research while principle component analysis of the
      filtered data performed well for the pixel aggregation. The findings suggest
      recommendations for future research.

PMID- 27873914
TI  - Remote Sensing Monitoring of Changes in Soil Salinity: A Case Study in Inner
      Mongolia, China.
AB  - This study used archived remote sensing images to depict the history of changes
      in soil salinity in the Hetao Irrigation District in Inner Mongolia, China, with
      the purpose of linking these changes with land and water management practices and
      to draw lessons for salinity control. Most data came from LANDSAT satellite
      images taken in 1973, 1977, 1988, 1991, 1996, 2001, and 2006. In these years salt
      affected areas were detected using a normal supervised classification method.
      Corresponding cropped areas were detected from NVDI (Normalized Difference
      Vegetation Index) values using an unsupervised method. Field samples and
      agricultural statistics were used to estimate the accuracy of the classification.
      Historical data concerning irrigation/drainage and the groundwater table were
      used to analyze the relation between changes in soil salinity and land and water
      management practices. Results showed that: (1) the overall accuracy of remote
      sensing in detecting soil salinity was 90.2%, and in detecting cropped area, 98%;
      (2) the installation/innovation of the drainage system did help to control
      salinity; and (3) a low ratio of cropped land helped control salinity in the
      Hetao Irrigation District. These findings suggest that remote sensing is a useful
      tool to detect soil salinity and has potential in evaluating and improving land
      and water management practices.

PMID- 27873916
TI  - Electrochemical Performance of a Carbon Nanotube/La-Doped TiO2 Nanocomposite and
      its Use for Preparation of an Electrochemical Nicotinic Acid Sensor.
AB  - A carbon nanotube/La-doped TiO2 (La-TiO2) nanocomposite (CLTN) was prepared by a
      procedure similar to a complex/adsorption process. Scanning electron microscopy
      (SEM) images show that the La-TiO2 distributes on the carbon nanotube walls. The
      CLTN was mixed with paraffin to form a CLTN paste for the CLTN paste electrode
      (CLTNPE). The electrochemical characteristics of CLTNPE were compared with that
      of conventional carbon electrodes such as the carbon paste electrode (CPE) and
      glass carbon electrode (GC). The CLTNPE exhibits electrochemical activity and was
      used to investigate the electrochemistry of nicotinic acid (NA). The modified
      electrode has a strong electrocatalytic effect on the redox of NA. The cyclic
      voltammetry (CV) redox potential of NA at the CLTNPE is 320 mV. The oxidation
      process of NA on the CLTNPE is pH dependent. A sensitive chronoamperometric
      response for NA was obtained covering a linear range from 1.0*10-6 mol.L-1 to
      1.2*10-4 mol.L-1, with a detection limit of 2.7*10-7 mol.L-1. The NA sensor
      displays a remarkable sensitivity and stability. The mean recovery of NA in the
      human urine is 101.8%, with a mean variation coefficient (RSD) of 2.6%.

PMID- 27873915
TI  - Recent Progress in Nucleic Acid Aptamer-Based Biosensors and Bioassays.
AB  - As the key constituents of the genetic code, the importance of nucleic acids to
      life has long been appreciated. Despite being composed of only four structurally
      similar nucleotides, single-stranded nucleic acids, as in single-stranded DNAs
      and RNAs, can fold into distinct three-dimensional shapes due to specific
      intramolecular interactions and carry out functions beyond serving as templates
      for protein synthesis. These functional nucleic acids (FNAs) can catalyze
      chemical reactions, regulate gene expression, and recognize target molecules.
      Aptamers, whose name is derived from the Latin word aptus meaning "to fit", are
      oligonucleotides that can bind their target ligands with high affinity and
      specificity. Since aptamers exist in nature but can also be artificially isolated
      from pools of random nucleic acids through a process called in vitro selection,
      they can potentially bind a diverse array of compounds. In this review, we will
      discuss the research that is being done to develop aptamers against various
      biomolecules, the progress in engineering biosensors by coupling aptamers to
      signal transducers, and the prospect of employing these sensors for a range of
      chemical and biological applications. Advances in aptamer technology emphasizes
      that nucleic acids are not only the fundamental molecules of life, they can also
      serve as research tools to enhance our understanding of life. The possibility of
      using aptamer-based tools in drug discovery and the identification of infectious
      agents can ultimately augment our quality of life.

PMID- 27873917
TI  - Determination of Vitamin C (Ascorbic Acid) Using High Performance Liquid
      Chromatography Coupled with Electrochemical Detection.
AB  - Vitamin C (ascorbic acid, ascorbate, AA) is a water soluble organic compound that
      participates in many biological processes. The main aim of this paper was to
      utilize two electrochemical detectors (amperometric - Coulouchem III and
      coulometric - CoulArray) coupled with flow injection analysis for the detection
      of ascorbic acid. Primarily, we optimized the experimental conditions. The
      optimized conditions were as follows: detector potential 100 mV, temperature 25 
      degrees C, mobile phase 0.09% TFA:ACN, 3:97 (v/v) and flow rate 0.13 mL.min-1.
      The tangents of the calibration curves were 0.3788 for the coulometric method and
      0.0136 for the amperometric one. The tangent of the calibration curve measured by
      the coulometric detector was almost 30 times higher than the tangent measured by
      the amperometric detector. Consequently, we coupled a CoulArray electrochemical
      detector with high performance liquid chromatography and estimated the detection
      limit for AA as 90 nM (450 fmol per 5 MUL injection). The method was used for the
      determination of vitamin C in a pharmaceutical preparations (98 +/- 2 mg per
      tablet), in oranges (Citrus aurantium) (varied from 30 to 56 mg/100 g fresh
      weight), in apples (Malus sp.) (varied from 11 to 19 mg/100 g fresh weight), and
      in human blood serum (varied from 38 to 78 MUM). The recoveries were also
      determined.

PMID- 27873918
TI  - Integrated Optic Surface Plasmon Resonance Measurements in a Borosilicate Glass
      Substrate.
AB  - The surface plasmon resonance (SPR) technique is a well-known optical method that
      can be used to measure the refractive index of organic nano-layers adsorbed on a
      thin metal film. Although there are many configurations for measuring
      biomolecular interactions, SPR-based techniques play a central role in many
      current biosensing experiments, since they are the most suited for sensitive and
      quantitative kinetic measurements. Here we give some results from the analysis
      and numerical elaboration of SPR data from integrated optics experiments in a
      particular borosilicate glass, chosen for its composition offering the rather low
      refractive index of 1.4701 at 633 nm wavelength. These data regard the flow over
      the sensing region (metal window) of different solutions with refractive indexes
      in the range of interest (1.3/1.5) for the detection of contaminants in aqueous
      solutions. After a discussion of the principles of SPR, of the metal window
      design optimization by means of optical interaction numerical modeling, and of
      waveguide fabrication techniques, we give a description of system setup and
      experimental results. Optimum gold film window thickness and width in this guided
      wave configuration has been for the first time derived and implemented on an
      integrated optic prototype device. Its characterization is given by means of the
      real time waveguide output intensity measurements, which correspond to the
      interaction between the sensing gold thin film window and the flowing analyte.
      The SPR curve was subsequently inferred. Finally, a modified version of the
      device is reported, with channel waveguides arranged in a Y-junction optical
      circuit, so that laser source stability requirements are lowered by a factor of
      85 dB, making possible the use of low cost sources in practical applications.

PMID- 27873919
TI  - NO2 Detection Using Microcantilever Based Potentiometry.
AB  - A highly sensitive and novel sensor platform for gases and volatile chemicals
      using microcantilever based potentiometry is reported. A resonant cantilever is
      used to detect the changes in surface work functions of functionalized substrates
      caused by adsorption of target gas molecules. Surface work function (SWF) changes
      were measured for different functionalization layers made of transition metal
      oxide thin films with the flow of NO2. The rate of change in SWF for In2O3 and
      SnO2 were found to be ~80 and ~100 MUV/sec, respectively, for 70 ppm NO2. A
      sensitivity of 64 MUV/sec for SWF change was also found for 70 ppm NO2
      concentration for isolated clusters of ZnO nanowires, indicating that this
      technique is applicable even for nano-clusters of sensing materials where
      amperometric detection is impossible due to material discontinuity. NO2 detection
      as low as 400 ppb was possible using highly insulating In2O3 and SnO2 thin films
      (resistivity > 1 TOmega/?). Two different forms of nano scale graphite were
      compared with the transition oxide based functionalization layer for sensing sub
      ppm NO2 sensing. It was observed that nanostructured graphite (NG) shows much
      higher sensitivity and lower response time than transition metal oxides.

PMID- 27873920
TI  - Mercury Determination in Fish Samples by Chronopotentiometric Stripping Analysis
      Using Gold Electrodes Prepared from Recordable CDs.
AB  - A simple method for manufacturing gold working electrodes for
      chronopotentiometric stripping measurements from recordable CD-R's is described.
      These gold electrodes are much cheaper than commercially available ones. The
      electrochemical behavior of such an electrode and the working parameters for
      mercury determination by chronopotentiometric stripping analysis were studied.
      Detection limit was 0.30 MUg Hg/L and determination limit was 1.0 MUg Hg/L for a
      deposition time of 600 s. Using the developed working electrodes it was possible
      to determine the total mercury in fish samples. A method for fish sample
      digestion was developed by using a mixture of fuming nitric acid and both
      concentrated sulfuric and hydrochloric acids. The recovery degree for a known
      amount of mercury introduced in the sample before digestion was 95.3% (n=4).

PMID- 27873921
TI  - Rapid Urban Mapping Using SAR/Optical Imagery Synergy.
AB  - This paper highlights the potential of combining Synthetic Aperture Radar (SAR)
      and optical data for operational rapid urban mapping. An algorithm consisting of
      a completely unsupervised procedure for processing pairs of co-registered
      SAR/optical images is proposed. In a first stage, a texture analysis is conducted
      independently on the two images using eight different chain-based Gaussian
      models. In a second stage, the resulting texture images are partitioned by an
      unsupervised fuzzy K-means approach. Finally, a fuzzy decision rule is used to
      aggregate the results provided by the classification of texture images obtained
      from the pair of SAR and optical images. The method was tested and validated on
      images of Bucharest (Romania) and Cayenne (French Guiana). These two study areas
      are of different terrain relief, urban settlement structure and land cover
      complexity. The data set included Radarsat-1/ENVISAT and SPOT-4/5 images. The
      developed SAR/optical information fusion scheme improved the capabilities of
      urban areas extraction when compared with the separate use of SAR and optical
      sensors. It also proved to be suitable for monitoring urbanization development.
      The encouraging results thus confirm the potential of combining information from
      SAR and optical sensors for timely urban area analysis, as required in cases of
      disaster management and planning in urban sprawl areas.

PMID- 27873922
TI  - Interferometric Phase Improvement Based on Polarimetric Data Fusion.
AB  - In this paper, a method is proposed to improve the interferometric phase quality,
      based on fusing data from different polarimetric channels. Since lower amplitude
      implies less reliable phase in general, the phase quality of polarimetric
      interferometric data can be improved by seeking optimal fusion of data from
      different polarizations to maximize the resulting amplitude. In the proposed
      approach, for each pixel, two coherent polarimetric scattering vectors are
      synchronously projected onto a same optimum direction, maximizing the lower
      amplitude of the two projections. In the single-look case, the fused phase is
      equivalent to the weighted average of phases in all polarimetric channels. It
      provides a good physical explanation of the proposed approach. Without any
      filtering, the phase noise and the number of residue points are significantly
      reduced, and the interferometric phase quality is greatly improved. It is a
      useful tool to preprocess the phase ahead of phase unwrapping. The Cloude's
      coherence optimization method is used for a comparison. Using the data collected
      by SIR-C/X-SAR, the authors demonstrate the effectiveness and the robustness of
      the proposed approach.

PMID- 27873923
TI  - Recent Updates of DNA Incorporated in Carbon Nanotubes and Nanoparticles for
      Electrochemical Sensors and Biosensors.
AB  - Innovations in the field of electrochemical sensors and biosensors are of much
      importance nowadays. These devices are designed with probes and micro electrodes.
      The miniaturized designs of these sensors allow analyses of materials without
      damaging the samples. Some of these sensors are also useful for real time
      analysis within the host system, so these sensors are considered to be more
      advantageous than other types of sensors. The active sensing materials used in
      these types of sensors can be any material that acts as a catalyst for the
      oxidation or reduction of particular analyte or set of analytes. Among various
      kinds of sensing materials, deoxyribonucleic acid (DNA), carbon nanotubes (CNTs)
      and nanoparticles have received considerable attraction in recent years. DNA is
      one of the classes of natural polymers, which can interact with CNTs and
      nanoparticles to form new types of composite materials. These composite materials
      have also been used as sensing materials for sensor applications. They have
      advantages in characteristics such as extraordinary low weight and
      multifunctional properties. In this article, advantages of DNA incorporated in
      CNT and nanoparticle hybrids for electrochemical sensors and biosensors are
      presented in detail, along with some key results noted from the literature.

PMID- 27873924
TI  - Analysis of Land Use Change and Urbanization in the Kucukcekmece Water Basin
      (Istanbul, Turkey) with Temporal Satellite Data using Remote Sensing and GIS.
AB  - Accurate and timely information about land use and land cover (LULC) and its
      changes in urban areas are crucial for urban land management decision-making,
      ecosystem monitoring and urban planning. Also, monitoring and representation of
      urban sprawl and its effects on the LULC patterns and hydrological processes of
      an urbanized watershed is an essential part of water resource planning and
      management. This paper presents an image analysis study using multi temporal
      digital satellite imagery of LULC and changes in the Kucukcekmece Watershed
      (Metropolitan Istanbul, Turkey) from 1992 to 2006. The Kucukcekmece Basin
      includes portions of the Kucukcekmece District within the municipality of
      Istanbul so it faces a dramatic urbanization. An urban monitoring analysis
      approach was first used to implement a land cover classification. A change
      detection method controlled with ground truth information was then used to
      determine changes in land cover. During the study period, the variability and
      magnitude of hydrological components based on land-use patterns were cumulatively
      influenced by urban sprawl in the watershed. The proposed approach, which uses a
      combination of Remote Sensing (RS) and Geographical Information System (GIS)
      techniques, is an effective tool that enhances land-use monitoring, planning, and
      management of urbanized watersheds.

PMID- 27873925
TI  - Multifunctional Polypeptide EQCN Sensors: Probing the Cysteamine-Glutathione Film
      Permeability with Hg(II) Ions.
AB  - Multifunctional films are the basis of biosensors and play an important role in
      the emerging field of nanobioelectronics. In this work, films of a tripeptide
      glutathione (GSH) immobilized on a self-assembled monolayer of cysteamine (CA
      SAM) on a quartz crystal Au piezosensor have been synthesized and characterized
      using electrochemical quartz crystal nanogravimetry (EQCN) with a Hg(II) ion
      probe. It has been found that in contrast to previously studied Au/GSH films, the
      Au/CA-GSH films strongly hinder the formation of Hg0 with bulk properties while
      still allowing for relatively easy permeation by Hg(II) ions. This results in
      complete disappearance of the sharp Hg0 electrodissolution peak which is observed
      on bare Au and Au/GSH piezosensors. The multiple-peak anodic behavior of Au/CA
      and bare Au is replaced by a single high-field anodic peak of mercury reoxidation
      in the case of Au/CA-GSH sensors. The mass-to-charge plots indicate predominant
      ingress/egress of Hg(II) to/from the film. The strong hindrance of CA-SAM to bulk
      Hg0 formation is attributed to film-stabilizing formation of surface (CA)2Hg2+
      complexes with conformation evaluated by ab initio quantum mechanical
      calculations of electronic structure using Hartree-Fock methods. The associates
      CA-GSH provide an additional functionality of the side sulfhydryl group which is
      free for interactions, e.g. with heavy metals. It is proposed that in the film,
      the CA-GSH molecules can assume open (extended) conformation or bent hydrogen
      bonded conformation with up to four possible internal hydrogen bonds.

PMID- 27873926
TI  - Microwave Imaging of Cotton Bales.
AB  - Modern moisture restoration systems are increasingly capable of adding water to
      cotton bales. However, research has identified large variations in internal
      moisture within bales that are not readily monitored by current systems. While
      microwave moisture sensing systems can measure average bale moisture, this can be
      deceptive where water is unevenly distributed. In some cases, localized internal
      moisture levels exceed 7.5%, the upper safe limit for cotton bale storage, as
      determined by the USDA, as above this level, bales degrade and lose value. A high
      proportion of stored bales containing excess moisture have been discovered
      throughout the US in increasing numbers over the past several seasons, making the
      detection and prevention of this occurrence a critical goal. Previous research by
      the authors resulted in the development of microwave moisture-sensing technology.
      The current study examines an extension to this technology to allow for detailed
      cotton bale moisture imaging. The new technique incorporates a narrow beam
      imaging antenna coupled to a tomographic imaging algorithm. The imaging technique
      was able to resolve small (< 1 cm) high-permittivity structures against a low
      permittivity background. Moreover, the system was able to identify structures of
      known permittivity with high accuracy (coefficient of determination (r2) > 0.99).
      In preliminary testing on a wet commercial UD bale, the technique was able to
      accurately image and resolve the location of the pre-placed internal wet layer.

PMID- 27873927
TI  - A Mobile Sensor Network System for Monitoring of Unfriendly Environments.
AB  - Observing microclimate changes is one of the most popular applications of
      wireless sensor networks. However, some target environments are often too
      dangerous or inaccessible to humans or large robots and there are many challenges
      for deploying and maintaining wireless sensor networks in those unfriendly
      environments. This paper presents a mobile sensor network system for solving this
      problem. The system architecture, the mobile node design, the basic behaviors and
      advanced network capabilities have been investigated respectively. A wheel-based
      robotic node architecture is proposed here that can add controlled mobility to
      wireless sensor networks. A testbed including some prototype nodes has also been
      created for validating the basic functions of the proposed mobile sensor network
      system. Motion performance tests have been done to get the positioning errors and
      power consumption model of the mobile nodes. Results of the autonomous deployment
      experiment show that the mobile nodes can be distributed evenly into the
      previously unknown environments. It provides powerful support for network
      deployment and maintenance and can ensure that the sensor network will work
      properly in unfriendly environments.

PMID- 27873928
TI  - Use of Reflectance Measurements for the Detection of N, P, K, ADF and NDF
      Contents in Sainfoin Pasture.
AB  - The objective of this study was to determine the relationships between nitrogen
      (N), phosphorus (P), potassium (P), acid detergent fiber (ADF) and neutral
      detergent fiber (NDF) contents of sainfoin (Onobrychis sativa Lam.) pasture and
      canopy reflectance. Canopy reflectance measurements were made by using a portable
      spectroradiometer. An experiment was conducted in the Turkey in May and June in
      2007 and 2008. Sainfoin pasture N, P, K, ADF and NDF contents correlated linearly
      with the reflectance ratios R780/650 (0.61<= r2 <=0.80) and first derivatives of
      the reflectance ratios 760/630 (0.70<= r2 <=0.84). Linear equations between each
      forage variable and reflectance or first derivatives reflectance had high r2
      (0.68<= r2 <=0.83 and 0.79<= r2 <=0.90, respectively) in R780 and R760
      wavelengths. In stepwise regression of the reflectance (in 460, 550, 650 and 780
      nm wavelengths), the r2 of predicted and measured N, P, K, ADF and NDF contents
      of sainfoin pasture were (0.85, 0.85, 0.78, 0.81 and 0.74, respectively), in
      stepwise regression of the first derivatives of reflectance (in 440, 530, 630 and
      760 nm wavelengths), the r2 of predicted and measured N, P, K, ADF and NDF
      contents of sainfoin pasture were (0.87, 0.91, 0.83, 0.93 and 0.86,
      respectively). Our results suggest that canopy reflectance in blue, green, red
      and near infrared wavebands with NIR/Red and NDVI ratios can be used for
      nondestructive prediction of forage quality variables in sainfoin pasture.

PMID- 27873929
TI  - Minimal-Drift Heading Measurement using a MEMS Gyro for Indoor Mobile Robots.
AB  - To meet the challenges of making low-cost MEMS yaw rate gyros for the precise
      self-localization of indoor mobile robots, this paper examines a practical and
      effective method of minimizing drift on the heading angle that relies solely on
      integration of rate signals from a gyro. The main idea of the proposed approach
      is consists of two parts; 1) self-identification of calibration coefficients that
      affects long-term performance, and 2) threshold filter to reject the broadband
      noise component that affects short-term performance. Experimental results with
      the proposed phased method applied to Epson XV3500 gyro demonstrate that it
      effectively yields minimal drift heading angle measurements getting over major
      error sources in the MEMS gyro output.

PMID- 27873930
TI  - Can Commercial Digital Cameras Be Used as Multispectral Sensors? A Crop
      Monitoring Test.
AB  - The use of consumer digital cameras or webcams to characterize and monitor
      different features has become prevalent in various domains, especially in
      environmental applications. Despite some promising results, such digital camera
      systems generally suffer from signal aberrations due to the on-board image
      processing systems and thus offer limited quantitative data acquisition
      capability. The objective of this study was to test a series of radiometric
      corrections having the potential to reduce radiometric distortions linked to
      camera optics and environmental conditions, and to quantify the effects of these
      corrections on our ability to monitor crop variables. In 2007, we conducted a
      five-month experiment on sugarcane trial plots using original RGB and modified
      RGB (Red-Edge and NIR) cameras fitted onto a light aircraft. The camera settings
      were kept unchanged throughout the acquisition period and the images were
      recorded in JPEG and RAW formats. These images were corrected to eliminate the
      vignetting effect, and normalized between acquisition dates. Our results suggest
      that 1) the use of unprocessed image data did not improve the results of image
      analyses; 2) vignetting had a significant effect, especially for the modified
      camera, and 3) normalized vegetation indices calculated with vignetting-corrected
      images were sufficient to correct for scene illumination conditions. These
      results are discussed in the light of the experimental protocol and
      recommendations are made for the use of these versatile systems for quantitative
      remote sensing of terrestrial surfaces.

PMID- 27873931
TI  - A Comprehensive Automated 3D Approach for Building Extraction, Reconstruction,
      and Regularization from Airborne Laser Scanning Point Clouds.
AB  - Three dimensional city models are necessary for supporting numerous management
      applications. For the determination of city models for visualization purposes,
      several standardized workflows do exist. They are either based on photogrammetry
      or on LiDAR or on a combination of both data acquisition techniques. However, the
      automated determination of reliable and highly accurate city models is still a
      challenging task, requiring a workflow comprising several processing steps. The
      most relevant are building detection, building outline generation, building
      modeling, and finally, building quality analysis. Commercial software tools for
      building modeling require, generally, a high degree of human interaction and most
      automated approaches described in literature stress the steps of such a workflow
      individually. In this article, we propose a comprehensive approach for automated
      determination of 3D city models from airborne acquired point cloud data. It is
      based on the assumption that individual buildings can be modeled properly by a
      composition of a set of planar faces. Hence, it is based on a reliable 3D
      segmentation algorithm, detecting planar faces in a point cloud. This
      segmentation is of crucial importance for the outline detection and for the
      modeling approach. We describe the theoretical background, the segmentation
      algorithm, the outline detection, and the modeling approach, and we present and
      discuss several actual projects.

PMID- 27873932
TI  - Evaluation of Different Outlier Detection Methods for GPS Networks.
AB  - GPS (Global Positioning System) devices can be used in many applications which
      require accurate point positioning in geosciences. Accuracy of GPS decreases due
      to outliers resulted from the errors inherent in GPS observations. Several
      approaches have been developed to detect outliers in geodetic observations. It is
      important to determine which method is most effective at distinguishing outliers
      from normal observations. This paper investigates the behavior of conventional
      statistical test methods (Data Snooping (DS), Tau and t tests), some robust
      methods (Andrews's M-Estimation, Huber's MEstimation, Tukey's M-Estimation,
      Danish Method, Yang-I M-Estimation, Yang-II MEstimation, and fuzzy logic method
      in detection of outliers for three GPS networks having different characteristics.
      Test results are evaluated and the performances of different methods are
      presented quantitatively.

PMID- 27873933
TI  - Nano-Scale Characterization of a Piezoelectric Polymer (Polyvinylidene
      Difluoride, PVDF).
AB  - The polymer polyvinylidene difluoride (PVDF) has unique piezoelectric properties
      favorable for Micro-Electro-Mechanical Systems (MEMS) and Nano-Electro-Mechanical
      Systems (NEMS) applications. In the present research, we conducted nanometer
      length scale characterization of this material using several high-resolution
      techniques. Specifically, we used an atomic force microscope (AFM) to study the
      nanoand microstructures of the PVDF under stress and to measure their nanoscale
      conductivity and piezoelectricity. We found that the surface morphology,
      electronic structure, and microstructure are profoundly affected under electrical
      potential. Such a behavior is important for the properties and performance of
      MEMS and NEMS.

PMID- 27873934
TI  - Selectivity Enhancement in Multisensor Systems Using Flow Modulation Techniques.
AB  - In this paper, the use of a new technique to obtain transient sensor information
      is introduced and its usefulness to improve the selectivity of metal oxide gas
      sensors is discussed. The method is based on modulating the flow of the carrier
      gas that brings the species to be measured into the sensor chamber. In such a
      way, the analytes' concentration at the surface of the sensors is altered. As a
      result, reproducible patterns in the sensor response develop, which carry
      important information for helping the sensor system, not only to discriminate
      among the volatiles considered but also to semi-quantify them. This has been
      proved by extracting features from sensor dynamics using the discrete wavelet
      transform (DWT) and by building and validating support vector machine (SVM)
      classification models. The good results obtained (100% correct identification
      among 5 volatile compounds and nearly a 89% correct simultaneous identification
      and quantification of these volatiles), which clearly outperform those obtained
      when the steady-state response is used, prove the concept behind flow modulation.

PMID- 27873936
TI  - Improved Progressive Polynomial Algorithm for Self-Adjustment and Optimal
      Response in Intelligent Sensors.
AB  - The development of intelligent sensors involves the design of reconfigurable
      systems capable of working with different input sensors signals. Reconfigurable
      systems should expend the least possible amount of time readjusting. A self
      adjustment algorithm for intelligent sensors should be able to fix major problems
      such as offset, variation of gain and lack of linearity with good accuracy. This
      paper shows the performance of a progressive polynomial algorithm utilizing
      different grades of relative nonlinearity of an output sensor signal. It also
      presents an improvement to this algorithm which obtains an optimal response with
      minimum nonlinearity error, based on the number and selection sequence of the
      readjust points. In order to verify the potential of this proposed criterion, a
      temperature measurement system was designed. The system is based on a thermistor
      which presents one of the worst nonlinearity behaviors. The application of the
      proposed improved method in this system showed that an adequate sequence of the
      adjustment points yields to the minimum nonlinearity error. In realistic
      applications, by knowing the grade of relative nonlinearity of a sensor, the
      number of readjustment points can be determined using the proposed method in
      order to obtain the desired nonlinearity error. This will impact on readjustment
      methodologies and their associated factors like time and cost.

PMID- 27873935
TI  - From Maxwell's Equations to Polarimetric SAR Images: A Simulation Approach.
AB  - A new electromagnetic approach for the simulation of polarimetric SAR images is
      proposed. It starts from Maxwell's equations, employs the spectral domain full
      wave technique, the moment method, and the stationary phase method to compute the
      far electromagnetic fields scattered by multilayer structures. A multilayer
      structure is located at each selected position of a regular rectangular grid of
      coordinates, which defines the scene area under imaging. The grid is determined
      taking into account the elementary scatter size and SAR operational parameters,
      such as spatial resolution, pixel spacing, look angle and platform altitude. A
      two-dimensional separable "sinc" function to represent the SAR spread point
      function is also considered. Multifrequency sets of single-look polarimetric SAR
      images are generated, in L-, C- and X-bands and the images are evaluated using
      several measurements commonly employed in SAR data analysis. The evaluation shows
      that the proposed simulation process is working properly, since the obtained
      results are in accordance with those presented in the literature. Therefore, this
      new approach becomes suitable for carrying out theoretical and practical studies
      using polarimetric SAR images.

PMID- 27873937
TI  - Intracerebroventricular Administration of Amyloid beta-protein Oligomers
      Selectively Increases Dorsal Hippocampal Dialysate Glutamate Levels in the Awake
      Rat.
AB  - Extensive evidence supports an important role for soluble oligomers of the
      amyloid beta-protein (Abeta) in Alzheimer's Disease pathogenesis. In the present
      study we combined intracerebroventricular (icv) injections with brain
      microdialysis technology in the fully conscious rat to assess the effects of icv
      administered SDS-stable low-n Abeta oligomers (principally dimers and trimers) on
      excitatory and inhibitory amino acid transmission in the ipsilateral dorsal
      hippocampus. Microdialysis was employed to assess the effect of icv
      administration of Abeta monomers and Abeta oligomers on dialysate glutamate,
      aspartate and GABA levels in the dorsal hippocampus. Administration of Abeta
      oligomers was associated with a +183% increase (p.

PMID- 27873938
TI  - Sputtered Encapsulation as Wafer Level Packaging for Isolatable MEMS Devices: A
      Technique Demonstrated on a Capacitive Accelerometer.
AB  - This paper discusses sputtered silicon encapsulation as a wafer level packaging
      approach for isolatable MEMS devices. Devices such as accelerometers, RF
      switches, inductors, and filters that do not require interaction with the
      surroundings to function, could thus be fully encapsulated at the wafer level
      after fabrication. A MEMSTech 50g capacitive accelerometer was used to
      demonstrate a sputtered encapsulation technique. Encapsulation with a very
      uniform surface profile was achieved using spin-on glass (SOG) as a sacrificial
      layer, SU-8 as base layer, RF sputtered silicon as main structural layer,
      eutectic gold-silicon as seal layer, and liquid crystal polymer (LCP) as outer
      encapsulant layer. SEM inspection and capacitance test indicated that the movable
      elements were released after encapsulation. Nanoindentation test confirmed that
      the encapsulated device is sufficiently robust to withstand a transfer molding
      process. Thus, an encapsulation technique that is robust, CMOS compatible, and
      economical has been successfully developed for packaging isolatable MEMS devices
      at the wafer level.

PMID- 27873939
TI  - Study of the Relationships between the Spatial Extent of Surface Urban Heat
      Islands and Urban Characteristic Factors Based on Landsat ETM+ Data.
AB  - Ten cities with different population and urban sizes located in the Pearl River
      Delta, Guangdong Province, P.R. China were selected to study the relationships
      between the spatial extent of surface urban heat islands (SUHI) and five urban
      characteristic factors such as urban size, development area, water proportion,
      mean NDVI (Normalized Vegetation Index) and population density, etc. The spatial
      extent of SUHI was quantified by using the hot island area (HIA). All the cities
      are almost at the same latitude, showing similar climate and solar radiation, the
      influence of which could thus be eliminated during our computation and
      comparative study. The land surface temperatures (LST) were retrieved from the
      data of Landsat 7 Enhanced Thematic Mapper Plus (ETM+) band 6 using a mono-window
      algorithm. A variance-segmenting method was proposed to compute HIA for each city
      from the retrieved LST. Factors like urban size, development area and water
      proportion were extracted directly from the classification images of the same
      ETM+ data and the population density factor is from the official census.
      Correlation and regression analyses were performed to study the relationships
      between the HIA and the related factors, and the results show that HIA is highly
      correlated to urban size (r=0.95), population density (r=0.97) and development
      area (r=0.83) in this area. It was also proved that a weak negative correlation
      existed between HIA and both mean NDVI and water proportion for each city. Linear
      functions between HIA and its related factors were established, respectively. The
      HIA can reflect the spatial extent and magnitude of the surface urban heat island
      effect, and can be used as reference in the urban planning.

PMID- 27873940
TI  - Geological Interpretation of PSInSAR Data at Regional Scale.
AB  - Results of a PSInSARTM project carried out by the Regional Agency for
      Environmental Protection (ARPA) in Piemonte Region (Northern Italy) are presented
      and discussed. A methodology is proposed for the interpretation of the PSInSARTM
      data at the regional scale, easy to use by the public administrations and by
      civil protection authorities. Potential and limitations of the PSInSARTM
      technique for ground movement detection on a regional scale and monitoring are
      then estimated in relationship with different geological processes and various
      geological environments.

PMID- 27873941
TI  - Large Scale Environmental Monitoring through Integration of Sensor and Mesh
      Networks.
AB  - Monitoring outdoor environments through networks of wireless sensors has received
      interest for collecting physical and chemical samples at high spatial and
      temporal scales. A central challenge to environmental monitoring applications of
      sensor networks is the short communication range of the sensor nodes, which
      increases the complexity and cost of monitoring commodities that are located in
      geographically spread areas. To address this issue, we propose a new
      communication architecture that integrates sensor networks with medium range
      wireless mesh networks, and provides users with an advanced web portal for
      managing sensed information in an integrated manner. Our architecture adopts a
      holistic approach targeted at improving the user experience by optimizing the
      system performance for handling data that originates at the sensors, traverses
      the mesh network, and resides at the server for user consumption. This holistic
      approach enables users to set high level policies that can adapt the resolution
      of information collected at the sensors, set the preferred performance targets
      for their application, and run a wide range of queries and analysis on both real
      time and historical data. All system components and processes will be described
      in this paper.

PMID- 27873942
TI  - Pattern Recognition via PCNN and Tsallis Entropy.
AB  - In this paper a novel feature extraction method for image processing via PCNN and
      Tsallis entropy is presented. We describe the mathematical model of the PCNN and
      the basic concept of Tsallis entropy in order to find a recognition method for
      isolated objects. Experiments show that the novel feature is translation and
      scale independent, while rotation independence is a bit weak at diagonal angles
      of 45 degrees  and 135 degrees . Parameters of the application on face
      recognition are acquired by bacterial chemotaxis optimization (BCO), and the
      highest classification rate is 72.5%, which demonstrates its acceptable
      performance and potential value.

PMID- 27873943
TI  - A Study on Increasing Sensitivity of Rectangular Microcantilevers Used in
      Biosensors.
AB  - This study proposes a new microcantilever design with a rectangular hole at the
      fixed end of the cantilever that is more sensitive than conventional ones. A
      commercial finite element analysis software ANSYS is used to analyze it. The
      Stoney equation is first used to calculate the surface stress induced moment, and
      then applied to the microcantilever free end to produce deflection. The stress
      analysis of the proposed and conventional designs is performed, followed by
      dynamic analysis of the proposed design. We found that the Sader equation is more
      accurate than Stoney in predicting cantilever deflections, and that for
      increasing the sensitivity of a microcantilever biosensor increasing the
      cantilever thickness is more practical.

PMID- 27873944
TI  - An Open Localization and Local Communication Embodied Sensor.
AB  - In this paper we describe a localization and local communication system which
      allows situated agents to communicate locally, obtaining at the same time both
      the range and the bearing of the emitter without the need of any centralized
      control or any external reference. The system relies on infrared communications
      with frequency modulation and is composed of two interconnected modules for data
      and power measurement. Thanks to the open hardware license under which it is
      released, the research community can easily replicate the system at a low cost
      and/or adapt it for applications in sensor networks and in robotics.

PMID- 27873946
TI  - Sensitive Aflatoxin B1 Determination Using a Magnetic Particles-Based Enzyme
      Linked Immunosorbent Assay.
AB  - A magnetic particle-based enzyme-liked immunosorbent assay (mp-ELISA) has been
      developed as new an alternative immunoassay for Aflatoxin B1 determination. The
      method is based on conventional competitive ELISA whereby the anti-Aflatoxin B1
      antibody is immobilized on the magnetic particles' surface. The influence of the
      antibody type as well as antibody immobilization on the magnetic beads surface
      was investigated in detail. Also, optimum values for the general parameters of
      the method (e.g. tracer concentration, type of antibody, and incubation time)
      were established. Finally, a sensitive immunoassay method (mp-ELISA) was
      performed for Aflatoxin B1 determination at ppt level (LOD = 1 ppt Aflatoxin B1).

PMID- 27873947
TI  - Fine Resolution Air Quality Monitoring from a Small Satellite: CHRIS/PROBA.
AB  - Current remote sensing techniques fail to address the task of air quality
      monitoring over complex regions where multiple pollution sources produce high
      spatial variability. This is due to a lack of suitable satellite-sensor
      combinations and appropriate aerosol optical thickness (AOT) retrieval
      algorithms. The new generation of small satellites, with their lower costs and
      greater flexibility has the potential to address this problem, with customised
      platform-sensor combinations dedicated to monitoring single complex regions or
      mega-cities. This paper demonstrates the ability of the European Space Agency's
      small satellite sensor CHRIS/PROBA to provide reliable AOT estimates at a
      spatially detailed level over Hong Kong, using a modified version of the dense
      dark vegetation (DDV) algorithm devised for MODIS. Since CHRIS has no middle-IR
      band such as the MODIS 2,100 nm band which is transparent to fine aerosols, the
      longest waveband of CHRIS, the 1,019 nm band was used to approximate surface
      reflectance, by the subtraction of an offset derived from synchronous field
      reflectance spectra. Aerosol reflectance in the blue and red bands was then
      obtained from the strong empirical relationship observed between the CHRIS 1,019
      nm, and the blue and red bands respectively. AOT retrievals for three different
      dates were shown to be reliable, when compared with AERONET and Microtops II
      sunphotometers, and a Lidar, as well as air quality data at ground stations. The
      AOT images exhibited considerable spatial variability over the 11 x 11km image
      area and were able to indicate both local and long distance sources.

PMID- 27873945
TI  - Electrochemical Determination of the Antioxidant Potential of Some Less Common
      Fruit Species.
AB  - Various berries and fruit types of less common fruit species are known to contain
      antioxidants. Consumption of high amounts of antioxidant flavonoids, which
      display a variety of biological properties, including antiproliferative and anti
      inflammatory activity, may have a positive impact on human health, particularly
      for the prevention of cancer and other inflammatory diseases. In these studies,
      based on the hypothesis that the fruit extract with the highest content would
      possess significantly higher health benefits, flavonoid-rich extracts were
      obtained from some less common fruit species - Blue Honeysuckles (Lonicera
      Kamtschatica and Lonicera edulis, Turcz. ex. Freyn), Saskatoon berry (Amelanchier
      alnifolia Nutt.) and Chinese Hawthorn (Crataegus pinnatifida BUNGE) - grown from
      germplasm held at the Mendel University of Agriculture and Forestry in Brno,
      Czech Republic and then characterized in terms of biological value based on the
      results from a relative antioxidant capacity assessment. The antioxidant content
      evaluation was based on the total flavonoid amount, determined by liquid
      chromatography with electrochemical detection (HPLC-ED). A DPPH* test was applied
      as a reference. The antioxidant content measured in Chinese Hawthorn fruit
      extract identified it as a potent source of flavonoid antioxidants, with a
      content 9-fold higher than that seen in Amelanchier fruit. The multifunctional
      HPLC-ED array method coupled with a DPPH* reference appears to be the optimal
      analytical progress, accurately reflecting the nutritivetherapeutic properties of
      a fruit.

PMID- 27873948
TI  - Planar Pressure Field Determination in the Initial Merging Zone of an Annular
      Swirling Jet Based on Stereo-PIV Measurements.
AB  - In this paper the static pressure field of an annular swirling jet is measured
      indirectly using stereo-PIV measurements. The pressure field is obtained from
      numerically solving the Poisson equation, taken into account the axisymmetry of
      the flow. At the boundaries no assumptions are made and the exact boundary
      conditions are applied. Since all source terms can be measured using stereo-PIV
      and the boundary conditions are exact, no assumptions other than axisymmetry had
      to be made in the calculation of the pressure field. The advantage of this method
      of indirect pressure measurement is its high spatial resolution compared to the
      traditional pitot probes. Moreover this method is non-intrusive while the
      insertion of a pitot tube disturbs the flow. It is shown that the annular
      swirling flow can be divided into three regimes: a low, an intermediate and a
      high swirling regime. The pressure field of the low swirling regime is the
      superposition of the pressure field of the non-swirling jet and a swirl induced
      pressure field due to the centrifugal forces of the rotating jet. As the swirl
      increases, the swirl induced pressure field becomes dominant and for the
      intermediate and high swirling regimes, the simple radial equilibrium equation
      holds.

PMID- 27873949
TI  - High Precision Signal Processing Algorithm for White Light Interferometry.
AB  - A new signal processing algorithm for absolute temperature measurement using
      white light interferometry has been proposed and investigated theoretically. The
      proposed algorithm determines the phase delay of an interferometer with very high
      precision (.

PMID- 27873950
TI  - Direct-Dispense Polymeric Waveguides Platform for Optical Chemical Sensors.
AB  - We describe an automated robotic technique called direct-dispense to fabricate a
      polymeric platform that supports optical sensor arrays. Direct-dispense, which is
      a type of the emerging direct-write microfabrication techniques, uses fugitive
      organic inks in combination with cross-linkable polymers to create microfluidic
      channels and other microstructures. Specifically, we describe an application of
      direct-dispensing to develop optical biochemical sensors by fabricating planar
      ridge waveguides that support sol-gelderived xerogel-based thin films. The
      xerogel-based sensor materials act as host media to house luminophore biochemical
      recognition elements. As a prototype implementation, we demonstrate gaseous
      oxygen (O2) responsive optical sensors that operate on the basis of monitoring
      luminescence intensity signals. The optical sensor employs a Light Emitting Diode
      (LED) excitation source and a standard silicon photodiode as the detector. The
      sensor operates over the full scale (0%-100%) of O2 concentrations with a
      response time of less than 1 second. This work has implications for the
      development of miniaturized multisensor platforms that can be cost-effectively
      and reliably mass-produced.

PMID- 27873952
TI  - A Novel Sensor System for Measuring Wheel Loads of Vehicles on Highways.
AB  - With the development of the highway transportation and business trade, vehicle
      Weigh-In-Motion (WIM) technology has become a key technology for measuring
      traffic loads. In this paper a novel WIM system based on monitoring of pavement
      strain responses in rigid pavement was investigated. In this WIM system multiple
      low cost, light weight, small volume and high accuracy embedded concrete strain
      sensors were used as WIM sensors to measure rigid pavement strain responses. In
      order to verify the feasibility of the method, a system prototype based on
      multiple sensors was designed and deployed on a relatively busy freeway. Field
      calibration and tests were performed with known two-axle truck wheel loads and
      the measurement errors were calculated based on the static weights measured with
      a static weighbridge. This enables the weights of other vehicles to be calculated
      from the calibration constant. Calibration and test results for individual
      sensors or three-sensor fusions are both provided. Repeatability, sources of
      error, and weight accuracy are discussed. Successful results showed that the
      proposed method was feasible and proven to have a high accuracy. Furthermore, a
      sample mean approach using multiple fused individual sensors could provide better
      performance compared to individual sensors.

PMID- 27873953
TI  - Energy Harvesting Chip and the Chip Based Power Supply Development for a Wireless
      Sensor Network.
AB  - In this study, an energy harvesting chip was developed to scavenge energy from
      artificial light to charge a wireless sensor node. The chip core is a miniature
      transformer with a nano-ferrofluid magnetic core. The chip embedded transformer
      can convert harvested energy from its solar cell to variable voltage output for
      driving multiple loads. This chip system yields a simple, small, and more
      importantly, a battery-less power supply solution. The sensor node is equipped
      with multiple sensors that can be enabled by the energy harvesting power supply
      to collect information about the human body comfort degree. Compared with lab
      instruments, the nodes with temperature, humidity and photosensors driven by
      harvested energy had variation coefficient measurement precision of less than 6%
      deviation under low environmental light of 240 lux. The thermal comfort was
      affected by the air speed. A flow sensor equipped on the sensor node was used to
      detect airflow speed. Due to its high power consumption, this sensor node
      provided 15% less accuracy than the instruments, but it still can meet the
      requirement of analysis for predicted mean votes (PMV) measurement. The energy
      harvesting wireless sensor network (WSN) was deployed in a 24-hour convenience
      store to detect thermal comfort degree from the air conditioning control. During
      one year operation, the sensor network powered by the energy harvesting chip
      retained normal functions to collect the PMV index of the store. According to the
      one month statistics of communication status, the packet loss rate (PLR) is 2.3%,
      which is as good as the presented results of those WSNs powered by battery.
      Referring to the electric power records, almost 54% energy can be saved by the
      feedback control of an energy harvesting sensor network. These results illustrate
      that, scavenging energy not only creates a reliable power source for electronic
      devices, such as wireless sensor nodes, but can also be an energy source by
      building an energy efficient program.

PMID- 27873954
TI  - Assessment of Polarimetric SAR Interferometry for Improving Ship Classification
      based on Simulated Data.
AB  - This paper uses a complete and realistic SAR simulation processing chain,
      GRECOSAR, to study the potentialities of Polarimetric SAR Interferometry
      (POLInSAR) in the development of new classification methods for ships. Its high
      processing efficiency and scenario flexibility have allowed to develop exhaustive
      scattering studies. The results have revealed, first, vessels' geometries can be
      described by specific combinations of Permanent Polarimetric Scatterers (PePS)
      and, second, each type of vessel could be characterized by a particular spatial
      and polarimetric distribution of PePS. Such properties have been recently
      exploited to propose a new Vessel Classification Algorithm (VCA) working with
      POLInSAR data, which, according to several simulation tests, may provide
      promising performance in real scenarios. Along the paper, explanation of the main
      steps summarizing the whole research activity carried out with ships and GRECOSAR
      are provided as well as examples of the main results and VCA validation tests.
      Special attention will be devoted to the new improvements achieved, which are
      related to simulations processing a new and highly realistic sea surface model.
      The paper will show that, for POLInSAR data with fine resolution, VCA can help to
      classify ships with notable robustness under diverse and adverse observation
      conditions.

PMID- 27873951
TI  - Polarographic Electrode Measures of Cerebral Tissue Oxygenation: Implications for
      Functional Brain Imaging.
AB  - The changes in blood flow, blood volume and oxygenation that accompany focal
      increases in neural activity are collectively referred to as the hemodynamic
      response and form the basis of non-invasive neuroimaging techniques such as blood
      oxygen level dependent (BOLD) functional magnetic resonance imaging. A principle
      factor influencing blood oxygenation, the cerebral metabolic rate of oxygen
      consumption is poorly understood and as such, data from imaging techniques are
      difficult to interpret in terms of the underlying neural activity. In particular
      how neurometabolic changes vary temporally, spatially and in magnitude remains
      uncertain. Furthermore knowledge of which aspects of neural activity are closely
      reflected by metabolic changes is essential for the correct interpretation of
      cognitive neuroscience studies in terms of information processing. Polarographic
      electrode measurements of cerebral tissue oxygenation in animal models following
      presentation of sensory stimuli have started to address these issues. Early
      studies demonstrated both increases and decreases in tissue oxygenation following
      neural activation. However a recent series of elegant studies in the cat visual
      system demonstrated a tight spatial and temporal coupling between evoked peri
      synaptic activity and oxygen consumption following presentation of visual
      stimuli.

PMID- 27873955
TI  - Cosmic Influence on the Sun-Earth Environment.
AB  - SOHO satellite data reveals geophysical changes before sudden changes in the
      Earth's Sun-Earth environment. The influence of extragalactic changes on the Sun
      as well as the Sun-Earth environment seems to be both periodic and episodic. The
      periodic changes in terms of solar maxima and minima occur every 11 years,
      whereas the episodic changes can happen at any time. Episodic changes can be
      monitored by cosmic ray detectors as a sudden increase or decrease of activity.
      During these solar and cosmic anomaly periods the environment of the Earth is
      affected. The Star-Sun-Earth connection has the potential to influence the
      thermosphere, atmosphere, ionosphere and lithosphere. Initial correlation of the
      cosmic and Sun-Earth connection has shown the possibility of predicting
      earthquakes, sudden changes in atmospheric temperatures and erratic
      rainfall/snowfall patterns.

PMID- 27873956
TI  - An Energy-Efficient Secure Routing and Key Management Scheme for Mobile Sinks in
      Wireless Sensor Networks Using Deployment Knowledge.
AB  - For many sensor network applications such as military or homeland security, it is
      essential for users (sinks) to access the sensor network while they are moving.
      Sink mobility brings new challenges to secure routing in large-scale sensor
      networks. Previous studies on sink mobility have mainly focused on efficiency and
      effectiveness of data dissemination without security consideration. Also, studies
      and experiences have shown that considering security during design time is the
      best way to provide security for sensor network routing. This paper presents an
      energy-efficient secure routing and key management for mobile sinks in sensor
      networks, called SCODEplus. It is a significant extension of our previous study
      in five aspects: (1) Key management scheme and routing protocol are considered
      during design time to increase security and efficiency; (2) The network topology
      is organized in a hexagonal plane which supports more efficiency than previous
      square-grid topology; (3) The key management scheme can eliminate the impacts of
      node compromise attacks on links between non-compromised nodes; (4) Sensor node
      deployment is based on Gaussian distribution which is more realistic than uniform
      distribution; (5) No GPS or like is required to provide sensor node location
      information. Our security analysis demonstrates that the proposed scheme can
      defend against common attacks in sensor networks including node compromise
      attacks, replay attacks, selective forwarding attacks, sinkhole and wormhole,
      Sybil attacks, HELLO flood attacks. Both mathematical and simulation-based
      performance evaluation show that the SCODEplus significantly reduces the
      communication overhead, energy consumption, packet delivery latency while it
      always delivers more than 97 percent of packets successfully.

PMID- 27873957
TI  - Field Calibration of Wind Direction Sensor to the True North and Its Application
      to the Daegwanryung Wind Turbine Test Sites.
AB  - This paper proposes a field calibration technique for aligning a wind direction
      sensor to the true north. The proposed technique uses the synchronized
      measurements of captured images by a camera, and the output voltage of a wind
      direction sensor. The true wind direction was evaluated through image processing
      techniques using the captured picture of the sensor with the least square sense.
      Then, the evaluated true value was compared with the measured output voltage of
      the sensor. This technique solves the discordance problem of the wind direction
      sensor in the process of installing meteorological mast. For this proposed
      technique, some uncertainty analyses are presented and the calibration accuracy
      is discussed. Finally, the proposed technique was applied to the real
      meteorological mast at the Daegwanryung test site, and the statistical analysis
      of the experimental testing estimated the values of stable misalignment and
      uncertainty level. In a strict sense, it is confirmed that the error range of the
      misalignment from the exact north could be expected to decrease within the
      credibility level.

PMID- 27873958
TI  - An Annual Plant Growth Proxy in the Mojave Desert Using MODIS-EVI Data.
AB  - In the arid Mojave Desert, the phenological response of vegetation is largely
      dependent upon the timing and amount of rainfall, and maps of annual plant cover
      at any one point in time can vary widely. Our study developed relative annual
      plant growth models as proxies for annual plant cover using metrics that captured
      phenological variability in Moderate-Resolution Imaging Spectroradiometer (MODIS)
      Enhanced Vegetation Index (EVI) satellite images. We used landscape phenologies
      revealed in MODIS data together with ecological knowledge of annual plant
      seasonality to develop a suite of metrics to describe annual growth on a yearly
      basis. Each of these metrics was applied to temporally-composited MODIS-EVI
      images to develop a relative model of annual growth. Each model was evaluated by
      testing how well it predicted field estimates of annual cover collected during
      2003 and 2005 at the Mojave National Preserve. The best performing metric was the
      spring difference metric, which compared the average of three spring MODIS-EVI
      composites of a given year to that of 2002, a year of record drought. The spring
      difference metric showed correlations with annual plant cover of R2 = 0.61 for
      2005 and R2 = 0.47 for 2003. Although the correlation is moderate, we consider it
      supportive given the characteristics of the field data, which were collected for
      a different study in a localized area and are not ideal for calibration to MODIS
      pixels. A proxy for annual growth potential was developed from the spring
      difference metric of 2005 for use as an environmental data layer in desert
      tortoise habitat modeling. The application of the spring difference metric to
      other imagery years presents potential for other applications such as fuels,
      invasive species, and dust-emission monitoring in the Mojave Desert.

PMID- 27873959
TI  - Selecting Map Projections in Minimizing Area Distortions in GIS Applications.
AB  - Varioussoftware for Geographical Information Systems (GISs) have been developed
      and used in many different engineering projects. In GIS applications, map
      coverage is important in terms of performing reliable and meaningful queries. Map
      projections can be conformal, equal-area and equidistant. The goal of an
      application plays an important role in choosing one of those projections.
      Choosing the equal-area projection for an application in which area information
      is used (forestry, agriculture, ecosystem etc) reduces the amount of distortion
      on the area, but many users using GIS ignore this fact and continue to use
      applications with present map sheets no matter in what map projection it is. For
      example, extracting area information from data whose country system's map sheet
      is in conformal projection is relatively more distorted, compared to an equal
      area projection one. The goal of this study is to make the best decision in
      choosing the most proper equal-area projection among the choices provided by
      ArcGIS 9.0, which is a popular GIS software package, and making a comparison on
      area errors when conformal projection is used. In this study, the area of parcels
      chosen in three different regions and geographic coordinates and whose sizes vary
      between 0.01 to 1,000,000 ha are calculated according to Transversal Mercator
      (TM, 3 degrees ), Universal Transversal Mercator (UTM, 6 degrees ) and 14
      different equal-area projections existing in the ArcGIS 9.0 GIS software package.
      The parcel areas calculated with geographical coordinates are accepted as
      definite. The difference between the sizes calculated according to projection
      coordinates and real sizes of the parcels are determined. Consequently, the
      appropriate projections are decided for the areas smaller and equal than 1,000 ha
      and greater than 1,000 ha in the GIS software package.

PMID- 27873960
TI  - Raman Tweezers as a Diagnostic Tool of Hemoglobin-Related Blood Disorders.
AB  - This review presents the development of a Raman Tweezers system for detecting
      hemoglobin-related blood disorders at a single cell level. The study demonstrates
      that the molecular fingerprint insight provided by Raman analysis holds great
      promise for distinguishing between healthy and diseased cells in the field of
      biomedicine. Herein a Raman Tweezers system has been applied to investigate the
      effects of thalassemia, a blood disease quite diffuse in the Mediterranean Sea
      region. By resonant excitation of hemoglobin Raman bands, we examined the
      oxygenation capability of normal, alpha- and beta-thalassemic erythrocytes. A
      reduction of this fundamental red blood cell function, particularly severe for
      beta-thalassemia, has been found. Raman spectroscopy was also used to draw
      hemoglobin distribution inside single erythrocytes; the results confirmed the
      characteristic anomaly (target shape), occurring in thalassemia and some other
      blood disorders. The success of resonance Raman spectroscopy for thalassemia
      detection reported in this review provide an interesting starting point to
      explore the application of a Raman Tweezers system in the analysis of several
      blood disorders.

PMID- 27873961
TI  - Design and Validation of a Ten-Port Waveguide Reflectometer Sensor: Application
      to Efficiency Measurement and Optimization of Microwave-Heating Ovens.
AB  - This work presents the design, manufacturing process, calibration and validation
      of a new microwave ten-port waveguide reflectometer based on the use of neural
      networks. This low-cost novel device solves some of the shortcomings of previous
      reflectometers such as non-linear behavior of power sensors, noise presence and
      the complexity of the calibration procedure, which is often based on complex
      mathematical equations. These problems, which imply the reduction of the
      reflection coefficient measurement accuracy, have been overcome by using a higher
      number of probes than usual six-port configurations and by means of the use of
      Radial Basis Function (RBF) neural networks in order to reduce the influence of
      noise and non-linear processes over the measurements. Additionally, this sensor
      can be reconfigured whenever some of the eight coaxial power detectors fail,
      still providing accurate values in real time. The ten-port performance has been
      compared against a high-cost measurement instrument such as a vector network
      analyzer and applied to the measurement and optimization of energy efficiency of
      microwave ovens, with good results.

PMID- 27873962
TI  - Coupling a Neural Network-Based forward Model and a Bayesian Inversion Approach
      to Retrieve Wind Field from Spaceborne Polarimetric Radiometers.
AB  - A simulation study to assess the potentiality of sea surface wind vector
      estimation based on the approximation of the forward model through Neural
      Networks and on the Bayesian theory of parameter estimation is presented. A
      polarimetric microwave radiometer has been considered and its observations have
      been simulated by means of the two scale model. To perform the simulations, the
      atmospheric and surface parameters have been derived from ECMWF analysis fields.
      To retrieve wind speed, Minimum Variance (MV) and Maximum Posterior Probability
      (MAP) criteria have been used while, for wind direction, a Maximum Likelihood
      (ML) criterion has been exploited. To minimize the cost function of MAP and ML,
      conventional Gradient Descent method, as well as Simulated Annealing optimization
      technique, have been employed. Results have shown that the standard deviation of
      the wind speed retrieval error is approximately 1.1 m/s for the best estimator.
      As for the wind direction, the standard deviation of the estimation error is less
      than 13 degrees  for wind speeds larger than 6 m/s. For lower wind velocities,
      the wind direction signal is too weak to ensure reliable retrievals. A method to
      deal with the non-uniqueness of the wind direction solution has been also
      developed. A test on a case study has yielded encouraging results.

PMID- 27873963
TI  - A Novel Re-keying Function Protocol (NRFP) For Wireless Sensor Network Security.
AB  - This paper describes a novel re-keying function protocol (NRFP) for wireless
      sensor network security. A re-keying process management system for sensor
      networks is designed to support in-network processing. The design of the protocol
      is motivated by decentralization key management for wireless sensor networks
      (WSNs), covering key deployment, key refreshment, and key establishment. NRFP
      supports the establishment of novel administrative functions for sensor nodes
      that derive/re-derive a session key for each communication session. The protocol
      proposes direct connection, in-direct connection and hybrid connection. NRFP also
      includes an efficient protocol for local broadcast authentication based on the
      use of one-way key chains. A salient feature of the authentication protocol is
      that it supports source authentication without precluding in-network processing.
      Security and performance analysis shows that it is very efficient in computation,
      communication and storage and, that NRFP is also effective in defending against
      many sophisticated attacks.

PMID- 27873964
TI  - Problems Encountered in Fluctuating Flame Temperature Measurements by
      Thermocouple.
AB  - Some thermocouple experiments were carried out in order to obtain sensitivity of
      thermocouple readings to fluctuations in flames and to determine if the average
      thermocouple reading was representative of the local volume temperature for
      fluctuating flames. The thermocouples considered were an exposed junction
      thermocouple and a fully sheathed thermocouple with comparable time constants.
      Either the voltage signal or indicated temperature for each test was recorded at
      sampling rates between 300-4,096 Hz. The trace was then plotted with respect to
      time or sample number so that time variation in voltage or temperature could be
      visualized and the average indicated temperature could be determined. For
      experiments where high sampling rates were used, the signal was analyzed using
      Fast Fourier Transforms (FFT) to determine the frequencies present in the
      thermocouple signal. This provided a basic observable as to whether or not the
      probe was able to follow flame oscillations. To enhance oscillations, for some
      experiments, the flame was forced. An analysis based on thermocouple time
      constant, coupled with the transfer function for a sinusoidal input was tested
      against the experimental results.

PMID- 27873965
TI  - Vesicles for Signal Amplification in a Biosensor for the Detection of Low Antigen
      Concentrations.
AB  - The sensitivity of biosensors is often not sufficient to detect diagnostically
      relevant biomarker concentrations. In this paper we have utilized a Quartz
      Crystal Microbalance with Dissipation monitoring (QCM-D) to detect dissipative
      losses induced by the attachment of intact vesicles. We modified a sandwich assay
      by coupling the secondary antibodies to vesicles. This resulted in an increase of
      detection sensitivity, achieving a diagnostically relevant detection limit of 5
      ng/ml or 30 pM antigens. In addition, we could combine the individual assay steps
      to decrease the total time to result in about 30 minutes.

PMID- 27873966
TI  - Zeolite-based Impedimetric Gas Sensor Device in Low-cost Technology for
      Hydrocarbon Gas Detection.
AB  - Due to increasing environmental concerns the need for inexpensive selective gas
      sensors is increasing. This work deals with transferring a novel zeolite-based
      impedimetric hydrocarbon gas sensor principle, which has been originally
      manufactured in a costly combination of photolithography, thin-film processes,
      and thick-film processes to a lowcost technology comprising only thick-film
      processes and one electroplating step. The sensing effect is based on a thin
      chromium oxide layer between the interdigital electrodes and a Pt-loaded ZSM-5
      zeolite film. When hydrocarbons are present in the sensor ambient, the electrical
      sensor impedance increases strongly and selectively. In the present work, the
      chromium oxide film is electroplated on Au screen-printed interdigital electrodes
      and then oxidized to Cr2O3. The electrode area is covered with the screen-printed
      zeolite. The sensor device is self-heated utilizing a planar platinum heater on
      the backside. The best sensor performance is obtained at a frequency of 3 Hz at
      around 350  degrees C. The good selectivity of the original sensor setup could be
      confirmed, but a strong cross-sensitivity to ammonia occurs, which might prohibit
      its original intention for use in automotive exhausts.

PMID- 27873967
TI  - A Love Wave Reflective Delay Line with Polymer Guiding Layer for Wireless Sensor
      Application.
AB  - This paper presents an optimal design for a Love wave reflective delay line on
      41o YX LiNbO3 with a polymer guiding layer for wireless sensor applications. A
      theoretical model was established to describe the Love wave propagation along the
      larger piezoelectric substrate with polymer waveguide, and the lossy mechanism
      from the viscoelastic waveguide was discussed, which results in the optimal
      guiding layer thickness. Coupling of modes (COM) was used to determine the
      optimal design parameters of the reflective delay line structured by single phase
      unidirectional transducers (SPUDTs) and shorted grating reflectors. Using the
      network analyzer, the fabricated Love wave reflective delay line was
      characterized, high signal noise ratio (S/N), sharp reflection peaks, and few
      spurious noise between the peaks were found, and the measured result agrees well
      with the simulated one. Also, the optimal guiding layer thickness of 1.5~1.8MUm
      was extracted experimentally, and it is consistent with the theoretical analysis.

PMID- 27873968
TI  - TinyONet: A Cache-Based Sensor Network Bridge Enabling Sensing Data Reusability
      and Customized Wireless Sensor Network Services.
AB  - In recent years, a few protocol bridge research projects have been announced to
      enable a seamless integration of Wireless Sensor Networks (WSNs) with the TCP/IP
      network. These studies have ensured the transparent end-to-end communication
      between two network sides in the node-centric manner. Researchers expect this
      integration will trigger the development of various application domains. However,
      prior research projects have not fully explored some essential features for WSNs,
      especially the reusability of sensing data and the data-centric communication. To
      resolve these issues, we suggested a new protocol bridge system named TinyONet.
      In TinyONet, virtual sensors play roles as virtual counterparts of physical
      sensors and they dynamically group to make a functional entity, Slice. Instead of
      direct interaction with individual physical sensors, each sensor application uses
      its own WSN service provided by Slices. If a new kind of service is required in
      TinyONet, the corresponding function can be dynamically added at runtime. Beside
      the data-centric communication, it also supports the node-centric communication
      and the synchronous access. In order to show the effectiveness of the system, we
      implemented TinyONet on an embedded Linux machine and evaluated it with several
      experimental scenarios.

PMID- 27873970
TI  - Horizontal Positional Accuracy of Google Earth's High-Resolution Imagery Archive.
AB  - Google Earth now hosts high-resolution imagery that spans twenty percent of the
      Earth's landmass and more than a third of the human population. This contemporary
      highresolution archive represents a significant, rapidly expanding, cost-free and
      largely unexploited resource for scientific inquiry. To increase the scientific
      utility of this archive, we address horizontal positional accuracy
      (georegistration) by comparing Google Earth with Landsat GeoCover scenes over a
      global sample of 436 control points located in 109 cities worldwide. Landsat
      GeoCover is an orthorectified product with known absolute positional accuracy of
      less than 50 meters root-mean-squared error (RMSE). Relative to Landsat GeoCover,
      the 436 Google Earth control points have a positional accuracy of 39.7 meters
      RMSE (error magnitudes range from 0.4 to 171.6 meters). The control points
      derived from satellite imagery have an accuracy of 22.8 meters RMSE, which is
      significantly more accurate than the 48 control-points based on aerial
      photography (41.3 meters RMSE; t-test p-value < 0.01). The accuracy of control
      points in more-developed countries is 24.1 meters RMSE, which is significantly
      more accurate than the control points in developing countries (44.4 meters RMSE;
      t-test p-value < 0.01). These findings indicate that Google Earth highresolution
      imagery has a horizontal positional accuracy that is sufficient for assessing
      moderate-resolution remote sensing products across most of the world's peri-urban
      areas.

PMID- 27873971
TI  - A Passive Wireless Temperature Sensor for Harsh Environment Applications.
AB  - High temperature sensors capable of operating in harsh environments are needed in
      order to prevent disasters caused by structural or system functional failures due
      to increasing temperatures. Most existing temperature sensors do not satisfy the
      needs because they require either physical contact or a battery power supply for
      signal communication, and furthermore, neither of them can withstand high
      temperatures nor rotating applications. This paper presents a novel passive
      wireless temperature sensor, suitable for working in harsh environments for high
      temperature rotating component monitoring. A completely passive LC resonant
      telemetry scheme, relying on a frequency variation output, which has been applied
      successfully in pressure, humidity and chemical measurement, is integrated with a
      unique high-k temperature sensitive ceramic material, in order to measure the
      temperatures without contacts, active elements, or power supplies within the
      sensor. In this paper, the high temperature sensor design and performance
      analysis are conducted based on mechanical and electrical modeling, in order to
      maximize the sensing distance, the Q factor and the sensitivity. In the end, the
      sensor prototype is fabricated and calibrated successfully up to 235oC, so that
      the concept of temperature sensing through passive wireless communication is
      proved.

PMID- 27873969
TI  - Optoelectronic Plethysmography has Improved our Knowledge of Respiratory
      Physiology and Pathophysiology.
AB  - It is well known that the methods actually used to track thoraco-abdominal volume
      displacement have several limitations. This review evaluates the clinical
      usefulness of measuring chest wall kinematics by optoelectronic plethysmography
      [OEP]. OEP provides direct measurements (both absolute and its variations) of the
      volume of the chest wall and its compartments, according to the model of Ward and
      Macklem, without requiring calibration or subject cooperation. The system is non
      invasive and does not require a mouthpiece or nose-clip which may modify the
      pattern of breathing, making the subject aware of his breathing. Also, the
      precise assessment of compartmental changes in chest wall volumes, combined with
      pressure measurements, provides a detailed description of the action and control
      of the different respiratory muscle groups and assessment of chest wall dynamics
      in a number of physiological and clinical experimental conditions.

PMID- 27873972
TI  - Sparse Detector Imaging Sensor with Two-Class Silhouette Classification.
AB  - This paper presents the design and test of a simple active near-infrared sparse
      detector imaging sensor. The prototype of the sensor is novel in that it can
      capture remarkable silhouettes or profiles of a wide-variety of moving objects,
      including humans, animals, and vehicles using a sparse detector array comprised
      of only sixteen sensing elements deployed in a vertical configuration. The
      prototype sensor was built to collect silhouettes for a variety of objects and to
      evaluate several algorithms for classifying the data obtained from the sensor
      into two classes: human versus non-human. Initial tests show that the
      classification of individually sensed objects into two classes can be achieved
      with accuracy greater than ninety-nine percent (99%) with a subset of the sixteen
      detectors using a representative dataset consisting of 512 signatures. The
      prototype also includes a Webservice interface such that the sensor can be tasked
      in a network-centric environment. The sensor appears to be a low-cost alternative
      to traditional, high-resolution focal plane array imaging sensors for some
      applications. After a power optimization study, appropriate packaging, and
      testing with more extensive datasets, the sensor may be a good candidate for
      deployment in vast geographic regions for a myriad of intelligent electronic
      fence and persistent surveillance applications, including perimeter security
      scenarios.

PMID- 27873973
TI  - Retrieval of Surface Air Specific Humidity Over the Ocean Using AMSR-E
      Measurements.
AB  - We have developed a new algorithm to estimate the surface air specific humidity
      over the ocean from AMSR-E data. It should be noted that remarkably reduced
      random errors of the estimated surface air specific humidity result from using
      the surface air specific humidity provided by reanalysis data. We validated our
      new algorithm using independent ship and buoy data. The bias, RMS error, and
      correlation coefficient of the products obtained using our algorithm for global
      buoys are 0.38 g/kg, 0.61 g/kg and 0.99, respectively. It should be noted that
      surface specific humidity having similar accuracy to the reanalysis data near in
      situ data could be derived from AMSR-E data by the present algorithm.

PMID- 27873974
TI  - Measurements of Impedance and Attenuation at CENELEC Bands for Power Line
      Communications Systems.
AB  - Power line impedance is a very important parameter on the design of power line
      communications (PLC) modem architecture. Variations on the impedance of the power
      line affect the communications circuit performance. In order to determine
      impedance of the power lines, measurements were carried out in Turkey at
      frequencies ranging from 10 to 170 kHz, (CENELEC A,B,C,D bands). Measurements
      were conducted in three categories: rural, urban and the industrial power lines.
      Experimental results are presented in graphical form. The measured impedances
      were determined as 3-17 ohms, 1-17 ohms, and 1-21 ohms for rural, urban and the
      industrial lines, respectively. A set of the formulas between impedance and
      frequency are developed on the power lines using the regression analysis from the
      obtained empirical data. Signal attenuations on the power lines in the CENELEC
      band are also measured for rural, urban and industrial regions. Attenuation
      measurements are repeated for phase-neutral, phase-ground and the neutral-ground
      conductors. Signal attenuations are found to be 4-30 dB, for different power
      lines. To establish validity of obtained results for the design of PLC systems,
      the results are compared with previous investigations. The effects of some
      household appliances such as TV, PC, UPS, lighting and cooling systems on the
      impedances and the attenuations for power line communications systems are
      observed. Some suggestions and proposals are presented for PLC modem designers.

PMID- 27873975
TI  - Energy Options for Wireless Sensor Nodes.
AB  - Reduction in size and power consumption of consumer electronics has opened up
      many opportunities for low power wireless sensor networks. One of the major
      challenges is in supporting battery operated devices as the number of nodes in a
      network grows. The two main alternatives are to utilize higher energy density
      sources of stored energy, or to generate power at the node from local forms of
      energy. This paper reviews the state-of-the art technology in the field of both
      energy storage and energy harvesting for sensor nodes. The options discussed for
      energy storage include batteries, capacitors, fuel cells, heat engines and
      betavoltaic systems. The field of energy harvesting is discussed with reference
      to photovoltaics, temperature gradients, fluid flow, pressure variations and
      vibration harvesting.

PMID- 27873976
TI  - Spectral and Spatial-Based Classification for Broad-Scale Land Cover Mapping
      Based on Logistic Regression.
AB  - Improvement of satellite sensor characteristics motivates the development of new
      techniques for satellite image classification. Spatial information seems to be
      critical in classification processes, especially for heterogeneous and complex
      landscapes such as those observed in the Mediterranean basin. In our study, a
      spectral classification method of a LANDSAT-5 TM imagery that uses several
      binomial logistic regression models was developed, evaluated and compared to the
      familiar parametric maximum likelihood algorithm. The classification approach
      based on logistic regression modelling was extended to a contextual one by using
      autocovariates to consider spatial dependencies of every pixel with its
      neighbours. Finally, the maximum likelihood algorithm was upgraded to contextual
      by considering typicality, a measure which indicates the strength of class
      membership. The use of logistic regression for broad-scale land cover
      classification presented higher overall accuracy (75.61%), although not
      statistically significant, than the maximum likelihood algorithm (64.23%), even
      when the latter was refined following a spatial approach based on Mahalanobis
      distance (66.67%). However, the consideration of the spatial autocovariate in the
      logistic models significantly improved the fit of the models and increased the
      overall accuracy from 75.61% to 80.49%.

PMID- 27873977
TI  - Globally Optimal Multisensor Distributed Random Parameter Matrices Kalman
      Filtering Fusion with Applications.
AB  - This paper proposes a new distributed Kalman filtering fusion with random state
      transition and measurement matrices, i.e., random parameter matrices Kalman
      filtering. It is proved that under a mild condition the fused state estimate is
      equivalent to the centralized Kalman filtering using all sensor measurements;
      therefore, it achieves the best performance. More importantly, this result can be
      applied to Kalman filtering with uncertain observations including the measurement
      with a false alarm probability as a special case, as well as, randomly variant
      dynamic systems with multiple models. Numerical examples are given which support
      our analysis and show significant performance loss of ignoring the randomness of
      the parameter matrices.

PMID- 27873978
TI  - Land Use/Cover Dynamics in Response to Changes in Environmental and Socio
      Political Forces in the Upper Reaches of Yangtze River, China.
AB  - Land use/cover change (LUCC), which results from the complex interaction of
      social, ecological and geophysical processes, is a major issue and the main cause
      of global environmental change. This study analyzed the land use/cover dynamics
      and their environmental and socio-political forces in the upper reaches of
      Yangtze River from 1980 to 2000 by using remote sensing, climatic and socio
      economic data from both research institutes and government departments. The
      results indicated that there had been significant land use/cover changes between
      1980 and 2000 in the study area, which were characterized by a severe replacement
      of cropland and woodland with grassland and built-up land. The transition
      matrices highlight the dominant dynamic events and the internal conversions
      between land use/cover types during the study period and reveal two distinct
      transition phases. Land use/cover changes in the upper reaches of Yangtze River
      during 1980 to 2000, while restricted by environmental attributes, were strongly
      driven by socio-political factors. However, excessively pursuing higher land use
      benefits likely results in serious environmental degradation. This study suggests
      that the restructuring of land use should be based on land suitability and
      sustainable protection of fragile environment in the upper reaches of Yangtze
      River. A thorough comprehension of historical changes will enhance our capability
      to predict future land use change and contribute to effective management
      strategies and policies for the rational land use.

PMID- 27873979
TI  - Wireless Monitoring of Automobile Tires for Intelligent Tires.
AB  - This review discusses key technologies of intelligent tires focusing on sensors
      and wireless data transmission. Intelligent automobile tires, which monitor their
      pressure, deformation, wheel loading, friction, or tread wear, are expected to
      improve the reliability of tires and tire control systems. However, in installing
      sensors in a tire, many problems have to be considered, such as compatibility of
      the sensors with tire rubber, wireless transmission, and battery installments. As
      regards sensing, this review discusses indirect methods using existing sensors,
      such as that for wheel speed, and direct methods, such as surface acoustic wave
      sensors and piezoelectric sensors. For wireless transmission, passive wireless
      methods and energy harvesting are also discussed.

PMID- 27873980
TI  - Use of Automatic Target Recognition System for the Displacement Measurements in a
      Small Diameter Tunnel Ahead of the Face of the Motorway Tunnel During Excavation.
AB  - During construction of the Sentvid tunnel a unique opportunity arose to measure
      the 3D displacements ahead of the motorway tunnel excavation face, since the
      exploratory tunnel was already constructed in the axis of the main tunnel.
      According to reviewed literature such measurements had not been performed yet and
      several problems regarding equipment and complete scheme of the experiment needed
      to be overcome. The paper gives a brief description of the Sentvid tunnel
      project, presents significant factors that affected the choice of the geodetic
      equipment and describes the scheme of the experiment. A special attention is
      focused on the problems relating to the operation of the instrument in demanding
      environmental conditions (water, dust).

PMID- 27873981
TI  - Water Productivity Mapping (WPM) Using Landsat ETM+ Data for the Irrigated
      Croplands of the Syrdarya River Basin in Central Asia.
AB  - The overarching goal of this paper was to espouse methods and protocols for water
      productivity mapping (WPM) using high spatial resolution Landsat remote sensing
      data. In a world where land and water for agriculture are becoming increasingly
      scarce, growing "more crop per drop" (increasing water productivity) becomes
      crucial for food security of future generations. The study used time-series
      Landsat ETM+ data to produce WPMs of irrigated crops, with emphasis on cotton in
      the Galaba study area in the Syrdarya river basin of Central Asia. The WPM
      methods and protocols using remote sensing data consisted of: (1) crop
      productivity (ton/ha) maps (CPMs) involvingcrop type classification, crop yield
      and biophysical modeling, and extrapolating yield models to larger areas using
      remotely sensed data; (2) crop water use (m3/ha) maps (WUMs) (or actual seasonal
      evapotranspiration or actual ET) developed through Simplified Surface Energy
      Balance (SSEB) model; and (3) water productivity (kg/m3) maps (WPMs) produced by
      dividing raster layers of CPMs by WUMs. The SSEB model calculated WUMs (actual
      ET) by multiplying the ET fractionby reference ET. The ETfraction was determined
      using Landsat thermal imagery by selecting the "hot" pixels (zero ET) and "cold"
      pixels (maximum ET). The grass reference ET was calculated by FAO Penman-Monteith
      method using meteorological data. The WPMs for the Galaba study area demonstrated
      a wide variations (0-0.54 kg/m3) in water productivity of cotton fields with
      overwhelming proportion (87%) of the area having WP less than 0.30 kg/m3, 11% of
      the area having WP in range of 0.30-0.36 kg/m3, and only 2% of the area with WP
      greater than 0.36 kg/m3. These results clearly imply that there are opportunities
      for significant WP increases in overwhelming proportion of the existing
      croplands. The areas of low WP are spatially pin-pointed and can be used as focus
      for WP improvements through better land and water management practices.

PMID- 27873982
TI  - Inversion of Electromagnetic Models for Bare Soil Parameter Estimation from
      Multifrequency Polarimetric SAR Data.
AB  - The potentiality of polarimetric SAR data for the estimation of bare soil
      geophysical parameters (i.e., roughness and soil moisture) is investigated in
      this work. For this purpose, two forward models available in the literature, able
      to simulate the measurements of a multifrequency radar polarimeter, have been
      implemented for use within an inversion scheme. A multiplicative noise has been
      considered in the multidimensional space of the elements of the polarimetric
      Covariance Matrix, by adopting a complex Wishart distribution to account for
      speckle effects. An additive error has been also introduced on the simulated
      measurements to account for calibration and model errors. Maximum a Posteriori
      Probability and Minimum Variance criteria have been considered to perform the
      inversion. As for the algorithms to implement the criteria, simple
      optimization/integration procedures have been used. A Neural Network approach has
      been adopted as well. A correlation between the roughness parameters has been
      also supposed in the simulation as a priori information, to evaluate its effect
      on the estimation accuracy. The methods have been tested on simulated data to
      compare their performances as function of number of looks, incidence angles and
      frequency bands, thus identifying the best radar configuration in terms of
      estimation accuracy. Polarimetric measurements acquired during MAC Europe and SIR
      C campaigns, over selected bare soil fields, have been also used as validation
      data.

PMID- 27873983
TI  - Rural Land Use Change during 1986-2002 in Lijiang, China, Based on Remote Sensing
      and GIS Data.
AB  - As a local environmental issue with global importance, land use/land cover change
      (LUCC) has always been one of the key issues in geography and environmental
      studies with the expansion of regional case studies. While most of LUCC studies
      in China have focused on urban land use change, meanwhile, compared with the
      rapid change of urban land use in the coastal areas of eastern China, slow but
      distinct rural land use changes have also occurred in the mountainous areas of
      western China since the late 1980s. In this case through a study in Lijiang
      County of Yunnan Province, with the application of remote sensing data and
      geographic information system techniques, the process of rural land use change in
      mountain areas of western China was monitored through extensive statistical
      analysis of detailed regional data. The results showed significant increases in
      construction land, paddy field and dry land, and a decrease in dense forest land
      and waste grassland between 1986 and 2002. The conversions between dense forest
      land and sparse forest land, grassland, waste grassland and dry land were the
      primary processes of rural land use change. Sparse forest land had the highest
      rate of land use change, with glacier or snow-capped land the lowest; while human
      settlement and rural economic development were found to be the main driving
      forces of regional difference in the integrated land use change rate among the 24
      towns of Lijiang County. Quantified through landscape metrics, spatial patterns
      of rural land use change were represented as an increase in landscape diversity
      and landscape fragmentation, and the regularization of patch shapes, suggesting
      the intensification of human disturbances and degradation of ecological quality
      in the rural landscape.

PMID- 27873984
TI  - A Modified Subpulse SAR Processing Procedure Based on the Range-Doppler Algorithm
      for Synthetic Wideband Waveforms.
AB  - Synthetic wideband waveforms (SWW) combine a stepped frequency CW waveform and a
      chirp signal waveform to achieve high range resolution without requiring a large
      bandwidth or the consequent very high sampling rate. If an efficient algorithm
      like the range-Doppler algorithm (RDA) is used to acquire the SAR images for
      synthetic wideband signals, errors occur due to approximations, so the images may
      not show the best possible result. This paper proposes a modified subpulse SAR
      processing algorithm for synthetic wideband signals which is based on RDA. An
      experiment with an automobile-based SAR system showed that the proposed algorithm
      is quite accurate with a considerable improvement in resolution and quality of
      the obtained SAR image.

PMID- 27873985
TI  - Eliminating the Interference of Oxygen for Sensing Hydrogen Peroxide with the
      Polyaniline Modified Electrode.
AB  - Polyaniline (PANI) has been shown to possess excellent catalytic activity toward
      oxygen reduction, however, this molecule may interfere with the electrochemical
      measurement of other targets when using a polyaniline modified platinum (PANI/Pt)
      electrode. In this study, we have demonstrated the considerable effects of
      dissolved oxygen on the sensing of hydrogen peroxide with the PANI/Pt electrode.
      Accordingly, we proposed a strategy to eliminate the influence of dissolved
      oxygen with oxygen scavengers. Our results indicated that as an oxygen scavenger
      sodium thiosulfate was very effective in the removal of dissolved oxygen from the
      sample solution, and had negligible effect on the quantification of hydrogen
      peroxide when its applied concentration was below 1 mM.

PMID- 27873986
TI  - Objective Error Criterion for Evaluation of Mapping Accuracy Based on Sensor Time
      of-Flight Measurements.
AB  - An objective error criterion is proposed for evaluating the accuracy of maps of
      unknown environments acquired by making range measurements with different sensing
      modalities and processing them with different techniques. The criterion can also
      be used for the assessment of goodness of fit of curves or shapes fitted to map
      points. A demonstrative example from ultrasonic mapping is given based on
      experimentally acquired time-of-flight measurements and compared with a very
      accurate laser map, considered as absolute reference. The results of the proposed
      criterion are compared with the Hausdorff metric and the median error criterion
      results. The error criterion is sufficiently general and flexible that it can be
      applied to discrete point maps acquired with other mapping techniques and sensing
      modalities as well.

PMID- 27873987
TI  - Electrochemical Immunosensor Based on Polythionine/Gold Nanoparticles for the
      Determination of Aflatoxin B1.
AB  - An aflatoxin B1 (AFB1) electrochemical immunosensor was developed by the
      immobilisation of aflatoxin B1-bovine serum albumin (AFB1-BSA) conjugate on a
      polythionine (PTH)/gold nanoparticles (AuNP)-modified glassy carbon electrode
      (GCE). The surface of the AFB1-BSA conjugate was covered with horseradish
      peroxidase (HRP), in order to prevent non-specific binding of the immunosensors
      with ions in the test solution. The AFB1 immunosensor exhibited a quasi
      reversible electrochemistry as indicated by a cyclic voltammetric (CV) peak
      separation (DeltaEp) value of 62 mV. The experimental procedure for the detection
      of AFB1 involved the setting up of a competition between free AFB1 and the
      immobilised AFB1-BSA conjugate for the binding sites of free anti-aflatoxin B1
      (anti-AFB1) antibody. The immunosensor's differential pulse voltammetry (DPV)
      responses (peak currents) decreased as the concentration of free AFB1 increased
      within a dynamic linear range (DLR) of 0.6 - 2.4 ng/mL AFB1 and a limit of
      detection (LOD) of 0.07 ng/mL AFB1. This immunosensing procedure eliminates the
      need for enzyme-labeled secondary antibodies normally used in conventional ELISA
      based immunosensors.

PMID- 27873988
TI  - Comparison of a Resonant Mirror Biosensor (IAsys) and a Quartz Crystal
      Microbalance (QCM) for the Study on Interaction between Paeoniae Radix 801 and
      Endothelin-1.
AB  - A resonant mirror biosensor, IAsys, and a quartz crystal microbalance (QCM) are
      known independently as surface sensitive analytical devices capable of label-free
      and in situ bioassays. In this study, an IAsys and a QCM are employed for a new
      study on the action mechanism of Paeoniae Radix 801 (P. radix 801) by detecting
      the specific interaction between P. radix 801 and endothelin-1 (ET-1). In the
      experiments, ET-1 was immobilized on the surfaces of the IAsys cuvette and the
      QCM substrate by surface modification techniques, and then P. radix 801 solution
      was contacted to the cuvette and the substrate, separately. Then, the binding and
      interaction process between P. radix 801 and ET-1 was monitored by IAsys and QCM,
      respectively. The experimental results showed that P. radix 801 binds ET-1
      specifically. The IAsys and QCM response curves to the ET-1 immobilization and P.
      radix 801 binding are similar in reaction process, but different in binding
      profiles, reflecting different resonation principles. Although both IAsys and QCM
      could detect the interaction of P. radix 801 and ET-1 with high reproducibility
      and reliability through optimization of the ET-1 coating, the reproducibility and
      reliability obtained by IAsys are better than those obtained by QCM, since the
      QCM frequency is more sensitive to temperature fluctuations, atmospheric changes
      and mechanical disturbances. However, IAsys and QCM are generally potent and
      reliable tools to study the interaction of P. radix 801 and ET-1, and can
      conclusively be applied to the action mechanism of P. radix 801.

PMID- 27873989
TI  - Imprinting of Molecular Recognition Sites on Nanostructures and Its Applications
      in Chemosensors.
AB  - Biological receptors including enzymes, antibodies and active proteins have been
      widely used as the detection platform in a variety of chemo/biosensors and
      bioassays. However, the use of artificial host materials in chemical/biological
      detections has become increasingly attractive, because the synthetic recognition
      systems such as molecularly imprinted polymers (MIPs) usually have lower costs,
      higher physical/chemical stability, easier preparation and better engineering
      possibility than biological receptors. Molecular imprinting is one of the most
      efficient strategies to offer a synthetic route to artificial recognition systems
      by a template polymerization technique, and has attracted considerable efforts
      due to its importance in separation, chemo/biosensors, catalysis and biomedicine.
      Despite the fact that MIPs have molecular recognition ability similar to that of
      biological receptors, traditional bulky MIP materials usually exhibit a low
      binding capacity and slow binding kinetics to the target species. Moreover, the
      MIP materials lack the signal-output response to analyte binding events when used
      as recognition elements in chemo/biosensors or bioassays. Recently, various
      explorations have demonstrated that molecular imprinting nanotechniques may
      provide a potential solution to these difficulties. Many successful examples of
      the development of MIP-based sensors have also been reported during the past
      several decades. This review will begin with a brief introduction to the
      principle of molecular imprinting nanotechnology, and then mainly summarize
      various synthesis methodologies and recognition properties of MIP nanomaterials
      and their applications in MIP-based chemosensors. Finally, the future
      perspectives and efforts in MIP nanomaterials and MIP-based sensors are given.

PMID- 27873992
TI  - Nondestructive Characterization by Advanced Synchrotron Light Techniques:
      Spectromicroscopy and Coherent Radiology.
AB  - The advanced characteristics of synchrotron light has led in recent years to the
      development of a series of new experimental techniques to investigate chemical
      and physical properties on a microscopic scale. Although originally developed for
      materials science and biomedical research, such techniques find increasing
      applications in other domains - and could be quite useful for the study and
      conservation of cultural heritage. Specifically, they can nondestructively
      provide detailed chemical composition information that can be useful for the
      identification of specimens, for the discovery of historical links based on the
      sources of chemical raw materials and on chemical processes, for the analysis of
      damage, their causes and remedies and for many other issues. Likewise,
      morphological and structural information on a microscopic scale is useful for the
      identification, study and preservation of many different cultural and historical
      specimens. We concentrate here on two classes of techniques: in the first case,
      photoemission spectromicroscopy. This is the result of the advanced evolution of
      photoemission techniques like ESCA (Electron Microscopy for Chemical Analysis).
      By combining high lateral resolution to spectroscopy, photoemission
      spectromicroscopy can deliver fine chemical information on a microscopic scale in
      a nondestructive fashion. The second class of techniques exploits the high
      lateral coherence of modern synchrotron sources, a byproduct of the quest for
      high brightness or brilliance. We will see that such techniques now push
      radiology into the submicron scale and the submillisecond time domain.
      Furthermore, they can be implemented in a tomographic mode, increasing the
      information and becoming potentially quite useful for the analysis of cultural
      heritage specimens.

PMID- 27873991
TI  - Array Biosensor for Toxin Detection: Continued Advances.
AB  - The following review focuses on progress made in the last five years with the NRL
      Array Biosensor, a portable instrument for rapid and simultaneous detection of
      multiple targets. Since 2003, the Array Biosensor has been automated and
      miniaturized for operation at the point-of-use. The Array Biosensor has also been
      used to demonstrate (1) quantitative immunoassays against an expanded number of
      toxins and toxin indicators in food and clinical fluids, and (2) the efficacy of
      semi-selective molecules as alternative recognition moieties. Blind trials, with
      unknown samples in a variety of matrices, have demonstrated the versatility,
      sensitivity, and reliability of the automated system.

PMID- 27873990
TI  - Na+,K+-ATPase as the Target Enzyme for Organic and Inorganic Compounds.
AB  - This paper gives an overview of the literature data concerning specific and non
      specific inhibitors of Na+,K+-ATPase receptor. The immobilization approaches
      developed to improve the rather low time and temperature stability of Na+,K+
      ATPase, as well to preserve the enzyme properties were overviewed. The functional
      immobilization of Na+,K+-ATPase receptor as the target, with preservation of the
      full functional protein activity and access of various substances to an optimum
      number of binding sites under controlled conditions in the combination with high
      sensitive technology for the detection of enzyme activity is the basis for
      application of this enzyme in medical, pharmaceutical and environmental research.

PMID- 27873993
TI  - Fully-Non-Contact Masking-Based Holography Inspection on Dimensionally Responsive
      Artwork Materials.
AB  - Environmental control in galleries and museums is a necessity and is informed by
      the knowledge of ongoing processes of deterioration which can threaten the
      integrity and stability of artworks. Invisible dimensional changes in many works
      of art occur following environmental fluctuations as materials respond to the
      changes in humidity and temperature. The constant influence of dimensional
      changes usually remains invisible until displacement generates visible
      deterioration and irreversible damage. This paper exploits fully non contact
      coherent interferometry in a sequential masking procedure for visualising and
      studying surface deformation which is the direct effect of dimensional
      alterations induced by humidity changes. Surface deformation during dimensional
      displacements of constituent materials may occur on any artwork within an
      unstable environment. In this context, the presented research study explores the
      diagnostic potential of fully non contact sensors for the direct structural
      assessment of environmental effects as they occur in real time on works of art.
      The method is employed to characterise material responses, complementing and
      improving understanding of material behaviour in unstable environments.

PMID- 27873995
TI  - Conformational Mobility of GOx Coenzyme Complex on Single-Wall Carbon Nanotubes.
AB  - A critical issue in bioelectrochemical applications that use electrodes modified
      by Single Wall Carbon Nanotubes (SWCNTs) is to ensure high activity of the
      catalytic site of an immobilized enzyme protein interacting with nanomaterials.
      Since Flavin Adenine Dinucleotide (FAD), a coenzyme of glucose oxidase (GOx), is
      the active center of the catalytic site, conformation of which could determine
      the activity of enzyme, it is important to understand the dynamic mechanism of
      its conformational mobility while GOx is adsorbed on SWCNTs with multiple
      orientations. However, this dynamic mechanism still remains unclear at the atomic
      level due to the coenzyme being embedded in the apo-GOx and the limitations of
      appropriate experimental methods. In this study, a molecular dynamics (MD)
      simulation was performed to investigate the conformational mobility mechanism of
      the coenzyme. The trajectory and the interaction energy clearly indicate that the
      adsorption of GOx onto SWCNTs plays an important role in the conformational
      mobility of the coenzyme, and its mobility is greatly affected by the
      distribution of water molecules due to it being hydrophobic.

PMID- 27873994
TI  - A Nonoxidative Electrochemical Sensor Based on a Self-Doped Polyaniline/Carbon
      Nanotube Composite for Sensitive and Selective Detection of the Neurotransmitter
      Dopamine: A Review.
AB  - Most of the current techniques for in vivo detection of dopamine exploit the ease
      of oxidation of this compound. The major problem during the detection is the
      presence of a high concentration of ascorbic acid that is oxidized at nearly the
      same potential as dopamine on bare electrodes. Furthermore, the oxidation product
      of dopamine reacts with ascorbic acid present in samples and regenerates dopamine
      again, which severely limits the accuracy of the detection. Meanwhile, the
      product could also form a melanin-like insulating film on the electrode surface,
      which decreases the sensitivity of the electrode. Various surface modifications
      on the electrode, new materials for making the electrodes, and new
      electrochemical techniques have been exploited to solve these problems. Recently
      we developed a new electrochemical detection method that did not rely on direct
      oxidation of dopamine on electrodes, which may naturally solve these problems.
      This approach takes advantage of the high performance of our newly developed
      poly(anilineboronic acid)/carbon nanotube composite and the excellent
      permselectivity of the ion-exchange polymer Nafion. The high affinity binding of
      dopamine to the boronic acid groups of the polymer affects the electrochemical
      properties of the polyaniline backbone, which act as the basis for the
      transduction mechanism of this non-oxidative dopamine sensor. The unique
      reduction capability and high conductivity of single-stranded DNA functionalized
      single-walled carbon nanotubes greatly improved the electrochemical activity of
      the polymer in a physiologically-relevant buffer, and the large surface area of
      the carbon nanotubes increased the density of the boronic acid receptors. The
      high sensitivity and selectivity of the sensor show excellent promise toward
      molecular diagnosis of Parkinson's disease. In this review, we will focus on the
      discussion of this novel detection approach, the new interferences in this
      detection approach, and how to eliminate these interferences toward in vivo and
      in vitro detection of the neurotransmitter dopamine.

PMID- 27873996
TI  - Voltammetric Behaviour of Sulfamethoxazole on Electropolymerized-Molecularly
      Imprinted Overoxidized Polypyrrole.
AB  - In this work, preparation of a molecularly imprinted polymer (MIP) film and its
      recognition properties for sulfamethoxazolewere investigated. The overoxidized
      polypyrrole (OPPy) film was prepared by the cyclic voltammetric deposition of
      pyrrole (Py) in the presence of supporting electrolyte (tetrabutylammonium
      perchlorate-TBAP) with and without a template molecule (sulfamethoxazole) on a
      pencil graphite electrode (PGE). The voltammetric behaviour of sulfamethoxazole
      on imprinted and non-imprinted (NIP) films was investigated by differential pulse
      voltammetry (DPV) in Britton-Robinson (BR) buffer solutions prepared in different
      ratio of acetonitrile-water binary mixture, between the pH 1.5 and 7.0. The
      effect of the acetonitrile-water ratio and pH, monomer and template
      concentrations, electropolymerization cycles on the performance of the MIP
      electrode was investigated and optimized. The MIP electrode exhibited the best
      reproducibility and highest sensitivity. The results showed that changing
      acetonitrile-water ratio and pH of BR buffer solution changes the oxidation peak
      current values. The highest anodic signal of sulfamethoxazole was obtained in BR
      buffer solution prepared in 50% (v/v) acetonitrile-water at pH 2.5. The
      calibration curve for sulfamethoxazole at MIP electrode has linear region for a
      concentration range of 25.10-3 to 0.75 mM (R2=0.9993). The detection limit of
      sulfamethoxazole was found as 3.59.10-4 mM (S/N=3). The same method was also
      applied to determination of sulfamethoxazole in commercial pharmaceutical
      samples. Method precision (RSD87%) were satisfactory. The proposed method is
      simple and quick. The polypyrrole (PPy) electrodes have low response time, good
      mechanical stability and are disposable simple to construct.

PMID- 27873998
TI  - Corrigendum: Sequences flanking the core-binding site modulate glucocorticoid
      receptor structure and activity.

PMID- 27873997
TI  - Estimation of Atmospheric Path Delays in TerraSAR-X Data using Models vs.
      Measurements.
AB  - Spaceborne synthetic aperture radar (SAR) measurements of the Earth's surface
      depend on electromagnetic waves that are subject to atmospheric path delays, in
      turn affecting geolocation accuracy. The atmosphere influences radar signal
      propagation by modifying its velocity and direction, effects which can be
      modeled. We use TerraSAR-X (TSX) data to investigate improvements in the
      knowledge of the scene geometry. To precisely estimate atmospheric path delays,
      we analyse the signal return of four corner reflectors with accurately surveyed
      positions (based on differential GPS), placed at different altitudes yet with
      nearly identical slant ranges to the sensor. The comparison of multiple
      measurements with path delay models under these geometric conditions also makes
      it possible to evaluate the corrections for the atmospheric path delay made by
      the TerraSAR processor and to propose possible improvements.

PMID- 27873999
TI  - Evidence from stable isotopes and 10Be for solar system formation triggered by a
      low-mass supernova.
AB  - About 4.6 billion years ago, some event disturbed a cloud of gas and dust,
      triggering the gravitational collapse that led to the formation of the solar
      system. A core-collapse supernova, whose shock wave is capable of compressing
      such a cloud, is an obvious candidate for the initiating event. This hypothesis
      can be tested because supernovae also produce telltale patterns of short-lived
      radionuclides, which would be preserved today as isotopic anomalies. Previous
      studies of the forensic evidence have been inconclusive, finding a pattern of
      isotopes differing from that produced in conventional supernova models. Here we
      argue that these difficulties either do not arise or are mitigated if the
      initiating supernova was a special type, low in mass and explosion energy. Key to
      our conclusion is the demonstration that short-lived 10Be can be readily
      synthesized in such supernovae by neutrino interactions, while anomalies in
      stable isotopes are suppressed.

PMID- 27874001
TI  - Spray printing of organic semiconducting single crystals.
AB  - Single-crystal semiconductors have been at the forefront of scientific interest
      for more than 70 years, serving as the backbone of electronic devices. Inorganic
      single crystals are typically grown from a melt using time-consuming and energy
      intensive processes. Organic semiconductor single crystals, however, can be grown
      using solution-based methods at room temperature in air, opening up the
      possibility of large-scale production of inexpensive electronics targeting
      applications ranging from field-effect transistors and light-emitting diodes to
      medical X-ray detectors. Here we demonstrate a low-cost, scalable spray-printing
      process to fabricate high-quality organic single crystals, based on various
      semiconducting small molecules on virtually any substrate by combining the
      advantages of antisolvent crystallization and solution shearing. The crystals'
      size, shape and orientation are controlled by the sheer force generated by the
      spray droplets' impact onto the antisolvent's surface. This method demonstrates
      the feasibility of a spray-on single-crystal organic electronics.

PMID- 27874002
TI  - Atomically resolved phase transition of fullerene cations solvated in helium
      droplets.
AB  - Helium has a unique phase diagram and below 25 bar it does not form a solid even
      at the lowest temperatures. Electrostriction leads to the formation of a solid
      layer of helium around charged impurities at much lower pressures in liquid and
      superfluid helium. These so-called 'Atkins snowballs' have been investigated for
      several simple ions. Here we form HenC60+ complexes with n exceeding 100 via
      electron ionization of helium nanodroplets doped with C60. Photofragmentation of
      these complexes is measured by merging a tunable narrow-bandwidth laser beam with
      the ions. A switch from red- to blueshift of the absorption frequency of HenC60+
      on addition of He atoms at n=32 is associated with a phase transition in the
      attached helium layer from solid to partly liquid (melting of the Atkins
      snowball). Elaborate molecular dynamics simulations using a realistic force field
      and including quantum effects support this interpretation.

PMID- 27874000
TI  - Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson
      disease.
AB  - Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in
      mice, and mtDNA damage accumulates in the human brain with aging and
      neurodegenerative disorders such as Parkinson disease (PD). Here, we study the
      complete spectrum of mtDNA changes, including deletions, copy-number variation
      and point mutations, in single neurons from the dopaminergic substantia nigra and
      other brain areas of individuals with Parkinson disease and neurologically
      healthy controls. We show that in dopaminergic substantia nigra neurons of
      healthy individuals, mtDNA copy number increases with age, maintaining the pool
      of wild-type mtDNA population in spite of accumulating deletions. This
      upregulation fails to occur in individuals with Parkinson disease, however,
      resulting in depletion of the wild-type mtDNA population. By contrast, neuronal
      mtDNA point mutational load is not increased in Parkinson disease. Our findings
      suggest that dysregulation of mtDNA homeostasis is a key process in the
      pathogenesis of neuronal loss in Parkinson disease.

PMID- 27874003
TI  - Nanomechanical electro-optical modulator based on atomic heterostructures.
AB  - Two-dimensional atomic heterostructures combined with metallic nanostructures
      allow one to realize strong light-matter interactions. Metallic nanostructures
      possess plasmonic resonances that can be modulated by graphene gating. In
      particular, spectrally narrow plasmon resonances potentially allow for very high
      graphene-enabled modulation depth. However, the modulation depths achieved with
      this approach have so far been low and the modulation wavelength range limited.
      Here we demonstrate a device in which a graphene/hexagonal boron nitride
      heterostructure is suspended over a gold nanostripe array. A gate voltage across
      these devices alters the location of the two-dimensional crystals, creating
      strong optical modulation of its reflection spectra at multiple wavelengths: in
      ultraviolet Fabry-Perot resonances, in visible and near-infrared diffraction
      coupled plasmonic resonances and in the mid-infrared range of hexagonal boron
      nitride's upper Reststrahlen band. Devices can be extremely subwavelength in
      thickness and exhibit compact and truly broadband modulation of optical signals
      using heterostructures of two-dimensional materials.

PMID- 27874004
TI  - Spontaneous formation of structurally diverse membrane channel architectures from
      a single antimicrobial peptide.
AB  - Many antimicrobial peptides (AMPs) selectively target and form pores in microbial
      membranes. However, the mechanisms of membrane targeting, pore formation and
      function remain elusive. Here we report an experimentally guided unbiased
      simulation methodology that yields the mechanism of spontaneous pore assembly for
      the AMP maculatin at atomic resolution. Rather than a single pore, maculatin
      forms an ensemble of structurally diverse temporarily functional low-oligomeric
      pores, which mimic integral membrane protein channels in structure. These pores
      continuously form and dissociate in the membrane. Membrane permeabilization is
      dominated by hexa-, hepta- and octamers, which conduct water, ions and small
      dyes. Pores form by consecutive addition of individual helices to a transmembrane
      helix or helix bundle, in contrast to current poration models. The diversity of
      the pore architectures-formed by a single sequence-may be a key feature in
      preventing bacterial resistance and could explain why sequence-function
      relationships in AMPs remain elusive.

PMID- 27874005
TI  - The Hippo signalling pathway coordinates organ growth and limits developmental
      variability by controlling dilp8 expression.
AB  - Coordination of organ growth during development is required to generate fit
      individuals with fixed proportions. We recently identified Drosophila Dilp8 as a
      key hormone in coupling organ growth with animal maturation. In addition, dilp8
      mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function
      for Dilp8 in ensuring developmental stability. The signals regulating Dilp8
      activity during normal development are not yet known. Here, we show that the
      transcriptional co-activators of the Hippo (Hpo) pathway, Yorkie (Yki, YAP/TAZ)
      and its DNA-binding partner Scalloped (Sd), directly regulate dilp8 expression
      through a Hpo-responsive element (HRE) in the dilp8 promoter. We further
      demonstrate that mutation of the HRE by genome-editing results in animals with
      increased FA, thereby mimicking full dilp8 loss of function. Therefore, our
      results indicate that growth coordination of organs is connected to their growth
      status through a feedback loop involving Hpo and Dilp8 signalling pathways.

PMID- 27874006
TI  - Fission and fusion scenarios for magnetic microswimmer clusters.
AB  - Fission and fusion processes of particle clusters occur in many areas of physics
      and chemistry from subnuclear to astronomic length scales. Here we study fission
      and fusion of magnetic microswimmer clusters as governed by their hydrodynamic
      and dipolar interactions. Rich scenarios are found that depend crucially on
      whether the swimmer is a pusher or a puller. In particular a linear magnetic
      chain of pullers is stable while a pusher chain shows a cascade of fission (or
      disassembly) processes as the self-propulsion velocity is increased. Contrarily,
      magnetic ring clusters show fission for any type of swimmer. Moreover, we find a
      plethora of possible fusion (or assembly) scenarios if a single swimmer collides
      with a ringlike cluster and two rings spontaneously collide. Our predictions are
      obtained by computer simulations and verifiable in experiments on active
      colloidal Janus particles and magnetotactic bacteria.

PMID- 27874007
TI  - Phase transformation strengthening of high-temperature superalloys.
AB  - Decades of research has been focused on improving the high-temperature properties
      of nickel-based superalloys, an essential class of materials used in the hot
      section of jet turbine engines, allowing increased engine efficiency and reduced
      CO2 emissions. Here we introduce a new 'phase-transformation strengthening'
      mechanism that resists high-temperature creep deformation in nickel-based
      superalloys, where specific alloying elements inhibit the deleterious deformation
      mode of nanotwinning at temperatures above 700  degrees C. Ultra-high-resolution
      structure and composition analysis via scanning transmission electron microscopy,
      combined with density functional theory calculations, reveals that a superalloy
      with higher concentrations of the elements titanium, tantalum and niobium
      encourage a shear-induced solid-state transformation from the gamma' to eta phase
      along stacking faults in gamma' precipitates, which would normally be the
      precursors of deformation twins. This nanoscale eta phase creates a low-energy
      structure that inhibits thickening of stacking faults into twins, leading to
      significant improvement in creep properties.

PMID- 27874008
TI  - The GCN5-CITED2-PKA signalling module controls hepatic glucose metabolism through
      a cAMP-induced substrate switch.
AB  - Hepatic gluconeogenesis during fasting results from gluconeogenic gene activation
      via the glucagon-cAMP-protein kinase A (PKA) pathway, a process whose
      dysregulation underlies fasting hyperglycemia in diabetes. Such transcriptional
      activation requires epigenetic changes at promoters by mechanisms that have
      remained unclear. Here we show that GCN5 functions both as a histone
      acetyltransferase (HAT) to activate fasting gluconeogenesis and as an
      acetyltransferase for the transcriptional co-activator PGC-1alpha to inhibit
      gluconeogenesis in the fed state. During fasting, PKA phosphorylates GCN5 in a
      manner dependent on the transcriptional coregulator CITED2, thereby increasing
      its acetyltransferase activity for histone and attenuating that for PGC-1alpha.
      This substrate switch concomitantly promotes both epigenetic changes associated
      with transcriptional activation and PGC-1alpha-mediated coactivation, thereby
      triggering gluconeogenesis. The GCN5-CITED2-PKA signalling module and associated
      GCN5 substrate switch thus serve as a key driver of gluconeogenesis. Disruption
      of this module ameliorates hyperglycemia in obese diabetic animals, offering a
      potential therapeutic strategy for such conditions.

PMID- 27874009
TI  - Corrigendum: Regulation of PERK-eIF2alpha signalling by tuberous sclerosis
      complex-1 controls homoeostasis and survival of myelinating oligodendrocytes.

PMID- 27874010
TI  - Modified relaxation dynamics and coherent energy exchange in coupled vibration
      cavity polaritons.
AB  - Coupling vibrational transitions to resonant optical modes creates vibrational
      polaritons shifted from the uncoupled molecular resonances and provides a
      convenient way to modify the energetics of molecular vibrations. This approach is
      a viable method to explore controlling chemical reactivity. In this work, we
      report pump-probe infrared spectroscopy of the cavity-coupled C-O stretching band
      of W(CO)6 and the direct measurement of the lifetime of a vibration-cavity
      polariton. The upper polariton relaxes 10 times more quickly than the uncoupled
      vibrational mode. Tuning the polariton energy changes the polariton transient
      spectra and relaxation times. We also observe quantum beats, so-called vacuum
      Rabi oscillations, between the upper and lower vibration-cavity polaritons. In
      addition to establishing that coupling to an optical cavity modifies the energy
      transfer dynamics of the coupled molecules, this work points out the possibility
      of systematic and predictive modification of the excited-state kinetics of
      vibration-cavity polariton systems.

PMID- 27874012
TI  - Secondary migration and leakage of methane from a major tight-gas system.
AB  - Tight-gas and shale-gas systems can undergo significant depressurization during
      basin uplift and erosion of overburden due primarily to the natural leakage of
      hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from
      such systems are poorly documented and understood. Here we show, in a study of
      produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas
      system in western Canada, that hydrocarbon fluid loss is focused along distinct
      curvilinear pathways controlled by stratigraphic trends with superior matrix
      permeability and likely also structural trends with enhanced fracture
      permeability. Natural gas along these pathways is preferentially enriched in
      methane because of selective secondary migration and phase separation processes.
      The leakage and secondary migration of thermogenic methane to surficial strata is
      part of an ongoing carbon cycle in which organic carbon in the deep sedimentary
      basin transforms into methane, and ultimately reaches the near-surface
      groundwater and atmosphere.

PMID- 27874011
TI  - Inhibition of glycine transporter-1 in the dorsal vagal complex improves
      metabolic homeostasis in diabetes and obesity.
AB  - Impaired glucose homeostasis and energy balance are integral to the
      pathophysiology of diabetes and obesity. Here we show that administration of a
      glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the
      dorsal vagal complex (DVC) suppresses glucose production, increases glucose
      tolerance and reduces food intake and body weight gain in healthy, obese and
      diabetic rats. These findings provide proof of concept that GlyT1 inhibition in
      the brain improves glucose and energy homeostasis. Considering the clinical
      safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical
      trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to
      be repurposed as a treatment of both obesity and diabetes.

PMID- 27874014
TI  - Epithelial extracellular ATP: an initiator of immunity to parasitic infections.

PMID- 27874013
TI  - Crystal structure of FabZ-ACP complex reveals a dynamic seesaw-like catalytic
      mechanism of dehydratase in fatty acid biosynthesis.
AB  - Fatty acid biosynthesis (FAS) is a vital process in cells. Fatty acids are
      essential for cell assembly and cellular metabolism. Abnormal FAS directly
      correlates with cell growth delay and human diseases, such as metabolic syndromes
      and various cancers. The FAS system utilizes an acyl carrier protein (ACP) as a
      transporter to stabilize and shuttle the growing fatty acid chain throughout
      enzymatic modules for stepwise catalysis. Studying the interactions between
      enzymatic modules and ACP is, therefore, critical for understanding the
      biological function of the FAS system. However, the information remains unclear
      due to the high flexibility of ACP and its weak interaction with enzymatic
      modules. We present here a 2.55 A crystal structure of type II FAS dehydratase
      FabZ in complex with holo-ACP, which exhibits a highly symmetrical FabZ hexamer
      ACP3 stoichiometry with each ACP binding to a FabZ dimer subunit. Further
      structural analysis, together with biophysical and computational results, reveals
      a novel dynamic seesaw-like ACP binding and catalysis mechanism for the
      dehydratase module in the FAS system, which is regulated by a critical gatekeeper
      residue (Tyr100 in FabZ) that manipulates the movements of the beta-sheet layer.
      These findings improve the general understanding of the dehydration process in
      the FAS system and will potentially facilitate drug and therapeutic design for
      diseases associated with abnormalities in FAS.

PMID- 27874017
TI  - Corrigendum: Determination of Arabidopsis thaliana telomere length by PCR.

PMID- 27874016
TI  - Mitochondrial growth during the cell cycle of Trypanosoma brucei bloodstream
      forms.
AB  - Mitochondrial organelles need to be replicated during cell division. Many aspects
      of this process have been studied in great detail, however the actual size
      increase and the position of organelle growth are less well understood. We use
      the protozoan parasite Trypanosoma brucei that contains a single mitochondrion to
      study organelle biogenesis by fluorescence microscopy. From the analysis of more
      than 1000 T. brucei bloodstream form cells of a nonsynchronous population we
      conclude that the mitochondrial network mostly grows from two areas along the
      main organelle axis, posterior and anterior of the nucleus. Loops and branches
      from these two areas eventually fuse to build a complex network. Together with
      the appearance of the division fold in the posterior part of the cell, pruning of
      the mitochondrial network and finally separation into the two daughter cells
      occurs. Overall organelle biogenesis is not continuous during cell growth and
      occurs mostly in the last part of the cell cycle. Furthermore, using 3D STED
      super resolution microscopy we reconstruct the volume of the organelle and
      characterize the region where the mitochondrial genome is positioned by serial
      block face scanning electron microscopy.

PMID- 27874015
TI  - Metabolic sialic acid blockade lowers the activation threshold of moDCs for TLR
      stimulation.
AB  - Sialic acid sugars cover the surface of dendritic cells (DCs) and have been
      suggested to impact several aspects of DC biology. Research into the role of
      sialic acids in DCs, however, is complicated by the limited number of tools
      available to modulate sialic acid expression. Here we report on a synthetic,
      fluorinated sialic acid mimetic, Ac53FaxNeu5Ac, which potently blocks sialic acid
      expression in human monocyte-derived DCs (moDCs). Sialic acid blockade enhanced
      the responsiveness of moDCs to Toll-like receptor (TLR) stimulation as measured
      by increased maturation marker expression and cytokine production. Consequently,
      the T-cell activation capacity of Ac53FaxNeu5Ac-treated moDCs was strongly
      increased. In addition to sialic acids, moDCs also expressed the sialic acid
      binding immunoglobulin-like lectins (Siglecs) -3, -5, -7, -9 and -10, immune
      inhibitory receptors recognizing these sialic acids. Treatment with Ac53FaxNeu5Ac
      abrogated putative cis and trans interactions between sialic acids and Siglec-7/
      9. Together, these data indicate that sialic acids limit the activation of moDCs
      via the TLR pathway, potentially by interacting with Siglec-7 or Siglec-9.
      Metabolic sialic acid blockade with Ac53FaxNeu5Ac could therefore potentially be
      used to generate more potent DC-based vaccines for induction of robust anti-viral
      or anti-tumor immune responses.

PMID- 27874018
TI  - Three-dimensional label-free imaging and quantification of lipid droplets in live
      hepatocytes.
AB  - Lipid droplets (LDs) are subcellular organelles with important roles in lipid
      storage and metabolism and involved in various diseases including cancer,
      obesity, and diabetes. Conventional methods, however, have limited ability to
      provide quantitative information on individual LDs and have limited capability
      for three-dimensional (3-D) imaging of LDs in live cells especially for fast
      acquisition of 3-D dynamics. Here, we present an optical method based on 3-D
      quantitative phase imaging to measure the 3-D structural distribution and
      biochemical parameters (concentration and dry mass) of individual LDs in live
      cells without using exogenous labelling agents. The biochemical change of LDs
      under oleic acid treatment was quantitatively investigated, and 4-D tracking of
      the fast dynamics of LDs revealed the intracellular transport of LDs in live
      cells.

PMID- 27874021
TI  - Erratum: Symmetry Breaking by Surface Blocking: Synthesis of Bimorphic Silver
      Nanoparticles, Nanoscale Fishes and Apples.

PMID- 27874019
TI  - Long-range synchrony and emergence of neural reentry.
AB  - Neural synchronization across long distances is a functionally important
      phenomenon in health and disease. In order to access the basis of different modes
      of long-range synchrony, we monitor spiking activities over centimetre scale in
      cortical networks and show that the mode of synchrony depends upon a length
      scale, lambda, which is the minimal path that activity should propagate through
      to find its point of origin ready for reactivation. When lambda is larger than
      the physical dimension of the network, distant neuronal populations operate
      synchronously, giving rise to irregularly occurring network-wide events that last
      hundreds of milliseconds to several seconds. In contrast, when lambda approaches
      the dimension of the network, a continuous self-sustained reentry propagation
      emerges, a regular seizure-like mode that is marked by precise spatiotemporal
      patterns ('synfire chains') and may last many minutes. Termination of a reentry
      phase is preceded by a decrease of propagation speed to a halt. Stimulation
      decreases both propagation speed and lambda values, which modifies the synchrony
      mode respectively. The results contribute to the understanding of the origin and
      termination of different modes of neural synchrony as well as their long-range
      spatial patterns, while hopefully catering to manipulation of the phenomena in
      pathological conditions.

PMID- 27874020
TI  - Friedelin Synthase from Maytenus ilicifolia: Leucine 482 Plays an Essential Role
      in the Production of the Most Rearranged Pentacyclic Triterpene.
AB  - Among the biologically active triterpenes, friedelin has the most-rearranged
      structure produced by the oxidosqualene cyclases and is the only one containing a
      cetonic group. In this study, we cloned and functionally characterized friedelin
      synthase and one cycloartenol synthase from Maytenus ilicifolia (Celastraceae).
      The complete coding sequences of these 2 genes were cloned from leaf mRNA, and
      their functions were characterized by heterologous expression in yeast. The
      cycloartenol synthase sequence is very similar to other known OSCs of this type
      (approximately 80% identity), although the M. ilicifolia friedelin synthase amino
      acid sequence is more related to beta-amyrin synthases (65-74% identity), which
      is similar to the friedelin synthase cloned from Kalanchoe daigremontiana.
      Multiple sequence alignments demonstrated the presence of a leucine residue two
      positions upstream of the friedelin synthase Asp-Cys-Thr-Ala-Glu (DCTAE) active
      site motif, while the vast majority of OSCs identified so far have a valine or
      isoleucine residue at the same position. The substitution of the leucine residue
      with valine, threonine or isoleucine in M. ilicifolia friedelin synthase
      interfered with substrate recognition and lead to the production of different
      pentacyclic triterpenes. Hence, our data indicate a key role for the leucine
      residue in the structure and function of this oxidosqualene cyclase.

PMID- 27874022
TI  - In-depth comparison of somatic point mutation callers based on different tumor
      next-generation sequencing depth data.
AB  - Four popular somatic single nucleotide variant (SNV) calling methods (Varscan,
      SomaticSniper, Strelka and MuTect2) were carefully evaluated on the real whole
      exome sequencing (WES, depth of ~50X) and ultra-deep targeted sequencing (UDT
      Seq, depth of ~370X) data. The four tools returned poor consensus on candidates
      (only 20% of calls were with multiple hits by the callers). For both WES and UDT
      Seq, MuTect2 and Strelka obtained the largest proportion of COSMIC entries as
      well as the lowest rate of dbSNP presence and high-alternative-alleles-in-control
      calls, demonstrating their superior sensitivity and accuracy. Combining different
      callers does increase reliability of candidates, but narrows the list down to
      very limited range of tumor read depth and variant allele frequency. Calling SNV
      on UDT-Seq data, which were of much higher read-depth, discovered additional true
      positive variations, despite an even more tremendous growth in false positive
      predictions. Our findings not only provide valuable benchmark for state-of-the
      art SNV calling methods, but also shed light on the access to more accurate SNV
      identification in the future.

PMID- 27874024
TI  - Exploring Spatio-temporal Dynamics of Cellular Automata for Pattern Recognition
      in Networks.
AB  - Network science is an interdisciplinary field which provides an integrative
      approach for the study of complex systems. In recent years, network modeling has
      been used for the study of emergent phenomena in many real-world applications.
      Pattern recognition in networks has been drawing attention to the importance of
      network characterization, which may lead to understanding the topological
      properties that are related to the network model. In this paper, the Life-Like
      Network Automata (LLNA) method is introduced, which was designed for pattern
      recognition in networks. LLNA uses the network topology as a tessellation of
      Cellular Automata (CA), whose dynamics produces a spatio-temporal pattern used to
      extract the feature vector for network characterization. The method was evaluated
      using synthetic and real-world networks. In the latter, three pattern recognition
      applications were used: (i) identifying organisms from distinct domains of life
      through their metabolic networks, (ii) identifying online social networks and
      (iii) classifying stomata distribution patterns varying according to different
      lighting conditions. LLNA was compared to structural measurements and surpasses
      them in real-world applications, achieving improvement in the classification rate
      as high as 23%, 4% and 7% respectively. Therefore, the proposed method is a good
      choice for pattern recognition applications using networks and demonstrates
      potential for general applicability.

PMID- 27874023
TI  - Methylphenidate and Memory and Attention Adaptation Training for Persistent
      Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled
      Trial.
AB  - The purpose of this multicenter, prospective, randomized, placebo-controlled
      study was to evaluate and compare the efficacy of two cognitive rehabilitation
      interventions (Memory and Attention Adaptation Training (MAAT) and Attention
      Builders Training (ABT)), with and without pharmacological enhancement (ie, with
      methylphenidate (MPH) or placebo), for treating persistent cognitive problems
      after traumatic brain injury (TBI). Adults with a history of TBI at least 4
      months before study enrollment with either objective cognitive deficits or
      subjective cognitive complaints were randomized to receive MPH or placebo and
      MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH
      (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted
      pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome
      measures included scores on neuropsychological measures and subjective rating
      scales. Statistical analyses used linear regression models to predict post
      treatment scores for each outcome variable by treatment type, adjusting for
      relevant covariates. Statistically significant (P<0.05) treatment-related
      improvements in cognitive functioning were found for word-list learning
      (MAAT/placebo>ABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and
      MAAT/MPH>ABT/MPH), and auditory working memory and divided attention
      (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with
      metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects
      of attention, episodic and working memory, and executive functioning after TBI.

PMID- 27874025
TI  - Beyond Antibodies: Development of a Novel Protein Scaffold Based on Human
      Chaperonin 10.
AB  - Human Chaperonin 10 (hCpn10) was utilised as a novel scaffold for presenting
      peptides of therapeutic and diagnostic significance. Molecular dynamic
      simulations and protein sizing analyses identified a peptide linker (P1) optimal
      for the formation of the quarternary hCpn10 heptamer structure. hCpn10 scaffold
      displaying peptides targeting Factor VIIa (CE76-P1) and CD44 (CP7) were expressed
      in E. coli. Functional studies of CE76-P1 indicated nanomolar affinity for Factor
      VIIa (3 nM) similar to the E-76 peptide (6 nM), with undetectable binding to
      Factor X. CE76-P1 was a potent inhibitor of FX activity (via inhibition of Factor
      VIIa) and prolonged clot formation 4 times longer than achieved by E-76 peptide
      as determined by prothrombin time (PT) assays. This improvement in clotting
      function by CE76-P1, highlights the advantages of a heptamer-based scaffold for
      improving avidity by multiple peptide presentation. In another example of hCPn10
      utility as a scaffold, CP7 bound to native CD44 overexpressed on cancer cells and
      bound rCD44 with high affinity (KD 9.6 nM). The ability to present various
      peptides through substitution of the hCpn10 mobile loop demonstrates its utility
      as a novel protein scaffold.

PMID- 27874026
TI  - Bandgap tuning of mixed organic cation utilizing chemical vapor deposition
      process.
AB  - Bandgap tuning of a mixed organic cation perovskite is demonstrated via chemical
      vapor deposition process. The optical and electrical properties of the mixed
      organic cation perovskite can be manipulated by varying the growth time. A slight
      shift of the absorption band to shorter wavelengths is demonstrated with
      increasing growth time, which results in the increment of the current density.
      Hence, based on the optimized growth time, our device exhibits an efficiency of
      15.86% with negligible current hysteresis.

PMID- 27874027
TI  - Circulating long-non coding RNAs as biomarkers of left ventricular diastolic
      function and remodelling in patients with well-controlled type 2 diabetes.
AB  - Contractile dysfunction is underdiagnosed in early stages of diabetic
      cardiomyopathy. We evaluated the potential of circulating long non-coding RNAs
      (lncRNAs) as biomarkers of subclinical cardiac abnormalities in type 2 diabetes.
      Forty-eight men with well-controlled type 2 diabetes and 12 healthy age-matched
      volunteers were enrolled in the study. Left ventricular (LV) parameters were
      measured by magnetic resonance imaging. A panel of lncRNAs was quantified in
      serum by RT-qPCR. No differences in expression levels of lncRNAs were observed
      between type 2 diabetes patients and healthy volunteers. In patients with type 2
      diabetes, long intergenic non-coding RNA predicting cardiac remodeling (LIPCAR)
      was inversely associated with diastolic function, measured as E/A peak flow (P <
      0.050 for all linear models). LIPCAR was positively associated with grade I
      diastolic dysfunction (P < 0.050 for all logistic models). Myocardial infarction
      associated transcript (MIAT) and smooth muscle and endothelial cell-enriched
      migration/differentiation-associated long noncoding RNA (SENCR) were directly
      associated with LV mass to LV end-diastolic volume ratio, a marker of cardiac
      remodelling (P < 0.050 for all linear models). These findings were validated in a
      sample of 30 patients with well-controlled type 2 diabetes. LncRNAs are
      independent predictors of diastolic function and remodelling in patients with
      type 2 diabetes.

PMID- 27874028
TI  - A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary
      delivered immunoblocking of BMP9 and BMP10.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening
      genetic vascular disorder caused by loss-of-function mutations in the genes
      encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4, and bone
      morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10
      blocking antibodies lead to HHT-like vascular defects in the postnatal retinal
      angiogenesis model. Mothers and their newborns share the same immunity through
      the transfer of maternal antibodies during lactation. Here, we investigated
      whether the transmammary delivery route could improve the ease and consistency of
      administering anti-BMP9/10 antibodies in the postnatal retinal angiogenesis
      model. We found that anti-BMP9/10 antibodies, when intraperitoneally injected
      into lactating dams, are efficiently transferred into the blood circulation of
      lactationally-exposed neonatal pups. Strikingly, pups receiving anti-BMP9/10
      antibodies via lactation displayed consistent and robust vascular pathology in
      the retina, which included hypervascularization and defects in arteriovenous
      specification, as well as the presence of multiple and massive arteriovenous
      malformations. Furthermore, RNA-Seq analyses of neonatal retinas identified an
      increase in the key pro-angiogenic factor, angiopoietin-2, as the most
      significant change in gene expression triggered by the transmammary delivery of
      anti-BMP9/10 antibodies. Transmammary-delivered BMP9/10 immunoblocking in the
      mouse neonatal retina is therefore a practical, noninvasive, reliable, and robust
      model of HHT vascular pathology.

PMID- 27874029
TI  - An anti-TNF-alpha antibody mimetic to treat ocular inflammation.
AB  - Infliximab is an antibody that neutralizes TNF-alpha and is used principally by
      systemic administration to treat many inflammatory disorders. We prepared the
      antibody mimetic Fab-PEG-Fab (FpFinfliximab) for direct intravitreal injection to
      assess whether such formulations have biological activity and potential utility
      for ocular use. FpFinfliximab was designed to address side effects caused by
      antibody degradation and the presence of the Fc region. Surface plasmon resonance
      analysis indicated that infliximab and FpFinfliximab maintained binding affinity
      for both human and murine recombinant TNF-alpha. No Fc mediated RPE cellular
      uptake was observed for FpFinfliximab. Both Infliximab and FpFinfliximab
      suppressed ocular inflammation by reducing the number of CD45+ infiltrate cells
      in the EAU mice after a single intravitreal injection at the onset of peak
      disease. These results offer an opportunity to develop and formulate for ocular
      use, FpF molecules designed for single and potentially multiple targets using bi
      specific FpFs.

PMID- 27874030
TI  - Ultrasonic spray coating polymer and small molecular organic film for organic
      light-emitting devices.
AB  - Ultrasonic spray coating process (USCP) with high material -utilization, low
      manufacture costs and compatibility to streamline production has been attractive
      in researches on photoelectric devices. However, surface tension exists in the
      solvent is still a huge obstacle to realize smooth organic film for organic light
      emitting devices (OLEDs) by USCP. Here, high quality polymer anode buffer layer
      and small molecular emitting layer are successfully realized through USCP by
      introducing extra-low surface tension diluent and surface tension control method.
      The introduction of low surface tension methyl alcohol is beneficial to the
      formation of poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)
      films and brings obvious phase separation and improved conductivity to PEDOT:PSS
      film. Besides, a surface tension control method, in which new stable tension
      equilibrium is built at the border of wetting layer, is proposed to eliminate the
      effect of surface tension during the solvent evaporation stage of ultrasonic
      spray coating the film consists of 9,9-Spirobifluoren-2-yl-diphenyl-phosphine
      oxide doped with 10 wt% tris [2-(p -tolyl) pyridine] iridium (III). A smooth and
      homogenous small molecular emitting layer without wrinkles is successfully
      realized. The effectiveness of the ultrasonic spray coating polymer anode buffer
      layer and small molecular emitting layer are also proved by introducing them in
      OLEDs.

PMID- 27874031
TI  - Harnessing short poly(A)-binding protein-interacting peptides for the suppression
      of nonsense-mediated mRNA decay.
AB  - Nonsense-mediated mRNA decay (NMD) is a cellular process that eliminates
      messenger RNA (mRNA) substrates with premature translation termination codons
      (PTCs). In addition, NMD regulates the expression of a number of physiological
      mRNAs, for example transcripts containing long 3' UTRs. Current models implicate
      the interaction between cytoplasmic poly(A)-binding protein (PABPC1) and
      translation termination in NMD. Accordingly, PABPC1 present within close
      proximity of a termination codon antagonizes NMD. Here, we use reporter mRNAs
      with different NMD-inducing 3' UTRs to establish a general NMD-inhibiting
      property of PABPC1. NMD-inhibition is not limited to PABPC1, but can also be
      achieved by peptides consisting of the PABP-interacting motif 2 (PAM2) of
      different proteins when recruited to an NMD-inhibiting position of NMD reporter
      transcripts. The short PAM2 peptides efficiently suppress NMD activated by a long
      3' UTR, an exon-junction complex (EJC) and individual EJC components, and
      stabilize a PTC-containing beta-globin mRNA. In conclusion, our results establish
      short PABPC1-recruiting peptides as potent but position-dependent inhibitors of
      mammalian NMD.

PMID- 27874033
TI  - Influence of combined fundamental potentials in a nonlinear vibration energy
      harvester.
AB  - Ambient mechanical vibrations have emerged as a viable energy source for low
      power wireless sensor nodes aiming the upcoming era of the 'Internet of Things'.
      Recently, purposefully induced dynamical nonlinearities have been exploited to
      widen the frequency spectrum of vibration energy harvesters. Here we investigate
      some critical inconsistencies between the theoretical formulation and
      applications of the bistable Duffing nonlinearity in vibration energy harvesting.
      A novel nonlinear vibration energy harvesting device with the capability to
      switch amidst individually tunable bistable-quadratic, monostable-quartic and
      bistable-quartic potentials has been designed and characterized. Our study
      highlights the fundamentally different large deflection behaviors of the
      theoretical bistable-quartic Duffing oscillator and the experimentally adapted
      bistable-quadratic systems, and underlines their implications in the respective
      spectral responses. The results suggest enhanced performance in the bistable
      quartic potential in comparison to others, primarily due to lower potential
      barrier and higher restoring forces facilitating large amplitude inter-well
      motion at relatively lower accelerations.

PMID- 27874032
TI  - Connexin 32-mediated cell-cell communication is essential for hepatic
      differentiation from human embryonic stem cells.
AB  - Gap junction-mediated cell-cell interactions are highly conserved and play
      essential roles in cell survival, proliferation, differentiation and patterning.
      We report that Connexin 32 (Cx32)-mediated gap junctional intercellular
      communication (GJIC) is necessary for human embryonic stem cell-derived
      hepatocytes (hESC-Heps) during step-wise hepatic lineage restriction and
      maturation. Vitamin K2, previously shown to promote Cx32 expression in mature
      hepatocytes, up-regulated Cx32 expression and GJIC activation during hepatic
      differentiation and maturation, resulting in significant increases of hepatic
      markers expression and hepatocyte functions. In contrast, negative Cx32 regulator
      2-aminoethoxydiphenyl borate blocked hESC-to-hepatocyte maturation and muted
      hepatocyte functions through disruption of GJIC activities. Dynamic gap junction
      organization and internalization are phosphorylation-dependent and the p38
      mitogen-activated protein kinases pathway (MAPK) can negatively regulate Cxs
      through phosphorylation-dependent degradation of Cxs. We found that p38 MAPK
      inhibitor SB203580 improved maturation of hESC-Heps correlating with up
      regulation of Cx32; by contrast, the p38 MAPK activator, anisomycin, blocked hESC
      Heps maturation correlating with down-regulation of Cx32. These results suggested
      that Cx32 is essential for cell-cell interactions that facilitate driving hESCs
      through hepatic-lineage maturation. Regulators of both Cx32 and other members of
      its pathways maybe used as a promising approach on regulating hepatic lineage
      restriction of pluripotent stem cells and optimizing their functional maturation.

PMID- 27874034
TI  - Screening on binary Ti alloy with excellent mechanical property and castability
      for dental prosthesis application.
AB  - In the present study, the microstructure, mechanical property, castability,
      corrosion behavior and in vitro cytocompatibility of binary Ti-2X alloys with
      various alloying elements, including Ag, Bi, Ga, Ge, Hf, In, Mo, Nb, Sn and Zr,
      were systematically investigated, in order to assess their potential applications
      in dental field. The experimental results showed that all binary Ti-2X alloys
      consisted entirely alpha-Ti phase. The tensile strength and microhardness of Ti
      were improved by adding alloying elements. The castability of Ti was
      significantly improved by separately adding 2 wt.% Bi, Ga, Hf, Mo, Nb, Sn and Zr.
      The corrosion resistance of Ti in both normal artificial saliva solution (AS) and
      extreme artificial saliva solution (ASFL, AS with 0.2 wt.% NaF and 0.3 wt.%
      lactic acid) has been improved by separately adding alloying elements. In
      addition, the extracts of studied Ti-2X alloys produced no significant
      deleterious effect to both fibroblasts L929 cells and osteoblast-like MG63 cells,
      indicating a good in vitro cytocompatibility, at the same level as pure Ti. The
      combination of enhanced mechanical properties, castability, corrosion behavior,
      and in vitro cytocompatibility make the developed Ti-2X alloys have great
      potential for future stomatological applications.

PMID- 27874035
TI  - p53 isoform Delta133p53 promotes efficiency of induced pluripotent stem cells and
      ensures genomic integrity during reprogramming.
AB  - Human induced pluripotent stem (iPS) cells have great potential in regenerative
      medicine, but this depends on the integrity of their genomes. iPS cells have been
      found to contain a large number of de novo genetic alterations due to DNA damage
      response during reprogramming. Thus, to maintain the genetic stability of iPS
      cells is an important goal in iPS cell technology. DNA damage response can
      trigger tumor suppressor p53 activation, which ensures genome integrity of
      reprogramming cells by inducing apoptosis and senescence. p53 isoform Delta133p53
      is a p53 target gene and functions to not only antagonize p53 mediated apoptosis,
      but also promote DNA double-strand break (DSB) repair. Here we report that
      Delta133p53 is induced in reprogramming. Knockdown of Delta133p53 results 2-fold
      decrease in reprogramming efficiency, 4-fold increase in chromosomal aberrations,
      whereas overexpression of Delta133p53 with 4 Yamanaka factors showes 4-fold
      increase in reprogamming efficiency and 2-fold decrease in chromosomal
      aberrations, compared to those in iPS cells induced only with 4 Yamanaka factors.
      Overexpression of Delta133p53 can inhibit cell apoptosis and promote DNA DSB
      repair foci formation during reprogramming. Our finding demonstrates that the
      overexpression of Delta133p53 not only enhances reprogramming efficiency, but
      also results better genetic quality in iPS cells.

PMID- 27874036
TI  - Natural zwitterionic betaine enables cells to survive ultrarapid
      cryopreservation.
AB  - Cryoprotectants (CPAs) play a critical role in cryopreservation because they can
      resist the cell damage caused by the freezing process. Current state-of-the-art
      CPAs are mainly based on an organic solvent dimethyl sulfoxide (DMSO), and
      several DMSO-cryopreserved cell products have been brought to market. However,
      the intrinsic toxicity and complex freezing protocol of DMSO still remain as the
      bottleneck of the wide use for clinical applications. Herein, we reported that
      betaine, a natural zwitterionic molecule, could serve as a nontoxic and high
      efficient CPA. At optimum concentration of betaine, different cell types
      exhibited exceptional post-thaw survival efficiency with ultrarapid freezing
      protocol, which was straightforward, cost efficient but difficult to succeed
      using DMSO. Moreover, betaine showed negligible cytotoxicity even after long-term
      exposure of cells. Mechanistically, we hypothesized that betaine could be ultra
      rapidly taken up by cells for intracellular protection during the freezing
      process. This technology unlocks the possibility of alternating the traditional
      toxic CPAs and is applicable to a variety of clinical applications.

PMID- 27874037
TI  - Visualizing epithelial expression of EGFR in vivo with distal scanning side
      viewing confocal endomicroscope.
AB  - Confocal endomicroscopy is an emerging imaging technology that has recently been
      introduced into the clinic to instantaneously collect "optical biopsies" in vivo
      with histology-like quality. Here, we demonstrate a fast scanner located in the
      distal end of a side-viewing instrument using a compact lens assembly with
      numerical aperture of 0.5 to achieve a working distance of 100 MUm and field-of
      view of 300 * 400 MUm2. The microelectromechanical systems (MEMS) mirror was
      designed based on the principle of parametric resonance and images at 5 frames
      per second. The instrument has a 4.2 mm outer diameter and 3 cm rigid length, and
      can pass through the biopsy channel of a medical endoscope. We achieved real time
      optical sections of NIR fluorescence with 0.87 MUm lateral resolution, and were
      able to visualize in vivo binding of a Cy5.5-labeled peptide specific for EGFR to
      the cell surface of pre-cancerous colonocytes within the epithelium of dysplastic
      crypts in mouse colon. By performing targeted imaging with endomicroscopy, we can
      visualize molecular expression patterns in vivo that provide a biological basis
      for disease detection.

PMID- 27874038
TI  - Neural mechanisms underlying touch-induced visual perceptual suppression: An fMRI
      study.
AB  - Crossmodal studies have demonstrated inhibitory as well as facilitatory neural
      effects in higher sensory association and primary sensory cortices. A recent
      human behavioral study reported touch-induced visual perceptual suppression
      (TIVS). Here, we introduced an experimental setting in which TIVS could occur and
      investigated brain activities underlying visuo-tactile interactions using a
      functional magnetic resonance imaging technique. While the suppressive effect of
      touch on vision was only found for half of the participants who could maintain
      their baseline performance above chance level (i.e. TIVS was not well replicated
      here), we focused on individual differences in the effect of touch on vision.
      This effect could be suppressive or enhancement, and the neuronal basis of these
      differences was analyzed. We found larger inhibitory responses in the anterior
      part of the right visual cortex (V1, V2) with higher TIVS magnitude when visuo
      tactile stimuli were presented as spatially congruent. Activations in the right
      anterior superior temporal region, including the secondary somatosensory cortical
      area, were more strongly related to those in the visual cortex (V1, V2) with
      higher TIVS magnitude. These results indicate that inhibitory neural modulations
      from somatosensory to visual cortices and the resulting inhibitory neural
      responses in the visual cortex could be involved in TIVS.

PMID- 27874039
TI  - Effects of light-emitting diode irradiation on the osteogenesis of human
      umbilical cord mesenchymal stem cells in vitro.
AB  - The aim of this study was to examine the effects of light-emitting diode (LED)
      photobiomodulation therapy on the proliferation and differentiation of human
      umbilical cord mesenchymal stem cells (hUMSCs) cultured in osteogenic
      differentiation medium. HUMSCs were irradiated with an LED light at 620 nm and 2
      J/cm2 and monitored for cell proliferation and osteogenic differentiation
      activity. The experiment involved four groups of cells: the control group; the
      osteogenic group (osteo group); the LED group; the osteogenic + LED group (LED +
      osteo group). HUMSC proliferation was detected by performing a3-(4,5
      dimethylthiazol-2yl)-2,5 diphenyltetrazolium bromide(MTT) assay. Osteogenic
      activity was evaluated by performing alkaline phosphatase (ALP) and Von Kossa
      staining, and osteopontin (OPN) gene mRNA expression was evaluated byreverse
      transcription polymerase chain reaction (RT-PCR). The hUMSCs in the LED + osteo
      group exhibited a significantly higher proliferation rate than the other
      subgroups. Additionally, there were greater numbers of ALP-positive cells and Von
      Kossa nodules in the LED + osteo group. OPN mRNA expression in the LED + osteo
      group was higher than other subgroups. In conclusion, low levels of LED light at
      a wavelength of 620 nm enhance the proliferation and osteogenic differentiation
      of hUMSCs during a long culture period.

PMID- 27874040
TI  - Role of valence changes and nanoscale atomic displacements in BiS2-based
      superconductors.
AB  - Superconductivity within layered crystal structures has attracted sustained
      interest among condensed matter community, primarily due to their exotic
      superconducting properties. EuBiS2F is a newly discovered member in the BiS2
      based superconducting family, which shows superconductivity at 0.3 K without
      extrinsic doping. With 50 at.% Ce substitution for Eu, superconductivity is
      enhanced with Tc increased up to 2.2 K. However, the mechanisms for the Tc
      enhancement have not yet been elucidated. In this study, the Ce-doping effect on
      the self-electron-doped superconductor EuBiS2F was investigated by X-ray
      absorption spectroscopy (XAS). We have established a relationship between Ce
      doping and the Tc enhancement in terms of Eu valence changes and nanoscale atomic
      displacements. The new finding sheds light on the interplay among
      superconductivity, charge and local structure in BiS2-based superconductors.

PMID- 27874041
TI  - Surface studies of solids using integral X-ray-induced photoemission yield.
AB  - X-ray induced photoemission yield contains structural information complementary
      to that provided by X-ray Fresnel reflectivity, which presents an advantage to a
      wide variety of surface studies if this information is made easily accessible.
      Photoemission in materials research is commonly acknowledged as a method with a
      probing depth limited by the escape depth of the photoelectrons. Here we show
      that the integral hard-X-ray-induced photoemission yield is modulated by the
      Fresnel reflectivity of a multilayer structure and carries structural information
      that extends well beyond the photoelectron escape depth. A simple electric self
      detection of the integral photoemission yield and Fourier data analysis permit
      extraction of thicknesses of individual layers. The approach does not require
      detection of the reflected radiation and can be considered as a framework for non
      invasive evaluation of buried layers with hard X-rays under grazing incidence.

PMID- 27874042
TI  - Electrical Stimulus Controlled Binding/Unbinding of Human Thrombin-Aptamer
      Complex.
AB  - The binding/unbinding of the human thrombin and its 15-mer single stranded DNA
      aptamer, under the application of external stimulus in the form of electrostatic
      potential/electric field, is investigated by a combination of continuum analysis
      and atomistic molecular dynamics simulation. In agreement with the experiments
      that demonstrate the influence of electrostatic potential on the thrombin/aptamer
      complex, our computations show that the application of positive electric field
      successfully unbinds the thrombin from the aptamer. Results from umbrella
      sampling simulations reveal that there is a decrease in the free energy of
      binding between the thrombin and aptamer in presence of positive electric fields.
      Hydrogen bonding and non-bonded interaction energies, and hence the free energy
      of binding, between the thrombin and its aptamer reduce as the applied electric
      field is shifted from negative to positive values. Our analyses demonstrate that
      application of electrical stimulus modifies the molecular interactions within the
      complex and consequently, electrical field can be used to modulate the
      association between the thrombin and its aptamer.

PMID- 27874043
TI  - Correlation analysis of the mRNA and miRNA expression profiles in the nascent
      synthetic allotetraploid Raphanobrassica.
AB  - Raphanobrassica is an allopolyploid species derived from inter-generic
      hybridization that combines the R genome from R. sativus and the C genome from B.
      oleracea var. alboglabra. In the present study, we used a high-throughput
      sequencing method to identify the mRNA and miRNA profiles in Raphanobrassica and
      its parents. A total of 33,561 mRNAs and 283 miRNAs were detected, 9,209 mRNAs
      and 134 miRNAs were differentially expressed respectively, 7,633 mRNAs and 39
      miRNAs showed ELD expression, 5,219 mRNAs and 57 miRNAs were non-additively
      expressed in Raphanobrassica. Remarkably, differentially expressed genes (DEGs)
      were up-regulated and maternal bias was detected in Raphanobrassica. In addition,
      a miRNA-mRNA interaction network was constructed based on reverse regulated miRNA
      mRNAs, which included 75 miRNAs and 178 mRNAs, 31 miRNAs were non-additively
      expressed target by 13 miRNAs. The related target genes were significantly
      enriched in the GO term 'metabolic processes'. Non-additive related target genes
      regulation is involved in a range of biological pathways, like providing a
      driving force for variation and adaption in this allopolyploid. The integrative
      analysis of mRNA and miRNA profiling provides more information to elucidate gene
      expression mechanism and may supply a comprehensive and corresponding method to
      study genetic and transcription variation of allopolyploid.

PMID- 27874044
TI  - New Fluoride-arsenide Diluted Magnetic Semiconductor (Ba,K)F(Zn,Mn)As with
      Independent Spin and Charge Doping.
AB  - We report the discovery of a new fluoride-arsenide bulk diluted magnetic
      semiconductor (Ba,K)F(Zn,Mn)As with the tetragonal ZrCuSiAs-type structure which
      is identical to that of the "1111" iron-based superconductors. The joint hole
      doping via (Ba,K) substitution &spin doping via (Zn,Mn) substitution results in
      ferromagnetic order with Curie temperature up to 30 K and demonstrates that the
      ferromagnetic interactions between the localized spins are mediated by the
      carriers. Muon spin relaxation measurements confirm the intrinsic nature of the
      long range magnetic order in the entire volume in the ferromagnetic phase. This
      is the first time that a diluted magnetic semiconductor with decoupled spin and
      charge doping is achieved in a fluoride compound. Comparing to the isostructure
      oxide counterpart of LaOZnSb, the fluoride DMS (Ba,K)F(Zn,Mn)As shows much
      improved semiconductive behavior that would be benefit for further application
      developments.

PMID- 27874046
TI  - Body height as risk factor for emphysema in COPD.
AB  - Pulmonary emphysema is a phenotypic component of chronic obstructive pulmonary
      disease (COPD) which carries substantial morbidity and mortality. We explored the
      association between emphysema and body height in 726 patients with COPD using
      computed tomography as the reference diagnostic standard for emphysema. We
      applied univariate analysis to look for differences between patients with
      emphysema and those without, and multivariate logistic regression to identify
      significant predictors of the risk of emphysema. As covariates we included age,
      sex, body height, body mass index, pack-years of smoking, and forced expiratory
      volume in one second (FEV1) as percent predicted. The overall prevalence of
      emphysema was 52%. Emphysemic patients were significantly taller and thinner than
      non-emphysemic ones, and featured significantly higher pack-years of smoking and
      lower FEV1 (P < 0.001). The prevalence of emphysema rose linearly by 10-cm
      increase in body height (r2 = 0.96). In multivariate analysis, the odds of
      emphysema increased by 5% (95% confidence interval, 3 to 7%) along with one
      centimeter increase in body height, and remained unchanged after adjusting for
      all the potential confounders considered (P < 0.001). The odds of emphysema were
      not statistically different between males and females. In conclusion, body height
      is a strong, independent risk factor for emphysema in COPD.

PMID- 27874045
TI  - Morphological and proteomic analysis of biofilms from the Antarctic archaeon,
      Halorubrum lacusprofundi.
AB  - Biofilms enhance rates of gene exchange, access to specific nutrients, and cell
      survivability. Haloarchaea in Deep Lake, Antarctica, are characterized by high
      rates of intergenera gene exchange, metabolic specialization that promotes niche
      adaptation, and are exposed to high levels of UV-irradiation in summer.
      Halorubrum lacusprofundi from Deep Lake has previously been reported to form
      biofilms. Here we defined growth conditions that promoted the formation of
      biofilms and used microscopy and enzymatic digestion of extracellular material to
      characterize biofilm structures. Extracellular DNA was found to be critical to
      biofilms, with cell surface proteins and quorum sensing also implicated in
      biofilm formation. Quantitative proteomics was used to define pathways and
      cellular processes involved in forming biofilms; these included enhanced purine
      synthesis and specific cell surface proteins involved in DNA metabolism; post
      translational modification of cell surface proteins; specific pathways of carbon
      metabolism involving acetyl-CoA; and specific responses to oxidative stress. The
      study provides a new level of understanding about the molecular mechanisms
      involved in biofilm formation of this important member of the Deep Lake
      community.

PMID- 27874047
TI  - Energetics of vacancy segregation to [100] symmetric tilt grain boundaries in bcc
      tungsten.
AB  - The harsh irradiation environment poses serious threat to the structural
      integrity of leading candidate for plasma-facing materials, tungsten (W), in
      future nuclear fusion reactors. It is thus essential to understand the radiation
      induced segregation of native defects and impurities to defect sinks, such as
      grain boundaries (GBs), by quantifying the segregation energetics. In this work,
      molecular statics simulations of a range of equilibrium and metastable [100]
      symmetric tilt GBs are carried out to explore the energetics of vacancy
      segregation. We show that the low-angle GBs have larger absorption length scales
      over their high-angle counterparts. Vacancy sites that are energetically
      unfavorable for segregation are found in all GBs. The magnitudes of minimum
      segregation energies for the equilibrium GBs vary from -2.61 eV to -0.76 eV
      depending on the GB character, while those for the metastable GB states tend to
      be much lower. The significance of vacancy delocalization in decreasing the
      vacancy segregation energies and facilitating GB migration has been discussed.
      Metrics such as GB energy and local stress are used to interpret the simulation
      results, and correlations between them have been established. This study
      contributes to the possible application of polycrystalline W under irradiation in
      advanced nuclear fusion reactors.

PMID- 27874048
TI  - Inverse changes in L1 retrotransposons between blood and brain in major
      depressive disorder.
AB  - Long interspersed nuclear element-1 (LINE-1 or L1) is a type of retrotransposons
      comprising 17% of the human and mouse genome, and has been found to be associated
      with several types of neurological disorders. Previous post-mortem brain studies
      reveal increased L1 copy number in the prefrontal cortex from schizophrenia
      patients. However, whether L1 retrotransposition occurs similarly in major
      depressive disorder (MDD) is unknown. Here, L1 copy number was measured by
      quantitative PCR analysis in peripheral blood of MDD patients (n = 105) and
      healthy controls (n = 105). The results showed that L1 copy number was increased
      in MDD patients possibly due to its hypomethylation. Furthermore, L1 copy number
      in peripheral blood and five brain regions (prefrontal cortex, hippocampus,
      amygdala, nucleus accumbens and paraventricular hypothalamic nucleus) was
      measured in the chronic unpredictable mild stress (CUMS) model of depression in
      mice. Intriguingly, increased L1 copy number in blood and the decreased L1 copy
      number in the prefrontal cortex were observed in stressed mice, while no change
      was found in other brain regions. Our results suggest that the changes of L1 may
      be associated with the pathophysiology of MDD, but the biological mechanism
      behind dysfunction of L1 retrotransposition in MDD remains to be further
      investigated.

PMID- 27874049
TI  - Control on Surface Plasmon Polaritons Propagation Properties by Continuously
      Moving a Nanoparticle along a Silver Nanowire Waveguide.
AB  - Surface plasmon polaritons (SPPs)-based nanowire waveguides possess potential
      applications for nanophotonic circuits. Precise control on the propagation of
      SPPs in metal nanowires is thus of significant importance. In this work, we
      report the control on SPPs propagation properties by moving a silver nanoparticle
      (Ag NP) along a silver nanowire (Ag NW). The emission intensity at NP can be
      attenuated to about 25% of the maximum emission value with increasing the
      distance between excitation end and NP. When NP is gradually moved away from
      excitation end, the intensity of emission light at Ag NP shows an exponential
      decay with a superposition of wavy appearance, while the emission at NW end is
      almost a constant value. It is found that the former is related to the local SPPs
      field distribution in NW, and the latter is dependent on the distance between
      excitation end and NW terminal. Moreover, the propagation loss in Ag NP-NW
      structure has been investigated. Our experiments demonstrate the important role
      of NP location in NW-based waveguides and provide an effective method of tuning
      scattering light in NW, which is instructive to design the future specialized
      function of SPPs-based nanophotonic circuits and devices.

PMID- 27874050
TI  - Automatic Identification of Systolic Time Intervals in Seismocardiogram.
AB  - Continuous and non-invasive monitoring of hemodynamic parameters through
      unobtrusive wearable sensors can potentially aid in early detection of cardiac
      abnormalities, and provides a viable solution for long-term follow-up of patients
      with chronic cardiovascular diseases without disrupting the daily life
      activities. Electrocardiogram (ECG) and siesmocardiogram (SCG) signals can be
      readily acquired from light-weight electrodes and accelerometers respectively,
      which can be employed to derive systolic time intervals (STI). For this purpose,
      automated and accurate annotation of the relevant peaks in these signals is
      required, which is challenging due to the inter-subject morphological variability
      and noise prone nature of SCG signal. In this paper, an approach is proposed to
      automatically annotate the desired peaks in SCG signal that are related to STI by
      utilizing the information of peak detected in the sliding template to narrow-down
      the search for the desired peak in actual SCG signal. Experimental validation of
      this approach performed in conventional/controlled supine and
      realistic/challenging seated conditions, containing over 5600 heart beat cycles
      shows good performance and robustness of the proposed approach in noisy
      conditions. Automated measurement of STI in wearable configuration can provide a
      quantified cardiac health index for long-term monitoring of patients, elderly
      people at risk and health-enthusiasts.

PMID- 27874052
TI  - Multifunctional single beam acoustic tweezer for non-invasive cell/organism
      manipulation and tissue imaging.
AB  - Non-contact precise manipulation of single microparticles, cells, and organisms
      has attracted considerable interest in biophysics and biomedical engineering.
      Similar to optical tweezers, acoustic tweezers have been proposed to be capable
      of manipulating microparticles and even cells. Although there have been concerted
      efforts to develop tools for non-contact manipulation, no alternative to complex,
      unifunctional tweezer has yet been found. Here we report a simple, low-cost,
      multifunctional single beam acoustic tweezer (SBAT) that is capable of
      manipulating an individual micrometer scale non-spherical cell at Rayleigh regime
      and even a single millimeter scale organism at Mie regime, and imaging tissue as
      well. We experimentally demonstrate that the SBAT with an ultralow f-number (f# =
      focal length/aperture size) could manipulate an individual red blood cell and a
      single 1.6 mm-diameter fertilized Zebrafish egg, respectively. Besides, in vitro
      rat aorta images were collected successfully at dynamic foci in which the lumen
      and the outer surface of the aorta could be clearly seen. With the ultralow f
      number, the SBAT offers the combination of large acoustic radiation force and
      narrow beam width, leading to strong trapping and high-resolution imaging
      capabilities. These attributes enable the feasibility of using a single acoustic
      device to perform non-invasive multi-functions simultaneously for biomedical and
      biophysical applications.

PMID- 27874051
TI  - Stable Upconversion Nanohybrid Particles for Specific Prostate Cancer Cell
      Immunodetection.
AB  - Prostate cancer is one of the male killing diseases and early detection of
      prostate cancer is the key for better treatment and lower cost. However, the
      number of prostate cancer cells is low at the early stage, so it is very
      challenging to detect. In this study, we successfully designed and developed
      upconversion immune-nanohybrids (UINBs) with sustainable stability in a
      physiological environment, stable optical properties and highly specific
      targeting capability for early-stage prostate cancer cell detection. The
      developed UINBs were characterized by transmission electron microscopy (TEM), X
      ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), dynamic
      light scattering (DLS) and luminescence spectroscopy. The targeting function of
      the biotinylated antibody nanohybrids were confirmed by immunofluorescence assay
      and western blot analysis. The UINB system is able to specifically detect
      prostate cancer cells with stable and background-free luminescent signals for
      highly sensitive prostate cancer cell detection. This work demonstrates a
      versatile strategy to develop UCNPs based sustainably stable UINBs for sensitive
      diseased cell detection.

PMID- 27874053
TI  - Coherent control of double deflected anomalous modes in ultrathin trapezoid
      shaped slit metasurface.
AB  - Coherent light-matter interaction in ultrathin metamaterials has been
      demonstrated to dynamically modulate intensity, polarization and propagation
      direction of light. The gradient metasurface with a transverse phase variation
      usually exhibits an anomalous refracted beam of light dictated by so-called
      generalized Snell's law. However, less attention has been paid to coherent
      control of the metasurface with multiple anomalous refracted beams. Here we
      propose an ultrathin gradient metasurface with single trapezoid-shaped slot
      antenna as its building block that allows one normal and two deflected
      transmitted beams. It is numerically demonstrated that such metasurface with
      multiple scattering modes can be coherently controlled to modulate output
      intensities by changing the relative phase difference between two
      counterpropagating coherent beams. Each mode can be coherently switched on/off
      and two deflected anomalous beams can be synchronously dictated by the phase
      difference. The coherent control effect in the trapezoid-shaped slit metasurface
      will offer a promising opportunity for multichannel signals modulation,
      multichannel sensing and wave front shaping.

PMID- 27874054
TI  - Combinational Immunotherapy with Allo-DRibble Vaccines and Anti-OX40 Co
      Stimulation Leads to Generation of Cross-Reactive Effector T Cells and Tumor
      Regression.
AB  - It is well-known that vaccines comprising of irradiated whole tumor cells or
      tumor-derived heat shock proteins can generate tumor-specific immune responses.
      In contrast, we showed recently that vaccines composed of autophagosomes
      (DRibbles) derived from syngeneic sarcomas could induce cross-reactive T-cell
      responses and cross-protection against the tumor. This unusual property of
      DRibbles was related to the selective recruitment of defective ribosomal products
      (DRiPs) and other short-lived proteins (SLiPs) into autophagosomes via
      sequestosome (SQSTM1, p62) mediated association of ubiquitinated SLiPs to the
      autophagy gene product LC3. Here, we extend our observations to mammary
      carcinomas from mice of different genetic background. We demonstrated that
      combined of intranodal administration of autologous or allogeneic DRibbles
      together with anti-OX40 antibody led to robust proliferation, expansion, and
      differentiation of memory and effector T cells. We also showed that SLiPs is an
      excellent source of antigen for cross-priming of CD8+ T-cells that recognize
      shared tumor antigens in the context of host MHC class I molecules. Thus, our
      results provide a strong basis for novel clinical trials that combine allogeneic
      "off-the-shelf" DRibble vaccines together with antibodies against co-stimulatory
      molecules.

PMID- 27874057
TI  - Growth Mechanisms of Inductively-Coupled Plasma Torch Synthesized Silicon
      Nanowires and their associated photoluminescence properties.
AB  - Ultra-thin Silicon Nanowires (SiNWs) were produced by means of an industrial
      inductively-coupled plasma (ICP) based process. Two families of SiNWs have been
      identified, namely long SiNWs (up to 2-3 micron in length) and shorter ones (~100
      nm). SiNWs were found to consist of a Si core (with diameter as thin as 2 nm) and
      a silica shell, of which the thickness varies from 5 to 20 nm. By combining
      advanced transmission electron microscopy (TEM) techniques, we demonstrate that
      the growth of the long SiNWs occurred via the Oxide Assisted Growth (OAG)
      mechanism, while the Vapor Liquid Solid (VLS) mechanism is responsible for the
      growth of shorter ones. Energy filtered TEM analyses revealed, in some cases, the
      existence of chapelet-like Si nanocrystals embedded in an otherwise silica
      nanowire. Such nanostructures are believed to result from the exposure of some
      OAG SiNWs to high temperatures prevailing inside the reactor. Finally, the
      intense photoluminescence (PL) of these ICP-grown SiNWs in the 620-950 nm
      spectral range is a clear indication of the occurrence of quantum confinement.
      Such a PL emission is in accordance with the TEM results which revealed that the
      size of nanostructures are indeed below the exciton Bohr radius of silicon.

PMID- 27874056
TI  - Genomic regions responsible for amenability to Agrobacterium-mediated
      transformation in barley.
AB  - Different plant cultivars of the same genus and species can exhibit vastly
      different genetic transformation efficiencies. However, the genetic factors
      underlying these differences in transformation rate remain largely unknown. In
      barley, 'Golden Promise' is one of a few cultivars reliable for Agrobacterium
      mediated transformation. By contrast, cultivar 'Haruna Nijo' is recalcitrant to
      genetic transformation. We identified genomic regions of barley important for
      successful transformation with Agrobacterium, utilizing the 'Haruna Nijo' *
      'Golden Promise' F2 generation and genotyping by 124 genome-wide SNP markers. We
      observed significant segregation distortions of these markers from the expected
      1:2:1 ratio toward the 'Golden Promise'-type in regions of chromosomes 2H and 3H,
      indicating that the alleles of 'Golden Promise' in these regions might contribute
      to transformation efficiency. The same regions, which we termed Transformation
      Amenability (TFA) regions, were also conserved in transgenic F2 plants generated
      from a 'Morex' * 'Golden Promise' cross. The genomic regions identified herein
      likely include necessary factors for Agrobacterium-mediated transformation in
      barley. The potential to introduce these loci into any haplotype of barley opens
      the door to increasing the efficiency of transformation for target alleles into
      any haplotype of barley by the TFA-based methods proposed in this report.

PMID- 27874055
TI  - The coordinated roles of miR-26a and miR-30c in regulating TGFbeta1-induced
      epithelial-to-mesenchymal transition in diabetic nephropathy.
AB  - MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy.
      Here, we compared the protective efficacies of miR-26a and miR-30c in renal
      tubular epithelial cells (NRK-52E) and determined whether they demonstrated
      additive effects in the attenuation of renal fibrosis. TGFbeta1 suppressed miR
      26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E
      cells, and these changes were also found in the kidney cortex of 40-week-old
      diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Bioinformatic analyses
      and luciferase assays further demonstrated that both miR-26a and miR-30c targeted
      connective tissue growth factor (CTGF); additionally, Snail family zinc finger 1
      (Snail1), a potent epithelial-to-mesenchymal transition (EMT) inducer, was
      targeted by miR-30c. Overexpression of miR-26a and miR-30c coordinately decreased
      CTGF protein levels and subsequently ameliorated TGFbeta1-induced EMT in NRK-52E
      cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect.
      Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK
      activation. Furthermore, miR-26a was up-regulated in urinary extracellular
      vesicles of diabetic nephropathy patients. Our study provides evidence for the
      cooperative roles of miR-26a and miR-30c in the pathogenesis of diabetic
      nephropathy, and the co-targeting of miR-26a and miR-30c could provide a new
      direction for diabetic nephropathy treatment.

PMID- 27874059
TI  - Super-enhancement of 1.54 MUm emission from erbium codoped with oxygen in silicon
      on-insulator.
AB  - We report on the super enhancement of the 1.54 MUm Er emission in erbium doped
      silicon-on-insulator when codoped with oxygen at a ratio of 1:1. This is
      attributed to a more favourable crystal field splitting in the substitutional
      tetrahedral site favoured for the singly coordinated case. The results on these
      carefully matched implant profiles show that optical response is highly
      determined by the amount and ratio of erbium and oxygen present in the sample and
      ratios of O:Er greater than unity are severely detrimental to the Er emission.
      The most efficient luminescence is forty times higher than in silicon-on
      insulator implanted with Er only. This super enhancement now offers a realistic
      route not only for optical communication applications but also for the
      implementation of silicon photonic integrated circuits for sensing, biomedical
      instrumentation and quantum communication.

PMID- 27874058
TI  - Perceptual learning in a non-human primate model of artificial vision.
AB  - Visual perceptual grouping, the process of forming global percepts from discrete
      elements, is experience-dependent. Here we show that the learning time course in
      an animal model of artificial vision is predicted primarily from the density of
      visual elements. Three naive adult non-human primates were tasked with
      recognizing the letters of the Roman alphabet presented at variable size and
      visualized through patterns of discrete visual elements, specifically, simulated
      phosphenes mimicking a thalamic visual prosthesis. The animals viewed a spatially
      static letter using a gaze-contingent pattern and then chose, by gaze fixation,
      between a matching letter and a non-matching distractor. Months of learning were
      required for the animals to recognize letters using simulated phosphene vision.
      Learning rates increased in proportion to the mean density of the phosphenes in
      each pattern. Furthermore, skill acquisition transferred from trained to
      untrained patterns, not depending on the precise retinal layout of the simulated
      phosphenes. Taken together, the findings suggest that learning of perceptual
      grouping in a gaze-contingent visual prosthesis can be described simply by the
      density of visual activation.

PMID- 27874060
TI  - Close relationship between a dry-wet transition and a bubble rearrangement in two
      dimensional foam.
AB  - Liquid foams are classified into a dry foam and a wet foam, empirically judging
      from the liquid fraction or the shape of the gas bubbles. It is known that
      physical properties such as elasticity and diffusion are different between the
      dry foam and the wet foam. Nevertheless, definitions of those states have been
      vague and the dry-wet transition of foams has not been clarified yet. Here we
      show that the dry-wet transition is closely related to rearrangement of the gas
      bubbles, by simultaneously analysing the shape change of the bubbles and that of
      the entire foam in two dimensional foam. In addition, we also find a new state in
      quite low liquid fraction, which is named "superdry foam". Whereas the shape
      change of the bubbles strongly depends on the change of the liquid fraction in
      the superdry foam, the shape of the bubbles does not change with changing the
      liquid fraction in the dry foam. Our results elucidate the relationship between
      the transitions and the macroscopic mechanical properties.

PMID- 27874063
TI  - CNS cancer: Tracing stem cells in oligodendroglioma.

PMID- 27874064
TI  - Prostate cancer: Screening and treatment: where do we go from here?

PMID- 27874061
TI  - Strategies to avoid treatment-induced lineage crisis in advanced prostate cancer.
AB  - The increasing potency of therapies that target the androgen receptor (AR)
      signalling axis has correlated with a rise in the proportion of patients with
      prostate cancer harbouring an adaptive phenotype, termed treatment-induced
      lineage crisis. This phenotype is characterized by features that include soft
      tissue metastasis and/or resistance to standard anticancer therapies. Potent
      anticancer treatments might force cancer cells to evolve and develop alternative
      cell lineages that are resistant to primary therapies, a mechanism similar to the
      generation of multidrug- resistant microorganisms after continued antibiotic use.
      Herein, we assess the hypothesis that treatment-adapted phenotypes harbour
      reduced AR expression and/or activity, and acquire compensatory strategies for
      cell survival. We highlight the striking similarities between castration
      resistant prostate cancer and triple-negative breast cancer, another poorly
      differentiated endocrine malignancy. Alternative treatment paradigms are needed
      to avoid therapy-induced resistance. Herein, we present a new clinical trial
      strategy designed to evaluate the potential of rapid drug cycling as an approach
      to delay the onset of resistance and treatment-induced lineage crisis in patients
      with metastatic castration-resistant prostate cancer.

PMID- 27874065
TI  - Antimicrobial Peptide Potency is Facilitated by Greater Conformational
      Flexibility when Binding to Gram-negative Bacterial Inner Membranes.
AB  - The interaction of antimicrobial peptides (AMPs) with the inner membrane of Gram
      negative bacteria is a key determinant of their abilities to exert diverse
      bactericidal effects. Here we present a molecular level understanding of the
      initial target membrane interaction for two cationic alpha-helical AMPs that
      share structural similarities but have a ten-fold difference in antibacterial
      potency towards Gram-negative bacteria. The binding and insertion from solution
      of pleurocidin or magainin 2 to membranes representing the inner membrane of Gram
      negative bacteria, comprising a mixture of 128 anionic and 384 zwitterionic
      lipids, is monitored over 100 ns in all atom molecular dynamics simulations. The
      effects of the membrane interaction on both the peptide and lipid constituents
      are considered and compared with new and published experimental data obtained in
      the steady state. While both magainin 2 and pleurocidin are capable of disrupting
      bacterial membranes, the greater potency of pleurocidin is linked to its ability
      to penetrate within the bacterial cell. We show that pleurocidin displays much
      greater conformational flexibility when compared with magainin 2, resists self
      association at the membrane surface and penetrates further into the hydrophobic
      core of the lipid bilayer. Conformational flexibility is therefore revealed as a
      key feature required of apparently alpha-helical cationic AMPs for enhanced
      antibacterial potency.

PMID- 27874062
TI  - Systemic, perioperative management of muscle-invasive bladder cancer and future
      horizons.
AB  - Many patients diagnosed with muscle-invasive bladder cancer (MIBC) will develop
      distant metastatic disease. Over the past three decades, perioperative cisplatin
      based chemotherapy has been investigated for its ability to reduce the number of
      deaths from bladder cancer. Insufficient evidence is available to fully support
      the use of such chemotherapy in the adjuvant setting; however, neoadjuvant
      cisplatin-based combination chemotherapy has become a standard of care for
      eligible patients based on the improved disease-specific and overall survival
      demonstrated in two randomized phase III trials, compared with surgery alone. For
      patients with disease downstaging to non-MIBC at the time of radical cystectomy
      as a result of neoadjuvant chemotherapy, outcomes are outstanding, with 5-year
      overall survival of 80-90%. Nevertheless, the inability to define before
      treatment the patients who will and those who will not achieve such a response
      has impeded the achievement of better outcomes for patients with MIBC. High
      throughput DNA and RNA profiling technologies might help to overcome this barrier
      and enable a more-personalized approach to the use of cytotoxic neoadjuvant
      chemotherapy. In the past 2 years, trial results have demonstrated the
      unprecedented ability of immune- checkpoint blockade to induce durable remissions
      in patients with metastatic disease that has progressed after chemotherapy;
      studies are now urgently needed to determine how best to incorporate this
      powerful therapeutic modality into the care of patients with MIBC. Herein, we
      review the evolution of chemotherapy and immunotherapy for muscle-invasive
      bladder cancer.

PMID- 27874066
TI  - CL316,243, a beta3-adrenergic receptor agonist, induces muscle hypertrophy and
      increased strength.
AB  - Studies in vitro have demonstrated that beta3-adrenergic receptors (beta3-ARs)
      regulate protein metabolism in skeletal muscle by promoting protein synthesis and
      inhibiting protein degradation. In this study, we evaluated whether activation of
      beta3-ARs by the selective agonist CL316,243 modifies the functional and
      structural properties of skeletal muscles of healthy mice. Daily injections of
      CL316,243 for 15 days resulted in a significant improvement in muscle force
      production, assessed by grip strength and weight tests, and an increased myofiber
      cross-sectional area, indicative of muscle hypertrophy. In addition, atomic force
      microscopy revealed a significant effect of CL316,243 on the transversal
      stiffness of isolated muscle fibers. Interestingly, the expression level of
      mammalian target of rapamycin (mTOR) downstream targets and neuronal nitric oxide
      synthase (NOS) was also found to be enhanced in tibialis anterior and soleus
      muscles of CL316,243 treated mice, in accordance with previous data linking beta3
      ARs to mTOR and NOS signaling pathways. In conclusion, our data suggest that
      CL316,243 systemic administration might be a novel therapeutic strategy worthy of
      further investigations in conditions of muscle wasting and weakness associated
      with aging and muscular diseases.

PMID- 27874067
TI  - 5-HTR3 and 5-HTR4 located on the mitochondrial membrane and functionally
      regulated mitochondrial functions.
AB  - 5-HT has been reported to possess significant effects on cardiac activities, but
      activation of 5-HTR on the cell membrane failed to illustrate the controversial
      cardiac reaction. Because 5-HT constantly comes across the cell membrane via 5-HT
      transporter (5-HTT) into the cytoplasm, whether 5-HTR is functional present on
      the cellular organelles is unknown. Here we show 5-HTR3 and 5-HTR4 were located
      in cardiac mitochondria, and regulated mitochondrial activities and cellular
      functions. Knock down 5-HTR3 and 5-HTR4 in neonatal cardiomyocytes resulted in
      significant increase of cell damage in response to hypoxia, and also led to
      alternation in heart beating. Activation of 5-HTR4 attenuated mitochondrial Ca2+
      uptake under the both normoxic and hypoxic conditions, whereas 5-HTR3 augmented
      Ca2+ uptake only under hypoxia. 5-HTR3 and 5-HTR4 exerted the opposite effects on
      the mitochondrial respiration: 5-HTR3 increased RCR (respiration control ratio),
      but 5-HTR4 reduced RCR. Moreover, activation of 5-HTR3 and 5-HTR4 both
      significantly inhibited the opening of mPTP. Our results provided the first
      evidence that 5-HTR as a GPCR and an ion channel, functionally expressed in
      mitochondria and participated in the mitochondria function and regulation to
      maintain homeostasis of mitochondrial [Ca2+], ROS, and ATP generation efficiency
      in cardiomyocytes in response to stress and O2 tension.

PMID- 27874069
TI  - Direct observation of electronic-liquid-crystal phase transitions and their
      microscopic origin in La1/3Ca2/3MnO3.
AB  - The ground-state electronic order in doped manganites is frequently associated
      with a lattice modulation, contributing to their many interesting properties.
      However, measuring the thermal evolution of the lattice superstructure with
      reciprocal-space probes alone can lead to ambiguous results with competing
      interpretations. Here we provide direct observations of the evolution of the
      superstructure in La1/3Ca2/3MnO3 in real space, as well as reciprocal space,
      using transmission electron microscopic (TEM) techniques. We show that the
      transitions are the consequence of a proliferation of dislocations plus
      electronic phase separation. The resulting states are well described by the
      symmetries associated with electronic-liquid-crystal (ELC) phases. Moreover, our
      results resolve the long-standing controversy over the origin of the
      incommensurate superstructure and suggest a new structural model that is
      consistent with recent theoretical calculations.

PMID- 27874068
TI  - Identification of inhibitors that dually target the new permeability pathway and
      dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum.
AB  - Plasmodium parasites are responsible for the devastating disease malaria that
      affects hundreds of millions of people each year. Blood stage parasites establish
      new permeability pathways (NPPs) in infected red blood cell membranes to
      facilitate the uptake of nutrients and removal of parasite waste products.
      Pharmacological inhibition of the NPPs is expected to lead to nutrient starvation
      and accumulation of toxic metabolites resulting in parasite death. Here, we have
      screened a curated library of antimalarial compounds, the MMV Malaria Box,
      identifying two compounds that inhibit NPP function. Unexpectedly, metabolic
      profiling suggested that both compounds also inhibit dihydroorotate dehydrogense
      (DHODH), which is required for pyrimidine synthesis and is a validated drug
      target in its own right. Expression of yeast DHODH, which bypasses the need for
      the parasite DHODH, increased parasite resistance to these compounds. These
      studies identify two potential candidates for therapeutic development that
      simultaneously target two essential pathways in Plasmodium, NPP and DHODH.

PMID- 27874070
TI  - Waterborne aripiprazole blunts the stress response in zebrafish.
AB  - Here we provide, at least to our knowledge, the first evidence that aripiprazole
      (APPZ) in the water blunts the stress response of exposed fish in a concentration
      ten times lower than the concentration detected in the environment. Although the
      mechanism of APPZ in the neuroendocrine axis is not yet determined, our results
      highlight that the presence of APPZ residues in the environment may interfere
      with the stress responses in fish. Since an adequate stress response is crucial
      to restore fish homeostasis after stressors, fish with impaired stress response
      may have trouble to cope with natural and/or imposed stressors with consequences
      to their welfare and survival.

PMID- 27874071
TI  - An ancient role for nitric oxide in regulating the animal pelagobenthic life
      cycle: evidence from a marine sponge.
AB  - In many marine invertebrates, larval metamorphosis is induced by environmental
      cues that activate sensory receptors and signalling pathways. Nitric oxide (NO)
      is a gaseous signalling molecule that regulates metamorphosis in diverse
      bilaterians. In most cases NO inhibits or represses this process, although it
      functions as an activator in some species. Here we demonstrate that NO positively
      regulates metamorphosis in the poriferan Amphimedon queenslandica. High rates of
      A. queenslandica metamorphosis normally induced by a coralline alga are inhibited
      by an inhibitor of nitric oxide synthase (NOS) and by a NO scavenger. Consistent
      with this, an artificial donor of NO induces metamorphosis even in the absence of
      the alga. Inhibition of the ERK signalling pathway prevents metamorphosis in
      concert with, or downstream of, NO signalling; a NO donor cannot override the ERK
      inhibitor. NOS gene expression is activated late in embryogenesis and in larvae,
      and is enriched in specific epithelial and subepithelial cell types, including a
      putative sensory cell, the globular cell; DAF-FM staining supports these cells
      being primary sources of NO. Together, these results are consistent with NO
      playing an activating role in induction of A. queenslandica metamorphosis,
      evidence of its highly conserved regulatory role in metamorphosis throughout the
      Metazoa.

PMID- 27874072
TI  - Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular
      Dynamics Simulations.
AB  - The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9)
      along with a single guide RNA (sgRNA) has emerged as a versatile toolbox for
      genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA
      mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still
      unclear how the catalytic Mg2+ ions induce the conformation changes toward the
      catalytic active state. It also remains controversial whether Cas9 generates
      blunt-ended or staggered-ended breaks with overhangs in the DNA. To investigate
      these issues, here we performed the first all-atom molecular dynamics simulations
      of the spCas9-sgRNA-dsDNA system with and without Mg2+ bound. The simulation
      results showed that binding of two Mg2+ ions at the RuvC domain active site could
      lead to structurally and energetically favorable coordination ready for the non
      target DNA strand cleavage. Importantly, we demonstrated with our simulations
      that Cas9-catalyzed DNA cleavage produces 1-bp staggered ends rather than
      generally assumed blunt ends.

PMID- 27874073
TI  - Loss-of-function of an Arabidopsis NADPH pyrophosphohydrolase, AtNUDX19, impacts
      on the pyridine nucleotides status and confers photooxidative stress tolerance.
AB  - The levels and redox states of pyridine nucleotides, such as NADP(H), regulate
      the cellular redox homeostasis, which is crucial for photooxidative stress
      response in plants. However, how they are controlled is poorly understood. An
      Arabidopsis Nudix hydrolase, AtNUDX19, was previously identified to have NADPH
      hydrolytic activity in vitro, suggesting this enzyme to be a regulator of the
      NADPH status. We herein examined the physiological role of AtNUDX19 using its
      loss-of-function mutants. NADPH levels were increased in nudx19 mutants under
      both normal and high light conditions, while NADP+ and NAD+ levels were
      decreased. Despite the high redox states of NADP(H), nudx19 mutants exhibited
      high tolerance to moderate light- or methylviologen-induced photooxidative
      stresses. This tolerance might be partially attributed to the activation of
      either or both photosynthesis and the antioxidant system. Furthermore, a
      microarray analysis suggested the role of ANUDX19 in regulation of the salicylic
      acid (SA) response in a negative manner. Indeed, nudx19 mutants accumulated SA
      and showed high sensitivity to the hormone. Our findings demonstrate that ANUDX19
      acts as an NADPH pyrophosphohydrolase to modulate cellular levels and redox
      states of pyridine nucleotides and fine-tunes photooxidative stress response
      through the regulation of photosynthesis, antioxidant system, and possibly
      hormonal signaling.

PMID- 27874074
TI  - Second-trimester urine nephrin:creatinine ratio versus soluble fms-like tyrosine
      kinase-1:placental growth factor ratio for prediction of preeclampsia among
      asymptomatic women.
AB  - This prospective observational study compare urine nephrin:creatinine ratio (NCR,
      ng/mg) with serum soluble fms-like tyrosine kinase-1:placental growth factor
      ratio (FPR, pg/pg) for preeclampsia (PE) prediction among unselected asymptomatic
      pregnant women in 2nd trimester. NCR and FPR were determined in 254 paired
      urine/blood samples collected simultaneously from 254 women at median gestational
      week (GW) 24 (range, 22-27) without hypertension or significant proteinuria in
      pregnancy (SPIP). Fifteen (5.9%) developed SPIP and hypertension at GW 34.0 (26.0
      38.6) and 35.3 (27.6-38.6), respectively, and were diagnosed with PE at GW 35.7
      (27.6-38.6). The 90th percentile level determined in 239 women normotensive
      throughout pregnancy gave NCR (139) sensitivity and positive predictive values
      (PPV) of 60% (9/15) and 27% (9/33), while those for serum FPR (4.85) were 40%
      (6/15) and 20% (6/30), respectively. Relative risks (95%CI) of later PE were 10.0
      (3.82-26.4; 27% [9/33] vs. 2.7% [6/221]) and 4.98 (1.91-13.0; 20% [6/30] vs. 4.0%
      [9/224]) for NCR-positive and FPR-positive women, respectively. Cut-offs
      suggested by ROC gave NCR (86.6) sensitivity and PPV of 87% (13/15) and 17%
      (13/79), and FPR (8.8) values of 40% (6/15) and 40% (6/15), respectively. Thus,
      2nd trimester NCR was superior to FPR for PE prediction.

PMID- 27874075
TI  - A Rapid Response Thin-Film Plasmonic-Thermoelectric Light Detector.
AB  - Light detection and quantification is fundamental to the functioning of a broad
      palette of technologies. While expensive avalanche photodiodes and
      superconducting bolometers are examples of detectors achieving single-photon
      sensitivity and time resolutions down to the picosecond range, thermoelectric
      based photodetectors are much more affordable alternatives that can be used to
      measure substantially higher levels of light power (few kW/cm2). However, in
      thermoelectric detectors, achieving broadband or wavelength-selective performance
      with high sensitivity and good temporal resolution requires careful design of the
      absorbing element. Here, combining the high absorptivity and low heat capacity of
      a nanoengineered plasmonic thin-film absorber with the robustness and linear
      response of a thermoelectric sensor, we present a hybrid detector for visible and
      near-infrared light achieving response times of the order of 100 milliseconds,
      almost four times shorter than the same thermoelectric device covered with a
      conventional absorber. Furthermore, we show an almost two times higher light-to
      electricity efficiency upon replacing the conventional absorber with a plasmonic
      absorber. With these improvements, which are direct results of the efficiency and
      ultra-small thickness of the plasmonic absorber, this hybrid detector constitutes
      an ideal component for various medium-intensity light sensing applications
      requiring spectrally tailored absorption coatings with either broadband or
      narrowband characteristics.

PMID- 27874076
TI  - Oligofructose as an adjunct in treatment of diabetes in NOD mice.
AB  - In type 1 diabetes, restoration of normoglycemia can be achieved if the
      autoimmune attack on beta cells ceases and insulin requirement is met by the
      residual beta cells. We hypothesize that an adjunctive therapy that reduces
      insulin demand by increasing insulin sensitivity will improve the efficacy of an
      immunotherapy in reversing diabetes. We tested the gut microbiota-modulating
      prebiotic, oligofructose (OFS), as the adjunctive therapy. We treated non-obese
      diabetic mice with an immunotherapy, monoclonal anti-CD3 antibody (aCD3), with or
      without concurrent dietary supplement of OFS. After 8 weeks of OFS supplement,
      the group that received both aCD3 and OFS (aCD3 + OFS) had a higher diabetes
      remission rate than the group that received aCD3 alone. The aCD3 + OFS group had
      higher insulin sensitivity accompanied by reduced lymphocytic infiltrate into the
      pancreatic islets, higher beta-cell proliferation rate, higher pancreatic insulin
      content, and secreted more insulin in response to glucose. The addition of OFS
      also caused a change in gut microbiota, with a higher level of Bifidobacterium
      and lower Clostridium leptum. Hence, our results suggest that OFS can potentially
      be an effective therapeutic adjunct in the treatment of type 1 diabetes by
      improving insulin sensitivity and beta-cell function, leading to improved
      glycemic control.

PMID- 27874078
TI  - Glutamate dehydrogenase activator BCH stimulating reductive amination prevents
      high fat/high fructose diet-induced steatohepatitis and hyperglycemia in C57BL/6J
      mice.
AB  - Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes
      (T2D) induced by high calorie western diet are characterized by enhanced
      lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination
      may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis
      toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate
      high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive
      amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)
      heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and
      gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase
      in primary hepatocytes. Long-term BCH treatment improved most metabolic
      alterations induced by high fat/high fructose (HF/HFr) diet in C57BL/6J mice. BCH
      prevented HF/HFr-induced fat accumulation and activation of stress/inflammation
      signals such as phospho-JNK, phospho-PERK, phospho-p38, and phospho-NFkappaB in
      liver tissues. Furthermore, BCH treatment reduced the expression levels of
      inflammatory cytokines such as TNF-alpha and IL-1beta in HF/HFr-fed mouse liver.
      BCH also reduced liver collagen and plasma levels of alanine transaminase and
      aspartate transaminase. On the other hand, BCH significantly improved fasting
      hyperglycemia and glucose tolerance in HF/HFr-fed mice. In conclusion,
      stimulation of reductive amination through GDH activation can be used as a
      strategy to prevent high calorie western diet-induced NAFLD and T2D.

PMID- 27874079
TI  - Crosstalk among proteome, acetylome and succinylome in colon cancer HCT116 cell
      treated with sodium dichloroacetate.
AB  - Protein lysine acetylation and succinylation play important regulatory roles in
      cells, both of which or each other has a close relationship. Dichloroacetate
      (DCA), a well-known pyruvate dehydrogenase kinase (PDK) inhibitor, has the
      potential to be used as anti-cancer drugs for several tumors including colorectal
      cancer. However, little is known about the potential mechanism of DCA-based
      cancer therapy by protein posttranslational modifications (PTM) including global
      proteome, acetylome and succinylome. Here the combinations with stable isotope
      labeling (SILAC), antibody affinity enrichment and high resolution LC-MS/MS
      analysis were performed in human colon cancer HCT116 cells. The quantifiable
      proteome was annotated using bioinformatics. In total, 4,518 proteins, 1,436
      acetylation sites, and 671 succinylation sites were quantified, respectively to
      DCA treatment. Among the quantified acetylated sites, 158 were with increased
      level (quantification ratio >1.5) and 145 with decreased level (quantification
      ratio <0.67). Meanwhile, 179 up-regulated and 114 down-regulated succinylated
      sites were identified. The bioinformatics analyses initially showed acetylation
      and succinylation were involved in a wide range of cellular functions upon DCA
      based anti-cancer effects. Notably, protein-protein interaction network analyses
      demonstrated widespread interactions modulated by protein acetylation and
      succinylation. Taken together, this study may shed a light on understanding the
      mechanism of DCA-based cancer treatment.

PMID- 27874077
TI  - Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser
      induced Choroidal Neovascularization.
AB  - Pathological choroidal neovascularization (CNV) is the common cause of vision
      loss in patients with age-related macular degeneration (AMD). Macrophages possess
      potential angiogenic function in CNV. We have demonstrated that human T
      lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in
      several pathological neovascularization models. In this study, we investigated
      the alteration of proangiogenic properties of macrophages by LMPs treatment in
      vitro and in vivo models. LMPs regulated the expression of several angiogenesis
      related factors in macrophages and consequently stimulated their antiangiogenic
      effects evidenced by the suppression of the proliferation of human retinal
      endothelial cells in co-culture experiments. The involvement of CD36 receptor in
      LMPs uptake by macrophages was demonstrated by in vitro assays and by
      immunostaining of choroidal flat mounts. In addition, ex vivo experiments showed
      that CD36 mediates the antiangiogenic effect of LMPs in murine and human
      choroidal explants. Furthermore, intravitreal injection of LMPs in the mouse
      model of laser-induced CNV significantly suppressed CNV in CD36 dependent manner.
      The results of this study suggested an ability of LMPs to alter the gene
      expression pattern of angiogenesis-related factors in macrophages, which provide
      important information for a new therapeutic approach for efficiently interfering
      with both vascular and extravascular components of CNV.

PMID- 27874080
TI  - Integrated omics study of lipid droplets from Plasmodiophora brassicae.
AB  - Plasmodiophora brassicae causes clubroot disease in cruciferous. In this report,
      lipid droplets were observed in the resting spores of P. brassicae. 295 lipid
      droplet-associated proteins were identified and categorized into nine groups.
      Transcriptome analysis of these proteins during three different zoosporic stages
      revealed differences in gene expression pattern. GO enrichment analysis revealed
      that these proteins associated with lipid droplets were mainly linked to
      biosynthesis and metabolism. GC-MS analysis revealed that lipid droplets contain
      seven types of free fatty acids: saturated fatty acids C16:0 and C18:0, and
      unsaturated fatty acids C18:1Delta9, C18:1Delta11, C18:2, C20:4 and C20:5. P.
      brassicae accumulated a large amount of triacylglycerols (TAGs). We
      systematically analyzed the putative proteins involved in TAG biosynthesis and
      its metabolic pathway. KEGG pathway analysis defined 3390 genes, including 167
      genes involved in lipid metabolism. Transcriptome analysis revealed that 162
      candidate enzymes involved in lipid metabolism were differential expressed. Our
      omics studies are the first to investigate the lipid droplet organelles in P.
      brassicae, providing a reference resource to study protist lipid droplets.

PMID- 27874081
TI  - The response of the soil microbial food web to extreme rainfall under different
      plant systems.
AB  - An agroforestry experiment was conducted that involved four planting systems:
      monoculture of the focal species Zanthoxylum bungeanum and mixed cultures of Z.
      bungeanum and Capsicum annuum, Z. bungeanum and Medicago sativa and Z. bungeanum
      and Glycine max. Soil microbial food web (microorganisms and nematodes) was
      investigated under manipulated extreme rainfall in the four planting systems to
      assess whether presence of neighbor species alleviated the magnitude of extreme
      rainfall on nutrient uptake of the focal species by increasing the stability of
      soil food web. Our results indicate that in the focal species and G. max mixed
      culture, leaf nitrogen contents of the focal species were higher than in the
      monoculture and in the other mixed cultures under extreme rainfall. This result
      was mainly due to the significant increase under extreme rainfall of G. max
      species root biomass, resulting in enhanced microbial resistance and subsequent
      net nitrogen mineralization rate and leaf nitrogen uptake for the focal species.
      Differences in functional traits of neighbors had additive effects and led to a
      marked divergence of soil food-web resistance and nutrient uptake of the focal
      species. Climate change can indirectly alleviate focal species via its influence
      on their neighbors.

PMID- 27874082
TI  - Ultra-broadband Reflective Metamaterial with RCS Reduction based on Polarization
      Convertor, Information Entropy Theory and Genetic Optimization Algorithm.
AB  - We proposed an ultra-broadband reflective metamaterial with controlling the
      scattering electromagnetic fields based on a polarization convertor. The unit
      cell of the polarization convertor was composed of a three layers substrate with
      double metallic split-rings structure and a metal ground plane. The proposed
      polarization convertor and that with rotation angle of 90 deg had been employed
      as the "0" and "1" elements to design the digital reflective metamaterial. The
      numbers of the "0" and "1" elements were chosen based on the information entropy
      theory. Then, the optimized combinational format was selected by genetic
      optimization algorithm. The scattering electromagnetic fields had been
      manipulated due to destructive interference, which was attributed to the control
      of phase and amplitude by the proposed polarization convertor. Simulated and
      experimental results indicated that the reflective metamaterial exhibited
      significantly RCS reduction in an ultra-broad frequency band for both normal and
      oblique incidences.

PMID- 27874085
TI  - Silicon deposition in nanopores using a liquid precursor.
AB  - Techniques for depositing silicon into nanosized spaces are vital for the further
      scaling down of next-generation devices in the semiconductor industry. In this
      study, we filled silicon into 3.5-nm-diameter nanopores with an aspect ratio of
      70 by exploiting thermodynamic behaviour based on the van der Waals energy of
      vaporized cyclopentasilane (CPS). We originally synthesized CPS as a liquid
      precursor for semiconducting silicon. Here we used CPS as a gas source in thermal
      chemical vapour deposition under atmospheric pressure because vaporized CPS can
      fill nanopores spontaneously. Our estimation of the free energy of CPS based on
      Lifshitz van der Waals theory clarified the filling mechanism, where CPS vapour
      in the nanopores readily undergoes capillary condensation because of its large
      molar volume compared to those of other vapours such as water, toluene, silane,
      and disilane. Consequently, a liquid-specific feature was observed during the
      deposition process; specifically, condensed CPS penetrated into the nanopores
      spontaneously via capillary force. The CPS that filled the nanopores was then
      transformed into solid silicon by thermal decomposition at 400  degrees C. The
      developed method is expected to be used as a nanoscale silicon filling
      technology, which is critical for the fabrication of future quantum scale silicon
      devices.

PMID- 27874084
TI  - Silymarin attenuates cigarette smoke extract-induced inflammation via
      simultaneous inhibition of autophagy and ERK/p38 MAPK pathway in human bronchial
      epithelial cells.
AB  - Cigarette smoke (CS) is a major risk of chronic obstructive pulmonary disease
      (COPD), contributing to airway inflammation. Our previous study revealed that
      silymarin had an anti-inflammatory effect in CS-exposed mice. In this study, we
      attempt to further elucidate the molecular mechanisms of silymarin in CS extract
      (CSE)-induced inflammation using human bronchial epithelial cells. Silymarin
      significantly suppressed autophagy activation and the activity of ERK/p38 mitogen
      activated protein kinase (MAPK) pathway in Beas-2B cells. We also observed that
      inhibiting the activity of ERK with specific inhibitor U0126 led to reduced
      autophagic level, while knockdown of autophagic gene Beclin-1 and Atg5 decreased
      the levels of ERK and p38 phosphorylation. Moreover, silymarin attenuated CSE
      induced upregulation of inflammatory cytokines TNF-alpha, IL-6 and IL-8 which
      could also be dampened by ERK/p38 MAPK inhibitors and siRNAs for Beclin-1 and
      Atg5. Finally, we validated decreased levels of both autophagy and inflammatory
      cytokines (TNF-alpha and KC) in CS-exposed mice after silymarin treatment. The
      present research has demonstrated that CSE-induced autophagy in bronchial
      epithelia, in synergism with ERK MAPK pathway, may initiate and exaggerate airway
      inflammation. Silymarin could attenuate inflammatory responses through
      intervening in the crosstalk between autophagy and ERK MAPK pathway, and might be
      an ideal agent treating inflammatory pulmonary diseases.

PMID- 27874083
TI  - Poly-L-ornithine enhances migration of neural stem/progenitor cells via promoting
      alpha-Actinin 4 binding to actin filaments.
AB  - The recruitment of neural stem/progenitor cells (NSPCs) for brain restoration
      after injury is a promising regenerative therapeutic strategy. This strategy
      involves enhancing proliferation, migration and neuronal differentation of NSPCs.
      To date, the lack of biomaterials, which facilitate these processes to enhance
      neural regeneration, is an obstacle for the cell replacement therapies. Our
      previous study has shown that NSPCs grown on poly-L-ornithine (PO) could
      proliferate more vigorously and differentiate into more neurons than that on Poly
      L-Lysine (PLL) and Fibronectin (FN). Here, we demonstrate that PO could promote
      migration of NSPCs in vitro, and the underlying mechanism is PO activates alpha
      Actinins 4 (ACTN4), which is firstly certified to be expessed in NSPCs, to
      promote filopodia formation and therefore enhances NSPCs migration. Taken
      together, PO might serve as a better candidate for transplanted biomaterials in
      the regenerative therapeutic strategy, compared with PLL and FN.

PMID- 27874087
TI  - Development of Commercial Thermo-sensitive Genic Male Sterile Rice Accelerates
      Hybrid Rice Breeding Using the CRISPR/Cas9-mediated TMS5 Editing System.
AB  - Hybrid rice breeding offers an important strategy to improve rice production, in
      which the cultivation of a male sterile line is the key to the success of cross
      breeding. CRISPR/Cas9 systems have been widely used in target-site genome
      editing, whereas their application for crop genetic improvement has been rarely
      reported. Here, using the CRISPR/Cas9 system, we induced specific mutations in
      TMS5, which is the most widely applied thermo-sensitive genic male sterility
      (TGMS) gene in China, and developed new "transgene clean" TGMS lines. We designed
      10 target sites in the coding region of TMS5 for targeted mutagenesis using the
      CRISPR/Cas9 system and assessed the potential rates of on- and off-target
      effects. Finally, we established the most efficient construct, the TMS5ab
      construct, for breeding potentially applicable "transgene clean" TGMS lines. We
      also discussed factors that affect the editing efficiency according to the
      characteristics of different target sequences. Notably, using the TMS5ab
      construct, we developed 11 new "transgene clean" TGMS lines with potential
      applications in hybrid breeding within only one year in both rice subspecies. The
      application of our system not only significantly accelerates the breeding of
      sterile lines but also facilitates the exploitation of heterosis.

PMID- 27874086
TI  - Combined administration of anisodamine and neostigmine rescued acute lethal crush
      syndrome through alpha7nAChR-dependent JAK2-STAT3 signaling.
AB  - Previously we showed that Ani (anisodamine)/Neo (neostigmine) combination
      produced anti-shock effect via activating alpha7 nicotinic acetylcholine receptor
      (alpha7nAChR). In this study, we aim to investigate the therapeutic effect and
      underlying mechanisms of Ani/Neo combination in acute lethal crush syndrome (CS).
      In rat and rabbit CS models, Ani/Neo combination increased the 24 h survival
      rates, improved hemodynamics and decreased the levels of creatine kinase, MB
      isoenzyme of creatine kinase, blood urea nitrogen, creatinine, K+ in serum. It
      also decreased the levels of H2O2, myeloperoxidase (MPO) and nitric oxide (NO) in
      serum and compressed muscle in rat CS model. In wild-type (WT) mice with CS,
      Ani/Neo combination increased 24 h survival rate and decreased the levels of
      H2O2, MPO, NO, TNFalpha, IL-6 and IL-10 in compressed muscle. These effects were
      attenuated by alpha7nAChR knockout (KO). Moreover, Ani/Neo combination prevented
      the decrease of phosphorylation of Janus kinase 2 (JAK2) and phosphorylation of
      signal transducer and activator of transcription 3 (STAT3) induced by CS. These
      effects of Ani/Neo in CS mice were cancelled by methyllycaconitine (alpha7nAChR
      antagonist) and alpha7nAChR KO. Collectively, our results demonstrate that
      Ani/Neo combination could produce therapeutic effects in CS. The underlying
      mechanism involves the activation of alpha7nAChR-dependent JAK2-STAT3 signaling
      pathway.

PMID- 27874089
TI  - Robust encoding of scene anticipation during human spatial navigation.
AB  - In a familiar city, people can recall scene views (e.g., a particular street
      corner scene) they could encounter again in the future. Complex objects with
      multiple features are represented by multiple neural units (channels) in the
      brain, but when anticipating a scene view, the kind of feature that is assigned
      to a specific channel is unknown. Here, we studied neural encoding of scene view
      anticipation during spatial navigation, using a novel data-driven analysis to
      evaluate encoding channels. Our encoding models, based on functional magnetic
      resonance imaging (fMRI) activity, provided channel error correction via
      redundant channel assignments that reflected the navigation environment. We also
      found that our encoding models strongly reflected brain activity in the inferior
      parietal gyrus and precuneus, and that details of future scenes were locally
      represented in the superior prefrontal gyrus and temporal pole. Furthermore, a
      decoder associated with the encoding models accurately predicted future scene
      views in both passive and active navigation. These results suggest that the human
      brain uses scene anticipation, mediated especially by parietal and medial
      prefrontal cortical areas, as a robust and effective navigation processing.

PMID- 27874088
TI  - G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory
      neurons.
AB  - Nerve injury-induced downregulation of voltage-gated potassium channel subunit
      Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability
      and neuropathic pain genesis. However, how nerve injury causes this
      downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase
      2, also known as G9a, methylates histone H3 on lysine residue 9 to predominantly
      produce a dynamic histone dimethylation, resulting in condensed chromatin and
      gene transcriptional repression. We showed here that blocking nerve injury
      induced increase in G9a rescued Kcna2 mRNA and protein expression in the
      axotomized DRG and attenuated the development of nerve injury-induced pain
      hypersensitivity. Mimicking this increase decreased Kcna2 mRNA and protein
      expression, reduced Kv current, and increased excitability in the DRG neurons and
      led to spinal cord central sensitization and neuropathic pain-like symptoms. G9a
      mRNA is co-localized with Kcna2 mRNA in the DRG neurons. These findings indicate
      that G9a contributes to neuropathic pain development through epigenetic silencing
      of Kcna2 in the axotomized DRG.

PMID- 27874090
TI  - A novel process of viral vector barcoding and library preparation enables high
      diversity library generation and recombination-free paired-end sequencing.
AB  - Detailed characterization and mapping of oligonucleotide function in vivo is
      generally a very time consuming effort that only allows for hypothesis driven
      subsampling of the full sequence to be analysed. Recent advances in deep
      sequencing together with highly efficient parallel oligonucleotide synthesis and
      cloning techniques have, however, opened up for entirely new ways to map genetic
      function in vivo. Here we present a novel, optimized protocol for the generation
      of universally applicable, barcode labelled, plasmid libraries. The libraries are
      designed to enable the production of viral vector preparations assessing coding
      or non-coding RNA function in vivo. When generating high diversity libraries, it
      is a challenge to achieve efficient cloning, unambiguous barcoding and detailed
      characterization using low-cost sequencing technologies. With the presented
      protocol, diversity of above 3 million uniquely barcoded adeno-associated viral
      (AAV) plasmids can be achieved in a single reaction through a process achievable
      in any molecular biology laboratory. This approach opens up for a multitude of in
      vivo assessments from the evaluation of enhancer and promoter regions to the
      optimization of genome editing. The generated plasmid libraries are also useful
      for validation of sequencing clustering algorithms and we here validate the newly
      presented message passing clustering process named Starcode.

PMID- 27874091
TI  - HMGA1P7-pseudogene regulates H19 and Igf2 expression by a competitive endogenous
      RNA mechanism.
AB  - Recent studies have revealed that pseudogene transcripts can function as
      competing endogenous RNAs, and thereby can also contribute to cancer when
      dysregulated. We have recently identified two pseudogenes, HMGA1P6 and HMGA1P7
      for the HMGA1 gene whose overexpression has a critical role in cancer
      progression. These pseudogenes work as competitive endogenous RNA decoys for
      HMGA1 and other cancer related genes suggesting their role in carcinogenesis.
      Looking for new HMGA1 pseudogene ceRNAs, we performed RNA sequencing technology
      on mouse embryonic fibroblasts deriving from transgenic mice overexpressing
      HMGA1P7. Here, we report that HMGA1P7 mRNA sustains the H19 and Igf2
      overexpression by acting as miRNA decoy. Lastly, the expression of HMGA1P7 was
      significantly correlated with H19 and IGF2 levels in human breast cancer thereby
      suggesting a role for HMGA1P7 deregulation in this neoplasia.

PMID- 27874092
TI  - Spatially differentiated trends in urbanization, agricultural land abandonment
      and reclamation, and woodland recovery in Northern China.
AB  - Uncovering magnitude, trend, and spatial pattern of land cover/land use changes
      (LCLUC) is crucial for understanding mechanisms of LCLUC and assisting land use
      planning and conservation. China has been undergoing unprecedented economic
      growth, massive rural-to-urban migration, and large-scale policy-driven
      ecological restoration, and therefore encountering enormous LCLUC in recent
      decades. However, comprehensive understandings of spatiotemporal LCLUC dynamics
      and underlying mechanisms are still lacking. Based on classification of annual
      LCLU maps from MODIS satellite imagery, we proposed a land change detection
      method to capture significant land change hotspots over Northern China during
      2001-2013, and further analyzed temporal trends and spatial patterns of LCLUC. We
      found rapid decline of agricultural land near urban was predominantly caused by
      urban expansion. The process was especially strong in North China Plain with
      14,057 km2 of urban gain and -21,017 km2 of agricultural land loss. To offset the
      loss of agricultural land, Northeast China Plain and Xinjiang were reclaimed.
      Substantial recovery of forests (49,908 km2) and closed shrubland (60,854 km2)
      occurred in mountainous regions due to abandoned infertile farmland, secondary
      succession, and governmental conservation policies. The spatial patterns and
      trends of LCLUC in Northern China provide information to support effective
      environmental policies towards sustainable development.

PMID- 27874093
TI  - Enterohemorrhagic Escherichia coli promotes the invasion and tissue damage of
      enterocytes infected with Candida albicans in vitro.
AB  - The principal aim of this study was to investigate the in vitro co-infection of
      Caco-2 cells with Candida albicans and enterohemorrhage Escherichia coli (EHEC).
      The ability of both species to colonize or invade the Caco-2 cells was evaluated
      by indirect immunofluorescence and inverted microscopy. The damage to Caco-2
      cells was evaluated by measuring lactate dehydrogenase (LDH) activity. C.
      albicans virulence gene expression (HWP1, ALS3, PLB1, SAP4, and EFG1) was
      evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Compared
      to single infections with enterohemorrhage Escherichia coli or C. albicans, a co
      infection colonized or invaded Caco-2 cells more quickly, and C. albicans tended
      to accumulate more easily, accompanied by the upregulation of related genes. In
      addition, the LDH activity in the co-infected group was higher than in cells
      infected with C. albicans or with enterohemorrhage Escherichia coli, accompanied
      by the upregulation of toxicity-related genes. Using Caco-2 cells as an infection
      model, this study demonstrated that co-infecting in vitro enterocytes with C.
      albicans and enterohemorrhage Escherichia coli enhanced the invasiveness and
      tissue damaging effects of C. albicans.

PMID- 27874094
TI  - Identification of Polo-like kinase 1 interaction inhibitors using a novel cell
      based assay.
AB  - Polo-like kinase 1 (Plk1) plays several roles in cell division and it is a
      recognized cancer drug target. Plk1 levels are elevated in cancer and several
      types of cancer cells are hypersensitive to Plk1 inhibition. Small molecule
      inhibitors of the kinase domain (KD) of Plk1 have been developed. Their
      selectivity is limited, which likely contributes to their toxicity. Polo-like
      kinases are characterized by a Polo-Box Domain (PBD), which mediates interactions
      with phosphorylation substrates or regulators. Inhibition of the PBD could allow
      better selectivity or result in different effects than inhibition of the KD. In
      vitro screens have been used to identify PBD inhibitors with mixed results. We
      developed the first cell-based assay to screen for PBD inhibitors, using
      Bioluminescence Resonance Energy Transfer (BRET). We screened through 112 983
      compounds and characterized hits in secondary biochemical and biological assays.
      Subsequent Structure-Activity Relationship (SAR) analysis on our most promising
      hit revealed that it requires an alkylating function for its activity. In
      addition, we show that the previously reported PBD inhibitors thymoquinone and
      Poloxin are also alkylating agents. Our cell-based assay is a promising tool for
      the identification of new PBD inhibitors with more drug-like profiles using
      larger and more diverse chemical libraries.

PMID- 27874095
TI  - Longitudinal metagenomic profiling of bovine milk to assess the impact of
      intramammary treatment using a third-generation cephalosporin.
AB  - Antimicrobial usage in food animals has a direct impact on human health, and
      approximately 80% of the antibiotics prescribed in the dairy industry are used to
      treat bovine mastitis. Here we provide a longitudinal description of the changes
      in the microbiome of milk that are associated with mastitis and antimicrobial
      therapy. Next-generation sequencing, 16 S rRNA gene quantitative real-time PCR,
      and aerobic culturing were applied to assess the effect of disease and antibiotic
      therapy on the milk microbiome. Cows diagnosed with clinical mastitis associated
      with Gram-negative pathogens or negative aerobic culture were randomly allocated
      into 5 days of Ceftiofur intramammary treatment or remained as untreated
      controls. Serial milk samples were collected from the affected quarter and the
      ipsilateral healthy quarter of the same animal. Milk from the mastitic quarter
      had a higher bacterial load and reduced microbial diversity compared to healthy
      milk. Resolution of the disease was accompanied by increases in diversity indexes
      and a decrease in pathogen relative abundance. Escherichia coli-associated
      mastitic milk samples had a remarkably distinct bacterial profile, dominated by
      Enterobacteriaceae, when compared to healthy milk. However, no differences were
      observed in culture-negative mastitis samples when compared to healthy milk.
      Antimicrobial treatment had no significant effect on clinical cure,
      bacteriological cure, pathogen clearance rate or bacterial load.

PMID- 27874096
TI  - Complex lasso: new entangled motifs in proteins.
AB  - We identify new entangled motifs in proteins that we call complex lassos. Lassos
      arise in proteins with disulfide bridges (or in proteins with amide linkages),
      when termini of a protein backbone pierce through an auxiliary surface of minimal
      area, spanned on a covalent loop. We find that as much as 18% of all proteins
      with disulfide bridges in a non-redundant subset of PDB form complex lassos, and
      classify them into six distinct geometric classes, one of which resembles
      supercoiling known from DNA. Based on biological classification of proteins we
      find that lassos are much more common in viruses, plants and fungi than in other
      kingdoms of life. We also discuss how changes in the oxidation/reduction
      potential may affect the function of proteins with lassos. Lassos and associated
      surfaces of minimal area provide new, interesting and possessing many potential
      applications geometric characteristics not only of proteins, but also of other
      biomolecules.

PMID- 27874097
TI  - Molecular Insight into Affinities of Gallated and Nongallated Proanthocyanidins
      Dimers to Lipid Bilayers.
AB  - Experimental studies have proved the beneficial effects of proanthocyanidins
      (Pas) relating to interaction with the cell membrane. But the detailed mechanisms
      and structure-function relationship was unclear. In present study, molecular
      dynamics (MD) simulations were used to study the interactions of four PA dimers
      with a lipid bilayer composed of 1:1 mixed 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl phosphatidylethanolamine
      (POPE). The results showed that the gallated PA dimers had much higher affinities
      to the bilayer with lower binding free energies compared with nongallated PA
      dimers. The gallated PA dimers penetrated deeper into the bilayer and formed more
      hydrogen bonds (H-bonds) with bilayer oxygen atoms, especially the deeper oxygen
      atoms of the lipids simultaneously, thus inducing stronger lateral expansion of
      the membrane and lipid tails disorder. The present results provided molecular
      insights into the interactions between PA dimers and bio-membranes and agreed
      with our experimental results well. These molecular interactions helped to
      elucidate the structure-function relationship of the PA dimers and provided a
      foundation for a better understanding of the underlying mechanisms of the
      bioactivities of PA oligomers.

PMID- 27874098
TI  - Local expectation violations result in global activity gain in primary visual
      cortex.
AB  - During natural perception, we often form expectations about upcoming input. These
      expectations are usually multifaceted - we expect a particular object at a
      particular location. However, expectations about spatial location and stimulus
      features have mostly been studied in isolation, and it is unclear whether feature
      based expectation can be spatially specific. Interestingly, feature-based
      attention automatically spreads to unattended locations. It is still an open
      question whether the neural mechanisms underlying feature-based expectation
      differ from those underlying feature-based attention. Therefore, establishing
      whether the effects of feature-based expectation are spatially specific may
      inform this debate. Here, we investigated this by inducing expectations of a
      specific stimulus feature at a specific location, and probing the effects on
      sensory processing across the visual field using fMRI. We found an enhanced
      sensory response for unexpected stimuli, which was elicited only when there was a
      violation of expectation at the specific location where participants formed a
      stimulus expectation. The neural consequences of this expectation violation,
      however, spread to cortical locations processing the stimulus in the opposite
      hemifield. This suggests that an expectation violation at one location in the
      visual world can lead to a spatially non-specific gain increase across the visual
      field.

PMID- 27874099
TI  - Pre-dispersal strategies by Quercus schottkyana to mitigate the effects of weevil
      infestation of acorns.
AB  - We investigated how pre-dispersal strategies may mitigate the effects of weevil
      infestation of acorns in a population of Quercus schottkyana, a dominant oak in
      Asian evergreen broad-leaved forests, and assess if weevil infestation
      contributes to low seedling recruitment. We counted the number of acorns
      produced, daily from the end of August to mid-late November for 9 years from 2006
      2014. We also recorded the rate of acorn infestation by weevils and acorn
      germination rates of weekly collections. Annual acorn production was variable,
      but particularly low in 2011 and 2013. There was no trade-off between acorn
      production and acorn dry mass. However, acorns produced later in the season were
      significantly heavier. For most years: (i) the rate of weevil infestation was
      negatively density dependent (a greater proportion of acorns died with increased
      acorn density), (ii) the percentage germination of acorns was positively density
      dependent (proportionately more acorns germinated with increased density), and
      (iii) as the season progressed, the percentage of infested acorns declined while
      germination rates increased. Finally, (iv) maximum acorn production, percentage
      infestation and percentage germination were asynchronous. Although pre-dispersal
      mortality is important it is unlikely to be the primary factor leading to low
      recruitment of oak seedlings.

PMID- 27874100
TI  - Structural basis of TRPA1 inhibition by HC-030031 utilizing species-specific
      differences.
AB  - Pain is a harmful sensation that arises from noxious stimuli. Transient receptor
      potential ankyrin 1 (TRPA1) is one target for studying pain mechanisms. TRPA1 is
      activated by various stimuli such as noxious cold, pungent natural products and
      environmental irritants. Since TRPA1 is an attractive target for pain therapy, a
      few TRPA1 antagonists have been developed and some function as analgesic agents.
      The responses of TRPA1 to agonists and antagonists vary among species and these
      species differences have been utilized to identify the structural basis of
      activation and inhibition mechanisms. The TRPA1 antagonist HC-030031 (HC) failed
      to inhibit frog TRPA1 (fTRPA1) and zebrafish TRPA1 activity induced by
      cinnamaldehyde (CA), but did inhibit human TRPA1 (hTRPA1) in a heterologous
      expression system. Chimeric studies between fTRPA1 and hTRPA1, as well as
      analyses using point mutants, revealed that a single amino acid residue (N855 in
      hTRPA1) significantly contributes to the inhibitory action of HC. Moreover, the
      N855 residue and the C-terminus region exhibited synergistic effects on the
      inhibition by HC. Molecular dynamics simulation suggested that HC stably binds to
      hTRPA1-N855. These findings provide novel insights into the structure-function
      relationship of TRPA1 and could lead to the development of more effective
      analgesics targeted to TRPA1.

PMID- 27874101
TI  - Molecular mechanism of carbon nanotube to activate Subtilisin Carlsberg in polar
      and non-polar organic media.
AB  - In the work, we mainly used molecular dynamics (MD) simulation and protein
      structure network (PSN) to study subtilisin Carlsberg (SC) immobilized onto
      carbon nanotube (CNT) in water, acetonitrile and heptane solvents, in order to
      explore activation mechanism of enzymes in non-aqueous media. The result
      indicates that the affinity of SC with CNT follows the decreasing order of water
      > acetonitrile > heptane. The overall structure of SC and the catalytic triad
      display strong robustness to the change of environments, responsible for the
      activity retaining. However, the distances between two beta-strands of substrate
      binding pocket are significantly expanded by the immobilization in the increasing
      order of water < acetonitrile < heptane, contributing to the highest substrate
      binding energy in heptane media. PSN analysis further reveals that the
      immobilization enhances structural communication paths to the substrate-binding
      pocket, leading to its larger change than the free-enzymes. Interestingly, the
      increase in the number of the pathways upon immobilization is not dependent on
      the absorbed extent but the desorbed one, indicating significant role of shifting
      process of experimental operations in influencing the functional region. In
      addition, some conserved and important hot-residues in the paths are identified,
      providing molecular information for functional modification.

PMID- 27874102
TI  - Development and comparative study of chemosynthesized antigen and mimotope-based
      immunoassays for class-specific analysis of O,O-dimethyl organophosphorus
      pesticides.
AB  - The multi-residue determination of organophosphorus pesticides (OPs) is an
      important task due to the wide application and high toxicity of OPs. However,
      there is no promising immunoassay to monitor the multi-residue of O,O-dimethyl
      OPs. In this study, a monoclonal antibody (mAb) against a generic hapten of O,O
      dimethyl OPs (O,O-dimethyl O-(3-carboxyphenyl)phosphorothioate) was prepared. To
      develop an effective class-specific immunoassay, two strategies were performed to
      select the appropriate coating antigen or competing antigen. On the one hand, a
      total of 20 haptens were chemosynthesized, attached to ovalbumin for use as
      coating antigen candidates, and selected by direct competitive ELISA (dcELISA).
      As a second strategy, mimotopes of the mAb were selected from a random phage
      display peptide library by panning, and the optimum mimotope was expressed as a
      fusion protein and biotinylated in vitro. Based on the selected chemosynthesized
      coating antigen and the biotinylated mimotope fusion protein, two sensitive broad
      specificity dcELISAs were developed. The sensitivity, selectivity and
      practicability of the two immunoassays were compared. The results demonstrated
      that both methods showed similar selectivity and sensitivity and were reliable
      for O,O-dimethyl OP residues screening. However, the screening operation of
      mimotopes was much simpler and safer compared to the preparation of
      chemosynthesized coating antigens.

PMID- 27874103
TI  - Cordyceps collected from Bhutan, an appropriate alternative of Cordyceps
      sinensis.
AB  - Natural Cordyceps collected in Bhutan has been widely used as natural Cordyceps
      sinensis, an official species of Cordyceps used as Chinese medicines, around the
      world in recent years. However, whether Cordyceps from Bhutan could be really
      used as natural C. sinensis remains unknown. Therefore, DNA sequence, bioactive
      components including nucleosides and polysaccharides in twelve batches of
      Cordyceps from Bhutan were firstly investigated, and compared with natural C.
      sinensis. Results showed that the fungus of Cordyceps from Bhutan was C. sinensis
      and the host insect belonged to Hepialidae sp. In addition, nucleosides and their
      bases such as guanine, guanosine, hypoxanthine, uridine, inosine, thymidine,
      adenine, and adenosine, as well as compositional monosaccharides, partial acid or
      enzymatic hydrolysates, molecular weights and contents of polysaccharides in
      Cordyceps from Bhutan were all similar to those of natural C. sinensis. All data
      suggest that Cordyceps from Bhutan is a rational alternative of natural C.
      sinensis, which is beneficial for the improvement of their performance in health
      and medicinal food areas.

PMID- 27874104
TI  - Identifying mutations in Tunisian families with retinal dystrophy.
AB  - Retinal dystrophies (RD) are a rare genetic disorder with high genetic
      heterogeneity. This study aimed at identifying disease-causing variants in
      fifteen consanguineous Tunisian families. Full ophthalmic examination was
      performed. Index patients were subjected to IROme analysis or whole exome
      sequencing followed by homozygosity mapping. All detected variations were
      confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed
      two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel
      homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant
      c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in
      CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes
      detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4
      (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928
      2A > G). Segregation analysis in each family showed that all affected individuals
      were homozygotes and unaffected individuals were either heterozygote carriers or
      homozygous wild type allele. These results confirm the involvement of a large
      number of genes in RD in the Tunisian population.

PMID- 27874105
TI  - Patterns in longitudinal growth of refraction in Southern Chinese children:
      cluster and principal component analysis.
AB  - In the present study we attempt to use hypothesis-independent analysis in
      investigating the patterns in refraction growth in Chinese children, and to
      explore the possible risk factors affecting the different components of
      progression, as defined by Principal Component Analysis (PCA). A total of 637
      first-born twins in Guangzhou Twin Eye Study with 6-year annual visits (baseline
      age 7-15 years) were available in the analysis. Cluster 1 to 3 were classified
      after a partitioning clustering, representing stable, slow and fast progressing
      groups of refraction respectively. Baseline age and refraction, paternal
      refraction, maternal refraction and proportion of two myopic parents showed
      significant differences across the three groups. Three major components of
      progression were extracted using PCA: "Average refraction", "Acceleration" and
      the combination of "Myopia stabilization" and "Late onset of refraction
      progress". In regression models, younger children with more severe myopia were
      associated with larger "Acceleration". The risk factors of "Acceleration"
      included change of height and weight, near work, and parental myopia, while
      female gender, change of height and weight were associated with "Stabilization",
      and increased outdoor time was related to "Late onset of refraction progress". We
      therefore concluded that genetic and environmental risk factors have different
      impacts on patterns of refraction progression.

PMID- 27874106
TI  - Is Leukocyte Telomere Length Related with Lung Cancer Risk?: A Meta-Analysis.
AB  - BACKGROUND: Epidemiological studies have probed the correlation between telomere
      length and the risk of lung cancer, but their findings are inconsistent in this
      regard. The present meta-analysis study has been carried out to demonstrate the
      association between relative telomere length in peripheral blood leukocytes and
      the risk of lung cancer using an established Q-PCR technique. METHODS: A
      systematic search was carried out using PubMed, EMBASE, and ISI before 2015. A
      total of 2925 cases of lung cancer and 2931 controls from 9 studies were employed
      to probe the relationship between lung cancer and telomere length .ORs were used
      at 95% CI. Random-effects models were used to investigate this relationship based
      on the heterogeneity test. Heterogeneity among studies was analyzed employing
      subgroup analysis based on type studies and the year of publication. RESULTS:
      Random-effects meta-analysis revealed that patients with lung cancer were
      expected to have shorter telomere length than the control (1.13, 95% CI: 0.82
      1.81, P=0.46). The summary of the pooled ORs of telomere length in adenocarcinoma
      lung cancer patients was 1 (95%CI=0.68-1.47, I2=93%) compared to patients with
      squamous cell lung cancer, which was 1.78 (95% CI=1.25-2.53, I2=3.9%). The meta
      regression revealed that the effect of telomere length shortening, decreased and
      increased with the year of publication and the age of risks to lung cancer, was
      clearly related to short telomeres lengths. CONCLUSION: Lung cancer risks clearly
      related with short telomeres lengths. In patients with breathing problems, lung
      cancer risk can be predicted by telomere length adjustment with age, sex, and
      smoking.

PMID- 27874108
TI  - Dirac fermions induced in strained zigzag phosphorus nanotubes and their
      applications in field effect transistors.
AB  - In this work, Dirac fermions have been obtained and engineered in one-dimensional
      (1D) zigzag phosphorus nanotubes (ZPNTs). We have performed a comprehensive first
      principles computational study of the electronic properties of ZPNTs with various
      diameters. The results indicate that as the lattice parameter (Lc) along the
      axial direction increases, ZPNTs undergo transitions from metal to semimetal and
      semimetal to semiconductor, whereas Dirac fermions appear at Lc ranging from 3.90
      A to 4.10 A. In particular, a field effect transistor (FET) based on 12-ZPNT
      (with 12 unit cells in the transverse direction) exhibits semiconductor behaviors
      with efficient gate-effect modulation at Lc = 4.60 A. However, only weak gate
      modulation is demonstrated when the nanotube becomes a semimetal at Lc = 4.10 A.
      This study indicates that ZPNTs are profoundly appealing for applications in
      strain sensors. Our findings pave the way for the development of high-performance
      strain-engineered electronics based on Dirac fermions in 1D materials.

PMID- 27874107
TI  - The Effect of Oral Consumption of Probiotics in Prevention of Heart Injury in a
      Rat Myocardial Infarction Model: a Histopathological, Hemodynamic and Biochemical
      Evaluation.
AB  - BACKGROUND: Despite the emerging evidence on beneficial effects of probiotics on
      the cardiovascular system, their impact on the management of ischemic heart
      diseases and its possible mechanism have not been elucidated. METHODS: Four
      viable probiotics bacterial strains, including Bifidobacterium breve,
      Lactobacillus casei, Lactobacillus bulgaricus and Lactobacillus acidophilus, at
      the concentrations of 2*106 colony-forming units/ml were orally administered to
      the rats daily for 14 days before the induction of infarct-like myocardial injury
      using isoproterenol. Subsequently, 24 h after myocardial injury, the right
      carotid artery and the left ventricle were catheterized for recording blood
      pressure and cardiac parameters. At the end of the experiment, the heart was
      removed for the evaluation of histopathological and biochemical parameters, as
      well as tumor necrosis factor-alpha (TNF-alpha) assay. RESULTS: The induction of
      acute myocardial injury resulted in significant (P<=0.01) left ventricular (LV)
      dysfunction, as shown by an increase in LV end-diastolic pressure and a decrease
      in LV dp/dt max, LV dp/dt min, LV systolic pressure, and blood pressure, as
      compared with normal rats. Pretreatment with viable probiotics significantly
      reduced lipid peroxidation and TNF-alpha level and improved cardiac function
      (P<0.01). CONCLUSION: This study shows that viable probiotics have a
      cardioprotective effect on infarct-like myocardial injury through suppressing TNF
      alpha and oxidative stress damage in a rat model. Probiotic supplements may be
      used as a new option for prophylaxis in patients at the risk of ischemic heart
      disease in future.

PMID- 27874110
TI  - Molecular thermodynamics of metabolism: hydration quantities and the equation-of
      state approach.
AB  - The present work is part of a series of papers aiming at a thorough understanding
      of the thermodynamics of metabolism over a broad range of external conditions.
      The focus here is on the systematic study of solvation/hydration of a variety of
      fluids via an equation-of-state approach. This approach permits the study not
      only of the overall free energy, enthalpy or entropy of hydration but also their
      key components from cavitation, charging, and solute conformations/solvent
      restructuring contributions. These latter components shed light into the
      mechanism of hydration and contribute to our understanding of solvation phenomena
      at remote conditions of temperature and pressure. Hydrogen bonding is of central
      importance in this respect and is handled via the partial solvation parameter
      (PSP) approach. The developed solvation model is used for the estimation of the
      hydration quantities of key metabolites. The challenges and perspectives of this
      equation-of-state approach are critically discussed.

PMID- 27874109
TI  - Molecular electrometer and binding of cations to phospholipid bilayers.
AB  - Despite the vast amount of experimental and theoretical studies on the binding
      affinity of cations - especially the biologically relevant Na+ and Ca2+ - for
      phospholipid bilayers, there is no consensus in the literature. Here we show that
      by interpreting changes in the choline headgroup order parameters according to
      the 'molecular electrometer' concept [Seelig et al., Biochemistry, 1987, 26,
      7535], one can directly compare the ion binding affinities between simulations
      and experiments. Our findings strongly support the view that in contrast to Ca2+
      and other multivalent ions, Na+ and other monovalent ions (except Li+) do not
      specifically bind to phosphatidylcholine lipid bilayers at sub-molar
      concentrations. However, the Na+ binding affinity was overestimated by several
      molecular dynamics simulation models, resulting in artificially positively
      charged bilayers and exaggerated structural effects in the lipid headgroups.
      While qualitatively correct headgroup order parameter response was observed with
      Ca2+ binding in all the tested models, no model had sufficient quantitative
      accuracy to interpret the Ca2+:lipid stoichiometry or the induced atomistic
      resolution structural changes. All scientific contributions to this open
      collaboration work were made publicly, using nmrlipids.blogspot.fi as the main
      communication platform.

PMID- 27874111
TI  - First-principles calculations of the electronic structure and bonding in metal
      cluster-fullerene materials considered within the superatomic framework.
AB  - Inspired by recent success of synthesizing cluster assembled compounds we address
      the question to what extent the three new materials [Co6Se8(PEt3)6][C60]2,
      [Cr6Te8(PEt3)6][C60]2, and [Ni9Te6(PEt3)8]C60, upon forming bulk compounds,
      imitate atomic analogues. Although experimental results suggest the latter, a
      theoretical approach is the method of choice for offering a conclusive answer and
      for studying the actual superatomic character. The concept of superatoms for
      describing atom-imitating clusters is very intriguing since it allows chemists to
      apply their chemical intuition - a useful tool for predicting new materials -
      when it comes to inter-cluster reactions. Thus, we systematically study the
      lattice structure, the intercluster binding, and the electronic structure by
      density functional theory and assess them in terms of their superatomic features.
      We show that collective properties arise upon bulk formation, which promotes
      arguments for the formation of solids in which the constituent clusters have a
      superatomic character that determines some form of chemical bonding.
      Additionally, we find evidence for the formation of superatomic states.
      Unfortunately, however, due to the mixing of electronic states of transition
      metals and chalcogen atoms, no typical electronic shell closing in the cluster
      cores can be identified.

PMID- 27874112
TI  - Surface reaction network of CO oxidation on CeO2/Au(110) inverse model catalysts.
AB  - CeO2/Au(110) inverse model catalysts were prepared and their activity toward the
      adsorption and co-adsorption of O2, CO, CO2 and water was studied by means of X
      ray photoelectron spectroscopy, low energy electron diffraction, thermal
      desorption spectra and temperature-programmed reaction spectra. The Au surface of
      CeO2/Au(110) inverse model catalysts molecularly adsorbs CO, CO2 and water, and
      the polycrystalline CeO2 surface of CeO2/Au(110) inverse model catalysts
      molecularly adsorbs O2, and molecularly and reactively adsorbs CO, CO2 and water.
      By controllably preparing co-adsorbed surface species on CeO2/Au(110) inverse
      model catalysts, we successfully identified various surface reaction pathways of
      CO oxidation to produce CO2 with different barriers both on the CeO2 surface and
      at the Au-CeO2 interface, including CO oxidation by various oxygen species, and
      water/hydroxyl group-involved CO oxidation. These results establish a surface
      reaction network of CO oxidation catalyzed by Au/CeO2 catalysts, greatly
      advancing the fundamental understandings of catalytic CO oxidation reactions.

PMID- 27874113
TI  - An atomically thin layer of Ru/MoS2 heterostructure: structural, electronic, and
      magnetic properties.
AB  - The fabrication of a transition metal (TM) atomically thin layer with robust
      ferromagnetic ordering (FM) for the continuous miniaturization of spintronic and
      quantum computing devices is desired. Through first-principles calculations, we
      establish that Ru atoms can be epitaxially aligned on MoS2 monolayers, thus
      forming an atomically thin layer of 2D Ru/MoS2 heterostructure with high
      structural stability. The Ru layer possesses a robust FM (more than 300 K) and an
      out-of-plane easy axis with the magnetic anisotropy energy (MAE) of ~3.4 meV per
      atom. In particular, we find that the FM can be switched by an external electric
      field (Efield) of 1.5 V nm-1. We propose that this atomically thin layer of
      Ru/MoS2 heterostructure can be used as an alternative candidate for free-standing
      magnetic TM layers and provides new possibilities to design 2D spintronic
      devices.

PMID- 27874114
TI  - Supracolloidal fullerene-like cages: design principles and formation mechanisms.
AB  - How to create novel desired structures by rational design of building blocks
      represents a significant challenge in materials science. Here we report a
      conceptually new design principle for creating supracolloidal fullerene-like
      cages through the self-assembly of soft patchy particles interacting via
      directional nonbonded interactions by mimicking non-planar sp2 hybridized carbon
      atoms in C60. Our numerical investigations demonstrate that the rational design
      of patch configuration, size, and interaction can drive soft three-patch
      particles to reversibly self-assemble into a vast collection of supracolloidal
      fullerene-like cages. We further elucidate the formation mechanisms of
      supracolloidal fullerene-like cages by analyzing the structural characteristics
      and the formation process. Our results provide conceptual and practical guidance
      towards the experimental realization of supracolloidal fullerene-like cages, as
      well as a new perspective on understanding the fullerene formation mechanisms.

PMID- 27874115
TI  - Magnetic fluorescent bifunctional spin-crossover complexes.
AB  - The rational design of magnetic and fluorescent bifunctional materials is
      attracting increasing interest. In this study, two mononuclear Fe(ii) complexes,
      namely [Fe(L)2(NCS)2] (1) and [Fe(L)2(NCSe)2] (2) are synthesised by combining a
      spin-crossover unit and a fluorescent ligand (naphth-1-yl)-N-(3,5-di(pyridin-2
      yl)-4H-1,2,4-triazol-4-yl)methanimine (L) to achieve bifunctionality. Single
      crystal X-ray studies and magnetic measurements confirm the presence of spin
      crossover behaviours; these measurements agree with the results of the
      temperature depended Raman spectra and infrared spectra. Thermally and light
      induced spin crossover is clearly observed for both complexes. The nature of the
      co-ligand (NCS-vs. NCSe-) shifts the transition temperature by approximately 60
      K. The infrared spectra after irradiation reveal that the electronic states are
      ascribable to the photomagnetic effect at 10 K. Furthermore, temperature
      dependent fluorescence emission spectra exhibit the coexistence of spin crossover
      and fluorescence for 1 and 2.

PMID- 27874116
TI  - Understanding carbohydrate-protein interactions using homologous supramolecular
      chiral Ru(ii)-glyconanoclusters.
AB  - Multivalent glycodendrimers make promising tools to tackle the basic and
      translational research in the field of carbohydrate-mediated interactions.
      Despite advances in glycodendrimers and glycopolymers, the multivalent probes
      available to date are still far from being ideal biological mimics. This work
      demonstrates the inherent chirality of glycodendrimers to be one of the promising
      factors to generate different spatial carbohydrate micro-environments to modulate
      specific carbohydrate-protein interactions. By exploiting the host-guest
      strategy, chiral Ru(ii) complexes (Delta and Lambda) and mannose capped beta
      cyclodextrin (beta-CD), we generated a library of homologous metallo
      glycodendrimers (MGDs) with sizes of 50-70 nm. These nanoclusters can
      enantioselectively bind to specific C-type lectins and displayed selectivity in
      cellular uptake. We also discovered their potential clathrin-mediated endocytotic
      pathway in DC-SIGN and SIGNR3-transfected cell lines. Finally, in vivo
      biodistribution and sequestration of MGDs was determined to understand the role
      of chirality mediated spatial arrangement in carbohydrate-mediated interactions.

PMID- 27874117
TI  - Quantitative analyses of enhanced thermoelectric properties of modulation-doped
      PEDOT:PSS/undoped Si (001) nanoscale heterostructures.
AB  - Poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) has high
      electrical conductivity (~103 S cm-1) but it exhibits a low Seebeck coefficient
      (<15 MUV K-1), resulting in a low power factor. Mixing PEDOT:PSS with
      nanostructured semiconductors can enhance the Seebeck coefficient and achieve an
      improved thermoelectric power factor. However, underlying mechanisms for those
      composite thermoelectric systems are scarcely understood so far. In this study,
      quantitative analyses on the electrical conductivity and Seebeck coefficient for
      the heterostructures of nanometer-thick PEDOT:PSS on single-crystal Si (001) on
      sapphire (SOS) are reported. The heterostructures have larger Seebeck
      coefficients up to 7.3 fold and power factors up to 17.5 fold relative to
      PEDOT:PSS. The electrical conductivity increased with decreasing combined
      thicknesses of PEDOT:PSS and Si, and the Seebeck coefficient increased with
      decreasing PEDOT:PSS thickness, which can be attributed to modulation doping
      caused by diffusion of holes from PEDOT:PSS into undoped Si. This hypothesis is
      supported by simulation per band alignment. The valence band offset between Si
      and PEDOT:PSS dominantly controls the electrical conductivity and Seebeck
      coefficient of the heterostructures. This study not only suggests mechanistic
      insights to increase the power factors of PEDOT:PSS-based composites but also
      opens the door for new strategies to enhance the thermoelectric efficiencies of
      heterostructured nanocomposite materials.

PMID- 27874118
TI  - The influence of temperature, pressure and Ag doping on the physical properties
      of TiO2 nanoceramics.
AB  - Undoped and Ag-doped TiO2 ceramics have been prepared at temperatures between 500
      1000  degrees C and under pressures up to 8 GPa. Their crystal structures and
      physical properties were investigated by means of EDX, SEM, TEM, X-ray powder
      diffraction, and magnetization M, specific heat Cp and electrical resistance rho
      measurements. It is found that the anatase-structured As-cast powder transforms
      into rutile and columbite-type at 500  degrees C and 5.5 GPa. The stabilization
      of the latter phase is fulfilled under a pressure of 8 GPa and at temperatures
      above 800  degrees C. On the basis of experimental results, we conclude that the
      physical properties of TiO2 can be tailored along with its crystal structure. In
      particular, magnetic properties change from paramagnetic in anatase and rutile to
      magnetic correlations and in all likelihood magnetic-field-induced
      antiferromagnetic short-range order in columbite-structured TiO2. Contrasting
      behaviour in the temperature dependences of specific heat between anatase/rutile
      and columbite-type TiO2 is obvious. Differently from anatase/rutile, the Cp of
      columbite-type TiO2 exhibits a low-temperature excess, being interpreted as due
      to magnetic correlations, or else the prevalence of soft modes. An analysis of
      rho(T) for columbite-type TiO2 in the temperature range of 280-400 K reveals the
      presence of a new trapping state at an energy level of ~28 meV within the
      originally forbidden gap. Furthermore, thermal fluctuation-induced tunnelling and
      hopping conductivities are suggested to govern in a lower temperature range. We
      recognize that the Ag-doped contents do not alter the crystal structure but
      considerably enhance magnetic correlations, compared to undoped samples.

PMID- 27874119
TI  - 99mTc-conjugated manganese-based mesoporous silica nanoparticles for SPECT, pH
      responsive MRI and anti-cancer drug delivery.
AB  - In recent decades, hybrid imaging techniques that exploit the advantages of
      multiple imaging technologies have aroused extensive attention due to the
      deficiencies of single imaging modes. Along with the development of single photon
      emission computed tomography-magnetic resonance imaging (SPECT-MRI), it is
      currently necessary to develop a series of dual probes that can combine the
      outstanding sensitivity of SPECT with the high spatial resolution of MRI. Herein,
      the commonly used technetium-99 (99mTc) was labelled on the surface of manganese
      oxide-based mesoporous silica nanoparticles (MnOx-MSNs) for use in SPECT-MRI dual
      modal imaging. The radiolabelling yield was as high as 99.1 +/- 0.6%, and the r1
      value of the nanoprobes was able to reach 6.60 mM-1 s-1 due to the pH-responsive
      properties of the MnOx-MSNs. The high-performance SPECT-MRI dual-modal imaging
      was confirmed in vivo in tumour-bearing mice, which could also provide semi
      quantitative information for tumour detection. Importantly, these nanoprobes can
      deliver anti-cancer drugs in cancer therapy due to their unique mesoporous
      structures. Thus, nanotheranostics combining dual-modal imaging with anti-cancer
      therapeutic properties were achieved.

PMID- 27874121
TI  - Emissive CdTe/ZnO/GO quasi-core-shell-shell hybrid quantum dots for white light
      emitting diodes.
AB  - Colloidal quantum dots (QDs) have been extensively studied for optoelectronic and
      biological applications due to their unique physical and optical properties. In
      particular, among the optoelectronics applications, the white light emitting
      diode (WLED) has great potential in flat panel displays and solid-state lighting.
      Herein, we demonstrate a novel, facile, and efficient technique for the synthesis
      of CdTe/ZnO/GO quasi-core-shell-shell hybrid quantum dots containing the CdTe
      core with multi shells of ZnO and graphene oxide (GO) and fabrication of WQDLEDs.
      The CdTe/ZnO/GO quasi-core-shell-shell QDs have a unique strong photoluminescence
      (PL) peak at 624 nm related to the CdTe core and new weak peaks at 382, 404, 422,
      and 440 nm due to conjugation with ZnO and GO. Also, in the electroluminescence
      (EL), multiple emission peaks are observed, which can be correlated to the
      recombination process inside the CdTe core and also recombination of electrons in
      the lowest unoccupied molecular orbital (LUMO) and LUMO+2 of GO and holes in the
      valence band (VB) of ZnO. The QDLEDs show clear white color emission with a
      maximum luminance value of about 480 cd m-2 with Commission Internationale de
      l'Eclairage (CIE) color coordinates of (0.35, 0.28).

PMID- 27874122
TI  - Surface-induced symmetry reduction in molecular switching: asymmetric cis-trans
      switching of CH3S-Au-SCH3 on Au(111).
AB  - The cis-trans isomerization of CH3S-Au-SCH3 driven by the tip of the scanning
      tunneling microscope is investigated at 77 K. CH3S-Au-SCH3 anchored on the
      Au(111) surface with the S-Au-S axis parallel to the substrate functions as a
      molecular switch due to the flipping of the CH3 groups. The bonding between CH3S
      Au-SCH3 and Au(111) leads to asymmetric isomerization where one of the two methyl
      groups flips much more effectively than the other, despite the symmetry of CH3S
      Au-SCH3. Our findings suggest the possibility of constructing similar molecular
      switches that can be operated at room temperature and a potential route for fine
      tuning of molecular switches in future nanoscale electro-mechanical devices.

PMID- 27874123
TI  - Bacteria-derived fluorescent carbon dots for microbial live/dead differentiation.
AB  - Microbial viability assessment plays a key role in many areas such as pathogen
      detection, infectious disease treatment and antimicrobial drug development. Many
      conventional viability dyes (such as propidium iodide, PI) used for
      differentiating live/dead microbes suffer from notable cytotoxicity, poor
      photostability and are of high cost. Thus their applications for accurate
      microbial viability determination are limited. Herein, for the first time we
      report the successful synthesis of fluorescent carbon dots (CDs) from bacteria
      via one-step hydrothermal carbonization. Benefiting from their highly negative
      surface charge (the zeta potential is as high as around -42 mV) and suitable
      size, the CDs can selectively stain dead microbial cells (bacteria and fungi) but
      not live ones. Importantly, compared to the widely used commercial dye PI, the
      developed CDs possess many great advantages including low cytotoxicity,
      multicolor imaging ability, excellent photostability and high selectivity.
      Moreover, because the synthetic method is simple, inexpensive and eco-friendly,
      this type of CD is suitable for large-scale production, making it an excellent
      candidate for microbial live/dead differentiation and viability assessment. The
      present work explores the feasibility of using bacteria to fabricate novel CDs
      and broadens the applications of CDs for biomedical applications.

PMID- 27874124
TI  - alpha-Fe2O3/TiO2 3D hierarchical nanostructures for enhanced photoelectrochemical
      water splitting.
AB  - We report the fabrication of 3D hierarchical hetero-nanostructures composed of
      thin alpha-Fe2O3 nanoflakes branched on TiO2 nanotubes. The novel alpha
      Fe2O3/TiO2 hierarchical nanostructures, synthesized on FTO through a multi-step
      hydrothermal process, exhibit enhanced performances in photo-electrochemical
      water splitting and in the photocatalytic degradation of an organic dye, with
      respect to pure TiO2 nanotubes. An enhanced separation of photogenerated charge
      carriers is here proposed as the main factor for the observed photo-activities:
      electrons photogenerated in TiO2 are efficiently collected at FTO, while holes
      are transferred to the alpha-Fe2O3 nanobranches that serve as charge mediators to
      the electrolyte. The morphology of alpha-Fe2O3 that varies from ultrathin
      nanoflakes to nanorod/nanofiber structures depending on the Fe precursor
      concentration was shown to have a significant impact on the photo-induced
      activity of the alpha-Fe2O3/TiO2 composites. In particular, it is shown that for
      an optimized photo-electrochemical structure, a combination of critical factors
      should be achieved such as (i) TiO2 light absorption and photo-activation
      vs.alpha-Fe2O3-induced shadowing effect and (ii) the availability of free TiO2
      surface vs.alpha-Fe2O3-coated surface. Finally, theoretical analysis, based on
      DFT calculations, confirmed the optical properties experimentally determined for
      the alpha-Fe2O3/TiO2 hierarchical nanostructures. We anticipate that this new
      multi-step hydrothermal process can be a blueprint for the design and development
      of other hierarchical heterogeneous metal oxide electrodes suitable for photo
      electrochemical applications.

PMID- 27874127
TI  - Enhanced CO oxidation on CeO2/Co3O4 nanojunctions derived from annealing of metal
      organic frameworks.
AB  - The interface of nanojunctions plays an important role in the performance of
      heterogeneous catalysts. However, it is highly challenging to construct
      nanojunctions which are usually prepared by complex multistep processes. Metal
      organic frameworks (MOFs), with designable metal centers and tunable organic
      ligands, are promising precursors for the one-step synthesis of nanojunctions.
      Herein, we prepared porous CeO2/Co3O4 nanojunctions by direct annealing of MOFs
      in air. These unique nanojunctions exhibit remarkable catalytic activity for CO
      oxidation, which can achieve complete oxidization of CO to CO2 at 110  degrees C.
      In contrast, the temperature required for 100% CO oxidation is 190  degrees C for
      pure Co3O4. Moreover, the nanojunctions can maintain complete CO conversion after
      16 h at 110  degrees C. Density functional theory calculations revealed that the
      enhancement in the catalytic activity of CeO2/Co3O4 nanojunctions can be
      attributed to the charge transfer through the interfaces of the nanojunctions.

PMID- 27874128
TI  - Boron distributions in individual core-shell Ge/Si and Si/Ge heterostructured
      nanowires.
AB  - Ge/Si and Si/Ge core-shell nanowires (NWs) have substantial potential for
      application in many kinds of devices. Because impurity distributions in Ge/Si and
      Si/Ge core-shell NWs strongly affect their electrical properties, which in turn
      affect device performance, this issue needs urgent attention. Here we report an
      atom probe tomographic study of the distribution of boron (B), one of the most
      important impurities, in two kinds of NWs. B atoms were doped into the Si regions
      of Ge/Si and Si/Ge core-shell NWs. It was found that the B atoms were randomly
      distributed in the Si shell of the Ge/Si core-shell NWs. In the Si/Ge core-shell
      NWs, on the other hand, the B distributions depended on the growth temperature
      and the B2H6 flux. With a higher growth temperature and an increased B2H6 flux,
      the B atoms piled up in the outer region of the Si core. However, the B atoms
      were observed to be randomly distributed in the Si core after decreasing both the
      growth temperature and the B2H6 flux.

PMID- 27874129
TI  - Binding of human serum albumin to PEGylated liposomes: insights into binding
      numbers and dynamics by fluorescence correlation spectroscopy.
AB  - Liposomes for medical applications are often administered by intravenous
      injection. Once in the bloodstream, the liposomes are covered with a "protein
      corona", which impacts the behavior and eventual fate of the liposomes.
      Currently, many aspects of the liposomal protein corona are not well understood.
      For example, there is generally a lack of knowledge about the liposome binding
      affinities and dynamics of common types of blood plasma proteins. Fluorescence
      correlation spectroscopy (FCS) is a powerful experimental technique that
      potentially can provide such knowledge. In this study, we have used FCS to
      investigate the binding of human serum albumin (HSA) to standard types of
      PEGylated fluid-phase liposomes (consisting of DOPC and DOPE-PEG2k) and PEGylated
      gel-phase liposomes (consisting of DSPC and DSPE-PEG2k) with various PEG chain
      surface densities. We detected no significant binding of HSA to the PEGylated
      fluid-phase liposomes. In contrast, we found that HSA bound tightly to the
      PEGylated gel-phase liposomes, although only a low number of HSA molecules could
      be accommodated per liposome. Overall, we believe that our data provides a useful
      benchmark for other researchers interested in studying the liposomal protein
      corona.

PMID- 27874130
TI  - Enhanced performance of perovskite solar cells by modulating the Lewis acid-base
      reaction.
AB  - The Lewis acid-base reaction between PbI2 and solvent molecules is popular in
      fabricating PbI2 films by a two-step method for making perovskite solar cells.
      Here, we control the microstructure of PbI2 films through modulating the Lewis
      acid-base reaction by adding a small amount of N-methyl pyrrolidone into PbI2/DMF
      solution. PbI2 films with excellent crystallinity and full coverage are
      fabricated by spin-coating the mixed solution on the substrate, which leads to
      high quality perovskite layers with low recombination rate and high efficiency
      for carrier transfer. As a result, the power conversion efficiency of the best
      perovskite solar cells increases from 13.3% to 17.5%.

PMID- 27874132
TI  - Cubic mesoporous Ag@CN: a high performance humidity sensor.
AB  - The fabrication of highly responsive, rapid response/recovery and durable
      relative humidity (%RH) sensors that can precisely monitor humidity levels still
      remains a considerable challenge for realizing the next generation humidity
      sensing applications. Herein, we report a remarkably sensitive and rapid %RH
      sensor having a reversible response using a nanocasting route for synthesizing
      mesoporous g-CN (commonly known as g-C3N4). The 3D replicated cubic mesostructure
      provides a high surface area thereby increasing the adsorption, transmission of
      charge carriers and desorption of water molecules across the sensor surfaces.
      Owing to its unique structure, the mesoporous g-CN functionalized with well
      dispersed catalytic Ag nanoparticles exhibits excellent sensitivity in the 11-98%
      RH range while retaining high stability, negligible hysteresis and superior real
      time %RH detection performances. Compared to conventional resistive sensors based
      on metal oxides, a rapid response time (3 s) and recovery time (1.4 s) were
      observed in the 11-98% RH range. Such impressive features originate from the
      planar morphology of g-CN as well as unique physical affinity and favourable
      electronic band positions of this material that facilitate water adsorption and
      charge transportation. Mesoporous g-CN with Ag nanoparticles is demonstrated to
      provide an effective strategy in designing high performance %RH sensors and show
      great promise for utilization of mesoporous 2D layered materials in the Internet
      of Things and next generation humidity sensing applications.

PMID- 27874134
TI  - Visible-light-induced phenylchalcogenyl-oxygenation of allenes having aryl or
      electron withdrawing substituents with ambient air as a sole oxidant.
AB  - The synthesis of regio- and stereoselective aryl substituted alpha,beta
      unsaturated aldehydes and ketones from activated allenes was achieved. This mild
      and non-metallic oxidation is exclusively driven by benign ambient air and
      triggered by visible light. The same starting materials under ideal anaerobic
      conditions led to the 2,3-diphenylselenation adduct with no trace of oxygenated
      products, demonstrating dissolved oxygen as a chemical switch for two different
      reaction pathways. The salient feature of this protocol is the single electron
      transfer (SET) achieved by irradiation of one of two organic molecules thereby
      avoiding a sensitizer to form a radical ion pair.

PMID- 27874133
TI  - The structural and electronic properties of NbSin-/0 (n = 3-12) clusters: anion
      photoelectron spectroscopy and ab initio calculations.
AB  - Niobium-doped silicon clusters, NbSin- (n = 3-12), were generated by laser
      vaporization and investigated by anion photoelectron spectroscopy. The structures
      and electronic properties of NbSin- anions and their neutral counterparts were
      investigated with ab initio calculations and compared with the experimental
      results. It is found that the Nb atom in NbSin-/0 prefers to occupy the high
      coordination sites to form more Nb-Si bonds. The most stable structures of NbSi3
      7-/0 are all exohedral structures with the Nb atom face-capping the Sin
      frameworks. At n = 8, both the anion and neutral adopt a boat-shaped structure
      and the openings of the boat-shaped structures remain unclosed in NbSi9-10-/0
      clusters. The most stable structure of the NbSi11- anion is endohedral, while
      that of neutral NbSi11 is exohedral. The global minima of both the NbSi12- anion
      and neutral NbSi12 are D6h symmetric hexagonal prisms with the Nb atom at the
      center. The perfect D6h symmetric hexagonal prism of NbSi12- is electronically
      stable as it obeys the 18-electron rule and has a shell-closed electronic
      structure with a large HOMO-LUMO gap of 2.70 eV. The molecular orbital analysis
      of NbSi12- suggests that the delocalized Nb-Si12 ligand interactions may
      contribute to the stability of the D6h symmetric hexagonal prism. The AdNDP
      analysis shows that the delocalized 2c-2e Si-Si bonds and multicenter-2e NbSin
      bonds are important for the structural stability of the NbSi12- anion.

PMID- 27874135
TI  - Correction: Characteristics and reactivity of ruthenium-oxo complexes.
AB  - Correction for 'Characteristics and reactivity of ruthenium-oxo complexes' by
      Tomoya Ishizuka et al., Dalton Trans., 2016, 45, 16727-16750.

PMID- 27874136
TI  - A self-quenching-resistant carbon nanodot powder with multicolored solid-state
      fluorescence for ultra-fast staining of various representative bacterial species
      within one minute.
AB  - In this study, we prepared self-quenching-resistant solid-state fluorescent
      carbon nanodots (SFCDs) without any other solid matrices. The SFCDs were prepared
      using a one-step microwave synthesis method through precise control of the
      heating power and time. The resulting SFCD powder showed excitation-dependent
      emission behavior with a maximum fluorescence quantum yield of 40%. The
      multicolored SFCDs were successfully used as fluorescent agents for rapid
      staining of 14 representative bacterial species, including Gram-negative, Gram
      positive, and acid-fast bacteria. Moreover, some pathogenic bacteria, including
      Bacillus anthracis (vegetative cells and endospores), Yersinia pestis, Vibrio
      cholera O1, Listeria monocytogenes, Neisseria meningitidis, and Klebsiella
      pneumoniae, could all be stained within just 1 min by the smear staining method
      without any incubation, which was also applicable by using the liquid incubation
      method. Moreover, excellent staining quality, superior resistance to
      photobleaching, high stability in solutions of different pH values, and low
      toxicity were also demonstrated.

PMID- 27874138
TI  - Self-supported three-dimensional mesoporous semimetallic WP2 nanowire arrays on
      carbon cloth as a flexible cathode for efficient hydrogen evolution.
AB  - The design and development of high-efficiency and non-noble metal hydrogen
      evolution reaction (HER) electrocatalysts with optimized nanostructures for human
      clean and sustainable energy systems has attracted significant research interest
      over the past years. Herein, self-supported semimetallic tungsten diphosphide
      nanowire arrays on carbon cloth (WP2 NWs/CC) were topotactically fabricated by in
      situ phosphidation of a WO3 NWs/CC precursor. Such a binder-free flexible HER
      cathode with integrated three-dimensional nanostructures can not only provide a
      large surface area to expose abundant active sites, but also facilitate
      electrolyte penetration for electrons and electrolyte ions. The WP2 NWs/CC
      electrode exhibits superior catalytic performance, and it needs overpotentials of
      109 and 160 mV with a small Tafel slope of 56 mV dec-1 to achieve current
      densities of 10 and 50 mA cm-2, respectively. High stability in acidic media is
      also observed for the catalyst for a duration of 20 hours at least. In addition,
      density functional theory (DFT) calculations indicate a low kinetic energy
      barrier for H atom adsorption on the WP2 surface which guarantees the excellent
      catalytic activity of the catalyst, and the influences of phosphidation
      temperature on the HER activity are also studied. The excellent electrocatalytic
      activity makes the present 3D structured WP2 NWs/CC a promising catalyst for
      large scale highly pure hydrogen evolution by electrochemical water splitting.

PMID- 27874139
TI  - The origin of facet selectivity and alignment in anatase TiO2 nanoparticles in
      electrolyte solutions: implications for oriented attachment in metal oxides.
AB  - Oriented attachment (OA) is an important nonclassical pathway for crystal growth
      from solution, occurring by the self-assembly of nanoparticles and often leading
      to highly organized three-dimensional crystal morphologies. The forces that drive
      nanocrystal reorientation for face-selective attachment and exclude improperly
      aligned particles have remained unknown. Here we report evidence at the
      microscopic level that ion correlation forces arising from dynamically
      interacting electrical double layers are responsible for face-selective
      attraction and particle rotation into lattice co-alignment as particles interact
      at long range. Atomic-to-mesoscale simulations developed and performed for the
      archetype OA system of anatase TiO2 nanoparticles in aqueous HCl solutions show
      that face-selective attraction from ion correlation forces outcompetes
      electrostatic repulsion at several nanometers apart, drawing particle face pairs
      into a metastable solvent-separated captured state. The analysis of the facet and
      pH dependence of interparticle interactions is in quantitative agreement with the
      observed decreasing frequency of attachment between the (112), (001), and (101)
      face pairs, revealing an adhesion barrier that is largely due to steric hydration
      forces from structured intervening solvents. This finding helps open new avenues
      for controlling crystal growth pathways leading to highly ordered three
      dimensional nanomaterials.

PMID- 27874140
TI  - Carbon nanotube fibers and films: synthesis, applications and perspectives of the
      direct-spinning method.
AB  - The direct-spinning method of creation of CNT macroassemblies has received a lot
      of attention because of its simplicity to produce high-performance material
      without apparent limits to its size. CNT fibers or films have shown unparalleled
      properties and opened new areas of research and commercial development. The
      process designed more than a decade ago has already given interesting information
      about the basic science of nanomaterials, which in parallel led to the creation
      of the first prototypes with high potential of implementation in everyday life.
      Because of this, there has been growing interest in this technique with research
      articles coming into view from all around the world on a frequent basis. This
      review aims to summarize all the progress made in the direct-spinning process on
      a spectrum of fronts ranging from the study of complex synthesis parameters,
      material properties to its viable applications. The strong and weak points of the
      "Cambridge process" are carefully evaluated to put forward what challenges are
      most pressing. The future overlook puts the state of the art into perspective and
      suggests the prospective research directions.

PMID- 27874141
TI  - Halogen bonding rotaxanes for nitrate recognition in aqueous media.
AB  - Targeting the biologically and environmentally important nitrate anion, halogen
      bonding (XB) has been incorporated into three novel [2]rotaxane structural
      frameworks via an axle component containing covalently linked 3,5-bis
      iodotriazole pyridine-pyridinium motifs. This has enabled the recognition of
      nitrate in aqueous media containing up to 90% water with equivalent binding
      affinity to chloride, illustrating the potency of XB for anion recognition in
      highly competitive aqueous solvent mixtures.

PMID- 27874142
TI  - Designed synthesis of MOx (M = Zn, Fe, Sn, Ni, Mn, Co, Ce, Mg, Ag), Pt, and Au
      nanoparticles supported on hierarchical CuO hollow structures.
AB  - Despite intensive research into support substrates for the dispersal of
      nanoparticles and their applications, there has been a lack of general methods to
      produce metal oxide hollow substrates supporting a wide range of metal and metal
      oxides. Herein, a synthetic protocol for the preparation of CuO hollow structure
      supported MOx (M = Zn, Fe, Ni, Sn, Mn, Co, Ce, Mg, and Ag) and noble metals (Pt
      and Au) with the desired properties and shell structure, such as CuO/Fe2O3,
      CuO/ZnO, CuO/SnO2, CuO/MgO, CuO/NiO, CuO/Mn2O3, CuO/CoO, CuO/CeO2, CuO/Ag2O,
      CuO/Pt, CuO/Au hollow cubes, CuO/ZnO double-shell hollow cubes, CuO/SnO2 double
      shell hollow octahedra, CuO/SnO2/Fe2O3 and CuO/Mn2O3/NiO double-shell hollow
      cubes, was developed based on controlled calcination and etching. These hybrid
      hollow structures were employed not only as support substrates but also as active
      constituents for catalytic reactions. As an example, we demonstrated that CuO/ZnO
      hollow cubes are remarkably efficient in converting solid chitin biomass to
      liquid chemicals in methanol. In addition, CuO/ZnO double-shell hollow cubes were
      highly effective in the oxidation of benzyl alcohol in the presence of H2O2,
      whereas CuO/Pt and CuO/Au hollow cubes promoted the oxidation of benzyl alcohol
      in pure O2. The strategy developed in this work extends the controllable
      fabrication of high-quality CuO hollow structure-supported nanoparticles using
      various compositions and shell structures, paving the way to the exploration and
      systematic comparison of these materials in a wider range of applications.

PMID- 27874143
TI  - Total synthesis of natural derivatives and artificial analogs of 13-oxyingenol
      and their biological evaluation.
AB  - We have established an efficient synthetic methodology for the 13-oxyingenol
      natural derivative (13-oxyingenol-13-dodecanoate-20-hexanoate), featuring a ring
      closing olefin metathesis reaction for the "direct" construction of a highly
      strained inside-outside framework and a Mislow-Evans-type [2,3]-sigmatropic
      rearrangement for the stereoselective introduction of the hydroxy group at C5. We
      also synthesized artificial analogs of 13-oxyingenol and ingenol by using our
      synthetic strategy. In vitro activation assays of protein kinase C (PKC) alpha
      and delta revealed that the dodecanoyl group at O13 on 13-oxyingenol analogs had
      a significant role in PKCdelta activation. The PKCalpha- or PKCdelta-activating
      13-oxyingenol and ingenol analogs induced both distinct morphological changes and
      increases of CD11b expression in HL-60 cells, which would be typical signs of HL
      60 cell differentiation to macrophage-like cells, as expected by previous
      reports. Intriguingly, however, similar differentiation phenotypes were observed
      with the use of 13-oxyingenol natural derivatives and 13-oxyingenol-13
      dodecanoate showing a remarkably less potent PKCalpha or PKCdelta activation
      ability, which the PKC inhibitor Go6983 diminished. This indicated the
      involvement of other PKC isozymes or related kinase activities. 13-Oxyingenol
      analogs, which induced HL-60 cell differentiation, also induced HL-60 cell death,
      similar to the action of a phorbol ester, a strong PKC activator.

PMID- 27874144
TI  - A novel photosensitizer: An l-glutamide lipid conjugate with improved properties
      for photodynamic therapy.
AB  - Photosensitizers (PS) are used in photodynamic therapy to treat several cancers.
      The efficacy of photodynamic therapy (PDT) could be further improved by
      overcoming aggregation-dependent quenching of PS and by improving the
      biodistribution of the PS. In this work we attempted to overcome these issues by
      conjugating a PS with a lipid molecule and tested the liposomes prepared with
      this PS conjugated lipid for PDT. A novel lipid-porphyrin conjugate (1 : 1) was
      synthesized by attaching a PS, 5-(4-methoxycarbonylphenyl)-10,15,20-triphenyl
      21H,23H-porphine, to the head group of a glutamide lipid. Two liposomal
      preparations, with egg phosphatidylcholine as the bulk lipid, were prepared viz.
      liposomes with PS conjugated lipid (LPSL) and PS entrapped in liposomes (PSL). At
      equimolar concentrations of the PS, both liposomal preparations were found to
      generate comparable amounts of reactive oxygen species as free PS upon light
      exposure. Electron micrographs and dynamic light scattering measurements
      indicated uniform and circular liposomes of 150 nm in size and near neutral zeta
      potential. Uptake of these liposomes by the human ovarian carcinoma cell line, SK
      OV-3, was shown by FACS and confocal microscopy. Upon light exposure, the LPSL,
      i.e., with the conjugate lipid, have shown a substantial decrease (>4 times) in
      the PS requirement compared to PSL or free PS in its ability to cause light
      mediated cell death of SK-OV-3 cells. The light mediate cell death by LPSL was
      shown to be not dependent on the bulk properties of the lipid. Our data suggest a
      potential benefit of conjugating PS with a lipid in improving the efficiency of
      PDT.

PMID- 27874145
TI  - Personalized medicine. Is it time for infectious diseases?
AB  - [No Abstract Available].

PMID- 27874146
TI  - Roles of nucleolin. Focus on cancer and anti-cancer therapy.
AB  - Nucleolin, a multifunctional protein distributed in the nucleolus, participates
      in many modulations including rDNA transcription, RNA metabolism, and ribosome
      assembly. Nucleolin is also found in the cytoplasm and on the cell membrane, and
      surface nucleolin can bind to various ligands to affect many physiological
      functions. The expression and localization of nucleolin is often abnormal in
      cancers, as the differential distribution of nucleolin in cancer can influence
      the carcinogenesis, proliferation, survival, and metastasis of cancer cells,
      leading to the cancer progression. Thus, nucleolin may be a novel and promising
      target for anti-cancer treatment. Here, we describe how nucleolin act functions
      in cancer development and describe nucleolin-dependent anti-cancer therapies.

PMID- 27874147
TI  - Open globe eye injury characteristics and prognostic factors in Jazan, Saudi
      Arabia.
AB  - OBJECTIVES: To evaluate characteristics and prognostic factors of open globe
      injuries (OGI) presented to King Fahad Specialist Hospital in the Jazan region,
      Saudi Arabia.  Methods: This study is a retrospective review of medical records
      of OGI patients who underwent operative repair of their injuries in King Fahad
      Central Hospital, Jazan, Saudi Arabia between January 2011 and December 2013.
      Demographic information, eye injury, preoperative, and postoperative visual
      acuity were collected. The initial and final visual acuity outcomes were compared
      to identify subjects who witnessed any improvement in their visual acuity.
      Logistic regression was used to assess characteristics associated with
      improvements in the visual acuity.  Results: Number of included cases was 120.
      Most frequently reported causes of injury were blunt trauma (20%) and shattered
      glass (18.3%). Approximately half of the cases were reported to have iris
      injuries or hyphema. Most cases suffered penetration (37.5%) of the eye globe.
      Only zone I injury was significantly associated with better visual acuity
      outcomes (odds ratio [OR]: 2.447, p=0.036). Among the variables that were
      associated with poorer prognostic outcomes, only aphakia (OR: 0.180), retinal
      damage (OR: 0.062), vitreous hemorrhage (OR: 0.266), and zone III injuries (OR:
      0.092) were statistically significant (p less than 0.05).     Conclusion: Zone I
      injury appears to have a better prognostic effect on visual acuity where injuries
      related to Zone III were associated with worse prognostic outcomes.

PMID- 27874148
TI  - Dry eye disease in patients with metabolic syndrome.
AB  - OBJECTIVES: To evaluate dry eye disease (DED) in patients with metabolic syndrome
      (MetS) and compare with healthy individuals. METHODS: The study was conducted in
      the Ophthalmology and Endocrinology Department of Bagcilar Education and Research
      Hospital, a tertiary care center in Istanbul, Turkey, between January and
      December 2015. In this prospective case-controlled study, dry eye disease tests
      were performed on 44 patients with MetS and 43 healthy controls. TearLab
      Osmolarity System, which is a lab-on-a-chip technology, was used to measure tear
      osmolarity. McMonnies & Ho symptoms questionnaire along with Schirmer I test and
      tear film break-up time (TFBUT) test were also performed. Statistical evaluation
      was performed by students' independent test. RESULTS: There was no statistically
      significant difference in tear osmolarity, TFBUT, and McMonnies and Ho
      questionnaire scores between MetS and normal group. However, Schirmer I test was
      significantly higher in MetS group (14.8+/-9.4mm versus 20.4+/-9.4, p=0.007). In
      women subgroup, tear osmolarity was significantly higher in MetS group compared 
      to the normal group and over the cut-off score 308 mOsm/L (309.4+/-13.1 mOsm/L
      versus 301.2+/-8.7mOsm/L, p=0.012). CONCLUSION: Patients with MetS present with
      lower tear volumes and a higher incidence of lacrimal gland hypofunction than age
      matched controls. Especially women with MetS have higher tear osmolarities, which
      disrupt the normal functioning of the ocular surface and cause inflammation.
      Clinicians should be aware of higher DED incidence in patients with MetS for
      early treatment to prevent serious ocular complications.

PMID- 27874149
TI  - Gastroesophageal stenting for the management of post sleeve gastrectomy leak. A
      single institution experience.
AB  - OBJECTIVES: To retrospectively evaluate the effectiveness of gastroesophageal
      stenting for post sleeve gastrectomy staple line leaks using removable self
      expandable stents. METHODS: Between April 2012 and June 2015, 12 consecutive
      patients (6 males) with mean age of 34 years (21-38 years) presented with staple
      line leak 1-8 weeks after the operation (mean 2.8 weeks). Patients underwent
      gastroesophageal stenting by interventional radiology. A total of 23 stents were
      deployed with mean length of 17.8 cm (7-24 cm) and mean diameter 25.6 mm (18-36
      mm). Stent re-insertion was needed in 7 patients (9 procedure), while 6 patients
      required percutaneous collection drainage and 3 patients required endoscopic glue
      injection with clipping. Two stent removal procedures were carried out under
      endoscopic visualization after failed stent capture under fluoroscopy, while the
      remaining stents were successfully removed by interventional radiology. Results:
      Stent placement was technically successful in all patients. Stent migration
      occurred in 6 patients (50%). There is a tendency for stent migration with
      shorter stent length (R= -0.557, p=0.008). The mean duration of stenting was 60.5
      days (14-137 days). All patients underwent stent removal and resumed oral intake
      with no recurrence of leak at a mean follow up time of 190 days (14-410 days).
      Complications included gastrointestinal bleeding (n=1), proximal esophageal
      stricture (n=1) and stent occlusion (n=1). CONCLUSION: Gastroesophageal stenting
      as a primary measure after diagnosis of early post sleeve gastrectomy leak
      appears to offer a safe and effective alternative option in obviating repeat
      surgical interventions. Minimally invasive interventions may still be required
      for the management of persistent leak.

PMID- 27874150
TI  - The radiological research for pelvis asymmetry of unilateral developmental
      dysplasia of the hip in adult.
AB  - OBJECTIVES: To investigate whether adult patients with unilateral developmental
      dysplasia of the hip (UDDH) have pelvic asymmetry and what correlation existing
      between them. Methods: A total of 100 adult patients with UDDH were enrolled in
      the retrospective observational study in Shanghai Jiaotong University Affiliated
      Sixth People's Hospital, Shanghai, China, between January 2012 and February 2014.
      The anteroposterior pelvic radiographs were reviewed and the pelvic heights and
      ischium heights were measured and compared between the affected and non-affected
      sides to find out the relationship between the pelvic morphology and hip
      dysplasia. Results: The pelvic heights demonstrated significant differences
      between the non-affected side and the affected side in patients with Crowe type
      II-IV UDDH (p less than 0.05), but not in patients with Crowe type I UDDH
      (p=0.09). There were significant differences in the bilateral ischium heights in
      patients with Crowe type III and IV UDDH (p less than 0.05), but not in patients
      with Crowe type I and II UDDH (p=0.78, p=0.055). In addition, the degree of hip
      dysplasia was positively associated with the degrees of asymmetry of pelvis
      (r=0.78, p less than 0.001) and ischium (r=0.72, p less than 0.001) in UDDH
      patients. Conclusion: The pelvic asymmetry exists in adult patients with UDDH. In
      addition, the degree of asymmetry has correlation with the degree of hip
      dysplasia. We recommend that it should be taken more cautions to use teardrops
      and ischial tuberosity as anatomy landmarks to balance leg-length discrepancy for
      unilateral DDH patients in preoperative planning and total hip arthroplasty.

PMID- 27874151
TI  - A stepwise introduction of a successful antimicrobial stewardship program.
      Experience from a tertiary care university hospital in Western, Saudi Arabia.
AB  - OBJECTIVES: To analyze and evaluate the safety and cost-effectiveness of a
      gradually-implemented antimicrobial stewardship programs (ASP) in a tertiary care
      center. METHODS: Prospective data were collected from an ASP that was gradually
      introduced between April 2012 and December 2013 in 6 hospital departments, over
      successive periods of 3 months each. A multidisciplinary team supervised
      antibiotic use and regulated pharmacy dispensations of a list of restricted
      antimicrobials (RAs). Indicators were prospectively monitored and included
      hospital mortality as the safety indicator; incidence of multi-drug resistance
      (MDR) infections as the effectiveness indicator, RA cost savings as the cost
      effectiveness indicator and RA consumption indicated the process implementation.
      RESULTS: Between 2012 and 2014, dispensations of RAs decreased by 67% and
      prescriptions by 75%; no increase in mortality rate was observed.
      Microbiologically, there was a decreasing trend of incidence across all monitored
      infections, but this was only significant for Acinetobacter baumannii (p=0.007).
      Cost analysis showed a decrease in expenditure for RAs, with an average monthly
      saving of up to 326,020USD. CONCLUSIONS: Stepwise implementation of ASPs is a
      safe and cost-effective strategy for improving antibiotic prescribing practice
      and to reduce multi-drug resistance.

PMID- 27874152
TI  - Healthcare professionals' awareness and knowledge of adverse drug reactions and
      pharmacovigilance.
AB  - OBJECTIVES: To document the knowledge of, attitudes toward, and practices of
      adverse drug reaction (ADR) reporting and pharmacovigilance systems among
      healthcare professionals. Methods: This descriptive cross-sectional study was
      conducted using a questionnaire. This study took place at King Fahd Hospital of
      the University (KFHU), Khobar, Kingdom of Saudi Arabia,  between  April 2015 and 
      April 2016. Healthcare professionals, including physicians, pharmacists, pharmacy
      technicians, and nurses, were considered eligible and invited to take part in the
      study. A link to the online questionnaire was sent to each participant via E
      mail, and a hard copy was circulated at the hospital after the objectives of the
      study were explained. The questionnaire comprised items regarding
      knowledge/awareness of pharmacovigilance and ADRs, perception/attitude towards
      pharmacovigilance and ADR reporting, and practices of ADR reporting. Descriptive
      statistics were used to analyze the data. Results: A total of 400 questionnaires
      were distributed to the healthcare professionals and 331 participants responded,
      providing a response rate of 82.75%. The healthcare professionals comprised 161
      physicians, 39 pharmacists, 21 pharmacist technicians, and 110 nurses. Most of
      the participants were female (n=198) and Saudi (61.9%). Most healthcare
      professionals (62.5%) were unaware of the term pharmacovigilance; the pharmacists
      and pharmacist technicians had the highest rate of pharmacovigilance awareness
      (60.5% of the pharmacists and 40% of pharmacist technicians). Conclusion: There
      is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among
      healthcare professionals working at KFHU.

PMID- 27874153
TI  - Effects of personality traits on collaborative performance in problem-based
      learning tutorials.
AB  - OBJECTIVES: To examine the relationship between students' collaborative
      performance in a problem-based learning (PBL) environment and their personality
      traits. Methods:This retrospective, cross-sectional study was conducted using
      student data of a PBL program between 2013 and 2014 at Sungkyunkwan University
      School of Medicine, Seoul, South Korea. Eighty students were included in the
      study. Student data from the Temperament and Character Inventory were used as a
      measure of their personality traits. Peer evaluation scores during PBL were used
      as a measure of students' collaborative performance. Results: Simple regression
      analyses indicated that participation was negatively related to harm avoidance
      and positively related to persistence, whereas preparedness for the group work
      was negatively related to reward dependence. On multiple regression analyses, low
      reward dependence remained a significant predictor of preparedness. Grade-point
      average (GPA)  was negatively associated with novelty seeking and cooperativeness
      and was positively associated with persistence.  Conclusion: Medical students who
      are less dependent on social reward are more likely to complete assigned
      independent work to prepare for the PBL tutorials. The findings of this study can
      help educators better understand and support medical students who are at risk of
      struggling in collaborative learning environments.

PMID- 27874154
TI  - Characterizing sleeping habits and disturbances among Saudi adults.
AB  - OBJECTIVES: To characterize sleeping habits, assess sleep disturbance prevalence,
      and identify associated factors among Saudi adults.  Methods: A total of 1720
      adults were approached for this observational cross-sectional study between
      October 2014 and March 2015. The study took place in Riyadh, the capital of Saudi
      Arabia. We used a questionnaire to describe sleeping characteristics in relation
      to existing chronic diseases, smoking status, obesity, daily performance and
      sociodemographic variables. Results: The response rate was 79.6% (1369
      participants), 61.6% have or may have sleeping disturbances of which 18.6%
      claimed either slowed or stopped breathing during sleep. Women reported a higher
      prevalence of sleep disturbances (65.2%). Feeling tired was significantly
      associated with sleep disturbance (49% versus 19.7%) (p greater than 0.001).
      Approximately 78.4% of those with sleep disturbance significantly believed that
      their ability to perform daily tasks is affected (p=0.005). Moreover, smoking and
      obesity were significantly associated with sleep disturbances (p less than 0.01).
      Participants with asthma, hypertension, chronic heart disease, and diabetes
      mellitus reported significantly more sleeping disturbance (p=0.016 to p=0.001).
      Conclusions: Sleep disturbances are associated with obesity, smoking, chronic
      health conditions, and lower performance among  Saudi adults.

PMID- 27874155
TI  - Phase down of amalgam. Awareness of Minamata convention among Jordanian dentists.
AB  - OBJECTIVES: To assess the knowledge of Jordanian dentists toward phase down of
      dental amalgam as recommended by the Minamata Convention, and their training and
      competency in placing posterior composites.  Methods: This study was conducted
      through structured questionnaire interviews with randomly selected cohort of
      dentists in Jordan between March 2015 and June 2015. Out of 230 dentists who were
      invited, 196 (85.2%) agreed to participate. Dentists were asked if they know
      about the Minamata Convention. They were also asked about their training in
      placement of posterior composite.  Results: Out of the 196 interviewed, only
      13.8% know about Minamata Convention and 17% had an undergraduate training in
      favor of placing composites in posterior teeth. Approximately 50% of those
      dentists were not trained in using rubber dam when placing posterior composites,
      while only 38.3% had training in sectional matrix placement. Undergraduate
      training did not influence (p=0.00) the dentists' decision to remove old amalgam
      based on patient's demands. Only 28.1% were of the opinion of discontinuing the
      use of amalgam due to its alleged health and environmental hazards. There was no
      general agreement on the type of composite, liner, and bonding strategy when
      placing posterior composites. Conclusion: Dentists are not well informed on the
      Minamata Convention and the phase down of amalgam. Training in posterior
      composite placement should be given more room in undergraduate curriculum and
      continuous dental education.

PMID- 27874157
TI  - Excision of oral pyogenic granuloma in a diabetic patient with 940nm diode laser.
AB  - Pyogenic granuloma (PG) is a common, acquired, benign vascular reactive
      proliferation that typically develops as a small erythematous papule on the skin
      or oral mucosal surface. Oral PG is often caused by constant low-grade infection,
      minor trauma, poor oral hygiene, and due to hormonal disturbances. It shows a
      striking predilection for the gingiva. Lesions can be excised surgically with
      removal of the underlying causes. However, this modality may be associated with
      unnecessary complications. Recently, different laser wavelengths have been used
      for removal of oral PG. Herein, we present a case of gingival PG in a 51-year-old
      uncontrolled diabetic woman. The lesion was excised successfully with a 940nm
      diode laser as a conservative and non-stressful procedure that resulted in a
      bloodless surgical and post-surgical course with rapid healing, minimal pain,
      swelling, and scarring. The 940nm Diode laser offers a new efficient noninvasive
      tool for excising oral soft tissue lesions, especially in medically compromised
      patients.

PMID- 27874156
TI  - Prevalence of obesity in elementary school children and its association with
      dental caries.
AB  - OBJECTIVES: To investigate the prevalence of obesity among elementary school
      children and to examine the association between obesity and caries activity in
      the mixed dentition stage. Methods: This cross-sectional study was conducted in
      King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia between September 2014
      and June 2015 using a multi-stage stratified sample of 915 elementary school
      children (482 boys, 433 girls) in Jeddah, Saudi Arabia. Anthropometric
      measurements, consisting of height, weight, body mass index (BMI), and waist
      circumference (WC), were obtained. Children were classified as
      underweight/healthy, overweight, or obese and as non-obese or obese according to
      their BMI and WC, respectively. Each child's caries experience was assessed using
      the decay score in the primary and permanent teeth. Results: Based on BMI, 18% of
      children were obese, 18% were overweight, and 64% were underweight/normal. Based
      on WC, 16% of children were obese, and 84% were non-obese. Girls had a
      significantly higher prevalence of obesity based on WC measurements (p less than
      0.001), but not BMI. Children enrolled in private schools had a significantly
      higher prevalence of obesity (p less than 0.05) than those in public schools. For
      primary and permanent teeth combined, children with higher BMI and WC had a lower
      prevalence of caries (p less than 0.05). Conclusion: The prevalence of obesity
      was high among male and female elementary school children. Overall caries
      activity was inversely proportional to BMI and WC.

PMID- 27874158
TI  - Urogenital myiasis caused by Psychoda albipennis.
AB  - Myiasis is a parasitic infestation of vertebrate animals caused by the eggs and
      larvae of flies within the Diptera species. Psychoda albipennis is a rare cause
      of urogenital myiasis in humans. We present the case of a 42-year-old male
      diagnosed with urogenital myiasis caused by Psychoda albipennis.

PMID- 27874160
TI  - Microvascular and macrovascular complications of type 2 diabetic mellitus in
      Central, Kingdom of Saudi Arabia.
AB  - OBJECTIVES: To determine the prevalence of macrovascular and microvascular
      complications of type 2 diabetes mellitus and its associated determinants. 
      Methods: We evaluated the online medical records of patients with type 2 diabetes
      mellitus who have been seen in chronic disease unit between April and June 2014.
      Seven hundred and forty-eight participants satisfied the inclusion criteria. Of
      these, 317 (42.4%) were males with a mean age of 57.9 years, 681 (64.3%) were
      obese with body mass index (BMI) of greater than 30, while only 9.6% had normal
      BMI (less than 25).  Results: Only 158 (21.1%) had controlled hemoglobin A1c
      level. Retinopathy prevalence was 14.8% and neuropathy was 5.6%. Macrovascular
      complications accounted for 12.1%. Patients' age and duration of diabetes were
      main predictors of developing complications. Patients with more than 20 years 
      history of diabetes have 30% more odds of developing the complications when
      compared to patients with less than 10 years of diabetes history. Each increment
      in age by one year increases the odds of developing microvascular complications
      by 4% and macro vascular complication by 2%.  Conclusion: Our results showed
      diabetic patients with poor glycemic control, and longer duration of diabetic
      history had higher prevalence of both macrovascular and microvascular.

PMID- 27874159
TI  - Evaluation of GeneXpert MTB/RIF for detection of Mycobacterium tuberculosis
      complex and rpo B gene in respiratory and non-respiratory clinical specimens at a
      tertiary care teaching hospital in Saudi Arabia.
AB  - OBJECTIVES: To assess the performance of Xpert MTB/RIF, an automated molecular
      test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF),
      against smear microscopy and culture method for diagnosis of MTB infection.
      Methods: This is a retrospective analysis of 103 respiratory and 137 non
      respiratory patient specimens suspected of tuberculosis at King Khalid University
      Hospital, Riyadh, Kingdom of Saudi Arabia performed between April 2014 and March
      2015. Each sample underwent smear microscopy, mycobacterial culture, and
      GeneXpert MTB/RIF test. Results: Fifteen out of 103 respiratory samples were
      smear and culture positive, whereas 9 out of 137 non-respiratory samples were
      smear positive. Out of 9 smear positive specimens, 8 were also culture positive.
      All 15 culture positive respiratory samples were detected by Xpert MTB/RIF
      (sensitivity  and positive predictive value [PPV]=100%). Similarly, all 8 culture
      positive non-respiratory specimens were identified by Xpert MTB/RIF (sensitivity
      100%; PPV 88.8%). The Xpert MTB/RIF detected only one false positive result in 88
      smear negative respiratory specimens (specificity 98.9%; negative predictive
      value [NPV]= 100%). All 125 smear negative non-respiratory specimens tested
      negative by culture and Xpert MTB/RIF (sensitivity, specificity, PPV, NPV= 100%).
      Conclusion: The performance of Xpert MTB/RIF was comparable to the gold standard
      culture method for identification of MTB in both respiratory and non-respiratory
      clinical specimens.

PMID- 27874161
TI  - Diffusion weighted magnetic resonance imaging in the diagnosis of parotid masses.
      Preliminary results.
AB  - OBJECTIVE: To demonstrate the diagnostic potentials of MRI, diffusion weighted
      imaging (DWI), and apparent diffusion coefficient (ADC) mapping in the detection
      of parotid masses correlated to the histopathological results. Methods: Study
      design was retrospective. Fifteen patients with parotid gland masses were
      included as the study group and contralateral normal parotis glands of same
      patients were taken as the control group. Patients with bilateral parotid gland
      tumors were excluded, 7 right-sided and 8 left-sided parotid masses were included
      in the research. The study took place at the Department of Radiology, Ankara,
      Turkey, between May 2012 and September 2014. Results: Apparent diffusion
      coefficient measurements of 15 parotis tumors in 1000 and 750 sec/mm2 b-values
      with comparison to the contralateral normal gland  parenchyma were demonstrated.
      Neurofibromas was predicted as the highest, and lipomas as the lowest ADC values.
      Pleomorphic adenomas, Warthin's tumor, and normal parotid parenchyma indicate
      significant statistical differences from each other on the basis of mean ADC
      values (p less than 0.05). Conclusion: The DWI and ADC mapping of parotis gland
      could aid in the differential diagnosis  of benign and malignant masses.

PMID- 27874162
TI  - Emerging Zika virus.
AB  - [No Abstract Available].

PMID- 27874163
TI  - Family profile of victims of child abuse and neglect in the Kingdom of Saudi
      Arabia.
AB  - [No Abstract Available].

PMID- 27874164
TI  - 'REM-related OSA': a forgotten diagnostic? Possible path to under-diagnosing
      sleep apnea.
AB  - INTRODUCTION: Restrictive criteria are proposed to define the disorder 'REM
      related OSA' disorder, and questions remain about its nosological transcendence
      and clinical management. AIM: To evaluate the criteria proposed to define 'REM
      related OSA', its relationship with cardio-metabolic comorbidity, and aspects
      related to it diagnostic. PATIENTS AND METHODS: Retrospective observational study
      of clinical and polysomnographic data from outpatients. 525 patients over 18
      years old who had an Apnea Hypopnea Index (AHI) = 5 (total, or partial, in REM
      and/or NREM) were included. RESULTS: 'Phase-dependent' subgroups were formed
      using a criterion based on the 'ratio = 2' and another 'strict' criterion based
      on a partial AHI = 5 compared to another partial AHI <5 (in REM or in NREM). In
      the 'strict REM-related OSA' subgroup, half of the patients showed an overall AHI
      < 5, with less severity in the respiratory parameters, but with lower comorbidity
      percentages. With the current diagnostic criteria, these patients would be
      excluded from the sleep apnea diagnosis. CONCLUSIONS: The application of the
      strict criterion to detect 'REM-related OSA' makes it possible to filter milder
      forms of sleep apnea associated with percentages of cardiovascular and/or
      metabolic comorbidity that are not significantly different from other more severe
      forms of sleep apnea. To avoid under-diagnosis, it would be advisable to review
      the sleep apnea diagnostic criteria and the indications of the reduced sleep
      apnea diagnostic techniques.

PMID- 27874166
TI  - [Massive cerebral air embolism following endoscopic retrograde
      cholangiopancreatography. A case report and review of the literature].
AB  - INTRODUCTION: Cerebral air embolism following endoscopic processes is an
      infrequent complication, but can have catastrophic consequences. CASE REPORT: An
      85-year-old male diagnosed with distal cholangiocarcinoma with criteria for
      unresectability who was submitted to placement of a biliary drainage prosthesis.
      Endoscopic retrograde cholangiopancreatography was performed to change the
      prosthesis. After the procedure, the patient's vital signs and level of
      consciousness underwent a decline, and orotracheal intubation was required. A
      computerised axial tomography scan of the head showed evidence of a massive air
      embolism with focal points of hyperacute ischaemia in both hemispheres. The
      patient later died. CONCLUSIONS: Cerebral air embolism following endoscopic
      retrograde cholangiopancreatography is infrequent, but potentially lethal.
      Manipulation of the bilio-intestinal wall in endoscopic examinations could give
      rise to communications between the lumen and the venous system. This, together
      with the high insufflation pressure used to conduct this test, would condition
      the passage of air to the portal venous system, and from there to the circulatory
      system. In the central nervous system, air bubbles would lead to a vascular
      obstruction, with the subsequent ischaemia and necrosis of tissues. An early
      diagnosis and life support therapy are essential. Its timely management can
      contribute to a better prognosis which, at least initially, is gloomy.

PMID- 27874165
TI  - [Montreal Cognitive Assessment Test: normalization and standardization for
      Spanish population].
AB  - INTRODUCTION: The Montreal Cognitive Assessment (MoCA) is a brief screening test
      that assesses the general cognitive state. It has become very popular and useful
      as an alternative resource for the traditional Mini-Mental State Examination.
      AIM: To normalize and to standardize the MoCA taking into account the
      sociodemographic characteristics of the Spanish population (INE data, 2012).
      SUBJECTS AND METHODS: The present study is part of the Normacog Project. Seven
      hundred participants were recruited (older than 18 years old). The effect of age,
      level of education and sex was analyzed on the performance of MoCA and
      percentiles and scalar score for nine ranges of age and scalar score adjusted by
      the level of education. RESULTS: Results showed a significant effect of age,
      level of education and sex on the cognitive performance of MoCA. However, sex was
      only significant in two domains (attention and delayed recall). Age, education
      and sex explained from 1.0% to 32.3% of the variance of the performance. The
      older participants with lower level of formal education obtained the worse
      performance shown in MoCA. Percentiles and scalar score for each range of age,
      and scalar score adjusted by the level of education were obtained. CONCLUSION:
      The normative data of the MoCA is provided taking into account the Spanish
      sociodemographic characteristics for adults in Spain and the cut-off to
      distinguish between normal cognitive performance and mild cognitive impairment
      according to different range of ages have been proposed.

PMID- 27874168
TI  - [53.a Reunion de la Sociedad Espanola de Neurofisiologia Clinica (I).
      Communications].

PMID- 27874169
TI  - [Is it really necessary to perform a lumbar puncture in all cases in the
      diagnosis of idiopathic intracranial hypertension?]

PMID- 27874167
TI  - [Antibiotics and gait disorders].
AB  - The neurological toxicity of many antibiotics has been reported in a number of
      articles and clinical notes. In this review antibiotics are classified according
      to the physiopathogenic mechanism that can give rise to a gait disorder, taking
      both clinical and experimental data into account. An exhaustive search was
      conducted in Google Scholar and PubMed with the aim of finding reviews, articles
      and clinical cases dealing with gait disorders secondary to different
      antibiotics. The different antibiotics were separated according to the
      physiopathogenic mechanism that could cause them to trigger a gait disorder. They
      were classified into antibiotics capable of producing cerebellar ataxia,
      vestibular ataxia, sensitive ataxia or an extrapyramidal gait disorder. The main
      aim was to group all the drugs that can give rise to a gait disorder, in order to
      facilitate the clinical suspicion and, consequently, the management of patients.

PMID- 27874170
TI  - [Neurocultural mosaic. Neuroscience in daily life and the news].

PMID- 27874171
TI  - Anthropologists' views on race, ancestry, and genetics.
AB  - : Controversies over race conceptualizations have been ongoing for centuries and
      have been shaped, in part, by anthropologists. OBJECTIVE: To assess
      anthropologists' views on race, genetics, and ancestry. METHODS: In 2012 a broad
      national survey of anthropologists examined prevailing views on race, ancestry,
      and genetics. RESULTS: Results demonstrate consensus that there are no human
      biological races and recognition that race exists as lived social experiences
      that can have important effects on health. DISCUSSION: Racial privilege affects
      anthropologists' views on race, underscoring the importance that anthropologists
      be vigilant of biases in the profession and practice. Anthropologists must
      mitigate racial biases in society wherever they might be lurking and quash any
      sociopolitical attempts to normalize or promote racist rhetoric, sentiment, and
      behavior.

PMID- 27874172
TI  - Development of crizotinib, a rationally designed tyrosine kinase inhibitor for
      non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the number one cause of global mortality.
      Despite aggressive treatment, the prognosis is dismal. Patients with advanced
      NSCLC have a median survival of 4 months from the time of diagnosis. Fortunately,
      molecularly based approaches to drug discovery have yielded a tyrosine kinase
      inhibitor, crizotinib, which significantly prolongs median progression-free
      survival in a subset of patients. Although initial clinical trial results
      demonstrate crizotinib has a promising role to play in NSCLC treatment,
      development of resistance leaves much to be elucidated about how to effectively
      combat this deadly disease. In this review, we follow the discovery and
      development of crizotinib from bench to bedside and provide an example of
      successful bottom-up drug design. Then, we explore the clinical trial results
      that fast-tracked its eventual use as a frontline therapy for sensitive NSCLC
      patients and the development of resistance. Lastly, we discuss the potential for
      future uses of crizotinib both within and beyond NSCLC.

PMID- 27874175
TI  - Predictors of Engagement in Family Mediation and Outcomes for Families that Fail
      to Engage.
AB  - An important limitation to the effectiveness of family mediation in assisting
      separated parents is parents failing to engage in the mediation process. In 524
      parents who presented to a telephone-based mediation service, 113 (22%)
      initiating parents withdrew from mediation before the other parent was invited to
      participate, 241 (46%) initiating parents had respondent parents who declined to
      participate in mediation, and 170 cases (33%) completed mediation. We tested
      whether socio-demographic variables, psychological distress, coparental acrimony,
      parenting problems, or children's behavioral difficulties predicted mediation
      engagement. High interparental acrimony predicted failure to engage in mediation,
      but none of the other variables predicted mediation engagement. We followed a
      sample of 131 families that did not mediate and found they showed elevated
      psychological distress, acrimony, parenting problems and child adjustment
      difficulties, which remained unchanged 6 months later. Further research is needed
      to explore strategies to enhance respondent parent engagement with mediation, and
      to address the negative outcomes for those separated families not proceeding with
      mediation.

PMID- 27874174
TI  - Compound heterozygous mutations in the IFT140 gene cause Opitz trigonocephaly C
      syndrome in a patient with typical features of a ciliopathy.
AB  - < We report on an infant with Opitz trigonocephaly C syndrome (OTCS), who also
      had manifestations of ciliopathy, including short ribs (non-asphyxiating),
      trident acetabular roofs, postaxial polydactyly cone-shaped epiphyses, and
      dysplasia of the renal, hepatic and pancreatic tissues. To investigate the
      molecular cause, we used an exome sequencing strategy followed by Sanger
      sequencing. Two rare variants, both predicted to result in loss of functional
      protein, were identified in the IFT140 gene; a substitution at the splice donor
      site of exon 24 (c.723 + 1 G > T) and a 17 bp deletion, impacting the first
      coding exon (c.-11_6del). The variants were confirmed as being biallelic using
      Sanger sequencing, showing that the splice variant was inherited from the
      propositus mother and the deletion from the father. To date, Mainzer-Saldino
      syndrome, Jeune syndrome, and a form of nonsyndromic retinal dystrophy, have been
      identified as ciliopathies caused by IFT140 mutations. We provide the first
      description of an OTCS phenotype that appears to result from IFT140 mutations.
      The presentation of this patient is consistent with previous reports showing that
      OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy.

PMID- 27874173
TI  - Identification and validation of an eight-gene expression signature for
      predicting high Fuhrman grade renal cell carcinoma.
AB  - Clear cell renal cell carcinoma (ccRCC) is a malignancy with heterogeneous
      outcomes. Currently, renal mass biopsies are commonly employed to extract disease
      characteristics and aid prognosis. Although the pathological diagnosis of
      malignant disease is accurate in contemporary reports, the classification of
      Fuhrman grade using biopsy specimens remains far from promising. To generate a
      gene signature to distinguish high-grade ccRCC, we used the cancer genome atlas
      (TCGA) database to develop a gene expression signature for distinguishing high
      grade (G3/4) from low-grade (G1/2) disease. The expression profile was further
      validated for performance and clinical use in 283 frozen renal cancer samples and
      127 ex vivo renal mass biopsy samples, respectively. The area under curve (AUC)
      was used to quantify discriminative ability and was compared using the De-long
      test. Using the discovery dataset, we identified a 24-gene signature for high
      grade disease with an AUC of 0.884. After applied to the development dataset, an
      eight-gene profile was defined and achieved an AUC of 0.823. Accuracy of eight
      gene panel was maintained in the renal mass biopsies (RMB) samples (AUC = 0.821).
      In summary, using three-stage design, we validated an eight-gene expression
      signature for predicting high Fuhrman grade of ccRCC. This tool may help to
      reveal the characteristics of ccRCC biopsy specimens.

PMID- 27874176
TI  - Effects of Tai Chi on Cognition and Fall Risk in Older Adults with Mild Cognitive
      Impairment: A Randomized Controlled Trial.
AB  - OBJECTIVES: To examine whether combined center- and home-based Tai Chi training
      can improve cognitive ability and reduce physiological fall risk in older adults
      with amnestic mild cognitive impairment (a-MCI). DESIGN: Randomized controlled
      trial. SETTING: Chiang Mai, Thailand. PARTICIPANTS: Adults aged 60 and older who
      met Petersen's criteria for multiple-domain a-MCI (N = 66). INTERVENTION: Three
      weeks center-based and 12 weeks home-based Tai Chi (50 minutes per session, 3
      times per week). MEASUREMENTS: Cognitive tests, including Logical Memory (LM)
      delayed recall, Block Design, Digit Span forward and backward, and Trail-Making
      Test Part B-A (TMT B-A), and fall risk index using the Physiological Profile
      Assessment (PPA). RESULTS: At the end of the trial, performance on LM, Block
      Design, and TMT B-A were significantly better for the Tai Chi group than the
      control group after adjusting for baseline test performance. The Tai Chi group
      also had significantly better composite PPA score and PPA parameter scores: knee
      extension strength, reaction time, postural sway, and lower limb proprioception.
      CONCLUSION: Combined center- and home-based Tai Chi training three times per week
      for 15 weeks significantly improved cognitive function and moderately reduced
      physiological fall risk in older adults with multiple-domain a-MCI. Tai Chi may
      be particularly beneficial to older adults with this condition.

PMID- 27874177
TI  - The Differentiation of Menstrual from Venous Blood and Other Body Fluids on
      Various Substrates Using ATR FT-IR Spectroscopy.
AB  - Crime scene investigators and laboratory analysts use chemical tests to detect
      and differentiate body fluids. Testing often requires a sample of the stain, and
      the chemicals may cause degradation of the fluid or interfere with subsequent
      tests. Colorimetric chemical tests do not differentiate between different types
      of the same fluid, such as venous and menstrual blood, and there is no
      presumptive test available to simultaneously differentiate several body fluids.
      In this study, we recorded ATR FT-IR spectra of venous and menstrual blood,
      semen, saliva, and breastmilk. Neat and simulated casework body fluid samples
      were analyzed on cotton, nylon, wood, paper, and glass substrates. Differences in
      fluid composition, including proteins and small molecules, resulted in spectral
      differences. Venous and menstrual blood is differentiated by the peak at 1039 cm
      1 attributed to phosphoric acid found in menstrual blood. Peak intensity is
      influenced by the porosity and weave of the substrate fabric.

PMID- 27874178
TI  - Targeted Exercise Training to Optimize Leg Power, Leg Speed, and Mobility in
      Older Adults.

PMID- 27874179
TI  - Association Between Chewing Difficulty and Symptoms of Depression in Adults:
      Results from the Korea National Health and Nutrition Examination Survey.
AB  - OBJECTIVES: To assess the association between chewing difficulty and symptoms of
      depression in a representative sample of the Korean population. DESIGN: Cross
      sectional. SETTING: Korea National Health and Nutrition Examination Survey
      (KNHANES). PARTICIPANTS: KNHANES participants (N = 5,158). MEASUREMENTS: Chewing
      difficulty was assessed according to the self-reported presence of chewing
      problems using a structured questionnaire. Symptoms of depression were defined as
      having feelings of sadness or depression consecutively over 2 weeks during the
      last 12 months. Multivariable logistic regression analysis was used to determine
      the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) of the
      associations between chewing difficulty and symptoms of depression, adjusted for
      age; sex; monthly household income; education; number of teeth; number of
      decayed, missing, or filled permanent teeth; periodontitis; state of dentition;
      tooth brushing frequency; regular dental visits; smoking status; alcohol
      consumption; hypertension; diabetes mellitus; and obesity. The interaction
      effects between chewing difficulty and confounders were evaluated, and age- and
      sex-stratified analyses were performed. RESULTS: There was a significant positive
      association between chewing difficulty and symptoms of depression in the fully
      adjusted model (AOR = 1.86, 95% CI = 1.48-2.33). The strength of the association
      was highest in men aged 60 and older (AOR = 3.28, 95% CI = 1.54-7.00).
      CONCLUSION: Chewing difficulty was independently associated with symptoms of
      depression in a representative sample of Korean adults.

PMID- 27874181
TI  - AGS Position Statement: Making Medical Treatment Decisions for Unbefriended Older
      Adults.
AB  - In this position statement, we define unbefriended older adults as patients who:
      (1) lack decisional capacity to provide informed consent to the medical treatment
      at hand; (2) have not executed an advance directive that addresses the medical
      treatment at hand and lack capacity to do so; and (3) lack family, friends or a
      legally authorized surrogate to assist in the medical decision-making process.
      Given the vulnerable nature of this population, clinicians, health care teams,
      ethics committees and other stakeholders working with unbefriended older adults
      must be diligent when formulating treatment decisions on their behalf. The
      process of arriving at a treatment decision for an unbefriended older adult
      should be conducted according to standards of procedural fairness and include
      capacity assessment, a search for potentially unidentified surrogate decision
      makers (including non-traditional surrogates) and a team-based effort to
      ascertain the unbefriended older adult's preferences by synthesizing all
      available evidence. A concerted national effort is needed to help reduce the
      significant state-to-state variability in legal approaches to unbefriended
      patients. Proactive efforts are also needed to identify older adults, including
      "adult orphans," at risk for becoming unbefriended and to develop alternative
      approaches to medical decision making for unbefriended older adults. This
      document updates the 1996 AGS position statement on unbefriended older adults.

PMID- 27874180
TI  - Passive Drip Stain Formation Dynamics of Blood onto Hard Surfaces and Comparison
      with Simple Fluids for Blood Substitute Development and Assessment<sup/>.
AB  - The spreading dynamics of blood dripping onto hard surfaces is compared to two
      spreading models. Samples of human blood, porcine blood, and Millipore(r) water
      were dripped onto cardboard, foamcore, and glass surfaces in low velocity passive
      drip simulations. Final stain diameter, the total number of spines and scallops,
      and angle of impact were measured and analyzed. Spreading is best predicted by
      applying the concept of effective viscosity to the Scheller and Bousfield (R2  =
      0.91) and Roisman (R2  = 0.89) spreading models. In the tested conditions, blood
      spreads with Newtonian tendencies; however, has quantifiable differences in stain
      appearance to Newtonian fluids like water. This is encouraging for the
      development of water-based fluids as synthetic blood substitutes (SBSs). The work
      presents an assessment platform to quantify and score the performance of simple
      water-based fluids using final stain diameter (6 points) and number of spines and
      scallops (6 points) at six dripping heights between 20 and 120 cm. The angle of
      impact of a stain alone is not a sensitive measure of SBS performance, but stain
      formation scores the SBS's performance with another 1 point. Together these
      features generate a quantitative relative ranking system, of a maximum possible
      13 points, that can be used to support the use of a particular fluid for the
      creation of a drip stain. The performance of twenty simple fluids in the
      simulated dripping assessment test is described.

PMID- 27874182
TI  - Synthesis and Analysis of Glucuronic Acid-Conjugated Metabolites of 4-Bromo-2,5
      Dimethoxyphenethylamine.
AB  - In the study reported here, two glucuronic acid-conjugated metabolites of 4-bromo
      2,5-dimethoxyphenethylamine (2C-B)-a ring-substituted psychoactive phenethylamine
      were chemically synthesized for the first time and a method for analyzing them in
      urine was developed. beta-D-Glucuronide of 4-bromo-2,5
      dimethoxyphenylethylalcohol was successfully synthesized using methyl 2,3,4-tri
      Omicron-acetyl-1-O-(trichloroacetimidoyl)-alpha-D-glucuronate as a glucuronyl
      donor and boron trifluoride diethylether complex as a Lewis acid catalyst. beta-D
      Glucuronide of 4-bromo-2,5-dimethoxyphenylacetic acid was synthesized by
      condensing 4-bromo-2,5-dimethoxyphenylacetic acid and benzyl D-glucuronate
      followed by benzyl group deprotection based on catalytic hydrogenation. Two
      glucuronic acid-conjugated metabolites of 2C-B in urine were qualitatively and
      semiquantitatively evaluated via direct liquid chromatography/mass spectrometry
      (LC/MS) analysis of a diluted urine sample. The simple method proposed is
      expected to be useful for studying the metabolic fate of 2C-B.

PMID- 27874183
TI  - Under Our Nose: The Use of GIS Technology and Case Notes to Focus Search Efforts.
AB  - Missing person searches can entail much time, effort, and resources. With
      scientific data and techniques increasingly available to law enforcement and
      investigations units, can these tools be used to predict likely areas where
      persons or remains may be discovered, especially in cases where little to no
      information about the disappearance is available? A retrospective study of
      seventy-three (73) cases was conducted in Onondaga County, New York, U.S.A., in
      order to explore this question. Quantitative (geospatial) and qualitative
      (investigator notes) data were utilized to determine whether patterns exist that
      may assist in investigations of recent and "cold" missing person cases. Results
      showed a majority of cases with relative proximity (<5 miles) between victim last
      seen (VLS) and body recovered (BR) locations. Furthermore, investigators' notes
      demonstrated repeated descriptors reflecting natural or cultural features
      associated with hidden, clandestine provenance (e.g., near bodies of water,
      wooded areas). With future external validation of this study, consistent priority
      areas may be identified as foci of searches; these priority areas ideally should
      be thoroughly checked/cleared before the search zone is expanded.

PMID- 27874184
TI  - Antenatal ultrasound features in fetuses with gastroschisis and its prediction in
      neonatal outcome.
AB  - BACKGROUND: Gastroschisis is the most common major congenital anomaly managed by
      paediatric surgeons. The significance of certain associated antenatal ultrasound
      features in determining fetal outcome is under discussion. AIM: The study aims to
      define if associated antenatal ultrasound features of gastroschisis are useful
      prognostic markers for fetal outcome. By establishing the significance of
      features, including extra- and intra-abdominal bowel dilatation, stomach
      herniation, stomach dilatation, bowel matting, growth restriction, abnormal
      umbilical artery (UA) Doppler ultrasounds, and abnormal amniotic fluid volume, it
      is hoped clinicians will have enhanced ability to counsel parents about the
      likely outcomes for their infant. MATERIALS AND METHODS: Retrospective analysis
      of ultrasound images, reports and medical records of 101 pregnancies affected by
      fetal gastroschisis managed by the Royal Brisbane and Women's Hospital Maternal
      and Fetal Medicine Department over a 13 and a half year period was performed. The
      presence of ultrasound features during antenatal surveillance corresponded to
      fetal outcome measures, including the diagnosis of postnatal complex
      gastroschisis, the number of operations required, length of parenteral feeding
      and length of stay in neonatal intensive care. RESULTS: The only statistically
      significant predictor of complex cases of gastroschisis was extra-abdominal bowel
      dilatation. Although a statistically significant feature, approximately three
      quarters (44/59) of all infants with gastroschisis with associated extra
      abdominal bowel dilatation had simple gastroschisis. CONCLUSIONS: Extra-abdominal
      bowel dilatation is a statistically significant marker of complex gastroschisis
      and associated morbidity. Its presence in infants who had uncomplicated outcomes,
      suggests that clinically, its usefulness in antenatal counselling is still
      debatable.

PMID- 27874185
TI  - Translating Delirium Prevention Strategies for Elderly Adults with Hip Fracture
      into Routine Clinical Care: A Pragmatic Clinical Trial.
AB  - OBJECTIVES: To compare the feasibility (adherence) and effectiveness (prevalence
      of delirium, length of stay, mortality, discharge site) of delirium-friendly
      preprinted postoperative orders (PPOs) for individuals with hip fracture,
      administered by regular orthopedic nurses, with routine postoperative orders.
      DESIGN: Pragmatic clinical trial to evaluate a quality improvement intervention.
      SETTING: Tertiary care hospital. PARTICIPANTS: Individuals aged 65 and older
      admitted for hip fracture repair (N = 283). INTERVENTION: PPOs with delirium
      friendly options and doses for nighttime sedation, analgesia, and nausea and
      attention to catheter removal and bowel movements. MEASUREMENTS: Adherence to PPO
      was compared with adherence to routine orders. Drug doses were recorded. Presence
      of delirium was documented using the Confusion Assessment Method and the Mini
      Mental State Examination on postoperative Days 1, 3, and 5. Length of stay,
      discharge site, and in-hospital mortality were recorded. RESULTS: Orthopedic
      nurses adhered reasonably well with delirium-friendly PPOs. Of 283 participants,
      42% developed postoperative delirium, with significantly less delirium in the
      intervention group (intervention 33%, control 51%, P = .001). The effect of the
      intervention was stronger in individuals with preexisting dementia (intervention
      60%, control 97%, P < .001). Participants with postoperative delirium had longer
      hospital stays and were more likely to die or be discharged to a nursing home,
      but there was no significant between-group difference in these outcomes.
      CONCLUSION: It is possible to introduce delirium-friendly PPOs into routine post
      hip fracture care in a representative elderly population including individuals
      with dementia. Delirium-friendly PPOs executed by regular nursing staff resulted
      in a significant reduction in postoperative delirium but no difference in other
      outcomes.

PMID- 27874186
TI  - Lessons Learned from Autopsying an Unidentified Body with Iodine-125 Seeds
      Implanted for Prostate Brachytherapy.
AB  - We report here lessons learned from an autopsy case involving radioactive
      materials. We performed an autopsy of an unidentified mummified man with no
      available medical history whom from imaging findings we suspected had received
      radioactive seed implants for prostate brachytherapy. We returned the excised
      prostate and seeds to the body. A few days later, the body was identified by DNA
      matching and cremated. According to the man's medical record, he had undergone
      iodine-125 seeds implantation for prostate cancer 11 months earlier. We should
      have removed the radioactive seeds from the body to prevent radiation exposure to
      the bereaved family and/or environmental pollution due to cremation.
      Surprisingly, one seed was found in the stored prostate specimen. Forensic
      experts should be cognizant of the risk of both radiation exposure in the autopsy
      room and environmental pollution. We must remain abreast of the latest advances
      in medicine.

PMID- 27874187
TI  - Performance of a new HPV and biomarker assay in the management of hrHPV positive
      women: Subanalysis of the ongoing multicenter TRACE clinical trial (n > 6,000) to
      evaluate POU4F3 methylation as a potential biomarker of cervical precancer and
      cancer.
AB  - The ongoing Triage and Risk Assessment of Cervical Precancer by Epigenetic
      Biomarker (TRACE) prospective, multicenter study aimed to provide a clinical
      evaluation of the CONFIDENCETM assay, which comprises a human papillomavirus
      (HPV) DNA and a human epigenetic biomarker test. Between 2013 and 2015 over 6,000
      women aged 18 or older were recruited in Hungary. Liquid-based cytology (LBC),
      high-risk HPV (hrHPV) DNA detection and single target host gene methylation test
      of the promoter sequence of the POU4F3 gene by quantitative methylation-specific
      polymerase chain reaction (PCR) were performed from the same liquid-based
      cytology sample. The current analysis is focused on the baseline cross-sectional
      clinical results of 5,384 LBC samples collected from subjects aged 25 years or
      older. The performance of the CONFIDENCE HPVTM test was found to be comparable to
      the cobas(r) HPV test with good agreement. When applying the CONFIDENCE MarkerTM
      test alone in hrHPV positives, it showed significantly higher sensitivity with
      matching specificity compared to LBC-based triage. For CIN3+ histological
      endpoint in the age group of 25-65 and 30-65, the methylation test of POU4F3
      achieved relative sensitivities of 1.74 (95% CI: 1.25-2.33) and 1.64 (95% CI:
      1.08-2.27), respectively, after verification bias adjustment. On the basis of our
      findings, POU4F3 methylation as a triage test of hrHPV positives appears to be a
      noteworthy method. We can reasonably assume that its quantitative nature offers
      the potential for a more objective and discriminative risk assessment tool in the
      prevention and diagnostics of high-grade cervical intraepithelial neoplasia (CIN)
      lesions and cervical cancer.

PMID- 27874188
TI  - Clinically Detectable Dental Identifiers Observed in Intra-oral Photographs and
      Extra-oral Radiographs, Validated for Human Identification Purposes.
AB  - Screening the prevalence and pattern of dental identifiers contributes toward the
      process of human identification. This research investigated the uniqueness of
      clinical dental identifiers in photographs and radiographs. Panoramic and lateral
      cephalometric radiographs and five intra-oral photographs of 1727 subjects were
      used. In a target set, two observers examined different subjects. In a subset,
      both observers examined the same subjects (source set). The distance between
      source and target subjects was quantified for each identifier. The percentage of
      subjects in the target set being at least as close as the correct subject was
      assessed. The number of molars (34.6%), missing teeth (42%), and displaced teeth
      (59.9%) were the most unique identifiers in photographs and panoramic and lateral
      cephalometric radiographs, respectively. The pattern of rotated teeth (14.9%) was
      the most unique in photographs, while displaced teeth was in panoramic (37.6%)
      and lateral cephalometric (54.8%) radiographs. Morphological identifiers were the
      most unique, highlighting their importance for human identifications.

PMID- 27874189
TI  - Incapacity of the Mind Secondary to Medication Misuse as a Not Criminally
      Responsible Defense.
AB  - The manifestations of disorders of the mind may play a role in the occurrence of
      criminal behavior. In the majority of the cases, the presence of a psychiatric
      disorder is cited as the reason that an individual was not fully aware of his
      behavior. However, other conditions, such as seizure disorders or hypoglycemia,
      have also been linked to an inability to understand the nature and consequences
      of one's actions. On occasion, these situations can be explained by a state of
      automatism that may be described as insane or noninsane. In this article, we
      describe the case of a 77-year-old man, suffering from Parkinson's disease, where
      the issue of criminal responsibility associated with incapacity of the mind
      secondary to medication misuse was raised. We elaborate on the thinking behind
      this opinion and the implications according to Canadian law. Although the legal
      outcome of this case is specific to our jurisdiction, the clinical implication
      may be common to any patient suffering from a similar condition and may inform
      physicians, families, and lawyers.

PMID- 27874190
TI  - The Value of Outsourcing Selected Cases in a Medical Examiner Population: A 10
      Year Experience.
AB  - Due to increasing caseloads and inadequate staffing, the burden on
      Coroner/Medical Examiner Offices to comply with recommended autopsy limits for
      forensic pathologists (FPs) has been difficult. Since 2006, pathologists at the
      University of Alabama at Birmingham have performed select autopsies for the
      Alabama Department of Forensic Sciences. Each case was reviewed by a state FP and
      scene investigator to determine appropriateness for referral. All referred cases
      received full postmortem examination including microscopic examination and
      collection of toxicological samples, and toxicology was ordered by the referring
      FP as appropriate. The final cause and manner of death were determined by the
      referring state FP after review of all findings. A majority of the 421 cases were
      ruled accidental deaths (233), most due to drug toxicity. Of the 178 natural
      deaths, 118 were attributed to cardiovascular disease. Outsourcing select
      forensic cases can be educational and an effective tool to manage workflow
      without compromising quality.

PMID- 27874191
TI  - Nitrate and Nitrite Determination in Gunshot Residue Samples by Capillary
      Electrophoresis in Acidic Run Buffer.
AB  - Simultaneous determination of nitrate and nitrite in gunshot residue has been
      conducted by capillary electrophoresis using an acidic run buffer (pH 3.5). In
      previously developed capillary electrophoretic methods, alkaline pH separation
      buffers were used where nitrite and nitrate possess similar electrophoretic
      mobility. In this study, the electroosmotic flow has been reversed by using low
      pH running buffer without any additives. As a result of reversing the
      electroosmotic flow, very fast analysis has been actualized, well-defined and
      separated ion peaks emerge in less than 4 min. Besides, the limit of detection
      was improved by employing large volume sample stacking. Limit of detection values
      were 6.7 and 4.3 MUM for nitrate and nitrite, respectively. In traditional
      procedure, mechanical agitation is employed for extraction, while in this work
      the extraction efficiency of ultrasound mixing for 30 min was found sufficient.
      The proposed method was successfully applied to authentic gunshot residue
      samples.

PMID- 27874192
TI  - Comparing Methods to Assess Intraobserver Measurement Error of 3D Craniofacial
      Landmarks Using Geometric Morphometrics Through a Digitizer Arm.
AB  - Intraobserver error (INTRA-OE) is the difference between repeated measurements of
      the same variable made by the same observer. The objective of this work was to
      evaluate INTRA-OE from 3D landmarks registered with a Microscribe, in different
      datasets: (A) the 3D coordinates, (B) linear measurements calculated from A, and
      (C) the six-first principal component axes. INTRA-OE was analyzed by digitizing
      42 landmarks from 23 skulls in three events two weeks apart from each other.
      Systematic error was tested through repeated measures ANOVA (ANOVA-RM), while
      random error through intraclass correlation coefficient. Results showed that the
      largest differences between the three observations were found in the first
      dataset. Some anatomical points like nasion, ectoconchion, temporosphenoparietal,
      asterion, and temporomandibular presented the highest INTRA-OE. In the second
      dataset, local distances had higher INTRA-OE than global distances while the
      third dataset showed the lowest INTRA-OE.

PMID- 27874193
TI  - ALK oncoproteins in atypical inflammatory myofibroblastic tumours: novel RRBP1
      ALK fusions in epithelioid inflammatory myofibroblastic sarcoma.
AB  - ALK oncogenic activation mechanisms were characterized in four conventional
      spindle-cell inflammatory myofibroblastic tumours (IMT) and five atypical IMT,
      each of which had ALK genomic perturbations. Constitutively activated ALK
      oncoproteins were purified by ALK immunoprecipitation and electrophoresis, and
      were characterized by mass spectrometry. The four conventional IMT had TPM3/4-ALK
      fusions (two cases) or DCTN1-ALK fusions (two cases), whereas two atypical
      spindle-cell IMT had TFG-ALK and TPM3-ALK fusion in one case each, and three
      epithelioid inflammatory myofibroblastic sarcomas had RANBP2-ALK fusions in two
      cases, and a novel RRBP1-ALK fusion in one case. The epithelioid inflammatory
      myofibroblastic sarcoma with RRBP1-ALK fusion had cytoplasmic ALK expression with
      perinuclear accentuation, different from the nuclear membranous ALK localization
      in epithelioid inflammatory myofibroblastic sarcomas with RANBP2-ALK fusions.
      Evaluation of three additional uncharacterized epithelioid inflammatory
      myofibroblastic sarcomas with ALK cytoplasmic/perinuclear- accentuation
      expression demonstrated RRBP1-ALK fusion in two cases. These studies show that
      atypical spindle-cell IMT can utilize the same ALK fusion mechanisms described
      previously in conventional IMT, whereas in clinically aggressive epithelioid
      inflammatory myofibroblastic sarcoma we identify a novel recurrent ALK oncogenic
      mechanism, resulting from fusion with the RRBP1 gene. Copyright (c) 2016
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 27874196
TI  - Prenatal diagnosis of upper extremity malformations with ultrasonography:
      Diagnostic features and perinatal outcome.
AB  - OBJECTIVE: The aim of this study was to assess the sonographic (US)
      characteristics, associated malformations, chromosomal status, and perinatal
      outcomes of fetuses with an upper extremity malformation (UEM) detected by US
      examination. METHODS: The data of all patients evaluated in the Department of
      Obstetrics and Gynecology, Prenatal Diagnosis Unit between 2010 and 2015 were
      searched for UEM. RESULTS: A total of 51 cases with UEM were detected. Eighteen
      cases (35.2%) had defects in the formation of body parts (absence of
      hand/forearm/digits); 25 cases (49%) had defects in differentiation
      (contractures, syndactyly), and 8 cases (15.6%) had duplication defects
      (polydactyly). The specificity of prenatal US for UEM was 96.2%. Ten cases
      (19.7%) had isolated UEM, and 41 cases (80.3%) had additional anomalies, most of
      which were cardiac, central nervous system, or facial malformations. Although
      chromosomal structure in isolated cases was normal in 9 of 10 cases (90%), 15 of
      41 cases (36.5%) with multiple defects showed abnormal karyotypes. The
      chromosomal constituents of nine cases (17.6%) were not available. Although the
      postnatal outcome of isolated cases was favorable except for the presence of
      orthopedic problems, complex UEMs with or without abnormal karyotypes were always
      lethal (97.5%). CONCLUSIONS: UEMs associated with other malformations are usually
      a sign of underlying severe chromosomal abnormalities, and the prognosis is poor.
      In contrast, chromosomal structure in isolated cases is normal, and the perinatal
      and postnatal outcomes are good. In general, US is an effective tool in
      differentiating fetuses with isolated UEM from those with UEM associated with
      additional malformations. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound
      45:267-276, 2017.

PMID- 27874195
TI  - Double peak sensory nerve action potentials to single stimuli in nerve conduction
      studies.
AB  - INTRODUCTION: In humans, sensory nerve action potentials (SNAPs) can show 2
      separate deflections, i.e., double peak potentials (DPp), which necessarily means
      that 1 peak is delayed with respect to the other. DPps may have various origins
      and be due to either physical or physiological properties. METHODS: We review the
      nature of commonly encountered DPps in clinical practice, provide the most likely
      interpretations for their physiological origin, and assess their reproducibility
      and clinical utility. RESULTS: We classified the DPps into 3 categories: (1)
      simultaneous anodal and cathodal stimulation. (2) simultaneous recording from 2
      different nerves at the same site, and (3) SNAP desynchronization. CONCLUSIONS:
      Although the recording of DPps is not a standardized neurophysiological method,
      their study brings interesting cues about the physiology of nerve stimulation and
      paves the way for clinical application of such an observation. Muscle Nerve 55:
      619-625, 2017.

PMID- 27874197
TI  - Regional Gradients in Institutional Cesarean Delivery Rates: Evidence from Five
      Countries in Asia.
AB  - BACKGROUND: Although the influence of the type of institutional setting on the
      risk of cesarean birth is well documented, less is known about the regional
      variations in institution-specific cesarean rates within countries. Our purpose
      was to examine regional variations in cesarean rates across public and private
      facilities in five Asian countries with a sizeable private sector: Bangladesh,
      India, Indonesia, Pakistan, and the Philippines. METHODS: Demographic Health
      Survey data and a hierarchical model were used to assess regional variations in
      the mode of delivery while controlling for a wide range of socioeconomic,
      demographic, and maternal risk factors. RESULTS: The risk of cesarean birth was
      greater in a private facility than in a government hospital by 36-48 percent in
      India and Indonesia and by 130 percent in Bangladesh. Regional gradients in
      cesarean birth were found to be steeper for deliveries in private facilities than
      in government hospitals in India, Indonesia, and the Philippines. The residents
      of India's high-use states were 55 percent more likely to undergo a cesarean
      delivery in a government hospital and 83 percent more likely in a private
      facility than their counterparts in the medium-use states. Similarly, compared to
      the residents of the Philippines's medium-use provinces, giving birth in a
      government facility increased the likelihood of a cesarean delivery by 84 percent
      and by 173 percent in a private facility. CONCLUSIONS: Large regional variations
      in cesarean rates suggest the need for more informed clinical decision making
      with respect to the selection of cases for cesarean delivery and the
      establishment of well-developed guidelines and standards at the provincial or
      state levels.

PMID- 27874194
TI  - Slow Gait Speed and Risk of Long-Term Nursing Home Residence in Older Women,
      Adjusting for Competing Risk of Mortality: Results from the Study of Osteoporotic
      Fractures.
AB  - OBJECTIVES: To determine whether slow gait speed increases the risk of costly
      long-term nursing home residence when accounting for death as a competing risk
      remains unknown. DESIGN: Longitudinal cohort study using proportional hazards
      models to predict long-term nursing home residence and subdistribution models
      with death as a competing risk. SETTING: Community-based prospective cohort
      study. PARTICIPANTS: Older women (mean age 76.3) participating in the Study of
      Osteoporotic Fractures who were also enrolled in Medicare fee-for-service plans
      (N = 3,755). MEASUREMENTS: Gait speed was measured on a straight 6-m course and
      averaged over two trials. Long-term nursing home residence was defined using a
      validated algorithm based on Medicare Part B claims for nursing home-related
      care. RESULTS: Participants were followed until long-term nursing home residence,
      disenrollment from Medicare plan, death, or December 31, 2010. Over the follow-up
      period (median 11 years), 881 participants (23%) experienced long-term nursing
      home residence, and 1,013 (27%) died before experiencing this outcome. Slow
      walkers (55% of participants with gait speed <1 m/s) were significantly more
      likely than fast walkers to reside in a nursing home long-term (adjusted hazards
      ratio (aHR) = 1.79, 95% confidence interval (CI) = 1.54-2.09). Associations were
      attenuated in subdistribution models (aHR = 1.52, 95% CI = 1.30-1.77) but
      remained statistically significant. CONCLUSION: Older community-dwelling women
      with slow gait speed are more likely to experience long-term nursing home
      residence, as well as mortality without long-term residence. Ignoring the
      competing mortality risk may overestimate long-term care needs and costs.

PMID- 27874198
TI  - Crataeva nurvala nanoparticles inhibit virulence factors and biofilm formation in
      clinical isolates of Pseudomonas aeruginosa.
AB  - Green synthesized nanoparticles have gained great attention due to their non
      toxic and non-hazardous nature. In the present study, bark extract of the
      medicinal plant in Ayurveda Crataeva nurvala (Buch-Ham) (CN) was chosen for the
      biosynthesis of silver nanoparticles (AgNPs). These NPs were characterized by
      Ultra violet visible spectroscopy, Fourier Transform Infra Red, Atomic Force
      Microscopy, and Transmission Electron Microscopy (TEM). The average particle size
      of green synthesized CN-AgNPs was 15.2 +/- 1.01 nm. Gas chromatography- mass
      spectrometry analysis of methanolic bark extract involved in the formation of CN
      AgNPs revealed lupeol as a major active component. In this study, CN-AgNPs (15
      MUg ml-1 ) efficiently suppressed the production of quorum sensing mediated
      virulence factors viz. pyocyanin, protease, hemolysin, and biofilm formation in
      Pseudomonas aeruginosa. The pyocyanin production was strongly inhibited (74.64%)
      followed by proteolysis (47.3%) and hemolysin production (47.7%). However, the
      biofilm forming ability was maximally reduced up to 79.70%. Moreover, the
      Confocal Laser Scanning Microscopic Analysis showed that CN-AgNPs inhibit
      colonization of P. aeruginosa on to the surface. Furthermore, TEM analysis
      revealed internalization of CN-AgNPs inside the bacterial cell. It is concluded
      that green synthesized AgNPs have great potential to inhibit virulence factors
      and biofilm forming ability of drug-resistant clinical isolates of P. aeruginosa.

PMID- 27874199
TI  - Glucose and lipid levels with lanreotide autogel 120 mg in treatment-naive
      patients with acromegaly: data from the PRIMARYS study.
AB  - OBJECTIVE: Impaired glycaemic control, characteristic of acromegaly, can be
      exacerbated by treatment with somatostatin analogues (SSAs), particularly those
      with multireceptor activity. We present data from the PRIMARYS study on the
      impact of the SSA lanreotide, associated with tumour volume and hormonal
      improvements, on glucose and other metabolic parameters in acromegaly. DESIGN:
      PRIMARYS was a 48-week open-label single-arm phase 3b study of lanreotide autogel
      120 mg/4 weeks. A priori and post hoc metabolic profile data are reported for the
      overall population, patients with/without diabetes and patients achieving/not
      achieving hormonal control. PATIENTS: Treatment-naive adults with pituitary
      macroadenoma, mean growth hormone >1 MUg/l and elevated insulin-like growth
      factor-1 levels (n = 90). MEASUREMENTS: Glycaemic parameters [glycated
      haemoglobin (HbA1c ) and fasting plasma glucose (FPG) levels] assessed at
      baseline and weeks 12, 24 and 48. Lipid-profile data (triglycerides, total
      cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein
      cholesterol) collected at baseline and study end. RESULTS: In patients with
      diabetes (n = 24), HbA1c showed a clinically relevant decrease during treatment
      [mean change from baseline to week 48, -1.44% (95% CI: -2.52, -0.36)]. In the
      overall population, in patients without diabetes, or in patients with/without
      hormonal control, HbA1c did not significantly change by week 48. Mean FPG levels
      showed no significant change by week 48 in all populations. Individually,
      increases and decreases in glycaemic parameters affected some patients in all
      populations. Glycaemic status as a composite measure of HbA1c and FPG
      (classification as normal, mild or diabetic) was stable from baseline to study
      end in most patients (overall, 70%; patients with diabetes, 50%; patients without
      diabetes, 76%), but worsened by week 48 in nine (15%) patients [seven (50%) with
      diabetes at baseline] and improved in nine (15%) patients (none with diabetes).
      Changes in lipid profiles were not considered clinically meaningful. CONCLUSIONS:
      Glucose and lipid levels were not detrimentally affected in most patients, while
      only a relatively small proportion showed deterioration in glucose control.

PMID- 27874200
TI  - Two patients with GMPPB mutation: The overlapping phenotypes of limb-girdle
      myasthenic syndrome and limb-girdle muscular dystrophy dystroglycanopathy.
AB  - INTRODUCTION: Mutations in the guanosine diphosphate-mannose pyrophosphorylase-B
      gene (GMPPB) have been identified in congenital muscular dystrophies, limb-girdle
      muscular dystrophy (LGMD2T), and congenital myasthenic syndromes (CMSs); overall,
      41 patients have been described. METHODS: Two patients presented with a
      myasthenic syndrome (patient 1; 74 years old) and rhabdomyolysis (patient 2; 23
      years old). Examinations included repetitive nerve stimulation, muscle biopsy and
      whole-body MRI (WBMRI); next generation sequencing facilitated diagnosis.
      RESULTS: We identified the following GMPPB mutations: c.79G>C/c.859C>T in the 23
      year-old man with LGMD2T-phenotype and c.79G>C homozygosity in the 74-year-old
      woman with CMS phenotype. WBMRI showed fatty degeneration of paraspinal, thigh
      adductor, and calf muscles in patient 1 and edematous changes of the soleus
      muscle in patient 2. CONCLUSIONS: This case of c.79G>C homozygosity causing a
      mild, late-onset CMS phenotype, confirms the mild nature of this common mutation.
      The descriptions of these 2 new GMPPB cases add to the knowledge regarding this
      recently discovered, heterogeneous disease. Muscle Nerve 56: 334-340, 2017.

PMID- 27874201
TI  - Follicular Psoriasis: Differentiation from Pityriasis Rubra Pilaris-An
      Illustrative Case and Review of the Literature.
AB  - The follicular presentation of psoriasis is a well-described but uncommon
      variant. In some cases, follicular psoriasis may clinically and
      histopathologically mimic pityriasis rubra pilaris. There are several reports
      discussing the resemblance of widespread follicular psoriasis in children to
      pityriasis rubra pilaris. We describe a case of follicular psoriasis in a 16-year
      old black girl with acrally distributed follicular hyperkeratotic papules with
      associated keratoderma of her plantar surfaces resembling pityriasis rubra
      pilaris.

PMID- 27874202
TI  - Defining pollen exposure times for clinical trials of allergen immunotherapy for
      pollen-induced rhinoconjunctivitis - an EAACI position paper.
AB  - BACKGROUND: Clinical efficacy of pollen allergen immunotherapy (AIT) has been
      broadly documented in randomized controlled trials. The underlying clinical
      endpoints are analysed in seasonal time periods predefined based on the
      background pollen concentration. However, any validated or generally accepted
      definition from academia or regulatory authorities for this relevant pollen
      exposure intensity or period of time (season) is currently not available.
      Therefore, this Task Force initiative of the European Academy of Allergy and
      Clinical Immunology (EAACI) aimed to propose definitions based on expert
      consensus. METHODS: A Task Force of the Immunotherapy and Aerobiology and
      Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure
      in the context of defining relevant time intervals for evaluation of efficacy in
      AIT trials. Underlying principles in measuring pollen exposure and associated
      methodological problems and limitations were considered to achieve a consensus.
      RESULTS: The Task Force achieved a comprehensive position in defining pollen
      exposure times for different pollen types. Definitions are presented for 'pollen
      season', 'high pollen season' (or 'peak pollen period') and 'high pollen days'.
      CONCLUSION: This EAACI position paper provides definitions of pollen exposures
      for different pollen types for use in AIT trials. Their validity as standards
      remains to be tested in future studies.

PMID- 27874203
TI  - Multifocal Congenital Hemangiopericytoma.
AB  - Congenital hemangiopericytoma (HPC) is a rare mesenchymal tumor with less
      aggressive behavior and a more favorable prognosis than similar tumors in adults.
      Multifocal presentation is even less common than isolated HPC and hence its
      clinical and histologic recognition may be challenging. A newborn infant with
      multifocal congenital HPC causing severe deformity but with a favorable outcome
      after chemotherapy and surgical removal is reported.

PMID- 27874204
TI  - Field-testing the new anaphylaxis' classification for the WHO International
      Classification of Diseases-11 revision.
AB  - BACKGROUND: To consolidate the new classification model addressed to the allergic
      and hypersensitivity conditions according to the International Classification of
      Diseases (ICD)-11 revision timeline, we here propose real-life application of
      quality assurance methodology to evaluate sensitivity and accuracy of the
      'Anaphylaxis' subsection. METHODS: We applied field-testing methodology by
      analysing all the consecutive inpatients' files documented as allergies from the
      University Hospital of Montpellier electronic database for the period of 1 year.
      The files clinically validated as being anaphylaxis were manually blind-coded
      under ICD-10 and current ICD-11 beta draft. The correspondence of coding and the
      impressions regarding sensibility were evaluated. RESULTS: From all 2318 files
      related to allergic or hypersensitivity conditions, 673 had some of the
      anaphylaxis ICD-10 codes; 309 files (46%) from 209 patients had anaphylaxis and
      allergic or hypersensitivity comorbidities description. The correspondence
      between the two coders was perfect for 162 codes from all 309 entities (52.4%)
      (Cohen-kappa value 0.63) with the ICD-10 and for 221 codes (71.5%) (Cohen-kappa
      value 0.77) with the ICD-11. There was a high agreement regarding sensibility of
      the ICD-11 usability (Cohen-kappa value 0.75). CONCLUSION: We here propose the
      first attempt of real-life application to validate the new ICD-11 'Anaphylaxis'
      subsection. Clearer was the improvement in accuracy reaching 71.5% of agreement
      when ICD-11 was used. By allowing all the relevant diagnostic terms for
      anaphylaxis to be included into the ICD-11 framework, WHO has recognized their
      importance not only to clinicians but also to epidemiologists, statisticians,
      healthcare planners and other stakeholders.

PMID- 27874205
TI  - Blau Syndrome: A Systemic Granulomatous Disease of Cutaneous Onset and Phenotypic
      Complexity.

PMID- 27874206
TI  - Spitz Nevi and Other Spitzoid Neoplasms in Children: Overview of Incidence Data
      and Diagnostic Criteria.
AB  - Spitz nevi are benign melanocytic neoplasms characterized by epithelioid or
      spindle melanocytes or both. In some rare cases their presentation overlaps with
      the clinical and histopathologic features of malignant melanoma, so a
      differential diagnosis can be difficult to make. Intermediate forms between Spitz
      nevi and malignant melanoma, with unpredictable behavior, have been called
      atypical Spitz tumors. A literature search was performed to review the clinical,
      dermoscopic, genetic, and histopathologic aspects of spitzoid tumors. Spitz nevi
      mainly occur in children, with no predilection for sex, and in young women.
      Common sites are the head and lower arms, where Spitz nevi present as pink
      nodules or hyperpigmented plaques. Spitzoid lesions may have diverse dermoscopic
      patterns: vascular, starburst, globular, atypical, reticular, negative
      homogeneous, or targetoid. The management of spitzoid lesions can be invasive or
      conservative; surgical excision is usually reserved for those with doubtful
      features, whereas clinical and dermoscopic follow-up is preferred for typical
      pediatric Spitz nevi. The role of sentinel lymph node biopsy in atypical Spitz
      tumors is debated. Immunohistochemistry and new molecular techniques such as
      comparative genomic hybridization, polymerase chain reaction, and fluorescence in
      situ hybridization offer new diagnostic perspectives, investigating genetic
      alterations that are specific for malignant melanoma or for Spitz nevi.

PMID- 27874207
TI  - Congenital high airway obstruction syndrome (CHAOS) associated with cervical
      myelomeningocele.
AB  - Congenital high airway obstruction syndrome (CHAOS) is a rare and potentially
      fatal entity resulting from complete or near complete developmental airway
      obstruction. Although most reported cases of CHAOS are sporadic, the condition
      may also be associated with certain syndromes and a variety of cervical masses.
      Meningocele and myelomeningocele have not yet been reported in association with
      CHAOS. We describe the typical constellation of sonographic findings in a case of
      early diagnosis of CHAOS associated with cervical myelomeningocele. (c) 2016
      Wiley Periodicals, Inc. J Clin Ultrasound 45:507-510, 2017.

PMID- 27874208
TI  - Steady-state protein focusing in carrier ampholyte based isoelectric focusing:
      Part I-Analytical solution.
AB  - The determination of an analytical solution to find the steady-state protein
      concentration distribution in IEF is very challenging due to the nonlinear
      coupling between mass and charge conservation equations. In this study,
      approximate analytical solutions are obtained for steady-state protein
      distribution in carrier ampholyte based IEF. Similar to the work of Svensson, the
      final concentration profile for proteins is assumed to be Gaussian, but
      appropriate expressions are presented in order to obtain the effective electric
      field and pH gradient in the focused protein band region. Analytical results are
      found from iterative solutions of a system of coupled algebraic equations using
      only several iterations for IEF separation of three plasma proteins: albumin,
      cardiac troponin I, and hemoglobin. The analytical results are compared with
      numerically predicted results for IEF, showing excellent agreement. Analytically
      obtained electric field and ionic conductivity distributions show significant
      deviation from their nominal values, which is essential in finding the protein
      focusing behavior at isoelectric points. These analytical solutions can be used
      to determine steady-state protein concentration distribution for experiment
      design of IEF considering any number of proteins and ampholytes. Moreover, the
      model presented herein can be used to find the conductivity, electric field, and
      pH field.

PMID- 27874209
TI  - Airway eosinophil migration into lymph nodes in mice depends on leukotriene C4.
AB  - BACKGROUND: We previously demonstrated in mice that airway eosinophils traffic
      from the airway lumen into lung-draining paratracheal lymph nodes. However,
      mechanisms whereby eosinophils traverse from the lungs and home to paratracheal
      lymph nodes remain unclear. We investigated roles of cysteinyl leukotrienes in
      mediating eosinophil trafficking from lungs to paratracheal lymph nodes. METHODS:
      The expression of CCR7 was determined by flow cytometry. Transwell assays were
      used to test chemotactic responses of leukotriene C4 synthase-deficient and
      control airway eosinophils to the chemokine CCL19 ex vivo. Eosinophils from the
      spleens of IL-5 transgenic mice, fluorescently labeled ex vivo, were
      intratracheally injected into ovalbumin-sensitized and ovalbumin aerosol
      challenged leukotriene C4 synthase-deficient and control mice. Eosinophils were
      identified by microscopy and flow cytometry in the lungs and paratracheal lymph
      nodes. RESULTS: Mouse eosinophils expressed CCR7, the receptor for CCL19, and
      responded chemotactically to CCL19. Leukotriene C4 synthase-deficient eosinophils
      exhibited impaired chemotaxis to CCL19 that was restored by exogenous leukotriene
      C4 . The migration of intratracheally injected eosinophils into paratracheal
      lymph nodes from distal alveolar lung was diminished in leukotriene C4 synthase
      deficient mice compared with wild-type mice, with increased retention of
      eosinophils in the lungs of leukotriene C4 synthase-deficient mice. Exogenous
      administration of leukotriene C4 restored trafficking of eosinophils to
      paratracheal lymph nodes in leukotriene C4 synthase-deficient mice. CONCLUSIONS:
      Our findings that cysteinyl leukotrienes are involved in regulating airway and
      lung eosinophil migration into paratracheal lymph nodes identify previously
      unrecognized roles for the cysteinyl leukotrienes in regulating the pulmonary
      trafficking of eosinophils in experimental allergic asthma.

PMID- 27874211
TI  - Characteristics of volatile organic compounds produced from five pathogenic
      bacteria by headspace-solid phase micro-extraction/gas chromatography-mass
      spectrometry.
AB  - The characteristics of volatile compounds from five different bacterial species,
      Escherichia coli O157:H7, Salmonella Enteritidis, Shigella flexneri,
      Staphylococcus aureus, and Listeria monocytogenes, growing, respectively, in
      trypticase soy broth were monitored by headspace solid-phase micro-extraction/gas
      chromatography-mass spectrometry. The results showed that most volatile organic
      compounds (VOCs) of five pathogens started to increase after the sixth to tenth
      hour. Methyl ketones and long chain alcohols were representative volatiles for
      three Gram-negative bacteria. The especially high production of indole was
      characterized to E. coli O157:H7. The production of 3-hydroxy-2-butanone was
      indicative of the presence of two Gram-positive bacteria. Both 3-methyl-butanoic
      acid and 3-methyl-butanal were unique biomarkers for S. aureus. The population
      dynamics of individual pathogen could be monitored using the accumulation of VOCs
      correlated with its growth. And these five pathogens could be distinguishable
      though principle component analysis of 18 volatile metabolites. Moreover, the
      mixed culture of S. aureus and E. coli O157:H7 was also investigated. The levels
      of 3-methyl-butanal and 3-methyl-butanoic acid were largely reduced; while the
      level of indole almost unchanged and correlated with E. coli O157:H7 growth very
      well. The characteristics of volatiles from the five foodborne pathogens could
      lay a fundamental basis for further research into pathogen contamination control
      by detecting volatile signatures of pathogens.

PMID- 27874210
TI  - Cost effectiveness of using cognitive screening tests for detecting dementia and
      mild cognitive impairment in primary care.
AB  - INTRODUCTION: We estimated the cost effectiveness of different cognitive
      screening tests for use by General Practitioners (GPs) to detect cognitive
      impairment in England. METHODS: A patient-level cost-effectiveness model was
      developed using a simulated cohort that represents the elderly population in
      England (65 years and older). Each patient was followed over a lifetime period.
      Data from published sources were used to populate the model. The costs include
      government funded health and social care, private social care and informal care.
      Patient health benefit was measured and valued in Quality Adjusted Life Years
      (QALYs). RESULTS: Base-case analyses found that adopting any of the three
      cognitive tests (Mini-Mental State Examination, 6-Item Cognitive Impairment Test
      or GPCOG (General Practitioner Assessment of Cognition)) delivered more QALYs for
      patients over their lifetime and made savings across sectors including
      healthcare, social care and informal care compared with GP unassisted judgement.
      The benefits were due to early access to medications. Among the three cognitive
      tests, adopting the GPCOG was considered the most cost-effective option with the
      highest Incremental Net Benefit (INB) at the threshold of L30 000 per QALY from
      both the National Health Service and Personal Social Service (NHS PSS)
      perspective (L195 034 per 1000 patients) and the broader perspective that
      includes private social care and informal care (L196 251 per 1000 patients).
      Uncertainty was assessed in both deterministic and probabilistic sensitivity
      analyses. CONCLUSIONS: Our analyses indicate that the use of any of the three
      cognitive tests could be considered a cost-effective strategy compared with GP
      unassisted judgement. The most cost-effective option in the base-case was the
      GPCOG. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27874213
TI  - Questioning the Clinical Utility of Exome Sequencing in Developing Countries.
AB  - The availability of whole-exome sequencing has revolutionized the study of
      genetic disease in recent years, particularly in dermatology, where clinical
      phenotypes are readily recognized. As this technology becomes increasingly
      affordable and accessible, questions are emerging regarding the clinical and
      ethical responsibilities of physicians who determine variants underlying disease,
      especially with regard to children, for whom treatment may be warranted and
      clinical course improved based on a known genotype. These responsibilities are
      accentuated in the developing countries, which harbor most consanguineous
      populations and thus bear the brunt of monogenic genodermatoses. Although many
      genetic disorders are identified in these populations, limited educational and
      clinical infrastructure rarely offers opportunities to improve the course of
      disease. Here we report a genetic study that illustrates these challenges.

PMID- 27874212
TI  - Dorsal column myelopathy after intrathecal chemotherapy for leukemia.
AB  - Intrathecal chemotherapy with methotrexate, a folate antagonist, is widely used
      to treat central nervous system malignancies. The mechanisms underlying
      methotrexate-induced neurotoxicity are unclear but may be related to increased
      homocysteine levels. Intrathecal methotrexate-induced myelopathy mimicking
      subacute combined degeneration, with normal B12 levels, has been documented. We
      examined treatment and magnetic resonance imaging (MRI) characteristics of 13
      patients with leukemia who received intrathecal methotrexate and developed
      urinary and bowel incontinence, ascending motor weakness, and sensory loss with
      dorsal column hyperintensity on MRI between 2000 and 2016. Cerebrospinal fluid
      evaluation was negative for leukemia in all patients and positive for elevated
      protein in 12 patients. Seven of eight patients with available data had reduced
      serum folate, increased serum homocysteine, or both, implicating methotrexate as
      the cause of neurotoxicity. Autopsy of one patient revealed loss of myelinated
      axons in the posterior columns. These findings suggest that methotrexate
      neurotoxicity may be mediated by folate antagonism. Awareness and a high index of
      suspicion of these characteristic clinical and radiographic features in patients
      who develop myelopathy after intrathecal methotrexate may help to avoid
      additional neurotoxic therapy in such patients.

PMID- 27874214
TI  - Surfactant-Free Aqueous Synthesis of Pure Single-Crystalline SnSe Nanosheet
      Clusters as Anode for High Energy- and Power-Density Sodium-Ion Batteries.
AB  - SnSe with 3D hierarchical nanostructure composed of interconnected single-crystal
      SnSe nanosheets is synthesized via a fast and effective strategy. Unexpectedly,
      when used as the anode material for Na-ion batteries (NIBs), the SnSe exhibits a
      high capacity (738 mA h g-1 ), superior rate capability (40 A g-1 ), and high
      energy density in a full cell. These results provide the possibility of SnSe use
      as NIBs anodes.

PMID- 27874215
TI  - Predicting Follow-up Outcomes in Emotionally Focused Couple Therapy: The Role of
      Change in Trust, Relationship-Specific Attachment, and Emotional Engagement.
AB  - Emotionally Focused Couple Therapy (EFT), an evidence-based couple therapy
      (Johnson, Hunsley, Greenberg, & Schindler, 1999), strives to foster lasting
      change through the creation of secure attachment bonds in distressed couples.
      Although studies have demonstrated lasting change in follow-up (Wiebe et al., in
      press), research is needed to investigate predictors of long-term outcomes. Our
      goal was to investigate predictors of long-term outcomes in relationship
      satisfaction. Relationship satisfaction was assessed across 24 months in a sample
      of 32 couples who received an average of 21 EFT sessions. Decreases in attachment
      avoidance were most predictive of higher relationship satisfaction across follow
      up. These findings support the theoretical assumption that EFT helps couples
      foster lasting change in relationship satisfaction through the facilitation of
      secure attachment bonds.

PMID- 27874216
TI  - Complementary and Alternative Therapies Used by Patients of Pediatric Dermatology
      Outpatient Clinics in Turkey: A Multicenter Study.
AB  - BACKGROUND: The aim of this study was to determine the frequency of complementary
      and alternative medicine (CAM) methods used in children and adolescents with
      chronic skin diseases, which methods parents prefer, and to what extent these
      methods are useful. MATERIAL AND METHODS: This cross-sectional study was
      conducted between June and November 2014 in patients with chronic skin diseases
      attending the outpatient pediatric dermatology clinics of three hospitals in
      Turkey. Data were collected using self-administered questionnaires from the
      parents of the patients. RESULTS: A total of 307 patients were included in the
      study, 168 (54.7%) of whom were female and 139 (45.3%) male. The mean age was
      12.3 +/- 4.3 years. Eighty of the children (26.1%) had used CAM methods in the
      previous year. Longer disease duration and having a father with at least a
      university degree were highly associated with CAM use (p < 0.05). The most used
      method was herbal remedies available at home. Most patients used CAM methods to
      support the primary treatment given by their dermatologists. Only eight CAM users
      (2.6%) reported any side effects. Thirty-nine (48.8%) did not mention CAM use to
      their doctors. The overall satisfaction rate was 4.5 +/- 3.1 on a 10-point rating
      scale. CONCLUSION: CAM use rates are high in children with chronic skin problems,
      and parents generally prefer herbal treatments. Satisfaction with the results of
      CAM use is moderate. Parents generally do not share CAM use information with
      their doctors unless they are asked.

PMID- 27874217
TI  - Atomically Thin Hexagonal Boron Nitride Nanofilm for Cu Protection: The
      Importance of Film Perfection.
AB  - Outstanding protection of Cu by high-quality boron nitride nanofilm (BNNF) 1-2
      atomic layers thick in salt water is observed, while defective BNNF accelerates
      the reaction of Cu toward water. The chemical stability, insulating nature, and
      impermeability of ions through the BN hexagons render BNNF a great choice for
      atomic-scale protection.

PMID- 27874218
TI  - Supplementation of distiller's grains during late gestation in beef cows
      consuming low-quality forage decreases uterine, but not mammary, blood flow.
AB  - Positive effects have been observed in offspring from beef cows supplemented with
      corn dried distillers grain with solubles (DDGS) during late gestation. The
      hypothesis of this study was that late gestational DDGS supplementation to beef
      cows would increase blood flow (BF) to the gravid uterus and mammary gland thus
      impacting birthweight and post-natal growth of the offspring. Experiment 1
      investigated mammary gland BF in multiparous cows during late pregnancy. Beef
      cows were fed a control (CON1) diet of low-quality hay (n = 5) or a supplement
      diet (SUP1) of low-quality hay with DDGS [1.7 g/kg of body weight (BW); n = 6].
      In Experiment 2, multiparous late pregnant beef cows were fed either a control
      (CON2) diet of a low-quality hay (n = 4) or a supplement diet (SUP2) of low
      quality hay with DDGS (1.7 g/kg of BW; n = 5). Uterine and mammary gland BF were
      recorded every 21 days during late gestation. In Experiment 1, there were no
      effects of diet or day on mammary gland hemodynamics. In Experiment 2, total and
      ipsilateral uterine BF was less (p <= 0.04) in SUP2 vs. CON2 cows and similar BF
      to contralateral horns. Mammary gland BF was unaltered by maternal
      supplementation. Even when measured in two different years in two different
      environments, mammary gland BF remained unaltered to DDGS supplementation.
      Investigations on the mechanism that may impact uterine BF during late gestation
      remain to be known.

PMID- 27874219
TI  - Sonographic appearance of pyomyositis of the sternocleidomastoid muscle: A case
      report.
AB  - Pyomyositis in the neck has rarely been described. We present the sonographic
      findings in a case of pyomyositis of the sternocleidomastoid muscle. A 62-year
      old man with poorly controlled diabetes presented with an induration of the neck
      and fever. On gray-scale sonography, a part of the sternocleidomastoid muscle
      appeared swollen and contained irregularly shaped hypoechoic areas. Power Doppler
      imaging showed increased vascularity in the muscle. Sonographic-guided aspiration
      confirmed abscesses in the sternocleidomastoid muscle. Surgical drainage was
      successfully performed along with antibiotic treatment. (c) 2016 Wiley
      Periodicals, Inc. J Clin Ultrasound 45:520-523, 2017.

PMID- 27874220
TI  - Shape-Persistent Graphite Replica of Metal Wires.
AB  - A facile one-step procedure for a template-assisted fabrication of hollow carbon
      tubes is reported, using organic halides as the carbon source. The shape
      persistent tubes are obtained with arbitrary shapes as hollow replicas of the
      metal template. They feature a high quality of graphite, and a high conductivity
      of 1.31 +/- 0.05 . 106 S.m-1 .

PMID- 27874221
TI  - Ultrasound-guided core needle biopsy of cervical lymph nodes in the diagnosis of
      toxoplasmosis.
AB  - BACKGROUND: Our study investigates whether the histopathological features of
      toxoplasmic lymphadenitis (TL), specifically noncaseating microgranuloma and
      follicular hyperplasia, can be obtained by sonographic-guided core needle biopsy
      (CNB) of cervical lymph nodes. METHODS: Thirty-two patients seen from June 2014
      to March 2015 were positive for toxoplasma immunoglobulin M antibody. Among those
      patients, 21 underwent CNB of a cervical lymph node and were enrolled in this
      study. The pathologic findings were reviewed. RESULTS: Twenty-nine lymph nodes in
      21 patients were sampled. Eighteen of the 21 (86%) patients had a microgranuloma
      without caseating necrosis or giant cells, and all 21 (100%) patients had
      follicular hyperplasia. CONCLUSIONS: The histologic findings of TL were detected
      by sonographic-guided CNB, which can be used as part of the first line of
      investigation in patients with unexplained cervical adenopathy. (c) 2016 Wiley
      Periodicals, Inc. J Clin Ultrasound 45:192-196, 2017.

PMID- 27874222
TI  - Piezophototronic-Effect-Enhanced Electrically Pumped Lasing.
AB  - This study demonstrates significant improvements of ZnO nanowire lasers by the
      piezophototronic effect. The laser output power can be enhanced by a factor of
      4.96, and the threshold voltage can be decreased from 48 to 20 V by applying
      pressure. The mechanism of the improved performance can be attributed to the
      enhanced carrier injection and recombination due to the piezophototronic effect.

PMID- 27874223
TI  - Metal-Semiconductor Phase-Transition in WSe2(1-x) Te2x Monolayer.
AB  - A metal-semiconductor phase transition in a ternary transition metal
      dichalcogenide (TMD) monolayer is achieved by alloying Te into WSe2 (WSe2(1-x)
      Te2x , where x = 0%-100%). The optical bandgaps of the WSe2(1-x) Te2x monolayer
      can be tuned from 1.67 to 1.44 eV (2H semiconductor) and drops to 0 eV (1Td
      metal), which opens up an exciting opportunity in functional
      electronic/optoelectronic devices.

PMID- 27874224
TI  - Multiple transporters are involved in natamycin efflux in Streptomyces
      chattanoogensis L10.
AB  - Antibiotic-producing microorganisms have evolved several self-resistance
      mechanisms to prevent auto-toxicity. Overexpression of specific transporters to
      improve the efflux of toxic antibiotics has been found one of the most important
      and intrinsic resistance strategies used by many Streptomyces strains. In this
      work, two ATP-binding cassette (ABC) transporter-encoding genes located in the
      natamycin biosynthetic gene cluster, scnA and scnB, were identified as the
      primary exporter genes for natamycin efflux in Streptomyces chattanoogensis L10.
      Two other transporters located outside the cluster, a major facilitator
      superfamily transporter Mfs1 and an ABC transporter NepI/II were found to play a
      complementary role in natamycin efflux. ScnA/ScnB and Mfs1 also participate in
      exporting the immediate precursor of natamycin, 4,5-de-epoxynatamycin, which is
      more toxic to S. chattanoogensis L10 than natamycin. As the major complementary
      exporter for natamycin efflux, Mfs1 is up-regulated in response to intracellular
      accumulation of natamycin and 4,5-de-epoxynatamycin, suggesting a key role in the
      stress response for self-resistance. This article discusses a novel antibiotic
      related efflux and response system in Streptomyces, as well as a self-resistance
      mechanism in antibiotic-producing strains.

PMID- 27874225
TI  - Networking Pyrolyzed Zeolitic Imidazolate Frameworks by Carbon Nanotubes Improves
      Conductivity and Enhances Oxygen-Reduction Performance in Polymer-Electrolyte
      Membrane Fuel Cells.
AB  - A high-performance nonprecious-metal oxygen-reduction electrocatalyst is prepared
      via in situ growth of bimetallic zeolitic imidazolate frameworks on multiwalled
      carbon nanotubes (CNTs) followed by adsorption of furfuryl alcohol and pyrolysis.
      The networking boosts the conductivity and performance in a polymer electrolyte
      membrane fuel cell, yielding a maximal power density of 820 mW cm-2 .

PMID- 27874226
TI  - Getting the Most out of Solar Irradiation: Efficient Use of Polychromatic Light
      for Water Splitting.
AB  - To increase the fraction of utilizable polychromatic light, a new reactor concept
      was developed and manufactured by using rapid prototyping technologies.
      Investigation of the prototypes revealed enhancements of the photocurrent by up
      to one order of magnitude, when TiO2 was used as the photoanode in combination
      with commercially available photovoltaic cells. The reported concept is scalable
      and an easy transfer to technical scale is expected from a technological as well
      as an economical perspective. Experimental results underline the conclusion that
      to achieve efficient overall use of solar irradiation both the material as well
      as the reactor/process must be considered. Combining these complementary
      approaches allows largest possible optimization potential. With respect to
      ongoing research, the concept also breaks ground for the development of
      catalysts.

PMID- 27874227
TI  - Csx WO3 Nanorods Coated with Polyelectrolyte Multilayers as a Multifunctional
      Nanomaterial for Bimodal Imaging-Guided Photothermal/Photodynamic Cancer
      Treatment.
AB  - Csx WO3 nanorods coated with polyelectrolyte multilayers are developed as "four
      in-one" multifunctional nanomaterials with significant potential for computed
      tomography/photoacoustic tomography bimodal imaging-guided
      photothermal/photodynamic cancer treatment.

PMID- 27874228
TI  - Dually Ordered Porous TiO2 -rGO Composites with Controllable Light Absorption
      Properties for Efficient Solar Energy Conversion.
AB  - Quadruple-layered TiO2 films with controllable macropore size are prepared via a
      confinement self-assembly method. The inverse opal structure with ordered
      mesoporous (IOM) presents unique light reflection and scattering ability with
      different wavelengths. Cyan light (400-600 nm) is reflected and scattered by IOM
      195, which is in accord with N719 absorption spectra. By manipulating the
      macropore size, different light responses are obtained.

PMID- 27874229
TI  - Exopolysaccharides promote Myxococcus xanthus social motility by inhibiting
      cellular reversals.
AB  - The biofilm-forming bacterium Myxococcus xanthus moves on surfaces as structured
      swarms utilizing type IV pili-dependent social (S) motility. In contrast to
      isolated cells that reverse their moving direction frequently, individual cells
      within swarms rarely reverse. The regulatory mechanisms that inhibit cellular
      reversal and promote the formation of swarms are not well understood. Here we
      show that exopolysaccharides (EPS), the major extracellular components of M.
      xanthus swarms, inhibit cellular reversal in a concentration-dependent manner.
      Thus, individual wild-type cells reverse less frequently in swarms due to high
      local EPS concentrations. In contrast, cells defective in EPS production hyper
      reverse their moving direction and show severe defects in S-motility.
      Surprisingly, S-motility and wild-type reversal frequency are restored in double
      mutants that are defective in both EPS production and the Frz chemosensory
      system, indicating that EPS regulates cellular reversal in parallel to the Frz
      pathway. Here we clarify that besides functioning as the structural scaffold in
      biofilms, EPS is a self-produced signal that coordinates the group motion of the
      social bacterium M. xanthus.

PMID- 27874230
TI  - TiO2 -Supported Re as a General and Chemoselective Heterogeneous Catalyst for
      Hydrogenation of Carboxylic Acids to Alcohols.
AB  - TiO2 -supported Re, Re/TiO2 , was found to promote selective hydrogenation of
      carboxylic acids having aromatic and aliphatic moieties to the corresponding
      alcohols. Re/TiO2 showed superior results compared to other transition-metal
      loaded TiO2 and supported Re catalysts for selective hydrogenation of 3
      phenylpropionic acid. 3-phenylpropanol was produced in 97 % yield under mild
      conditions (5 MPa H2 at 140  degrees C). Contrary to typical heterogeneous
      catalysts, Re/TiO2 does not lead to the formation of dearomatized byproducts. The
      catalyst is recyclable and shows a wide substrate scope in the synthesis of
      alcohols (22 examples; up to 97 % isolated yield).

PMID- 27874231
TI  - Stability of domain 4 of the anthrax toxin protective antigen and the effect of
      the VWA domain of CMG2 on stability.
AB  - The major immunogenic component of the current anthrax vaccine, anthrax vaccine
      adsorbed (AVA) is protective antigen (PA). We have shown recently that the
      thermodynamic stability of PA can be significantly improved by binding to the Von
      Willebrand factor A (VWA) domain of capillary morphogenesis protein 2 (CMG2), and
      improvements in thermodynamic stability may improve storage and long-term
      stability of PA for use as a vaccine. In order to understand the origin of this
      increase in stability, we have isolated the receptor binding domain of PA, domain
      4 (D4), and have studied the effect of the addition of CMG2 on thermodynamic
      stability. We are able to determine a binding affinity between D4 and CMG2 (~300
      nM), which is significantly weaker than that between full-length PA and CMG2 (170
      300 pM). Unlike full-length PA, we observe very little change in stability of D4
      on binding to CMG2, using either fluorescence or 19 F-NMR experiments. Because in
      previous experiments we could observe a stabilization of both domain 4 and domain
      2, the mechanism of stabilization of PA by CMG2 is likely to involve a mutual
      stabilization of these two domains.

PMID- 27874232
TI  - Dynamic Self-Assembly Encodes A Tri-stable Au-TiO2 Photocatalyst.
AB  - A tri-stable switchable catalyst is encoded by pH-controlled dynamic self
      assembly of gold and TiO2 nanoparticles (NPs). Through precise adjustment of the
      integrated dynamic covalent and noncovalent self-assembly process of the two
      types of nanoparticles, the photocatalytic activity of the hybrid system is
      modulated by switching pH conditions between tri-stable "highly active",
      "active", and "inactive" states.

PMID- 27874234
TI  - Bioorthogonal Probes for the Study of MDM2-p53 Inhibitors in Cells and
      Development of High-Content Screening Assays for Drug Discovery.
AB  - To study the behavior of MDM2-p53 inhibitors in a disease-relevant cellular
      model, we have developed and validated a set of bioorthogonal probes that can be
      fluorescently labeled in cells and used in high-content screening assays. By
      using automated image analysis with single-cell resolution, we could visualize
      the intracellular target binding of compounds by co-localization and quantify
      target upregulation upon MDM2-p53 inhibition in an osteosarcoma model.
      Additionally, we developed a high-throughput assay to quantify target occupancy
      of non-tagged MDM2-p53 inhibitors by competition and to identify novel chemical
      matter. This approach could be expanded to other targets for lead discovery
      applications.

PMID- 27874235
TI  - Extending the Life of Lithium-Based Rechargeable Batteries by Reaction of Lithium
      Dendrites with a Novel Silica Nanoparticle Sandwiched Separator.
AB  - A reaction-protective separator that slows the growth of lithium dendrites
      penetrating into the separator is produced by sandwiching silica nanoparticles
      between two polymer separators. The reaction between lithium dendrites and silica
      nanoparticles consumes the dendrites and can extend the life of the battery by
      approximately five times.

PMID- 27874233
TI  - Induction of hepatocyte-like cells from human umbilical cord-derived mesenchymal
      stem cells by defined microRNAs.
AB  - Generating functional hepatocyte-like cells (HLCs) from mesenchymal stem cells
      (MSCs) is of great urgency for bio-artificial liver support system (BALSS).
      Previously, we obtained HLCs from human umbilical cord-derived MSCs by
      overexpressing seven microRNAs (HLC-7) and characterized their liver functions in
      vitro and in vivo. Here, we aimed to screen out the optimal miRNA candidates for
      hepatic differentiation. We sequentially removed individual miRNAs from the pool
      and examined the effect of transfection with remainder using RT-PCR, periodic
      acid-Schiff (PAS) staining and low-density lipoprotein (LDL) uptake assays and by
      assessing their function in liver injury models. Surprisingly, miR-30a and miR
      1290 were dispensable for hepatic differentiation. The remaining five miRNAs (miR
      122, miR-148a, miR-424, miR-542-5p and miR-1246) are essential for this process,
      because omitting any one from the five-miRNA combination prevented hepatic trans
      differentiation. We found that HLCs trans-differentiated from five microRNAs (HLC
      5) expressed high level of hepatic markers and functioned similar to hepatocytes.
      Intravenous transplantation of HLC-5 into nude mice with CCl4 -induced fulminant
      liver failure and acute liver injury not only improved serum parameters and their
      liver histology, but also improved survival rate of mice in severe hepatic
      failure. These data indicated that HLC-5 functioned similar to HLC-7 in vitro and
      in vivo, which have been shown to resemble hepatocytes. Instead of using seven
      miRNA combination, a simplified five-miRNA combination can be used to obtain
      functional HLCs in only 7 days. Our study demonstrated an optimized and efficient
      method for generating functional MSC-derived HLCs that may serve as an attractive
      cell alternative for BALSS.

PMID- 27874236
TI  - On Approaching the Limit of Molecular Magnetic Anisotropy: A Near-Perfect
      Pentagonal Bipyramidal Dysprosium(III) Single-Molecule Magnet.
AB  - We report a monometallic dysprosium complex, [Dy(Ot Bu)2 (py)5 ][BPh4 ] (5), that
      shows the largest effective energy barrier to magnetic relaxation of Ueff
      =1815(1) K. The massive magnetic anisotropy is due to bis-trans-disposed tert
      butoxide ligands with weak equatorial pyridine donors, approaching proposed
      schemes for high-temperature single-molecule magnets (SMMs). The blocking
      temperature, TB  , is 14 K, defined by zero-field-cooled magnetization
      experiments, and is the largest for any monometallic complex and equal with the
      current record for [Tb2 N2 {N(SiMe3 )2 }4 (THF)2 ].

PMID- 27874237
TI  - Tactile stimulation during different developmental periods modifies hippocampal
      BDNF and GR, affecting memory and behavior in adult rats.
AB  - Recent studies have shown that tactile stimulation (TS) in pups is able to
      prevent and/or minimize fear, anxiety behaviors, and addiction to psychostimulant
      drugs in adult rats. In these studies, animals have been exposed to handling from
      postnatal day (PND) 1-21. This study was designed to precisely establish which
      period of preweaning development has a greater influence of TS on neuronal
      development. After birth, male pups were exposed to TS from PND1-7, PND8-14, and
      PND15-21. In adulthood, the different periods of postnatal TS were assessed
      through behavioral, biochemical, and molecular assessments. Animals that received
      TS from PND8-14 showed lower anxiety-like symptoms, as observed by decreased
      anxiety index in elevated plus maze. This same TS period was able to improve
      rats' working memory by increasing the percentage of alternation rate in Y-maze,
      and induce better ability to cope with stressful situations, as showed in the
      defensive burying test by a reduced time of burying behavior. On the other hand,
      animals receiving TS in the first week of life showed longest cumulative burying
      time, which is directly related to increased anxiety-like behavior. Moreover, TS
      from PND8-14 showed lower corticosterone levels and better oxidative status, as
      observed by decreased lipid peroxidation and increased catalase activity in the
      hippocampus. Brain-derived neurotrophic factor (BDNF) immunocontent was increased
      in the hippocampus of animals receiving TS from PND8-14, while glucocorticoid
      receptors immunocontent was decreased in both TS1-7 and TS15-21 , but not TS8-14
      . To the best of our knowledge, this study is the first to show TS can be more
      efficient if applied over a focused period of neonatal development (PND8-14) and
      this beneficial influence can be reflected on reduced emotionality and increased
      ability to address stressful situations in adulthood. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27874238
TI  - Li-Ion Synaptic Transistor for Low Power Analog Computing.
AB  - Nonvolatile redox transistors (NVRTs) based upon Li-ion battery materials are
      demonstrated as memory elements for neuromorphic computer architectures with
      multi-level analog states, "write" linearity, low-voltage switching, and low
      power dissipation. Simulations of backpropagation using the device properties
      reach ideal classification accuracy. Physics-based simulations predict energy
      costs per "write" operation of <10 aJ when scaled to 200 nm * 200 nm.

PMID- 27874239
TI  - Biocatalytic Properties and Structural Analysis of Phloroglucinol Reductases.
AB  - Phloroglucinol reductases (PGRs) are involved in anaerobic degradation in
      bacteria, in which they catalyze the dearomatization of phloroglucinol into
      dihydrophloroglucinol. We identified three PGRs, from different bacterial
      species, that are members of the family of NAD(P)H-dependent short-chain
      dehydrogenases/reductases (SDRs). In addition to catalyzing the reduction of the
      physiological substrate, the three enzymes exhibit activity towards 2,4,6
      trihydroxybenzaldehyde, 2,4,6-trihydroxyacetophenone, and methyl 2,4,6
      trihydroxybenzoate. Structural elucidation of PGRcl and comparison to known SDRs
      revealed a high degree of conservation. Several amino acid positions were
      identified as being conserved within the PGR subfamily and might be involved in
      substrate differentiation. The results enable the enzymatic dearomatization of
      monoaromatic phenol derivatives and provide insight into the functional diversity
      that may be found in families of enzymes displaying a high degree of structural
      homology.

PMID- 27874240
TI  - Three-dimensional printing using open source software and JPEG images from
      optical coherence tomography of an epiretinal membrane patient.

PMID- 27874241
TI  - Living Cationic Polymerization of Vinyl Ethers through a Photoinduced Radical
      Oxidation/Addition/Deactivation Sequence.
AB  - A new photoinitiating system for living cationic polymerization of vinyl ethers
      is reported. In the current approach, visible-light irradiation of dimanganese
      decacarbonyl (Mn2 (CO)10 ) in the presence of an alkyl bromide results in the
      formation of carbon-centered radicals. The photochemically generated radicals
      were then oxidized by diphenyliodonium ions to the corresponding cations. These
      cations can add vinyl ether monomers, which are then rapidly deactivated by the
      bromide anions to give alpha-halide functional end groups. Poly(vinyl ether)
      chains are then grown through successive photoinduced radical
      oxidation/addition/deactivation (PROAD) in a controlled manner. The living nature
      of the system is evaluated through kinetics studies and block copolymer
      formation.

PMID- 27874242
TI  - Template-Framework Interactions in Tetraethylammonium-Directed Zeolite Synthesis.
AB  - Zeolites, having widespread applications in chemical industries, are often
      synthesized using organic templates. These can be cost-prohibitive, motivating
      investigations into their role in promoting crystallization. Herein, the
      relationship between framework structure, chemical composition, synthesis
      conditions and the conformation of the occluded, economical template
      tetraethylammonium (TEA+ ) has been systematically examined by experimental and
      computational means. The results show two distinct regimes of occluded conformer
      tendencies: 1) In frameworks with a large stabilization energy difference, only a
      single conformer was found (BEA, LTA and MFI). 2) In the frameworks with small
      stabilization energy differences (AEI, AFI, CHA and MOR), less than the
      interconversion of TEA+ in solution, a heteroatom-dependent (Al, B, Co, Mn, Ti,
      Zn) distribution of conformers was observed. These findings demonstrate that host
      guest chemistry principles, including electrostatic interactions and coordination
      chemistry, are as important as ideal pore-filling.

PMID- 27874245
TI  - OCT Angiography reveals changes in foveal vessel architecture and foveal flow in
      central serous chorioretinopathy.

PMID- 27874243
TI  - Ultra high performance liquid chromatography-electrospray ionization-tandem mass
      spectrometry and pharmacokinetic analysis of justicidin B and 6'-hydroxy
      justicidin C in rats.
AB  - Arylnaphthalene lignans have attracted considerable interest with the discovery
      of their antineoplastic activities. Two such compounds are justicidin B and 6'
      hydroxy justicidin C, both of which have been isolated from the herb Justicia
      procumbens. We sought to develop and validate a sensitive and accurate, ultra
      high performance liquid chromatography with electrospray ionization tandem mass
      spectrometry method for the structural determination and pharmacokinetics of
      justicidin B and 6'-hydroxy justicidin C. Chromatographic separation was achieved
      on an Agilent 300SB-C18 column using water (0.5% formic acid, 10 mM NH4 COOH)
      methanol as the mobile phase. The plasma samples obtained after oral
      administration of the active extract of Justicia procumbens were successfully
      analyzed with our novel method, thereby demonstrating its sound applicability and
      reliability. The lower limit of quantification for justicidin B and 6'-hydroxy
      justicidin C was 0.50 and 1.00 ng/mL in 50 MUL rat plasma, respectively. The
      elimination half-life and clearance of justicidin B was estimated to be 1.27 +/-
      0.61 h and 5.40 +/- 0.22 L/h/kg while that of 6'-hydroxy justicidin C was 2.07 +/
      0.70 h and 11.84 +/- 1.06 L/h/kg. This newly developed and validated method was
      successfully applied to the quantification and pharmacokinetic study of
      justicidin B and 6'-hydroxy justicidin C in rats.

PMID- 27874244
TI  - Coarctation repair normalizes left ventricular function and aorto-septal angle in
      neonates.
AB  - BACKGROUND AND AIMS: Patients with coarctation of the aorta (CoA) have increased
      left ventricular (LV) afterload that has been shown to impact the LV and
      ascending aortic function. We aimed to examine the effect of coarctation on LV
      function and aorto-septal angle (AoSA) before and after surgical repair. METHODS:
      We retrospectively studied 21 patients with surgically repaired CoA at a median
      age of 9 (2-53) days at three time points: (1) just before intervention, (2) at
      short-term follow-up, and (3) at medium-term follow-up after intervention. AoSA
      was measured from the parasternal long axis view, at three time points during the
      cardiac cycle: (1) end diastole, (2) beginning of systole, and (3) at peak
      ejection in the descending aorta. In addition to conventional LV structure and
      function, global longitudinal strain, and strain rate were measured using STE
      technique and Tomtec software. Three groups of age matched healthy children
      served as controls at each time point. RESULTS: AoSA was significantly wider
      before intervention, in particular at peak ejection in the descending aorta (144
      degrees  +/- 6.4 degrees  vs. 136 degrees  +/- 4.1 degrees ; P < .0001), and
      correlated with CoA pressure gradient. After intervention, AoSA normalized and
      significantly correlated with the increase of LV cavity function and overall LV
      deformation parameters. CONCLUSIONS: AoSA is abnormally wide in neonates with CoA
      and is associated with severity of obstruction, LV dysfunction and compromised LV
      global deformation.

PMID- 27874246
TI  - Predicting the intereye asymmetry in functional and structural damage in glaucoma
      using automated pupillography.
AB  - PURPOSE: To predict the intereye asymmetry in functional (mean deviation, MD on
      visual field, VF) and structural (retinal nerve fibre layer, RNFL and ganglion
      cell complex, GCC thickness on spectral domain optical coherence tomography,
      SDOCT) measurements in glaucoma using the automated pupillography parameters.
      METHODS: Fifty-nine subjects with a diagnosis of either glaucoma or glaucoma
      suspect underwent automated pupillography along with VF and SDOCT examinations.
      Association between pupillography and the absolute intereye difference in MD,
      RNFL and GCC measurements was evaluated using regression analysis after
      accounting for the multicollinearity. RESULTS: Univariate regression analysis
      showed statistically significant associations (p < 0.05) between multiple
      pupillography parameters and the intereye difference in MD, RNFL and GCC
      thickness measurements. Multivariate regression with less strongly correlated
      parameters identified intereye difference in amplitude change (Ac) per cent to be
      the parameter that best predicted the intereye asymmetry in MD (Intereye
      asymmetry in MD = 2.20 + 1.33*intereye difference in Ac per cent, R2  = 0.36),
      RNFL thickness (3.38 + 3.55*intereye difference in Ac per cent, R2  = 0.49) and
      GCC thickness (4.49 + 2.06* intereye difference in Ac per cent, R2  = 0.41).
      Ability of intereye Ac per cent difference to predict intereye asymmetry in MD,
      RNFL and GCC thickness was better in patients with angle closure disease (R2  =
      0.38, 0.79, 0.66, respectively) compared to those with open angles (R2  = 0.25,
      0.15, 0.16, respectively). CONCLUSIONS: Intereye asymmetry in MD, RNFL and GCC
      thickness measurements was best predicted by the intereye difference in Ac per
      cent on automated pupillography. The predicting ability was better in patients
      with angle closure compared to those with open angles.

PMID- 27874247
TI  - The road ahead: Implementing mass cytometry in clinical studies, one cell at a
      time.

PMID- 27874248
TI  - Frequency of IOP measurements and eye check-ups in elderly Finns.

PMID- 27874249
TI  - Role of neural integrators in oculomotor systems: a systematic narrative
      literature review.
AB  - PURPOSE: To evaluate the role of neural integrators (NI) in the oculomotor
      system. METHODS: A literature search was carried out using several electronic
      databases during the months of June 2014 to March 2015. The following keywords
      were used to generate focused results: 'neural integrators', 'gaze-holding',
      'oculomotor integration', 'impaired gaze-holding', 'gaze evoked nystagmus' and
      'gaze dysfunction'. Further materials were found through searching relevant
      articles within reference lists. Seventy-one articles were sourced for this
      review which analysed animal and human subjects and network models; 45 were
      studies of humans, 16 studies of primates, three studies of felines and one study
      from rats and network models. The remaining articles were literature reviews.
      RESULTS: The horizontal and vertical, including torsional, NI are located
      logically in the brainstem, nearby their appropriate target extraocular
      motoneuron nuclei for stable eye position in eccentric position. The nucleus
      prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN) are closely linked
      at the caudal pons and dorsal rostral medulla, integrating horizontal conjugate
      eye movement. The interstitial nucleus of Cajal (INC) integrates vertical and
      torsional eye movement at the upper midbrain. The integrator time constant is
      averaged to 25 seconds in human horizontal and animal vertical NI to perform its
      function. Case reports revealed that dysfunction of horizontal NI also resulted
      in vertical ocular deviations, indicating some overlap of horizontal and vertical
      gaze control. Furthermore, pharmacological inactivation of NI exposed a
      population of inhibitory neurotransmitters that permits its mechanism of action;
      allowing for smooth conjugate movement. CONCLUSIONS: Neural integrators operate
      to integrate eye velocity and eye position information to provide signals to
      extraocular motoneurons to attain and maintain a new position. Therefore, NI
      allow image stabilization during horizontal and vertical eye movements at
      eccentric positions for comfortable single vision.

PMID- 27874250
TI  - Immunosuppression in pediatric liver transplant recipients: Unique aspects.
AB  - Pediatric liver transplantation has experienced improved outcomes over the last
      50 years. This can be attributed in part to establishing optimal use of
      immunosuppressive agents to achieve a balance between minimizing the risks of
      allograft rejection and infection. The management of immunosuppression in
      children is generally more complex and can be challenging when compared with the
      use of these agents in adult liver transplant patients. Physiologic differences
      in children alter the pharmacokinetics of immunosuppressive agents, which affects
      absorption, distribution, metabolism, and drug excretion. Children also have a
      longer expected period of exposure to immunosuppression, which can impact growth,
      risk of infection (bacterial, viral, and fungal), carcinogenesis, and likelihood
      of nonadherence. This review discusses immunosuppressive options for pediatric
      liver transplant recipients and the unique issues that must be addressed when
      managing this population. Further advances in the field of tolerance and
      accommodation are needed to relieve the acute and cumulative burden of chronic
      immunosuppression in children. Liver Transplantation 23 244-256 2017 AASLD.

PMID- 27874251
TI  - Simultaneous analysis of ten low-molecular-mass organic acids in the
      tricarboxylic acid cycle and photorespiration pathway in Thalassiosira pseudonana
      at different growth stages.
AB  - A method using high-performance liquid chromatography coupled with tandem mass
      spectrometry was developed for the simultaneous determination of organic acids in
      microalgae. o-Benzylhydroxylamine was used to derivatize the analytes, and stable
      isotope-labeled compounds were used as internal standards for precise
      quantification. The proposed method was evaluated in terms of linearity,
      recovery, matrix effect, sensitivity, and precision. Linear calibration curves
      with correlation coefficients >0.99 were obtained over the concentration range of
      0.4-40 ng/mL  for glycolic acid, 0.1-10 ng/mL for malic acid and oxaloacetic
      acid, 0.02-2 ng/mL for succinic acid and glyoxylic acid, 4-400 ng/mL for fumaric
      acid, 20-2000 ng/mL for isocitric acid, 2-200 ng mL-1  for citric acid, 100-10000
      ng mL-1  for cis-aconitic acid, and 1-100 ng mL-1  for alpha-ketoglutaric acid.
      Analyte recoveries were between 80.2 and 115.1%, and the matrix effect was
      minimal. Low limits of detection (0.003-1 ng/mL) and limits of quantification
      (0.01-5 ng/mL) were obtained except cis-aconitic acid. Variations in
      reproducibility for standard solution at three different concentrations levels
      were <9%. This is the first report of the simultaneous analysis of ten organic
      acids in microalgae, which promotes better understanding of their growth state
      and provides reference value for high-yield microalgae cultures.

PMID- 27874252
TI  - Pediatric cardiac readmissions: An opportunity for quality improvement?
AB  - OBJECTIVE: Hospital readmissions are increasingly becoming a metric for quality
      in the current landscape of changing and cost effective medicine. However, no 30
      d readmission rates have been established for pediatric cardiac medical patients
      in the United States. Thus, the objective was to determine 30 d readmission rates
      and risk factors associated with readmission for pediatric cardiac patients,
      hypothesizing that pediatric cardiac patients would have significantly higher
      readmission rates than their general pediatric counterparts. DESIGN: This was a
      retrospective cohort study. SETTING: The study took place at a large urban
      academic children's hospital. PATIENTS: The 1124 included patients were
      discharged from the medical cardiology service and had an unplanned readmission
      within 30 d during the period of 2012-2014. MEASURES: Admissions, readmissions,
      diagnoses, demographics, weights, medications, procedures, length of stay, were
      all measured. RESULTS: There were 1993 visits and 408 (20.5%) 30-d readmissions
      in our study. Among the 1124 patients, 219 (19.5%) had at least one 30-d
      readmission. Patient factors associated with increased likelihood of 30-d
      readmission were younger age (median: 197.5 vs 1365.5 d, P < .0001), lower
      discharge weight (6.2 v 14.5 kg, P < .0001) and greater number of diagnoses (P <
      .0001). The encounter factor associated with a 30-d readmission was longer length
      of stay (4 vs 2 d, P < 0.0001). Factors associated with decreased readmissions
      were having had an electrophysiology procedure during their stay, taking an
      angiotensin converting enzyme inhibitor/angiotensin receptor blocker or taking an
      antibiotic. CONCLUSIONS: Readmissions within 30 d among pediatric cardiology
      patients are common. The most common factors associated with readmissions are not
      likely to be modifiable but may serve as important prognostic indicators and as a
      basis for counseling.

PMID- 27874253
TI  - Combined delivery of FGF-2, TGF-beta1, and adipose-derived stem cells from an
      engineered periosteum to a critical-sized mouse femur defect.
AB  - Critical-sized long bone defects suffer from complications including impaired
      healing and non-union due to substandard healing and integration of devitalized
      bone allograft. Removal of the periosteum contributes to the limited healing of
      bone allografts. Restoring a periosteum on bone allografts may provide improved
      allograft healing and integration. This article reports a polysaccharide-based
      tissue engineered periosteum that delivers basic fibroblast growth factor (FGF
      2), transforming growth factor-beta1 (TGF-beta1), and adipose-derived mesenchymal
      stem cells (ASCs) to a critical-sized mouse femur defect. The tissue engineered
      periosteum was evaluated for improving bone allograft healing and incorporation
      by locally delivering FGF-2, TGF-beta1, and supporting ASCs transplantation. ASCs
      were successfully delivered and longitudinally tracked at the defect site for at
      least 7 days post operation with delivered FGF-2 and TGF-beta1 showing a
      mitogenic effect on the ASCs. At 6 weeks post implantation, data showed a non
      significant increase in normalized bone callus volume. However, union ratio
      analysis showed a significant inhibition in allograft incorporation, confirmed by
      histological analysis, due to loosening of the nanofiber coating from the
      allograft surface. Ultimately, this investigation shows our tissue engineered
      periosteum can deliver FGF-2, TGF-beta1, and ASCs to a mouse critical-sized femur
      defect and further optimization may yield improved bone allograft healing. (c)
      2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 900-911, 2017.

PMID- 27874254
TI  - High-throughput ultra high performance liquid chromatography coupled to
      quadrupole time-of-flight mass spectrometry method for the rapid analysis and
      characterization of multiple constituents of Radix Polygalae.
AB  - Radix Polygalae, the dried roots of Polygala tenuifolia and P. sibirica, is one
      of the most well-known traditional Chinese medicinal plants. It is an important
      medicinal plant that has been used as a sedative and to improve memory for a
      number of years in most of Asia. However, the in vivo constituents of the
      multiple constituents from Radix Polygalae remain unknown. In the current study,
      ultra high performance liquid chromatography coupled to quadrupole time-of-flight
      mass spectrometry and the MarkerLynxTM software combined with multiple data
      processing approach were used to study the constituents in vitro and in vivo. A
      rapid and efficient method for the characterization of multiple constituents in
      the herbal medicine Radix Polygalae by ultra high performance liquid
      chromatography coupled to quadrupole time-of-flight mass spectrometry is
      described. In total, 35 compounds in the Radix Polygalae and 13 compounds
      absorbed into blood were characterized. Of the 35 compounds in vitro, ten were
      reported for first time. In the 13 compounds in vivo, six were prototype
      components and seven were metabolites were also elucidated for first time. This
      work narrowed the range of screening the potentially bioactive components and
      provided a basis for the quality control and mechanism of action.

PMID- 27874255
TI  - Multimodal imaging of combined hamartoma of the retina and retinal pigment
      epithelium.

PMID- 27874256
TI  - Correlation of vitamin D levels with tear film stability and secretion in
      patients with dry eye syndrome.
AB  - PURPOSE: To investigate tear film stability and secretion according to serum 25
      hydroxyvitamin D3 [25(OH)D] levels in dry eye patients. METHODS: In this
      retrospective observational study, the medical charts of 92 patients who visited
      the Department of Ophthalmology at Hallym University Kangnam Sacred Heart
      Hospital from April to August 2015 were reviewed. Serum 25(OH)D levels were
      measured. Subjects were divided into three groups according to serum 25(OH)D
      levels: sufficient, inadequate or deficient group. Eye discomfort was measured by
      ocular surface disease index (OSDI). Tear break-up time (TBUT), fluorescein
      staining score and Schirmer's tear secretion test were measured. RESULTS: The
      mean age was 53.38 +/- 13.69 years. Mean serum 25(OH)D level was 14.41 +/- 5.98
      ng/ml. Tear break-up time (TBUT) and tear secretion were positively correlated
      with serum 25(OH)D levels (r = 0.389, p = 0.001; and r = 0.428, p < 0.001,
      Pearson correlation test). Tear break-up time (TBUT) and tear secretion were
      shorter in the vitamin D-deficient group compared to the sufficient group (p =
      0.022 and p = 0.004). Fluorescein staining scores and OSDI scores were not
      different between the three groups. CONCLUSION: Tear break-up time (TBUT) and
      secretion were correlated with serum vitamin D levels. Vitamin D status may be an
      important factor for dry eye syndrome.

PMID- 27874257
TI  - Triazole-Containing Dendrimer-like Core Cross-Linked Micelles that Stabilize Pd
      Nanoparticles as Heterogenized Homogeneous Catalysts for Room-Temperature Suzuki
      Miyaura Reactions in Water.
AB  - Featuring the advantages of both homogeneous (high activity) and heterogeneous
      (recyclability) catalysts, heterogenized homogeneous catalysts (e.g., dendrimer
      stabilized metal nanoparticles) have received much attention in recent years.
      Here, we develop a new triazole-containing dendrimer-like core cross-linked
      micelle (DCCM) stabilized Pd nanoparticles as a highly efficient heterogenized
      homogeneous catalyst for the Suzuki-Miyaura reaction. Both arylboronic acids and
      iodobenzenes with diverse electronic properties performed with excellent
      reactivity under the mild conditions of room temperature, water as the sole
      solvent, and as low as 0.5 % catalyst loading. Importantly, the Pd@triazole-DCCMs
      can tolerate various functional groups well (e.g., alcohol, aldehyde, ester,
      acyl, amino, and cyano, etc.) and give the corresponding biphenyl products in
      high yields. Recycling experiments suggest that the new heterogenized homogeneous
      catalyst can be recovered simply and reused many times with negligible activity
      change.

PMID- 27874258
TI  - Predictive validity of the Braden Scale, Norton Scale, and Waterlow Scale in the
      Czech Republic.
AB  - The aim of this study was to determine the predictive validity of the Braden,
      Norton, and Waterlow scales in 2 long-term care departments in the Czech
      Republic. Assessing the risk for developing pressure ulcers is the first step in
      their prevention. At present, many scales are used in clinical practice, but most
      of them have not been properly validated yet (for example, the Modified Norton
      Scale in the Czech Republic). In the Czech Republic, only the Braden Scale has
      been validated so far. This is a prospective comparative instrument testing
      study. A random sample of 123 patients was recruited. The predictive validity of
      the pressure ulcer risk assessment scales was evaluated based on sensitivity,
      specificity, positive and negative predictive values, and the area under the
      receiver operating characteristic curve. The data were collected from April to
      August 2014. In the present study, the best predictive validity values were
      observed for the Norton Scale, followed by the Braden Scale and the Waterlow
      Scale, in that order. We recommended that the above 3 pressure ulcer risk
      assessment scales continue to be evaluated in the Czech clinical setting.

PMID- 27874259
TI  - Transcatheter closure of calcified patent ductus arteriosus in older adult
      patients: Immediate and 12-month follow-up results.
AB  - OBJECTIVE: To present our experience in transcatheter closure of calcified patent
      ductus arteriosus (PDA) in older adult patients, which has rarely been reported.
      PATIENTS: From 2009 to 2014, a total of 16 patients (median age 58 years) with
      calcified PDA underwent transcatheter closure in our center. All patients were
      symptomatic with major symptoms being exertional dyspnea (in 12), palpitations
      (in 8), and fatigue (in 5). A continuous murmur was heard in all patients. The
      median ductus diameter was 4 mm (range 3-7 mm). The median Qp/Qs was 1.6 (range
      1.4-2.9). INTERVENTIONS: Transcatheter closure was performed for all patients.
      The size of the occluder selected was 2-3 mm greater than the narrowest portion
      of PDA. We experienced difficulties in advancing the multipurpose catheter
      through the calcified duct in about one third of patients (5/16). Considering
      that calcified tissue has a greater tendency to rupture, hence, to close PDA in
      these patients, they adopted the retrograde wire-assisted technique and modified
      the procedure to reduce the shear stress of sheath and avoid any sheath kinking.
      For the remaining 11 patients, the advancement of the multipurpose catheter
      through the calcified duct was smooth and the conventional antegrade approach was
      applied. OUTCOME MEASURES: Clinical examination, standard 12-lead
      electrocardiography, chest x-ray, and transthoracic echocardiography were
      performed before hospital discharge, at 1-, 3-, 6-, and 12-months follow-ups.
      RESULTS: All PDAs were successfully closed. There were no deaths. Three patients
      had a trivial residual shunt, with one also having intravascular hemolysis.
      Following pharmacological treatment, hemolysis signs vanished at 7 days
      postprocedure. The trivial residual shunt disappeared in all three patients at 3
      month follow-up. No new-onset residual shunt, device embolization, device
      dislocation, infective endocarditis, or embolism was observed at all follow-up
      time points. CONCLUSION: Successful closure of calcified PDA with few
      complications in older adult patients was achieved using the duct occluder.

PMID- 27874260
TI  - Phototriggered Secretion of Membrane Compartmentalized Bioactive Agents.
AB  - A strategy for the light-activated release of bioactive compounds (BODIPY,
      colchicine, paclitaxel, and methotrexate) from membrane-enclosed depots is
      described. We have found that membrane-permeable bioagents can be rendered
      membrane impermeable by covalent attachment to cobalamin (Cbl) through a
      photocleavable linker. These Cbl-bioagent conjugates are imprisoned within lipid
      enclosed compartments in the dark, as exemplified by their retention in the
      interior of erythrocytes. Subsequent illumination drives the secretion of the
      bioactive species from red blood cells. Photorelease is triggered by wavelengths
      in the red, far-red, and near-IR regions, which can be pre-assigned by affixing a
      fluorophore with the desired excitation wavelength to the Cbl-bioagent conjugate.
      Pre-assigned wavelengths allow different biologically active compounds to be
      specifically and unambiguously photoreleased from common carriers.

PMID- 27874261
TI  - Outcome of intra-arterial chemotherapy for retinoblastoma and its influencing
      factors: a retrospective study.
AB  - PURPOSE: Intra-arterial chemotherapy (IAC) has become an essential technique for
      the treatment of advanced and relapsed intra-ocular retinoblastoma. The outcome
      of IAC for retinoblastoma is influenced by a variety of medical and non-medical
      factors. In this study, we aimed to examine the outcome of IAC and determine the
      factors influencing clinical outcome. METHODS: A total of 107 eyes of 73 patients
      with retinoblastoma undergoing IAC between January 2011 and April 2013 were
      retrospectively reviewed for clinical outcomes. The factors influencing clinical
      outcomes were determined using univariate and multivariate analyses. RESULTS:
      After IAC, an overall globe salvage rate of 78.5% was observed during follow-up
      periods. Specifically, globe salvage was achieved in Group B (100%), Group C
      (100%), Group D (78.6%), and Group E (62%). Short-term ocular adverse events
      included eyelid oedema (14%), bulbar conjunctiva congestion (29.9%) and excessive
      tearing (9.3%). Long-term complications included vitreous haemorrhage (8.4%),
      subretinal haemorrhage (9.3%), retinal vasculopathy (7.5%) and ophthalmic artery
      spasm with reperfusion (4.7%). Univariate and multivariate analyses showed that
      the globe salvage of IAC was significantly associated with tumour staging and
      previous treatment (p < 0.05, respectively). CONCLUSION: Intra-arterial
      chemotherapy (IAC) is safe and effective for the management of retinoblastoma.
      Patients with advanced retinoblastoma and previous failed treatment may have a
      poor outcome after IAC.

PMID- 27874262
TI  - A Deep Hydrophobic Binding Cavity is the Main Interaction for Different Y2 R
      Antagonists.
AB  - The neuropeptide Y2 receptor (Y2 R) is involved in various pathophysiological
      processes such as epilepsy, mood disorders, angiogenesis, and tumor growth.
      Therefore, the Y2 R is an interesting target for drug development. A detailed
      understanding of the binding pocket could facilitate the development of highly
      selective antagonists to study the role of Y2 R in vitro and in vivo. In this
      study, several residues crucial to the interaction of BIIE0246 and SF-11
      derivatives with Y2 R were investigated by signal transduction assays. Using the
      experimental results as constraints, the antagonists were docked into a
      comparative structural model of the Y2 R. Despite differences in size and
      structure, all three antagonists display a similar binding site, including a deep
      hydrophobic cavity formed by transmembrane helices (TM) 4, 5, and 6, as well as a
      hydrophobic patch at the top of TM2 and 7. Additionally, we suggest that the
      antagonists block Q3.32 , a position that has been shown to be crucial for
      binding of the amidated C terminus of NPY and thus for receptor activation.

PMID- 27874263
TI  - Ensemble perception of color in autistic adults.
AB  - Dominant accounts of visual processing in autism posit that autistic individuals
      have an enhanced access to details of scenes [e.g., weak central coherence] which
      is reflected in a general bias toward local processing. Furthermore, the
      attenuated priors account of autism predicts that the updating and use of summary
      representations is reduced in autism. Ensemble perception describes the
      extraction of global summary statistics of a visual feature from a heterogeneous
      set (e.g., of faces, sizes, colors), often in the absence of local item
      representation. The present study investigated ensemble perception in autistic
      adults using a rapidly presented (500 msec) ensemble of four, eight, or sixteen
      elements representing four different colors. We predicted that autistic
      individuals would be less accurate when averaging the ensembles, but more
      accurate in recognizing individual ensemble colors. The results were consistent
      with the predictions. Averaging was impaired in autism, but only when ensembles
      contained four elements. Ensembles of eight or sixteen elements were averaged
      equally accurately across groups. The autistic group also showed a corresponding
      advantage in rejecting colors that were not originally seen in the ensemble. The
      results demonstrate the local processing bias in autism, but also suggest that
      the global perceptual averaging mechanism may be compromised under some
      conditions. The theoretical implications of the findings and future avenues for
      research on summary statistics in autism are discussed. Autism Res 2017, 10: 839
      851. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27874265
TI  - Incidental brain MRI findings in an autism twin study.
AB  - Brain magnetic resonance imaging (MRI) studies suggest the prevalence of
      asymptomatic "incidental" findings (IF) in autism spectrum disorder (ASD) is
      similar to that of neurotypically developing (NT) controls. However, given the
      causes of IF may include both genetic and environmental factors, a twin study
      would facilitate comparing brain IF between ASD and NT subjects. MRI scans were
      examined to assess the prevalence of brain IF in twin "case pairs" (at least one
      twin with diagnosis of ASD) and twin "control pairs" (NT). Fifty case pairs and
      thirty-two control pairs were analyzed. IF were found in 68% of subjects with
      ASD, 71% of unaffected ASD siblings, and in 58% of control subjects (P = 0.4). IF
      requiring clinical follow-up occurred more frequently in subjects with ASD
      compared to NT controls (17% vs. 5%, respectively; P = 0.02). The concordance
      rate of IF in twins was 83%. A mixed effects model found younger age, male sex,
      and "family environment" to be significantly associated with IF. There was no
      difference in the prevalence rate of IF between ASD subjects and NT controls.
      More IF required clinical follow-up in ASD subjects compared to NT controls. The
      prevalence rate of IF observed in this twin study was higher than rates
      previously reported in singleton studies. Our results suggest the shared
      environment of twins - perhaps in utero - increases the risk of brain IF. Brain
      MRI in the initial work-up of ASD may be indicated in twins, especially in males.
      Autism Res 2017, 10: 113-120. (c) 2016 International Society for Autism Research,
      Wiley Periodicals, Inc.

PMID- 27874264
TI  - Photobiomodulation in human muscle tissue: an advantage in sports performance?
AB  - Photobiomodulation (PBM) describes the use of red or near-infrared (NIR) light to
      stimulate, heal, and regenerate damaged tissue. Both preconditioning (light
      delivered to muscles before exercise) and PBM applied after exercise can increase
      sports performance in athletes. This review covers the effects of PBM on human
      muscle tissue in clinical trials in volunteers related to sports performance and
      in athletes. The parameters used were categorized into those with positive
      effects or no effects on muscle performance and recovery. Randomized controlled
      trials and case-control studies in both healthy trained and untrained
      participants, and elite athletes were retrieved from MEDLINE up to 2016.
      Performance metrics included fatigue, number of repetitions, torque, hypertrophy;
      measures of muscle damage and recovery such as creatine kinase and delayed onset
      muscle soreness. Searches retrieved 533 studies, of which 46 were included in the
      review (n = 1045 participants). Studies used single laser probes, cluster of
      laser diodes, LED clusters, mixed clusters (lasers and LEDs), and flexible LED
      arrays. Both red, NIR, and red/NIR mixtures were used. PBM can increase muscle
      mass gained after training, and decrease inflammation and oxidative stress in
      muscle biopsies. We raise the question of whether PBM should be permitted in
      athletic competition by international regulatory authorities.

PMID- 27874266
TI  - Meta-analysis of neuropsychological measures of executive functioning in children
      and adolescents with high-functioning autism spectrum disorder.
AB  - Existing literature on the profile of executive dysfunction in autism spectrum
      disorder showed inconsistent results. Age, comorbid attention
      deficit/hyperactivity disorder (ADHD) and cognitive abilities appeared to play a
      role in confounding the picture. Previous meta-analyses have focused on a few
      components of executive functions. This meta-analysis attempted to delineate the
      profile of deficit in several components of executive functioning in children and
      adolescents with high-functioning autism spectrum disorder (HFASD). Ninety-eight
      English published case-control studies comparing children and adolescents with
      HFASD with typically developing controls using well-known neuropsychological
      measures to assess executive functions were included. Results showed that
      children and adolescents with HFASD were moderately impaired in verbal working
      memory (g = 0.67), spatial working memory (g = 0.58), flexibility (g = 0.59),
      planning (g = 0.62), and generativity (g = 0.60) except for inhibition (g =
      0.41). Subgroup analysis showed that impairments were still significant for
      flexibility (g = 0.57-0.61), generativity (g = 0.52-0.68), and working memory (g
      = 0.49-0.56) in a sample of autism spectrum disorder (ASD) subjects without
      comorbid ADHD or when the cognitive abilities of the ASD group and the control
      group were comparable. This meta-analysis confirmed the presence of executive
      dysfunction in children and adolescents with HFASD. These deficits are not solely
      accounted for by the effect of comorbid ADHD and the general cognitive abilities.
      Our results support the executive dysfunction hypothesis and contribute to the
      clinical understanding and possible development of interventions to alleviate
      these deficits in children and adolescents with HFASD. Autism Res 2017, 10: 911
      939. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27874267
TI  - Human Digital Meissner Corpuscles Display Immunoreactivity for the
      Multifunctional Ion Channels Trpc6 and Trpv4.
AB  - Ion channels are at the basis of the sensory processes including mechanosensing.
      Some members of the transient receptor potential (TRP) ion channel superfamily
      have been proposed as mechanosensors, but their putative role in
      mechanotransduction is controversial. Among them there are TRP canonical 6
      (TRPC6) and TRP vanilloid 4 (TRPV4) ion channels, which are known to cooperate in
      mechanical hyperalgesia. Here, we investigated the occurrence, distribution, and
      possible colocalization of TRPC6 and TRPV4 in human digital Meissner sensory
      corpuscles using immunohistochemistry and double immunofluorescence (associate
      with markers for specific corpuscular constituents). TRPC6 immunoreactivity was
      restricted to the axon of Meissner corpuscles, whereas TRPV4 was detected in the
      axon but also in the lamellar cells. Moreover, axonal colocalization of TRPV4 and
      TRPC6 was found in the digital Meissner corpuscles. Present results demonstrate
      for the first time the occurrence and colocalization of two ion channels
      candidates to mechanosensors in human cutaneous mechanoreceptors. The functional
      significance of these ion channels in that place remains to be clarified, but
      should be related to different properties of mechanosensitivity. Anat Rec,
      300:1022-1031, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27874269
TI  - Highly Active NaTaO3 -Based Photocatalysts for CO2 Reduction to Form CO Using
      Water as the Electron Donor.
AB  - Doped NaTaO3 (NaTaO3 :A, where A=Mg, Ca, Sr, Ba, or La) has arisen as a highly
      active photocatalyst for CO2 reduction to simultaneously form CO, H2 , and O2
      using water as the electron donor when used with an Ag cocatalyst, under UV
      irradiation, and with 1 atm (0.1 MPa) of CO2 . The ratio of the number of reacted
      electrons/holes was almost unity, indicating that water was consumed as the
      electron donor. A liquid-phase reduction method for loading of the Ag cocatalyst
      was superior to photodeposition and impregnation methods. The Ag cocatalyst
      loaded NaTaO3 :Ba was the most active photocatalyst in water with no required
      additives. The addition of bases, such as hydrogencarbonate, was effective to
      enhance the CO formation for Mg-, Ca-, Sr-, Ba-, and La-doped NaTaO3
      photocatalysts with an Ag cocatalyst. Ca- and Sr-doped NaTaO3 photocatalysts
      showed especially high activity along with the Ba-doped photocatalyst in the
      aqueous NaHCO3 solution. The selectivity for the CO formation [CO/(CO+H2 )] on Ca
      , Sr-, and Ba-doped NaTaO3 photocatalysts with Ag cocatalyst reached around 90 %.

PMID- 27874268
TI  - A combination of resveratrol and quercetin induces browning in white adipose
      tissue of rats fed an obesogenic diet.
AB  - OBJECTIVE: To analyze whether a combination of quercetin (Q) and resveratrol
      (RSV) would induce a white adipose tissue (WAT) browning effect. METHODS: Thirty
      six rats were fed an obesogenic diet and divided into four groups: control,
      treated with RSV (15 mg/kg body weight/day; RSV group), treated with Q (30 mg/kg
      body weight/day; Q group), or treated with both polyphenols (RSV + Q group).
      RESULTS: After 6 weeks, body and WAT weights were significantly reduced in the
      RSV + Q group. In perirenal WAT of the control, RSV, and Q groups, white
      unilocular adipocytes appeared in the majority of cells, while in the RSV + Q
      group numerous multilocular adipocytes with positive immunostaining for UCP1 were
      observed. The presence of UCP1 was confirmed by Western blot. This group also
      revealed increased mRNA levels of Cidea, Hocx9, Bmp4, Slc27a1, Pat2, Atgl, and
      Atp5d. Interscapular brown adipose tissue weight showed no differences between
      groups, but the Cidea mRNA level was increased in the RSV group, the Cox-2 mRNA
      level in the RSV + Q group, and UCP1 protein expression in the RSV and the RSV +
      Q groups. CONCLUSIONS: This study demonstrated that the RSV + Q combination
      produces a brown-like remodeling effect in perirenal WAT, as well as increased
      UCP1 protein expression in interscapular brown adipose tissue.

PMID- 27874270
TI  - Neurodevelopmental disorders are highly over-represented in children with
      obesity: A cross-sectional study.
AB  - OBJECTIVE: To investigate prevalence of neurodevelopmental disorders in children
      with obesity and to compare body mass index (BMI) and metabolic profile in the
      children. METHODS: Seventy-six children (37 girls, 39 boys) were consecutively
      recruited from a university outpatient clinic specialized in severe obesity.
      Neurodevelopmental disorders including attention-deficit/hyperactivity disorder
      (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder
      (DCD) were assessed using interviews and questionnaires. Neurodevelopmental
      diagnoses were collected retrospectively in medical records. RESULTS: BMI ranged
      between 1.9 and 5.9 SDS and age between 5.1 and 16.5 years. In 13.2% and 18.4%
      ASD and ADHD was assigned, respectively. In addition, 25% screened positive for
      DCD, 31.6% had at least one neurodevelopmental disorder, and 18.4% had a parent
      who screened positive for adult ADHD. Girls with ASD/ADHD had higher BMI SDS than
      girls without neurodevelopmental disorder (P = 0.006). CONCLUSIONS: One third of
      children with obesity referred to specialist centers have a neurodevelopmental
      disorder including deviant motor skills, and these problems may deteriorate
      weight status. One fifth of the parents exhibit ADHD symptomatology which could
      partly explain the poor adherence by some families in obesity units. Future
      obesity therapy could benefit from incorporating a neurodevelopmental treatment
      approach.

PMID- 27874271
TI  - Diagnostic model generated by MRI-derived brain features in toddlers with autism
      spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder mainly
      showed atypical social interaction, communication, and restricted, repetitive
      patterns of behavior, interests and activities. Now clinic diagnosis of ASD is
      mostly based on psychological evaluation, clinical observation and medical
      history. All these behavioral indexes could not avoid defects such as
      subjectivity and reporter-dependency. Therefore researchers devoted themselves to
      seek relatively stable biomarkers of ASD as supplementary diagnostic evidence.
      The goal of present study is to generate relatively stable predictive model based
      on anatomical brain features by using machine learning technique. Forty-six ASD
      children and thirty-nine development delay children aged from 18 to 37 months
      were evolved in. As a result, the predictive model generated by regional average
      cortical thickness of regions with top 20 highest importance of random forest
      classifier showed best diagnostic performance. And random forest was proved to be
      the optimal approach for neuroimaging data mining in small size set and thickness
      based classification outperformed volume-based classification and surface area
      based classification in ASD. The brain regions selected by the models might
      attract attention and the idea of considering biomarkers as a supplementary
      evidence of ASD diagnosis worth exploring. Autism Res 2017, 0: 000-000. (c) 2016
      International Society for Autism Research, Wiley Periodicals, Inc. Autism Res
      2017, 10: 620-630. (c) 2016 International Society for Autism Research, Wiley
      Periodicals, Inc.

PMID- 27874272
TI  - Catalytic Transesterification of Starch with Plant Oils: A Sustainable and
      Efficient Route to Fatty Acid Starch Esters.
AB  - The transesterification of maize starch with olive oil or high oleic sunflower
      oil was studied under homogeneous conditions in the presence of 1,5,7
      triazabicyclo[4.4.0]dec-5-ene (TBD) as catalyst. Most importantly, this method
      used two renewable resources directly, without any pretreatment or
      derivatization, for the synthesis of polymeric materials with desirable
      properties. Moreover, the solvent, oils, and catalyst could be recovered through
      facile work-up and reused for further modifications. The obtained fatty acid
      starch esters (FASEs) were highly soluble in common organic solvents and were
      thoroughly characterized. Degrees of substitution (DS) were calculated using 31 P
      NMR spectroscopy, and DS values of approximately 1.3 were obtained. Differential
      scanning calorimetry analysis revealed thermal transitions of the modified
      starches at approximately 80-90  degrees C. Films were produced from these FASEs,
      and their hydrophobic surfaces were characterized using contact-angle
      measurements. Furthermore, mechanical properties were examined using tensile
      strength measurements and showed approximately 40 and 80 % elongation at break
      for modified maize starch and modified amylose from maize, respectively.

PMID- 27874273
TI  - Association testing of vasopressin receptor 1a microsatellite polymorphisms in
      non-clinical autism spectrum phenotypes.
AB  - Variation in the AVPR1a gene, which codes for a receptor for the neurohormone
      vasopressin, has been found to relate to autism risk. Interestingly, variation in
      this gene also relates to differences in social behaviour in non-clinical
      populations. Variation in this gene may affect expression of AVPR1a receptors in
      brain areas involved in social behaviour. Here, we tested whether AVPR1a
      variation was associated with Autism Quotient (AQ) scores, a questionnaire that
      measures non-clinical manifestations of autism, in a population of 873 healthy
      university students. The AVPR1a RS1 and RS3 microsatellites were examined, and
      variants were categorized as "long" or "short". The RS3 long/long genotype was
      significantly associated with a higher AQ score (i.e., a more autistic-like
      phenotype) for the combined population and for females only. Further examination
      showed that this relationship was due to a specific RS3 variant, termed the
      "target allele", which previous research has linked to reduced altruism and
      increased marital problems in healthy individuals. We also observed that the
      relationship between RS3 genotype and AQ score was mainly due to the "attention
      switching" (the ability to shift attention from one task to another) component of
      the questionnaire; this ability is commonly impaired in autism spectrum
      disorders. Overall, our study establishes continuity between the existing AVPR1a
      research in clinical and non-clinical populations. Our results suggest that
      vasopressin may exert its effects on social behaviour in part by modulating
      attentional focus between social and non-social cues. Autism Res 2017, 10: 750
      756. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27874274
TI  - Differential association between sarcopenia and metabolic phenotype in Korean
      young and older adults with and without obesity.
AB  - OBJECTIVE: To determine whether sarcopenia was associated with metabolic
      phenotype in subjects with and without obesity. METHODS: A total of 6,021
      participants (2,592 men, 3,429 women) aged 30 to 93 years were assessed using
      data from the 2009 Korea National Health and Nutrition Examination Survey.
      Sarcopenia was defined as appendicular skeletal muscle mass divided by weight (%)
      that is <1 SD below the sex-specific mean for young adults. Metabolically
      unhealthy was defined as >=2 components of metabolic syndrome or the presence of
      hypertension, diabetes, or cardiovascular disease. Obesity was defined as body
      mass index >=25.0 kg/m2 . RESULTS: Sarcopenia was associated with a metabolically
      unhealthy phenotype in nonobese men independent of age, smoking, regular physical
      activity, daily energy intake, total body fat, fasting insulin, non-HDL
      cholesterol, white blood cell count, ferritin level, and 25(OH) vitamin D level
      (OR per 1 SD increment (95% CI) 1.88 (1.28-2.75), P < 0.01), but this association
      was confounded by and not independent of total body fat in nonobese women.
      Sarcopenia was not associated with a metabolically unhealthy phenotype in
      subjects with obesity. CONCLUSIONS: Sarcopenia was independently associated with
      a metabolically unhealthy phenotype in nonobese men, but this association was not
      evident in nonobese women or subjects with obesity.

PMID- 27874275
TI  - Executive functioning in men and women with an autism spectrum disorder.
AB  - Executive functioning (EF) is thought to be linked to autism spectrum disorders
      (ASD) specific symptoms. The majority of research has focused on children and
      adolescents with ASD and, therefore, little is known about EF in adults.
      Furthermore, little is known about gender differences. Ninety-nine men and forty
      women with ASD were compared with and 35 neurotypical men 25 neurotypical women.
      Participants were matched on age, total intelligence, and verbal ability. The
      following instruments were used to measure executive functioning: digit span and
      letter and number sequencing of the WAIS-III, Tower of Hanoi, WCST, and Verbal
      fluency. Multiple analysis of variance was conducted to determine group
      differences. Women with ASD performed worse on the working memory tasks of the
      WAIS-III than neurotypical women. Furthermore, women with ASD had more
      perseverations on the WCST than neurotypical women. The gender comparison in the
      ASD group showed differences in performance on mental flexibility (WCST), working
      memory (WAIS-III), generativity and self-monitoring (Verbal fluency). However,
      these differences were unequivocal and no gender specific cognitive profile could
      be pinpointed. Individual strengths and frailties should be highlighted in
      clinical practice, as impairments in EF can be under influence of the overall
      cognitive abilities of the individual. Furthermore, gender differences were
      found. This could explain differences in representation of ASD symptoms in both
      groups. These differences show how important thorough diagnostics are. Autism Res
      2017, 10: 940-948. (c) 2016 International Society for Autism Research, Wiley
      Periodicals, Inc.

PMID- 27874276
TI  - Prenatal toxoplasmosis antibody and childhood autism.
AB  - There is evidence that some maternal infections during the prenatal period are
      associated with neurodevelopmental disorders, such as childhood autism. However,
      the association between autism and Toxoplasma gondii (T. gondii), an
      intracellular parasite, remains unclear. The authors examined whether
      serologically confirmed maternal antibodies to T. gondii are associated with odds
      of childhood autism in offspring. The study is based on a nested case-control
      design of a large national birth cohort (N = 1.2 million) and the national
      psychiatric registries in Finland. There were 874 cases of childhood autism and
      controls matched 1:1 on date of birth, sex, birthplace and residence in Finland.
      Maternal sera were prospectively assayed from a national biobank for T. gondii
      IgM and IgG antibodies; IgG avidity analyses were also performed. High maternal
      T. gondii IgM antibody was associated with a significantly decreased odds of
      childhood autism. Low maternal T. gondii IgG antibody was associated with
      increased offspring odds of autism. In women with high T. gondii IgM antibodies,
      the IgG avidity was high for both cases and controls, with the exception of three
      controls. The findings suggest that the relationship between maternal T. gondii
      antibodies and odds of childhood autism may be related to the immune response to
      this pathogen or the overall activation of the immune system. Autism Res 2017,
      10: 769-777. (c) 2016 International Society for Autism Research, Wiley
      Periodicals, Inc.

PMID- 27874277
TI  - Graphite//LiNi0.5 Mn1.5 O4 Cells Based on Environmentally Friendly Made-in-Water
      Electrodes.
AB  - The performance of graphite//LiNi0.5 Mn1.5 O4 (LNMO) cells, both electrodes of
      which are made using water-soluble sodium carboxymethyl cellulose (CMC) binder,
      is reported for the first time. The full cell performed outstandingly over 400
      cycles in the conventional electrolyte ethylene carbonate/dimethyl carbonate-1 m
      LiPF6 , and the delivered specific energy at the 100th, 200th, 300th, and 400th
      cycle corresponded to 82, 78, 73, and 66 %, respectively, of the initial energy
      value of 259 Wh kg-1 (referring to the sum of the two electrode-composite
      weights). The good stability of high-voltage, LNMO-CMC-based electrodes upon long
      term cycling is discussed and the results are compared to those of LNMO-composite
      electrodes with polyvinylidene fluoride (PVdF). LNMO-CMC electrodes outperformed
      those with PVdF binder, displaying a capacity retention of 83 % compared to 62 %
      for the PVdF-based electrodes after 400 cycles at 1 C. CMC promotes a more
      compact and stable electrode surface than PVdF; undesired interfacial reactions
      at high operating voltages are mitigated, and the thickness of the passivation
      layer on the LNMO surface is reduced, thereby enhancing its cycling stability.

PMID- 27874279
TI  - Cucurmin, anticancer, & antitumor perspectives: A comprehensive review.
AB  - Cucurmin, a naturally yellow component isolated from turmeric, ability to prevent
      various life-style related disorders. The current review article mainly
      emphasizes on different anticancer perspectives of cucurmin, i.e., colon,
      cervical, uterine, ovarian, prostate head and neck, breast, pulmonary, stomach
      and gastric, pancreatic, bladder oral, oesophageal, and bone cancer. It holds a
      mixture of strong bioactive molecule known as cucurminoids that has ability to
      reduce cancer/tumor at initial, promotion and progression stages of tumor
      development. In particular, these compounds block several enzymes required for
      the growth of tumors and may therefore involve in tumor treatments. Moreover, it
      modulates an array of cellular progressions, i.e., nitric oxide synthetase
      activity, protein kinase C activity, epidermal growth factor (EGF) receptor
      intrinsic kinase activity, nuclear factor kappa (NF-kB) activity, inhibiting
      lipid peroxidation and production of reactive oxygen species. However, current
      manuscript summarizes most of the recent investigations of cucurmin but still
      further research should be conducted to explore the role of curcumin to mitigate
      various cancers.

PMID- 27874281
TI  - The therapeutic potential of plant flavonoids on rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an autoimmune condition that mainly affects
      peripheral joints. Although immunosuppressive drugs and non-steroidal anti
      inflammatory drugs (NSAIDs) are used to treat this condition, these drugs have
      severe side effects. Flavonoids are the most abundant phenolic compounds which
      exhibit anti-oxidant, anti-inflammatory and immunomodulatory properties. Many
      bioactive flavonoids have powerful anti-inflammatory effects. However, a very few
      have reached clinical use. Dietary flavonoids have been reported to control joint
      inflammation and alleviate arthritis symptoms in both human RA and animal models
      of arthritis. There is little scientific evidence about their mechanism of
      actions in RA. We review the therapeutic effects of different groups of
      flavonoids belonging to the most common and abundant groups on RA. In particular,
      the probable mechanisms of major flavonoids on cells and chemical messengers
      involved in the inflammatory signaling components of RA are discussed in detail.

PMID- 27874278
TI  - Placental growth factor and its potential role in diabetic retinopathy and other
      ocular neovascular diseases.
AB  - The role of vascular endothelial growth factor (VEGF), including in retinal
      vascular diseases, has been well studied, and pharmacological blockade of VEGF is
      the gold standard of treatment for neovascular age-related macular degeneration,
      retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF,
      previously known as PlGF), a homologue of VEGF, is a multifunctional peptide
      associated with angiogenesis-dependent pathologies in the eye and non-ocular
      conditions. Animal studies using genetic modification and pharmacological
      treatment have demonstrated a mechanistic role for PGF in pathological
      angiogenesis. Inhibition decreases neovascularization and microvascular
      abnormalities across different models, including oxygen-induced retinopathy,
      laser-induced choroidal neovascularization and in diabetic mice exhibiting
      retinopathies. High levels of PGF have been found in the vitreous of patients
      with diabetic retinopathy. Despite these strong animal data, the exact role of
      PGF in pathological angiogenesis in retinal vascular diseases remains to be
      defined, and the benefits of PGF-specific inhibition in humans with retinal
      neovascular diseases and macular oedema remain controversial. Comparative
      effectiveness research studies in patients with diabetic retinal disease have
      shown that treatment that inhibits both VEGF and PGF may provide superior
      outcomes in certain patients compared with treatment that inhibits only VEGF.
      This review summarizes current knowledge of PGF, including its relationship to
      VEGF and its role in pathological angiogenesis in retinal diseases, and
      identifies some key unanswered questions about PGF that can serve as a pathway
      for future basic, translational and clinical research.

PMID- 27874280
TI  - A survey of the mechanisms of action of anticancer transition metal complexes.
AB  - Metal complexes have been the subject of numerous investigations in oncology but,
      despite the plethora of newly synthesized compounds, their precise mechanisms of
      action remain generally unknown or, for the best, incompletely determined. The
      continuous development of efficient and sensitive techniques in analytical
      chemistry and molecular biology gives scientists new tools to gather information
      on how metal complexes can be effective toward cancer. This review focuses on
      recent findings about the anticancer mechanism of action of metal complexes and
      how the ligands can be used to tune their pharmacological and physicochemical
      properties.

PMID- 27874282
TI  - Treatment management between orthodontists and general practitioners performing
      clear aligner therapy.
AB  - OBJECTIVE: To investigate differences in case selection, treatment management,
      and aligner treatment expertise between orthodontists and general practitioners.
      MATERIALS AND METHODS: A parallel pair of original surveys with three sections
      (case selection, treatment management, and demographics) was sent to
      orthodontists (N = 1000) and general dentists (N = 1000) who were providers of
      aligner treatment. RESULTS: Orthodontists had treated significantly more patients
      with aligners, had treated more patients with aligners in the previous 12 months,
      and had received more aligner training than general dentists (P < .0001). In
      general, case confidence increased with increasing experience for both
      orthodontists and general dentists. After adjusting for experience, there was a
      significant difference in aligner case confidence between orthodontists and
      general dentists for several malocclusions. General dentists were more confident
      than orthodontists in treating deep bite, severe crowding, and Class II
      malocclusions with aligners (P <= .0001). Significant differences were also found
      for all treatment management techniques except interproximal reduction.
      CONCLUSION: There was a significant difference in case selection, treatment
      management, and aligner expertise between orthodontists and general dentists,
      although the differences in case selection were small. Overall, it was shown that
      orthodontists and general dentists elected to treat a variety of moderate to
      severe malocclusions with aligners but with different utilization of recommended
      auxiliaries, perhaps demonstrating a difference in treatment goals.

PMID- 27874283
TI  - The effect of root and bone visualization on perceptions of the quality of
      orthodontic treatment simulations.
AB  - OBJECTIVE: To evaluate the effect of root and bone visibility on orthodontists'
      perceptions of the quality of treatment simulations. MATERIAL AND METHODS: An
      online survey was used to present orthodontists with setups generated for 10
      patients in two different types of view: with and without bone and roots as
      modeled from a cone-beam computed tomography (CBCT) scan. The orthodontists were
      asked to rate the quality of the setups from poor to ideal on a 100-point visual
      analog scale and, if applicable, to identify features of concern that led them to
      giving a setup a less-than-ideal rating. RESULTS: The quality ratings were
      significantly lower when roots and bone were visible in the setups (P < .0001).
      Buccolingual inclination and periodontal concerns were selected significantly
      more often as reasons for a less-than-ideal rating when roots and bone were
      shown, whereas occlusal relationship, overjet, occlusal contacts, and arch form
      were selected significantly more often as reasons for a less-than-ideal rating
      when roots and bone were not shown. The odds of selecting periodontal concerns as
      a reason for a less-than-ideal setup rating were 331 times greater when roots and
      bones were visible than when they were not. CONCLUSIONS: Additional diagnostic
      information derived from CBCT scans affects orthodontists' perceptions of the
      overall case quality, which may influence their treatment-planning decisions.

PMID- 27874285
TI  - Modern tools for the chemical ligation and synthesis of modified peptides and
      proteins.
AB  - The ability to improve nature's capacity by introducing modification of
      biological interest in proteins and peptides (P&P) is one of the modern
      challenges in synthetic chemistry. Due to the unfavorable pharmacokinetic
      properties, many native P&P are of little use as therapeutic agents. Today, few
      methods for the preparation of modified proteins are available. Initially
      introduced to realize the ligation between two standard peptidic sequences, and
      hence to afford native proteins, the modern chemical methodologies, in other
      words native chemical ligation, expressed ligation, Staudinger ligation,
      auxiliary mediated ligation, aldehyde capture, etc., can be virtually utilized to
      ligate a variety of peptidomimetic partners, allowing a systematic access to
      modified, unnatural large P&P.

PMID- 27874284
TI  - Effects of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs) on
      glioblastoma cells (U87).
AB  - The impact of extremely low-frequency pulsed electromagnetic fields (ELF-PEMFs)
      at various frequencies and amplitudes was investigated on cell cycle, apoptosis
      and viability of the Glioblastoma Multiforme (GBM) cell line (U87), in vitro. The
      GBM is a malignant brain tumor with high mortality in humans and poorly
      responsive to the most common type of cancer treatments, such as surgery,
      chemotherapy and radiation therapy. U87 cells with five experimental groups (I-V)
      were exposed to various ELF-PEMFs for 2, 4 and 24 h, as follows: (I) no exposure,
      control; (II) 50 Hz 100 +/- 15 G; (III) 100 Hz 100 +/- 15 G; (IV) 10 Hz 50 +/- 10
      G; (V) 50 Hz 50 +/- 10 G. The morphology properties, cell viability and gene
      expression of proteins involved in cell cycle regulation (Cyclin-D1 and P53) and
      apoptosis (Caspase-3) were investigated. After 24 h, the cell viability and
      Cyclin-D1 expression increased in Group II (30%, 45%), whereas they decreased in
      Groups III (29%, 31%) and IV (21%, 34%); P53 and Caspase-3 elevated only in Group
      III; and no significant difference was observed in Group V, respectively,
      compared with the control (p < 0.05). The data suggest that the proliferation and
      apoptosis of human GBM are influenced by exposure to ELF-PEMFs in different time
      dependent frequencies and amplitudes. The fact that some of the ELF-PEMFs
      frequencies and amplitudes favor U87 cells proliferation indicates precaution for
      the use of medical devices related to the MFs on cancer patients. On the other
      hand, some other ELF-PEMFs frequencies and intensities arresting U87 cells growth
      could open the way to develop novel therapeutic approaches.

PMID- 27874286
TI  - Identification of bile survivin and carbohydrate antigen 199 in distinguishing
      cholangiocarcinoma from benign obstructive jaundice.
AB  - AIM: To investigate whether bile survivin and carbohydrate antigen 199 (CA199)
      can be helpful in distinguishing cholangiocarcinoma (malignant obstructive
      jaundice) from benign obstructive jaundice. METHODS: Receiver operating
      characteristic curve was used to evaluate the feasibility of bile survivin and
      CA199 in differentiating cholangiocarcinoma from benign obstructive jaundice.
      RESULTS: The area under the curve for survivin and CA199 in bile and serum were
      0.780 (p < 0.001), 0.6 (p = 0.084), 0.746 (p < 0.001) and 0.542 (p = 0.464),
      respectively. Combination of bile survivin and CA199 could improve the diagnostic
      capability. CONCLUSION: Bile survivin and CA199 are significantly increased in
      patients with cholangiocarcinoma and may be useful biomarkers in differentiating
      distinguishing cholangiocarcinoma from benign obstructive jaundice.

PMID- 27874287
TI  - Impact of Saccharomyces cerevisiae metabolites produced during fermentation on
      bread quality parameters: A review.
AB  - Although bread making with the use of Baker's yeast has a long tradition in human
      history, little attention has been paid to the connection between yeast addition
      and the final bread quality. Nowadays, bakers mainly use different flour
      additives such as enzymes (amylases, hemicellulases, and proteases) to change and
      improve dough properties and/or bread quality. Another strategy is the use of
      modified industrial Baker's yeast. To date, there is no yeast strain used in the
      baking industry, which is genetically modified, despite some studies
      demonstrating that the application of recombinant DNA technology is a possibility
      for improved strains suitable for baking. However, due to the fact that the
      majority of consumers in Europe highly reject the use of genetically modified
      microorganisms in the production of food, other strategies to improve bread
      quality must be investigated. Such a strategy would be a reconsideration of the
      selection of yeast strains used for the baking process. Next to the common
      criteria, the requirement for adequate gas production, more attention should be
      paid on how yeast impacts flavor, shelf life, color, and the nutritional value of
      baked products, in a similar way to which yeast strains are selected in the wine
      and brewing industries.

PMID- 27874288
TI  - N-heterocyclic carbene complexes of silver and gold as novel tools against breast
      cancer progression.
AB  - AIM: Metal carbenic complexes have received considerable attention in both the
      catalysis and biological fields for their potential applications in cancer and
      antimicrobial therapies. RESULTS: A small series of new silver and gold N
      heterocyclic carbene complexes has been designed and synthesized. Among the
      tested complexes, one compound was particularly active in inhibiting anchorage
      dependent and -independent breast cancer proliferation, and inducing cell
      apoptosis via a mitochondria-related process. The antitumor activity was
      associated to the transcriptional activation of the tumor suppressor gene p53 in
      an Sp1-dependent manner, as evidenced by biological and docking studies.
      CONCLUSION: Our results highlight the importance and the versatility of N
      heterocyclic carbene complexes of gold and silver as useful tools against breast
      cancer progression.

PMID- 27874289
TI  - Epigenetic changes as prognostic predictors in endometrial carcinomas.
AB  - Endometrial carcinoma is one of the most frequent gynecological malignancies of
      the female. The diagnostic and prognostic markers for the high-risk subgroups
      with unfavorable prognosis are under intense debate worldwide, and, therefore,
      the aim of this study was to identify new potential DNA methylation markers for
      the high-risk groups. We used the Illumina Infinium HumanMethylation450 BeadChip
      to analyze the DNA methylation pattern and investigated its association with
      clinicopathological features important for defining the high-risk (FIGO-grade 3)
      and low-risk (FIGO-grade 1) groups of patients with endometrial cancer (n = 31
      and n = 39, respectively). We identified specific DNA methylation signature in
      high-risk endometrial tumors, and potential molecular biomarker genes (TBX2,
      CHST11, and NID2) associated with unfavorable clinical predictive and prognostic
      factors.

PMID- 27874290
TI  - Impact of clinical factors on outcome of leukemia patients with TLS-ERG fusion
      gene.
AB  - We report the clinical features and outcome of 22 TLS-ERG+ leukemia patients (20
      AML and 2 B-ALL). TLS-ERG was tightly associated with extramedullary disease
      (EMD), complex chromosome abnormalities, and high risk gene mutations including
      IKZF1, WT1, TET2, NOTCH2, and PHF6. The 6-month leukemia free survival (LFS) with
      and without EMD was 75% and 83.3% (p = .017). 11/20 AML patients received
      allogeneic hematopoietic stem cell transplantation (HCT). The 1-year overall
      survival (OS) in non-HCT and HCT group was 62.5% and 90% (p = .026), but the 6
      month LFS in non-HCT and HCT group was 55.6% and 100% (p = .192). The 6-month LFS
      of patients with complete remission (CR) before HCT versus those with no response
      (NR) was 67.5% and 0, respectively (p = .034). In conclusion, the leukemia burden
      before HCT and EMD had negative impact on the outcome of TLS-ERG patients; HCT
      could prolong OS, but could not overcome the poor prognostic impact of TLS-ERG.

PMID- 27874292
TI  - Granulocyte colony stimulating factor treatment of resistant thin endometrium in
      women with frozen-thawed blastocyst transfer.
AB  - : The aim of the study was to assess the granulocyte-colony stimulating factor (G
      CSF) effect on unresponsive thin (<7 mm) endometrium in women undergoing frozen
      thawed embryo transfer at the blastocyst stage. A total of 62 women with thin
      unresponsive endometrium were included in the study, of which, 29 received a G
      CSF infusion and 33 who opted out of the study served as controls. Patients in
      both groups had similar endometrial thickness at the time of the initial
      evaluation: 6.50 mm (5.50-6.80) in the G-CSF and 6.40 mm (5.50-7.0) in the
      control group. However, after the infusion endometrial thickness increased
      significantly in the G-CSF group in comparison with the controls (p=0.01),
      (Delta) 0.5 (0.02-1.2) (p=0.005). In the G-CSF group endometrium expanded to 7.90
      mm (6.58-8.70) while in the control group to 6.90 mm (6.0-7.75). Five women in
      each group conceived. The clinical pregnancy rate was 5/29 (17.24%) in the G-CSF
      treated group and 5/33 (15.15%) in the control group (p>0.05). The live birth
      rate was 2/29 (6.89%) in the G-CSF group and 2/33 (6.06%) in the control group
      (p>0.05). We concluded that G-CSF infusion leads to an improvement in endometrium
      thickness but not to any improvement in the clinical pregnancy and live birth
      rates. Until more data is available G-CSF treatment should be considered to be of
      limited value in increasing pregnancy rate. ABBREVIATIONS: G-CSF: granulocyte
      colony-stimulating factor; M-CSF: macrophagecolony-stimulating factor; GM-CSF:
      granulocyte-macrophage colony-stimulating factor; FET: frozen embryo transfer;
      IVF: in vitro fertilization.

PMID- 27874291
TI  - Zwitterionic structures: from physicochemical properties toward computer-aided
      drug designs.
AB  - Zwitterions, used widely in chemical, biological and medicinal fields, show
      distinct physicochemical properties relative to ordinary ampholytes, which
      largely decide their bioavailability and biological activities. In the present
      manuscript, these properties are discussed in order to facilitate our
      understanding of zwitterionic structures, followed by various examples of
      zwitterionic drugs and the critical role these properties play. We specifically
      focus our discussions on neuraminidase inhibitors (NAIs), which are used in the
      treatment and prevention of influenza, covering their computer-assisted design,
      transformation to zwitterionic isomers and interaction mechanisms of NAIs with
      proteins. The discovery and development of NAIs provide useful insights that may
      assist in the exploration of new zwitterionic drugs.

PMID- 27874293
TI  - Improved stability of solid dispersions of manidipine with polyethylene glycol
      4000/copovidone blends: application of ternary phase diagram.
AB  - CONTEXT: Manidipine (MDP) is generally used clinically as an antihypertensive
      agent; however, the bioavailability of orally administered MDP is limited due to
      their very low water solubility. OBJECTIVE: The objectives of this research were,
      therefore, to increase the solubility of MDP by the formation of ternary solid
      dispersions (tSD) with polyethylene glycol 4000 (PEG4000) and copovidone and to
      improve their stability. METHODS: Solid ternary phase diagram was constructed to
      find homogeneous solid dispersion region after melting and solidifying at low
      temperature with different quenching substances. The pulverized powder of solid
      dispersions was then determined, for their physicochemical properties, by
      differential scanning calorimetry, powder X-ray diffractometry, Fourier transform
      infrared (FTIR) spectroscopy and hot stage microscopy. The solubility and
      dissolution of MDP from the tSD were investigated. The physical stability of tSD
      was also determined under accelerated condition at 40  degrees C/75% relative
      humidity (RH) for 6 months. RESULTS AND DISCUSSION: The results showed that MDP
      was molecularly dispersed in PEG4000 and copovidone when the tSD was created from
      homogeneous region of solid ternary phase diagram. FTIR results confirmed that
      strong hydrogen bonding was presented between MDP and copovidone, leading to a
      significant increase in the solubility and dissolution of MDP. After storage at
      accelerated condition (40  degrees C/75%RH) for 6 months, the tSD still showed a
      good appearance and high solubility. CONCLUSION: The results of this study
      suggest that tSD prepared by melting has promising potential for oral
      administration and may be an efficacious approach for improving the therapeutic
      potential of MDP.

PMID- 27874294
TI  - Dacryoadenitis and extraocular muscle inflammation associated with contact lens
      related Acanthamoeba keratitis: A case report and review of the literature.
AB  - The present report discusses a new case of dacryoadenitis with extraocular muscle
      inflammation associated with Acanthamoeba keratitis (AK) in a contact lens
      wearer. A 41-year-old male, who has worn silicone hydrogel contact lenses on an
      extended basis for about 10 years, attended with the complaints of vision
      disturbance, hyperemia, and pain in his right eye. His history revealed that 1.5
      month ago, he had been diagnosed with allergic conjunctivitis and had used
      steroid eye drops. Biomicroscopic examination revealed eyelid edema, chemosis,
      and ring infiltration, radial keratoneuritis and an epithelial defect in the
      cornea. Magnetic resonance imaging demonstrated enlarged lacrimal gland with
      edematous changes consistent with inflammation due to dacryoadenitis. There were
      also thickening and edema of the right superior oblique and lateral rectus
      muscle. The treatment protocol for AK was applied with no specific treatment for
      dacryoadenitis. After 4 months of the treatment, dacryoadenitis and keratitis
      regressed. Dacryoadenitis and extraocular muscle inflammation may accompany AK
      more frequently than expected and previously known. The evaluation of the
      lacrimal gland and extraocular muscles in presence of AK might be beneficial for
      understanding better the exact clinical picture and course of the keratitis.

PMID- 27874295
TI  - Mechanism of low-level microwave radiation effect on nervous system.
AB  - The aim of this study is to explain the mechanism of the effect of low-level
      modulated microwave radiation on brain bioelectrical oscillations. The proposed
      model of excitation by low-level microwave radiation bases on the influence of
      water polarization on hydrogen bonding forces between water molecules, caused by
      this the enhancement of diffusion and consequences on neurotransmitters transit
      time and neuron resting potential. Modulated microwave radiation causes periodic
      alteration of the neurophysiologic parameters and parametric excitation of brain
      bioelectric oscillations. The experiments to detect logical outcome of the
      mechanism on physiological level were carried out on 15 human volunteers. The 450
      MHz microwave radiation modulated at 7, 40 and 1000 Hz frequencies was applied at
      the field power density of 0.16 mW/cm2. A relative change in the EEG power with
      and without radiation during 10 cycles was used as a quantitative measure.
      Experimental data demonstrated that modulated at 40 Hz microwave radiation
      enhanced EEG power in EEG alpha and beta frequency bands. No significant
      alterations were detected at 7 and 1000 Hz modulation frequencies. These results
      are in good agreement with the theory of parametric excitation of the brain
      bioelectric oscillations caused by the periodic alteration of neurophysiologic
      parameters and support the proposed mechanism. The proposed theoretical framework
      has been shown to predict the results of experimental study. The suggested
      mechanism, free of the restrictions related to field strength or time constant,
      is the first one providing explanation of low-level microwave radiation effects.

PMID- 27874296
TI  - CD44 mediates the catch-bond activated rolling of HEPG2Iso epithelial cancer
      cells on hyaluronan.
AB  - The attachment of cancer cells to the endothelium is an essential step during
      metastatic dissemination. The cell surface receptor CD44 is capable of binding to
      hyaluronan (HA) produced by tumor cells and by cells of the tumor
      microenvironment, including blood endothelial cells. Here, we investigated the
      role of CD44 in the interaction between the liver cancer cell line HepG2Iso and
      HA surfaces. The rolling interaction was quantitatively analyzed using a
      microfluidic shear force setup. It was found that rolling of the liver cancer
      cells on HA depends on CD44, which mediates a catch-bond interaction and thus a
      flow-induced rolling of the cells. Reduction of CD44 expression by means of
      siRNA, inhibition of the interaction of CD44 with HA by antibody blocking, and
      treatment with low molecular weight HA inhibited liver cancer cell rolling on HA
      coated surfaces. The results not only clearly show the dependency of the shear
      induced catch-bond interaction of HepG2Iso cells on CD44 and HA, but also for the
      first time demonstrate CD44-mediated rolling for epithelium-derived cells that
      are typically adherent.

PMID- 27874297
TI  - Organizational Infrastructure in the Collegiate Athletic Training Setting, Part
      I: Quality-of-Life Comparisons and Commonalities Among the Models.
AB  - CONTEXT:  Some anecdotal evidence has suggested that organizational
      infrastructure may affect the quality of life of athletic trainers (ATs).
      OBJECTIVE:  To compare ATs' perspectives on work-life balance, role strain, job
      satisfaction, and retention in collegiate practice settings within the various
      models. DESIGN:  Cross-sectional and qualitative study. SETTING:  National
      Collegiate Athletic Association Divisions I, II, and III. PATIENTS OR OTHER
      PARTICIPANTS:  Fifty-nine ATs from 3 models (athletics = 25, medical = 20,
      academic = 14) completed phase I. A total of 24 ATs (15 men, 9 women), 8 from
      each model, also completed phase II. DATA COLLECTION AND ANALYSIS:  Participants
      completed a Web-based survey for phase I and were interviewed via telephone for
      phase II. Quantitative data were analyzed using statistical software. Likert
      scale answers (1 = strongly disagree, 5 = strongly agree) to the survey questions
      were analyzed using the Kruskal-Wallis, Mann-Whitney U, and Cohen f tests.
      Qualitative data were evaluated using a general inductive approach. Multiple
      analyst triangulation and peer review were conducted to satisfy data credibility.
      RESULTS:  Commonalities were communication, social support, and time management
      and effective work-life balance strategies. Quantitative data revealed that ATs
      employed in the athletics model worked more hours (69.6 +/- 11.8 hours) than
      those employed in the medical (57.6 +/- 10.2 hours; P = .001) or academic (59.5
      +/- 9.5 hours; P = .02) model, were less satisfied with their pay (2.68 +/- 1.1;
      chi2 = 7.757, P = .02; f = 0.394), believed that they had less support from their
      administrators (3.12 +/- 1.1; chi2 = 9.512, P = .009; f = 0.443), and had fewer
      plans to remain in their current positions (3.20 +/- 1.2; chi2 = 7.134, P = .03;
      f = 0.374). Athletic trainers employed in the academic model believed that they
      had less support from coworkers (3.71 +/- 0.90; chi2 = 6.825, P = .03; f = 0.365)
      and immediate supervisors (3.43 +/- 0.90; chi2 = 6.006, P = .050; f = 0.340). No
      differences in role conflict were found among the models. CONCLUSIONS: 
      Organizational infrastructure may play a role in mediating various sources of
      conflict, but regardless of facilitators, ATs need to be effective communicators,
      have support networks in place, and possess time-management skills.

PMID- 27874300
TI  - Parent Training Curriculum for Children With Autism.

PMID- 27874298
TI  - Volitional Spine Stabilization During a Drop Vertical Jump From Different Landing
      Heights: Implications for Anterior Cruciate Ligament Injury.
AB  - CONTEXT: Volitional preemptive abdominal contraction (VPAC) during dynamic
      activities may alter trunk motion, but the role of the core musculature in
      positioning the trunk during landing tasks is unclear. OBJECTIVE: To determine
      whether volitional core-muscle activation incorporated during a drop vertical
      jump alters lower extremity kinematics and kinetics, as well as trunk and lower
      extremity muscle activity at different landing heights. DESIGN: Controlled
      laboratory study. SETTING: Clinical biomechanics laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Thirty-two young healthy adults, consisting of 17 men (age = 25.24
      +/- 2.88 years, height = 1.85 +/- 0.06 m, mass = 89.68 +/- 16.80 kg) and 15 women
      (age = 23.93 +/- 1.33 years, height = 1.67 +/- 0.08 m, mass = 89.68 +/- 5.28 kg).
      INTERVENTION(S): Core-muscle activation using VPAC. MAIN OUTCOME MEASURE(S): We
      collected 3-dimensional ankle, knee, and hip motions, moments, and powers; ground
      reaction forces; and trunk and lower extremity muscle activity during 0.30- and
      0.50-m drop vertical-jump landings. RESULTS: During landing from a 0.30-m height,
      VPAC performance increased external oblique and semitendinosis activity, knee
      flexion, and knee internal rotation and decreased knee-abduction moment and knee
      energy absorption. During the 0.50-m landing, the VPAC increased external oblique
      and semitendinosis activity, knee flexion, and hip flexion and decreased ankle
      inversion and hip-energy absorption. CONCLUSIONS: The VPAC performance during
      landing may protect the anterior cruciate ligament during different landing
      phases from different heights, creating a protective advantage just before ground
      contact and after the impact phase. Incorporating VPAC during high injury-risk
      activities may enhance pelvic stability, improve lower extremity positioning and
      sensorimotor control, and reduce anterior cruciate ligament injury risk while
      protecting the lumbar spine.

PMID- 27874301
TI  - Cognitive Predictors of Performance in Well-Trained Table Tennis Players With
      Intellectual Disability.
AB  - Evidence-based classification systems in Paralympic sport require knowledge of
      the underlying effect of impairment in a specific sport. This study investigated
      the relationship between cognition and tactical proficiency in 88 well-trained
      table tennis players with intellectual disability (ID; 29 women, 59 men, M +/- SD
      IQ 59.9 +/- 9.6). Data were collected at 3 competitions sanctioned by the
      International Federation for Para-Athletes with Intellectual Disabilities (INAS).
      A generic cognitive test consisting of 8 neuropsychological subtests was used to
      assess cognitive abilities relevant to sport (reaction time, processing speed,
      and decision speed; spatial visualization; fluid reasoning; memory; executive
      functioning; and visual processing). The backward stepwise-regression analysis
      model revealed that 18% of the variance in tactical proficiency was attributed to
      spatial visualization and simple reaction time. Applications of these findings
      resulted in an evidence-based classification system that led to the reinclusion
      of athletes with ID in Paralympic table tennis and provide the basis for future
      research in this important area.

PMID- 27874302
TI  - Sprint Performance of Elite Wheelchair Basketball Players: Applicability of a
      Laser System for Describing the Velocity Curve.
AB  - The purpose of this study was to develop a methodology to accurately analyze
      sprint performance of elite wheelchair basketball (WB) players in their own
      training context using a laser system and to analyze the velocity curve performed
      by the players regarding their functional classification and their playing
      position. Twelve WB players, from the Spanish men's national team, took part in
      an oncourt 20-m-sprint test. BioLaserSport(r) was used to obtain time, mean
      velocities (Vm), maximum velocities (Vmax), and distances at 90%, 95%, and 98% of
      their Vmax. Vm and Vmax reached high values in Classes II and III and in the
      guard playing position. The protocol developed with the laser system makes it
      possible to obtain a precise velocity curve in short sprints and allows easy
      analysis of decisive kinematic performance variables in WB players, showing
      immediate feedback to coaches and players. The normalized data allow an
      interpretation of how much, where, and when Vmax occurs along the test.

PMID- 27874303
TI  - Physical Activity Patterns in Youth With Intellectual Disabilities.
AB  - The aim of this study was to assess the physical activity (PA) patterns of youth
      with intellectual disabilities (ID). PA was monitored for 7 days in 70
      participants, 5-15 years old, using accelerometers. There were 32 participants
      included in the final analysis. Habitual PA and the number of continuous bouts
      accrued for a range of bout lengths (5-600 s) for light (LPA), moderate (MPA),
      and vigorous (VPA) PA were calculated. Multivariate analysis of covariance was
      used to assess differences in the number of continuous bouts by sex, age, and ID
      group and between week and weekend days. Participants exhibited short sporadic
      bursts of activity. The number of continuous bouts decreased as the intensity and
      duration increased. Few differences in PA patterns were reported by sex, ID
      group, and age group and between week and weekend days, possibly due to the
      generally low PA levels in this population.

PMID- 27874299
TI  - Cooling Effectiveness of a Modified Cold-Water Immersion Method After Exercise
      Induced Hyperthermia.
AB  - CONTEXT:  Recommended treatment for exertional heat stroke includes whole-body
      cold-water immersion (CWI). However, remote locations or monetary or spatial
      restrictions can challenge the feasibility of CWI. Thus, the development of a
      modified, portable CWI method would allow for optimal treatment of exertional
      heat stroke in the presence of these challenges. OBJECTIVE:  To determine the
      cooling rate of modified CWI (tarp-assisted cooling with oscillation [TACO])
      after exertional hyperthermia. DESIGN:  Randomized, crossover controlled trial.
      SETTING:  Environmental chamber (temperature = 33.4 degrees C +/- 0.8 degrees C,
      relative humidity = 55.7% +/- 1.9%). PATIENTS OR OTHER PARTICIPANTS:  Sixteen
      volunteers (9 men, 7 women; age = 26 +/- 4.7 years, height = 1.76 +/- 0.09 m,
      mass = 72.5 +/- 9.0 kg, body fat = 20.7% +/- 7.1%) with no history of compromised
      thermoregulation. INTERVENTION(S):  Participants completed volitional exercise
      (cycling or treadmill) until they demonstrated a rectal temperature (Tre) >=39.0
      degrees C. After exercise, participants transitioned to a semirecumbent position
      on a tarp until either Tre reached 38.1 degrees C or 15 minutes had elapsed
      during the control (no immersion [CON]) or TACO (immersion in 151 L of 2.1
      degrees C +/- 0.8 degrees C water) treatment. MAIN OUTCOME MEASURE(S):  The Tre,
      heart rate, and blood pressure (reported as mean arterial pressure) were assessed
      precooling and postcooling. Statistical analyses included repeated-measures
      analysis of variance with appropriate post hoc t tests and Bonferroni correction.
      RESULTS:  Before cooling, the Tre was not different between conditions (CON:
      39.27 degrees C +/- 0.26 degrees C, TACO: 39.30 degrees C +/- 0.39 degrees C; P =
      .62; effect size = -0.09; 95% confidence interval [CI] = -0.2, 0.1). At
      postcooling, the Tre was decreased in the TACO (38.10 degrees C +/- 0.16 degrees
      C) compared with the CON condition (38.74 degrees C +/- 0.38 degrees C; P < .001;
      effect size = 2.27; 95% CI = 0.4, 0.9). The rate of cooling was greater during
      the TACO (0.14 +/- 0.06 degrees C/min) than the CON treatment (0.04 degrees C/min
      +/- 0.02 degrees C/min; t15 = -8.84; P < .001; effect size = 2.21; 95% CI = 
      0.13, -0.08). These differences occurred despite an insignificant increase in
      fluid consumption during exercise preceding CON (0.26 +/- 0.29 L) versus TACO
      (0.19 +/- 0.26 L; t12 = 1.73; P = .11; effect size = 0.48; 95% CI = -0.02, 0.14)
      treatment. Decreases in heart rate did not differ between the TACO and CON
      conditions (t15 = -1.81; P = .09; effect size = 0.45; 95% CI = -22, 2). Mean
      arterial pressure was greater at postcooling with TACO (84.2 +/- 6.6 mm Hg) than
      with CON (67.0 +/- 9.0 mm Hg; P < .001; effect size = 2.25; 95% CI = 13, 21).
      CONCLUSIONS:  The TACO treatment provided faster cooling than did the CON
      treatment. When location, monetary, or spatial restrictions are present, TACO
      represents an effective alternative to traditional CWI in the emergency treatment
      of patients with exertional hyperthermia.

PMID- 27874304
TI  - Improving Paralympic Development Programs: Athlete and Institutional Pathways and
      Organizational Quality Indicators.

PMID- 27874305
TI  - Paralympic Legacy: Exploring the Impact of the Games on the Perceptions of Young
      People With Disabilities.
AB  - The London 2012 Olympic and Paralympic Games aimed to deliver a legacy to
      citizens of the United Kingdom, which included inspiring a generation of young
      people to participate in sport. This study aimed to understand the legacy of the
      Paralympic Games for children with disabilities. Eight adolescents (11-16 yr)
      with physical disabilities were interviewed about their perceptions of the
      Paralympic Games. Thematic analysis found 3 key themes that further our
      understanding of the Paralympic legacy. These were Paralympians as role models,
      changing perceptions of disability, and the motivating nature of the Paralympics.
      Findings demonstrate that the Games were inspirational for children with
      disabilities, improving their self-perceptions. This is discussed in relation to
      previous literature, and core recommendations are made.

PMID- 27874306
TI  - Power and Speed Differences Between Brazilian Paralympic Sprinters With Visual
      Impairment and Their Guides.
AB  - This study compared the physical performance of Paralympic sprinters with visual
      impairments (PSVI) and their guides in jump and sprint tests. Ten PSVI and guides
      executed squat jumps (SJ), countermovement jumps (CMJ), horizontal quintuple
      right/left-leg jumps (QR/QL), decuple jumps (DEC), and 50-m-sprint tests. The
      guides were superior to the PSVI in SJ (35.9 +/- 6.3 vs 45.6 +/- 3.2 cm), CMJ
      (38.5 +/- 6.2 vs 46.7 +/- 4.0 cm), QR (9.2 +/- 1.9 vs 12.7 +/- 1.0 m), QL (9.4 +/
      1.9 vs 13.1 +/- 0.8 m), DEC (21.0 +/- 3.3 vs. 27.2 +/- 1.7 m), and 50-m sprints
      (8.4 +/- 0.4 vs 7.6 +/- 0.5 m/s). The average differences between the PSVI and
      guides in the sprint tests was 10%, range 1-24%. Therefore, substantial
      differences in sprinting speed (in favor of the guides) between the peers were
      observed. Coaches should develop strategies to train the guides to improve their
      muscle-power performance.

PMID- 27874307
TI  - Single-center, single-dose, open-label, randomized, two-period crossover study on
      the bioavailability of methotrexate administered using a novel prefilled, needle
      free delivery system.
AB  - OBJECTIVE: Zeneo 1 is a needle-free injection device. We performed a
      pharmacokinetic study to investigate the bioequivalence of methotrexate
      administered subcutaneously using either the needle-free injection device or a
      conventional needle and syringe. RESEARCH DESIGN AND METHODS: This was a single
      dose, open-label, laboratory-blind, randomized crossover study performed in adult
      healthy volunteers. Each participant received two methotrexate injections (each
      25 mg), one via needle-free injection device and one via conventional injection,
      with a 21-28 day wash-out interval between dosing. For each participant, the
      administration site for both injections was either the abdomen or the thigh. MAIN
      OUTCOME MEASURES: The primary pharmacokinetic outcome parameters were AUC(0-t)
      and Cmax. Bioequivalence was assessed by standard criteria: whether 90%
      confidence intervals of geometric mean ratios for the two administration methods
      were within 80-125%. RESULTS: Fifty-two individuals completed the study.
      Bioequivalence criteria were met for AUC(0-t), for the overall analysis (both
      injection sites: 90% confidence interval: 99.4-103.1%), and for each injection
      site separately. Bioequivalence was similarly demonstrated with AUC(0-infinity).
      Bioequivalence criteria for Cmax were fulfilled for abdominal administration but
      not for the overall analysis. Injection via the needle-free injection device was
      well tolerated. LIMITATIONS: Limitations include conducting the study in healthy
      volunteers and the relatively small subject number (albeit satisfactory for
      bioequivalence). CONCLUSIONS: This study shows that methotrexate injection via
      needle-free injection device is bioequivalent to a conventional needle and
      syringe in relation to AUC(0-t) and AUC(0-infinity). Studies of needle-free
      injection device use in patients requiring methotrexate therapy are planned.

PMID- 27874309
TI  - Abundance and Characterization of Perfect Microsatellites on the Cattle Y
      Chromosome.
AB  - Microsatellites or simple sequence repeats (SSRs) are found in most organisms and
      play an important role in genomic organization and function. To characterize the
      abundance of SSRs (1-6 base-pairs [bp]) on the cattle Y chromsome, the relative
      frequency and density of perfect or uninterrupted SSRs based on the published Y
      chromosome sequence were examined. A total of 17,273 perfect SSRs were found,
      with total length of 324.78 kb, indicating that approximately 0.75% of the cattle
      Y chromosome sequence (43.30 Mb) comprises perfect SSRs, with an average length
      of 18.80 bp. The relative frequency and density were 398.92 loci/Mb and 7500.62
      bp/Mb, respectively. The proportions of the six classes of perfect SSRs were
      highly variable on the cattle Y chromosome. Mononucleotide repeats had a total
      number of 8073 (46.74%) and an average length of 15.45 bp, and were the most
      abundant SSRs class, while the percentages of di-, tetra-, tri-, penta-, and hexa
      nucleotide repeats were 22.86%, 11.98%, 11.58%, 6.65%, and 0.19%, respectively.
      Different classes of SSRs varied in their repeat number, with the highest being
      42 for dinucleotides. Results reveal that repeat categories A, AC, AT, AAC, AGC,
      GTTT, CTTT, ATTT, and AACTG predominate on the Y chromosome. This study provides
      insight into the organization of cattle Y chromosome repetitive DNA, as well as
      information useful for developing more polymorphic cattle Y-chromosome-specific
      SSRs.

PMID- 27874310
TI  - Ancient microRNA families that regulate transcription factors are preferentially
      preserved during plant radiation.
AB  - Essential genes are usually less likely to be lost during evolution, whereas
      dispensable genes are lost more frequently. Integrating sacred lotus and other
      plant microRNA (miRNA) data, we found different ancient miRNA families that arose
      before eudicot radiation exhibit different evolutionary trajectories. Those
      ancient miRNA families with higher copy and target numbers, and older age are
      more likely to be retained in plant descendants and more conserved in (hairpin
      structured) miRNA gene sequences. Interestingly, a large portion of the well
      conserved miRNA families in plant lineages can target transcription factors
      (TFs). Also, we found miRNA families that target TFs are preferentially retained
      after sacred lotus genome duplication. In this article, we provide some points to
      discuss why miRNA families that regulate TFs are more likely to be preserved in
      plants.

PMID- 27874308
TI  - Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse
      model of colitis induced by T-synthase deficiency.
AB  - Intestinal dysbiosis is thought to confer susceptibility to inflammatory bowel
      disease (IBD), but it is unknown whether dynamic changes in the microbiome
      contribute to fluctuations in disease activity. We explored this question using
      mice with intestine-specific deletion of C1galt1 (also known as T-synthase) (Tsyn
      mice). These mice develop spontaneous microbiota-dependent colitis with a
      remitting/relapsing course due to loss of mucin core-1 derived O-glycans. 16S
      rRNA sequencing and untargeted metabolomics demonstrated age-specific
      perturbations in the intestinal microbiome and metabolome of Tsyn mice compare
      with littermate controls at weeks 3 (disease onset), 5 (during remission), and 9
      (after relapse). Colitis remission corresponded to increased levels of
      FoxP3+RORgammat+CD4+ T cells in the colonic lamina propria that were positively
      correlated with operational taxonomic units (OTUs) in the S24-7 family and
      negatively correlated with OTUs in the Clostridiales order. Relapse was
      characterized by marked expansion of FoxP3-RORgammat+CD4+ T cells expressing
      IFNgamma and IL17A, which were associated with Clostridiales OTUs distinct from
      those negatively correlated with FoxP3+RORgammat+CD4+ T cells. Our findings
      suggest that colitis remission and relapse in the Tsyn model may reflect
      alterations in the microbiome due to reduced core-1 O-glycosylation that shift
      the balance of regulatory and pro-inflammatory T cell subsets. We investigated
      whether genetic variation in C1galt1 correlated with the microbiome in a cohort
      of 78 Crohn's disease patients and 101 healthy controls. Polymorphisms near
      C1galt1 (rs10486157) and its molecular chaperone, Cosmc (rs4825729), were
      associated with altered composition of the colonic mucosal microbiota, supporting
      the relevance of core-1 O-glycosylation to host regulation of the microbiome.

PMID- 27874311
TI  - Long-term persistence in protection and response to a hepatitis B vaccine booster
      among adolescents immunized in infancy in the western region of China.
AB  - OBJECTIVES: To evaluate the persistence of protection from hepatitis B (HB)
      vaccination among adolescents immunized with a primary series of HB vaccine as
      infants, and the immune response to booster doses. METHODS: Healthy adolescents
      aged 15-17 y vaccinated with HB vaccine only at birth were enrolled. Baseline
      serum hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface
      antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were
      detected by Enzyme-Linked Immunosorbent Assay (ELISA) and anti-HBs level was
      measured using Chemiluminescent Microparticle Immunoassay (CMIA). The rate of HBV
      infection was calculated. The seroprotection rate of anti-HBs (>= 10 mIU/ml) and
      GMC level were used to evaluate the persistence of immunity from HB vaccination.
      Those with anti-HBs < 10 mIU/ml were immunized with booster doses of HB vaccine
      and the anamnestic response was assessed. RESULTS: Of 180 adolescents who
      received a primary series of HB vaccinations as infants, 3 (1.7%) had HBV
      infection and 74 (41.1%) had anti-HBs >= 10 mIU/ml with a GMC of 145.11 mIU/ml.
      The remaining 103 (57.2%) with anti-HBs < 10 mIU/ml received a booster dose of 20
      MUg HB vaccine and achieved the seroprotection rate of 84% (84/100) and a GMC of
      875.19 mIU/ml at one month post-booster. An additional dose of 60 MUg HB vaccine
      was administered to the 16 adolescents with anti-HBs < 10 mIU/ml after the first
      booster. All of them obtained anti-HBs seroprotection with a GMC of 271.02 mIU/ml
      at 1.5 months after an additional dose. CONCLUSIONS: Vaccine-induced immunity
      persisted for up to 15-17 y in 89.3% (158/177) of participants after a primary HB
      vaccination in infancy. Administering a booster dose of 20MUg HB vaccine elicited
      an anamnestic immune responses in the majority of individuals with baseline anti
      HBs <10 mIU/ml.

PMID- 27874313
TI  - Belief in miracles and attitudes towards voluntary euthanasia.
AB  - Results of logistic regression analysis of data from the General Social Survey (N
      = 1,799) find that those who have a strong belief in miracles are more likely to
      say that a person with an incurable illness should not be allowed to accept
      medical treatments that painlessly hasten death than those who have a less strong
      belief in miracles or do not believe in miracles, net of respondents' religious
      affiliations, frequency of religious attendance, views of the Bible, and other
      sociodemographic controls. Results highlight the need to consider specific
      religious beliefs when predicting individuals' attitudes towards voluntary
      euthanasia.

PMID- 27874314
TI  - Optimal control and cost effectiveness analysis for Newcastle disease eco
      epidemiological model in Tanzania.
AB  - In this paper, a deterministic compartmental eco- epidemiological model with
      optimal control of Newcastle disease (ND) in Tanzania is proposed and analysed.
      Necessary conditions of optimal control problem were rigorously analysed using
      Pontryagin's maximum principle and the numerical values of model parameters were
      estimated using maximum likelihood estimator. Three control strategies were
      incorporated such as chicken vaccination (preventive), human education campaign
      and treatment of infected human (curative) and its' impact were graphically
      observed. The incremental cost effectiveness analysis technique used to determine
      the most cost effectiveness strategy and we observe that combination of chicken
      vaccination and human education campaign strategy is the best strategy to
      implement in limited resources. Therefore, ND can be controlled if the farmers
      will apply chicken vaccination properly and well in time.

PMID- 27874312
TI  - Momilactone B Inhibits Ketosis In Vitro by Regulating the ANGPTL3-LPL Pathway and
      Inhibiting HMGCS2.
AB  - Ketogenesis is the production of ketone bodies, which provide energy when the
      body lacks glucose. Under ketogenic conditions, the body switches from primarily
      carbohydrate to fat metabolism to maintain energy balance. However, accumulation
      of high levels of ketone bodies in the blood results in ketosis. Treating ketosis
      with natural substances is preferable, because they are unlikely to cause side
      effects. Momilactone B is an active compound isolated from Korean rice. Based on
      previous studies, we hypothesized that momilactone B could inhibit ketosis. We
      constructed an in vitro ketosis model by glucose starvation. We used this model
      to test the anti-ketosis effects of momilactone B. A primary target for treating
      ketosis is angiopoietin-like-3 (ANGPTL3), which modulates lipoprotein metabolism
      by inhibiting lipoprotein lipase (LPL), a multifunctional enzyme that breaks down
      stored fat to produce triglycerides. We showed that momilactone B could regulate
      the ANGPTL3-LPL pathway. However, a strong anti-ketosis candidate drug should
      also inhibit ketogenesis. Ketogenesis can be suppressed by inhibiting the
      expression of 3-hydroxy-3-methylglutaryl-CoA synthase-2 (HMGCS2), a mitochondrial
      enzyme that converts acetyl-CoA to ketone bodies. We found that momilactone B
      suppressed the expression of HMGCS2 through the increased expression of STAT5b.
      We also elucidated the relationship of STAT5b to ANGPTL3 and LPL expression.

PMID- 27874315
TI  - A review of Cognitive neuroscience: A very short introduction.

PMID- 27874316
TI  - Extra views on structure and dynamics of DNA loops on nucleosomes studied with
      molecular simulations.
AB  - It has been shown experimentally that the action of the RSC chromatin remodeler
      leads to the formation of an irregular, partially remodeled nucleosome, termed a
      remosome. The remosome contains an extra 30-40 base pairs of DNA compared to a
      canonical nucleosome. Large-scale molecular simulations have provided information
      on the probable structure of remosomes and have explained why they remain stable
      in the absence of RSC. Here we explain how these simulations were carried out and
      what the resulting remosome models imply in terms of the mechanism of action of
      RSC. We notably show that local kinks within DNA are key in explaining how extra
      DNA can be in added to nucleosomes without unduly disturbing DNA-histone binding.

PMID- 27874317
TI  - Within-culture variation in the content of stereotypes: Application and
      development of the stereotype content model in an Eastern European culture.
AB  - There is little and unsystematic evidence about whether the content of
      stereotypes can vary within a culture. Using the Stereotype Content Model (SCM)
      as a theoretical framework, in two studies we examined the content of stereotypes
      in an Eastern European culture, namely Romania. Data were collected from four
      regions prototypical in terms of economic and social development in Romania, and
      we examined whether the content of stereotypes varies across these regions. As
      expected, the findings confirm the applicability of the SCM in Romania to reveal
      culture-specific stereotypes and provide initial support for within-culture
      variation in the content of stereotypes. We discuss, in particular, possible
      reasons for two main findings: a strong one-dimensional structure of stereotypes,
      and regional differences in stereotype content.

PMID- 27874318
TI  - A study with Bangladeshi women: Seeking care for breast health.
AB  - In many low- and middle-income countries, breast cancer survival is low. Reasons
      for this are multifactorial, but delayed presentation for care is a common theme.
      In this survey study with 100 urban Bangladeshi women, we examined the role of
      socioeconomic and sociocultural factors on their likelihood to seek breast care
      from a family physician. In our multivariate model, a woman's age and education
      significantly predicted her likelihood to see a physician. Sociocultural aspects
      (e.g., concerns about time commitment of family members, personal household
      obligations) were significant at bivariate level. Findings are discussed in
      relation to practice, policy, and research.

PMID- 27874319
TI  - Grandiose and Vulnerable Narcissism, Materialism, Money Attitudes, and
      Consumption Preferences.
AB  - Narcissism is increasingly being investigated in the context of consumer
      attitudes and behavior. Previous research showed that narcissism is reflected in
      materialistic tendencies and money-related attitudes. However, almost all of
      these studies concerned the grandiose type of narcissism. We examined
      relationships of both grandiose and vulnerable narcissism with materialism, money
      attitudes, and consumption preferences in a nonstudent sample. The results showed
      that the two types of narcissism are equally associated with materialism and a
      tendency to conspicuous (public) consumption. Differences between grandiose and
      vulnerable narcissism with regard to money attitudes were observed. Materialism
      mediated most of the relationships between narcissism, money attitudes, and
      consumption preferences, but the patterns of mediation were different for
      grandiose and vulnerable subtypes. Mutual suppression occurred when grandiose
      narcissism and materialism predicted anxiety associated with money and when
      vulnerable narcissism and materialism predicted money perceived as a source of
      evil. The results suggested that not only grandiose, but also vulnerable
      narcissists may be prone to excessive consumption and that this can be explained
      by their materialistic tendencies.

PMID- 27874321
TI  - The blocking effect in associative learning involves learned biases in rapid
      attentional capture.
AB  - Blocking refers to the finding that less is learned about the relationship
      between a stimulus and an outcome if pairings are conducted in the presence of a
      second stimulus that has previously been established as a reliable predictor of
      that outcome. Attentional models of associative learning suggest that blocking
      reflects a reduction in the attention paid to the blocked cue. We tested this
      idea in three experiments in which participants were trained in an associative
      learning task using a blocking procedure. Attention to stimuli was measured 250
      ms after onset using an adapted version of the dot probe task. This task was
      presented at the beginning of each learning trial (Experiments 1 and 2) or in
      independent trials (Experiment 3). Results show evidence of reduced attention to
      blocked stimuli (i.e. "attentional blocking"). In addition, this attentional bias
      correlated with the magnitude of blocking in associative learning, as measured by
      predictive-value judgments. Moreover, Experiments 2 and 3 found evidence of an
      influence of learning about predictiveness on memory for episodes involving
      stimuli. These findings are consistent with a central role of learned attentional
      biases in producing the blocking effect, and in the encoding of new memories.

PMID- 27874320
TI  - A consensual qualitative research analysis of the experience of inmate hospice
      caregivers: Posttraumatic growth while incarcerated.
AB  - A growing number of correctional facilities train inmates to provide end-of-life
      care for dying inmates. This study explores the phenomenological perspective of
      inmate-caregivers participating in an inmate-facilitated hospice program (IFHP)
      with regard to meaning and purpose in life, attitudes on death and dying, and
      perceived personal impact of participation. Twenty-two inmate-caregivers were
      interviewed at a maximum-security state correctional facility in the United
      States. The interviews were transcribed verbatim and analyzed using the
      Consensual Qualitative Research Methodology. Results suggest that participating
      in an IFHP may facilitate personal growth and transformation that mirrors the
      tenets of posttraumatic growth.

PMID- 27874322
TI  - The Relations Between Patterning, Executive Function, and Mathematics.
AB  - Patterning, or the ability to understand patterns, is a skill commonly taught to
      young children as part of school mathematics curricula. It seems likely that some
      aspects of executive function, such as cognitive flexibility, inhibition, and
      working memory, may be expressed in the patterning abilities of children. The
      primary objective of the present study was to examine the relationship between
      patterning and executive functioning for first grade children. In addition, the
      relations between patterning, executive functioning, mathematics, and reading
      were examined. The results showed that patterning was significantly related to
      cognitive flexibility and working memory, but not to inhibition. Patterning,
      cognitive flexibility, and working memory were significantly related to
      mathematical skills. Only patterning and working memory were significantly
      related to reading. Regression analyses and structural equation modeling both
      showed that patterning had effects on both reading and mathematics measures, and
      that the effects of cognitive flexibility were entirely mediated by patterning.
      Working memory had independent effects on reading and mathematics, and also
      effects moderated by patterning. In sum, these findings suggest that cognitive
      flexibility and working memory are related to patterning and express their
      effects on reading and mathematics in whole or in part through patterning.

PMID- 27874323
TI  - Flotation of Toxocara canis Eggs in Commercial Bleach and Effects of Bleach
      Treatment Times on Larval Development in These Eggs.
AB  - Toxocara canis is a common intestinal nematode of young dogs. Puppies contaminate
      the environment with large numbers of eggs that can embryonate and become
      infective in less than a month. Embryonated eggs are infectious for humans and
      other paratenic hosts. Most T. canis infections in humans are asymptomatic;
      however, migration of T. canis larvae in the eye and in the central nervous
      system can result in vision loss, blindness, and even death. The eggs of T. canis
      are highly resistant to harsh environmental conditions and routinely used
      chemical disinfectants. The objective of this study was to evaluate the effects
      of full-strength commercial bleach (5.25% sodium hypochlorite solution) treatment
      on development of T. canis eggs and to report our serendipitous finding that T.
      canis eggs in dog feces can float in passive fecal flotation tests using bleach.
      We also demonstrated that T. canis eggs could be identified using the McMaster's
      fecal eggs counting test using 100% bleach. Toxocara canis eggs collected from
      the feces of naturally infected 4-8 wk old puppies were treated with full
      strength bleach (5.25% sodium hypochlorite solution) for 15 min, 30 min, 60 min,
      and 120 min; washed free of bleach smell by centrifugation; and resuspended in
      0.1 N sulfuric acid solution to undergo larval development at room temperature
      for 18 days after exposure to bleach. Motile larvae were observed in T. canis
      eggs in all groups treated for 15-120 min and eggs continuously exposed to bleach
      for 18 days. Our results indicate that bleach may not be an appropriate
      disinfectant for dog kennels, cages, or laboratory utensils and work surfaces.
      Toxocara canis eggs are resistant to bleach treatment and continue to pose a risk
      for canine and human infections. Further study is needed to find the most
      appropriate methods for disinfection and removal of eggs to reduce the risk of
      transmission of this parasite.

PMID- 27874324
TI  - Interaction between Radioadaptive Response and Radiation-Induced Bystander Effect
      in Caenorhabditis elegans : A Unique Role of the DNA Damage Checkpoint.
AB  - Although radioadaptive responses (RAR) and radiation-induced bystander effects
      (RIBE) are two important biological effects of low-dose radiation, there are
      currently only limited data that directly address their interaction, particularly
      in the context of whole organisms. In previous studies, we separately
      demonstrated RAR and RIBE using an in vivo system of C. elegans . In the current
      study, we further investigated their interaction in C. elegans , with the ratio
      of protruding vulva as the biological end point for RAR. Fourteen-hour-old worms
      were first locally targeted with a proton microbeam, and were then challenged
      with a high dose of whole-body gamma radiation. Microbeam irradiation of the
      posterior pharynx bulbs and rectal valves of C. elegans could significantly
      suppress the induction of protruding vulva by subsequent gamma irradiation,
      suggesting a contribution of RIBE to RAR in the context of the whole organism.
      Moreover, C. elegans has a unique DNA damage response in which the upstream DNA
      damage checkpoint is not active in most of somatic cells, including vulval cells.
      However, its impairment in atm-1 and hus-1 mutants blocked the RIBE-initiated RAR
      of vulva. Similarly, mutations in the atm-1 and hus-1 genes inhibited the RAR of
      vulva initiated by microbeam irradiation of the vulva itself. These results
      further confirm that the DNA damage checkpoint participates in the induction of
      RAR of vulva in C. elegans in a cell nonautonomous manner.

PMID- 27874325
TI  - Mixed Beam Murine Harderian Gland Tumorigenesis: Predicted Dose-Effect
      Relationships if neither Synergism nor Antagonism Occurs.
AB  - Complex mixed radiation fields exist in interplanetary space, and little is known
      about their late effects on space travelers. In silico synergy analysis default
      predictions are useful when planning relevant mixed-ion-beam experiments and
      interpreting their results. These predictions are based on individual dose-effect
      relationships (IDER) for each component of the mixed-ion beam, assuming no
      synergy or antagonism. For example, a default hypothesis of simple effect
      additivity has often been used throughout the study of biology. However, for more
      than a century pharmacologists interested in mixtures of therapeutic drugs have
      analyzed conceptual, mathematical and practical questions similar to those that
      arise when analyzing mixed radiation fields, and have shown that simple effect
      additivity often gives unreasonable predictions when the IDER are curvilinear.
      Various alternatives to simple effect additivity proposed in radiobiology,
      pharmacometrics, toxicology and other fields are also known to have important
      limitations. In this work, we analyze upcoming murine Harderian gland (HG) tumor
      prevalence mixed-beam experiments, using customized open-source software and
      published IDER from past single-ion experiments. The upcoming experiments will
      use acute irradiation and the mixed beam will include components of high atomic
      number and energy (HZE). We introduce a new alternative to simple effect
      additivity, "incremental effect additivity", which is more suitable for the HG
      analysis and perhaps for other end points. We use incremental effect additivity
      to calculate default predictions for mixture dose-effect relationships, including
      95% confidence intervals. We have drawn three main conclusions from this work. 1.
      It is important to supplement mixed-beam experiments with single-ion experiments,
      with matching end point(s), shielding and dose timing. 2. For HG tumorigenesis
      due to a mixed beam, simple effect additivity and incremental effect additivity
      sometimes give default predictions that are numerically close. However, if
      nontargeted effects are important and the mixed beam includes a number of
      different HZE components, simple effect additivity becomes unusable and another
      method is needed such as incremental effect additivity. 3. Eventually, synergy
      analysis default predictions of the effects of mixed radiation fields will be
      replaced by more mechanistic, biophysically-based predictions. However,
      optimizing synergy analyses is an important first step. If mixed-beam experiments
      indicate little synergy or antagonism, plans by NASA for further experiments and
      possible missions beyond low earth orbit will be substantially simplified.

PMID- 27874489
TI  - Multiple sclerosis e-registries.

PMID- 27874490
TI  - Symptom tracking: from clinically isolated syndrome to advanced multiple
      sclerosis.

PMID- 27874326
TI  - Alcohol use patterns and alcohol use disorders among young adult, ethnically
      diverse bariatric surgery patients.
AB  - BACKGROUND: Research suggests that young adults and racial/ethnic minorities are
      at an increased risk for problematic alcohol use. Recent studies have also
      documented patterns of problematic alcohol use among a subset of weight loss
      surgery (WLS) patients. However, to date, there are no published studies
      investigating the intersection of these demographic and clinical characteristics.
      METHODS: This study used descriptive and inferential analyses to examine alcohol
      use patterns, prevalence of pre- and post-WLS alcohol use disorders (AUDs), and
      predictors of increased alcohol use and problematic alcohol use post-WLS among
      young adult (mean age 26.5 years, SD = 5.5 years) ethnically diverse (57%
      Hispanic, 28% non-Hispanic black) WLS patients (N = 69). RESULTS: Over 21% of the
      sample had a history of a lifetime AUD, and 4.2% of the sample developed an AUD
      post-WLS. In the past 30 days, 14.5% of respondents reported binge drinking, and
      42% reported drinking until intoxication. History of a pre-WLS AUD was associated
      with an increased frequency of alcohol use post-WLS (P = .012). Age, time since
      WLS, the gastric bypass procedure, and pre-WLS history of an AUD were not
      significant predictors of binge drinking or drinking to intoxication post-WLS.
      CONCLUSIONS: Ethnically diverse, young adults may have an elevated prevalence of
      AUD diagnoses pre-WLS. Having a pre-WLS AUD appears to be a risk factor for
      increased alcohol use post-WLS. Young adult WLS patients might also demonstrate
      high rates of binge drinking and drinking to intoxication. Binge drinking could
      be especially problematic considering that WLS could increase sensitivity to
      alcohol. Further investigation is warranted with this important subpopulation to
      explore risk factors for problematic alcohol use post-WLS; future assessments of
      alcohol use should consider potential heightened alcohol sensitivity resulting
      from WLS.

PMID- 27874491
TI  - Movement disorders in multiple sclerosis and their treatment.
AB  - Hyperkinetic movement disorders such as tremors are not uncommon in patients with
      multiple sclerosis (MS). The classical feature is intention tremor, whereas rest
      tremors appear not to occur. Treatment is mainly invasive, with options of Gamma
      Knife surgery, thalamotomy or deep brain stimulation depending on individual
      circumstances. Deep brain stimulation is the only option for patients who require
      a bilateral intervention. All treatment recommendations have only low evidence.
      Tremors can also be cured spontaneously by a subsequent strategic MS lesion.
      Paroxysmal dyskinesias are rarer than tremors. The rarest MS movement disorder is
      symptomatic paroxysmal choreoathetosis, tonic spasms or 'brain stem fits';
      attacks are short but frequent, up to 200 per day and generally respond well to
      carbamazepine.

PMID- 27874492
TI  - An update on MS Nurse PROfessional, an ongoing project of the European Multiple
      Sclerosis Platform.
AB  - Within the multidisciplinary team required to manage people with multiple
      sclerosis (MS) effectively, the nurse is the central component of coordinated
      care and support. A 2009 survey led by the European Multiple Sclerosis Platform,
      an umbrella organization of national MS associations, identified variance and
      disparity across Europe in the nursing care of MS patients. This led to
      development of MS Nurse PROfessional, a continuing medical education-accredited
      modular online learning program endorsed and approved by leading international
      nursing and professional groups, and people with MS, as a tool to support the
      evolving role of the European MS nurse. Analysis of participant experience and
      nurse practice to date has been overwhelmingly positive. Expansion of MS Nurse
      PRO is underway or planned for future.

PMID- 27874493
TI  - Web-based medical and health information in multiple sclerosis: for patients and
      physicians.

PMID- 27874494
TI  - Pediatric multiple sclerosis: updates in epidemiology, clinical features and
      management.
AB  - Consensus definitions for acute demyelinating syndromes in children have led to
      increased recognition of pediatric multiple sclerosis and improved our
      understanding of its pathogenesis, epidemiology and treatment. An estimated 2-10%
      of MS patients experience their first clinical symptom in childhood. Multiple
      genetic and environmental risk factors have been identified in the pathogenesis
      of pediatric MS, although further research to determine their interplay is
      required. Clinical trials of emerging disease-modifying therapies in children are
      nearing completion. Additional treatment options are expected to bring associated
      challenges. As pediatric MS remains relatively uncommon overall, international
      collaboration is essential to facilitate research.

PMID- 27874496
TI  - 2016 Multiple Sclerosis Experts Summit: Foreword.

PMID- 27874495
TI  - Evolution of multiple sclerosis spasticity-associated symptoms: latest data.
AB  - In addition to muscle stiffness and increasing mobility restrictions, symptoms
      commonly associated with multiple sclerosis (MS) spasticity are spasms, sleep
      disturbances, pain, fatigue and bladder dysfunction. Treatment options include
      trigger factor avoidance, physiotherapy and antispasticity medication. Oral
      antispasticity agents commonly used in Germany are baclofen, tizanidine and
      gabapentin, but physician and patient satisfaction with their effectiveness is
      low. Over the past few years, randomized controlled trials, observational studies
      and registry data have demonstrated the positive risk:benefit profile of add-on 9
      delta-tetra-hydrocannabinol:cannabidiol oromucosal spray for moderate-to-severe
      resistant MS spasticity. Herein, evidence for this novel therapeutic option is
      reviewed. A case study illustrates the level of improvement in daily functioning
      that is possible in treatment responders.

PMID- 27874497
TI  - Country breakout session highlights.
AB  - At the 2016 MS Experts Summit, country-relevant aspects pertaining to the
      management of symptoms and disability in multiple sclerosis (MS), with emphasis
      on those associated with spasticity, were explored in interactive country
      breakout sessions chaired by selected MS experts. Attendees had the opportunity
      to review and discuss topics in their own native language. After feedback from
      each session leader, key messages were collated and presented in a Plenary
      Session by Summit chair, Professor Angelo Ghezzi. Topics at this year's Summit
      included: gait tracking (Germany/Switzerland); the Care Alliance against MS
      spasticity (Italy); MS spasticity and associated symptoms (France); improvement
      in MS symptoms and functionality and patients' independence (Spain); Swedish MS
      guidelines (Sweden/Rest of World).

PMID- 27874498
TI  - What is new in multiple sclerosis spasticity research? Poster session highlights.
AB  - Each year at the MS Experts Summit, relevant research in the field of multiple
      sclerosis spasticity is featured in poster sessions. In 2016, six new studies
      were presented.

PMID- 27874499
TI  - Muscle elastography in multiple sclerosis spasticity.
AB  - Ultrasound elastography is a novel imaging modality for evaluating the elasticity
      of biological tissues. The technique is widely used in oncology to detect and
      differentiate malignant lesions in soft tissues. Studies have explored use of
      ultrasound elastography to measure the mechanical properties of muscle in
      patients with multiple sclerosis spasticity. Real-time elastography was shown to
      correlate well with subjective scales commonly used to measure MS spasticity.
      Ultrasound elastography has the potential to become a new objective gold standard
      to monitor symptom evolution in patients with MS spasticity and to evaluate the
      efficacy of antispasticity treatment.

PMID- 27874500
TI  - Rehabilitation in multiple sclerosis: the role of tele-rehabilitation/gaming.

PMID- 27874725
TI  - Impact of Perpetrator Type on Attributions of Mother Fault in Child Sexual Abuse.
AB  - Blaming nonoffending mothers for child sexual abuse has substantial negative
      consequences for both the mother and child victim. Although perpetrator type has
      been shown to influence how much blame and responsibility is placed on
      nonoffending mothers in child sexual abuse cases, research to date has focused
      primarily on perpetrators who are strangers to the child or the child's
      biological father, ignoring the effect of other father-figure perpetrators. The
      current study examined how differences in perpetrator's relationship to the
      mother impacted blame, responsibility, cause, and prevention as separate
      constructs. One hundred and eight participants from an online community sample
      were randomly assigned to read a vignette describing a child sexual abuse
      situation with a female victim and one of two perpetrators: the victim's
      biological father or the mother's boyfriend. Participants assigned significantly
      higher levels of fault for CSA to the mother when the perpetrator was the
      mother's boyfriend. Implications and future directions are discussed.

PMID- 27874726
TI  - Maternal Child Sexual Abuse Is Associated With Lower Maternal Warmth Toward
      Daughters but Not Sons.
AB  - Mothers with a history of child sexual abuse report less warmth toward their
      children, but whether this association differs by child gender is unknown. We
      examined the association of maternal child sexual abuse and warmth across child
      gender, accounting for depression, post-traumatic stress disorder, and child
      physical abuse. We verbally administered self-report measures to a cross
      sectional sample of 154 mothers with a child between 8 and 12 years old. Eighty
      five mothers based warmth responses on a son, and 69 on a daughter. We conducted
      a hierarchical multiple regression, including child gender, maternal child sexual
      abuse, child physical abuse, depression, post-traumatic stress disorder, and 4
      two-way interaction terms with child gender. Maternal depression predicted
      decreased warmth, regardless of child gender, and maternal child sexual abuse
      predicted decreased warmth, but only toward daughters. Given previous research
      suggesting that maternal warmth predicts child well-being, the current finding
      may represent an important avenue of intergenerational transmission of risk in
      girls.

PMID- 27874727
TI  - Socialization Processes and Clergy Offenders.
AB  - This article uses feminist theory to investigate how the socialization processes
      used to maintain the clergy community in the Roman Catholic Church contributes to
      a vulnerability in some clergy for sexually abusing children. This vulnerability
      is identified first in an examination of the literature on the impact of
      socialization processes on clergy offenders between the 1960s and 1980s. A
      comparison is then made with the implications of the apostolic exhortation,
      Pastores Dabo Vobis, which provides a theological basis to clergy formation. The
      article argues that the document works to ensure a continuity of socialization
      processes that not only have been shown to create a vulnerability for committing
      child sexual abuse but compound existing vulnerabilities. The article concludes
      that constraints produced by the preservation of a hegemonic masculinity and
      patriarchy retain a threat of violence against children and require recommended
      reforms.

PMID- 27874728
TI  - Child Sexual Abuse in Zimbabwe.
AB  - Although child sexual abuse is a significant public health problem globally, its
      incidence, prevention, and management is less well described in resource-poor
      settings. In poorer settings prevention initiatives assume even more importance
      since resources for managing abused children are severely limited. This article
      examines the current status of policy and practice related to the prevention of
      child sexual abuse in Zimbabwe. It identifies implementation challenges and
      highlights opportunities that could be embraced to reduce CSA in Zimbabwe, based
      on evidence synthesized from recent work. Although Zimbabwe has a well
      established legal and regulatory framework to protect children from child sexual
      abuse, implementation of existing policies is weak. Financial, human, and
      material resource constraints are frequently cited to explain limited prevention
      activity. Effective strategies for the prevention of child sexual abuse should
      focus on implementing existing legislation, targeting schoolchildren, and getting
      community involvement. A dedicated budget would help entrench these strategies,
      but gains can be achieved even in the absence of this.

PMID- 27874826
TI  - Optimization and Validation of a Fast UPLC Method for Simultaneous Determination
      of Hydroquinone, Kojic Acid, Octinoxate, Avobenzone, BHA, and BHT.
AB  - A previously published HPLC method for the simultaneous determination of six
      major components (hydroquinone, kojic acid, octinoxate, avobenzone, butylated
      hydroxyanisole, and butylated hydroxytoluene) in a skin-whitening cream was
      transferred and optimized to an ultra-performance LC system. Separation was
      achieved in a ZORBAX SB-Phenyl Rapid-Resolution High Throughput column (2.1 * 100
      mm, 1.8 MUm), using a mobile phase consisting of water with 0.1% acetic acid and
      acetonitrile at a flow rate of 0.7 mL/min. The column was maintained at 40
      degrees C, and detection was carried out at 230 nm using a diode-array detector.
      These chromatographic conditions allow the separation of the six compounds in 3
      min instead of 14 min. The extraction procedure was optimized, reducing the time
      and demonstrating its suitability. The method was validated according to
      International Conference on Harmonization guidelines, with respect to
      specificity, precision, accuracy, and linearity. Selectivity was found to be
      satisfactory. Linear regression analysis data for all compounds showed a good
      linear relationship, with r2 > 0.999 in the concentration range of 50-120% of the
      label claim for each compound. The RSD for precision and accuracy of the method
      was found to be less than 2% for all compounds. Comparison of system performance
      with the previously published HPLC method was made with respect to analysis time,
      efficacy, and resolution. The proposed method is faster and consumes less solvent
      and was applied in the determination of six major compounds in batches of skin
      whitening cream manufactured during the validation process.

PMID- 27874828
TI  - SF-1 expression in the hypothalamus is required for beneficial metabolic effects
      of exercise.
AB  - Exercise has numerous beneficial metabolic effects. The central nervous system
      (CNS) is critical for regulating energy balance and coordinating whole body
      metabolism. However, a role for the CNS in the regulation of metabolism in the
      context of the exercise remains less clear. Here, using genetically engineered
      mice we assessed the requirement of steroidogenic factor-1 (SF-1) expression in
      neurons of the ventromedial hypothalamic nucleus (VMH) in mediating the
      beneficial effects of exercise on metabolism. We found that VMH-specific deletion
      of SF-1 blunts (a) the reductions in fat mass, (b) improvements in glycemia, and
      (c) increases in energy expenditure that are associated with exercise training.
      Unexpectedly, we found that SF-1 deletion in the VMH attenuates metabolic
      responses of skeletal muscle to exercise, including induction of PGC-1alpha
      expression. Collectively, this evidence suggests that SF-1 expression in VMH
      neurons is required for the beneficial effects of exercise on metabolism.

PMID- 27874827
TI  - Weighing serological evidence of human exposure to animal influenza viruses - a
      literature review.
AB  - Assessing influenza A virus strains circulating in animals and their potential to
      cross the species barrier and cause human infections is important to improve
      human influenza surveillance and preparedness. We reviewed studies describing
      serological evidence of human exposure to animal influenza viruses. Comparing
      serological data is difficult due to a lack of standardisation in study designs
      and in laboratory methods used in published reports. Therefore, we designed a
      scoring system to assess and weigh specificity of obtained serology results in
      the selected articles. Many studies report reliable evidence of antibodies to
      swine influenza viruses among persons occupationally exposed to pigs. Most avian
      influenza studies target H5, H7 and H9 subtypes and most serological evidence of
      human exposure to avian influenza viruses is reported for these subtypes. Avian
      influenza studies receiving a low grade in this review often reported higher
      seroprevalences in humans compared with studies with a high grade. Official
      surveillance systems mainly focus on avian H5 and H7 viruses. Swine influenza
      viruses and avian subtypes other than H5 and H7 (emphasising H9) should be
      additionally included in official surveillance systems. Surveillance efforts
      should also be directed towards understudied geographical areas, such as Africa
      and South America.

PMID- 27874829
TI  - In vivo vizualisation of mono-ADP-ribosylation by dPARP16 upon amino-acid
      starvation.
AB  - PARP catalysed ADP-ribosylation is a post-translational modification involved in
      several physiological and pathological processes, including cellular stress. In
      order to visualise both Poly-, and Mono-, ADP-ribosylation in vivo, we engineered
      specific fluorescent probes. Using them, we show that amino-acid starvation
      triggers an unprecedented display of mono-ADP-ribosylation that governs the
      formation of Sec body, a recently identified stress assembly that forms in
      Drosophila cells. We show that dPARP16 catalytic activity is necessary and
      sufficient for both amino-acid starvation induced mono-ADP-ribosylation and
      subsequent Sec body formation and cell survival. Importantly, dPARP16 catalyses
      the modification of Sec16, a key Sec body component, and we show that it is a
      critical event for the formation of this stress assembly. Taken together our
      findings establish a novel example for the role of mono-ADP-ribosylation in the
      formation of stress assemblies, and link this modification to a metabolic stress.

PMID- 27874830
TI  - Cell culture-based profiling across mammals reveals DNA repair and metabolism as
      determinants of species longevity.
AB  - Mammalian lifespan differs by >100 fold, but the mechanisms associated with such
      longevity differences are not understood. Here, we conducted a study on primary
      skin fibroblasts isolated from 16 species of mammals and maintained under
      identical cell culture conditions. We developed a pipeline for obtaining species
      specific ortholog sequences, profiled gene expression by RNA-seq and small
      molecules by metabolite profiling, and identified genes and metabolites
      correlating with species longevity. Cells from longer lived species up-regulated
      genes involved in DNA repair and glucose metabolism, down-regulated proteolysis
      and protein transport, and showed high levels of amino acids but low levels of
      lysophosphatidylcholine and lysophosphatidylethanolamine. The amino acid patterns
      were recapitulated by further analyses of primate and bird fibroblasts. The study
      suggests that fibroblast profiling captures differences in longevity across
      mammals at the level of global gene expression and metabolite levels and reveals
      pathways that define these differences.

PMID- 27874831
TI  - Chronic social isolation reduces 5-HT neuronal activity via upregulated SK3
      calcium-activated potassium channels.
AB  - The activity of serotonin (5-HT) neurons is critical for mood regulation. In a
      mouse model of chronic social isolation, a known risk factor for depressive
      illness, we show that 5-HT neurons in the dorsal raphe nucleus are less
      responsive to stimulation. Probing the responsible cellular mechanisms pinpoints
      a disturbance in the expression and function of small-conductance Ca2+-activated
      K+ (SK) channels and reveals an important role for both SK2 and SK3 channels in
      normal regulation of 5-HT neuronal excitability. Chronic social isolation renders
      5-HT neurons insensitive to SK2 blockade, however inhibition of the upregulated
      SK3 channels restores normal excitability. In vivo, we demonstrate that
      inhibiting SK channels normalizes chronic social isolation-induced
      anxiety/depressive-like behaviors. Our experiments reveal a causal link for the
      first time between SK channel dysregulation and 5-HT neuron activity in a
      lifelong stress paradigm, suggesting these channels as targets for the
      development of novel therapies for mood disorders.

PMID- 27874832
TI  - Postictal behavioural impairments are due to a severe prolonged
      hypoperfusion/hypoxia event that is COX-2 dependent.
AB  - Seizures are often followed by sensory, cognitive or motor impairments during the
      postictal phase that show striking similarity to transient hypoxic/ischemic
      attacks. Here we show that seizures result in a severe hypoxic attack confined to
      the postictal period. We measured brain oxygenation in localized areas from
      freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after
      the termination of seizures. This event lasted over an hour, is mediated by
      hypoperfusion, generalizes to people with epilepsy, and is attenuated by
      inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these
      targets we separated the seizure from the resulting severe hypoxia and show that
      structure specific postictal memory and behavioral impairments are the
      consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much
      more than a disease hallmarked by seizures, since the occurrence of postictal
      hypoperfusion/hypoxia results in a separate set of neurological consequences that
      are currently not being treated and are preventable.

PMID- 27874833
TI  - A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release
      of HDAC mediated repression.
AB  - Natural Killer (NK) cells are essential for control of viral infection and
      cancer. NK cells express NKG2D, an activating receptor that directly recognizes
      NKG2D ligands. These are expressed at low level on healthy cells, but are induced
      by stresses like infection and transformation. The physiological events that
      drive NKG2D ligand expression during infection are still poorly understood. We
      observed that the mouse cytomegalovirus encoded protein m18 is necessary and
      sufficient to drive expression of the RAE-1 family of NKG2D ligands. We
      demonstrate that RAE-1 is transcriptionally repressed by histone deacetylase
      inhibitor 3 (HDAC3) in healthy cells, and m18 relieves this repression by
      directly interacting with Casein Kinase II and preventing it from activating
      HDAC3. Accordingly, we found that HDAC inhibiting proteins from human
      herpesviruses induce human NKG2D ligand ULBP-1. Thus our findings indicate that
      virally mediated HDAC inhibition can act as a signal for the host to activate NK
      cell recognition.

PMID- 27874834
TI  - Recovery of erectile function comparing autologous nerve grafts, unseeded
      conduits, Schwann-cell-seeded guidance tubes and GDNF-overexpressing Schwann cell
      grafts.
AB  - Dissection of the cavernous nerves during radical prostatectomy for prostate
      cancer eliminates spontaneous erections. Using the rat as an experimental model,
      we compared the regenerative capacity of autologous nerve grafts and Schwann-cell
      seeded nerve guides. After bilateral excision of cavernous nerve segments,
      cavernous nerves were reconstructed using unseeded silicon tubes, nerve
      autografts and silicon tubes seeded with either Glial-cell-line-derived (GDNF)
      overexpressing or green fluorescent protein (GFP)-expressing Schwann cells (SCs)
      (16 study nerves per group). Control groups underwent either a sham operation or
      bilateral excision of cavernous nerve segments without repair. After 12 weeks
      erectile function was assessed by neurostimulation and intracavernous pressure
      (ICP) measurement. The reconstructed nerve segments were excised and
      histologically analyzed. We demonstrated an intact erectile response upon
      neurostimulation in 25% (4/16) of autologous nerve grafts, in 50% (8/16) of
      unseeded tubes, in 75% (12/16) of the Schwann-cell-GFP group and in 93.75%
      (15/16) of the GDNF group. ICP was significantly increased when comparing the
      Schwann-cell-GFP group with nerve autografts, unseeded conduits and negative
      controls (P<0.005). In conclusion, Schwann-cell-seeded scaffolds combined with
      neurotrophic factors are superior to unseeded tubes and autologous nerve grafts.
      They present a promising therapeutic approach for the repair of erectile nerve
      gaps.

PMID- 27874835
TI  - Heterotypic mouse models of canine osteosarcoma recapitulate tumor heterogeneity
      and biological behavior.
AB  - Osteosarcoma (OS) is a heterogeneous and rare disease with a disproportionate
      impact because it mainly affects children and adolescents. Lamentably, more than
      half of patients with OS succumb to metastatic disease. Clarification of the
      etiology of the disease, development of better strategies to manage progression,
      and methods to guide personalized treatments are among the unmet health needs for
      OS patients. Progress in managing the disease has been hindered by the extreme
      heterogeneity of OS; thus, better models that accurately recapitulate the natural
      heterogeneity of the disease are needed. For this study, we used cell lines
      derived from two spontaneous canine OS tumors with distinctly different
      biological behavior (OS-1 and OS-2) for heterotypic in vivo modeling that
      recapitulates the heterogeneous biology and behavior of this disease. Both cell
      lines demonstrated stability of the transcriptome when grown as orthotopic
      xenografts in athymic nude mice. Consistent with the behavior of the original
      tumors, OS-2 xenografts grew more rapidly at the primary site and had greater
      propensity to disseminate to lung and establish microscopic metastasis. Moreover,
      OS-2 promoted formation of a different tumor-associated stromal environment than
      OS-1 xenografts. OS-2-derived tumors comprised a larger percentage of the
      xenograft tumors than OS-1-derived tumors. In addition, a robust pro-inflammatory
      population dominated the stromal cell infiltrates in OS-2 xenografts, whereas a
      mesenchymal population with a gene signature reflecting myogenic signaling
      dominated those in the OS-1 xenografts. Our studies show that canine OS cell
      lines maintain intrinsic features of the tumors from which they were derived and
      recapitulate the heterogeneous biology and behavior of bone cancer in mouse
      models. This system provides a resource to understand essential interactions
      between tumor cells and the stromal environment that drive the progression and
      metastatic propensity of OS.

PMID- 27874837
TI  - Effectiveness of Spiritist Passe (Spiritual Healing) on the Psychophysiological
      Parameters in Hospitalized Patients.
AB  - Context * The coexistence of affective disorders, especially anxiety and
      depression, with medical illness is a topic of considerable clinical and research
      interest. Complementary biofield modalities are therapies that involve touch or
      placement of the hands in or through biofields. Spiritual healing, or Spiritist
      passe (SP), is a kind of laying on of hands (LOH), and therefore is a biofield
      therapy. Objective * The current study intended to evaluate the effects of SP on
      psychological parameters such as anxiety and depression and on the perceptions of
      muscle tension and wellness as well as physiological parameters, such as pain
      intensity, heart rate (HR), and oxygen saturation (SpO2). Design * This study was
      a randomized, controlled trial. Setting * The study took place at the medical
      clinic of the clinical hospital of the Federal University of Triangulo Mineiro
      (HC/UFTM) in Uberaba, Brazil. Participants * The participants were patients aged
      >=18 y who had been hospitalized in the clinic between August 2014 and June 2015.
      Intervention * Participants in the no-SP and SP groups were instructed to direct
      their thoughts to Jesus with wishes to heal during the intervention. In the SP
      group, the patients underwent application of the SP, and in the no-SP group,
      workers, students, or volunteers at the Clinical Hospital of Uberaba practiced a
      kind of LOH in a nonspiritual therapy with intention to healing emitting sincere
      wishes of improvement to the patients by thought. All procedures in those groups
      were carried out during a 10-min period on 3 consecutive days. In the control
      group, the patients lay for 10 min during the same periods on the 3 days, with no
      intervention occurring. Outcome Measures * The study evaluated depression and
      anxiety using the Hospital Anxiety and Depression (HAD) scale as well as
      patients' pain using a visual analog scale (VAS). The study also measured their
      perceptions of muscle tension and wellness and their physiological parameters: HR
      and SpO2. Results * Seventy-two patients consented to participate in the study.
      The SP group showed statistically significant reductions in anxiety (P < .001)
      and depression (P = .008) between baseline and postintervention, with perceptions
      of muscle tension significantly decreasing on day 1 (D1) and day 3 (D3) of the
      study (both < .001) after the interventions and wellness significantly increasing
      between baseline and postintervention (P = .001) and when compared with the
      control and no-SP groups, with P = .001. The SP group presented the smallest
      numbers for HR after the interventions, but no significant differences were found
      between groups for HR, SpO2, and pain on the VAS. Conclusions * The current
      research team has concluded that the SP was effective in promoting a state of
      muscle relaxation, reducing anxiety and depression, decreasing muscle tension,
      and, consequently, raising the perceptions of wellness in hospitalized patients.

PMID- 27874836
TI  - Whole-genome sequence, SNP chips and pedigree structure: building demographic
      profiles in domestic dog breeds to optimize genetic-trait mapping.
AB  - In the decade following publication of the draft genome sequence of the domestic
      dog, extraordinary advances with application to several fields have been credited
      to the canine genetic system. Taking advantage of closed breeding populations and
      the subsequent selection for aesthetic and behavioral characteristics,
      researchers have leveraged the dog as an effective natural model for the study of
      complex traits, such as disease susceptibility, behavior and morphology,
      generating unique contributions to human health and biology. When designing
      genetic studies using purebred dogs, it is essential to consider the unique
      demography of each population, including estimation of effective population size
      and timing of population bottlenecks. The analytical design approach for genome
      wide association studies (GWAS) and analysis of whole-genome sequence (WGS)
      experiments are inextricable from demographic data. We have performed a
      comprehensive study of genomic homozygosity, using high-depth WGS data for 90
      individuals, and Illumina HD SNP data from 800 individuals representing 80
      breeds. These data were coupled with extensive pedigree data analyses for 11
      breeds that, together, allowed us to compute breed structure, demography, and
      molecular measures of genome diversity. Our comparative analyses characterize the
      extent, formation and implication of breed-specific diversity as it relates to
      population structure. These data demonstrate the relationship between breed
      specific genome dynamics and population architecture, and provide important
      considerations influencing the technological and cohort design of association and
      other genomic studies.

PMID- 27874839
TI  - Online access and motivation of tutors of health professions higher education.
AB  - The case study of PUNTOZERO as an open web lab for activities, research and
      support to 5 Master's courses for the health professions is described. A virtual
      learning environment integrated in a much wider network including social networks
      and open resources was experimented on for five Master's Courses for the health
      professions at the University of Parma. A social learning approach might be
      applied by the engagement of motivated and skilled tutors. This is not only
      needed for the improvement and integration of the digital and collaborative
      dimension in higher education, but it aims to introduce issues and biases of
      emerging e-health and online networking dimensions for future healthcare
      professionals. Elements of e-readiness to train tutors and improve their digital
      skills and e-moderation approaches are evident. This emerged during an online and
      asynchronous interview with two tutors out of the four that were involved, by the
      use of a wiki where interviewer and informants could both read and add contents
      and comments.

PMID- 27874838
TI  - Associations of Cardiovascular Risk Factors with Carotid Intima-Media Thickness
      in Middle-Age Adults and Elders.
AB  - AIMS: Elevated carotid intima-media thickness (cIMT) is a preclinical phenotype
      of atherosclerotic diseases. There are significant sex differences in the
      morbidities of cardiovascular diseases and their major determinants, and we
      explored the sex-specific effects of cardiovascular factors on cIMT by a
      community-based study. METHODS: We measured the cIMT and cardiovascular profiles
      of 1579 residents aged 40-74 years in northern Taiwan. Multivariate regression
      analyses were used to assess the effects and contributions of these factors on
      cIMT. RESULTS: Males had significantly higher mean (+/-SD) of cIMT than females
      (0.668+/-0.113 vs. 0.632+/- 0.100 nm, p<0.0001). The common factors of the best
      fit regression models in both sexes were age, BMI, and LDL-/HDL-C ratio; however,
      their contributions and effects were different. The partial coefficients of
      determination (r2) were 17.9, 5.8, and 4.1%, respectively, for males and were
      27.8, 1.4, and 1.2%, respectively, for females. Test statistics showed that the
      regression coefficients of BMI and LDL-/HDL-C ratio of males were significantly
      higher than those of females. As compared with females, per 1.0 SD increases of
      BMI and LDL-/HDL-C in males resulted in 0.0971 (p=0.030) and 0.1177 (p=0.0087),
      respectively, SD increases in cIMT. There was no difference in the means of cIMT
      between pre- and post-menopausal women of the same age groups. CONCLUSIONS: There
      was a significant sex difference in cIMT. The contributions and effects of LDL
      /HDL-C ratio and BMI on cIMT were more profound in males. Our findings indicate
      that sex-specific factors, but possibly not menstrual status-related factors,
      contribute to thicker cIMT.

PMID- 27874840
TI  - An integrated narrative nursing model: towards a new healthcare paradigm.
AB  - In the traditional biomedical model of clinical practice, which assumes a
      medicine focused on disease, diseases are considered as biological or psycho
      physiological universal entities. This explanation, although necessary, is not
      enough. Several authors have recently become interested in the use of narrative
      practices in the medical care setting, underlining the increasing importance of
      "a patient-centered approach", a "relationship -centered care" and "narrative
      medicine". Even in Nursing, the challenge was to combine two models that seemed
      incompatible: the Evidence-Based Nursing Model and the Narrative-Based Nursing
      Model. The first one is based on the disease and is capable of reaching
      measurable objectives. It is marked by rationality, objectivity, determinism,
      unilateralism and linearity, and its methods emphasize logic, control,
      measurement and deduction. The second model is based on a global approach,
      resulting in a psycho-social perspective which stresses the importance of
      individuality, interpersonal relationship, and the illness and sickness as
      significant parts of healthcare. Through a short examination of different
      narrative models in medicine, we underlined some principles which can be used in
      nursing practice and we suggested a new healthcare paradigm based on integrated
      narrative nursing. It represents a groundbreaking new normative approach,
      deriving from different epistemological (positivist paradigm and interpretive
      paradigm) and methodological approaches that integrate quantitative data already
      normally detected on the patient, with subjective information obtained from the
      person and his family, and by the social impact that the disease causes. The
      integrated narrative nursing makes use of quantitative (e.g. scales and
      scientific evidence) and qualitative tools (e.g. narratives, autobiographies,
      therapeutic emplotment and patient's agenda). This approach, based on holistic
      comprehension, hermeneutic dialogue and a high degree of narrative skill,
      produces different ways of understanding and offering cure, care and assistance.
      This could allow a targeted assessment, a precise diagnosis and a personalized
      education. The benefits coming from the use of this paradigm are several, as for
      example, to disseminate a personal experience in a perspective of humanization,
      to improves quality of life and to create a positive effects on patient care
      outcomes.

PMID- 27874841
TI  - Using the Theory of Planned Behavior to explore hospital-based nurses' intention
      to use peripherally inserted central catheter (PICC): a survey study.
AB  - BACKGROUND AND AIM OF THE WORK: The peripherally inserted central catheters
      (PICC) have become an alternative to the traditional CVC. PICCs are usually
      inserted by trained nurses who decided to attend and complete a special training
      on PICC insertion and management. The present work aimed to investigate the
      intention of using PICC in a sample of hospital-based nurses using the theory of
      planned behavior as theoretical framework. METHODS: A cross-sectional design was
      used in which a questionnaire was delivered to 199 nurses. RESULTS: According to
      the theory of planned behavior, the attitude toward the use of PICC, subjective
      norms and perceived self-efficacy predicted the intention to use PICC. Contrary
      to the expectations, the effect of subjective norms on intention to use PICC was
      mediated by attitude and self-efficacy. Finally, age of participants was
      negatively related to the intention to use the PICC. CONCLUSIONS: The theory of
      planned behavior offers a useful framework to explain nurses' intention to use
      PICC. Shared norms favoring the use of PICC seem to increase both nurse's
      positive attitudes and self-efficacy whit respect to the use of these devices.
      Thus, it appears that to train professionals individually does not necessarily
      results in an increased use of PICC.

PMID- 27874842
TI  - Efficacy of video-music therapy on quality of life improvement in a group of
      patients with Alzheimer's disease: a pre-post study.
AB  - BACKGROUND AND AIM OF THE STUDY: Alzheimer's disease is the most common
      degenerative dementia with a predominantly senile onset. The difficult management
      of altered behaviour related to this disorder, poorly responsive to
      pharmacological treatments, has stimulated growth in non-pharmacological
      interventions, such as music therapy, whose effectiveness has not been supported
      by the literature up to now. The aim of this study was to evaluate the efficacy
      of video-music therapy on quality of life improvement in Patients affected by
      Alzheimer's Disease (AD). METHODS: A pre-post study was conducted in a
      residential facility. 32 AD Patients, who attended this facility daily to
      participate in supportive and rehabilitative programs, were treated with 2 cycles
      of 6 video-music-therapy sessions, which consisted of folk music and video,
      recalling local traditions. In order to investigate their cognitive status, Mini
      Mental State Examination (MMSE) was administered and Patients were divided into
      stages according to MMSE scores. After each session of video-music-therapy,
      Quality of Life in Alzheimer's Disease Scale (QOL-AD) was administered to our
      Patients. RESULTS: 21 AD Patients completed the 2 cycles of video-music therapy.
      Among them, only the Patients with questionable, mild and moderate neurocognitive
      impairment (MMSE Stages 1, 2, 3) reported an improvement in their quality of
      life, whereas the Patients with severe deterioration (MMSE stage 4) did not
      report any change. Many items of QOL-AD improved, showing a statistically
      significantly correlation to each other. CONCLUSIONS: Video-music therapy was a
      valuable tool for improving the quality of life only in Patients affected by less
      severe neurocognitive impairment.

PMID- 27874843
TI  - High Fidelity Simulation Experience in Emergency settings: doctors and nurses
      satisfaction levels.
AB  - BACKGROUND AND AIM OF THE WORK: Lots of studies describe High Fidelity Simulation
      (HFS) as an experience well-accepted by the learners. This study has explored
      doctors and nurses satisfaction levels during HFS sessions, searching the
      associations with the setting of simulation events (simulation center or on the
      field simulation). Moreover, we studied the correlation between HFS experience
      satisfaction levels and the socio-demographic features of the participants.
      METHODS: Mixed method study, using the Satisfaction of High-Fidelity Simulation
      Experience (SESAF) questionnaire through an online survey. SESAF was administered
      to doctors and nurses who previously took part to HFS sessions in a simulation
      center or in the field. Quantitative data were analyzed through descriptive and
      inferential statistics methods; qualitative data was performed through the Giorgi
      method. RESULTS: 143 doctors and 94 nurses filled the questionnaire. The
      satisfaction level was high: on a 10 points scale, the mean score was 8.17 (SD+/
      1.924). There was no significant difference between doctors and nurses
      satisfaction levels in almost all the SESAF factors. We didn't find any
      correlation between gender and HFS experience satisfaction levels. The knowledge
      of theoretical aspects of the simulated case before the HFS experience is related
      to a higher general satisfaction (r=0.166 p=0.05), a higher effectiveness of
      debriefing (r=0,143 p=0,05), and a higher professional impact (r=0.143 p=0.05).
      The respondents that performed a HFS on the field, were more satisfied than the
      others, and experienced a higher "professional impact", "clinical reasoning and
      self efficacy", and "team dynamics" (p< 0,01). Narrative data suggest that HFS
      facilitators should improve their behaviors during the debriefing. CONCLUSIONS:
      Healthcare managers should extend the HFS to all kind of healthcare workers in
      real clinical settings. There is the need to improve and implement the
      communication competences of HFS facilitators.

PMID- 27874844
TI  - Making visible the invisible and vice versa. Bodies and organisational
      arrangements in the Intensive Care Unit.
AB  - BACKGROUND AND AIMS: The effectiveness of the treatments carried out in the
      Intensive Care Unit (ICU) is guaranteed by a socio-technical ensemble where
      material resources, scientific knowledge, technological artefacts, social norms,
      spatial dispositions, and professional practices coexist and constantly interact.
      This paper intends to penetrate such an ensemble for analysing the moral order
      produced and maintained in everyday medical practice. METHOD: The results of a
      case study, carried out in the ICU of a hospital in the north of Italy between
      2006 and 2007 are reported. The study was performed using ethnographic methods:
      participant observation, ethnographic interviews, and semi-structured interviews.
      RESULTS: I illustrate how ward organisation and professional practices of medical
      and nurse staff create and reproduce two dispositions of body centred on the
      staff's perception of the therapeutic appropriateness of patients. On one side,
      there are the bodies that staff expect to get better, and these bodies are
      exposed through a series of organisational devices and activities in order to
      make them immediately accessible and available for every type of treatment; on
      the other side, the bodies of chronic and terminal patients tend to become
      invisibles in the working practice of the unit. This process does not follow any
      guideline or protocol but is embodied in informal routine and communicative
      interactions. CONCLUSIONS: The invisibility surrounding certain patients can be
      seen as strategies for the management of professional conflict and bioethical
      issues that stem from different interpretations of the degree of severity of the
      patients' conditions.

PMID- 27874845
TI  - Collaboration and emotions to the test: the experience of FILe volunteers in
      hospices.
AB  - BACKGROUND AND AIMS: This study seeks to provide an in-depth analysis of care
      based interaction in the experiences of volunteers working in lenitherapy (pain
      therapy) through the case study of hospices in Florence, Italy. METHOD: A
      qualitative method of data collection was chosen: the field research made use of
      open-ended questionnaires distributed to trained but unspecialised volunteers (V
      = 32) and to volunteers with hospital-based medical expertise (PV = 35) acting
      for the Italian Lenitherapy Foundation (FILe) and operating in hospices within
      the ex-ASL (Local Health Unit) of Florence. RESULTS: By analysing the 67
      questionnaires collected, it has been possible to reconstruct and interpret the
      interactional dynamics that exist between the various figures present within a
      hospice, bringing into focus the most salient aspects of both the organisational
      context and emotional setting. CONCLUSIONS: The research experience, by
      highlighting everyday unseen aspects that are inaccessible to an 'internal' eye,
      has made it possible to better characterise the dynamics of unsuccessful
      collaboration between team members and potential areas of conflict. Finally,
      where these dynamics have been observed, an attempt has been made to outline
      priorities for change and possible directions to be taken, so as to promote
      defusing actions and restore synergy and fluidity to the FILe system.

PMID- 27874846
TI  - Communications and relationships between patient and nurse in Intensive Care
      Unit: knowledge, knowledge of the work, knowledge of the emotional state.
AB  - BACKGROUND AND AIM: In an Intensive Care Unit (ICU) the communication between
      nurse and patient, the core of the care, is often hindered by patient's cognitive
      alterations and critical situation, by devices employed for the mechanical
      ventilation, and by the clinical and care-giving setting. How to overcome these
      barriers? How is the relational and communicative approach between nurse and
      patient unable to express him or herself to be managed? The available literature
      reveals that studies on communication with difficult patients, such as those
      treated in ICU are currently scarce. METHOD: The present research offers a
      contribution in this respect, through fact-finding about the knowledge acquired
      by professional studies or work experiences, the personal and institutional
      techniques implemented in regards to communication (knowledge of the work), the
      relational behaviours and the emotional experience with patients (knowledge of
      the emotional state) of nurses working in the Intensive Care Units. A semi
      structured interview have been designed and submitted to 30 nurses working in
      fourteen Highly Specialized Centres (HUB) in Emilia Romagna, Italy. Two nurses
      with different years of experience in the field have been chosen for each
      Operating Unit. RESULTS: According to the interviewees paraverbal communication
      is the most common way to communicate with patients: different strategies are
      employed such as facial expression or lip movement. In any case, the nurse has
      the task to choose the most suitable technique according to his or her
      experiences, his or her knowledge and the patient him or herself. The results
      claim that lack of specific training on communicative aspects of care, should be
      combined with an attitude of being prone to listening to and understanding the
      needs of the patient and of his or her family as well. CONCLUSION: The
      interviewees declare they have a solid preparation in the bio-clinical aspect of
      care, but both new hired nurses and experts affirm that they need a specific
      training in relational and communicative aspects, proving its importance.

PMID- 27874847
TI  - Early changes in emotional processing as a marker of clinical response to SSRI
      treatment in depression.
AB  - Antidepressant treatment reduces behavioural and neural markers of negative
      emotional bias early in treatment and has been proposed as a mechanism of
      antidepressant drug action. Here, we provide a critical test of this hypothesis
      by assessing whether neural markers of early emotional processing changes predict
      later clinical response in depression. Thirty-five unmedicated patients with
      major depression took the selective serotonin re-uptake inhibitor (SSRI),
      escitalopram (10 mg), over 6 weeks, and were classified as responders (22
      patients) versus non-responders (13 patients), based on at least a 50% reduction
      in symptoms by the end of treatment. The neural response to fearful and happy
      emotional facial expressions was assessed before and after 7 days of treatment
      using functional magnetic resonance imaging. Changes in the neural response to
      these facial cues after 7 days of escitalopram were compared in patients as a
      function of later clinical response. A sample of healthy controls was also
      assessed. At baseline, depressed patients showed greater activation to fear
      versus happy faces than controls in the insula and dorsal anterior cingulate.
      Depressed patients who went on to respond to the SSRI had a greater reduction in
      neural activity to fearful versus happy facial expressions after just 7 days of
      escitalopram across a network of regions including the anterior cingulate,
      insula, amygdala and thalamus. Mediation analysis confirmed that the direct
      effect of neural change on symptom response was not mediated by initial changes
      in depressive symptoms. These results support the hypothesis that early changes
      in emotional processing with antidepressant treatment are the basis of later
      clinical improvement. As such, early correction of negative bias may be a key
      mechanism of antidepressant drug action and a potentially useful predictor of
      therapeutic response.

PMID- 27874849
TI  - Systematic chemical-genetic and chemical-chemical interaction datasets for
      prediction of compound synergism.
AB  - The network structure of biological systems suggests that effective therapeutic
      intervention may require combinations of agents that act synergistically.
      However, a dearth of systematic chemical combination datasets have limited the
      development of predictive algorithms for chemical synergism. Here, we report two
      large datasets of linked chemical-genetic and chemical-chemical interactions in
      the budding yeast Saccharomyces cerevisiae. We screened 5,518 unique compounds
      against 242 diverse yeast gene deletion strains to generate an extended chemical
      genetic matrix (CGM) of 492,126 chemical-gene interaction measurements. This CGM
      dataset contained 1,434 genotype-specific inhibitors, termed cryptagens. We
      selected 128 structurally diverse cryptagens and tested all pairwise combinations
      to generate a benchmark dataset of 8,128 pairwise chemical-chemical interaction
      tests for synergy prediction, termed the cryptagen matrix (CM). An accompanying
      database resource called ChemGRID was developed to enable analysis, visualisation
      and downloads of all data. The CGM and CM datasets will facilitate the
      benchmarking of computational approaches for synergy prediction, as well as
      chemical structure-activity relationship models for anti-fungal drug discovery.

PMID- 27874851
TI  - Reduced dynamical maps in the presence of initial correlations.
AB  - We introduce a framework for the construction of completely positive dynamical
      evolutions in the presence of system-environment initial correlations. The
      construction relies upon commutativity of the compatibility domain obtained by
      considering the marginals with respect to the environmental degrees of freedom of
      the considered class of correlated states, as well as basic properties of
      completely positive maps. Our approach allows to consider states that can have
      finite discord, though it does not include entangled states, and it explicitly
      shows the non-uniqueness of the completely positive extensions of the obtained
      dynamical map outside the compatibility domain. The possible relevance of such
      maps for the treatment of open quantum system dynamics is critically discussed,
      together with the connection to previous literature.

PMID- 27874848
TI  - The human BDNF gene: peripheral gene expression and protein levels as biomarkers
      for psychiatric disorders.
AB  - Brain-derived neurotrophic factor (BDNF) regulates the survival and growth of
      neurons, and influences synaptic efficiency and plasticity. The human BDNF gene
      consists of 11 exons, and distinct BDNF transcripts are produced through the use
      of alternative promoters and splicing events. The majority of the BDNF
      transcripts can be detected not only in the brain but also in the blood cells,
      although no study has yet investigated the differential expression of BDNF
      transcripts at the peripheral level. This review provides a description of the
      human BDNF gene structure as well as a summary of clinical and preclinical
      evidence supporting the role of BDNF in the pathogenesis of psychiatric
      disorders. We will discuss several mechanisms as possibly underlying BDNF
      modulation, including epigenetic mechanisms. We will also discuss the potential
      use of peripheral BDNF as a biomarker for psychiatric disorders, focusing on the
      factors that can influence BDNF gene expression and protein levels. Within this
      context, we have also characterized, for we believe the first time, the
      expression of BDNF transcripts in the blood, with the aim to provide novel
      insights into the molecular mechanisms and signaling that may regulate peripheral
      BDNF gene expression levels.

PMID- 27874852
TI  - A global gas flaring black carbon emission rate dataset from 1994 to 2012.
AB  - Global flaring of associated petroleum gas is a potential emission source of
      particulate matters (PM) and could be notable in some specific regions that are
      in urgent need of mitigation. PM emitted from gas flaring is mainly in the form
      of black carbon (BC), which is a strong short-lived climate forcer. However, BC
      from gas flaring has been neglected in most global/regional emission inventories
      and is rarely considered in climate modeling. Here we present a global gas
      flaring BC emission rate dataset for the period 1994-2012 in a machine-readable
      format. We develop a region-dependent gas flaring BC emission factor database
      based on the chemical compositions of associated petroleum gas at various oil
      fields. Gas flaring BC emission rates are estimated using this emission factor
      database and flaring volumes retrieved from satellite imagery. Evaluation using a
      chemical transport model suggests that consideration of gas flaring emissions can
      improve model performance. This dataset will benefit and inform a broad range of
      research topics, e.g., carbon budget, air quality/climate modeling, and
      environmental/human exposure.

PMID- 27874850
TI  - A microarray whole-genome gene expression dataset in a rat model of inflammatory
      corneal angiogenesis.
AB  - In angiogenesis with concurrent inflammation, many pathways are activated, some
      linked to VEGF and others largely VEGF-independent. Pathways involving
      inflammatory mediators, chemokines, and micro-RNAs may play important roles in
      maintaining a pro-angiogenic environment or mediating angiogenic regression.
      Here, we describe a gene expression dataset to facilitate exploration of pro
      angiogenic, pro-inflammatory, and remodelling/normalization-associated genes
      during both an active capillary sprouting phase, and in the restoration of an
      avascular phenotype. The dataset was generated by microarray analysis of the
      whole transcriptome in a rat model of suture-induced inflammatory corneal
      neovascularisation. Regions of active capillary sprout growth or regression in
      the cornea were harvested and total RNA extracted from four biological replicates
      per group. High quality RNA was obtained for gene expression analysis using
      microarrays. Fold change of selected genes was validated by qPCR, and protein
      expression was evaluated by immunohistochemistry. We provide a gene expression
      dataset that may be re-used to investigate corneal neovascularisation, and may
      also have implications in other contexts of inflammation-mediated angiogenesis.

PMID- 27874853
TI  - Introduction of neutralizing immunogenicity index to the rational design of MERS
      coronavirus subunit vaccines.
AB  - Viral subunit vaccines often contain immunodominant non-neutralizing epitopes
      that divert host immune responses. These epitopes should be eliminated in vaccine
      design, but there is no reliable method for evaluating an epitope's capacity to
      elicit neutralizing immune responses. Here we introduce a new concept
      'neutralizing immunogenicity index' (NII) to evaluate an epitope's neutralizing
      immunogenicity. To determine the NII, we mask the epitope with a glycan probe and
      then assess the epitope's contribution to the vaccine's overall neutralizing
      immunogenicity. As proof-of-concept, we measure the NII for different epitopes on
      an immunogen comprised of the receptor-binding domain from MERS coronavirus (MERS
      CoV). Further, we design a variant form of this vaccine by masking an epitope
      that has a negative NII score. This engineered vaccine demonstrates significantly
      enhanced efficacy in protecting transgenic mice from lethal MERS-CoV challenge.
      Our study may guide the rational design of highly effective subunit vaccines to
      combat MERS-CoV and other life-threatening viruses.

PMID- 27874854
TI  - Graphene materials as 2D non-viral gene transfer vector platforms.
AB  - Advances in genomics and gene therapy could offer solutions to many diseases that
      remain incurable today, however, one of the critical reasons halting clinical
      progress is due to the difficulty in designing efficient and safe delivery
      vectors for the appropriate genetic cargo. Safety and large-scale production
      concerns counter-balance the high gene transfer efficiency achieved with viral
      vectors, while non-viral strategies have yet to become sufficiently efficient.
      The extraordinary physicochemical, optical and photothermal properties of
      graphene-based materials (GBMs) could offer two-dimensional components for the
      design of nucleic acid carrier systems. We discuss here such properties and their
      implications for the optimization of gene delivery. While the design of such
      vectors is still in its infancy, we provide here an exhaustive and up-to-date
      analysis of the studies that have explored GBMs as gene transfer vectors,
      focusing on the functionalization strategies followed to improve vector
      performance and on the biological effects attained.

PMID- 27874855
TI  - Conditional control of suicide gene expression in tumor cells with theophylline
      responsive ribozyme.
AB  - Numerous synthetic RNA-based controls for integrating sensing switches with
      function devices have been demonstrated in a variety of organisms for gene
      regulation. Although potential advantages of RNA-based genetic control strategies
      have been shown in clinical applications, successfully extending these engineered
      systems into medical applications has seldom been reported. Here, a synthetic RNA
      based ribozyme system and its application in advancing rationally designed
      cellular therapy were described. The theophylline-responsive, ribozyme-based
      device provided a powerful platform for suicide gene expression regulation in
      tumor cells. Moreover, we demonstrate the ability of our synthetic controller to
      modulate effectively the viability of the cells in response to drug input. Our
      RNA-based regulatory system could dose-dependently fine-tune transgene expression
      in mammalian cells and address urgent limitations in existing genetic control
      strategies for gene- and cell-based therapies in the future.

PMID- 27874856
TI  - In vivo Editing of the Human Mutant Rhodopsin Gene by Electroporation of Plasmid
      based CRISPR/Cas9 in the Mouse Retina.
AB  - The bacterial CRISPR/Cas system has proven to be an efficient tool for genetic
      manipulation in various organisms. Here we show the application of CRISPR-Cas9
      technology to edit the human Rhodopsin (RHO) gene in a mouse model for autosomal
      dominant Retinitis Pigmentosa. We designed single or double sgRNAs to knock-down
      mutant RHO expression by targeting exon 1 of the RHO gene carrying the P23H
      dominant mutation. By delivering Cas9 and sgRNAs in a single plasmid we induced
      an efficient gene editing in vitro, in HeLa cells engineered to constitutively
      express the P23H mutant RHO allele. Similarly, after subretinal electroporation
      of the CRISPR/Cas9 plasmid expressing two sgRNAs into P23H RHO transgenic mice,
      we scored specific gene editing as well as significant reduction of the mutant
      RHO protein. Successful in vivo application of the CRISPR/Cas9 system confirms
      its efficacy as a genetic engineering tool in photoreceptor cells.

PMID- 27874857
TI  - Antisense Oligonucleotide Mediated Splice Correction of a Deep Intronic Mutation
      in OPA1.
AB  - Inherited optic neuropathies (ION) present an important cause of blindness in the
      European working-age population. Recently we reported the discovery of four
      independent families with deep intronic mutations in the main inherited optic
      neuropathies gene OPA1. These deep intronic mutations cause mis-splicing of the
      OPA1 pre-messenger-RNA transcripts by creating cryptic acceptor splice sites. As
      a rescue strategy we sought to prevent mis-splicing of the mutant pre-messenger
      RNA by applying 2'O-methyl-antisense oligonucleotides (AONs) with a full-length
      phosphorothioate backbone that target the cryptic acceptor splice sites and the
      predicted novel branch point created by the deep intronic mutations,
      respectively. Transfection of patient-derived primary fibroblasts with these AONs
      induced correct splicing of the mutant pre-messenger-RNA in a time and
      concentration dependent mode of action, as detected by pyrosequencing of
      informative heterozygous variants. The treatment showed strong rescue effects
      (~55%) using the cryptic acceptor splice sites targeting AON and moderate rescue
      (~16%) using the branch point targeting AON. The highest efficacy of Splice
      correction could be observed 4 days after treatment however, significant effects
      were still seen 14 days post-transfection. Western blot analysis revealed
      increased amounts of OPA1 protein with maximum amounts at ~3 days post-treatment.
      In summary, we provide the first mutation-specific in vitro rescue strategy for
      OPA1 deficiency using synthetic AONs.

PMID- 27874858
TI  - Prompt gravity signal induced by the 2011 Tohoku-Oki earthquake.
AB  - Transient gravity changes are expected to occur at all distances during an
      earthquake rupture, even before the arrival of seismic waves. Here we report on
      the search of such a prompt gravity signal in data recorded by a superconducting
      gravimeter and broadband seismometers during the 2011 Mw 9.0 Tohoku-Oki
      earthquake. During the earthquake rupture, a signal exceeding the background
      noise is observed with a statistical significance higher than 99% and an
      amplitude of a fraction of MUGal, consistent in sign and order of magnitude with
      theoretical predictions from a first-order model. While prompt gravity signal
      detection with state-of-the-art gravimeters and seismometers is challenged by
      background seismic noise, its robust detection with gravity gradiometers under
      development could open new directions in earthquake seismology, and overcome
      fundamental limitations of current earthquake early-warning systems imposed by
      the propagation speed of seismic waves.

PMID- 27874859
TI  - A single heterochronic blood exchange reveals rapid inhibition of multiple
      tissues by old blood.
AB  - Heterochronic parabiosis rejuvenates the performance of old tissue stem cells at
      some expense to the young, but whether this is through shared circulation or
      shared organs is unclear. Here we show that heterochronic blood exchange between
      young and old mice without sharing other organs, affects tissues within a few
      days, and leads to different outcomes than heterochronic parabiosis.
      Investigating muscle, liver and brain hippocampus, in the presence or absence of
      muscle injury, we find that, in many cases, the inhibitory effects of old blood
      are more pronounced than the benefits of young, and that peripheral tissue injury
      compounds the negative effects. We also explore mechanistic explanations,
      including the role of B2M and TGF-beta. We conclude that, compared with
      heterochronic parabiosis, heterochronic blood exchange in small animals is less
      invasive and enables better-controlled studies with more immediate translation to
      therapies for humans.

PMID- 27874860
TI  - Targeted drug delivery through the traceless release of tertiary and heteroaryl
      amines from antibody-drug conjugates.
AB  - The reversible attachment of a small-molecule drug to a carrier for targeted
      delivery can improve pharmacokinetics and the therapeutic index. Previous studies
      have reported the delivery of molecules that contain primary and secondary amines
      via an amide or carbamate bond; however, the ability to employ tertiary-amine
      containing bioactive molecules has been elusive. Here we describe a bioreversible
      linkage based on a quaternary ammonium that can be used to connect a broad array
      of tertiary and heteroaryl amines to a carrier protein. Using a concise,
      protecting-group-free synthesis we demonstrate the chemoselective modification of
      12 complex molecules that contain a range of reactive functional groups. We also
      show the utility of this connection with both protease-cleavable and reductively
      cleavable antibody-drug conjugates that were effective and stable in vitro and in
      vivo. Studies with a tertiary-amine-containing antibiotic show that the resulting
      antibody-antibiotic conjugate provided appropriate stability and release
      characteristics and led to an unexpected improvement in activity over the
      conjugates previously connected via a carbamate.

PMID- 27874861
TI  - The scope and mechanism of palladium-catalysed Markovnikov alkoxycarbonylation of
      alkenes.
AB  - Hydroesterification reactions represent a fundamental type of carbonylation
      reaction and constitute one of the most important industrial applications of
      homogeneous catalysis. Over the past 70 years, numerous catalyst systems have
      been developed that allow for highly linear-selective (anti-Markovnikov)
      reactions and are used in industry to produce linear carboxylates starting from
      olefins. In contrast, a general catalyst system for Markovnikov-selective
      alkoxycarbonylation of aliphatic olefins remains unknown. In this paper, we show
      that a specific palladium catalyst system consisting of PdX2/N-phenylpyrrole
      phosphine (X, halide) catalyses the alkoxycarbonylation of various alkenes to
      give the branched esters in high selectivity (branched selectivity up to 91%).
      The observed (and unexpected) selectivity has been rationalized by density
      functional theory computation that includes a dispersion correction.

PMID- 27874863
TI  - Antibody-drug conjugates: The missing link.

PMID- 27874862
TI  - A decarboxylative approach for regioselective hydroarylation of alkynes.
AB  - Regioselective activation of aromatic C-H bonds is a long-standing challenge for
      arene functionalization reactions such as the hydroarylation of alkynes. One
      possible solution is to employ a removable directing group that activates one of
      several aromatic C-H bonds. Here we report a new catalytic method for
      regioselective alkyne hydroarylation with benzoic acid derivatives during which
      the carboxylate functionality directs the alkyne to the ortho-C-H bond with
      elimination in situ to form a vinylarene product. The decarboxylation stage of
      this tandem sequence is envisioned to proceed with the assistance of an ortho
      alkenyl moiety, which is formed by the initial alkyne coupling. This ruthenium
      catalysed decarboxylative alkyne hydroarylation eliminates the common need for
      pre-existing ortho-substitution on benzoic acids for substrate activation,
      proceeds under redox-neutral and relatively mild conditions, and tolerates a
      broad range of synthetically useful aromatic functionality. Thus, it
      significantly increases the synthetic utility of benzoic acids as easily
      accessible aromatic building blocks.

PMID- 27874864
TI  - New ligands for nickel catalysis from diverse pharmaceutical heterocycle
      libraries.
AB  - Ligands are essential for controlling the reactivity and selectivity of reactions
      catalysed by transition metals. Access to large phosphine ligand libraries has
      become an essential tool for the application of metal-catalysed reactions
      industrially, but these existing libraries are not well suited to new catalytic
      methods based on non-precious metals (for example, Ni, Cu and Fe). The
      development of the requisite nitrogen- and oxygen-based ligand libraries lags far
      behind that of the phosphines and the development of new libraries is anticipated
      to be time consuming. Here we show that this process can be dramatically
      accelerated by mining for new ligands in a typical pharmaceutical compound
      library that is rich in heterocycles. Using this approach, we were able to screen
      a structurally diverse set of compounds with minimal synthetic effort and
      identify several new ligand classes for nickel-catalysed cross-electrophile
      coupling. These new ligands gave improved yields for challenging cross-couplings
      of pharmaceutically relevant substrates compared with those of those of
      previously published ligands.

PMID- 27874867
TI  - Einsteinium declassified.

PMID- 27874865
TI  - Direct observation of subpicosecond vibrational dynamics in photoexcited
      myoglobin.
AB  - Determining the initial pathway for ultrafast energy redistribution within
      biomolecules is a challenge, and haem proteins, for which energy can be deposited
      locally in the haem moiety using short light pulses, are suitable model systems
      to address this issue. However, data acquired using existing experimental
      techniques that fail to combine sufficient structural sensitivity with adequate
      time resolution have resulted in alternative hypotheses concerning the interplay
      between energy flow among highly excited vibrational levels and potential
      concomitant electronic processes. By developing a femtosecond-stimulated Raman
      set-up, endowed with the necessary tunability to take advantage of different
      resonance conditions, here we visualize the temporal evolution of energy
      redistribution over different vibrational modes in myoglobin. We establish that
      the vibrational energy initially stored in the highly excited Franck-Condon
      manifold is transferred with different timescales into low- and high-frequency
      modes, prior to slow dissipation through the protein. These findings demonstrate
      that a newly proposed mechanism involving the population dynamics of specific
      vibrational modes settles the controversy on the existence of transient
      electronic intermediates.

PMID- 27874866
TI  - Oxadiazole grafts in peptide macrocycles.
AB  - Synthetic methods that provide control over macrocycle conformation and, at the
      same time, mitigate the polarity of peptide bonds represent valuable tools for
      the discovery of new bioactive molecules. Here, we report a macrocyclization
      reaction between a linear peptide, an aldehyde and (N
      isocyanimino)triphenylphosphorane. This process generates head-to-tail cyclic
      peptidomimetics in a single step. This method is tolerant to variation in the
      peptide and aldehyde components and has been applied for the synthesis of 15-, 18
      , 21- and 24-membered rings. The resulting peptide macrocycles feature a 1,3,4
      oxadiazole and a tertiary amine in their scaffolds. This non-canonical backbone
      region acts as an endocyclic control element that promotes and stabilizes a
      unique intramolecular hydrogen-bond network and can lead to macrocycles with
      conformationally rigid turn structures. Oxadiazole-containing macrocycles can
      also display a high passive membrane permeability, an important property for the
      development of bioavailable peptide-based therapeutics.

PMID- 27874868
TI  - Macrocyclic peptides: Tying up loose ends.

PMID- 27874870
TI  - 2016 Nobel Prize in Chemistry: Molecular machines.

PMID- 27874869
TI  - Oriented electric fields as future smart reagents in chemistry.
AB  - Oriented external electric fields (OEEFs) as 'smart reagents' are no longer a
      theoretical dream. Here, we discuss the wide-ranging potential of using OEEFs to
      catalyse and control a variety of non-redox reactions and impart selectivity at
      will. An OEEF along the direction of electron reorganization (the so-called
      reaction axis) will catalyse nonpolar reactions by orders of magnitude, control
      regioselectivity and induce spin-state selectivity. Simply flipping the direction
      of the OEEF or orienting it off of the reaction axis, will control at will the
      endo/exo ratio in Diels-Alder reactions and steps in enzymatic cycles. This
      Perspective highlights these outcomes using theoretical results for hydrogen
      abstraction reactions, epoxidation of double bonds, C-C bond forming reactions,
      proton transfers and the cycle of the enzyme cytochrome P450, as well as recent
      experimental data. We postulate that, as experimental techniques mature, chemical
      syntheses may become an exercise in zapping oriented molecules with OEEFs.

PMID- 27874872
TI  - Mechanically controlled quantum interference in individual pi-stacked dimers.
AB  - Recent observations of destructive quantum interference in single-molecule
      junctions confirm the role of quantum effects in the electronic conductance
      properties of molecular systems. These effects are central to a broad range of
      chemical and biological processes and may be beneficial for the design of single
      molecule electronic components to exploit the intrinsic quantum effects that
      occur at the molecular scale. Here we show that destructive interference can be
      turned on or off within the same molecular system by mechanically controlling its
      conformation. Using a combination of ab initio calculations and single-molecule
      conductance measurements, we demonstrate the existence of a quasiperiodic
      destructive quantum-interference pattern along the breaking traces of pi-stacked
      molecular dimers. The results demonstrate that it is possible to control the
      molecular conductance over more than one order of magnitude and with a sub
      angstrom resolution by exploiting the subtle structure-property relationship of
      pi-stacked dimers.

PMID- 27874871
TI  - Mass spectrometry captures off-target drug binding and provides mechanistic
      insights into the human metalloprotease ZMPSTE24.
AB  - Off-target binding of hydrophobic drugs can lead to unwanted side effects, either
      through specific or non-specific binding to unintended membrane protein targets.
      However, distinguishing the binding of drugs to membrane proteins from that of
      detergents, lipids and cofactors is challenging. Here, we use high-resolution
      mass spectrometry to study the effects of HIV protease inhibitors on the human
      zinc metalloprotease ZMPSTE24. This intramembrane protease plays a major role in
      converting prelamin A to mature lamin A. We monitored the proteolysis of
      farnesylated prelamin A peptide by ZMPSTE24 and unexpectedly found retention of
      the C-terminal peptide product with the enzyme. We also resolved binding of zinc,
      lipids and HIV protease inhibitors and showed that drug binding blocked prelamin
      A peptide cleavage and conferred stability to ZMPSTE24. Our results not only have
      relevance for the progeria-like side effects of certain HIV protease inhibitor
      drugs, but also highlight new approaches for documenting off-target drug binding.

PMID- 27874874
TI  - C-H activation: Good things come in threes.

PMID- 27874873
TI  - Enabling singlet fission by controlling intramolecular charge transfer in pi
      stacked covalent terrylenediimide dimers.
AB  - When an assembly of two or more molecules absorbs a photon to form a singlet
      exciton, and the energetics and intermolecular interactions are favourable, the
      singlet exciton can rapidly and spontaneously produce two triplet excitons by
      singlet fission. To understand this process is important because it may prove to
      be technologically significant for enhancing solar-cell performance. Theory
      strongly suggests that charge-transfer states are involved in singlet fission,
      but their role has remained an intriguing puzzle and, up until now, no molecular
      system has provided clear evidence for such a state. Here we describe a
      terrylenediimide dimer that forms a charge-transfer state in a few picoseconds in
      polar solvents, and undergoes equally rapid, high-yield singlet fission in
      nonpolar solvents. These results show that adjusting the charge-transfer-state
      energy relative to those of the exciton states can serve to either inhibit or
      promote singlet fission.

PMID- 27874875
TI  - Novel aspects of autoimmunity.

PMID- 27874876
TI  - Immunology & Cell Biology Publication of the Year Awards 2015.

PMID- 27874877
TI  - Low-dose radiotherapy for primary cutaneous anaplastic large-cell lymphoma while
      on low-dose methotrexate.
AB  - Primary cutaneous anaplastic large-cell lymphoma (pcALCL) is part of a spectrum
      of CD30+ primary cutaneous lymphoproliferative disorders (pcLPDs) that also
      includes lymphomatoid papulosis (LyP). Localized radiotherapy at doses of 34 to
      44 Gy is first-line treatment of pcALCL, but the use of low-dose radiotherapy for
      pcALCL has not been reported. We present the case of a patient with a history of
      pcALCL/LyP who was treated with low-dose radiotherapy while on oral low-dose
      methotrexate (MTX) once weekly. This report suggests that low-dose radiotherapy
      can be an effective palliative treatment of pcALCL. Low-dose radiotherapy may
      offer certain advantages over traditional radiotherapy, such as a more economical
      and efficient treatment for patients, potentially fewer short-term and long-term
      side effects, and the potential for concomitant use with low-dose MTX.

PMID- 27874878
TI  - Presenting treatment safety data: subjective interpretations of objective
      information.
AB  - Educating patients about the risks of treatment is obligatory. An inherent
      problem with risk education is that patients can become terrified of rare risks
      associated with the treatment, resulting in possible treatment refusal, poor
      adherence, and continued disease symptoms. Such fears are a common obstacle
      observed with the use of biologic medications to treat psoriasis. In this
      article, we use graphical presentation of psoriasis safety data to illustrate how
      patients subjectively interpret objective information. Different ways of
      presenting safety data graphically include the use of truncated, full, and
      inversed y-axes, resulting in certain likely perceptions by the patient. Despite
      a physician's best intentions to give a patient objective information, patients
      will subjectively interpret objective safety data. Therefore, when presenting
      information, whether in the form of numerical descriptions or graphical
      presentations, the physician must use his/her best judgment to determine how to
      present safety data to patients to ensure their well-being and properly inform
      them about their treatment options.

PMID- 27874879
TI  - Bullous pemphigoid associated with a lymphoepithelial cyst of the pancreas.
AB  - Bullous pemphigoid (BP) is an acquired, autoimmune, subepidermal blistering
      disorder. A possible paraneoplastic association has been suggested; however,
      debate remains regarding the precise relationship of these neoplasms with BP. We
      present a case of recalcitrant BP in a 67-year-old man with a pancreatic neoplasm
      that was found to be a lymphoepithelial cyst. Immunoperoxidase staining of the
      cyst demonstrated C3d along the basement membrane of the stratified squamous
      epithelium, suggesting that the BP may have involved the lymphoepithelial cyst
      itself. Shortly after excision of the cyst, BP rapidly resolved without any
      immunosuppressive treatment, raising the possibility that the immunologic process
      involving the lymphoepithelial cyst of the pancreas was the inciting factor for
      the patient's cutaneous disease. Although rare, some cases of BP may be a
      paraneoplastic process. A thorough screening via patient history and directed
      laboratory studies may be warranted in recalcitrant cases.

PMID- 27874880
TI  - What makes feedback productive?

PMID- 27874881
TI  - Crusted plaque in the umbilicus.

PMID- 27874883
TI  - Exploration of modern military research resources.
AB  - This article outlines the unique resources available in the US Military to
      investigate epidemiologic trends, disease pathology, and clinical outcomes. These
      resources are available to military researchers and civilian collaborators and
      provide an invaluable research platform.

PMID- 27874882
TI  - Pruritic papules on the scalp and arms.

PMID- 27874884
TI  - The Proposed Rule and payments for 2017: the good, the bad, and the ugly.

PMID- 27874885
TI  - Patient-reported outcomes of azelaic acid foam 15% for patients with
      papulopustular rosacea: secondary efficacy results from a randomized, controlled,
      double-blind, phase 3 trial.
AB  - Patient-reported treatment outcomes are important for evaluating the impact of
      drug therapies on patient experience. A randomized, double-blind, vehicle
      controlled, parallel-group, multicenter, phase 3 study was conducted in 961
      participants to assess patient perception of efficacy, utility, and effect on
      quality of life (QOL) of an azelaic acid (AzA) 15% foam formulation for the
      treatment of papulopustular rosacea (PPR). Secondary end points included patient
      reported global assessment of treatment response, global assessment of
      tolerability, and opinion on cosmetic acceptability and practicability of product
      use. Quality of life assessments included the Dermatology Quality of Life Index
      (DLQI) and Rosacea Quality of Life Index (RosaQOL). Self-reported global
      assessment of treatment response favored AzA foam over vehicle foam (P<.001),
      with 57.2% of the AzA foam group reporting excellent or good improvement versus
      44.7% in the vehicle foam group. Tolerability was rated excellent or good in
      67.8% of the AzA foam group versus 78.2% of the vehicle foam group. Mean overall
      DLQI scores at end of treatment (EoT) were improved (P=.018) in favor of the AzA
      foam group compared with the vehicle foam group. Both treatment groups showed
      improvements in RosaQOL. Treatment with AzA foam was associated with improved QOL
      and meaningful reductions in the patient-perceived burden of PPR, which
      correlates with earlier reported primary end points of this study and supports
      the inclusion of patient perspectives in studies evaluating the effects of
      topical dermatologic treatments.

PMID- 27874886
TI  - Beaded papules along the eyelid margins.

PMID- 27874887
TI  - Blaschkoid unilateral patch on the chest.

PMID- 27874888
TI  - Epidermodysplasia verruciformis and the risk for malignancy.

PMID- 27874890
TI  - Diagnosis of a rapidly growing preauricular nodule: chondroid syringoma or
      pleomorphic adenoma?

PMID- 27874889
TI  - Acute inflammatory skin reaction during neutrophil recovery after antileukemic
      therapy.

PMID- 27874891
TI  - Recurrent cerebriform connective tissue nevus on the foot of a patient with
      Proteus syndrome.

PMID- 27874892
TI  - Idiopathic livedo racemosa presenting with splenomegaly and diffuse
      lymphadenopathy.
AB  - Sneddon syndrome (SS) is a rare condition and the diagnosis is made only when
      other more common disease entities have been excluded. Common manifestations in
      SS patients include hypertension, coronary artery disease, venous thrombosis,
      miscarriages, psychiatric disturbances, and arterial and venous thrombotic
      events. Most patients present in their early 30s with classic neurovascular and
      dermatologic signs. Currently, the main criteria for the diagnosis of SS include
      livedo racemosa, focal neurological deficits or evidence of stroke on magnetic
      resonance imaging, or characteristic vascular alterations seen on biopsy. We
      present the case of a 37-year-old woman with extensive livedo racemosa, chronic
      migraine headaches, splenomegaly, and lymphadenopathy. Cutaneous biopsies
      demonstrated a superficial perivascular lymphocytic infiltrate without the
      subendothelial proliferative changes or fibrosis seen in some patients with SS.
      The patient's medical history suggested idiopathic livedo racemosa with possible
      full progression to SS. This case highlights the variability in the clinical
      presentation of SS and that the disease often can be diagnosed before
      neurovascular events. Earlier diagnosis can lead to prevention of chronic
      occlusive neurovascular manifestations and irreversible damage such as myocardial
      infarction and stroke. Familiarity with the highly variable early course of SS
      can aid in diagnosis and reduction of morbidity and mortality that is associated
      with this disease.

PMID- 27874894
TI  - How to increase patient adherence to therapy.
AB  - How do we increase patient adherence to therapy? As dermatologists, we will see
      thousands of patients over the course of our careers, most with treatable
      conditions that will improve with therapy and others with chronic or genetic
      conditions that will at least be made more tolerable with therapy. Approximately
      half of patients with chronic conditions are adherent to therapy. Why some
      patients adhere to treatment and others do not can be difficult to understand.
      The emotional makeup, culture, family background, socioeconomic status, and
      motivation of each person is unique, which leads to complexity. This column is
      not meant to answer a question that is both complex and broad; rather, it is
      meant to survey and summarize the literature on this enigmatic topic.

PMID- 27874893
TI  - Abnormal wound healing related to high-dose systemic corticosteroid therapy in a
      patient with Ehlers-Danlos syndrome benign hypermobility Type.
AB  - The adverse impact of chronic corticosteroid therapy on wound healing has been
      well characterized, as has abnormal wound healing known to occur in the classic
      type of Ehlers-Danlos syndrome (EDS). In contrast, abnormal wound healing is
      absent in cases of EDS benign hypermobility type (EDS-BHT). We present the case
      of a patient with EDS-BHT with no history of abnormal wound healing who developed
      large nonhealing ulcers to sites of minor trauma after initiating therapy with
      high-dose systemic corticosteroids for dermatomyositis. This case provides a
      dramatic illustration of the effects of chronic systemic corticosteroids on skin
      fragility and wound healing in a patient with an underlying genetic defect of the
      connective tissue.

PMID- 27874895
TI  - CO2 reduction with Re(i)-NHC compounds: driving selective catalysis with a
      silicon nanowire photoelectrode.
AB  - The CO2-reduction activity of two Re(i)-NHC complexes is investigated employing a
      silicon nanowire photoelectrode to drive catalysis. Photovoltages greater than
      440 mV are observed along with excellent selectivity towards CO over H2
      formation. The observed selectivity towards CO production correlates with strong
      adsorption of the catalysts on the photoelectrode surface.

PMID- 27874896
TI  - Unusual acid-base properties of the P4 molecule in hydrogen-, halogen-, and
      pnicogen-bonded complexes.
AB  - Ab initio MP2/aug'-cc-pVTZ calculations have been carried out to investigate
      hydrogen bonding, halogen bonding, and pnicogen bonding involving tetrahedral P4
      and the FH, ClH, and FCl molecules. P4 has three unique interaction sites: at a
      vertex (designated the P1 atom); at an edge (the P2-P3 bond); and at the P2-P3-P4
      face. The uniqueness of molecular P4 is its ability to act as an electron donor
      and an electron acceptor at the same site, except for the P2-P3 bond, which is
      only an electron donor. FCl and FH form five different complexes with P4, but ClH
      forms only three. The type of complex formed and its binding energy depend on
      both the interaction site of molecular P4 and the interacting molecule. For all
      complexes with FH, ClH, and FCl, the binding energies at a given site with the P4
      molecule acting as the base are greater than the binding energies when P4 is the
      acid. Thus, P4 is a better electron donor than an electron acceptor. Charge
      transfer interactions and EOM-CCSD spin-spin coupling constants across hydrogen,
      halogen, and pnicogen bonds are reported for all of the P4 complexes. Relative to
      1J(Pi-Pj) in molecular P4, 1J(P1-P2) coupling constants decrease in absolute
      value and 1J(P2-P3) coupling constants increase in pnicogen-bonded complexes and
      the complex with FCl that has a PF halogen bond. Absolute values of 1J(P1-P2)
      increase and those of 1J(P2-P3) decrease in hydrogen-bonded complexes and
      complexes with PCl halogen bonds. 1J(P1-P2) and 1J(P2-P3) exhibit a single linear
      correlation with the corresponding Pi-Pj distances.

PMID- 27874897
TI  - Extraction of Nb(v) by quaternary ammonium-based solvents: toward organic
      hexaniobate systems.
AB  - Solvent extraction of Nb(v) from alkaline aqueous media using quaternary ammonium
      solutions, especially Aliquat(r) 336 diluted in an aliphatic diluent, was
      investigated. The hexaniobate ions (HxNb6O19x-8) were extracted into the organic
      phase with very high yields at room temperature and within a few minutes,
      affording easy access to organic solutions of hexaniobates. Several parameters
      were found to influence the extraction of HxNb6O19x-8 including the nature and
      concentration of alkali cations, confirming subtle effects previously described
      for polyoxoniobates such as ion-pairing with alkali ions. The extraction of
      HxNb6O19x-8 with Aliquat(r) 336 is also influenced if competing anions are
      present in the aqueous phase (NO3-, Cl-, C2O42-, SO42- and CO32-) and varies with
      the pH mainly due to the competitive extraction of hydroxide ions at high pH. The
      co-extraction of sodium ions with HxNb6O19x-8 was observed as well as the co
      extraction of water molecules, suggesting a self-association of the extractant.
      The proposed liquid-liquid extraction generic system paves the way for innovative
      niobium (and potentially tantalum) hydrometallurgical processes and it may also
      afford more direct routes for exploring the chemistry of hexaniobates in organic
      solvents.

PMID- 27874899
TI  - Exposure assessment of natural uranium from drinking water.
AB  - The uranium concentration in the drinking water of the residents of the Jaipur
      and Ajmer districts of Rajasthan has been measured for exposure assessment. The
      daily intake of uranium from the drinking water for the residents of the study
      area is found to vary from 0.4 to 123.9 MUg per day. For the average uranium
      ingestion rate of 35.2 MUg per day for a long term exposure period of 60 years,
      estimations have been made for the retention of uranium in different body organs
      and its excretion with time using ICRP's biokinetic model of uranium. Radioactive
      and chemical toxicity of uranium has been reported and discussed in detail in the
      present manuscript.

PMID- 27874898
TI  - Polymer-mediated ternary supramolecular interactions for sensitive detection of
      peptides.
AB  - A combination of donor-acceptor and electrostatic interactions in a three
      component supramolecular system has been shown to form the basis for selective
      and sensitive detection of peptides. Different substituents in the polymer and
      the detection matrix were compared to demonstrate that the favorable donor
      acceptor interactions explain the observed signal enhancement. The ternary
      supramolecular interactions discovered in this work are enabled by the self
      packing behavior of amphiphilic homopolymers and their ability to mediate
      interactions between the detection matrix and peptide that facilitate sensitive
      detection of peptides.

PMID- 27874900
TI  - Photosensitive organic field effect transistors: the influence of ZnPc morphology
      and bilayer dielectrics for achieving a low operating voltage and low bias stress
      effect.
AB  - Photosensitive-organic field effect transistors (PS-OFETs) based on a morphology
      controlled zinc phthalocyanine (ZnPc) layer, with an inorganic-organic bilayer
      gate dielectric system, fabricated on a glass substrate showed remarkable
      efficiency as light sensors at various incident optical powers. The indium tin
      oxide (ITO) and Si/SiO2 free low-cost OFET devices show low bias stress and a
      reduced operating voltage with aluminum oxide and poly(methyl methacrylate)
      (Al2O3/PMMA) as bilayer gate dielectrics and copper (Cu) as a top contact. They
      exhibit excellent p-channel behavior with a remarkable photo-responsivity of
      2679.40 A W-1 and a photo-ON/OFF current ratio of 933.56 with a very low
      operating voltage (0 to -8 V), which have not been observed previously. The bias
      stress effect of the device was investigated under both light and dark conditions
      in a vacuum. It was observed that the effect of the stress is extremely small in
      the presence of light (a decay of IDS of ~ 20% after 30 min) compared to the
      dark, with a characteristic carrier relaxation time tau' ~ 104 s. This device
      with high electrical stability under ambient conditions and a low threshold
      voltage under constant electrical bias stress is expected to have potential
      applications in optoelectronic devices and energy efficient sensors.

PMID- 27874901
TI  - The assembly of thiophene-based bis-pyridyl-bis-amide CoII coordination polymers
      and their polypyrrole-functionalized hybrid materials for boosting their
      photocatalytic performances.
AB  - Herein, a series of multifunctional CoII coordination polymer (CP) materials,
      which were based on a new semi-rigid thiophene-containing bis-pyridyl-bis-amide
      N,N'-bis(pyridine-3-yl)thiophene-2,5-dicarboxamide (3-bptpa) ligand and different
      polycarboxylates, namely, [Co(3-bptpa)(1,3-BDC)].2H2O (CP1), [Co(3-bptpa)(5
      MIP)].2H2O (CP2), [Co(3-bptpa)(1,3,5-HBTC)] (CP3), [Co(3-bptpa)(5-NIP)].2H2O
      (CP4) and [Co(3-bptpa)(1,3-BDC)].2H2O (CP5) (1,3-H2BDC = 1,3-benzenedicarboxylic
      acid, 5-H2MIP = 5-methylisophthalic acid, 1,3,5-H3BTC = 1,3,5
      benzenetricarboxylic acid, 5-H2NIP = 5-nitroisophthalic acid) and their
      polypyrrole (PPy)-functionalized hybrid materials PPy/CPn (n = 1, 2, 3, 4, 5),
      have been prepared. The CP materials were structurally characterized by single
      crystal X-ray diffraction analyses, IR spectra, UV-vis diffuse-reflectance
      spectra (DRS), powder X-ray diffraction (PXRD) and thermal gravimetric analyses
      (TG). The structural analyses indicate that CP1-CP4 reveal similar 2D networks.
      CP5 exhibits a 2-fold interpenetrating 3D alpha-Po framework. The PPy
      functionalized CP1-CP5 hybrid materials PPy/CPn were fabricated by the
      combination of micro-size CP particles and PPyvia a facile in situ chemical
      oxidation polymerization process under the initiation of ammonium persulfate
      (APS). The photocatalytic properties of CP1-CP5 and PPy/CPn hybrid materials have
      been investigated in detail. As a result, after being decorated with PPy, the
      photocatalytic properties of the hybrid materials, particularly PPy/CP3, have
      been observably enhanced for the degradation of methylene blue (MB) under visible
      light irradiation.

PMID- 27874902
TI  - Iridium(iii) phosphorescent complexes with dual stereogenic centers: single
      crystal, electronic circular dichroism evidence and circularly polarized
      luminescence properties.
AB  - Iridium complexes with a chiral metal center and chiral carbons, Lambda/Delta
      (dfppy)2Ir(chty-R) and Lambda/Delta-(dfppy)2Ir(chty-S), were synthesized and
      characterized. These isomers have the same steady-state photophysical properties,
      and obvious offsets in ECD spectra highlight both the chiral sources. Each
      enantiomeric couple shows mirror-image CPL bands with a dissymmetry factor in the
      order of 10-3.

PMID- 27874908
TI  - Rivaroxaban for Thromboprophylaxis After Nonelective Orthopedic Trauma Surgery in
      Switzerland.
AB  - This study investigated the effectiveness and the outcomes of rivaroxaban vs the
      standard of care for venous thromboembolic prophylaxis in patients undergoing
      fracture-related surgery. A total of 413 patients undergoing fracture-related
      surgery from 9 Swiss orthopedic and trauma centers were enrolled. The authors
      selected the type of venous thromboembolic prophylaxis according to standardized
      medical practice at the participating centers before the inclusion of patients:
      208 patients received rivaroxaban and 205 received the standard of care. Data on
      symptomatic thromboembolic and bleeding events, surgery-related complications,
      death, adverse events, time to mobilization, and hospital discharge were
      collected. Symptomatic thromboembolic events were reported in 1 patient (0.5%)
      and 2 patients (1.0%) and treatment-emergent major bleeding events were reported
      in 1 patient (0.5%) and 2 patients (1.0%) receiving rivaroxaban and the standard
      of care, respectively. The durations of hospital stay and venous thromboembolic
      prophylaxis were similar in the 2 groups. In both groups, adverse events related
      to venous thromboembolic prophylaxis were reported in 12 patients. The proportion
      of patients with minor and major fracture surgery was 74.3% and 25.7%,
      respectively. In patients undergoing minor fracture surgery receiving rivaroxaban
      (n=167) and the standard of care (n=140), no symptomatic thromboembolic events
      and no major bleeding events were reported. Outcomes of this study indicate that
      rivaroxaban might be an appropriate oral alternative for venous thromboembolic
      prophylaxis in routine medical care after fracture-related major and minor
      surgery. Reported results were comparable to those from other large-scale,
      noninterventional and randomized controlled studies. [Orthopedics. 2017;
      40(2):109-116.].

PMID- 27874909
TI  - Risk Factors for Intraoperative Proximal Femoral Fracture During Primary
      Cementless THA.
AB  - Intraoperative proximal femoral fracture, one of the most common complications of
      total hip arthroplasty (THA), occurs more often in cementless procedures and can
      affect rehabilitation, hospitalization time, and cost of treatment. The goal of
      this study was to identify risk factors for intraoperative proximal femoral
      fracture in THA to identify high-risk groups preoperatively and minimize the
      incidence of this complication. This nested case-control study included 904
      primary cementless THA procedures (769 patients) performed between January 2009
      and July 2015. Of this group, 24 fractures occurred, accounting for 2.65% of
      cases. Predisposing factors for intraoperative proximal femoral fracture from the
      medical records included patient sex, diagnosis of osteoarthritis, operated on
      hip (left or right), type of implant, alcohol consumption, operative approach,
      age, and body mass index. The Noble classification, Dorr classification, and
      Metaphyseal-Diaphyseal Index score measured by picture archiving and
      communication systems were used to evaluate the anatomy and morphologic features
      of the proximal femur. A multivariate analysis was performed to evaluate
      potential risk factors for fracture during THA, including anterolateral (modified
      Hardinge) approach, use of the Corail (DePuy, Warsaw, Indiana) stem, Metaphyseal
      Diaphyseal Index score, age, and sex. A Corail stem, the anterolateral approach,
      advanced age, and a low Metaphyseal-Diaphyseal Index score were associated with
      increased risk of fracture. All fractures were treated with cerclage wire
      techniques, and none has required revision to date. [Orthopedics. 2017;
      40(2):e281-e287.].

PMID- 27874910
TI  - Short Versus Long Cephalomedullary Nails for Pertrochanteric Hip Fracture.
AB  - This study compared patients who underwent treatment with short or long
      cephalomedullary nails with integrated cephalocervical screws and linear
      compression. Patients with AO/OTA 31-A2 or A3 pertrochanteric fractures treated
      with either short (n=72) or long (n=97) InterTAN (Smith & Nephew, Memphis,
      Tennessee) cephalomedullary nails were reviewed. Information on perioperative
      measures (estimated blood loss, surgical time, and fluoroscopy time) and
      postoperative orthopedic complications (infection, implant failure, screw cutout,
      and periprosthetic femur fracture) was included. Estimated blood loss (short
      nail, 161 mL; long nail, 208 mL; P=.002) and surgical time (short nail, 64
      minutes; long nail, 83 minutes; P=.001) were lower in the short nail group. There
      were no differences in fluoroscopy time (short nail, 90 seconds; long nail, 142
      seconds; P=.071) or rates of infection (short nail, 1.4%; long nail, 3.1%;
      P=.637) or overall orthopedic complications (short nail, 11.1%; long nail, 9.3%;
      P=.798) between the 2 groups. The long nail group had a trend toward more screw
      cutouts (long nail, 5.2%; short nail, 0.0%; P=.134) but fewer periprosthetic
      femur fractures (short nail, 8.3%; long nail, 0.0%; P=.013). This study found a
      similar overall rate of orthopedic complications between short and long nails
      with integrated cephalocervical screws and linear compression. These results
      confirm the suspected advantages of short nails, including faster surgery and
      less blood loss; however, the rate of periprosthetic femur fracture remains high,
      despite changes to implant design. [Orthopedics. 2017; 40(2):83-88.].

PMID- 27874911
TI  - Outcomes of ACL Reconstruction With Fixed Versus Variable Loop Button Fixation.
AB  - Suspensory femoral fixation of anterior cruciate ligament (ACL) grafts with fixed
      loop button and variable loop button devices has gained popularity for ACL
      reconstruction. This study examined these 2 methods of fixation to determine
      their effect on graft laxity and patient-reported outcome scores. A database
      search was performed to identify patients who had undergone ACL reconstruction
      with either a fixed loop or a variable loop button technique performed by the
      primary surgeon. Lysholm, Tegner, and 12-Item Short Form Health Survey scores
      were obtained, and KT-1000 knee ligament arthrometer (MEDmetric, San Diego,
      California) mechanical knee testing was performed. Results were compared with the
      uninjured knee. Of the 112 patients who were identified, 91 met the study
      criteria. Of these patients, 57 completed KT-1000 knee testing, 33 in the
      variable group and 24 in the fixed group. The average KT-1000 value for the
      variable group was 0.38 mm, and the average for the closed group was 0.92 mm
      (P=.19; 95% confidence interval, -0.28 to 1.35). Among the 19 patients in the
      variable group and the 13 in the closed group who completed the subjective
      outcomes questionnaires, no statistically significant difference was found.
      Clinically lax knees (KT-1000>3 mm) were found in 6.1% and 12.5% of patients in
      the variable group and the fixed group, respectively (P=.2). The variable group
      had a rerupture rate of 4.7%, whereas the fixed group had a rerupture rate of
      8.7% (P=.21). The study found no statistical difference in ACL graft laxity or
      postoperative functional outcomes between grafts fixed with the variable loop or
      fixed loop button technique. [Orthopedics. 2017; 40(2):e275-e280.].

PMID- 27874912
TI  - Corticosteroid Injections: A Review of Sex-Related Side Effects.
AB  - Corticosteroid injections are used as a nonoperative modality to combat acute
      inflammation when conservative treatments fail. As female patients are regularly
      seen by orthopedic physicians, it is essential to identify and understand
      potential sex-related side effects. The aim of this article is to examine
      available literature for sex-related side effects of orthopedic-related
      corticosteroid injections. Although the incidence is low, sex-related side
      effects, such as abnormal menstruation, lactation disturbances, facial flushing,
      and hirsutism, are associated with corticosteroid injections. Physicians should
      be aware of these female-specific side effects and relay this information as part
      of the informed consent process. [Orthopedics. 2017; 40(2):e211-e215.].

PMID- 27874913
TI  - Metal-on-Metal Total Hip Arthroplasty: Quality of Online Patient Information.
AB  - Metal-on-metal total hip arthroplasty (THA) has generated much attention in the
      media because of early failure of certain implant systems. This study assessed
      the quality, accuracy, and readability of online information on metal-on-metal
      THA. The search terms "metal-on-metal hip replacement" and "metal hip
      replacement" were entered into the 3 most popular search engines. Information
      quality was assessed with the DISCERN score and a specific metal-on-metal THA
      content score. Accuracy of information was assessed with a customized score.
      Readability of the websites was assessed with the Flesch-Kincaid grade level
      score. A total of 61 unique websites were assessed. For 56% of websites, the
      target audience was patients. Media or medicolegal sources accounted for 44% of
      websites. As assessed by DISCERN (range, 16-80) and metal-on-metal THA (range, 0
      25) scores, quality of the websites was moderate at best (47.1 and 9.6,
      respectively). Accuracy (range, 0-8) of the information presented also was
      moderate, with a mean score of 6.6. Media and medicolegal websites had the lowest
      scores for both quality and accuracy, despite making up the greatest proportion
      of sites assessed. Only 1 website (2%) had a Flesch-Kincaid grade level at or
      less than the recommended level of 8th grade. This study found that online
      information on metal-on-metal THA was of poor quality, often was inaccurate, and
      was presented at an inappropriately high reading level, particularly for media
      and medicolegal websites. Health care providers should counsel patients on the
      quality of information available and recommend appropriate online resources.
      [Orthopedics. 2017; 40(2):e262-e268.].

PMID- 27874915
TI  - ?

PMID- 27874914
TI  - Surgical Cost Disclosure May Reduce Operating Room Expenditures.
AB  - Health care expenditures are rising in the United States. Recent policy changes
      are attempting to reduce spending through the development of value-based payment
      systems that rely heavily on cost transparency. This study was conducted to
      investigate whether cost disclosure influences surgeons to reduce operating room
      expenditures. Beginning in 2012, surgeon scorecards were distributed at a
      regional health care system. The scorecard reported the actual direct supply cost
      per case for a specific procedure and compared each surgeon's data with those of
      other surgeons in the same subspecialty. Rotator cuff repair was chosen for
      analysis. Actual direct supply cost per case was calculated quarterly and
      collected over a 2-year period. Surgeons were given a questionnaire to determine
      their interest in the scorecard. Actual direct supply cost per rotator cuff
      repair procedure decreased by $269 during the study period. A strong correlation
      (R2=0.77) between introduction of the scorecards and cost containment was
      observed. During the study period, a total of $39,831 was saved. Of the surgeons
      who were queried, 89% were interested in the scorecard and 56% altered their
      practice as a result. Disclosure of surgical costs may be an effective way to
      control operating room spending. The findings suggest that providing physicians
      with knowledge about their surgical charges can alter per-case expenditures.
      [Orthopedics. 2017; 40(2):e269-e274.].

PMID- 27874916
TI  - Treatment options for permanent teeth with deep caries.
AB  - The goal of this narrative review was to summarize and compare treatment options
      for permanent teeth carious lesions that are radiographically close to the pulp
      chamber. Thanks to adhesive restorative materials, minimally invasive approaches
      are possible. In this context, the old question arises as to whether caries must
      be excavated completely, i.e., down to hard dentin, or whether it could be
      advantageous to leave some soft dentin, or even merely seal the whole lesion. To
      answer this question, the microbiological aspects of the lesion must be
      considered, along with the immunological response in the dental pulp, with the
      concurrent possible negative outcomes for the patient. Both aspects are
      considered in this review, and clinical studies comparing different treatment
      modalities are discussed. Situations in which calcium silicate cements could be
      advantageous over the gold standard calcium hydroxide preparations for covering
      the dentin/pulp wound are also discussed.

PMID- 27874917
TI  - ?
AB  - This script gives a pragmatic advice for dentists on pain control and anti
      inflammation treatment considering current literature and state of the art of
      analgesic treatment. Naproxen seems to be the feasible anti-inflammatory
      painkiller as it has a lower cardio-vascular risk profile compared to other
      NSAID. The higher gastrointestinal bleeding risk can be mitigated using proton
      pump inhibitors. Additionally, the duration of the drug effect of about 12?15
      hours allows excellent patient compliance and comfort in comparison to other
      NSAID.

PMID- 27874907
TI  - Natural products as mediators of disease.
AB  - Covering: up to 2016Humans are walking microbial ecosystems, each harboring a
      complex microbiome with the genetic potential to produce a vast array of natural
      products. Recent sequencing data suggest that our microbial inhabitants are
      critical for maintaining overall health. Shifts in microbial communities have
      been correlated to a number of diseases including infections, inflammation,
      cancer, and neurological disorders. Some of these clinically and diagnostically
      relevant phenotypes are a result of the presence of small molecules, yet we know
      remarkably little about their contributions to the health of individuals. Here,
      we review microbe-derived natural products as mediators of human disease.

PMID- 27874918
TI  - ?
AB  - Dental aplasia of heterogenous etiology may cause jaw growth disturbance,
      malocclusion, esthetic discontent and psychosocial impairment. By a case report
      of a young patient suffering from hypodontia, class II malocclusion and a deep
      bite the intricate interdisciplinary diagnosis- and treatment-protocol targeting
      the functional and esthetic rehabilitation is illustrated.

PMID- 27874919
TI  - ?
AB  - In a case report the stomatognathic rehabilitation of a patient with class III
      malocclusion and mandibular bilateral interdental gaps from the diagnosis and
      treatment planning through to the stepwise realization of the orthodontic,
      surgical and prosthetic treatment is presented. Explicit information about the
      proposed treatment, risks and the prospective outcome beforehand ensured the
      patient?s compliance during the extensive procedure.

PMID- 27874920
TI  - [Better intensive care outcomes for men than women especially in septic shock and
      after cardiac arrest].
AB  - Better intensive care outcomes for men than women especially in septic shock and
      after cardiac arrest In this study 11 764 intensive care admissions to Skane
      University Hospital in Sweden between 2008 and 2015 were studied for any gender
      differences in outcome for different diagnoses. As known from previous studies,
      men had more intensive care admissions and had a higher morbidity necessitating
      the use of risk adjusted mortality measures. Through a simple but new application
      of VLAD we found this risk-adjusted mortality measure to be more sensitive in
      detecting differences in mortality between groups than the more commonly used
      SMR. The main finding was somewhat surprisingly that intensive care outcomes are
      better for males than females. This difference was most marked in septic shock
      and post cardiac arrest and did not seem to be caused by unequal distribution of
      care. Our findings were also confirmed using a bootstrap technique on EMR-matched
      cohorts.

PMID- 27874921
TI  - ?

PMID- 27874923
TI  - [Brave new health care].

PMID- 27874922
TI  - [New model for the diagnosis of urinary tract infections proposed].

PMID- 27874924
TI  - [A provincial doctor and his fight against infectious diseases].

PMID- 27874925
TI  - ?

PMID- 27874926
TI  - [Swedish child health is doing well--but increased segregation and growing health
      care costs worries].

PMID- 27874927
TI  - [Far from equal stroke care].

PMID- 27874928
TI  - ?

PMID- 27874929
TI  - [The prioritization center: We welcome a dialogue on open priorities].

PMID- 27874930
TI  - [Time to remove health care from the issue about regions].

PMID- 27874931
TI  - [The county council's own drug trials provide unequal care].

PMID- 27874932
TI  - ?

PMID- 27874934
TI  - Effect of nitric oxide inhalation for the treatment of neonatal pulmonary
      hypertension.
AB  - OBJECTIVE: To investigate the effect of nitric oxide (NO) inhalation for the
      treatment of neonatal pulmonary hypertension. PATIENTS AND METHODS: Eighty-six
      patients with neonatal pulmonary hypertension who were treated for the first time
      Xuzhou Children's Hospital from January 2013 to January 2016 were selected and
      randomly divided into the observation group and control group, with 43 cases
      each. Patients in the control group were treated with high-frequency oscillatory
      ventilation, while those in the observation group were treated with high
      frequency oscillatory ventilation combined with inhalational NO therapy. The
      therapeutic effects were compared. RESULTS: Over time, fraction of inspired
      oxygen (FiO2) of patients in both groups decreased, and the FiO2 levels of
      patients in the observation group at the different time points were lower than
      those of the control group; oxygen pressure (PaO2) and oxygen saturation (SpO2)
      showed an upward trend; the PaO2 and SpO2 levels in the observation group were
      higher than those of the control group at all time points. Oxygenation index (OI)
      increased, and the OI levels of the observation group at each time point were
      higher than those of the control group. Pulmonary artery pressure decreased at
      each time point, and the levels in the observation group were lower than those of
      the control group. The differences were statistically significant (p < 0.05). The
      duration of mechanical ventilation, duration of oxygen therapy, and mortality in
      the observation group were significantly lower than those of the control group,
      and the differences were statistically significant (p < 0.05). CONCLUSIONS: Using
      NO inhalation to treat neonatal pulmonary hypertension can significantly improve
      oxygen supply, reduce pulmonary artery pressure, shorten treatment time, and
      reduce mortality. It is, therefore, worthy of clinical application.

PMID- 27874933
TI  - Vitamin D supplementation for osteoporosis in older adults: can we make it help
      better?
AB  - With the increase of the average age of our population, the incidence of diseases
      specific for older adults has been increasing. One of such diseases is
      osteoporosis. The true incidence of osteoporosis is unknown. But the estimates
      indicate that this disease affects wide proportions of the population, ranging in
      millions or even ten millions in large countries like the United States. As this
      poses a significant burden on the health care system, interventions that could
      prevent or treat this condition are in the focus of clinical research. Vitamin D,
      the determinant of bone health, has been tested in clinical studies as the agent
      to treat osteoporosis. Despite the progress, there is still some controversy
      about the targeted blood levels of vitamin D, most efficient way to supplement
      this vitamin, and clinical efficacy of this supplementation in the elderly.In the
      present review, we will highlight the metabolism of vitamin D and the
      aforementioned unresolved issues, as well as review the recent interventional
      studies on vitamin D supplementation. In the present review, we will highlight
      the metabolism of vitamin D and the aforementioned unresolved issues, as well as
      review the recent interventional studies on vitamin D supplementation.

PMID- 27874935
TI  - Effect of administration of Streptococcus salivarius K12 on the occurrence of
      streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media in 3
      years old children.
AB  - OBJECTIVE: Streptococcus salivarius K12 (BLIS K12) is a probiotic strain strongly
      antagonistic to the growth of Streptococcus pyogenes, the most important
      bacterial cause of pharyngeal infections in humans. Shown to colonize the oral
      cavity and to be safe for human use, BLIS K12 has previously been reported to
      reduce pharyngo-tonsillitis episodes in children or adults known to have
      experienced recurrent streptococcal infection. The present study was focussed
      upon evaluating the role of BLIS K12 in the control of streptococcal disease and
      acute otitis media in children attending the first year of kindergarten. PATIENTS
      AND METHODS: By randomization, 222 enrolled children attending the first year of
      kindergarten were divided into a treated group (N = 111) receiving for 6 months a
      daily treatment with BLIS K12 (Bactoblis(r)) and a control group (N = 111) who
      were monitored as untreated controls. During the 6 months of treatment and 3
      months of follow-up, the children were evaluated for treatment tolerance, and for
      episodes of streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis
      media. RESULTS: During the 6-month trial (N = 111 per group) the incidence of
      streptococcal pharyngo-tonsillitis, scarlet fever and acute otitis media was
      approximately 16%, 9% and 44% respectively in the treated group and 48%, 4% and
      80% in the control group. During the 3-months follow-up (N = 29 per group) the
      corresponding rates of infection were 15%, 0% and 12% in the treated group and
      26%, 6% and 36% in the controls. No apparent side effects were detected in the
      treated group either during treatment or follow-up. All of the enrolled children
      completed the study. CONCLUSIONS: The daily administration of BLIS K12 to
      children attending their first year of kindergarten was associated with a
      significant reduction in episodes of streptococcal pharyngitis and acute otitis
      media. No protection against scarlet fever was detected.

PMID- 27874936
TI  - Relationship between atrial fibrillation and heart failure.
AB  - Heart failure (HF) and atrial fibrillation (AF) are major health issues and often
      co-exist. HF and AF also share common mechanisms, as well as therapies and
      treatment strategies. The relationship between AF and HF has not been clarified
      and, therefore, remains an area of research interest. The choice of optimal
      treatment is a challenge for AF and HF. Control of rate or rhythm is the most
      important decision for physicians. New tactics for budgeting and centralized
      monitoring may have an exciting effect on stroke occurrence. Because it is
      predicted that AF or HF would markedly increase in the next two decades
      worldwide, a significant burden on the health care systems in multiple countries
      will occur. It remains imperative that further research about the epidemiology,
      mechanism, detection, and treatment of AF and HF is urgently promoted. In this
      paper, we review the recent progress on the relationship between HF and AF.

PMID- 27874937
TI  - Impact of complete and incomplete revascularization on short- and long-term
      quality of life in patients with multivessel coronary artery disease.
AB  - OBJECTIVE: In this study, we compared the impact of two main strategies of
      intervention against multivessel coronary disease (MVD), complete
      revascularization (CR) and incomplete revascularization (IR), on patients'
      quality of life. PATIENTS AND METHODS: 210 patients with multivessel disease were
      selected for this study. The diagnosis was confirmed by coronary angiography, and
      patients were divided in two different groups according to the type of
      revascularization method they received: (1) the complete revascularization (CR)
      group and (2) the incomplete revascularization (IR) group. Patients were asked to
      fill out SF-36 life quality questionnaire in three-time points: (1) before the
      operation; (2) one month after the operation; and (3) one year after the
      operation. RESULTS: Baseline conditions showed no significant intergroup
      differences. Scores obtained from different sections in the questionnaire were
      compared between two groups and results revealed that scores in every section
      were significantly different (p < 0.05) except for the general health condition
      section. Patients in the CR group scored higher in physical functioning, physical
      role, body pain, vitality, social role, emotional role and mental health. Scores
      obtained from different time points also varied significantly (p < 0.05), with
      those of one month and one year after operation being noticeably higher than the
      preoperative ones. CONCLUSIONS: Both complete and incomplete revascularization
      methods can effectively improve the short- and long-term quality of life in
      patients with multivessel coronary artery disease. However, complete
      revascularization can produce better results.

PMID- 27874938
TI  - RANK/RANKL/OPG pathway: genetic association with history of ischemic stroke in
      Italian population.
AB  - OBJECTIVE: RANKL is a member of the TNF superfamily that stimulates chemokine
      release, monocyte/macrophage matrix migration and matrix metalloproteinase
      activity and plays an important role in atherosclerosis. In our study, we have
      evaluated whether RANKL gene polymorphisms are involved in ischemic stroke in
      Italian subjects. PATIENTS AND METHODS: In a retrospective study we have included
      487 patients (242 males, 245 females) with history of ischemic stroke and 543
      control subjects without history of ischemic stroke (277 males, 276 females). The
      rs9533156, and rs2277438 gene polymorphisms of the RANKL gene were analyzed by
      PCR and restriction fragment length polymorphism. RESULTS: We found that the
      rs9533156 gene polymorphism of the RANKL gene was significantly (55.0% versus
      36.5%, p < 0.0001) and independently (adjusted OR 6.28 [2.34-4.21]) associated
      with history of ischemic stroke. No statistically significant difference was
      found between the two groups in our population for the rs2277438 gene
      polymorphism (p = 439). Furthermore, we have confirmed that rs 3134069, rs
      2073617 and rs 2073618 polymorphisms of the OPG gene were significantly and
      independently associated with cerebrovascular disorders. CONCLUSIONS: The present
      study identifies, for the first time, the genetic variant of RANKL as an
      independent risk factor for ischemic stroke.

PMID- 27874939
TI  - Health status correlates of malnutrition in the polish elderly population -
      Results of the Polsenior Study.
AB  - OBJECTIVE: The aim of the study was to analyze health-related factors associated
      with poor nutritional status (PNS) of a representative group of Polish older
      people, based on data from the PolSenior project (the first nation-wide study of
      Polish senior citizens). PATIENTS AND METHODS: Nutritional status was assessed in
      3751 community-dwelling older people (1770 females, mean age: 77.4+/-8.0 years)
      using the Mini Nutritional Assessment - Short Form. Elements of comprehensive
      geriatric assessment (cognitive and mood screening), selected medical data were
      analyzed in relation to the nutritional status. These were: the number of
      medications, the number of chronic diseases, selected diseases potentially
      related to malnutrition (anaemia, stroke, peptic ulcer, Parkinson's disease,
      cancer - past or present), total edentulism, use of dentures, and chronic pain.
      RESULTS: PNS was observed in 44.2% of participants. Female sex [OR 1.72, 95% Cl
      (1.45-2.04)], advanced age [OR 2.16 (1.80-2.58)], symptoms of depression [OR
      11.52 (9.24-14.38)], cognitive impairment [OR 1.52 (1.20-1.93], multimorbidity
      [OR 1.27 (1.04-1.57)], anaemia [OR 1.80 (1.41-2.29)] and total edentulism [OR
      1.26 (1.06-1.49)] were independently correlated with PNS. CONCLUSIONS: PNS in
      Polish elderly population is strongly related to the occurrence of symptoms of
      depression. People in advanced age with symptoms of depression, cognitive
      impairment, multimorbidity, anaemia and total edentulism should be screened and
      monitored for early symptoms of malnutrition.

PMID- 27874940
TI  - Hospital readmissions to internal medicine departments: a higher risk for
      females?
AB  - OBJECTIVE: Readmissions to hospital after discharge are considered adverse,
      serious and costly outcomes. In the last years, two new scores have been proposed
      to identify patients at high risk of hospital readmission, the HOSPITAL and the
      Elders Risk Assessment (ERA) indexes. The aim of this study was to evaluate these
      two scores and the risk of death among internal medicine readmitted patients.
      PATIENTS AND METHODS: During a 30-month period, we identified 613 readmitted
      patients out of 13,237 admissions. Age, sex, length-of-hospital stay (LOS), and
      deaths were retrospectively analyzed. Readmissions with diagnosis coincident with
      the index hospitalization were classified as avoidable, whilst those with a
      different diagnosis were defined as non-avoidable. HOSPITAL score for 30-day
      potentially avoidable readmission and ERA indexes were calculated. RESULTS:
      Readmitted patients (56.6% women), were aged 79+/-10.4 years. The incidence of 30
      day readmission was 20.4 patients/month. Re-hospitalization could be classified
      as avoidable in 286 cases (46.7%), and death at the end of follow-up was recorded
      in 366 (59.7%). HOSPITAL score >= 7 and ERA score >= 16, both able to identify
      high risk patients for readmission, were present in 108 (17.6%) and 385 (64.4%)
      of cases, respectively. Patients with non-avoidable readmissions were older, more
      frequently female, diabetic, and had higher ERA score than subjects with
      avoidable readmission. Multivariate logistic regression analysis showed that non
      avoidable readmissions were independently associated with female gender (OR 1.410
      [95% CI 1.012-1.964], p=0.042), and age (OR 1.025 [95% CI 1.006-1.043], p=0.01),
      while only age (OR 1.034 [95% CI 1.015-1.054], p<0.001) and ERA score (OR 1.047
      [95% CI 1.001-1.095], p=0.047) were independently associated with death at the
      end of follow-up. CONCLUSIONS: Although re-hospitalization represents frequent
      phenomenon related to age, non-avoidable readmissions mainly involve female
      patients. ERA score appears to be an useful practical tool, able to identify high
      risk patients.

PMID- 27874941
TI  - Gastroesophageal reflux disease. Are we acting in the best interest of our
      patients?
AB  - Oesophageal adenocarcinoma is strictly related to gastroesophageal reflux and
      cylindrical metaplasia of the epithelium of the distal esophagus (Barrett's
      esophagus) due to chronic inflammation. Worldwide incidence of oesophageal
      adenocarcinoma is rising despite the availability of precise international
      guidelines for the treatment of gastroesophageal reflux disease and the
      increasing use of proton-pump inhibitors (PPIs). While PPIs can control GERD
      symptoms in a significant amount of cases, still a large number of patients
      progress to Barrett's esophagus and adenocarcinoma. Recent investigations have
      demonstrated that in one-third of the patients their reflux symptoms are due to
      non-acid reflux, obviously not affected by PPIs. Robust evidences are available
      to demonstrate the role of non-acid reflux in the development of Barrett's
      esophagus and adenocarcinoma. Therefore, PPIs are not effective in preventing the
      worst complications of GERD. It is mandatory to develop new and more effective
      guidelines on the treatment of GERD; that would take into account the fact that
      GERD should be considered a "surgical" disease, as it is due, at least in its
      late stages, to an anatomical defect of the lower oesophageal sphincter. Medical
      treatment should be considered in early stage GERD, when reflux is due to
      transient relaxations of the lower oesophageal sphincter, whereas surgery should
      be considered in late stages, in the presence of a demonstrated mechanical
      failure of the sphincter.

PMID- 27874942
TI  - Breathing training on lower esophageal sphincter as a complementary treatment of
      gastroesophageal reflux disease (GERD): a systematic review.
AB  - OBJECTIVE: Gastroesophageal reflux disease (GERD) represents one of the most
      common gastrointestinal disorders, but is still a challenge to cure. Proton pump
      inhibitors (PPIs) are currently the GERD's standard treatment, although not
      successful in all patients; some concerns have been raised regarding their long
      term consumption. Recently, some studies showed the benefits of inspiratory
      muscle training in increasing the lower esophageal sphincter pressure in patients
      affected by GERD, thereby reducing their symptoms. MATERIALS AND METHODS:
      Relevant published studies were searched in Pubmed, Google Scholar, Ovid or
      Medical Subject Headings using the following keywords: "GERD" and physiotherapy",
      "GERD" and "exercise", "GERD" and "breathing", "GERD and "training". RESULTS: At
      the end of our selection process, four publications have been included for
      systematic review. All of them were prospective controlled studies, mainly based
      on the training of the diaphragm muscle. GERD symptoms, pH-manometry values and
      PPIs usage were assessed. CONCLUSIONS: Among the non-surgical, non
      pharmacological treatment modalities, the breathing training on diaphragm could
      play an important role in selected patients to manage the symptoms of GERD.

PMID- 27874943
TI  - MR-enterography with diffusion weighted imaging: ADC values in normal and
      pathological bowel loops, a possible threshold ADC value to differentiate active
      from inactive Crohn's disease.
AB  - OBJECTIVE: The aim of our study was to compare the apparent diffusion coefficient
      (ADC) values of pathological bowel loops wall (pADC) with the ADC values of
      normal appearing ones (naADC) and to determine a discriminating threshold.
      PATIENTS AND METHODS: 60 patients were studied at our Institution through a MR
      enterography that included free-breathing axial Diffusion Weighted Imaging (DWI)
      with two b (0 and 800 s/mm2) after histological diagnosis of active Crohn's
      disease (CD). The one (when unique) or the best analyzable (when multiple)
      pathological bowel loop was identified in each patient, on the basis of the MRI
      features: wall thickness, presence of mural oedema and wall contrast enhancement
      after contrast medium administration. A normal appearing bowel loop was used for
      comparison. ADC values were measured in consensus by two radiologists, and they
      were compared with t-test. The ADC threshold value for the differentiation
      between pathological and normal appearing bowel loops was determined. RESULTS:
      The pADC values were significantly lower than the naADC values (1.48 +/- 0.058 x
      10-3 mm2/s versus 3.525 +/- 0.07 x 10-3 mm2/s; p < 0.05). A threshold of 2.416 x
      10-3 mm2/s showed 100% sensitivity and 100% specificity for the discrimination
      between normal and pathological bowel loops. CONCLUSIONS: In patients with active
      CD the ADC values of the pathological bowel wall are significantly lower than
      those of normal appearing bowel loops. A threshold of ADC value of 2.416 10-3
      mm2/s could discriminate normal from pathological bowel loops.

PMID- 27874944
TI  - Rupture of liver abscess following hepatogastric fistula caused by perforation of
      remnant gastric carcinoma: a case report.
AB  - OBJECTIVE: We report the case of a 73-year-old man, with a history of proximal
      subtotal gastrectomy, who suffered acute abdominal symptoms and signs. Laparotomy
      showed rupture of liver abscess and hepatogastric fistula formation caused by
      perforation of remnant stomach. CASE REPORT: Residual stomach resection, incision
      and drainage of liver abscess were performed, and the patient was smoothly
      discharged from hospital nineteen days after the emergency operation. RESULTS:
      The final pathology confirmed the remnant gastric adenocarcinoma. This case is so
      far the first reported liver abscess caused by perforation of residual stomach
      malignant tumor. CONCLUSIONS: Liver abscess and hepatogastric fistula are rare.
      This is the first report on a remnant gastric adenocarcinoma (RGC) invading the
      adjacent liver, with ruptured liver abscess resulting from gastric perforation.
      We speculated that there were inevitable factors for this case. Direct invasion
      to the liver capsule of gastric carcinoma was the bridging basic of the formation
      of a hepatogastric fistula. Pyloric obstruction caused by gastric carcinoma was
      the driver of liver abscess rupture since the increased proximal gastrointestinal
      pressure led to the inner pressure of liver abscess rising through the conduction
      of hepatogastric fistula. The recommended treatment protocol for this clinical
      entity comprises removal of the primary lesions and drainage of the liver
      abscess. This successful case provided us with a great deal of clinical
      information and treatment experience.

PMID- 27874945
TI  - Clinical effects in resection of congenital choledochal cyst of children and
      jejunum Roux-Y anastomosis by laparoscope.
AB  - OBJECTIVE: We compared the effects and complications in resection of the
      congenital choledochal cyst (CCC) and hepatic duct jejunum Roux-Y anastomosis by
      laparoscopy and open surgery. PATIENTS AND METHODS: We continuously selected 156
      cases of pediatric patients with CCC, which were divided into 70 cases of the
      laparoscopic group and 86 cases of laparotomy group according to the treatment
      methods. Then the success rate of surgery, intraoperative and postoperative
      bleeding, intraoperative and postoperative complications was compared. RESULTS:
      It was found that after 65 cases (92.9%) completed in the laparoscopic group and
      all completed in laparotomy group there was less intra-operative blood loss of
      laparoscopic group than that of the open surgery group. However, the difference
      of postoperative hemorrhage in two groups was not statistically significant (p
      >0.05). The intra-operative complications in the two groups were not
      significantly different (p >0.05); in the laparoscopic group, the postoperative
      complication rate was significantly lower than open surgery group (p <0.05).
      CONCLUSIONS: Laparoscopic resection of CCC combined with jejunum Roux-Y
      anastomosis has good prospects.

PMID- 27874946
TI  - Visual and somotosensory evoked potentials in asymptomatic patients with vitamin
      B12 deficiency.
AB  - OBJECTIVE: Vitamin B12 deficiency may be asymptomatic or present with a wide
      range of neurological and hematological disorders. Our aim in this study is to
      evaluate visual (VEP) and somatosensory evoked potential (SEP) parameters in
      patients with vitamin B12 deficiency who had no clinical evidence of visual
      impairment or neurological syndrome findings and compare the findings with
      healthy controls to determine whether there is a correlation between VEP and SEP
      parameters and serum vitamin B12 levels. PATIENTS AND METHODS: 30 patients (6
      females [20%], 24 males [80%]; mean age, 52 years [range 17-80 years]), and 15
      healthy subjects with vitamin B12 deficiency (3 females [20%], 12 [80%] male;
      mean age, 49 years [range 17-78 years]) were included in the study. P100 wave
      latencies and amplitudes were recorded as VEP parameters, and P40 wave latencies
      and amplitudes were recorded as tibial SEP parameters. RESULTS: Comparison of VEP
      and SEP parameters in the patient and control groups revealed significantly
      prolonged SEP latencies and lower SEP amplitudes in the patient group. VEP
      latencies did not significantly differ between the patient and the control groups
      while VEP amplitudes were found to be lower in the patient group than in
      controls. A significant correlation was obtained between serum vitamin B12 levels
      and tibial SEP latencies (r > 0.5). CONCLUSIONS: These findings suggest that
      asymptomatic patients with vitamin B12 deficiency may have SEP and VEP
      abnormalities indicating the subclinical optic nerve and spinal cord involvement.

PMID- 27874947
TI  - The relationship between the occurrence of intractable epilepsy with glial cells
      and myelin sheath - an experimental study.
AB  - OBJECTIVE: The occurrence of epilepsy is associated with myelin sheath injury;
      oligodendrocyte (OL) is the main cell of myelin sheath; In this study, we
      observed the changes of OL, demyelination, and myelin associated protein in
      different stages of intractable epilepsy (IE) at the epileptic foci of patients,
      and provide useful information for the pathophysiology of IE. PATIENTS AND
      METHODS: IE patients who received epileptogenic focus resection were recruited as
      the experimental group, their medical records were collected and postoperative
      follow-up was performed. The brain tissues from10 cases with non-brain disorders
      were obtained as controls. Immunofluorescence double staining was used to observe
      OL expression. The demyelination in epileptic foci was observed by luxol fast
      blue (LFB) staining method. Real-time fluorescent quantitative (RT) PCR, Western
      blot methods were used to detect the expressions of myelin-related proteins.
      RESULTS: We observed increased OL precursor cells, former OL and decreased mature
      OL in experimental group when compared with controls (both p < 0.05). The
      demyelination was obviously higher in experimental group when compared with
      controls (p < 0.01). We also observed significantly decreasing of myelin basic
      protein (MBP), oligodendrocytes myelin glycoprotein (OMgp), myelin associated
      glycoprotein (MAG) and other MAG associated proteins-Nogo receptors (NgRs) and
      GD1alpha (p < 0.01) in epileptic foci. CONCLUSIONS: OL is differentiated
      abnormally at epileptic foci of patients with IE; the demyelination, decreasing
      of demyelination and myelin associated protein are related to the occurrence of
      IE.

PMID- 27874948
TI  - Epicardial fat thickness is associated with severity of disease in patients with
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: Cardiovascular diseases (CVD) are common in patients with chronic
      obstructive pulmonary disease (COPD) and the BODE index is an important tool for
      the prognostic assessment of COPD patients. It is well known that epicardial fat
      thickness (EFT) is related to CVD. However, there are very few data about the
      relationship between EFT and BODE index. The aim of this study is to investigate
      the relationship between EFT and BODE index in patients with COPD. PATIENTS AND
      METHODS: We prospectively included 157 patients with COPD and 45 controls in the
      present study. All patients underwent pulmonary function tests and six-minute
      walking test. EFT and other echocardiographic parameters were measured using
      transthoracic echocardiography on admission. Patients were divided into four
      quartiles according to the BODE index scores (Quartile-1 (Q1): 0-2 points;
      Quartile-2 (Q2): 3-4 points; Quartile-3 (Q3): 5-6 points; Quartile-4 (Q4): 7-10
      points). High sensitive C-reactive protein (Hs-CRP) and other biochemical
      parameters were measured in all participants. RESULTS: COPD patients had higher
      EFT values compared with control group (p<0.05). When COPD patients were
      classified according to BODE index quartiles, the highest EFT values were
      observed in Q1 compared with other quartiles (p<0.05, for all). EFT values showed
      a decreasing trend from Q1 to Q4. Furthermore, EFT was independently associated
      with BODE index (beta=0.405, p<0.001), Hs-CRP (beta=0.300, p<0.001) and diabetes
      (beta=0.338, p<0.001) in multivariate linear regression analysis. CONCLUSIONS:
      Our findings suggested that EFT is independently and negatively associated with
      the severity of disease as indicated by BODE index in patients with COPD.

PMID- 27874949
TI  - miR-377 inhibited tumorous behaviors of non-small cell lung cancer through
      directly targeting CDK6.
AB  - OBJECTIVE: This study is aimed to investigate the cellular role of miR-377 and
      demonstrate that miR-377 negatively regulated cyclin-dependent kinase 6(CDK6) in
      human non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: qRT-PCR
      was performed to identify the miR-377 expression level in 45 paired NSCLC and
      adjacent normal lung tissues. Cell proliferation was measured by MTT. Apoptosis
      was detected by flow cytometric analysis. Luciferase reporter assays were
      employed to validate regulation of a putative target of miR-377. The effect of
      miR-377 on endogenous levels of this target was subsequently confirmed via
      Western blot. RESULTS: We found that the expression level of miR-377 was
      significantly reduced in NSCLC tissues and cell lines. On the contrary, CDK6
      expression level was up-regulated in NSCLC tissues and cell lines. Based on
      Luciferase reporter assays, we confirmed that CDK6 was a direct target gene of
      miR-377. In vitro studies demonstrated that miR-377 overexpression reduced NSCLC
      cell proliferation and promoted apoptosis. CONCLUSIONS: Our discovery suggested
      that miR-377 might be used as a therapeutic reagent for the treatment of NSCLC in
      the future.

PMID- 27874951
TI  - High expression of long noncoding RNA Sox2ot is associated with the aggressive
      progression and poor outcome of gastric cancer.
AB  - OBJECTIVE: The aim of our study was to investigate the expression of long non
      coding RNA Sox2ot (Sox2ot) in gastric cancer (GC) patients and its association
      with clinicopathologic parameters and the prognosis. PATIENTS AND METHODS:
      Quantitative real-time polymerase chain reaction was performed to detect Sox2ot
      expression in 155 GC tissues and paired adjacent normal tissues. The
      relationships between Sox2ot expression and the clinicopathological features of
      GC patients were analyzed. Furthermore, overall survival (OS) and disease-free
      survival (DFS) were evaluated using the Kaplan-Meier method, and multivariate
      analysis was performed using the Cox proportional hazard analysis. RESULTS:
      Sox2ot expression levels were decreased in cancerous tissues compared to their
      corresponding non-cancerous controls (p < 0.01). Sox2ot expression was associated
      with T stage, distant metastasis and differentiation (p = 0.009, 0.034 and 0.001,
      respectively). In addition, patients with high Sox2ot expression tended to have
      poorer OS and DFS (p < 0.001, respectively). Finally, multivariate analysis
      showed Sox2ot expression was an independent prognostic factor for GC patients.
      CONCLUSIONS: Our findings showed that overexpressed Sox2ot was correlated with
      aggressive tumor behavior. Sox2ot may serve as a novel prognostic factor and a
      potential target to improve the long-term outcome of GC.

PMID- 27874950
TI  - miR-194 inhibits gastric cancer cell proliferation and tumorigenesis by targeting
      KDM5B.
AB  - OBJECTIVE: MicroRNAs play critical roles in regulating gene expression and
      various cellular processes in human cancer malignant progression. The aim of the
      present study was to examine the expression pattern of miR-194 in gastric cancer
      (GC) and its biological role in tumor progression. MATERIALS AND METHODS: Using
      quantitative RT-PCR, we detected miR-194 expression in GC cell lines and primary
      tumor tissues. The proliferation, migration, and invasion assays were performed
      to investigate the effect of miR-194 on the GC cells. The target of miR-194 was
      predicted by TargetScan and confirmed by luciferase reporter assay. KDM5B
      expression was detected by Western blot. RESULTS: miR-194 was significantly down
      regulated in GC tissues and cell lines. Over-expression of miRNA-194 could
      inhibit GC cell proliferation, migration, and invasion in vitro. Also, miR-194
      inhibited tumor growth and progression in vivo. Dual luciferase-based reporter
      assay indicated direct regulation of KDM5B by miR-194. CONCLUSIONS: Our findings
      suggested that miR-194 directly targeted KDM5B and thereby acted as a tumor
      promoter in GC progression.

PMID- 27874952
TI  - Nox1 promotes colon cancer cell metastasis via activation of the ADAM17 pathway.
AB  - OBJECTIVE: Reactive oxygen species (ROS) generated by endogenous metabolic
      enzymes are involved in a variety of pathology processes, including cancer. In
      particular, superoxide-generating NADPH oxidase 1 (Nox1), a member of Nox enzyme
      family, is highly expressed in the colon tissue and has been implicated in
      physiological and pathophysiological states of colon cancer. However, the
      underlying molecular mechanism of Nox1 in the regulation of colon cancer
      progression remains largely unknown. MATERIALS AND METHODS: In vitro scratch
      wound healing and invasion assays were used to compare the migration and invasion
      abilities of HT29 cells in which Nox1 protein levels were manipulated. Western
      blot assay was performed to detect the expression of key proteins of the EGFR
      PI3K-AKT signaling pathway. Immunoprecipitation assay was performed to detect the
      interaction between Nox1 and ADAM17. RESULTS: Nox1 overexpression promoted colon
      cancer cell growth, migration, and invasion through the EGFR-PI3K-AKT signaling
      pathway. At the molecular level, Nox1 regulated the expression of tumor necrosis
      factor-alpha (TNF-alpha) converting enzyme (TACE)/a disintegrin and
      metalloprotease domain 17 (ADAM17). Furthermore, Nox1 interacted with and
      stabilized ADAM17 from ubiquitin-mediated degradation, leading to the activation
      of the ADAM17 signaling pathway. CONCLUSIONS: This study suggests that Nox1
      promotes colorectal cancer metastasis by modulating the stability of ADAM17.

PMID- 27874953
TI  - The expression of B7-H3 and B7-H4 in human gallbladder carcinoma and their
      clinical implications.
AB  - OBJECTIVE: To investigate the expression of B7-H3 and B7-H4 and their clinical
      implications in human gallbladder carcinoma. PATIENTS AND METHODS: The expression
      of B7-H3 and B7-H4 in the 252 samples (126 cases of chronic cholecystitis and 126
      cases of gallbladder cancer) was detected by the streptavidin-peroxidase
      immunohistochemical method, and their associations with tumor classification,
      clinical grade, and recurrence were assessed. RESULTS: In chronic cholecystitis
      tissue, B7-H3 and B7-H4 were not detected. In 126 cases of gallbladder carcinoma,
      the positive rates of B7-H3 and B7-H4 expression were 66.67% and 69.05%
      respectively (p < 0.05). The positive rate of B7-H3 in the primary-onset group
      was 53.57%, and that in recurrence group was 92.86% (p < 0.05). The positive rate
      of B7-H4 in the primary-onset group was 85.19%, and that in recurrence group was
      40.00% (p < 0.05). Expression of B7-H3 was consistent with B7-H4 expression in
      gallbladder carcinoma. CONCLUSIONS: B7-H3 and B7-H4 were up-regulated in
      gallbladder cancer; the high expression of B7-H3 may contribute to the early
      diagnosis of gallbladder carcinoma and the assessment of postoperative survival
      and recurrence. B7-H4 may play an important role in the incidence of gallbladder
      cancer. B7-H3 and B7-H4 may play a synergetic role in gallbladder carcinoma.
      Combined tests were available for the diagnosis, degree assessment and prognosis
      of gallbladder carcinoma, which may be a new target for molecular targeted
      therapy of gallbladder carcinoma.

PMID- 27874954
TI  - The anti-cancer effects of cisplatin on hepatic cancer are associated with
      modulation of miRNA-21 and miRNA-122 expression.
AB  - OBJECTIVE: Cisplatin is an effective chemotherapeutic drug to treat hepatic
      cancer, but its efficacy is marred by extensive adverse effects. Micro (mi) RNAs
      are small regulatory RNAs that may be used as molecular targets to better fine
      tune chemotherapy in hepatic cancer. In this study, we examined to what extent
      the anti-cancer effects of cisplatin are associated with expressions of miRNA
      (miR)-21 and miR-122. MATERIALS AND METHODS: The growth-inhibiting effects of
      cisplatin on the human hepatic cell line HepG2 were assessed by MTT assay, while
      cell apoptosis was documented using DAPI staining. Also, we tested the effects of
      cisplatin on tumour growth in a mouse tumour xenograft model. Finally, we
      quantified expression levels of miR-21 and miR-122 in cisplatin-treated HepG2
      cells. RESULTS: We observed that cisplatin significantly decreased the growth of
      HepG2 cells (p < 0.05 vs control cells) at all tested concentration (5-80 ug/ml)
      after 24 or 48 hours of treatment. Microscopic studies demonstrated apoptotic
      signs in cisplatin-treated cells. In the mouse tumour xenograft model, tumour
      weights and volumes were significantly (p < 0.05 untreated animals) lower after
      treatment with cisplatin. Also, treatment of HepG2 cells for 48 hours with 20
      ug/ml cisplatin was associated with significant decreases in miR-21 expression
      levels and up-regulation of miR-122. CONCLUSIONS: The anti-cancer effects of
      cisplatin are associated with down-regulation of miR-21 expression and up
      regulation of miR-122.

PMID- 27874955
TI  - Expression and significances of MiRNA Let-7 and HMGA2 in laryngeal carcinoma.
AB  - OBJECTIVE: High mobility group protein A2 (HMGA2) is a reported new oncogene been
      regulated by tumor suppressor microRNA Let-7. HMGA2 has become a hot topic in
      fundamental and clinical research of laryngeal carcinoma. The aim of the current
      study is to investigate the molecular mechanism of Let-7 and HMGA2 in oncogenesis
      and progression of laryngeal cancer. PATIENTS AND METHODS: We used quantitative
      RT-PCR to detect the expression of miRNA Let-7a and HMGA2 mRNA from 59 pairs of
      fresh laryngeal cancer tissues and adjacent tissues collected for the laryngeal
      cancer patient. The expression of HMGA2 protein was detected by western blot
      method. RESULTS: There is a negative correlation between low expressed miRNA Let
      7a and high expression of HMGA2 mRNA in human laryngeal cancer (p < 0.05). The
      expressions of miRNA Let-7a and HMGA2 have a significant difference in patients
      with clinical stage I-II and clinical stage III-IV, patients with well
      differentiated tumor and patients with poorly differentiated tumor, patients with
      lymph node metastasis and patients without lymph node metastasis. Spearman
      correlation analysis of miRNA Let-7a and HMGA2 mRNA showed expression of miRNA
      Let-7a is negatively correlated with HMGA2 expression. CONCLUSIONS: The down
      regulation of miRNA Let-7a and up-regulation of HMGA2 promote the invasion and
      metastasis of laryngeal cancer.

PMID- 27874956
TI  - Up-regulation of long non-coding RNA BCAR4 predicts a poor prognosis in patients
      with osteosarcoma, and promotes cell invasion and metastasis.
AB  - OBJECTIVE: The long non-coding RNA BCAR4 (BCAR4) has been reported to be
      associated with cancer development. The aim of our study was to investigate the
      expression of BCAR4 in osteosarcoma patients and its association with
      clinicopathologic parameters and the prognosis. PATIENTS AND METHODS:
      Quantitative RT-PCR (qRT-PCR) assay was used to detect the expression of BCAR4
      and its correlations with clinicopathological factors were statistically
      analyzed. The clinical and prognostic significance of BCAR4 expression was
      analyzed statistically by Kaplan-Meier estimate and Cox regression model.
      Furthermore, Cell proliferation, migration, and invasion were evaluated using
      counting assay Kit-8 (CCK-8) and transwell assay, respectively. RESULTS: We found
      that BCAR4 expression was higher in osteosarcoma tissues and cell lines than that
      in normal controls. The BCAR4 levels were significantly correlated with clinical
      stage and distant metastasis. Kaplan-Meier analysis with the log-rank test
      indicated that high expression of BCAR4 had a decreased overall survival (OS).
      Univariate and multivariate analyses showed that BCAR4 expression was an
      independent predictor of overall survival. Furthermore, decreased expression of
      BCAR4 markedly inhibited osteosarcoma cell proliferation, migration, and
      invasion. CONCLUSIONS: The results of the present study identified a crucial
      tumor promotive role of BCAR4 in the progression of osteosarcoma, and suggested
      that BCAR4 may be a potential therapeutic agent for the treatment of
      osteosarcoma.

PMID- 27874957
TI  - Restoration of microRNA-373 suppresses growth of human T-cell lymphoma cells by
      repressing CCND1.
AB  - OBJECTIVE: Adult T cell lymphoma is a highly aggressive T-cell malignancy. This
      study was designed to explore the expression and functional significance of
      microRNA (miR)-373 in T cell lymphoma. PATIENTS AND METHODS: We analyzed the
      levels of CCND1 and miR-373 in T cell lymphoma tissue and the relationship of miR
      373 levels with patients' prognosis. We then overexpressed miR-373 by miRNA
      mimics transfection and inhibited miR-373 by miRNA antisense transfection in T
      cell lymphoma cells. Cell survival and growth were analyzed by CCK-8 assay and
      MTT assay, respectively. Cell proliferation was analyzed by flow cytometry.
      Bioinformatics analyses were applied to predict miR-373 targets, which were then
      confirmed by luciferase reporter assay. RESULTS: We detected significantly higher
      levels of CCND1, and significantly lower levels of miR-373 in T cell lymphoma
      tissue, compared to the adjacent non-tumor tissue. Moreover, the low miR-373
      levels were associated with poor survival of the patients. Overexpression of miR
      373 significantly inhibited cell growth, while depletion of miR-373 increased
      cell growth in T cell lymphoma cells. Moreover, the effects of miR-373 on cell
      growth appeared to result from an alteration in cell proliferation. Finally, miR
      373 was found to bind to the 3'-UTR of CCND1 mRNA to inhibit its translation in T
      cell lymphoma cells. CONCLUSIONS: Our study suggests that reduced miR-373 levels
      in T cell lymphoma tissue may promote T cell lymphoma growth, possibly through
      CCND1-mediated cell proliferation.

PMID- 27874959
TI  - New lift: the art of facial rejuvenation with minimal incisions rhytidectomy.
AB  - OBJECTIVE: The new lift is a procedure for facial rejuvenation with minimal
      incision, giving the patient a significant improvement of mid face and neck, with
      limited dissection and minimal scars. A further "One-stitch" of anchorage to the
      deep temporal fascia is required to hold tissues. By a minimal surgical access,
      we get a suitable cheek lift with the improvement of nose-labial folds,
      mandibular edge and neck contour. PATIENTS AND METHODS: Between February 2009 and
      June 2012, 32 patients underwent facial rejuvenation surgery called new lift at a
      mean age of 46 years (range 35-55 years). Seven of the patients had a previous
      facelift. 12 out of 32 patients (37.5%) had concomitant eyelid surgery and 4
      (12.5%) neck contouring procedure. RESULTS: The technique we used is a safe and
      effective procedure with a high satisfaction rate; 28 patients (89%) were very
      satisfied with their result at 24-months follow-up. CONCLUSIONS: The surgical
      outcome was evaluated according to the analysis of photographs obtained before
      and after surgery and the analysis of pre- and postoperative measurements.
      Aesthetic results were evaluated also by patients themselves who indicated a high
      satisfaction rate at three months post-surgery questionary and by a surgeon not
      involved in the study using VAS (1-10) before and three months after surgery.
      Acquired data on the aesthetic result were statistically evaluated using Student
      t-test. This is a study aimed at assessing the effectiveness of the new-lift
      technique for facial rejuvenation. Based on the results of our study, the new
      lift is a very effective surgery for rejuvenation of the face with mild to
      moderate aging. All patients healed uneventfully without any major postoperative
      problems. This technique responds to an increasing demand from a wide range of
      patients for less invasive, less expensive operations with faster healing time
      and fewer potential complications.

PMID- 27874958
TI  - Diagnostic accuracy of MDCT in the evaluation of patients with peritoneal
      carcinomatosis from ovarian cancer: is delayed enhanced phase really effective?
AB  - OBJECTIVE: To assess the diagnostic accuracy of delayed enhanced phase in
      addition to portal enhanced phase in MDCT imaging for depicting peritoneal
      carcinomatosis (PC) implants in patients with ovarian cancer. PATIENTS AND
      METHODS: We retrospectively reviewed double-phase, portal enhanced phase (PEP)
      and delayed enhanced phase (DEP), MDCT-examinations of 40 patients with clinical
      suspicion of recurrent PC from histopathologically-proven ovarian cancer,
      previously treated with both cytoreductive surgery and adjuvant/neoadjuvant
      chemotherapy. Image assessment was performed by three independent blinded readers
      (2 experienced and 1 less-experienced radiologists) in 3 different reading
      sessions: PEP (set A), DEP (set B), and PVP + DEP (set C). All CT-images were
      qualitatively assessed on the basis of the location of the lesion (based on
      Sugarbaker scheme), presence (indicating a confidence level for the diagnosis of
      PC), size and pattern. Reference standard both for detection and exclusion of PC
      was the evaluation of double-phase MDCT exams performed by two experienced
      readers in consensus, knowing clinical and laboratoristic parameters as well as
      previous and subsequent imaging (follow-up minimum of 12 months). Sensitivity,
      specificity, PPV, NPV and diagnostic accuracy of each reader for each reading
      session were calculated and compared. A subgroup analysis based on lesion pattern
      was also performed. RESULTS: On a total of 507 abdominal-pelvic sites evaluated,
      PC was found in 182 regions (35.9%). When considering experienced radiologists,
      no statistically significant differences (p>0.05) were found between the
      different sets of images. The analysis by less-experienced radiologist showed
      lower statistical results, which significantly improved when both PEP and DEP
      were evaluated. In the subgroup analysis, DEP showed significantly higher
      statistical results in the case of micronodular patterns. CONCLUSIONS: Our
      results indicate that the CT-acquisition protocol in patients with ovarian cancer
      for tumor staging should be based on portal phase alone, with a significant
      radiation dose reduction, whereas the addition of delayed phase images is useful
      for less-experienced readers.

PMID- 27874960
TI  - Surgical therapy of breast hypertrophy: a comparison of complications and
      satisfaction rate in large and small superior pedicle custom-made reduction
      mammaplasty.
AB  - OBJECTIVE: The reduction mammaplasty is indicated for patients with symptomatic
      breast hypertrophy. Although surgery is considered the gold standard treatment,
      it is still debated which is the complication rate and whether or not there is an
      increased complication rate with increased tissue resection per breast. The main
      objective of this retrospective study was to determine whether the rates of
      complications are higher in large reductions (>=2000 g per breast) as compared
      with smaller reductions (<=1999 g per breast) using the superior pedicle custom
      made technique. PATIENTS AND METHODS: A retrospective study of 90 consecutive
      operated patients was performed. All the patients underwent a bilateral breast
      reduction for macromastia. 43 patients had a reduction of 1999 g or less and 47
      patients had a reduction of 2000 g or more. RESULTS: There were no statistically
      significant differences in the rates of nipple necrosis, hematoma, seroma, wound
      dehiscence, wound infection, loss or reduction of nipple sensation, and a
      pathologic scar between the large and small resections. CONCLUSIONS: The large
      reduction patients pointed higher mean satisfaction rate than the small reduction
      patients. The superior pedicle custom-made technique is a safe method of breast
      reduction regardless of the degree of parenchymal resection, achieving a
      successful aesthetic outcome with minimal scarring and high satisfaction rate for
      both small and large breast reduction.

PMID- 27874961
TI  - Letter to the Editor - miR-494 inhibits invasion and proliferation of gastric
      cancer by targeting IGF-1R.

PMID- 27874962
TI  - Analysis of risk factors of type a aortic dissection (TAAD) operation of frozen
      elephant trunk and total arch replacement.
AB  - OBJECTIVE: To investigate the incidence and risk factors of acute renal failure
      (ARF) after operation of frozen elephant trunk and total arch replacement for
      acute thoracic aortic aneurysm and dissection (TAAD) with mild hypothermic
      circulatory arrest (MHCA), and to analyze the long-term survival rate of the
      patients with ARF. PATIENTS AND METHODS: From February 2009 to March 2015,
      patients with acute TAAD accepted operation of frozen elephant trunk and total
      arch replacement were enrolled. Those patients who were treated with renal
      replacement treatment (RRT) before the operation were excluded. The age, gender,
      cardiovascular disease history, preoperative serum creatinine and extracorporeal
      circulation duration in operation were recorded. On the basis of requiring RRT
      after TAAD operation, the patients were divided into ARF group and non-ARF group.
      The risk factors of ARF after TAAD operation were assessed by univariate and
      multivariate analysis. After completion of clinical follow-up, Kaplan-Meier curve
      was drawn to analyze five-year survival. RESULTS: A total of 524 patients were
      included in the study. 51 cases of them got postoperative ARF. The incidence was
      9.7%. The mortality rate of ARF group in the hospital was significantly higher
      than non-ARF group (25.5% vs. 3.6%; p<0.001). Univariate analysis showed that
      there was statistically significant difference in the age, gender, hypertension
      history, preoperative serum creatinine >=200 umol/L, extracorporeal circulation
      duration >=260 min and combined with coronary artery bypass surgery
      simultaneously (p<0.05). Multiple logistic regression analysis showed that there
      were three independent risk factors of ARF after the operation, including
      hypertension (p=0.031, OR=2.377), preoperative serum creatinine >=200 umol/L
      (p=0.005, OR=4.451) and extracorporeal circulation duration >=260 min (p=0.002,
      OR=3.295). The total five-year survival rate of ARF group after the operation was
      56%. There was no statistically significant difference in the five-year survival
      rate between preoperative serum creatinine >=200 umol/L group and <200 umol/L
      group (p>0.05). CONCLUSIONS: The incidence of ARF after the operation was 9.7%.
      Preoperative serum creatinine >=200 umol/L, hypertension history and
      extracorporeal circulation duration >=260 min were independent risk factors of
      ARF after the operation. The five-year survival rate of ARF after the operation
      was 56%. The preoperative serum creatinine level had no influence on the
      postoperative long-term survival.

PMID- 27874963
TI  - Study on the functions and mechanism of immune functions of human telomerase
      reverse transcriptase regulating dendritic cells treating sepsis.
AB  - OBJECTIVE: We analyzed the functions and mechanisms of immune functions of human
      telomerase reverse transcriptase regulating dendritic cells (DC) treating sepsis
      of mice models. MATERIALS AND METHODS: Eighty clean grade Balb/c animals aged
      from 6 to 8 weeks, weighted from 18 g to 22 g were selected for this study. The
      DC cells were harvested from the animals and cultivated to transfect with the
      recombinant eukaryotic expression plasmid hTERT-IRES2-EGFP construct. The LPS (E.
      coli 0111:B4, 5 mg/kg) was injected into the abdominal cavity of mice to
      establish sepsis models. Afterwards, animals were divided randomly into the
      sepsis group (A group), the group of hTERT transfecting DC (B group), the group
      of DC un-transfected (C group) with 25 mice in each group. 5 mice were in the
      normal control group (D group), without any treatment. An equivalent volume of
      normal saline was injected into the abdominal cavity of A group. Subsequently, 1
      ml of cell suspension (105/ml) was transfected into B and C groups respectively.
      Five animals from A, B, C groups and one animal from group D were sacrificed
      after 24h, 48h, 72d, 7d and 10d respectively. RESULTS: It was found that median
      survival time of the group of hTERT transfecting DC was remarkably higher than
      that of the untransfected group and the sepsis group. The average scores of the
      pathology of kidney and intestine at each time were significantly lower than that
      of the other two groups (p<0.05). At each time point, in the group of hTERT
      transfecting DC, levels of CRP and Cr were remarkably lower than that of the
      other two groups; HLA-DR, CD40 of immune phenotype and the expression level of
      peripheral blood T cells MHC-II molecules were significantly higher than that of
      the other two groups; the expression level of IL-12 and TNF-a were significantly
      lower than that of the other two groups; apoptosis rate of DC were significantly
      lower than that of the other two groups; the content and activity of NF-kappaB
      were significantly higher than that of the other two groups (p<0.05).
      CONCLUSIONS: The telomerase reverse transcriptase gene can raise the expression
      and maturity of DC, reduce apoptosis, induce cytokine secretion, reduce the
      inflammatory response and increase the survival time.

PMID- 27874964
TI  - Kinetics of volatile marker compounds during ripening of cured loins inoculated
      with Staphylococcus carnosus.
AB  - BACKGROUND: The current study was designed to investigate the influence of
      ripening time (12 weeks, 15  degrees C) on the volatile compounds and sensory
      acceptance for North European cured loins inoculated with a proteolytic
      Staphylococcus carnosus starter culture. RESULTS: The results demonstrated that
      the trend of volatile compounds, sensory acceptance and proteolytic activity
      increased during a ripening of 7 to 9 weeks. A further ripening led to a plateau
      phase for sensory attributes and aroma-relevant volatile compounds such as
      benzaldehyde, nonanone and acetophenone. The inoculation of the proteolytic S.
      carnosus LTH 3838 significantly increased aroma-relevant volatile compounds (3
      methylbutanal, benzaldehyde, acetophenone, 1-octen-3-ol) and sensory acceptance
      up to a score 3.5 and 3.6 for the overall odour and taste by week 9. In addition,
      compounds such as nonanal, hexanal, 2-pentanone and nonanone, which originate
      from lipid oxidation, were significantly limited by S. carnosus LTH 3838.
      CONCLUSION: A ripening time of 7 to 9 weeks seems to be an optimal period for the
      production of aroma intensive smoked North European cured loins. (c) 2016 Society
      of Chemical Industry.

PMID- 27874965
TI  - Somatostatin Agonist Pasireotide Inhibits Exercise-Stimulated Growth in the Male
      Siberian Hamster (Phodopus sungorus).
AB  - The Siberian hamster (Phodopus sungorus) is a seasonal mammal, exhibiting a suite
      of physiologically and behaviourally distinct traits dependent on the time of
      year and governed by changes in perceived day length (photoperiod). These
      attributes include significant weight loss, reduced food intake, gonadal atrophy
      and pelage change with short-day photoperiod as in winter. The central mechanisms
      driving seasonal phenotype change during winter are mediated by a reduced
      availability of hypothalamic triiodothyronine (T3), although the downstream
      mechanisms responsible for physiological and behavioural changes are yet to be
      fully clarified. With access to a running wheel (RW) in short photoperiod,
      Siberian hamsters that have undergone photoperiod-mediated weight loss over-ride
      photoperiod-drive for reduced body weight and regain weight similar to a hamster
      held in long days. These changes occur despite retaining the majority of
      hypothalamic gene expression profiles appropriate for short-day hamsters.
      Utilising the somatostatin agonist pasireotide, we recently provided evidence for
      an involvement of the growth hormone (GH) axis in the seasonal regulation of
      bodyweight. In the present study, we employed pasireotide to test for the
      possible involvement of the GH axis in RW-induced body weight regulation.
      Pasireotide successfully inhibited exercise-stimulated growth in short-day
      hamsters and this was accompanied by altered hypothalamic gene expression of key
      GH axis components. Our data provide support for an involvement of the GH axis in
      the RW response in Siberian hamsters.

PMID- 27874966
TI  - From Additivity to Cooperativity in Chemistry: Can Cooperativity Be Measured?
AB  - Cooperative effects can be observed in various research areas in chemistry;
      cooperative catalysis is well-established, the assembly of compounds on surfaces
      can be steered by cooperative effects, and supramolecular polymerization can
      proceed in a cooperative manner. In biological systems, cooperativity is observed
      in protein-protein, protein-lipid and protein-molecule interactions. Synergistic
      effects are relevant in frustrated Lewis pairs, organic multispin systems,
      multimetallic clusters and also in nanoparticles. However, a general approach to
      determine cooperativity in the different chemical systems is currently not known.
      In the present concept paper it is suggested that, at least for simpler systems
      that can be described at the molecular level, cooperativity can be defined based
      on energy considerations. For systems in which no chemical transformation occurs,
      determination of interaction energies of the whole system with respect to the
      interaction energies between all individual component pairs (subsystems) will
      allow determination of cooperativity. For systems comprising of chemical
      transformations, cooperativity can be evaluated by determining the activation
      energy of the synergistic system and by comparing this with activation energies
      of the corresponding subsystems that lack an activating moiety. For more complex
      systems, cooperativity is generally determined at a qualitative level.

PMID- 27874967
TI  - Editorial.

PMID- 27874968
TI  - Professionalization of surgical abdominal organ recovery leading to an increase
      in pancreatic allografts accepted for transplantation in the Netherlands: a
      serial analysis.
AB  - Professional abdominal organ recovery with certification has been mandatory in
      the Netherlands since 2010. This study analyses the effects of certification
      (January 2010-September 2015) on pancreas transplantation and compares it to an
      era before certification (February 2002-May 2008) for surgical injuries and the
      number of pancreases transplanted. A total of 264 cases were analysed. Eighty
      four recovered pancreases (31.8%) with surgically injuries were encountered.
      Forty-six of those were surgically salvaged for transplantation, resulting in a
      total of 226 (85.6%) being transplanted. It was found that certified surgeons
      recovered grafts from older donors (36.8 vs. 33.3; P = 0.021), more often from
      donation after circulatory death (DCD) donors (18% vs. 0%; P < 0.001) and had
      less surgical injuries (21.6% vs. 41.0%; P < 0.001). Certification (OR: 0.285; P
      < 0.001) and surgeons from a pancreas transplant centre (OR: 0.420; P = 0.002)
      were independent risk factors for surgical organ injury. Predictors for
      proceeding to the actual pancreas transplantation were a recovering surgeon from
      a pancreas transplantation centre (OR: 3.230; P = 0.003), certification (OR:
      3.750; P = 0.004), donation after brain death (DBD) (OR: 8.313; P = 0.002) and
      donor body mass index (BMI) (OR: 0.851; P = 0.023). It is concluded that
      certification in abdominal organ recovery will limit the number of surgical
      injuries in pancreas grafts which will translate in more pancreases available for
      transplantation.

PMID- 27874969
TI  - Idiopathic myelofibrosis accompanied by peritoneal extramedullary hematopoiesis
      presenting as refractory ascites in a dog.
AB  - A 2.5-year-old spayed female American Pit Bull Terrier dog presented with a
      primary complaint of chronic refractory ascites. The dog's CBC displayed a
      moderate to severe macrocytic, hypochromic, nonregenerative anemia, and a
      moderate leukopenia as result of a moderate neutropenia and monocytopenia.
      Microscopic examination of the blood smear showed marked anisocytosis, mild
      polychromasia, mild acanthocytosis and ovalocytosis, moderate schistocytosis and
      poikilocytosis, and 4 metarubricytes/100 WBC. Abdominal ultrasonography revealed
      a homogenous, mild to moderately hyperechoic appearing liver as well as marked
      amounts of speckled anechoic to slightly hypoechoic peritoneal fluid. Cytology of
      the ascitic fluid demonstrated a sterile transudate, with evidence of a chronic
      inflammatory reaction as well as erythroid and myeloid precursor cells, and a few
      megakaryocytes with occasional micromegakaryocytes. Histologic sections of bone
      marrow, spleen, and liver were examined, using routine H&E stains, as well as a
      variety of immunohistochemistry and other special stains. Histopathology of the
      bone marrow and spleen revealed varying degrees of fibrosis, erythroid, and
      myeloid hyperplasia, as well as multiple small hyperplastic clusters of
      megakaryocytes. The megakaryocytes displayed many features of atypia such as
      increased cytoplasmic basophilia and occasional abnormal chromatin clumping with
      mitoses. Histopathologic examination of the liver disclosed evidence of mild
      extramedullary hematopoiesis. This case represents the first report of canine
      idiopathic myelofibrosis associated with peritoneal extramedullary hematopoiesis,
      resulting in refractory ascites. Although idiopathic myelofibrosis is a
      relatively rare condition in dogs, this case demonstrates that ascites caused by
      peritoneal implants of hematopoietic tissue may be the initial manifestation of
      myelofibrosis.

PMID- 27874970
TI  - Tandem Aryne-Capture/Sigmatropic Rearrangement as a Metal-Free Entry to
      Functionalized N-Aryl Pyrrolidines.
AB  - We report a new method for the synthesis of novel N-aryl proline analogues. By
      reacting an aryne precursor with N-(2-malonyl) tetrahydropyridines in the
      presence of tetrabutylammonium fluoride (TBAF), a tandem aryne-capture/anion
      isomerisation/[2,3]-sigmatropic rearrangement is induced, leading to good yields
      of 3-substituted N-aryl-2-acylpyrrolidines. These products are known subunits of
      biological probes, sensors and drug-like fragments, and are not easily accessed
      directly by other methods. The reaction is also notable as the first [2,3]
      rearrangement of cyclic ammonium ylides at room temperature.

PMID- 27874971
TI  - Cefiderocol, a Siderophore Cephalosporin for Gram-Negative Bacterial Infections:
      Pharmacokinetics and Safety in Subjects With Renal Impairment.
AB  - Cefiderocol, a new injectable siderophore cephalosporin antibiotic, has promising
      in vitro and in vivo activity against Gram-negative bacteria including multidrug
      resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella
      pneumoniae. Cefiderocol is mainly renally eliminated. The pharmacokinetics and
      safety of cefiderocol in subjects with renal impairment were assessed following a
      single 1000-mg intravenous 1-hour infusion of cefiderocol. Subjects with mild,
      moderate, or severe renal impairment and end-stage renal disease (ESRD) requiring
      hemodialysis were compared with demographically (age, body mass index, and sex)
      matched healthy subjects with normal renal function. The effect of hemodialysis
      on the clearance of cefiderocol was also assessed. Total drug clearance from
      plasma (CL) and terminal half-life (t1/2 ) correlated with renal function. Ratios
      (90% confidence intervals) of area under the plasma concentration-time curve from
      0 to infinity (AUC) in mild, moderate, severe, and ESRD groups compared to those
      with normal renal function were 1.0 (0.8-1.3), 1.5 (1.2-1.9), 2.5 (2.0-3.3), and
      4.1 (3.3-5.2), respectively. Maximum plasma concentration (Cmax ) was similar
      between renal-impairment groups and the normal-renal-function group.
      Approximately 60% of cefiderocol was removed by hemodialysis for 3 to 4 hours.
      The plasma-protein-unbound fraction was similar between various renal function
      groups. The incidence of adverse events did not appear to have any correlation
      with the degree of renal impairment. Single 1000-mg intravenous doses of
      cefiderocol were generally well tolerated in subjects with impaired renal
      function except for 1 subject who discontinued due to urticaria. In conclusion,
      renal impairment impacted AUC, CL, and t1/2 without affecting Cmax . Cefiderocol
      was significantly removed by intermittent hemodialysis.

PMID- 27874972
TI  - A Hemilabile and Cooperative N-Donor-Functionalized 1,2,3-Triazol-5-Ylidene
      Ligand for Alkyne Hydrothiolation Reactions.
AB  - A series of novel cationic and neutral Rh complexes with an N-donor
      functionalized 1,2,3-triazol-5-ylidene (TRZ) ligand (in which the pendant N donor
      is NHBoc, NH2 , or NMe2 ) is described. The catalytic activity of these complexes
      was evaluated in the hydrothiolation of alkynes. Among the catalysts, a neutral
      dicarbonyl complex featuring the tethered-NBoc amido-TRZ ligand proved very
      selective for alkyne hydrothiolation with an aryl thiol. Remarkably, the reaction
      could be carried out in the absence of pyridine or base additive. In addition,
      during the reaction, no evidence for oxidative addition of the thiol S-H bond was
      observed, strongly suggesting a reaction pathway in which a bifunctional ligand
      is involved. Experimental and theoretical mechanistic investigations suggest a
      ligand-assisted deprotonation of thiol, hemilabile dissociation of amine from the
      metal, and thiolate coordination, which is indicative of a different reaction
      mechanism to those previously reported for related alkyne hydrothiolation
      reactions.

PMID- 27874973
TI  - Degradation of benzo[a]pyrene by Pleurotus ostreatus PO-3 in the presence of
      defined fungal and bacterial co-cultures.
AB  - Benzo[a]pyrene, a high molecular weight polycyclic aromatic hydrocarbon possesses
      carcinogenic, teratogenic, and mutagenic properties. The present study focuses on
      benzo[a]pyrene degradation by Pleurotus ostreatus PO-3, characterization and
      identification of metabolites produced and the extent of degradation in the
      presence of axenic culture of P. ostreatus PO-3 and defined co-cultures of the
      basidiomycete with bacteria and non-basidiomycete fungi. Thin-layer
      chromatography revealed that P. ostreatus PO-3 transformed benzo[a]pyrene to
      polar metabolites. Following degradation, appearance of numerous peaks in the
      mass spectrum indicated that benzo[a]pyrene degradation was a result of the
      metabolic activity of P. ostreatus PO-3. A degradation product corresponding to
      the m/z 284.2 was detected which could possibly be BaP-quinone, resulting from
      the oxidation of benzo[a]pyrene. Compared to the axenic culture of P. ostreatus
      PO-3 (64.3%), co-cultures of P. ostreatus PO-3 and Penicillium chrysogenum MTCC
      787 and P. ostreatus PO-3 and Pseudomonas aeruginosa MTCC 1688 could degrade 86.1
      and 75.1% of benzo[a]pyrene, respectively. Thus it could be inferred from the
      present investigation that the combined catabolic activities of P. ostreatus PO-3
      with bacteria and non-basidiomycete fungi can produce synergistic effects to
      enhance BaP degradation. The increase in the generation of polar metabolites as
      degradation products from the recalcitrant parent compound advocates the
      potential application of P. ostreatus PO-3 in benzo[a]pyrene bioremediation.

PMID- 27874974
TI  - Nanoscale Fluorescent Metal-Organic Framework@Microporous Organic Polymer
      Composites for Enhanced Intracellular Uptake and Bioimaging.
AB  - Polymer-modified metal-organic frameworks combine the advantages of both soft
      polymers and crystalline metal-organic frameworks (MOFs). It is a big challenge
      to develop simple methods for surface modification of MOFs. In this work,
      MOF@microporous organic polymer (MOP) hybrid nanoparticles (UNP) have been
      synthesized by epitaxial growth of luminescent boron-dipyrromethene (BODIPYs)
      imine MOPs on the surface of UiO-MOF seeds, which exhibit low cytotoxicity,
      smaller size distribution, well-retained pore integrity, and available functional
      sites. After folic acid grafting, the enhanced intracellular uptake and
      bioimaging was validated.

PMID- 27874975
TI  - Structural and functional brain alterations in a murine model of Angiotensin II
      induced hypertension.
AB  - Hypertension is a main risk factor for the development of cerebral small vessel
      disease (cSVD) - a major contributor to stroke and the most common cause of
      vascular dementia. Despite the increasing socioeconomic importance arising from
      cSVD, currently only a few specific treatment strategies with proven efficacy are
      known. Fundamental to the lack of specific treatments is poor understanding of
      the disease pathogenesis and a lack of appropriate animal models resembling all
      symptoms of the human disease. However, chronic hypertensive rat models have been
      shown to bear similarities to most key features of cSVD. Despite a significantly
      larger toolbox available for genotypic and phenotypic modifications compared to
      rats, mouse models of hypertension are unusual when modeling cSVD and associated
      cognitive impairment experimentally. In the present study, we therefore
      characterized hypertension-mediated cerebrovascular alterations and accompanying
      structural and functional consequences by simultaneously treating adult wild-type
      mice (C57BL/6N) with Angiotensin II (AngII) and the nitric oxide synthases
      inhibitor L-NAME for 4 weeks. Hypertension associated to cerebral alterations
      reminiscent of early-onset cSVD and vascular cognitive impairment when combined
      with additional AngII bolus injections. Most importantly, preventing the
      elevation of blood pressure (BP) protected from the development of cSVD symptoms
      and associated cognitive decline. Our data strongly support the suitability of
      this particular mouse model of AngII-induced hypertension as an appropriate
      animal model for early-onset cSVD and hence, vascular cognitive impairment,
      pathologies commonly preceding vascular dementia.

PMID- 27874976
TI  - Etidronate rescues cognitive deficits through improving synaptic transmission and
      suppressing apoptosis in 2-vessel occlusion model rats.
AB  - Vascular dementia is a neurodegenerative disorder caused by the reduction of
      cerebral blood flow. It shows a progressive cognitive impairment. In our previous
      study, we found that etidronate (ET) showed neuroprotective effects against
      glutamate-injured PC12 cells. Thus, in this study, we aimed to observe the
      effects of ET on learning and memory impairment and the related mechanism in 2
      vessel occlusion (2VO) model rats. Rats were administered a permanent bilateral
      common carotid artery occlusion to induce vascular dementia model. Two weeks
      later, 2VO model rats were treated with ET (20 mg/kg/day i.p.) for 1 week.
      Results showed that ET improved the spatial learning and memory function in 2VO
      rats detected by Morris water maze experiment. A reduced long-term potentiation
      was also rescued by ET treatment in 2VO rats. Moreover, the long-term
      potentiation-related proteins, calcium/calmodulin-dependent protein kinase II
      (CaMKII), NMDAR 2B and PSD95 were up-regulated after treatment with ET. By
      testing the levels of malondialdehyde and superoxide dismutase in 2VO rats, we
      discovered that ET lowered oxidative stress. Furthermore, ET displayed a better
      anti-apoptosis ability through detecting the levels of Bcl-2 and Bax protein and
      terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. In
      conclusion, ET shows neuroprotective effects on 2VO rats through rescuing spatial
      working memory deficits, and a possible mechanism may be related to the increased
      synaptic transmission and the inhibition of oxidative stress and apoptosis.

PMID- 27874977
TI  - Relationship Between Age and Trajectories of Rehospitalization Risk in Older
      Adults.
AB  - OBJECTIVES: To characterize the magnitude and duration of risk of
      rehospitalization according to age after hospitalization for heart failure (HF),
      acute myocardial infarction (AMI), or pneumonia. DESIGN: Retrospective cohort
      study. SETTING: U.S. hospitals (n = 4,767). PARTICIPANTS: All Medicare fee-for
      service beneficiaries aged 65 and older surviving hospitalization for HF, AMI, or
      pneumonia between October 2012 and December 2013. MEASUREMENTS: Daily risk of
      first rehospitalization for 1 year after hospital discharge was calculated
      according to age category (65-74, 75-84, >=85) after adjustment for sex, race,
      comorbidities, and median ZIP code income. Time required for adjusted
      rehospitalization risk to decline 50% from maximum value after discharge, time
      required for adjusted risk to approach a plateau period of minimal day-to-day
      change, and degree to which adjusted risk was higher in recently hospitalized
      individuals than in the general elderly population were identified. RESULTS:
      There were 414,720 hospitalizations for HF, 177,752 for AMI, and 568,304 for
      pneumonia. The adjusted risk of rehospitalization declined with increasing age
      after HF hospitalization (P < .001), rose with increasing age after AMI
      hospitalization (P < .001), and was slightly lower with increasing age after
      pneumonia hospitalization (P = .002). Adjusted risks of rehospitalization were
      high beyond 30 days after hospitalization for all ages. CONCLUSION: Although
      older age has heterogeneous relationships with rehospitalization risk, risk of
      readmission remains high for an extended time after discharge regardless of age
      or admitting condition. Condition-specific data on risk can be used to guide
      discussions on advanced care planning and strategies for longitudinal follow-up
      after hospitalization.

PMID- 27874979
TI  - Risk factors for recurrence of hypertensive disorders of pregnancy, a population
      based cohort study.
AB  - INTRODUCTION: Hypertensive disorders of pregnancy (HDP) tend to recur from one
      pregnancy to the next. The aims of the study were to assess the recurrence risk
      according to type of HDP defined by gestational age at birth and to examine
      whether recurrence is associated with the following additional risk factors for
      HDP: maternal age, smoking, inter-delivery interval, diabetes, body mass index,
      and fetal growth restriction, and to assess temporal trends in these
      associations. MATERIAL AND METHODS: All women with two singleton births in the
      Medical Birth Registry of Norway 1967-2012 (n = 742 980) were included in this
      population-based cohort study. Logistic regression was used to calculate odds
      ratios for the risk of recurrent HDP according to type of HDP. RESULTS: The
      highest odds ratio of recurrence was observed for the same type of HDP based on
      gestational age at delivery. After gestational hypertension and term
      preeclampsia, the risk for the same type to recur increased 10-fold, whereas
      after late and early preterm preeclampsia, the risk increased 27- and 97-fold,
      respectively. The recurrence of early preterm preeclampsia was less influenced by
      additional risk factors compared with term HDP. Recurrence of early preterm HDP
      was significantly lower from 1993 onwards. CONCLUSIONS: Recurrent HDP tended to
      be of the same type as the previous HDP. Risk of recurrence associated with
      additional risk factors was observed particularly after term. The odds ratio of
      recurrence of early preterm HDP was significantly lower from 1993 onwards.

PMID- 27874980
TI  - Nurses' shift reports: a systematic literature search and critical review of
      qualitative field studies.
AB  - AIMS AND OBJECTIVES: To identify reporting practices that feature in studies of
      nurses' shift reports across diverse nursing specialities. The objectives were to
      perform an exhaustive systematic literature search and to critically review the
      quality and findings of qualitative field studies of nurses' shift reports.
      BACKGROUND: Nurses' shift reports are routine occurrences in healthcare
      organisations that are viewed as crucial for patient outcomes, patient safety and
      continuity of care. Studies of communication between nurses attend primarily to
      1:1 communication and analyse the adequacy and accuracy of patient information
      and feature handovers at the bedside. Still, verbal reports between groups of
      nurses about patients are commonplace. Shift reports are obvious sites for
      studying the situated accomplishment of professional nursing at the group level.
      This review is focused exclusively on qualitative field research for nuanced and
      contextualised insights into nurses' everyday shift reporting practices. DESIGN:
      The study is a systematic literature search and critical review of qualitative
      field analyses of nurses' shift reports. We searched in the databases CIHAHL,
      PubMed and PsycINFO and identified and reviewed 19 articles published 1992-2014.
      Data were systematically extracted using criteria for the evaluation of
      qualitative research reports. RESULTS: The studies described shift report
      practices and identified several factors contributing to distribution of clinical
      knowledge. Shift report practices were described as highly conventionalised and
      locally situated, but with occasional opportunities for improvisation and
      negotiation between nurses. Finally, shift reports were described as
      multifunctional meetings, with individual and social effects for nurses and
      teams. CONCLUSION: Innovations in between-shift communications can benefit from
      this analysis, by providing for the many functions of handovers that are revealed
      in field studies. RELEVANCE TO CLINICAL PRACTICE: Leaders and practising nurses
      may consider what are the best opportunities for nurses to work up clinical
      knowledge and negotiate care.

PMID- 27874978
TI  - The treatment of bacterial vaginosis in pregnancy with clindamycin to reduce the
      risk of infection-related preterm birth: a response to the Danish Society of
      Obstetrics and Gynecology guideline group's clinical recommendations.
AB  - Preterm birth is the major cause of perinatal mortality and morbidity worldwide.
      Infection/inflammation is responsible for a significant percentage of preterm
      birth, particularly at early gestations. A recent clinical recommendation by a
      guidelines group of the Danish Society of Obstetrics and Gynecology advised
      against the use of clindamycin for the treatment of bacterial vaginosis in
      pregnancy to reduce the risk of spontaneous preterm birth based on lack of
      evidence of efficacy. We believe that the evidence for the use of clindamycin for
      this indication is robust and that this recommendation was reached erroneously on
      the basis of flawed inclusion criteria: the inclusion of an unpublished study
      with poorly diagnosed bacterial vaginosis and the exclusion of an important
      pivotal study on the use of clindamycin in early pregnancy for the prevention of
      preterm birth. Had these errors been corrected, the conclusions would have been
      different.

PMID- 27874982
TI  - Rethinking presence: a grounded theory of nurses and teleconsultation.
AB  - AIMS AND OBJECTIVES: To develop a theory that offered an evidence-based insight
      into the use of teleconsultation by nurses. BACKGROUND: Teleconsultation is the
      use of video to facilitate real-time, remote interaction between healthcare
      practitioners and patients. Although its popularity is growing, there is little
      understanding of how teleconsultation impacts on the role of nurses. DESIGN: The
      study adopted a constructivist grounded theory method, supplemented by the use of
      Straussian analytical approaches. METHODS: Using selective and theoretical
      approaches, registered nurses with experience of using video in health care were
      sampled. Data were collected using semi-structured interviews exploring
      experiences, knowledge and feelings surrounding teleconsultation. Interviews were
      recorded, transcribed and subjected to three-stage, nonlinear manual analysis
      (open, axial and selective coding). RESULTS: Theoretical saturation occurred
      after 17 interviews. The core category identified from the data was 'nursing
      presence' Four subcategories of nursing presence were identified: operational,
      clinical, therapeutic and social. The degree to which presence could be achieved
      was dependent upon three influencing factors - enablers, constraints and
      compensation. CONCLUSIONS: Nurses provide different types of presence during
      teleconsultation, with the degree of presence dependent on specific
      characteristics of video-mediated communication. Where the use of video
      constrains the delivery of presence, nurses use a range of compensatory
      mechanisms to enhance patient care. RELEVANCE TO CLINICAL PRACTICE:
      Teleconsultation provides an innovative approach to enhancing the delivery of
      health care. This study provides nurses with insight into the impact of
      teleconsultation on their professional role, and an understanding of how best to
      use video-mediated communication to support patient care.

PMID- 27874983
TI  - Physical health monitoring in mental health settings: a study exploring mental
      health nurses' views of their role.
AB  - AIMS AND OBJECTIVES: To explore nurses' views of their role in the screening and
      monitoring of the physical care needs of people with serious mental illness in a
      mental health service provider. BACKGROUND: There is increasing awareness through
      research that people with serious mental illness disproportionately experience
      and die early from physical health conditions. Mental health nurses are best
      placed as front-line workers to offer screening, monitoring and interventions;
      however, their views on physical care interventions are not studied often.
      DESIGN: Qualitative exploratory study. METHODS: The study was carried out in a
      mental health inpatient centre in England. Volunteer sampling was adopted for the
      study with a total target sample of (n = 20) nurses from three inpatient wards.
      Semistructured interviews were conducted with (n = 10) registered mental health
      nurses who had consented to take part in the study. Inductive data analysis and
      theme development were guided by a thematic analytic framework. RESULTS:
      Participants shared a clear commitment regarding their role regarding physical
      health screening and monitoring in mental health settings. Four themes emerged as
      follows: features of current practice and physical health monitoring; perceived
      barriers to physical health monitoring; education and training needs; and
      strategies to improve physical health monitoring. CONCLUSIONS: Nurses were
      unequivocal in their resolve to ensure good standard physical health monitoring
      and screening interventions in practice. However, identified obstacles have to be
      addressed to ensure that physical health screening and monitoring is integrated
      adequately in everyday clinical activities. Achieving this would require
      improvements in nurses' training, and an integrated multiservice and team-working
      approach. RELEVANCE TO CLINICAL PRACTICE: Attending to the physical health needs
      of people with serious mental illness has been associated with multiple
      improvements in both mental and physical health; nurses have a vital role to play
      in identifying and addressing causes of poor physical health to improve physical
      health outcomes in people with serious mental illness.

PMID- 27874984
TI  - Maternity groups in the postpartum period at well child clinics - mothers'
      experiences.
AB  - AIMS AND OBJECTIVES: To explore mothers' experiences as participants in maternity
      groups at well child clinics (WCCs). BACKGROUND: The level of psychological
      distress that new mothers have may be related to the quantity of social support
      they receive. Maternity groups to support new parents have a long tradition at
      WCCs in Norway, and most of the clinics have offered these groups. However, there
      is little knowledge about mothers' experiences of participating in these groups.
      DESIGN: Qualitative design. METHOD: Focus group interviews with mothers who had
      participated in maternity groups facilitated by public health nurses (PHNs) at
      WCCs. Interpretive description was used to analyse the transcripts from the
      interviews. RESULTS: Eight focus group interviews were conducted with a total of
      30 mothers who had participated in maternity groups at WCCs in two counties in
      eastern Norway. The analysis resulted in one main category, 'The maternity
      group's salutogenic importance' and three subcategories, 'Networks that can last
      for many years', 'Fellowship with others in the same situation' and 'Become
      confident in mothering'. CONCLUSION: Mothers wanted fellowship and found it
      important to share experiences with other mothers. Maternity groups offered to
      parents are essential to meet parents' need to discuss experiences and challenges
      related to parenting. Maternity groups can also create a basis for establishing a
      social network for those who want it. RELEVANCE TO CLINICAL PRACTICE: Well child
      clinics should offer all mothers the opportunity to participate in groups to
      strengthen their social relations and their confidence in parenting. PHNs play an
      important role in facilitating groups for first-time parents. Group leadership
      can influence how mothers in a group connect and whether the parental role is
      affected.

PMID- 27874985
TI  - Life's a beach - the colonization of the terrestrial environment.

PMID- 27874986
TI  - Bridging evolution and development in plants.

PMID- 27874987
TI  - Retraction.
AB  - This article corrects: Retracted: Three BUB1 and BUBR1/MAD3-related spindle
      assembly checkpoint proteins are required for accurate mitosis in Arabidopsis.
      New Phytologist 205: 202-215. Article first published online: 29 September 2014.
      This article has been retracted at the request of: Editor-in-Chief and Author
      'Three BUB1 and BUBR1/MAD3-related spindle assembly checkpoint proteins are
      required for accurate mitosis in Arabidopsis', by Paganelli L, Caillaud M-C,
      Quentin M, Damiani I, Govetto B, Lecomte P, Karpov, PA, Abad P, Chaboute M-E and
      Favery B. The above article, first published online on Wiley Online Library
      (wileyonlinelibrary.com), and in New Phytologist 205: 202-215, has been retracted
      by agreement between the authors, the journal Editor-in-Chief, Alistair
      Hetherington, and John Wiley & Sons Ltd. Since publication of the above article,
      it has been brought to our attention that errors occurred in the construction of
      Figs 1 and 2(a); some components were inappropriately edited and duplicated,
      including the duplication and editing of images that first appeared in Caillaud
      et al. (2009), which were used by the authors as a basic template. Consequently,
      the integrity of the yeast two-hybrid experiments reported in the article is
      undermined, and, with agreement of all parties, the decision has been made to
      retract this article. We apologize for any inconvenience the publication of this
      work may have caused our readers. References Caillaud MC, Paganelli L, Lecomte P,
      Deslandes L, Quentin M, Pecrix Y, Le Bris M, Marfaing N, Abad P, Favery B. 2009.
      Spindle assembly checkpoint protein dynamics reveal conserved and unsuspected
      roles in plant cell division. PLoS One 4: e6757. Paganelli L, Caillaud M-C,
      Quentin M, Damiani I, Govetto B, Lecomte P, Karpov PA, Abad P, Chaboute M-E,
      Favery B. 2015. Three BUB1 and BUBR1/MAD3-related spindle assembly checkpoint
      proteins are required for accurate mitosis in Arabidopsis. New Phytologist 205:
      202-215.

PMID- 27874988
TI  - Clash between the borders: spotlight on apoplastic processes in plant-microbe
      interactions.

PMID- 27874989
TI  - Too many partners in root-shoot signals. Does hydraulics qualify as the only
      signal that feeds back over time for reliable stomatal control?

PMID- 27874991
TI  - Katie J. Field.

PMID- 27874990
TI  - Plant volatile-mediated signalling and its application in agriculture: successes
      and challenges.
AB  - 856 I. 856 II. 857 III. 858 IV. 859 V. 860 VI. 862 VII. 863 VIII. 864 IX. 866 866
      References 866 SUMMARY: The mediation of volatile secondary metabolites in
      signalling between plants and other organisms has long been seen as presenting
      opportunities for sustainable crop protection. Initially, exploitation of
      interactions between plants and other organisms, particularly insect pests,
      foundered because of difficulties in delivering, sustainably, the signal systems
      for crop protection. We now have mounting and, in some cases, clear practical
      evidence for successful delivery by companion cropping or next-generation genetic
      modification (GM). At the same time, the type of plant signalling being exploited
      has expanded to signalling from plants to organisms antagonistic to pests, and to
      plant stress-induced, or primed, plant-to-plant signalling for defence and growth
      stimulation.

PMID- 27874992
TI  - Editorial: On the road to health equity: incorporating culture into research.

PMID- 27874993
TI  - Bismuth Perfluoroalkylphosphinates: New Catalysts for Application in Organic
      Syntheses.
AB  - Commercially available BiPh3 was treated with perfluoroalkylphosphinic acids [for
      example, (C2 F5 )2 P(O)OH] to generate novel, highly Lewis acidic bismuth(III)
      perfluoroalkylphosphinates of the type Phx Bi[RF2 PO2 ]3-x (x=0, 1, 2) (RF =-C2
      F5 , -C4 F9 ). The first bismuth(V) perfluoroalkylphosphinate, Ph3 Bi[(C2 F5 )2
      PO2 ]2 , was synthesized from Ph3 BiCl2 and Ag[(C2 F5 )2 PO2 ]. Examples for the
      successful application of the catalytically active bismuth(III) and bismuth(V)
      phosphinates in carbon-carbon bond forming reactions, such as Friedel-Crafts
      acylation and alkylation, Diels-Alder, Strecker and Mannich reaction, are
      presented.

PMID- 27874994
TI  - SSRI and SNRI use during pregnancy and the risk of persistent pulmonary
      hypertension of the newborn.
AB  - AIM: The use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy
      may be associated with an increased risk of persistent pulmonary hypertension of
      the newborn (PPHN). Limited data are available on the risk of PPHN associated
      with serotonin norepinephrine reuptake inhibitors (SNRIs). We aimed to quantify
      both associations. METHODS: Using data from the Quebec Pregnancy Cohort between
      1998 and 2009, we included women covered by the provincial drug plan who had a
      singleton live birth. Exposure categories were SSRI, SNRI and other
      antidepressant use; non-users were considered as the reference category.
      Generalized estimating equation models were used to obtain risk estimates and 95%
      confidence intervals (CIs). Confounding by indication was minimized by adjusting
      for history of maternal depression/anxiety before pregnancy. RESULTS: Overall,
      143 281 pregnancies were included; PPHN was identified in 0.2% of newborns.
      Adjusting for maternal depression, and other potential confounders, SSRI use
      during the second half of pregnancy was associated with an increased risk of PPHN
      [adjusted odds ratio (aOR) 4.29, 95% CI 1.34, 13.77] compared with non-use of
      antidepressants; SNRI use during the same time window was not statistically
      associated with the risk of PPHN (aOR 0.59, 95% CI 0.06, 5.62). Use of SSRIs and
      SNRIs before the 20th week of gestation was not associated with the risk of PPHN.
      CONCLUSIONS: Use of SSRIs in the second half of pregnancy was associated with the
      risk of PPHN. Given our results on SNRIs and the lack of statistical power for
      these analyses, it is unclear whether SNRI use during pregnancy also increases
      the risk of PPHN.

PMID- 27874997
TI  - Considerations for assessing model averaging of regression coefficients.
AB  - Model choice is usually an inevitable source of uncertainty in model-based
      statistical analyses. While the focus of model choice was traditionally on
      methods for choosing a single model, methods to formally account for multiple
      models within a single analysis are now accessible to many researchers. The
      specific technique of model averaging was developed to improve predictive ability
      by combining predictions from a set of models. However, it is now often used to
      average regression coefficients across multiple models with the ultimate goal of
      capturing a variable's overall effect. This use of model averaging implicitly
      assumes the same parameter exists across models so that averaging is sensible.
      While this assumption may initially seem tenable, regression coefficients
      associated with particular explanatory variables may not hold equivalent
      interpretations across all of the models in which they appear, making explanatory
      inference about covariates challenging. Accessibility to easily implementable
      software, concerns about being criticized for ignoring model uncertainty, and the
      chance to avoid having to justify choice of a final model have all led to the
      increasing popularity of model averaging in practice. We see a gap between the
      theoretical development of model averaging and its current use in practice,
      potentially leaving well-intentioned researchers with unclear inferences or
      difficulties justifying reasons for using (or not using) model averaging. We
      attempt to narrow this gap by revisiting some relevant foundations of regression
      modeling, suggesting more explicit notation and graphical tools, and discussing
      how individual model results are combined to obtain a model averaged result. Our
      goal is to help researchers make informed decisions about model averaging and to
      encourage question-focused modeling over method-focused modeling.

PMID- 27874995
TI  - Changes in self-efficacy, collective efficacy and patient outcome following
      interprofessional simulation training on postpartum haemorrhage.
AB  - AIMS AND OBJECTIVES: To examine whether interprofessional simulation training on
      management of postpartum haemorrhage enhances self-efficacy and collective
      efficacy and reduces the blood transfusion rate after birth. BACKGROUND:
      Postpartum haemorrhage is a leading cause of maternal morbidity and mortality
      worldwide, although it is preventable in most cases. Interprofessional simulation
      training might help improve the competence of health professionals dealing with
      postpartum haemorrhage, and more information is needed to determine its
      potential. DESIGN: Multimethod, quasi-experimental, pre-post intervention design.
      METHODS: Interprofessional simulation training on postpartum haemorrhage was
      implemented for midwives, obstetricians and auxiliary nurses in a university
      hospital. Training included realistic scenarios and debriefing, and a measurement
      scale for perceived postpartum haemorrhage-specific self-efficacy, and collective
      efficacy was developed and implemented. Red blood cell transfusion was used as
      the dependent variable for improved patient outcome pre-post intervention.
      RESULTS: Self-efficacy and collective efficacy levels were significantly
      increased after training. The overall red blood cell transfusion rate did not
      change, but there was a significant reduction in the use of >=5 units of blood
      products related to severe bleeding after birth. CONCLUSION: The study
      contributes to new knowledge on how simulation training through mastery and
      vicarious experiences, verbal persuasion and psychophysiological state might
      enhance postpartum haemorrhage-specific self-efficacy and collective efficacy
      levels and thereby predict team performance. The significant reduction in severe
      postpartum haemorrhage after training, indicated by reduction in >=5 units of
      blood transfusions, corresponds well with the improvement in collective efficacy,
      and might reflect the emphasis on collective efforts to counteract severe cases
      of postpartum haemorrhage. RELEVANCE TO CLINICAL PRACTICE: Interprofessional
      simulation training in teams may contribute to enhanced prevention and management
      of postpartum haemorrhage, shown by a significant increase in perceived efficacy
      levels combined with an indicated reduction of severe postpartum haemorrhage
      after training.

PMID- 27874996
TI  - Patients' self-perceived burden, caregivers' burden and quality of life for
      amyotrophic lateral sclerosis patients: a cross-sectional study.
AB  - AIMS AND OBJECTIVES: This study surveys the quality of life of amyotrophic
      lateral sclerosis patients and the factors associated with amyotrophic lateral
      sclerosis patients' self-perceived burden and their caregivers' burden.
      BACKGROUND: Burdens of patients with amyotrophic lateral sclerosis and their
      caregivers in Chinese population are largely unknown. DESIGN: A cross-sectional
      study was conducted among 81 pairs of amyotrophic lateral sclerosis patients and
      their caregivers. METHODS: Amyotrophic lateral sclerosis patients' self-perceived
      burden and caregivers' burden were assessed by the Self-Perceived Burden Scale
      and Zarit-Burden Interview, respectively. Quality of life of amyotrophic lateral
      sclerosis patients was measured using the World Health Organization Quality of
      Life-Bref. The amyotrophic lateral sclerosis Functional Rating Scale-Revised
      questionnaire was used to estimate patients' physical function. RESULTS: Both
      patients and caregivers reported a mild to moderate burden. The World Health
      Organization quality of life-Bref scores were decreased in respondents with lower
      amyotrophic lateral sclerosis Functional Rating Scale-Revised, higher Self
      Perceived Burden Scale and higher Zarit-Burden Interview scores. Self-Perceived
      Burden Scale scores were associated with patients' knowledge of amyotrophic
      lateral sclerosis, respiratory function and female sex. Zarit-Burden Interview
      scores were associated with caregivers' age, patients' motor function and out-of
      pocket payment. CONCLUSION: With increase in amyotrophic lateral sclerosis
      patients' self-perceived burden and caregivers' burden, quality of life of
      amyotrophic lateral sclerosis patients decreased. Female patients, who had known
      more about the disease, and those with severe respiratory dysfunction were
      subject to higher self-perceived burden. Older caregivers and caregivers of
      patients with severe motor dysfunction and more out-of-pocket payment experienced
      more care burdens. RELEVANCE TO CLINICAL PRACTICE: Our study suggests that paying
      more attention to female amyotrophic lateral sclerosis patients might benefit
      patients in China or other South-East Asian countries under the Confucian concept
      of ethics. There is an urgent demand to expand medical insurance coverage to
      cover amyotrophic lateral sclerosis in China and other developing countries. Long
      and adequate supports are needed for relieving caregiver's burden. To improve the
      quality of life of patients, relieving the patients' SBP and caregivers' burden
      is likely to be not only required, but also essential.

PMID- 27874998
TI  - Factors predictive of the efficacy of bezafibrate therapy in patients with
      primary sclerosing cholangitis.
AB  - AIM: Primary sclerosing cholangitis (PSC) is a rare cholestatic disease. We
      previously reported the effects of bezafibrate on elevated hepatobiliary enzyme
      levels in patients with this disease both retrospectively and prospectively. In
      this study, we assessed factors predictive of bezafibrate efficacy. METHODS:
      Twenty-five patients with PSC, who underwent bezafibrate therapy (400 mg per day)
      from November 2006 to June 2015, were evaluated. Treatment was judged as being
      effective if the levels of all of the hepatobiliary enzymes decreased after 12
      weeks. We investigated the patients' characteristics, disease history,
      concomitant medications, liver function, and liver stiffness. RESULTS: The
      efficacy rate of bezafibrate was 60% (15/25 patients). The efficacy rate in
      patients graded as Child-Pugh class A was significantly higher (75% [15/20]) than
      that in patients graded as class B (0% [0/5], P < 0.01). Non-responders had
      higher liver stiffness values (18.0 vs. 8.8 kPa, P = 0.19), and concomitantly
      used ursodeoxycholic acid more frequently (100% vs. 73%, P = 0.12) than
      responders. CONCLUSIONS: We could not elucidate the factors predictive for
      bezafibrate efficacy for the treatment of PSC. However, bezafibrate was more
      effective for patients with preserved liver function (Child-Pugh class A) when it
      was prescribed before progression of liver fibrosis and failure of
      ursodeoxycholic acid therapy.

PMID- 27874999
TI  - Environmental controls on canopy foliar nitrogen distributions in a Neotropical
      lowland forest.
AB  - Distributions of foliar nutrients across forest canopies can give insight into
      their plant functional diversity and improve our understanding of biogeochemical
      cycling. We used airborne remote sensing and partial least squares regression to
      quantify canopy foliar nitrogen (foliar N) across ~164 km2 of wet lowland
      tropical forest in the Osa Peninsula, Costa Rica. We determined the relative
      influence of climate and topography on the observed patterns of foliar N using a
      gradient boosting model technique. At a local scale, where climate and substrate
      were constant, we explored the influence of slope position on foliar N by
      quantifying foliar N on remnant terraces, their adjacent slopes, and knife-edged
      ridges. In addition, we climbed and sampled 540 trees and analyzed foliar N in
      order to quantify the role of species identity (phylogeny) and environmental
      factors in predicting foliar N. Observed foliar N heterogeneity reflected
      environmental factors working at multiple spatial scales. Across the larger
      landscape, elevation and precipitation had the highest relative influence on
      predicting foliar N (30% and 24%), followed by soils (15%), site exposure (9%),
      compound topographic index (8%), substrate (6%), and landscape dissection (6%).
      Phylogeny explained ~75% of the variation in the field collected foliar N data,
      suggesting that phylogeny largely underpins the response to the environmental
      factors. Taken together, these data suggest that a large fraction of the variance
      in foliar N across the landscape is proximately driven by species composition,
      though ultimately this is likely a response to abiotic factors such as climate
      and topography. Future work should focus on the mechanisms and feedbacks
      involved, and how shifts in climate may translate to changes in forest function.

PMID- 27875000
TI  - Combined hepatocellular-cholangiocarcinoma: Gadoxetic acid-enhanced MRI findings
      correlated with pathologic features and prognosis.
AB  - PURPOSE: To evaluate gadoxetic acid-enhanced magnetic resonance imaging (MRI)
      findings of combined hepatocellular cholangiocarcinoma (cHCC-CC) with special
      emphasis on correlation of MRI findings with histopathologic tumor
      characteristics and survival outcomes after curative surgery. MATERIALS AND
      METHODS: Our Institutional Review Board approved this study, with a waiver of
      informed consent. For 82 patients (64 men, 18 women; mean age, 54.0 years; age
      range, 30-81) with surgically confirmed cHCC-CCs, we evaluated clinical features,
      histologic findings, and tumor morphologic and enhancement features on gadoxetic
      acid-enhanced liver MRI at 1.5T (n = 67) or 3.0T (n = 15). Imaging features of
      cHCC-CCs were correlated with pathologic findings according to the 2010 World
      Health Organization classification system. Tumors were categorized as
      hypervascular or nonhypervascular based on arterial phase enhancement and were
      compared with respect to overall and recurrence-free survival after curative
      intent surgery. RESULTS: Of the 82 lesions, 48 showing global arterial phase
      enhancement were categorized as the hypervascular group, while 34 lesions
      demonstrating rim, peripheral, or isoenhancement were categorized as the
      nonhypervascular group. There was no significant difference in MRI findings
      between pathologic tumor types (classical type versus stem cell feature type, P =
      0.324-1.0). Compared with the nonhypervascular group, the hypervascular group had
      a larger HCC component (P = 0.014), smaller CC component (P = 0.001), and lesser
      amount of fibrotic stroma (P = 0.006) on pathologic analysis and was an
      independent factor associated with better overall survival after surgical
      resection (P = 0.033). CONCLUSION: Gadoxetic acid-enhanced MRI findings of cHCC
      CCs were diverse, reflecting heterogeneous histologic features. The hypervascular
      group on MRI is associated with a larger HCC component, smaller CC component,
      less fibrotic stroma, and better overall survival after curative surgery than the
      nonhypervascular group. LEVEL OF EVIDENCE: 4 J. MAGN. RESON. IMAGING 2017;46:267
      280.

PMID- 27875001
TI  - Patient- and family-centred care in the intensive care unit: a challenge in the
      daily practice of healthcare professionals.
AB  - AIMS AND OBJECTIVES: To evaluate the impact of supportive interventions perceived
      by both the intensive care unit patients' relatives and the healthcare providers,
      such as deferred intake interviews for providing information and discussing the
      emotional impacts, encouragement to keep a diary, and the introduction of weekly
      psychosocial rounds, on the perceptions of relatives of patients in the intensive
      care unit. BACKGROUND: Patient- and family-centred care is gaining interest, with
      a shift from provider-centric norms to care arranged around patients' and
      relatives individual beliefs and needs. This is expected to have a positive
      influence on the quality of care. Communication is one of the most important
      factors impacting the perceived quality of care in the intensive care unit from
      the perspective of patients' relatives. New interventions have been introduced to
      help the patients' relatives to meet their communication needs. DESIGN: A time
      trend quantitative design. METHODS: Two convenience samples of relatives were
      included (in 2012 and 2013) in four different intensive care units from a large
      university medical centre in the Netherlands. RESULTS: Survey data from 211
      relatives (75% net response rate in 2012) and 123 relatives (66% net response
      rate in 2013) were used for the analysis. The second measurement showed
      significant improvements regarding informational aspects of care, clarification
      of roles in participatory caretaking and shared decision-making. CONCLUSION: The
      results suggest that the additional support offered to patients' relatives
      increased perceived quality of care, particularly with respect to informational
      needs. However, patient- and family-centred care still requires a change in the
      mindset of healthcare professionals. This new point of view should overcome
      perceived barriers and foster a culture of partnership with patients' relatives
      in the intensive care unit. RELEVANCE TO CLINICAL PRACTICE: Training in providing
      psychosocial support for the needs of relatives leads to a stronger perception of
      patient-centredness.

PMID- 27875003
TI  - Long time horizon for adaptive management to reveal predation effects in a salmon
      fishery.
AB  - Predator-prey interactions shape ecosystem structure and function, potentially
      limiting the productivity of valuable species. Simultaneously, stochastic
      environmental forcing affects species productivity, often through unknown
      mechanisms. The interacting effects of trophic and environmental conditions
      complicate management of exploited ecosystems and have motivated calls for more
      holistic management via ecosystem-based approaches, yet the limitations to these
      approaches are not widely appreciated. The Chignik salmon fishery in Alaska is
      managed to achieve maximum sustainable yield for sockeye salmon, though research
      suggests that predation by less economically valuable, and thus not targeted,
      coho salmon during juvenile rearing limits the productivity of sockeye salmon. We
      examined the relationship between historical sockeye salmon recruitment and coho
      salmon abundance observed in the Chignik system and could not detect a clear
      effect of coho salmon abundance on sockeye salmon productivity, given existing
      data. Using simulation models, we examined the probability of detecting a known
      predation effect on sockeye salmon recruitment in the presence of observation
      error in coho salmon abundance and stochasticity in sockeye salmon recruitment.
      Increased recruitment stochasticity reduced the ability to detect predator
      effects in recruitment, an effect further strengthened when low frequency
      environmental variation was added to the system. Further, increased observation
      error biased estimates of predator effects towards zero. Thus, in systems with
      high observation error on predator abundances, estimates of predation effects
      will be substantially weaker than true effects. We examined the effects of
      stochasticity on the ability of an adaptive management program to learn about
      ecosystem structure and detect an effect of management actions intended to
      release a prey species from its predators. Simulation models revealed that even
      under scenarios of large predation effects on sockeye salmon, stochastic
      recruitment masked detection of an effect of increased coho salmon harvest for
      nearly a decade. These results highlight the challenges inherent in ecosystem
      based management of predator-prey systems due to mismatched timescales of
      ecosystem dynamics and the willingness of stakeholders to risk losses in order to
      test uncertain hypotheses. It is critical for stakeholders considering EBFM
      (ecosystem-based fisheries management) and adaptive management strategies to be
      aware of the potential timelines of perceiving ecosystem change.

PMID- 27875002
TI  - Superparamagnetic nanoparticle-enhanced MRI of Alzheimer's disease plaques and
      activated microglia in 3X transgenic mouse brains: Contrast optimization.
AB  - PURPOSE: To optimize magnetic resonance imaging (MRI) of antibody-conjugated
      superparamagnetic nanoparticles for detecting amyloid-beta plaques and activated
      microglia in a 3X transgenic mouse model of Alzheimer's disease. MATERIALS AND
      METHODS: Ten 3X Tg mice were fed either chow or chow containing 100 ppm
      resveratrol. Four brains, selected from animals injected with either anti-amyloid
      targeted superparamagnetic iron oxide nanoparticles, or anti-Iba-1-conjugated
      FePt-nanoparticles, were excised, fixed with formalin, and placed in Fomblin for
      ex vivo MRI (11.7T) using multislice-multiecho, multiple gradient echo, rapid
      acquisition with relaxation enhancement, and susceptibility-weighted imaging
      (SWI). Abeta plaques and areas of neuroinflammation appeared as hypointense
      regions whose number, location, and Z-score were measured as a function of
      sequence type and echo time. RESULTS: The MR contrast was due to the shortening
      of the transverse relaxation time of the plaque-adjacent tissue water. A
      theoretical analysis of this effect showed that the echo time was the primary
      determinant of plaque contrast and was used to optimize Z-scores. The Z-scores of
      the detected lesions varied from 21 to 34 as the echo times varied from 4 to 25
      msec, with SWI providing the highest Z-score and number of detected lesions.
      Computation of the entire plaque and activated microglial distributions in 3D
      showed that resveratrol treatment led to a reduction of ~24-fold of Abeta plaque
      density and ~4-fold in microglial activation. CONCLUSION: Optimized MRI of
      antibody-conjugated superparamagnetic nanoparticles served to reveal the 3D
      distributions of both Abeta plaques and activated microglia and to measure the
      effects of drug treatments in this 3X Tg model. LEVEL OF EVIDENCE: 1 Technical
      Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:574-588.

PMID- 27875004
TI  - Grassland management impacts on soil carbon stocks: a new synthesis.
AB  - Grassland ecosystems cover a large portion of Earths' surface and contain
      substantial amounts of soil organic carbon. Previous work has established that
      these soil carbon stocks are sensitive to management and land use changes:
      grazing, species composition, and mineral nutrient availability can lead to
      losses or gains of soil carbon. Because of the large annual carbon fluxes into
      and out of grassland systems, there has been growing interest in how changes in
      management might shift the net balance of these flows, stemming losses from
      degrading grasslands or managing systems to increase soil carbon stocks (i.e.,
      carbon sequestration). A synthesis published in 2001 assembled data from hundreds
      of studies to document soil carbon responses to changes in management. Here we
      present a new synthesis that has integrated data from the hundreds of studies
      published after our previous work. These new data largely confirm our earlier
      conclusions: improved grazing management, fertilization, sowing legumes and
      improved grass species, irrigation, and conversion from cultivation all tend to
      lead to increased soil C, at rates ranging from 0.105 to more than 1 Mg C.ha-1
      .yr-1 . The new data include assessment of three new management practices: fire,
      silvopastoralism, and reclamation, although these studies are limited in number.
      The main area in which the new data are contrary to our previous synthesis is in
      conversion from native vegetation to grassland, where we find that across the
      studies the average rate of soil carbon stock change is low and not significant.
      The data in this synthesis confirm that improving grassland management practices
      and conversion from cropland to grassland improve soil carbon stocks.

PMID- 27875005
TI  - Asunaprevir/daclatasvir and sofosbuvir/ledipasvir for recurrent hepatitis C
      following living donor liver transplantation.
AB  - AIM: This study aimed to clarify the efficacy and safety of interferon-free
      therapy using asunaprevir and daclatasvir, or sofosbuvir and ledipasvir for post
      living donor liver transplantation (LDLT) recipients with hepatitis C virus
      (HCV). METHODS: A retrospective cohort study of LDLT recipients with HCV genotype
      1b treated with asunaprevir (100 mg twice daily) and daclatasvir (60 mg once
      daily), or sofosbuvir (400 mg/day) and ledipasvir (90 mg/day) was carried out.
      RESULTS: Ten patients without mutations in the area of L31 and Y93 completed the
      treatment with asunaprevir and daclatasvir. Five of them had end-stage chronic
      kidney disease, including three hemodialysis patients. Of the 10 patients, nine
      completed the protocol of 24 weeks; one stopped the treatment due to the
      development of aortic valve stenosis. All nine patients who completed the 24-week
      treatment protocol achieved end of treatment response. Nineteen patients received
      treatment with sofosbuvir and ledipasvir. Of the 19 patients, 18 completed the
      protocol of 12 weeks; one stopped treatment due to severe interstitial pneumonia.
      All 18 patients who completed the 12-week treatment protocol achieved end of
      treatment response. All patients in both treatment groups who completed the
      regimen and reached 3 months after the end of treatment achieved sustained
      virological response at 12 weeks after treatment. Liver functions were
      significantly improved at the end of treatment, and no adverse events were
      observed. CONCLUSIONS: Interferon-free therapy using asunaprevir and daclatasvir,
      or sofosbuvir and ledipasvir, is highly effective for post-LDLT recipients with
      HCV genotype 1b.

PMID- 27875007
TI  - Landscape variation in tree regeneration and snag fall drive fuel loads in 24
      year old post-fire lodgepole pine forests.
AB  - Escalating wildfire in subalpine forests with stand-replacing fire regimes is
      increasing the extent of early-seral forests throughout the western USA. Post
      fire succession generates the fuel for future fires, but little is known about
      fuel loads and their variability in young post-fire stands. We sampled fuel
      profiles in 24-year-old post-fire lodgepole pine (Pinus contorta var. latifolia)
      stands (n = 82) that regenerated from the 1988 Yellowstone Fires to answer three
      questions. (1) How do canopy and surface fuel loads vary within and among young
      lodgepole pine stands? (2) How do canopy and surface fuels vary with pre- and
      post-fire lodgepole pine stand structure and environmental conditions? (3) How
      have surface fuels changed between eight and 24 years post-fire? Fuel complexes
      varied tremendously across the landscape despite having regenerated from the same
      fires. Available canopy fuel loads and canopy bulk density averaged 8.5 Mg/ha
      (range 0.0-46.6) and 0.24 kg/m3 (range: 0.0-2.3), respectively, meeting or
      exceeding levels in mature lodgepole pine forests. Total surface-fuel loads
      averaged 123 Mg/ha (range: 43-207), and 88% was in the 1,000-h fuel class.
      Litter, 1-h, and 10-h surface fuel loads were lower than reported for mature
      lodgepole pine forests, and 1,000-h fuel loads were similar or greater. Among
      plot variation was greater in canopy fuels than surface fuels, and within-plot
      variation was greater than among-plot variation for nearly all fuels. Post-fire
      lodgepole pine density was the strongest positive predictor of canopy and fine
      surface fuel loads. Pre-fire successional stage was the best predictor of 100-h
      and 1,000-h fuel loads in the post-fire stands and strongly influenced the size
      and proportion of sound logs (greater when late successional stands had burned)
      and rotten logs (greater when early successional stands had burned). Our data
      suggest that 76% of the young post-fire lodgepole pine forests have 1,000-h fuel
      loads that exceed levels associated with high-severity surface fire potential,
      and 63% exceed levels associated with active crown fire potential. Fire rotations
      in Yellowstone National Park are predicted to shorten to a few decades and this
      prediction cannot be ruled out by a lack of fuels to carry repeated fires.

PMID- 27875006
TI  - The mental healthcare needs of undocumented migrants: an exploratory analysis of
      psychological distress and living conditions among undocumented migrants in
      Norway.
AB  - AIMS AND OBJECTIVES: To explore undocumented migrants' mental healthcare needs
      and more specifically to explore how undocumented adults living in Norway
      perceive psychological distress, to gather insight on their living conditions and
      to explore associated living condition risk factors. BACKGROUND: Undocumented
      migrants are defined both nationally and internationally as an especially
      vulnerable group with regard to their health status, living conditions and
      barriers to access to health care and social welfare. DESIGN: An exploratory
      mixed-methods design using primarily quantitative data with a qualitative
      component was implemented. METHODS: Socio-demographic data on 90 undocumented
      migrants were obtained, and self-report questionnaire on psychological distress
      was completed, supplemented by qualitative data obtained through interviews.
      RESULTS: The level of psychological distress was extremely high in our group of
      undocumented migrants. Leaving their home country because of war or persecution,
      economic strain, homelessness, hunger and having experienced abuse was
      significantly positively associated with psychological distress. Contrary to what
      was predicted, having family and work was not significantly associated with the
      reduction of psychological distress. Additional qualitative data indicate that
      having family entails great responsibilities and work implies exploitation to
      such an extent that any potential positive influence this has on mental health,
      such as a sense of belonging and a reasonable standard of living, is outweighed.
      CONCLUSIONS: The high level of psychological distress indicates a need of
      additional diagnostic evaluation and mental health care. The living conditions
      were so marginal that their day-to-day existence was threatened. RELEVANCE TO
      CLINICAL PRACTICE: We recognised a need for an interdisciplinary and dynamic
      approach to mental health care. Undocumented migrants are in need of a minimum of
      psychological and material support assuring basic needs such as shelter and
      appropriate food and access to health care and social welfare.

PMID- 27875008
TI  - Explicit modeling of abiotic and landscape factors reveals precipitation and
      forests associated with aphid abundance.
AB  - Increases in natural or noncrop habitat surrounding agricultural fields have been
      shown to be correlated with declines in insect crop pests. However, these
      patterns are highly variable across studies suggesting other important factors,
      such as abiotic drivers, which are rarely included in landscape models, may also
      contribute to variability in insect population abundance. The objective of this
      study was to explicitly account for the contribution of temperature and
      precipitation, in addition to landscape composition, on the abundance of a
      widespread insect crop pest, the soybean aphid (Aphis glycines Matsumura), in
      Wisconsin soybean fields. We hypothesized that higher soybean aphid abundance
      would be associated with higher heat accumulation (e.g., growing degree days) and
      increasing noncrop habitat in the surrounding landscape, due to the presence of
      the overwintering primary hosts of soybean aphid. To evaluate these hypotheses,
      we used an ecoinformatics approach that relied on a large dataset collected
      across Wisconsin over a 9-year period (2003-2011), for an average of 235 sites
      per year (n = 2,110 fields total). We determined surrounding landscape
      composition (1.5-km radius) using publicly available satellite-derived land cover
      imagery and interpolated daily temperature and precipitation information from the
      National Weather Service COOP weather station network. We constructed linear
      mixed models for soybean aphid abundance based on abiotic and landscape
      explanatory variables and applied model averaging for prediction using an
      information theoretic framework. Over this broad spatial and temporal extent in
      Wisconsin, we found that variation in growing season precipitation was positively
      related to soybean aphid abundance, while higher precipitation during the
      nongrowing season had a negative effect on aphid populations. Additionally, we
      found that aphid populations were higher in areas with proportionally more forest
      but were lower in areas where minor crops, such as small grains, were more
      prevalent. Thus, our findings support our hypothesis that including abiotic
      drivers increases our understanding of crop pest abundance and distribution.
      Moreover, by explicitly modeling abiotic factors, we may be able to explore how
      variable climate in tandem with land cover patterns may affect current and future
      insect populations, with potentially critical implications for crop yields and
      agricultural food webs.

PMID- 27875010
TI  - Nutrients influence the thermal ecophysiology of an intertidal macroalga:
      multiple stressors or multiple drivers?
AB  - Urbanization of coastlines is leading to increased introduction of nutrients from
      the terrestrial environment to nearshore habitats. While such nutrient influxes
      can be detrimental to coastal marine organisms due to increased eutrophication
      and subsequent reduced oxygen, they could also have positive effects (i.e.,
      increased food availability) on species that are nitrogen-limited such as
      macroalgae. Nutrient enrichment in this environment thus has the potential to
      counteract some of the negative impacts of increasing temperatures, at least for
      some species. Characterizing the physiological response of organisms to
      simultaneous changes in multiple drivers such as these is an important first step
      in predicting how global climate change may lead to ecological responses at more
      local levels. We evaluated how nutrient enrichment (i.e., nitrogen availability)
      affected the growth of Fucus vesiculosus, a foundational macroalgal species in
      the North Atlantic rocky intertidal zone, and found that nutrient-enriched algal
      blades showed a significant increase in tissue growth compared to individuals
      grown under ambient conditions. We further quantified net photosynthesis by
      ambient and nutrient-enriched tissues at saturating irradiance over a range of
      temperature conditions (6-30 degrees C). Respiration was unaffected by nutrient
      treatment; however, there was a significant increase in photosynthetic oxygen
      production for nutrient-enriched tissue compared to ambient, but only at elevated
      (>=18 degrees C) temperatures. This study contributes to a growing body of
      literature showing the complexity of responses to changes in multiple drivers,
      and highlights the importance of studying the impacts of global climate change
      within the context of more local environmental conditions.

PMID- 27875009
TI  - 3D printing from MRI Data: Harnessing strengths and minimizing weaknesses.
AB  - : 3D printing facilitates the creation of accurate physical models of patient
      specific anatomy from medical imaging datasets. While the majority of models to
      date are created from computed tomography (CT) data, there is increasing interest
      in creating models from other datasets, such as ultrasound and magnetic resonance
      imaging (MRI). MRI, in particular, holds great potential for 3D printing, given
      its excellent tissue characterization and lack of ionizing radiation. There are,
      however, challenges to 3D printing from MRI data as well. Here we review the
      basics of 3D printing, explore the current strengths and weaknesses of printing
      from MRI data as they pertain to model accuracy, and discuss considerations in
      the design of MRI sequences for 3D printing. Finally, we explore the future of 3D
      printing and MRI, including creative applications and new materials. LEVEL OF
      EVIDENCE: 5 J. Magn. Reson. Imaging 2017;45:635-645.

PMID- 27875011
TI  - Characterization of Tin/Ethylene Glycol Solar Nanofluids Synthesized by
      Femtosecond Laser Radiation.
AB  - Solar energy is available over wide geographical areas and its harnessing is
      becoming an essential tool to satisfy the ever-increasing demand for energy with
      minimal environmental impact. Solar nanofluids are a novel solar receiver concept
      for efficient harvesting of solar radiation based on volumetric absorption of
      directly irradiated nanoparticles in a heat transfer fluid. Herein, the
      fabrication of a solar nanofluid by pulsed laser ablation in liquids was
      explored. This study was conducted with the ablation of bulk tin immersed in
      ethylene glycol with a femtosecond laser. Laser irradiation promotes the
      formation of tin nanoparticles that are collected in the ethylene glycol as
      colloids, creating the solar nanofluid. The ability to trap incoming
      electromagnetic radiation, thermal conductivity, and the stability of the solar
      nanofluid in comparison with conventional synthesis methods is enhanced.

PMID- 27875012
TI  - Growth of nurse prescribing competence: facilitators and barriers during
      education.
AB  - AIMS AND OBJECTIVES: To describe facilitators and barriers in relation to the
      growth of nurse prescribing competence from the perspective of the nurses
      studying in a prescribing programme. BACKGROUND: The number of nurses enrolled in
      a nurse prescribing programme is rapidly increasing in Finland. However, few
      studies on nurse prescribing education are available and therefore research is
      needed, particularly from the point of view of nurses studying in the programme.
      DESIGN: The descriptive, qualitative study used the text of student online
      learning diaries as data during a 14-month prescribing programme. The sample
      consisted of 31 nurses, public health nurses or midwives enrolled in a
      prescribing programme at a university of applied sciences. The data were analysed
      using the inductive analysis method. RESULTS: The growth of nurses' prescribing
      competence was facilitated by learning clinical examination of the patient,
      networking with peers, receiving support from the workplace and supervisors,
      doctors' positive attitude towards nurse prescribing and being able to apply
      competencies directly to nursing practice. The barriers to the growth of nurses'
      prescribing competence were unclear job description, incomplete care plans and
      concerns about how consultation with doctors will be organised and realised.
      CONCLUSIONS: The results show that, for the purpose of developing the new role
      and position of nurse prescribers, educators and nursing managers must invest
      more in staff awareness of nurse prescribing education and also offer more
      support to nurse prescribers in their workplaces. RELEVANCE TO CLINICAL PRACTICE:
      The results of this study can be used especially in countries where nurse
      prescribing education is only in the process of being planned or has just been
      started. Heads of nursing and educators in prescribing education will benefit
      from the results when creating expanded job descriptions for nurses and
      supporting networking between students during the period of training.

PMID- 27875013
TI  - 'Intensive care unit survivorship' - a constructivist grounded theory of
      surviving critical illness.
AB  - AIMS AND OBJECTIVES: To theorise intensive care unit survivorship after a
      critical illness based on longitudinal qualitative data. BACKGROUND:
      Increasingly, patients survive episodes of critical illness. However, the short-
      and long-term impact of critical illness includes physical, psychological, social
      and economic challenges long after hospital discharge. An appreciation is
      emerging that care needs to extend beyond critical illness to enable patients to
      reclaim their lives postdischarge with the term 'survivorship' being increasingly
      used in this context. What constitutes critical illness survivorship has, to
      date, not been theoretically explored. DESIGN: Longitudinal qualitative and
      constructivist grounded theory. Interviews (n = 46) with 17 participants were
      conducted at four time points: (1) before discharge from hospital, (2) four to
      six weeks postdischarge, (3) six months and (4) 12 months postdischarge across
      two adult intensive care unit setting. METHOD: Individual face-to-face
      interviews. Data analysis followed the principles of Charmaz's constructivist
      grounded theory. 'Intensive care unit survivorship' emerged as the core category
      and was theorised using concepts such as status passages, liminality and
      temporality to understand the various transitions participants made postcritical
      illness. FINDINGS: Intensive care unit survivorship describes the unscheduled
      status passage of falling critically ill and being taken to the threshold of life
      and the journey to a life postcritical illness. Surviving critical illness goes
      beyond recovery; surviving means 'moving on' to life postcritical illness.
      'Moving on' incorporates a redefinition of self that incorporates any lingering
      intensive care unit legacies and being in control of one's life again. RELEVANCE
      TO CLINICAL PRACTICE: For healthcare professionals and policymakers, it is
      important to realise that recovery and transitioning through to survivorship
      happen within an individual's time frame, not a schedule imposed by the
      healthcare system. Currently, there are no care pathways or policies in place for
      critical illness survivors that would support intensive care unit survivors and
      their families in the transitions to survivorship.

PMID- 27875014
TI  - A Viologen-Perylenediimide Conjugate as an Efficient Base Sensor with
      Solvatochromic Property.
AB  - A viologen-perylenediimide conjugate, denoted PDEV, is prepared for efficient
      base sensing. The conjugate shows solvatochromic behavior as well. The base
      sensitivity of viologen is purposefully coupled with the emission property of
      perylenediimide (PDI) to lower the detection limit. PDEV shows base-sensing
      ability at the ppb level, which is at least three orders of magnitude lower than
      those of previously reported sensors. The probe is sensitive toward solvent
      polarity and generates different shades of colors according to the polarity of
      the medium (solvent). The photophysical properties show a linear correlation with
      the solvent polarity, and this makes it an efficient solvatochromic agent. On the
      other hand, the generation of viologen radical cations by bases affects the
      aggregation and consequently the absorption and emission behavior of the PDI
      core. The effect of bases can also be visualized, because the probe generates
      different colors in the presence of bases, both under normal and under UV light.
      Organic amines can be detected even in the crystalline state, since the dark red
      color of the PDEV crystals changes to purple in a reversible fashion on exposure
      to amine vapors. An easy and practical paper-based tool created by using the
      probe can efficiently be used to detect solvent polarity and presence of bases
      optically.

PMID- 27875015
TI  - Getting evidence-based pressure ulcer prevention into practice: a process
      evaluation of a multifaceted intervention in a hospital setting.
AB  - AIMS AND OBJECTIVES: To describe registered nurses', assistant nurses' and first
      line managers' experiences and perceptions of a multifaceted hospital setting
      intervention focused on implementing evidence-based pressure ulcer prevention.
      BACKGROUND: Pressure ulcer prevention is deficient. Different models exist to
      support implementation of evidence-based care. Little is known about
      implementation processes. DESIGN: A descriptive qualitative approach. METHOD:
      Five focus-group nurse interviews and five individual first-line manager
      interviews were conducted at five Swedish hospital units. Qualitative content
      analysis was used. RESULT: The findings support that the intervention and the
      implementation process changed the understanding and way of working with pressure
      ulcer prevention: from treating to preventing. This became possible as 'Changed
      understanding enables changed actions - through one's own performance and
      reflection on pressure ulcer prevention'. Having a common outlook on pressure
      ulcer prevention, easy access to pressure-reducing equipment, and external and
      internal facilitator support were described as important factors for changed
      practices. Bedside support, feedback and discussions on current results increased
      the awareness of needed improvements. CONCLUSION: The multifaceted intervention
      approach and the participants' positive attitudes seemed to be crucial for
      changing understanding and working more preventatively. The strategies used and
      the skills of the facilitators need to be tailored to the problems surrounding
      the context. Feedback discussions among the staff regarding the results of the
      care provided also appear to be vital. RELEVANCE TO CLINICAL PRACTICE: It is
      crucial that dedicated facilitators are involved to promote the implementation
      process. A preventative mindset should be strived for. Creating an implementation
      plan with an outcome and a process evaluation should be emphasised. It is
      important to give the staff regular feedback on the quality of care and on those
      occasions allocate time for discussion and reflection.

PMID- 27875017
TI  - Gum chewing combined with oral intake of a semi-liquid diet in the postoperative
      care of patients after gynaecologic laparoscopic surgery.
AB  - AIM AND OBJECTIVES: To evaluate the effects of gum chewing combined with a semi
      liquid diet on patients after gynaecologic laparoscopic surgery. BACKGROUND:
      Previous studies suggested that chewing gum before traditional postoperative care
      promotes the postoperative recovery of bowel motility and function after open and
      laparoscopic surgery. However, gum chewing combined with a semi-liquid diet has
      not been reported in postoperative care of patients following gynaecologic
      laparoscopic surgery. DESIGN: A prospective randomised study. METHODS: Total 234
      patients were randomly assigned after elective gynaecologic laparoscopic surgery
      to a gum chewing and semi-liquid diet group, a semi-liquid only diet group or a
      liquid diet group. The gum chewing and semi-liquid diet group chewed sugar-free
      gum with an oral intake of a semi-liquid diet six hours postoperatively. The semi
      liquid only diet and liquid diet groups received a semi-liquid diet or a liquid
      diet, respectively. The time to first bowel sounds, time to first regular
      postoperative bowel sounds, time to first passage of flatus, time to first
      defecation, serum gastrin and incidences of hunger, nausea, vomiting and
      abdominal distension were recorded. Hunger and gastrointestinal sensations were
      assessed using a four-point scale. Serum gastrin was assayed pre- and
      postoperatively using a gastrin radioimmunoassay kit. RESULTS: The gum chewing
      and semi-liquid diet group had first bowel sounds, first regular bowel sounds,
      first passage of flatus and first defecation earlier than the semi-liquid only
      and liquid groups. Increased serum gastrin was observed in the gum chewing and
      semi-liquid diet group. Incidences of nausea, vomiting and abdominal distention
      were not significantly different between these groups. CONCLUSION: Chewing gum
      combined with an oral intake of a semi-liquid diet is safe and accelerates the
      postoperative recovery of bowel function. It might be recommended as a better
      postoperative care regimen for patients after gynaecologic laparoscopic surgery.
      RELEVANCE TO CLINICAL PRACTICE: This study developed a new postoperative diet
      regimen to improve the postoperative care of patients undergoing laparoscopic
      gynecologic surgery.

PMID- 27875016
TI  - Cryptococcal infections in solid organ transplant recipients over a 15-year
      period at a state transplant center.
AB  - BACKGROUND: The aim of this research paper was to determine the incidence, risk
      factors, and clinical outcome of solid organ transplant (SOT) recipients
      diagnosed and treated for cryptococcosis at our institution. METHODS:
      Retrospective analysis of all patients with SOT diagnosed and treated for
      cryptococcal infection occurring between January 2001 and December 2015. RESULTS:
      Of 102 patients diagnosed with cryptococcal infection, 23 were SOT recipients.
      Renal transplant accounted for 22/23 cases, of which 13 had meningitis. The
      annual incidence of infection has risen significantly, and is now greater than
      2/1000 prevalent renal transplant recipients. As expected, biochemical factors
      associated with meningitis include lower glucose on cerebrospinal fluid (CSF)
      analysis, median 2.4 vs 4.5 mmol/L (P=.02); CSF white blood cell median 50 vs
      1/MUL (P<.001); CSF protein, median 950 vs 335 mg/L (P=.04). Serum cryptococcal
      antigen titers were higher in the meningitis cohort, median 512 vs 32 (P=.03).
      Clinically, headache on admission (odds ratio: 9 [1.29-63.03], P=.03) and a
      prolonged length of stay (median of 36 vs 13 days) in the meningitis cohort
      (P=.02) were significant. CONCLUSION: Cryptococcal infection in SOT recipients
      remains rare; however, there has been a marked increase in cases since 2014. This
      study reveals a need for increased vigilance for a potential emerging infectious
      disease. It furthermore highlights the need for ongoing research to further aid
      early diagnosis, prognostication, management, and screening cost-effectiveness.

PMID- 27875018
TI  - The process and challenges of obtaining and sustaining clinical placements for
      nursing and allied health students.
AB  - AIMS AND OBJECTIVES: To describe the process and challenges from a project that
      aimed to develop processes, source new placements and place students primarily in
      the discipline of nursing, but also occupational therapy, physiotherapy,
      podiatry, social work, and speech therapy. BACKGROUND: Clinical experience in
      health facilities is an essential element of health professional education, yet
      globally, there is a lack of clinical placements to meet demands. Educational
      providers are seeking placements in nontraditional facilities, yet little has
      been reported on the challenges in the process of procuring clinical placements.
      DESIGN: The project used a descriptive approach within a quality implementation
      framework. METHODS: The project was guided by the quality implementation
      framework that included four critical steps: considerations of the host setting,
      structuring the implementation, supporting the implementation and improving
      future applications. RESULTS: A total of 115 new student placements were
      finalised across six health disciplines, including elderly care, nongovernment
      organisations and general practice. Sixty-two nursing students were placed in the
      new placements during the project. Challenges included communication, the time
      consuming nature of the process and 'gatekeeping' blocks to obtaining placements.
      Recommendations included the importance of personal interaction in developing and
      maintaining relationships, and the need for clear communication processes and
      documentation. Potential areas for research are also given. CONCLUSIONS: There is
      great potential for growth in establishing new placements outside the traditional
      placement facilities for nursing and allied health and for expanding already
      existing nonhospital placements. RELEVANCE TO CLINICAL PRACTICE: Clinical
      professional experiences are essential to any nursing or allied health programme.
      There is an increasing demand for, and global lack of, clinical placements for
      nursing and allied health students. The results provide nursing and allied health
      educators and managers a framework for planning clinical placement procurement,
      and assisting in decision-making and developing strategies and processes for
      practice.

PMID- 27875020
TI  - Linking otolith microchemistry and dendritic isoscapes to map heterogeneous
      production of fish across river basins.
AB  - Production patterns of highly mobile species, such as anadromous fish, often
      exhibit high spatial and temporal heterogeneity across landscapes. Such
      variability is often asynchronous in time among habitats, which stabilizes
      production at aggregate scales of complexity. Reconstructing production patterns
      explicitly in space and time across multiple scales, however, remains difficult
      but is important for prioritizing habitat conservation. This is especially true
      for fishes inhabiting river basins due to long-range dispersal, high mortality at
      early life stages, complex population structure and elusive life history
      variation. We develop a new approach for mapping production patterns of Pacific
      salmon across a large river basin by integrating otolith microchemistry and
      dendritic isoscape models. The geographically continuous Bayesian assignment
      framework presented here yielded high accuracies (>90%) and relatively high
      precisions (precisions <4%; i.e., assignment areas of <530 river km of the 13 100
      km total river length) when used to determine the natal source of known-origin
      juvenile Chinook salmon captured throughout the study region. Integrating these
      methods enabled us to base estimates of provenance and habitat use of individuals
      on a per location basis using strontium isotopic data throughout the continuous
      spatial domain of a river network. Such a framework provides substantial
      advantages over the more common nominal approach to employing otolith
      microchemistry to reconstruct movement patterns of fish. In doing so, we
      reconstructed the spatial production patterns of adult Chinook salmon returning
      to a large watershed in Bristol Bay, Alaska and illustrate the power of such an
      approach to conservation efforts.

PMID- 27875019
TI  - Generation of targeted mutant rice using a CRISPR-Cpf1 system.
AB  - CRISPR-Cpf1 is a newly identified CRISPR-Cas system, and Cpf1 was recently
      engineered as a molecular tool for targeted genome editing in mammalian cells. To
      test whether the engineered CRISPR-Cpf1 system could induce the production of
      rice mutants, we selected two genome targets in the OsPDS and OsBEL genes. Our
      results show that both targets could be efficiently mutated in transgenic rice
      plants using CRISPR-Cpf1. We found that pre-crRNAs with a full-length direct
      repeat sequence exhibited considerably increased efficiencies compared with
      mature crRNAs. In addition, the specificity and transmission of the mutation were
      investigated, and the behaviours of crRNA-Cpf1-induced plant targeted genome
      mutagenesis were assessed. Taken together, our results indicate that CRISPR-Cpf1
      expression via stable transformation can efficiently generate specific and
      heritable targeted mutations in rice and thereby constitutes a novel and
      important approach to specific and precise plant genome editing.

PMID- 27875021
TI  - Lifestyle and bowel movements in school children: Results from the Toyama Birth
      Cohort Study.
AB  - BACKGROUND: Constipation is a prevalent health disorder. There have been few
      epidemiological surveys on constipation in Japanese children. The aim of this
      study was to evaluate the prevalence of non-daily bowel movements (BM) and
      irregular BM among children and to identify modifiable lifestyle factors relevant
      to bowel habits. METHODS: Subjects were from the Toyama Birth Cohort Study in
      Japan. A total of 7762 children aged 9-10 years were investigated via
      questionnaire in 1999. We evaluated bowel habit and the relationship between
      lifestyle and BM. Non-daily BM and totally irregular BM were defined as dependent
      variables in the present study. RESULTS: Non-daily BM were reported by 21.8% of
      boys and by 31.6% of girls, while 10.6% of boys and 18.3% of girls had totally
      irregular BM. Non-daily BM were significantly associated with skipping breakfast
      (OR, 1.23), slow eating (OR, 1.13), physical inactivity (OR, 1.50) and late wake
      up (OR, 1.29). Totally irregular BM were significantly correlated with skipping
      breakfast (OR, 1.30), slow eating (OR, 1.41), physical inactivity (OR, 1.27),
      long TV viewing (OR, 1.52), late bedtime (OR, 1.43), and short sleep duration
      (OR, 1.33). More girls had non-daily and totally irregular BM than boys, and
      these sex differences were not reduced after adjusting for lifestyle variables.
      CONCLUSIONS: Non-daily and totally irregular BM are common in children, and there
      are many relevant lifestyle factors. Establishing regular lifestyle habits may
      lessen constipation.

PMID- 27875022
TI  - A comparison of left and right atrial fibroblasts reveals different collagen
      production activity and stress-induced mitogen-activated protein kinase
      signalling in rats.
AB  - AIM: Atrial fibrosis plays a pivotal role in the pathophysiology of heart failure
      (HF). The left atrium (LA) experiences greater fibrosis than the right atrium
      (RA) during HF. It is not clear whether LA cardiac fibroblasts contain
      distinctive activities that predispose LA to fibrosis. METHODS: LA and RA
      fibrosis were evaluated in healthy and isoproterenol-induced HF Sprague Dawley
      rats. Rat LA and RA primary isolated fibroblasts were subjected to proliferation
      assay, oxidative stress assay, cell migration analysis, collagen measurement,
      cytokine array and Western blot. RESULTS: Healthy rat LA and RA had a similar
      extent of collagen deposition. HF significantly increased fibrosis to a greater
      severity in LA than in RA. Compared to isolated RA fibroblasts, the in vitro
      experiments showed that isolated LA fibroblasts had higher oxidative stress and
      exhibited higher collagen, transforming growth factor-beta1, connective tissue
      growth factor production and less vascular endothelial growth factor (VEGF)
      production, but had similar migration, myofibroblast differentiation and
      proliferation activities. VEGF significantly increased the collagen production
      ability of LA fibroblasts, but not RA fibroblasts. LA fibroblasts had more
      phosphorylated ERK1/2 and P38 expression. ERK inhibitor (PD98059, 50 MUmol L-1 )
      significantly attenuated collagen production and increased VEGF production in RA
      fibroblasts but not in LA fibroblasts. P38 inhibitor (SB203580, 30 MUmol L-1 )
      significantly attenuated collagen production in LA fibroblasts but not in RA
      fibroblasts. P38 inhibitor also significantly increased VEGF production in RA and
      LA fibroblasts. CONCLUSIONS: Differences in profibrotic activity between LA and
      RA fibroblasts may be caused by different responses to mitogen-activated protein
      kinase signalling.

PMID- 27875024
TI  - The Feasibility of Energy Extraction from Acidic Wastewater by Capacitive Mixing
      with a Molecular-Sieving Carbon Electrode.
AB  - Capacitive mixing is a newly emerging technique for the production of renewable
      energy from differences in salinity, usually of wastewater streams. The method is
      based on the controlled mixing of two streams with different salt concentrations,
      which are alternatingly brought into contact with precharged porous electrodes,
      thus taking advantage of the fact that modification of the electrical double
      layer of the electrodes results in changes in the solution salinity. Usually, the
      renewable energy resources are seawater and river water streams. Here, we
      demonstrated that electrical energy can be extracted by capacitive mixing of
      acidic wastewater and seawater. This concept is proven by the use of proton
      selective carbon as the cation-capturing electrode, fabricated by carbonization
      of cellulose filter paper followed by mild activation in concentrated nitric
      acid. Considerable energy extraction was demonstrated even if the concentration
      of the NaCl solution was tenfold higher than that of the acidic solution.

PMID- 27875023
TI  - Myxochelin-Inspired 5-Lipoxygenase Inhibitors: Synthesis and Biological
      Evaluation.
AB  - A total of 48 analogues of the natural product myxochelin A were prepared and
      evaluated for their inhibitory effects on human 5-lipoxygenase in both cell-free
      and cell-based assays. Structure-activity relationship analysis revealed that the
      secondary alcohol function and only chiral center of myxochelin A is not required
      for biological activity. By expanding the diaminoalkane linker of the two
      aromatic residues it was possible to generate a myxochelin derivative with
      superior activity against 5-lipoxygenase in intact cells.

PMID- 27875025
TI  - Adherence and barriers to hyperinsufflation in children with congenital muscular
      dystrophy.
AB  - BACKGROUND: Congenital muscular dystrophy (CMD) is a rare, inherited
      neuromuscular disease characterized by progressive muscle weakness, thoracic
      insufficiency, and ultimately respiratory failure. Adherence to respiratory
      therapies in children with neuromuscular disorders is unknown. This study
      examined the multimodal assessment of adherence and barriers to 15 min, twice
      daily hyperinsufflation in children with CMD. Adherence was hypothesized to be
      greater than 50% and discomfort, embarrassment, and difficulty finding time were
      hypothesized to be barriers. METHODS: Participants included 18 children with CMD.
      Personalized hyperinsufflation settings were determined based on pressure-volume
      measurements at each study visit. Adherence was measured by a daily phone diary
      (DPD) and by electronic data download from the hyperinsufflation device. The DPD
      was conducted twice over a 48-hr period to capture a weekend and weekday, with
      the goal being 60 min of hyperinsufflation over the 48 hr (100% adherence). The
      hyperinsufflation objective electronic data reflected daily use of
      hyperinsufflation for the same 48-hr period. Data from DPD and the corresponding
      hyperinsufflation device data were used for analyses. RESULTS: Adherence to
      hyperinsufflation was 40% via DPD and 44% for electronic data, with strong
      convergence between methods (r = 0.75, P < 0.001). Surprisingly, 53% of
      participants reported no barriers despite low adherence. Social distractions and
      family obligations were identified as barriers. There were no differences in
      adherence between those who did and did not endorse barriers to hyperinsufflation
      (DPD: t(13) = 0.44, P = n.s.; hyperinsufflation device: t(13) = -0.23, P = n.s.).
      CONCLUSION: Adherence to hyperinsufflation is a significant problem in children
      with CMD and families have difficulty identifying adherence barriers. An
      important next step is to encourage open dialog around adherence barriers and
      promote adherence behaviors via intervention. Pediatr Pulmonol. 2017; 52:939-945.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27875026
TI  - Disseminated BCG pneumonitis revealing severe combined immunodeficiencyxs in
      CHARGE syndrome.
AB  - CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development,
      genital hypoplasia, and ear anomalies/deafness) syndrome is a rare genetic
      disorder caused by CHD7 mutation and is related to immunodeficiency. A 6-month
      old girl with right lung agenesis, congenital heart defects, and ear anomalies
      developed repeated and serious respiratory infection for a short period. She was
      clinically diagnosed with typical CHARGE syndrome with severe combined
      immunodeficiency (T-, B+, NK-); however, CHD7 mutation was not detected.
      Disseminated BCG infection did not resolve despite administration of anti
      tuberculosis drugs and intravenous immune globulins, and she subsequently died of
      acute respiratory distress syndrome. Pediatr Pulmonol. 2017;52:E4-E6. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27875027
TI  - Tribology of flexible and sliding spinal implants: Development of experimental
      and numerical models.
AB  - New fusionless devices are being developed to get over the limits of actual
      spinal surgical treatment, based on arthrodesis. However, due to their
      recentness, no standards exist to test and validate those devices, especially
      concerning the wear. A new tribological first approach to the definition of an in
      vitro wear protocol to study wear of flexible and sliding spinal devices is
      presented in this article, and was applied to a new concept. A simplified
      synthetic spine portion (polyethylene) was developed to reproduce a simple supra
      physiological spinal flexion (10 degrees  between two vertebrae). The device
      studied with this protocol was tested in wet environment until 1 million cycles
      (Mc). We obtained an encouraging estimated wear volume of same order of magnitude
      compared to similar devices. An associated finite element (FE) numerical model
      has permitted to access contact information and study the effect of misalignment
      of one screw. First results could point out how to improve the design and suggest
      that a vertical misalignment of a screw (under or over-screwing) has more impact
      than a horizontal one. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater, 106B: 104-111, 2018.

PMID- 27875028
TI  - Congenital malformations in offspring of women with a history of malignancy.
AB  - BACKGROUND: Survival after malignancy has increased and the question of risks,
      including risk for congenital malformations for the offspring of these women has
      become important. Data on congenital malformations in such offspring are limited.
      METHODS: We compared congenital malformation in offspring, born 1994 to 2011 of
      women with a history of malignancy (at least 1 year before delivery) with all
      other offspring. Adjustment for confounders was mainly made by Mantel-Haenszel
      methodology. Data were obtained by linkage between Swedish national health
      registers. RESULTS: We identified 71,954 (4.1%) infants with congenital
      malformation, of which 47,081 (2.7%) were relatively severe (roughly
      corresponding to major malformation). Among 7284 infants to women with a history
      of malignancy 204 relatively severe malformations were found (2.8%; odds ratio
      [OR] = 1.04; 95% confidence interval [CI], 0.91-1.20). After in vitro
      fertilization, the risk of a relatively severe malformation was significantly
      increased in women without a history of malignancy (OR = 1.31; 95% CI, 1.24-1.38)
      and still more in women with such a history (risk ratio = 1.85; 95% CI, 1.08
      2.97). However, there were no significant differences neither, for any
      malformations (OR = 1.04; 95% CI, 0.92-1.16) nor for relatively severe
      malformations (OR = 1.04; 95% CI, 0.91-1.20), when comparing offspring only after
      maternal history of malignancy. CONCLUSION: No general increase in malformation
      rate was found in infants born to women with a history of malignancy. A
      previously known increased risk after in vitro fertilization was verified and it
      is possible that this risk is further augmented among infants born of women with
      a history of malignancy. Birth Defects Research 109:224-233, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27875029
TI  - Decreased Activity and Genetic Polymorphisms of CYP2C19 in Behcet's Disease.
AB  - Behcet's disease (BD) is a systemic autoimmune disorder. Cytochrome P450 enzymes
      (CYPs) are responsible for various drug metabolism reactions as well as those of
      endogenous substances which may be associated with autoimmune disease
      susceptibility. Recently, we reported that in patients with BD, CYP2C9 seems to
      be down-regulated due to inflammation. In the same Turkish patients with BD, we
      investigated whether also CYP2C19 activity is decreased. Lansoprazole (30 mg) was
      given as a probe drug to evaluate CYP2C19 activity in 59 patients with BD and 27
      healthy control volunteers. An HPLC method was used to determine plasma
      lansoprazole and its metabolite, 5-hydroxy lansoprazole, concentrations. The
      genotyping for CYP2C19 *2, *3 and *17 polymorphisms was made using PCR-RFLP. The
      median lansoprazole/5-hydroxy lansoprazole metabolic ratio (MR) in patients with
      BD was 2.6-fold higher as compared to the healthy control group (p = 0.001, 22.6
      (1.3-26) and 8.8 (0.5-140) as median and range, respectively). The CYP2C19*17*17
      genotype frequency was found to be significantly less in the BD group as compared
      to the healthy controls (1.7% versus 14.8% in controls, p = 0.01). Additionally,
      colchicine treatment did not affect the CYP2C19 enzyme activity in six patients
      (p = 0.43). In conclusion, the patients with BD had lower CYP2C19 enzyme activity
      and lower frequency of the CYP2C19*17 allele as compared to those of the healthy
      controls. Further studies are warranted on the mechanisms underlying this
      relation. This study should also be applied to other autoimmune diseases
      similarly characterized by local or systemic inflammation.

PMID- 27875030
TI  - The differentiation of oral soft- and hard tissues using laser induced breakdown
      spectroscopy - a prospect for tissue specific laser surgery.
AB  - Compared to conventional techniques, Laser surgery procedures provide a number of
      advantages, but may be associated with an increased risk of iatrogenic damage to
      important anatomical structures. The type of tissue ablated in the focus spot is
      unknown. Laser-Induced Breakdown-Spectroscopy (LIBS) has the potential to gain
      information about the type of material that is being ablated by the laser beam.
      This may form the basis for tissue selective laser surgery. In the present study,
      7 different porcine tissues (cortical and cancellous bone, nerve, mucosa, enamel,
      dentine and pulp) from 6 animals were analyzed for their qualitative and
      semiquantitative molecular composition using LIBS. The so gathered data was used
      to first differentiate between the soft- and hard-tissues using a Calcium-Carbon
      emission based classifier. The tissues were then further classified using
      emission-ratio based analysis, principal component analysis (PCA) and linear
      discriminant analysis (LDA). The relatively higher concentration of Calcium in
      the hard tissues allows for an accurate first differentiation of soft- and hard
      tissues (100% sensitivity and specificity). The ratio based statistical
      differentiation approach yields results in the range from 65% (enamel-dentine
      pair) to 100% (nerve-pulp, cancellous bone-dentine, cancellous bone-enamel pairs)
      sensitivity and specificity. Experimental LIBS measuring setup.

PMID- 27875031
TI  - Prevalence of neural tube defects in a rural area of north india from 2001 to
      2014: A population-based survey.
AB  - BACKGROUND: Neural tube defects (NTDs) are one of the commonest birth defects.
      There was paucity of community-based data on occurrence of NTDs in India,
      especially from rural parts of the country. Against this background, the current
      study was carried out with main objectives to determine the prevalence of NTDs
      and its specific types (anencephaly, spina bifida and encephalocele) in a rural
      community setting over the time period 2001 to 2014. METHODS: This was a
      community-based cross-sectional study carried out in 28 villages of Ballabgarh
      Tehsil of Faridabad district in north India (population ~ 96,000). A household
      survey was undertaken by trained multi-purpose workers who enquired ever-married
      women about history of conception with outcome as NTD during the study period.
      The probable case of NTD was determined using a colored pictorial card with
      photographs of different types of NTDs. These cases were confirmed by doctors.
      RESULTS: A total of 26,946 live births occurred during the years 2001 to 2014. A
      total of 140 confirmed cases of NTDs were identified. The live birth prevalence
      of NTDs was 24.1 per 10,000 live births (95% confidence interval, 18.8-30.6). The
      birth prevalence of NTDs for the years 2008 to 2014 was 50.8 (95% confidence
      interval, 39.9-63.8) per 10,000 live and stillbirths. The most common type of NTD
      was found to be spina bifida followed by anencephaly and encephalocele.
      CONCLUSION: We found high prevalence of NTDs in rural community settings from
      north India for years 2001 to 2014.Birth Defects Research 109:203-210, 2017.(c)
      2016 Wiley Periodicals, Inc.

PMID- 27875032
TI  - Management of renal failure in end-stage liver disease: A critical appraisal.
AB  - Renal failure is a late consequence of end-stage liver disease (ESLD). Even with
      liver transplantation, pretransplant renal impairment remains a strong predictor
      of posttransplant mortality. This review seeks to summarize and critically
      appraise common therapies used in this setting, including pharmacologic agents,
      procedures (transjugular intrahepatic portosystemic shunt, renal replacement
      therapy), and simultaneous liver-kidney transplantation. More experimental
      extracorporal modalities, eg, albumin dialysis or bioartificial livers, will not
      be discussed. A brief discussion on the definition and pathophysiologic
      underpinnings of renal failure in ESLD will be held at the beginning to lay the
      groundwork for the main section. Liver Transplantation 22 1710-1719 2016 AASLD.

PMID- 27875033
TI  - Comparison of preoperative hair removal methods for the reduction of surgical
      site infections: a meta-analysis.
AB  - AIMS AND OBJECTIVES: To evaluate the efficacy of different methods of
      preoperative hair removal in reducing surgical site infections. BACKGROUND:
      Surgical site infections are a major source of morbidity and prolonged
      hospitalisation following surgery. However, there is a lack of data regarding the
      impact of different preoperative hair removal techniques on the incidence of
      surgical site infections. DESIGN: A systematic literature review and meta
      analysis. METHODS: Randomised controlled trials and controlled clinical trials
      reporting the impact of different methods of preoperative hair removal on
      reducing surgical site infections were collected through databases, including the
      Cochrane Library, Joanna Briggs Institute Library, PubMed, Elsevier, EMBASE,
      Nursing Consult, China Biology Medicine disc, China National Knowledge
      Infrastructure and Wanfang data. The articles were published from 1 January 1990
      15 March 2016. Meta-analyses were conducted with review manager version 5.0.
      RESULTS: Fourteen trials were included (16 comparisons) in the review, including
      11 randomised controlled trials and three controlled clinical trials.
      Interventions in the studies were shaving, clipping, no hair removal and the use
      of depilatory cream. The meta-analyses included 7278 patients, from 10 countries.
      Nine studies compared shaving with no hair removal, four studies compared shaving
      with clipping, two studies compared shaving with depilatory cream, and one study
      compared clipping with no hair removal. No significant differences in the
      frequency of surgical site infections were observed between any of the methods
      assessed. CONCLUSIONS: No significant differences between shaving, clipping, no
      hair removal and depilatory cream were observed in the frequency of surgical site
      infections. RELEVANCE TO CLINICAL PRACTICE: Preoperative hair removal should be
      avoided unless necessary. When it is necessary to remove hair, the existing
      evidence suggests that clipping is more effective in reducing surgical site
      infections than shaving or depilatory cream.

PMID- 27875034
TI  - Risk factors of post-traumatic stress symptoms in patients with cancer.
AB  - AIMS AND OBJECTIVES: To determine the level of post-traumatic stress symptoms and
      to identify demographics, disease history and clinical symptoms that were
      associated with post-traumatic stress symptoms among patients with
      gynaecological, breast or colorectal cancer in Taiwan. BACKGROUND: Literature
      indicated that 7.3-35.2% of patients with cancer had experienced level of post
      traumatic stress symptoms. However, the post-traumatic stress symptoms among
      patients with cancer in Taiwan was not documented. DESIGN: A cross-sectional
      study. METHODS: A total of 347 participants recruited from two general hospitals
      in southern Taiwan. They completed the Chinese version of Davidson Trauma Scale
      and a profile describing their demographics and clinical symptoms. Disease
      history was collected from medical records. RESULTS: Approximately 21.6% of
      participants reported higher score on Chinese version of Davidson Trauma Scale
      (Mean +/- SD = 22.85 +/- 24.12). The top four scores on Chinese version of
      Davidson Trauma Scale were painful memories, insomnia, shortened lifespan and
      flashbacks. The risk factors of post-traumatic stress symptoms were suicidal
      intention (OR = 2.29, 95% CI = 1.86-2.82), chemotherapy (OR = 2.13, 1.18-3.84),
      metastasis (OR = 2.07, 1.29-3.34), cancer-specific symptoms (OR = 1.21, 1.15
      1.27) and high education (OR = 1.75, 1.10-2.78). CONCLUSION: To prevent post
      traumatic stress symptoms, patients with cancer should be routinely screened by
      psychiatrists for post-traumatic stress symptoms, for ongoing symptom control and
      suicidal intention. Patients with cancer who are at risk of suicidal behaviour
      should be enrolled in suicide prevention programmes. RELEVANCE TO CLINICAL
      PRACTICE: Nurses need to assess post-traumatic stress symptoms of patients with
      cancer, particularly those who with high education, suffered from complications
      of chemotherapy, metastasis and cancer-specific symptoms and suicidal intention.

PMID- 27875035
TI  - Mothers' experience of not breastfeeding in a breastfeeding culture.
AB  - AIMS AND OBJECTIVES: To describe women's experience of not breastfeeding in a
      breastfeeding culture. BACKGROUND: Breastfeeding represents a fundamental
      cultural value in Norway and many other countries, and a mother may often have
      intense emotions about breastfeeding her child. Political and health authorities
      in many countries have given high priority to encourage breastfeeding among
      mothers. However, breastfeeding can be challenging and sometimes affects mothers'
      mental health and the joy of interaction. DESIGN: Qualitative design. METHODS:
      Individual semistructured interviews with 12 mothers. Qualitative content
      analysis was used to analyse the interviews. RESULTS: Three main categories
      emerged from the data: (1) desire to adapt to Norwegian culture, (2) feeling as
      though one was breaking the law and (3) lack of and unbalanced information. The
      mothers in this study wanted to breastfeed, both to do the best for their child
      and to fulfil cultural expectations. They knew about the advantages of
      breastfeeding. When breastfeeding was stopped, they needed social support because
      they felt it was difficult to do the opposite of what was most common in the
      culture. CONCLUSION: Healthcare workers should consider the mother's individual
      situation when providing breastfeeding guidance. Information about the advantages
      should be adequately balanced and nuanced to prevent shame and guilt. Healthcare
      workers should have sufficient knowledge about how to ensure that infant formula
      is used correctly. RELEVANCE TO CLINICAL PRACTICE: Healthcare workers should pay
      attention to the mother if she has limited social support, and they should
      organise peer support. Healthcare workers must ensure that mothers get balanced
      information about the benefits of breastfeeding and about the differences between
      breastmilk and infant formula. To ensure that infant formula is used correctly
      and to reduce stigma, healthcare workers should have sufficient knowledge about
      formula feeding and health authorities could provide information about how to
      prepare infant formula.

PMID- 27875036
TI  - Drug loaded nanoparticle coating on totally bioresorbable PLLA stents to prevent
      in-stent restenosis.
AB  - Biodegradable polymer poly (dl-lactide) (PDLLA) has been used as drug coating
      material for drug-eluting stents due to its excellent biocompatibility and
      sustained drug release ability. However, the uniform thin layer drug eluting
      coating on a stent not only inhibits the blood vessel's smooth muscle cell
      overgrowth but also delay the endotheliation process which is often associated
      with the occurrence of acute thrombosis. Therefore, in this study, we developed a
      novel coating method using PDLLA nanoparticles (NPs) as a coating to overcome
      this issue. The average 300 nm sized sirolimus-loaded PDLLA nanoparticles were
      prepared by a conventional emulsion solvent evaporation method. A low temperature
      plasma polymerization technology to graft hydrophilic polymers on to poly (l
      lactide) stent was used to increase the surface coating efficiency of
      nanoparticles on the stent. Results showed that sirolimus-loaded nanoparticles
      can be successfully coated on to the stents with sustained drug release
      properties. In vitro cell culture study showed the drug loaded nanoparticle
      coating effectively inhibited the proliferation of smooth muscle cells while
      still allowed a faster proliferation of endothelial cells, suggesting that the
      new NP coated bioresorbable stents have the potential to reduce both the
      occurrence of in-stent restenosis and acute thrombosis. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 88-95, 2018.

PMID- 27875037
TI  - Preparation of chitosan/amino multiwalled carbon nanotubes nanocomposite beads
      for bilirubin adsorption in hemoperfusion.
AB  - Chitosan-carbon nanotube composite beads combines the advantages of chitosan in
      forming a stable biocompatible framework and carbon nanotube that provide
      nanometer effects (high strength and high specific surface area etc.). In this
      study, chitosan/amino multiwalled carbon nanotubes (CS/AMWCNT) composite beads
      was prepared by phase-inversion method, in which CS and AMWCNT was crosslinked by
      ethylene glycol diglycidyl ether (EGDE). The CS/AMWCNT nanocomposite beads
      produced has been characterized by BET, SEM, TGA, and Raman spectroscopy which
      exhibited enhanced thermal stability due to the incorporation of AMWCNT.
      Mechanical test results showed that mechanical strength of the CS/AMWCNT
      composite beads was significantly enhanced when comparing to unmodified chitosan
      beads, the breakage percentage decreased from 34.1% to 0.67%. The adsorption
      capacity for bilirubin was measured in PBS and BSA solutions, and the CS/AMWCNT
      composite beads with 5 wt% AMWCNT showed much higher adsorption capacity (12.7
      mg/g in PBS and 7.6 mg/g in BSA) to bilirubin than chitosan beads (8.5 mg/g in
      PBS and 4.2 mg/g in BSA). Our nanocomposite beads with excellent
      hemocompatibility has a high potential application in blood purification as an
      efficient adsorbent for bilirubin. (c) 2016 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater, 106B: 96-103, 2018.

PMID- 27875050
TI  - Assessment of Oral Human Papillomavirus Prevalence in a Multi-ethnic Pediatric
      Clinic Population.
AB  - The human papillomavirus (HPV) family has been associated with many cancers,
      including oral cancer. Recent studies have also revealed HPV presence from
      healthy adult and pediatric patient saliva samples, though much less is known
      about the oral prevalence of high-risk HPV in healthy children and adolescents.
      The primary goal of this project was to assess the prevalence of HPV within a
      pediatric dental clinic using non-invasively collected saliva. In brief, saliva
      was collected and DNA isolated to screen for HPV strains HPV6, HPV11, HPV16, and
      HPV18. Screening of these samples (N = 187) revealed 9.2% (n = 19/187) harbored
      one or more HPV strains. Although the proportion of males:females and
      minorities:non-minorities positive for HPV was not statistically significantly
      different from the overall sample, an analysis of age revealed significantly more
      HPV-positive samples were found among the youngest age cohorts (3 to 5 years > 6
      to 11 years > 12 to 17 years). In addition, most samples harbored HPV16 (n =
      13/19 or 68.4%). These findings suggest oral HPV infection may, in fact, be more
      prevalent than previously described, which intimates that knowledge and awareness
      of the potential health effects and benefits of HPV vaccination may be
      appropriate for these patients.

PMID- 27875051
TI  - Clinical Significance of Bis-GMA and HEMA Orthodontic Resins Bonding to Enamel
      and Ceramic Materials.
AB  - The advancement of new ceramic materials for dental crowns has prompted the need
      for improved methods of bonding orthodontic brackets to these surfaces.
      Currently, lithium-disilicate is the primary material being used for anterior
      crowns, while zirconia is the primary material being used in the posterior. The
      purpose of this study was to compare the shear bond strength of HEMA (Assure(r)
      Universal Bonding Resin) and bis-GMA (Assure(r) PLUS All Surface Bonding Resin)
      orthodontic bonding resins on enamel, lithium-disilicate, and zirconia materials.
      Two groups were formed, with three tested surfaces per group (n = 20). The
      categories included premolars, zirconia rods, and lithium-disilicate rods. Group
      1 was treated with Assure, and group 2 was treated with Assure PLUS. Zirconia
      rods (1 cm x 1 cm x 4 cm) were used to represent zirconia crowns, and IPS e.max
      CAD rods (1 cm x 1 cm x 2 cm) were used to represent lithium-disilicate crowns.
      Assure and Assure PLUS bonding agents were applied according to the
      manufacturer's specifications, and standard edgewise universal premolar brackets
      were secured using Light BondTM paste without fluoride. After 24 hours the
      brackets were sheared with a universal testing machine (Instron(r) 5566A) and the
      results were recorded. Data were analyzed using a combination of ANOVA and Tukey
      tests. A P value of less than .05 was considered statistically significant.
      Although group 1 and group 2 gave statistically equivalent results, the authors
      found that the ease of use when applying the group 2 bonding agent made it a
      safer, superior product within the confines of this study. It did not require a 4
      minute hydrofluoric acid-etch and needed half the curing time of the group 1
      agent when bonding to ceramic materials.

PMID- 27875052
TI  - The Role of Academic Institutions in Fostering Interprofessional Educational
      Models.
AB  - Dentistry is much broader than the conditions it treats. In 2014, the Harvard
      School of Dental Medicine convened a leadership forum, "Put Your Money Where Your
      Mouth Is: The Economic Imperative of Oral Health." Based on the goals of that
      initiative to advocate for an integrated healthcare system, the authors have
      presented pertinent information from two major research projects and two major
      clinical programs, which, collectively, aim to bring oral health into primary
      care and raise the awareness of the connections between oral health and systemic
      health.

PMID- 27875053
TI  - Pharmacological Reversal Agents in Dental Practice: Keys to Patient Safety.
AB  - Though uncommon, medical emergencies in the dental office are harrowing
      occurrences that can be the result of adverse drug reactions. Pharmacological
      antagonists have been developed for administration as reversal agents in
      emergency situations in which patients may have an untoward effect, typically
      caused by too much medication. Dental practitioners should be familiar with these
      agents to keep patients safe and help mitigate drug-induced medical emergencies.
      This article reviews the pharmacokinetic and pharmacodynamic principles of
      pharmacological antagonists; it emphasizes six specific reversal agents as they
      relate to the clinical practice of dentistry: naloxone, flumazenil, epinephrine,
      diphenhydramine, phentolamine, and atropine. Outside of emergency situations, the
      pharmacological antagonist phentolamine has been developed to reverse the effects
      of the vasoconstrictor in dental local anesthesia preparations when the effects
      of the agonist medication are no longer required. Such newer reversal agents are
      being considered for more routine use once the dental procedure is complete. This
      article is intended to assist dental practitioners who are familiar with
      pharmacological antagonists to be better able to help mitigate drug-induced
      medical emergencies should they occur.

PMID- 27875054
TI  - The Role of Dietary Supplements in Postsurgical Bleeding: An Update for the
      Practitioner.
AB  - In the United States, dietary supplement use in adults aged 20 and older has
      increased significantly in the last 2 decades. Intraoperative and postoperative
      bleeding has been among the complications linked with usage, which is
      particularly problematic if patients do not disclose use to the dental
      practitioner. The aim of this article is to present a case report of a patient
      who had been taking dietary supplements for only 1 month and developed severe
      bleeding after receiving second-stage implant abutment insertion surgery. The
      article also presents a review of several supplements that can increase the risk
      for bleeding complications.

PMID- 27875055
TI  - Intraoral Repair of a Glass-Ceramic Restoration With Nanohybrid Ormocers: A Case
      Report.
AB  - The interest in repairing failed restorations has been growing; such a procedure
      may prolong the life span of defective direct and indirect dental restorations.
      The intraoral repair using resin-based composite materials has major benefits, as
      it preserves the main body of the restoration, avoids unnecessary removal of
      sound tooth structure, is an easy and fast treatment, avoids additional
      appointments, and is inexpensive. This case report demonstrates the use of
      nanohybrid Ormocer(r), or organically modified ceramic, materials.

PMID- 27875056
TI  - Opioid, NSAID, and OTC Analgesic Medications for Dental Procedures: PEARL Network
      Findings.
AB  - OBJECTIVE: Dental treatment is often categorized as a moderately or severely
      painful experience; however, no clinical data reported by the patient and dentist
      currently exists to support this degree of pain. This has contributed possibly to
      the overprescribing of analgesics, in particular the opioid class of medications.
      The primary objective of the study was to document the dentists' postprocedural
      prescriptions and recommendations for analgesic medications and their
      effectiveness for a 5-day period. Medications prescribed or recommended in the
      patient-reported outcomes included: opioid, nonsteroidal anti-inflammatory drugs
      (NSAIDs), and over-the-counter (OTC) analgesics. Met hods : This study used both
      dentist and patient responses to evaluate the use of opioid, NSAID, and OTC
      recommended or prescribed analgesics following one of seven classes of dental
      procedures encompassing over 22 specific coded procedures thought to elicit pain.
      The patient-centered study included a 5-day postprocedural patient follow-up
      assessment of the medication's effectiveness in relieving pain. RESULTS: Baseline
      questionnaires were completed by 2765 (99.9%) of 2767 eligible patients, and 2381
      (86%) patients responded to the Day 5 follow-up questionnaires. CONCLUSION: The
      data suggest NSAIDs, both OTC and prescribed dosages, may be a sufficient
      analgesic to treat most postoperative dental pain. Clinical judgment as to the
      use of an opioid should include the physiological principles related to the
      pharmacology of pain and inflammation and may include a central effect.
      ClinicalTrials.gov Identifier: NCT02929602.

PMID- 27875058
TI  - Antenatal Stressful Life Events and Postpartum Depressive Symptoms in the United
      States: The Role of Women's Socioeconomic Status Indices at the State Level.
AB  - BACKGROUND: Approximately 10%-20% of women suffer from postpartum depression
      (PPD), important predictors of which are antenatal stressful life event (SLE)
      experiences. The association between women's state-level socioeconomic status
      (SES) and PPD has not been explored. This study aimed to examine whether the
      association between antenatal SLE and PPD symptoms was moderated by women's state
      level SES. METHODS: Data from the 2009-2011 Pregnancy Risk Assessment Monitoring
      System (PRAMS) were used. State-level women's employment/earnings and
      social/economic autonomy indices were computed from indicators published by the
      Institute of Women's Policy Research (IWPR). Multilevel multivariable logistic
      regression analyses were performed. RESULTS: Among 91,253 women with valid
      responses, 11.3% had PPD symptoms, prevalence ranging from 7.1% in Illinois to
      17.1% in Arkansas. Women who experienced all four stressor categories, including
      partner related, traumatic, emotional, and financial, had the highest odds
      (adjusted odds ratio [aOR]: 5.43; 95% confidence interval [CI]: 5.36-5.51) of PPD
      symptoms. The odds of experiencing PPD symptoms decreased with an increase in the
      state-level social/economic autonomy index (aOR: 0.75; 95% CI: 0.64-0.88). There
      was significant cross-level interaction between number of stressor categories
      experienced and state-level index. CONCLUSIONS: Screening for antenatal SLEs can
      help identify women at risk for PPD symptoms. That the odds of having PPD
      symptoms decreased with increasing state-level social/economic autonomy and women
      residing in states with lower indices were more vulnerable to the impacts of
      antenatal stressors, could have policy implications related to improving the SES
      of women in these states.

PMID- 27875059
TI  - Cortical Bone Area Predicts Incident Fractures Independently of Areal Bone
      Mineral Density in Older Men.
AB  - Context: Areal bone mineral density (aBMD) measured using dual-energy X-ray
      absorptiometry (DXA) is used clinically to predict fracture but does not
      discriminate between trabecular and cortical bone assessment. Objective: This
      study aimed to investigate whether information on cortical and trabecular bone
      predict fracture risk independently of aBMD and clinical risk factors. Design and
      Participants: Cortical area, bone mass, porosity, and trabecular bone volume
      fraction (BVTV) were measured at the tibia using high-resolution peripheral
      quantitative computed tomography (HR-pQCT) in 456 men (80.2 +/- 3.5 years)
      recruited from the general population in Gothenburg, Sweden. aBMD was measured
      using DXA. Incident fractures (71 men) were X-ray verified. Associations were
      evaluated using Cox regression. Results: Cortical area [hazard ratio (HR) per
      standard deviation (SD) decrease, 2.05; 95% confidence interval (CI), 1.58 to
      2.65], cortical bone mass (HR, 2.07; 95% CI, 1.58 to 2.70), and BVTV (HR, 1.62;
      95% CI, 1.26 to 2.07), but not cortical porosity, were independently associated
      with fracture risk. These associations remained after adjustment for femoral neck
      aBMD and Fracture Risk Assessment risk factors (area: HR 1.96, 95% CI, 1.44 to
      2.66; mass: HR 1.99, 95% CI, 1.45 to 2.74; BV/TV: HR 1.46, 95% CI, 1.09 to 1.96).
      After entering BV/TV and cortical area or bone mass simultaneously in the
      adjusted models, only the cortical parameters remained important predictors of
      fracture. Conclusion: HR-pQCT measurement of cortical area and mass might add
      clinically useful information for the evaluation of fracture risk.

PMID- 27875060
TI  - Open versus Thoracoscopic RFA-Assisted Lung Resection.
AB  - The purpose of this study was to evaluate Radio Frequency Ablation (RFA)-assisted
      lung parenchymal transection through thoracotomy and thoracoscopy. Twelve
      domestic pigs underwent RFA-assisted lingulectomy: six through thoracotomy (group
      A), and six with thoracoscopy (group B). There was no mortality, no bleeding, or
      air leak intra- or postoperatively in either of the groups, and no conversion to
      open thoracotomy in group B. Group A had longer operating period and more pleural
      adhesions. A barotrauma, a skin burn, and a localized infection were observed in
      this group. Histopathology confirmed a sharply demarcated area of coagulation
      necrosis without damage to adjacent structures. RFA-assisted lung resection
      through thoracotomy bears the inherent problems of an open approach, and the use
      of RFA device does not add to morbidity. The thoracoscopic use of RFA probe by
      experienced surgeons is considered safe, maintaining the advantages of key-hole
      surgery.

PMID- 27875057
TI  - National Athletic Trainers' Association Position Statement: Preventing and
      Managing Sport-Related Dental and Oral Injuries.
AB  - OBJECTIVE: To provide athletic trainers, health care professionals, and all those
      responsible for the care of athletes with clinical recommendations for preventing
      and managing sport-related dental and oral injuries. BACKGROUND: Participation in
      competitive sports continues to grow at both the interscholastic and
      intercollegiate levels. Therefore, exposure to, and the incidence of athletic
      related injury, including orofacial injury, will also likely increase. At the
      time of this writing, the leading governing agencies for interscholastic
      (National Federation of State High School Associations) and intercollegiate
      (National Collegiate Athletic Association) sports require only protective
      orofacial equipment (eg, mouthguards) for 5 and 4, respectively, of their
      sanctioned sports. Although orofacial injuries represent a small percentage of
      all sport-related injuries, the financial burden associated with these injuries
      (eg, tooth avulsion) can exceed $15 000 over an adult life. Therefore, effective
      management of sport-related dental injuries is critical to the long-term
      financial, physical, and emotional health of people who have experienced dental
      trauma. RECOMMENDATIONS: Based upon the current evidence regarding sport-related
      orofacial injury, we provide recommendations related to planning considerations,
      education, and mouthguard efficacy, material, fabrication, and care
      considerations. Additionally, suggested best practices for managing sport-related
      dental injury are also given for athletic trainers and other health care
      professionals.

PMID- 27875061
TI  - Glycemic Control Reduces Infections in Post-Liver Transplant Patients: Results of
      a Prospective, Randomized Study.
AB  - Context: Previous studies have shown a relationship between glycemic control and
      posttransplant morbidity. Objective: We conducted a prospective randomized
      controlled trial in postliver transplant patients to evaluate intensive inpatient
      glycemic control and effects on outcomes to 1 year. Research Design and
      Intervention: A total of 164 patients [blood glucose (BG) >180 mg/dL] were
      randomized into 2 target groups: 82 with a BG of 140 mg/dL and 82 with a BG of
      180 mg/dL. Continuous insulin infusions were initiated and then converted to
      subcutaneous basal bolus insulin therapy by our glucose management service.
      Results: The inpatient mean BG level was significantly different (140 group,
      151.4 +/- 19.5 mg/dL vs 180 group, 172.6 +/- 27.9 mg/dL; P < 0.001). Any
      infection within 1 year occurred in 35 of the 82 patients (42.7%) in the 140
      group and 54 of 82 (65.9%) in the 180 group (P = 0.0046). In a time-to-first
      infection analysis, being in the 140 group resulted in a hazard ratio of 0.54
      (95% confidence interval, 0.35 to 0.83; P = 0.004); the difference between the 2
      groups was statistically significant at 1 month (P = 0.008). The number with
      adjudicated transplant rejection was similar between the 2 groups [17 of 82
      (20.7%) and 20 of 82 (24.3%) in the 140 and 180 groups, respectively; P = not
      significant]. Severe hypoglycemia (BG <=40 mg/dL) occurred in 3 patients (2 in
      the 140 group and 1 in the 180 group). However, more patients had moderate
      hypoglycemia (BG, 41 to 70 mg/dL) in the 140 group [27 of 82 (32.9%) vs 10 of 82
      (12.2%) in the 180 group; P = 0.003]. Insulin-related hypoglycemia was not
      associated with the incidence of severe adverse outcomes. Conclusions: Glycemic
      control of 140 mg/dL safely resulted in a reduced incidence of infection after
      transplantation compared with 180 mg/dL, but with an increase in moderate
      hypoglycemia.

PMID- 27875062
TI  - Role of risk stratification and genetics in sudden cardiac death.
AB  - Sudden cardiac death (SCD) is a major public health issue due to its increasing
      incidence in the general population and the difficulty in identifying high-risk
      individuals. Nearly 300 000 - 350 000 patients in the United States and 4-5
      million patients in the world die annually from SCD. Coronary artery disease and
      advanced heart failure are the main etiology for SCD. Ischemia of any cause
      precipitates lethal arrhythmias, and ventricular tachycardia and ventricular
      fibrillation are the most common lethal arrhythmias precipitating SCD. Pulseless
      electrical activity, bradyarrhythmia, and electromechanical dissociation also
      result in SCD. Most SCDs occur outside of the hospital setting, so it is
      difficult to estimate the public burden, which results in overestimating the
      incidence of SCD. The insufficiency and limited predictive value of various
      indicators and criteria for SCD result in the increasing incidence. As a result,
      there is a need to develop better risk stratification criteria and find
      modifiable variables to decrease the incidence. Primary and secondary prevention
      and treatment of SCD need further research. This critical review is focused on
      the etiology, risk factors, prognostic factors, and importance of risk
      stratification of SCD.

PMID- 27875064
TI  - Correction to: Hum Gene Ther 2016;27(1):19-31.

PMID- 27875063
TI  - The diagnosis you wish you had never operated on: Pyoderma gangrenosum
      misdiagnosed as necrotizing fasciitis-a case report.

PMID- 27875065
TI  - Evaluation of a new solid non-aqueous self-double-emulsifying drug-delivery
      system for topical application of quercetin.
AB  - This study aimed to the evaluation of a new solid non-aqueous self-double
      emulsifying drug-delivery system (SDEDDS) for topical application of quercetin.
      The new formulation was prepared through two-step emulsification process and
      could spontaneously form oil-in-oil-in-water (O/O/W) double emulsions after
      dilution with aqueous medium, with inner oil phase mainly containing the drug.
      Solid state characterisation was performed by DSC and X-ray powder diffraction.
      Furthermore, the optimised QT-SDEDDS displayed sustained release profile and was
      found to be stable up to 30 days under 4  degrees C and 25  degrees C.
      Antioxidant capacities showed that quercetin could be protected by the solid non
      aqueous SDEDDS. Compared with the quercetin ethanol aqueous solution, the QT
      SDEDDS exhibited higher permeation ability, and significantly increased
      accumulation of quercetin in the skin. These studies demonstrated that the solid
      non-aqueous SDEDDS might be a promising carrier for topical application of poorly
      water-soluble and simultaneously poorly oil-soluble drugs, such as quercetin.

PMID- 27875066
TI  - Sexuality and the Internet: A Study of the Perspectives of Turkish University
      Students.
AB  - The purpose of this study was to determine Turkish university students' uses of
      and attitudes toward the Internet concerning sexuality. The study was conducted
      in two public universities in the Central Anatolia and Eastern Anatolia regions
      of Turkey. Among the students invited to take part in the study, 1,330 students
      agreed to do so. The study data were collected using a questionnaire designed by
      researchers to determine participants' personal characteristics, computer and
      Internet uses in general, and for sexual matters. The findings suggest that
      approximately half of the students (51%) reported using the Internet to obtain
      information about sexuality. Among the students, 30.5% said that they visit
      erotic and pornographic Web sites, 21.1% said that they chat on the Internet
      about sexuality, and 9.3% said that they bought sexual products online. Compared
      to the female students, the male students, statistically, more frequently show
      behaviors such as obtaining sexual information on the Internet, online sexual
      shopping, chatting on the Internet about sexuality, and visiting pornographic and
      erotic Web sites. In addition, female students have more negative attitudes
      toward using the Internet for sexual purposes. This study discusses its results
      along with the literature from Turkey and other countries.

PMID- 27875069
TI  - Turning ASCO Members Into Conquer Cancer Foundation Donors.

PMID- 27875067
TI  - Transiently expressed ATG16L1 inhibits autophagosome biogenesis and aberrantly
      targets RAB11-positive recycling endosomes.
AB  - The membrane source for autophagosome biogenesis is an unsolved mystery in the
      study of autophagy. ATG16L1 forms a complex with ATG12-ATG5 (the ATG16L1
      complex). The ATG16L1 complex is recruited to autophagic membranes to convert
      MAP1LC3B-I to MAP1LC3B-II. The ATG16L1 complex dissociates from the phagophore
      before autophagosome membrane closure. Thus, ATG16L1 can be used as an early
      event marker for the study of autophagosome biogenesis. We found that among 3
      proteins in the ATG16L1 complex, only ATG16L1 formed puncta-like structures when
      transiently overexpressed. ATG16L1+ puncta formed by transient expression could
      represent autophagic membrane structures. We thoroughly characterized the
      transiently expressed ATG16L1 in several mammalian cell lines. We found that
      transient expression of ATG16L1 not only inhibited autophagosome biogenesis, but
      also aberrantly targeted RAB11-positive recycling endosomes, resulting in
      recycling endosome aggregates. We conclude that transient expression of ATG16L1
      is not a physiological model for the study of autophagy. Caution is warranted
      when reviewing findings derived from a transient expression model of ATG16L1.

PMID- 27875070
TI  - Competitive Funding Strategies for the Conquer Cancer Foundation of ASCO.
AB  - PURPOSE: The Conquer Cancer Foundation (CCF), the philanthropic arm of ASCO, is
      responsible for funding innovative clinical research. CCF wants to broaden its
      donor base instead of relying predominantly on health-care companies. Our
      Leadership Development Program (LDP) group was tasked with identifying potential
      donor sources and making recommendations to increase funding. MATERIALS AND
      METHODS: We selected three sources to research: the general public,
      crowdsourcing/social media, and ASCO members. We subsequently focused our efforts
      on ASCO members, of whom only 2% to 3% are donors to CCF and < 8% are repeat
      donors. To analyze this low rate, we sent out two separate surveys to various
      groups of members within ASCO. RESULTS: We identified lack of knowledge as a
      major deterrent to giving; surprisingly, even those who hold ASCO leadership
      positions or participated in committees lacked knowledge about CCF funding. Also,
      the misconception that ASCO is rich and does not need philanthropic support
      deterred giving; however, respondents would donate if given the right message
      that stresses the need of continued member-led donations. CONCLUSION: ASCO
      members, including those in leadership positions, need to be engaged more
      aggressively to support CCF. Increased education and updating the CCF message is
      likely to provide the greatest impact on higher member donation, repeated
      donations, and facilitate CCF's goal of diversifying its donor base away from
      healthcare companies. Furthermore, we recommend using technology, such as mobile
      applications, and providing incentives and visibility to major donors.

PMID- 27875071
TI  - In Response to "Cancer-Related Hypercalcemia".

PMID- 27875072
TI  - Reply to C. Taylor.

PMID- 27875073
TI  - Orthodox Jewish Thought Leaders' Insights Regarding BRCA Mutations: A Descriptive
      Study.
AB  - PURPOSE: To examine the factors that influence Orthodox Jewish (OJ) thought
      leaders' perceptions of genetic counseling and testing for BRCA mutations. The
      specific aims of this study were to describe (1) OJ thought leaders' views on
      genetic counseling and testing for BRCA mutation status and (2) insights into
      this high-risk faith-based minority group and their beliefs about counseling and
      testing for BRCA mutations. METHODS: In-depth focus groups and demographic
      questionnaires were used in this descriptive, qualitative study, which was
      performed in the cancer center of a 750-bed community teaching hospital in
      Brooklyn, New York. Participants included 17 OJ thought leaders in a large
      metropolitan area in the northeastern United States. RESULTS: Four themes emerged
      that describe the key components of the views of OJ thought leaders regarding
      genetic counseling and testing for BRCA mutation carriers. There was a high level
      of concern about cancer, recognition that community norms shift, acknowledgment
      of the role of the rabbi in medical decision making, and concern about the
      balance between determinism and personal responsibility in utilizing this health
      care service. CONCLUSION: The identification of social contributors to the
      utilization of genetic counseling and testing, as well as identification of
      solutions to optimize utilization of BRCA testing, supports the philosophic
      premise or conceptual model that faith-based leaders are crucial to the promotion
      of culturally sensitive health care delivery. Incorporating faith-based leaders
      early in health care strategic planning and implementation can translate into
      communities better utilizing health-related services.

PMID- 27875074
TI  - Right ventricular dysfunction after cardiac surgery - diagnostic options.
AB  - Right ventricular (RV) failure after cardiac surgery is associated with an
      ominous prognosis. The etiology of RV failure is multifaceted and the ability to
      recognize RV failure early is paramount in order to initiate timely treatment.
      The present review focuses on different diagnostic modalities for RV function and
      discusses the normal versus abnormal findings in RV monitoring after cardiac
      surgery and the limitations of the applicable diagnostic modalities. There are
      specific challenges in RV assessment after cardiac surgery due to a loss of
      longitudinal contraction and a concomitant gain of transverse contraction.
      Additionally, the image quality of transthoracic echocardiography (TTE) is often
      reduced after cardiac surgery. RV function can be assessed with 2D and 3D imaging
      techniques as well as invasive hemodynamic monitoring. Until proper validation
      studies have determined accuracy, reproducibility and comparability of the next
      generation of diagnostic modalities we propose to use simple, but obtainable
      echocardiographic measurements and ultimately the insertion of a pulmonary artery
      catheter (PAC) in order to diagnose RV failure after cardiac surgery.

PMID- 27875075
TI  - Chamomile and oregano extracts synergistically exhibit antihyperglycemic,
      antihyperlipidemic, and renal protective effects in alloxan-induced diabetic
      rats.
AB  - The bio-activities of separate Matricaria chamomilla (chamomile) and Origanum
      vulgare (oregano) are well studied; however, the combined effects of both natural
      products in animal diabetic models are not well characterized. In this study,
      alloxan-induced male albino rats were treated with single dose aqueous suspension
      of chamomile or oregano at dose level of either 150 or 300 mg/kg body mass or as
      equal parts as combination by stomach tube for 6 weeks. After treatment, blood
      samples were assessed for diabetic, renal, and lipid profiles. Insulin, amylase
      activity, and diabetic renal apoptosis were further evaluated. Treatment with
      higher dose of the extracts (300 mg/kg) as individual or as mixture of low doses
      (150 mg/kg of both the extracts) had significant mass gain, hypoglycemic effect
      (p <= 0.05) with decreased amylase activity and increased serum insulin levels.
      Restoration of renal profile, lipid profile with increase in HDL-c (p <= 0.05)
      along with reversal of pro-apoptotic Bax and anti-apoptotic Bcl-2 were well
      observed with 300 mg/kg mixture, showing synergistic activity of the extracts
      compared with individual low dose of 150 mg/kg. Collectively, our results
      indicate that combination of chamomile and oregano extracts will form a new class
      of drugs to treat diabetic complications.

PMID- 27875076
TI  - Correlates of Resource Empowerment among Parents of Children with Overweight or
      Obesity.
AB  - BACKGROUND: Few studies have examined correlates of resource empowerment among
      parents of children with overweight or obesity. METHODS: We studied baseline data
      of 721 parent-child pairs participating in the Connect for Health randomized
      trial being conducted at six pediatric practices in Massachusetts. Parents
      completed the child weight management subscale (n = 5 items; 4-point response
      scale) of the Parent Resource Empowerment Scale; items were averaged to create a
      summary empowerment score. We used linear regression to examine the independent
      effects of child (age, sex, and race/ethnicity), parent/household characteristics
      (age, education, annual household income, BMI category, perceived stress, and
      their ratings of their healthcare quality), and neighborhood median household
      income, on parental resource empowerment. RESULTS: Mean (SD) child age was 7.7
      years (2.9) and mean (SD) BMI z-score was 1.9 (0.5); 34% of children were white,
      32% black, 22% Hispanic, 5% Asian, and 6% multiracial/other. The mean parental
      empowerment score was 2.95 (SD = 0.56; range = 1-4). In adjusted models, parents
      of older children [beta -0.03 (95% CI: -0.04, -0.01)], Hispanic children [-0.14 (
      0.26, -0.03)], those with annual household income less than $20,000 [-0.16 (
      0.29, -0.02)], those with BMI >=30.0 kg/m2 [-0.17 (-0.28, -0.07)], and those who
      reported receiving lower quality of obesity-related care [-0.05 (-0.07, -0.03)]
      felt less empowered about resources to support their child's healthy body weight.
      CONCLUSIONS: Parental resource empowerment is influenced by parent and child
      characteristics as well as the quality of their obesity-related care. These
      findings could help inform equitable, family-centered approaches to improve
      parental resource empowerment.

PMID- 27875078
TI  - Pathology in Practice.

PMID- 27875080
TI  - In This Issue * December 1, 2016.

PMID- 27875077
TI  - MARCH5 RNA promotes autophagy, migration, and invasion of ovarian cancer cells.
AB  - MARCH5 is a crucial regulator of mitochondrial fission. However, the expression
      and function of MARCH5 in ovarian cancer have not been determined. This study
      investigated the expression and function of MARCH5 in ovarian cancer with respect
      to its potential role in the tumorigenesis of the disease as well as its
      usefulness as an early diagnostic marker. We found that the expression of MARCH5
      was substantially upregulated in ovarian cancer tissue in comparison with the
      normal control. Silencing MARCH5 in SKOV3 cells decreased TGFB1-induced cell
      macroautophagy/autophagy, migration, and invasion in vitro and in vivo, whereas
      the ectopic expression of MARCH5 in A2780 cells had the opposite effect.
      Mechanistic investigations revealed that MARCH5 RNA may function as a competing
      endogenous RNA (ceRNA) to regulate the expression of SMAD2 and ATG5 by competing
      for MIR30A. Knocking down SMAD2 or ATG5 can block the effect of MARCH5 in A2780
      cells. Also, silencing the expression of MARCH5 in SKOV3 cells can inhibit the
      TGFB1-SMAD2/3 pathway. In contrast, the ectopic expression of MARCH5 in A2780
      cells can activate the TGFB1-SMAD2/3 pathway. In turn, the TGFB1-SMAD2/3 pathway
      can regulate MARCH5 and ATG5 through MIR30A. Overall, the results of this study
      identified MARCH5 as a candidate oncogene in ovarian cancer and a potential
      target for ovarian cancer therapy.

PMID- 27875079
TI  - Comparison of body condition score and urinalysis variables between dogs with and
      without calcium oxalate uroliths.
AB  - OBJECTIVE To compare body condition score (BCS) and urinalysis variables between
      dogs with and without calcium oxalate (CaOx) uroliths. DESIGN Case-control study.
      ANIMALS 46 Miniature Schnauzers, 16 Bichons Frises, and 6 Shih Tzus. PROCEDURES
      Medical records were reviewed for Miniature Schnauzers, Bichons Frises, and Shih
      Tzus that were examined between January 2001 and November 2014 for another
      urolithiasis study or for a urolith removal procedure. Dogs with CaOx uroliths
      were classified as cases. Dogs without a history of urinary tract disease and
      with no evidence of radiopaque uroliths on abdominal radiographs were classified
      as controls. Each case was matched with 1 control on the basis of age (+/- 2
      years), sex, and breed. Body condition score and urinalysis results were compared
      between cases and controls, and the relationship between BCS and urine pH was
      analyzed. RESULTS Median BCS was significantly greater for cases than controls,
      although the proportion of overweight dogs did not differ significantly between
      the 2 groups. Urine pH was negatively associated with age, but was not associated
      with BCS or the presence of CaOx uroliths. Cases infrequently had acidic urine or
      CaOx crystalluria but frequently had hematuria and proteinuria. CONCLUSIONS AND
      CLINICAL RELEVANCE Results indicated that dogs with CaOx uroliths had a greater
      median BCS than control dogs, but the clinical importance of that finding was
      unclear. Acidic urine and CaOx crystalluria were uncommon and not adequate
      predictors of CaOx urolith status. Hematuria and proteinuria were commonly
      observed in dogs with CaOx urolithiasis, but they are not pathognomonic for that
      condition.

PMID- 27875081
TI  - What Is Your Neurologic Diagnosis?

PMID- 27875082
TI  - Effects of trazodone on behavioral signs of stress in hospitalized dogs.
AB  - OBJECTIVE To determine the effects of trazodone treatment on behavioral signs of
      stress in hospitalized dogs. DESIGN Prospective observational study. ANIMALS 120
      client-owned dogs. PROCEDURES Hospitalized dogs administered trazodone (n = 60)
      were observed for stress-related signs or behaviors <= 45 minutes after the drug
      was administered (time 1) and approximately 90 minutes later (time 2). Dogs that
      did not receive trazodone (n = 60) were selected to serve as controls for
      environmental stimuli that could affect behavior and were observed at the same
      times. Signs or behaviors (scored as present or absent) were assessed
      individually and grouped into behavioral summation categories (frenetic [lip
      licking, pacing, panting, spinning, trembling, wet dog shake, whining, and
      yawning], freeze [averting gaze, pinning back ears, and whale eye sign], or
      fractious [growling, lunging, showing teeth, and snapping], with lifting of a
      forelimb and pupil dilation included in all categories). Results were compared
      between groups and within groups over time. Logistic regression was performed to
      assess associations between reduction in stress-related signs or behaviors and
      trazodone administration while controlling for environmental influences. RESULTS
      Lip licking, panting, and whining were reduced (defined as present at time 1 and
      absent at time 2) in trazodone-treated but not environmentally matched dogs. The
      median number of stress-related behaviors and of frenetic and freeze behaviors
      was significantly lower at time 2, compared with time 1, in trazodone-treated
      dogs. Odds of reduced panting and reduced frenetic behaviors at time 2 for
      trazodone-treated dogs were > 2 times those for environmentally matched dogs.
      CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that trazodone
      administration reduced stress-related signs and behaviors in hospitalized dogs
      and may thereby improve patient welfare.

PMID- 27875083
TI  - Outcome in cats with benign ureteral obstructions treated by means of ureteral
      stenting versus ureterotomy.
AB  - OBJECTIVE To evaluate the outcome for cats with benign ureteral obstructions
      treated by means of ureteral stenting and to compare the outcome for these cats
      with outcome for a historical cohort of cats treated by means of ureterotomy
      only. DESIGN Prospective study with historical cohort. ANIMALS 62 client-owned
      cats with benign ureteral obstructions, including 26 cats treated with ureteral
      stenting and 36 cats previously treated with ureterotomy. PROCEDURES Data were
      recorded prospectively (ureteral stent cases) or collected retrospectively from
      the medical records (ureterotomy cases), and results were compared. RESULTS Cats
      treated with ureteral stents had significantly greater decreases in BUN and serum
      creatinine concentrations 1 day after surgery and at hospital discharge, compared
      with values for cats that underwent ureterotomy. Six cats in the ureteral stent
      group developed abdominal effusion after surgery, and cats in this group were
      significantly more likely to develop abdominal effusion when a ureterotomy was
      performed than when it was not. Cats that developed abdominal effusion after
      surgery were significantly less likely to survive to hospital discharge. Cats
      that underwent ureteral stenting were significantly more likely to have
      resolution of azotemia prior to hospital discharge than were cats that underwent
      ureterotomy alone. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that cats
      with benign ureteral obstructions treated with ureteral stenting were more likely
      to have resolution of azotemia prior to hospital discharge, compared with cats
      undergoing ureterotomy alone. Results of ureteral stenting were encouraging, but
      further investigation is warranted.

PMID- 27875084
TI  - What Is Your Diagnosis?

PMID- 27875085
TI  - Concurrent or sequential tibial subchondral cystic lesions in 4 horses with
      medial femoral condyle subchondral cystic lesions.
AB  - CASE DESCRIPTION 4 horses were examined because of signs of chronic hind limb
      lameness. CLINICAL FINDINGS 3 horses had a history of lameness for > 6 months;
      specific duration was unknown for 1 horse. On initial evaluation, grade 3 to 4
      (on a scale from 1 to 5) hind limb lameness was present in all 4 horses.
      Radiography of the stifle joint of the affected limb revealed medial femoral
      condyle subchondral lucencies or subchondral cystic lesions (SCLs) in all 4
      horses, medial femorotibial osteoarthritis in 3 horses, and medial tibial condyle
      SCLs in 3 horses. TREATMENT AND OUTCOME 2 horses were treated medically (stall
      rest and oral NSAID administration), and 2 horses were treated surgically by
      means of medial femoral transcondylar lag screw placement through the medial
      femoral condyle SCLs. The 2 horses treated medically did not improve and were
      euthanized. Necropsy confirmed the presence of medial femoral condyle and medial
      tibial condyle SCLs. Surgical treatment did not resolve the lameness in 1 horse
      with SCLs in the medial tibial condyle and medial femoral condyle, and euthanasia
      was performed 150 days after surgery. In the second horse, a medial tibial
      condyle SCL was evident on radiographs obtained 3 months after surgery; however,
      this was not addressed surgically, and signs of lameness resolved 11 months after
      surgery. CLINICAL RELEVANCE Results of this small case series suggested that SCLs
      in the medial tibial condyle can occur in association with SCLs of the medial
      femoral condyle, with a poor prognosis for return to athletic function in
      affected horses. Further investigation is indicated.

PMID- 27875087
TI  - Pathology in Practice.

PMID- 27875088
TI  - Letters to the Editor.

PMID- 27875089
TI  - The essential nature of dietary omega-3 fatty acids in dogs.

PMID- 27875090
TI  - Clinical, computed tomographic, magnetic resonance imaging, and histologic
      findings associated with myxomatous neoplasia of the temporomandibular joint in
      two dogs.
AB  - CASE DESCRIPTION A 15-year-old neutered female mixed-breed dog (dog 1) and an 11
      year-old neutered female Labrador Retriever (dog 2) were examined because of
      unilateral exophthalmus, third eyelid protrusion, and periorbital swelling that
      failed to respond to antimicrobial treatment. CLINICAL FINDINGS Both dogs
      underwent ultrasonographic, CT, and MRI examination of the head. In both dogs,
      advanced imaging revealed a poorly defined, peripherally contrast-enhancing,
      mucous-filled cystic mass that radiated from the temporomandibular joint and
      infiltrated the periorbital tissues and retrobulbar space. Both dogs underwent
      surgical biopsy of the periorbital mass. A viscous, straw-colored fluid was
      aspirated from the retrobulbar region in both dogs. The initial histologic
      diagnosis for dog 1 was zygomatic sialadenitis and sialocele. However, the
      clinical signs recurred, and histologic examination of specimens obtained during
      a second surgical biopsy resulted in a diagnosis of myxoma. The histologic
      diagnosis was myxosarcoma for dog 2. TREATMENT AND OUTCOME In both dogs, clinical
      signs recurred within 2 weeks after surgery and persisted for the duration of
      their lives. Dog 1 received no further treatment after the second surgery and was
      euthanized 34 months after initial examination because of multicentric lymphoma.
      Dog 2 was treated with various chemotherapy agents and was euthanized 11 months
      after initial examination because of a dramatic increase in periocular swelling
      and respiratory stertor. CLINICAL RELEVANCE Temporomandibular myxomatous
      neoplasia can be confused with zygomatic sialocele on the basis of clinical signs
      but has characteristic MRI features. Representative biopsy specimens should be
      obtained from areas close to the temporomandibular joint to avoid misdiagnosis.

PMID- 27875091
TI  - What is the level of passion for our professionalism?

PMID- 27875092
TI  - Morphological variability of Demodex cati in a feline immunodeficiency virus
      positive cat.
AB  - CASE DESCRIPTION A 17-year-old FIV-positive cat was evaluated because of weight
      loss during the preceding few months. The cat had a weight loss of 0.5 kg (1.1
      lb) during the last month. Because of its FIV-positive status, the cat was
      confined indoors. CLINICAL FINDINGS A large nonpruritic area of alopecia with
      hyperpigmentation and comedones was present on the right lateral aspect of the
      neck. The chin had diffuse alopecia and comedones. Mild alopecia was present on
      the dorsal aspect of the muzzle. Trichography and microscopic examination of
      acetate tape imprint preparations and skin scrapings revealed a very
      morphologically heterogeneous population of Demodex mites. Micrometry of adult
      mites revealed a broad range of body lengths (92.68 to 245.94 MUm), which
      suggested that as many as 3 Demodex spp might be present in the skin lesions of
      this cat. TREATMENT AND OUTCOME Owing to its concurrent disease, no treatment was
      initiated for the demodicosis, and the cat died spontaneously 14 days after the
      evaluation. Sequence analysis of the 16S rRNA gene of collected mites was
      performed. Analysis revealed that the 16S rRNA gene sequence of collected mites
      appeared 100% identical to the Demodex cati 16S rRNA gene sequence deposited in
      GenBank (JX193759). A similarity of 79.2% and 74.4% was found when the 16S rRNA
      gene sequence of collected mites was compared with that of Demodex gatoi
      (JX981921) and Demodex felis (KF052995), respectively. CLINICAL RELEVANCE
      Demodicosis in cats is often associated with underlying disease. In cats, FIV
      infection may lead to an altered immune response and induce species polymorphism
      of Demodex mites.

PMID- 27875094
TI  - Laparoscopic Radical Gastrectomy for Resectable Advanced Gastric Cancer Within
      Enhanced Recovery Programs: A Prospective Randomized Controlled Trial.
AB  - BACKGROUND: Enhanced recovery programs have become an important focus of
      perioperative management. A few studies have demonstrated the efficacy of an
      enhanced recovery after surgery (ERAS, which includes optimized pain control,
      restricted I.V. fluids, early initiation of postoperative oral feeding, and
      enforced mobilization) protocol in patients undergoing radical gastrectomy. We
      investigated the feasibility and safety of laparoscopic radical gastrectomy
      within ERAS programs. METHODS: In this single-center prospective randomized
      controlled trial conducted between September 2013 and August 2014, 149
      consecutive locally advanced gastric cancer patients (T2-4, any N, M0) diagnosed
      by the CT scanning were allocated to either ERAS group (N = 73) or conventional
      pathway group (N = 76). The same surgical technique was used in both groups, that
      is, laparoscopic gastrectomy with D2 lymphadenectomy and R0 resection. Intergroup
      differences were evaluated for clinical parameters and C-reactive protein for
      testing tissue injury. RESULTS: ERAS combined with laparoscopic gastrectomy was
      observed in our study. Recovery parameters such as time to return to normal diet
      (days) 1.90 +/- 0.71 versus 3.52 +/- 0.81, P = .003 and time to the first
      defecation (days) 2.97 +/- 1.23 versus 5.20 +/- 1.81, P = .015 were measured. The
      post hospital stay (days) in ERAS and the conventional care group were 6.38 +/-
      2.04 and 8.62 +/- 2.87, P < .001, respectively. No statistically significant
      intergroup differences were observed in terms of postoperative complications and
      C-reactive protein levels. One patient in the ERAS group was readmitted because
      of anastomotic leakage. No instances of deaths were reported during the 30-day
      follow-up period. CONCLUSION: This study demonstrates the feasibility and safety
      of ERAS protocol in advanced gastric cancer patients undergoing laparoscopic
      radical gastrectomy and was associated with shorter duration of hospital stay. (
      Clinicaltrials.gov Identifier No NCT02348229).

PMID- 27875093
TI  - Autolysosome biogenesis and developmental senescence are regulated by both Spns1
      and v-ATPase.
AB  - Spns1 (Spinster homolog 1 [Drosophila]) in vertebrates, as well as Spin
      (Spinster) in Drosophila, is a hypothetical lysosomal H+-carbohydrate
      transporter, which functions at a late stage of macroautophagy (hereafter
      autophagy). The Spin/Spns1 defect induces aberrant autolysosome formation that
      leads to developmental senescence in the embryonic stage and premature aging
      symptoms in adulthood. However, the molecular mechanism by which loss of
      Spin/Spns1 leads to the specific pathogenesis remains to be elucidated. Using
      chemical, genetic and CRISPR/Cas9-mediated genome-editing approaches in
      zebrafish, we investigated and determined a mechanism that suppresses embryonic
      senescence as well as autolysosomal impairment mediated by Spns1 deficiency.
      Unexpectedly, we found that a concurrent disruption of the vacuolar-type H+
      ATPase (v-ATPase) subunit gene, atp6v0ca (ATPase, H+ transporting, lysosomal, V0
      subunit ca) led to suppression of the senescence induced by the Spns1 defect,
      whereas the sole loss of Atp6v0ca led to senescent embryos similar to the single
      spns1 mutation. Moreover, we discovered that the combined stable defect seen in
      the presence of both the spns1 and atp6v0ca mutant genes still subsequently
      induced premature autophagosome-lysosome fusion marked by insufficient acidity,
      while extending developmental life span, compared with the solely mutated spns1
      defect. Our data suggest that Spns1 and the v-ATPase orchestrate proper
      autolysosomal biogenesis with optimal acidification that is critically linked to
      developmental senescence and survival.

PMID- 27875095
TI  - Routine Bronchoscopy and Fogarty Catheter Occlusion of Tracheoesophageal
      Fistulas.
AB  - INTRODUCTION: Use of a Fogarty catheter for emergent occlusion of
      tracheoesophageal fistulas (TEFs) has been described for use in unstable
      neonates. Our purpose was to describe a case series of elective Fogarty catheter
      occlusion of the TEF. MATERIALS AND METHODS: A formal operative laryngoscopy and
      rigid bronchoscopy were performed with Fogarty catheter placement into the
      fistula before surgical intervention. The balloon was inflated and gentle
      traction provided occlusion of the tract. An endotracheal tube was then placed in
      a midtracheal location irrespective of fistulous tract location. The Fogarty
      catheter was removed at the time of fistula ligation. RESULTS: Six patients
      underwent Fogarty catheter occlusion of the TEF at the time of repair. The
      average gestational age was 38 +/- 2 weeks and birth weight was 2499 +/- 399 g.
      Associated anomalies or comorbidities were present in 2 of 6 patients (33%). Five
      patients (83%) had an esophageal atresia with distal TEF, all of whom underwent
      surgical intervention before day of life (DOL) 2. Of these patients, 3 were
      performed thoracoscopically, 1 was converted from thoracoscopic to open, and 1
      was initiated as an open procedure. One patient had an H-type fistula, which was
      repaired through a cervical approach on DOL 48. Average time required for both
      bronchoscopy and Fogarty placement was 10 +/- 2 minutes. There were no
      complications associated with Fogarty catheter placement and catheter
      dislodgement did not occur during any of the procedures. CONCLUSION: Elective
      Fogarty catheter occlusion of TEF can be performed safely and expeditiously,
      alleviating many perioperative challenges of TEF.

PMID- 27875096
TI  - Paraesophageal Hernia Repair: Techniques for Success.
AB  - With the introduction of laparoscopy, the outcomes of patients undergoing
      paraesophageal hernia repair have improved dramatically. When the fundamentals of
      a proper repair are followed, patients can expect to have improvement in
      gastroesophageal reflux symptoms, including heartburn, regurgitation, chest pain,
      dysphagia, and dyspnea. Adhering to these principles will alleviate patients'
      symptoms and avoid reoperation. This article describes the approach to
      paraesophageal hernia repair, including patient evaluation, operative technique,
      and postoperative management. Esophageal lengthening and crural reinforcement
      with mesh are addressed as well. Adhering to the basic techniques outlined in
      this article should lead to successful and durable patient outcomes following a
      paraesophageal hernia repair.

PMID- 27875097
TI  - Role of exosomes in the protection of cellular homeostasis.
AB  - Due to their ability to shuttle proteins, lipids and genetic material between
      distant cells, exosomes promote extensive phenotypic changes in recipient cells,
      modulating immune responses, cellular migration, cancer metastasis or the
      spreading of neurotoxic protein aggregates in neurodegenerative diseases. Besides
      intercellular communication, exosome biogenesis and secretion permit the rapid
      release of a selective repertoire of compounds, conferring cells with an
      additional mechanism to fight alterations in protein, lipid or RNA homeostasis
      during stress or pathological conditions. Here, we review the dual role of the
      different quality control mechanisms arising from the endolysosomal system and
      the diverse situations that control the decision between degradation or
      secretion. The crosstalk between exosome secretion and the different cellular
      degradation mechanisms confers an additional layer of protection to maintain
      cellular integrity and homeostasis in a number of physiological and pathological
      conditions.

PMID- 27875098
TI  - HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for
      epithelium intrinsic cellular defense against bacterial pore-forming toxin in C.
      elegans.
AB  - Autophagy is an evolutionarily conserved intracellular system that maintains
      cellular homeostasis by degrading and recycling damaged cellular components. The
      transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate
      tolerance to bacterial infection, but less is known about the bona fide bacterial
      effector that activates HLH-30 and autophagy. Here, we reveal that bacterial
      membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner
      in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of
      animals to PFT toxicity through xenophagic degradation of PFT and repair of
      membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C.
      elegans. These results demonstrate that autophagic pathways and autophagy are
      induced partly at the transcriptional level through HLH-30 activation and are
      required to protect metazoan upon PFT intoxication. Together, our data show a new
      and powerful connection between HLH-30-mediated autophagy and epithelium
      intrinsic cellular defense against the single most common mode of bacterial
      attack in vivo.

PMID- 27875100
TI  - The Small GTPase Ral orchestrates MVB biogenesis and exosome secretion.
AB  - Extracellular vesicles are novel mediators of cell-cell communication. They are
      present in all species and involved in physiological and pathological processes.
      One class of extracellular vesicles, the exosomes, originate from an endosomal
      compartment, the MultiVesicular Body (MVB), and are released from the cell upon
      fusion of the MVB with the plasma membrane. Although different molecular
      mechanisms have been associated with MVB biogenesis and exosome secretion, how
      they coordinate remains poorly documented. We recently found that the small
      GTPase Ral contributes to exosome release in nematodes and mammalian tumor cells.
      More specifically, we found that C. elegans RAL-1 is required for the biogenesis
      of MVBs, and later for MVB fusion with the plasma membrane. Here, we discuss our
      results in relationship with other factors involved in extracellular vesicle
      production such as the ESCRT complex and Phospholipase 1D. We propose models to
      explain Ral function in exosome secretion, its conservation in animals, and its
      possible role in tumor progression.

PMID- 27875101
TI  - Nonwoven textile for use in a nanoparticle respiratory deposition sampler.
AB  - The nanoparticle respiratory deposition (NRD) sampler is a personal sampler that
      combines a cyclone, impactor, and a nylon mesh diffusion stage to measure a
      worker's exposure to nanoparticles. The concentration of titanium in the nylon
      mesh of the diffusion stage complicates the application of the NRD sampler for
      assessing exposures to titanium dioxide nanoparticles. This study evaluated
      commercially available nonwoven textiles for use as an alternative media in the
      diffusion stage of the NRD sampler. Three textiles were selected as containing
      little titanium from an initial screening of 11 textiles by field portable x-ray
      fluorescence (FPXRF). Further evaluation on these three textiles was conducted to
      determine the concentration of titanium and other metals by inductively coupled
      plasma-optical emission spectroscopy (ICP-OES), the number of layers required to
      achieve desired collection characteristics for use as the diffusion stage in the
      NRD sampler (i.e., the nanoparticulate matter, NPM, criterion), and the pressure
      drop associated with that number of layers.  Only three (two composed of cotton
      fibers, C1 and C2; and one of viscose bamboo and cotton fibers, BC) of 11
      textiles screened had titanium concentrations below the limit of detection the
      XRF device (0.15 ug/cm2). Multiple metals, including small amounts of titanium,
      were found in each of the three nonwoven textiles using ICP-OES. The number of 25
      mm-diameter layers required to achieve the collection efficiency by size required
      for the NRD sampler was three for C1 (R2 = 0.95 with reference to the NPM
      criterion), two for C2 (R2 = 0.79), and three for BC (R2 = 0.87). All measured
      pressure drops were less than theoretical and even the greatest pressure drop of
      65.4 Pa indicated that a typical personal sampling pump could accommodate any of
      the three nonwoven textiles in the NRD sampler. The titanium concentration,
      collection efficiency, and measured pressure drops show there is a potential for
      nonwoven textiles to be used as the diffusion stage of the NRD sampler.

PMID- 27875102
TI  - Obesity Increases Operative Time in Children Undergoing Laparoscopic
      Cholecystectomy.
AB  - INTRODUCTION: Few studies have assessed the impact of obesity on laparoscopic
      cholecystectomy (LC) in pediatric patients. MATERIALS AND METHODS: Children who
      underwent LC were identified from the 2012 to 2013 American College of Surgeons'
      National Surgical Quality Improvement Program Pediatrics data. Patient
      characteristics, operative details, and outcomes were compared. Multivariable
      logistic regression was utilized to identify predictors of increased operative
      time (OT) and duration of anesthesia (DOAn). RESULTS: In total, 1757 patients
      were identified. Due to low rates of obesity in children <9 years old, analyses
      were limited to those 9-17 (n = 1611, 43% obese). Among obese children, 80.6%
      were girls. A higher proportion of obese patients had diabetes (3.0% versus 1.0%,
      P < .01) and contaminated or dirty/infected wounds (15.1% versus 9.4%, P < .01).
      Complication rates were low. The most frequent indications for surgery were
      cholelithiasis/biliary colic (34.3%), chronic cholecystitis (26.9%), and biliary
      dyskinesia (18.2%). On multivariable analysis, obesity was an independent
      predictor of OT >90 (odds ratio [OR] 2.02; 95% confidence interval [95% CI] 1.55
      2.63), and DOAn >140 minutes (OR 1.86; 95% CI 1.42-2.43). CONCLUSIONS: Obesity is
      an independent risk factor for increased OT in children undergoing LC. Pediatric
      surgeons and anesthesiologists should be prepared for the technical and
      physiological challenges that obesity may pose in this patient population.

PMID- 27875099
TI  - The RhoB small GTPase in physiology and disease.
AB  - RhoB is a Rho family GTPase that is highly similar to RhoA and RhoC, yet has
      distinct functions in cells. Its unique C-terminal region is subject to specific
      post-translational modifications that confer different localization and functions
      to RhoB. Apart from the common role with RhoA and RhoC in actin organization and
      cell migration, RhoB is also implicated in a variety of other cellular processes
      including membrane trafficking, cell proliferation, DNA-repair and apoptosis.
      RhoB is not an essential gene in mice, but it is implicated in several
      physiological and pathological processes. Its multiple roles will be discussed in
      this review.

PMID- 27875103
TI  - Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone
      Metastases in Prostate Cancer: A Pilot Study.
AB  - Purpose To determine the usefulness of whole-body diffusion-weighted imaging
      (DWI) to assess the response of bone metastases to treatment in patients with
      metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A
      phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose)
      polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance
      (MR) imaging substudy; the study was approved by the institutional research
      board, and written informed consent was obtained. Whole-body DWI was performed at
      baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging.
      Areas of abnormal signal intensity on DWI images in keeping with bone metastases
      were delineated to derive total diffusion volume (tDV); five target lesions were
      also evaluated. Associations of changes in volume of bone metastases and median
      apparent diffusion coefficient (ADC) with response to treatment were assessed by
      using the Mann-Whitney test and logistic regression; correlation with prostate
      specific antigen level and circulating tumor cell count were assessed by using
      Spearman correlation (r). Results Twenty-one patients were included. All six
      responders to olaparib showed a decrease in tDV, while no decrease was observed
      in all nonresponders; this difference between responders and nonresponders was
      significant (P = .001). Increases in median ADC were associated with increased
      odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P =
      .04). A positive association was detected between changes in tDV and best
      percentage change in prostate-specific antigen level and circulating tumor cell
      count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90],
      respectively). When assessing five target lesions, decreases in volume were
      associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80,
      0.99; P = .037). Conclusion This pilot study showed that decreases in volume and
      increases in median ADC of bone metastases assessed with whole-body DWI can
      potentially be used as indicators of response to olaparib in mCRPC. Online
      supplemental material is available for this article.

PMID- 27875104
TI  - CT-guided Native Medical Renal Biopsy: Cortical Tangential versus Non-Tangential
      Approaches-A Comparison of Efficacy and Safety.
AB  - Purpose To review a single-center experience with the cortical tangential
      approach during computed tomography (CT)-guided native medical renal biopsy and
      to evaluate its efficacy and safety compared with those of a non-cortical
      tangential approach. Materials and Methods This retrospective study received
      institutional review board approval, with a waiver of the HIPAA requirement for
      informed consent. The number of cores, glomeruli, and complications were reviewed
      in 431 CT-guided medical renal biopsies performed between July 2007 and September
      2015. A biopsy followed a cortical tangential approach if the needle path was
      parallel to the renal cortical surface, at a depth closer to the renal capsule
      than the renal pelvic fat. A sample was considered adequate if the biopsy yielded
      at least 10 glomeruli at light microscopy, one glomerulus at immunofluorescence
      microscopy, and one glomerulus at electron microscopy. The chi2 test, the t test,
      the Mann-Whitney test, and logistic regression modeling of sample adequacy were
      performed. Results One hundred fifty-six (36%) of 431 biopsies were performed
      with the cortical tangential approach. More cores were obtained for the cortical
      tangential group (2.6 vs 2.4, P = .001); biopsy needle gauge was not
      significantly different (P = .076). More adequate samples were obtained in the
      cortical tangential group (66.7% vs 49.8%, P = .001), with more glomeruli (23 vs
      16, P = .014). Results were significant after controlling for needle gauge and
      number of cores (P = .008). The cortical tangential group had fewer complications
      (1.9% vs 7.3%, P = .018). Conclusion The cortical tangential approach, when
      applied to CT-guided native medical renal biopsies, results in higher rates of
      sample adequacy and lower rates of postprocedural complications. (c) RSNA, 2016.

PMID- 27875105
TI  - Renal Cell Carcinoma: Comparison of RENAL Nephrometry and PADUA Scores with
      Maximum Tumor Diameter for Prediction of Local Recurrence after Thermal Ablation.
AB  - Purpose To evaluate the performance of the radius, exophytic or endophytic,
      nearness to collecting system or sinus, anterior or posterior, and location
      relative to polar lines (RENAL) nephrometry and preoperative aspects and
      dimensions used for anatomic classification (PADUA) scoring systems and other
      tumor biometrics for prediction of local tumor recurrence in patients with renal
      cell carcinoma after thermal ablation. Materials and Methods This HIPAA-compliant
      study was performed with a waiver of informed consent after institutional review
      board approval was obtained. A retrospective evaluation of 207 consecutive
      patients (131 men, 76 women; mean age, 71.9 years +/- 10.9) with 217 biopsy
      proven renal cell carcinoma tumors treated with thermal ablation was conducted.
      Serial postablation computed tomography (CT) or magnetic resonance (MR) imaging
      was used to evaluate for local tumor recurrence. For each tumor, RENAL
      nephrometry and PADUA scores were calculated by using imaging-derived tumor
      morphologic data. Several additional tumor biometrics and combinations thereof
      were also measured, including maximum tumor diameter. The Harrell C index and
      hazard regression techniques were used to quantify associations with local tumor
      recurrence. Results The RENAL (hazard ratio, 1.43; P = .003) and PADUA (hazard
      ratio, 1.80; P < .0001) scores were found to be significantly associated with
      recurrence when regression techniques were used but demonstrated only poor to
      fair discrimination according to Harrell C index results (C, 0.68 and 0.75,
      respectively). Maximum tumor diameter showed the highest discriminatory strength
      of any individual variable evaluated (C, 0.81) and was also significantly
      predictive when regression techniques were used (hazard ratio, 2.98; P < .0001).
      For every 1-cm increase in diameter, the estimated rate of recurrence risk
      increased by 198%. Conclusion Maximum tumor diameter demonstrates superior
      performance relative to existing tumor scoring systems and other evaluated
      biometrics for prediction of local tumor recurrence after renal cell carcinoma
      ablation. (c) RSNA, 2016.

PMID- 27875106
TI  - Neoadjuvant Systemic Therapy in Breast Cancer: Association of Contrast-enhanced
      MR Imaging Findings, Diffusion-weighted Imaging Findings, and Tumor Subtype with
      Tumor Response.
AB  - Purpose To investigate the performance of tumor subtype and various magnetic
      resonance (MR) imaging parameters in the assessment of tumor response to
      neoadjuvant systemic therapy (NST) in patients with breast cancer and to outline
      a model of pathologic response, considering pathologic complete response (pCR) as
      the complete absence of any residual invasive cancer or ductal carcinoma in situ
      (DCIS). Materials and Methods This was an institutional review board-approved
      retrospective study, with waiver of the need to obtain informed consent. From
      November 2009 to December 2014, 111 patients with histopathologically confirmed
      invasive breast cancer who were undergoing NST were included (mean age, 54 years;
      range, 27-84 years). Breast MR imaging was performed before and after treatment.
      Presence of late enhancement was assessed. Apparent diffusion coefficients (ADCs)
      were obtained by using two different methods. ADC ratio (mean posttreatment
      ADC/mean pretreatment ADC) was calculated. pCR was defined as absence of any
      residual invasive cancer or DCIS. Multivariate regression analysis and receiver
      operating characteristic analysis were performed. Results According to their
      immunohistochemical (IHC) profile, tumors were classified as human epidermal
      growth factor receptor 2 (HER2) positive (n = 51), estrogen receptor (ER)
      positive/HER2 negative (n = 40), and triple negative (n = 20). pCR was achieved
      in 19% (21 of 111) of cases; 86% of them were triple-negative or HER2-positive
      subtypes. Absence of late enhancement at posttreatment MR imaging was
      significantly associated with pCR (area under the curve [AUC], 0.85). Mean ADC
      ratio significantly increased when pCR was achieved (P < .001). A kappa value of
      0.479 was found for late enhancement (P < .001), and the intraclass correlation
      coefficient for ADCs was 0.788 (P < .001). Good correlation of ADCs obtained with
      the single-value method and those obtained with the mean-value methods was
      observed. The model combining the IHC subtype, ADC ratio, and late enhancement
      had the highest association with pathologic response, achieving an AUC of 0.92
      (95% confidence interval: 0.86, 0.97). Conclusion Triple-negative or HER2
      positive tumors showing absence of late enhancement and high ADC ratio after NST
      are associated with pCR. (c) RSNA, 2016 Online supplemental material is available
      for this article.

PMID- 27875107
TI  - The Effect of Elevated Intra-Abdominal Pressure on TLR4 Signaling in Intestinal
      Mucosa and on Intestinal Bacterial Translocation in a Rat.
AB  - BACKGROUND: Recent evidence suggests that elevated intra-abdominal pressure (IAP)
      may adversely affect the intestinal barrier function. Toll-like receptor 4 (TLR
      4) is responsible for the recognition of bacterial endotoxin or
      lipopolysaccharide and for initiation of the Gram-negative septic shock syndrome.
      The objective of the current study was to determine the effects of elevated IAP
      on intestinal bacterial translocation (BT) and TLR-4 signaling in intestinal
      mucosa in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned
      to one of two experimental groups: sham animals (Sham) and IAP animals who were
      subjected to a 15 mmHg pressure pneumoperitoneum for 30 minutes. Rats were
      sacrificed 24 hours later. BT to mesenteric lymph nodes, liver, portal vein
      blood, and peripheral blood was determined at sacrifice. TLR4-related gene and
      protein expression (TLR-4; myeloid differentiation factor 88 [Myd88] and TNF
      alpha receptor-associated factor 6 [TRAF6]) expression were determined using real
      time PCR, western blotting, and immunohistochemistry. RESULTS: Thirty percent of
      sham rats developed BT in the mesenteric lymph nodes (level I) and 20% of control
      rats developed BT in the liver and portal vein (level II). abdominal compartment
      syndrome (ACS) rats demonstrated an 80% BT in the lymph nodes (Level I) and 40%
      BT in the liver and portal vein (Level II). Elevated BT was accompanied by a
      significant increase in TLR-4 immunostaining in jejunum (51%) and ileum (35.9%),
      and in a number of TRAF6-positive cells in jejunum (2.1%) and ileum (24.01%)
      compared to control animals. ACS rats demonstrated a significant increase in TLR4
      and MYD88 protein levels compared to control animals. CONCLUSIONS: Twenty-four
      hours after the induction of elevated IAP in a rat model, increased BT rates were
      associated with increased TLR4 signaling in intestinal mucosa.

PMID- 27875108
TI  - Scrub Typhus Leading to Acute Encephalitis Syndrome, Assam, India.
AB  - To determine the contribution of Orientia tsutsugamushi, the agent of scrub
      typhus, as a cause of acute encephalitis syndrome (AES) in Assam, India, we
      conducted a retrospective study of hospital patients with symptoms of AES during
      2013-2015. Our findings suggest that O. tsutsugamushi infection leads to AES and
      the resulting illness and death.

PMID- 27875109
TI  - Novel Reassortant Clade 2.3.4.4 Avian Influenza A(H5N8) Virus in Wild Aquatic
      Birds, Russia, 2016.
AB  - The emergence of novel avian influenza viruses in migratory birds is of concern
      because of the potential for virus dissemination during fall migration. We report
      the identification of novel highly pathogenic avian influenza viruses of subtype
      H5N8, clade 2.3.4.4, and their reassortment with other avian influenza viruses in
      waterfowl and shorebirds of Siberia.

PMID- 27875110
TI  - Low Circulation of Zika Virus, Cambodia, 2007-2016.
AB  - We describe a retrospective study on circulation of Zika virus in Cambodia during
      2007-2016 among patients with dengue-like symptoms and Aedes aegypti mosquitoes.
      Our findings suggest that Zika virus in Cambodia belongs to the Asia genotype, is
      endemic, has low prevalence, and has had low-level impact on public health.

PMID- 27875111
TI  - Improving Rural Health: How system-level innovation and policy reform can enhance
      health outcomes across the United States.
AB  - The United States is hailed as providing the most advanced health care the world
      has to offer. With cutting-edge medical devices, groundbreaking procedures, and
      innovative technologies, our hospitals and medical centers define what the global
      community sees as modern biomedicine. Engineers and clinicians continue to push
      and reshape this standard with new inventions enabled by a rapidly developing
      knowledge base. However, the fruit of this advancement has not benefited
      Americans equally. Millions still face significant obstacles to access health
      care, and our rural communities in particular have been left behind (see also
      "The Challenge of Rural Health Care").

PMID- 27875112
TI  - Tying Tech to Care: Connected health is better for both providers and patients.
AB  - People can do an incredible range of things remotely today. From a chair at the
      office or under an umbrella at the beach, they can adjust lights and appliance
      settings at home, monitor visitors on their doorstep, and check in on their
      teenagers? whereabouts. When it comes to health care, however, there?s still a
      long way to go before patients can get even simple care advice without having to
      make an appointment and trudge into the clinic or doctor's office.

PMID- 27875113
TI  - mHealth to the Rescue: Growing use of wireless and mobile technologies improves
      community health, even in rural areas.
AB  - In rural areas, it is not unusual for patients to travel 50 miles or more to
      reach their doctors? offices or for doctors to refer patients to specialists
      whose offices are 80, 100, even 200-plus miles away. The sheer distance is a
      major obstacle for patients of all kinds: those who need urgent specialist care,
      those who have a chronic condition that requires regular visits, those who live
      in areas prone to poor weather-related driving conditions-really, anyone who has
      better things to do than spend hours traveling to and from a medical appointment.

PMID- 27875114
TI  - Technological Innovation Comes to Palliative Care: With a shortage of palliative
      specialists, telemedicine and remote monitoring offer relief.
AB  - At first, palliative care and technology might seem like strange bedfellows. At
      its core, palliative care is a very human side of medicine, relying heavily on
      talking with and listening to people to understand their experiences and goals.
      Technology, on the other hand, can often feel impersonal, cold, and one-size
      fitsall. Despite this apparent disconnect, researchers and clinicians are finding
      new ways to harness technology to facilitate communication between patients and
      caregivers.

PMID- 27875115
TI  - Target Malaria Has a Killer in Its Sights: Eliminating the world?s deadliest
      disease has been a priority for decades, and, thanks to innovative gene-drive
      technology, Target Malaria is getting closer to achieving that goal.
AB  - The mosquito is the deadliest animal in the world (Figure 1). It is the main
      carrier of parasites that cause malaria, which is a bigger killer than any other
      disease in history; in fact, some blame malaria for the deaths of half the humans
      who have ever lived. Today, malaria continues to have a devastating effect on the
      health of millions of people.

PMID- 27875116
TI  - Toward a Comprehensive Cure: Digital information and communication technology is
      helping to meet health care challenges in India.
AB  - How would you provide effective and affordable health care in a country of more
      than 1.25 billion where there are only 0.7 physicians for every 1,000 people [1]?
      The Revised National Tuberculosis Control Program (RNTCP) and the Karnataka
      Internet-Assisted Diagnosis of Retinopathy of Prematurity (KIDROP) service are
      two notable efforts designed to deliver care across India, in both urban and
      rural areas and from the country?s flat plains to its rugged mountainous and
      desert regions.

PMID- 27875117
TI  - Emotional Matters: Innovative software brings emotional intelligence to our
      digital devices.
AB  - In 1872, Charles Darwin published The Expression of the Emotions in Man and
      Animals, in which he argued that mammals show emotion reliably in their faces.
      Since then, thousands of studies have confirmed the robustness of Darwin's
      argument in many fields, including linguistics, semiotics, social psychology, and
      computer science. More interestingly, several studies, including those of
      renowned psychologist Paul Ekman, demonstrated that basic emotions are, indeed,
      universal. Affectiva, a Massachusetts Institute of Technology spinoff located in
      Waltham, Massachusetts, builds a variety of products that harness the two main
      characteristics of facial expressions-robustness and universality-to measure and
      analyze emotional responses.

PMID- 27875118
TI  - Women's Health Is Personal: More technologies by and for women are moving into
      the mainstream--thanks, in part, to personalized medicine.
AB  - One fall day in Boston, Ridhi Tariyal sat on an examination table in her primary
      care doctor's office. Her doctor sat across from her, hurriedly transcribing
      notes as Tariyal responded to the doctor's questions. It was the end of Tariyal's
      physical, and the waiting room was full. "Do you have any questions?" the doctor
      asked, not turning away from the computer screen.

PMID- 27875119
TI  - Image-Guided Interventions: We've come a long way, but are we there?
AB  - While the term "image-guided surgery" has gained popularity fairly recently, the
      use of imaging for medical interventions dates as far back as the beginning of
      the 20th century. Dr. George H. Gray of Lynn, Massachusetts, reported in his 1908
      article "X-rays in Surgical Work," published in volume 2 of the Journal of
      Therapeutics and Dietetics, that "the one great stride in the handling of
      difficult cases was the accurate diagnosis made possible by the use of the X
      rays." His story points to the day when a seamstress presented to his office with
      a broken sewing needle embedded in her hand. Thanks to the use of the recently
      discovered X-rays by Wilhelm Conrad Roentgen, the father of diagnostic radiology,
      Gray was able not only to confirm that the needle was indeed embedded in her hand
      but also to locate its parts, saving "an hour's hunting as some had previously
      done and then often failed."

PMID- 27875120
TI  - New Frontiers in Robotic Surgery: The latest high-tech surgical tools allow for
      superhuman sensing and more.
AB  - Over the past 30 years, robots have become standard fixtures in operating rooms.
      During brain surgery, a NeuroMate robot may guide a neurosurgeon to a target
      within the pulsing cortex. In orthopedics, a Mako robot sculpts and drills bone
      during knee and hip replacement surgery. Dominating the general surgery field is
      the da Vinci robot, a multiarmed device that allows surgeons to conduct precise
      movements of tools through small incisions that they could not manage with their
      own hands.

PMID- 27875121
TI  - Nikola Tesla: Why was he so much resisted and forgotten? [Retrospectroscope].
AB  - Recently, during the Christmas season, a friend of mine visited me and, sneaking
      a look at my bookshelves, found two rather old Nikola Tesla biographies, which I
      had used to prepare a "Retrospectroscope" column for the then-named IEEE
      Engineering in Medicine and Biology Magazine when our dear friend Alvin Wald was
      its editor-inchief [2]. Eighteen years have elapsed since then; soon, the idea
      came up of revamping the article. Cynthia Weber, the magazine's current associate
      editor, considered it acceptable, and here is the new note divided in two parts:
      that is, a slightly revised version of the original article followed by new
      material, including some quite interesting information regarding Tesla's homes
      and laboratories. On top of this, Tesla is not devoid of a science fiction touch,
      as mentioned at the end.

PMID- 27875122
TI  - Inferring Individual-Level Variations in the Functional Parcellation of the
      Cerebral Cortex.
AB  - OBJECTIVE: Functional parcellation of the cerebral cortex is variable across
      different subjects or between cognitive states. Ignoring individual-or state
      dependent variations in the functional parcellation may lead to inaccurate
      representations of individual functional connectivity, limiting the precision of
      interpretations of differences in individual connectivity profiles. However, it
      is difficult to infer the individual-level variations due to the relatively low
      robustness of methods for parcellation of individual subjects. METHODS: We
      propose a method called "joint K-means" to robustly parcellate the cerebral
      cortex using functional magnetic resonance imaging (fMRI) data for contrasts
      between two states or subjects that intended to characterize variance in
      individual functional parcellations. The key idea of the proposed method is to
      jointly infer parcellations in contrasted datasets by iterative descent, while
      constraining the similarity of the two pathways in searches for local minima to
      reduce spurious variations. RESULTS: Parcellations of resting-state fMRI datasets
      from the Human Connectome Project show that the similarity of parcellations for
      an individual subject studied on two sessions is greater than that between
      different subjects. Differences in parcellations between subjects are
      nonuniformly distributed across the cerebral cortex, with clusters of higher
      variance in the prefrontal, lateral temporal, and occipito-parietal cortices.
      This pattern is reproducible across sessions, between groups, and using different
      numbers of parcels. CONCLUSION: The individual-level variations inferred by the
      proposed method are plausible and consistent with the previously reported
      functional connectivity variability. SIGNIFICANCE: The proposed method is a
      promising tool for investigating relationships between the cerebral functional
      organization and behavioral differences.

PMID- 27875123
TI  - Synergetic and Redundant Information Flow Detected by Unnormalized Granger
      Causality: Application to Resting State fMRI.
AB  - OBJECTIVES: We develop a framework for the analysis of synergy and redundancy in
      the pattern of information flow between subsystems of a complex network. METHODS:
      The presence of redundancy and/or synergy in multivariate time series data
      renders difficulty to estimate the neat flow of information from each driver
      variable to a given target. We show that adopting an unnormalized definition of
      Granger causality, one may put in evidence redundant multiplets of variables
      influencing the target by maximizing the total Granger causality to a given
      target, over all the possible partitions of the set of driving variables.
      Consequently, we introduce a pairwise index of synergy which is zero when two
      independent sources additively influence the future state of the system,
      differently from previous definitions of synergy. RESULTS: We report the
      application of the proposed approach to resting state functional magnetic
      resonance imaging data from the Human Connectome Project showing that redundant
      pairs of regions arise mainly due to space contiguity and interhemispheric
      symmetry, while synergy occurs mainly between nonhomologous pairs of regions in
      opposite hemispheres. CONCLUSIONS: Redundancy and synergy, in healthy resting
      brains, display characteristic patterns, revealed by the proposed approach.
      SIGNIFICANCE: The pairwise synergy index, here introduced, maps the informational
      character of the system at hand into a weighted complex network: the same
      approach can be applied to other complex systems whose normal state corresponds
      to a balance between redundant and synergetic circuits.

PMID- 27875124
TI  - Multimodal Source Imaging: Basic Methods, Signal Processing Techniques, and
      Applications.
AB  - Multimodal source imaging is an emerging field in biomedical engineering. Its
      central goal is to combine different imaging modalities in a single model or data
      representation, such that the combination provides an enhanced insight into the
      underlying physiological organ, compared to each modality separately. It requires
      advanced signal acquisition and processing techniques and has applications in
      cognitive neuroscience, clinical neuroscience and electrocardiology. Therefore,
      it belongs to the heart of biomedical engineering.

PMID- 27875125
TI  - Time-Frequency Strategies for Increasing High-Frequency Oscillation Detectability
      in Intracerebral EEG.
AB  - BACKGROUND: High-frequency oscillations (HFOs) are considered to be highly
      representative of brain tissues capable of producing epileptic seizures. The
      visual review of HFOs on intracerebral electroencephalography is time consuming
      and tedious, and it can be improved by time-frequency (TF) analysis. The main
      issue is that the signal is dominated by lower frequencies that mask the HFOs.
      Our aim was to flatten (i.e., whiten) the frequency spectrum to enhance the fast
      oscillations while preserving an optimal signal to noise ratio (SNR). METHOD: We
      investigated eight methods of data whitening based on either prewhitening or TF
      normalization in order to improve the detectability of HFOs. We detected all
      local maxima of the TF image above a range of thresholds in the HFO band.
      RESULTS: We obtained the precision and recall curves at different SNR and for
      different HFO types and illustrate the added value of whitening both in the TF
      plane and in time domain. CONCLUSION: The normalization strategies based on a
      baseline and on our proposed method (the "H 0 z-score") are more precise than the
      others. SIGNIFICANCE: The H 0 z-score provides an optimal framework for
      representing and detecting HFOs, independent of a baseline and a priori frequency
      bands.

PMID- 27875126
TI  - Epileptogenic Source Imaging Using Cross-Frequency Coupled Signals From Scalp
      EEG.
AB  - OBJECTIVE: The epileptogenic zone (EZ) is a brain region containing the sources
      of seizure genesis. Removal of the EZ is associated with cessation of seizures
      after resective surgical procedures, as measured by Engel Class I score. This
      study describes a novel EEG (electroencephalography) source imaging (ESI) method
      which uses cross-frequency coupled potential signals (SCFC) derived from scalp
      EEG. METHODS: Scalp EEG were recorded from ten patients (20 seizures) suffering
      from epilepsy. The S CFC were constructed from the phase and amplitude of the
      lower and higher frequency rhythms at electrographic seizure onset. ESI was then
      performed using the SCFC. Validation of the technique was facilitated by forward
      and inverse computer modeling of known cortical sources, and the correspondence
      of the ESI with EZ in resected regions of patients. RESULTS: For ten seizures
      sampled at or above 500 Hz from four patients, all estimated sources lay within
      the resected region, emphasizing the clinical importance of higher sampling
      rates. The SCFC demonstrated significant advantages over the "raw" scalp EEG,
      indicating its robust noise performance. Modeling investigations indicated that a
      signal-to-noise ratio above 0.2 was sufficient to achieve successful localization
      regarding EMG artifacts. CONCLUSION: The association of the estimated sources to
      the EZ suggests that cross-frequency coupling is a feature of the brain's neural
      networks, not of artifactual activity. The SCFC can effectively extract brain
      signals from a noisy background. SIGNIFICANCE: We propose this approach to
      enhance the placement of intracranial electrode for surgical intervention.

PMID- 27875127
TI  - Focused Ultrasound Help Realize High Spatiotemporal Brain Imaging?-A Concept on
      Acousto-Electrophysiological Neuroimaging.
AB  - We present a concept for integrating focused ultrasound (FUS) with
      electrophysiological neuroimaging, in order to achieve high spatiotemporal
      resolution brain imaging. This approach, which we are tentatively calling acousto
      electrophysiological neuroimaging, leverages on the spatial focality and
      noninvasiveness of FUS and may potentially lead to a noninvasive human brain
      imaging modality with high resolution in both space and time domains. By the use
      of modulated FUS, spatial selectivity can be accomplished for high-resolution
      electrophysiological neuroimaging. Frequency shifting in resulting magnetic
      signals (using modulated FUS) may potentially open the door for a room
      temperature magnetoencephalography device.

PMID- 27875128
TI  - Toward a Robust Estimation of Respiratory Rate From Pulse Oximeters.
AB  - GOAL: Current methods for estimating respiratory rate (RR) from the
      photoplethysmogram (PPG) typically fail to distinguish between periods of high-
      and low-quality input data, and fail to perform well on independent "validation"
      datasets. The lack of robustness of existing methods directly results in a lack
      of penetration of such systems into clinical practice. The present work proposes
      an alternative method to improve the robustness of the estimation of RR from the
      PPG. METHODS: The proposed algorithm is based on the use of multiple
      autoregressive models of different orders for determining the dominant
      respiratory frequency in the three respiratory-induced variations (frequency,
      amplitude, and intensity) derived from the PPG. The algorithm was tested on two
      different datasets comprising 95 eight-minute PPG recordings (in total) acquired
      from both children and adults in different clinical settings, and its performance
      using two window sizes (32 and 64 seconds) was compared with that of existing
      methods in the literature. RESULTS: The proposed method achieved comparable
      accuracy to existing methods in the literature, with mean absolute errors
      (median, 25[Formula: see text]-75[Formula: see text] percentiles for a window
      size of 32 seconds) of 1.5 (0.3-3.3) and 4.0 (1.8-5.5) breaths per minute (for
      each dataset respectively), whilst providing RR estimates for a greater
      proportion of windows (over 90% of the input data are kept). CONCLUSION:
      Increased robustness of RR estimation by the proposed method was demonstrated.
      SIGNIFICANCE: This work demonstrates that the use of large publicly available
      datasets is essential for improving the robustness of wearable-monitoring
      algorithms for use in clinical practice.

PMID- 27875132
TI  - EMG-Driven Optimal Estimation of Subject-SPECIFIC Hill Model Muscle-Tendon
      Parameters of the Knee Joint Actuators.
AB  - OBJECTIVE: the purpose of this paper is to propose an optimal control problem
      formulation to estimate subject-specific Hill model muscle-tendon (MT-)
      parameters of the knee joint actuators by optimizing the fit between experimental
      and model-based knee moments. Additionally, this paper aims at determining which
      sets of functional motions contain the necessary information to identify the MT
      parameters. METHODS: the optimal control and parameter estimation problem
      underlying the MT-parameter estimation is solved for subject-specific MT
      parameters via direct collocation using an electromyography-driven
      musculoskeletal model. The sets of motions containing sufficient information to
      identify the MT-parameters are determined by evaluating knee moments simulated
      based on subject-specific MT-parameters against experimental moments. RESULTS:
      the MT-parameter estimation problem was solved in about 30 CPU minutes. MT
      parameters could be identified from only seven of the 62 investigated sets of
      motions, underlining the importance of the experimental protocol. Using subject
      specific MT-parameters instead of more common linearly scaled MT-parameters
      improved the fit between inverse dynamics moments and simulated moments by about
      30% in terms of the coefficient of determination (from [Formula: see text] to
      [Formula: see text]) and by about 26% in terms of the root mean square error
      (from [Formula: see text] to [Formula: see text] ). In particular, subject
      specific MT-parameters of the knee flexors were very different from linearly
      scaled MT-parameters. CONCLUSION: we introduced a computationally efficient
      optimal control problem formulation and provided guidelines for designing an
      experimental protocol to estimate subject-specific MT-parameters improving the
      accuracy of motion simulations. SIGNIFICANCE: the proposed formulation opens new
      perspectives for subject-specific musculoskeletal modeling, which might be
      beneficial for simulating and understanding pathological motions.

PMID- 27875134
TI  - Squares: Supporting Interactive Performance Analysis for Multiclass Classifiers.
AB  - Performance analysis is critical in applied machine learning because it
      influences the models practitioners produce. Current performance analysis tools
      suffer from issues including obscuring important characteristics of model
      behavior and dissociating performance from data. In this work, we present
      Squares, a performance visualization for multiclass classification problems.
      Squares supports estimating common performance metrics while displaying instance
      level distribution information necessary for helping practitioners prioritize
      efforts and access data. Our controlled study shows that practitioners can assess
      performance significantly faster and more accurately with Squares than a
      confusion matrix, a common performance analysis tool in machine learning.

PMID- 27875133
TI  - Bipolar Intracardiac Electrogram Active Interval Extraction During Atrial
      Fibrillation.
AB  - OBJECTIVE: We introduce novel methods to identify the active intervals (AIs) of
      intracardiac electrograms (IEGMs) during complex arrhythmias, such as atrial
      fibrillation (AF). METHODS: We formulate the AI extraction problem, which
      consists of estimating the beginning and duration of the AIs, as a sequence of
      hypothesis tests. In each test, we compare the variance of a small portion of the
      bipolar IEGM with its adjacent segments. We propose modified general-likelihood
      ratio (MGLR) and separating-function-estimation tests; we derive five test
      statistics (TSs), and show that the AIs can be obtained by threshold crossing the
      TSs. We apply the proposed methods to the IEGM segments collected from the left
      atrium of 16 patients (62.4 +/- 8.2-years old, four females, four paroxysmal, and
      twelve persistent AF) prior to catheter ablation. The accuracy of our methods is
      evaluated by comparing them with previously developed methods and manual
      annotation (MA). RESULTS: Our results show a high level of similarity between the
      AIs of the proposed methods and MA, e.g., the true and false positive rates of
      one of the MGLR-based methods were, respectively, 97.8% and 1.4%. The mean
      absolute error from estimation of the onset and end of AIs and also for the
      estimation of the mean cycle length for that approach was 8.7 +/- 10.5, 13 +/-
      15.5, and 4.2 +/- 9.4 ms, respectively. CONCLUSION: The proposed methods can
      accurately identify onset and duration of AI of the IEGM during AF. SIGNIFICANCE:
      The proposed methods can be used for real-time automated analysis of AF, the most
      challenging complex arrhythmia.

PMID- 27875135
TI  - An Analysis of Machine- and Human-Analytics in Classification.
AB  - In this work, we present a study that traces the technical and cognitive
      processes in two visual analytics applications to a common theoretic model of
      soft knowledge that may be added into a visual analytics process for constructing
      a decision-tree model. Both case studies involved the development of
      classification models based on the "bag of features" approach. Both compared a
      visual analytics approach using parallel coordinates with a machine-learning
      approach using information theory. Both found that the visual analytics approach
      had some advantages over the machine learning approach, especially when sparse
      datasets were used as the ground truth. We examine various possible factors that
      may have contributed to such advantages, and collect empirical evidence for
      supporting the observation and reasoning of these factors. We propose an
      information-theoretic model as a common theoretic basis to explain the phenomena
      exhibited in these two case studies. Together we provide interconnected empirical
      and theoretical evidence to support the usefulness of visual analytics.

PMID- 27875136
TI  - Multi-Resolution Climate Ensemble Parameter Analysis with Nested Parallel
      Coordinates Plots.
AB  - Due to the uncertain nature of weather prediction, climate simulations are
      usually performed multiple times with different spatial resolutions. The outputs
      of simulations are multi-resolution spatial temporal ensembles. Each simulation
      run uses a unique set of values for multiple convective parameters. Distinct
      parameter settings from different simulation runs in different resolutions
      constitute a multi-resolution high-dimensional parameter space. Understanding the
      correlation between the different convective parameters, and establishing a
      connection between the parameter settings and the ensemble outputs are crucial to
      domain scientists. The multi-resolution high-dimensional parameter space,
      however, presents a unique challenge to the existing correlation visualization
      techniques. We present Nested Parallel Coordinates Plot (NPCP), a new type of
      parallel coordinates plots that enables visualization of intra-resolution and
      inter-resolution parameter correlations. With flexible user control, NPCP
      integrates superimposition, juxtaposition and explicit encodings in a single view
      for comparative data visualization and analysis. We develop an integrated visual
      analytics system to help domain scientists understand the connection between
      multi-resolution convective parameters and the large spatial temporal ensembles.
      Our system presents intricate climate ensembles with a comprehensive overview and
      on-demand geographic details. We demonstrate NPCP, along with the climate
      ensemble visualization system, based on real-world use-cases from our
      collaborators in computational and predictive science.

PMID- 27875137
TI  - Visualizing the Hidden Activity of Artificial Neural Networks.
AB  - In machine learning, pattern classification assigns high-dimensional vectors
      (observations) to classes based on generalization from examples. Artificial
      neural networks currently achieve state-of-the-art results in this task. Although
      such networks are typically used as black-boxes, they are also widely believed to
      learn (high-dimensional) higher-level representations of the original
      observations. In this paper, we propose using dimensionality reduction for two
      tasks: visualizing the relationships between learned representations of
      observations, and visualizing the relationships between artificial neurons.
      Through experiments conducted in three traditional image classification benchmark
      datasets, we show how visualization can provide highly valuable feedback for
      network designers. For instance, our discoveries in one of these datasets (SVHN)
      include the presence of interpretable clusters of learned representations, and
      the partitioning of artificial neurons into groups with apparently related
      discriminative roles.

PMID- 27875138
TI  - TopicLens: Efficient Multi-Level Visual Topic Exploration of Large-Scale Document
      Collections.
AB  - Topic modeling, which reveals underlying topics of a document corpus, has been
      actively adopted in visual analytics for large-scale document collections.
      However, due to its significant processing time and non-interactive nature, topic
      modeling has so far not been tightly integrated into a visual analytics workflow.
      Instead, most such systems are limited to utilizing a fixed, initial set of
      topics. Motivated by this gap in the literature, we propose a novel interaction
      technique called TopicLens that allows a user to dynamically explore data through
      a lens interface where topic modeling and the corresponding 2D embedding are
      efficiently computed on the fly. To support this interaction in real time while
      maintaining view consistency, we propose a novel efficient topic modeling method
      and a semi-supervised 2D embedding algorithm. Our work is based on improving
      state-of-the-art methods such as nonnegative matrix factorization and t
      distributed stochastic neighbor embedding. Furthermore, we have built a web-based
      visual analytics system integrated with TopicLens. We use this system to measure
      the performance and the visualization quality of our proposed methods. We provide
      several scenarios showcasing the capability of TopicLens using real-world
      datasets.

PMID- 27875139
TI  - TextTile: An Interactive Visualization Tool for Seamless Exploratory Analysis of
      Structured Data and Unstructured Text.
AB  - We describe TextTile, a data visualization tool for investigation of datasets and
      questions that require seamless and flexible analysis of structured data and
      unstructured text. TextTile is based on real-world data analysis problems
      gathered through our interaction with a number of domain experts and provides a
      general purpose solution to such problems. The system integrates a set of
      operations that can interchangeably be applied to the structured as well as to
      unstructured text part of the data to generate useful data summaries. Such
      summaries are then organized in visual tiles in a grid layout to allow their
      analysis and comparison. We validate TextTile with task analysis, use cases and a
      user study showing the system can be easily learned and proficiently used to
      carry out nontrivial tasks.

PMID- 27875140
TI  - VisMatchmaker: Cooperation of the User and the Computer in Centralized Matching
      Adjustment.
AB  - Centralized matching is a ubiquitous resource allocation problem. In a
      centralized matching problem, each agent has a preference list ranking the other
      agents and a central planner is responsible for matching the agents manually or
      with an algorithm. While algorithms can find a matching which optimizes some
      performance metrics, they are used as a black box and preclude the central
      planner from applying his domain knowledge to find a matching which aligns better
      with the user tasks. Furthermore, the existing matching visualization techniques
      (i.e. bipartite graph and adjacency matrix) fail in helping the central planner
      understand the differences between matchings. In this paper, we present
      VisMatchmaker, a visualization system which allows the central planner to explore
      alternatives to an algorithm-generated matching. We identified three common tasks
      in the process of matching adjustment: problem detection, matching recommendation
      and matching evaluation. We classified matching comparison into three levels and
      designed visualization techniques for them, including the number line view and
      the stacked graph view. Two types of algorithmic support, namely direct
      assignment and range search, and their interactive operations are also provided
      to enable the user to apply his domain knowledge in matching adjustment.

PMID- 27875141
TI  - Visual Interaction with Dimensionality Reduction: A Structured Literature
      Analysis.
AB  - Dimensionality Reduction (DR) is a core building block in visualizing
      multidimensional data. For DR techniques to be useful in exploratory data
      analysis, they need to be adapted to human needs and domain-specific problems,
      ideally, interactively, and on-the-fly. Many visual analytics systems have
      already demonstrated the benefits of tightly integrating DR with interactive
      visualizations. Nevertheless, a general, structured understanding of this
      integration is missing. To address this, we systematically studied the visual
      analytics and visualization literature to investigate how analysts interact with
      automatic DR techniques. The results reveal seven common interaction scenarios
      that are amenable to interactive control such as specifying algorithmic
      constraints, selecting relevant features, or choosing among several DR
      algorithms. We investigate specific implementations of visual analysis systems
      integrating DR, and analyze ways that other machine learning methods have been
      combined with DR. Summarizing the results in a "human in the loop" process model
      provides a general lens for the evaluation of visual interactive DR systems. We
      apply the proposed model to study and classify several systems previously
      described in the literature, and to derive future research opportunities.

PMID- 27875142
TI  - VisFlow - Web-based Visualization Framework for Tabular Data with a Subset Flow
      Model.
AB  - Data flow systems allow the user to design a flow diagram that specifies the
      relations between system components which process, filter or visually present the
      data. Visualization systems may benefit from user-defined data flows as an
      analysis typically consists of rendering multiple plots on demand and performing
      different types of interactive queries across coordinated views. In this paper,
      we propose VisFlow, a web-based visualization framework for tabular data that
      employs a specific type of data flow model called the subset flow model. VisFlow
      focuses on interactive queries within the data flow, overcoming the limitation of
      interactivity from past computational data flow systems. In particular, VisFlow
      applies embedded visualizations and supports interactive selections, brushing and
      linking within a visualization-oriented data flow. The model requires all data
      transmitted by the flow to be a data item subset (i.e. groups of table rows) of
      some original input table, so that rendering properties can be assigned to the
      subset unambiguously for tracking and comparison. VisFlow features the analysis
      flexibility of a flow diagram, and at the same time reduces the diagram
      complexity and improves usability. We demonstrate the capability of VisFlow on
      two case studies with domain experts on real-world datasets showing that VisFlow
      is capable of accomplishing a considerable set of visualization and analysis
      tasks. The VisFlow system is available as open source on GitHub.

PMID- 27875143
TI  - Annotation Graphs: A Graph-Based Visualization for Meta-Analysis of Data Based on
      User-Authored Annotations.
AB  - User-authored annotations of data can support analysts in the activity of
      hypothesis generation and sensemaking, where it is not only critical to document
      key observations, but also to communicate insights between analysts. We present
      annotation graphs, a dynamic graph visualization that enables meta-analysis of
      data based on user-authored annotations. The annotation graph topology encodes
      annotation semantics, which describe the content of and relations between data
      selections, comments, and tags. We present a mixed-initiative approach to graph
      layout that integrates an analyst's manual manipulations with an automatic method
      based on similarity inferred from the annotation semantics. Various visual graph
      layout styles reveal different perspectives on the annotation semantics.
      Annotation graphs are implemented within C8, a system that supports authoring
      annotations during exploratory analysis of a dataset. We apply principles of
      Exploratory Sequential Data Analysis (ESDA) in designing C8, and further link
      these to an existing task typology in the visualization literature. We develop
      and evaluate the system through an iterative user-centered design process with
      three experts, situated in the domain of analyzing HCI experiment data. The
      results suggest that annotation graphs are effective as a method of visually
      extending user-authored annotations to data meta-analysis for discovery and
      organization of ideas.

PMID- 27875144
TI  - What do Constraint Programming Users Want to See? Exploring the Role of
      Visualisation in Profiling of Models and Search.
AB  - Constraint programming allows difficult combinatorial problems to be modelled
      declaratively and solved automatically. Advances in solver technologies over
      recent years have allowed the successful use of constraint programming in many
      application areas. However, when a particular solver's search for a solution
      takes too long, the complexity of the constraint program execution hinders the
      programmer's ability to profile that search and understand how it relates to
      their model. Therefore, effective tools to support such profiling and allow users
      of constraint programming technologies to refine their model or experiment with
      different search parameters are essential. This paper details the first user
      centred design process for visual profiling tools in this domain. We report on:
      our insights and opportunities identified through an on-line questionnaire and a
      creativity workshop with domain experts carried out to elicit requirements for
      analytical and visual profiling techniques; our designs and functional prototypes
      realising such techniques; and case studies demonstrating how these techniques
      shed light on the behaviour of the solvers in practice.

PMID- 27875145
TI  - ViDX: Visual Diagnostics of Assembly Line Performance in Smart Factories.
AB  - Visual analytics plays a key role in the era of connected industry (or industry
      4.0, industrial internet) as modern machines and assembly lines generate large
      amounts of data and effective visual exploration techniques are needed for
      troubleshooting, process optimization, and decision making. However, developing
      effective visual analytics solutions for this application domain is a challenging
      task due to the sheer volume and the complexity of the data collected in the
      manufacturing processes. We report the design and implementation of a
      comprehensive visual analytics system, ViDX. It supports both real-time tracking
      of assembly line performance and historical data exploration to identify
      inefficiencies, locate anomalies, and form hypotheses about their causes and
      effects. The system is designed based on a set of requirements gathered through
      discussions with the managers and operators from manufacturing sites. It features
      interlinked views displaying data at different levels of detail. In particular,
      we apply and extend the Marey's graph by introducing a time-aware outlier
      preserving visual aggregation technique to support effective troubleshooting in
      manufacturing processes. We also introduce two novel interaction techniques,
      namely the quantiles brush and samples brush, for the users to interactively
      steer the outlier detection algorithms. We evaluate the system with example use
      cases and an in-depth user interview, both conducted together with the managers
      and operators from manufacturing plants. The result demonstrates its
      effectiveness and reports a successful pilot application of visual analytics for
      manufacturing in smart factories.

PMID- 27875146
TI  - Visual Analytics for Mobile Eye Tracking.
AB  - The analysis of eye tracking data often requires the annotation of areas of
      interest (AOIs) to derive semantic interpretations of human viewing behavior
      during experiments. This annotation is typically the most time-consuming step of
      the analysis process. Especially for data from wearable eye tracking glasses,
      every independently recorded video has to be annotated individually and
      corresponding AOIs between videos have to be identified. We provide a novel
      visual analytics approach to ease this annotation process by image-based,
      automatic clustering of eye tracking data integrated in an interactive labeling
      and analysis system. The annotation and analysis are tightly coupled by multiple
      linked views that allow for a direct interpretation of the labeled data in the
      context of the recorded video stimuli. The components of our analytics
      environment were developed with a user-centered design approach in close
      cooperation with an eye tracking expert. We demonstrate our approach with eye
      tracking data from a real experiment and compare it to an analysis of the data by
      manual annotation of dynamic AOIs. Furthermore, we conducted an expert user study
      with 6 external eye tracking researchers to collect feedback and identify
      analysis strategies they used while working with our application.

PMID- 27875147
TI  - GazeDx: Interactive Visual Analytics Framework for Comparative Gaze Analysis with
      Volumetric Medical Images.
AB  - We present an interactive visual analytics framework, GazeDx (abbr. of
      GazeDiagnosis), for the comparative analysis of gaze data from multiple readers
      examining volumetric images while integrating important contextual information
      with the gaze data. Gaze pattern comparison is essential to understanding how
      radiologists examine medical images, and to identifying factors influencing the
      examination. Most prior work depended upon comparisons with manually juxtaposed
      static images of gaze tracking results. Comparative gaze analysis with volumetric
      images is more challenging due to the additional cognitive load on 3D perception.
      A recent study proposed a visualization design based on direct volume rendering
      (DVR) for visualizing gaze patterns in volumetric images; however, effective and
      comprehensive gaze pattern comparison is still challenging due to a lack of
      interactive visualization tools for comparative gaze analysis. We take the
      challenge with GazeDx while integrating crucial contextual information such as
      pupil size and windowing into the analysis process for more in-depth and
      ecologically valid findings. Among the interactive visualization components in
      GazeDx, a context-embedded interactive scatterplot is especially designed to help
      users examine abstract gaze data in diverse contexts by embedding medical imaging
      representations well known to radiologists in it. We present the results from two
      case studies with two experienced radiologists, where they compared the gaze
      patterns of 14 radiologists reading two patients' volumetric CT images.

PMID- 27875148
TI  - Patterns and Sequences: Interactive Exploration of Clickstreams to Understand
      Common Visitor Paths.
AB  - Modern web clickstream data consists of long, high-dimensional sequences of
      multivariate events, making it difficult to analyze. Following the overarching
      principle that the visual interface should provide information about the dataset
      at multiple levels of granularity and allow users to easily navigate across these
      levels, we identify four levels of granularity in clickstream analysis: patterns,
      segments, sequences and events. We present an analytic pipeline consisting of
      three stages: pattern mining, pattern pruning and coordinated exploration between
      patterns and sequences. Based on this approach, we discuss properties of maximal
      sequential patterns, propose methods to reduce the number of patterns and
      describe design considerations for visualizing the extracted sequential patterns
      and the corresponding raw sequences. We demonstrate the viability of our approach
      through an analysis scenario and discuss the strengths and limitations of the
      methods based on user feedback.

PMID- 27875149
TI  - Visualization by Demonstration: An Interaction Paradigm for Visual Data
      Exploration.
AB  - Although data visualization tools continue to improve, during the data
      exploration process many of them require users to manually specify visualization
      techniques, mappings, and parameters. In response, we present the Visualization
      by Demonstration paradigm, a novel interaction method for visual data
      exploration. A system which adopts this paradigm allows users to provide visual
      demonstrations of incremental changes to the visual representation. The system
      then recommends potential transformations (Visual Representation, Data Mapping,
      Axes, and View Specification transformations) from the given demonstrations. The
      user and the system continue to collaborate, incrementally producing more
      demonstrations and refining the transformations, until the most effective
      possible visualization is created. As a proof of concept, we present VisExemplar,
      a mixed-initiative prototype that allows users to explore their data by
      recommending appropriate transformations in response to the given demonstrations.

PMID- 27875150
TI  - Vega-Lite: A Grammar of Interactive Graphics.
AB  - We present Vega-Lite, a high-level grammar that enables rapid specification of
      interactive data visualizations. Vega-Lite combines a traditional grammar of
      graphics, providing visual encoding rules and a composition algebra for layered
      and multi-view displays, with a novel grammar of interaction. Users specify
      interactive semantics by composing selections. In Vega-Lite, a selection is an
      abstraction that defines input event processing, points of interest, and a
      predicate function for inclusion testing. Selections parameterize visual
      encodings by serving as input data, defining scale extents, or by driving
      conditional logic. The Vega-Lite compiler automatically synthesizes requisite
      data flow and event handling logic, which users can override for further
      customization. In contrast to existing reactive specifications, Vega-Lite
      selections decompose an interaction design into concise, enumerable semantic
      units. We evaluate Vega-Lite through a range of examples, demonstrating succinct
      specification of both customized interaction methods and common techniques such
      as panning, zooming, and linked selection.

PMID- 27875151
TI  - HindSight: Encouraging Exploration through Direct Encoding of Personal
      Interaction History.
AB  - Physical and digital objects often leave markers of our use. Website links turn
      purple after we visit them, for example, showing us information we have yet to
      explore. These "footprints" of interaction offer substantial benefits in
      information saturated environments - they enable us to easily revisit old
      information, systematically explore new information, and quickly resume tasks
      after interruption. While applying these design principles have been successful
      in HCI contexts, direct encodings of personal interaction history have received
      scarce attention in data visualization. One reason is that there is little
      guidance for integrating history into visualizations where many visual channels
      are already occupied by data. More importantly, there is not firm evidence that
      making users aware of their interaction history results in benefits with regards
      to exploration or insights. Following these observations, we propose HindSight -
      an umbrella term for the design space of representing interaction history
      directly in existing data visualizations. In this paper, we examine the value of
      HindSight principles by augmenting existing visualizations with visual indicators
      of user interaction history (e.g. How the Recession Shaped the Economy in 255
      Charts, NYTimes). In controlled experiments of over 400 participants, we found
      that HindSight designs generally encouraged people to visit more data and recall
      different insights after interaction. The results of our experiments suggest that
      simple additions to visualizations can make users aware of their interaction
      history, and that these additions significantly impact users' exploration and
      insights.

PMID- 27875152
TI  - PowerSet: A Comprehensive Visualization of Set Intersections.
AB  - When analyzing a large amount of data, analysts often define groups over data
      elements that share certain properties. Using these groups as the unit of
      analysis not only reduces the data volume, but also allows detecting various
      patterns in the data. This involves analyzing intersection relations between
      these groups, and how the element attributes vary between these intersections.
      This kind of set-based analysis has various applications in a variety of domains,
      due to the generic and powerful notion of sets. However, visualizing
      intersections relations is challenging because their number grows exponentially
      with the number of sets. We present a novel technique based on Treemaps to
      provide a comprehensive overview of non-empty intersections in a set system in a
      scalable way. It enables gaining insight about how elements are distributed
      across these intersections as well as performing fine-grained analysis to explore
      and compare their attributes both in overview and in detail. Interaction allows
      querying and filtering these elements based on their set memberships. We
      demonstrate how our technique supports various use cases in data exploration and
      analysis by providing insights into set-based data, beyond the limits of state-of
      the-art techniques.

PMID- 27875153
TI  - Quantifying the Visual Impact of Classification Boundaries in Choropleth Maps.
AB  - One critical visual task when using choropleth maps is to identify spatial
      clusters in the data. If spatial units have the same color and are in the same
      neighborhood, this region can be visually identified as a spatial cluster.
      However, the choice of classification method used to create the choropleth map
      determines the visual output. The critical map elements in the classification
      scheme are those that lie near the classification boundary as those elements
      could potentially belong to different classes with a slight adjustment of the
      classification boundary. Thus, these elements have the most potential to impact
      the visual features (i.e., spatial clusters) that occur in the choropleth map. We
      present a methodology to enable analysts and designers to identify spatial
      regions where the visual appearance may be the result of spurious data artifacts.
      The proposed methodology automatically detects the critical boundary cases that
      can impact the overall visual presentation of the choropleth map using a
      classification metric of cluster stability. The map elements that belong to a
      critical boundary case are then automatically assessed to quantify the visual
      impact of classification edge effects. Our results demonstrate the impact of
      boundary elements on the resulting visualization and suggest that special
      attention should be given to these elements during map design.

PMID- 27875154
TI  - Small Multiples with Gaps.
AB  - Small multiples enable comparison by providing different views of a single data
      set in a dense and aligned manner. A common frame defines each view, which varies
      based upon values of a conditioning variable. An increasingly popular use of this
      technique is to project two-dimensional locations into a gridded space (e.g. grid
      maps), using the underlying distribution both as the conditioning variable and to
      determine the grid layout. Using whitespace in this layout has the potential to
      carry information, especially in a geographic context. Yet, the effects of doing
      so on the spatial properties of the original units are not understood. We explore
      the design space offered by such small multiples with gaps. We do so by
      constructing a comprehensive suite of metrics that capture properties of the
      layout used to arrange the small multiples for comparison (e.g. compactness and
      alignment) and the preservation of the original data (e.g. distance, topology and
      shape). We study these metrics in geographic data sets with varying properties
      and numbers of gaps. We use simulated annealing to optimize for each metric and
      measure the effects on the others. To explore these effects systematically, we
      take a new approach, developing a system to visualize this design space using a
      set of interactive matrices. We find that adding small amounts of whitespace to
      small multiple arrays improves some of the characteristics of 2D layouts, such as
      shape, distance and direction. This comes at the cost of other metrics, such as
      the retention of topology. Effects vary according to the input maps, with degree
      of variation in size of input regions found to be a factor. Optima exist for
      particular metrics in many cases, but at different amounts of whitespace for
      different maps. We suggest multiple metrics be used in optimized layouts, finding
      topology to be a primary factor in existing manually-crafted solutions, followed
      by a trade-off between shape and displacement. But the rich range of possible
      optimized layouts leads us to challenge single-solution thinking; we suggest to
      consider alternative optimized layouts for small multiples with gaps. Key to our
      work is the systematic, quantified and visual approach to exploring design spaces
      when facing a trade-off between many competing criteria-an approach likely to be
      of value to the analysis of other design spaces.

PMID- 27875155
TI  - Map LineUps: Effects of spatial structure on graphical inference.
AB  - Fundamental to the effective use of visualization as an analytic and descriptive
      tool is the assurance that presenting data visually provides the capability of
      making inferences from what we see. This paper explores two related approaches to
      quantifying the confidence we may have in making visual inferences from mapped
      geospatial data. We adapt Wickham et al.'s 'Visual Line-up' method as a direct
      analogy with Null Hypothesis Significance Testing (NHST) and propose a new
      approach for generating more credible spatial null hypotheses. Rather than using
      as a spatial null hypothesis the unrealistic assumption of complete spatial
      randomness, we propose spatially autocorrelated simulations as alternative nulls.
      We conduct a set of crowdsourced experiments (n=361) to determine the just
      noticeable difference (JND) between pairs of choropleth maps of geographic units
      controlling for spatial autocorrelation (Moran's I statistic) and geometric
      configuration (variance in spatial unit area). Results indicate that people's
      abilities to perceive differences in spatial autocorrelation vary with baseline
      autocorrelation structure and the geometric configuration of geographic units.
      These results allow us, for the first time, to construct a visual equivalent of
      statistical power for geospatial data. Our JND results add to those provided in
      recent years by Klippel et al. (2011), Harrison et al. (2014) and Kay & Heer
      (2015) for correlation visualization. Importantly, they provide an empirical
      basis for an improved construction of visual line-ups for maps and the
      development of theory to inform geospatial tests of graphical inference.

PMID- 27875156
TI  - Evaluation of Graph Sampling: A Visualization Perspective.
AB  - Graph sampling is frequently used to address scalability issues when analyzing
      large graphs. Many algorithms have been proposed to sample graphs, and the
      performance of these algorithms has been quantified through metrics based on
      graph structural properties preserved by the sampling: degree distribution,
      clustering coefficient, and others. However, a perspective that is missing is the
      impact of these sampling strategies on the resultant visualizations. In this
      paper, we present the results of three user studies that investigate how sampling
      strategies influence node-link visualizations of graphs. In particular, five
      sampling strategies widely used in the graph mining literature are tested to
      determine how well they preserve visual features in node-link diagrams. Our
      results show that depending on the sampling strategy used different visual
      features are preserved. These results provide a complimentary view to metric
      evaluations conducted in the graph mining literature and provide an impetus to
      conduct future visualization studies.

PMID- 27875157
TI  - Many-to-Many Geographically-Embedded Flow Visualisation: An Evaluation.
AB  - Showing flows of people and resources between multiple geographic locations is a
      challenging visualisation problem. We conducted two quantitative user studies to
      evaluate different visual representations for such dense many-to-many flows. In
      our first study we compared a bundled node-link flow map representation and OD
      Maps [37] with a new visualisation we call MapTrix. Like OD Maps, MapTrix
      overcomes the clutter associated with a traditional flow map while providing
      geographic embedding that is missing in standard OD matrix representations. We
      found that OD Maps and MapTrix had similar performance while bundled node-link
      flow map representations did not scale at all well. Our second study compared
      participant performance with OD Maps and MapTrix on larger data sets. Again
      performance was remarkably similar.

PMID- 27875158
TI  - An Evaluation of Visual Search Support in Maps.
AB  - Visual search can be time-consuming, especially if the scene contains a large
      number of possibly relevant objects. An instance of this problem is present when
      using geographic or schematic maps with many different elements representing
      cities, streets, sights, and the like. Unless the map is well-known to the
      reader, the full map or at least large parts of it must be scanned to find the
      elements of interest. In this paper, we present a controlled eye-tracking study
      (30 participants) to compare four variants of map annotation with labels: within
      image annotations, grid reference annotation, directional annotation, and
      miniature annotation. Within-image annotation places labels directly within the
      map without any further search support. Grid reference annotation corresponds to
      the traditional approach known from atlases. Directional annotation utilizes a
      label in combination with an arrow pointing in the direction of the label within
      the map. Miniature annotation shows a miniature grid to guide the reader to the
      area of the map in which the label is located. The study results show that within
      image annotation is outperformed by all other annotation approaches. Best task
      completion times are achieved with miniature annotation. The analysis of eye
      movement data reveals that participants applied significantly different visual
      task solution strategies for the different visual annotations.

PMID- 27875159
TI  - Evaluating the Impact of Binning 2D Scalar Fields.
AB  - The expressiveness principle for visualization design asserts that a
      visualization should encode all of the available data, and only the available
      data, implying that continuous data types should be visualized with a continuous
      encoding channel. And yet, in many domains binning continuous data is not only
      pervasive, but it is accepted as standard practice. Prior work provides no clear
      guidance for when encoding continuous data continuously is preferable to
      employing binning techniques or how this choice affects data interpretation and
      decision making. In this paper, we present a study aimed at better understanding
      the conditions in which the expressiveness principle can or should be violated
      for visualizing continuous data. We provided participants with visualizations
      employing either continuous or binned greyscale encodings of geospatial elevation
      data and compared participants' ability to complete a wide variety of tasks. For
      various tasks, the results indicate significant differences in decision making,
      confidence in responses, and task completion time between continuous and binned
      encodings of the data. In general, participants with continuous encodings were
      faster to complete many of the tasks, but never outperformed those with binned
      encodings, while performance accuracy with binned encodings was superior to
      continuous encodings in some tasks. These findings suggest that strict adherence
      to the expressiveness principle is not always advisable. We discuss both the
      implications and limitations of our results and outline various avenues for
      potential work needed to further improve guidelines for using continuous versus
      binned encodings for continuous data types.

PMID- 27875160
TI  - Immersive Collaborative Analysis of Network Connectivity: CAVE-style or Head
      Mounted Display?
AB  - High-quality immersive display technologies are becoming mainstream with the
      release of head-mounted displays (HMDs) such as the Oculus Rift. These devices
      potentially represent an affordable alternative to the more traditional,
      centralised CAVE-style immersive environments. One driver for the development of
      CAVE-style immersive environments has been collaborative sense-making. Despite
      this, there has been little research on the effectiveness of collaborative
      visualisation in CAVE-style facilities, especially with respect to abstract data
      visualisation tasks. Indeed, very few studies have focused on the use of these
      displays to explore and analyse abstract data such as networks and there have
      been no formal user studies investigating collaborative visualisation of abstract
      data in immersive environments. In this paper we present the results of the first
      such study. It explores the relative merits of HMD and CAVE-style immersive
      environments for collaborative analysis of network connectivity, a common and
      important task involving abstract data. We find significant differences between
      the two conditions in task completion time and the physical movements of the
      participants within the space: participants using the HMD were faster while the
      CAVE2 condition introduced an asymmetry in movement between collaborators.
      Otherwise, affordances for collaborative data analysis offered by the low-cost
      HMD condition were not found to be different for accuracy and communication with
      the CAVE2. These results are notable, given that the latest HMDs will soon be
      accessible (in terms of cost and potentially ubiquity) to a massive audience.

PMID- 27875162
TI  - Embedded Data Representations.
AB  - We introduce embedded data representations, the use of visual and physical
      representations of data that are deeply integrated with the physical spaces,
      objects, and entities to which the data refers. Technologies like lightweight
      wireless displays, mixed reality hardware, and autonomous vehicles are making it
      increasingly easier to display data in-context. While researchers and artists
      have already begun to create embedded data representations, the benefits, trade
      offs, and even the language necessary to describe and compare these approaches
      remain unexplored. In this paper, we formalize the notion of physical data
      referents - the real-world entities and spaces to which data corresponds - and
      examine the relationship between referents and the visual and physical
      representations of their data. We differentiate situated representations, which
      display data in proximity to data referents, and embedded representations, which
      display data so that it spatially coincides with data referents. Drawing on
      examples from visualization, ubiquitous computing, and art, we explore the role
      of spatial indirection, scale, and interaction for embedded representations. We
      also examine the tradeoffs between non-situated, situated, and embedded data
      displays, including both visualizations and physicalizations. Based on our
      observations, we identify a variety of design challenges for embedded data
      representation, and suggest opportunities for future research and applications.

PMID- 27875161
TI  - Investigating the Use of a Dynamic Physical Bar Chart for Data Exploration and
      Presentation.
AB  - Physical data representations, or data physicalizations, are a promising new
      medium to represent and communicate data. Previous work mostly studied passive
      physicalizations which require humans to perform all interactions manually.
      Dynamic shape-changing displays address this limitation and facilitate data
      exploration tasks such as sorting, navigating in data sets which exceed the fixed
      size of a given physical display, or preparing "views" to communicate insights
      about data. However, it is currently unclear how people approach and interact
      with such data representations. We ran an exploratory study to investigate how
      non-experts made use of a dynamic physical bar chart for an open-ended data
      exploration and presentation task. We asked 16 participants to explore a data set
      on European values and to prepare a short presentation of their insights using a
      physical display. We analyze: (1) users' body movements to understand how they
      approach and react to the physicalization, (2) their hand-gestures to understand
      how they interact with physical data, (3) system interactions to understand which
      subsets of the data they explored and which features they used in the process,
      and (4) strategies used to explore the data and present observations. We discuss
      the implications of our findings for the use of dynamic data physicalizations and
      avenues for future work.

PMID- 27875163
TI  - The Attraction Effect in Information Visualization.
AB  - The attraction effect is a well-studied cognitive bias in decision making
      research, where one's choice between two alternatives is influenced by the
      presence of an irrelevant (dominated) third alternative. We examine whether this
      cognitive bias, so far only tested with three alternatives and simple
      presentation formats such as numerical tables, text and pictures, also appears in
      visualizations. Since visualizations can be used to support decision making -
      e.g., when choosing a house to buy or an employee to hire - a systematic bias
      could have important implications. In a first crowdsource experiment, we indeed
      partially replicated the attraction effect with three alternatives presented as a
      numerical table, and observed similar effects when they were presented as a
      scatterplot. In a second experiment, we investigated if the effect extends to
      larger sets of alternatives, where the number of alternatives is too large for
      numerical tables to be practical. Our findings indicate that the bias persists
      for larger sets of alternatives presented as scatterplots. We discuss
      implications for future research on how to further study and possibly alleviate
      the attraction effect.

PMID- 27875164
TI  - Iterating between Tools to Create and Edit Visualizations.
AB  - A common workflow for visualization designers begins with a generative tool, like
      D3 or Processing, to create the initial visualization; and proceeds to a drawing
      tool, like Adobe Illustrator or Inkscape, for editing and cleaning.
      Unfortunately, this is typically a one-way process: once a visualization is
      exported from the generative tool into a drawing tool, it is difficult to make
      further, data-driven changes. In this paper, we propose a bridge model to allow
      designers to bring their work back from the drawing tool to re-edit in the
      generative tool. Our key insight is to recast this iteration challenge as a merge
      problem - similar to when two people are editing a document and changes between
      them need to reconciled. We also present a specific instantiation of this model,
      a tool called Hanpuku, which bridges between D3 scripts and Illustrator. We show
      several examples of visualizations that are iteratively created using Hanpuku in
      order to illustrate the flexibility of the approach. We further describe several
      hypothetical tools that bridge between other visualization tools to emphasize the
      generality of the model.

PMID- 27875165
TI  - Data-Driven Guides: Supporting Expressive Design for Information Graphics.
AB  - In recent years, there is a growing need for communicating complex data in an
      accessible graphical form. Existing visualization creation tools support
      automatic visual encoding, but lack flexibility for creating custom design; on
      the other hand, freeform illustration tools require manual visual encoding,
      making the design process time-consuming and error-prone. In this paper, we
      present Data-Driven Guides (DDG), a technique for designing expressive
      information graphics in a graphic design environment. Instead of being confined
      by predefined templates or marks, designers can generate guides from data and use
      the guides to draw, place and measure custom shapes. We provide guides to encode
      data using three fundamental visual encoding channels: length, area, and
      position. Users can combine more than one guide to construct complex visual
      structures and map these structures to data. When underlying data is changed, we
      use a deformation technique to transform custom shapes using the guides as the
      backbone of the shapes. Our evaluation shows that data-driven guides allow users
      to create expressive and more accurate custom data-driven graphics.

PMID- 27875166
TI  - Authoring Data-Driven Videos with DataClips.
AB  - Data videos, or short data-driven motion graphics, are an increasingly popular
      medium for storytelling. However, creating data videos is difficult as it
      involves pulling together a unique combination of skills. We introduce DataClips,
      an authoring tool aimed at lowering the barriers to crafting data videos.
      DataClips allows non-experts to assemble data-driven "clips" together to form
      longer sequences. We constructed the library of data clips by analyzing the
      composition of over 70 data videos produced by reputable sources such as The New
      York Times and The Guardian. We demonstrate that DataClips can reproduce over 90%
      of our data videos corpus. We also report on a qualitative study comparing the
      authoring process and outcome achieved by (1) non-experts using DataClips, and
      (2) experts using Adobe Illustrator and After Effects to create data-driven
      clips. Results indicated that non-experts are able to learn and use DataClips
      with a short training period. In the span of one hour, they were able to produce
      more videos than experts using a professional editing tool, and their clips were
      rated similarly by an independent audience.

PMID- 27875167
TI  - Temporal Summary Images: An Approach to Narrative Visualization via Interactive
      Annotation Generation and Placement.
AB  - Visualization is a powerful technique for analysis and communication of complex,
      multidimensional, and time-varying data. However, it can be difficult to manually
      synthesize a coherent narrative in a chart or graph due to the quantity of
      visualized attributes, a variety of salient features, and the awareness required
      to interpret points of interest (POls). We present Temporal Summary Images (TSIs)
      as an approach for both exploring this data and creating stories from it. As a
      visualization, a TSI is composed of three common components: (1) a temporal
      layout, (2) comic strip-style data snapshots, and (3) textual annotations. To
      augment user analysis and exploration, we have developed a number of interactive
      techniques that recommend relevant data features and design choices, including an
      automatic annotations workflow. As the analysis and visual design processes
      converge, the resultant image becomes appropriate for data storytelling. For
      validation, we use a prototype implementation for TSIs to conduct two case
      studies with large-scale, scientific simulation datasets.

PMID- 27875168
TI  - Colorgorical: Creating discriminable and preferable color palettes for
      information visualization.
AB  - We present an evaluation of Colorgorical, a web-based tool for creating
      discriminable and aesthetically preferable categorical color palettes.
      Colorgorical uses iterative semi-random sampling to pick colors from CIELAB space
      based on user-defined discriminability and preference importances. Colors are
      selected by assigning each a weighted sum score that applies the user-defined
      importances to Perceptual Distance, Name Difference, Name Uniqueness, and Pair
      Preference scoring functions, which compare a potential sample to already-picked
      palette colors. After, a color is added to the palette by randomly sampling from
      the highest scoring palettes. Users can also specify hue ranges or build off
      their own starting palettes. This procedure differs from previous approaches that
      do not allow customization (e.g., pre-made ColorBrewer palettes) or do not
      consider visualization design constraints (e.g., Adobe Color and ACE). In a
      Palette Score Evaluation, we verified that each scoring function measured
      different color information. Experiment 1 demonstrated that slider manipulation
      generates palettes that are consistent with the expected balance of
      discriminability and aesthetic preference for 3-, 5-, and 8-color palettes, and
      also shows that the number of colors may change the effectiveness of pair-based
      discriminability and preference scores. For instance, if the Pair Preference
      slider were upweighted, users would judge the palettes as more preferable on
      average. Experiment 2 compared Colorgorical palettes to benchmark palettes
      (ColorBrewer, Microsoft, Tableau, Random). Colorgorical palettes are as
      discriminable and are at least as preferable or more preferable than the
      alternative palette sets. In sum, Colorgorical allows users to make customized
      color palettes that are, on average, as effective as current industry standards
      by balancing the importance of discriminability and aesthetic preference.

PMID- 27875170
TI  - Towards Unambiguous Edge Bundling: Investigating Confluent Drawings for Network
      Visualization.
AB  - In this paper, we investigate Confluent Drawings (CD), a technique for bundling
      edges in node-link diagrams based on network connectivity. Edge-bundling
      techniques are designed to reduce edge clutter in node-link diagrams by
      coalescing lines into common paths or bundles. Unfortunately, traditional
      bundling techniques introduce ambiguity since edges are only bundled by spatial
      proximity, rather than network connectivity; following an edge from its source to
      its target can lead to the perception of incorrect connectivity if edges are not
      clearly separated within the bundles. Contrary, CDs bundle edges based on common
      sources or targets. Thus, a smooth path along a confluent bundle indicates
      precise connectivity. While CDs have been described in theory, practical
      investigation and application to real-world networks (i.e., networks beyond those
      with certain planarity restrictions) is currently lacking. Here, we provide the
      first algorithm for constructing CDs from arbitrary directed and undirected
      networks and present a simple layout method, embedded in a sand box environment
      providing techniques for interactive exploration. We then investigate patterns
      and artifacts in CDs, which we compare to other common edge-bundling techniques.
      Finally, we present the first user study that compares edge-compression
      techniques, including CD, power graphs, metro-style, and common edge bundling. We
      found that users without particular expertise in visualization or network
      analysis are able to read small CDs without difficulty. Compared to existing
      bundling techniques, CDs are more likely to allow people to correctly perceive
      connectivity.

PMID- 27875169
TI  - Probabilistic Graph Layout for Uncertain Network Visualization.
AB  - We present a novel uncertain network visualization technique based on node-link
      diagrams. Nodes expand spatially in our probabilistic graph layout, depending on
      the underlying probability distributions of edges. The visualization is created
      by computing a two-dimensional graph embedding that combines samples from the
      probabilistic graph. A Monte Carlo process is used to decompose a probabilistic
      graph into its possible instances and to continue with our graph layout
      technique. Splatting and edge bundling are used to visualize point clouds and
      network topology. The results provide insights into probability distributions for
      the entire network-not only for individual nodes and edges. We validate our
      approach using three data sets that represent a wide range of network types:
      synthetic data, protein-protein interactions from the STRING database, and travel
      times extracted from Google Maps. Our approach reveals general limitations of the
      force-directed layout and allows the user to recognize that some nodes of the
      graph are at a specific position just by chance.

PMID- 27875171
TI  - VLAT: Development of a Visualization Literacy Assessment Test.
AB  - The Information Visualization community has begun to pay attention to
      visualization literacy; however, researchers still lack instruments for measuring
      the visualization literacy of users. In order to address this gap, we
      systematically developed a visualization literacy assessment test (VLAT),
      especially for non-expert users in data visualization, by following the
      established procedure of test development in Psychological and Educational
      Measurement: (1) Test Blueprint Construction, (2) Test Item Generation, (3)
      Content Validity Evaluation, (4) Test Tryout and Item Analysis, (5) Test Item
      Selection, and (6) Reliability Evaluation. The VLAT consists of 12 data
      visualizations and 53 multiple-choice test items that cover eight data
      visualization tasks. The test items in the VLAT were evaluated with respect to
      their essentialness by five domain experts in Information Visualization and
      Visual Analytics (average content validity ratio = 0.66). The VLAT was also tried
      out on a sample of 191 test takers and showed high reliability (reliability
      coefficient omega = 0.76). In addition, we demonstrated the relationship between
      users' visualization literacy and aptitude for learning an unfamiliar
      visualization and showed that they had a fairly high positive relationship
      (correlation coefficient = 0.64). Finally, we discuss evidence for the validity
      of the VLAT and potential research areas that are related to the instrument.

PMID- 27875173
TI  - Exploring the Possibilities of Embedding Heterogeneous Data Attributes in
      Familiar Visualizations.
AB  - Heterogeneous multi-dimensional data are now sufficiently common that they can be
      referred to as ubiquitous. The most frequent approach to visualizing these data
      has been to propose new visualizations for representing these data. These new
      solutions are often inventive but tend to be unfamiliar. We take a different
      approach. We explore the possibility of extending well-known and familiar
      visualizations through including Heterogeneous Embedded Data Attributes (HEDA) in
      order to make familiar visualizations more powerful. We demonstrate how HEDA is a
      generic, interactive visualization component that can extend common visualization
      techniques while respecting the structure of the familiar layout. HEDA is a
      tabular visualization building block that enables individuals to visually
      observe, explore, and query their familiar visualizations through manipulation of
      embedded multivariate data. We describe the design space of HEDA by exploring its
      application to familiar visualizations in the D3 gallery. We characterize these
      familiar visualizations by the extent to which HEDA can facilitate data queries
      based on attribute reordering.

PMID- 27875172
TI  - booc.io: An Education System with Hierarchical Concept Maps and Dynamic Non
      linear Learning Plans.
AB  - Information hierarchies are difficult to express when real-world space or time
      constraints force traversing the hierarchy in linear presentations, such as in
      educational books and classroom courses. We present booc.io, which allows linear
      and non-linear presentation and navigation of educational concepts and material.
      To support a breadth of material for each concept, booc.io is Web based, which
      allows adding material such as lecture slides, book chapters, videos, and LTIs. A
      visual interface assists the creation of the needed hierarchical structures. The
      goals of our system were formed in expert interviews, and we explain how our
      design meets these goals. We adapt a real-world course into booc.io, and perform
      introductory qualitative evaluation with students.

PMID- 27875174
TI  - Screenit: Visual Analysis of Cellular Screens.
AB  - High-throughput and high-content screening enables large scale, cost-effective
      experiments in which cell cultures are exposed to a wide spectrum of drugs. The
      resulting multivariate data sets have a large but shallow hierarchical structure.
      The deepest level of this structure describes cells in terms of numeric features
      that are derived from image data. The subsequent level describes enveloping cell
      cultures in terms of imposed experiment conditions (exposure to drugs). We
      present Screenit, a visual analysis approach designed in close collaboration with
      screening experts. Screenit enables the navigation and analysis of multivariate
      data at multiple hierarchy levels and at multiple levels of detail. Screenit
      integrates the interactive modeling of cell physical states (phenotypes) and the
      effects of drugs on cell cultures (hits). In addition, quality control is enabled
      via the detection of anomalies that indicate low-quality data, while providing an
      interface that is designed to match workflows of screening experts. We
      demonstrate analyses for a real-world data set, CellMorph, with 6 million cells
      across 20,000 cell cultures.

PMID- 27875175
TI  - PROACT: Iterative Design of a Patient-Centered Visualization for Effective
      Prostate Cancer Health Risk Communication.
AB  - Prostate cancer is the most common cancer among men in the US, and yet most cases
      represent localized cancer for which the optimal treatment is unclear.
      Accumulating evidence suggests that the available treatment options, including
      surgery and conservative treatment, result in a similar prognosis for most men
      with localized prostate cancer. However, approximately 90% of patients choose
      surgery over conservative treatment, despite the risk of severe side effects like
      erectile dysfunction and incontinence. Recent medical research suggests that a
      key reason is the lack of patient-centered tools that can effectively communicate
      personalized risk information and enable them to make better health decisions. In
      this paper, we report the iterative design process and results of developing the
      PROgnosis Assessment for Conservative Treatment (PROACT) tool, a personalized
      health risk communication tool for localized prostate cancer patients. PROACT
      utilizes two published clinical prediction models to communicate the patients'
      personalized risk estimates and compare treatment options. In collaboration with
      the Maine Medical Center, we conducted two rounds of evaluations with prostate
      cancer survivors and urologists to identify the design elements and narrative
      structure that effectively facilitate patient comprehension under emotional
      distress. Our results indicate that visualization can be an effective means to
      communicate complex risk information to patients with low numeracy and visual
      literacy. However, the visualizations need to be carefully chosen to balance
      readability with ease of comprehension. In addition, due to patients' charged
      emotional state, an intuitive narrative structure that considers the patients'
      information need is critical to aid the patients' comprehension of their risk
      information.

PMID- 27875176
TI  - WeightLifter: Visual Weight Space Exploration for Multi-Criteria Decision Making.
AB  - A common strategy in Multi-Criteria Decision Making (MCDM) is to rank alternative
      solutions by weighted summary scores. Weights, however, are often abstract to the
      decision maker and can only be set by vague intuition. While previous work
      supports a point-wise exploration of weight spaces, we argue that MCDM can
      benefit from a regional and global visual analysis of weight spaces. Our main
      contribution is WeightLifter, a novel interactive visualization technique for
      weight-based MCDM that facilitates the exploration of weight spaces with up to
      ten criteria. Our technique enables users to better understand the sensitivity of
      a decision to changes of weights, to efficiently localize weight regions where a
      given solution ranks high, and to filter out solutions which do not rank high
      enough for any plausible combination of weights. We provide a comprehensive
      requirement analysis for weight-based MCDM and describe an interactive workflow
      that meets these requirements. For evaluation, we describe a usage scenario of
      WeightLifter in automotive engineering and report qualitative feedback from users
      of a deployed version as well as preliminary feedback from decision makers in
      multiple domains. This feedback confirms that WeightLifter increases both the
      efficiency of weight-based MCDM and the awareness of uncertainty in the ultimate
      decisions.

PMID- 27875177
TI  - Visualizing Social Media Content with SentenTree.
AB  - We introduce SentenTree, a novel technique for visualizing the content of
      unstructured social media text. SentenTree displays frequent sentence patterns
      abstracted from a corpus of social media posts. The technique employs design
      ideas from word clouds and the Word Tree, but overcomes a number of limitations
      of both those visualizations. SentenTree displays a node-link diagram where nodes
      are words and links indicate word co-occurrence within the same sentence. The
      spatial arrangement of nodes gives cues to the syntactic ordering of words while
      the size of nodes gives cues to their frequency of occurrence. SentenTree can
      help people gain a rapid understanding of key concepts and opinions in a large
      social media text collection. It is implemented as a lightweight application that
      runs in the browser.

PMID- 27875178
TI  - Optimizing Hierarchical Visualizations with the Minimum Description Length
      Principle.
AB  - In this paper we examine how the Minimum Description Length (MDL) principle can
      be used to efficiently select aggregated views of hierarchical datasets that
      feature a good balance between clutter and information. We present MDL formulae
      for generating uneven tree cuts tailored to treemap and sunburst diagrams, taking
      into account the available display space and information content of the data. We
      present the results of a proof-of-concept implementation. In addition, we
      demonstrate how such tree cuts can be used to enhance drill-down interaction in
      hierarchical visualizations by implementing our approach in an existing
      visualization tool. Validation is done with the feature congestion measure of
      clutter in views of a subset of the current DMOZ web directory, which contains
      nearly half million categories. The results show that MDL views achieve near
      constant clutter level across display resolutions. We also present the results of
      a crowdsourced user study where participants were asked to find targets in views
      of DMOZ generated by our approach and a set of baseline aggregation methods. The
      results suggest that, in some conditions, participants are able to locate targets
      (in particular, outliers) faster using the proposed approach.

PMID- 27875180
TI  - Surprise! Bayesian Weighting for De-Biasing Thematic Maps.
AB  - Thematic maps are commonly used for visualizing the density of events in spatial
      data. However, these maps can mislead by giving visual prominence to known base
      rates (such as population densities) or to artifacts of sample size and
      normalization (such as outliers arising from smaller, and thus more variable,
      samples). In this work, we adapt Bayesian surprise to generate maps that counter
      these biases. Bayesian surprise, which has shown promise for modeling human
      visual attention, weights information with respect to how it updates beliefs over
      a space of models. We introduce Surprise Maps, a visualization technique that
      weights event data relative to a set of spatia-temporal models. Unexpected events
      (those that induce large changes in belief over the model space) are visualized
      more prominently than those that follow expected patterns. Using both synthetic
      and real-world datasets, we demonstrate how Surprise Maps overcome some
      limitations of traditional event maps.

PMID- 27875179
TI  - Visplause: Visual Data Quality Assessment of Many Time Series Using Plausibility
      Checks.
AB  - Trends like decentralized energy production lead to an exploding number of time
      series from sensors and other sources that need to be assessed regarding their
      data quality (DQ). While the identification of DQ problems for such routinely
      collected data is typically based on existing automated plausibility checks, an
      efficient inspection and validation of check results for hundreds or thousands of
      time series is challenging. The main contribution of this paper is the validated
      design of Visplause, a system to support an efficient inspection of DQ problems
      for many time series. The key idea of Visplause is to utilize meta-information
      concerning the semantics of both the time series and the plausibility checks for
      structuring and summarizing results of DQ checks in a flexible way. Linked views
      enable users to inspect anomalies in detail and to generate hypotheses about
      possible causes. The design of Visplause was guided by goals derived from a
      comprehensive task analysis with domain experts in the energy sector. We reflect
      on the design process by discussing design decisions at four stages and we
      identify lessons learned. We also report feedback from domain experts after using
      Visplause for a period of one month. This feedback suggests significant
      efficiency gains for DQ assessment, increased confidence in the DQ, and the
      applicability of Visplause to summarize indicators also outside the context of
      DQ.

PMID- 27875181
TI  - Multi-Granular Trend Detection for Time-Series Analysis.
AB  - Time series (such as stock prices) and ensembles (such as model runs for weather
      forecasts) are two important types of one-dimensional time-varying data. Such
      data is readily available in large quantities but visual analysis of the raw data
      quickly becomes infeasible, even for moderately sized data sets. Trend detection
      is an effective way to simplify time-varying data and to summarize salient
      information for visual display and interactive analysis. We propose a geometric
      model for trend-detection in one-dimensional time-varying data, inspired by
      topological grouping structures for moving objects in two- or higher-dimensional
      space. Our model gives provable guarantees on the trends detected and uses three
      natural parameters: granularity, support-size, and duration. These parameters can
      be changed on-demand. Our system also supports a variety of selection brushes and
      a time-sweep to facilitate refined searches and interactive visualization of (sub
      )trends. We explore different visual styles and interactions through which
      trends, their persistence, and evolution can be explored.

PMID- 27875182
TI  - Hashedcubes: Simple, Low Memory, Real-Time Visual Exploration of Big Data.
AB  - We propose Hashedcubes, a data structure that enables real-time visual
      exploration of large datasets that improves the state of the art by virtue of its
      low memory requirements, low query latencies, and implementation simplicity. In
      some instances, Hashedcubes notably requires two orders of magnitude less space
      than recent data cube visualization proposals. In this paper, we describe the
      algorithms to build and query Hashedcubes, and how it can drive well-known
      interactive visualizations such as binned scatterplots, linked histograms and
      heatmaps. We report memory usage, build time and query latencies for a variety of
      synthetic and real-world datasets, and find that although sometimes Hashedcubes
      offers slightly slower querying times to the state of the art, the typical query
      is answered fast enough to easily sustain a interaction. In datasets with
      hundreds of millions of elements, only about 2% of the queries take longer than
      40ms. Finally, we discuss the limitations of data structure, potential spacetime
      tradeoffs, and future research directions.

PMID- 27875183
TI  - Gaussian Cubes: Real-Time Modeling for Visual Exploration of Large
      Multidimensional Datasets.
AB  - Recently proposed techniques have finally made it possible for analysts to
      interactively explore very large datasets in real time. However powerful, the
      class of analyses these systems enable is somewhat limited: specifically, one can
      only quickly obtain plots such as histograms and heatmaps. In this paper, we
      contribute Gaussian Cubes, which significantly improves on state-of-the-art
      systems by providing interactive modeling capabilities, which include but are not
      limited to linear least squares and principal components analysis (PCA). The
      fundamental insight in Gaussian Cubes is that instead of precomputing counts of
      many data subsets (as state-of-the-art systems do), Gaussian Cubes precomputes
      the best multivariate Gaussian for the respective data subsets. As an example,
      Gaussian Cubes can fit hundreds of models over millions of data points in well
      under a second, enabling novel types of visual exploration of such large
      datasets. We present three case studies that highlight the visualization and
      analysis capabilities in Gaussian Cubes, using earthquake safety simulations,
      astronomical catalogs, and transportation statistics. The dataset sizes range
      around one hundred million elements and 5 to 10 dimensions. We present extensive
      performance results, a discussion of the limitations in Gaussian Cubes, and
      future research directions.

PMID- 27875184
TI  - cite2vec: Citation-Driven Document Exploration via Word Embeddings.
AB  - Effectively exploring and browsing document collections is a fundamental problem
      in visualization. Traditionally, document visualization is based on a data model
      that represents each document as the set of its comprised words, effectively
      characterizing what the document is. In this paper we take an alternative
      perspective: motivated by the manner in which users search documents in the
      research process, we aim to visualize documents via their usage, or how documents
      tend to be used. We present a new visualization scheme - cite2vec - that allows
      the user to dynamically explore and browse documents via how other documents use
      them, information that we capture through citation contexts in a document
      collection. Starting from a usage-oriented word-document 2D projection, the user
      can dynamically steer document projections by prescribing semantic concepts, both
      in the form of phrase/document compositions and document:phrase analogies,
      enabling the exploration and comparison of documents by their use. The user
      interactions are enabled by a joint representation of words and documents in a
      common high-dimensional embedding space where user-specified concepts correspond
      to linear operations of word and document vectors. Our case studies, centered
      around a large document corpus of computer vision research papers, highlight the
      potential for usage-based document visualization.

PMID- 27875185
TI  - Molecular Surface Maps.
AB  - We present Molecular Surface Maps, a novel, view-independent, and concise
      representation for molecular surfaces. It transfers the well-known world map
      metaphor to molecular visualization. Our application maps the complex molecular
      surface to a simple 2D representation through a spherical intermediate, the
      Molecular Surface Globe. The Molecular Surface Map concisely shows arbitrary
      attributes of the original molecular surface, such as biochemical properties or
      geometrical features. This results in an intuitive overview, which allows
      researchers to assess all molecular surface attributes at a glance. Our
      representation can be used as a visual summarization of a molecule's interface
      with its environment. In particular, Molecular Surface Maps simplify the analysis
      and comparison of different data sets or points in time. Furthermore, the map
      representation can be used in a Space-time Cube to analyze time-dependent data
      from molecular simulations without the need for animation. We show the
      feasibility of Molecular Surface Maps for different typical analysis tasks of
      biomolecular data.

PMID- 27875186
TI  - Visualizing Shape Deformations with Variation of Geometric Spectrum.
AB  - This paper presents a novel approach based on spectral geometry to quantify and
      visualize non-isometric deformations of 3D surfaces by mapping two manifolds. The
      proposed method can determine multi-scale, non-isometric deformations through the
      variation of Laplace-Beltrami spectrum of two shapes. Given two triangle meshes,
      the spectra can be varied from one to another with a scale function defined on
      each vertex. The variation is expressed as a linear interpolation of eigenvalues
      of the two shapes. In each iteration step, a quadratic programming problem is
      constructed, based on our derived spectrum variation theorem and smoothness
      energy constraint, to compute the spectrum variation. The derivation of the scale
      function is the solution of such a problem. Therefore, the final scale function
      can be solved by integral of the derivation from each step, which, in turn,
      quantitatively describes non-isometric deformations between two shapes. To
      evaluate the method, we conduct extensive experiments on synthetic and real data.
      We employ real epilepsy patient imaging data to quantify the shape variation
      between the left and right hippocampi in epileptic brains. In addition, we use
      longitudinal Alzheimer data to compare the shape deformation of diseased and
      healthy hippocampus. In order to show the accuracy and effectiveness of the
      proposed method, we also compare it with spatial registration-based methods,
      e.g., non-rigid Iterative Closest Point (ICP) and voxel-based method. These
      experiments demonstrate the advantages of our method.

PMID- 27875187
TI  - Physics-Based Visual Characterization of Molecular Interaction Forces.
AB  - Molecular simulations are used in many areas of biotechnology, such as drug
      design and enzyme engineering. Despite the development of automatic computational
      protocols, analysis of molecular interactions is still a major aspect where human
      comprehension and intuition are key to accelerate, analyze, and propose
      modifications to the molecule of interest. Most visualization algorithms help the
      users by providing an accurate depiction of the spatial arrangement: the atoms
      involved in inter-molecular contacts. There are few tools that provide visual
      information on the forces governing molecular docking. However, these tools,
      commonly restricted to close interaction between atoms, do not consider whole
      simulation paths, long-range distances and, importantly, do not provide visual
      cues for a quick and intuitive comprehension of the energy functions (modeling
      intermolecular interactions) involved. In this paper, we propose visualizations
      designed to enable the characterization of interaction forces by taking into
      account several relevant variables such as molecule-ligand distance and the
      energy function, which is essential to understand binding affinities. We put
      emphasis on mapping molecular docking paths obtained from Molecular Dynamics or
      Monte Carlo simulations, and provide time-dependent visualizations for different
      energy components and particle resolutions: atoms, groups or residues. The
      presented visualizations have the potential to support domain experts in a more
      efficient drug or enzyme design process.

PMID- 27875188
TI  - PelVis: Atlas-based Surgical Planning for Oncological Pelvic Surgery.
AB  - Due to the intricate relationship between the pelvic organs and vital structures,
      such as vessels and nerves, pelvic anatomy is often considered to be complex to
      comprehend. In oncological pelvic surgery, a trade-off has to be made between
      complete tumor resection and preserving function by preventing damage to the
      nerves. Damage to the autonomic nerves causes undesirable post-operative side
      effects such as fecal and urinal incontinence, as well as sexual dysfunction in
      up to 80 percent of the cases. Since these autonomic nerves are not visible in
      pre-operative MRI scans or during surgery, avoiding nerve damage during such a
      surgical procedure becomes challenging. In this work, we present visualization
      methods to represent context, target, and risk structures for surgical planning.
      We employ distance-based and occlusion management techniques in an atlas-based
      surgical planning tool for oncological pelvic surgery. Patient-specific pre
      operative MRI scans are registered to an atlas model that includes nerve
      information. Through several interactive linked views, the spatial relationships
      and distances between the organs, tumor and risk zones are visualized to improve
      understanding, while avoiding occlusion. In this way, the surgeon can examine
      surgically relevant structures and plan the procedure before going into the
      operating theater, thus raising awareness of the autonomic nerve zone regions and
      potentially reducing post-operative complications. Furthermore, we present the
      results of a domain expert evaluation with surgical oncologists that demonstrates
      the advantages of our approach.

PMID- 27875189
TI  - Corresponding Supine and Prone Colon Visualization Using Eigenfunction Analysis
      and Fold Modeling.
AB  - We present a method for registration and visualization of corresponding supine
      and prone virtual colonoscopy scans based on eigenfunction analysis and fold
      modeling. In virtual colonoscopy, CT scans are acquired with the patient in two
      positions, and their registration is desirable so that physicians can corroborate
      findings between scans. Our algorithm performs this registration efficiently
      through the use of Fiedler vector representation (the second eigenfunction of the
      Laplace-Beltrami operator). This representation is employed to first perform
      global registration of the two colon positions. The registration is then locally
      refined using the haustral folds, which are automatically segmented using the 3D
      level sets of the Fiedler vector. The use of Fiedler vectors and the segmented
      folds presents a precise way of visualizing corresponding regions across datasets
      and visual modalities. We present multiple methods of visualizing the results,
      including 2D flattened rendering and the corresponding 3D endoluminal views. The
      precise fold modeling is used to automatically find a suitable cut for the 2D
      flattening, which provides a less distorted visualization. Our approach is
      robust, and we demonstrate its efficiency and efficacy by showing matched views
      on both the 2D flattened colons and in the 3D endoluminal view. We analytically
      evaluate the results by measuring the distance between features on the registered
      colons, and we also assess our fold segmentation against 20 manually labeled
      datasets. We have compared our results analytically to previous methods, and have
      found our method to achieve superior results. We also prove the hot spots
      conjecture for modeling cylindrical topology using Fiedler vector representation,
      which allows our approach to be used for general cylindrical geometry modeling
      and feature extraction.

PMID- 27875191
TI  - Visualization as Seen through its Research Paper Keywords.
AB  - We present the results of a comprehensive multi-pass analysis of visualization
      paper keywords supplied by authors for their papers published in the IEEE
      Visualization conference series (now called IEEE VIS) between 1990-2015. From
      this analysis we derived a set of visualization topics that we discuss in the
      context of the current taxonomy that is used to categorize papers and assign
      reviewers in the IEEE VIS reviewing process. We point out missing and
      overemphasized topics in the current taxonomy and start a discussion on the
      importance of establishing common visualization terminology. Our analysis of
      research topics in visualization can, thus, serve as a starting point to (a) help
      create a common vocabulary to improve communication among different visualization
      sub-groups, (b) facilitate the process of understanding differences and
      commonalities of the various research sub-fields in visualization, (c) provide an
      understanding of emerging new research trends, (d) facilitate the crucial step of
      finding the right reviewers for research submissions, and (e) it can eventually
      lead to a comprehensive taxonomy of visualization research. One additional
      tangible outcome of our work is an online query tool (http://keyvis.org/) that
      allows visualization researchers to easily browse the 3952 keywords used for IEEE
      VIS papers since 1990 to find related work or make informed keyword choices.

PMID- 27875190
TI  - Combined Visualization of Vessel Deformation and Hemodynamics in Cerebral
      Aneurysms.
AB  - We present the first visualization tool that combines patient-specific
      hemodynamics with information about the vessel wall deformation and wall
      thickness in cerebral aneurysms. Such aneurysms bear the risk of rupture, whereas
      their treatment also carries considerable risks for the patient. For the patient
      specific rupture risk evaluation and treatment analysis, both morphological and
      hemodynamic data have to be investigated. Medical researchers emphasize the
      importance of analyzing correlations between wall properties such as the wall
      deformation and thickness, and hemodynamic attributes like the Wall Shear Stress
      and near-wall flow. Our method uses a linked 2.5D and 3D depiction of the
      aneurysm together with blood flow information that enables the simultaneous
      exploration of wall characteristics and hemodynamic attributes during the cardiac
      cycle. We thus offer medical researchers an effective visual exploration tool for
      aneurysm treatment risk assessment. The 2.5D view serves as an overview that
      comprises a projection of the vessel surface to a 2D map, providing an occlusion
      free surface visualization combined with a glyph-based depiction of the local
      wall thickness. The 3D view represents the focus upon which the data exploration
      takes place. To support the time-dependent parameter exploration and expert
      collaboration, a camera path is calculated automatically, where the user can
      place landmarks for further exploration of the properties. We developed a GPU
      based implementation of our visualizations with a flexible interactive data
      exploration mechanism. We designed our techniques in collaboration with domain
      experts, and provide details about the evaluation.

PMID- 27875192
TI  - Comparing Cross-Sections and 3D Renderings for Surface Matching Tasks Using
      Physical Ground Truths.
AB  - Within the visualization community there are some well-known techniques for
      visualizing 3D spatial data and some general assumptions about how perception
      affects the performance of these techniques in practice. However, there is a lack
      of empirical research backing up the possible performance differences among the
      basic techniques for general tasks. One such assumption is that 3D renderings are
      better for obtaining an overview, whereas cross sectional visualizations such as
      the commonly used Multi-Planar Reformation (MPR) are better for supporting
      detailed analysis tasks. In the present study we investigated this common
      assumption by examining the difference in performance between MPR and 3D
      rendering for correctly identifying a known surface. We also examined whether
      prior experience working with image data affects the participant's performance,
      and whether there was any difference between interactive or static versions of
      the visualizations. Answering this question is important because it can be used
      as part of a scientific and empirical basis for determining when to use which of
      the two techniques. An advantage of the present study compared to other studies
      is that several factors were taken into account to compare the two techniques.
      The problem was examined through an experiment with 45 participants, where
      physical objects were used as the known surface (ground truth). Our findings
      showed that: 1. The 3D renderings largely outperformed the cross sections; 2.
      Interactive visualizations were partially more effective than static
      visualizations; and 3. The high experience group did not generally outperform the
      low experience group.

PMID- 27875193
TI  - Urban Pulse: Capturing the Rhythm of Cities.
AB  - Cities are inherently dynamic. Interesting patterns of behavior typically
      manifest at several key areas of a city over multiple temporal resolutions.
      Studying these patterns can greatly help a variety of experts ranging from city
      planners and architects to human behavioral experts. Recent technological
      innovations have enabled the collection of enormous amounts of data that can help
      in these studies. However, techniques using these data sets typically focus on
      understanding the data in the context of the city, thus failing to capture the
      dynamic aspects of the city. The goal of this work is to instead understand the
      city in the context of multiple urban data sets. To do so, we define the concept
      of an "urban pulse" which captures the spatio-temporal activity in a city across
      multiple temporal resolutions. The prominent pulses in a city are obtained using
      the topology of the data sets, and are characterized as a set of beats. The beats
      are then used to analyze and compare different pulses. We also design a visual
      exploration framework that allows users to explore the pulses within and across
      multiple cities under different conditions. Finally, we present three case
      studies carried out by experts from two different domains that demonstrate the
      utility of our framework.

PMID- 27875194
TI  - Visualization and Extraction of Carvings for Heritage Conservation.
AB  - We present novel techniques for visualizing, illustrating, analyzing, and
      generating carvings in surfaces. In particular, we consider the carvings in the
      plaster of the cloister of the Magdeburg cathedral, which dates to the 13th
      century. Due to aging and weathering, the carvings have flattened. Historians and
      restorers are highly interested in using digitalization techniques to analyze
      carvings in historic artifacts and monuments and to get impressions and
      illustrations of their original shape and appearance. Moreover, museums and
      churches are interested in such illustrations for presenting them to visitors.
      The techniques that we propose allow for detecting, selecting, and visualizing
      carving structures. In addition, we introduce an example-based method for
      generating carvings. The resulting tool, which integrates all techniques, was
      evaluated by three experienced restorers to assess the usefulness and
      applicability. Furthermore, we compared our approach with exaggerated shading and
      other state-of-the-art methods.

PMID- 27875195
TI  - In Situ Distribution Guided Analysis and Visualization of Transonic Jet Engine
      Simulations.
AB  - Study of flow instability in turbine engine compressors is crucial to understand
      the inception and evolution of engine stall. Aerodynamics experts have been
      working on detecting the early signs of stall in order to devise novel stall
      suppression technologies. A state-of-the-art Navier-Stokes based, time-accurate
      computational fluid dynamics simulator, TURBO, has been developed in NASA to
      enhance the understanding of flow phenomena undergoing rotating stall. Despite
      the proven high modeling accuracy of TURBO, the excessive simulation data
      prohibits post-hoc analysis in both storage and I/O time. To address these issues
      and allow the expert to perform scalable stall analysis, we have designed an in
      situ distribution guided stall analysis technique. Our method summarizes
      statistics of important properties of the simulation data in situ using a
      probabilistic data modeling scheme. This data summarization enables statistical
      anomaly detection for flow instability in post analysis, which reveals the
      spatiotemporal trends of rotating stall for the expert to conceive new
      hypotheses. Furthermore, the verification of the hypotheses and exploratory
      visualization using the summarized data are realized using probabilistic
      visualization techniques such as uncertain isocontouring. Positive feedback from
      the domain scientist has indicated the efficacy of our system in exploratory
      stall analysis.

PMID- 27875197
TI  - Time-Hierarchical Clustering and Visualization of Weather Forecast Ensembles.
AB  - We propose a new approach for analyzing the temporal growth of the uncertainty in
      ensembles of weather forecasts which are started from perturbed but similar
      initial conditions. As an alternative to traditional approaches in meteorology,
      which use juxtaposition and animation of spaghetti plots of iso-contours, we make
      use of contour clustering and provide means to encode forecast dynamics and
      spread in one single visualization. Based on a given ensemble clustering in a
      specified time window, we merge clusters in time-reversed order to indicate when
      and where forecast trajectories start to diverge. We present and compare
      different visualizations of the resulting time-hierarchical grouping, including
      space-time surfaces built by connecting cluster representatives over time, and
      stacked contour variability plots. We demonstrate the effectiveness of our visual
      encodings with forecast examples of the European Centre for Medium-Range Weather
      Forecasts, which convey the evolution of specific features in the data as well as
      the temporally increasing spatial variability.

PMID- 27875196
TI  - Decal-Maps: Real-Time Layering of Decals on Surfaces for Multivariate
      Visualization.
AB  - We introduce the use of decals for multivariate visualization design. Decals are
      visual representations that are used for communication; for example, a pattern, a
      text, a glyph, or a symbol, transferred from a 2D-image to a surface upon
      contact. By creating what we define as decal-maps, we can design a set of images
      or patterns that represent one or more data attributes. We place decals on the
      surface considering the data pertaining to the locations we choose. We propose a
      (texture mapping) local parametrization that allows placing decals on arbitrary
      surfaces interactively, even when dealing with a high number of decals. Moreover,
      we extend the concept of layering to allow the co-visualization of an increased
      number of attributes on arbitrary surfaces. By combining decal-maps, color-maps
      and a layered visualization, we aim to facilitate and encourage the creative
      process of designing multivariate visualizations. Finally, we demonstrate the
      general applicability of our technique by providing examples of its use in a
      variety of contexts.

PMID- 27875198
TI  - Visualization of Time-Varying Weather Ensembles across Multiple Resolutions.
AB  - Uncertainty quantification in climate ensembles is an important topic for the
      domain scientists, especially for decision making in the real-world scenarios.
      With powerful computers, simulations now produce time-varying and multi
      resolution ensemble data sets. It is of extreme importance to understand the
      model sensitivity given the input parameters such that more computation power can
      be allocated to the parameters with higher influence on the output. Also, when
      ensemble data is produced at different resolutions, understanding the accuracy of
      different resolutions helps the total time required to produce a desired quality
      solution with improved storage and computation cost. In this work, we propose to
      tackle these non-trivial problems on the Weather Research and Forecasting (WRF)
      model output. We employ a moment independent sensitivity measure to quantify and
      analyze parameter sensitivity across spatial regions and time domain. A
      comparison of clustering structures across three resolutions enables the users to
      investigate the sensitivity variation over the spatial regions of the five input
      parameters. The temporal trend in the sensitivity values is explored via an MDS
      view linked with a line chart for interactive brushing. The spatial and temporal
      views are connected to provide a full exploration system for complete spatio
      temporal sensitivity analysis. To analyze the accuracy across varying
      resolutions, we formulate a Bayesian approach to identify which regions are
      better predicted at which resolutions compared to the observed precipitation.
      This information is aggregated over the time domain and finally encoded in an
      output image through a custom color map that guides the domain experts towards an
      adaptive grid implementation given a cost model. Users can select and further
      analyze the spatial and temporal error patterns for multi-resolution accuracy
      analysis via brushing and linking on the produced image. In this work, we
      collaborate with a domain expert whose feedback shows the effectiveness of our
      proposed exploration work-flow.

PMID- 27875199
TI  - A Fractional Cartesian Composition Model for Semi-Spatial Comparative
      Visualization Design.
AB  - The study of spatial data ensembles leads to substantial visualization challenges
      in a variety of applications. In this paper, we present a model for comparative
      visualization that supports the design of according ensemble visualization
      solutions by partial automation. We focus on applications, where the user is
      interested in preserving selected spatial data characteristics of the data as
      much as possible-even when many ensemble members should be jointly studied using
      comparative visualization. In our model, we separate the design challenge into a
      minimal set of user-specified parameters and an optimization component for the
      automatic configuration of the remaining design variables. We provide an
      illustrated formal description of our model and exemplify our approach in the
      context of several application examples from different domains in order to
      demonstrate its generality within the class of comparative visualization problems
      for spatial data ensembles.

PMID- 27875200
TI  - Vol2velle: Printable Interactive Volume Visualization.
AB  - Interaction is an indispensable aspect of data visualization. The presentation of
      volumetric data, in particular, often significantly benefits from interactive
      manipulation of parameters such as transfer functions, rendering styles, or
      clipping planes. However, when we want to create hardcopies of such
      visualizations, this essential aspect is lost. In this paper, we present a novel
      approach for creating hardcopies of volume visualizations which preserves a
      certain degree of interactivity. We present a method for automatically generating
      Volvelles, printable tangible wheel charts that can be manipulated to explore
      different parameter settings. Our interactive system allows the flexible mapping
      of arbitrary visualization parameters and supports advanced features such as
      linked views. The resulting designs can be easily reproduced using a standard
      printer and assembled within a few minutes.

PMID- 27875201
TI  - Categorical Colormap Optimization with Visualization Case Studies.
AB  - Mapping a set of categorical values to different colors is an elementary
      technique in data visualization. Users of visualization software routinely rely
      on the default colormaps provided by a system, or colormaps suggested by software
      such as ColorBrewer. In practice, users often have to select a set of colors in a
      semantically meaningful way (e.g., based on conventions, color metaphors, and
      logological associations), and consequently would like to ensure their perceptual
      differentiation is optimized. In this paper, we present an algorithmic approach
      for maximizing the perceptual distances among a set of given colors. We address
      two technical problems in optimization, i.e., (i) the phenomena of local maxima
      that halt the optimization too soon, and (ii) the arbitrary reassignment of
      colors that leads to the loss of the original semantic association. We paid
      particular attention to different types of constraints that users may wish to
      impose during the optimization process. To demonstrate the effectiveness of this
      work, we tested this technique in two case studies. To reach out to a wider range
      of users, we also developed a web application called Colourmap Hospital.

PMID- 27875202
TI  - Hybrid Tactile/Tangible Interaction for 3D Data Exploration.
AB  - We present the design and evaluation of an interface that combines tactile and
      tangible paradigms for 3D visualization. While studies have demonstrated that
      both tactile and tangible input can be efficient for a subset of 3D manipulation
      tasks, we reflect here on the possibility to combine the two complementary input
      types. Based on a field study and follow-up interviews, we present a conceptual
      framework of the use of these different interaction modalities for visualization
      both separately and combined-focusing on free exploration as well as precise
      control. We present a prototypical application of a subset of these combined
      mappings for fluid dynamics data visualization using a portable, position-aware
      device which offers both tactile input and tangible sensing. We evaluate our
      approach with domain experts and report on their qualitative feedback.

PMID- 27875203
TI  - GlyphLens: View-Dependent Occlusion Management in the Interactive Glyph
      Visualization.
AB  - Glyph as a powerful multivariate visualization technique is used to visualize
      data through its visual channels. To visualize 3D volumetric dataset, glyphs are
      usually placed on 2D surface, such as the slicing plane or the feature surface,
      to avoid occluding each other. However, the 3D spatial structure of some features
      may be missing. On the other hand, placing large number of glyphs over the entire
      3D space results in occlusion and visual clutter that make the visualization
      ineffective. To avoid the occlusion, we propose a view-dependent interactive 3D
      lens that removes the occluding glyphs by pulling the glyphs aside through the
      animation. We provide two space deformation models and two lens shape models to
      displace the glyphs based on their spatial distributions. After the displacement,
      the glyphs around the user-interested region are still visible as the context
      information, and their spatial structures are preserved. Besides, we attenuate
      the brightness of the glyphs inside the lens based on their depths to provide
      more depth cue. Furthermore, we developed an interactive glyph visualization
      system to explore different glyph-based visualization applications. In the
      system, we provide a few lens utilities that allows users to pick a glyph or a
      feature and look at it from different view directions. We compare different
      display/interaction techniques to visualize/manipulate our lens and glyphs.

PMID- 27875204
TI  - A Versatile and Efficient GPU Data Structure for Spatial Indexing.
AB  - In this paper we present a novel GPU-based data structure for spatial indexing.
      Based on Fenwick trees-a special type of binary indexed trees-our data structure
      allows construction in linear time. Updates and prefixes can be computed in
      logarithmic time, whereas point queries require only constant time on average.
      Unlike competing data structures such as summed-area tables and spatial hashing,
      our data structure requires a constant amount of bits for each data element, and
      it offers unconstrained point queries. This property makes our data structure
      ideally suited for applications requiring unconstrained indexing of large data,
      such as block-storage of large and block-sparse volumes. Finally, we provide
      asymptotic bounds on both run-time and memory requirements, and we show
      applications for which our new data structure is useful.

PMID- 27875205
TI  - Progressive Direct Volume-to-Volume Transformation.
AB  - We present a novel technique to generate transformations between arbitrary
      volumes, providing both expressive distances and smooth interpolates. In contrast
      to conventional morphing or warping approaches, our technique requires no user
      guidance, intermediate representations (like extracted features), or blending,
      and imposes no restrictions regarding shape or structure. Our technique operates
      directly on the volumetric data representation, and while linear programming
      approaches could solve the underlying problem optimally, their polynomial
      complexity makes them infeasible for high-resolution volumes. We therefore
      propose a progressive refinement approach designed for parallel execution that is
      able to quickly deliver approximate results that are iteratively improved toward
      the optimum. On this basis, we further present a new approach for the streaming
      selection of time steps in temporal data that allows for the reconstruction of
      the full sequence with a user-specified error bound. We finally demonstrate the
      utility of our technique for different applications, compare our approach against
      alternatives, and evaluate its characteristics with a variety of different data
      sets.

PMID- 27875206
TI  - OSPRay - A CPU Ray Tracing Framework for Scientific Visualization.
AB  - Scientific data is continually increasing in complexity, variety and size, making
      efficient visualization and specifically rendering an ongoing challenge.
      Traditional rasterization-based visualization approaches encounter performance
      and quality limitations, particularly in HPC environments without dedicated
      rendering hardware. In this paper, we present OSPRay, a turn-key CPU ray tracing
      framework oriented towards production-use scientific visualization which can
      utilize varying SIMD widths and multiple device backends found across diverse HPC
      resources. This framework provides a high-quality, efficient CPU-based solution
      for typical visualization workloads, which has already been integrated into
      several prevalent visualization packages. We show that this system delivers the
      performance, high-level API simplicity, and modular device support needed to
      provide a compelling new rendering framework for implementing efficient
      scientific visualization workflows.

PMID- 27875207
TI  - Direct Multifield Volume Ray Casting of Fiber Surfaces.
AB  - Multifield data are common in visualization. However, reducing these data to
      comprehensible geometry is a challenging problem. Fiber surfaces, an analogy of
      isosurfaces to bivariate volume data, are a promising new mechanism for
      understanding multifield volumes. In this work, we explore direct ray casting of
      fiber surfaces from volume data without any explicit geometry extraction. We
      sample directly along rays in domain space, and perform geometric tests in range
      space where fibers are defined, using a signed distance field derived from the
      control polygons. Our method requires little preprocess, and enables real-time
      exploration of data, dynamic modification and pixel-exact rendering of fiber
      surfaces, and support for higher-order interpolation in domain space. We
      demonstrate this approach on several bivariate datasets, including analysis of
      multi-field combustion data.

PMID- 27875209
TI  - Jacobi Fiber Surfaces for Bivariate Reeb Space Computation.
AB  - This paper presents an efficient algorithm for the computation of the Reeb space
      of an input bivariate piecewise linear scalar function f defined on a tetrahedral
      mesh. By extending and generalizing algorithmic concepts from the univariate case
      to the bivariate one, we report the first practical, output-sensitive algorithm
      for the exact computation of such a Reeb space. The algorithm starts by
      identifying the Jacobi set of f, the bivariate analogs of critical points in the
      univariate case. Next, the Reeb space is computed by segmenting the input mesh
      along the new notion of Jacobi Fiber Surfaces, the bivariate analog of critical
      contours in the univariate case. We additionally present a simplification
      heuristic that enables the progressive coarsening of the Reeb space. Our
      algorithm is simple to implement and most of its computations can be trivially
      parallelized. We report performance numbers demonstrating orders of magnitude
      speedups over previous approaches, enabling for the first time the tractable
      computation of bivariate Reeb spaces in practice. Moreover, unlike range-based
      quantization approaches (such as the Joint Contour Net), our algorithm is
      parameter-free. We demonstrate the utility of our approach by using the Reeb
      space as a semi-automatic segmentation tool for bivariate data. In particular, we
      introduce continuous scatterplot peeling, a technique which enables the reduction
      of the cluttering in the continuous scatterplot, by interactively selecting the
      features of the Reeb space to project. We provide a VTK-based C++ implementation
      of our algorithm that can be used for reproduction purposes or for the
      development of new Reeb space based visualization techniques.

PMID- 27875208
TI  - Topological Analysis of Inertial Dynamics.
AB  - Traditional vector field visualization has a close focus on velocity, and is
      typically constrained to the dynamics of massless particles. In this paper, we
      present a novel approach to the analysis of the force-induced dynamics of
      inertial particles. These forces can arise from acceleration fields such as
      gravitation, but also be dependent on the particle dynamics itself, as in the
      case of magnetism. Compared to massless particles, the velocity of an inertial
      particle is not determined solely by its position and time in a vector field. In
      contrast, its initial velocity can be arbitrary and impacts the dynamics over its
      entire lifetime. This leads to a four-dimensional problem for 2D setups, and a
      six-dimensional problem for the 3D case. Our approach avoids this increase in
      dimensionality and tackles the visualization by an integrated topological
      analysis approach. We demonstrate the utility of our approach using a synthetic
      time-dependent acceleration field, a system of magnetic dipoles, and N-body
      systems both in 2D and 3D.

PMID- 27875210
TI  - Backward Finite-Time Lyapunov Exponents in Inertial Flows.
AB  - Inertial particles are finite-sized objects that are carried by fluid flows and
      in contrast to massless tracer particles they are subject to inertia effects. In
      unsteady flows, the dynamics of tracer particles have been extensively studied by
      the extraction of Lagrangian coherent structures (LCS), such as hyperbolic LCS as
      ridges of the Finite-Time Lyapunov Exponent (FTLE). The extension of the rich LCS
      framework to inertial particles is currently a hot topic in the CFD literature
      and is actively under research. Recently, backward FTLE on tracer particles has
      been shown to correlate with the preferential particle settling of small inertial
      particles. For larger particles, inertial trajectories may deviate strongly from
      (massless) tracer trajectories, and thus for a better agreement, backward FTLE
      should be computed on inertial trajectories directly. Inertial backward
      integration, however, has not been possible until the recent introduction of the
      influence curve concept, which - given an observation and an initial velocity -
      allows to recover all sources of inertial particles as tangent curves of a
      derived vector field. In this paper, we show that FTLE on the influence curve
      vector field is in agreement with preferential particle settling and more
      importantly it is not only valid for small (near-tracer) particles. We further
      generalize the influence curve concept to general equations of motion in unsteady
      spatio-velocity phase spaces, which enables backward integration with more
      general equations of motion. Applying the influence curve concept to tracer
      particles in the spatio-velocity domain emits streaklines in massless flows as
      tangent curves of the influence curve vector field. We demonstrate the
      correlation between inertial backward FTLE and the preferential particle settling
      in a number of unsteady vector fields.

PMID- 27875211
TI  - Glyphs for General Second-Order 2D and 3D Tensors.
AB  - Glyphs are a powerful tool for visualizing second-order tensors in a variety of
      scientic data as they allow to encode physical behavior in geometric properties.
      Most existing techniques focus on symmetric tensors and exclude non-symmetric
      tensors where the eigenvectors can be non-orthogonal or complex. We present a new
      construction of 2d and 3d tensor glyphs based on piecewise rational curves and
      surfaces with the following properties: invariance to (a) isometries and (b)
      scaling, (c) direct encoding of all real eigenvalues and eigenvectors, (d) one-to
      one relation between the tensors and glyphs, (e) glyph continuity under changing
      the tensor. We apply the glyphs to visualize the Jacobian matrix fields of a
      number of 2d and 3d vector fields.

PMID- 27875212
TI  - Hairy Slices: Evaluating the Perceptual Effectiveness of Cutting Plane Glyphs for
      3D Vector Fields.
AB  - Three-dimensional vector fields are common datasets throughout the sciences.
      Visualizing these fields is inherently difficult due to issues such as visual
      clutter and self-occlusion. Cutting planes are often used to overcome these
      issues by presenting more manageable slices of data. The existing literature
      provides many techniques for visualizing the flow through these cutting planes;
      however, there is a lack of empirical studies focused on the underlying
      perceptual cues that make popular techniques successful. This paper presents a
      quantitative human factors study that evaluates static monoscopic depth and
      orientation cues in the context of cutting plane glyph designs for exploring and
      analyzing 3D flow fields. The goal of the study was to ascertain the relative
      effectiveness of various techniques for portraying the direction of flow through
      a cutting plane at a given point, and to identify the visual cues and
      combinations of cues involved, and how they contribute to accurate performance.
      It was found that increasing the dimensionality of line-based glyphs into tubular
      structures enhances their ability to convey orientation through shading, and that
      increasing their diameter intensifies this effect. These tube-based glyphs were
      also less sensitive to visual clutter issues at higher densities. Adding shadows
      to lines was also found to increase perception of flow direction. Implications of
      the experimental results are discussed and extrapolated into a number of
      guidelines for designing more perceptually effective glyphs for 3D vector field
      visualizations.

PMID- 27875214
TI  - Visual Vibrometry: Estimating Material Properties from Small Motions in Video.
AB  - The estimation of material properties is important for scene understanding, with
      many applications in vision, robotics, and structural engineering. This paper
      connects fundamentals of vibration mechanics with computer vision techniques in
      order to infer material properties from small, often imperceptible motions in
      video. Objects tend to vibrate in a set of preferred modes. The frequencies of
      these modes depend on the structure and material properties of an object. We show
      that by extracting these frequencies from video of a vibrating object, we can
      often make inferences about that object's material properties. We demonstrate our
      approach by estimating material properties for a variety of objects by observing
      their motion in high-speed and regular frame rate video.

PMID- 27875213
TI  - On the Latent Variable Interpretation in Sum-Product Networks.
AB  - One of the central themes in Sum-Product networks (SPNs) is the interpretation of
      sum nodes as marginalized latent variables (LVs). This interpretation yields an
      increased syntactic or semantic structure, allows the application of the EM
      algorithm and to efficiently perform MPE inference. In literature, the LV
      interpretation was justified by explicitly introducing the indicator variables
      corresponding to the LVs' states. However, as pointed out in this paper, this
      approach is in conflict with the completeness condition in SPNs and does not
      fully specify the probabilistic model. We propose a remedy for this problem by
      modifying the original approach for introducing the LVs, which we call SPN
      augmentation. We discuss conditional independencies in augmented SPNs, formally
      establish the probabilistic interpretation of the sum-weights and give an
      interpretation of augmented SPNs as Bayesian networks. Based on these results, we
      find a sound derivation of the EM algorithm for SPNs. Furthermore, the Viterbi
      style algorithm for MPE proposed in literature was never proven to be correct. We
      show that this is indeed a correct algorithm, when applied to selective SPNs, and
      in particular when applied to augmented SPNs. Our theoretical results are
      confirmed in experiments on synthetic data and 103 real-world datasets.

PMID- 27875215
TI  - Local Submodularization for Binary Pairwise Energies.
AB  - Many computer vision problems require optimization of binary non-submodular
      energies. We propose a general optimization framework based on local submodular
      approximations (LSA). Unlike standard LP relaxation methods that linearize the
      whole energy globally, our approach iteratively approximates the energy locally.
      On the other hand, unlike standard local optimization methods (e.g., gradient
      descent or projection techniques) we use non-linear submodular approximations and
      optimize them without leaving the domain of integer solutions. We discuss two
      specific LSA algorithms based on trust region and auxiliary function principles,
      LSA-TR and LSA-AUX. The proposed methods obtain state-of-the-art results on a
      wide range of applications such as binary deconvolution, curvature
      regularization, inpainting, segmentation with repulsion and two types of shape
      priors. Finally, we discuss a move-making extension to the LSA-TR approach. While
      our paper is focused on pairwise energies, our ideas extend to higher-order
      problems. The code is available online.

PMID- 27875216
TI  - Image Registration and Change Detection under Rolling Shutter Motion Blur.
AB  - In this paper, we address the problem of registering a distorted image and a
      reference image of the same scene by estimating the camera motion that had caused
      the distortion. We simultaneously detect the regions of changes between the two
      images. We attend to the coalesced effect of rolling shutter and motion blur that
      occurs frequently in moving CMOS cameras. We first model a general image
      formation framework for a 3D scene following a layered approach in the presence
      of rolling shutter and motion blur. We then develop an algorithm which performs
      layered registration to detect changes. This algorithm includes an optimisation
      problem that leverages the sparsity of the camera trajectory in the pose space
      and the sparsity of changes in the spatial domain. We create a synthetic dataset
      for change detection in the presence of motion blur and rolling shutter effect
      covering different types of camera motion for both planar and 3D scenes. We
      compare our method with existing registration methods and also show several real
      examples captured with CMOS cameras.

PMID- 27875219
TI  - Automatic Tracking and Motility Analysis of Human Sperm in Time-Lapse Images.
AB  - We present a fully automated multi-sperm tracking algorithm. It has the
      demonstrated capability to detect and track simultaneously hundreds of sperm
      cells in recorded videos while accurately measuring motility parameters over time
      and with minimal operator intervention. Algorithms of this kind may help in
      associating dynamic swimming parameters of human sperm cells with fertility and
      fertilization rates. Specifically, we offer an image processing method, based on
      radar tracking algorithms, that detects and tracks automatically the swimming
      paths of human sperm cells in timelapse microscopy image sequences of the kind
      that is analyzed by fertility clinics. Adapting the well-known joint
      probabilistic data association filter (JPDAF), we automatically tracked hundreds
      of human sperm simultaneously and measured their dynamic swimming parameters over
      time. Unlike existing CASA instruments, our algorithm has the capability to track
      sperm swimming in close proximity to each other and during apparent cell-to-cell
      collisions. Collecting continuously parameters for each sperm tracked without
      sample dilution (currently impossible using standard CASA systems) provides an
      opportunity to compare such data with standard fertility rates. The use of our
      algorithm thus has the potential to free the clinician from having to rely on
      elaborate motility measurements obtained manually by technicians, speed up semen
      processing, and provide medical practitioners and researchers with more useful
      data than are currently available.

PMID- 27875220
TI  - High-Quality-Factor and Low-Temperature-Dependence SMR FBAR Based on BST Using
      MOD Method.
AB  - This paper presents the design, fabrication, and experimental evaluation of
      switchable and tunable thin-film bulk acoustic wave (BAW) resonators and filters
      with metal-organic solution deposited barium strontium titanate (BST) for radio
      frequency (RF) applications. The switchability and tunability of these devices
      come from utilizing the electrostrictive effect of ferroelectric materials such
      as BST with the application of an external dc bias voltage. The BAW resonators
      and filters in this paper were fabricated on a high-resistivity silicon substrate
      as a solidly mounted resonator structure with eight layers of silicon dioxide and
      tantalum pentoxide as a Bragg reflector. A 170-nm BST thin-film thickness with
      Br/Sr (70/30) composition was deposited using the metal-organic deposition
      solution chemical technique. The measurements of the RF transmission
      characteristics showed no resonance (OFF state) with zero bias voltage across the
      terminals of the resonator. At nonzero applied bias, a switching response (ON
      state) was observed at near 5.44 GHz. With the increasing magnitude of the
      applied bias across the film, the resonance increased in intensity by showing a
      quality factor of 746 and shifted to a lower frequency of 5.375 GHz with a
      tunability of 1.3%. The temperature dependence of the fabricated device was
      measured from room temperature up to 80  degrees C and showed a temperature
      coefficient of frequency of -12.595 ppm/ degrees C.

PMID- 27875221
TI  - A Context-Driven Extractive Framework for Generating Realistic Image
      Descriptions.
AB  - Automatic image annotation methods are extremely beneficial for image search,
      retrieval, and organization systems. The lack of strict correlation between
      semantic concepts and visual features, referred to as the semantic gap, is a huge
      challenge for annotation systems. In this paper, we propose an image annotation
      model that incorporates contextual cues collected from sources both intrinsic and
      extrinsic to images, to bridge the semantic gap. The main focus of this paper is
      a large real-world data set of news images that we collected. Unlike standard
      image annotation benchmark data sets, our data set does not require human
      annotators to generate artificial ground truth descriptions after data
      collection, since our images already include contextually meaningful and real
      world captions written by journalists. We thoroughly study the nature of image
      descriptions in this real-world data set. News image captions describe both
      visual contents and the contexts of images. Auxiliary information sources are
      also available with such images in the form of news article and metadata (e.g.,
      keywords and categories). The proposed framework extracts contextual-cues from
      available sources of different data modalities and transforms them into a common
      representation space, i.e., the probability space. Predicted annotations are
      later transformed into sentence-like captions through an extractive framework
      applied over news articles. Our context-driven framework outperforms the state of
      the art on the collected data set of approximately 20 000 items, as well as on a
      previously available smaller news images data set.

PMID- 27875223
TI  - A Joint Compression Scheme of Video Feature Descriptors and Visual Content.
AB  - High-efficiency compression of visual feature descriptors has recently emerged as
      an active topic due to the rapidly increasing demand in mobile visual retrieval
      over bandwidth-limited networks. However, transmitting only those feature
      descriptors may largely restrict its application scale due to the lack of
      necessary visual content. To facilitate the wide spread of feature descriptors, a
      hybrid framework of jointly compressing the feature descriptors and visual
      content is highly desirable. In this paper, such a content-plus-feature coding
      scheme is investigated, aiming to shape the next generation of video compression
      system toward visual retrieval, where the high-efficiency coding of both feature
      descriptors and visual content can be achieved by exploiting the interactions
      between each other. On the one hand, visual feature descriptors can achieve
      compact and efficient representation by taking advantages of the structure and
      motion information in the compressed video stream. To optimize the retrieval
      performance, a novel rate-accuracy optimization technique is proposed to
      accurately estimate the retrieval performance degradation in feature coding. On
      the other hand, the already compressed feature data can be utilized to further
      improve the video coding efficiency by applying feature matching-based affine
      motion compensation. Extensive simulations have shown that the proposed joint
      compression framework can offer significant bitrate reduction in representing
      both feature descriptors and video frames, while simultaneously maintaining the
      state-of-the-art visual retrieval performance.

PMID- 27875224
TI  - A Parallel Proximal Algorithm for Anisotropic Total Variation Minimization.
AB  - Total variation (TV) is a one of the most popular regularizers for stabilizing
      the solution of ill-posed inverse problems. This paper proposes a novel proximal
      gradient algorithm for minimizing TV regularized least-squares cost functionals.
      Unlike traditional methods that require nested iterations for computing the
      proximal step of TV, our algorithm approximates the latter with several simple
      proximals that have closed form solutions. We theoretically prove that the
      proposed parallel proximal method achieves the TV solution with arbitrarily high
      precision at a global rate of converge that is equivalent to the fast proximal
      gradient methods. The results in this paper have the potential to enhance the
      applicability of TV for solving very large-scale imaging inverse problems.

PMID- 27875225
TI  - The Shape Interaction Matrix-Based Affine Invariant Mismatch Removal for Partial
      Duplicate Image Search.
AB  - Mismatch removal is a key step in many computer vision problems. In this paper,
      we handle the mismatch removal problem by adopting shape interaction matrix
      (SIM). Given the homogeneous coordinates of the two corresponding point sets, we
      first compute the SIMs of the two point sets. Then, we detect the mismatches by
      picking out the most different entries between the two SIMs. Even under strong
      affine transformations, outliers, noises, and burstiness, our method can still
      work well. Actually, this paper is the first non-iterative mismatch removal
      method that achieves affine invariance. Extensive results on synthetic 2D points
      matching data sets and real image matching data sets verify the effectiveness,
      efficiency, and robustness of our method in removing mismatches. Moreover, when
      applied to partial-duplicate image search, our method reaches higher retrieval
      precisions with shorter time cost compared with the state-of-the-art geometric
      verification methods.

PMID- 27875229
TI  - Rapid Detection of Protein Kinase on Capacitive Sensing Platforms.
AB  - In this study, we developed a capacitive sensor for the one-step and label-free
      detection of protein kinase A (PKA) enzyme. Metal-insulator-semiconductor (MIS)
      and electrolyte-insulator-semiconductor (EIS) are a simple electronic transducer,
      which allows efficient detection of the target analyte. For this reason, we
      performed a comparative sensing of PKA on the MIS and EIS capacitive sensor. The
      PKA-specific aptamer was used for the one-step detection. For the immobilization
      of thiolated aptamer, the MIS sensor contained a thin gold layer, whereas the EIS
      sensor had a self-aligned monolayer of gold nanoparticles. The interaction of
      aptamer and PKA changed the charge and density of the sensor surface. The
      quantitative detection of PKA was performed by analyzing the capacitance-voltage
      curve after the aptamer-PKA interaction. The MIS and EIS sensor showed a
      detection limit of 5 U/mL and 1 U/mL, respectively, for the detection of PKA.
      This study suggests valuable sensing platforms for the rapid and sensitive
      biochemical diagnosis.

PMID- 27875231
TI  - eShiver: Lateral Force Feedback on Fingertips through Oscillatory Motion of an
      Electroadhesive Surface.
AB  - We describe a new haptic force feedback device capable of creating lateral shear
      force on a bare fingertip-the eShiver. The eShiver creates a net lateral force
      from in-plane oscillatory motion of a surface synchronized with a "friction
      switch" based on Johnsen-Rahbek electroadhesion. Using an artificial finger, a
      maximum net lateral force of +/-300 mN is achieved at 55 Hz lateral oscillation
      frequency, and net force is shown to be a function of velocity and applied
      voltage, as well as the phase between them. A second set of experiments is
      carried out on a human finger, and a lateral force of up to +/-450 mN is achieved
      at a lateral oscillation frequency of 1,000 Hz. This force is reached at a peak
      lateral surface velocity of 400 mm/s and a peak applied voltage of 400 V. We
      develop a simple lumped parameter model of the eShiver, and a time domain
      simulation of the artificial finger is shown to agree with the experimental
      results. Three distinct zones of operation are found, which predict the
      limitations of force generation and which may be used for optimization. The human
      finger is found to be similar to the artificial finger in its dependence on
      actuation parameters, suggesting that the same lumped parameter model may be
      applied, albeit with different parameters. Curiously, the friction force due to
      Johnsen-Rahbek electroadhesion is found to increase substantially over time as
      the finger remains in contact with the surface. Considerations for optimizing the
      performance of the eShiver are discussed.

PMID- 27875232
TI  - A Novel Algorithm for Learning Sparse Spatio-Spectral Patterns for Event-Related
      Potentials.
AB  - Recent years have witnessed brain-computer interface (BCI) as a promising
      technology for integrating human intelligence and machine intelligence.
      Currently, event-related potential (ERP)-based BCI is an important branch of
      noninvasive electroencephalogram (EEG)-based BCIs. Extracting ERPs from a limited
      number of trials remains challenging due to their low signal-to-noise ratio (SNR)
      and low spatial resolution caused by volume conduction. In this paper, we propose
      a probabilistic model for trial-by-trial concatenated EEG, in which the
      concatenated ERPs are expressed as a linear combination of a set of discrete sine
      and cosine bases. The bases are simply determined by the data length of a single
      trial. A sparse prior on the rank of the spatio-spectral pattern matrix is
      introduced into the model to allow the number of components to be automatically
      determined. A maximum posterior estimation algorithm based on cyclic descent is
      then developed to estimate the spatiospectral patterns. A spatial filter can then
      be obtained by maximizing the SNR of the ERP components. Experiments on both
      synthetic data and real N170 ERP from 13 subjects were conducted to test the
      efficacy and efficiency of the algorithm. The results showed that the proposed
      algorithm can estimate the ERPs more accurately than the several state-of-the-art
      algorithms.

PMID- 27875233
TI  - Multisynchronization of Coupled Heterogeneous Genetic Oscillator Networks via
      Partial Impulsive Control.
AB  - This paper focuses on the collective dynamics of multisynchronization among
      heterogeneous genetic oscillators under a partial impulsive control strategy. The
      coupled nonidentical genetic oscillators are modeled by differential equations
      with uncertainties. The definition of multisynchronization is proposed to
      describe some more general synchronization behaviors in the real. Considering
      that each genetic oscillator consists of a large number of biochemical molecules,
      we design a more manageable impulsive strategy for dynamic networks to achieve
      multisynchronization. Not all the molecules but only a small fraction of them in
      each genetic oscillator are controlled at each impulsive instant. Theoretical
      analysis of multisynchronization is carried out by the control theory approach,
      and a sufficient condition of partial impulsive controller for
      multisynchronization with given error bounds is established. At last, numerical
      simulations are exploited to demonstrate the effectiveness of our results.

PMID- 27875235
TI  - Concept Factorization With Adaptive Neighbors for Document Clustering.
AB  - In this paper, a novel concept factorization (CF) method, called CF with adaptive
      neighbors (CFANs), is proposed. The idea of CFAN is to integrate an ANs
      regularization constraint into the CF decomposition. The goal of CFAN is to
      extract the representation space that maintains geometrical neighborhood
      structure of the data. Similar to the existing graph-regularized CF, CFAN builds
      a neighbor graph weights matrix. The key difference is that the CFAN performs
      dimensionality reduction and finds the neighbor graph weights matrix
      simultaneously. An efficient algorithm is also derived to solve the proposed
      problem. We apply the proposed method to the problem of document clustering on
      the 20 Newsgroups, Reuters-21578, and TDT2 document data sets. Our experiments
      demonstrate the effectiveness of the method.

PMID- 27875236
TI  - Correlation-Based Tracking of Multiple Targets With Hierarchical Layered
      Structure.
AB  - Visual target tracking is one of the most important research areas in the field
      of computer vision. Within this realm, multiple targets tracking (MTT) under
      complicated scene stands out for its great availability in real life
      applications, such as urban traffic surveillance and sports video analysis.
      However, in MTT, main difficulties arise from large variation in target saliency
      and significant motion heterogeneity, which may result in the failure of tracking
      weak targets. To tackle this challenge, a novel hierarchical layered tracking
      structure is proposed to perform tracking sequentially layer-by-layer. Upon this
      layered structure, we establish an intertarget mutual assistance mechanism on
      basis of intertarget correlation exploited among targets. The tracking results of
      a subset of targets can be utilized as additional prior information for tracking
      other targets. Specifically, a nonlinear motion model as well as a target
      interaction model basing on the intertarget correlation are proposed to
      effectively estimate the possible target region-of-interest to facilitate the
      prediction-based tracking. Moreover, the concept of motion entropy is introduced
      to quantitatively measure the degree of motion heterogeneity within the tracking
      scene for layer construction. Compared to other existing methods, extensive
      experiments demonstrated that the proposed method is capable of achieving higher
      tracking performance in complicated scenes, where targets are characterized with
      great heterogeneity.

PMID- 27875237
TI  - Automatic Facial Expression Recognition System Using Deep Network-Based Data
      Fusion.
AB  - This paper presents a novel automatic facial expressions recognition system
      (AFERS) using the deep network framework. The proposed AFERS consists of four
      steps: 1) geometric features extraction; 2) regional local binary pattern (LBP)
      features extraction; 3) fusion of both the features using autoencoders; and 4)
      classification using Kohonen self-organizing map (SOM)-based classifier. This
      paper makes three distinct contributions. The proposed deep network consisting of
      autoencoders and the SOM-based classifier is computationally more efficient and
      performance wise more accurate. The fusion of geometric features with LBP
      features using autoencoders provides better representation of facial expression.
      The SOM-based classifier proposed in this paper has been improved by making use
      of a soft-threshold logic and a better learning algorithm. The performance of the
      proposed approach is validated on two widely used databases (DBs): 1) MMI and 2)
      extended Cohn-Kanade (CK+). An average recognition accuracy of 97.55% in MMI DB
      and 98.95% in CK+ DB are obtained using the proposed algorithm. The recognition
      results obtained from fused features are found to be distinctly superior to both
      recognition using individual features as well as recognition with a direct
      concatenation of the individual feature vectors. Simulation results validate that
      the proposed AFERS is more efficient as compared to the existing approaches.

PMID- 27875238
TI  - Geometric Hypergraph Learning for Visual Tracking.
AB  - Graph-based representation is widely used in visual tracking field by finding
      correct correspondences between target parts in different frames. However, most
      graph-based trackers consider pairwise geometric relations between local parts.
      They do not make full use of the target's intrinsic structure, thereby making the
      representation easily disturbed by errors in pairwise affinities when large
      deformation or occlusion occurs. In this paper, we propose a geometric hypergraph
      learning-based tracking method, which fully exploits high-order geometric
      relations among multiple correspondences of parts in different frames. Then
      visual tracking is formulated as the mode-seeking problem on the hypergraph in
      which vertices represent correspondence hypotheses and hyperedges describe high
      order geometric relations among correspondences. Besides, a confidence-aware
      sampling method is developed to select representative vertices and hyperedges to
      construct the geometric hypergraph for more robustness and scalability. The
      experiments are carried out on three challenging datasets (VOT2014, OTB100, and
      Deform-SOT) to demonstrate that our method performs favorably against other
      existing trackers.

PMID- 27875239
TI  - Semisupervised Prior Free Rare Category Detection With Mixed Criteria.
AB  - Rare category detection aims to find interesting and statistically significant
      anomalies and incorporates ideas from active learning and semisupervised
      learning. The challenge of rare category detection is to find the rare classes of
      the anomalies in a data set where the data distribution is skewed. Most existing
      rare category detection methods suppose that the user knows the specific number
      of all classes in advance, which cannot be satisfied in most real scenarios. In
      this paper, we propose a new rare category detection framework composed of active
      learning and semisupervised hierarchical density-based clustering. The advantage
      of our method is that it is prior free and can benefit the rare category
      detecting process with the labeled data. In addition, the proposed framework can
      handle tasks with nonlinear mappings, which increases the ability to find rare
      classes when the class boundary is sophisticated. Compared to existing methods,
      better results are achieved by our method on both real and synthetic data sets in
      the experiment.

PMID- 27875240
TI  - Distributed Jointly Sparse Multitask Learning Over Networks.
AB  - Distributed data processing over networks has received a lot of attention due to
      its wide applicability. In this paper, we consider the multitask problem of in
      network distributed estimation. For the multitask problem, the unknown parameter
      vectors (tasks) for different nodes can be different. Moreover, considering some
      real application scenarios, it is also assumed that there are some similarities
      among the tasks. Thus, the intertask cooperation is helpful to enhance the
      estimation performance. In this paper, we exploit an additional special
      characteristic of the vectors of interest, namely, joint sparsity, aiming to
      further enhance the estimation performance. A distributed jointly sparse
      multitask algorithm for the collaborative sparse estimation problem is derived.
      In addition, an adaptive intertask cooperation strategy is adopted to improve the
      robustness against the degree of difference among the tasks. The performance of
      the proposed algorithm is analyzed theoretically, and its effectiveness is
      verified by some simulations.

PMID- 27875241
TI  - Dynamical compensation in physiological circuits.
AB  - Biological systems can maintain constant steady-state output despite variation in
      biochemical parameters, a property known as exact adaptation. Exact adaptation is
      achieved using integral feedback, an engineering strategy that ensures that the
      output of a system robustly tracks its desired value. However, it is unclear how
      physiological circuits also keep their output dynamics precise-including the
      amplitude and response time to a changing input. Such robustness is crucial for
      endocrine and neuronal homeostatic circuits because they need to provide a
      precise dynamic response in the face of wide variation in the physiological
      parameters of their target tissues; how such circuits compensate their dynamics
      for unavoidable natural fluctuations in parameters is unknown. Here, we present a
      design principle that provides the desired robustness, which we call dynamical
      compensation (DC). We present a class of circuits that show DC by means of a
      nonlinear feedback loop in which the regulated variable controls the functional
      mass of the controlling endocrine or neuronal tissue. This mechanism applies to
      the control of blood glucose by insulin and explains several experimental
      observations on insulin resistance. We provide evidence that this mechanism may
      also explain compensation and organ size control in other physiological circuits.

PMID- 27875242
TI  - Involvement of BDNF/TrkB and ERK/CREB axes in nitroglycerin-induced rat migraine
      and effects of estrogen on these signals in the migraine.
AB  - Migraine is a highly prevalent headache disorder, especially in women. Brain
      derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinases
      (TrkB), as well as extracellular signal-regulated kinase (ERK) and its downstream
      target c-AMP-responsive element binding protein (CREB) are strongly associated
      with the transmission of nociceptive information. However, the involvement of
      these substances in migraine has rarely been examined. In the present study,
      intraperitoneal injection of nitroglycerin (NTC) successfully induced rat
      migraine attack, as evidenced by behavioral testing. The location and abundance
      of these substances in the migraine model were determined by
      immunohistochemistry, real-time polymerase chain reaction (RT-PCR), western blot
      and enzyme-linked immunosorbant assays (ELISA). Results showed that BDNF, TrkB,
      phosphor(p)-ERK and p-CREB were up-regulated in the brain neurons of both male
      and female rats with NTG-induced migraine compared to non-migraine control,
      whereas their expression levels were decreased in headache-free intervals of the
      migraine compared to migraine attacks. Estrogen is an important contributor to
      migraine. Female ovariectomized rats showed significant reduction in the
      expression of BDNF, TrkB, p-CREB and p-ERK in both attacks and intervals of NTG
      induced migraine, relative to rats that have their ovaries. But, intraperitoneal
      administration of exogenous estrogen recovered their expression in ovariectomized
      rats. Collectively, this study unveiled a positive correlation of BDNF/TrkB and
      ERK/CREB axes in NTG-induced migraine and promoting effects of estrogen on their
      signals in the migraine. These findings contribute to further understanding the
      pathogenesis of migraine in the molecular basis.

PMID- 27875243
TI  - REV-ERBalpha regulates Fgf21 expression in the liver via hepatic nuclear factor
      6.
AB  - The circadian clock contributes to the timing of many body functions including
      metabolism and reproduction. The hepatokine fibroblast growth factor 21 (FGF21)
      is a critical metabolic regulator involved in modulation of fertility. Here we
      show that lack of the clock component REV-ERBalpha elevates FGF21 levels in liver
      and plasma. At the molecular level, REV-ERBalpha modulates the expression of
      FGF21 via the liver-specific hepatic nuclear factor 6 (HNF6). We conclude that
      REV-ERBalpha regulates metabolism and reproduction, at least in part, via
      regulation of Fgf21.

PMID- 27875244
TI  - A six-genotype genetic prognostic model for papillary thyroid cancer.
AB  - A unique prognostic role of the genetic duet of BRAF V600E and TERT promoter
      mutations in papillary thyroid cancer (PTC) has been recently established, but
      the role of RAS mutation in this genetic interplay remains to be established.
      Using The Cancer Genome Atlas (TCGA) data of patients with PTC from 19 medical
      centers, we investigated the interactions among the three mutations in clinical
      outcomes of PTC. We found that BRAF and RAS mutations were mutually exclusive,
      but both were associated with TERT promoter mutations, with the genetic duet of
      BRAF/RAS and TERT mutations occurring in 34/388 (8.76%) patients. BRAF/RAS or
      TERT mutation had no or minimal effect alone, whereas coexisting BRAF/RAS and
      TERT mutations had a robust synergistic effect on poor clinicopathologic outcomes
      of PTC, including disease recurrence and patient mortality. For example, PTC
      recurrence rate was 52% with coexisting BRAF V600E/RAS and TERT promoter
      mutations vs 6.9% with no mutation, corresponding to a HR of 8.17 (95% CI 3.09
      21.58), which remained significant at 14.71 (95% CI 2.79-77.61) after adjustment
      for clinicopathologic factors and institution. BRAF/RAS mutation or TERT mutation
      alone minimally affected Kaplan-Meier patient survival curves, whereas the
      genetic duet was associated with a sharp curve decline. Thus, by confirming and
      expanding previous findings in single-institution studies, this multicenter data
      analysis establishes a six-genotype genetic prognostic model for poor outcomes of
      PTC with a risk order of genetic duet of BRAF V600E/RAS mutation and TERT
      mutation >>>>BRAF V600E = TERT mutation alone >RAS mutation alone = wild-type
      genes.

PMID- 27875245
TI  - Aryl hydrocarbon receptor is required for optimal B-cell proliferation.
AB  - The aryl hydrocarbon receptor (AhR), a transcription factor known for mediating
      xenobiotic toxicity, is expressed in B cells, which are known targets for
      environmental pollutants. However, it is unclear what the physiological functions
      of AhR in B cells are. We show here that expression of Ahr in B cells is up
      regulated upon B-cell receptor (BCR) engagement and IL-4 treatment. Addition of a
      natural ligand of AhR, FICZ, induces AhR translocation to the nucleus and
      transcription of the AhR target gene Cyp1a1, showing that the AhR pathway is
      functional in B cells. AhR-deficient (Ahr-/-) B cells proliferate less than AhR
      sufficient (Ahr+/+) cells following in vitro BCR stimulation and in vivo adoptive
      transfer models confirmed that Ahr-/- B cells are outcompeted by Ahr+/+ cells.
      Transcriptome comparison of AhR-deficient and AhR-sufficient B cells identified
      cyclin O (Ccno), a direct target of AhR, as a top candidate affected by AhR
      deficiency.

PMID- 27875246
TI  - Bimodal skin progenitors-a matter of place and time.

PMID- 27875249
TI  - An interview with Kathryn Anderson.
AB  - Kathryn Anderson is Professor and Chair of the Developmental Biology Program at
      the Sloan Kettering Institute in New York. Her lab investigates the genetic
      networks underlying the patterning and morphogenesis of the early mouse embryo.
      We caught up with Kathryn at the 2016 Society for Developmental Biology -
      International Society of Differentiation joint meeting in Boston, where she was
      awarded the Edwin G. Conklin medal.

PMID- 27875247
TI  - Comorbidity prevalence, healthcare utilization, and expenditures of Medicaid
      enrolled adults with autism spectrum disorders.
AB  - A retrospective data analysis using 2000-2008 three state Medicaid Analytic
      eXtract was conducted to examine the prevalence and association of comorbidities
      (psychiatric and non-psychiatric) with healthcare utilization and expenditures of
      fee-for-service enrolled adults (22-64 years) with and without autism spectrum
      disorders (International Classification of Diseases, Ninth Revision-clinical
      modification code: 299.xx). Autism spectrum disorder cases were 1:3 matched to no
      autism spectrum disorder controls by age, gender, and race using propensity
      scores. Study outcomes were all-cause healthcare utilization (outpatient office
      visits, inpatient hospitalizations, emergency room, and prescription drug use)
      and associated healthcare expenditures. Bivariate analyses (chi-square tests and
      t-tests), multinomial logistic regressions (healthcare utilization), and
      generalized linear models with gamma distribution (expenditures) were used.
      Adults with autism spectrum disorders (n = 1772) had significantly higher rates
      of psychiatric comorbidity (81%), epilepsy (22%), infections (22%), skin
      disorders (21%), and hearing impairments (18%). Adults with autism spectrum
      disorders had higher mean annual outpatient office visits (32ASD vs 8noASD) and
      prescription drug use claims (51ASD vs 24noASD) as well as higher mean annual
      outpatient office visits (US$4375ASD vs US$824noASD), emergency room
      (US$15,929ASD vs US$2598noASD), prescription drug use (US$6067ASD vs
      US$3144noASD), and total expenditures (US$13,700ASD vs US$8560noASD). The
      presence of a psychiatric and a non-psychiatric comorbidity among adults with
      autism spectrum disorders increased the annual total expenditures by US$4952 and
      US$5084, respectively.

PMID- 27875250
TI  - Quantitative stem cell biology: the threat and the glory.
AB  - Major technological innovations over the past decade have transformed our ability
      to extract quantitative data from biological systems at an unprecedented scale
      and resolution. These quantitative methods and associated large datasets should
      lead to an exciting new phase of discovery across many areas of biology. However,
      there is a clear threat: will we drown in these rivers of data? On 18th July
      2016, stem cell biologists gathered in Cambridge for the 5th annual Cambridge
      Stem Cell Symposium to discuss 'Quantitative stem cell biology: from molecules to
      models'. This Meeting Review provides a summary of the data presented by each
      speaker, with a focus on quantitative techniques and the new biological insights
      that are emerging.

PMID- 27875248
TI  - Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats.
AB  - Long-term high-fat diet (HFD) consumption causes cardiac dysfunction. Although
      calorie restriction (CR) has been shown to be useful in obesity, we hypothesized
      that combined CR with dipeptidyl peptidase-4 (DPP-4) inhibitor provides greater
      efficacy than monotherapy in attenuating cardiac dysfunction and metabolic
      impairment in HFD-induced obese-insulin resistant rats. Thirty male Wistar rats
      were divided into 2 groups to be fed on either a normal diet (ND, n = 6) or a HFD
      (n = 24) for 12 weeks. Then, HFD rats were divided into 4 subgroups (n =
      6/subgroup) to receive just the vehicle, CR diet (60% of mean energy intake and
      changed to ND), vildagliptin (3 mg/kg/day) or combined CR and vildagliptin for 4
      weeks. Metabolic parameters, heart rate variability (HRV), cardiac mitochondrial
      function, left ventricular (LV) and fibroblast growth factor (FGF) 21 signaling
      pathway were determined. Rats on a HFD developed insulin and FGF21 resistance,
      oxidative stress, cardiac mitochondrial dysfunction and impaired LV function.
      Rats on CR alone showed both decreased body weight and visceral fat accumulation,
      whereas vildagliptin did not alter these parameters. Rats in CR, vildagliptin and
      CR plus vildagliptin subgroups had improved insulin sensitivity and oxidative
      stress. However, vildagliptin improved heart rate variability (HRV), cardiac
      mitochondrial function and LV function better than the CR. Chronic HFD
      consumption leads to obese-insulin resistance and FGF21 resistance. Although CR
      is effective in improving metabolic regulation, vildagliptin provides greater
      efficacy in preventing cardiac dysfunction by improving anti-apoptosis and FGF21
      signaling pathways and attenuating cardiac mitochondrial dysfunction in obese
      insulin-resistant rats.

PMID- 27875255
TI  - Glycosylation pattern analysis of glycoprotein hormones and their receptors.
AB  - We have studied glycosylation patterns in glycoprotein hormones (GPHs) and
      glycoprotein hormone receptor (GPHR) extracellular domains (ECD) from different
      species to identify areas not glycosylated that could be involved in
      intermolecular or intramolecular interactions. Comparative models of the
      structure of the TSHR ECD in complex with TSH and in complex with TSHR
      autoantibodies (M22, stimulating and K1-70, blocking) were obtained based on the
      crystal structures of the FSH-FSHR ECD, M22-TSHR leucine-rich repeat domain (LRD)
      and K1-70-TSHR LRD complexes. The glycosylation sites of the GPHRs and GPHs from
      all species studied were mapped on the model of the human TSH TSHR ECD complex.
      The areas on the surfaces of GPHs that are known to interact with their receptors
      are not glycosylated and two areas free from glycosylation, not involved in
      currently known interactions, have been identified. The concave faces of GPHRs
      leucine-rich repeats 3-7 are free from glycosylation, consistent with known
      interactions with the hormones. In addition, four other non-glycosylated areas
      have been identified, two located on the receptors' convex surfaces, one in the
      long loop of the hinge regions and one at the C-terminus of the extracellular
      domains. Experimental evidence suggests that the non-glycosylated areas
      identified on the hormones and receptors are likely to be involved in forming
      intramolecular or intermolecular interactions.

PMID- 27875257
TI  - Nicotinic acid timed to feeding reverses tissue lipid accumulation and improves
      glucose control in obese Zucker rats[S].
AB  - Nicotinic acid (NiAc) is a potent inhibitor of lipolysis, acutely reducing plasma
      free fatty acid (FFA) concentrations. However, a major FFA rebound is seen during
      rapid NiAc washout, and sustained exposure is associated with tolerance
      development, with FFAs returning to pretreatment levels. Our aim was to find a
      rational NiAc dosing regimen that preserves FFA lowering, sufficient to reverse
      nonadipose tissue lipid accumulation and improve metabolic control, in obese
      Zucker rats. We compared feeding-period versus fasting-period NiAc dosing for 5
      days: 12 h subcutaneous infusion (programmable, implantable mini-pumps)
      terminated by gradual withdrawal. It was found that NiAc timed to feeding
      decreased triglycerides in liver (-47%; P < 0.01) and heart (-38%; P < 0.05) and
      reduced plasma fructosamine versus vehicle. During oral glucose tolerance test,
      plasma FFA levels were reduced with amelioration of hyperglycemia and
      hypertriglyceridemia. Furthermore, timing NiAc to feeding resulted in a general
      downregulation of de novo lipogenesis (DNL) genes in liver. By contrast, NiAc
      timed to fasting did not reduce tissue lipids, ameliorate glucose intolerance or
      dyslipidemia, or alter hepatic DNL genes. In conclusion, NiAc dosing regimen has
      a major impact on metabolic control in obese Zucker rats. Specifically, a well
      defined NiAc exposure, timed to feeding periods, profoundly improves the
      metabolic phenotype of this animal model.

PMID- 27875260
TI  - The presence and role of interstitial cells of Cajal in the proximal intestine of
      shorthorn sculpin (Myoxocephalus scorpius).
AB  - Rhythmic contractions of the mammalian gastrointestinal tract can occur in the
      absence of neuronal or hormonal stimulation owing to the generation of
      spontaneous electrical activity by interstitial cells of Cajal (ICC) that are
      electrically coupled to smooth muscle cells. The myogenically driven component of
      gastrointestinal motility patterns in fish probably also involves ICC; however,
      little is known of their presence, distribution and function in any fish species.
      In the present study, we combined immunohistochemistry and in vivo recordings of
      intestinal motility to investigate the involvement of ICC in the motility of the
      proximal intestine in adult shorthorn sculpin (Myoxocephalus scorpius).
      Antibodies against anoctamin 1 (Ano1, a Ca2+-activated Cl- channel), revealed a
      dense network of multipolar, repeatedly branching cells in the myenteric region
      of the proximal intestine, similar in many regards to the mammalian ICC-MY
      network. The addition of benzbromarone, a potent blocker of Ano1, altered the
      motility patterns seen in vivo after neural blockade with TTX. The results
      indicate that ICC are integral for the generation and propagation of the majority
      of rhythmic contractile patterns in fish, although their frequency and amplitude
      can be modulated via neural activity.

PMID- 27875251
TI  - The impact of transposable elements on mammalian development.
AB  - Despite often being classified as selfish or junk DNA, transposable elements
      (TEs) are a group of abundant genetic sequences that have a significant impact on
      mammalian development and genome regulation. In recent years, our understanding
      of how pre-existing TEs affect genome architecture, gene regulatory networks and
      protein function during mammalian embryogenesis has dramatically expanded. In
      addition, the mobilization of active TEs in selected cell types has been shown to
      generate genetic variation during development and in fully differentiated
      tissues. Importantly, the ongoing domestication and evolution of TEs appears to
      provide a rich source of regulatory elements, functional modules and genetic
      variation that fuels the evolution of mammalian developmental processes. Here, we
      review the functional impact that TEs exert on mammalian developmental processes
      and discuss how the somatic activity of TEs can influence gene regulatory
      networks.

PMID- 27875259
TI  - Monoclonal antibodies that bind to the Ly6 domain of GPIHBP1 abolish the binding
      of LPL.
AB  - GPIHBP1, an endothelial cell protein, binds LPL in the interstitial spaces and
      shuttles it to its site of action inside blood vessels. For years, studies of
      human GPIHBP1 have been hampered by an absence of useful antibodies. We reasoned
      that monoclonal antibodies (mAbs) against human GPIHBP1 would be useful for 1)
      defining the functional relevance of GPIHBP1's Ly6 and acidic domains to the
      binding of LPL; 2) ascertaining whether human GPIHBP1 is expressed exclusively in
      capillary endothelial cells; and 3) testing whether GPIHBP1 is detectable in
      human plasma. Here, we report the development of a panel of human GPIHBP1
      specific mAbs. Two mAbs against GPIHBP1's Ly6 domain, RE3 and RG3, abolished LPL
      binding, whereas an antibody against the acidic domain, RF4, did not. Also, mAbs
      RE3 and RG3 bound with reduced affinity to a mutant GPIHBP1 containing an Ly6
      domain mutation (W109S) that abolishes LPL binding. Immunohistochemistry studies
      with the GPIHBP1 mAbs revealed that human GPIHBP1 is expressed only in capillary
      endothelial cells. Finally, we created an ELISA that detects GPIHBP1 in human
      plasma. That ELISA should make it possible for clinical lipidologists to
      determine whether plasma GPIHBP1 levels are a useful biomarker of metabolic or
      vascular disease.

PMID- 27875261
TI  - The apparently contradictory energetics of hopping and running: the counter
      intuitive effect of constraints resolves the paradox.
AB  - Metabolic rate appears to increase with the rate of force application for
      running. Leg function during ground contact is similar in hopping and running, so
      one might expect that this relationship would hold for hopping as well.
      Surprisingly, metabolic rate appeared to decrease with increasing force rate for
      hopping. However, this paradox is the result of comparing different cross
      sections of the metabolic cost landscapes for hopping and running. The apparent
      relationship between metabolic rate and force rate observed in treadmill running
      is likely not a fundamental characteristic of muscle physiology, but a result of
      runners responding to speed constraints, i.e. runners selecting step frequencies
      that minimize metabolic cost per distance for a series of treadmill-specified
      speeds. Evaluating hopping metabolic rate over a narrow range of hop frequencies
      similar to that selected by treadmill runners yields energy use trends similar to
      those of running.

PMID- 27875256
TI  - Mechanistic insight into eukaryotic 60S ribosomal subunit biogenesis by cryo
      electron microscopy.
AB  - Eukaryotic ribosomes, the protein-producing factories of the cell, are composed
      of four ribosomal RNA molecules and roughly 80 proteins. Their biogenesis is a
      complex process that involves more than 200 biogenesis factors that facilitate
      the production, modification, and assembly of ribosomal components and the
      structural transitions along the maturation pathways of the pre-ribosomal
      particles. Here, I review recent structural and mechanistic insights into the
      biogenesis of the large ribosomal subunit that were furthered by cryo-electron
      microscopy of natively purified pre-60S particles and in vitro reconstituted
      ribosome assembly factor complexes. Combined with biochemical, genetic, and
      previous structural data, these structures have provided detailed insights into
      the assembly and maturation of the central protuberance of the 60S subunit, the
      network of biogenesis factors near the ribosomal tunnel exit, and the functional
      activation of the large ribosomal subunit during cytoplasmic maturation.

PMID- 27875258
TI  - Sweat lipid mediator profiling: a noninvasive approach for cutaneous research.
AB  - Recent advances in analytical and sweat collection techniques provide new
      opportunities to identify noninvasive biomarkers for the study of skin
      inflammation and repair. This study aims to characterize the lipid mediator
      profile including oxygenated lipids, endocannabinoids, and ceramides/sphingoid
      bases in sweat and identify differences in these profiles between sweat collected
      from nonlesional sites on the unflared volar forearm of subjects with and without
      atopic dermatitis (AD). Adapting routine procedures developed for plasma
      analysis, over 100 lipid mediators were profiled using LC-MS/MS and 58 lipid
      mediators were detected in sweat. Lipid mediator concentrations were not affected
      by sampling or storage conditions. Increases in concentrations of C30-C40 [NS]
      and [NdS] ceramides, and C18:1 sphingosine, were observed in the sweat of study
      participants with AD despite no differences being observed in transepidermal
      water loss between study groups, and this effect was strongest in men (P < 0.05,
      one-way ANOVA with Tukey's post hoc HSD). No differences in oxylipins and
      endocannabinoids were observed between study groups. Sweat mediator profiling may
      therefore provide a noninvasive diagnostic for AD prior to the presentation of
      clinical signs.

PMID- 27875262
TI  - Autoregulation of cardiac output is overcome by adrenergic stimulation in the
      anaconda heart.
AB  - Most vertebrates increase cardiac output during activity by elevating heart rate
      with relatively stable stroke volume. However, several studies have demonstrated
      'intrinsic autoregulation' of cardiac output where artificially increased heart
      rate is associated with decreased stroke volume, leaving cardiac output
      unchanged. We explored the capacity of noradrenaline to overcome autoregulation
      in the anaconda heart. Electrically pacing in situ perfused hearts from the
      intrinsic heart rate to the maximum attainable resulted in a proportional
      decrease in stroke volume. However, noradrenaline, which increased heart rate to
      the same frequency as pacing, maintained stroke volume and thus increased cardiac
      output. In atrial and ventricular preparations, noradrenaline significantly
      increased the force of contraction and contraction kinetics. Thus, the increased
      contractility associated with adrenergic stimulation ameliorates filling
      limitations at high heart rates. Although heart rate appears the primary
      regulated variable during activity, this may only be achieved with compensatory
      amendments in myocardial contractility provided by adrenergic stimulation.

PMID- 27875263
TI  - Reversible developmental stasis in response to nutrient availability in the
      Xenopus laevis central nervous system.
AB  - Many organisms confront intermittent nutrient restriction (NR), but the
      mechanisms to cope with nutrient fluctuations during development are not well
      understood. This is particularly true of the brain, the development and function
      of which is energy intensive. Here we examine the effects of nutrient
      availability on visual system development in Xenopus laevis tadpoles. During the
      first week of development, tadpoles draw nutrients from maternally provided yolk.
      Upon yolk depletion, animals forage for food. By altering access to external
      nutrients after yolk depletion, we identified a period of reversible stasis
      during tadpole development. We demonstrate that NR results in developmental
      stasis characterized by a decrease in overall growth of the animals, a failure to
      progress through developmental stages, and a decrease in volume of the optic
      tectum. During NR, neural progenitors virtually cease proliferation, but tadpoles
      swim and behave normally. Introducing food after temporary NR increased neural
      progenitor cell proliferation more than 10-fold relative to NR tadpoles, and cell
      proliferation was comparable to that of fed counterparts 1 week after delayed
      feeding. Delayed feeding also rescued NR-induced body length and tectal volume
      deficits and partially rescued developmental progression defects. Tadpoles
      recover from developmental stasis if food is provided within the first 9 days of
      NR, after which access to food fails to increase cell proliferation. These
      results show that early stages of tadpole brain development are acutely sensitive
      to fluctuations in nutrient availability and that NR induces developmental stasis
      from which animals can recover if food becomes available within a critical
      window.

PMID- 27875264
TI  - Expression of wnt4/5 during reproductive cycle of catfish and wnt5 promoter
      analysis.
AB  - Signaling molecules, Wnt4 and Wnt5, are essential for ovarian growth during
      developmental stages in mammals. Although these molecules were identified in
      several teleosts, their precise expression and role in reproductive processes
      have not yet been explored in any lower vertebrates. In view of this, using
      catfish, Clarias batrachus as an animal model, cloning and expression analysis of
      wnt4 and wnt5 were analyzed in different tissues, at various developmental
      stages, during ovarian reproductive cycle and after gonadotropin induction. These
      studies indicate a plausible influence of Wnts in ovarian development and
      recrudescence. Transcript and protein localization revealed their presence in
      peri-nucleolar, pre-vitellogenic, vitellogenic and follicular layer of post
      vitellogenic oocytes. Synchronous expression of pax2 and wnt5 during the ovarian
      development and recrudescence of catfish led us to analyze the importance of
      putative binding element of Pax2 in the 5'-promoter motif of wnt5 Promoter
      activity of wnt5 was analyzed by luciferase assays after transfecting progressive
      deletion constructs in pGL3 basic vector into the mammalian cell lines (HEK 293
      and CHO). The constructs having putative Pax2 motif showed high promoter activity
      compared with controls. Likewise, the constructs with site-directed mutagenesis
      showed increased activity after supplementing recombinant Pax2 indicating the
      prominence of this motif in wnt5 promoter, in vitro Electrophoretic gel mobility
      shift, supershift and chromatin immunoprecipitation assays confirmed the binding
      of Pax2 to its corresponding cis-acting element in the upstream of wnt5 This
      study is the first of its kind to report the critical transcriptional interaction
      of Pax2 on wnt5 vis-a-vis ovarian development in teleosts.

PMID- 27875265
TI  - Oviduct: roles in fertilization and early embryo development.
AB  - Animal oviducts and human Fallopian tubes are a part of the female reproductive
      tract that hosts fertilization and pre-implantation development of the embryo.
      With an increasing understanding of roles of the oviduct at the cellular and
      molecular levels, current research signifies the importance of the oviduct on
      naturally conceived fertilization and pre-implantation embryo development. This
      review highlights the physiological conditions within the oviduct during
      fertilization, environmental regulation, oviductal fluid composition and its role
      in protecting embryos and supplying nutrients. Finally, the review compares
      different aspects of naturally occurring fertilization and assisted reproductive
      technology (ART)-achieved fertilization and embryo development, giving insight
      into potential areas for improvement in this technology.

PMID- 27875266
TI  - Research in Jeopardy.

PMID- 27875267
TI  - Tributes to Daniel H. Teitelbaum, MD, PhD.

PMID- 27875268
TI  - Teduglutide and Intestinal Permeability in Short Bowel Syndrome.

PMID- 27875269
TI  - Response to "Teduglutide and Intestinal Permeability in Short Bowel Syndrome".

PMID- 27875270
TI  - JPEN Journal Club 23. GRADEing Guidelines.

PMID- 27875271
TI  - RNA-dependent disassembly of nuclear bodies.
AB  - Nuclear bodies are membraneless organelles that play important roles in genome
      functioning. A specific type of nuclear bodies known as interphase prenucleolar
      bodies (iPNBs) are formed in the nucleoplasm after hypotonic stress from
      partially disassembled nucleoli. iPNBs are then disassembled, and the nucleoli
      are reformed simultaneously. Here, we show that diffusion of B23 molecules (also
      known as nucleophosmin, NPM1) from iPNBs, but not fusion of iPNBs with the
      nucleoli, contributes to the transfer of B23 from iPNBs to the nucleoli.
      Maturation of pre-ribosomal RNAs (rRNAs) and the subsequent outflow of mature
      rRNAs from iPNBs led to the disassembly of iPNBs. We found that B23 transfer was
      dependent on the synthesis of pre-rRNA molecules in nucleoli; these pre-rRNA
      molecules interacted with B23 and led to its accumulation within nucleoli. The
      transfer of B23 between iPNBs and nucleoli was accomplished through a
      nucleoplasmic pool of B23, and increased nucleoplasmic B23 content retarded
      disassembly, whereas B23 depletion accelerated disassembly. Our results suggest
      that iPNB disassembly and nucleolus assembly might be coupled through RNA
      dependent exchange of nucleolar proteins, creating a highly dynamic system with
      long-distance correlations between spatially distinct processes.

PMID- 27875272
TI  - Tenascin-C at a glance.
AB  - Tenascin-C (TNC) is a hexameric, multimodular extracellular matrix protein with
      several molecular forms that are created through alternative splicing and protein
      modifications. It is highly conserved amongst vertebrates, and molecular
      phylogeny indicates that it evolved before fibronectin. Tenascin-C has many
      extracellular binding partners, including matrix components, soluble factors and
      pathogens; it also influences cell phenotype directly through interactions with
      cell surface receptors. Tenascin-C protein synthesis is tightly regulated, with
      widespread protein distribution in embryonic tissues, but restricted distribution
      of tenascin-C in adult tissues. Tenascin-C is also expressed de novo during wound
      healing or in pathological conditions, including chronic inflammation and cancer.
      First described as a modulator of cell adhesion, tenascin-C also directs a
      plethora of cell signaling and gene expression programs by shaping mechanical and
      biochemical cues within the cellular microenvironment. Exploitment of the
      pathological expression and function of tenascin-C is emerging as a promising
      strategy to develop new diagnostic, therapeutic and bioengineering tools. In this
      Cell Science at a Glance article and the accompanying poster we provide a
      succinct and comprehensive overview of the structural and functional features of
      tenascin-C and its potential roles in developing embryos and under pathological
      conditions.

PMID- 27875273
TI  - SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation.
AB  - Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase known to regulate microtubule
      dynamics and cell cycle progression. SIRT2 has also been implicated in the
      pathology of cancer, neurodegenerative diseases and progeria. Here, we show that
      SIRT2 depletion or overexpression causes nuclear envelope reassembly defects. We
      link this phenotype to the recently identified regulator of nuclear envelope
      reassembly ANKLE2. ANKLE2 acetylation at K302 and phosphorylation at S662 are
      dynamically regulated throughout the cell cycle by SIRT2 and are essential for
      normal nuclear envelope reassembly. The function of SIRT2 therefore extends
      beyond the regulation of microtubules to include the regulation of nuclear
      envelope dynamics.

PMID- 27875274
TI  - SIRT1 inhibits EV71 genome replication and RNA translation by interfering with
      the viral polymerase and 5'UTR RNA.
AB  - Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that
      contains a single open reading frame (ORF) flanked by a 5' untranslated region
      (5'UTR) and a polyadenylated 3'UTR. Here, we demonstrated that EV71 activates the
      production of silent mating type information regulation 2 homolog 1 (SIRT1), a
      histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and
      deacetylase activity, and enhances SIRT1 translocation from the nucleus to the
      cytoplasm. More interestingly, activated SIRT1 subsequently binds with the EV71
      3Dpol protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the
      acetylation and RdRp activity of 3Dpol, resulting in the attenuation of viral
      genome replication. Moreover, SIRT1 interacts with the cloverleaf structure of
      the EV71 RNA 5'UTR to inhibit viral RNA transcription, and binds to the internal
      ribosome entry site (IRES) of the EV71 5'UTR to attenuate viral RNA translation.
      Thus, EV71 stimulates SIRT1 production and activity, which in turn represses EV71
      genome replication by inhibiting viral polymerase, and attenuates EV71 RNA
      transcription and translation by interfering with viral RNA. These results
      uncover a new function of SIRT1 and reveal a new mechanism underlying the
      regulation of EV71 replication.

PMID- 27875275
TI  - Histone chaperone APLF regulates induction of pluripotency in murine fibroblasts.
AB  - Induction of pluripotency in differentiated cells through the exogenous
      expression of the transcription factors Oct4, Sox2, Klf4 and cellular Myc
      involves reprogramming at the epigenetic level. Histones and their metabolism
      governed by histone chaperones constitute an important regulator of epigenetic
      control. We hypothesized that histone chaperones facilitate or inhibit the course
      of reprogramming. For the first time, we report here that the downregulation of
      histone chaperone Aprataxin PNK-like factor (APLF) promotes reprogramming by
      augmenting the expression of E-cadherin (Cdh1), which is implicated in the
      mesenchymal-to-epithelial transition (MET) involved in the generation of induced
      pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs).
      Downregulation of APLF in MEFs expedites the loss of the repressive MacroH2A.1
      (encoded by H2afy) histone variant from the Cdh1 promoter and enhances the
      incorporation of active histone H3me2K4 marks at the promoters of the
      pluripotency genes Nanog and Klf4, thereby accelerating the process of cellular
      reprogramming and increasing the efficiency of iPSC generation. We demonstrate a
      new histone chaperone (APLF)-MET-histone modification cohort that functions in
      the induction of pluripotency in fibroblasts. This regulatory axis might provide
      new mechanistic insights into perspectives of epigenetic regulation involved in
      cancer metastasis.

PMID- 27875278
TI  - Ratiometric analysis of Acridine Orange staining in the study of acidic
      organelles and autophagy.
AB  - Acridine Orange is a cell-permeable green fluorophore that can be protonated and
      trapped in acidic vesicular organelles (AVOs). Its metachromatic shift to red
      fluorescence is concentration-dependent and, therefore, Acridine Orange
      fluoresces red in AVOs, such as autolysosomes. This makes Acridine Orange
      staining a quick, accessible and reliable method to assess the volume of AVOs,
      which increases upon autophagy induction. Here, we describe a ratiometric
      analysis of autophagy using Acridine Orange, considering the red-to-green
      fluorescence intensity ratio (R/GFIR) to quantify flow cytometry and fluorescence
      microscopy data of Acridine-Orange-stained cells. This method measured with
      accuracy the increase in autophagy induced by starvation or rapamycin, and the
      reduction in autophagy produced by bafilomycin A1 or the knockdown of Beclin1 or
      ATG7. Results obtained with Acridine Orange, considering R/GFIR, correlated with
      the conversion of the unlipidated form of LC3 (LC3-I) into the lipidated form
      (LC3-II), SQSTM1 degradation and GFP-LC3 puncta formation, thus validating this
      assay to be used as an initial and quantitative method for evaluating the late
      step of autophagy in individual cells, complementing other methods.

PMID- 27875279
TI  - Biochemical Markers of Nutrition Support in Critically Ill Trauma Victims.
AB  - BACKGROUND: In critically ill patients, plasma serum albumin and transthyretin
      concentrations are thought to reflect the effects of acute illness, including
      resuscitation and inflammation. Their use as markers for preexisting nutrition
      status is, therefore, not recommended. Whether they can be used to assess
      subsequent effectiveness of artificial nutrition support is unclear. We sought to
      determine if these biomarkers are associated with enteral caloric intake in
      critically ill trauma patients. MATERIALS AND METHODS: We analyzed data from
      adult trauma victims who required >=2 days of mechanical ventilation and >=7 days
      of intensive care. We categorized patients into low, middle, or high enteral
      calorie delivery groups (2, 9, or 17 kcal/kg/d during the first week). We
      compared serial concentrations of serum albumin, transthyretin, and C-reactive
      protein. Multiple linear and Poisson regression were used to determine
      relationships between calorie intake and nutrition biomarkers. RESULTS: In total,
      1056 patients were analyzed. Their median age was 44 (interquartile range [IQR],
      28-57) years, and median injury severity score was 34 (IQR, 26-41). Calorie
      intake during the first week was not related to biomarkers during the first or
      second week. However, by the beginning of the third week, the highest calorie
      group showed greater changes in concentrations of transthyretin (+3.0 mg/dL
      relative to initial concentration, P = .01) and serum albumin (+0.17 g/dL, P =
      .05) compared with the lowest calorie group. CONCLUSIONS: In trauma patients
      requiring 1 or more weeks of intensive care, changes in transthyretin were
      associated with enteral caloric intake. Our data suggest that transthyretin could
      be used to monitor nutrition support after 2 weeks in intensive care.

PMID- 27875280
TI  - Malnutrition Identified by the Academy of Nutrition and Dietetics and American
      Society for Parenteral and Enteral Nutrition Consensus Criteria and Other Bedside
      Tools Is Highly Prevalent in a Sample of Individuals Undergoing Treatment for
      Head and Neck Cancer.
AB  - BACKGROUND: Using the Academy of Nutrition and Dietetics and American Society for
      Parenteral and Enteral Nutrition (Academy/ASPEN) Consensus malnutrition
      definition, we estimated malnutrition prevalence in a sample of individuals with
      head and neck cancer (HNC) and compared it with the Patient-Generated Subjective
      Global Assessment (PG-SGA). We also investigated the utility of the 50-kHz phase
      angle (PA) and 200-kHz/5-kHz impedance ratio (IR) to identify malnutrition.
      MATERIALS AND METHODS: Nineteen individuals (18 males, 1 female) scheduled to
      undergo chemoradiotherapy were seen at 5 time points during and up to 3 months
      after treatment completion. Multiple-frequency bioelectrical impedance analysis,
      PG-SGA, nutrition-focused physical examination, anthropometry, dietary intake,
      and handgrip strength data were collected. RESULTS: Using the Consensus, 67% were
      found to be malnourished before treatment initiation; these criteria diagnosed
      malnutrition with overall good sensitivity (94%) and moderate specificity (43%)
      compared with PG-SGA. Over all pooled observations, "malnourished" (by Consensus
      but not PG-SGA category) had a lower mean PA (5.2 vs 5.9; P = .03) and higher IR
      (0.82 vs 0.79; P = .03) than "well-nourished" categorizations, although the
      clinical relevance of these findings is unclear. PA and IR were correlated with
      higher PG-SGA score (r = -0.35, r = 0.36; P < .01) and handgrip strength (r =
      0.48, r = -0.47; P < .01). CONCLUSION: The Academy/ASPEN Consensus and the PG-SGA
      were in good agreement. It is unclear whether PA and IR can be used as surrogate
      markers of nutrition status or muscle loss.

PMID- 27875281
TI  - Effect of Liraglutide Treatment on Jejunostomy Output in Patients With Short
      Bowel Syndrome: An Open-Label Pilot Study.
AB  - BACKGROUND: An impaired hormonal "ileo-colonic brake" may contribute to rapid
      gastric emptying, gastric hypersecretion, high ostomy losses, and the need for
      parenteral support in end-jejunostomy short bowel syndrome (SBS) patients with
      intestinal failure (IF). Liraglutide, a glucagon-like peptide 1 receptor agonist,
      may reduce gastric hypersecretion and dampen gastric emptying, thereby improving
      conditions for intestinal absorption. MATERIALS AND METHODS: In an 8-week, open
      label pilot study, liraglutide was given subcutaneously once daily to 8 end
      jejunostomy patients, aged 63.4 +/- 10.9 years (mean +/- SD) and with small bowel
      lengths of 110 +/- 66 cm. The 72-hour metabolic balance studies were performed
      before and at the end of treatment. Food intake was unrestricted. Oral fluid
      intake and parenteral support volume were kept constant. The primary end point
      was change in the ostomy wet weight output. RESULTS: Liraglutide reduced ostomy
      wet weight output by 474 +/- 563 g/d from 3249 +/- 1352 to 2775 +/- 1187 g/d (P =
      .049, Student t test). Intestinal wet weight absorption tended to increase by 464
      +/- 557 g/d (P = .05), as did urine production by 765 +/- 759 g/d (P = .02).
      Intestinal energy absorption improved by 902 +/- 882 kJ/d (P = .02). CONCLUSION:
      Liraglutide reduced ostomy wet weight output in end-jejunostomy patients with SBS
      IF and increased their intestinal wet weight and energy absorption. If larger,
      randomized, placebo-controlled studies confirm these effects, it adds to the
      hypothesis that many ileo-colonic brake hormones in conjunction may be involved
      in the process of intestinal adaptation. By identification of key hormones and
      addressing their potential synergistic effects, better treatments may be provided
      to patients with SBS-IF. This trial was registered at clinicaltrialsregister.eu
      as 2013-005499-16.

PMID- 27875282
TI  - Metabolic Requirement of Septic Shock Patients Before and After Liberation From
      Mechanical Ventilation.
AB  - OBJECTIVES: This study identified the difference in energy expenditure and
      substrate utilization of patients during and upon liberation from mechanical
      ventilation. METHODS: Patients under intensive care who were diagnosed with
      septic shock and dependent on mechanical ventilation were recruited. Indirect
      calorimetry measurements were performed during and upon liberation from
      mechanical ventilation. RESULTS: Thirty-five patients were recruited (20 men and
      15 women; mean age, 69 +/- 10 years). Measured energy expenditures during
      ventilation and upon liberation were 2090 +/- 489 kcal.d-1 and 1910 +/- 579
      kcal.d-1, respectively ( P < .05). Energy intake was provided at 1148 +/- 495
      kcal.d-1 and differed significantly from all measured energy expenditures ( P <
      .05). Mean carbohydrate utilization was 0.19 +/- 0.1 g.min-1 when patients were
      on mechanical ventilation compared with 0.15 +/- 0.09 g.min-1 upon liberation ( P
      < .05). Mean lipid oxidation was 0.08 +/- 0.05 g.min-1 during and 0.09 +/- 0.07
      g.min-1 upon liberation from mechanical ventilation ( P > .05). CONCLUSIONS:
      Measured energy expenditure was higher during than upon liberation from
      mechanical ventilation. This could be the increase in work of breathing from the
      continuous positive pressure support, repeated weaning cycles from mechanical
      ventilation, and/or the asynchronization between patients' respiration and
      ventilator support. Future studies should examine whether more appropriately
      matching energy expenditure with energy intake would promote positive health
      outcomes.

PMID- 27875277
TI  - Development of nanoscale structure in LAT-based signaling complexes.
AB  - The adapter molecule linker for activation of T cells (LAT) plays a crucial role
      in forming signaling complexes induced by stimulation of the T cell receptor
      (TCR). These multi-molecular complexes are dynamic structures that activate
      highly regulated signaling pathways. Previously, we have demonstrated nanoscale
      structure in LAT-based complexes where the adapter SLP-76 (also known as LCP2)
      localizes to the periphery of LAT clusters. In this study, we show that initially
      LAT and SLP-76 are randomly dispersed throughout the clusters that form upon TCR
      engagement. The segregation of LAT and SLP-76 develops near the end of the
      spreading process. The local concentration of LAT also increases at the same
      time. Both changes require TCR activation and an intact actin cytoskeleton. These
      results demonstrate that the nanoscale organization of LAT-based signaling
      complexes is dynamic and indicates that different kinds of LAT-based complexes
      appear at different times during T cell activation.

PMID- 27875276
TI  - Cancer cells become less deformable and more invasive with activation of beta
      adrenergic signaling.
AB  - Invasion by cancer cells is a crucial step in metastasis. An oversimplified view
      in the literature is that cancer cells become more deformable as they become more
      invasive. beta-adrenergic receptor (betaAR) signaling drives invasion and
      metastasis, but the effects on cell deformability are not known. Here, we show
      that activation of beta-adrenergic signaling by betaAR agonists reduces the
      deformability of highly metastatic human breast cancer cells, and that these
      stiffer cells are more invasive in vitro We find that betaAR activation also
      reduces the deformability of ovarian, prostate, melanoma and leukemia cells.
      Mechanistically, we show that betaAR-mediated cell stiffening depends on the
      actin cytoskeleton and myosin II activity. These changes in cell deformability
      can be prevented by pharmacological beta-blockade or genetic knockout of the
      beta2-adrenergic receptor. Our results identify a beta2-adrenergic-Ca2+-actin
      axis as a new regulator of cell deformability, and suggest that the relationship
      between cell mechanical properties and invasion might be dependent on context.

PMID- 27875283
TI  - Does Persistent Inflammatory Catabolic Syndrome Exist in Critically Ill Neonates?
AB  - BACKGROUND: Persistent inflammatory catabolic syndrome (PICS) has not been
      described in the infant population. This study proposes a definition of PICS in
      critically ill infants. METHODS: A published adult criterion of PICS was modified
      using anthropometric and biochemical reference ranges for infants. A prospective
      chart review of admissions to a tertiary surgical neonatal intensive care unit
      (NICU) was performed over 65 days. Demographic, anthropometric, biochemical, and
      other clinical variables such as length of stay and medication use were collected
      daily throughout admission. Infants were categorized as having or not having
      PICS. RESULTS: Twenty percent of admitted infants (n = 15) developed PICS using
      the proposed criteria. Infants with PICS were more likely to be classified as
      failure to thrive (53%), meeting only 75% of their anticipated weight gain.
      Significantly more infants with PICS had undergone surgery (100%; P = .01),
      received inotropic medication (40%; P = .05), and had longer NICU and total
      hospital length of stay ( P < .001 and P < .001). Infants with PICS had higher
      peak glucose levels (11.8 +/- 7.3 mmol/L) and elevated urea concentrations (7.9
      +/- 4.6 mmol/L). CONCLUSIONS: PICS does exist in a critically ill neonatal
      population and may be identified using the definition proposed in this study.
      Infants with PICS displayed metabolic dysregulation, impaired expected growth
      velocity, and longer length of stay despite no differences in severity scores or
      diagnosis between the groups. Validation of this work is required, and research
      into timely identification of infants with PICS is needed to inform whether these
      infants would benefit from earlier and novel nutrition intervention.

PMID- 27875284
TI  - Parenteral Nutrition Electrolyte Abnormalities and Associated Factors Before and
      After Nutrition Support Team Initiation.
AB  - BACKGROUND: Studied since the 1940s, refeeding syndrome still has no universal
      definition, thus making comparison of studies difficult. Negative outcomes (eg,
      metabolic abnormalities) may occur with the use of specialized nutrition, such as
      parenteral nutrition (PN). Less than half of medical institutions have a
      nutrition support team (NST) managing PN. Interdisciplinary team management of PN
      may reduce negative outcomes of PN. The objective of this study was to show the
      value of the NST by measuring differences in PN variables, especially electrolyte
      abnormalities (EAs), before and after NST initiation at a large medical center
      and to identify factors associated with EAs among adult subjects receiving PN.
      MATERIALS AND METHODS: During this retrospective study, computerized medical
      charts (N = 735) from 2007-2010 were reviewed for electrolyte changes
      (particularly potassium, magnesium, and phosphorus) the first 3 days following PN
      initiation in hospitalized adults. Changes in EAs with other variables were
      compared before and after NST implementation. Equivalent samples sizes were
      collected to better evaluate the impact of the team. RESULTS: Following the
      implementation of the NST, fewer EAs were seen in PN patients (53%; chi2 =
      10.906, P = .004); significantly less potassium, phosphorus, and magnesium
      intravenous piggyback supplementation (88.8% vs 94%; chi2 = 5.05, P = .026) was
      used; and mortality within 30 days of PN cessation was significantly less (12.7%
      vs 10.6%, P = .012). CONCLUSION: Our study complements existing research, finding
      that an NST was associated with a decreased occurrence of EAs and mortality in
      the hospitalized adult receiving PN.

PMID- 27875285
TI  - What Is "Best Achievable" Practice in Implementing the Enhanced Protein-Energy
      Provision via the Enteral Route Feeding Protocol in Intensive Care Units in the
      United States? Results of a Multicenter, Quality Improvement Collaborative.
AB  - BACKGROUND: The purpose of this study was to determine what was "best achievable
      practice" with the implementation of a novel enteral feeding protocol (Enhanced
      Protein-Energy Provision via the Enteral Route Feeding Protocol [PEP uP
      protocol]). METHODS: This study was a multicenter quality improvement
      collaborative wherein we describe nutrition practices and outcomes within PEP uP
      sites. We report the minimum, average, and maximal site-level performance on
      aspects related to nutrition practices and outcomes. RESULTS: In 2014, 7
      intensive care units (ICUs) in the United States implemented the PEP uP protocol.
      On average, over the first 5 ICU days, patients received 35% (site range, 26%
      53%) of their prescribed energy requirements and 42% (site range, 29%-66%) of
      their prescribed protein requirements from enteral nutrition. In PEP uP sites,
      71% (site range, 58%-95%) of patients received a semidigested formula within 72
      hours of admission to the ICU, 72% had a volume-based goal as the initial feeding
      strategy (site range, 47%-100%), 56% had prophylactic protein supplements (site
      range, 0%-100%), and 19% received prophylactic motility agents (site range, 0%
      85%). CONCLUSIONS: There was variable success with the implementation of the
      different components of the PEP uP protocol. Improving the implementation of the
      various components may further increase nutrition delivery.

PMID- 27875286
TI  - New, Immunomodulatory, Oral Nutrition Formula for Use Prior to Surgery in
      Patients With Head and Neck Cancer: An Exploratory Study.
AB  - BACKGROUND: The perioperative use of immunomodulatory nutrition formulas in
      patients with head and neck cancer reduces the number of postoperative infections
      and the length of hospital stay. OBJECTIVE: An exploratory, randomized,
      controlled, blind, clinical trial was designed to examine the effect of the
      preoperative consumption of a new, immunomodulatory, oral nutrition formula in
      patients with head and neck cancer. METHODS: Thirty-eight patients were
      randomized to receive either 400 mL/d of either the new immunomodulatory formula
      (IF) or that commonly used in clinical practice (CF) over 10 days prior to
      surgery. Thirty-three patients completed the study. Compliance, tolerance, the
      length of hospital stay, the incidence of infections and noninfectious
      complications before discharge, and the same up to 15 and 30 days after discharge
      were recorded. RESULTS: The percentage of patients who developed infections
      before discharge was significantly lower in the IF than in the CF group (P =
      .013), as was the number of infections/100 patients/d (P = .035). The length of
      hospital stay was significantly shorter in the IF group (P = .001). Both formulas
      were safe and well tolerated. No other differences were detected. These results
      suggest preoperative consumption of the new formula to be beneficial for patients
      with neck and head cancer. Further trials are needed to confirm these results and
      to test the efficacy of the formula in patients with other conditions.
      CONCLUSION: The new formula can be safely prescribed as part of the preoperative
      treatment of patients with head and neck cancer and might reduce the problem of
      postoperative infection.

PMID- 27875287
TI  - Two-Year Follow-up of a Randomized Controlled Nutrition Intervention Trial in
      Very Low-Birth-Weight Infants.
AB  - BACKGROUND: Very low-birth-weight (VLBW) infants are at risk for neurodevelopment
      impairment. This study assessed the effect of early aggressive parenteral
      nutrition (PN) on long-term outcome in VLBW infants. MATERIALS AND METHODS:
      Directly after birth, VLBW infants (birth weight <1500 g, n = 142) were
      randomized to 5 different PN regimes. Controls (n = 46) received glucose and
      standard-dose amino acids (AAs; 2.4 g/[kg.d]) from birth onward and pure soybean
      oil fat emulsion (SOY) on the second day of life. Two intervention groups
      received glucose, standard-dose AAs, and lipids from birth onward: SOY (n = 24)
      or mixed fat emulsion (MIX, n = 25). The 2 other intervention groups received
      glucose, high-dose AAs (3.6 g/[kg.d]), and lipids from birth onward: SOY (n = 24)
      or MIX (n = 23). The primary outcome of this follow-up study was the composite
      outcome of "death or major disability" at 2 years corrected age. Secondary
      outcomes were death, major disabilities, neurodevelopmental scores, and
      anthropometry. RESULTS: Follow-up rate was 92% (n = 134). Thirty-five (26%)
      infants had died or had a major disability, with no differences between
      intervention groups and controls. Increased odds for death were observed in the
      standard-dose AA-MIX group (odds ratio, 5.4; 95% confidence interval [CI], 1.1
      27.0). Neurodevelopmental scores and incidence of major disabilities did not
      differ between groups. Growth in the high-dose AA-MIX group was enhanced compared
      with growth in controls at 2 years corrected age (+0.51 [0.01-1.02] weight SDS).
      CONCLUSION: This randomized controlled hypothesis-generating study demonstrated
      no beneficial effect of early high-dose AA administration and mixed fat emulsions
      on survival and neurodevelopmental outcome in VLBW infants, although growth was
      enhanced.

PMID- 27875289
TI  - Home Parenteral Nutrition in Adult Patients With Chronic Intestinal Failure:
      Catheter-Related Complications Over 4 Decades at the Main Danish Tertiary
      Referral Center.
AB  - BACKGROUND/AIMS: Catheter-related complications (CRCs) cause mortality and
      morbidity in patients dependent on parenteral support at home (HPN) due to
      intestinal failure (IF). This study describes the incidences of CRCs in an adult
      IF cohort over 40 years. It illustrates the evolution and consequences of CRCs,
      their association to demographic characteristics, and potential risk factors in
      an effort to provide the rationale for preventive precautions to the relevant
      patients with IF at risk. METHODS: All patients with IF discharged with HPN from
      1970-2010 were included. Patient and treatment characteristics were extracted
      from the Copenhagen IF database. The incidences were given per 1000 central
      venous catheter (CVC) days. RESULTS: The 1715 CRCs occurred in 70% of the 508
      patients with IF (56% of the 2191 CVCs). The incidence of catheter-related
      bloodstream infections (CRBSIs) was 1.43. Higher age, HPN administration by
      community home nurses, and prior CRBSIs significantly raised the hazard for
      CRBSIs. In the 1970s, catheters were generally replaced following CRBSIs, whereas
      catheter salvage was the norm in the 2000s. The incidences of mechanical
      complications, tunnel infections, and catheter-related venous thromboses were
      0.80, 0.25, and 0.11, respectively. The overall CRC incidence was 2.58,
      decreasing the first 3 decades but peaking in the last (2.84). The deaths related
      to CRCs were low (0.018). CONCLUSION: Even in an experienced IF center of
      excellence, the incidence of CRCs increased over the 4 decades. This increase
      could be explained by the expansion of the indication of HPN to a more elderly
      and frail patient population.

PMID- 27875290
TI  - Whole Body Protein Turnover and Net Protein Balance After Pediatric Thoracic
      Surgery: A Noninvasive Single-Dose 15N Glycine Stable Isotope Protocol With End
      Product Enrichment.
AB  - BACKGROUND: We used the 15N glycine urinary end-product enrichment technique to
      quantify whole body protein turnover following thoracic surgery. MATERIALS AND
      METHODS: A single dose of 15N glycine (2 mg/kg) was administered orally on
      postoperative day 1 to children (1-18 years) following thoracic surgery. 15N
      enrichment of ammonia and urea was measured in mixed urine after 12 and 24 hours,
      respectively, and protein synthesis, breakdown, and net balance determined.
      Nitrogen balance (dietary intake minus urinary excretion) was calculated. Urinary
      3-methylhistidine:creatinine ratio was measured as a marker of skeletal muscle
      protein breakdown. RESULTS: We enrolled 19 subjects-median (interquartile range):
      age, 13.8 years (12.2-15.1); weight, 49.2 kg (38.4-60.8)-who underwent
      thoracotomy (n = 12) or thoracoscopic (n = 7) surgery. Protein synthesis and
      breakdown by 15N enrichment were 7.1 (5.5-9) and 7.1 (5.6-9) g.kg-1.d-1 with
      ammonia (12 hours) as the end product, and 5.8 (3.8-6.7) and 6.7 (4.5-7.6) with
      urea (24 hours), respectively. Net protein balance by the 15N glycine and urinary
      urea nitrogen methods were -0.34 (-0.47, -0.3) and -0.48 (-0.65, -0.28) g.kg-1.d
      1, respectively (rs = 0.828, P < .001). Postoperative change in 3
      methylhistidine:creatinine ratio did not correlate significantly with protein
      breakdown or balance. CONCLUSION: The single-dose oral administration of 15N
      glycine stable isotope with measurement of urinary end-product enrichment is a
      feasible and noninvasive method to investigate whole body protein turnover in
      children. After major surgery, children manifest increased protein turnover and
      net negative balance due to increased protein breakdown.

PMID- 27875291
TI  - Independence From Parenteral Nutrition and Intravenous Fluid Support During
      Treatment With Teduglutide Among Patients With Intestinal Failure Associated With
      Short Bowel Syndrome.
AB  - BACKGROUND: In phase III clinical studies, treatment with teduglutide was
      associated with clinically meaningful reductions (>=20% from baseline) in
      parenteral support (PS; parenteral nutrition and/or intravenous fluids)
      requirements in adult patients with intestinal failure associated with short
      bowel syndrome (SBS-IF). This analysis reports clinical characteristics of
      patients who achieved complete independence from PS during teduglutide treatment.
      MATERIALS AND METHODS: Post hoc analysis of adult patients who achieved complete
      PS independence during treatment with teduglutide 0.05 mg/kg/d. Data were pooled
      from 5 teduglutide clinical trials (2 phase III placebo-controlled trials
      [NCT00081458 and NCT00798967] and their respective extension studies
      [NCT00172185, NCT00930644, NCT01560403]). Descriptive statistics were used; no
      between-group comparisons were performed because of the small sample size and
      lack of comparator. RESULTS: Of 134 patients, 16 gained oral or enteral autonomy
      after a median of 5 years of PS dependence and 89 weeks of teduglutide treatment.
      Demographic and baseline disease characteristics varied among patients (median
      age, 55 years; 50% men; median baseline PS volume, 5.1 L/wk; median residual
      small intestine length, 52.5 cm). Most patients who achieved PS independence had
      colon-in-continuity; however, there was no significant difference in the
      frequency of PS independence among patients who maintained colon-in-continuity vs
      those who did not. CONCLUSION: Findings from this post hoc analysis suggest that
      oral or enteral autonomy is possible for some patients with SBS-IF who are
      treated with teduglutide, regardless of baseline characteristics and despite long
      term PS dependence.

PMID- 27875292
TI  - Dissociation of Golgi-associated DHHC-type Zinc Finger Protein (GODZ)- and
      Sertoli Cell Gene with a Zinc Finger Domain-beta (SERZ-beta)-mediated
      Palmitoylation by Loss of Function Analyses in Knock-out Mice.
AB  - The gamma2 subunit of GABA type A receptors (GABAARs) is thought to be subject to
      palmitoylation by both Golgi-associated DHHC-type zinc finger protein (GODZ; also
      known as DHHC3) and its paralog Sertoli cell gene with a zinc finger domain-beta
      (SERZ-beta; DHHC7) based on overexpression of enzymes and substrates in
      heterologous cells. Here we have further investigated the substrate specificity
      of these enzymes by characterization of GODZ and SERZ-beta knock-out (KO) mice as
      well as double KO (DKO) neurons. Palmitoylation of gamma2 and a second substrate,
      growth-associated protein of 43 kDa, that is independently implicated in
      trafficking of GABAARs was significantly reduced in brain of GODZ KO versus wild
      type (WT) mice but unaltered in SERZ-beta KO mice. Accumulation of GABAARs at
      synapses, GABAergic innervation, and synaptic function were reduced in GODZ KO
      and DKO neurons to a similar extent, indicating that SERZ-beta does not
      contribute to palmitoylation or trafficking of GABAARs even in the absence of
      GODZ. Notably, these effects were seen only when mutant neurons were grown in
      competition with WT neurons, thereby mimicking conditions of shRNA-transfected
      neurons previously used to characterize GODZ. However, GABA-evoked whole-cell
      currents of DKO neurons and the GABAAR cell surface expression in DKO neurons and
      GODZ or SERZ-beta KO brain slices were unaltered, indicating that GODZ-mediated
      palmitoylation selectively controls the pool of receptors at synapses. The
      different substrate specificities of GODZ and SERZ-beta in vivo were correlated
      with their differential localization to cis- versus trans-Golgi compartment, a
      mechanism that was compromised by overexpression of GODZ.

PMID- 27875293
TI  - Attenuation of Blood-Brain Barrier Breakdown and Hyperpermeability by Calpain
      Inhibition.
AB  - Blood-brain barrier (BBB) breakdown and the associated microvascular
      hyperpermeability followed by brain edema are hallmark features of several brain
      pathologies, including traumatic brain injuries (TBI). Recent studies indicate
      that pro-inflammatory cytokine interleukin-1beta (IL-1beta) that is up-regulated
      following traumatic injuries also promotes BBB dysfunction and hyperpermeability,
      but the underlying mechanisms are not clearly known. The objective of this study
      was to determine the role of calpains in mediating BBB dysfunction and
      hyperpermeability and to test the effect of calpain inhibition on the BBB
      following traumatic insults to the brain. In these studies, rat brain
      microvascular endothelial cell monolayers exposed to calpain inhibitors (calpain
      inhibitor III and calpastatin) or transfected with calpain-1 siRNA demonstrated
      attenuation of IL-1beta-induced monolayer hyperpermeability. Calpain inhibition
      led to protection against IL-1beta-induced loss of zonula occludens-1 (ZO-1) at
      the tight junctions and alterations in F-actin cytoskeletal assembly. IL-1beta
      treatment had no effect on ZO-1 gene (tjp1) or protein expression. Calpain
      inhibition via calpain inhibitor III and calpastatin decreased IL-1beta-induced
      calpain activity significantly (p < 0.05). IL-1beta had no detectable effect on
      intracellular calcium mobilization or endothelial cell viability. Furthermore,
      calpain inhibition preserved BBB integrity/permeability in a mouse controlled
      cortical impact model of TBI when studied using Evans blue assay and intravital
      microscopy. These studies demonstrate that calpain-1 acts as a mediator of IL
      1beta-induced loss of BBB integrity and permeability by altering tight junction
      integrity, promoting the displacement of ZO-1, and disorganization of
      cytoskeletal assembly. IL-1beta-mediated alterations in permeability are neither
      due to the changes in ZO-1 expression nor cell viability. Calpain inhibition has
      beneficial effects against TBI-induced BBB hyperpermeability.

PMID- 27875294
TI  - Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2
      Expression in Neurons: OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP
      RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1).
AB  - Burgeoning evidence supports a role for cyclooxygenase metabolites in regulating
      membrane excitability in various forms of synaptic plasticity. Two
      cyclooxygenases, COX-1 and COX-2, catalyze the initial step in the metabolism of
      arachidonic acid to prostaglandins. COX-2 is generally considered inducible, but
      in glutamatergic neurons in some brain regions, including the cerebral cortex, it
      is constitutively expressed. However, the transcriptional mechanisms by which
      this occurs have not been elucidated. Here, we used quantitative PCR and also
      analyzed reporter gene expression in a mouse line carrying a construct consisting
      of a portion of the proximal promoter region of the mouse COX-2 gene upstream of
      luciferase cDNA to characterize COX-2 basal transcriptional regulation in
      cortical neurons. Extracts from the whole brain and from the cerebral cortex,
      hippocampus, and olfactory bulbs exhibited high luciferase activity. Moreover,
      constitutive COX-2 expression and luciferase activity were detected in cortical
      neurons, but not in cortical astrocytes, cultured from wild-type and transgenic
      mice, respectively. Constitutive COX-2 expression depended on spontaneous but not
      evoked excitatory synaptic activity and was shown to be N-methyl-d-aspartate
      receptor-dependent. Constitutive promoter activity was reduced in neurons
      transfected with a dominant-negative cAMP response element binding protein (CREB)
      and was eliminated by mutating the CRE-binding site on the COX-2 promoter.
      However, mutation of the stimulatory protein-1 (Sp1)-binding site resulted in an
      N-methyl-d-aspartate receptor-dependent enhancement of COX-2 promoter activity.
      Basal binding of the transcription factors CREB and Sp1 to the native neuronal
      COX-2 promoter was confirmed. In toto, our data suggest that spontaneous
      glutamatergic synaptic activity regulates constitutive neuronal COX-2 expression
      via Sp1 and CREB protein-dependent transcriptional mechanisms.

PMID- 27875295
TI  - Key Residues and Phosphate Release Routes in the Saccharomyces cerevisiae Pho84
      Transceptor: THE ROLE OF TYR179 IN FUNCTIONAL REGULATION.
AB  - Pho84, a major facilitator superfamily (MFS) protein, is the main high-affinity
      Pi transceptor in Saccharomyces cerevisiae Although transport mechanisms have
      been suggested for other MFS members, the key residues and molecular events
      driving transport by Pi:H+ symporters are unclear. The current Pho84 transport
      model is based on the inward-facing occluded crystal structure of the Pho84
      homologue PiPT in the fungus Piriformospora indica However, this model is limited
      by the lack of experimental data on the regulatory residues for each stage of the
      transport cycle. In this study, an open, inward-facing conformation of Pho84 was
      used to study the release of Pi A comparison of this conformation with the model
      for Pi release in PiPT revealed that Tyr179 in Pho84 (Tyr150 in PiPT) is not part
      of the Pi binding site. This difference may be due to a lack of detailed
      information on the Pi release step in PiPT. Molecular dynamics simulations of
      Pho84 in which a residue adjacent to Tyr179, Asp178, is protonated revealed a
      conformational change in Pho84 from an open, inward-facing state to an occluded
      state. Tyr179 then became part of the binding site as was observed in the PiPT
      crystal structure. The importance of Tyr179 in regulating Pi release was
      supported by site-directed mutagenesis and transport assays. Using trehalase
      activity measurements, we demonstrated that the release of Pi is a critical step
      for transceptor signaling. Our results add to previous studies on PiPT, creating
      a more complete picture of the proton-coupled Pi transport cycle of a
      transceptor.

PMID- 27875296
TI  - The N-terminal Ankyrin Repeat Domain Is Not Required for Electrophile and Heat
      Activation of the Purified Mosquito TRPA1 Receptor.
AB  - Temperature sensors are crucial for animals to optimize living conditions. The
      temperature response of the ion channel transient receptor potential A1 (TRPA1)
      is intriguing; some orthologs have been reported to be activated by cold and
      others by heat, but the molecular mechanisms responsible for its activation
      remain elusive. Single-channel electrophysiological recordings of heterologously
      expressed and purified Anopheles gambiae TRPA1 (AgTRPA1), with and without the N
      terminal ankyrin repeat domain, demonstrate that both proteins are functional
      because they responded to the electrophilic compounds allyl isothiocyanate and
      cinnamaldehyde as well as heat. The proteins' similar intrinsic fluorescence
      properties and corresponding quenching when activated by allyl isothiocyanate or
      heat suggest lipid bilayer-independent conformational changes outside the N
      terminal domain. The results show that AgTRPA1 is an inherent thermo- and
      chemoreceptor, and analogous to what has been reported for the human TRPA1
      ortholog, the N-terminal domain may tune the response but is not required for the
      activation by these stimuli.

PMID- 27875297
TI  - Glycogen Synthase Kinase 3 (GSK-3)-mediated Phosphorylation of Uracil N
      Glycosylase 2 (UNG2) Facilitates the Repair of Floxuridine-induced DNA Lesions
      and Promotes Cell Survival.
AB  - Uracil N-glycosylase 2 (UNG2), the nuclear isoform of UNG, catalyzes the removal
      of uracil or 5-fluorouracil lesions that accumulate in DNA following treatment
      with the anticancer agents 5-fluorouracil and 5-fluorodeoxyuridine (floxuridine),
      a 5-fluorouracil metabolite. By repairing these DNA lesions before they can cause
      cell death, UNG2 promotes cancer cell survival and is therefore critically
      involved in tumor resistance to these agents. However, the mechanisms by which
      UNG2 is regulated remain unclear. Several phosphorylation sites within the N
      terminal regulatory domain of UNG2 have been identified, although the effects of
      these modifications on UNG2 function have not been fully explored, nor have the
      identities of the kinases involved been determined. Here we show that glycogen
      synthase kinase 3 (GSK-3) interacts with and phosphorylates UNG2 at Thr60 and
      that Thr60 phosphorylation requires a Ser64 priming phosphorylation event. We
      also show that mutating Thr60 or Ser64 to Ala increases the half-life of UNG2,
      reduces the rate of in vitro uracil excision, and slows UNG2 dissociation from
      chromatin after DNA replication. Using an UNG2-deficient ovarian cancer cell line
      that is hypersensitive to floxuridine, we show that GSK-3 phosphorylation
      facilitates UNG2-dependent repair of floxuridine-induced DNA lesions and promotes
      tumor cell survival following exposure to this agent. These data suggest that GSK
      3 regulates UNG2 and promotes DNA damage repair.

PMID- 27875298
TI  - Benzyl Isothiocyanate (BITC) Induces Reactive Oxygen Species-dependent Repression
      of STAT3 Protein by Down-regulation of Specificity Proteins in Pancreatic Cancer.
AB  - The antineoplastic agent benzyl isothiocyanate (BITC) acts by targeting multiple
      pro-oncogenic pathways/genes, including signal transducer and activator of
      transcription 3 (STAT3); however, the mechanism of action is not well known. As
      reported previously, BITC induced reactive oxygen species (ROS) in Panc1,
      MiaPaCa2, and L3.6pL pancreatic cancer cells. This was accompanied by induction
      of apoptosis and inhibition of cell growth and migration, and these responses
      were attenuated in cells cotreated with BITC plus glutathione (GSH). BITC also
      decreased expression of specificity proteins (Sp) Sp1, Sp3, and Sp4 transcription
      factors (TFs) and several pro-oncogenic Sp-regulated genes, including STAT3 and
      phospho-STAT3 (pSTAT3), and GSH attenuated these responses. Knockdown of Sp TFs
      by RNA interference also decreased STAT3/pSTAT3 expression. BITC-induced ROS
      activated a cascade of events that included down-regulation of c-Myc, and it was
      also demonstrated that c-Myc knockdown decreased expression of Sp TFs and STAT3
      These results demonstrate that in pancreatic cancer cells, STAT3 is an Sp
      regulated gene that can be targeted by BITC and other ROS inducers, thereby
      identifying a novel therapeutic approach for targeting STAT3.

PMID- 27875299
TI  - Lipids Cooperate with the Reovirus Membrane Penetration Peptide to Facilitate
      Particle Uncoating.
AB  - Virus-host interactions play a role in many stages of the viral lifecycle,
      including entry. Reovirus, a model system for studying the entry mechanisms of
      nonenveloped viruses, undergoes a series of regulated structural transitions that
      culminate in delivery of the viral genetic material. Lipids can trigger one of
      these conformational changes, infectious subviral particle (ISVP)-to-ISVP*
      conversion. ISVP* formation releases two virally encoded peptides, myristoylated
      MU1N (myr-MU1N) and Phi. Among these, myr-MU1N is sufficient to form pores within
      membranes. Released myr-MU1N can also promote ISVP* formation in trans Using
      thermal inactivation as a readout for ISVP-to-ISVP* conversion, we demonstrate
      that lipids render ISVPs less thermostable in a virus concentration-dependent
      manner. Under conditions in which neither lipids alone nor myr-MU1N alone
      promotes ISVP-to-ISVP* conversion, myr-MU1N induces particle uncoating when
      lipids are present. These data suggest that the pore-forming activity and the
      ISVP*-promoting activity of myr-MU1N are linked. Lipid-associated myr-MU1N
      interacts with ISVPs and triggers efficient ISVP* formation. The cooperativity
      between a reovirus component and lipids reveals a distinct virus-host interaction
      in which membranes can facilitate nonenveloped virus entry.

PMID- 27875300
TI  - The Fission Yeast Pre-mRNA-processing Factor 18 (prp18+) Has Intron-specific
      Splicing Functions with Links to G1-S Cell Cycle Progression.
AB  - The fission yeast genome, which contains numerous short introns, is an apt model
      for studies on fungal splicing mechanisms and splicing by intron definition. Here
      we perform a domain analysis of the evolutionarily conserved Schizosaccharomyces
      pombe pre-mRNA-processing factor, SpPrp18. Our mutational and biophysical
      analyses of the C-terminal alpha-helical bundle reveal critical roles for the
      conserved region as well as helix five. We generate a novel conditional missense
      mutant, spprp18-5 To assess the role of SpPrp18, we performed global splicing
      analyses on cells depleted of prp18+ and the conditional spprp18-5 mutant, which
      show widespread but intron-specific defects. In the absence of functional
      SpPrp18, primer extension analyses on a tfIId+ intron 1-containing minitranscript
      show accumulated pre-mRNA, whereas the lariat intron-exon 2 splicing intermediate
      was undetectable. These phenotypes also occurred in cells lacking both SpPrp18
      and SpDbr1 (lariat debranching enzyme), a genetic background suitable for
      detection of lariat RNAs. These data indicate a major precatalytic splicing
      arrest that is corroborated by the genetic interaction between spprp18-5 and
      spprp2-1, a mutant in the early acting U2AF59 protein. Interestingly, SpPrp18
      depletion caused cell cycle arrest before S phase. The compromised splicing of
      transcripts coding for G1-S regulators, such as Res2, a transcription factor, and
      Skp1, a regulated proteolysis factor, are shown. The cumulative effects of
      SpPrp18-dependent intron splicing partly explain the G1 arrest upon the loss of
      SpPrp18. Our study using conditional depletion of spprp18+ and the spprp18-5
      mutant uncovers an intron-specific splicing function and early spliceosomal
      interactions and suggests links with cell cycle progression.

PMID- 27875302
TI  - Proteasomal Degradation of the EWS-FLI1 Fusion Protein Is Regulated by a Single
      Lysine Residue.
AB  - E-26 transformation-specific (ETS) proteins are transcription factors directing
      gene expression through their conserved DNA binding domain. They are implicated
      as truncated forms or interchromosomal rearrangements in a variety of tumors
      including Ewing sarcoma, a pediatric tumor of the bone. Tumor cells express the
      chimeric oncoprotein EWS-FLI1 from a specific t(22;11)(q24;12) translocation. EWS
      FLI1 harbors a strong transactivation domain from EWSR1 and the DNA-binding ETS
      domain of FLI1 in the C-terminal part of the protein. Although Ewing cells are
      crucially dependent on continuous expression of EWS-FLI1, its regulation of
      turnover has not been characterized in detail. Here, we identify the EWS-FLI1
      protein as a substrate of the ubiquitin-proteasome system with a characteristic
      polyubiquitination pattern. Using a global protein stability approach, we
      determined the half-life of EWS-FLI1 to lie between 2 and 4 h, whereas full
      length EWSR1 and FLI1 were more stable. By mass spectrometry, we identified two
      ubiquitin acceptor lysine residues of which only mutation of Lys-380 in the ETS
      domain of the FLI1 part abolished EWS-FLI1 ubiquitination and stabilized the
      protein posttranslationally. Expression of this highly stable mutant protein in
      Ewing cells while simultaneously depleting the endogenous wild type protein
      differentially modulates two subgroups of target genes to be either EWS-FLI1
      protein-dependent or turnover-dependent. The majority of target genes are in an
      unaltered state and cannot be further activated. Our study provides novel
      insights into EWS-FLI1 turnover, a critical pathway in Ewing sarcoma
      pathogenesis, and lays new ground to develop novel therapeutic strategies in
      Ewing sarcoma.

PMID- 27875301
TI  - An Intrinsically Disordered APLF Links Ku, DNA-PKcs, and XRCC4-DNA Ligase IV in
      an Extended Flexible Non-homologous End Joining Complex.
AB  - DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in
      human cells is initiated by Ku heterodimer binding to a DSB, followed by
      recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic
      subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4).
      Ku also interacts with accessory factors such as aprataxin and polynucleotide
      kinase/phosphatase-like factor (APLF). Yet, how these factors interact to tether,
      process, and ligate DSB ends while allowing regulation and chromatin interactions
      remains enigmatic. Here, small angle X-ray scattering (SAXS) and mutational
      analyses show APLF is largely an intrinsically disordered protein that binds Ku,
      Ku/DNA-PKcs (DNA-PK), and X4L4 within an extended flexible NHEJ core complex.
      X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C
      terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with
      Ku, DNA-PK, and X4L4. Collective results unveil the solution architecture of the
      six-protein complex and suggest cooperative assembly of an extended flexible NHEJ
      core complex that supports APLF accessibility while possibly providing flexible
      attachment of the core complex to chromatin. The resulting dynamic tethering
      furthermore, provides geometric access of L4 catalytic domains to the DNA ends
      during ligation and of DNA-PKcs for targeted phosphorylation of other NHEJ
      proteins as well as trans-phosphorylation of DNA-PKcs on the opposing DSB without
      disrupting the core ligation complex. Overall the results shed light on
      evolutionary conservation of Ku, X4, and L4 activities, while explaining the
      observation that Ku80CTR and DNA-PKcs only occur in a subset of higher
      eukaryotes.

PMID- 27875304
TI  - Rapid Renal Regulation of Peroxisome Proliferator-activated Receptor gamma
      Coactivator-1alpha by Extracellular Signal-Regulated Kinase 1/2 in Physiological
      and Pathological Conditions.
AB  - Previous studies have shown that extracellular signal-regulated kinase 1/2
      (ERK1/2) directly inhibits mitochondrial function during cellular injury. We
      evaluated the role of ERK1/2 on the expression of peroxisome proliferator
      activated receptor gamma coactivator-1alpha (PGC-1alpha) gene, a master regulator
      of mitochondrial function. The potent and specific MEK1/2 inhibitor trametinib
      rapidly blocked ERK1/2 phosphorylation, decreased cytosolic and nuclear FOXO3a/1
      phosphorylation, and increased PGC-1alpha gene expression and its downstream
      mitochondrial biogenesis (MB) targets under physiological conditions in the
      kidney cortex and in primary renal cell cultures. The epidermal growth factor
      receptor (EGFR) inhibitor erlotinib blocked ERK1/2 phosphorylation and increased
      PGC-1alpha gene expression similar to treatment with trametinib, linking EGFR
      activation and FOXO3a/1 inactivation to the down-regulation of PGC-1alpha and MB
      through ERK1/2. Pretreatment with trametinib blocked early ERK1/2 phosphorylation
      following ischemia/reperfusion kidney injury and attenuated the down-regulation
      of PGC-1alpha and downstream target genes. These results demonstrate that ERK1/2
      rapidly regulates mitochondrial function through a novel pathway,
      EGFR/ERK1/2/FOXO3a/1/PGC-1alpha, under physiological and pathological conditions.
      As such, ERK1/2 down-regulates mitochondrial function directly by phosphorylation
      of upstream regulators of PGC-1alpha and subsequently decreasing MB.

PMID- 27875305
TI  - (-)-Englerin A-evoked Cytotoxicity Is Mediated by Na+ Influx and Counteracted by
      Na+/K+-ATPase.
AB  - (-)-Englerin A ((-)-EA) has a rapid and potent cytotoxic effect on several types
      of cancer cell that is mediated by plasma membrane ion channels containing
      transient receptor potential canonical 4 (TRPC4) protein. Because these channels
      are Ca2+-permeable, it was initially thought that the cytotoxicity arose as a
      consequence of Ca2+ overload. Here we show that this is not the case and that the
      effect of (-)-EA is mediated by a heteromer of TRPC4 and TRPC1 proteins. Both
      TRPC4 and TRPC1 were required for (-)-EA cytotoxicity; however, although TRPC4
      was necessary for the (-)-EA-evoked Ca2+ elevation, TRPC1 was not. TRPC1 either
      had no role or was a negative regulator of Ca2+ entry. By contrast, both TRPC4
      and TRPC1 were necessary for monovalent cation entry evoked by (-)-EA, and (-)-EA
      evoked cell death was dependent upon entry of the monovalent cation Na+ We
      therefore hypothesized that Na+/K+-ATPase might act protectively by counteracting
      the Na+ load resulting from sustained Na+ entry. Indeed, inhibition of Na+/K+
      ATPase by ouabain potently and strongly increased (-)-EA-evoked cytotoxicity. The
      data suggest that (-)-EA achieves cancer cell cytotoxicity by inducing sustained
      Na+ entry through heteromeric TRPC1/TRPC4 channels and that the cytotoxic effect
      of (-)-EA can be potentiated by Na+/K+-ATPase inhibition.

PMID- 27875306
TI  - Family-wide Structural Characterization and Genomic Comparisons Decode the
      Diversity-oriented Biosynthesis of Thalassospiramides by Marine Proteobacteria.
AB  - The thalassospiramide lipopeptides have great potential for therapeutic
      applications; however, their structural and functional diversity and biosynthesis
      are poorly understood. Here, by cultivating 130 Rhodospirillaceae strains sampled
      from oceans worldwide, we discovered 21 new thalassospiramide analogues and
      demonstrated their neuroprotective effects. To investigate the diversity of
      biosynthetic gene cluster (BGC) architectures, we sequenced the draft genomes of
      28 Rhodospirillaceae strains. Our family-wide genomic analysis revealed three
      types of dysfunctional BGCs and four functional BGCs whose architectures
      correspond to four production patterns. This correlation allowed us to reassess
      the "diversity-oriented biosynthesis" proposed for the microbial production of
      thalassospiramides, which involves iteration of several key modules. Preliminary
      evolutionary investigation suggested that the functional BGCs could have arisen
      through module/domain loss, whereas the dysfunctional BGCs arose through
      horizontal gene transfer. Further comparative genomics indicated that
      thalassospiramide production is likely to be attendant on particular
      genes/pathways for amino acid metabolism, signaling transduction, and compound
      efflux. Our findings provide a systematic understanding of thalassospiramide
      production and new insights into the underlying mechanism.

PMID- 27875307
TI  - Salmonella enteritidis Effector AvrA Stabilizes Intestinal Tight Junctions via
      the JNK Pathway.
AB  - Salmonella pathogenesis studies to date have focused on Salmonella typhimurium,
      and the pathogenesis of a second major serotype, Salmonella enteritidis, is
      poorly understood. Salmonella spp. possess effector proteins that display
      biochemical activities and modulate host functions. Here, we generated a deletion
      mutant of the effector AvrA, S.E-AvrA-, and a plasmid-mediated complementary
      strain, S.E-AvrA-/pAvrA+ (S.E-AvrA+), in S. Enteritidis. Using in vitro and in
      vivo infection models, we showed that AvrA stabilizes epithelial tight junction
      (TJ) proteins, such as ZO-1, in human intestinal epithelial cells.
      Transepithelial electrical resistance was significantly higher in cells infected
      with S.E-AvrA+ than in cells infected with S.E-AvrA- Inhibition of the JNK
      pathway suppresses the disassembly of TJ proteins; we found that enteritidis AvrA
      inhibited JNK activity in cells infected with wild type or S.E-AvrA+ strains.
      Therefore, Enteritidis AvrA-induced ZO-1 stability is achieved via suppression of
      the JNK pathway. Furthermore, the S.E-AvrA- strain led to enhanced bacterial
      invasion, both in vitro and in vivo Taken together, our data reveal a novel role
      for AvrA in S. Enteritidis: Enteritidis AvrA stabilizes intestinal TJs and
      attenuates bacterial invasion. The manipulation of JNK activity and TJs in
      microbial-epithelial interactions may be a novel therapeutic approach for the
      treatment of infectious diseases.

PMID- 27875308
TI  - Growth Phase-dependent Variation of RNase BN/Z Affects Small RNAs: REGULATION OF
      6S RNA.
AB  - RNase BN, the RNase Z family member in E. coli, can participate in the processing
      of tRNA precursors. However, this function only becomes apparent when other
      processing enzymes are absent, raising the question of its primary physiological
      role. Here, we show that RNase BN itself is subject to growth phase-dependent
      regulation, because both rbn mRNA and RNase BN protein are at their highest
      levels in early exponential phase, but then decrease dramatically and are
      essentially absent in stationary phase. As a consequence of this variation,
      certain small RNAs, such as 6S RNA, remain low in exponential phase cells, and
      increase greatly in stationary phase. RNase BN affects 6S RNA abundance by
      decreasing its stability in exponential phase. RNase BN levels increase rapidly
      as cells exit stationary phase and are primarily responsible for the decrease in
      6S RNA that accompanies this process. Purified RNase BN directly cleaves 6S RNA
      as shown by in vitro assays, and the 6S RNA:pRNA duplex is an even more favorable
      substrate of RNase BN. The exoribonuclease activity of RNase BN is unnecessary
      because all its action on 6S RNA is due to endonucleolytic cleavages. These data
      indicate that RNase BN plays an important role in determining levels of the
      global transcription regulator, 6S RNA, throughout the growth cycle.

PMID- 27875309
TI  - RNA Sequencing Reveals a Role of TonEBP Transcription Factor in Regulation of Pro
      inflammatory Genes in Response to Hyperosmolarity in Healthy Nucleus Pulposus
      Cells: A HOMEOSTATIC RESPONSE?
AB  - Transcription factor tonicity-responsive enhancer-binding protein (TonEBP/NFAT5)
      is critical for osmo-adaptation and extracellular matrix homeostasis of nucleus
      pulposus (NP) cells in their hypertonic tissue niche. Recent studies implicate
      TonEBP signaling in inflammatory disease and rheumatoid arthritis pathogenesis.
      However, broader functions of TonEBP in the disc remain unknown. RNA sequencing
      was performed on NP cells with TonEBP knockdown under hypertonic conditions. 1140
      TonEBP-dependent genes were identified and categorized using Ingenuity Pathway
      Analysis. Bioinformatic analysis showed enrichment of matrix homeostasis and
      cytokine/chemokine signaling pathways. C-C motif chemokine ligand 2 (CCL2),
      interleukin 6 (IL6), tumor necrosis factor (TNF), and nitric oxide synthase 2
      (NOS2) were studied further. Knockdown experiments showed that TonEBP was
      necessary to maintain expression levels of these genes. Gain- and loss-of
      function experiments and site-directed mutagenesis demonstrated that TonEBP
      binding to a specific site in the CCL2 promoter is required for hypertonic
      inducibility. Despite inhibition by dominant-negative TonEBP, IL6 and NOS2
      promoters were not hypertonicity-inducible. Whole-disc response to hypertonicity
      was studied in an ex vivo organ culture model, using wild-type and
      haploinsufficient TonEBP mice. Pro-inflammatory targets were induced by
      hypertonicity in discs from wild-type but not TonEBP-haploinsufficient mice.
      Mechanistically, NF-kappaB activity increased with hypertonicity and was
      necessary for hypertonic induction of target genes IL6, TNF, and NOS2 but not
      CCL2 Although TonEBP maintains transcription of genes traditionally considered
      pro-inflammatory, it is important to note that some of these genes also serve
      anabolic and pro-survival roles. Therefore, in NP cells, this phenomenon may
      reflect a physiological adaptation to diurnal osmotic loading of the
      intervertebral disc.

PMID- 27875311
TI  - Single Binding Mode Integration of Hemicellulose-degrading Enzymes via Adaptor
      Scaffoldins in Ruminococcus flavefaciens Cellulosome.
AB  - The assembly of one of Nature's most elaborate multienzyme complexes, the
      cellulosome, results from the binding of enzyme-borne dockerins to reiterated
      cohesin domains located in a non-catalytic primary scaffoldin. Generally,
      dockerins present two similar cohesin-binding interfaces that support a dual
      binding mode. The dynamic integration of enzymes in cellulosomes, afforded by the
      dual binding mode, is believed to incorporate additional flexibility in highly
      populated multienzyme complexes. Ruminococcus flavefaciens, the primary degrader
      of plant structural carbohydrates in the rumen of mammals, uses a portfolio of
      more than 220 different dockerins to assemble the most intricate cellulosome
      known to date. A sequence-based analysis organized R. flavefaciens dockerins into
      six groups. Strikingly, a subset of R. flavefaciens cellulosomal enzymes,
      comprising dockerins of groups 3 and 6, were shown to be indirectly incorporated
      into primary scaffoldins via an adaptor scaffoldin termed ScaC. Here, we report
      the crystal structure of a group 3 R. flavefaciens dockerin, Doc3, in complex
      with ScaC cohesin. Doc3 is unusual as it presents a large cohesin-interacting
      surface that lacks the structural symmetry required to support a dual binding
      mode. In addition, dockerins of groups 3 and 6, which bind exclusively to ScaC
      cohesin, display a conserved mechanism of protein recognition that is similar to
      Doc3. Groups 3 and 6 dockerins are predominantly appended to hemicellulose
      degrading enzymes. Thus, single binding mode dockerins interacting with adaptor
      scaffoldins exemplify an evolutionary pathway developed by R. flavefaciens to
      recruit hemicellulases to the sophisticated cellulosomes acting in the
      gastrointestinal tract of mammals.

PMID- 27875310
TI  - Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE
      STUDY.
AB  - Insulin, a protein critical for metabolic homeostasis, provides a classical model
      for protein design with application to human health. Recent efforts to improve
      its pharmaceutical formulation demonstrated that iodination of a conserved
      tyrosine (TyrB26) enhances key properties of a rapid-acting clinical analog.
      Moreover, the broad utility of halogens in medicinal chemistry has motivated the
      use of hybrid quantum- and molecular-mechanical methods to study proteins. Here,
      we (i) undertook quantitative atomistic simulations of 3-[iodo-TyrB26]insulin to
      predict its structural features, and (ii) tested these predictions by X-ray
      crystallography. Using an electrostatic model of the modified aromatic ring based
      on quantum chemistry, the calculations suggested that the analog, as a dimer and
      hexamer, exhibits subtle differences in aromatic-aromatic interactions at the
      dimer interface. Aromatic rings (TyrB16, PheB24, PheB25, 3-I-TyrB26, and their
      symmetry-related mates) at this interface adjust to enable packing of the
      hydrophobic iodine atoms within the core of each monomer. Strikingly, these
      features were observed in the crystal structure of a 3-[iodo-TyrB26]insulin
      analog (determined as an R6 zinc hexamer). Given that residues B24-B30 detach
      from the core on receptor binding, the environment of 3-I-TyrB26 in a receptor
      complex must differ from that in the free hormone. Based on the recent structure
      of a "micro-receptor" complex, we predict that 3-I-TyrB26 engages the receptor
      via directional halogen bonding and halogen-directed hydrogen bonding as follows:
      favorable electrostatic interactions exploiting, respectively, the halogen's
      electron-deficient sigma-hole and electronegative equatorial band. Inspired by
      quantum chemistry and molecular dynamics, such "halogen engineering" promises to
      extend principles of medicinal chemistry to proteins.

PMID- 27875312
TI  - Mutational Analysis of Atypical Chemokine Receptor 3 (ACKR3/CXCR7) Interaction
      with Its Chemokine Ligands CXCL11 and CXCL12.
AB  - Atypical chemokine receptors do not mediate chemotaxis or G protein signaling,
      but they recruit arrestin. They also efficiently scavenge their chemokine
      ligands, thereby contributing to gradient maintenance and termination. ACKR3,
      also known as CXCR7, binds and degrades the constitutive chemokine CXCL12, which
      also binds the canonical receptor CXCR4, and CXCL11, which also binds CXCR3. Here
      we report comprehensive mutational analysis of the ACKR3 interaction with its
      chemokine ligands, using 30 substitution mutants. Readouts are radioligand
      binding competition, arrestin recruitment, and chemokine scavenging. Our results
      suggest different binding modes for both chemokines. CXCL11 depends on the ACKR3
      N terminus and some extracellular loop (ECL) positions for primary binding, ECL
      residues mediate secondary binding and arrestin recruitment potency. CXCL12
      binding required key residues Asp-1794.60 and Asp-2756.58 (residue numbering
      follows the Ballesteros-Weinstein scheme), with no evident involvement of N
      terminal residues, suggesting an uncommon mode of receptor engagement. Mutation
      of residues corresponding to CRS2 in CXCR4 (positions Ser-1032.63 and Gln
      3017.39) increased CXCL11 binding, but reduced CXCL12 affinity. Mutant Q301E7.39
      did not recruit arrestin. Mutant K118A3.26 in ECL1 showed moderate baseline
      arrestin recruitment with ablation of ligand-induced responses. Substitutions
      that affected CXCL11 binding also diminished scavenging. However, detection of
      reduced CXCL12 scavenging by mutants with impaired CXCL12 affinity required
      drastically reduced receptor expression levels, suggesting that scavenging
      pathways can be saturated and that CXCL12 binding exceeds scavenging at higher
      receptor expression levels. Arrestin recruitment did not correlate with
      scavenging; although Q301E7.39 degraded chemokines in the absence of arrestin,
      S103D2.63 had reduced CXCL11 scavenging despite intact arrestin responses.

PMID- 27875313
TI  - Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic
      Biosynthesis in Streptomyces.
AB  - GlnR, an OmpR-like orphan two-component system response regulator, is a master
      regulator of nitrogen metabolism in the genus Streptomyces In this work, evidence
      that GlnR is also directly involved in the regulation of antibiotic biosynthesis
      is provided. In the model strain Streptomyces coelicolor M145, an in-frame
      deletion of glnR resulted in markedly increased actinorhodin (ACT) production but
      reduced undecylprodigiosin (RED) biosynthesis when exposed to R2YE culture
      medium. Transcriptional analysis coupled with DNA binding studies revealed that
      GlnR represses ACT but activates RED production directly via the pathway-specific
      activator genes actII-ORF4 and redZ, respectively. The precise GlnR-binding sites
      upstream of these two target genes were defined. In addition, the direct
      involvement of GlnR in antibiotic biosynthesis was further identified in
      Streptomyces avermitilis, which produces the important anthelmintic agent
      avermectin. We found that S. avermitilis GlnR (GlnRsav) could stimulate
      avermectin but repress oligomycin production directly through the respective
      pathway-specific activator genes, aveR and olmRI/RII To the best of our
      knowledge, this report describes the first experimental evidence demonstrating
      that GlnR regulates antibiotic biosynthesis directly through pathway-specific
      regulators in Streptomyces Our results suggest that GlnR-mediated regulation of
      antibiotic biosynthesis is likely to be universal in streptomycetes. These
      findings also indicate that GlnR is not only a master nitrogen regulator but also
      an important controller of secondary metabolism, which may help to balance
      nitrogen metabolism and antibiotic biosynthesis in streptomycetes.

PMID- 27875316
TI  - Coupling de novo protein folding with subunit exchange into pre-formed oligomeric
      protein complexes: the 'heritable template' hypothesis.
AB  - Despite remarkable advances in synthetic biology, the fact remains that it takes
      a living cell to make a new living cell. The information encoded in the genome is
      necessary to direct assembly of all cellular components, but it may not be
      sufficient. Some components (e.g. mitochondria) cannot be synthesized de novo,
      and instead require pre-existing templates, creating a fundamental continuity of
      life: if the template information is ever lost, the genomic code cannot suffice
      to ensure proper biogenesis. One type of information only incompletely encoded in
      the genome is the structures of macromolecular assemblies, which emerge from the
      conformations of the constituent molecules coupled with the ways in which these
      molecules interact. For many, if not most proteins, gene sequence is not the sole
      determinant of native conformation, particularly in the crowded cellular milieu.
      A partial solution to this problem lies in the functions of molecular chaperones,
      encoded by nearly all cellular genomes. Chaperones effectively restrict the
      ensemble of conformations sampled by polypeptides, promoting the acquisition of
      native, functional forms, but multiple proteins have evolved ways to achieve
      chaperone independence, perhaps by coupling folding with higher-order assembly.
      Here, I propose the existence of another solution: a novel mechanism of de novo
      folding in which the folding of specific proteins is templated by pre-folded
      molecules of a partner protein whose own folding also required similar
      templating. This hypothesis challenges prevailing paradigms by predicting that,
      in order to achieve a functional fold, some non-prion proteins require a seed
      passed down through generations.

PMID- 27875315
TI  - Lipid-tuned Zinc Transport Activity of Human ZnT8 Protein Correlates with Risk
      for Type-2 Diabetes.
AB  - Zinc is a critical element for insulin storage in the secretory granules of
      pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular
      sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single
      nonsynonymous nucleotide change contributes to increased susceptibility to type-2
      diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which
      is also a higher frequency (>50%) allele, is correlated with zinc transport
      activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8
      variant (Trp-325). The Arg-325 variant was found to be more active than the Trp
      325 form following induced expression in HEK293 cells. We further examined the
      functional consequences of changing lipid conditions to mimic the impact of lipid
      remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8
      variants in proteoliposomes exhibited more than 4-fold functional tunability by
      the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad
      range of permissive lipid compositions, the Arg-325 variant consistently
      exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement
      with the human genetic finding that rare loss-of-function mutations in ZnT8 are
      associated with reduced T2D risk, our results suggested that the common high risk
      Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce
      T2D risk in the general populations.

PMID- 27875317
TI  - CYP2D6 variability in populations from Venezuela.
AB  - CYP2D6 is an important cytochrome P450 enzyme that plays an important role in the
      metabolism of about 25% of currently prescribed drugs. The presence of
      polymorphisms in the CYP2D6 gene may modulate enzyme level and activity, thereby
      affecting individual responses to pharmacological treatments. The most prevalent
      diseases in the admixed population from Venezuela are cardiovascular and cancer,
      whereas viral, bacterial and parasitic diseases, particularly malaria, are
      prevalent in Amerindian populations; in the treatment of these diseases, several
      drugs that are metabolized by CYP2D6 are used. In this work, we reviewed the data
      on CYP2D6 variability and predicted metabolizer phenotypes, in healthy volunteers
      of two admixed and five Amerindian populations from Venezuela. The Venezuelan
      population is very heterogeneous as a result of the genetic admixture of three
      major ethnical components: Europeans, Africans and Amerindians. There are
      noticeable inter-regional and inter-population differences in the process of
      mixing of this population. Hitherto, there are few published studies in Venezuela
      on CYP2D6; therefore, it is necessary to increase research in this regard, in
      particular to develop studies with a larger sample size. There is a considerable
      amount of work remaining before CYP2D6 is integrated into clinical practice in
      Venezuela.

PMID- 27875314
TI  - Receptor MER Tyrosine Kinase Proto-oncogene (MERTK) Is Not Required for Transfer
      of Bis-retinoids to the Retinal Pigmented Epithelium.
AB  - Accumulation of bis-retinoids in the retinal pigmented epithelium (RPE) is a
      hallmark of aging and retinal disorders such as Stargardt disease and age-related
      macular degeneration. These aberrant fluorescent condensation products, including
      di-retinoid-pyridinium-ethanolamine (A2E), are thought to be transferred to RPE
      cells primarily through phagocytosis of the photoreceptor outer segments.
      However, we observed by two-photon microscopy that mouse retinas incapable of
      phagocytosis due to a deficiency of the c-Mer proto-oncogene tyrosine kinase
      (Mertk) nonetheless contained fluorescent retinoid condensation material in their
      RPE. Primary RPE cells from Mertk-/- mice also accumulated fluorescent products
      in vitro Finally, quantification of A2E demonstrated the acquisition of retinal
      condensation products in Mertk-/- mouse RPE prior to retinal degeneration. In
      these mice, we identified activated microglial cells that likely were recruited
      to transport A2E-like condensation products to the RPE and dispose of the dying
      photoreceptor cells. These observations demonstrate a novel transport mechanism
      between photoreceptor cells and RPE that does not involve canonical Mertk
      dependent phagocytosis.

PMID- 27875318
TI  - 1846G>A polymorphism of CYP2D6 gene and extrapyramidal side effects during
      antipsychotic therapy among Russians and Tatars: a pilot study.
AB  - BACKGROUND: Sytochrome P450 CYP2D6 activity affects antipsychotic therapy safety.
      1846G>A (CYP2D6*4) polymorphism frequency varies among different ethnic groups.
      METHODS: We studied 1846G>A polymorphism in Tatar and Russian schizophrenic
      patients taking different antipsychotics and association of 1846G>A polymorphism
      and extrapyramidal disorders (EPD) frequency in schizophrenic patients on
      haloperidol monotherapy in daily doses up to 20 mg. RESULTS: Heterozygous 1846GA
      genotype frequency among Tatars was lower (23.8% vs. 32.4% in Russians), but the
      differences did not reach statistical significance. The 1846A allele frequency
      among Tatars was also lower (11.9% vs. 24.3% in Russians), but the difference was
      not quite significant (p=0.0592). Average daily haloperidol dose in the group
      without EPD was significantly higher than in the group with EPD (11.35+/-4.6 vs.
      13.87+/-3.3 mg, p=0.0252), but average daily haloperidol dose/weight ratios in
      the compared groups had no significant differences. A statistically significant
      association between EPD development and heterozygous 1846GA genotype and 1846A
      allele carrier frequency was revealed among all schizophrenic patients and among
      those of Tatars. CONCLUSIONS: Further well-designed pharmacogenetic studies in
      different Russian regions are needed to improve psychotropic therapy safety and
      to establish evidence-based indications for pharmacogenetic testing in clinical
      practice.

PMID- 27875319
TI  - Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in
      male Wistar rats: involvement of CYP2D6 inhibition.
AB  - BACKGROUND: Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function
      oxidase system, is an important CYP isoform with regard to herbal-drug
      interactions and is responsible for the metabolism of nearly 25% of drugs. Until
      now, studies on the effects of various phytochemicals on CYP2D6 activity in vivo
      have been very rare. Gallic acid and ellagic acid are natural polyphenols which
      are widely distributed in fruits and medicinal plants. In the present study, the
      effects of gallic acid and ellagic acid pretreatment on intestinal transport and
      oral bioavailability of metoprolol were investigated. METHODS: The intestinal
      transport of metoprolol was assessed by conducting an in situ single pass
      intestinal perfusion (SPIP) study. The bioavailability study was conducted to
      evaluate the pharmacokinetic parameters of orally administered metoprolol in
      rats. RESULTS: After pretreatment with gallic acid and ellagic acid, no
      significant change in effective permeability of metoprolol was observed at the
      ileum part of rat intestine. A significant improvement in the peak plasma
      concentration (Cmax) and area under the serum concentration-time profile (AUC)
      and decrease in clearance were observed in rats pretreated with gallic acid and
      ellagic acid. CONCLUSIONS: Gallic acid and ellagic acid significantly enhanced
      the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism
      in the rat liver. Hence, adverse herbal-drug interactions may result with
      concomitant ingestion of gallic acid and ellagic acid supplements and drugs that
      are CYP2D6 substrates. The clinical assessment of these interactions should be
      further investigated in human volunteers.

PMID- 27875320
TI  - Association of chronic hepatitis B virus infection with preterm birth: our
      experience and meta-analysis.
AB  - OBJECTIVES: To assess the association of chronic hepatitis B virus (HBV)
      infection with preterm birth (PTB). METHODS: A cohort of 20,498 pregnant women
      (497 HBV carriers with 20,001 non-HBV controls) with normal alanine
      aminotransferase (ALT) levels was selected from the Obstetrics & Gynecology
      Hospital of Nantong University. The clinical parameters and PTB incidence were
      compared between HBV carriers and non-HBV subjects. For the meta-analysis, we
      searched the PubMed, Ovid and Cochrane Library databases for studies comparing
      PTB incidence between individuals with chronic HBV infection and non-HBV
      subjects. RESULTS: HBV carriers were slightly older and had slightly higher ALT
      levels within normal limits. The body mass index, education and history of
      pregnancy between HBV carrier and non-HBV groups were comparable. PTB incidence
      was not associated with HBV carrier status [relative risk (RR) 0.98, 95%
      confidence interval (CI) 0.71-1.37] in our cohort. However, the meta-analysis
      involving eight published studies and our study revealed a significant
      association between chronic HBV infection and PTB incidence (pooled RR 1.26, 95%
      CI 1.19-1.33). CONCLUSION: While maternal HBV carriers did not have a higher
      incidence of PTB in our cohort, the meta-analysis indicates that individuals with
      chronic HBV infection appeared to be at risk of PTB as a whole.

PMID- 27875321
TI  - The impact of selected environmental, behavioral and psychosocial factors on
      schoolchildren's somatic and mental health.
AB  - Children develop rapidly and many exogenous determinants of health significantly
      affect their somatic and mental development. There is a subjective perception of
      cognitive load associated with the educational process. The aim of the study is
      to assess individual environmental, behavioral and psychosocial factors
      influencing physical health and to investigate the amount of mental load in
      children. We investigated 87 schoolchildren (47 girls and 40 boys) aged 10-12
      years, who were attending primary school in Bratislava. To assess values of
      selected factors we used a questionnaire form and personality characteristics
      were estimated by standardized psycho-diagnostic and IQ tests [range of classic
      fear, social-situation anxiety and jitters [skala Klasickeho strachu a Socialno
      situacnej (in Slovak)] (KSAT), Eyesenck Personality Questionnaire for children
      (EPQ), Raven's IQ test]. Self-reported perception of mental load was assessed by
      questionnaire of subjective feelings and states (SFS). Children's body parameters
      were assessed using anthropometric measurements [height, weight, chest, abdominal
      and hip girth, Rohrer's index (RI), body mass index (BMI)] and a body fat
      measurement method (skinfold thickness). The results confirmed a significant
      relationship between higher parameters of overweight and obesity and irregular
      breakfast eating (p<0.05), absence of family dining (p<0.05), exposure to tobacco
      smoke in the family environment (p<0.01) and mother's level of education
      (p<0.05). Almost 60% of children reported high mental effort and cognitive load
      associated with the educational process. We note a close relationship between the
      higher mental load and the score of neuroticism (p<0.01). The physical and mental
      health of schoolchildren is significantly affected by exogenous factors.
      Therefore, in terms of protection and promotion of children's health, it is
      important to evaluate and monitor environmental risk factors and to form their
      healthy habits.

PMID- 27875322
TI  - Tree-based quantitative trait mapping in the presence of external covariates.
AB  - A central goal in biological and biomedical sciences is to identify the molecular
      basis of variation in morphological and behavioral traits. Over the last decade,
      improvements in sequencing technologies coupled with the active development of
      association mapping methods have made it possible to link single nucleotide
      polymorphisms (SNPs) and quantitative traits. However, a major limitation of
      existing methods is that they are often unable to consider complex, but
      biologically-realistic, scenarios. Previous work showed that association mapping
      method performance can be improved by using the evolutionary history within each
      SNP to estimate the covariance structure among randomly-sampled individuals.
      Here, we propose a method that can be used to analyze a variety of data types,
      such as data including external covariates, while considering the evolutionary
      history among SNPs, providing an advantage over existing methods. Existing
      methods either do so at a computational cost, or fail to model these
      relationships altogether. By considering the broad-scale relationships among
      SNPs, the proposed approach is both computationally-feasible and informed by the
      evolutionary history among SNPs. We show that incorporating an approximate
      covariance structure during analysis of complex data sets increases performance
      in quantitative trait mapping, and apply the proposed method to deer mice data.

PMID- 27875323
TI  - Estimating intrinsic and extrinsic noise from single-cell gene expression
      measurements.
AB  - Gene expression is stochastic and displays variation ("noise") both within and
      between cells. Intracellular (intrinsic) variance can be distinguished from
      extracellular (extrinsic) variance by applying the law of total variance to data
      from two-reporter assays that probe expression of identically regulated gene
      pairs in single cells. We examine established formulas [Elowitz, M. B., A. J.
      Levine, E. D. Siggia and P. S. Swain (2002): "Stochastic gene expression in a
      single cell," Science, 297, 1183-1186.] for the estimation of intrinsic and
      extrinsic noise and provide interpretations of them in terms of a hierarchical
      model. This allows us to derive alternative estimators that minimize bias or mean
      squared error. We provide a geometric interpretation of these results that
      clarifies the interpretation in [Elowitz, M. B., A. J. Levine, E. D. Siggia and
      P. S. Swain (2002): "Stochastic gene expression in a single cell," Science, 297,
      1183-1186.]. We also demonstrate through simulation and re-analysis of published
      data that the distribution assumptions underlying the hierarchical model have to
      be satisfied for the estimators to produce sensible results, which highlights the
      importance of normalization.

PMID- 27875324
TI  - Adaptive input data transformation for improved network reconstruction with
      information theoretic algorithms.
AB  - We propose a novel systematic procedure of non-linear data transformation for an
      adaptive algorithm in the context of network reverse-engineering using
      information theoretic methods. Our methodology is rooted in elucidating and
      correcting for the specific biases in the estimation techniques for mutual
      information (MI) given a finite sample of data. These are, in turn, tied to lack
      of well-defined bounds for numerical estimation of MI for continuous probability
      distributions from finite data. The nature and properties of the inevitable bias
      is described, complemented by several examples illustrating their form and
      variation. We propose an adaptive partitioning scheme for MI estimation that
      effectively transforms the sample data using parameters determined from its local
      and global distribution guaranteeing a more robust and reliable reconstruction
      algorithm. Together with a normalized measure (Shared Information Metric) we
      report considerably enhanced performance both for in silico and real-world
      biological networks. We also find that the recovery of true interactions is in
      particular better for intermediate range of false positive rates, suggesting that
      our algorithm is less vulnerable to spurious signals of association.

PMID- 27875325
TI  - Phase diagram of interacting spinless fermions on the honeycomb lattice.
AB  - Fermions hopping on a hexagonal lattice represent one of the most active research
      fields in condensed matter since the discovery of graphene in 2004 and its
      numerous applications. Another exciting aspect of the interplay between geometry
      and quantum mechanical effects is given by the Haldane model (Haldane 1988 Phys.
      Rev. Lett. 61 2015), where spinless fermions experiencing a certain flux pattern
      on the honeycomb lattice leads to the stabilization of a topological phase of
      matter, distinct from a Mott insulator and nowadays dubbed Chern insulator. In
      this context, it is crucial to understand the role of interactions and this
      review will describe recent results that have been obtained for a minimal model,
      namely spinless fermions with nearest and next-nearest neighbour density-density
      interactions on the honeycomb lattice at half-filling. Topics addressed include
      an introduction of the minimal model and a discussion of the possible
      instabilities of the Dirac semimetal, a presentation of various theoretical and
      numerical approaches, and a summary of the results with a particular emphasis on
      the stability or not of some exotic quantum phases such as charge ordered ones
      (similar to Wigner crystals) and spontaneous Chern insulator phases.

PMID- 27875326
TI  - Modeling hybrid perovskites by molecular dynamics.
AB  - The topical review describes the recent progress in the modeling of hybrid
      perovskites by molecular dynamics simulations. Hybrid perovskites and in
      particular methylammonium lead halide (MAPI) have a tremendous technological
      relevance representing the fastest-advancing solar material to date. They also
      represent the paradigm of an organic-inorganic crystalline material with some
      conceptual peculiarities: an inorganic semiconductor for what concerns the
      electronic and absorption properties with a hybrid and solution processable
      organic-inorganic body. After briefly explaining the basic concepts of ab initio
      and classical molecular dynamics, the model potential recently developed for
      hybrid perovskites is described together with its physical motivation as a simple
      ionic model able to reproduce the main dynamical properties of the material.
      Advantages and limits of the two strategies (either ab initio or classical) are
      discussed in comparison with the time and length scales (from pico to microsecond
      scale) necessary to comprehensively study the relevant properties of hybrid
      perovskites from molecular reorientations to electrocaloric effects. The state-of
      the-art of the molecular dynamics modeling of hybrid perovskites is reviewed by
      focusing on a selection of showcase applications of methylammonium lead halide:
      molecular cations disorder; temperature evolution of vibrations; thermally
      activated defects diffusion; thermal transport. We finally discuss the
      perspectives in the modeling of hybrid perovskites by molecular dynamics.

PMID- 27875327
TI  - Automated tracking of colloidal clusters with sub-pixel accuracy and precision.
AB  - Quantitative tracking of features from video images is a basic technique employed
      in many areas of science. Here, we present a method for the tracking of features
      that partially overlap, in order to be able to track so-called colloidal
      molecules. Our approach implements two improvements into existing particle
      tracking algorithms. Firstly, we use the history of previously identified feature
      locations to successfully find their positions in consecutive frames. Secondly,
      we present a framework for non-linear least-squares fitting to summed radial
      model functions and analyze the accuracy (bias) and precision (random error) of
      the method on artificial data. We find that our tracking algorithm correctly
      identifies overlapping features with an accuracy below 0.2% of the feature radius
      and a precision of 0.1 to 0.01 pixels for a typical image of a colloidal cluster.
      Finally, we use our method to extract the three-dimensional diffusion tensor from
      the Brownian motion of colloidal dimers.

PMID- 27875328
TI  - Ca- and Sc-based ternary AlB2-like crystals: a first-principles study.
AB  - The aluminum diboride (AlB2) crystal structure comprises intercalated metal atoms
      between honeycomb sheets. In addition to metal diborides, which represent the
      most common family of AlB2-like structures, many more materials are known to
      crystallize in this geometry. Here we use first-principles calculations to probe
      the structural and electronic properties of several such systems. Specifically,
      we investigate the stability of various polymorphs of CaAuAs, CaAuP, CaCuP,
      ScAuGe, ScAuSi, Ca2AgSi3 and Ca2AuGe3 and find lattice parameters in excellent
      agreement with available experimental data. The analysis of densities of states
      and band structure diagrams show that all materials are metallic. However, the
      details of band dispersion vary significantly, from typical metals such as CaAuP,
      to almost semi-metallic behaviour in CaCuP.

PMID- 27875329
TI  - Classical and quantum many-body effects on the critical properties and
      thermodynamic regularities of silicon.
AB  - Using molecular simulation, we determine the critical properties of Si as well as
      the loci for several remarkable thermodynamic contours spanning the supercritical
      region of the phase diagram. We consider a classical three-body potential as well
      as a quantum (tight-binding) many-body model, and determine the loci for the
      ideality contours, including the Zeno line and the H line of ideal enthalpy. The
      two strategies (classical or quantum) lead to strongly asymmetric binodals and to
      critical properties in good agreement with each other. The Zeno and H lines are
      found to remain linear over a wide temperature interval, despite the changes in
      electronic structure undergone by the fluid along these contours. We also show
      that the classical and quantum model yield markedly different results for the
      parameters defining the H line, the exponents for the power-laws underlying the
      line of minima for the isothermal enthalpy and for the density required to
      achieve ideal behavior, most notably for the enthalpy.

PMID- 27875330
TI  - Synthesis and properties of ultra-long InP nanowires on glass.
AB  - We report on the synthesis of Au-catalyzed InP nanowires (NWs) on low-cost glass
      substrates. Ultra-dense and ultra-long (up to ~250 MUm) InP NWs, with an
      exceptionally high growth rate of ~25 MUm min-1, were grown directly on glass
      using metal organic vapor phase epitaxy (MOVPE). Structural properties of InP NWs
      grown on glass were similar to the ones grown typically on Si substrates showing
      many structural twin faults but the NWs on glass always exhibited a stronger
      photoluminescence (PL) intensity at room temperature. The PL measurements of NWs
      grown on glass reveal two additional prominent impurity related emission peaks at
      low temperature (10 K). In particular, the strongest unusual emission peak with
      an activation energy of 23.8 +/- 2 meV was observed at 928 nm. Different
      possibilities including the role of native defects (phosphorus and/or indium
      vacancies) are discussed but most likely the origin of this PL peak is related to
      the impurity incorporation from the glass substrate. Furthermore, despite the
      presence of suspected impurities, the NWs on glass show outstanding light
      absorption in a wide spectral range (60%-95% for lambda = 300-1600 nm). The
      optical properties and the NW growth mechanism on glass is discussed
      qualitatively. We attribute the exceptionally high growth rate mostly to the
      atmospheric pressure growth conditions of our MOVPE reactor and stronger PL
      intensity on glass due to the impurity doping. Overall, the III-V NWs grown on
      glass are similar to the ones grown on semiconductor substrates but offer
      additional advantages such as low-cost and light transparency.

PMID- 27875331
TI  - Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery
      system for curcumin bioavailability enhancement.
AB  - In the present work, a simple method was used to develop composite curcumin-amine
      functionalized mesoporous silica nanoparticles (MSN). The nanoparticles were used
      to improve the bioavailability of curcumin in mice through oral administration.
      We investigated the effect of particle size on the release profile, solubility
      and oral bioavailability of curcumin in mice, including amine functionalized
      mesoporous silica micron-sized-particles (MSM) and MSN (100-200 nm). Curcumin
      loaded within amine functionalized MSN (MSN-A-Cur) had a better release profile
      and a higher solubility compared to amine MSM (MSM-A-Cur). The bioavailability of
      MSN-A-Cur and MSM-A-Cur was considerably higher than that of 'free curcumin'.
      These results indicate promising features of amine functionalized MSN as a
      carrier to deliver low solubility drugs with improved bioavailability via the
      oral route.

PMID- 27875332
TI  - Local electronic structure and nanolevel hierarchical organization of bone
      tissue: theory and NEXAFS study.
AB  - Theoretical and experimental investigations of native bone are carried out to
      understand relationships between its hierarchical organization and local
      electronic and atomic structure of the mineralized phase. The 3D superlattice
      model of a coplanar assembly of the hydroxyapatite (HAP) nanocrystallites
      separated by the hydrated nanolayers is introduced to account the interplay of
      short-, long- and super-range order parameters in bone tissue. The model is
      applied to (i) predict and rationalize the HAP-to-bone spectral changes in the
      electronic structure and (ii) describe the mechanisms ensuring the link of the
      hierarchical organization with the electronic structure of the mineralized phase
      in bone. To check the predictions the near-edge x-ray absorption fine structure
      (NEXAFS) at the Ca 2p, P 2p and O 1s thresholds is measured for native bone and
      compared with NEXAFS for reference compounds. The NEXAFS analysis has
      demonstrated the essential hierarchy induced HAP-to-bone red shifts of the Ca and
      P 2p-to-valence transitions. The lowest O 1s excitation line at 532.2 eV in bone
      is assigned with superposition of core transitions in the hydroxide OH-(H2O) m
      anions, Ca2+(H2O) n cations, the carboxyl groups inside the collagen and [PO4]2-
      and [PO4]- anions with unsaturated P-O bonds.

PMID- 27875333
TI  - NaSrMn2F7, NaCaFe2F7, and NaSrFe2F7: novel single crystal pyrochlore
      antiferromagnets.
AB  - The crystal structures and magnetic properties of three previously unreported
      A2B2F7 pyrochlore materials, NaSrMn2F7, NaCaFe2F7, and NaSrFe2F7 are presented.
      In these compounds, either S  =  2Fe2+ or S  =  5/2Mn2+ is on the B site, while
      nonmagnetic Na and Ca (Na and Sr) are disordered on the A site. The materials,
      which were grown as crystals via the floating zone method, display high effective
      magnetic moments and large Curie-Weiss thetas. Despite these characteristics, no
      ordering transition is detected. However, freezing of the magnetic spins,
      characterized by peaks in the susceptibility or specific heat, is observed at
      very low temperatures. The empirical frustration index, f  =  -theta CW/T f, for
      the materials are 36 (NaSrMn2F7), 27 (NaSrFe2F7), and 19 (NaCaFe2F7). AC
      susceptibility, DC susceptibility, and heat capacity measurements are used to
      characterize the observed spin glass behavior. The results suggest that the
      compounds are frustrated pyrochlore antiferromagnets with weak bond disorder. The
      magnetic phenomena that these fluoride pyrochlores exhibit, in addition to their
      availability as relatively large single crystals, make them promising candidates
      for the study of geometric magnetic frustration.

PMID- 27875334
TI  - Thin film growth studies using time-resolved x-ray scattering.
AB  - Thin-film growth is important for novel functional materials and new generations
      of devices. The non-equilibrium growth physics involved is very challenging,
      because the energy landscape for atomic scale processes is determined by many
      parameters, such as the diffusion and Ehrlich-Schwoebel barriers. We review the
      in situ real-time techniques of x-ray diffraction (XRD), x-ray growth
      oscillations and diffuse x-ray scattering (GISAXS) for the determination of
      structure and morphology on length scales from A to um. We give examples of time
      resolved growth experiments mainly from molecular thin film growth, but also
      highlight growth of inorganic materials using molecular beam epitaxy (MBE) and
      electrochemical deposition from liquids. We discuss how scaling parameters of
      rate equation models and fundamental energy barriers in kinetic Monte Carlo
      methods can be determined from fits of the real-time x-ray data.

PMID- 27875335
TI  - Flame-made ultra-porous TiO2 layers for perovskite solar cells.
AB  - We report methyl ammonium lead iodide (MAPbI3) solar cells with an ultra-porous
      TiO2 electron transport layer fabricated using sequential flame aerosol and
      atomic layer depositions of porous and compact TiO2 layers. Flame aerosol
      pyrolysis allows rapid deposition of nanostructured and ultra-porous TiO2 layers
      that could be easily scaled-up for high-throughput low-cost industrial solar cell
      production. An efficiency of 13.7% was achieved with a flame-made nanostructured
      and ultra-porous TiO2 electrode that was coated with a compact 2 nm TiO2 layer.
      This demonstrates that MAPbI3 solar cells with a flame-made porous TiO2 layer can
      have a comparable efficiency to that of the control MAPbI3 solar cell with the
      well-established spin-coated porous TiO2 layer. The combination of flame aerosol
      and atomic layer deposition provides precise control of the TiO2 porosity.
      Notably, the porosity of the as-deposited flame-made TiO2 layers was 97% which
      was then fine-tuned down to 87%, 56% and 35% by varying the thickness of the
      subsequent compact TiO2 coating step. The effects of the decrease in porosity on
      the device performance are discussed. It is also shown that MAPbI3 easily
      infiltrates into the flame-made porous TiO2 nanostructure thanks to their high
      porosity and large pore size.

PMID- 27875336
TI  - Synthesis of carbon nanofibers by CVD as a catalyst support material using
      atomically ordered Ni3C nanoparticles.
AB  - Atomically ordered nickel carbide (Ni3C) nanoparticles in polygonal shapes were
      prepared through the reduction of nickelocene. A novel type of carbon nanofiber
      (CNF) with twisted conformation was synthesized successfully by catalytic
      chemical vapor deposition (CCVD) using the obtained Ni3C nanoparticles at a
      relatively low temperature of 350  degrees C, which is below the lower limit
      temperature of 400  degrees C for the growth of CNFs using metal catalysts. The
      growth mechanism of the twisted CNFs from Ni3C was freshly derived based on the
      detailed characterizations. Compared with the growth of CNFs from Ni, graphene
      layers nucleate at monoatomic step edges and grow in a layer-by-layer manner,
      while the rotation of the polygonal Ni3C nanoparticles fabricates the twisted
      conformation during the CNF growth. The electrochemical activity and performance
      of the twisted CNFs loaded with Pt as electrode catalysts for a polymer
      electrolyte membrane fuel cell (PEMFC) were measured to be better than those of
      straight CNFs grown from Ni nanoparticles at 500  degrees C, since the specific
      surface conformation helps to make the loaded Pt more homogeneous.

PMID- 27875337
TI  - Low-cost superior solid-state symmetric supercapacitors based on hematite
      nanocrystals.
AB  - We present a facile method for the fabrication of hematite nanocrystal-carbon
      cloth (Fe2O3-CC) composite. Hierarchical manganite is chosen as the sacrificial
      precursor, that does not contribute to the component of final iron oxide but can
      be in situ dissolved by the acid produced from the Fe3+ hydrolysis. This method
      effectively enhances the specific surface area and conductivity of hematite
      (Fe2O3) by attaching Fe2O3 nanocrystals (around 5 nm) firmly on the surface of
      carbon fibers. The obtained Fe2O3-CC can be directly used as a binder-free
      electrode for a supercapacitor. Interestingly, the composite electrode exhibits
      synergistic electrochemical capacitance (electrochemical double-layer capacitance
      and pseudo-capacitance). It manifests a very high areal capacitance of 1.66 F cm
      2 (1660 F g-1) at 2 mA cm-2 and excellent cycling performance at large current
      densities (88.6% retention at 30 mA cm-2 after 5000 cycles) in a three-electrode
      testing system, which is among the best performances reported in the literature.
      Importantly, when fabricated as a solid-state flexible symmetric supercapacitor
      it still shows a maximum energy density of 8.74 mW h cm-3 and power density of
      253.9 mW cm-3. Additionally, its good flexibility makes it suitable for portable
      devices.

PMID- 27875339
TI  - Apolipoprotein CIII is a new player in diabetes.
AB  - PURPOSE OF REVIEW: Type-1 and type-2 diabetes are diseases with an increasing
      number of patients and a complex, multifactorial pathogenesis. Apolipoprotein
      (apo) CIII is increased in both types of diabetes and interventions preventing
      the increase have effects on the development of diabetes. RECENT FINDINGS:
      ApoCIII affects intracellular Ca-handling by activating voltage-gated Ca
      channels. ApoCIII is produced within the pancreatic islets and it increases in
      parallel with the development of insulin resistance and type-2 diabetes.
      Preventing the increase maintains a normal glucose tolerance as well as Ca
      handling and no signs of inflammation can be seen in islets wherein the augmented
      local production of the apolipoprotein is absent. SUMMARY: ApoCIII has been found
      to interfere with both function and survival of the beta-cell and thereby promote
      the development of diabetes. Increased levels of this apolipoprotein affects
      intracellular Ca-handling and insulin sensitivity, which finally results in
      impaired glucose homeostasis and diabetes. Interestingly, in a type-1 diabetes
      rat model lowering of apoCIII delays onset of diabetes. In type-2 diabetes
      insulin resistance within the pancreatic islets leads to a local increase in
      apoCIII that promotes inflammation and beta-cell dysfunction. Hence, targeting
      apoCIII may constitute a novel pharmacological strategy to treat both type-1 and
      type-2 diabetes.

PMID- 27875338
TI  - An Image-Domain Contrast Material Extraction Method for Dual-Energy Computed
      Tomography.
AB  - OBJECTIVES: Conventional material decomposition techniques for dual-energy
      computed tomography (CT) assume mass or volume conservation, where the CT number
      of each voxel is fully assigned to predefined materials. We present an image
      domain contrast material extraction process (CMEP) method that preferentially
      extracts contrast-producing materials while leaving the remaining image intact.
      MATERIALS AND METHODS: Image processing freeware (Fiji) is used to perform
      consecutive arithmetic operations on a dual-energy ratio map to generate masks,
      which are then applied to the original images to generate material-specific
      images. First, a low-energy image is divided by a high-energy image to generate a
      ratio map. The ratio map is then split into material-specific masks. Ratio
      intervals known to correspond to particular materials (eg, iodine, calcium) are
      assigned a multiplier of 1, whereas ratio values in between these intervals are
      assigned linear gradients from 0 to 1. The masks are then multiplied by an
      original CT image to produce material-specific images. The method was tested
      quantitatively at dual-source CT and rapid kVp-switching CT (RSCT) with phantoms
      using pure and mixed formulations of tungsten, calcium, and iodine. Errors were
      evaluated by comparing the known material concentrations with those derived from
      the CMEP material-specific images. Further qualitative evaluation was performed
      in vivo at RSCT with a rabbit model using identical CMEP parameters to the
      phantom. Orally administered tungsten, vascularly administered iodine, and
      skeletal calcium were used as the 3 contrast materials. RESULTS: All 5 material
      combinations-tungsten, iodine, and calcium, and mixtures of tungsten-calcium and
      iodine-calcium-showed distinct dual-energy ratios, largely independent of
      material concentration at both dual-source CT and RSCT. The CMEP was successful
      in both phantoms and in vivo. For pure contrast materials in the phantom, the
      maximum error between the known and CMEP-derived material concentrations was 0.9
      mg/mL, 24.9 mg/mL, and 0.4 mg/mL for iodine, calcium, and tungsten respectively.
      Mixtures of iodine and calcium showed the highest discrepancies, which reflected
      the sensitivity of iodine to the image-type chosen for the extraction of the
      final material-specific image. The rabbit model was able to clearly show the 3
      extracted material phases, vascular iodine, oral tungsten, and skeletal calcium.
      Some skeletal calcium was misassigned to the extracted iodine image; however,
      this did not impede the depiction of the vasculature. CONCLUSIONS: The CMEP is a
      straightforward, image-domain approach to extract material signal at dual-energy
      CT. It has particular value for separation of experimental high-Z contrast
      elements from conventional iodine contrast or calcium, even when the exact
      attenuation coefficient profiles of desired contrast materials may be unknown.
      The CMEP is readily implemented in the image-domain within freeware, and can be
      adapted for use with images from multiple vendors.

PMID- 27875340
TI  - Which patients with asymptomatic carotid stenosis benefit from revascularization?
AB  - PURPOSE OF REVIEW: To summarize why there are polarized opinions regarding the
      management of patients with asymptomatic carotid disease and whether it is
      possible to identify patients who might benefit from carotid interventions.
      RECENT FINDINGS: Carotid Revascularization Endarterectomy Versus Stenting Trial
      and Asymptomatic Carotid Trial 1 (ACT-1) recently concluded that outcomes after
      carotid endarterectomy and carotid stenting were not significantly different in
      asymptomatic patients and that procedural risks were below the accepted 3%
      threshold. However, systematic reviews suggest that Carotid Revascularization
      Endarterectomy Versus Stenting Trial/ACT-1 results may not be generalizable into
      routine practice. In parallel, meta-analyses suggest that stroke rates on medical
      therapy may be declining, suggesting that Asymptomatic Carotid Atherosclerosis
      Study/Asymptomatic Carotid Surgery Trial data, which have underpinned every
      practice guideline since 1995, are too historical for use in 2017. A recent
      review has, however, identified a number of clinical/imaging features that may be
      associated with higher rates of stroke on medical therapy. SUMMARY: The majority
      of surgeons/interventionists are unlikely to accept radical changes in practice
      until new randomized trials confirm that the risk of stroke on modern medical
      therapy is significantly lower than that previously accepted. In the interim, it
      would be preferable to target interventions into a smaller cohort who present
      with clinical/imaging features that might render them 'higher risk for stroke' on
      medical therapy.

PMID- 27875341
TI  - Occupational asthma: diagnostic challenges and management dilemmas.
AB  - PURPOSE OF REVIEW: Work-related asthma encompasses both sensitizer-induced and
      irritant-induced occupational asthma as well as work-exacerbated asthma. This
      review summarizes current diagnostic and management strategies for occupational
      asthma. RECENT FINDINGS: Occupational asthma is the most common occupational lung
      disease in the industrialized world. Over 400 agents have been described to cause
      occupational asthma. Specific inhalation challenge is often considered the
      reference method for diagnosis of occupational asthma but specific inhalation
      challenge as well as other diagnostic tests all generate false positive or false
      negative results. Definitive avoidance of the inciting agent is the preferred
      strategy for sensitizer-induced occupational asthma and reduction of exposure is
      the next best step. Immunotherapy is not currently well established and can cause
      systemic reactions. SUMMARY: An accurate diagnosis made in a timely fashion can
      positively impact the health and socioeconomic burden associated with
      occupational asthma. Newer diagnostic tools are promising, but much work needs to
      be done to standardize and validate these testing methods. Primary, secondary,
      and tertiary prevention strategies are crucial for effective management of
      sensitizer-induced occupational asthma.

PMID- 27875342
TI  - The multifaceted roles of inflammasome proteins in cancer.
AB  - PURPOSE OF REVIEW: Inflammasomes are major actors of the innate immune system,
      through their regulation of inflammatory caspases and maturation of IL-1beta and
      IL-18. These multiprotein complexes have been shown to play major roles in
      inflammatory and metabolic diseases and have more recently been implicated in
      tumor development and dissemination. In this review, we address these recent
      findings, focusing particularly on colorectal cancer (CRC) initiation and tumor
      dissemination. RECENT FINDINGS: Based mostly on loss-of-function experiments in
      mouse models, paradoxical results were obtained as both protumoral and
      antitumoral activities were reported. Moreover, several studies report major
      inflammasome-independent functions for some of these innate receptor proteins
      such as absent in melanoma 2, nod-like receptor family pyrin containing 3 (NLRP3)
      or nod-like receptor family CARD containing 4 (NLRC4), functions exerted in
      epithelial cells as well as in immune cells. SUMMARY: The current review
      summarizes recent findings on the implication of inflammasomes and of absent in
      melanoma 2, NLRC4 and NLRP3 inflammasome-independent functions in cancer
      development and dissemination. Although contradictory in certain aspects, these
      studies highlight a lack of understanding of their mechanistic functions and
      regulations in cancer and the need for further investigations.

PMID- 27875343
TI  - More chinks in the armor of cancer: potential for new therapies.

PMID- 27875344
TI  - Patient-centred hand hygiene information in orthopaedics units: an evidence-based
      implementation project.
AB  - AIM: This project aimed to improve patients' knowledge on the importance of hand
      hygiene. It involved providing patients with a patient and family education on
      the importance of hand hygiene using a patient information leaflet that
      introduces the rationale of hand hygiene, possible consequences of poor hand
      hygiene, and the seven steps of hand hygiene. METHODS: This projected used a
      preimplementation and postimplementation audit strategy using the Joanna Briggs
      Institute Practical Application of Clinical Evidence System and Getting Research
      Into Practice programs. The implementation occurred in three phases over a period
      of 6 months from January 2014 to June 2014. The audits took place in two
      orthopaedic wards in a large acute care setting tertiary hospital in Singapore
      and involved a sample size of 54 patients. It involved going through the medical
      records of the cases, assessment of patient knowledge based on the audit
      criteria, and checking if the patients received the patient information leaflet
      on hand hygiene. RESULTS: The postimplementation audit found significant
      improvements in all three audit criteria. The percentage of patients who
      demonstrated knowledge in the importance of hand hygiene saw an improvement of
      48.1%. There was an improvement of 44.5% in nurses' compliance to the
      documentation of patient education being carried out. The percentage of patients
      who received a patient information leaflet on hand hygiene saw an increase of
      36.1%. CONCLUSION: This project demonstrated that a preimplementation and
      postimplementation audit is a viable method to implement change and translate
      evidence into practice. Through this project, patients gained an understanding on
      the importance of hand hygiene and could take better ownership of their well
      being. This may potentially improve hospitalization experience and benefit health
      outcomes. The positive results of this project are contributed by the
      enthusiastic involvement of all the stakeholders, from patients and their
      caregivers to the bedside nurses and nursing leaders. The sustenance will be an
      ongoing challenge to the project.

PMID- 27875345
TI  - Do supraventricular premature beats identify patients at high risk for atrial
      fibrillation?

PMID- 27875346
TI  - Atherosclerosis to predict cardiac events: where and how to look for it.

PMID- 27875347
TI  - Severe low-gradient aortic stenosis, with preserved ventricular function: should
      it be treated?
AB  - Exists a group of patients with small AVA (<0,6 cm/m), and normal LVEF (>=50%)
      who display a low transvalvular flow (LF) [index stroke volume (SVi)<35 ml/m2]
      and/or low transvalvular gradient (LG). This condition is called severe
      paradoxical aortic stenosis (SAO) LFLG. In many studies this condition was
      associated to increased mortality both with medical therapy and with surgical
      intervention. Crucial is define correctly the diagnostical criteria of this
      condition. Indeed there are several specific anatomical and functional
      characteristics useful in differentiating paradoxical severe aortic stenosis from
      the other forms of aortic stenosis. In case of doubt in the diagnostical process,
      the Multidetector Computed Tomography (MDCT) could be useful in quantifying
      calcificazions of the aortic valve. The guidelines European Society of Cardiology
      (ESC) and American College of Cardiology (ACC) recomended aortic valve
      replacement for symptomatic patients with paradoxical LFLG severe aortic
      stenosis, recommending to accurately measure the flow in these patients as to
      differentiate them from those with NFLG and better prognosis.

PMID- 27875348
TI  - Arrhythmias and cardiomyopathy: when arrhythmias come first.

PMID- 27875349
TI  - The revival of old antibiotics for treatment of uncomplicated urinary tract
      infections in the era of antibiotic stewardship.
AB  - PURPOSE OF REVIEW: In the era of increasing antibiotic resistance worldwide, this
      review highlights the advantages of revival of old antibiotics for treatment of
      uncomplicated urinary tract infections (uUTIs). RECENT FINDINGS: Recent studies
      have shown that these four oral old antibiotics, fosfomycin trometamol,
      nitrofurantoin, nitroxoline and pivmecillinam, show no increasing antibiotic
      resistance against uropathogens causing uUTI, are still effective for the
      treatment of uUTI and exhibit only minimal or no collateral damage as compared
      with fluoroquinolones or third-generation cephalosporines. SUMMARY: According to
      the principles of antibiotic stewardship, the prudent use of antibiotics is
      needed. Therefore, recent international and national guidelines already favour
      these old oral antibiotics as first-choice treatment of uUTI. Unfortunately,
      implementation of these guidelines is still suboptimal.

PMID- 27875350
TI  - Pediatric glaucoma: review of recent literature.
AB  - PURPOSE OF REVIEW: The purpose of this review is to update the clinician on the
      recent work in the field of pediatric glaucoma. RECENT FINDINGS: Using the iCare
      tonometer to measure intraocular pressure (IOP) in children is highly successful.
      New data from the Infant Aphakia Treatment Study show that after 5 years of
      follow-up the risk of developing glaucoma is similar between patients that
      receive initial intraocular lens implantation and those who are left aphakic. New
      data show effective lowering of IOP using either approach to trabeculotomy:
      treating the angle partially with trabeculotomes or circumferentially with a
      suture or iTrack microcatheter. Recent data on an updated approach to
      trabeculectomy in children show success in lowering IOP with few complications;
      however, visual outcomes continue to be suboptimal. A separate study shows that
      the addition of tenonectomy may not increase surgical success, but may increase
      survival time and reduce bleb encapsulation. Glaucoma drainage devices in
      general, and the Ahmed implant in particular, continue to be found to be
      moderately successful to control IOP, and are therefore employed, especially
      after initial angle surgery has failed. SUMMARY: Continued work to evaluate the
      techniques used in the clinical and surgical management of pediatric glaucoma
      patients supports that both newer and older approaches remain standard of care.

PMID- 27875351
TI  - Pathogenesis and immunotherapy in cutaneous psoriasis: what can rheumatologists
      learn?
AB  - PURPOSE OF REVIEW: This review presents our current understanding of the
      pathogenesis and treatment of psoriasis with a particular focus on recent areas
      of research and emerging concepts. RECENT FINDINGS: Psoriasis arises in
      genetically predisposed individuals who have an abnormal innate and adaptive
      immune response to environmental factors. Recent studies have identified novel
      genetic, epigenetic and immunological factors that play a role in the disease
      pathogenesis. There is emerging evidence for the role of the skin microbiome in
      psoriasis. Studies have shown reduced diversity and altered composition of the
      skin microbiota in psoriasis. SUMMARY: Recent advances in our understanding of
      the complex immunopathogenesis of psoriasis have led to the identification of
      crucial cytokines and cell signalling pathways that are targeted by a range of
      immunotherapies.

PMID- 27875352
TI  - Does Incorporating Change in APRI or FIB-4 Indices Over Time Improve the Accuracy
      of a Single Index for Identifying Liver Fibrosis in Persons With Chronic
      Hepatitis C Virus Infection?
AB  - BACKGROUND: The aspartate aminotransferase-to-platelet ratio index (APRI) and a
      fibrosis index calculated using platelets (FIB-4) have been proposed as
      noninvasive markers of liver fibrosis. GOALS: To determine APRI/FIB-4 accuracy
      for predicting histologic liver fibrosis and evaluate whether incorporating
      change in index improves test accuracy in hepatitis C virus (HCV)-infected Alaska
      Native persons. STUDY: Using liver histology as the gold standard, we determined
      the test characteristics of APRI to predict Metavir >=F2 fibrosis and FIB-4 to
      predict Metavir >=F3 fibrosis. Index discrimination was measured as the area
      under the receiver operator characteristic curve. We fit a logistic regression
      model to determine whether incorporating change in APRI/FIB-4 over time improved
      index discrimination. RESULTS: Among 283 participants, 46% were female, 48% had a
      body mass index >30, 11% had diabetes mellitus, 8% reported current heavy alcohol
      use. Participants were infected with HCV genotypes 1 (68%), 2 (17%), or 3 (15%).
      On liver histology, 30% of study participants had >=F2 fibrosis and 15% had >=F3
      fibrosis. The positive predictive value of an APRI>1.5/FIB-4>3.25 for identifying
      fibrosis was 77%/78%. The negative predictive value of an APRI<0.5/FIB-4<1.45 was
      91%/87%. The area under the receiver operator characteristic curve of an APRI/FIB
      4 for identifying fibrosis was 0.82/0.84. Incorporating change in APRI/FIB-4 did
      not improve index discrimination. CONCLUSIONS: The accuracy of APRI/FIB-4 for
      identifying liver fibrosis in HCV-infected Alaska Native persons is similar to
      that reported in other populations and could help prioritize patients for
      treatment living in areas without access to liver biopsy. Change in APRI/FIB-4
      was not predictive of degree of fibrosis.

PMID- 27875353
TI  - Cannabinoid Receptor 2 Functional Variant Contributes to the Risk for Pediatric
      Inflammatory Bowel Disease.
AB  - GOALS: We conducted a case-control association analysis to establish the role of
      a common CB2 functional variant, Q63R, in the susceptibility to inflammatory
      bowel disease (IBD). BACKGROUND: Endocannabinoids may limit intestinal
      inflammation through cannabinoid receptor 1 and/or 2 (CB1, CB2). STUDY: We
      genotyped 217 pediatric IBD patients [112 Crohn's disease (CD), 105 ulcerative
      colitis (UC)] and 600 controls for the CB2-Q63R variant by Taqman assay. Data
      were collected from clinical records on age at diagnosis, disease activity,
      duration and location, extraintestinal manifestations, therapy, clinical
      relapses, and need for surgery. RESULTS: We found a significant association of
      the CB2-R63 variant with IBD (allele frequencies, P=0.04; genotype distributions,
      P=0.0006), in particular with CD (allele frequencies, P=0.002; genotype
      distributions, P=0.00005) and with UC only for genotype distributions (P=0.03).
      RR carriers showed an increased risk for developing IBD [odds ratio (OR)=1.82;
      P=0.0002 for IBD; OR=2.02; P=10 for CD; OR=1.63; P=0.02 for UC at 95% confidence
      interval]. Upon genotype-phenotype evaluation, RR patients showed an increased
      frequency of moderate-to-severe disease activity at diagnosis in the case of both
      CD and UC (P=0.01 and P=0.02, respectively) and also an earlier clinical relapse
      in UC (P=0.04). In UC, all the clinical features related to the CB2 risk allele
      were still significantly associated with the variant when analyzed using a
      multivariate logistic regression model (P=0.001). CONCLUSIONS: The CB2-Q63R
      variant contributes to the risk for pediatric IBD, in particular CD. The R63
      variant is associated with a more severe phenotype in both UC and CD. Taken
      together, our data point toward the involvement of the CB2 receptor in the
      pathogenesis and clinical features of pediatric IBD.

PMID- 27875354
TI  - Antiviral Treatment for Colonic Cytomegalovirus Infection in Ulcerative Colitis
      Patients Significantly Improved Their Surgery Free Survival.
AB  - BACKGROUND: The frequency of cytomegalovirus (CMV) colitis in steroid-refractory
      inflammatory bowel disease has been reported to range from 15.8% to 34.0%.
      Infected patients are more likely to become hospitalized, have longer lengths of
      stay, and higher mortality rates. Current data are limited to small scale studies
      and showed conflicting result regarding the role of antiviral therapy. AIMS: (1)
      To investigate the role of antiviral treatment in ulcerative colitis (UC)
      patients with CMV infection. (2) To investigate the role of viremia in the
      outcomes of these patients. MATERIALS AND METHODS: The Cleveland Clinic pathology
      database identified 1478 patients who had colon biopsy and were tested for CMV
      during 1990 to 2013. After inclusion and exclusion, 41 UC patients were selected.
      Among them, 24 (58.5%) received treatment, 17 (41.5%) did not. A total of 14
      demographic data and 4 clinical outcomes (surgery free survival, hospitalization,
      rehospitalization, and mortality) were compared between treated and nontreated
      patients. The same outcomes were also compared in patients who received treatment
      based on their viremia status. RESULTS: All demographic variables are similar
      between those treated and nontreated groups. Antiviral therapy significantly
      improved the surgery free survival within 30 days, and lasted 70 months (P<0.01).
      In contrast, hospitalization, rehospitalization, and mortality were comparable
      (P>0.05). No significant difference was observed in any of the clinical outcomes
      based on viremia status. CONCLUSIONS: Our small scale study demonstrates that
      antiviral treatment for colonic CMV infection significantly improves the surgery
      free survival short-term and long-term in patients with UC.

PMID- 27875355
TI  - Novel Mutations in EPCAM Cause Congenital Tufting Enteropathy.
AB  - BACKGROUND AND AIMS: Congenital tufting enteropathy (CTE) is a rare autosomal
      recessive form of intractable diarrhea of infancy. Patients develop chronic
      diarrhea within days after birth, leading to severe malabsorption and significant
      mortality. CTE is characterized by subtotal villous atrophy with crypt
      hyperplasia. Typical features include abnormal villi in the intestinal epithelium
      and disorganization of surface enterocytes with focal crowding, resembling tufts.
      The pathogenesis of CTE remains poorly understood. CTE has been reported in
      Western populations, but until now had not been reported in China. The objective
      of this study was to identify the gene responsible for CTE in a Chinese
      individual. METHODS: A 13-year-old girl with suspected CTE, whose parents were
      both healthy, was evaluated in our clinic. Tissues were obtained by endoscopy and
      examined by electron microscopy. Genomic DNA, extracted from the peripheral blood
      of the child and parents, was subjected to whole-exome sequencing. After
      mutations in the gene encoding epithelial cell adhesion molecule (EPCAM) were
      identified, expression of EPCAM was examined by immunohistochemistry staining.
      RESULTS: Whole-exome sequencing revealed compound heterozygous mutations in EPCAM
      in the patient, with immunohistochemical analysis showing complete loss of EPCAM
      expression in the intestinal villi and crypts. CONCLUSIONS: We identified
      compound heterozygous mutations in EPCAM, with loss of EPCAM expression in
      duodenal enterocytes, in a patient with intractable diarrhea since infancy who
      was subsequently diagnosed with CTE. This is the first case of CTE to be reported
      in a Chinese patient.

PMID- 27875356
TI  - Corticosteroids and Thiopurines, But Not Tumor Necrosis Factor Antagonists, are
      Associated With Cytomegalovirus Reactivation in Inflammatory Bowel Disease: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: The association between cytomegalovirus (CMV) reactivation and
      individual immunosuppressive agents in inflammatory bowel disease (IBD) has not
      been clearly defined. Therefore, we performed a systematic review and meta
      analysis to assess this association. METHODS: Multiple electronic databases were
      searched systematically through July 2015 for observational studies reporting CMV
      reactivation (based on serum-based or tissue-based tests) in IBD patients
      stratified by medication exposure. We estimated summary odds ratios (ORs) and 95%
      confidence intervals (CI) using random-effects model. Study quality was assessed
      using the Newcastle-Ottawa scale. RESULTS: Sixteen observational studies were
      identified. As compared with nonexposed patients, exposure to corticosteroids
      (CS) (12 studies, 1180 patients, 52.3% exposed; OR, 2.05; 95% CI, 1.40-2.99) and
      thiopurines (14 studies, 1273 patients, 24.1% exposed; OR, 1.56; 95% CI, 1.01
      2.39) was associated with increased risk of CMV reactivation. In contrast, as
      compared with patients not exposed to tumor necrosis factor (TNF) antagonists,
      exposure to TNF antagonists was not associated with an increased risk of CMV
      reactivation (7 studies, 818 patients, 18.5% exposed; OR, 1.44; 95% CI, 0.93
      2.24). The results remained stable for CS and thiopurines when the analysis was
      limited to hospitalized patients, and by a tissue-based diagnosis. Studies were
      limited in the ability to assess the impact of concomitant immunosuppressive
      therapy, duration of medication exposure, and disease severity. CONCLUSIONS: On
      the basis of 16 observational studies, exposure to CS or thiopurines, but not TNF
      antagonists, was associated with an increased risk of CMV reactivation in IBD
      patients.

PMID- 27875357
TI  - Optimal Timing of Endoscopic Retrograde Cholangiopancreatography in Acute
      Cholangitis.
AB  - OBJECTIVES: Acute cholangitis mandates resuscitation, antibiotic therapy, and
      biliary decompression. Our aim was to define the optimal timing of endoscopic
      retrograde cholangiopancreatography (ERCP) for patients with acute cholangitis.
      METHODS: Clinical data on all cases of cholangitis managed by ERCP were
      prospectively collected from September 2010 to July 2013. The clinical impact of
      the time to ERCP, defined as the time from presentation in the emergency
      department to the commencement of the ERCP, was determined. The primary outcome
      was length of hospitalization. Secondary outcomes included vasopressor use,
      endotracheal intubation, intensive care unit admission, and death. RESULTS: ERCP
      was successful in 182 (92%) of 199 patients with cholangitis. Length of
      hospitalization was significantly longer for patients undergoing ERCP at >=48
      versus <48 hours (median 9.1 vs. 6.5 d, P=0.004) even though patients having ERCP
      at >=48 hours were less sick as indicated by less frequent intensive care unit
      admission [odds ratio,0.3; 95% confidence interval (CI), 0.2-0.6]. Multivariate
      analysis revealed that hospitalization increased by 1.44 days for every day ERCP
      was delayed (P<0.001). Comparison of ERCP>=72 versus <72 hours revealed odds
      ratios of 2.6 (95% CI, 1.0-7.0) for vasopressor requirement and 3.6 (95% CI, 0.8
      15.9) for mortality. Time to ERCP did not impact technical success or procedural
      adverse events. CONCLUSIONS: ERCP should be performed within 2 days of
      presentation as a delay of 48 or more hours is associated with disproportionate
      increase in hospital stay. Delay>72 hours is associated with additional adverse
      outcomes including hypotension requiring vasopressor support.

PMID- 27875358
TI  - "Mesalazine in the Treatment of Symptomatic Uncomplicated Diverticular Disease:
      Reply".

PMID- 27875359
TI  - Symptom Index or Symptom Association Probability?: A Closer Look at Symptom
      Association in Suspected GERD Patients.
AB  - BACKGROUND: Symptom index (SI) and symptom association probability (SAP) are
      popular methods used to measure symptom association in patients with
      gastroesophageal reflux disease (GERD). AIM: To investigate whether these 2
      methods yield similar results in analysis of both typical and atypical GERD
      symptoms. MATERIALS AND METHODS: Combined impedance-pH reflux studies of 1471
      patients tested for possible GERD symptoms from January 2010 to May 2015 were
      reviewed. SI and SAP were analyzed for typical and atypical GERD symptoms
      including heartburn, regurgitation, indigestion, chest pain, cough, and throat
      clearing (TC). Patients who reported <3 symptom events during the 24-hour
      monitoring period were excluded. ON and OFF proton pump inhibitor (PPI) groups
      were reviewed. Kappa coefficient (kappa) rather than simple percentage was used
      to measure the agreement rate. Simple percentage agreement is a less reliable
      method compared with kappa. RESULTS: On PPI therapy, there was a good kappa
      between SI and SAP for regurgitation (0.68) and indigestion (0.64), moderate for
      heartburn (0.48) and chest pain (0.51), and poor for cough (0.33) and TC (0.29).
      There was a lower kappa OFF PPI therapy for heartburn (0.36), regurgitation
      (0.44), and indigestion (0.50). But there was no difference in kappa for chest
      pain (0.61), cough (0.29), and TC (0.33). CONCLUSIONS: SI and SAP showed better
      agreement for patients with typical GERD symptoms and even better when tested ON
      PPI. A better symptom association method is needed for patients with atypical
      GERD symptoms.

PMID- 27875360
TI  - Outcomes After Conservative, Endoscopic, and Surgical Treatment of Groove
      Pancreatitis: A Systematic Review.
AB  - BACKGROUND: Groove pancreatitis (GP) is a focal form of chronic pancreatitis
      affecting the paraduodenal groove area, for which consensus on diagnosis and
      management is lacking. GOALS: We performed a systematic review of the literature
      to determine patient characteristics and imaging features of GP and to evaluate
      clinical outcomes after treatment. RESULTS: Eight studies were included reporting
      on 335 GP patients with a median age of 47 years (range, 34 to 64 y), with 90%
      male, 87% smokers, and 87% alcohol consumption, and 47 months (range, 15 to 122
      mo) of follow-up. Most patients presented with abdominal pain (91%) and/or weight
      loss (78%). Imaging frequently showed cystic lesions (91%) and duodenal stenosis
      (60%).Final treatment was conservative (eg, pain medication) in 29% of patients.
      Endoscopic treatment (eg, pseudocyst drainage) was applied in 19% of patients-34%
      of these patients were subsequently referred for surgery. Overall, 59% of
      patients were treated surgically (eg, pancreatoduodenectomy). Complete symptom
      relief was observed in 50% of patients who were treated conservatively, 57% who
      underwent endoscopic treatment, and 79% who underwent surgery. CONCLUSIONS: GP is
      associated with male gender, smoking, and alcohol consumption. The vast majority
      of patients presents with abdominal pain and with cystic lesions on imaging.
      Although surgical treatment seems to be the most effective, both conservative and
      endoscopic treatment are successful in about half of patients. A stepwise
      treatment algorithm starting with the least invasive treatment options seems
      advisable.

PMID- 27875361
TI  - High Mobility and HIV Prevalence Among Female Market Traders in East Africa in
      2014.
AB  - BACKGROUND: The contribution of women's mobility to the HIV/AIDS epidemic in
      Africa is poorly understood, despite women's high mobility and evidence that it
      is associated with higher-risk sexual behavior. We sought to measure levels of
      mobility, HIV prevalence, and related risk behaviors among female traders in
      Kisumu, Kenya. METHODS: We used global positioning system mapping to develop a
      probability-based sample and recruited 305 female market traders for
      participation in a survey and voluntary HIV counseling and testing in 2014. We
      estimated HIV prevalence and fitted logistic regression models to measure
      associations between mobility, risk behaviors, and HIV infection. RESULTS: HIV
      prevalence was 25.6% (95% confidence interval: 21.0 to 30.8); 11.5% had migrated
      (changed residence, over county, or national boundary) in the past year and 39.3%
      in the past 5 years. More than one-third (38.3%) spent nights away from main
      residence in the past month, with 11.4% spending more than a week away. Multiple
      partners were reported by 13.1% of women in the last year; 16% of married women
      reported a concurrent partnership. Mobility was not significantly associated with
      HIV prevalence, although recent short-term mobility was significantly correlated
      with higher numbers of sexual partners in the past year. CONCLUSIONS: Female
      market traders were highly mobile, and HIV prevalence among traders was higher
      than in the general population of women of reproductive age in Kisumu (15.3% in
      2013), and Nyanza Province, Kenya (16.1% in 2012). High HIV prevalence and risk
      behavior among women in this study warrant accelerated attention to HIV
      prevention and care needs of mobile women, including market traders.

PMID- 27875362
TI  - Relationship Between HIV Infection, Antiretroviral Therapy, Inflammatory Markers,
      and Cerebrovascular Endothelial Function Among Adults in Urban China.
AB  - BACKGROUND: Cerebrovascular risk is increased in people living with HIV infection
      compared with age-matched uninfected individuals. Cerebrovascular endothelial
      dysfunction related to antiretroviral therapy (ART) and inflammation may
      contribute to higher stroke risk in HIV infection. METHODS: We compared cerebral
      vasoreactivity-a measure of cerebrovascular endothelial function assessed by the
      breath-holding index (BHI) using transcranial Doppler ultrasound-between
      virologically suppressed Chinese HIV-infected individuals followed in an HIV
      clinic in Beijing, China, and uninfected controls. We constructed mixed-effects
      models to evaluate the association of HIV, ART, and inflammatory markers with
      cerebral vasoreactivity. RESULTS: In an unadjusted model, HIV infection was
      associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus
      1.26, P = 0.079). In multivariable analyses, cholesterol modified the association
      between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At
      a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral
      vasoreactivity (BHI -0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L,
      the reduction in cerebral vasoreactivity associated with HIV was no longer
      statistically significant (BHI -0.05, P = 0.64). Among HIV-infected individuals,
      use of lopinavir/ritonavir compared with efavirenz was associated with lower
      cerebral vasoreactivity (BHI -0.24, P = 0.040). We did not find a significant
      association between inflammatory markers and cerebral vasoreactivity.
      CONCLUSIONS: Cerebrovascular endothelial dysfunction associated with HIV
      infection may be most relevant for individuals with less traditional vascular
      risk, such as those with lower cholesterol. Further study of the impact of ART on
      cerebrovascular endothelial function is warranted to aid with ART selection in
      individuals at high cerebrovascular risk.

PMID- 27875364
TI  - Attenuation of Choroidal Thickness in Patients With Alzheimer Disease: Evidence
      From an Italian Prospective Study.
AB  - INTRODUCTION: To compare the 12-month choroidal thickness (CT) change between
      Alzheimer disease (AD) patients and normal subjects. METHODS: In this
      prospective, observational study, 39 patients with a diagnosis of mild to
      moderate AD and 39 age-matched control subjects were included. All the subjects
      underwent neuropsychological (Mini Mental State Examination, Alzheimer disease
      Assessment Scale-Cognitive Subscale, and the Clinical Dementia Rating Scale) and
      ophthalmological evaluation, including spectral domain optical coherence
      tomography, at baseline and after 12 months. CT was measured manually using the
      caliper tool of the optical coherence tomography device. RESULTS: After 12
      months, AD patients had a greater reduction of CT than controls (P<=0.05,
      adjusted for baseline CT, age, sex, axial length, and smoking). DISCUSSION: CT in
      patients with AD showed a rate of thinning greater than what could be expected
      during the natural course of aging.

PMID- 27875366
TI  - Resolve to make healthy living a habit.

PMID- 27875363
TI  - PMTCT Option B+ Does Not Increase Preterm Birth Risk and May Prevent Extreme
      Prematurity: A Retrospective Cohort Study in Malawi.
AB  - OBJECTIVE: To estimate preterm birth risk among infants of HIV-infected women in
      Lilongwe, Malawi, according to maternal antiretroviral therapy (ART) status and
      initiation time under Option B+. DESIGN: A retrospective cohort study of HIV
      infected women delivering at >=27 weeks of gestation, April 2012 to November
      2015. Among women on ART at delivery, we restricted our analysis to those who
      initiated ART before 27 weeks of gestation. METHODS: We defined preterm birth as
      a singleton live birth at >=27 and <37 weeks of gestation, with births at <32
      weeks classified as extremely to very preterm. We used log-binomial models to
      estimate risk ratios and 95% confidence intervals for the association between ART
      and preterm birth. RESULTS: Among 3074 women included in our analyses, 731
      preterm deliveries were observed (24%). Overall preterm birth risk was similar in
      women who had initiated ART at any point before 27 weeks and those who never
      initiated ART (risk ratio = 1.14; 95% confidence interval: 0.84 to 1.55), but
      risk of extremely to very preterm birth was 2.33 (1.39 to 3.92) times as great in
      those who never initiated ART compared with those who did at any point before 27
      weeks. Among women on ART before delivery, ART initiation before conception was
      associated with the lowest preterm birth risk. CONCLUSIONS: ART during pregnancy
      was not associated with preterm birth, and it may in fact be protective against
      severe adverse outcomes accompanying extremely to very preterm birth. As
      preconception ART initiation appears especially protective, long-term retention
      on ART should be a priority to minimize preterm birth in subsequent pregnancies.

PMID- 27875365
TI  - Clear Cell Papulosis: Report of a Case With Unique Clinical and Histologic
      Findings.
AB  - Clear cell papulosis is a rare, self-limited, benign disease of early childhood,
      characterized by white macules and flat papules over the milk line.
      Histopathologically, it is characterized by scattered clear cells throughout the
      basal and/or suprabasal epidermal layers, which-as clear cells of Toker of the
      nipple do-typically express cytokeratin 7. They also exhibit other markers
      expected for adenoid differentiation, such as low-molecular weight cytokeratins,
      carcinoembryonic antigen, epithelial membrane antigen, and mucin. The age of
      onset, distribution of lesions, histopathology, and its benign behavior nature
      help to exclude clinically similar conditions, either benign or malignant. The
      authors report a case of clear cell papulosis in a 7-year-old Brazilian girl in
      whom lesions were observed on the legs and histologically formed by solid and
      adenoid aggregates of clear cells, in a similar fashion than clear fetal cells of
      Toker.

PMID- 27875367
TI  - Cardiac surgery-associated acute kidney injury: much improved, but still long
      ways to go.

PMID- 27875369
TI  - Echocardiography for Less-Invasive Implantation of Left Ventricular Assist
      Devices.
AB  - New surgical techniques aim for less-invasive implantation of left ventricular
      assist devices (LVADs) via small surgical incision sites. Echocardiography plays
      an important role during patient selection and guidance of the procedure. The
      surgical incision site can be identified preoperatively by transthoracic
      echocardiography. Intraoperative identification of left ventricular apex, de
      airing, and monitoring heart function is performed by transesophageal
      echocardiography. This article highlights special echocardiographic
      considerations during less-invasive LVAD implantation surgeries.

PMID- 27875370
TI  - Myocardial Infarction After Accidental Minoxidil Poisoning.

PMID- 27875368
TI  - Analgesic Effect and Functional Improvement Caused by Radiofrequency Treatment of
      Genicular Nerves in Patients With Advanced Osteoarthritis of the Knee Until 1
      Year Following Treatment.
AB  - BACKGROUND AND OBJECTIVES: Radiofrequency ablation of genicular nerves has proved
      to be successful in relieving pain and incapacity caused by osteoarthritis of the
      knee. However, long-term efficacy of such a treatment remains to be assessed. The
      current study aimed to reproduce radiofrequency neurotomy of genicular nerves to
      manage gonarthrosis pain and disability and establish therapeutic response until
      1 year after intervention. METHODS: This single-center, prospective,
      observational, noncontrolled, longitudinal study included patients with grade 3
      to 4 gonarthrosis suffering from intractable knee pain, scoring 5 or more on the
      visual analog scale (VAS) during >6 months. Therapy was based on ultrasound
      guided radiofrequency neurotomy of the superior medial, superior lateral and
      inferior medial genicular nerves. Visual analog scale and Western Ontario and
      McMaster Universities Osteoarthritis scores were assessed before therapy and at
      1, 6, and 12 months following treatment. RESULTS: Radiofrequency neurotomy of
      genicular nerves significantly reduced perceived pain (VAS) and disability
      (Western Ontario and McMaster Universities Osteoarthritis) in the majority of
      participants, without untoward events. The proportion of participants with
      improvement of 50% or greater in pretreatment VAS scores at 1, 6, and 12 months
      following intervention were 22/25 (88%), 16/25 (64%) and 8/25 (32%),
      respectively. CONCLUSIONS: Ultrasound-guided radiofrequency neurotomy of
      genicular nerves alleviates intractable pain and disability in the majority of
      patients with advanced osteoarthritis of the knee. Such a treatment is safe and
      minimally invasive and can be performed in an outpatient setting. The beneficial
      effect of treatment started to decline after 6 months, but even 1 year after the
      intervention, 32% of patients reported 50% improvement or greater in pretreatment
      VAS scores.

PMID- 27875371
TI  - Topiramate Blood Levels During Polytherapy for Epilepsy in Children.
AB  - BACKGROUND: The therapeutic range of topiramate (TPM) blood level is not set
      because the efficacy and safety are not considered to be related to the level.
      However, the therapeutic target without side effects is necessary, so the optimal
      range of TPM blood level was analyzed in this study. STUDY QUESTION: This study
      was conducted to evaluate the efficacy of TPM over 2 years and the utility of
      measuring blood levels of TPM during the follow-up of epileptic patients. STUDY
      DESIGN: Thirty patients (18 males, 12 females; age range, 6 months-15 years) were
      treated with TPM for epilepsy. The initial dosage of TPM was 1-3 mg.kg.d. If the
      effect proved insufficient after 2 weeks, the dosage was increased to 4-9
      mg.kg.d. MEASURES AND OUTCOMES: Blood levels of TPM were measured by liquid
      chromatography-tandem mass spectrometry at 1, 6, 12, and 24 months after levels
      reached steady state. The efficacy of TPM was evaluated by the reduction in
      epileptic seizure rate (RR) at the time of blood sampling. Statistical analysis
      was performed using the Mann-Whitney U test. RESULTS: A positive correlation was
      seen between blood levels and maintenance dosages, but no correlation was
      observed between blood levels and RR. Any significant difference was not
      identified in TPM levels between the effective group (RR >=50%) and the
      ineffective group (RR <50%; P = 0.159). In the subgroup of patients who did not
      use valproic acid, a significant difference in TPM levels was apparent between
      the effective and ineffective groups (P = 0.029). The optimal range of TPM was
      advocated 3.5-5.0 MUg/mL. The optimal range was set, so that ranges did not
      overlap between the effective and ineffective groups. No patients experienced any
      side effects. CONCLUSIONS: Measuring blood levels of TPM based on the
      classification of concomitant drugs and adjusting the dosage to reach the optimal
      range were recommended.

PMID- 27875372
TI  - Cutaneous malignancies in HIV.
AB  - PURPOSE OF REVIEW: As patients with HIV infection are living longer with their
      disease, we have seen the evolution of skin cancer in this population. Cancer
      registries have not documented the incidence and prevalence of these cancers but
      we do have relevant data from cohorts. This article attempts to bring to light
      the extent to which skin cancer is an issue in HIV disease both domestically and
      internationally. RECENT FINDINGS: Squamous cell cancer is increasing in incidence
      in the United States and elsewhere. The anatomic locations of skin cancer vary
      according to demographics, host factors, and environment. In this review,
      squamous cell cancer will be contrasted to the other skin cancers namely,
      melanoma, and basal cell cancers. SUMMARY: As our HIV population ages, clinicians
      should be informed as to the relevant risk factors for development of skin
      cancer. With the increasing incidence of these cancers in the modern era of HIV,
      clinicians and researchers will be informed with regard to prevention and
      treatment strategies.

PMID- 27875373
TI  - Revisiting erythroleukemia.
AB  - PURPOSE OF REVIEW: The 2016 WHO classification of hematopoietic and lymphoid
      neoplasms alters the diagnostic criteria for erythroleukemia, including
      eliminating the erythroid/myeloid type of acute erythroleukemia, which was a
      prior subcategory of acute myeloid leukemia, not otherwise specified. Only pure
      erythroid leukemia remains in the WHO classification. This review will summarize
      the literature that contributed to that classification change as well as recent
      literature on the significance of the change. RECENT FINDINGS: There is now a
      large body of literature on the negative prognostic impact of erythroid
      predominance, defined as 50% or more bone marrow erythroid cells, in
      myelodysplastic syndromes (MDSs). Recent studies have found similarities between
      erythroleukemia, especially the erythroid/myeloid type, and the erythroid-rich
      MDS cases. On the basis of these data, the WHO now reclassifies cases of the
      prior erythroid/myeloid acute erythroleukemia group based on the total blast cell
      count. This change moves such cases into an MDS category, usually MDS with excess
      blasts. This approach, however, may cloud the significance of erythroid
      predominance in this group of patients. SUMMARY: The report clarifies the current
      criteria for a diagnosis of erythroleukemia as well as the ongoing challenges in
      classifying this group of erythroid rich bone marrow disorders.

PMID- 27875374
TI  - Implications of molecular genetic diversity in myelodysplastic syndromes.
AB  - PURPOSE OF REVIEW: Myelodysplastic syndromes (MDS) have remarkably diverse
      somatic mutation patterns that can be challenging to interpret clinically. Yet,
      genetic information is increasingly available to physicians. This review will
      examine several implications of genetic diversity in MDS. RECENT FINDINGS:
      Somatic mutations can serve as clinically relevant biomarkers in MDS. Molecular
      subtypes may exist that share clinical features including risk of progression to
      acute myeloid leukemia, response to treatment, and overall survival. Several
      mutated genes are known to have prognostic value that is independent of common
      risk stratification tools. Mutations of several genes identify low-blast
      percentage patients with greater than predicted disease risk while only SF3B1
      mutations predict lower disease risk than expected. Mutations of TP53 are
      associated with adverse features, yet demonstrate inferior outcomes than
      predicted by these risk factors. SF3B1 and TP53 mutations may identify clinically
      relevant subtypes of MDS and allow for better refinement of risk within these
      groups. Using somatic mutations to diagnose MDS is more challenging because they
      can occur in healthy individuals. Yet, patients with unexplained cytopenias have
      a high rate of clonal hematopoiesis that may be an important risk factor to
      identify clinically. SUMMARY: Patterns of somatic mutations are diverse in MDS,
      but can inform the prediction of prognosis and aid in its diagnosis.

PMID- 27875375
TI  - Management of venous thromboembolism in myeloproliferative neoplasms.
AB  - PURPOSE OF REVIEW: Venous thromboembolism is frequent in chronic
      myeloproliferative neoplasms (MPN). The current strategy for its management
      includes cytoreductive therapy and antithrombotic prophylaxis, but many issues
      remain uncertain. In this review, the risk factors and prevention of recurrences
      will be discussed. RECENT FINDINGS: Around one-third of patients with
      polycythemia vera and essential thrombocythemia experience a major thrombosis at
      diagnosis or during follow-up. According to the European Leukemia Net guidelines,
      these patients must be included in the high-risk group for thrombotic recurrence
      and should be treated with cytoreduction and antiplatelet or anticoagulant drugs
      in the presence of arterial or venous thrombosis, respectively. Despite this
      treatment, the annual incidence of recurrence after the first venous thrombosis
      varies from 4.2 to 6.5% on vitamin K-antagonists and is doubled after
      discontinuation. The highest incidence of recurrence occurs after cerebral and
      hepatic vein thrombosis (8.8 and 8 per 100 pt-years, respectively). The
      occurrence of major bleeding on vitamin K-antagonists is similar to a non-MPN
      population and accounts for a rate of 1.8-2.4 per 100 pt-years. SUMMARY: After
      venous thrombosis, the incidence of recurrence in MPN remains elevated, which
      suggested there was a need to review the current recommendations of primary and
      secondary prophylaxis.

PMID- 27875376
TI  - Rhinitis: adherence to treatment and new technologies.
AB  - PURPOSE OF REVIEW: Nonadherence to treatment is a major issue in approximately
      50% of patients suffering from chronic diseases. The availability of new
      technologies could represent a possible way to improve patients' engagement and
      adherence in a real-life setting. Research and technology tools made available or
      in process of being made available to patients with allergic diseases and their
      physicians could potentially improve the management of these disease in daily
      life by improving adherence. In this review, we sought to outline many of the
      recent advances in these technological approaches. RECENT FINDINGS: Short Message
      Service (SMS) reminder, social networks, wearable devices, mobile applications
      (Apps), monitoring systems of inhaled device use, often presented as 'serious
      game' are changing the way of approaching to chronic disease, such as rhinitis,
      management. SUMMARY: Studies of the role played by various technologies in
      improving adherence to treatment in rhinitis are still limited as compared with
      other diseases such as asthma, but the results are encouraging. Further studies
      in this area may lead to the discovery of novel management approaches that is
      easy to be integrated in patients' daily life.

PMID- 27875377
TI  - Spinal Cord Stimulation for Refractory Angina Pectoris: A Systematic Review and
      Meta-analysis.
AB  - OBJECTIVES: Paresthesia-free stimulation such as high frequency and burst have
      been demonstrated as effective therapies for neuropathic pain. The aim of this
      meta-analysis was to evaluate the efficacy and safety of conventional spinal cord
      stimulation (SCS) in the treatment of refractory angina pectoris (RAP). MATERIALS
      AND METHODS: Relevant randomized controlled trials that investigated SCS for
      patients with RAP were comprehensively searched in Medline, Pubmed, Embase, and
      Cochrane Library. Five meta-analyses were performed examining the changes in
      Canadian Cardiovascular Society classes, exercise time, Visual Analog Scale (VAS)
      scores of pain, Seattle Angina Questionnaire, and nitroglycerin use in RAP
      patients after SCS therapy. We analyzed standardized mean differences (MD) and
      95% confidence intervals (CIs) for each outcome by Review Manager 5.0 and STATA
      12.0. RESULTS: A total of 12 randomized controlled trials involving 476 RAP
      patients were identified. A trend of reduction in the angina frequency (MD=-9.03,
      95% CI, -15.70 to -2.36) and nitroglycerin consumption (MD=-0.64, 95% CI, -0.84
      to -0.45) could be observed in the SCS group. Compared with the control group,
      SCS showed benefit on increasing exercise time (MD=0.49, 95% CI, 0.13-0.85) and
      treatment satisfaction (MD=6.87, 95% CI, 2.07-11.66) with decreased VAS scores of
      pain (MD=-0.50, 95% CI, -0.81 to -0.20) and disease perception (MD=-8.34, 95% CI,
      -14.45 to -2.23). However, the result did not reach the significance level in
      terms of physical limitation (95% CI, -8.75 to 3.38; P=0.39) or angina stability
      (95% CI, -7.55 to 3.67; P=0.50). DISCUSSION: The current meta-analysis suggested
      that SCS was a potential alternative in the treatment of PAP patients. Further
      investigation for finding the appropriate intensity of stimulation is required
      before this treatment should be widely recommended and applied.

PMID- 27875378
TI  - Cushing Syndrome in Carney Complex: Clinical, Pathologic, and Molecular Genetic
      Findings in the 17 Affected Mayo Clinic Patients.
AB  - Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder
      that includes Cushing syndrome (CS). To establish the Mayo Clinic experience with
      the CS component, including its clinical, laboratory, and pathologic findings, we
      performed a retrospective search of the patient and pathologic databases of Mayo
      Clinic in Rochester, MN, for patients with CNC and clinical or laboratory
      findings of CS. Thirty-seven patients with CNC were identified. Twenty-nine had
      clinical, pathologic, or laboratory evidence of an adrenocortical disorder.
      Seventeen had classic CS; 15 underwent bilateral, subtotal, or partial unilateral
      adrenalectomy, and 2 had no treatment. Pathologically, the glands were normal
      sized or slightly enlarged with multiple small (1 to 4 mm), brown, black, and
      yellow micronodules (primary pigmented nodular adrenocortical disease; PPNAD).
      Three glands each had a mass: a 2 cm adenoma, a 1.5 cm macronodule, and an
      unencapsulated 1.8 cm myelolipoma. Fourteen of the patients were alive at follow
      up, and 3 were deceased; 2 of the latter had PPNAD at autopsy, and the third had
      PPNAD at surgery. Twelve patients without clinical features of classic CS had
      abnormal adrenocortical testing results; none developed classic CS during follow
      up (mean, 10 y). Autopsy findings in 1 showed bilateral vacuolated cell cortical
      hyperplasia.

PMID- 27875379
TI  - The decision neuroscience perspective on suicidal behavior: evidence and
      hypotheses.
AB  - PURPOSE OF REVIEW: Suicide attempts are usually regretted by people who survive
      them. Furthermore, addiction and gambling are over-represented among people who
      attempt or die by suicide, raising the question whether their decision-making is
      impaired. Advances in decision neuroscience have enabled us to investigate
      decision processes in suicidal people and to elucidate putative neural substrates
      of disadvantageous decision-making. RECENT FINDINGS: Early studies have linked
      attempted suicide to poor performance on gambling tasks. More recently,
      functional MRI augmented with a reinforcement learning computational model
      revealed that impaired decision-making in suicide attempters is paralleled by
      disrupted expected value (expected reward) signals in the ventromedial prefrontal
      cortex. Behavioral studies have linked increased delay discounting to low
      lethality/poorly planned attempts, multiple attempts, and the co-occurrence of
      attempted suicide and addiction. This behavioral tendency may be related to
      altered integrity of the basal ganglia. By contrast, well-planned, serious
      suicide attempts were associated with intact/diminished delay discounting. One
      study has linked high-lethality suicide attempts and impaired social decision
      making. SUMMARY: This emerging literature supports the notion that various
      impairments in decision-making - often broadly related to impulsivity - may mark
      different pathways to suicide. We propose that aggressive and self-destructive
      responses to social stressors in people prone to suicide result from a
      predominance of automatic, Pavlovian processes over goal-directed computations.

PMID- 27875381
TI  - Diabetes Self-management Quality Improvement Initiative for Medically Underserved
      Patients.
AB  - The burden of diabetes is greater for minorities and medically underserved
      populations in the United States. An evidence-based provider-delivered diabetes
      self-management education intervention was implemented in a federally qualified
      health center for medically underserved adult patients with type 2 diabetes. The
      findings provide support for the efficacy of the intervention on improvement in
      self-management behaviors and glycemic control among underserved patients with
      diabetes, while not substantially changing provider visit time or workload.

PMID- 27875382
TI  - Incorporation of Leadership Rounds in CAUTI Prevention Efforts.
AB  - Leadership engagement is an important aspect of integrating best practices at the
      bedside. The catheter-associated urinary tract infection (CAUTI) prevention
      workgroup at our academic medical center implemented leadership rounding in
      partnership with clinical staff to increase participation in CAUTI prevention
      initiatives on inpatient units. There was an associated decrease in urinary
      catheter utilization and CAUTI rates. Implementation of leadership rounds should
      be considered as a part of comprehensive CAUTI prevention efforts in health care
      settings.

PMID- 27875383
TI  - Predictors of Hospital Nurses' Safety Practices: Work Environment, Workload, Job
      Satisfaction, and Error Reporting.
AB  - Nurses' safety practices of medication administration, prevention of falls and
      unplanned extubations, and handover are essentials to patient safety. This study
      explored the prediction between such safety practices and work environment
      factors, workload, job satisfaction, and error-reporting culture of 1429
      Taiwanese nurses. Nurses' job satisfaction, error-reporting culture, and one
      environmental factor of nursing quality were found to be major predictors of
      safety practices. The other environment factors related to professional
      development and participation in hospital affairs and nurses' workload had
      limited predictive effects on the safety practices. Increasing nurses' attention
      to patient safety by improving these predictors is recommended.

PMID- 27875384
TI  - Improving Nursing Communication Skills in an Intensive Care Unit Using Simulation
      and Nursing Crew Resource Management Strategies: An Implementation Project.
AB  - Effective interprofessional communication is critical to patient safety. This pre
      /postimplementation project used a multifaceted educational strategy with high
      fidelity simulation to introduce evidence-based communication tools, adapted from
      Nursing Crew Resource Management, to intensive care unit nurses. Results
      indicated that participants were satisfied with the education, and their
      perceptions of interprofessional communication and knowledge improved. Teams (n =
      16) that used the communication tools during simulation were more likely to
      identify the problem, initiate key interventions, and have positive outcomes.

PMID- 27875386
TI  - Correlation Between Posttraumatic Growth and Posttraumatic Stress Disorder
      Symptoms Based on Pearson Correlation Coefficient: A Meta-Analysis.
AB  - The literature on posttraumatic growth (PTG) is burgeoning, with the
      inconsistencies in the literature of the relationship between PTG and
      posttraumatic stress disorder (PTSD) symptoms becoming a focal point of
      attention. Thus, this meta-analysis aims to explore the relationship between PTG
      and PTSD symptoms through the Pearson correlation coefficient. A systematic
      search of the literature from January 1996 to November 2015 was completed. We
      retrieved reports on 63 studies that involved 26,951 patients. The weighted
      correlation coefficient revealed an effect size of 0.22 with a 95% confidence
      interval of 0.18 to 0.25. Meta-analysis provides evidence that PTG may be
      positively correlated with PTSD symptoms and that this correlation may be
      modified by age, trauma type, and time since trauma. Accordingly, people with
      high levels of PTG should not be ignored, but rather, they should continue to
      receive help to alleviate their PTSD symptoms.

PMID- 27875385
TI  - Effects of Linagliptin on Vessel Wall Healing in the Rat Model of Arterial Injury
      Under Normal and Diabetic Conditions.
AB  - Diabetic patients suffer an increased risk of restenosis and late stent
      thrombosis after angioplasty, complications which are related to a defective
      reendothelialization. Dipeptidyl peptidase-4 inhibitors have been suggested to
      exert a direct effect on endothelial and smooth muscle cells (SMCs). Therefore,
      the objective was to study if the dipeptidyl peptidase-4 inhibitor linagliptin
      could influence vascular repair and accelerate reendothelialization after
      arterial injury in healthy and diabetic animals. Diabetic Goto-Kakizaki and
      healthy Wistar rats were subjected to arterial injury and treated with
      linagliptin or vehicle. Vessel wall healing was monitored noninvasively using
      ultrasound, and on sacrifice, with Evans blue staining and immunohistochemistry.
      The effect of linagliptin on SMCs was also studied in vitro. We found that
      linagliptin reduced the proliferation and dedifferentiation of SMCs in vitro, and
      modulated the inflammatory response in the SMCs after arterial injury in vivo.
      However, these effects of linagliptin did not affect the neointima formation or
      the reendothelialization under normal and diabetic conditions. Although
      linagliptin did not influence vessel wall healing, it seems to possess a
      desirable antiproliferative influence on SMCs in vitro and an antiinflammatory
      effect in vivo. These pharmacological properties might carry a potential
      significance for favorable outcome after vascular interventions in diabetic
      patients.

PMID- 27875387
TI  - Clinical Response Rates From Interleukin-2 Therapy for Metastatic Melanoma Over
      30 Years' Experience: A Meta-Analysis of 3312 Patients.
AB  - Interleukin-2 (IL-2), initially used in 1986, can induce clinical regression
      complete responses (CR) and partial responses (PR) of metastatic malignant
      melanoma. IL-2 has been used alone or in combination, and in different dosage
      schedules, as an immunotherapeutic agent for melanoma treatment. This meta
      analysis aimed to document and evaluate the spectrum of reported clinical
      response rates from the combined experience of almost 30 years of IL-2 clinical
      usage. Clinical trials using IL-2 for metastatic melanoma therapy that reported:
      dosage, combinations, study details, definitions and clinical CR, PR, and overall
      response (OR) rates were included. A meta-analysis was conducted using the
      preferred reporting items for systematic reviews and meta-analyses (PRISMA)
      guidelines. In total, 34 studies met inclusion criteria, with 41 separate
      treatment arms. For all IL-2 treatment modalities collectively, the CR rate was
      4.0% [95% confidence interval (CI), 2.8-5.3], PR 12.5% (95% CI, 10.1-15.0), and
      OR 19.7% (95% CI, 15.9-23.5). CR pre-1994 was 2.7% versus 6.1% post-1994. High
      and intermediate-IL-2 dosage showed no CR difference, while low-dose IL-2 showed
      a nonstatistical trend toward an increased CR rate. The highest CR rate resulted
      from IL-2 combined with vaccine at 5.0%. The meta-analysis showed that IL-2
      immunotherapy for advanced metastatic melanoma delivered a CR rate of 4% (range,
      0-23%) across nearly 30 years of clinical studies, with gradual improvement over
      time. The significance is that, contrary to popular belief, the data demonstrated
      that CR rates were similar for intermediate versus high-IL-2 dosing.

PMID- 27875388
TI  - Is vulvovaginal atrophy due to a lack of both estrogens and androgens?
AB  - OBJECTIVE: The aim of this study was to review the preclinical data showing the
      role of both estrogens and androgens in the physiology of the vagina, and, most
      likely, in vulvovaginal atrophy of menopause. METHODS: Mass spectrometry-based
      assays (validated according to the FDA guidelines) for the measurement of sex
      steroids, their precursors, and metabolites were used. In addition to fixation of
      the vagina for morphological examination, histomorphometry, immunocytochemistry,
      immunofluorescence, and quantitative reverse transcription polymerase chain
      reaction were performed. RESULTS: The vaginal epithelium of the animals receiving
      dehydroepiandrosterone (DHEA) was made of large multilayered columnar mucous
      cells showing distended cytoplasmic vacuoles representative of an androgenic
      effect. DHEA also stimulates collagen fiber compactness of the lamina propria
      (second layer)-an effect essentially due to an androgenic effect, whereas
      stimulation by DHEA of the muscularis in the third vaginal layer is approximately
      70% due to the androgenic conversion of DHEA. Stimulation of the surface area of
      the nerve endings, on the contrary, is exclusively androgenic. Vaginal weight
      stimulation by DHEA is about 50% androgenic and 50% estrogenic. CONCLUSIONS:
      Practically all studies on the influence of steroid hormones in the vagina have
      focused on luminal epithelial cells. Since all estrogens and androgens in
      postmenopausal women are made intracellularly and derive from the conversion of
      circulating DHEA, it is of interest to observe from these preclinical data that
      DHEA exerts both estrogenic and androgenic activity in the three layers of the
      vagina, the stimulatory effect on nerve density being 100% androgenic. Taking
      vaginal weight as a global parameter, the stimulatory effect of DHEA in the rat
      vagina is about equally estrogenic and androgenic, thus illustrating the
      importance of androgens in vaginal morphology and function, and the likely
      importance of androgens in vulvovaginal atrophy of menopause.

PMID- 27875390
TI  - Links between reproductive factors and general health.

PMID- 27875393
TI  - Should you witness a signature on a patient's personal legal document?

PMID- 27875389
TI  - Comparative effectiveness of electro-acupuncture versus gabapentin for sleep
      disturbances in breast cancer survivors with hot flashes: a randomized trial.
AB  - OBJECTIVE: Sleep disturbance is a major consequence of hot flashes among breast
      cancer survivors. This study evaluated the effects of electro-acupuncture (EA)
      versus gabapentin (GP) for sleep disturbances among breast cancer survivors
      experiencing daily hot flashes. METHODS: We analyzed data from a randomized
      controlled trial involving 58 breast cancer survivors experiencing bothersome hot
      flashes at least two times per day. Participants were randomly assigned to
      receive 8 weeks of EA or daily GP (total dose of 900 mg/d). The primary outcome
      was change in the total Pittsburgh Sleep Quality Index (PSQI) score between
      groups at week 8. Secondary outcomes include specific PSQI domains. RESULTS: By
      the end of treatment at week 8, the mean reduction in PSQI total score was
      significantly greater in the EA group than the GP group (-2.6 vs -0.8, P =
      0.044). The EA also had improved sleep latency (-0.5 vs 0.1, P = 0.041) and sleep
      efficiency (-0.6 vs 0.0, P = 0.05) compared with the GP group. By week 8, the EA
      group had improved sleep duration, less sleep disturbance, shorter sleep latency,
      decreased daytime dysfunction, improved sleep efficiency, and better sleep
      quality (P < 0.05 for all) compared with baseline, whereas the GP group improved
      in duration and sleep quality only (P < 0.05). CONCLUSIONS: Among women
      experiencing hot flashes, the effects of EA are comparable with GP for improving
      sleep quality, specifically in the areas of sleep latency and efficiency. Larger
      randomized controlled trials with longer follow-ups are needed to confirm this
      preliminary finding.

PMID- 27875394
TI  - Solution-focused nursing in a crisis situation improves patient outcomes.

PMID- 27875397
TI  - Autologous microvascular breast reconstruction: Postoperative strategies to
      improve outcomes.

PMID- 27875395
TI  - Conquering plagiarism in nursing research and authorship.

PMID- 27875398
TI  - Caring for adults with impaired physical mobility.

PMID- 27875399
TI  - When a preceptor needs a mentor.

PMID- 27875400
TI  - Compact state licensure: Take the "fast lane" to nursing practice.

PMID- 27875401
TI  - Ethics, pain, and pay-for-performance.

PMID- 27875402
TI  - Nursing care for adults with ADHD who take stimulants.

PMID- 27875403
TI  - Postoperative neuropathic pain in adults.

PMID- 27875404
TI  - Recognizing staphylococcal scalded skin syndrome.

PMID- 27875405
TI  - On alert for postpartum preeclampsia.

PMID- 27875406
TI  - Online resources for sepsis.

PMID- 27875408
TI  - Diagnosing acute respiratory distress syndrome in resource limited settings: the
      Kigali modification of the Berlin definition.
AB  - PURPOSE OF REVIEW: The acute respiratory distress syndrome (ARDS) was re-defined
      by a panel of experts in Berlin in 2012. Although the Berlin criteria improved
      upon the validity and reliability of the definition, it did not make diagnosis of
      ARDS in resource limited settings possible. Mechanical ventilation, arterial
      blood gas measurements, and chest radiographs are not feasible in many regions of
      the world. In 2014, we proposed and applied the Kigali modification of the Berlin
      definition in a hospital in Rwanda. This review synthesizes literature from the
      last 18 months relevant to the Kigali modification. RECENT FINDINGS: In the last
      18 months, the need for a universally applicable ARDS definition was reinforced
      by advances in supportive care that can be implemented in resource poor settings.
      Research demonstrating the variable impact of positive end expiratory pressure on
      hypoxemia, the validity of using pulse oximetry rather than arterial blood gas to
      categorize hypoxemia, and the accuracy of lung ultrasound support the use of the
      Kigali modification of the Berlin definition. SUMMARY: Studies directly comparing
      the Berlin definition to the Kigali modification are needed. Ongoing clinical
      research on ARDS needs to include low-income countries.

PMID- 27875409
TI  - Extracorporeal membrane oxygenation: beyond rescue therapy for acute respiratory
      distress syndrome?
AB  - PURPOSE OF REVIEW: This article summarizes the results of past and more recent
      series on venovenous extracorporeal membrane oxygenation (VV-ECMO) and discusses
      its potential indications beyond the rescue of patients with lung failure
      refractory to conventional mechanical ventilation. RECENT FINDINGS: Successful VV
      ECMO treatment in patients with extremely severe influenza A(H1N1)-associated
      acute respiratory distress syndrome (ARDS) and positive results of the CESAR
      trial have led to an exponential use of the technology in recent years. Beyond
      its currently accepted indication as a salvage therapy in ARDS patients with
      refractory hypoxemia or unable to tolerate volume-limited strategies, VV-ECMO may
      improve the outcomes of less severe ARDS patients by facilitating lung-protective
      ventilation. SUMMARY: As initiation of VV-ECMO allows significant decrease in
      tidal volume, plateau and driving pressures, which has been associated with
      improved survival in ARDS patients, new trials should evaluate the impact of its
      early initiation in patients with severe but not refractory ARDS.

PMID- 27875410
TI  - Should we use driving pressure to set tidal volume?
AB  - PURPOSE OF REVIEW: Ventilator-induced lung injury (VILI) can occur despite use of
      tidal volume (VT) limited to 6 ml/kg of predicted body weight, especially in
      patients with a smaller aerated compartment (i.e. the baby lung) in which,
      indeed, tidal ventilation takes place. Because respiratory system static
      compliance (CRS) is mostly affected by the volume of the baby lung, the ratio
      VT/CRS (i.e. the driving pressure, DeltaP) may potentially help tailoring
      interventions on VT setting. RECENT FINDINGS: Driving pressure is the ventilatory
      variable most strongly associated with changes in survival and has been shown to
      be the key mediator of the effects of mechanical ventilation on outcome in the
      acute respiratory distress syndrome. Observational data suggest an increased risk
      of death for patients with DeltaP more than 14 cmH2O, but a well tolerated
      threshold for this parameter has yet to be identified. Prone position along with
      simple ventilatory adjustments to facilitate CO2 clearance may help reduce DeltaP
      in isocapnic conditions. The safety and feasibility of low-flow extracorporeal
      CO2 removal in enhancing further reduction in VT and DeltaP are currently being
      investigated. SUMMARY: Driving pressure is a bedside available parameter that may
      help identify patients prone to develop VILI and at increased risk of death. No
      study had prospectively evaluated whether interventions on DeltaP may provide a
      relevant clinical benefit, but it appears physiologically sound to try titrating
      VT to minimize DeltaP, especially when it is higher than 14 cmH2O and when it has
      minimal costs in terms of CO2 clearance.

PMID- 27875411
TI  - Comparing the Effectiveness of Sagittal Balance, Foraminal Stenosis, and
      Preoperative Cord Rotation in Predicting Postoperative C5 Palsy.
AB  - STUDY DESIGN: Retrospective cohort review. OBJECTIVE: To determine whether
      preoperative cord rotation is independently correlated with C5 palsy when
      analyzed alongside measures of sagittal balance and foraminal stenosis. SUMMARY
      OF BACKGROUND DATA: Postoperative C5 palsy is a well-documented complication of
      cervical procedures with a prevalence of 4%-8%. Recent studies have shown a
      correlation with preoperative spinal cord rotation. There have been few studies,
      however, that have examined the role of sagittal balance and foraminal stenosis
      in the development of C5 palsy. METHODS: A total of 77 patients who underwent
      cervical decompression-10 of whom developed C5 palsy-were reviewed. Sagittal
      balance was assessed using curvature angle and curvature index on radiographs and
      magnetic resonance image (MRI). Cord rotation was assessed on axial MRI. C4-C5
      foraminal stenosis was assessed on sagittal MRI using area measurements and a
      grading scale. Demographics and information on surgical approach were gathered
      from chart review. Correlation with C5 palsy was performed by point-biserial,
      chi, and regression analyses. RESULTS: Point-biserial analysis indicated that
      only cord rotation showed significance (P<0.01). There was no statistical
      significance shown with surgical approach, sex, or age. In addition, changes in
      sagittal balance did not correlate with presence of C5 palsy. Logistic regression
      model yielded cord rotation as the only significant independent predictor of C5
      palsy. For every degree of axial cord rotation, the likelihood ratio for
      suffering a C5 palsy was 3.93 (95% confidence interval, 2.01-8.66; P<0.05).
      CONCLUSIONS: This supports the independent capability of preoperative cord
      rotation to predict postoperative C5 palsy. Lack of correlation with measures of
      neuroforaminal stenosis potentially points to mechanisms other than direct
      compression as the etiology. In addition, the lack of correlation with
      postoperative changes in sagittal balance hints that measures of curvature angle
      and curvature index may not be appropriate to accurately predict this
      complication. LEVEL OF EVIDENCE: Level 3.

PMID- 27875412
TI  - Preoperative Mental Health is not Predictive of Patient-reported Outcomes
      Following a Minimally Invasive Lumbar Discectomy.
AB  - STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: To determine if
      preoperative mental health is associated with patient-reported outcomes (PROs)
      following a minimally invasive lumbar discectomy. SUMMARY OF BACKGROUND DATA:
      PROs are commonly used to quantify a patient's perceived health status. Recently,
      mental health has been theorized to directly affect patients' perception of their
      disability and pain after spine surgery. MATERIALS AND METHODS: A registry of
      patients who underwent a primary, single-level minimally invasive lumbar
      discectomy was reviewed. The association between preoperative Short-Form Health
      Survey mental composite score (MCS) and change in PROs [Oswestry Disability
      Index, back and leg visual analog scale (VAS) pain scores] from preoperative to
      postoperative (6-week, 12-week, 6-month) timepoints was assessed using
      multivariate regression controlling for patient demographics and the respective
      preoperative PRO. Patients in the top and bottom quartiles of preoperative MCS
      were compared regarding achievement of minimum clinically important difference
      for each PRO. RESULTS: A total of 110 patients were included in the analysis.
      Better preoperative mental health was associated with lower preoperative
      disability and decreased preoperative back VAS (P<0.05 for each). Higher
      preoperative MCS was also associated with greater improvements in back VAS at 6
      weeks postoperatively (P<0.05). There was no association between preoperative MCS
      and change in any PROs at the 12-week or 6-month postoperative visits. Patients
      in the bottom quartile of preoperative MCS achieved minimum clinically important
      difference in all PROs at similar rates to patients in the top quartile of
      preoperative MCS. CONCLUSIONS: Patients with better preoperative mental health
      scores are more likely to report decreased disability and pain preoperatively.
      However, preoperative mental health was not predictive of changes in long-term
      disability or pain. As a result, patients with a wide range of preoperative
      mental health scores can achieve satisfactory long-term reductions in disability
      and pain levels after a lumbar discectomy. LEVEL OF EVIDENCE: Level IV.

PMID- 27875413
TI  - Obesity as a Risk Factor for Low Back Pain: A Meta-Analysis.
AB  - STUDY DESIGN: A meta-analysis. OBJECTIVE: To update the current knowledge about
      the association between overweight, obesity, and low back pain (LBP) risk, we
      conducted a meta-analysis of published cohort studies. SUMMARY OF BACKGROUND
      DATA: The association between obesity and LBP risk has been the research focus in
      the past decade. However, available data from studies on the association between
      obesity and LBP remains debatable. METHODS: An extensive English language
      literature retrieval regarding the association between overweight, obesity, and
      the risk of LBP incidence was conducted on PubMed and EMBASE databases through
      December 2015. Meta-analysis for all the included literature was performed by
      STATA 12.0 to summarize test performance with Forest plots after a heterogeneity
      test. Moreover, subgroup and sensitivity analyses were performed to examine the
      potential candidate-effect factors. RESULTS: A total of 10 cohort studies
      including 29,748 subjects satisfied the predefined eligibility criteria. The
      pooled odds ratio (OR) for overweight and obesity compared with normal weight was
      1.15 [95% confidence interval (CI), 1.08-1.21) and 1.36 (95% CI, 1.18-1.57),
      respectively. Moreover, subgroup analysis proved that increased body mass index
      was associated with an increased incidence of LBP in both men (overweight: pooled
      OR=1.16, 95% CI, 1.04-1.31; obesity: pooled OR=1.36, 95% CI, 1.15-1.61) and women
      (overweight: pooled OR=1.24, 95% CI, 1.04-1.50; obesity: pooled OR=1.40, 95% CI,
      1.08-1.82). There was no evidence of publication bias. CONCLUSIONS: Our findings
      consistently show that overweight and obesity are risk factors for LBP in men and
      women. Maintaining a healthy body weight may be one of the factors preventing the
      occurrence of LBP. LEVEL OF EVIDENCE: Level 1.

PMID- 27875414
TI  - The Influence of Histologic Subtype in Predicting Survival of Lung Cancer
      Patients With Spinal Metastases.
AB  - STUDY DESIGN: Retrospective analysis. SUMMARY OF BACKGROUND DATA: Recent
      advancements in systemic treatment of lung cancer have significantly improved the
      survival of patients with certain histolopathologic and molecular subtypes.
      Existing prognostic scores do not account for this and patients with lung cancer
      spinal metastases are grouped together as poor prognostic candidates, and
      consequently, some may be inappropriately denied palliative spine surgery.
      OBJECTIVE: The objective of the study was to study whether the expected survival
      in patients with lung cancer spinal metastases is affected by histolopathologic
      and molecular subtypes in the context of modern systemic therapy. MATERIALS AND
      METHODS: We retrospectively reviewed all patients with histologically confirmed
      lung cancer treated for spinal metastases at our institution between 2001 and
      2012. Patients' demographics, histopathologic details, treatment modalities, and
      survival data were collected. The primary outcome was survival from time of
      spinal metastases diagnosis. The Cox regression analysis was used to evaluate the
      influence of tumor histology, molecular profile and treatment modality on
      survival. The Kaplan-Meier survival analysis was conducted to compare lung cancer
      subtypes, as well as various treatment regimens. RESULTS: Out of 180 patients, 51
      underwent surgery for spinal metastases. Female sex (P=0.019), absence of palsy
      (P=0.023), good Karnofsky performance scores (P<0.001), and non-small cell lung
      cancer (NSCLC) (P=0.002) were favorable prognostic factors. Patients who received
      systemic therapy, including tyrosine kinase inhibitors, platinum doublet
      chemotherapy, or both showed increased survival (P<0.01). The median survival
      time was 2.40 months [95% confidence interval (CI), 2.13-2.68] in the small cell
      lung cancer cohort, with no patients surviving past a year; 5.10 months (95% CI,
      3.78-6.41) in the NSCLC cohort, with 25.9% 1-year survival; and 13.3 months (95%
      CI, 2.26-24.40) in adenocarcinoma patients who received both tyrosine kinase
      inhibitors and platinum doublet therapy, with 50.0% 1-year survival. CONCLUSIONS:
      NSCLC, systemic therapy, female sex, absence of palsy and good Karnofsky
      performance scores are all independent favorable prognostic factors for patients
      with lung cancer spinal metastases. These should be routinely considered during
      prognostication.

PMID- 27875415
TI  - A Posterior Oblique Approach to the Lumbar Disk Spaces, Vertebral Bodies, and
      Lumbar Plexus: A Cadaveric Feasibility Study.
AB  - STUDY DESIGN: A laboratory cadaveric study. OBJECTIVE: We aimed to demonstrate
      the feasibility of a posterior oblique approach, sharing the same advantages as
      the transpsoas technique while minimizing the risk of lumbar plexus or psoas
      muscle injuries. SUMMARY OF BACKGROUND DATA: The transpsoas approach for
      interbody fusion and corpectomy offers advantages over posterior and anterior
      approaches. However, possible risks include traumatization of the psoas muscle or
      lumbar plexus. METHODS: All lumbar disk spaces and vertebral bodies were exposed
      by a posterior oblique approach from left and right on a human cadaveric
      specimen. The exposure obtained and a step-by-step documentation of the procedure
      is outlined in detail. RESULTS: We were able to achieve wide exposure of all
      lumbar disk spaces and vertebral bodies above the L5/S1 disk space. Only the
      psoas muscle was retracted, and the lumbar plexus nerves were easily visualized
      and gently retracted. Sharp dissection was only required around the tip of the
      transverse processes. CONCLUSIONS: A posterior oblique approach seems to be less
      invasive than the transpsoas approach. Exposure of the anterior column structures
      above the iliac crest is comparable. The oblique approach offers direct access to
      the lumbar plexus and the extraforaminal segments of the nerve roots.

PMID- 27875416
TI  - Comparison of Structural Disease Burden to Health-related Quality of Life Scores
      in 264 Adult Spinal Deformity Patients With 2-Year Follow-up: Novel Insights into
      Drivers of Disability.
AB  - STUDY DESIGN: This is a review of a prospective multicenter database. OBJECTIVE:
      To investigate the relationship between preoperative disability and sagittal
      deformity in patients with high Oswestry Disability Index (ODI) and no sagittal
      malalignment, or low ODI and high sagittal malalignment. SUMMARY OF BACKGROUND
      DATA: The relationship between ODI and sagittal malalignment varies between each
      adult spinal deformity (ASD) patient. METHODS: A prospective multicenter database
      of 365 patients with ASD undergoing surgical reconstruction was analyzed.
      Inclusion criteria entailed: age 18 years or above and the presence of spinal
      deformity as defined by a coronal Cobb angle>=20 degrees, sagittal vertical axis
      (SVA)>=5 cm, pelvic tilt (PT) angle>=25 degrees, or thoracic kyphosis>=60
      degrees. Radiographic and health-related quality of life (HRQOL) variables were
      examined and compared, preoperatively and at 2-year postoperative follow-up.
      Group 1 (low disability high sagittal-LDHS) consisted of ODI<40 and SVA>=5 cm or
      PT>=25 degrees or pelvic incidence-lumbar lordosis>=11 degrees and group 2 (high
      disability low sagittal-HDLS) consisted of ODI>40 and SVA<5 cm and PT<25 degrees
      and pelvic incidence-lumbar lordosis<11 degrees. RESULTS: Of 264 patients with
      follow-up, 58 (22.0%) patients were included in LDHS and 30 (11.4%) were included
      in HDLS. Both groups had similar demographics and preoperative coronal angles.
      HDLS had worse baseline HRQOL for all measures (P<0.05) except leg and back pain.
      HDLS had a higher rate of self-reported leg weakness, arthritis, depression and
      neurological disorder. Both groups had similar 2-year improvements in HRQOL
      (P>0.05), except only HDLS had a significant Scoliosis Research Society Mental
      improvement and a significantly higher rate of reaching minimal clinically
      important differences in Scoliosis Research Society Mental scores (P<0.05).
      CONCLUSIONS: There is an association of worse baseline HRQOL measures, weakness,
      arthritis, and mental disease in HDLS. Furthermore, HDLS patients demonstrated
      similar improvements to LDHS. However, HDLS had greater improvements in the
      mental domains, perhaps indicating the responsiveness of the mental disability to
      surgical treatment. LEVEL OF EVIDENCE: Level III.

PMID- 27875417
TI  - The Utility of Routinely Obtaining Postoperative Laboratory Studies Following a
      Minimally Invasive Transforaminal Lumbar Interbody Fusion.
AB  - STUDY DESIGN: This is a retrospective analysis. OBJECTIVE: To test the hypothesis
      that there is limited utility in routinely obtaining postoperative laboratory
      values following minimally invasive transforaminal lumbar interbody fusion (MIS
      TLIF). BACKGROUND DATA: At many institutions, it is routine to obtain a complete
      blood count and basic metabolic profile (BMP) following a MIS TLIF. However, the
      utility of this practice has not been well characterized. METHODS: A total of 332
      consecutive patients who underwent a primary, 1-level MIS TLIF for degenerative
      spinal pathology between 2007 and 2013 were identified. Patients were stratified
      into low-risk and high-risk cohorts based upon risk for postoperative laboratory
      abnormalities. Inclusion criteria for the high-risk cohort were malignancy,
      complicated diabetes, renal failure, liver disease, hematologic disease, or
      significant intraoperative blood loss (>300 mL). Preoperative and postoperative
      hemoglobin (Hb), hematocrit, and BMP values were compared. Any interventions that
      were potentially related to laboratory values were identified. RESULTS: Totals of
      270 low-risk and 62 high-risk patients were identified. Mean postoperative Hb,
      hematocrit, blood urea nitrogen, sodium, potassium, and calcium values were
      decreased compared with preoperative values (P<0.001 for each) in both cohorts.
      Similar changes from preoperative levels were demonstrated in each cohort. No
      patients received blood product transfusion. Eleven low-risk (4.1%) and 5 high
      risk patients (8.1%) received oral potassium supplementation. All patients who
      received potassium supplementation were asymptomatic. Most patients who were
      given potassium replacement consumed medications known to decrease serum
      potassium levels. No other interventions were performed in either group.
      CONCLUSIONS: Despite a significant decrease in mean Hb concentration following
      surgery, no patients required a transfusion. In total, 16 patients received
      potassium supplementation likely related to medication-related potassium
      deficits. Overall, these findings suggest that the utility of routinely obtaining
      a complete blood count or BMP following uncomplicated MIS TLIF may be limited
      except in the setting of select preoperative comorbidities and/or perioperative
      risk factors or events. LEVEL OF EVIDENCE: Level III.

PMID- 27875418
TI  - Nonclassic features of pseudohypoparathyroidism type 1A.
AB  - PURPOSE OF REVIEW: To provide readers with a review of contemporary literature
      describing the evolving understanding of the pseudohypoparathyroidism type 1A
      (PHP1A) phenotype. RECENT FINDINGS: The classic features of PHP1A include
      multihormone resistance and the Albright Hereditary Osteodystrophy phenotype
      (round facies, short stature, subcutaneous ossifications, brachydactyly, and
      early-onset obesity. Obesity may be because of a decrease in resting energy
      expenditure because most patients do not report significant hyperphagia. Patients
      with PHP1A have an increased risk of type 2 diabetes. In addition to
      brachydactyly and short stature, orthopedic complications can include spinal
      stenosis and carpal tunnel syndrome. Hearing loss, both sensorineural and
      conductive, has been reported in PHP1A. In addition, ear-nose-throat findings
      include decreased olfaction and frequent otitis media requiring tympanostomy
      tubes. Sleep apnea was shown to be 4.4-fold more common in children with PHP1A
      compared with other obese children; furthermore, asthma-like symptoms have been
      reported. These new findings are likely multifactorial and further research is
      needed to better understand these nonclassic features of PHP1A. SUMMARY: Along
      with the Albright Hereditary Osteodystrophy phenotype and hormone resistance,
      patients with PHP1A may have additional skeletal, metabolic, ear-nose-throat, and
      pulmonary complications. Understanding these nonclassic features will help
      improve clinical care of patients with PHP1A.

PMID- 27875419
TI  - New treatment options for irritable bowel syndrome with predominant diarrhea.
AB  - PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a highly prevalent
      gastrointestinal disorder with negative impact on quality of life and it
      represents a substantial economic burden on healthcare cost. The medical
      management of IBS remains largely symptomatic. This review provides an update
      related to the most recently published diagnostic Rome IV criteria for IBS and
      clinical trial data for novel treatment modalities in IBS targeting the
      peripheral opioid receptors of the enteric nervous system and the gut microbiota.
      RECENT FINDINGS: The new Rome IV criteria define functional gastrointestinal
      disorders as disorders of the gut-brain interaction. In addition to previously
      introduced pharmacological treatment modalities for IBS with constipation (IBS-C)
      with synthetic peptides and small molecules targeting gastrointestinal receptors
      and ion channels, the newly Food and Drug Administration-approved mixed
      peripheral opioid receptor agonist/antagonist eluxadoline and the nonabsorbable
      antibiotic rifaximin demonstrate efficacy and safety in the treatment of IBS with
      predominant diarrhea (IBS-D). SUMMARY: Diagnostic criteria for functional
      gastrointestinal disorders, including IBS, have been revised in Rome IV and are
      defined as gut-brain disorders. The mixed peripheral opioid receptor
      agonist/antagonist eluxadoline and the antibiotic rifaximin have been recently
      Food and Drug Administration approved for the treatment of diarrhea-predominant
      IBS (IBS-D) with proven efficacy and acceptable side-effect profiles.

PMID- 27875421
TI  - Taking Care of Business.
AB  - Here's to those who quietly go about doing their important work.

PMID- 27875423
TI  - Telemedicine.

PMID- 27875422
TI  - Helping Patients and Families Understand the Financial Impact of End-of-Life
      Care.
AB  - Planning ahead is crucial-nurses can provide information and resources.

PMID- 27875424
TI  - Nurses and Policy Positions.

PMID- 27875425
TI  - Nurse Fatigue.

PMID- 27875420
TI  - Molecular imaging in neuroendocrine tumors: recent advances, controversies,
      unresolved issues, and roles in management.
AB  - PURPOSE OF REVIEW: The purpose is to review recent advances in molecular imaging
      of neuroendocrine tumors (NETs), discuss unresolved issues, and review how these
      advances are affecting clinical management. RECENT FINDINGS: Molecular imaging of
      NETs underwent a number of important changes in the last few years, leading to
      some controversies, unresolved issues, and significant changes in clinical
      management. The most recent changes are reviewed in this article. Particularly
      important is the rapid replacement in somatostatin receptor scintigraphy of In
      diethylenetriamine penta-acetic acid-single-photon emission computed
      tomography/computed tomography (CT) by Ga-fluorodopa(F-D)PA), 1,4,7,10
      tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptide-PET/CT imaging,
      which is now approved in many countries including the USA. Numerous studies in
      many different types of NETs demonstrate the greater sensitivity of Ga-DOTA
      peptide PET/CT, its high specificity, and its impact on management. Other
      important developments in somatostatin receptor scintigraphy/molecular imaging
      include demonstrating the prognostic value of both Ga-DOTA-peptide PET/CT and F
      fluoro-deoxyglucose PET/CT; how their use can be complementary; comparing the
      sensitivities and usefulness of Ga-DOTA-peptide PET/CT and F-FDOPA PET/CT;
      introducing new linkers and radiolabeled ligands such as Cu-DOTA-peptides with a
      long half-life, enhancing utility; and the introduction of somatostatin receptor
      antagonists which show enhanced uptake by NETs. In addition, novel ligands which
      interact with other receptors (GLP-1, bombesin, cholecystokinin, gastric
      inhibitory polpeptide, integrin, chemokines) are described, which show promise in
      the imaging of both NETs and other tumors. SUMMARY: Molecular imaging is now
      required for all aspects of the management of patients with NETs. Its results are
      essential not only for the proper diagnostic management of the patient, but also
      for assessing whether the patient is a candidate for peptide receptor
      radionuclide therapy with Lu and also for providing prognostic value.

PMID- 27875426
TI  - The High Cost of Prescription Drugs in America.
AB  - Recent controversies are shedding light on the complex-and sometimes unsavory
      forces at work.

PMID- 27875427
TI  - New Patient Safety Requirements Toughen Nurse Licensure Compact.
AB  - Changes include mandatory criminal background checks.

PMID- 27875428
TI  - Physical Restraint Use Associated with RN Staffing.
AB  - Adding non-RN nursing staff when patient load fluctuates doesn't check restraint
      use.

PMID- 27875429
TI  - NewsCAP: Cognitive behavioral therapy is as effective as antidepressants for
      depressive disorder.

PMID- 27875430
TI  - NewsCAP: Maine ends grant to treat teens and young adults with mental illness.

PMID- 27875431
TI  - Do Infant Simulators Deter Teen Pregnancy?
AB  - Study shows girls who took simulators home had higher subsequent pregnancy rates.

PMID- 27875433
TI  - Parents Often Give the Wrong Dose of Medication to Their Children.
AB  - Using oral syringes may reduce errors.

PMID- 27875435
TI  - UK Nurse Infected with Ebola Cleared of Misconduct.

PMID- 27875436
TI  - Nurse Suicides Spur Protests in France.

PMID- 27875439
TI  - As Spending Skyrockets for Direct-to-Consumer Prescription Drug Ads, So Does
      Pushback.
AB  - Arguments center on harm vs. benefit to patients and providers.

PMID- 27875442
TI  - OTC Antacids Containing Aspirin Carry Risk of Bleeding.

PMID- 27875443
TI  - FDA Strengthens Warning Concerning Coadministration of Opioids and
      Benzodiazepines.

PMID- 27875445
TI  - 2 CE Test Hours: Original Research: Examining the Links Between Lifestyle Factors
      and Metabolic Syndrome.

PMID- 27875446
TI  - 2 CE Test Hours: Preventing Contrast-Induced Acute Kidney Injury.

PMID- 27875447
TI  - Remembering Pearl Harbor at 75 Years.
AB  - : On December 7, 1941, the Sunday-morning quiet of the U.S. naval base in Pearl
      Harbor, Hawaii, was shattered by dive-bombing Japanese fighter planes. The planes
      came in two waves-and when it was all over, more than 2,400 were killed and more
      than 1,100 were injured.Nurses were stationed at U.S. Naval Hospital Pearl
      Harbor, Tripler General Hospital (now Tripler Army Medical Center), Hickam Field
      Hospital, Schofield Barracks Station Hospital, and aboard the USS Solace, and
      witnessed the devastation. But they also did what nurses do in emergencies-they
      responded and provided care to those in need. Here are the stories of a few of
      those nurses.

PMID- 27875448
TI  - Administration of Subcutaneous Injections.
AB  - This article is the second in a series, Supporting Family Caregivers: No Longer
      Home Alone, published in collaboration with the AARP Public Policy Institute.
      Results of focus groups conducted as part of the AARP Public Policy Institute's
      No Longer Home Alone video project supported evidence that family caregivers
      aren't being given the information they need to manage the complex care regimens
      of their family members. This series of articles and accompanying videos aims to
      help nurses provide caregivers with the tools they need to manage their family
      member's medications. Each article explains the principles nurses should consider
      and reinforce with caregivers and is accompanied by a video for the caregiver to
      watch. The second video can be accessed at http://links.lww.com/AJN/A75.

PMID- 27875449
TI  - Year-End Reindeer Dreams.
AB  - Updated several times a week with posts by a wide variety of authors, AJN's blog
      Off the Charts allows us to provide more timely-and often more personal
      perspectives on professional, policy, and clinical issues. Best of the Blog will
      be a regular column to bring AJN readers recent posts that we think deserve a
      wider audience. To read more, please visit: www.ajnoffthecharts.com.

PMID- 27875450
TI  - Student Nurse in the War Zone.
AB  - : Editor's note: From its first issue in 1900 through to the present day, AJN has
      unparalleled archives detailing nurses' work and lives over more than a century.
      These articles not only chronicle nursing's growth as a profession within the
      context of the events of the day, but they also reveal prevailing societal
      attitudes about women, health care, and human rights. Today's nursing school
      curricula rarely include nursing's history, but it's a history worth knowing. To
      this end, From the AJN Archives highlights articles selected to fit today's
      topics and times.In this month's article, from the September 1942 issue, senior
      nursing student Frances Carr writes vividly about life and work in Honolulu after
      Pearl Harbor. "Students... have had seared into their memories scenes of such
      horror as cannot be imagined.... When night fell, the nursing staff faced its
      first test of caring for hundreds of patients in a blackout that had to be
      absolute." And in this issue, see "Remembering Pearl Harbor at 75 Years," which
      tells the stories of five nurses from the Army and Navy Nurse Corps who were
      stationed nearby at the time of the attack.

PMID- 27875451
TI  - Developing a Framework to Help Bedside Nurses Bring About Change.
AB  - : Nurses across all care settings and experience levels are being called upon to
      lead. In a 2011 report, The Future of Nursing: Leading Change, Advancing Health,
      the Institute of Medicine examined the ways nurses could more fully apply their
      knowledge of direct patient care to address the increasing demands placed on the
      health care system since the passage of the Affordable Care Act. The report
      asked: "What roles can nursing assume to address the increasing demand for safe,
      high-quality, and effective health care services?"Multiple variables influence a
      nurse's ability to assume a leadership role, and multiple barriers to these roles
      continue to exist. This article uses the first-person voice to share the
      experience of a new graduate nurse in a formal nurse residency program who found
      himself in a position to identify the need for, advocate for, and ultimately
      influence a policy change in the staffing practice of floating as it was applied
      to new RNs on his unit. In a retrospective analysis of the process, the new
      graduate RN and his former professor acting as a writing mentor developed a
      leadership framework for nurses called RN LEADER, which they hope will empower
      and guide other nurses to lead evidence-based change in their workplaces.

PMID- 27875452
TI  - Celebrating Nursing Science.
AB  - Nurse researchers gather in Washington, DC, to highlight new research and future
      areas of study.

PMID- 27875453
TI  - Integrating Mental Health into Primary Care.
AB  - As part of its Raise the Voice campaign to showcase nurses who are key players in
      transforming health care, the American Academy of Nursing has identified nurses
      they call edge runners-"practical innovators who have led the way in bringing new
      thinking and new methods to a wide range of health care challenges." This is the
      seventh in AJN's series of profiles of these nursing innovators. Read and be
      proud of what nurses can accomplish.

PMID- 27875455
TI  - Sitting with Death.
AB  - A social worker on a dialysis unit bears witness to patients' life or death
      choices.

PMID- 27875456
TI  - Reduction in the Cesarean Delivery Rate After Obstetric Care Consensus Guideline
      Implementation.

PMID- 27875457
TI  - In Reply.

PMID- 27875458
TI  - All-Cause and Cause-Specific Mortality After Hypertensive Disease of Pregnancy.

PMID- 27875459
TI  - In Reply.

PMID- 27875460
TI  - Insect Repellants During Pregnancy in the Era of the Zika Virus.

PMID- 27875461
TI  - In Reply.

PMID- 27875463
TI  - In Reply.

PMID- 27875462
TI  - Obstetric Forceps: A Species on the Brink of Extinction andForceps, Simulation,
      and Social Media andSimulation Training for Forceps-Assisted Vaginal Delivery and
      Rates of Maternal Perineal Trauma.

PMID- 27875464
TI  - In Reply.

PMID- 27875469
TI  - Practice Bulletin No. 175 Summary: Ultrasound in Pregnancy.
AB  - Obstetric ultrasonography is an important and common part of obstetric care in
      the United States. The purpose of this document is to present information and
      evidence regarding the methodology of, indications for, benefits of, and risks
      associated with obstetric ultrasonography in specific clinical situations.
      Portions of this Practice Bulletin were developed from collaborative documents
      with the American College of Radiology and the American Institute of Ultrasound
      in Medicine (1, 2).

PMID- 27875470
TI  - Committee Opinion No. 681 Summary: Disclosure and Discussion of Adverse Events.
AB  - Adverse outcomes, preventable or otherwise, are a reality of medical care. Most
      importantly, adverse events affect patients, but they also affect health care
      practitioners. Disclosing information about adverse events has benefits for the
      patient and the physician and, ideally, strengthens the patient-physician
      relationship and promotes trust. Studies show that after an adverse outcome,
      patients expect and want timely and full disclosure of the event, an
      acknowledgment of responsibility, an understanding of what happened, expressions
      of sympathy, and a discussion of what is being done to prevent recurrence.
      Surveys have shown that patients are less likely to pursue litigation if they
      perceive that the event was honestly disclosed. Barriers to full disclosure are
      many and include fear of retribution for reporting an adverse event, lack of
      training, a culture of blame, and fear of lawsuits. To reduce these concerns, it
      is recommended that health care facilities establish a nonpunitive, blame-free
      culture that encourages staff to report adverse events and near misses (close
      calls) without fear of retaliation. Health care institutions should have written
      policies that address the management of adverse events. Having a responsive
      process to inform and aid the patient, loved ones, and practitioners is required.
      A commitment on the part of all health care practitioners and institutions to
      establish programs and develop the tools needed to help patients, families,
      health care practitioners, and staff members deal with adversity is essential.

PMID- 27875471
TI  - Committee Opinion No. 682 Summary: Microarrays and Next-Generation Sequencing
      Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and
      Gynecology.
AB  - Genetic technology has advanced dramatically in the past few decades, and its
      applications and use in caring for and counseling pregnant women has been
      transformational in the realm of prenatal diagnosis. Two of the newer genetic
      technologies in the prenatal setting are chromosomal microarray and whole-exome
      sequencing. Chromosomal microarray analysis is a method of measuring gains and
      losses of DNA throughout the human genome. It can identify chromosomal aneuploidy
      and other large changes in the structure of chromosomes as well as submicroscopic
      abnormalities that are too small to be detected by traditional modalities.
      Prenatal chromosomal microarray analysis is recommended for a patient with a
      fetus with one or more major structural abnormalities identified on
      ultrasonographic examination and who is undergoing invasive prenatal diagnosis.
      Whole-genome sequencing analyzes the entire genome, including noncoding regions
      (introns) and coding regions (exons). However, because the introns are typically
      of little clinical relevance, there has been a focus instead on whole-exome
      sequencing, which examines the coding regions (exons) of the genome. The exons
      generally have greater clinical relevance and applicability to patient care.
      However, the routine use of whole-genome or whole-exome sequencing for prenatal
      diagnosis is not recommended outside of the context of clinical trials.

PMID- 27875472
TI  - Practice Bulletin No. 175: Ultrasound in Pregnancy.

PMID- 27875473
TI  - Committee Opinion No. 681: Disclosure and Discussion of Adverse Events.
AB  - Adverse outcomes, preventable or otherwise, are a reality of medical care. Most
      importantly, adverse events affect patients, but they also affect health care
      practitioners. Disclosing information about adverse events has benefits for the
      patient and the physician and, ideally, strengthens the patient-physician
      relationship and promotes trust. Studies show that after an adverse outcome,
      patients expect and want timely and full disclosure of the event, an
      acknowledgment of responsibility, an understanding of what happened, expressions
      of sympathy, and a discussion of what is being done to prevent recurrence.
      Surveys have shown that patients are less likely to pursue litigation if they
      perceive that the event was honestly disclosed. Barriers to full disclosure are
      many and include fear of retribution for reporting an adverse event, lack of
      training, a culture of blame, and fear of lawsuits. To reduce these concerns, it
      is recommended that health care facilities establish a nonpunitive, blame-free
      culture that encourages staff to report adverse events and near misses (close
      calls) without fear of retaliation. Health care institutions should have written
      policies that address the management of adverse events. Having a responsive
      process to inform and aid the patient, loved ones, and practitioners is required.
      A commitment on the part of all health care practitioners and institutions to
      establish programs and develop the tools needed to help patients, families,
      health care practitioners, and staff members deal with adversity is essential.

PMID- 27875474
TI  - Committee Opinion No.682: Microarrays and Next-Generation Sequencing Technology:
      The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology.
AB  - Genetic technology has advanced dramatically in the past few decades, and its
      applications and use in caring for and counseling pregnant women has been
      transformational in the realm of prenatal diagnosis. Two of the newer genetic
      technologies in the prenatal setting are chromosomal microarray and whole-exome
      sequencing. Chromosomal microarray analysis is a method of measuring gains and
      losses of DNA throughout the human genome. It can identify chromosomal aneuploidy
      and other large changes in the structure of chromosomes as well as submicroscopic
      abnormalities that are too small to be detected by traditional modalities.
      Prenatal chromosomal microarray analysis is recommended for a patient with a
      fetus with one or more major structural abnormalities identified on
      ultrasonographic examination and who is undergoing invasive prenatal diagnosis.
      Whole-genome sequencing analyzes the entire genome, including noncoding regions
      (introns) and coding regions (exons). However, because the introns are typically
      of little clinical relevance, there has been a focus instead on whole-exome
      sequencing, which examines the coding regions (exons) of the genome. The exons
      generally have greater clinical relevance and applicability to patient care.
      However, the routine use of whole-genome or whole-exome sequencing for prenatal
      diagnosis is not recommended outside of the context of clinical trials.

PMID- 27875475
TI  - Scar-based catheter ablation for persistent atrial fibrillation.
AB  - PURPOSE OF REVIEW: Percutaneous catheter ablation can be an effective treatment
      for paroxysmal atrial fibrillation. However, catheter ablation for the treatment
      of persistent atrial fibrillation or long-standing persistent atrial fibrillation
      is associated with success rates of 45-50% at 1 year. To address the challenge of
      ablating patients with persistent atrial fibrillation, several approaches have
      been proposed. Atrial scar-based catheter ablation is a promising strategy for
      ablation of persistent atrial fibrillation. RECENT FINDINGS: In this review, we
      outline the role of atrial scar/fibrosis in the pathophysiology of atrial
      fibrillation and how this encouraged clinical studies assessing the atrial
      substrate using scar-based mapping. We highlight current approaches to voltage
      mapping of atrial scar in patients with atrial fibrillation. The characteristics,
      techniques, and outcomes of recently published studies evaluating scar-based
      catheter ablation strategies for the treatment of atrial fibrillation are
      discussed. Finally, we explore the role of noninvasive tools such as delayed
      enhancement MRI to assess the atrial fibrillation substrate. SUMMARY: In summary,
      the optimal catheter ablation strategy for persistent atrial fibrillation remains
      unknown. Current data highlight the need for a better understanding of the
      substrate and mechanisms of arrhythmia maintenance in this population. Atrial
      scar-based catheter ablation has recently emerged as a promising strategy for
      ablation of atrial fibrillation. However, the available data have limitations
      that preclude definitive conclusions regarding the utility of this strategy.
      Further research is needed to assess the role of scar-based ablation for
      persistent atrial fibrillation.

PMID- 27875476
TI  - Pacing to prevent atrial fibrillation.
AB  - PURPOSE OF REVIEW: Pacemakers are frequently implanted in patients with atrial
      fibrillation. Many patients with pacemakers also develop atrial fibrillation.
      Over a period of time, through many studies on different pacing modes, sites, and
      algorithms, significant insights have been gained in the field of treatment and
      prevention of atrial fibrillation. The purpose of this review is to discuss some
      aspects of the scientific basis, current standards and possible future research
      related to cardiac pacing for prevention of atrial fibrillation. RECENT FINDINGS:
      Trials involving pacing at the alternative pacing site per se or in combination
      with specific algorithms for prevention of atrial fibrillation have not shown
      consistent results. Recently, a new generation of antitachycardia pacing
      therapies has brought on a new optimism with promising outcome data of reduction
      in permanent atrial fibrillation, cardiovascular hospitalizations, and mortality.
      SUMMARY: Multiple trials and clinical observational studies of different pacing
      methods and algorithms, with the exception of newer therapies in conjunction with
      atrial pacing algorithms, have not been shown to prevent atrial fibrillation.
      Hence, while permanent pacing is indicated for sinus node dysfunction and
      conduction abnormalities in patients with or without atrial fibrillation, the
      prevailing data in the literature does not support implantation of a permanent
      pacemaker for prevention of atrial fibrillation per se.

PMID- 27875477
TI  - Smartphone-based arrhythmia monitoring.
AB  - The use of smartphones for arrhythmia monitoring is another leap for ECG
      utilization and arrhythmia detection - effectively taking the technology to any
      smartphone user. Smart wearable technology, while very common, is limited mostly
      to activity tracking and exercise motivation. Rhythm strip generating smartphone
      products (Kardia Mobile by AliveCor and ECG Check by Cardiac Designs) are more
      powerful at arrhythmia detection than wearable monitors. These products, which
      have been studied in a variety of situations, rely on an external device with
      metal sensors to create a rhythm strip, which is usually Lead I. A different
      subset of smartphone products use photoplethysmography through a phone camera and
      light to detect atrial fibrillation. Together, these products are creating a
      paradigm shift in rhythm detection and monitoring.

PMID- 27875478
TI  - Functional mitral stenosis following mitral valve repair.
AB  - PURPOSE OF REVIEW: This review summarizes the evidence describing functional
      mitral stenosis (MS) following surgical mitral valve repair. RECENT FINDINGS:
      Functional MS is an evolving concept and has been implicated in the repair of
      functional and organic mitral regurgitation. Following repair of functional
      mitral regurgitation, an elevation in peak transmitral gradient and pulmonary
      artery pressure has been observed under physiologic stress. These changes have
      been associated with worse functional status early after restrictive
      annuloplasty. Following repair of organic mitral regurgitation, functional MS has
      also been observed and appears associated with worse functional status late after
      surgery. SUMMARY: Because repair of functional mitral regurgitation commonly
      involves restrictive annuloplasty, the issue of functional MS must be weighed
      against the benefits and durability of repair. Functional MS following repair of
      degenerative mitral regurgitation, however, may be modifiable. Research
      evaluating various repair techniques and their impact on functional MS following
      repair of organic is ongoing.

PMID- 27875479
TI  - Development and validation of a short-form Pain Medication Attitudes
      Questionnaire (PMAQ-14).
AB  - Attitudes to pain medication are important aspects of adjustment to chronic pain.
      They are measured by the 47-item Pain Medication Attitudes Questionnaire (PMAQ).
      To measure those attitudes more quickly and easily, we developed and evaluated a
      14-item PMAQ using data from 3 separate surveys of people with pain in the
      general population. In survey 1, participants (n = 295) completed the 47-item
      PMAQ and measures of pain, analgesic use, analgesic dependence, and attitudes to
      self-medication. For each of the 7 PMAQ scales, the 2 items that best preserved
      the content of the full parent scales were identified using correlation and
      regression. The 2-item and full parent scales had very similar relationships with
      other measures, indicating that validity had been maintained. The resulting 14
      item PMAQ was then completed by participants in survey 2 (n = 241) and survey 3
      (n = 147), along with the same other measures as in survey 1. Confirmatory factor
      analysis showed that the 14-item PMAQ retained the 7-factor structure of the 47
      item version, and correlations with other measures showed that it retained the
      validity of the 47-item version. The PMAQ scale Need was the most significant
      independent predictor of analgesic dependence in each of 4 separate multiple
      regression analyses. This short form of the PMAQ allows attitudes to pain
      medications to be measured in a valid and more efficient way.

PMID- 27875480
TI  - Innovative treatments for back pain.

PMID- 27875483
TI  - Intraoperative Blood Pressure Discrepancy Between Arms During Prone Position!

PMID- 27875481
TI  - Receipt of Caregiving and Fall Risk in US Community-dwelling Older Adults.
AB  - BACKGROUND: Falls and fall-related injuries (FRI) are common and costly
      occurrences among older adults living in the community, with increased risk for
      those with physical and cognitive limitations. Caregivers provide support for
      older adults with physical functioning limitations, which are associated with
      fall risk. DESIGN: Using the 2004-2012 waves of the Health and Retirement Study,
      we examined whether receipt of low (0-13 weekly hours) and high levels (>=14
      weekly hours) of informal care or any formal care is associated with lower risk
      of falls and FRIs among community-dwelling older adults. We additionally tested
      whether serious physical functioning (>=3 activities of daily living) or
      cognitive limitations moderated this relationship. RESULTS: Caregiving receipt
      categories were jointly significant in predicting noninjurious falls (P=0.03) but
      not FRIs (P=0.30). High levels of informal care category (P=0.001) and formal
      care (P<0.001) had stronger associations with reduced fall risk relative to low
      levels of informal care. Among individuals with >=3 activities of daily living,
      fall risks were reduced by 21% for those receiving high levels of informal care;
      additionally, FRIs were reduced by 42% and 58% for those receiving high levels of
      informal care and any formal care. High levels of informal care receipt were also
      associated with a 54% FRI risk reduction among the cognitively impaired.
      CONCLUSIONS: Fall risk reductions among older adults occurred predominantly among
      those with significant physical and cognitive limitations. Accordingly, policy
      efforts involving fall prevention should target populations with increased
      physical functioning and cognitive limitations. They should also reduce financial
      barriers to informal and formal caregiving.

PMID- 27875482
TI  - Impact of Community Health Workers on Elderly Patients' Advance Care Planning and
      Health Care Utilization: Moving the Dial.
AB  - BACKGROUND: Advance care planning (ACP) is recommended for all persons to ensure
      that the care they receive aligns with their values and preferences. OBJECTIVE:
      To evaluate an ACP intervention developed to better meet the needs and priorities
      of persons with chronic diseases, including mild cognitive impairment. RESEARCH
      DESIGN: A year-long, pre-post intervention using lay community health workers
      [care coordinator assistants (CCAs)] trained to conduct and document ACP
      conversations with patients during home health visits with pre-post evaluation.
      SUBJECTS: The 818 patients were 74.2 years old (mean); 78% women; 51% African
      American; 43% white. MEASURES: Documentation of ACP conversation in electronic
      health record fields and health care utilization outcomes. RESULTS: In this
      target population ACP documentation rose from 3.4% (pre-CCA training) to 47.9%
      (post) of patients who had at least 1 discussion about ACP in the electronic
      health record. In the 1-year preintervention period, there were no differences in
      admissions, emergency department (ED) visits, and outpatient visits between
      patients who did and did not have ACP discussion. After adjusting for prior
      hospitalization and ED use histories, ACP discussions were associated with a 34%
      less probability of hospitalization (hazard ratios, 0.66; 95% confidence
      interval, 0.45-0.97), and similar effects are apparent on ED use independent of
      age and prior ED use effects. CONCLUSIONS: Patients with chronic diseases
      including mild cognitive impairment can engage in ACP conversations with trusted
      home health care providers. Having ACP conversation is associated with
      significant reduction in seeking urgent health care and in hospitalizations.

PMID- 27875484
TI  - Intraoperative Mania During Deep Brain Stimulation for Parkinson Disease.

PMID- 27875485
TI  - A Comparative Study of the Water Drinking Test in Eyes With Open-Angle Glaucoma
      and Prior Trabeculectomy or Tube Shunt.
AB  - PURPOSE: To compare the intraocular pressure (IOP) response after the water
      drinking test (WDT) in patients who have undergone trabeculectomy or tube shunt
      surgery. METHODS: This prospective study examined 40 eyes of 34 open-angle
      glaucoma subjects who had undergone trabeculectomy (n=20) or tube shunt surgery
      (n=20). Both groups were matched by IOP range and by number of topical
      antiglaucoma medications used. After a baseline IOP assessment, subjects drank 10
      mL water per kg body weight over 15 minutes. IOP was then measured with a Goldman
      tonometer every 15 minutes over a 1-hour period. Outcomes measures were IOP peak,
      fluctuation, mean, and range. RESULTS: No significant differences in baseline
      demographics, baseline clinical characteristics or IOP changes during the WDT
      were observed between the 2 surgical procedure groups. Mean baseline IOPs for the
      tube shunt and trabeculectomy groups were 12.55+/-4.23 and 12.3+/-4.28 mm Hg,
      respectively (P=0.854). In the trabeculectomy and tube shunt groups,
      respectively, peak IOP was 16.25+/-5.55 and 16.15+/-5.36 mm Hg (P=0.954); IOP
      fluctuation (IOP max-IOP baseline) was 3.95+/-2.17 and 3.6+/-2.23 mm Hg
      (P=0.618), and IOP range was 2.78+/-1.56 and 2.8+/-1.47 mm Hg (P=0.959).
      Statistical analysis of IOP fluctuation associations using multivariable linear
      regression determined that the use of systemic antihypertensive blood pressure
      medication was associated with an increase in IOP fluctuation of approximately 2
      mm Hg. CONCLUSIONS: Subjects who had undergone either trabeculectomy or tube
      shunt surgery showed a similar IOP response to the WDT. Subjects on systemic
      antihypertensive medications experienced significantly greater IOP fluctuations
      during the test.

PMID- 27875486
TI  - Evaluation of Corneal Deformation Parameters Provided by the Corvis ST Tonometer
      After Trabeculectomy.
AB  - PURPOSE: The aims of this study were to evaluate how the corneal deformation
      parameters provided by the Corvis ST tonometer (CST) were influenced by pressure
      lowering ocular surgery, and to determine the correlations of intraocular
      pressure (IOP) and axial length (AL) with CST corneal deformation parameters.
      METHODS: This prospective 1-month study enrolled 22 subjects (22 eyes) who
      underwent trabeculectomy combined with mitomycin C. The corneal deformation
      parameters were measured using the CST. IOP was measured before and after surgery
      by a Goldmann applanation tonometer and the CST. The central corneal thickness
      and AL were also recorded. The correlations of the corneal deformation parameters
      with central corneal thickness, AL, and IOP changes were determined by linear
      regression analysis. RESULTS: IOP decreased significantly after surgery. AL was
      significantly shorter at 1 week after surgery. There were significant changes in
      the CST parameters time 1, velocity 1, velocity 2, peak distance highest
      concavity, and deformation amplitude highest concavity at 1 week and 1 month
      after surgery and in time highest concavity at 1 week after surgery. The change
      in time 1 was significantly correlated with preoperative IOP and the IOP
      reductions, and was positively correlated with the decrease in AL at 1 week. The
      increase in velocity 1 was negatively correlated with preoperative IOP, and IOP
      reductions. The change in time highest concavity was negatively correlated with
      IOP before surgery and the decrease in IOP at 1 week. CONCLUSION: CST is a good
      choice for measuring IOP, especially when aiming for normalization of IOP after
      glaucoma surgery.

PMID- 27875487
TI  - Microvascular Compromise Develops Following Nerve Fiber Layer Damage in Normal
      Tension Glaucoma Without Choroidal Vasculature Involvement.
AB  - PURPOSE: To investigate capillary densities in patients with unilateral normal
      tension glaucoma (NTG) and normal controls using optical coherence tomography
      angiography. MATERIALS AND METHODS: We recruited 13 patients with unilateral NTG
      and 13 healthy controls. Optical coherence tomography-angiography was performed
      and pure peripapillary retinal capillary density was calculated after manually
      excluding large vessels and the optic disc. Paired comparison of capillary
      densities was performed among 3 categories of eye: NTG eye, fellow eye, and
      normal eye. Through vascular layer stratification we investigated differences in
      the retinal and choroidal circulation. RESULTS: In total, 33 eyes of 11
      unilateral NTG patients and 11 controls were analyzed. Capillary densities of NTG
      eyes were significantly lower than those of fellow eyes or control eyes (both
      P=0.013). No significant differences were found between fellow eyes and control
      eyes (P=0.328). Area of capillary compromise was identical to the area of retinal
      nerve fiber layer (RNFL) defect in all 11 eyes. In layer analysis, a decrease in
      capillary plexus was demonstrated only in the inner retina and no definite
      changes were found in the outer retina and choroid. Optic nerve head
      microvasculature did not show areas of capillary dropout. CONCLUSIONS: In
      patients with unilateral NTG, we could observe significant retinal capillary
      compromise in the area of RNFL defect. No changes were demonstrated in the
      choroid and optic disc area. We speculated on a possibility of secondary
      microvascular changes in the retina to nerve damage from the wedge-shaped but not
      geographic shaped capillary compromise corresponding to RNFL defect area. Further
      studies on the optic nerve head microvasculature and blood flow are warranted to
      assess their relationship to glaucoma pathogenesis.

PMID- 27875488
TI  - Esomeprazole FDA Approval in Children With GERD: Exposure-Matching and Exposure
      Response.
AB  - OBJECTIVES: Food and Drug Administration approval of proton-pump inhibitors for
      infantile gastroesophageal reflux disease has been limited by intrapatient
      variability in the clinical assessment of gastroesophageal reflux disease. For
      children 1 to 17 years old, extrapolating efficacy from adults for IV
      esomeprazole was accepted. The oral formulation was previously approved in
      children. Exposure-response and exposure matching analyses were sought to
      identify approvable pediatric doses. METHODS: Intragastric pH biomarker
      comparisons between children and adults were conducted. Pediatric doses were
      selected to match exposures in adults and were based on population
      pharmacokinetic (PK) modeling and simulations with pediatric esomeprazole data.
      Observed IV or oral esomeprazole PK data were available from 50 and 117 children,
      between birth and 17 years, respectively, and from 65 adults, between 20 and 48
      years. A population PK model developed using these data was used to simulate
      steady-state esomeprazole exposures for children at different doses to match the
      observed exposures in adults. RESULTS: Exposure-response relationships of
      intragastric pH measures were similar between children and adults. The PK
      simulations identified a dosing regimen for children that results in comparable
      steady-state area under the curve to that observed after 20 mg in adults. For IV
      esomeprazole, increasing the infusion duration to 10 to 30 minutes in children
      achieves matching Cmax values with adults. CONCLUSIONS: The exposure-matching
      analysis permitted approval of an esomeprazole regimen not studied directly in
      clinical trials. Exposure-response for intragastric pH-permitted approval for the
      treatment of gastroesophageal reflux disease in children in whom it was not
      possible to evaluate the adult primary endpoint, mucosal healing assessed by
      endoscopy.

PMID- 27875489
TI  - Femoral Medialization, Fixation Failures, and Functional Outcome in Trochanteric
      Hip Fractures Treated With Either a Sliding Hip Screw or an Intramedullary Nail
      From Within a Randomized Trial.
AB  - OBJECTIVES: The aim of this study was to determine if femoral medialization
      influences residual pain and mobility and to determine if fixation method or
      fracture pattern influences the tendency to medialize. DESIGN: This study used
      data from within a randomized controlled trial. SETTING: Peterborough City
      Hospital, UK. PATIENT/PARTICIPANTS: Eight hundred forty-four patients presenting
      with a trochanteric hip fracture were randomized. Five hundred thirty-eight were
      available for 1-year follow-up. Fractures were classified according to OTA/AO
      classification as 31 A1, A2, and A3. INTERVENTION: Randomized to fixation with a
      Targon proximal femoral nail or sliding hip screw (SHS). OUTCOME MEASURES:
      Femoral medialization was calculated from follow-up x-rays at a minimum of 28
      days post-fixation. Pain and mobility scores were assessed at 1 year by an
      independent blinded observer. Fixation failure and revision procedures were
      assessed at a minimum of 1 year from injury. RESULTS: Patients with >50%
      medialization had worse pain (P = 0.012) and mobility scores (P = 0.013) at 1
      year. They also had more fracture healing complications (P = 0.021) and required
      more revision procedures (P = 0.014). Fractures treated with SHS were more likely
      to medialize >50% compared with intramedullary nail (P < 0.001). A2 and A3
      fractures were more likely to medialize, and A3 fractures were more likely to
      undergo >50% medialization (P < 0.001). CONCLUSIONS: Our study demonstrates the
      previously theoretical predisposition for unstable hip fractures treated with SHS
      to undergo femoral medialization and correlates this with worse functional
      outcomes. It supports the use of intramedullary nails for A3 fractures, which
      have a significant tendency to medialize. LEVEL OF EVIDENCE: Prognostic level II.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 27875490
TI  - Impact of an Integrated Hip Fracture Inpatient Program on Length of Stay and
      Costs.
AB  - BACKGROUND: Hip fractures are associated with significant morbidity and
      mortality. Co-management models pairing orthopaedic surgeons with hospitalists or
      geriatricians may be effective at improving processes of care and outcomes such
      as length of stay (LOS) and cost. We set out to determine the effect of an
      integrated hip fracture co-management model on LOS, cost, and process measures.
      METHODS: We conducted a single-center pre-post study of 571 patients admitted to
      an academic medical center with hip fractures between January 2009 and December
      2013. The group receiving an integrated medical-surgical co-management
      incorporating continuous improvement methodology was compared with a control
      population. Primary outcome was LOS. Secondary outcomes included cost per case,
      time to surgery, osteoporosis (OP) treatment, preoperative echocardiogram
      utilization, mortality, and readmission. RESULTS: LOS decreased from 18.2 (1.1)
      to 11.9 (1.5) days, a reduction of 6.3 days (P < 0.001). Mean cost decreased by
      $4953 (P < 0.001) per case. Mean time to surgery decreased from 45.8 (66.8) to
      29.7 (17.9) hours (P < 0.001). Initiation of OP treatment increased from 55.8% to
      96.4% (P < 0.001). Preoperative echocardiogram use decreased from 15.8% to 9.1%
      (P < 0.05). There was a nonsignificant difference in mortality rate (5.0% vs.
      2.1%, P = 0.06). Readmission rate remained unchanged (4.6% vs. 6.0%, P = 0.56).
      CONCLUSIONS: An integrated medical-surgical co-management model incorporating
      continuous improvement methodology was associated with reduced LOS, costs, time
      to surgery, and increased initiation of appropriate OP treatment. LEVEL OF
      EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 27875492
TI  - Invited Commentary Related to: "Assessing the Efficacy of Prothrombin Complex
      Concentrate in Multiply Injured Patients With High-Energy Pelvic and Extremity
      Fractures".

PMID- 27875491
TI  - Assessing the Efficacy of Prothrombin Complex Concentrate in Multiply Injured
      Patients With High-Energy Pelvic and Extremity Fractures.
AB  - OBJECTIVES: Prothrombin complex concentrate (PCC) is being increasingly used for
      reversing induced coagulopathy of trauma. However, the use of PCC for reversing
      coagulopathy in multiply injured patients with pelvic and/or lower extremity
      fractures remains unclear. The aim of our study was to assess the efficacy of PCC
      for reversing coagulopathy in this group of patients. DESIGN: Two-year
      retrospective analysis. SETTING: Our level I trauma center.
      PATIENTS/PARTICIPANTS: All coagulopathic [International normalized ratio (INR)
      >=1.5] trauma patients. Patients with femur, tibia, or pelvic fracture were
      included. Patients were divided into 2 groups: PCC (single dose) and fresh frozen
      plasma (FFP). Patients in the 2 groups were matched using propensity score
      matching. MAIN OUTCOME MEASUREMENTS: Time to correction of INR, time to
      intervention, development of thromboembolic complications, mortality, and cost of
      therapy. RESULTS: A total of 81 patients (PCC: 27, FFP: 54) were included.
      Patients who received PCC had faster correction of INR and shorter time to
      surgical intervention in comparison to patients who received FFP. PCC therapy was
      also associated with lower overall blood product requirement (P = 0.02) and lower
      transfusion costs (P = 0.0001). CONCLUSIONS: In a matched cohort of multiply
      injured patients with pelvic and/or lower extremity fractures, administration of
      a single dose of PCC significantly reduced the time to correction of INR and time
      to intervention compared with patients who received FFP therapy. This may allow
      orthopaedic surgeons to more safely proceed with early, definitive fixation
      strategies. LEVEL OF EVIDENCE: Therapeutic level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 27875493
TI  - Acute Lumbar Paraspinal Myonecrosis in Football Players with Sickle Cell Trait: A
      Case Series.
AB  - We report six cases of a novel syndrome of acute, exertional low back pain in
      football players, five in college and one in the National Football League. All
      six are African Americans with sickle cell trait (SCT). The acute low back pain
      is severe and can be disabling, and the condition can be confused with muscle
      strain, discogenic pain, stress fracture, or other problems in athletes. Our
      evidence shows that this syndrome is caused by lumbar paraspinal myonecrosis
      (LPSMN), which likely often contributes to the lumbar paraspinal compartment
      syndrome. We explain why we believe SCT is a risk factor for LPSMN in football
      conditioning/training, although SCT is not requisite for this syndrome, which has
      been reported rarely in other sports (e.g., snow or water skiing) and especially
      in weight lifting that targets lumbar muscles. The clinical course of LPSMN in
      football can be mild and allow return to play in a week or two, or it can be
      severe and lead to long-term sequelae. Knowledge of this syndrome will enable
      athletic trainers and team physicians to diagnose it early, treat it properly,
      and lessen its effect. Further research will help us learn how better to prevent
      it.

PMID- 27875494
TI  - Verification of Maximal Oxygen Uptake in Obese and Nonobese Children.
AB  - PURPOSE: The purpose of this study was to examine whether a supramaximal constant
      load verification test at 105% of the highest work rate would yield a higher
      VO2max when compared with an incremental test in 10- to 12-yr-old nonobese and
      obese children. METHODS: Nine nonobese (body mass index percentile = 57.5 +/-
      23.2) and nine obese (body mass index percentile = 97.9 +/- 1.4) children
      completed a two-test protocol that included an incremental test followed 15 min
      later by a supramaximal constant-load verification test. RESULTS: The VO2max
      achieved in verification testing (nonobese = 1.71 +/- 0.31 L.min and obese = 1.94
      +/- 0.47 L.min) was significantly higher than that achieved during the
      incremental test (nonobese = 1.57 +/- 0.27 L.min and obese = 1.84 +/- 0.48 L.min;
      P < 0.001). There was no significant group (i.e., nonobese vs obese)-test (i.e.,
      incremental vs verification) interaction, suggesting that there was no effect of
      obesity on the difference between verification and incremental VO2max (P =
      0.747). CONCLUSION: A verification test yielded significantly higher values of
      VO2max when compared with the incremental test in obese children. Similar results
      were observed in nonobese children. Supramaximal constant-load verification is a
      time-efficient and well-tolerated method for identifying the highest VO2 in
      nonobese and obese children.

PMID- 27875496
TI  - Exercise Attenuates High-Fat Diet-induced Disease Progression in 3xTg-AD Mice.
AB  - PURPOSE: Little is known regarding the therapeutic role of exercise against the
      risk of a high-fat diet (HFD) for Alzheimer's disease (AD) and AD-like cognitive
      deficits. This study aimed to investigate the therapeutic effect of treadmill
      running against HFD-induced progression in AD neuropathology and cognitive
      impairments in the triple-transgenic AD (3xTg-AD) mice. METHODS: The 3xTg-AD mice
      were assigned to a chow diet (control, n = 10), an HFD (n = 10), or an HFD
      combined with exercise (HFD + EX, n = 10) group. Mice in the HFD were fed with a
      60% fat diet for 20 wk. The HFD + EX mice were additionally subjected to
      treadmill running. RESULTS: Compared with the control mice, the HFD mice had
      impaired brain insulin signaling, exacerbated AD neuropathology, defects in
      synaptic stability/plasticity, and apoptotic neuronal cell death in conjunction
      with exacerbated cognitive deficits in the affected brain regions, which were all
      significantly alleviated in the HFD + EX mice. CONCLUSION: The current findings
      suggest that treadmill running protects against AD-like disease progression and
      cognitive deficits caused by an HFD in the 3xTg-AD mice.

PMID- 27875497
TI  - Physical Activity: Absolute Intensity versus Relative-to-Fitness-Level Volumes.
AB  - PURPOSE: This study aimed to investigate in a real-life setting how moderate- and
      vigorous-intensity physical activity (PA) volumes differ according to absolute
      intensity recommendation and relative to individual fitness level by sex, age,
      and body mass index. METHODS: A total of 23,224 Finnish employees (10,201 men and
      13,023 women; ages 18-65 yr; body mass index = 18.5-40.0 kg.m) participated in
      heart rate recording for 2+ d. We used heart rate and its variability,
      respiration rate, and on/off response information from R-R interval data
      calibrated by participant characteristics to objectively determine daily PA
      volume, as follows: daily minutes of absolute moderate (3-<6 METs) and vigorous
      (>=6 METs) PA and minutes relative to individual aerobic fitness for moderate
      (40%-<60% of oxygen uptake reserve) and vigorous (>=60%) PA. RESULTS: According
      to absolute intensity categorization, the volume of both moderate- and vigorous
      intensity PA was higher in men compared with women (P < 0.001), in younger
      compared with older participants (P < 0.001), and in normal weight compared with
      overweight or obese participants (P < 0.001). When the volume of PA intensity was
      estimated relative to individual fitness level, the differences were much
      smaller. Mean daily minutes of absolute vigorous-intensity PA were higher than
      those of relative intensity minutes in normal weight men ages 18-40 yr (17.7, 95%
      confidence interval [CI] = 16.9-18.6, vs 8.6, 95% CI = 8.0-9.1; P < 0.001), but
      the reverse was the case for obese women ages 41-65 yr (0.3, 95% CI = 0.2-0.4, vs
      7.8, 95% CI = 7.2-8.4; P < 0.001). CONCLUSION: Compared with low-fit persons,
      high-fit persons more frequently reach an absolute target PA intensity, but
      reaching the target is more similar for relative intensity.

PMID- 27875498
TI  - A Murine Model of Robotic Training to Evaluate Skeletal Muscle Recovery after
      Injury.
AB  - PURPOSE: In vivo studies have suggested that motor exercise can improve muscle
      regeneration after injury. Nevertheless, preclinical investigations still lack
      reliable tools to monitor motor performance over time and to deliver optimal
      training protocols to maximize force recovery. Here, we evaluated the utility of
      a murine robotic platform (i) to detect early impairment and longitudinal
      recovery after acute skeletal muscle injury and (ii) to administer varying
      intensity training protocols to enhance forelimb motor performance. METHODS: A
      custom-designed robotic platform was used to train mice to perform a forelimb
      retraction task. After an acute injury to bilateral biceps brachii muscles,
      animals performed a daily training protocol in the platform at high (HL) or low
      (LL) loading levels over the course of 3 wk. Control animals were not trained
      (NT). Motor performance was assessed by quantifying force, time, submovement
      count, and number of movement attempts to accomplish the task. Myofiber number
      and cross-sectional area at the injury site were quantified histologically.
      RESULTS: Two days after injury, significant differences in the time, submovement
      count, number of movement attempts, and exerted force were observed in all mice,
      as compared with baseline values. Interestingly, the recovery time of muscle
      force production differed significantly between intervention groups, with HL
      group showing a significantly accelerated recovery. Three weeks after injury, all
      groups showed motor performance comparable with baseline values. Accordingly,
      there were no differences in the number of myofibers or average cross-sectional
      area among groups after 3 wk. CONCLUSION: Our findings demonstrate the utility of
      our custom-designed robotic device for the quantitative assessment of skeletal
      muscle function in preclinical murine studies. Moreover, we demonstrate that this
      device may be used to apply varying levels of resistance longitudinally as a
      means manipulate physiological muscle responses.

PMID- 27875499
TI  - Impact of Acute Dietary Manipulations on DXA and BIA Body Composition Estimates.
AB  - PURPOSE: To examine the effects of acute preassessment diets on body composition
      estimates obtained by dual-energy x-ray absorptiometry (DXA) and bioelectrical
      impedance analysis (BIA). METHODS: In a counterbalanced design, 48 males and
      females were provided with two 1-d diets: high-carbohydrate diet (9 g CHO.kg) and
      very low-carbohydrate diet (1 to 1.5 g CHO.kg). For each condition, body
      composition was assessed in the morning after an overnight fast, in the afternoon
      after feeding, and the following morning after a second overnight fast. RESULTS:
      Acute food ingestion, regardless of macronutrient content, altered DXA and BIA
      body composition estimates, and both sexes responded similarly. DXA total and
      regional lean soft tissue estimates increased up to 1.7% and 3% on average in
      response to feeding, with individual increases of over 4.5% and 9%. DXA total and
      trunk fat mass estimates decreased by up to 3% on average. All DXA-derived
      measures of body composition returned to baseline values after the second
      overnight fast. Impedance measured by BIA decreased by 4.4% in response to
      feeding, leading to a 2% increase in total body water and fat-free mass, with
      individual increases up to 4.5%. BIA fat mass estimates decreased 1.4% to 2.4%,
      with individual decreases of up to 10%. Unlike DXA, most BIA-derived estimates
      did not return to baseline values after a second overnight fast. CONCLUSIONS:
      Acute food and fluid intake can artificially influence body composition
      estimates, regardless of macronutrient content. An overnight fast is likely
      sufficient preassessment dietary control for DXA and possibly sufficient for BIA.

PMID- 27875500
TI  - Activity Levels for Four Years in a Cohort of Urban-Dwelling Adolescent Females.
AB  - PURPOSE: Evidence suggests that female adolescents and those living in urban
      environments may have lower physical activity (PA) levels compared with their
      peers. Yet few studies report PA for urban adolescent females, and there is no
      consensus regarding potential causes for low PA in this subgroup. We examined PA
      levels, in a large, diverse cohort of 14- to 17-yr-old urban-dwelling females and
      assessed the effect of socioeconomic, personal, and neighborhood/environmental
      factors on PA. METHODS: One week of time-stamped step count data were collected
      on 926 girls from the Pittsburgh Girls Study at four annual visits. Valid
      recordings (worn at least 10 h on 3+ d) were examined and compared with
      normalized step count values from a U.S. population-representative sample.
      Relationships between important covariates and average steps per day were
      examined with regression models. RESULTS: Adjusted mean +/- SD step counts per
      day at baseline were 5614 +/- 2434 after controlling for important covariates
      with less than 6% of girls achieving at least 10,000 steps per day. The girls
      from the Pittsburgh Girls Study accrued ~45% of their steps during school hours.
      Age-specific median step counts per day for study participants were similar to
      the 25th percentile of U.S. population normalized values and did not
      significantly change during follow-up. Non-Hispanic African American
      race/ethnicity was associated with higher average step counts per day; obesity
      and a recent childbirth were associated with lower average step counts per day.
      CONCLUSIONS: Step counts in this cohort of urban adolescent girls were
      considerably lower than expected for U.S. adolescent females. Targeted efforts to
      improve PA levels in urban youth should consider the importance of school-based
      activity while increasing PA opportunities outside of school.

PMID- 27875501
TI  - Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized
      Controlled Trial in Older Women.
AB  - INTRODUCTION/PURPOSE: Resistance training with ibuprofen supplementation may
      improve musculoskeletal health in postmenopausal women. The study purpose was to
      determine the efficacy of resistance training and ibuprofen supplementation on
      bone and muscle properties in postmenopausal women. METHODS: Participants (n =
      90, 65.3 +/- 4.9 yr) were randomly assigned to: supervised resistance training or
      stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo
      supplementation for 3 d.wk (9 months). Baseline and postintervention measurements
      included distal and shaft scans of the forearm and lower leg using peripheral
      quantitative computed tomography. Distal site outcomes included cross-sectional
      area, content, and density for total and trabecular bone, as well as estimated
      bone strength in compression. Shaft site outcomes included total bone area;
      cortical bone area, content, and density; estimated bone strength in torsion; and
      muscle area and density. RESULTS: Exercise-supplement-time interactions for total
      bone content at the distal radius (P = 0.009) and cortical density at the radius
      shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased
      total bone content (-1.5%) at the distal radius in comparison to the resistance
      training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in
      cortical density at the radius shaft differed between the stretching with placebo
      and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance
      training preserved muscle density in the lower leg more so than stretching (-3.1%
      vs -5.4%; P = 0.015). CONCLUSIONS: Ibuprofen consumed immediately after
      resistance training had a deleterious effect on bone mineral content at the
      distal radius, whereas resistance training or ibuprofen supplementation
      individually prevented bone loss. Resistance training prevented muscle density
      decline in the lower leg.

PMID- 27875502
TI  - Sniffing Out Paediatric Gastrointestinal Diseases: The Potential of Volatile
      Organic Compounds as Biomarkers for Disease.
AB  - The diagnostic work-up and follow-up of paediatric functional gastrointestinal
      disorders and organic conditions usually includes invasive tests, carrying a high
      burden on patients. There is a place, therefore, for novel, noninvasive disease
      specific biomarkers. Volatile organic compounds (VOCs), originating from
      (patho)physiological metabolic processes in the human body, are excreted as waste
      products through all conceivable bodily excrements. The spectrum of VOCs harbours
      a magnificent source of information, with the potential to serve as noninvasive
      diagnostic biomarkers and to monitor disease activity. VOC analysis has been
      studied in children and infants with a variety of gastrointestinal diseases,
      including inflammatory bowel disease, liver diseases, irritable bowel syndrome,
      necrotizing enterocolitis and infectious diarrhoea. Most of these studies,
      although limited in sample size, show that patients can be discriminated from
      controls based on their VOC profiles, underscoring the potential of VOC analysis
      in diagnosis and follow-up. Currently, however, the application of VOC analysis
      in clinical practice is limited; substantial challenges, including
      methodological, biological, and analytical problems, still need to be met. In
      this review we provide an overview of the available literature on the potential
      of VOCs as biomarkers for paediatric gastrointestinal diseases. We discuss the
      available techniques to analyse VOCs and provide topics for VOC-related research,
      which need to be addressed before VOC diagnostics can be implemented in daily
      clinical practice.

PMID- 27875503
TI  - Influence of Partial External Biliary Diversion on the Lipid Profile in Children
      With Progressive Familial Intrahepatic Cholestasis.
AB  - OBJECTIVES: The concentration of bile acids is highly increased in progressive
      familial intrahepatic cholestasis (PFIC). Bile acids are the end products of
      cholesterol metabolism, and aid in the absorption of fat-soluble vitamins and
      dietary fat. The aim of our study was to investigate lipid metabolism in patients
      with PFIC with focus on the effect of partial external biliary diversion (PEBD).
      METHODS: In 26 patients with PFIC, who underwent PEBD surgery at the median age
      of 2.2 years (range: 0.4-16.6), we analyzed the concentrations of lipids and
      apolipoproteins both before and 6 months after PEBD. Patients were split into 2
      groups according to the outcome of surgery (either "good" or "poor"), and were
      analyzed separately. A "good" result following surgery was defined as complete
      relief from pruritus, and normalization of total bilirubin (<1.0 mg/dL) and bile
      acid concentration in serum (<12 MUmol/L). RESULTS: We found abnormal lipid
      concentrations at baseline in all 26 patients: cholesterol was increased (>190
      mg/dL) in 13 patients, phospholipids were increased (>250 mg/dL) in 5 patients,
      and triglyceride concentration was increased (>150 mg/dL) in 13 patients. After
      PEBD, the concentrations of plasma cholesterol, triglycerides, and phospholipids
      decreased significantly, whereas, ApoA-I and high-density lipoprotein cholesterol
      concentrations increased and the concentrations of apolipoprotein B, low-density
      lipoprotein cholesterol, and very low-density lipoprotein cholesterol
      significantly decreased. PEBD had neither an effect on ApoE concentration nor on
      lecithin-cholesterol acyl transferase activity. In the group with a "poor"
      outcome report following PEBD, total serum cholesterol concentration decreased
      significantly, and no effect on the concentrations of triglycerides and
      phospholipids were observed. CONCLUSIONS: Patients with PFIC present with a high
      risk of lipid disturbances. PEBD has a beneficial effect on lipid profile in the
      majority of cases.

PMID- 27875504
TI  - Screening for Psychosocial and Family Risk in Pediatric Gastrointestinal
      Disorders.
AB  - OBJECTIVES: Screening for psychosocial comorbidity is recommended for pediatric
      patients presenting at an initial gastroenterology (GI) outpatient consultation.
      We developed and evaluated the psychometric properties of the GI Screener to
      address the need for a screening tool specific to pediatric GI patients. METHODS:
      128 patients (8-18 years old, 63% female) and 126 parents completed age-specific
      versions of the GI Screener and 3 validated psychosocial comparison instruments
      (The Behavioral Assessment System for Children, The Functional Disability
      Inventory, The General Functioning scale of the Family Assessment Device) at
      their initial GI consultation. (30%) of families repeated the measures 2 weeks
      later. We identified GI Screener content domains and retained items using
      exploratory factor analysis. We evaluated internal consistency, construct
      validity, cross-informant reliability, and test-retest reliability of the trimmed
      measures. RESULTS: Exploratory factor analysis identified 2 factors in both the
      parent and child scales: Symptom Impact and Emotional Functioning. Internal
      consistency estimates for the trimmed scales were good (Cronbach's alpha >0.75)
      for both Child and Parent scales. We found that the GI Screener for both patient
      and parents had good construct validity. Cross-informant reliability between
      Parent and Child scales at baseline had an estimated correlation of 0.56, while
      intra class correlation coefficients between baseline and 2-week scores showed
      high test-retest reliability (>0.7). CONCLUSIONS: The GI Screener is a brief,
      valid and reliable measure that can aid in identifying families who are at high
      risk for psychosocial comorbidity facilitating the targeted delivery of
      psychosocial intervention and efficient use of health care resources.

PMID- 27875506
TI  - Nerve Combing for Trigeminal Neuralgia Without Vascular Compression.
AB  - OBJECTIVE: The aim of this study was to describe and evaluate the long-term
      clinical outcome of "nerve combing" for trigeminal neuralgia (TN) without
      vascular compression. METHODS: Fifteen patients with TN treated with
      microvascular decompression had no visible vascular compression intraoperatively.
      All of them underwent trigeminal nerve combing. RESULTS: The long-term excellent
      relief was achieved in 73.3% of patients, 2 patients had good outcome, 1 patient
      experienced obvious partial relief, and the intensity of the residual pain was
      not severe enough to require medication. Three patients suffered facial numbness
      postoperatively, but it completely disappeared by 4 months after operation.
      CONCLUSION: Nerve combing is an effective method in treating TN without vascular
      compression; however, further studies should be carried out to explore the
      possible mechanisms of underlying pain relief.

PMID- 27875505
TI  - Radiologic Predictors of Surgery in Newly Diagnosed Pediatric Crohn Disease
      Patients.
AB  - OBJECTIVES: The aim of the present study was to assess whether small bowel
      imaging conducted at the time of diagnosis could be used as a predictor of small
      bowel surgical intervention in a population of pediatric patients with Crohn
      disease (CD). METHODS: A retrospective analysis of small bowel imaging within 30
      days of diagnosis of pediatric CD was conducted. Patients were divided into 2
      groups based on small bowel imaging: those with no or minor abnormalities (71%)
      and those with more extensive or obstructive abnormalities (29%). Medical records
      were reviewed for small bowel surgical intervention and clinic follow-up visits.
      RESULTS: A total of 232 patients were included in the study group (average age at
      diagnosis 11.7 years). Twenty-seven patients (12%) underwent small bowel surgical
      intervention. The relative risk for small bowel surgical intervention was 2.91 in
      the group with more extensive imaging abnormalities. The majority of increased
      surgical risk occurred in the first year after diagnosis, when the normal-minor
      group had a 2% surgical risk and the more abnormal group had a 17% surgical risk.
      Both groups had a 2% to 3% surgical risk per year after the first year.
      CONCLUSIONS: Small bowel imaging at the time of diagnosis in pediatric CD can
      help predict the risk of small bowel surgical intervention and should be
      recommended for all newly diagnosed patients. Nearly one third of our cohort
      underwent small bowel surgical intervention through 8 years of follow-up.
      Surgical complications of CD often occur in the small bowel, and counseling
      families about surgical risk is an integral part of pediatric CD management.

PMID- 27875507
TI  - Technical Variants of Mandibular Median Distraction.
AB  - Distraction of the mandibular symphysis, initially described by Guerrero, is
      often indicated in instances of osseous deficiency in the anterior mandible with
      associated tooth-jaw discrepancy. The authors describe a technique, combined with
      orthodontic treatment, which offers a safe and reliable alternative to avulsions
      and coronoplasty. Three operative techniques are outlined in detail.

PMID- 27875508
TI  - Extensive Oral Mucormycosis in a Transplanted Patient.
AB  - Mucormycosis is an invasive fungal disease caused by fungi from the Mucorales
      order that are found in the soil and decaying organic debris. Mucormycosis has
      been reported to be the third most common fungal disease in stem cell
      transplanted patients. The fungi have a tendency for vascular invasion, resulting
      in thrombi development, which decreases blood supply and leads to extensive
      tissue necrosis. Here, the authors present a patient of mucormycosis affecting
      the soft palate, oropharynx, and hypopharynx in a type II diabetic male patient
      who underwent allogeneic stem cell transplantation, and the authors further
      review the literature on oral mucormycosis for the last 10 years.

PMID- 27875510
TI  - Facial Evaluation in Holoprosencephaly.
AB  - Holoprosencephaly (HPE) is a malformation of the brain, occurring during the
      first weeks of pregnancy, that may be associated with several craniofacial
      alterations and different pathological conditions.The authors describe a 2-year
      old girl with lobar HPE, epilepsy, but with a roughly normal face. Despite the
      macroscopic, clinical appearance, a facial morphometric analysis, performed
      through a stereophotogrammetric system, showed features that diverge from
      reference subjects and that are considered typical of HPE.This study highlights
      how a digital anthropometric facial assessment through stereophotogrammetry can
      be a useful and noninvasive instrument to investigate the facial features of HPE,
      especially in the presence of an apparently normal facial aspect. Additionally,
      it can provide the bases for future insights about the relationship between
      embryological facial and cerebral development, the time of the occurred defect
      and, in the end, enrich basic scientific knowledge.

PMID- 27875509
TI  - Osseous Repair in Minimally Invasive Reconstruction of Anterior Skull Base
      Defects.
AB  - Management of anterior skull base defects is an area of continued innovation for
      skull base surgeons. Various grafting materials have been advocated for the
      repair of skull base defects depending on needs, availability, harvest site
      morbidity, and surgeon preference. Spontaneous bony closure of small skull
      defects is known to occur in animal models without bone grafts, but this
      phenomenon has been unexplored in the human skull base. The objective of this
      study was to evaluate osseous skull base closure in patients undergoing
      endoscopic repair of skull base defects. A retrospective review was performed on
      13 patients who underwent endoscopic repair of skull base defects with free bone
      grafts who were followed with postoperative computed tomography scans. This
      cohort was compared to postoperative radiology from patients undergoing
      transsphenoidal surgery without rigid reconstruction to evaluate for spontaneous
      osseous closure of sellar defects. Free bone grafts are incorporated into the
      bony skull base in the majority of patients (84.6% with at least partial
      incorporation) at mean of 5.3 years postoperatively. By comparison, patients
      undergoing pituitary surgery did not demonstrate spontaneous osseous closure on
      postoperative imaging. Human anterior skull base defects do not appear to
      spontaneously close, even when small, suggesting that there is no "critical size
      defect" in the human skull base, in contrast to the robust wound healing in
      animal models of skull convexity and mandibular defects. Free bone grafts
      incorporate into the skull base over the long-term and may be utilized whenever a
      rigid skull base reconstruction is desired, regardless of the defect size.

PMID- 27875511
TI  - Survival of Nasal Tip Flap on Only the Columellar Attachment.
AB  - The nose has a robust blood supply derived from both internal and external
      carotid arteries. The main blood supply of the nasal tip and skin is derived
      primarily from the lateral nasal arteries, with a variable contribution from the
      columellar arteries. We present a patient with cut nose resulting from a
      homicidal attack in which the lower two-thirds of the nose was severed starting
      at the bony-cartilaginous junction of the dorsum of the nose down to the tip of
      the nose. The skin-cartilage flap was attached only to the columella and to the
      caudalmost 3 mm of the left ala nasi. The detached skin-cartilage flap was
      replaced and sutured anatomically, and the flap completely survived in spite of
      cutting of both lateral and dorsal nasal arteries.

PMID- 27875512
TI  - Single-Tooth Osteotomy Combined Wide Linear Corticotomy Under Local Anesthesia
      for Correcting Anterior Protrusion With Ectopically Erupted Canine.
AB  - BACKGROUNDS: This article presents the alternative surgical treatments of both
      anterior protrusion by carrying out retraction on mandibular anterior fragment,
      meanwhile applying retraction force on maxilla anterior teeth and ectopically
      erupted canine with using platelet-rich fibrin (PRF). METHODS: Anterior segmental
      osteotomy was combined with linear corticotomy under local anesthesia. The
      correction of right ectopic canine was achieved through 2 stages. First, dento
      osseous osteotomy on palatal side was performed. Then second osteotomy with
      immediate manual repositioning of the canine with concomitant first premolar
      extraction was enhanced with PRF, which was prepared by centrifuging patient's
      blood, applied into buccal side of high canine during osteotomy. Mandibular
      retraction was accomplished by anterior segmental osteotomy. RESULTS: Single
      tooth osteotomy is a more effective surgical method for ankylosed or ectopically
      erupted tooth in orthodontic treatment. It can reduce the total orthodontic
      treatment time and root resorption, 1 common complication. Significant improved
      bone formation was seen with the addition of PRF on noncritical size defects in
      the animal model. It is reasonable to think that PRF can promote bone
      regeneration. So early bone formation also can reduce the complication such as
      postoperative infection. CONCLUSIONS: As an alternative to anterior protrusion
      and ectopically erupted canine treatment, segmental osteotomy and corticotomy
      combined platelet-rich plasma can enhance orthodontic treatment outcome.

PMID- 27875513
TI  - Post-Traumatic Trigeminal Neuropathy Caused by an Orbital Stab Wound.
AB  - Sensory and motor neuropathy of the trigeminal nerve due to trauma is quite rare.
      Furthermore, there have been no detailed reports on occlusal abnormalities and
      trismus associated with post-traumatic trigeminal motor neuropathy. Here, the
      authors report a case of trigeminal motor neuropathy and trigeminal sensory
      neuropathy in all 3 divisions caused by an orbital stab wound. During kendo
      practice, a 61-year-old man was injured in his right medial canthus with the
      splinter of a broken bamboo sword. Imaging examinations did not show a brain
      injury or orbital bone fracture. Intraoral and extraoral examination and needle
      electromyography revealed trismus, posterior open bite, and denervation of the
      right masseter. After the injury, the patient strived to use the right molars
      during mastication and began chewing exercises in the right molar region. A
      follow-up examination 7 months after the injury revealed an improvement of the
      functional problems in the masticatory system. Although slight facial numbness in
      the right ophthalmic division remained, the patient was satisfied with the
      present status. Further knowledge concerning the natural history of trigeminal
      neuropathy as well as the treatment of choice should be explored in the future.

PMID- 27875514
TI  - Domino Flaps for Repairing of Secondary Bilateral Cleft Lip With Severe Columella
      Deformity.
AB  - The patients with secondary bilateral cleft lip and nasal deformity always suffer
      from a serious part of the horizontal and vertical soft tissue deficiencies in
      the upper lip and nose, especially the columella. Normally, the Abbe flap is used
      to increase the soft tissue volume of upper lip. However, how to reconstruct the
      sever columella deficient, how to make full use of the Abbe flap and the
      remaining soft tissue of the upper lip, are always the problems that need to be
      solved by plastic surgeons. Twenty-nine patients with secondary bilateral cleft
      lip and severe columella deficiency were simultaneously reconstructed with
      several local flaps like dominos that was called "Domino sliding flaps." Six of
      the patients had their nasal tip and dorsum or collumella augmented and modified
      with autologous costal cartilage at the same time. The other 23 patients
      underwent the autologous auricular cartilage augmentation. The patients were
      followed from 15 months to 50 months. No secondary deformation occurred in any of
      the patients. 93.1% patients were satisfied with the aesthetics postoperatively,
      89.7% patients were satisfied with the incision and donor site scar. Among them,
      3 of the patients got hypertrophic scar on the upper lip and were modified 1 year
      after their first operations. The operational technique of the domino sliding
      flaps could better play the role of the Abbe flap. It also gave plastic surgeons
      an effective method to modify the severe deformities of bilateral cleft lip in 1
      stage.

PMID- 27875515
TI  - Reconstruction of Congenital Mandibular Hypoplasia With Microvascular Free Fibula
      Flaps in the Pediatric Population: A Paradigm Shift.
AB  - BACKGROUND: The microvascular free fibula flap has become the gold standard for
      reconstruction of complex mandibular defects since its description by Hidalgo in
      1989. Prior studies have demonstrated its safety and efficacy in the pediatric
      population. However, this reconstructive method is often used only as a last
      resort for correction of congenital mandibular hypoplasia, after failure of bone
      grafting and distraction osteogenesis. The authors describe our experience using
      this technique, facilitated by virtual planning and prefabricated cutting jigs,
      for children with severe congenital mandibular hypoplasia. METHODS: All patients
      with mandibular reconstruction with a fibula flap in children with congenital
      mandibular hypoplasia between 2009 and 2014 by the senior authors were
      identified. Each patient underwent preoperative computed tomography scanning and
      virtual surgical planning to create custom cutting jigs for creation of the
      mandibular defect and fibular osteotomies. Preoperative, intraoperative, and
      postoperative medical records were examined in detail. RESULTS: Five patients age
      10 to 18 with congenital mandibular hypoplasia and Pruzansky Grade III mandibles
      underwent microvascular free fibula flap for mandibular reconstruction during
      this period. Flap success rate was 100%. All patients underwent subsequent
      revision procedures to improve symmetry or for hardware removal. The 4 patients
      in our series who required dental implants were able to have them placed into
      their mandibular reconstruction. CONCLUSIONS: Preoperative virtual planning and
      prefabricated cutting jigs allow for precise complex fibula reconstruction of the
      mandible in the pediatric population. Additionally, virtual planning facilitates
      concomitant orthognathic procedures in patients with hemifacial microsomia. Our
      early success in this patient population leads us to suggest that while the free
      fibula can be safely and successfully used after multiple prior surgical
      interventions in the same anatomic region, it can also be a powerful tool for
      primary correction of congenital mandibular hypoplasia.

PMID- 27875516
TI  - Trastuzumab-associated cardiac events in the Persephone trial.
AB  - BACKGROUND: We report cardiac events in the Persephone trial which compares 6-12
      months of adjuvant trastuzumab in women with confirmed HER2-positive, early-stage
      breast cancer. METHODS: Clinical cardiac events were defined as any of the
      following: symptoms and/or signs of congestive heart failure (CHF) and new or
      altered CHF medication. In addition, left ventricular ejection fraction (LVEF)
      was measured at baseline and then 3 monthly for 12 months. RESULTS: A total of
      2500 patients, aged 22-82, were included: 1251 randomised to 12 months and 1249
      to 6 months of trastuzumab treatment. A total of 93% (2335/2500) received
      anthracyclines, 49% of these (1136/2335) with taxanes. Cardiotoxicity delayed
      treatment in 6% of 12-month and 4% of 6-month patients (P=0.01), and stopped
      treatment early in 8% (96/1214) of 12-month and 4% (45/1216) of 6-month patients
      (P<0.0001). Between 7 and 12 months, more 12-month than 6-month patients had
      LVEFs<50% (8% vs 5%; P=0.004). LVEFs showed quadratic change over time, and 6
      month patients had a more rapid recovery (P=0.02). In a landmark analysis twice
      as many 12-month patients, free of cardiac events at 6 months, had cardiac
      problems in months 7-12 (6% (66/1046) vs 3% (29/1035) of 6-month patients
      (P=0.0002)). Lower baseline LVEF predicted more cardiac dysfunction in both arms
      (reference ?65%: 55 to <65% OR 1.61 (95% CI 1.26-2.04); <55% OR 5.22 (3.42-7.95))
      as did increasing age (reference <50: 50-59 OR 1.58 (1.17-2.12), 60-69 OR 1.91
      (1.42-2.57)) 70+ OR 2.72 (1.82-4.08)) and prior use of cardiac medication (OR
      8.46 (4.69-15.25)). >3 cycles of anthracycline was associated with higher risk of
      cardiac events only for 12-month patients (OR 1.41 (1.04-1.90)), and not for 6
      month patients (OR 1.28 (0.91-1.79)). CONCLUSIONS: We demonstrate significantly
      fewer cardiac events from 6 months of adjuvant trastuzumab compared with that
      from 12 months. This cardiac signal adds importance to the question of the
      optimum duration of adjuvant trastuzumab treatment. If 6 months is proven to have
      non-inferior outcomes to 12 months treatment, these data would support 6 months
      as the standard of care.

PMID- 27875517
TI  - Adjuvant chemotherapy and HER-2-directed therapy for early-stage breast cancer in
      the elderly.
AB  - There is a lack of sufficient evidence-based data defining the optimal adjuvant
      systemic therapies in older women. Recommendations are mainly based on
      retrospective studies, subgroup analyses within larger randomised trials and
      expert opinion. Treatment decisions should consider the functional fitness of the
      patient, co-morbidities, in addition to chronological age with the aim to balance
      risks and potential benefits from treatment(s). In this review, we discuss
      assessment tools to aid clinicians to select elderly patients who are 'fit' for
      chemotherapy, and review the literature on the use of chemotherapy and of the
      anti-HER 2 antibody trastuzumab in this population. We will also review two
      commonly used prediction models to assess their accuracy in predicting survival
      outcomes in elderly patients. Ongoing clinical trials specifically focusing on
      older patients may help to clarify the absolute benefits and risks of adjuvant
      systemic therapy in this age group.

PMID- 27875518
TI  - A national cluster-randomised controlled trial to examine the effect of enhanced
      reminders on the socioeconomic gradient in uptake in bowel cancer screening.
AB  - BACKGROUND: The NHS Bowel Cancer Screening Programme in England offers biennial
      guaiac faecal occult blood testing (gFOBt). There is a socioeconomic gradient in
      participation and socioeconomically disadvantaged groups have worse colorectal
      cancer survival than more advantaged groups. We compared the effectiveness and
      cost of an enhanced reminder letter with the usual reminder letter on overall
      uptake of gFOBt and the socioeconomic gradient in uptake. METHODS: We enhanced
      the usual reminder by including a heading 'A reminder to you' and a short
      paragraph restating the offer of screening in simple language. We undertook a
      cluster-randomised trial of all 168 480 individuals who were due to receive a
      reminder over 20 days in 2013. Randomisation was based on the day of invitation.
      Blinding of individuals was not possible, but the possibility of bias was minimal
      owing to the lack of direct contact with participants. The enhanced reminder was
      sent to 78 067 individuals and 90 413 received the usual reminder. The primary
      outcome was the proportion of people adequately screened and its variation by
      quintile of Index of Multiple Deprivation. Data were analysed by logistic
      regression with conservative variance estimates to take account of cluster
      randomisation. RESULTS: There was a small but statistically significant (P=0.001)
      increase in participation with the enhanced reminder (25.8% vs 25.1%). There was
      significant (P=0.005) heterogeneity of the effect by socioeconomic status with an
      11% increase in the odds of participation in the most deprived quintile (from
      13.3 to 14.1%) and no increase in the least deprived. We estimated that
      implementing the enhanced reminder nationally could result in up to 80 more
      people with high or intermediate risk colorectal adenomas and up to 30 more
      cancers detected each year if it were implemented nationally. The intervention
      incurred a small one-off cost of L78 000 to modify the reminder letter.
      CONCLUSIONS: The enhanced reminder increases overall uptake and reduces the
      socioeconomic gradient in bowel cancer screening participation at little
      additional cost.

PMID- 27875519
TI  - Expression of somatostatin receptors 2 and 5 in circulating tumour cells from
      patients with neuroendocrine tumours.
AB  - BACKGROUND: Neuroendocrine tumours (NET) overexpress somatostatin receptors
      (SSTR) that can be targeted for therapy. Somatostatin receptor expression is
      routinely measured by molecular imaging but the resolution is insufficient to
      define heterogeneity. We hypothesised that SSTR expression could be measured on
      circulating tumour cells (CTCs) and used to investigate heterogeneity of
      expression and track changes during therapy. METHODS: MCF-7 cells were
      transfected with SSTR2 or 5 and spiked into donor blood for analysis by
      CellSearch. Optimum anti-SSTR antibody concentration and exposure time were
      determined, and flow cytometry was used to evaluate assay sensitivity. For
      clinical evaluation, blood was analysed by CellSearch, and SSTR2/5
      immunohistochemistry was performed on matched tissue samples. RESULTS: Flow
      cytometry confirmed CellSearch was sensitive and that detection of SSTR was
      unaffected by the presence of somatostatin analogue up to a concentration of 100
      ng ml-l. Thirty-one NET patients were recruited: grade; G1 (29%), G2 (45%), G3
      (13%), primary site; midgut (58%), pancreatic (39%). Overall, 87% had SSTR
      positive tumours according to somatostatin receptor scintigraphy or 68-Ga-DOTATE
      PET/CT. Circulating tumour cells were detected in 21 out of 31 patients (68%), of
      which 33% had evidence of heterogeneous expression of either SSTR2 (n=5) or SSTR5
      (n=2). CONCLUSIONS: Somatostatin receptors 2 and 5 are detectable on CTCs from
      NET patients and may be a useful biomarker for evaluating SSTR-targeted therapies
      and this is being prospectively evaluated in the Phase IV CALMNET trial
      (NCT02075606).

PMID- 27875521
TI  - Trastuzumab cardiotoxiciy: the age-old balance of risk and benefit.

PMID- 27875520
TI  - The cell-autonomous mechanisms underlying the activity of metformin as an
      anticancer drug.
AB  - The biguanide drug metformin profoundly affects cell metabolism, causing an
      impairment of the cell energy balance and triggering a plethora of pleiotropic
      effects that vary depending on the cellular or environmental context.
      Interestingly, a decade ago, it was observed that metformin-treated diabetic
      patients have a significantly lower cancer risk. Although a variety of in vivo
      and in vitro observations emphasising the role of metformin as anticancer drug
      have been reported, the underlying mechanisms are still poorly understood. Here,
      we discuss our current understanding of the molecular mechanisms that are
      perturbed by metformin treatment and that might be relevant to understand its
      antitumour activities. We focus on the cell-autonomous mechanisms modulating
      growth and death of cancer cells.

PMID- 27875523
TI  - A protein fragment derived from DNA-topoisomerase I as a novel tumour-associated
      antigen for the detection of early stage carcinoma.
AB  - BACKGROUND: The production of autoantibodies against tumour-associated antigens
      (TAAs) is believed to reflect greater immunologic reactivity in cancer patients
      and enhanced immune surveillance for cancer cells. Over the past few decades, a
      number of different TAAs and their corresponding autoantibodies have been
      investigated. However, positive frequency of autoantibody detection in cancer
      patients has been relatively low. Here we describe a novel TAA that was a
      fragment derived from human DNA-topoiomerase I and an autoantibody against the
      novel TAA with relatively high positive frequency in the sera of early-stage non
      small-cell lung cancer (NSCLC), gastric cancer (GC), colorectal cancer (CRC) and
      oesophageal squamous cell carcinoma (ESCC). METHODS: Serologic enzyme-linked
      immunosorbent assay (ELISA) and western blot were used to discover a novel TAA
      with a molecular weight of 48 kDa separated by ion exchange chromatography.
      Autoantibody ELISA, immnohistochemistry and immunofluorescent staining,
      recombinant protein cloning/expression and western blot were used to identify the
      novel TAA. The association of the autoantibody against the novel TAA with early
      stage carcinoma was explored by screening 203 stage I/II patients and 170 stage
      III/IV patients with NSCLC, GC, CRC or ESCC. RESULTS: We identified the novel TAA
      as a fragment derived from human DNA-topoiomerase I (TOP1). We found that the
      novel TAA induced specific autoantibodies with a high prevalence that ranged from
      58 to 72% in some of the most common types of cancer. We observed that the immune
      response against the novel TAA was associated with early stage ESCC, GC, CRC and
      NSCLC. CONCLUSIONS: The findings in this study suggest that the autoantibody
      against the novel TAA may be a potential biomarker for use in the early detection
      and diagnosis of cancer.

PMID- 27875522
TI  - Hedgehog inhibition enhances efficacy of radiation and cisplatin in orthotopic
      cervical cancer xenografts.
AB  - BACKGROUND: The Hedgehog (Hh) pathway is upregulated in cervical cancer and
      associated with poor outcome. We explored the effects of Hh pathway inhibition in
      combination with RTCT in a patient derived orthotopic cervical cancer xenograft
      model (OCICx). METHODS: 5E1, a monoclonal antibody for SHH, or Sonidegib
      (LDE225), a clinical SMO inhibitor (Novartis) were added to RTCT. We investigated
      tumour growth delay, metastasis and GI toxicity using orthotopic cervical cancer
      xenografts models. The xenografts were treated with radiotherapy (15 * 2 Gy daily
      fractions over 3 weeks) and weekly cisplatin 4 mg kg-1 concurrently, with or
      without 5E1 or Sonidegib (LDE225). The Hh inhibitors were administered by
      subcutaneous injection (5E1; 20 mg kg-1 weekly for 3 weeks), or by oral gavage
      (Sonidegib; 60 mg kg-1 daily for 3 weeks). RESULTS: We observed that both Hh
      inhibitors administered with RTCT were well tolerated and showed increased tumour
      growth delay, and reduced metastasis, with no increase in acute GI-toxicity
      relative to RTCT alone. CONCLUSIONS: Our data suggest Hh can be a valid
      therapeutic target in cervical cancer and supports data suggesting a potential
      therapeutic role for targeting Hh in patients undergoing RTCT. This warrants
      further investigation in clinical trials.

PMID- 27875524
TI  - microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of
      XIAP.
AB  - BACKGROUND: microRNAs (miRNAs) have regulatory roles in various cellular
      processes, including apoptosis. Recently, X-linked inhibitor of apoptosis protein
      (XIAP) has been reported to be dysregulated in epithelial ovarian cancer (EOC).
      However, the mechanism underlying this dysregulation is largely unknown. METHODS:
      Using bioinformatics and a literature analysis, a panel of miRNAs dysregulated in
      EOC was chosen for further experimental confirmation from hundreds of miRNAs that
      were predicted to interact with the XIAP 3'UTR. A dual-luciferase reporter assay
      was employed to detect the interaction by cellular co-transfection of an miRNA
      expression vector and a reporter vector with the XIAP 3'UTR fused to a Renilla
      luciferase reporter. DAPI and TUNEL approaches were used to further determine the
      effects of an miR-137 mimic and inhibitor on cisplatin-induced apoptosis in
      ovarian cancer cells. RESULTS: We identified eight miRNAs by screening a panel of
      dysregulated miRNAs that may target the XIAP 3'UTR. The strongest inhibitory
      miRNA, miR-137, suppressed the activity of a luciferase reporter gene fused with
      the XIAP 3'UTR and decreased the levels of XIAP protein in SKOV3 ovarian cancer
      cells. Furthermore, forced expression of miR-137 increased cisplatin-induced
      apoptosis, and the depressed expression of miR-137 decreased cisplatin-induced
      apoptosis in SKOV3 and primary EOC cells. Consistently, the disruption of miR-137
      via CRISPR/Cas9 inhibited apoptosis and upregulated XIAP in A2780 cells.
      Furthermore, the effect of miR-137 on apoptosis could be rescued by XIAP in SKOV3
      cells. In addition, miR-137 expression is inversely correlated with the level of
      XIAP protein in both ovarian cancer tissues and cell lines. CONCLUSIONS: Our data
      suggest that multiple miRNAs can regulate XIAP via its 3'UTR. miR-137 can
      sensitise ovarian cancer cells to cisplatin-induced apoptosis, providing new
      insight into overcoming drug resistance in ovarian cancer.

PMID- 27875525
TI  - Precision medicine in cancer: challenges and recommendations from an EU-funded
      cervical cancer biobanking study.
AB  - BACKGROUND: Cervical cancer (CC) remains a leading cause of gynaecological cancer
      related mortality worldwide. CC pathogenesis is triggered when human
      papillomavirus (HPV) inserts into the genome, resulting in tumour suppressor gene
      inactivation and oncogene activation. Collecting tumour and blood samples is
      critical for identifying these genetic alterations. METHODS: BIO-RAIDs is the
      first prospective molecular profiling clinical study to include a substantial
      biobanking effort that used uniform high-quality standards and control of
      samples. In this European Union (EU)-funded study, we identified the challenges
      that were impeding the effective implementation of such a systematic and
      comprehensive biobanking effort. RESULTS: The challenges included a lack of
      uniform international legal and ethical standards, complexities in clinical and
      molecular data management, and difficulties in determining the best technical
      platforms and data analysis techniques. Some difficulties were encountered by all
      investigators, while others affected only certain institutions, regions, or
      countries. CONCLUSIONS: The results of the BIO-RAIDs programme highlight the need
      to facilitate and standardise regulatory procedures, and we feel that there is
      also a need for international working groups that make recommendations to
      regulatory bodies, governmental funding agencies, and academic institutions to
      achieve a proficient biobanking programme throughout EU countries. This
      represents the first step in precision medicine.

PMID- 27875526
TI  - Caphosol for prevention of oral mucositis in pediatric myeloablative
      haematopoietic cell transplantation.
AB  - BACKGROUND: The primary objective was to determine whether topically administered
      Caphosol, rinsed orally four times daily at the initiation of conditioning,
      reduces the duration of severe oral mucositis (OM) compared with placebo among
      children and adolescents undergoing haematopoietic cell transplantation (HCT).
      METHODS: This was a Children's Oncology Group multicentre randomised double
      blinded placebo-controlled clinical trial. Patients between the ages of 4 and 21
      years who were scheduled to undergo myeloablative HCT for any indication were
      randomised to Caphosol or placebo saline rinses four times daily from initiation
      of conditioning through day +20. Subjects were assessed daily for OM using the
      World Health Organisation (WHO) Oral Toxicity Scale, Mouth Pain Categorical Scale
      (0-10) and the Oral Mucositis Daily Questionnaire (OMDQ). The primary end point
      was duration of severe OM (WHO ?3). RESULTS: The study enrolled 220 participants
      with a median age of 13.7 years (range 4.0-21.9); 163 (74%) received allogeneic
      HCT. The mean (+/-s.d.) duration of severe OM was not reduced among Caphosol
      (4.5+/-5.0 days) vs placebo (4.5+/-4.8; P=0.99) recipients. The incidence of
      severe OM in the Caphosol and placebo arms was 63% (57 out of 91) and 68% (62 out
      of 91), respectively (P=0.44). There were no significant differences in any of
      the secondary end points between the groups. CONCLUSIONS: Caphosol did not reduce
      severe OM when compared with placebo among children and adolescents undergoing
      myeloablative HCT. Studies to identify effective interventions for OM are needed
      in this population.

PMID- 27875527
TI  - Non-classic EGFR mutations in a cohort of Dutch EGFR-mutated NSCLC patients and
      outcomes following EGFR-TKI treatment.
AB  - BACKGROUND: Data on non-small-cell lung cancer (NSCLC) patients with non-classic
      epidermal growth factor receptor (EGFR) mutations are scarce, especially in non
      Asian populations. The purpose of this study was to evaluate prevalence, clinical
      characteristics and outcome on EGFR-TKI treatment according to type of EGFR
      mutation in a Dutch cohort of NSCLC patients. METHODS: We retrospectively
      evaluated a cohort of 240 EGFR-mutated NSCLC patients. Data on demographics,
      clinical and tumour-related features, EGFR-TKI treatment and clinical outcome
      were collected and compared between patients with classic EGFR mutations, EGFR
      exon 20 insertions and other uncommon EGFR mutations. RESULTS: Classic EGFR
      mutations were detected in 186 patients (77.5%) and non-classic EGFR mutations in
      54 patients (22.5%); 23 patients with an exon 20 insertion (9.6%) and 31 patients
      with an uncommon EGFR mutation (12.9%). Median progression-free survival (PFS)
      and overall survival (OS) on EGFR-TKI treatment were 2.9 and 9.7 months,
      respectively, for patients with an EGFR exon 20 insertion, and 6.4 and 20.2
      months, respectively, for patients with an uncommon EGFR mutation. Patients with
      a double uncommon EGFR mutation that included G719X/L861Q/S768I had longer PFS
      and OS on EGFR-TKI treatment compared with patients with a single
      G719X/L861Q/S768I EGFR mutation (both P=0.02). CONCLUSIONS: In our Dutch cohort,
      prevalence and genotype distribution of non-classic EGFR mutations were in
      accordance with previously reported data. The PFS and OS on EGFR-TKI treatment in
      patients with an uncommon EGFR mutation were shorter compared with patients with
      classic EGFR mutations, but varied among different uncommon EGFR mutations.

PMID- 27875528
TI  - Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of
      Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.
AB  - BACKGROUND: Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine
      (SP) plus amodiaquine (AQ), given each month during the transmission season, is
      recommended for children living in areas of the Sahel where malaria transmission
      is highly seasonal. The recommendation for SMC is currently limited to children
      under five years of age, but, in many areas of seasonal transmission, the burden
      in older children may justify extending this age limit. This study was done to
      determine the effectiveness of SMC in Senegalese children up to ten years of age.
      METHODS AND FINDINGS: SMC was introduced into three districts over three years in
      central Senegal using a stepped-wedge cluster-randomised design. A census of the
      population was undertaken and a surveillance system was established to record all
      deaths and to record all cases of malaria seen at health facilities. A
      pharmacovigilance system was put in place to detect adverse drug reactions. Fifty
      four health posts were randomised. Nine started implementation of SMC in 2008, 18
      in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first
      year of implementation, SMC was delivered to children aged 3-59 months; the age
      range was then extended for the latter two years of the study to include children
      up to 10 years of age. Cluster sample surveys at the end of each transmission
      season were done to measure coverage of SMC and the prevalence of parasitaemia
      and anaemia, to monitor molecular markers of drug resistance, and to measure
      insecticide-treated net (ITN) use. Entomological monitoring and assessment of
      costs of delivery in each health post and of community attitudes to SMC were also
      undertaken. About 780,000 treatments were administered over three years. Coverage
      exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and
      control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and
      1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate
      ratio [SMC: no SMC] was 0.90, 95% CI 0.68-1.2, p = 0.496). A reduction of 60%
      (95% CI 54%-64%, p < 0.001) in the incidence of malaria cases confirmed by a
      rapid diagnostic test (RDT) and a reduction of 69% (95% CI 65%-72%, p < 0.001) in
      the number of treatments for malaria (confirmed and unconfirmed) was observed in
      children. In areas where SMC was implemented, incidence of confirmed malaria in
      adults and in children too old to receive SMC was reduced by 26% (95% CI 18%-33%,
      p < 0.001) and the total number of treatments for malaria (confirmed and
      unconfirmed) in these older age groups was reduced by 29% (95% CI 21%-35%, p <
      0.001). One hundred and twenty-three children were admitted to hospital with a
      diagnosis of severe malaria, with 64 in control areas and 59 in SMC areas,
      showing a reduction in the incidence rate of severe disease of 45% (95% CI 5%
      68%, p = 0.031). Estimates of the reduction in the prevalence of parasitaemia at
      the end of the transmission season in SMC areas were 68% (95% CI 35%-85%) p =
      0.002 in 2008, 84% (95% CI 58%-94%, p < 0.001) in 2009, and 30% (95% CI -130%
      79%, p = 0.56) in 2010. SMC was well tolerated with no serious adverse reactions
      attributable to SMC drugs. Vomiting was the most commonly reported mild adverse
      event but was reported in less than 1% of treatments. The average cost of
      delivery was US$0.50 per child per month, but varied widely depending on the size
      of the health post. Limitations included the low rate of mortality, which limited
      our ability to detect an effect on this endpoint. CONCLUSIONS: SMC substantially
      reduced the incidence of outpatient cases of malaria and of severe malaria in
      children, but no difference in all-cause mortality was observed. Introduction of
      SMC was associated with an overall reduction in malaria incidence in untreated
      age groups. In many areas of Africa with seasonal malaria, there is a substantial
      burden in older children that could be prevented by SMC. SMC in older children is
      well tolerated and effective and can contribute to reducing malaria transmission.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00712374.

PMID- 27875529
TI  - CD4+ T Cells Are as Protective as CD8+ T Cells against Rickettsia typhi Infection
      by Activating Macrophage Bactericidal Activity.
AB  - Rickettsia typhi is an intracellular bacterium that causes endemic typhus, a
      febrile disease that can be fatal due to complications including pneumonia,
      hepatitis and meningoencephalitis, the latter being a regular outcome in T and B
      cell-deficient C57BL/6 RAG1-/- mice upon Rickettsia typhi infection. Here, we
      show that CD4+ TH1 cells that are generated in C57BL/6 mice upon R. typhi
      infection are as protective as cytotoxic CD8+ T cells. CD4+- as well as CD8+
      deficient C57BL/6 survived the infection without showing symptoms of disease at
      any point in time. Moreover, adoptively transferred CD8+ and CD4+ immune T cells
      entered the CNS of C57BL/6 RAG1-/- mice with advanced infection and both
      eradicated the bacteria. However, immune CD4+ T cells protected only
      approximately 60% of the animals from death. They induced the expression of iNOS
      in infiltrating macrophages as well as in resident microglia in the CNS which can
      contribute to bacterial killing but also accelerate pathology. In vitro immune
      CD4+ T cells inhibited bacterial growth in infected macrophages which was in part
      mediated by the release of IFNgamma. Collectively, our data demonstrate that CD4+
      T cells are as protective as CD8+ T cells against R. typhi, provided that CD4+
      TH1 effector cells are present in time to support bactericidal activity of
      phagocytes via the release of IFNgamma and other factors. With regard to
      vaccination against TG Rickettsiae, our findings suggest that the induction of
      CD4+ TH1 effector cells is sufficient for protection.

PMID- 27875530
TI  - Validity of a Minimally Invasive Autopsy for Cause of Death Determination in
      Adults in Mozambique: An Observational Study.
AB  - BACKGROUND: There is an urgent need to identify tools able to provide reliable
      information on the cause of death in low-income regions, since current methods
      (verbal autopsy, clinical records, and complete autopsies) are either inaccurate,
      not feasible, or poorly accepted. We aimed to compare the performance of a
      standardized minimally invasive autopsy (MIA) approach with that of the gold
      standard, the complete diagnostic autopsy (CDA), in a series of adults who died
      at Maputo Central Hospital in Mozambique. METHODS AND FINDINGS: In this
      observational study, coupled MIAs and CDAs were performed in 112 deceased
      patients. The MIA analyses were done blindly, without knowledge of the clinical
      data or the results of the CDA. We compared the MIA diagnosis with the CDA
      diagnosis of cause of death. CDA diagnoses comprised infectious diseases (80;
      71.4%), malignant tumors (16; 14.3%), and other diseases, including non
      infectious cardiovascular, gastrointestinal, kidney, and lung diseases (16;
      14.3%). A MIA diagnosis was obtained in 100/112 (89.2%) cases. The overall
      concordance between the MIA diagnosis and CDA diagnosis was 75.9% (85/112). The
      concordance was higher for infectious diseases and malignant tumors (63/80
      [78.8%] and 13/16 [81.3%], respectively) than for other diseases (9/16; 56.2%).
      The specific microorganisms causing death were identified in the MIA in 62/74
      (83.8%) of the infectious disease deaths with a recognized cause. The main
      limitation of the analysis is that both the MIA and the CDA include some degree
      of expert subjective interpretation. CONCLUSIONS: A simple MIA procedure can
      identify the cause of death in many adult deaths in Mozambique. This tool could
      have a major role in improving the understanding and surveillance of causes of
      death in areas where infectious diseases are a common cause of mortality.

PMID- 27875531
TI  - Loss of C9orf72 Enhances Autophagic Activity via Deregulated mTOR and TFEB
      Signaling.
AB  - The most common cause of the neurodegenerative diseases amyotrophic lateral
      sclerosis and frontotemporal dementia is a hexanucleotide repeat expansion in
      C9orf72. Here we report a study of the C9orf72 protein by examining the
      consequences of loss of C9orf72 functions. Deletion of one or both alleles of the
      C9orf72 gene in mice causes age-dependent lethality phenotypes. We demonstrate
      that C9orf72 regulates nutrient sensing as the loss of C9orf72 decreases
      phosphorylation of the mTOR substrate S6K1. The transcription factor EB (TFEB), a
      master regulator of lysosomal and autophagy genes, which is negatively regulated
      by mTOR, is substantially up-regulated in C9orf72 loss-of-function animal and
      cellular models. Consistent with reduced mTOR activity and increased TFEB levels,
      loss of C9orf72 enhances autophagic flux, suggesting that C9orf72 is a negative
      regulator of autophagy. We identified a protein complex consisting of C9orf72 and
      SMCR8, both of which are homologous to DENN-like proteins. The depletion of
      C9orf72 or SMCR8 leads to significant down-regulation of each other's protein
      level. Loss of SMCR8 alters mTOR signaling and autophagy. These results
      demonstrate that the C9orf72-SMCR8 protein complex functions in the regulation of
      metabolism and provide evidence that loss of C9orf72 function may contribute to
      the pathogenesis of relevant diseases.

PMID- 27875534
TI  - Seasonal Malaria Chemoprevention: An Evolving Research Paradigm.
AB  - Robert W. Snow discusses the importance of empirical evidence, such as that
      provided in the trial published this week by Milligan and colleagues, in guiding
      malaria control in Africa.

PMID- 27875533
TI  - Pulmonary Arterial Capacitance Predicts Cardiac Events in Pulmonary Hypertension
      Due to Left Heart Disease.
AB  - BACKGROUND: Although pulmonary hypertension due to left heart disease (LHD-PH)
      accounts for the largest proportion of pulmonary hypertension, few reports on the
      epidemiological analysis of LHD-PH exist. Recently, pulmonary arterial
      capacitance (PAC) has attracted attention as a possible factor of right
      ventricular afterload along with pulmonary vascular resistance. We therefore
      investigated the clinical significance of PAC in LHD-PH. METHODS: The subject
      consisted of 252 LHD-PH patients (145 men, mean age 63.4 +/- 14.7 years)
      diagnosed by right heart catheterization. PAC was estimated by the ratio between
      stroke volume and pulmonary arterial pulse pressure. Patients were classified
      into four groups according to the PAC (1st quartile was 0.74 to 1.76 ml/mmHg, the
      2nd quartile 1.77 to 2.53 ml/mmHg, the 3rd quartile 2.54 to 3.59 ml/mmHg, and the
      4th quartile 3.61 to 12.14 ml/mmHg). The end-points were defined as
      rehospitalization due to worsening heart failure and/or cardiac death. The Cox
      proportional hazard regression model was used to determine what variables were
      associated with cardiac events. RESULTS: The patients in the 1st quartile had the
      lowest cardiac index and stroke volume index, and the highest mean pulmonary
      arterial pressure, mean pulmonary capillary wedge pressure, and pulmonary
      vascular resistance compared with the 2nd, 3rd, and 4th quartiles. Fifty-four
      patients experienced cardiac events during the follow-up period (median 943
      days). The event-free rate of the 1st quartile was significantly lower than that
      of the 3rd and 4th quartiles (66.7% vs 82.5% [3rd quartile], P = 0.008; and 92.1%
      [4th quartile], P < 0.001). The Cox hazard analysis revealed that PAC was
      significantly associated with cardiac events (HR 0.556, 95% CI 0.424-0.730, P <
      0.001). CONCLUSION: PAC is useful in the prediction of cardiac event risk in LHD
      PH patients.

PMID- 27875535
TI  - Minimally Invasive Autopsy: A New Paradigm for Understanding Global Health?
AB  - Peter Byass reflects on the potential niche for minimally invasive autopsies in
      determining cause-of-death in low- and middle-income countries.

PMID- 27875532
TI  - Willingness to Know the Cause of Death and Hypothetical Acceptability of the
      Minimally Invasive Autopsy in Six Diverse African and Asian Settings: A Mixed
      Methods Socio-Behavioural Study.
AB  - BACKGROUND: The minimally invasive autopsy (MIA) is being investigated as an
      alternative to complete diagnostic autopsies for cause of death (CoD)
      investigation. Before potential implementation of the MIA in settings where post
      mortem procedures are unusual, a thorough assessment of its feasibility and
      acceptability is essential. METHODS AND FINDINGS: We conducted a socio
      behavioural study at the community level to understand local attitudes and
      perceptions related to death and the hypothetical feasibility and acceptability
      of conducting MIAs in six distinct settings in Gabon, Kenya, Mali, Mozambique,
      and Pakistan. A total of 504 interviews (135 key informants, 175 health providers
      [including formal health professionals and traditional or informal health
      providers], and 194 relatives of deceased people) were conducted. The constructs
      "willingness to know the CoD" and "hypothetical acceptability of MIAs" were
      quantified and analysed using the framework analysis approach to compare the
      occurrence of themes related to acceptability across participants. Overall, 75%
      (379/504) of the participants would be willing to know the CoD of a relative. The
      overall hypothetical acceptability of MIA on a relative was 73% (366/504). The
      idea of the MIA was acceptable because of its perceived simplicity and rapidity
      and particularly for not "mutilating" the body. Further, MIAs were believed to
      help prevent infectious diseases, address hereditary diseases, clarify the CoD,
      and avoid witchcraft accusations and conflicts within families. The main concerns
      regarding the procedure included the potential breach of confidentiality on the
      CoD, the misperception of organ removal, and the incompatibility with some
      religious beliefs. Formal health professionals were concerned about possible
      contradictions between the MIA findings and the clinical pre-mortem diagnoses.
      Acceptability of the MIA was equally high among Christian and Islamic
      communities. However, in the two predominantly Muslim countries, MIA
      acceptability was higher in Mali than in Pakistan. While the results of the study
      are encouraging for the potential use of the MIA for CoD investigation in low
      income settings, they remain hypothetical, with a need for confirmation with real
      life MIA implementation and in populations beyond Health and Demographic
      Surveillance System areas. CONCLUSIONS: This study showed a high level of
      interest in knowing the CoD of a relative and a high hypothetical acceptability
      of MIAs as a tool for CoD investigation across six distinct settings. These
      findings anticipate potential barriers and facilitators, both at the health
      facility and community level, essential for local tailoring of recommendations
      for future MIA implementation.

PMID- 27875536
TI  - Capturing Dynamics of Biased Attention: Are New Attention Variability Measures
      the Way Forward?
AB  - BACKGROUND: New indices, calculated on data from the widely used Dot Probe Task,
      were recently proposed to capture variability in biased attention allocation. We
      observed that it remains unclear which data pattern is meant to be indicative of
      dynamic bias and thus to be captured by these indices. Moreover, we hypothesized
      that the new indices are sensitive to SD differences at the response time (RT)
      level in the absence of bias. METHOD: Randomly generated datasets were analyzed
      to assess properties of the Attention Bias Variability (ABV) and Trial Level Bias
      Score (TL-BS) indices. Sensitivity to creating differences in 1) RT standard
      deviation, 2) mean RT, and 3) bias magnitude were assessed. In addition, two
      possible definitions of dynamic attention bias were explored by creating
      differences in 4) frequency of bias switching, and 5) bias magnitude in the
      presence of constant switching. RESULTS: ABV and TL-BS indices were found highly
      sensitive to increasing SD at the response time level, insensitive to increasing
      bias, linearly sensitive to increasing bias magnitude in the presence of bias
      switches, and non-linearly sensitive to increasing the frequency of bias
      switches. The ABV index was also found responsive to increasing mean response
      times in the absence of bias. CONCLUSION: Recently proposed DPT derived
      variability indices cannot uncouple measurement error from bias variability.
      Significant group differences may be observed even if there is no bias present in
      any individual dataset. This renders the new indices in their current form unfit
      for empirical purposes. Our discussion focuses on fostering debate and ideas for
      new research to validate the potentially very important notion of biased
      attention being dynamic.

PMID- 27875537
TI  - Effect of L-Tryptophan and L-Leucine on Gut Hormone Secretion, Appetite Feelings
      and Gastric Emptying Rates in Lean and Non-Diabetic Obese Participants: A
      Randomized, Double-Blind, Parallel-Group Trial.
AB  - BACKGROUND/OBJECTIVES: Gut hormones such as cholecystokinin (CCK) and glucagon
      like peptide-1 (GLP-1) play a role as satiation factors. Strategies to enhance
      satiation peptide secretion could provide a therapeutic approach for obesity.
      Carbohydrates and lipids have been extensively investigated in relation to
      peptide release. In contrast, the role of proteins or amino acids is less clear.
      Our aim was to compare the effects of the amino acids L-tryptophan (L-trp) and L
      leucine (L-leu) separately on gastric emptying and gut peptide secretion.
      PARTICIPANTS/METHODS: The study was conducted as a randomized (balanced), double
      blind, parallel-group trial. A total of 10 lean and 10 non-diabetic obese
      participants were included. Participants received intragastric loads of L-trp
      (0.52 g and 1.56 g) and L-leu (1.56 g), dissolved in 300 mL tap water; 75 g
      glucose and 300 mL tap water served as control treatments. RESULTS: Results of
      the study are: i) L-trp at the higher dose stimulates CCK release (p = 0.0018),
      and induces a significant retardation in gastric emptying (p = 0.0033); ii) L-trp
      at the higher dose induced a small increase in GLP-1 secretion (p = 0.0257); iii)
      neither of the amino acids modulated subjective appetite feelings; and iv) the
      two amino acids did not alter insulin or glucose concentrations. CONCLUSIONS: L
      trp is a luminal regulator of CCK release with effects on gastric emptying, an
      effect that could be mediated by CCK. L-trp's effect on GLP-1 secretion is only
      minor. At the doses given, the two amino acids did not affect subjective appetite
      feelings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02563847.

PMID- 27875538
TI  - Seasonal Cyclicity in Trace Elements and Stable Isotopes of Modern Horse Enamel.
AB  - The study of stable isotopes in fossil bioapatite has yielded useful results and
      has shown that bioapatites are able to faithfully record paleo-environmental and
      paleo-climatic parameters from archeological to geological timescales. In an
      effort to establish new proxies for the study of bioapatites, intra-tooth records
      of enamel carbonate stable isotope ratios from a modern horse are compared with
      trace element profiles measured using laboratory micro X-Ray Fluorescence
      scanning. Using known patterns of tooth eruption and the relationship between
      stable oxygen isotopes and local temperature seasonality, an age model is
      constructed that links records from six cheek upper right teeth from the second
      premolar to the third molar. When plotted on this age model, the trace element
      ratios from horse tooth enamel show a seasonal pattern with a small shift in
      phase compared to stable oxygen isotope ratios. While stable oxygen and carbon
      isotopes in tooth enamel are forced respectively by the state of the hydrological
      cycle and the animal's diet, we argue that the seasonal signal in trace elements
      reflects seasonal changes in dust intake and diet of the animal. The latter
      explanation is in agreement with seasonal changes observed in carbon isotopes of
      the same teeth. This external forcing of trace element composition in mammal
      tooth enamel implies that trace element ratios may be used as proxies for
      seasonal changes in paleo-environment and paleo-diet.

PMID- 27875539
TI  - Secular Trends in Admissions and Mortality Rates from Diabetes Mellitus in the
      Central Belt of Ghana: A 31-Year Review.
AB  - INTRODUCTION: Diabetes Mellitus is currently a leading cause of morbidity and
      mortality throughout the world, particularly in sub-Saharan Africa where a
      significant proportion of diabetes cases are now found. Longitudinal profiling of
      in-patient admissions and mortality trends from diabetes provide useful insights
      into the magnitude of the burden of diabetes, serve as a sentinel on the state of
      out-patient diabetes care and provide effective tools for planning, delivering
      and evaluating the health care needs relating to the disease in sub-Saharan
      Africa. OBJECTIVE: To evaluate the 31-year trend in diabetic admissions and
      mortality rates in central Ghana. METHODS: This is a retrospective analysis of
      data on diabetes admissions and deaths at a tertiary referral hospital in central
      Ghana between 1983 and 2014. Rates of diabetes admissions or deaths were
      expressed as diabetes admissions or deaths divided by the total number of
      admissions or deaths respectively. Yearly crude fatality rates for diabetes were
      calculated. Trends were analysed for in patient diabetes admissions and mortality
      for the period. Predictors of diabetes mortality were determined using multiple
      logistic regression. RESULTS: A total of 11,414 diabetes patients were admitted
      over the period with a female predominance; female:male ratio of 1.3:1.0. Over
      the study period, diabetes admission rates increased significantly from 2.36 per
      1000 admissions in 1983 to 14.94 per 1000 admissions in 2014 (p<0.0001for linear
      trend), representing a 633% rise over the 31-year period. In-patient diabetes
      fatality rates increased from 7.6 per 1000 deaths in 1983 to 30 per 1000 deaths
      in 2012. The average 28-day mortality rate was 18.5%. The median age of patients
      increased significantly over the period. So was the proportion of females
      admitted over the years. Predictors of in-patient mortality were increasing age-
      aOR of 1.23 (CI: 1.15-1.32) for age > 80 years compared with < 20 years,
      admissions in 2000s compared to 1980s-aOR of 1.56 (1.21-2.01), male gender-aOR of
      1.45 (1.19-1.61), the presence of glycemic complications such as ketoacidosis-
      aOR-2.67(CI: 2.21-3.21), hyperosmolar hyperglycemic states- aOR 1.52 (1.33-1.73)
      symptomatic hypoglycemia- aOR 1.64 (1.24-2.17) and presence of end organ
      complications including peripheral neuropathic ulcers- aOR 1.31 (1.12-1.56),
      nephropathy- aOR -1.11 (1.03-1.23), cerebrovascular disease-aOR-1.52 (1.32-1.98),
      coronary artery disease- aOR-3.21 (1.91-5.15) and peripheral artery disease- aOR
      1.15 (1.12-1.21) were associated with increased risk of death compared with
      normoglycemic diabetic admissions and admissions without end organ complications
      respectively. CONCLUSION: Diabetes admission and mortality rates have increased
      significantly over the past three decades in central Ghana. More intensive
      education on the risk factors for diabetes, acute diabetes care as well as
      instituting hospital guidelines for diabetes control and reduction of modifiable
      risk factors for diabetes are urgently needed to reduce the poor case fatality
      associated with diabetes in resource-limited settings.

PMID- 27875540
TI  - Improving Preschoolers' Arithmetic through Number Magnitude Training: The Impact
      of Non-Symbolic and Symbolic Training.
AB  - The numerical cognition literature offers two views to explain numerical and
      arithmetical development. The unique-representation view considers the
      approximate number system (ANS) to represent the magnitude of both symbolic and
      non-symbolic numbers and to be the basis of numerical learning. In contrast, the
      dual-representation view suggests that symbolic and non-symbolic skills rely on
      different magnitude representations and that it is the ability to build an exact
      representation of symbolic numbers that underlies math learning. Support for
      these hypotheses has come mainly from correlative studies with inconsistent
      results. In this study, we developed two training programs aiming at enhancing
      the magnitude processing of either non-symbolic numbers or symbolic numbers and
      compared their effects on arithmetic skills. Fifty-six preschoolers were randomly
      assigned to one of three 10-session-training conditions: (1) non-symbolic
      training (2) symbolic training and (3) control training working on story
      understanding. Both numerical training conditions were significantly more
      efficient than the control condition in improving magnitude processing. Moreover,
      symbolic training led to a significantly larger improvement in arithmetic than
      did non-symbolic training and the control condition. These results support the
      dual-representation view.

PMID- 27875541
TI  - New Perspective on Impact of Folic Acid Supplementation during Pregnancy on
      Neurodevelopment/Autism in the Offspring Children - A Systematic Review.
AB  - It has been conclusively established that folic acid supplementation prior to and
      during early pregnancy (up to 12 weeks of gestation) can prevent neural tube
      defects (NTDs). We hypothesized that folate effects may extend from neuro
      structural defects to alterations in neuro-behavioural and emotional skills
      including autism spectrum disorders (ASDs) and other developmental disorders. The
      objective of this review was to comprehensively evaluate evidence on the impact
      of folic acid on neurodevelopment other than NTDs. We conducted an online search
      of relevant literature compiled by the National Library of Medicine from Medline
      and EMBASE (searched on Dec 31, 2014:
      http://www.ncbi.nlm.nih.gov/entrez/query/fcgi and http://www.elsevier.com/online
      tools/embase). We first created 3 files (search restricted to English literature)
      using the following key words: 1) folate or folic acid (171322 papers identified
      by this search); 2) maternal or pregnancy or pregnant or gestation or gestational
      or prenatal or antenatal or periconception or periconceptional (1349219 papers
      identified by this search); and 3) autism or autism spectrum disorders or
      developmental delay or development or neurodevelopment or mental or cognitive or
      language or personal-social or gross motor or fine motor or behaviour or
      intellectual or intelligence or Bayley Scale (8268145 papers identified by this
      search). We then merged the 3 files and reviewed the papers that addressed these
      three issues simultaneously. A total of 22 original papers that examined the
      association between folic acid supplementation in human pregnancy and
      neurodevelopment/autism were identified after the screening, with 15 studies
      showing a beneficial effect of folic acid supplementation on
      neurodevelopment/autism, 6 studies showed no statistically significant
      difference, while one study showed a harmful effect in > 5 mg folic acid
      supplementation/day during pregnancy. Folic acid supplementation in pregnancy may
      have beneficial effects on the neurodevelopment of children beyond its proven
      effect on NTDs.

PMID- 27875542
TI  - Educational Outreach with an Integrated Clinical Tool for Nurse-Led Non
      communicable Chronic Disease Management in Primary Care in South Africa: A
      Pragmatic Cluster Randomised Controlled Trial.
AB  - BACKGROUND: In many low-income countries, care for patients with non-communicable
      diseases (NCDs) and mental health conditions is provided by nurses. The benefits
      of nurse substitution and supplementation in NCD care in high-income settings are
      well recognised, but evidence from low- and middle-income countries is limited.
      Primary Care 101 (PC101) is a programme designed to support and expand nurses'
      role in NCD care, comprising educational outreach to nurses and a clinical
      management tool with enhanced prescribing provisions. We evaluated the effect of
      the programme on primary care nurses' capacity to manage NCDs. METHODS AND
      FINDINGS: In a cluster randomised controlled trial design, 38 public sector
      primary care clinics in the Western Cape Province, South Africa, were randomised.
      Nurses in the intervention clinics were trained to use the PC101 management tool
      during educational outreach sessions delivered by health department trainers and
      were authorised to prescribe an expanded range of drugs for several NCDs. Control
      clinics continued use of the Practical Approach to Lung Health and HIV/AIDS in
      South Africa (PALSA PLUS) management tool and usual training. Patients attending
      these clinics with one or more of hypertension (3,227), diabetes (1,842), chronic
      respiratory disease (1,157) or who screened positive for depression (2,466),
      totalling 4,393 patients, were enrolled between 28 March 2011 and 10 November
      2011. Primary outcomes were treatment intensification in the hypertension,
      diabetes, and chronic respiratory disease cohorts, defined as the proportion of
      patients in whom treatment was escalated during follow-up over 14 mo, and case
      detection in the depression cohort. Primary outcome data were analysed for 2,110
      (97%) intervention and 2,170 (97%) control group patients. Treatment
      intensification rates in intervention clinics were not superior to those in the
      control clinics (hypertension: 44% in the intervention group versus 40% in the
      control group, risk ratio [RR] 1.08 [95% CI 0.94 to 1.24; p = 0.252]; diabetes:
      57% versus 50%, RR 1.10 [0.97 to 1.24; p = 0.126]; chronic respiratory disease:
      14% versus 12%, RR 1.08 [0.75 to 1.55; p = 0.674]), nor was case detection of
      depression (18% versus 24%, RR 0.76 [0.53 to 1.10; p = 0.142]). No adverse
      effects of the nurses' expanded scope of practice were observed. Limitations of
      the study include dependence on self-reported diagnoses for inclusion in the
      patient cohorts, limited data on uptake of PC101 by users, reliance on process
      outcomes, and insufficient resources to measure important health outcomes, such
      as HbA1c, at follow-up. CONCLUSIONS: Educational outreach to primary care nurses
      to train them in the use of a management tool involving an expanded role in
      managing NCDs was feasible and safe but was not associated with treatment
      intensification or improved case detection for index diseases. This
      notwithstanding, the intervention, with adjustments to improve its effectiveness,
      has been adopted for implementation in primary care clinics throughout South
      Africa. TRIAL REGISTRATION: The trial is registered with Current Controlled
      Trials (ISRCTN20283604).

PMID- 27875543
TI  - Irisin Ameliorates Hypoxia/Reoxygenation-Induced Injury through Modulation of
      Histone Deacetylase 4.
AB  - Irisin is a recently identified myokine which brings increases in energy
      expenditure and contributes to the beneficial effects of exercise through the
      browning of white adipose tissues. However, its effects in the heart remains
      unknown. This study sought to determine the effects of irisin on
      hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and
      stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4
      overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia
      followed by one hour of reoxygenation in vitro in the presence or absence of
      irisin (5 ng/ml). Cell cytotoxicity, apoptosis, mitochondrial respiration, and
      mitochondrial permeability transition pore (mPTP) were determined. Western
      blotting was employed to determine active-caspase 3, annexin V, and HDAC4
      expression. As compared to wild type H9c2 group, HDAC4 overexpression remarkably
      led to a great increase in cell death as evident by the increased lactate
      dehydrogenase (LDH) leakage, ratio of caspase-3-positive cells as well as the
      upregulated levels of active-caspase 3 and annexin V shown by western blot
      analysis. In addition, HDAC4 overexpression also induced much severe
      mitochondrial dysfunction, as indicated by apoptotic mitochondria and increased
      mPTP. However, irisin treatment significantly attenuated all of these effects.
      Though irisin treatment did not influence the expression of HDAC4 at the
      transcriptional level, western blot analysis showed that HDAC4 protein levels
      decreased in a time-dependent way after administration of irisin, which is
      associated with the degradation of HDAC4 mediated by small ubiquitin-like
      modification (SUMO). Our results are the first to demonstrate that the protective
      effects of irisin in cardiomyoblasts exposed to hypoxia/reoxygenation might be
      associated with HDAC4 degradation.

PMID- 27875545
TI  - Study on Failure of Third-Party Damage for Urban Gas Pipeline Based on Fuzzy
      Comprehensive Evaluation.
AB  - Focusing on the diversity, complexity and uncertainty of the third-party damage
      accident, the failure probability of third-party damage to urban gas pipeline was
      evaluated on the theory of analytic hierarchy process and fuzzy mathematics. The
      fault tree of third-party damage containing 56 basic events was built by hazard
      identification of third-party damage. The fuzzy evaluation of basic event
      probabilities were conducted by the expert judgment method and using membership
      function of fuzzy set. The determination of the weight of each expert and the
      modification of the evaluation opinions were accomplished using the improved
      analytic hierarchy process, and the failure possibility of the third-party to
      urban gas pipeline was calculated. Taking gas pipelines of a certain large
      provincial capital city as an example, the risk assessment structure of the
      method was proved to conform to the actual situation, which provides the basis
      for the safety risk prevention.

PMID- 27875544
TI  - Extensive Association of Common Disease Variants with Regulatory Sequence.
AB  - Overlap between non-coding DNA regulatory sequences and common variant
      associations can help to identify specific cell and tissue types that are
      relevant for particular diseases. In a systematic manner, we analyzed variants
      from 94 genome-wide association studies (reporting at least 12 loci at p<5x10-8)
      by projecting them onto 466 epigenetic datasets (characterizing DNase I
      hypersensitive sites; DHSs) derived from various adult and fetal tissue samples
      and cell lines including many biological replicates. We were able to confirm many
      expected associations, such as the involvement of specific immune cell types in
      immune-related diseases and tissue types in diseases that affect specific organs,
      for example, inflammatory bowel disease and coronary artery disease. Other
      notable associations include adrenal glands in coronary artery disease, the
      immune system in Alzheimer's disease, and the kidney for bone marrow density. The
      association signals for some GWAS (for example, myopia or age at menarche) did
      not show a clear pattern with any of the cell or tissue types studied. In
      general, the identified variants from GWAS tend to be located outside coding
      regions. Altogether, we have performed an extensive characterization of GWAS
      signals in relation to cell and tissue-specific DHSs, demonstrating a key role
      for regulatory mechanisms in common diseases and complex traits.

PMID- 27875546
TI  - Evaluation of Control Strategies for Porcine Reproductive and Respiratory
      Syndrome (PRRS) in Swine Breeding Herds Using a Discrete Event Agent-Based Model.
AB  - The objective of this study was to develop a discrete event agent-based
      stochastic model to explore the likelihood of the occurrence of porcine
      reproductive and respiratory syndrome (PRRS) outbreaks in swine herds with
      different PRRS control measures in place. The control measures evaluated included
      vaccination with a modified-live attenuated vaccine and live-virus inoculation of
      gilts, and both were compared to a baseline scenario where no control measures
      were in place. A typical North American 1,000-sow farrow-to-wean swine herd was
      used as a model, with production and disease parameters estimated from the
      literature and expert opinion. The model constructed herein was not only able to
      capture individual animal heterogeneity in immunity to and shedding of the PRRS
      virus, but also the dynamic animal flow and contact structure typical in such
      herds under field conditions. The model outcomes included maximum number of
      females infected per simulation, and time at which that happened and the
      incidence of infected weaned piglets during the first year of challenge-virus
      introduction. Results showed that the baseline scenario produced a larger
      percentage of simulations resulting in outbreaks compared to the control
      scenarios, and interestingly some of the outbreaks occurred over long periods
      after virus introduction. The live-virus inoculation scenario showed promising
      results, with fewer simulations resulting in outbreaks than the other scenarios,
      but the negative impacts of maintaining a PRRS-positive population should be
      considered. Finally, under the assumptions of the current model, neither of the
      control strategies prevented the infection from spreading to the piglet
      population, which highlights the importance of maintaining internal biosecurity
      practices at the farrowing room level.

PMID- 27875547
TI  - How Accurate Is the Prediction of Maximal Oxygen Uptake with Treadmill Testing?
AB  - BACKGROUND: Cardiorespiratory fitness measured by treadmill testing has
      prognostic significance in determining mortality with cardiovascular and other
      chronic disease states. The accuracy of a recently developed method for
      estimating maximal oxygen uptake (VO2peak), the heart rate index (HRI), is
      dependent only on heart rate (HR) and was tested against oxygen uptake (VO2),
      either measured or predicted from conventional treadmill parameters (speed,
      incline, protocol time). METHODS: The HRI equation, METs = 6 x HRI- 5, where HRI
      = maximal HR/resting HR, provides a surrogate measure of VO2peak. Forty large
      scale treadmill studies were identified through a systematic search using
      MEDLINE, Google Scholar and Web of Science in which VO2peak was either measured
      (TM-VO2meas; n = 20) or predicted (TM-VO2pred; n = 20) based on treadmill
      parameters. All studies were required to have reported group mean data of both
      resting and maximal HRs for determination of HR index-derived oxygen uptake (HRI
      VO2). RESULTS: The 20 studies with measured VO2 (TM-VO2meas), involved 11,477
      participants (median 337) with a total of 105,044 participants (median 3,736) in
      the 20 studies with predicted VO2 (TM-VO2pred). A difference of only 0.4% was
      seen between mean (+/-SD) VO2peak for TM- VO2meas and HRI-VO2 (6.51+/-2.25 METs
      and 6.54+/-2.28, respectively; p = 0.84). In contrast, there was a highly
      significant 21.1% difference between mean (+/-SD) TM-VO2pred and HRI-VO2 (8.12+/
      1.85 METs and 6.71+/-1.92, respectively; p<0.001). CONCLUSION: Although mean TM
      VO2meas and HRI-VO2 were almost identical, mean TM-VO2pred was more than 20%
      greater than mean HRI-VO2.

PMID- 27875548
TI  - Accelerating Information Retrieval from Profile Hidden Markov Model Databases.
AB  - Profile Hidden Markov Model (Profile-HMM) is an efficient statistical approach to
      represent protein families. Currently, several databases maintain valuable
      protein sequence information as profile-HMMs. There is an increasing interest to
      improve the efficiency of searching Profile-HMM databases to detect sequence
      profile or profile-profile homology. However, most efforts to enhance searching
      efficiency have been focusing on improving the alignment algorithms. Although the
      performance of these algorithms is fairly acceptable, the growing size of these
      databases, as well as the increasing demand for using batch query searching
      approach, are strong motivations that call for further enhancement of information
      retrieval from profile-HMM databases. This work presents a heuristic method to
      accelerate the current profile-HMM homology searching approaches. The method
      works by cluster-based remodeling of the database to reduce the search space,
      rather than focusing on the alignment algorithms. Using different clustering
      techniques, 4284 TIGRFAMs profiles were clustered based on their similarities. A
      representative for each cluster was assigned. To enhance sensitivity, we proposed
      an extended step that allows overlapping among clusters. A validation benchmark
      of 6000 randomly selected protein sequences was used to query the clustered
      profiles. To evaluate the efficiency of our approach, speed and recall values
      were measured and compared with the sequential search approach. Using
      hierarchical, k-means, and connected component clustering techniques followed by
      the extended overlapping step, we obtained an average reduction in time of 41%,
      and an average recall of 96%. Our results demonstrate that representation of
      profile-HMMs using a clustering-based approach can significantly accelerate data
      retrieval from profile-HMM databases.

PMID- 27875549
TI  - The Synthetic beta-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor
      Growth and Metastasis via PI3K/AKT and STAT3 Pathways.
AB  - The beta-nitrostyrene family have been implicated for anti-cancer property.
      However, the pharmacological role of beta-nitrostyrene in esophageal cancer
      remain unclear. Here, a beta-nitrostyrene derivative, CYT-Rx20, was synthesized
      and assessed for its anti-cancer activities and underlying mechanism in
      esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by
      promoting apoptosis through activation of caspase cascade and poly(ADP-ribose)
      polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell
      migration and invasion by regulating the expression of epithelial to mesenchymal
      transition (EMT) markers. CYT-Rx20 decreased cell viability and migration through
      suppression of the PI3K/AKT and STAT3 pathways. Of note, the cytotoxicity and
      anti-migratory effect of CYT-Rx20 were enhanced by co-treatment with SC79 (AKT
      activator) or colivelin (STAT3 activator), suggesting the dependency of
      esophageal cancer cells on AKT and STAT3 for survival and migration, an oncogene
      addiction phenomenon. In xenograft tumor-bearing mice, CYT-Rx20 significantly
      reduced tumor growth of the implanted esophageal cancer cells accompanied by
      decreased Ki-67, phospho-AKT, and phospho-STAT3 expression. In orthotopic
      esophageal cancer mouse model, decreased tumor growth and lung metastasis with
      reduced Ki-67 and phospho-STAT3 expression were observed in mice treated with CYT
      Rx20. Together, our results suggest that CYT-Rx20 is a potential beta
      nitrostyrene-based anticancer compound against the tumor growth and metastasis of
      esophageal cancer.

PMID- 27875551
TI  - Crystal Structures of Group B Streptococcus Glyceraldehyde-3-Phosphate
      Dehydrogenase: Apo-Form, Binary and Ternary Complexes.
AB  - Glyceraldehyde 3-phosphate dehydrogenase or GAPDH is an evolutionarily conserved
      glycolytic enzyme. It catalyzes the two step oxidative phosphorylation of D
      glyceraldehyde 3-phosphate into 1,3-bisphosphoglycerate using inorganic phosphate
      and NAD+ as cofactor. GAPDH of Group B Streptococcus is a major virulence factor
      and a potential vaccine candidate. Moreover, since GAPDH activity is essential
      for bacterial growth it may serve as a possible drug target. Crystal structures
      of Group B Streptococcus GAPDH in the apo-form, two different binary complexes
      and the ternary complex are described here. The two binary complexes contained
      NAD+ bound to 2 (mixed-holo) or 4 (holo) subunits of the tetrameric protein. The
      structure of the mixed-holo complex reveals the effects of NAD+ binding on the
      conformation of the protein. In the ternary complex, the phosphate group of the
      substrate was bound to the new Pi site in all four subunits. Comparison with the
      structure of human GAPDH showed several differences near the adenosyl binding
      pocket in Group B Streptococcus GAPDH. The structures also reveal at least three
      surface-exposed areas that differ in amino acid sequence compared to the
      corresponding areas of human GAPDH.

PMID- 27875550
TI  - An Alternative Approach to ChIP-Seq Normalization Enables Detection of Genome
      Wide Changes in Histone H3 Lysine 27 Trimethylation upon EZH2 Inhibition.
AB  - Chromatin immunoprecipitation and DNA sequencing (ChIP-seq) has been instrumental
      in inferring the roles of histone post-translational modifications in the
      regulation of transcription, chromatin compaction and other cellular processes
      that require modulation of chromatin structure. However, analysis of ChIP-seq
      data is challenging when the manipulation of a chromatin-modifying enzyme
      significantly affects global levels of histone post-translational modifications.
      For example, small molecule inhibition of the methyltransferase EZH2 reduces
      global levels of histone H3 lysine 27 trimethylation (H3K27me3). However,
      standard ChIP-seq normalization and analysis methods fail to detect a decrease
      upon EZH2 inhibitor treatment. We overcome this challenge by employing an
      alternative normalization approach that is based on the addition of Drosophila
      melanogaster chromatin and a D. melanogaster-specific antibody into standard ChIP
      reactions. Specifically, the use of an antibody that exclusively recognizes the
      D. melanogaster histone variant H2Av enables precipitation of D. melanogaster
      chromatin as a minor fraction of the total ChIP DNA. The D. melanogaster ChIP-seq
      tags are used to normalize the human ChIP-seq data from DMSO and EZH2 inhibitor
      treated samples. Employing this strategy, a substantial reduction in H3K27me3
      signal is now observed in ChIP-seq data from EZH2 inhibitor treated samples.

PMID- 27875552
TI  - Varying Land-Use Has an Influence on Wattled and Grey Crowned Cranes' Abundance
      and Distribution in Driefontein Grasslands Important Bird Area, Zimbabwe.
AB  - Three species of cranes are distributed widely throughout southern Africa, but
      little is known about how they respond to the changes in land-use that have
      occurred in this region. This study assessed habitat preference of the two crane
      species across land-use categories of the self contained small scale commercial
      farms of 30 to 40 ha per household (A1), large scale commercial agriculture farms
      of > 50 ha per household (A2) and Old Resettlement, farms of < 5 ha per household
      with communal grazing land in Driefontein Grasslands Important Bird Area (IBA),
      Zimbabwe. The study further explored how selected explanatory (environmental)
      habitat variables influence crane species abundance. Crane bird counts and data
      on influencing environmental variables were collected between June and August
      2012. Our results show that varying land-use categories had an influence on the
      abundance and distribution of the Wattled Crane (Bugeranus carunculatus) and the
      Grey Crowned Crane (Belearica regulorum) across Driefontein Grasslands IBA. The
      Wattled Crane was widely distributed in the relatively undisturbed A2 farms while
      the Grey Crowned Crane was associated with the more disturbed land of A1 farms,
      Old Resettlement and its communal grazing land. Cyperus esculentus and percent
      (%) bare ground were strong environmental variables best explaining the observed
      patterns in Wattled Crane abundance across land-use categories. The pattern in
      Grey Crowned Crane abundance was best explained by soil penetrability, moisture
      and grass height variables. A holistic sustainable land-use management that takes
      into account conservation of essential habitats in Driefontein Grasslands IBA is
      desirable for crane populations and other wetland dependent species that include
      water birds.

PMID- 27875553
TI  - An Efficient Antipodal Cell Isolation Method for Screening of Cell Type-Specific
      Genes in Arabidopsis thaliana.
AB  - In flowering plants, the mature embryo sac consists of seven cells, namely two
      synergid cells and an egg cell at the micropylar end, one central cell, and three
      antipodal cells at the chalazal end. Excluding the antipodal cell, as a model for
      the study of cell fate determination and cell type specification, the roles of
      these embryo sac component cells in fertilization and seed formation have been
      widely investigated. At this time, little is known regarding the function of
      antipodal cells and their cell type-specific gene expression patterns. One reason
      for this is difficulties related to the observation and isolation of cells for
      detailed functional analyses. Here, we report a method for antipodal cell
      isolation and transcriptome analysis. We identified antipodal cell-specific
      marker line K44-1, and based on this marker line, established a procedure
      allowing us to isolate antipodal cells with both high quality and quantity. PCR
      validation of antipodal-specific genes from antipodal cell cDNA showed that the
      isolated cells are qualified and can be used for transcriptome analysis and
      screening of cell type-specific marker genes. The isolated cells could keep
      viable for a week in culture condition. This method can be used to efficiently
      isolate antipodal cells of high quality and will promote the functional
      investigation of antipodal cells in Arabidopsis thaliana. This increases our
      understanding of the molecular regulatory mechanism of antipodal cell
      specification.

PMID- 27875554
TI  - Incidence and Determinants of Ventilation Tubes in Denmark.
AB  - BACKGROUND AND OBJECTIVES: Many children are treated for recurrent acute otitis
      media and middle ear effusion with ventilation tubes (VT). The objectives are to
      describe the incidence of VT in Denmark during 1997-2011 from national register
      data, furthermore, to analyze the determinants for VT in the Copenhagen
      Prospective Studies on Asthma in Childhood2010 (COPSAC2010) birth cohort.
      METHODS: The incidence of VT in all children under 16 years from 1997-2011 were
      calculated in the Danish national registries. Determinants of VT were studied in
      the COPSAC2010 birth cohort of 700 children. RESULTS: Nationwide the prevalence
      of VT was 24% in children aged 0 to 3 three years, with a significant increase
      over the study period. For all children 0-15 years, the incidence of VT was
      35/1,000. In the VT population, 57% was male and 43% females. In the COPSAC2010
      birth cohort, the prevalence of VT during the first 3 years of life was 29%.
      Determinants of VT were: maternal history of middle ear disease; aHR 2.07, 95% CI
      [1.45-2.96] and siblings history of middle ear disease; aHR 3.02, [2.11-4.32].
      Paternal history of middle ear disease, presence of older siblings in the home
      and diagnosis of persistent wheeze were significant in the univariate analysis
      but the association did not persist after adjustment. CONCLUSION: The incidence
      of VT is still increasing in the youngest age group in Denmark, demonstrating the
      highest incidence recorded in the world. Family history of middle ear disease and
      older siblings are the main determinants for VT.

PMID- 27875555
TI  - Doping Polypyrrole Films with 4-N-Pentylphenylboronic Acid to Enhance Affinity
      towards Bacteria and Dopamine.
AB  - Here we demonstrate the use of a functional dopant as a fast and simple way to
      tune the chemical affinity and selectivity of polypyrrole films. More
      specifically, a boronic-functionalised dopant, 4-N-Pentylphenylboronic Acid
      (PBA), was used to provide to polypyrrole films with enhanced affinity towards
      diols. In order to prove the proposed concept, two model systems were explored:
      (i) the capture and the electrochemical detection of dopamine and (ii) the
      adhesion of bacteria onto surfaces. The chemisensor, based on overoxidised
      polypyrrole boronic doped film, was shown to have the ability to capture and
      retain dopamine, thus improving its detection; furthermore the chemisensor showed
      better sensitivity in comparison with overoxidised perchlorate doped films. The
      adhesion of bacteria, Deinococcus proteolyticus, Escherichia coli, Streptococcus
      pneumoniae and Klebsiella pneumoniae, onto the boric doped polypyrrole film was
      also tested. The presence of the boronic group in the polypyrrole film was shown
      to favour the adhesion of sugar-rich bacterial cells when compared with a control
      film (Dodecyl benzenesulfonate (DBS) doped film) with similar morphological and
      physical properties. The presented single step synthesis approach is simple and
      fast, does not require the development and synthesis of functional monomers, and
      can be easily expanded to the electrochemical, and possibly chemical, fabrication
      of novel functional surfaces and interfaces with inherent pre-defined sensing and
      chemical properties.

PMID- 27875556
TI  - MxA Is a Novel Regulator of Endosome-Associated Transcriptional Signaling by Bone
      Morphogenetic Proteins 4 and 9 (BMP4 and BMP9).
AB  - There is confusion about the role that IFN-alpha plays in the pathogenesis of
      pulmonary arterial hypertension (PAH) with different investigators reporting a
      causative or a protective role. There is now clear evidence in PAH pathogenesis
      for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations
      in BMPR2. In the present study, we investigated MxA, an IFN-alpha-inducible
      cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in
      the presence of PAH-disease-associated mutants of BMPR2. In human pulmonary
      arterial endothelial cells (HPAECs), IFN-alpha-induced endogenous as well as
      exogenously expressed MxA was associated with endosomes that aligned alongside
      microtubules and tubules of the endoplasmic reticulum (ER). Moreover, IFN-alpha
      and MxA stimulated basal and BMP4/9 signaling to a Smad1/5/8-responsive pBRE-Luc
      reporter. In HEK293T cells, immunoelectron microscopy confirmed the association
      of MxA with endosomes, and immunofluorescence methods showed these to be positive
      for early endosome markers (early endosomal antigen 1, clathrin light chain and
      Rab5) and RSmad1/5/8. Functionally, using different genetic and inhibitor
      approaches, we observed that clathrin-mediated endocytosis enhanced and caveolin
      mediated endocytosis inhibited the transcriptional response to BMP4 and BMP9. MxA
      produced a further 3-4-fold enhancement of the BMP-induced response in a clathrin
      endocytosis dependent manner. The microtubule inhibitor nocodazole and stabilizer
      paclitaxel respectively attenuated and enhanced the effect of MxA, implicating
      microtubule integrity in this process. MxA enhanced BMP-induced signaling in the
      presence of wild-type BMPR2, and partially rescued signaling from some PAH
      disease-associated BMPR2 mutants. Taken together, the data identify MxA as a
      novel stimulator of BMP4 and BMP9 transcriptional signaling, and suggest it to be
      a candidate IFN-alpha-inducible mechanism that might have a protective role
      against development of PAH and other vascular diseases.

PMID- 27875557
TI  - Socioeconomic Status and Poor Health Outcome at 10 Years of Follow-Up in the
      Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND/OBJECTIVES: Predictors of healthy aging have not been well-studied
      using longitudinal data with demographic, clinical, subclinical, and genetic
      information. The objective was to identify predictors of poor health outcome at
      10 years of follow-up in the Multi-Ethnic Study of Atherosclerosis (MESA).
      DESIGN: Prospective cohort study. SETTING: Population-based sample from 6 U.S.
      communities. PARTICIPANTS: 4,355 participants In the MESA Study. MEASUREMENTS:
      Poor health outcome at 10 years of follow-up was defined as having died or having
      clinical cardiovascular disease, depression, cognitive impairment, chronic
      obstructive pulmonary disease, or cancer other than non-melanoma skin cancer.
      Absolute risk regression was used to estimate risk differences in the outcome
      adjusting for demographic variables, clinical and behavioral risk factors,
      subclinical cardiovascular disease, and ApoE genotype. Models were weighted to
      account for selective attrition. RESULTS: Mean age at 10 years of follow-up was
      69.5 years; 1,480 participants had a poor health outcome, 2,157 participants were
      in good health, and 718 were unknown. Older age, smoking, not taking a statin,
      hypertension, diabetes, and higher coronary calcium score were associated with
      higher probability of poor health outcome. After multivariable adjustment,
      participants in the lowest income and educational categories had 7 to 14% greater
      absolute risk of poor health outcome at 10 years of follow-up compared to those
      in the next highest categories of income or education (P = 0.002 for both). Those
      in the lowest categories of both income and education had 21% greater absolute
      risk of poor health outcome compared to those in the highest categories of both
      income and education. CONCLUSIONS: Low income and educational level predict poor
      health outcome at 10 years of follow-up in an aging cohort, independent of
      clinical and behavioral risk factors and subclinical cardiovascular disease.

PMID- 27875558
TI  - Palmitoylated APP Forms Dimers, Cleaved by BACE1.
AB  - A major rate-limiting step for Abeta generation and deposition in Alzheimer's
      disease brains is BACE1-mediated cleavage (beta-cleavage) of the amyloid
      precursor protein (APP). We previously reported that APP undergoes palmitoylation
      at two cysteine residues (Cys186 and Cys187) in the E1-ectodomain. 8-10% of total
      APP is palmitoylated in vitro and in vivo. Palmitoylated APP (palAPP) shows
      greater preference for beta-cleavage than total APP in detergent resistant lipid
      rafts. Protein palmitoylation is known to promote protein dimerization. Since
      dimerization of APP at its E1-ectodomain results in elevated BACE1-mediated
      cleavage of APP, we have now investigated whether palmitoylation of APP affects
      its dimerization and whether this leads to elevated beta-cleavage of the protein.
      Here we report that over 90% of palAPP is dimerized while only ~20% of total APP
      forms dimers. PalAPP-dimers are predominantly cis-oriented while total APP
      dimerizes in both cis- and trans-orientation. PalAPP forms dimers 4.5-times more
      efficiently than total APP. Overexpression of the palmitoylating enzymes DHHC7
      and DHHC21 that increase palAPP levels and Abeta release, also increased APP
      dimerization in cells. Conversely, inhibition of APP palmitoylation by
      pharmacological inhibitors reduced APP-dimerization in coimmunoprecipitation and
      FLIM/FRET assays. Finally, in vitro BACE1-activity assays demonstrate that
      palmitoylation-dependent dimerization of APP promotes beta-cleavage of APP in
      lipid-rich detergent resistant cell membranes (DRMs), when compared to total APP.
      Most importantly, generation of sAPPbeta-sAPPbeta dimers is dependent on APP
      palmitoylation while total sAPPbeta generation is not. Since BACE1 shows
      preference for palAPP dimers over total APP, palAPP dimers may serve as novel
      targets for effective beta-cleavage inhibitors of APP as opposed to BACE1
      inhibitors.

PMID- 27875559
TI  - Efficacy and Safety of Anti-Interleukin-5 Therapy in Patients with Asthma: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Recent trials have assessed the efficacy and safety of novel
      monoclonal antibodies such as reslizumab and benralizumab. However, the overall
      efficacy and safety anti-interleukin (IL) 5 treatment in asthma have not been
      thoroughly assessed. METHODS: Randomized controlled trials (RCTs) of anti-IL-5
      treatment on patients with asthma published up to October 2016 in PubMed, Embase,
      and Cochrane Central Register of Controlled Trials (CENTRAL) that reported
      pulmonary function, quality of life scores, asthmatic exacerbation rate, blood
      and sputum eosinophil counts, short-acting beta-agonist (SABA) rescue use, and
      adverse events were included. The pooled mean difference, and relative risks
      (RR), and 95% confidence intervals (CIs) were calculated using random-effects
      models. RESULTS: Twenty studies involving 7100 patients were identified. Pooled
      analysis revealed significant improvements in FEV1 (first second forced
      expiratory volume) (MD = 0.09, 95% CI: 0.06-0.12, I2 = 10%), FEV1% (MD = 3.75,
      95% CI: 1.66-5.83, I2 = 19%), Asthma Quality of Life Questionnaire (AQLQ) score
      (MD = 0.22, 95% CI: 0.15-0.30, I2 = 0%), decreased blood, sputum eosinophils and
      asthmatic exacerbation (RR = 0.66, 95% CI: 0.59-0.73, I2 = 51%); peak expiratory
      flow (PEF) (MD = 5.45, 95% CI: -2.83-13.72, I2 = 0%), histamine PC20 (MD = -0.62,
      95% CI: -1.92-0.68, I2 = 0%) or SABA rescue use (MD = -0.11, 95% CI: -0.3-0.07,
      I2 = 30%) were unaffected; adverse events were not increased (RR = 0.93, 95% CI:
      0.89-0.98, I2 = 46%). No publication bias was observed (Egger's P = 0.78).
      CONCLUSIONS: Anti-interleukin 5 monoclonal therapies for asthma could be safe for
      slightly improving FEV1 (or FEV1% of predicted value), quality of life, and
      reducing exacerbations risk and blood and sputum eosinophils, but have no
      significant effect on PEF, histamine PC20, and SABA rescue use. Further trials
      required to establish to clarify the optimal antibody for different patients.

PMID- 27875561
TI  - The Perception of Physician Empathy by Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND AND AIMS: This study focused on the difference between perceived and
      desired physician empathy (pPE and dPE) in the eye of patients with inflammatory
      bowel disease (IBD). It was investigated if a discrepancy (DeltaPE) correlates
      with trust and satisfaction of patients. At the same time the aim was to gain
      detailed information about the subjective burden of disease and the resources of
      IBD patients, in order to better understand them. METHODS: A modified version of
      the German Version of the Consultation and Relational Empathy (CARE) measure was
      completed as a paper-and-pencil questionnaire by IBD patients attending our
      facility (n = 32) and as an online survey by IBD patients at other locations
      throughout Germany (n = 89). Patients were in average 36.3+/-12 years old.
      RESULTS: The mean (SD) rating of pPE was 3.93 (0.96) on a scale of 1 to 5 ("poor"
      to "excellent"); however, the mean (SD) dPE was 4.38 (0.48) on the same scale.
      DeltaPE correlated with perceived empathy and with patients' satisfaction with
      treatment and trust in their health care providers. Patients reported quite a
      high subjective burden (mean [SD]: 2.93 [.63]) and named family, friends, and
      support groups as resources. CONCLUSIONS: Rather than assessing patient
      satisfaction with treatment and trust in their physician only with perceived PE,
      we suggest DeltaPE as a useful additional parameter.

PMID- 27875560
TI  - Denervation-Induced Activation of the Standard Proteasome and Immunoproteasome.
AB  - The standard 26S proteasome is responsible for the majority of myofibrillar
      protein degradation leading to muscle atrophy. The immunoproteasome is an
      inducible form of the proteasome. While its function has been linked to
      conditions of atrophy, its contribution to muscle proteolysis remains unclear.
      Therefore, the purpose of this study was to determine if the immunoproteasome
      plays a role in skeletal muscle atrophy induced by denervation. Adult male
      C57BL/6 wild type (WT) and immunoproteasome knockout lmp7-/-/mecl-1-/- (L7M1)
      mice underwent tibial nerve transection on the left hindlimb for either 7 or 14
      days, while control mice did not undergo surgery. Proteasome activity (caspase-,
      chymotrypsin-, and trypsin- like), protein content of standard proteasome (beta1,
      beta5 and beta2) and immunoproteasome (LMP2, LMP7 and MECL-1) catalytic subunits
      were determined in the gastrocnemius muscle. Denervation induced significant
      atrophy and was accompanied by increased activities and protein content of the
      catalytic subunits in both WT and L7M1 mice. Although denervation resulted in a
      similar degree of muscle atrophy between strains, the mice lacking two
      immunoproteasome subunits showed a differential response in the extent and
      duration of proteasome features, including activities and content of the beta1,
      beta5 and LMP2 catalytic subunits. The results indicate that immunoproteasome
      deficiency alters the proteasome's composition and activities. However, the
      immunoproteasome does not appear to be essential for muscle atrophy induced by
      denervation.

PMID- 27875562
TI  - Water Quality Is a Poor Predictor of Recreational Hotspots in England.
AB  - Maintaining and improving water quality is key to the protection and restoration
      of aquatic ecosystems, which provide important benefits to society. In Europe,
      the Water Framework Directive (WFD) defines water quality based on a set of
      biological, hydro-morphological and chemical targets, and aims to reach good
      quality conditions in all river bodies by the year 2027. While recently it has
      been argued that achieving these goals will deliver and enhance ecosystem
      services, in particular recreational services, there is little empirical evidence
      demonstrating so. Here we test the hypothesis that good water quality is
      associated with increased utilization of recreational services, combining four
      surveys covering walking, boating, fishing and swimming visits, together with
      water quality data for all water bodies in eight River Basin Districts (RBDs) in
      England. We compared the percentage of visits in areas of good water quality to a
      set of null models accounting for population density, income, age distribution,
      travel distance, public access, and substitutability. We expect such association
      to be positive, at least for fishing (which relies on fish stocks) and swimming
      (with direct contact to water). We also test if these services have stronger
      association with water quality relative to boating and walking alongside rivers,
      canals or lakeshores. In only two of eight RBDs (Northumbria and Anglian) were
      both criteria met (positive association, strongest for fishing and swimming) when
      comparing to at least one of the null models. This conclusion is robust to
      variations in dataset size. Our study suggests that achieving the WFD water
      quality goals may not enhance recreational ecosystem services, and calls for
      further empirical research on the connection between water quality and ecosystem
      services.

PMID- 27875563
TI  - Multimodal Body Representation of Obese Children and Adolescents before and after
      Weight-Loss Treatment in Comparison to Normal-Weight Children.
AB  - OBJECTIVE: The aim of the study was to investigate whether obese children and
      adolescents have a disturbed body representation as compared to normal-weight
      participants matched for age and gender and whether their body representation
      changes in the course of an inpatient weight-reduction program. METHODS: Sixty
      obese (OBE) and 27 normal-weight (NW) children and adolescents (age: 9-17) were
      assessed for body representation using a multi-method approach. Therefore, we
      assessed body size estimation, tactile size estimation, heartbeat detection
      accuracy, and attitudes towards one's own body. OBE were examined upon admission
      and before discharge of an inpatient weight-reduction program. NW served as cross
      sectional control group. RESULTS: Body size estimation and heartbeat detection
      accuracy were similar in OBE and NW. OBE overestimated sizes in tactile size
      estimation and were more dissatisfied with their body as compared to NW. In OBE
      but not in NW, several measures of body size estimation correlated with negative
      body evaluation. After weight-loss treatment, OBE had improved in heartbeat
      detection accuracy and were less dissatisfied with their body. None of the
      assessed variables predicted weight-loss success. CONCLUSIONS: Although OBE
      children and adolescents generally perceived their body size and internal status
      of the body accurately, weight reduction improved their heartbeat detection
      accuracy and body dissatisfaction.

PMID- 27875564
TI  - Donor IFNL4 Genotype Is Associated with Early Post-Transplant Fibrosis in
      Recipients with Hepatitis C.
AB  - BACKGROUND AND AIMS: Early post-transplant hepatic fibrosis is associated with
      poor outcomes and may be influenced by donor/recipient genetic factors. The
      rs368234815 IFNL4 polymorphism is related to the previously described IL28B
      polymorphism, which predicts etiology-independent hepatic fibrosis. The aim of
      this study was to identify the impact of donor and/or recipient IFNL4 genotype on
      early fibrosis among patients transplanted for hepatitis C (HCV). METHODS:
      Clinical data were collected for 302 consecutive patients transplanted for HCV.
      116 patients who had available liver biopsies and donor/recipient DNA were
      included. 28% of these patients with stage 2 fibrosis or greater were compared to
      patients without significant post-transplant fibrosis with respect to clinical
      features as well as donor/recipient IFNL4 genotype. RESULTS: The IFNL4 TT/TT
      genotype was found in 26.0% of recipients and 38.6% of donors. Patients who
      developed early post-transplant fibrosis had a 3.45 adjusted odds of having donor
      IFNL4 TT/TT genotype (p = 0.012). Donor IFNL4 TT/TT genotype also predicted
      decreased overall survival compared to non-TT/TT genotypes (p = 0.016).
      CONCLUSIONS: Donor IFNL4 TT/TT genotype, a favorable predictor of spontaneous HCV
      clearance pre-transplant, is associated with increased early post-transplant
      fibrosis and decreased survival.

PMID- 27875566
TI  - Labor Market Integration of People with Disabilities: Results from the Swiss
      Spinal Cord Injury Cohort Study.
AB  - OBJECTIVES: We aimed to describe labor market participation (LMP) of persons with
      spinal cord injury (SCI) in Switzerland, to examine potential determinants of
      LMP, and to compare LMP between SCI and the general population. METHODS: We
      analyzed data from 1458 participants of employable age from the cross-sectional
      community survey of the Swiss Spinal Cord Injury Cohort Study. Data on LMP of the
      Swiss general population were obtained from the Swiss Federal Statistical Office.
      Factors associated with employment status as well as the amount of work performed
      in terms of full-time equivalent (FTE) were examined with regression techniques.
      RESULTS: 53.4% of the participants were employed at the time of the study.
      Adjusted odds of being employed were increased for males (OR = 1.73, 95% CI 1.33
      2.25) and participants with paraplegia (OR = 1.78, 95% CI 1.40-2.27). The
      likelihood of being employed showed a significant concave relationship with age,
      peaking at age 40. The relation of LMP with education was s-shaped, while LMP was
      linearly related to time since injury. On average, employment rates were 30%
      lower than in the general population. Males with tetraplegia aged between 40 and
      54 showed the greatest difference. From the 771 employed persons, the majority
      (81.7%) worked part-time with a median of 50% FTE (IRQ: 40%-80%). Men, those with
      younger age, higher education, incomplete lesions, and non-traumatic etiology
      showed significantly increased odds of working more hours per week. Significantly
      more people worked part-time than in the general population with the greatest
      difference found for males with tetraplegia aged between 40 and 54. CONCLUSIONS:
      LMP of persons with SCI is comparatively high in Switzerland. LMP after SCI is,
      however, considerably lower than in the general population. Future research needs
      to show whether the reduced LMP in SCI reflects individual capacity adjustment,
      contextual constraints on higher LMP or both.

PMID- 27875565
TI  - Inhibition of Notch Signaling Attenuates Schistosomiasis Hepatic Fibrosis via
      Blocking Macrophage M2 Polarization.
AB  - Macrophages play a key role in the pathogenesis of liver granuloma and fibrosis
      in schistosomiasis. However, the underlying mechanisms have not been fully
      characterized. This study revealed that the macrophages infiltrating the liver
      tissues in a murine model of Schistosoma japonica infection exhibited M2
      functional polarization, and Notch1/Jagged1 signaling was significantly
      upregulated in the M2 polarized macrophages in vivo and in vitro. Furthermore,
      the blockade of Notch signaling pathway by a gamma-secretase inhibitor could
      reverse macrophage M2 polarization in vitro and alleviate liver granuloma and
      fibrosis in the murine model of schistosomiasis. These results implied that the
      Notch1/Jagged1 signaling-dependent M2 polarization of macrophages might play an
      important role in liver granuloma and fibrosis in schistosomiasis, and the
      inhibition of Notch1/Jagged1 signaling might provide a novel therapeutic approach
      to administrate patients with schistosomiasis.

PMID- 27875567
TI  - Transforming Water: Social Influence Moderates Psychological, Physiological, and
      Functional Response to a Placebo Product.
AB  - This paper investigates how social influence can alter physiological,
      psychological, and functional responses to a placebo product and how such
      responses influence the ultimate endorsement of the product. Participants
      consumed a product, "AquaCharge Energy Water," falsely-labeled as containing 200
      mg of caffeine but which was actually plain spring water, in one of three
      conditions: a no social influence condition, a disconfirming social influence
      condition, and a confirming social influence condition. Results demonstrated that
      the effect of the product labeling on physiological alertness (systolic blood
      pressure), psychological alertness (self-reported alertness), functional
      alertness (cognitive interference), and product endorsement was moderated by
      social influence: participants experienced more subjective, physiological and
      functional alertness and stronger product endorsement when they consumed the
      product in the confirming social influence condition than when they consumed the
      product in the disconfirming social influence condition. These results suggest
      that social influence can alter subjective, physiological, and functional
      responses to a faux product, in this case transforming the effects of plain
      water.

PMID- 27875568
TI  - Gated Volumetric-Modulated Arc Therapy vs. Tumor-Tracking CyberKnife Radiotherapy
      as Stereotactic Body Radiotherapy for Hepatocellular Carcinoma: A Dosimetric
      Comparison Study Focused on the Impact of Respiratory Motion Managements.
AB  - PURPOSE: To assess the potential dosimetric benefits associated with the
      CyberKnife (CK) tumor tracking capability, wherein an extra margin for
      respiratory tumor motion is not required, when compared to respiratory-gated
      volumetric-modulated arc therapy (VMAT) for hepatocellular carcinoma (HCC).
      METHODS: Twenty-nine HCC patients previously treated with double-arc VMAT were
      enrolled. In each VMAT plan, the individual internal target volume (ITV) margin
      around the tumor was determined by measuring its motion over 30-70% of
      respiratory phases using four-dimensional computed tomography, followed by a 5-mm
      isotropic margin for the planning target volume (PTV). For each VMAT plan, two CK
      plans were generated using the original (CKoriginal, ITV included) and modified
      PTVs (CKmodified, ITV excluded) for comparison. In each case, the CKoriginal and
      CKmodified plans were compared to the original VMAT plan in terms of the
      dosimetric parameters including the conformity index (CI), PTV coverage (CO),
      organs at risk (OAR) doses, and normal liver tissue sparing. RESULTS: The
      original PTVs with median 24 cc (range, 9-65 cc) were significantly reduced to
      median 12 cc (range, 5-41 cc) in the CKmodified plans. Statistically significant
      differences in plan qualities were observed between the VMAT and the CK plans:
      mean CI, 1.05 in VMAT vs. 1.17 in both CK plans (p < 0.001); and mean CO, 93.0%
      in VMAT vs. 96.6% in CKoriginal and 96.9% in CKmodified (p < 0.001). The average
      volume of normal liver tissue receiving > 15 Gy was significantly decreased in
      the CKmodified plan, as compared to that in the VMAT and CKoriginal plans, by
      1.75- and 1.61-fold, respectively. CONCLUSIONS: The tumor tracking capability of
      the CK system can significantly decrease the volume of normal liver tissue
      receiving > 15 Gy, while maintaining high precision in target localization,
      conformity, tumor coverage, and dose sparing of the OAR. Therefore, it can be a
      valuable SBRT option, particularly for HCC patients with poor liver function.

PMID- 27875569
TI  - Are Men's Perceptions of Sexually Dimorphic Vocal Characteristics Related to
      Their Testosterone Levels?
AB  - Feminine physical characteristics in women are positively correlated with markers
      of their mate quality. Previous research on men's judgments of women's facial
      attractiveness suggests that men show stronger preferences for feminine
      characteristics in women's faces when their own testosterone levels are
      relatively high. Such results could reflect stronger preferences for high quality
      mates when mating motivation is strong and/or following success in male-male
      competition. Given these findings, the current study investigated whether a
      similar effect of testosterone occurs for men's preferences for feminine
      characteristics in women's voices. Men's preferences for feminized versus
      masculinized versions of women's and men's voices were assessed in five weekly
      test sessions and saliva samples were collected in each test session. Analyses
      showed no relationship between men's voice preferences and their testosterone
      levels. Men's tendency to perceive masculinized men's and women's voices as more
      dominant was also unrelated to their testosterone levels. Together, the results
      of the current study suggest that testosterone-linked changes in responses to
      sexually dimorphic characteristics previously reported for men's perceptions of
      faces do not occur for men's perceptions of voices.

PMID- 27875570
TI  - Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac
      Myocytes in the Subpulmonary Circulation.
AB  - The long-term outcome of patients with single ventricles improved over time, but
      remains poor compared to other congenital heart lesions with biventricular
      circulation. Main cause for this unfavourable outcome is the unphysiological
      hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output
      and increased systemic-venous pressure. To overcome this limitation, we are
      developing the concept of a contractile extracardiac Fontan-tunnel. In this
      study, we evaluated the survival and structural development of a tissue
      engineered conduit under in vivo conditions. Engineered heart tissue was
      generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and
      thrombin. Engineered heart tissues started beating around day 8 in vitro and
      remained contractile in vivo throughout the experiment. After culture for 14 days
      constructs were implanted around the right superior vena cava of Wistar rats (n =
      12). Animals were euthanized after 7, 14, 28 and 56 days postoperatively.
      Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles
      within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin,
      alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure.
      Magnetic resonance imaging (d14, n = 3) revealed no constriction or stenosis of
      the superior vena cava by the constructs. Engineered heart tissues survive and
      contract for extended periods after implantation around the superior vena cava of
      rats. Generation of larger constructs is warranted to evaluate functional
      benefits of a contractile Fontan-conduit.

PMID- 27875571
TI  - Short- and Long-Term Mortality Rates of Elderly Acute Kidney Injury Patients Who
      Underwent Continuous Renal Replacement Therapy.
AB  - BACKGROUND: The world's population is aging faster and the incidence of acute
      kidney injury (AKI) needing continuous renal replacement therapy (CRRT) is
      increasing in elderly population. The outcome of AKI needing CRRT in elderly
      patients is known to be poor. However, the definitions of elderly used in the
      previous literatures were diverse and, there were few data that compared the long
      term mortality rates of these patients with middle aged patients. This study was
      aimed to evaluate this issue. METHODS: This study was a single-center,
      retrospective cohort study of patients who underwent CRRT from January 2013 to
      December 2015. The patients were divided into the following four age cohorts:
      middle-aged (55-64), young-old (65-74), middle-old (75-84), and old-old (>=85).
      The short- and long-term mortality rates for each age cohort were compared.
      RESULTS: A total of 562 patients met the inclusion criteria. The short-term
      mortality rate was 57.3% in the entire cohort. Compared with the middle-aged
      cohort, the middle-old cohort (HR 1.48 (1.09-2.02), p = 0.012) and the old-old
      cohort (HR 2.33 (1.30-4.19), p = 0.005) showed an increased short-term mortality
      rate along with an increased SOFA score, acidemia and a prolonged prothrombin
      time. When we analyzed the long-term mortality rate of the 238 survived patients,
      the middle-old cohort (HR 3.76 (1.84-7.68), p<0.001), the old-old cohort (HR
      4.40(1.20-16.10), p = 0.025), a lower BMI, the presence of liver cirrhosis, the
      presence of congestive heart failure and a history of sepsis were independent
      risk factors for the prediction of long-term mortality. CONCLUSION: Compared with
      the middle-aged cohort, the middle-old and the old-old cohort showed an increased
      short-term and long-term mortality rate. However, in the young-old cohort,
      neither the short-term nor the long-term mortality rate was increased.

PMID- 27875572
TI  - Iron-Regulated Phospholipase C Activity Contributes to the Cytolytic Activity and
      Virulence of Acinetobacter baumannii.
AB  - Acinetobacter baumannii is an opportunistic Gram-negative pathogen that causes a
      wide range of infections including pneumonia, septicemia, necrotizing fasciitis
      and severe wound and urinary tract infections. Analysis of A. baumannii
      representative strains grown in Chelex 100-treated medium for hemolytic activity
      demonstrated that this pathogen is increasingly hemolytic to sheep, human and
      horse erythrocytes, which interestingly contain increasing amounts of
      phosphatidylcholine in their membranes. Bioinformatic, genetic and functional
      analyses of 19 A. baumannii isolates showed that the genomes of each strain
      contained two phosphatidylcholine-specific phospholipase C (PC-PLC) genes, which
      were named plc1 and plc2. Accordingly, all of these strains were significantly
      hemolytic to horse erythrocytes and their culture supernatants tested positive
      for PC-PLC activity. Further analyses showed that the transcriptional expression
      of plc1 and plc2 and the production of phospholipase and thus hemolytic activity
      increased when bacteria were cultured under iron-chelation as compared to iron
      rich conditions. Testing of the A. baumannii ATCC 19606T plc1::aph-FRT and
      plc2::aph isogenic insertion derivatives showed that these mutants had a
      significantly reduced PC-PLC activity as compared to the parental strain, while
      testing of plc1::ermAM/plc2::aph demonstrated that this double PC-PLC isogenic
      mutant expressed significantly reduced cytolytic and hemolytic activity.
      Interestingly, only plc1 was shown to contribute significantly to A. baumannii
      virulence using the Galleria mellonella infection model. Taken together, our data
      demonstrate that both PLC1 and PLC2, which have diverged from a common ancestor,
      play a concerted role in hemolytic and cytolytic activities; although PLC1 seems
      to play a more critical role in the virulence of A. baumannii when tested in an
      invertebrate model. These activities would provide access to intracellular iron
      stores this pathogen could use during growth in the infected host.

PMID- 27875573
TI  - A Nucleoside Anticancer Drug, 1-(3-C-Ethynyl-beta-D-Ribo-Pentofuranosyl)Cytosine,
      Induces Depth-Dependent Enhancement of Tumor Cell Death in Spread-Out Bragg Peak
      (SOBP) of Proton Beam.
AB  - The effect of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) on proton
      induced cell death was evaluated in human lung carcinoma cell line A549 and
      Chinese hamster fibroblast cell line V79 to enhance relative biological
      effectiveness (RBE) within the spread-out Bragg peak (SOBP) of proton beams.
      Treatment with ECyd significantly enhanced the proton-induced loss of
      clonogenicity and increased senescence at the center, but not at the distal edge
      of SOBP. The p53-binding protein 1 foci formation assay showed that ECyd
      decelerated the rate of DNA double-strand break (DSB) repair at the center, but
      not the distal region of SOBP, suggesting that the ECyd-induced enhancement of
      proton-induced cell death is partially associated with the inhibition of DSB
      repair. This study demonstrated that ECyd enhances proton-induced cell killing at
      all positions of SOBP, except for the distal region and minimizes the site
      dependent differences in RBE within SOBP. Thus, ECyd is a unique radiosensitizer
      for proton therapy that may be useful because it levels the biological dose
      within SOBP, which improves tumor control and reduces the risk of adverse effects
      at the distal edge of SOBP.

PMID- 27875574
TI  - Chidamide Inhibits Aerobic Metabolism to Induce Pancreatic Cancer Cell Growth
      Arrest by Promoting Mcl-1 Degradation.
AB  - Pancreatic cancer is a fatal malignancy worldwide and urgently requires valid
      therapies. Previous research showed that the HDAC inhibitor chidamide is a
      promising anti-cancer agent in pancreatic cancer cell lines. In this study, we
      elucidate a probable underlying anti-cancer mechanism of chidamide involving the
      degradation of Mcl-1. Mcl-1 is frequently upregulated in human cancers, which has
      been demonstrated to participate in oxidative phosphorylation, in addition to its
      anti-apoptotic actions as a Bcl-2 family member. The pancreatic cancer cell lines
      BxPC-3 and PANC-1 were treated with chidamide, resulting in Mcl-1 degradation
      accompanied by induction of Mcl-1 ubiquitination. Treatment with MG132, a
      proteasome inhibitor reduced Mcl-1 degradation stimulated by chidamide. Chidamide
      decreased O2 consumption and ATP production to inhibit aerobic metabolism in both
      pancreatic cancer cell lines and primary cells, similar to knockdown of Mcl-1,
      while overexpression of Mcl-1 in pancreatic cancer cells could restore the
      aerobic metabolism inhibited by chidamide. Furthermore, chidamide treatment or
      Mcl-1 knockdown significantly induced cell growth arrest in pancreatic cancer
      cell lines and primary cells, and Mcl-1 overexpression could reduce this cell
      growth inhibition. In conclusion, our results suggest that chidamide promotes Mcl
      1 degradation through the ubiquitin-proteasome pathway, suppressing the
      maintenance of mitochondrial aerobic respiration by Mcl-1, and resulting in
      inhibition of pancreatic cancer cell proliferation. Our work supports the claim
      that chidamide has therapeutic potential for pancreatic cancer treatment.

PMID- 27875575
TI  - Auditory Time-Frequency Masking for Spectrally and Temporally Maximally-Compact
      Stimuli.
AB  - Many audio applications perform perception-based time-frequency (TF) analysis by
      decomposing sounds into a set of functions with good TF localization (i.e. with a
      small essential support in the TF domain) using TF transforms and applying
      psychoacoustic models of auditory masking to the transform coefficients. To
      accurately predict masking interactions between coefficients, the TF properties
      of the model should match those of the transform. This involves having masking
      data for stimuli with good TF localization. However, little is known about TF
      masking for mathematically well-localized signals. Most existing masking studies
      used stimuli that are broad in time and/or frequency and few studies involved TF
      conditions. Consequently, the present study had two goals. The first was to
      collect TF masking data for well-localized stimuli in humans. Masker and target
      were 10-ms Gaussian-shaped sinusoids with a bandwidth of approximately one
      critical band. The overall pattern of results is qualitatively similar to
      existing data for long maskers. To facilitate implementation in audio processing
      algorithms, a dataset provides the measured TF masking function. The second goal
      was to assess the potential effect of auditory efferents on TF masking using a
      modeling approach. The temporal window model of masking was used to predict
      present and existing data in two configurations: (1) with standard model
      parameters (i.e. without efferents), (2) with cochlear gain reduction to simulate
      the activation of efferents. The ability of the model to predict the present data
      was quite good with the standard configuration but highly degraded with gain
      reduction. Conversely, the ability of the model to predict existing data for long
      maskers was better with than without gain reduction. Overall, the model
      predictions suggest that TF masking can be affected by efferent (or other)
      effects that reduce cochlear gain. Such effects were avoided in the experiment of
      this study by using maximally-compact stimuli.

PMID- 27875576
TI  - Small RNA Library Preparation Method for Next-Generation Sequencing Using
      Chemical Modifications to Prevent Adapter Dimer Formation.
AB  - For most sample types, the automation of RNA and DNA sample preparation workflows
      enables high throughput next-generation sequencing (NGS) library preparation.
      Greater adoption of small RNA (sRNA) sequencing has been hindered by high sample
      input requirements and inherent ligation side products formed during library
      preparation. These side products, known as adapter dimer, are very similar in
      size to the tagged library. Most sRNA library preparation strategies thus employ
      a gel purification step to isolate tagged library from adapter dimer
      contaminants. At very low sample inputs, adapter dimer side products dominate the
      reaction and limit the sensitivity of this technique. Here we address the need
      for improved specificity of sRNA library preparation workflows with a novel
      library preparation approach that uses modified adapters to suppress adapter
      dimer formation. This workflow allows for lower sample inputs and elimination of
      the gel purification step, which in turn allows for an automatable sRNA library
      preparation protocol.

PMID- 27875577
TI  - Heat Stress Affects Facultative Symbiont-Mediated Protection from a Parasitoid
      Wasp.
AB  - Many insects carry facultative bacterial symbionts, which provide benefits
      including resistance to natural enemies and abiotic stresses. Little is known
      about how these beneficial phenotypes are affected when biotic or abiotic threats
      occur simultaneously. The pea aphid (Acyrthosiphon pisum) can host several well
      characterized symbiont species. The symbiont known as X-type can protect against
      both parasitoid wasps and heat stress. Here, we used three pea aphid genotypes
      that were naturally infected with X-type and the symbiont Spiroplasma sp. We
      compared aphids coinfected with these two symbionts with those cured from X-type
      and infected with only Spiroplasma to investigate the ability of X-type to confer
      benefits to the host when two threats are experienced simultaneously. Our aim is
      to explore how robust symbiont protection may be outside a benign laboratory
      environment. Aphids were subjected to heat shock either before or after attack by
      parasitoid wasps. Under a benign temperature regime, the aphids carrying X-type
      tended to be better protected from the parasitoid than those cured. When the
      aphids experienced a heat shock before being parasitized aphids carrying X-type
      were more susceptible than those cured. Regardless of infection with the
      symbiont, the aphids benefitted from being heat shocked after parasitization. The
      results demonstrate how resistance to parasitoid wasps can be strongly
      environment-dependent and that a beneficial phenotype conferred by a symbiont
      under controlled conditions in the laboratory does not necessarily equate to a
      consistently useful effect in natural populations.

PMID- 27875578
TI  - Transcriptome Analysis of the Chrysanthemum Foliar Nematode, Aphelenchoides
      ritzemabosi (Aphelenchida: Aphelenchoididae).
AB  - The chrysanthemum foliar nematode (CFN), Aphelenchoides ritzemabosi, is a plant
      parasitic nematode that attacks many plants. In this study, a transcriptomes of
      mixed-stage population of CFN was sequenced on the Illumina HiSeq 2000 platform.
      68.10 million Illumina high quality paired end reads were obtained which
      generated 26,817 transcripts with a mean length of 1,032 bp and an N50 of 1,672
      bp, of which 16,467 transcripts were annotated against six databases. In total,
      20,311 coding region sequences (CDS), 495 simple sequence repeats (SSRs) and
      8,353 single-nucleotide polymorphisms (SNPs) were predicted, respectively. The
      CFN with the most shared sequences was B. xylophilus with 16,846 (62.82%) common
      transcripts and 10,543 (39.31%) CFN transcripts matched sequences of all of four
      plant parasitic nematodes compared. A total of 111 CFN transcripts were predicted
      as homologues of 7 types of carbohydrate-active enzymes (CAZymes) with
      plant/fungal cell wall-degrading activities, fewer transcripts were predicted as
      homologues of plant cell wall-degrading enzymes than fungal cell wall-degrading
      enzymes. The phylogenetic analysis of GH5, GH16, GH43 and GH45 proteins between
      CFN and other organisms showed CFN and other nematodes have a closer phylogenetic
      relationship. In the CFN transcriptome, sixteen types of genes orthologues with
      seven classes of protein families involved in the RNAi pathway in C. elegans were
      predicted. This research provides comprehensive gene expression information at
      the transcriptional level, which will facilitate the elucidation of the molecular
      mechanisms of CFN and the distribution of gene functions at the macro level,
      potentially revealing improved methods for controlling CFN.

PMID- 27875579
TI  - Wealth and Disability in Later Life: The English Longitudinal Study of Ageing
      (ELSA).
AB  - We examined wealth inequalities in disability, taking into account the effect of
      both depression and social support among older English adults using data from
      5,506 community-dwelling people aged 50 years and over from the English
      Longitudinal Study of Ageing (ELSA). Disability was measured as self-reported
      limitations in the Basic Activities of Daily Living (ADL) and Instrumental
      Activities of Daily Living (IADL). Depressive symptomatology was measured using
      the 8-item Center for Epidemiological Studies-Depression (CES-D) scale. Social
      support was assessed by marital status and frequency of contact with friends,
      relatives or children. Multinomial logistic regression models were used to assess
      the role of social support and depressive symptoms on disability by total
      household wealth, which is a measure of accumulated assets over the course of
      life. Our findings showed that the poorest men with disability were more likely
      to live without a partner and have no weekly contact with children, family or
      friends compared to the wealthiest. Among women with disability, the poorest were
      more likely to report loneliness and have no partner while the wealthiest and the
      intermediate groups were more likely to be living with a partner. There was a
      strong inverse dose-response association between wealth and depressive symptoms
      among all participants with disability. This study shows a clear wealth gradient
      in disability among older English adults, especially for those with elevated
      depressive symptoms.

PMID- 27875580
TI  - Inescapable Stress Changes Walking Behavior in Flies - Learned Helplessness
      Revisited.
AB  - Like other animals flies develop a state of learned helplessness in response to
      unescapable aversive events. To show this, two flies, one 'master', one 'yoked',
      are each confined to a dark, small chamber and exposed to the same sequence of
      mild electric shocks. Both receive these shocks when the master fly stops walking
      for more than a second. Behavior in the two animals is differently affected by
      the shocks. Yoked flies are transiently impaired in place learning and take
      longer than master flies to exit from the chamber towards light. After the
      treatment they walk more slowly and take fewer and shorter walking bouts. The low
      activity is attributed to the fly's experience that its escape response, an
      innate behavior to terminate the electric shocks, does not help anymore. Earlier
      studies using heat pulses instead of electric shocks had shown similar effects.
      This parallel supports the interpretation that it is the uncontrollability that
      induces the state.

PMID- 27875581
TI  - Statistical Models for Tornado Climatology: Long and Short-Term Views.
AB  - This paper estimates regional tornado risk from records of past events using
      statistical models. First, a spatial model is fit to the tornado counts
      aggregated in counties with terms that control for changes in observational
      practices over time. Results provide a long-term view of risk that delineates the
      main tornado corridors in the United States where the expected annual rate
      exceeds two tornadoes per 10,000 square km. A few counties in the Texas Panhandle
      and central Kansas have annual rates that exceed four tornadoes per 10,000 square
      km. Refitting the model after removing the least damaging tornadoes from the data
      (EF0) produces a similar map but with the greatest tornado risk shifted south and
      eastward. Second, a space-time model is fit to the counts aggregated in raster
      cells with terms that control for changes in climate factors. Results provide a
      short-term view of risk. The short-term view identifies a shift of tornado
      activity away from the Ohio Valley under El Nino conditions and away from the
      Southeast under positive North Atlantic oscillation conditions. The combined
      predictor effects on the local rates is quantified by fitting the model after
      leaving out the year to be predicted from the data. The models provide state-of
      the-art views of tornado risk that can be used by government agencies, the
      insurance industry, and the general public.

PMID- 27875582
TI  - Changes in Intracellular Na+ following Enhancement of Late Na+ Current in Virtual
      Human Ventricular Myocytes.
AB  - The slowly inactivating or late Na+ current, INa-L, can contribute to the
      initiation of both atrial and ventricular rhythm disturbances in the human heart.
      However, the cellular and molecular mechanisms that underlie these pro-arrhythmic
      influences are not fully understood. At present, the major working hypothesis is
      that the Na+ influx corresponding to INa-L significantly increases intracellular
      Na+, [Na+]i; and the resulting reduction in the electrochemical driving force for
      Na+ reduces and (may reverse) Na+/Ca2+ exchange. These changes increase
      intracellular Ca2+, [Ca2+]i; which may further enhance INa-L due to calmodulin
      dependent phosphorylation of the Na+ channels. This paper is based on
      mathematical simulations using the O'Hara et al (2011) model of baseline or
      healthy human ventricular action potential waveforms(s) and its [Ca2+]i
      homeostasis mechanisms. Somewhat surprisingly, our results reveal only very small
      changes (<= 1.5 mM) in [Na+]i even when INa-L is increased 5-fold and steady
      state stimulation rate is approximately 2 times the normal human heart rate (i.e.
      2 Hz). Previous work done using well-established models of the rabbit and human
      ventricular action potential in heart failure settings also reported little or no
      change in [Na+]i when INa-L was increased. Based on our simulations, the major
      short-term effect of markedly augmenting INa-L is a significant prolongation of
      the action potential and an associated increase in the likelihood of reactivation
      of the L-type Ca2+ current, ICa-L. Furthermore, this action potential
      prolongation does not contribute to [Na+]i increase.

PMID- 27875584
TI  - Correction: Population Genetic Structure of Apple Scab (Venturia inaequalis
      (Cooke) G. Winter) in Iran.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0160737.].

PMID- 27875585
TI  - Correction: Benefits of a Working Memory Training Program for Inattention in
      Daily Life: A Systematic Review and Meta-Analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0119522.].

PMID- 27875583
TI  - K63-Linked Ubiquitination Targets Toxoplasma gondii for Endo-lysosomal
      Destruction in IFNgamma-Stimulated Human Cells.
AB  - Toxoplasma gondii is the most common protozoan parasitic infection in man. Gamma
      interferon (IFNgamma) activates haematopoietic and non-haematopoietic cells to
      kill the parasite and mediate host resistance. IFNgamma-driven host resistance
      pathways and parasitic virulence factors are well described in mice, but a
      detailed understanding of pathways that kill Toxoplasma in human cells is
      lacking. Here we show, that contrary to the widely held belief that the
      Toxoplasma vacuole is non-fusogenic, in an immune-stimulated environment, the
      vacuole of type II Toxoplasma in human cells is able to fuse with the host endo
      lysosomal machinery leading to parasite death by acidification. Similar to murine
      cells, we find that type II, but not type I Toxoplasma vacuoles are targeted by
      K63-linked ubiquitin in an IFNgamma-dependent manner in non-haematopoetic primary
      like human endothelial cells. Host defence proteins p62 and NDP52 are
      subsequently recruited to the type II vacuole in distinct, overlapping
      microdomains with a loss of IFNgamma-dependent restriction in p62 knocked down
      cells. Autophagy proteins Atg16L1, GABARAP and LC3B are recruited to <10% of
      parasite vacuoles and show no parasite strain preference, which is consistent
      with inhibition and enhancement of autophagy showing no effect on parasite
      replication. We demonstrate that this differs from HeLa human epithelial cells,
      where type II Toxoplasma are restricted by non-canonical autophagy leading to
      growth stunting that is independent of lysosomal acidification. In contrast to
      mouse cells, human vacuoles do not break. In HUVEC, the ubiquitinated vacuoles
      are targeted for destruction in acidified LAMP1-positive endo-lysosomal
      compartments. Consequently, parasite death can be prevented by inhibiting host
      ubiquitination and endosomal acidification. Thus, K63-linked ubiquitin
      recognition leading to vacuolar endo-lysosomal fusion and acidification is an
      important, novel virulence-driven Toxoplasma human host defence pathway.

PMID- 27875587
TI  - Correction: Loading-Induced Heat-Shock Response in Bovine Intervertebral Disc
      Organ Culture.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0161615.].

PMID- 27875586
TI  - Correction: Disruption of FGF5 in Cashmere Goats Using CRISPR/Cas9 Results in
      More Secondary Hair Follicles and Longer Fibers.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0164640.].

PMID- 27875588
TI  - Genetic Diversity of Blumeria graminis f. sp. hordei in Central Europe and Its
      Comparison with Australian Population.
AB  - Population surveys of Blumeria graminis f. sp. hordei (Bgh), a causal agent of
      more than 50% of barley fungal infections in the Czech Republic, have been
      traditionally based on virulence tests, at times supplemented with non-specific
      Restriction fragment length polymorphism or Random amplified polymorphic DNA
      markers. A genomic sequence of Bgh, which has become available recently, enables
      identification of potential markers suitable for population genetics studies. Two
      major strategies relying on transposable elements and microsatellites were
      employed in this work to develop a set of Repeat junction markers, Single
      sequence repeat and Single nucleotide polymorphism markers. A resolution power of
      the new panel of markers comprising 33 polymorphisms was demonstrated by a
      phylogenetic analysis of 158 Bgh isolates. A core set of 97 Czech isolates was
      compared to a set 50 Australian isolates on the background of 11 diverse isolates
      collected throughout the world. 73.2% of Czech isolates were found to be
      genetically unique. An extreme diversity of this collection was in strong
      contrast with the uniformity of the Australian one. This work paves the way for
      studies of population structure and dynamics based on genetic variability among
      different Bgh isolates originating from geographically limited regions.

PMID- 27875589
TI  - On the Effects of Artificial Feeding on Bee Colony Dynamics: A Mathematical
      Model.
AB  - This paper proposes a new mathematical model to evaluate the effects of
      artificial feeding on bee colony population dynamics. The proposed model is based
      on a classical framework and contains differential equations that describe the
      changes in the number of hive bees, forager bees, and brood cells, as a function
      of amounts of natural and artificial food. The model includes the following
      elements to characterize the artificial feeding scenario: a function to model the
      preference of the bees for natural food over artificial food; parameters to
      quantify the quality and palatability of artificial diets; a function to account
      for the efficiency of the foragers in gathering food under different
      environmental conditions; and a function to represent different approaches used
      by the beekeeper to feed the hive with artificial food. Simulated results are
      presented to illustrate the main characteristics of the model and its behavior
      under different scenarios. The model results are validated with experimental data
      from the literature involving four different artificial diets. A good match
      between simulated and experimental results was achieved.

PMID- 27875590
TI  - Spatio-Temporal Progression of Cortical Activity Related to Continuous Overt and
      Covert Speech Production in a Reading Task.
AB  - How the human brain plans, executes, and monitors continuous and fluent speech
      has remained largely elusive. For example, previous research has defined the
      cortical locations most important for different aspects of speech function, but
      has not yet yielded a definition of the temporal progression of involvement of
      those locations as speech progresses either overtly or covertly. In this paper,
      we uncovered the spatio-temporal evolution of neuronal population-level activity
      related to continuous overt speech, and identified those locations that shared
      activity characteristics across overt and covert speech. Specifically, we asked
      subjects to repeat continuous sentences aloud or silently while we recorded
      electrical signals directly from the surface of the brain (electrocorticography
      (ECoG)). We then determined the relationship between cortical activity and speech
      output across different areas of cortex and at sub-second timescales. The results
      highlight a spatio-temporal progression of cortical involvement in the continuous
      speech process that initiates utterances in frontal-motor areas and ends with the
      monitoring of auditory feedback in superior temporal gyrus. Direct comparison of
      cortical activity related to overt versus covert conditions revealed a common
      network of brain regions involved in speech that may implement orthographic and
      phonological processing. Our results provide one of the first characterizations
      of the spatiotemporal electrophysiological representations of the continuous
      speech process, and also highlight the common neural substrate of overt and
      covert speech. These results thereby contribute to a refined understanding of
      speech functions in the human brain.

PMID- 27875591
TI  - Reentry and Ectopic Pacemakers Emerge in a Three-Dimensional Model for a Slab of
      Cardiac Tissue with Diffuse Microfibrosis near the Percolation Threshold.
AB  - Arrhythmias in cardiac tissue are generally associated with irregular electrical
      wave propagation in the heart. Cardiac tissue is formed by a discrete cell
      network, which is often heterogeneous. Recently, it was shown in simulations of
      two-dimensional (2D) discrete models of cardiac tissue that a wave crossing a
      fibrotic, heterogeneous region may produce reentry and transient or persistent
      ectopic activity provided the fraction of conducting connections is just above
      the percolation threshold. Here, we investigate the occurrence of these phenomena
      in three-dimensions by simulations of a discrete model representing a thin slab
      of cardiac tissue. This is motivated (i) by the necessity to study the relevance
      and properties of the percolation-related mechanism for the emergence of
      microreentries in three dimensions and (ii) by the fact that atrial tissue is
      quite thin in comparison with ventricular tissue. Here, we simplify the model by
      neglecting details of tissue anatomy, e. g. geometries of atria or ventricles and
      the anisotropy in the conductivity. Hence, our modeling study is confined to the
      investigation of the effect of the tissue thickness as well as to the comparison
      of the dynamics of electrical excitation in a 2D layer with the one in a 3D slab.
      Our results indicate a strong and non-trivial effect of the thickness even for
      thin tissue slabs on the probability of microreentries and ectopic beat
      generation. The strong correlation of the occurrence of microreentry with the
      percolation threshold reported earlier in 2D layers persists in 3D slabs.
      Finally, a qualitative agreement of 3D simulated electrograms in the fibrotic
      region with the experimentally observed complex fractional atrial electrograms
      (CFAE) as well as strong difference between simulated electrograms in 2D and 3D
      were found for the cases where reentry and ectopic activity were triggered by the
      micro-fibrotic region.

PMID- 27875592
TI  - Curcumin Generates Oxidative Stress and Induces Apoptosis in Adult Schistosoma
      mansoni Worms.
AB  - Inducing apoptosis is an interesting therapeutic approach to develop drugs that
      act against helminthic parasites. Researchers have investigated how curcumin
      (CUR), a biologically active compound extracted from rhizomes of Curcuma longa,
      affects Schistosoma mansoni and several cancer cell lines. This study evaluates
      how CUR influences the induction of apoptosis and oxidative stress in couples of
      adult S. mansoni worms. CUR decreased the viability of adult worms and killed
      them. The tegument of the parasite suffered morphological changes, the
      mitochondria underwent alterations, and chromatin condensed. Different apoptotic
      parameters were determined in an attempt to understand how CUR affected adult S.
      mansoni worms. CUR induced DNA damage and fragmentation and increased the
      expression of SmCASP3/7 transcripts and the activity of Caspase 3 in female and
      male worms. However, CUR did not intensify the activity of Caspase 8 in female or
      male worms. Evaluation of the superoxide anion and different antioxidant enzymes
      helped to explore the mechanism of parasite death further. The level of
      superoxide anion and the activity of Superoxide Dismutase (SOD) increased,
      whereas the activity of Glutathione-S-Transferase (GST), Glutathione reductase
      (GR), and Glutathione peroxidase (GPX) decreased, which culminated in the
      oxidation of proteins in adult female and male worms incubated with CUR. In
      conclusion, CUR generated oxidative stress followed by apoptotic-like-events in
      both adult female and male S. mansoni worms, ultimately killing them.

PMID- 27875593
TI  - Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and
      Clinical Outcomes.
AB  - BACKGROUND: An outbreak of enterovirus D68 (EV-D68) caused severe respiratory
      illness in 2014. The disease spectrum of EV-D68 infections in children with
      underlying medical conditions other than asthma, the role of EV-D68 loads on
      clinical illness, and the variation of EV-D68 strains within the same institution
      over time have not been described. We sought to define the association between EV
      D68 loads and sequence variation, and the clinical characteristic in hospitalized
      children at our institution from 2011 to 2014. METHODS: May through November
      2014, and August to September 2011 to 2013, a convenience sample of
      nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory
      infections were tested for EV-D68 by RT-PCR. Clinical data were compared between
      children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV
      D68 infections categorized as healthy, asthmatics, and chronic medical
      conditions. EV-D68 loads were analyzed in relation to disease severity parameters
      and sequence variability characterized over time. RESULTS: In 2014, 44% (192/438)
      of samples tested positive for EV-D68 vs. 10% (13/130) in 2011-13 (p<0.0001).
      PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more
      common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+
      children, required supplemental oxygen administration (p = 0.03) and PICU
      admissions (p <0.001) more frequently than healthy children or those with chronic
      medical conditions; however oxygen duration (p<0.0001), and both PICU and total
      hospital stay (p<0.01) were greater in children with underlying medical
      conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV
      D68 strains clustered into a new sublineage within clade B. CONCLUSIONS: This is
      one of the largest pediatric cohorts described from the EV-D68 outbreak.
      Irrespective of viral loads, EV-D68 was associated with high morbidity in
      children with asthma and co-morbidities. While EV-D68 circulated before 2014, the
      outbreak isolates clustered differently than those from prior years.

PMID- 27875594
TI  - Seroprevalence of Antibodies against Plasmodium falciparum Sporozoite Antigens as
      Predictive Disease Transmission Markers in an Area of Ghana with Seasonal Malaria
      Transmission.
AB  - INTRODUCTION: As an increasing number of malaria-endemic countries approach the
      disease elimination phase, sustenance of control efforts and effective monitoring
      are necessary to ensure success. Mathematical models that estimate anti-parasite
      antibody seroconversion rates are gaining relevance as more sensitive
      transmission intensity estimation tools. Models however estimate yearly
      seroconversion and seroreversion rates and usually predict long term changes in
      transmission, occurring years before the time of sampling. Another challenge is
      the identification of appropriate antigen targets since specific antibody levels
      must directly reflect changes in transmission patterns. We therefore investigated
      the potential of antibodies to sporozoite and blood stage antigens for detecting
      short term differences in malaria transmission in two communities in Northern
      Ghana with marked, seasonal transmission. METHODS: Cross-sectional surveys were
      conducted during the rainy and dry seasons in two communities, one in close
      proximity to an irrigation dam and the other at least 20 Km away from the dam.
      Antibodies against the sporozoite-specific antigens circumsporozoite protein
      (CSP) and Cell traversal for ookinetes and sporozoites (CelTOS) and the classical
      blood stage antigen apical membrane antigen 1 (AMA1) were measured by indirect
      ELISA. Antibody levels and seroprevalence were compared between surveys and
      between study communities. Antibody seroprevalence data were fitted to a modified
      reversible catalytic model to estimate the seroconversion and seroreversion
      rates. RESULTS: Changes in sporozoite-specific antibody levels and seroprevalence
      directly reflected differences in parasite prevalence between the rainy and dry
      seasons and hence the extent of malaria transmission. Seroconversion rate
      estimates from modelled seroprevalence data did not however support the above
      observation. CONCLUSIONS: The data confirms the potential utility of sporozoite
      specific antigens as useful markers for monitoring short term/seasonal changes in
      malaria transmission. It may however be essential to update models to allow for
      assessment of seasonal changes in malaria transmission, which usually occur
      within four to six months.

PMID- 27875595
TI  - Phosphorylation of Serine 235 of the Hepatitis C Virus Non-Structural Protein
      NS5A by Multiple Kinases.
AB  - Phosphorylation at serine 235 (S235) of the hepatitis C virus (HCV) non
      structural protein 5A (NS5A) plays a critical role in the viral life cycle. For
      medical and virological interests, we exploited the HEK293T kidney cells to test
      3 candidate protein kinases on NS5A S235 phosphorylation. Inhibitors that inhibit
      casein kinase I alpha (CKIalpha), polo-like kinase I (PlKI) or calmodulin
      dependent kinase II (CaMKII) all reduced NS5A S235 phosphorylation. CKIalpha was
      studied previously and PlKI had severe cytotoxicity, thus CaMKII was selected for
      validation in the Huh7.5.1 liver cells. In the HCV (J6/JFH1)-infected Huh7.5.1
      cells, CaMKII inhibitor reduced NS5A S235 phosphorylation and HCV RNA levels
      without apparent cytotoxicity. RT-PCR analysis showed expression of CaMKII gamma
      and delta isoforms in the Huh7.5.1 cells. Both CaMKII gamma and delta directly
      phosphorylated NS5A S235 in vitro. CaMKII gamma or delta single knockdown did not
      affect NS5A S235 phosphorylation but elevated the HCV RNA levels in the infected
      cells. CKIalpha plus CaMKII (gamma or delta) double knockdown reduced NS5A S235
      phosphorylation and reduced HCV RNA levels; however, the HCV RNA levels were
      higher than those in the infected cells with CKIalpha single knockdown. We
      conclude that CKIalpha-mediated NS5A S235 phosphorylation is critical for HCV
      replication. CaMKII gamma and delta may have negative roles in the HCV life
      cycle.

PMID- 27875597
TI  - Family Medicine and the Social Mission of Medical Education.

PMID- 27875598
TI  - Results of the 2016 National Resident Matching Program(r): 1986-2016: A
      Comparison of Family Medicine, E-ROADs, and Other Select Specialties.
AB  - BACKGROUND AND OBJECTIVES: This article is a continuation in a series of national
      studies conducted by the American Academy of Family Physicians that reports the
      performance of family medicine and other primary care specialties in the National
      Residency Matching Program(r) (NRMP) Main Residency Match, hereafter called the
      Match. Match data from 1986-2016 were analyzed to compare the numbers of
      positions offered and filled in family medicine, other primary care specialties,
      emergency medicine, diagnostic radiology, ophthalmology, anesthesiology, and
      dermatology (E-ROAD), and other select specialties. Of the 10 largest specialties
      defined by the greatest number of positions offered in the 2016 Match, all but
      one (general surgery) have experienced growth since 1986.Overall, the total
      number of positions offered in the Match grew by an average of 226 positions per
      year. At the same time, primary care specialties grew 19 positions per year, and
      E-ROAD specialties grew by 72 positions per year. The disproportionate growth of
      subspecialties overall, notably the E-ROAD subspecialties, relative to the modest
      growth of primary care specialties, makes the goal of better health care harder
      to achieve. The GME portion of physician workforce pipeline is mismatched to the
      health needs of the nation, and this mismatch is worsening.

PMID- 27875599
TI  - Differences in Canadian and US Medical Student Preparation for Family Medicine.

PMID- 27875596
TI  - Cost-Effectiveness of Saxagliptin versus Acarbose as Second-Line Therapy in Type
      2 Diabetes in China.
AB  - OBJECTIVE: This study assessed the long-term cost-effectiveness of
      saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese
      patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET
      alone. METHODS: Systematic literature reviews were performed to identify studies
      directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related
      events costs which were modified by hospital surveys. A Cardiff Diabetes Model
      was used to estimate the long-term economic and health treatment consequences in
      patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer's
      perspective and estimated over a patient's lifetime. RESULTS: SAXA+MET predicted
      lower incidences of most cardiovascular events, hypoglycemia events and fatal
      events, and decreased total costs compared with ACAR+MET. For an individual
      patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48
      more than ACAR+MET at a cost saving of Y18,736, which resulted in a cost saving
      of Y38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust
      across various univariate and probabilistic sensitivity analyses. CONCLUSION:
      SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for
      patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an
      effective, well-tolerated drug with a low incidence of adverse events and ease of
      administration; it is anticipated to be an effective second-line therapy for T2DM
      treatment.

PMID- 27875600
TI  - Finding the Words: Medical Students' Reflections on Communication Challenges in
      Clinic.
AB  - BACKGROUND AND OBJECTIVES: Interpersonal communication is essential to providing
      excellent patient care and requires ongoing development. Although aspects of
      medical student interpersonal communication may degrade throughout career
      progression, it is unknown what specific elements pose challenges. We aimed to
      characterize clerkship students' perspectives on communication challenges in the
      outpatient setting to help inform curricular development. METHODS: Third-year
      medical students in a required family medicine clerkship were asked to describe a
      communication challenge they encountered. Open-ended written responses were
      collected through a mandatory post-clerkship survey. Responses were qualitatively
      coded using an a priori framework for teaching and assessing communication skills
      (The SEGUE Framework for Teaching and Assessing Communication Skills) with data
      derived additions to the framework, followed by a team-based thematic analysis.
      RESULTS: We collected 799 reflections written by 518 students from 2007-2014.
      Three dominant themes emerged from the analysis: challenges with (1) effectively
      exchanging information with patients, (2) managing emotional aspects of the
      patient encounter, and (3) negotiating terms of the encounter. CONCLUSIONS:
      Communication curricula focus on content and process of the medical interview,
      but insufficient time and energy are devoted to psychosocial factors, including
      aspects of the encounter that are emotionally charged or conflicting. While gaps
      in students' communication skillsets may be anticipated or observed by educators,
      this study offers an analysis of students' own perceptions of the challenges they
      face.

PMID- 27875602
TI  - Practice Facilitation for PCMH Implementation in Residency Practices.
AB  - BACKGROUND AND OBJECTIVES: Primary care residency programs continue to adapt and
      change to become high-performing training sites for advanced primary care.
      Practice facilitation is a key method to assist practices in implementing
      organizational changes. This evaluation described the unique nature and essential
      roles and qualities of practice facilitation for residency program patient
      centered medical home (PCMH) transformation. METHODS: Evaluation of the Colorado
      Residency PCMH Project from 2009 through 2014 included template and immersion
      crystallization approaches to qualitative analysis of field notes, key informant
      interviews, and meeting documentation to identify themes related to external
      facilitation for practice transformation in 11 Colorado primary care residency
      practices. RESULTS: Important practice facilitator roles in residency practice
      transformation included supporter of quality improvement and NCQA implementation,
      connector of practices, and leadership and engagement coach. Key qualities
      included the relationship development between practice members and facilitators
      over time, flexibility, consistent presence and communication, and an external
      nature that provided a valuable outside perspective. CONCLUSIONS: Residency
      programs provide a unique environment that is particularly well-suited for
      transformation, though it also presents challenges. External practice
      facilitators that demonstrate key roles and qualities can support residency
      practices through this complex transformation process.

PMID- 27875601
TI  - Association Between Patient- Centered Medical Home Features and Satisfaction With
      Family Medicine Residency Training in the US.
AB  - BACKGROUND AND OBJECTIVES: Primary care residencies are undergoing dramatic
      changes because of changing health care systems and evolving demands for updated
      training models. We examined the relationships between residents' exposures to
      patient-centered medical home (PCMH) features in their assigned continuity
      clinics and their satisfaction with training. METHODS: Longitudinal surveys were
      collected annually from residents evaluating satisfaction with training using a 5
      point Likert-type scale (1=very unsatisfied to 5=very satisfied) from 2007
      through 2011, and the presence or absence of PCMH features were collected from 24
      continuity clinics during the same time period. Odds ratios on residents' overall
      satisfaction were compared according to whether they had no exposure to PCMH
      features, some exposure (1-2 years), or full exposure (all 3 or more years).
      RESULTS: Fourteen programs and 690 unique residents provided data to this study.
      Resident satisfaction with training was highest with full exposure for integrated
      case management compared to no exposure, which occurred in 2010 (OR=2.85, 95%
      CI=1.40, 5.80). Resident satisfaction was consistently statistically lower with
      any or full exposure (versus none) to expanded clinic hours in 2007 and 2009 (eg,
      OR for some exposure in 2009 was 0.31 95% CI=0.19, 0.51, and OR for full exposure
      0.28 95% CI=0.16, 0.49). Resident satisfaction for many electronic health record
      (EHR)-based features tended to be significantly lower with any exposure (some or
      full) versus no exposure over the study period. For example, the odds ratio for
      resident satisfaction was significantly lower with any exposure to electronic
      health records in continuity practice in 2008, 2009, and 2010 (OR for some
      exposure in 2008 was 0.36; 95% CI=0.19, 0.70, with comparable results in 2009,
      2010). CONCLUSIONS: Resident satisfaction with training was inconsistently
      correlated with exposure to features of PCMH. No correlation between PCMH
      exposure and resident satisfaction was sustained over time.

PMID- 27875603
TI  - EMR-Based Intervention Improves Lead Screening at an Urban Family Medicine
      Practice.
AB  - BACKGROUND AND OBJECTIVES: Elevated blood lead levels have well-described
      detrimental effects to growth and development in children, yet screening rates
      remain low. We sought to determine if a reminder within the electronic health
      record (EHR) could change provider behavior and improve blood lead level (BLL)
      screening test ordering rates in an urban academic family medicine practice.
      METHODS: Baseline BLL test ordering rates were calculated for children ages 9-72
      months. An update adding reminders to screen was made to the electronic note
      template used during pediatric well and sick visits at the practice. Data from
      the 10-week periods both before and after the change was made were compared
      through a retrospective chart review. RESULTS: A total of 210 children were seen
      during the pre-intervention period. Forty-eight percent (n=101) had already been
      screened. Of the 109 eligible for screening, 23 had tests ordered, and 18 of
      those had tests completed. Eighty-four children were eligible for screening in
      the post-intervention period. Forty-one of those children had tests ordered, and
      15 had tests completed. Provider ordering rates increased from 21% of eligible
      patients to 49%. Test completion rates only increased from 17% to 18%.
      CONCLUSIONS: An electronic note-based reminder system significantly improves
      provider ordering rates of BLL tests. Researchers are currently investigating how
      the use of point-of-care BLL sample collection can improve test completion rates
      and therefore increase the frequency of successful screening.

PMID- 27875604
TI  - Integration of Pharmacy Students Into Family Medicine Residency Clinics.
AB  - BACKGROUND AND OBJECTIVES: As interprofessional education opportunities become
      more prevalent within family medicine residency clinics, the benefit of the
      integration of pharmacy students is unclear in the current literature. Our study
      objective was to determine the impact of pharmacy student integration into a
      family medicine residency clinic on family medicine residents' attitudes toward
      interprofessional collaboration and satisfaction. METHODS: Twenty-two pharmacy
      students on clinical rotation were individually paired with family medicine
      residents for approximately 4-5 half days per week over a 10-month period.
      Residents and students were given a pre/post-validated survey on attitudes toward
      interprofessional collaboration. Satisfaction surveys were also administered to
      the residents at the end of the study period. Written components of satisfaction
      surveys were evaluated for commonly occurring themes. RESULTS: Matched survey
      responses were available for over 80% of the residents. Both pre- and post-survey
      responses showed positive attitudes toward physician-pharmacist collaboration. A
      statistically significant positive change was seen for one item in the family
      medicine resident surveys. Favorable written comments revealed positive themes
      toward pharmacy students providing mediation reviews, therapeutic
      recommendations, and patient education. CONCLUSIONS: Pharmacy students can be
      integrated into family medicine residency clinics while maintaining positive
      levels of interprofessional collaboration and providing a perceived benefit to
      the family medicine residents.

PMID- 27875605
TI  - Sustaining Family Physicians in Urban Underserved Settings.
AB  - OBJECTIVE: Our objective was to identify factors that sustain family physicians
      practicing in Milwaukee's underserved urban areas. METHODS: Family physicians
      with clinical careers in Milwaukee's urban, underserved communities were
      identified and invited to participate in a 45-60 minute interview using a
      literature-based semi-structured protocol. Each interview was transcribed and de
      identified prior to independent analysis using a grounded theory qualitative
      approach by two authors to yield sustaining themes. The project was determined
      not human subjects research per Aurora Health Care IRB. RESULTS: Sixteen family
      physicians were identified; six of 11 who met inclusion criteria agreed to
      interview. Four general domains central to sustaining family physicians working
      with underserved populations were identified: (1) cognitive traits and qualities
      (trouble shooting, resilience, flexibility), (2) core values (medicine as
      mechanism to address social justice), (3) skills (self-care, communication,
      clinical management), and (4) support systems (supportive family/employer, job
      flexibility, leadership opportunities, staff function as team). The formation of
      these personal attributes and skills was partly shaped by experiences (from
      childhood to medical training to work experience) and by personal drivers that
      varied by individual. Common was that the challenges of providing care in urban
      underserved settings was seen as rewarding in and of itself and aligned with
      these physicians' values and skills. CONCLUSIONS: Family physicians working with
      underserved populations described possessing a combination of values, cognitive
      qualities, skill sets, and support systems. While family physicians face complex
      challenges in quality care goals in urban underserved settings, training in the
      personal and professional skill sets identified by participants may improve
      physician retention in such communities.

PMID- 27875606
TI  - Precious Parking Lot Provisions of Care: Thoughts From One Mommy, MD.

PMID- 27875607
TI  - Summation.

PMID- 27875609
TI  - Before the Resurrection.

PMID- 27875608
TI  - Keep on Driving.

PMID- 27875610
TI  - The Beautiful Mess of Clinical Research.

PMID- 27875611
TI  - Watch Your Back! How the Back Pain Industry Is Costing Us More and Giving Us
      Less.

PMID- 27875612
TI  - The Story of the Human Body: Evolution, Health and Disease.

PMID- 27875613
TI  - Evidence-Based Education in the Health Professions.

PMID- 27875614
TI  - Teaching Chronic Pain in Family Medicine.

PMID- 27875615
TI  - Reply to "Teaching Chronic Pain in Family Medicine".

PMID- 27875616
TI  - Diversity: Are We Doing Enough?

PMID- 27875617
TI  - The Role of Wheat and Egg Constituents in the Formation of a Covalent and Non
      covalent Protein Network in Fresh and Cooked Egg Noodles.
AB  - Noodles of constant protein content and flour-to-egg protein ratio were made with
      whole egg, egg white, or egg yolk. The optimal cooking time, water absorption,
      and cooking loss of salted whole egg noodles was respectively lower and higher
      than of egg white and egg yolk noodles. However, cooked whole egg noodles showed
      the best Kieffer-rig extensibility. Differences in noodle properties were linked
      to protein network formation. Disulfide bonds in whole egg noodles developed
      faster and to a larger extent during cooking than in egg yolk noodles but slower
      and to a lower extent than in egg white noodles. The balance between the rate of
      protein cross-linking and starch swelling determines cooked noodle properties.
      Ionic and hydrophobic protein interactions increase the optimum cooking time and
      total work in Kieffer-rig extensibility testing of fresh noodles. Hydrogen bonds
      and covalent cross-links are probably the main determinants of the extensibility
      of cooked noodles.

PMID- 27875618
TI  - Implant Treatment in the Predoctoral Clinic: A Retrospective Database Study of
      1091 Patients.
AB  - PURPOSE: This retrospective study was conducted at the Marquette University
      School of Dentistry to (1) characterize the implant patient population in a
      predoctoral clinic, (2) describe the implants inserted, and (3) provide
      information on implant failures. MATERIALS AND METHODS: The study cohort included
      1091 patients who received 1918 dental implants between 2004 and 2012, and had
      their implants restored by a crown or a fixed dental prosthesis. Data were
      collected from patient records, entered in a database, and summarized in tables
      and figures. Contingency tables were prepared and analyzed by a chi-squared test.
      The cumulative survival probability of implants was described using a Kaplan
      Meier survival curve. Univariate and multivariate frailty Cox regression models
      for clustered observations were computed to identify factors associated with
      implant failure. RESULTS: Mean patient age (+/-1 SD) at implantation was 59.7 +/-
      15.3 years; 53.9% of patients were females, 73.5% were Caucasians. Noble Biocare
      was the most frequently used implant brand (65.0%). Most implants had a regular
      size diameter (59.3%). More implants were inserted in posterior (79.0%) than in
      anterior jaw regions. Mandibular posterior was the most frequently restored site
      (43%); 87.8% of implants were restored using single implant crowns. The overall
      implant-based cumulative survival rate was 96.4%. The patient-based implant
      survival rate was 94.6%. Implant failure risk was greater among patients than
      within patients (p < 0.05). Age (>65 years; hazard ratio [HR] = 3.2, p = 0.02),
      implant staging (two-stage; HR = 4.0, p < 0.001), and implant diameter (wide; HR
      = 0.4, p = 0.04) were statistically associated with implant failure. CONCLUSIONS:
      Treatment with dental implants in a supervised predoctoral clinic environment
      resulted in survival rates similar to published results obtained in private
      practice or research clinics. Older age and implant staging increased failure
      risk, while the selection of a wide implant diameter was associated with a lower
      failure risk.

PMID- 27875620
TI  - A reliable technique for ultrasound-guided perineural injection in ulnar
      neuropathy at the elbow.
AB  - INTRODUCTION: Ulnar neuropathy at the elbow (UNE) is a common peripheral
      compression neuropathy and, in most cases, occurs at 2 sites, the
      retroepicondylar groove or the cubital tunnel. With regard to a potential
      therapeutic approach with perineural corticosteroid injection, the aim of this
      study was to evaluate the distribution of injection fluid applied at a standard
      site. METHODS: We performed ultrasound-guided (US-guided) perineural injections
      to the ulnar nerve halfway between the olecranon and the medial epicondyle in 21
      upper limbs from 11 non-embalmed cadavers. In anatomic dissection we investigated
      the spread of injected ink. RESULTS: Ink was successfully injected into the
      perineural sheath of the ulnar nerve in all 21 cases (cubital tunnel: 21 of 21;
      retroepicondylar groove: 19 of 21). CONCLUSION: US-guided injection between the
      olecranon and the medial epicondyle is a feasible and safe method to reach the
      most common sites of ulnar nerve entrapment. Muscle Nerve 56: 237-241, 2017.

PMID- 27875619
TI  - Automated leukocyte processing by microfluidic deterministic lateral
      displacement.
AB  - We previously developed a Deterministic Lateral Displacement (DLD) microfluidic
      method in silicon to separate cells of various sizes from blood (Davis et al.,
      Proc Natl Acad Sci 2006;103:14779-14784; Huang et al., Science 2004;304:987-990).
      Here, we present the reduction-to-practice of this technology with a commercially
      produced, high precision plastic microfluidic chip-based device designed for
      automated preparation of human leukocytes (white blood cells; WBCs) for flow
      cytometry, without centrifugation or manual handling of samples. After a human
      blood sample was incubated with fluorochrome-conjugated monoclonal antibodies
      (mAbs), the mixture was input to a DLD microfluidic chip (microchip) where it was
      driven through a micropost array designed to deflect WBCs via DLD on the basis of
      cell size from the Input flow stream into a buffer stream, thus separating WBCs
      and any larger cells from smaller cells and particles and washing them
      simultaneously. We developed a microfluidic cell processing protocol that
      recovered 88% (average) of input WBCs and removed 99.985% (average) of Input
      erythrocytes (red blood cells) and >99% of unbound mAb in 18 min (average). Flow
      cytometric evaluation of the microchip Product, with no further processing, lysis
      or centrifugation, revealed excellent forward and side light scattering and
      fluorescence characteristics of immunolabeled WBCs. These results indicate that
      cost-effective plastic DLD microchips can speed and automate leukocyte processing
      for high quality flow cytometry analysis, and suggest their utility for multiple
      other research and clinical applications involving enrichment or depletion of
      common or rare cell types from blood or tissue samples. (c) 2016 International
      Society for Advancement of Cytometry.

PMID- 27875621
TI  - Influences of Superheated Steam Roasting and Water Activity Control as Oxidation
      Mitigation Methods on Physicochemical Properties, Lipid Oxidation, and Free Fatty
      Acids Compositions of Roasted Rice.
AB  - The feasibility of using superheated steam roasting and wetting to control the
      water activity in an optimal range to mitigate oxidation of roasted rice was
      evaluated. Changes in the bed temperature as well as rice kernel moisture
      content, water activity, and color were monitored during fluidized bed roasting
      with superheated steam and hot air at 170, 190, and 210  degrees C. Air-roasted
      rice was rewetted to raise its water activity to 0.30 to 0.35. All the samples
      were analyzed for the total oil content, peroxide value (PV), thiobarbituric acid
      (TBA) value, and free fatty acids (FFA) content and compositions. Higher roasting
      temperatures, especially at 210  degrees C, led to a significant increase (P <=
      0.05) in the total oil content of the roasted rice. Wetting led to a significant
      (P <= 0.05) decrease in the TBA value of the air-roasted rice, although the total
      FFA content significantly (P <= 0.05) increased. Rice roasted in superheated
      steam at 210  degrees C exhibited significantly (P <= 0.05) lower PV and TBA
      value; their total FFA content also tended to decrease, which is desirable for a
      longer shelf life.

PMID- 27875622
TI  - Neurographic course Of Wallerian degeneration after human peripheral nerve
      injury.
AB  - INTRODUCTION: Neurographic data on Wallerian degeneration (WD) after motor nerve
      injury are available only from animal studies and human case reports of 9
      patients altogether. A precise knowledge of neurographic features of WD would be
      highly relevant for diagnostic, prognostic, therapeutic, and forensic aspects of
      traumatic lesions. METHODS: We prospectively studied WD in patients with a
      peripheral nerve injury. They underwent sequential neurographic examinations
      beginning no later than 3 days after the injury until a plateau of the amplitude
      of compound muscle action potential was reached. RESULTS: We examined 20 injured
      nerves from 16 patients. Four days after injury, all nerves showed amplitude
      decay to some extent, whereas 85% had reached their plateau at day 8. A length
      dependency of WD could be demonstrated. CONCLUSION: In humans, WD starts no later
      than day 4, shows length dependency, and is completed at day 8 in most nerves.
      Muscle Nerve 56: 247-252, 2017.

PMID- 27875623
TI  - Biophysical characterization of quaternary pyridinium functionalized
      polynorbornenes for DNA complexation and their cellular interactions.
AB  - Cationic polymers with hydrophobic side chains have gained great interest as DNA
      carriers since they form a compact complex with negatively charged DNA phosphate
      groups and interact with the cell membrane. Amphiphilic polyoxanorbornenes with
      different quaternary alkyl pyridinium side chains with ethyl-p(OPy2) and hexyl
      units-p(OPy6) bearing 10 kDa MWT were synthesized by living Ring-Opening
      Metathesis Polymerization method. The physicochemical characteristics: critical
      micellar concentration, size distribution, surface charge, and condensation of
      polymer/DNA complex were investigated. Morphology of complexes was monitored by
      Atomic force microscopy. Cytotoxicity and interaction of these complexes with
      model lipid vesicles mimicking the cell membrane were examined. These polymers
      were enabled to form small sized complexes of DNA, which interact with model
      membrane vesicles. It was found that the nature of hydrophobicity of the
      homopolymers significantly impacts rates of DNA complexation and the surface
      charge of the resulting complexes. These results highlight the prospect of the
      further examinations of these polymers as gene carriers.

PMID- 27875624
TI  - A case of miller fisher syndrome associated with preceding herpes zoster
      ophthalmicus.

PMID- 27875627
TI  - Immunotherapy approaches in the treatment of malignant brain tumors.
AB  - Glioblastoma is the most common malignant primary brain tumor. Despite standard
      of-care treatment, consisting of maximal surgical resection followed by
      chemoradiation, both morbidity and mortality associated with this disease remain
      very poor. Therefore, there is an urgent need for more efficacious and well
      tolerated therapies. Advancing knowledge of the intricate interplay between
      malignant gliomas and the immune system, coupled with the recent launch of
      immunotherapy research for other cancers, has led to a veritable increase in
      immunotherapy investigation for glioblastoma and other malignant gliomas. This
      clinical review highlights the recent breakthroughs in cancer immunotherapy and
      the complex correlation of the immune system with primary brain tumors, with
      special attention to multiple immunotherapy modalities currently being
      investigated for malignant glioma, including peptide vaccines, dendritic cell
      vaccines, oncolytic viruses, chimeric T-cell receptors, and checkpoint
      inhibitors. Cancer 2017;123:734-50. (c) 2016 American Cancer Society.

PMID- 27875625
TI  - Clinical and genetic determinants of ovarian metastases from colorectal cancer.
AB  - BACKGROUND: Ovarian metastases from colorectal cancer (OM-CRC) often are
      unresponsive to chemotherapy and are associated with poor survival. To the
      authors' knowledge, the clinicopathologic and genomic predictors of OM-CRC are
      poorly characterized and optimal clinical management remains unclear. METHODS:
      Women with a histopathological diagnosis of OM-CRC who were treated at Memorial
      Sloan Kettering Cancer Center from 1999 to 2015 were identified. Next-generation
      somatic mutation profiling (Memorial Sloan Kettering-Integrated Mutation
      Profiling of Actionable Cancer Targets [MSK-IMPACT]) was performed on 38 OM-CRC
      cases, including 21 matched tumor pairs/trios. Regression models were used to
      analyze variables associated with progression-free survival and overall survival
      (OS). RESULTS: Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), SMAD family
      member 4 (SMAD4), and neurotrophic receptor tyrosine kinase 1 (NTRK1) mutations
      were more frequent in cases of OM-CRC than in instances of CRC occurring without
      OM. SMAD4 and lysine methyltransferase 2D (KMT2D) mutations were associated with
      reduced OS. Matched multisite tumor sequencing did not identify OM-specific
      genomic alterations. Of the 195 patients who underwent oophorectomy for OM-CRC
      (median age, 49 years with a progression-free survival of 9.4 months and an OS of
      23 months from oophorectomy), 76% had extraovarian metastasis (EOM). In
      multivariable analysis, residual disease after surgery (R2 resection) was
      associated with worse survival. Patients with EOM were less likely to achieve
      R0/R1 surgical resection status (complete macroscopic resection without
      clinical/radiological evidence of disease) (48% vs 94%). However, if R0/R1
      resection status was achieved, both patients with (35.9 months vs 12 months) and
      without (43.2 months vs 14.5 months) EOM were found to have better OS. Among 114
      patients with R0/R1 resection status, 23 (20%) had no disease recurrence,
      including 10 patients (9%) with > 3 years of follow-up. CONCLUSIONS: Loss-of
      function alterations in SMAD4 are frequent and predictive of worse survival in
      patients with OM-CRC. Similar to oligometastatic CRC to the lung or liver,
      surgical resection of OM-CRC is associated with a better outcome only if all
      macroscopic metastatic disease is resected. Cancer 2017;123:1134-1143. (c) 2016
      American Cancer Society.

PMID- 27875626
TI  - Developing a research agenda for reducing the stigma of addictions, part II:
      Lessons from the mental health stigma literature.
AB  - BACKGROUND AND OBJECTIVES: Although advocates and providers identify stigma as a
      major factor in confounding the recovery of people with SUDs, research on
      addiction stigma is lacking, especially when compared to the substantive
      literature examining the stigma of mental illness. METHODS: A comprehensive
      review of the stigma literature that yielded empirically supported concepts and
      methods from the mental health arena was contrasted with the much smaller and
      mostly descriptive findings from the addiction field. In Part I of this two part
      paper (American Journal of Addictions, Vol 26, pages 59-66, this issue),
      constructs and methods from the mental health stigma literature were used to
      summarize research that seeks to understand the phenomena of addiction stigma.
      RESULTS: In Paper II, we use this summary, as well as the extensive literature on
      mental illness stigma change, to outline a research program to develop and
      evaluate strategies meant to diminish impact on public and self-stigma (eg,
      education and contact). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The paper ends
      with recommendations for next steps in addiction stigma research. (Am J Addict
      2017;26:67-74).

PMID- 27875629
TI  - Reply.

PMID- 27875628
TI  - Clinical genomic profiling identifies TYK2 mutation and overexpression in
      patients with neurofibromatosis type 1-associated malignant peripheral nerve
      sheath tumors.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive
      sarcomas that arise at an estimated frequency of 8% to 13% in individuals with
      neurofibromatosis type 1 (NF1). Compared with their sporadic counterparts, NF1
      associated MPNSTs (NF1-MPNSTs) develop in young adults, frequently recur
      (approximately 50% of cases), and carry a dismal prognosis. As such, most
      individuals affected with NF1-MPNSTs die within 5 years of diagnosis, despite
      surgical resection combined with radiotherapy and chemotherapy. METHODS: Clinical
      genomic profiling was performed using 1000 ng of DNA from 7 cases of NF1-MPNST,
      and bioinformatic analyses were conducted to identify genes with actionable
      mutations. RESULTS: A total of 3 women and 4 men with NF1-MPNST were identified
      (median age, 38 years). Nonsynonymous mutations were discovered in 4 genes
      (neurofibromatosis type 1 [NF1], ROS proto-oncogene 1 [ROS1], tumor protein p53
      [TP53], and tyrosine kinase 2 [TYK2]), which in addition were mutated in other
      MPNST cases in this sample set. Consistent with their occurrence in individuals
      with NF1, all tumors had at least 1 mutation in the NF1 gene. Whereas TP53 gene
      mutations are frequently observed in other cancers, ROS1 mutations are common in
      melanoma (15%-35%), another neural crest-derived malignancy. In contrast, TYK2
      mutations are uncommon in other malignancies (<7%). In the current series,
      recurrent TYK2 mutations were identified in 2 cases of NF1-MPNST (30% of cases),
      whereas TYK2 protein overexpression was observed in 60% of MPNST cases using an
      independently generated tissue microarray, regardless of NF1 status. CONCLUSIONS:
      Clinical genomic analysis of the current series of NF1-MPNST cases found that
      TYK2 is a new gene mutated in MPNST. Future work will focus on examining the
      utility of TYK2 expression as a biomarker and therapeutic target for these
      cancers. Cancer 2017;123:1194-1201. (c) 2016 American Cancer Society.

PMID- 27875630
TI  - Eosinophilic fasciitis with subjacent myositis.
AB  - INTRODUCTION: Eosinophilic fasciitis (EF) is a rare disorder that can present
      with muscle symptoms that mimic other neuromuscular diseases. METHODS: We report
      the case of a 43-year-old woman with chronic muscle aches, tightness, and
      stiffness with hypertrophied, well-defined muscles despite physical inactivity,
      and thickened skin with reduced elasticity and discoloration. RESULTS: Except for
      mild peripheral eosinophilia, laboratory studies, including blood count,
      electrolytes, paraneoplastic panel, muscle enzymes, thyroid function, and serum
      protein electrophoresis, were normal. Nerve conduction studies and needle
      electromyography were normal. Magnetic resonance imaging of the thighs
      demonstrated superficial and deep fascial thickening with T2 hyperintensity and
      post-gadolinium enhancement. Fascial and muscle biopsy demonstrated an
      inflammatory exudate in the perimysium and endomysium with fragmented perimysial
      connective tissue and thickened, inflamed fascia. EF was diagnosed. The patient
      was treated with methotrexate and prednisone followed by improvement of muscle
      stiffness and tightness. CONCLUSION: EF should be considered when patients
      present with muscle pain or enlarged muscles. Muscle Nerve 56: 525-529, 2017.

PMID- 27875631
TI  - Intravenous nutrients for preventing inadvertent perioperative hypothermia in
      adults.
AB  - BACKGROUND: Inadvertent perioperative hypothermia (a drop in core temperature to
      below 36 degrees C) occurs because normal temperature regulation is disrupted
      during surgery, mainly because of the effects of anaesthetic drugs and exposure
      of the skin for prolonged periods. Many different ways of maintaining body
      temperature have been proposed, one of which involves administration of
      intravenous nutrients during the perioperative period that may reduce heat loss
      by increasing metabolism, thereby increasing heat production. OBJECTIVES: To
      assess the effectiveness of preoperative or intraoperative intravenous nutrients
      in preventing perioperative hypothermia and its complications during surgery in
      adults. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL; November 2015) in the Cochrane Library; MEDLINE, Ovid SP (1956
      to November 2015); Embase, Ovid SP (1982 to November 2015); the Institute for
      Scientific Information (ISI) Web of Science (1950 to November 2015); and the
      Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCO host;
      1980 to November 2015), as well as the reference lists of identified articles. We
      also searched the Current Controlled Trials website and ClincalTrials.gov.
      SELECTION CRITERIA: Randomized controlled trials (RCTs) of intravenous nutrients
      compared with control or other interventions given to maintain normothermia in
      adults undergoing surgery. DATA COLLECTION AND ANALYSIS: Two review authors
      extracted data and assessed risk of bias for each included trial, and a third
      review author checked details if necessary. We contacted some study authors to
      request additional information. MAIN RESULTS: We included 14 trials (n = 565), 13
      (n = 525) of which compared intravenous administration of amino acids to a
      control (usually saline solution or Ringer's lactate). The remaining trial (n =
      40) compared intravenous administration of fructose versus a control. We noted
      much variation in these trials, which used different types of surgery, variable
      durations of surgery, and different types of participants. Most trials were at
      high or unclear risk of bias owing to inappropriate or unclear randomization
      methods, and to unclear participant and assessor blinding. This may have
      influenced results, but it is unclear how results might have been influenced.No
      trials reported any of our prespecified primary outcomes, which were risk of
      hypothermia and major cardiovascular events. Therefore, we decided to analyse
      data related to core body temperature instead as a primary outcome. It was not
      possible to conduct meta-analysis of data related to amino acid infusion for the
      60-minute and 120-minute time points, as we observed significant statistical
      heterogeneity in the results. Some trials showed that higher temperatures were
      associated with amino acids, but not all trials reported statistically
      significant results, and some trials reported the opposite result, where the
      amino acid group had a lower core temperature than the control group. It was
      possible to conduct meta-analysis for six studies (n = 249) that provided data
      relating to the end of surgery. Amino acids led to a statistically significant
      increase in core temperature in comparison to those receiving control (MD = 0.46
      degrees C 95% CI 0.33 to 0.59; I2 0.0%; random-effects; moderate quality
      evidence).Three trials (n = 155) reported shivering as an outcome. Meta-analysis
      did not show a clear effect, and so it is uncertain whether amino acids reduce
      the risk of shivering (RR 0.36, 95% CI 0.13 to 1.00; I2 = 93%; random-effects
      model; very low-quality evidence). AUTHORS' CONCLUSIONS: Intravenous amino acids
      may keep participants up to a half-degree C warmer than the control. This
      difference was statistically significant at the end of surgery, but not at other
      time points. However, the clinical importance of this finding remains unclear. It
      is also unclear whether amino acids have any effect on the risk of shivering and
      if intravenous nutrients confer any other benefits or harms, as high-quality data
      about these outcomes are lacking.

PMID- 27875634
TI  - The stringent response plays a key role in Bacillus subtilis survival of fatty
      acid starvation.
AB  - The stringent response is a universal adaptive mechanism to protect bacteria from
      nutritional and environmental stresses. The role of the stringent response during
      lipid starvation has been studied only in Gram-negative bacteria. Here, we report
      that the stringent response also plays a crucial role in the adaptation of the
      model Gram-positive Bacillus subtilis to fatty acid starvation. B. subtilis
      lacking all three (p)ppGpp-synthetases (RelBs , RelP and RelQ) or bearing a RelBs
      variant that no longer synthesizes (p)ppGpp suffer extreme loss of viability on
      lipid starvation. Loss of viability is paralleled by perturbation of membrane
      integrity and function, with collapse of membrane potential as the likely cause
      of death. Although no increment of (p)ppGpp could be detected in lipid starved B.
      subtilis, we observed a substantial increase in the GTP/ATP ratio of strains
      incapable of synthesizing (p)ppGpp. Artificially lowering GTP with decoyinine
      rescued viability of such strains, confirming observations that low intracellular
      GTP is important for survival of nutritional stresses. Altogether, our results
      show that activation of the stringent response by lipid starvation is a broadly
      conserved response of bacteria and that a key role of (p)ppGpp is to couple
      biosynthetic processes that become detrimental if uncoordinated.

PMID- 27875633
TI  - Design, Synthesis, and Evaluation of Dasatinib-Amino Acid and Dasatinib-Fatty
      Acid Conjugates as Protein Tyrosine Kinase Inhibitors.
AB  - Derivatives of the tyrosine kinase inhibitor dasatinib were synthesized by
      esterification with 25 carboxylic acids, including amino acids and fatty acids,
      thereby extending the drug to interact with more diverse sites and to improve
      specificity. The dasatinib-l-arginine derivative (Das-R, 7) was found to be the
      most potent of the inhibitors tested, with IC50 values of 4.4, <0.25, and <0.45
      nm against Csk, Src, and Abl kinases, respectively. The highest selectivity ratio
      obtained in our study, 91.4 Csk/Src, belonged to compound 18 (Das-C10 ) with an
      IC50 value of 3.2 MUm for Csk compared with 35 nm for Src. Furthermore, many
      compounds displayed increased selectivity toward Src over Abl. Compounds 15 (Das
      glutamic acid) and 13 (Das-cysteine) demonstrated the largest gains (10.2 and
      10.3 Abl/Src IC50 ratios). Das-R (IC50 =2.06 MUm) was significantly more potent
      than the parent dasatinib (IC50 =26.3 MUm) against Panc-1 cells, whereas both
      compounds showed IC50 <51.2 pm against BV-173 and K562 cells. Molecular modeling
      and binding free energy simulations revealed good agreements with the
      experimental results and rationalized the differences in selectivity among the
      studied compounds. Integration of experimental and computational approaches in
      the design and biochemical screening of dasatinib derivatives facilitated
      rational engineering and diversification of the dasatinib scaffold, providing
      useful insight into mechanisms of kinase selectivity.

PMID- 27875632
TI  - Variable phenotypic expression and onset in MYH14 distal hereditary motor
      neuropathy phenotype in a large, multigenerational North American family.
AB  - INTRODUCTION: Distal hereditary motor neuropathy (dHMN) causes distal-predominant
      weakness without prominent sensory loss. Myosin heavy chain disorders most
      commonly result in distal myopathy and cardiomyopathy with or without hearing
      loss, but a complex phenotype with dHMN, myopathy, hoarseness, and hearing loss
      was reported in a Korean family with a c.2822G>T mutation in MYH14. In this study
      we report phenotypic features in a North American family with the c.2822G>T in
      MYH14. METHODS: Clinical and molecular characterization was performed in a large,
      6-generation, Caucasian family with MYH14 dHMN. RESULTS: A total of 11 affected
      and 7 unaffected individuals were evaluated and showed varying age of onset and
      severity of weakness. Genotypic concordance was confirmed with molecular
      analysis. Electrophysiological studies demonstrated distal motor axonal
      degeneration without myopathy in all affected subjects tested. CONCLUSION:
      Mutation of MYH14 can result in a range of neuromuscular phenotypes that includes
      a dHMN and hearing loss phenotype with variable age of onset. Muscle Nerve 56:
      341-345, 2017.

PMID- 27875635
TI  - Muscle adaptations following 21 consecutive days of strength test familiarization
      compared with traditional training.
AB  - INTRODUCTION: Large increases in 1-repetition maximum (1RM) strength have been
      demonstrated from repeated testing, but it is unknown whether these increases can
      be augmented by resistance training. METHODS: Five trained individuals performed
      a 1RM test and maximal voluntary isometric contraction (MVC) for unilateral elbow
      flexion exercise on 1 arm (testing arm), while the other arm performed a 1RM test
      and MVC, in addition to 3 sets of exercise (70% 1RM) (training arm), for 21
      straight days. RESULTS: Although only the training arm had increased muscle
      thickness [mean 0.28 cm, 95% confidence interval (CI) 0.22-0.33 cm], 1RM strength
      increased similarly in the training (2.2 kg, 95% CI 0.9-3.4 kg; P = 0.008) and
      testing (1.9 kg, 95% CI 0.5-3.2 kg; P = 0.019) arms. CONCLUSION: Increases in 1RM
      strength from resistance training are related to the specificity of exercise and
      are likely driven by mechanisms other than muscle growth. Muscle Nerve 56: 307
      314, 2017.

PMID- 27875636
TI  - Evaluation of coronary artery disease in potential liver transplant recipients.
AB  - Improvements in the management of patients undergoing liver transplantation (LT)
      have resulted in a significant increase in survival in recent years. Cardiac
      disease is now the leading cause of early mortality, and the stress of major
      surgery, hemodynamic shifts, and the possibilities of hemorrhage or reperfusion
      syndrome require the recipient to have good baseline cardiac function. The
      prevalence of coronary artery disease (CAD) is increasing in LT candidates,
      especially in those with nonalcoholic fatty liver disease. In assessing LT
      recipients, we suggest a management paradigm of "quadruple assessment" to include
      (1) history, examination, and electrocardiogram; (2) transthoracic
      echocardiogram; (3) functional testing; and (4) where appropriate, direct
      assessment of CAD. The added value of functional testing, such as cardiopulmonary
      exercise testing, has been shown to be able to predict posttransplant
      complications independently of the presence of CV disease. This approach gives
      the assessment team the greatest chance of detecting and preventing complications
      related to CAD. Liver Transplantation 23 386-395 2017 AASLD.

PMID- 27875637
TI  - AMBRA1, a novel alpha-synuclein-binding protein, is implicated in the
      pathogenesis of multiple system atrophy.
AB  - The accumulation of abnormal alpha-synuclein is the major histopathological
      feature of Lewy body disease and multiple system atrophy (MSA), which are
      referred to as synucleinopathies. Cytoplasmic degradation systems, such as the
      autophagy-lysosome and proteasome pathways, are involved in their pathogenesis.
      Autophagy is tightly regulated by several upstream proteins including UNC-51-like
      kinase 1/2, beclin1, vacuolar protein sorting-associated protein 34 and
      autophagy/beclin1 regulator 1 (AMBRA1). Recently, we revealed that both cortical
      and brainstem-type Lewy bodies were immunopositive for several upstream proteins
      of autophagy. Therefore, we conducted the present study to elucidate the role of
      upstream proteins of autophagy in the pathogenesis of MSA. Pathological and
      biochemical analyses using human brain samples revealed that AMBRA1 is a
      component of the pathological hallmarks of MSA and upstream proteins of autophagy
      are impaired in the MSA brain. In vitro and in vivo analyses revealed a ninefold
      stronger affinity of AMBRA1 with alpha-synuclein phosphorylated at serine 129
      compared with non-phosphorylated alpha-synuclein. Furthermore, a weak but
      significant correlation between AMBRA1 overexpression and reduction of abnormal
      alpha-synuclein was observed. Silencing AMBRA1 function caused aggregates of
      alpha-synuclein in the cytoplasm of mouse primary cultured neurons, which was
      simulated by the treatment of Bafilomycin, an autophagy inhibitor. Our results
      demonstrated for the first time that AMBRA1 is a novel hub binding protein of
      alpha-synuclein and plays a central role in the pathogenesis of MSA through the
      degradative dynamics of alpha-synuclein. These results raise the possibility that
      molecular modulation targeting AMBRA1 can be a promising candidate for the
      treatment of synucleinopathies.

PMID- 27875638
TI  - Sensory Quality Preservation of Coated Walnuts.
AB  - The objective of this study was to evaluate the sensory stability of coated
      walnuts during storage. Four walnut samples were prepared: uncoated (NC), and
      samples coated with carboxymethyl cellulose (NCMC), methyl cellulose (NMC), or
      whey protein (NPS). The samples were stored at room temperature for 210 d and
      were periodically removed from storage to perform a sensory descriptive analysis.
      A consumer acceptance test was carried out on the fresh product (storage day 0)
      to evaluate flavor. All samples exhibited significant differences in their
      sensory attributes initially and after storage. Intensity ratings for oxidized
      and cardboard flavors increased during storage. NC showed the highest oxidized
      and cardboard intensity ratings (39 and 22, respectively) and NMC exhibited the
      lowest intensity ratings for these negative attributes (8 and 17, respectively)
      after 210 d of storage. Alternatively, the intensity ratings for sweetness and
      walnut flavors were decreased for all samples. NMC had the lowest decrease at the
      end of storage for these positive attributes (75.86 in walnut flavor and 12.09 in
      sweetness). The results of this study suggest a protective effect of the use of
      an edible coating to preserve sensory attributes during storage, especially for
      samples coated with MC. The results of the acceptance test showed that addition
      of the coating negatively affected the flavor acceptance for NMC and NCMC coated
      walnuts. Edible coatings help to preserve sensory attributes in walnuts,
      improving their shelf-life, however, these coatings may affect consumer
      acceptance in some cases.

PMID- 27875639
TI  - Longterm follow-up of small pancreatic cystic lesions in liver transplant
      recipients.
AB  - Incidental small pancreatic cystic lesions (PCLs) are often found on preoperative
      imaging in patients undergoing orthotopic liver transplantation (OLT). Although
      these are considered benign or of low malignant potential, the influence of
      immunosuppression after OLT may be of concern. The aim of this study was to
      observe the longterm outcome of these small PCLs in post-OLT patients. An
      institutional OLT database of 1778 consecutive OLT patients from January 2000 to
      December 2010 was analyzed. Computed tomography, magnetic resonance imaging, or
      endoscopic ultrasound at the time of OLT and all subsequent imaging, cytology,
      fluid analysis of PCLs, and patient status were evaluated. A total of 70 patients
      with 182 PCLs, of benign or low malignant potential, were identified with a mean
      follow-up time of 64 months. At initial diagnosis of PCLs in 48 patients, 7
      branch duct-type intraductal papillary mucinous neoplasms (B-IPMNs), 1 serous
      cystadenoma (SCA), and 40 nonspecific benign cysts were identified. Final
      diagnosis at the end of the follow-up revealed 16 B-IPMNs, 3 SCAs, and a mixed
      acinar-neuroendocrine carcinoma, in which the latter developed 9 years after
      initial diagnosis of B-IPMN. During the follow-up time, average increase in size
      and number of PCLs were 4.5 mm and 1.4, respectively (P < 0.001 for both). The
      majority of incidental PCLs in OLT patients showed an indolent behavior despite
      immunosuppression. Risk of malignancy development was very low and comparable
      with normal population. Liver Transplantation 23 324-329 2017 AASLD.

PMID- 27875641
TI  - Saving Science by Doing Less of It?
AB  - In the current issue of The New Atlantis, Daniel Sarewitz, professor of science
      and society at Arizona State University, argues that science is broken because it
      is managed and judged by scientists themselves, operating under Vannevar Bush's
      famous 1945 declaration that scientific progress depends on the "free play of
      free intellects ... dictated by their curiosity." With that scientific agenda,
      society ends up with a lot of unnecessary, uncoordinated, and unproductive
      research. To save science, holds Sarewitz, we need to put it in the hands of
      people who are looking for practical solutions to specific problems. In one
      article in this issue of the Hastings Center Report (November-December 2016),
      Kirstin Borgerson poses a question in this same conceptual space: are there too
      many clinical trials? Other pieces in the issue cover a mix of topics: the lead
      article addresses some of the challenges that will have to be faced as
      "artificial organs" become available, a third article looks at how crowdfunding
      sites like GoFundMe can be used to make public appeals for medical funding, and a
      special report found in a supplement to the issue offers a round of analysis and
      recommendations about the provision of medical care to professional football
      players.

PMID- 27875640
TI  - An untold story: The important contributions of Muslim scholars for the
      understanding of human anatomy.
AB  - It is usually assumed that Galen is one of the fathers of anatomy and that
      between the Corpus Galenicum and the Renaissance there was no major advance in
      anatomical knowledge. However, it is also consensually accepted that Muslim
      scholars had the intellectual leadership from the 8th/9th to 13th centuries, and
      that they made remarkable progresses in numerous scientific fields including
      medicine. So, how is it possible that they did not contribute to advance human
      anatomy during that period? According to the dominant view, Muslim scholars
      exclusively had a passive role: their transmission of knowledge from the Greeks
      to the West. Here, we summarize, for the first time in a single paper, the
      studies of major Muslim scholars that published on human anatomy before Vesalius.
      This summary is based on analyses of original Arabic texts and of more recent
      publications by anatomists and historians, and on comparisons between the
      descriptions provided by Galen and by these Muslim scholars. We show that Arabic
      speakers and Persians made important advances in human anatomy well before
      Vesalius. The most notable exception concerns the muscular system: strikingly,
      there were apparently neither advances made by Muslims nor by Westerners for more
      than 1000 years. Unbiased discussions of these and other related issues, and
      particularly of the mainly untold story about the major contributions of Muslim
      scholars to anatomy, are crucial to our knowledge of the history of anatomy,
      biology and sciences, and also of our way of thinking, biases, and prejudices.
      Anat Rec, 300:986-1008, 2017. (c) 2017 Wiley Periodicals, Inc.

PMID- 27875642
TI  - International Perspectives on Physician Assistance in Dying.
AB  - When the Supreme Court of Canada recognized a constitutional right to "medical
      assistance in dying" last year-and the nation's Parliament enacted legislation to
      implement the right earlier this year-Canadian lawmakers could look to two
      different models for guidance. The Netherlands and Belgium recognize a broad
      right to assistance in dying, while Oregon and elsewhere in the United States
      have a narrow right. In some ways, assistance in dying in Canada follows the
      Dutch-Belgian approach, while, in other ways, it seems more American. Two
      societal factors seem relevant to the different approaches: the role that
      religion plays in people's lives and the trust that people place in their
      governments and health care systems. As other governments consider legalizing
      assistance in dying, an important question is whether some restrictions on the
      right are particularly critical. The experience to date suggests that requiring
      patients to be terminally ill has provided the best protection against misuse.

PMID- 27875643
TI  - Crowdfunding FOR MEDICAL CARE: Ethical Issues in an Emerging Health Care Funding
      Practice.
AB  - Crowdfunding websites allow users to post a public appeal for funding for a range
      of activities, including adoption, travel, research, participation in sports, and
      many others. One common form of crowdfunding is for expenses related to medical
      care. Medical crowdfunding appeals serve as a means of addressing gaps in medical
      and employment insurance, both in countries without universal health insurance,
      like the United States, and countries with universal coverage limited to
      essential medical needs, like Canada. For example, as of 2012, the website
      Gofundme had been used to raise a total of 8.8 million dollars (U.S.) for seventy
      six hundred campaigns, the majority of which were health related. This money can
      make an important difference in the lives of crowdfunding users, as the costs of
      unexpected or uninsured medical needs can be staggering. In this article, I offer
      an overview of the benefits of medical crowdfunding websites and the ethical
      concerns they raise. I argue that medical crowdfunding is a symptom and cause of,
      rather than a solution to, health system injustices and that policy-makers should
      work to address the injustices motivating the use of crowdfunding sites for
      essential medical services. Despite the sites' ethical problems, individual users
      and donors need not refrain from using them, but they bear a political
      responsibility to address the inequities encouraged by these sites. I conclude by
      suggesting some responses to these concerns and future directions for research.

PMID- 27875644
TI  - Skepticism in the Genomic Era.
AB  - I joined The Hastings Center this past summer, after graduating from Duke
      University, where I researched advancements in neuroscience and genomics and
      their import for law, ethics, and policy. This research required, to an extent,
      faith in the idea that researchers can identify pathways by which genes combine
      with epigenetic and environmental factors to affect neuronal activity and
      influence behaviors. Throughout my first months here, I have puzzled over broad
      critiques of "genomic hype" in recent literature, which clash with the optimistic
      rhetoric found in the Human Genome Project and the Precision Medicine Initiative.

PMID- 27875646
TI  - Bartleby in the NICU.
AB  - The doctors were frustrated. They could see only two options. Neither was very
      desirable. They could stop the ventilator and let the baby die. Or they could do
      a tracheostomy and start preparations to discharge him on a ventilator. The
      parents wanted a third option. They kept hoping that their baby would get better.
      The doctors were pretty sure that that wasn't going to happen.

PMID- 27875647
TI  - What Pacemakers Can Teach Us about the Ethics of Maintaining Artificial Organs.
AB  - One day soon it may be possible to replace a failing heart, liver, or kidney with
      a long-lasting mechanical replacement or perhaps even with a 3-D printed version
      based on the patient's own tissue. Such artificial organs could make transplant
      waiting lists and immunosuppression a thing of the past. Supposing that this
      happens, what will the ongoing care of people with these implants involve? In
      particular, how will the need to maintain the functioning of artificial organs
      over an extended period affect patients and their doctors and the
      responsibilities of those who manufacture such devices? Drawing on lessons from
      the history of the cardiac pacemaker, this article offers an initial survey of
      the ethical issues posed by the need to maintain and service artificial organs.
      We briefly outline the nature and history of cardiac pacemakers, with a
      particular focus on the need for technical support, maintenance, and replacement
      of these devices. Drawing on the existing medical literature and on our
      conversations and correspondence with cardiologists, regulators, and
      manufacturers, we describe five sources of ethical issues associated with
      pacemaker maintenance: the location of the devices inside the human body, such
      that maintenance generates surgical risks; the complexity of the devices, which
      increases the risk of harms to patients as well as introducing potential
      injustices in access to treatment; the role of software-particularly software
      that can be remotely accessed-in the functioning of the devices, which generates
      privacy and security issues; the impact of continual development and improvement
      of the device; and the influence of commercial interests in the context of a
      medical device market in which there are several competing products. Finally, we
      offer some initial suggestions as to how these questions should be answered.

PMID- 27875648
TI  - MANUSCRIPT REVIEWERS 2016.

PMID- 27875649
TI  - Competence in Plain English.
AB  - Like many other bioethicists, I often give talks on clinical topics that may
      touch on the patient's right of autonomy with regard to medical treatment and,
      from there, may move to questions about whether said patient has the capacity to
      exercise said right. When I get to that subject, I might ask, "Is this person
      competent to refuse treatment?" A stunned silence falls over the room, until
      finally a hand shoots up. "'Competent' is a legal term," I am instructed. "Don't
      you mean to ask whether he has the capacity to make decisions for himself?" The
      tone suggests that I'm being helped to make a very important distinction. But
      it's not a very important distinction; and it's misleading to boot.

PMID- 27875650
TI  - Military Genitourinary Trauma: Policies, Implications, and Ethics.
AB  - The men and women who serve in the armed forces, in the words of Major General
      Joseph Caravalho, "sign a blank check, co-signed by their families, payable to
      the Army, Navy, Air Force, or Marines, up to and including their lives." It is
      human nature to consider such a pact in polarized terms; the pact concludes in
      either a celebratory homecoming or funereal mourning. But in reality, surviving
      catastrophic injury may incur the greatest debt. The small but real possibility
      of losing the ability to bear biological children due to genitourinary combat
      injury has been a topic of discussion in hushed tones, behind closed doors. But
      as policy changes move the conversation into the open, we must be fully aware of
      the far-reaching and long-term impacts of decisions on those who have sustained
      genitourinary injury. In January 2016, Secretary of Defense Ashton Carter
      outlined a set of reforms that would improve the quality of life for military
      families by recognizing the importance of maintaining fertility, even in the face
      of severe injury. This first promising step could build a solid foundation of
      insuring fertility preservation for wounded service members with genitourinary
      injury, and it could set a precedent beyond the military for insuring treatment
      for people who have lost their reproductive capacity. Thus, the ethical
      challenges raised by the new policy require careful analysis.

PMID- 27875651
TI  - Religious Hospitals and Patient Choice.
AB  - Recent media reports have drawn widespread attention to the experiences of
      patients who are denied reproductive services at Catholic hospitals. For some
      patients, such as those experiencing miscarriage, denial of appropriate treatment
      can lead to serious health consequences. However, many patients are unaware of
      the limitations on services available at religiously affiliated health care
      institutions. As a result, patients' ability to make informed and autonomous
      decisions about where to seek treatment is hindered. There are currently no
      federal or state laws requiring health care institutions to inform patients
      directly of the full scope of medical services they are unable to provide on the
      basis of religion or conscience. Given religious hospitals' significant role in
      the provision of health care in the United States, it is essential that patients
      be clearly informed about institutional limitations on care. This goal would be
      best served by adopting a federal disclosure law similar to the Patient Self
      Determination Act.

PMID- 27875652
TI  - Sample preparation for flow cytometry benefits from some lateral thinking.

PMID- 27875653
TI  - Low Rate of Progression to Ankylosing Spondylitis Among Patients With Presumed
      Nonradiographic Axial Spondyloarthritis: Comment on the Article by Wang et al.

PMID- 27875654
TI  - Biological Risks to Public Health: Lessons from an International Conference to
      Inform the Development of National Risk Communication Strategies.
AB  - Biological risk management in public health focuses on the impact of outbreaks on
      health, the economy, and other systems and on ensuring biosafety and biosecurity.
      To address this broad range of risks, the International Health Regulations (IHR,
      2005) request that all member states build defined core capacities, risk
      communication being one of them. While there is existing guidance on the
      communication process and on what health authorities need to consider to design
      risk communication strategies that meet the requirements on a governance level,
      little has been done on implementation because of a number of factors, including
      lack of resources (human, financial, and others) and systems to support effective
      and consistent capacity for risk communication. The international conference on
      "Risk communication strategies before, during and after public health
      emergencies" provided a platform to present current strategies, facilitate
      learning from recent outbreaks of infectious diseases, and discuss
      recommendations to inform risk communication strategy development. The discussion
      concluded with 4 key areas for improvement in risk communication: consider
      communication as a multidimensional process in risk communication, broaden the
      biomedical paradigm by integrating social science intelligence into epidemiologic
      risk assessments, strengthen multisectoral collaboration including with local
      organizations, and spearhead changes in organizations for better risk
      communication governance. National strategies should design risk communication to
      be proactive, participatory, and multisectoral, facilitating the connection
      between sectors and strengthening collaboration.

PMID- 27875655
TI  - Postoperative Pain Evaluation After Robotic Transaxillary Thyroidectomy Versus
      Conventional Thyroidectomy: A Prospective Study.
AB  - BACKGROUND: Robot-assisted transaxillary thyroidectomy (RATT) is an emerging
      technique with excellent cosmetic results but is supposedly more invasive and
      painful than conventional thyroidectomy (CT). This prospective study compared
      pain after RATT and CT. METHODS: Inclusion criteria were a nodule <5 cm and
      volume <30 mL. Patients received the same analgesia. Pain was evaluated by visual
      analog scale (VAS) in the recovery room (VASrr), on the first postoperative day
      at 8:00 a.m. (VAS 8 a.m.) and 8:00 p.m. (VAS 8 p.m.), at 8:00 a.m. on the second
      postoperative day (VAS 8*a.m.), and after 7 days (VAS 7). Operative time and
      complications were evaluated. RESULTS: From May 2015 to September 2015, 124
      patients (all women) underwent thyroidectomy: 62 underwent RATT and 62 underwent
      CT. Mean age was 39.7 +/- 10.2 years in the RATT group and 41.4 +/- 12.5 years in
      the CT group. Groups were comparable for thyroid volume and nodule diameter.
      Operative time was longer in the RATT group than in the CT group (119.4 +/- 25.5
      versus 70.3 +/- 11.0 minutes). Complications were three transient hypocalcemia in
      RATT and four in the CT group. No definitive complications occurred. VASrr was
      lower in the RATT group (1.79 +/- 2.06 versus 2.5 +/- 1.18; P < .0001). There was
      no difference between groups for VAS 8 a.m., VAS 8 p.m., and VAS 8*a.m., but VAS
      7 was higher in the RATT group (0.85 +/- 1.77 versus 0.17 +/- 0.52; P < .010).
      DISCUSSION: RATT is as safe and effective as CT. Patients undergoing RATT,
      surprisingly, experienced less pain in the immediate postoperative period.
      However, the VAS 7 score was higher in the RATT group, probably because the
      intact neck is favorable in the early phase of recovery, but the large dissection
      takes longer for healing.

PMID- 27875657
TI  - Characterization of Macrophage-Activating Polysaccharide Isolated from Fermented
      Brown Rice.
AB  - Brown rice has nutritional benefits due to its abundant nutrients and high
      dietary fiber content. However, it is often consumed in a fermented form for
      improved chewy texture and digestibility. In this study, a polysaccharide, FBR
      4a, was isolated from fermented brown rice and its chemical composition was
      analyzed. In addition, its immune-stimulating activity was determined using
      RAW264.7 cells. FBR-4a is a carbohydrate and consists of nine types of
      monosaccharides, including galactose, arabinose, rhamnose, mannose, fucose,
      xylose, glucose, galacturonic acid, and glucuronic acid. FBR-4a increased the
      gene expression of iNOS and IL-6 and enhanced the production of immune
      stimulatory molecules (nitric oxide [NO], IL-6, and TNF-alpha) in RAW264.7 cells.
      Western blot analysis showed that FBR-4a phosphorylated the mitogen-activated
      protein kinases, NF-kappaB and c-Jun (major component of AP-1 transcription
      factor) in RAW264.7 cells, in a concentration-dependent manner. FBR-4a-induced IL
      6 and NO production was completely suppressed by IkappaBalpha and JNK inhibition,
      but not by ERK and p38 inhibition. Furthermore, the phosphorylation of c-Jun was
      also suppressed by IkappaBalpha and JNK inhibition. These findings suggest that
      FBR-4a isolated from fermented brown rice has immune potentiation activity on
      macrophages through IkappaBalpha and JNK signaling pathways, which play a central
      role in IL-6 and NO production.

PMID- 27875656
TI  - Involvement of c-Jun N-Terminal Kinase in TNF-alpha-Driven Remodeling.
AB  - Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is
      characterized by airway wall thickening and/or emphysema. Although the bronchial
      and alveolar compartments are functionally independent entities, we recently
      showed comparable alterations in matrix composition comprised of decreased
      elastin content and increased collagen and hyaluronan contents of alveolar and
      small airway walls. Out of several animal models tested, surfactant protein C
      (SPC)-TNF-alpha mice showed remodeling in alveolar and airway walls similar to
      what we observed in patients with COPD. Epithelial cells are able to undergo a
      phenotypic shift, gaining mesenchymal properties, a process in which c-Jun N
      terminal kinase (JNK) signaling is involved. Therefore, we hypothesized that TNF
      alpha induces JNK-dependent epithelial plasticity, which contributes to lung
      matrix remodeling. To this end, the ability of TNF-alpha to induce a phenotypic
      shift was assessed in A549, BEAS2B, and primary bronchial epithelial cells, and
      phenotypic markers were studied in SPC-TNF-alpha mice. Phenotypic markers of
      mesenchymal cells were elevated both in vitro and in vivo, as shown by the
      expression of vimentin, plasminogen activator inhibitor-1, collagen, and matrix
      metalloproteinases. Concurrently, the expression of the epithelial markers, E
      cadherin and keratin 7 and 18, was attenuated. A pharmacological inhibitor of JNK
      attenuated this phenotypic shift in vitro, demonstrating involvement of JNK
      signaling in this process. Interestingly, activation of JNK signaling was also
      clearly present in lungs of SPC-TNF-alpha mice and patients with COPD. Together,
      these data show a role for TNF-alpha in the induction of a phenotypic shift in
      vitro, resulting in increased collagen production and the expression of elastin
      degrading matrix metalloproteinases, and provide evidence for involvement of the
      TNF-alpha-JNK axis in extracellular matrix remodeling.

PMID- 27875658
TI  - Development and psychometric properties of the sound preference and hearing
      habits questionnaire (SP-HHQ).
AB  - OBJECTIVE: The aim of the study was, based on the individualisation of hearing
      aids (HA) and pre-sets for audio devices, to develop a questionnaire to determine
      the basis for profiling sound preferences and hearing habits to gather additional
      information usable for HA fitting and adjustment tools for audio-devices.
      METHODS: We developed a questionnaire consisting of 46 items. A postal survey was
      conducted with N = 622 users with a mean age of 66 years (47.9% aided with HA,
      45.7% female). RESULTS: Seven factors were identified by means of Explanatory and
      Confirmatory Factor Analyses: F1: 'Annoyance/distraction by background noise',
      F2: 'Importance of sound quality', F3: 'Noise Sensitivity', F4: 'Avoidance of
      unpredictable sounds', F5: 'Openness towards loud/new sounds', F6: 'Preferences
      for warm sounds', and F7: 'Details of environmental sounds/music'. Only the first
      of these factors was related to the audiogram of the user. No difference with any
      of the factors could be observed with HA use/non-use. In contrast, gender effects
      were found with female respondents preferring warm sounds and being more
      sensitive to noise. CONCLUSIONS: The sound preference and hearing habits
      questionnaire (SP-HHQ) is a usable tool for profiling the users with respect to
      sound preferences relevant for HA fitting and pre-sets for audio devices.

PMID- 27875659
TI  - Upregulated Expression of microRNA-16 Correlates with Th17/Treg Cell Imbalance in
      Patients with Rheumatoid Arthritis.
AB  - To explore the correlation between miR-16 expression in T cells of peripheral
      blood mononuclear cells (PBMCs) and Th17/Treg imbalance in rheumatoid arthritis
      (RA) patients. Forty RA patients were recruited as the case group and further
      grouped as active RA and inactive RA groups; 21 healthy individuals were selected
      as the control group. Th17 and Treg were measured by flow cytometry, and their
      related cytokines were measured by FlowCytomix. RORgammat, FoxP3 mRNA, and miR-16
      expression in T cells was determined by real-time quantitative polymerase chain
      reaction. Western blotting was performed to measure RORgammat and FoxP3 protein
      expression. RA patients showed upregulated Th17 and RORgammat mRNA and protein
      expression compared with the controls (all p < 0.05); active RA patients showed
      lower Treg and FoxP3 mRNA and protein expression compared with inactive RA
      patients and controls (all p < 0.05). Secretion levels of Th17-related cytokines
      were higher in active RA patients than in inactive RA patients and controls (all
      p < 0.05); whereas those of Treg-related cytokines were lower in active RA
      patients than in controls (all p < 0.05). Active RA patients showed increased miR
      16 expression in Th17 cells and decreased miR-16 expression in Treg cells of
      PBMCs (both p < 0.05). Pearson's test showed that in the PBMCs of the RA
      patients, miR-16 expression in the Th17 cells was positively related with
      RORgammat mRNA expression, and miR-16 expression in the Treg cells was positively
      related with FoxP3 mRNA expression (both p < 0.05). The expression of miR-16 in
      Th17 and Treg cells of PBMCs in RA patients was closely associated with the
      expression of RORgammat and FoxP3. MiR-16 may be involved in Th17/Treg imbalance
      of RA patients by affecting the expression of RORgammat and FoxP3.

PMID- 27875660
TI  - Successful Use of Targeted Temperature Management After Repair of Myocardial
      Rupture from Blunt Chest Trauma: A Case Report.
AB  - Targeted temperature management (TTM) improves survival and neurological outcome
      after nontraumatic cardiac arrest. However, TTM is not used widely after
      traumatic cardiac arrest because of concerns that it might exacerbate bleeding.
      We report the use of postarrest TTM after repair of blunt myocardial rupture. A
      48-year-old man was admitted after being rescued from a major traffic accident by
      the local emergency service. Focused sonography showed pericardial fluid without
      cardiac tamponade. Computed tomography showed a large hematoma in the anterior
      mediastinum associated with hemopericardium. The patient developed cardiac arrest
      during the operative preparations. Repeat bedside sonography revealed a large
      pericardial effusion and signs of cardiac tamponade. Spontaneous circulation was
      restored after ultrasound-guided pericardiocentesis. His Glasgow Coma Scale score
      was 3. The patient was transported promptly to the operating room and underwent
      median sternotomy without cardiopulmonary bypass. A rupture of the junction of
      the superior vena cava/right atrium and left atrial appendage was detected and
      was closed by direct suturing. Immediately after return to the intensive care
      unit, we performed TTM (target body temperature 34.5 degrees C) using a surface
      cooling device at 4 hours postarrest. TTM was maintained for 24 hours and
      controlled gradual rewarming was then initiated. He regained consciousness 36
      hours postrewarming with limited speech ability. The patient recovered with no
      further cardiac events and was discharged 3 weeks after admission, with no other
      serious complications. The patient was neurologically intact (cerebral
      performance category 1) at 6 months of follow-up. This case demonstrates the
      potential benefit and applicability of postarrest TTM in patients after repair of
      blunt myocardial rupture.

PMID- 27875661
TI  - Deployment of the Philadelphia Medical Reserve Corps for the 2015 Papal Visit and
      the 2016 Democratic National Convention.

PMID- 27875662
TI  - Influence of Age and Dose of African Swine Fever Virus Infections on Clinical
      Outcome and Blood Parameters in Pigs.
AB  - African swine fever (ASF) is a fatal disease for domestic pigs, leading to
      serious economic losses in countries where ASF is endemic. Despite extensive
      research, efficient vaccines against ASF are lacking. Since peripheral blood
      cells are important mediators for vaccines, we study the impact of ASF on blood
      parameters in pigs with different ages and infected with different doses of ASF
      virus. Four different groups were studied: (1) 12 weeks of age/low virus dose;
      (2) 12 weeks of age/high virus dose; (3) 18 weeks of age/low virus dose; and (4)
      18 weeks of age/high virus dose. By varying in age and/or ASFV inoculation dose,
      we monitor blood parameters during different degrees of disease. Thirty percent
      of the pigs survived the infection with a moderately virulent strain of African
      swine fever virus (ASFV). Animals that did survive infection were generally
      older, independent from the inoculation dose used. A firm reduction in many
      different cell types at 3-5 days postinfection (DPI) was accompanied by an
      increase in body temperature, followed by clinical signs and mortality from day 6
      PI. While blood parameters generally normalized in survivors, gammadelta T cells
      and IL-10 levels could be related to mortality. These conclusions should be
      considered in new approaches for protection against ASF.

PMID- 27875663
TI  - Cross-Reactive Potential of HIV-1 Subtype C-Infected Indian Individuals Against
      Multiple HIV-1 Potential T Cell Epitope Gag Variants.
AB  - Vaccine immunogen with expanded T cell coverage for protection against HIV-1
      diversity is the need of the hour. This study was undertaken to examine the
      ability of T cells to respond to a broad spectrum of potential T cell epitope
      (PTE) peptides containing variable as well as conserved sequences that would most
      accurately reflect immune responses to different circulating strains. Set of 320
      PTE peptides were pooled in a matrix format that included 40 pools of 32 peptides
      per pool. These pools were used in interferon-gamma enzyme-linked immunospot
      assay for screening and confirmation of HIV-1 PTE Gag-specific T cell immune
      responses in 34 HIV-1 seropositive Indian individuals. "Deconvolute This"
      software was used for result analysis. The dominant target in terms of magnitude
      and breadth of responses was observed to be the p24 subunit of Gag protein. Of
      the 34 study subjects, 26 (77%) showed a response to p24 PTE Gag peptides, 17
      (50%) to p17, and 17 (50%) responded to p15 PTE peptides. The total breadth and
      magnitude of immune response ranged from 0.75 to 14.50 and 95.02 to 1,103 spot
      forming cells/106 cells, respectively. Seventy-six peptides located in p24 Gag
      were targeted by 77% of the study subjects followed by 51 peptides in p17 Gag and
      46 peptides in p15 Gag with multiple variants being recognized. Maximum study
      participants recognized PTE peptide sequence Gag271->285NKIVRMYSPVSILDI located
      in p24 Gag subunit. T cells from HIV-1-infected individuals can recognize
      multiple PTE peptide variants, although the magnitude of the responses can vary
      greatly across these variants.

PMID- 27875665
TI  - Eyes on New Product Development.

PMID- 27875666
TI  - Corticosteroid-Induced Psychiatric Symptoms #323.

PMID- 27875664
TI  - Systemic IL-6 Effector Response in Mediating Systemic Bone Loss Following
      Inhalation of Organic Dust.
AB  - Airway and skeletal diseases are prominent among agriculture workers. Repetitive
      inhalant exposures to agriculture organic dust extract (ODE) induces bone
      deterioration in mice; yet the mechanisms responsible for connecting the lung
      bone inflammatory axis remain unclear. We hypothesized that the interleukin (IL)
      6 effector response regulates bone deterioration following inhalant ODE
      exposures. Using an established intranasal inhalation exposure model, wild-type
      (WT) and IL-6 knockout (KO) mice were treated daily with ODE or saline for 3
      weeks. ODE-induced airway neutrophil influx, cytokine/chemokine release, and lung
      pathology were not reduced in IL-6 KO animals compared to WT mice. Utilizing
      micro-computed tomography, analysis of tibia showed that loss of bone mineral
      density, volume, and deterioration of bone micro-architecture, and mechanical
      strength induced by inhalant ODE exposures in WT mice were absent in IL-6 KO
      animals. Compared to saline treatments, bone-resorbing osteoclasts and bone
      marrow osteoclast precursor populations were also increased in ODE-treated WT but
      not IL-6 KO mice. These results show that the systemic IL-6 effector pathway
      mediates bone deterioration induced by repetitive inhalant ODE exposures through
      an effect on osteoclasts, but a positive role for IL-6 in the airway was not
      demonstrated. IL-6 might be an important link in explaining the lung-bone
      inflammatory axis.

PMID- 27875667
TI  - Designing Telemedicine Systems for Geriatric Patients: A Review of the Usability
      Studies.
AB  - BACKGROUND: One area where telemedicine may prove to be highly effective is in
      providing medical care to the geriatric population, an age group predicted to
      account for 20% of the population in the near future. However, even though
      telemedicine has certain advantages, the usability of these systems with this
      population merits investigation. MATERIALS AND METHODS: This article reviews the
      literature published from 2000 to 2016 with the goal of analyzing the
      characteristics of usability-related studies conducted using geriatric
      participants and the subsequent usability challenges identified. Articles were
      found using Web of Knowledge and PubMed citation indexing portals using the
      keywords (1) Telemedicine* AND Geriatrics* (2) Telemedicine* AND Usability* (3)
      Telemedicine* AND Usability* AND Older Adults*. RESULTS: A total of 297 articles
      were obtained from the initial search. After further detailed screening, 16
      articles were selected for review based on the inclusion criteria. Of these, 60%
      of the studies focused on the overall usability of telemedicine systems; 6.25%
      focused on the usability of a telepresence robot; 12.5% compared a face-to-face
      medical consultation with the use of telemedicine systems, and 25% focused on the
      study of other aspects of telemedicine in addition to its usability. Findings
      reported in the studies included high patient satisfaction with telemedicine in
      31.25%, whereas another 31.25% indicated a high acceptance of this method of
      medical consultation. Care coordination in 6.25% of the studies; confidence in
      telemedicine in 6.25%; trust, privacy, and reliability in 6.25%; and increased
      convenience when compared to personal visits in 18.75% were also reported.
      CONCLUSIONS: This review suggests limited research providing scientifically valid
      and reproducible usability evaluation at various stages of telemedicine system
      development. Telemedicine system designers need to consider the age-related
      issues in cognition, perception, and behavior of geriatric patients while
      designing telemedicine applications. Future directions for research were
      developed based on the limitations as well as other results found in this
      systematic review.

PMID- 27875668
TI  - Use of a Perclose ProGlide device for percutaneous endovascular aortic aneurysm
      repair in a general hospital experience.
AB  - BACKGROUND: This study evaluated the safety and efficacy of percutaneous
      endovascular aortic aneurysm repair (EVAR) with a Perclose ProGlide device
      compared with endovascular aortic repair with surgical cutdown of common femoral
      artery in patients at a general hospital. METHODS: A retrospective clinical study
      was conducted using data on 10 patients with elective EVAR, 7 patients with
      percutaneous EVAR, and 9 patients with consecutive rupture abdominal aortic
      aneurysm treated with emergency EVAR from January 2010 to December 2014. RESULTS:
      The median length of intensive care unit stay for elective EVAR, percutaneous
      EVAR, and emergency EVAR cases: 1.80+/-0.92 days, 1.67+/-1.21 days, and 10.00+/
      13.27 days, respectively; hospital days: 11.10+/-4.28 days, 11.00+/-4.10 days,
      and 21.89+/-18.35 days, respectively. Seven patients have no calcification in
      common femoral artery, and the use of a Perclose ProGlide device was under the
      guidance of sonography for percutaneous EVAR. The operative times of elective
      EVAR, percutaneous EVAR, and emergency EVAR were 192.3+/-52.0 minutes, 169.2+/
      67.5 minutes, and 227.1+/-59.9 minutes, and blood loss volumes were 150.0+/-77.5
      ml, 95.0+/-78.6 ml, and 422.2+/-276.3 ml, respectively. Technical success rate of
      Perclose ProGlide was 100%. CONCLUSIONS: Selective percutaneous access of the
      femoral arteries for EVAR is safe and effective in the studied cases. The
      complications can be avoided with careful selection of patients based on
      preoperative imaging. Using Perclose ProGlide for select cases may reduce blood
      loss and operative time.

PMID- 27875669
TI  - Cancer screening of asymptomatic individuals using 18F-FDG PET/CT in China: a
      retrospective study.
AB  - BACKGROUND: In recent years, the application of 18F-fluorodeoxyglucose (FDG)
      positron emission tomography (PET)/computed tomography (CT) for voluntary cancer
      screening of asymptomatic individuals is becoming more and more popular in China.
      However, the utility of such screening is still controversial. METHODS: This
      study enrolled a total of 1,572 asymptomatic individuals who underwent FDG PET/CT
      as a part of cancer screening program in Shanghai Ruijin Hospital, between
      January 2010 and December 2014. Whole set of clinical data of each case was
      retrospectively collected. The cancer detection rate, sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of FDG
      PET/CT were calculated, according to the cancer data obtained from
      histopathological examinations or at least 12-month clinical follow-up. RESULTS:
      Among the 1,572 subjects, malignant tumors were found in 27 cases (1.72%). The
      cancer detection rate was 2.74% among subjects who were older than 50 years,
      4.72% among those who had a family history of malignant tumors, and 2.77% among
      those whose tumor markers were positive. These rates were higher than those among
      other subjects (p<0.05). The detection rate of FDG PET/CT in asymptomatic cancer
      screening was 1.44%, and the sensitivity, specificity, PPV, and NPV were
      estimated to be 85.19%, 99.68%, 82.14%, and 99.75%, respectively. CONCLUSION:
      Considering its less cost-efficient performance, we do not recommend using FDG
      PET/CT for cancer screening in asymptomatic population. Nevertheless, FDG PET/CT
      might be a powerful cancer screening modality with the selection of high-risk
      group, and an optimal combination of the modalities should be provided in order
      to maximize diagnostic performance with lower costs.

PMID- 27875670
TI  - Efficacy of carfilzomib in the treatment of relapsed and (or) refractory multiple
      myeloma: a meta-analysis of data from clinical trials.
AB  - OBJECTIVE: Recently, carfilzomib has become a promising therapeutic approach for
      relapsed and (or) refractory multiple myeloma (RRMM), but no study has summarized
      the overall effect of carfilzomib in RRMM. To explore the role of carfilzomib, we
      performed a meta-analysis of all known prospective clinical trials to assess the
      efficacy of carfilzomib in patients with RRMM. METHODS AND MATERIALS: A
      systematic review of publications was performed on December 15, 2015. Eight
      studies including 1,446 patients were identified. Meta-analyses were carried out
      to calculate the overall response rate (ORR), complete response rate (CRR), and
      clinical benefit rate (CBR) of carfilzomib for RRMM. RESULTS: In patients with
      RRMM, ORR was 0.44, CRR was 0.13, and CBR was 0.54. High heterogeneity between
      studies was observed, and funnel plots were symmetrical, negating publication
      bias. Carfilzomib was generally well tolerated by patients reported in the
      studies though some manageable adverse effects occurred. CONCLUSION: Our analysis
      revealed a promising benefit of carfilzomib in the treatment of RRMM.

PMID- 27875671
TI  - Immune-mediated brain pathology: from autoantibodies to microglia.
AB  - Cells and molecules of the immune system contribute to brain pathology as well as
      to brain homeostasis. We suggest that there are numerous anti-brain antibodies
      that can cause acute neuronal dysfunction if they penetrate brain parenchyma.
      Many of these acute immune-mediated insults may alter the homeostatic mechanisms
      in the brain and initiate pathologic events that no longer depend on the presence
      of the inciting antibody, but rather on microglial cell activation. This
      paradigm, if correct, suggests that there may be two potential moments of
      therapeutic intervention. The first moment is when antibody contacts cells of the
      central nervous system and the second is when microglia become activated and
      impair normal neuronal functions. In this review, we discuss data that support
      this model for immune-mediated pathology in both the adult brain and the
      developing fetal brain.

PMID- 27875672
TI  - Young premenopausal women with breast cancer, especially estrogen receptor
      negative, are at significantly increased risk for subsequent ovarian cancer.
AB  - BACKGROUND: There is a modest risk of second cancers, among them ovarian cancer,
      after breast cancer. For BRCA1 and BRCA2 carriers, the risk increases
      substantially. We have analyzed the risk of ovarian cancer after breast cancer
      based on patient age and the estrogen receptor (ER) and progesterone receptor
      (PR) characteristics of the breast tumor. METHODS: The study population was
      assembled using records from the Surveillance, Epidemiology, and End Results
      (SEER) program of the National Cancer Institute. The SEER program statistical
      analysis software package (SEER*Stat, version 8.2.1) was used to identify
      patients diagnosed with a primary breast cancer from 1990-2010. The SEER*Stat MP
      SIR (Multiple Primary-Standardized Incidence Ratio) tool was used to calculate
      standardized incidence ratios (SIRs) and excess risk for ovarian cancer by
      comparing the patients' subsequent cancer profile to the number of cancers that
      would be expected based on incidence rates for the general U.S. POPULATION: 
      RESULTS: We used data from 316,801 cases of breast cancer. The overall number of
      ovarian cancer cases (n = 288) after ER negative PR negative breast cancer was
      significantly higher than expected (O/E = 1.89, p < 0.05). In premenopausal
      women, that is, women younger than fifty, the ovarian cancer O/E was considerably
      higher than expected. Analysis of latency of ovarian cancer (months) after ER
      negative PR negative breast cancer revealed that in the youngest women the
      latency was shortest (p = 0.001, linear by linear association test for trend).
      CONCLUSION: Young women with pre-menopausal breast cancer, especially ER
      negative, are at significantly increased risk for subsequent ovarian cancer; the
      younger they are, the higher the risk. These women should be routinely tested for
      BRCA1 and BRCA2 mutations, and many might benefit from measures to prevent
      subsequent ovarian cancer.

PMID- 27875673
TI  - Recent advances in engineered T cell therapies targeting B cell malignancies.
AB  - Immunotherapy using engineered autologous T cells has been attempted for decades,
      but clinical trials have only recently demonstrated efficacy. The combination of
      enhanced manufacturing techniques, highly efficient engineering, appropriate
      target selection and synthetic receptors with potent T cell activating domains
      has led to the development of highly-active cellular therapy products. B-cell
      malignancies have served as the paradigmatic diseases to initially evaluate and
      subsequently hone engineered T cells targeting cancer. Two engineered receptors,
      transgenic T cell receptors (tTCRs) and chimeric antigen receptors (CARs), have
      been explored clinically at several different institutions. The most profound
      success has been in pediatric and adult acute lymphoblastic leukemia, in which
      complete response rates after treatment with CD19-directed CAR T cells approach
      90%. Success has been slightly less impressive in slower-growing diseases such as
      chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), and experience
      is much more limited in the plasma cell disease multiple myeloma. A great deal of
      investigation is underway to understand the differences in response rates
      observed, and enhance the efficacy of these therapies in B cell cancers. Here, we
      review landmark and recent clinical trials, as well as pre-clinical work that
      demonstrates significant promise in propelling this field further in the coming
      years.

PMID- 27875675
TI  - Nutrient Intake During Pregnancy.

PMID- 27875674
TI  - Gene therapy approaches for the treatment of retinal disorders.
AB  - There is an impelling need to develop effective therapeutic strategies for
      patients with retinal disorders. Gleaning from the large quantity of information
      gathered over the past two decades on the mechanisms governing degeneration of
      the retina, it is now possible to devise innovative therapies based on retinal
      gene transfer. Different gene-based approaches are under active investigation.
      They include strategies to correct the specific genetic defect in inherited
      retinal diseases, strategies to delay the onset of blindness independently of the
      disease-causing mutations, and strategies to reactivate residual cells at late
      stages of the diseases. In this review, we discuss the status of application of
      these technologies, outlining the future therapeutic potential for many forms of
      retinal blinding diseases.

PMID- 27875676
TI  - Attitudes of European Geneticists Regarding Expanded Carrier Screening.
AB  - OBJECTIVE: To explore attitudes of clinical and molecular geneticists about the
      implementation of multi-disease or expanded carrier screening (ECS) for monogenic
      recessive disorders. DESIGN: Qualitative; semistructured interviews. SETTING: In
      person or via Skype. Interviews were audiorecorded and transcribed verbatim.
      PARTICIPANTS: European clinical and molecular geneticists with expertise in
      carrier screening (N = 16). METHODS: Inductive content analysis was used to
      identify common content categories in the data. RESULTS: Participants recognized
      important benefits of ECS, but they also identified major challenges, including
      limited benefit of ECS for most couples in the general population, lack of
      knowledge on carrier screening among nongenetic health care providers and the
      general public, potential negative implications of ECS for society, and limited
      economic resources. Participants favored an evidence-based approach to the
      implementation of population-wide ECS and were reluctant to actively offer ECS in
      the absence of demonstrable benefits. However, there was a consensus among the
      participants that ECS should be made available to couples who request the test.
      In addition, they believed ECS could be routinely offered to all people who use
      assisted reproduction. CONCLUSION: Although a limited ECS offer is practical, it
      also raises concerns over equality in access to screening. A comprehensive risk
      benefit analysis is needed to determine the desirability of systematic population
      wide ECS.

PMID- 27875677
TI  - A Case Report of Pregnancy During Use of Targeted Therapeutics for Cystic
      Fibrosis.
AB  - New therapeutics, such as ivacaftor, and the combination drug
      lumacaftor/ivacaftor that target the underlying genetic cause of cystic fibrosis
      are being hailed as game-changers in this era of personalized medicine. Although
      these drugs improve lung function, their effects on female fertility have not
      been studied. In this case report we describe one woman's experience with
      ivacaftor and her unanticipated pregnancy. Implications related to comprehensive
      sexual and reproductive health care for women with cystic fibrosis are presented.

PMID- 27875678
TI  - Corrigendum to "Ras nanoclusters: Versatile lipid-based signaling platforms"
      [Biochim. Biophys. Acta 1853/4 (2015) 841-849].

PMID- 27875679
TI  - One Gene, Many Proteins: Mapping Cell-Specific Alternative Splicing in Plants.
AB  - Pre-mRNA alternative splicing (AS) generates protein variants from a single gene
      that can create novel regulatory opportunities. In this issue of Developmental
      Cell, Li et al. (2016) present a high-resolution expression map of AS events in
      Arabidopsis root tissues, giving insight into cell-type- and stage-specific AS
      mechanisms in plants.

PMID- 27875680
TI  - Sumoylation Stabilizes Smoothened to Promote Hedgehog Signaling.
AB  - The conserved Hedgehog signaling pathway is essential for embryonic development
      and tissue homeostasis and is tightly regulated. In this issue of Developmental
      Cell, Ma et al. (2016) demonstrate that sumoylation works in parallel with
      phosphorylation to stabilize Smoothened, antagonizing its ubiquitination and
      subsequent degradation, thus activating Hh target gene transcription.

PMID- 27875681
TI  - Subdistal Appendages Stabilize the Ups and Downs of Ciliary Life.
AB  - Centrioles acquire subdistal appendages (sDAPs) during primary cilium formation.
      In this issue of Developmental Cell, Mazo et al. (2016) demonstrate that sDAPs
      keep cilia submerged within deep membrane invaginations. When sDAPs and
      centrosome cohesion are disrupted, cilia surface to the plasma membrane, which
      may alter mechanical and chemical signal transduction.

PMID- 27875682
TI  - Aging Hematopoietic Stem Cells Make Their History.
AB  - A major hallmark of aging is a decline in tissue regeneration. In a recent issue
      of Cell, Bernitz and colleagues (2016) determine the divisional history of
      hematopoietic stem cells (HSCs) to be a key player of regenerative potential in
      the aging mouse.

PMID- 27875683
TI  - Redox Paradox: Can Hypoxia Heal Ischemic Hearts?
AB  - Adult cardiomyocytes are largely thought to lack proliferative and therefore
      regenerative potential. Reporting in Nature, Nakada et al. (2016) find that a
      hypoxic regime reduces mitochondrial metabolism and promotes proliferation in
      adult mouse cardiomyocytes, resulting in increased regeneration following
      myocardial infarction. These findings suggest the potential to transform post-MI
      care.

PMID- 27875684
TI  - A Tether Is a Tether Is a Tether: Tethering at Membrane Contact Sites.
AB  - Membrane contact sites enable interorganelle communication by positioning
      organelles in close proximity using molecular "tethers." With a growing
      understanding of the importance of contact sites, the hunt for new contact sites
      and their tethers is in full swing. Determining just what is a tether has proven
      challenging. Here, we aim to delineate guidelines that define the prerequisites
      for categorizing a protein as a tether. Setting this gold standard now, while
      groups from different disciplines are beginning to explore membrane contact
      sites, will enable efficient cooperation in the growing field and help to realize
      a great collaborative opportunity to boost its development.

PMID- 27875685
TI  - Progressive disseminated histoplasmosis: a systematic review on the performance
      of non-culture-based diagnostic tests.
AB  - The diagnosis of progressive disseminated histoplasmosis is often a challenge to
      clinicians, especially due to the low sensitivity and long turnaround time of the
      classic diagnostic methods. In recent years, studies involving a variety of non
      culture-based diagnostic tests have been published in the literature. We
      performed a systematic review by selecting studies evaluating non-culture-based
      diagnostic methods for progressive disseminated histoplasmosis. We searched for
      articles evaluating detection of antibody, antigens, as well as DNA-based
      diagnostic methods. A comprehensive PUBMED, Web of Science, and Cochrane Library
      search was performed between the years 1956 and 2016. Case reports, review
      articles, non-human models and series involving less than 10 patients were
      excluded. We found 278 articles and after initial review 18 articles were
      included: (12) involved antigen detection methods, (4) molecular methods, and (2)
      antibody detection methods. Here we demonstrate that the pursuit of new
      technologies is ultimately required for the early and accurate diagnosis of
      disseminated histoplasmosis. In particular, urinary antigen detection was the
      most accurate tool when compared with other diagnostic techniques.

PMID- 27875686
TI  - Early-onset neonatal sepsis and the implementation of group B streptococcus
      prophylaxis in a Brazilian maternity hospital: a descriptive study.
AB  - OBJECTIVES: To describe early-onset neonatal sepsis (EOS) epidemiology in a
      public maternity hospital in Brasilia, Brazil. METHODS: We defined EOS as a
      positive blood culture result obtained from infants aged <=72 hours of life plus
      treatment with antibiotic therapy for >=5 days. Incidence was calculated based on
      the number of cases and total live births (LB). This is a descriptive study
      comparing the period of 2012-2013 with the period of 2014-September 2015, before
      and after implementation of antibiotic prophylaxis during labor for group B
      streptococcus (GBS) prevention, respectively. RESULTS: Overall, 36 infants
      developed EOS among 21,219 LB (1.7 cases per 1000 LB) and 16 died (case fatality
      rate of 44%). From 2014, 305 vaginal-rectal swabs were collected from high-risk
      women and 74 (24%) turned out positive for GBS. After implementation of GBS
      prevention guidelines, no new cases of GBS were detected, and the EOS incidence
      was reduced from 1.9 (95% CI 1.3-2.8) to 1.3 (95% CI 0.7-2.3) cases per 1000 LB
      from 2012-2013 to 2014-September 2015 (p=0.32). CONCLUSIONS: Although the
      reduction of EOS incidence was not significant, GBS colonization among pregnant
      women was high, no cases of neonatal GBS have occurred after implementation of
      prevention guidelines.

PMID- 27875687
TI  - Complete substitution of the Brazilian endemic clone by other methicillin
      resistant Staphylococcus aureus lineages in two public hospitals in Rio de
      Janeiro, Brazil.
AB  - Staphylococcus aureus is an important cause of bloodstream infections. Therefore,
      the main purpose of this work was to characterize a collection of 139 S. aureus
      isolates from bloodstream infections in two public hospitals in relation to their
      antimicrobial susceptibility profile, staphylococcal cassette chromosome mec
      types, and clonal relationship. Methicillin resistance and resistance to other 12
      agents were accessed by the disk diffusion test. Minimum inhibitory concentration
      to mupirocin was also determined. The SCCmec types were accessed by multiplex
      PCR, and the clonal relationship was determined by pulsed field gel
      electrophoresis method and restriction modification system characterization.
      Besides, multilocus sequence typing was performed for representative methicillin
      resistant S. aureus isolates. The military hospital showed a dissemination of the
      New York/Japan (USA100/ST5/CC5/SCCmecII) lineage associated to multidrug
      resistance, including mupirocin resistance, and the teaching hospital presented
      polyclonal and non-multidrug resistant MRSA isolates. Complete substitution of
      the Brazilian endemic clone by other lineages was found in both hospitals. These
      findings can highlight differences in policy control and prevention of infections
      used in the hospitals and a change in the epidemiological profile of MRSA in
      Brazilian hospitals, with the replacement of BEC, a previously well-established
      clone, by other lineages.

PMID- 27875688
TI  - Morphological Identification and Single-Cell Genomics of Marine Diplonemids.
AB  - Recent global surveys of marine biodiversity have revealed that a group of
      organisms known as "marine diplonemids" constitutes one of the most abundant and
      diverse planktonic lineages [1]. Though discovered over a decade ago [2, 3],
      their potential importance was unrecognized, and our knowledge remains restricted
      to a single gene amplified from environmental DNA, the 18S rRNA gene (small
      subunit [SSU]). Here, we use single-cell genomics (SCG) and microscopy to
      characterize ten marine diplonemids, isolated from a range of depths in the
      eastern North Pacific Ocean. Phylogenetic analysis confirms that the isolates
      reflect the entire range of marine diplonemid diversity, and comparisons to
      environmental SSU surveys show that sequences from the isolates range from rare
      to superabundant, including the single most common marine diplonemid known. SCG
      generated a total of ~915 Mbp of assembled sequence across all ten cells and
      ~4,000 protein-coding genes with homologs in the Kyoto Encyclopedia of Genes and
      Genomes (KEGG) orthology database, distributed across categories expected for
      heterotrophic protists. Models of highly conserved genes indicate a high density
      of non-canonical introns, lacking conventional GT-AG splice sites. Mapping
      metagenomic datasets [4] to SCG assemblies reveals virtually no overlap,
      suggesting that nuclear genomic diversity is too great for representative SCG
      data to provide meaningful phylogenetic context to metagenomic datasets. This
      work provides an entry point to the future identification, isolation, and
      cultivation of these elusive yet ecologically important cells. The high density
      of nonconventional introns, however, also portends difficulty in generating
      accurate gene models and highlights the need for the establishment of stable
      cultures and transcriptomic analyses.

PMID- 27875689
TI  - Extreme Diversity of Diplonemid Eukaryotes in the Ocean.
AB  - The world's oceans represent by far the largest biome, with great importance for
      the global ecosystem [1-4]. The vast majority of ocean biomass and biodiversity
      is composed of microscopic plankton. Recent results from the Tara Oceans
      metabarcoding study revealed that a significant part of the plankton in the upper
      sunlit layer of the ocean is represented by an understudied group of
      heterotrophic excavate flagellates called diplonemids [5, 6]. We have analyzed
      the diversity and distribution patterns of diplonemid populations on the extended
      set of Tara Oceans V9 18S rDNA metabarcodes amplified from 850 size- fractionated
      plankton communities sampled across 123 globally distributed locations, for the
      first time also including samples from the mesopelagic zone, which spans the
      depth from about 200 to 1,000 meters. Diplonemids separate into four major
      clades, with the vast majority falling into the deep-sea pelagic diplonemid
      clade. Remarkably, diversity of this clade inferred from metabarcoding data
      surpasses even that of dinoflagellates, metazoans, and rhizarians, qualifying
      diplonemids as possibly the most diverse group of marine planktonic eukaryotes.
      Diplonemids display strong vertical separation between the photic and mesopelagic
      layers, with the majority of their relative abundance and diversity occurring in
      deeper waters. Globally, diplonemids display no apparent biogeographic
      structuring, with a few hyperabundant cosmopolitan operational taxonomic units
      (OTUs) dominating their communities. Our results suggest that the planktonic
      diplonemids are among the key heterotrophic players in the largest ecosystem of
      our biosphere, yet their roles in this ecosystem remain unknown.

PMID- 27875690
TI  - House sparrows.
AB  - Shinichi Nakagawa and Joel Pick introduce what we can learn from house sparrows.

PMID- 27875691
TI  - Traffic noise drowns out great tit alarm calls.
AB  - Anthropogenic noise is one of the fastest growing and most ubiquitous types of
      environmental pollution and can impair acoustic communication in a variety of
      animals [1]. Recent research has shown that birds can adjust acoustic parameters
      of their sexual signals (songs) in noisy environments [2,3], yet we know little
      about other types of vocalizations. Anti-predator signals contain subtle
      information that is critical for avoiding predation [4,5], and failure to detect
      these calls [6,7] as a result of anthropogenic noise pollution could have large
      fitness consequences by negatively impacting survival. We investigated whether
      traffic noise impacts both the production and perception of avian alarm calls
      using a combination of lab and field experiments with great tits (Parus major), a
      songbird that frequently inhabits noise-polluted environments. In response to
      experimental noise manipulation in controlled laboratory conditions, great tits
      increased the amplitude, but not the frequency parameters, of their mobbing alarm
      calls (hereafter 'alarm calls'). Playback experiments conducted in the wild
      indicate that current levels of road traffic noise mask alarm calls, impeding the
      ability of great tits to perceive these critical signals. These results show
      that, despite the vocal adjustments used to compensate for anthropogenic noise,
      great tits are not able to restore the active space of their calls in even
      moderately noisy environments. Consequently, birds are likely to suffer from
      increased predation risk under noise, with likely effects on their behaviour,
      populations, and community dynamics in noise-polluted areas.

PMID- 27875692
TI  - Cognitive control of heart rate in diving harbor porpoises.
AB  - Marine mammals have adapted to forage while holding their breath in a suite of
      aquatic habitats from shallow rivers to deep oceans. The key to tolerate such
      extensive apnea is the dive response, which comprises bradycardia and peripheral
      vasoconstriction. Although initially considered an all-or-nothing reflex [1],
      numerous studies on freely diving marine mammals have revealed substantial
      dynamics of the dive response to meet the impending dive demands of depth,
      duration and exercise [2]. Such adjustments are not only autonomic responses, but
      are under acute cognitive control in pinnipeds [3] living amphibiously on land
      and in water. The fully aquatic cetaceans would similarly benefit from cognitive
      cardiovascular control; however, even though they have exercise-modulated diving
      bradycardia [2] and full voluntary control of their respiratory system to such
      extent that even mild anesthesia often leads to asphyxiation [4], cognitive
      cardiovascular control has never been demonstrated for this large group of marine
      mammals. To address this, we tested the hypothesis that porpoises modulate
      bradycardia according to anticipated dive duration. Two harbor porpoises,
      instrumented with ECG recording tags, were trained to perform 20- and 80-second
      stationary dives, during which they adjusted bradycardia to the anticipated
      duration, demonstrating cognitive control of their dive response.

PMID- 27875693
TI  - Decision Making: A Role for the Amygdala in Translating Goals into Choices.
AB  - A new fMRI study shows that the human amygdala is involved in goal-directed
      planning, further finding that amygdala activation during planning is predictive
      of someone's willingness to forgo immediate small rewards in favor of delayed
      larger rewards.

PMID- 27875694
TI  - Camouflage: Being Invisible in the Open Ocean.
AB  - Animals inhabiting the open ocean often conceal themselves by being highly
      transparent, but this transparency is compromised by light that is scattered and
      reflected from the body surface. New research shows that some midwater
      crustaceans use antireflection coatings to enhance their invisibility.

PMID- 27875695
TI  - Microbial Evolution: Xenology (Apparently) Trumps Paralogy.
AB  - Within-genome gene duplication is generally considered the source of extra copies
      when higher dosage is required and a starting point for evolution of new
      function. A new study suggests that horizontal gene transfer can appear to play
      both roles.

PMID- 27875696
TI  - Visual Neuroscience: Seeing Causality with the Motor System?
AB  - Understanding how humans perceive cause and effect in visual events has long
      intrigued philosophers and scientists. A new study in primates reveals the neural
      correlates of perceived causality at the single-cell level, but in an unexpected
      place - the motor system.

PMID- 27875697
TI  - Sensory Development: Brief Visual Deprivation Alters Audiovisual Interactions.
AB  - Two recent studies have independently demonstrated that short periods of visual
      deprivation early in human development can have long-term functional consequences
      on sensory perception and on the balance between auditory and visual attention.

PMID- 27875698
TI  - Behavioral Neuroscience: Who's Afraid of the C57BL/6 Mouse?
AB  - Behavioral paradigms in which laboratory rodents express behaviors that their
      wild counterparts presumably need every day are rare: a novel prey-capture model
      for laboratory mice has been developed for examining the neurophysiological
      underpinnings of prey capture in mice.

PMID- 27875699
TI  - Evolution: When Dinosaurs Bested Their Early Rivals.
AB  - A sublime fossil discovery in Brazil shows that dinosaurs and their immediate
      evolutionary precursors lived together for tens of millions of years before
      dinosaurs ultimately rose to the top.

PMID- 27875700
TI  - Metacognition: Pre-verbal Infants Adapt Their Behaviour to Their Knowledge
      States.
AB  - Metacognitive abilities, such as knowing we know something or that we made the
      wrong decision, can be powerful tools for adapting behaviour and accelerating
      learning. Apes, dolphins, and even rats demonstrate some such abilities; a new
      study provides evidence that human infants can too.

PMID- 27875701
TI  - Genetics: From Molecule to Society.
AB  - A genome-wide association study of neighborhood characteristics and family income
      finds heritability, identifies single nucleotide polymorphisms and shows genetic
      correlates of these traits with numerous other health and cognitive traits.
      Different mechanisms behind genetic correlations imply different interpretations
      of association and causality.

PMID- 27875702
TI  - Revisiting Neuronal Cell Type Classification in Caenorhabditis elegans.
AB  - We revisit the classification of neuronal cell types in the nervous system of the
      nematode Caenorhabditis elegans. Based on anatomy and synaptic connectivity
      patterns, the 302 neurons of the nervous system of the hermaphrodite were
      categorized into 118 neuron classes more than 30 years ago. Analysis of all
      presently available neuronal gene expression patterns reveals a remarkable
      congruence of anatomical and molecular classification and further suggests
      subclassification schemes. Transcription factor expression profiles alone are
      sufficient to uniquely classify more than 90% of all neuron classes in the C.
      elegans nervous system. Neuron classification in C. elegans may be paradigmatic
      for neuron classification schemes in vertebrate nervous systems.

PMID- 27875703
TI  - Prevalence and characterization of neonatal skin disorders in the first 72h of
      life.
AB  - OBJECTIVE: To determine the prevalence of neonatal dermatological findings and
      analyze whether there is an association between these findings and neonatal and
      pregnancy characteristics and seasonality. METHODS: Newborns from three maternity
      hospitals in a Brazilian capital city were randomly selected to undergo
      dermatological assessment by dermatologists. RESULTS: 2938 neonates aged up to
      three days of life were randomly selected, of whom 309 were excluded due to
      Intensive Care Unit admission. Of the 2530 assessed neonates, 49.6% were
      Caucasians, 50.5% were males, 57.6% were born by vaginal delivery, and 92.5% of
      the mothers received prenatal care. Some dermatological finding was observed in
      95.8% of neonates; of these, 88.6% had transient neonatal skin conditions, 42.6%
      had congenital birthmarks, 26.8% had some benign neonatal pustulosis, 2% had
      lesions secondary to trauma (including scratches), 0.5% had skin malformations,
      and 0.1% had an infectious disease. The most prevalent dermatological findings
      were: lanugo, which was observed in 38.9% of the newborns, sebaceous hyperplasia
      (35%), dermal melanocytosis (24.61%), skin desquamation (23.3%), erythema toxicum
      neonatorum (23%), salmon patch (20.4%), skin erythema (19%), genital
      hyperpigmentation (18.4%), eyelid edema (17.4%), milia (17.3%), genital
      hypertrophy (12%), and skin xerosis (10.9%). CONCLUSIONS: Dermatological findings
      are frequent during the first days of life and some of them characterize the
      newborn's skin. Mixed-race newborns and those whose mothers had some gestational
      risk factor had more dermatological findings. The gestational age, newborn's
      ethnicity, gender, Apgar at the first and fifth minutes of life, type of
      delivery, and seasonality influenced the presence of specific neonatal
      dermatological findings.

PMID- 27875704
TI  - Evaluation of Stress Response During Mesiodens Extraction Under General
      Anesthesia Using Heart Rate Variability.
AB  - PURPOSE: Stress related to dental treatment can be associated with negative
      outcomes. Heart rate variability (HRV) is an objective measurement of autonomic
      nervous system activity. Therefore, HRV was used to identify autonomic nervous
      system reactions during mesiodens extraction under general anesthesia in
      children. MATERIALS AND METHODS: Electrocardiography was performed with
      customized software during treatment. HRV parameters were analyzed according to
      time and frequency domains during each dental procedure (local anesthesia,
      incision, flap, bone removal, extraction of mesiodens, and suturing). The
      relations of HRV parameters to age also were determined. RESULTS: Total autonomic
      nervous system activity decreased markedly after local anesthesia injection.
      Depending on the responses of sympathetic nerve activity, patients were
      categorized in a stress group and a nonstress group. The ratio of low-frequency
      power (LF) to high-frequency power (HF), an indication of sympathetic and
      parasympathetic balance, increased in the stress group after incision and flap
      formation. Conversely, the LF/HF ratio decreased during treatment in the
      nonstress group. However, HR, widely used to evaluate stress responses, did not
      change statistically during mesiodens extraction in either group. HRV parameters
      did not differ statistically according to age. CONCLUSIONS: The internal stress
      related to mesiodens extraction can be evaluated more objectively with HRV
      parameters than with conventional methods. Sympathetic nerve activity in the
      stress group differed from that in the nonstress group during the treatment
      procedures.

PMID- 27875705
TI  - Societal Preference for Gender of Surgeons Performing Patients' Surgery.
AB  - PURPOSE: Previous studies have shown that there may be a bias among some male
      oral and maxillofacial surgeons regarding women practicing in the specialty. The
      purpose of this study was to determine if there is a similar bias in the general
      public. PATIENTS AND METHODS: We performed a survey of 65 patients of various
      genders, educational levels, and ages asking them their surgeon gender preference
      for extraction of a tooth, removal of impacted third molars, and cosmetic
      surgery, as well as the reasons for their preference. RESULTS: Of respondents,
      91% had no preference regarding surgeon gender for tooth extraction, 88% for
      removal of impacted teeth, and 83% for cosmetic surgery. There was no difference
      in gender preference based on the respondents' gender, educational level, or age.
      CONCLUSIONS: There does not appear to be a gender bias against female oral and
      maxillofacial surgeons in the general population.

PMID- 27875706
TI  - Filariasis in Mandible and Maxilla: A Rare Entity-First Report of a Case.
AB  - Wuchereria bancrofti, Brugia malayi, and Brugia timori, categorized as nematodes,
      are responsible for causing lymphatic filariasis. Even though it can affect
      individuals of all age groups and both genders, it predominantly affects people
      of low socioeconomic strata. The filarial worms dwell in the subcutaneous tissues
      and lymphatics of human hosts. In India, W bancrofti is the primary nematode to
      cause filariasis, which is transmitted through the bite of blood-sucking infected
      female anopheles mosquitoes. Lymphangitis, leading to elephantiasis of the legs,
      arms, scrotum, and breast, is the most salient clinical feature of lymphatic
      filariasis. The presence of filarial worms in the oral and perioral soft tissues
      is uncommon; moreover, the presence of filarial worms in a centrally occurring
      bony lesion is highly unusual and has not yet been reported. We report a case of
      a central giant cell granuloma due to filariasis that was diagnosed after biopsy
      of innocuous radiolucent bony lesions of the maxilla and mandible.

PMID- 27875707
TI  - Mucormycosis Causing Ludwig Angina: A Unique Presentation.
AB  - Mucormycosis is a rare fungal infection with a yearly incidence of 1.7 cases per
      million in the United States. It usually occurs in patients with metabolic
      abnormalities or who are immunocompromised with prolonged neutropenia. However,
      it can also occur in patients without any underlying disease process. The
      treatment of choice is surgical debridement of necrotic tissue and systemic
      antifungal therapy, including amphotericin B. A dilemma for the surgeon when
      faced with head and neck mucormycosis is the morbidity of surgical debridement
      from both a functional and cosmetic standpoint. There have been multiple case
      reports of a form of cutaneous mucormycosis in the head and neck involving the
      oral mucosa and the mandible, but no reports in the literature of a fungal
      infection causing Ludwig angina. This report describes one such case. The morbid
      clinical implications of mucormycosis causing Ludwig angina become apparent when
      considering the defect caused by adequate surgical debridement.

PMID- 27875708
TI  - Does Restriction of Public Health Care Dental Benefits Affect the Volume,
      Severity, or Cost of Dental-Related Hospital Visits?
AB  - PURPOSE: On July 1, 2012, the Illinois legislature passed the Save Medicaid
      Access and Resources Together (SMART) Act, which restricts adult public dental
      insurance coverage to emergency-only treatment. The purpose of this study was to
      measure the effect of this restriction on the volume, severity, and treatment
      costs of odontogenic infections in an urban hospital. MATERIALS AND METHODS: A
      retrospective cohort study of patients presenting for odontogenic pain or
      infection at the University of Illinois Hospital was performed. Data were
      collected using related International Classification of Diseases, Ninth Revision
      codes from January 1, 2011 through December 31, 2013 and divided into 2 cohorts
      over consecutive 18-month periods. Outcome variables included age, gender,
      insurance status, oral and maxillofacial surgery (OMS) consultation, imaging,
      treatment, treatment location, number of hospital admission days, and inpatient
      care level. Severity was determined by the presence of OMS consultation, incision
      and drainage, hospital admission, and cost per encounter. Hospital charges were
      used to compare the cost of care between cohorts. Between-patients statistics
      were used to compare risk factors and outcomes between cohorts. RESULTS: Of 5,192
      encounters identified, 1,405 met the inclusion criteria. There were no
      significant differences between cohorts for age (P = .28) or gender (P = .43).
      After passage of the SMART Act, emergency department visits increased 48%,
      surgical intervention increased 100%, and hospital admission days increased 128%.
      Patients were more likely to have an OMS consult (odds ratio [OR] = 1.42; 95%
      confidence interval [CI], 1.11-1.81), an incision and drainage (OR = 1.48; 95%
      CI, 1.13-1.94), and a longer hospital admission (P = .04). The average cost per
      encounter increased by 20% and the total cost of care increased by $1.6 million.
      CONCLUSION: After limitation of dental benefits, there was an increase in the
      volume and severity of odontogenic infections. In addition, there was an
      escalated health care cost. The negative public health effects and increased
      economic impact of eliminating basic dental care show the importance of
      affordable and accessible preventative oral health care.

PMID- 27875709
TI  - Iodine-125 Interstitial Brachytherapy for Pediatric Desmoid-Type Fibromatosis of
      the Head and Neck: A Case Report.
AB  - Desmoid-type fibromatosis (DF) is a locally aggressive benign soft tissue tumor.
      It is rarely observed in the head and neck region and is particularly uncommon in
      the parotid gland. This report describes the case of a 32-month-old girl with DF
      of the head and neck. The tumor was resected with gross residual tumors.
      Recurrence occurred 3 months later and then the patient was treated with iodine
      125 interstitial brachytherapy. The tumor was completely absent 6 months after
      brachytherapy. No recurrence was found 60 months after brachytherapy during
      follow-up. No severe toxicities or growth abnormalities were observed. Very-low
      dose rate brachytherapy as the sole modality could be a reasonable alternative
      for the treatment of inoperable DF of the head and neck, which avoids the risk of
      cosmetic deformity caused by surgery, especially in pediatric patients. In
      addition, long-term follow-up is recommended.

PMID- 27875710
TI  - Vascularized Fascia Lata for Prevention of Postoperative Parotid Fistula Arising
      From Partial Parotidectomy During Neck Dissection.
AB  - PURPOSE: Postoperative parotid fistula can occur after partial parotidectomy,
      which is a routine surgical procedure during neck dissection of oral cancers
      arising from or close to the oropharyngeal area. The aim of this study was to
      evaluate the reliability of vascularized fascia lata for the prevention of
      postoperative parotid fistula after neck dissection. MATERIALS AND METHODS: A
      retrospective review was conducted of patients with oral cancer who underwent
      ablative resection involving the parotid tail and reconstruction using the
      anterolateral thigh (ALT) flap with a vascularized fascia lata paddle. The
      vascularized fascia lata paddle was used to seal off the parotid stump by tightly
      suturing the edges of the fascia lata and parotid wound together. RESULTS: Twenty
      three patients (18 men and 5 women) with primary oral cancer arising from or
      close to the oropharyngeal area were enrolled. The mean area of parotid defect
      was 16.7 cm2 and the mean area of fascia lata harvested was 21.8 cm2. All flaps
      survived. Pressure dressing or anticholinergic drugs were not used in any case.
      During the follow-up period, there was no clinical evidence of the development of
      parotid fistula. CONCLUSION: The vascularized fascia lata paddle is a reliable
      option for the prevention of postoperative parotid fistula after neck dissection
      of oral cancer.

PMID- 27875711
TI  - Corrigendum to "External conditions inversely change the RNA polymerase II
      elongation rate and density in yeast" [Biochim. Biophys. Acta 1829/11 (2013) 1248
      1255].

PMID- 27875712
TI  - Urinary phthalate and phthalate alternative metabolites and isoprostane among
      couples undergoing fertility treatment.
AB  - BACKGROUND: Epidemiological data suggest associations between phthalate exposures
      to a variety of adverse reproductive outcomes including reduced sperm quality and
      reproductive success. While mechanisms of these associations are not fully
      elucidated, oxidative stress has been implicated as a potential mediator. We
      examined associations of urinary metabolites of phthalates and phthalate
      alternative plasticizers with oxidative stress among couples seeking fertility
      treatment. METHODS: Seventeen urinary plasticizer metabolites and 15-F2t
      isoprostane, a biomarker of oxidative stress, were quantified in spot samples
      from 50 couples seeking fertility treatment who enrolled in the Sperm
      Environmental Epigenetics and Development Study during 2014-2015. RESULTS: In
      multivariable analyses, percent change in isoprostane was positively associated
      with interquartile range increases for the oxidative metabolites of di-2
      ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%,
      p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2
      ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate
      (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003),
      and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%,
      p=0.002). Stratification of participants by sex revealed that isoprostane was
      positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl
      phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP
      (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males.
      CONCLUSIONS: Our results suggest that exposure to phthalates and phthalate
      replacements are associated with higher levels of oxidative stress in a sex
      specific manner. Additional studies are needed to replicate our findings and to
      examine the potential health implications of the use of phthalates and
      alternative phthalates in consumer end products.

PMID- 27875713
TI  - Prognostic value of degree and types of anaemia on clinical outcomes for
      hospitalised older patients.
AB  - STUDY OBJECTIVE: This study investigated in a large sample of in-patients the
      impact of mild-moderate-severe anaemia on clinical outcomes such as in-hospital
      mortality, re-admission, and death within three months after discharge. METHODS:
      A prospective multicentre observational study, involving older people admitted to
      87 internal medicine and geriatric wards, was done in Italy between 2010 and
      2012. The main clinical/laboratory data were obtained on admission and discharge.
      Based on haemoglobin (Hb), subjects were classified in three groups: group 1 with
      normal Hb, (reference group), group 2 with mildly reduced Hb (10.0-11.9g/dL in
      women; 10.0-12.9g/dL in men) and group 3 with moderately-severely reduced Hb
      (<10g/dL in women and men). RESULTS: Patients (2678; mean age 79.2+/-7.4y) with
      anaemia (54.7%) were older, with greater functional impairment and more
      comorbidity. Multivariable analysis showed that mild but not moderate-severe
      anaemia was associated with a higher risk of hospital re-admission within three
      months (group 2: OR=1.62; 95%CI 1.21-2.17). Anaemia failed to predict in-hospital
      mortality, while a higher risk of dying within three months was associated with
      the degree of Hb reduction on admission (group 2: OR=1.82;95%CI 1.25-2.67; group
      3: OR=2.78;95%CI 1.82-4.26) and discharge (group 2: OR=2.37;95%CI 1.48-3.93;
      group 3: OR=3.70;95%CI 2.14-6.52). Normocytic and macrocytic, but not microcytic
      anaemia, were associated with adverse clinical outcomes. CONCLUSIONS: Mild
      anaemia predicted hospital re-admission of older in-patients, while three-month
      mortality risk increased proportionally with anaemia severity. Type and severity
      of anaemia affected hospital re-admission and mortality, the worst prognosis
      being associated with normocytic and macrocytic anaemia.

PMID- 27875714
TI  - The role of ego-resiliency in the relationship between social anxiety and problem
      solving ability among South Korean nursing students.
AB  - BACKGROUND: Problem-solving is a core ability that nursing students should
      develop during their education. There is a need to better understand the
      importance of problem-solving and the factors related to it among nursing
      students. OBJECTIVES: This study aimed to identify the role of ego-resiliency in
      the relationship between social anxiety and problem-solving ability in Korean
      nursing students. METHODS: Data were collected from a total of 329 nursing
      students who were enrolled in three nursing programs in South Korea, using a self
      administrated questionnaire. Data were mainly analyzed by Baron and Kenny's three
      step regression analysis and the Sobel test. RESULTS: Ego-resiliency played a
      partial mediating role in the relationship between social anxiety and problem
      solving ability. Further, the Sobel test suggested a mediating effect of ego
      resiliency on the relationship between social anxiety and problem-solving (Z=
      9.079, p<0.001). CONCLUSIONS: To enhance problem-solving ability in nursing
      students, nursing educators should establish educational strategies that decrease
      social anxiety and improve ego-resiliency.

PMID- 27875715
TI  - Common and divergent neural correlates of anomia in amnestic and logopenic
      presentations of Alzheimer's disease.
AB  - The majority of logopenic variant primary progressive aphasia (lv-PPA) cases
      harbour Alzheimer pathology, suggesting that lv-PPA constitutes an atypical
      presentation of Alzheimer's disease (AD). However, even if caused by Alzheimer
      pathology, the clinical manifestations of lv-PPA differ from those observed in
      the typical or amnestic AD presentation: in lv-PPA, aphasia is the main feature
      while amnestic AD is characterised by impaired episodic memory. Anomia or
      impaired naming, however, is present in both AD presentations. Whether these
      presentations share anatomical and mechanistic processes of anomia has not been
      fully investigated. Accordingly, we studied naming performance and its
      relationship with regions of brain atrophy in 23 amnestic AD and 22 lv-PPA cases
      with presumed underlying Alzheimer pathology. Both AD groups displayed some
      degree of anomia and impaired word comprehension but these were particularly
      severe in lv-PPA and accompanied by a range of linguistic deficits, comprising
      phonological substitutions, superordinate semantic paraphasias and abnormal
      single-word repetition. Analysis of cortical thickness revealed that anomia was
      correlated with thinning in left superior temporal gyrus in both groups. In
      amnestic AD, however, anomia was also associated with thinning in right inferior
      temporal regions. Single-word comprehension (SWC), by contrast, was associated
      with cortical thinning involving bilateral fusiform gyri in both groups. These
      findings suggest that anomia in both amnestic AD and lv-PPA results from the
      involvement at multiple steps of word processing, in particular, semantic and
      lexical retrieval; in addition lv-PPA patients display a more marked involvement
      of phonological processing.

PMID- 27875716
TI  - Face identity is encoded in the duration of N170 adaptation.
AB  - Previous studies assessing the involvement of the face-sensitive N170 component
      of the event-related potential (ERP) in the processing of face identity have
      shown controversial results when assessing N170 amplitude in repetition
      suppression (RS) designs. On the other hand, N170 adaptation is robustly
      associated with the inter-stimulus interval (ISI) between immediate face
      repetitions. Interestingly, interactions of face identity and ISI could provide
      valuable information on early encoding of face identity, but have not been
      investigated so far. We employed a repetition suppression paradigm using
      identical and non-identical repetitions as well as parametrically varied ISIs
      between 500 msec and 2,000 msec in 27 healthy subjects to investigate N170
      adaptation effects. Both face identity and varying ISIs significantly influenced
      N170 adaptation effects, albeit with small effects sizes. Most importantly,
      however, face identity and ISIs strongly interacted with rapid N170 amplitude
      recovery in non-identical trials, but sustained N170 adaptation in identical
      trials. We excluded low-level sensory contributions to the N170 adaptation effect
      by analyzing the P1 component and by running an additional experiment employing
      different stimulus sizes. This specific result strongly argues in favor of
      neuronal sensitivity to face identity, which is primarily mirrored in the N170
      temporal decay function that essentially differentiates identical and non
      identical face trials. In general, taking advantage of the temporal dimension of
      adaptation processes, i.e., their decay over time, provides additional
      dissections of neuronal function into feature-specific selectivity versus non
      selectivity.

PMID- 27875717
TI  - Comparative study on the mobility and speciation of heavy metals in ashes from co
      combustion of sewage sludge/dredged sludge and rice husk.
AB  - The co-combustion of sludge (sewage and dredged sludge) with rice husk is
      expected to become a trend because of its economic and environmental benefits.
      However, the massive residues from the co-combustion process and the mobility of
      heavy metals (HMs) warrant special attention. The basic performance and
      environmental properties of the trace elements (Cr, Cu, Fe, Mn, Ba and Zn) from
      the co-combustion ashes were studied to promote the further utilization of these
      materials. These ashes have a shell particle shape, high specific area, high
      amorphous content and low crystalline phase content. The investigation mainly
      focused on the environmental properties of these ashes to evaluate the risk of
      these by-products to the environment. Results show Cu, Mn, and Zn have cumulative
      leaching concentrations of 1.033, 23.32, and 3.363 mg/L for W, by contrast, Cr,
      Cu, Fe, Mn, Ba, and Zn have cumulative leaching concentrations of 0.488, 0.296,
      8.069, 10.44, 2.568, and 2.691 mg/L for H, which are much greater than the
      Chinese ground water standard (GB/T14848-93). Meanwhile Mn, Zn, Ba, Cr, and Fe
      all pose a very high risk for H, while Cu only poses a medium risk, and all HMs
      in W exhibit much lower contamination levels than those in H by the method of
      risk assessment code (RAC). It indicates that these ashes have undesirably high
      levels of HMs that demonstrate high mobility and pose environmental risks
      according to their leachability and chemical speciation. And the HMs in W show
      lower mobility and environmental hazards than those in H.

PMID- 27875718
TI  - An adsorbent with a high adsorption capacity obtained from the cellulose sludge
      of industrial residues.
AB  - One of the major problems in effluent treatment plants of the cellulose and paper
      industry is the large amount of residual sludge generated. Therefore, this
      industry is trying to develop new methods to treat such residues and to use them
      as new products, such as adsorbents. In this regard, the objective of this work
      was to develop an adsorbent using the raw activated sludge generated by the
      cellulose and paper industry. The activated cellulose sludge, after being dried,
      was chemically activated with 42.5% (v/v) phosphoric acid at 85  degrees C for 1
      h and was charred at 500  degrees C, 600  degrees C and 700  degrees C for 2 h.
      The efficiency of the obtained adsorbent materials was evaluated using kinetic
      tests with methylene blue solutions. Using the adsorption kinetics, it was
      verified that the three adsorbents showed the capacity to adsorb dye, and the
      adsorbent obtained at a temperature of 600  degrees C showed the highest
      adsorption capacity of 107.1 mg g-1. The kinetic model that best fit the
      experimental data was pseudo-second order. The Langmuir-Freudlich isotherm
      adequately described the experimental data. As a result, the cellulose sludge
      generated by the cellulose and paper industries could be used as an adsorbent.

PMID- 27875719
TI  - Evaluation of some factors influencing on variability in bioaccumulation of heavy
      metals in rodents species: Rombomys opimus and Rattus norvegicus from central
      Iran.
AB  - In the present study, the effects of sex, age, nutritional status, and habitat
      use on hair and internal tissue concentrations of some trace metals (Zn, Cu, Ni,
      Pb and Cd) in brown rat (Rattus norvegicus) and great gerbil (Rhombomys opimus)
      from Aran-O-Bidgol City in Central Iran were investigated. Five sampling stations
      in different land-uses were selected for the study. Concentrations of Cd and Pb
      in liver and whole body concentration as well as concentration of Zn in hair of
      male rats were significantly higher than females. A significantly higher
      concentration was only observed for Pb in kidney of male gerbils than females. In
      numerous cases, age had significantly negative correlations with concentration of
      metals in different tissues of both species, and was only significantly (and
      positively) correlated with the concentration of Cd in kidney and Zn in liver of
      gerbils. This finding may indicate that the early neonatal age is a critical
      period for metals accumulation. The relationships between nutritional status and
      metal concentrations for both species were negative, which can be ascribed to the
      weight-specific metabolic rate that cause to a relatively low uptake of metals
      per unit of body weight. No significant differences were observed for soil metals
      concentrations in different sites. So, this suggests that the influence of life
      history, microhabitat use and foraging behavior did significantly influence on
      inter and intra specific variation of metals concentration in small mammals. Our
      observations suggest that hair cannot be used alone for monitoring exposure of
      metals.

PMID- 27875720
TI  - Multi-generational xenoestrogenic effects of Perfluoroalkyl acids (PFAAs) mixture
      on Oryzias latipes using a flow-through exposure system.
AB  - To elucidate the multi-generational estrogenic potential of Perfluoroalkyl acids
      (PFAAs) mixture, vitellogenin (VTG) expression, growth indices, histological
      alteration, fecundity, hatching rate, larval survival rate, and sex ratio of
      Japanese medaka (Oryzias latipes) were investigated by exposing the fish to a
      mixture of perfluorooctane sulfonate (PFOS), perfluroroctanoic acid (PFOA),
      perfluorobutane sulfonate (PFBS), and perfluorononanoic acid (PFNA) for three
      generations (238 days). Mixture composition is in the ratio of 1:1:1:1. In
      addition, whole body burden for each PFAA was analyzed. According to the results,
      concentrated levels of the PFAAs in both F1 and F2 generation O. latipes were
      ordered PFOS > PFNA > PFOA > PFBS at both low concentration (0.5 MUg/L) and high
      concentration (5 MUg/L), whereas a significant difference in whole body burden
      based on sex or generation was not detected. Significant induction of VTG
      expression in F2 and the decline of the gonad somatic index (GSI) in F1 were
      observed following PFAAs mixture exposure (p < 0.05, one-way ANOVA). Furthermore,
      suppression level of reproduction rate relative to the control increased as
      generation was transferred to the next in response to PFAAs mixture or 17 beta
      estradiol exposure, with the inhibition of hatchability observed in the F1
      generation. The PFAA high concentration caused significant alteration of F1
      generation sex ratio, suggesting the adverse effect of PFAA in population level
      (Chi-square test, P > 0.05). Overall, this study demonstrated that PFAA mixture
      could have the potential of multi-generational endocrine disruptors in O.
      latipes.

PMID- 27875721
TI  - Percutaneous mitral valve repair: The last chance for symptoms improvement in
      advanced refractory chronic heart failure?
AB  - BACKGROUND: The role of percutaneous mitral valve repair (PMVR) in patients with
      end-stage heart failure (HF) and functional mitral regurgitation (FMR) is
      unclear. METHODS: Seventy-five consecutive patients with FMR grade>=3+ and severe
      HF symptoms despite optimal medical therapy and resynchronization therapy
      underwent PMVR with the MitraClip system (Abbott, Abbott Park, IL, USA) at 3
      centers. Clinical evaluation, echocardiography and pro-BNP measurement were
      performed at baseline and at 6-month. RESULTS: Mean age was 67+/-11years,
      logistic EuroSCORE=23+/-18%, left ventricle ejection fraction (LVEF) 30+/-9%. In
      6 patients (8%) PMVR was performed as a bridge to heart transplant; many patients
      were dependent from iv diuretics and/or inotropes. Rate of serious adverse in
      hospital events was 1.3% (1 patient who died after conversion to cardiac
      surgery). Sixty-three patients (84%) were discharged with MR<=2+. At 6-month, 4
      patients died (5%), 80% had MR<=2+ and 75% were in New York Heart Association
      class <=II. Median pro-BNP decreased from 4395pg/ml to 2594pg/ml (p=0.04). There
      were no significant changes in LV end-diastolic volume (222+/-75ml vs. 217+/-79,
      p=0.19), end-systolic volume (LVESV, 154+/-66ml vs. 156+/-69, p=0.54) and LVEF
      (30+/-9% vs. 30+/-12%, p=0.86). Significant reverse remodeling (reduction of
      LVESV>=10%) was observed in 25%, without apparent association with baseline
      characteristics. The number of hospitalizations for HF in comparison with the
      6months before PMVR were reduced from 1.1+/-0.8 to 0.3+/-0.6 (p<0.001).
      CONCLUSIONS: In extreme risk HF patients with FMR, PMVR improved symptoms and
      reduced re-hospitalization and pro-BNP levels at 6months, despite the lack of LV
      reverse remodeling.

PMID- 27875723
TI  - Orosomucoid as prognosis factor associated with inflammation in acute or
      nutritional status in chronic heart failure.
AB  - BACKGROUND: Inflammation and nutritional state are involved in the pathogenesis
      of heart failure (HF). OBJECTIVE: To study the contribution of alpha-1-acid
      glycoprotein (AGP) to these factors and its prognostic value in acute (AHF) or
      chronic HF (CHF). METHODS: The observational study has included 147 patients
      (mean age 70years, 62% men) admitted to a cardiology department for HF and
      followed-up for an average 326.6+/-140.8days. Blood AGP values were measured by
      Enzyme-Linked ImmunoSorbent Assay. Monocytes subsets were determined with CD14
      and CD16 antibodies by flow cytometry and body composition was measured by dual
      energy X-ray absorptiometry. The regulation of tumor necrosis factor (TNF-alpha)
      and leptin by AGP in epicardial adipose tissue (EAT) were analyzed by real time
      polymerase chain reaction. RESULTS: High AGP, that was associated with CD14+CD16+
      monocytes, and proBNP levels at the discharge were indicators of
      rehospitalization for HF in AHF patients. However, low AGP levels determined a
      worse nutritional state in CHF patients. The leptin levels were downregulated by
      high AGP concentration in epicardial fat. CONCLUSION: AGP is a dual indicator in
      HF because high levels are predictors of adverse outcomes in AHF but low levels
      are related to the worse nutritional status in CHF. The regulation of leptin by
      AGP in epicardial fat might suggest a new pathway as protective mechanism in CHF.

PMID- 27875722
TI  - Progenitor cells from atria, ventricle and peripheral blood of the same patients
      exhibit functional differences associated with cardiac repair.
AB  - AIM: Deciding the best cell type for cardiac regeneration remains a big
      challenge. No studies have directly compared the functional efficacy of cardiac
      progenitor cells (CPCs) with extra-cardiac stem cells isolated from the same
      patient. METHODS AND RESULTS: We compared the functional characteristics of
      endothelial progenitor cells (EPCs), right atrial (RAA) CPCs and left ventricular
      (LV) CPCs isolated from the same patients (n=14). Within the same heart, RAA and
      LV CPCs exhibited marked differences in surface marker expression, with RAA CPCs
      exhibiting better expansion potential and migration properties. When subjected to
      hypoxia and serum starvation to simulate in vivo ischemic environment, RAA and LV
      CPCs exhibited similar pattern of resistance to apoptotic cell death under
      ischemia. Interestingly, EPCs exhibited highest resistance to apoptotic cell
      death, however, they also showed the lowest proliferation under hypoxia. RT
      profiler array showed comparable gene expression pattern in RAA and LV CPCs,
      while they were differentially expressed in EPCs. Further, treating human
      umbilical vein endothelial cells with conditioned medium (CM) from LV showed
      maximum angiogenic potential, while cardiomyocytes treated with CM from RAA
      showed greatest survival under hypoxic conditions. CONCLUSIONS: Results from this
      study provide the first evidence that progenitor cells from different regions
      exhibit functional differences within the same patient.

PMID- 27875724
TI  - The LifeLines Cohort Study: Prevalence and treatment of cardiovascular disease
      and risk factors.
AB  - BACKGROUND: The LifeLines Cohort Study is a large three-generation prospective
      study and Biobank. Recruitment and data collection started in 2006 and follow-up
      is planned for 30years. The central aim of LifeLines is to understand healthy
      ageing in the 21st century. Here, the study design, methods, baseline and major
      cardiovascular phenotypes of the LifeLines Cohort Study are presented. METHODS
      AND RESULTS: Baseline cardiovascular phenotypes were defined in 9700 juvenile (8
      18years) and 152,180 adult (>=18years) participants. Cardiovascular disease (CVD)
      was defined using ICD-10 criteria. At least one cardiovascular risk factor was
      present in 73% of the adult participants. The prevalence, adjusted for the Dutch
      population, was determined for risk factors (hypertension (33%),
      hypercholesterolemia (19%), diabetes (4%), overweight (56%), and current smoking
      (19%)) and CVD (myocardial infarction (1.8%), heart failure (1.0%), and atrial
      fibrillation (1.3%)). Overall CVD prevalence increased with age from 9% in
      participants<65years to 28% in participants>=65years. Of the participants with
      hypertension, hypercholesterolemia and diabetes, respectively 75%, 96% and 41%
      did not receive preventive pharmacotherapy. CONCLUSIONS: The contemporary
      LifeLines Cohort Study provides researchers with unique and novel opportunities
      to study environmental, phenotypic, and genetic risk factors for CVD and is
      expected to improve our knowledge on healthy ageing. In this contemporary Western
      cohort we identified a remarkable high percentage of untreated CVD risk factors
      suggesting that not all opportunities to reduce the CVD burden are utilised.

PMID- 27875726
TI  - The association of uncoupling protein 2 (UCP2) exon 8 insertion/deletion
      polymorphism and ECG derived QRS duration: A cross-sectional study in an
      Australian rural population.
AB  - BACKGROUND: Associations between inherited mitochondrial disease and cardiac
      conduction have been previously described. However, there are no available
      studies exploring the mitochondrial uncoupling protein 2 gene (UCP2)
      insertion/deletion (I/D) polymorphisms interaction on cardiac electrical
      conduction. Our aim was to determine if ECG-derived QRS duration is associated
      with UCP2 DD genotype in a cross-sectional Australian aging rural population.
      METHODS: A retrospective study design utilizing a rural health diabetic screening
      clinic data-base containing observational data from September 2011 to September
      2014. Inclusion criteria included were having ECG parameters such as QRS duration
      measures and a DNA sample within the same subject. Genomic DNA was extracted and
      subjects were genotyped for the 45-bp I/D polymorphism in the 3'-untranslated
      region of UCP2. RESULTS: 281 individuals were available for analysis. On the
      basis of QRS duration >140ms we found an increased percentage of our population
      with DD homozygotes, compared to ID heterozygotes and II homozygotes (p=0.047).
      For other ECG parameters; mean PQ duration, QTc across UCP2 genotypes was not
      significant (p=NS). QTc using a cut-off >440ms in contingency table analysis
      revealed no significant differences across UCP2 I/D genotypes. Mean QT dispersion
      (QTd) was paradoxically less in the UCP2 DD genotype compared to UCP2 II subgroup
      (p=0.034). DISCUSSION: We have demonstrated an association between increasing ECG
      derived QRS duration >140ms and the UCP2 DD polymorphism. The lack of association
      with ECG derived QTd and UCP2 DD may suggest that gene-related QRS duration
      prolongation is independent of cardiac hypertrophy.

PMID- 27875725
TI  - Association of CXCR4 expression with coronary collateralization in patients with
      chronic total coronary occlusion: A nested case-control study.
AB  - OBJECTIVE: CXCR4 signaling contributes to the development and progression of
      neovascularization. The objective of this study was to investigate whether CXCR4
      expression in peripheral CD34+ cells associated with the coronary
      collateralization (CC) in patients with chronic total coronary occlusion (CTO).
      METHODS AND RESULTS: We measured CXCR4 expression in peripheral CD34+ cells and
      assessed its relation with CC in a nested case-control study including 78 cases
      and 78 matched controls aged 38-69years, assessed in January 2011 to December
      2012 and with at least 1year of follow-up before the index date. Cases were
      defined as good coronary collateralization (GCC) according to the Rentrop scoring
      system (Rentrop score of 2 or 3); for each case, one age-matched control with
      poor coronary collateralization (PCC) (Rentrop score 0 or 1) was randomly
      selected from the study participants. Demographic, biochemical, and angiographic
      variables were collected. In multivariate analysis, the OR (95% CI) of CXCR4
      expression was 0.018 (0.017 to 0.020) in patients with GCC versus PCC.
      Independent effect of CXCR4 expression on CC was (OR 0.012, 95% CI 0.010-0.014)
      when adjusted for other variables. A nonlinear relationship between CXCR4
      expression and CC was observed. The CC degree increased when CXCR4 expression
      exceeded the turning point (30%) (OR 0.025, 95% CI 0.022-0.028; p<0.001). When
      the CXCR4 expression exceeded 75%, increased CXCR4 level could not promoted CC
      (OR 0.000, 95% CI 0.008-0.007; p=0.974). CONCLUSION: Increased CXCR4 level in
      peripheral CD34+ cells was associated with GCC in patients with CTO.

PMID- 27875727
TI  - Predictor of left ventricular dysfunction after aortic valve replacement in mixed
      aortic valve disease.
AB  - BACKGROUND: The fate of the left ventricle (LV) after aortic valve replacement
      (AVR) in mixed aortic valve disease (MAVD) is unknown. METHODS: Patients with
      moderate-severe MAVD, ejection fraction >=50%, and no coronary artery disease who
      underwent AVR were identified. Moderate-severe MAVD was defined as a combination
      of >=moderate aortic stenosis and >=moderate aortic regurgitation. Assessment for
      LVD was performed at 1 and 5years after AVR. The purpose of the study was to
      determine prevalence and predictors of early and late left ventricular
      dysfunction (LVD) defined as ejection fraction <50% at 1 and 5years post-AVR. The
      severity of LV hypertrophy was assessed using LV mass index (LVMI), while
      relative wall thickness (RWT) was used to determine the type of hypertrophy. RWT
      was calculated as (2*posterior wall thickness)/LV end-diastolic dimension
      (LVEDD). A RWT score >=0.42 and <0.42 indicates concentric and eccentric
      hypertrophy respectively. RESULTS: Patients with MAVD (n=179); age 63+/-8years,
      males 134 (75%); underwent AVR at Mayo Clinic, 1994-2010. Early LVD occurred in
      38(21%). Predictors of early LVD were LVMI/LVEDD >3.1 (HR 1.83, CI 1.59-1.98);
      RWT >0.46 (HR 2.16, CI 1.21-4.99); and older age (HR 1.62, CI 1.23-3.02).
      Assessment of LV function was performed in 124 patients at 5-years post-AVR, and
      late LVD was present in 29(23%). Predictors of late LVD were LVMI/LVEDD >3.1 (HR
      1.77, CI 1.24-2.01) and RWT >0.46 (HR 1.65, CI 1.29-2.24). All-cause mortality
      occurred in 21(12%), and was more common in patients with LVMI/LVEDD >3.1
      (P=0.043) and RWT >0.46 (P=0.029). Patients with postoperative LVD showed less
      regression of LV mass after AVR even after controlling for blood pressure.
      CONCLUSIONS: LVD can occur after AVR even in the setting of normal preoperative
      LV function and absence of coronary artery disease. Preoperative LV mass was
      predictive of LVD and should be taken into consideration when determining the
      timing of AVR.

PMID- 27875728
TI  - Exercise-induced pulmonary hypertension by stress echocardiography: Prevalence
      and correlation with right heart hemodynamics.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence of exercise
      induced pulmonary hypertension (EIPH) in consecutive subjects referred for stress
      echocardiography for chest pain or shortness of breath and correlate
      echocardiographic diagnosis of EIPH with hemodynamics at right heart
      catheterization (RHC). BACKGROUND: Elevated pulmonary pressure can lead to
      significant morbidity and mortality. EIPH by ehocardiography has been described
      in patients with connective tissue disease. It's prevalence in the setting of
      routine clinically indicated stress echocardiography unknown. METHODS: In a
      retrospective analysis of 4068 consecutive stress subjects undergoing stress
      echocardiography, 479 subjects with EIPH were identified. All 479 subjects with
      EIPH were compared to 479 age and sex matched subjects with normal pulmonary
      artery pressures post exercise. EIPH was defined as PASP>50mmHg or peak tricuspid
      regurgitation velocity>3.2m/s. Of 100 patients with EIPH who underwent RHC we
      identified variables which predicted abnormal hemodynamic findings on RHC.
      RESULTS: The prevalence of EIPH in subjects referred for stress echocardiography
      was 11.7%. A greater proportion of subjects with EIPH were obese or had lung
      disease or connective tissue disease. Of 100 subjects who underwent RHC, 65 had
      abnormal results. Age>55years (OR 5.1, p<0.01]) or dilated left atrium (OR 4.4,
      p=0.02]) were independently associated with abnormal right heart hemodynamics.
      CONCLUSIONS: The results demonstrate that 11.7% of patients undergoing clinically
      indicated stress echocardiography have EIPH. Of those who underwent RHC abnormal
      hemodynamics were significantly associated with a dilated left atrium or age
      older than 55years.

PMID- 27875729
TI  - "Seesaw balloon-wire cutting" technique is superior to Tornus catheter in balloon
      uncrossable chronic total occlusions.
AB  - BACKGROUND: Inability to advance a balloon is a well-recognized cause leading to
      a failure in recanalization of chronic total occlusions (CTOs) despite
      successfully passing a guidewire. A few techniques and devices have been
      introduced to facilitate balloon passage, especially the use of Tornus catheter.
      However, complex manipulation, expensive cost, and availability limit the
      application of these methods. This study was to evaluate the efficiency and
      safety of "seesaw balloon-wire cutting" technique in comparison with Tornus
      catheter for balloon uncrossable CTOs. METHODS: Eighty patients with balloon
      uncrossable CTOs were enrolled in this study. Among them, 40 patients treated
      with "seesaw balloon-wire cutting" technique were consecutively investigated and
      40 patients treated with Tornus catheter before were matched retrospectively. A
      rotablator or retrograde strategy was taken as a bail-out strategy. Success rates
      of device and procedure and complication rate were assessed. Complications
      included coronary dissection, cardiac tamponade, death, Q-wave myocardial
      infarction (MI), non-Q-wave MI, emergency PCI and bypass surgery. RESULTS:
      Compared with the Tornus catheter, device success rate was significantly higher
      with the "seesaw balloon-wire cutting" technique (87.5% vs. 45.0%, P<0.001), and
      the mean procedural time was much shorter (90.5+/-8.3min vs. 141.5+/-21.3min,
      P<0.001). The procedural success rate was also higher with the "seesaw balloon
      wire cutting" technique (92.5% vs.72.5%, P=0.037). There were no differences in
      complication rate. CONCLUSION: The "seesaw balloon-wire cutting" technique is
      superior to the Tornus catheter in treating balloon uncrossable CTOs.

PMID- 27875730
TI  - Contemporary review on the pathogenesis of takotsubo syndrome: The heart shedding
      tears: Norepinephrine churn and foam at the cardiac sympathetic nerve terminals.
AB  - Takotsubo syndrome (TS), an increasingly recognized acute cardiac disease entity,
      is characterized by a unique pattern of circumferential and typically regional
      left ventricular wall motion abnormality resulting in a conspicuous transient
      ballooning of the left ventricle during systole. The mechanism of the disease
      remains elusive. However, the sudden onset of acute myocardial stunning in a
      systematic pattern extending beyond a coronary artery territory; the history of a
      preceding emotional or physical stress factor in two thirds of cases; the signs
      of sympathetic denervation at the regions of left ventricular dysfunction on
      sympathetic scintigraphy; the finding of myocardial edema and other signs
      consistent with (catecholamine-induced) myocarditis shown by cardiac magnetic
      resonance imaging; and the contraction band necrosis on histopathological
      examination all argue strongly for the involvement of the cardiac sympathetic
      nervous system in the pathogenesis of TS. In this narrative review, extensive
      evidence in support of local cardiac sympathetic nerve hyperactivation,
      disruption and norepinephrine spillover causing TS in predisposed patients is
      provided.

PMID- 27875731
TI  - A study of the short-term associations between hospital admissions and mortality
      from heart failure and meteorological variables in Hong Kong: Weather and heart
      failure in Hong Kong.
AB  - BACKGROUND: Previous research has shown winter peaks for both hospitalizations
      and mortality from HF, but few studies have examined the association between
      meteorological parameters and HF. METHODS: Daily HF admissions to Hong Kong
      public hospitals, which cover about 83% of total admissions, and daily HF deaths,
      were obtained for 2002-2011. Generalized additive (Poisson) regression models
      were used with daily HF admissions/mortality as outcomes and daily mean
      temperature, humidity, and wind speed as predictors, while controlling for
      pollutant levels, time trend, season, day of the week, and holiday. Non-linear
      distributed lag functions were used for predictors to allow for non-linear and
      delayed associations. RESULTS: Lower mean daily temperatures were strongly
      associated with increased HF admissions and mortality with a cumulative (to
      23days) relative risk (RR) (95% confidence interval (CI)) for HF admissions of
      2.63 (2.43, 2.84) for an 11 degrees C. vs. a 25 degrees Cday, and cumulative
      (42days) RR (95% CI)=3.13 (1.90, 5.16) for HF mortality. The association with
      cold weather was stronger among older age groups and for new hospitalizations
      compared to recurrent ones, while presence of co-morbidities did not modify the
      association. Both high and low relative humidity were modestly associated with
      more admissions. CONCLUSIONS: Both HF admissions and mortality in Hong Kong were
      very strongly associated with cold temperatures. Reducing exposure to cold
      temperatures among those at risk for HF has the potential to reduce
      hospitalizations and mortality.

PMID- 27875732
TI  - Sirtuin 1 protects the aging heart from contractile dysfunction mediated through
      the inhibition of endoplasmic reticulum stress-mediated apoptosis in cardiac
      specific Sirtuin 1 knockout mouse model.
AB  - BACKGROUND: The longevity regulator Sirtuin 1 is an NAD+-dependent histone
      deacetylase that regulates endoplasmic reticulum stress and influences
      cardiomyocyte apoptosis during cardiac contractile dysfunction induced by aging.
      The mechanism underlying Sirtuin 1 function in cardiac contractile dysfunction
      related to aging has not been completely elucidated. METHODS: We evaluated
      cardiac contractile function, endoplasmic reticulum stress, apoptosis, and
      oxidative stress in 6- and 12month-old cardiac-specific Sirtuin 1 knockout (Sirt1
      /-) and control (Sirt1f/f) mice using western blotting and immunohistochemistry.
      Mice were injected with a protein disulphide isomerase inhibitor. For in vitro
      analysis, cultured H9c2 cardiomyocytes were exposed to either a Sirtuin 1
      inhibitor or activator, with or without a mitochondrial inhibitor, to evaluate
      the effects of Sirtuin 1 on endoplasmic reticulum stress, nitric oxide synthase
      expression, and apoptosis. The effects of protein disulphide isomerase inhibition
      on oxidative stress and ER stress-related apoptosis were also investigated.
      RESULTS: Compared with 6-month-old Sirt1f/f mice, marked impaired contractility
      was observed in 12-month-old Sirt1-/- mice. These findings were consistent with
      increased endoplasmic reticulum stress and apoptosis in the myocardium. Measures
      of oxidative stress and nitric oxide synthase expression were significantly
      higher in Sirt1-/- mice compared with those in Sirt1f/f mice at 6months. In vitro
      experiments revealed increased endoplasmic reticulum stress-mediated apoptosis in
      H9c2 cardiomyocytes treated with a Sirtuin 1 inhibitor; the effects were
      ameliorated by a Sirtuin 1 activator. Moreover, consistent with the in vitro
      findings, impaired cardiac contractility was demonstrated in Sirt1-/- mice
      injected with a protein disulphide isomerase inhibitor. CONCLUSION: The present
      study demonstrates that the aging heart is characterized by contractile
      dysfunction associated with increased oxidative stress and endoplasmic reticulum
      stress and Sirtuin 1 might have the ability to protect the aging hearts from the
      inhibition of endoplasmic reticulum-mediated apoptosis.

PMID- 27875734
TI  - Comparison of two commonly used clinical cognitive screening tests to diagnose
      mild cognitive impairment in heart failure with the golden standard European
      Consortium Criteria.
AB  - INTRODUCTION: This study on mild cognitive impairment (MCI) in heart failure (HF)
      compares the utility of Montreal Cognitive Assessment (MoCA) to the Mini-Mental
      Status Exam (MMSE) for diagnosing MCI in a HF population when compared to the
      golden standard European Consortium Criteria (ECC). METHODS: Participants were
      recruited from the Alberta HEART study at the Mazankowski Alberta Heart Institute
      in Edmonton and St. Mary's hospital in Camrose. This study enrolled 53 community
      adults aged>50years: 33 HF and 20 controls. Participants were assessed using both
      the MMSE and MoCA for MCI. MCI was diagnosed using the golden standard, European
      Consortium Criteria. Sensitivity and specificity analysis, positive and negative
      predictive values, likelihood ratios and kappa statistic were calculated.
      RESULTS: The mean age was 72.8years (SD 8.4), 60.4% were females and 34% had
      underlying ischemic heart disease. Overall, two thirds of patients (22/33, 66%)
      with HF had MCI. In comparison to European Consortium Criteria, the sensitivity
      and specificity of MoCA were 82% and 91% in identifying individuals with MCI, and
      MMSE were 9% and 91%, respectively. The positive and negative predictive values
      for MoCA were 95% and 71%, and for MMSE were 67% and 33%, respectively. Kappa
      statistics showed good agreement between MoCA and consortium criteria
      (kappa=0.68) and a low agreement between MMSE and consortium criteria
      (kappa=0.07). CONCLUSION: Cognitive dysfunction is common in patients with HF.
      Overall, the MoCA seems to be a better screening tool than MMSE for MCI in HF
      patients.

PMID- 27875733
TI  - Relationship between ambient temperature and frequency and severity of
      cardiovascular emergencies: A prospective observational study based on out-of
      hospital care data.
AB  - OBJECTIVE: To test the hypothesis that more cardiovascular emergencies occur at
      low rather than at high temperatures under moderate climatic conditions. METHODS:
      This was a prospective observational study performed in a prehospital setting.
      Data from the Emergency Medical Service in Hamburg (Germany) and from the local
      weather station were evaluated over a 5-year period. Temperature data were
      matched with the associated rescue mission data. Lowess-Regression analysis was
      performed to assess the relationship between the temperature and the frequency of
      individual cardiovascular emergencies. In addition, three threshold-temperatures
      (0 degrees C, 10 degrees C, 20 degrees C) were defined in order to determine the
      frequency of cardiovascular emergencies above and below each cut-off value. The
      severity of emergencies was assessed using the National Advisory Committee for
      Aeronautics (NACA) scoring system. RESULTS: A total of 35,390 cardiovascular
      emergencies were treated by Emergency Physicians. Transient Loss of Consciousness
      increased at high temperatures (above 20 degrees C): +43% (95%-CI: [27%; 59%]).
      In contrast, Coronary Artery Disease +26% (95%-CI: [17%; 34%]), Cardiac Pulmonary
      Edema +21% (95%-CI: [14%; 27%]), Hypertensive Urgency +18% (95%-CI: [10%; 25%])
      and Cerebrovascular Accident +17% (95%-CI: [8%; 24%]) increased at low
      temperatures, particularly below 10 degrees C (significance level for all:
      p<0.001). No temperature-related effect was seen in Cardiac Arrhythmia and
      Pulmonary Embolism and no significant correlation was found between the severity
      of emergencies and temperature. CONCLUSIONS: Our findings suggest that some
      cardiovascular emergencies such as Coronary Artery Disease, Cardiac Pulmonary
      Edema, Hypertensive Urgency and Cerebrovascular Accident are more frequent in low
      temperatures even under mild climatic conditions.

PMID- 27875735
TI  - Superior long term outcome associated with native vessel versus graft vessel PCI
      following secondary PCI in patients with prior CABG.
AB  - BACKGROUND: Secondary percutaneous coronary intervention (PCI) in patients with
      prior coronary artery bypass graft surgery is increasingly common. Graft vessel
      PCI has higher rates of adverse events compared with native coronary vessel PCI.
      AIM: To investigate the clinical outcomes of patients with prior CABG who
      underwent secondary PCI of either a graft vessel (GV), a native coronary vessel
      (NV) or both graft and native (NG) vessels. METHODS: 220 patients (84% male) who
      underwent PCI in our institution to either GV (n=89), NV (n=103) or both GV and
      NV (NG group) (n=28) were studied. The study population underwent 378 procedures
      (GV group; n=126, NV group; n=164 and NG group; n=88). Median follow up was for
      36months [range 2-75months]. RESULTS: Target vessel revascularisation (TVR)
      occurred in 12.5% of the GV group and 3.6% in the NV group [p=0.0004], and was
      predominantly due to in-stent restenosis. Patients who had PCI due to TVR were
      more likely to suffer from diabetes and peripheral vascular disease. History of
      chronic renal failure was associated with higher risk (HR 2.21, p=0.005) whereas
      preserved left ventricular ejection fraction (LVEF) with lower risk (HR 0.17,
      p=0.0007) of death. The median survival (interval between CABG and end of follow
      up period) was lower in the GV compared with the NV group (315 vs 372months
      p=0.005). CONCLUSION: This registry demonstrates inferior long term outcome for
      patients undergoing secondary PCI of GV versus NV. Where possible, a strategy of
      NV rather than GV target PCI should be considered in patients with prior CABG.
      CONDENSED ABSTRACT: Secondary PCI in patients with prior CABG surgery is
      increasingly common. Graft vessel PCI has inferior outcomes with high rates of
      restenosis and occlusion compared with native coronary vessel PCI. We studied the
      clinical outcomes of 220 patients with prior CABG who underwent secondary PCI to
      either a graft vessel (GV), a native coronary vessel (NV) or both graft and
      native (NG) vessels. Target vessel revascularisation was 5 times higher in the GV
      compared with the NV group. History of CRF and impaired left ventricular function
      were associated with higher risk of death. We also found that the median survival
      (interval between CABG and end of follow-up period) was better in the NV group
      compared with GV group. This registry study demonstrates inferior long term
      outcome for patients undergoing secondary PCI of GV. A strategy of NV rather than
      GV target PCI should be considered in patients with prior CABG.

PMID- 27875736
TI  - Emerging roles and mechanisms of long noncoding RNAs in atherosclerosis.
AB  - Atherosclerosis is the most common cause of heart attacks, strokes, and
      peripheral vascular disease. Atherosclerosis is predicted to be the primary cause
      of death in the world by 2020. Increasing evidence suggests that long non-protein
      coding RNAs (lncRNAs) are important for the regulation of tissue homeostasis and
      pathophysiological conditions. Although knowledge about lncRNAs in
      atherosclerosis and other cardiovascular diseases is sparse, lncRNAs are
      clinically interesting because of their diagnostic and therapeutic value. This
      review summarizes knowledge about lncRNAs through their actions, related research
      methods and effects on atherosclerosis to provide helpful insights about how
      lncRNAs work and control atherosclerosis process and how lncRNA-related
      strategies could benefit human beings.

PMID- 27875737
TI  - Experimental evidence for a severe proarrhythmic potential of levosimendan.
AB  - BACKGROUND: The calcium sensitizer levosimendan is established for therapy of
      acutely decompensated congestive heart failure. Clinical experience suggests a
      possible proarrhythmic potential. The aim of the present study was to assess
      possible proarrhythmic effects and underlying electrophysiological mechanisms.
      METHODS AND RESULTS: Ten rabbit hearts were isolated and Langendorff-perfused.
      Thereafter, levosimendan was infused in 3 concentrations (0.5, 1, and 2MUM).
      Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed
      a dose-dependent reduction of QT interval (0.5MUM: -27ms, 1MUM:-33ms, 2MUM: 
      77ms; p<0.05) and action potential duration at 90% of repolarization (APD90;
      0.5MUM: -12ms, 1MUM: -12ms, 2MUM: -20ms). There was no significant increase in
      dispersion of repolarization. The described abbreviation of myocardial
      repolarization was accompanied by a significant decrease of effective refractory
      period (ERP; 0.5MUM: -16ms, 1MUM: -20ms, 2MUM:-27ms; p<0.05). Under baseline
      conditions, ventricular fibrillation was inducible by programmed stimulation and
      aggressive burst stimulation in 3 of 10 hearts (4 episodes). After application of
      1MUM levosimendan, 8 of 10 control hearts were inducible (27 episodes). Of note,
      in 8 of 10 hearts after infusion of up to 2MUM levosimendan, incessant
      ventricular fibrillation that could not be terminated by multiple external
      defibrillations occurred. CONCLUSION: In the present study, acute infusion of
      levosimendan resulted in an abbreviation of ventricular repolarization and a
      reduction of ERP. This led to a significantly elevated inducibility of
      ventricular fibrillation. In 8 of 10 hearts, incessant ventricular fibrillation
      occurred. These results suggest a proarrhythmic effect of levosimendan and might
      explain an increased mortality that coincided levosimendan treatment in a few
      small clinical studies.

PMID- 27875738
TI  - Heart rate response to exercise in heart failure patients: The prognostic role of
      metabolic-chronotropic relation and heart rate recovery.
AB  - BACKGROUND: The dynamics of the sinus node response to exercise is linked to
      functional capacity and outcome in heart failure (HF). The goal of the work was
      to analyze determinants and impacts of cardio-acceleration, described by the
      concept of metabolic-chronotropic relation (MCR) and of cardio-deceleration,
      described by heart rate recovery (HRR). METHODS: A cohort of 25 healthy controls
      and 78 patients with advanced systolic HF and optimized medical and/or device
      therapy (97% receiving beta-blockers, 54% ICD) underwent maximal cardiopulmonary
      exercise test and were prospectively followed. RESULTS: HF patients had impaired
      exercise performance compared with controls (pVO2 15+/-4 vs. 29+/-7ml.kg-1.min-1,
      p<0.0001) and lower both MCR slope (0.54+/-0.24 vs. 0.90+/-0.15, p<0.0001) and
      HRR (14.7+/-7.9 vs. 18.3+/-4.2min-1, p=0.03). In HF patients, MCR slope was
      inversely associated with beta-blocker dose (r=-0.24), NYHA class (r=-0.28) and
      HF duration (r=-0.25), whereas HRR with estimated glomerular filtration rate
      (eGFR, r=0.39), age (r=-0.28) and BMI (r=-0.31, all p<0.05). During a follow-up
      of 1269+/-933days, 64% patients experienced an adverse outcome (death, urgent
      transplantation, left ventricular assist device implantation). Those patients had
      higher NT-proBNP (p=0.02), worse left ventricular systolic function (LVEF,
      p=0.03) and lower MCR slope (p=0.02) but not HRR (p=0.19). MCR slope (but not
      HRR) was a significant outcome predictor (p=0.02 for Cox unadjusted model) even
      after adjustment for LVEF, serum natrium, systolic blood pressure, eGFR and NT
      proBNP (p=0.04). CONCLUSION: MCR slope is associated with different clinical
      variables than HRR. Compared to HRR, MCR slope provides significant prognostic
      information in HF patients.

PMID- 27875739
TI  - Plasma levels of atrial and brain natriuretic peptides in apparently healthy
      subjects: Effects of sex, age, and hemoglobin concentration.
AB  - BACKGROUND: To examine whether the use of one value of natriuretic peptides to
      define "normal" is appropriate in all individuals, and to assess the influence of
      sex, age, and other variables on atrial and brain natriuretic peptides (ANP, BNP)
      levels. METHODS AND RESULTS: A total of 1375 apparently healthy people
      (women:155, men:1220), aged 18-70years were enrolled. Both ANP and BNP levels
      were higher in women than in men (ANP: 12.50+/-6.82pg/mL vs 8.18+/-4.19pg/mL;
      BNP: 9.85+/-7.63pg/mL vs 7.03+/-6.97pg/mL). The subjects were divided into three
      age groups: group I, 18-30years; group II, 30-50years; group III, 50-70years.
      First, the influence of age on ANP and BNP levels was examined. In women, both
      ANP and BNP levels were higher in groups II and III than those in group I. In
      men, ANP and BNP levels increased with age. Second, sex differences in ANP and
      BNP levels due to age were examined. ANP level was higher in women than that in
      men in all age groups. BNP level was higher in women than that in men in groups I
      and II. Multivariate analysis indicated that both ANP and BNP levels were
      influenced by age, hemoglobin level, and platelet counts. CONCLUSION: Because ANP
      and BNP levels in healthy subjects are influenced by sex, age, and hemoglobin
      levels, the use of a single value to define "normal" in all individuals is not
      appropriate.

PMID- 27875740
TI  - Conditional knockout of TFPI-1 in VSMCs of mice accelerates atherosclerosis by
      enhancing AMOT/YAP pathway.
AB  - BACKGROUND: Tissue factor pathway inhibitor-1 (TFPI-1) has multiple functions and
      its precise role and molecular mechanism during the development of
      atherosclerosis are not clear. OBJECTIVES: To determine the effect and molecular
      mechanism of TFPI-1 deficiency in vascular smooth muscle cells (VSMCs) in
      atherosclerosis in the apolipoprotein E knockout (ApoE-/-) mouse. METHODS AND
      RESULTS: A mouse model with a conditional knockout of TFPI-1 in VSMCs in an
      atherosclerosis-prone background (ApoE-/-) was generated. Mice were fed a high
      fat diet for 18weeks and were then euthanized. Arterial trees and aortas were
      stained with Sudan IV and were labeled via immunohistochemistry. Cell
      proliferation and migration of VSMCs in atherosclerotic plaques were assessed.
      More atherosclerotic lesions and higher levels of proliferation and migration of
      VSMCs were observed in TFPI-1fl/fl/Sma-Cre+ApoE-/-mice. An interaction between
      TFPI-1 and angiomotin (AMOT) was identified in human VSMCs by mass spectrometry,
      immunoprecipitation and co-localization analyses. Signal pathway changes were
      detected by Western blot analysis, and the expression levels of target genes were
      determined by real-time PCR. Decreased phosphorylation of AMOT and Yes-associated
      protein 1 (YAP) in TFPI-1fl/fl/Sma-Cre+ApoE-/- mice resulted in increased
      expression levels of snail family zinc finger 2 (SLUG) and connective tissue
      growth factor (CTGF), which are target genes of the Hippo signaling pathway that
      have been verified as atherosclerosis candidate genes. CONCLUSION: Deficiency in
      TFPI-1 in the VSMCs of ApoE-/- mice accelerated the development of
      atherosclerosis by promoting the proliferation and migration of VSMCs which may
      be caused by the decreased phosphorylation of AMOT and YAP. SIGNIFICANCE: TFPI-1
      has been found to has an anticoagulant activity, induce cell apoptosis and
      prevent cell proliferation. For the first time, we constructed a line of
      conditional knockout mice in which the TPFI-1 gene is deleted in VSMCs. We found
      that TFPI-1 deficiency clearly promoted the development of atherosclerosis when
      these mice were crossed into an ApoE-/-background. One notable feature of
      atherosclerosis is the proliferation and migration of smooth muscle cells.
      Previous reports involved TFPI-1 do not completely explain the proliferation and
      migration of VSMCs because heterozygous TF deficient (TF+/-) mice bred in an ApoE
      /- background did not show diminished atherosclerosis compared to TF+/+ mice bred
      in the same background. Our results first confirmed that TFPI-1 interacts with
      AMOT, which led to a decrease in the phosphorylation of YAP and further increased
      the genes expression of the proliferation and migration involved. Our results
      further confirmed that atherosclerosis was a localized disease.

PMID- 27875741
TI  - A contrast enhancement method for improving the segmentation of breast lesions on
      ultrasonography.
AB  - PURPOSE: This paper presents an adaptive contrast enhancement method based on
      sigmoidal mapping function (SACE) used for improving the computerized
      segmentation of breast lesions on ultrasound. METHODS: First, from the original
      ultrasound image an intensity variation map is obtained, which is used to
      generate local sigmoidal mapping functions related to distinct contextual
      regions. Then, a bilinear interpolation scheme is used to transform every
      original pixel to a new gray level value. Also, four contrast enhancement
      techniques widely used in breast ultrasound enhancement are implemented:
      histogram equalization (HEQ), contrast limited adaptive histogram equalization
      (CLAHE), fuzzy enhancement (FEN), and sigmoid based enhancement (SEN). In
      addition, these contrast enhancement techniques are considered in a computerized
      lesion segmentation scheme based on watershed transformation. The performance
      comparison among techniques is assessed in terms of both the quality of contrast
      enhancement and the segmentation accuracy. The former is quantified by the
      measure, where the greater the value, the better the contrast enhancement,
      whereas the latter is calculated by the Jaccard index, which should tend towards
      unity to indicate adequate segmentation. RESULTS: The experiments consider a data
      set with 500 breast ultrasound images. The results show that SACE outperforms its
      counterparts, where the median values for the measure are: SACE: 139.4, SEN:
      68.2, HEQ: 64.1, CLAHE: 62.8, and FEN: 7.9. Considering the segmentation
      performance results, the SACE method presents the largest accuracy, where the
      median values for the Jaccard index are: SACE: 0.81, FEN: 0.80, CLAHE: 0.79, HEQ:
      77, and SEN: 0.63. CONCLUSION: The SACE method performs well due to the
      combination of three elements: (1) the intensity variation map reduces intensity
      variations that could distort the real response of the mapping function, (2) the
      sigmoidal mapping function enhances the gray level range where the transition
      between lesion and background is found, and (3) the adaptive enhancing scheme for
      coping with local contrasts. Hence, the SACE approach is appropriate for
      enhancing contrast before computerized lesion segmentation.

PMID- 27875742
TI  - Map-based cloning and characterization of the novel yellow-green leaf gene ys83
      in rice (Oryza sativa).
AB  - Leaf-color mutants have been extensively studied in rice, and many corresponding
      genes have been identified up to now. However, leaf-color mutation mechanisms are
      diverse and still need further research through identification of novel genes. In
      the present paper, we isolated a leaf-color mutant, ys83, in rice (Oryza sativa).
      The mutant displayed a yellow-green leaf phenotype at seedling stage, and then
      slowly turned into light-green leaf from late tillering stage. In its yellow
      leaves, photosynthetic pigment contents significantly decreased and the
      chloroplast development was retarded. The mutant phenotype was controlled by a
      recessive mutation in a nuclear gene on the short arm of rice chromosome 2. Map
      based cloning and sequencing analysis suggested that the candidate gene was YS83
      (LOC_Os02g05890) encoding a protein containing 165 amino acid residues. Gene YS83
      was expressed in a wide range of tissues, and its encoded protein was targeted to
      the chloroplast. In the mutant, a T-to-A substitution occurred in coding sequence
      of gene YS83, which caused a premature translation of its encoded product. By
      introduction of the wild-type gene, the ys83 mutant recovered to normal green
      leaf phenotype. Taken together, we successfully identified a novel yellow-green
      leaf gene YS83. In addition, number of productive panicles per plant and number
      of spikelets per panicle only reduced by 6.7% and 7.6%, respectively, meanwhile
      its seed setting rate and 1000-grain weight (seed size) were not significantly
      affected in the mutant, so leaf-color mutant gene ys83 could be used as a trait
      marker gene in commercial hybrid rice production.

PMID- 27875743
TI  - From the struggle of defining to the understanding of dignity: A commentary on
      Barclay (2016) "In sickness and in dignity: A philosophical account of the
      meaning of dignity in health care".

PMID- 27875744
TI  - Identification of protein secondary structures by laser induced autofluorescence:
      A study of urea and GnHCl induced protein denaturation.
AB  - In the present study an attempt has been made to interrogate the bulk secondary
      structures of some selected proteins (BSA, HSA, lysozyme, trypsin and
      ribonuclease A) under urea and GnHCl denaturation using laser induced
      autofluorescence. The proteins were treated with different concentrations of urea
      (3M, 6M, 9M) and GnHCl (2M, 4M, 6M) and the corresponding steady state
      autofluorescence spectra were recorded at 281nm pulsed laser excitations. The
      recorded fluorescence spectra of proteins were then interpreted based on the
      existing PDB structures of the proteins and the Trp solvent accessibility
      (calculated using "Scratch protein predictor" at 30% threshold). Further, the
      influence of rigidity and conformation of the indole ring (caused by protein
      secondary structures) on the intrinsic fluorescence properties of proteins were
      also evaluated using fluorescence of ANS-HSA complexes, CD spectroscopy as well
      as with trypsin digestion experiments. The outcomes obtained clearly demonstrated
      GnHCl preferably disrupt helix as compared to the beta beta-sheets whereas, urea
      found was more effective in disrupting beta-sheets as compared to the helices.
      The other way round the proteins which have shown detectable change in the
      intrinsic fluorescence at lower concentrations of GnHCl were rich in helices
      whereas, the proteins which showed detectable change in the intrinsic
      fluorescence at lower concentrations of urea were rich in beta-sheets. Since high
      salt concentrations like GnHCl and urea interfere in the secondary structure
      analysis by circular dichroism Spectrometry, the present method of analyzing
      secondary structures using laser induced autofluorescence will be highly
      advantageous over existing tools for the same.

PMID- 27875745
TI  - Water as probe molecule for midgap states in nanocrystalline strontium titanate
      by conventional and synchronous luminescence spectroscopy under ambient
      conditions.
AB  - Alkaline earth metal titanates are broad bandgap semiconductors with applications
      in electronic devices, as catalysts, photocatalysts, sorbents, and sensors.
      Strontium titanate SrTiO3 is of interest in electronic devices, sensors, in the
      photocatalytic hydrogen generation, as catalyst and sorbent. Both photocatalysis
      and operation of electronic devices rely upon the pathways of relaxation of
      excited charge in the semiconductor, including relaxation through the midgap
      states. We report characterization of nanocrystalline SrTiO3 at room temperature
      by "conventional" vs. synchronous luminescence spectroscopy and complementary
      methods. We determined energies of radiative transitions in the visible range
      through the two midgap states in the nanocrystalline SrTiO3. Further, adsorption
      and desorption of vapor of water as "probe molecule" for midgap states in the
      nanocrystalline SrTiO3 was studied, for the first time, by luminescence
      spectroscopy under ambient conditions. Emission of visible light from the
      nanocrystalline SrTiO3 is significantly increased upon desorption of water and
      decreased (quenched) upon adsorption of water vapor, due to interactions with the
      surface midgap states.

PMID- 27875746
TI  - De novo and inherited SCN8A epilepsy mutations detected by gene panel analysis.
AB  - OBJECTIVES: To determine the incidence of pathogenic SCN8A variants in a cohort
      of epilepsy patients referred for clinical genetic testing. We also investigated
      the contribution of SCN8A to autism spectrum disorder, intellectual disability,
      and neuromuscular disorders in individuals referred for clinical genetic testing
      at the same testing laboratory. METHODS: Sequence data from 275 epilepsy panels
      screened by Emory Genetics Laboratory were reviewed for variants in SCN8A. Two
      additional cases with variants in SCN8A were ascertained from other testing
      laboratories. Parental samples were tested for variant segregation and clinical
      histories were examined. SCN8A variants detected from gene panel analyses for
      autism spectrum disorder, intellectual disability, and neuromuscular disorders
      were also examined. RESULTS: Five variants in SCN8A were identified in five
      individuals with epilepsy. Three variants were de novo, one was inherited from an
      affected parent, and one was inherited from an unaffected parent. Four of the
      individuals have epilepsy and developmental delay/intellectual disability. The
      remaining individual has a milder epilepsy presentation without cognitive
      impairment. We also identified an amino acid substitution at an evolutionarily
      conserved SCN8A residue in a patient who was screened on the autism spectrum
      disorder panel. Additionally, we examined the distribution of pathogenic SCN8A
      variants across the Nav1.6 channel and identified four distinct clusters of
      variants. These clusters are primarily located in regions of the channel that are
      important for the kinetics of channel inactivation. CONCLUSIONS: Variants in
      SCN8A may be responsible for a spectrum of epilepsies as well as other
      neurodevelopmental disorders without seizures. The predominant pathogenic
      mechanism appears to involve disruption of channel inactivation, leading to gain
      of-function effects.

PMID- 27875747
TI  - New model of pharmacoresistant seizures induced by 3-mercaptopropionic acid in
      mice.
AB  - About 30% of the patients with epilepsy do not respond to clinically established
      anticonvulsants, despite having effective concentrations of the antiepileptic
      drug in plasma. Therefore, new preclinical models of epilepsy are needed to
      identify more efficacious treatments. We describe here a new drug-resistant
      seizure model in mice to be used at the early stages of pre-clinical trials. This
      model consists in inducing daily generalized seizures for 23 consecutive days by
      administration of 3-mercaptopropionic acid (MP). As a result, 100% of animals
      become resistant to phenytoin and 80% to phenobarbital. Such resistance is
      strongly associated with the overexpression of P-glycoprotein (Pgp), observed in
      cerebral cortex, hippocampus and striatum while resistance to Pgp nonsubstrate
      drugs such as carbamazepine, diazepam and levetiracetam is not observed. This
      model could be useful for screening novel anticonvulsant drugs with a potential
      effect on pharmacoresistant seizures treatment.

PMID- 27875748
TI  - Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in
      BV2 microglia.
AB  - Piperine, the chief alkaloid isolated from Piper nigrum, has been known to have
      anti-inflammatory effect. However, the effects of piperine on neuroinflammation
      have not been reported. In the present study, we evaluated the effects of
      piperine on neuroinflammation in BV2 microglia and investigated the molecular
      mechanism. The results showed that piperine significantly inhibited LPS-induced
      TNF-alpha, IL-6, IL-1beta, and PGE2 production in BV2 cells. Western blot
      analysis showed that piperine dose-dependently inhibited LPS-induced NF-kappaB
      activation. Furthermore, piperine was found to amplify the expression of Nrf2 and
      HO-1 up-regulated by LPS. In addition, the inhibition of inflammatory mediators
      by piperine can be reversed by transfection with Nrf2 siRNA. In conclusion,
      piperine inhibited LPS-induced inflammatory response by activating Nrf2 signaling
      pathway. These results indicated that piperine may be a promising agent for the
      treatment of neurodegenerative diseases.

PMID- 27875750
TI  - How children's victimization relates to distorted versus sensitive social
      cognition: Perception, mood, and need fulfillment in response to Cyberball
      inclusion and exclusion.
AB  - This study examined whether victimization is associated with negatively distorted
      social cognition (bias), or with a specific increased sensitivity to social
      negative cues, by assessing the perception of social exclusion and the
      consequences for psychological well-being (moods and fundamental needs). Both
      self-reported and peer-reported victimization of 564 participants (Mage=9.9years,
      SD=1.04; 49.1% girls) were measured, and social exclusion was manipulated through
      inclusion versus exclusion in a virtual ball-tossing game (Cyberball). Children's
      perceptions and psychological well-being were in general more negative after
      exclusion than after inclusion. Moreover, self-reported-but not peer-reported
      victimization was associated with the perception of being excluded more and
      receiving the ball less, as well as more negative moods and less fulfillment of
      fundamental needs, regardless of being excluded or included during the Cyberball
      game. In contrast, peer-reported victimization was associated with more negative
      mood and lower need fulfillment in the exclusion condition only. Together, these
      results suggest that children who themselves indicate being victimized have
      negatively distorted social cognition, whereas children who are being victimized
      according to their peers experience increased sensitivity to negative social
      situations. The results stress the importance of distinguishing between self
      reported and peer-reported victimization and have implications for interventions
      aimed at victimized children's social cognition.

PMID- 27875749
TI  - Systematic investigation on the turning point of over-inflammation to
      immunosuppression in CLP mice model and their characteristics.
AB  - Immunosuppression is involved in refractory innate and adaptive immune responses
      and is considered to be the predominant driving force for mortality in sepsis.
      The cecal ligation and puncture (CLP) model is regarded as a golden standard
      model for sepsis study, but the turning point of over-inflammation to
      immunosuppression was reported differently. Herein, systematic investigation on
      the turning point of over-inflammation to immunosuppression in CLP mice model was
      carried out. The results showed only the mortality of mice challenged with of
      Pseudomonas aeruginosa on Day 1 not other days after the surgery was higher than
      that of other mice with Sham surgery, suggesting Day 1 after the CLP surgery
      might be the turning point. There was very low mortality even without death in
      Sham mice but the mortality was 80% after mice were challenged with 2.5*107,
      5.0*106 and 1.0*106CFU/10g of Pseudomonas aeruginosa, further demonstrating Day 1
      after the CLP surgery was the turning point. And, CLP mice presented low levels
      of pro-inflammatory and anti-inflammatory cytokines, and high bacterial loads on
      Day 1. Additionally, the amounts and proportion of blood cells and monocytes
      significantly changed, too. In conclusion, Day 1 after the CLP surgery was the
      turning point of over-inflammation to immunosuppression, and low levels of
      cytokines and high bacterial loads were the characteristics of this model on Day
      1, which is significant for pharmacological investigation on sepsis.

PMID- 27875751
TI  - All-in-one dual-aptasensor capable of rapidly quantifying carcinoembryonic
      antigen.
AB  - Using a dual DNA aptamer (CEA aptamer linked to hemin aptamer), capable of
      rapidly capturing carcinoembryonic antigen (CEA) and hemin, an all-in-one dual
      aptasensor with 1,1'-oxalyldiimidazole (ODI) chemiluminescence detection was
      developed for the early diagnosis of human cancer. CEA and hemin competitively
      bound with the dual DNA aptamer while the mixture in a detection cell was
      incubated for 30min at room temperature. When Amplex Red and H2O2 were added in
      the detection cell after the incubation, the yield of resorufin formed from the
      reaction Amplex Red and H2O2 depended on the concentration of HRP-mimicking G
      quardruplex DNAzyme formed from the binding interaction between hemin and the
      dual DNA aptamer. Bright red light was observed with the addition of ODI and H2O2
      in the detection cell containing resorufin. Relative CL intensity of all-in-one
      dual-aptasensor, operated with the competitive reaction of CEA and hemin in the
      presence of the dual aptamer, was exponentially decreased with the increase of
      CEA concentration in human serum. The limit of detection (LOD=3sigma) of the all
      in-one dual-aptasensor which operated with excellent accuracy, precision, and
      reproducibility was as low as 0.58ng/ml. The good correlation between the easy to
      use all-in-one dual-aptasensor and conventional enzyme-linked immunosorbent assay
      (ELISA), operated with time consuming procedures (e.g., long incubations and
      multiple washings), indicates that the rapid all-in-one dual-aptasensor can be
      applied as a novel clinical tool for the early diagnosis of breast cancer.

PMID- 27875752
TI  - Toxicity evaluation of e-juice and its soluble aerosols generated by electronic
      cigarettes using recombinant bioluminescent bacteria responsive to specific
      cellular damages.
AB  - Electronic-cigarettes (e-cigarette) are widely used as an alternative to
      traditional cigarettes but their safety is not well established. Herein, we
      demonstrate and validate an analytical method to discriminate the deleterious
      effects of e-cigarette refills (e-juice) and soluble e-juice aerosol (SEA) by
      employing stress-specific bioluminescent recombinant bacterial cells (RBCs) as
      whole-cell biosensors. These RBCs carry luxCDABE-operon tightly controlled by
      promoters that specifically induced to DNA damage (recA), superoxide radicals
      (sodA), heavy metals (copA) and membrane damage (oprF). The responses of the RBCs
      following exposure to various concentrations of e-juice/SEA was recorded in real
      time that showed dose-dependent stress specific-responses against both the e
      juice and vaporized e-juice aerosols produced by the e-cigarette. We also
      established that high doses of e-juice (4-folds diluted) lead to cell death by
      repressing the cellular machinery responsible for repairing DNA-damage,
      superoxide toxicity, ion homeostasis and membrane damage. SEA also caused the
      cellular damages but the cells showed enhanced bioluminescence expression without
      significant growth inhibition, indicating that the cells activated their global
      defense system to repair these damages. DNA fragmentation assay also revealed the
      disintegration of total cellular DNA at sub-toxic doses of e-juice. Despite their
      state of matter, the e-juice and its aerosols induce cytotoxicity and alter
      normal cellular functions, respectively that raises concerns on use of e
      cigarettes as alternative to traditional cigarette. The ability of RBCs in
      detecting both harmful effects and toxicity mechanisms provided a fundamental
      understanding of biological response to e-juice and aerosols.

PMID- 27875753
TI  - Searching for anomalous methane in shallow groundwater near shale gas wells.
AB  - Since the 1800s, natural gas has been extracted from wells drilled into
      conventional reservoirs. Today, gas is also extracted from shale using high
      volume hydraulic fracturing (HVHF). These wells sometimes leak methane and must
      be re-sealed with cement. Some researchers argue that methane concentrations, C,
      increase in groundwater near shale-gas wells and that "fracked" wells leak more
      than conventional wells. We developed techniques to mine datasets of groundwater
      chemistry in Pennsylvania townships where contamination had been reported. Values
      of C measured in shallow private water wells were discovered to increase with
      proximity to faults and to conventional, but not shale-gas, wells in the entire
      area. However, in small subareas, C increased with proximity to some shale-gas
      wells. Data mining was used to map a few hotspots where C significantly
      correlates with distance to faults and gas wells. Near the hotspots, 3 out of 132
      shale-gas wells (~2%) and 4 out of 15 conventional wells (27%) intersect faults
      at depths where they are reported to be uncased or uncemented. These results
      demonstrate that even though these data techniques do not establish causation,
      they can elucidate the controls on natural methane emission along faults and may
      have implications for gas well construction.

PMID- 27875754
TI  - The impact of diet and arginine supplementation on pancreatic mass, digestive
      enzyme activity, and insulin-containing cell cluster morphology during the
      estrous cycle in sheep.
AB  - To determine the effect of feed intake and arginine treatment during different
      stages of the estrous cycle on pancreatic mass, digestive enzyme activity, and
      histological measurements, ewes (n = 120) were randomly allocated to 1 of 3
      dietary groups; control (CON; 2.14-Mcal metabolizable energy/kg), underfed (UF;
      0.6 * CON), or overfed (OF; 2 * CON) over 2 yr. Estrus was synchronized using a
      controlled internal drug release device for 14 d. At controlled internal drug
      release withdrawal, ewes from each dietary group were assigned to 1 of 2
      treatments; Arg (L-Arg HCl, 155-MUmol/kg BW) or Sal (approximately 10-mL saline).
      Treatments were administered 3 times daily via jugular catheter and continued
      until slaughter on d (day) 5 and 10 of the second estrus cycle (early luteal
      phase, n = 41 and mid-luteal phase, n = 39; yr 1) and d 15 of the first estrus
      cycle (late luteal phase, n = 40; yr 2). A blood sample collected from jugular
      catheters for serum insulin analysis before slaughter. The pancreas was then
      removed, trimmed of mesentery and fat, weighed, and a sample snap-frozen until
      enzyme analysis. Additional pancreatic samples were fixed in 10% formalin
      solution for histological examination of size and distribution of insulin
      containing cell clusters. Data were analyzed as a completely randomized design
      with a factorial arrangement of treatments. Diet, treatment, and diet * treatment
      were blocked by yr and included in the model with initial BW used as a covariate.
      Day of the estrous cycle was initially included in the model but later removed as
      no effects (P > 0.10) were observed for any pancreatic variables tested. Overfed
      ewes had the greatest (P < 0.001) change in BW, final BW, change in BCS, and
      final BCS. A diet * treatment interaction was observed for change in BW and final
      BW (P <= 0.004). Overfed and CON had increased (P < 0.001) pancreas weight (g)
      compared with UF ewes. Protein concentration (g/pancreas) was the lowest (P <
      0.001) in UF ewes, whereas protein content (mg/kg BW) was greater (P = 0.03) in
      UF than OF ewes. Activity of alpha-amylase (U/g, kU/pancreas, U/kg of BW, and U/g
      protein) and trypsin (U/pancreas) was greater (P <= 0.003) in OF than UF ewes.
      Serum insulin was the greatest (P < 0.001) in OF ewes. No effects were observed
      for pancreatic insulin-containing cell clusters. This study demonstrated that
      plane of nutrition affected several measurements of pancreatic function; however,
      the dosage of Arg used did not influence pancreatic function.

PMID- 27875755
TI  - Individual differences in brainstem and basal ganglia structure predict postural
      control and balance loss in young and older adults.
AB  - It remains unclear which specific brain regions are the most critical for human
      postural control and balance, and whether they mediate the effect of age. Here,
      associations between postural performance and corticosubcortical brain regions
      were examined in young and older adults using multiple structural imaging and
      linear mixed models. Results showed that of the regions involved in posture, the
      brainstem was the strongest predictor of postural control and balance: lower
      brainstem volume predicted larger center of pressure deviation and higher odds of
      balance loss. Analyses of white and gray matter in the brainstem showed that the
      pedunculopontine nucleus area appeared to be critical for postural control in
      both young and older adults. In addition, the brainstem mediated the effect of
      age on postural control, underscoring the brainstem's fundamental role in aging.
      Conversely, lower basal ganglia volume predicted better postural performance,
      suggesting an association between greater neural resources in the basal ganglia
      and greater movement vigor, resulting in exaggerated postural adjustments.
      Finally, results showed that practice, shorter height and heavier weight (i.e.,
      higher body mass index), higher total physical activity, and larger ankle active
      (but not passive) range of motion were predictive of more stable posture,
      irrespective of age.

PMID- 27875757
TI  - The effect of body mass index on fluoroscopy time and radiation dose in intra
      articular glenohumeral joint injections.
AB  - PURPOSE: To determine the relationship between body mass index (BMI) and
      fluoroscopy time and radiation dose during fluoroscopy-guided glenohumeral joint
      injections. METHODS: This was a retrospective analysis of prospectively collected
      data. Physicians with board certification in Physical Medicine and Rehabilitation
      and/or Sports Medicine performed or supervised all injections. BMI was calculated
      within three months of the injection. Fluoroscopy time and radiation dose data
      were recorded by the fluoroscopy system and transcribed into the clinical
      database after each procedure. RESULTS: A total of 335 intra-articular GHJ
      injections were performed, 230 on the right shoulder and 105 on the left
      shoulder; none were bilateral. The mean fluoroscopy time for all injections was
      18.8+/-12.6s, and the mean radiation DAP was 656+/-1190mGy-cm2. There was no
      significant difference in fluoroscopy time or dose between first-time and repeat
      injections (P=.405; P=.011) and no significant differences in fluoroscopy time or
      radiation dose when a trainee was involved (P=.756 for time and P=.149 for dose).
      Needle lengths of 1.5, 2.5, or 3.5in. were used during the injection, and there
      was no significant difference in needle length selection between BMI groups
      (P=.319). CONCLUSIONS: Intra-articular glenohumeral joint injection fluoroscopy
      time and radiation dose are not affected by body mass index, age, gender, trainee
      involvement, first versus repeat injection, or needle length. This procedure is
      associated with a dose of radiation that likely has minimal to no clinical
      significance.

PMID- 27875756
TI  - Patterns of cortisol and alpha-amylase reactivity to psychosocial stress in
      maltreated women.
AB  - BACKGROUND: Childhood maltreatment can trigger enduring changes in major stress
      response systems, particularly in the context of major depressive disorder (MDD).
      However, the relative impact of maltreatment versus MDD on hypothalamic-pituitary
      adrenal axis and sympathetic-adrenal-medullary system stress reactivity is not
      well understood. METHOD: This study examined salivary cortisol and alpha-amylase
      responses to the Trier Social Stress Test (TSST) in 26 maltreated (15 with
      current MDD) and 26 non-maltreated (17 with current MDD) women. RESULTS:
      Maltreated women showed greater anticipatory cortisol reactivity during the TSST
      protocol compared to non-maltreated women. Maltreated women also showed rapid
      deceleration in cortisol levels. Whereas non-maltreated women showed initial
      declines in alpha-amylase levels but rapidly increasing alpha-amylase levels
      during the TSST protocol, maltreated women did not exhibit changes in alpha
      amylase levels during the TSST protocol. Contrary to expectation, MDD did not
      impact cortisol or alpha-amylase responses. LIMITATIONS: The present study is
      limited by retrospective report of childhood maltreatment, cross-sectional
      design, and modest sample sizes. CONCLUSIONS: These findings suggest that
      childhood maltreatment plays a greater role driving alterations in cortisol and
      alpha-amylase stress reactivity than MDD. Understanding the biological embedding
      of maltreatment is critical for elucidating mechanisms linking these experiences
      to risk for negative mental and physical health outcomes.

PMID- 27875759
TI  - Round ligament leiomyoma: a rare manifestation of a common entity.
AB  - A 68-year-old woman with a history of multifocal uterine leiomyomas presented
      with left groin pain and was referred for cross-sectional imaging to assess for
      the presence of an inguinal hernia. In this patient, MRI demonstrated a round
      ligament leiomyoma encased in the proximal left inguinal canal. Leiomyomas are
      the most common benign gynecologic tumors, however round ligament leiomyomas are
      very rare. The purpose of this case report is to highlight a rare manifestation
      of a common entity.

PMID- 27875758
TI  - Beyond the lymph nodes: FDG-PET/CT in primary extranodal lymphoma.
AB  - Extranodal lymphoma can be the primary presentation or secondary to systemic
      involvement of lymphoma. 2-(fluorine-18) fluoro-2-deoxy-d-glucose positron
      emission tomography with computer tomography (FDG-PET/CT) is useful in detecting
      extranodal sites during staging, treatment response assessment or recurrence
      detection in patients with lymphoma. In this article, we reviewed the imaging
      features and FDG avidity of primary extranodal lymphoma of various organs and
      systems on FDG-PET/CT, demonstrating the pearls and pitfalls of FDG-PET/CT in
      evaluating this disease entity and cross-referencing to other imaging modalities
      that aid in diagnosis and management.

PMID- 27875760
TI  - Comparing cancer detection rates of patients undergoing short term follow-up vs
      routine follow-up after benign breast biopsies, is follow-up needed?
AB  - PURPOSE: To compare cancer rates after benign breast biopsies between patients
      with short term imaging follow-up (STFU) and those with routine follow-up (RFU).
      MATERIALS & METHODS: Retrospective review of benign stereotactic, US or DCE-MRI
      breast biopsies. RESULTS: Of 580 lesions, 192 (33%) had STFU, and 388 (67%) had
      RFU. For US and mammographic detected lesions, there is no difference in cancer
      rates between the STFU (1 cancer, n=148) and the RFU group (0 cancer, n=365)
      (p=0.29). There were 2 cancers in the STFU group versus 0 in the RFU DCE-MRI
      group (p=0.54). CONCLUSION: Our results support RFU after benign ultrasound and
      stereotactic breast biopsies.

PMID- 27875761
TI  - Prognostic value of post-Yttrium 90 radioembolization therapy 18F
      fluorodeoxyglucose positron emission tomography in patients with liver tumors.
AB  - OBJECTIVE: This study assessed the benefit of post-therapy 18F-FDG PET/CT versus
      CT alone in identifying malignant liver tumor progression following
      radioembolization with Y-90 microspheres. METHODS: 24 patients with 44 liver
      tumors underwent CT imaging pre-radioembolization and PET/CT post
      radioembolization. Predictive value of Response Evaluation Criteria in Solid
      Tumors (RECIST 1.1), The World Health Organization (WHO), mRECIST and European
      Association for the Study of the Liver (EASL) with PET/CT versus CT alone was
      assessed. RESULTS: Prediction of liver malignancy progression was improved
      (p<0.05) for tumors labeled as non-responding based on combined PET/CT with
      RECIST 1.1, WHO, mRECIST, and EASL criteria compared to assessment without PET.
      CONCLUSIONS: The addition of post-therapy PET to routine CT in patients with
      hepatic tumors undergoing radioembolization may improve identification of non
      responding tumors.

PMID- 27875762
TI  - Review of clinical studies and first clinical experiences with a commercially
      available cone-beam breast CT in Europe.
AB  - The dedicated cone-beam breast computed tomography (CBBCT) is a new and promising
      imaging modality which provides isotropic, 3D images of the breast with high
      spatial and contrast resolution. Non-contrast and contrast-enhanced CBBCT (CE
      CBBCT) was superior to mammography for the visualization of breast masses,
      especially in patients with dense breast tissue. CE-CBBCT accurately detects DCIS
      and distinguishes it from benign causes of microcalcifications when compared with
      non-contrast CBBCT and mammography. The purpose of this report is to describe the
      technology and its possible indications, and to present the first results from
      recent clinical studies, illustrating these with our own image examples.

PMID- 27875763
TI  - Production of bio-oil and biochar from soapstock via microwave-assisted co
      catalytic fast pyrolysis.
AB  - In this study, production of bio-oil and biochar from soapstock via microwave
      assisted co-catalytic fast pyrolysis combining the advantages of in-situ and ex
      situ catalysis was performed. The effects of catalyst and pyrolysis temperature
      on product fractional yields and bio-oil chemical compositions were investigated.
      From the perspective of bio-oil yield, the optimal pyrolysis temperature was 550
      degrees C. The use of catalysts reduced the water content, and the addition of
      bentonite increased the bio-oil yield. Up to 84.16wt.% selectivity of
      hydrocarbons in the bio-oil was obtained in the co-catalytic process. In
      addition, the co-catalytic process can reduce the proportion of oxygenates in the
      bio-oil to 15.84wt.% and eliminate the N-containing compounds completely. The
      addition of bentonite enhanced the BET surface area of bio-char. In addition, the
      bio-char removal efficiency of Cd2+ from soapstock pyrolysis in presence of
      bentonite was 27.4wt.% higher than without bentonite.

PMID- 27875764
TI  - Biological pretreatment of sugarcane bagasse with basidiomycetes producing varied
      patterns of biodegradation.
AB  - This work evaluated sugarcane bagasse pretreatment with wood-decay fungi,
      producing varied patterns of biodegradation. The overall mass balance of sugars
      released after pretreatment and enzymatic hydrolysis indicated that a selective
      white-rot was necessary to provide glucose yields similar to the ones observed
      from leading physico-chemical pretreatment technologies. The selective white-rot
      Ceriporiopsis subvermispora was selective for lignin degradation in the
      lignocellulosic material, preserved most of the glucan fraction, and increased
      the cellulose digestibility of biotreated material. Glucose mass balances
      indicated that of the potential glucose of untreated bagasse, 47% was recovered
      as sugar-rich syrup after C. subvermispora biotreatment for 60days followed by
      enzymatic digestion of the pretreated material.

PMID- 27875765
TI  - The dynamic changes and interactional networks of prokaryotic community between
      co-digestion and mono-digestions of corn stalk and pig manure.
AB  - Anaerobic co-digestion is considered to be an efficient way to improve the biogas
      production. The abundance, dynamic and interactional networks of prokaryotic
      community were investigated between co-digestion and mono-digestions of corn
      stalk and pig manure in mesophilic batch test. Co-digestion showed higher methane
      production, and contributed to suitable microenvironment as well as stable
      prokaryotic community structure. The highest methane production was achieved with
      the highest relative abundance of Methanosaeta. Prokaryotic community in mono
      digestions might inhibited by FA or FVFA. The functional modules in co-digestion
      and mono-digestion of pig manure clustered together with bigger size and higher
      degree, and the connections of metabolic functions were better-organized, which
      means high-efficient utilization of substrate and prevention of the two digestion
      systems crash. The partial mantel tests showed the functional modules were
      significantly affected by environmental factors. These results further explained
      that why co-digestion was more efficient than mono-digestion owing to suitable
      microenvironment.

PMID- 27875766
TI  - Augmentation of bacterial homeostasis by regulating in situ buffer capacity:
      Significance of total dissolved salts over acidogenic metabolism.
AB  - During anaerobic fermentation, consequent accumulation of acidic fermented
      products leads to the failure of pH homeostasis. The present study aimed to
      comprehend the changes in buffering capacity with addition of sodium salts of
      hydroxide, bicarbonate and phosphate. The results showed notable augmentation in
      buffer capacity and cumulative hydrogen production (CHP) compared to control. The
      influential factor is the amount of undissociated volatile fatty acids released
      that affected the cell metabolism and consequently biohydrogen generation. It is
      inferred that among the tested salts, sodium bicarbonate has substantial
      buffering capacity (beta, 0.035+/- mol) ensuing maximum CHP (468+/- mL). Besides,
      bioelectrochemical analysis revealed variations in redox currents that aligned
      with biohydrogen production. The study provides valuable information on the role
      of inorganic dissolved salts that would be required to regulate H2 generation and
      acidogenesis in the aspects of acid-gas phase system.

PMID- 27875768
TI  - High efficiency succinic acid production from glycerol via in situ fibrous bed
      bioreactor with an engineered Yarrowia lipolytica.
AB  - In this study, in situ fibrous bed bioreactor (isFBB) was developed at the first
      time for efficient succinic acid (SA) production by Yarrowia lipolytica. After
      optimization, SA titer, productivity and yield of 51.9g/L, 1.46g/L/h and 0.42g/g
      were obtained respectively via isFBB fermentation under conditions of 750cm2
      cotton towel, 120g/L initial glycerol and 3L/min aeration rate. By fed batch
      strategy, SA titer raised up to 198.2g/L was achieved, which was the highest
      value ever reported. In operation stability study, SA productivity showed no
      obvious decrease after 12 repeated batches of 460h fermentation, and cell
      viability even recovered within two repeated batches after intentional
      interruption. This study successfully attained a highly efficient and stable
      isFBB for enhanced SA production by Y. lipolytica.

PMID- 27875767
TI  - Enhanced bioelectricity generation and azo dye treatment in a reversible photo
      bioelectrochemical cell by using novel anthraquinone-2,6-disulfonate (AQDS)/MnOx
      doped polypyrrole film electrodes.
AB  - A novel anthraquinone-2,6-disulfonate/MnOx-doped polypyrrole film (AQDS/Mn/PPy)
      electrode was prepared by one-step electropolymerization method and was used to
      improve performance of a reversible photo-bioelectrochemical cell (RPBEC). The
      RPBEC was operated in polarity reversion depended on dark/light reaction of alga
      Chlorella vulgaris by which sequential decolorization of azo dye and
      mineralization of decolorization products coupled with bioelectricity generation
      can be achieved. The results showed that formation of uniform AQDS/Mn/PPy film
      significantly enhanced electroactive surface area and electrocatalytic activity
      of carbon electrode. The RPBEC with AQDS/Mn/PPy electrodes demonstrated 77%
      increases in maximum power and 73% increases in Congo red decolorization rate
      before polarity reversion, and 198% increases in maximum power and 138% increases
      in decolorization products mineralization rate after polarity reversion,
      respectively, compared to the RPBEC with bare electrode. This was resulted from
      simultaneous dynamics improvement in half-reaction rate of anode and photo
      biocathode due to enhanced electron transfer and algal-bacterial biofilm
      formation.

PMID- 27875769
TI  - Status epilepticus in pregnant women with epilepsy after valproate adjustment: A
      case series.
AB  - PURPOSE: Valproate is an effective wide-spectrum anti-epileptic drug that is also
      known to be teratogenic. Its administration in epileptic women remains
      controversial. This report aims to draw more attention to valproate adjustment
      before and during pregnancy. METHODS: We collected medical records of pregnant
      women with epilepsy at West China Hospital in Chengdu, China who developed status
      epilepticus during pregnancy after valproate withdrawal or reduction in dose from
      January 2013 to July 2015. RESULTS: A total of 281 pregnancies in patients with
      epilepsy were examined; 6 episodes of status epilepticus occurred during these
      pregnancies. Four patients with status epilepticus took long-term valproate
      before pregnancy. Among them, 2 patients stopped taking valproate 3 months prior
      to pregnancy, and 2 patients discontinued valproate or reduced their valproate
      dose when pregnancy was confirmed. All 4 suffered from a convulsive status
      epilepticus; 3 experienced an increased frequency of seizures. One child was
      diagnosed with neonatal asphyxia, hypoxic-ischemic encephalopathy, and neonatal
      pneumonia. CONCLUSION: Valproate adjustment prior to or during pregnancy may
      result in deterioration of seizure control, which may include resultant status
      epilepticus. Valproate during pregnancy increases the risk of major congenital
      malformations, but the significance of maintaining seizure control in pregnant
      women should be also taken into consideration. Open and careful discussion with
      every pregnant woman with epilepsy should discuss the risk-benefit ratio of
      epilepsy medications.

PMID- 27875770
TI  - Evaluation of permeable pavement responses to urban surface runoff.
AB  - The construction of permeable pavement (PP) in sidewalks of urban areas is an
      alternative low impact development (LID) to control stormwater runoff volume and
      consequently decrease the discharge of pollutants in receiving water bodies. In
      this paper, some laboratory experiments were performed to evaluate the efficiency
      of a PP subjected to sediment loadings during its life span. Simple infiltration
      models were validated by the laboratory experiments to evaluate the trend and
      extend of PP infiltration capacity throughout the life of the pavement operation.
      In addition, performances of the PP in removing total suspended solids (TSS) and
      selective nutrient pollutants such as NO3-,NH4+ and PO4-3 from the surface runoff
      have been investigated. Experimental data showed that the PP was completely
      clogged after seven hydrological years. The model revealed that the ratio of
      horizontal to vertical hydraulic conductivity is 3.5 for this PP. Moreover, it
      was found that 20% reduction in hydraulic conductivity occurred after three
      hydrological years. The PP showed 100%, 23% and 59% efficiencies in sediment
      retention (TSS removal), (PO4-3), and N-NH4+ removal during the entire study,
      respectively. However, the removal efficiency of (N-NO3-) was -12% and we suspect
      the increase in effluent (N-NO3-) is due to the nitrification process in
      subsurface layers. This study demonstrated that when PPs are annually cleaned, it
      is expected that PPs can function hydraulically and be able to remove particulate
      pollutants during their life span by a proper maintenance.

PMID- 27875771
TI  - Nemo-like kinase 1 (Nlk1) and paraxial protocadherin (PAPC) cooperatively control
      Xenopus gastrulation through regulation of Wnt/planar cell polarity (PCP)
      signaling.
AB  - The Wnt/planar cell polarity (PCP) pathway directs cell migration during
      vertebrate gastrulation and is essential for proper embryonic development.
      Paraxial protocadherin (PAPC, Gene Symbol pcdh8.2) is an important activator of
      Wnt/PCP signaling during Xenopus gastrulation, but how PAPC activity is
      controlled is incompletely understood. Here we show that Nemo-like kinase 1
      (Nlk1), an atypical mitogen-activated protein (MAP) kinase, physically associates
      with the C-terminus of PAPC. This interaction mutually stabilizes both proteins
      by inhibiting polyubiquitination. The Nlk1 mediated stabilization of PAPC is
      essential for Wnt/PCP signaling, tissue separation and gastrulation movements. We
      identified two conserved putative phosphorylation sites in the PAPC C-terminus
      that are critical for Nlk1 mediated PAPC stabilization and Wnt/PCP regulation.
      Intriguingly, the kinase activity of Nlk1 itself was not essential for its
      cooperation with PAPC, suggesting an indirect regulation for example by impeding
      a different kinase that promotes protein degradation. Overall these results
      outline a novel, kinase independent role of Nlk1, wherein Nlk1 regulates PAPC
      stabilization and thereby controls gastrulation movements and Wnt/PCP signaling
      during development.

PMID- 27875773
TI  - Bereitschaftspotential preceding spontaneous and voluntary eyelid blinks in
      normal individuals.
AB  - OBJECTIVE: To investigate the Bereitschaftspotential (BP) preceding spontaneous
      and voluntary eyelid blinks in normal subjects. METHODS: Eighteen healthy
      individuals (10 female) between 17 and 60years (mean 35) were studied. The EEG
      was recorded from 11 scalp positions of the 10-20 international electrode
      placement system referenced to linked mastoids. The vertical electrooculogram
      (VEOG) was recorded from two electrodes positioned above and below the right eye.
      The ground electrode was placed in the right clavicle. The recordings were
      obtained during spontaneous and voluntary eyelid blinks. Two-second EEG segments
      before the onset of the blink potential (visually identified at the VEOG channel)
      were averaged and analyzed off-line. The statistical significance of differences
      was evaluated by repeated-measures analysis of variance with Geisser-Greenhouse
      correction for violation of sphericity and the Newman-Keuls test was used for
      post hoc comparisons. RESULTS: A BP starting around -1700ms prior to the onset of
      voluntary blink was observed; it had average amplitude in the negative peak of
      3.3MUV. There was no BP preceding spontaneous blinking. CONCLUSION: A BP precedes
      voluntary blinks but not spontaneous blinks. SIGNIFICANCE: This is the first
      study evaluating the BP preceding spontaneous and voluntary eye blinks.

PMID- 27875772
TI  - Hnf4alpha is a key gene that can generate columnar metaplasia in oesophageal
      epithelium.
AB  - Barrett's metaplasia is the only known morphological precursor to oesophageal
      adenocarcinoma and is characterized by replacement of stratified squamous
      epithelium by columnar epithelium. The cell of origin is uncertain and the
      molecular mechanisms responsible for the change in cellular phenotype are poorly
      understood. We therefore explored the role of two transcription factors, Cdx2 and
      HNF4alpha in the conversion using primary organ cultures. Biopsy samples from
      cases of human Barrett's metaplasia were analysed for the presence of CDX2 and
      HNF4alpha. A new organ culture system for adult murine oesophagus is described.
      Using this, Cdx2 and HNF4alpha were ectopically expressed by adenoviral
      infection. The phenotype following infection was determined by a combination of
      PCR, immunohistochemical and morphological analyses. We demonstrate the
      expression of CDX2 and HNF4alpha in human biopsy samples. Our oesophageal organ
      culture system expressed markers characteristic of the normal SSQE: p63, K14, K4
      and loricrin. Ectopic expression of HNF4alpha, but not of Cdx2 induced expression
      of Tff3, villin, K8 and E-cadherin. HNF4alpha is sufficient to induce a columnar
      like phenotype in adult mouse oesophageal epithelium and is present in the human
      condition. These data suggest that induction of HNF4alpha is a key early step in
      the formation of Barrett's metaplasia and are consistent with an origin of
      Barrett's metaplasia from the oesophageal epithelium.

PMID- 27875774
TI  - Risk factors for acute kidney injury in critically ill patients with complicated
      intra-abdominal infection.
AB  - PURPOSE: The aim was to determine the factors related to acute kidney injury
      (AKI) in surgical septic patients with complicated intra-abdominal infection
      (CIAI) and mortality associated to AKI. METHODS: An observational study was
      performed in patients with CIAI requiring surgery and ICU admission (June 2011
      June 2013). Factors at admission associated with developing of AKI and renal
      replacement therapy (RRT) and association between mortality and AKI and RRT were
      studied. RESULTS: A total of 114 patients were included. Developing of AKI was
      independently associated with the sequential organ failure assessment (SOFA)
      score (odds ratio [OR], 1.570; 95% confidence interval [CI], 1.286-2.016) and
      creatinine at admission (OR for 0.1 units, 1.560; 95% CI, 1.296-1.990). Renal
      replacement therapy was independently associated with arterial hypertension (OR,
      4.896; 95% CI, 1.501-15.971) and SOFA (OR, 1.713; 95% CI, 1.377-2.132). In
      another model with more predictive capacity, the number of previous medications
      that may alter renal function (OR, 3.732; 95% CI, 1.923-8.383) and SOFA (OR,
      1.860; 95% CI, 1.469-2.541) were related to RRT. Both AKI and RRT were related to
      intensive care unit (P=.014 and P<.001, respectively) and 28-day mortality
      (P=.045 and P<.001, respectively). CONCLUSIONS: Acute kidney injury in patients
      with CIAI is clearly associated with SOFA and creatinine at admission. Severe AKI
      with RRT need is highly associated with both previous arterial hypertension and
      the number of previous medications potentially affecting renal function.

PMID- 27875775
TI  - Bronchoscopic intubation is an effective airway strategy in critically ill
      patients.
AB  - PURPOSE: American Society of Anesthesiologists guidelines recommend the use of
      bronchoscopic intubation as a rescue technique in critically ill patients. We
      sought to assess the safety and efficacy of bronchoscopic intubation as an
      initial approach in critically ill patients. METHODS: We performed a
      retrospective cohort study of patients who underwent endotracheal intubation in
      the medical intensive care unit of a tertiary urban referral center over 1
      academic year. The primary outcome was first-pass success rate. MEASUREMENTS AND
      MAIN RESULTS: We identified 219 patients who underwent either bronchoscopic
      (n=52) or laryngoscopic guided (n=167) intubation as the initial attempt. There
      was a higher first-pass success rate in the bronchoscopic intubation group than
      in the laryngoscopic group (96% vs 78%; P=.003). The bronchoscopic intubation
      group had a higher body mass index (28.4 vs 25.9; P=.027) and higher
      preintubation fraction of inspired oxygen requirement (0.73+/-0.27 vs 0.63+/
      0.30; P=.044) than the laryngoscopic group. There were no cases of right mainstem
      intubation, esophageal intubation, or pneumothorax with bronchoscopic intubation.
      Rates of postintubation hypotension and hypoxemia were similar in both groups.
      The association with first-pass success remained with multivariate and propensity
      matched analysis. CONCLUSIONS: Bronchoscopic intubation as an initial strategy in
      critically ill patients is associated with a higher first-pass success rate than
      laryngoscopic intubation, and is not associated with an increase in
      complications.

PMID- 27875776
TI  - Symbiosis with AMF and leaf Pi supply increases water deficit tolerance of woody
      species from seasonal dry tropical forest.
AB  - In seasonal dry tropical forests, plants are subjected to severe water deficit,
      and the arbuscular mycorrhizal fungi (AMF) or inorganic phosphorus supply (Pi)
      can mitigate the effects of water deficit. This study aimed to assess the
      physiological performance of Poincianella pyramidalis subjected to water deficit
      in combination with arbuscular mycorrhizal fungi (AMF) and leaf inorganic
      phosphorus (Pi) supply. The experiment was conducted in a factorial arrangement
      of 2 water levels (+H2O and -H2O), 2 AMF levels (+AMF and -AMF) and 2Pi levels
      (+Pi and -Pi). Leaf primary metabolism, dry shoot biomass and leaf mineral
      nutrients were evaluated. Inoculated AMF plants under well-watered and drought
      conditions had higher photosynthesis and higher shoot biomass. Under drought,
      AMF, Pi or AMF+Pi plants showed metabolic improvements in photosynthesis, leaf
      biochemistry and higher biomass compared to the plants under water deficit
      without AMF or Pi. After rehydration, those plants submitted to drought with AMF,
      Pi or AMF+Pi showed a faster recovery of photosynthesis compared to treatment
      under water deficit without AMF or Pi. However, plants under the drought
      condition with AMF showed a higher net photosynthesis rate. These findings
      suggest that AMF, Pi or AMF+Pi increase the drought tolerance in P. pyramidalis,
      and AMF associations under well-watered conditions increase shoot biomass and,
      under drought, promoted faster recovery of photosynthesis.

PMID- 27875777
TI  - Does pelvic floor muscle contraction early after delivery cause perineal pain in
      postpartum women?
AB  - OBJECTIVE: Pelvic floor muscle training is effective and necessary in the
      prevention and treatment of pelvic floor dysfunction during pregnancy and after
      childbirth. But because of the high prevalence of perineal pain observed in women
      after childbirth, many women and caregivers fear to start pelvic floor muscle
      training immediately after childbirth. However, it is unknown whether pelvic
      floor muscle contractions (PFMC) provoke perineal pain in women shortly after
      childbirth. Therefore, the main objective is to study whether PFMC performed
      immediately after childbirth is painful or not. STUDY DESIGN: Observational
      longitudinal study. Perineal pain was assessed (1-6 days and 9 weeks postpartum)
      using a visual analogue scale (VAS 0-10) during PFMC and during several
      activities of daily living (ADL), during micturition and defecation. Descriptive
      statistics, Wilcoxon and McNemar tests were used. RESULTS: A total of 233 women
      participated (148 primiparous and 85 multiparous). Immediately postpartum the
      prevalence and intensity of pain during ADL (73%; VAS 4.9 (+/-2.3)), micturition
      (47%; VAS 3.4 (+/-1.7)) and defecation (19%; VAS 3.6 (+/-2.2)) were significantly
      higher (all p<0.000) than during PFMC (8%; VAS 2.2 (+/-0.9)). At 9 weeks
      postpartum, 30% experienced perineal pain during sexual intercourse (VAS 4.6 +/-
      2.3) and 18% during defecation (VAS 4.7 +/- 2.3), but none during PFMC.
      CONCLUSION: Perineal pain is highly prevalent immediately after childbirth during
      ADL, micturition and defecation, but not during PFMC (only 8%). In case perineal
      pain occurs during PFMC, the intensity of pain is low (VAS 2). These results show
      that fear of perineal pain should not discourage women to start pelvic floor
      muscle training shortly after childbirth.

PMID- 27875778
TI  - Phytochrome-interacting factor from Arabidopsis to liverwort.
AB  - Phytochromes are red and far-red light photoreceptors that regulate the responses
      of plants to light throughout their life cycles. Phytochromes do this in part by
      inhibiting the function of a group of basic helix-loop-helix transcription
      factors called phytochrome-interacting factors (PIFs). Arabidopsis has eight PIFs
      that function sometimes redundantly and sometimes distinctively depending on
      their expression patterns and protein stability, as well as on variations in the
      promoters they target in vivo. PIF-like proteins exist in other seed plants and
      non-vascular plants where they also regulate light responses. The mechanism by
      which phytochrome regulates light responses by promoting the degradation of the
      PIFs is conserved in liverwort, suggesting it must have evolved some time before
      the last common ancestor shared by seed plants and non-vascular plants.

PMID- 27875780
TI  - VP1 residues around the five-fold axis of enterovirus A71 mediate heparan sulfate
      interaction.
AB  - Enterovirus A71 (EV-A71) is a neurotropic enterovirus that uses heparan sulfate
      as an attachment receptor. The molecular determinants of EV-A71-heparan sulfate
      interaction are unknown. With In silico heparin docking and mutagenesis of all
      possible lysine residues in VP1, we identified that K162, K242 and K244 are
      responsible for heparin interaction and inhibition. EV-A71 mutants with K242A and
      K244A rapidly acquired compensatory mutations, T100K or E98A, and Q145R-T237N
      respectively, which restored the heparin-binding phenotype. Both VP1-98 and VP1
      145 modulates heparin binding. Heparin-binding phenotype was completely abolished
      with VP1-E98-E145, but was restored by an E98K or E145Q substitution. During cell
      culture adaptation, EV-A71 rapidly acquired K98 or Q/G145 to restore the heparin
      binding phenotype. Together with next-generation sequencing analysis, our results
      implied that EV-A71 has high genetic plasticity by modulating positively-charged
      residues at the five-fold axis during in vitro heparin adaptation. Our finding
      has impact on EV-A71 vaccine production, evolutionary studies and pathogenesis.

PMID- 27875779
TI  - Novel pyrimidine-2,4-dione-1,2,3-triazole and furo[2,3-d]pyrimidine-2-one-1,2,3
      triazole hybrids as potential anti-cancer agents: Synthesis, computational and X
      ray analysis and biological evaluation.
AB  - Regioselective 1,4-disubstituted 1,2,3-triazole tethered pyrimidine-2,4-dione
      derivatives (5-23) were successfully prepared by the copper(I)-catalyzed click
      chemistry. While known palladium/copper-cocatalyzed method based on Sonogashira
      cross-coupling followed by the intramolecular 5-endo-dig ring closure generated
      novel 6-alkylfuro[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids (24b-37b), a
      small library of their 5-alkylethynyl analogs (24a-37a) was synthesized and
      described for the first time by tandem terminal alkyne dimerization and
      subsequent 5-endo-trig cyclization, which was additionally corroborated with
      computational and X-ray crystal structure analyses. The nature of substituents on
      alkynes and thereof homocoupled 1,3-diynes predominantly influenced the ratio of
      the formed products in both pathways. In vitro antiproliferative activity of
      prepared compounds evaluated on five human cancer cell lines revealed that N,N
      1,3-bis-(1,2,3-triazole)-5-bromouracil (5-7) and 5,6-disubstituted furo[2,3
      d]pyrimidine-2-one-1,2,3-triazole 34a hybrids exhibited the most pronounced
      cytostatic acitivities against hepatocellular carcinoma (HepG2) and cervical
      carcinoma (HeLa) cells with higher potencies than the reference drug 5
      fluorouracil. Cytostatic effect of pyrimidine-2,4-dione-1,2,3-triazole hybrid 7
      in HepG2 cells could be attributed to the Wee-1 kinase inhibition and abolishment
      of sphingolipid signaling mediated by acid ceramidase and sphingosine kinase 1.
      Importantly, this compound proved to be a non-mitochondrial toxicant, which makes
      it a promising candidate for further lead optimization and development of a new
      and more efficient agent for the treatment of hepatocellular carcinoma.

PMID- 27875781
TI  - Long-term pediatrician outcomes of a parent led curriculum in developmental
      disabilities.
AB  - : Previous research has demonstrated high satisfaction and perceived relevance of
      Project DOCC (Delivery of Chronic Care), a parent led curriculum in developmental
      disabilities, across a sample of medical residents. AIMS: The influence of such a
      training program on the clinical practices and professional activities of these
      residents once they are established in their careers as physicians, however, has
      not been studied; this was the aim of the present study. METHODS: An anonymous
      follow-up survey was designed and disseminated to physicians who participated in
      Project DOCC during their one-month developmental disabilities rotation as part
      of their pediatrics or medicine/pediatric residency between 2002 and 2010. Fifty
      eight physicians completed the survey. RESULTS: The findings suggest that
      participation in a parent led curriculum during medical residency had a lasting
      impact on physicians' relationships with families. Specifically, a majority of
      the physicians espoused a family-centered approach to care, a sensitivity to the
      interactional effect that caring for a Child with Special Health Care Needs
      (CSHCN) has on family members, the need for physicians to have a prominent role
      in community resource coordination, and the importance of an integrated approach
      to health care provision. CONCLUSIONS: Use of a parent led curriculum as a means
      to increase the provision of family-centered care by physicians is supported.

PMID- 27875782
TI  - Using the concrete-representational-abstract approach to support students with
      intellectual disability to solve change-making problems.
AB  - BACKGROUND/AIMS/METHODS: The Concrete-Representational-Abstract (CRA)
      instructional approach supports students with disabilities in mathematics. Yet,
      no research explores the use of the CRA approach to teach functional-based
      mathematics for this population and limited research explores the CRA approach
      for students who have a disability different from a learning disability, such as
      an intellectual disability. This study investigated the effects of using the CRA
      approach to teach middle school students in a self-contained mathematics class
      focused on functional-based mathematics to solve making change problems.
      Researchers used a multiple probe across participants design to determine if a
      functional relation existed between the CRA strategy and students' ability to
      solve making change problems. PROCEDURES/OUTCOMES: The study of consisted of five
      to-eight baseline sessions, 9-11 intervention sessions, and two maintenance
      sessions for each student. Data were collected on percentage of making change
      problems students solved correctly. RESULTS/CONCLUSIONS: The CRA instructional
      strategy was effective in teaching all four participants to correctly solve the
      problems; a functional relation between the CRA approach and solving making
      change with coins problems across all participants was found. IMPLICATIONS: The
      CRA instructional approach can be used to support students with mild intellectual
      disability or severe learning disabilities in learning functional-based
      mathematics, such as purchasing skills (i.e., making change).

PMID- 27875783
TI  - PRAME overexpression predicted good outcome in pediatric B-cell acute
      lymphoblastic leukemia patients receiving chemotherapy.
AB  - To investigate the prognostic value of PRAME expression in pediatric acute
      lymphoblastic leukemia(ALL), we measured PRAME transcript levels at diagnosis in
      191 patients(146 B-ALL; 45T-ALL)receiving chemotherapy only. PRAME overexpression
      was defined as transcript levels higher than 0.30%, which is the upper limit of
      normal bone marrow and the optimal cutoff value derived from ROC curve analysis.
      PRAME overexpression was identified in 45.5% of patients. In B-ALL, PRAME
      overexpression was significantly associated with lower CIR(cumulative incidence
      of relapse), higher DFS (disease-freesurvival), and OS(overall survival) rates at
      3 years, respectively (5.8% vs. 14.9%, P=0.014; 94.2% vs. 85.1%, P=0.014; 96.0%
      vs. 87.4%, P=0.039). PRAME overexpression had no impact on outcome in T-ALL
      patients. Among B-ALL patients with non-poor cytogenetic risk, those with PRAME
      overexpression showed significantly lower CIR, higher DFS and OS rates at 3
      years, respectively (8.47% vs. 14.5%, P=0.009; 96.5% vs. 85.5%, P=0.009; 98.4%
      vs. 88.0%, P=0.023). Furthermore, PRAME overexpression was an independent good
      prognostic factor for relapse in all B-ALL patients and B-ALL patients with non
      poor cytogenetic risk. Therefore, the prognostic significance of PRAME
      overexpression differed by ALL subtype; It predicted good outcome in pediatric B
      ALL receiving chemotherapy.

PMID- 27875784
TI  - Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures
      in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors.
AB  - Dextrometrophan (DM), widely used as an antitussive, has recently generated
      interest as an anticonvulsant drug. Some effects of dextrometrophan are
      associated with alterations in several pathways, such as inhibition of nitric
      oxide synthase (NOS) enzyme and N-methyl d-aspartate (NMDA) receptors. In this
      study, we aimed to investigate the anticonvulsant effect of acute administration
      of dextrometrophan on pentylenetetrazole (PTZ)-induced seizures and the probable
      involvement of the nitric oxide (NO) pathway and NMDA receptors in this effect.
      For this purpose, seizures were induced by intravenous PTZ infusion. All drugs
      were administrated by intraperitoneal (i.p.) route before PTZ injection. Our
      results demonstrate that acute DM treatment (10-100mg/kg) increased the seizure
      threshold. In addition, the nonselective NOS inhibitor L-NAME (10mg/kg) and the
      neural NOS inhibitor, 7-nitroindazole (40mg/kg), at doses that had no effect on
      seizure threshold, augmented the anticonvulsant effect of DM (3mg/kg), while the
      inducible NOS inhibitor, aminoguanidine (100mg/kg), did not affect the
      anticonvulsant effect of DM. Moreover, the NOS substrate l-arginine (60mg/kg)
      blunted the anticonvulsant effect of DM (100mg/kg). Also, NMDA antagonists,
      ketamine (0.5mg/kg) and MK-801 (0.05mg/kg), augmented the anticonvulsant effect
      of DM (3mg/kg). In conclusion, we demonstrated that the anticonvulsant effect of
      DM is mediated by a decline in neural nitric oxide activity and inhibition of
      NMDA receptors.

PMID- 27875785
TI  - Manual asymmetries in bimanual isochronous tapping tasks in children.
AB  - Tapping tasks have been investigated throughout the years, with variations in
      features such as the complexity of the task, the use of one or both hands, the
      employ of auditory or visual stimuli, and the characteristics of the subjects.
      The evaluation of lateral asymmetries in tapping tasks in children offers an
      insight into the structure of rhythmic movements and handedness at early stages
      of development. The current study aims to investigate the ability of children
      (aged six and seven years-old) to maintain a rhythm, in a bimanual tapping task
      at two different target frequencies, as well as the manual asymmetries displayed
      while doing so. The analyzed data in this work are the series of the time
      intervals between successive taps. We suggest several profiles of behavior,
      regarding the overall performance of children in both tempo conditions. We also
      propose a new method of quantifying the variability of the performance and the
      asymmetry of the hands, based on ellipses placed on scatter plots of the non
      dominant-dominant series versus the dominant-non-dominant series. We then use
      running correlations to identify changes of coordination tendencies over time.
      The main results show that variability is larger in the task with the longer
      target interval. Furthermore, most children evidence lateral asymmetries, but in
      general they show the capacity to maintain the mean of consecutive intertap
      intervals of both hands close to the target interval. Finally, we try to
      interpret our findings in the light of existing models and timing modes.

PMID- 27875786
TI  - Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer.
AB  - Obesity is associated with an increased risk of estrogen-dependent breast cancer
      after menopause. Adipose tissue undergoes important changes in obesity due to
      excess storage of lipids, leading to adipocyte cell death and the recruitment of
      macrophages. The resultant state of chronic low-grade inflammation is associated
      with the activation of NFkB signaling and elevated levels of aromatase, the rate
      limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral
      and subcutaneous fat, but also in the breast fat. The regulation of aromatase in
      the breast adipose stromal cell in response to inflammatory mediators is under
      the control of complex signaling pathways, including metabolic pathways involving
      LKB1/AMPK, p53, HIF1alpha and PKM2. Interventions aimed at modifying weight,
      including diet and exercise, are associated with changes in adipose tissue
      inflammation and estrogen production that are likely to impact breast cancer
      risk. This review will present an overview of these topics.

PMID- 27875787
TI  - Simultaneous determination of anemoside B4, phellodendrine, berberine, palmatine,
      obakunone, esculin, esculetin in rat plasma by UPLC-ESI-MS/MS and its application
      to a comparative pharmacokinetic study in normal and ulcerative colitis rats.
AB  - A sensitive and rapid ultra-performance liquid chromatography-electrospray
      ionization-mass spectrometry (UPLC-ESI-MS/MS) method was developed for the
      simultaneous analysis of anemoside B4, phellodendrine, berberine, palmatine,
      obakunone, esculin, esculetin, toosendanin (IS1 of anemoside B4),
      tetrahydropalmatine (IS2 of phellodendrine, berberine, palmatine and obakunone)
      and scopoletin (IS3 of esculin and esculetin) and to compare the pharmacokinetics
      of these active ingredients in normal and ulcerative colitis rats. After methanol
      deproteinization, solvents were evaporated at 40 degrees C under a gentle stream
      of nitrogen. Chromatography was performed using a C18 column with a gradient
      elution of 0.1% aqueous formic acid and acetonitrile at 0.4ml/min. Detection and
      measurement were performed on a 4000 QTRAP UPLC-MS/MS system from AB Sciex in the
      multiple reaction monitoring (MRM) mode. Phellodendrine, berberine, palmatine,
      obakunone, esculin, esculetin, tetrahydropalmatine (IS2) and scopoletin (IS3)
      were monitored under positive ionization conditions. Anemoside B4, and
      toosendanin (IS1) were monitored under negative ionization conditions. The
      optimized mass transition ion-pairs (m/z) were 1221.1/750.7 for anemoside B4,
      343.2/193.2 for phellodendrine, 337.1/321.0 for berberine, 353.0/336.9 for
      palmatine, 455.1/161.1 for obakunone, 341.2/179.2 for esculin, 179.1/123.0 for
      esculetin, 573.4/531.4 for toosendanin (IS1), 356.2/192.2 for tetrahydropalmatine
      (IS2) and 193.0/133.1 for scopoletin (IS3).

PMID- 27875789
TI  - Comparison of the chemical consituents and immunomodulatory activity of
      ophiopogonis radix from two different producing areas.
AB  - Zhemaidong (ZMD) and Chuanmaidong (CMD) are the two genuine cultivation areas of
      Ophiopogonis Radix which has been widely used as a traditional Chinese medicine
      in China for treating cardiovascular and pulmonary diseases. Differences between
      ZMD and CMD in chemical constituents and pharmacological effects have been
      reported, however, the details remain largely unknown. The aim of this study was
      to comprehensively characterize the chemical composition of Ophiopogonis Radix
      from the two producing areas and compare their immunomodulatory activities. An
      approach of HPLC-MS coupled with multivariate statistical analysis was
      established to reveal the characteristic constituents of ZMD and CMD.
      Furthermore, the effects of ZMD and CMD on the macrophage phagocytosis and
      gastrointestinal peristalsis were also determined in zebrafish models for
      assessing the immunomodulatory activities of these two strains. The results
      revealed that the chemical constituents of ZMD and CMD were much different from
      each other, and 19 constituents could be served as chemical markers to
      distinguish these two strains. Moreover, ZMD showed higher promoting rates in
      macrophage phagocytosis and gastrointestinal motility than those of CMD,
      suggesting ZMD might possess better immunomodulatory activities. Taken together,
      the results generated from this study indicated that the herbs from different
      producing areas should be evaluated and considered in preparing TCM
      prescriptions.

PMID- 27875788
TI  - Simultaneous determination and pharmacokinetic study of four phenolic acids in
      rat plasma using UFLC-MS/MS after intravenous administration of salvianolic acid
      for injection.
AB  - A simple, sensitive and selective ultra-fast liquid chromatography-tandem mass
      spectrometry (UFLC-MS/MS) method was established for simultaneous determination
      and pharmacokinetic study of rosmarinic acid (RA), salvianolic acid D (Sal D),
      lithospermic acid (LA) and salvianolic acid B (Sal B) in rat plasma after
      intravenous administration of salvianolic acid for injection (SAFI). Three doses
      of administration, containing 14, 28 and 56mg/kg, were investigated in this
      study. Plasma samples were pretreated using protein precipitation (PP) with pre
      cooled acetonitrile. Chromatographic separation was achieved on a CORTECSTM UPLC
      C18 column (1.6MUm, 2.1*100mm) with a mobile phase composed of 0.1% formic acid
      aqueous (V/V) and 0.1% formic acid acetonitrile (V/V). Analytes were detected
      using electrospray ionization (ESI) source in negative ionization mode and
      quantified in multiple reaction monitoring (MRM) mode. The validated method is
      stable and reliable. No significant difference of half lives (t1/2) of four
      analytes at three doses was observed. Area under the curve (AUC0-infinity) and
      peak concentration (Cmax) of the four analytes demonstrated a linear increase in
      across the doses with the linear correlation r of each analyte at three doses
      were greater than 0.95. It indicated that the pharmacokinetic behavior of SAFI is
      positively related to dose at the range of 14-56mg/kg.

PMID- 27875790
TI  - Vaping to lose weight: Predictors of adult e-cigarette use for weight loss or
      control.
AB  - INTRODUCTION: Some traditional cigarette smokers are motivated to smoke to lose
      weight or control their weight. The current study evaluated whether a subset of
      adult e-cigarette users reported vaping to lose or control their weight and
      examined potential predictors of vaping for weight management. METHODS: Adult e
      cigarette users (n=459) who reported wanting to lose weight or maintain their
      weight completed an anonymous online survey. Participants reported on
      demographics, vaping frequency, e-cigarette nicotine content, cigarette smoking
      status, preferred e-cigarette/e-liquid flavors, current weight status (i.e.,
      overweight, underweight), use of dieting strategies associated with anorexia and
      bulimia, lifetime history of binge eating, self-discipline, and impulse control.
      Binary logistic regression was used to examine whether vaping for weight
      loss/control was associated with the aforementioned variables. RESULTS:
      Participants who reported vaping for weight loss/control (13.5%) were more likely
      to vape frequently (adjOR=1.15; 95% CI [1.00, 1.31]); be overweight (adjOR=2.80;
      [1.33, 5.90]); restrict calories (adjOR=2.23; [1.13, 4.42]); have poor impulse
      control (adjOR=0.59; [0.41, 0.86]); and prefer coffee- (adjOR=2.92; [1.47, 5.80])
      or vanilla-flavored e-liquid (adjOR=7.44; [1.56, 36.08]). CONCLUSIONS: A subset
      of adult e-cigarette users reported vaping for weight loss/control, raising
      concerns about expanded, scientifically unsubstantiated uses of e-cigarettes.
      Identifying where individuals obtain information about vaping for weight loss
      (e.g., e-cigarette ads, Internet) and whether weight-related motives promote e
      cigarette initiation among e-cigarette naive individuals is important to
      informing regulatory efforts. Further research also is needed to better
      understand the link between e-liquid flavors and weight loss motivations.

PMID- 27875791
TI  - Localization and expression patterns of TRP channels in submandibular gland
      development.
AB  - OBJECTIVE: Expression of Transient receptor potential (TRP) channels: TRP
      canonical (TRPC)1, TRP vanilloid (TRPV)3, TRPV4 and TRP melastatin (TRPM)8 in
      adult rat salivary gland has recently been reported. The authors investigated
      expression of these TRP channels in the submandibular gland during early
      developmental stage in which the cell constitution is different, and discussed
      the function of TRP in the submandibular gland in early development. DESIGN:
      Using rat submandibular gland at embryonic days (E)18 and E20 and postnatal days
      (PN)0 and PN5 and PN28, expression of TRPV3, TRPV4, TRPC1 and TRPM8 was
      investigated using real-time polymerase chain reaction (RT-PCR) and
      immunohistochemistry. RESULTS: All TRP channels were expressed in cells
      constituting the submandibular gland in early developmental stage, but an
      increase in the expression level at PN5 on RT-PCR was significant compared with
      those at E18, PN0 and PN28 in TRPC1 and TRPV4 channels, whereas an increase was
      observed but not significant in the others. On immunohistochemical staining at
      PN5, whereas strong reactions of anti-TRPM8 antibody, anti-TRPV3 and anti-TRPV4
      antibodies were observed in cells which proliferated from a terminal portion of
      cells arranged tubular structure which previously constituted mostly the
      submandibular gland. CONCLUSION: It was clarified that TRP channels are expressed
      in the rat submandibular gland in early developmental stage although cells
      constituting the submandibular gland are different from those in adult animals,
      suggesting that these TRP channels are involved in cell differentiation in at PN5
      into the adult submandibular gland during early development.

PMID- 27875792
TI  - Investigation of CD40 gene rs4810485 and rs1883832 mutations in patients with
      recurrent aphthous stomatitis.
AB  - OBJECTIVES: Recurrent aphthous stomatitis (RAS) is a common painful disorder
      affecting oral health, mucosa and overall quality of life. The etiopathogenesis
      of RAS remains unclear. RAS shows a large genetic diversity among the patients.
      In present study, we investigated whether CD40 gene rs4810485 and rs1883832 are
      associated with RAS and its clinical findings in Turkish patients. MATERIALS AND
      METHODS: Genomic DNA obtained from 387 individuals (160 patients with RAS and 227
      healthy controls) were used in the study. CD40 gene rs4810485 and rs1883832
      mutations were determined by using polymerase chain reaction with the specific
      primers. RESULTS: There was no statistically significant difference between the
      groups with respect to genotype and allele distribution (p>0.05, OR 0.94, 95% CI
      0.70-1.28, OR 1.01 95% CI 0.75-1.37, respectively). Additionally, there was no
      statistically significant difference in the combined genotype analysis of CD40
      gene rs4810485 and rs1883832 mutations (p>0.05). CONCLUSIONS: According to our
      results, we found that CD40 gene mutations are not associated with RAS. We are
      convinced that CD40 gene mutations do not predispose to develop RAS in Turkish
      population. To our knowledge, this is the first study regarding CD40 gene
      rs4810485 and rs1883832 mutations investigated in RAS patients.

PMID- 27875793
TI  - Detection and quantification of Aggregatibacter actinomycetemcomitans,
      Porphyromonas gingivalis and Streptococcus oralis in blood samples with different
      microbiological identification methods: An in vitro study.
AB  - BACKGROUND: Culture-based methods (culture broth bottles or lysis methods) have
      been the standard for detecting bacteremia. More recently, quantitative
      polymerase chain reaction (qPCR) was proposed as a more sensitive and specific
      test although none of them has been validated for the identification of
      periodontal pathogens (fastidious growing bacteria) in blood samples. OBJECTIVE:
      To compare the ability to detect and quantify Aggregatibacter
      actinomycetemcomitans, Porphyromonas gingivalis and Streptococcus oralis (alone
      or in combination) in blood samples with three culture techniques [direct
      anaerobic culturing (DAC), haemo-culture (BACTEC), and lysis-centrifugation (LC)]
      and a non-culture dependent approach (qPCR) in an in vitro study. MATERIAL AND
      METHODS: Blood samples from 12 periodontally healthy volunteers were contaminated
      with three concentrations [104,102 and 101 colony forming units (CFU)/mL] of A.
      actinomycetemcomitans, P. gingivalis and S. oralis, alone or in combination.
      Samples were analysed by DAC, BACTEC, LC and qPCR. Sensitivity, specificity,
      predictive values, kappa index and Lins correlation coefficients were calculated.
      RESULTS: DAC, LC and qPCR were able to detect the three target species at all
      concentrations. An excellent concordance (correlation coefficient r: 0.92-1) was
      observed between DAC and the reference standard (sensitivity raging 93.33-100%
      and specificity 88.89-100%) values. BACTEC was not able to identify P. gingivalis
      in any of the performed experiments. qPCR provided false negative results for
      S.oralis. CONCLUSIONS: DAC showed the best results for the proper identification
      and quantification of A. actinomycetemcomitans, P. gingivalis and S. oralis,
      alone or in combination, in blood samples.

PMID- 27875794
TI  - G protein signaling in plants: minus times minus equals plus.
AB  - Heterotrimeric G proteins are key regulators in the transduction of extracellular
      signals both in animals and plants. In plants, heterotrimeric G protein signaling
      plays essential roles in development and in response to biotic and abiotic
      stress. However, over the last decade it has become clear that plants have unique
      mechanisms of G protein signaling. Although plants share most of the core
      components of heterotrimeric G proteins, some of them exhibit unusual properties
      compared to their animal counterparts. In addition, plants do not share
      functional GPCRs. Therefore the well-established paradigm of the animal G protein
      signaling cycle is not applicable in plants. In this review, we summarize recent
      insights into these unique mechanisms of G protein signaling in plants with
      special focus on the evident potential of G protein signaling as a target to
      modify developmental and physiological parameters important for yield increase.

PMID- 27875795
TI  - Cerebellar hemisphere herniation in the neck: Case report of a very rare
      complication following a posterior fossa craniectomy.
AB  - This article presents a very rare late complication of surgery to the posterior
      fossa involving a craniectomy: cerebellar hemisphere herniation in the neck,
      through the craniectomy site. Here we also analyse the possible causes of such
      complication.

PMID- 27875796
TI  - Development of extensive inferior vena cava thrombosis due to the ligation of a
      large mesenteric-caval shunt during liver transplantation: A case report.
AB  - INSTRUCTION: Inferior vena cava (IVC) thrombosis can be a life-threatening
      complication after liver transplantation (LT). Although this complication is
      usually related to technical problems associated with vascular anastomosis, we
      report a case of IVC thrombosis which developed from a ligated large mesenteric
      caval shunt. PRESENTATION OF CASE: A 35-year-old man underwent LT from a brain
      dead donor for primary sclerosing cholangitis. Enhanced computed tomography (CT)
      before LT showed a huge collateral vessel of the inferior mesenteric vein (IMV)
      draining into the infra-renal IVC directly. To obtain sufficient portal vein (PV)
      flow, the dilated IMV collateral was ligated. A routine Doppler ultrasound study
      on post-operative day 1 showed thrombus inside the infra-hepatic IVC. Enhanced CT
      showed that this thrombus originated from a ligated collateral vessel of the IMV
      and extended into the IVC. He was hemodynamically stable and liver function was
      consistently stable. The size of IVC thrombus slowly reduced and he is currently
      in good condition without any symptoms. DISCUSSION: To obtain adequate PV flow,
      ligation of a major PSS at the time of LT has been suggested. However, where it
      should be occluded has not been discussed. We should occlude a mesenteric-caval
      shunt not only at the upper side, but at the IVC side, based on findings from the
      current case. CONCLUSION: To obtain appropriate PV flow toward a liver graft,
      occlusion of portosystemic shunts during LT is recommended. However, the position
      of ligation should be carefully considered to avoid extension of thrombus to
      major vessels.

PMID- 27875798
TI  - Parsimony and goodness-of-fit in multi-dimensional NMR inversion.
AB  - Multi-dimensional nuclear magnetic resonance (NMR) experiments are often used for
      study of molecular structure and dynamics of matter in core analysis and
      reservoir evaluation. Industrial applications of multi-dimensional NMR involve a
      high-dimensional measurement dataset with complicated correlation structure and
      require rapid and stable inversion algorithms from the time domain to the
      relaxation rate and/or diffusion domains. In practice, applying existing inverse
      algorithms with a large number of parameter values leads to an infinite number of
      solutions with a reasonable fit to the NMR data. The interpretation of such
      variability of multiple solutions and selection of the most appropriate solution
      could be a very complex problem. In most cases the characteristics of materials
      have sparse signatures, and investigators would like to distinguish the most
      significant relaxation and diffusion values of the materials. To produce an easy
      to interpret and unique NMR distribution with the finite number of the principal
      parameter values, we introduce a new method for NMR inversion. The method is
      constructed based on the trade-off between the conventional goodness-of-fit
      approach to multivariate data and the principle of parsimony guaranteeing
      inversion with the least number of parameter values. We suggest performing the
      inversion of NMR data using the forward stepwise regression selection algorithm.
      To account for the trade-off between goodness-of-fit and parsimony, the objective
      function is selected based on Akaike Information Criterion (AIC). The performance
      of the developed multi-dimensional NMR inversion method and its comparison with
      conventional methods are illustrated using real data for samples with bitumen,
      water and clay.

PMID- 27875799
TI  - Genetic modification technology for nutrition and improving diets: an ethical
      perspective.
AB  - Genetically modified (GM) techniques to improve the nutrition and health content
      of foods is a highly debated area riddled with ethical dilemmas. Assessing GM
      technology with a public health ethical framework, this paper identifies public
      health goals, the potential burdens of the technology, and areas to consider for
      minimizing burdens and ensuring beneficence, autonomy, and little infringements
      on justice. Both policymakers and food producers should acknowledge local food
      environments and the agricultural context of each community in order to
      effectively prepare communication strategies and equitably distribute any
      proposed GM food intervention.

PMID- 27875797
TI  - Determining lower threshold concentrations for synergistic effects.
AB  - Though only occurring rarely, synergistic interactions between chemicals in
      mixtures have long been a point of focus. Most studies analyzing synergistic
      interactions used unrealistically high chemical concentrations. The aim of the
      present study is to determine the threshold concentration below which proven
      synergists cease to act as synergists towards the aquatic crustacean Daphnia
      magna. To do this, we compared several approaches and test-setups to evaluate
      which approach gives the most conservative estimate for the lower threshold for
      synergy for three known azole synergists. We focus on synergistic interactions
      between the pyrethroid insecticide, alpha-cypermethrin, and one of the three
      azole fungicides prochloraz, propiconazole or epoxiconazole measured on Daphnia
      magna immobilization. Three different experimental setups were applied: A
      standard 48h acute toxicity test, an adapted 48h test using passive dosing for
      constant chemical exposure concentrations, and a 14-day test. Synergy was defined
      as occuring in mixtures where either EC50 values decreased more than two-fold
      below what was predicted by concentration addition (horizontal assessment) or as
      mixtures where the fraction of immobile organisms increased more than two-fold
      above what was predicted by independent action (vertical assessment). All three
      tests confirmed the hypothesis of the existence of a lower azole threshold
      concentration below which no synergistic interaction was observed. The lower
      threshold concentration, however, decreased with increasing test duration from
      0.026+/-0.013MUM (9.794+/-4.897MUgL-1), 0.425+/-0.089MUM (145.435+/-30.46MUgL-1)
      and 0.757+/-0.253MUM (249.659+/-83.44MUgL-1) for prochloraz, propiconazole and
      epoxiconazole in standard 48h toxicity tests to 0.015+/-0.004MUM (5.651+/
      1.507MUgL-1), 0.145+/-0.025MUM (49.619+/-8.555MUgL-1) and 0.122+/-0.0417MUM
      (40.236+/-13.75MUgL-1), respectively, in the 14-days tests. Testing synergy in
      relation to concentration addition provided the most conservative values. The
      threshold values for the vertical assessments in tests where the two could be
      compared were in general 1.2 to 4.7 fold higher than the horizontal assessments.
      Using passive dosing rather than dilution series or spiking did not lower the
      threshold significantly. Below the threshold for synergy, slight antagony could
      often be observed. This is most likely due to induction of enzymes active in
      metabolization of alpha-cypermethrin. The results emphasize the importance of
      test duration when assessing synergy, but also show that azole concentrations
      within the typically monitored range of up to 0.5MUgL-1 are not likely to cause
      severe synergy concerning Daphnia magna immobilization.

PMID- 27875800
TI  - Evaluation of TSPO PET imaging, a marker of glial activation, to study the
      neuroimmune footprints of morphine exposure and withdrawal.
AB  - INTRODUCTION: A growing area of research suggests that neuroimmunity may impact
      the pharmacology of opioids. Microglia is a key component of the brain immunity.
      Preclinical and clinical studies have demonstrated that microglial modulators may
      improve morphine-induced analgesia and prevent the development of tolerance and
      dependence. Positron emission tomography (PET) using translocator protein 18kDa
      (TSPO) radioligand is a clinically validated strategy for the non-invasive
      detection of microglial activation. We hypothesized that TSPO PET imaging may be
      used to study the neuroimmune component of opioid tolerance and withdrawal.
      METHODS: Healthy rats (n=6 in each group) received either saline or escalating
      doses of morphine (10-40mg/kg) on five days to achieve tolerance and a withdrawal
      syndrome after morphine discontinuation. MicroPET imaging with [18F]DPA-714 was
      performed 60h after morphine withdrawal. Kinetic modeling was performed to
      estimate [18F]DPA-714 volume of distribution (VT) in several brain regions using
      dynamic PET images and corresponding metabolite-corrected input functions.
      Immunohistochemistry (IHC) experiments on striatal brain slices were performed to
      assess the expression of glial markers (Iba1, GFAP and CD68) during 14days after
      morphine discontinuation. RESULTS: The baseline binding of [18F]DPA-714 to the
      brain (VT=0.086+/-0.009mLcm-3) was not increased by morphine exposure and
      withdrawal (VT=0.079+/-0.010mLcm-3) indicating the absence of TSPO
      overexpression, even at the regional level. Accordingly, expression of glial
      markers did not increase after morphine discontinuation. CONCLUSIONS: Morphine
      tolerance and withdrawal did not detectably activate microglia and had no impact
      on [18F]DPA-714 brain kinetics in vivo.

PMID- 27875802
TI  - Urgency traits moderate daily relations between affect and drinking to
      intoxication among young adults.
AB  - BACKGROUND: Young adults with higher trait urgency (i.e., a tendency to act
      rashly in response to heightened affect) may be especially vulnerable to heavy
      drinking. The current study examined 1) the influence of urgency on daily
      relations between affect and drinking to intoxication, and 2) whether urgency
      influenced the effectiveness of naltrexone (vs. placebo) for reducing alcohol
      use. METHODS: This study is a secondary analysis of data from 126 (n=40 female)
      heavy drinking young adults, ages 18-25, enrolled in a double-blind, 8-week
      clinical trial comparing brief motivational intervention and either naltrexone or
      placebo. Multilevel models examined whether trait urgency moderated daily
      relations between positive and negative affect and drinking to intoxication,
      measured by an estimated blood-alcohol concentration (eBAC) at or above the legal
      limit (>=0.08g%). Person-level interactions examined whether naltrexone was more
      effective than placebo at reducing the odds of eBAC>=0.08g% for individuals with
      higher vs. lower trait urgency. RESULTS: On days of greater within-person
      positive or negative affect, young adults with higher urgency were more likely to
      drink to intoxication than those with lower urgency. Naltrexone reduced the odds
      of drinking to intoxication significantly more than placebo, independent of
      positive or negative urgency. CONCLUSIONS: Although naltrexone treatment reduced
      drinking overall, young adults with higher trait urgency were still at increased
      risk for hazardous drinking following times of strong positive or negative mood.
      Targeted interventions are needed to reduce the risk of heavy drinking among
      young adults with high trait urgency.

PMID- 27875801
TI  - The widening gender gap in marijuana use prevalence in the U.S. during a period
      of economic change, 2002-2014.
AB  - AIM: Concurrently with increasingly permissive attitudes towards marijuana use
      and its legalization, the prevalence of marijuana use has increased in recent
      years in the U.S. Substance use is generally more prevalent in men than women,
      although for alcohol, the gender gap is narrowing. However, information is
      lacking on whether time trends in marijuana use differ by gender, or whether
      socioeconomic status in the context of the Great Recession may affect these
      changes. METHODS: Using repeated cross-sectional data from the National Survey on
      Drug Use and Health (2002-2014), we examined changes over time in prevalence of
      past-year marijuana use by gender, and whether gender differences varied across
      income levels. After empirically determining a change point in use in 2007, we
      used logistic regression to test interaction terms including time, gender, and
      income level. RESULTS: Prevalence of marijuana use increased for both men (+4.0%)
      and women (+2.7%) from 2002 to 2014, with all of the increase occurring from 2007
      to 2014. Increases were greater for men, leading to a widening of the gender gap
      over time (p<0.001). This divergence occurred primarily due to increased
      prevalence among men in the lowest income level (+6.2%) from 2007 to 2014.
      CONCLUSION: Our findings are consistent with other studies documenting increased
      substance use during times of economic insecurity, especially among men.
      Corresponding with the Great Recession and lower employment rate beginning in
      2007, low-income men showed the greatest increases in marijuana use during this
      period, leading to a widening of the gender gap in prevalence of marijuana use
      over time.

PMID- 27875803
TI  - Analysis of alcohol use disorders from the Nathan Kline Institute-Rockland
      Sample: Correlation of brain cortical thickness with neuroticism.
AB  - BACKGROUND: Although differences in both neuroanatomical measures and personality
      traits, in particular neuroticism, have been associated with alcohol use
      disorders (AUD), whether lifetime AUD diagnosis alters the relationship between
      neuroticism and neuroanatomical structures remains to be determined. METHODS:
      Data from 65 patients with lifetime AUD diagnoses and 65 healthy comparisons (HC)
      group-matched on age, sex and race were extracted from the Nathan Kline Institute
      - Rockland Sample data set. Each subject completed personality trait measures and
      underwent MRI scanning. Cortical thickness measures at 68 Desikan-Killiany Atlas
      regions were obtained using FreeSurfer 5.3.0. Regression analyses were performed
      to identify brain regions at which the neuroticism-cortical thickness
      relationship was altered by lifetime AUD status. RESULTS: As expected, AUDs had
      higher neuroticism scores than HCs. Correlations between neuroticism and cortical
      thickness in the left insula and right fusiform differed significantly across
      groups. Higher neuroticism score in AUD and the interaction between the insular
      cortical thickness-neuroticism correlation and AUD status were confirmed in a
      replication study using the Human Connectome Project data set. CONCLUSIONS:
      Results confirmed the relationship between neuroticism and AUD and suggests that
      specific cortical regions, particularly the left insula, represent anatomic
      substrates underlying this association in AUD.

PMID- 27875805
TI  - Voluntary aerobic exercise increases arterial resilience and mitochondrial health
      with aging in mice.
AB  - Mitochondrial dysregulation and associated excessive reactive oxygen species
      (mtROS) production is a key source of oxidative stress in aging arteries that
      reduces baseline function and may influence resilience (ability to withstand
      stress). We hypothesized that voluntary aerobic exercise would increase arterial
      resilience in old mice. An acute mitochondrial stressor (rotenone) caused greater
      (further) impairment in peak carotid EDD in old (~27 mo., OC, n=12; -32.5+/-
      10.5%) versus young (~7 mo., YC n=11; -5.4+/-- 3.7%) control male mice, whereas
      arteries from young and old exercising (YVR n=10 and OVR n=11, 10-wk voluntary
      running; -0.8+/--2.1% and -8.0+/-4.9%, respectively) mice were protected. Ex-vivo
      simulated Western diet (WD, high glucose and palmitate) caused greater impairment
      in EDD in OC (-28.5+/-8.6%) versus YC (-16.9+/-5.2%) and YVR (-15.3+/-2.3%),
      whereas OVR (-8.9+/-3.9%) were more resilient (not different versus YC).
      Simultaneous ex-vivo treatment with mitochondria-specific antioxidant MitoQ
      attenuated WD-induced impairments in YC and OC, but not YVR or OVR, suggesting
      that exercise improved resilience to mtROS-mediated stress. Exercise normalized
      age-related alterations in aortic mitochondrial protein markers PGC-1alpha, SIRT
      3 and Fis1 and augmented cellular antioxidant and stress response proteins. Our
      results indicate that arterial aging is accompanied by reduced resilience and
      mitochondrial health, which are restored by voluntary aerobic exercise.

PMID- 27875804
TI  - Optogenetic approaches for dissecting neuromodulation and GPCR signaling in
      neural circuits.
AB  - Optogenetics has revolutionized neuroscience by providing means to control cell
      signaling with spatiotemporal control in discrete cell types. In this review, we
      summarize four major classes of optical tools to manipulate neuromodulatory GPCR
      signaling: opsins (including engineered chimeric receptors); photoactivatable
      proteins; photopharmacology through caging-photoswitchable molecules; fluorescent
      protein based reporters and biosensors. Additionally, we highlight technologies
      to utilize these tools in vitro and in vivo, including Cre dependent viral vector
      expression and two-photon microscopy. These emerging techniques targeting
      specific members of the GPCR signaling pathway offer an expansive base for
      investigating GPCR signaling in behavior and disease states, in addition to
      paving a path to potential therapeutic developments.

PMID- 27875807
TI  - On the heterogeneity of human populations as reflected by mortality dynamics.
AB  - The heterogeneity of populations is used to explain the variability of mortality
      rates across the lifespan and their deviations from an exponential growth at
      young and very old ages. A mathematical model that combines the heterogeneity
      with the assumption that the mortality of each constituent subpopulation
      increases exponentially with age, has been shown to successfully reproduce the
      entire mortality pattern across the lifespan and its evolution over time. In this
      work we aim to show that the heterogeneity is not only a convenient consideration
      for fitting mortality data but is indeed the actual structure of the population
      as reflected by the mortality dynamics over age and time. In particular, we show
      that the model of heterogeneous population fits mortality data better than other
      commonly used mortality models. This was demonstrated using cohort data taken for
      the entire lifespan as well as for only old ages. Also, we show that the model
      can reproduce seemingly contradicting observations in late-life mortality
      dynamics. Finally, we show that the homogenisation of a population, observed by
      fitting the model to actual data of consecutive periods, can be associated with
      the evolution of allele frequencies if the heterogeneity is assumed to reflect
      the genetic variations within the population.

PMID- 27875808
TI  - Increased Soluble Suppression of Tumorigenicity 2 Level Predicts All-Cause and
      Cardiovascular Mortality in Maintenance Hemodialysis Patients: A Prospective
      Cohort Study.
AB  - BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) is a novel
      cardiovascular biomarker. This study aimed to evaluate the prognostic value of
      sST2 in hemodialysis patients. METHODS: Four hundred and fourteen maintenance
      hemodialysis (MHD) patients were enrolled and followed up prospectively. Serum
      sST2 levels were measured. The endpoint was all-cause and cardiovascular
      mortality. RESULTS: During a median follow-up of 22.3 months, 58 patients died,
      including 31 cardiovascular deaths. sST2 was an independent predictor of all
      cause mortality with a relative risk (RR) of 1.31 (95% CI 1.000-1.717, p = 0.050)
      and cardiovascular mortality with an RR of 2.10 (95% CI 1.507-2.927, p < 0.001).
      The prognostic value of sST2 was additive to N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT), as the
      combined use of sST2 and NT-proBNP or hs-cTnT better identified higher-risk
      patients. CONCLUSION: Elevated sST2 is an independent predictor of all-cause and
      cardiovascular mortality in MHD patients. A combined use of sST2 and NT-proBNP or
      hs-cTnT helps identify individuals of higher risk.

PMID- 27875809
TI  - Impact of Pseudomonas aeruginosa Infection on Respiratory Muscle Function in
      Adult Cystic Fibrosis Patients.
AB  - BACKGROUND: Pseudomonas aeruginosa infection impairs respiratory muscle function
      in adolescents with cystic fibrosis, but its impact on adult patients has not
      been characterised. OBJECTIVES: To investigate respiratory muscle function in
      adult cystic fibrosis patients according to P. aeruginosa status (repetitive
      samples over 12 months). METHODS: The pressure-time index of the respiratory
      muscles (PTImus), a measure of their efficiency, served as the primary outcome.
      In addition, respiratory load and maximal respiratory muscle strength were
      assessed. RESULTS: In 51 patients examined (65% female; median age 32 years, IQR
      24-40), a median of 3.0 (IQR 2-4) different pathogens was found in each patient.
      The PTImus was 0.113 and 0.126 in Pseudomonas-positive (n = 33) and -negative (n
      = 18) patients, respectively (p = 0.53). Univariate analysis showed a lower
      PTImus in male than in female patients (p = 0.006). Respiratory muscle load and
      strength were otherwise comparable, with the exception of higher nasal sniff
      pressures in Pseudomonas-positive patients who were chronically infected (>50% of
      positive samples). Quality of Life (according to the Cystic Fibrosis
      Questionnaire-Revised) was higher if both respiratory load and the PTImus were
      low (high respiratory muscle efficiency). CONCLUSIONS: Chronic P. aeruginosa
      infection does not influence respiratory muscle efficiency in adult cystic
      fibrosis patients with otherwise multiple co-infections. In addition, patients
      with reduced respiratory muscle efficiency had worse Quality of Life.

PMID- 27875811
TI  - Prospective Case-Control Study of Abnormal Bleeding after Outpatient
      Corticosteroid Injection.
AB  - OBJECTIVE: This study is aimed at evaluating the incidence of bleeding among
      women having outpatient corticosteroid injection compared to matched controls,
      using mailed surveys and electronic health records. STUDY DESIGN: Prospective
      survey study of women receiving outpatient corticosteroid injection for joint or
      back pain (cases) compared to women matched for visit, diagnosis of joint/back
      pain, and age, who did not receive an injection (controls). A survey was mailed
      45 days following outpatient visit, inquiring about menstrual history, abnormal
      bleeding, and potential risk factors. The proportion of women reporting abnormal
      bleeding was compared between cases and controls, and stratified by menopausal
      status. RESULTS: One thousand and sixty two surveys were mailed to 531 identified
      cases/control pairs, and 40% response was seen from each group. Of 379 analyzable
      responders, 135 (36%) were premenopausal and 244 (64%) postmenopausal.
      Postmenopausal women who had a corticosteroid injection were more likely to
      report recent abnormal bleeding compared to controls (17 vs. 7%, p = 0.02),
      whereas rates were similar among premenopausal women (50 vs. 43%, p = 0.39). When
      logistic regression was performed, injection was associated with bleeding among
      postmenopausal women, independent of body mass index and hormone use.
      CONCLUSIONS: Corticosteroid injection is associated with increased abnormal
      vaginal bleeding among postmenopausal women.

PMID- 27875812
TI  - Hemodialysis Decreases the Etiologically-Related Early Vascular Aging Observed in
      End-Stage Renal Disease: A 5-Year Follow-Up Study.
AB  - AIMS: To analyze the early vascular aging (EVA) in end-stage renal disease (ESRD)
      patients, attempting to determine a potential association between EVA and the
      etiology of ESRD, and to investigate the association of hemodialysis and EVA in
      ESRD patients during a 5-year follow-up period. METHODS: Carotid-femoral pulse
      wave velocity (cfPWV) was obtained in 151 chronically hemodialyzed patients (CHP)
      and 283 control subjects, and in 25 CHP, who were followed-up after a 5-year
      lapse. RESULTS: cfPWV increased in ESRD patients compared to control subjects.
      The cfPWV-age relationship was found to have a steeper increase in ESRD patients.
      The highest cfPWV and EVA values were observed in patients with diabetic
      nephropathy. Regression analysis demonstrated a significant reduction of the EVA
      in HD patients on a 5-year follow-up. CONCLUSION: Patients in ESRD showed higher
      levels of EVA. cfPWV and EVA differed in ESRD patients depending on their renal
      failure etiology. CHP showed an EVA reduction after a 5-year follow-up period.

PMID- 27875810
TI  - Nonstructural Protein 1 of Tick-Borne Encephalitis Virus Induces Oxidative Stress
      and Activates Antioxidant Defense by the Nrf2/ARE Pathway.
AB  - BACKGROUND: Infection with tick-borne encephalitis virus (TBEV) causes
      pathological changes in the central nervous system. However, the possible redox
      alterations in the infected cells that can contribute to the virus pathogenicity
      remain unknown. OBJECTIVE: In the current study we explored the ability of TBEV
      nonstructural protein 1 (NS1) to induce oxidative stress and activate antioxidant
      defense via the nuclear factor (erythroid-derived-2)-like 2/antioxidant response
      element (Nrf2/ARE) pathway. METHODS: HEK 293T cells were transfected with plasmid
      encoding NS1 protein, and the production of reactive oxygen species (ROS) was
      measured using oxidation-sensitive dyes, the activation of the ARE promoter was
      estimated using a reporter plasmid, and the expression of phase II detoxifying
      enzymes was quantified by measuring their mRNA levels using RT-qPCR. RESULTS: A
      high level of ROS production was detected in cells transfected with NS1
      expressing plasmid. In addition, this protein activated the promoter with an ARE
      and upregulated the transcription of ARE-dependent genes that encode phase II
      enzymes. CONCLUSION: TBEV NS1 protein both triggers ROS production and activates
      a defense Nrf2/ARE pathway. These data suggest that a role of redox-mediated
      processes in TBEV-induced damage of the central nervous system should also be
      explored. These data can contribute to a better understanding of TBEV
      pathogenicity, further improvement of TBE treatment, and the development of
      vaccine candidates against this infection.

PMID- 27875813
TI  - Memories of a Professor Emeritus.

PMID- 27875806
TI  - Mast cells and histamine are triggering the NF-kappaB-mediated reactions of adult
      and aged perilymphatic mesenteric tissues to acute inflammation.
AB  - This study aimed to establish mechanistic links between the aging-associated
      changes in the functional status of mast cells and the altered responses of
      mesenteric tissue and mesenteric lymphatic vessels (MLVs) to acute inflammation.
      We used an in vivo model of acute peritoneal inflammation induced by
      lipopolysaccharide treatment of adult (9-month) and aged (24-month) F-344 rats.
      We analyzed contractility of isolated MLVs, mast cell activation, activation of
      nuclear factor-kappaB (NF-kappaB) without and with stabilization of mast cells by
      cromolyn or blockade of all types of histamine receptors and production of 27
      major pro-inflammatory cytokines in adult and aged perilymphatic mesenteric
      tissues and blood. We found that the reactivity of aged contracting lymphatic
      vessels to LPS-induced acute inflammation was abolished and that activated mast
      cells trigger NF-kappaB signaling in the mesentery through release of histamine.
      The aging-associated basal activation of mesenteric mast cells limits acute
      inflammatory NF-kappaB activation in aged mesentery. We conclude that proper
      functioning of the mast cell/histamine/NF-kappaB axis is necessary for reactions
      of the lymphatic vessels to acute inflammatory stimuli as well as for interaction
      and trafficking of immune cells near and within the collecting lymphatics.

PMID- 27875814
TI  - Characterisation of Prognosis and Invasion of Cutaneous Squamous Cell Carcinoma
      by Podoplanin and E-Cadherin Expression.
AB  - BACKGROUND: Around 5% of all cutaneous squamous cell carcinoma (cSCC)
      metastasise. Metastases usually locate in regional skin and lymph nodes,
      suggesting collective cancer invasion. The cellular level of tumour invasion and
      prognostic parameters remain to be characterised. METHODS: We performed
      immunohistochemical analyses of E-cadherin (marker for collective cancer
      invasion) and podoplanin (marker for epithelial-mesenchymal transition [EMT],
      single-cell invasion) expression in 102 samples of metastatic and non-metastatic
      cSCC and 18 corresponding skin and lymph node metastases to characterise the
      invasion of cSCC. Immunohistochemical results were retrospectively correlated
      with clinical data. RESULTS: E-cadherin was highly expressed in metastatic and
      non-metastatic cSCC and skin metastases. This suggests collective cancer
      invasion. However, E-cadherin was downregulated in poorly differentiated cSCC and
      lymph node metastases, suggesting partial EMT. Podoplanin was significantly
      upregulated in metastatic (p = 0.002) and poorly differentiated (p = 0.003) cSCC.
      Overexpression of podoplanin represented a statistically independent prognostic
      factor for disease-free survival (p = 0.014). CONCLUSION: Collective cancer
      invasion is likely in cSCC. In lymph node metastases and poorly differentiated
      cSCC, partial EMT is possible. Podoplanin is an independent prognostic parameter
      for metastasis.

PMID- 27875815
TI  - Wang's Forceps-Assisted Catheter Reposition and Fixation: An Easy and Reliable
      Rescue Method.
AB  - Catheter migration and omental wrap are the most common causes of catheter
      malfunction, which usually result in catheter removal or replacement. The
      conventional open surgery for catheter reposition has many disadvantages. A new
      tunnel is needed throughout the procedure of catheter replacement causing more
      pain and frustration to the patients. Another drawback is that the incidence of
      catheter migration after conventional catheter reposition surgery is still as
      high as it was before the procedure. Wang's forceps, an instrument commonly used
      in our peritoneal dialysis center, is easy and effective in catheter insertion
      and fixation. Recently, we have successfully used the Wang's forceps to resolve
      the catheter displacement for 10 patients, including 1 patient who suffered from
      catheter tip migration 3 times and had undergone conventional catheter rescue by
      both open surgery and laparoscopy. This new technique was easy and reliable, and
      the original tunnel was maintained, which reduced pain and risk of infection in
      the patients. These advantages may grant the Wang's forceps technique favorable
      over the conventional surgical approach.

PMID- 27875816
TI  - Serum Magnesium and Mortality in Maintenance Hemodialysis Patients.
AB  - BACKGROUND AND AIM: The study aimed to investigate the potential contributing
      effect of serum magnesium on mortality in maintenance hemodialysis (MHD)
      patients. METHODS: The patients receiving regular MHD in March 2013 were
      involved. Baseline data including clinical data, anthropometrics and biochemical
      measurement were collected. After being followed for 36 months, the time of death
      and reason were recorded. RESULTS: One hundred and thirty-five MHD patients were
      enrolled in the study and analyzed, with mean serum magnesium of 1.11 +/- 0.15
      mmol/l. The level of serum magnesium in 64 patients was normal (47.4%), and it
      was elevated in 71 of the 135 patients (52.6%). And none of MHD patients had
      hypomagnesemia. The levels of serum albumin (Alb), urea nitrogen, creatinine
      (Cr), uric acid and phosphorus were significantly higher, but high-sensitivity C
      reactive protein (Hs-CRP) and lipoprotein A were significantly lower in
      hypermagnesemia group compared to the normal serum magnesium group (p < 0.05).
      Serum Alb, serum Cr, serum phosphorus and Hs-CRP were related factors of
      hypermagnesemia by multivariate logistic regression analysis (p < 0.05). During
      the 36 months of follow-up, 27 patients died (20.0%), of whom 55.6% died of
      cardiovascular (CV) events. Kaplan-Meier curves showed that cumulative incidence
      of CV mortality were significantly higher in the normal serum magnesium group
      than in the hypermagnesemia group (p = 0.027); however, there was no significant
      difference in all-cause mortality (p > 0.05). CONCLUSIONS: Serum magnesium was
      elevated, which was related with nutrition and inflammation markers including
      serum Alb, serum Cr, serum phosphorus and Hs-CRP. Lower serum magnesium is a risk
      factor of CV mortality in MHD patients. Intervention studies are needed to
      clarify whether magnesium supplementation is beneficial for improving patient
      prognosis, when MHD patients had inflammatory and malnutrition.

PMID- 27875817
TI  - Association of Preoperative Platelet-to-Lymphocyte Ratio with Atrial Fibrillation
      after Coronary Artery Bypass Graft Surgery.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      platelet-to-lymphocyte ratio (PLR) and atrial fibrillation (AF) after coronary
      artery bypass graft (CABG) surgery. SUBJECTS AND METHODS: A total of 125 patients
      were retrospectively analyzed. AF was diagnosed using standard clinical criteria,
      and PLR was calculated as the ratio of the platelets to lymphocytes, obtained
      from the blood samples that were taken in the fasting state before CABG surgery.
      The association of different variables with postoperative AF and PLR was
      calculated using univariate and multivariate analysis. The receiver operating
      characteristics curve was used to determine the sensitivity and specificity of
      PLR and the optimal cutoff value for predicting post-CABG AF. RESULTS: Of the 125
      patients, 50 with AF (mean age: 67.0 +/- 9.5 years, 38 males and 12 females) and
      75 patients without AF (mean age: 61.1 +/- 9.1 years, 58 males and 17 females)
      were identified, and the difference in the mean age was statistically significant
      (p = 0.01). PLR was also significantly higher in those with AF (152.8 +/- 82.2)
      than those without AF (118.2 +/- 32.9) (p = 0.012). Univariate analysis showed
      that age and PLR were associated with AF after CABG surgery (p < 0.001 and p =
      0.005, respectively). Using a multivariate logistic regression model with the
      backward elimination method, age and PLR remained as independent predictors of AF
      after CABG surgery (p < 0.001 and p = 0.005, respectively). PLR levels >119.3
      predicted postoperative AF with 64% sensitivity and 56% specificity (AUC: 0.634,
      p = 0.012). CONCLUSION: In this study, age and PLR level were independent
      predictors of AF after CABG surgery. Patients with an elevated preoperative PLR
      were at higher risk of AF after CABG surgery.

PMID- 27875818
TI  - The Expression of CCAT2, a Novel Long Noncoding RNA Transcript, and rs6983267
      Single-Nucleotide Polymorphism Genotypes in Colorectal Cancers.
AB  - Colon cancer-associated transcription 2 (CCAT2) was recently identified as a
      novel long noncoding RNA transcript encompassing the single-nucleotide
      polymorphism rs6983267. CCAT2 is overexpressed in colorectal cancer (CRC) where
      it promotes tumor growth, metastasis, and chromosomal instability, although the
      clinical relevance of this enhanced expression is unknown. In this retrospective
      study, CCAT2 expression was evaluated using real-time polymerase chain reaction
      in 149 CRC patients, and its associations with clinicopathological
      characteristics, outcome, rs6983267 genotypes, microsatellite status, DNA ploidy,
      and BubR1 expression were analyzed. CCAT2 expression in cancer tissue was
      significantly higher than in noncancer tissue (p < 0.001), particularly in cases
      of metastatic cancer (p < 0.001). However, relative CCAT2 expression levels and
      rs6983267 genotypes were not correlated with clinicopathological features or
      patient prognosis. CRC cases demonstrating high CCAT2 expression were all
      microsatellite stable (p < 0.005). Together, this indicates that CCAT2 expression
      was associated with microsatellite-stable CRC.

PMID- 27875819
TI  - New Zealand Applied Neurosciences Conference. Auckland, New Zealand, November 24
      26, 2016: Abstracts.

PMID- 27875820
TI  - Local and Global HIV Aging Demographics and Research.
AB  - This introduction serves to foreground current patterns associated with HIV and
      aging, globally. We highlight key trends by World Health Organization sub-region,
      and identify gaps in existing knowledge. HIV and aging is insufficiently
      documented, as prevalence data for those over age 49 have not generally been
      captured by many countries, or by UNAIDS. Despite limited data and data systems,
      several dominant trends among adults aged 50 and older are discernible,
      including: growing HIV risk and prevalence is increasingly evident among maturing
      adults, worldwide; older individuals at risk of or living with HIV, and their
      health providers, fail to recognize risk and symptoms, leading to disease
      progression and delayed treatment. Cross-sectoral strategies will be needed to
      mount responses; public health campaigns will be essential in educating and
      informing individuals about HIV risk, prevention and care; and special efforts to
      tailor interventions to key populations most vulnerable or stigmatized in
      countries will be critical.

PMID- 27875821
TI  - Are HIV-Infected Older Adults Aging Differently?
AB  - With increasing success in treating HIV, infected persons are living longer, and
      a new challenge has emerged - the need to understand how HIV-infected adults are
      aging. What are the similarities with typical aging and what are the unique
      aspects that may have resulted from HIV infection, interacting with
      characteristic life style factors and other comorbid conditions? Are specific
      diseases and conditions (comorbidities), typically seen as part of the aging
      process, occurring at accelerated rates or with higher frequency (accentuated) in
      HIV-infected adults? At this juncture, conclusions should be tentative.
      Certainly, biological processes that correlate with aging occur earlier in the
      older adult HIV population. Clinical manifestations of these biological processes
      are age-associated illnesses occurring in greater numbers (multimorbidity), but
      they are not accelerated. Specifically cardiovascular disease, certain cancers,
      and renal disease are more common with other comorbidities less certain.
      Management of this elevated risk for developing multimorbidity is a major concern
      for patients and their health care teams. The medical system must respond to the
      evolving needs of this aging and growing older adult population who will dominate
      the epidemic. Adopting a more holistic approach to their health care management
      is needed to achieve optimal health and well-being in the HIV-infected older
      adult. Geriatric care principles best embody this approach.

PMID- 27875822
TI  - Cellular Senescence, Immunosenescence and HIV.
AB  - Aging is a complex biological process that leads to several physiological
      changes. Among these changes, the most striking are those involving the innate
      and adaptive parts of the immune system. Furthermore, these changes are
      associated with a low-grade inflammation called inflamm-aging, which is the
      result of several lifelong antigenic stimulations, including chronic viral
      infections such as cytomegalovirus. Immunosenescence, concomitantly with inflamm
      aging, is considered as the leading cause of age-related diseases including
      cardiovascular, neurodegenerative and metabolic diseases, and cancer. HIV
      infection, once considered a unique deadly infectious disease, has now become a
      chronic disease with efficacious highly active antiretroviral therapy. This
      signifies that the treatment transforms HIV infection from a chronic infection to
      a chronic inflammatory disease. Most people with HIV infection become aged, and
      older adults have been contracting HIV infection. Thus, there is a great interest
      to study HIV infection in relation to immunosenescence and inflamm-aging to
      determine whether immunosenescence contributes to HIV infection, or if HIV is
      causing immunosenescence and, as such, represents a premature immunosenescence
      and accelerated aging. Although there are many similarities in the immune and
      inflammatory changes and the occurrence of age-related chronic diseases between
      normal aging and HIV infection, the interaction between these processes is not
      well understood, and consequently the concept that HIV infection is an
      accelerated aging model is questioned. Future studies are needed to effectively
      answer this question for the better care of HIV-infected elderly patients.

PMID- 27875823
TI  - Biomarkers and Clinical Indices of Aging with HIV.
AB  - HIV infection may potentiate specific biomarkers that influence the development
      of premature clinical indices commonly associated with aging. Therefore,
      predicting mortality outcomes in people living with HIV is extremely important as
      this population ages. This chapter describes biomarkers associated with
      inflammation, coagulation, and immune activation in HIV, and reviews the
      association between specific biomarkers and the development of co-morbid
      conditions in individuals with HIV. Measures that incorporate specific biomarkers
      related to HIV infection, designed to predict mortality outcomes in individuals
      with HIV, are also discussed.

PMID- 27875824
TI  - Multimorbidity and Burden of Disease.
AB  - With effective antiretroviral therapy, HIV has become a chronic disease, and life
      expectancy among HIV-infected persons is approaching that of HIV-uninfected
      persons. Despite this success, epidemiologic evidence suggests that the burden of
      multiple aging-related diseases, including cardiovascular disease, liver disease,
      metabolic abnormalities, chronic kidney disease, cognitive dysfunction, and
      osteoporosis, is higher in HIV-infected persons compared to their HIV-uninfected
      peers. These comorbid diseases tend to cluster in a single person, leading to
      multimorbidity and polypharmacy. Emerging evidence suggests that multimorbidity
      among HIV-infected persons results in functional decline, reduced quality of
      life, and increased mortality. In this review, we examine the epidemiology, risk
      factors, etiologies, and potential consequences of multimorbidity in aging HIV
      infected persons. With aggressive risk factor management for comorbidities and
      less toxic antiretroviral medications, the burden of multimorbidity in HIV
      infected persons can be reduced.

PMID- 27875825
TI  - Polypharmacy, Using New Treatments to Customize Care for Aging Patients and
      Adherence Present and Future.
AB  - Nearly 50% of HIV patients in the US are now over 50, and the problem of
      comorbidities associated with the aging process is becoming increasingly
      complicated. In this chapter, we will review the challenge of polypharmacy and
      suggest ways of minimizing drug-drug interactions. Newer medications and
      combinations that reduce the pill burden, and allow the healthcare provider to
      customize HIV treatment while remaining mindful of other medical issues will be
      addressed. Adherence to medication schedules and possible future alternative drug
      delivery systems will also be presented.

PMID- 27875826
TI  - Behavioral Health.
AB  - In this chapter, we will describe the state of the literature on behavioral
      health, which includes mental health and substance use problems, and the
      available treatment interventions to ameliorate these problems, for older adults
      living with HIV (OALH). The scientific literature on the behavioral health of
      OALH is highly underdeveloped, especially in terms of the creation of empirically
      supported interventions to alleviate psychological distress. From the literature
      that does exist, there are a number of salient factors that emerge, including
      stereotypes (i.e., older adults are not sexually active), stigmatization (of
      those who are HIV-positive), social isolation, unique psychosocial needs for
      newly-infected OALH, and elevated rates of emotional distress and concomitant
      disorders - especially, depression. These factors persist alongside findings that
      OALH have fewer sources of social or institutional support, fewer surviving
      peers, and a lack of family to care for them. Additionally, many OALH report
      problems with substance use, both as a function of their 'baby-boomer'
      generational status (i.e., people born between 1946 and 1964) and in terms of the
      life experiences associated with their HIV-positive status. Overall, it is
      unclear how mental health and substance use problems affect combination
      antiretroviral therapy adherence, multimorbidity, polypharmacy, or treatment
      outcomes in this population, and further study is needed.

PMID- 27875827
TI  - Disability among Persons Aging with HIV/AIDS.
AB  - Persons surviving to older ages with HIV/AIDS often face an accelerated aging
      accompanied by increased comorbidity and decline in health and function. In this
      chapter, we review the process of disablement among persons aging with HIV/AIDS,
      from chronic conditions to impairments and functional limitations, leading to
      disability. Chronic immune activation related to chronic HIV infection may
      contribute to early development of chronic conditions that are common in older
      adults resulting in premature disablement. Anatomical and physiological changes
      related to the aging process make people vulnerable to physical and cognitive
      impairments. In old age, quality of life depends mainly on avoidance and
      management of age-associated diseases rather than chronological parameters.
      Interventions to manage chronic conditions associated with aging may have a
      significant impact on quality of life in older persons with HIV infection.
      Because of the complexity of physical and cognitive impairments among persons
      aging with HIV infection, a range of supports and interventions will be needed to
      effectively address the problem of disablement in this population.

PMID- 27875829
TI  - Sexual Health, Risk and Prevention.
AB  - Sexuality is an important aspect of health across the lifespan and includes sex,
      gender identities, sexual orientation, intimacy, pleasure, reproduction, and free
      from coercion and discrimination. In 2010, individuals 50 years and older living
      with HIV in the US made up 8.5 per 100,000 persons affected by the virus, with
      African Americans accounting for 46% of seroconversion in the same year, which
      was 10.7 times greater than Whites. African American women are particularly at
      risk. Although there are many promising HIV prevention interventions to date,
      there are few that focus specifically on older adults. This chapter raises
      methodological concerns in research that focuses on sexual health of older adults
      living with HIV infection and special concerns regarding the older adult
      population's sexual health risk and suggested clinical interventions.

PMID- 27875828
TI  - Application of Geriatric Principles and Care Models in HIV and Aging.
AB  - People aging with HIV present a unique challenge for providers. HIV-infected
      patients experience accentuated aging and multimorbidity, but are typically
      disconnected from geriatric care, which is limited by a shortage of geriatric
      providers worldwide. Consequently, HIV providers are tasked with managing
      multiple age-related illnesses, within service networks that are historically not
      designed to care for aging patients. While comfortable with the management of
      antiretroviral therapy, HIV providers may have limited training on how to
      recognize or manage geriatric syndromes, especially in the context of
      multimorbidity. The result is an emerging, vulnerable population, and the
      question is how to best care for them. As part of the answer, we offer examples
      of how providers can use geriatric principles to improve the care of aging HIV
      infected patients. We begin by describing basic geriatric concepts and examples
      of care models, and subsequently use a patient case to illustrate their
      applications at the patient level. At the system level, we discuss how HIV
      service networks can use components of geriatric care models to meet the needs of
      aging HIV-infected patients. Lastly, we identify aging-specific guidelines and
      service integration as important areas for future endeavors.

PMID- 27875830
TI  - Stigma in an Aging Context.
AB  - Both the Joint United Nations Program on HIV/AIDS and the US National HIV/AIDS
      Strategy identify HIV stigma as a barrier to care, a barrier to service access,
      and deleterious to personal and social well-being. This chapter discusses the
      topic of HIV stigma from a conceptual basis, including the mechanisms of
      prejudice and discrimination, and defining anticipated, enacted, and internalized
      stigma. Stigma is then placed in a historical context of HIV and AIDS, and events
      exacerbating HIV stigma are discussed. The components of HIV stigma are then
      applied to the population of older adults (age 50 years and older) who are at
      risk of or living with HIV infection. The importance of intersectionality is
      discussed with regard to race, ethnicity, gender, sexual orientation, gender
      identity, and in particular, age. Drawing upon the HIV and gerontological
      literature, the chapter outlines characteristics found to be protective against
      stigma and placing older adults at greater risk for HIV stigma. Stigma management
      strategies are outlined and finally, implications of working with older adults
      related to HIV stigma are provided.

PMID- 27875831
TI  - Social Support Systems and Social Network Characteristics of Older Adults with
      HIV.
AB  - Social networks of older adults with HIV have been characterized as fragile, with
      a greater reliance on friends as compared to family. However, we know little
      about the subgroup differences in the social network constellations of this
      population, how such characteristics are related to social support resources, and
      their relationship with psychosocial well-being. We developed a typology of
      social networks of older HIV-positive adults and examined if they would be
      related to receipt of informal assistance, perceptions of support sufficiency,
      and psychosocial well-being. Data were obtained from Research on Older Adults
      with HIV (n = 914). Participants were 50 years and older, HIV positive, and
      diverse in terms of race/ethnicity, gender, and sexual orientation. Cluster
      analysis identified Isolated, Friend-centered, and Integrated social network
      types. The Isolated reported significantly lower levels of assistance, lower
      perceptions of support availability and adequacy, greater stigma and
      psychological distress, and lower well-being compared to their peers. While
      friends dominate many social networks in this population, a more nuanced
      interpretation is needed; many have no friends and a substantial proportion
      receive significant family support. Those with Isolated network types will likely
      need to access a high volume of community-based services as they age as they lack
      informal support resources.

PMID- 27875832
TI  - Remediating HIV-Associated Neurocognitive Disorders via Cognitive Training: A
      Perspective on Neurocognitive Aging.
AB  - Over 50% of adults with HIV exhibit some form of HIV-associated neurocognitive
      disorder, ranging from mild asymptomatic neurocognitive impairment to HIV
      associated dementia. As adults age with HIV and become susceptible to
      cardiovascular and metabolic comorbidities, the prevalence and severity of such
      neurocognitive disorders are likely to increase. With compromised renal and
      hepatic functioning often accompanying HIV, pharmaceutical interventions to
      address such neurocognitive disorders may not be the best strategy and are not
      without risks. Fortunately, as noted in the geriatric literature, cognitive
      training strategies have been shown to improve targeted neurocognitive domains
      and everyday functioning. A review of some of these cognitive training
      strategies, especially as they relate to aging with HIV, are highlighted and
      explained in the context of neuroAIDS, aging, and neurocognitive reserve.
      Implications for practice and research are provided.

PMID- 27875833
TI  - Mental Health, Psychosocial Challenges and Resilience in Older Adults Living with
      HIV.
AB  - In addition to physical health challenges, older people living with HIV/AIDS
      (PLWHA) experience mental health burdens and challenges to their social well
      being that diminish their overall health. These health states are synergistic and
      are driven by HIV and HIV treatments, the aging process itself, and psychosocial
      and structural conditions of their lives. However, resilience, which we
      understand as both a trait and a process, may serve to buffer the effects that
      HIV/HIV treatments, aging, and social/structural conditions may have on the
      overall well-being of the individual. In this chapter, we examine the extant
      literate on the mental health and psychosocial challenges experienced by older
      PLWHA as elements of the total health of the individual. We also provide a
      contextualization and conceptualization for understanding the significant role
      that resilience may play in empowering individuals to enact processes which
      buffer health from the stressors. In this perspective, the health of older PLWHA
      must be viewed through a lens of power and strength rather than one of deficit.
      We conclude by outlining a theoretical paradigm for the role of resilience in the
      health of older HIV-positive adults, which may serve as a guide to clinicians,
      public health practitioners, and researchers working with this population.

PMID- 27875834
TI  - Medical, Social and Supportive Services for Older Adults with HIV.
AB  - Older people living with HIV are increasingly requiring formal supportive
      community-based services. Supportive services are essential to medical care and
      treatment for older people living with HIV/AIDS. This chapter considers
      Andersen's behavioral model of health services, and explores the predisposing,
      enabling, and need factors that affect service utilization among the older HIV
      population. The Andersen model provides a lens to understand the need for
      supportive services to go beyond primary medical care. Examples of such services
      and referrals typically include medical and non-medical case management, clinical
      provider referrals, mental health and substance use treatment, housing
      assistance, legal services, nutrition, transportation, home care, emergency
      assistance, patient education support groups, and other programs such as the AIDS
      Drug Assistance Program and secondary prevention services. Barriers to assistance
      and support, and consequences and resources for caregivers are addressed. Aspects
      surrounding structural inequities, multiple-minority status, and HIV stigma are
      examined with the goal of offering insight and advocacy ideas for community-based
      providers and policy makers. In future, the healthcare and supportive services
      infrastructure must be better equipped to manage the distinctive treatment and
      care needs of HIV-positive older adults.

PMID- 27875835
TI  - The Relevance of Palliative Care in HIV and Aging.
AB  - The connection between palliative care and HIV infection has deep and wide roots
      in the United States that go back to the time when many gay men in the early
      1980s were dying from a disease we knew little about, and there was no way to
      help but to alleviate symptoms in hospice and end of life centers across the
      United States. More individuals (adults and children), families, and communities
      attribute the success of antiretroviral therapies and other therapeutic
      approaches to advancing quality of life and life itself today. The identity of
      HIV, like many 'life-threatening illness with no cure' has evolved as a 'chronic'
      condition with a longer time period to address physical, social, and emotional
      experiences that may concern those living with HIV infection. Chronic conditions
      create an opportunity for healthcare providers from all types of disciplines to
      rethink and retool their knowledge and skills, to have conversations with those
      affected by HIV infection as to what they would ideally want in addressing their
      care needs; care needs that are now complicated by comorbid conditions of aging
      and healthcare reimbursement that uniquely intersect with HIV infection. This
      chapter addresses the current relevance of palliative care in HIV history, both
      nationally and internationally, and offers ideas for health professionals to use
      a multidisciplinary integration of knowledge to not just cure but align 'cure and
      care' toward healing action while being present to others from their perspective
      and values.

PMID- 27875837
TI  - Erratum.

PMID- 27875836
TI  - Ageism, Aging and HIV: Community Responses to Prevention, Treatment, Care and
      Support.
AB  - Ageism, in the form of prejudice, stereotyping, and discrimination targeting
      older adults, represents a barrier to addressing the graying of the HIV epidemic.
      There is widespread misperception on the part of older adults themselves, as well
      as service providers and society in general that HIV risk is low as one ages. In
      addition, internalized ageism may play a role in poorer physical and mental
      health outcomes, as the negative stereotypes associated with aging become a self
      fulfilling prophecy. A number of steps can be taken to address HIV and aging in
      the context of ageism with regard to: prevention, education, and outreach;
      treatment guidelines for older adults with HIV; funding to address the aging of
      the epidemic; engagement of communities, health and social service organizations,
      and other providers around mental health and social support, and addressing the
      needs of special populations. Caring for an aging population with HIV represents
      a challenge, which is exacerbated in low and/or middle-income countries that
      typically lack the infrastructure of high resource settings. How we address the
      aging-related issues of the HIV epidemic across regions and settings could serve
      as a model in dealing with aging in our society in general regardless of HIV
      status.

PMID- 27875838
TI  - Contents Vol. 81, 2016.

PMID- 27875839
TI  - Severe Metabolic Acidosis and Hepatopathy due to Leukoencephalopathy with
      Thalamus and Brainstem Involvement and High Lactate.
AB  - Leukoencephalopathy with thalamus and brainstem involvement and high lactate
      (LTBL) is a recently described autosomal recessive mitochondrial disease
      characterized by early onset of neurological symptoms, a biphasic clinical
      course, and distinctive neuroimaging. Pathogenic variants in the EARS2 gene that
      encode for mitochondrial glutamyl-tRNA synthetase are responsible for LTBL. Here,
      we describe the clinical course of an infant diagnosed with an acute crisis of
      LTBL and severe liver disease. This article illustrates the utility of blood
      lactate quantification in addition to basic metabolic testing and brain imaging
      in a child with low tone and poor growth. In addition, this case demonstrates the
      utility of current genetic diagnostic testing, in lieu of more invasive
      procedures, in obtaining rapid answers in this very complicated group of
      disorders.

PMID- 27875840
TI  - Application of a diathermic dilator for negotiating near-total antropyloric
      strictures.

PMID- 27875841
TI  - Endoscopic submucosal dissection of pancreatic heterotopia in children.

PMID- 27875842
TI  - Through-the-mesh technique after endoscopic ultrasonography-guided
      hepaticogastrostomy: a novel re-intervention method.

PMID- 27875843
TI  - Underwater endoscopic mucosal resection without submucosal lift.

PMID- 27875844
TI  - Fracture of a self-expanding metal stent used to manage a post-vertical sleeve
      gastrectomy stenosis.

PMID- 27875845
TI  - Colonoscopic extraction of a chicken wishbone stuck in the sigmoid colon,
      identified as diverticulitis: the patient's and doctor's wish comes true.

PMID- 27875846
TI  - Endoscopic full-thickness resection of a submucosal right colon lesion.

PMID- 27875847
TI  - Duodenal arteriovenous malformation: endosonographic diagnosis and coil
      embolization.

PMID- 27875848
TI  - Multimodal therapy of recurrent and refractory bleeding from esophageal varices -
      case report and review of the literature.
AB  - Bleeding from esophageal varices is a major cause of mortality in patients with
      advanced liver disease. Although standard treatment and secondary prophylaxis are
      effective, in some patients sustained hemostasis cannot be achieved. We report
      the case of a woman with alcoholic liver disease in whom pharmacological,
      endoscopic, and intravascular therapies failed to control variceal bleeding. Only
      a combination of (repeated) band ligation, insertion of a self-expanding metal
      stent, TIPS implantation and redilatation, transjugular variceal embolization,
      and finally implantation of a portocaval shunt proved to be successful. We
      discuss the stepwise approach to this situation and the challenges encountered in
      the process.

PMID- 27875849
TI  - [Short- and long-term results in operable pancreatic ductal adenocarcinomas from
      a cooperation between two departments gastroenterology-visceral surgery at non
      university hospitals benchmarked to results of expert-centers].
AB  - The only curative approach in pancreatic ductal adenocarcinoma (PDAC) is
      resection, which is possible only in 15 - 30 % of patients. Local tumor spread or
      distant metastases are contraindications for resection in the majority of
      patients. Surgical-oncological quality with short- and long-term results are
      varying tremendously, so that "expertise/quality" are associated to hospital- or
      surgeon's volume and/or center formation. The treatment results also depend, to a
      great extent, on the medical diagnostic quality. With our retrospective study, we
      aim to compare the results-quality of cooperative pancreatic cancer treatment
      based on an extensive preoperative diagnostic procedure for staging and risk
      estimation in a specialized GI-medical department and visceral surgical
      oncological expertise in pancreatic cancer surgery at a general hospital with the
      results-quality of expert centers. Fifty-three patients with PDAC had diagnosis
      and resection of their cancer between 1/2002 and 12/2009. The 30 day hospital
      mortality was 3.8 % and the median survival time after demission from the
      hospital was 23.1 months. The 5-year-survival rate of R0-resected patients, all
      of whom had received adjuvant chemotherapy, was high with 31 %. The survival data
      and the extraordinarily high resection rate of 98.1 % in the patient group, whose
      primary tumor stage was pT3 in 81 %, reflects the excellent cooperation of high
      standards in medical diagnostic processes, visceral pancreatic surgery, and
      adjuvant medical chemotherapy. The results are well comparable to those of "high
      volume centers". The responsible heads of the two departments have been trained
      at university expert centers. Expertise in the treatment of pancreatic cancer
      patients may be successfully transferred from an expert center to a general
      hospital, if the team has high expertise.

PMID- 27875851
TI  - Comment On: Peripartum Cardiomyopathy Treatment with Dopamine Agonist and
      Subsequent Pregnancy with a Satisfactory Outcome.

PMID- 27875850
TI  - ?

PMID- 27875852
TI  - Computerized Cardiotocography Analysis: Comparison among Several Parental Ethnic
      Origins.
AB  - Objective We speculate that genetic racial disparity exists in fetal life and can
      be detected by modern computerized cardiotocography (cCTG). Methods This is a
      retrospective study comparing the results of the cCTG of pregnant patients at 37
      42 weeks according to the parental ethnicity (black versus white). A cCTG was
      performed to analyze the variables of fetal heart rate (FHR). The cCTG variables
      analyzed were: percentage of signal loss; number of contractions; basal FHR;
      number of accelerations; number of decelerations; length of high variation
      episodes; short-term variability (STV); total trace duration time; and number of
      fetal active movements. Non-stress test (NST) parameters in the two groups were
      compared using the Mann-Whitney test for continuous data, and the Chi-square test
      for categorical variables. Results We found a significantly lower number of
      active fetal movements (p = 0.007) and longer periods of low variation (p =
      0.047) in the cCTG of black patients when compared with white patients.
      Conclusions In conclusion, identifying the factors responsible for the variance
      in the objective analysis of CTG results is important to improve the outcomes of
      patients. Our study lends further evidence as to the importance of ethnicity in
      clinical cCTG interpretation.

PMID- 27875853
TI  - Use of endoscopic septotomy for the treatment of late staple-line leaks after
      laparoscopic sleeve gastrectomy.
AB  - Background Staple-line leak following laparoscopic sleeve gastrectomy is a dire
      adverse event. While the treatment of acute and early leaks is well established,
      there is still dispute regarding late and chronic leaks. We describe an
      endoscopic approach combining septotomy and sleeve stricture dilation for
      treating late/chronic leaks. Methods Ten consecutive patients with late/chronic
      proximal leaks were treated at our center. The septum separating the sleeve lumen
      from the perigastric cavity was progressively dissected over several sessions and
      the downstream stricture was pneumatically dilated. The technical and clinical
      success rates were evaluated. Results: All ten patients were treated
      successfully. Eight patients had sleeve strictures that were dilated in
      conjunction with septotomy. A mean of five sessions over the course of 43 days
      was needed to complete treatment. In two patients with a small perigastric cavity
      and no stricture, septotomy was achieved with through-the-scope balloon dilation
      of the fistula. No adverse events were encountered. Conclusions Septotomy
      accompanied by stricture dilation seems highly effective and safe in late and
      chronic leaks following sleeve gastrectomy.

PMID- 27875854
TI  - Duodenal endoscopic submucosal dissection is feasible using the pocket-creation
      method.
AB  - Background and study aims Duodenal endoscopic submucosal dissection (ESD)
      requires sophisticated endoscopic techniques because of a high rate of
      perforation. We introduced the pocket-creation method (PCM) of duodenal ESD to
      overcome difficulties. The aim of this study was to evaluate the safety and
      usefulness of ESD using the PCM for superficial tumors of the duodenum. Patients
      and methods We performed ESD of 17 non-ampullary duodenal lesions using the
      conventional method and of 28 lesions using the PCM from 2006 to 2015 and
      retrospectively reviewed the results, comparing the PCM and the conventional
      method. The median follow-up period was 35 months (range 2 - 97). Results There
      were more lesions at the duodenal angles in the PCM group compared with the
      conventional method group (54 % [15/28] vs. 22 % [4/17]; P = 0.048), and the
      resected specimen diameter was larger in the PCM than the conventional method
      group (median 37 mm [range 25 - 101] vs. 25 mm [15 - 55]; P = 0.007). Dissection
      speed was faster in the PCM than the conventional method group (9.4 mm2/min [3.0 
      15.7] vs. 6.5 mm2/min [1.5 - 19.7]; P = 0.09). En bloc resection was more
      frequent in the PCM (100 % [28/28]) than the conventional method group (88 %
      [15/17]) (P = 0.07). Perforation was significantly less frequent in the PCM (7 %
      [2/28]) than the conventional method group (29 % [5/17]; P = 0.046). The one
      delayed perforation in the conventional method group required surgical repair,
      while other intraprocedural perforations were treated by clipping. There were no
      recurrences. Conclusions ESD of duodenal lesions can be safely performed using
      the PCM, which stabilizes the tip of the endoscope even in difficult locations.

PMID- 27875856
TI  - Antimicrobial resistance surveillance in the genomic age.
AB  - The loss of effective antimicrobials is reducing our ability to protect the
      global population from infectious disease. However, the field of antibiotic drug
      discovery and the public health monitoring of antimicrobial resistance (AMR) is
      beginning to exploit the power of genome and metagenome sequencing. The creation
      of novel AMR bioinformatics tools and databases and their continued development
      will advance our understanding of the molecular mechanisms and threat severity of
      antibiotic resistance, while simultaneously improving our ability to accurately
      predict and screen for antibiotic resistance genes within environmental,
      agricultural, and clinical settings. To do so, efforts must be focused toward
      exploiting the advancements of genome sequencing and information technology.
      Currently, AMR bioinformatics software and databases reflect different scopes and
      functions, each with its own strengths and weaknesses. A review of the available
      tools reveals common approaches and reference data but also reveals gaps in our
      curated data, models, algorithms, and data-sharing tools that must be addressed
      to conquer the limitations and areas of unmet need within the AMR research field
      before DNA sequencing can be fully exploited for AMR surveillance and improved
      clinical outcomes.

PMID- 27875855
TI  - Endoscopic ultrasound-guided gallbladder drainage reduces adverse events compared
      with percutaneous cholecystostomy in patients who are unfit for cholecystectomy.
AB  - Background and study aim There are no data comparing endoscopic ultrasound (EUS)
      guided gallbladder drainage (EGBD) with percutaneous cholecystostomy as a
      treatment for patients with acute cholecystitis. Patients and methods This was a
      1 : 1 matched cohort study of all patients who were unfit for cholecystectomy and
      underwent EGBD or percutaneous cholecystostomy instead for the treatment of acute
      cholecystitis. The outcomes were matched for age, sex, and American Society of
      Anesthesiologists grade. Outcome measures included the technical and clinical
      success rates, adverse events, hospital stay, the number of unplanned admissions,
      and mortality. Results Between November 2011 and August 2014, a total of 118
      patients were included in the study (59 EGBD, 59 percutaneous cholecystostomy).
      Technical and clinical success rates were similar. In the EGBD group,
      significantly fewer patients suffered from overall adverse events (19 [32.2 %]
      vs. 44 [74.6 %]; P < 0.001) and serious adverse events (14 [23.7 %] vs. 44 [74.6
      %]; P < 0.001) compared to the percutaneous cholecystostomy group. Patients in
      the EGBD group required fewer unplanned admissions (4 [6.8 %] vs. 42 [71.2 %]; P
      < 0.001), which were due to problems related to the cholecystostomy tube in 95.2
      %. The 30-day adverse event rates were similar between the groups (17 [28.8 %]
      vs. 10 [16.9 %]; P = 0.13). For instance, recurrent acute cholecystitis occurred
      in 0 patients in the EGBD group and in 4 (6.8 %) patients in the percutaneous
      cholecystostomy group (P = 0.12). The 30-day mortality rates were non
      significantly higher in the EGBD group (5 [8.5 %] vs. 1 [1.7 %]; P = 0.21).
      Conclusions EGBD and percutaneous cholecystostomy were both effective means of
      achieving gallbladder drainage. EGBD may be a promising alternative to
      percutaneous cholecystostomy for treatment of acute cholecystitis in patients who
      are unfit for surgery, provided that experienced endosonographers are available.

PMID- 27875857
TI  - Retrospective review of Prothrombinex use by SAAS MedSTAR.
AB  - OBJECTIVE: The aim of this study was to review and describe the use of
      Prothrombinex by a physician-led retrieval service based remote from a hospital
      blood bank. METHODS: This is a retrospective observational study. Patients to
      whom Prothrombinex was administered by the retrieval team were identified from
      the retrieval service patient database. The paper case cards of the identified
      patients were then manually reviewed and the data matched to patients in the
      state-wide electronic laboratory record. RESULTS: Between 1 January 2010 and 30
      November 2013 38 cases were identified. For 28 the indication was warfarinisation
      associated with life-threatening bleeding (most commonly intracranial or
      gastrointestinal tract). In the remaining 10 cases, Prothrombinex was used to
      treat coagulopathy associated with liver disease or massive haemorrhage. The
      median time saved by the retrieval team administering PTX-VF, rather than waiting
      to the receiving centre, was 120 min (interquartile range: 85-195 min). The
      median dose of PTX-VF administered was 23.25 IU/kg (interquartile range: 20-33
      IU/kg). Paired international normalised ratios (INRs) were available for 33 of
      the 38 patients. In the warfarin group, all patients had an improvement in their
      INR and 21 of 25 had correction of their INR. In the non-warfarin group, the
      effect on INR was more variable. CONCLUSION: Prothrombinex is a clinically useful
      product that can be relatively easily stored and used by retrieval services, even
      if they are based in isolation from a hospital blood bank. More research is
      required to look at the utility of Prothrombinex for non-warfarin-related
      bleeding in the pre-hospital and retrieval environment.

PMID- 27875858
TI  - Contemporary rates of pathological features and mortality for adenocarcinoma of
      the urinary bladder in the USA.
AB  - OBJECTIVES: To examine contemporary rates of pathological features and mortality
      for adenocarcinoma of the urinary bladder in the USA using population-based data
      analysis. METHODS: We relied on 10 024 patients with non-metastatic bladder
      cancer diagnosed between 2004 and 2013 within the Surveillance, Epidemiology and
      End Results registries. Logistic regression analyses focused on grade and stage.
      Kaplan-Meier analyses assessed cancer-specific mortality rates in adenocarcinoma
      and urothelial carcinoma of the bladder. Cox regression analyses assessed the
      impact of histological subtype on cancer-specific mortality. RESULTS: Overall,
      215 (2.1%) adenocarcinoma and 9809 (97.9%) urothelial carcinoma patients were
      identified. The rate of non-organ-confined disease was higher in adenocarcinoma
      (64.7% vs 50.8%, P < 0.001). In multivariable logistic regression analyses,
      adenocarcinoma patients had a 2.2-fold higher risk of harboring non-organ
      confined disease (95% confidence interval 1.7-3.0; P < 0.001) than urothelial
      carcinoma patients. Cancer-specific mortality-free survival rates were lower in
      adenocarcinoma (P < 0.01). This disadvantage only applied to non-organ-confined
      disease (P = 0.044), and not to organ-confined disease (P = 0.9). In
      multivariable Cox regression analyses, adenocarcinoma conferred a 1.3-fold higher
      rate of cancer-specific mortality (hazard ratio 1.30, 95% confidence interval
      1.05-1.60; P = 0.01). Among adenocarcinoma patients, 30.7% harbored signet-ring
      cell adenocarcinoma and portended particularly poor cancer-specific mortality
      rates. CONCLUSIONS: In bladder cancer, adenocarcinoma presents at higher stages
      than urothelial carcinoma. However, cancer-specific mortality rates do not
      differ. A more unfavorable stage at diagnosis and higher cancer-specific
      mortality apply to the signet-ring cell variant.

PMID- 27875859
TI  - Clinical significance of preoperative renal function and gross hematuria for
      intravesical recurrence after radical nephroureterectomy for upper tract
      urothelial carcinoma.
AB  - OBJECTIVES: To investigate the predictive values of perioperative factors and to
      develop a nomogram for intravesical recurrence after radical nephroureterectomy
      in patients with upper urinary tract urothelial carcinoma. METHODS: A
      retrospective analysis of 144 patients who underwent radical nephroureterectomy
      from 1996 to 2014 was carried out. The actuarial probabilities of the
      intravesical recurrence-free survival rate were calculated using the Kaplan-Meier
      method. Prognostic indicators for intravesical recurrence were identified using
      competing-risks regression analyses. RESULTS: Intravesical recurrence occurred in
      63 patients during the follow-up period. The intravesical recurrence-free
      survival rates at 1, 3, and 5 years were 65.7%, 50.6% and 47.1%, respectively. In
      univariate analysis, the presence of gross hematuria (P = 0.028) and the
      preoperative serum creatinine level (P = 0.033) were significantly associated
      with intravesical recurrence. In multivariate analysis, the presence of gross
      hematuria (subdistribution hazard ratio 2.03, 95% CI 1.145-3.496; P = 0.013) and
      the preoperative serum creatinine level (subdistribution hazard ratio 3.15, 95%
      CI 1.161-3.534; P = 0.021) were independent predictors for intravesical
      recurrence after radical nephroureterectomy. Accordingly, a nomogram based on the
      model was developed. The concordance index of this model was 0.632. CONCLUSION:
      The presence of gross hematuria and preoperative serum creatinine levels seem to
      be independent predictors for intravesical recurrence after radical
      nephroureterectomy. Our nomogram developed based on these factors might aid in
      appropriate patient selection for clinical trials of novel therapeutic
      interventions, including administration of intravesical chemotherapy.

PMID- 27875860
TI  - The phase behavior study of human antibody solution using multi-scale modeling.
AB  - Phase transformation in antibody solutions is of growing interest in both
      academia and the pharmaceutical industry. Recent experimental studies have shown
      that, as in near-spherical proteins, antibodies can undergo a liquid-liquid phase
      separation under conditions metastable with respect to crystallization. However,
      the phase diagram of the Y-shaped antibodies exhibits unique features that differ
      substantially from those of spherical proteins. Specifically, antibody solutions
      have an exceptionally low critical volume fraction (CVF) and a broader and more
      asymmetric liquid-liquid coexistence curve than those of spherical proteins.
      Using molecular dynamics simulation on a series of trimetric Y-shaped coarse
      grained models, we investigate the phase behavior of antibody solutions and
      compare the results with the experimental phase diagram of human immunoglobulin G
      (IgG), one of the most common Y-shape typical of antibody molecules. With the
      fitted size of spheres, our simulation reproduces both the low CVF and the
      asymmetric shape of the experimental coexistence curve of IgG antibodies. The
      broadness of the coexistence curve can be attributed to the anisotropic nature of
      the inter-protein interaction. In addition, the repulsion between the inner parts
      of the spherical domains of IgG dramatically expands the coexistence region in
      the scaled phase diagram, while the hinge length has only a minor effect on the
      CVF and the overall shape of the coexistence curve. We thus propose a seven-site
      model with empirical parameters characterizing the exclusion volume and the hinge
      length of the IgG molecules, which provides a base for simulation studies of the
      phase behavior of IgG antibodies.

PMID- 27875861
TI  - Analyzing signal attenuation in PFG anomalous diffusion via a non-Gaussian phase
      distribution approximation approach by fractional derivatives.
AB  - Anomalous diffusion exists widely in polymer and biological systems. Pulsed-field
      gradient (PFG) techniques have been increasingly used to study anomalous
      diffusion in nuclear magnetic resonance and magnetic resonance imaging. However,
      the interpretation of PFG anomalous diffusion is complicated. Moreover, the exact
      signal attenuation expression including the finite gradient pulse width effect
      has not been obtained based on fractional derivatives for PFG anomalous
      diffusion. In this paper, a new method, a Mainardi-Luchko-Pagnini (MLP) phase
      distribution approximation, is proposed to describe PFG fractional diffusion. MLP
      phase distribution is a non-Gaussian phase distribution. From the fractional
      derivative model, both the probability density function (PDF) of a spin in real
      space and the PDF of the spin's accumulating phase shift in virtual phase space
      are MLP distributions. The MLP phase distribution leads to a Mittag-Leffler
      function based PFG signal attenuation, which differs significantly from the
      exponential attenuation for normal diffusion and from the stretched exponential
      attenuation for fractional diffusion based on the fractal derivative model. A
      complete signal attenuation expression Ealpha(-Dfbalpha,beta*) including the
      finite gradient pulse width effect was obtained and it can handle all three types
      of PFG fractional diffusions. The result was also extended in a straightforward
      way to give a signal attenuation expression of fractional diffusion in PFG
      intramolecular multiple quantum coherence experiments, which has an nbeta
      dependence upon the order of coherence which is different from the familiar n2
      dependence in normal diffusion. The results obtained in this study are in
      agreement with the results from the literature. The results in this paper provide
      a set of new, convenient approximation formalisms to interpret complex PFG
      fractional diffusion experiments.

PMID- 27875862
TI  - Communication: Probing the existence of partially arrested states in ionic
      liquids.
AB  - The recent predictions of the self-consistent generalized Langevin equation
      theory, describing the existence of unusual partially arrested states in the
      context of ionic liquids, were probed using all-atom molecular dynamics
      simulations of a room-temperature ionic liquid. We have found a slower diffusion
      of the smaller anions compared with the large cations for a wide range of
      temperatures. The arrest mechanism consists on the formation of a strongly
      repulsive glass by the anions, stabilized by the long range electrostatic
      potential. The diffusion of the less repulsive cations occurs through the holes
      left by the small particles. All of our observations in the simulated system
      coincide with the theoretical picture.

PMID- 27875863
TI  - A theory of diffusion controlled reactions in polyatomic molecule system.
AB  - The conventional Smoluchowski equation has been extensively utilized to
      investigate diffusion controlled reactions. However, application of the equation
      is limited to spherical-particle system. In the present study, a new Smoluchowski
      equation for polyatomic molecular system is derived based on Zwanzig-Mori
      projection operator method and reference interaction site model (RISM) theory.
      The theory is applied to monoatomic molecular liquid, and the obtained time
      dependent rate constant is virtually identical with that from conventional
      Smoluchowski equation. For diatomic molecular liquid, time-dependent distribution
      function and rate constant are obtained, showing a good agreement with those from
      molecular dynamics simulation.

PMID- 27875864
TI  - Vertical excitation energies from the adiabatic connection.
AB  - Vertical single-particle excitations from closed-shell ground states are
      complicated by the fact that the singlet open-shell states are, even in the first
      approximation, two-determinantal. Thus two-electron integrals come into play and
      standard time-independent DFT (density-functional theory) does not apply. In this
      work, we use the "adiabatic connection" to analyse the role of the two-electron
      integrals, obtaining a time-independent DFT approach to excitation-energy
      calculations that is new and simple. A non-empirical modeling of the method works
      as well as the popular TD-B3LYP time-dependent approach to excited states, and
      can be made even simpler by introducing one reasonable semi-empirical parameter.

PMID- 27875865
TI  - Molecular weight effects on interfacial properties of linear and ring polymer
      melts: A molecular dynamics study.
AB  - Using molecular dynamics simulations, we study and compare the pressure, P, and
      the surface tension, gamma, of linear chains and of ring polymers at the hard
      walls confining both melts into a slit. We examine the dependence of P and gamma
      on the length (i.e., molecular weight) N of the macromolecules. For linear
      chains, we find that both pressure and surface tension are inversely proportional
      to the chain length, P(N)-P(N->infinity)?N-1,gamma(N)-gamma(N->infinity)?N-1,
      irrespective of whether the confining planes attract or repel the monomers. In
      contrast, for melts comprised of cyclic (ring) polymers, neither the pressure nor
      the surface tension is found to depend on molecular weight N for both kinds of
      wall-monomer interactions. While other structural properties as, e.g., the
      probability distributions of trains and loops at impenetrable walls appear
      quantitatively indistinguishable, we observe an amazing dissimilarity in the
      probability to find a chain end or a tagged monomer of a ring at a given distance
      from the wall in both kinds of polymeric melts. In particular, we demonstrate
      that the conformational equivalence of linear chains in a confined melt to a
      single chain under conditions of critical adsorption to a planar surface,
      established two decades ago, does also hold for ring polymers in a melt of linear
      chains. This analogy does not hold, however, for linear and ring chains in a
      confined melt of ring chains.

PMID- 27875866
TI  - Salting-out effects by pressure-corrected 3D-RISM.
AB  - We demonstrate that using a pressure corrected three-dimensional reference
      interaction site model one can accurately predict salting-out (Setschenow's)
      constants for a wide range of organic compounds in aqueous solutions of NaCl. The
      approach, based on classical molecular force fields, offers an alternative to
      more heavily parametrized methods.

PMID- 27875867
TI  - Introducing new reactivity descriptors: "Bond reactivity indices." Comparison of
      the new definitions and atomic reactivity indices.
AB  - A new methodology to obtain reactivity indices has been defined. This is based on
      reactivity functions such as the Fukui function or the dual descriptor and makes
      it possible to project the information of reactivity functions over molecular
      orbitals instead of the atoms of the molecule (atomic reactivity indices). The
      methodology focuses on the molecule's natural bond orbitals (bond reactivity
      indices) because these orbitals (with physical meaning) have the advantage of
      being very localized, allowing the reaction site of an electrophile or
      nucleophile to be determined within a very precise molecular region. This
      methodology gives a reactivity index for every Natural Bond Orbital (NBO), and we
      have verified that they have equivalent information to the reactivity functions.
      A representative set of molecules has been used to test the new definitions.
      Also, the bond reactivity index has been related with the atomic reactivity one,
      and complementary information has been obtained from the comparison. Finally, a
      new atomic reactivity index has been defined and compared with previous
      definitions.

PMID- 27875869
TI  - Coarse-grained simulations for flow of complex soft matter fluids in the bulk and
      in the presence of solid interfaces.
AB  - We present a coarse-grained particle-based simulation technique for modeling flow
      of complex soft matter fluids such as polymer solutions in the presence of solid
      interfaces. In our coarse-grained description of the system, we track the motion
      of polymer molecules using their centers-of-mass as our coarse-grain co-ordinates
      and also keep track of another set of variables that describe the background flow
      field. The coarse-grain motion is thus influenced not only by the interactions
      based on appropriate potentials used to model the particular polymer system of
      interest and the random kicks associated with thermal fluctuations, but also by
      the motion of the background fluid. In order to couple the motion of the coarse
      grain co-ordinates with the background fluid motion, we use a Galilean invariant,
      first order Brownian dynamics algorithm developed by Padding and Briels [J. Chem.
      Phys. 141, 244108 (2014)], which on the one hand draws inspiration from smoothed
      particle hydrodynamics in a way that the motion of the background fluid is
      efficiently calculated based on a discretization of the Navier-Stokes equation at
      the positions of the coarse-grain coordinates where it is actually needed, but
      also differs from it because of the inclusion of thermal fluctuations by having
      momentum-conserving pairwise stochastic updates. In this paper, we make a few
      modifications to this algorithm and introduce a new parameter, viz., a friction
      coefficient associated with the background fluid, and analyze the relationship of
      the model parameters with the dynamic properties of the system. We also test this
      algorithm for flow in the presence of solid interfaces to show that appropriate
      boundary conditions can be imposed at solid-fluid interfaces by using artificial
      particles embedded in the solid walls which offer friction to the real fluid
      particles in the vicinity of the wall. We have tested our method using a model
      system of a star polymer solution at the overlap concentration.

PMID- 27875868
TI  - Optimized parameter selection reveals trends in Markov state models for protein
      folding.
AB  - As molecular dynamics simulations access increasingly longer time scales,
      complementary advances in the analysis of biomolecular time-series data are
      necessary. Markov state models offer a powerful framework for this analysis by
      describing a system's states and the transitions between them. A recently
      established variational theorem for Markov state models now enables modelers to
      systematically determine the best way to describe a system's dynamics. In the
      context of the variational theorem, we analyze ultra-long folding simulations for
      a canonical set of twelve proteins [K. Lindorff-Larsen et al., Science 334, 517
      (2011)] by creating and evaluating many types of Markov state models. We present
      a set of guidelines for constructing Markov state models of protein folding;
      namely, we recommend the use of cross-validation and a kinetically motivated
      dimensionality reduction step for improved descriptions of folding dynamics. We
      also warn that precise kinetics predictions rely on the features chosen to
      describe the system and pose the description of kinetic uncertainty across
      ensembles of models as an open issue.

PMID- 27875870
TI  - Communication: Cargo towing by artificial swimmers.
AB  - An active swimmer can tow a passive cargo by binding it to form a self-propelling
      dimer. The orientation of the cargo relative to the axis of the active dimer's
      head is determined by the hydrodynamic interactions associated with the
      propulsion mechanism of the latter. We show how the tower-cargo angular
      configuration greatly influences the dimer's diffusivity and, therefore, the
      efficiency of the active swimmer as a micro-towing motor.

PMID- 27875871
TI  - Remote detection of hyperpolarized 129Xe resonances via multiple distant dipolar
      field interactions with 1H.
AB  - A remote detection scheme utilizing the distant dipolar field interaction between
      two different spin species was proposed by Granwehr et al. [J. Magn. Reson.
      176(2), 125 (2005)]. In that sequence 1H spins were detected indirectly via their
      dipolar field interaction with 129Xe spins, which served as the sensing spins.
      Here we propose a modification of the proposed detection scheme that takes
      advantage of the longer T1 relaxation time of xenon to create a long lasting
      dipolar field with which the fast relaxing 1H spins are allowed to interact many
      times during a single acquisition. This new acquisition scheme improves detection
      sensitivity, but it also presents some challenges.

PMID- 27875872
TI  - Obtaining the solid-liquid interfacial free energy via multi-scheme thermodynamic
      integration: Ag-ethylene glycol interfaces.
AB  - The solid-liquid interfacial free energy gammasl is an important quantity in
      wetting, nucleation, and crystal growth. Although various methods have been
      developed to calculate gammasl with atomic-scale simulations, such calculations
      still remain challenging for multi-component interfaces between molecular fluids
      and solids. We present a multi-scheme thermodynamic integration method that is
      inspired by the "cleaving-wall" method and aimed at obtaining gammasl for such
      systems using open-source simulation packages. This method advances two aspects
      of its predecessor methods. First, we incorporate separate schemes to resolve
      difficulties when manipulating periodic boundary conditions of the supercell
      using open-source simulation packages. Second, we introduce a numerical
      approximation to obtain thermodynamic integrands for complex force fields when an
      analytical differentiation is not readily available. To demonstrate this method,
      we obtain gammasl for interfaces between Ag(100) and Ag(111) and ethylene glycol
      (EG). These interfacial free energies mirror interfacial potential energies for
      each facet. We also estimate entropies of interface formation and these are
      consistent with theoretical predictions in signs and trends. For the Ag-EG
      systems, we find that the largest contribution to gammasl is the free energy to
      create the bare metal surfaces. The second-largest contribution to gammasl is
      from the liquid-solid interaction. This user-friendly method will accelerate
      investigation in a broad range of research topics, such as the thermodynamic
      effect of structure-directing agents in solution-phase shape-controlled
      nanocrystal syntheses.

PMID- 27875873
TI  - Experimental study on the relationship between the frequency-dependent shear
      viscosity and the intermediate scattering function of representative viscous
      liquids.
AB  - The frequency-dependent shear viscosity of two representative viscous liquids, o
      terphenyl and glycerin, was experimentally determined at several temperatures and
      compared with the intermediate scattering functions reported in the literature. A
      comparison based on mode-coupling theory succeeded in relating the frequency
      dependent shear viscosity with the intermediate scattering function at the main
      peak of the static structure factor. It suggests that the slow relaxation mode of
      the shear viscosity of both liquids is governed by the density fluctuation at the
      main peak of the static structure factor, in spite of the differences in the
      details of their intermolecular interactions.

PMID- 27875874
TI  - Geometries of H2S?MI (M = Cu, Ag, Au) complexes studied by rotational
      spectroscopy: The effect of the metal atom.
AB  - Complexes formed between H2S and each of CuI, AgI, and AuI have been isolated and
      structurally characterised in the gas phase. The H2S?MI complexes (where M is the
      metal atom) are generated through laser vaporisation of a metal rod in the
      presence of a low concentration of H2S and CF3I in a buffer gas of argon
      undergoing supersonic expansion. The microwave spectra of six isotopologues of
      each of H2S?CuI, H2S?AgI and three isotopologues of H2S?AuI have been measured by
      chirped-pulse Fourier transform microwave spectroscopy. The spectra are
      interpreted to determine geometries for the complexes and to establish the values
      of structural parameters. The complexes have Cs symmetry at equilibrium and have
      a pyramidal configuration about the sulfur atom. The local C2 axis of the
      hydrogen sulfide molecule intersects the linear axis defined by the three heavy
      atoms at an angle, phi = 75.00(47) degrees  for M = Cu, phi = 78.43(76) degrees 
      for M = Ag, and phi = 71.587(13) degrees  for M = Au. The trend in the molecular
      geometries is consistent with significant relativistic effects in the gold
      containing complex. The force constant describing the interaction between the H2S
      and MI sub-units is determined from the measured centrifugal distortion constant,
      DeltaJ, of each complex. Nuclear quadrupole coupling constants, chiaa(M) and
      chiaa(I) (where M denotes the metal atom), are determined for H2S?CuI and H2S?AuI
      for the first time.

PMID- 27875875
TI  - On the accuracy of the MB-pol many-body potential for water: Interaction
      energies, vibrational frequencies, and classical thermodynamic and dynamical
      properties from clusters to liquid water and ice.
AB  - The MB-pol many-body potential has recently emerged as an accurate molecular
      model for water simulations from the gas to the condensed phase. In this study,
      the accuracy of MB-pol is systematically assessed across the three phases of
      water through extensive comparisons with experimental data and high-level ab
      initio calculations. Individual many-body contributions to the interaction
      energies as well as vibrational spectra of water clusters calculated with MB-pol
      are in excellent agreement with reference data obtained at the coupled cluster
      level. Several structural, thermodynamic, and dynamical properties of the liquid
      phase at atmospheric pressure are investigated through classical molecular
      dynamics simulations as a function of temperature. The structural properties of
      the liquid phase are in nearly quantitative agreement with X-ray diffraction data
      available over the temperature range from 268 to 368 K. The analysis of other
      thermodynamic and dynamical quantities emphasizes the importance of explicitly
      including nuclear quantum effects in the simulations, especially at low
      temperature, for a physically correct description of the properties of liquid
      water. Furthermore, both densities and lattice energies of several ice phases are
      also correctly reproduced by MB-pol. Following a recent study of DFT models for
      water, a score is assigned to each computed property, which demonstrates the high
      and, in many respects, unprecedented accuracy of MB-pol in representing all three
      phases of water.

PMID- 27875876
TI  - Dissolution dynamic nuclear polarization of deuterated molecules enhanced by
      cross-polarization.
AB  - We present novel means to hyperpolarize deuterium nuclei in 13CD2 groups at
      cryogenic temperatures. The method is based on cross-polarization from 1H to 13C
      and does not require any radio-frequency fields applied to the deuterium nuclei.
      After rapid dissolution, a new class of long-lived spin states can be detected
      indirectly by 13C NMR in solution. These long-lived states result from a sextet
      triplet imbalance (STI) that involves the two equivalent deuterons with spin I =
      1. An STI has similar properties as a triplet-singlet imbalance that can occur in
      systems with two equivalent I = 12 spins. Although the lifetimes TSTI are shorter
      than T1(Cz), they can exceed the life-time T1(Dz) of deuterium Zeeman
      magnetization by a factor of more than 20.

PMID- 27875877
TI  - Communication: XFAIMS-eXternal Field Ab Initio Multiple Spawning for electron
      nuclear dynamics triggered by short laser pulses.
AB  - Attoscience is an emerging field where attosecond pulses or few cycle IR pulses
      are used to pump and probe the correlated electron-nuclear motion of molecules.
      We present the trajectory-guided eXternal Field Ab Initio Multiple Spawning
      (XFAIMS) method that models such experiments "on-the-fly," from laser pulse
      excitation to fragmentation or nonadiabatic relaxation to the ground electronic
      state. For the photoexcitation of the LiH molecule, we show that XFAIMS gives
      results in close agreement with numerically exact quantum dynamics simulations,
      both for atto- and femtosecond laser pulses. We then show the ability of XFAIMS
      to model the dynamics in polyatomic molecules by studying the effect of nuclear
      motion on the photoexcitation of a sulfine (H2CSO).

PMID- 27875878
TI  - Publisher's Note: "Ab initio study of vacancy formation in cubic LaMnO3 and
      SmCoO3 as cathode materials in solid oxide fuel cells" [J. Chem. Phys. 145,
      014703 (2016)].

PMID- 27875879
TI  - Guided ion beam and theoretical studies of the reactions of Re+, Os+, and Ir+
      with CO.
AB  - The kinetic-energy dependences of the reactions M+ + CO where M+ = Re+, Os+, and
      Ir+ are studied using guided ion-beam tandem mass spectrometry. Formation of both
      MO+ and MC+ was observed in endothermic processes for all three metals. Modeling
      of the data provides thresholds that yield 0 K bond dissociation energies (BDEs,
      in eV) of 4.67 +/- 0.09 (Re+-O), 4.82 +/- 0.14 (Os+-O), 4.25 +/- 0.11 (Ir+-O),
      5.13 +/- 0.12 (Re+-C), 6.14 +/- 0.14 (Os+-C), and 6.58 +/- 0.12 (Ir+-C). These
      BDEs agree well with literature values within experimental uncertainties
      demonstrating that ground state products are formed for all cases even though
      some of the reactions are formally spin forbidden. Quantum mechanical
      calculations at several levels of theory and using several basis sets were
      performed for MC+ and MO+ (with comparable results taken from the literature in
      some cases). B3LYP and CCSD(T) calculated ground state BDEs agree reasonably well
      with experimental values. The ground states in B3LYP and CCSD(T)/CBS calculations
      are Sigma-3 (ReC+), Delta2 (OsC+), and Sigma+1 or Delta3 (IrC+) after including
      spin-orbit considerations. Relaxed potential energy surfaces (PESs) for the M+ +
      CO reactions show crossings between surfaces of different spin states such that
      products can be formed with no barriers in excess of the substantial
      endothermicities. Unlike results for these metal cations reacting with O2, the
      kinetic energy dependent cross sections for the formation of MO+ in the M+ + CO
      reactions exhibit only one feature. Reasons for this differential behavior are
      discussed in detail.

PMID- 27875880
TI  - Measured electrical charge of SiO2 in polar and nonpolar media.
AB  - We present measurements of the net electrical surface charge of silicon dioxide
      (SiO2) in contact with solvents of dielectric constants between 5 and 80. Our
      experimental approach relies on observing the thermal motion of single silica
      particles confined in an electrostatic fluidic trap created by SiO2 surfaces. We
      compare the experimentally measured functional form of the trapping potential
      with that from free energy calculations and thereby determine the net surface
      charge in the system. Our findings clearly demonstrate that contrary to popular
      perception, even in the absence of surfactants, the net electrical charge of
      ionizable surfaces in contact with apolar solvents can be large enough to lead to
      significant repulsive forces. A charge regulation model for SiO2 surfaces with a
      single tunable parameter explains our measurements. This model may find general
      applicability in estimating the net charge of ionizable surfaces, given system
      parameters such as the dissociation or association constants of the ionizable
      groups and the pH, ionic strength, and dielectric constant of the solvent phase.

PMID- 27875881
TI  - Communication: "Position" does matter: The photofragmentation of the
      nitroimidazole isomers.
AB  - A combined experimental and theoretical approach has been used to disentangle the
      fundamental mechanisms of the fragmentation of the three isomers of
      nitroimidazole induced by vacuum ultra-violet (VUV) radiation, namely, 4-, 5-,
      and 2-nitroimidazole. The results of mass spectrometry as well as photoelectron
      photoion coincidence spectroscopy display striking differences in the radiation
      induced decomposition of the different nitroimidazole radical cations. Based on
      density functional theory (DFT) calculations, a model is proposed which fully
      explains such differences, and reveals the subtle fragmentation mechanisms
      leading to the release of neutral species like NO, CO, and HCN. Such species have
      a profound impact in biological media and may play a fundamental role in
      radiosensitising mechanisms during radiotherapy.

PMID- 27875882
TI  - On the feasibility of designing hyperalkali cations using superalkali clusters as
      ligands.
AB  - The possibility of using superalkali clusters instead of alkali atoms as ligands
      to design a class of cationic compounds, referred to as hyperalkali cations, has
      been examined by using gradient-corrected density functional theory. By taking
      typical superalkalis (FLi2, OLi3, and NLi4) as examples, a series of hyperalkali
      cations ML2+ [M = (super)halogen; L = superalkali] have been constructed and
      investigated. Calculational results show that all the superalkali moieties
      preserve their geometric and electronic integrity in these proposed cations. The
      stability of these studied cations is guaranteed by the strong ionic bonds
      between superalkali ligand and (super)halogen core, as well as their large
      highest occupied molecular orbital-lowest unoccupied molecular orbital gaps and
      positive dissociation energies. In particular, all these proposed cations possess
      lower vertical electron affinities (2.36-3.56 eV) than those of their
      corresponding cationic superalkali ligands, verifying their hyperalkali nature.
      We, therefore, hope that this study will provide an approach to obtain new
      species with excellent reducing capability by utilizing various superalkalis as
      building blocks.

PMID- 27875883
TI  - Electronic ground state of Ni2.
AB  - The Phi9/24 ground state of the Ni2+ diatomic molecular cation is determined
      experimentally from temperature and magnetic-field-dependent x-ray magnetic
      circular dichroism spectroscopy in a cryogenic ion trap, where an electronic and
      rotational temperature of 7.4+/-0.2 K was reached by buffer gas cooling of the
      molecular ion. The contribution of the spin dipole operator to the x-ray magnetic
      circular dichroism spin sum rule amounts to 7Tz=0.17+/-0.06MUB per atom,
      approximately 11% of the spin magnetic moment. We find that, in general,
      homonuclear diatomic molecular cations of 3d transition metals seem to adopt
      maximum spin magnetic moments in their electronic ground states.

PMID- 27875884
TI  - Non-adiabatic transition probability dependence on conical intersection
      topography.
AB  - We derive a closed form analytical expression for the non-adiabatic transition
      probability for a distribution of trajectories passing through a generic conical
      intersection (CI), based on the Landau-Zener equation for the non-adiabatic
      transition probability for a single straight-line trajectory in the CI's
      vicinity. We investigate the non-adiabatic transition probability's variation
      with topographical features and find, for the same crossing velocity, no
      intrinsic difference in efficiency at promoting non-adiabatic decay between
      peaked and sloped CIs, a result in contrast to the commonly held view. Any
      increased efficiency of peaked over sloped CIs is thus due to dynamical effects
      rather than to any increased transition probability of topographical origin. It
      is also shown that the transition probability depends in general on the direction
      of approach to the CI, and that the coordinates' reduced mass can affect the
      transition probability via its influence on the CI topography in mass-scaled
      coordinates. The resulting predictions compare well with surface hopping
      simulation results.

PMID- 27875885
TI  - Morphology of symmetric ABCD tetrablock quaterpolymers studied by Monte Carlo
      simulation.
AB  - Morphology of symmetric ABCD tetrablock quaterpolymers in melt was studied by the
      Monte Carlo (MC) simulation, where the volume fractions of the block chains, f,
      kept the relationships of fA=fD and fB=fC, and the volume fraction of the two mid
      blocks phi was defined as phi=fB+fC. Previous self-consistent field theory for
      ABCD reported morphological change including several structures; however, the
      scope was limited within a two-dimensional system. To the contrary, in this
      paper, MC simulations were carried out in three dimensions with changing the phi
      value finely, which resulted in finding a tetracontinuous structure in the range
      of 0.625<=phi<=0.75. Moreover the tetracontinuous structure has been found to be
      the gyroid structure, and the mean curvature of the B/C interface is nearly zero.
      We concluded that the B/C interface must be the Schoen gyroid surface, one of
      three-dimensional periodic minimal surfaces. The geometrical nature of the A/B
      interface should be equivalent to that of the C/D interface, and they stand as
      level surfaces to the Schoen gyroid surface.

PMID- 27875886
TI  - An accurate potential model for the a3Sigmau+ state of the alkali dimers Na2, K2,
      Rb2, and Cs2.
AB  - A modified semi-empirical Tang-Toennies potential model is used to describe the
      a3Sigmau+ potentials of the alkali dimers. These potentials are currently of
      interest in connection with the laser manipulation of the ultracold alkali gases.
      The fully analytical model is based on three experimental parameters, the well
      depth De, well location Re, and the harmonic vibrational frequency omegae of
      which the latter is only slightly optimized within the range of the literature
      values. Comparison with the latest spectroscopic data shows good agreement for
      Na2, K2, Rb2, and Cs2, comparable to that found with published potential models
      with up to 55 parameters. The differences between the reduced potential of Li2
      and the conformal reduced potentials of the heavier dimers are analyzed together
      with why the model describes Li2 less accurately. The new model potential
      provides a test of the principle of corresponding states and an excellent first
      order approximation for further optimization to improve the fits to the
      spectroscopic data and describe the scattering lengths and Feshbach resonances at
      ultra-low temperatures.

PMID- 27875887
TI  - The dynamics of copper intercalated molybdenum ditelluride.
AB  - Layered transition metal dichalcogenides are emerging as key materials in
      nanoelectronics and energy applications. Predictive models to understand their
      growth, thermomechanical properties, and interaction with metals are needed in
      order to accelerate their incorporation into commercial products. Interatomic
      potentials enable large-scale atomistic simulations connecting first principle
      methods and devices. We present a ReaxFF reactive force field to describe
      molybdenum ditelluride and its interactions with copper. We optimized the force
      field parameters to describe the energetics, atomic charges, and mechanical
      properties of (i) layered MoTe2, Mo, and Cu in various phases, (ii) the
      intercalation of Cu atoms and small clusters within the van der Waals gap of
      MoTe2, and (iii) bond dissociation curves. The training set consists of an
      extensive set of first principles calculations computed using density functional
      theory (DFT). We validate the force field via the prediction of the adhesion of a
      single layer MoTe2 on a Cu(111) surface and find good agreement with DFT results
      not used in the training set. We characterized the mobility of the Cu ions
      intercalated into MoTe2 under the presence of an external electric field via
      finite temperature molecular dynamics simulations. The results show a significant
      increase in drift velocity for electric fields of approximately 0.4 V/A  and that
      mobility increases with Cu ion concentration.

PMID- 27875888
TI  - Interaction and charge transfer between dielectric spheres: Exact and approximate
      analytical solutions.
AB  - We present exact analytical solutions for charge transfer reactions between two
      arbitrarily charged hard dielectric spheres. These solutions, and the
      corresponding exact ones for sphere-sphere interaction energies, include sums
      that describe polarization effects to infinite orders in the inverse of the
      distance between the sphere centers. In addition, we show that these exact
      solutions may be approximated by much simpler analytical expressions that are
      useful for many practical applications. This is exemplified through calculations
      of Langevin type cross sections for forming a compound system of two colliding
      spheres and through calculations of electron transfer cross sections. We find
      that it is important to account for dielectric properties and finite sphere sizes
      in such calculations, which for example may be useful for describing the
      evolution, growth, and dynamics of nanometer sized dielectric objects such as
      molecular clusters or dust grains in different environments including
      astrophysical ones.

PMID- 27875889
TI  - A new wavefunction hierarchy for interacting geminals.
AB  - A new truncation scheme for non-orthogonal antisymmetrized products of
      interacting geminals (APIG) is introduced based on antisymmetrized products of
      strongly orthogonal geminals (APSG). This wavefunction hierarchy of interacting
      geminals (IG) allows us to gradually increase the accuracy at which the ground
      state of a seniority-zero Hamiltonian can be estimated, ranging from APSG up to
      approximation-free APIG. Mathematical expressions for the lowest four orders
      (IG0, IG1, IG2, and IG3) are given explicitly and the computational cost to
      evaluate their transition density matrix is verified to scale only cubically with
      system size. Exemplary numerical calculations indicate that already a very early
      truncation level leads to results virtually identical to APIG.

PMID- 27875890
TI  - Elucidating the structure of merocyanine dyes with the ASEC-FEG method. Phenol
      blue in solution.
AB  - The electronic structure of phenol blue (PB) was investigated in several protic
      and aprotic solvents, in a wide range of dielectric constants, using atomistic
      simulations. We employed the sequential QM/MM and the free energy gradient
      methods to optimize the geometry of PB in each solvent at the MP2/aug-cc-pVTZ
      level. The ASEC mean field is used to include the ensemble average of the solute
      solvent interaction into the molecular hamiltonian, both for the geometry
      optimization and for the calculations of the electronic properties. We found that
      the geometry of PB changes considerably, from a polyene-like structure in
      nonpolar solvents to a cyanine-like in water. Moreover, and quite interestingly,
      in protic solvents with higher dielectric constant than water, the structure of
      the molecule is less affected and lies in an intermediate state. The results
      illustrate the important role played by hydrogen bonds in the conformation of
      merocyanine dyes.

PMID- 27875891
TI  - The Uhlenbeck-Ford model: Exact virial coefficients and application as a
      reference system in fluid-phase free-energy calculations.
AB  - The Uhlenbeck-Ford (UF) model was originally proposed for the theoretical study
      of imperfect gases, given that all its virial coefficients can be evaluated
      exactly, in principle. Here, in addition to computing the previously unknown
      coefficients B11 through B13, we assess its applicability as a reference system
      in fluid-phase free-energy calculations using molecular simulation techniques.
      Our results demonstrate that, although the UF model itself is too soft,
      appropriately scaled Uhlenbeck-Ford (sUF) models provide robust reference systems
      that allow accurate fluid-phase free-energy calculations without the need for an
      intermediate reference model. Indeed, in addition to the accuracy with which
      their free energies are known and their convenient scaling properties, the fluid
      is the only thermodynamically stable phase for a wide range of sUF models. This
      set of favorable properties may potentially put the sUF fluid-phase reference
      systems on par with the standard role that harmonic and Einstein solids play as
      reference systems for solid-phase free-energy calculations.

PMID- 27875892
TI  - A coarse-grained DNA model for the prediction of current signals in DNA
      translocation experiments.
AB  - We present an implicit solvent coarse-grained double-stranded DNA (dsDNA) model
      confined to an infinite cylindrical pore that reproduces the experimentally
      observed current modulations of a KaCl solution at various concentrations. Our
      model extends previous coarse-grained and mean-field approaches by incorporating
      a position dependent friction term on the ions, which Kesselheim et al. [Phys.
      Rev. Lett. 112, 018101 (2014)] identified as an essential ingredient to correctly
      reproduce the experimental data of Smeets et al. [Nano Lett. 6, 89 (2006)]. Our
      approach reduces the computational effort by orders of magnitude compared with
      all-atom simulations and serves as a promising starting point for modeling the
      entire translocation process of dsDNA. We achieve a consistent description of the
      system's electrokinetics by using explicitly parameterized ions, a friction term
      between the DNA beads and the ions, and a lattice-Boltzmann model for the
      solvent.

PMID- 27875893
TI  - High pressure chemistry of thioaldehydes: A first-principles molecular dynamics
      study.
AB  - First-principles molecular dynamics simulations are used to investigate the
      chemical behavior of bulk thioacetaldehyde (MeC(H)S) in response to changes in
      pressure, P. The simulations show that these molecules oligomerize in response to
      applied P. Oligomerization is initiated through C-S bond formation, with
      constrained dynamics simulations showing that the barrier to this reaction step
      is lowered significantly by applied P. Subsequent reactions involving the
      formation of additional C-S bonds or radical processes that lead to S-S and C-C
      bonds lengthen the oligomers. Oligomerization is terminated through proton
      transfer or the formation of rings. The mechanistic details of all reactions are
      examined. The results indicate that the P-induced reactivity of the MeC(H)S-based
      system differs significantly from that of analogous MeC(H)O-based systems, which
      have been reported previously. Comparison with the MeC(H)O study shows that
      replacing oxygen with sulfur significantly lowers the P required to initiate
      oligomerization (from 26 GPa to 5 GPa), increases the types of reactions in which
      systems of this type can take part, and increases the variety of products formed
      through these reactions. These differences can be explained in terms of the
      electronic structures of these systems, which may be useful for certain high P
      applications.

PMID- 27875894
TI  - Properties of the two-dimensional heterogeneous Lennard-Jones dimers: An integral
      equation study.
AB  - Structural and thermodynamic properties of a planar heterogeneous soft dumbbell
      fluid are examined using Monte Carlo simulations and integral equation theory.
      Lennard-Jones particles of different sizes are the building blocks of the dimers.
      The site-site integral equation theory in two dimensions is used to calculate the
      site-site radial distribution functions and the thermodynamic properties.
      Obtained results are compared to Monte Carlo simulation data. The critical
      parameters for selected types of dimers were also estimated and the influence of
      the Lennard-Jones parameters was studied. We have also tested the correctness of
      the site-site integral equation theory using different closures.

PMID- 27875895
TI  - Monitoring coherent electron wave packet excitation dynamics by two-color
      attosecond laser pulses.
AB  - We propose a method to monitor coherent electron wave packet (CEWP) excitation
      dynamics with two-color attosecond laser pulses. Simulations are performed on
      aligned H2+ by numerically solving the three-dimensional time-dependent
      Schrodinger equation with combinations of a resonant linearly polarized lambdal=
      100/70 nm pump pulse and a circularly polarized lambdac=5 nm attosecond probe
      pulse. It is found that time dependent diffraction patterns in molecular frame
      photoelectron angular distributions (MFPADs) produced by the circular probe pulse
      exhibit sensitivity to the molecular alignments and time-dependent geometry of
      the CEWPs during and after the coherent excitation between the ground and excited
      states induced by the linear pump pulse. The time dependent MFPADs are described
      by an ultrafast diffraction model for the ionization of the bound CEWPs.

PMID- 27875896
TI  - Publisher's Note: "Density-based cluster algorithms for the identification of
      core sets" [J. Chem. Phys. 145, 164104 (2016)].

PMID- 27875897
TI  - Isotropic-nematic transition and cholesteric phases of helical Yukawa rods.
AB  - We present a Monte Carlo simulation study of helical Yukawa rods as a model for
      chiral liquid crystal mesogens. To simulate the cholesteric phase, we introduce a
      new simulation method that uses soft walls and self-determined boundary
      conditions. We observe that the isotropic-nematic phase transition is shifted to
      lower volume fractions with decreasing salt concentration as well as with
      increasing internal pitch of the rods. For particular sets of interaction
      parameters, the sense of the cholesteric pitch inverts, i.e., depending on
      concentration, mesogens of a given handedness can produce cholesteric phases of
      both chiral senses.

PMID- 27875898
TI  - Reflection of light by anisotropic molecular crystals including exciton
      polaritons and spatial dispersion.
AB  - A theory for the reflection of light by molecular crystals is described, which
      reproduces the minimum within the reflection band that is observed
      experimentally. The minimum in reflection is related to the excitation of
      polaritons in the crystal. The theory involves reformulation of the boundary
      conditions for electromagnetic waves at the interface between vacuum and
      material. The material is modeled by a cubic lattice of oriented Lorentz
      oscillators. By requiring uniformity of gauge of the electromagnetic potential
      across the interface between vacuum and the dipole lattice, the need for
      additional boundary conditions is obviated. The frequency separation between the
      maxima in reflectance on both sides of the minimum allows for the extraction of a
      plasma frequency. The plasma frequencies extracted from reflection spectra are
      compared to the plasma frequencies calculated directly from structural data on
      the crystals and the oscillator strengths of the constituent molecules. A good
      agreement between extracted and calculated plasma frequency is obtained for a set
      of 11 dye molecules.

PMID- 27875899
TI  - Amelioration of energy metabolism by melatonin in skeletal muscle of rats with
      LPS induced endotoxemia.
AB  - In the literature, few studies have investigated the effects of melatonin on
      energy metabolism in skeletal muscle in endotoxemia. We investigated the effects
      of melatonin on tissue structure, energy metabolism in skeletal muscle, and
      antioxidant level of rats with endotoxemia. We divided rats into 4 groups,
      control, lipopolysaccharide (LPS) (20 mg/kg, i.p., single dose), melatonin (10
      mg/kg, i.p., three times), and melatonin + LPS. Melatonin was injected i.p. 30
      min before and after the 2nd and 4th hours of LPS injection. Antioxidant status
      was determined by glutathione (GSH) measurement in the blood. Muscle tissue was
      stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH), and
      cytochrome oxidase (COX) and histological scored. Also the sections were then
      stained with hematoxylin and eosin. The stained sections were visualized and
      photographed. Creatine, creatine phosphate, adenosine triphosphate (ATP),
      adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels were
      investigated using high performance liquid chromatography (HPLC) in muscle
      tissue. In the Melatonin + LPS group, blood GSH levels were increased compared
      with the LPS group (P<0.01). Melatonin reduced myopathic changes in the LPS group
      according to the histopathologic findings. In addition, ATP values were increased
      compared with the LPS group (P<0.05). Our findings showed melatonin treatment
      prevented muscle damage by increasing ATP and GSH levels in rats with LPS induced
      endotoxemia.

PMID- 27875900
TI  - Effects of necrostatin-1, an inhibitor of necroptosis, and its inactive analogue
      Nec-1i on basal cardiovascular function.
AB  - Inhibition of receptor-interacting serine/threonine-protein kinase 1 (RIP1) by
      necrostatin-1 (Nec-1) alleviates cardiac injury due to prevention of necroptotic
      cell death. Its inactive analogue necrostatin-1i (Nec-1i), lacking RIP1 activity,
      serves as a suitable control. It is unknown if these agents influence the heart
      function in the absence of damaging stimuli. For this purpose, we measured
      intraarterial blood pressure (systolic - sBP and diastolic - dBP) and ECG
      parameters after a bolus administration of Nec-1 and Nec-1i in rats during 30
      min. Nec-1, unlike Nec-1i, increased sBP and dBP, as well as heart rate reaching
      the peak at 20 min. The P wave duration tended to be decreased and the duration
      of the PR interval was shortened by Nec-1 indicating faster conduction of the
      impulses through atria to the ventricles. The drugs did not influence the QTc
      interval duration and no episode of ventricular arrhythmia was observed. In
      summary, Nec-1 temporarily modulates blood pressure and electrical function of
      the healthy heart. These effects of Nec-1 are likely due to its off-target action
      or RIP1 has an important role in the regulation of cardiovascular function
      independently of its action on the necroptotic pathway.

PMID- 27875901
TI  - Reducing radiation-related morbidity in the treatment of nasopharyngeal
      carcinoma.
AB  - While radiation therapy is the mainstay of treatment for nasopharyngeal
      carcinoma, the anatomic location of the nasopharynx in close proximity to
      radiation-sensitive organs such as the salivary glands, optic nerves and chiasm,
      cochlea, brainstem and temporal lobes presents a special challenge. Technological
      approaches to reducing the morbidity of nasopharyngeal cancer irradiation have
      been historically successful with the evolution from 2D techniques to
      increasingly conformal forms of radiation therapy. This report reviews normal
      tissue dose constraints and major considerations in target delineation for
      patients with nasopharyngeal cancer in the intensity-modulated radiation therapy
      era. Furthermore, this report discusses more contemporary approaches to toxicity
      reduction such as the judicious reduction or omission of radiation to low-risk
      regions and the potential role of particle beam therapy.

PMID- 27875902
TI  - Nuisance Regression of High-Frequency Functional Magnetic Resonance Imaging Data:
      Denoising Can Be Noisy.
AB  - Recently, emerging studies have demonstrated the existence of brain resting-state
      spontaneous activity at frequencies higher than the conventional 0.1 Hz. A few
      groups utilizing accelerated acquisitions have reported persisting signals beyond
      1 Hz, which seems too high to be accommodated by the sluggish hemodynamic process
      underpinning blood oxygen level-dependent contrasts (the upper limit of the
      canonical model is ~0.3 Hz). It is thus questionable whether the observed high
      frequency (HF) functional connectivity originates from alternative mechanisms
      (e.g., inflow effects, proton density changes in or near activated neural tissue)
      or rather is artificially introduced by improper preprocessing operations. In
      this study, we examined the influence of a common preprocessing step-whole-band
      linear nuisance regression (WB-LNR)-on resting-state functional connectivity
      (RSFC) and demonstrated through both simulation and analysis of real dataset that
      WB-LNR can introduce spurious network structures into the HF bands of functional
      magnetic resonance imaging (fMRI) signals. Findings of present study call into
      question whether published observations on HF-RSFC are partly attributable to
      improper data preprocessing instead of actual neural activities.

PMID- 27875904
TI  - Timing of rectal cancer surgery following neoadjuvant chemoradiation: how close
      are we to striking an equipoise?

PMID- 27875903
TI  - Correlates of sexual-risk behaviors among young black MSM: implications for
      clinic-based counseling programs.
AB  - This study applied an 8-item index of recent sexual-risk behaviors to young Black
      men who have sex with men (YBMSM) and evaluated the distribution for normality.
      The distribution was tested for associations with possible antecedents of sexual
      risk. YBMSM (N = 600), aged 16-29 years, were recruited from a sexually
      transmitted infection clinic, located in the southern US. Men completed an
      extensive audio computer-assisted self-interview. Thirteen possible antecedents
      of sexual risk, as assessed by the index, were selected for analyses. The 8-item
      index formed a normal distribution with a mean of 4.77 (SD = 1.77). In adjusted
      analyses, not having completed education beyond high school was associated with
      less risk, as was having sex with females. Conversely, meeting sex partners
      online was associated with greater risk, as was reporting that sex partners were
      drunk during sex. The obtained normal distribution of sexual-risk behaviors
      suggests a corresponding need to "target and tailor" clinic-based counseling and
      prevention services for YBMSM. Avoiding sex when partners are intoxicated may be
      an especially valuable goal of counseling sessions.

PMID- 27875906
TI  - The therapeutic effects of cholecystokinin octapeptide on rat liver and kidney
      microcirculation disorder in endotoxic shock.
AB  - OBJECTIVES: Our previous studies demonstrated that pretreatment with
      cholecystokinin octapeptide (CCK-8) could alleviate endothelial cell injury and
      reverse abnormal vascular reactivity as well as reduce LPS-induced inflammation
      cascades, which suggested that CCK-8 plays a potential role in anti-endotoxic
      shock. The present study aimed to determine the therapeutic effects of CCK-8 on
      rat liver and kidney microcirculatory perfusion disorder under endotoxic shock
      (ES) conditions. MATERIALS AND METHODS: Sprague-Dawley rats were induced to
      lethal endotoxic shock by an injection of LPS. CCK-8 was administered 30 min
      after LPS injection. Either a specific CCK-1R antagonist or CCK-2R antagonist was
      injected before CCK-8 treatment. The mean arterial pressure (MAP), liver and
      kidney microcirculatory perfusion, and heart rate (HR) were recorded with a multi
      channel data acquisition system. The serum concentrations of alanine
      aminotransferase (ALT) and creatinine (Cr) were measured, and the
      histopathological changes in the liver and kidney were also observed. RESULTS:
      Administration of CCK-8 significantly delayed the LPS-induced decreases in not
      only the liver and kidney microcirculation perfusion but also the HR. The
      pathology changes induced by LPS in the liver and kidney tissues were
      significantly mitigated in the LPS + CCK-8 group. The levels of ALT and Cr in the
      serum of the LPS + CCK-8 group were obviously lower than those in the LPS group.
      In addition, the specific antagonist at the CCK-2 receptor (CCK-2R) abrogated the
      action of CCK-8 significantly. CONCLUSIONS: These results indicated that CCK-8
      has potential therapeutic effects on microcirculation failure in an ES rat model
      via the CCK-2 receptor.

PMID- 27875905
TI  - Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT
      Connection and RNase H Domains from Patients Under Virological Failure in Brazil.
AB  - Mutations in the connection and RNase H C-terminal reverse transcriptase (RT)
      domains of HIV-1 have been shown to impact drug resistance to RT inhibitors.
      However, their impact in the context of non-B subtypes has been poorly assessed.
      This study aimed to characterize resistance-related mutations in the C-terminal
      portions of RT in treatment-failing patients from southern Brazil, a region with
      endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed
      from 280 infected subjects, and genomic regions were analyzed by polymerase chain
      reaction, DNA sequencing, and phylogenetic analysis. Two novel mutations, M357R
      and E529D, were evidenced in Brazilian HIV-1C strains from treatment-failing
      patients. In global viral isolates of subjects on treatment, M357R was selected
      in HIV-1C and CRF01_AE and E529D was selected in HIV-1 subtype B (HIV-1B). While
      most C-terminal RT mutations described for HIV-1B also occur in HIV-1C, this work
      pinpointed novel mutations that display subtype-specific predominance or
      occurrence.

PMID- 27875907
TI  - Chemical constituents from the roots of Tripterygium wilfordii and their
      cytotoxic activity.
AB  - In our ongoing search for bioactive constituents, a new sesquiterpene polyol
      ester, named triptersinine U (1), together with five known triterpenes (2-6) and
      seven sesquiterpene pyridine alkaloids (7-13), were isolated from the roots of
      Tripterygium wilfordii Hook. f. Their chemical structures were elucidated using
      extensive spectroscopic analyses, including 1D and 2D NMR, and HRESIMS, as well
      as comparison with previously reported data. Cytotoxic activities of all
      compounds 1-13 were evaluated against six human tumor cell lines (HepG2, Hep3B,
      Bcap37, U251, MCF-7 and A549) using the MTT in vitro assay. The results showed
      that triterpenes exhibited moderate cytotoxic activities toward the tested cell
      lines.

PMID- 27875908
TI  - Short Communication: The Impact of Viral Suppression and Viral Breakthrough on
      Limited-Antigen Avidity Assay Results in Individuals with Clade B HIV Infection.
AB  - We analyzed the impact of HIV viral load on the performance of a limiting antigen
      avidity enzyme immunoassay (LAg-Avidity assay) and determined if this assay could
      be used to identify viral breakthrough. Three groups of samples were tested: (1)
      18 individuals (30 samples) previously identified as elite suppressors; (2) 18
      individuals (72 samples) who were continually suppressed on antiretroviral
      treatment (ART) with 1 sample before and 2-6 samples (one/year) after ART
      initiation; and (3) 20 individuals (179 samples) on ART who had evidence of viral
      breakthrough (>400 copies/ml) with subsequent viral suppression. Elite
      suppressors had the lowest LAg-Avidity assay values. Among those who were
      continually suppressed on ART, 83% (15/18) had LAg-Avidity assay values that
      decreased over time. Although the LAg-Avidity assay on a single sample cannot
      identify when a viral breakthrough occurs, paired longitudinal samples could
      identify viral breakthrough (sensitivity: 65%, specificity: 84%).

PMID- 27875909
TI  - High HIV-Trypanosoma cruzi Coinfection Levels in Vulnerable Populations in Buenos
      Aires, Argentina.

PMID- 27875910
TI  - Cancer pain: a review of epidemiology, clinical quality and value impact.
AB  - Cancer-related pain, reported by more than 70% of patients, is one of the most
      common and troublesome symptoms affecting patients with cancer. Despite the
      availability of effective treatments, cancer-related pain may be inadequately
      controlled in up to 50% of patients. With the growing focus on 'value'
      (healthcare outcomes achieved per dollar spent) in healthcare, the management of
      cancer-related pain has assumed novel significance in recent years. Data from
      initiatives that assess the quality of pain management in clinical practice have
      shown that effective management of cancer-related pain improves patient-perceived
      value of cancer treatment. As a result, assessment and effective management of
      cancer-related pain are now recognized as important measures of value in cancer
      care.

PMID- 27875911
TI  - Identification of the optimal visual recording system in open abdominal surgery -
      a prospective observational study.
AB  - INTRODUCTION: Current methodologies used to record and render the surgeon's point
      of view in open operative surgery remain limited. Chief among these limitations
      is a failure to demonstrate, in high definition and magnification, the planar
      roadmap that surgeons utilise in colorectal surgery. The high magnification and
      high resolution views provided during laparoscopic surgery simultaneously capture
      the planar road map and surgeon's point of view. We developed an arm-mounted
      external laparoscope (exoscope) system and compared its performance against
      multiple standard recording modalities. METHODS: Following ethical approval and
      informed consent, open colorectal procedures were recorded using five separate
      methodologies. Each methodology was assessed and compared. RESULTS: Most of the
      methodologies utilised scored poorly at one if not more levels. The arm-mounted
      external laparoscope (exoscope) scored highest in rendering the surgeon's point
      of view while simultaneously achieving high resolution and high magnification
      rendition of operative field (p < .001). This methodology was tested in a number
      of operative contexts within which it reproducibly and consistently scored
      highly. CONCLUSIONS: The arm-mounted exoscope is the optimal means of rendering
      the surgeon's point of view of anatomic planes during open colorectal surgery.

PMID- 27875912
TI  - Assessing time to first treatment in early chronic lymphocytic leukemia (CLL): a
      comparative performance analysis of five prognostic models with inclusion of CLL
      international prognostic index (CLL-IPI).

PMID- 27875913
TI  - Development and optimization of a meloxicam/beta-cyclodextrin complex for orally
      disintegrating tablet using statistical analysis.
AB  - The purpose of this research was to develop an inclusion complex of meloxicam
      (MEL)/beta-cyclodextrin (beta-CD) incorporated into an orally disintegrating
      tablet (ODT), using statistical analysis to optimize the ODT formulation based on
      a quality by design (QbD) approach. MEL/beta-CD complexation was performed by
      kneading, co-precipitation and spray drying methods under different molar ratios.
      Fourier transform infrared spectroscopy, X-ray diffraction and thermal analysis
      were utilized to evaluate the complexes. A central composite design (alpha = 2)
      was applied to optimize and assess the influence of Primojel, Primellose and
      crushing strength (CS) as independent variables on tablet friability,
      disintegration behavior, wicking properties and drug release. The spray drying
      method induced formation of an amorphous complex and enhanced solubility and drug
      release of MEL. Furthermore, a QbD-based statistical analysis was successfully
      utilized to optimize the ODT formulation. Primojel, Primellose and CS showed
      unique main effects and interactions at different levels. CS was the dominant
      factor, affecting friability, disintegration behavior and drug release, while
      wicking properties were affected by Primojel and its interaction with Primellose.
      Therefore, according to the overlay plot, CS was dominant factor in determining
      the optimum region based on a QbD approach.

PMID- 27875914
TI  - Second generation antipsychotics in 'real-life' paediatric patients. Adverse drug
      reactions and clinical outcomes of drug switch.
AB  - OBJECTIVE: Gap in knowledge on benefit/risk ratio of second generation
      antipsychotics (SGA) in the paediatric population represents a challenge for the
      scientific community. This study aims to analyse all suspected adverse drug
      reactions (ADRs) to SGA observed during the study period; compare the safety
      profiles of risperidone and aripiprazole; evaluate the effect of switching from
      risperidone to aripiprazole or to a first generation antipsychotic (FGA).
      METHODS: Prospective analysis of spontaneously reported ADRs concerning 184
      paediatric outpatients between 2012 and 2014.; clinical outcomes of drug switch
      were evaluated. RESULTS: Out of the 184 patients, 130 experienced at least one
      ADR; ADRs were usually not serious and more frequently associated with
      aripiprazole. Switching to aripiprazole was associated with better results than
      switching to FGAs in the Clinical Global Impression scale- Efficacy (CGI-E)
      scores (p = 0.018), Disturbed behaviour checklist-parents (DBC-P) self-absorption
      subscale (p = 0.010); only a trend for difference between changing to
      aripiprazole vs FGAs in the DBC-P total score (p = 0.054) and social relating
      subscale (p = 0.053) was observed. CONCLUSIONS: SGAs safety data were consistent
      with the ones already known; however, there is still a need to improve the
      knowledge in pharmacovigilance field among clinicians. Switching to aripiprazole
      may be a valid alternative to risperidone.

PMID- 27875915
TI  - Efficacy and safety of insulin-GLP-1 receptor agonists combination in type 2
      diabetes mellitus: a systematic review.
AB  - INTRODUCTION: Attaining optimal glycemic targets in patients with type 2 diabetes
      is often hard and compromised by the shortcomings of the several treatments.
      Areas covered: When glycemic levels are not adequately controlled, an association
      of GLP-1 receptor agonists and insulin therapy can be adopted. In order to assess
      the benefit/risk profile of this combination therapy, a literature search of
      randomized clinical trials was performed.Eighteen trials matched the inclusion
      criteria. In 10 studies, GLP-1 receptor agonists were added on to an existing
      regimen, whereas insulin added to an existing GLP-1 receptor agonists regimen
      occurred in 2 studies. Six studies compared GLP-1 receptor agonists with short
      acting insulin as a treatment strategy to intensify basal insulin therapy. Expert
      opinion: Clinical trials herein reviewed demonstrated the safety and the efficacy
      of combining GLP-1 receptor agonists with basal insulin, with most studies
      showing equal or slightly superior efficacy, as compared with the addition of
      prandial insulin, associated with weight loss and less hypoglycemia.

PMID- 27875916
TI  - New era in treatment options of chronic hepatitis C: focus on safety of new
      direct-acting antivirals (DAAs).
AB  - INTRODUCTION: New direct-acting antivirals have changed hepatitis C virus
      infection management extremely. Areas covered: The pharmacological management of
      HCV infection and the main characteristics of new DAA therapies have been
      discussed. In order to analyse safety data regarding DAA therapies, a narrative
      review was performed searching for safety results of main second generation DAAs
      pivotal and post-marketing studies. Data on main DAAs drug-drug interactions have
      also been discussed. Results of main DAAs pivotal studies revealed that these
      drugs were frequently associated to adverse events such as asthenia, headache,
      nausea, and insomnia. Although some of post-marketing studies confirmed the good
      tolerability profile already detected in the pre-marketing phase, real-world
      safety data showed that second generation DAAs can be associated to cutaneous,
      metabolic, pulmonary, hepatic, and renal adverse events. Expert opinion: Safety
      results of pivotal and post-marketing studies indicated that the most recently
      approved DAAs are well tolerated. However, considering the recent marketing
      approval of new DAAs, further observational studies and post-marketing
      surveillance activities will be necessary in order to improve the knowledge of
      their safety.

PMID- 27875917
TI  - Campania Region (Italy) spontaneous reporting system and preventability
      assessment through a case-by-case approach: a pilot study on psychotropic drugs.
AB  - OBJECTIVE: We conducted the first pilot Italian study to assess the
      preventability of adverse drug reactions involving psychotropic drugs reported
      through spontaneous reporting system from 01/07/2012 to 31/12/2014 in Campania
      Region. METHODS: Preventability was assessed, case-by-case, using an adapted
      version of the P-method. The evaluation was performed only for those reports that
      had, as suspected drug, antipsychotics, mood stabilizers, antidepressants,
      anxiolytic and/or sedative-hypnotic. RESULTS: Eighty-one cases (19.2%) out of 421
      reported during the study period were preventable. In seventy-seven (95.1%) out
      of 81 preventable cases, the underlying mechanism of the adverse drug reactions
      was dose-related, in four (4.9%) preventable cases the underlying mechanism of
      the adverse drug reactions was respectively susceptibility- (1; 1.2%), unknown-
      (1; 1.2%) and time-related (2; 2.5%). In the 81 preventable cases, 97 critical
      criteria were detected of which 29/97 (29.9%) related to healthcare
      professionals' practices, 0/97 (0.0%) to drug quality and 68/97 (70.1%) to
      patient behaviour. CONCLUSIONS: We proved that it was possible to apply and adapt
      the P-Method to assess the preventability of the adverse drug reactions involving
      psychotropic drugs, analysing individual case safety report sent through Campania
      Region spontaneous reporting system. Information acquired will be used to
      organize educational activities for both physicians and patients to promote a
      more appropriate drug use.

PMID- 27875918
TI  - Expected and actual adverse drug-drug interactions in elderly patients accessing
      the emergency department: data from the ANCESTRAL-ED study.
AB  - OBJECTIVE: This study was aimed at evaluating the frequency and describing the
      adverse drug-drug interactions (DDIs) recorded among elderly patients accessing
      the emergency department (ED). METHODS: Patients aged >=65 years, accessing the
      ED of Pisa University Hospital (Italy) from 1 January 2015 to 31 December 2015
      within the ANCESTRAL-ED program, were included in this study. 'Expected' DDIs
      were assessed using Thomson Micromedex(r). Each ED admission (discharge
      diagnosis) consistent with the signs and symptoms of an expected DDI for each
      patient was classified as an 'actual' DDI. RESULTS: Throughout the study period,
      3473 patients (3812 ED admissions, 58% females, mean age: 80.3) were recorded.
      The total number of expected DDIs was 12,578 (67 contraindicated; 3334 major;
      8878 moderate; 299 minor) detected in 2147 (62%) patients. Overall 464 expected
      DDIs were found to be consistent with the ED admission in 194 patients
      (representing 9% of patients with expected DDIs). CONCLUSIONS: More than one half
      of elderly patients admitted to ED presented at least one expected DDI at the
      time of ED presentation. However, 9% of the expected DDIs were identified as
      actual DDIs, based on the consistency of the expected event with the ED discharge
      diagnosis.

PMID- 27875919
TI  - Adverse drug reactions associated with off-label use of ketorolac, with
      particular focus on elderly patients. An analysis of the Italian
      pharmacovigilance database and a population based study.
AB  - OBJECTIVE: This study aims to evaluate the frequency of off-label use of
      ketorolac in Italy and the related suspected adverse drug reactions (ADRs)
      reported. METHODS: All the suspected cases associated with ketorolac recorded in
      the Italian Pharmacovigilance database were retrieved. Case evaluations were
      carried out in order to identify the off-label use of ketorolac. Moreover, an
      analysis of the inappropriate use of ketorolac was conducted using the 'Arianna'
      database of Caserta local health unit. RESULTS: Up to December 2014, 822 reports
      of suspected ADRs related to ketorolac were retrieved in the database. The use of
      ketorolac was classified as off-label for 553 reports and on-label for 269. Among
      the off-label cases, 58.6% were serious compared to 39.0% of on-label cases.
      Gastrointestinal events were more frequently reported with off-label use. The
      analysis of Arianna database showed that 37,729 out of 61,910 patients, were
      treated off-label. CONCLUSIONS: The off-label use of ketorolac is widespread in
      Italy. This use increases the risk of serious ADR, especially in in case of
      prolonged duration of treatment and in elderly patients. The Italian Medicine
      Agency has decided to accurately monitor the appropriate use of the drug in Italy
      and, if necessary, take measures in order to minimize the risks.

PMID- 27875920
TI  - Italian monitoring registries: a tool for a safer use of innovative drugs? Data
      from the national pharmacovigilance system.
AB  - OBJECTIVES: Our aim was to investigate the ADR reports of drugs with a monitoring
      registry (MR drugs), in particular those related to abuse/misuse, medication
      error, overdose, which might indicate an unsafe use. We compared these reports
      with those of similar drugs without a registry (non-MR drugs), thus verifying
      whether the registries could be useful tools for a safer use of innovative drugs.
      METHODS: All ADR reports included in the Italian Pharmacovigilance Network
      database from January 1st 2013 to December 31st 2015 (vaccines and literature
      cases excluded) were analysed. We compared the ADR reports of MR and non-MR drugs
      with the same ATC class at III level. RESULTS: The percentage of ADR reports with
      a completed 'Section 7' was significantly lower for MR compared to non-MR drugs
      (2.0 versus 6.2, p < 0.001). The difference concerned in particular the ADR
      reports related to abuse/misuse, medication errors and overdose. These reports,
      more strictly related to inappropriate use, were less frequent for MR drugs in
      all the considered ATC classes. CONCLUSIONS: Our study suggests that monitoring
      registries could be a useful tool for the reduction of frequency of ADRs related
      to inappropriate use, besides the control of pharmaceutical budget.

PMID- 27875921
TI  - A retrospective review of paediatric adverse drug reactions reported in Lombardy
      and Croatia from 2005 to 2013.
AB  - OBJECTIVE: to characterise the adverse drugs reactions (ADRs) reported in the
      Lombard and Croatian paediatric population and to compare data to specific
      paediatric age groups, in terms of trend, pattern and severity of ADRs,
      increasing understanding of paediatric ADRs. RESEARCH DESIGN AND METHODS: We
      selected and analysed all the spontaneous reports in which children were involved
      (0 < 18 years old) reported in the Lombardy and in Croatian pharmacovigilance
      databases from 1th March 2005 to 31th December 2013. RESULTS: 9175 ADR reports
      were reported in the Lombardy, 2457 were included in the Croatian database. The
      age groups most involved were 2-11 for both countries. The 13.2% and 40.3% of
      reports retrieved in Lombardy and Croatia were classified as serious,
      respectively. Fatalities account for 0.09% and 0.12% in Lombardy and Croatia,
      respectively. CONCLUSION: Data on serious reports reflect a similar scenario in
      terms of age range; strikingly different therapeutic subgroups were involved in
      reporting activity likely due to greater self-medication practices with
      penicillins and anti-inflammatory, analgesic and antipyretics drugs in Lombardy
      than in Croatia, highlighting the need to closely monitor this paediatric
      therapeutic area to ensure a safe use of these drugs.

PMID- 27875922
TI  - No substantial gender differences in suspected adverse reactions to ACE
      inhibitors and ARBs: results from spontaneous reporting system in Campania
      Region.
AB  - BACKGROUND: Today, there is a poor knowledge about gender differences in adverse
      drug reactions (ADRs) to cardiovascular drugs such as angiotensin-converting
      enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Therefore, the
      aim of this study was to analyze spontaneous reports of suspected ADRs induced by
      ACE-inhibitors and ARBs, between January 2001 and June 2015, recorded in a Region
      of Southern Italy (Campania Region). METHODS: We performed a descriptive gender
      related analysis of regional safety data, obtained from the spontaneous reporting
      system. RESULTS: In the considered period, 772 suspected ADRs to ACE inhibitors
      and ARBs (in monotherapy or in combination) were reported with a slightly higher
      frequency in men compared with women. In both genders, the most involved category
      was ARBs in combination, whereas the most prescribed active substance was
      ramipril. General and administration site conditions, vascular disorders and
      modification of laboratory parameters were more common in men, while respiratory
      disorders were most common in women. In 88.2% of cases, not serious ADRs were
      described more by men than women. CONCLUSIONS: This analysis suggested no
      substantial gender differences. Further studies such as randomized population
      studies or meta-analysis of ACE inhibitors and ARBs randomized studies are needed
      to clarify whether gender differences exist in the safety profile of these drugs.

PMID- 27875923
TI  - Age of onset of mesial temporal lobe epilepsy with hippocampal sclerosis: the
      effect of apolipoprotein E and febrile seizures.
AB  - PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is
      the most frequent pharmaco-resistant epilepsy. It has been associated with
      febrile seizures (FS) in childhood. Its aetiology remains unclear but genetic
      factors are involved. Apolipoprotein E (ApoE) is the main lipoprotein secreted in
      brain. It has a critical immunomodulatory function, influences neurotransmission
      and it is involved in repairing damaged neurons. ApoE epsilon4 is an isoform of
      ApoE with altered protein function, previously associated with refractoriness and
      early onset epilepsy. This study was undertaken to determine if ApoE isoforms are
      risk factors for MTLE-HS and influence clinical characteristics. METHODS: A group
      of 188 MTLE-HS patients (101 F, 87 M, mean age = 44.7 +/- 11.6 years, 100 with FS
      antecedents) was studied and compared with a group of 342 healthy individuals in
      a case-control genetic association study. Data were analysed with Pearson Chi
      squared Test or Student's t test, as appropriated. RESULTS: No differences in
      ApoE epsilon4 allelic frequencies between MTLE-HS patients and controls or
      between MTLE-HS subgroups were observed. Nevertheless, ApoE epsilon4 carriers had
      an earlier MTLE-HS onset (11.0 +/- 7.9 years in ApoE epsilon4 carriers vs. 14.4
      +/- 11.2 years in ApoE epsilon4 non-carriers p < 0.05). Additionally, we observed
      that MTLE-HS patients with FS antecedents had a statistically significant early
      disease onset (11.5 +/- 8.7 years in FS+ vs. 16.0 +/- 12.1 years in FS-, p <
      0.01). CONCLUSIONS: Our data show that ApoE epsilon4 and FS may not participate
      directly in etiopathogenic mechanisms of MTLE-HS but could hasten the disease
      development in predisposed individuals.

PMID- 27875924
TI  - Explaining ethnic disparities in preterm birth in Argentina and Ecuador.
AB  - Little is understood about racial/ethnic disparities in infant health in South
      America. We quantified the extent to which the disparity in preterm birth (PTB;
      <37 gestational weeks) rate between infants of Native only ancestry and those of
      European only ancestry in Argentina and Ecuador are explained by household socio
      economic, demographic, healthcare use, and geographic location indicators. The
      samples included 5199 infants born between 2000 and 2011 from Argentina and 1579
      infants born between 2001 and 2011 from Ecuador. An Oaxaca-Blinder type
      decomposition model adapted to binary outcomes was estimated to explain the
      disparity in PTB risk across groups of variables and specific variables. Maternal
      use of prenatal care services significantly explained the PTB disparity, by
      nearly 57% and 30% in Argentina and Ecuador, respectively. Household socio
      economic status explained an additional 26% of the PTB disparity in Argentina.
      Differences in maternal use of prenatal care may partly explain ethnic
      disparities in PTB in Argentina and Ecuador. Improving access to prenatal care
      may reduce ethnic disparities in PTB risk in these countries.

PMID- 27875925
TI  - The application of subjective job task analysis techniques in physically
      demanding occupations: evidence for the presence of self-serving bias.
AB  - The aim of this study was to determine if perceptions of physically demanding job
      tasks are biased by employee demographics and employment profile characteristics
      including: age, sex, experience, length of tenure, rank and if they completed or
      supervised a task. Surveys were administered to 427 Royal Australian Navy
      personnel who characterised 33 tasks in terms of physical effort, importance,
      frequency, duration and vertical/horizontal distance travelled. Results showed no
      evidence of bias resulting from participant characteristics, however participants
      who were actively involved in both task participation and supervision rated these
      tasks as more important than those involved only in the supervision of that task.
      This may indicate self-serving bias in which participants that are more actively
      involved in a task had an inflated perception of that task's importance. These
      results have important implications for the conduct of job task analyses,
      especially the use of subjective methodologies in the development of
      scientifically defensible physical employment standards. Practitioner Summary: To
      examine the presence of systematic bias in subjective job task analysis
      methodologies, a survey was conducted on a sample of Royal Australian Navy
      personnel. The relationship between job task descriptions and participant's
      demographic and job profile characteristics revealed the presence of self-serving
      bias affecting perceptions of task importance.

PMID- 27875926
TI  - A meta-analysis of the relationship between symptom severity of Posttraumatic
      Stress Disorder and executive function.
AB  - INTRODUCTION: Some studies of Posttraumatic Stress Disorder (PTSD) find executive
      dysfunction, whereas others do not. We meta-analytically examined the association
      between executive function and PTSD and used meta-regression to examine the
      potential moderating effect of PTSD severity on executive function. METHODS: We
      conducted a meta-analysis according to Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines. We identified published peer-reviewed
      articles containing measures of executive function and PTSD symptom severity in
      subjects with PTSD compared to trauma-unexposed controls or trauma-exposed
      controls without PTSD, or both. We calculated an effect size for each study
      containing at least one measure of executive function and PTSD symptom severity.
      RESULTS: PTSD subjects for whom the Clinician-Administered PTSD Scale (CAPS)
      score was available had worse executive function compared to both trauma
      unexposed controls (g = 0.464, p < .001) and to trauma-exposed controls without
      PTSD (g = 0.414, p = .001), as did PTSD subjects for whom the Mississippi Scale
      for Combat-Related PTSD (M-PTSD) score was available (g = 0.390, p < .001).
      Neither CAPS nor M-PTSD scores significantly moderated the effect size of
      executive function. CONCLUSIONS: PTSD is associated with executive dysfunction,
      but this association was not moderated by PTSD symptom severity, suggesting that
      once PTSD occurs, executive dysfunction may occur regardless of PTSD severity.

PMID- 27875928
TI  - Combining mechanical foaming and thermally induced phase separation to generate
      chitosan scaffolds for soft tissue engineering.
AB  - In this paper, a novel foaming methodology consisting of turbulent mixing and
      thermally induced phase separation (TIPS) was used to generate scaffolds for
      tissue engineering. Air bubbles were mechanically introduced into a chitosan
      solution which forms the continuous polymer/liquid phase in the foam created. The
      air bubbles entrained in the foam act as a template for the macroporous
      architecture of the final scaffolds. Wet foams were crosslinked via
      glutaraldehyde and frozen at -20  degrees C to induce TIPS in order to limit film
      drainage, bubble coalescence and Ostwald ripening. The effects of production
      parameters, including mixing speed, surfactant concentration and chitosan
      concentration, on foaming are explored. Using this method, hydrogel scaffolds
      were successfully produced with up to 80% porosity, average pore sizes of 120 MUm
      and readily tuneable compressive modulus in the range of 2.6 to 25 kPa relevant
      to soft tissue engineering applications. These scaffolds supported 3T3 fibroblast
      cell proliferation and penetration and therefore show significant potential for
      application in soft tissue engineering.

PMID- 27875929
TI  - Introducing a new concept in obstructive sleep apnea: The continuum of treatment.

PMID- 27875930
TI  - Hybrid Aorta Constructs via In Situ Crosslinking of Poly(glycerol-sebacate)
      Elastomer Within a Decellularized Matrix.
AB  - Decellularization of tissues and organs has high potential to obtain unique
      conformation and composition as native tissue structure but may result in
      weakened tissue mechanical strength. In this study, poly(glycerol-sebacate) (PGS)
      elastomers were combined with decellularized aorta fragments to investigate the
      changes in mechanical properties. PGS prepolymer was synthesized via microwave
      irradiation and then in situ crosslinked within the decellularized aorta
      extracellular matrix (ECM). Tensile strength (sigma) values were found comparable
      as 0.44 +/- 0.10 MPa and 0.57 +/- 0.18 MPa for native and hybrid aorta samples,
      respectively, while elongation at break (E) values were 261% +/- 17%, 7.5% +/-
      0.57%, and 22.18% +/- 2.48% for wet control (native), decellularized dried
      aortae, and hybrid matrices, showing elastic contribution. Young's modulus data
      indicate that there was a threefold decrease in stiffness compared to
      decellularized samples once PGS is introduced into the ECM structure. Scanning
      electron microscopy (SEM) analysis of hybrid grafts revealed that the construct
      preserves porosity in medial layer of the vessel. Biocompatibility analyses
      showed no cytotoxic effects on human abdominal aorta smooth muscle cells. Cell
      studies showed 98% activity in hybrid graft extracts. As a control, collagen
      coating of the hybrid grafts was performed in the recellularization stage. SEM
      analysis of recellularized hybrid grafts revealed that cells were attached to the
      surface of the hybrid graft and proliferated during the 14 days of culture in
      both groups. This study shows that introducing an elastomer into the native ECM
      structure following decellularization process can be a useful approach for the
      preparation of mechanically enhanced composites for soft tissues.

PMID- 27875927
TI  - What Is Being Trained? How Divergent Forms of Plasticity Compete To Shape
      Locomotor Recovery after Spinal Cord Injury.
AB  - Spinal cord injury (SCI) is a devastating syndrome that produces dysfunction in
      motor and sensory systems, manifesting as chronic paralysis, sensory changes, and
      pain disorders. The multi-faceted and heterogeneous nature of SCI has made
      effective rehabilitative strategies challenging. Work over the last 40 years has
      aimed to overcome these obstacles by harnessing the intrinsic plasticity of the
      spinal cord to improve functional locomotor recovery. Intensive training after
      SCI facilitates lower extremity function and has shown promise as a tool for
      retraining the spinal cord by engaging innate locomotor circuitry in the lumbar
      cord. As new training paradigms evolve, the importance of appropriate afferent
      input has emerged as a requirement for adaptive plasticity. The integration of
      kinematic, sensory, and loading force information must be closely monitored and
      carefully manipulated to optimize training outcomes. Inappropriate peripheral
      input may produce lasting maladaptive sensory and motor effects, such as central
      pain and spasticity. Thus, it is important to closely consider the type of
      afferent input the injured spinal cord receives. Here we review preclinical and
      clinical input parameters fostering adaptive plasticity, as well as those
      producing maladaptive plasticity that may undermine neurorehabilitative efforts.
      We differentiate between passive (hindlimb unloading [HU], limb immobilization)
      and active (peripheral nociception) forms of aberrant input. Furthermore, we
      discuss the timing of initiating exposure to afferent input after SCI for
      promoting functional locomotor recovery. We conclude by presenting a candidate
      rapid synaptic mechanism for maladaptive plasticity after SCI, offering a
      pharmacological target for restoring the capacity for adaptive spinal plasticity
      in real time.

PMID- 27875932
TI  - Hybrid soliwave technique for mitigating sulfate-reducing bacteria in controlling
      biocorrosion: a case study on crude oil sample.
AB  - Microbiologically influenced corrosion (MIC) is among the common corrosion types
      for buried and deep-water pipelines that result in costly repair and pipeline
      failure. Sulfate-reducing bacteria (SRB) are commonly known as the culprit of
      MIC. The aim of this work is to investigate the performance of combination of
      ultrasound (US) irradiation and ultraviolet (UV) radiation (known as Hybrid
      soliwave technique, HyST) at pilot scale to inactivate SRB. The influence of
      different reaction times with respect to US irradiation and UV radiation and
      synergistic effect toward SRB consortium was tested and discussed. In this
      research, the effect of HyST treatment toward SRB extermination and corrosion
      studies of carbon steel coupon upon SRB activity before and after the treatment
      were performed using weight loss method. The carbon steel coupons immersed in SRB
      sample were exposed to HyST treatment at different time of exposure.
      Additionally, Field Emission Scanning Electron Microscopy coupled with Energy
      Dispersive X-ray Spectroscopy were used to investigate the corrosion morphology
      in verifying the end product of SRB activity and corrosion formation after
      treatment. Results have shown that the US irradiation treatment gives a
      synergistic effect when combined with UV radiation in mitigating the SRB
      consortium.

PMID- 27875933
TI  - Comparison between protein repulsions by diblock PLA-PEO and albumin nanocoatings
      using OWLS.
AB  - A previous investigation suggested that a surface bearing a rinsing-resistant
      depot (nanocoating) of albumin is more protein-repulsive than the same surface
      physically pegylated by a poly(D,L-lactic acid)-poly(ethylene oxide) diblock
      copolymer. To complement the study, Optical Waveguide Lightmode Spectroscopy was
      used to compare the mass and the thickness of protein depots from different
      systems, namely albumin alone at different concentrations, a mixture of albumin +
      fibrinogen + gamma-globulin at their physiological concentrations, and sheep
      serum. The same standard OWLS protocol was applied to compare data for bare
      sensor chips, for chips covered by an albumin nanocoating, and for chips
      physically pegylated using poly(D,L-lactic acid)-poly(ethylene oxide) diblock
      copolymers with different compositions and block lengths. The strategy and the
      conditions being rather different from those generally used to study pegylation
      related antifouling properties; the literature was first reviewed critically.
      Then full coverage of sensor chips by albumin was demonstrated. The comparative
      study confirmed that albumin was more protein-repulsive than any of the diblock
      copolymers, irrespective of the protein system. Furthermore, it was found that
      pegylated surfaces were albumin-repulsive only when the concentration of the
      protein solution flowing over the surface was very low (0.1 g/L). It was not
      possible to correlate the copolymer data to PEO chain density, chain length and
      existence of brush. The in vitro repulsive activity of albumin was not affected
      by drying and rehydration, a feature of interest for storage of albumin-coated
      surfaces. All these observations confirmed our preliminary findings and showed
      that considering model proteins individually or in mixtures at concentrations far
      from physiological concentrations are not suitable to reflect the reality of full
      blood-surface interactions.

PMID- 27875931
TI  - Early numeracy skills in preschool-aged children: a review of neurocognitive
      findings and implications for assessment and intervention.
AB  - OBJECTIVES: The goals are to (1) provide a review of the typical and atypical
      development of early numeracy; (2) present what is known about the neurocognitive
      underpinnings of early numeracy; and (3) discuss the implications for early
      assessment and intervention. METHOD: Studies on the development of typical and
      atypical early numeracy are reviewed with a particular focus on longitudinal
      findings including those from our work on spina bifida myelomeningocele.
      Implications of this research for assessment are presented. The paper ends with a
      discussion of early math interventions. RESULTS: Learning to count, identify
      numbers, and compare and manipulate quantities are key early numeracy skills.
      These are powerful predictors of school-age mathematical learning and
      performance. General neurocognitive abilities such as working memory and
      language, are also important for the development of early numeracy. It is
      recommended that early assessment for risk of mathematical learning difficulties
      include tests of both early number knowledge and key neurocognitive abilities.
      Math-specific interventions are most effective for improving early numeracy.
      There is currently little evidence that training of general cognitive functions
      transfers to mathematical learning. CONCLUSION: Understanding the development of
      early numeracy skills and their neurocognitive predictors offer important
      insights into early assessment and intervention for children at risk for or with
      mathematical learning difficulties.

PMID- 27875934
TI  - Analysis of de novo sequencing and transcriptome assembly and lignocellulolytic
      enzymes gene expression of Coriolopsis gallica HTC.
AB  - White-rot basidiomycete Coriolopsis gallica HTC is one of the main biodegraders
      of poplar. In our previous study, we have shown the strong capacity of C. gallica
      HTC to degrade lignocellulose. In this study, equal amounts of total RNA fromC.
      Gallica HTC cultures grown in different conditions were pooled together. Illumina
      paired-end RNA sequencing was performed, and 13.2 million 90-bp paired-end reads
      were generated. We chose the Merged Assembly of Oases data-set for the following
      blast searches and gene ontology analyses. The reads were assembled de novo into
      28,034 transcripts (>= 100 bp) using combined assembly strategy MAO. The
      transcripts were annotated using Blast2GO. In all, 18,810 transcripts (>=100 bp)
      achieved BLASTX hits, of which, 7048 transcripts had GO term and 2074 had ECs.
      The expression level of 11 lignocellulolytic enzyme genes from the assembled C.
      gallica HTC transcriptome were detected by real-time quantitative polymerase
      chain reaction. The results showed that expression levels of these genes were
      affected by carbon source and nitrogen source at the level of transcription. The
      current abundant transcriptome data allowed the identification of many new
      transcripts in C. gallica HTC. Data provided here represent the most
      comprehensive and integrated genomic resources for cloning and identifying genes
      of interest from C. gallica HTC. Characterization of C. gallica HTC transcriptome
      provides an effective tool to understand mechanisms underlying cellular and
      molecular functions of C. gallica HTC.

PMID- 27875935
TI  - JAK2, MPL, and CALR mutations in Chinese Han patients with essential
      thrombocythemia.
AB  - BACKGROUND: Mutations in Janus kinase 2 (JAK2), myeloproliferative leukemia
      (MPL), and CALR are highly relevant to Philadelphia chromosome (Ph)-negative
      myeloproliferative neoplasms. METHODS: Assessing the prevalence of molecular
      mutations in Chinese Han patients with essential thrombocythemia (ET), and
      correlating their mutational profile with disease characteristics/phenotype.
      RESULTS: Of the 110 subjects studied, 62 carried the JAK2 V617F mutation, 21 had
      CALR mutations, one carried an MPL (W515) mutation, and 28 had non-mutated JAK2,
      CALR, and MPL (so-called triple-negative ET). Mutations in JAK2 exon 12 were not
      detected in any patient. Two ET patients had both CALR and JAK2 V617F mutations.
      Comparing the hematological parameters of the patients with JAK2 mutations with
      those of the patients with CALR mutations showed that the ET patients with CALR
      mutations were younger (p = 0.045) and had higher platelet counts (p = 0.043).
      CONCLUSION: Genotyping for CALR could be a useful diagnostic tool for JAK2/MPL
      negative ET, since the data suggest that CALR is much more prevalent than MPL,
      therefore testing for CALR should be considered in patients who are JAK2 negative
      as its frequency is almost 20 times that of MPL mutation.

PMID- 27875936
TI  - Characterization of dust from blast furnace cast house de-dusting.
AB  - During casting of liquid iron and slag, a considerable amount of dust is emitted
      into the cast house of a blast furnace (BF). Usually, this dust is extracted via
      exhaust hoods and subsequently separated from the ventilation air. In most BFs
      the cast house dust is recycled. In this study a sample of cast house dust was
      split by air classification into five size fractions, which were then analysed.
      Micrographs showed that the dominating particle type in all size fractions is
      that of single spherical-shaped particles. However, some irregular-shaped
      particles were also found and in the finest size fraction also some agglomerates
      were present. Almost spherical particles consisted of Fe and O, while highly
      irregular-shaped particles consisted of C. The most abundant element was Fe,
      followed by Ca and C. These elements were distributed relatively uniformly in the
      size fractions. As, Cd, Cu, K, Pb, S, Sb and Zn were enriched significantly in
      the fine size fractions. Thus, air classification would be an effective method
      for improved recycling. By separating a small fraction of fines (about 10-20%), a
      reduction of the mass of Zn in the coarse dust recycled in the range of 40-55%
      would be possible.

PMID- 27875937
TI  - Operator adaptation to changes in system reliability under adaptable automation.
AB  - This experiment examined how operators coped with a change in system reliability
      between training and testing. Forty participants were trained for 3 h on a
      complex process control simulation modelling six levels of automation (LOA). In
      training, participants either experienced a high- (100%) or low-reliability
      system (50%). The impact of training experience on operator behaviour was
      examined during a 2.5 h testing session, in which participants either experienced
      a high- (100%) or low-reliability system (60%). The results showed that most
      operators did not often switch between LOA. Most chose an LOA that relieved them
      of most tasks but maintained their decision authority. Training experience did
      not have a strong impact on the outcome measures (e.g. performance, complacency).
      Low system reliability led to decreased performance and self-confidence.
      Furthermore, complacency was observed under high system reliability. Overall, the
      findings suggest benefits of adaptable automation because it accommodates
      different operator preferences for LOA. Practitioner Summary: The present
      research shows that operators can adapt to changes in system reliability between
      training and testing sessions. Furthermore, it provides evidence that each
      operator has his/her preferred automation level. Since this preference varies
      strongly between operators, adaptable automation seems to be suitable to
      accommodate these large differences.

PMID- 27875938
TI  - The role of long noncoding RNA HOTAIR in the acquired multidrug resistance to
      imatinib in chronic myeloid leukemia cells.
AB  - OBJECTIVES: Imatinib, a breakpoint cluster region-Abelson murine leukemia
      tyrosine kinase inhibitor, has revolutionized the treatment of chronic
      myelogenous leukemia (CML). However, the development of multidrug resistance
      (MDR) limits the clinical application of imatinib. In this study, we aimed to
      investigate the mechanisms of long noncoding RNA (lncRNA) HOTAIR in CML
      resistance to imatinib. METHODS: Thirty-four CML patients were divided into
      multidrug resistance protein 1 (MRP1)-low and MRP1-high groups according to the
      median expression. Real-time PCR (qPCR) was used to detect the expression of
      lncRNA HOTAIR in CML patients, and MTT assay and flow cytometry assay were
      employed to detect the biological function of silencing lncRNA HOTAIR on the cell
      survival rate and apoptotic rate. An imatinib-resistant human CML cell line K562
      (K562-R) was established, and western blot was used to detect the impact of
      lncRNA HOTAIR on the activation of PI3K/Akt signaling pathway. RESULTS: Our
      results showed that lncRNA HOTAIR was greatly upregulated in the MRP1-high
      patients as well as in the K562-imatinib-resistant cells compared with control.
      Knockdown of HOTAIR expression downregulated the MRP1 expression levels in the
      K562-imatinib cells and resulted in higher sensitivity to the imatinib treatment.
      In addition, the activation of PI3K/Akt was greatly attenuated when HOTAIR was
      knocked down in K562-imatinib cells. DISCUSSIONS: These data suggest that the
      knockdown of HOTAIR may play a crucial role in improving acquired resistance to
      imatinib in CML K562-R cells via PI3K/Akt pathway. CONCLUSIONS: LncRNA HOTAIR
      modulates CML cell MDR in a PI3K/Akt-dependent way.

PMID- 27875939
TI  - Injectable Shape-Memorizing Three-Dimensional Hyaluronic Acid Cryogels for Skin
      Sculpting and Soft Tissue Reconstruction.
AB  - INTRODUCTION: Hyaluronic acid (HA)-based fillers are used for various cosmetic
      procedures. However, due to filler migration and degradation, reinjections of the
      fillers are often required. Methacrylated HA (MA-HA) can be made into injectable
      shape-memorizing fillers (three-dimensional [3D] MA-HA) aimed to address these
      issues. In this study, shape retention, firmness, and biocompatibility of 3D MA
      HA injected subcutaneously in mice were evaluated. MATERIALS AND METHODS: Fifteen
      mice, each receiving two subcutaneous injections in their back, were divided into
      four groups receiving HA, MA-HA, 3D MA-HA, or saline, respectively. Digital
      imaging, scanning electron microscope (SEM) and in vivo imaging system (IVIS),
      durometry, and histology were utilized to evaluate in vitro/vivo degradation and
      migration, material firmness, and the angiogenic (CD31) and immunogenic (CD45)
      response of the host tissue toward the injected materials. RESULTS: Digital
      imaging, SEM, and IVIS revealed that 3D MA-HA fillers maintained their
      predetermined shape for at least 30 days in vitro and in vivo. Little volume
      effects were noted in the saline and other control groups. There were no
      differences in skin firmness between the groups or over time. Histology showed
      intact skin architecture in all groups. Three-dimensional MA-HA maintained its
      macroporous structure with significant angiogenesis at the 3D MA-HA/skin
      interfaces and throughout the 3D MA-HA. There was no significant inflammatory
      response to any of the injected materials. CONCLUSION: 3D MA-HA showed remarkable
      tissue compatibility, compliance, and shape predictability, as well as retention,
      and thus might be suitable for various skin sculpting and soft tissue
      reconstruction purposes.

PMID- 27875940
TI  - Improvement of functionality after chitosan-modified zein biocomposites.
AB  - A series of chitosan-modified zein composite films were fabricated from zein and
      chitosan by a process involving blending, solution casting and evaporation.
      Effects of chitosan content on the structure and physical properties of the
      composite films were investigated by Fourier transform infrared spectroscopy,
      differential scanning calorimetry, scanning electron microscopy, tensile testing,
      water absorption measurement and water contact angle measurement. The results
      showed that the zein/chitosan composite films were fabricated successfully due to
      the formation of hydrogen bonds between zein and chitosan, and the thermal
      stability, water absorption, hydrophilicity, tensile strength, flexibility of the
      composite films increased with an increase in chitosan content from 0 to 50%. The
      cytotoxicity and cytocompatibility of the composite films were evaluated by 3-[45
      dimethyl-2-thiazoly1]-25-diphenyl-2H-tetrazolium bromide (MTT) assay and in vitro
      cell culture, which showed that the films have non- or low-cytotoxicity, and
      chitosan promoted the growth, adhesion and proliferation of the cells. These
      results indicated that chitosan-modified zein composite films might have
      potentials applications as biomaterials.

PMID- 27875941
TI  - Perceived time slows during fleeting fun or fear.
AB  - Previous psychophysical studies at durations greater than 1000 ms have confirmed
      the anecdotal reports of an increase in the perceived duration of both positively
      and negatively valenced emotive stimuli; however, the results of studies at
      durations less than 1000 ms have been inconsistent. This study further
      investigated the effect of valence on the perception of durations less than 1000
      ms. We used both positively and negatively valenced stimuli in order to compare
      their effects on the distortion of duration, and we tested multiple data points
      within the sub-one-second range. We found an increase in the perceived duration
      of both positively and negatively valenced emotional stimuli at all data points.
      This is consistent with studies at durations longer than 1000 ms and also with
      models of temporal processing. We also confirmed that Weber fractions, within the
      range tested, followed the generalized form of Weber's law.

PMID- 27875942
TI  - A combined study of MEG and pico-Tesla TMS on children with autism disorder.
AB  - Magnetoencephalographic (MEG) recordings from the brain of 10 children with
      autism (6 boys and 4 girls, with ages range from 5-12 years, mean[Formula: see
      text][Formula: see text][Formula: see text]SD: 8.3[Formula: see text][Formula:
      see text][Formula: see text]2.1) were obtained using a whole-head 122-channel MEG
      system in a magnetically shielded room of low magnetic noise. A double-blind
      experimental design was used in order to look for possible effect of external
      pico-Tesla Transcranial Magnetic Stimulation (pT-TMS). The pT-TMS was applied on
      the brain of the autistic children with proper field characteristics (magnetic
      field amplitude: 1-7.5[Formula: see text]pT, frequency: the alpha - rhythm of the
      patient 8-13[Formula: see text]Hz). After unblinding it was found a significant
      effect of an increase of frequencies in the range of 2-7[Formula: see text]Hz
      across the subjects followed by an improvement and normalization of their MEG
      recordings. The statistical analysis of our results showed a statistical
      significance at 6 out of 10 patients (60%). It is also observed an increase of
      alpha activity in autistic children at the end of one month after pT-TMS
      treatment at home. In conclusion, the application of pT-TMS has the prospective
      to be a noninvasive, safe and important modality in the management of autism
      children.

PMID- 27875943
TI  - Increasing surfboard volume reduces energy expenditure during paddling.
AB  - The purpose of this study was to investigate how altering surfboard volume (BV)
      affects energy expenditure during paddling. Twenty surfers paddled in a swim
      flume on five surfboards in random order twice. All surfboards varied only in
      thickness and ranged in BV from 28.4 to 37.4 L. Measurements of heart rate (HR),
      oxygen consumption (VO2), pitch angle, roll angle and paddling cadence were
      measured. VO2 and HR significantly decreased on thicker boards [VO2: r = -0.984,
      p = 0.003; HR: r = -0.972, p = 0.006]. There was also a significant decrease in
      pitch and roll angles on thicker boards [Pitch: r = -0.995, p < 0.001; Roll: r = 
      0.911, p = 0.031]. Results from this study suggest that increasing BV reduces the
      metabolic cost of paddling as a result of lower pitch and roll angles, thus
      providing mechanical evidence for increased paddling efficiency on surfboards
      with more volume. Practioner Summary: This study investigated the impact of
      surfboard volume on energy expenditure during paddling. Results from this study
      suggest that increasing surfboard volume reduces the metabolic cost of paddling
      as a result of lower pitch and roll angles, thus providing mechanical evidence
      for increased paddling efficiency on surfboards with more volume.

PMID- 27875944
TI  - Development and evaluation of a novel polymeric hydrogel of sucrose acrylate-co
      polymethylacrylic acid for oral curcumin delivery.
AB  - A monomer of sucrose acrylate (AC-sucrose) was synthesized by conjugating
      starting compound sucrose with methyl acrylate (MA). The obtained AC-sucrose was
      characterized by mass spectrometry (MS) and Fourier transform infrared (FTIR)
      spectroscopy. AC-sucrose was selected as a monomer to fabricate a novel pH
      sensitive hydrogel via free radical polymerization. The inner morphology of the
      final hydrogel was observed with an S-4800 scanning electron microscope (SEM).
      The swelling and de-swelling behaviors of the hydrogel chips were also studied.
      Curcumin (CUR) was selected as a model drug and loaded into the final hydrogel.
      The release profiles of CUR were performed via dialysis method in pH 1.2, 6.8 and
      7.4 buffers, respectively. Mass and FTIR spectra confirmed the synthesis of AC
      sucrose. SEM photographs showed that poly(AC-sucrose-co-MAA) hydrogels had many
      3D meshes. In pH 1.2 buffer, the hydrogel chips showed the biggest swelling ratio
      (SR) of 34.4 +/- 1.9%. However, in pH 7.4 buffer, the SRs of the hydrogel chips
      reached to 368.7 +/- 28.0%, which suggested that the hydrogel had an excellent pH
      sensibility. The releasing profiles showed that only 4.6 +/- 0.4% of CUR was
      released in pH 1.2 buffer but 93.7 +/- 4.7% of CUR was diffused into pH 7.4
      buffer. These data suggested that the CUR-loaded poly (AC-sucrose-co-MAA)
      hydrogel could direct CUR to release in basic environments.

PMID- 27875945
TI  - Three-Dimensional Printing Articular Cartilage: Recapitulating the Complexity of
      Native Tissue<sup/>.
AB  - In the past few decades, the field of tissue engineering combined with rapid
      prototyping (RP) techniques has been successful in creating biological
      substitutes that mimic tissues. Its applications in regenerative medicine have
      drawn efforts in research from various scientific fields, diagnostics, and
      clinical translation to therapies. While some areas of therapeutics are well
      developed, such as skin replacement, many others such as cartilage repair can
      still greatly benefit from tissue engineering and RP due to the low success
      and/or inefficiency of current existing, often surgical treatments. Through
      fabrication of complex scaffolds and development of advanced materials, RP
      provides a new avenue for cartilage repair. Computer-aided design and three
      dimensional (3D) printing allow the fabrication of modeled cartilage scaffolds
      for repair and regeneration of damaged cartilage tissues. Specifically, the
      various processes of 3D printing will be discussed in details, both cellular and
      acellular techniques, covering the different materials, geometries, and
      operational printing conditions for the development of tissue-engineered
      articular cartilage. Finally, we conclude with some insights on future
      applications and challenges related to this technology, especially using 3D
      printing techniques to recapitulate the complexity of native structure for
      advanced cartilage regeneration.

PMID- 27875946
TI  - The Role of Diabetes Mellitus in Sexual and Reproductive Health: An Overview of
      Pathogenesis, Evaluation, and Management.
AB  - BACKGROUND: Uncontrolled or long-term diabetes mellitus is conducive to vascular
      and oxidative stress disturbances that impede several physiological systems,
      which may in turn elicit psychological symptoms. OBJECTIVE: We assess the sexual
      and hormonal complications of diabetes mellitus that impair reproductive function
      in males and females. METHODS: A comprehensive MEDLINE(r) search was guided using
      key words relevant to diabetes mellitus and reproductive health. RESULTS: We
      reviewed the pathogenesis, clinical manifestations, imaging modalities,
      pharmacological treatment, and intervention options for each diabetic
      reproductive complication in males and females. Erectile dysfunction secondary to
      angiopathic, neuropathic, and myopathic damage is a leading complication of
      diabetes in males. Other reproductive complications include ejaculatory
      dysfunction, hypogonadism, modified semen parameters, and delayed puberty.
      Specifics of reproductive dysfunction in diabetic women are less definite than in
      men due to the lack of standardized evaluation of sexual function in women as
      well as the increased role of psychological morbidity. Despite this, it is known
      to manifest as hypogonadism, hypoactive sexual desire disorder, dyspareunia,
      menstrual dysfunction, and polycystic ovarian syndrome. CONCLUSION: Longitudinal
      studies with larger sample sizes are necessary to better comprehend the
      connection between diabetes and sexual dysfunction, chiefly in females.
      Understanding and dividing the role of fertility and sexual issues in
      reproductive dysfunction can help guide evaluation and management.

PMID- 27875947
TI  - Skeletal Muscle Insulin Resistance as a Precursor to Diabetes: Beyond
      Glucoregulation.
AB  - BACKGROUND: Prevalence of Type 2 Diabetes Mellitus (T2DM) has reached pandemic
      levels in the Western societies. T2DM begins with the development of peripheral
      insulin resistance which prior research suggests may commonly originate within
      the skeletal muscle. A number of mechanisms have been proposed for the
      development of muscle insulin resistance including those of classical glucose
      handling, and also other cellular derangements observed in this disease which
      include mitochondrial degeneration, alterations in muscle protein turnover and
      early evidences for dysregulation of the microRNAs. The purpose of the current
      review is to examine the current findings on these latter aspects of
      mitochondrial maintenance, protein turnover and microRNA dysregulation along with
      the potential implications for these derangements in the development of insulin
      resistance and hence T2DM. We summarize multiple evidences for the degeneration
      of mitochondria and known elements of the processes regulating mitochondrial
      quality. Subsequently, we examine current findings of the alterations in muscle
      protein synthesis and autophagic protein degradation in T2DM and potential
      feedback of these systems onto canonical insulin signaling. Finally, evidences
      have emerged for the dysregulation of microRNAs in muscle insulin resistance. Of
      note early data point to several microRNAs altered by the insulin resistant state
      which exhibit relations to classic insulin signaling and the other processes
      discussed here. CONCLUSION: Considering that T2DM may be initiated with muscle
      insulin resistance, improved understanding of the dysregulation of these
      metabolic parameters of skeletal muscle in the pathogenesis of T2DM may be key to
      developing efficacious therapeutic modalities to prevent and treat this
      condition.

PMID- 27875948
TI  - Prevalence, Incidence, Risk and Protective Factors of Amnestic Mild Cognitive
      Impairment in the Elderly in Shanghai.
AB  - BACKGROUND: Amnestic MCI (aMCI) has notably increased in Shanghai, China.
      OBJECTIVE: The study was designed to estimate the prevalence and incidence rates
      of aMCI and to determine the risk and protective factors for aMCI among persons
      >= 60 years-old and >= 70 years-old in Shanghai communities, respectively.
      METHOD: We carried out this 1-year longitudinal study to survey a random sample
      of 1,302 individuals >= 60 years-old, to collect baseline and follow-up data
      about lifestyle through self-reports, and vascular and comorbid conditions from
      medical records and a physical examination. We also analyzed a subgroup of
      individuals >= 70 years-old. RESULTS: The prevalence rate of aMCI in persons >=
      60 years-old was 22.3%, and the incidence rate (per 1,000 person-years) was 96.9.
      Being female was a risk factor for aMCI; protective factors included smoking,
      drinking tea, engaging in intellectual work before retirement, social activities
      and hobbies, regular reading habits, and surfing the internet. The prevalence
      rate of aMCI in persons >= 70 years was 30.3%, and the incidence rate was 145.6.
      Smoking, drinking tea, and surfing the internet were not protective factors for
      this age group (>= 70 years). CONCLUSION: The present study indicates that aMCI
      is a considerable health problem in Shanghai. Preventive strategies for aMCI are
      needed to enhance lifestyle factors that promote brain activity.

PMID- 27875949
TI  - Treponema, Iron and Neurodegeneration.
AB  - Spirochetes are suspected to be linked to the genesis of neurological diseases,
      including neurosyphillis or neurodegeneration (ND). Impaired iron homeostasis has
      been implicated in loss of function in several enzymes requiring iron as a
      cofactor, formation of toxic oxidative species, inflammation and elevated
      production of beta-amyloid proteins. This review proposes to discuss the link
      that may exist between the involvement of Treponema spp. in the genesis or
      worsening of ND, and iron dyshomeostasis. Proteins secreted by Treponema can act
      directly on iron metabolism, with hemin binding ability (HbpA and HbpB) and iron
      reductase able to reduce the central ferric iron of hemin, iron-containing
      proteins (rubredoxin, neelaredoxin, desulfoferrodoxin metalloproteins,
      bacterioferritins etc). Treponema can also interact with cellular compounds,
      especially plasma proteins involved in iron metabolism, contributing to the
      virulence of the syphilis spirochetes (e.g. treponemal motility and survival).
      Fibronectin, transferrin and lactoferrin were also shown to be receptors for
      treponemal adherence to host cells and extracellular matrix. Association between
      Treponema and iron binding proteins results in iron accumulation and
      sequestration by Treponema from host macromolecules during systemic and mucosal
      infections.

PMID- 27875950
TI  - Targeted Delivery of Cabazitaxel by Conjugation to Albumin-PEG-folate
      Nanoparticles Using a Cysteine-acrylate Linker and Simple Synthesis Conditions.
AB  - BACKGROUND: Cabazitaxel (CBZ) is a new taxane approved by FDA for treatment of
      castration- resistant prostate cancer not responding to docetaxel. However, CBZ
      is not a suitable substrate for p-glycoprotein 60, an efflux pump which
      transports anticancer drugs out of malignant cells and is therefore a promising
      drug for treatment of multidrug resistant tumors. Similar to other taxanes, the
      presence of Tween 80 in the CBZ formulation shows that it is insoluble in water.
      METHODS: In order to increase the solubility and circulation time of this drug,
      CBZ-human serum albumin (HSA) conjugate was synthesized. The designed linker was
      composed of methacrylic acid and N-acetyl cysteine to increase the solubility of
      CBZ and to increase the efficiency of conjugation. Targeting was performed by
      poly(ethylene glycol)-folic acid amide bound formation with carboxyl groups of
      HSA during in the step of nanoparticle formation. Cytotoxicity of nanoparticles
      was evaluated in vitro on HT-29, as a folate negative cell line, and MDA-MB-231,
      as a folate positive cell line. RESULTS: H-NMR, Gel Permeation Chromatography,
      High Pressure Liquid Chromatography and UV spectrophotometry analysis confirmed
      the composition of conjugates. The resulting nanoparticles had a spherical shape,
      narrow size distribution and mean diameter of 138 nm. The efficiency of
      conjugation was 41.6 %. The IC50 of CBZ in targeted nanoparticles was 10.1 and
      17.4% lower than that of the free CBZ for HT-29 and MDA-MB-231 cells,
      respectively. CONCLUSION: This designed drug delivery system was more water
      soluble and had enhanced in vitro characteristics and higher cytotoxic activity
      on cancer cells.

PMID- 27875951
TI  - Effect of Administration of Nandrolone Decanoate upon Aldosterone Concentration
      and Serum Na+/K+ Levels in Albino Mice.
AB  - BACKGROUND: This article is a study of adverse effects associated with the abuse
      of recreational drugs such as anabolic androgenic steroids. Nandrolone decanoate
      is one such drug often abused by athletes and bodybuilders seeking enhanced
      physical strength or appearance. The use of such steroids has increased
      dramatically over the years. OBJECTIVE: The present study was conducted to
      investigate the impact of nandrolone decanoate when consumed at an abused dose,
      upon serum aldosterone concentration in albino mice. Sodium and potassium ion
      concentrations were also monitored with the same experimental dosage. METHOD:
      0.1ml of 25 mg Nandrolone decanoate was administered to the animals twice a week
      for a period of 90 days. Blood samples for obtaining the serum from both normal
      and treated group of animals were collected at an interval of 15 days upto the
      90th day. RESULT: The present investigation revealed a significant increase
      (p<0.01) in the serum aldosterone and sodium ion concentrations in the treated
      group of animals compared to that in the normal group. Potassium ion
      concentration in the treated group did not exhibit a significant alteration when
      compared with the untreated animals. CONCLUSION: From the above observation,
      nandrolone decanoate abuse could be suggested as one of the causes of aldosterone
      and electrolyte imbalance in the body that could possibly be a serious risk
      factor for cardiovascular related disorders.

PMID- 27875952
TI  - In Vitro Sensitivity Profiling of Neuroblastoma Cells Against A Comprehensive
      Small Molecule Kinase Inhibitor Library to Identify Agents for Future Therapeutic
      Studies.
AB  - BACKGROUND: Neuroblastoma (NB) constitutes about 8% of all childhood tumors, yet
      accounts for more than 15% of deaths, with an unacceptable overall survival rate.
      These rates are despite the current multimodal therapeutic approaches involving
      surgery, radiation, chemotherapy and myeloablation with hematopoietic stem cell
      rescue. Hence, efforts have intensified to identify new targets and novel
      therapeutic approaches to improve cure rates in these children. Numerous new
      agents for adult malignancies are developed and evaluated for cancer each year,
      providing an invaluable resource, with the added advantage of available
      pharmacologic and toxicity data for consideration. METHODS: To identify potential
      therapeutic targets, we screened a small molecule library of 151 small kinase
      inhibitors against NB cell lines. Based on our initial screening data, we further
      examined the potential of Bcr-Abl targeting small molecule inhibitors to affect
      the growth and survival of NB cells. RESULTS: There is diverse activity among the
      currently available Bcr-Abl inhibitors, possibly reflecting the molecular
      heterogeneity and off-target activity in each combination. In depth analyses of
      ponatinib, an oral multi-target kinase inhibitor and effective agent in the
      treatment of refractory Philadelphia chromosome (Ph) positive leukemia, show
      growth inhibition at sub-micromolar concentrations. In addition, we also
      identified the potential of this agent to interfere with insulin-like growth
      factor-1 receptor (IGF-1R) signaling pathways and Src activity, inhibit cell
      migration and induce apoptosis. CONCLUSION: Our findings provide initial data on
      ponatinib's potential to target key growth regulatory pathways and provide the
      rationale for further studies and evaluation in future early phase clinical
      trials for the treatment of refractory NB.

PMID- 27875953
TI  - Management of Hypertension in Patients with Chronic Kidney Disease in Asia.
AB  - Hypertension is both a cause and consequence of chronic kidney disease (CKD).
      According to the Chinese national survey in 2007-2010, the prevalence of CKD was
      much higher in hypertensive patients (18.9%, n=16,691) than in the overall
      population sample (10.8%, n=47,204). CKD in hypertension confers risks to the
      kidneys as well as other organs. Probably because of high dietary salt intake,
      Asian hypertensive patients with CKD show high prevalence of non-dipping and
      reversed dipping blood pressure pattern, and may have even higher risks of
      cardiovascular disease. Therefore, out-of-office blood pressure evaluation and
      comprehensive cardiovascular evaluations are required. Most of current
      hypertension guidelines recommend intensive antihypertensive treatment in
      hypertensive patients with CKD. This is probably of particular relevance for
      cardiovascular prevention in Asia, because stroke, as a major complication of
      hypertension in Asia, is more closely related to blood pressure than coronary
      events. Intensive blood pressure control to 130/80 mmHg is often required to
      prevent CKD progression and cardiovascular complications. The inhibitors of the
      renin-angiotensin system (RAS) are recommended as the first line antihypertensive
      medications in patients with a glomerular filtration rate higher than 30
      ml/min/1.73 m2, which may more efficaciously prevent end-stage renal disease and
      cardiovascular events. Nonetheless, combination therapy of RAS inhibitors with
      other classes of antihypertensive drugs, such as calcium-channel blockers,
      diuretics, etc, is required to control blood pressure to the target.

PMID- 27875954
TI  - How Immune-inflammatory Processes Link CNS and Psychiatric Disorders:
      Classification and Treatment Implications.
AB  - In this article the emerging biological overlaps of CNS disorders and psychiatric
      conditions are reviewed. Recent work has highlighted how immune-inflammatory
      processes and their interactions with oxidative and nitrosative stress, couple to
      drive changes in neuroregulatory tryptophan catabolites, with consequences for
      serotonin availability, including as a precursor for the melatonergic pathways.
      Subsequent alterations in the regulation of local melatonin synthesis are likely
      to have direct impacts on the reactivity of immune cells, both centrally and
      systemically. These inflammatory processes also lead to the activation of wider
      immune processes. Such wider processes can include the production of
      immunoglobulin (Ig)A and IgM antibody responses, including to tryptophan
      catabolites, emphasizing the importance of immune responses, and their
      interactions with inflammatory processes, in the etiology and course of an array
      of medical conditions, including CNS disorders and psychiatric conditions. Such
      work poses questions as to the validity and utility of current, non-biologically
      based classification systems for psychiatric and CNS disorders. In this article,
      the biological underpinnings of CNS disorders and psychiatric conditions are
      reviewed in the context of how recent data, in reconceptualizing key processes in
      these classically-conceived brain-associated disorders, provides scope for novel,
      and hopefully more clinically useful, treatments. These processes are looked at
      in detail in Alzheimer's disease and major depressive disorder. One important
      treatment target is the gut. Alterations in the gut, including gut permeability
      and the composition of the microbiome, have now become an important target for
      treatment across an array of medical conditions, emphasizing the importance of
      targeting regulators of the immune system in developing novel treatments that are
      based on a more comprehensive and 'wholistic' understanding of currently poorly
      managed medical conditions, particularly psychiatric and CNS disorders.

PMID- 27875955
TI  - Detection of the M. pneumonia in Synovial Fluid of Children with Negative Culture
      Arthritis: A Cross Sectional Study in Tehran, Iran.
AB  - BACKGROUND: Arthritis could be caused by different etiologies ranging from
      rheumatologic diseases to infectious conditions. Therefore, early diagnosis of
      etiology and treatment is important. The purpose of this study was to determine
      the the M. pneumonia in synovial fluid of children with arthritis by 2 methods
      (serology and qualitative PCR). METHODS & MATERIALS: This trial was carried out
      as a cross sectional study in pediatric and orthopedic ward of Rasoul-e Akram
      hospital in Tehran, Iran. Seventy three patients (39 boys and 34 girls) with mean
      age of 11+/- 3.9 y/o were selected by continuous sampling after synovial fluid
      aspiration. All samples were evaluated by direct smear, culture and latex tests.
      Septic arthritis was diagnosed in 18 patients (25.4%). PCR and serology tests for
      M. pneumonia (specific IgM and IgG) were performed in 50 cases with negative
      culture. The results were compared by Independent T test. RESULTS: According to
      physical examination and culture 18 patients (25.4%) were diagnosed with septic
      arthritis, 50 patients with non-septic arthritis were studied. Seventeen patients
      (33.3%) were IgG positive and 2 patients (4%) were IgM positive. Only 2 patients
      (4%) showed weakly positive results on PCR which did not demonstrate any
      association with serology. CONCLUSION: Positive PCR in SF (4%) definitely
      indicates active infection and M. pneumonia induced arthiritis. Although positive
      SF-IgM (4%) suggests either a current or a very recent M. pneumonia infection but
      not for SF-IgG (previous infection). So, we can summate that PCR, though being
      the best and most accurate method to detect M. pneumonia infection arthritis, is
      not considered a practical one due to costs and availability issues. Hence it can
      be safely replaced by serology test (Specific IgM) in SF for diagnosis of M.
      pneumonia arthritis, which is available in most of the hospitals and is much more
      economical as compared to PCR.

PMID- 27875956
TI  - Editorial : Combined use of Computed Chemodescriptors and Biodescriptors in the
      Evaluation of Chemicals for New Drug Discovery and Environmental Protection: A
      Pragmatic Approach.

PMID- 27875957
TI  - Editorial.

PMID- 27875958
TI  - Commentary: Death Associated Protein Kinase 1: A Perp in Cerebral Ischemia.

PMID- 27875959
TI  - Editorial (Thematic Issue: Molecular and Cellular Engineering Approaches for
      Neurological Disorders, Diseases, and Injuries Involved the Central and
      Peripheral Nervous Systems).

PMID- 27875960
TI  - Neuroprotective Effects of an Erythropoietin-Derived Peptide in PC1 2 Cells under
      Oxidative Stress.
AB  - Erythropoietin (EPO) has been shown to be a key cytokine in the production of
      erythrocytes from erythroblasts. Recently, attempts have been made to adopt EPO
      as a drug target for neuroprotection in selected neurological pathologies. In the
      current study, a novel EPO-derived peptide which mimics the weak binding site of
      EPO to its receptor (MK-X) was generated. Experimental results demonstrated that
      MK-X was able to ameliorate neuronal death due to reactive oxygen species and
      conditions of oxidative stress similar to EPO. In addition, MK-X induced long
      lasting Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Akt
      activation. Furthermore, treatment with inhibitors of ERK1/2 and Akt abolished
      the neuroprotective effect of MK-X. Unlike EPO, however, MK-X did not induce
      cellular proliferation. Collectively, the results of the current study suggested
      that MK-X may be useful as a novel neuroprotective reagent.

PMID- 27875961
TI  - Editorial (Thematic Issue: From Old Cannabinoids to Emerging New Synthetic
      Derivatives with Potential Therapeutic Application in Neurological Disorders).

PMID- 27875963
TI  - Engineering Virus-like Particles for Antigen and Drug Delivery.
AB  - Virus-like particles (VLPs) are nanoscale biological structures consisting of
      viral proteins assembled in a morphology that mimic the native virion but do not
      contain the viral genetic material. The possibility of chemically and genetically
      modifying the proteins contained within VLPs makes them an attractive system for
      numerous applications. As viruses are potent immune activators as well as natural
      delivery vehicles of genetic materials to their host cells, VLPs are especially
      well suited for antigen and drug delivery applications. Despite the great
      potential, very few VLP designs have made it through clinical trials. In this
      review, we will discuss the challenges of developing VLPs for antigen and drug
      delivery, strategies being explored to address these challenges, and the genetic
      and chemical approaches available for VLP engineering.

PMID- 27875964
TI  - Bioengineering for Microbial Inulinases: Trends and Applications.
AB  - Inulinase has attracted attention due to their number of applications in various
      industries viz. pharmaceuticals, food and bioethanol. Enzymes due to their unique
      properties and enormous power of catalysis at very wide range of temperature are
      always in demand in industries. There are certain techniques which are employed
      to improve the productivity of enzymes as well as enhancing their catalytic
      activity. Modeling of structure of inulinase will provide an overview of the
      catalytic domain and help in improvising catalytic potential. In the present
      review we have discussed on the topics of different substrate specificity and
      statistical optimization methods for the improvement of inulinase production.
      Recovery of enzyme is a cost effective approach and crucial step in the
      industrial application of enzyme and can be achieved by different immobilizing
      techniques. Immobilized inulinases have been widely studied and applied in
      different bioreactor systems. Kluyveromyces, Aspergillus, Staphylococcus,
      Xanthomonas, and Pseudomonas are few high level of inulinase producing
      microorganisms and are commercially employed for production of certain important
      product. Since inulins are used as prebiotic, it has also great impact in the
      nutritional biology field. Inulinase in food industries and inulin as probiotic
      are also discussed.

PMID- 27875962
TI  - The Beneficial Effects of Taurine to Counteract Sarcopenia.
AB  - Aging is a multifactorial process characterized by several features including low
      grade inflammation, increased oxidative stress and reduced regenerative capacity,
      which ultimately lead to alteration in morpho-functional properties of skeletal
      muscle, thus promoting sarcopenia. This condition is characterized by a gradual
      loss of muscle mass due to an unbalance between protein synthesis and
      degradation, finally conveying in functional decline and disability. The
      development of specific therapeutic approaches able to block or reverse this
      condition may represent an invaluable tool for the promotion of a healthy aging
      among elderly people. It is well established that changes in the quantity and the
      quality of dietary proteins, as well as the intake of specific amino acids, are
      able to counteract some of the physiopathological processes related to the
      progression of the loss of muscle mass and may have beneficial effects in
      improving the anabolic response of muscle in the elderly. Taurine is a non
      essential amino acid expressed in high concentration in several mammalian tissues
      and particularly in skeletal muscle where it is involved in the modulation of
      intracellular calcium concentration and ion channel regulation and where it also
      acts as an antioxidant and anti-inflammatory factor. The aim of this review is to
      summarize the pleiotropic effects of taurine on specific muscle targets and to
      discuss its role in regulating signaling pathways involved in the maintenance of
      muscle homeostasis. We also highlight the potential use of taurine as a
      therapeutic molecule for the amelioration of skeletal muscle function and
      performance severely compromised during aging.

PMID- 27875965
TI  - Stimulation of Laccase Biocatalysis in Ionic Liquids: A Review on Recent
      Progress.
AB  - It has been well known that laccases can directly or indirectly catalyze
      oxidation of a broad species of phenols, amines and many other electron donor
      substrates. However, laccases as biocatalyst in "green" ionic liquids (ILs) media
      instead of conventional solvents are less known and regarded as an innovative
      research direction. The presence of ILs can either inhibit or stimulate laccase
      activity, strongly depending on water-miscibility and kosmotropic natures of ILs.
      In addition, enzyme source, mediator, pH as well as water content are very
      important factors which influence laccase activity and stability. Therefore,
      elucidation of mechanisms underlying the interactions between laccases and ILs
      will facilitate to screen ILs with excellent laccase compatibility. Strategies
      based on molecular evolution, enzyme immobilization and/or ILs modification
      greatly increase the tolerance of laccases against specific ILs. The use of ILs
      can spread the laccase applications in fields of biosynthesis, biodegradation,
      biosensor and biofuel cells. This article summarizes the recent progress, trends
      and problems in this field and focuses, in particular, on the stimulation of
      laccase activity in aqueous ILs media.

PMID- 27875967
TI  - Microbial P450 Enzymes in Bioremediation and Drug Discovery: Emerging Potentials
      and Challenges.
AB  - Cytochrome P450 enzymes are a structurally conserved but functionally diverse
      group of heme-containing mixed function oxidases found across both prokaryotic
      and eukaryotic forms of the microbial world. Microbial P450s are known to perform
      diverse functions ranging from the synthesis of cell wall components to
      xenobiotic/drug metabolism to biodegradation of environmental chemicals.
      Conventionally, many microbial systems have been reported to mimic mammalian P450
      like activation of drugs and were proposed as the in-vitro models of mammalian
      drug metabolism. Recent reports suggest that native or engineered forms of
      specific microbial P450s from these and other microbial systems could be employed
      for desired specific biotransformation reactions toward natural and synthetic
      (drug) compounds underscoring their emerging potential in drug improvement and
      discovery. On the other hand, microorganisms particularly fungi and actinomycetes
      have been shown to possess catabolic P450s with unusual potential to degrade
      toxic environmental chemicals including persistent organic pollutants (POPs).
      Wood-rotting basidiomycete fungi in particular have revealed the presence of
      exceptionally large P450 repertoire (P450ome) in their genomes, majority of which
      are however orphan (with no known function). Our pre- and post-genomic studies
      have led to functional characterization of several fungal P450s inducible in
      response to exposure to several environmental toxicants and demonstration of
      their potential in bioremediation of these chemicals. This review is an attempt
      to summarize the postgenomic unveiling of this versatile enzyme superfamily in
      microbial systems and investigation of their potential to synthesize new drugs
      and degrade persistent pollutants, among other biotechnological applications.

PMID- 27875966
TI  - Recombinant Approaches for Microbial Xylanases: Recent Advances and Perspectives.
AB  - Xylanases are crucial enzymes to hydrolyse the xylan of plant hemicellulose in
      order to complete the carbon cycle. Xylanases have been used widely in a variety
      of industries ranging from food and feed industry to pulp and paper industry.
      Most of the industrial processes which using xylanase requires a thermostable and
      alkali stable enzyme. Therefore it is desired to produce high thermostable and
      alkali stable xylanase with high activity. In this review a number of molecular
      techniques are used in this genomic era have been utilized to enhance
      physiological properties of xylanases for greater commercial application in the
      industries. A brief outline of diverse molecular techniques such as genome
      walking PCR, thermal asymmetric interlaced PCR (TAIL-PCR), staggered extension
      process (StEP) recombination method, site-directed mutagenesis together with
      metagenomic approaches have been discussed which are used to improve the
      charactestics of xylanases and its production. Metagenomic studies along with
      directed evolution by mutant creation have also been reported as an effective
      tool in improvement of xylanase activity and its properties. This review
      comprehensively describes the recent reports and different combinatorial
      approaches towards production of efficient xylanases.

PMID- 27875968
TI  - Re-engineering of Bacterial Luciferase; For New Aspects of Bioluminescence.
AB  - Bacterial luminescence is the end-product of biochemical reactions catalyzed by
      the luciferase enzyme. Nowadays, this fascinating phenomenon has been widely used
      as reporter and/or sensors to detect a variety of biological and environmental
      processes. The enhancement or diversification of the luciferase activities will
      increase the versatility of bacterial luminescence. Here, to establish the
      strategy for luciferase engineering, we summarized the identity and relevant
      roles of key amino acid residues modulating luciferase in Vibrio harveyi, a model
      luminous bacterium. The current opinions on crystal structures and the critical
      amino acid residues involved in the substrate binding sites and unstructured loop
      have been delineated. Based on these, the potential target residues and/or
      parameters for enzyme engineering were also suggested in limited scale. In
      conclusion, even though the accurate knowledge on the bacterial luciferase is yet
      to be reported, the structure-guided site-directed mutagenesis approaches
      targeting the regulatory amino acids will provide a useful platform to re
      engineer the bacterial luciferase in the future.

PMID- 27875969
TI  - Microbial Interactions in Plants: Perspectives and Applications of Proteomics.
AB  - The structure and function of proteins involved in plant-microbe interactions is
      investigated through large-scale proteomics technology in a complex biological
      sample. Since the whole genome sequences are now available for several plant
      species and microbes, proteomics study has become easier, accurate and huge
      amount of data can be generated and analyzed during plant-microbe interactions.
      Proteomics approaches are highly important and relevant in many studies and
      showed that only genomics approaches are not sufficient enough as much
      significant information are lost as the proteins and not the genes coding them
      are final product that is responsible for the observed phenotype. Novel
      approaches in proteomics are developing continuously enabling the study of the
      various aspects in arrangements and configuration of proteins and its functions.
      Its application is becoming more common and frequently used in plant-microbe
      interactions with the advancement in new technologies. They are more used for the
      portrayal of cell and extracellular destructiveness and pathogenicity variables
      delivered by pathogens. This distinguishes the protein level adjustments in host
      plants when infected with pathogens and advantageous partners. This review
      provides a brief overview of different proteomics technology which is currently
      available followed by their exploitation to study the plant-microbe interaction.

PMID- 27875970
TI  - A Systematic Prediction of Drug-Target Interactions Using Molecular Fingerprints
      and Protein Sequences.
AB  - BACKGROUND: Drug-Target Interactions (DTI) play a crucial role in discovering new
      drug candidates and finding new proteins to target for drug development. Although
      the number of detected DTI obtained by high-throughput techniques has been
      increasing, the number of known DTI is still limited. On the other hand, the
      experimental methods for detecting the interactions among drugs and proteins are
      costly and inefficient. OBJECTIVE: Therefore, computational approaches for
      predicting DTI are drawing increasing attention in recent years. In this paper,
      we report a novel computational model for predicting the DTI using extremely
      randomized trees model and protein amino acids information. METHOD: More
      specifically, the protein sequence is represented as a Pseudo Substitution Matrix
      Representation (Pseudo-SMR) descriptor in which the influence of biological
      evolutionary information is retained. For the representation of drug molecules, a
      novel fingerprint feature vector is utilized to describe its substructure
      information. Then the DTI pair is characterized by concatenating the two vector
      spaces of protein sequence and drug substructure. Finally, the proposed method is
      explored for predicting the DTI on four benchmark datasets: Enzyme, Ion Channel,
      GPCRs and Nuclear Receptor. RESULTS: The experimental results demonstrate that
      this method achieves promising prediction accuracies of 89.85%, 87.87%, 82.99%
      and 81.67%, respectively. For further evaluation, we compared the performance of
      Extremely Randomized Trees model with that of the state-of-the-art Support Vector
      Machine classifier. And we also compared the proposed model with existing
      computational models, and confirmed 15 potential drug-target interactions by
      looking for existing databases. CONCLUSION: The experiment results show that the
      proposed method is feasible and promising for predicting drug-target interactions
      for new drug candidate screening based on sizeable features.

PMID- 27875971
TI  - Therapeutic Suppression of Nonsense Mutation: An Emerging Target in Multiple
      Diseases and Thrombotic Disorders.
AB  - Nonsense mutations contribute to approximately 10-30% of the total human
      inherited diseases via disruption of protein translation. If any of the three
      termination codons (UGA, UAG and UAA) emerges prematurely [known as premature
      termination codon (PTC)] before the natural canonical stop codon, truncated
      nonfunctional proteins or proteins with deleterious loss or gain-of-function
      activities are synthesized, followed by the development of nonsense mutation
      mediated diseases. In the past decade, PTC-associated diseases captured much
      attention in biomedical research, especially as molecular therapeutic targets via
      nonsense suppression (i.e. translational readthrough) regimens. In this review,
      we highlighted different treatment strategies of PTC targeting readthrough
      therapeutics including the use of aminoglycosides, ataluren (formerly known as
      PTC124), suppressor tRNAs, nonsense-mediated mRNA decay, pseudouridylation and
      CRISPR/Cas9 system to treat PTC-mediated diseases. In addition, as thrombotic
      disorders are a group of disease with major burdens worldwide, 19 potential genes
      containing a total of 705 PTCs that cause 21 thrombotic disorders have been
      listed based on the data reanalysis from the 'GeneCards(r) - Human Gene Database'
      and 'Human Gene Mutation Database' (HGMD(r)). These PTC-containing genes can be
      potential targets amenable for different readthrough therapeutic strategies in
      the future.

PMID- 27875972
TI  - The Role of Chinese Herbal Medicines and Bioactive Ingredients Targeting
      Myocardial KCa and KATP Channels in Cardiovascular Diseases.
AB  - Cardiovascular disorders are the most common diseases all over the world, which
      have limitations in the current treatment stratergies. As two subtypes of
      potassium channel, KCa and KATP ion channels are playing important roles in the
      occurrence and development of cardiovascular diseases. KCa by activating the
      signal pathway of c-Src/PI3-kinase/Akt-dependent or eNOS-NO-cGMP effects the
      function of vascular endothelial cell, while KATP acting as a medium combines the
      cell electrical activity and energy metabolism. Thus, through acting on KCa
      or/and KATP, some drugs can play roles in these cardiovascular diseases.
      Nevertheless, specific and effective western medicines selectively working on
      these two channels are not identified at present. Some Chinese herbal medicines
      or bioactive ingredients in contrast have been discovered to be safe and
      effective in the regulation of the two recently. Therefore, this review article
      summarized some single herbs and bioactive ingredients targeting KCa or/and KATP
      ion channels in the management of cardiovascular diseases, with the purpose of
      demonstrating the alternative treatment of these diseases in perspective of
      Traditional Chinese medicine.

PMID- 27875973
TI  - Structural Modifications of Diarylpyrimidine-quinolone Hybrids as Potent HIV-1
      NNRTIs with an Improved Drug Resistance Profile.
AB  - Earlier we reported the identification of diarylpyrimidine-quinolone hybrids as a
      new class of HIV-1 NNRTIs. A few of these hybrids displayed moderate inhibitory
      activity against wt HIV-1 replication at submicromolar level, however, all of
      them lacked inhibitory activity against the double mutant virus (K103N/Y181C),
      which is the most prevalent NNRTI resistant-associated double mutant observed in
      the clinic. In the present study, we designed and synthesized a new series of
      diarylpyrimidine-quinolone hybrids featuring a halogen group at C-6' position of
      quinolone ring. The biological results indicated that most of these hybrids could
      inhibit wt HIV-1 replication at nanomolar level ranging from 0.088 to 0.0096 MUM.
      The most promising hybrid 5c displayed a significant EC50 value of 0.0096 MUM
      against HIV-1 IIIB and of 0.98 MUM against K103N/Y181C. Further docking studies
      revealed that these hybrids could be well located in the hydrophobic NNIBP of HIV
      1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid
      scaffold in the molecules. These promising results suggested a high potential to
      further develop these hybrids as next-generation NNRTIs with improved antiviral
      efficacy and resistance profile.

PMID- 27875974
TI  - Nanoparticle Systems Modulating Myeloid-Derived Suppressor Cells for Cancer
      Immunotherapy.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of
      immature myeloid cells that are preferentially expanded in cancer. They arise
      from myeloid progenitor cells that do not differentiate into mature dendritic
      cells (DCs), granulocytes, or macrophages, and are rather thought to play a
      pivotal role in immune escape and cancer progression. MDSCs are characterized by
      the ability to suppress T cell proliferation and cytotoxicity, inhibit natural
      killer T (NKT) cell activation, and induce the differentiation and expansion of
      regulatory T cells (Treg). MDSC levels have been shown to correlate negatively
      with prognosis and overall survival of patients with cancers of various types and
      stages. The role of MDSCs in cancer progression represents a promising target for
      effective cancer immunotherapy. In this review, we discuss the mechanisms of MDSC
      functions, their influence on tumor progression and metastasis, and finally focus
      on up to date nanoparticle approaches that target and antagonize MDSCs in tumor
      bearing hosts. The development of multifunctional nanoparticle systems for
      effective imaging, assessment and manipulation of MDSCs will represent strategic
      theranostic innovations that may improve cancer staging, therapeutic outcomes,
      and overall patient survival.

PMID- 27875975
TI  - Self-assembly of DNA-based Nanomaterials and Potential Application in Drug
      Delivery.
AB  - DNA can be self-assembled into programmable two-dimensional and three-dimensional
      nanoarchitectures with arbitrarily predetermined sizes and shapes. Because of the
      addressable arbitrary size and shape, great capacity of cargo loading, ability to
      be internalized by cells, the stability of structures under physiological
      conditions and excellent biocompatibility, the pristine DNA nanostructures are
      explored as drug vehicles in drug delivery. In addition, DNA block copolymer and
      DNADendron hybrid, as new building blocks, can be self-assembled into different
      kinds of ordered structures, e.g., nanofibers, spherical micelles, and vesicles,
      in aqueous solution. Recent studies have shown that some of these nanostructures
      could easily enter cells with excellent cell uptake efficiency. Herein, this
      review will mainly introduce the self-assembly behavior of pristine DNA and DNA
      hybrid materials including DNA block copolymers and DNA-Dendron hybrids, and
      their application in drug delivery.

PMID- 27875976
TI  - Micro-/Nano-Scale Biointerfaces, Mechanical Coupling and Cancer Therapy.
AB  - The interaction between cancer cells and their microenvironment is an
      indispensable link in cancer progression that occurs on the interfaces between
      them and presents typical biointerfacial behavior. Recently, the cancer
      cell/microenvironment interface has begun to attract more attention because of
      its fundamental roles in cancer growth and metastasis, which is promising for the
      efficacy of anti-cancer drugs and other important effects. In this review, we
      focused on mechanical coupling of the biointerfaces and their application in
      cancer early diagnosis, the pharmacology of anticancer agents and the design of
      the anticancer drug carriers. Newly developed strategies for cancer therapy based
      on mechanical coupling, such as correcting cell mechanics defects, tunable
      rigidity for drug delivery and topography-coupled-mechanical drug design, and
      drug screening, provide a proof of concept that cell mechanics offer a rich drug
      target space, allowing for the possible corrective modulation of tumor cell
      behavior. Biomechanopharmacology is therefore important to recognize the
      biomechanical factors and to control them not only for improvement in our
      knowledge of cancer but also for the development of new drugs and new uses of old
      drugs.

PMID- 27875977
TI  - Theranostics Based on Iron Oxide and Gold Nanoparticles for Imaging- Guided
      Photothermal and Photodynamic Therapy of Cancer.
AB  - With the progress of nanotechnology, the treatment of cancer by photothermal
      therapy (PTT) and photodynamic therapy (PDT) using theranostic nanomaterials
      based on iron oxide (Fe3O4) and gold (Au) nanoparticles (NPs) has received much
      attention in recent years. The Fe3O4 NPs have been used as imaging-guided PTT of
      cancer due to their high relaxivity, excellent contrast enhancement, and less
      toxicity. The Au NPs have been widely employed as a contrast agent for CT imaging
      of different biological systems due to their enhanced X-ray attenuation property.
      Due to the strong surface plasmon resonance (SPR) absorption intensity in near
      infrared (NIR) region, Au NPs have been considered for imaging-guided PTT of
      cancer. Since the photosensitizer, which plays an important role in PDT of
      cancer, can be efficiently conjugated with Fe3O4 and Au NPs, these NPs have also
      been considered for imaging-guided PDT of cancer. It has been found that both
      Fe3O4 and Au NPs allow passive targeting of tumors through enhanced permeability
      and retention (EPR) effect to improve the treatment efficacy in PTT and PDT. The
      present review focuses on the recent developments of Fe3O4 and Au-based NPs as
      theranostics for imaging-guided PTT and PDT of cancer.

PMID- 27875978
TI  - Near-infrared Light Responsive Polymeric Nanocomposites for Cancer Therapy.
AB  - Inorganic nanoparticles, which can absorb and convert near infrared (NIR) light
      to heat to ablate cancer cells, have been widely investigated in photothermal
      therapy. However, the inherent poor solubility and acute systemic toxicity of
      these inorganic particles hinder their application in clinical practice.
      Polymeric nanocomposites materials containing both inorganic nanoparticles and
      polymers could be harnessed to achieve enhanced photothermal therapeutic effect
      as well as improved biocompatibility and multi-responsiveness. Synergistic chemo
      photothermal efficacy towards cancer cells and tumor tissue can thus be realized
      through such multi-functional and multi-responsive polymeric nanocomposites. In
      this review, the recent developments in polymeric nanocomposites based on
      different types of inorganic nanoparticles (i.e. gold, carbon nanotube, graphene,
      and upconversion nanoparticles) for NIR-triggered cancer therapy are summarized.

PMID- 27875979
TI  - Self-assembled Nucleic Acid Nanostructures for Cancer Theranostic Medicines.
AB  - Theranostic medicine has become more promising in cancer treatment, where the
      cancer diagnosis and chemotherapy are combined for early diagnosis and precise
      treatment with improved efficacy and reduced side effects. Nanotechnology has
      played a critical role in developing various nanomaterials with engendered smart
      functions and targeted delivery. The rapid development of structural DNA
      nanotechnology has enabled the design and fabrication of complex nanostructures
      with prescribed 1D, 2D and 3D patterns in vitro and in vivo. Self-assembled DNA
      nanostructures can serve as drug delivery platforms that are integrated with
      various functions ranging from molecular recognition and computations,
      dynamically structural switch to carrying molecular payloads and selectively
      release. In this review, we summarize recent exciting progress of using DNA
      nanostructures to engineer novel smart drug-delivery systems potential for
      treating cancer.

PMID- 27875981
TI  - A statistical model for the analysis of beta values in DNA methylation studies.
AB  - BACKGROUND: The analysis of DNA methylation is a key component in the development
      of personalized treatment approaches. A common way to measure DNA methylation is
      the calculation of beta values, which are bounded variables of the form M/(M+U)
      that are generated by Illumina's 450k BeadChip array. The statistical analysis of
      beta values is considered to be challenging, as traditional methods for the
      analysis of bounded variables, such as M-value regression and beta regression,
      are based on regularity assumptions that are often too strong to adequately
      describe the distribution of beta values. RESULTS: We develop a statistical model
      for the analysis of beta values that is derived from a bivariate gamma
      distribution for the signal intensities M and U. By allowing for possible
      correlations between M and U, the proposed model explicitly takes into account
      the data-generating process underlying the calculation of beta values. Using
      simulated data and a real sample of DNA methylation data from the Heinz Nixdorf
      Recall cohort study, we demonstrate that the proposed model fits our data
      significantly better than beta regression and M-value regression. CONCLUSION: The
      proposed model contributes to an improved identification of associations between
      beta values and covariates such as clinical variables and lifestyle factors in
      epigenome-wide association studies. It is as easy to apply to a sample of beta
      values as beta regression and M-value regression.

PMID- 27875980
TI  - Comparative genomics of European avian pathogenic E. Coli (APEC).
AB  - BACKGROUND: Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which
      results in significant economic losses to the poultry industry worldwide.
      However, the diversity between isolates remains poorly understood. Here, a total
      of 272 APEC isolates collected from the United Kingdom (UK), Italy and Germany
      were characterised using multiplex polymerase chain reactions (PCRs) targeting 22
      equally weighted factors covering virulence genes, R-type and phylogroup.
      Following these analysis, 95 of the selected strains were further analysed using
      Whole Genome Sequencing (WGS). RESULTS: The most prevalent phylogroups were B2
      (47%) and A1 (22%), although there were national differences with Germany
      presenting group B2 (35.3%), Italy presenting group A1 (53.3%) and UK presenting
      group B2 (56.1%) as the most prevalent. R-type R1 was the most frequent type
      (55%) among APEC, but multiple R-types were also frequent (26.8%). Following
      compilation of all the PCR data which covered a total of 15 virulence genes, it
      was possible to build a similarity tree using each PCR result unweighted to
      produce 9 distinct groups. The average number of virulence genes was 6-8 per
      isolate, but no positive association was found between phylogroup and number or
      type of virulence genes. A total of 95 isolates representing each of these 9
      groupings were genome sequenced and analysed for in silico serotype, Multilocus
      Sequence Typing (MLST), and antimicrobial resistance (AMR). The UK isolates
      showed the greatest variability in terms of serotype and MLST compared with
      German and Italian isolates, whereas the lowest prevalence of AMR was found for
      German isolates. Similarity trees were compiled using sequencing data and notably
      single nucleotide polymorphism data generated ten distinct geno-groups. The
      frequency of geno-groups across Europe comprised 26.3% belonging to Group 8
      representing serogroups O2, O4, O18 and MLST types ST95, ST140, ST141, ST428,
      ST1618 and others, 18.9% belonging to Group 1 (serogroups O78 and MLST types
      ST23, ST2230), 15.8% belonging to Group 10 (serogroups O8, O45, O91, O125ab and
      variable MLST types), 14.7% belonging to Group 7 (serogroups O4, O24, O35, O53,
      O161 and MLST type ST117) and 13.7% belonging to Group 9 (serogroups O1, O16,
      O181 and others and MLST types ST10, ST48 and others). The other groups (2, 3, 4,
      5 and 6) each contained relatively few strains. However, for some of the
      genogroups (e.g. groups 6 and 7) partial overlap with SNPs grouping and PCR
      grouping (matching PCR groups 8 (13 isolates on 22) and 1 (14 isolates on 16)
      were observable). However, it was not possible to obtain a clear correlation
      between genogroups and unweighted PCR groupings. This may be due to the genome
      plasticity of E. coli that enables strains to carry the same virulence factors
      even if the overall genotype is substantially different. CONCLUSIONS: The
      conclusion to be drawn from the lack of correlations is that firstly, APEC are
      very diverse and secondly, it is not possible to rely on any one or more basic
      molecular or phenotypic tests to define APEC with clarity, reaffirming the need
      for whole genome analysis approaches which we describe here. This study
      highlights the presence of previously unreported serotypes and MLSTs for APEC in
      Europe. Moreover, it is a first step on a cautious reconsideration of the merits
      of classical identification criteria such as R typing, phylogrouping and
      serotyping.

PMID- 27875983
TI  - Liver transcriptome response to hyperthermic stress in three distinct chicken
      lines.
AB  - BACKGROUND: High ambient temperatures cause stress in poultry, especially for
      broiler lines, which are genetically selected for rapid muscle growth. RNA-seq
      technology provides powerful insights into environmental response from a highly
      metabolic tissue, the liver. We investigated the effects of acute (3 h, 35 
      degrees C) and chronic (7d of 35  degrees C for 7 h/d) heat stress on the liver
      transcriptome of 3-week-old chicks of a heat-susceptible broiler line, a heat
      resistant Fayoumi line, and their advanced intercross line (AIL). RESULTS:
      Transcriptome sequencing of 48 male chickens using Illumina HiSeq 2500 technology
      yielded an average of 33.9 million, 100 base-pair, single-end reads per sample.
      There were 8 times more differentially expressed genes (DEGs) (FDR < 0.05) in
      broilers (n = 627) than Fayoumis (n = 78) when comparing the acute-heat samples
      to the control (25  degrees C) samples. Contrasting genetic lines under similar
      heat treatments, the highest number of DEGs appeared between Fayoumi and broiler
      lines. Principal component analysis of gene expression and analysis of the number
      of DEGs suggested that the AIL had a transcriptomic response more similar to the
      Fayoumi than the broiler line during acute heat stress. The number of DEGs also
      suggested that acute heat stress had greater impact on the broiler liver
      transcriptome than chronic heat stress. The angiopoietin-like 4 (ANGPTL4) gene
      was identified as differentially expressed among all 6 contrasts. Ingenuity
      Pathway Analysis (IPA) created a novel network that combines the heat shock
      protein family with immune response genes. CONCLUSIONS: This study extends our
      understanding of the liver transcriptome response to different heat exposure
      treatments in distinct genetic chicken lines and provides information necessary
      for breeding birds to be more resilient to the negative impacts of heat. The data
      strongly suggest ANGPTL4 as a candidate gene for improvement of heat tolerance in
      chickens.

PMID- 27875982
TI  - Comparative genomics to explore phylogenetic relationship, cryptic sexual
      potential and host specificity of Rhynchosporium species on grasses.
AB  - BACKGROUND: The Rhynchosporium species complex consists of hemibiotrophic fungal
      pathogens specialized to different sweet grass species including the cereal crops
      barley and rye. A sexual stage has not been described, but several lines of
      evidence suggest the occurrence of sexual reproduction. Therefore, a comparative
      genomics approach was carried out to disclose the evolutionary relationship of
      the species and to identify genes demonstrating the potential for a sexual cycle.
      Furthermore, due to the evolutionary very young age of the five species currently
      known, this genus appears to be well-suited to address the question at the
      molecular level of how pathogenic fungi adapt to their hosts. RESULTS: The
      genomes of the different Rhynchosporium species were sequenced, assembled and
      annotated using ab initio gene predictors trained on several fungal genomes as
      well as on Rhynchosporium expressed sequence tags. Structures of the rDNA regions
      and genome-wide single nucleotide polymorphisms provided a hypothesis for intra
      genus evolution. Homology screening detected core meiotic genes along with most
      genes crucial for sexual recombination in ascomycete fungi. In addition, a large
      number of cell wall-degrading enzymes that is characteristic for hemibiotrophic
      and necrotrophic fungi infecting monocotyledonous hosts were found. Furthermore,
      the Rhynchosporium genomes carry a repertoire of genes coding for polyketide
      synthases and non-ribosomal peptide synthetases. Several of these genes are
      missing from the genome of the closest sequenced relative, the poplar pathogen
      Marssonina brunnea, and are possibly involved in adaptation to the grass hosts.
      Most importantly, six species-specific genes coding for protein effectors were
      identified in R. commune. Their deletion yielded mutants that grew more
      vigorously in planta than the wild type. CONCLUSION: Both cryptic sexuality and
      secondary metabolites may have contributed to host adaptation. Most importantly,
      however, the growth-retarding activity of the species-specific effectors suggests
      that host adaptation of R. commune aims at extending the biotrophic stage at the
      expense of the necrotrophic stage of pathogenesis. Like other apoplastic fungi
      Rhynchosporium colonizes the intercellular matrix of host leaves relatively
      slowly without causing symptoms, reminiscent of the development of endophytic
      fungi. Rhynchosporium may therefore become an object for studying the mutualism
      parasitism transition.

PMID- 27875984
TI  - Plastid: nucleotide-resolution analysis of next-generation sequencing and
      genomics data.
AB  - BACKGROUND: Next-generation sequencing (NGS) informs many biological questions
      with unprecedented depth and nucleotide resolution. These assays have created a
      need for analytical tools that enable users to manipulate data nucleotide-by
      nucleotide robustly and easily. Furthermore, because many NGS assays encode
      information jointly within multiple properties of read alignments - for example,
      in ribosome profiling, the locations of ribosomes are jointly encoded in
      alignment coordinates and length - analytical tools are often required to extract
      the biological meaning from the alignments before analysis. Many assay-specific
      pipelines exist for this purpose, but there remains a need for user-friendly,
      generalized, nucleotide-resolution tools that are not limited to specific
      experimental regimes or analytical workflows. RESULTS: Plastid is a Python
      library designed specifically for nucleotide-resolution analysis of genomics and
      NGS data. As such, Plastid is designed to extract assay-specific information from
      read alignments while retaining generality and extensibility to novel NGS assays.
      Plastid represents NGS and other biological data as arrays of values associated
      with genomic or transcriptomic positions, and contains configurable tools to
      convert data from a variety of sources to such arrays. Plastid also includes
      numerous tools to manipulate even discontinuous genomic features, such as spliced
      transcripts, with nucleotide precision. Plastid automatically handles conversion
      between genomic and feature-centric coordinates, accounting for splicing and
      strand, freeing users of burdensome accounting. Finally, Plastid's data models
      use consistent and familiar biological idioms, enabling even beginners to develop
      sophisticated analytical workflows with minimal effort. CONCLUSIONS: Plastid is a
      versatile toolkit that has been used to analyze data from multiple NGS assays,
      including RNA-seq, ribosome profiling, and DMS-seq. It forms the genomic engine
      of our ORF annotation tool, ORF-RATER, and is readily adapted to novel NGS
      assays. Examples, tutorials, and extensive documentation can be found at
      https://plastid.readthedocs.io .

PMID- 27875985
TI  - Nuclear envelope structural defect underlies the main cause of aneuploidy in
      ovarian carcinogenesis.
AB  - BACKGROUND: The Cancer Atlas project has shown that p53 is the only commonly (96
      %) mutated gene found in high-grade serous epithelial ovarian cancer, the major
      histological subtype. Another general genetic change is extensive aneuploidy
      caused by chromosomal numerical instability, which is thought to promote
      malignant transformation. Conventionally, aneuploidy is thought to be the result
      of mitotic errors and chromosomal nondisjunction during mitosis. Previously, we
      found that ovarian cancer cells often lost or reduced nuclear lamina proteins
      lamin A/C, and suppression of lamin A/C in cultured ovarian epithelial cells
      leads to aneuploidy. Following up, we investigated the mechanisms of lamin A/C
      suppression in promoting aneuploidy and synergy with p53 inactivation. RESULTS:
      We found that suppression of lamin A/C by siRNA in human ovarian surface
      epithelial cells led to frequent nuclear protrusions and formation of
      micronuclei. Lamin A/C-suppressed cells also often underwent mitotic failure and
      furrow regression to form tetraploid cells, which frequently underwent aberrant
      multiple polar mitosis to form aneuploid cells. In ovarian surface epithelial
      cells isolated from p53 null mice, transient suppression of lamin A/C produced
      massive aneuploidy with complex karyotypes, and the cells formed malignant tumors
      when implanted in mice. CONCLUSIONS: Based on the results, we conclude that a
      nuclear envelope structural defect, such as the loss or reduction of lamin A/C
      proteins, leads to aneuploidy by both the formation of tetraploid intermediates
      following mitotic failure, and the reduction of chromosome (s) following nuclear
      budding and subsequent loss of micronuclei. We suggest that the nuclear envelope
      defect, rather than chromosomal unequal distribution during cytokinesis, is the
      main cause of aneuploidy in ovarian cancer development.

PMID- 27875986
TI  - The retardant effect of 2-Tridecanone, mediated by Cytochrome P450, on the
      Development of Cotton bollworm, Helicoverpa armigera.
AB  - BACKGROUND: Plant allelochemicals act as toxins, inhibitors of digestion, and
      deterrents that affect the fecundity of insects. These compounds have attracted
      significant research attention in recent decades, and much is known about the
      effects of these xenobiotic plant secondary metabolites on insect development. To
      date, although ecological interactions between xenobiotic plant secondary
      chemicals that retard insect growth have been observed in many species, it
      remains unclear how particular allelochemicals influence insect development in a
      life stage-dependent manner. RESULTS: We found that 2-tridecanone can affect
      insect development; this effect appears similar to the symptoms induced by the
      physiological imbalance between juvenile and molting hormones in cotton bollworm.
      We later detected that a decrease in the concentration of 20-hydroxyecdysone
      occurred alongside the observed symptoms. We next identified the transcriptome of
      Helicoverpa armigera and eightdigital gene expression libraries for shading light
      on how 2-tridecanone retarded the development of cotton bollworm. The expression
      of CYP314A1, CYP315A1, CYP18A1, CYP307A1, and CYP306A1 (unigenes 16487, 15409,
      40026, 41217, 35643, 16953, 8199, 13311, and 13036) were found to be induced by 2
      tridecanone; these are known to be related to the biosynthesis or metabolism of
      20-hydroxyecdysone. Expression analysis and RNA interference studies established
      that the retardant effect of 2-tridecanone on the development of cotton bollworm
      is mediated by P450 genes. CONCLUSIONS: The candidate P450 gene approach
      described and exploited here is useful for identifying potential causal genes for
      the influence of plant allelochemicals on insect development.

PMID- 27875987
TI  - Biomarkers of cardiovascular injury and stress are associated with increased
      frequency of ventricular ectopy: a population-based study.
AB  - BACKGROUND: Asymptomatic ventricular arrhythmias are common and associated with
      increased risk of cardiovascular mortality. Cardiac troponins, natriuretic
      peptides and C-reactive protein (CRP) are also predictive of adverse
      cardiovascular events in the general population, but limited information is
      available on the relationship between these biomarkers and ventricular ectopy in
      a community-based population. The objectives were to evaluate the associations
      between ventricular ectopic activity and N-terminal pro-B-type natriuretic
      peptide (NT-proBNP), high sensitivity-troponin I (hs-TnI) and hs-CRP in a
      community-based setting. METHODS: We performed a 24 h Holter-recording and blood
      sampling in 498 subjects. Premature ventricular complexes (PVC) were classified
      as frequent at >5/h and the presence of any bigeminy, trigeminy or non-sustained
      ventricular tachycardia were classified as complex ventricular ectopy. The
      associations between biomarkers and ventricular arrhythmias were investigated by
      univariate and multivariate logistic regression analyses. RESULTS: Frequent PVC's
      and complex ventricular ectopy were detected in 46 (9%) and 47 (9%) participants
      respectively, and were associated with significantly (p < 0.001) higher
      concentrations of NT-proBNP and hs-TnI. The association between NT-proBNP and
      both frequent PVC's (p = 0.020) and complex ventricular ectopy (p = 0.001)
      remained significant after adjusting for conventional risk markers in
      multivariate analyses. CONCLUSION: Increased level of NT-proBNP was independently
      associated with ventricular ectopy, whereas no independent association was
      observed between hs-TnI and hs-CRP levels and ventricular ectopy in this
      community-based sample.

PMID- 27875988
TI  - Common data elements for secondary use of electronic health record data for
      clinical trial execution and serious adverse event reporting.
AB  - BACKGROUND: Data capture is one of the most expensive phases during the conduct
      of a clinical trial and the increasing use of electronic health records (EHR)
      offers significant savings to clinical research. To facilitate these secondary
      uses of routinely collected patient data, it is beneficial to know what data
      elements are captured in clinical trials. Therefore our aim here is to determine
      the most commonly used data elements in clinical trials and their availability in
      hospital EHR systems. METHODS: Case report forms for 23 clinical trials in
      differing disease areas were analyzed. Through an iterative and consensus-based
      process of medical informatics professionals from academia and trial experts from
      the European pharmaceutical industry, data elements were compiled for all disease
      areas and with special focus on the reporting of adverse events. Afterwards, data
      elements were identified and statistics acquired from hospital sites providing
      data to the EHR4CR project. RESULTS: The analysis identified 133 unique data
      elements. Fifty elements were congruent with a published data inventory for
      patient recruitment and 83 new elements were identified for clinical trial
      execution, including adverse event reporting. Demographic and laboratory elements
      lead the list of available elements in hospitals EHR systems. For the reporting
      of serious adverse events only very few elements could be identified in the
      patient records. CONCLUSIONS: Common data elements in clinical trials have been
      identified and their availability in hospital systems elucidated. Several
      elements, often those related to reimbursement, are frequently available whereas
      more specialized elements are ranked at the bottom of the data inventory list.
      Hospitals that want to obtain the benefits of reusing data for research from
      their EHR are now able to prioritize their efforts based on this common data
      element list.

PMID- 27875989
TI  - Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption.
AB  - BACKGROUND: Sleep disruptions are common in epilepsy patients. Our previous study
      demonstrates that homeostatic factors and circadian rhythm may mediate epilepsy
      induced sleep disturbances when epilepsy occurs at different zeitgeber hours. The
      proinflammatory cytokine, interleukin-1 (IL-1), is a somnogenic cytokine and may
      also be involved in epileptogenesis; however, few studies emphasize the effect of
      IL-1 in epilepsy-induced sleep disruption. We herein hypothesized that IL-1
      receptor type 1 (IL-1R1) mediates the pathogenesis of epilepsy and epilepsy
      induced sleep disturbances. We determined the role of IL-1R1 by using IL-1R1
      knockout (IL-1R1 -/- KO) mice. RESULTS: Our results elucidated the decrease of
      non-rapid eye movement (NREM) sleep during the light period in IL-1R -/- mice and
      confirmed the somnogenic role of IL-1R1. Rapid electrical amygdala kindling was
      performed to induce epilepsy at the particular zeitgeber time (ZT) point, ZT13.
      Our results demonstrated that seizure thresholds induced by kindling stimuli,
      such as the after-discharge threshold and successful kindling rates, were not
      altered in IL-1R -/- mice when compared to those obtained from the wildtype mice
      (IL-1R +/+ mice). This result suggests that IL-1R1 is not involved in kindling
      induced epileptogenesis. During sleep, ZT13 kindling stimulation significantly
      enhanced NREM sleep during the subsequent 6 h (ZT13-18) in wildtype mice, and
      sleep returned to the baseline the following day. However, the kindling-induced
      sleep alteration was absent in the IL-1R -/- KO mice. CONCLUSIONS: These results
      indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but
      dose not participate in kindling-induced epileptogenesis.

PMID- 27875990
TI  - Inverse relationship between Alzheimer's disease and cancer, and other factors
      contributing to Alzheimer's disease: a systematic review.
AB  - BACKGROUND: The AD etiology is yet not properly known. Interactions among
      environmental factors, multiple susceptibility genes and aging, contribute to AD.
      This study investigates the factors that play role in causing AD and how changes
      in cellular pathways contribute to AD. METHODS: PUBMED database, MEDLINE database
      and Google Scholar were searched with no date restrictions for published articles
      involving cellular pathways with roles in cancers, cell survival, growth,
      proliferation, development, aging, and also contributing to Alzheimer's disease.
      This research explores inverse relationship between AD and cancer, also
      investigates other factors behind AD using several already published research
      literature to find the etiology of AD. RESULTS: Cancer and Alzheimer's disease
      have inverse relationship in many aspects such as P53, estrogen, neurotrophins
      and growth factors, growth and proliferation, cAMP, EGFR, Bcl-2, apoptosis
      pathways, IGF-1, HSV, TDP-43, APOE variants, notch signals and presenilins, NCAM,
      TNF alpha, PI3K/AKT/MTOR pathway, telomerase, ROS, ACE levels. AD occurs when
      brain neurons have weakened growth, cell survival responses, maintenance
      mechanisms, weakened anti-stress responses such as Vimentin, Carbonic anhydrases,
      HSPs, SAPK. In cancer, these responses are upregulated and maintained.
      Evolutionarily conserved responses and maintenance mechanisms such as FOXO are
      impaired in AD. Countermeasures or compensatory mechanisms by AD affected neurons
      such as Tau, Beta Amyloid, S100, are last attempts for survival which may be
      protective for certain time, or can speed up AD in Alzheimer's microenvironment
      via C-ABL activation, GSK3, neuro-inflammation. CONCLUSIONS: Alzheimer's disease
      and Cancer have inverse relationship; many factors that are upregulated in any
      cancer to sustain growth and survival are downregulated in Alzheimer's disease
      contributing to neuro-degeneration. When aged neurons or genetically susceptible
      neurons have weakened growth, cell survival and anti-stress responses, age
      related gene expression changes, altered regulation of cell death and maintenance
      mechanisms, they contribute to Alzheimer's disease. Countermeasures by AD neurons
      such as Beta Amyloid Plaques, NFTs, S100, are last attempts for survival and this
      provides neuroprotection for certain time and ultimately may become pathological
      and speed up AD. This study may contribute in developing new potential diagnostic
      tests, interventions and treatments.

PMID- 27875991
TI  - The prevalence of renal impairment in individuals seeking HIV testing in Urban
      Malawi.
AB  - BACKGROUND: Chronic kidney disease (CKD) poses a major health threat to people
      living in low- and middle-income countries, especially when it is combined with
      HIV, antiretroviral treatment (ART) or communicable and non-communicable
      diseases. Data about the prevalence of CKD and its association with other
      diseases is scarce, particularly in HIV-negative individuals. This study
      estimated the prevalence of CKD in individuals who were either HIV-positive (and
      ART-naive) or HIV-negative in an urban Malawian population. METHODS: This cross
      sectional study was conducted at a HIV Testing and Counselling Centre in
      Lilongwe, Malawi. Consecutive clients who were >=18 years and consented to
      participate were enrolled over a 3-month period. Clients were screened for
      potential renal disease and other conditions. Their blood pressure was measured,
      urine examined via dipstick and albumin/creatinine ratio and blood drawn for
      creatinine, cystatin C and sero-markers for schistosomiasis. Estimated glomerular
      filtration (eGFR) rate was calculated using a cystatin C-based formula and
      classified according to the matching CKD stages by K/DOQI (The National Kidney
      Foundation Kidney Disease Outcome Quality Initiative). We performed a descriptive
      analysis and compared differences between HIV-positive (and ART naive) and 
      negative participants. RESULTS: Out of 381 consecutive clients who were
      approached between January and March 2012, 366 consented and 363 (48% female; 32%
      HIV-positive) were included in the analysis. Reasons for exclusion were missing
      samples or previous use of ART. HIV-positive and negative clients did not differ
      significantly with regard to age, sex or medical history, but they did differ for
      BMI-21.3 (+/-3.4) vs. 24 (+/-5.1), respectively (p < 0.001). Participants also
      differed with regard to serum cystatin C levels, but not creatinine. Reduced
      kidney function (according to CKD stages 2-5) was significantly more frequent
      15.5 vs. 3.6%, respectively (p < 0.001) among HIV-positive clients compared to
      the HIV-negative group. Differences in renal function were most pronounced in the
      eGFR range 60-89 ml/min/1.73 m2 accompanied by proteinuria with results as 11.2%
      vs. 1.2%, respectively for clients who were HIV-positive vs. HIV-negative (p =
      0.001). CONCLUSIONS: Reduced glomerular filtration and/or proteinuria occurred in
      15.5% of HIV-positive, and 3.6% of HIV-negative patients in this urban Malawian
      cohort. Since generalized renal monitoring is not feasible in Malawi or other
      resource-limited countries, strategies to identify patients at risk for higher
      stages of CKD and appropriate preventive measures are needed for both HIV
      positive and HIV-negative patients.

PMID- 27875992
TI  - Optimizing literature search in systematic reviews - are MEDLINE, EMBASE and
      CENTRAL enough for identifying effect studies within the area of musculoskeletal
      disorders?
AB  - BACKGROUND: When conducting systematic reviews, it is essential to perform a
      comprehensive literature search to identify all published studies relevant to the
      specific research question. The Cochrane Collaborations Methodological
      Expectations of Cochrane Intervention Reviews (MECIR) guidelines state that
      searching MEDLINE, EMBASE and CENTRAL should be considered mandatory. The aim of
      this study was to evaluate the MECIR recommendations to use MEDLINE, EMBASE and
      CENTRAL combined, and examine the yield of using these to find randomized
      controlled trials (RCTs) within the area of musculoskeletal disorders. METHODS:
      Data sources were systematic reviews published by the Cochrane Musculoskeletal
      Review Group, including at least five RCTs, reporting a search history, searching
      MEDLINE, EMBASE, CENTRAL, and adding reference- and hand-searching. Additional
      databases were deemed eligible if they indexed RCTs, were in English and used in
      more than three of the systematic reviews. Relative recall was calculated as the
      number of studies identified by the literature search divided by the number of
      eligible studies i.e. included studies in the individual systematic reviews.
      Finally, cumulative median recall was calculated for MEDLINE, EMBASE and CENTRAL
      combined followed by the databases yielding additional studies. RESULTS: Deemed
      eligible was twenty-three systematic reviews and the databases included other
      than MEDLINE, EMBASE and CENTRAL was AMED, CINAHL, HealthSTAR, MANTIS, OT-Seeker,
      PEDro, PsychINFO, SCOPUS, SportDISCUS and Web of Science. Cumulative median
      recall for combined searching in MEDLINE, EMBASE and CENTRAL was 88.9% and
      increased to 90.9% when adding 10 additional databases. CONCLUSION: Searching
      MEDLINE, EMBASE and CENTRAL was not sufficient for identifying all effect studies
      on musculoskeletal disorders, but additional ten databases did only increase the
      median recall by 2%. It is possible that searching databases is not sufficient to
      identify all relevant references, and that reviewers must rely upon additional
      sources in their literature search. However further research is needed.

PMID- 27875994
TI  - Do primary care professionals agree about progress with implementation of primary
      care teams: results from a cross sectional study.
AB  - BACKGROUND: Primary care is the cornerstone of healthcare reform with policies
      across jurisdictions promoting interdisciplinary team working. The effective
      implementation of such health policies requires understanding the perspectives of
      all actors. However, there is a lack of research about health professionals'
      views of this process. This study compares Primary Healthcare Professionals'
      perceptions of the effectiveness of the Primary Care Strategy and Primary Care
      Team (PCT) implementation in Ireland. METHODS: Design and Setting: e-survey of
      (1) General Practitioners (GPs) associated with a Graduate Medical School (N =
      100) and (2) Primary Care Professionals in 3 of 4 Health Service Executive (HSE)
      regions (N = 2309). After piloting, snowball sampling was used to administer the
      survey. Descriptive analysis was carried out using SPSS. Ratings across groups
      were compared using non-parametric tests. RESULTS: There were 569 responses.
      Response rates varied across disciplines (71 % for GPs, 22 % for other Primary
      Healthcare Professionals (PCPs). Respondents across all disciplines viewed
      interdisciplinary working as important. Respondents agreed on lack of progress of
      implementation of formal PCTs (median rating of 2, where 1 is no progress at all
      and 5 is complete implementation). GPs were more negative about the effectiveness
      of the Strategy to promote different disciplines to work together (median rating
      of 2 compared to 3 for clinical therapists and 3.5 for nurses, P = 0.001).
      Respondents identified resources and GP participation as most important for
      effective team working. Protected time for meetings and capacity to manage
      workload for meetings were rated as very important factors for effective team
      working by GPs, clinical therapists and nurses. A building for co-location of
      teams was rated as an important factor by nurses and clinical therapists though
      GPs rated it as less important. Payment to attend meetings and contractual
      arrangements were considered important factors by GPs but not by nurses or
      clinical therapists. CONCLUSION: PCPs and GPs agree there is limited PCT
      implementation. GPs are most negative about this implementation. There is some
      disagreement about which resources are most important for effective PCT working.
      These findings provide valuable data for clinicians and policy makers about
      implementation of interdisciplinary teams in primary care.

PMID- 27875993
TI  - A transcriptome-based model of central memory CD4 T cell death in HIV infection.
AB  - BACKGROUND: Human central memory CD4 T cells are characterized by their capacity
      of proliferation and differentiation into effector memory CD4 T cells.
      Homeostasis of central memory CD4 T cells is considered a key factor sustaining
      the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection,
      while progression to acquired immunodeficiency syndrome is imputed to central
      memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T
      cells from patients with HIV-1 infection have a gene expression profile impeding
      proliferation and survival, despite their activated state. METHODS: Using gene
      expression microarrays, we analyzed mRNA expression patterns in naive, central
      memory, and effector memory CD4 T cells from healthy controls, and naive and
      central memory CD4 T cells from patients with HIV-1 infection. Differentially
      expressed genes, defined by Log2 Fold Change (FC) >= |0.5| and Log (odds) > 0,
      were used in pathway enrichment analyses. RESULTS: Central memory CD4 T cells
      from patients and controls showed comparable expression of differentiation
      related genes, ruling out an effector-like differentiation of central memory CD4
      T cells in HIV infection. However, 210 genes were differentially expressed in
      central memory CD4 T cells from patients compared with those from controls.
      Expression of 75 of these genes was validated by semi quantitative RT-PCR, and
      independently reproduced enrichment results from this gene expression signature.
      The results of functional enrichment analysis indicated movement to cell cycle
      phases G1 and S (increased CCNE1, MKI67, IL12RB2, ADAM9, decreased FGF9, etc.),
      but also arrest in G2/M (increased CHK1, RBBP8, KIF11, etc.). Unexpectedly, the
      results also suggested decreased apoptosis (increased CSTA, NFKBIA, decreased
      RNASEL, etc.). Results also suggested increased IL-1beta, IFN-gamma, TNF, and
      RANTES (CCR5) activity upstream of the central memory CD4 T cells signature,
      consistent with the demonstrated milieu in HIV infection. CONCLUSIONS: Our
      findings support a model where progressive loss of central memory CD4 T cells in
      chronic HIV-1 infection is driven by increased cell cycle entry followed by
      mitotic arrest, leading to a non-apoptotic death pathway without actual
      proliferation, possibly contributing to increased turnover.

PMID- 27875995
TI  - High-throughput gene-expression quantification of grapevine defense responses in
      the field using microfluidic dynamic arrays.
AB  - BACKGROUND: The fight against grapevine diseases due to biotrophic pathogens
      usually requires the massive use of chemical fungicides with harmful
      environmental effects. An alternative strategy could be the use of compounds able
      to stimulate plant immune responses which significantly limit the development of
      pathogens in laboratory conditions. However, the efficiency of this strategy in
      natura is still insufficient to be included in pest management programs. To
      understand and to improve the mode of action of plant defense stimulators in the
      field, it is essential to develop reliable tools that describe the resistance
      status of the plant upon treatment. RESULTS: We have developed a pioneering tool
      ("NeoViGen96" chip) based on a microfluidic dynamic array platform allowing the
      expression profiling of 85 defense-related grapevine genes in 90 cDNA
      preparations in a 4 h single run. Two defense inducers, benzothiadiazole (BTH)
      and fosetyl-aluminum (FOS), have been tested in natura using the "NeoViGen96"
      chip as well as their efficacy against downy mildew. BTH-induced grapevine
      resistance is accompanied by the induction of PR protein genes (PR1, PR2 and
      PR3), genes coding key enzymes in the phenylpropanoid pathway (PAL and STS), a
      GST gene coding an enzyme involved in the redox status and an ACC gene involved
      in the ethylene pathway. FOS, a phosphonate known to possess a toxic activity
      against pathogens and an inducing effect on defense genes provided a better
      grapevine protection than BTH. Its mode of action was probably strictly due to
      its fungicide effect at high concentrations because treatment did not induce
      significant change in the expression level of selected defense-related genes.
      CONCLUSIONS: The NeoViGen96" chip assesses the effectiveness of plant defense
      inducers on grapevine in vineyard with an excellent reproducibility. A single run
      with this system (4 h and 1,500 ?), corresponds to 180 qPCR plates with
      conventional Q-PCR assays (Stragene system, 270 h and 9,000 ?) thus a throughput
      60-70 times higher and 6 times cheaper. Grapevine responses after BTH elicitation
      in the vineyard were similar to those obtained in laboratory conditions, whereas
      our results suggest that the protective effect of FOS against downy mildew in the
      vineyard was only due to its fungicide activity since no activity on plant
      defense genes was observed. This tool provides better understanding of how the
      grapevine replies to elicitation in its natural environment and how the elicitor
      potential can be used to reduce chemical fungicide inputs.

PMID- 27875998
TI  - Transcriptome profiling and comparison of maize ear heterosis during the spikelet
      and floret differentiation stages.
AB  - BACKGROUND: Hybridization is a prominent process in the evolution of crop plants
      that can give rise to gene expression variation, phenotypic novelty and
      heterosis. Maize is the most successful crop in utilizing heterosis. The
      development of hybrid maize ears exhibits strong heterotic vigor and greatly
      affects maize yield. However, a comprehensive perspective on transcriptional
      variation and its correlation with heterosis during maize ear development is not
      available. RESULTS: Using RNA sequencing technology, we investigated the
      transcriptome profiles of maize ears in the spikelet and floret differentiation
      stages of hybrid ZD808 and its parents CL11 and NG5. Our results revealed that
      53.9% (21,258) of maize protein-coding genes were transcribed in at least one
      genotype. In both development stages, significant numbers of genes were
      differentially expressed between the hybrid and its parents. Gene expression
      inheritance analysis revealed approximately 80% of genes were expressed
      additively, which suggested that the complementary effect may play a foundation
      role in maize ear heterosis. Among non-additively expressed genes, NG5-dominant
      genes were predominant. Analyses of the allele-specific gene expression in hybrid
      identified pervasive allelic imbalance and significant preferential expression of
      NG5 alleles in both developmental stages. The results implied that NG5 may
      provide beneficial alleles that contribute greatly to heterosis. Further
      comparison of parental and hybrid allele-specific expression suggested that gene
      expression variation is largely attributable to cis-regulatory variation in
      maize. The cis-regulatory variations tend to preserve the allelic expression
      levels in hybrid and result in additive expression. Comparison between the two
      development stages revealed that allele-specific expression and cis-/trans
      regulatory variations responded differently to developmental cues, which may lead
      to stage-specific vigor phenotype during maize ear development. CONCLUSION: Our
      research suggests that cis-regulated additive expression may fine-tune gene
      expression level into an optimal status and play a foundation role in maize ear
      heterosis. Our work provides a comprehensive insight into transcriptional
      variation and its correlation with heterosis during maize ear development. The
      knowledge gained from this study presents novel opportunity to improve our maize
      varieties.

PMID- 27875996
TI  - Differences in the skeletal muscle transcriptome profile associated with extreme
      values of fatty acids content.
AB  - BACKGROUND: Lipids are a class of molecules that play an important role in
      cellular structure and metabolism in all cell types. In the last few decades, it
      has been reported that long-chain fatty acids (FAs) are involved in several
      biological functions from transcriptional regulation to physiological processes.
      Several fatty acids have been both positively and negatively implicated in
      different biological processes in skeletal muscle and other tissues. To gain
      insight into biological processes associated with fatty acid content in skeletal
      muscle, the aim of the present study was to identify differentially expressed
      genes (DEGs) and functional pathways related to gene expression regulation
      associated with FA content in cattle. RESULTS: Skeletal muscle transcriptome
      analysis of 164 Nellore steers revealed no differentially expressed genes (DEGs,
      FDR 10%) for samples with extreme values for linoleic acid (LA) or stearic acid
      (SA), and only a few DEGs for eicosapentaenoic acid (EPA, 5 DEGs),
      docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large
      numbers of DEGs were associated with oleic acid (OA, 1134 DEGs) and conjugated
      linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and
      functional enrichment from OA DEGs identified important genes, canonical pathways
      and upstream regulators such as SCD, PLIN5, UCP3, CPT1, CPT1B, oxidative
      phosphorylation mitochondrial dysfunction, PPARGC1A, and FOXO1. Two important
      genes associated with lipid metabolism, gene expression and cancer were
      identified as DEGs between animals with high and low CLA-c9t11, specifically,
      epidermal growth factor receptor (EGFR) and RNPS. CONCLUSION: Only two out of
      seven classes of molecules of FA studied were associated with large changes in
      the expression profile of skeletal muscle. OA and CLA-c9t11 content had
      significant effects on the expression level of genes related to important
      biological processes associated with oxidative phosphorylation, and cell growth,
      survival, and migration. These results contribute to our understanding of how
      some FAs modulate metabolism and may have protective health function.

PMID- 27875997
TI  - Identification of the transcripts associated with spontaneous HCV clearance in
      individuals co-infected with HIV and HCV.
AB  - BACKGROUND: Infection with human immunodeficiency virus (HIV) influences the
      outcome and natural disease progression of hepatitis C virus (HCV) infection.
      While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop
      chronic HCV infection, 20-46% of mono- and co-infected subjects spontaneously
      clear HCV infection. The mechanism underlying viral clearance is not clearly
      understood. Analysis of differential cellular gene expression (mRNA) between HIV
      infected patients with persistent HCV infection or spontaneous clearance could
      provide a unique opportunity to decipher the mechanism of HCV clearance. METHODS:
      Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who
      remained chronically infected with HCV was sequenced using Ion Torrent
      technology. The sequencing results were analyzed to identify transcripts that are
      associated with HCV clearance by measuring differential gene expression in
      HIV/HCV co-infected subjects who cleared HCV and those who remained chronically
      infected with HCV. RESULTS: We have identified plasma mRNA, the levels of which
      are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05)
      before HCV infection in subjects who cleared HCV compared to those who remained
      chronically infected. Upon further analysis of these differentially expressed
      genes, before and after HCV infection, we found that before HCV infection 12
      genes were uniquely upregulated in the clearance group compared to the
      chronically infected group. Importantly, a number of these 12 genes and their
      upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are
      associated with innate immune response functions. CONCLUSIONS: These results
      suggest that subjects who spontaneously clear HCV may express these unique genes
      associated with innate immune functions.

PMID- 27876000
TI  - Comparison of repair of peripheral nerve transection in predegenerated muscle
      with and without a vein graft.
AB  - BACKGROUND: Despite substantial research into the topic and valiant surgical
      efforts, reconstruction of peripheral nerve injury remains a challenging surgery.
      This study was conducted to evaluate the effectiveness of axonal regeneration of
      a transected sciatic nerve through a vein conduit containing degenerated skeletal
      muscle compared with axonal regeneration in a transected sciatic nerve through
      degenerated skeletal muscle alone. METHODS: In two of the three experimental rat
      groups, 10 mm of the left sciatic nerve was transected and removed. The proximal
      and distal ends of the transected sciatic nerve were then approximated and
      surrounded with either (a) a degenerated skeletal muscle graft; or (b) a graft
      containing both degenerated skeletal muscle and vein. In the group receiving the
      combined vein and skeletal muscle graft, the vein walls were subsequently sutured
      to the proximal and distal nerve stump epineurium. Sciatic functional index (SFI)
      was used for assessment of functional recovery. Tracing study and histological
      procedures were used to assess axonal regeneration. RESULTS: At 60 days, the gait
      functional recovery as well as the mean number of myelinated axons in the middle
      and distal parts of the sciatic nerve significantly increased in the group with
      the vein graft compared to rats with only the muscular graft (P < 0.05). Mean
      diameter of myelinated nerve fiber of the distal sciatic nerve was also improved
      with the vein graft compared to the muscle graft alone (P < 0.05). The mean
      number of DiI-labeled motor neurons in the L4-L5 spinal segment increased in the
      vein with muscle group but was not significantly different between the two
      groups. CONCLUSIONS: These findings demonstrated that a graft consisting of not
      only predegenerated muscle, but also predegenerated muscle with vein more
      effectively supported nerve regeneration, thus promoting functional recovery
      after sciatic nerve injury in rats.

PMID- 27876001
TI  - Severe mitral regurgitation due to mitral leaflet aneurysm diagnosed by three
      dimensional transesophageal echocardiography: a case report.
AB  - BACKGROUND: A small mitral valve aneurysm (MVA) presenting as severe mitral
      regurgitation (MR) is uncommon. CASE PRESENTATION: A 47-year-old man with a
      history of hypertension complained of exertional chest discomfort. A
      transthoracic echocardiogram (TTE) revealed the presence of MR and prolapse of
      the posterior leaflet. A 6-mm in diameter MVA, not clearly visualized by TTE, was
      detected on the posterior leaflet on a three-dimensional (3D) transesophageal
      echocardiography (TEE). The patient underwent uncomplicated triangular resection
      of P2 and mitral valve annuloplasty, and was discharged from postoperative
      rehabilitation, 2 weeks after the operation. Histopathology of the excised
      leaflet showed myxomatous changes without infective vegetation or signs of
      rheumatic heart disease. CONCLUSIONS: A small, isolated MVA is a cause of severe
      MR, which might be overlooked and, therefore, managed belatedly. 3D TEE was
      helpful in imaging its morphologic details.

PMID- 27876002
TI  - Sporadic Creutzfeldt-Jakob disease with unusual initial presentation as posterior
      reversible encephalopathy syndrome: a case report.
AB  - BACKGROUND: Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal
      neurodegenerative prion disease. MRI findings are included in diagnostic criteria
      for probable CJD, giving a sensitivity and specificity more than 90%, but the
      atypical radiological presentations in the early stage of the disease could cause
      the diagnostic difficulties. CJD can be definitively diagnosed by
      histopathological confirmation, brain biopsy or at autopsy. CASE PRESENTATION: We
      present a case of 53-year-old woman with a history of a rapidly progressive
      dementia with symptoms of visual impairment, increased extrapyramidal type muscle
      tonus, stereotypical movements and ataxic gait resulting in the patient's death
      after13 months. The clinical symptoms deteriorated progressively to myoclonus and
      akinetic mutism already on the 14th week. The series of diagnostic examinations
      were done to exclude the possible causes of dementia. Initial MRI evaluation as
      posterior reversible encephalopathy syndrome (PRES) on the 9th week after the
      onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of
      symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th
      week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the
      18th week allowed us to diagnose the probable sCJD. The histopathological
      findings after brain biopsy on the 14th week demonstrated the presence of the
      abnormal prion protein deposits in the grey matter by immunohistochemistry with
      ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD.
      CONCLUSIONS: In this article we focus our attention on a rare association between
      radiological PRES syndrome and early clinical stage of sCJD. Although concurrent
      manifestation of these conditions can be accidental, but the immunogenic or
      neuropeptide mechanisms could explain such radiological MRI findings. A thorough
      knowledge of differential diagnostic of PRES may be especially useful in earlier
      diagnosis of sCJD.

PMID- 27875999
TI  - Helping Babies Breathe (HBB) training: What happens to knowledge and skills over
      time?
AB  - BACKGROUND: The first minutes after birth are critical to reducing neonatal
      mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal
      resuscitation program for low resource settings. We studied the impact of initial
      HBB training followed by refresher training on the knowledge and skills of the
      birth attendants in facilities. METHODS: We conducted HBB trainings in 71
      facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India
      and Eldoret, Kenya), with a 6:1 ratio of facility trainees to Master Trainers
      (MT). Because of staff turnover, some birth attendants (BA) were trained as they
      joined the delivery room staff, after the initial training was completed (catch
      up initial training). We compared pass rates for skills and knowledge pre- and
      post- initial HBB training and following refresher training among active BAs. An
      Objective Structured Clinical Examination (OSCE) B tested resuscitation skill
      retention by comparing post-initial training performance with pre-refresher
      training performance. We identified factors associated with loss of skills in pre
      refresher training performance using multivariable logistic regression analysis.
      Daily bag and mask ventilation practice, equipment checks and supportive
      supervision were stressed as part of training. RESULTS: One hundred five MT (1.6
      MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76%
      had no prior resuscitation training. Initial training improved knowledge and
      skills: the pass percentage for knowledge tests improved from 74 to 99% (p <
      0.001). Only 5% could ventilate a newborn mannequin correctly before initial
      training but 97% passed the post-initial ventilation training test (p < 0.0001)
      and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training
      evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed
      the knowledge test, but the successful completion rate fell to 81% for the OSCE B
      resuscitation skills test. Characteristics associated with deterioration of
      resuscitation skills were BAs from tertiary care facilities, no prior
      resuscitation training, and the timing of training (initial vs. catch-up
      training). CONCLUSIONS: HBB training significantly improved neonatal
      resuscitation knowledge and skills. However, skills declined more than knowledge
      over time. Ongoing skills practice and monitoring, more frequent retesting, and
      refresher trainings are needed to maintain neonatal resuscitation skills. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01681017 ; 04 September 2012,
      retrospectively registered.

PMID- 27876003
TI  - PLA2R antibodies and PLA2R glomerular deposits in psoriasis patients with
      membranous nephropathy.
AB  - BACKGROUND: The association between psoriasis and membranous nephropathy (MN)
      remains largely unclear. We examined the prevalence of serum PLA2R antibody and
      characterized the expression of PLA2R and THSD7A in glomeruli in patients with MN
      and psoriasis. METHODS: A total of 24 patients with MN without evidence of a
      secondary cause except psoriasis were enrolled. The clinical and pathological
      features were retrospectively analyzed. Serum anti-PLA2R antibody was measured
      using IFA Mosaic. Renal tissue samples stored in the laboratory bio-bank were
      used for PLA2R staining under immunofluorescence microscopy and THSD7A
      immunohistochemical analysis. RESULTS: Twenty-four patients (21 male and 3
      female) with a mean age of 43.6 +/- 15.7 years old were enrolled. Serum anti
      PLA2R antibody was positive in 7 patients, which was significantly lower than the
      positivity observed in idiopathic MN (29.2% vs. 81.7%, P < 0.001). Glomerular
      PLA2R staining was positive in 7 patients with positive serum anti-PLA2R
      antibody. THSD7A staining was negative in all 24 patients. During the follow-up
      visits, 13 patients with negative serum PLA2R antibody achieved CR. In contrast,
      CR was only achieved in 1 patient with positive serum PLA2R antibody, PR was
      achieved in 2 patients. CONCLUSIONS: The prevalence of serum anti-PLA2R antibody
      and glomerular expression of PLA2R was significantly lower in patients with
      psoriasis and MN than in those with idiopathic MN, and THSD7A staining was
      negative, suggesting that MN is associated with psoriasis in the majority of
      patients. However, idiopathic MN might also accompany psoriasis in a minority of
      psoriatic patients with positive serum anti-PLA2R antibody.

PMID- 27876005
TI  - A predictive model to differentiate dengue from other febrile illness.
AB  - BACKGROUND: Dengue is a major public health problem in tropical and subtropical
      countries and has a presentation similar to other febrile illnesses. Since
      laboratory confirmation is frequently delayed, the majority of dengue cases are
      diagnosed based on symptoms. The objective of this study was to identify
      clinical, hematological and demographical parameters that could be used as
      predictors of dengue fever among patients with febrile illness. METHODS: We
      conducted a retrospective cohort study of 548 patients presenting with febrile
      syndrome to the largest public hospitals in Honduras. Patients' clinical,
      laboratory, and demographic data as well as dengue laboratory detection by either
      serology or viral isolation were used to build a predictive statistical model to
      identify dengue cases. RESULTS: Of 548 patients, 390 were confirmed with dengue
      infection while 158 had negative results. Univariable analysis revealed seven
      variables associated with dengue: male sex, petechiae, skin rash, myalgia, retro
      ocular pain, positive tourniquet test, and gingival bleeding. In multivariable
      logistic regression analysis, retro-ocular pain petechiae and gingival bleeding
      were associated with increased risk, while epistaxis and paleness of skin were
      associated with reduced risk of dengue. Using a value of 0.6 (i.e., 60%
      probability for a case to be positive based on the equation values), our model
      had a sensitivity of 86.2%, a specificity of 27.2%, and an overall accuracy of
      69.2%; allowing for the diagnosis of dengue to be ruled out and for other febrile
      conditions to be investigated. CONCLUSIONS: Among Honduran patients presenting
      with febrile illness, our analysis identified key symptoms associated with dengue
      fever, however the overall accuracy of our model was still low and specificity
      remains a concern. Our model requires validation in other populations with a
      similar pattern of dengue transmission.

PMID- 27876004
TI  - Enoxaparin for the prevention of preeclampsia and intrauterine growth restriction
      in women with a prior history - an open-label randomised trial (the EPPI trial):
      study protocol.
AB  - BACKGROUND: Preeclampsia and intrauterine fetal growth restriction (IUGR) are two
      of the most common causes of maternal and perinatal morbidity and mortality.
      Current methods of predicting those at most risk of these conditions remain
      relatively poor, and in clinical practice past obstetric history remains the most
      commonly used tool. Aspirin and, in women at risk of preeclampsia only, calcium
      have been demonstrated to have a modest effect on risk reduction. Several
      observational studies and randomised trials suggest that low molecular weight
      heparin (LMWH) therapy may confer some benefit. METHODS/DESIGN: This is a
      multicentre open label randomised controlled trial to determine the effect of the
      LMWH, enoxaparin, on the prevention of recurrence of preeclampsia and/or IUGR in
      women at high risk due to their past obstetric history in addition to standard
      high risk care for all participants. INCLUSION CRITERIA: A singleton pregnancy
      >6+0 and <16+0 weeks gestation with most recent prior pregnancy with duration >12
      weeks having; (1) preeclampsia delivered <36+0 weeks, (2) Small for gestational
      age (SGA) infant <10th customised birthweight centile delivered <36+0 weeks or,
      (3) SGA infant <=3rd customised birthweight centile delivered at any gestation.
      Randomisation is stratified for maternal thrombophilia status and women are
      randomly assigned to 'standard high risk care' or 'standard high risk care' plus
      enoxaparin 40 mg from recruitment until 36+0 weeks or delivery, whichever occurs
      sooner. Standard high risk care includes the use of aspirin 100 mg daily and
      calcium 1000-1500 mg daily (unless only had previous SGA with no preeclampsia).
      The primary outcome is preeclampsia and/or SGA <5th customised birthweight
      centile. Analysis will be by intention to treat. DISCUSSION: The EPPI trial has
      more focussed and clinically relevant inclusion criteria than other randomised
      trials with a more restricted composite primary outcome. The inclusion of
      standard use of aspirin (and calcium) for all participants will help to ensure
      that any differences observed in outcome are likely to be related to enoxaparin
      use. These data will make a significant contribution to future meta-analyses and
      systematic reviews on the use of LMWH for the prevention of placental mediated
      conditions. TRIAL REGISTRATION: ACTRN12609000699268 Australian New Zealand
      Clinical Trials Registry. Date registered 13/Aug/2009 (prospective registration).

PMID- 27876006
TI  - Predictors of in-hospital mortality following major lower extremity amputations
      in type 2 diabetic patients using artificial neural networks.
AB  - BACKGROUND: Outcome prediction is important in the clinical decision-making
      process. Artificial neural networks (ANN) have been used to predict the risk of
      post-operative events, including survival, and are increasingly being used in
      complex medical decision making. We aimed to use ANN analysis to estimate
      predictive factors of in-hospital mortality (IHM) in patients with type 2
      diabetes (T2DM) after major lower extremity amputation (LEA) in Spain. METHODS:
      We design a retrospective, observational study using ANN models. We used the
      Spanish National Hospital Discharge Database to select all hospital admissions of
      major LEA procedure in T2DM patients. MAIN OUTCOME MEASURES: Predictors of IHM
      using 4 ANN models: i) with all discharge diagnosis included in the database; ii)
      with all discharge diagnosis included in the database, excluding infectious
      diseases; iii) comorbidities included in the Charlson Comorbidities Index; iv)
      comorbidities included in the Elixhauser Comorbidity Index. RESULTS: From 2003 to
      2013, 40,857 major LEAs in patients with T2DM were identified with a 10.0% IHM.
      We found that Elixhauser Comorbidity Index model performed better in terms of
      sensitivity, specificity and precision than Charlson Comorbidity Index model
      (0.7634 vs 0.7444; 0.9602 vs 0.9121; 0.9511 vs 0.888, respectively). The area
      under the ROC curve for Elixhauser comorbidity model was 91.7% (95% CI 90.3-93.0)
      and for Charlson comorbidity model was 88.9% (95% CI; 87.590.2) p = 0.043. Models
      including all discharge diagnosis with and without infectious diseases showed
      worse results. In the Elixhauser Comorbidity Index model the most sensitive
      parameter was age (variable sensitive ratio [VSR] 1.451) followed by female sex
      (VSR 1.433), congestive heart failure (VSR 1.341), renal failure (VSR 1.274) and
      chronic pulmonary disease (VSR 1.266). CONCLUSIONS: Elixhauser Comorbidity Index
      is a superior comorbidity risk-adjustment model for major LEA survival prediction
      in patients with T2DM than Charlson Comorbidity Index model using ANN models.
      Female sex, congestive heart failure, and renal failure are strong predictors of
      mortality in these patients.

PMID- 27876007
TI  - Effect of Pregnane X Receptor*1B genetic polymorphisms on postoperative analgesia
      with fentanyl in Chinese patients undergoing gynecological surgery.
AB  - BACKGROUND: The purpose of the study was to investigate the effects of the
      pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and
      postoperative fentanyl consumption in Chinese patients undergoing gynecological
      surgery. METHODS: A total of 287 females of Han ethnicity, aged 20 to 50 years
      old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under
      general anesthesia were enrolled. The analgesic model used was fentanyl
      consumption via patient-controlled intravenous analgesia (PCIA) in the post
      operative period. Additionally, pain was assessed using a visual analog score
      (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl
      were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4
      was evaluated by measuring the plasma ratio of 1'-hydroxymidazolam to midazolam 1
      h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was
      performed by direct DNA sequencing and the PXR * 1B haplotype was analyzed via
      PHASE V.2.1 software. RESULTS: The polymorphism frequency of PXR11156A > C/11193
      T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR * 1B haplotype was
      48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post
      operatively or enzyme activity of CYP3A4, showed differences among different
      genotypes. CONCLUSIONS: PXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR *
      1B haplotype do not appear to be important factors contributing to CYP3A4
      activity and interindividual variations in postoperative fentanyl consumption in
      Han female patients undergoing gynecological surgery. TRIAL REGISTRATION: The DNA
      samples were obtained since 2007 to 2010 year in our hospital, there was no
      registration at that time. So this section is not applicable to our research.

PMID- 27876008
TI  - Physical activity and metabolic health in chronic kidney disease: a cross
      sectional study.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk of
      progression to end stage renal disease and cardiovascular events. Physical
      activity may reduce these risks by improving metabolic health. We tested
      associations of physical activity with central components of metabolic health
      among people with moderate-severe non-diabetic CKD. METHODS: We performed a cross
      sectional study of 47 people with CKD (estimated GFR <60 ml/min/1.73 m2) and 29
      healthy control subjects. Accelerometry was used to measured physical activity
      over 7 days, the hyperinsulinemic-euglycemic clamp was used to measure insulin
      sensitivity, and DXA was used to measured fat mass. We tested associations of
      physical activity with insulin sensitivity, fat mass, blood pressure, serum lipid
      concentrations, and serum high sensitivity C-reactive protein concentration using
      multivariable linear regression, adjusting for possible confounding factors.
      RESULTS: Participants with CKD were less active than participants without CKD
      (mean (SD) 468.1 (233.1) versus 662.3 (292.5) counts per minute) and had lower
      insulin sensitivity (4.1 (2.1) versus 5.2 (2.0 (mg/min)/(MUU/mL)), higher fat
      mass (32.0 (11.4) versus 29.4 (14.8) kg), and higher triglyceride concentrations
      (153.2 (91.6) versus 99.6 (66.8) mg/dL). With adjustment for demographics,
      comorbidity, medications, and estimated GFR, each two-fold higher level of
      physical activity was associated with a 0.9 (mg/min)/(MUU/mL) higher insulin
      sensitivity (95% CI 0.2, 1.5, p = 0.006), an 8.0 kg lower fat mass (-12.9, -3.1,
      p = 0.001), and a 37.9 mg/dL lower triglyceride concentration (-71.9, -3.9, p =
      0.03). Associations of physical activity with insulin sensitivity and
      triglycerides did not differ significantly by CKD status (p-values for
      interaction >0.3). CONCLUSIONS: Greater physical activity is associated with
      multiple manifestations of metabolic health among people with moderate-severe
      CKD.

PMID- 27876009
TI  - Lifestyle, medication and socio-demographic determinants of mental and physical
      health-related quality of life in people with multiple sclerosis.
AB  - BACKGROUND: Health-related quality of life (QOL) is a key outcome for people with
      multiple sclerosis (MS). While modifiable lifestyle factors, like smoking,
      physical activity and vitamin D, have strong associations with development and
      progression of MS, few studies have examined such associations with QOL. METHODS:
      Using patient-reported data from 2312 people with MS from 54 countries,
      regression models explored associations of socio-demographic, therapeutic and
      lifestyle factors with QOL, using the Multiple Sclerosis Quality of Life-54
      (MSQOL-54). RESULTS: Participants were on average 45.6 years old, 82.4% women,
      mostly partnered (74.1%), with a university degree (59.5%). Controlling for socio
      demographic factors and disability, factors associated with better physical
      health composite (PHC) (on a 100 point scale) were: moderate and high physical
      activity compared to low (5.9 [95% confidence interval: 4.2, 7.6] and 9.9 [CI:
      8.1, 11.6] points higher score respectively); non-smoking compared to current
      smoking (4.6 points [CI: 2.4, 6.7]); better diet (per 10 points on the 100 point
      Diet Habits Questionnaire scale (DHQ) 1.6 points [CI: 1.0, 2.2] points); normal
      body mass index (BMI) versus overweight or obese (2.1 points [CI: 0.4, 3.7] and
      2.4 points [CI: 0.5, 4.3]); fewer comorbidities (4.4 points [CI: 3.9, 4.9]); and
      not taking a disease-modifying drug (DMD) (2.1 points [CI: 0.7, 3.4]). Better
      mental health composite (MHC) determinants were: moderate and high physical
      activity compared to low (4.0 points [CI: 2.0, 6.0] and 5.7 points [CI: 3.5,
      8.0]); non-smoking compared to current (6.7 points [CI: 4.1, 9.3]); better diet
      (2.8 points [CI: 1.9, 3.5]); normal BMI versus overweight or obese (3.1 points
      [CI: 1.1, 5.1] and 3.5 points [CI: 1.3, 5.7]); meditating regularly (2.2 points
      [CI: 0.2, 4.2]); and no DMD use (2.9 points [CI: 1.3, 4.6]). CONCLUSIONS: While
      causality cannot be concluded from cross-sectional data, the associations between
      modifiable lifestyle factors and QOL suggest significant potential for secondary
      prevention of the known deterioration of QOL for people with MS through lifestyle
      risk factor modification.

PMID- 27876010
TI  - A discriminant analysis prediction model of non-syndromic cleft lip with or
      without cleft palate based on risk factors.
AB  - BACKGROUND: A risk prediction model of non-syndromic cleft lip with or without
      cleft palate (NSCL/P) was established by a discriminant analysis to predict the
      individual risk of NSCL/P in pregnant women. METHODS: A hospital-based case
      control study was conducted with 113 cases of NSCL/P and 226 controls without
      NSCL/P. The cases and the controls were obtained from 52 birth defects'
      surveillance hospitals in Hunan Province, China. A questionnaire was administered
      in person to collect the variables relevant to NSCL/P by face to face interviews.
      Logistic regression models were used to analyze the influencing factors of
      NSCL/P, and a stepwise Fisher discriminant analysis was subsequently used to
      construct the prediction model. RESULTS: In the univariate analysis, 13
      influencing factors were related to NSCL/P, of which the following 8 influencing
      factors as predictors determined the discriminant prediction model: family
      income, maternal occupational hazards exposure, premarital medical examination,
      housing renovation, milk/soymilk intake in the first trimester of pregnancy,
      paternal occupational hazards exposure, paternal strong tea drinking, and family
      history of NSCL/P. The model had statistical significance (lambda = 0.772, chi
      square = 86.044, df = 8, P < 0.001). Self-verification showed that 83.8 % of the
      participants were correctly predicted to be NSCL/P cases or controls with a
      sensitivity of 74.3 % and a specificity of 88.5 %. The area under the receiver
      operating characteristic curve (AUC) was 0.846. CONCLUSIONS: The prediction model
      that was established using the risk factors of NSCL/P can be useful for
      predicting the risk of NSCL/P. Further research is needed to improve the model,
      and confirm the validity and reliability of the model.

PMID- 27876011
TI  - Nivolumab-associated acute glomerulonephritis: a case report and literature
      review.
AB  - BACKGROUND: Immune checkpoint inhibitors are changing the landscape of oncology
      treatment as they are significantly improving treatment for multiple
      malignancies. Nivolumab, an anti-programmed death 1 antibody, is a US Food and
      Drug Administration-approved treatment for melanoma, non-small cell lung cancer,
      and kidney cancer but can result in a spectrum of autoimmune side effects.
      Adverse effects can occur within any organ system in the body including the
      colon, lung, liver, endocrine systems, or kidneys. CASE PRESENTATION: A 70-year
      old male with clear cell kidney cancer was admitted with acute kidney injury
      while on nivolumab. A kidney biopsy revealed diffuse tubular injury and immune
      complex-mediated glomerulonephritis. Electron microscopy of the specimen showed
      hump-like subepithelial deposits. Nivolumab was discontinued and the patient was
      started on a high dose of steroids. After 5 months of systemic corticosteroids
      and hemodialysis, the patient's kidney function improved to his baseline level.
      Despite a prolonged interruption to treatment, immunosuppressive therapy did not
      compromise the anticancer effects of nivolumab. CONCLUSION: Immune-related
      adverse effects in the kidney can cause autoimmune glomerulonephritis as well as
      tubulointerstitial injury. In the literature, immune-related nephritis generally
      responded well to systemic corticosteroid treatment. Based on our experience, a
      prolonged course of a high dose of steroids and hemodialysis may be required to
      achieve an adequate treatment effect.

PMID- 27876013
TI  - Reduced neonatal mortality in a regional hospital in Mozambique linked to a
      Quality Improvement intervention.
AB  - BACKGROUND: Neonatal mortality remains a serious health issue especially in low
      resource countries, where 99% of neonatal deaths occur. Doctors with Africa CUAMM
      is an Italian non-governmental organization in the field of healthcare that has
      been working in Africa since 1955. In Mozambique, at the Central Beira Hospital
      (CBH), it has a project with the aim of supporting the neonatal intensive care
      unit (NICU) and the Obstetrical Department of the CBH through a multi-level
      intervention. Our aim was to evaluate the effectiveness of CUAMM continuous
      Quality Improvement intervention in terms of reduction of the overall neonatal
      mortality rate in the NICU of CBH. METHODS: A baseline analysis was performed in
      order to assess the actual standard of neonatal care. Subsequently, the
      intervention was focused on three main areas: infrastructure, equipment and
      clinical protocols improvement. A retrospective pre- (2013)/post- (2014)
      implementation analysis of clinical outcomes was performed. RESULTS: Total
      population included 4,276 newborns, 2,118 (50%) born in 2013 and 2158 (50%) born
      after implementation. Baseline characteristics of the two groups were similar
      apart from a higher incidence of outborn neonates (33% vs 30%, p = 0.02) and a
      lower incidence of Apgar score < 7 at 5 min (37% vs 43%, p < 0.01). The rates of
      admissions for asphyxia (22% vs 30%), sepsis (4% vs 7%) and prematurity (18% vs
      28%) increased between the two study period. Mortality rate for each of these
      causes decreased from before to after the implementation: asphyxia (34% vs 19%, p
      < 0.01), sepsis (39% vs 28%, p = 0.06) and prematurity (43% vs 33%, p < 0.01).
      CONCLUSION: We found a reduction in mortality rate among newborns admitted to
      CBH's NICU after the first year of CUAMM intervention. Most of this reduction can
      be attributed to the decrease in deaths for asphyxia, sepsis and prematurity. A
      Quality Improvement intervention based on infrastructural, equipment and clinical
      objectives was associated with a reduction of neonatal mortality rate in a low
      resource NICU.

PMID- 27876012
TI  - Phase I study of low-dose metronomic temozolomide for recurrent malignant
      gliomas.
AB  - BACKGROUND: The treatment goal for recurrent malignant gliomas centers on disease
      stabilization while minimizing therapy-related side effects. Metronomic dosing of
      cytotoxic chemotherapy has emerged as a promising option to achieve this
      objective. METHODS: This phase I study was performed using metronomic
      temozolomide (mTMZ) at 25 or 50 mg/m2/day continuously in 42-day cycles.
      Correlative studies were incorporated using arterial spin labeling MRI to assess
      tumor blood flow, analysis of matrix metalloproteinase-2 (MMP-2) and MMP-9
      activities in the cerebrospinal fluid (CSF) as surrogates for tumor angiogenesis
      and invasion, as well as determination of CSF soluble interleukin-2 receptor
      alpha (sIL-2Ralpha) levels as a marker of immune modulation. RESULTS: Nine
      subjects were enrolled and toxicity consisted of primarily grade 1 or 2
      hematological and gastrointestinal side effects; only one patient had a grade 3
      elevated liver enzyme level that was reversible. Tumor blood flow was variable
      across subjects and time, with two experiencing a transient increase before a
      decrease to below baseline level while one exhibited a gradual drop in blood flow
      over time. MMP-2 activity correlated with overall survival but not with
      progression free survival, while MMP-9 activity did not correlate with either
      outcome parameters. Baseline CSF sIL-2Ralpha level was inversely correlated with
      time from initial diagnosis to first progression, suggesting that subjects with
      higher sIL-2Ralpha may have more aggressive disease. But they lived longer when
      treated with mTMZ, probably due to drug-related changes in T-cell constituency.
      CONCLUSIONS: mTMZ possesses efficacy against recurrent malignant gliomas by
      altering blood flow, slowing invasion and modulating antitumor immune function.

PMID- 27876014
TI  - Prenatal diagnosis in Sweden 2011 to 2013-a register-based study.
AB  - BACKGROUND: Prenatal diagnosis involves methods used in early pregnancy as either
      screening tests or diagnostic methods. The aims of the study were to i)
      investigate guidelines on prenatal diagnosis in the counties of Sweden, ii)
      investigate uptake of prenatal diagnosis, and iii) background characteristics and
      pregnancy outcomes in relation to different prenatal diagnostic methods. METHODS:
      A retrospective cross-sectional study using data from the Swedish Pregnancy
      Register 2011 to 2013 (284,789 pregnancies) was performed. Additionally,
      guidelines on prenatal diagnosis were collected. Biostatistical and
      epidemiological analyses were performed including calculation of odds ratios (OR)
      and their 95% confidence intervals in univariate and multivariate logistic
      regression analyses. RESULTS: The national uptake of routine ultrasound
      examination, Combined Ultrasound and Biochemical test (CUB), Amniocentesis (AC)
      and Chorionic Villus Sampling (CVS) were 97.6, 33.0, 2.6 and 1.1%, respectively.
      From 2012, 6/21 counties offered CUB test to all pregnant women, nine counties at
      specific indications, and five counties did not offer CUB at all. Advanced
      maternal age demonstrated the highest impact on uptake of prenatal diagnosis.
      Further, university educational level in relation to lower educational level was
      associated with an increased likelihood of undergoing CUB (OR 2.30, 95% CI 2.26
      2.35), AC (OR 1.54, 95% CI 1.46-1.63) and CVS (OR 2.68, 95% CI 2.44-2.93).
      CONCLUSION: Offers of prenatal diagnosis varied considerably between counties
      resulting in unequal access to prenatal diagnosis for pregnant women. The
      intentions of the Swedish Health and Medical Services Act stating equal care for
      all, was thus not fulfilled.

PMID- 27876015
TI  - On normative judgments and ethics.
AB  - Recent rapid technological and medical advance has more than ever before brought
      to the fore a spectrum of problems broadly categorized under the umbrella of
      'ethics of human enhancement'. Some of the most contentious issues are typified
      well by the arguments put forward in a recent article on human cognitive
      enhancement authored by Garasic and Lavazza. Herein I analyse some of the
      assumptions made in their work and highlight important flaws. In particular I
      address the problems associated with the distinction between 'treatment' and
      'enhancement', and 'natural' vs. 'non-natural' therapies.

PMID- 27876016
TI  - Incidence and risk of hypertension in patients newly treated for multiple
      myeloma: a retrospective cohort study.
AB  - BACKGROUND: Hypertension is commonly reported in multiple myeloma (MM) patients
      and may be associated with older age, disease-related complications and
      consequences of MM treatments. This study evaluated the incidence rates of and
      risk factors for hypertension and malignant hypertension in newly-treated MM
      patients in the United States. METHODS: Newly-treated adult MM patients were
      identified from Truven MarketScan claims database from 1/1/05 to 3/31/14.
      Inclusion criteria were new diagnosis of MM with start of MM treatment, >=12
      months continuous enrollment prior to diagnosis, >=30 days of continuous
      enrollment following initial diagnosis, and prescription drug coverage. Non-MM
      patients were matched for age (within +/- 5 years), sex and distribution of index
      dates to MM patients. Baseline cardiovascular (CV) comorbidities, incidence rate
      of hypertension and malignant hypertension in the follow-up period, and risk of
      hypertension and malignant hypertension based on existing baseline CV
      comorbidities were evaluated. RESULTS: A total of 7895 MM patients (38% with
      hypertension history) and 23,685 non-MM patients (24% with hypertension history)
      were included in the study. Twenty-two percent of MM patients versus 3% of non-MM
      patients had baseline renal failure. A higher percentage of MM versus non-MM
      patients had baseline hypertension in combination with renal failure, congestive
      heart failure or both. The incidence rate of hypertension in MM and non-MM
      patients was 260 and 178 per 1000 person-years, respectively. There was a 30%
      increase in the risk of hypertension for MM versus non-MM patients: hazard ratio
      (HR) 1.30 (95% confidence interval [CI] 1.22, 1.37). In MM patients with a
      history of hypertension, the risk of malignant hypertension was significantly
      increased with the following comorbid conditions: cardiomyopathy, HR 2.79 (95% CI
      1.20, 6.48); renal failure, HR 2.13 (95% CI 1.36, 3.34); and diabetes mellitus,
      HR 1.59 (95% CI 1.05, 2.39). CONCLUSIONS: This study confirms that the incidence
      of hypertension and malignant hypertension is significantly higher in newly
      treated MM versus non-MM patients. Hypertension is a risk factor for MM patients
      developing malignant hypertension. Management of CV comorbidities in MM patients
      is important based on the increased risk of hypertension and malignant
      hypertension among patients with these comorbidities.

PMID- 27876018
TI  - Social norms and family planning decisions in South Sudan.
AB  - BACKGROUND: With a maternal mortality ratio of 789 per 100,000 live births, and a
      contraceptive prevalence rate of 4.7%, South Sudan has one of the worst
      reproductive health situations in the world. Understanding the social norms
      around sexuality and reproduction, across different ethnic groups, is key to
      developing and implementing locally appropriate public health responses. METHODS:
      A qualitative study was conducted in the state of Western Bahr el Ghazal (WBeG)
      in South Sudan to explore the social norms shaping decisions about family
      planning among the Fertit community. Data were collected through five focus group
      discussions and 44 semi-structured interviews conducted with purposefully
      selected community members and health personnel. RESULTS: Among the Fertit
      community, the social norm which expects people to have as many children as
      possible remains well established. It is, however, under competitive pressure
      from the existing norm which makes spacing of pregnancies socially desirable.
      Young Fertit women are increasingly, either covertly or overtly, making family
      planning decisions themselves; with resistance from some menfolk, but also
      support from others. The social norm of having as many children as possible is
      also under competitive pressure from the emerging norm that equates taking good
      care of one's children with providing them with a good education. The return of
      peace and stability in South Sudan, and people's aspirations for freedom and a
      better life, is creating opportunities for men and women to challenge and subvert
      existing social norms, including but not limited to those affecting reproductive
      health, for the better. CONCLUSIONS: The sexual and reproductive health
      programmes in WBeG should work with and leverage existing and emerging social
      norms on spacing in their health promotion activities. Campaigns should focus on
      promoting a family ideal in which children become the object of parental
      investment, rather than labour to till the land - instead of focusing directly or
      solely on reducing family size. The conditions are right in WBeG and in South
      Sudan for public health programmes to intervene to trigger social change on
      matters related to sexual and reproductive health; this window of opportunity
      should be leveraged to achieve sustainable change.

PMID- 27876017
TI  - Increased Wnt5a in squamous cell lung carcinoma inhibits endothelial cell
      motility.
AB  - BACKGROUND: Angiogenesis is important both in normal tissue function and disease
      and represents a key target in lung cancer (LC) therapy. Unfortunately, the two
      main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC)
      and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g.
      anti-vascular endothelial growth factor (VEGF)-A treatment with life-threatening
      side effects, often pulmonary hemorrhage in SCC. The mechanisms behind such
      adverse reactions are still largely unknown, although peroxisome proliferator
      activator receptor (PPAR) gamma as well as Wnt-s have been named as molecular
      regulators of the process. As the Wnt microenvironments in NSCLC subtypes are
      drastically different, we hypothesized that the particularly high levels of non
      canonical Wnt5a in SCC might be responsible for alterations in blood vessel
      growth and result in serious adverse reactions. METHODS: PPARgamma, VEGF-A,
      Wnt5a, miR-27b and miR-200b levels were determined in resected adenocarcinoma and
      squamous cell carcinoma samples by qRT-PCR and TaqMan microRNA assay. The role of
      PPARgamma in VEGF-A expression, and the role of Wnts in overall regulation was
      investigated using PPARgamma knock-out mice, cancer cell lines and fully human,
      in vitro 3 dimensional (3D), distal lung tissue aggregates. PPARgamma mRNA and
      protein levels were tested by qRT-PCR and immunohistochemistry, respectively.
      PPARgamma activity was measured by a PPRE reporter system. The tissue engineered
      lung tissues expressing basal level and lentivirally delivered VEGF-A were
      treated with recombinant Wnts, chemical Wnt pathway modifiers, and were subjected
      to PPARgamma agonist and antagonist treatment. RESULTS: PPARgamma down-regulation
      and VEGF-A up-regulation are characteristic to both AC and SCC. Increased VEGF-A
      levels are under direct control of PPARgamma. PPARgamma levels and activity,
      however, are under Wnt control. Imbalance of both canonical (in AC) and non
      canonical (in SCC) Wnts leads to PPARgamma down-regulation. While canonical Wnts
      down-regulate PPARgamma directly, non-canonical Wnt5a increases miR27b that is
      known regulator of PPARgamma. CONCLUSION: During carcinogenesis the Wnt
      microenvironment alters, which can downregulate PPARgamma leading to increased
      VEGF-A expression. Differences in the Wnt microenvironment in AC and SCC of NSCLC
      lead to PPARgamma decrease via mechanisms that differentially alter endothelial
      cell motility and branching which in turn can influence therapeutic response.

PMID- 27876020
TI  - The brief negative symptom scale: validation of the German translation and
      convergent validity with self-rated anhedonia and observer-rated apathy.
AB  - BACKGROUND: Negative symptoms are considered core symptoms of schizophrenia. The
      Brief Negative Symptom Scale (BNSS) was developed to measure this symptomatic
      dimension according to a current consensus definition. The present study examined
      the psychometric properties of the German version of the BNSS. To expand former
      findings on convergent validity, we employed the Temporal Experience Pleasure
      Scale (TEPS), a hedonic self-report that distinguishes between consummatory and
      anticipatory pleasure. Additionally, we addressed convergent validity with
      observer-rated assessment of apathy with the Apathy Evaluation Scale (AES), which
      was completed by the patient's primary nurse. METHODS: Data were collected from
      75 in- and outpatients from the Psychiatric Hospital, University Zurich diagnosed
      with either schizophrenia or schizoaffective disorder. We assessed convergent and
      discriminant validity, internal consistency and inter-rater reliability. RESULTS:
      We largely replicated the findings of the original version showing good
      psychometric properties of the BNSS. In addition, the primary nurses evaluation
      correlated moderately with interview-based clinician rating. BNSS anhedonia items
      showed good convergent validity with the TEPS. CONCLUSIONS: Overall, the German
      BNSS shows good psychometric properties comparable to the original English
      version. Convergent validity extends beyond interview-based assessments of
      negative symptoms to self-rated anhedonia and observer-rated apathy.

PMID- 27876019
TI  - A systematic comparison of copy number alterations in four types of female
      cancer.
AB  - BACKGROUND: Detection and localization of genomic alterations and breakpoints are
      crucial in cancer research. The purpose of this study was to investigate, in a
      methodological and biological perspective, different female, hormone-dependent
      cancers to identify common and diverse DNA aberrations, genes, and pathways.
      METHODS: In this work, we analyzed tissue samples from patients with breast (n =
      112), ovarian (n = 74), endometrial (n = 84), or cervical (n = 76) cancer. To
      identify genomic aberrations, the Circular Binary Segmentation (CBS) and
      Piecewise Constant Fitting (PCF) algorithms were used and segmentation thresholds
      optimized. The Genomic Identification of Significant Targets in Cancer (GISTIC)
      algorithm was applied to the segmented data to identify significantly altered
      regions and the associated genes were analyzed by Ingenuity Pathway Analysis
      (IPA) to detect over-represented pathways and functions within the identified
      gene sets. RESULTS AND DISCUSSION: Analyses of high-resolution copy number
      alterations in four different female cancer types are presented. For
      appropriately adjusted segmentation parameters the two segmentation algorithms
      CBS and PCF performed similarly. We identified one region at 8q24.3 with focal
      aberrations that was altered at significant frequency across all four cancer
      types. Considering both, broad regions and focal peaks, three additional regions
      with gains at significant frequency were revealed at 1p21.1, 8p22, and 13q21.33,
      respectively. Several of these events involve known cancer-related genes, like
      PPP2R2A, PSCA, PTP4A3, and PTK2. In the female reproductive system (ovarian,
      endometrial, and cervix [OEC]), we discovered three common events: copy number
      gains at 5p15.33 and 15q11.2, further a copy number loss at 8p21.2.
      Interestingly, as many as 75% of the aberrations (75% amplifications and 86%
      deletions) identified by GISTIC were specific for just one cancer type and
      represented distinct molecular pathways. CONCLUSIONS: Our results disclose that
      some prominent copy number changes are shared in the four examined female,
      hormone-dependent cancer whereas others are definitive to specific cancer types.

PMID- 27876021
TI  - Epidemiology of pertussis in two Ibero-American countries with different
      vaccination policies: lessons derived from different surveillance systems.
AB  - BACKGROUND: Pertussis is a re-emerging disease worldwide despite its high
      vaccination coverage. European and Latin-American countries have used different
      surveillance and vaccination policies against pertussis. We compared the
      epidemiology of this disease in two Ibero-American countries with different
      vaccination and surveillance policies. METHODS: We compared the epidemiology of
      pertussis in Spain and the Dominican Republic (DR). We present a 10-year
      observational study of reported pertussis based on suspected and/or probable
      cases of pertussis identified by the national mandatory reporting system in both
      countries between 2005 and 2014. Both countries have a similar case definition
      for pertussis surveillance, although Spain applies laboratory testing, and uses
      real time PCR and/or culture for case confirmation while in DR only probable
      and/or suspected cases are reported. We analyzed incidence, hospitalization, case
      fatality rates, mortality and vaccination coverage. RESULTS: The average annual
      incidence in children aged <1 year was 3.40/100,000 population in Spain and
      12.15/100,000 in DR (p = 0.01). While the incidence in DR was generally higher
      than in Spain, in 2011 it was six times higher in Spain than in DR. The highest
      infant mortality in Spain was 0.017/100,000 in 2011, and the highest in DR was
      0.08/100,000 in 2014 (p = 0.01). The proportion of hospitalized cases per year
      among children <1 year varied between 22.0% and 93.7% in Spain, and between 1.1%
      and 29.4% in DR (p = 0.0002), while mortality varied from 0 to 0.017 and 0 to
      0.08 per 100,000 population in Spain and DR, respectively (p = 0.001).
      Vaccination coverage was 96.5% in Spain and 82.2% in DR (p = 0.001). CONCLUSIONS:
      Pertussis is a public health problem in both countries. Surveillance, prevention
      and control measures should be improved, especially in DR. Current vaccination
      programs are not sufficient for preventing continued pertussis transmission, even
      in Spain which has high vaccination coverage.

PMID- 27876022
TI  - Foot insensitivity is associated with renal function decline in patients with
      type 2 diabetes: a cohort study.
AB  - BACKGROUND: Identifying patients with diabetes at increased risk of chronic
      kidney disease (CKD) is essential to prevent/slow the progression to end-stage
      renal disease (ESRD). CKD and diabetic peripheral neuropathy (DPN) share common
      mechanisms. Hence, we aimed to examine the relationship between foot
      insensitivity and CKD in patients with Type 2 diabetes. METHODS: A prospective
      observational cohort study in adults with Type 2 diabetes. Patients with ESRD
      were excluded. Foot insensitivity was assessed using the 10-g monofilament test.
      Renal function was assessed using estimated glomerular filtration rate (eGFR)
      based on the MDRD equation. Albuminuria was defined as the presence of urinary
      albumin/creatinine ratio (ACR) >3.4 mg/mmol. RESULTS: Two hundred and twenty
      eight patients were recruited and followed-up for 2.5 years. One hundred and
      ninety patients (83.4%) had eGFR >= 60 ml/min/1.73 m2. Seventy six (33.3%)
      patients had foot insensitivity (i.e. abnormal monofilament test). Patients with
      foot insensitivity had lower eGFR and higher prevalence of albuminuria compared
      to patients with normal monofilament test. After adjustment for age, gender,
      ethnicity, diabetes duration, HbA1c, body mass index, insulin treatment, number
      of anti-hypertensives, history of peripheral vascular disease, and baseline eGFR
      (R2 0.87), baseline foot insensitivity was associated with study-end eGFR (B = 
      3.551, p = 0.036). CONCLUSIONS: Patients with Type 2 diabetes and foot
      insensitivity are at increased risk of eGFR decline. Identifying these patients
      offers an opportunity to intensify metabolic and blood pressure control to
      prevent/retard the development of CKD. Future studies of larger sample size and
      longer follow up from multiple centres are needed to assess the diagnostic
      performance of our findings in predicting CKD development, and to compare the
      performance of the monofilament test with albuminuria.

PMID- 27876023
TI  - Association of parental social support with energy balance-related behaviors in
      low-income and ethnically diverse children: a cross-sectional study.
AB  - BACKGROUND: Parents play an important role in providing their children with
      social support for healthy eating and physical activity. However, different types
      of social support (e.g., instrumental, emotional, modeling, rules) might have
      different results on children's actual behavior. The purpose of this study was to
      assess the association of the different types of social support with children's
      physical activity and eating behaviors, as well as to examine whether these
      associations differ across racial/ethnic groups. METHODS: We surveyed 1169 low
      income, ethnically diverse third graders and their caregivers to assess how
      children's physical activity and eating behaviors (fruit and vegetable and sugar
      sweetened beverage intake) were associated with instrumental social support,
      emotional social support, modeling, rules and availability of certain foods in
      the home. We used sequential linear regression to test the association of
      parental social support with a child's physical activity and eating behaviors,
      adjusting for covariates, and then stratified to assess the differences in this
      association between racial/ethnic groups. RESULTS: Parental social support and
      covariates explained 9-13% of the variance in children's energy balance-related
      behaviors. Family food culture was significantly associated with fruit and
      vegetable and sugar-sweetened beverage intake, with availability of sugar
      sweetened beverages in the home also associated with sugar-sweetened beverage
      intake. Instrumental and emotional support for physical activity were
      significantly associated with the child's physical activity. Results indicate
      that the association of various types of social support with children's physical
      activity and eating behaviors differ across racial/ethnic groups. CONCLUSIONS:
      These results provide considerations for future interventions that aim to enhance
      parental support to improve children's energy balance-related behaviors.

PMID- 27876025
TI  - Substituting sugar confectionery with fruit and healthy snacks at checkout - a
      win-win strategy for consumers and food stores? a study on consumer attitudes and
      sales effects of a healthy supermarket intervention.
AB  - BACKGROUND: The widespread use of in-store marketing strategies to induce
      unhealthy impulsive purchases has implications for shopping experience, food
      choice and possibly adverse health outcomes. The aim of this study was to examine
      consumer attitudes and evaluate sales effects of a healthy checkout supermarket
      intervention. The study was part of Project Sundhed & Lokalsamfund (Project SoL);
      a Danish participatory community-based health promotion intervention. METHODS:
      Consumer attitudes towards unhealthy snack exposure in supermarkets were examined
      in a qualitative pre-intervention study (29 short in-store interviews, 11 semi
      structured interviews and three focus group interviews). Findings were presented
      to food retailers and informed the decision to test a healthy checkout
      intervention. Sugar confectionery at one checkout counter was substituted with
      fruit and healthy snacking items in four stores for 4 weeks. The intervention was
      evaluated by 48 short exit interviews on consumer perceptions of the intervention
      and by linear mixed model analyses of supermarket sales data from the
      intervention area and a matched control area. RESULTS: The qualitative pre
      intervention study identified consumer concern and annoyance with placement and
      promotion of unhealthy snacks in local stores. Store managers were willing to
      respond to local consumer concern and a healthy checkout intervention was
      therefore implemented. Exit interviews found positive attitudes towards the
      intervention, while intervention awareness was modest. Most participants believed
      that the intervention could help other consumers make healthier choices, while
      fewer expected to be influenced by the intervention themselves. Statistical
      analyses suggested an intervention effect on sales of carrot snack packs when
      compared with sales before the intervention in Bornholm control stores (P <
      0.05). No significant intervention effect on sales of other intervention items or
      sugar confectionery was found. CONCLUSIONS: The present study finds that the
      healthy checkout intervention was positively evaluated by consumers and provided
      a 'responsible' branding opportunity for supermarkets, thus representing a win
      win strategy for store managers and consumers in the short term. However, the
      intervention was too modest to draw conclusions on long-term sales and health
      implications of this initiative. More research is needed to assess whether
      retailer-researcher collaborations on health promotion can be a winning strategy
      for public health.

PMID- 27876024
TI  - Evaluation of computer-based computer tomography stratification against outcome
      models in connective tissue disease-related interstitial lung disease: a patient
      outcome study.
AB  - BACKGROUND: To evaluate computer-based computer tomography (CT) analysis
      (CALIPER) against visual CT scoring and pulmonary function tests (PFTs) when
      predicting mortality in patients with connective tissue disease-related
      interstitial lung disease (CTD-ILD). To identify outcome differences between
      distinct CTD-ILD groups derived following automated stratification of CALIPER
      variables. METHODS: A total of 203 consecutive patients with assorted CTD-ILDs
      had CT parenchymal patterns evaluated by CALIPER and visual CT scoring:
      honeycombing, reticular pattern, ground glass opacities, pulmonary vessel volume,
      emphysema, and traction bronchiectasis. CT scores were evaluated against
      pulmonary function tests: forced vital capacity, diffusing capacity for carbon
      monoxide, carbon monoxide transfer coefficient, and composite physiologic index
      for mortality analysis. Automated stratification of CALIPER-CT variables was
      evaluated in place of and alongside forced vital capacity and diffusing capacity
      for carbon monoxide in the ILD gender, age physiology (ILD-GAP) model using
      receiver operating characteristic curve analysis. RESULTS: Cox regression
      analyses identified four independent predictors of mortality: patient age (P <
      0.0001), smoking history (P = 0.0003), carbon monoxide transfer coefficient (P =
      0.003), and pulmonary vessel volume (P < 0.0001). Automated stratification of
      CALIPER variables identified three morphologically distinct groups which were
      stronger predictors of mortality than all CT and functional indices. The
      Stratified-CT model substituted automated stratified groups for functional
      indices in the ILD-GAP model and maintained model strength (area under curve
      (AUC) = 0.74, P < 0.0001), ILD-GAP (AUC = 0.72, P < 0.0001). Combining automated
      stratified groups with the ILD-GAP model (stratified CT-GAP model) strengthened
      predictions of 1- and 2-year mortality: ILD-GAP (AUC = 0.87 and 0.86,
      respectively); stratified CT-GAP (AUC = 0.89 and 0.88, respectively).
      CONCLUSIONS: CALIPER-derived pulmonary vessel volume is an independent predictor
      of mortality across all CTD-ILD patients. Furthermore, automated stratification
      of CALIPER CT variables represents a novel method of prognostication at least as
      robust as PFTs in CTD-ILD patients.

PMID- 27876026
TI  - Spatial suicide clusters in Australia between 2010 and 2012: a comparison of
      cluster and non-cluster among young people and adults.
AB  - BACKGROUND: A suicide cluster has been defined as a group of suicides that occur
      closer together in time and space than would normally be expected. We aimed to
      examine the extent to which suicide clusters exist among young people and adults
      in Australia and to determine whether differences exist between cluster and non
      cluster suicides. METHODS: Suicide data were obtained from the National Coronial
      Information System for the period 2010 and 2012. Data on date of death, postcode,
      age at the time of death, sex, suicide method, ICD-10 code for cause of death,
      marital status, employment status, and aboriginality were retrieved. We examined
      the presence of spatial clusters separately for youth suicides and adult suicides
      using the Scan statistic. Pearson's chi-square was used to compare the
      characteristics of cluster suicides with non-cluster suicides. RESULTS: We
      identified 12 spatial clusters between 2010 and 2012. Five occurred among young
      people (n = 53, representing 5.6% [53/940] of youth suicides) and seven occurred
      among adults (n = 137, representing 2.3% [137/5939] of adult suicides). Clusters
      ranged in size from three to 21 for youth and from three to 31 for adults. When
      compared to adults, suicides by young people were significantly more likely to
      occur as part of a cluster (difference = 3.3%, 95% confidence interval [CI] = 1.8
      to 4.8, p < 0.0001). Suicides by people with an Indigenous background were also
      significantly more likely to occur in a cluster than suicide by non-Indigenous
      people and this was the case among both young people and adults. CONCLUSIONS:
      Suicide clusters have a significant negative impact on the communities in which
      they occur. As a result it is important to find effective ways of managing and
      containing suicide clusters. To date there is limited evidence for the
      effectiveness of those strategies typically employed, in particular in Indigenous
      settings, and developing this evidence base needs to be a future priority. Future
      research that examines in more depth the socio-demographic and clinical factors
      associated with suicide clusters is also warranted in order that appropriate
      interventions can be developed.

PMID- 27876027
TI  - Application of the multiphase optimization strategy to a pilot study: an
      empirical example targeting obesity among children of low-income mothers.
AB  - BACKGROUND: Emerging approaches to building more efficient and effective
      behavioral interventions are becoming more widely available. The current paper
      provides an empirical example of the use of the engineering-inspired multiphase
      optimization strategy (MOST) to build a remotely delivered responsive parenting
      intervention to prevent obesity among children of low-income mothers with and
      without depressive symptoms. METHODS: Participants were 107 mothers with (n = 45)
      and without (n = 62) depressive symptoms who had a child aged 12 to 42 months
      participating in the Women, Infants and Children program. Participants were
      randomized to one of sixteen experimental conditions using a factorial design
      that included a combination of the following eight remotely delivered
      intervention components: responsive feeding curriculum (given to all
      participants), parenting curriculum, portion size guidance, obesogenic risk
      assessment, personalized feedback on mealtime routines, feeding curriculum
      counseling, goal setting, mobile messaging, and social support. This design
      enabled efficient identification of components with low feasibility and
      acceptability. RESULTS: Completion rates were high (85%) and did not
      statistically differ by depressive symptoms. However, mothers with depressive
      symptoms who received obesogenic risk assessment and personalized feedback on
      mealtime routines components had lower completion rates than mothers without
      depressive symptoms. All intervention components were feasible to implement
      except the social support component. Regardless of experimental condition, most
      participants reported that the program increased their awareness of what, when,
      and how to feed their children. CONCLUSIONS: MOST provided an efficient way to
      assess the feasibility of components prior to testing them with a fully powered
      experiment. This framework helped identify potentially challenging combinations
      of remotely delivered intervention components. Consideration of how these results
      can inform future studies focused on the optimization phase of MOST is discussed.

PMID- 27876028
TI  - Clinical assessment of children with renal abscesses presenting to the pediatric
      emergency department.
AB  - BACKGROUND: Renal abscesses are relatively uncommon in children but may result in
      prolonged hospital stays and life-threatening events. We undertook this study to
      analyze the clinical spectrum of renal abscesses in children admitted to the
      pediatric emergency department (ED) and to find helpful clinical characteristics
      that can potentially aid emergency physicians for detecting renal abscesses in
      children earlier. METHODS: From 2004 to 2011, we retrospectively analyzed 17
      patients, aged 18 years or younger, with a definite diagnosis of renal abscess
      admitted to the ED. The following clinical information was studied: demographics,
      clinical presentation, laboratory testing, microbiology, imaging studies,
      treatment modalities, complications, and long-term outcomes. We analyzed these
      variables among other potential predisposing factors. RESULTS: During the 8-year
      study period, 17 patients (7 males and 10 females; mean age, 6.1 +/- 4.5 years)
      were diagnosed with renal abscesses on the basis of ultrasonography and computed
      tomography findings. The 2 most common presenting symptoms were fever and flank
      pain (100% and 70.6%, respectively). All of the patients presented with
      leukocytosis and elevated C-reactive protein (CRP) levels. Organisms cultured
      from urine or from the abscess were identified in 11 (64.7%) patients, and
      Escherichia coli was the most common organism cultured. All patients were treated
      with broad-spectrum intravenous antibiotics with the exception of 4 children who
      also required additional percutaneous drainage of the abscess. CONCLUSIONS: Renal
      abscesses are relatively rare in children. We suggest that primary care
      physicians should keep this disease in mind especially when children present with
      triad symptoms (fever, nausea/vomiting, and flank pain), pyuria, significant
      leukocytosis, and elevated CRP levels. However, aggressive percutaneous drainage
      may not need to be routinely performed in children with renal abscesses.

PMID- 27876029
TI  - Home telemonitoring for patients with acute exacerbation of chronic obstructive
      pulmonary disease: a randomized controlled trial.
AB  - BACKGROUND: Although a number of studies have suggested that the use of
      Telemonitoring (TM) in patients with Chronic Obstructive Pulmonary Disease (COPD)
      can be useful and efficacious, its real utility in detecting Acute Exacerbation
      (AE) signaling the need for prompt treatment is not entirely clear. The current
      study aimed to investigate the benefits of a TM system in managing AE in advanced
      stage COPD patients to improve their Health-Related Quality of Life (HRQL) and to
      reduce utilization of healthcare services. METHODS: A 12-month Randomised
      Controlled Trial (RCT) was conducted in the Veneto region (Italy). Adult patients
      diagnosed with Class III-IV COPD in accordance with the Global Initiative for
      Chronic Obstructive Lung Disease (GOLD) classification were recruited and
      provided a TM system to alert the clinical staff via a trained operator whenever
      variations in respiratory parameters fell beyond the individual's normal range.
      The study's primary endpoint was HRQL, measured by the Italian version of the two
      Short Form 36-item Health Survey (SF36v2). Its secondary endpoints were: scores
      on the Hospital Anxiety and Depression Scale (HADS); the number and duration of
      hospitalizations; the number of readmissions; the number of appointments with a
      pulmonary specialist; the number of visits to the emergency department; and the
      number of deaths. RESULTS: Three hundred thirty-four patients were enrolled and
      randomized into two groups for a 1 year period. At its conclusion, changes in the
      SF36 Physical and Mental Component Summary scores did not significantly differ
      between the TM and control groups [(-2.07 (8.98) vs -1.91 (7.75); p = 0.889 and 
      1.08 (11.30) vs -1.92 (10.92); p = 0.5754, respectively]. Variations in HADS were
      not significantly different between the two groups [0.85 (3.68) vs 0.62 (3.6); p
      = 0.65 and 0.50 (4.3) vs 0.72 (4.5); p = 0.71]. The hospitalization rate for
      AECOPD and/or for any cause was not significantly different in the two groups
      [IRR = 0.89 (95% CI 0.79-1,04); p = 0.16 and IRR = 0.91 (95% CI 0,75 - 1.04); p =
      0.16, respectively]. The readmission rate for AECOPD and/or any cause was,
      however, significantly lower in the TM group with respect to the control one [IRR
      = 0.43 (95% CI 0.19-0.98); p = 0.01 and 0.46 (95% CI 0.24-0.89); p = 0.01,
      respectively]. CONCLUSION: Study results showed that in areas where medical
      services are well established, TM does not significantly improve HRQL in patients
      with COPD who develop AE. Although not effective in reducing hospitalizations, TM
      can nevertheless facilitate continuity of care during hospital-to-home transition
      by reducing the need for early readmission. TRIAL REGISTRATION: Retrospectively
      registered on January 2012, ClinicalTrials.gov Identifier: NCT01513980 .

PMID- 27876031
TI  - User satisfaction with the structure and content of the NEXit intervention, a
      text messaging-based smoking cessation programme.
AB  - BACKGROUND: Smoking is still the leading cause of preventable ill health and
      death. There is a limited amount of evidence for effective smoking cessation
      interventions among young people. To address this, a text messaging-based smoking
      cessation programme, the NEXit intervention, was developed. Short-term
      effectiveness, measured immediately after the 12-week intervention revealed that
      26% of smokers in the intervention group had prolonged abstinence compared with
      15% in the control group. The present study was performed to explore the users'
      experiences of the structure and content of the intervention in order to further
      develop the intervention. METHODS: Students participating in the main NEXit
      randomized controlled trial were invited to grade their experiences of the
      structure and content of the intervention after having completed follow-up. The
      participants received an e-mail with an electronic link to a short questionnaire.
      Descriptive analysis of the distribution of the responses to the questionnaire
      was performed. Free-text comments to 14 questions were analysed. RESULTS: The
      response rate for the user feedback questionnaire was 35% (n = 289/827) and 428
      free-text comments were collected. The first motivational phase of the
      intervention was appreciated by 55% (158/289) of the participants. Most
      participants wanted to quit smoking immediately and only 124/289 (43%) agreed to
      have to decide a quit-date in the future. Most participants 199/289 (69%) found
      the content of the messages in the core programme to be very good or good, and
      the variability between content types was appreciated by 78% (224/289). Only 34%
      (97/289) of the participants thought that all or nearly all messages were
      valuable, and some mentioned that it was not really the content that mattered,
      but that the messages served as a reminder about the decision to quit smoking.
      CONCLUSIONS: The programme was largely perceived satisfactory in most aspects
      concerning structure and content by young people and most participants stated
      that they would recommend it to a friend who wants to quit smoking. The
      motivational phase might be worth shortening and the number of messages around
      the quit date itself reduced. Shorter messages seemed to be more acceptable.
      TRIAL REGISTRATION: ISRCTN75766527 .

PMID- 27876030
TI  - Long-term outcomes following lower extremity press-fit bone-anchored prosthesis
      surgery: a 5-year longitudinal study protocol.
AB  - BACKGROUND: Patients with lower extremity amputation frequently suffer from
      socket-related problems. This seriously limits prosthesis use, level of activity
      and health-related quality of life (HRQoL). An additional problem in patients
      with lower extremity amputation are asymmetries in gait kinematics possibly
      accounting for back pain. Bone-anchored prostheses (BAPs) are a possible solution
      for socket-related problems. Knowledge concerning the level of function, activity
      and HRQoL after surgery is limited. The aims of this ongoing study are to: a)
      describe changes in the level of function, activity, HRQoL and satisfaction over
      time compared to baseline before surgery; b) examine potential predictors for
      changes in kinematics, prosthetic use, walking ability, HRQoL, prosthesis comfort
      over time and level of stump pain at follow-up; c) examine potential mechanisms
      for change of back pain over time by identifying determinants, moderators and
      mediators. METHODS/DESIGN: A prospective 5-year longitudinal study with multiple
      follow-ups. All adults, between May 2014 and May 2018, with lower extremity
      amputation receiving a press-fit BAP are enrolled consecutively. Patients with
      socket-related problems and trauma, tumour resection or stable vascular disease
      as cause of primary amputation will be included. Exclusion criteria are severe
      cognitive or psychiatric disorders. Follow-ups are planned at six-months, one-,
      two- and five-years after BAP surgery. The main study outcomes follow, in part,
      the ICF classification: a) level of function defined as kinematics in coronal
      plane, hip abductor strength, prosthetic use, back pain and stump pain; b) level
      of activity defined as mobility level and walking ability; c) HRQoL; d)
      satisfaction defined as prosthesis comfort and global perceived effect. Changes
      over time for the continuous outcomes and the dichotomized outcome (back pain)
      will be analysed using generalised estimating equations (GEE). Multivariate GEE
      will be used to identify potential predictors for change of coronal plane
      kinematics, prosthetic use, walking ability, HRQoL, prosthesis comfort and for
      the level of post-operative stump pain. Finally, potential mechanisms for change
      in back pain frequency will be explored using coronal plane kinematics as a
      potential determinant, stump pain as moderator and hip abductor strength as
      mediator. DISCUSSION: This study may identify predictors for clinically relevant
      outcome measures. TRIAL REGISTRATION: NTR5776 . Registered 11 March 2016,
      retrospectively registered.

PMID- 27876032
TI  - Self-control and problematic mobile phone use in Chinese college students: the
      mediating role of mobile phone use patterns.
AB  - BACKGROUND: With the popularity of mobile phones, problematic mobile phone use is
      getting increasing attention in recent years. Although self-control was found to
      be a critical predictor of problematic mobile phone use, no study has ever
      explored the association between self-control and mobile phone use patterns as
      well as the possible pathway how self-control affects problematic mobile phone
      use. METHODS: Four hundred sixty-eight college students were randomly selected in
      this study. Data were collected using the Problematic Mobile Phone Use Scale, the
      Self-Control Scale, and the Mobile Phone Use Pattern Questionnaire. Statistical
      tests were conducted to identify the potential role of mobile phone use patterns
      in the association between self-control and problematic mobile phone use.
      RESULTS: In this sample, female students displayed significant higher mobile
      phone dependence than males. Self-control was negatively correlated with
      interpersonal, transaction and entertainment mobile phone use patterns, but
      positively correlated with information seeking use pattern. Self-control could
      predict problematic mobile phone use directly and indirectly via interpersonal
      and transaction patterns. CONCLUSIONS: Our research provided additional evidence
      for the negative association between self-control and problematic mobile phone
      use. Moreover, interpersonal and transaction use patterns played a mediating role
      in this link.

PMID- 27876033
TI  - Genital examination training: assessing the effectiveness of an integrated female
      and male teaching programme.
AB  - BACKGROUND: Learning to undertake intimate female and male examinations is an
      important part of medical student training but opportunities to participate in
      practical, supervised learning in a safe environment can be limited. A
      collaborative, integrated training programme to provide such learning was
      developed by two university teaching departments and a specialist sexual health
      service, utilising teaching associates trained for intimate examinations in a
      simulated clinical educational setting. The objective of this research was to
      determine changes in senior medical students' self- reported experience and
      confidence in performing male and female genital examinations, before and after
      participating in a new clinical teaching programme. METHODS: A quasi-experimental
      mixed methods design, using pre and post programme questionnaires and focus
      groups, was used to assess the effectiveness of the programme. RESULTS: The
      students reported greatly improved skill, confidence and comfort levels for both
      male and female genital examination following the teaching programme. Skill,
      confidence and comfort regarding male examinations were rated particularly low on
      the pre-teaching programme self- assessment, but post-programme was rated at
      similar levels to the female examination. CONCLUSIONS: This integrated female
      male teaching programme (utilising trained teaching associates as simulated
      patients in a supervised clinical teaching environment) was successful in
      increasing senior medical students' skills and levels of confidence in performing
      genital examinations. There were differences between female and male medical
      students in their learning. Suggestions for improvement included providing more
      detailed instruction to some clinical supervisors about their facilitation role
      in the session.

PMID- 27876034
TI  - H5N2 Highly Pathogenic Avian Influenza Viruses from the US 2014-2015 outbreak
      have an unusually long pre-clinical period in turkeys.
AB  - BACKGROUND: From December 2014 through June 2015, the US experienced the most
      costly highly pathogenic avian influenza (HPAI) outbreak to date. Most cases in
      commercial poultry were caused by an H5N2 strain which was a reassortant with 5
      Eurasian lineage genes, including a clade 2.3.4.4 goose/Guangdong/1996 lineage
      hemagglutinin, and 3 genes from North American wild waterfowl low pathogenicity
      avian influenza viruses. The outbreak primarily affected turkeys and table-egg
      layer type chickens. Three isolates were selected for characterization in
      turkeys: the US index isolate from December 2014 (A/northern
      pintail/WA/40964/2014), and two poultry isolates from April 2015
      (A/chicken/IA/13388/2015 and A/turkey/MN/12528/2015). RESULTS: Four week old
      broad-breasted white turkeys were inoculated with one of three doses (102, 104 or
      106 50% egg infectious doses [EID50] per bird) of each of the isolates to
      evaluate infectious dose and pathogenesis. The mean bird infectious dose of
      A/northern pintail/WA/40964/2014 and A/turkey/MN/12528/2015 was 105 EID50 per
      bird, but was 103 EID50 per bird for A/chicken/IA/13388/2015, suggesting the
      latter had greater adaptation to gallinaceous birds. All three isolates had
      unusually long mean death time of 5.3-5.9 days post challenge, and the primary
      clinical signs were severe lethargy and neurological signs which started no more
      than 24 h before death (the average pre-clinical period was 4 days). Infected
      turkeys also shed high levels of virus by both the oropharyngeal and cloacal
      routes. CONCLUSIONS: The unusually long mean death times, high levels of virus in
      feces, and increased adaptation of the later viruses may have contributed to the
      rapid spread of the virus during the peak of the outbreak.

PMID- 27876035
TI  - Study Protocol: Evaluation of a DVD intervention designed to meet the informaton
      needs of patients with head and neck cancer and their partner, carer and
      families.
AB  - BACKGROUND: Patients who undergo surgery for cancer of the head and neck and
      their families face complex and difficult challenges and are at risk of anxiety
      and depression and inability to cope with symptom and treatment burden.
      Information available to support them is not flexible enough to adjust to
      individual need. DESIGN/METHODS: A randomised clinical trial pre and post
      intervention design, comparing the use of a tailored DVD intervention, provided
      preoperatively and used throughout the post- operative period, with usual
      treatment. One hundred fifty-six individuals or partner couples will be randomly
      recruited into either the intervention or control group. A survey will be
      administered at three time points, preoperatively, post operatively and 3 months
      post-surgery. Anxiety and empowerment are the primary outcome measures.
      Qualitative data about use of the resource will be gathered by phone interview.
      DISCUSSION: This is the first study to rigorously evaluate the impact of a DVD
      intervention for this group of patients and their family members. The study will
      help to understand the impact of information usage on patient and family well-
      being and test a means by which to evaluate information and education resources
      for this and other cancer patient groups. TRIAL REGISTRATION: ACTRN12614001104640
      . Date registered: 17/10/2014.

PMID- 27876036
TI  - Diabetes screening intervals based on risk stratification.
AB  - BACKGROUND: Guidelines for frequency of Type 2 diabetes mellitus (DM) screening
      remain unclear, with proposed screening intervals typically based on expert
      opinion. This study aims to demonstrate that HbA1c screening intervals may differ
      substantially when considering individual risk for diabetes. METHODS: This was a
      multi-institutional retrospective open cohort study. Data were collected between
      April 1999 to March 2014 from one urban and one rural cohort in Japan. After
      categorization by age, we stratified individuals based on cardiovascular disease
      risk (Framingham 10-year cardiovascular risk score) and body mass index (BMI). We
      adapted a signal-to-noise method for distinguishing true HbA1c change from
      measurement error by constructing a linear random effect model to calculate
      signal and noise of HbA1c. Screening interval for HbA1c was defined as
      informative when the signal-to-noise ratio exceeded 1. RESULTS: Among 96,456
      healthy adults, 46,284 (48.0%) were male; age (range) and mean HbA1c (SD) were 48
      (30-74) years old and 5.4 (0.4)%, respectively. As risk increased among those 30
      44 years old, HbA1c screening intervals for detecting Type 2 DM consistently
      decreased: from 10.5 (BMI <18.5) to 2.4 (BMI > 30) years, and from 8.0
      (Framingham Risk Score <10%) to 2.0 (Framingham Risk Score >=20%) years. This
      trend was consistent in other age and risk groups as well; among obese 30-44 year
      olds, we found substantially shorter intervals compared to other groups.
      CONCLUSION: HbA1c screening intervals for identification of DM vary substantially
      by risk factors. Risk stratification should be applied when deciding an optimal
      HbA1c screening interval in the general population to minimize overdiagnosis and
      overtreatment.

PMID- 27876037
TI  - The efficacy of adalimumab in psoriatic arthritis concomitant to overlapping
      primary biliary cholangitis and primary sclerosing cholangitis: a case report.
AB  - BACKGROUND: The overlap syndrome of primary biliary cholangitis (formerly called
      primary biliary cirrhosis) and primary sclerosing cholangitis is an extremely
      rare condition that has never been described in association with other immune
      mediated diseases, including psoriatic arthritis. While treatment with anti
      Tumour Necrosis Factor-alpha (TNF-alpha) agents has proved to be effective in
      inflammatory arthropathies such as psoriatic arthritis, they have been employed
      in only a limited number of patients with autoimmune hepatitis, and their
      effectiveness is unclear. CASE PRESENTATION: We report the case of a 51-year-old
      female affected with psoriatic arthritis concomitant to overlapping primary
      biliary cholangitis and primary sclerosing cholangitis in whom 28 months of
      adalimumab treatment improved the symptoms of the inflammatory arthropathy as
      well as those of both cholangiopathies. CONCLUSION: Our results suggest that
      further studies examining the therapeutic role of this particular TNF-alpha
      blocker are warranted in cholestatic autoimmune hepatitis patients, and in
      particular in those individuals in whom the disease is associated with
      inflammatory arthropathies.

PMID- 27876038
TI  - Parental perception of built environment characteristics and built environment
      use among Latino families: a cross-sectional study.
AB  - BACKGROUND: Perception of undesirable features may inhibit built environment use
      for physical activity among underserved families with children at risk for
      obesity. METHODS: To examine the association of perceived availability,
      condition, and safety of the built environment with its self-reported use for
      physical activity, we conducted a cross-sectional analysis on baseline data from
      a randomized controlled trial. Adjusted Poisson regression was used to test the
      association between the primary independent variables (perceived availability,
      physical condition, and safety) with the primary outcome of self-reported use of
      built environment structures. RESULTS: Among 610 parents (90% Latino) of
      preschool-age children, 158 (26%) reported that there were no available built
      environment structures for physical activity in the neighborhood. The use of
      built environment structures was associated with the perceived number of
      available structures (B = 0.34, 95% CI 0.31, 0.37, p < 0.001) and their perceived
      condition (B = 0.19, 95% CI 0.12, 0.27, p = 0.001), but not with perceived safety
      (B = 0.00, 95% CI -0.01, 0.01, p = 0.7). CONCLUSIONS: In this sample of
      underserved families, perceived availability and condition of built environment
      structures were associated with use rather than perceived safety. To encourage
      physical activity among underserved families, communities need to invest in the
      condition and availability of built environment structures. TRIAL REGISTRATION:
      Registered at ClinicalTrials.gov ( NCT01316653 ) on March 11, 2011.

PMID- 27876040
TI  - Botulinum toxin treatment for essential palatal tremors presenting with nasal
      clicks instead of pulsatile tinnitus: a case report.
AB  - BACKGROUND: In this study, we report a rare case of an adult patient with
      essential palatal tremors (EPT) presenting as nasal clicks, instead of otic
      clicks or objective pulsatile tinnitus in common EPT. CASE PRESENTATION: Nasal
      endoscopic examination and EMG recordings of the soft palate muscles were
      performed to confirm the source of the clicks. Initial treatment with lidocaine
      provided symptomatic relief for four hours. The patient was then treated with
      four simultaneous injections of 12.5 U of botulinum toxin in four different sites
      of the soft palate. Palatal tremors and clicks completely disappeared within
      three months of treatment. CONCLUSIONS: To our knowledge, this is the first case
      of EPT that presented with nasal clicks. We recommend that otolaryngologists
      should expect this rare occurrence in the clinical setting, and handle patients
      presenting with such symptoms with care and compassion in order not to worsen
      their psychological status.

PMID- 27876041
TI  - Time series analysis of malaria in Afghanistan: using ARIMA models to predict
      future trends in incidence.
AB  - BACKGROUND: Malaria remains endemic in Afghanistan. National control and
      prevention strategies would be greatly enhanced through a better ability to
      forecast future trends in disease incidence. It is, therefore, of interest to
      develop a predictive tool for malaria patterns based on the current passive and
      affordable surveillance system in this resource-limited region. METHODS: This
      study employs data from Ministry of Public Health monthly reports from January
      2005 to September 2015. Malaria incidence in Afghanistan was forecasted using
      autoregressive integrated moving average (ARIMA) models in order to build a
      predictive tool for malaria surveillance. Environmental and climate data were
      incorporated to assess whether they improve predictive power of models. RESULTS:
      Two models were identified, each appropriate for different time horizons. For
      near-term forecasts, malaria incidence can be predicted based on the number of
      cases in the four previous months and 12 months prior (Model 1); for longer-term
      prediction, malaria incidence can be predicted using the rates 1 and 12 months
      prior (Model 2). Next, climate and environmental variables were incorporated to
      assess whether the predictive power of proposed models could be improved.
      Enhanced vegetation index was found to have increased the predictive accuracy of
      longer-term forecasts. CONCLUSION: Results indicate ARIMA models can be applied
      to forecast malaria patterns in Afghanistan, complementing current surveillance
      systems. The models provide a means to better understand malaria dynamics in a
      resource-limited context with minimal data input, yielding forecasts that can be
      used for public health planning at the national level.

PMID- 27876039
TI  - Evidence of a multiple insecticide resistance in the malaria vector Anopheles
      funestus in South West Nigeria.
AB  - BACKGROUND: Knowing the extent and spread of insecticide resistance in malaria
      vectors is vital to successfully manage insecticide resistance in Africa. This
      information in the main malaria vector, Anopheles funestus sensu stricto, is
      completely lacking in the most populous country in Africa, Nigeria. This study
      reports the insecticide susceptibility status and the molecular basis of
      resistance of An. funestus as well as its involvement in malaria transmission in
      Akaka-Remo, a farm settlement village in southwest Nigeria. RESULTS: Plasmodium
      infection analysis using TaqMan protocol coupled with a nested PCR revealed an
      infection rate of 8% in An. funestus s.s. from Akaka-Remo. WHO susceptibility
      tests showed this species has developed multiple resistance to insecticides in
      the study area. Anopheles funestus s.s. population in Akaka-Remo is highly
      resistant to organochlorines: dieldrin (8%) and DDT (10%). Resistance was also
      observed against pyrethroids: permethrin (68%) and deltamethrin (87%), and the
      carbamate bendiocarb (84%). Mortality rate with DDT slightly increased (from 10
      to 30%, n = 45) after PBO pre-exposure indicating that cytochrome P450s play
      little role in DDT resistance while high mortalities were recorded after PBO pre
      exposure with permethrin (from 68 to 100%, n = 70) and dieldrin (from 8 to 100%,
      n = 48) suggesting the implication of P450s in the observed permethrin and
      dieldrin resistance. High frequencies of resistant allele, 119F in F0 (77%) and
      F1 (80% in resistant and 72% in susceptible) populations with an odd ratio of
      1.56 (P = 0.1859) show that L119F-GSTe2 mutation is almost fixed in the
      population. Genotyping of the A296S-RDL mutation in both F0 and F1 samples shows
      an association with dieldrin resistance with an odd ratio of 81 (P < 0.0001)
      (allelic frequency (R) = 76% for F0; for F1, 90 and 10% were observed in
      resistant and susceptible populations, respectively) as this mutation is not yet
      fixed in the population. CONCLUSION: The study reports multiple insecticide
      resistance in An. funestus from Akaka Remo. It is, therefore, necessary to pay
      more attention to this major malaria vector for effective malaria control in
      Nigeria.

PMID- 27876042
TI  - The effect of screw thread length on initial stability of Schatzker type 1 tibial
      plateau fracture fixation: a biomechanical study.
AB  - BACKGROUND: This study compares the cyclic loading properties and failure loads
      of two screw combinations on a synthetic Schatzker type 1 tibia fracture model.
      Our hypothesis was that after adequate compression with first a partially
      threaded screw, addition of a fully threaded screw would provide more stability
      than an addition of a second partially threaded screw. METHODS: The Schatzker
      type 1 tibial plateau fracture model was created. Fixation was obtained in group
      A (n = 10) with two partially threaded screws and in group B (n = 10) with one
      fully threaded screw and one partially threaded screw. Load-displacement
      evaluation was made at each 1000-cycle interval up to 10,000 cycles. Failure load
      was identified as the load creating a 2-mm displacement. Two-factor (groups and
      periods) repeated measurement analysis of variance and independent sample t tests
      were used. RESULTS: According to the two-factor repeated analysis, there was no
      significant difference for periods (p = 0.29) and time-period interaction (p =
      0.59) (Wilk's Lambda F value, 1.507 and 0.871, respectively). In the test of
      between-subject effects, there was no significant difference between groups in
      terms of cyclic loadings (p = 0.06, F = 4.065). However, in the t test for each
      1000-cycle interval, the value of mean displacement in group B was significantly
      lower than that in group A in the initial, 1000-, 2000-, and 3000-cycle intervals
      (p = 0.023, 0.031, 0.025, 0.043, respectively). The mean displacement and
      standard deviations increased with the number of cycles. The mean range of
      displacement initially was 0.66 mm for group A and 0.36 mm for group B. The mean
      range of displacement after 10,000 cycles was 0.79 mm for group A and 0.44 mm for
      group B. The mean failure load value was 682 +/- 234 N for group A and 835 +/-
      245 N for group B. In independent sample t tests, there were no significant
      differences between the two groups in terms of failure load (p > 0.05).
      CONCLUSIONS: Obtaining fixation with one partially and one fully threaded screw
      can minimize displacement at the fracture site at early cyclic loadings.

PMID- 27876043
TI  - Medical education in a foreign language and history-taking in the native language
      in Lebanon - a nationwide survey.
AB  - BACKGROUND: With the adoption of the English language in medical education, a gap
      in clinical communication may develop in countries where the native language is
      different from the language of medical education. This study investigates the
      association between medical education in a foreign language and students'
      confidence in their history-taking skills in their native language. METHODS: This
      cross-sectional study consisted of a 17-question survey among medical students in
      clinical clerkships of Lebanese medical schools. The relationship between the
      language of medical education and confidence in conducting a medical history in
      Arabic (the native language) was evaluated (n = 457). RESULTS: The majority
      (88.5%) of students whose native language was Arabic were confident they could
      conduct a medical history in Arabic. Among participants enrolled in the first
      clinical year, high confidence in Arabic history-taking was independently
      associated with Arabic being the native language and with conducting medical
      history in Arabic either in the pre-clinical years or during extracurricular
      activities. Among students in their second clinical year, however, these factors
      were not associated with confidence levels. CONCLUSIONS: Despite having their
      medical education in a foreign language, the majority of students in Lebanese
      medical schools are confident in conducting a medical history in their native
      language.

PMID- 27876044
TI  - Generation of monoclonal antibodies against native viral proteins using antigen
      expressing mammalian cells for mouse immunization.
AB  - BACKGROUND: Due to their rising incidence and progressive geographical spread,
      infections with mosquito-borne viruses, such as dengue (DENV), chikungunya and
      zika virus, have developed into major public health challenges. Since all of
      these viruses may cause similar symptoms and can occur in concurrent epidemics,
      tools for their differential diagnosis and epidemiological monitoring are of
      urgent need. RESULTS: Here we report the application of a novel strategy to
      rapidly generate monoclonal antibodies (mAbs) against native viral antigens,
      exemplified for the DENV nonstructural glycoprotein 1 (NS1). The described system
      is based on the immunization of mice with transfected mammalian cells expressing
      the target antigens in multiple displays on their cell surface and thereby
      presenting them efficiently to the host immune system in their native
      conformation. By applying this cell-based approach to the DENV NS1 protein of
      serotypes 1 (D1NS1) and 4 (D4NS1), we were able to rapidly generate panels of
      DENV NS1 serotype cross-reactive, as well as D1NS1- and D4NS1 serotype-specific
      mAbs. Our data show that the generated mAbs were capable of recognizing the
      endogenous NS1 protein in DENV-containing biological samples. CONCLUSION: The use
      of this novel immunization strategy, allows for a fast and efficient generation
      of hybridoma cell lines, producing mAbs against native viral antigens. Envisaged
      applications of the mAbs include the development of test platforms enabling a
      differentiation of the DENV serotypes and high resolution immunotyping for
      epidemiological studies.

PMID- 27876045
TI  - Seroprevalence of avian hepatitis E virus and avian leucosis virus subgroup J in
      chicken flocks with hepatitis syndrome, China.
AB  - BACKGROUND: From 2014 to 2015 in China, many broiler breeder and layer hen flocks
      exhibited a decrease in egg production and some chickens developed hepatitis
      syndrome including hepatomegaly, hepatic necrosis and hemorrhage. Avian hepatitis
      E virus (HEV) and avian leucosis virus subgroup J (ALV-J) both cause decreasing
      in egg production, hepatomegaly and hepatic hemorrhage in broiler breeder and
      layer hens. In the study, the seroprevalence of avian HEV and ALV-J in these
      flocks emerging the disease from Shandong and Shaanxi provinces were
      investigated. RESULTS: A total of 1995 serum samples were collected from 14
      flocks with hepatitis syndrome in Shandong and Shaanxi provinces, China.
      Antibodies against avian HEV and ALV-J in these serum samples were detected using
      iELISAs. The seroprevalence of anti-avian HEV antibodies (35.09%) was
      significantly higher than that of anti-ALV-J antibodies (2.16%) (p = 0.00).
      Moreover, the 43 serum samples positive for anti-ALV-J antibodies were all also
      positive for anti-avian HEV antibodies. In a comparison of both provinces,
      Shandong chickens exhibited a significantly higher seroprevalence of anti-avian
      HEV antibodies (42.16%) than Shaanxi chickens (26%) (p = 0.00). In addition, the
      detection of avian HEV RNA and ALV-J cDNA in the liver samples from the flocks of
      two provinces also showed the same results of the seroprevalence. CONCLUSIONS: In
      the present study, the results showed that avian HEV infection is widely
      prevalent and ALV-J infection is endemic in the flocks with hepatitis syndrome
      from Shandong and Shaanxi provinces of China. These results suggested that avian
      HEV infection may be the major cause of increased egg drop and hepatitis syndrome
      observed during the last 2 years in China. These results should be useful to
      guide development of prevention and control measures to control the diseases
      within chicken flocks in China.

PMID- 27876047
TI  - Effects of longitudinal changes in Charlson comorbidity on prognostic survival
      model performance among newly diagnosed patients with hypertension.
AB  - BACKGROUND: To assess the use of updated comorbidity information over time on
      ability to predict mortality among adults with newly diagnosed hypertension.
      METHODS: We studied adults 18 years and older with an incident diagnosis of
      hypertension from Alberta, Canada. We compared the prognostic performance of Cox
      regression models using Charlson comorbidities as time-invariant covariates at
      baseline (TIC) versus models including Charlson comorbidities as time-varying
      covariates (TVC) using Akaike Information Criterion (AIC) for testing goodness of
      fit. RESULTS: The strength of the association between important prognostic
      clinical variables and mortality varied by modeling technique; for example,
      myocardial infarction was less strongly associated with mortality in the TIC
      model (Hazard Ratio 1.07; 95% Confidence Interval (CI): 1.05 to 1.1) than in the
      TVC model (HR 1.20; 95% CI: 1.18 to 1.22). All TVC models slightly outperformed
      TIC models, regardless of the method used to adjust for comorbid conditions
      (individual Charlson Comorbidities, count of comorbidities or indices). The TVC
      model including all 17 Charlson comorbidities as individual independent variables
      showed the best fit and performance. CONCLUSION: Accounting for changes in
      patient comorbidity status over time more accurately captures a patient's health
      risk and slightly improves predictive model fit and performance than traditional
      methods using TIC assessment.

PMID- 27876048
TI  - An integrated approach to care attracts people living with HIV who use illicit
      drugs in an urban centre with a concentrated HIV epidemic.
AB  - BACKGROUND: People living with HIV (PLHIV) who are also marginalized by social
      and structural inequities often face barriers to accessing and adhering to HIV
      treatment and care. The Dr. Peter Centre (DPC) is a non-profit integrated care
      facility with a supervised injection room that serves PLHIV experiencing multiple
      barriers to social and health services in Vancouver, Canada. This study examines
      whether the DPC is successful in drawing in PLHIV with complex health issues,
      including addiction. METHODS: Using data collected by the Longitudinal
      Investigations into Supportive and Ancillary health services (LISA) study from
      July 2007 to January 2010, linked with clinical variables available through the
      British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program, we
      identified DPC and non-DPC clients with a history of injection drug use.
      Bivariable and multivariable logistic regression analyses compared socio
      demographic and clinical characteristics of DPC clients (n = 76) and non-DPC
      clients (n = 482) with a history of injection drug use. RESULTS: Of the 917 LISA
      participants included within this analysis, 100 (10.9%) reported being a DPC
      client, of which 76 reported a history of injection drug use. Adjusted results
      found that compared to non-DPC clients with a history of injection drug use, DPC
      clients were more likely to be male (AOR: 4.18, 95% CI = 2.09-8.37); use
      supportive services daily vs. less than daily (AOR: 3.16, 95% CI = 1.79-5.61); to
      have been diagnosed with a mental health disorder (AOR: 2.11; 95% CI: 1.12-3.99);
      to have a history of interpersonal violence (AOR: 2.76; 95% CI: 1.23-6.19); and
      to have ever experienced ART interruption longer than 1 year (AOR: 2.39; 95% CI:
      1.38-4.15). CONCLUSIONS: Our analyses suggest that the DPC operating care model
      engages PLHIV with complex care needs, highlighting that integrated care
      facilities are needed to support the multiple intersecting vulnerabilities faced
      by PLHIV with a history of injection drug use living within urban centres in
      North America and beyond.

PMID- 27876046
TI  - Increasing insecticide resistance in Anopheles funestus and Anopheles arabiensis
      in Malawi, 2011-2015.
AB  - BACKGROUND: Susceptibility of principal Anopheles malaria vectors to common
      insecticides was monitored over a 5-year period across Malawi to inform and guide
      the national malaria control programme. METHODS: Adult blood-fed Anopheles spp.
      and larvae were collected from multiple sites in sixteen districts across the
      country between 2011 and 2015. First generation (F1) progeny aged 2-5 days old
      were tested for susceptibility, using standard WHO procedures, against
      pyrethroids (permethrin and deltamethrin), carbamates (bendiocarb and propoxur),
      organophosphates (malathion and pirimiphos-methyl) and an organochlorine (DDT).
      RESULTS: Mortality of Anopheles funestus to deltamethrin, permethrin, bendiocarb
      and propoxur declined significantly over the 5-year (2011-2015) monitoring
      period. There was wide variation in susceptibility to DDT but it was not
      associated with time. In contrast, An. funestus exhibited 100% mortality to the
      organophosphates (malathion and pirimiphos-methyl) at all sites tested. There was
      reduced mortality of Anopheles arabiensis to deltamethrin over time though this
      was not statistically significant. However, mortality of An. arabiensis exposed
      to permethrin declined significantly over time. Anopheles arabiensis exposed to
      DDT were more likely to be killed if there was high ITN coverage in the mosquito
      collection area the previous year. There were no other associations between
      mosquito mortality in a bioassay and ITN coverage or IRS implementation.
      Mortality of An. funestus from four sites exposed to deltamethrin alone ranged
      from 2 to 31% and from 41 to 94% when pre-exposed to the synergist piperonyl
      butoxide followed by deltamethrin. For permethrin alone, mortality ranged from 2
      to 13% while mortality ranged from 63 to 100% when pre-exposed to PBO.
      CONCLUSION: Pyrethroid resistance was detected in An. funestus and An. arabiensis
      populations across Malawi and has worsened over the last 5 years. New
      insecticides and control strategies are urgently needed to reduce the burden of
      malaria in Malawi.

PMID- 27876049
TI  - Geographical predisposition influences on the distribution and tissue
      characterisation of eccentric coronary plaques in non-branching coronary
      arteries: cross-sectional study of coronary plaques analysed by intravascular
      ultrasound.
AB  - BACKGROUND: We investigated the influence of geographical predisposition on the
      spatial distribution and composition of coronary plaques. METHODS: Thirty
      coronary arteries were evaluated. A total of 1441 cross-sections were collected
      from intravascular ultrasound (IVUS) and radio-frequency signal-based virtual
      histology (VH-IVUS) imaging. To exclude complex geographical effects of side
      branches and to localise the plaque distribution, we analysed only eccentric
      plaques in non-branching regions. The spatial distribution of eccentric plaques
      in the coronary artery was classified into myocardial, lateral, and epicardial
      regions. The composition of eccentric plaques was analysed using VH-IVUS.
      RESULTS: The plaque was concentric in 723 sections (50.2%) and eccentric in 718
      (49.9%). Eccentric plaques were more frequently distributed towards the
      myocardial side than towards the epicardial side (46.7 +/- 7.5% vs. 12.5 +/-
      4.2%, p = 0.003). No significant difference was observed between the myocardial
      and lateral sides (46.7 +/- 7.5% vs. 20.8 +/- 5.0%) or between the lateral and
      epicardial sides. Eccentric thin-capped fibroatheromas were more frequently
      distributed towards the myocardial side than towards the lateral side (p = 0.024)
      or epicardial side (p = 0.005). CONCLUSION: Geographical predisposition is
      associated with distribution, tissue characterisation, and vulnerability of
      plaques in non-branching coronary arteries.

PMID- 27876050
TI  - Studies on mosquito biting risk among migratory rice farmers in rural south
      eastern Tanzania and development of a portable mosquito-proof hut.
AB  - BACKGROUND: Subsistence rice farmers in south-eastern Tanzania are often
      migratory, spending weeks or months tending to crops in distant fields along the
      river valleys and living in improvised structures known as Shamba huts, not fully
      protected from mosquitoes. These farmers also experience poor access to organized
      preventive and curative services due to long distances. Mosquito biting exposure
      in these rice fields, relative to main village residences was assessed, then a
      portable mosquito-proof hut was developed and tested for protecting these
      migratory farmers. METHODS: Pair-wise mosquito surveys were conducted in four
      villages in Ulanga district, south-eastern Tanzania in 20 randomly-selected
      Shamba huts located in the distant rice fields and in 20 matched houses within
      the main villages, to assess biting densities and Plasmodium infection rates. A
      portable mosquito-proof hut was designed and tested in semi-field and field
      settings against Shamba hut replicas, and actual Shamba huts. Also, semi
      structured interviews were conducted, timed-participant observations, and focus
      group discussions to assess experiences and behaviours of the farmers regarding
      mosquito-bites and the mosquito-proof huts. RESULTS: There were equal numbers of
      mosquitoes in Shamba huts and main houses [RR (95% CI) 27 (25.1-31.2), and RR
      (95% CI) 30 (27.5-33.4)], respectively (P > 0.05). Huts having >1 occupant had
      more mosquitoes than those with just one occupant, regardless of site [RR (95%
      CI) 1.57 (1.30-1.9), P < 0.05]. Open eaves [RR (95% CI) 1.15 (1.08-1.23), P <
      0.05] and absence of window shutters [RR (95% CI) 2.10 (1.91-2.31), P < 0.05]
      increased catches of malaria vectors. All Anopheles mosquitoes caught were
      negative for Plasmodium. Common night-time outdoor activities in the fields
      included cooking, eating, fetching water or firewood, washing dishes, bathing,
      and storytelling, mostly between 6 and 11 p.m., when mosquitoes were also biting
      most. The prototype hut provided 100% protection in semi-field and field
      settings, while blood-fed mosquitoes were recaptured in Shamba huts, even when
      occupants used permethrin-impregnated bed nets. CONCLUSION: Though equal numbers
      of mosquitoes were caught between main houses and normal Shamba huts, the higher
      proportions of blood-fed mosquitoes, reduced access to organized healthcare and
      reduced effectiveness of LLINs, may increase vulnerability of the itinerant
      farmers. The portable mosquito-proof hut offered sufficient protection against
      disease-transmitting mosquitoes. Such huts could be improved to expand protection
      for migratory farmers and possibly other disenfranchised communities.

PMID- 27876052
TI  - Implementing the United Kingdom's ten-year teenage pregnancy strategy for England
      (1999-2010): How was this done and what did it achieve?
AB  - BACKGROUND: In 1999, the UK Labour Government launched a 10-year Teenage
      Pregnancy Strategy for England to address the country's historically high rates
      and reduce social exclusion. The goal was to halve the under-18 conception rate.
      This study explores how the strategy was designed and implemented, and the
      features that contributed to its success. METHODS: This study was informed by
      examination of the detailed documentation of the strategy, published throughout
      its 10-year implementation. RESULTS: The strategy involved a comprehensive
      programme of action across four themes: joined up action at national and local
      level; better prevention through improved sex and relationships education and
      access to effective contraception; a communications campaign to reach young
      people and parents; and coordinated support for young parents (The support
      programme for young parents was an important contribution to the strategy. In the
      short term by helping young parents prevent further unplanned pregnancies and, in
      the long term, by breaking intergenerational cycles of disadvantage and lowering
      the risk of teenage pregnancy.). It was implemented through national, regional
      and local structures with dedicated funding for the 10-year duration. The under
      18 conception rate reduced steadily over the strategy's lifespan. The 2014 under
      18 conception rate was 51% lower than the 1998 baseline and there have been
      significant reductions in areas of high deprivation. One leading social
      commentator described the strategy as 'The success story of our time' (Toynbee,
      The drop in teenage pregnancies is the success story of our time, 2013).
      CONCLUSIONS: As rates of teenage pregnancy are influenced by a web of inter
      connected factors, the strategy was necessarily multi-faceted in its approach. As
      such, it is not possible to identify causative pathways or estimate the relative
      contributions of each constituent part. However, we conclude that six key
      features contributed to the success: creating an opportunity for action;
      developing an evidence based strategy; effective implementation; regularly
      reviewing progress; embedding the strategy in wider government programmes; and
      providing leadership throughout the programme. The learning remains relevant for
      the UK as England's teenage birth rate remains higher than in other Western
      European countries. It also provides important lessons for governments and policy
      makers in other countries seeking to reduce teenage pregnancy rates.

PMID- 27876051
TI  - Dietary marine-derived long-chain monounsaturated fatty acids and cardiovascular
      disease risk: a mini review.
AB  - Regular fish/fish oil consumption is widely recommended for protection against
      cardiovascular diseases (CVD). Fish and other marine life are rich sources of the
      cardioprotective long-chain n-3 polyunsaturated fatty acids (n-3 PUFA)
      eicosapentaenoic acid (C20:5 n-3; EPA) and docosahexaenoic acid (C22:6 n-3; DHA).
      The lipid content and fatty acid profile of fish, however, vary greatly among
      different fish species. In addition to n-3 PUFA, certain fish, such as saury,
      pollock, and herring, also contain high levels of long-chain monounsaturated
      fatty acids (LCMUFA), with aliphatic tails longer than 18 C atoms (i.e., C20:1
      and C22:1 isomers). Compared with well-studied n-3 PUFA, limited information,
      however, is available on the health benefits of marine-derived LCMUFA,
      particularly in regard to CVD. Our objective in this review is to summarize the
      current knowledge and provide perspective on the potential therapeutic value of
      dietary LCMUFA-rich marine oil for improving CVD risk factors. We will also
      review the possible mechanisms of LCMUFA action on target tissues. Finally, we
      describe the epidemiologic data and small-scaled clinical studies that have been
      done on marine oils enriched in LCMUFA. Although there are still many unanswered
      questions about LCMUFA, this appears to be promising new area of research that
      may lead to new insights into the health benefits of a different component of
      fish oils besides n-3 PUFA.

PMID- 27876053
TI  - Three years follow-up after cryoablation of a right atrial myxoma arising from
      the Koch's triangle.
AB  - We reported 3 years ago the use of cryoablation in the treatment of a right
      atrium myxoma arising from the Koch's triangle. The atrioventricular conduction
      was successfully preserved. Today, after 3 years follow-up, the patient remains
      with a conducted sinus rhythm and is free of recurrence. Even if extensive
      resection of the stack of the myxoma remains the first choice attitude,
      cryoablation could be considered as a serious second choice alternative.

PMID- 27876054
TI  - Engineering an inducible gene expression system for Bacillus subtilis from a
      strong constitutive promoter and a theophylline-activated synthetic riboswitch.
AB  - BACKGROUND: Synthetic riboswitches have been increasingly used to control and
      tune gene expression in diverse organisms. Although a set of theophylline
      responsive riboswitches have been developed for bacteria, fully functional
      expression elements mediated by synthetic riboswitches in Bacillus subtilis are
      rarely used because of the host-dependent compatibility between the promoters and
      riboswitches. RESULTS: A novel genetic element composed of the promoter P43 and a
      theophylline-riboswitch was developed and characterized in B. subtilis. When
      combined with a P43 promoter (P43'-riboE1), the theophylline-riboswitch
      successfully switched the constitutive expression pattern of P43 to an induced
      pattern. The expression mediated by the novel element could be activated at the
      translational level by theophylline with a relatively high induction ratio. The
      induction ratios for P43'-riboE1 by 4-mM theophylline were elevated during the
      induction period. The level of induced expression was dependent on the
      theophylline dose. Correspondingly, the induction ratios gradually increased in
      parallel with the elevated dose of theophylline. Importantly, the induced
      expression level was higher than three other strong constitutive promoters
      including PsrfA, PaprE, and the native P43. It was found that the distance
      between the SD sequence within the expression element and the start codon
      significantly influenced both the level of induced expression and the induction
      ratio. A 9-bp spacer was suitable for producing desirable expression level and
      induction ratio. Longer spacer reduced the activation efficiency. Importantly,
      the system successfully overexpressed beta-glucuronidase at equal levels, and
      induction ratio was similar to that of GFP. CONCLUSION: The constructed
      theophylline-inducible gene expression system has broad compatibility and
      robustness, which has great potential in over-production of pharmaceutical and
      industrial proteins and utilization in building more complex gene circuits.

PMID- 27876055
TI  - Methanolic extract of Agerantum conyzoides exhibited toxicity and growth
      disruption activities against Anopheles gambiae sensu stricto and Anopheles
      arabiensis larvae.
AB  - BACKGROUND: Vector control remains the mainstay to effective malaria management.
      The negative implications following persistent application of synthetic
      insecticides geared towards regulation of mosquito populations have necessitated
      prospection for ecofriendly effective chemistries. Plant-derived compounds have
      the potential to control malaria-transmitting mosquito populations. Previously,
      Agerantum conyzoides extracts have demonstrated toxicity effects on disease
      transmitting mosquitoes. However, their efficacy in controlling Afrotropical
      malaria vectors remains unclear. Herein, the toxicity and growth disruption
      activities of crude methanolic leaf extract of A. conyzoides on Anopheles gambiae
      sensu stricto and An. arabiensis larvae were assessed. METHODS: Late third (L3)
      instars of An. gambiae s.s and An. arabiensis larvae were challenged with
      increasing doses of crude methanolic extract of A. conyzoides. The larval
      mortality rates were recorded every 24 h and the LC50 values determined at their
      associated 95% confidence levels. ANOVA followed by Post-hoc Student-Newman-Keuls
      (SNK) test was used to compare results between treatment and control groups.
      Phytochemical profiling of the extract was performed using standard chemical
      procedures. RESULTS: Treatment of larvae with the methanolic extract depicted
      dose-dependent effects with highest mortality percentages of >= 69% observed when
      exposed with 250 ppm and 500 ppm for 48 h while growth disruption effects were
      induced by sublethal doses of between 50-100 ppm for both species. Relative to
      experimental controls, the extract significantly reduced larval survival in both
      mosquito species (ANOVA, F(8,126) = 43.16776, P < 0.001). The LC50 values of the
      extract against An. gambiae s.s ranged between 84.71-232.70 ppm (95% CI 81.17
      239.20), while against An. arabiensis the values ranged between 133.46-406.35 ppm
      (95% CI 131.51-411.25). The development of the juvenile stages was arrested at
      pupal-larval intermediates and adult emergence. The presence of alkaloids,
      aglycone flavonoids, triterpenoids, tannins and coumarins can partly be
      associated with the observed effects. CONCLUSION: The extract displayed
      considerable larvicidal activity and inhibited emergence of adult mosquitoes
      relative to experimental controls, a phenomenon probably associated with induced
      developmental hormone imbalance. Optimization of the bioactive compounds could
      open pathways into vector control programmes for improved mosquito control and
      reduced malaria transmission rates.

PMID- 27876056
TI  - Post universal health coverage trend and geographical inequalities of mortality
      in Thailand.
AB  - BACKGROUND: Thailand has achieved remarkable improvement in health status since
      the achievement of universal health coverage in 2002. Health equity has improved
      significantly. However, challenges on health inequity still remain.This study
      aimed to determine the trends of geographical inequalities in disease specific
      mortality in Thailand after the country achieved universal health coverage.
      METHODS: National vital registration data from 2001 to 2014 were used to
      calculate age-adjusted mortality rate and standardized mortality ratio (SMR). To
      minimize large variations in mortality across administrative districts, the
      adjacent districts were systematically grouped into "super-districts" by taking
      into account the population size and proximity. Geographical mortality inequality
      among super-districts was measured by the coefficient of variation. Mixed effects
      modeling was used to test the difference in trends between super-districts.
      RESULTS: The overall SMR steadily declined from 1.2 in 2001 to 0.9 in 2014. The
      upper north and upper northeast regions had higher SMR whereas Greater Bangkok
      achieved the lowest SMR. Decreases in SMR were mostly seen in Greater Bangkok and
      the upper northern region. Coefficient of variation of SMR rapidly decreased from
      20.0 in 2001 to 12.5 in 2007 and remained close to this value until 2014. The
      mixed effects modelling revealed significant differences in trends of SMR across
      super-districts. Inequality in mortality declined among adults (>=15 years old)
      but increased in children (0-14 years old). A declining trend in inequality of
      mortality was seen in almost all regions except Greater Bangkok where the
      inequality in SMR remained high throughout the study period. CONCLUSIONS: A
      decline in the adult mortality inequality across almost all regions of Thailand
      followed universal health coverage. Inequalities in child mortality rates and
      among residents of Greater Bangkok need further exploration.

PMID- 27876057
TI  - Bridging the gap between clinicians and systems biologists: from network biology
      to translational biomedical research.
AB  - With the wealth of data accumulated from completely sequenced genomes and other
      high-throughput experiments, global studies of biological systems, by
      simultaneously investigating multiple biological entities (e.g. genes,
      transcripts, proteins), has become a routine. Network representation is
      frequently used to capture the presence of these molecules as well as their
      relationship. Network biology has been widely used in molecular biology and
      genetics, where several network properties have been shown to be functionally
      important. Here, we discuss how such methodology can be useful to translational
      biomedical research, where scientists traditionally focus on one or a small set
      of genes, diseases, and drug candidates at any one time. We first give an
      overview of network representation frequently used in biology: what nodes and
      edges represent, and review its application in preclinical research to date.
      Using cancer as an example, we review how network biology can facilitate system
      wide approaches to identify targeted small molecule inhibitors. These types of
      inhibitors have the potential to be more specific, resulting in high efficacy
      treatments with less side effects, compared to the conventional treatments such
      as chemotherapy. Global analysis may provide better insight into the overall
      picture of human diseases, as well as identify previously overlooked problems,
      leading to rapid advances in medicine. From the clinicians' point of view, it is
      necessary to bridge the gap between theoretical network biology and practical
      biomedical research, in order to improve the diagnosis, prevention, and treatment
      of the world's major diseases.

PMID- 27876059
TI  - A prospective observational cohort study in primary care practices to identify
      factors associated with treatment failure in Staphylococcus aureus skin and soft
      tissue infections.
AB  - BACKGROUND: The incidence of outpatient visits for skin and soft tissue
      infections (SSTIs) has substantially increased over the last decade. The
      emergence of community-associated methicillin-resistant Staphylococcus aureus (CA
      MRSA) has made the management of S. aureus SSTIs complex and challenging. The
      objective of this study was to identify risk factors contributing to treatment
      failures associated with community-associated S. aureus skin and soft tissue
      infections SSTIs. METHODS: This was a prospective, observational study among 14
      primary care clinics within the South Texas Ambulatory Research Network. The
      primary outcome was treatment failure within 90 days of the initial visit.
      Univariate associations between the explanatory variables and treatment failure
      were examined. A generalized linear mixed-effect model was developed to identify
      independent risk factors associated with treatment failure. RESULTS: Overall, 21%
      (22/106) patients with S. aureus SSTIs experienced treatment failure. The
      occurrence of treatment failure was similar among patients with methicillin
      resistant S. aureus and those with methicillin-susceptible S. aureus SSTIs (19
      vs. 24%; p = 0.70). Independent predictors of treatment failure among cases with
      S. aureus SSTIs was a duration of infection of >=7 days prior to initial visit
      [aOR, 6.02 (95% CI 1.74-19.61)] and a lesion diameter size >=5 cm [5.25 (1.58
      17.20)]. CONCLUSIONS: Predictors for treatment failure included a duration of
      infection for >=7 days prior to the initial visit and a wound diameter of >=5 cm.
      A heightened awareness of these risk factors could help direct targeted
      interventions in high-risk populations.

PMID- 27876058
TI  - A novel non-Hodgkin lymphoma murine model closer to the standard clinical
      scenario.
AB  - BACKGROUND: Non-Hodgkin lymphomas (NHL) are the most frequent hemato-oncological
      malignancies. Despite recent major advances in treatment, a substantial
      proportion of patients relapses highlighting the need for new therapeutic
      modalities. Promissory results obtained in pre-clinical studies are usually not
      translated when moving into clinical trials. Pre-clinical studies are mainly
      conducted in animals with high tumor burden; instead patients undergo
      chemotherapy as first line of treatment and most likely are under remission when
      immunotherapies are applied. Thus, an animal model that more closely resembles
      patients' conditions would be a valuable tool. METHODS: BALB/c mice were injected
      subcutaneously with A20 lymphoma cells and after tumor development different
      doses of chemotherapy were assessed to find optimal conditions for minimal
      residual disease (MRD) establishment. Tumor growth and survival, as well as drugs
      side effects, were all evaluated. Complete lymphoma remission was monitored in
      vivo using positron emission tomography (PET), and the results were correlated
      with histology. Immunological status was assessed by splenocytes proliferation
      assays in NHL-complete remission mice and by analyzing tumor cell infiltrates and
      chemokines/cytokines gene expression in the tumor microenvironment of animals
      with residual lymphoma. RESULTS: Two cycles of CHOP chemotherapy at days 25 and
      35 post-tumor implantation induced complete remission for around 20 days. PET
      showed to be a suitable follow-up technique for MRD condition with 85.7 and 75%
      of sensibility and specificity respectively. Proliferative responses upon mitogen
      stimulation were similar in animals that received chemotherapy and wild type
      mice. Tumors from animals with residual lymphoma showed higher numbers of CD4+
      and CD8+ and similar numbers of NK, neutrophils and Tregs infiltrating cells as
      compared with non-treated animals. Gene expression of several cytokines as well
      as an array of chemokines associated with migration of activated T cells to tumor
      sites was upregulated in the tumor microenvironment of animals that received
      chemotherapy treatment. CONCLUSIONS: We established a NHL-B pre-clinical model
      using standard chemotherapy to achieve MRD in immunocompetent animals. The MRD
      condition is maintained for approximately 20 days providing a therapeutic window
      of time where new immunotherapies can be tested in conditions closer to the
      clinics.

PMID- 27876060
TI  - 20-year follow-up study of Danish HHT patients-survival and causes of death.
AB  - BACKGROUND: Hereditary Haemorrhagic Telangiectasia (HHT) is a dominantly
      inheritable disorder, with a wide variety of clinical manifestations due to
      presence of multiple arteriovenous manifestations. The most common mutations are
      found in HHT1 (ENG) and HHT2 (ACVRL1) patients, causing alterations in the TGF
      beta pathway which is responsible for angiogenesis. Modulations of angiogenesis
      may influence cancer rates. The objective of the study was to evaluate 20-year
      survival according to HHT subtype, as well as to evaluate differences in causes
      of death comparing HHT patients and controls. We also wanted to investigate
      whether cancer morbidity among HHT patients differs from that among controls.
      RESULTS: We included all HHT patients in the County of Fyn, Denmark, prevalent as
      of January 1st 1995 in total 73 HHT patients. In addition three age- and sex-
      matched controls per HHT patient were evaluated, in total 218 controls (one was
      lost due to registration failure). The controls were defined at start of follow
      up in 1995. Information on lifestyle factors was not available. A total of 32
      (44%) HHT patients and 97 (44%) controls passed away during follow-up. The
      survival curves were evenly distributed showing similar survival rates in the two
      groups. Cancer diagnoses had been registered in the follow-up period in 4 (5%)
      HHT patients and in 38 (17%) controls. CONCLUSION: The mortality was not
      increased among Danish HHT patients compared to controls. This study is based on
      a clinical unselected series of HHT patients with the whole spectrum of severity,
      independent of need for medical care. Our data also suggest that HHT patients to
      a lesser degree than the background population are affected by cancer.

PMID- 27876061
TI  - Associations of DNMT3B -149C>T and -2437T>A polymorphisms and lung cancer risk in
      Chinese population.
AB  - BACKGROUND: DNMT3B polymorphisms are associated with the susceptibility of lung
      cancer. DNMT3B -2437T>A is a novel polymorphism, and its influence on the risk of
      lung cancer in Chinese was investigated in this study. In addition, effect of
      DNMT3B -149C>T polymorphism on lung cancer was also explored. METHODS: Genotyping
      in subjects were performed by PCR-RFLP. Haplotype frequencies were estimated by
      estimating haplotype software. Adjusted odds ratios (ORs) with 95% confidence
      intervals (CIs) were calculated by unconditional logistic regression analysis.
      RESULTS: Neither of the two polymorphisms was correlated with lung cancer (
      149C>T: CT+TT vs CC: OR = 0.78, 95%CI, 0.57 to 1.05, P = 0.361; -2437T>A: AT+AA
      vs TT: OR = 0.99, 95%CI, 0.74 to 1.33, P = 0.168). In stratification analysis, T
      allele carrier genotype of -149C>T polymorphism resulted in a reduced lung cancer
      risk at stage II, compared with CC (OR = 0.46, 95%CI, 0.28 to 0.77, P = 0.023).
      In haplotype analysis, when -149C/-2437T was used as reference, the other
      combined genotypes of the two polymorphisms had no significant effect on lung
      cancer risk (P > 0.05). CONCLUSIONS: The two DNMT3B polymorphisms are not
      correlated with lung cancer risk among Chinese population nor the haplotype of
      them.

PMID- 27876062
TI  - Elevated risk of incarceration among street-involved youth who initiate drug
      dealing.
AB  - BACKGROUND: Street-involved youth are known to be an economically vulnerable
      population that commonly resorts to risky activities such as drug dealing to
      generate income. While incarceration is common among people who use illicit drugs
      and associated with increased economic vulnerability, interventions among this
      population remain inadequate. Although previous research has documented the role
      of incarceration in further entrenching youth in both the criminal justice system
      and street life, less is known whether recent incarceration predicts initiating
      drug dealing among vulnerable youth. This study examines the relationship between
      incarceration and drug dealing initiation among street-involved youth. METHODS:
      Between September 2005 and November 2014, data were collected through the At-Risk
      Youth Study, a cohort of street-involved youth who use illicit drugs, in
      Vancouver, Canada. An extended Cox model with time-dependent variables was used
      to examine the relationship between recent incarceration and initiation into drug
      dealing, controlling for relevant confounders. RESULTS: Among 1172 youth
      enrolled, only 194 (16.6%) were drug dealing naive at baseline and completed at
      least one additional study visit to facilitate the assessment of drug dealing
      initiation. Among this sample, 56 (29%) subsequently initiated drug dealing. In
      final multivariable Cox regression analysis, recent incarceration was
      significantly associated with initiating drug dealing (adjusted hazard ratio =
      2.31; 95% confidence interval (CI) 1.21-4.42), after adjusting for potential
      confounders. Measures of recent incarceration lagged to the prior study follow-up
      were not found to predict initiation of drug dealing (hazard ratio = 1.50; 95% CI
      0.66-3.42). CONCLUSIONS: These findings suggest that among this study sample,
      incarceration does not appear to significantly propel youth to initiate drug
      dealing. However, the initiation of drug dealing among youth coincides with an
      increased risk of incarceration and their consequent vulnerability to the
      significant harms associated therein. Given that existing services tailored to
      street-involved youth are inadequate, evidence-based interventions should be
      invested and scaled up as a public health priority.

PMID- 27876063
TI  - Early and delayed assessments of quantitative gait measures to improve the tap
      test as a predictor of shunt effectiveness in idiopathic normal pressure
      hydrocephalus.
AB  - BACKGROUND: To improve the diagnostic performance of the cerebrospinal fluid
      (CSF) tap test (TT), early and delayed assessments of gait were performed after
      the removal of 30 ml of CSF in patients with probable idiopathic normal pressure
      hydrocephalus. Assessments of gait included the 3-m timed up and go test (TUG),
      and the 10-m walk in time (10Ti) and in step (10St) tests. METHODS: Quantitative
      data for the TUG, the 10Ti, and the 10St were obtained before CSF removal and on
      days 1 and 4 after removal of 30 ml CSF. CSF shunt surgery was performed in 61
      patients within one month after the TT. The gait outcome was assessed 3 months
      after surgery. The area under the curve (AUC), sensitivity, specificity, and
      cutoff values were computed for the TUG, the 10Ti, and the 10St on day 1 and day
      4 using receiver operating characteristic (ROC) curve analysis. RESULTS: The
      positive response rate in three measures on day 4 was equal to or higher than the
      values on day 1. Times were reduced significantly in the TUG and the 10mTi tests
      between baseline and both days 1 and 4 after TT. No significant differences were
      noted in the number of steps for the 10St test. The percent change in TUG on day
      1 had the highest AUC value among all other variables (0.808). Although this was
      not statistically different from other variables in the TUG and the 10Ti, it had
      a good balance of high sensitivity (78.3%) and high specificity (80.0%), with a
      cutoff value of 11.3%. The change in the measured value in the day 1 TUG had the
      second highest AUC value at 0.770. The variables on day 4 tended to have high
      specificities of around 90%, although their sensitivities were low. CONCLUSIONS:
      The percent change of TUG on day 1 showed the highest diagnostic accuracy.
      Delayed assessments on day 4 were not superior to those on day 1. Thus, the TUG
      on day 1 is useful as a simple quantitative measure for predicting shunt
      effectiveness.

PMID- 27876064
TI  - Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling
      in high-fat-diet-induced obese mice.
AB  - BACKGROUND: Melatonin can regulate lipid metabolism, increase insulin
      sensitivity, regulate glucose metabolism and reduce body weight. This study is
      aimed to determine the effects and mechanism of action of melatonin on non
      alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD) induced obese mice.
      METHODS: NAFLD was induced by HFD in C57BL/6 mice. A total of 24 mice were
      randomly assigned to 4 groups. Groups A and B were fed with HFD for 36 weeks
      while groups C and D were fed with a regular diet (RD). During the last 12 weeks,
      Groups A and C were treated with 10 mg/kg melatonin while Groups B and D were
      treated with water in the same volume by intragastric administration. Body and
      liver weight, blood glucose, serum transaminases and lipid levels, and markers of
      hepatic inflammation were measured. Histological analyses were also performed on
      liver tissue. RESULTS: After 12 weeks of treatment with melatonin, body weights
      (Group A: before 53.11 +/- 0.72 vs after 12w treatment 39.48 +/- 0.74) and liver
      weights (A 1.93 +/- 0.09 g vs B 2.92 +/- 0.19 g vs C 1.48 +/- 0.09 g vs D 1.49 +/
      0.10 g), fasting plasma glucose, alanine transaminase (A 24.33 +/- 11.90 IU/L vs
      B 60.80 +/- 10.18 IU/L vs C 13.01 +/- 3.49 IU/L vs D 16.62 +/- 2.00 IU/L), and
      low-density cholesterol (A 0.24 +/- 0.06 mmol/L vs B 1.57 +/- 0.10 mmol/L vs C
      0.28 +/- 0.06 mmol/L vs D 0.29 +/- 0.03 mmol/L) were significantly decreased in
      HFD mice. HFD fed mice treated with melatonin showed significantly less liver
      steatosis. Treatment of HFD fed mice with melatonin led to a significant decrease
      in the expression of TNF-alpha, IL-1beta, and IL-6 measured using quantitative
      real-time polymerase chain reaction (qRT-PCR). HFD fed mice demonstrated
      increased phosphorylation of P38 and JNK1/2, which was reduced by melatonin
      treatment. CONCLUSIONS: The study concluded that melatonin could improve NAFLD by
      decreasing body weight and reduce inflammation in HFD induced obese mice by
      modulating the MAPK-JNK/P38 signaling pathway.

PMID- 27876065
TI  - Expression of adiponectin receptors in human and rat intervertebral disc cells
      and changes in receptor expression during disc degeneration using a rat tail
      temporary static compression model.
AB  - BACKGROUND: Adipose tissue is a large endocrine organ known to secret
      adiponectin, which has anti-diabetic, anti-atherogenic, and anti-inflammatory
      properties. Adiponectin is widely involved in systemic disease, diabetes
      mellitus, and cardiac infraction. This study aimed to investigate the involvement
      of adiponectin in intervertebral disc (IVD) degeneration. METHODS: Adipose and
      IVD tissues were obtained from human patients undergoing surgery (n = 4) and from
      skeletally mature Sprague-Dawley rats (n = 21). Tissues were stained
      immunohistochemically for adiponectin and adiponectin receptors AdipoR1 and
      AdipoR2. Changes in adiponectin receptor expression with IVD degeneration
      severity were then investigated using a rat tail temporary compression model. Rat
      IVD tissues were stained immunohistochemically with AdipoR1 or AdipoR2, and
      immunopositive cell percentages were calculated. Rat nucleus pulposus (NP) and
      annulus fibrosus (AF) tissues were isolated separately and treated with
      recombinant adiponectin (Ad 0.1 or 1.0 MUg/ml) and/or interleukin-1 beta (IL
      1beta) (0.2 MUg/ml) for 24 h. The four groups were as follows: control group (no
      treatment), IL-1beta group (IL-1beta-only treatment), IL-1beta+Ad (0.1) group (IL
      1beta and adiponectin [0.1 MUg/ml] treatment), and IL-1beta+Ad (1.0) group (IL
      1beta and adiponectin [1.0 MUg/ml]). Real-time reverse transcription-polymerase
      chain reaction was performed to evaluate messenger-RNA (mRNA) expression of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). RESULTS: Adiponectin
      was widely expressed in human subcutaneous and epidural adipose tissue. In rat
      IVD tissue, adiponectin was not observed in NP and AF. However, both AdipoR1 and
      AdipoR2 were widely expressed in both human and rat IVD tissues, with no
      significant differences in expression levels between receptors. Furthermore,
      expression levels of AdipoR1 and AdipoR2 were gradually decreased with increased
      IVD degeneration severity. Interestingly, mRNA expression levels of TNF-alpha and
      IL-6 were significantly upregulated by IL-1beta stimulation. TNF-alpha expression
      in the IL-1beta+Ad 1.0 group was significantly lower than that in the IL-1beta
      group in both NP and AF cells (P < 0.05). Finally, IL-6 expression was not
      affected by adiponectin treatment in IVD cells. CONCLUSIONS: This study
      investigated for the first time the expression of adiponectin receptors in human
      and rat IVD cells. The findings indicate that adiponectin produced by the
      systemic or epidural adipose tissue may be involved in the pathomechanism of IVD
      degeneration.

PMID- 27876066
TI  - In vivo cardiovascular magnetic resonance of 2D vessel wall diffusion anisotropy
      in carotid arteries.
AB  - BACKGROUND: Diffusion weighted (DW) cardiovascular magnetic resonance (CMR) has
      shown great potential to discriminate between healthy and diseased vessel tissue
      by evaluating the apparent diffusion coefficient (ADC) along the arterial axis.
      Recently, ex vivo studies on porcine arteries utilizing diffusion tensor imaging
      (DTI) revealed a circumferential fiber orientation rather than an organization in
      axial direction, suggesting dominant diffusion perpendicular to the slice
      direction. In the present study, we propose a method to access tangential and
      radial diffusion of carotids in vivo by utilizing a pulse sequence that enables
      high resolution DW imaging in combination with a two-dimensional (2D) diffusion
      gradient direction sampling scheme perpendicular to the longitudinal axis of the
      artery. METHODS: High resolution DTI of 12 healthy male volunteers (age: 25-60
      years) was performed on one selected axial slice using a read-out segmented EPI
      (rs-EPI) sequence on a 3T MR scanner. RESULTS: It was found consistently for all
      12 volunteers, that the tangential component as the principle direction of
      diffusion. Mean vessel wall fractional anisotropy (FA) values ranged from 0.7 for
      the youngest to 0.56 for the oldest participant. Linear regression analysis
      between the FA values and volunteers age revealed a highly significant (P < 0.01)
      linear relationship with an adjusted R2 of 0.52. In addition, a linear trend (P <
      0.1) could be observed between radial diffusivity (RD) and age. CONCLUSION: These
      results point to FA being a sensitive parameter able to capture changes in the
      vascular architecture with age. In detail, the data demonstrate a decrease in FA
      with advancing age indicating possible alterations of tissue microstructural
      integrity. Moreover, analyzing 2D diffusion tensor directions is sufficient and
      applicable in a clinical setup concerning the overall scan time.

PMID- 27876068
TI  - Erratum to: Comparison of radiological spino-pelvic sagittal parameters in skiers
      and non-athletes.

PMID- 27876067
TI  - Correlation between clinical and MRI assessment of depth of invasion in oral
      tongue squamous cell carcinoma.
AB  - BACKGROUND: Neck metastasis is the most important prognostic factor in oral
      cavity squamous cell carcinomas (SCC). Apart from the T- stage, depth of invasion
      has been used as a highly predictable factor for microscopic neck metastasis,
      despite the controversy on the exact depth cut off point. Depth of invasion can
      be determined clinically and radio logically. However, there is no standard tool
      to determine depth of invasion preoperatively. Although MRI is used widely to
      stage the head and neck disease, its utility in depth evaluation has not formally
      been assessed. OBJECTIVE: To compare preoperative clinical and radiological depth
      evaluation in oral tongue SCC using the standard pathological depth. To compare
      clinical and radiological accuracy between superficial (<5 mm) vs. deep invaded
      tumor (>=5 mm) METHODS: This prospective study used consecutive biopsy-proven
      oral tongue invasive SCC that presented to the University health network (UHN),
      Toronto. Clinical examination, radiological scan and appropriate staging were
      determined preoperatively. Standard pathology reports postoperatively were
      reviewed to determine the depth of invasion from the tumor specimen. RESULTS: 72
      tumour samples were available for analysis and 53 patients were included. For all
      tumors, both clinical depth (r = 0.779; p < 0.001) and radiographic depth (r
      =0.907; p <0.001) correlated well with pathological depth, with radiographic
      depth correlating slightly better. Clinical depth also correlated well with
      radiographic depth (r = 0.731; p < 0.001). By contrast, for superficial tumors
      (less than 5 mm on pathological measurement) neither clinical (r = 0.333, p =
      0.34) nor radiographic examination (r = - 0.211; p = 0.56) correlated with
      pathological depth of invasion. CONCLUSION: This is the first study evaluating
      the clinical assessment of tumor thickness in comparison to radiographic
      interpretation in oral cavity cancer. There are strong correlations between
      pathological, radiological, and clinical measurements in deep tumors (>=5 mm). In
      superficial tumors (<5 mm), clinical and radiological examination had low
      correlation with pathological thickness.

PMID- 27876069
TI  - MGDG extracted from spinach enhances the cytotoxicity of radiation in pancreatic
      cancer cells.
AB  - BACKGROUND: In our previous study, monogalactosyl diacylglycerol (MGDG) purified
      from spinach was found to have cytotoxic effects in human cancer cell lines. This
      study further assessed whether MGDG can enhance the cytotoxic effects of
      radiation in human pancreatic cancer cells in vitro and in vivo. METHODS:
      Glycoglycerolipids from spinach including MGDG were extracted from dried spinach.
      The cytotoxicity of MGDG were evaluated by the MTT assay using four human
      pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal
      human dermal fibroblasts (NHDFs). The effects of radiation and MGDG alone or in
      combination in MIAPaCa-2 cells was analyzed with the colony forming and apoptosis
      assays, western blotting and cell cycle and DNA damage analyses (gamma-H2AX foci
      staining and comet assay). The inhibitory effects on tumor growth were assessed
      in a mouse xenograft tumor model. RESULTS: MGDG showed dose- and time-dependent
      cytotoxicity, with half-maximal inhibitory concentrations (IC50) in PANC-1, BxPC
      3, MIAPaCa-2 and AsPC-1 cells at 72 h of 25.6 +/- 2.5, 26.9 +/- 1.3, 18.5 +/-
      1.7, and 22.7 +/- 1.9 MUM, respectively. The colony forming assay revealed fewer
      MIAPaCa-2, BxPC-3 and AsPC-1 cell colonies upon treatment with both MGDG and
      radiation as compared to irradiation alone (P < 0.05). The combination of MGDG
      and radiation induced a higher proportion of apoptosis in MIAPaCa-2 cells; this
      effect was associated with increased mitochondrial release of cytochrome c and
      activation of cleaved poly (ADP-ribose) polymerase and caspase-3. DNA damage was
      detected and DNA repair mechanisms were more frequently impaired in cells
      receiving the combination treatment as compared to either one alone. Tumor growth
      was inhibited to a greater degree in mice treated by intratumoral injection of
      MGDG combined with irradiation as compared to either one alone (P < 0.05).
      CONCLUSIONS: This is the first report demonstrating that MGDG enhances the
      cytotoxicity of radiation to induce apoptosis of cancer cells in vitro and in
      vivo. Our findings indicate that this therapeutic combination can be an effective
      strategy for the treatment of pancreatic cancer.

PMID- 27876070
TI  - Ovarian thecoma-fibroma groups: clinical and sonographic features with
      pathological comparison.
AB  - BACKGROUND: Ovarian thecoma-fibroma groups (OTFG) are uncommon sex cord-stromal
      neoplasms. The objective of the study was to demonstrate clinical and sonographic
      features of OTFG and compare with surgical histopathology. METHODS: A total of 61
      patients with surgically proven OTFG were enrolled in this retrospective study to
      demonstrate its clinical and sonographic features and to compare with
      pathological findings. Gray scale and color Doppler sonography were performed
      presurgically with either transabdominal or transvaginal approach to image pelvic
      structures and lesions. The clinical findings and sonographic appearances were
      compared with the types of the OTFG tumors based on the histopathological
      diagnosis. RESULTS: The mean patient age was 53.57 (range, 26-86) years. There
      were 63.93% (39/61) patients in postmenopausal and 63.93% (39/61) patients with
      no clinical symptoms. Ultrasound findings of OTFG revealed as solid tumors with a
      typical feature of well-demarcated hypoechoic masses in 70.49% (43/61), among
      which 74.41% (32/43) tumors were smaller than 5 cm in diameter. There were 17
      mixed echogenic masses with calcification, hemorrhage, or cyst, among which
      70.59% (12/17) lesions were larger than 5 cm in diameter. Acoustic attenuation of
      the tumor was presented in 44.26% (27/61) of the cases. Doppler flow signals
      within the tumors were found in 20 cases (32.79%), in which 80% (16/20) had
      minimal or moderate flow signals. Ascites was detected in 32.79% (20/61) of the
      cases, Megi's syndrome was found in 1 case. Final pathology revealed 41 (67.21%)
      thecoma-fibromas, 15 (24.59%) fibromas, 4 (6.56%) thecomas and 1 (1.64%)
      fibrosarcoma. There were 58 patients underwent cancer antigen 125 (CA125) test,
      and 20.69% (12/58) showed an elevated level. The diameter of tumors was found to
      be significantly correlated with CA125 level (p < 0.01) and the amount of ascites
      fluid (p < 0.05). CONCLUSIONS: The typical sonographic features of OTFG include
      adnexal hypoechoic masses with clear border and acoustic attenuation as well as
      minimal Doppler flow signals. All the aforementioned features could make
      ultrasound imaging as a assistent tool improve the preoperative diagnostic
      accuracy.

PMID- 27876071
TI  - Bilateral single-port thoracoscopic extended thymectomy for management of thymoma
      and myasthenia gravis: case report.
AB  - BACKGROUND: Video-assisted thoracoscopy is become a widely accepted approach for
      the resection of anterior mediastinal masses, including thymoma. The current
      trend is to reduce the number of ports and minimize the length of incisions to
      further decrease postoperative pain, chest wall paresthesia, and length of
      hospitalization. Herein, we reported an extended resection of thymoma in a
      patient with myasthenia gravis through an uniportal bilateral thoracoscopic
      approach. CASE PRESENTATION: A 74 years old woman with myasthenia gravis was
      referred to our attention for management of a 3.5 cm, well capsulate, thymoma.
      All laboratory and cardio-pulmonary tests were within normal; thus, she was
      scheduled for thymoma resection through an uniportal bilateral thoracoscopic
      approach. Under general anaesthesia and selective intubation, the patient was
      placed in a 60 degrees  right lateral decubitus. A 3 cm skin incision was
      performed in the fourth right intercostal space and, through that a 30 degrees 
      video-camera and working instruments were inserted without rib spreading. After
      complete dissection of the thymus and mediastinal fat, the contralateral pleura
      was opened, and, through that the specimen was pushed into the left pleural
      cavity. Then, the patient was placed in the left lateral decubitus. Similarly to
      the right side procedure, a 3-cm incision was performed in the fourth left
      intercostal space to complete thymic dissection and retrieve the specimen. No
      intraoperative and post-operative complications were found. The patient was
      discharged four days later. Pathological examination revealed a type A thymoma
      (Masaoka stage I). No recurrence was found at 18 months of follow-up CONCLUSIONS:
      Bilateral single-port thoracoscopy is an available procedure for management of
      thymoma associated with myasthenia gravis. The less post-operative pain, the
      reduction of hospital stay and the better esthetic results are all potential
      advantages of this approach over traditional technique. Obviously, our impression
      should be validated by larger studies in terms of long-term oncological outcomes.

PMID- 27876073
TI  - Multiple-locus variable-number tandem repeat analysis potentially reveals the
      existence of two groups of Anaplasma phagocytophilum circulating in cattle in
      France with different wild reservoirs.
AB  - BACKGROUND: Anaplasma phagocytophilum is the causative agent of tick-borne fever,
      a disease with high economic impact for domestic ruminants in Europe.
      Epidemiological cycles of this species are complex, and involve different
      ecotypes circulating in various host species. To date, these epidemiological
      cycles are poorly understood, especially in Europe, as European reservoir hosts
      (i.e. vertebrate hosts enabling long-term maintenance of the bacterium in the
      ecosystem), of the bacterium have not yet been clearly identified. In this study,
      our objective was to explore the presence, the prevalence, and the genetic
      diversity of A. phagocytophilum in wild animals, in order to better understand
      their implications as reservoir hosts of this pathogen. METHODS: The spleens of
      101 wild animals were collected from central France and tested for the presence
      of A. phagocytophilum DNA by msp2 qPCR. Positive samples were then typed by multi
      locus variable-number tandem repeat (VNTR) analysis (MLVA), and compared to 179
      previously typed A. phagocytophilum samples. RESULTS: Anaplasma phagocytophilum
      DNA was detected in 82/101 (81.2%) animals including 48/49 red deer (98%), 20/21
      roe deer (95.2%), 13/29 wild boars (44.8%), and 1/1 red fox. MLVA enabled the
      discrimination of two A. phagocytophilum groups: group A contained the majority
      of A. phagocytophilum from red deer and two thirds of those from cattle, while
      group B included a human strain and variants from diverse animal species, i.e.
      sheep, dogs, a horse, the majority of variants from roe deer, and the remaining
      variants from cattle and red deer. CONCLUSIONS: Our results suggest that red deer
      and roe deer are promising A. phagocytophilum reservoir host candidates.
      Moreover, we also showed that A. phagocytophilum potentially circulates in at
      least two epidemiological cycles in French cattle. The first cycle may involve
      red deer as reservoir hosts and cattle as accidental hosts for Group A strains,
      whereas the second cycle could involve roe deer as reservoir hosts and at least
      domestic ruminants, dogs, horses, and humans as accidental hosts for Group B
      strains.

PMID- 27876072
TI  - High-specificity bioinformatics framework for epigenomic profiling of discordant
      twins reveals specific and shared markers for ACPA and ACPA-positive rheumatoid
      arthritis.
AB  - BACKGROUND: Twin studies are powerful models to elucidate epigenetic
      modifications resulting from gene-environment interactions. Yet, commonly a
      limited number of clinical twin samples are available, leading to an underpowered
      situation afflicted with false positives and hampered by low sensitivity. We
      investigated genome-wide DNA methylation data from two small sets of monozygotic
      twins representing different phases during the progression of rheumatoid
      arthritis (RA) to find novel genes for further research. METHODS: We implemented
      a robust statistical methodology aimed at investigating a small number of samples
      to identify differential methylation utilizing the comprehensive CHARM platform
      with whole blood cell DNA from two sets of twin pairs discordant either for ACPA
      (antibodies to citrullinated protein antigens)-positive RA versus ACPA-negative
      healthy or for ACPA-positive healthy (a pre-RA stage) versus ACPA-negative
      healthy. To deconvolute cell type-dependent differential methylation, we assayed
      the methylation patterns of sorted cells and used computational algorithms to
      resolve the relative contributions of different cell types and used them as
      covariates. RESULTS: To identify methylation biomarkers, five healthy twin pairs
      discordant for ACPAs were profiled, revealing a single differentially methylated
      region (DMR). Seven twin pairs discordant for ACPA-positive RA revealed six
      significant DMRs. After deconvolution of cell type proportions, profiling of the
      healthy ACPA discordant twin-set revealed 17 genome-wide significant DMRs. When
      methylation profiles of ACPA-positive RA twin pairs were adjusted for cell type,
      the analysis disclosed one significant DMR, associated with the EXOSC1 gene.
      Additionally, the results from our methodology suggest a temporal connection of
      the protocadherine beta-14 gene to ACPA-positivity with clinical RA. CONCLUSIONS:
      Our biostatistical methodology, optimized for a low-sample twin design, revealed
      non-genetically linked genes associated with two distinct phases of RA.
      Functional evidence is still lacking but the results reinforce further study of
      epigenetic modifications influencing the progression of RA. Our study design and
      methodology may prove generally useful in twin studies.

PMID- 27876074
TI  - Combined detection of serum CTX-II and COMP concentrations in osteoarthritis
      model rabbits: an effective technique for early diagnosis and estimation of
      disease severity.
AB  - BACKGROUND: Early diagnosis of osteoarthritis (OA) is difficult. Cartilage
      oligomeric matrix protein (COMP) and crosslinked C-telopeptides of type II
      collagen (CTX-II) are two markers which can potentially predict the destruction
      of articular cartilage of early OA. To comprehensively evaluate the diagnosis
      value of serum COMP and CTX-II markers in OA, the longitudinal and combined
      measurement of serum COMP and CTX-II were performed at different stages of
      pathological process of OA in adult rabbits with OA, compared with the sham
      operated rabbits. METHODS: Thirty-six adult white rabbits were randomly divided
      into two groups, the OA group and the control group (n = 18 per group). OA models
      were established by anterior cruciate ligament transection. Sham operations were
      performed in the control group. Before the surgery and at weeks 2, 4, 6, 8, 10,
      and 12 after surgery, serum CTX-II and COMP concentrations were detected using
      sandwich-ELISA in all rabbits. Three rabbits in each group were killed at weeks
      2, 4, 6, 8, 10, and 12 after surgery, and femoral condyle specimens were
      collected. Histological changes in articular cartilage were evaluated according
      to the Mankin scoring criteria. RESULTS: At each time point, the Mankin scores
      and serum concentrations of CTX-II and COMP were significantly higher in the OA
      group than in the control group. In addition, in the OA group, there was a
      significant relationship between the CTX-II and COMP concentrations and the
      Mankin score. CONCLUSIONS: Early dynamic combined detection of serum CTX-II and
      COMP concentrations is effective for early OA diagnosis and evaluation of OA
      severity.

PMID- 27876075
TI  - Chlorhexidine bathing and health care-associated infections among adult intensive
      care patients: a systematic review and meta-analysis.
AB  - BACKGROUND: Health care-associated infections (HAI) have been shown to increase
      length of stay, the cost of care, and rates of hospital deaths (Kaye and
      Marchaim, J Am Geriatr Soc 62(2):306-11, 2014; Roberts and Scott, Med Care
      48(11):1026-35, 2010; Warren and Quadir, Crit Care Med 34(8):2084-9, 2006;
      Zimlichman and Henderson, JAMA Intern Med 173(22):2039-46, 2013). Importantly,
      infections acquired during a hospital stay have been shown to be preventable
      (Loveday and Wilson, J Hosp Infect 86:S1-70, 2014). In particular, due to more
      invasive procedures, mechanical ventilation, and critical illness, patients cared
      for in the intensive care unit (ICU) are at greater risk of HAI and associated
      poor outcomes. This meta-analysis aims to summarise the effectiveness of
      chlorhexidine (CHG) bathing, in adult intensive care patients, to reduce
      infection. METHODS: A systematic literature search was undertaken to identify
      trials assessing the effectiveness of CHG bathing to reduce risk of infection,
      among adult intensive care patients. Infections included were: bloodstream
      infections; central line-associated bloodstream infections (CLABSI); catheter
      associated urinary tract infections; ventilator-associated pneumonia; methicillin
      resistant Staphylococcus aureus (MRSA); vancomycin-resistant Enterococcus; and
      Clostridium difficile. Summary estimates were calculated as incidence rate ratios
      (IRRs) and 95% confidence/credible intervals. Variation in study designs was
      addressed using hierarchical Bayesian random-effects models. RESULTS: Seventeen
      trials were included in our final analysis: seven of the studies were cluster
      randomised crossover trials, and the remaining studies were before-and-after
      trials. CHG bathing was estimated to reduce the risk of CLABSI by 56% (Bayesian
      random effects IRR = 0.44 (95% credible interval (CrI), 0.26, 0.75)), and MRSA
      colonisation and bacteraemia in the ICU by 41% and 36%, respectively (IRR = 0.59
      (95% CrI, 0.36, 0.94); and IRR = 0.64 (95% CrI, 0.43, 0.91)). The numbers needed
      to treat for these specific ICU infections ranged from 360 (CLABSI) to 2780 (MRSA
      bacteraemia). CONCLUSION: This meta-analysis of the effectiveness of CHG bathing
      to reduce infections among adults in the ICU has found evidence for the benefit
      of daily bathing with CHG to reduce CLABSI and MRSA infections. However, the
      effectiveness may be dependent on the underlying baseline risk of these events
      among the given ICU population. Therefore, CHG bathing appears to be of the most
      clinical benefit when infection rates are high for a given ICU population.

PMID- 27876076
TI  - Bladder outlet obstruction; a rare complication of the neglected schistosome,
      Schistosoma haematobium: two case reports and public health challenges.
AB  - BACKGROUND: Schistosomiasis is a severe parasitic infestation with debilitating
      complications and is the third most devastating tropical disease in the world. It
      is one of the neglected tropical diseases (NTDs) with a high disease-burden. We
      present two rare cases of bladder outlet obstruction: one which led to a chronic
      kidney disease and ultimately death and a second which recovered after treatment
      with praziquantel. CASE PRESENTATIONS: A 72 year old male presented with lower
      urinary tract symptoms which culminated in an episode of acute urinary retention.
      The patient had never received preventive chemotherapy with praziquantel. After
      suprapubic aspiration, the cause of the obstructive uropathy was found to be
      several mature live worms of Schistosoma haematobium. Despite treatment with
      praziquantel and haemodialysis; we lost the patient due to sepsis from a urinary
      tract infection. In the second case, a 15 year old male presented with LUTS for a
      1 year duration and was diagnosed to have schistosomiasis after eggs of
      Schistosoma haematobium were found in his urine. He was treated with
      praziquantel. CONCLUSION: There are several gaps in the public health policies in
      place to control this NTD in Cameroon as annual distribution of preventive
      chemotherapy is inadequate due to inaccessibility of some high-endemic zones and
      is based on data obtained two decades ago. Population education is insufficient
      leading to poor health-seeking behaviour. These gaps in public health policies
      need to be addressed to aid in the overall achievement of the sustainable
      development goals.

PMID- 27876077
TI  - Post-traumatic acute kidney injury: a cross-sectional study of trauma patients.
AB  - BACKGROUND: The causes of post-traumatic acute kidney injury (AKI) are
      multifactorial, and shock associated with major trauma has been proposed to
      result in inadequate renal perfusion and subsequent AKI in trauma patients. This
      study aimed to investigate the true incidence and clinical presentation of post
      traumatic AKI in hospitalized adult patients and its association with shock at a
      Level I trauma center. METHODS: Detailed data of 78 trauma patients with AKI and
      14,504 patients without AKI between January 1, 2009 and December 31, 2014 were
      retrieved from the Trauma Registry System. Patients with direct renal trauma were
      excluded from this study. Two-sided Fisher's exact or Pearson's chi-square tests
      were used to compare categorical data, unpaired Student's t-test was used to
      analyze normally distributed continuous data, and Mann-Whitney's U test was used
      to compare non-normally distributed data. Propensity score matching with a 1:1
      ratio with logistic regression was used to evaluate the effect of shock on AKI.
      RESULTS: Patients with AKI presented with significantly older age, higher
      incidence rates of pre-existing comorbidities, higher odds of associated injures
      (subdural hematoma, intracerebral hematoma, intra-abdominal injury, and hepatic
      injury), and higher injury severity than patients without AKI. In addition,
      patients with AKI had a longer hospital stay (18.3 days vs. 9.8 days,
      respectively; P < 0.001) and intensive care unit (ICU) stay (18.8 days vs. 8.6
      days, respectively; P < 0. 001), higher proportion of admission into the ICU
      (57.7% vs. 19.0%, respectively; P < 0.001), and a higher odds ratio (OR) of short
      term mortality (OR 39.0; 95% confidence interval, 24.59-61.82; P < 0.001).
      However, logistic regression analysis of well-matched pairs after propensity
      score matching did not show a significant influence of shock on the occurrence of
      AKI. DISCUSSION: We believe that early and aggressive resuscitation, to avoid
      prolonged untreated shock, may help to prevent the occurrence of post-traumatic
      AKI. However, more evidence is required to support this observation. CONCLUSION:
      Compared to patients without AKI, patients with AKI presented with different
      injury characteristics and worse outcome. However, an association between shock
      and post-traumatic AKI could not be identified.

PMID- 27876078
TI  - Simultaneous detection and differentiation of three genotypes of Brassica yellows
      virus by multiplex reverse transcription-polymerase chain reaction.
AB  - BACKGROUND: Brassica yellows virus (BrYV), proposed to be a new polerovirus
      species, three distinct genotypes (BrYV-A, BrYV-B and BrYV-C) have been
      described. This study was to develop a simple, rapid, sensitive, cost-effective
      method for simultaneous detection and differentiation of three genotypes of BrYV.
      RESULTS: In this study, a multiplex reverse transcription-polymerase chain
      reaction (mRT-PCR) was developed for simultaneous detection and differentiation
      of the three genotypes of BrYV. The three genotypes of BrYV and Tunip yellows
      virus (TuYV) could be differentiated simultaneously using six optimized specific
      oligonucleotide primers, including one universal primer for detecting BrYV, three
      BrYV genotype-specific primers, and a pair of primers for specific detection of
      TuYV. Primers were designed from conserved regions of each virus and their
      specificity was confirmed by sequencing PCR products. The mRT-PCR products were
      278 bp for BrYV-A, 674 bp for BrYV-B, 505 bp for BrYV-C, and 205 bp for TuYV.
      Amplification of three target genotypes was optimized by increasing the PCR
      annealing temperatures to 62  degrees C. One to three fragments specific for the
      virus genotypes were simultaneously amplified from infected samples and
      identified by their specific molecular sizes in agarose gel electrophoresis. No
      specific products could be amplified from cDNAs of other viruses which could
      infect crucifer crops. Detection limits of the plasmids for multiplex PCR were
      100 fg for BrYV-A and BrYV-B, 10 pg for BrYV-C, and 1 pg for TuYV, respectively.
      The mRT-PCR was applied successfully for detection of three BrYV genotypes from
      field samples collected in China. CONCLUSIONS: The simple, rapid, sensitive, and
      cost-effective mRT-PCR was developed successfully for detection and
      differentiation of the three genotypes of BrYV.

PMID- 27876079
TI  - Copenhagen infant mental health project: study protocol for a randomized
      controlled trial comparing circle of security -parenting and care as usual as
      interventions targeting infant mental health risks.
AB  - BACKGROUND: Infant mental health is a significant public health issue as early
      adversity and exposure to early childhood stress are significant risk factors
      that may have detrimental long-term developmental consequences for the affected
      children. Negative outcomes are seen on a range of areas such as physical and
      mental health, educational and labor market success, social network and
      establishing of family. Secure attachment is associated with optimal outcomes in
      all developmental domains in childhood, and both insecure and disorganized
      attachment are associated with a range of later problems and psychopathologies.
      In disadvantaged populations insecure and disorganized attachment are common,
      which points to the need of identifying early risk and effective methods of
      addressing such problems. This protocol describes an experimental evaluation of
      an indicated group-based parental educational program, Circle of Security
      Parenting (COS-P), currently being conducted in Denmark. METHODS/DESIGN: In a
      parallel randomized controlled trial of two intervention groups this study tests
      the efficacy of COS-P compared to Care as Usual (CAU) in enhancing maternal
      sensitivity and child attachment in a community sample in the City of Copenhagen,
      Denmark. During the project a general population of an estimated 17.600 families
      with an infant aged 2-12 months are screened for two known infant mental health
      risks, maternal postnatal depression and infant social withdrawal. Eligible
      families (N = 314), who agree to participate, will be randomly allocated with a
      ratio of 2:1 into the COS-P intervention arm and into CAU. Data will be obtained
      at inclusion (baseline) and at follow-up when the child is 12-16 months. The
      primary outcome is maternal sensitivity. Secondary outcomes include quality of
      infant attachment, language, cognitive and socioemotional development, family
      functioning, parental stress, parental mentalizing and maternal mental wellbeing.
      DISCUSSION: The potential implications of the experimental evaluation of an
      indicated brief group-based parenting educational program to enhance parental
      sensitivity and attachment are discussed. TRIAL REGISTRATION:
      ClinicalTrials.govID: NCT02497677 . Registered July 15 2015.

PMID- 27876080
TI  - Effect of testosterone on the Connexin37 of sexual mature mouse cumulus oocyte
      complex.
AB  - BACKGROUND: Recent researches demonstrate that pre-treatment with androgen could
      increase retrieved oocytes number and clinical pregnancy rate in poor ovarian
      response (POR) patients. In view of gap junction intercellular communication
      (GJIC) is important for follicular growth, and androgen plays an important role
      in improving prognosis of POR patients, we speculate that androgen can increase
      the expression of connexin in follicle cells, and improve ovarian
      microenvironment, thus can promote ovarian response. The objective of the
      research is to study the effect of testosterone on connexin37 (Cx37) expression
      so as to provide theoretical basis for adding testosterone in treatment of POR.
      METHODS: Cumulus-oocyte-cells (COCs) were collected from ICR mice ovaries, and
      were cultured in vitro for 48 h and then treated with testosterone (T) at various
      concentration. To assess whether the effect of androgen on Cx37 expression is
      mediated through androgen receptor (AR) pathway, COCs were cultured in vitro with
      Flutamide (androgen receptor antagonist). The expression of Cx37 was determined
      by western blot. RESULTS: The expression of Cx37 in COCs which were treated with
      testosterone was higher than that of control group. There were significant
      differences (P < 0.001;<0.001;<0.001;<0.001). Cx37 increased with the elevated
      testosterone concentrations. Cx37 was lower in androgen receptor antagonist group
      (2.57 +/- 0.12) than the corresponding testosterone concentrations group (4.42 +/
      0.28). There were significant differences between two groups (P < 0.001).
      CONCLUSIONS: There was close relationship between gap junction protein and
      ovarian response, which suggested that androgen could promote ovarian response by
      increasing the expression of Cx37 in follicle. Androgen plays an important role
      in ovarian response through the AR pathway and non-AR pathway.

PMID- 27876081
TI  - In vitro activity of ten essential oils against Sarcoptes scabiei.
AB  - BACKGROUND: The development of alternative approaches in ectoparasite management
      is currently required. Essential oils have been demonstrated to exhibit fumigant
      and topical toxicity to a number of arthropods. The aim of the present study was
      to assess the potential efficacy of ten essential oils against Sarcoptes scabiei.
      METHODS: The major chemical components of the oils were identified by GC-MS
      analysis. Contact and fumigation bioassays were performed on Sarcoptes mites
      collected from experimentally infected pigs. For contact bioassays, essential
      oils were diluted with paraffin to get concentrations at 10, 5, and even 1% for
      the most efficient ones. The mites were inspected under a stereomicroscope 10,
      20, 30, 40, 50, 60, 90, 120, 150, and 180min after contact. For fumigation
      bioassay, a filter paper was treated with 100 MUL of the pure essential oil. The
      mites were inspected under a stereomicroscope for the first 5min, and then every
      5min until 1h. RESULTS: Using contact bioassays, 1% clove and palmarosa oil
      killed all the mites within 20 and 50min, respectively. The oils efficacy order
      was: clove > palmarosa > geranium > tea tree > lavender > manuka > bitter orange
      > eucalyptus > Japanese cedar. In fumigation bioassays, the efficacy order was:
      tea tree > clove > eucalyptus > lavender > palmarosa > geranium > Japanese cedar
      > bitter orange > manuka. In both bioassays, cade oil showed no activity.
      CONCLUSION: Essential oils, especially tea tree, clove, palmarosa, and eucalyptus
      oils, are potential complementary or alternative products to treat S. scabiei
      infections in humans or animals, as well as to control the mites in the
      environment.

PMID- 27876082
TI  - Evaluating Data Abstraction Assistant, a novel software application for data
      abstraction during systematic reviews: protocol for a randomized controlled
      trial.
AB  - BACKGROUND: Data abstraction, a critical systematic review step, is time
      consuming and prone to errors. Current standards for approaches to data
      abstraction rest on a weak evidence base. We developed the Data Abstraction
      Assistant (DAA), a novel software application designed to facilitate the
      abstraction process by allowing users to (1) view study article PDFs juxtaposed
      to electronic data abstraction forms linked to a data abstraction system, (2)
      highlight (or "pin") the location of the text in the PDF, and (3) copy relevant
      text from the PDF into the form. We describe the design of a randomized
      controlled trial (RCT) that compares the relative effectiveness of (A) DAA
      facilitated single abstraction plus verification by a second person, (B)
      traditional (non-DAA-facilitated) single abstraction plus verification by a
      second person, and (C) traditional independent dual abstraction plus adjudication
      to ascertain the accuracy and efficiency of abstraction. METHODS: This is an
      online, randomized, three-arm, crossover trial. We will enroll 24 pairs of
      abstractors (i.e., sample size is 48 participants), each pair comprising one less
      and one more experienced abstractor. Pairs will be randomized to abstract data
      from six articles, two under each of the three approaches. Abstractors will
      complete pre-tested data abstraction forms using the Systematic Review Data
      Repository (SRDR), an online data abstraction system. The primary outcomes are
      (1) proportion of data items abstracted that constitute an error (compared with
      an answer key) and (2) total time taken to complete abstraction (by two
      abstractors in the pair, including verification and/or adjudication). DISCUSSION:
      The DAA trial uses a practical design to test a novel software application as a
      tool to help improve the accuracy and efficiency of the data abstraction process
      during systematic reviews. Findings from the DAA trial will provide much-needed
      evidence to strengthen current recommendations for data abstraction approaches.
      TRIAL REGISTRATION: The trial is registered at National Information Center on
      Health Services Research and Health Care Technology (NICHSR) under Registration #
      HSRP20152269:
      https://wwwcf.nlm.nih.gov/hsr_project/view_hsrproj_record.cfm?NLMUNIQUE_ID=201522
      9&SEARCH_FOR=Tianjing%20Li . All items from the World Health Organization Trial
      Registration Data Set are covered at various locations in this protocol. Protocol
      version and date: This is version 2.0 of the protocol, dated September 6, 2016.
      As needed, we will communicate any protocol amendments to the Institutional
      Review Boards (IRBs) of Johns Hopkins Bloomberg School of Public Health (JHBSPH)
      and Brown University. We also will make appropriate as-needed modifications to
      the NICHSR website in a timely fashion.

PMID- 27876083
TI  - Two-year clinical follow-up of the Multicenter Randomized Clinical Trial of
      Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN):
      design and statistical analysis plan of the extended follow-up study.
AB  - BACKGROUND: MR CLEAN was the first randomized trial to demonstrate the short-term
      clinical effectiveness of endovascular treatment in patients with acute ischemic
      stroke caused by large vessel occlusion in the anterior circulation. Several
      other trials confirmed that endovascular treatment improves clinical outcome at
      three months. However, limited data are available on long-term clinical outcome.
      We aimed to estimate the effect of endovascular treatment on functional outcome
      at two-year follow-up in patients with acute ischemic stroke. Secondly, we aimed
      to assess the effect of endovascular treatment on major vascular events and
      mortality during two years of follow-up. METHODS: MR CLEAN is a multicenter
      clinical trial with randomized treatment allocation, open-label treatment, and
      blinded endpoint evaluation. Patients included were 18 years or older with acute
      ischemic stroke caused by a proven anterior proximal artery occlusion who could
      be treated within six hours after stroke onset. The intervention contrast was
      endovascular treatment and usual care versus no endovascular treatment and usual
      care. The current study extended the follow-up duration from three months to two
      years. The primary outcome is the score on the modified Rankin scale at two
      years. Secondary outcomes include all-cause mortality and the occurrence of major
      vascular events within two years of follow-up. DISCUSSION: The results of our
      study provide information on the long-term clinical effectiveness of endovascular
      treatment, which may have implications for individual treatment decisions and
      estimates of cost-effectiveness. TRIAL REGISTRATION: NTR1804 . Registered on 7
      May 2009; ISRCTN10888758 . Registered on 24 July 2012 (main MR CLEAN trial);
      NTR5073 . Registered on 26 February 2015 (extended follow-up study).

PMID- 27876085
TI  - Onychomycosis in diabetic patients in Fako Division of Cameroon: prevalence,
      causative agents, associated factors and antifungal sensitivity patterns.
AB  - BACKGROUND: Onychomycosis is an infection of the nail unit by a fungus. This is a
      very common infection amongst diabetics. Its occurrence among diabetics in Fako
      division is unknown. In this study we provide information on the characteristics
      of onychomycosis in diabetics in Fako division, Cameroon. METHODS: A cross
      sectional descriptive and analytical hospital-based study was conducted in two
      diabetic clinics in the Buea and Limbe regional hospitals. We recruited 152
      consenting diabetics into the study. Demographic, behavioural, and clinical data
      of patients were obtained through the use of structured questionnaires. Toenail,
      finger nail, skin scrapings and nail clippings were collected from participants,
      KOH mounts were prepared and observed under the microscope and cultured on
      Sabouraud Dextrose Agar supplemented with chloramphenicol to isolate causative
      fungi. Identification of isolates was done to species level using the cello tape
      flag method and slide culture. The presence of a dermatophyte by either
      microscopy or culture or both methods was considered positive for onychomycosis.
      Antifungal susceptibility testing was carried out using selected antifungals by
      the Kirby-Bauer disk diffusion method on Sabouraud Dextrose Agar. RESULTS:
      Clinical onychomycosis was found in 77 of the 152 diabetics tested giving a
      prevalence of 50.7% (95% CI 42.4-58.9) in diabetics in Fako. No socio-demographic
      or clinical factor studied was significantly associated with onychomycosis.
      Trichophyton rubrum was the most common isolate (62%). Other isolates included
      Trichophyton metagraphyte (22%) and Trichophyton tonsurans (16%). Dermatophytes
      were sensitive to miconazole (66%), amphotericin B (19%) and ketoconazole (14%).
      CONCLUSION: Onychomycosis is common in diabetics in Fako signifying the need for
      regular screening by either microscopy or culture. Infected nails could be
      treated with miconazole.

PMID- 27876086
TI  - Suprascapular neuropathy in the setting of rotator cuff tears: study protocol for
      a double-blinded randomized controlled trial.
AB  - BACKGROUND: It has been indicated that rotator cuff tears, especially large or
      massive ones, can cause suprascapular neuropathy. When such a diagnosis has been
      established, it is still unknown whether an arthroscopic release of the superior
      transverse scapular ligament during cuff repair can change the course of this
      neuropathy. METHODS/DESIGN: This is a single-center, double-blinded randomized
      controlled trial for which 42 patients with large or massive repairable rotator
      cuff tears and suprascapular neuropathy will be recruited and followed up at 6
      and 12 months. Nerve function will be measured by nerve conduction and
      electromyography studies preoperatively and at the selected follow-up periods.
      Patients will be randomly divided into equally numbered groups, the first one
      being the control group. Patients of this group will undergo arthroscopic repair
      of the rotator cuff without combined arthroscopic release of the superior
      transverse scapular ligament; in the second group the ligament will be released.
      The primary objective is to test the null hypothesis that arthroscopic repair of
      large/massive rotator cuff tears in patients with combined suprascapular
      neuropathy provides equivalent outcomes to one-stage arthroscopic cuff repair
      where the superior suprascapular ligament is additionally released. The secondary
      objective is to search for a relation between rotator cuff tear size and degree
      of suprascapular nerve recovery. The tertiary objective is to demonstrate any
      relation between rotator cuff muscle fatty infiltration grade and degree of
      suprascapular nerve function. Patients, clinicians during follow-up clinics and
      the neurologist will be blinded to the type of surgery performed. DISCUSSION: To
      the best of our knowledge, we are unaware of any prospective, randomized double
      blinded studies with similar objectives. So far, the evidence suggests a positive
      correlation between massive rotator cuff tears and suprascapular neuropathy.
      However, there is mixed evidence suggesting that neuropathy can be effectively
      treated with rotator cuff repair with or without release of the superior
      transverse scapular ligament. TRIAL REGISTRATION: ClinicalTrials.gov registration
      number NCT02318381 ; date of initial release: 5 December 2014.

PMID- 27876084
TI  - A trial to determine whether septic shock-reversal is quicker in pediatric
      patients randomized to an early goal-directed fluid-sparing strategy versus usual
      care (SQUEEZE): study protocol for a pilot randomized controlled trial.
AB  - BACKGROUND: Current pediatric septic shock resuscitation guidelines from the
      American College of Critical Care Medicine focus on the early and goal-directed
      administration of intravascular fluid followed by vasoactive medication infusions
      for persistent and fluid-refractory shock. However, accumulating adult and
      pediatric data suggest that excessive fluid administration is associated with
      worse patient outcomes and even increased risk of death. The optimal amount of
      intravascular fluid required in early pediatric septic shock resuscitation prior
      to the initiation of vasoactive support remains unanswered. METHODS/DESIGN: The
      SQUEEZE Pilot Trial is a pragmatic, two-arm, parallel-group, open-label,
      prospective pilot randomized controlled trial. Participants are children aged 29
      days to under 18 years with suspected or confirmed septic shock and a need for
      ongoing resuscitation. Eligible participants are enrolled under an exception to
      consent process and randomly assigned via concealed allocation to either the
      Usual Care (control) or Fluid Sparing (intervention) resuscitation strategy. The
      primary objective of this pilot trial is to determine feasibility, based on the
      ability to enroll participants and to adhere to the study protocol. The primary
      outcome measure by which success will be determined is participant enrollment
      rate ("pass" defined as at least two participants/site/month, recognizing that
      enrollment may be slower during the run-in phase). Secondary objectives include
      assessing (1) appropriateness of eligibility criteria, and (2) completeness of
      clinical outcomes to inform the endpoints for the planned multisite trial. To
      support the nested translational study, SQUEEZE-D, we will also evaluate the
      feasibility of describing cell-free DNA (a procoagulant molecule with prognostic
      utility) in blood samples obtained from children enrolled into the SQUEEZE Pilot
      Trial at baseline and at 24 h. DISCUSSION: The optimal degree of fluid
      resuscitation and the timing of initiation of vasoactive support in order to
      achieve recommended therapeutic targets in children with septic shock remains
      unanswered. No prospective study to date has examined this important question for
      children in developed countries including Canada. Recruitment for the SQUEEZE
      Pilot Trial opened on 6 January 2014. Findings will inform the feasibility of the
      planned multicenter trial to answer our overall research question. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier NCT01973907 , registered on 23
      October 2013.

PMID- 27876088
TI  - Erratum to: Illuminating uveitis: metagenomic deep sequencing identifies common
      and rare pathogens.

PMID- 27876087
TI  - Heterogeneity in the abundance and distribution of Ixodes ricinus and Borrelia
      burgdorferi (sensu lato) in Scotland: implications for risk prediction.
AB  - BACKGROUND: Cases of Lyme borreliosis, a vector-borne zoonosis caused by bacteria
      in the Borrelia burgdorferi (sensu lato) species group, have increased in recent
      years in Europe. Knowledge of environmental factors associated with abundance of
      the tick vector Ixodes ricinus and the pathogen B. burgdorferi (s.l.) is of
      interest to understand responses to environmental changes, predict variation in
      risk and to inform management interventions. METHODS: Nineteen woodland sites
      across Scotland were surveyed in 2012 for B. burgdorferi (s.l.) infection in
      questing I. ricinus nymphs (n = 200 per site), deer abundance and vegetation.
      Climatic factors were extracted for each site. Six additional sites were surveyed
      for questing nymphs in both 2012 and 2013 (n = 200 per site and year) to test for
      variation in B. burgdorferi (s.l.) prevalence between years. RESULTS: The mean
      prevalence of B. burgdorferi (s.l.) across 19 sites was 1.7% (95% CI: 1.4-2.2%;
      range 0-6%), all four genospecies known to be present in the UK were detected: B.
      garinii, B. afzelii, B. burgdorferi (sensu stricto) and B. valaisiana. A higher
      prevalence of B. burgdorferi (s.l.), higher densities of nymphs and higher
      densities of infected nymphs were found at sites with warmer climates, estimated
      with growing degree-days. No association between infection prevalence in nymphs
      and woodland type (semi-natural mixed vs coniferous) or deer density was found.
      At six sites sampled in 2012 and 2013, there was a significant increase in B.
      afzelli prevalence at two sites and a decrease in B. garinii prevalence at one
      site. CONCLUSIONS: This study highlights challenges for the prediction of risk of
      Lyme borreliosis, reflecting the sensitivity of both pathogen and vector ecology
      to habitat, host and climatic factors. Significant changes in the prevalence of
      individual genospecies at sites monitored across time are likely to be due to
      variability in the host community composition between years. Our results indicate
      the importance of monitoring dynamic variables such as reservoir host populations
      as well as climate and habitat factors over multiple years, to identify
      environmental factors associated with Lyme borreliosis risk.

PMID- 27876089
TI  - Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, autonomic
      dysregulation and neuroendocrine tumor syndrome with a homogenous enlargement of
      the pituitary gland: a case report.
AB  - BACKGROUND: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction,
      and autonomic dysregulation syndrome is a rare pediatric disorder with a variable
      sequence of clinical presentations, undefined etiology, and high risk of
      mortality. Our patient presented an unusual course of the disease accompanied by
      a homogenous mild enlargement of her pituitary gland with an intact pituitary
      endocrine axis which, to the best of our knowledge, represents a new finding in
      rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic
      dysregulation syndrome. CASE PRESENTATION: We present a documented case of a 4
      years and 8-month-old Syrian Arabic girl with a distinctive course of signs and
      symptoms of rapid-onset obesity with hypoventilation, hypothalamic dysfunction,
      and autonomic dysregulation syndrome accompanied by mature ganglioneuroma in her
      chest, a homogenous mild enlargement of her pituitary gland, generalized cortical
      brain atrophy, and seizures. Three months after her first marked symptoms were
      noted she had a sudden progression of severe respiratory distress that ended with
      her death. CONCLUSIONS: The findings of this case could increase our
      understanding of the pathogenetic mechanisms of rapid-onset obesity with
      hypoventilation, hypothalamic dysfunction, and autonomic dysregulation, and place
      more emphases on pediatricians to consider rapid-onset obesity with
      hypoventilation, hypothalamic dysfunction, and autonomic dysregulation syndrome
      whenever early rapid onset of obesity, associated with any malfunction, is
      observed in children. This knowledge could be lifesaving for children with rapid
      onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic
      dysregulation syndrome.

PMID- 27876090
TI  - The impact of household wealth on child survival in Ghana.
AB  - BACKGROUND: Improving child health is one of the major policy agendas for most of
      the governments, especially in the developing countries. These governments have
      been implementing various strategies such as improving healthcare financing,
      improving access to health, increasing educational level, and income level of the
      household to improve child health. Despite all these efforts, under-five and
      infant mortality rates remain high in many developing nations. Some previous
      studies examined how economic development or household's economic condition
      contributes to child survival in developing countries. In Ghana, the question as
      to what extent does economic circumstances of households reduces infant and child
      mortality still remain largely unanswered. Thus, the purpose of this study is to
      investigate the extent to which wealth affects the survival of under-five
      children, using data from the Demographic and Health Survey (DHS) of Ghana.
      METHODS: In this study, we use four waves of data from Demographic and Health
      Surveys (DHS) of Ghana from 1993 to 2008. The DHS is a detailed data set that
      provides comprehensive information on households and their demographic
      characteristics in Ghana. Data was obtained by distributing questionnaires to
      women (from 6000 households) of reproductive age between 15 and 49 years, which
      asked, among other things, their birth history information. The Weibull hazard
      model with gamma frailty was used to estimate wealth effect, as well as the trend
      of wealth effect on child's survival probability. RESULTS: We find that household
      wealth status has a significant effect on the child survival in Ghana. A child is
      more likely to survive when he/she is from a household with high wealth status.
      Among other factors, birth spacing and parental education were found to be highly
      significant to increase a child's survival probability. CONCLUSIONS: Our findings
      offer plausible mechanisms for the association of household wealth and child
      survival. We therefore suggest that the Government of Ghana strengthens and
      sustains improved livelihood programs, which reduce poverty. They should also
      take further initiatives that will increase adult education and improve health
      knowledge. To the best of our knowledge, this is the first study in Ghana that
      combines four cross sectional data sets from DHS to study a policy-relevant
      question. We extend Standard Weibull hazard model into Weibull hazard model with
      gamma frailty, which gives us a more accurate estimation. Finally, the findings
      of this study are of interest not only because they provide insights into the
      determinants of child health in Ghana and other developing countries, but they
      also suggest policies beyond the scope of health.

PMID- 27876091
TI  - Symmetrical acrokeratoderma: a case series in Indian patients.
AB  - : Symmetrical acrokeratoderma is a recently described dermatosis in young adult
      males of Chinese descent. In this report, we describe a series of five cases of
      symmetrical acrokeratoderma from India. All 5 patients had asymptomatic, brownish
      black plaques distributed symmetrically over dorsum of hand and feet with
      variable involvement of wrist, flexural surface of forearm, elbow, ankles, shin
      and knee joint. Palms and soles were characteristically spared. Typically whitish
      maceration of the lesions was seen after immersing in water. The disease showed
      exacerbation in hot and humid climate with spontaneous resolution in winter.
      Histopathological examination showed basket weave hyperkeratosis, irregular
      acanthosis and mild peri-vascular lymphomononuclear infiltrate. Loosening of the
      stratum corneum was seen in post-immersion biopsy specimens. Acitretin appeared
      to provide symptomatic improvement in the short term without any long-term effect
      on the natural disease course. The genetic and environmental factors involved in
      disease causation needs to be elucidated in future. TRIAL REGISTRATION: The study
      was not registered in a trial registry since it was a retrospective analysis of
      the clinical records and not an interventional/observational study.

PMID- 27876092
TI  - Assessing the validity of abbreviated literature searches for rapid reviews:
      protocol of a non-inferiority and meta-epidemiologic study.
AB  - BACKGROUND: Systematic reviews offer the most reliable and valid support for
      health policy decision-making, patient information, and guideline development.
      However, they are labor intensive and frequently take longer than 1 year to
      complete. Consequently, they often do not meet the needs of those who need to
      make decisions quickly. Rapid reviews have therefore become a pragmatic
      alternative to systematic reviews. They are knowledge syntheses that abbreviate
      certain methodological aspects of systematic reviews to produce information more
      quickly. Methodological shortcuts often take place in literature identification.
      A potential drawback is less reliable results. To date, the impact of abbreviated
      searches on estimates of treatment effects and subsequent conclusions has not
      been analyzed systematically across multiple bodies of evidence. We aim to answer
      the research question: Do bodies of evidence that are based on abbreviated
      literature searches lead to different conclusions about benefits and harms of
      interventions compared with bodies of evidence that are based on comprehensive,
      systematic literature searches? METHODS: We will use a non-inferiority and meta
      epidemiologic design. The primary outcome is the proportion of discordant
      conclusions based on different search approaches. Drawing of a pool of Cochrane
      reports published between 2012 and 2016, we will randomly select 60 reports.
      Eligible reports are those that present a summary-of-findings table, draw a clear
      conclusion, present data for meta-analyses, and document the search strategy
      clearly. We will conduct several abbreviated searches to detect whether included
      studies in these Cochrane reviews could be detected. If searches could not detect
      all studies, we will revise the original summary-of-findings table and ask review
      authors whether the missed evidence would change conclusions of their report. We
      will determine the proportion of discordant conclusions for each abbreviated
      search approach. We will consider an abbreviated search as non-inferior if the
      lower limit of the 95% confidence interval of the proportion of discordant
      conclusions is below the non-inferiority margin, which is determined based on
      results of a survey for clinical and public health scenarios. DISCUSSION: This
      will be the first study to assess whether the reduced sensitivity of abbreviated
      searches has an impact on conclusions across multiple bodies of evidence, not
      only on effect estimates.

PMID- 27876095
TI  - Asymmetric hybridization between non-native winter moth, Operophtera brumata
      (Lepidoptera: Geometridae), and native Bruce spanworm, Operophtera bruceata, in
      the Northeastern United States, assessed with novel microsatellites and SNPs.
AB  - The European winter moth, Operophtera brumata, is a non-native pest in the
      Northeastern USA causing defoliation of forest trees and crops such as apples and
      blueberries. This species is known to hybridize with O. bruceata, the Bruce
      spanworm, a native species across North America, although it is not known if
      there are hybrid generations beyond F1. To study winter moth population genetics
      and hybridization with Bruce spanworm, we developed two sets of genetic markers,
      single nucleotide polymorphisms (SNPs) and microsatellites, using genomic
      approaches. Both types of markers were validated using samples from the two
      species and their hybrids. We identified 1216 SNPs and 24 variable microsatellite
      loci. From them we developed a subset of 95 species-diagnostic SNPs and ten
      microsatellite loci that could be used for hybrid identification. We further
      validated the ten microsatellite loci by screening field collected samples of
      both species and putative hybrids. In addition to confirming the presence of F1
      hybrids reported in previous studies, we found evidence for multi-generation
      asymmetric hybridization, as suggested by the occurrence of hybrid backcrosses
      with the winter month, but not with the Bruce spanworm. Laboratory crosses
      between winter moth females and Bruce spanworm males resulted in a higher
      proportion of viable eggs than the reciprocal cross, supporting this pattern. We
      discuss the possible roles of population demographics, sex chromosome genetic
      incompatibility, and bacterial symbionts as causes of this asymmetrical
      hybridization and the utility of the developed markers for future studies.

PMID- 27876094
TI  - Nitric oxide has contrasting age-dependent effects on the functionality of murine
      hematopoietic stem cells.
AB  - BACKGROUND: The success of hematopoietic stem cell (HSC) transplantation is
      dependent on the quality of the donor HSCs. Some sources of HSCs display reduced
      engraftment efficiency either because of inadequate number (e.g., fetal liver and
      cord blood), or age-related dysfunction (e.g. in older individuals). Therefore,
      use of pharmacological compounds to improve functionality of HSCs is a forefront
      research area in hematology. METHODS: Lineage negative (Lin-) cells isolated from
      murine bone marrow or sort-purified Lin-Sca-1+c-Kit+CD34- (LSK-CD34-) were
      treated with a nitric oxide donor, sodium nitroprusside (SNP). The cells were
      subjected to various phenotypic and functional assays. RESULTS: We found that SNP
      treatment of Lin- cells leads to an increase in the numbers of LSK-CD34+ cells in
      them. Using sort-purified LSK CD34- HSCs, we show that this is related to
      acquisition of CD34 expression by LSK-CD34- cells, rather than proliferation of
      LSK-CD34+ cells. Most importantly, this upregulated expression of CD34 had age
      dependent contrasting effects on HSC functionality. Increased CD34 expression
      significantly improved the engraftment of juvenile HSCs (6-8 weeks); in sharp
      contrast, it reduced the engraftment of adult HSCs (10-12 weeks). The molecular
      mechanism behind this phenomenon involved nitric oxide (NO)-mediated differential
      induction of various transcription factors involved in commitment with regard to
      self-renewal in adult and juvenile HSCs, respectively. Preliminary experiments
      performed on cord blood-derived and mobilized peripheral blood-derived cells
      revealed that NO exerts age-dependent contrasting effects on human HSCs as well.
      CONCLUSIONS: This study demonstrates novel age-dependent contrasting effects of
      NO on HSC functionality and suggests that HSC age may be an important parameter
      in screening of various compounds for their use in manipulation of HSCs.

PMID- 27876093
TI  - Involvement of hepatic macrophages in the antifibrotic effect of IGF-I
      overexpressing mesenchymal stromal cells.
AB  - BACKGROUND: Cirrhosis is a major health problem worldwide and new therapies are
      needed. Hepatic macrophages (hMo) have a pivotal role in liver fibrosis, being
      able to act in both its promotion and its resolution. It is well-known that
      mesenchymal stromal cells (MSCs) can modulate the immune/inflammatory cells.
      However, the effects of MSCs over hMo in the context of liver fibrosis remain
      unclear. We previously described evidence of the antifibrotic effects of in vivo
      applying MSCs, which were enhanced by forced overexpression of insulin-like
      growth factor 1 (AdIGF-I-MSCs). The aim of this work was to analyze the effect of
      MSCs on hMo behavior in the context of liver fibrosis resolution. METHODS:
      Fibrosis was induced in BALB/c mice by chronic administration of thioacetamide (8
      weeks). In vivo gene expression analyses, in vitro experiments using hMo isolated
      from the nonparenchymal liver cells fraction, and in vivo experiments with
      depletion of Mo were performed. RESULTS: One day after treatment, hMo from
      fibrotic livers of MSCs-treated animals showed reduced pro-inflammatory and pro
      fibrogenic gene expression profiles. These shifts were more pronounced in AdIGF-I
      MSCs condition. This group showed a significant upregulation in the expression of
      arginase-1 and a higher downregulation of iNOS expression thus suggesting
      decreased levels of oxidative stress. An upregulation in IGF-I and HGF expression
      was observed in hMo from AdIGF-I-MSCs-treated mice suggesting a restorative
      phenotype in these cells. Factors secreted by hMo, preconditioned with MSCs
      supernatant, caused a reduction in the expression levels of hepatic stellate
      cells pro-fibrogenic and activation markers. Interestingly, hMo depletion
      abrogated the therapeutic effect achieved with AdIGF-I-MSCs therapy. Expression
      profile analyses for cell cycle markers were performed on fibrotic livers after
      treatment with AdIGF-I-MSCs and showed a significant regulation in genes related
      to DNA synthesis and repair quality control, cell cycle progression, and DNA
      damage/cellular stress compatible with early induction of pro-regenerative and
      hepatoprotective mechanisms. Moreover, depletion of hMo abrogated such effects on
      the expression of the most highly regulated genes. CONCLUSIONS: Our results
      indicate that AdIGF-I-MSCs are able to induce a pro-fibrotic to resolutive
      phenotype shift on hepatic macrophages, which is a key early event driving liver
      fibrosis amelioration.

PMID- 27876096
TI  - A randomised-controlled trial of the effects of very low-carbohydrate and high
      carbohydrate diets on cognitive performance in patients with type 2 diabetes.
AB  - This study compared the longer-term effects of a very low-carbohydrate, high-fat
      diet with a high-carbohydrate, low-fat diet on cognitive performance in
      individuals with type 2 diabetes (T2D). In total, 115 obese adults with T2D
      (sixty-six males, BMI: 34.6 (sd 4.3) kg/m2, age: 58 (sd 7) years, HbA1c: 7.3 (sd
      1.1) %, diabetes duration: 8 (sd 6) years) were randomised to consume either an
      energy-restricted, very low-carbohydrate, low-saturated-fat (LC) diet or an
      energy-matched high unrefined carbohydrate, low-fat (HC) diet with supervised
      aerobic/resistance exercise (60 min, 3 d/week) for 52 weeks. Body weight, HbA1c
      and cognitive performance assessing perceptual speed, reasoning speed, reasoning
      ability, working memory, verbal fluency, processing speed, short-term memory,
      inhibition and memory scanning speed were assessed before and after intervention.
      No differences in the changes in cognitive test performance scores between the
      diet groups were observed for any of the cognitive function outcomes assessed
      (P>=0.24 time*diet). Percentage reduction in body weight correlated with
      improvements with perceptual speed performance. In obese adults with T2D, both LC
      and HC weight-loss diets combined with exercise training had similar effects on
      cognitive performance. This suggests that an LC diet integrated within a
      lifestyle modification programme can be used as a strategy for weight and
      diabetes management without the concern of negatively affecting cognitive
      function.

PMID- 27876098
TI  - A look back: investigating Google Flu Trends during the influenza A(H1N1)pdm09
      pandemic in Canada, 2009-2010.

PMID- 27876097
TI  - Leishmania donovani development in Phlebotomus argentipes: comparison of
      promastigote- and amastigote-initiated infections.
AB  - Leishmania parasites alternate in their life cycle between promastigote stages
      that develop in the gut of phlebotomine sand flies and amastigotes residing
      inside phagocytic cells of vertebrate hosts. For experimental infections of sand
      flies, promastigotes are frequently used as this way of infection is technically
      easier although ingestion of promastigotes by sand flies is unnatural. Here we
      aimed to answer a critical question, to what extent do promastigote-initiated
      experimental infections differ from those initiated with intracellular
      amastigotes. We performed side-by-side comparison of Leishmania development in
      Phlebotomus argentipes females infected alternatively with promastigotes from log
      phase cultures or amastigotes grown ex vivo in macrophages. Early stage
      infections showed substantial differences in parasite load and representation of
      morphological forms. The differences disappeared along the maturation of
      infections; both groups developed heavy late-stage infections with colonization
      of the stomodeal valve, uniform representation of infective metacyclics and equal
      efficiency of transmission. The results showed that studies focusing on early
      phase of Leishmania development in sand flies should be initiated with
      intracellular amastigotes. However, the use of promastigote stages for sand fly
      infections does not alter significantly the final outcome of Leishmania donovani
      development in P. argentipes and their transmissibility to the vertebrate host.

PMID- 27876100
TI  - Long-term spatio-temporal dynamics of the mosquito Aedes aegypti in temperate
      Argentina.
AB  - Buenos Aires city is located near the southern limit of the distribution of Aedes
      aegypti (Diptera: Culicidae). This study aimed to assess long-term variations in
      the abundance of Ae. aegypti in Buenos Aires in relation to changes in climatic
      conditions. Ae. aegypti weekly oviposition activity was analyzed and compared
      through nine warm seasons from 1998 to 2014, with 200 ovitraps placed across the
      whole extension of the city. The temporal and spatial dynamics of abundances were
      compared among seasons, and their relation with climatic variables were analyzed.
      Results showed a trend to higher peak abundances, a higher number of infested
      sites, and longer duration of the oviposition season through subsequent years,
      consistent with a long-term colonization process. In contrast, thermal
      favorability and rainfall pattern did not show a consistent trend of changes. The
      long-term increase in abundance, and the recently documented expansion of Ae.
      aegypti to colder areas of Buenos Aires province suggest that local populations
      might be adapting to lower temperature conditions. The steadily increasing
      abundances may have implications on the risk of dengue transmission.

PMID- 27876099
TI  - Broad-scale suppression of cotton bollworm, Helicoverpa armigera (Lepidoptera:
      Noctuidae), associated with Bt cotton crops in Northern New South Wales,
      Australia.
AB  - The cotton bollworm, Helicoverpa armigera, is a major pest of many agricultural
      crops in several countries, including Australia. Transgenic cotton, expressing a
      single Bt toxin, was first used in the 1990s to control H. armigera and other
      lepidopteran pests. Landscape scale or greater pest suppression has been reported
      in some countries using this technology. However, a long-term, broad-scale
      pheromone trapping program for H. armigera in a mixed cropping region in eastern
      Australia caught more moths during the deployment of single Bt toxin cotton
      (Ingard(r)) (1996-2004) than in previous years. This response can be attributed,
      at least in part, to (1) a precautionary cap (30% of total cotton grown, by area)
      being applied to Ingard(r) to restrict the development of Bt resistance in the
      pest, and (2) during the Ingard(r) era, cotton production greatly increased (as
      did that of another host plant, sorghum) and H. armigera (in particular the 3rd
      and older generations) responded in concert with this increase in host plant
      availability. However, with the replacement of Ingard(r) with Bollgard II(r)
      cotton (containing two different Bt toxins) in 2005, and recovery of the cotton
      industry from prevailing drought, H. armigera failed to track increased host
      plant supply and moth numbers decreased. Greater toxicity of the two gene
      product, introduction of no cap on Bt cotton proportion, and an increase in
      natural enemy abundance are suggested as the most likely mechanisms responsible
      for the suppression observed.

PMID- 27876101
TI  - Caring for people with dementia in hospital: findings from a survey to identify
      barriers and facilitators to implementing best practice dementia care.
AB  - BACKGROUND: Best practice dementia care is not always provided in the hospital
      setting. Knowledge, attitudes and motivation, practitioner behavior, and external
      factors can influence uptake of best practice and quality care. The aim of this
      study was to determine hospital staff perceived barriers and enablers to
      implementing best practice dementia care. METHODS: A 17-item survey was
      administered at two Australian hospitals between July and September 2014.
      Multidisciplinary staff working in the emergency departments and general medical
      wards were invited to participate in the survey. The survey collected data about
      the respondents' current role, work area, and years of experience, their
      perceived level of confidence and knowledge in dementia care and common symptoms
      of dementia, barriers and enablers to implementing best practice dementia care,
      job satisfaction in caring for people with dementia, and to rate the hospital's
      capacity and available resources to support best practice dementia care. RESULTS:
      A total of 112 survey responses were received. The environment, inadequate
      staffing levels and workload, time, and staff knowledge and skills were
      identified as barriers to implementing best practice dementia care. Most
      respondents rated their knowledge of dementia care and common symptoms of
      dementia, and confidence in recognizing whether a person has dementia, as
      moderate or high dementia. Approximately, half the respondents rated access to
      training and equipment as low or very low. CONCLUSION: The survey findings
      highlighted hospital staff perceived barriers to implementing best practice
      dementia care that can be used to inform locally tailored improvement
      interventions.

PMID- 27876102
TI  - Structural-functional brain changes in depressed patients during and after
      electroconvulsive therapy.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is a non-pharmacological treatment
      that is effective in treating severe and treatment-resistant depression. Although
      the efficacy of ECT has been demonstrated to treat major depressive disorder
      (MDD), the brain mechanisms underlying this process remain unclear. Structural
      functional changes occur with the use of ECT as a treatment for depression based
      on magnetic resonance imaging (MRI). For this reason, we have tried to identify
      the changes that were identified by MRI to try to clarify some operating
      mechanisms of ECT. We focus to brain changes on MRI [structural MRI (sMRI),
      functional MRI (fMRI) and diffusion tensor imging (DTI)] after ECT. METHODS: A
      systematic search of the international literature was performed using the
      bibliographic search engines PubMed and Embase. The research focused on papers
      published up to 30 September 2015. The following Medical Subject Headings (MESH)
      terms were used: electroconvulsive therapy AND (MRI OR fMRI OR DTI). Papers
      published in English were included. Four authors searched the database using a
      predefined strategy to identify potentially eligible studies. RESULTS: There were
      structural changes according to the sMRI performed before and after ECT
      treatment. These changes do not seem to be entirely due to oedema. This
      investigation assessed the functional network connectivity associated with the
      ECT response in MDD. ECT response reverses the relationship from negative to
      positive between the two pairs of networks. CONCLUSION: We found structural
      functional changes in MRI post-ECT. Because of the currently limited MRI data on
      ECT in the literature, it is necessary to conduct further investigations using
      other MRI technology.

PMID- 27876103
TI  - Boston Naming Test (BNT) original, Brazilian adapted version and short forms:
      normative data for illiterate and low-educated older adults.
AB  - BACKGROUND: The aims of this study were (1) to describe and compare the
      performance of illiterate and low-educated older adults, without evidence of
      cognitive impairment, on different versions of the Boston Naming Test (BNT)
      original, Brazilian adapted, abbreviated 30-item (even and odd) and 15-item from
      the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) battery;
      (2) to compare performance on the original versus adapted versions of the BNT.
      METHODS: A total of 180 healthy older adults (60 years or older) were stratified
      according to educational level (0, 1-2, and 3-4 years), and age (60-69, 70-79,
      and >= 80 years). The protocol comprised the following instruments: Mini-Mental
      State Examination (MMSE), Brief Cognitive Screening Battery (BCSB), Functional
      Activities Questionnaire (FAQ), Geriatric Depression Scale (GDS), and the BNT.
      RESULTS: The illiterate participants had poorer performance than the educated
      participants. The performance of the two educated groups was similar on all
      versions of the BNT. A higher number of correct responses were observed on the
      adapted BNT than on the original BNT in all three education groups. CONCLUSIONS:
      The adapted BNT appears to be the most suitable for use in the low-educated
      Brazilian population. The present study provided normative data for low-educated
      elderly on several different versions of the BNT, which may be helpful in
      diagnosing naming deficits among elderly in these strata of the population.

PMID- 27876104
TI  - A cohort study of unstable overdose patients treated with intravenous lipid
      emulsion therapy.
AB  - OBJECTIVES: Intravenous lipid emulsion (ILE) has been used increasingly over the
      last decade for a range of drug overdoses. Although the use of ILE in local
      anesthetic toxicity (LAST) is well established, the hemodynamic effectiveness of
      ILE in non-LAST poisonings is still unclear. Thus, the primary objective of this
      study was to examine a cohort of poisoned patients in whom ILE was administered.
      METHODS: Consecutive patients were identified by calls to a regional poison
      center from May 1, 2012 to May 30, 2014. Patients were enrolled if they ingested
      a drug, developed hemodynamic instability, failed conventional treatment, and
      received ILE therapy. Data were collected by medical record review. The primary
      outcome was the change in mean arterial pressure (MAP) in the first hour after
      ILE administration. Secondary outcomes included survival, length of stay, and the
      effect of drug class on patient outcome. RESULTS: Thirty-six patients were
      enrolled. Agents ingested included calcium channel blockers and beta blockers
      (10/36, 27.8%), tricyclic antidepressants (5/36, 13.9%), bupropion (3/36, 8.3%),
      and antiepileptic agents (1/36, 2.8%). Seventeen patients (47.2%) ingested
      multiple agents. Twenty-five patients survived (69.0%). Overall, MAP increased by
      13.79 mm Hg (95% CI 1.43-26.15); this did not meet our a priori definition of
      clinical significance. CONCLUSIONS: Our study did not find a clinically important
      improvement in MAP after ILE administration. Until future research is done to
      more definitively study its efficacy, ILE should remain a potential treatment
      option for hemodynamically unstable overdose patients only after conventional
      therapy has failed.

PMID- 27876105
TI  - Psychological interventions to reduce suicidality in high-risk patients with
      major depression: a randomized controlled trial.
AB  - BACKGROUND: Positive psychological constructs have been associated with reduced
      suicidal ideation, and interventions to cultivate positive feelings have the
      potential to reduce suicide risk. This study compares the efficacy of a 6-week,
      telephone-based positive psychology (PP) intervention against a cognition-focused
      (CF) control intervention among patients recently hospitalized for depression and
      suicidal ideation or behavior. METHOD: A total of 65 adults with a current major
      depressive episode reporting suicidal ideation or a recent suicide attempt were
      enrolled from participating in-patient psychiatric units. Prior to discharge,
      participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In
      both interventions, participants received a treatment manual, performed weekly PP
      (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and
      completed weekly one-on-one telephone sessions over 6 weeks. Between-group
      differences in hopelessness (primary outcome), depression, suicidality and
      positive psychological constructs at 6 and 12 weeks were tested using mixed
      effects models accounting for intensity of post-hospitalization psychiatric
      treatment. RESULTS: Compared with PP, the CF intervention was associated with
      significantly greater improvements in hopelessness at 6 weeks (beta = -3.15, 95%
      confidence interval -6.18 to -0.12, effect size = -0.84, p = 0.04), but not 12
      weeks. Similarly, the CF intervention led to greater improvements in depression,
      suicidal ideation, optimism and gratitude at 6 and 12 weeks. CONCLUSIONS:
      Contrary to our hypothesis, the CF intervention was superior to PP in improving
      hopelessness, other suicide risk factors and positive psychological constructs
      during a key post-discharge period among suicidal patients with depression.
      Further study of this CF intervention is warranted in populations at high suicide
      risk.

PMID- 27876107
TI  - Sodium butyrate protects mice from the development of the early signs of non
      alcoholic fatty liver disease: role of melatonin and lipid peroxidation.
AB  - Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver
      diseases worldwide with universally accepted treatments still lacking. Oral
      supplementation of sodium butyrate (SoB) has been suggested to attenuate liver
      damage of various aetiologies. Our study aimed to further delineate mechanisms
      involved in the SoB-dependent hepatic protection using a mouse model of fructose
      induced NAFLD and in in vitro models. C57BL/6J mice were either pair-fed a
      fructose-enriched liquid diet +/-0.6 g/kg body weight per d SoB or standard chow
      for 6 weeks. Markers of liver damage, intestinal barrier function, glucose
      metabolism, toll-like receptor-4 (TLR-4) and melatonin signalling were determined
      in mice. Differentiated human carcinoma colon-2 (Caco-2) and J774A.1 cells were
      used to determine molecular mechanisms involved in the effects of SoB. Despite
      having no effects on markers of intestinal barrier function and glucose
      metabolism or body weight gain, SoB supplementation significantly attenuated
      fructose-induced hepatic TAG accumulation and inflammation. The protective
      effects of SoB were associated with significantly lower expression of markers of
      the TLR-4-dependent signalling cascade, concentrations of inducible nitric oxide
      synthase (iNOS) protein and 4-hydroxynonenal protein adducts in liver. Treatment
      with SoB increased melatonin levels and expression of enzymes involved in
      melatonin synthesis in duodenal tissue and Caco-2 cells. Moreover, treatment with
      melatonin significantly attenuated lipopolysaccharide-induced expression of iNOS
      and nitrate levels in J774A.1 cells. Taken together, our results indicated that
      the protective effects of SoB on the development of fructose-induced NAFLD in
      mice are associated with an increased duodenal melatonin synthesis and
      attenuation of iNOS induction in liver.

PMID- 27876106
TI  - Hubris and Humility Effect and the Domain-Masculine Intelligence Type in Two
      Countries: Colombia and the UK.
AB  - Spanish-speaking Colombian (n = 50) and English-speaking British (N = 52) adults
      completed a self-assessed intelligence measure that yielded a score on domain
      masculine intelligence (DMIQ), a composite of mathematical/logical and spatial
      intelligences. They also completed a Sex Role inventory in order to establish
      their masculinity and femininity. Males in both countries gave significantly
      higher self-estimates (Colombia: Males 110.36, Females 100.75, d = .94; England:
      Males 114.37, Females 105.75, d = .86; both p < .01) than females but sex role
      was note related to DMIQ. However there was a positive relationship between
      masculinity and DMIQ (r = .45, r = .39, p < .01), but only for males. Cultural
      issues in self-assessed intelligence and limitations, particularly sample size of
      this exploratory study are considered.

PMID- 27876108
TI  - Unmarried patients with early cognitive impairment are more likely than their
      married counterparts to complete advance care plans.
AB  - BACKGROUND: Patients with early cognitive impairment (ECI) face the prospect of
      progressive cognitive decline that impairs their ability to make decisions on
      financial and personal matters. Advance care planning (ACP) is a process that
      facilitates decision making on future care and often includes identifying a proxy
      decision maker. This prospective study explores factors related to completion or
      non-completion of ACP in patients with ECI. METHODS: Patients with ECI (n = 158,
      M age = 76.2 +/- 7.25 years) at a memory clinic received psycho-education and
      counseling on the importance of ACP and followed-up longitudinally for up to 12
      months to ascertain if ACP had been completed. Univariate and logistic regression
      were used to analyze factors related to completion and non-completion of ACP.
      RESULTS: Seventy-seven patients (48.7%) were initially willing to consider ACP
      after the counseling and psycho-educational session but only 17 (11.0%)
      eventually completed ACP. On logistic regression, patients who were single were
      8.9 times more likely to complete ACP than those who were married (p = 0.007).
      Among those initially willing to consider ACP, factors impeding completion of ACP
      included patient (48.0%), process (31.0%), and family factors (21.0%).
      CONCLUSIONS: As unmarried patients may not have immediate family members to
      depend on to make decisions, they may perceive ACP to be more important and
      relevant. Understanding the barriers to ACP completion can facilitate targeted
      interventions to improve the uptake of ACP.

PMID- 27876109
TI  - The complex metabolism of trimethylamine in humans: endogenous and exogenous
      sources-CORRIGENDUM.

PMID- 27876110
TI  - Determinants of microstructural, dimensional and bone mineral changes postpartum
      in Swedish women.
AB  - During lactation, areal (a) and volumetric (v) bone mineral density (BMD) are
      known to temporarily decrease. Factors that affect skeletal changes postpartum
      are not fully elucidated. The aim was to study determinants of the previously
      observed changes in aBMD at lumbar spine, and cortical vBMD, microstructure and
      dimensions at ultra-distal tibia postpartum. Women (25-40 years) were studied
      longitudinally at 2 weeks (baseline) and 4 months (n 81), 12 months (n 79) and 18
      months (n 58) postpartum. At each visit, blood samples were collected, body
      weight and height were measured and information about lactation habits, oestrogen
      contraceptives and physical activity was obtained. Ca intake was measured using 4
      d food diaries at 4 months postpartum. Serum 25-hydroxyvitamin D (25OHD) was
      analysed by liquid chromatography-tandem MS. Skeletal changes were assessed with
      dual-energy X-ray absorptiometry and high-resolution peripheral quantitative
      computed tomography. Mean baseline BMI was 24.8 (sd 3.1) kg/m2. Median (quartiles
      1-3) duration of total lactation was 8.1 (6.8-10.4) months. Longer duration of
      full lactation was associated with larger decreases of lumbar spine aBMD and
      tibia vBMD and microstructure. Higher baseline body weight was associated with
      smaller decreases in tibia vBMD and microstructure. Higher Ca intake was
      associated with smaller decreases in tibia cortical vBMD and thickness. Higher
      baseline 25OHD was only associated with larger decreases in lumbar spine aBMD. In
      conclusion, lactation and body weight were the main determinants of skeletal
      changes during the first 18 months postpartum. Ca intake and serum concentrations
      of 25OHD appear to have different associations with cortical and trabecular bone.

PMID- 27876111
TI  - The remarkable Dr Robertson.
AB  - Muriel Robertson (1883-1973) was a pioneering protozoologist who made a
      staggering number of important contributions to the fields of parasitology,
      bacteriology and immunology during her career, which spanned nearly 60 years.
      These contributions were all the more remarkable given the scientific and social
      times in which she worked. While Muriel is perhaps best known for her work on the
      life cycle and transmission of the African trypanosome, Trypanosoma brucei, which
      she carried out in Uganda at the height of a major Sleeping Sickness epidemic,
      her work on the Clostridia during the First and Second World Wars made
      significant contributions to the understanding of anaerobes and to the
      development of anti-toxoid vaccines, and her work on the immunology of
      Trichomonas foetus infections in cattle, carried out in collaboration with the
      veterinarian W. R. Kerr, resulted in changes in farming practices that very
      quickly eradicated trichomoniasis from cattle herds in Northern Ireland. The
      significance of her work was recognized with the award of Fellow of the Royal
      Society in 1947 and an Honorary Doctorate of Law from the University of Glasgow,
      where she had earlier studied, in 1948.

PMID- 27876113
TI  - Rosmarinic acid reverses the effects of metronidazole-induced infertility in male
      albino rats.
AB  - Rosmarinic acid (RA) is a natural antioxidant that has many biological
      activities. In the present study we investigated the potential of RA to reverse
      the negative effects of the widely used antibiotic and antiprotozoal agent
      metronidazole (MTZ), which is known to induce reversible male infertility. Two
      doses of RA (5 and 15mg kg-1) were studied in sexually mature rats with and
      without MTZ-induced infertility. Rats were intraperitoneally injected with 5mg kg
      1 RA or 15mg kg-1 RA (in distilled water) and, 45min later, they were
      intraperitoneally injected with 40mg kg-1 MTZ (in distilled water). Cauda
      epididymidal sperm suspensions were used to assess sperm count, motility and
      morphology. Histological and ultrastructural studies were performed on the testes
      and cauda epididymidis. In rats in which infertility was not induced, neither
      dose of RA affected the parameters assessed. However, in sexually mature rats in
      which infertility was induced by 40mg kg-1 MTZ, RA at both 5 and 15mg kg-1
      ameliorated the damaging effects of MTZ on final bodyweight (30 days later),
      sperm motility and morphology. Only 5mg kg-1 RA, and not 15mg kg-1 RA, improved
      the harmful effects of MTZ on the sperm count and testis ultrastructure. The
      findings of the present study have considerable clinical implications and suggest
      a possible use for RA to reverse the negative effects of MTZ on male fertility,
      the male reproductive system and spermatogenesis.

PMID- 27876112
TI  - Antioxidant defense of Nrf2 vs pro-inflammatory system of NF-kappaB during the
      amoebic liver infection in hamster.
AB  - Entamoeba histolytica is the causative agent of amoebic liver abscess (ALA),
      which course with an uncontrolled inflammation and nitro-oxidative stresses,
      although it is well known that amoeba has an effective defence mechanisms against
      this toxic environment, the underlying molecular factors responsible for
      progression of tissue damage remain largely unknown. The purpose of the present
      study was to determine during the acute stage of ALA in hamsters, the involvement
      of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor-kappa B
      (NF-kappaB), which are activated in response to oxidative stress. From 12 h post
      infection the ALA was visible, haematoxylin-eosin and Masson's trichrome stains
      were consistent with these observations, and alanine aminotransferase, alkaline
      phosphatase and gamma-glutamyl transpeptidase serum activities were increased
      too. At 48 h after infection, liver glycogen content was significantly reduced.
      Western blot analyses showed that 4-Hydroxy-2-nonenal peaked at 12 h, while
      glycogen synthase kinase-3beta, cleaved caspase-3, pNF-kappaB, interleukin-1beta
      and tumour necrosis factor-alpha were overexpressed from 12 to 48 h post
      infection. Otherwise, Nrf2 and superoxide dismutase-1, decreased at 48 h and
      catalase declined at 36 and 48 h. Furthermore, heme oxygenase-1 was increased at
      12 and 24 h and decreased to normal levels at 36 and 48 h. These findings suggest
      for the first time that the host antioxidant system of Nrf2 is influenced during
      ALA.

PMID- 27876114
TI  - Modified platelet-rich plasma with transforming growth factor beta1
      neutralization antibody injection may reduce recurrence rate of urethral
      stricture.
AB  - Urethral stricture is one of the most bothersome urologic disease among
      urologists and has a substantial impact on quality of life and healthcare costs.
      Although it can be cured with internal urethrotomy easily, post-surgery stricture
      recurrence is challenging. Several adjuvant therapies have been used in
      conjunction with internal urethrotomy but none of them are used routinely because
      the pathophysiology of the disease is still obscure. Fibrosis is the most accused
      hypothesis for the action. Platelet-rich plasma (PRP) is an autologous blood
      product containing a high concentration of platelets that is being used for a
      very wide range of clinical healing applications. It comprises a concentration of
      fundamental protein growth factors shown to be actively excreted by platelets to
      initiate accurate wound healing. Although PRP can play a critical role in wound
      healing and has been used in fibrotic diseases successfully, it has some
      deleterious cytokines such as transforming growth factor beta1 (TGF beta1) which
      can also cause fibrosis. The new hypothesis is that the subcutaneous injection of
      neutralized platelet-rich plasma with TGFbeta1 antibody at the planned
      urethrotomy site may prevent recurrence and provide superior healing and long
      term results.

PMID- 27876115
TI  - The "first digit law" - A hypothesis on its possible impact on medicine and
      development aid.
AB  - The "first digit law" or "Benford's law" is a mathematical distribution
      discovered by Simon Newcomb and Frank Benford. It states, that the probability of
      the leading number d (d?{1,...,9}) in many natural datasets follows: P (d)=log10
      (d+1)-log10 (d)=log10 (1+1/d). It was successfully used through tax authorities
      and "forensic accounting" in order to detect fraud and other irregularities.
      Benfords law was almost neglected for its use outside financial accounting. The
      planning for health care systems in developing countries is extremely dependant
      on good, valid data. Whether you plan the catchment area for the future district
      hospitals, the number of health posts, the staff establishment for the central
      hospital or the drug budget in the Ministry. The "first digit law" can be used in
      medicine, public health, physiology and development aid to unmask questionable
      data, to discover unexpected challenges, difficulties in the data collection
      process, loss through corruption and criminal fraud. Our hypothesis suggests,
      that the "first digit law" is a cost effective tool, which is easy to use for
      most people in the medical profession, which does not really needs complicated
      statistical software and can be used on the spot, even in the resource restricted
      conditions of developing countries. Several preconditions (like the size of the
      data set and its reach over more than two dimensions) have to be fulfilled, but
      then Benfords law can be used by any clinician, physiologist, public health
      specialist or aid consultant without difficulties and without deeper statistical
      knowledge in the four steps, we suggest in this article. The consequences will be
      different depending on the level (local regional, national, continental,
      international) on which you will use the law. All levels will be enabled to get
      insight into the validity of the data-challenges for the other levels without the
      help of trained statisticians or accountants. We believe that the "first digit
      law" is a vastly underestimated and neglected, but extremely useful tool for the
      identification of unexpected challenges, supervision and control in various parts
      of medicine and public health for almost all aspects of development aid.

PMID- 27876116
TI  - Could field cancerization be interpreted as a biochemical anomaly amplification
      due to transformed cells?
AB  - Field cancerization is a concept used to explain cellular and molecular
      alterations in tissue associated to neoplasia and cancer. This effect was
      proposed by Slaughter in order to explain the development of multiple primary
      tumors and locally recurrent cancer. The particular changes associated with this
      effect, in each type of cancer, have been detected even at distances greater than
      10cm off the tumor, in areas classified as normal by histopathological studies.
      Early detection of lung, colon, and ovary cancer has been reported by the use of
      Partial Wave Microscopy Spectroscopy (PWS) and has been explained in terms of the
      field cancerization effect. Until now, field cancerization has been studied as a
      field effect and we hypothesize that it can be understood as an amplifying effect
      of biochemical abnormalities in cells, which leads us to ask the question: Could
      field cancerization be interpreted as a biochemical anomaly amplification due to
      transformed cells? We propose this question because the biochemical changes due
      to field cancerization alter the dynamics of molecules and cells in abnormal
      tissues in comparison to normal ones, these alterations modify the interaction of
      intracellular and extracellular medium, as well as cellular movement. We
      hypothesize that field cancerization when interpreted as an amplification effect
      can be used for the early detection of cancer by measuring the change of cell
      dynamics.

PMID- 27876118
TI  - Flat shoes increase neurogenesis.
AB  - The impairment of the horizontal is caused by elevation of the heel of the foot
      from the ground. Receptors in the soles of the feet provide a mapping of body
      orientation to the upright, and is identical to Mittelstaedt's idiotropic
      tendency. Initiation of gait wearing flat shoes without elevation of the heel is
      sufficient to change to a truthful horizontal. Using flat shoes increases
      neurogenesis and leads to a decreased frequency of diseases of the nervous
      system.

PMID- 27876117
TI  - Neonatal abstinence syndrome and the gastrointestinal tract.
AB  - Development of a healthy gut microbiome is essential in newborns to establish
      immunity and protection from pathogens. Recent studies suggest that infants who
      develop dysbiosis may be at risk for lifelong adverse health consequences.
      Exposure to opioid drugs during pregnancy is a factor of potential importance for
      microbiome health that has not yet been investigated. Since these infants are
      born after an entire gestation exposed to mu opioid receptor agonists and have
      severe gastrointestinal and neurological symptoms, we hypothesize that these
      infants are at risk for dysbiosis. We speculate that opioid exposure during
      gestation and development of NAS at birth may lead to a dysbiotic gut microbiome,
      which may impair normal microbiome succession and development, and impact future
      health of these children.

PMID- 27876119
TI  - Primary bladder neck obstruction may be determined by postural imbalances.
AB  - Primary bladder neck obstruction (PBNO) is a frequent under-investigated
      urological condition in which the bladder neck fails to open adequately during
      voiding. In the majority of cases no known etiological factor can be found. In
      this study we propose a new hypothesis to explain the origin of the disease in
      young male patients with no neurological disorders. We suggest a possible role of
      an unbalanced biomechanics of the pelvis on urethral sphincters activity and on
      functional bladder capacity. To support the proposed hypothesis, we present pilot
      gait analysis data of young male patients with primary bladder neck obstruction.

PMID- 27876120
TI  - Migraine: A disorder of metabolism?
AB  - The treatment and prevention of migraine within the last decade has become
      largely pharmacological. While there is little doubt that the advent of drugs
      (e.g. triptans) has helped many migraine sufferers to lead a normal life, there
      is still little knowledge with respect to the factors responsible for
      precipitating a migraine attack. Evidence from biochemical and behavioural
      studies from a number of disciplines is integrated to put forward the proposal
      that migraine is part of a cascade of events, which together act to protect the
      organism when confronted by a metabolic challenge.

PMID- 27876121
TI  - Possible neuronal mechanisms of sleep disturbances in patients with autism
      spectrum disorders and attention-deficit/hyperactivity disorder.
AB  - The most common form of sleep disturbance among both patients with autism
      spectrum disorders and patients with attention-deficit/hyperactivity disorder is
      sleep-onset insomnia, but the neuronal mechanisms underlying it have yet to be
      elucidated and no specific treatment strategy has been proposed. This means that
      many caregivers struggle to manage this problem on a daily basis. This paper
      presents a hypothesis about the neuronal mechanisms underlying insomnia in
      patients with autism spectrum disorders and attention-deficit/hyperactivity
      disorder based on recent clinical and basic research. It is proposed that three
      neuronal mechanisms (increased orexinergic system activity, reduced 5
      hydroxytryptamine and melatonergic system activity, rapid eye movement sleep
      reduction) are involved in insomnia in both autism spectrum disorders and
      attention-deficit/hyperactivity disorder. This suggests that antagonists against
      the orexin receptors may have beneficial effects on insomnia in patients with
      autism spectrum disorders or attention-deficit/hyperactivity disorder. To the
      best of the author's knowledge there has been no research into the effects of
      this agent on insomnia in these patient groups. Large, controlled trials should
      be carried out.

PMID- 27876122
TI  - A hypothesis on the mechanism of action of high-dose thyroid in refractory mood
      disorders.
AB  - Multiple lines of evidence suggest the hypothesis that high dose thyroid therapy
      corrects for cellular hypothyroidism found in bipolar disorders. Evidence
      indicates that bipolar disorders are associated with mitochondrial dysfunction
      which results in low cellular adenosine 5'-triphosphate (ATP) levels. Transport
      of thyroid hormones into cells is energy intensive and dependent on ATP except in
      the pituitary gland. Inadequate ATP levels makes it difficult to get thyroid
      hormone into cells leading to cellular hypothyroidism. This creates a condition
      where the blood and pituitary levels of thyroid hormone are normal but low in
      other tissues. High dose thyroid therapy produces a gradient that is sufficient
      for thyroid hormone to diffuse into cells correcting cellular hypothyroidism. If
      this hypothesis is correct there are number of implications. The two most
      important are: On average patients suffering from a bipolar disorder die 10
      20years earlier than the general population. The medical sequelae associated with
      bipolar disorders cause far more deaths than suicide. If high dose thyroid
      corrects for cellular hypothyroidism it could well decrease the medical morbidity
      and mortality associated with bipolar disorders that are the result of cellular
      hypothyroidism. Thus high dose thyroid would be a first treatment that decreases
      the considerable medical morbidity and mortality associated with the bipolar
      disorders. This would stand in stark contrast to most psychiatric medications
      that can that increase morbidity and mortality. It would also reinforce the
      safety of HDT. The second implication is thyroid hormone blood levels in patients
      suffering from a bipolar disorder do not accurately reflect the true thyroid
      status.

PMID- 27876123
TI  - BLM germline and somatic PKMYT1 and AHCY mutations: Genetic variations beyond
      MYCN and prognosis in neuroblastoma.
AB  - Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood and
      often lethal in childhood. Clinical and biologic characteristics that are
      independently prognostic of outcome in NB are currently used for risk
      stratification to optimally the therapy. It includes age at diagnosis,
      International Neuroblastoma Staging System tumor histopathology and MYCN
      amplification. However, even in patients with theoretically good prognosis, such
      as localized tumor and non-amplified MYCN, either disease progress or recurrence
      may occur. Potential genetic determinants of this unfavorable behavior are not
      yet fully clarified. The presence of elevated expression of AHCY, PKMYT1, and BLM
      has accompanied poor prognosis MYCN-amplified neuroblastoma patients. Considering
      the potential implication of these genes on the clinical management of NB, we
      hypothesize that the identification of genetic variations may have significant
      impact during development of the recurrent or progressive disease. Using targeted
      DNA sequencing, we analyzed the mutation profiles of the genes PKMYT1, AHCY, and
      BLM in tumor samples of five patients with MYCN amplified and 15 MYCN non
      amplified NB. In our study, BLM germline variants were detected in two patients
      with MYCN-non-amplified neuroblastoma. Our data allow us to hypothesize that,
      regardless of MYCN status, these mutations partially abolish BLM protein activity
      by impairing its ATPase and helicase activities. BLM mutations are also
      clinically relevant because BLM plays an important role in DNA damage repair and
      the maintenance of genomic integrity. We also found a novel variant in our
      cohort, PKMYT1 mutation localized in the C-terminal domain with effect unknown on
      NB. We hypothesize that this variant may affect the catalytic activity of PKMYT1
      in NB, specifically when CDK1 is complexed to cyclins. The prognostic value of
      this mutation must be further investigated. Another mutation identified was a
      nonsynonymous variant in AHCY. This variant may be related to the slow
      progression of the disease, even in more aggressive cases. It affects the
      maintenance of the catalytic capacity of AHCY, leading to the consequent
      functional effects observed in the NB patients studied. In conclusion, our
      hypothesis may provide that mutations in BLM, AHCY and PKMYT1 genes found in
      children with MYCN-amplified or MYCN-non amplified neuroblastomas, may be
      associated with the prognosis of the disease.

PMID- 27876124
TI  - Estimating the influence of aortic-stent grafts after endovascular aneurysm
      repair: Are we missing something?
AB  - The implantation of a stiff aortic endograft for endovascular abdominal aneurysm
      repair (EVAR) has been reported to increase aortic stiffness and pulse wave
      velocity (PWV), raising potential concern over deterioration of myocardial
      performance. Yet, additional stiffness indices such as the augmentation index
      (AIx), reflection magnitude (RM) and changes in augmentation pressure (AP) have
      not been studied adequately to facilitate and improve our knowledge regarding the
      ways that EVAR affects central hemodynamics. In this article it is suggested that
      the implantation of an aortic stent-graft exerts its immediate effects not only
      by interposing extra stiffness on the infrarenal segment but by also modifying
      the pulse wave reflection site and changing the aortic flow field without
      necessarily causing significant alterations in PWV. Hence, further studies on
      myocardial performance in large patient populations are expected to delineate the
      precise influence of different designs of EVAR endografts on the cardiovascular
      hemodynamic which, in turn, can affect the morbidity and survival of these
      patients.

PMID- 27876125
TI  - Is there a relationship between sinusitis and psychological disorders?
AB  - Chronic rhinosinusitis refers to inflammation of the nasal and sinuses mucosa and
      the main criteria for diagnosis of this disease related to the nasal cavity or
      the facial area. According to several reports based on the relationship of this
      disease with mental disorders, psychological issues are missing in the criteria
      of chronic rhinosinusitis diagnosis. In this study the etiology and clinical
      symptoms of the disease were studied by searching scientific databases and
      authentic Iranian Medicine books such as Avicenna's book The Canon of Medicine
      (Al-Qanun fi't-Tibb) that now taught in medicine schools of the Traditional East
      Asian; the results of this study showed that rhinosinusitis accompaniment with
      psychological symptoms are listed in abundance not only in old books but also in
      scientific literature before 1928 but after the discovery of antibiotics and
      extreme attention in the context of physiopathological assignment of diseases to
      pathogens, this relationship has been weakened. Given the positive results of
      recent studies on rhinosinusitis accompaniment with psychological disorders it is
      suggested that more studies are needed to explore the relationship between
      chronic rhinosinusitis and psychological diseases and, if necessary, to be
      included in the diagnostic criteria as a diagnostic standard.

PMID- 27876126
TI  - Regular sun exposure benefits health.
AB  - Since it was discovered that UV radiation was the main environmental cause of
      skin cancer, primary prevention programs have been started. These programs advise
      to avoid exposure to sunlight. However, the question arises whether sun-shunning
      behaviour might have an effect on general health. During the last decades new
      favourable associations between sunlight and disease have been discovered. There
      is growing observational and experimental evidence that regular exposure to
      sunlight contributes to the prevention of colon-, breast-, prostate cancer, non
      Hodgkin lymphoma, multiple sclerosis, hypertension and diabetes. Initially, these
      beneficial effects were ascribed to vitamin D. Recently it became evident that
      immunomodulation, the formation of nitric oxide, melatonin, serotonin, and the
      effect of (sun)light on circadian clocks, are involved as well. In Europe (above
      50 degrees north latitude), the risk of skin cancer (particularly melanoma) is
      mainly caused by an intermittent pattern of exposure, while regular exposure
      confers a relatively low risk. The available data on the negative and positive
      effects of sun exposure are discussed. Considering these data we hypothesize that
      regular sun exposure benefits health.

PMID- 27876128
TI  - Can subphysiological cold application be utilized in excessive dermal scarring
      prophylaxis and treatment?: A promising hypothetical perspective.
AB  - Excessive dermal scarring (EDS) is a wound healing complication, characterized by
      protruded erythematous and inelastic 'proliferative scar tissue' which is
      associated with increased and prolonged inflammation process within the wound
      microenvironment. As inflammation plays a key role in this process, methods to
      contain or attenuate excessive inflammation hold promise in treatment and
      prophylaxis of EDS conditions. While cold exposure is notorious as the causative
      agent a wide array of morbidities and fatalities, its tempered use is exploited
      in medicine for ablative and therapeutic applications. "Subphysiological cold"
      has been administered for its antiinflammatory effects which act via decreasing
      vascular permeability and downregulating proliferation of cells in the wound
      environment; this knowledge supports our hypothesis that "subphysiological cold
      application" can also be utilized in human EDS prophylaxis and treatment. In this
      study, we are reviewing the mechanisms of its both deleterious and therapeutic
      actions and suggesting another possible application for prevention and/or
      treatment of human EDS conditions.

PMID- 27876127
TI  - In silico prediction of specific pathways that regulate mesangial cell
      proliferation in IgA nephropathy.
AB  - IgA nephropathy is one of the most common forms of primary glomerulonephritis
      worldwide leading to end-stage renal disease. Proliferation of mesangial cells,
      i.e., the multifunctional cells located in the intracapillary region of
      glomeruli, after IgA- dominant immune deposition is the major histologic feature
      in IgA nephropathy. In spite of several studies on molecular basis of
      proliferation in these cells, specific pathways responsible for regulation of
      proliferation are still to be discovered. In this study, we predicted a specific
      signaling pathway started from transferrin receptor (TFRC), a specific IgA1
      receptor on mesangial cells, toward a set of proliferation-related proteins. The
      final constructed subnetwork was presented after filtration and evaluation. The
      results suggest that estrogen receptor (ESR1) as a hub protein in the significant
      subnetwork has an important role in the mesangial cell proliferation and is a
      potential target for IgA nephropathy therapy. In conclusion, this study suggests
      a novel hypothesis for the mechanism of pathogenesis in IgA nephropathy and is a
      reasonable start point for the future experimental studies on mesangial
      proliferation process in this disease.

PMID- 27876129
TI  - Metabolic syndrome - A truly psychosomatic disorder? A global hypothesis.
AB  - Exact cause of the metabolic syndrome [MS], a global epidemic, is still unclear.
      Man has same fundamental needs to live as animals but modern man's life-style
      compels him to acquire certainty of resources for all his needs in a complex
      social network. Today money has become the sole life essential need. Contrarily
      none of the animals needs to earn money. Brain is also an organ of the human body
      with a unique thought process to define logical actions to achieve a person's
      goals. This way life is a flow of desires followed by logical actions. The person
      struggles to attain desired goals via the allostatic load but a perceived
      insurmountable threat can make his flow of life stalled to freeze him. Published
      data from varied branches of medical science indicates role of hormones in
      overall homeostasis. Particularly multifaceted role of serotonin is well
      documented. Adrenalin being the primary mediator of Cori cycle is also well
      known. From the integration of observations from published data with reference to
      common human's modern lifestyle, it is hypothesized that a perceived trapped
      situation in life creates acute chaos of thoughts in brain, which results in
      acute excess of stress hormones and concurrent depletion of resting hormones,
      which in turn triggers MS. In global terms, MS indicates an acute imbalance of a
      few hormones and implies psychosomatic roots of the disorder. This may pave a
      better way in deciding a personalized holistic protocol with combination of
      counter regulatory psychoactive medications.

PMID- 27876130
TI  - The potential behavioral and economic impacts of widespread HMG-CoA reductase
      inhibitor (statin) use.
AB  - Dyslipidemia is a common pathology throughout the industrialized world, and HMG
      CoA reductase inhibitors (statins) are often administered to treat elevated lipid
      levels. Substantial concern has been raised regarding the aggressive clinical
      lowering of cholesterol, particularly in light of a growing body of research
      linking low circulating lipid levels with negative behavioral outcomes in both
      human samples and non-human primate models. In 2009, Goldstein and colleagues
      tentatively speculated that the greed, impulsiveness, and lack of foresight that
      lead to the worldwide economic collapse in 2007-2008 could have been caused (in
      part) by depressed population cholesterol levels resulting from the widespread
      use of statins by workers in the financial services industry. This paper reviews
      the literature that links low circulating lipid levels with neurobehavioral
      dysfunction, develops Goldstein and colleagues' initial speculation into a formal
      hypothesis, and proposes several specific studies that could rigorously
      empirically evaluate this hypothesis.

PMID- 27876131
TI  - Chemosensitization role of fulvestrant in combination with chemotherapy in
      postmenopausal hormone receptor positive and human epidermal growth factor
      negative metastatic breast cancer.
AB  - In metastatic breast cancer (MBC), hormone receptor positive (HR+), human
      epidermal growth factor negative (HER2-) subtype accounts for the majority. With
      various new modalities available to prolong life span in this group of patients,
      the effect is distant from optimum. Prevalent strategy of treating postmenopausal
      HR+ HER2- MBC is application of chemotherapy (CT) after progression of disease on
      endocrine therapy (ET) of several lines. Generally, ET targets HR+ ingredients
      and CT works better with HR- tumor cells. HR+ MBC, though hormone-sensitive, has
      HR- portion which reacts poorly to ET. Thus, sequential use of ET and CT neglects
      its insensitive part and gives rise to drug resistance, while alleviation of
      tumor burden is the top priority in metastatic setting. Chemohormonal therapy
      (i.e. concomitant use of ET and chemotherapy) complements for the shortcoming of
      current therapy strategy targeting both HR+ and HR- ingredients theoretically.
      Fulvestrant, a pure estrogen receptor antagonist and down-regulator, could be a
      promising agent using concurrently with CT based on chemosensitizing character
      shown in preclinical and pilot clinical studies. It is hypothesized in this
      article that chemohormonal therapy with concurrent fulvestrant and CT would be a
      promising strategy in postmenopausal HR+ HER2- MBC patients. Proof of this
      hypothesis would help control evolvement of tumor burden and acquirement of drug
      resistance over a short period of time.

PMID- 27876132
TI  - Possible role of intronic polymorphisms in the PHACTR1 gene on the development of
      cardiovascular disease.
AB  - Cardiovascular disease (CVD) is a complex multifactorial and polygenetic disease
      in which the interaction of numerous genes, genetic variants, and environmental
      factors plays a major role in its development. In an attempt to demonstrate the
      association between certain genetic variants and CVD, researchers have run large
      genomic wild association studies (GWAS) in recent decades. These studies have
      correlated several genomic variants with the presence of CVD. Recently, certain
      polymorphisms in the phosphatase and actin regulator 1 (PHACTR1) gene have been
      shown to be associated with CVD (i.e., coronary artery disease, coronary artery
      calcification, early onset myocardial infarction, cervical artery dissection and
      hypertension) in different ethnic groups. It is important to state that all of
      the described PHACTR1 genetic variants associated with CVD are located in non
      translating gene regions known as introns. Thus, the purpose of this article is
      to hypothesize the effect of certain intronic polymorphisms in the PHACTR1 gene
      on pathological processes in the cardiovascular system. In addition, we present
      compelling evidence that supports this hypothesis as well as a methodology that
      could be used to assess the allelic effect using in vitro and in vivo models,
      which will ultimately demonstrate the pathophysiological contribution of PHACTR1
      intronic polymorphisms to the development of CVD.

PMID- 27876133
TI  - Skin phenotypes can offer some insight about the association between telomere
      length and cancer susceptibility.
AB  - The role of telomere biology in cancer has been studied for a wide variety of
      different cancers but the association with telomere length has been
      controversial. This is because some cancers have been found to be associated with
      longer telomeres in circulating white cells whilst other cancer types are more
      common in individuals with shorter telomeres. Hence, there has been some
      skepticism as to whether telomere length may be helpful in estimating cancer
      risk. For melanoma, however, results have been fairly consistent showing that
      longer telomeres are associated with an increased risk. This link was first
      discovered because of a link between longer telomeres and a high number of naevi.
      In contrast, for cutaneous squamous cell carcinomas, the relationship is reversed
      with higher risk in individuals with shorter telomeres. Differences in skin
      phenotypes with the presence of high number of naevi versus photoageing with
      solar elastosis and solar keratoses have already been valuable for dermatologists
      as the former phenotype is associated with melanoma whilst the latter is more
      common in patients with squamous cell carcinoma of the skin. The hypothesis is
      that the differences in cutaneous phenotypes already observed by dermatologists
      for skin cancers may, in fact, be useful as well for cancer prediction in general
      as it may reflect underlying telomere biology. This manuscript will address the
      evidence for links between telomere biology, skin phenotypes and cancer risk.

PMID- 27876134
TI  - Geniuses of medical science: Friendly, open and responsible, not mad.
AB  - Recent studies based on biography analysis provide support for the notion that
      the prevalence of mental illness in the creative geniuses of art, literature and
      science is higher than it is in more ordinary folk. However, this relationship
      between madness and genius, which was also addressed by the classical
      philosophers, has been generalized to all branches of professional endeavour.
      Whilst it may hold true for illustrious personalities of the fine arts, we found
      that the relationship proves inappropriate to the biographies of ten individuals
      renowned in history for their innovative contributions to medical science.
      Furthermore, examination of these ten biographies invites the hypothesis that
      certain personality traits - especially, agreeableness, conscientiousness and
      openness to new experience - can act to enhance creativity and protect against
      mental illness.

PMID- 27876135
TI  - From molecules to behavior: An integrative theory of autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders
      for which various theories have been proposed. Each theory brings valuable
      insights and has experimental evidence backing it, yet none provides an
      overarching explanation for each of the pathological aspects involved in ASD.
      Here we present an integrative theory of ASD, centered on a sequence of events
      spanning from the molecular to the behavioral level. We propose that an
      abnormality in the interplay between retinoic acid and sex hormones predisposes
      an individual to specific molecular malfunctions. In turn, this molecular
      syndrome generates an altered brain connectivity between the cerebellum, the
      midbrain dopaminergic areas, and the prefrontal cortex. Lastly, this
      disconnection would generate specific behavioral traits traditionally involved in
      ASD. Therefore, this paper represents a step forward in unifying different levels
      of pathological features into novel integrated testable hypotheses.

PMID- 27876136
TI  - Worse or better?-Cirrhosis with hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) accounts for about 90% of all malignant tumors of
      liver, ranking fifth in the worldwide incidence of malignant tumors and the third
      in fatality. More and more evidences suggest that cancer is a metabolic-related
      disease. From the analysis of recent clinical research data, we found that as the
      severity of the cirrhosis aggravated, patients with HCC and end-stage liver
      cirrhosis had a flat energy metabolism which was better than it in patients with
      simple end-stage liver cirrhosis. Based on these clinical phenomenon, the major
      aim of this study is to present a new hypothesis: "compensated liver function
      mechanism" for patients with HCC and liver cirrhosis, cancer cells may play a
      role to compensate liver function. In this study, we elaborated relevant content
      about this novel standpoint combined with tumor energy metabolism reprogramming
      mechanism and tumor cell origin as well as cell exchange mechanism.

PMID- 27876137
TI  - Cathepsin K: The association between Cathepsin K expression and sphenoid sinus
      invasion of pituitary adenomas.
AB  - Pituitary adenomas with sphenoid sinus or clivus invasion are not uncommon, but
      the pathogenesis responsible for this phenomenon remains unclear. Cathepsin K,
      expressed predominantly in osteoclasts, can degrade type I collagen and plays an
      essential role in bone resorption. Recent studies reported the expression of
      Cathepsin K in various malignant tumors, such as bone, breast, lung and prostate
      cancers, and its expression is further increased in bone metastasis or invasive
      subpopulations. In addition, cathepsin K inhibitors (CatKi) were demonstrated to
      effectively prevent or reduce osteolytic lesions in breast cancers with bone
      metastasis. In comparable to bone metastasis of breast carcinomas, pituitary
      adenomas with sphenoid sinus or clivus invasion lead to osteolytic lesions.
      However, the role of Cathepsin K in sphenoid sinus or clivus invasion of
      pituitary adenomas has not been identified. Therefore, we presume that Cathepsin
      K may have a great importance in sphenoid sinus or clivus invasion and CatKi are
      promising potential therapy for the suppression or prevention of sphenoid sinus
      or clivus invasion of pituitary adenomas.

PMID- 27876138
TI  - Adenomatoid odontogenic tumor: What is the true nature?
AB  - The Adenomatoid odontogenic tumor (AOT) is one of the most controversial benign
      odontogenic tumor, which has been known to the pathologists for the past 100
      years. Since then the history, histogenesis and histopathologic designation of
      AOT remains a matter of debate. Some authors consider it as a true benign
      neoplasm while others consider it as a hamartoma and still others as an
      odontogenic cyst. Here we propose that the AOT should not be considered as a cyst
      because its true cystic nature remains questionable. We hypothesize that when the
      AOT arises from a change in REE covering of the impacted tooth, then it appears
      as cystic in nature & certainly not a true cyst by origin. Further studies on the
      histogenesis are required to change the nomenclature of AOT to adenomatoid
      odontogenic cyst (AOC).

PMID- 27876139
TI  - Conversations between insulin and bone: Potential mechanism of high bone density
      in patients with Berardinelli-Seip Congenital Lipodystrophy.
AB  - Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive
      syndrome characterized by a difficulty storing lipid in adipocytes, low body fat,
      hypertriglyceridemia, and fat liver. The serum leptin is usually very low, and
      serum insulin, as well as HOMAIR (homeostasis model assessment), is very high and
      correlated positively with bone mineral density (BMD). Despite
      deficiency/insufficiency of vitamin D, low body mass index, low daily calcium
      intake, physical inactivity, and menarche at a later age, BSCL patients usually
      have normal or even high BMD. We hypothesize that low leptin and high insulin may
      play a role in this outcome. Understanding the potential pathophysiological
      mechanism of these bone abnormalities will help to clarify the effects of extreme
      insulin resistance in the bone.

PMID- 27876140
TI  - Retinal pigment epithelium cell-derived exosomes: Possible relevance to CNV in
      wet-age related macular degeneration.
AB  - Exosomes are small vesicles that are released by almost every cell type and play
      a crucial role in many physiological and pathological processes associated with
      different diseases. Specifically, they promote angiogenesis in the pathogenesis
      of some diseases. According to previous research, the proteins of exosomes taken
      from the aqueous humor (AH) of patients with wet-age related macular degeneration
      (AMD) may function as a new diagnostic biomarker of AMD, suggesting that exosomes
      may play an important role in the occurrence and development of choroidal
      neovascularization (CNV). Moreover, additional research has revealed that the
      levels of some protein makers of exosomes are up-regulated in aged retinal
      pigment epithelium (RPE) and that drusen and oxidative stress may promote the
      secretion of exosomes derived from RPE cells. Consequently, we hypothesize that
      RPE cell-derived exosomes may be relevant to CNV in wet AMD. If this hypothesis
      is proven correct, future studies based on this link may also help to elucidate
      the molecular mechanisms of wet AMD and to find new therapeutic targets for the
      treatment of AMD.

PMID- 27876141
TI  - SERS as an analytical tool in environmental science: The detection of
      sulfamethoxazole in the nanomolar range by applying a microfluidic cartridge
      setup.
AB  - Sulfamethoxazole (SMX) is a commonly applied antibiotic for treating urinary
      tract infections; however, allergic reactions and skin eczema are known side
      effects that are observed for all sulfonamides. Today, this molecule is present
      in drinking and surface water sources. The allowed concentration in tap water is
      2.10-7 mol L-1. SMX could unintentionally be ingested by healthy people when
      drinking contaminated tap water, representing unnecessary drug intake. To assess
      the quality of tap water, fast, specific and sensitive detection methods are
      required, in which consequence measures for improving the purification of water
      might be initiated in the short term. Herein, the quantitative detection of SMX
      down to environmentally and physiologically relevant concentrations in the
      nanomolar range by employing surface-enhanced Raman spectroscopy (SERS) and a
      microfluidic cartridge system is presented. By applying surface-water samples as
      matrices, the detection of SMX down to 2.2.10-9 mol L-1 is achieved, which
      illustrates the great potential of our proposed method in environmental science.

PMID- 27876142
TI  - Magnetic polyethyleneimine functionalized reduced graphene oxide as a novel
      magnetic solid-phase extraction adsorbent for the determination of polar acidic
      herbicides in rice.
AB  - A novel magnetic polyethyleneimine modified reduced graphene oxide (Fe3O4@PEI
      RGO) had been fabricated based on a self-assemble approach between positive
      charged magnetic polyethyleneimine (Fe3O4@PEI) and negative charged GO sheets via
      electrostatic interaction followed by chemical reduction of GO to RGO. The as
      prepared Fe3O4@PEI-RGO was characterized by transmission electron microscopy
      (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD),
      thermal gravimetric analyzer (TGA), vibrating sample magnetometer (VSM) and zeta
      potential analysis, and then was successfully applied to determine four phenoxy
      acid herbicides and dicamba in rice coupled with high performance liquid
      chromatography (HPLC). As a surface modifier of RGO, PEI not only effectually
      affected the surface property of RGO (e.g. zeta potential), but also changed the
      polarity of RGO and offered anion exchange groups to polar acidic herbicides,
      which would directly influence the type of adsorbed analytes. Compared with
      Fe3O4@PEI, Fe3O4/RGO and Fe3O4@PEI-GO, the as-prepared Fe3O4@PEI-RGO, integrating
      the superiority of PEI and RGO, showed higher extraction efficiency for polar
      acidic herbicides. Besides, the adsorption mechanism was investigated as well. It
      turned out that electrostatic interaction and pi-pi interaction were considered
      to be two major driving force for the adsorption process. Response surface
      methodology (RSM), a multivariate experimental design technique, was used to
      optimize experimental parameters affecting the extraction efficiency in detail.
      Under the optimal conditions, a satisfactory performance was obtained. The
      calibration curves were linear over the concentration ranging from 2 to 300 ng g
      1 with correlation coefficients (r) between 0.9985 and 0.9994. The limits of
      detection (LODs) were in the range of 0.67-2 ng g-1. The recoveries ranged from
      87.41% to 102.52% with relative standard deviations (RSDs) less than 8.94%. Taken
      together, the proposed method was an efficient pretreatment and enrichment
      procedure and could be successfully applied for selective extraction and
      determination of polar acidic herbicides in complex matrices.

PMID- 27876143
TI  - A dispersive liquid-liquid microextraction using a switchable polarity dispersive
      solvent. Automated HPLC-FLD determination of ofloxacin in chicken meat.
AB  - In this article, dispersive liquid-liquid microextraction (DLLME), based on the
      use of so-called switchable polarity dispersive solvent (SPDS) for
      microextraction, is presented for the first time. The new extraction technique
      makes use of a mixture of extraction solvent (dichloromethane) and the SPDS
      (acrylic acid). This mixture is injected into the aqueous sample solution, which
      was previously fortified with the alkaline agent (NaOH). The SPDS is dissolved in
      aqueous phase and a cloudy solution consisting of fine droplets of extraction
      solvent fully dispersed in the aqueous phase is observed. Simultaneously, as a
      consequence of the fast neutralization reaction, the SPDS investigated is
      converted into water-soluble salt and phase separation is achieved because the
      SPDS switches its polarity. Conversion of the SPDS excludes the negative
      influence of the conventional dispersive solvents used in DLLME on the solubility
      of target analytes in aqueous phase and, as a result, increases the DLLME
      efficiency. The proposed extraction technique was automated based on a flow
      system and coupled with high performance liquid chromatography system with
      fluorescence detection (HPLC-FLD) and demonstrated by the determination of
      ofloxacin (OFLX) in chicken meat samples. This analytical task was used as a
      proof-of-concept example. The automated method includes on-line ultrasound
      assisted solid-liquid extraction of OFLX from chicken meat samples followed by
      DLLME using SPDS, solvent exchange and the determination by HPLC-FLD. Under the
      optimal conditions, the detector response for OFLX was linear in concentration
      range of 6.10-9 - 5.10-7 mol L-1. The limit of detection, calculated from a blank
      test based on 3sigma, was 2.10-9 mol L-1.

PMID- 27876144
TI  - In-tip nanoreactors for cancer cells proteome profiling.
AB  - Mass spectrometry (MS)-based proteome profiling is essential for molecular
      diagnostics in modern biomedical study. To date, sample preparation including
      protein extraction and proteolysis is still very challenging and lack of
      efficiency. Recently tips-based sample preparation protocols exhibit strong
      potentials to achieve the goal of "a proteome in an hour". However, in-tip
      proteolysis is still rarely reported and far from ideal for dealing with complex
      bio-samples. In this work, nanoreactors encapsulated micropipette tips were
      demonstrated as high performance devices for fast (~minutes) and multiplexing
      proteolysis to assist the profiling of cancer cells proteome. Nanoporous silica
      materials with controlled pore size and surface chemistry were prepared as
      nanoreactors and encapsulated in micropipette tips for efficient in situ
      proteolysis. The as-constructed device showed desirable sensitivity (LOD of 0.204
      +/- 0.008 ng/MUL and LOQ of 0.937 +/- 0.055 ng/MUL), selectivity, stability (two
      months under -20  degrees C), reusability (at least 10 times), and little memory
      effect in MS based bottom-up proteomic analysis. It was used for comprehensive
      protein mapping from cancer cell lines. The number of identified proteins was
      increased by 18%, 22%, 52%, and 52% dealing with HepG2, F56, MCF7, and HCCLM3
      cancer cells, compared to traditional in-solution proteolysis based bottom-up
      proteomic strategy. With the enhanced performance, our work built a novel,
      efficient and miniaturized platform for facile proteomic sample preparation,
      which is promising for advanced biomarkers discovery in biomedical study.

PMID- 27876145
TI  - Entropy-driven reactions in living cells for assay let-7a microRNA.
AB  - Imaging of microRNA (miRNA) in living cells could facilitate the monitoring of
      the expression and distribution of miRNA and research on miRNA-related diseases.
      Given the low expression levels and even down-regulation of cellular miRNA that
      is associated with some diseases, enzyme-free amplification strategies are
      imperative for intracellular miRNA assay. In this work, we report an entropy
      driven reaction for amplification assay miRNA with a detection limit of 0.27 pM.
      The resulting signal amplification provides excellent recognition and signal
      enhancement of specific miRNAs in living cells. This method supplies accurate
      information regarding cellular miRNA-related biological events and provides a new
      tool for highly sensitive and simultaneous imaging of multiple low-level
      biomarkers, thereby improving the accuracy of early disease diagnosis.

PMID- 27876146
TI  - Vertical-flow paper SERS system for therapeutic drug monitoring of flucytosine in
      serum.
AB  - A number of life-saving drugs require therapeutic drug monitoring (TDM) for safe
      and effective use. Currently, however, TDM is performed using sophisticated
      analytical techniques relegated to central labs, increasing the cost per test and
      time to answer. Here, using a novel vertical flow membrane system with inkjet
      printed surface enhanced Raman sensors, along with a portable spectrometer, we
      demonstrate a low cost and easy to use device to quantify levels of flucytosine,
      an antifungal that requires TDM for effective patient care, from undiluted human
      serum. To our knowledge, this work represents the first report of a passive
      vertical flow sample cleanup method with surface enhanced Raman detection. We
      first investigated and optimized the parameters of the vertical flow system for
      the detection of flucytosine in spiked serum samples. Then, using an optimized
      vertical-flow system utilizing nitrocellulose membranes and a paper SERS sensor,
      we achieved detection of down to 10 MUg mL-1 flucytosine in undiluted serum, with
      quantitative detection across the entire therapeutic range. This system reduces
      the assay time to about 15 min, far quicker than the current gold standards. We
      anticipate that this novel system will enable near-patient therapeutic drug
      monitoring, leading to the safe and effective administration of a number of life
      saving drugs. Furthermore, it will spawn the development of SERS detection
      systems capable of separating target analytes from real-world biological
      matrices.

PMID- 27876147
TI  - Facile fabrication of hydrophilic PAA-Ti/TiO2 nanocomposite for selective
      enrichment and detection of phosphopeptides from complex biological samples.
AB  - Highly selective enrichment of trace phosphorylated proteins or peptides from
      complex biological samples is of profound significance for the discovery of
      disease biomarkers in biological systems. In this study, a novel affinity
      material has been synthesized to improve the enrichment specificity for
      phosphopeptides by using PAAS as coupling molecule. In the resulting materials,
      highly abundant titanium is available for selective enrichment of
      phosphopeptides, with plenty of carboxylate groups that can inhibit nonspecific
      adsorption. The enrichment results demonstrated that the hydrophilic PAA-Ti/TiO2
      composite possesses excellent selectivity for phosphopeptides even at a very low
      molar ratio of phosphopeptides/non-phosphopeptides (1:1000), extreme sensitivity
      (the detection limit was at the fmol level), and high recovery of phosphopeptides
      (as high as 78%). Moreover, the as-prepared nanocomposite provides effective
      enrichment of phosphopeptides from real samples (mouse liver), showing great
      potential in the detection of low-abundance phosphopeptides in biological
      samples.

PMID- 27876149
TI  - Gas chromatographic determination of perfluorocarboxylic acids in aqueous samples
      - A tutorial review.
AB  - Determination of perfluorocarboxylic acids (PFCAs) by gas chromatography (GC) has
      been undertaken since 1980. However, only small number of studies can be found in
      the literature due to the major drawbacks associated with the GC determination of
      PFCAs such as high detection limits, a small range of analytes, long analysis
      time, and laborious derivatization prior to chromatographic separation. Liquid
      chromatography-tandem mass spectrometry (LC-MS2) can overcome these limitations
      of GC, and therefore has become the method of choice for the determination of
      PFCAs since 2001. Nevertheless, GC as a low-cost and commonly available
      analytical technique should not be ignored because of its inherent advantage over
      LC to identify PFCA isomers in environmental and biological matrices owing to its
      high-resolution power. In addition, GC provides an opportunity to crosscheck LC
      MS2 results that are often suspicious due to background contamination. This
      tutorial provides an overview of GC methods that have been used for the
      determination of PFCAs after derivatization. Moreover, performance
      characteristics of GC-MS are compared with that of LC-MS2. PFCAs in aqueous
      samples were determined by both analytical techniques, and two sets of
      measurements were compared using the Bland-Altman plot. For both methods, reasons
      for false-positive and false-negative results (overestimation and underestimation
      of the PFCA concentration, respectively) are discussed, and accordingly some
      advice is offered on how to avoid erroneous results. Finally, major applications
      of GC and its future perspectives for the determination of PFCAs are discussed.

PMID- 27876148
TI  - Fc-specific biotinylation of antibody using an engineered photoactivatable Z
      Biotin and its biosensing application.
AB  - The development of a site-specific and covalent attachment methodology is crucial
      for antibody-biotin conjugates to preserve the antigen-binding ability of
      antibodies and yield homogeneous products. In this study, an engineered
      photoactivatable Z-domain variant [an UV-active amino acid benzoylphenylalanine
      (Bpa) was genetically incorporated into the Z-domain] carrying one biotin
      molecule (ZBpa-Biotin) was prepared by employing aminoacyl-tRNA
      synthetase/suppressor tRNA and Avitag/BirA techniques. The site-specific and
      covalent attachment of IgG-biotin conjugates, viz. photo-biotinylated IgG, was
      successfully achieved after UV exposure by combining the inherent Fc-binding
      capability of the Z-domain with the formation of covalent bond by the photo
      crosslinker. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis assay
      showed that more than 90% of IgGs conjugated with ZBpa-Biotin molecules suffered
      3 h UV irradiation. Further pepsin digestion analysis confirmed that the ZBpa
      Biotin was conjugated to the Fc fragment of IgG without interference. We took the
      tumor biomarker carcinoembryoic antigen (CEA) as model to evaluate the detection
      efficiency of the site-specific photo-biotinylated IgG in biosensing application
      using surface plasmon resonance (SPR) technology. The photo-biotinylated IgG
      coated surface gave a limit of detection (LOD) of 2 ng mL-1, is 5-fold lower than
      that of the randomly NHS-biotinylated IgG (10 ng mL-1). Given that the
      (strept)avidin-biotin complex is extensively used in immunoassays, the proposed
      method for biotinylated IgG provides a powerful approach to further expand
      related applications.

PMID- 27876150
TI  - Coupling hybridization chain reaction with DNAzyme recycling for enzyme-free and
      dual amplified sensitive fluorescent detection of methyltransferase activity.
AB  - Aberrant DNA methylation originated from changes in DNA methyltransferase
      activity can lead to many genetic diseases and tumor types, and the monitoring of
      methyltransferase activity is thus of great importance in disease diagnosis and
      drug screening. In this work, by combing hybridization chain reaction (HCR) and
      metal ion-dependent DNAzyme recycling, we have developed a convenient enzyme-free
      signal amplification strategy for highly sensitive detection of DNA adenine
      methyltransferase (Dam MTase) activity and its inhibitors. The Dam MTase-induced
      methylation and subsequent cleavage of the methylated hairpin DNA probes by DpnI
      endonuclease lead to the release of ssDNA triggers for HCR formation of many Mg2+
      dependent DNAzymes, in which the fluorescently quenched substrate sequences are
      catalytically and cyclically cleaved by Mg2+ to generate remarkably amplified
      fluorescent signals for highly sensitive detection of Dam MTase at 7.23 * 10-4
      U/mL. In addition, the inhibition of different drugs to Dam MTase activity can
      also be evaluated with the developed method. With the advantages of simplicity
      and significant signal amplification over other common methods, the demonstrated
      biosensing approach thus offers great potential for highly sensitive detection of
      various methyltransferases and provides a convenient platform for drug screening
      for therapeutic applications.

PMID- 27876153
TI  - Correction.

PMID- 27876154
TI  - Corrigendum to Automatic and controlled stimulus processing in conflict tasks:
      Superimposed diffusion processes and delta functions [Cogn. Psychol. 78 (2015)
      148-174].

PMID- 27876155
TI  - A Dual Hit Model for Dopamine in Schizophrenia.

PMID- 27876156
TI  - Withdrawal.

PMID- 27876151
TI  - Identification of an Epitope from Adenine Nucleotide Translocator 1 That Induces
      Inflammation in Heart in A/J Mice.
AB  - Heart failure, a leading cause of death in humans, can emanate from myocarditis.
      Although most individuals with myocarditis recover spontaneously, some develop
      chronic dilated cardiomyopathy. Myocarditis may result from both infectious and
      noninfectious causes, including autoimmune responses to cardiac antigens. In
      support of this notion, intracellular cardiac antigens, like cardiac myosin heavy
      chain-alpha, cardiac troponin-I, and adenine nucleotide translocator 1 (ANT1),
      have been identified as autoantigens in cardiac autoimmunity. Herein, we
      demonstrate that ANT1 can induce autoimmune myocarditis in A/J mice by generating
      autoreactive T cells. We show that ANT1 encompasses multiple immunodominant
      epitopes (namely, ANT1 21-40, ANT1 31-50, ANT1 171-190, and ANT1 181-200).
      Although all four peptides induce comparable T-cell responses, only ANT1 21-40
      was found to be a major myocarditogenic epitope in immunized animals. The
      myocarditis-inducing ability of ANT1 21-40 was associated with the generation of
      T cells producing predominantly IL-17A, and the antigen-sensitized T cells could
      transfer the disease to naive recipients. These data indicate that cardiac
      mitochondrial proteins can be target autoantigens in myocarditis, supporting the
      notion that the antigens released as a result of primary damage may contribute to
      the persistence of chronic inflammation through autoimmunity.

PMID- 27876152
TI  - The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury
      Models.
AB  - Neural input to the immune system can alter its ability to clear pathogens
      effectively. Patients suffering mild traumatic brain injury (mTBI) have shown
      reduced rates of pneumonia and a murine model replicated these findings, with
      better overall survival of TBI mice compared with sham-injured mice. To further
      investigate the mechanism of improved host response in TBI mice, this study
      developed and characterized a mild tail trauma model of similar severity to mild
      TBI. Both mild tail trauma and TBI induced similar systemic changes that
      normalized within 48 hours, including release of substance P. Examination of
      tissues showed that injuries are limited to the target tissue (ie, tail in tail
      trauma, brain in mTBI). Pneumonia challenge showed that mild TBI mice showed
      improved immune responses, characterized by the following: i) increased survival,
      ii) increased pulmonary neutrophil recruitment, iii) increased bacterial
      clearance, and iv) increased phagocytic cell killing of bacteria compared with
      tail trauma. Administration of a neurokinin-1-receptor antagonist to block
      substance P signaling eliminated the improved survival of mTBI mice. Neurokinin-1
      receptor antagonism did not alter pneumonia mortality in tail trauma mice. These
      data show that immune benefits of trauma are specific to mTBI and that tail
      trauma is an appropriate control for future studies aimed at elucidating the
      mechanisms of improved innate immune responses in mTBI mice.

PMID- 27876157
TI  - Addressing Cognitive Deficits in Schizophrenia: Toward a Neurobiologically
      Informed Approach.

PMID- 27876158
TI  - Is Bicarbonate Therapy Useful?
AB  - Despite concerns about the negative effects of metabolic acidosis, there is
      minimal evidence that sodium bicarbonate administration is an effective
      treatment. In addition, sodium bicarbonate therapy is associated with many
      adverse effects, including paradoxic intracellular acidosis, hypokalemia,
      hypocalcemia, hypernatremia, and hyperosmolality. Definitive recommendations
      regarding bicarbonate therapy are challenging as there is little high-quality
      evidence available. In most clinical scenarios of metabolic acidosis, treatment
      efforts should focus on resolution of the underlying cause, and sodium
      bicarbonate therapy should be used with caution, if at all. An exception to this
      is kidney disease, wherein sodium bicarbonate therapy may have a valuable role.

PMID- 27876159
TI  - Natural radionuclides in lichens, mosses and ferns in a thermal power plant and
      in an adjacent coal mine area in southern Brazil.
AB  - The radio-elements 234U, 235U, 238U, 230Th, 232Th and 210Po were characterized in
      lichens, mosses and ferns species sampled in an adjacent coal mine area at
      Figueira City, Parana State, Brazil, due to their importance for the assessment
      of human exposure related to the natural radioactivity. The coal is geologically
      associated with a uranium deposit and has been used as a fossil fuel in a thermal
      power plant in the city. Samples were initially prepared at LABIDRO (Isotopes and
      Hydrochemistry Laboratory), UNESP, Rio Claro (SP), Brazil. Then, alpha
      spectrometry after several radiochemical steps was used at the Applied Nuclear
      Physics Laboratories, University of Seville, Seville, Spain, for measuring the
      activity concentration of the radionuclides. It was 210Po the radionuclide that
      most bio-accumulates in the organisms, reaching the highest levels in mosses. The
      ferns species were less sensitive as bio-monitor than the mosses and lichens,
      considering polonium in relation to other radionuclides. Fruticose lichens
      exhibited lower polonium content than the foliose lichens sampled in the same
      site. Besides biological features, environmental characteristics also modify the
      radio-elements absorption by lichens and mosses like the type of vegetation
      covering these organisms, their substrate, the prevailing wind direction,
      elevation and climatic conditions. Only 210Po and 238U correlated in ferns and in
      soil and rock materials, being particulate emissions from the coal-fired power
      plant the most probable U-source in the region. Thus, the biomonitors used were
      able to detect atmospheric contamination by the radionuclides monitored.

PMID- 27876160
TI  - An analysis of the radioactive contamination due to radon in a granite processing
      plant and its decontamination by ventilation.
AB  - This work focuses on studying concentration distribution of 222Rn radioisotope in
      a granite processing plant. Using Computational Fluid Dynamic Techniques (CFD),
      the exposure of the workers to radiation was assessed and, in order to minimise
      this exposure, different decontamination scenarios using ventilation were
      analysed. Natural ventilation showed not sufficient to maintain radon
      concentration below acceptable limits, so a forced ventilation was used instead.
      Position of the granite blocks also revealed as a determining factor in the
      radioactive level distribution. Thus, a correct layout of the stored material and
      an adequate ventilation system can guarantee free of exposure to radiation zones
      within the studied workshop. This leads to a drastic fall in the exposure of the
      workers and consequently minimises their risk of developing aggressive illness
      like lung cancer.

PMID- 27876161
TI  - Intermaxillary fixation with intraoral plates and screws.

PMID- 27876162
TI  - Predictive factors of hospital stay in patients with odontogenic maxillofacial
      infections: the role of C-reactive protein.
AB  - To investigate whether clinical or laboratory variables on admission of patients
      with odontogenic infections are associated with a severe clinical course and a
      prolonged hospital stay, we hypothesised that specific factors such as the serum
      concentration of C-reactive protein (CRP) may act as predictors of the duration
      of stay. We designed a prospective patient-oriented study that included all those
      treated for maxillofacial infections of odontogenic origin in the Oral and
      Maxillofacial Surgery Department of Northampton General Hospital between November
      2013 and December 2014. A total of 71 were enrolled. We found that the
      concentration of CRP was a significant predictor of hospital stay (p=0.01). Its
      measurement on admission can predict the likely duration of stay of these
      patients and enable beds to be managed more efficiently.

PMID- 27876164
TI  - Measuring the environmental sustainability performance of global supply chains: A
      multi-regional input-output analysis for carbon, sulphur oxide and water
      footprints.
AB  - Measuring the performance of environmentally sustainable supply chains instead of
      chain constitute has become a challenge despite the convergence of the
      underlining principles of sustainable supply chain management. This challenge is
      exacerbated by the fact that supply chains are inherently dynamic and complex and
      also because multiple measures can be used to characterize performances. By
      identifying some of the critical issues in the literature regarding performance
      measurements, this paper contributes to the existing body of literature by
      adopting an environmental performance measurement approach for economic sectors.
      It uses economic sectors and evaluates them on a sectoral level in specific
      countries as well as part of the Global Value Chain based on the established
      multi-regional input-output (MRIO) modeling framework. The MRIO model has been
      used to calculate direct and indirect (that is supply chain or upstream)
      environmental effects such as CO2, SO2, biodiversity, water consumption and
      pollution to name just a few of the applications. In this paper we use MRIO
      analysis to calculate emissions and resource consumption intensities and
      footprints, direct and indirect impacts, and net emission flows between
      countries. These are exemplified by using carbon emissions, sulphur oxide
      emissions and water use in two highly polluting industries; Electricity
      production and Chemical industry in 33 countries, including the EU-27, Brazil,
      India and China, the USA, Canada and Japan from 1995 to 2009. Some of the
      highlights include: On average, direct carbon emissions in the electricity sector
      across all 27 member states of the EU was estimated to be 1368 million tons and
      indirect carbon emissions to be 470.7 million tons per year representing 25.6% of
      the EU-27 total carbon emissions related to this sector. It was also observed
      that from 2004, sulphur oxide emissions intensities in electricity production in
      India and China have remained relatively constant at about 62.8 gSOx/,
      respectively, $ and 84.4 gSOx/$ although being higher than in other countries. In
      terms of water use, the high water use intensity in China (1040.27 L/$) and India
      (961.63 L/$), which are among the highest in the sector in the electricity sector
      is exacerbated by both countries being ranked as High Water Stress Risk
      countries. The paper also highlights many advantages of the MRIO approach
      including: a 15-year time series study (which provides a measurement of
      environmental performance of key industries and an opportunity to assess
      technical and technological change during the investigated time period), a supply
      chain approach that provides a consistent methodological framework and accounts
      for all upstream supply chain environmental impacts throughout entire global
      supply chains. The paper also discusses the implications of the study to
      environmental sustainability performance measurement in terms of the level of
      analysis from a value chain hierarchy perspective, methodological issues,
      performance indicators, environmental exchanges and policy relevance.

PMID- 27876163
TI  - Process control charts in infection prevention: Make it simple to make it happen.
AB  - BACKGROUND: Quality improvement is central to Infection Prevention and Control
      (IPC) programs. Challenges may occur when applying quality improvement
      methodologies like process control charts, often due to the limited exposure of
      typical IPs. Because of this, our team created an open-source database with a
      process control chart generator for IPC programs. The objectives of this report
      are to outline the development of the application and demonstrate application
      using simulated data. METHODS: We used Research Electronic Data Capture (REDCap
      Consortium, Vanderbilt University, Nashville, TN), R (R Foundation for
      Statistical Computing, Vienna, Austria), and R Studio Shiny (R Foundation for
      Statistical Computing) to create an open source data collection system with
      automated process control chart generation. We used simulated data to test and
      visualize both in-control and out-of-control processes for commonly used metrics
      in IPC programs. RESULTS: The R code for implementing the control charts and
      Shiny application can be found on our Web site (https://github.com/ul-research
      support/spcapp). Screen captures of the workflow and simulated data indicating
      both common cause and special cause variation are provided. CONCLUSIONS: Process
      control charts can be easily developed based on individual facility needs using
      freely available software. Through providing our work free to all interested
      parties, we hope that others will be able to harness the power and ease of use of
      the application for improving the quality of care and patient safety in their
      facilities.

PMID- 27876166
TI  - [8th congress on Real World Data, Paris, June 2nd 2016].

PMID- 27876167
TI  - [18F]-Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis, Treatment
      Stratification, and Monitoring of Patients with Retroperitoneal Fibrosis: A
      Prospective Clinical Study.
AB  - BACKGROUND: The ability to distinguish malignant from benign retroperitoneal
      fibrosis (RPF) and to select patients who are likely to respond to steroid
      treatment using a noninvasive test would be a major step forward in the
      management of patients with RPF. OBJECTIVE: To prospectively evaluate the
      potential of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) to
      improve clinical decision-making and management of RPF. DESIGN, SETTING, AND
      PARTICIPANTS: A total of 122 RPF patients were assessed and managed by a
      multidisciplinary RPF service between January 2012 and December 2015. Of these,
      78 patients underwent 101 FDG-PET scans, as well as computed tomography and blood
      tests. Management was based on the findings from these investigations. Median
      follow-up was 16 mo. RESULTS AND LIMITATIONS: Of the 24 patients with negative
      [18F]-FDG-PET, none (0%) had malignancy on biopsy (negative predictive value
      100%). [18F]-FDG-PET identified malignancy in 4/4 patients (100%) before biopsy.
      All four patients had highly avid PET (maximum standardised uptake value >=4)
      with atypical avidity distribution. [18F]-FDG-PET revealed avidity in 19/38
      patients (50%) with normal inflammatory markers and no avidity in 10/63 patients
      (16%) with raised marker levels. Patients with highly avid PET were significantly
      more likely to respond to steroids compared to those with low avidity (9/11 [82%]
      vs 3/24 [12%]; p<0.01) or negative PET (9/11 [82%] vs 0/14 [0%]; p<0.01).
      Limitations include the small number of patients and the predominance of tertiary
      referrals, which may represent patients with particularly problematic RPF.
      CONCLUSIONS: This study has established a promising role for [18F]-FDG-PET in
      optimising and individualising the treatment of RPF. PATIENT SUMMARY: This study
      shows that [18F]-fluorodeoxyglucose positron emission tomography scans could
      reduce the need for biopsy in patients with retroperitoneal fibrosis (RPF). This
      technique can distinguish cancer from noncancerous RPF, and may be better than
      blood tests in assessing and monitoring RPF. It also appears to predict a
      patient's response to steroids, which should allow more individualised treatment.

PMID- 27876168
TI  - Re: Daniel E. Spratt, Hebert A. Vargas, Zachary S. Zumsteg, et al. Patterns of
      Lymph Node Failure after Dose-escalated Radiotherapy: Implications for Extended
      Pelvic Lymph Node Coverage. Eur Urol 2017;71:37-43: A Step Forward in the Era of
      Functional Imaging?

PMID- 27876170
TI  - Corrigendum to "Determinants of brain-derived neurotrophic factor (BDNF) in
      umbilical cord and maternal serum" [Psychoneuroendocrinology 63 (2016) 191-197].

PMID- 27876165
TI  - Application of Research Domain Criteria to childhood and adolescent impulsive and
      addictive disorders: Implications for treatment.
AB  - The Research Domain Criteria (RDoC) initiative provides a large-scale,
      dimensional framework for the integration of research findings across traditional
      diagnoses, with the long-term aim of improving existing psychiatric treatments. A
      neurodevelopmental perspective is essential to this endeavor. However, few papers
      synthesizing research findings across childhood and adolescent disorders exist.
      Here, we discuss how the RDoC framework may be applied to the study of childhood
      and adolescent impulsive and addictive disorders in order to improve
      neurodevelopmental understanding and to enhance treatment development. Given the
      large scope of RDoC, we focus on a single construct highly relevant to addictive
      and impulsive disorders - initial responsiveness to reward attainment. Findings
      from genetic, molecular, neuroimaging and other translational research
      methodologies are highlighted.

PMID- 27876169
TI  - [Bacillus isolates from rhizosphere of cacti improve germination and bloom in
      Mammillaria spp. (Cactaceae)].
AB  - Cacti are the most representative vegetation of arid zones in Mexico where
      rainfall is scarce, evapotranspiration is high and soil fertility is low. Plants
      have developed physiological strategies such as the association with
      microorganisms in the rhizosphere zone to increase nutrient uptake. In the
      present work, four bacterial isolates from the rhizosphere of Mammillaria
      magnimamma and Coryphantha radians were obtained and named as QAP3, QAP19, QAP22
      and QAP24, and were genetically identified as belonging to the genus Bacillus,
      exhibiting in vitro biochemical properties such as phosphate solubilization,
      indoleacetic acid production and ACC deaminase activity related to plant growth
      promotion, which was tested by inoculating M. magnimamma seeds. It was found that
      all isolates increased germination from 17 to 34.3% with respect to the
      uninoculated control seeds, being QAP24 the one having the greatest effect,
      accomplishing the germination of viable seeds (84.7%) three days before the
      control seeds. Subsequently, the inoculation of Mammillari zeilmanniana plants
      with this isolate showed a positive effect on bloom, registering during two
      months from a one year period, an increase of up to 31.0% in the number of
      flowering plants compared to control plants. The characterized Bacillus spp.
      isolates have potential to be used in conservation programs of plant species from
      arid zones.

PMID- 27876171
TI  - Cardiovascular Risk Factor Management Performance in Canada and the United
      States: A Systematic Review.
AB  - BACKGROUND: Comparative cardiovascular risk factor care across North America is
      unknown. We aimed to determine current performance in Canada and the United
      States (US). METHODS: A systematic review was conducted of Medline and EMBASE (to
      June 1, 2014). Eligible studies reported on screening, awareness, treatment, or
      control rates for hypertension, dyslipidemia, diabetes, and smoking. Categorical
      performance 'ratings' on the basis of the most successful US health plans were
      used to classify rates as suboptimal (< 50%), below target (50%-70%), above
      target (70%-90%), or optimal (> 90%). RESULTS: A total of 127 studies reporting
      on 10,510,324 individuals across North America were included. Hypertension
      awareness (84.3%) and treatment (82.0%) rates in Canada and the US (82.7% and
      75.6%, respectively) were above target, whereas control in both nations was below
      target (68.1% vs 51.8%, respectively). Canadian awareness, treatment, and control
      rates for dyslipidemia (42.7%, 40.9%, and 41.5%, respectively) were suboptimal,
      and American indicators were generally below target (61.5%, 43.0%, and 63.6%,
      respectively). Canada and the US showed diabetes awareness (88.2% vs 86.8%) and
      treatment rates (82.3% vs 82.5%) above target. However, glucose control was
      suboptimal in Canada (35.3%), and below target in the US (58.8%). There was a
      modest decline in absolute smoking prevalence rates in Canada from 1999 to 2013
      (25.2% to 14.6%). Screening for tobacco use (72.2%) and counselling rates (73.8%)
      in the US were above target. CONCLUSIONS: Substantial variation exists in
      cardiovascular risk factor care across North America. Standardized reporting,
      dissemination of practice guidelines, and setting explicit goal-directed targets
      for performance might facilitate improvement.

PMID- 27876172
TI  - Cystatin C Versus Creatinine for GFR Estimation in CKD Due to Heart Failure.

PMID- 27876173
TI  - Automated detection of bone metastatic changes using serial CT scans.
AB  - Bone metastases resulting from a primary tumor invasion to the bone are common
      and cause significant morbidity in advanced cancer patients. Although the
      detection of bone metastases is often straightforward, it is difficult to
      identify their spread and track their changes, particularly in early stages. This
      paper presents a novel method that automatically finds the changes in appearance
      and the progress of bone metastases using longitudinal CT images. In contrast to
      previous methods based on nodule detection within a specific bone site in an
      individual CT scan, the approach in the present study is based on the subtraction
      between two registered CT volumes. The volumes registered using the proposed
      weighted-Demons registration and symmetric warping were subtracted with
      minimizing noise, and the Jacobian and false positive suppressions were performed
      to reduce false alarms. The proposed method detects the changes in bone
      metastases within 3min for entire chest bone structures covering the spine, ribs,
      and sternum. The method was validated based on 3-fold cross validation using the
      radiologists' markings of 459 lesions in 24 subjects and was performed with a
      sensitivity of 92.59%, a false positive volume of 2.58%, and 9.71 false positives
      per patient. Note that 113 lesions (24%) missed by the radiologists were
      identified by the present system and confirmed to be true metastases. Indeed,
      three patients diagnosed initially as normal, having no metastatic difference, by
      radiologists were found to be abnormal using the proposed system. Automatic
      detection method of bone metastatic changes in the entire chest bone was
      developed. Weighted Demons, symmetric warping, following false positive
      suppressions, and their parallel computing implementation enabled precise and
      fast computation of delicate changes in serial CT scans. The cross validation
      proved that this method can be quite useful for assisting radiologists in sensing
      minute metastatic changes from early stage.

PMID- 27876174
TI  - Artificial neural networks: Predicting head CT findings in elderly patients
      presenting with minor head injury after a fall.
AB  - OBJECTIVES: To construct an artificial neural network (ANN) model that can
      predict the presence of acute CT findings with both high sensitivity and high
      specificity when applied to the population of patients>=age 65years who have
      incurred minor head injury after a fall. METHODS: An ANN was created in the
      Python programming language using a population of 514 patients >= age 65 years
      presenting to the ED with minor head injury after a fall. The patient dataset was
      divided into three parts: 60% for "training", 20% for "cross validation", and 20%
      for "testing". Sensitivity, specificity, positive and negative predictive values,
      and accuracy were determined by comparing the model's predictions to the actual
      correct answers for each patient. RESULTS: On the "cross validation" data, the
      model attained a sensitivity ("recall") of 100.00%, specificity of 78.95%, PPV
      ("precision") of 78.95%, NPV of 100.00%, and accuracy of 88.24% in detecting the
      presence of positive head CTs. On the "test" data, the model attained a
      sensitivity of 97.78%, specificity of 89.47%, PPV of 88.00%, NPV of 98.08%, and
      accuracy of 93.14% in detecting the presence of positive head CTs. CONCLUSIONS:
      ANNs show great potential for predicting CT findings in the population of
      patients >= 65 years of age presenting with minor head injury after a fall. As a
      good first step, the ANN showed comparable sensitivity, predictive values, and
      accuracy, with a much higher specificity than the existing decision rules in
      clinical usage for predicting head CTs with acute intracranial findings.

PMID- 27876175
TI  - [Anti-HMG-CoA reductase necrotizing myopathy: A report of 4 cases].
AB  - INTRODUCTION: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody
      associated necrotizing autoimmune myopathy has been recently described (2011).
      This myopathy is distinct from statin toxic myopathy. Our objective is to report
      on the clinical and para-clinical characteristics of this myopathy and to show
      the difficulties of therapeutic care. CASE REPORTS: We describe 4 cases of
      patients followed-up in Brittany, France. All data have been analyzed
      retrospectively. The mean age of our patients was 59.5 years, with a sex ratio of
      1. The clinical presentation was homogeneous, with a subacute painful proximal
      and symmetrical weakness, without extra-muscular involvement. Other presentations
      have been described (including pseudo-dystrophic presentation). All patients had
      a previous statin medication (mean duration of 3.75 years) although this criteria
      is not a requisite. All patients had high levels of creatine kinase and abnormal
      electromyographic examination. The pathological pattern on muscular biopsy was a
      necrotizing myopathy without significant inflammatory cells infiltration. Cardio
      respiratory function was normal and no associated neoplasia was found. Over the
      follow-up, we observed a marked corticosteroid-dependence, not improved by
      immunosuppressive drugs (azathioprine and methotrexate). The benefit of
      intravenous immunoglobulin was clear with, sometimes, prolonged responses.
      CONCLUSION: An early diagnosis of this myopathy is necessary in order to
      introduce an immunotherapy associated with a close monitoring. The therapeutic
      strategy (within which the stead of intravenous immunoglobulin seems increased)
      remains to be defined and long-term prospective studies are thus needed.

PMID- 27876176
TI  - [An aortic abnormality].

PMID- 27876177
TI  - The Evolution of Child Neurology Training.

PMID- 27876178
TI  - Hydranencephaly in Monochorionic-Diamniotic Twins.

PMID- 27876180
TI  - Gray-scale intravascular ultrasound sheds light on the importance of vasa vasorum
      in unstable coronary plaque.

PMID- 27876179
TI  - Prevalence and Risk Factors of Peri-ictal Autonomic Changes in Children With
      Temporal Lobe Seizures.
AB  - BACKGROUND: We determined the prevalence of signs and symptoms of autonomic
      dysfunction in seizures of temporal lobe onset in children. METHODS: We evaluated
      the prevalence and risk factors of peri-ictal autonomic changes in temporal lobe
      onset seizures in children from a single-center pediatric epilepsy monitoring
      unit between June 1, 2009 and October 31, 2013. Age, gender, epilepsy etiology,
      current antiepileptic drug therapy, ictal electroencephalographic lateralization,
      brain magnetic resonance imaging results, and the presence of generalized tonic
      clonic seizures over the preceding year were recorded from medical record review.
      RESULTS: Forty-nine children were identified (55% male, median age 10.1 years
      [interquartile range 5.5 to 13.9 years]). Overall, peri-ictal autonomic changes
      were observed in 32 of 49 patients (66%) and 91 of 172 evaluated seizures (53%).
      Tachycardia (51%), oxygen desaturation (33%), and salivation (27%) were the most
      frequent autonomic changes identified. Bradycardia occurred in one patient (2%).
      CONCLUSIONS: Among pediatric patients with temporal lobe seizures, peri-ictal
      autonomic changes are frequent yet seldom require intervention.

PMID- 27876181
TI  - Analysis of suboptimal stent deployment using intravascular ultrasound and
      coronary pressure pullback measurement.
AB  - BACKGROUND: There are some cases in whom a sufficient improvement in fractional
      flow reserve (FFR) could not be achieved even if anatomical results indicated
      satisfactory stent deployment. We investigated the relation of abnormal findings
      between intravascular ultrasound (IVUS) and coronary pressure pullback
      measurement (CP-PB). METHODS: IVUS and CP-PB were investigated after stent
      deployment in 60 vessels in 53 patients. CP-PB criterion for adequate stent
      deployment was defined as a ratio of coronary pressure at the stent distal edge
      to the proximal edge (Psd/Psp) that is greater than 0.95. RESULTS: Residual
      pressure gradient across the stent which was indicated by Psd/Psp<=0.95 was
      present in 11 (18%), and four of them were caused by insufficient stent expansion
      (incomplete apposition and asymmetric dilation), and five of them were caused by
      issues with stent edge (edge dissection and incomplete coverage of the plaques).
      Insufficient FFR recovery which was recorded at distal part of target vessel was
      present in 10 (17%), and the main causes corresponded to inadequate stent
      deployment in half of the lesions, and presence of residual lesion at a non-stent
      segment in the other half. There were six lesions in whom Psd/Psp was <=0.95 but
      FFR was >=0.80. Disagreement between IVUS and CP-PB findings was seen in 12
      (20%). CONCLUSIONS: Residual pressure gradient across the stent can reflect not
      only an insufficient stent expansion but also issues with stent edges. The
      decision of optimum stent deployment as assessed by IVUS and CP-PB was mismatched
      in 20% of cases, therefore careful attention should be paid to decoding the CP-PB
      findings.

PMID- 27876182
TI  - Colonization of Black Smokers by Hyperthermophilic Microorganisms.
AB  - Newly erupted black smokers (hydrothermal vent chimneys) are sterile during their
      formation, but they house hyperthermophiles in substantial amounts in later
      stages. No hard data exist on the mechanisms by which hyperthermophiles colonize
      newly erupted black smokers. Here I propose a scenario - based on various
      experimental data - for how hyperthermophiles colonize black smokers.
      Hyperthermophiles which are present in cold sea water in minute amounts are
      transferred by chance to the outside of black smokers and react within seconds to
      the high temperature by very fast movements. After reaching an optimal
      temperature region they scan the surface via a zigzag seek-movement and adhere
      via their flagella at a suitable place, building up biofilms.

PMID- 27876183
TI  - Electroconvulsive therapy selectively enhances amyloid beta 1-42 in the
      cerebrospinal fluid of patients with major depression: A prospective pilot study.
AB  - A complex interplay between beta-amyloid (Abeta), Alzheimer's disease (AD) and
      major depression disorder (MDD) suggests that patients with MDD have an altered
      cerebral Abeta metabolism and an increased risk of developing AD. In order to
      elucidate the relationship between antidepressant treatment and Abeta metabolism
      in humans, we performed a study on Abeta peptides in the cerebrospinal fluid
      (CSF) in patients with MDD during electroconvulsive therapy (ECT) as an effective
      antidepressant treatment. We measured the levels of Abeta1-42, Abeta1-40 and of
      tau proteins in the CSF in 12 patients with MDD before and after a course of ECT.
      Abeta1-42 was significantly elevated after the ECT treatment compared to
      baseline, whereas no difference was found for other peptides and proteins such as
      Abeta1-40, Abeta ratio, total tau protein or its phosphorylated form. The most
      salient finding was, that the increase of Abeta1-42 after ECT was found in all
      patients with clinical response to the treatment, but not in those who did not
      respond. The number of ECT sessions of each responding patient correlated with
      the increase of Abeta1-42 in the CSF. Our data point towards to a specific
      antidepressant mechanism which is not based on a general increase of Abeta, but
      seems to involve merely Abeta1-42, the isoform with highest amyloidogenic
      potential. We present the first study in humans demonstrating an isolated
      mobilization of Abeta1-42 in the CSF of patients with depression who respond to
      an ECT treatment.

PMID- 27876184
TI  - Use of Dexmedetomidine to Attenuate Myocardial Injury After Off-Pump Coronary
      Artery Bypass Grafting Surgery.

PMID- 27876185
TI  - Peripheral Near-Infrared Spectroscopy: Methodologic Aspects and a Systematic
      Review in Post-Cardiac Surgical Patients.

PMID- 27876186
TI  - Randomized trial for superiority of high field strength intra-operative magnetic
      resonance imaging guided resection in pituitary surgery.
AB  - Till date there are no randomized trials to suggest the superiority of intra
      operative magnetic resonance imaging (IOMRI) guided trans-sphenoidal pituitary
      resection over two dimensional fluoroscopic (2D-F) guided resections. We
      conducted this trial to establish the superiority of IOMRI in pituitary surgery.
      Primary objective was to compare extent of tumor resection between the two study
      arms. It was a prospective, randomized, outcome assessor and statistician
      blinded, two arm (A: IOMRI, n=25 and B: 2D-F, n=25), parallel group clinical
      trial. 4 patients from IOMRI group cross-over to 2D-F group and were consequently
      analyzed in latter group, based on modified intent to treat method. A total of 50
      patients were enrolled till completion of trial (n=25 in each study arm).
      Demographic profile and baseline parameters were comparable among the two arms
      (p>0.05) except for higher number of endoscopic procedures and experienced
      neurosurgeons (>10years) in arm B (p=0.02, 0.002 respectively). Extent of
      resection was similar in both study arms (A, 94.9% vs B, 93.6%; p=0.78), despite
      adjusting for experience of operating surgeon and use of microscope/endoscope for
      surgical resection. We observed that use of IOMRI helped optimize the extent of
      resection in 5/20 patients (25%) for pituitary tumor resection in-group A.
      Present study failed to observe superiorty of IOMRI over conventional 2D-F guided
      resection in pituitary macroadenoma surgery. By use of this technology, younger
      surgeons could validate their results intra-operatively and hence could increase
      EOR without causing any increase in complications.

PMID- 27876187
TI  - Multiple organ failure by serotype K1 Klebsiella pneumoniae.

PMID- 27876189
TI  - Bacteremia due to Leptotrichia trevisanii after an allogeneic bone marrow
      transplant.

PMID- 27876188
TI  - Infant with exanthema and fever.

PMID- 27876190
TI  - Bilateral abducens nerve palsy as the initial clinical manifestation of
      meningococcal meningitis.

PMID- 27876191
TI  - Breast abscess along with pulmonary mass found in an immunocompetent patient.

PMID- 27876192
TI  - Synthesis and biological evaluation of salinomycin triazole analogues as
      anticancer agents.
AB  - Salinomycin, a polyether antibiotic used for treatment of coccidial disease in
      animal husbandry, has demonstrated promising efficacy for treating different
      cancers. To enrich structure-activity relationship of salinomycin in tumours, we
      prepared a series of new triazole derivatives in specific site of salinomycin by
      click cycloaddition reactions, and assessed their antiproliferative activities on
      breast cancer cell lines. The screening results indicated that most derivatives
      modified at the C20 hydroxyl group have potent antitumour activity. Notably,
      salinomycin triazole dimers were 3.27-4.97 times more toxic than the natural
      substance in ERalpha-positive breast cancer cells (MCF-7), and had moderately
      improved toxicity in triple-negative breast cancer cells (MDA-MB-231).

PMID- 27876193
TI  - Effect of adenovirus-mediated TGF-beta1 gene transfer on the function of rabbit
      articular chondrocytes.
AB  - BACKGROUND: Articular chondrocytes are important in maintaining normal cartilage
      tissue and preventing articular degeneration. Exogenous genes have previously
      been transduced into articular cells using adenoviral vectors to contribute to
      the maintenance of cell function. This study aimed to transfer the transforming
      growth factor-beta1 gene (TGF-beta1) into rabbit articular chondrocytes by
      adenovirus infection to elucidate its effects on cell function. METHODS: Rabbit
      chondrocytes were isolated and cultured both as monolayers and three-dimensional
      culture systems. To achieve overexpression, TGF-beta1 was transfected by
      adenovirus infection, using the LacZ gene as a control. TGF-beta1 protein
      expression was analyzed by western blotting. Quantitative DNA fluorometric
      analysis evaluated cell proliferation, and quantitative reverse transcriptase PCR
      determined the mRNA expression of related chondrocyte marker genes. Western
      blotting and glycosaminoglycan quantitative testing were used to examine changes
      in extracellular matrix components. RESULTS: TGF-beta1 protein expression was
      found to increase in Adv-TGF-beta1-transduced cells, reaching a maximum after
      chondrocytes had been cultured for 4 weeks. Adv-hTGF-beta1 transduction altered
      chondrocyte morphology from fibrocyte-like long spindle-shaped to round or oval.
      TGF-beta1-transduced cells showed an increase in DNA synthesis, glycosaminoglycan
      content, and increased aggrecan and collagen II protein expression, while
      collagen I was significantly decreased. Moreover, TGF-beta1 overexpression
      significantly promoted the mRNA expression of the chondrogenic gene SOX9, and
      inhibited that of the hypertrophic marker COL10A1 and the mineralization marker
      MMP-13. CONCLUSIONS: TGF-beta1 overexpression positively improved the phenotype,
      function, and proliferation of chondrocytes, even after several generations.

PMID- 27876195
TI  - Inclined Wind Tunnel for the Study of Human and Large Animal Flight.

PMID- 27876194
TI  - Predictive factors of overall and major postoperative complications after partial
      nephrectomy: Results from a multicenter prospective study (The RECORd 1 project).
AB  - INTRODUCTION AND OBJECTIVES: To analyze postoperative complications and to assess
      for significant predictive factors during partial nephrectomy (PN) using a large
      multicenter dataset. METHODS: Patients who underwent PN for clinical T1 renal
      tumors at 19 urological Italian centers (Registry of Conservative Renal Surgery
      [RECORd] project) were evaluated between 2009 and 2012. Anthropometric data,
      comorbidities and perioperative outcomes were analyzed. Complications were
      divided as intra- and postoperative, medical and surgical, as appropriate. The
      severity of postoperative complications was graded according to the modified
      Clavien classification system. Patients who experienced intraoperative
      complications were excluded from the analyses for the potential confounding
      effect in the evaluation of predicting factors for postoperative complications.
      RESULTS: Overall, 979 patients were analyzed: open, laparoscopic and robot
      assisted (available since 2011) surgical approaches were used in 522 (56.4%), 286
      (30.9%) and 117 (12.6%) cases, respectively. Surgical postoperative complications
      were reported in 121 (13.1%) cases (32 (3.5%) were Clavien 3), medical were
      reported in 52 (5.6%) cases (3 (0.3%) were Clavien 3). No Clavien 4 complications
      were reported. At multivariable analysis, ECOG score >=1 (OR 1.98; p = 0.002),
      lower preoperative hemoglobin (OR 0.71; p < 0.0001) and open surgical approach
      (2.91; p = 0.02) were significant predictive factors of overall surgical
      postoperative complications, ECOG score >=1 (OR 1.93; p = 0.04) and surgical
      approach (p = 0.05) were significant predictive factors of Clavien 3 either
      surgical or medical postoperative complications. CONCLUSIONS: Comorbidities and
      surgical approach should be considered in preoperative evaluation of patients
      undergoing PN, as they resulted to play a significant role in the occurrence of
      postoperative complications.

PMID- 27876196
TI  - Clinically Significant Envenomation From Postmortem Copperhead (Agkistrodon
      contortrix).
AB  - Over 14,000 copperhead (Agkistrodon contortrix) bites were reported to United
      States poison centers between 1983 and 2008, and 1809 cases were reported to
      poison centers in 2014. The copperhead is primarily found in the southeastern
      United States and belongs to the pit viper subfamily Crotalinae, which also
      includes the water moccasin (Agkistrodon piscivorus) and rattlesnakes (Crotalus
      and Sistrurus genera). Postmortem rattlesnakes have been reported to cause
      clinically significant envenomation; we report a case of a postmortem copperhead
      causing clinically significant envenomation after inadvertent puncture with the
      deceased copperhead fang. The copperhead was transected twice, leaving the snake
      in 3 separate pieces. While handling the snake head, an inadvertent puncture
      occurred on the right index finger followed by pain and swelling in the affected
      extremity necessitating antivenom administration. Care should be taken when
      handling deceased pit vipers due to the continued risk of envenomation.

PMID- 27876197
TI  - Vaccination of special populations: Protecting the vulnerable.
AB  - One of the strategic objectives of the 2011-2020 Global Vaccine Action Plan is
      for the benefits of immunisation to be equitably extended to all people. This
      approach encompasses special groups at increased risk of vaccine-preventable
      diseases, such as preterm infants and pregnant women, as well as those with
      chronic and immune-compromising medical conditions or at increased risk of
      disease due to immunosenescence. Despite demonstrations of effectiveness and
      safety, vaccine uptake in these special groups is frequently lower than expected,
      even in developed countries with vaccination strategies in place. For example,
      uptake of the influenza vaccine in pregnancy rarely exceeds 50% in developed
      countries and, although data are scarce, it appears that only half of preterm
      infants are up-to-date with routine paediatric vaccinations. Many people with
      chronic medical conditions or who are immunocompromised due to disease or aging
      are also under-vaccinated. In the US, coverage among people aged 65years or older
      was 67% for the influenza vaccine in the 2014-2015 season and 55-60% for tetanus
      and pneumococcal vaccines in 2013, while the coverage rate for herpes zoster
      vaccination among those aged 60years or older was only 24%. In most other
      countries, rates are far lower. Reasons for under-vaccination of special groups
      include fear of adverse outcomes or illness caused by the vaccine, the
      inconvenience (and in some settings, cost) of vaccination and lack of awareness
      of the need for vaccination or national recommendations. There is also evidence
      that healthcare providers' attitudes towards vaccination are among the most
      important influences on the decision to vaccinate. It is clear that physicians'
      adherence to recommendations needs to be improved, particularly where patients
      receive care from multiple subspecialists and receive little or no care from
      primary care providers.

PMID- 27876198
TI  - Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test
      negative design.
AB  - BACKGROUND: The test-negative design (TND), an epidemiologic method currently
      used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination
      status of rotavirus-positive cases and rotavirus-negative controls meeting a pre
      defined case definition for acute gastroenteritis. Despite the use of this study
      design in low-income settings, the TND has not been evaluated to measure
      rotavirus vaccine effectiveness. METHODS: This study builds upon prior methods to
      evaluate the use of the TND for influenza vaccine using a randomized controlled
      clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates
      were derived from three large randomized placebo-controlled trials (RCTs) of
      monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa
      and Asia. Derived VE-TND estimates were compared to the original RCT vaccine
      efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus
      vaccine has no effect on rotavirus-negative diarrhea) was also assessed. RESULTS:
      TND vaccine effectiveness estimates were nearly equivalent to original RCT
      vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus
      negative diarrhea. CONCLUSIONS: This study supports the TND as an appropriate
      epidemiologic study design to measure rotavirus vaccine effectiveness in low
      income settings.

PMID- 27876199
TI  - Comparison of homologous and heterologous prime-boost immunizations combining MVA
      vectored and plant-derived VP2 as a strategy against IBDV.
AB  - Different immunogens such as subunit, DNA or live viral-vectored vaccines against
      Infectious Bursal Disease virus (IBDV) have been evaluated in the last years.
      However, the heterologous prime-boost approach using recombinant modified
      vaccinia Ankara virus (rMVA), which has shown promising results in both mammals
      and chickens, has not been tried against this pathogen yet. IBD is a highly
      contagious and immunosuppressive disease of poultry that affects mainly young
      chicks. It is caused by IBDV, a double-stranded RNA virus carrying its main
      antigenic epitopes on the capsid protein VP2. Our objective was to evaluate the
      immune response elicited by two heterologous prime-boost schemes combining an
      rMVA carrying the VP2 mature gene (rVP2) and a recombinant VP2 protein produced
      in Nicotiana benthamiana (pVP2), and to compare them with the performance of the
      homologous pVP2-pVP2 scheme usually used in our laboratory. The SPF chickens
      immunized with the three evaluated schemes elicited significantly higher anti-VP2
      antibody titers (p<0.001) and seroneutralizing titers (p<0.05) and had less T
      cell infiltration (p<0.001), histological damage (p<0.001) and IBDV particles
      (p<0.001) in their bursae of Fabricius when compared with control groups. No
      significant differences were found between both heterologous schemes and the
      homologous one. However, the rVP2-pVP2 scheme showed significantly higher anti
      VP2 antibody titers than pVP2-rVP2 and a similar tendency was found in the
      seroneutralization assay. Conversely, pVP2-rVP2 had the best performance when
      evaluated through bursal parameters despite having a less potent humoral immune
      response. These findings suggest that the order in which rVP2 and pVP2 are
      combined can influence the immune response obtained. Besides, the lack of a
      strong humoral immune response did not lessen the ability to protect from IBDV
      challenge. Therefore, further research is needed to evaluate the mechanisms by
      which these immunogens are working in order to define the combination that
      performs better against IBDV.

PMID- 27876200
TI  - Improving adolescent HPV vaccination in a randomized controlled cluster trial
      using the 4 PillarsTM practice Transformation Program.
AB  - OBJECTIVE: Uptake of meningococcal vaccine (MCV) and tetanus, diphtheria and
      pertussis (Tdap) vaccine among adolescents has approached Healthy People 2020
      goals, but human papillomavirus (HPV) vaccination has not. This study evaluated
      an intervention using the 4 PillarsTM Practice Transformation Program to increase
      HPV, MCV and Tdap uptake among adolescents in primary care practices. METHODS:
      Practices with at least 50 patients 11-17years old with estimated vaccination
      rates less than national goals, were assigned to intervention (n=11) and control
      (n=11) groups in a randomized controlled cluster trial; 9 intervention and 11
      control sites completed the study. The baseline and active study periods were
      7/1/2013-6/30/2014 and 7/1/2014-3/31/2015, respectively. Vaccination and
      demographic data for patients who had a visit in both study periods were derived
      from de-identified EMR extractions. Primary outcomes were vaccination rates and
      percentage point (PP) changes. Data were analyzed in 2015-16. RESULTS: Among the
      cohort of 10,861 adolescent patients, 38% were 11-13years old; 50% were female;
      18% were non-white; and 64% were commercially insured. Average baseline HPV
      initiation rates were 52.5% for intervention and 61.8% for control groups. After
      9months, the intervention sites increased HPV initiation 10.2PP compared with
      7.3PP in control sites (P<0.001); HPV series completion rates did not differ
      between groups. Implementation of >10 strategies to improve rates significantly
      increased the likelihood of HPV series initiation (OR=2.06, 95% CI=1.43, 2.96).
      CONCLUSIONS: Using >10 strategies from the 4 PillarsTM Practice Transformation
      Program is effective for increasing HPV series initiation among adolescents.
      Clinical trial registry number: NCT02165722.

PMID- 27876201
TI  - Changing molecular epidemiology of rotavirus infection after introduction of
      monovalent rotavirus vaccination in Scotland.
AB  - BACKGROUND: Rotaviruses (RV) are the leading cause of gastroenteritis in children
      less than five years of age worldwide. Rotarix(r), a live attenuated monovalent
      vaccine containing a RV strain of G1P[8] specificity has been included in the
      childhood immunisation schedule from June 2013 in Scotland. This study aimed to
      characterise the prevalent RV strains in Scotland before and after the
      introduction of the RV vaccine. METHODS: RV positive faecal samples from Scottish
      virology laboratories covering the years 2012-2015 were genotyped. Viral RNA was
      extracted from faecal suspensions. VP7 and VP4 gene specific primers were used
      for multiplex hemi-nested PCRs and sequencing. Mann-Whitney U test and Chi-square
      test were used for statistical comparison. RESULTS: There was a decrease in RV
      positive samples from the Scottish virology laboratories from 7409 samples in the
      pre-vaccination years (2009-2013) to 760 in 2014-2015, with an annual reduction
      of RV infections by 74.4% (RR-3.95; 95%-CI, 3.53-4.42, p<0.001). 362 samples from
      the pre-vaccination period and 278 samples from the post-vaccination were
      genotyped. There was a drop in prevalence of G1P[8] strains (72.1%, 95%-CI, 67.42
      76.33 to 15%, 95%-CI, 11.38-19.79) after introduction of the vaccine. In the post
      vaccination period G2P[4] was the dominant strain in Scotland (21.9%, 95%-CI,
      17.48-27.17) with increase in G9P[8] (12.9%, 95%-CI, 9.50-7.41), G12P[8] (12.2%,
      95%-CI, 8.89-16.60) and G3P[8] (11.9%, 95%-CI, 8.58-16.20) infections.
      Phylogenetic analysis of the VP7 and VP4 genes showed no major differences
      between the pre and post-vaccination G1P[8] strains. CONCLUSION: This laboratory
      based surveillance study shows significant reduction in reported RV cases and a
      shift in proportion from G1P[8] to G2P[4] strains after introduction of RV
      vaccination in Scotland. The genotyping data from a subset of the total reported
      RV cases will be used to ascertain cross protection against strains and identify
      vaccine induced RV strain shifts in the years to come.

PMID- 27876202
TI  - An interferon inducing porcine reproductive and respiratory syndrome virus
      vaccine candidate elicits protection against challenge with the heterologous
      virulent type 2 strain VR-2385 in pigs.
AB  - Achieving consistent protection by vaccinating pigs against porcine reproductive
      and respiratory syndrome virus (PRRSV) remains difficult. Recently, an interferon
      inducing PRRSV vaccine candidate strain A2MC2 was demonstrated to be attenuated
      and induced neutralizing antibodies. The objective of this study was to determine
      the efficacy of passage 90 of A2MC2 (A2P90) to protect pigs against challenge
      with moderately virulent PRRSV strain VR-2385 (92.3% nucleic acid identity with
      A2MC2) and highly virulent atypical PRRSV MN184 (84.5% nucleic acid identity with
      A2MC2). Forty 3-week old pigs were randomly assigned to five groups including a
      NEG-CONTROL group (non-vaccinated, non-challenged), VAC-VR2385 (vaccinated,
      challenged with strain VR-2385), VR2385 (challenged with strain VR-2385), VAC
      MN184 (vaccinated, challenged with strain MN184) and a MN184 group (challenged
      with MN184 virus). Vaccination was done at 3weeks of age followed by challenge at
      8weeks of age. No viremia was detectable in any of the vaccinated pigs; however,
      by the time of challenge, 15/16 vaccinated pigs had seroconverted based on ELISA
      and had neutralizing antibodies against a homologous strain with titers ranging
      from 8 to 128. Infection with VR-2385 resulted in mild-to-moderate clinical
      disease and lesions. For VR-2385 infected pigs, vaccination significantly lowered
      PRRSV viremia and nasal shedding by 9days post challenge (dpc), significantly
      reduced macroscopic lung lesions, and significantly increased the average daily
      weight gain compared to the non-vaccinated pigs. Infection with MN184 resulted in
      moderate-to-severe clinical disease and lesions regardless of vaccination status;
      however, vaccinated pigs had significantly less nasal shedding by dpc 5 compared
      to non-vaccinated pigs. Under the study conditions, the A2P90 vaccine strain was
      attenuated without detectable shedding, improved weight gain, and offered
      protection to the pigs challenged with VR-2385 by reduction of virus load and
      macroscopic lung lesions. Further work is needed to investigate different
      vaccination and challenge protocols, including routes, doses, timing and strains.

PMID- 27876204
TI  - Distinct functions of human RecQ helicases during DNA replication.
AB  - DNA replication is the most vulnerable process of DNA metabolism in proliferating
      cells and therefore it is tightly controlled and coordinated with processes that
      maintain genomic stability. Human RecQ helicases are among the most important
      factors involved in the maintenance of replication fork integrity, especially
      under conditions of replication stress. RecQ helicases promote recovery of
      replication forks being stalled due to different replication roadblocks of either
      exogenous or endogenous source. They prevent generation of aberrant replication
      fork structures and replication fork collapse, and are involved in proper
      checkpoint signaling. The essential role of human RecQ helicases in the genome
      maintenance during DNA replication is underlined by association of defects in
      their function with cancer predisposition.

PMID- 27876205
TI  - Activating Patients.

PMID- 27876203
TI  - Impact of the national targeted Hepatitis A immunisation program in Australia:
      2000-2014.
AB  - In November 2005, hepatitis A vaccine was funded under the Australian National
      Immunisation Program for Aboriginal and Torres Strait Islander (Indigenous)
      children aged 12-24months in the targeted jurisdictions of Queensland, South
      Australia, Western Australia and the Northern Territory. We reviewed the
      epidemiology of hepatitis A from 2000 to 2014 using data from the Australian
      National Notifiable Diseases Surveillance System, the National Hospital Morbidity
      Database, and Australian Bureau of Statistics causes-of-death data. The impact of
      the national hepatitis A immunisation program was assessed by comparison of pre
      vaccine (2000-2005) and post-vaccine time periods (2006-2014), by age group,
      Indigenous status and jurisdiction using incidence rate ratios (IRR) per 100,000
      population and 95% confidence intervals (CI). The national pre-vaccine
      notification rate in Indigenous people was four times higher than the non
      Indigenous rate, and declined from 8.41 per 100,000 (95% CI 5.03-11.79) pre
      vaccine to 0.85 per 100,000 (95% CI 0.00-1.99) post-vaccine, becoming similar to
      the non-Indigenous rate. Notification and hospitalisation rates in Indigenous
      children aged <5years from targeted jurisdictions declined in the post-vaccine
      period when compared to the pre-vaccine period (notifications: IRR=0.07; 95% CI
      0.04-0.13; hospitalisations: IRR=0.04; 95% CI 0.01-0.16). As did notification
      rates in Indigenous people aged 5-19 (IRR=0.08; 95% CI 0.05-0.13) and 20-49years
      (IRR=0.06; 95% CI 0.02-0.15) in targeted jurisdictions. For non-Indigenous people
      from targeted jurisdictions, notification rates decreased significantly in
      children aged <5years (IRR 0.47; 95% CI 0.31-0.71), and significantly more
      overall (IRR=0.43; 95% CI 0.39-0.47) compared to non-Indigenous people from non
      targeted jurisdictions (IRR=0.60; 95% CI 0.56-0.64). The national hepatitis A
      immunisation program has had a significant impact in the targeted population with
      relatively modest vaccine coverage, with evidence suggestive of substantial herd
      protection effects.

PMID- 27876206
TI  - Synergistic anti-cancer effects of galangin and berberine through apoptosis
      induction and proliferation inhibition in oesophageal carcinoma cells.
AB  - Galangin is an active pharmacological ingredient from propolis and Alpinia
      officinarum Hance, and has been reported to have anti-cancer and antioxidative
      properties. Berberine, a major component of Berberis vulgaris extract, exhibits
      potent anti-cancer activities through distinct molecular mechanisms. However, the
      anticancer effect of galangin in combination with berberine is still unknown. In
      the present study, we demonstrated that the combination of galangin with
      berberine synergistically resulted in cell growth inhibition, apoptosis and cell
      cycle arrest at G2/M phase with the increased intracellular reactive oxygen
      species (ROS) levels in oesophageal carcinoma cells. Pretreatment with ROS
      scavenger promoted the apoptosis dramatically induced by co-treatment with
      galangin and berberine. Treatment with galangin and berberine alone caused the
      decreased expressions of Wnt3a and beta-catenin. Interestingly, combination of
      galangin with berberine could further suppress Wnt3a and beta-catenin expression
      and induce apoptosis in cancer cells. Additionally, in nude mice with xenograft
      tumors, the combinational treatment of galangin and berberine significantly
      inhibited the tumor growth without obvious toxicity. Overall, galangin in
      combination with berberine presented outstanding synergistic anticancer role in
      vitro and in vivo, indicating that the beneficial combination of galangin and
      berberine might provide a promising treatment for patients with oesophageal
      carcinoma.

PMID- 27876207
TI  - Aglycone rich extracts of phytoestrogens cause ROS-mediated DNA damage in breast
      carcinoma cells.
AB  - Phytoestrogens are known for their physiological role in lowering risk of
      osteoporosis, heart disease, breast cancer and menopausal symptoms. They are
      plant derived potent anti-oxidants, but tend to show pro-oxidant effect at higher
      concentrations. This study has been undertaken to exploit their pro-oxidant
      effect in the management of cancer. Cancer cells inherently possess high
      intracellular ROS levels, however, these levels do not cause harm to the cancer
      cells because of the anti-oxidant enzyme system. So, there is a need for a
      treatment strategy which could modulate the ROS levels. Breast cancer cell lines
      MCF-7 and MDA-MB-231 are treated with various concentrations of soyabean aglycone
      rich extracts (SARE) and flaxseed aglycone rich extracts (FSARE). The treatment
      brings about a significant decrease in super oxide dismutase (SOD) and
      glutathione peroxidase (GPx) activity, thereby leading to accumulation of
      superoxide ion and peroxide in the cells. The catalase (CAT) activity however,
      did not show a dose dependent change. The intra-cellular reactive oxygen species
      (ROS) levels increased and a marked change in mitochondrial membrane potential
      was detected. Cell cycle arrest was seen at S and G2/M phase in MCF-7 cells and
      high accumulation of cells in Sub G1 phase was seen in MDA-MB-231 cells.
      Microscopic evaluation indicated apoptotic morphology and DNA damage. This study
      suggests an important role of soyabean and flaxseed aglycones in modulating
      intracellular ROS in breast carcinoma.

PMID- 27876208
TI  - Betulinic acid protects against cerebral ischemia/reperfusion injury by
      activating the PI3K/Akt signaling pathway.
AB  - Betulinic acid (BA), a naturally occurring pentacyclic lupane group triterpenoid,
      has been demonstrated to protect against ischemia/reperfusion-induced renal
      damage. However, the effects of BA on cerebral ischemia/reperfusion (I/R) injury
      remain unclear. Hence, this study was to investigate the effects of BA on oxygen
      and glucose deprivation/reperfusion (OGD/R) induced neuronal injury in rat
      hippocampal neurons. Our results showed that BA pretreatment greatly attenuated
      OGD/R-induced neuronal injury. BA also inhibited OGD/R-induced intracellular ROS
      production and MDA level in rat hippocampal neurons. Furthermore, the down
      regulation of Bcl-2, up-regulation of Bax and the consequent activation of
      caspase-3 induced by OGD/R were reversed by BA pretreatment. Mechanistic studies
      demonstrated that BA pretreatment up-regulated the expression levels of p-PI3K
      and p-Akt in hippocampal neurons induced by OGD/R. Taken together, these data
      suggested that BA inhibits OGD/R-induced neuronal injury in rat hippocampal
      neurons through the activation of PI3K/Akt signaling pathway.

PMID- 27876209
TI  - Synthesis and biological evaluation against Mycobacterium tuberculosis and
      Leishmania amazonensis of a series of diaminated terpenoids.
AB  - We report the synthesis of a series of diaminated terpenoids containing, as side
      chain of the diamine core, the "head-to-tail" prenyl derivatives, with amino
      amino spacers of variable length. In vitro biological activity of these compounds
      was evaluated against Mycobacterium tuberculosis and Leishmania amazonensis, and
      the structure-activity relationships are discussed. Different biological results
      were observed depending on the terpenic side-chain length. The best results were
      obtained for trans,trans-farnesol derivatives. Moreover, these results
      demonstrated that the stereochemistry of the double bond could play an important
      role in determining antitubercular and antileishmanial activities of these
      compounds.

PMID- 27876210
TI  - Conditioned medium from LS 174T goblet cells treated with oxyresveratrol
      strengthens tight junctions in Caco-2 cells.
AB  - BACKGROUND: Strengthening of intestinal tight junctions provides an effective
      barrier from the external environment. Goblet cell-derived trefoil factor 3
      (TFF3) increases transepithelial resistance by upregulating the expression of
      tight junction proteins. Oxyresveratrol (OXY) is a hydroxyl-substituted stilbene
      found in the roots, leaves, stems, and fruit of many plants and known to have
      various biological activities. In this study, we investigated the strengthening
      effect of OXY on intestinal tight junctions through stimulation of TFF production
      in goblet cells. METHODS: We prepared conditioned medium from LS 174T goblet
      cells treated with OXY (GCO-CM) and investigated the effect of GCO-CM on
      strengthening tight junctions of Caco-2 cells. The mRNA and protein expression
      levels of major tight junction components (claudin-1, occludin, and ZO-1) were
      measured by quantitative real-time PCR and western blotting, respectively.
      Transepithelial electric resistance (TEER) was measured using an ohm/V meter.
      Monolayer permeability was evaluated by paracellular transport of fluorescein
      isothiocyanate-dextran. RESULTS: OXY showed a strong antioxidant activity. It
      significantly increased the expression level of TFF3 in LS 174T goblet cells. GCO
      CM prepared by treatment with 2.5, 5, and 10MUg/ml OXY did not show cytotoxicity
      in Caco-2 cells. GCO-CM increased the mRNA and protein expression levels of
      claudin-1, occludin, and ZO-1. It also significantly increased tight junction
      integrity and reduced permeability in a dose-dependent manner. CONCLUSION: OXY
      stimulates the expression of TFF3 in goblet cells, which might increase the
      integrity of the intestinal tight junction barrier.

PMID- 27876211
TI  - Evaluation of anti-proliferative and anti-inflammatory activities of Pelagia
      noctiluca venom in Lipopolysaccharide/Interferon-gamma stimulated RAW264.7
      macrophages.
AB  - Components of Pelagia noctiluca (P. noctiluca) venom were evaluated for their
      anticancer and nitric Oxide (NO) inhibition activities. Three fractions, out of
      four, obtained by gel filtration on Sephadex G75 of P. noctiluca venom revealed
      an important selective anti-proliferative activity on several cell lines such as
      human bladder carcinoma (RT112), human glioblastoma (U87), and human myelogenous
      leukemia (K562) but not on mitogen-stimulated peripheral blood mononuclear cells.
      Interestingly, P. noctiluca components showed an important dose-dependent anti
      inflammatory activity, through inhibition of NO production via transcriptional
      regulation of Inducible NO Synthase (iNOS), in IFN-gamma/LPS stimulated RAW 264.7
      macrophages. These data strongly suggest that P. noctiluca venom could be used as
      a natural inhibitor of cancer cell lines and a potent anti-inflammatory agent for
      the treatment of anti-inflammatory diseases.

PMID- 27876212
TI  - Alteration in Oxidative/nitrosative imbalance, histochemical expression of
      osteopontin and antiurolithiatic efficacy of Xanthium strumarium (L.) in ethylene
      glycol induced urolithiasis.
AB  - Xanthium strumarium has traditionally been used in the treatment of urolitiasis
      especially by the rural people in India, but its antiurolithiatic efficacy was
      not explored scientifically till now. Therefore, the present study was designed
      to validate the ethnic practice scientifically, and explore the possible
      antiurolithiatic effect to rationalize its medicinal use. Urolitiasis was induced
      in hyperoxaluric rat model by giving 0.75% ethylene glycol (EG) for 28days along
      with 1% ammonium chloride (AC) for first 14days. Antiurolithiatic effect of
      aqueous-ethanol extract of Xanthium strumarium bur (xanthium) was evaluated based
      on urine and serum biochemistry, oxidative/nitrosative stress indices,
      histopathology, kidney calcium and calcium oxalate content and
      immunohistochemical expression of matrix glycoprotein, osteopontin (OPN).
      Administration of EG and AC resulted in hyperoxaluria, crystalluria,
      hypocalciuria, polyurea, raised serum urea, creatinine, erythrocytic lipid
      peroxidise and nitric oxide, kidney calcium content as well as crystal deposition
      in kidney section in lithiatic group rats. However, xanthium treatment
      significantly restored the impairment in above kidney function test as that of
      standard treatment, cystone. The up-regulation of OPN was also significantly
      decreased after xanthium treatment. The present findings demonstrate the curative
      efficacy of xanthium in ethylene glycol induced urolithiasis, possibly mediated
      through inhibition of various pathways involved in renal calcium oxalate
      formation, antioxidant property and down regulation of matrix glycoprotein, OPN.
      Therefore, future studies may be established to evaluate its efficacy and safety
      for clinical use.

PMID- 27876213
TI  - The impact of methotrexate on lung inflammatory and apoptotic pathway biomarkers
      The role of gallic acid.
AB  - BACKGROUNDS: The aim of this study was to investigate the effects of methotrexate
      (MTX) on the lung via inflammatory and apoptotic pathway biomarkers and the role
      of gallic acid (GA). METHODS: In this study, twenty four male Wistar-Albino rats
      weighing 300-350g were divided into 3 groups as follows; Control group
      (0.1ml/oral saline, for 7 days+2nd day i.p.). MTX group (20mg/kg, single dose, on
      2nd day). MTX+GA group (15mg/kg, orally, for 7 days). Comet analysis, oxidant
      antioxidant status, IMA were conducted. Histopathological analyses were
      evaluated. RESULTS: Comet assay on the blood, TOS and OSI values in the lung were
      increased in the group II compared with the control group (p<0.05). GA
      significantly reduced the comet score and IMA levels in the blood, TOS and OSI
      values in the lung tissue in group III compared with group II (p<0.05).
      Immunohistochemically PGE2, TNF-alpha, CRP, serum SAA, Caspase 3 and Caspase 9
      expressions significantly increased in group II compared with the control group
      (p<0.001) and GA treatment ameliorated these parameters significantly in group
      III compared with group II (p<0.001). CONCLUSIONS: MTX caused oxidative stress
      and DNA damage in the blood tissue and caused oxidative damage, inflammation and
      apoptosis in the lung tissue.

PMID- 27876214
TI  - Beneficial effects of Plantago albicans on high-fat diet-induced obesity in rats.
AB  - Obesity is a one of the main global public health problems associated with
      chronic diseases such as coronary heart disease, diabetes and cancer. As a
      solution to obesity, we suggest Plantago albicans, which is a medicinal plant
      with several biological effects. This study assesses the possible anti-obesity
      protective properties of Plantago albicans in high fat diet-fed rats. 28 male
      Wistar rats were divided into 4 groups; a group which received normal diet (C),
      the second group was fed HDF diet (HDF), the third group was given normal diet
      supplemented with Plantago albicans (P.AL), and the fourth group received HDF
      supplemented with Plantago albicans (HDF+P.AL) (30mg/kg/day) for 7 weeks. Our
      results showed an increase in body weight of HDF rats by ~16% as compared to the
      control group with an increase in the levels of total cholesterol (TC) as well as
      LDL-cholesterol, triglycerides (TG) in serum. Also, the concentration of TBARS
      increased in the liver and heart of HDF-fed rats as compared to the control
      group. The oral gavage of Plantago albicans extract to obese rats induced a
      reduction in their body weight, lipid accumulation in liver and heart tissue,
      compared to the high-fat diet control rats. The obtained results proved that the
      antioxidant potency of Plantago albicans extracts was correlated with their
      phenolic and flavonoid contents. The antioxidant capacity of the extract was
      evaluated by DPPH test (as EC50=250+/-2.12MUg/mL) and FRAP tests (as EC50=27.77+/
      0.14MUg/mL). These results confirm the phytochemical and antioxidant impact of
      Plantago albicans extracts. Plantago albicans content was determined using
      validated HPLC methodology.

PMID- 27876215
TI  - Serological evaluation of ovarian steroids of red-rumped agouti (Dasyprocta
      leporina) during the estrous cycle phases.
AB  - The objective of this study was to evaluate serum progesterone (P4) and 17beta
      estradiol (E2) concentrations throughout the estrous cycle in the red-rumped
      agouti (Dasyprocta leporina). A total of eight multiparous, captive-bred females
      were bled throughout their estrous cycle via saphenous venipuncture, with E2 and
      P4 concentrations being measured via ELISA of the serum collected. Serum E2
      ranged from 1212 to 3500pg/ml with a peak value coinciding with observed estrus.
      However, two additional peak values for E2 were also recorded, one each in
      metestrus and proestrus respectively. P4 concentrations reached a maximum of
      4.23ng/ml, and increases in P4 immediately followed the second E2 peak in
      metestrus. The highest concentrations of P4 were recorded in mid diestrus;
      between days 23-25 of the 31-day cycle. This phase was the longest in the agouti,
      consisting of approximately 19days and accounted for 61% of the cycle. This study
      increased the basal scientific reproductive knowledge of this potentially
      valuable neo-tropical species.

PMID- 27876216
TI  - Corrigendum to "Structural elucidation and evaluation of multidrug-resistance
      modulatory capability of Amarissinins A-C, diterpenes derived from Salvia
      amarissima" [Fitoterapia 114 (2016) 1-6].

PMID- 27876217
TI  - Spontaneous Pneumothorax Complicating Miliary Tuberculosis.

PMID- 27876219
TI  - Optimizing the outcome of transnasal endoscopic sphenopalatine artery ligation in
      managing refractory posterior epistaxis: A case-control analysis.
AB  - OBJECTIVE: To optimize the outcome of transnasal endoscopic sphenopalatine artery
      ligation (TESPAL) by determining the key surgical steps and applying them
      accordingly. METHODS: This is a case-control study carried out in a tertiary care
      teaching institution on subjects who underwent TESPAL during the period of
      October 2010 to September 2015. Their surgical and clinical records were
      reviewed, and success (no re-bleed) and failure (return with re-bleed) were
      considered the main outcome measures of TESPAL. Accordingly, depending on whether
      the subjects returned with re-bleed or not, they were classified as "failure" and
      "success" groups. After appropriate matching in terms of age, gender and a given
      set of exclusion criteria that could influence per-operative decision-making or
      contribute to post-operative epistaxis, the groups were considered as cases
      (subjects undergoing TESPAL and returned with re-bleed; part of the "failure"
      group following matching) and controls (subjects undergoing TESPAL and did not
      return with re-bleed; part of the "success" group following matching). Per
      operative/surgical factors executed or followed in varied combinations in each
      group that influenced the outcome of TESPAL were then identified from the
      surgical notes and were subsequently analyzed statistically. RESULTS: In 89% of
      cases, the sphenopalatine artery (SPA) pedicle was either clipped or cauterized,
      whereas in 90% of the controls, it was both clipped and cauterized. The posterior
      nasal artery (PNA), when found, was cauterized in 25% of the cases, compared to
      85% in the controls. Also, the septal artery region was cauterized in only 33% of
      cases. Both cauterization/clipping of the SPA along with cauterization of PNA was
      done in 69% of the controls, whereas in 59% the septal artery region was also
      cauterized. However, there were no cases when all these steps were combined. The
      results were statistically significant. CONCLUSION: When only the per
      operative/surgical factors were considered, the outcome of TESPAL was most
      favorable when the procedure could be done combining both clipping and
      cauterization of the SPA, along with cauterization of the PNA and the septal
      artery region.

PMID- 27876218
TI  - Antifungal activities of selected essential oils against Fusarium oxysporum f.
      sp. lycopersici 1322, with emphasis on Syzygium aromaticum essential oil.
AB  - The antifungal effects of four essential oils viz., clove (Syzygium aromaticum),
      lemongrass (Cymbopogon citratus), mint (Mentha * piperita) and eucalyptus
      (Eucalyptus globulus) were evaluated against wilt causing fungus, Fusarium
      oxysporum f. sp. lycopersici 1322. The inhibitory effect of oils showed dose
      dependent activity on the tested fungus. Most active being the clove oil,
      exhibiting complete inhibition of mycelial growth and spore germination at 125
      ppm with IC50 value of 18.2 and 0.3 ppm, respectively. Essential oils of
      lemongrass, mint and eucalyptus were inhibitory at relatively higher
      concentrations. The Minimum inhibitory concentration (MIC) of clove oil was 31.25
      ppm by broth microdilution method. Thirty one different compounds of clove oil,
      constituting approximately >=99% of the oil, were identified by gas
      chromatography-mass spectroscopy analysis. The major components were eugenol
      (75.41%), E-caryophyllene (15.11%), alpha-humulene (3.78%) and caryophyllene
      oxide (1.13%). Effect of clove oil on surface morphology of F. oxysporum f. sp.
      lycopersici 1322 was studied by scanning electron microscopy (SEM) and atomic
      force microscopy (AFM). SEM observation revealed shrivelled hyphae while AFM
      observation showed shrunken and disrupted spores in clove oil treated samples. In
      pots, 5% aqueous emulsion of clove oil controlled F. oxysporum f. sp. lycopersici
      1322 infection on tomato plants. This study demonstrated clove oil as potent
      antifungal agent that could be used as biofungicide for the control of F.
      oxysporum f. sp. lycopersici in both preventive and therapeutic manner.

PMID- 27876220
TI  - Breaking bad news to patients with cancer: A randomized control trial of a brief
      communication skills training module incorporating the stories and preferences of
      actual patients.
AB  - OBJECTIVE: This study tested the effectiveness of a brief, learner-centered,
      breaking bad news (BBN) communication skills training module using objective
      evaluation measures. METHODS: This randomized control study (N=66) compared
      intervention and control groups of students (n=28) and residents' (n=38)
      objective structured clinical examination (OSCE) performance of communication
      skills using Common Ground Assessment and Breaking Bad News measures. RESULTS:
      Follow-up performance scores of intervention group students improved
      significantly regarding BBN (colon cancer (CC), p=0.007, r=-0.47; breast cancer
      (BC), p=0.003, r=-0.53), attention to patient responses after BBN (CC, p<0.001,
      r=-0.74; BC, p=0.001, r=-0.65), and addressing feelings (BC, p=0.006, r=-0.48).
      At CC follow-up assessment, performance scores of intervention group residents
      improved significantly regarding BBN (p=0.004, r=-0.43), communication related to
      emotions (p=0.034, r=-0.30), determining patient's readiness to proceed after BBN
      and communication preferences (p=0.041, r=-0.28), active listening (p=0.011, r=
      0.37), addressing feelings (p<0.001, r=-0.65), and global interview performance
      (p=0.001, r=-0.51). CONCLUSION: This brief BBN training module is an effective
      method of improving BBN communication skills among medical students and
      residents. PRACTICE IMPLICATIONS: Implementation of this brief individualized
      training module within health education programs could lead to improved
      communication skills and patient care.

PMID- 27876221
TI  - Effectiveness of an internet-based education on maternal satisfaction in NICUs.
AB  - OBJECTIVE: This study was conducted to evaluate the effect of internet-based
      education on the satisfaction of the mothers of the preterm neonates in the
      NICUs. METHODS: This quasi-experimental study was conducted on 80 mothers of
      preterm neonates hospitalized in the NICUs of two hospitals in Iran during 9
      months. The mothers were assigned in two groups as cases and controls. The
      satisfaction level of the mothers was evaluated by using WBPL-Revised1 in both
      groups on the first and tenth day of the study. Mothers in the case group
      received the educational program available at www.iranlms.ir/myinfant for 10days.
      After 10days, the satisfaction level of the mothers in both groups was measured
      by questionnaire again. RESULT: the satisfaction of the mothers increased in both
      groups after this intervention. However, comparison of the mean scores revealed
      that the satisfaction of the mothers in the case group increased significantly
      following the intervention (P<0.001). CONCLUSION: Considering the benefits of
      internet-based education, its utilization in mothers education programs in NICUs
      is recommended. PRACTICE IMPLICATIONS: The results of this study show nurses in
      the NICU is a way to improve communication and education to parents of infants
      hospitalized in NICU.

PMID- 27876223
TI  - Monitoring of organochlorine pesticides in blood of women with uterine cervix
      cancer.
AB  - In Yucatan, Mexico, chronic exposure of Mayan population to pesticides is
      expected as about 30 per cent are drinking polluted water. Residues of
      organochlorine pesticides (OCP) were monitored in 18 municipalities of Yucatan
      with high mortality rates due to uterine cervix cancer. 70 blood samples
      collected from Mayan women living in livestock, agricultural and metropolitan
      area were analyzed for OCP. Solid Phase Extraction was performed on C18
      cartridges and analyzed by Gas Chromatography with Electron Capture Detector. The
      results showed that the highest OCP levels were detected in blood of women living
      in the livestock area. OCP detected were endosulfan I (7.35 MUg/mL), aldrin (3.69
      MUg/mL), 4,4' DDD (2.33 MUg/mL), 1.39 and 1.46 MUg/mL of delta-HCH. Women from
      the agricultural area had high concentrations of OCP in their blood, particularly
      dieldrin (1.19 MUg/mL), and 1.26 MUg/mL of 4,4' DDE. In the metropolitan area,
      0.080 MUg/mL of gamma-HCH and 0.064 MUg/mL of heptachlore were detected. This
      monitoring study was also based on epidemiological data of uterine cervical
      cancer. It was found that environmental factors may have facilitated the
      infiltration of OCP to the aquifer used for potable water supply. These factors
      in addition to poverty can have impacts on public health. This first exploratory
      study suggests that monitoring of OCP in human is important for the establishment
      of health promotion programs. The integrative analysis of both, environmental and
      social factors would be helpful to characterize the bioaccumulation of pesticides
      in humans.

PMID- 27876222
TI  - Environmental exposure to TiO2 nanomaterials incorporated in building material.
AB  - Nanomaterials are increasingly being used to improve the properties and functions
      of common building materials. A new type of self-cleaning cement incorporating
      TiO2 nanomaterials (TiO2-NMs) with photocatalytic properties is now marketed.
      This promising cement might provide air pollution-reducing properties but its
      environmental impact must be validated. During cement use and aging, an altered
      surface layer is formed that exhibits increased porosity. The surface layer
      thickness alteration and porosity increase with the cement degradation rate. The
      hardened cement paste leaching behavior has been fully documented, but the fate
      of incorporated TiO2-NMs and their state during/after potential release is
      currently unknown. In this study, photocatalytic cement pastes with increasing
      initial porosity were leached at a lab-scale to produce a range of degradation
      rates concerning the altered layer porosity and thickness. No dissolved Ti was
      released during leaching, only particulate TiO2-NM release was detected. The
      extent of release from this batch test simulating accelerated worst-case scenario
      was limited and ranged from 18.7 +/- 2.1 to 33.5 +/- 5.1 mg of Ti/m2 of cement
      after 168 h of leaching. TiO2-NMs released into neutral aquatic media (simulate
      pH of surface water) were not associated or coated by cement minerals. The TiO2
      NM release mechanism is suspected to start from freeing of TiO2-NMs in the
      altered layer pore network due to partial cement paste dissolution followed by
      diffusion into the bulk pore solution to the surface. The extent of TiO2-NM
      release was not solely related to the cement degradation rate.

PMID- 27876224
TI  - Microenvironmental air quality impact of a commercial-scale biomass heating
      system.
AB  - Initiatives to displace petroleum and climate change mitigation have driven a
      recent increase in space heating with biomass combustion. However, there is ample
      evidence that biomass combustion emits significant quantities of health damaging
      pollutants. We investigated the near-source micro-environmental air quality
      impact of a biomass-fueled combined heat and power system equipped with an
      electrostatic precipitator (ESP) in Syracuse, NY. Two rooftop sampling stations
      with PM2.5 and CO2 analyzers were established in such that one could capture the
      plume while the other one served as the background for comparison depending on
      the wind direction. Four sonic anemometers were deployed around the stack to
      quantify spatially and temporally resolved local wind patterns. Fuel-based
      emission factors were derived based on near-source measurement. The Comprehensive
      Turbulent Aerosol Dynamics and Gas Chemistry (CTAG) model was then applied to
      simulate the spatial variations of primary PM2.5 without ESP. Our analysis shows
      that the absence of ESP could lead to an almost 7 times increase in near-source
      primary PM2.5 concentrations with a maximum concentration above 100 MUg m-3 at
      the building rooftop. The above-ground "hotspots" would pose potential health
      risks to building occupants since particles could penetrate indoors via
      infiltration, natural ventilation, and fresh air intakes on the rooftop of
      multiple buildings. Our results demonstrated the importance of emission control
      for biomass combustion systems in urban area, and the need to take above-ground
      pollutant "hotspots" into account when permitting distributed generation. The
      effects of ambient wind speed and stack temperature, the suitability of airport
      meteorological data on micro-environmental air quality were explored, and the
      implications on mitigating near-source air pollution were discussed.

PMID- 27876225
TI  - Glyphosate and AMPA distribution in wind-eroded sediment derived from loess soil.
AB  - Glyphosate is one of the most used herbicides in agricultural lands worldwide.
      Wind-eroded sediment and dust, as an environmental transport pathway of
      glyphosate and of its main metabolite aminomethylphosphonic acid (AMPA), can
      result in environmental- and human exposure far beyond the agricultural areas
      where it has been applied. Therefore, special attention is required to the
      airborne transport of glyphosate and AMPA. In this study, we investigated the
      behavior of glyphosate and AMPA in wind-eroded sediment by measuring their
      content in different size fractions (median diameters between 715 and 8 MUm) of a
      loess soil, during a period of 28 days after glyphosate application.
      Granulometrical extraction was done using a wind tunnel and a Soil Fine Particle
      Extractor. Extractions were conducted on days 0, 3, 7, 14, 21 and 28 after
      glyphosate application. Results indicated that glyphosate and AMPA contents were
      significantly higher in the finest particle fractions (median diameters between 8
      and 18 MUm), and lowered significantly with the increase in particle size.
      However, their content remained constant when aggregates were present in the
      sample. Glyphosate and AMPA contents correlated positively with clay, organic
      matter, and silt content. The dissipation of glyphosate over time was very low,
      which was most probably due to the low soil moisture content of the sediment.
      Consequently, the formation of AMPA was also very low. The low dissipation of
      glyphosate in our study indicates that the risk of glyphosate transport in dry
      sediment to off-target areas by wind can be very high. The highest glyphosate and
      AMPA contents were found in the smallest soil fractions (PM10 and less), which
      are easily inhaled and, therefore, contribute to human exposure.

PMID- 27876226
TI  - Effect of the selective pressure of sub-lethal level of heavy metals on the fate
      and distribution of ARGs in the catchment scale.
AB  - Our previous study demonstrated that high levels of antibiotic resistance genes
      (ARGs) in the Haihe River were directly attributed to the excessive use of
      antibiotics in animal agriculture. The antibiotic residues of the Xiangjiang
      River determined in this study were much lower than those of the Haihe River, but
      the relative abundance of 16 detected ARGs (sul1, sul2 and sul3, qepA, qnrA,
      qnrB, qnrD and qnrS, tetA, tetB, tetW, tetM, tetQ and tetO, ermB and ermC), were
      as high as the Haihe River particularly in the downstream of the Xiangjiang River
      which is close to the extensive metal mining. The ARGs discharged from the
      pharmaceutical wastewater treatment plant (PWWTP) are a major source of ARGs in
      the upstream of the Xiangjiang River. In the downstream, selective stress of
      heavy metals rather than source release had a significant influence on the
      distinct distribution pattern of ARGs. Some heavy metals showed a positive
      correlation with certain ARG subtypes. Additionally, there is a positive
      correlation between individual ARG subtypes and heavy metal resistance genes,
      suggesting that heavy metals may co select the ARGs on the same plasmid of
      antibiotic resistant bacteria. The co-selection mechanism between specific metal
      and antibiotic resistance was further confirmed by these isolations encoding the
      resistance genotypes to antibiotics and metals. To our knowledge, this is the
      first study on the fate and distribution of ARGs under the selective pressure
      exerted by heavy metals in the catchment scale. These results are beneficial to
      understand the fate, and to discern the contributors of ARGs from either the
      source release or the selective pressure by sub-lethal levels of environmental
      stressors during their transport on a river catchment scale.

PMID- 27876228
TI  - Toxic effects of microplastic on marine microalgae Skeletonema costatum:
      Interactions between microplastic and algae.
AB  - To investigate toxic effects of microplastic on marine microalgae Skeletonema
      costatum, both algal growth inhibition test and non-contact shading test were
      carried out, and algal photosynthesis parameters were also determined. The SEM
      images were used to observe interactions between microplastic and algae. It was
      found that microplastic (mPVC, average diameter 1 MUm) had obvious inhibition on
      growth of microalgae and the maximum growth inhibition ratio (IR) reached up to
      39.7% after 96 h exposure. However, plastic debris (bPVC, average diameter 1 mm)
      had no effects on growth of microalgae. High concentration (50 mg/L) mPVC also
      had negative effects on algal photosynthesis since both chlorophyll content and
      photosynthetic efficiency (PhiPSII) decreased under mPVC treatments. Shading
      effect was not one reason for toxicity of microplastic on algae in this study.
      Compared with non-contact shading effect, interactions between microplastic and
      microalage such as adsorption and aggregation were more reasonable explanations
      for toxic effects of microplastic on marine microalgae. The SEM images provided a
      more direct and reasonable method to observe the behaviors of microplastic.

PMID- 27876227
TI  - Phthalate levels and related factors in children aged 6-12 years.
AB  - Although previous studies showed that children are widely exposed to phthalates,
      the sources of phthalate exposure for school-aged children in China are not well
      understood. This study aimed to assess phthalate metabolite levels and explore
      the factors influencing exposure in children. We collected demographic data and
      biological samples from 336 children aged 6-12 years. We calculated urinary
      concentrations of 14 mono-phthalate metabolites and conducted chi-square (chi2)
      tests and logistic regression analysis to determine the variables associated with
      phthalate levels. Mono-n-butyl phthalate (MnBP) and mono-(2-ethyl-5-hydroxyhexyl)
      phthalate (MEHHP) were the most abundant urinary phthalate metabolites. In
      addition, housing type, decorating materials in the home, and frequency of canned
      food consumption were associated with exposure to low molecular weight
      phthalates. Water source, duration of time spent playing with toys, residential
      area, and frequency of canned food consumption were associated with exposure to
      high molecular weight phthalates. Based on these results, potential strategies to
      reduce exposure to phthalates include avoiding plastic food containers and
      chemical fragrances as well as eating fewer processed foods, especially canned
      foods, and foods in plastic packaging.

PMID- 27876229
TI  - Temporal trends of chlorinated paraffins and polychlorinated biphenyls in Swiss
      soils.
AB  - Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs),
      are ubiquitous environmental contaminants that have been targeted by national
      regulations since the 1970-1980s, followed in 2004 by the worldwide regulation
      under the Stockholm Convention on POPs. However, concerns are growing regarding
      the emergence of additional POP-like substances, such as chlorinated paraffins
      (CPs), which have particularly large production volumes. Whereas short-chain CPs
      (SCCPs) have recently been restricted in Europe and are currently under
      evaluation for inclusion into the Stockholm Convention, medium-chain CPs (MCCPs)
      have received little attention. On the one hand, temporal trends of CPs in the
      environment have hardly been investigated. On the other hand, the effectiveness
      of the Stockholm Convention on environmental levels of PCBs is still a matter of
      debate. Here, we reconstructed temporal trends of SCCPs, MCCPs, and PCBs in
      archived soil samples from six sampling sites in Switzerland, covering the period
      1989-2014 (respectively 1988-2013 for one site). Concentrations of SCCPs have
      decreased in soil since 1994, which indicates positive effects of the reduction
      of production of SCCPs in Europe and the increasingly stringent regulation.
      However, the decline in soil is slow with a halving time of 18 years.
      Concentrations of MCCPs have continuously increased in soil over the entire
      period 1989-2014, with a doubling between 2009 and 2014. The concentrations of
      MCCPs have surpassed those of SCCPs, showing their relevance today, partly as
      replacements for SCCPs. Soil concentrations of PCBs peaked in 1999, i.e. three
      decades later than worldwide production and use of PCBs, but earlier than the
      entry into force of the Stockholm Convention. PCBs follow a decline in soil with
      a halving time of approx. 8 years. This study shows the usefulness of sample
      archives for the reconstruction and interpretation of time trends of persistent
      environmental contaminants.

PMID- 27876230
TI  - Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for
      Patients With Advanced Non-Small-cell Lung Cancer: A Systematic Review and Meta
      analysis.
AB  - Randomized clinical trials (RCTs) of concurrent epidermal growth factor receptor
      tyrosine kinase inhibitors (EGFR-TKIs) plus chemotherapy for unselected patients
      with advanced non-small-cell lung cancer (NSCLC) produced negative results.
      Intercalated administration could avoid the reduction of chemotherapy activity
      due to G1 cell-cycle arrest from EGFR-TKIs. A PubMed search was performed in
      December 2015 and updated in February 2016. The references from the selected
      studies were also checked to identify additional eligible trials. Furthermore,
      the proceedings of the main international meetings were searched from 2010
      onward. We included RCTs comparing chemotherapy intercalated with an EGFR-TKI
      versus chemotherapy alone for patients with advanced NSCLC. Ten RCTs were
      eligible (6 with erlotinib, 4 with gefitinib): 39% of patients had a known EGFR
      mutational status, 43% of whom EGFR mutation positive. The intercalated
      combination was associated with a significant improvement in overall survival
      (OS; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.95; P = .01),
      progression-free survival (PFS; HR, 0.60; 95% CI, 0.53-0.68; P < .00001), and
      objective response rate (ORR; odds ratio [OR], 2.70; 95% CI, 2.08-3.49; P <
      .00001). Considering only first-line trials, similar differences were found in OS
      (HR, 0.85; 95% CI, 0.72-1.00; P = .05), PFS (HR, 0.63; 95% CI, 0.55-0.73; P <
      .00001), and ORR (OR, 2.21; 95% CI, 1.65-2.95; P < .00001). In EGFR mutation
      positive patients, the addition of an intercalated EGFR-TKI produced a
      significant benefit in PFS (129 patients; HR, 0.24; 95% CI, 0.16-0.37; P <
      .00001) and ORR (168 patients; OR, 11.59; 95% CI, 5.54-24.25; P < .00001). In
      patients with advanced NSCLC, chemotherapy plus intercalated EGFR-TKIs was
      superior to chemotherapy alone, although a definitive interpretation was
      jeopardized by the variable proportion of patients with EGFR mutation-positive
      tumors included.

PMID- 27876232
TI  - Hypercoagulation and complement: Connected players in tumor development and
      metastases.
AB  - Hypercoagulation is a common feature of several tumors to the extent that
      individuals with coagulation defects often present with occult visceral cancers.
      Recent evidence has shown that hypercoagulation is not just a mere secondary
      effect due to the presence of the tumor, rather it actively contributes to tumor
      development and dissemination. Among the numerous mechanisms that can contribute
      to cancer-associated hypercoagulation, the ones involving immune-mediated
      processes are gaining increasing attention. In particular, complement cascade and
      hypercoagulation are one inducing the other in a vicious circle that involves
      neutrophil extracellular traps (NETs) formation. Together, in this feedback loop,
      they can promote the protumorigenic phenotype of immune cells and the protection
      of tumor cells from immune attack, ultimately favouring tumor development,
      progression and metastases formation. In this review, we summarize the role of
      these processes in cancer development and highlight new possible intervention
      strategies based on anticoagulants that can arrest this vicious circle.

PMID- 27876231
TI  - Paternal preconception alcohol exposure imparts intergenerational alcohol-related
      behaviors to male offspring on a pure C57BL/6J background.
AB  - While alcohol use disorder (AUD) is a highly heritable condition, the basis of
      AUD in families with a history of alcoholism is difficult to explain by genetic
      variation alone. Emerging evidence suggests that parental experience prior to
      conception can affect inheritance of complex behaviors in offspring via non
      genomic (epigenetic) mechanisms. For instance, male C57BL/6J (B6) mice exposed to
      chronic intermittent vapor ethanol (CIE) prior to mating with Strain 129S1/SvImJ
      ethanol-naive females produce male offspring with reduced ethanol-drinking
      preference, increased ethanol sensitivity, and increased brain-derived
      neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). In the
      present study, we tested the hypothesis that these intergenerational effects of
      paternal CIE are reproducible in male offspring on an inbred B6 background. To
      this end, B6 males were exposed to 6 weeks of CIE (or room air as a control)
      before mating with ethanol-naive B6 females to produce ethanol (E)-sired and
      control (C)-sired male and female offspring. We observed a sex-specific effect,
      as E-sired males exhibited decreased two-bottle free-choice ethanol-drinking
      preference, increased sensitivity to the anxiolytic effects of ethanol, and
      increased VTA BDNF expression; no differences were observed in female offspring.
      These findings confirm and extend our previous results by demonstrating that the
      effects of paternal preconception ethanol are reproducible using genetically
      identical, inbred B6 animals.

PMID- 27876233
TI  - Role of platelets in neutrophil extracellular trap (NET) production and tissue
      injury.
AB  - In addition to their well-known role as the cellular mediator of thrombosis,
      numerous studies have identified key roles for platelets during various disease
      processes. Importantly, platelets play a critical role in the host immune
      response, directly interacting with, and eliminating pathogens, from the blood
      stream. In addition to pathogen clearance, platelets also contribute to leukocyte
      recruitment at sites of infection and inflammation, and modulate leukocyte
      activity. Platelet interaction with activated neutrophils is a potent inducer of
      neutrophil extracellular trap (NET). NETs consist of a diffuse, sticky web of
      extracellular DNA, nuclear and granular proteins, and serve to ensnare and kill
      pathogens. In addition to catching pathogens, the cytotoxic molecules and
      proteases on NETs have the potential to inflict significant tissue damage.
      Additionally, NET components have been suggested to be key activators of
      infection-induced coagulopathy. These critical roles, at the interface between
      hemostasis and immunity, highlight the need for balance in the platelet response;
      too little platelet activity results in bleeding and immune deficit, too much
      leads to tissue pathogenesis. In this review, we highlight recent advances in our
      understanding of the role platelets play in inflammation, the link between
      platelets and NETs and the role platelets play in disease pathogenesis.

PMID- 27876234
TI  - Identification of a Remodeled Neo-tendon After Arthroscopic Latarjet Procedure.
AB  - PURPOSE: To macroscopically, histologically, and radiologically describe a time
      dependent remodeling process of a neo-tendon or -ligament in the shoulder after
      the arthroscopic Latarjet procedure. METHODS: During follow-up surgery after the
      arthroscopic Latarjet procedure, 17 shoulders in 16 patients were evaluated for a
      remodeled tendon-like structure. The mean overall follow-up period was 27.4
      months. The mean time between the arthroscopic Latarjet procedure and revision
      was 11.6 months. All shoulders were evaluated with magnetic resonance imaging,
      and seven histologic specimens were obtained during revision surgery. RESULTS: A
      distinct, oriented strand of tissue was found in 16 of 17 shoulders on revision
      surgery. Postoperative magnetic resonance imaging analyses showed a signal-free,
      longitudinal tendon-like structure originating at the tip of the acromion,
      traversing the space of the former subcoracoid bursa to attach in the course of
      the transposed conjoint tendon or the proximal short head of the biceps.
      Histologic analysis of seven specimens showed a characteristic timeline of
      remodeling. CONCLUSIONS: A tendon- or ligament-like structure is remodeled
      between the anterior bottom tip of the acromion and the transposed coracoid
      process in a time-dependent manner after the arthroscopic Latarjet procedure.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 27876235
TI  - High Altitude Is an Independent Risk Factor for Postoperative Symptomatic Venous
      Thromboembolism After Knee Arthroscopy: A Matched Case-Control Study of Medicare
      Patients.
AB  - PURPOSE: To use a national database of Medicare patients to evaluate the
      association of uncomplicated knee arthroscopy performed at high altitude with the
      incidence of postoperative venous thromboembolism (VTE). METHODS: The 100%
      Medicare Standard Analytical File database was queried for all patients
      undergoing isolated arthroscopic partial meniscectomy and/or chondroplasty from
      2005-2012. Patients with more complex open or additional arthroscopic knee
      procedures, a personal history of VTE, or any hypercoagulable state were
      excluded. The result of this query was then stratified by the altitude of the
      hospital ZIP code in which the procedure was performed. The appropriate patients
      were placed into a high-altitude group (>=4,000 ft) and matched to patients who
      underwent the same procedures at an altitude less than or equal to 100 ft on the
      basis of age, sex, and medical comorbidities. The rate of VTE was then assessed
      for both the high-altitude and matched low-altitude patients within 30 days and
      90 days postoperatively. RESULTS: The rate of combined VTE (deep venous
      thrombosis [DVT] and/or pulmonary embolism [PE]) (odds ratio [OR], 2.0; P =
      .0003), the rate of PE (OR, 2.5; P = .0099), and the rate of DVT (OR, 1.7; P =
      .0066) within 30 days were all significantly higher in patients with procedures
      performed at high altitude compared with matched patients with the same
      procedures performed at low altitude. At 90 days postoperatively, similarly
      elevated risks of VTE, PE, and DVT were found in patients with procedures
      performed at high altitude. CONCLUSIONS: In this study of knee arthroscopy in
      Medicare patients, a procedure performed at an altitude >=4,000 ft was a
      significant risk factor for the development of postoperative VTE compared with
      matched patients undergoing the same procedure at an altitude less than or equal
      to 100 ft. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

PMID- 27876237
TI  - A Real Fifth Dimension?

PMID- 27876236
TI  - Immunohistochemical comparative analysis of lymphatic vessel density and VEGF-C
      expression in squamous cell carcinomas of the tongue between young and old
      patients.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) of the oral cavity is a malignant
      epithelial tumor that most commonly involves the tongue, and mainly affects men
      between the fifth and seventh decades of life. This study compared the lymphatic
      vessel density and VEGF-C expression in SCCs of the tongue between young and old
      patients. METHODS: Thirty-four SCCs of the tongue, 17 diagnosed in young patients
      (<=40y) and 17 diagnosed in old patients (>50y), were evaluated by
      immunohistochemistry. Lymphatic microdensity was determined based on the number
      of vessels immunoreactive to anti-D2-40 antibody. The percentage of neoplastic
      cells exhibiting cytoplasmic staining for VEGF-C was established for each case.
      RESULTS: Assessment of intratumoral lymphatic microdensity (ILMD) disclosed a
      median number of 6.20 lymphatic vessels in young patients and of 6.60 in old
      patients (p=0.809). Analysis of peritumoral lymphatic microdensity (PLMD)
      revealed a median number of 3.60 lymphatic vessels in young patients and of 3.40
      in old patients (p=0.769). In the tumor core, analysis of the percentage of
      immunopositive cells for VEGF-C revealed a median number of 95.95% in young
      patients and of 55.48% in old patients (p<0.001). In the deep invasive front, the
      median number of immunopositive cells for VEGF-C was 97.93% in young patients and
      66.09% in old patients (p<0.001). CONCLUSIONS: The results of this study suggest
      that the more aggressive biological behavior of SCC of the tongue in young
      patients may be related to a higher expression of VEGF-C.

PMID- 27876238
TI  - Thermography Examination of Abdominal Area Skin Temperatures in Individuals With
      and Without Focal-Onset Epilepsy.
AB  - : Early osteopathic theory and practice, and the work of the medical intuitive
      Edgar Cayce suggested that the abdominal areas of individuals with epilepsy would
      manifest "cold spots." The etiology for this phenomenon was thought to be
      abdominal adhesions caused by inflammation and viscero-somatic reflexes caused by
      adhesions or injury to visceral or musculoskeletal system structures. Indeed,
      until that advent of electroencephalography in the 1930s, medical practice
      regarding epilepsy focused on abdominal neural and visceral structures. Following
      two hypotheses were formulated to evaluate any abdominal temperature phenomena:
      (1) an abdominal quadrant division analysis would find one or more quadrants
      "colder" in the focal-onset epilepsy group (ICD9-CM 345.4 and 345.5) compared to
      controls. (2) Total abdominal areas of individuals with focal-onset epilepsy
      wound be colder than a control group. METHODS: Overall, 50 patients with the
      diagnosis of focal-onset epilepsy were recruited from the office of the Epilepsy
      Foundation of Florida and 50 control subjects with no history of epilepsy were
      recruited through advertising to the public. Under controlled room conditions all
      subjects had infrared thermographic images made and recorded by Med-Hot Model MH
      731 FLIR equipment. RESULTS: There were no significant demographic difference
      between experimental patients and control subjects, though the control group
      tended to be younger and more often male; however, these were controlled for in
      all analyses. In the quadrant analysis, there were significant differences in
      that more epileptic patients had colder left upper abdominal quadrant
      temperatures than the control group (66.8% versus 44.9%; P = .030). In the total
      abdominal analysis, however, there were no significant differences. DISCUSSION:
      The results support the hypothesis that individuals with focal-onset epilepsy
      have colder abdominal areas. If substantiated in further research, present study
      results will require further examination of the mechanisms of action for
      epilepsy, and suggest the need for re-examination of older formulations of
      abdominal epilepsy, including the place of abdominal injury, inflammation, and
      adhesions in epileptic pathology. The concept of somato-visceral and viscero
      somatic neurological interactions is one of the possible mechanisms underlying
      the "cold spot" findings and warrants further consideration.

PMID- 27876239
TI  - Case Reports of Idiopathic Thrombocytopenia Unresponsive to First-Line Therapies
      Treated With Traditional Herbal Medicines Based on Syndrome Differentiation.
AB  - The objective of our study is to present two cases showing the effects of
      traditional Korean herbal medicines based on traditional Korean medicine (TKM)
      for the treatment of immune thrombocytopenic purpura (ITP). One patient showed no
      response to treatment with steroids and an immunosuppressive agent. Moreover,
      liver toxicity and side effects of steroids were evident. However, after he
      ceased conventional treatment and started to take an herbal medicine, his liver
      function normalized and the steroid side effects resolved. Ultimately, he
      achieved complete remission. Another patient with ITP had sustained remission
      after steroid therapy in childhood, but extensive uterine bleeding and
      thrombocytopenia recurred when she was 16 years old. She was managed with
      steroids again for 2 years, but severe side effects occurred, and eventually she
      ceased taking steroids. She refused a splenectomy, and was then treated with a
      herbal medicine for 7 months, ultimately leading to sustained remission again.
      Many patients with resistance to first-line treatments tend to be reluctant to
      undergo a splenectomy, considered a standard second-line treatment. In
      conclusion, herbal medicines, based on TKM, may offer alternative treatments for
      persistent or chronic ITP that is resistant to existing first-line treatments.

PMID- 27876240
TI  - Variable neighborhood search to solve the vehicle routing problem for hazardous
      materials transportation.
AB  - This work focuses on the Heterogeneous Fleet Vehicle Routing problem (HFVRP) in
      the context of hazardous materials (HazMat) transportation. The objective is to
      determine a set of routes that minimizes the total expected routing risk. This is
      a nonlinear function, and it depends on the vehicle load and the population
      exposed when an incident occurs. Thus, a piecewise linear approximation is used
      to estimate it. For solving the problem, a variant of the Variable Neighborhood
      Search (VNS) algorithm is employed. To improve its performance, a post
      optimization procedure is implemented via a Set Partitioning (SP) problem. The SP
      is solved on a pool of routes obtained from executions of the local search
      procedure embedded on the VNS. The algorithm is tested on two sets of HFVRP
      instances based on literature with up to 100 nodes, these instances are modified
      to include vehicle and arc risk parameters. The results are competitive in terms
      of computational efficiency and quality attested by a comparison with Mixed
      Integer Linear Programming (MILP) previously proposed.

PMID- 27876241
TI  - Recycling of typical difficult-to-treat e-waste: Synthesize zeolites from waste
      cathode-ray-tube funnel glass.
AB  - The disposal of waste cathode ray-tubes (CRTs) from old televisions and discarded
      computer monitors has become a major environmental concern worldwide. In this
      work, an open-loop recycling method was developed to synthesize zeolites using
      CRT funnel glass as the raw material. The effects of hydrothermal temperatures
      and pressure, n(SiO2/Al2O3) molar ratios and hydrothermal time on the resulting
      products were investigated. The results indicated that hydrothermal temperatures
      and pressure played critical roles in zeolite synthesis. Amorphous phases were
      detected at lower temperatures (80-100 degrees C) and pressure (0.47-1.01bar)
      with n(SiO2/Al2O3)=2.0. At the temperature of 110 degrees C (pressure 1.43bar),
      NaA formed with a mixture of NaP1 and Faujasite. With further increase in the
      temperature and pressure, the unstable NaA and Faujasite disappeared, and
      Hydroxysodalite developed. The influence of n(SiO2/Al2O3) ratios on resulting
      products revealed a single phase of NaA was formed at the ratio of 1.5 and a
      mixture of NaA and Faujasite at the ratio of 2.0. Prolonging hydrothermal time,
      however, could promote zeolite crystallization, and NaA gradually developed with
      an increase in the time from 2 to 6h at n(SiO2/Al2O3)=1.5. By comparison,
      crystallization phases were observed only when the time was longer than 8h at
      n(SiO2/Al2O3)=2.0.

PMID- 27876242
TI  - Corrigendum to "Pilot study on arsenic removal from groundwater using a small
      scale reverse osmosis system-Towards sustainable drinking water production'' [J.
      Hazard. Mater. 318 (2016) 671-678].

PMID- 27876243
TI  - Quinone-modified NH2-MIL-101(Fe) composite as a redox mediator for improved
      degradation of bisphenol A.
AB  - A novel quinone-modified metal-organic frameworks NH2-MIL-101(Fe) was synthesized
      using a simple chemical method under mild condition. The introduced 2
      anthraquinone sulfonate (AQS) can be covalently modified with NH2-MIL-101(Fe) and
      acts as a redox mediator to enhance the degradation of bisphenol A (BPA) via
      persulfate activation. The obtained AQS-NH-MIL-101(Fe) was characterized by
      Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron
      microscopy, X-ray photoelectron spectra, cyclic voltammetry and electrochemical
      impedance spectroscopy. AQS-NH-MIL-101(Fe) exhibited better catalytic performance
      compared with NH2-MIL-101(Fe) and NH2-MIL-101(Fe) with free AQS (NH2-MIL
      101(Fe)/AQS). That is, AQS-NH-MIL-101(Fe) was proved to be the most effective in
      that more than 97.7% of BPA was removed. The degradation rate constants (k) of
      AQS-NH-MIL-101(Fe) was 9-fold higher than that of NH2-MIL-101(Fe) and 7-fold
      higher than NH2-MIL-101(Fe)/AQS, indicating that AQS is a great electron-transfer
      mediator when modified with NH2-MIL-101(Fe). Based on the above results, the
      possible mechanism of catalytic reaction has been investigated in view of the
      trapping experiments. In addition, the AQS-NH-MIL-101(Fe) catalyst exhibited
      excellent stability and can be used several times without significant
      deterioration in performance.

PMID- 27876244
TI  - Overexpression of OsSPL9 enhances accumulation of Cu in rice grain and improves
      its digestibility and metabolism.

PMID- 27876245
TI  - Perioperative medicine and Taiwan National Health Insurance Research Database.
AB  - "Big data", characterized by 'volume', 'velocity', 'variety', and 'veracity',
      being routinely collected in huge amounts of clinical and administrative
      healthcare-related data are becoming common and generating promising viewpoints
      for a better understanding of the complexity for medical situations. Taiwan
      National Health Insurance Research Database (NHIRD), one of large and
      comprehensive nationwide population reimbursement databases in the world,
      provides the strength of sample size avoiding selection and participation bias.
      Abundant with the demographics, clinical diagnoses, and capable of linking
      diverse laboratory and imaging information allowing for integrated analysis,
      NHIRD studies could inform us of the incidence, prevalence, managements,
      correlations and associations of clinical outcomes and diseases, under the
      universal coverage of healthcare used. Perioperative medicine has emerged as an
      important clinical research field over the past decade, moving the categorization
      of the specialty of "Anesthesiology and Perioperative Medicine". Many studies
      concerning perioperative medicine based on retrospective cohort analyses have
      been published in the top-ranked journal, but studies utilizing Taiwan NHIRD were
      still not fully visualized. As the prominent growth curve of NHIRD studies, we
      have contributed the studies covering surgical adverse outcomes, trauma, stroke,
      diabetes, and healthcare inequality, etc., to this ever growing field for the
      past five years. It will definitely become a trend of research using Taiwan NHIRD
      and contributing to the progress of perioperative medicine with the recruitment
      of devotion from more research groups and become a famous doctrine.

PMID- 27876246
TI  - Corrections.

PMID- 27876248
TI  - Pirfenidone and mortality in idiopathic pulmonary fibrosis.

PMID- 27876247
TI  - Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical
      trials in idiopathic pulmonary fibrosis.
AB  - BACKGROUND: In clinical trials of idiopathic pulmonary fibrosis, rates of all
      cause mortality are low. Thus prospective mortality trials are logistically very
      challenging, justifying the use of pooled analyses or meta-analyses. We did
      pooled analyses and meta-analyses of clinical trials of pirfenidone versus
      placebo to determine the effect of pirfenidone on mortality outcomes over 120
      weeks. METHODS: We did a pooled analysis of the combined patient populations of
      the three global randomised phase 3 trials of pirfenidone versus placebo-Clinical
      Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of
      Efficacy and Safety Outcomes (CAPACITY 004 and 006; trial durations 72-120 weeks)
      and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic
      Pulmonary Fibrosis (ASCEND 016; 52 weeks)-for all-cause mortality, treatment
      emergent all-cause mortality, idiopathic-pulmonary-fibrosis-related mortality,
      and treatment-emergent idiopathic-pulmonary-fibrosis-related mortality at weeks
      52, 72, and 120. We also did meta-analyses of these data and data from two
      Japanese trials of pirfenidone versus placebo-Shionogi Phase 2 (SP2) and Shionogi
      Phase 3 (SP3; trial durations 36-52 weeks). FINDINGS: At week 52, the relative
      risk of death for all four mortality outcomes was significantly lower in the
      pirfenidone group than in the placebo group in the pooled population (all-cause
      mortality hazard ratio [HR] 0.52 [95% CI 0.31-0.87; p=0.0107]; treatment-emergent
      all-cause mortality 0.45 [0.24-0.83; 0.0094]; idiopathic-pulmonary-fibrosis
      related mortality 0.35 [0.17-0.72; 0.0029]; treatment-emergent idiopathic
      pulmonary-fibrosis-related mortality 0.32 [0.14-0.76; 0.0061]). Consistent with
      the pooled analysis, meta-analyses for all-cause mortality at week 52 also showed
      a clinically relevant and significant risk reduction in the pirfenidone group
      compared with the placebo group. Over 120 weeks, we noted significant differences
      in the pooled analysis favouring pirfenidone therapy compared with placebo for
      treatment-emergent all-cause mortality (p=0.0420), idiopathic-pulmonary-fibrosis
      related mortality (0.0237), and treatment-emergent idiopathic-pulmonary-fibrosis
      related (0.0132) mortality; similar results were shown by meta-analyses.
      INTERPRETATION: Several analytic approaches demonstrated that pirfenidone therapy
      is associated with a reduction in the relative risk of mortality compared with
      placebo over 120 weeks. FUNDING: F Hoffmann-La Roche/Genentech.

PMID- 27876249
TI  - Synthesis, anti-proliferative activity, SAR study, and preliminary in vivo
      toxicity study of substituted N,N'-bis(arylmethyl)benzimidazolium salts against a
      panel of non-small cell lung cancer cell lines.
AB  - A series of N,N'-bis(arylmethyl)benzimidazolium salts have been synthesized and
      evaluated for their in vitro anti-cancer activity against select non-small cell
      lung cancer cell lines to create a structure activity relationship profile. The
      results indicate that hydrophobic substituents on the salts increase the overall
      anti-proliferative activity. Our data confirms that naphthylmethyl substituents
      at the nitrogen atoms (N1(N3)) and highly lipophilic substituents at the carbon
      atoms (C2 and C5(C6)) can generate benzimidazolium salts with anti-proliferative
      activity that is comparable to that of cisplatin. The National Cancer Institute's
      Developmental Therapeutics Program tested 1, 3-5, 10, 11, 13-18, 20-25, and 28-30
      in their 60 human tumor cell line screen. Results were supportive of data
      observed in our lab. Compounds with hydrophobic substituents have higher anti
      cancer activity than compounds with hydrophilic substituents.

PMID- 27876250
TI  - Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl
      aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2
      CH3.
AB  - A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted
      in phenyl ring with 4-Cl, 4-CH3 or 2-CH3 was designed, synthesized and evaluated
      for anticonvulsant activity in rodent models of seizures: maximal electroshock
      (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and 6-Hz test. There
      were identified three most active compounds: S-(2E)-N-(1-hydroxypropan-2-yl)-3-(2
      methylphenyl)prop-2-enamide (5) (ED50 MES=42.56, ED50 scPTZ=58.38, ED50 6-Hz
      44mA=42.27mg/kg tested in mice after intraperitoneal (i.p.) administration); R,S
      (2E)-3-(4-chlorophenyl)-N-(1-hydroxybutan-2-yl)prop-2-enamide (6) (ED50
      MES=53.76, ED50 scPTZ=90.31, ED50 6-Hz 44mA=92.86mg/kg mice, i.p.); and R,S-(2E)
      3-(4-chlorophenyl)-N-(2-hydroxypropyl)prop-2-enamide (11) (ED50 MES=55.58, ED50
      scPTZ=102.15, ED50 6-Hz 44mA=51.27mg/kg mice, i.p.). Their structures and
      configurations were confirmed by crystal X-ray diffraction method. The structure
      activity studies among the tested series showed that chlorine atom in position
      para or methyl group in position ortho of phenyl ring were beneficial for
      anticonvulsant activity. Methyl group in position para of phenyl ring decreased
      anticonvulsant activity in reported series of cinnamamide derivatives.

PMID- 27876251
TI  - [Food protein-induced enterocolitis syndrome: A case report of diarrhea with
      hypovolemic shock and methemoglobinemia].
AB  - We report on the case of a young infant with chronic diarrhea that worsened and
      turned into hypovolemic shock with methemoglobinemia. We underline and discuss
      the main features of food protein-induced enterocolitis syndrome (FPIES). FPIES
      is a non-IgE-mediated food allergy involving tumor necrosis factor-alpha (TNF
      alpha). Many triggering foods exist but cow's milk, as in the case reported
      herein, is one of the most frequent. It can start early or be delayed and start
      around the average age of 5 months. Symptoms are nonspecific with diarrhea and
      vomiting, but in the presence of methemoglobinemia, the diagnosis must be
      seriously considered. The oral food challenge remains the gold standard to
      confirm the diagnosis if there is still a doubt. Treatment of FPIES associates
      emergency treatment of acute dehydration with the prevention of relapses by
      avoiding the suspected protein.

PMID- 27876252
TI  - Clinical characteristics in cholinergic urticaria with palpebral angioedema:
      Report of 15 cases.

PMID- 27876253
TI  - The Impact of Surgical Technique on Patient Reported Outcome Measures and Early
      Complications After Total Hip Arthroplasty.
AB  - BACKGROUND: This study examines patient and surgeon reported outcome measures,
      complications during index admission, length of stay (LOS), and discharge
      disposition in a series of total hip replacements (THR) performed via the direct
      anterior (DA) or posterolateral (PL) approach. METHODS: Five surgeons performed
      2698 total hip replacements (1457 DA vs 1241 PL) between January 2010 and June
      2015. Complications during index admission were recorded using billing and claims
      data. Harris Hip Scores (HHS) and Hip disability and Osteoarthritis Outcome
      Scores (HOOS) were collected in a subset of patients. RESULTS: Patients in the DA
      group had shorter LOS (2.3 DA vs 2.7 PL days, P < .001) and a larger proportion
      of patient discharges to home (79.0% DA vs 68.7% PL, P < .001). Surgical (0.75%
      DA vs 0.73% PL, P = .961) and medical (8.4% DA vs 8.1% PL, P = .766)
      complications during index admission were equivalent between groups. HHS (n =
      462) favored the DA group at an early follow-up (P < .001), but did not differ at
      1 year (P = .478). Logistic regression revealed that patients in the DA group
      were more likely to report no pain, no limp, walk unlimited distances, and climb
      stairs without the use of the railing at 3- to 6-month follow-up (P < .001).
      HOOSs were equivalent at all follow-ups regardless of approach. CONCLUSION:
      Patients in the DA group had shorter LOS and were more likely to be discharged
      home. The DA group had better HHS at 3- to 6-month follow-up than patients in the
      PL group, with no difference in medical or surgical complications during index
      admission.

PMID- 27876254
TI  - Is Selectively Not Resurfacing the Patella an Acceptable Practice in Primary
      Total Knee Arthroplasty?
AB  - BACKGROUND: To resurface or not to resurface the patella remains a controversy in
      total knee arthroplasty (TKA). The purpose of this study was to assess the long
      term outcomes associated with selectively not resurfacing the patella. METHODS:
      This was a historical cohort study of 15,497 patients with 21,371 primary TKA
      procedures performed at a single institution between 1985 and 2010. The cohort
      included 402 (2%) knees with unresurfaced patellae and 20,969 knees with all
      polyethylene patellae designs. Reasons for not resurfacing the patella were
      documented. Multivariable Cox regression analyses were used to estimate the risk
      of complications and revisions among procedures with unresurfaced patellae.
      RESULTS: According to the surgeon, reasons for not resurfacing were normal
      cartilage (226, 56%), young patient (30, 8%), thin patella (53, 13%), and
      surgeons' choice (93, 23%). In age, sex, and calendar year-adjusted analyses, the
      risk of complications (hazard ratio [HR]: 1.25, 95% confidence interval [CI]:
      1.06, 1.46) and all-cause revisions (HR: 1.39, 95% CI: 1.02, 1.89) were
      significantly higher after TKA with unresurfaced patellae. However, after
      adjusting for femoral component types and operative diagnoses, these associations
      were no longer significant. The only group with significantly worse outcomes were
      those with a thin patellae with increased risk of complications (HR: 2.66, 95%
      CI: 1.70, 4.17) and revisions (HR: 5.94, 95% CI: 2.35, 15.02). Yet, the excess
      risk in the thin patellae group was mainly due to infections, and not related to
      unresurfaced patellae. CONCLUSION: Selectively not resurfacing the patella seemed
      to provide similar results compared with routine resurfacing.

PMID- 27876255
TI  - Patient and Perioperative Variables Affecting 30-Day Readmission for Surgical
      Complications After Hip and Knee Arthroplasties: A Matched Cohort Study.
AB  - BACKGROUND: Changes in reimbursement for total hip and knee arthroplasties (THA
      and TKA) have placed increased financial burden of early readmission on hospitals
      and surgeons. Our purpose was to characterize factors of 30-day readmission for
      surgical complications after THA and TKA at a single, high-volume orthopedic
      specialty hospital. METHODS: Patients with a diagnosis of osteoarthritis and who
      were readmitted within 30 days of their unilateral primary THA or TKA procedure
      between 2010 and 2014. Readmitted patients were matched to nonreadmitted patients
      1:2. Patient and perioperative variables were collected for both cohorts. A
      conditional logistic regression was performed to assess both the patient and
      perioperative factors and their predictive value toward 30-day readmission.
      RESULTS: Twenty-one thousand eight hundred sixty-four arthroplasties (THA =
      11,105; TKA = 10,759) were performed between 2010 and 2014 at our institution, in
      which 60 patients (THA = 37, TKA = 23) were readmitted during this 5-year period.
      The most common reasons for readmission were fracture (N = 14), infection (N =
      14), and dislocation (N = 9). Thirty-day readmission for THA was associated with
      increased procedure time (P = .05), length of stay (LOS) shorter than 2 days (P =
      .04), discharge to a skilled nursing facility (P = .05), and anticoagulation use
      other than aspirin (P = .02). Thirty-day readmission for TKA was associated with
      increased tourniquet time (P = .02), LOS <3 days (P < .01), and preoperative
      depression (P = .02). In the combined THA/TKA model, a diagnosis of depression
      increased 30-day readmission (odds ratio 3.5 [1.4-8.5]; P < .01). CONCLUSION:
      Risk factors for 30-day readmission for surgical complications included short
      LOS, discharge destination, increased procedure/tourniquet time, potent
      anticoagulation use, and preoperative diagnosis of depression. A focus on risk
      factor modification and improved risk stratification models are necessary to
      optimize patient care using readmission rates as a quality benchmark.

PMID- 27876256
TI  - Do Changes in the Production Process Affect the Outcome of Ceramic Liners: A 3
      Year Follow-Up Study.
AB  - BACKGROUND: In 2011, the current liner was withdrawn from the market because of
      the potential risk for liner fracture secondary to increased pressures used to
      assemble the metal locking ring. The present study provides a short-term follow
      up of patients with this implant. METHODS: We retrospectively evaluated 63
      consecutive hips in 53 patients operated by a single surgeon using a recalled
      ceramic-on-ceramic bearing. There were 30 women and 23 men with an average age of
      50.6 years (range 20.3-63.5 years). The mean follow-up was 36.8 months. RESULTS:
      Six hips in 6 patients were revised (9.5%) because of a liner-fracture during the
      follow-up period. All liner fractures were identified on computer tomography
      imaging. Nine patients had self-reported episodes of squeaking (14.3%). All 6
      patients that underwent revision surgery for liner fracture described squeaking
      before revision. There were no revisions for other causes. Two of the revised
      patients had a subsequent dislocation (33%). CONCLUSION: The recalled ceramic
      liner lots have an increased liner fracture rate. Patients with mechanical
      symptoms or squeaking should undergo computer tomography to rule out liner
      facture.

PMID- 27876257
TI  - Tubular aggregate myopathy with features of Stormorken disease due to a new STIM1
      mutation.
AB  - STIM1 is a reticular Ca2+ sensor composed of a luminal and a cytosolic domain.
      Missense mutations in the luminal domain have been associated with tubular
      aggregate myopathy (TAM), while cytosolic mutations can cause Stormorken
      syndrome, a multisystemic disease associating TAM with asplenia,
      thrombocytopenia, miosis, ichthyosis, short stature and dyslexia. Here we present
      the case of a 41-year-old female complaining of exercise intolerance. Clinical
      examination showed short stature, scoliosis, proximal muscle weakness with lower
      limb predominance, and ophthalmoplegia. Laboratory tests revealed hypocalcemia,
      mild anemia and elevated creatine kinase (CK) levels. Whole-body muscle magnetic
      resonance imaging (MRI) revealed asplenia. Muscle biopsy was consistent with TAM.
      STIM1 gene analysis disclosed the novel c.252T>A, p.D84E missense mutation which
      was shown to induce constitutive STIM1 clustering in a functional study. This
      study reports a novel STIM1 mutation located in the Ca2+-binding EF domain
      causing TAM with features of Stormorken syndrome.

PMID- 27876260
TI  - Editorial overview: Endocrine and metabolic diseases: Adipocyte dysfunction fuels
      signalings for breast cancer progression.

PMID- 27876258
TI  - Normal saline instillation before suctioning: A meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: For airway management of intensive care unit (ICU) patients who are
      intubated, a 5-10-mL bolus of sterile normal saline (NS) solution is commonly
      instilled into an endotracheal or tracheostomy tube before suctioning. However,
      NS instillation has been associated with adverse events such as dyspnea,
      increasing heart rate, decreasing of oxygenation, blood pressure, and other vital
      parameters. OBJECTIVE: To conduct a systematic review and meta-analysis of
      randomized controlled trials (RCTs) to evaluate the necessity of NS instillation
      before suctioning in ICU patients. DATA SOURCES: The PubMed, Embase, Cochrane
      Library, and Scopus databases and the ClinicalTrials.gov registry were searched
      for studies published before May 2016. REVIEW METHODS: RCTs evaluating the
      outcome of NS instillation before suctioning in ICU patients undergoing
      endotracheal intubation or tracheostomy were included. Individual effect sizes
      were standardised, and a meta-analysis was conducted to calculate the pooled
      effect size by using a random-effect model. The primary outcome was the oxygen
      saturation immediately and 2 and 5min after suctioning. The secondary outcomes
      were the heart rate and blood pressure after suctioning. RESULTS: We reviewed 5
      RCTs including 337 patients. Oxygen saturation was significantly higher in the
      non-NS group than in the NS group 5min after suctioning. The pooled mean
      difference in oxygen saturation was -1.14 (95% confidence interval: -2.25 to 
      0.03). The heart rate and blood pressure did not differ significantly between the
      non-NS and NS groups. CONCLUSION: NS instillation before suctioning does not
      benefit patients undergoing endotracheal intubation or tracheostomy. Moreover, it
      reduces oxygen saturation 5min after suction. However, our reviewed studies had a
      low methodological quality. Thus, additional studies involving large-scale RCTs
      are warranted.

PMID- 27876259
TI  - A Diagnostic Dilemma for the Pediatrician: Radiolucent Tracheobronchial Foreign
      Body.
AB  - BACKGROUND: The purpose of this study is to determine the role of clinical
      history, physical examinations, and radiological findings in the evaluation of
      patients with suspected radiolucent foreign body aspiration. METHODS: The medical
      records of 236 children (under the age of 18 years), on whom a rigid bronchoscopy
      was performed between 1999 and 2015 because of suspected radiolucent foreign body
      aspiration, were analyzed retrospectively. Sensitivity, specificity, positive and
      negative predictive values of clinical history, physical examinations, and
      radiological findings were evaluated. RESULTS: In 71.1% of all cases, the
      children were under the age of 3 years. The bronchoscopy showed the presence of a
      foreign body in 52.9% of cases, with the locations of the foreign bodies being as
      follows: (1) right main bronchus, 47.2%; (2) left main bronchus, 36.0%; (3)
      trachea, 11.2%; (4) both bronchi, 5.6%. Organic foreign bodies were found in 78%
      of the patients, whereas inorganic foreign bodies were detected in 22% of the
      patients. The sensitivity and specificity of clinical history, physical
      examinations, and radiological findings were 98.4% and 54.9%, 47.2% and 74.7%,
      and 35.2% and 92.7%, respectively. CONCLUSION: Tracheobronchial foreign body
      aspirations usually occur prior to the age of 3 years, with the most frequently
      aspirated foreign bodies being food or items of a radiolucent nature. Clinical
      history, physical examinations, and radiological findings are not able to detect
      the presence of a radiolucent foreign body aspiration in children. Therefore, a
      bronchoscopy should be performed on children in whom a choking event has been
      witnessed, even in cases of normal radiological and clinical findings.

PMID- 27876262
TI  - New 'refined' criteria for the electrocardiographic assessment of athletes.

PMID- 27876263
TI  - The Prognosis of Thebesian Veins Can Be Obfuscated by Conflating the Vessels
      (Veins) of Thebesius With Coronary Artery-Cameral Connections.

PMID- 27876261
TI  - Cartilage repair strategies in the knee: A survey of Turkish surgeons.
AB  - OBJECTIVES: The purpose of this study was to analyze the trends in cartilage
      repair strategies among Turkish orthopedic surgeons for isolated focal
      (osteo)chondral lesions of the knee joint. MATERIALS AND METHODS: A web-based
      survey of 21 questions consisting of surgical indications, techniques and time to
      return to sports was developed to investigate the preferences of members of the
      TOTBID and the TUSYAD. RESULTS: A total of 147 surgeons answered the
      questionnaire.70% of the respondents were TUSYAD members. 82% of respondents had
      at least five years experience in arthroscopy. Half of the surgeons indicated
      that patient age of 50 was the upper limit for cartilage repair. Irrespective of
      activity level, microfracture (60-67%) was the most frequently used technique for
      lesions smaller 2.5 cm2. In lesions larger than 4 cm2, MACI was the most commonly
      advocated procedure (67%). In patients with high activity levels, mosaicplasty
      was the first choice (69%) for lesions between 2.5 and 4 cm2 in size, followed by
      MACI (27%). CONCLUSION: Patient age, activity level, BMI and lesion size were
      important determinants for the choice of treatment of isolated chondral lesions
      in the knee. These results reflect the choices of experienced knee surgeons in
      the country. Although not widely performed in Turkey and has limited
      reimbursement by the health care system, the first choice for defects over 4 cm2
      was second generation ACI. Third party payers & health reimbursement authorities
      should take into account that large defects require methods which are relatively
      expensive and need high technology. Cross-sectional survey, Level II.

PMID- 27876264
TI  - Intravascular Ultrasound and Near-Infrared Spectroscopic Characterization of Thin
      Cap Fibroatheroma.
AB  - Thin-cap fibroatheromas (TCFAs) are considered precursors for plaque rupture and
      subsequent acute coronary events. We investigated intravascular ultrasound (IVUS)
      and near-infrared spectroscopy (NIRS) characteristics of lesions that were
      histopathologic TCFAs. IVUS, NIRS, and histopathology were performed in 271
      atherosclerotic lesions from 107 fresh coronary arteries from 54 patients at
      necropsy. The plaque burden and remodeling index calculated by IVUS and maximum
      lipid core burden index within any 4-mm segment (maxLCBI4mm) calculated by NIRS
      were compared among each plaque type based on histopathologic classifications but
      focusing on TCFA. Lesions classified as TCFAs had the largest plaque burden, the
      highest remodeling index, and the greatest maxLCBI4mm. Plaque burden >=69% (90%
      sensitivity, 75% specificity, and area under the curve 0.87); remodeling index
      >=1.07 (80% sensitivity, 79% specificity, and area under the curve 0.84); and
      maxLCBI4mm >=323 (80% sensitivity, 85% specificity, and area under the curve
      0.84) predicted a histopathologic TCFA. In conclusion, a large plaque burden and
      a high remodeling index assessed by IVUS and lipid-rich plaque determined by the
      NIRS maxLCBI4mm are useful predictive markers of TCFA.

PMID- 27876265
TI  - A prospective randomized comparison of two distinct allogenic tissue constructs
      for anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Conduct a prospective randomized study to compare clinical outcomes
      of anterior cruciate ligament (ACL) reconstruction using quadrupled hamstring
      tendon (HT) allograft or doubled tibialis anterior (TA) allograft. Limited level
      1 data exist comparing outcomes of different soft tissue allograft constructs for
      ACL reconstruction. We hypothesized no difference would exist in the patient
      reported outcomes (PRO), arthrometric testing, or rate of re-rupture between the
      two constructs. METHODS: Ninety eight subjects undergoing primary ACL
      reconstruction were randomized to HT (n=47) or TA (n=51) allograft. Subjects
      completed validated (PRO) measures pre-operatively, and six months and two years
      post-operatively. Arthrometric testing was performed at six months to assess
      integrity of the reconstruction. RESULTS: Fifty-eight percent of subjects (57/98)
      completed a two-year follow up. Allograft re-tear rates were similar between
      groups (6.2% HT vs. 4.0% TA, respectively, p=1.0). The relative risk of re-tear
      in the HT group was 1.5 compared to the TA group (p=0.7). The TA group improved
      significantly more on the physical portion of the VR-12 (p=0.046) and Lysholm
      score (p=0.014) compared to the HT group. There was no difference in the change
      from baseline for the other PRO scores at two years. CONCLUSIONS: Our data
      indicate no difference in graft failure rate and similar improvement from
      baseline in most PRO scores between treatment groups after two years. Based on
      these findings, TA allograft appears to provide a reliable and satisfactory
      option for patients who elect to undergo allograft ACL reconstruction.

PMID- 27876267
TI  - Open wedge high tibial osteotomy using three-dimensional printed models:
      Experimental analysis using porcine bone.
AB  - BACKGROUND: The purpose of this study was to evaluate the usefulness of three
      dimensional (3D) printed models for open wedge high tibial osteotomy (HTO) in
      porcine bone. METHODS: Computed tomography (CT) images were obtained from 10
      porcine knees and 3D imaging was planned using the 3D-Slicer program. The
      osteotomy line was drawn from the three centimeters below the medial tibial
      plateau to the proximal end of the fibular head. Then the osteotomy gap was
      opened until the mechanical axis line was 62.5% from the medial border along the
      width of the tibial plateau, maintaining the posterior tibial slope angle. The
      wedge-shaped 3D-printed model was designed with the measured angle and osteotomy
      section and was produced by the 3D printer. The open wedge HTO surgery was
      reproduced in porcine bone using the 3D-printed model and the osteotomy site was
      fixed with a plate. Accuracy of osteotomy and posterior tibial slope was
      evaluated after the osteotomy. RESULTS: The mean mechanical axis line on the
      tibial plateau was 61.8+/-1.5% from the medial tibia. There was no statistically
      significant difference (P=0.160). The planned and post-osteotomy correction wedge
      angles were 11.5+/-3.2 degrees  and 11.4+/-3.3 degrees , and the posterior tibial
      slope angle was 11.2+/-2.2 degrees  pre-osteotomy and 11.4+/-2.5 degrees  post
      osteotomy. There were no significant differences (P=0.854 and P=0.429,
      respectively). CONCLUSION: This study showed that good results could be obtained
      in high tibial osteotomy by using 3D printed models of porcine legs.

PMID- 27876266
TI  - Knee arthrodesis by the Ilizarov method in the treatment of total knee
      arthroplasty failure.
AB  - BACKGROUND: Currently, the main indication for knee arthrodesis is septic failure
      of a total knee arthroplasty (TKA). The purpose of this study was to evaluate the
      results of knee arthrodesis by circular external fixation performed in the
      treatment of TKA failure in which revision arthroplasty was not indicated.
      METHODS: The study involved 19 patients who underwent knee arthrodesis by the
      Ilizarov method. Clinical and functional assessments were performed, including
      Knee Society Score (KSS). A postoperative clinical and radiographic evaluation
      was conducted every three months until the end of the treatment. Postoperative
      complications and eventual leg shortening were recorded. RESULTS: KSS results
      showed a significant improvement with respect to the preoperative condition. Of
      the 16 patients in the final follow-up, 15 patients (93.7%) achieved complete
      bone fusion. Major complications occurred in patients treated for septic failure
      of TKA and most occurred in patients over 75years of age; the mean final leg
      shortening was four centimeters. CONCLUSION: In our experience, the Ilizarov
      method is effective for performing a knee arthrodesis in the case of extensive
      bone loss. At the same time, it is possible to correct the associated leg
      deformities or limb length difference. In addition, only the Ilizarov method
      provides a mechanical stimulus for bone formation and improves the quality of the
      bone and of the microcirculation, which enhances the host response against
      infection. Despite these attributes, knee arthrodesis by the Ilizarov method must
      be considered a 'salvage procedure' in cases of severe outcomes from knee surgery
      in which revision arthroplasty is not indicated.

PMID- 27876268
TI  - Vocal changes accompanying the descent of the larynx during ontogeny from
      neonates to adults in male and female goitred gazelles (Gazella subgutturosa).
AB  - The pronouncedly enlarged and descended larynx in male goitred gazelles (Gazella
      subgutturosa), Mongolian gazelles (Procapra gutturosa) and fallow deer (Dama
      dama) represents an interesting parallel to the 'Adam's apple' of human males.
      Goitred gazelles, as humans, are not born with a descended larynx. Therefore the
      sexual dimorphism of larynx size and position develops during ontogeny. In this
      study, the vocal ontogeny of male and female goitred gazelles was investigated
      across five age classes from neonates to adults. The acoustic variables of nasal
      contact calls were measured in 53 (24 male, 29 female) individuals, body mass and
      neck dimensions in 63 (31 male, 32 female) live individuals and nasal vocal tract
      and vocal fold lengths in 26 (16 male, 10 female) anatomical specimens. Call
      fundamental frequency (f0), the acoustic correlate of the ontogenetically
      enlarging larynx, decreased significantly in either sex. Call formants (second,
      third and forth), the acoustic correlates of the ontogenetically elongating vocal
      tract, did not differ significantly between sexes up to early adulthood, but
      clearly diverged in adults. Significant differences between sexes in neck
      circumference at the level of the larynx emerged already at 2-3 months of age,
      whereas body mass, neck circumference at the neck-body transition and the degree
      of larynx descent significantly differed in adults only. We discuss that, in
      contrast to humans, the accelerated enlargement of the larynx in male goitred
      gazelles starts early in ontogeny. A moderate descent of the larynx develops
      equally in both sexes before early adulthood, whereas the additional prominent
      descent of the larynx in males is shifted to late ontogeny. This might avoid
      selective disadvantages of this sexually dimorphic trait on males during their
      period of growth. As has been previously proved for humans, the emergence of the
      strong male-specific descent of the larynx in goitred gazelles may go along with
      the increasing social status and the males' increasing chances of siring
      offspring. Similar to the Adam's apple of human males, this may indicate the
      important role of the enlarged and descended larynx for signaling male status via
      masculine voice.

PMID- 27876269
TI  - A Social Ecology Analysis of Childbirth Among Females Emancipating From Foster
      Care.
AB  - PURPOSE: No research has examined childbirth from a national perspective among
      females emancipating from foster care. The present study fills this gap by: (1)
      documenting the rates of initial and repeat births among females ages 17 and 19
      in a national prospective study and (2) identifying risk and protective factors
      at age 17 that predict childbirth between ages 17 and 19. METHODS: This study
      used data from the National Youth in Transition Database and Adoption and Foster
      Care Analysis and Reporting System to identify risk and protective factors
      associated with childbirth in a national sample of transition-age female youth (N
      = 3,474). RESULTS: The cumulative rate of childbirth by age 19 was 21%, with
      higher rates reported between ages 17 and 19 (17%; n = 602) compared with age 17
      or earlier (9%; n = 313). In logistic regression analysis, black race and
      Hispanic ethnicity, placement with relatives, runaway status, trial home visit
      placement, early emancipation from foster care, and lifetime incarceration
      histories were associated with increased likelihood of childbirth. In contrast,
      school enrollment and employment skills were associated with decreased likelihood
      of childbirth. The multivariate odds of childbirth between ages 17 and 19
      increased 10-fold if youth already had a child by age 17. CONCLUSIONS: Sexual
      health and pregnancy prevention programs should specifically target youths who
      already have children. Increased attention should be paid to adolescents placed
      with biological families and those with histories of criminal involvement.

PMID- 27876270
TI  - A new manufacturing process to remove thrombogenic factors (II, VII, IX, X, and
      XI) from intravenous immunoglobulin gamma preparations.
AB  - Coagulation factors (II, VII, IX, X, and particularly XIa) remaining in high
      concentrations in intravenous immunoglobulin (IVIG) preparations can form
      thrombi, causing thromboembolic events, and in serious cases, result in death.
      Therefore, manufacturers of biological products must investigate the ability of
      their production processes to remove procoagulant activities. Previously, we were
      able to remove coagulation factors II, VII, IX, and X from our IVIG preparation
      through ethanol precipitation, but factor XIa, which plays an important role in
      thrombosis, remained in the intermediate products. Here, we used a
      chromatographic process using a new resin that binds with high capacity to IgG
      and removes procoagulant activities. The procoagulant activities were reduced to
      low levels as determined by the thrombin generation assay: <1.56 mIU/mL,
      chromogenic FXIa assay: <0.16 mIU/mL, non-activated partial thromboplastin time
      (NaPTT): >250 s, FXI/FXIa ELISA: <0.31 ng/mL. Even after spiking with FXIa at a
      concentration 32.5 times higher than the concentration in normal specimens, the
      procoagulant activities were below the detection limit (<0.31 ng/mL). These
      results demonstrate the ability of our manufacturing process to remove
      procoagulant activities to below the detection limit (except by NaPTT),
      suggesting a reduced risk of thromboembolic events that maybe potentially caused
      by our IVIG preparation.

PMID- 27876271
TI  - HIV Infection Is Independently Associated with Increased CT Scan Lung Density.
AB  - RATIONALE AND OBJECTIVES: Noninfectious pulmonary complications are common among
      HIV-infected individuals and may be detected early by quantitative computed
      tomography (CT) scanning. The association of HIV disease markers with CT lung
      density measurement remains poorly understood. MATERIALS AND METHODS: One hundred
      twenty-five participants free of spirometry-defined lung disease were recruited
      from a longitudinal cohort study of HIV-infected and HIV-uninfected individuals
      to undergo standardized CT scan of the chest. Parenchymal density for the entire
      lung volume was calculated using computerized software. Qualitative assessment of
      CT scans was conducted by two radiologists masked to HIV status. Linear
      regression models were developed to determine the independent association of
      markers of HIV infection on inspiratory scan mean lung density (MLD). RESULTS:
      HIV-infected participants had a significantly higher MLD (denser lung) compared
      to HIV-uninfected participants (-815 Hounsfield unit [HU] vs -837 HU; P = 0.002).
      After adjusting for relevant covariates, HIV infection was independently
      associated with 19.9 HU higher MLD (95% CI 6.04 to 33.7 HU; P = 0.005). In
      qualitative assessment, only ground glass attenuation and cysts were noted more
      commonly among HIV-infected individuals compared to HIV-uninfected individuals
      (34% vs 17% [P = 0.045] and 27% vs 10% [P = 0.03], respectively). No qualitative
      radiographic abnormalities attenuated the association between HIV infection and
      increased MLD. CONCLUSIONS: HIV infection is independently associated with
      increased lung density. Although qualitative CT abnormalities were common in this
      cohort, only ground glass attenuation and cysts were noted more frequently in HIV
      infected participants, suggesting that the increased lung density observed among
      HIV-infected individuals may be associated with subclinical inflammatory lung
      changes.

PMID- 27876272
TI  - Evaluation of Rib Fractures on a Single-in-plane Image Reformation of the Rib
      Cage in CT Examinations.
AB  - RATIONALE AND OBJECTIVES: This study aimed to evaluate the diagnostic performance
      of using a reformatted single-in-plane image reformation of the rib cage for the
      detection of rib fractures in computed tomography (CT) examinations, employing
      different levels of radiological experience. MATERIALS AND METHODS: We
      retrospectively evaluated 10 consecutive patients with and 10 patients without
      rib fractures, whose CT scans were reformatted to a single-in-plane image
      reformation of the rib cage. Eight readers (two radiologists, two residents in
      radiology, and four interns) independently evaluated the images for the presence
      of rib fractures using a reformatted single-in-plane image and a multi-planar
      image reformation. The time limit was 30 seconds for each read. A consensus of
      two radiologist readings was considered as the reference standard. Diagnostic
      performance (sensitivity, specificity, positive predictive value [PPV], and
      negative predictive value [NPV]) was assessed and evaluated per rib and per
      location (anterior, lateral, posterior). To determine the time limit, we
      prospectively analyzed the average time it took radiologists to assess the rib
      cage, in a bone window setting, in 50 routine CT examinations. McNemar test was
      used to compare the diagnostic performances. RESULTS: Single image reformation
      was successful in all 20 patients. The sensitivity, specificity, PPV, and NPV for
      the detection of rib fractures using the conventional multi-planar read were
      77.5%, 99.2%, 89.9%, and 98.0% for radiologists; 46.3%, 99.7%, 92.5%, and 95.3%
      for residents; and 29.4%, 99.4%, 82.5%, and 93.9% for interns, respectively.
      Sensitivity, PPV, and NPV increased across all three groups of experience, using
      the reformatted single-in-plane image of the rib cage (radiologists: 85.0%,
      98.6%, and 98.7%; residents: 80.0%, 92.8%, and 98.2%; interns: 66.9%, 89.9%, and
      97.1%), whereas specificity did not change significantly (99.9%, 99.4%, and
      99.3%). The diagnostic performance of the interns and residents was significantly
      better when evaluating the single-in-plane image reformations (P < .01). The
      diagnostic performance of the radiologists was better when evaluating the single
      in-plane image reformations; however, there was no significant difference
      (statistical power: 0.32). CONCLUSIONS: The diagnostic performance for the
      detection of rib fractures, using CT images that have been reformatted to a
      single-in-plane image, improves for readers from different educational levels
      when the evaluation time is restricted to 30 seconds or less.

PMID- 27876273
TI  - The MacArthur Competence Assessment Tools for assessing decision-making capacity
      in schizophrenia: A meta-analysis.
AB  - OBJECTIVE: This meta-analysis aimed to examine the decisional capacity measured
      by the MacArthur Competence Assessment Tools (MacCAT) in schizophrenia. METHOD:
      English (PubMed, PsycINFO, Embase, Cochrane Library databases and the Cochrane
      Controlled Trials Register) and Chinese (Wan Fang Database and Chinese National
      Knowledge Infrastructure) databases were systematically and independently
      searched from 1995 until August 1, 2016. Weighted and standardized mean
      differences were calculated. The random effects model was used in all cases.
      RESULTS: Altogether 10 studies were identified, with 7 studies using the
      MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and 3
      studies using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T).
      The meta-analysis showed that there was significant impairment in decision-making
      capacity in schizophrenia patients compared to the healthy control group in terms
      of Understanding (SMD=-0.81, 95% CI: -1.06 to -0.56, P<0.001), Reasoning (SMD=
      0.57, 95% CI: -0.80 to -0.34, P<0.001), Appreciation (SMD=-0.87, 95% CI: -1.20 to
      -0.53, P<0.001), and Expression a choice (SMD=-0.24, 95% CI: -0.43 to -0.05,
      P=0.01). CONCLUSION: Compared to the control group, schizophrenia patients are
      more likely to have impaired decision-making capacity in clinical research and
      treatment as measured by the MacCAT instruments. Researchers and clinicians need
      to consider the impaired decisional capacity in schizophrenia patients providing
      informed consent.

PMID- 27876274
TI  - Are there any ways around the exposure-limiting nephrotoxicity of the polymyxins?
AB  - The polymyxins (colistin and polymyxin B) have emerged over the past 20 years as
      essential antibacterial agents that often are the only remaining active class
      against troublesome multidrug-resistant Gram-negative bacilli such as carbapenem
      resistant Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacteriaceae.
      The utility of this class is limited by its dose-dependent nephrotoxicity, which
      can occur in more than one-half of patients receiving therapy with either agent.
      Strategies are urgently needed to optimise the use of this class of agents to
      ensure optimal activity while minimising the treatment-limiting nephrotoxicity.
      This review will focus on risk factors for polymyxin-associated nephrotoxicity,
      potential strategies for limiting this exposure-dependent toxicity and, finally,
      unknowns and future research directions pertinent to this topic.

PMID- 27876275
TI  - Development of Leishmania donovani stably expressing DsRed for flow cytometry
      based drug screening using chalcone thiazolyl-hydrazone as a new antileishmanial
      target.
AB  - Green fluorescent protein produces significant fluorescence and is extremely
      stable, however its excitation maximum is close to the ultraviolet range and thus
      can damage living cells. Hence, Leishmania donovani stably expressing DsRed were
      developed and their suitability for flow cytometry-based antileishmanial
      screening was assessed by evaluating the efficacies of standard drugs as well as
      newly synthesised chalcone thiazolyl-hydrazone compounds. The DsRed gene was
      successfully integrated at the 18S rRNA locus of L. donovani and transfectants
      (LdDsRed) were selected using hygromycin B. Enhanced expression of DsRed and a
      high level of infectivity to J774A.1 macrophages were achieved, which was
      confirmed by fluorescence microscopy and flow cytometry. Furthermore, these
      LdDsRed transfectants were utilised for development of an in vitro screening
      assay using the standard antileishmanial drugs miltefosine, amphotericin B,
      pentamidine and paromomycin. The response of transfectants to standard drugs
      correlated well with previous reports. Subsequently, the suitability of this
      system was further assessed by screening a series of 18 newly synthesised
      chalcone thiazolyl-hydrazone compounds in vitro for their antileishmanial
      activity, wherein 8 compounds showed moderate antileishmanial activity. The most
      active compound 5g, with ca. 73% splenic parasite reduction, exerted its activity
      via generating nitric oxide and reactive oxygen species and inducing apoptosis in
      LdDsRed-infected macrophages. Thus, these observations established the
      applicability of LdDsRed transfectants for flow cytometry-based antileishmanial
      screening. Further efforts aimed at establishing a high-throughput screening
      assay and determining the in vivo screening of potential antileishmanial leads
      are required.

PMID- 27876276
TI  - Piperacillin/tazobactam as an alternative antibiotic therapy to carbapenems in
      the treatment of urinary tract infections due to extended-spectrum beta-lactamase
      producing Enterobacteriaceae: an in silico pharmacokinetic study.
AB  - Piperacillin/tazobactam (TZP) as an alternative treatment to carbapenems for
      infections involving extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae (ESBL-PE) remains debated. In this study, the probabilities of
      pharmacodynamic (PD) target attainment with different TZP regimens in ESBL
      producing Escherichia coli (ESBL-Ec) and Klebsiella pneumoniae (ESBL-Kp) were
      evaluated in the context of pyelonephritis. Minimum inhibitory concentrations
      (MICs) of 144 ESBL-Ec and 111 ESBL-Kp from pyelonephritis were measured, and two
      previously published population pharmacokinetic models were used to determine by
      Monte Carlo simulation the probabilities of reaching two PD targets (50%fT>MIC
      and 100%fT>MIC) with TZP doses of 4 g three times daily and 4.5 g four times
      daily given as short (1 h) or prolonged (4 h) infusions or as 12-18 g/day
      continuous infusions. Only MICs of the 133 ESBL-Ec and 74 ESBL-Kp strains
      susceptible to TZP according to inhibition zone diameter were considered for the
      simulations. Results were similar with the two models, and only prolonged and
      continuous infusions allowed to reach 50%fT>MIC with a probability of >90%
      irrespective of bacterial species. Continuous infusion and prolonged infusion
      combined with the maximum dosage were the only condition allowing to achieve
      100%fT>MIC with a probability of >70% with this population of ESBL-Ec. A
      probability of >90% to reach 100%fT>MIC with ESBL-Kp could be obtained only with
      the 18 g/day continuous-infusion regimen. TZP may be used for treatment for mild
      pyelonephritis involving susceptible ESBL-Ec provided that administration
      modalities are optimised. Conversely, for ESBL-Kp the risk of treatment failure
      may be higher, supporting the use of continuous infusion.

PMID- 27876277
TI  - The Ascent of Man and the Politics of Humanity's Evolutionary Future.
AB  - Throughout the twentieth century, contemporary understandings of evolutionary
      theory were tightly linked to visions of the future freighted with moral
      consequence. This essay traces the origins and legacy of this scientific
      commitment to a universal family of man in postwar evolutionary theory, and
      elaborates how evolutionary scientists sought to reframe the politics of human
      evolution by claiming that the principles governing the physical past of humanity
      differed fundamentally from those that would matter in the coming decades,
      centuries, or even millennia. Education and public engagement embodied the moral
      importance of actively participating in the creation of that better, future
      world.

PMID- 27876278
TI  - Event-based finite-time state estimation for Markovian jump systems with
      quantizations and randomly occurring nonlinear perturbations.
AB  - This paper is concerned with finite-time state estimation for Markovian jump
      systems with quantizations and randomly occurring nonlinearities under event
      triggered scheme. The event triggered scheme and the quantization effects are
      used to reduce the data transmission and ease the network bandwidth burden. The
      randomly occurring nonlinearities are taken into account, which are governed by a
      Bernoulli distributed stochastic sequence. Based on stochastic analysis and
      linear matrix inequality techniques, sufficient conditions of stochastic finite
      time boundedness and stochastic Hinfinity finite-time boundedness are firstly
      derived for the existence of the desired estimator. Then, the explicit expression
      of the gain of the desired estimator are developed in terms of a set of linear
      matrix inequalities. Finally, a numerical example is employed to demonstrate the
      usefulness of the theoretical results.

PMID- 27876279
TI  - Non-fragile sampled-data robust synchronization of uncertain delayed chaotic
      Lurie systems with randomly occurring controller gain fluctuation.
AB  - This paper proposes a new non-fragile stochastic control method to investigate
      the robust sampled-data synchronization problem for uncertain chaotic Lurie
      systems (CLSs) with time-varying delays. The controller gain fluctuation and time
      varying uncertain parameters are supposed to be random and satisfy certain
      Bernoulli distributed white noise sequences. Moreover, by choosing an appropriate
      Lyapunov-Krasovskii functional (LKF), which takes full advantage of the available
      information about the actual sampling pattern and the nonlinear condition, a
      novel synchronization criterion is developed for analyzing the corresponding
      synchronization error system. Furthermore, based on the most powerful free-matrix
      based integral inequality (FMBII), the desired non-fragile sampled-data estimator
      controller is obtained in terms of the solution of linear matrix inequalities.
      Finally, three numerical simulation examples of Chua's circuit and neural network
      are provided to show the effectiveness and superiorities of the proposed
      theoretical results.

PMID- 27876280
TI  - Validity and intra-rater reliability of MyJump app on iPhone 6s in jump
      performance.
AB  - OBJECTIVES: Smartphone applications are increasingly used by researchers,
      coaches, athletes and clinicians. The aim of this study was to examine the
      concurrent validity and intra-rater reliability of the smartphone-based
      application, MyJump, against laboratory-based force plate measurements. DESIGN:
      Cross sectional study. METHODS: Participants completed counter-movement jumps
      (CMJ) (n=29) and 30cm drop jumps (DJ) (n=27) on a force plate which were
      simultaneously recorded using MyJump. To assess concurrent validity, jump height,
      derived from flight time acquired from each device, was compared for each jump
      type. Intra-rater reliability was determined by replicating data analysis of
      MyJump recordings on two occasions separated by seven days. RESULTS: CMJ and DJ
      heights derived from MyJump showed excellent agreement with the force plate (ICC
      values range from 0.991 for CMJ to 0.993) However mean DJ height from the force
      plate was significantly higher than MyJump (mean difference: 0.87cm, 95% CI: 0.69
      1.04cm). Intra-rater reliability of MyJump for both CMJ and DJ was almost perfect
      (ICC values range from 0.997 for CMJ to 0.998 for DJ); however, mean CMJ and DJ
      jump height for Day 1 was significantly higher than Day 2 (CMJ: 0.43cm, 95% CI:
      0.23-0.62cm); (DJ: 0.38cm, 95% CI: 0.23-0.53cm). CONCLUSION: The present study
      finds MyJump to be a valid and highly reliable tool for researchers, coaches,
      athletes and clinicians; however, systematic bias should be considered when
      comparing MyJump outputs to other testing devices.

PMID- 27876281
TI  - Post-transplant surveillance for acute rejection and allograft vasculopathy by
      echocardiography: Usefulness of myocardial velocity and deformation imaging.
AB  - Diagnosing and monitoring acute rejection (AR) and cardiac allograft vasculopathy
      (CAV) is essential for graft and transplant patient survival and, consequently, a
      major objective for heart transplant patient surveillance. Because functionally
      relevant CAV can arise and progress without clinical symptoms and sub-clinical
      ARs can facilitate the development of CAV, standard surveillance of AR and CAV
      includes routine endomyocardial biopsy (EMB) and coronary angiography (CA)
      screenings at pre-defined time intervals. However, these invasive screenings
      (distressing and risky for the patients) cannot solely diagnose all sub-clinical
      AR episodes and also not always detect coronary stenoses before a clinical event.
      Additional close-meshed, non-invasive AR and CAV surveillance strategies are
      therefore mandatory. After the introduction of tissue Doppler imaging (TDI) and
      strain imaging for myocardial wall motion and deformation analysis,
      echocardiography became particularly promising for that purpose. Allowing
      quantification of minor myocardial dysfunction not detectable by standard
      echocardiography, TDI and strain imaging can reveal sub-clinical AR. Thus, these
      approaches can be a valuable supplement to EMB, enabling more efficient AR
      monitoring with fewer EMBs (only diagnostic EMBs) instead of unnecessary and
      distressing routine EMB screenings. Their use can also improve therapeutic
      decisions and monitoring of myocardial function during anti-rejection therapy.
      Myocardial velocity and deformation imaging is also suited to early detection of
      myocardial dysfunction induced by CAV and may be useful for prognostic evaluation
      and timing of CAs, with an aim of reducing the number of routine CA screenings.
      However, further studies are necessary before specific recommendations for the
      use of TDI and strain imaging for CAV surveillance become possible.

PMID- 27876282
TI  - To use or not to use? Amiodarone before heart transplantation.
AB  - BACKGROUND: Amiodarone frequently is used in patients with heart failure.
      Concerns still exist about possible complications related to its lingering effect
      during and after heart transplantation. METHODS: We selected all consecutive
      patients who received a heart transplant at our institution between January 2004
      and December 2015 (n = 220) and compared the peri- and postoperative outcomes of
      patients who were taking amiodarone for at least 120 days before heart transplant
      (n = 127) with patients who did not take amiodarone prior to heart transplant (n
      = 93). RESULTS: Compared with patients with no amiodarone use prior to
      transplant, those who had used amiodarone were similar in age, body mass index,
      sex, cause of cardiomyopathy, prevalence of diabetes, hypertension, presence of
      defibrillator, and had similar donor ischemic times during transplant (all P >
      .05). Median operative time, aortic cross clamp time, mechanical ventilation and
      median hospital duration of stay did not differ between the 2 groups (P > .05).
      Patients exposed to amiodarone had fewer cellular rejections (5% vs 20%; P =
      .001) but more primary graft dysfunction (4% vs 0%; P = .025) and post-transplant
      pneumonia (P = .047) compared with patients not taking amiodarone prior to
      transplant. Both groups had similar rate of atrial fibrillation, 30-day
      readmission, and 30-day mortality (P > .05). Even though 1-year survival was not
      affected by amiodarone use (P = .51), long-term (5-year) survival was
      significantly less in patients exposed to amiodarone (P = .03). CONCLUSION:
      Amiodarone use did not affect the incidence of atrial fibrillation nor 30-day and
      1-year survival post-transplantation. Nevertheless, post-transplant pulmonary
      complications were significantly greater and 5-year survival was less among
      patients treated with amiodarone prior to transplant.

PMID- 27876283
TI  - Importance of trabecular anisotropy in finite element predictions of patellar
      strain after Total Knee Arthroplasty.
AB  - Patellar fracture and anterior knee pain remain major complications after Total
      Knee Arthroplasty (TKA). Patient-specific finite element (FE) models should help
      improve understanding of these complications through estimation of joint and bone
      mechanics. However, sensitivity of predictions on modeling techniques and
      approaches is not fully investigated. In particular, the importance of patellar
      bone anisotropy, usually omitted in FE models, on strain prediction is still
      unknown. The objective of this study was thus to estimate the influence of
      modeling patellar trabecular anisotropy on prediction of patellar strain in TKA
      models. We compared FE-derived strain predictions with isotopic and anisotropic
      material properties using 17 validated FE models of the patella after TKA. We
      considered both non-resurfaced and resurfaced patellae, in a load-bearing TKA
      joint. We evaluated and compared the bone volume above a strain threshold and, in
      addition, estimated if the difference in isotopic and anisotropic predictions was
      consistent between patellae of different average bone volume fraction. Compared
      to the anisotropic reference, the isotropic prediction of strained volume was
      3.7+/-1.8 times higher for non-resurfaced patellae and 1.5+/-0.4 times for
      resurfaced patellae. This difference was higher for patellae with lower average
      bone volume fraction. This study indicates that strain predictions acquired via
      isotropic patellar FE models should be interpreted with caution, especially when
      patellae of different average bone volume fraction are compared.

PMID- 27876284
TI  - Calculation of tumour and normal tissue biological effective dose in 90Y liver
      radioembolization with different dosimetric methods.
AB  - PURPOSE: Radioembolization with 90Y microspheres is an effective treatment for
      unresectable liver tumours. Two types of microspheres are available: resin (SIR
      Spheres(r)) and glass (Theraspheres(r)). The aim of this study is to compare
      biological effective dose (BED) values obtained with three different dosimetric
      methods. METHODS: 29 HCC patients were included in this study: 15 were treated
      with resin(mean injected activity 1.5GBq, range 0.8-2.7GBq) and 14 with glass
      microspheres (2.6GBq, range 1.3-4.1GBq). Average doses to tumours and normal
      liver tissues were calculated with AAPM, multi-compartmental MIRD and Voxel-based
      methods and consequently the BED values were obtained. Planar images were used
      for the AAPM method: 99mTc-MAA SPECT-CT attenuation and scatter corrected images
      (resin) and 99m Tc-MAA SPECT attenuation corrected (glass) were employed for the
      other two methods. RESULTS: Regardless of type of microspheres, both for tumours
      and normal liver tissues, no significant statistical differences were found
      between MIRD and Voxel for both doses and BED values. Conversely AAPM gave
      discordant results with respect to the other two methods (Mann-Whitney p
      values?0.01). For resin spheres the calculated tumour-to-normal tissue ratios on
      planar images were on average 14 times greater than those obtained on SPECT-CT
      images, while they were 4 times greater on glass. A linear correlation was
      observed between MIRD and Voxel BEDs. CONCLUSIONS: The AAPM method appears to be
      less precise for absorbed dose and BED estimation, while MIRD and voxel based
      dosimetry are more confident each other.

PMID- 27876285
TI  - Zero field PDD and TMR data for unflattened beams in conventional linacs: A tool
      for independent dose calculations.
AB  - PURPOSE: To investigate the applicability of the formalism described in BJR
      supplement n.25 for Flattening Filter Free (FFF) beams in determining the zero
      field tissue maximum ratio (TMR) for an independent calculation method of
      Percentage Depth Doses (PDDs) and relative dose factors (RDFs) at different
      experimental setups. METHODS: Experimental PDDs for field size from 40*40cm2 to
      2*2cm2 with Source Surface Distance (SSD) 100cm were acquired. The normalized
      peak scatter factor for each square field was obtained by fitting experimental
      RDFs in water and collimator factors (CFs) in air. Maximum log-likelihood methods
      were used to extract fit parameters in competing models and the Bayesian
      Information Criterion was used to select the best one. In different experimental
      setups additional RDFs and TPR1020s for field sizes other than reference field
      were measured and Monte Carlo simulations of PDDs at SSD 80cm were carried out to
      validate the results. PDD agreements were evaluated by gamma analysis. RESULTS:
      The BJR formalism allowed to predict the PDDs obtained with MC within 2%/2mm at
      SSD 80cm from 100% down to 50% of the maximum dose. The agreement between
      experimental TPR1020s and RDFs values at SSD=90cm and BJR calculations were
      within 1% for field sizes greater than 5*5cm2 while it was within 3% for fields
      down to 2*2cm2. CONCLUSIONS: BJR formalism can be used for FFF beams to predict
      PDD and RDF at different SSDs and can be used for independent MU calculations.

PMID- 27876286
TI  - Clinical Trials in a Dish.
AB  - Clinical trials 'in a dish' involve testing medical therapies for safety or
      effectiveness in the laboratory with human tissue. This has become possible owing
      to recent biotechnology advances including induced pluripotent stem cells, organs
      on-a-chip, and whole-genome sequencing. We provide here an overview of the
      landscape and highlight steps the FDA is taking to advance the science of
      clinical trials in a dish and to support the development and validation of new
      regulatory paradigms to assess drug safety using these new technologies.

PMID- 27876288
TI  - Trends, prospects and deprivation index of disability in India: Evidences from
      census 2001 and 2011.
AB  - BACKGROUND: Since the dawn of civilization, disabilities have existed in various
      dimensions of human life. World Health Organization (WHO) defines disability as
      an umbrella term, covering impairments, activity limitations, and participation
      restrictions. Globally, approximately 1 billion people have some form of
      disability, and approximately 20% have significant functioning impairments.
      OBJECTIVE: This study aims to estimate the level, trends and prospects of
      disability in 640 districts of India. Data for the present study has been taken
      from Census of India, 2001 and 2011. METHODS: A Disability Index was calculated
      at the district level, and state level indexing was done using the Disability
      Deprivation Index. The population for the year 2021 was projected using the
      exponential growth rate method. The Disability Deprivation Index was calculated
      using child labor, adult unemployment, illiteracy, and the ratio of beggars in
      the disabled population. RESULTS: The study reveals that the proportion of the
      disabled population in India was 2.10% in 2001, which increased to 2.21% in 2011.
      According to the Disability Deprivation Index, Maharashtra was the best
      performing state in 2011. There were 4.90 million new cases of disability in
      India during 2001-11, out of which 1.52 million cases belonged to non-congenital
      disability. CONCLUSIONS: There is a rise in the disabled population in India,
      which needs special attention. The working status of the disabled is gloomy. The
      majority of the disabled people are non-working and need adequate rehabilitation
      measures that would facilitate employment.

PMID- 27876287
TI  - Mid-term Outcomes of Common Congenital Heart Defects Corrected Through a Right
      Subaxillary Thoracotomy.
AB  - OBJECTIVE: To evaluate the mid-term outcomes of the correction of various
      congenital heart defects through a right subaxillary thoracotomy. METHODS:
      Between June 2004 and April 2014, all eligible patients were those with a common
      congenital heart defect corrected via an approach through a right subaxillary
      thoracotomy. There were 836 patients (male 417, female 419; median age, 3.5
      years; median weight 13.6kg) with ventricular septal defect (VSD) closure (523
      patients), atrial septal defect (ASD) closure (235 patients), partial
      atrioventricular canal (PAVC) correction (55 patients), mild tetralogy of Fallot
      (TOF) (23 patients). Additional procedures involved tricuspid valvuloplasty (TVP)
      (68 patients), repair of partial anomalous pulmonary venous connection (PAPVC)
      (54 patients), mitral annuloplasty (42 patients), closure of patent ductus
      arteriosus (PDA) (35 patients), correction of cor triatriatum (eight patients).
      The median cardiopulmonary bypass (CPB) and aortic cross-clamp times were 67
      (28~217) and 23 (3~116) min, respectively. RESULTS: The procedures were performed
      successfully in all patients, and no in-hospital mortality occurred. There was no
      need for conversion to another approach in all procedures. The main complications
      involved arrhythmia in 21 patients, atelectasis in 18, pneumothorax in 17,
      subcutaneous emphysema in 15, pulmonary infection in 14, low cardiac output
      syndrome in eight, transient cerebral dysfunction in two. The patients were all
      in excellent condition after a mean follow-up of 34 months. The cardiac defect
      was repaired with no residual defect in 820 patients and with trivial to mild
      residual defect in 16 patients (10 with small VSD residual shunt, four with mild
      mitral regurgitation, two with mild residual right ventricular outflow tract
      obstruction). The incision healed properly in all, and the thorax showed no
      deformity. CONCLUSIONS: Right subaxillary thoracotomy, providing an advantageous
      alternative, can be performed with favourable cosmetic and satisfactory clinical
      results for the correction of a wide range of common congenital heart defects.

PMID- 27876289
TI  - Development of an efficient anaerobic co-digestion process for garbage, excreta,
      and septic tank sludge to create a resource recycling-oriented society.
AB  - In order to develop a resource recycling-oriented society, an efficient anaerobic
      co-digestion process for garbage, excreta and septic tank sludge was studied
      based on the quantity of each biomass waste type discharged in Ooki machi, Japan.
      The anaerobic digestion characteristics of garbage, excreta and 5-fold condensed
      septic tank sludge (hereafter called condensed sludge) were determined
      separately. In single-stage mesophilic digestion, the excreta with lower C/N
      ratios yielded lower biogas volumes and accumulated higher volumes of volatile
      fatty acid (VFA). On the other hand, garbage allowed for a significantly larger
      volatile total solid (VTS) digestion efficiency as well as biogas yield by
      thermophilic digestion. Thus, a two-stage anaerobic co-digestion process
      consisting of thermophilic liquefaction and mesophilic digestion phases was
      proposed. In the thermophilic liquefaction of mixed condensed sludge and
      household garbage (wet mass ratio of 2.2:1), a maximum VTS loading rate of
      24g/L/d was achieved. In the mesophilic digestion of mixed liquefied material and
      excreta (wet mass ratio of 1:1), biogas yield reached approximately 570ml/g-VTS
      fed with a methane content of 55% at a VTS loading rate of 1.0g/L/d. The
      performance of the two-stage process was evaluated by comparing it with a single
      stage process in which biomass wastes were treated separately. Biogas production
      by the two-stage process was found to increase by approximately 22.9%. These
      results demonstrate the effectiveness of a two-stage anaerobic co-digestion
      process in enhancement of biogas production.

PMID- 27876290
TI  - Response of mixed methanotrophic consortia to different methane to oxygen ratios.
AB  - Methane (CH4) and oxygen (air) concentrations affect the CH4 oxidation capacity
      (MOC) and mixed methanotrophic community structures in compost (fresh) and
      landfill (age old) top cover soils. A change in the mixed methanotrophic
      community structure in response has implications for landfill CH4 bio-filter
      remediation and possible bio-product outcomes (i.e., fatty acid methyl esters
      (FAME) content and profiles and polyhydroxybutyrate (PHB) contents). Therefore
      the study aimed to evaluate the effect of variable CH4 to oxygen ratios (10-50%
      CH4 in air) on mixed methanotrophic community structures enriched from landfill
      top cover (LB) and compost soils (CB) and to quantify flow on impacts on MOC,
      total FAME contents and profiles, and PHB accumulation. A stable consortium
      developed achieving average MOCs of 3.0+/-0.12, 4.1+/-0.26, 6.9+/-0.7, 7.6+/-1.3
      and 9.2+/-1.2mgCH4g-1DWbiomassh-1 in LB and 2.9+/-0.04, 5.05+/-0.32, 6.7+/-0.31,
      7.9+/-0.61 and 8.6+/-0.48mgCH4g-1DWbiomassh-1 in CB for a 20day cultivation
      period at 10, 20, 30, 40 and 50% CH4, respectively. CB at 10% CH4 had a maximal
      FAME content of 40.5+/-0.8mgFAMEg-1DWbiomass, while maximal PHB contents (25mgg
      1DWbiomass) was observed at 40% CH4 in LB. Despite variable CH4/O2 ratios, the
      mixed methanotrophic community structures in both LB and CB were relatively
      stable, dominated by Methylosarcina sp., and Chryseobacterium, suggesting that a
      resilient consortium had formed which can now be tested in bio-filter operations
      for CH4 mitigations in landfills.

PMID- 27876291
TI  - Monetising the impacts of waste incinerators sited on brownfield land using the
      hedonic pricing method.
AB  - In England and Wales planning regulations require local governments to treat
      waste near its source. This policy principle alongside regional self-sufficiency
      and the logistical advantages of minimising distances for waste treatment mean
      that energy from waste incinerators have been built close to, or even within
      urban conurbations. There is a clear policy and research need to balance the
      benefits of energy production from waste incinerators against the negative
      externalities experienced by local residents. However, the monetary costs of
      nuisance emissions from incinerators are not immediately apparent. This study
      uses the Hedonic Pricing Method to estimate the monetary value of impacts
      associated with three incinerators in England. Once operational, the impact of
      the incinerators on local house prices ranged from approximately 0.4% to 1.3% of
      the mean house price for the respective areas. Each of the incinerators studied
      had been sited on previously industrialised land to minimise overall impact. To
      an extent this was achieved and results support the effectiveness of spatial
      planning strategies to reduce the impact on residents. However, negative impacts
      occurred in areas further afield from the incinerator, suggesting that more can
      be done to minimise the impacts of incinerators. The results also suggest that in
      some case the incinerator increased the value of houses within a specified
      distance of incinerators under specific circumstances, which requires further
      investigation.

PMID- 27876293
TI  - Foreword.

PMID- 27876292
TI  - Reprint of: The new approach to classification: Rethinking cognition and behavior
      in epilepsy.
AB  - There has been considerable debate surrounding the benefits and drawbacks of the
      new approach to classifying the epilepsies released by the ILAE Commission on
      Classification and Terminology (2005-2009). This new approach has significant
      implications for the way we conceptualize and assess cognition and behavior in
      epilepsy; however, as yet, there has been limited discussion of these issues in
      the field. The purpose of this Targeted Review is to spark this discussion by
      encouraging researchers and clinicians to think about the changes that the new
      approach may bring. These may include (i) reframing the way we think about the
      comorbidities of epilepsy, (ii) more precisely characterizing the cognitive and
      behavioral phenotypes of electroclinical syndromes, (iii) more carefully mapping
      the longitudinal trajectory of cognitive and behavioral features relative to the
      timing of seizures, and (iv) considering the links between cognitive, behavioral,
      and neurological phenotypes in the new classification scheme. It is hoped that
      such changes will aid translation of the advances in cognitive and behavioral
      neuroscience into routine clinical practice by providing purer markers of disease
      and more targeted treatments. A Special Issue canvassing such issues will be
      forthcoming that will consider current knowledge of the cognitive and behavioral
      features of the epilepsies from the view of the new classification scheme.

PMID- 27876294
TI  - Reprint of: The new approach to epilepsy classification: Cognition and behavior
      in adult epilepsy syndromes.
AB  - The revised terminology and concepts for the organization of seizures and
      epilepsy proposed by the ILAE Commission on Classification and Terminology in
      2010 allows for a number of new opportunities in the study of cognition and
      behavior in adults. This review examines the literature that has looked for
      behavioral and cognitive correlates of the newly recognized genetic epilepsies in
      adults. While some studies report clear cognitive phenotypes associated with
      specific genetic mutations in adults with epilepsy, others report remarkable
      clinical heterogeneity. In the second part of this review, we discuss some of the
      factors that may influence the findings in this literature. Cognitive function is
      the product of both genetic and environmental influences. Neuropsychological
      phenotypes under direct genetic influence may be wider and more subtle than
      specific deficits within discreet cognitive domains and may be reflected in
      broader, multidimensional measures of cognitive function than those tapped by
      scores on standardized tests of function. Future studies must be carefully
      designed to reflect these factors. It is also imperative that studies with
      negative findings are assigned as much value as those with positive results and
      published accordingly. This article is part of a Special Issue titled "The new
      approach to classification: Rethinking cognition and behavior in epilepsy".

PMID- 27876295
TI  - [Doctor Pio Baroja y Nessi, an intellectual with a fragility syndrome].

PMID- 27876296
TI  - Pathogenic features of clinically significant coagulase-negative staphylococci in
      hospital and community infections in Benin.
AB  - In West Africa, very little consideration has been given to coagulase negative
      Staphylococci (CNS). Herein, we describe the features contributing to the
      pathogenicity of 99 clinically-significant independent CNS isolates associated
      with infections encountered at the National Teaching Hospital Center of Cotonou
      (Benin). The pathogenic potentials of nosocomial strains were compared with
      community strains. S. haemolyticus (44%), S. epidermidis (22%) and S. hominis
      (7%) were the most frequently isolated while bacteremia (66.7%) and urinary tract
      infections (24.2%) were the most commonly encountered infections. Most strains
      were resistant to multiple antibiotics, including penicillin (92%), fosfomycin
      (81%), methicillin (74%) and trimethoprim-sulfamethoxazole (72%). The most
      frequently isolated species were also the most frequently resistant to
      methicillin: S. hominis (100%), S. haemolyticus (93%) and S. epidermidis (67%).
      Screening of toxic functions or toxin presence revealed hemolytic potential in
      25% of strains in over 50% of human erythrocytes in 1h. Twenty-six percent of
      strains exhibited protease activity with low (5%), moderate (10%) and high
      activity (11%), while 25% of strains displayed esterase activity. Three percent
      of strain supernatants were able to lyse 100% of human polymorphonuclear cells
      after 30min. Polymerase chain reaction and latex agglutination methods revealed
      staphylococcal enterotoxin C gene expression in 9% of S. epidermidis. A majority
      of hospital-associated CNS strains (68%) had at least one important virulence
      feature, compared with only 32% for community-acquired strains. The present
      investigation confirms that these microorganisms can be virulent, at least in
      some individual cases, possibly through genetic transfer from S. aureus.

PMID- 27876297
TI  - Host transcriptomic responses to pneumonic plague reveal that Yersinia pestis
      inhibits both the initial adaptive and innate immune responses in mice.
AB  - Pneumonic plague is the most deadly form of infection caused by Yersinia pestis
      and can progress extremely fast. However, our understanding on the host
      transcriptomic response to pneumonic plague is insufficient. Here, we used RNA
      sequencing technology to analyze transcriptomic responses in mice infected with
      fully virulent strain 201 or EV76, a live attenuated vaccine strain lacking the
      pigmentation locus. Approximately 600 differentially expressed genes (DEGs) were
      detected in lungs from both 201- and EV76-infected mice at 12h post-infection
      (hpi). DEGs in lungs of 201-infected mice exceeded 2000 at 48hpi, accompanied by
      sustained large numbers of DEGs in the liver and spleen; however, limited numbers
      of DEGs were detected in those organs of EV-infected mice. Remarkably, DEGs in
      lungs were significantly enriched in critical immune responses pathways in EV76
      infected but not 201-infected mice, including antigen processing and
      presentation, T cell receptor signaling among others. Pathological and bacterial
      load analyses confirmed the rapid systemic dissemination of 201-infection and the
      confined EV76-infection in lungs. Our results suggest that fully virulent Y.
      pestis inhibits both the innate and adaptive immune responses that are
      substantially stimulated in a self-limited infection, which update our holistic
      views on the transcriptomic response to pneumonic plague.

PMID- 27876298
TI  - Commentary to 'Gonadal dysgenesis in disorders of sex development (DSD):
      Diagnosis and surgical management'.

PMID- 27876299
TI  - [Single nucleotide polymorphisms in genes of endothelin-1 and receptor A
      associated to cardiovascular in essential hypertension].
AB  - INTRODUCTION: The endothelin system, for its vasoconstrictor action, is related
      to the development of essential hypertension (HTAe). The polymorphism analysis of
      their genes represents a new approach to the study of this disease. We propose to
      analyze the interaction between stages of essential hypertension (HTAe) and risk
      factors with polymorphisms 138ex1 ins/del A gene endothelin-1 (ET-1) and H323H
      receptor gene A ET-1 (ETRA). PATIENTS AND METHODS: We included 300 patients of
      both sexes, unrelated, who consecutively attended the clinic hypertension medical
      service. Each one underwent a complete physical examination, electrocardiogram,
      echocardiogram, and Rx thorax. The degree of severity of hypertension was
      determined in stages. The determination of polymorphisms was performed by
      amplification followed by cutting by specific restriction enzyme from DNA
      obtained from peripheral blood. RESULTS: The 46% of patients had HTAe controlled,
      17.6% had organ damage or cardiovascular, brain or kidney disease. It was
      observed that the 4A/4A carriers showed lower frequency of cardiovascular
      disease, kidney and brain (P<.032; 95% CI: 11.1-21.4). For H323H polymorphism,
      the evaluation by images showed a higher frequency of the dilations of left
      auricular (P=.02) and auricular fibrillation (P=.03) between the T/T carrier, a
      higher frequency of cardiomegaly was detected in C/C patients (P=.04).
      CONCLUSION: The genotypes, 4A/4A of the ET-1 gene and the T/T from ETRA gene
      might be involved in worse outcome of cardiovascular damage. Their identification
      could help recognize subgroups of the hypertensive patients with different risk.

PMID- 27876300
TI  - Functional Voice Disorders: The Importance of the Psychologist in Clinical Voice
      Assessment.
AB  - OBJECTIVES: The etiopathogenesis of functional voice disorders (FVDs) is
      multifactorial. The purpose of this study was to analyze the severity of
      depression and anxiety, and the incidence of affective and anxiety disorders, in
      patients who presented different types of FVDs and were followed at the
      University Clinic of Otolaryngology. DESIGN: This is a cross-sectional study.
      METHODS: After ENT observation, 83 women were classified into three groups:
      psychogenic voice disorder (PVD = 39), primary muscle tension voice disorder
      (MTVD1 = 16), and secondary muscle tension voice disorder (MTVD2 = 28). A
      psychologist assessed the severity of depression and anxiety using the Hamilton
      rating scales, and screened for affective and anxiety disorders using the Mini
      International Neuropsychiatric Interview. RESULTS: Significant differences in the
      mean values were found between the groups, with the MTVD1 group having higher
      levels of depression and anxiety. In affective disorders (current major
      depression and current mood disorder with psychotic symptoms) and in anxiety
      disorders (lifetime panic disorder, current generalized anxiety, and current
      panic disorder with agoraphobia), significant differences in association were
      found between groups. CONCLUSIONS: Groups presented with significant differences
      in depression and anxiety levels, and in some psychiatric diagnoses. Patients
      with FVDs should be independently assessed regarding their voice disorder
      classification. The integration of a psychologist in the clinical voice
      assessment team is essential, as findings have corroborated an important
      incidence of psychiatric disorders in FVDs patients.

PMID- 27876301
TI  - Overdrive and Edge as Refiners of "Belting"?: An Empirical Study Qualifying and
      Categorizing "Belting" Based on Audio Perception, Laryngostroboscopic Imaging,
      Acoustics, LTAS, and EGG.
AB  - OBJECTIVES: We aimed to study the categorizations "Overdrive" and "Edge" from the
      pedagogical method Complete Vocal Technique as refiners of the often ill-defined
      concept of "belting" by means of audio perception, laryngostroboscopic imaging,
      acoustics, long-term average spectrum (LTAS), and electroglottography (EGG).
      STUDY DESIGN: This is a case-control study. METHODS: Twenty singers were recorded
      singing sustained vowels in a "belting" quality refined by audio perception as
      "Overdrive" and "Edge." Two studies were performed: (1) a laryngostroboscopic
      examination using a videonasoendoscopic camera system (Olympus) and the
      Laryngostrobe program (Laryngograph); (2) a simultaneous recording of the EGG and
      acoustic signals using Speech Studio (Laryngograph). The images were analyzed
      based on consensus agreement. Statistical analysis of the acoustic, LTAS, and EGG
      parameters was undertaken using the Student paired t test. RESULTS: The two modes
      of singing determined by audio perception have visibly different laryngeal
      gestures: Edge has a more constricted setting than that of Overdrive, where the
      ventricular folds seem to cover more of the vocal folds, the aryepiglottic folds
      show a sharper edge in Edge, and the cuneiform cartilages are rolled in
      anteromedially. LTAS analysis shows a statistical difference, particularly after
      the ninth harmonic, with a coinciding first formant. The combined group showed
      statistical differences in shimmer, harmonics-to-noise ratio, normalized noise
      energy, and mean sound pressure level (P <= 0.05). CONCLUSION: "Belting" sounds
      can be categorized using audio perception into two modes of singing: "Overdrive"
      and "Edge." This study demonstrates consistent visibly different laryngeal
      gestures between these modes and with some correspondingly significant
      differences in LTAS, EGG, and acoustic measures.

PMID- 27876302
TI  - The risk of melanoma and hematologic cancers in patients with psoriasis.
AB  - BACKGROUND: The risk of melanoma and hematologic cancers in patients with
      psoriasis is controversial. OBJECTIVE: We sought to assess the risk of melanoma
      and hematologic cancers in patients with psoriasis, and the association with
      different treatments. METHODS: We used case-control and retrospective cohort
      designs to determine melanoma or hematologic cancer risk in patients with
      psoriasis. Risk with treatment type was assessed using Fisher exact test.
      RESULTS: Patients with psoriasis had 1.53 times greater risk of developing a
      malignancy compared with patients without psoriasis (P < .01). There were no
      significant differences in malignancy risk among patients treated with topicals,
      phototherapy, systemics, or biologic agents. Patients with psoriasis and
      malignancy did not have significantly worse survival than patients without
      psoriasis. LIMITATIONS: It is possible that patients developed malignancy
      subsequent to the follow-up time included in the study. CONCLUSION: Patients with
      psoriasis may experience an elevated risk of melanoma and hematologic cancers,
      compared with the general population. The risk is not increased by systemic or
      biologic psoriasis therapies.

PMID- 27876304
TI  - Effective use of 20% subcutaneous immunoglobulin therapy in a man with
      preexisting thrombi.

PMID- 27876303
TI  - Rapid visualization of nonmelanoma skin cancer.
AB  - BACKGROUND: Mohs micrographic surgery examines all margins of the resected sample
      and has a 99% cure rate. However, many nonmelanoma skin cancers (NMSCs) are not
      readily amenable to Mohs micrographic surgery. This defines an unmet clinical
      need to assess the completeness of non-Mohs micrographic surgery resections
      during surgery to prevent re-excision/recurrence. OBJECTIVE: We sought to examine
      the utility of quenched activity-based probe imaging to discriminate cancerous
      versus normal-appearing skin tissue. METHODS: The quenched activity-based probe
      GB119 was applied to NMSC excised from 68 patients. We validated activation of
      the probe for hematoxylin-eosin-confirmed cancerous tissue versus normal
      appearing skin tissue. RESULTS: Topical application of the probe differentiated
      basal cell carcinoma and squamous cell carcinoma from normal-appearing skin with
      overall estimated sensitivity and specificity of 0.989 (95% confidence interval
      0.940-1.00) and 0.894 (95% confidence interval 0.769-0.965), respectively. Probe
      activation accurately defined peripheral margins of NMSC as compared with
      conventional hematoxylin-eosin-based pathology. LIMITATIONS: This study only
      examined NMSC debulking excision specimens. The sensitivity and specificity for
      this approach using final NMSC excision margins will be clinically important.
      CONCLUSIONS: These findings merit further studies to determine whether quenched
      activity-based probe technology may enable cost-effective increased cure rates
      for patients with NMSC by reducing re-excision and recurrence rates with a rapid
      and easily interpretable technological advance.

PMID- 27876305
TI  - New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery
      for Gleason Score 8-10 Prostate Cancer.
AB  - BACKGROUND: The newly proposed five-tiered prostate cancer grading system (PCGS)
      divides Gleason score (GS) 8-10 disease into GS 8 and GS 9-10 on the basis of
      biochemical recurrence (BCR) following radical prostatectomy (RP) as an outcome.
      However, BCR does not necessarily portend worse survival outcomes. OBJECTIVE: To
      assess the significance of distinguishing GS 8 versus 9-10 disease in terms of
      long-term survival outcomes for both the preoperative setting using biopsy (Bx)
      GS and the postoperative setting with RP GS. DESIGN, SETTING, AND PARTICIPANTS:
      Of 23918 men who underwent RP between 1984 and 2014, there were 721 men with
      biopsy GS 8-10, and 1047 men with RP GS 8-10. OUTCOME MEASURES AND STATISTICAL
      ANALYSIS: Clinicopathologic characteristics were compared between men with GS 8
      and those with GS 9-10. We compared all-cause mortality (ACM) and prostate cancer
      specific mortality (PCSM) risk between the groups using Cox regression and
      competing-risks analyses, adjusting for other perioperative variables and death
      from other causes as the competing event. RESULTS AND LIMITATIONS: Compared to
      men with GS 8, men with GS 9-10 had later RP year and higher pathologic stage.
      Among men with Bx GS 8-10, 115 died (82 due to PC) with median follow-up of 3 yr
      (interquartile range [IQR] 1-7) for both overall and cancer-specific survival. Of
      men with RP GS 8-10, 221 died (151 due to PC) with median follow-up of 4 yr (IQR
      2-8) and 4 yr (IQR 2-9) for overall and cancer-specific survival, respectively.
      PC-specific survival rates were significantly lower for men with GS 9-10 compared
      to men with GS 8 for both Bx (hazard ratio [HR] 2.13, 95% confidence interval
      [CI] 1.37-3.30; p<0.01) and RP GS (HR 2.38, 95% CI 1.74-3.28; p<0.01). This
      association persisted in multivariable models after adjusting for perioperative
      variables. CONCLUSIONS: Men with GS 9-10 had higher ACM and PCSM rates compared
      to those with GS 8. GS 8 and GS 9-10 PC should be considered separately in both
      the preoperative and postoperative setting as suggested by the new PCGS. PATIENT
      SUMMARY: The prostate cancer grading system can predict mortality risk after
      radical prostatectomy (RP) for men with Gleason score 8-10 disease based on both
      biopsy and RP Gleason scores. There are significant differences in all-cause
      mortality and prostate cancer-specific mortality following surgery between men
      with Gleason score 8 and those with Gleason score 9-10 disease.

PMID- 27876307
TI  - First line treatment of Candida osteomyelitis of the sternum: Is there really a
      need for radical surgical debridement and reconstructive surgery in Candida
      osteomyelitis of the sternum after cardiac surgery?

PMID- 27876308
TI  - A cost-effective modification in progressive barbed suture closure of the
      abdominal donor site in DIEP and MS-TRAM patients: A review of surgical
      technique.

PMID- 27876306
TI  - Effects of HD-tDCS on memory and metamemory for general knowledge questions that
      vary by difficulty.
AB  - BACKGROUND: The ability to monitor one's own memory is an important feature of
      normal memory and is an aspect of 'metamemory'. Lesion studies have shown
      dissociations between memory and metamemory, but only single dissociations have
      been shown using transcranial direct current stimulation (tDCS). One potential
      reason that only single dissociations have been shown is that tDCS effects may be
      moderated by task difficulty. OBJECTIVE/HYPOTHESIS: We used high definition (HD)
      tDCS to test for dissociable roles of the dorsolateral prefrontal cortex (DLPFC)
      and anterior temporal lobe (ATL) in semantic long-term memory and metamemory
      tasks. We also tested whether general knowledge question difficulty moderated the
      effects of HD-tDCS. METHODS: Across 3 sessions, participants received active HD
      tDCS over the left DLPFC or left ATL, or sham HD-tDCS during general knowledge
      recall and recognition tests, and a 'feeling-of-knowing' metamemory task. General
      knowledge questions were blocked by difficulty. Repeated measures ANOVAs were
      used to examine the effects of HD-tDCS on memory and metamemory tasks by memory
      question difficulty. RESULTS: HD-tDCS over the ATL led to improved recall
      compared to DLPFC and sham HD-tDCS, and this occurred only for medium difficulty
      questions. In contrast, for non-recalled questions, HD-tDCS over the DLPFC led to
      improved recognition accuracy and improved feeling-of-knowing accuracy compared
      to ATL and sham HD-tDCS, and this was not moderated by memory question
      difficulty. CONCLUSION (S): HD-tDCS can be used to dissociate the roles of the
      ATL and DLPFC in different memory and 'metamemory' tasks. The effects of HD-tDCS
      on task may be moderated by task difficulty, depending on the nature of the task
      and site of stimulation.

PMID- 27876309
TI  - Vertical breast measurement in East Asian women: A guide for mastopexy and
      reduction to form nonptotic breasts in unilateral prosthetic breast
      reconstruction.
AB  - BACKGROUND: Following unilateral breast cancer surgery, mastopexy and reduction
      of the unaffected breast are often performed to obtain symmetrical breasts. The
      use of implants in breast reconstruction results in a nonptotic breast. To
      achieve symmetry following the procedure, the unaffected side should be nonptotic
      too. However, no study has yet reported any indices for the design of mastopexy
      and reduction in this direction. We present a new method of preoperative design
      that uses vertical breast measurements to form nonptotic breasts according to
      individual breast shapes. METHODS: We performed vertical breast measurements of
      the unaffected breasts of 193 patients scheduled to undergo surgery for
      unilateral breast cancer. The vertical base dimension (VBD) and vertical surface
      dimension (VSD) of the ptotic and nonptotic breasts and the height of the nipple
      in the nonptotic breast were measured in centimeters. RESULTS: The borderline
      between ptotic and nonptotic breasts was expressed using the formula VSD = 1.13 *
      VBD + 1.86. The height of the nipple in nonptotic breasts was 0.8 times the
      distance between the sternal notch and lowest point of the inframammary fold on
      the midline. From these findings, we formulated a new method for forming a
      nonptotic breast from a ptotic breast using an inverted T design. CONCLUSION:
      These results can be used for the design of mastopexy and reduction when forming
      a nonptotic breast on the unaffected side. These procedures can be performed
      without significantly lifting the nipple-areolar complex if required during
      unilateral prosthetic breast reconstruction.

PMID- 27876312
TI  - Erratum to "Direct oral anticoagulant use and stent thrombosis following an acute
      coronary syndrome: A potential new pharmacological option?" [Arch. Cardiol. Dis.
      109 (5) (2016) 359-369].

PMID- 27876310
TI  - Impact of Atrial Natriuretic Peptide Value for Predicting Paroxysmal Atrial
      Fibrillation in Ischemic Stroke Patients.
AB  - INTRODUCTION: The impact of atrial natriuretic peptide (ANP) value for predicting
      paroxysmal atrial fibrillation (pAF) in ischemic stroke patients remains
      uncertain. METHODS: The consecutive 222 ischemic stroke patients (median 77 [IQR
      68-83] years old, 93 females) within 48 hours after onset were retrospectively
      studied. Plasma ANP and brain natriuretic peptide (BNP) levels were
      simultaneously measured at admission. Of all, 158 patients had no evidence of
      atrial fibrillation (AF) (sinus rhythm [SR] group), 25 patients had pAF (pAF
      group), and the other 39 patients had chronic AF (cAF group). We investigated
      predicting factors for pAF, with focus on ANP, BNP, and ANP/BNP ratio. RESULTS:
      ANP value was significantly higher in the pAF than in the SR group (97 [50-157]
      mg/dL versus 42 [26-72] mg/dL, P < .05) and further increased in the cAF group
      (228 [120-392], P < .05 versus pAF and SR groups). Similarly, the BNP value was
      higher in the pAF than in the SR group (116 [70-238] mg/dL versus 34 [14-72]
      mg/dL, P < .05) and further increased in the cAF group (269 [199-423], P < .05
      versus pAF and SR groups). ANP/BNP ratio was lower in the pAF and cAF groups than
      in the SR group (.6 [.5-1.2] and .7 [.5-1.0] versus 1.3 [.8-2.4], both P < .05].
      Multivariate analysis in the SR and pAF groups (n = 183) demonstrated that age,
      congestive heart failure, ANP, and BNP, but not ANP/BNP ratio, were independent
      predictors for detecting pAF. Receiver operating characteristic curve analysis
      further showed that area under the curve was similar between ANP and BNP (.76 and
      .80). CONCLUSIONS: ANPmay be clinically useful for detecting pAF in ischemic
      stroke patients as well as BNP.

PMID- 27876311
TI  - Circulating Biomarkers in Cerebral Autosomal Dominant Arteriopathy with
      Subcortical Infarcts and Leukoencephalopathy Patients.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy
      presenting with variable features, including migraine, psychiatric disorders,
      stroke, and cognitive decline and variable disability. On neuroimaging, CADASIL
      is characterized by leukoencephalopathy, multiple lacunar infarcts, and
      microbleeds. Previous studies suggest a possible role of endothelial impairment
      in the pathogenesis of the disease. METHODS: We assessed plasma levels of von
      Willebrand factor (vWF) and thrombomodulin (TM) and the blood levels of
      endothelial progenitor cells (EPCs) and circulating progenitor cells (CPCs) in 49
      CADASIL patients and 49 age-matched controls and their association with
      clinical/functional and neuroimaging features. RESULTS: In multivariate analysis,
      CADASIL patients had significantly higher vWF and lower EPC levels. TM levels
      were similar in the 2 groups. CADASIL patients with a more severe clinical
      phenotype (history of stroke or dementia) presented lower CPC levels in
      comparison with patients with a milder phenotype. On correlation analysis, lower
      CPC levels were associated with worse performances on neuropsychological, motor
      and functional tests, and with higher lesion load on brain magnetic resonance
      imaging (degree of leukoencephalopathy and number of lacunar infarcts).
      CONCLUSIONS: This is the first CADASIL series in which multiple circulating
      biomarkers have been studied. Our findings support previous studies on the
      presence and the possible modulating effect of endothelial impairment in the
      disease. Furthermore, our research data suggest that blood CPCs may be markers of
      disease severity.

PMID- 27876313
TI  - Lysosomal acid lipase deficiency: Expanding differential diagnosis.
AB  - The differential diagnoses for metabolic liver diseases may be challenging in
      clinical settings, which represents a critical issue for disorders such as
      lysosomal acid lipase deficiency (LAL-D). LAL-D is caused by deficient activity
      of the LAL enzyme, resulting in the accumulation of cholesteryl esters and
      triglycerides throughout the body, predominately in the liver, spleen,
      gastrointestinal tract, and blood vessel walls. LAL-D is a progressive, multi
      organ disease with early mortality and significant morbidity characterized by a
      combination of hepatic dysfunction and dyslipidemia. Evidence suggests LAL-D may
      be substantially underdiagnosed or misdiagnosed, which is critical given that
      disease progression can be unpredictable, with liver failure and/or accelerated
      atherosclerosis potentially contributing to early mortality. However, given the
      development of a simple diagnostic test and recently approved treatment, LAL-D
      should be incorporated into the differential diagnosis in relevant clinical
      settings. LAL-D can be diagnosed using an LAL enzyme-based biochemical test,
      thereby allowing for active monitoring of patients to detect potential disease
      complications and consider treatment options including diet, lipid-lowering
      medication, and treatment with sebelipase alfa, a recombinant enzyme replacement
      therapy shown to provide clinical benefit and improve disease-relevant markers in
      clinical trials. To illustrate the complexity of diagnosing LAL-D, this
      manuscript will describe the path to diagnosing LAL-D in a series of patient
      cases in which LAL-D was diagnosed as well as in patients where other diseases,
      such as Gaucher disease and Niemann-Pick disease, were initially suspected.

PMID- 27876314
TI  - Risk of Jaw Osteonecrosis After Intravenous Bisphosphonates in Cancer Patients
      and Patients Without Cancer.
AB  - OBJECTIVE: To compare the risk of jaw osteonecrosis after intravenous (IV)
      bisphosphonate administered to patients with cancer vs patients without cancer.
      PATIENTS AND METHODS: We conducted a retrospective cohort study of a 5% national
      sample of Medicare patients administered IV bisphosphonate from January 1, 2008,
      through December 31, 2013, for cancer vs noncancer indications. Probable jaw
      osteonecrosis was estimated with an algorithm including diagnoses, surgical
      procedures, and imaging studies. A non-IV bisphosphonate comparison group
      included patients prescribed an oral bisphosphonate for 30 days or less. RESULTS:
      During follow-up, 40 (0.42%) out of 9482 patients with cancer developed probable
      jaw osteonecrosis compared with 8 (0.05%) out of 16,046 patients without cancer.
      In a Cox multivariable survival analysis controlling for patient characteristics
      and number of IV zoledronic infusions, patients without cancer had a hazard ratio
      of 0.17 (95% CI, 0.06-0.46) for developing jaw osteonecrosis compared with those
      with cancer. The lower rate of jaw osteonecrosis in patients without cancer was
      also confirmed in a number of sensitivity analyses. CONCLUSION: The low rate of
      jaw osteonecrosis in patients with osteoporosis who receive IV bisphosphonate
      should be weighed against the benefit of those agents in preventing hip and other
      fractures.

PMID- 27876316
TI  - Optimism During Hospitalization for First Acute Myocardial Infarction and Long
      Term Mortality Risk: A Prospective Cohort Study.
AB  - OBJECTIVE: To assess the association between dispositional optimism, defined as
      generalized positive expectations about the future, and long-term mortality in
      young survivors of myocardial infarction (MI). PATIENTS AND METHODS: A subcohort
      of 664 patients 65 years and younger, drawn from the longitudinal Israel Study of
      First Acute Myocardial Infarction, completed an adapted Life Orientation Test
      (LOT) questionnaire during their index hospitalization between February 15, 1992,
      and February 15, 1993. Additional sociodemographic, clinical, and psychosocial
      variables were assessed at baseline; mortality follow-up lasted through December
      31, 2015. Cox proportional hazards regression models were fit to assess the
      hazard ratios for mortality associated with LOT-derived optimism. RESULTS: The
      mean age of the participants was 52.4+/-8.6 years; 98 (15%) were women. The
      median follow-up period was 22.4 years (25th-75th percentiles, 16.1-22.8 years),
      during which 284 patients (43%) had died. The mean LOT score was 16.5+/-4.1.
      Incidence density rates for mortality in increasing optimism tertiles were 25.4,
      25.8, and 16.0 per 1000 person-years, respectively (P<.01). With sequential
      adjustment for sociodemographic, clinical, and psychosocial variables, a
      decreased mortality was associated with the upper tertile (adjusted hazard ratio,
      0.67; 95% CI, 0.47-0.95). A nonlinear inverse relationship was observed using
      spline analysis, with the slope increasing sharply beyond the median LOT score.
      CONCLUSION: Higher levels of optimism during hospitalization for MI were
      associated with reduced mortality over a 2-decade follow-up period. Optimism
      training and positive psychology should be examined as part of psychosocial
      interventions and rehabilitation after MI.

PMID- 27876317
TI  - Discovery of SOAT2 inhibitors from synthetic small molecules.
AB  - Synthesis of new functionalized molecules and identification of biofunctional
      molecules can lead to the development of therapeutic leads and molecular tools
      for biomedical research. We have recently reported oxa-hetero-Diels-Alder
      reactions of enones with isatins to provide functionalized spirooxindole
      tetrahydropyran derivatives. Twenty-one compounds from the spirooxindole
      tetrahydropyran derivatives and related molecules were screened for inhibition of
      sterol O-acyltransferase (SOAT) isozymes SOAT1 and SOAT2. Three racemic
      derivatives inhibited the SOAT2 isozyme with three-fold or better selectivity for
      SOAT2 than for SOAT1. The enantiomerically enriched forms of the most efficient
      racemic inhibitor of SOAT2 were further evaluated; one enantiomer inhibited SOAT2
      with an IC50 of 1.5MUM and was 10-fold more selective for SOAT2 than SOAT1.

PMID- 27876315
TI  - Cardiorespiratory Fitness and Incidence of Major Adverse Cardiovascular Events in
      US Veterans: A Cohort Study.
AB  - OBJECTIVE: To assess the association between exercise capacity and the risk of
      major adverse cardiovascular events (MACEs). PATIENTS AND METHODS: A symptom
      limited exercise tolerance test was performed to assess exercise capacity in
      20,590 US veterans (12,975 blacks and 7615 whites; mean +/- SD age, 58.2+/-11.0
      years) from the Veterans Affairs medical centers in Washington, District of
      Columbia, and Palo Alto, California. None had a history of MACE or evidence of
      ischemia at the time of or before their exercise tolerance test. We established
      quintiles of cardiorespiratory fitness (CRF) categories based on age-specific
      peak metabolic equivalents (METs) achieved. We also defined the age-specific MET
      level associated with no risk for MACE (hazard ratio [HR], 1.0) and formed 4
      additional CRF categories based on METs achieved below (least fit and low fit)
      and above (moderately fit and highly fit) that level. Multivariate Cox models
      were used to estimate HR and 95% CIs for mortality across fitness categories.
      RESULTS: During follow-up (median, 11.3 years; range, 0.3-33.0 years), 2846
      individuals experienced MACEs. The CRF-MACE association was inverse and graded.
      The risk for MACE declined precipitously for those with a CRF level of 6.0 METs
      or higher. When considering CFR categories based on the age-specific MET
      threshold, the risk increased for those in the 2 CFR categories below that
      threshold (HR, 1.95; 95% CI, 1.73-2.21 and HR, 1.41; 95% CI, 1.27-1.56 for the
      least-fit and low-fit individuals, respectively) and decreased for those above it
      (HR, 0.77; 95% CI, 0.68-0.87 and HR, 0.57; 95% CI, 0.48-0.67 for moderately fit
      and highly fit, respectively). CONCLUSION: Increased CRF is inversely and
      independently associated with the risk for MACE. When an age-specific MET
      threshold was defined, the risk for MACE increased significantly for those below
      that threshold and decreased for those above it (P<.001).

PMID- 27876318
TI  - Selectivity switch between FAK and Pyk2: Macrocyclization of FAK inhibitors
      improves Pyk2 potency.
AB  - Herein, we describe the synthesis of Pyk2 inhibitors via macrocyclization of FAK
      and dual Pyk2-FAK inhibitors. We identified macrocycle 25a as a highly potent
      Pyk2 inhibitor (IC50=0.7nM), with ~175-fold improvement in Pyk2 potency as
      compared to its acyclic counterpart. In many cases, macrocyclization improved
      Pyk2 potency while weakening FAK potency, thereby improving the Pyk2/FAK
      selectivity ratio for this structural class of inhibitors. Various macrocyclic
      linkers were studied in an attempt to optimize Pyk2 selectivity. We observed
      macrocyclic atropisomerism during the synthesis of 19-membered macrocycles 10a-d,
      and successfully obtained crystallographic evidence of one atropisomer (10a
      AtropB) preferentially bound to Pyk2.

PMID- 27876319
TI  - Development of a triazole class of highly potent Porcn inhibitors.
AB  - The acyltransferase Porcupine (Porcn) is essential for the secretion of Wnt
      proteins which contribute to embryonic development, tissue regeneration, and
      tumorigenesis. We have previously discovered four molecular scaffolds harboring
      Porcn-inhibitory activity. Comparison of their structures led to the
      identification of a general scaffold that can be readily assembled by modular
      synthesis. We report herein the development of a triazole version of this new
      class of Porcn inhibitors. This study yielded IWP-O1, a Porcn inhibitor with an
      EC50 value of 80pM in a cultured cell reporter assay of Wnt signaling.
      Additionally, IWP-O1 has significantly improved metabolic stability over our
      previously reported Porcn inhibitors.

PMID- 27876322
TI  - Teen Cuisine: Impacting Dietary Habits and Food Preparation Skills in
      Adolescents.

PMID- 27876321
TI  - An Exploration of How Mexican American WIC Mothers Obtain Information About
      Behaviors Associated With Childhood Obesity Risk.
AB  - OBJECTIVE: To explore how a sample of Mexican American mothers with preschool
      aged children recruited from a Midwestern Special Supplemental Nutrition Program
      for Women, Infants, and Children (WIC) clinic obtained information about 4
      behaviors associated with childhood obesity risk: eating, physical activity,
      screen time, and sleep. DESIGN: One-on-one structured interviews in which
      participants were asked how they communicated with family, learned to take care
      of their first infant, and obtained information about the 4 targeted behaviors
      for their preschool-aged child. SETTING: An urban WIC clinic in the Midwest.
      PARTICIPANTS: Forty Mexican-descent mothers enrolled in WIC with children aged 3
      4 years. PHENOMENON OF INTEREST: Exposure to information about the 4 targeted
      behaviors among Mexican-descent mothers participating in WIC. ANALYSIS:
      Quantitative and qualitative data were used to characterize and compare across
      participants. RESULTS: Participants primarily obtained information from their
      child's maternal grandmother during their first child's infancy and from health
      professionals for their preschool-aged child. Participants typically obtained
      information through interpersonal communication, television, and magazines.
      Participants were most interested in healthy eating information and least
      interested in screen time information. Some participants did not seek
      information. CONCLUSIONS AND IMPLICATIONS: Participants engaged in different
      patterns of information seeking across their child's development and the 4
      behaviors, which suggests that future research should be behaviorally specific.
      Findings from this study suggest several hypotheses to test in future research.

PMID- 27876323
TI  - Collection Methods for the 24-Hour Dietary Recall as Used in the Expanded Food
      and Nutrition Education Program.
AB  - OBJECTIVE: Identify practices for the collection of the 24-hour dietary recall
      (24HR) as used by the Expanded Food and Nutrition Education Program (EFNEP) to
      assess the fidelity with which dietary data are collected. METHODS: An electronic
      survey sent nationally to all 75 EFNEP coordinators to assess methodology for
      collection, staff training, and coding of 24HR. RESULTS: A total of 67 surveys
      were returned, 53 of which were usable: 57% of programs used multiple collection
      periods (previous day vs previous 24 hours), 36% did not use a consistent number
      of passes in recall collection; only 17% exclusively used the validated 5-pass
      method; 88% trained paraprofessionals for <=8 hours on recall collection and >6
      different training programs were used; and 86% of programs used multiple coders.
      CONCLUSIONS AND IMPLICATIONS: The wide variation in reported collection,
      training, and coding practices raises concerns about the validity of the recall
      data and the appropriateness of combining data from multiple programs. To improve
      consistency, EFNEP could establish standardized methods for training, data
      collection, and data entry for the 24HR. These results may encourage the national
      program office to establish programmatic change that will support the fidelity of
      collection methods across all programs.

PMID- 27876320
TI  - Marine sponge alkaloids as a source of anti-bacterial adjuvants.
AB  - Novel approaches that do not rely upon developing microbicidal compounds are
      sorely needed to combat multidrug resistant (MDR) bacteria. The potential of
      marine secondary metabolites to serve as a source of non-traditional anti
      bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids
      inhibit biofilm formation and suppress antibiotic resistance.

PMID- 27876324
TI  - Developing a Questionnaire to Evaluate College Students' Knowledge, Attitude,
      Behavior, Self-efficacy, and Environmental Factors Related to Canned Foods.
AB  - OBJECTIVE: Develop a questionnaire to measure students' knowledge, attitude,
      behavior, self-efficacy, and environmental factors related to the use of canned
      foods. METHODS: The Knowledge-Attitude-Behavior Model, Social Cognitive Theory,
      and Canned Foods Alliance survey were used as frameworks for questionnaire
      development. Cognitive interviews were conducted with college students (n = 8).
      Nutrition and survey experts assessed content validity. Reliability was measured
      via Cronbach alpha and 2 rounds (1, n = 81; 2, n = 65) of test-retest statistics.
      Means and frequencies were used. RESULTS: The 65-item questionnaire had a test
      retest reliability of .69. Cronbach alpha scores were .87 for knowledge (9
      items), .86 for attitude (30 items), .80 for self-efficacy (12 items), .68 for
      canned foods use (8 items), and .30 for environment (6 items). CONCLUSIONS AND
      IMPLICATIONS: A reliable questionnaire was developed to measure perceptions and
      use of canned foods. Nutrition educators may find this questionnaire useful to
      evaluate pretest-posttest changes from canned foods-based interventions among
      college students.

PMID- 27876325
TI  - Does Early Goal-Directed Therapy Decrease Mortality Compared with Standard Care
      in Patients with Septic Shock?
AB  - BACKGROUND: Current international guidelines for the treatment of patients with
      severe sepsis and septic shock recommend that patients receive targeted care to
      various physiologic endpoints, thereby optimizing tissue perfusion and
      oxygenation. These recommendations are primarily derived from a protocol
      published >15 years ago, which was viewed by many as complex and was therefore
      not widely adopted. Instead, many emergency physicians focused on the
      administration of early antibiotics, source control, aggressive fluid
      resuscitation, vasoactive medications as needed to maintain mean arterial blood
      pressure, and careful monitoring of these patients. The primary goal of this
      literature search was to determine if there is a mortality benefit to the early
      goal-directed protocol recommended by current international sepsis guidelines
      compared to current usual care. METHODS: A MEDLINE literature search was
      performed for studies published between January 1, 2010 and December 31, 2015.
      Studies were limited to the English language, human randomized controlled trials,
      meta-analyses, prospective trials, and retrospective cohort trials that met
      specific keyword search criteria. Case reports, case series, and review articles
      were excluded. All selected articles then underwent a structured review by the
      authors. RESULTS: Seven thousand four hundred twenty studies were initially
      screened; after the final application of inclusion and exclusion criteria, 10
      studies were formally analyzed. Each study then underwent a rigorous review and
      evaluation from which a formal recommendation was made. CONCLUSION: There is no
      difference in mortality between current usual care and the goal-directed approach
      recommended by current international guidelines for patients with severe sepsis
      and septic shock.

PMID- 27876326
TI  - Hypertriglyceridemia-induced Acute Pancreatitis.

PMID- 27876327
TI  - Endotracheal Intubation with the King Laryngeal TubeTM In Situ Using Video
      Laryngoscopy and a Bougie: A Retrospective Case Series and Cadaveric Crossover
      Study.
AB  - BACKGROUND: Removal of a functioning King laryngeal tube (LT) prior to
      establishing a definitive airway increases the risk of a "can't intubate, can't
      oxygenate" scenario. We previously described a technique utilizing video
      laryngoscopy (VL) and a bougie to intubate around a well-seated King LT with the
      balloons deflated; if necessary, the balloons can be rapidly re-inflated and
      ventilation resumed. OBJECTIVE: Our objective is to provide preliminary
      validation of this technique. METHODS: Emergency physicians performed all
      orotracheal intubations in this two-part study. Part 1 consisted of a historical
      analysis of VL recordings from emergency department (ED) patients intubated with
      the King LT in place over a two-year period at our institution. In Part 2, we
      analyzed VL recordings from paired attempts at intubating a cadaver, first with a
      King LT in place and then with the device removed, with each physician serving as
      his or her own control. The primary outcome for all analyses was first-pass
      success. RESULTS: There were 11 VL recordings of ED patients intubated with the
      King LT in place (Part 1) and 11 pairs of cadaveric VL recordings (Part 2). The
      first-pass success rate was 100% in both parts. In Part 1, the median time to
      intubation was 43 s (interquartile range [IQR] 36-60 s). In Part 2, the median
      time to intubation was 23 s (IQR 18-35 s) with the King LT in place and 17 s (IQR
      14-18 s) with the King LT removed. CONCLUSIONS: Emergency physicians successfully
      intubated on the first attempt with the King LT in situ. The technique described
      in this proof-of-concept study seems promising and merits further validation.

PMID- 27876328
TI  - Best Clinical Practice: Controversies in Transient Ischemic Attack Evaluation and
      Disposition in the Emergency Department.
AB  - BACKGROUND: Transient ischemic attack (TIA) affects over 200,000 patients
      annually in the United States, and it precedes approximately 14% to 23% of
      strokes. Patients are typically admitted for evaluation and management.
      OBJECTIVE: This review investigates the controversies of emergency department
      (ED) evaluation of TIA, including imaging, clinical risk scores, rapid diagnostic
      protocols, and disposition. DISCUSSION: TIA is a common condition, with over
      200,000 patients affected annually, and is associated with risk of stroke. TIA is
      defined as a brief episode of neurologic dysfunction with no permanent
      infarction. A great deal of literature has evaluated the use of imaging, clinical
      risk scores, and diagnostic protocols in the evaluation of TIA. Head computed
      tomography noncontrast is not reliable to diagnose acute infarction. Magnetic
      resonance imaging with diffusion-weighted imaging displays greater diagnostic
      ability. Carotid imaging includes magnetic resonance angiography, computed
      tomography angiography, and Doppler with ultrasound. Risk scores that predict
      future stroke are not reliable when utilized alone. With imaging, including
      magnetic resonance imaging, patients with low-risk scores can be discharged. The
      use of ED diagnostic protocols and observation units can reduce length of stay
      while improving patient treatment and reducing stroke rate. An algorithm is
      provided for evaluation and disposition in the ED. CONCLUSIONS: TIA is a
      condition with high risk for stroke. Imaging is often not reliable, nor is the
      use of risk scores alone. The American College of Emergency Physicians provides a
      Level B Recommendation for the use of rapid diagnostic protocols to determine
      patient short-term risk for stroke while avoiding the reliance on stratification
      instruments to discharge patients from the ED.

PMID- 27876329
TI  - Four-Factor Versus Three-Factor Prothrombin Complex Concentrate: Is More Always
      Better?

PMID- 27876330
TI  - Pneumomediastinum, Pneumothorax, and Subcutaneous Emphysema Caused by
      Colonoscopic Perforation: A Report of Two Cases.
AB  - BACKGROUND: Although colonoscopy is generally a safe procedure, lethal
      complications can occur. Colonoscopic perforation is one of the most serious
      complications, and it can present with various clinical symptoms and signs.
      Aggravating abdominal pain and free air on simple radiography are representative
      clinical manifestations of colonoscopic perforation. However, unusual symptoms
      and signs, such as dyspnea and subcutaneous emphysema, which are less likely to
      be related with complicating colonoscopy, may obscure correct clinical diagnosis.
      We present two cases of pneumomediastinum, pneumothorax, and subcutaneous
      emphysema caused by colonoscopic perforation. CASE REPORT: A 75-year-old woman
      and a 65-year-old man presented with dyspnea, and facial swelling and abdominal
      pain, respectively. In the first case, symptoms occurred during polypectomy,
      whereas they occurred after polypectomy in the second case. Chest radiograph and
      computed tomography scans revealed pneumomediastinum, pneumothorax, and
      subcutaneous emphysema in the neck. During both operations, an ascending colonic
      subserosa filled with air bubbles was observed, and laparoscopic right
      hemicolectomy was performed in the first case. In the second case, after
      mobilization of the right colon, retroperitoneal colonic perforation was
      identified and primary repair was performed. The postoperative course was
      uneventful. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: These cases show
      the unusual clinical manifestations of colonoscopic perforation, which depend on
      the mechanism of perforation. Awareness of these less typical manifestations is
      crucial for prompt diagnosis and management for an emergency physician.

PMID- 27876331
TI  - Inferior Phrenic Artery-Related Hemoptysis.

PMID- 27876332
TI  - Long-term results after sleeve gastrectomy: A systematic review.
AB  - Sleeve gastrectomy (SG) has become one of the most commonly used bariatric
      procedures worldwide. However, data regarding long-term results remain
      insufficient. The aim of this study was to review the long-term results after SG.
      We conducted a comprehensive literature search of Medline and the Cochrane
      Library for articles published until May 2016 on the long-term results (>5 yr)
      after SG. Studies representing outcomes of SG were included if they reported>=5
      year results that contained at least one outcome of interest-weight loss, co
      morbidities, long-term complications, or quality of life-and SG was performed as
      a primary procedure. Of the 297 initially identified articles, 277 studies met
      the exclusion criteria, and 20 met the inclusion criteria. SG was performed on
      2713 patients and 1626 patients reached the>=5-year follow-up point. Among the
      patients, 71.3% were women and 28.7% were men. The mean preoperative body mass
      index was 46.9 kg/m2. The duration of follow-up ranged 5 to 11 years. The mean 5
      year follow-up rate was 66% (range, 57%-100%). The mean percentage excess weight
      loss was 58.4%, 59.5%, 56.6%, 56.4%, and 62.5% at 5, 6, 7, 8, and 11 years,
      respectively. Five years after SG, the resolution or improvement of type 2
      diabetes was observed in 77.8% of patients, and arterial hypertension,
      dyslipidemia, obstructive sleep apnea, gastroesophageal reflux disease, and
      degenerative joint diseases had improved or resolved in 68.0%, 65.9%, 75.8%,
      30.6%, and 55.7% of patients, respectively. This systematic review suggests that
      SG can lead to substantial and lasting excess weight loss and significant
      improvement in obesity-related co-morbidities. However, the lack of randomized
      clinical trials, low follow-up rates, and poorly reported data regarding co
      morbidities and quality of life in many of the studies indicate that these
      findings should be interpreted with caution.

PMID- 27876333
TI  - Unexpected Ectopic Pancreatic tissue during laparoscopic bariatric surgery. Case
      report and literature review.

PMID- 27876334
TI  - Overall and cause-specific mortality after Roux-en-Y gastric bypass surgery: A
      nationwide cohort study.
AB  - BACKGROUND: Few population-based studies provide data on mortality after
      bariatric surgery. We hypothesized that hypoglycemia could be an underdiagnosed
      cause of death. OBJECTIVES: To examine perioperative, all-cause, and cause
      specific long-term mortality in Roux-en-Y gastric bypass (RYGB) patients versus
      population comparisons. SETTING: Danish nationwide population-based cohort study.
      METHODS: We included all 9895 patients who underwent RYGB during 2006-2010, and a
      1:25 age- and gender-matched comparison cohort (n = 247,366) (0.3% lost to follow
      up). We compared mortality rates and computed mortality rate ratios (MRR) for all
      cause and cause-specific mortality using Cox regression analysis. For deceased
      RYGB patients (n = 91), we conducted a detailed medical record audit. RESULTS:
      The perioperative (30-days) mortality after RYGB was .04% (4/9895). After 4.2
      years, RYGB-related mortality (deaths due to intestinal obstruction/intra
      abdominal leakage) was .15% (16/9895). All-cause mortality was very similar in
      the 2 cohorts (median age, 40.2 years; 21.7% men): RYGB cohort, .89% (n = 91);
      comparison cohort, .92% (n = 2204); MRR = 1.03 (95% confidence interval [CI], .84
      1.27). Mortality due to suicide (2.78; 95% CI, 1.44-5.33), accidents (2.29; 95%
      CI, 1.16-4.54), gastrointestinal diseases (2.01; 95% CI, 1.06-3.84), and
      infectious diseases (1.75; 95% CI, .98-3.17) was higher in the RYGB cohort versus
      comparison groups, but mortality from cancer was lower (0.43; 95% CI, .27-.70).
      Our medical record audit indicated that 8% of deaths after RYGB (n = 7) were
      possibly hypoglycemia related. CONCLUSION: Perioperative mortality after RYGB is
      low in Denmark, and subsequent all-cause mortality is similar to that of matched
      comparisons. After RYGB, patients have substantially increased mortality due to
      external causes such as suicide, accidents, and possibly hypoglycemia.

PMID- 27876335
TI  - Globularia alypum methanolic extract improves burn wound healing process and
      inflammation in rats and possesses antibacterial and antioxidant activities.
AB  - Burns are known as one of the most common and destructive forms of injury with a
      vast spectrum of consequences. Despite the discovery of various antibacterial and
      antiseptic agents, burn wound healing still has remained a challenge to modern
      medicine. Plants have been considered as potential agents for prevention and
      treatment of disorders in recent years. Globularia alypum L. (GA) is widely used
      in folk medicine against skin diseases and abscesses, however there is no
      scientific evidence justifying its use. This study aimed to evaluate the wound
      healing and anti-inflammatory effect, the antibacterial and antioxidant
      activities, as well as the chemical compositions of GA methanolic extract (GAME).
      Chemical compounds of GAME were examined by GC-MS. Wound healing effect was
      assessed by second-degree burn wounds in rats, anti-inflammatory activity was
      studied by carrageenan-induced rat paw edema, antioxidant activity was estimated
      by the DPPH, reducing power and beta-carotene tests and antimicrobial activity
      was tested against 6 bacteria. A total of 17 compounds were identified. GAME
      treated rats showed an improvement in healing process and carrageenan-induced
      hind paws edema as assessed by histological and biochemical investigations,
      compared to the control. A significant antioxidant and antibacterial activities
      were also observed in GAME-treated rats. GAME revealed a burn wound healing
      activity probably due to the anti-inflammatory, antimicrobial and antioxidant
      activities of its phytochemical contents. Thus, this study confirms its
      traditional use, however further more precise studies are needed for future
      clinical application.

PMID- 27876336
TI  - Inhibition of protein glycation, antioxidant and antiproliferative activities of
      Carpobrotus edulis extracts.
AB  - Carpobrotus edulis is an important South African medicinal plants used as a food
      and therapeutic agent in traditional medicine. The aim of this study was to
      determine the phytochemical content, antioxidant, antiglycation and cytotoxic
      effect against Human Colon Cancer Cell Line (HCT-116) of aqueous and ethanol
      water (1:1v/v) extracts of Carpobrotus edulis.The content of total phenolics and
      flavonoids in aqueous and ethanol-water extract were 151.99MUg and 66.35MUg
      gallic acid equivalents/mg of dry extract, and 38.84MUg and 21.96MUg quercetin/mg
      of dry extract, respectively. Furthermore, phenolic compositions analysis
      indicated the presence of seven majority compounds including sinapic acid,
      ferulic acid, luteolin7-o-glucoside, hyperoside, isoquercitrin, ellagic acid and
      isorhamnetin 3-O-rutinoside. The ethanol-water extract (100-1000MUg/mL) showed
      better antioxidant activity than aqueous extract. Furthermore, Carpobrotus edulis
      extracts, especially ethanol-water extract significantly inhibited the formation
      of fluorescent advanced glycation end products, prevented oxidation-induced
      protein damage and exhibited a cytotoxic effect against HCT116 cells, with a
      significant decrease in cell viability after 24h of incubation. The results
      obtained suggest that the Carpobrotus edulis extracts could be used as an easily
      accessible source of natural antioxidants and as potential phytochemicals against
      protein glycation and colon cancer.

PMID- 27876337
TI  - Beneficial effect of carvone, a dietary monoterpene ameliorates hyperglycemia by
      regulating the key enzymes activities of carbohydrate metabolism in
      streptozotocin-induced diabetic rats.
AB  - Diabetes mellitus is a common metabolic/endocrine disorder characterized by
      inadequate control of carbohydrate metabolism and causes serious health issues.
      This study evaluates the effect of carvone, a novel monoterpene ketone, on
      carbohydrate metabolic enzymes in the liver of normal and streptozotocin (STZ)
      induced diabetic rats. Diabetes was induced by a single intraperitoneal injection
      of STZ (40mg/kg b.w). STZ intoxication led to a significant increase in the
      levels of plasma glucose, glycosylated hemoglobin (HbA1c) and decrease in the
      levels of insulin and hemoglobin (Hb). The activities of carbohydrate metabolic
      enzymes, glycogen, enzymatic antioxidants in pancreas and hepatic markers content
      were also altered. The daily oral administration of carvone (50mg/kg b.w) to
      diabetic rats for 30days resulted a significant decline in the levels of plasma
      glucose, HbA1c and significant improve in the levels of Hb and insulin. The
      reversed activities of carbohydrate metabolic enzymes, enzymic antioxidants and
      hepatic marker enzymes in diabetic rats were renovated to near normal level by
      the administration of carvone. The obtained results were compared with
      glyclazide, a standard oral hypoglycemia drug. Histopathological analysis of
      liver and pancreas and immunohistochemistry of pancreas revealed that treatment
      with carvone reduced the STZ-induced damage to hepatic and beta-cells of the
      pancreas. From our results, carvone regulates carbohydrate metabolism by
      ameliorating the key enzymes in the hepatic tissues of STZ-induced diabetic rats
      however further studies and safety studies are needed to validate the effects of
      carvone.

PMID- 27876338
TI  - Should you screen nursing home residents for cancer?
AB  - When considering screening for early cancer detection physicians should
      anticipate how they plan to follow up a screen detected cancer. Geriatric
      oncology research has developed validated functional assessments to estimate the
      balance of risk and benefit for treating cancers in the elderly. Robust elderly
      can benefit from treatment and therefore might benefit from screening. However
      the majority of elderly in long term residential care (LTC, or "the nursing
      home") would not benefit from cancer screening. The 1.4 million elderly people
      who reside in U.S. nursing homes represent the oldest and frailest segment of the
      aged population. On average, LTC residents have less than 5years estimated
      remaining life expectancy (RLE.) E.U. figures are similar. The majority have
      multiple functional deficits that would result in geriatric oncology screening
      scores in the frail range, at very high risk for severe toxicity from standard
      chemotherapy or extensive surgery. Therefore screening for asymptomatic cancer is
      not likely to benefit and has the potential to harm elderly nursing home
      residents.

PMID- 27876339
TI  - Diagnosis and treatment of Clostridium difficile (C. diff) colitis: Review of the
      literature and a perspective in gynecologic oncology.
AB  - Clostridium difficile infection (CDI) is a major cause of nosocomial diarrhea
      with the potential for significant morbidity and mortality. Colonization in a
      susceptible individual, with risk factors such as prior antibiotic use, advanced
      age, or medical comorbidities, may result in symptomatic infection. Although
      patients with a gynecologic malignancy may be at a higher risk of developing CDI
      due to an increased likelihood of having one or more risk factors, data do not
      consistently support the idea that chemotherapy or cancer itself are
      independently associated with CDI. For diagnosis of CDI, we recommended using a
      multi-step approach, with a highly sensitive initial rapid test such as the
      enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH) or nucleic acid
      amplification testing (NAAT), followed by confirmatory testing with of the above
      two tests or EIA toxin A/B, which has high specificity. Treatment varies based on
      the severity of disease. We recommend vancomycin as first-line therapy for an
      initial episode of mild/moderate or severe CDI, with consideration of fidaxomicin
      for patients at particularly high risk for recurrence. Rectal vancomycin may play
      an adjunctive role for some severe cases, while surgical intervention is
      indicated for fulminant CDI if no improvement six or more days after initiating
      medical therapy. For non-severe recurrent disease, the initial treatment regimen
      should be repeated, while subsequent episodes are more appropriately treated with
      a tapered and pulsed dose of vancomycin, fidaxomicin, or fecal microbiota
      transplantation.

PMID- 27876340
TI  - [Repply to the letter of Cherro-Farro et al.]

PMID- 27876341
TI  - Imaging of neuroendocrine tumors of the pancreas.
AB  - Pancreatic neuroendocrine tumors (PNETs) are rare and represent a heterogeneous
      disease. PNET can be functioning or non-functioning with different clinical
      presentations and different prognosis based on WHO and pTNM classifications. The
      role of imaging includes the localization of small functioning tumor,
      differentiation of these tumors from adenocarcinoma, identification of signs of
      malignancy and evaluation of extent. PNETs have a broad spectrum of appearance.
      On CT and MRI, most of functioning PNETs are well defined small tumors with
      intense and homogeneous enhancement on arterial and portal phases. However, some
      PNETs with a more fibrous content may have a more delayed enhancement that is
      best depicted on the delayed phase. Other PNETs can present as purely cystic,
      complex cystic and solid tumors and calcified tumors. Non-functioning PNETs are
      larger with less intense and more heterogeneous enhancement. Functional imaging
      is useful for disease staging, to detect disease recurrence or the primary but
      also to select patient candidate for peptide receptor radiometabolic treatment.
      Somatostatin receptor scintigraphy (SRS) (Octreoscan(r)) is still the most
      available technique. Gallium 68-SST analogue PET have been demonstrated to be
      more sensitive than SRS-SPEC and it will be the future of functional imaging for
      NET. Finally, 18FDG PET/CT is indicated for more aggressive PNET as defined
      either by negative SRS and huge tumor burden or ki67 above 10% or poorly
      differentiated PNEC tumors.

PMID- 27876342
TI  - Omega-3 fatty acids supplementation improves endothelial function and arterial
      stiffness in hypertensive patients with hypertriglyceridemia and high
      cardiovascular risk.
AB  - Association between hypertriglyceridemia and cardiovascular (CV) disease is still
      controversial. The purpose of this study was to compare omega-3 and ciprofibrate
      effects on the vascular structure and function in low and high CV risk
      hypertensive patients with hypertriglyceridemia. Twenty-nine adults with
      triglycerides 150-499 mg/dL were divided into low (<7.5%) and high (>=7.5%) CV
      risk, randomized to receive omega-3 fatty acids 1800 mg/d or ciprofibrate 100
      mg/d for 12 weeks. Treatment was switched after 8-week washout. Clinical
      evaluation and vascular tests were assessed at baseline and after intervention.
      Peripheral (131 +/- 3 to 125 +/- 3 mm Hg, P < .05) and aortic (124 +/- 3 to 118
      +/- 2 mg/dL, P < .05) systolic blood pressure were decreased by ciprofibrate in
      low-risk patients. In high-risk patients, pulse wave velocity was reduced (10.4
      +/- 0.4 to 9.4 +/- 0.3 m/s, P < .05) and flow-mediated dilation was increased
      (11.1 +/- 1.6 to 13.5 +/- 1.2%, P < .05) by omega-3. In conclusion, omega-3
      improved arterial stiffness and endothelial function, pointing out the beneficial
      effect of this therapy on vascular aging, in high-risk patients.

PMID- 27876343
TI  - Implications of the idea of neurodiversity for understanding the origins of
      developmental disorders.
AB  - Neurodiversity, a term initially used mostly by civil and human rights movements
      since the 1990s, refers to the notion that cognitive as well as emotional
      properties characteristic of developmental disorders such as autism spectrum
      disorders (ASD) are not necessarily deficits, but fall within normal behavioural
      variations exhibited by humans. The purpose of the present article is to examine
      the relevance of this notion to scientific research on ASD. On the assumption
      that one crucial survival advantage of intelligent activity is vigilance toward
      dangers in the external world, and such vigilance must work in the social domain
      as well as in the non-social domain, the author argues that the pattern of
      operation of an individual person's mind can be categorized according to the
      domain toward which that individual is more oriented. Individuals with ASD,
      overall, do not rely upon their social relationships but rather are predisposed
      to process perceived non-social objects in more depth, which manifests itself as
      hyper-sensation and hyper-attention to detail. It can be assumed that
      underconnectivity among cortical areas and subcortical areas underlies such
      mental operation neurologically. One of the main predictions based on this
      assumption is that all facets of psychological function are susceptible to
      disruption in ASD. Indeed, it has traditionally been thought that there are such
      general deficits in this disorder. However, contrary to the prevalent belief that
      people with ASD lack empathy, in fact people with ASD are capable of empathizing
      with the minds of others if those others are people with ASD. Thus, the
      neurological underconnectivity in ASD certainly leads some processing of
      information in the mind to work with less coordination, but has in fact
      contributed to providing Homo sapiens with behavioural variants. Finally, the
      clinical implications of the advantages of viewing ASD as a variation in
      neurodiversity are discussed.

PMID- 27876344
TI  - Bridging physics and biology: Reply to comments on "Phase separation driven by
      density-dependent movement: A novel mechanism for ecological patterns".

PMID- 27876346
TI  - WITHDRAWN: 45th Annual meeting of the European Teratology Society.
AB  - This article has been withdrawn at the request of the 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- 27876345
TI  - The reasonable effectiveness of agent-based simulations in evolutionary game
      theory: Reply to comments on "Evolutionary game theory using agent-based
      methods".

PMID- 27876347
TI  - Improved conventional and microwave-assisted silylation protocols for
      simultaneous gas chromatographic determination of tocopherols and sterols: Method
      development and multi-response optimization.
AB  - This paper reports on improved conventional thermal silylation (CTS) and
      microwave-assisted silylation (MAS) methods for simultaneous determination of
      tocopherols and sterols by gas chromatography. Reaction parameters in each of the
      methods developed were systematically optimized using a full factorial design
      followed by a central composite design. Initially, experimental conditions for
      CTS were optimized using a block heater. Further, a rapid MAS was developed and
      optimized. To understand microwave heating mechanisms, MAS was optimized by two
      distinct modes of microwave heating: temperature-controlled MAS and power
      controlled MAS, using dedicated instruments where reaction temperature and
      microwave power level were controlled and monitored online. Developed methods:
      were compared with routine overnight derivatization. On a comprehensive level,
      while both CTS and MAS were found to be efficient derivatization techniques, MAS
      significantly reduced the reaction time. The optimal derivatization temperature
      and time for CTS found to be 55 degrees C and 54min, while it was 87 degrees C
      and 1.2min for temperature-controlled MAS. Further, a microwave power of 300W and
      a derivatization time 0.5min found to be optimal for power-controlled MAS. The
      use of an appropriate derivatization solvent, such as pyridine, was found to be
      critical for the successful determination. Catalysts, like potassium acetate and
      4-dimethylaminopyridine, enhanced the efficiency slightly. The developed methods
      showed excellent analytical performance in terms of linearity, accuracy and
      precision.

PMID- 27876348
TI  - Characterization of an immobilized enzyme reactor for on-line protein digestion.
AB  - Despite the developments for faster liquid chromatographic and mass spectral
      detection techniques, the standard in-solution protein digestion for proteomic
      analyses has remained relatively unchanged. The typical in-solution trypsin
      protein digestion is usually the slowest part of the workflow, albeit one of the
      most important. The development of a highly efficient immobilized enzyme reactor
      (IMER) with rapid performance for on-line protein digestion would greatly
      decrease the analysis time involved in a proteomic workflow. Presented here is
      the development of a silica based IMER for on-line protein digestion, which
      produced rapid digestions in the presence of organic mobile phase for both model
      proteins and a complex sample consisting of the insoluble portion of a yeast cell
      lysate. Protein sequence coverage and identifications evaluated between the IMER
      and in-solution digestions were comparable. Overall, for a yeast cell lysate with
      only a 10s volumetric residence time on-column, the IMER identified 507 proteins
      while the in-solution digestion identified 490. There were no significant
      differences observed based on identified protein's molecular weight or
      isoelectric point between the two digestion methods. Implementation of the IMER
      into the proteomic workflow provided similar protein identification results,
      automation for sample analysis, and reduced the analysis time by 15h.

PMID- 27876350
TI  - A solution to the vessel shortage during free vascularized fibular grafting for
      reconstructing infected bone defects of the femur: Bridging with vein
      transplantation.
AB  - PURPOSE: The present study aimed to evaluate the feasibility and clinical
      efficacy of bridging vein transplantation to deal with the vessel shortage during
      free vascularized fibular grafting for reconstructing infected bone defects of
      the femur. METHODS: Twelve patients (aged 15-58 years) with infected bone defects
      of the femur (between 6.0 and 18.0cm) were recruited in this study. Vacuum
      sealing drainage were applied after extensive debridement of the infected bone
      defects and irrigated with 0.9% sodium chloride solution for 1-2 weeks. After the
      drainage was clear and the focal infections were controlled, the free
      vascularized fibula was harvested for reconstructing the femoral bone defects.
      The vascularized fibula was grafted and fixated appropriately at the recipient
      site. The autogenous great saphenous vein was harvested, one end was anastomosed
      and bridged the vascular pedicles of the fibular grafts, and the other end
      anastomosed the artery and/or the vein in the recipient healthy site. RESULTS:
      Mean length of vein transplantation with vascularized fibular graft was 10.2 cm
      (range 7-15cm). All patients had good radiological healing without recorded
      nonunion or malunion. No patient developed deep infection or implant failure.
      Primary bone healing was achieved in 10 patients; however, 2 grafted fibular
      formed pseudarthrosis with the recipient femoral and then healed after a
      secondary surgery. One patient suffered from graft stress fracture after bone
      healing and healed after external fixation. After the mean follow-up of 30 months
      (9-72 months), according to the Enneking scoring system, clinical outcomes were
      excellent in 7 patients, good in 4 and fair in one. The functional recovery rate
      of the lesion limb was 89.4%. CONCLUSIONS: Free vascularized fibular graft with
      vein transplantation bridged vascular pedicle can effectively repair the infected
      bone, improve blood supply to the bone defect site, and help control infection.
      It is a feasible and effective treatment for infected bone defects of the femur
      with poor soft tissue conditions, or blood supply vessel shortage.

PMID- 27876349
TI  - Morphological study on the pressure ulcer-like dermal lesions formed in the rat
      heel skin after transection of the sciatic nerves.
AB  - Due to transection of bilateral sciatic nerves, pressure ulcer-like dermal lesion
      occurred in the hairy skin covering of the heel skin in almost all rats. In the
      present study, chronological changes of the rat heel skin after the transection
      were morphologically and immunohistochemically examined. In the heel skin,
      redness and swelling began by 3days after the operation, and open wound formed by
      17days. At the redness and swelling stage, edema extensively occurred in the
      dermis. At the thickening stage, the epidermis at the pressed site became
      transiently thicker, and at the whitening stage, rapidly thinner. At these
      stages, the epidermis in the skin surrounding the pressed site became gradually
      thicker. At the yellow scar stage, the skin was covered only by necrotic tissues
      and horny layer. These layers were scratched during walking and turning, and the
      yellow scar stage became the open wound stage. Inflammatory reaction began at the
      thickening stage, and at the yellow scar and open wound stages, necrosis,
      infiltration of inflammatory cells and dilation of small blood vessels were
      observed. These morphological features are quite similar to those in the human
      pressure ulcer. These findings suggest that these dermal injuries could compare
      the human pressure ulcer for medical treatment and depressurization in future
      study.

PMID- 27876351
TI  - Inflammation in Schizophrenia: What It Means and How to Treat It.

PMID- 27876352
TI  - Quantitative analysis of pharmacokinetic profiles of verapamil and drug-drug
      interactions induced by a CYP inhibitor using a stable isotope-labeled compound.
AB  - The purpose of the present study is to demonstrate a useful approach (isotope-IV
      method) for analyzing drug-drug interactions (DDIs) following the oral
      administration of drugs using stable isotope-labeled compounds. Verapamil
      hydrochloride (VER) was used as a drug model. Deuterium-labeled VER (VER-d6,
      0.005 mg/kg) was intravenously administered to rats with or without a pre
      treatment with 1-aminobenzotriazole (ABT, 100 mg/kg), a potent CYP inhibitor, 1.5
      h after the oral administration of VER (1 mg/kg). PK parameters such as AUCpo,
      AUCiv, and CLtot were evaluated after the oral and intravenous administration of
      VER from the plasma concentration-time profiles of VER and VER-d6 in each rat.
      The oral bioavailability (F) of VER in rats was calculated as 0.02 +/- 0.01 and
      was significantly increased to 0.45 +/- 0.24 by the pre-treatment with ABT.
      Further PK analyses revealed that CYP-mediated metabolism was more strongly
      inhibited by ABT in the intestine (Fg) than in the liver (Fh). These results were
      consistent with those obtained using the conventional method in which oral and
      intravenous administration studies were performed using different rat groups.
      Therefore, the isotope-IV method is effective for performing PK analyses
      including DDIs after the oral administration of drugs.

PMID- 27876354
TI  - Update in the genetics of thalassemia: What clinicians need to know.
AB  - Thalassemia is a significant health problem worldwide. Prenatal diagnosis is the
      only effective way to prevent the birth of a fetus with severe thalassemias,
      which include hemoglobin Bart's hydrops fetalis and thalassemia major. However,
      accurate prenatal diagnosis depends on the comprehensive consideration of the
      molecular basis of thalassemias. To make a correct decision, the obstetrician
      should have a certain understanding of the genetics of thalassemias. Here we
      present a brief introduction of some fundamental genetic knowledge of
      thalassemias, including the production of hemoglobin, structure and location of
      globin genes, hemoglobin switch, epidemiology, clinical classification, molecular
      and cellular pathology, genotype-phenotype correlation, and genetic modifiers.
      Furthermore, some unusual clinical cases that cannot be explained by Mendel's
      laws are described. On the basis of a thorough understanding of the above
      information, clinicians should have the ability to precisely diagnose thalassemia
      patients and provide applicable genetic counselling to the affected families.

PMID- 27876353
TI  - Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin
      Regeneration: A Randomized Phase I/II Clinical Trial.
AB  - BACKGROUND: Mechanical stretch, in term of skin expansion, can induce effective
      but limited in vivo skin regeneration for complex skin defect reconstruction. We
      propose a strategy to obtain regenerated skin by combining autologous stem cell
      transplantation with mechanical stretch. METHODS: This randomized, blinded
      placebo-controlled trial enrolled 38 adult patients undergoing skin expansion
      presenting with signs of exhausted regenerative capacity. Patients randomly
      received autologous bone marrow mononuclear cell (MNC) or placebo injections
      intradermally. Follow-up examinations were at 4, 8weeks and 2years. The primary
      endpoint was the volume achieved in relation to the designed size of the expander
      (expansion index, EI). Secondary endpoints were surface area, thickness and
      texture of expanded skin. This trial is registered with ClinicalTrial.gov,
      NCT01209611. FINDINGS: The MNC group had a significantly higher EI at 4weeks
      (mean difference 0.59 [95% CI, 0.03-1.16]; p=0.039) and 8weeks (1.05 [95% CI,
      0.45-1.66]; p=0.001) versus controls. At 8weeks, the MNC group had significantly
      thicker skin (epidermis: p<0.001, dermis: p<0.001) and higher subjective scores
      for skin quality/texture (24.8 [95% CI, 17.6-32.1]; p<0.001). The MNC group had
      more skin surface area (70.34cm2 [95% CI, 39.75-100.92]; p<0.001). Patients in
      the MNC group gained up to the quadrupled surface area of expanded skin compared
      to pre-expansion at the end of expansion. No severe adverse events occurred.
      INTERPRETATION: Intradermal transplantation of autologous stem cells represents a
      safe and effective strategy to promote in vivo mechanical stretch induced skin
      regeneration, which can provide complex skin defect reconstruction with plentiful
      of tissue.

PMID- 27876355
TI  - Lung-protective ventilatory strategies in intubated preterm neonates with RDS.
AB  - This article provides a narrative review of lung-protective ventilatory
      strategies (LPVS) in intubated preterm infants with RDS. A description of
      strategies is followed by results on short-and long-term respiratory and
      neurodevelopmental outcomes. Strategies will include patient-triggered or
      synchronized ventilation, volume targeted ventilation, the technique of
      intubation, surfactant administration and rapid extubation to NCPAP (INSURE), the
      open lung concept, strategies of high-frequency ventilation, and permissive
      hypercapnia. Based on this review single recommendations on optimal LPVS cannot
      be made. Combinations of several strategies, individually applied, most probably
      minimize or avoid potential serious respiratory and cerebral complications like
      bronchopulmonary dysplasia and cerebral palsy.

PMID- 27876357
TI  - Building a New Field of Computational Psychiatry.

PMID- 27876356
TI  - [Low flux dialysate daily home hemodialysis: A result for the 62 first French and
      Belgian patients].
AB  - Since 2011, a new device is available for low flux dialysate quotidian home
      hemodialysis in France and Belgium. This study aims to evaluate the
      characteristics and dialysis prescriptions for Nx Stage System OneTM users. We
      retrospectively included patients trained between 2011 and 2013 in France and
      Belgium. We collected data concerning their clinical features, their dialysis
      prescriptions, their laboratory parameters until 6 months of dialysis and, reason
      for dropping in case of cessation. Sixty-two patients from 31 centers, aged 48+/
      18 years old, with a sex ratio 46/16 (M/F) are included with a median Charlson
      comorbidity index of 1 [0-3]. Of these patients, 71% are anuric and have been on
      dialysis for a mean time of 136.6+/-125 months. Previously, most of them had been
      taken care of in satellite units of dialysis (45%) and 14% are incident patients.
      In total, A total of 60% have an arterio-veinous fistula (AVF), with 18 patients
      using the Buttonhole system and 2 patients have a tunneled catheter. Median time
      for training was 26.5 days (17-45). Among the patients, 69% are dialyzed 6 days a
      week, during a mean time of 142.5+/-20 minutes with a volume of 20.9+/-3 liters
      of dialysate and without anticoagulant (63%). Predialytic levels of hemoglobin,
      creatinin, urea, phosphorus and beta2microglobulin remain stable. On the
      contrary, there is a significant improvement of albumin and bicarbonate levels.
      Technique survival was 75% at 1 year, and major reason for cessation was kidney
      transplant. It seems that this device fits for young patients, with few
      comorbidities and a long past in renal chronic failure. These results suggest
      that dialysis adequacy is acceptable despite low dialysate volumes but need
      confirmation with a longer follow up and a larger cohort.

PMID- 27876359
TI  - Somatoautonomic reflexes in acupuncture therapy: A review.
AB  - Oriental therapies such as acupuncture, moxibustion, or Anma, have been used to
      treat visceral disorders since ancient times. In each of these therapies,
      stimulation of the skin or underlying muscles leads to excitation of afferent
      nerves. The sensory information is carried to the central nervous system, where
      it is transferred to autonomic efferents, thus affecting visceral functions. This
      neuronal pathway, known as the "somatoautonomic reflex", has been systematically
      studied by Sato and his colleagues for over a half century. Nearly all their
      studies were conducted in anesthetized animals, whereas human patients are
      conscious. Responses in patients or the events following therapeutic somatic
      stimulation may differ from those observed in anesthetized animals. In fact, it
      is increasingly apparent that the responses in patients and animals are not
      always coincident, and the differences have been difficult for clinicians to
      reconcile. We review the mechanism of the "somatoautonomic reflex" as described
      in anesthetized animals and then discuss how it can be applied clinically.

PMID- 27876358
TI  - A randomized double-blind trial of intravenous immunoglobulin for bullous
      pemphigoid.
AB  - BACKGROUND: Patients with steroid-resistant bullous pemphigoid (BP) require an
      appropriate treatment option. OBJECTIVE: A multicenter, randomized, placebo
      controlled, double-blind trial was conducted to investigate the therapeutic
      effect of high-dose intravenous immunoglobulin (IVIG; 400mg/kg/day for 5days) in
      BP patients who showed no symptomatic improvement with prednisolone
      (>=0.4mg/kg/day) administered. METHODS: We evaluated the efficacy using the
      disease activity score on day15 (DAS15) as a primary endpoint, and changes in the
      DAS over time, the anti-BP180 antibody titer, and safety for a period of 57days
      as secondary endpoints. RESULTS: We enrolled 56 patients in this study. The DAS15
      was 12.5 points lower in the IVIG group than in the placebo group (p=0.089). The
      mean DAS of the IVIG group was constantly lower than that of the placebo group
      throughout the course of observation, and a post hoc analysis of covariance
      revealed a significant difference (p=0.041). Furthermore, when analyzed only in
      severe cases (DAS>=40), the DAS15 differed significantly (p=0.046). The anti
      BP180 antibody titers showed no difference between the two groups. CONCLUSION:
      IVIG provides a beneficial therapeutic outcome for patients with BP who are
      resistant to steroid therapy.

PMID- 27876360
TI  - The role of high density lipoprotein in Type 1 Gaucher disease.
AB  - Type I Gaucher Disease (GD1) is known to be associated with hypocholesterolemia
      and reduced levels of low density lipoprotein (LDL) and high density lipoprotein
      (HDL). In this study we aimed to correlate disease severity with HDL levels and
      to evaluate the effect of enzyme replacement therapy (ERT) on HDL levels as well
      as estimating the frequency of cardiovascular events in GD. Two groups of GD1
      patients were evaluated: 30 untreated and 36 patients on ERT. Disease severity,
      biomarkers of GD and lipid levels were evaluated in the two groups. The Zimran
      Severity Score Index (SSI) was used to estimate disease severity and the effect
      of ERT on HDL levels was evaluated, as well as the frequency of cardiovascular
      disease. GD1 patients with more severe disease (SSI median 11) had significantly
      lower levels of HDL (median 23mg/dL), compared to patients with milder (SSI
      median 4.5) disease (median 37mg/dL p=0.001). HDL levels increased after ERT.
      Despite lower HDL levels in patients with more severe disease, a low frequency of
      cardiovascular events was detected. HDL level should be used in GD as a biomarker
      for diagnosis, monitoring and estimation of ERT effect.

PMID- 27876361
TI  - Beneficial effects of Galectin-9 on allergen-specific sublingual immunotherapy in
      a Dermatophagoides farinae-induced mouse model of chronic asthma.
AB  - BACKGROUND: Allergen-specific sublingual immunotherapy is a potential disease
      modifying treatment for allergic asthma. Galectin-9 (Gal-9), a beta-galactoside
      binding protein with various biologic effects, acts as an immunomodulator in
      excessive immunologic reactions by expanding regulatory T cells (Treg) and
      enhancing transforming growth factor (TGF)-beta signaling. We investigated the
      efficacy of sublingually administered Gal-9 as an adjuvant to a specific allergen
      in a Dermatophagoides farinae (Df)-induced mouse model of chronic asthma.
      METHODS: BALB/c mice were intranasally sensitized with Df extract 5 days/week for
      5 weeks, and then sublingual Df-allergen extract for 2 weeks (5 days/week). Three
      days after the final sublingual treatment, mice were intranasally challenged with
      Df extract. The early asthmatic response (EAR) was evaluated 5 min after the last
      Df challenge. Airway hyperresponsiveness (AHR) was assayed and bronchoalveolar
      lavage (BAL) was performed 24 h after the last allergen challenge. Serum IgE and
      cytokine levels, and number of inflammatory cells in the BAL fluid (BALF) were
      analyzed. RESULTS: Sublingual Df treatment in the presence of Gal-9, but not
      alone, significantly reduced AHR; EAR; number of eosinophils and interleukin-13
      in the BALF; and serum IgE levels. BALF TGF-beta1 levels were significantly
      increased in the presence of Gal-9 compared with Df alone. Treg depletion blocked
      the inhibitory effects of Gal-9 on the EAR, AHR, eosinophilic airway
      inflammation, and Df-specific serum IgE levels, and suppressed BALF TGF-beta1
      levels. CONCLUSIONS: Gal-9 exhibited beneficial effects of sublingual Df allergen
      specific immunotherapy in a Df-induced mouse model of chronic asthma, possibly by
      Gal-9-induced TGF-beta1 production in the lung.

PMID- 27876362
TI  - Boxer's elbow: internal impingement of the coronoid and olecranon process. A
      report of seven cases.
AB  - BACKGROUND: Boxer's elbow has been described in the literature as an extension
      and hyperextension injury. However, in our experience, there is a coexisting
      impingement lesion in the anterior compartment of the elbow that has not
      previously been described. We report a series of professional boxers with elbow
      disease treated arthroscopically. The aim of the paper was to accurately describe
      the pathoanatomy of the condition, the key points in its diagnosis, and the
      outcomes of surgical treatment. METHODS: Seven professional boxers were treated
      for symptomatic elbow disease. Clinical evaluation included range of motion and
      Disabilities of the Arm, Shoulder, and Hand score. The arthroscopic findings and
      procedures were documented. RESULTS: Symptoms were mainly those of anterior and
      posterior impingement; 6 elbows had an anterior impingement lesion and 6 had a
      posterior impingement lesion. Postoperatively, the mean Disabilities of the Arm,
      Shoulder, and Hand score was 2.7 (range, 0-13.3) at a median of 15 (range, 6-36)
      months postoperatively. All boxers returned to their previous level of
      competition and 5 won their next bout. All of the boxers used an orthodox stance,
      and in all but 1 case the left elbow was the pathologic elbow. CONCLUSION: Boxers
      are prone to development of anterior and posterior elbow impingement. The side of
      the pathologic process is related to the boxer's stance, with the lead arm being
      more vulnerable. Arthroscopic debridement is an effective treatment, enabling
      return to a high competitive level. Surgeons, sports medicine physicians, and
      physiotherapists should be aware of the condition.

PMID- 27876364
TI  - Editorial.

PMID- 27876363
TI  - Understanding the effects of past flood events and perceived and estimated flood
      risks on individuals' voluntary flood insurance purchase behavior.
AB  - Over the past several decades, the economic damage from flooding in the coastal
      areas has greatly increased due to rapid coastal development coupled with
      possible climate change impacts. One effective way to mitigate excessive economic
      losses from flooding is to purchase flood insurance. Only a minority of coastal
      residents however have taken this preventive measure. Using original survey data
      for all coastal counties of the United States Gulf Coast merged with contextual
      data, this study examines the effects of external influences and perceptions of
      flood-related risks on individuals' voluntary behaviors to purchase flood
      insurance. It is found that the estimated flood hazard conveyed through the U.S.
      Federal Emergency Management Agency's (FEMA's) flood maps, the intensities and
      consequences of past storms and flooding events, and perceived flood-related
      risks significantly affect individual's voluntary purchase of flood insurance.
      This behavior is also influenced by home ownership, trust in local government,
      education, and income. These findings have several important policy implications.
      First, FEMA's flood maps have been effective in conveying local flood risks to
      coastal residents, and correspondingly influencing their decisions to voluntarily
      seek flood insurance in the U.S. Gulf Coast. Flood maps therefore should be
      updated frequently to reflect timely and accurate information about flood
      hazards. Second, policy makers should design strategies to increase homeowners'
      trust in the local government, to better communicate flood risks with residents,
      to address the affordability issue for the low-income, and better inform less
      educated homeowners through various educational programs. Future studies should
      examine the voluntary flood insurance behavior across countries that are
      vulnerable to flooding.

PMID- 27876365
TI  - Midyear Commentary on Trends in Drug Delivery and Clinical Translational
      Medicine: Growth in Biosimilar (Complex Injectable Drug Formulation) Products
      Within Evolving Collaborative Regulatory Interagency (FDA, FTC, and DOJ)
      Practices and Enforcement.
AB  - Before the 2009 Biologics Price Competition and Innovation Act that enabled the
      U.S. Federal Drug Administration (FDA) to create the 351(k) Biologic License
      Application-an abbreviated biosimilar approval process, FDA approved follow-on
      biomolecule products such as beta-interferon, glucagon, hyaluronidase, and
      somatropin (human growth hormone) under varying and evolving rules. With the
      351(k) Biologic License Application biosimilar approval process in place,
      currently, there are 4 (licensed in 2015-2016) biosimilars available, namely
      Neupogen (filgrastim; $1 B/y), Humira (adalumumab; $14.2 B/y), Enbrel
      (etanercept; $8.7 B/y), and Remicade (infliximab; $6.5 B/y). With well
      established product market capitalization of these and other top income producers
      such as Rituxan (rituximab; $6.8 B/y), Herceptin (trastuzumab; $6.5 B/y), and
      Avastin (bevacizumab; $5.8 B/y), and a price differential of 15%-30% compared to
      branded products, there is an intense interest in development of biosimilars by
      established pharmaceutical companies. Currently, there are 160 biosimilar
      candidates in clinical studies, many of which are sponsored by large
      pharmaceutical companies known for product innovation. This trend will likely
      continue. Additional information on a biomolecule platform is presented in the
      Journal of Pharmaceutical Sciences Drug Delivery Clinical Trials Database
      (jpharmscidatabase.org). There are 44,789, 18,456, and 12,897 clinical trials
      registered to evaluate (1) drug delivery technology, (2) biomolecule platform,
      and (3) drug metabolism and pharmacokinetic-pharmacodynamic interactions;
      representing 19%-60% increase over the last 3 years.

PMID- 27876366
TI  - Leishmania amazonensis infection induces behavioral alterations and modulates
      cytokine and neurotrophin production in the murine cerebral cortex.
AB  - Neurological symptoms have been associated with Leishmania infection, however
      little is known about how the nervous system is affected in leishmaniasis. This
      work aimed to analyze parasitic load, production of cytokines/neurotrophins in
      the prefrontal cortex and behavioral changes in BALB/c mice infected with
      Leishmania amazonensis. At 2 and 4months post-infection, infected mice showed a
      decrease in IFN-gamma, IL-1, IL-6, IL-4, IL-10 cytokines and BDNF and NGF
      neurotrophins in prefrontal cortex associated with increased anxiety behavior.
      Parasite DNA was found in brain of all animals at 4months post-infection, when
      the levels of IBA-1 (activated macrophage/microglia marker) and TNF-alpha was
      increased in the prefrontal cortex. However TNF-alpha returned to normal levels
      at 6months post-infection suggesting a neuroprotective mechanism.

PMID- 27876367
TI  - Factors contributing to postpartum blood-loss in low-risk mothers through
      expectant management in Japanese birth centres.
AB  - OBJECTIVE: To describe aspects of expectant midwifery care for low-risk women
      conducted in midwifery-managed birth centres during the first two critical hours
      after delivery and to compare differences between midwifery care, client factors
      and postpartum blood loss volume. METHOD: As a secondary analysis from a larger
      study, this descriptive retrospective study examined data from birth records of
      4051 women who birthed from 2001 to 2006 at nine (21%) of the 43 midwifery
      centres in Tokyo. Nonparametric and parametric analyses identified factors
      related to increased blood loss. Interviews to establish sequence of midwifery
      care were conducted. FINDINGS: The midwifery centres provided care based on
      expectant management principles from birth to after expulsion of the placenta.
      Approximately 63.3% of women were within the normal limits of blood loss volume
      under 500g. A minority of women (12.9%) experienced blood loss between 500 and
      800g and 4% had blood loss exceeding 1000g. Blood loss volume tended to increase
      with infant birth weight and duration of delivery. The total blood loss volume
      was significantly higher for primiparas than for multiparas during the critical
      two hours after delivery and for immediately after delivery, yet blood loss
      volume was significantly higher for multiparas than for primiparas during the
      first hour after delivery. Preventive uterine massage and umbilical cord clamping
      after placenta expulsion resulted in statistically significant less blood loss.
      Identified were two patterns of midwifery care based on expectant management
      principles from birth to after expulsion of the placenta. The practice of
      expectant management was not a significant factor for increased postpartum blood
      loss. CONCLUSION: These results detail specific midwifery practices and highlight
      the clinical significance of expectant management with low risk pregnant women
      experiencing a normal delivery.

PMID- 27876370
TI  - Non-linear rotation-free shell finite-element models for aortic heart valves.
AB  - Hyperelastic material models have been incorporated in the rotation-free, large
      deformation, shell finite element (FE) formulation of (Stolarski et al., 2013)
      and applied to dynamic simulations of aortic heart valve. Two models used in the
      past in analysis of such problem i.e. the Saint-Venant and May-Newmann-Yin (MNY)
      material models have been considered and compared. Uniaxial tests for those
      constitutive equations were performed to verify the formulation and
      implementation of the models. The issue of leaflets interactions during the
      closing of the heart valve at the end of systole is considered. The critical role
      of using non-linear anisotropic model for proper dynamic response of the heart
      valve especially during the closing phase is demonstrated quantitatively. This
      work contributes an efficient FE framework for simulating biological tissues and
      paves the way for high-fidelity flow structure interaction simulations of native
      and bioprosthetic aortic heart valves.

PMID- 27876368
TI  - Biomechanics and biorheology of red blood cells in sickle cell anemia.
AB  - Sickle cell anemia (SCA) is an inherited blood disorder that causes painful
      crises due to vaso-occlusion of small blood vessels. The primary cause of the
      clinical phenotype of SCA is the intracellular polymerization of sickle
      hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated
      conditions. In this review, we discuss the biomechanical and biorheological
      characteristics of sickle RBCs and sickle blood as well as their implications
      toward a better understanding of the pathophysiology and pathogenesis of SCA.
      Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their
      specific contribution to vaso-occlusive crisis.

PMID- 27876369
TI  - Multi-component model of intramural hematoma.
AB  - A novel multi-component model is introduced for studying interaction between
      blood flow and deforming aortic wall with intramural hematoma (IMH). The aortic
      wall is simulated by a composite structure submodel representing material
      properties of the three main wall layers. The IMH is described by a
      poroelasticity submodel which takes into account both the pressure inside
      hematoma and its deformation. The submodel of the hematoma is fully coupled with
      the aortic submodel as well as with the submodel of the pulsatile blood flow.
      Model simulations are used to investigate the relation between the peak wall
      stress, hematoma thickness and permeability in patients of different age. The
      results indicate that an increase in hematoma thickness leads to larger wall
      stress, which is in agreement with clinical data. Further simulations demonstrate
      that a hematoma with smaller permeability results in larger wall stress,
      suggesting that blood coagulation in hematoma might increase its mechanical
      stability. This is in agreement with previous experimental observations of
      coagulation having a beneficial effect on the condition of a patient with the
      IMH.

PMID- 27876371
TI  - Approaches for treatment of aortic arch aneurysm, a numerical study.
AB  - Aortic arch aneurysm is a complex pathology which requires coverage of one or
      more aortic arch vessels. In this study we explore the hemodynamic behavior of
      the aortic arch in aneurysmatic and treated cases with three currently available
      treatment approaches: Surgery Graft, hybrid Stent-Graft and chimney Stent Graft.
      The analysis included four models of the time-dependent fluid domains of
      aneurysmatic arch and of the surgery, hybrid and chimney endovascular techniques.
      Dimensions of the models are based on typical anatomy, and boundary conditions
      are based on typical physiological flow. The simulations used computational fluid
      dynamics (CFD) methods to delineate the time-dependent flow dynamics in the four
      geometric models. Results of velocity vectors, flow patterns, blood pressure and
      wall shear stress distributions are presented. The results delineate disturbed
      and recirculating flow in the aortic arch aneurysm accompanied with low wall
      shear stress and velocities, compared to a uniformly directed flow and nominal
      wall shear stress (WSS) in the model of Surgery graft. Out of the two endograft
      procedures, the hybrid procedure clearly exhibits better hemodynamic performances
      over the chimney model, with lower WSS, lower pressure drop and less disturbed
      and vortical flow regions. Although the chimney procedure requires less
      manufacturing time and cost, it is associated with higher risk rates, and
      therefore, it is recommended only for emergency cases. This study may shed light
      on the hemodynamic factors for these complications and provide insight into ways
      to improve the procedure.

PMID- 27876372
TI  - Interannual variability of soft-bottom macrobenthic communities of the NW Gulf of
      Mexico in relationship to the Deepwater Horizon oil spill.
AB  - A 3-year research program was undertaken to assess potential environmental
      disturbance caused by the Deepwater Horizon oil spill to the soft-bottom
      macrobenthic communities within Mexican waters of the northwestern Gulf of
      Mexico. Community properties and temporal/spatial variability were analyzed
      besides toxicant parameters such as hydrocarbons and trace-metals. Overall
      infaunal density increased, taxa proportion changed, and small-size opportunistic
      organisms prevailed throughout the study. Annual abundance-biomass comparison
      (ABC) curves revealed progressive stress scenarios from moderate to severe.
      Concentrations of vanadium, nickel, cobalt, PAHs and AHs increased gradually over
      time. However, low correlations between benthic density and biogeochemical
      variables were determined. Initially, sedimentary properties were the main
      drivers of benthic community structure; subsequently, nickel, vanadium and PAHs,
      indicative of anthropogenic effect, were highlighted. Interannual variability in
      the macroinfauna was attributed to the synergy of several environmental factors.
      Undoubtedly, compounds derived from fossil fuels had a significant disturbance
      role, but their source remains uncertain.

PMID- 27876373
TI  - Bioaccumulation of heavy metals by shrimp (Litopenaeus schmitti): A dose-response
      approach for coastal resources management.
AB  - We reveal a dose-response relationship for bioaccumulation of Zn, Cu and Cr in
      shrimp Litopenaeus schmitti from Sepetiba Bay, Rio de Janeiro, Brazil. Our model
      estimates the current risk (AD50 was 70% of the legal limit) and the daily metal
      uptake rate for each metal. It can also evaluate the relative reliability of
      predictions for tissue concentrations reaching the legal limits for human
      consumption (approximately 1year) and predictions related to asymptotic length,
      arising from (i) direct regression of the metal concentration (MeC) versus total
      length (TL) and age (duration of exposure), and (ii) correlation of the
      incorporation rate (IR=MeC/TL) with age. Metal incorporation rates (IR), i.e. a
      kinetic proxy for absorption during growth up to attainment of asymptotic length,
      decrease with age, reflecting a slow-down in metal absorption. This pattern
      mitigates the high initial concentrations observed for juveniles.

PMID- 27876374
TI  - Characterizing light attenuation within Northwest Florida Estuaries: Implications
      for RESTORE Act water quality monitoring.
AB  - Water Quality (WQ) condition is based on ecosystem stressor indicators (e.g.
      water clarity) which are biogeochemically important and critical when considering
      the Deepwater Horizon oil spill restoration efforts under the 2012 RESTORE Act.
      Nearly all of the proposed RESTORE projects list restoring WC as a goal, but 90%
      neglect water clarity. Here, dynamics of optical constituents impacting clarity
      are presented from a 2009-2011 study within Pensacola, Choctawhatchee, St. Andrew
      and St. Joseph estuaries (targeted RESTORE sites) in Northwest Florida.
      Phytoplankton were the smallest contribution to total absorption (at-wPAR) at
      412nm (5-11%), whereas colored dissolved organic matter was the largest (61-79%).
      Estuarine at-wPAR was significantly related to light attenuation (KdPAR), where
      individual contributors to clarity and the influence of climatic events were
      discerned. Provided are conversion equations demonstrating interoperability of
      clarity indicators between traditional State-measured WQ measures (e.g. secchi
      disc), optical constituents, and even satellite remote sensing for obtaining
      baseline assessments.

PMID- 27876375
TI  - [Are there valid instruments? A necessary debate].

PMID- 27876376
TI  - Non-surgical and surgical interventions for airway obstruction in children with
      Robin Sequence.
AB  - There is widespread lack of consensus regarding treatment of airway obstruction
      in children with Robin Sequence. This study aimed to systematically summarize
      outcomes of non-surgical and surgical options to treat airway obstruction in
      children with Robin Sequence. The authors searched the Medline, EMBASE and
      CENTRAL databases. Studies primarily on mandibular distraction were excluded.
      Study quality was appraised with the Methodological Index for Non-Randomized
      Studies (MINORS) score. Forty-eight studies were included, of which 45 studies
      had a retrospective non-comparative set up, two studies had a prospective design
      and one study was a clinical trial. The mean MINORS score was 7.3 (range 3-10).
      The rates of successful relief of the airway obstruction (SRoAO) were: not
      available for orthodontic appliance (2 studies, n = 24), 67-100% for
      nasopharyngeal airway (6 studies, n = 126); 100 % for non-invasive respiratory
      support (2 studies, n = 12); 70-96% for tongue-lip adhesion (11 studies, n =
      277); 50-84% for subperiosteal release of the floor of the mouth (2 studies, n =
      47); 100% for mandibular traction (3 studies, n = 133); 100% for tracheostomy (1
      study, n = 25). The complication rate ranged from zero to 55%. Although SRoAO
      rates seemed comparable, high-level evidence remains scarce. Future research
      should include description of the definition, treatment indication, and objective
      outcomes.

PMID- 27876377
TI  - Quality of life in long-term oral cancer survivors: an 8-year prospective study
      in China.
AB  - OBJECTIVES: The purpose of the prospective study was to evaluate the long-term
      changes in quality of life (QOL) in patients with oral cancer and to examine the
      potential factors that predicted QOL at 8 years after treatment. STUDY DESIGN:
      Seventy-one patients were evaluated by the University of Washington quality of
      life scale. QOL in 30 long-term survivors was assessed at diagnosis and at the 3
      month, 1-year, and 8-year follow-up. RESULTS: QOL was found to be better among
      survivors compared with nonsurvivors at the 1-year follow-up. Levels of pain,
      mood, and anxiety showed clinically and statistically significant improvements
      between diagnosis and at 8 years following treatment, whereas problems with
      chewing, speech, shoulder mobility, and taste worsened during this interval (P <
      .05). From 1 to 8 years, patients reported clinically significant improvements
      with regard to appearance, recreation, speech, saliva, and anxiety. Among the 11
      sociodemographic, disease-, or treatment-related factors, age and tumor site were
      associated with long-term QOL. CONCLUSIONS: Although the QOL among patients with
      oral cancer was generally favorable in the long term, the changed patterns in
      different domains over time should be noted. Improved QOL between the 1-year and
      the 8-year follow-up demonstrated the dynamics of QOL after 1 year and justified
      ongoing follow-up beyond the 1-year observation point.

PMID- 27876379
TI  - MicroRNA profiling of human intermediate monocytes.
AB  - Among the three human monocyte subsets, intermediate CD14++CD16+ monocytes have
      been characterized as particularly proinflammatory cells in experimental studies
      and as potential biomarkers of cardiovascular risk in clinical cohorts. To
      further substantiate the distinct role of intermediate monocytes within human
      monocyte heterogeneity, we assessed subset-specific expression of miRNAs as
      central epigenetic regulators of gene expression. We hypothesized that
      intermediate monocytes have a distinct miRNA profile compared to classical and
      non-classical monocytes. By using small RNA-seq we analyzed 662 miRNAs in the
      three monocyte subsets. We identified 38 miRNAs that are differentially expressed
      in intermediate monocytes compared to both classical and non-classical monocytes
      with a p value of <10-10, of which two miRNAs - miR-6087 (upregulated) and miR
      150-5p (downregulated) - differed in their expression more than ten-fold. Pathway
      analysis of the 38 differentially expressed miRNAs linked intermediate monocytes
      to distinct biological processes such as gene regulation, cell differentiation,
      toll-like receptor signaling as well as antigen processing and presentation.
      Moreover, differentially expressed miRNAs were connected to those genes that we
      previously identified as markers of intermediate monocytes. In aggregation, we
      provide first genome-wide miRNA data in the context of monocyte heterogeneity,
      which substantiate the concept of monocyte trichotomy in human immunity. The
      identification of miRNAs that are specific for intermediate monocytes may allow
      to develop strategies, which particularly target this cell population while
      sparing the other two subsets.

PMID- 27876380
TI  - Laparoscopic complete mesocolic excision with central vascular ligation in 600
      right total mesocolectomies: Safety, prognostic factors and oncologic outcome.
AB  - BACKGROUND: To analyze our experience with laparoscopic right Mesocolectomy in
      right colonic cancers. METHODS: 600 consecutive patients were studied. RESULTS:
      Mortality was 0.5%; morbidity was 35.5%. Mean mesocolic area was 15339 +/- 1639
      mm3, specimen length 24.3 +/- 3.3 cm, distance from the tumor to high tie was 103
      +/- 6 mm and mean lymph nodes harvested was 27 +/- 3; mesocolic plane was
      achieved in 81% of cases. Survival was 83%; stratified survival in patients with
      stage II, IIIA/B and in the subgroup of stage IIIC patients with negative apical
      nodes was 88.7%, 72.4%, 71.4% respectively; stage IIIC patients with positive
      apical nodes showed poor survival (27.7%). Recurrence occurred in 177 patients
      (29.5%) and was mainly systemic (22.7%). At the multivariate analysis, "non
      mesocolic" plane of resection, positive N3 apical nodes and CEA levels >5 ng/dL
      were found to be independent prognostic factors. CONCLUSIONS: Laparoscopic right
      Mesocolectomy showed to be safe and yielded surgical specimens of high quality,
      with impact on survival; positive N3 apical nodes and "non mesocolic" planes were
      independently associated to poor outcome.

PMID- 27876378
TI  - Toxicities and dose-volume histogram parameters of MRI-based brachytherapy for
      cervical cancer.
AB  - PURPOSE: To analyze the toxicities and dose-volume histogram parameters of
      external-beam and magnetic resonance imaging-based intracavitary brachytherapy in
      cervical cancer patients. METHODS AND MATERIALS: Acute and late toxicities were
      assessed in 135 patients divided into four groups: group 1, grade 0; group 2,
      grades 1-4; group 3, grades 0-1; and group 4, grades 2-4. The doses at the
      International Commission on Radiation Units and Measurements (DICRU) and minimum
      doses to the most exposed 0.1, 1, 2, and 5 cc (D0.1cc, D1cc, D2cc, and D5cc) of
      normal organs were calculated as equivalent doses in 2 Gy (alpha/beta = 3).
      RESULTS: The median follow-up was 35.2 months. For rectum, DICRU, D0.1cc, D1cc,
      and D2cc were significantly different between groups 1 and 2 and DICRU, D0.1cc,
      and D1cc between groups 3 and 4. For bladder, D0.1cc, D1cc, and D2cc were
      significantly different between groups 1 and 2 and DICRU, D1cc, D2cc, and D5cc
      between groups 3 and 4. Grade 2-4 bladder toxicity occurred in fewer patients
      with D2cc <= 95 Gy than those with D2cc > 95 Gy (7% vs. 22%, p = 0.014).
      CONCLUSIONS: DICRU, D0.1cc, D1cc, and D2cc are relevant for predicting late
      rectal toxicities. The patients with bladder D2cc > 95 Gy are required to be in
      close observation for severe late toxicities.

PMID- 27876381
TI  - Re: Disorders of the lymphatic system of the abdomen. A reply.

PMID- 27876382
TI  - Amperometric triglyceride bionanosensor based on nanoparticles of lipase,
      glycerol kinase, glycerol-3-phosphate oxidase.
AB  - The nanoparticles (NPs) aggregates of lipase from porcine pancreas, glycerol
      kinase (GK) from Cellulomonas sp. and glycerol-3-phosphate oxidase (GPO) from
      Aerococcus viridanss were prepared by desolvation and glutaraldehyde crosslinking
      and functionalized by cysteamine. These enzyme nanoparticles (ENPs) were
      characterized by transmission electron microscopy (TEM) and Fourier transform
      infra red (FTIR) spectroscopy. The functionalzed ENPs aggregates were co
      immobilized covalently onto polycrystalline Au electrode through thiolated bond.
      An improved amperometric triglyceride (TG) bionanosensor was constructed using
      this ENPs modified Au electrode as working electrode. Biosensor showed optimum
      current at 1.2 V within 5s, at pH 6.5 and 35  degrees C.A linear relationship was
      obtained between current (mA) and triolein concentration in lower concentration
      range,10-100 mg/dL and higher concentration range, 100-500 mg/dL. Limit of
      detection (LOD) of bionanosensor was 1.0 MUg/ml. Percent analytical recovery of
      added trolein (50 and 100 mg/dL) in serum was 95.2 +/- 0.5 and 96.0 +/- 0.17.
      Within and between batch coefficients of variation (CV) were 2.33% and 2.15%
      respectively. A good correlation (R2 = 0.99) was obtained between TG values in
      sera measured by present biosensor and standard enzymic colorimetric method with
      the regression equation: y= (0.993x + 0.967). ENPs/Au electrode was used 180
      times over a period of 3 months with 50% loss in its initial activity, when
      stored dry at 4  degrees C.

PMID- 27876383
TI  - Helmet use and injury severity among pediatric skiers and snowboarders in
      Colorado.
AB  - INTRODUCTION: Skiing and snowboarding are popular winter recreational activities
      that are commonly associated with orthopedic type injuries. Unbeknownst to most
      parents, however, are the significant but poorly described risks for head,
      cervical spine and solid organ injuries. Although helmet use is not mandated for
      skiers and snowboarders outside of resort sponsored activities, we hypothesized
      that helmet use is associated with a lower risk of severe head injury, shorter
      ICU stay and shorter hospital length of stay. METHODS: The trauma registry at a
      level I pediatric trauma center in the state of Colorado was queried for children
      ages 3-17years, who sustained an injury while skiing or snowboarding from
      1/1/1999 to 12/31/2014. Injury severity was assessed by Abbreviated Injury
      Severity (AIS) score, injury severity score (ISS) and admission location. Head
      injury was broadly defined as any trauma to the body above the lower border of
      the mandible. Regression analysis was used to test associations of variables with
      injury severity. RESULTS: 549 children sustained snow sport related injuries
      during the 16year study period. The mean patient age was11+/-3years, most were
      male (74%) and the majority were Colorado residents (54%). The overall median ISS
      was 9 (IQR 4-9) and 78 children (14%) were admitted to the ICU. Colorado
      residents were nearly twice as likely to be wearing a helmet at the time of
      injury, compared to visitors from out-of-state (adjusted OR 1.86, 95% CI 1.24
      2.76, p=0.002). In a multivariate analysis injury severity was significantly
      associated with injury while skiing (p=0.026), helmet use (p=0.0416), and
      sustaining a head injury (p<0.0001). In a separate multivariate analysis ICU
      admission was associated with head injury (p<0.0001) and wearing a helmet
      (p=0.0257); however, those wearing a helmet and admitted to the ICU had
      significantly lower ISS (p=0.007) and head AIS (p=0.011) scores than those who
      were not wearing a helmet at the time of injury. CONCLUSION: Visitors from out of
      state were less likely to be wearing a helmet when injured and more likely to be
      severely injured, suggesting Colorado residents have a better understanding of
      the benefits of helmet usage. Helmeted skiers and snowboarders who were admitted
      to the ICU had significantly lower ISS and head AIS scores than those who were
      not helmeted. Pediatric skiers, snowboarders and their parents should be educated
      on the significant risks associated with these activities and the benefits of
      helmet usage. LEVEL OF EVIDENCE: III.

PMID- 27876384
TI  - Corrigendum to "Genetic and protein biomarkers in blood for the improved
      detection of GH abuse" [J. Pharm. Biomed. Anal. 128 (2016) 111-118, doi:
      10.1016/j.jpba.2016.05.022.].

PMID- 27876386
TI  - Future perspectives in the medical treatment of benign prostatic hyperplasia.

PMID- 27876387
TI  - Hydropeaking in regulated rivers - From process understanding to design of
      mitigation measures.

PMID- 27876388
TI  - Depth-related response of macroinvertebrates to the reversal of eutrophication in
      a Mediterranean lake: Implications for ecological assessment.
AB  - A better management of nutrient inflows into lakes has led to an improvement in
      their conditions (i.e. reversal of eutrophication) and the effects of this on
      macroinvertebrate communities that inhabit different lake-depth zones is largely
      unknown. This paper reports a comparison of macroinvertebrate communities living
      in the eulittoral, infralittoral and sublittoral/profundal zones of Lake Nemi
      (Central Italy) before and after its natural recovery from eutrophication
      following the deviation of domestic wastewater. The infralittoral zone responded
      more rapidly than the other two depth-zones to the improved ecological
      conditions, as shown by larger differences in community composition between the
      two periods. In the eulittoral sand, the combined effects of hydromorphological
      pressures and reversal of eutrophication hindered the biotic response. In the
      eulittoral and infralittoral zones, typical taxa of mesotrophic waters appeared
      or increased their abundances after the eutrophication reversal. Benthic
      invertebrate response was slower in the sublittoral/profundal zone due to
      deoxygenation that continued to prevail in the deepest area of the lake during
      summer. However, both tolerant and more sensitive taxa were collected there for
      the first time. After the reversal of eutrophication, the percentage of
      molluscan+large crustaceans increased in the infralittoral zone, whereas the
      oligochaete/chironomid ratio decreased in both sublittoral/profundal and
      infralittoral zones. Functional feeding metrics (percentages of filter-feeders,
      collector-gatherers, miners and scrapers/grazers) differently tracked the
      reversal of eutrophication in the three depth-zones probably according to the
      effects of the reduction of nutrients on food-web structure influencing
      macroinvertebrates. Biological Monitoring Working Party (BMWP) and the Average
      Score Per Taxon (ASPT) seemed to respond to eutrophication reversal only in the
      sublittoral/profundal zone, where deoxygenation plays a major role as a
      structuring agent of the community. Our results suggest that the effects of
      reversal of eutrophication can be better assessed by examining the response of
      the communities belonging to each zone individually.

PMID- 27876389
TI  - Dynamics in cyanobacterial communities from a relatively stable environment in an
      urbanised area (ambient springs in Central Poland).
AB  - Ambient springs are often cited as an example of an ecosystem with stable
      environmental conditions. A static biotope fosters the development of constant
      communities with a stable qualitative and relatively stable quantitative
      structure. Two years of studying cyanobacteria in different microhabitats of the
      rheocrenic and limnocrenic ambient springs located in urban areas showed that
      there is a high degree of cyanobacterial diversity and spatial and seasonal
      dynamics in communities. Spatial heterogeneity in relation to the type of spring
      and the type of microhabitat is reflected not only by a change in the
      quantitative structure (the number of species and their biomass), but also by a
      change in the composition of species. Seasonal changes depended on the type of
      spring and the type of microhabitat, where weather conditions influenced the
      communities by different degrees. Cyanobacterial communities of limnocrenes were
      more diverse in terms of composition and biomass, but they revealed a low
      seasonal dynamic in contrast to the communities of rheocrenes. The classification
      of springs based on their environmental conditions revealed that some springs
      were similar. The resemblance stemmed from the origin of human impact, which was
      reflected to a high degree in changes in the natural hydrochemical conditions of
      the springs. For the purpose of understanding which environmental factors had the
      greatest influence on cyanobacterial communities, a BIO-ENV procedure was
      performed. The procedure revealed that of most importance was a group of ions not
      related to the nature of the spring environment - NH4+, NO2-, NO3-, and PO43-.
      The presence of these ions in groundwater was a result of direct and indirect
      human activity in the area of aquifers. The dynamics in communities in the
      studied springs were accelerated by human impact and weather conditions.

PMID- 27876385
TI  - In old BALB/c mice, bone marrow pre-B cell and surrogate light chain reduction is
      associated with increased B cell reactivity to phosphorylcholine, but reduced T15
      idiotype dominance.
AB  - In young adult BALB/c mice, antibodies to phosphorylcholine (PC) bearing the T15
      (TEPC 15) idiotype confer protection against pneumococcal infections. In old age,
      even though PC reactive B cells are often increased, the proportion of T15+
      antibodies declines. We hypothesize that limited surrogate light chain (SLC) and
      compromise of the pre-B cell receptor checkpoint in old mice contribute to both
      reduced new B cell generation and changes in the anti-PC antibodies seen in old
      age. In old mice: 1) early pre-B cell loss is most pronounced at the preBCR
      checkpoint; however, the reduced pool of early pre-B cells continues to
      proliferate consistent with preBCR signaling; 2) increased PC reactivity is seen
      in bone marrow immature B cells; 3) deficient SLC promotes increased B cell PC
      reactivity and diminished T15 idiotype expression; and 4) as pre-B cell losses
      and reduced SLC become progressively more severe, increased T15 negative PC
      reactive B cells occur. These results associate a reduction in pre-B cells,
      imposed at the preBCR checkpoint, with increased reactivity to PC, but more
      limited expression of the protective T15 idiotype among PC reactive antibodies in
      old age.

PMID- 27876391
TI  - Critical evaluation of monitoring strategy for the multi-residue determination of
      90 chiral and achiral micropollutants in effluent wastewater.
AB  - It is essential to monitor the release of organic micropollutants from wastewater
      treatment plants (WWTPs) for developing environmental risk assessment and
      assessing compliance with legislative regulation. In this study the impact of
      sampling strategy on the quantitative determination of micropollutants in
      effluent wastewater was investigated. An extended list of 90 chiral and achiral
      micropollutants representing a broad range of biological and physico-chemical
      properties were studied simultaneously for the first time. During composite
      sample collection micropollutants can degrade resulting in the under-estimation
      of concentration. Cooling collected sub-samples to 4 degrees C stabilised >=81 of
      90 micropollutants to acceptable levels (+/-20% of the initial concentration) in
      the studied effluents. However, achieving stability for all micropollutants will
      require an integrated approach to sample collection (i.e., multi-bottle sampling
      with more than one stabilisation method applied). Full-scale monitoring of
      effluent revealed time-paced composites attained similar information to volume
      paced composites (influent wastewater requires a sampling mode responsive to flow
      variation). The option of monitoring effluent using time-paced composite samplers
      is advantageous as not all WWTPs have flow controlled samplers or suitable sites
      for deploying portable flow meters. There has been little research to date on the
      impact of monitoring strategy on the determination of chiral micropollutants at
      the enantiomeric level. Variability in wastewater flow results in a dynamic
      hydraulic retention time within the WWTP (and upstream sewerage system). Despite
      chiral micropollutants being susceptible to stereo-selective degradation, no
      diurnal variability in their enantiomeric distribution was observed. However,
      unused medication can be directly disposed into the sewer network creating short
      term (e.g., daily) changes to their enantiomeric distribution. As enantio
      specific toxicity is observed in the environment, similar resolution of enantio
      selective analysis to more routinely applied achiral methods is needed throughout
      the monitoring period for accurate risk assessment.

PMID- 27876390
TI  - Landscape changes, traditional ecological knowledge and future scenarios in the
      Alps: A holistic ecological approach.
AB  - In recent decades, a dramatic landscape change has occurred in the European
      alpine region: open areas have been naturally recolonized by forests as
      traditional agricultural and forest activities were reduced and reorganized. Land
      use changes (LUC) are generally measured through GIS and photo interpretation
      techniques, but despite many studies focused on this phenomenon and its effects
      on biodiversity and on the environment in general, there is a lack of information
      about the transformation of the human-environment connection. The study of
      Traditional Ecological Knowledge (TEK), such as the ability to recognize wild
      plants used as medicine or food, can suggest how this connection evolved through
      time and generations. This work investigates the relationship between the natural
      forest cover expansion that influences the loss of open areas and the loss of
      TEK. Different data sources and approaches were used to address the topic in all
      its complexity: a mix of questionnaire investigations, historical maps, GIS
      techniques and modelling were used to analyse past land use changes and predict
      future scenarios. The study area, Trentino, Italy, is paradigmatic of the alpine
      situation, and the land use change in the region is well documented by different
      studies, which were reviewed and compared in this paper. Our findings suggest
      that open area loss can be used as a good proxy to highlight the present state
      and to produce future scenarios of Traditional Ecological Knowledge. This could
      increase awareness of the loss of TEK in other Alpine regions, where data on TEK
      are lacking, but where environmental trends are comparable.

PMID- 27876392
TI  - Metallothionein assisted periplasmic lead sequestration as lead sulfite by
      Providencia vermicola strain SJ2A.
AB  - Lead resistant Providencia vermicola strain SJ2A was isolated from the waste of a
      battery manufacturing industry which could tolerate upto 3.0mM lead nitrate in
      the minimal medium. Interestingly, this isolate showed presence of a plasmid
      borne metallothionein gene, bmtA that matched significantly (96%) with that of
      Pseudomonas aeruginosa. Scanning electron micrographs of bacterial cells exposed
      to lead revealed a unique alteration in the cell morphology from rods to long
      inter-connected filaments. On the other hand, electron dispersive X-ray
      spectroscopy (EDX) clearly indicated no significant lead adsorption therefore, we
      speculated intracellular sequestration in this bacterial strain. Transmission
      electron micrographs of the bacterial cells exposed to lead evidently
      demonstrated periplasmic sequestration of lead which was also supported by
      Fourier transformed infrared spectroscopic (FTIR) analysis. The bacterium
      internalised 155.12mg Pb2+/g biomass as determined by atomic absorption
      spectroscopy. Subsequently, the accumulated lead was identified as lead sulfite
      by X-ray diffraction studies. Therefore P. vermicola strain SJ2A has potential to
      bioremediate lead contaminated environmental sites.

PMID- 27876393
TI  - Bilateral vallecular cysts.

PMID- 27876394
TI  - Postnatal irradiation-induced hippocampal neuropathology, cognitive impairment
      and aging.
AB  - Irradiation of the brain in early human life may set abnormal developmental
      events into motion that last a lifetime, leading to a poor quality of life for
      affected individuals. While the effect of irradiation at different early
      developmental stages on the late human life has not been investigated
      systematically, animal experimental studies suggest that acute postnatal
      irradiation with ?0.1Gy may significantly reduce neurogenesis in the dentate
      gyrus and endotheliogenesis in cerebral vessels and induce cognitive impairment
      and aging. Fractionated irradiation also reduces neurogenesis. Furthermore,
      irradiation induces hippocampal neuronal loss in CA1 and CA3 areas,
      neuroinflammation and reduces gliogenesis. The hippocampal neurovascular niche
      and the total number of microvessels are also changed after radiation exposures.
      Each or combination of these pathological changes may cause cognitive impairment
      and aging. Interestingly, acute irradiation of aged brain with a certain amount
      of radiation has also been reported to induce brain hormesis or neurogenesis. At
      molecular levels, inflammatory cytokines, chemokines, neural growth factors,
      neurotransmitters, their receptors and signal transduction systems, reactive
      oxygen species are involved in radiation-induced adverse effect on brain
      development and functions. Further study at different omics levels after low
      dose/dose rate irradiation may not only unravel the mechanisms of radiation
      induced adverse brain effect or hormesis, but also provide clues for detection or
      diagnosis of radiation exposure and for therapeutic approaches to effectively
      prevent radiation-induced cognitive impairment and aging. Investigation focusing
      on radiation-induced changes of critical brain development events may reveal many
      previously unknown adverse effects.

PMID- 27876395
TI  - Massive lamotrigine poisoning. A case report.
AB  - Lamotrigine (LTG) represents the most commonly prescribed of the so-called new
      generation antiepileptic drugs. We describe a child who was admitted to the
      emergency room because of generalized tonic-clonic status epilepticus followed by
      a complex neurological picture with hyperkinesia and acute ataxia as a result of
      a LTG intoxication. The experience on acute LTG intoxication is very limited in
      pediatrics. The present case provides information on the clinical picture related
      to LTG overdose and confirms that drug intoxications should be considered in the
      differential diagnosis strategy when severe and polymorphic neurological symptoms
      occur acutely.

PMID- 27876396
TI  - Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal
      microcephaly.
AB  - Several recent articles published by Brain and Development in 2016 demonstrated
      some rare, but innovative, genetic mechanisms for microcephaly. This concise mini
      review presented another novel pathogenic mechanism for microcephaly, which has
      actually been a worldwide medical challenge since the World Health Organization
      (WHO) defined the outbreak of the Zika virus (ZIKV) as an International Public
      Health Emergency on 1 Feb, 2016. As a recent noteworthy clinical phenomenon, the
      ZIKV outbreak was accompanied by a dramatically increased number of microcephalus
      fetuses. However, no direct evidence supporting the suspected pathogenic effects
      of ZIKV on fetal microcephaly was shown previously before 2016. Herein, we
      evaluated the most important human pathological, animal developmental, and neuro
      cytotoxic findings released in 2016, and highlighted the original experimental
      evidence that strengthens the potential link between ZIKV and the high incidence
      of microcephaly in new-born babies. Because killing mosquitoes via insecticides
      is currently the only effective way to suppress ZIKV-induced disorders, the
      animal and cellular models described in this mini-review are very beneficial to
      anti-ZIKV drug development and vaccine assessment.

PMID- 27876397
TI  - Efficacy of sodium channel blockers in SCN2A early infantile epileptic
      encephalopathy.
AB  - BACKGROUND: Recent clinical evidence supports a targeted therapeutic approach for
      genetic epileptic encephalopathies based on the molecular dysfunction. PATIENT
      DESCRIPTION: A 2-day-old male infant presented with epileptic encephalopathy
      characterized by burst-suppression EEG background and tonic-clonic migrating
      partial seizures. The condition was refractory to phenobarbital, pyridoxine,
      pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous
      loading dose of phenytoin was documented by video-EEG monitoring. Over weeks
      phenytoin was successfully switched to carbamazepine to prevent seizure relapses
      associated with difficulty in maintaining proper blood levels of phenytoin.
      Genetic analysis identified a novel de novo heterozygous mutation
      (c.[4633A>G]p.[Met1545Val]) in SCN2A. At two years and three months of age the
      patient is still seizure-free on carbamazepine, although a developmental delay is
      evident. CONCLUSIONS: Sodium channel blockers represent the first-line treatment
      for confirmed or suspected SCN2A-related epileptic encephalopathies. In severe
      cases with compatible electro-clinical features we propose a treatment algorithm
      based on a test trial with high dose intravenous phenytoin followed in case of a
      positive response by carbamazepine, more suitable for long-term maintenance
      treatment. Because of their rarity, collaborative studies are needed to delineate
      shared therapeutic protocols for EIEE based on the electro-clinical features and
      the presumed underlying genetic substrate.

PMID- 27876398
TI  - Dropped head congenital muscular dystrophy caused by de novo mutations in LMNA.
AB  - BACKGROUND: Dropped head syndrome is an easily recognizable clinical presentation
      of Lamin A/C-related congenital muscular dystrophy. Patients usually present in
      the first year of life with profound neck muscle weakness, dropped head, and
      elevated serum creatine kinase. CASE DESCRIPTION: Two patients exhibited head
      drop during infancy although they were able to sit independently. Later they
      developed progressive axial and limb-girdle weakness. Creatine kinase levels were
      elevated and muscle biopsies of both patients showed severe dystrophic changes.
      The distinctive clinical hallmark of the dropped head led us to the diagnosis of
      Lamin A/C-related congenital muscular dystrophy, with a pathogenic de novo
      mutation p.Glu31del in the head domain of the Lamin A/C gene in both patients.
      Remarkably, one patient also had a central involvement with white matter changes
      on brain magnetic resonance imaging. CONCLUSION: Lamin A/C-related dropped-head
      syndrome is a rapidly progressive congenital muscular dystrophy and may lead to
      loss of ambulation, respiratory insufficiency, and cardiac complications. Thus,
      the genetic diagnosis of dropped-head syndrome as L-CMD and the implicated
      clinical care protocols are of vital importance for these patients. This disease
      may be underdiagnosed, as only a few genetically confirmed cases have been
      reported.

PMID- 27876399
TI  - National survey of practice of faecal microbiota transplantation for Clostridium
      difficile infection in the UK.

PMID- 27876400
TI  - A dynamic regression analysis tool for quantitative assessment of bacterial
      growth written in Python.
AB  - Herein, an open-source method to generate quantitative bacterial growth data from
      high-throughput microplate assays is described. The bacterial lag time, maximum
      specific growth rate, doubling time and delta OD are reported. Our method was
      validated by carbohydrate utilization of lactobacilli, and visual inspection
      revealed 94% of regressions were deemed excellent.

PMID- 27876402
TI  - Corrigendum to "Characterization of the cell growth analysis for detection of
      immortal cellular impurities in human mesenchymal stem cells" [Biologicals 43 (2)
      (March 2015) 146-149].

PMID- 27876401
TI  - Developmental coordination disorder and its cause: The road less travelled.
AB  - We critically review the research literature that seeks to focus on the possible
      cause of children diagnosed with developmental coordination disorder (DCD). In so
      doing we contrast the traditional information processing (IP) approach as a model
      to explain the causal factors that account for the motor deficits present in
      children with DCD, with a dynamical systems (DS) account which argues that
      coordination deficits in children with DCD is less to do with problems of poor
      internal models (a cornerstone of IP theory) and more with a degrading of
      perception-action coupling. We review and comment on the extant empirical data
      and conclusions of both approaches. We conclude that the data for an IP
      explanation is weak and a reconsideration of DCD is in order with respect to the
      underlying cause of this issue.

PMID- 27876404
TI  - Very early discharge compared with early or non-early discharge in children with
      cancer and febrile neutropenia: A Cochrane review summary.

PMID- 27876403
TI  - Characterizing the high-risk homebound patients in need of nurse practitioner co
      management.
AB  - By providing more frequent provider visits, prompt responses to acute issues, and
      care coordination, nurse practitioner (NP) co-management has been beneficial for
      the care of chronically ill older adults. This paper describes the homebound
      patients with high symptom burden and healthcare utilization who were referred to
      an NP co-management intervention and outlines key features of the intervention.
      We compared demographic, clinical, and healthcare utilization data of patients
      referred for NP co-management within a large home-based primary care (HBPC)
      program (n = 87) to patients in the HBPC program not referred for co-management
      (n = 1027). A physician survey found recurrent hospitalizations to be the top
      reason for co-management referral and a focus group with nurses and social
      workers noted that co-management patients are typically those with active medical
      issues more so than psychosocial needs. Co-management patients are younger than
      non-co-management patients (72.31 vs. 80.30 years old, P < 0.001), with a higher
      mean Charlson comorbidity score (3.53 vs. 2.47, P = 0.0001). They have higher
      baseline annual hospitalization rates (2.27 vs. 0.61, P = 0.0005) and total
      annual home visit rates (13.1 vs. 6.60, P = 0.0001). NP co-management can be
      utilized in HBPC to provide intensive medical management to high-risk homebound
      patients.

PMID- 27876405
TI  - Lower urinary tract symptoms in children and adolescents with Williams-Beuren
      syndrome.
AB  - INTRODUCTION: Williams-Beuren syndrome (WBS) is a genetic condition caused by a
      microscopic deletion in the chromosome band 7q11.23. Individuals with WBS may
      present with congenital cardiovascular defects, neurodevelopmental disturbances
      and structural abnormalities of the urinary tract. Lower urinary tract symptoms
      (LUTS) seem to be frequent in this population, but studies on this topic are
      scarce and based on small case series. OBJECTIVE: To systematically evaluate the
      prevalence of lower urinary tract symptoms (LUTS) and the acquisition of bladder
      control in a large population with WBS. STUDY DESIGN: A cross-sectional study
      evaluating 87 consecutive patients with WBS; there were 41 girls and 46 boys.
      Genetic studies confirmed WBS in all patients. Subjects were clinically evaluated
      with: a history of LUTS obtained from the parents and child, a structured
      questionnaire of LUTS, a 3-day urinary frequency-volume chart, a quality of life
      question regarding LUTS, and physical examination. A history regarding the
      acquisition of bladder control was directly evaluated from the parents. RESULTS:
      Mean age of patients was 9.0 +/- 4.2 years, ranging from 3 to 19 years. Based on
      the symptoms questionnaire and the frequency-volume chart, 70 patients (80.5%)
      were symptomatic. The most common symptom was urgency, affecting 61 (70.1%)
      patients, followed by increased urinary frequency in 60 (68.9%) patients, and
      urge-incontinence in 53 (60.9%), as shown in Summary Fig. More than half of the
      children reported nocturnal enuresis, including 61% of the girls and 52% of the
      boys. Twenty-three patients (25.6%) had a history of urinary tract infections.
      The mean age for acquisition of dryness during the day was 4.4 +/- 1.9 years.
      Parents of 61 patients (70.1%) acknowledged that LUTS had a significant impact on
      the quality of life of their children. DISCUSSION: A high prevalence of LUTS was
      confirmed with a significant negative impact on quality of life in a large
      population of children and adolescents with WBS. It was shown for the first time
      that the achievement of daytime bladder control is delayed in children with WBS.
      Although LUTS are not recognized as one of the leading features of the syndrome,
      it is believed that it should be considered as a significant characteristic of
      the clinical diagnosis of WBS. CONCLUSIONS: LUTS are highly prevalent in children
      and adolescents with WBS and have a significant negative impact on patient's
      quality of life.

PMID- 27876406
TI  - Adenotonsillectomy can decrease enuresis and sympathetic nervous activity in
      children with obstructive sleep apnea syndrome.
AB  - BACKGROUND: The nocturnal intermittent hypoxia caused by obstructive sleep apnea
      syndrome (OSAS) can provoke the sympathetic nervous activity (SNA). Salivary
      alpha-amylase (sAA) is a sensitive, non-invasive biomarker for reflecting the
      SNA, and a useful marker for pediatric OSAS subjects. Adenotonsillar hypertrophy
      (ATH) is the most commonly identified risk factor in OSAS childhood, therefore,
      several studies showed that the adenotonsillectomy (T&A) may alleviate nocturnal
      enuresis (NE) in children with OSAS. OBJECTIVE: The present study was to
      investigate the effect of T&A on NE, the change of sAA value in ATH and OSAS
      children, with/without NE, and with/without the operation. STUDY DESIGN: 37
      children (Group A) were admitted for ATH and NE. The saliva samples were taken
      before and after polysomnography for the measure of sAA. After the T&A, the
      children were followed-up for 1 year. 35 OSAS children with NE but no T&A were as
      a NE watchful-waiting group (Group B), 32 subjects without OSAS or NE were as non
      OSAS control (Group C), 42 cases who underwent T&A but did not have NE were
      admitted to evaluate the SNA (Group D). Follow-up included evaluations for NE,
      sAA and urinary catecholamine after the T&A or at the equivalent time points.
      RESULTS: The observational results in the present study showed a significant rate
      of the disappearance of NE 1 month after the T&A and had an almost complete
      resolution 1 year later. OSAS may irritate oxidative stress and increase SNA in
      pediatric subjects, which reflected by increased levels of sAA and urinary
      catecholamine, while the T&A can decrease enuresis and the SNA in children with
      OSAS (Figure). DISCUSSION: Little research has previously focused on the
      relationship between childhood OSAS and the SNA. No data are currently available
      regarding comparisons of sAA levels before and after the T&A in children with
      OSAS and enuresis. Our findings in this present study showed that there was a
      resolution or decrease in enuresis events and drops in sAA levels following T&A,
      which were consistent with earlier study. However, there was no significant
      difference in the urinary catecholamine levels was found between OSAS groups with
      or without NE. Furthermore, there was no correlation between the urinary
      catecholamine and polysomnography parameters. CONCLUSIONS: T&A has a favorable
      therapeutic effect on NE and may decrease SNA in children with OSAS. sAA might be
      associated with instability of ANS by OSAS and have a consistent relationship
      with the apnea-hypopnea index. Our studying aims had been met.

PMID- 27876407
TI  - Complement C3 Exacerbates Imiquimod-Induced Skin Inflammation and Psoriasiform
      Dermatitis.

PMID- 27876408
TI  - Brain stimulation as a neuromodulatory epilepsy therapy.
AB  - Brain stimulation is increasingly used in epilepsy patients with insufficient
      therapeutic response to pharmacological treatment. Whereas vagus nerve
      stimulation with implanted devices has been used in large and heterogeneous
      patient groups, new devices also enable targeted brain stimulation at the site of
      seizure generation (responsive neurostimulation) or at network hubs (thalamic
      stimulation). Both responsive neurostimulation systems targeting the epileptic
      focus and the latest vagus nerve stimulators are intended to stimulate during the
      ictal phase to disrupt clinical seizure manifestation of reduce seizure severity.
      Furthermore, transcutaneous stimulation approaches are now available, although
      their efficacy remains uncertain. This review explains the concepts underlying
      brain stimulation, provides an overview of efficacy and tolerability data and
      discusses the rational use of the growing spectrum of neuromodulatory strategies
      available.

PMID- 27876409
TI  - Knowledge and practice of intensive care nurses for endotracheal suctioning in a
      teaching hospital in western Turkey.
AB  - OBJECTIVES: This study was conducted to determine intensive care nurses'
      knowledge and practice levels regarding open system endotracheal suctioning and
      to investigate if there is a relationship between nurses' demographic
      characteristics and their knowledge and practice. RESEARCH METHODOLOGY/DESIGN:
      The study was conducted as a cross-sectional and non-participant structured
      observational design. Data were collected using a 45-item structured and self
      administered questionnaire and a 31-item observational checklist. The study
      sample included 72 nurses. SETTING: Three adult intensive care units in a
      teaching hospital. RESULTS: The nurses' mean scores of knowledge and practice
      were 23.79+/-3.83 and 12.88+/-2.53. Their level of knowledge was very good in
      59.7%, good in 34.7%, and the level of practice was fair in 79.2% and good in
      18.1%. The relationship between the type of unit and the nurses' knowledge scores
      was statistically significant (p=0.013). The correlation between the nurses'
      scores of knowledge and practice was not statistically significant (r=0.220;
      p=0.063). CONCLUSION: This study suggests that the knowledge level of most of the
      nurses was good and their practice level was fair. Intensive care nurses must
      perform suctioning procedures safely and effectively to ensure delivery of
      quality of care and eliminate complications.

PMID- 27876410
TI  - Clinical outcome of high-dose-rate interstitial brachytherapy in vulvar cancer: A
      single institutional experience.
AB  - PURPOSE: With an aim to evaluate and report high dose date interstitial
      brachytherapy (HDR-ISBT) in vulvar cancers, we undertook this retrospective
      analysis. METHODS AND MATERIALS: Histologically proven vulvar cancers treated
      with HDR-ISBT between 2001 and 2016 were analyzed. Radiotherapy details, clinical
      outcome in terms of local control rates, survivals, and toxicities were
      evaluated. RESULTS: A total of 38 patients received HDR-ISBT, with definitive
      radiation in 29 (76.3%), adjuvant postoperative in six (15.8%) and salvage
      radiation in three (7.9%) patients. Of them, 29 patients received brachytherapy
      boost and nine patients ISBT alone. BT procedure included freehand plastic tube
      technique in 23 (single [n = 5] or multiple plane [n = 18]), 13 patients with
      template based and two patients combined approach. Patients with brachytherapy
      alone received median EQD2 of 38.4 Gy10 (35.5-46.7 Gy10), as boost received
      median 23.3 Gy10 (13-37.3 Gy10). At 3-month post-treatment response evaluation,
      30 patients achieved clinically complete response, two patients partial response
      and six maintained postoperative status. With a median follow-up of 30 months, 29
      (76.3%) were disease free, and 9 (23.7%) patients had relapsed disease with four
      patients expired due to disease and two died of other causes. The 5-year overall
      survival, disease free survival, and local control rates were 82%, 51%, and 77%,
      respectively. CONCLUSIONS: HDR-ISBT in vulvar cancer is a feasible and a viable
      option with acceptable and comparable outcomes.

PMID- 27876413
TI  - Association between plasma Torque teno virus level and chronic lung allograft
      dysfunction after lung transplantation.

PMID- 27876412
TI  - Advanced symptoms are associated with myocardial damage in patients with severe
      aortic stenosis.
AB  - BACKGROUND: Once aortic stenosis (AS) is severe, patients develop symptoms at
      different stages. Indeed, symptom status may correlate poorly with the grade of
      valve narrowing. Multiple pathophysiological mechanisms, other than valvular
      load, may explain the link between AS and symptom severity. We aimed to describe
      the relationship between the severity of symptoms and the characteristics of a
      cohort of patients with severe AS already referred for aortic valve replacement
      (AVR). METHODS: We analyzed 118 consecutive patients (70+/-9 years, 55% men) with
      severe AS referred for AVR. We identified 84 patients with New York Heart
      Association (NYHA) I-II, and 34 with NYHA III-IV symptoms. Clinical and
      echocardiographic parameters were compared between these two groups. Left
      ventricular ejection fraction (LVEF), global longitudinal peak systolic strain
      (GLPS), NT-pro-B-type natriuretic peptide (BNP), and high-sensitive troponin T
      (hs-TNT) were determined at the time of admission. RESULTS: AS severity was
      similar between groups. Compared with the NYHA I-II group, patients in NYHA III
      IV group were older and more likely to have comorbidities, worse intracardiac
      hemodynamics and more LV damage. Variables independently associated with NYHA III
      IV symptomatology were the absence of sinus rhythm, higher E/e' ratio, and
      increased hs-TNT. GLPS showed a good correlation not only with hs-TNT as a marker
      of myocardial damage, but also with markers of increased afterload imposed on LV,
      being not directly related with advanced symptoms. CONCLUSIONS: Advanced symptoms
      in patients with severe AS referred for AVR are associated with worse
      intracardiac hemodynamics, absence of sinus rhythm, and more myocardial damage.
      It supports the concept of transition from adaptive LV remodeling to myocyte
      death as an important determinant of symptoms of heart failure.

PMID- 27876414
TI  - Looking on the BRIGHT side of health literacy in patients with cardiac
      transplantation: Where are we and where do we need to go?

PMID- 27876415
TI  - The relationship between historical development and potentially toxic element
      concentrations in urban soils.
AB  - Increasing urbanisation has a direct impact on soil quality, resulting in
      elevated concentrations of potentially toxic elements (PTEs) in soils. This
      research aims to assess if soil PTE concentrations can be used as an
      'urbanisation tracer' by investigating geogenic and anthropogenic source
      contributions and controls, and considering PTE enrichment across historical
      urban development zones. The UK cities of Belfast and Sheffield are chosen as
      study areas, where available shallow and deep concentrations of PTEs in soil are
      compared to identify geogenic and anthropogenic contributions to PTEs. Cluster
      analysis and principal component analysis are used to elucidate the main controls
      over PTE concentrations. Pollution indices indicate that different periods of
      historical development are linked to enrichment of different PTEs. Urban
      subdomains are identified and background values calculated using various
      methodologies and compared to generic site assessment criteria. Exceedances for a
      number of the PTEs considered suggest a potential human health risk could be
      posed across subdomains of both Belfast and Sheffield. This research suggests
      that airborne diffuse contamination from often historical sources such as
      traffic, domestic combustion and industrial processes contribute greatly to soil
      contamination within urban environments. The relationship between historical
      development and differing PTEs is a novel finding, suggesting that PTEs have the
      potential for use as 'urbanisation tracers'. The investigative methodology
      employed has potential applications for decision makers, urban planners,
      regulators and developers of urban areas.

PMID- 27876411
TI  - Disruption of mitochondrial quality control in peripheral artery disease: New
      therapeutic opportunities.
AB  - Peripheral artery disease (PAD) is a multifactorial disease initially triggered
      by reduced blood supply to the lower extremities due to atherosclerotic
      obstructions. It is considered a major public health problem worldwide, affecting
      over 200 million people. Management of PAD includes smoking cessation, exercise,
      statin therapy, antiplatelet therapy, antihypertensive therapy and surgical
      intervention. Although these pharmacological and non-pharmacological
      interventions usually increases blood flow to the ischemic limb, morbidity and
      mortality associated with PAD continue to increase. This scenario raises new
      fundamental questions regarding the contribution of intrinsic metabolic changes
      in the distal affected skeletal muscle to the progression of PAD. Recent evidence
      suggests that disruption of skeletal muscle mitochondrial quality control
      triggered by intermittent ischemia-reperfusion injury is associated with
      increased morbidity in individuals with PAD. The mitochondrial quality control
      machinery relies on surveillance systems that help maintaining mitochondrial
      homeostasis upon stress. In this review, we describe some of the most critical
      mechanisms responsible for the impaired skeletal muscle mitochondrial quality
      control in PAD. We also discuss recent findings on the central role of
      mitochondrial bioenergetics and quality control mechanisms including
      mitochondrial fusion-fission balance, turnover, oxidative stress and aldehyde
      metabolism in the pathophysiology of PAD, and highlight their potential as
      therapeutic targets.

PMID- 27876416
TI  - Influence of bacterial extracellular polymeric substances on the sorption of Zn
      on gamma-alumina: A combination of FTIR and EXAFS studies.
AB  - Extracellular polymeric substances (EPS) isolated from bacteria, are abound of
      functional groups which can react with metals and consequently influence the
      immobilization of metals. In this study, we combined with Zn K-edge Extended X
      ray Absorption Fine Structure (EXAFS), Fourier Transform Infrared (FTIR)
      spectroscopy, and High-Resolution Transmission Electron Microscopy (HRTEM)
      techniques to study the effects of EPS isolated from Bacillus subtilis and
      Pseudomonas putida on Zn sorption on gamma-alumina. The results revealed that Zn
      sorption on aluminum oxide was pH-dependent and significantly influenced by
      bacterial EPS. At pH 7.5, Zn sorbed on gamma-alumina was in the form of Zn-Al
      layered doubled hydroxide (LDH) precipitates, whereas at pH 5.5, Zn sorbed on
      gamma-alumina was as a Zn-Al bidentate mononuclear surface complex. The amount of
      sorbed Zn at pH 7.5 was 1.3-3.7 times higher than that at pH 5.5. However, in the
      presence of 2 g L-1 EPS, regardless of pH conditions and EPS source, Zn + EPS +
      gamma-alumina ternary complex was formed on the surface of gamma-alumina, which
      resulted in decreased Zn sorption (reduced by 8.4-67.8%) at pH 7.5 and enhanced
      Zn sorption (increased by 10.0-124.7%) at pH 5.5. The FTIR and EXAFS spectra
      demonstrated that both the carboxyl and phosphoryl moieties of EPS were crucial
      in this process. These findings highlight EPS effects on Zn interacts with gamma
      alumina.

PMID- 27876417
TI  - Does long term low impact stress cause population extinction?
AB  - This study assessed and monitored 40 consecutive reproduction tests -
      multigenerational (MG) - of continuous exposure to Cd (at 2 reproduction Effect
      Concentrations (EC): EC10 and EC50) using the standard soil invertebrate Folsomia
      candida, in total 3.5 years of data were collected. Endpoints included survival,
      reproduction, size and metallothionein (MTc) gene expression. Further, to
      investigate adaptation to the toxicant, additional standard toxicity experiments
      were performed with the MG organisms of F6, F10, F26, F34 and F40 generations of
      exposure. Exposure to Cd EC10 caused population extinction after one year,
      whereas populations survived exposure to Cd EC50. Cd induced the up-regulation of
      the MTc gene, this being higher for the higher Cd concentration, which may have
      promoted the increased tolerance at the EC50. Moreover, EC10 induced a shift
      towards organisms of smaller size (positive skew), whereas EC50 induced a shift
      towards larger size (negative skew). Size distribution shifts could be an effect
      predictor. Sensitivity increased up to F10, but this was reverted to values
      similar to F0 in the next generations. The maximum Cd tolerance limits of F.
      candida increased for Cd EC50 MG. The consequences for risk assessment are
      discussed.

PMID- 27876418
TI  - Polycyclic aromatic hydrocarbons (PAHs) enriching antibiotic resistance genes
      (ARGs) in the soils.
AB  - The prevalence of antibiotic resistance genes (ARGs) in modern environment raises
      an emerging global health concern. In this study, soil samples were collected
      from three sites in petrochemical plant that represented different pollution
      levels of polycyclic aromatic hydrocarbons (PAHs). Metagenomic profiling of these
      soils demonstrated that ARGs in the PAHs-contaminated soils were approximately 15
      times more abundant than those in the less-contaminated ones, with
      Proteobacterial being the preponderant phylum. Resistance profile of ARGs in the
      PAHs-polluted soils was characterized by the dominance of efflux pump-encoding
      ARGs associated with aromatic antibiotics (e.g., fluoroquinolones and
      acriflavine) that accounted for more than 70% of the total ARGs, which was
      significantly different from representative sources of ARG pollution due to wide
      use of antibiotics. Most of ARGs enriched in the PAHs-contaminated soils were not
      carried by plasmids, indicating the low possibilities of them being transferred
      between bacteria. Significant correlation was observed between the total
      abundance of ARGs and that of Proteobacteria in the soils. Proteobacteria
      selected by PAHs led to simultaneously enriching of ARGs carried by them in the
      soils. Our results suggested that PAHs could serve as one of selective stresses
      for greatly enriching of ARGs in the human-impacted environment.

PMID- 27876420
TI  - Hereditary bilateral genu recurvatum: Case report of a family.
AB  - BACKGROUND: Genu recurvatum is a rare condition in children and adolescents. The
      origin can be osseous, ligamentous and mixed. METHODS: We describe for the first
      time a family inclusive two brothers and their mother with hereditary bilateral
      genu recurvatum of unknown etiology. The possible underlying pathology and
      treatment are discussed. RESULTS: The underlying pathology of the early closure
      of the apophysis of the tibial tuberosity remained unclear. The mother was never
      treated, one of the brothers received a tibial osteotomy as a young adult. Both
      patients developed end-stage osteoarthritis of both knees which was successfully
      treated by a bilateral computer-navigated TKA. At seven to eight years after
      implantation in the older brother (left and right knee, respectively) and three
      to four years after implantation in the younger brother (right and left knee,
      respectively), the Visual Analogue Scale (VAS) pain score on a 0 to 100 scale was
      0 of both brothers, the EQ-5D health status was 80 (scale of 0 to 100), the
      satisfaction was 10 (scale of 10) of both brothers. The Knee Injury and
      Osteoarthritis Outcome Score (KOOS) function of the younger brother of 75 (scale
      0 to 100) and of the older brother 100. The KOOS sport of the younger brother was
      10 (scale 0 to 100), whereas that of the older brother 85. CONCLUSIONS:
      Hereditary bilateral genu recurvatum with end-stage osteoarthritis can be
      successfully treated with computer-navigated TKAs; however, impingement of the
      patella on the proximal tibia and the position of the tibial keel are of concern.

PMID- 27876419
TI  - Assessing the potential of inorganic anions (Cl-, NO3-, SO42- and PO43-) to
      increase the bioaccessibility of emitted palladium in the environment:
      Experimental studies with soils and a Pd model substance.
AB  - Palladium (Pd) emitted from vehicles equipped with exhaust catalytic converters
      has been accumulating at a greater rate relative to other platinum group elements
      (PGE) in the last 10-20 years. Little is known, however, regarding the various
      environmental factors and conditions which are likely to modulate the chemical
      behavior and bioaccessibility of this element post-emission. To meet data needs,
      soils and a Pd model substance were treated with solutions containing common
      anions (Cl-, NO3-, SO42- und PO43-) to shed light on the geochemical behavior of
      emitted Pd under ambient conditions. As part of this, the particle surface
      chemistry of treated residues (insoluble phase) and solutions (soluble phase) was
      examined using XPS to assess the chemical transformation of Pd in the presence of
      inorganic anions. The results show that Pd is the most soluble in the presence of
      anionic species, followed by rhodium (Rh) and platinum (Pt). Pd in field
      collected samples was found to be considerably more soluble than the metallic Pd
      in the model substance, Pd black, when treated with anionic species. The results
      also demonstrate that the solubility of Pd black is strongly dependent on
      solution pH, concentration and the duration of reaction. The outer 3-4 atomic
      layers of metallic Pd was determined via XPS to be partially oxidized when
      treated with anion solutions, with the degree being dependent on anion type. The
      concentration of dissolved O2 in solution was found to have little impact on the
      transformation of metallic Pd. Given the ubiquitous nature of the anions
      examined, we can expect that Pd will become more bioaccessible post-emission.

PMID- 27876421
TI  - Prognostic factors for patients undergoing vitrified-warmed human embryo transfer
      cycles: a retrospective cohort study.
AB  - We examined the prognostic factors for pregnancy in 210 vitrified-warmed embryo
      transfer (ET) cycles in 121 patients. The univariate analysis showed that age,
      gravida, the number of cycles associated with infertility caused by
      endometriosis, the number of previous assisted reproductive technology (ART)
      treatment cycles, and the number of ICSI procedures were significantly lower in
      pregnant cycles compared with non-pregnant cycles. The percentages of ET using at
      least one intact embryo and of ET using at least one embryo that had developed
      further after warming were significantly higher in pregnant cycles compared with
      non-pregnant cycles. Multivariate logistic regression analysis showed that
      previous ART treatment cycles, ET with at least one intact embryo, and ET using
      at least one embryo that had developed further were independent prognostic
      factors for pregnancy in vitrified-warmed ET cycles. We conclude that fewer
      previous ART treatment cycles, ET using at least one intact embryo, and ET with
      embryos that have developed further after warming might be favourable prognostic
      factors for pregnancy in vitrified-warmed ET cycles.

PMID- 27876422
TI  - Validation of the Internet Gaming Disorder Scale - Short-Form (IGDS9-SF) in an
      Italian-speaking sample.
AB  - Background and aims The inclusion of Internet Gaming Disorder (IGD) in Section
      III of the fifth edition of the Diagnostic and Statistical Manual of Mental
      Disorders has increased the interest of researchers in the development of new
      standardized psychometric tools for the assessment of such a disorder. To date,
      the nine-item Internet Gaming Disorder Scale - Short-Form (IGDS9-SF) has only
      been validated in English, Portuguese, and Slovenian languages. Therefore, the
      aim of this investigation was to examine the psychometric properties of the IGDS9
      SF in an Italian-speaking sample. Methods A total of 757 participants were
      recruited to the present study. Confirmatory factor analysis and multi-group
      analyses were applied to assess the construct validity. Reliability analyses
      comprised the average variance extracted, the standard error of measurement, and
      the factor determinacy coefficient. Convergent and criterion validities were
      established through the associations with other related constructs. The receiver
      operating characteristic curve analysis was used to determine an empirical cut
      off point. Results Findings confirmed the single-factor structure of the
      instrument, its measurement invariance at the configural level, and the
      convergent and criterion validities. Satisfactory levels of reliability and a cut
      off point of 21 were obtained. Discussion and conclusions The present study
      provides validity evidence for the use of the Italian version of the IGDS9-SF and
      may foster research into gaming addiction in the Italian context.

PMID- 27876423
TI  - Environmental indicators for human norovirus outbreaks.
AB  - Norovirus is the most common cause of outbreaks of non-bacterial gastroenteritis
      in human. While the winter seasonality of norovirus outbreaks has been widely
      reported, the association between norovirus outbreak epidemics and environmental
      factors remains not fully understood. This literature review is intended to
      improve understanding of environmental factors governing norovirus outbreaks and
      how the factors affect norovirus transmission. To that end, a large number of
      studies (67) from countries around the world were critically reviewed and
      discussed. Results of the literature review show that temperature, humidity, and
      rainfall are the most important environmental variables governing the norovirus
      epidemic cycle. It was found that low temperature between -6.6 and 20  degrees C,
      relative humidity between 10 and 66 %, and rainfall from 1 day to 3 months before
      an outbreak are effective ranges of the environmental factors, which favor the
      prevalence of norovirus. Some other environmental factors might have an
      association with the cycle of norovirus epidemics. However, further
      investigations are needed to understand effects of the other factors on norovirus
      incidence. The findings of this literature review improve our understanding of
      the relationship between norovirus outbreaks and environmental factors and
      provide the direction for future research on norovirus outbreaks.

PMID- 27876424
TI  - Surface and volume non-invasive methods for the structural monitoring of the bass
      relief 'Madonna con Bambino' (Gorizia, Northern Italy).
AB  - Structural analysis of marble statues, carried out by non-invasive and in situ
      methods, is crucial to define the state of conservation of the artworks and to
      identify the deterioration phenomena that can affect them. In this work, we
      combined in situ non-destructive techniques, ultrasonic tomography (US),
      ultraviolet-induced visible fluorescence (UV-IF) and X-ray fluorescence (XRF) to
      study the bass-relief 'Madonna con Bambino' (Gorizia, Italy). The US revealed the
      presence of some metallic pivots, associated with areas of high sound velocity;
      moreover, a more degraded area has been identified in the lower part of the bass
      relief. The acquired UV-IF image confirmed the presence of surface degradation,
      allowing a preliminary evaluation of the extension of a fracture, from surface to
      bulk. In addition, the different materials (both original and/or integrations)
      that compose the studied surface have been identified. The XRF has contributed to
      define the nature of the inorganic materials applied during undocumented previous
      restoration works on the surface as filler for lacunae.

PMID- 27876425
TI  - How can lipid nanocarriers improve transdermal delivery of olanzapine?
AB  - The development of a transdermal nanocarrier drug delivery system with potential
      for the treatment of psychiatric disorders, such as schizophrenia and bipolar
      disorder, is described. Lipid nanocarriers (LN), encompassing various
      solid:liquid lipid compositions were formulated and assessed as potential
      nanosystems for transdermal delivery of olanzapine. A previously optimized method
      of hot high pressure homogenization (HPH) was adopted for the production of the
      LN, which comprised solid lipid nanoparticles (SLN), nanostructured lipid
      carriers (NLC) and nanoemulsions (NE). Precirol (r) was selected as the solid
      lipid for progression of studies. SLN exhibited the best performance for
      transdermal delivery of olanzapine, based on in vitro release and permeation
      studies, coupled with results from physicochemical characterization of several
      solid:liquid lipid formulations. Stability tests, performed to give an indication
      of long-term storage behavior of the formulations, were in good agreement with
      previous studies for the best choice of solid:liquid lipid ratio. Overall, these
      findings highlight the SLN-based formulation as promising for the further
      inclusion in and production of transdermal patches, representing an innovative
      therapeutic approach.

PMID- 27876426
TI  - Pin1 and secondary hyperparathyroidism of chronic kidney disease: gene
      polymorphisms and protein levels.
AB  - BACKGROUND: Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a
      key regulator of PTH mRNA stability. Secondary hyperparathyroidism (SHPT), which
      is characterized by elevated serum PTH levels, is a common complication of CKD.
      We investigated the possible associations between CKD with SHPT (CKD SHPT) and
      single-nucleotide polymorphisms of the Pin1 gene and compared the levels of the
      Pin1 protein in the CKD SHPT patients with those of the controls. METHODS: The
      study group included 251 CKD SHPT patients and 61 controls. One putative
      functional SNP (single nucleotide polymorphism) in the Pin1 promoter (rs2233679C
      > T: c.-667C > T) is the main object. Genotyping was performed on purified DNA
      using polymerase chain reaction-restriction (PCR) and restriction fragment length
      polymorphisms (RFLP). The levels of Pin1 were measured in serum using an enzyme
      linked immunosorbent assay. RESULTS: Genotyping showed that CT + TT in the Pin1
      promoter was significantly more common in the CKD SHPT group than in the control
      group (p<.05). The correlation analysis demonstrated that a significant
      difference in the C to T transition in the Pin1 promoter contributed to CKD SHPT
      (chi2=12.47, p<.05; Odds ratios (OR) = 1.26, 95% confidence (CI) intervals =1.06
      1.49). The multivariate logistic regression analysis reported that the OR and
      95%CI were 12.693 and 2.029-75.819 (p<.05), respectively, in the Pin1 gene
      promoter -667T variant genotypes (CT + TT) after adjusting for other factors, and
      those values in Pin1 were 0.310 and 0.122-0.792 (p<.05). CONCLUSION: The -667T
      genetic variants in the Pin1 promoter contribute to an increased risk of CKD SHPT
      and may be biomarkers of susceptibility to CKD SHPT.

PMID- 27876427
TI  - FMR1 premutation: not only important in premature ovarian failure but also in
      diminished ovarian reserve.
AB  - It is recognized that FMR1 premutation expansions are associated with premature
      ovarian failure (POF), but their role in diminished ovarian reserve (DOR) is not
      clearly established. Moreover, the impact of smaller repeats at the boundary of
      premutation and normal is less clear. Therefore, we have compared the frequency
      of these intermediate (45-54 repeats) and premutation (>55) sized FMR1 CGG
      repeats among a patients group including 188 DOR and 173 POF women and 200
      controls. FSH and LH concentrations were also compared between intermediate and
      premutation ranges in patients. The 5' UTR of FMR1 gene was amplified using PCR.
      The numbers of trinucleotide repeats were confirmed by the Sanger sequencing
      method. The frequency of premutation was higher in POF and DOR patients in
      comparison with controls, but the difference in the incidence of intermediate
      alleles was not statistically significant among these groups. The mean level of
      serum FSH was higher in patients with premutation than patients with intermediate
      alleles. Based on the current evidence, we concluded that intermediate-sized FMR1
      CGG repeat alleles should not be considered as a high-risk factor for POF and
      DOR.

PMID- 27876429
TI  - Can polyacrylic acid treat sexual dysfunction in women with breast cancer
      receiving tamoxifen?
AB  - OBJECTIVE: There is a lack of safety data supporting the use of hormone therapy
      in women who have had breast cancer and who have complained of genitourinary
      syndrome of menopause (GSM). The objective was to test the efficacy of two non
      hormonal therapies for vaginal dryness. METHODS: This was a randomized trial with
      52 women with breast cancer who were being treated with tamoxifen and who
      complained of vaginal dryness. The volunteers answered two questionnaires to
      evaluate sexual function (Female Sexual Function Index, FSFI) and a customized
      GSM questionnaire. The women were randomized into two groups: 25 (48.1%) in the
      polyacrylic acid group and 27 (51.9%) in the lubricant group, using either one of
      the treatments for 30 days, and after they were invited to answer the
      questionnaires again. RESULTS: There was improvement in the FSFI after both
      treatments. The polyacrylic acid group showed a decrease in sexual dysfunction
      from 96% to 24% (p < 0.0001) and the lubricant group showed a decrease from 88.9%
      to 55.6% (p = 0.0027). CONCLUSIONS: The results of this study showed that both
      treatments improved sexual function; however, polyacrylic acid was superior to
      the lubricant in treating sexual dysfunction.

PMID- 27876430
TI  - The social image of drinking - mass media campaigns may inadvertently increase
      binge drinking.
AB  - Mass media campaigns that promote responsible drinking are rarely tested for
      their usefulness in reducing heavy alcohol consumption. Existing campaigns that
      appeal to responsible drinking while simultaneously displaying young people in
      social drinking situations may even have paradoxical effects. To examine such
      possible effects, we drew on a real-world media campaign, which we systematically
      modified on the basis of recent prototype research. We pilot tested
      questionnaires (using n = 41 participants), developed two different sets of
      posters in the style of an existing campaign (n = 39) and investigated their
      effectiveness (n = 102). In the main study, young men were randomly assigned to
      one of three conditions: sociable or unsociable binge drinker prototype condition
      or a control group. Outcome variables were intention, behavioural willingness,
      attitude, subjective norm, self-efficacy, prototype evaluation and prototype
      similarity with respect to binge drinking. Binge drinking as a habit was included
      to control for the fact that habitual drinking in social situations is hard to
      overcome and poses a particular challenge to interventions. The manipulation
      check showed that the experimental variation (sociable vs. unsociable drinker
      prototype condition) was successful. Results of the main study showed that the
      sociable drinker prototype condition resulted in a higher willingness and - for
      those with less of a habit - a higher intention to binge drink the next weekend.
      The unsociable drinker prototype condition had no effects. The results imply that
      the social components of mass media campaigns might inadvertently exacerbate
      binge drinking in young men. We therefore advocate against campaigns including
      aspects of alcohol consumption that might be positively associated with drinker
      prototype perception. Finally, we provide suggestions for future research.

PMID- 27876428
TI  - DMP-1 attenuates oxidative stress and inhibits TGF-beta activation in rats with
      diabetic kidney disease.
AB  - INTRODUCTION: DMP-1 supplement has a satisfactory effect on diabetic kidney
      disease in patients with whether T1DM or T2DM. Oxidative stress and TGF-beta
      signal pathway activation are essential in the pathogenesis of DKD. We aim to
      investigate the effect of DMP-1 on oxidative stress and TGF-beta activation in
      rats with DKD. MATERIALS AND METHODS: Male Wistar rats were enrolled and randomly
      allocated into five groups: Control group, STZ group (60 mg/kg, ip), DMP-1 low
      dose group (0.5 g/kg/day, ig), DMP-1 medium dose group (1.0 g/kg/day, ig) and DMP
      1 high dose group (2.0 g/kg/day, ig). The levels of UREA, BUN, UCr, beta2-MG,
      mALB, NOS, CAT, MDA and T-AOC were measured after 8 weeks treatment. And rats'
      left kidneys were harvested to detect the expression of TGF-beta, Smad2/3 and
      Smad7 by immunohistochemical analysis. RESULTS: DMP-1 treatment has protective
      effects on kidney injury induced by STZ, which is demonstrated as following
      criteria: (1) a significant reduction in levels of UREA (p < 0.05), BUN (p <
      0.05), UCr (p < 0.05), beta2-MG (p < 0.05) and mALB (p < 0.05) in rats treated by
      DMP-1 compared with the ones injected with STZ only; (2) an apparent increment
      levels of NOS (p < 0.05), CAT (p < 0.05) and T-AOC (p < 0.05), while reduction in
      level of MDA (p < 0.05) in DMP-1 groups compared with STZ group; (3) a
      significant inhibition of TGF-beta and Smad2/3 overexpression induced by STZ in
      kidney tissue. What's more, DMP-1 can increase Smad7 expression. CONCLUSION: DMP
      1 could slow pathological process and protect kidney from DKD injury by
      decreasing oxidative stress and inhibiting TGF-beta signal pathway activation in
      rats.

PMID- 27876431
TI  - Cystatin C, vascular biomarkers and measured glomerular filtration rate in
      patients with unresponsive hypertensive phenotype: a pilot study.
AB  - BACKGROUND: Biomarkers are commonly used to estimate the presence of subclinical
      cardiovascular disease (CVD) in patients with essential arterial hypertension
      (HT). In addition to known association between cystatin C and glomerular
      filtration rate (GFR), elucidating the association between cystatin C and
      vascular biomarkers (intima-media thickness of common carotid arteries (CCIMT),
      carotid plaque and renal artery resistance index (RRI)) in patients with
      unresponsive hypertensive phenotype could be of significant clinical interest.
      METHODS: Participants (n = 200, median age 58 (52-64) years, 49% female) under
      treatment with antihypertensive drugs were stratified into two subgroups based on
      their blood pressure level as having responsive hypertension (RHT - compliant and
      responsive to treatment, n = 100), or nonresponsive (URHT - compliant but
      nonresponsive to treatment, n = 100). GFR was measured by isotopic (slope
      intercept) method (99m Tc diethylene triamine penta-acetic acid - mGFR). RESULTS:
      The URHT group had significantly higher median cystatin C serum concentration (p
      = 0.02) and CCIMT (p = 0.00) compared to the RHT group, with no significant
      difference in RRI (p = 0.51) and mGFR among subgroups [69.9 +/- 28.2 vs 76.74 +/-
      23.61 ml/min/1.73m2, p = 0.27]. In the URHT group, cystatin C was found to be
      associated with CCIMT (p = 0.02), hsCRP (p = 0.01) and duration of HT (p = 0.02),
      independently of mGFR and age. Independent predictors of URHT phenotype were
      CCIMT (p= 0.02) and hsCRP (p= 0.04). CONCLUSION: In addition to GFR, cystatin C
      serum concentration is positively and independently associated with CCIMT in
      patient with URHT phenotype and subclinical CVD. Prospective larger studies
      should further investigate the clinical importance of this relationship.

PMID- 27876433
TI  - Corrigendum.

PMID- 27876432
TI  - Routine deferred computed tomography for patients with suspected urolithiasis is
      low-value healthcare.
AB  - OBJECTIVE: The aim of this study was to investigate the benefits of deferred
      routine computed tomography of the kidneys, ureters and bladder (CT KUB) for
      patients with a self-limiting episode of suspected urolithiasis. MATERIALS AND
      METHODS: The study comprised a case series of consecutive patients examined with
      deferred routine CT KUB for control of suspected urolithiasis. Patients examined
      with CT KUB at the University Hospital of North Norway, between 1 January 2010
      and 31 December 2013, were included. The final analysis included 189 CT KUBs
      (response rate 48%). All data were extracted from the patient case files. The
      primary endpoint was the proportion of asymptomatic patients with a confirmed
      diagnosis of urolithiasis on CT KUB that led to surgical intervention within 1
      year from the initial CT scan. RESULTS: At the time of CT KUB, 171 patients (90%)
      were asymptomatic, of whom three (1.8%) were treated. Urolithiasis was confirmed
      on CT KUB in 23% of asymptomatic patients. CONCLUSION: Deferred CT KUB did not
      alter the clinical outcome for the great majority of asymptomatic patients. The
      majority of patients who received adequate pain relief in primary care remained
      asymptomatic, and did not need specialized healthcare. Refraining from CT KUB
      involves little risk. Deferred CT KUB for patients with suspected urolithiasis is
      a low-value healthcare service.

PMID- 27876434
TI  - Testosterone/estradiol ratio, is it useful in the diagnosis of erectile
      dysfunction and low sexual desire?
AB  - Erectile dysfunction and low sexual desire are multifactorial diseases. The
      decrease in testosterone levels is one of the causes, but the effect of estradiol
      is not well known. Moreover, study has shown that the testosterone/estradiol
      ratio has more influence over sexuality than does estradiol alone. The aim of the
      study was to determine whether the balance between testosterone and estradiol has
      any relation to some aspects of sexual function. It was an ambispective study of
      230 patients with urological problems unrelated to sexuality. They underwent a
      detailed history and hormone study including total, free, bioavailable
      testosterone and estradiol. They completed the Sexual Health Inventory for Men
      and questions 11 and 12 of the IIEF15 were used to assess impairment in sexual
      desire. The T/E ratio was calculated, and the relationship between the different
      parameters and erectile function and sexual desire were studied by univariate and
      multivariate analysis. The mean age was 66.32 +/- 8.17 years. The percentage of
      patients with erectile dysfunction was 60.9% (7% severe, 14.3% moderate, 12.6%
      mild to moderate and 27% mild) and decreased sexual desire was 46.5%. Age, free
      and biodisponible testosteron were the only variables with a positive linear
      association with erectile dysfunction and decreased sexual desire. Age was the
      only independent variable for both, erectile dysfunction and sexual desire, in
      the multiple linear regression. There was no association between a
      testosterone/estradiol imbalance and an alteration in erectile function and
      sexual desire. Consequently, in the clinical study of these patients, it is not
      necessary to request estradiol in the laboratory analyses.

PMID- 27876435
TI  - Bioinspired approaches for cancer nanotheranostics.

PMID- 27876436
TI  - Targeted brain delivery nanoparticles for malignant gliomas.
AB  - Brain tumors display the highest mortality rates of all childhood cancers, and
      over the last decade its prevalence has steadily increased in elderly. To date,
      effective treatments for brain tumors and particularly for malignant gliomas
      remain a challenge mainly due to the low permeability and high selectivity of the
      blood-brain barrier (BBB) to conventional anticancer drugs. In recent years, the
      elucidation of the cellular mechanisms involved in the transport of substances
      into the brain has boosted the development of therapeutic-targeted nanoparticles
      (NPs) with the ability to cross the BBB. Here, we present a comprehensive
      overview of the available therapeutic strategies developed against malignant
      gliomas based on 'actively targeted' NPs, the challenges of crossing the BBB and
      blood-brain tumor barrier as well as its mechanisms and a critical assessment of
      clinical studies that have used targeted NPs for the treatment of malignant
      gliomas. Finally, we discuss the potential of actively targeted NP-based
      strategies in clinical settings, its possible side effects and future directions
      for therapeutic applications. First draft submitted: 4 October 2016; Accepted for
      publication: 14 October 2016; Published online: 23 November 2016.

PMID- 27876437
TI  - The content and distribution of steryl ferulates in wheat produced in Japan.
AB  - Oryzanol contained in rice bran is a complex mixture of steryl ferulates (SFs)
      with many identified health benefits. Recently, SF has been shown to exist in
      other cereals such as wheat, rye, and corn. In this study, SFs in several wheats
      produced in Japan were analyzed. For instance, SF content of whole wheat grain,
      Yumekaori (Japan) was 15.2 +/- 1.4 mg-oryzanol-equivalent/100 g grain, while that
      of the imported one, 1CW (Canada) was 11.4 +/- 1.3 mg-oryzanol-equivalent/100 g
      grain. The main SF components in the examined wheats were campesteryl ferulate,
      campestanyl ferulate, and sitostanyl ferulate. SF distribution in whole wheat
      grain was investigated using 14 fractions produced by a conventional test milling
      machine. SF was intensively accumulated in the four bran fractions (24 - 95 mg
      oryzanol-equivalent/100 g bran fraction). These results suggest that the wheat
      bran would be an important source of SF.

PMID- 27876438
TI  - Physicochemical characteristics of liposomes are decisive for their
      antirestenosis efficacy following local delivery.
AB  - AIM: To develop an ameliorated sirolimus (SIR) liposome for intramural delivery,
      the effects of various carrier physicochemical parameters on the antirestenosis
      efficacy were evaluated. MATERIALS & METHODS: Different liposomes were prepared,
      characterized and administered to balloon injured rats (12 animal groups). Their
      efficacies were investigated using morphometric, immunohistochemical and in vivo
      computed tomography imaging analyses. RESULTS: The antirestenosis efficacy of SIR
      liposomes decreased in the following order: cationic 100 nm vesicles >= cationic
      60 nm vesicles > neutral 100 nm vesicles >= stealth 100 nm vesicles > anionic 100
      nm vesicles. The 100 ug SIR loaded in cationic liposomes showed almost no artery
      stenosis. CONCLUSION: Appropriate modulation of physicochemical characteristics
      makes it possible to optimize the liposomes for local delivery.

PMID- 27876440
TI  - Cannabis, alcohol use, psychological distress, and decision-making style.
AB  - INTRODUCTION: There have been suggestions of hypofrontality in cannabis users. To
      understand cannabis-related differences in decisional processes, Janis and Mann's
      conflict model of decision making was applied to recreational cannabis smokers
      who varied in their alcohol use and level of psychological distress. METHOD: An
      online sample of recreational substance users (114 male, 119 female) completed
      the Melbourne Decision Making Questionnaire, the Alcohol Use Disorders
      Identification Test (AUDIT), Kessler's Psychological Distress Scale (K10), and
      the Severity of Dependence Scale (SDS) for cannabis. RESULTS: Multivariate
      analysis of variance examined self-reported decision-making styles as a function
      of gender, recent cannabis use, risky alcohol consumption, and levels of
      psychological distress. Psychological distress was associated with lower
      decisional self-esteem and higher levels of procrastination and buck-passing.
      There were gender differences associated with cannabis use. Female cannabis users
      reported higher levels of hypervigilance, while male cannabis users reported
      lower levels of buck-passing. CONCLUSIONS: Although there was little indication
      of an avoidant decisional style in cannabis users, the results suggest that
      cannabis affects decisional processes, contributing to panic in females and
      impulsivity in males.

PMID- 27876441
TI  - Imaging-guided revival of nanomedicine?

PMID- 27876442
TI  - Using magnetoferritin nanoprobes for both nuclear and magnetic-resonance imaging.

PMID- 27876443
TI  - Are we certain about which measure of intolerance of uncertainty to use yet?
AB  - Intolerance of Uncertainty (IU) has been understood as a dispositional tendency
      to view the presence of negative events as unacceptable and threatening,
      regardless of the likelihood of those events occurring. The preference over the
      12-item vs. 27-item of the IUS has been central to debate. The goals of the
      present study were to evaluate two competing models of measuring IU with model
      fitting analyses and explore model invariance of gender (e.g. men vs. women). A
      sample of 980 individuals completed an online IUS survey. Results indicated that
      the two-factor short-form model provided better fit to the data compared to the
      full-length two-factor model proposed by. Results also indicated that the short
      form IUS is gender invariant, suggesting acceptable use among men and women.
      These findings provide further support of a two-factor structure and suggest that
      the IUS is appropriate for men and women.

PMID- 27876444
TI  - The functional neuroanatomy of verbal memory in Alzheimer's disease: [18F]-Fluoro
      2-deoxy-D-glucose positron emission tomography (FDG-PET) correlates of recency
      and recognition memory.
AB  - INTRODUCTION: The objective of this study was to distinguish the functional
      neuroanatomy of verbal learning and recognition in Alzheimer's disease (AD) using
      the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word
      Learning task. METHOD: In 81 Veterans diagnosed with dementia due to AD, we
      conducted a cluster-based correlation analysis to assess the relationships
      between recency and recognition memory scores from the CERAD Word Learning Task
      and cortical metabolic activity measured using [18F]-fluoro-2-deoxy-D-glucose
      positron emission tomography (FDG-PET). RESULTS: AD patients (Mini-Mental State
      Examination, MMSE mean = 20.2) performed significantly better on the recall of
      recency items during learning trials than of primacy and middle items. Recency
      memory was associated with cerebral metabolism in the left middle and inferior
      temporal gyri and left fusiform gyrus (p < .05 at the corrected cluster level).
      In contrast, recognition memory was correlated with metabolic activity in two
      clusters: (a) a large cluster that included the left hippocampus, parahippocampal
      gyrus, entorhinal cortex, anterior temporal lobe, and inferior and middle
      temporal gyri; (b) the bilateral orbitofrontal cortices (OFC). CONCLUSIONS: The
      present study further informs our understanding of the disparate functional
      neuroanatomy of recency memory and recognition memory in AD. We anticipated that
      the recency effect would be relatively preserved and associated with
      temporoparietal brain regions implicated in short-term verbal memory, while
      recognition memory would be associated with the medial temporal lobe and possibly
      the OFC. Consistent with our a priori hypotheses, list learning in our AD sample
      was characterized by a reduced primacy effect and a relatively spared recency
      effect; however, recency memory was associated with cerebral metabolism in
      inferior and lateral temporal regions associated with the semantic memory
      network, rather than regions associated with short-term verbal memory. The
      correlates of recognition memory included the medial temporal lobe and OFC,
      replicating prior studies.

PMID- 27876445
TI  - A review of the use of a systematic observation method in coaching research
      between 1997 and 2016.
AB  - A systematic observation method has been one of the most popularly employed
      methods in coaching research. Kahan's review of this method conducted between
      1975 and 1997 highlighted the key trends in this research, and offered
      methodological guidance for researchers wishing to use this method in their
      research. The purpose of this review was to provide an update of the use of a
      systematic observation method in coaching research and assess the extent to which
      the calls made by Kahan have been addressed. While in some respect this field of
      study has progressed (i.e., the introduction of qualitative methods), researchers
      adopting this method have failed to attend to many of the issues Kahan raised.
      For this method to continue to make a positive contribution towards the coaching
      research literature, researchers need to more critically reflect on how and why
      they are employing this method. At present, some of the decisions made by
      researchers who have conducted work in this area are not justified with a
      rationale. It is our intention that this review will serve as guidance for
      researchers and practitioners, and editors and reviewers of journals when
      attempting to assess the quality of this type of work.

PMID- 27876446
TI  - Gastrostomy tube placement is safe in advanced amyotrophic lateral sclerosis.
AB  - OBJECTIVES: To evaluate the safety and effect on survival of insertion of a
      gastrostomy tube (G-tube) in patients with amyotrophic lateral sclerosis (ALS)
      who have upright forced vital capacity (uFVC) <= 50% predicted. Current
      guidelines, which are based on higher rates of post-procedure complications in
      ALS patients with advanced respiratory dysfunction, have led to a recommendation
      to perform G-tube insertion before the FVC drops to <50% predicted, even when the
      patient has no significant dysphagia. METHODS: We assessed 41 ALS patients who
      received a G-tube, mostly by insertion of a percutaneous endoscopic gastrostomy
      (PEG) tube by a dedicated team that included a gastroenterologist and one of two
      anesthesiologists using Monitored Anesthesia Care with deep sedation, and 61
      patients who did not receive a G-tube. uFVC was <=50% predicted in 12 of 41
      patients who received a G-tube and in 18 of 61 who did not. RESULTS: The
      procedure was safe regardless of FVC status, with low rates of post-operative
      complications in both low and high FVC groups. There was no survival benefit for
      patients who received a G-tube when compared with those who did not. DISCUSSION:
      PEG insertion is safe in ALS patients with significant respiratory muscle
      weakness when performed by a dedicated team, which suggests that the
      recommendation for G-tube placement should not be based on the patient's
      respiratory status.

PMID- 27876447
TI  - Coating microbubbles with nanoparticles for medical imaging and drug delivery.

PMID- 27876449
TI  - Reduction in spasticity in stroke patient with paraffin therapy.
AB  - PURPOSE: The aim of the study was to confirm whether paraffin therapy offer
      clinical value in the treatment of spasticity due to stroke. METHODS: Fifty-two
      patients with spasticity in the upper limb were included. The patients were
      randomized into the experimental group with paraffin therapy (n = 27) and the
      control group with placebo therapy (n = 25). The outcome measures besides
      temperature examination were undertaken at time points of 0 (T0), 2 (T1) and 4
      weeks (T2) following therapy treatment. The extent of spasticity was measured
      using Modified Ashworth Score (MAS) during passive movement at the shoulder,
      elbow, wrist and finger joints. Visual analogue scale (VAS) was used to evaluate
      the hemiplegic upper limb pain and functional activity of the upper limb motor
      function was evaluated by Brunnstrom recovery stage. All adverse events were
      recorded. RESULTS: MAS decreased significantly in Exp group compared with Con
      group, at the time points of T1 and T2, both before and immediately after
      paraffin therapy. Paraffin treatment failed to show remarkable improvement in
      pain compared with placebo-treated patient at movement at any time point. But VAS
      in Exp exhibited a tendency to decrease over time in shoulder, elbow, wrist and
      hand. With regard to the Brunnstrom score, patients in Exp showed significant
      improvement at the end of trial compared to the beginning. The values of
      temperature showed significant increment immediately after paraffin therapy at
      each time point in Exp group. CONCLUSION: Paraffin therapy may be a kind of
      noninvasive, promising method to reduce spasticity of stroke patients.

PMID- 27876450
TI  - Intraductal papillary neoplasm of the bile duct: a case report.
AB  - Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile
      duct tumors, characterized by papillary growth within the bile duct lumen and is
      regarded as a biliary counterpart of intraductal papillary mucinous neoplasm
      (IPMN) of the pancreas. IPNBs are mainly found in patients from Far Eastern
      areas, where hepatolithiasis and clonorchiasis are endemic. The Western
      experience, however, remains limited. In this article, we report a 56-year-old
      man, referred to our hospital because of deranged liver function tests. Further
      imaging modalities showed a cystic lesion of 9 cm diameter, arising from the left
      hepatic duct. Inlying was a heterogeneous, lobulated mass. The patient underwent
      a left hemihepatectomy and adjuvant chemotherapy. Despite recent advanced
      technologies, diagnosis of IPNB is still challenging, especially in western
      countries due to its rarity. Early identification and resection of lesions, even
      in asymptomatic or minimally symptomatic patients, are however important
      prognostic factors.

PMID- 27876451
TI  - Leukocytosis and neutrophilia after laparoscopic gastric plication.
AB  - BACKGROUND: Laparoscopic gastric plication (LGP) is a relatively novel bariatric
      surgery technique. We have encountered a noticeable proportion of our LGP
      patients with findings such as leukocytosis and neutrophilia and hypothesized
      that they are part of normal body response to the operation. OBJECTIVE: To
      evaluate the prevalence and clinical importance of leukocytosis, neutrophilia and
      abnormal vital signs in patients undergoing LGP during postoperative period.
      METHODS: Forty-four consecutive LGP patients were prospectively followed for 3
      months. Records of 44 laparoscopic cholecystectomy patients were also reviewed
      for comparison. Preoperative and postoperative laboratory test were performed.
      Minor and major complications were recorded during the study period. RESULTS:
      Mean body mass index (BMI) and age were 37and 42.5, respectively. Mean hospital
      stay was 3.6 days (range: 3-8 days). Leukocytosis and neutrophilia were detected
      in 63% and 72% of the LGP patients, respectively, 48 h after the procedure.
      Whereas, after cholecystectomy only 38.5% and 18% of patients had leukocytosis
      and neutrophilia, respectively. 25% of the patients suffered from at least one
      minor complication after LGP. There was no mortality. CONCLUSIONS: Leukocytosis
      and neutrophilia are very common after LGP in both the complicated and
      uncomplicated cases, and may be a part of normal response to surgery.

PMID- 27876452
TI  - Comparison of excursive occlusal force parameters in post-orthodontic and non
      orthodontic subjects using T-Scan(r) III.
AB  - OBJECTIVE: Published studies indicate that orthodontically treated patients
      demonstrate increased posterior occlusal friction contributing to
      temporomandibular disorder (TMD) symptoms. This study investigated measured
      excursive movement occlusal contact parameters and their association with TMD
      symptoms between non- and post-orthodontic subjects. METHODS: Twenty-five post
      orthodontic and 25 non-orthodontic subjects underwent T-Scan(r) computerized
      occlusal analysis to determine their disclusion time (DT), the excursive
      frictional contacts, and occlusal scheme. Each subject answered a TMD
      questionnaire to determine the presence or absence of TMD symptoms. Statistical
      analysis compared the within group and between group differences (p < 0.05).
      RESULTS: Statistically significant differences were observed in the disclusion
      time: DT = 2.69 s in the post-orthodontic and 1.36 s in the non-orthodontic
      group. In the non-orthodontic group, 72.7% working and 27.3% non-working side
      contacts were seen, while in the post-orthodontic group, (near equal) 54.7%
      working and 45.3% non-working side contacts were seen. Presence of canine
      guidance was seen in 60% of the non-orthodontic group and 24% in the post
      orthodontic group. Seventy-two percent of the post orthodontics subjects
      presented with one or more TMD symptoms. CONCLUSION: Significantly longer
      disclusion time, higher posterior frictional contacts, and more TMD symptoms were
      observed in the post-orthodontic group, suggesting that orthodontic treatment
      increases posterior tooth friction. Computerized occlusal analysis is an
      objective diagnostic tool determining the quality of excursive movements
      following orthodontic treatment.

PMID- 27876448
TI  - Magnetic nanoparticles for precision oncology: theranostic magnetic iron oxide
      nanoparticles for image-guided and targeted cancer therapy.
AB  - Recent advances in the development of magnetic nanoparticles (MNPs) have shown
      promise in the development of new personalized therapeutic approaches for
      clinical management of cancer patients. The unique physicochemical properties of
      MNPs endow them with novel multifunctional capabilities for imaging, drug
      delivery and therapy, which are referred to as theranostics. To facilitate the
      translation of those theranostic MNPs into clinical applications, extensive
      efforts have been made on designing and improving biocompatibility, stability,
      safety, drug-loading ability, targeted delivery, imaging signal and thermal- or
      photodynamic response. In this review, we provide an overview of the
      physicochemical properties, toxicity and theranostic applications of MNPs with a
      focus on magnetic iron oxide nanoparticles.

PMID- 27876453
TI  - "I can't tell whether it's my hand": a pilot study of the neurophenomenology of
      body representation during the rubber hand illusion in trauma-related disorders.
AB  - BACKGROUND: Early traumatic experiences are thought to be causal factors in the
      development of trauma-related dissociative experiences, including
      depersonalization and derealization. The rubber hand illusion (RHI), a well-known
      paradigm that measures multi-sensorial integration of a rubber hand into one's
      own body representation, has been used to investigate alterations in the
      experience of body ownership and of body representation. Critically, however, it
      has never been studied in individuals with trauma-related disorders. OBJECTIVE:
      To investigate body representation distortions occurring in trauma-related
      disorders in response to the RHI. METHOD: The RHI was administered to three
      individuals with the dissociative subtype of posttraumatic stress disorder
      (PTSD), and subjective, behavioral, cardiovascular and skin conductance responses
      were recorded. RESULTS: Participants' subjective experiences of the RHI were
      differentiated and complex. The illusion was induced following both synchronous
      and asynchronous brushing and variably evoked subjective distress,
      depersonalization and derealization experiences, tonic immobility, increased
      physiological arousal and flashbacks. CONCLUSIONS: The present findings point
      towards the RHI as a strong provocation stimulus that elicits individual patterns
      of symptom presentation, including experiences of distress and dissociation, in
      individuals with trauma-related disorders, including the dissociative subtype of
      PTSD. HIGHLIGHTS OF THE ARTICLE: The rubber hand illusion (RHI) elicits distress,
      tonic immobility, depersonalization and derealization, and autonomic responses in
      individuals with trauma-related disorders, including the dissociative subtype of
      posttraumatic stress disorder (PTSD). RHI effects related to body
      misrepresentation may trigger altered experiences related to body ownership. The
      RHI represents a promising paradigm for studying the neurophenomenology of body
      distortion in individuals experiencing trauma-related altered states of
      consciousness (TRASC).

PMID- 27876454
TI  - Will the global HIV response fail gay and bisexual men and other men who have sex
      with men?
AB  - INTRODUCTION: Gay and bisexual men and other men who have sex with men are among
      the small number of groups for whom HIV remains uncontrolled worldwide. Although
      there have been recent and notable decreases in HIV incidence across several
      countries, prevalence and incidence is consistently higher or rising among men
      who have sex with men when compared with other groups. METHODS: In 2014, MSMGF
      (the Global Forum on MSM & HIV) conducted its third biennial Global Men's Health
      and Rights Study, an international, multilingual, web-based cross-sectional
      survey of men who have sex with men recruited through online convenience
      sampling. We tested hypothesized correlates (selected a priori) of successfully
      achieving each step along the HIV prevention and treatment continuum by fitting
      separate generalized estimating equation models adjusted for clustering by
      country in multivariate analyses. All models controlled for ability to meet basic
      financial needs, age, healthcare coverage, having a regular provider, region and
      country-level income. RESULTS: Higher provider discrimination and sexual stigma
      were associated with lower odds of perceived access to services, service
      utilization and virologic suppression. Conversely, accessing services from
      community-based organizations focused on lesbian, gay, bisexual and transgender
      people; greater engagement in gay community; and comfort with healthcare
      providers were associated with higher odds of achieving steps along the
      prevention and treatment continuum. CONCLUSIONS: To meet accelerated global HIV
      targets, global leaders must adopt a differentiated and bolder response, in
      keeping with current epidemiologic trends and community-based research. The HIV
      related needs of gay and bisexual men and other men who have sex with men must be
      addressed openly, quickly and with sufficient resources to support evidence
      based, community-led and human rights-affirming interventions at scale.

PMID- 27876455
TI  - Multiple morbidities in companion dogs: a novel model for investigating age
      related disease.
AB  - The proportion of men and women surviving over 65 years has been steadily
      increasing over the last century. In their later years, many of these individuals
      are afflicted with multiple chronic conditions, placing increasing pressure on
      healthcare systems. The accumulation of multiple health problems with advanced
      age is well documented, yet the causes are poorly understood. Animal models have
      long been employed in attempts to elucidate these complex mechanisms with limited
      success. Recently, the domestic dog has been proposed as a promising model of
      human aging for several reasons. Mean lifespan shows twofold variation across dog
      breeds. In addition, dogs closely share the environments of their owners, and
      substantial veterinary resources are dedicated to comprehensive diagnosis of
      conditions in dogs. However, while dogs are therefore useful for studying
      multimorbidity, little is known about how aging influences the accumulation of
      multiple concurrent disease conditions across dog breeds. The current study
      examines how age, body weight, and breed contribute to variation in
      multimorbidity in over 2,000 companion dogs visiting private veterinary clinics
      in England. In common with humans, we find that the number of diagnoses increases
      significantly with age in dogs. However, we find no significant weight or breed
      effects on morbidity number. This surprising result reveals that while breeds may
      vary in their average longevity and causes of death, their age-related
      trajectories of morbidities differ little, suggesting that age of onset of
      disease may be the source of variation in lifespan across breeds. Future studies
      with increased sample sizes and longitudinal monitoring may help us discern more
      breed-specific patterns in morbidity. Overall, the large increase in
      multimorbidity seen with age in dogs mirrors that seen in humans and lends even
      more credence to the value of companion dogs as models for human morbidity and
      mortality.

PMID- 27876456
TI  - A qualitative study of the current situation of elderly care in Iran: what can we
      do for the future?
AB  - BACKGROUND: With the successful improvement of global health systems and social
      security in societies, the world is now advancing toward aging. All countries
      have to face the phenomenon of population aging sooner or later depending on
      their degree of development; however, elderly care is predicted to soon become a
      major concern for developing countries such as Iran. OBJECTIVES: This study was
      conducted to identify the challenges of elderly care in Iran and to help
      policymakers develop roadmaps for the future through providing a clearer image of
      the current state of affairs in this area of healthcare. DESIGN: This study has
      adopted a framework approach to qualitative data analysis. For this purpose, 37
      semi-structured interviews were conducted in 2015 with a number of key informants
      in elderly care who were familiar with the process at macro-, meso-, and micro
      levels. Maximum variation purposive sampling was performed to select the study
      samples. A conceptual framework was designed using a review of the literature,
      and key issues were then identified for data analysis. RESULTS: The elderly care
      process yielded five major challenges, including policymaking, access, technical
      infrastructure, integrity and coordination, and health-based care services.
      DISCUSSION: According to the stakeholders of elderly care in Iran, the current
      care system is not well-suited for meeting the needs of the elderly, as the
      elderly tend to receive the services they need sporadically and in a non-coherent
      manner. Given the rapid growth of the elderly population in the coming decades,
      it is the authorities' job to concentrate on the challenges faced by the health
      system and to use foresight methods for the comprehensive and systematical
      management of the issue.

PMID- 27876457
TI  - Providers' perspectives on inbound medical tourism in Central America and the
      Caribbean: factors driving and inhibiting sector development and their health
      equity implications.
AB  - BACKGROUND: Many governments and health care providers worldwide are enthusiastic
      to develop medical tourism as a service export. Despite the popularity of this
      policy uptake, there is relatively little known about the specific local factors
      prospectively motivating and informing development of this sector. OBJECTIVE: To
      identify common social, economic, and health system factors shaping the
      development of medical tourism in three Central American and Caribbean countries
      and their health equity implications. DESIGN: In-depth, semi-structured
      interviews were conducted in Mexico, Guatemala, and Barbados with 150 health
      system stakeholders. Participants were recruited from private and public sectors
      working in various fields: trade and economic development, health services
      delivery, training and administration, and civil society. Transcribed interviews
      were coded using qualitative data management software, and thematic analysis was
      used to identify cross-cutting issues regarding the drivers and inhibitors of
      medical tourism development. RESULTS: Four common drivers of medical tourism
      development were identified: 1) unused capacity in existing private hospitals, 2)
      international portability of health insurance, vis-a-vis international hospital
      accreditation, 3) internationally trained physicians as both marketable assets
      and industry entrepreneurs, and 4) promotion of medical tourism by public export
      development corporations. Three common inhibitors for the development of the
      sector were also identified: 1) the high expense of market entry, 2) poor sector
      wide planning, and 3) structural socio-economic issues such as insecurity or
      relatively high business costs and financial risks. CONCLUSION: There are shared
      factors shaping the development of medical tourism in Central America and the
      Caribbean that help explain why it is being pursued by many hospitals and
      governments in the region. Development of the sector is primarily being driven by
      public investment promotion agencies and the private health sector seeking
      economic benefits with limited consideration and planning for the health equity
      concerns medical tourism raises.

PMID- 27876458
TI  - Relative abundance of G protein-coupled receptor 30 and localization in testis
      and epididymis of sheep at different developmental stages.
AB  - The G protein-coupled receptor 30 (GPR30) is a transmembrane estrogen receptor
      that binds to estrogen, and has been confirmed to have an important role in
      testicular cell proliferation and development. The main objective of this study
      was to examine GPR30 gene expression and localization in the testis and
      epididymis of sheep at different developmental stages. Testes, including the
      epididymis, were collected from Polled Dorset x Mongolian cross rams at one (n=4;
      wt), three (n=4; wt), six (n=4; wt), nine (n=4; wt) and 12 (n=4; wt) months of
      age. The 12-month-old hybrid crossbred sheep were exsanguinated via puncture of
      the jugular vein. Relative abundance of GPR30 mRNA was detected by quantitative
      PCR, and localization of the protein was examined by immunohistochemistry. Semi
      quantitative analysis of GPR30 protein was performed by western blotting. The
      relative abundance of GPR30 mRNA was similar in the epididymis tail for rams at
      6, 9, and 12mo of age. Further, relative abundance of GPR30 mRNA in the testes
      and caput epididymis of 1-, 3-, 6-, 9-, and 12-month-old crossbred rams did not
      increase with age. The GPR30 mRNA was detected in epididymal interstitial and
      principal cells, and in the epididymal cavity, spermatocytes, spermatogonial stem
      cells, Sertoli and Leydig cells, and spermatozoon of ram testes. Western blotting
      indicated the GPR30 protein was present in 9- and 12-month-old crossbred sheep
      corpus, cauda epididymis (P<0.05). The results suggest that relative abundance of
      GPR30 mRNA is time-dependent and localization-specific.

PMID- 27876459
TI  - Local and widespread hyperalgesia in female runners with patellofemoral pain are
      influenced by running volume.
AB  - OBJECTIVES: To compare pressure pain threshold (PPT) around the knee (local
      hyperalgesia) and at a site remote to the knee (widespread hyperalgesia) between
      female runners with and without patellofemoral pain (PFP); and to evaluate the
      relationship between running volume, self-reported knee function and PPT
      measures. DESIGN: Cross-sectional study. METHODS: Twenty female runners with PFP
      and twenty pain-free female runners participated in the study. PPTs were measured
      using a handheld pressure algometer at four sites in the patellar region:
      quadriceps tendon, medial patella, lateral patella and patellar tendon; and on
      the contralateral upper limb. Additionally, all participants were asked to report
      their average weekly running volume in a typical month and answer the anterior
      knee pain scale (AKPS) questionnaire. RESULTS: For all sites, female runners with
      PFP presented lower PPT measures in comparison with control group (P<0.017).
      There were negative correlations between AKPS and running volume (rho=-0.88;
      P<0.001) and between all PPTs and the running volume in the PFP group with
      correlation (rho) values ranging between -0.46 and -0.70 (P<0.022). There were
      positive correlations between all PPTs and AKPS with correlation (rho) value from
      0.50 to 0.69 (P<0.030). CONCLUSION: Lower PPTs locally and remote to the knee in
      female runners with PFP indicate the presence of local and widespread
      hyperalgesia. Additionally, this hyperalgesia, which is related to self-reported
      knee function, appears to be increased by greater running volumes. Development
      and evaluation of non-mechanical interventions for the management of running
      related PFP in females may be needed to address this apparent hyperalgesia.

PMID- 27876460
TI  - IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical
      activity in a phase 2a, randomized, placebo-controlled trial in patients with
      moderate-to-severe plaque psoriasis.
AB  - BACKGROUND: Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self
      nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such
      as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease
      severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs
      7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy
      of IMO-8400 in a first-in-patient phase 2 trial. METHODS: Forty-six psoriasis
      patients were randomly assigned to IMO-8400 in four dose levels or placebo for
      12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence
      of adverse events. Secondary, exploratory outcomes included changes in psoriasis
      area and severity index (PASI). RESULTS: IMO-8400 across all dose levels did not
      cause any serious or severe adverse events. The most common treatment-related
      adverse events were dose-dependent injection-site reactions. All IMO-8400 groups
      showed clinical improvement, but a clear dose-response relationship and
      statistically significant differences with placebo were not observed (P=0.26).
      Eleven (38%) of 29 subjects on IMO-8400 achieved >=50% PASI-reduction, compared
      to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated
      subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo.
      CONCLUSIONS: Short-term IMO-8400-treatment was well tolerated and reduced
      psoriasis severity. These findings warrant further investigation of endosomal TLR
      antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs.
      TRIAL REGISTRATION: EudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729.

PMID- 27876461
TI  - Neutrophil infiltration mediated by CXCL5 accumulation in the laryngeal squamous
      cell carcinoma microenvironment: A mechanism by which tumour cells escape immune
      surveillance.
AB  - The CXCL5 chemokine is important for neutrophil accumulation in tumour tissues.
      In this report, we attempted to clarify whether and how infiltrating tumour
      associated neutrophils (TANs) in laryngeal squamous cell carcinoma (LSCC) affect
      the proliferation and activation of T cells. We examined chemokine expression by
      real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and
      performed an immunohistochemical analysis of LSCC microarrays. The relationship
      between CXCL5 and CD66b (a neutrophil marker) was investigated by
      immunofluorescence staining. We found that CXCL5 was upregulated in LSCC tissues,
      whereas CXCL5 levels were decreased in LSCC patient serum. Furthermore, high
      levels of CXCL5 were significantly correlated with intratumoural neutrophil
      infiltration. Compared with peripheral blood neutrophils (PBNs), TANs
      significantly inhibited T cell proliferation and decreased IFN-gamma and TNF
      alpha secretion. These data suggest that excessive neutrophil infiltration is
      associated with advanced clinical stages of LSCC (T3 or T4, III or IV, and N1 or
      N2).

PMID- 27876462
TI  - Expression and clinicopathological significance of S100 calcium binding protein
      A2 in lung cancer patients of Chinese Han ethnicity.
AB  - BACKGROUND: S100 family of calcium-binding proteins plays a significant role in
      the process of many kinds of tumors, including lung cancer. As an important
      member of this family, S100 calcium binding protein A2 (S100A2) has been
      confirmed to be associated with many biological processes, and has an abnormal
      expression in non-small cell lung cancer (NSCLC). However, the S100A2 status in
      lung cancer is still controversial and undefined. METHODS: We evaluated the
      pattern and distribution of S100A2 in 109 cases of lung cancer, including five
      histological types (47 adenocarcinoma, 46 squamous cell carcinoma, 7 small cell
      carcinoma, 3 large cell carcinoma, and 6 atypical carcinoid), and 30 cases of
      paired adjacent normal lung tissues by means of immunohistochemistry. RESULTS:
      Compared with the normal tissues (0/30), S100A2 experienced a dramatically upward
      trend of positive expression in lung cancer, with a positive rate of 68/109
      (P<0.001). Specifically, squamous cell carcinoma, with 34/12, had the highest
      expression ratio, followed by large cell carcinoma (2/1), adenocarcinoma (31/16),
      and atypical carcinoid (1/5) respectively, while no S100A2 protein was detected
      in small cell carcinoma. Meanwhile, we firstly demonstrated that the high
      expression of S100A2 was significantly associated with the incidence of lymph
      node metastasis in adenocarcinoma (P=0.013). CONCLUSIONS: The association between
      high S100A2 expression and NSCLC at the level of tissue, and S100A2 may serve as
      an effective biomarker for the diagnosis and prognosis of NSCLC in future.

PMID- 27876464
TI  - Muller stem cell dependent retinal regeneration.
AB  - Muller Stem cells to treat ocular diseases has triggered enthusiasm across all
      medical and scientific communities. Recent development in the field of stem cells
      has widened the prospects of applying cell based therapies to regenerate ocular
      tissues that have been irreversibly damaged by disease or injury. Ocular tissues
      such as the lens and the retina are now known to possess cell having remarkable
      regenerative abilities. Recent studies have shown that the Muller glia, a cell
      found in all vertebrate retinas, is the primary source of new neurons, and
      therefore are considered as the cellular basis for retinal regeneration in
      mammalian retinas. Here, we review the current status of retinal regeneration of
      the human eye by Muller stem cells. This review elucidates the current status of
      retinal regeneration by Muller stem cells, along with major retinal degenerative
      diseases where these stem cells play regenerative role in retinal repair and
      replacement.

PMID- 27876463
TI  - Re-evaluating the sensitivity of the rabbit infectivity test for Treponema
      pallidum in modern era.
AB  - BACKGROUND: The rabbit infectivity test (RIT) was previously described as a
      highly-sensitive method for clinically detecting Treponema pallidum. But our
      primary study indicated this result may have changed in current antibiotics era.
      METHODS: By inoculating rabbits testis with cerebrospinal fluid (CSF) (n=63) and
      exudate from hard chancre lesions (n=13), we re-evaluated the sensitivity of RIT
      in modern era. All isolated T. pallidum strains from the RIT were performed for
      the strain type based on "CDC subtype/tp0548" method. Chi-square and Fisher's
      exact tests were used to determine the statistical significance of differences
      across data sets. RESULTS: Result indicated that 2 of 63 CSF (2/63, 3.17%) and 5
      of 13 lesion exudate samples (5/13, 38.47%) were positive in the RIT, with a much
      longer time to detection for CSF samples. Only 1 of 28 samples from patients who
      admitted treatment with antibiotics prior to clinical exam was positive in the
      RIT; while 6 of 48 patients, who admitted no recent exposure to antibiotics or
      was unclear about the medical history, were positive in RIT. DNA sequence
      analysis revealed 6 strains of 14d/f subtype and one strain of 14a/f subtype.
      CONCLUSIONS: In conclusions, RIT is no longer a highly sensitive method for
      detecting T. pallidum in clinical samples as before, and is not inadequately
      considered to be a reference method for measuring the sensitivity of other new
      methods, such as the PCR. These data represent the first reexamination of the
      sensitivity of RIT in the post-antibiotic era with a large clinical sample.

PMID- 27876465
TI  - Is There Still a Role for Irrigation and Debridement With Liner Exchange in Acute
      Periprosthetic Total Knee Infection?
AB  - BACKGROUND: Periprosthetic joint infection (PJI) is an important cause of failure
      in total knee arthroplasty. Irrigation and debridement including liner exchange
      (I&D/L) success rates have varied for acute PJI. The purpose of this study is to
      present results of a specific protocol for I&D/L with retention of total knee
      arthroplasty components. METHODS: Sixty-seven consecutive I&D/L patients were
      retrospectively evaluated. Inclusion criteria for I&D/L were as follows: fewer
      than 3 weeks of symptoms, no immunologic compromise, intact soft tissue sleeve,
      and well-fixed components. I&D/L consisted of extensive synovectomy; irrigation
      with 3 L each of betadine, Dakin's, bacitracin, and normal saline solutions; and
      exchange of the polyethylene component. Postoperatively, all patients were
      treated with intravenous antibiotics. Infection was considered eradicated if the
      wound healed without persistent drainage, there was no residual pain or evidence
      of infection. RESULTS: Forty-six patients (68.66%) had successful infection
      eradication regardless of bacterial strain. Those with methicillin-resistant
      Staphylococcus aureus (MRSA) had an 80% failure rate and those with Pseudomonas
      aeruginosa had a 66.67% failure rate. The success rate for bacteria other than
      MRSA and Pseudomonas was 85.25%. CONCLUSION: Our protocol for I&D/L was
      successful in the majority of patients who met strict criteria. We recommend that
      PJI patients with MRSA or P aeruginosa not undergo I&D/L and be treated with 2
      stage revision. For nearly all other patients, our protocol avoids the cost and
      patient morbidity of a 2-stage revision.

PMID- 27876466
TI  - Primary Angioplasty in a Single Coronary Artery.

PMID- 27876468
TI  - Erratum.

PMID- 27876467
TI  - A review on tacrine-based scaffolds as multi-target drugs (MTDLs) for Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a multifactorial neurological disorder among elderly
      people and combinatorial factors such as genetic, lifestyle, and environmental
      are involved in onset and disease progression. It has been demonstrated that loss
      of cholinergic transmission is one of the most significant causes of AD. One
      strategy currently being investigated for the development of new therapeutics
      relates to the enhancement of cholinergic system through several ways. At this
      juncture, anticholinesterase inhibitors have absorbed lots of attention and
      different marketed drugs such as donepezil, rivastigmine, tacrine, and
      galantamine have been developed. 9-Amino-1,2,3,4-tetrahydroacridine known as
      tacrine was introduced in 1945 as an efficient anticholinesterase agent. The
      mechanism of action of tacrine was proved to inhibit the metabolism of
      acetylcholine and therefore extending its activity and raising levels in the
      cerebral cortex. However, extensive use of tacrine was limited since it showed
      various side effects and toxicity. Thus, lots of efforts were carried out to
      prepare tacrine analogues to overcome the related adverse effects. This review
      describes differently synthesized tacrine-based scaffolds as cholinesterase
      inhibitors to manage Alzheimer's disease (AD).

PMID- 27876470
TI  - Mechanotransduction via the nuclear envelope: a distant reflection of the cell
      surface.
AB  - As the largest and stiffest organelle in the cell, the nucleus can be subjected
      to significant forces generated by the cytoskeleton to adjust its shape and
      position, and accommodate the cellular machinery during cell migration,
      differentiation or division. As it was anticipated, recent work showed that
      mechanosensitive mechanisms exist in the nucleus and regulate its structure and
      function in response to mechanical force. While the molecular mechanisms that
      mediate this response are only beginning to be elucidated, the nuclear envelope
      seems to play a central role in this process. Here, we review these nuclear
      mechanosensitive mechanisms and highlight their functional homology with those
      located at the cell surface. Additionally, we discuss how these nuclear envelope
      mechanisms function during adhesion and migration, and how they participate in
      cytoskeletal organization, via direct physical contact or signaling event
      regulation.

PMID- 27876469
TI  - Sarcopenic Obesity Definitions by Body Composition and Mortality in the
      Hemodialysis Patients.
AB  - OBJECTIVE: Sarcopenic obesity (SO), a combination of low muscle mass and high fat
      mass, is considered as risk factor for mortality in general population. It is
      unclear if SO affects mortality in maintenance hemodialysis (MHD) patients. In
      this study, we aimed to determine whether body composition as assessed by
      currently available SO definitions is related to all-cause mortality in MHD
      subjects. We also examined the impact of applying different definitions on the
      prevalence of SO in our MHD database. DESIGN: Retrospective analysis. SUBJECTS:
      Adult patients on MHD for at least 3 months with no acute illness studied in the
      clinical research center between 2003 and 2011. INTERVENTION: Assessment of body
      composition was performed using dual energy x-ray absorptiometry. SO
      (appendicular skeletal mass: arm lean mass + leg lean mass and fat mass) was
      defined according to Baumgartner definition, Janssen criteria 1, and Janssen
      criteria 2. MAIN OUTCOME MEASURE: All-cause mortality and prevalence of SO.
      Patient deaths were ascertained from medical records and United States social
      security death index. RESULTS: Of 122 participants, 62% were male; mean age was
      46 years (interquartile range: 40, 54) in men and 50 years (44, 61) in women.
      Prevalence of SO ranged from 12% to 62% in men and 2% to 74% in female according
      to different definitions. SO prevalence was lowest using the Baumgartner criteria
      (all: 8%, men 12%, women: 2%) and highest according to the Janssen criteria 2
      (all: 57%, men 46%, women 74%). There were 45 deaths during a median follow-up
      period of 44 (20, 76) months. SO by any definition was not statistically
      significantly associated with mortality during follow-up. CONCLUSIONS: The
      current SO definitions are not applicable to predict increased risk of death in
      MHD patients. We found high degree of variation in the rates of SO when using
      different definitions. Future studies should focus on establishing MHD population
      specific thresholds of muscle mass and adiposity for accurate prognostication.

PMID- 27876471
TI  - Cobalamin and folate protect mitochondrial and contractile functions in a murine
      model of cardiac pressure overload.
AB  - PGC-1alpha, a key regulator of energy metabolism, seems to be a relevant
      therapeutic target to rectify the energy deficit observed in heart failure (HF).
      Since our previous work has shown positive effects of cobalamin (Cb) on PGC
      1alpha cascade, we investigate the protective role of Cb in pressure overload
      induced myocardial dysfunction. Mice were fed with normal diet (ND) or with Cb
      and folate supplemented diet (SD) 3weeks before and 4weeks after transverse
      aortic constriction (TAC). At the end, left ventricle hypertrophy and drop of
      ejection fraction were significantly lower in SD mice than in ND mice.
      Alterations in mitochondrial oxidative capacity, fatty acid oxidation and
      mitochondrial biogenesis transcription cascade were markedly improved by SD. In
      SD-TAC mice, lower expression level of the acetyltransferase GCN5 and
      upregulation of the methyltransferase PRMT1 were associated with a lower protein
      acetylation and a higher protein methylation levels. This was accompanied by a
      sustained expression of genes involved in mitochondrial biogenesis transcription
      cascade (Tfam, Nrf2, Cox1 and Cox4) after TAC in SD mice, suggesting a preserved
      activation of PGC-1alpha; this could be at least partly due to corrected
      acetylation/methylation status of this co-activator. The beneficial effect of the
      treatment would not be due to an effect of Cb and folate on oxidative stress or
      on homocysteinemia, which were unchanged by SD. These results showed that Cb and
      folate could protect the failing heart by preserving energy status through
      maintenance of mitochondrial biogenesis. It reinforces the concept of a metabolic
      therapy of HF.

PMID- 27876472
TI  - Evaluation of recombinant antigens in combination and single formula for
      diagnosis of feline toxoplasmosis.
AB  - Cats are the only definitive hosts of Toxoplasma gondii and constitute an
      essential source of infection to all warm blooded animals and humans. Diagnosis
      of T. gondii infection in cats is fundamental for proper management and control
      of infection in humans and animals. In the current study, we have evaluated the
      diagnostic performance of tachyzoite lysate antigen (TLA) and different T. gondii
      recombinant antigens including surface antigen 2 (SAG2), dense granule proteins
      2, 6, 7, 15 (GRA2, GRA6, GRA7, GRA15) and microneme 10 protein (MIC10) in
      immunoglobulin G enzyme linked-immunosorbent assay (IgG ELISA) using cat serum
      samples, with reference to latex agglutination test (LAT). Remarkably, TLA showed
      better performance than other recombinant antigens in IgG ELISAs as compared to
      LAT, with concordance and Kappa values of 94.27% and 0.93, respectively.
      Furthermore, to improve the reactivity of the recombinant antigens, we have
      developed IgG ELISAs using different combinations with these recombinant
      antigens. Strikingly, a combination of SAG2 and GRAs has relatively similar
      performance as TLA evidenced by concordance and Kappa values of 94.27% and 0.81,
      respectively. The developed ELISA with a combination of recombinant antigens can
      be used as a promising diagnostic tool for routine testing of T. gondii infection
      and mass screening in cats. The major advantages of this assay are the high
      sensitivity and specificity, lower cost, safer production and easiness of
      standardization in various laboratories worldwide.

PMID- 27876474
TI  - From the maximum tolerable to the minimum effective treatment: The Umberto
      Veronesi's life commitment to breast cancer care.

PMID- 27876473
TI  - Expression of truncated Babesia microti apical membrane protein 1 and rhoptry
      neck protein 2 and evaluation of their protective efficacy.
AB  - In this study, we evaluated the protective effect of recombinant Babesia microti
      apical membrane protein 1 (rBmAMA1) and rhoptry neck protein 2 (rBmRON2) against
      B. microti infection using a hamster model. The genes encoding the predicted
      domains I and II of BmAMA1 and the gene encoding the predicted transmembrane
      regions 2 and 3 of BmRON2 were expressed as His fusion recombinant proteins in
      Escherichia coli. Three groups with 5 hamsters in each group were immunized with
      rBmAMA1, rBmRON2 and rBmAMA1+rBmRON2, then challenged with B. microti. The result
      showed that only the group immunized with rBmAMA1+rBmRON2 exhibited limited
      protection against B. microti challenge infection, characterized by significant
      decreased of parasitemia and higher hematocrit values from day 6-10 post
      challenge infection. However, there was no significant difference in the groups
      immunized with rBmAMA1 or rBmRON2 alone. The absence of a significant difference
      in the total amount of antibodies against rBmAMA1 and rBmRON2 between the group
      immunized with single and combined proteins. This result suggests that the
      protection cannot be solely attributed to the quantity of antibodies produced,
      but also to their ability to target important epitopes from both antigens. These
      results suggest that combined immunization with rBmAMA1 and rBmRON2 is a
      promising strategy against B. microti.

PMID- 27876475
TI  - Microwave assisted synthesis of novel tetrazole/sulfonamide derivatives based on
      octahydroacridine, xanthene and chromene skeletons as inhibitors of the carbonic
      anhydrases isoforms I, II, IV and VII.
AB  - The synthesis of novel tetrazole/sulfonamide derivatives based on
      octahydroacridine, xanthene and chromene scaffold by using microwave (MW)
      assisted techniques is reported in this study. These synthesized hybrid compounds
      were assayed for the inhibition of carbonic anhydrase (CA, EC 4.2.1.1). The
      inhibitory activities were determined against three cytosolic human isoforms (hCA
      I, II and VII) and one membrane-associated (hCA IV) isoform. Some of the newly
      synthesized sulfonamides showed micromolar to nanomolar inhibitory activity
      against these enzymes.

PMID- 27876476
TI  - Studies relating to the synthesis, enzymatic reduction and cytotoxicity of a
      series of nitroaromatic prodrugs.
AB  - A series of N-nitroarylated-3-chloromethyl-1,2,3,4-tetrahydroisoquinoline
      derivatives, several of which also possessed a trifluoromethyl substituent, were
      prepared and assessed as potential nitroaromatic prodrugs. The enzymatic
      reduction of these compounds and their cytotoxicities were studied. The compounds
      were cytotoxic, but this is probably not related to their enzymatic reduction.

PMID- 27876477
TI  - Current Prescribing Practices for Skin and Soft Tissue Infections in Nursing
      Homes.
AB  - OBJECTIVES: Antibiotic stewardship has been called for across all sites of health
      care, including nursing homes (NHs). Skin and soft tissue infections (SSTIs) are
      the third most common indication for antibiotics in the NH, and so should be a
      focus of stewardship. This study audited medical records to identify signs and
      symptoms of SSTIs treated with antibiotics in relation to the McGeer criteria for
      surveillance, the Loeb minimum criteria for antibiotic initiation, and
      prescribing recommendations of the Infectious Disease Society of America. DESIGN:
      Cross-sectional study. SETTING: Thirty-one NHs in Southeastern United States.
      MEASUREMENTS: Chart data from a random sample of 161 antibiotic prescriptions for
      SSTIs were abstracted. To meet the McGeer criteria, pus was present at a
      suspected SSTI site, or at least four of the following findings were documented
      as present at the site: new or worsening warmth, redness, swelling, tenderness,
      serous drainage, or a constitutional finding. The Loeb minimum criteria for
      initiating antibiotics included findings of new or increasing purulent drainage
      at a suspected SSTI site or at least two of the following findings: fever or new
      or worsening redness, tenderness, warmth, or swelling at the suspected site.
      Audits also collected the name, route, and duration of the associated antibiotic.
      Analyses calculated the types of diagnoses and evaluated associations between
      published criteria and prescribing. RESULTS: Cellulitis, skin/soft tissue injury
      with infection, and abscess were diagnosed in 37% (N = 59), 18% (N = 29), and 16%
      (N = 26) of cases, respectively; 27% (N = 43) had less specific diagnoses. The
      McGeer criteria were met in 25% (N = 40), and the Loeb minimum criteria were met
      in 48% (N = 77) of cases. Doxycycline was the most frequently prescribed
      antibiotic. The mean treatment length was 9.6 days (standard deviation, 5.6), and
      the median length of treatment was 8.5 days (range, 3-45). CONCLUSION: SSTIs are
      not routinely diagnosed or treated according to recommended standards of care,
      and prescriptions for systemic antibiotics appear to be frequently initiated
      without regard to recommended definitions of infection or therapies for the
      associated diagnoses. These findings indicate that SSTIs present various
      opportunities to improve antibiotic stewardship.

PMID- 27876478
TI  - Physical Exercise Helped to Maintain and Restore Functioning in Chinese Older
      Adults With Mild Cognitive Impairment: A 5-Year Prospective Study of the Hong
      Kong Memory and Ageing Prospective Study (HK-MAPS).
AB  - OBJECTIVE: This study investigated the potential of physical exercise habit as a
      lifestyle modification against cognitive and functional decline at the community
      level. METHODS: A total of 454 community-dwelling Chinese older adults without
      dementia participated in the Hong Kong Memory and Ageing Prospective Study at
      baseline and follow-up at 5 years. Their cognitive and functional performances
      were assessed by the Cantonese version of the Mini-Mental State Examination
      (CMMSE) and the Chinese version of Disability Assessment in Dementia (DAD).
      Hierarchical multiple regression analyses were performed to examine whether
      physical exercise was a significant predictor of the follow-up CMMSE and DAD
      scores after controlling for the covariates. Subgroup analyses were performed
      with a group of 127 participants with mild cognitive impairment at baseline.
      RESULTS: Physical exercise habit was a significant predictor for both the follow
      up CMMSE scores and DAD scores. Participants with exercise habits of 5 years or
      more showed better cognitive and functional performances at follow-up.
      Participants who picked up exercise habits only after the baseline assessment
      also demonstrated better functioning at follow-up. The same patterns were
      observed in the subgroup analyses with the mild cognitive impairment group.
      CONCLUSION: Results suggested that prolonged exercise habit is required for
      positive effects on cognition to emerge, but benefits on functioning can be
      observed when individuals take up an exercise habit later in life or even after
      the beginning of cognitive decline. These findings are encouraging in promoting
      an exercise habit among older adults living in the community.

PMID- 27876479
TI  - Implications of Orthostatic Hypotension in Older Persons With and Without
      Diabetes.

PMID- 27876480
TI  - Noise dosimetry for tactical environments.
AB  - Noise exposure and the subsequent hearing loss are well documented aspects of
      military life. Numerous studies have indicated high rates of noise-induced
      hearing injury (NIHI) in active-duty service men and women, and recent statistics
      from the U.S. Department of Veterans Affairs indicate a population of veterans
      with hearing loss that is growing at an increasing rate. In an effort to minimize
      hearing loss, the U.S. Department of Defense (DoD) updated its Hearing
      Conservation Program in 2010, and also has recently revised the DoD Design
      Criteria Standard Noise Limits (MIL-STD-1474E) which defines allowable noise
      levels in the design of all military acquisitions including weapons and vehicles.
      Even with such mandates, it remains a challenge to accurately quantify the noise
      exposure experienced by a Warfighter over the course of a mission or training
      exercise, or even in a standard work day. Noise dosimeters are intended for
      exactly this purpose, but variations in device placement (e.g., free-field, on
      body, in/near-ear), hardware (e.g., microphone, analog-to-digital converter),
      measurement time (e.g., work day, 24-h), and dose metric calculations (e.g., time
      weighted energy, peak levels, Auditory Risk Units), as well as noise types (e.g.,
      continuous, intermittent, impulsive) can cause exposure measurements to be
      incomplete, inaccurate, or inappropriate for a given situation. This paper
      describes the design of a noise dosimeter capable of acquiring exposure data
      across tactical environments. Two generations of prototypes have been built at
      MIT Lincoln Laboratory with funding from the U.S. Army, Navy, and Marine Corps.
      Details related to hardware, signal processing, and testing efforts are provided,
      along with example tactical military noise data and lessons learned from early
      fieldings. Finally, we discuss the continued need to prioritize personalized
      dosimetry in order to improve models that predict or characterize the risk of
      auditory damage, to integrate dosimeters with hearing-protection devices, and to
      inform strategies and metrics for reducing NIHI.

PMID- 27876481
TI  - Physical Effects of Unilateral Mastectomy on Spine Deformity.
AB  - OBJECTIVE: Mastectomy is known to effect body posture after a change in the
      center of gravity of women due to a missing breast. Although previous studies on
      short-term postural changes in mastectomy patients using photogrammetry or Moire
      topography suggested ipsilateral inclination of the trunk, our clinical
      observations during breast reconstruction surgeries indicated a contralateral
      shoulder elevation in women with unilateral mastectomy. Because the change in
      body posture can affect spinal alignment, we aimed to evaluate the long-term
      physical effects of unilateral mastectomy on spine deformity by radiographic
      examination. METHODS: Posteroanterior chest radiographs of 60 women (mean age
      56.3 +/- 8.5 years) taken before and 12 months after the mastectomy were
      evaluated for Cobb angle and the presence or absence of a tilt from the midline
      in the coronal plane of vertebral body alignment. RESULTS: Cobb angle decreased
      in 14 and increased in 38 of 60 patients after unilateral mastectomy, and the
      angular change was found to be independent of the mastectomy side (P < .001). A
      shift in Cobb angle to the mastectomy side was observed in 11 of 53 patients (P >
      .05), whereas a statistically significant shift in Cobb angle to the opposite of
      the mastectomy side was observed in 33 of 53 patients (P < .001). The results of
      this observational retrospective study indicated long-term spinal deformation in
      women with unilateral mastectomy. Two patients with idiopathic scoliosis before
      mastectomy even developed scoliosis. CONCLUSION: We recommend informing the
      patients of the possible change in body posture in the long term, which should be
      supported or limited with physical therapy.

PMID- 27876482
TI  - Virtual collaboration, satisfaction, and trust between nurses in the tele-ICU and
      ICUs: Results of a multilevel analysis.
AB  - PURPOSE: The purpose of the study was to examine how tele-intensive care unit
      (tele-ICU) nurse characteristics and organizational characteristics influence
      tele-ICU nurses' trust and satisfaction of monitored bedside ICU nurses, and
      whether these influences are mediated by communication. MATERIALS AND METHODS:
      Data of tele-ICU characteristics and characteristics of the ICUs they monitored
      were collected at 5 tele-ICUs located throughout the country. One hundred ten
      tele-ICU nurses at those tele-ICUs completed a questionnaire containing items
      related to their characteristics and their trust, satisfaction, and perceived
      communication with monitored bedside nurses. We analyzed the data using a
      hierarchical path model, with communication variables entered as mediators.
      RESULTS: Many of the tele-ICU nurse characteristics (age, currently or previously
      worked at the monitored ICU, hours worked per week, and years as a ICU nurse) had
      statistically significant direct effects on perception of communication
      timeliness, accuracy, and openness, as well as trust and satisfaction with
      monitored bedside ICU nurses. Communication openness mediated the relationships
      of both working at a monitored ICU and being older (>=55) on satisfaction.
      Communication accuracy mediated the relationships of both a specialized monitored
      ICU and working at a monitored ICU on trust. CONCLUSIONS: Tele-ICUs and monitored
      ICUs should work to optimize communication so that trust can be established among
      the nurses.

PMID- 27876483
TI  - Opioid overdose leading to intensive care unit admission: Epidemiology and
      outcomes.

PMID- 27876484
TI  - Zika: A Missed Opportunity to Protect Women's Health and Prevent Unwanted
      Pregnancies.

PMID- 27876486
TI  - The role of food in the Polish migrant adjustment journey.
AB  - In 2015, there were 916,000 Poles living in the UK, making them the largest group
      of non-UK nationals at 16.5 percent of the population. Though increasingly
      research has focused on the consequences of this migration for both migrants
      themselves and the receiving country, little research has looked at food habits.
      This paper will explore the role of food in the Polish migrant adjustment
      journey. A qualitative approach was adopted, involving semi-structured interviews
      with nine Polish migrants. In this study, Polish migrants described the move to a
      new culture as a time of stress and loneliness. Due to a lack of money, they were
      forced to eat local food, which exacerbated their unease, as they found it to be
      tasteless and unhealthy. As soon as their financial situation improved, they
      reverted to a Polish diet, relying on ingredients brought from home, from London,
      or more recently, purchased from local Polish shops. This gave them comfort, and
      all participants acknowledged the vital role of food in their adjustment to life
      in a new culture.

PMID- 27876487
TI  - Fungal Mating in the Most Widespread Plant Symbionts?
AB  - Arbuscular mycorrhizal fungi (AMF) are relevant plant symbionts whose hyphae and
      spores carry hundreds of coexisting nuclei with supposedly divergent genomes but
      no sign of sexual reproduction. This unusual biology suggested that conventional
      fungal mating is not amendable to optimize strains for plant growth, but recent
      evidence of sexual-related nuclear inheritance in these organisms is now
      challenging this widespread notion. Here, we outline our knowledge of AMF
      genetics within a historical context, and discuss how past and new information in
      this area changed our understanding of AMF biology. We also highlight the mating
      related processes in AMF, and propose new research avenues and approaches that
      could lead to a better application of these organisms for agricultural and
      environmental practices.

PMID- 27876485
TI  - Cannabinoid receptors and TRPA1 on neuroprotection in a model of retinal
      ischemia.
AB  - Retinal ischemia is a pathological event present in several retinopathies such as
      diabetic retinopathy and glaucoma, leading to partial or full blindness with no
      effective treatment available. Since synthetic and endogenous cannabinoids have
      been studied as modulators of ischemic events in the central nervous system
      (CNS), the present study aimed to investigate the involvement of cannabinoid
      system in the cell death induced by ischemia in an avascular (chick) retina. We
      observed that chick retinal treatment with a combination of WIN 55212-2 and
      cannabinoid receptor antagonists (either AM251/O-2050 or AM630) decreased the
      release of lactate dehydrogenase (LDH) induced by retinal ischemia in an oxygen
      and glucose deprivation (OGD) model. Further, the increased availability of
      endocannabinoids together with cannabinoid receptor antagonists also had a
      neuroprotective effect. Surprisingly, retinal exposure to any of these drugs
      alone did not prevent the release of LDH stimulated by OGD. Since cannabinoids
      may also activate transient receptor potential (TRP) channels, we investigated
      the involvement of TRPA1 receptors (TRPA1) in retinal cell death induced by
      ischemic events. We demonstrated the presence of TRPA1 in the chick retina, and
      observed an increase in TRPA1 content after OGD, both by western blot and
      immunohistochemistry. In addition, the selective activation of TRPA1 by mustard
      oil (MO) did not worsen retinal LDH release induced by OGD, whereas the blockage
      of TRPA1 completely prevented the extravasation of cellular LDH in ischemic
      condition. Hence, these results show that during the ischemic event there is an
      augment of TRPA1, and activation of this receptor is important in cell death
      induction. The data also indicate that metabotropic cannabinoid receptors, both
      type 1 and 2, are not involved with the cell death found in the early stages of
      ischemia. Therefore, the study points to a potential role of TRPA1 as a target
      for neuroprotective approaches in retinal ischemia.

PMID- 27876488
TI  - Arthroscopic Subscapularis Augmentation of Bankart Repair in Chronic Anterior
      Shoulder Instability With Bone Loss Less Than 25% and Capsular Deficiency:
      Clinical Multicenter Study.
AB  - PURPOSE: To assess the short-term outcomes of the arthroscopic subscapularis
      augmentation (ASA) technique, consisting of a tenodesis of the upper third of the
      subscapularis tendon and a Bankart repair, and its effect on shoulder external
      rotation. METHODS: Patients selected for this study were involved in contact
      sports, with a history of traumatic recurrent shoulder dislocations and a minimum
      of 2-year follow-up. Inclusion criteria were patients with glenoid bone loss
      (GBL) ranging from 5% to 25%, anterior capsular deficiency, and Hill-Sachs lesion
      who underwent ASA technique. Exclusion criteria were GBL >25%, multidirectional
      instability, preexisting osteoarthritis, and overhead sports activities. Visual
      analog scale (VAS) scale for pain, Rowe score, and American Shoulder and Elbow
      Surgeons (ASES) scores were used to assess results. Loss of shoulder external
      rotation was measured with the arm at the side (ER1 position) or 90 degrees  in
      abduction (ER2 position). Analysis of variance and Fisher tests were used for
      data evaluation. Significance was established at P <= .05. RESULTS: One hundred
      ten patients (84 men and 26 women, mean age 27 years) were evaluated with a mean
      follow-up of 40.5 months (range: 24 to 65 months). In 98 patients, a Hill-Sachs
      lesion was observed and in 57 patients a capsular deficiency was present. Three
      patients (2.7%) had a traumatic redislocation. At final follow-up, the mean
      scores were as follows: VAS scale decreased from a mean of 3.5 to 0.5 (P = .015),
      Rowe score increased from 57.4 to 95.3 (P = .035), and ASES score increased from
      66.5 to 96.5 (P = .021). The mean deficit of external rotation was 8 degrees  +/-
      2.5 degrees  in the ER1 position and 4 degrees  +/- 1.5 degrees  in the ER2
      position. CONCLUSIONS: The ASA procedure has been shown to be effective in
      restoring joint stability in patients practicing sports, affected by chronic
      anterior shoulder instability associated with anterior GBL (<25%), capsular
      deficiency, and Hill-Sachs lesions, with mild restriction of external rotation.
      LEVEL OF EVIDENCE: Level IV, therapeutic case series.

PMID- 27876489
TI  - Morphologic Changes and Outcomes After Arthroscopic Acetabular Labral Repair
      Evaluated Using Postoperative Computed Tomography Arthrography.
AB  - PURPOSE: To investigate smaller sized labra after acetabular labral repair
      comparing preoperative and postoperative computed tomography arthrography (CTA)
      and to assess the correlation between the anatomic changes and clinical outcomes.
      METHODS: The design and protocol of this retrospective study were approved by the
      institutional review board of our hospital. The inclusion criteria included age
      older than 18 years and hip pain associated with mechanical symptoms. Patients
      with previous hip surgery, avascular necrosis, rheumatologic disorders, or
      advanced arthritis were excluded. All tears with femoroacetabular impingement
      were treated with bumpectomy or acetabuloplasty and repaired using arthroscopic
      suture anchors. We evaluated clinical outcomes using the modified Harris Hip
      Score (mHHS) and the morphologic changes and radiologic outcomes (labral retear
      and leakage of dye) using CTA at a minimum 2-year follow-up. The paired t test
      was performed to detect changes in labral height, labral width, and mHHS.
      RESULTS: Forty labral tears in 40 patients (mean age, 32.1 +/- 9.2 years)
      underwent labral repair, with femoroplasty in 20 hips and acetabuloplasty in 17
      hips, and no patients required capsular repair after capsulotomy. No leakage of
      contrast dye was detected during the follow-up CTA procedure. No labral retears
      were observed after labral refixation at the postoperative CTA evaluation.
      However, the mean width and height of the labrum changed from 8.1 mm and 4.9 mm,
      respectively, preoperatively to 6.7 mm and 4.4 mm, respectively, at the
      postoperative follow-up (decreasing by 19% and 11%, respectively; both P < .001).
      In addition, the mean mHHS for the 36 patients in the complete repair group
      improved from 61 +/- 16.0 to 90 +/- 9.6 (P = .01). Four hips showed incomplete
      repairs. CONCLUSIONS: Repaired labra are well maintained after capsulotomy based
      on follow-up CTA after arthroscopic labral repair. In addition, decreased height
      and width of the labra do not affect the clinical outcomes. LEVEL OF EVIDENCE:
      Level IV, therapeutic study (case series [no, or historical, control group]).

PMID- 27876491
TI  - Through rose-colored glasses: Bringing focus back to revascularization.

PMID- 27876492
TI  - Sutureless valve implantation: Every detail counts.

PMID- 27876490
TI  - Medial Open Wedge High Tibial Osteotomy for Varus Malunited Tibial Plateau
      Fractures.
AB  - PURPOSE: To analyze radiologic and functional outcomes of varus malunited tibial
      plateau fractures managed with medial open wedge high tibial osteotomy (MOHTO).
      METHODS: Eighteen patients with symptomatic varus malunited tibial plateau
      fractures with less than stage II arthritic changes managed from July 2009 to
      October 2013 were included. Patients with complex intra-articular step malunions
      and severe arthritic changes (stage III and IV) were excluded. Initially,
      diagnostic arthroscopy was performed followed by MOHTO stabilized with locking
      plate and tricortical autograft (n = 11, 61%) or a Puddu plate and allograft (n =
      7, 39%). Patients were evaluated radiologically for union, medial proximal tibial
      angle, and tibial slope angle, and functional assessment was performed with a
      knee outcome survey based on activities of daily living. RESULTS: The mean follow
      up duration was 41.7 +/- 12.1 months (range 25-61); all patients achieved
      radiologic union by a mean duration of 4.3 +/- 1.2 months (range 3-8). The mean
      medial proximal tibial angle improved from 75.3 degrees  +/- 3.7 degrees  (range
      70.5 degrees -85.2 degrees ) to a postoperative angle of 83.8 degrees  +/- 3.6
      degrees  (range 77.5 degrees -90.4 degrees ) (P < .001). In 12 patients, an
      abnormal mean anterior slope of -5.5 degrees  +/- 3.0 degrees  (range -1.1
      degrees  to -13 degrees ) was corrected to a postoperative posterior slope of 5.8
      degrees  +/- 4.4 degrees  (range -1.1 degrees  to 14.1 degrees ) (P < .001). In 6
      patients, a mean posterior slope of 17.4 degrees  +/- 10.5 degrees  (range 1.4
      degrees -33 degrees ) was corrected to a postoperative posterior slope of 14.08
      degrees  +/- 5.6 degrees  (range 7.4-21.3) (P = .214). The mean knee outcome
      survey scores preoperatively were 25% +/- 9.68% (range 8%-48%) and
      postoperatively were 85% +/- 11.18% (range -52% to 98%, P < .001). CONCLUSIONS:
      MOTHO for varus malunited tibial plateau fractures is safe and effective
      procedure that provides excellent functional outcomes, acceptable radiologic
      outcomes, and carries minimal complications. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 27876493
TI  - Not all that hibernates necessarily wakes up.

PMID- 27876494
TI  - Prevention of postoperative pulmonary complications and aggregation of marginal
      gains.

PMID- 27876495
TI  - Tough problem, creative solution.

PMID- 27876496
TI  - Peter Piper's pursuit of a perfect, parsimonious predictive model for prolonged
      air leaks.

PMID- 27876497
TI  - Hepatitis C virus inhibits CD4 T cell function via binding to Toll-like receptor
      7.
AB  - Toll-like receptor 7 (TLR7) is a ssRNA receptor that activates dendritic cells
      and macrophages upon ssRNA binding; however, little is known of its role in CD4+
      T cells. We show here that hepatitis C virus (HCV) induces a dose dependent
      inhibition of cytokine production and expression of activation markers in CD4 T
      cells, which were restored by a TLR7-specific antagonist. These findings indicate
      that HCV induces CD4 T cell impairment via TLR7 which may contribute to failure
      of virus eradication, casting doubts on the use of TLR7 agonists to boost innate
      immunity in chronic RNA virus infections.

PMID- 27876498
TI  - Associated lateral/medial knee instability and its relevant factors in anterior
      cruciate ligament-injured knees.
AB  - BACKGROUND: Associations of lateral/medial knee instability with anterior
      cruciate ligament (ACL) injury have not been thoroughly investigated. The
      purposes of this study were to investigate whether lateral/medial knee
      instability is associated with ACL injury, and to clarify relevant factors for
      lateral/medial knee instability in ACL-injured knees. METHODS: One hundred and
      nineteen patients with unilateral ACL-injured knees were included. Lateral/medial
      knee instability was assessed with varus/valgus stress X-ray examination for both
      injured and uninjured knees by measuring varus/valgus angle, lateral/medial joint
      opening, and lateral/medial joint opening index. Manual knee instability tests
      for ACL were evaluated to investigate associations between lateral/medial knee
      instability and anterior and/or rotational instabilities. Patients' backgrounds
      were evaluated to identify relevant factors for lateral/medial knee instability.
      Damage on the lateral collateral ligament (LCL) on MRI was also evaluated.
      RESULTS: All parameters regarding lateral knee instability in injured knees were
      significantly greater than in uninjured knees. There were significant
      correlations between lateral knee instability and the Lachman test as well as the
      pivot shift test. Patients with LCL damage had significantly greater lateral
      joint opening than those without LCL damage on MRI. Sensitivity of LCL damage on
      MRI to lateral joint opening was 100%, while its specificity was 36%. No other
      relevant factors were identified. In medial knee instability, there were also
      correlations between medial knee instability and the Lachman test/pivot shift
      test. However, the correlations were weak and other parameters were not
      significant. CONCLUSIONS: Lateral knee instability was greater in ACL-deficient
      knees than in uninjured knees. Lateral knee instability was associated with ACL
      related instabilities as well as LCL damage on MRI, whereas MRI had low
      specificity to lateral knee instability. On the other hand, the association of
      medial knee instability on ACL-related instability was less than that of lateral
      knee instability. LEVELS OF EVIDENCE: Level IV, case series with no comparison
      group.

PMID- 27876499
TI  - Prolonged hydrocephalus induced by intraventricular hemorrhage in rats is reduced
      by curcumin therapy.
AB  - Prolonged hydrocephalus is a major cause of severe disability and death of
      intraventricular hemorrhage (IVH) patients. However, the therapeutic options to
      minimize the detrimental effects of post-hemorrhagic hydrocephalus are limited.
      Curcumin has been reported to confer neuroprotective effects in numerous
      neurological diseases and injuries, but its role in IVH-induced hydrocephalus has
      not been determined. The aim of present study was to determine whether curcumin
      treatment ameliorates blood brain barrier (BBB) damage and reduces the incidence
      of post-hemorrhagic hydrocephalus in IVH rat model. Autologous blood
      intraventricular injection was used to establish the IVH model. Our results
      revealed that repeated intraperitoneal injection of curcumin ameliorated IVH
      induced learning and memory deficits as determined by Morris water maze and
      reduced the incidence of post-hemorrhagic hydrocephalus in a dose-dependent
      manner at 28 d post-IVH induction. Further, the increased BBB permeability and
      brain edema induced by IVH were significantly reduced by curcumin administration.
      In summary, these findings highlighted the important role of curcumin in
      improving neurological function deficits and protecting against BBB disruption
      via promoting the neurovascular unit restoration, and thus it reduced the
      severity of post-hemorrhagic hydrocephalus in the long term. It is believed that
      curcumin might prove to be an effective therapeutic component in prevent the post
      IVH hydrocephalus in the near future.

PMID- 27876501
TI  - Serum and urinary biomarkers that predict hepatorenal syndrome in patients with
      advanced cirrhosis.
AB  - BACKGROUND: Prediction of hepatorenal syndrome (HRS) remains difficult in
      advanced cirrhotic patients. AIMS: To evaluate use of serum and urine biomarkers
      to predict HRS. METHODS: We prospectively recruited Child's B or C cirrhotic
      patients with normal serum creatinine, and followed them for 12 weeks for the
      development of HRS. Serum Cystatin C (CysC), serum and urine Neutrophil
      Gelatinase-Associated Lipocalin (NGAL), serum and urine IL-18, serum N-acetyl
      beta-d glucosaminidase (NAG), urine kidney injury molecule-1 (KIM-1) and urine
      liver-type fatty acid binding protein (LFABP) were measured at recruitment
      (baseline), and their relationship with subsequent HRS investigated. RESULTS: 43
      patients were included. 12 (27.9%) developed HRS at 7.3+/-5.1 weeks from
      baseline. Logistic regression analysis showed that baseline urinary NGAL and
      urinary KIM-1 were significantly associated with the development of HRS (RR
      1.007, 95% CI 1.001-1.012, p=0.014; RR 1.973, 95% CI 1.002-3.886, p=0.049). The
      cut-off values for NGAL and KIM-1 to predict HRS were 18.72ng/mL and 1.499ng/mL
      respectively (AUCs 0.84, p=0.005; and 0.78, p=0.008). CONCLUSION: Urinary NGAL
      and KIM-1 could serve as biomarkers to predict HRS in advanced cirrhotic
      patients.

PMID- 27876500
TI  - Strong correlation between ASPM gene expression and HCV cirrhosis progression
      identified by co-expression analysis.
AB  - Hepatitis C virus (HCV) cirrhosis is at a high risk of hepatocellular carcinoma
      (HCC), and its progression is influenced by a complex network of gene
      interactions. A weighted gene co-expression network was constructed to identify
      gene modules associated with the seven-stage disease progression from HCV
      cirrhosis to HCV-related HCC (n=65). In the significant module (R2=0.86), a total
      of 25 network hub genes were identified, half of which were also hub nodes in the
      protein-protein interaction network of the module genes. In validation, most hub
      genes showed a moderate correlation with the disease progression, and only ASPM
      was highly correlated (R2=0.801). In the test set (n=63), ASPM was also more
      highly expressed in HCV cirrhosis with concomitant HCC than in those without HCC
      (P=0.0054). Gene set enrichment analysis (GSEA) demonstrated that the gene set of
      "regulation of protein amino acid phosphorylation" (n=20) was enriched in HCV
      cirrhosis samples with ASPM highly expressed (false discovery rate (FDR)=0.049).
      In gene ontology (GO) analysis, genes in the enriched set were associated with
      liver neoplasms and other neoplastic diseases. In conclusion, through co
      expression analysis, ASPM was identified and validated in association with the
      progression of HCV cirrhosis probably by regulating tumor-related
      phosphorylation.

PMID- 27876503
TI  - Cranio-caudal asymmetries in trabecular architecture reflect vertebral fracture
      patterns.
AB  - Clinically, vertebral fractures often occur in the upper lumbar spine and involve
      the superior endplate of a vertebra (which is immediately caudal to a disc).
      Knowledge that the cranial endplate of a disc is thicker and has greater bone
      mineral density (BMD) than the corresponding caudal endplate helps to explain
      this phenomenon. In this study, we investigated structural differences in
      vertebral trabeculae on either side of a lumbar disc to provide further insight
      into vertebral fracture risk. As the focus is trabecular difference within a
      spinal motion segment, we define cranial and caudal vertebral trabeculae relative
      to the disc. Ninety-two spinal motion segments from 46 cadaveric lumbar spines
      (males, mean age 50years, range 21-63years) were studied. Disc narrowing on
      radiography and spread of barium sulfate (BaSO4) on discography were measured to
      indicate disc degeneration. Micro-computed tomography (MUCT) images were obtained
      at a resolution of 82MUm for each vertebra and processed to include only
      vertebral trabeculae. Using image processing, the vertebral trabeculae were
      divided into superior and inferior halves, and then into central and peripheral
      regions which were approximately opposite to the disc pulposus and annulus, and
      further into anterior and posterior sub-regions. Microarchitecture measurements
      for each vertebral region were obtained to determine the differences between the
      cranial and caudal trabeculae (relative to disc) and their associations with age
      and disc degeneration within each spinal motion segment. Data from the upper
      (L1/2-L3/4) and lower (L4/5) lumbar segments were analyzed separately. In the
      upper lumbar region, the trabeculae cranial to a disc on average had 5.3% greater
      BMD and trabecular bone volume, 3.6% greater trabecular number, 9.7% greater
      connectivity density, and 3.7% less trabecular separation than the corresponding
      caudal trabeculae (P<0.05 for all). Similar trends were observed in peripheral,
      anterior and posterior regions, but not in central region. No structural
      difference was observed in the trabeculae of L4/5 segment. Structural asymmetries
      of vertebral trabeculae were not associated with age, disc degeneration, or disc
      narrowing. Vertebral trabecular parameters cranial to the disc were greater than
      caudally in the upper but not in the lower lumbar region. Findings further
      explain why vertebral fractures are more common in the upper lumbar region and
      more frequently involve the endplate caudal to a disc.

PMID- 27876502
TI  - Oldenlandia diffusa suppresses metastatic potential through inhibiting matrix
      metalloproteinase-9 and intercellular adhesion molecule-1 expression via p38 and
      ERK1/2 MAPK pathways and induces apoptosis in human breast cancer MCF-7 cells.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Oldenlandia diffusa (OD) has long been known as an
      apoptotic inducer in breast tumors in ethnomedicine. AIM OF THE STUDY: To
      scientifically confirm the anti-breast cancer effects of water, methanol (MeOH)
      and butanol (BuOH) extracts of O. diffusa on cell apoptosis, matrix
      metalloproteinases (MMPs), intercellular adhesion molecule (ICAM)-1 and
      intracellular signaling in MCF-7 breast cancer cells. MATERIALS AND METHODS: MeOH
      extracts (MOD) and BuOH extracts (BOD) were prepared and examined for their
      ability to inhibit phorbol myristate acetate (PMA)-induced matrix
      metalloproteinase (MMP)-9 and intercellular adhesion molecule (ICAM)-1
      expressions in MCF-7 human breast cancer cells. Additionally, transwell
      migration, invasion and transcriptional activity were assessed. Results of
      immunofluorescence confocal microscopy for translocation of NF-kappaB and p-ERK
      and p-p38 were also checked. Finally, apoptotic signals including processed
      caspase-8, caspase-7, poly ADP-ribose polymerase, Bax and Bcl-2 were examined.
      RESULTS: MOD and BOD specifically inhibited PMA-induced MMP-9 expression as well
      as invasive and migration potential via ICAM-1. The inhibitory activity was also
      based on the suppressed transcriptional activity in MCF-7 breast cancer cells.
      Results of immunofluorescence confocal microscopy showed that translocation of NF
      kappaB decreased upon BOD and MOD treatments, with a decreased level of p-ERK and
      p-p38 phosphorylation. In addition, treatment of MCF-7 cells with MOD and BOD
      activated apoptosis-linked proteins including enzymatically active forms of
      processed caspase-8, caspase-7 and poly ADP-ribose polymerase, together with
      increased expression of mitochondrial apoptotic protein, Bax and decreased
      expression of Bcl-2. CONCLUSION: The results indicate that OD as an anti
      metastatic agent suppresses the metastatic response by targeting p-ERK, p-38 and
      NF-kappaB, thus reducing the invasion capacity of MCF-7 breast cancer cells
      through inhibition of MMP-9 and ICAM-1 expression and plays an important role in
      the regulation of breast cancer cell apoptosis.

PMID- 27876504
TI  - Disease and Treatment Characteristics of Men Diagnosed With Metastatic Hormone
      Sensitive Prostate Cancer in Real Life: Analysis From a Commercial Claims
      Database.
AB  - BACKGROUND: Our understanding of the clinical characteristics and treatment
      patterns of men who present with newly diagnosed metastatic (M1) hormone
      sensitive prostate cancer is based mainly on clinical trial data. We sought to
      characterize the M1 population seen in routine clinical practice using a
      commercial claims database. PATIENTS AND METHODS: A US claims (2000-2013)
      database was used to identify patients with an index diagnosis of prostate
      cancer. M1 patients were identified by "International Classification of Diseases,
      9th revision, Clinical Modification" diagnosis codes of metastasis to bone,
      viscera, distant lymph node, and unspecified sites within 90 days of the prostate
      cancer diagnosis. Progression to castration-resistant prostate cancer was
      identified by exposure to >= 1 drugs approved for castration-resistant prostate
      cancer, including docetaxel, abiraterone acetate, cabazitaxel, enzalutamide,
      sipuleucel-T, mitoxantrone, estramustine, and radium-223. RESULTS: Among 326,907
      patients with an index prostate cancer diagnosis, 9199 (2.8%) had M1 disease,
      including 6955 with specified metastatic disease involving the bone (77%),
      viscera (38%), or lymph nodes (21%). The initial treatment of M1 disease was
      castration in 51%, localized therapy in 16%, prostate cancer drug only in 18%,
      and no treatment in 15%. The median time to first castration was 33 days.
      CONCLUSION: The proportion of men with prostate cancer who presented with M1
      disease was consistent with other observations. Only 51% of the patients were
      treated according to national guidelines recommending medical or surgical
      castration. The proportion with visceral involvement at presentation was greater
      than expected from the clinical trials data in the same population. Just as seen
      in other medical conditions, clinical trial data are not representative of real
      life patients seen in routine clinical practice.

PMID- 27876505
TI  - Squamous Cell Carcinoma of the Bladder: A SEER Database Analysis.
AB  - BACKGROUND: Scarce evidence exists regarding the management of squamous cell
      carcinoma (SCC) of the bladder. This study assessed the epidemiologic and
      treatment trends of SCC of the bladder. MATERIALS AND METHODS: Cases of SCC of
      the bladder, diagnosed from 1973 to 2013, were identified from the Surveillance,
      Epidemiology, and End Results (SEER) database. The incidence of SCC of the
      bladder with respect to time was assessed using the SEER United States population
      dataset. Relevant baseline characteristics were reported whenever available.
      Propensity-score matching for nonmetastatic patients receiving or not receiving
      radical surgery was then performed considering baseline characteristics. Survival
      analysis in the post-matching cohort was then evaluated using Kaplan-Meier
      analyses. RESULTS: A total of 5018 patients were identified. The median age group
      was 70 to 75 years. The incidence of bladder SCC has decreased during the period
      from 1973 to 2013 (P < .05). For the post-matching cohort, there was a
      statistically significant difference in cancer-specific and overall survival
      favoring the radical surgery group compared with radiation therapy or no
      treatment group (P < .0001 for both endpoints). The overall survival benefit was
      consistent regardless of the SEER stage (localized or regional). In multivariate
      analysis of the matched population, radical surgery, less advanced SEER summary
      stage, and age less than 70 years were associated with a better overall survival.
      CONCLUSION: This analysis suggests that for nonmetastatic SCC of the bladder,
      radical surgery achieves better outcomes compared with radiation therapy.
      Prospective trials to evaluate formal multimodality bladder-preserving protocols
      in this histologic subtype are needed.

PMID- 27876506
TI  - Fungal peptides from pneumonitis hypersensitivity etiologic agents are able to
      induce specific cellular immune response.
AB  - PURPOSE: Hypersensitivity pneumonitis (HP) is an immunoallergic disease due to
      chronic exposure to high quantities of different microorganisms such as
      Mycobacterium immunogenum (Mi), a mycobacterium, and Lichtheimia corymbifera
      (Lc), a filamentous fungus. It has recently been demonstrated that the protein
      DLDH (dihydrolipoyl dehydrogenase), is common to these microorganisms. This study
      aimed to investigate the immune potential of overlapping peptide pools covering
      the MiDLDH and LcDLDH. EXPERIMENTAL DESIGN: A selection of 34 peptides, from the
      MiDLDH and LcDLDH, able to interact with Major Histocompatibility Complex (MHC) 1
      and MHC 2, was obtained using three different epitope prediction websites. By
      means of ELISPOT assays, we compared the frequency of Interferon gamma (IFNgamma)
      secreting peripheral blood mononuclear cells (PBMC) after stimulation with
      overlapping peptide pools. Tests were performed using cells from 35 healthy blood
      donors. RESULTS: One peptide pool containing five peptides from MiDLDH and able
      to interact with MHC 2 induced a marked IFNgamma specific immune response (Pool
      F, p<0.001, Wilcoxon signed-rank test). CONCLUSION: This study demonstrated that
      peptides from microorganisms involved in HP were able to induce a high IFNgamma
      specific immune response after stimulation of PBMCs from healthy blood donors
      which could be useful to develop an effective prevention strategy.

PMID- 27876507
TI  - Exercise-induced cytokine changes in antigen stimulated whole-blood cultures
      compared to serum.
AB  - Strenuous exercise is followed by an elevation of many cytokines with
      inflammation regulating properties. Since most cytokines act at pico- or
      nanomolar concentrations many investigations failed to detect their
      concentrations in vivo. Hence, the aim of this study was to evaluate the
      significance of cytokine measurements (IL-1beta, TNF-alpha, IL-1ra, IL-6, CCL2
      and CXCL8) in a stimulated whole-blood culture (sWBC) compared to serum with
      respect to their exercise-induced kinetics and detection rates. 40 male
      volunteers (age: 25,5+/-4,3years, BMI: 24,00+/-2,24, VO2peak: 46,9+/
      4,1mL/kg*min) performed 60min of intensive bicycle exercise (80% VO2peak). Blood
      samples were taken before and for up to 24h after exercise. All cytokines were
      determined by a multiplex ELISA. There were weak to moderate correlations between
      cytokines in sWBC and serum. While exercise did not affect pro-inflammatory
      cytokines in serum, in sWBC only IL-1beta was increased 1.2-fold at 3h (p<0,05).
      All other cytokines increased both in sWBC and serum. The detection rate was
      superior in sWBC vs serum for most cytokines. Exercise-induced cytokine kinetics
      in sWBC do not reflect systemic changes. Both approaches provide a synergistic
      insight into inflammatory processes on the cytokine level.

PMID- 27876508
TI  - A behavioural and electrophysiological investigation of the effect of
      bilingualism on aging and cognitive control.
AB  - Given previous, but inconsistent, findings of language group differences on
      cognitive control tasks the current investigation examined whether such
      differences could be demonstrated in a sample of older bilingual adults.
      Monolingual and bilingual older adults performed three cognitive control tasks
      that have previously been used in the literature (i.e., Stroop, Simon and flanker
      tasks) while brain electrophysiological recordings took place. Both behavioural
      (response time and accuracy) and event-related brain potentials (ERPs; N2 and P3
      amplitude and latency) were compared across the two language groups. Processing
      differences between monolinguals and bilinguals were identified for each task,
      although the locus differed across the tasks. Language group differences were
      most clear in the Stroop task, with bilinguals showing superior performance both
      behaviourally and electrophysiologically. In contrast, for the Simon and flanker
      tasks there were electrophysiological differences indicating language group
      processing differences at the level of conflict monitoring (Simon task only) and
      stimulus categorization (Simon and flanker tasks), but no behavioural
      differences. These findings support suggestions that these three tasks that are
      often used to examine executive control processes show little convergent
      validity; however, there are clear language group differences for each task that
      are suggestive of superior performance for bilinguals, with behavioural
      differences emerging only in the linguistic Stroop task. Furthermore, it is clear
      that behavioural measures alone do not capture the language group effects in
      their entirety, and perhaps processing differences between language groups are
      more marked in a sample of older adults who are experiencing age-related
      cognitive changes than in younger adults who are at the peak of their cognitive
      capacity.

PMID- 27876510
TI  - Scene perception in age-related macular degeneration: Effect of spatial
      frequencies and contrast in residual vision.
AB  - Age-related macular degeneration (AMD) is characterized by a central vision loss.
      Here, we investigated the ability of AMD patients to process the spatial
      frequency content of scenes in their residual vision, depending of the luminance
      contrast level. AMD patients and normally-sighted elderly participants (controls)
      performed a categorization task involving large scenes (outdoors vs. indoors)
      filtered in low spatial frequencies (LSF), high spatial frequencies (HSF), and
      non-filtered scenes (NF). Luminance contrast of scenes was equalized between
      stimuli using a root-mean square (RMS) contrast normalization. In Experiment 1,
      we applied an RMS contrast of 0.1 (for luminance values between 0 and 1), a value
      situated between the mean contrast of LSF and HSF scenes in natural conditions.
      In Experiment 2, we applied an RMS contrast of 0.3, corresponding to the mean
      contrast of HSF scenes in natural conditions. In Experiment 3, we manipulated
      four levels of linearly-increasing RMS contrasts (0.05, 0.10, 0.15, and 0.20) for
      HSF scenes only. Compared to controls, AMD patients gave more non-responses in
      the categorization of HSF than NF or LSF scenes, irrespective of the contrast
      level of scenes. Performances improved as contrast increased in HSF scenes.
      Controls were not differentially affected by the spatial frequency content of
      scenes. Overall, results suggest that LSF processing is well preserved in AMD
      patients and allows efficient scene categorization in their parafoveal residual
      vision. The HSF processing deficit could be partially restored by enhancing
      luminance contrast.

PMID- 27876509
TI  - Connectivity-based constraints on category-specificity in the ventral object
      processing pathway.
AB  - Recent efforts to characterize visual object representations in the ventral
      object processing pathway in the human brain have led to contrasting proposals
      about the causes of neural specificity for different categories. Here we use
      multivariate techniques in a novel way to relate patterns of functional
      connectivity to patterns of stimulus preferences. Stimulus preferences were
      measured throughout the ventral stream to tools, animals, faces and places;
      separately, we measured the strength of functional connectivity of each voxel in
      the ventral stream to category-preferring regions outside the ventral stream.
      Multivariate analyses were then performed over ventral stream voxels, relating
      'category-preferences' to 'functional connectivity preferences'. We show that the
      relation of those two measures doubly dissociates 'tools' and 'places', within
      what is ostensibly 'place' selective cortex (parahippocampal gyrus).
      Specifically, in the parahippocampal gyrus, functional connectivity to the left
      inferior parietal lobule is selectively related to stimulus preferences for tools
      (and not places), while functional connectivity to retrosplenial cortex is
      selectively related to place preferences (and not tools preferences). These
      findings indicate that functional connectivity can be used to index
      representational content rather than just provide an understanding of 'which
      regions are talking to which regions'. We suggest that the connectivity of the
      brain is what drives category-specificity in the ventral stream, and that if this
      is correct, then understanding the connectivity of the ventral stream will be key
      to understanding the causes and function of category-specific neural
      organization.

PMID- 27876511
TI  - Modulation of microsaccades by spatial frequency during object categorization.
AB  - The organization of visual processing into a coarse-to-fine information
      processing based on the spatial frequency properties of the input forms an
      important facet of the object recognition process. During visual object
      categorization tasks, microsaccades occur frequently. One potential functional
      role of these eye movements is to resolve high spatial frequency information. To
      assess this hypothesis, we examined the rate, amplitude and speed of
      microsaccades in an object categorization task in which participants viewed
      object and non-object images and classified them as showing either natural
      objects, man-made objects or non-objects. Images were presented unfiltered
      (broadband; BB) or filtered to contain only low (LSF) or high spatial frequency
      (HSF) information. This allowed us to examine whether microsaccades were
      modulated independently by the presence of a high-level feature - the presence of
      an object - and by low-level stimulus characteristics - spatial frequency. We
      found a bimodal distribution of saccades based on their amplitude, with a split
      between smaller and larger microsaccades at 0.4 degrees  of visual angle. The
      rate of larger saccades (?0.4 degrees ) was higher for objects than non-objects,
      and higher for objects with high spatial frequency content (HSF and BB objects)
      than for LSF objects. No effects were observed for smaller microsaccades (<0.4
      degrees ). This is consistent with a role for larger microsaccades in resolving
      HSF information for object identification, and previous evidence that more
      microsaccades are directed towards informative image regions.

PMID- 27876512
TI  - Biomechanical constraints do not influence pantomime-grasping adherence to
      Weber's law: A reply to Utz et al. (2015).
AB  - Work by our group and others employed the within-participants variability in peak
      grip aperture as a 'just-noticeable-difference' (JND) in grasping. Notably, our
      group reported that grasping responses with decoupled spatial relations between
      stimulus and response (i.e., pantomime-grasping) produced JNDs that increased
      linearly with increasing target object size (i.e., adherence to Weber's law) and
      interpreted that result as law-based evidence of aperture shaping via relative
      visual information. In contrast, Utz et al. (2015) reported that pantomime
      grasping elicits an inverse JND/object size relationship and proposed that JNDs
      in grasping do not reflect the sensory properties of a target object but rather
      reflect range effects in the biomechanical limits of aperture opening (i.e., the
      biomechanical hypothesis). Thus, the biomechanical hypothesis asserts that small
      objects have a larger range of possible aperture values than larger objects due
      to reduced biomechanical freedom associated with the hand's effective range of
      motion. To test the biomechanical hypothesis we measured participants' maximal
      thumb and forefinger separation and custom-built target objects with widths that
      matched decile increments (i.e., 10 through 80%) of each participant's effective
      range of motion. Results showed that JNDs increased linearly with increasing
      target object size - a result incompatible with the biomechanical hypothesis.
      Instead, the JND/object size relationship observed here supports convergent
      evidence that pantomime-grasping is a perception-based task mediated via relative
      visual information.

PMID- 27876513
TI  - Are high lags of accommodation in myopic children due to motor deficits?
AB  - Children with a progressing myopia exhibit an abnormal pattern of high
      accommodative lags coupled with high accommodative convergence (AC/A) and high
      accommodative adaptation. This is not predicted by the current models of
      accommodation and vergence. Reduced accommodative plant gain and reduced
      sensitivity to blur have been suggested as potential causes for this abnormal
      behavior. These etiologies were tested by altering parameters (sensory,
      controller and plant gains) in the Simulink model of accommodation. Predictions
      were then compared to the static and dynamic blur accommodation (BA) measures
      taken using a Badal optical system on 12 children (6 emmetropes and 6 myopes, 8
      13years) and 6 adults (20-35years). Other critical parameters such as CA/C, AC/A,
      and accommodative adaptation were also measured. Usable BA responses were
      classified as either typical or atypical. Typical accommodation data confirmed
      the abnormal pattern of myopia along with an unchanged CA/C. Main sequence
      relationship remained invariant between myopic and nonmyopic children. An overall
      reduction was noted in the response dynamics such as peak velocity and
      acceleration with age. Neither a reduced plant gain nor reduced blur sensitivity
      could predict the abnormal accommodative behavior. A model adjustment reflecting
      a reduced accommodative sensory gain (ASG) coupled with an increased AC cross
      link gain and reduced vergence adaptive gain does predict the empirical findings.
      Empirical measures also showed a greater frequency of errors in accommodative
      response generation (atypical responses) in both myopic and control children
      compared to adults.

PMID- 27876514
TI  - An investigation of the spatial selectivity of the duration after-effect.
AB  - Adaptation to the duration of a visual stimulus causes the perceived duration of
      a subsequently presented stimulus with a slightly different duration to be skewed
      away from the adapted duration. This pattern of repulsion following adaptation is
      similar to that observed for other visual properties, such as orientation, and is
      considered evidence for the involvement of duration-selective mechanisms in
      duration encoding. Here, we investigated whether the encoding of duration - by
      duration-selective mechanisms - occurs early on in the visual processing
      hierarchy. To this end, we investigated the spatial specificity of the duration
      after-effect in two experiments. We measured the duration after-effect at adapter
      test distances ranging between 0 and 15 degrees  of visual angle and for within-
      and between-hemifield presentations. We replicated the duration after-effect: the
      test stimulus was perceived to have a longer duration following adaptation to a
      shorter duration, and a shorter duration following adaptation to a longer
      duration. Importantly, this duration after-effect occurred at all measured
      distances, with no evidence for a decrease in the magnitude of the after-effect
      at larger distances or across hemifields. This shows that adaptation to duration
      does not result from adaptation occurring early on in the visual processing
      hierarchy. Instead, it seems likely that duration information is a high-level
      stimulus property that is encoded later on in the visual processing hierarchy.

PMID- 27876515
TI  - Regenerative therapy for hypothyroidism: Mechanisms and possibilities.
AB  - The ability to derive functional thyroid follicular cells from embryonic stem
      cells (ESCs) or induced pluripotent stem cells (iPSCs) would provide potential
      therapeutic benefit for patients with congenital or post-surgical hypothyroidism.
      Furthermore, understanding the process by which thyroid follicular cells develop
      will also provide great insight into the key steps that regulate the development
      of other tissues derived from endoderm. Here we review the advances in our
      understanding of the process of thyroid follicular cell development including the
      creation of two models that have allowed for the rescue of hypothyroid mouse
      recipients through the transplantation of thyroid follicular cells derived from
      mouse ESCs. Rapid progress in the field suggests that the same success should be
      achievable with human ESCs or iPSCs in the near future. Additionally, the
      availability of ESC or iPSC-derived thyroid follicular cell models will provide
      ideal systems to explore how genetic mutations, drugs or illness impact thyroid
      function in a cell-autonomous fashion.

PMID- 27876518
TI  - An update on the role of proximal occlusion devices in carotid artery stenting.
AB  - Carotid artery stenting performed with distal embolic protection devices
      continues to show elevated rates of periprocedural stroke, in particular with
      high-risk groups. This article discusses the factors associated with protection
      devices that may contribute to this complication, performs a literature review to
      assess outcomes of carotid stenting with proximal occlusion devices, and assesses
      the role of proximal occlusion devices in the management of patients with carotid
      artery stenosis.

PMID- 27876516
TI  - Predictors of aortic growth in uncomplicated type B aortic dissection from the
      Acute Dissection Stent Grafting or Best Medical Treatment (ADSORB) database.
AB  - BACKGROUND: The high-risk patient cohort of uncomplicated type B aortic
      dissections (uTBADs) needs to be clarified. We compared uTBAD patients treated
      with best medical treatment (BMT), with and without aortic growth, from the Acute
      Dissection Stent Grafting or Best Medical Treatment (ADSORB) trial database.
      Furthermore, we looked for trends in outcome for aortic growth and remodeling
      after BMT and thoracic endovascular aortic repair (TEVAR) and BMT (TEVAR+BMT).
      METHODS: BMT patients with available baseline and a 1-year follow-up arterial
      computed tomography scan were identified. True lumen and false lumen diameter was
      assessed at baseline and at follow-up. Patients with false lumen growth (group I)
      and without false lumen growth (group II) were compared. Predictors of false
      lumen and total lumen (aortic) growth were identified. Lastly, BMT outcomes were
      compared with BMT+TEVAR for false lumen thrombosis and change in false lumen and
      total aortic diameter in four sections: 0 to 10 cm (A), 10 to 20 cm (B), 20 to 30
      cm (C), and 30 to 40 cm (D) from the left subclavian artery. RESULTS: The
      dissection was significantly longer in group I than in group II (43.2 +/- 4.9 cm
      vs 30.4 +/- 8.8 cm; P = .002). The number of vessels originating from the false
      lumen at baseline was identified as an independent predictor of false lumen
      growth (odds ratio, 22.1; 95% confidence interval, 1.01-481.5; P = .049).
      Increasing age was a negative predictor of total aortic diameter growth (odds
      ratio, 0.902; 95% confidence interval, 0.813-1.00; P = .0502). The proximal
      sections A and B showed complete thrombosis in 80.6% in the BMT+TEVAR group
      compared with 9.5% in the BMT group. In these sections, changes from patent to
      partial or partial to complete thrombosis were observed in 90.3% of the TEVAR+BMT
      group vs 31.0% in the BMT group. In sections C and D, the change in thrombosis
      was 74.1% for the TEVAR+BMT group vs 20.6% for the BMT group. The false lumen
      diameter increase at section C was larger in the BMT group. Total lumen diameter
      decreased in sections A and B in the TEVAR+BMT group compared with an increase in
      the BMT group (-4.8 mm vs +2.9 mm, and -1.5 mm vs +3.8 mm, respectively).
      Sections C and D showed minimal and comparable expansion in both treatment
      groups. CONCLUSIONS: The new imaging analysis of the ADSORB trial patients
      identified the number of vessels originating from the false lumen as an
      independent predictor of false lumen growth in uTBAD patients. Increasing age was
      a negative predictor of aortic growth. Our analysis may help to identify which
      uTBAD patients are at higher risk and should receive TEVAR or be monitored
      closely during follow-up.

PMID- 27876517
TI  - Clinical effects of single or double tibial artery revascularization in critical
      limb ischemia patients with tissue loss.
AB  - OBJECTIVE: The achievement of single vessel inflow to the wound is an acceptable
      end point of peripheral vascular intervention for patients with critical limb
      ischemia (CLI) with tissue loss. However, CLI patients often have multitibial
      artery lesions. We evaluated the clinical effects of single or double tibial
      artery revascularization for CLI patients. METHODS: This study was conducted
      retrospectively in a single center. Between April 2007 and January 2015, we
      treated 123 CLI patients (137 limbs) who had lesions in both the anterior tibial
      artery and the posterior tibial artery. Of these, single tibial artery (anterior
      or posterior tibial artery) revascularization was performed in 84 limbs (group S)
      and double tibial artery (both anterior and posterior tibial arteries)
      revascularization was performed in 53 limbs (group D). RESULTS: The wound healing
      rate was significantly higher (87% vs 79%; P = .003), the time to wound healing
      was shorter (median, 83 vs 142 days; P = .01), and the repeat peripheral vascular
      intervention rate was lower (15% vs 35%; P = .03) in group D than in group S. The
      wound healing rate was nearly similar between the 2 groups in patients with a low
      clinical stage as assessed by Society for Vascular Surgery Wound, Ischemia, and
      foot Infection (90% in group D vs 93% in group S; P = .20); however, the wound
      healing rate was significantly higher in group D in patients with a high clinical
      stage (85% vs 72%; P = .007). CONCLUSIONS: The achievement of double vessel
      inflows to the wound by double tibial artery revascularization positively affects
      wound healing, particularly in severe CLI patients.

PMID- 27876519
TI  - The effect of body mass index on major outcomes after vascular surgery.
AB  - OBJECTIVE: Obesity has been associated with an increased risk for cardiovascular
      morbidity and mortality, although pooled evidence in patients undergoing vascular
      surgery are lacking. The aim of this systematic review was to evaluate the effect
      of body mass index (BMI) on major postoperative outcomes in patients undergoing
      vascular surgery. METHODS: A systematic literature review conforming to
      established criteria to identify eligible articles published before May 2016 was
      conducted. Eligible studies evaluated major postoperative outcomes in vascular
      surgery patients of different BMI groups according to the weight classification
      of the National Institutes of Health criteria: underweight (UW), BMI <=18.5
      kg/m2; normal weight (NW), BMI of 18.6 to 24.9 kg/m2; overweight (OW), BMI of 25
      to 29.9 kg/m2; and obese (OB), BMI >=30 kg/m2. Major outcomes included 30-day
      mortality, cardiac complications, and respiratory complications. Secondary
      outcomes included wound and cerebrovascular complications, renal complications,
      deep venous thrombosis/pulmonary embolism, and other complications. RESULTS:
      Overall, eight retrospective studies were eligible including a total of 92,525
      vascular surgery patients (2223 UW patients, 29,727 NW patients, 34,517 OW
      patients, and 26,058 OB patients). Pooled data were as follows: mortality rate,
      2.5%; cardiac events, 2.1%; respiratory events, 8.6%; wound complications, 6.4%;
      cerebrovascular events, 6.4%; renal complications, 3.9%; other infections, 5.3%;
      deep venous thrombosis/pulmonary embolism, 1.2%; and other complications, 3.7%.
      Meta-analysis showed that OB patients were associated with lower mortality (odds
      ratio [OR], 0.64; 95% confidence interval [CI], 0.541-0.757; P < .0001), cardiac
      morbidity (OR, 0.81; 95% CI, 0.708-0.938; P = .004), and respiratory morbidity
      (OR, 0.87; 95% CI, 0.802-0.941; P = .0006) after vascular surgery compared with
      NW patients. However, OB patients were associated with a higher wound
      complication rate (OR, 2.39; 95% CI, 1.777-3.211; P < .0001) compared with NW
      patients. In contrast, UW patients were associated with a higher mortality (OR,
      1.71; 95% CI, 1.177-2.505; P = .005) and respiratory morbidity (OR, 1.84; 95% CI,
      1.554-2.166; P < .0001) compared with NW patients. CONCLUSIONS: The "obesity
      paradox" does exist in patients undergoing vascular surgery. This paradox refers
      not only to 30-day overall mortality but also to 30-day cardiac and respiratory
      complications. However, obesity seems to be associated with more wound
      complications. Surprisingly, UW patients are associated with higher mortality as
      well as respiratory events postoperatively.

PMID- 27876520
TI  - Explaining endograft shortening during endovascular repair of abdominal aortic
      aneurysms in severe aortoiliac tortuosity.
AB  - OBJECTIVE: During endovascular aneurysm repair (EVAR), severely tortuous
      aortoiliac anatomy can alter the deployment and conformability of the endograft.
      The accuracy of treatment length measurements is commonly recognized to be
      affected by severe tortuosity. However, the exact mechanism of the
      postintervention length discrepancy is poorly understood. The objective of this
      study was to determine the mechanism of how severe aortoiliac tortuosity
      influences the endograft and native aorta during EVAR and its impact on the
      distal sealing zone. METHODS: A prospectively collected vascular surgery database
      was retrospectively reviewed at a university-affiliated medical center to
      identify the study patients. Patients who underwent EVAR with the main body
      device deployed on the side of the severely tortuous iliac artery were selected.
      Severe aortoiliac tortuosity was defined as having either aortoiliac or common
      iliac angulation <90 degrees. RESULTS: A total of 469 patients between 2008 and
      2014 underwent EVAR using the Endurant endograft (Medtronic Cardiovascular, Santa
      Rosa, Calif). Severe aortoiliac tortuosity was observed in 36% of patients; 17
      patients were found to have the main body placed on the side of severe tortuosity
      without an extension limb. There was a significant shortening of the main body
      endograft length from 169 mm before EVAR to 147 mm after EVAR (P < .001). The
      treatment length of the main body, measured from the lowest renal artery to
      hypogastric artery, also significantly shortened from 179 mm to 170 mm (P <
      .001). There was a decrease in tortuosity at the most angulated portion of the
      aneurysm after EVAR, in which angulation changed from 86 degrees to 114 degrees
      (P < .001). There was no significant change in treatment length (P = .859) and
      angulation (P = .195) on the nontortuous side of the aneurysm. CONCLUSIONS: The
      study observed significant shortening of endografts and native aorta and iliac
      arteries in patients with severe aortoiliac tortuosity during EVAR. This
      shortening effect can have a negative impact on the distal sealing zone during
      EVAR. A longer main body or an extension limb should be considered when one is
      faced with severely tortuous aneurysms.

PMID- 27876522
TI  - Relative value unit-based compensation incentivization in an academic vascular
      practice improves productivity with no early adverse impact on quality.
AB  - OBJECTIVE: Given the increased pressure from governmental programs to restructure
      reimbursements to reflect quality metrics achieved by physicians, review of
      current reimbursement schemes is necessary to ensure sustainability of the
      physician's performance while maintaining and ultimately improving patient
      outcomes. This study reviewed the impact of reimbursement incentives on evidence
      based care outcomes within a vascular surgical program at an academic tertiary
      care center. METHODS: Data for patients with a confirmed 30-day follow-up for the
      vascular surgery subset of our institution's National Surgical Quality
      Improvement Program submission for the years 2013 and 2014 were reviewed. The
      outcomes reviewed included 30-day mortality, readmission, unplanned returns to
      the operating room, and all major morbidities. A comparison of both total charges
      and work relative value units (RVUs) generated was performed before and after
      changes were made from a salary-based to a productivity-based compensation model.
      P value analysis was used to determine if there were any statistically
      significant differences in patient outcomes between the two study years. RESULTS:
      No statistically significant difference in outcomes of the core measures studied
      was identified between the two periods. There was a trend toward a lower
      incidence of respiratory complications, largely driven by a lower incidence in
      pneumonia between 2013 and 2014. The vascular division had a net increase of 8.2%
      in total charges and 5.7% in work RVUs after the RVU-based incentivization
      program was instituted. CONCLUSIONS: Revenue-improving measures can improve
      sustainability of a vascular program without negatively affecting patient care as
      evidenced by the lack of difference in evidence-based core outcome measures in
      our study period. Further studies are needed to elucidate the long-term effects
      of incentivization programs on both patient care and program viability.

PMID- 27876521
TI  - Increased risk of renal dysfunction with percutaneous mechanical thrombectomy
      compared with catheter-directed thrombolysis.
AB  - OBJECTIVE: Percutaneous mechanical thrombectomy (PMT) is regularly used in the
      treatment of both venous and arterial thrombosis. Although there has been no
      formal report, PMT has been linked to cases of reversible postoperative acute
      kidney injury (AKI). The purpose of this study is to evaluate the risk of renal
      dysfunction in patients undergoing PMT vs catheter-directed thrombolysis (CDT)
      for treatment of an acute thrombus. METHODS: This study is a retrospective review
      of all patients in a single institution with a Current Procedural Terminology
      code for PMT or CDT from January 2009 through December 2014. Each patient was
      grouped into one of the four following procedural categories: PMT only, PMT with
      tissue plasminogen activator (tPA) pulse-spray, PMT with CDT, or CDT only.
      Preoperative and postoperative creatinine and glomerular filtration rate (GFR)
      values were obtained for each patient. The RIFLE (Risk, Injury, Failure, Loss,
      and End-stage renal disease) criteria were used to categorize the extent of renal
      dysfunction. chi2 analysis, one-way analysis of variance, and unpaired t-test
      were used to assess significance. RESULTS: A total of 227 patients were reviewed,
      of which 82 were excluded due to either existence of preoperative AKI, history of
      end-stage renal disease, or lack of clinical data. Of the remaining 145 patients,
      53 (37%) presented with arterial thrombosis (mean age, 62 years; 43% male) and 92
      (63%) presented with venous thrombosis (mean age, 48 years; 45% male). The
      incidence of renal dysfunction was highest in the PMT/tPA pulse group (21%),
      followed by the PMT group (20%) and the PMT/CDT group (14%). CDT was not
      associated with renal dysfunction. PMT (P = .046), and PMT/tPA pulse (P = .033)
      were associated with higher rates of renal dysfunction than the CDT controls. The
      average preoperative GFR for the 22 patients who developed AKI was 53.7 +/- 9.4
      mL/min/1.73 m2. The minimum postoperative GFR within 48 hours was an average of
      35 +/- 16 mL/min/1.73 m2. Stratified by the RIFLE criteria, 13 (9%) patients
      progressed to the risk category, 6 (4%) progressed to the injury category, and 3
      (2%) progressed to the failure category. None of the patients who developed renal
      dysfunction from PMT progressed to dialysis within the same admission period.
      CONCLUSIONS: The use of PMT as a treatment for vascular thrombosis is associated
      with renal dysfunction. Patients treated with PMT require postoperative vigilance
      and renal protective measures.

PMID- 27876523
TI  - Quality-of-life assessment as an outcomes measure in critical limb ischemia.
AB  - Critical limb ischemia (CLI) is a diagnosis plagued by significant comorbidity
      and high mortality rates. Overall survival remains poor in this population
      regardless of the procedure-related success as demonstrated by freedom from
      amputation, intervention, and patency. The literature has traditionally focused
      on physician-centered and lesion-centered outcomes with regards to limb salvage
      procedures, but there remains a relative paucity of studies of CLI patients
      describing patient-centered outcomes such as quality of life (QoL), independent
      living, and ambulation status. Review of the available literature indicates
      patients do not always experience significant gains in their QoL after limb
      salvage interventions, despite reasonable graft patency, amputation-free
      survival, and limb salvage rates. Further research is required using QoL tools in
      a measurable and clinically relevant fashion to guide optimal quality care that
      maximizes patient-centered outcomes.

PMID- 27876524
TI  - Lower extremity weakness is associated with elevated blood and cerebrospinal
      fluid glucose levels following multibranched endovascular aortic aneurysm repair.
AB  - OBJECTIVE: Hyperglycemia is associated with worsened clinical outcomes after
      central nervous system injury. The purpose of this study was to examine the
      association between lower extremity weakness (LEW) and the glucose levels of
      blood and cerebrospinal fluid (CSF) in patients undergoing multibranched
      endovascular aneurysm repair (MBEVAR) of thoracoabdominal and pararenal aortic
      aneurysms. METHODS: Blood and CSF samples were collected preoperatively,
      immediately after aneurysm repair, and on postoperative day 1 in 21 patients
      undergoing MBEVAR. Data on demographics, operative repair, complications, and
      outcomes were collected prospectively. RESULTS: There were 21 patients who
      underwent successful MBEVAR. Two patients had pre-existing paraplegia from prior
      open aortic surgery and were excluded from the current analysis. The mean age was
      73 +/- 8 years, and 15 of 19 (79%) were men. In the postoperative period, 7 of 19
      (37%) patients developed LEW. This was temporary in 5 of 19 (26%) patients and
      permanent in 2 of 19 (11%) patients. The LEW group was older than the non-LEW
      group (77 +/- 6 vs 70 +/- 9 years, respectively; P = .10), had a lower
      preoperative glomerular filtration rate (58.6 +/- 18.5 vs 71.4 +/- 23.5 mL/min
      per 1.73 m2; P = .24), and was more likely to be taking a statin (100% vs 67%,
      respectively; P = .13), but these did not reach statistical significance. There
      was no significant difference in the prevalence of diabetes mellitus,
      hypertension, coronary artery disease, lung disease, or peripheral artery disease
      between the LEW and non-LEW groups. There was also no difference in operative
      time, blood loss, contrast material volume, or fluoroscopy times between the two
      groups. Preoperative blood and CSF glucose levels were similar in those with and
      without LEW. During the postoperative period, glucose values in the blood and CSF
      were significantly higher in those patients who developed LEW compared with those
      who did not develop LEW. In all patients with LEW, the elevation in the blood or
      CSF glucose level preceded the development of LEW. In a multivariable logistic
      regression model, CSF glucose concentration on postoperative day 1 was
      significantly and independently associated with the development of LEW (odds
      ratio, 2.30 [1.03-5.14] per 10 mg/dL increase in CSF glucose; P = .04).
      CONCLUSIONS: Elevated blood glucose and CSF glucose levels are associated with
      postoperative LEW in patients undergoing MBEVAR. The protective effect of
      euglycemia deserves further study in patients at risk for spinal cord ischemia.

PMID- 27876525
TI  - IL-6 roles - Molecular pathway and clinical implication in pancreatic cancer - A
      systemic review.
AB  - Pancreatic cancer has attracted a great deal of attention owing to the poor
      outcome, increasing prevalence in the last years and delay diagnosis. Known as a
      complex disease, it involves genetic mutations, changes in tumour
      microenvironment and inflammatory component dominated by interleukin-6 and its
      activated pathways, like Janus Kinase-Signal Transducer and Activator of
      Translation3, Mitogen Activated Protein Kinase and Androgen receptor. The pro
      inflammatory cytokine, plays a central role in oncogenesis, cancer progression,
      invasiveness, microenvironment changes, treatment resistance, prognosis and
      associated co morbidities like cachexia and depression. Fulfilling these roles IL
      6 requires special attention to understand its complexity in PC development.

PMID- 27876527
TI  - Imagine.

PMID- 27876526
TI  - 1926-2016: 90 Years of listeriology.
AB  - ISOPOL - for "International Symposium on Problems of Listeria and Listeriosis" -
      meetings gather every three years since 1957 participants from all over the world
      and allow exchange and update on a wide array of topics concerning Listeria and
      listeriosis, ranging from epidemiology, diagnostic and typing methods, to
      genomics, post-genomics, fundamental microbiology, cell biology and pathogenesis.
      The XIXth ISOPOL meeting took place in Paris from June 14th to 17th, 2016 at
      Institut Pasteur. We provide here a report of the talks that were given during
      the meeting, which represents an up-to-date overview of ongoing research on this
      important pathogen and biological model.

PMID- 27876528
TI  - The impact of lens care solutions on corneal epithelial changes during daily
      silicone hydrogel contact lens wear as measured by in vivo confocal microscopy.
AB  - PURPOSE: To assess corneal epithelial microstructure via confocal microscopy and
      determine if cellular changes are associated with lens care solutions during
      daily wear of silicone hydrogel contact lenses. METHODS: Corneal in vivo confocal
      microscopy with the Nidek ConfoScan4 was performed at baseline and after 5 months
      of lotrafilcon A daily contact lens wear. Enrolled participants were randomized
      to use either a polyhexamethylene biguanide (PHMB) preserved multipurpose care
      solution (MPS) or a peroxide based solution system. Lens and storage case
      bioburden were assessed with aerobic culture methods. Univariate and
      multivariable analyses were done to evaluate the association between solution
      use, or solution-related clinical covariates, and morphologic differences (hyper
      reflectivity) in the superficial epithelial cells and epithelial basal cell
      density. RESULTS: Data on 139 participants were available for analysis of
      superficial epithelial cells while data on 92 participants were available for
      epithelial basal cell density. Five months after randomization to the solution
      groups, 33% of participants had visible hyper-reflective cells. More participants
      using MPS had >=1 hyper-reflective cells compared to peroxide users at 5 months
      (44% vs. 22%; p=0.006). Similarly at 5 months, more participants with solution
      induced corneal staining (SICS) had >=1 hyper-reflective cells compared to non
      SICS participants (57% vs. 29%; p=0.010). The adjusted odds ratios (ORs) for risk
      of presenting with hyper-reflective cells in MPS users or SICS participants was
      2.7 (95% CI; 1.27-5.65) and 3.4 (95% CI; 1.29-8.97), respectively. Basal cell
      density decreased by over 350 cells/mm2 over time (about 6%) in participants who
      had substantial bioburden on their lenses or in their storage case. CONCLUSION:
      The confocal microscope can detect epithelial cellular changes in vivo during
      contact lens wear. Hyper-reflective superficial epithelial cells are associated
      with a PHMB preserved solution and decreases in basal epithelial cell density may
      be associated with bacterial bioburden.

PMID- 27876529
TI  - Comparison of community and hospital pharmacists' attitudes and behaviors on
      medication error disclosure to the patient: A pilot study.
AB  - OBJECTIVES: To determine pharmacists' attitudes and behaviors on medication
      errors and their disclosure and to compare community and hospital pharmacists on
      such views. METHODS: An online questionnaire was developed from previous studies
      on physicians' disclosure of errors. Questionnaire items included demographics,
      environment, personal experiences, and attitudes on medication errors and the
      disclosure process. An invitation to participate along with the link to the
      questionnaire was electronically distributed to members of two Illinois pharmacy
      associations. A follow-up reminder was sent 4 weeks after the original message.
      Data were collected for 3 months, and statistical analyses were performed with
      the use of IBM SPSS version 22.0. RESULTS: The overall response rate was 23.3% (n
      = 422). The average employed respondent was a 51-year-old white woman with a BS
      Pharmacy degree working in a hospital pharmacy as a clinical staff member.
      Regardless of practice settings, pharmacist respondents agreed that medication
      errors were inevitable and that a disclosure process is necessary. Respondents
      from community and hospital settings were further analyzed to assess any
      differences. Community pharmacist respondents were more likely to agree that
      medication errors were inevitable and that pharmacists should address the
      patient's emotions when disclosing an error. Community pharmacist respondents
      were also more likely to agree that the health care professional most closely
      involved with the error should disclose the error to the patient and thought that
      it was the pharmacists' responsibility to disclose the error. Hospital pharmacist
      respondents were more likely to agree that it was important to include all
      details in a disclosure process and more likely to disagree on putting a
      "positive spin" on the event. CONCLUSION: Regardless of practice setting,
      responding pharmacists generally agreed that errors should be disclosed to
      patients. There were, however, significant differences in their attitudes and
      behaviors depending on their particular practice setting.

PMID- 27876531
TI  - Patient-centered quality of life measures after alloplastic temporomandibular
      joint replacement surgery.
AB  - The purpose of this study was to evaluate patient-reported outcome measures of
      quality of life (QoL) for patients with end-stage temporomandibular joint (TMJ)
      disease who have undergone TMJ prosthetic replacement. The records of 36 patients
      who had undergone alloplastic total joint replacement procedures were analyzed.
      Patients were treated using either TMJ Concepts or Biomet/Lorenz prosthetics.
      Patients were asked to complete a 12-item TMJ-S-QoL survey, which encompassed
      questions pertaining to pain, speech, chewing function, and various aspects of
      social life and mental health. The questions were answered on a 5-point scale.
      Data were analyzed using the Wilcoxon signed-rank test. Among the 36 patients
      (six male and 30 female), 18 responded to the survey. Markers of QoL after
      surgery were compared to the preoperative period. Significant improvements were
      reported for pain (94.4% of patients), chewing (83.3% of patients), speech (55.6%
      of patients), anxiety (72.2% of patients), activity (66.7% of patients),
      recreation (61.1% of patients), and mood (66.7% of patients) (all P<0.05). TMJ
      prosthetic replacement significantly enhanced QoL among patients suffering from
      chronic pain, limited range of motion, anxiety, impaired speech, and chewing due
      to end-stage TMJ disease in this sample of surgical patients.

PMID- 27876532
TI  - Efficacy of the C-terminal telopeptide test in predicting the development of
      bisphosphonate-related osteonecrosis of the jaw: a systematic review.
AB  - This systematic review evaluated the efficacy of the morning fasting serum C
      terminal telopeptide (CTX) test in predicting the development of bisphosphonate
      related osteonecrosis of the jaw (BRONJ). A comprehensive search of studies
      published up to March 2016, and listed in the PubMed/MEDLINE, Web of Science, and
      Cochrane Library databases, was performed in accordance with the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
      This review has been registered in the PROSPERO international prospective
      register of systematic reviews (CRD42016036717). The search identified 542
      publications; eight studies were finally deemed eligible for inclusion according
      to the study criteria. These studies included a total 1442 patients (mean age
      66.7 years). The most prescribed drug was alendronate, with osteoporosis being
      the most frequent indication for the prescription of bisphosphonates. Tooth
      extraction was the most common trigger for BRONJ. Of all patients evaluated after
      bisphosphonate treatment, only 24 (1.7%) developed BRONJ. All eight of the
      selected studies found that CTX levels were not predictive of the development of
      BRONJ. In conclusion, this systematic review indicates that the CTX test has no
      predictive value in determining the risk of osteonecrosis in patients taking
      bisphosphonates.

PMID- 27876530
TI  - Two adjacent phenylalanines in the NMDA receptor GluN2A subunit M3 domain
      interactively regulate alcohol sensitivity and ion channel gating.
AB  - The N-methyl-d-aspartate (NMDA) receptor is a key target of ethanol action in the
      central nervous system. Alcohol inhibition of NMDA receptor function involves
      small clusters of residues in the third and fourth membrane-associated (M)
      domains. Previous results from this laboratory have shown that two adjacent
      positions in the M3 domain, F636 and F637, can powerfully regulate alcohol
      sensitivity and ion channel gating. In this study, we report that these positions
      interact with one another in the regulation of both NMDA receptor gating and
      alcohol action. Using dual mutant cycle analysis, we detected interactions among
      various substitution mutants at these positions with respect to regulation of
      glutamate EC50, steady-state to peak current ratios (Iss:Ip), mean open time, and
      ethanol IC50. This interaction apparently involves a balancing of forces on the
      M3 helix, such that the disruption of function due to a substitution at one
      position can be reversed by a similar substitution at the other position. For
      example, tryptophan substitution at F636 or F637 increased or decreased channel
      mean open time, respectively, but tryptophan substitution at both positions did
      not alter open time. Interestingly, the effects of a number of mutations on
      receptor kinetics and ethanol sensitivity appeared to depend upon subtle
      structural differences, such as those between the isomeric amino acids leucine
      and isoleucine, as they could not be explained on the basis of sidechain
      molecular volume or hydrophilicity.

PMID- 27876533
TI  - Multiple single nucleotide polymorphisms in the first intron of the IL2RA gene
      affect transcription factor binding and enhancer activity.
AB  - IL2RA gene encodes the alpha subunit of a high-affinity receptor for interleukin
      2 which is expressed by several distinct populations of lymphocytes involved in
      autoimmune processes. A large number of polymorphic alleles of the IL2RA locus
      are associated with the development of various autoimmune diseases. With
      bioinformatics analysis we the dissected the first intron of the IL2RA gene and
      selected several single nucleotide polymorphisms (SNPs) that may influence the
      regulation of the IL2RA gene in cell types relevant to autoimmune pathology. We
      described five enhancers containing the selected SNPs that stimulated activity of
      the IL2RA promoter in a cell-type specific manner, and tested the effect of
      specific SNP alleles on activity of the respective enhancers (E1 to E5, labeled
      according to the distance to the promoter). The E4 enhancer with minor T variant
      of rs61839660 SNP demonstrated reduced activity due to disrupted binding of
      MEF2A/C transcription factors (TFs). Neither rs706778 nor rs706779 SNPs, both
      associated with a number of autoimmune diseases, had any effect on the activity
      of the enhancer E2. However, rare variants of several SNPs (rs139767239,
      rs115133228, rs12722502, rs12722635) genetically linked to either rs706778 and/or
      rs706779 significantly influenced the activity of E1, E3 and E5 enhancers,
      presumably by disrupting EBF1, GABPA and ELF1 binding sites.

PMID- 27876534
TI  - Transcranial magnetic stimulation modifies astrocytosis, cell density and
      lipopolysaccharide levels in experimental autoimmune encephalomyelitis.
AB  - AIMS: Experimental autoimmune encephalomyelitis (EAE) is considered a valid
      experimental model for multiple sclerosis, a chronic neuroinflammatory condition
      of the central nervous system. Additionally, some evidence has shown that some
      microbial products such as the bacterial lipopolysaccharide could lead to the
      activation of reactive immune cells, triggering neuroinflammation. Several
      studies have found that transcranial magnetic stimulation (TMS) may exert a
      neuroprotective effect. Therefore, we aimed to assess the effect of TMS on the
      neuroinflammation occurring in EAE. MATERIALS AND METHODS: A total of 44 male
      Dark Agouti rats were used. EAE induction was performed administering
      subcutaneously at the dorsal base of the tail a single dose of myelin
      oligodendrocyte glycoprotein. Clinical evaluation of motor symptoms was
      performed. Brain and spinal cord were collected and analyzed for nitric oxide,
      bacterial lipopolysaccharide and lipopolysaccharide-binding protein. We also
      carried out a histologic exam, which included an astrocyte immunostaining and
      Nissl staining for the assessment of brain cell density and pyknotic nuclei. KEY
      FINDINGS: TMS effectively ameliorated motor impairment secondary to EAE. This
      form of magnetic field was capable of decreasing the proliferation of astrocytes
      as a response to the autoimmune attack, reducing the content of nitric oxide,
      bacterial lipopolysaccharide and lipopolysaccharide-binding protein in central
      nervous system. Moreover, in treated animals, brain cell density was improved and
      the number of pyknotic nuclei was decreased. SIGNIFICANCE: Transcranial magnetic
      stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in
      EAE. These results suggest that TMS could be a promising treatment for
      neuroinflammatory conditions such as multiple sclerosis.

PMID- 27876537
TI  - Artificial Neural Networks approach to pharmacokinetic model selection in DCE-MRI
      studies.
AB  - PURPOSE: In pharmacokinetic analysis of Dynamic Contrast Enhanced MRI data, a
      descriptive physiological model should be selected properly out of a set of
      candidate models. Classical techniques suggested for this purpose suffer from
      issues like computation time and general fitting problems. This article proposes
      an approach based on Artificial Neural Networks (ANNs) for solving these
      problems. METHODS: A set of three physiologically and mathematically nested
      models generated from the Tofts model were assumed: Model I, II and III. These
      models cover three possible tissue types from normal to malignant. Using 21
      experimental arterial input functions and 12 levels of noise, a set of 27,216
      time traces were generated. ANN was validated and optimized by the k-fold cross
      validation technique. An experimental dataset of 20 patients with glioblastoma
      was applied to ANN and the results were compared to outputs of F-test using Dice
      index. RESULTS: Optimum neuronal architecture ([6:7:1]) and number of training
      epochs (50) of the ANN were determined. ANN correctly classified more than 99% of
      the dataset. Confusion matrices for both ANN and F-test results showed the
      superior performance of the ANN classifier. The average Dice index (over 20
      patients) indicated a 75% similarity between model selection maps of ANN and F
      test. CONCLUSIONS: ANN improves the model selection process by removing the need
      for time-consuming, problematic fitting algorithms; as well as the need for
      hypothesis testing.

PMID- 27876536
TI  - The protective effect of 1alpha, 25-dihydroxyvitamin d3 and metformin on liver in
      type 2 diabetic rats.
AB  - There is an accumulating evidence suggesting an immunomodulatory role of
      1alpha,25(OH)2D3. Altered 1alpha,25(OH)2D3 level may play a role in the
      development of T2DM and contribute to the pathogenesis of liver diseases. Our
      study was designed to study and compare the effect of metformin and
      1alpha,25(OH)2D3 supplementation on liver injury in type 2 diabetic rat. Sixty
      male Albino rats were divided into 5 groups; group 1: control rats. the remaining
      rats were fed high fat diet for 2 weeks and injected with streptozotocin (35mg/kg
      BW, i.p.) to induce T2DM and were divided into: group 2: untreated diabetic rats,
      group 3: diabetic rats treated by metformin (100mg/kgBW/d, orally), group 4:
      diabetic rats supplemented by 1alpha,25(OH)2D3 (0.5MUg/kg BW, i.p.) 3 times
      weekly and group 5: supplemented by both 1alpha,25(OH)2D3 and metformin. Eight
      weeks later, serum glucose and insulin levels were measured, HOMA IR was
      calculated, lipid profile, Ca2+, ALT and AST were estimated. Liver specimens were
      taken to investigate PPAR-alpha (regulator of lipid metabolism), NF-kappaB p65,
      caspase 3 and PCNA (proliferating cell nuclear antigen) and for histological
      examination. The liver enzymes were elevated in the diabetic rats and the
      histological results revealed an injurious effect of diabetes on the liver.
      1alpha,25(OH)2D3, metformin and both drugs treatment significantly improved liver
      enzymes as compared to the untreated rats. The improvement was associated with a
      significant improvement in the glycemic control, lipid profile and serum Ca2+
      with a significant reduction in NF-kappaB p65 and caspase 3 and increased PPAR
      alpha, and PCNA expression as compared to the untreated group. 1alpha,25(OH)2D3
      induced a slightly better effect as compared to metformin. Both agents together
      had a synergistic action and almost completely protected the liver. Histological
      results confirmed the biochemical findings. Our results showed a protective
      effect of 1alpha,25(OH)2D3 and metformin on liver in diabetic rats as indicated
      by an improvement of the level of the liver enzymes, decreased apoptosis and
      increased proliferation and this was confirmed histologically, with modulating
      NFkB and PPAR-alpha. Both agents together had a synergistic effect.

PMID- 27876538
TI  - Neutrophil to lymphocyte ratio and the hematoma volume and stroke severity in
      acute intracerebral hemorrhage patients.
AB  - BACKGROUND: Neutrophil to lymphocyte ratio (NLR) serves as a powerful
      inflammatory marker for predicting cardiovascular events. Here, we investigate
      whether admission NLR is associated with hematoma volume, stroke severity, and 3
      month outcomes in patients with acute intracerebral hemorrhage (ICH). METHODS:
      352 patients with acute ICH were prospectively identified in this study.
      Demographic characteristics, lifestyle risk factors, NIHSS score, hematoma
      volumes, and other clinical features were recorded for all participants. Patients
      was divided into quartiles based on the admission NLR levels (Q1: <2.78; Q2: 2.78
      4.08; Q3: 4.08-7.85; Q4: >=7.85). Multivariable linear regression models and
      logistic regression models were used to evaluate the association between NLR and
      hematoma volume, admission severity, or the outcomes after ICH. RESULTS: Median
      NIHSS scores for each quartile (Q1 to Q4) were 6.0, 6.0, 6.0, and 11.0 (P=.001),
      and median hematoma volumes were 9.5, 9.3, 9.1, and 15.0ml (P=.005),
      respectively. After adjusting the age, sex, and other potential risk factors, the
      patients in Q4 had higher NIHSS scores (P=.042) and larger hematoma volume
      (P=.014). After 3-month follow-up, 148 poor outcomes (mRS, 3-6) and 47 all-cause
      deaths were documented. There were more patients with poor outcomes in Q4 than
      Q1. However, compared with the patients in Q1, those in Q4 were not associated
      with poor outcomes (P-trend=0.379), and all-cause mortality (P-trend=0.843) after
      adjust for other risk factors. CONCLUSIONS: Higher admission NLR are associated
      with larger hematoma volume and more serious stroke, but not 3-month outcomes in
      patients with acute ICH.

PMID- 27876539
TI  - Antimicrobial resistance in urinary tract infections at a large urban ED: Factors
      contributing to empiric treatment failure.
AB  - OBJECTIVE: To calculate the emergency department (ED)-level Escherichia coli
      percentage of isolates susceptible to commonly used antibiotics and to determine
      the risk factors associated with inadequate empiric antibiotic therapy among
      patients treated for urinary tract infections (UTIs) in our ED. METHODS:
      Retrospective cohort study conducted at a large tertiary teaching hospital.
      Participants included patients older than 18years of age who had a urine culture
      with growth of >100,000 colonies of E. coli. Demographic and therapeutic choices
      associated with inadequate empiric antibiotic therapy were explored.
      Antimicrobial susceptibility pattern of E. coli isolates recovered from ED
      patients were calculated, and stratified by gender and age. RESULTS: A total of
      300 unique patients had E. coli bacteriuria during the study period. Among
      patients who received at least one dose of antibiotic in the ED, variables
      independently associated with an increased risk of inadequate empiric therapy
      were age (relative risk [RR] 1.016; 95% confidence interval [CI] 1.001-1.031;
      P=0.032), male gender (RR 2.507; 95% CI 1.470-4.486; P=0.001), and use of
      fluoroquinolones (RR 2.128; 95% CI 1.249-3.624 P=0.005). Sub-group analysis of
      patients discharged from the ED showed that definitive therapy with
      nitrofurantoin decreased the risk of inadequate empiric antibiotic therapy by 80%
      (RR 0.202; CI 0.065-0.638; P=0.006). ED-level antibiograms showed differences in
      antimicrobial susceptibility of E. coli by age and gender. CONCLUSIONS:
      Development of ED-level antimicrobial susceptibility data and consideration of
      patients' clinical characteristics can help better guide selection of empiric
      antibiotic therapy for the treatment of UTIs.

PMID- 27876535
TI  - 4-hydroxynonenal-mediated signaling and aging.
AB  - 4-Hydroxy-2-nonenal (HNE), one of the major alpha, beta-unsaturated aldehydes
      produced during lipid peroxidation, is a potent messenger in mediating signaling
      pathways. Lipid peroxidation and HNE production appear to increase with aging.
      Although the cause and effect relation remains arguable, aging is associated with
      significant changes in diverse signaling events, characterized by enhanced or
      diminished responses of specific signaling pathways. In this review we will
      discuss how HNE may contribute to aging-related alterations of signaling
      pathways.

PMID- 27876540
TI  - Laryngotracheal separation following blunt neck trauma.

PMID- 27876541
TI  - Diagnostic performance of a biomarker panel as a negative predictor for acute
      appendicitis in adult ED patients with abdominal pain.
AB  - OBJECTIVES: Evaluate the diagnostic accuracy of the APPY1TM biomarker panel,
      previously described for use in pediatric patients, for identifying adult ED
      patients with abdominal pain who are at low risk of acute appendicitis. METHODS:
      This study prospectively enrolled subjects >18years of age presenting to seven
      U.S. emergency departments with <72hours of abdominal pain suggesting possible
      acute appendicitis. The APPY1 panel was performed on blood samples drawn from
      each patient at the time of initial evaluation and results were correlated with
      the final diagnosis either positive or negative for acute appendicitis. RESULTS:
      431 patients were enrolled with 422 completing all aspects of the study. The
      APPY1 biomarker panel exhibited a sensitivity of 97.5% (95% CI, 91.3-99.3%), a
      negative predictive value of 98.4% (95% CI, 94.4-99.6%), a negative likelihood
      ratio of 0.07 (95% CI, 0.02-0.27), with a specificity of 36.5% (95% CI, 31.6
      41.8%) for acute appendicitis. The panel correctly identified 125 of 342 (36.6%)
      patients who did not have appendicitis with 2 (2.5%) false negatives. The CT
      utilization rate in this population was 72.7% (307/422). Of 307 CT scans, 232
      were done for patients who did not have appendicitis and 79 (34%) of these
      patients were correctly identified as negative with "low risk" biomarker panel
      results, representing 26% (79/307) of all CT scans performed. CONCLUSION: This
      biomarker panel exhibited high sensitivity and negative predictive value for
      acute appendicitis in this prospective adult cohort, thereby potentially reducing
      the dependence on CT for the evaluation of possible acute appendicitis.

PMID- 27876542
TI  - Successful percutaneous coronary intervention of total chronic occlusion of the
      left main coronary artery: A feasible option?

PMID- 27876544
TI  - Follow up of surgically-assisted rapid maxillary expansion after 6.5 years:
      skeletal and dental effects.
AB  - Surgically-assisted rapid maxillary expansion (SARME) is a technique used to
      widen the maxilla, and we present the results of our long-term follow up (6.5
      years). Seventeen patients who had been treated with SARME and prospectively
      followed were invited for long-term follow up using dental casts and
      posteroanterior cephalograms. The following measurements were made on the dental
      casts: transverse distances at canine, premolar, and molar level, length of the
      arch, and width and depth of the palate at premolar and molar level. The distance
      between the left and right nasal bases and the widening of the inferior maxilla
      were measured on the posteroanterior cephalograms. Boneborne and toothborne
      distractors were used in 8 and 9 patients, respectively. In the study of dental
      casts, there was a significant increase in transverse width in the canine
      (P<0.001), premolar (P<0.001) and molar (P=0,001) and these remained stable in
      the long term. The arch length did not increase significantly, but the palatal
      width increased significantly in the premolar (P<0.001) and molar (P=0.001)
      regions. No effect was seen in palatal depth. On the posteroanterior cephalograms
      the width of the inferior part of the maxilla was increased, but not
      significantly so. There were no significant changes at the nasal base. We
      conclude that SARME is a predictable technique to widen the maxilla in the long
      term.

PMID- 27876545
TI  - Submental island flap reconstruction in oral cavity cancer patients with level I
      lymph node metastasis.
AB  - The submental island flap is useful as an alternative to microvascular free
      tissue transfer for the reconstruction of defects after resection of oral cancer
      because it is simple to harvest, reliable, and is associated with good oral
      function and low morbidity. However, because cancer of the oral cavity carries a
      risk of level I nodal metastases, the oncological safety of the flap remains
      controversial. Between April 2012 and September 2016, we studied patients with
      squamous cell carcinoma of the oral cavity who had surgical resection with
      submental island flap reconstruction for viability of the flap, signs of
      recurrence, and complications. Thirty-five patients (22 men and 13 women) were
      enrolled in the study and the mean (range) duration of follow-up was 23 (11-48)
      months. Six patients had local recurrences of their tumours, none of which was
      considered to be related to the flap. No flap was lost completely, but there were
      10 cases of partial skin loss that healed with conservative management. There
      were no orocutaneous fistulas, haematomas, or marginal mandibular nerve palsies.
      We conclude that the submental island flap can be used safely in selected
      patients with level I lymph node metastases when the flap has been harvested
      meticulously.

PMID- 27876546
TI  - Occupational exposure to bodily fluids in oral and maxillofacial surgery: an
      evaluation of reporting practices and attitudes among staff at a major teaching
      hospital in the UK.
AB  - Our aim was to evaluate experience, practice, and beliefs about reporting of
      occupational exposures to blood and other body fluids among a sample of 88
      healthcare providers working in oral and maxillofacial surgery at Sheffield
      Teaching Hospitals. We used a cross-sectional survey to evaluate awareness of the
      Trust's policy for reporting occupational exposure, recent incidence of exposure,
      and current reporting practices. Beliefs were measured using questions derived
      from the theory of planned behaviour. Fifty-five people responded, 14 of whom had
      been exposed to bodily fluids in the previous 12 months. Of those, 10 did not
      report it. Fifty-three respondents were certain that the Trust had a protocol in
      place for reporting sharps injuries to staff. Most (n=51) said the Trust had a
      protocol for reporting mucocutaneous exposure to blood. Respondents placed equal
      importance on reporting exposures that affected both themselves and patients, but
      intention to report exposure of patients was significantly higher than for
      themselves (z score -3.18, p<0.0001). We conclude that OMFS healthcare workers
      generally think that occupational exposures should be reported, but there are
      shortcomings in practice.

PMID- 27876543
TI  - In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in
      adolescent boys: The CHAMACOS study.
AB  - Dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ether (PBDE) flame
      retardants, and polychlorinated biphenyls (PCBs) are believed to be endocrine
      disrupting chemicals (EDCs) in humans and animals. The purpose of this study is
      to examine the relationship of in utero and childhood exposure to these purported
      EDCs and reproductive hormones in adolescent boys who participated in CHAMACOS,
      an ongoing birth cohort in California's Salinas Valley. We measured o,p'- and
      p,p'-DDT, p,p'-DDE, PBDEs and PCBs in serum collected from mothers during
      pregnancy or at delivery and from their sons at 9 years. We measured
      concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH),
      and total testosterone (T) from 234 of their sons at 12 years. In adjusted
      models, we found that a 10-fold increase in maternal prenatal serum
      concentrations of BDE-153 was associated with a 22.2% increase (95% CI: 1.0,
      47.9) in FSH, a 96.6% increase (95% CI: 35.7, 184.7) in LH, and a 92.4% increase
      (95% CI: 20.9, 206.2) increase in T. Similarly, BDE-100 concentrations were
      associated with increases in boys' LH levels. A 10-fold increase in total
      prenatal SigmaPCBs was associated with a 64.5% increase (95% CI: 8.6, 149.0) in
      FSH, primarily driven by non- dioxin-like congeners. Boys' hormone levels were
      only marginally associated with prenatal DDT or DDE in primary models, but when
      boys' Tanner stage at age 12 was added to models, prenatal maternal DDT levels
      were associated with decreases in LH (adjusted percent change per 10-fold
      increase=-18.5%, 95% CI: -29.8, -5.4) and T (percent change=-18.2%, 95% CI: 
      30.2, -4.2) and DDE with LH (percent change=-18.3%, 95% CI: -32.9, -0.6).
      Exposures measured in the children's serum at 9 years also showed associations
      between BDE-153 and SigmaPCBs. However, there is evidence that these associations
      appear to be mediated by child BMI. This study suggests associations on male
      hormones of 12year old boys related to exposure to certain EDC exposure
      prenatally. The implications on future reproductive function in puberty and
      adulthood should be determined.

PMID- 27876547
TI  - Scheduling terminology for oral and maxillofacial surgery. Are we speaking a
      universal language?
AB  - Use of a universal vocabulary to assist with the scheduling of operations has
      been shown to considerably reduce delays and improve the use of theatre
      resources. Within the UK the National Confidential Enquiry into Patient Outcome
      and Death (NCEPOD) has established a classification to assist with the triage of
      both emergency and non-emergency operating lists. We completed a survey to assess
      the uptake and understanding of this classification when scheduling maxillofacial
      operations. From a list of eight scheduling terms, respondents had to choose one
      each for 20 different clinical situations (that represented equally) immediate,
      urgent, expedited, and elective operations as defined by them. A total of 50
      surveys were collated. Only 65% of answers selected represented NCPOD terms. 25%
      of answers represented a term higher and 18% a term lower, on the scale of
      intervention for the same category of situation. Current NCEPOD terms do not seem
      to be used universally and are poorly understood. Considerable variation in
      terminology exists when scheduling maxillofacial operations.

PMID- 27876548
TI  - The Effects of Replication Stress on S Phase Histone Management and Epigenetic
      Memory.
AB  - When a cell divides, it must not only accurately duplicate its genome but also
      recapitulate its programme of gene expression. A significant body of evidence
      suggests that an important fraction of the information specifying the
      transcriptional programme of vertebrate cells is carried epigenetically by post
      translational modifications of histone proteins. For such a system to operate,
      propagation of key histone marks must be coupled to replication such that they
      remain correctly associated with the underlying DNA sequence, despite the huge
      disruption to chromatin structure generated by unwinding the parental DNA
      strands. Focusing on vertebrate cells but drawing on experimental evidence from a
      wide range of systems, we will examine the evidence that histone mark propagation
      through replication contributes to transcriptional stability. We then discuss the
      emerging molecular mechanisms that ensure that histone recycling is tightly
      coupled to DNA replication, focusing on how parental histone proteins are
      chaperoned around the replication fork, and the strategies that ensure that this
      process is not disrupted by impediments to replication.

PMID- 27876549
TI  - Nitrogen-fixing bacteria and arbuscular mycorrhizal fungi in Piptadenia
      gonoacantha (Mart.) Macbr.
AB  - The family Leguminosae comprises approximately 20,000 species that mostly form
      symbioses with arbuscular mycorrhizal fungi (AMF) and nitrogen-fixing bacteria
      (NFB). This study is aimed at investigating and confirming the dependence on
      nodulation and biological nitrogen fixation in the specie Piptadenia gonoacantha
      (Mart.) Macbr., which belongs to the Piptadenia group. Two consecutive
      experiments were performed in a greenhouse. The experiments were fully randomized
      with six replicates and a factorial scheme. For the treatments, the two AMF
      species and three NFB strains were combined to nodulate P. gonoacantha in
      addition to the control treatments. The results indicate this species' capacity
      for nodulation without the AMF; however, the AMF+NFB combinations yielded a
      considerable gain in P. gonoacantha shoot weight compared with the treatments
      that only included inoculating with bacteria or AMF. The results also confirm
      that the treatment effects among the AMF+NFB combinations produced different
      shoot dry weight/root dry weight ratios. We conclude that AMF is not necessary
      for nodulation and that this dependence improves species development because
      plant growth increases upon co-inoculation.

PMID- 27876550
TI  - Eukaryotic Phosphate Homeostasis: The Inositol Pyrophosphate Perspective.
AB  - Phosphate, as a cellular energy currency, essentially drives most biochemical
      reactions defining living organisms, and thus its homeostasis must be tightly
      regulated. Investigation into the role of inositol pyrophosphates (PP-IPs) has
      provided a novel perspective on the regulation of phosphate homeostasis. Recent
      data suggest that metabolic and signaling interplay between PP-IPs, ATP, and
      inorganic polyphosphate (polyP) influences and is influenced by cellular
      phosphate homeostasis. Different studies have demonstrated that the SPX protein
      domain is a key component of proteins involved in phosphate metabolism. How PP
      IPs control some aspects of phosphate homeostasis has become clearer with the
      recently acquired crystal structures of SPX domains. We review here recent
      studies on eukaryote phosphate homeostasis and provide insights into future
      research.

PMID- 27876551
TI  - Stressed and Inflamed, Can GSK3 Be Blamed?
AB  - Psychological stress has a pervasive influence on our lives. In many cases
      adapting to stress strengthens organisms, but chronic or severe stress is usually
      harmful. One surprising outcome of psychological stress is the activation of an
      inflammatory response that resembles inflammation caused by infection or trauma.
      Excessive psychological stress and the consequential inflammation in the brain
      can increase susceptibility to psychiatric diseases, such as depression, and
      impair learning and memory, including in some patients with cognitive deficits.
      An emerging target to control detrimental outcomes of stress and inflammation is
      glycogen synthase kinase-3 (GSK3). GSK3 promotes inflammation, partly by
      regulating key transcription factors in the inflammation signaling pathway, and
      GSK3 can impair learning by promoting inflammation and by inhibiting long-term
      potentiation (LTP). Drugs inhibiting GSK3 may prove beneficial for controlling
      mood and cognitive impairments caused by excessive stress and the associated
      neuroinflammation.

PMID- 27876553
TI  - Why devote an entire issue to the topic of how nutrients in one-carbon metabolism
      play roles in modern medicine?

PMID- 27876554
TI  - Interaction between excess folate and low vitamin B12 status.
AB  - Current epidemiological evidence suggests that an imbalance of high folate status
      and low vitamin B12 status is associated with negative health outcomes in older
      adults and children. Such an imbalance during pregnancy also predisposes women to
      diabetes and their offspring to insulin resistance and adiposity and low
      birthweight. In older adults, vitamin B12 status can remain low despite adequate
      intake due to age-related decline in vitamin B12 absorption. Pregnant women are
      exposed to folic acid at varying doses depending on the prenatal care prescribed
      in different countries. This review summarizes the current knowledge on the
      interaction between folate and vitamin B12 and the associated health outcomes.

PMID- 27876555
TI  - One-carbon metabolism and epigenetics.
AB  - The function of one-carbon metabolism is that of regulating the provision of
      methyl groups for biological methylation reactions including that of DNA and
      histone proteins. Methylation at specific sites into the DNA sequence and at
      histone tails are among the major epigenetic feature of mammalian genome for the
      regulation of gene expression. The enzymes within one-carbon metabolism are
      dependent from a number of vitamins or nutrients that serve either as co-factors
      or methyl acceptors or donors among which folate, vitamin B12, vitamin B6,
      betaine, choline and methionine have a major role. Several evidences show that
      there is a strict inter-relationship between one-carbon metabolism nutrients and
      epigenetic phenomena. Epigenetics is closely involved in gene transcriptional
      regulation through modifications super-imposed to the nucleotide sequence of DNA,
      such as DNA methylation, through chromatin remodeling systems that involves post
      translational modifications of histones or through non-coding RNAs-based
      mechanisms. The epigenetic features of the genome are potentially modifiable by
      the action of several environmental factors among which nutrients cover a special
      place and interest considering their potential of influencing regulatory pathways
      at a molecular level by specific nutritional intervention and eventually
      influence disease prevention and outcomes. The present review will focus on the
      link between one-carbon nutrients and epigenetic phenomena based on the current
      knowledge from findings in cell culture, animal models and human studies.

PMID- 27876556
TI  - Homocysteine and disease: Causal associations or epiphenomenons?
AB  - Nutritional and genetic deficiencies of folate and vitamin B12 lead to elevation
      of cellular homocysteine (Hcy), which translates in increased plasma Hcy. The
      sources and role of elevated plasma Hcy in pathology continues to be a subject of
      intense scientific debate. Whether a cause, mediator or marker, little is known
      about the molecular mechanisms and interactions of Hcy with cellular processes
      that lead to disease. The use of folic acid reduces the incidence of neural tube
      defects, but the effect of Hcy-lowering interventions with folic acid in
      cardiovascular disease and cognitive impairment remains controversial. The fact
      that levels of Hcy in plasma do not always reflect cellular status of this amino
      acid may account for the substantial gaps that exist between epidemiological,
      intervention and basic research studies. Understanding whether plasma Hcy is a
      mechanistic player or an epiphenomenon in pathogenesis requires further
      investigation, and this research is essential to improve the assessment and
      potential treatment of hyperhomocysteinemias.

PMID- 27876552
TI  - Long-term altered immune responses following fetal priming in a non-human primate
      model of maternal immune activation.
AB  - Infection during pregnancy can lead to activation of the maternal immune system
      and has been associated with an increased risk of having an offspring later
      diagnosed with a neurodevelopmental disorders (NDD) such as autism spectrum
      disorder (ASD) or schizophrenia (SZ). Most maternal immune activation (MIA)
      studies to date have been in rodents and usually involve the use of
      lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C). However,
      since NDD are based on behavioral changes, a model of MIA in non-human primates
      could potentially provide data that helps illuminate complex behavioral and
      immune outputs in human NDD. In this study twenty-one pregnant rhesus macaques
      were either given three injections over 72 hours of poly I:C-LC, a double
      stranded RNA analog (viral mimic), or saline as a control. Injections were given
      near the end of the first trimester or near the end of the second trimester to
      determine if there were differences in immune output due to the timing of MIA.An
      additional three non-treated animals were used as controls. The offspring were
      followed until 4 years of age, with blood collected at the end of their first
      (year 1) and fourth (year 4) years to assess dynamic cellular immune function.
      Induced responses from peripheral immune cells were measured using multiplex
      assays.At one year of age, MIA exposed offspring displayed elevated production of
      innate inflammatory cytokines including: interleukin (IL)-1beta, IL-6, IL-12p40,
      and tumor necrosis factor (TNF)alpha at baseline and following stimulation. At
      four years of age, the MIA exposed offspring continued to display elevated IL
      1beta, and there was also a pattern of an increased production of T-cell helper
      type (TH)-2 cytokines, IL-4 and IL-13. Throughout this time period, the offspring
      of MIA treated dams exhibited altered behavioral phenotypes including increased
      stereotyped behaviors. During the first two years, stereotyped behaviors were
      associated with innate cytokine production. Self-directed behaviors were
      associated with TH2 cytokine production at year 4. Data from this study suggests
      long-term behavioral and immune activation was present in offspring following
      MIA. This novel non-human primate model of MIA may provide a relevant clinically
      translational model to help further elucidate the role between immune dysfunction
      and complex behavioral outputs following MIA.

PMID- 27876558
TI  - Prevalidation trial for a novel in vitro eye irritation test using the
      reconstructed human cornea-like epithelial model, MCTT HCETM.
AB  - Here, we report the results of a prevalidation trial for an in vitro eye
      irritation test (EIT) using the reconstructed human cornea-like epithelium, MCTT
      HCETM. The optimal cutoff to determine irritation in the prediction model was
      established at 35% with the receiver operation characteristics(ROC) curve for 126
      substances. Within-lab(WL) and between-lab(BL) reproducibility was tested for 20
      reference substances by 3 participating laboratories. Viability data described by
      mean+/-SD or +/-1/2 difference between duplicate wells, and scatter plots,
      demonstrated the WL/BL consistency. WL/BL concordance with the binary decision,
      whether non-irritant or irritant was estimated to be 85-95% and 95%,
      respectively. WL/BL reproducibility of viability data was further supported by a
      strong correlation(ICC, r>0.9). WL/BL agreement of binary decisions was also
      examined by Fleiss' Kappa statistics, which showed a strong level of agreement
      (>0.78), nevertheless weaker than the reproducibility of the viability. The EIT
      with MCTT HCETM exhibited a sensitivity of 82.2% (60/73), a specificity of 81.1%
      (43/53), and an accuracy of 81.8% (103/126) for 126 reference substances (for
      liquids; a sensitivity of 100% (47/47), a specificity of 70.6% (24/34), and an
      accuracy of 87.7% (71/81), and for solids, a sensitivity of 50% (13/26), a
      specificity of 100% (19/19), and an accuracy of 71.1% (32/45), suggesting that
      the accuracy is satisfactory but the sensitivity needs improvement, which shall
      be addressed through correcting the poor sensitivity for solid substances in
      future full validation trials.

PMID- 27876559
TI  - Non-dominant hand quicker to insert peripheral venous catheters under echographic
      guidance: A randomised trial.
AB  - BACKGROUND: Ultrasound guidance for venous catheter placement requires the use of
      both hands. An accurate and stable ultrasound image is fundamental for obtaining
      good quality images, consequently permitting accurate needle placement. We
      hypothesized that the dominant hand could be used to perform echography, leaving
      the non-dominant hand available for peripheral venous catheter (PVC) insertion.
      METHODS: Prospective, open-label, randomized, crossover study. Group 1 inserted
      the PVC with the dominant hand, and held the probe with the non-dominant hand in
      a first series of 20 insertions, and vice versa in a second series of 20
      insertions performed 11days later. Group 2 punctured with the non-dominant hand
      in Series 1 and vice versa in series 2. The study population comprised female
      student nurses (aged 20-30years) who had learned neither ultrasound techniques
      nor catheter insertion. The primary endpoint was time to successful puncture. We
      recorded age, sex, video game use, and the laterality of hands, feet and eyes.
      RESULTS: One left-handed and nine right-handed nurses were randomized to each
      group. Puncture by the non-dominant hand was significantly quicker in both series
      (P<0.001). There was no difference between groups for time to successful puncture
      with the dominant hand; however a significant difference was found for the non
      dominant hand (P<0.01). According to multivariate analysis, the time to
      successful puncture was significantly lower when the non-dominant hand was used
      to puncture (adjusted difference 5.6s, P<0.0001). CONCLUSION: Using the dominant
      hand to hold the ultrasound probe and the non-dominant hand to puncture and
      insert the catheter achieves successful insertion in a significantly shorter
      time.

PMID- 27876560
TI  - Subcutaneous rotenone rat model of Parkinson's disease: Dose exploration study.
AB  - Subcutaneous administration of rotenone has recently attracted attention because
      of its convenience, simplicity and efficacy in replicating features of
      Parkinson's disease (PD) in animal models. However, the wide range of doses
      reported in the literature makes it difficult to evaluate the effectiveness of
      this technique objectively. The aim of the present study was to identify the
      optimum dose of subcutaneous rotenone for establishing a model of PD. We injected
      male Wistar rats subcutaneously with one of three doses of rotenone (1.5, 2, or
      2.5mg/kg) daily for 5 weeks. Rotenone caused a dose-dependent increase in alpha
      synuclein in the substantia nigra. Furthermore, at 2 and 2.5mg/kg, rotenone
      caused a significant decrease in the number of tyrosine hydroxylase
      immunoreactive neurons in the substantia nigra, and dopamine in the striatum.
      However, mortality at 2.5mg/kg was 46.7%, compared with just 6.7% at 2mg/kg; the
      high mortality observed at 2.5mg/kg would limit its application. The 2mg/kg dose
      showed no detrimental effect on body weight after 5 weeks of daily injections.
      Furthermore, rats in the 2mg/kg group showed a longer latency to descend from a
      horizontal bar and a grid wall, decreased rearing, and shorter latency to fall
      from a rotarod than rats that received vehicle or saline. Mitochondrial damage,
      observed by transmission electron microscopy, was also evident at this dose.
      Together, our data indicate that daily subcutaneous injection of 2mg/kg rotenone
      in rats facilitates the formation of alpha-synuclein and reproduces the typical
      features of PD, while maintaining low mortality.

PMID- 27876557
TI  - Targeting nuclear thymidylate biosynthesis.
AB  - Thymidylate (dTMP) biosynthesis plays an essential and exclusive function in DNA
      synthesis and proper cell division, and therefore has been an attractive
      therapeutic target. Folate analogs, known as antifolates, and nucleotide analogs
      that inhibit the enzymatic action of the de novo thymidylate biosynthesis pathway
      and are commonly used in cancer treatment. In this review, we examine the
      mechanisms by which the antifolate 5-fluorouracil, as well as other dTMP
      synthesis inhibitors, function in cancer treatment in light of emerging evidence
      that dTMP synthesis occurs in the nucleus. Nuclear localization of the de novo
      dTMP synthesis pathway requires modification of the pathway enzymes by the small
      ubiquitin-like modifier (SUMO) protein. SUMOylation is required for nuclear
      localization of the de novo dTMP biosynthesis pathway, and disruption in the SUMO
      pathway inhibits cell proliferation in several cancer models. We summarize
      evidence that the nuclear localization of the dTMP biosynthesis pathway is a
      critical factor in the efficacy of antifolate-based therapies that target dTMP
      synthesis.

PMID- 27876561
TI  - Tip Design of Hemodialysis Catheters Influences Thrombotic Events and Replacement
      Rate.
AB  - OBJECTIVE/BACKGROUND: Central venous tunnelled hemodialysis catheters (CVTC) are
      used for initial vascular access in patients with renal failure. Tip design of
      the CVTC may play an important role in catheter function and complication rates,
      influencing adequate hemodialysis treatment of these patients. METHODS: This
      prospective, observational cohort study compared the function and complication
      rates of two CVTCs in patients with end stage renal disease (ESRD) within a
      follow-up period of 24 months. The study included patients with ESRD who received
      either a CVTC with a split tip (ST) or a shotgun tip (SG). All patients underwent
      dialysis within 24 h of intervention. Blood flow was documented initially (Qb0)
      and was followed up after 6 (Qb6), 12 (Qb12), and 24 (Qb24) months. Analysis of
      blood flow and complication rates within the follow-up period was performed by
      questionnaires. RESULTS: In total, 185 patients were included, of whom 93
      received a ST CVTC and 92 a SG CVTC. Baseline parameters did not differ
      significantly between groups. CVTC blood flow was not significantly different
      between the two devices. Thrombolytic therapy with Alteplase was used
      significantly more often in the ST group (29%) than in the SG group (16%) (p <
      0.05). The CVTC replacement rate was significantly higher in the ST group (19.3%)
      compared with the SG group (8.7%) (p < 0.05). CONCLUSIONS: The tip design of CVTC
      (split or shotgun) appears to be irrelevant for long-term blood flow during
      dialysis treatment. However, patients may benefit from SG catheters over ST
      catheters where replacement rates and thrombolytic treatment are concerned.

PMID- 27876562
TI  - Early Multiple Coronary Micro Aneurysms After Bioresorbable Vascular Scaffold
      Implantation.
AB  - Bioresorbable vascular scaffold (BVS) is a novel technology designed to overcome
      the long-term limitations of permanent metallic stent implantation in
      percutaneous coronary intervention. However, little is known about the
      development of coronary aneurysms after the use of BVSs, and additional
      experience is needed to establish the entire spectrum of complications related to
      the use of these emerging materials. We hereby report an unusual case of early
      multiple coronary artery micro aneurysms formation after BVS implantation.

PMID- 27876563
TI  - Preoperative Optimization of the Heart Failure Patient Undergoing Cardiac
      Surgery.
AB  - Heart failure patients who undergo cardiac surgery are exposed to significant
      perioperative complications and high mortality. We herein review the literature
      concerning preoperative optimization of these patients. Salient findings are that
      end-organ dysfunction and medication should be optimized before surgery.
      Specifically: (1) reversible causes of anemia should be treated and a
      preoperative hemoglobin level of 100 g/L obtained; (2) renal function and volume
      status should be optimized; (3) liver function must be carefully evaluated; (4)
      nutritional status should be assessed and cachexia treated to achieve a
      preoperative albumin level of at least 30 g/L and a body mass index > 20; and (5)
      medication adjustments performed, such as withholding inhibitors of the renin
      angiotensin-aldosterone system before surgery and continuing, but not starting,
      beta-blockers. Levels of natriuretic peptides (brain natriuretic peptide [BNP]
      and N-terminal proBNP) provide additional prognostic value and therefore should
      be measured. In addition, individual patient's risk should be objectively
      assessed using standard formulas such as the EuroSCORE-II or Society of Thoracic
      Surgeons risk scores, which are simple and validated for various cardiac
      surgeries, including left ventricular assist device implantation. When patients
      are identified as high risk, preoperative hemodynamic optimization might be
      achieved with the insertion of a pulmonary artery catheter and hemodynamic-based
      tailored therapy. Finally, a prophylactic intra-aortic balloon pump might be
      considered in certain circumstances to decrease morbidity and even mortality,
      like in some high risk heart failure patients who undergo cardiac surgery,
      whereas routine preoperative inotropes are not recommended and should be reserved
      for patients in shock, except maybe for levosimendan.

PMID- 27876564
TI  - RNCR3: A regulator of diabetes mellitus-related retinal microvascular
      dysfunction.
AB  - Retinal microvascular abnormality is an important pathological feature of
      diabetic retinopathy. Herein, we report the role of lncRNA-RNCR3 in diabetes
      mellitus-induced retinal microvascular abnormalities. We show that RNCR3 is
      significantly up-regulated upon high glucose stress in vivo and in vitro. RNCR3
      knockdown alleviates retinal vascular dysfunction in vivo, as shown by decreased
      acellular capillaries, decreased vascular leakage, and reduced inflammatory
      response. RNCR3 knockdown decreases retinal endothelial cell proliferation, and
      reduces cell migration and tube formation in vitro. RNCR3 regulates endothelial
      cell function through RNCR3/KLF2/miR-185-5p regulatory network. RNCR3 inhibition
      may be a treatment option for the prevention of diabetes mellitus-induced retinal
      microvascular abnormalities.

PMID- 27876565
TI  - Magnesium chloride and polyamine can differentiate mouse embryonic stem cells
      into trophectoderm or endoderm.
AB  - Magnesium chloride and polyamines stabilize DNA and chromatin. Furthermore, they
      can induce nucleosome aggregation and chromatin condensation in vitro. To
      determine the effects of elevating the cation concentrations in the nucleus of a
      living cell, we microinjected various concentrations of mono-, di- and polyvalent
      cation solutions into the nuclei of mouse embryonic stem (ES) cells and traced
      their fates. Here, we show that an elevation of either MgCl2, spermidine or
      spermine concentration in the nucleus exerts a significant effect on mouse ES
      cells, and can differentiate a certain population of the cells into
      trophectoderm, a lineage that mouse ES cells do not normally generate, or
      endoderm. It is hypothesized that the cell differentiation was most probably
      caused by the condensation of chromatin including the Oct3/4 locus, which was
      induced by the elevated concentrations of these cations.

PMID- 27876566
TI  - A novel recovery method of copper from waste printed circuit boards by
      supercritical methanol process: Preparation of ultrafine copper materials.
AB  - In this study, supercritical methanol (SCM) process was successfully used for the
      preparation of ultrafine copper materials from waste printed circuit boards
      (PCBs) after nitric acid pretreatment. Waste PCBs were pretreated twice in nitric
      acid. Sn and Pb were recovered by the first nitric acid pretreatment. The leach
      liquor with a high concentration of copper ions after the second nitric acid
      leaching was subjected to SCM process. The mixture of Cu and Cu2O with poor
      uniformity of particle size was formed due to the effect of ferric iron contained
      in the leach liquor of waste PCBs, while more uniform and spherical Cu particles
      with high monodispersity and smaller size could be prepared after the removal of
      Fe. The size of Cu particles increased obviously with the decline of SCM
      temperature, and particles became highly aggregated when the reaction temperature
      decreased to 300 degrees C. The size of Cu particles decreased markedly with the
      decrease of initial concentration of copper ion in the leach liquor of waste
      PCBs. It is believed that the process developed in this study is simple and
      practical for the preparation of ultrafine copper materials from waste PCBs with
      the aim of recycling these waste resources as a high value-added product.

PMID- 27876567
TI  - Improvement in CH4/CO2 ratio and CH4 yield as related to biomass mix composition
      during anaerobic co-digestion.
AB  - Sixteen data sets (two of which were measured in this study) with a combined
      total of 145 measurements of ultimate methane yield (UMY) during mono- and co
      digestion of ternary biomass mixtures were used to assess impact of co-digestion
      on the relative change in UMY (DeltaUMY) as a function of biomass mix
      composition. The data involved 9 biomass materials (brewery spent grains, chicken
      manure, cow manure, fresh grass clippings, pig manure, primary sewage sludge,
      vegetable food waste, wheat straw, and rice straw). Results of the assessment
      shows that co-digestion in 85% of yields positive values of DeltaUMY regardless
      of the biomass materials used, however, a smaller fraction (15%) resulted in
      negative DeltaUMY during co-digestion. The data further indicate that for each
      set of ternary biomass material mixtures there exists an optimal biomass mix
      composition at which DeltaUMY is at a maximum. Statistical analyses based on the
      data used here indicate that the maximum value of DeltaUMY (DeltaUMYmax) is
      always positive regardless of biomass materials being co-digested.

PMID- 27876568
TI  - Design, synthesis, and biological evaluation of steroidal analogs as
      estrogenic/anti-estrogenic agents.
AB  - Series of estrone based analogs were synthetically investigated at positions C-9,
      C-11, C-16, and C-17 positions, to be biologically evaluated via assessment of
      cell proliferation, cytotoxicity, and estrogenic/anti-estrogenic activity. LA-7
      and LA-10 revealed their potential to exhibit inhibitory estrogenic profile. This
      was further validated by Estrogen Receptor-alpha (ER-alpha) and Estrogen Receptor
      beta (ER-beta) competitive binding assays to reveal the high selective affinity
      of LA-7 towards ER-alpha at 5.49MUM, while LA-10 did not show any binding
      affinity towards neither ER-alpha nor ER-beta; suggesting another mechanism for
      inhibition. This was validated by in silico molecular docking simulations of LA-7
      to reveal the optimum binding affinity of LA-7 towards ER-alpha.

PMID- 27876569
TI  - O-space with high resolution readouts outperforms radial imaging.
AB  - PURPOSE: While O-Space imaging is well known to accelerate image acquisition
      beyond traditional Cartesian sampling, its advantages compared to undersampled
      radial imaging, the linear trajectory most akin to O-Space imaging, have not been
      detailed. In addition, previous studies have focused on ultrafast imaging with
      very high acceleration factors and relatively low resolution. The purpose of this
      work is to directly compare O-Space and radial imaging in their potential to
      deliver highly undersampled images of high resolution and minimal artifacts, as
      needed for diagnostic applications. We report that the greatest advantages to O
      Space imaging are observed with extended data acquisition readouts. THEORY AND
      METHODS: A sampling strategy that uses high resolution readouts is presented and
      applied to compare the potential of radial and O-Space sequences to generate high
      resolution images at high undersampling factors. Simulations and phantom studies
      were performed to investigate whether use of extended readout windows in O-Space
      imaging would increase k-space sampling and improve image quality, compared to
      radial imaging. RESULTS: Experimental O-Space images acquired with high
      resolution readouts show fewer artifacts and greater sharpness than radial
      imaging with equivalent scan parameters. Radial images taken with longer readouts
      show stronger undersampling artifacts, which can cause small or subtle image
      features to disappear. These features are preserved in a comparable O-Space
      image. CONCLUSIONS: High resolution O-Space imaging yields highly undersampled
      images of high resolution and minimal artifacts. The additional nonlinear
      gradient field improves image quality beyond conventional radial imaging.

PMID- 27876570
TI  - Characterization of the anti-inflammation mechanism for the AO herbal extract.
AB  - A broad range of cytokines are secreted during the inflammatory response by the
      immune system. Some cytokines promote inflammation, while others inhibit
      inflammation. Inflammatory cytokines work in harmony when they encounter external
      pathogens or internal dangers. Inflammation is resolved after the cause is
      eliminated. However, if the cause persists, it can lead to significant diseases.
      The pro-inflammatory cytokine TNFalpha is a biomarker for the inflammatory
      response. The AO herbal mixture extracted from 10 medicinal herbs has been
      investigated for its ability to control the inflammatory process and to inhibit
      TNFalpha activity. To find the treatment for inflammation related diseases, we
      examined whether the AO herbal extract is able to affect the activities of other
      cytokines. Here we present that the AO herbal extract is able to inhibit pro
      inflammatory factor activities including IL-1alpha. However, it does not affect
      the activities of IL-1beta and IL-6. Interestingly, it promotes the activity of
      anti-inflammatory factors including IL-4 and IL-13.

PMID- 27876572
TI  - [Familial EXOSC3-related pontocerebellar hypoplasia].

PMID- 27876571
TI  - Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and
      Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear
      Factor-kappaB, and Up-regulating Expression of MicroRNA-21.
AB  - BACKGROUND & AIMS: Nearly 20% of the global cancer burden can be linked to
      infectious agents. Fusobacterium nucleatum promotes tumor formation by epithelial
      cells via unclear mechanisms. We aimed to identify microRNAs (miRNAs) induced by
      F nucleatum and evaluate their ability to promote colorectal carcinogenesis in
      mice. METHODS: Colorectal cancer (CRC) cell lines were incubated with F nucleatum
      or control reagents and analyzed in proliferation and would healing assays.
      HCT116, HT29, LoVo, and SW480 CRC cell lines were incubated with F nucleatum or
      phosphate-buffered saline (PBS [control]) and analyzed for miRNA expression
      patterns and in chromatin immunoprecipitation assays. Cells were incubated with
      miRNAs mimics, control sequences, or small interfering RNAs; expression of
      reporter constructs was measured in luciferase assays. CRC cells were incubated
      with F nucleatum or PBS and injected into BALB/C nude mice; growth of xenograft
      tumors was measured. C57BL adenomatous polyposis colimin/+, C57BL miR21a-/-, and
      C57BL mice with full-length miR21a (controls) were given F nucleatum by gavage;
      some mice were given azoxymethane and dextran sodium sulfate to induce colitis
      and colon tumors. Intestinal tissues were collected and tumors were counted.
      Serum samples from mice were analyzed for cytokine levels by enzyme-linked
      immunosorbent assay. We performed in situ hybridization analyses to detect
      enrichment of F nucleatum in CRC cells. Fusobacterium nucleatum DNA in 90 tumor
      and matched nontumor tissues from patients in China were explored for the
      expression correlation analysis; levels in 125 tumor tissues from patients in
      Japan were compared with their survival times. RESULTS: Fusobacterium nucleatum
      increased proliferation and invasive activities of CRC cell lines compared with
      control cells. CRC cell lines infected with F nucleatum formed larger tumors,
      more rapidly, in nude mice than uninfected cells. Adenomatous polyposis colimin/+
      mice gavaged with F nucleatum developed significantly more colorectal tumors than
      mice given PBS and had shorter survival times. We found several inflammatory
      factors to be significantly increased in serum from mice given F nucleatum
      (interleukin 17F, interleukin 21, and interleukin 22, and MIP3A). We found 50
      miRNAs to be significantly up-regulated and 52 miRNAs to be significantly down
      regulated in CRCs incubated with F nucleatum vs PBS; levels of miR21 increased by
      the greatest amount (>4-fold). Inhibitors of miR21 prevented F nucleatum from
      inducing cell proliferation and invasion in culture. miR21a-/- mice had a later
      appearance of fecal blood and diarrhea after administration of azoxymethane and
      dextran sodium sulfate, and had longer survival times compared with control mice.
      The colorectum of miR21a-/- mice had fewer tumors, of smaller size, and the
      miR21a-/- mice survived longer than control mice. We found RASA1, which encodes
      an RAS GTPase, to be one of the target genes consistently down-regulated in cells
      that overexpressed miR21 and up-regulated in cells exposed to miR21 inhibitors.
      Infection of cells with F nucleatum increased expression of miR21 by activating
      Toll-like receptor 4 signaling to MYD88, leading to activation of the nuclear
      factor-kappaB. Levels of F nucleatum DNA and miR21 were increased in tumor
      tissues (and even more so in advanced tumor tissues) compared with non-tumor
      colon tissues from patients. Patients whose tumors had high amounts of F
      nucleatum DNA and miR21 had shorter survival times than patients whose tumors had
      lower amounts. CONCLUSIONS: We found infection of CRC cells with F nucleatum to
      increase their proliferation, invasive activity, and ability to form xenograft
      tumors in mice. Fusobacterium nucleatum activates Toll-like receptor 4 signaling
      to MYD88, leading to activation of the nuclear factor-kappaB and increased
      expression of miR21; this miRNA reduces levels of the RAS GTPase RASA1. Patients
      with both high amount of tissue F nucleatum DNA and miR21 demonstrated a higher
      risk for poor outcomes.

PMID- 27876574
TI  - The emerging role of ECM crosslinking in T cell mobility as a hallmark of
      immunosenescence in humans.
AB  - Immunosenescence is thought to result from cellular aging and to reflect exposure
      to environmental stressors and antigens, including cytomegalovirus (CMV).
      However, not all of the features of immunosenescence are consistent with this
      view, and this has led to the emergence of the sister theory of "inflammaging".
      The recently discovered diffuse tissue distribution of resident memory T cells
      (TRM) which don't recirculate, calls these theories into question. These cells
      account for most T cells residing in barrier epithelia which sit in and travel
      through the extracellular matrix (ECM). With almost all studies to date carried
      out on peripheral blood, the age-related changes of the ECM and their
      consequences for T cell mobility, which is crucial for the function of these
      cells, have been largely ignored. We propose an update of the theoretical
      framework of immunosenescence, based on a novel hypothesis: the increasing
      stiffness and cross-linking of the senescent ECM lead to a progressive
      immunodeficiency due to an age-related decrease in T cell mobility and eventually
      the death of these cells. A key element of this mechanism is the mechanical
      stress to which the cell cytoplasm and nucleus are subjected during passage
      through the ECM. This hypothesis is based on an "evo-devo" perspective bringing
      together some major characteristics of aging, to create a single interpretive
      framework for immunosenescence.

PMID- 27876575
TI  - Effects of collagen membrane application and cortical bone perforation on de novo
      bone formation in periosteal distraction: an experimental study in a rabbit
      calvaria.
AB  - OBJECTIVES: The aim of the present study was to assess the impact of collagen
      membrane application and cortical bone perforations in periosteal distraction
      osteogenesis. STUDY DESIGN: A total of 32 New Zealand rabbits were randomized
      into four experimental groups, considering two treatment modalities. Calvarial
      bone was perforated or left intact (P+/-). In half the animals, the distraction
      mesh was covered with a collagen membrane (M+/-). All animals were subjected to a
      7-day latency period and a 10-day distraction period. The samples were harvested
      after 4-week and 8-week consolidation periods and analyzed histologically and by
      means of micro-computed tomography. RESULTS: Primary, woven bone observed at the
      4-week consolidation period was gradually replaced by lamellar bone at the 8-week
      consolidation period. Significant increase in bone volume was found in all groups
      (P < .001) and in bone mineral density in groups I (P-/M-; P < .001), III (P+/M-;
      P < .001), and IV (P+/M+; P = .013). Group III (P+/M-) showed significantly more
      new bone at the 8-week consolidation period compared with the other three groups
      (P = .001), with no differences observed in bone mineral density between groups
      at a given time-point. CONCLUSIONS: In the present model, cortical bone
      perforations have more impact on the osteogenic process compared with the
      application of a collagen membrane.

PMID- 27876577
TI  - Reply to "Comments on 'Imaging features of medicine-related osteonecrosis of the
      jaws: comparison between panoramic radiography and computed tomography'".

PMID- 27876578
TI  - Response to "Comment on 'Establishing a targeted plan for prophylactic dental
      extractions in patients with laryngeal cancer receiving adjuvant radiotherapy'".

PMID- 27876576
TI  - The bone regenerative capacity of canine mesenchymal stem cells is regulated by
      site-specific multilineage differentiation.
AB  - OBJECTIVES: Mesenchymal stem cells (MSCs) offer a promising therapy in dentistry
      because of their multipotent properties. Selecting donor MSCs is crucial because
      Beagle dogs (canines) commonly used in preclinical studies have shown variable
      outcomes, and it is unclear whether canine MSCs (cMSCs) are skeletal site
      specific. This study tested whether jaw and long bone cMSCs have disparate in
      vitro and in vivo multilineage differentiation capabilities. STUDY DESIGN:
      Primary cMSCs were isolated from the mandible (M-cMSCs) and femur (F-cMSCs) of
      four healthy Beagle dogs. The femur served as the non-oral control. Clonogenic
      and proliferative abilities were assessed. In vitro osteogenic, chondrogenic,
      adipogenic, and neural multilineage differentiation were correlated with in vivo
      bone regeneration and potential for clinical applications. RESULTS: M-cMSCs
      displayed two-fold increase in clonogenic and proliferative capacities relative
      to F-cMSCs (P = .006). M-cMSCs in vitro osteogenesis based on alkaline
      phosphatase (P = .04), bone sialoprotein (P = .05), and osteocalcin (P = .03), as
      well as adipogenesis (P = .007) and chondrogenesis (P = .009), were relatively
      higher and correlated with enhanced M-cMSC bone regenerative capacity. Neural
      expression markers, nestin and betaIII-tubulin, were not significantly different.
      CONCLUSIONS: The enhanced differentiation and bone regenerative capacity of
      mandible MSCs may make them favorable donor graft materials for site-specific jaw
      bone regeneration.

PMID- 27876579
TI  - Comment on "Establishing a targeted plan for prophylactic dental extractions in
      patients with laryngeal cancer receiving adjuvant radiotherapy".

PMID- 27876573
TI  - Stem cell therapies in age-related neurodegenerative diseases and stroke.
AB  - Aging, a complex process associated with various structural, functional and
      metabolic changes in the brain, is an important risk factor for neurodegenerative
      diseases and stroke. These diseases share similar neuropathological changes, such
      as the formation of misfolded proteins, oxidative stress, loss of neurons and
      synapses, dysfunction of the neurovascular unit (NVU), reduction of self-repair
      capacity, and motor and/or cognitive deficiencies. In addition to gray matter
      dysfunction, the plasticity and repair capacity of white matter also decrease
      with aging and contribute to neurodegenerative diseases. Aging not only renders
      patients more susceptible to these disorders, but also attenuates their self
      repair capabilities. In addition, low drug responsiveness and intolerable side
      effects are major challenges in the prevention and treatment of senile diseases.
      Thus, stem cell therapies-characterized by cellular plasticity and the ability to
      self-renew-may be a promising strategy for aging-related brain disorders. Here,
      we review the common pathophysiological changes, treatments, and the promises and
      limitations of stem cell therapies in age-related neurodegenerative diseases and
      stroke.

PMID- 27876580
TI  - Management of dry mouth: assessment of oral symptoms after use of a
      polysaccharide-based oral rinse.
AB  - OBJECTIVE: Salivary dysfunction is associated with a range of oral/dental issues,
      and management of oral symptoms may improve oral function and overall quality of
      life. The purpose of this pilot study was to evaluate oral symptoms and function
      in a xerostomic population after use of a proprietary topical for dry mouth,
      Moisyn (Synedgen Inc., Claremont, CA), which is a polysaccharide-based product.
      STUDY DESIGN: A pre- and post-test survey was completed by 57 patients with
      xerostomia. Patients rated their common oral symptoms, based on the Vanderbilt
      Head and Neck Symptom Survey, before and after 1-week use of Moisyn rinse and
      spray. Saliva production under resting and chewing stimulation was also assessed.
      RESULTS: Most patients reported relief from dry mouth symptoms and thick saliva
      (81.7% and 76.0%, respectively) for more than 30 minutes after product use.
      Statistically significant reductions were found in 15 of 33 oral symptoms.
      Symptom improvement ranged from 10.7% to 28.4% for thick saliva, 8.4% to 30.6%
      for pain, 5.5% to 30.4% for dry mouth, and 12% to 21.3% for taste/diet change.
      Whole unstimulated/resting saliva improved by 100%, and whole stimulated saliva
      improved by 23.8%. CONCLUSIONS: These findings suggest that the product has
      utility in symptom control in patients with xerostomia and may lead to an
      increase in saliva production.

PMID- 27876581
TI  - Valley of death: A proposal to build a "translational bridge" for the next
      generation.
AB  - There is a great need for novel drug discovery for major mental illnesses, but
      multiple levels of challenges exist in both academia and industry, spanning from
      scientific understanding and institutional infrastructure to business risk and
      feasibility. The "valley of death," the large gap between basic scientific
      research and translation to novel therapeutics, underscores the need to
      restructure education and academic research to cultivate the fertile interface
      between academia and industry. In this opinion piece, we propose strategies to
      educate young trainees in the process of drug discovery and development, and
      prepare them for careers across this spectrum. In addition, we describe a
      research framework that considers the disease trajectory and underlying biology
      of mental disorders, which will help to address the core pathophysiology in novel
      treatments, and may even allow early detection and intervention. We hope that
      these changes will increase understanding among academia, industry, and
      government, which will ultimately improve the diagnosis, prognosis and treatment
      of mental disorders.

PMID- 27876582
TI  - Subperitoneal approach in revision arthroplasty for acetabular component
      protrusion: Analysis of practices within the French Hip and Knee Society (SFHG).
AB  - INTRODUCTION: The complications related to revision for acetabular component
      protrusion with material migrating into the intrapelvic region remain rare but
      potentially serious. Today, the literature reports no epidemiological data on the
      subperitoneal approach (SPA) in revision total hip arthroplasty (RTHA) for
      protrusion. Therefore we conducted a retrospective study on a large revision
      arthroplasty database to answer the following questions: (1) What is the
      frequency of this approach in this population? (2) What are the factors related
      to this procedure? (3) Is morbidity and mortality of the SPA higher than for an
      isolated conventional approach? HYPOTHESIS: Major protrusions with material in
      the superomedial quadrant (SMQ) have a higher probability of being operated using
      a SPA. MATERIAL AND METHODS: This multicenter retrospective study included 260
      cases of THA with endopelvic protrusion of material at least 15mm inside the
      Kohler line. The degree of protrusion was assessed on the AP pelvic X-ray with
      the construction of the SMQ. The reason for the subperitoneal approach, the
      duration of surgery, and the preoperative exams were also collected. RESULTS:
      Nineteen procedures out of the 260 RTHAs included (7.8%) had a SPA in addition to
      the approach for the revision THA. The frequency of the SPA varied among centers
      (range: 1.7-50%). In four cases, the SPA was indicted to care for a vascular
      complication identified preoperatively. For one patient, the SPA was indicated
      intraoperatively. The other indications were either to extract the implant (n=7)
      or prevent a potential intraoperative assault of neurovascular structures (n=9).
      The cases presenting major protrusion on the AP X-ray with material in the SMQ
      were more often operated through the SPA (12/19; 63.2%) than cases with no SMQ
      involvement (4/241; 1.7%) (P<0.001). Vascular structures were explored with
      imaging in 15 out of 19 (88.9%) of the SPA cases versus 26 out of 177 (14.7%) of
      the revisions without the SPA (41 with no information in the non-SPA group)
      (P<0.001). Early mortality (before 45 days) of patients who had undergone the SPA
      (1/19; 5.3%) was not significantly different than for the patients who had not
      undergone the SPA (3/241; 1.2%) (P=0.26). Although the duration of surgery was
      longer in the SPA group (210+/-88 [range: 70-360] versus 169+/-52 [range: 60
      300]; P=0.04), bleeding was not greater in the SPA group (1488+/-1770mL [range:
      500-5000mL]) than in the non-SPA group (1343+/-987mL [range: 75-3500mL]; p>0.05).
      DISCUSSION: Despite the limitations related to the retrospective and multicenter
      design of this study, to our knowledge it is the only one that examines SPA
      procedures within the context of severe material protrusion with THA. Based on
      these results, it seems preferable to plan for SPA every time there is an
      acetabular protrusion in the SMQ, after exploration with CT angiography. The SPA
      does not result in greater mortality or morbidity. LEVEL OF EVIDENCE: IV,
      retrospective study.

PMID- 27876583
TI  - Treatment of pediatric forearm midshaft fractures: Is there a difference between
      types of orthopedic surgeon?
AB  - PURPOSE OF THE STUDY: The objective of this study was to compare the clinical and
      radiological outcomes of pediatric forearm midshaft fractures treated operatively
      with titanium elastic nails (TENs) by pediatric orthopedists and non-pediatric
      orthopedists. MATERIAL AND METHODS: We conducted a prospective cohort study of 88
      children of forearm midshaft fractures, who were randomized to operative
      stabilization either by pediatric orthopedists (Group A, 44 cases) or by non
      pediatric orthopedists (Group B, 44 cases) from April 2013 to February 2014. At
      baseline, the groups were comparable with respect to age, sex, AO classification,
      injured side and interval from injury to surgery. We collected data on operative
      and radiation time, open reduction rate, length of hospitalization, bone union
      time, return to full physical activity time, complications, and measured clinical
      results using the Children's Hospital of Philadelphia (CHOP) Forearm Fracture
      Fixation Outcome Classification. RESULTS: The mean follow-up period was 15.8+/
      3.3 months for Group A and 15.2+/-4.2 months for Group B (P=0.491). No
      significant difference existed in time to union (P=0.282), the overall
      complication rate (P=0.750), return to activity time (P=0.408), and clinical
      outcomes according to CHOP classification (P=0.908) between the two groups.
      However, the mean operating time and radiation time was significantly longer in
      Group B than in Group A (P=0.001 and P=0.001, respectively). In addition, there
      was a trend for patients of Group B to have a higher rate of open reduction
      (P=0.035). DISCUSSIONS: Our results indicated that children forearm midshaft
      fractures treated surgically by pediatric orthopedists offered potential
      advantages including a shorter operating time and radiation time, a lower rate of
      open reduction. However, both pediatric and non-pediatric orthopedists had
      achieved satisfactory clinical results in treatment of these injuries. LEVEL OF
      EVIDENCE: Level II prospective randomized study.

PMID- 27876584
TI  - Investigation and prediction of protein precipitation by polyethylene glycol
      using quantitative structure-activity relationship models.
AB  - Precipitation of proteins is considered to be an effective purification method
      for proteins and has proven its potential to replace costly chromatography
      processes. Besides salts and polyelectrolytes, polymers, such as polyethylene
      glycol (PEG), are commonly used for precipitation applications under mild
      conditions. Process development, however, for protein precipitation steps still
      is based mainly on heuristic approaches and high-throughput experimentation due
      to a lack of understanding of the underlying mechanisms. In this work we apply
      quantitative structure-activity relationships (QSARs) to model two parameters,
      the discontinuity point m* and the beta-value, that describe the complete
      precipitation curve of a protein under defined conditions. The generated QSAR
      models are sensitive to the protein type, pH, and ionic strength. It was found
      that the discontinuity point m* is mainly dependent on protein molecular
      structure properties and electrostatic surface properties, whereas the beta-value
      is influenced by the variance in electrostatics and hydrophobicity on the protein
      surface. The models for m* and the beta-value exhibit a good correlation between
      observed and predicted data with a coefficient of determination of R2>=0.90 and,
      hence, are able to accurately predict precipitation curves for proteins. The
      predictive capabilities were demonstrated for a set of combinations of protein
      type, pH, and ionic strength not included in the generation of the models and
      good agreement between predicted and experimental data was achieved.

PMID- 27876585
TI  - Pediatric Asthma Health Disparities: Race, Hardship, Housing, and Asthma in a
      National Survey.
AB  - OBJECTIVE: We sought to determine if racial disparities in pediatric asthma are
      explained by material hardship and home ownership. METHODS: We performed a
      secondary analysis of the 2011 American Housing Survey. A total of 33,201
      households with children age 6 to 17 years were surveyed regarding childhood
      asthma diagnosis and emergency department (ED) visits for asthma (for the
      youngest child with asthma in the household). Material hardship included poor
      housing quality, housing crowding, lack of amenities, and no vehicle access. We
      used logistic regression to determine the association between race, material
      hardship, and asthma diagnosis or ED visits, adjusting for potential confounders.
      RESULTS: Non-Hispanic black heads of household had a higher odds of having a
      child diagnosed with asthma in the home compared with non-Hispanic white heads of
      household (odds ratio, 1.72; 95% confidence interval [CI], 1.50-1.96), and a
      higher odds of ED visits for asthma (odds ratio, 3.02; 95% CI, 2.29-3.99). The
      race-asthma association was decreased but not eliminated after adjusting for
      material hardship and home ownership (ED visit adjusted odds ratio [AOR], 2.07;
      95% CI, 1.50-2.86). Poor housing quality was independently associated with asthma
      diagnosis (AOR, 1.45; 95% CI, 1.28-1.66) and ED visits (AOR, 1.59; 95% CI, 1.21
      2.10). Home ownership was associated with a lower odds of asthma-related ED
      visits (AOR, 0.62; 95% CI, 0.46-0.84). CONCLUSIONS: Observed racial disparities
      in pediatric asthma are lessened after controlling for material hardship. Poor
      housing quality in particular is strongly associated with asthma morbidity.
      Policy makers could target improving housing quality as a means of potentially
      reducing asthma disparities.

PMID- 27876586
TI  - Fluoride Supplementation Adherence and Barriers in a Community Without Water
      Fluoridation.
AB  - BACKGROUND: To prevent early childhood caries, the American Dental Association
      recommends oral fluoride supplementation for children in communities lacking
      water fluoridation who are at high caries risk. However, patient adherence to
      oral fluoride supplementation has not been studied in this population. This study
      assessed adherence to oral fluoride and barriers to adherence in a community
      lacking water fluoridation. METHODS: A self-administered survey was completed in
      a systematic sample of 209 parents of children aged 6 months to 4 years, during a
      primary care visit in an urban academic medical center. Participants reported
      frequency of administering oral fluoride to their children, as well as agreement
      or disagreement with proposed barriers to supplementation. Bivariate and
      multivariate analyses were used to assess adherence with oral supplementation and
      the association of barriers to supplementation and child receipt of fluoride on
      the day before. RESULTS: More than half of parents either had not or did not know
      if their child had received fluoride on the day before. Approximately 1 in 4 of
      parents had given fluoride in 0 of the previous 7 days. Difficulty remembering to
      give fluoride and agreeing that the child does not need extra fluoride were
      associated with not receiving fluoride on the day before. CONCLUSIONS: Adherence
      to oral fluoride supplementation in the primary care setting is low. Difficulty
      remembering to give fluoride daily is the greatest barrier to adherence. Further
      research on interventions to reduce common barriers is needed to increase
      fluoride administration and reduce early childhood caries in communities lacking
      water fluoridation.

PMID- 27876587
TI  - Using Your Personal Mission Statement to INSPIRE and Achieve Success.

PMID- 27876588
TI  - Predicting Subsequent High-Frequency, Low-Acuity Utilization of the Pediatric
      Emergency Department.
AB  - OBJECTIVE: To derive and test a predictive model for high-frequency (4 or more
      visits per year), low-acuity (emergency severity index 4 or 5) utilization of the
      pediatric emergency department. METHODS: The study sample used 3 years of data
      (2012-2014) from a single tertiary-care children's hospital for patients <21
      years of age. Utilization in 2013 defined the index visit; prior utilization was
      drawn from 2012; and 2014 was used for outcome measurement. Candidate predictor
      variables were those that would be available at the time of triage. Data were
      split into derivation and test sets randomly; variables with a significant
      univariate association in the derivation set were included for multivariable
      modeling. The final model from the derivation set was then tested in the
      validation set, with calculation of a receiver operating characteristic curve.
      RESULTS: There were 90,972 visits in 2013, of which 61,430 were first (index)
      visits. A total of 590 (1%) had 4 or more triage level 4 or 5 visits in the
      following year (2014). The final model included site of primary care, age,
      acuity, previous utilization, race, and insurance, and had an area under the
      receiver operating characteristic curve of 0.84. CONCLUSIONS: Data available to
      the emergency department provider at the time of initial visit triage can predict
      utilization for low-acuity complaints in the subsequent year. Future work should
      focus on validation and refinement of the model in additional settings, and
      electronic calculation of risk status for targeted intervention to improve
      appropriate utilization of health care services.

PMID- 27876589
TI  - US Hospitalizations for Malignant Pleural Effusions: Data From the 2012 National
      Inpatient Sample.
AB  - BACKGROUND: Malignant pleural effusion (MPE) is a common complication of advanced
      malignancy, but little is known regarding its prevalence and overall burden on a
      population level. METHODS: We conducted a retrospective analysis of MPE
      associated hospitalizations using the Healthcare Cost and Utilization Project
      Nationwide Inpatient Sample, Agency for Healthcare Research and Quality (HCUP-NIS
      2012). Cases were included if MPE was coded as a primary or secondary diagnosis
      or if an unspecified pleural effusion was coded in addition to a diagnosis of
      cancer with either of these being the primary diagnosis. RESULTS: A weighted
      sample of 126,825 admissions (0.35%) for MPE was identified among the 36,484,846
      weighted admissions included in the database in 2012. Of these admissions, 70,750
      (55.8%) were for female patients. The median age at admission was 68.0 years
      (interquartile range [IQR]), 58.4-77.2 years). Lung (37.8%), breast (15.2%),
      hematologic (11.2%), GI tract (11.0%), and gynecologic (9.0%) cancers were the
      most common primary malignancies associated with MPE. The median length of stay
      was 5.5 days (IQR, 2.7-10.1 days), and the inpatient mortality rate was 11.6%.
      Median hospitalization total charges were $42,376 (IQR, $21,618-$84,679). In the
      multivariate analyses, female sex, large fringe county residential area, Medicare
      insurance, and elective type of admission were independently associated with a
      lower risk of inpatient mortality. CONCLUSIONS: There is a considerable inpatient
      burden and high inpatient mortality associated with MPE in the United States,
      with potential demographic, geographic, and socioeconomic disparities.

PMID- 27876590
TI  - Clinical Prognosis of Nonmassive Central and Noncentral Pulmonary Embolism: A
      Registry-Based Cohort Study.
AB  - BACKGROUND: Whether the localization of nonmassive pulmonary embolism (PE) is
      associated with the short-term and long-term prognosis of patients remains
      unknown. Our aim was to characterize associations of nonmassive PE localization
      with risks of recurrent VTE, major bleeding, and mortality during and after
      anticoagulation. METHODS: Among participants of the Registro Informatizado de la
      Enfermedad ThromboEmbolica (RIETE) registry with incident symptomatic nonmassive
      PE diagnosed by CT scan, we compared risks of recurrent VTE, major bleeding, and
      mortality during and after anticoagulation between central PE (main pulmonary
      artery) and noncentral PE (more peripheral arteries) using Cox proportional
      hazard-adjusted models. RESULTS: Of the 6,674 participants, patients with central
      PE (40.5%) had age (mean 66 years), sex (46.9% male sex), and proportion of
      idiopathic (45.0%) and cancer-related (22.3%) PE that were similar to those of
      patients with noncentral PE. During anticoagulation (5,256.1 patient-years), the
      risk of recurrent VTE was similar between the two groups (2.5 vs 2.1 per 100
      patient-years; adjusted hazard ratio [aHR], 1.32; 95% CI, 0.91-1.90), as were
      risks of major bleeding and mortality. After anticoagulation was discontinued
      (2,175.4 patient-years), participants with central PE had a borderline greater
      risk of recurrent VTE than did participants with noncentral PE (11.0 vs 8.0 per
      100 patient-years; aHR, 1.34; 95% CI, 1.01-1.78) but not when restricted to
      participants after unprovoked PE (13.8 vs 11.9 per 100 patient-years; aHR, 1.15;
      95% CI, 0.79-1.68; P = .48). Risks of major bleeding and mortality were similar.
      CONCLUSIONS: In nonmassive PE, central localization of PE is associated with
      greater risk of recurrent VTE after anticoagulation cessation. However, the low
      magnitude of this association and the absence of association after unprovoked PE
      suggest that the clinical relevance of this finding is limited and that the
      duration of anticoagulation should not be tailored to PE localization after
      nonmassive unprovoked PE.

PMID- 27876592
TI  - Systemic Inflammatory Response Syndrome, Quick Sequential Organ Function
      Assessment, and Organ Dysfunction: Insights From a Prospective Database of ED
      Patients With Infection.
AB  - BACKGROUND: A proposed revision of sepsis definitions has abandoned the systemic
      inflammatory response syndrome (SIRS), defined organ dysfunction as an increase
      in total Sequential Organ Function Assessment (SOFA) score of >= 2, and conceived
      "qSOFA" (quick SOFA) as a bedside indicator of organ dysfunction. We aimed to (1)
      determine the prognostic impact of SIRS, (2) compare the diagnostic accuracy of
      SIRS and qSOFA for organ dysfunction, and (3) compare standard (Sepsis-2) and
      revised (Sepsis-3) definitions for organ dysfunction in ED patients with
      infection. METHODS: Consecutive ED patients admitted with presumed infection were
      prospectively enrolled over 3 years. Sufficient observational data were collected
      to calculate SIRS, qSOFA, SOFA, comorbidity, and mortality. RESULTS: We enrolled
      8,871 patients, with SIRS present in 4,176 (47.1%). SIRS was associated with
      increased risk of organ dysfunction (relative risk [RR] 3.5) and mortality in
      patients without organ dysfunction (OR 3.2). SIRS and qSOFA showed similar
      discrimination for organ dysfunction (area under the receiver operating
      characteristic curve, 0.72 vs 0.73). qSOFA was specific but poorly sensitive for
      organ dysfunction (96.1% and 29.7%, respectively). Mortality for patients with
      organ dysfunction was similar for Sepsis-2 and Sepsis-3 (12.5% and 11.4%,
      respectively), although 29% of patients with Sepsis-3 organ dysfunction did not
      meet Sepsis-2 criteria. Increasing numbers of Sepsis-2 organ system dysfunctions
      were associated with greater mortality. CONCLUSIONS: SIRS was associated with
      organ dysfunction and mortality, and abandoning the concept appears premature. A
      qSOFA score >= 2 showed high specificity, but poor sensitivity may limit utility
      as a bedside screening method. Although mortality for organ dysfunction was
      comparable between Sepsis-2 and Sepsis-3, more prognostic and clinical
      information is conveyed using Sepsis-2 regarding number and type of organ
      dysfunctions. The SOFA score may require recalibration.

PMID- 27876593
TI  - Intact interferon-gamma response against Coxiella burnetii by peripheral blood
      mononuclear cells in chronic Q fever.
AB  - OBJECTIVES: Q fever is caused by Coxiella burnetii, an intracellular bacterium
      that infects phagocytes. The aim of the present study was to investigate whether
      the C. burnetii-induced IFN-gamma response is defective in chronic Q fever
      patients. METHODS: IFN-gamma was measured in supernatants of C. burnetii
      stimulated peripheral blood mononuclear cells (PBMCs) of 17 chronic Q fever
      patients and 17 healthy individuals. To assess IFN-gamma responses, expression
      profiles of IFN-gamma-induced genes in C. burnetii-stimulated PBMCs were studied
      in six patients and four healthy individuals. Neopterin was measured in PBMC
      supernatants (of eight patients and four healthy individuals) and in sera (of 21
      patients and 11 healthy individuals). In a genetic association study,
      polymorphisms in genes involved in the Th1-cytokine response were analysed in a
      cohort of 139 chronic Q fever patients and a cohort of 220 control individuals
      with previous exposition to C. burnetii. RESULTS: IFN-gamma production by C.
      burnetii-stimulated PBMCs from chronic Q fever patients was significantly higher
      than in healthy controls. Many IFN-gamma response genes were strongly upregulated
      in PBMCs of patients. Neopterin levels were significantly higher in PBMC
      supernatants and sera of patients. The IL12B polymorphisms rs3212227 and
      rs2853694 were associated with chronic Q fever. CONCLUSIONS: IFN-gamma
      production, as well as the response to IFN-gamma, is intact in chronic Q fever
      patients, and even higher than in healthy individuals. Polymorphisms in the IL
      12p40 gene are associated with chronic Q fever. Thus, a deficiency in IFN-gamma
      responses does not explain the failure to clear the infection. The genetic data
      suggest, however, that the IL-12/IFN-gamma pathway does play a role.

PMID- 27876594
TI  - Successful control of a large outbreak of HIV infection associated with injection
      of cathinone derivatives in Tel Aviv, Israel.
AB  - OBJECTIVES: Outbreaks of HIV infection have been linked to injectable drug abuse,
      but specific triggers often remain obscure. We report on an outbreak of primary
      HIV infection among people who inject drugs (PWID) in Tel Aviv, associated with a
      local shift in drug-use practices. METHODS: A cluster of primary HIV infection
      cases in PWID was detected in May 2012. Retrospective and prospective multi
      hospital case finding was initiated. PWID were interviewed and risk factors for
      primary HIV infection were identified. Starting in December 2012, a multifaceted
      intervention was implemented, including educational activities, increasing
      syringe exchange supplies, active screening, early initiation of antiretroviral
      therapy, and referral to drug withdrawal programmes. RESULTS: Forty-two PWID with
      primary HIV infection were detected between May 2012 and April 2013. Compared
      with the corresponding pre-outbreak period, the annual incidence of primary HIV
      infection in PWID increased from 0 to 20 cases/1000 population (p <0.0001). Sixty
      nine per cent were hospitalized because of concomitant bacterial infections and
      sepsis. Phylogenetic analysis of HIV isolates from case patients showed tight
      clustering suggesting a single common source of infection. The outbreak was
      temporally related to a widespread shift from heroin to injectable cathinone
      derivatives and buprenorphine, which entailed high-risk injection practices.
      Targeted intervention resulted in a dramatic and sustained reduction in HIV
      infection in the PWID population. CONCLUSIONS: Injectable amphetamines are
      gaining momentum among PWID worldwide. Tracing of this outbreak to cathinone use
      and implementing a targeted intervention programme effectively terminated the
      outbreak.

PMID- 27876591
TI  - Cystic Fibrosis and the Nervous System.
AB  - Cystic fibrosis (CF) is a life-shortening autosomal recessive disorder caused by
      mutations in the gene encoding the cystic fibrosis transmembrane conductance
      regulator (CFTR). CFTR is an anion channel that conducts bicarbonate and chloride
      across cell membranes. Although defective anion transport across epithelial cells
      is accepted as the basic defect in CF, many of the features observed in people
      with CF and organs affected by CF are modulated by the nervous system. This is of
      interest because CFTR expression has been reported in both the peripheral and
      central nervous systems, and it is well known that the transport of anions, such
      as chloride, greatly modulates neuronal excitability. Thus it is predicted that
      in CF, lack of CFTR in the nervous system affects neuronal function. Consistent
      with this prediction, several nervous system abnormalities and nervous system
      disorders have been described in people with CF and in animal models of CF. The
      goal of this special feature article is to highlight the expression and function
      of CFTR in the nervous system. Special emphasis is placed on nervous system
      abnormalities described in people with CF and in animal models of CF. Finally,
      features of CF that may be modulated by or attributed to faulty nervous system
      function are discussed.

PMID- 27876596
TI  - Characterization and immunomodulatory effects of glucans from Pleurotus albidus,
      a promising species of mushroom for farming and biomass production.
AB  - Polysaccharides from a number of mushroom species are recognized as functional
      food ingredients with potential health benefits, including immunomodulatory
      effects. In this study, polysaccharides extracted from the basidiome with cold
      water (BaCW), hot water (BaHW), and hot alkali (BaHA) solution, and exo- (MyEX)
      and endopolysaccharides (MyEN) from the submerged culture of Pleurotus albidus, a
      promising species for farming and biomass production, were analyzed for their
      chemical composition and structure and immunomodulatory effects on macrophages.
      Compositional (HPAEC-PAD and HPSEC-RID/MWD) and structural (FT-IR, 1D- and 2D
      NMR) analyses identified BaCW and MyEX as beta-(1,6)-branched beta-(1,3)-glucans,
      BaHW and MyEN as alpha-(1,3)-(1,2)-branched alpha-(1,6)-glucans, and BaHA as a
      mixture of alpha-(1,6)- and beta-(1,3)-glucans. BaCW and MyEX stimulated the
      production of tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO), but
      not interleukin-6 (IL-6), and decreased phagocytosis of zymosan particles. In
      contrast, BaHW and MyEN induced TNF-alpha, NO and IL-6 production, and increased
      zymosan phagocytosis, while BaHA displayed intermediary effects in comparison the
      other polysaccharides. In conclusion, the basidiome and the submerged culture of
      P. albidus are sources of easily extractable alpha- and beta-glucans with
      potential immunomodulatory effects.

PMID- 27876595
TI  - Behavioral, mental, and physical health characteristics and opioid medication
      misuse among community pharmacy patients: A latent class analysis.
AB  - BACKGROUND: Community pharmacists are well-positioned to address the US opioid
      medication crisis, which has created a need to detect misuse risk in order to
      provide optimal patient care. OBJECTIVES: This study sought to identify community
      pharmacy patient subgroups at risk for opioid medication misuse. METHODS: This
      study was a cross-sectional survey that examined behavioral, mental, and physical
      health characteristics among patients filling opioid pain medications. A
      convenience sample of adult patients filling opioid pain medications who were not
      receiving cancer treatment were screened in 2 urban and 2 rural community
      pharmacies in southwestern Pennsylvania. Patient subgroups were identified using
      latent class analysis. Latent class regression analysis was used to examine the
      association between subgroup membership and misuse. RESULTS: A total of 333
      patients completed the survey (response rate 71.4%). Latent class analysis
      results showed that a 3-class solution best fit the data, which were labeled:
      mental health (8.4%, n = 28), poor health (79.6%, n = 265), and hazardous alcohol
      use (12%, n = 40). Individuals within the mental health subgroup had an increased
      risk for opioid medication misuse (Odds Ratio = 6.23, 95% CI = 5.13-7.33).
      CONCLUSION: These findings demonstrate heterogeneity of this population receiving
      prescribed opioids and the potential to identify subgroups with high misuse risk.
      These findings also support routine screening of patients filling opioid
      medications and suggest the need for evidence-based patient-centered intervention
      development.

PMID- 27876597
TI  - Role of synbiotics in polysaccharide assisted colon targeted microspheres of
      mesalamine for the treatment of ulcerative colitis.
AB  - The present study explains the effect of concomitant administration of synbiotics
      with the polysaccharide based colon targeted delivery system. As the gut
      microflora get deranged on administration of mesalamine, drug release from such
      delivery systems is expected to be jeopardised because the release trigger is
      dependent solely on the colonic microbiota. To overcome this limitation,
      mesalamine was formulated as microspheres with guar gum and xanthan gum
      (prebiotics). These were combined with probiotics containing Lactobacillus
      acidophilus, L. rhamnosus, Bifidobacterium longumand Saccharomyces boulardi.
      Dissolution studies of the prepared formulation conducted in simulated colonic
      fluid clearly demonstrated its superiority over the marketed, delayed release
      dosage forms of mesalamine. The therapeutic benefit of the concomitant
      administration of synbiotic with mesalamine was evidenced by the comparative
      evaluation of faecal contents, weight gain trend and histopathological studies
      conducted in rats. The results suggest that co-administration of synbiotics with
      mesalamine can be used as a convenient methodology to achieve efficient and cost
      effective targeting of the drug to colon.

PMID- 27876598
TI  - Antithrombotic activity of Batroxase, a metalloprotease from Bothrops atrox
      venom, in a model of venous thrombosis.
AB  - BACKGROUND: Snake venoms are great sources of bioactive molecules, which may be
      used as models for new drugs. Toxins that interfere in hemostasis have received
      considerable attention over the years. OBJECTIVES: This study aimed at the
      evaluation of the antithrombotic activity of Batroxase, a P-I metalloprotease
      from Bothrops atrox venom, in an animal model of venous thrombosis. METHODS: The
      antithrombotic activity of Batroxase was tested in vivo in a model based on two
      factors of the Virchow's Triad: blood flow alterations (partial stenosis of the
      inferior vena cava), and vessel wall injury (10% ferric chloride for 5min), in
      comparison with sodium heparin (positive control) and saline (negative control).
      Bleeding/clotting time was assessed by a tail bleeding assay. The immunogenicity
      of Batroxase was also analyzed. RESULTS: Batroxase (12mg/kg) reduced thrombus
      formation in 81%, similarly to heparin (100U/kg), which reduced it in 85% in
      comparison with the saline group. Both Batroxase and heparin increased
      bleeding/clotting time in approximately 3 fold. Immunizations of rabbits with
      Batroxase do not result in detectable levels of antibodies against this
      metalloprotease. CONCLUSION: Batroxase presents antithrombotic activity in vivo.
      Moreover, its lack of immunogenicity increases the interest on its possible
      therapeutic potential over thrombogenic disorders.

PMID- 27876599
TI  - Self-emulsifying drug delivery systems (SEDDS): Proof-of-concept how to make them
      mucoadhesive.
AB  - AIM: The objective of this study was to provide a proof-of-concept that self
      emulsifying drug delivery systems can be made mucoadhesive by the incorporation
      of hydrophobic mucoadhesive polymers. METHODS: In order to obtain such a
      hydrophobic mucoadhesive polymer, Eudragit(r) S100 was thiolated by covalent
      attachment of cysteamine. After determination of the thiol group content, in
      vitro mucoadhesion studies (rotating cylinder and rheological measurements) were
      performed. Then, synthesized conjugate was incorporated into self-emulsifying
      drug delivery systems (SEDDS) and their toxic potential as well as that of
      unmodified and thiolated Eudragit(r) S100 was examined on Caco-2 cell line.
      Lastly, the mucoadhesiveness of developed SEDDS on porcine intestinal mucosa was
      determined. RESULTS: Generated thiolated Eudragit(r) S100 displaying 235+/
      14MUmol of free thiol groups and 878+/-101MUmol of disulfide bonds per gram
      polymer showed a great improvement in both: dynamic viscosity with mucus and
      adhesion time on mucosal tissue compared to the unmodified polymer. Resazurin
      assay revealed that unmodified and thiolated polymers and also SEDDS dispersions
      were non-toxic over Caco-2 cells. Furthermore, the incorporation of 1.5% (w/w) of
      such thiomer into SEDDS led to remarkably improved mucoadhesiveness. Blank SEDDS
      were completely removed from the mucosa within 15min, whereas >60% of SEDDS
      containing thiolated Eudragit(r) S100 were still attached to it. CONCLUSION:
      These results provide evidence that SEDDS can be made mucoadhesive by the
      incorporation of hydrophobic mucoadhesive polymers.

PMID- 27876600
TI  - Antimicrobial metabolites from the plant endophytic fungus Penicillium sp.
AB  - Five rare dichloro aromatic polyketides (1-5) were obtained from an endophytic
      fungus Penicillium sp., along with five known metabolites (6-10). Their
      structures were elucidated by extensive spectroscopic analysis, Mosher methods,
      as well as [Rh2(OCOCF3)4]-induced electronic circular dichroism (ECD)
      experiments. Compounds 2-4 and 6 structurally involved acyclic 1.3-diols, the
      uneasy configuration determinations of which were well carried out by double
      derivation NMR methods. Compounds 1-10 were evaluated for their antibacterial and
      antifungal activities against five strains of human pathogenic microorganisms.
      Helvolic acid (7) showed potent inhibitory effects against Staphylococcus aureus
      and Pseudomonas aeruginosa with MIC (minimum inhibitory concentration) values of
      5.8 and 4.6MUg/mL, respectively.

PMID- 27876601
TI  - Bioapplications of graphene constructed functional nanomaterials.
AB  - Graphene has distinctive mechanical, electronic, and optical properties, which
      researchers have applied to develop innovative electronic materials including
      transparent conductors and ultrafast transistors. Lately, the understanding of
      various chemical properties of graphene has expedited its application in high
      performance devices that generate and store energy. Graphene is now increasing
      its terrain outside electronic and chemical applications toward biomedical areas
      such as precise bio sensing through graphene-quenched fluorescence, graphene
      enhanced cell differentiation and growth, and graphene-assisted laser
      desorption/ionization for mass spectrometry. In this Account, we evaluate recent
      efforts to apply graphene and graphene oxides (GO) to biomedical research and a
      few different approaches to prepare graphene materials designed for biomedical
      applications and a brief perspective on their future applications. Because of its
      outstanding aqueous processability, amphiphilicity, surface functionalizability,
      surface enhanced Raman scattering (SERS), and fluorescence quenching ability, GO
      chemically exfoliated from oxidized graphite is considered a promising material
      for biological applications. In addition, the hydrophobicity and flexibility of
      large-area graphene synthesized by chemical vapor deposition (CVD) allow this
      material to play an important role in cell growth and differentiation. Graphene
      is considered to be an encouraging and smart candidate for numerous biomedical
      applications such as NIR-responsive cancer therapy and fluorescence bio-imaging
      and drug delivery. To that end, suitable preparation and unique approaches to
      utilize graphene-based materials such as graphene oxides (GOs), reduced graphene
      oxides (rGOs), and graphene quantum dots (GQDs) in biology and medical science
      are gaining growing interest.

PMID- 27876602
TI  - Genistein attenuates D-GalN induced liver fibrosis/chronic liver damage in rats
      by blocking the TGF-beta/Smad signaling pathways.
AB  - BACKGROUND AND AIM: Genistein is a major isoflavonoid abundantly found in soy.
      Earlier genistein has been reported to possess protective effect against a
      multitude of disorders including cancer. Previously we demonstrated the
      protective effects of Genistein in d-Galactosamine (D-GalN) induced fulminant
      hepatic failure (FHF) in rats. In present study, we evaluated the
      hepatoprotective activity of Genistein in rat model of chronic liver damage and
      liver fibrosis. METHODS: Liver fibrosis was induced by intraperitoneal injection
      of D-GalN (250 mg/kg BW) twice a week for 12 weeks. Genistein (5 mg/kg BW) was
      given via intra-gastric route as co-treatment daily for 12 weeks. RESULTS:
      Genistein co-treatment significantly attenuated D-GalN-induced chronic liver
      damage and liver fibrosis as evident from a significant amelioration in
      functional impairment, including inhibition of the activation of Hepatic stellate
      cells (HSC), decreased expression in alpha smooth muscle actin (alpha-SMA) and
      accumulation of collagen matrix, and an elevation in serum alanine transaminase
      (ALT) and aspartate transaminase (AST) level. In addition Genistein co-treatment
      was associated with elevated expression of hepatic Smad7, which ultimately blunts
      the expression of TGF-beta and the activation of TGF-beta/Smad signaling.
      Furthermore Genistein significantly prevented the histopathological changes
      induced by D-GalN. CONCLUSION: Our results suggest that Genistein could be a
      novel therapeutic/nutraceutical agent in treating chronic liver damage and liver
      fibrosis. In addition our study also suggests a possible mechanism of action in
      which Smad7-induced inhibition of TGF-beta/Smad2/3 can be a central mechanism by
      which Genistein protects liver from chronic injury.

PMID- 27876603
TI  - Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus
      Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable
      Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario
      Clinical Oncology Group (OCOG)-LUSTRE Trial.
AB  - We describe a Canadian phase III randomized controlled trial of stereotactic body
      radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for
      the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG
      LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT
      (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for
      centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of
      the study is 3-year local control, which we hypothesize will improve from 75%
      with CRT to 87.5% with SBRT. With 85% power to detect a difference of this
      magnitude (hazard ratio = 0.46), a 2-sided alpha = 0.05 and a 2:1 randomization,
      we require a sample size of 324 patients (216 SBRT, 108 CRT). Important secondary
      outcomes include overall survival, disease-free survival, toxicity, radiation
      related treatment death, quality of life, and cost-effectiveness. A robust
      radiation therapy quality assurance program has been established to assure
      consistent and high quality SBRT and CRT delivery. Despite widespread interest
      and adoption of SBRT, there still remains a concern regarding long-term control
      and risks of toxicity (particularly in patients with centrally located lesions).
      The OCOG-LUSTRE study is the only randomized phase III trial testing SBRT in a
      medically inoperable population, and the results of this trial will attempt to
      prove that the benefits of SBRT outweigh the potential risks.

PMID- 27876604
TI  - Predictors and Patterns of Regional Recurrence Following Lung SBRT: A Report From
      the Elekta Lung Research Group.
AB  - INTRODUCTION: The objective of this study was to determine the predictors and
      patterns of regional recurrence (RR) following stereotactic body radiotherapy
      (SBRT) for primary lung cancers. MATERIAL AND METHODS: Details of patient
      factors, treatment, and outcome factors were extracted from a multi-institutional
      (5) database. All events were calculated from the end of radiotherapy. Estimates
      of local recurrence, RR, and distant metastases (DM) were calculated using the
      competing risk method. Cause-specific and overall survival were calculated using
      the Kaplan-Meier method. Details of locations and number of simultaneous RRs were
      categorized by lymph node anatomic station. RESULTS: A total of 734 patients were
      analyzed. The median follow-up was 3.0 years in surviving patients. Four hundred
      seventy-six (65%) patients had pathologic proof of disease. There were 64
      patients with RR. The 2-year local recurrence, RR, and distant metastases rates
      were 5.6%, 9.0%, and 14.6% respectively. The 2-year cause-specific and overall
      survival were 89.9% and 63.7%, respectively. There were 136 simultaneous sites of
      RR. There were 21 recurrences in stations 4R (15.4%), 9 (6.6%) in 4L, 30 (22%) in
      7, 19 (13.9%) in 10R, and 14 (10.3%) in 10L. The most common stations for
      isolated recurrence (n = 19) were station 7 (n = 5; 26.3%) and station 10R (n =
      6; 31.6%). The most common RR levels were stations 4 and 7 for right and left
      upper lobe, stations 5, 7, and 10 for left lower lobe tumors, and stations 7 and
      10 for right lower lobe tumors. CONCLUSION: Stations 4, 7, and 10 were the most
      common stations for RR. These patterns of recurrence may guide nodal staging
      procedures prior to SBRT.

PMID- 27876606
TI  - Devastating Peristomal Pyoderma Gangrenosum: Challenges in Diagnosis and
      Management.

PMID- 27876605
TI  - Role of zebrafish NLRC5 in antiviral response and transcriptional regulation of
      MHC related genes.
AB  - Intracellular NOD-like receptors (NLRs) are emerging as critical regulators of
      innate and adaptive immune responses. Although the NLR family member NLRC5 is
      functionally defined, the role of NLRC5 in regulating innate immune signaling has
      been controversial in mammals, and is poorly understood in teleost fish. In the
      present study, we report the functional characterization of zebrafish NLRC5. The
      cloned NLRC5 consists of 6435 bp which encodes 1746 amino acids. The N-terminal
      effector-binding domain of zebrafish NLRC5 is absent which is different from all
      other human NLRs. Fluorescence microscopy showed that zebrafish NLRC5 is located
      throughout the entire cell. The higher expression of zebrafish NLRC5 in embryo
      than in larvae was observed, suggesting the action phase of NLRC5 in zebrafish
      ontogenetic stages. When the modulation of NLRC5 in pathogen infection was
      analyzed, it was found that zebrafish NLRC5 was upregulated by both bacterial and
      viral infection. Overexpression of zebrafish NLRC5 resulted in significant
      inhibition of SVCV replication in vivo and in vitro, but failed to activate
      interferon (IFN) promoters and type I IFN signaling pathway. Interestingly, NLRC5
      overexpression could activate mhc2dab promoter, and induce the expression of MHC
      class II genes. All together, these results demonstrate that zebrafish NLRC5 is
      involved in IFN-independent antiviral response, and also functions as a
      transcriptional regulator of MHC class II genes.

PMID- 27876607
TI  - An Unusual Case of Pain in the Gallbladder Area: Is It Acute Cholecystitis?

PMID- 27876608
TI  - The achievements of clinical chemistry testing: 1967-2017.

PMID- 27876609
TI  - Laboratory Medicine: Advances and challenges.

PMID- 27876610
TI  - Establishing reference intervals for hCG in postmenopausal women.
AB  - BACKGROUND: Plasma concentrations of human chorionic gonadotropin (hCG) have been
      shown to increase with age due to pituitary secretion. We previously recommended
      that an hCG cutoff of 14.0IU/L be used for women >=55years of age. However, it
      remains unknown whether concentrations >14.0IU/L can be expected in women with
      advanced age. Our objectives were to establish plasma hCG reference intervals and
      correlate follicle stimulating hormone (FSH) and hCG concentrations in
      postmenopausal females >=55years. METHODS: Residual plasma samples from 798 women
      >=55years were utilized with 303, 269, and 226 samples belonging to the age
      groups 55-69, 70-84, and >=85years, respectively. FSH and hCG were measured using
      the Abbott ARCHITECT. All positive hCG samples (hCG >=5IU/L) were analyzed for
      potential heterophile antibody interference and 3 were excluded. Electronic
      medical records were reviewed and patients with malignancy were excluded.
      RESULTS: 8% (56/666) of women age>=55years had plasma hCG >=5IU/L. There were 19,
      16, and 21 patients with hCG >=5IU/L in the age groups 55-69, 70-84, and
      >=85years, respectively. The highest hCG concentrations observed in each age
      group were: 55-69years maximum=11.7IU/L and 97.5th percentile=9.6IU/L; 70-84years
      maximum=18.09IU/L, 97.5th percentile=6.2IU/L; >=85years maximum=11.1IU/L and
      97.5th percentile=10.0IU/L, and the overall 97.5th percentile=8.5IU/L for all
      women >=55years of age. Neither hCG nor FSH concentrations continued to increase
      with age in women >=55years. CONCLUSIONS: The prevalence of positive hCG in women
      >=55years is 8%. This study confirms our previously recommended cutoff of 14IU/L
      for women >=55years of age. In women >=55years of age, FSH concentrations do not
      predict hCG concentrations.

PMID- 27876612
TI  - Lethal distemper in badgers (Meles meles) following epidemic in dogs and wolves.
AB  - Canine distemper virus (CDV) represents an important conservation threat to many
      wild carnivores. A large distemper epidemic sustained by an Arctic-lineage strain
      occurred in Italy in 2013, mainly in the Abruzzi region, causing overt disease in
      domestic and shepherd dogs, Apennine wolves (Canis lupus) and other wild
      carnivores. Two badgers were collected by the end of September 2015 in a rural
      area of the Abruzzi region and were demonstrated to be CDV-positive by real time
      RT-PCR and IHC in several tissues. The genome of CDV isolates from badgers showed
      Y549H substitution in the mature H protein. By employing all publicly available
      Arctic-lineage H protein encoding gene sequences, six amino acid changes in
      recent Italian strains with respect to Italian strains of dogs from 2000 to 2008,
      were observed. A CDV strain belonging to the European-wildlife lineage was also
      identified in a fox found dead in the same region in 2016, proving co-circulation
      of an additional CDV lineage.

PMID- 27876611
TI  - Re-emergence of amantadine-resistant variants among highly pathogenic avian
      influenza H5N1 viruses in Egypt.
AB  - Highly pathogenic avian influenza (HPAI) H5N1 virus continues to undergo
      substantial evolution. Emergence of antiviral resistance among H5N1 avian
      influenza viruses is a major challenge in the control of pandemic influenza.
      Numerous studies have focused on the genetic and evolutionary dynamics of the
      hemagglutinin and neuraminidase genes; however, studies on the susceptibility of
      HPAI H5N1 viruses to amantadine and genetic diversity of the matrix (M) gene are
      limited. Accordingly, we studied the amantadine susceptibility of the HPAI H5N1
      viruses isolated in Egypt during 2006-2015 based on genotypic and phenotypic
      characteristics. We analyzed data on 253 virus sequences and constructed a
      phylogenetic tree to calculate selective pressures on sites in the M2 gene
      associated with amantadine-resistance among different clades. Selection pressure
      was identified in the transmembrane domain of M2 gene at positions 27 and 31.
      Amantadine-resistant variants emerged in 2007 but were not circulating between
      2012 and 2014. By 2015, amantadine-resistant HPAI H5N1 viruses re-emerged. This
      may be associated with the uncontrolled prescription of amantadine for
      prophylaxis and control of avian influenza infections in the poultry farm sector
      in Egypt. More epidemiological research is required to verify this observation.

PMID- 27876613
TI  - Multiplex Amplification Refractory Mutation System PCR (ARMS-PCR) provides
      sequencing independent typing of canine parvovirus.
AB  - Canine parvovirus-2 antigenic variants (CPV-2a, CPV-2b and CPV-2c) ubiquitously
      distributed worldwide in canine population causes severe fatal gastroenteritis.
      Antigenic typing of CPV-2 remains a prime focus of research groups worldwide in
      understanding the disease epidemiology and virus evolution. The present study was
      thus envisioned to provide a simple sequencing independent, rapid, robust,
      specific, user-friendly technique for detecting and typing of presently
      circulating CPV-2 antigenic variants. ARMS-PCR strategy was employed using
      specific primers for CPV-2a, CPV-2b and CPV-2c to differentiate these antigenic
      types. ARMS-PCR was initially optimized with reference positive controls in two
      steps; where first reaction was used to differentiate CPV-2a from CPV-2b/CPV-2c.
      The second reaction was carried out with CPV-2c specific primers to confirm the
      presence of CPV-2c. Initial validation of the ARMS-PCR was carried out with 24
      sequenced samples and the results were matched with the sequencing results. ARMS
      PCR technique was further used to screen and type 90 suspected clinical samples.
      Randomly selected 15 suspected clinical samples that were typed with this
      technique were sequenced. The results of ARMS-PCR and the sequencing matched
      exactly with each other. The developed technique has a potential to become a
      sequencing independent method for simultaneous detection and typing of CPV-2
      antigenic variants in veterinary disease diagnostic laboratories globally.

PMID- 27876614
TI  - First molecular detection and genetic analysis of Anaplasma phagocytophilum in
      shelter cats in Seoul, Korea.
AB  - Here, we report the molecular detection of Anaplasma phagocytophilum in shelter
      cats in Korea and the relationships between A. phagocytophilum gene sequences and
      the pathogenicity, region, and host specificity of this bacterium. Two (0.9%) out
      of 222 shelter cats from Seoul, Korea, yielded positive results for the A.
      phagocytophilum 16S rRNA, groEL, and msp2 genes. Phylogenetic analysis divided
      groEL gene sequences into two groups (alanine and serine), based on their
      nucleotide and amino acid sequences. A. phagocytophilum msp2 gene sequences were
      grouped per the region of isolation (Europe vs. USA, including Korea). Some
      nucleotide and amino acid sequences of groEL and msp2 showed distinctive patterns
      according to the region of isolation, which helped in distinguishing A.
      phagocytophilum gene sequences detected in Korea from those detected in the USA
      and Europe. Although the limited number of clinical anaplasmosis cases caused by
      A. phagocytophilum belonging to the alanine group prevents any firm conclusions,
      the results of the present study tend to refute the previous view that the
      pathogenicity of A. phagocytophilum is associated with the serine group.
      Moreover, our results suggest that genetic analyses of groEL and msp2 can be used
      to obtain a regional fingerprint of A. phagocytophilum.

PMID- 27876615
TI  - A novel avian-like hepatitis E virus in wild aquatic bird, little egret (Egretta
      garzetta), in Hungary.
AB  - Hepatitis E virus (HEV), family Hepeviridae, has public health concerns because
      of its zoonotic potential; however, the host species spectrum, animal to animal
      transmissions, the natural chain of hepevirus infections and the genetic
      diversity of HEV in wildlife especially in birds are less known. Using random
      amplification and next generation sequencing technology a genetically divergent
      avian HEV was serendipitously identified in wild bird in Hungary. HEV RNA was
      detected with high faecal viral load (1.33*108genomiccopies/ml) measured by real
      time PCR in faecal sample from a little egret (Egretta garzetta). The complete
      genome of HEV strain little egret/kocsag02/2014/HUN (KX589065) is 6660-nt long
      including a 18-nt 5' end and a 103-nt 3' end (excluding the poly(A)-tail).
      Sequence analyses indicated that the ORF1 (4554nt/1517aa), ORF2 (1728nt/593aa)
      and ORF3 (339nt/112aa) encoded proteins of little egret/kocsag02/2014/HUN shared
      the highest identity (62.8%, 71% and 61.5%) to the corresponding proteins of
      genotype 1 avian (chicken) HEV in species Orthohepevirus B, respectively. This
      study reports the identification and complete genome characterization of a novel
      orthohepevirus distantly related to avian (chicken) HEVs at the first time in
      wild bird. It is important to recognize all potential hosts, reservoirs and
      spreaders in nature and to reconstruct the phylogenetic history of hepeviruses.
      Birds could be an important reservoir of HEV generally and could be infected with
      genetically highly divergent strains of HEV.

PMID- 27876617
TI  - Canagliflozin, a sodium glucose cotransporter 2 inhibitor, attenuates obesity
      induced inflammation in the nodose ganglion, hypothalamus, and skeletal muscle of
      mice.
AB  - Chronic inflammation in systemic organs, such as adipose tissue, nodose ganglion,
      hypothalamus, and skeletal muscles, is closely associated with obesity and
      diabetes mellitus. Because sodium glucose cotransporter 2 (SGLT2) inhibitors
      exert both anti-diabetic and anti-obesity effects by promoting urinary excretion
      of glucose and subsequent caloric loss, we investigated the effect of
      canagliflozin, an SGLT2 inhibitor, on obesity-induced inflammation in neural
      tissues and skeletal muscles of mice. High-fat diet (HFD)-fed male C57BL/6J mice
      were treated with canagliflozin for 8 weeks. Canagliflozin attenuated the HFD
      mediated increases in body weight, liver weight, and visceral and subcutaneous
      fat weight. Additionally, canagliflozin decreased blood glucose as well as the
      fat, triglyceride, and glycogen contents of the liver. Along with these metabolic
      corrections, canagliflozin attenuated the increases in the mRNA levels of the
      proinflammatory biomarkers Iba1 and Il6 and the number of macrophages/microglia
      in the nodose ganglion and hypothalamus. In the skeletal muscle of HFD-fed obese
      mice, canagliflozin decreased inflammatory cytokine levels, macrophage
      accumulation, and the mRNA level of the specific atrophic factor atrogin-1.
      Canagliflozin also increased the mRNA level of insulin-like growth factor 1,
      protected against muscle mass loss, and restored the contractile force of muscle.
      These findings suggested that SGLT2 inhibition disrupts the vicious cycle of
      obesity and inflammation, not only by promoting caloric loss, but also by
      suppression of obesity-related inflammation in both the nervous system and
      skeletal muscle.

PMID- 27876618
TI  - TLR4/NF-kappaB/Ceramide signaling contributes to Ox-LDL-induced calcification of
      human vascular smooth muscle cells.
AB  - Vascular calcification is a major feature of advanced atherosclerosis and highly
      associated with cardiovascular diseases. Oxidized low density lipoprotein (Ox
      LDL) has been recognized as a critical risk factor for atherosclerosis and
      osteogenic differentiation of vascular smooth muscle cells (VSMCs). Previous
      studies have demonstrated that toll like receptor 4 (TLR4) is highly expressed in
      atherosclerotic lesions and participates in the progression of atherosclerosis.
      However, the role of TLR4 in vascular calcification remains unknown. In this
      study, we investigated whether TLR4 modulates vascular calcification induced by
      Ox-LDL. TLR4 expression was up-regulated in cultured human VSMCs treated with Ox
      LDL. Knockdown of TLR4 by small interfering RNA (siRNA) significantly reduced Ox
      LDL-induced calcification, detected by alizarin red staining and calcium content
      assay. TLR4 siRNA also decreased the mRNA expression of bone-related proteins
      including Msx2, osterix, BMP2 and KLF4, but increased the expression of VSMC
      contractile proteins including SMA and SM22alpha in VSMCs. In addition, Ox-LDL
      stimulated nuclear translocation of nuclear factor kappa B (NK-kappaB) p65. These
      effects of Ox-LDL on VSMCs were reversed by TLR4 siRNA. Furthermore, NK-kappaB
      inhibitor, pyrrolidine dithiocarbamate (PDTC), attenuated Ox-LDL-induced VSMC
      calcification, which was rescued by C2-ceramide treatment. In conclusion, these
      findings suggest that TLR4 regulates VSMC calcification induced by Ox-LDL through
      activation of NK-kappaB, highlighting the critical role of TLR4/NK-kappaB
      signaling in vascular calcification.

PMID- 27876616
TI  - The Starting Treatment for Ethanol in Primary care Trials (STEP Trials): Protocol
      for Three Parallel Multi-Site Stepped Care Effectiveness Studies for Unhealthy
      Alcohol Use in HIV-Positive Patients.
AB  - Unhealthy alcohol use is common among HIV-positive patients, yet effective
      evidence-based treatments are rarely provided in clinical settings providing HIV
      care. Further, given patient variability in response to initial treatments,
      stepped care approaches may be beneficial. We describe the rationale, aims and
      study design for the current StartingTreatment forEthanol inPrimary care Trials
      (STEP Trials); three parallel randomized controlled effectiveness trials being
      conducted in five Infectious Disease Clinics. Participants meeting criteria for:
      1) at-risk drinking, 2) moderate alcohol use with liver disease (MALD), or 3)
      alcohol use disorder (AUD) are randomized to integrated stepped care versus
      treatment as usual. For those with at-risk drinking or MALD, integrated stepped
      care starts with a one session brief intervention and follow-up 2-week telephone
      booster. Based on pre-specified nonresponse criteria, participants may be
      "stepped up" at week 4 to receive four sessions of motivational enhancement
      therapy (MET) and "stepped up" again at week 12 for addiction physician
      management (APM) and consideration of alcohol pharmacotherapy. For those with
      AUD, integrated stepped care begins with APM. Non-responders may be "stepped up"
      at week 4 to receive MET and again at week 12 for a higher level of care (e.g.
      intensive outpatient program). The primary outcome is alcohol consumption
      assessed at 24weeks, and secondary outcome is the VACS Index, a validated measure
      of HIV morbidity and mortality risk. Results from the STEP Trials should inform
      future research and the implementation of interventions to address unhealthy
      alcohol use among HIV-positive individuals.

PMID- 27876620
TI  - The GABAB positive allosteric modulators CGP7930 and GS39783 stimulate ERK1/2
      signalling in cells lacking functional GABAB receptors.
AB  - The present study shows that the GABAB positive allosteric modulators (PAMs)
      CGP7930 and GS39783 stimulate extracellular signal-regulated protein kinases 1
      and 2 (ERK1/2) signalling in cells that do not express functional GABAB
      receptors. In human SH-SY5Y neuroblastoma cells, CGP7930 and GS39783 induced a
      time- and concentration-dependent increase in ERK1/2 phosphorylation with
      potencies similar to those displayed as GABAB PAMs. Conversely, gamma
      aminobutyric acid and the GABAB receptor agonists (-)baclofen and SKF97541 were
      completely inactive. CGP7930 and GS39783 enhanced the nuclear localization of
      phospho-ERK1/2 and CGP7930 promoted the phosphorylation of the transcription
      factors Elk-1 and CREB. CGP7930-induced ERK1/2 stimulation was insensitive to
      pertussis toxin, the Gq/11 antagonist YM254890 and the phospholipase C-beta
      inhibitor U-73122, but was completely blocked by the MEK1/2 inhibitor PD98059.
      Inhibition of insulin-like growth factor-1, platelet--derived growth factor,
      phosphoinositide 3-kinase and Akt activities potentiated CGP7930-induced ERK1/2
      phosphorylation. CGP7930 enhanced the phosphorylation of myristoylated alanine
      rich protein kinase C (PKC) substrate and inhibition of PKC attenuated the ERK1/2
      stimulation. Over-expression of N17Ras, a dominant negative mutant of c-Ras, or
      inhibition of c-Raf by GW5074 partially antagonized CGP7930-induced ERK1/2
      activation. CGP7930 enhanced the phosphorylation of transforming growth factor
      beta-activated kinase 1 (TAK-1) and TAK-1 inhibition by 5Z-7-oxozeaenol reduced
      CGP7930-induced ERK1/2 phosphorylation. CGP7930 activated ERK1/2 in CHO-K1
      fibroblasts, which lack endogenous GABAB receptors, but not in HEK-293 cells,
      indicating that the response displayed cell type specificity. These data
      demonstrate that CGP7930 and GS39783 can trigger ERK1/2 signalling, a critical
      modulator of mood and drug addiction, independently of an action on GABAB
      receptors.

PMID- 27876621
TI  - Translational resistivity/conductivity of coding sequences during exponential
      growth of Escherichia coli.
AB  - Codon adaptation index (CAI) has been widely used for prediction of expression of
      recombinant genes in Escherichia coli and other organisms. However, CAI has no
      mechanistic basis that rationalizes its application to estimation of
      translational efficiency. Here, I propose a model based on which we could
      consider how codon usage is related to the level of expression during exponential
      growth of bacteria. In this model, translation of a gene is considered as an
      analog of electric current, and an analog of electric resistance corresponding to
      each gene is considered. "Translational resistance" is dependent on the steady
      state concentration and the sequence of the mRNA species, and "translational
      resistivity" is dependent only on the mRNA sequence. The latter is the sum of two
      parts: one is the resistivity for the elongation reaction (coding sequence
      resistivity), and the other comes from all of the other steps of the decoding
      reaction. This electric circuit model clearly shows that some conditions should
      be met for codon composition of a coding sequence to correlate well with its
      expression level. On the other hand, I calculated relative frequency of each of
      the 61 sense codon triplets translated during exponential growth of E. coli from
      a proteomic dataset covering over 2600 proteins. A tentative method for
      estimating relative coding sequence resistivity based on the data is presented.

PMID- 27876619
TI  - Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile
      allodynia in rats with peripheral nerve injury.
AB  - Neuropathic pain is a debilitating, chronic condition with a significant unmet
      need for effective treatment options. Recent studies have demonstrated that in
      addition to neurons, non-neuronal cells such as microglia contribute to the
      initiation and maintenance of allodynia in rodent models of neuropathic pain. The
      Ca2+- activated K+ channel, KCa3.1 is critical for the activation of immune
      cells, including the CNS-resident microglia. In order to evaluate the role of
      KCa3.1 in the maintenance of mechanical allodynia following peripheral nerve
      injury, we used senicapoc, a stable and highly potent KCa3.1 inhibitor. In
      primary cultured microglia, senicapoc inhibited microglial nitric oxide and IL
      1beta release. In vivo, senicapoc showed high CNS penetrance and when
      administered to rats with peripheral nerve injury, it significantly reversed
      tactile allodynia similar to the standard of care, gabapentin. In contrast to
      gabapentin, senicapoc achieved efficacy without any overt impact on locomotor
      activity. Together, the data demonstrate that the KCa3.1 inhibitor senicapoc is
      effective at reducing mechanical hypersensitivity in a rodent model of peripheral
      nerve injury.

PMID- 27876622
TI  - A novel C-type lectin in the black tiger shrimp Penaeus monodon functions as a
      pattern recognition receptor by binding and causing bacterial agglutination.
AB  - C-type lectins are pattern recognition proteins that play important roles in
      innate immunity in invertebrates by mediating the recognition of pathogens. In
      this study, a novel C-type lectin gene, PmCLec, was cloned and characterized from
      the black tiger shrimp Penaeus monodon. The open reading frame of PmCLec is 657
      bp in length. It encodes a predicted protein of 218 amino acids with a calculated
      molecular mass and an isoelectric point of 24086 Da and 4.67, respectively.
      Sequence analysis of PmCLec showed similarity to members of the C-type lectin
      gene superfamily. The deduced protein contains a single carbohydrate recognition
      domain (CRD) and four conserved cysteine residues (Cys58, Cys126, Cys141, Cys149)
      that are involved in the formation of disulfide bridges. PmCLec transcripts are
      expressed in various tiger shrimp tissues, with the highest expression in the
      lymphoid organ. RNAi-mediated silencing of PmCLec resulted in higher cumulative
      mortality of knockdown shrimp after Vibrio harveyi infection compared to the
      control groups. Recombinant PmCLec was successfully expressed in the E. coli
      system. In the presence of Ca2+, purified rPmCLec protein binds and agglutinates
      Gram-positive bacteria (Staphylococcus aureus, S. hemolyticus), but only slightly
      binds and agglutinates E. coli and could not bind to the Gram-negative bacteria
      Bacillus megaterium and Vibrio harveyi. These results suggest that PmCLec
      functions as a pattern recognition receptor that is implicated in shrimp innate
      immunity.

PMID- 27876623
TI  - Identification of sea perch (Lateolabrax japonicus) ribonucleoprotein PTB-Binding
      1 involved in antiviral immune response against RGNNV.
AB  - RIG-I-like receptors (RLRs) can recognize viral RNA and initiate innate antiviral
      response. In earlier studies, we demonstrated that RLRs were implicated in the
      antiviral immunity against RGNNV in the seawater fish sea perch (Lateolabrax
      japonicus). However, potential regulators of RLRs-mediated signaling pathways
      involved in RGNNV infection remain unclear. In this study, a novel
      ribonucleoprotein PTB-binding 1 (Raver1) of sea perch (LjRAVER1) was identified
      for the first time. The cDNA of LjRAVER1 was 4066 bp in length and encoded a
      deduced polypeptide of 733 amino acids. Phylogenetic analysis revealed a closer
      affinity of LjRAVER1 with Larimichthys Crocea Raver1. LjRAVER1 mRNA was
      constitutively expressed in all 10 sampled tissues, and rapidly and significantly
      increased in vivo upon RGNNV infection. Time course analysis showed that LjRAVER1
      transcripts were significantly increased both in vivo and in vitro after RGNNV
      infection. Viral infection and poly I:C treatment caused translocation of
      LjRAVER1 from the nucleus to the cytoplasm. Ectopic expression of LjRAVER1
      increased the transcription level of several RLR signaling pathway related genes
      inducible by poly I:C treatment in vitro. Moreover, the viral gene transcription
      and virus production of RGNNV were significantly decreased in LjRAVER1
      overexpressing cells. Luciferase reporter assays demonstrated that overexpression
      of LjRAVER1 significantly increased the promoter activity of zebrafish IFN1.
      Taken together, these findings indicated that LjRAVER1 might be an important
      component of RLR signaling pathway and involved in RLR pathway-mediated IFN
      response in sea perch.

PMID- 27876624
TI  - Differences in structure and changes in gene regulation of murrel molecular
      chaperone HSP family during epizootic ulcerative syndrome (EUS) infection.
AB  - Heat shock proteins (HSPs) are immunogenic, ubiquitous class of molecular
      chaperones, which are induced in response to various environmental and microbial
      stressful conditions. It plays a vital role in maintaining cellular protein
      homeostasis in eukaryotic cells. In this study, we described a comprehensive
      comparative data by bioinformatics approach on three different full length cDNA
      sequences of HSP family at molecular level. The cDNA sequences of three HSPs were
      identified from constructed cDNA library of Channa striatus and named as CsCPN60,
      CsHSP60 and CsHSP70. We have conducted various physicochemical study, which
      showed that CsHSP70 (666 amino acid) possessed a larger polypeptides followed by
      CsCPN60 (575) and CsCPN60 (542). Three dimensional structural analysis of these
      HSPs showed maximum residues in alpha-helices and least in beta-sheets; also
      CsHSP60 lacks beta-sheet and formed helix-turn-helix structure. Further analysis
      indicated that each HSP carried distinct domains and gene specific signature
      motif, which showed that each HSP are structurally diverse. Homology and
      phylogenetic study showed that the sequences taken for analysis shared maximum
      identity with fish HSP family. Tissue specific mRNA expression analysis revealed
      that all the HSPs showed maximum expression in one of the major immune organ such
      as CsCPN60 in kidney, CsHSP60 in spleen and CsHSP70 in head kidney. To understand
      the function of HSPs in murrel immune system, the elevation in mRNA expression
      level was analyzed against microbial oxidative stressors such as fungal
      (Aphanomyces invadans) and bacterial (Aeromonas hydrophila). It is interesting to
      note that all the HSP showed a different expression pattern and reached maximum
      up-regulation at 48 h post-infection (p.i) during fungal stress, whereas in
      bacterial stress only CsCPN60 showed maximum up-regulation at 48 h p.i, but
      CsHSP60 and CsHSP70 showed maximum up-regulation at 24 h p.i. The differential
      expression pattern showed that each HSP is diverse in function. Overall, the
      elevation in expression levels showed that HSPs might have potential involvement
      in murrel immune protection thus, protecting the organism against various
      external stimuli including environmental and microbial stress.

PMID- 27876625
TI  - Deep sequencing for discovery and evolutionary analysis of plant viruses.
AB  - The advent of next generation sequencing (NGS), or deep sequencing, has allowed
      great advances to be made in discovery, diagnostics, and evolutionary studies in
      plant viruses. Various methods have been used for enrichment for virus-specific
      nucleic acids, each of which have some drawbacks. Many novel viruses have been
      discovered in plants by NGS technologies, and there is a good deal of promise for
      more comprehensive studies in virus evolution. However, each aspect of using NGS
      has its caveats that need to be considered, and there is still a need for better
      tools of analysis, as well as method for validation of sequence variation.

PMID- 27876626
TI  - Life-threatening NLRC4-associated hyperinflammation successfully treated with IL
      18 inhibition.

PMID- 27876627
TI  - IL-33 fine tunes mast cell degranulation and chemokine production at the single
      cell level.
AB  - BACKGROUND: Mast cells are versatile key components of allergy and inflammation
      known to respond to both innate and adaptive immunologic stimuli. However, the
      response of individual mast cells to cumulative stimuli remains poorly
      understood. OBJECTIVES: We sought to dissect mast cell responses at the single
      cell level and their potentiation by IL-33. METHODS: We monitored mast cell
      degranulation in real time by exploiting the capacity of fluorochrome-labeled
      avidin to stain degranulating cells. During the degranulation process, the
      granule matrix is externalized and immediately bound by fluorochrome-labeled
      avidin present in the culture medium. The degranulation process is monitored by
      using either time-lapse microscopy or fluorescence-activated cell sorting
      analysis. RESULTS: Single-cell analysis revealed a strong heterogeneity of
      individual mast cell degranulation responses. We observed that the number of
      degranulating mast cells was graded according to the FcepsilonRI stimulation
      strength, whereas the magnitude of individual mast cell degranulation remained
      unchanged, suggesting an all-or-none response of mast cells after FcepsilonRI
      triggering. IL-33 pretreatment increased not only the number of degranulating and
      chemokine-producing mast cells but also the magnitude of individual mast cell
      degranulation and chemokine production. CONCLUSION: We illustrate the effect of
      IL-33 on mast cell biology at the single-cell level by showing that IL-33
      potentiates IgE-mediated mast cell responses by both increasing the number of
      responding cells and enhancing the responses of individual mast cells.

PMID- 27876629
TI  - Improvement of idiopathic membranous nephropathy diagnosis with ultrasensitive
      quantitative detection of anti-phospholipase A2 receptor.

PMID- 27876628
TI  - Blocking antibodies induced by immunization with a hypoallergenic parvalbumin
      mutant reduce allergic symptoms in a mouse model of fish allergy.
AB  - BACKGROUND: Fish is a frequent elicitor of severe IgE-mediated allergic
      reactions. Beside avoidance, there is currently no allergen-specific therapy
      available. Hypoallergenic variants of the major fish allergen, parvalbumin, for
      specific immunotherapy based on mutation of the 2 calcium-binding sites have been
      developed. OBJECTIVES: This study sought to establish a mouse model of fish
      allergy resembling human disease and to investigate whether mouse and rabbit IgG
      antibodies induced by immunization with a hypoallergenic mutant of the major carp
      allergen protect against allergic symptoms in sensitized mice. METHODS: C3H/HeJ
      mice were sensitized with recombinant wildtype Cyp c 1 or carp extract by
      intragastric gavage. Antibody, cellular immune responses, and epitope specificity
      in sensitized mice were investigated by ELISA, rat basophil leukemia assay, T
      cell proliferation experiments using recombinant wildtype Cyp c 1, and
      overlapping peptides spanning the Cyp c 1 sequence. Anti-hypoallergenic Cyp c 1
      mutant mouse and rabbit sera were tested for their ability to inhibit IgE
      recognition of Cyp c 1, Cyp c 1-specific basophil degranulation, and Cyp c 1
      induced allergic symptoms in the mouse model. RESULTS: A mouse model of fish
      allergy mimicking human disease regarding IgE epitope recognition and symptoms as
      close as possible was established. Administration of antisera generated in mice
      and rabbits by immunization with a hypoallergenic Cyp c 1 mutant inhibited IgE
      binding to Cyp c 1, Cyp c 1-induced basophil degranulation, and allergic symptoms
      caused by allergen challenge in sensitized mice. CONCLUSIONS: Antibodies induced
      by immunization with a hypoallergenic Cyp c 1 mutant protect against allergic
      reactions in a murine model of fish allergy.

PMID- 27876631
TI  - Cumbersome removal of a lumen-apposing metal stent in a case of refractory
      pancreatic pseudocyst.

PMID- 27876630
TI  - Disruptions of the genes involved in lysine biosynthesis, iron acquisition, and
      secondary metabolisms affect virulence and fitness in Metarhizium robertsii.
AB  - Based on genomic analysis, polyketide synthase (PKS) and nonribosomal peptide
      synthetase (NRPS) pathways account for biosynthesis of the majority of the
      secondary metabolites produced by the entomopathogenic fungus Metarhizium
      robertsii. To evaluate the contribution of these pathways to M. robertsii fitness
      and/or virulence, mutants deleted for mrpptA, the Sfp-type 4' phosphopantetheinyl
      transferase gene required for their activation were generated. DeltamrpptA
      strains were deficient in PKS and NRPS activity resulting in colonies that lacked
      the typical green pigment and failed to produce the nonribosomal peptides
      (destruxins, serinocylins, and the siderophores ferricrocin and metachelins) as
      well as the hybrid polyketide-peptides (NG-39x) that are all produced by the wild
      type (WT) M. robertsii. The DeltamrpptA colonies were also auxotrophic for
      lysine. Two other mutant strains were generated: DeltamraarA, in which the alpha
      aminoadipate reductase gene critical for lysine biosynthesis was disrupted, and
      DeltamrsidA, in which the L-ornithine N5-oxygenase gene that is critical for
      hydroxamate siderophore biosynthesis was disrupted. The phenotypes of these
      mutants were compared to those of DeltamrpptA to separate effects of the loss of
      lysine or siderophore production from the overall effect of losing all polyketide
      and non-ribosomal peptide production. Loss of lysine biosynthesis marginally
      increased resistance to H2O2 while it had little effect on the sensitivity to the
      cell wall disruptor sodium dodecyl sulfate (SDS) and no effect on sensitivity to
      iron deprivation. In contrast, combined loss of metachelin and ferricrocin
      through the inactivation of mrsidA resulted in mutants that were as
      hypersensitive or slightly more sensitive to H2O2, iron deprivation, and SDS, and
      were either identical or marginally higher in DeltamrpptA strains. In contrast to
      DeltamrpptA, loss of mrsidA did not completely abolish siderophore activity,
      which suggests the production of one or more non-hydroxamate iron-chelating
      compounds. Deletion of mrpptA, mrsidA, and mraarA reduced conidium production and
      conidia of a GFP-tagged DeltamrpptA strain displayed a longer germination delay
      than WT on insect cuticles, a deficiency that was rescued by lysine
      supplementation. Compared with WT, DeltamrpptA strains displayed ~19-fold
      reduction in virulence against Drosophila suzukii. In contrast, lysine auxotrophy
      and loss of siderophores accounted for ~2 and ~6-fold decreases in virulence,
      respectively. Deletion of mrpptA had no significant effect on growth inhibition
      of Bacillus cereus. Our results suggest that PKS and NRPS metabolism plays a
      significant role in M. robertsii virulence, depresses conidium production, and
      contributes marginally to resistance to oxidative stress and iron homeostasis,
      but has no significant antibacterial effect.

PMID- 27876632
TI  - Severe acute diverticular bleeding: successful treatment with hemostatic powder.

PMID- 27876633
TI  - Classification of nuclear morphology in endocytoscopy of colorectal neoplasms.
AB  - BACKGROUND AND AIMS: We investigated endocytoscopy (EC) findings that were
      considered risk factors for colorectal neoplasms and determined whether they
      could be used as new indices to identify carcinomas with massive submucosal
      invasion (SM-m) or worse outcomes. METHODS: We performed a multivariate analysis
      of 8 factors on EC images to determine whether they were associated with SM-m or
      worse. Based on the results, we divided the EC3a category of the EC
      classification into low grade or high grade and investigated the diagnostic
      accuracy of this subclassification. In addition, we compared the diagnostic
      ability of EC for SM-m with that of other modalities (narrow-band imaging and pit
      pattern). RESULTS: The multivariate analysis indicated that unclear glandular
      lumens (ULs), high degree of nuclear enlargement (HNE), and multilayered nuclei
      (MNs) were the most useful factors for the diagnosis of SM-m or worse. The odds
      ratios for these factors were 12.47, 12.29, and 10.48, respectively (P < .001).
      The sensitivity, specificity, positive predictive value, negative predictive
      value, accuracy, and positive likelihood ratio for the diagnostic accuracy of the
      EC3a subclassification were 88.9%, 91.3%, 75.0%, 96.6%, 90.8%, and 10.2,
      respectively (P < .001). The sensitivity, negative predictive value, and accuracy
      of EC were significantly higher than those of narrow-band imaging and pit
      pattern. CONCLUSIONS: From the EC findings, the presence of ULs, HNE, and MNs are
      important risk factors for SM-m or worse outcomes. Furthermore, the EC3a
      subclassification taking these findings into consideration could be effective for
      the diagnosis of SM-m or worse. (Clinical trial registration number: UMIN
      000014906.).

PMID- 27876634
TI  - Individual and interactive sex-specific effects of acute restraint and systemic
      IFN-gamma treatment on neurochemistry.
AB  - Compelling evidence supports the involvement of the pro-inflammatory cytokines,
      IL-6, IFN-alpha and TNF-alpha in depression and related stress-associated
      pathologies. A role has also been suggested for the Th1-type cytokine, IFN-gamma,
      with most mechanistic accounts focusing on the cytokine's capacity to induce
      indoleamine 2,3-dioxygenase (IDO), leading to diminished tryptophan and the
      generation of kynurenine metabolites. Beyond these IDO-dependent routes, there is
      surprisingly little evidence directly linking IFN-gamma to alterations of brain
      regional monoamine activity and HPA axis functioning. Our specific aims in the
      present study were twofold: 1) assess the behavioural, plasma corticosterone and
      brain regional monoamine effects of acute systemic IFN-gamma, with or without
      short duration restraint stress (15 min), and 2) determine the sex-specific
      nature of these effects. As predicted, IFN-gamma stimulated monoaminergic
      activity within a number of stressor-sensitive limbic brain regions, most notably
      the paraventricular nucleus of the hypothalamus, central amygdala and prefrontal
      cortex. While several of these effects were sex-specific, there was little in the
      way of synergism between the cytokine and stressor treatments. Nonetheless, IFN
      gamma did synergistically interact with acute restraint stress to increase plasma
      corticosterone concentrations, and this effect was most pronounced in the male
      mice. These data are among the first to show that systemically administered IFN
      gamma can alone or in conjunction with psychologically relevant stressor, modify
      brain regional monoamine activity and the plasma corticosterone response.

PMID- 27876635
TI  - Creating Humanistic Clinicians Through Palliative Care Education.

PMID- 27876636
TI  - Concordance Between Veterans' Self-Report and Documentation of Surrogate Decision
      Makers: Implications for Quality Measurement.
AB  - CONTEXT: The Measuring What Matters initiative of the American Academy of Hospice
      and Palliative Medicine and the Hospice and Palliative Nurses Association
      identified documentation of a surrogate decision maker as one of the top 10
      quality indicators in the acute hospital and hospice settings. OBJECTIVES: To
      better understand the potential implementation of this Measuring What Matters
      quality measure #8, Documentation of Surrogate in outpatient primary care
      settings by describing primary care patients' self-reported identification and
      documentation of a surrogate decision maker. METHODS: Examination of patient
      responses to self-assessment questions from advance health care planning
      educational groups conducted in one medical center primary care clinic and seven
      community-based outpatient primary care clinics. We assessed the concordance
      between patient reports of identifying and naming a surrogate decision maker and
      having completed an advance directive (AD) with presence of an AD in the
      electronic medical record. RESULTS: Of veterans without a documented AD on file,
      more than half (66%) reported that they had talked with someone they trusted and
      nearly half (52%) reported that they had named someone to communicate their
      preferences. CONCLUSIONS: Our clinical project data suggest that many more
      veterans may have initiated communications with surrogate decision makers than is
      evident in the electronic medical record. System changes are needed to close the
      gap between veterans' plans for a surrogate decision maker and the documentation
      available to acute care health care providers.

PMID- 27876638
TI  - Changes in acoustic startle reflex in rats induced by playback of 22-kHz calls.
AB  - In aversive or dangerous situations, adult rats emit long characteristic
      ultrasonic calls, often termed "22-kHz calls," which have been suggested to play
      a role of alarm calls. Although the playback experiment is one of the most
      effective ways to investigate the alarming properties of 22-kHz calls, clear
      behavioral evidence showing the anxiogenic effects of these playback stimuli has
      not been directly obtained to date. In this study, we investigated whether
      playback of 22-kHz calls or synthesized sine tones could change the acoustic
      startle reflex (ASR), enhancement of which is widely considered to be a reliable
      index of anxiety-related negative affective states in rats. Playback of 22-kHz
      calls significantly enhanced the ASR in rats. Enhancement effects caused by
      playback of 22-kHz calls from young rats were relatively weak compared to those
      after calls from adult rats. Playback of synthesized 25-kHz sine tones enhanced
      ASR in subjects, but not synthesized 60-kHz tones. Further, shortening the
      individual call duration of synthesized 25-kHz sine tones also enhanced the ASR.
      Accordingly, it is suggested that 22-kHz calls induce anxiety by socially
      communicated alarming signals in rats. The results also demonstrated that call
      frequency, i.e., of 22kHz, appears important for ultrasonic alarm-signal
      communication in rats.

PMID- 27876637
TI  - Fourth ventricle injection of ghrelin decreases angiotensin II-induced fluid
      intake and neuronal activation in the paraventricular nucleus of the
      hypothalamus.
AB  - Ghrelin acts in the CNS to decrease fluid intake under a variety of dipsogenic
      and natriorexigenic conditions. Previous studies on this topic, however, focused
      on the forebrain as a site of action for this effect of ghrelin. Because the
      hindbrain contains neural substrates that are capable of mediating the well
      established orexigenic effects of ghrelin, the current study tested the
      hypothesis that ghrelin applied to the hindbrain also would affect fluid intake.
      To this end, water and saline intakes were stimulated by central injection of
      angiotensin II (AngII) in rats that also received injections of ghrelin
      (0.5MUg/MUl) into either the lateral or fourth ventricle. Ghrelin injected into
      either ventricle reduced both water and 1.8% NaCl intake that was stimulated by
      AngII. The nature of the intake effect revealed some differences between the
      injection sites. For example, forebrain application of ghrelin reduced saline
      intake by a reduction in both the number of licking bursts and the size of each
      licking burst, but hindbrain application of ghrelin had a more selective effect
      on burst number. In an attempt to elucidate a brain structure in which hindbrain
      administered ghrelin and forebrain-administered AngII interact to cause the
      ingestive response, we used Fos-immunohistochemistry in rats given the treatments
      used in the behavioral experiments. Although several brain areas were found to
      respond to either ghrelin or AngII, of the sites examined, only the
      paraventricular nucleus of the hypothalamus (PVN) emerged as a potential site of
      interaction. Specifically, AngII treatment caused expression of Fos in the PVN
      that was attenuated by concomitant treatment with ghrelin. These experiments
      provide the novel finding that the hindbrain contains elements that can respond
      to ghrelin and cause decreases in AngII-induced fluid intake, and that direct
      actions by ghrelin on forebrain structures is not necessary. Moreover, these
      studies suggest that the PVN is an important site of interaction between these
      two peptides.

PMID- 27876639
TI  - Behavioral changes in male mice fed a high-fat diet are associated with IL-1beta
      expression in specific brain regions.
AB  - High-fat diet (HFD)-induced obesity is associated with not only increased risk of
      metabolic and cardiovascular diseases, but cognitive deficit, depression and
      anxiety disorders. Obesity also leads to low-grade peripheral inflammation, which
      plays a major role in the development of metabolic alterations. Previous studies
      suggest that obesity-associated central inflammation may underlie the development
      of neuropsychiatric deficits, but further research is needed to clarify this
      relationship. We used 48 male C57BL/6J mice to investigate whether chronic
      consumption of a high-fat diet leads to increased expression of interleukin-1beta
      (IL-1beta) in the hippocampus, amygdala and frontal cortex. We also determined
      whether IL-1beta expression in those brain regions correlates with changes in the
      Y-maze, open field, elevated zero maze and forced swim tests. After 16weeks on
      dietary treatments, HFD mice showed cognitive impairment on the Y-maze test,
      greater anxiety-like behavior during the open field and elevated zero maze tests,
      and increased depressive-like behavior in the forced swim test. Hippocampal and
      amygdalar expression of IL-1beta were significantly higher in HFD mice than in
      control mice fed a standard diet (SD). Additionally, hippocampal GFAP and Iba1
      immunoreactivity were increased in HFD mice when compared to SD controls.
      Cognitive performance negatively correlated with level of IL-1beta in the
      hippocampus and amygdala whereas an observed increase in anxiety-like behavior
      was positively correlated with higher expression of IL-1beta in the amygdala.
      However, we observed no association between depressive-like behavior and IL-1beta
      expression in any of the brain regions investigated. Together our data provide
      evidence that mice fed a HFD exhibit cognitive deficits, anxiety and depressive
      like behaviors. Our results also suggest that increased expression of IL-1beta in
      the hippocampus and amygdala may be associated with the development of cognitive
      deficits and anxiety-like behavior, respectively.

PMID- 27876641
TI  - Individual differences in personality in laying hens are related to learning a
      colour cue association.
AB  - Personality can influence how animals perceive and learn cues. The behaviour and
      physiological responses animals show during stressful events is indicative of
      their personality. Acute induced stress prior to a cognitive test are known to
      affect the judgement of a stimulus, but personality of an individual could also
      affect learning of a specific cognitive paradigm. Here, we assessed if adult
      laying hens' behaviour and physiological responses, as indicators of their
      personality, were related to their cognitive performance. We assessed their
      behavioural responses to a tonic immobility test, an open field test, and a
      manual restraint test, and measured plasma corticosterone levels after manual
      restraint. After that, hens (n=20) were trained in a pre-set training schedule to
      associate a colour-cue with a reward. In a two-choice go-go test, hens needed to
      choose between a baited or non-baited food container displayed randomly on the
      left or right side of an arena. Success in learning was related to personality,
      with better performance of hens which showed a reactive personality type by a
      long latency to walk, struggle or vocalize during the tests. Only eight out of 20
      hens reached the training criteria. The non-learners showed a strong side
      preference during all training days. Side preferences were strong in hens with
      high levels of plasma corticosterone and with a long duration of tonic
      immobility, indicating that fearful, stress-sensitive hens are more prone to
      develop side biases. Our results show that learning can be hindered by side
      biases, and fearful animals with a more proactive personality type are more
      sensitive to develop such biases.

PMID- 27876640
TI  - Physiological state tunes mesolimbic signaling: Lessons from sodium appetite and
      inspiration from Randall R. Sakai.
AB  - Sodium deficit poses a life-threatening challenge to body fluid homeostasis and
      generates a sodium appetite - the behavioral drive to ingest sodium. Dr. Randall
      R. Sakai greatly contributed to our understanding of the hormonal responses to
      negative sodium balance and to the central processing of these signals.
      Reactivity to the taste of sodium solutions and the motivation to seek and
      consume sodium changes dramatically with body fluid balance. Here, we review
      studies that collectively suggest that sodium deficit recruits the mesolimbic
      system to play a role in the behavioral expression of sodium appetite. The
      recruitment of the mesolimbic system likely contributes to intense sodium seeking
      and reinforces sodium consumption observed in deficient animals. Some of the
      hormones that are released in response to sodium deficit act directly on both
      dopamine and nucleus accumbens elements. Moreover, the taste of sodium in sodium
      deficient rats evokes a pattern of dopamine and nucleus accumbens activity that
      is similar to responses to rewarding stimuli. A very different pattern of
      activity is observed in non-deficient rats. Given the well-characterized
      endocrine response to sodium deficit and its central action, sodium appetite
      becomes an ideal model for understanding the role of mesolimbic signaling in
      reward, reinforcement and the generation of motivated behavior.

PMID- 27876642
TI  - Arabidopsis NF-YCs Mediate the Light-Controlled Hypocotyl Elongation via
      Modulating Histone Acetylation.
AB  - Light is a crucial environmental signal that promotes photomorphogenesis, the
      developmental process with a series of light-dependent alterations for plants to
      adapt various external challenges. Chromatin modification has been proposed to be
      involved in such light-mediated growth, but the underlying mechanism is still
      elusive. In this study, we identified four Arabidopsis thaliana Nuclear Factor-YC
      homologs, NF-YC1, NF-YC3, NF-YC4, and NF-YC9 (NF-YCs), which function redundantly
      as repressors of light-controlled hypocotyl elongation via histone deacetylation.
      Obvious etiolation phenotypes are observed in NF-YCs loss-of-function mutant
      seedlings grown under light conditions, including significant elongated
      hypocotyls and fewer opened cotyledons. We found that NF-YCs interact with
      histone deacetylase HDA15 in the light, co-target the promoters of a set of
      hypocotyl elongation-related genes, and modulate the levels of histone H4
      acetylation on the associated chromatins, thus repressing gene expression. In
      contrast, NF-YC-HDA15 complex is dismissed from the target genes in the dark,
      resulting in increased level of H4 acetylation and consequent etiolated growth.
      Further analyses revealed that transcriptional repression activity of NF-YCs on
      the light-controlled hypocotyl elongation partially depends on the deacetylation
      activity of HDA15, and loss of HDA15 function could rescue the short-hypocotyl
      phenotype of NF-YCs overexpression plants. Taken together, our results indicate
      that NF-YC1, NF-YC3, NF-YC4, and NF-YC9 function as transcriptional co-repressors
      by interacting with HDA15 to inhibit hypocotyl elongation in photomorphogenesis
      during the early seedling stage. Our findings highlight that NF-YCs can modulate
      plant development in response to environmental cues via epigenetic regulation.

PMID- 27876644
TI  - Dinotefuran-induced morphophysiological changes in semi-engorged females
      Rhipicephalus sanguineus Latreille, 1806 (Acari: Ixodidae) ticks: Ultra
      structural evaluation.
AB  - The present study demonstrated the effects of dinotefuran (active ingredient of
      the acaricide Protetor Pet(r)) on the ovary and midgut cells of semi engorged R.
      sanguineus females exposed to different concentrations of this chemical. For
      this, 120 semi-engorged females were divided into four treatment groups with 30
      individuals each: group I or control (distilled water), group II (5000ppm),
      groups III (6250ppm) and group IV (8334ppm of dinotefuran). All the ticks were
      immersed in the different concentrations of dinotefuran or in distilled water for
      5min and then dried and kept in BOD incubator for 7days. The results showed
      alterations mainly regarding the damaged cell structures, such as yolk granules,
      organelles and the plasma membrane of the germ cells. In addition, structures
      related with defense mechanisms were found, such as vacuoles, cytoskeletal
      filaments, and myelin figures in the germ cells. Damages in the generative cells
      of the midgut, alterations in the size of digestive cells, the number of
      endosomes, digestive vacuoles, digestive residues, lipid drops and organelles in
      the cytoplasm of the digestive cells and the presence of microvilli in the plasma
      membrane of these cells also demonstrate the progressive damages caused by the
      action of dinotefuran in the midgut and germ cells of R. sanguineus semi-engorged
      females. The concentrations applied partially impaired the digestive processes;
      and, without proper nutrition, all the ectoparasite's physiologic events are
      prevented from occurring, leading the individual to death. The germ cells were
      also damaged, and probably would not be able to advance in their development (I
      V) and complete the vitellogenesis, which would affect the fertility of the
      female and consequently impede the formation of a new individual.

PMID- 27876645
TI  - Diagnostic accuracy of rKLO8 versus rK26 ELISAs for screening of canine visceral
      leishmaniasis.
AB  - Canine visceral leishmaniasis (CVL) represents an important public health issue.
      Despite numerous diagnostic tests available, CVL diagnosis still needs to be
      improved to achieve a more accurate detection rate. Recently, rKLO8, a new
      antigenic protein of Sudanese Leishmania donovani, was studied for the first time
      in diagnosis of human visceral leishmaniasis (HVL) and showed good performance.
      The present study aimed to evaluate serum reactivity to rKL08 and the reference
      antigen rK26, and to compare both diagnostic proteins with the combined DPP(r)
      CVL rapid test and ELISA (EIE-Bio-Manguinhos) confirmatory test, which are both
      recommended for the diagnosis of CVL in Brazil. Serum samples of dogs were
      grouped into: (I) DPP(r)/EIE negative (n=100) and (II) DPP(r)/EIE positive sera
      (n=100). Enhanced levels of IgG, mainly IgG2, to both rKLO8 and rK26 were found
      in group II. Sensitivity was 68% and 77% and specificity was 92% and 91%, for
      rKLO8 and rK26 antigens, respectively. Moreover, the combination of rKLO8 and
      rK26 antigens (rKLO8+rK26) exhibited higher sensitivity (85%) and specificity
      (93%). Thus, our results show that apart from the improved diagnostic power of
      rKLO8 in HVL, this new antigen is also suitable for the diagnosis of CVL.
      Further, the combination of rKLO8 and rK26 antigens increases the diagnostic
      accuracy of CVL.

PMID- 27876643
TI  - The emergence of arthropod-borne viral diseases: A global prospective on dengue,
      chikungunya and zika fevers.
AB  - Arthropod-borne viruses (arboviruses) present a substantial threat to human and
      animal health worldwide. Arboviruses can cause a variety of clinical
      presentations that range from mild to life threatening symptoms. Many arboviruses
      are present in nature through two distinct cycles, the urban and sylvatic cycle
      that are maintained in complex biological cycles. In this review we briefly
      discuss the factors driving the emergence of arboviruses, such as the
      anthropogenic aspects of unrestrained human population growth, economic expansion
      and globalization. Also the important aspects of viruses and vectors in the
      occurrence of arboviruses epidemics. The focus of this review will be on dengue,
      zika and chikungunya viruses, particularly because these viruses are currently
      causing a negative impact on public health and economic damage around the world.

PMID- 27876647
TI  - The invasive Asian tiger mosquito Aedes albopictus (Diptera: Culicidae) in
      Germany: Local reproduction and overwintering.
AB  - Within the framework of a German mosquito monitoring programme, the
      'Mueckenatlas' (mosquito atlas) has been established as an instrument of citizen
      participation in mosquito mapping. In 2015, a strikingly large number of Aedes
      albopictus, which had not been considered established in Germany, was submitted.
      Three of six collection sites showed local reproduction, with demonstration of
      developmental stages over three months at two sites. The third populated site was
      checked only once in October. Developmental stages of Ae. albopictus were found
      again at these three sites in spring 2016, including one site in southeastern
      Germany where reproduction had already been documented in 2014. Although
      population genetic analyses performed on specimens collected at the latter
      locality in 2014 and 2015 did not provide proof for hibernation, the finding of
      developmental stages at this and two other very same sites as in the year before
      and at very early times in the season strongly suggest accomplished overwintering
      of Ae. albopictus in Germany. Obviously, the second extremely mild winter in
      Germany in a row and ongoing adaptation of Ae. albopictus to the temperate
      European climate allow the species to push northwards from endemic regions in the
      south. Due to the vector competence of Ae. albopictus for numerous pathogens,
      including dengue, chikungunya and Zika viruses, action should be taken
      immediately after the detection of local reproduction to eliminate the
      populations.

PMID- 27876646
TI  - Outcome of oral infection in mice inoculated with Trypanosoma cruzi IV of the
      Western Brazilian Amazon.
AB  - A new epidemiological view of American trypanosomiasis or Chagas disease has been
      formulated in recent decades. Oral transmission of the etiological agent of
      Chagas disease, Trypanosoma cruzi, has been the most common form of transmission.
      The T. cruzi discrete typing units TcI and TcIV have been involved in tens
      outbreaks of acute cases of Chagas disease in the Brazilian Amazon region. We
      investigated the intensity of infection in mice that were orally inoculated (OR
      group) with four strains of TcIV that were isolated from two outbreaks of acute
      Chagas disease that was orally acquired in the state of Amazonas, Brazil. We
      compared the OR group with mice that were intraperitoneally inoculated (IP
      group). Blood samples were analyzed by fresh blood examination, hemoculture, and
      conventional and qualitative real-time polymerase chain reaction (PCR). Samples
      of different tissues were analyzed by quantitative real-time PCR. The OR group
      exhibited a higher maximum peak of parasitemia, greater rates of positivity, and
      higher parasite loads in different tissues during acute infection compared with
      the IP group, indicating a greater intensity of orally acquired infection. Mice
      that were orally inoculated with TcIV strains that were obtained from two
      outbreaks of orally acquired Chagas disease in Amazonas, Brazil, exhibited a more
      intense course of infection compared with intraperitoneally inoculated mice,
      reflected by higher levels of parasitemia and parasite loads.

PMID- 27876648
TI  - Mosquitoes of the Caatinga: 1. Adults stage survey and the emerge of seven news
      species endemic of a dry tropical forest in Brazil.
AB  - The Caatinga is the least known Brazilian biome in terms of the diversity of
      Culicidae. No systematic study of the diversity or ecology of the mosquitoes of
      this biome is available, despite the importance of vector diseases in Brazil. The
      present study addressed the mosquito biodiversity in the Caatinga biome by
      sampling adult populations. Specimens were sampled monthly from March 2013 to
      September 2014 in a Caatinga conservation unit located in the Brazilian semiarid
      zone. Mosquito collections were carried out in Shannon traps from late afternoon
      to early evening, and manual aspiration was used to capture diurnal species as
      well. A total of 4,692 mosquitoes were collected. The most dominant and constant
      species were all undescribed species belonging to the genera Wyeomyia and
      Runchomyia, which together represented 80% of the specimens. The most abundant
      species of epidemiological importance was Haemagogus (Con.) leucocelaenus. The
      abundance of mosquitoes was positively associated with the relative humidity and
      temperature recorded during the month preceding the collection date. In the
      Caatinga, the diversity of adult mosquitoes was associated with the availability
      (quantity and diversity) of natural larval habitats found in the different
      phytophysiognomies of the biome, which vary according to temperature and
      humidity. The number of species unknown to science reflects the levels of
      endemism that exist in the study area, and reinforces the need to further
      taxonomic investigation in the biome.

PMID- 27876649
TI  - Memories of environmental change and local adaptations among molapo farming
      communities in the Okavango Delta, Botswana-A gender perspective.
AB  - This paper focuses on ways in which three riparian communities (Xobe, Shorobe and
      Tubu) practising flood recession (molapo) farming along the fringes of the
      Okavango Delta in Ngamiland District in north-western Botswana, present memories
      of experiential impacts of and adaptation to key environmental and anthropogenic
      change events. Participatory methodological tools were used to capture local
      knowledge of people who had resided in the Okavango wetlands for many years.
      Findings indicate that key environmental change events were characterized by
      intergenerational experiences of severe and frequent droughts, floods, and
      recurrent outbreaks of human and animal disease. These events had impacted
      livelihoods and well-being of communities. Community adaptation strategies were
      embedded in local institutions of governance, especially chieftainship and the
      Kgotla, as legitimate platforms for community re-organization against
      unpredictable environmental change. We concluded that policy/program formulation
      processes need to take cognisance of local communities' historical knowledge of
      environmental change and adaptation. In particular it emerged that men and women,
      and people of different ages have differentiated memories of historical events
      which are complementary and necessary in developing a comprehensive adaptation
      strategy.

PMID- 27876650
TI  - Viruses of parasites as actors in the parasite-host relationship: A "menage a
      trois".
AB  - The complex parasite-host relationship involves multiple mechanisms. Moreover,
      parasites infected by viruses modify this relationship adding more complexity to
      the system that now comprises three partners. Viruses infecting parasites were
      described several decades ago. However, until recently little was known about the
      viruses involved and their impact on the resulting disease caused to the hosts.
      To clarify this situation, we have concentrated on parasitic diseases caused to
      humans and on how virus-infected parasites could alter the symptoms inflicted on
      the human host. It is clear that the effect caused to the human host depends on
      the virus and on the parasite it has infected. Consequently, the review is
      divided as follows: Viruses with a possible effect on the virulence of the
      parasite. This section reviews pertinent articles showing that infection of
      parasites by viruses might increase the detrimental effect of the tandem virus
      parasite on the human host (hypervirulence) or decrease virulence of the parasite
      (hypovirulence). Parasites as vectors affecting the transmission of viruses. In
      some cases, the virus-infected parasite might facilitate the transfer of the
      virus to the human host. Parasites harboring viruses with unidentified effects on
      their host. In spite of recently renewed interest in parasites in connection with
      their viruses, there still remains a number of cases in which the effect of the
      virus of a given parasite on the human host remains ambiguous. The triangular
      relationship between the virus, the parasite and the host, and the modulation of
      the pathogenicity and virulence of the parasites by viruses should be taken into
      account in the rationale of fighting against parasites.

PMID- 27876651
TI  - Ventral Striatum Functional Connectivity during Rewards and Losses and
      Symptomatology in Depressed Patients.
AB  - BACKGROUND: The ventral striatum (VS) and striatal network supports goal
      motivated behavior. Identifying how depressed patients differ in their striatal
      network during the processing of emotionally salient events is a step towards
      uncovering biomarkers for diagnosis and treatment. METHODS: 38 depressed and 30
      healthy adults completed a task that examined brain activation to the
      anticipation and receipt of monetary rewards and losses. Data were collected
      using a 3T Siemens Trio scanner. Functional connectivity differences were
      examined with seeds in the Left or Right VS. FC estimates were regressed on
      specific symptoms. RESULTS: Depressed patients displayed higher functional
      connectivity between the VS and midline cortical areas during loss versus reward
      trials. Anhedonia and depressed mood were associated to fairly similar striatal
      circuits but suicidality was associated to a unique VS-midline structures
      coupling, while depression severity was linked to higher VS to caudate and
      precuneus connectivity during loss versus reward trials. CONCLUSIONS: Depression
      is characterized by excessive VS coupling to cognitive control and associative
      networks during losses versus rewards. High VS to midline cortical structures
      coupling may index suicidality.

PMID- 27876653
TI  - Manual segmentation of the human bed nucleus of the stria terminalis using 3T
      MRI.
AB  - The bed nucleus of the stria terminalis (BNST)-a small gray matter region located
      in the basal forebrain-has been implicated in both anxiety and addiction based on
      compelling evidence from rodent and non-human primate studies. However, the
      BNST's small size and proximity to other gray matter regions has hindered non
      invasive study in human subjects using standard neuroimaging methods. While
      initial studies have benefitted from a BNST mask created from a single human
      subject using a 7T scanner, individual variability is likely-especially in
      patient populations-thus a manual segmentation protocol is needed. Here we report
      on the development of a reliable manual segmentation protocol performed on 3T MRI
      images using a scanning sequence that provides high gray matter/white
      matter/cerebrospinal fluid contrast. Inter- and intra-rater reliabilities,
      measured in 10 healthy individuals, demonstrate that the protocol can be reliably
      implemented (intra-rater Dice similarity coefficient>=0.85, inter-rater>=0.77).
      This BNST tracing protocol provides the necessary foundation for future 3T MRI
      studies of the BNST in healthy controls and patient populations.

PMID- 27876652
TI  - Isoflurane exposure leads to apoptosis of neurons and oligodendrocytes in 20- and
      40-day old rhesus macaques.
AB  - Previously we reported that a 5-hour exposure of 6-day-old (P6) rhesus macaques
      to isoflurane triggers robust neuron and oligodendrocyte apoptosis. In an attempt
      to further describe the window of vulnerability to anesthetic neurotoxicity, we
      exposed P20 and P40 rhesus macaques to 5h of isoflurane anesthesia or no exposure
      (control animals). Brains were collected 3h later and examined
      immunohistochemically to analyze neuronal and glial apoptosis. Brains exposed to
      isoflurane displayed neuron and oligodendrocyte apoptosis distributed throughout
      cortex and white matter, respectively. When combining the two age groups
      (P20+P40), the animals exposed to isoflurane had 3.6 times as many apoptotic
      cells as the control animals. In the isoflurane group, approximately 66% of the
      apoptotic cells were oligodendrocytes and 34% were neurons. In comparison, in our
      previous studies on P6 rhesus macaques, approximately 52% of the dying cells were
      glia and 48% were neurons. In conclusion, the present data suggest that the
      window of vulnerability for neurons is beginning to close in the P20 and P40
      rhesus macaques, but continuing for oligodendrocytes.

PMID- 27876654
TI  - Fast Bayesian whole-brain fMRI analysis with spatial 3D priors.
AB  - Spatial whole-brain Bayesian modeling of task-related functional magnetic
      resonance imaging (fMRI) is a great computational challenge. Most of the
      currently proposed methods therefore do inference in subregions of the brain
      separately or do approximate inference without comparison to the true posterior
      distribution. A popular such method, which is now the standard method for
      Bayesian single subject analysis in the SPM software, is introduced in Penny et
      al. (2005b). The method processes the data slice-by-slice and uses an approximate
      variational Bayes (VB) estimation algorithm that enforces posterior independence
      between activity coefficients in different voxels. We introduce a fast and
      practical Markov chain Monte Carlo (MCMC) scheme for exact inference in the same
      model, both slice-wise and for the whole brain using a 3D prior on activity
      coefficients. The algorithm exploits sparsity and uses modern techniques for
      efficient sampling from high-dimensional Gaussian distributions, leading to speed
      ups without which MCMC would not be a practical option. Using MCMC, we are for
      the first time able to evaluate the approximate VB posterior against the exact
      MCMC posterior, and show that VB can lead to spurious activation. In addition, we
      develop an improved VB method that drops the assumption of independent voxels a
      posteriori. This algorithm is shown to be much faster than both MCMC and the
      original VB for large datasets, with negligible error compared to the MCMC
      posterior.

PMID- 27876655
TI  - Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious
      sensory input in specific brain regions: Insights into a possible mechanism for
      analgesia.
AB  - Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field
      stimulation - GFS) is an emerging therapeutic approach to alleviate chronic pain.
      Here we describe blood oxygen-level dependent (BOLD) functional magnetic
      resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat
      model that replicates clinical GFS using an electrode implanted adjacent to the
      DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD
      fMRI response in brain regions previously associated with sensory and pain
      related response, such as primary/secondary somatosensory cortex, retrosplenial
      granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus,
      and amygdala. These regions differentially demonstrated either positive or
      negative correlation to the acute noxious stimulation paradigm, in agreement with
      previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the
      global BOLD response to noxious stimulation in these regions. This BOLD signal
      attenuation persisted for 20minutes after the GFS was discontinued. Control
      experiments in sham-operated animals showed that the attenuation was not due to
      the effect of repetitive noxious stimulation. Additional control experiments also
      revealed minimal BOLD fMRI response to GFS at therapeutic intensity when
      presented in a standard block-design paradigm. High intensity GFS produced a BOLD
      signal map similar to acute noxious stimulation when presented in a block-design.
      These findings are the first to identify the specific brain region responses to
      neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced
      treatment of chronic pain.

PMID- 27876656
TI  - Postural Sway, Balance Confidence, and Fear of Falling in Women With Knee
      Osteoarthritis in Comparison to Matched Controls.
AB  - BACKGROUND: Osteoarthritis (OA) is a chronic degenerative disease that commonly
      affects the knee joints. Individuals older than 65 years of age with knee OA have
      a greater risk of falls. However, there has been limited examination of the
      parameters of postural sway (increased time, speed, and postural sway area
      [center of pressure{CoP}]), and OA of the knee. OBJECTIVES: The primary objective
      of this study was to determine whether the CoP variables discriminate between
      patients with knee OA and matched healthy volunteers, and to correlate the CoP
      variables with the Activities-Specific Balance Confidence Scale (ABC) and Falls
      Self-Efficacy Scale (FES). The secondary objective was to compare the CoP of
      older women with OA with a control group in bipedal support condition with eyes
      opened and closed. DESIGN: Cross-sectional study. SETTING: University
      Biomechanics Laboratory. PARTICIPANTS: A total of 22 participants were divided
      into the following 2 groups of 11 participants each: an OA group (mean = 68
      years, standard deviation = 7.4 years) and a control group (mean = 66 years,
      standard deviation = 4.4 years). METHODS: Static postural balance was measured by
      a portable force platform. Data were collected in both visual conditions (eyes
      open and closed), in random order. Three attempts of 30 seconds were allowed for
      each participant on the force platform, with a 1-minute interval between
      attempts. MAIN OUTCOME MEASURE: Variables were the CoP total displacement of sway
      (TDS, in centimeters), anteroposterior amplitude displacement (APAD, in
      centimeters), medial-lateral amplitude displacement (MLAD, in centimeters), total
      mean velocity (TMV, in centimeters per second), and dispersion of the center of
      pressure (AREA, in centimeters squared). RESULTS: The postural sway analysis
      found statistically significant differences in the eyes open condition for the
      TDS (P = .020), APAD (P = .042), TMV (P = .010), and AREA (P = .045). In the
      discriminant analysis, none of the CoP variables were able to classify the groups
      (P = .15). The correlation analysis showed that only the AREA with eyes closed
      was associated with the ABC Scale (rho = -0.42). CONCLUSIONS: Women with knee OA
      had greater postural sway when compared with a control group for the eyes open
      condition. CoP variables could not discriminate between the groups. The AREA was
      negatively correlated with the ABC Scale, when the eyes were closed. LEVEL OF
      EVIDENCE: III.

PMID- 27876657
TI  - Clinical Predictors of Intracranial Injuries in Infants with Minor Head Trauma.
AB  - OBJECTIVE: Minor head trauma is common in children. Although most cases are
      nonsignificant, minor head trauma can lead to preventable intracranial injuries.
      The aim of this study was to identify clinical predictors of intracranial
      injuries in infants with minor head trauma. METHODS: Between 2006 and 2013, we
      retrospectively enrolled infants <11 months old with minor head trauma. Data
      recorded included age, sex, cause of trauma, fall height, vomiting, bad temper,
      size and location of scalp hematoma, fracture, and intracranial injuries on
      computed tomography. RESULTS: Of 549 enrolled infants, 15 (3%) sustained
      traumatic intracranial injuries: epidural hematoma in 7, subarachnoid hemorrhage
      in 4, subdural hematoma in 3, and cerebral contusion in 1. Intracranial injuries
      were found in 8 of 98 infants who had fallen from a >60 cm height, 1 in 197 with
      fall height >30 cm, and none in 44 with fall height <=30 cm (P = 0.0001); 1 of 2
      with scalp hematomas >6 cm, 10 of 35 with hematomas >3 cm, and 2 of 121 with
      hematomas <=3 cm (P = 0.0001); and 9 of 28 with temporal hematoma, 2 of 15 with
      parietal hematoma, 2 of 22 with occipital hematoma, and none of 98 with frontal
      hematoma (P = 0.0001). Logistic regression analysis showed that scalp hematoma
      was related to intracranial injuries (hazard ratio = 21.127, P = 0.0001), whereas
      age, sex, fall, vomiting, and bad temper were not. CONCLUSIONS: Fall height and
      size and location of scalp hematoma were associated with intracranial injuries.
      These factors should be considered when making decisions on radiologic
      examinations of infants with minor head trauma.

PMID- 27876658
TI  - Stent Placement for Carotid Web.
AB  - BACKGROUND: The carotid web is an intraluminal shelf-like projection arising from
      the posterior wall of the carotid bifurcation and an uncommon etiology of
      ischemic strokes. We describe the feasibility of endovascular stent placement to
      treat this condition. CASE REPORT: A 47-year-old woman presented with a sudden
      occlusion of the right middle cerebral artery. Computed tomography angiography
      and digital subtraction angiography showed a carotid web in the ipsilateral
      carotid bifurcation. Treatment included mechanical thrombectomy for the middle
      cerebral artery occlusion and carotid stent placement to prevent further ischemic
      episodes from the carotid web. At the 6-month follow-up, good apposition of the
      stent against the artery wall was noted, and the patient was free of neurologic
      symptoms. CONCLUSIONS: Carotid artery stent placement is a feasible option in the
      management of carotid webs.

PMID- 27876659
TI  - Surgical Treatment for Patients with Moyamoya Syndrome and Type 1
      Neurofibromatosis.
AB  - INTRODUCTION: The current study describes the impact of surgery in preventing
      follow-up ipsilateral transient ischemic attacks (TIAs)/strokes in an East Coast
      North American cohort of patients with both moyamoya syndrome (MMS) and
      neurofibromatosis type 1 (NF1) (MMS-NF1). METHODS: We retrospectively reviewed
      records of patients with MMS and NF1 at the Johns Hopkins Medical Institutions
      from 1990-2014. Baseline characteristics and follow-up results including
      subsequent ipsilateral strokes were collected and compared between a
      revascularization group (group 1) and a conservatively managed group (group 2) on
      a per-hemisphere basis. RESULTS: A total of 9 patients (14 hemispheres) were
      included in our study. The average age of all patients at NF1 diagnosis was 2.1
      +/- 7.7 years, with 6 being female (66.7%). The average age of all patients at
      MMS diagnosis was 10.4 +/- 16.6 years with the median age being 7.7 years (range:
      4.1-27.0 years). Race distribution was: White (n = 4, 44.4%), Black (n = 3,
      33.3%), and Asian (n = 2, 22.2%). Four patients (44.5%) experienced
      cerebrovascular manifestations of MMS before MMS diagnosis. Group 1 was younger
      at MMS diagnosis (P = 0.009), likely with a more acute symptom onset (P = 0.077).
      Management strategies were: pial synangiosis (n = 3, 21.4%) and conservative (n =
      11, 78.6%). During an average follow-up period of 6.28 +/- 2.0 years, no
      ipsilateral TIAs/strokes were observed for group 1; conversely, 2 ipsilateral
      TIAs (18.2%) and 2 ipsilateral strokes (18.2%) occurred in group 2. CONCLUSIONS:
      In our study of non-Asian patients with MMS-NF1, revascularization reduced stroke
      recurrence and deterioration of symptoms. However, more studies are warranted to
      further explore the role of revascularization procedures given the rarity of this
      disease combination.

PMID- 27876660
TI  - Total Resection of Brainstem Extension of Tentorial Schwannoma Using an Occipital
      Transtentorial Approach.
AB  - BACKGROUND: Approximately 60 cases of schwannoma unrelated to the cranial nerve
      have been reported, and only 12 arose from the tentorium. We present a case of
      tentorial schwannoma extending into the pons and midbrain without cranial nerve
      involvement, which was almost totally resected with an occipital transtentorial
      approach. CASE DESCRIPTION: A 37-year-old man was admitted to our institution
      with memory disturbance beginning 2 years ago and gait disturbance from 1 year
      ago. Magnetic resonance imaging on admission revealed a heterogeneously enhanced
      33 * 33 * 35 mm tumor in the pons and midbrain, and a dural tail sign connecting
      the lesion to the tentorial edge. Gross total resection of the tumor was
      performed with an occipital transtentorial approach. The trochlear nerve was
      identified and preserved, and the tumor did not involve this cranial nerve. The
      tumor was firmly attached to the edge of tentorium, and extended into the pons
      with sharp tumor border. Postoperative recovery was good, and brain magnetic
      resonance imaging performed 2 months after the surgical procedure revealed gross
      total removal of the lesion without signs of recurrence, but a slightly enhanced
      lesion in the right edge of the tentorium. CONCLUSIONS: The occipital
      transtentorial approach provides a direct approach to tentorial schwannoma,
      resulting in total resection even if the tumor extends into the pons and
      midbrain.

PMID- 27876661
TI  - Fusion 3-Dimensional Angiography of Both Internal Carotid Arteries in the
      Evaluation of Anterior Communicating Artery Aneurysms.
AB  - BACKGROUND: To determine whether fusion 3-dimensional (3D) angiography of both
      internal carotid arteries can better disclose vascular details in patients
      diagnosed with anterior communicating artery (ACoA) aneurysms by computed
      tomography angiography (CTA) or magnetic resonance angiography (MRA). METHODS:
      Thirty-eight patients diagnosed with ACoA aneurysms by CTA or MRA were evaluated
      by the new postprocessing feature, fusion 3D angiography, with results
      individually interpreted by 4 experts. Those experts compared fusion 3D
      angiography with dominant A1 side single 3D angiography to define advantages and
      disadvantages for ACoA aneurysms. Patients with unilateral A1 aplasia or
      rudimentary A1 were excluded. Patients who showed any disadvantages with this
      additional feature were classified as group 1, those with no advantages were
      classified as group 2, those with 1 or 2 advantages were classified as group 3,
      and those with 3 or more advantages were classified as group 4. Radiologic and
      clinical results were also evaluated. RESULTS: Of the 38 patients, 33 (87%)
      benefited from fusion 3D angiography, including 17 in group 3 and 16 in group 4;
      of the remaining patients, 1 was classified as group 1 and 4 were classified as
      group 2. Representative 5 categories of advantage to fusion angiography were
      found and summarized by the 4 experts. All 33 patients showed defining the exact
      anatomy of the ACoA, and 22 (67%) showed full angiographic features of A2 or A3,
      including branches. CONCLUSIONS: Fusion 3D angiography can significantly
      contribute to a better understanding of the complex anatomy of the anterior
      cerebral artery-ACoA complex, which is essential for successful treatment
      planning for ACoA aneurysms.

PMID- 27876662
TI  - Views on Careers in Clinical Neurosciences Among Neurosurgeons and Neurologists
      in China.
AB  - BACKGROUND: China has a large and aging population. The need for physicians with
      training in clinical neurosciences will grow. There is little known regarding the
      factors that lead physicians in China to pursue careers in clinical
      neurosciences. The objective of this study was to garner a clearer understanding
      of factors that influence physicians to pursue careers in neurosurgery and
      neurology in China. METHODS: We surveyed attendees at a national neuroscience
      conference on the factors that influence their pursuit of careers in clinical
      neurosciences. Responses were quantified on a Likert scale. One-way analysis of
      variance was used to compare different groups of respondents. RESULTS: Factors
      associated with the intellectual elements of the specialties were rated most
      highly. Differences were noted between respondents, with trainees rating
      lifestyle-related factors more highly compared with attending physicians.
      CONCLUSIONS: The intellectual challenges are important factors for physicians in
      China influencing the pursuit of careers in the clinical neurosciences. This
      finding echoes results found elsewhere in the world. However, differences with
      trainees elsewhere in the world emerge when evaluating additional factors
      influencing trainees pursuing careers in the clinical neurosciences. Trainees in
      China rate educational experiences and mentorship more highly, whereas U.S.
      trainees rate altruistic goals more highly. This study provides a clearer
      understanding of factors influencing career choice among clinical neuroscientists
      in China.

PMID- 27876663
TI  - A Review of Stem Cell Therapy for Spinal Cord Injury: Large Animal Models and the
      Frontier in Humans.
AB  - OBJECTIVE: To review the literature of spinal cord injury and stem cell therapy
      for large animal models and incorporate those results into an understanding of
      stem cell therapy for human cord injury. METHODS: Review of the literature.
      RESULTS: Eleven canine studies were identified and 3 sub-human primate studies
      were identified showing variable results. CONCLUSIONS: Stem cell therapy is a
      promising therapeutic option for patients with spinal cord injury; however, the
      technology has many un-answered questions and further research is needed.

PMID- 27876664
TI  - Isolated Hypertrophic Neuropathy of the Oculomotor Nerve.
AB  - BACKGROUND: Hypertrophic neuropathy is a rare entity commonly associated with
      peripheral nerve, characterized by onion bulb formations. Its cranial nerve
      involvement is very rare; only 7 cases have been found in the literature. CASE
      DESCRIPTION: A 32-year-old white man with a 5-year history of intermittent right
      retro-orbital headache and mild right ptosis presented to the Neurosurgery
      Clinic. A magnetic resonance imaging of his brain demonstrated an enhancing
      lesion associated with the right third nerve. He underwent biopsy of the lesion,
      and its pathology report confirmed the diagnosis of hypertrophic neuropathy.
      Within 4 months, his third nerve palsy had completely resolved and was
      functioning fully. CONCLUSIONS: Here, we report a first case of isolated
      hypertrophic neuropathy involving the oculomotor nerve.

PMID- 27876665
TI  - Recruitment in Clinical Trials: The Use of Zelen's Prerandomization in Recent
      Neurovascular Studies.
AB  - OBJECTIVE: Randomized allocation of treatment options is not well accepted within
      the clinical community. Some methods of implementation may be received more
      favorably than others. Prerandomization may be an acceptable means to facilitate
      recruitment in some clinical trials. METHODS: We first compare randomization and
      prerandomization using illustrative neurovascular trials. We review some problems
      with conventional trials, Zelen's prerandomization as an alternative method, and
      the ethical issues that have surrounded prerandomization since its inception in a
      historic trial. Conventional and Zelen's randomization are then compared with
      other means to provide and verify care in the context of clinical uncertainty.
      RESULTS: The major problem with conventional randomization is that consent is
      requested for 2 management options, one of which the patient will not receive.
      The problem with prerandomization is that treatment is allocated before the
      patient has consented to trial participation. Prerandomization may trade
      recruitment difficulties for excessive crossovers. However, other ways to
      practice under uncertainty and verify patient outcomes, such as case series and
      registries, are more ethically and scientifically problematic. CONCLUSIONS: Until
      the ethical functions of randomized allocation of selected treatment options in
      the care of patients are recognized by the neurovascular community, Zelen's
      prerandomization may help recruitment into difficult trials and contribute a
      means to provide best possible care in the presence of uncertainty.

PMID- 27876667
TI  - Comparative efficacy and acceptability of electroconvulsive therapy versus
      repetitive transcranial magnetic stimulation for major depression: A systematic
      review and multiple-treatments meta-analysis.
AB  - BACKGROUNDS: The effects of electroconvulsive therapy (ECT) and bilateral, left
      prefrontal, and right prefrontal repetitive transcranial magnetic stimulation
      (rTMS) on major depressive disorder (MDD) have not been adequately addressed by
      previous studies. Here, a multiple-treatments meta-analysis, which incorporates
      evidence from direct and indirect comparisons from a network of trials, was
      performed to assess the efficacy and acceptability of these four treatment
      modalities on MDD. METHOD: The literature was searched for randomized controlled
      trials (RCTs) on ECT, bilateral rTMS, and unilateral rTMS for treating MDD up to
      May 2016. The main outcome measures were response and drop-out rates. RESULTS:
      Data were obtained from 25 studies consisting of 1288 individuals with MDD. ECT
      was non-significantly more efficacious than B-rTMS, R-rTMS, and L-rTMS. Left
      prefrontal rTMS was non -significantly less efficacious than all other treatment
      modalities. In terms of acceptability, R-rTMS was non-significantly better
      tolerated than ECT, B-rTMS, and L-rTMS. ECT was the most efficacious treatment
      with the cumulative probabilities of being the most efficacious treatment being:
      ECT (65%), B-rTMS (25%), R-rTMS (8%), and L-rTMS (2%). R-rTMS was the best
      tolerated treatment with the cumulative probabilities of being the best-tolerated
      treatment being: R-rTMS (52%), B-rTMS (17%), L-rTMS (16%), and ECT (14%).
      Coherence analysis detected no statistically significant incoherence in any
      comparisons of direct with indirect evidence for the response rate and drop-out
      rate. CONCLUSIONS: ECT was the most efficacious, but least tolerated, treatment,
      while R-rTMS was the best tolerated treatment for MDD. B-rTMS appears to have the
      most favorable balance between efficacy and acceptability.

PMID- 27876666
TI  - Comparison of the Stereotactic Accuracies of Function-Guided Deep Brain
      Stimulation, Calculated Using Multitrack Target Locations Geometrically Inferred
      from Three-Dimensional Trajectory Rotations, and of Magnetic Resonance Imaging
      Guided Deep Brain Stimulation and Outcomes.
AB  - OBJECTIVE: In previous studies, multitrack trajectories in deep brain stimulation
      (DBS) have usually been approximated. Using a geometrically more accurate method,
      we compared the stereotactic accuracy of DBS with multitrack microelectrode
      recording and awake stimulation (function group) and MRI-guided DBS (MRI group).
      METHODS: One hundred and seventy-two leads used in DBS between April 2014 and
      January 2016 were evaluated for stereotactic errors. Targets were the subthalamic
      nucleus (STN, 139 leads) or globus pallidus interna (GPi, 33 leads). We
      geometrically calculated shifted-track targets by considering the three
      dimensional stereotactic ring and arc rotations. Stereotactic errors were
      calculated using Euclidean distances perpendicular to trajectories. Motor
      outcomes according to the Unified Parkinson's Disease Rating Scale (UPDRS) part
      III, improvement percentages by stimulations, were analyzed in 24 patients with 1
      year follow-ups. RESULTS: Functional evaluation tended to increase stereotactic
      errors in the STN function group (n = 129; 1.4 +/- 0.7 mm) more than in the STN
      MRI group (n = 10; 1.0 +/- 0.6 mm; P = 0.06). Leads with higher stereotactic
      errors (n = 65; 1.6 +/- 0.7 mm; P < 0.001) than the center-track leads (n = 64;
      1.2 +/- 0.7 mm) were selectively track shifted. Track-shifted leads approached
      MRI targets in 86% (56/65 leads). Lower stereotactic errors tended to correlate
      with a better outcome (P = 0.095). Distances to MRI targets >2.5 mm tended to
      relate to a worse outcome (P = 0.087). Stereotactic errors were lower (n = 33;
      0.9 +/- 0.5 mm) in the GPi MRI group. CONCLUSIONS: Multitrack DBS using
      intraoperative functional evaluation resulted in worse stereotactic accuracy than
      did MRI-guided DBS. However, track shifts in function-guided DBS can approach MRI
      targets effectively.

PMID- 27876668
TI  - Activation of the orbitofrontal and anterior cingulate cortices during the
      expression of a naturalistic compulsive-like behavior in the rabbit.
AB  - We propose that maternal nest building in the female laboratory rabbit is a
      useful model for compulsions in obsessive-compulsive disorder (OCD). This
      repetitive behavior comprises collecting straw, depositing it into the nest box,
      and then returning to collect more straw. We reasoned that if "straw carrying"
      behavior is homologous to compulsive behavior, then it should be associated with
      activation of prefrontal regions associated with OCD, namely, the orbitofrontal
      and anterior cingulate cortices (OFC and ACC, respectively). In the present
      study, we quantified c-FOS immunoreactivity in the ACC, OFC, premotor (PM),
      infralimbic (IL), prelimbic (PL), and piriform (PI) cortices of: (1) pregnant
      female rabbits that were given straw (PREG+STRAW); (2) pregnant rabbits that were
      not given straw (PREG); (3) estrous rabbits that were given straw
      (ESTROUS+STRAW); (4) estrous rabbits that were not given straw (ESTROUS). After
      1h, all females were sacrificed and processed for brain c-FOS immunoreactivity.
      We found that pregnant rabbits showed lower latencies to interact with the straw
      than estrous rabbits, and that pregnant rabbits displayed straw carrying, while
      estrous rabbits did not. c-FOS expression was increased in the OFC, ACC, and PI
      in the PREG+STRAW compared to all other groups. By contrast, c-FOS expression in
      all other regions was greater in PREG+STRAW compared to PREG, but not different
      from ESTROUS+STRAW. These results point to an important role for the OFC, ACC,
      and PI in initiating repetitive straw-carrying behavior, and further support the
      proposal that this behavior can serve as a model for compulsions in OCD.

PMID- 27876669
TI  - Ginsenoside Rg1-induced antidepressant effects involve the protection of
      astrocyte gap junctions within the prefrontal cortex.
AB  - Ginsenoside Rg1 (Rg1) exhibits antidepressant-like activity by increasing
      neurogenesis and dendritic spine density without discernible side effects.
      However, the molecular mechanisms underlying Rg1 antidepressant activity remain
      poorly understood. As the dysfunction of gap junctions between astrocytes in the
      prefrontal cortex (PFC) is implicated in major depression disorder, the aim of
      this study was to investigate the effects of Rg1 on astrocyte gap junctions in
      the PFC. Rats exposed to chronic unpredictable stress (CUS) were administered Rg1
      (5, 10, and 20mg/kg) for 28days and analyzed for depressive symptoms using the
      sucrose preference and forced swimming tests. Functional and morphological
      changes of gap junction channels in the PFC were evaluated using dye transfer and
      electron microscopy, respectively. The expression of connexin 43 (Cx43) was
      analyzed by western blotting. Rg1 markedly alleviated depression-like behavior in
      rats. Long-term Rg1 treatment of CUS-exposed rats also significantly prevented
      the decrease in dye diffusion and improved the ultrastructure of astrocyte gap
      junctions in the PFC, indicating beneficial effects on the functional activity of
      gap junction channels in the brain. In addition, Rg1 upregulated Cx43 expression
      in the PFC reduced by CUS exposure, which significantly correlated with its
      antidepressant-like effects. The results demonstrate that Rg1-induced
      antidepressant effects are might be mediated, in part, by protecting astrocyte
      gap junctions within the prefrontal cortex.

PMID- 27876670
TI  - A model of dynamic stability of H3K9me3 heterochromatin to explain the resistance
      to reprogramming of differentiated cells.
AB  - Despite their dynamic nature, certain chromatin marks must be maintained over the
      long term. This is particulary true for histone 3 lysine 9 (H3K9) trimethylation,
      that is involved in the maintenance of healthy differentiated cellular states by
      preventing inappropriate gene expression, and has been recently identified as the
      most efficient barrier to cellular reprogramming in nuclear transfer experiments.
      We propose that the capacity of the enzymes SUV39H1/2 to rebind to a minor
      fraction of their products, either directly or via HP1alpha/beta, contributes to
      the solidity of this mark through (i) a positive feedback involved in its
      establishment by the mutual enforcement of H3K9me3 and SUV39H1/2 and then (ii) a
      negative feedback sufficient to strongly stabilize H3K9me3 heterochromatin in
      post-mitotic cells by generating local enzyme concentrations capable of
      counteracting transient bursts of demethylation. This model does not require
      direct molecular interactions with adjacent nucleosomes and is favoured by a
      series of additional mechanisms including (i) the protection of chromatin-bound
      SUV39H1/2 from the turnovers of soluble proteins, which can explain the
      uncoupling between the cellular contents in SUV39H1 mRNA and protein; (ii) the
      cooperative dependence on the local density of the H3K9me3 of HP1alpha/beta
      dependent heterochomatin condensation and, dispensably (iii) restricted enzyme
      exchanges with chromocenters confining the reactive bursts of SUV39H1/2 in
      heterochromatin. This mechanism illustrates how seemingly static epigenetic
      states can be firmly maintained by dynamic and reversible modifications.

PMID- 27876671
TI  - Relevance of the rat lung tumor response to particle overload for human risk
      assessment-Update and interpretation of new data since ILSI 2000.
AB  - The relevance of particle-overload related lung tumors in rats for human risk
      assessment following chronic inhalation exposures to poorly soluble particulates
      (PSP) has been a controversial issue for more than three decades. In 1998, an
      ILSI (International Life Sciences) Working Group of health scientists was
      convened to address this issue of applicability of experimental study findings of
      lung neoplasms in rats for lifetime-exposed production workers to PSPs. A full
      consensus view was not reached by the Workshop participants, although it was
      generally acknowledged that the findings of lung tumors in rats following chronic
      inhalation, particle-overload PSP exposures occurred only in rats and no other
      tested species; and that there was an absence of lung cancers in PSP-exposed
      production workers. Since the publication of the ILSI Workshop report in 2000,
      there have been important new data published on the human relevance issue. A
      thorough and comprehensive review of the health effects literature on poorly
      soluble particles/lung overload was undertaken and published by an ECETOC
      (European Centre for Ecotoxicology and Toxicology of Chemicals) Task Force in
      2013. One of the significant conclusions derived from that technical report was
      that the rat is unique amongst all species in developing lung tumors under
      chronic inhalation overload exposures to PSPs. Accordingly, the objective of this
      review is to provide important insights on the fundamental differences in
      pulmonary responses between experimentally-exposed rats, other experimental
      species and occupationally-exposed humans. Briefly, five central factors are
      described by the following issues. Focusing on these five interrelated/convergent
      factors clearly demonstrate an inappropriateness in concluding that the findings
      of lung tumors in rats exposed chronically to high concentrations of PSPs are
      accurate representations of the risks of lung cancer in PSP-exposed production
      workers. The most plausible conclusion that can be reached is that results from
      chronic particle-overload inhalation studies with PSPs in rats have no relevance
      for determining lung cancer risks in production workers exposed for a working
      lifetime to these poorly soluble particulate-types.

PMID- 27876672
TI  - Is there a human health risk associated with indirect exposure to perfluoroalkyl
      carboxylates (PFCAs)?
AB  - The production and widespread use of poly- and perfluoroalkyl substances (PFAS)
      has led to their presence in the environment, wildlife, and humans. Particularly,
      the perfluoroalkyl carboxylates (PFCAs) are pervasive throughout the world and
      have been found at ng/mL concentrations in human blood. PFCAs, especially those
      having longer carbon chain lengths (>=C6), are associated with developmental and
      hormonal effects, immunotoxicity, and promote tumor growth in rodents through
      their role as PPARalpha agonists. Humans are directly exposed to PFCAs primarily
      through contaminated food, drinking water, and house dust. However, indirect
      exposure to PFCAs through the biotransformation of fluorotelomer-based substances
      may also be a significant, yet relatively underappreciated pathway. We are
      exposed to fluorotelomer-based substances through use of consumer products,
      ingestion of food, or from inhalation of dust particles, but the risk of this
      exposure has been largely uncharacterized. Here, we summarize the work that has
      been done to characterize toxicity of the classes of fluorotelomer-based
      substances shown to biotransform to PFCAs: the polyfluoroalkyl phosphate esters
      (PAPs), fluorotelomer alcohols (FTOHs), fluorotelomer iodides (FTIs), and
      fluorotelomer acrylate monomers (FTAcs). These fluorotelomer-based substances
      biotranform to yield PFCAs, yet also form bioactive intermediate metabolites,
      which have been observed to be more toxic than their corresponding PFCAs. We
      address what is known regarding the toxicity of the fluorotelomer-based
      substances and their metabolites, with focus on covalent binding to biological
      nucleophiles, such as glutathione, proteins, and DNA, as a possible mechanism of
      toxicity that may influence the risk of indirect exposure to PFCAs.

PMID- 27876673
TI  - Extra cellular matrix a modular soil for stem cells.

PMID- 27876674
TI  - Thymic Carcinoma Management Patterns among International Thymic Malignancy
      Interest Group (ITMIG) Physicians with Consensus from the Thymic Carcinoma
      Working Group.
AB  - INTRODUCTION: Thymic carcinomas are rare epithelial malignancies with limited
      data to guide management. METHODS: To identify areas of agreement and variability
      in current clinical practice, a 16-question electronic survey was given to
      members of the International Thymic Malignancy Interest Group (ITMIG). Areas of
      controversy were discussed with the Thymic Carcinoma Working Group and consensus
      was achieved, as described. RESULTS: A total of 100 ITMIG members responded.
      There was general agreement regarding the role for multimodality therapy with
      definitive surgical resection in physically fit patients with advanced but
      resectable disease. Areas of controversy included the need for histologic
      confirmation before surgery, the role of adjuvant therapy, the optimal first-line
      chemotherapy regimen, and the recommended treatment course for marginally
      resectable disease with invasion into the great vessels, pericardium, and lungs.
      CONCLUSIONS: The results of the questionnaire provide a description of the
      management of thymic carcinoma by 100 ITMIG members with a specific interest or
      expertise in thymic malignancies. Although there was agreement in some areas,
      clinical practice appears to vary significantly. There is a great need for
      collaborative research to identify optimal evaluation and treatment strategies.
      Given the need for multimodality therapy in many cases, a multidisciplinary
      discussion of the management of patients with thymic carcinoma is critical.

PMID- 27876675
TI  - A Phase 1/1b Study Evaluating Trametinib Plus Docetaxel or Pemetrexed in Patients
      With Advanced Non-Small Cell Lung Cancer.
AB  - OBJECTIVES: This two-part study evaluated trametinib, a MEK1/2 inhibitor, in
      combination with anticancer agents. Inhibition of MEK, a downstream effector of
      KRAS, demonstrated preclinical synergy with chemotherapy in KRAS-mutant NSCLC
      cell lines. Part 1 of this study identified recommended phase 2 doses of
      trametinib combinations. Part 2, reported herein, evaluated the safety,
      tolerability, pharmacokinetics, and efficacy of trametinib combinations in
      patients with NSCLC with and without KRAS mutations. METHODS: Phase 1b evaluated
      trametinib plus docetaxel with growth factor support (trametinib, 2.0 mg once
      daily, and docetaxel, 75 mg/m2 every 3 weeks) or pemetrexed (trametinib, 1.5 mg
      once daily, and pemetrexed, 500 mg/m2 every 3 weeks). Eligibility criteria for
      the expansion cohorts included metastatic NSCLC with measurable disease, known
      KRAS mutation status, Eastern Cooperative Oncology Group performance status of 1
      or lower, and no more than two prior regimens. RESULTS: The primary end point of
      overall response rate (ORR) was met for both combinations. A confirmed partial
      response (PR) was observed in 10 of the 47 patients with NSCLC who received
      trametinib plus docetaxel (21%). The ORR was 18% (four PRs in 22 patients) in
      those with KRAS wild-type NSCLC versus 24% (six PRs in 25 patients) in those with
      KRAS-mutant NSCLC. Of the 42 patients with NSCLC treated with trametinib plus
      pemetrexed, six (14%) had a PR; the ORR was 17% (four of 23) in patients with
      KRAS-mutated NSCLC versus 11% (two of 19) in KRAS wild-type NSCLC. Adverse events
      most commonly diarrhea, nausea, and fatigue-were manageable. CONCLUSIONS:
      Trametinib-plus-chemotherapy combinations were tolerable. Clinical activity
      exceeding the ORRs previously reported with docetaxel or pemetrexed alone in KRAS
      mutated NSCLC and meeting prespecified criteria was observed.

PMID- 27876677
TI  - Do we really need the full compliance with ERAS protocol in laparoscopic
      colorectal surgery? A prospective cohort study.
AB  - BACKGROUND: Although the relation between adherence to the ERAS protocol and
      clinical outcomes was extensively studied, there is still ongoing discussion on
      the need and feasibility of full compliance in laparoscopic colorectal surgery.
      In this study, we aimed to verify whether a strict adherence to the protocol
      (>90%) leads to further improvement in clinical outcomes compared to high (70
      90%) and low (<70%) compliance groups. MATERIALS AND METHODS: The analysis
      included consecutive prospectively registered patients operated laparoscopically
      for colorectal cancer between January 2012 and December 2015. Patients were
      divided into three groups depending on the compliance with the ERAS protocol:
      <70% (Group 1), 70-90% (Group 2), >90% (Group 3). The measured outcomes were:
      complication rate, readmission rate, recovery parameters (tolerance of early oral
      diet on 1st postoperative day and mobilization of a patient on the day of
      surgery), length of stay (LOS). RESULTS: Group 1 consisted of 70, Group 2 of 65
      and Group 3 of 116 patients. There were no statistical differences between the
      groups based on demographic parameters, stage of cancer and operative parameters
      (operative time, blood loss, conversion rate). The overall compliance with the
      protocol in the study group was 85.6 +/- 11.9%. There was a significant decrease
      in complication rate with increasing compliance (35.7% vs. 36.4% vs. 16.4%, p =
      0.0024) and severity of complications according to the Clavien-Dindo
      classification (p = 0.0198). Moreover, we observed differences in recovery
      parameters between the groups: tolerance of oral diet on the 1st postoperative
      day (52.8% vs. 79.5% vs. 87.9%, p < 0.0001), mobilization of a patient on the day
      of surgery (68.6% vs. 92.3% vs. 99.1%, p < 0.0001), respectively. We also
      observed that with compliance increase, the median LOS decreased (6 vs. 4 vs. 3
      days, p < 0.0001). CONCLUSION: Full implementation of the ERAS protocol
      significantly improves short term outcomes both in comparison to the high- and
      low-compliant groups.

PMID- 27876676
TI  - Anatomical region-dependent enhancement of 3-dimensional chondrogenic
      differentiation of human mesenchymal stem cells by soluble meniscus extracellular
      matrix.
AB  - : Extracellular matrix (ECM) derived from decellularized tissues has been found
      to promote tissue neogenesis, most likely mediated by specific biochemical and
      physical signaling motifs that promote tissue-specific differentiation of
      progenitor cells. Decellularized ECM has been suggested to be efficacious for the
      repair of tissue injuries. However, decellularized meniscus contains a dense
      collagenous structure, which impedes cell seeding and infiltration and is not
      readily applicable for meniscus repair. In addition, the meniscus consists of two
      distinct anatomical regions that differ in vascularity and cellular phenotype.
      The purpose of this study was to explore the region-specific bioactivity of
      solubilized ECM derived from the inner and outer meniscal regions as determined
      in 2D and 3D cultures of adult mesenchymal stem cells (MSCs). When added as a
      medium supplement to 2D cultures of MSCs, urea-extracted fractions of the inner
      (imECM) and outer meniscal ECM (omECM) enhanced cell proliferation while imECM
      most strongly upregulated fibrochondrogenic differentiation on the basis of gene
      expression profiles. When added to 3D cultures of MSCs seeded in photocrosslinked
      methacrylated gelatin (GelMA) hydrogels, both ECM fractions upregulated
      chondrogenic differentiation as determined by gene expression and protein
      analyses, as well as elevated sulfated glycosaminoglycan sGAG content, compared
      to ECM-free controls. The chondrogenic effect at day 21 was most pronounced with
      imECM supplementation, but equivalent between ECM groups by day 42. Despite
      increased cartilage matrix, imECM and omECM constructs possessed compressive
      moduli similar to controls. In conclusion, soluble meniscal ECM may be considered
      for use as a tissue-specific reagent to enhance chondrogenesis for MSC-based 3D
      cartilage tissue engineering. STATEMENT OF SIGNIFICANCE: The inner region of the
      knee meniscus is frequently injured and possesses a poor intrinsic healing
      capacity. Solubilized extracellular matrix (ECM) derived from decellularized
      meniscus tissue may promote homologous differentiation of progenitor cells,
      thereby enhancing fibrocartilage formation within a meniscal lesion. However, the
      meniscus possesses regional variation in ultrastructure, biochemical composition,
      and cell phenotype, which may affect the bioactivity of soluble ECM derived from
      different regions of decellularized menisci. In this study, we demonstrate that
      urea-extracted fractions of ECM derived from the inner and outer regions of
      menisci enhance chondrogenesis in mesenchymal stem cells seeded in 3-dimensional
      photocrosslinkable hydrogels and that this effect is more strongly mediated by
      inner meniscal ECM. These findings suggest region-specific bioactivity of
      decellularized meniscal ECM.

PMID- 27876678
TI  - Definition and identification of small RNA sponges: Focus on miRNA sequestration.
AB  - Targeting RNAs appears as an important opportunity to modulate biological
      processes. Here, we overviewed critical parameters implied in RNAs competition to
      bind small RNAs. These competitions influence small RNA availability and thereby
      gene expression and cell fate. We focused on the ability of RNAs to sequester
      small RNA, mainly the microRNAs (miRNAs) and proposed experimental workflows to
      demonstrate the existence and activity of RNA-sponge. From this basic science, we
      detailed tailored oligonucleotides, developed to challenge the binding of small
      RNA. In vitro and in vivo, these tailored oligonucleotides efficiently restore
      small RNA activity by preventing their sequestration on RNA-sponges.

PMID- 27876680
TI  - Identification of unknown RNA partners using MAPS.
AB  - Recent advances in high-throughput sequencing have led to an explosion in the
      rate of small regulatory RNAs (sRNAs) discovery among bacteria. However, only a
      handful of them are functionally characterized. Most of the time, little to no
      targets are known. In Lalaouna et al. (2015), we proposed a new technology to
      uncover sRNAs targetome, which is based on the MS2-affinity purification (MAPS).
      We were able to prove its efficiency by applying it on well-characterized sRNAs
      of Escherichia coli. Thereafter, we adapted the procedure to other kind of RNA
      (mRNAs and tRNA-derived RNA fragments) and bacteria (pathogenic or Gram-positive
      strains). Here, we clearly report all improvements and adjustments made to MAPS
      technology since it was originally reported.

PMID- 27876679
TI  - Predicting the pathogenicity of aminoacyl-tRNA synthetase mutations.
AB  - Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed, essential enzymes
      responsible for charging tRNA with cognate amino acids-the first step in protein
      synthesis. ARSs are required for protein translation in the cytoplasm and
      mitochondria of all cells. Surprisingly, mutations in 28 of the 37 nuclear
      encoded human ARS genes have been linked to a variety of recessive and dominant
      tissue-specific disorders. Current data indicate that impaired enzyme function is
      a robust predictor of the pathogenicity of ARS mutations. However, experimental
      model systems that distinguish between pathogenic and non-pathogenic ARS variants
      are required for implicating newly identified ARS mutations in disease. Here, we
      outline strategies to assist in predicting the pathogenicity of ARS variants and
      urge cautious evaluation of genetic and functional data prior to linking an ARS
      mutation to a human disease phenotype.

PMID- 27876682
TI  - Mycophenolate mofetil is a valid option in patients with inflammatory bowel
      disease resistant to TNF-alpha inhibitors and conventional immunosuppressants.
AB  - BACKGROUND: Few studies investigated the role of mycophenolate mofetil in
      inflammatory bowel disease, and none of them had specifically focused on patients
      with previous multiple intolerances and/or nonresponses to conventional
      immunosuppressants and biologics. AIMS: To evaluate clinical benefit and
      tolerability profile of mycophenolate mofetil in patients with inflammatory bowel
      disease and limited treatment options. METHODS: All consecutive patients with
      previous multiple intolerances and/or nonresponses to immunosuppressants and
      biologics who started an off-label treatment with mycophenolate mofetil from
      January 2014 to February 2016 were entered in a prospectively maintained
      database. RESULTS: Twenty-four patients were included. Four weeks after
      initiation of mycophenolate mofetil therapy, a steroid-free remission was
      achieved in 4 patients (16.7%), while a clinical response in 13 (54.1%). At the
      end of follow-up, 12 patients (50.0%) remained on mycophenolate mofetil. Six
      achieved and maintained steroid-free remission throughout the study period
      (25.0%), and a further 6 patients (25.0%) achieved a clinical response with
      complete discontinuation of steroids. Twelve patients (50.0%) were considered as
      treatment failure, and five of them underwent surgery. CONCLUSIONS: This is the
      first experience reporting a clinical benefit and tolerability of mycophenolate
      mofetil in patients with inflammatory bowel disease and multiple previous
      failures to other immunosuppressants and/or biologics.

PMID- 27876683
TI  - Preferences of referring physicians regarding the role of radiologists as direct
      communicators of test results.
AB  - PURPOSE: Currently, there is a growing need for patient-centered radiology in
      which radiologists communicate with patients directly. The aim of this study is
      to investigate the preferences of referring physicians (RPs) regarding direct
      communication between radiologists and patients. METHODS: This study was
      conducted in a single academic hospital using a survey form. The survey items
      investigated the preferences of RPs regarding: 1. who should be the communicator
      of test results when a patient with abnormal findings requests information (the
      options were the radiologist; another health professional with communication
      skills training (CST); and the RP with CST); and 2. how the communication
      activity should be conducted if the radiologist is obliged (or chooses) to
      communicate with the patient directly (the options were that the disclosure
      should be limited to the findings in the radiology report; the radiologist should
      emphasize that the RP is the primary physician; and the communication activity
      should be conducted in accordance with guidelines established by consensus). The
      respondents were 101 RPs from various fields of specialty; they were asked to
      rate the items using a 5-point Likert scale. The effects of age, sex, field of
      specialty (surgical vs. nonsurgical), and total years of experience as a medical
      specialist on the ratings were statistically compared. RESULTS: Most RPs
      preferred that the radiologist transmit the information to the RP without
      communicating directly with the patient (89.1%). Although 69.3% of the RPs
      declared that health professionals with CST have priority in communication, 86.1%
      declared that the RP should be the person who received CST. If the radiologist
      communicates with patients directly, the RPs favored that 1. the disclosure
      should be limited to the findings in the radiology report (95%); 2. the
      communication activity should include an emphasis on the RP as the patient's
      primary agent (84.1%); and 3. communication should be conducted in accordance
      with guidelines established by consensus (73.2%). The percentage of strong
      opinions did not change significantly with regard to age, sex, field of
      specialty, or total years of experience, except that surgeons expressed strong
      disagreement with delegating the communication activity to another health
      professional who received CST (chi2 = 9.9; P = 0.042). CONCLUSION: These findings
      may serve as a basis to implement institutional and national policies for patient
      centered radiology.

PMID- 27876684
TI  - Do We Still Have a Digital Divide in Mental Health? A Five-Year Survey Follow-up.
AB  - BACKGROUND: Nearly everyone in society uses the Internet in one form or another.
      The Internet is heralded as an efficient way of providing mental health
      treatments and services. However, some people are still excluded from using
      Internet-enabled technology through lack of resources, skills, and confidence.
      OBJECTIVE: Five years ago, we showed that people with severe mental illness were
      at risk of digital exclusion, especially middle-aged patients with psychosis
      and/or people from black or minority ethnic groups with psychosis. An
      understanding of the breadth of potential digital exclusion is vital for the
      implementation of digital health services. The aim of this study is to understand
      the context of digital exclusion for people who experience mental illness.
      METHODS: We conducted a survey involving people with a primary diagnosis of
      psychosis or depression in London, United Kingdom. A total of 241 participants
      were recruited: 121 with psychosis and 120 with depression. The majority of
      surveys were collected face-to-face (psychosis: n=109; depression: n=71).
      Participants answered questions regarding familiarity, access, use, motivation,
      and confidence with Internet-enabled technologies (ie, computers and mobile
      phones). Variables predicting digital exclusion were identified in regression
      analyses. The results were compared with the survey conducted in 2011. RESULTS:
      Digital exclusion has declined since 2011. Online survey collection introduced
      biases into the sample, masking those who were likely to be excluded. Only 18.3%
      (20/109) of people with psychosis in our sample were digitally excluded, compared
      with 30% (28/93) in 2011 (chi21=3.8, P=.04). People with psychosis had less
      confidence in using the Internet than people with depression (chi21=7.4, P=.004).
      Only 9.9% (24/241) of participants in the total sample were digitally excluded,
      but the majority of these people had psychosis (n=20). Those with psychosis who
      were digitally excluded were significantly older than their included peers
      (t30=3.3, P=.002) and had used services for longer (t97=2.5, P=.02). Younger
      people were more likely to use mobile phones. Digitally excluded participants
      cited a lack of knowledge as a barrier to digital inclusion, and most wanted to
      use the Internet via computers (rather than mobile phones). CONCLUSIONS: Digital
      exclusion is lower, but some remain excluded. Facilitating inclusion among this
      population means helping them develop skills and confidence in using technology,
      and providing them with access. Providing mobile phones without basic information
      technology training may be counterproductive because excluded people may be
      excluded from mobile technology too. An evidence-based digital inclusion strategy
      is needed within the National Health Service to help digitally excluded
      populations access Internet-enabled services.

PMID- 27876681
TI  - Site-selective orientated immobilization of antibodies and conjugates for
      immunodiagnostics development.
AB  - Immobilized antibody systems are the key to develop efficient diagnostics and
      separations tools. In the last decade, developments in the field of biomolecular
      engineering and crosslinker chemistry have greatly influenced the development of
      this field. With all these new approaches at our disposal, several new
      immobilization methods have been created to address the main challenges
      associated with immobilized antibodies. Few of these challenges that we have
      discussed in this review are mainly associated to the site-specific
      immobilization, appropriate orientation, and activity retention. We have
      discussed the effect of antibody immobilization approaches on the parameters on
      the performance of an immunoassay.

PMID- 27876685
TI  - Efficacy of Mobile Serious Games in Increasing HIV Risk Perception in Swaziland:
      A Randomized Control Trial (SGprev Trial) Research Protocol.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) and acquired immune deficiency
      syndrome (AIDS) continue to be a major public health problem in Sub-Saharan
      Africa (SSA), particularly in Swaziland, which has the highest HIV prevalence in
      this region. A wide range of strategies and interventions have been used to
      promote behavior change, though almost all such interventions have involved mass
      media. Therefore, innovative behavior change strategies beyond mass media
      communication are urgently needed. Serious games have demonstrated effectiveness
      in advancing health in the developed world; however, no rigorous serious games
      interventions have been implemented in HIV prevention in SSA. OBJECTIVE: We plan
      to test whether a serious game intervention delivered on mobile phones to
      increase HIV risk perception, increase intention to reduce sexual partnerships,
      and increase intention to know own and partners HIV status will be more effective
      compared with current prevention efforts. METHODS: This is a two-arm randomized
      intervention trial. We will recruit 380 participants who meet the following
      eligibility criteria: 18-29 years of age, own a smartphone running an Android
      based operating system, have the WhatsApp messaging app, live in Swaziland, and
      can adequately grant informed consent. Participants will be allocated into a
      smartphone interactive, educational story game, and a wait-list control group in
      a 1:1 allocation ratio. Subsequently, a self-administered Web-based questionnaire
      will be issued at baseline and after 4 weeks of exposure to the game. We
      hypothesize that the change in HIV risk perception between pre- and post
      intervention assessment is greater in the intervention group compared with the
      change in the control group. Our primary hypothesis is based on the assumption
      that increased perceived risk of HIV provides cues to engage in protective
      behavior. Our primary outcome measure is HIV risk perceived mean change between
      pre- and post-intervention compared with the mean change in the wait-list control
      group at 4-weeks post-intervention. We will use standardized regression
      coefficients to calculate the effect of the intervention on our primary outcome
      with P values. We will conduct both intention to treat and as treated analysis.
      RESULTS: This study is funded by Hayao Nakayama Foundation for Science &
      Technology and Culture; Grant number H26-A2-41. The research and development
      approval has been obtained from Kyoto University Graduate School and Faculty of
      Medicine Ethics Committee, Japan, and Swaziland's Ministry of Health Ethics and
      Scientific committee. Results are expected in February 2017. CONCLUSIONS: This
      study will provide evidence on the efficiency of a mobile phone interactive game
      in increasing HIV risk perception in Swaziland. Our findings may also be
      generalizable to similar settings in SSA. TRIAL REGISTRATION: University Hospital
      Medical Information Network Clinical Trial Registry ID number (UMIN
      CTR):UMIN000021781; URL:https://upload.umin.ac.jp/cgi-open
      bin/ctr_e/ctr_view.cgi?recptno=R000025103 (Archived by WebCite at
      http://www.webcitation.org/6hOphB11a).

PMID- 27876686
TI  - Encouraging Patient Portal Use in the Patient-Centered Medical Home: Three
      Stakeholder Perspectives.
AB  - BACKGROUND: Health care organizations are increasingly offering patients access
      to their electronic medical record and the ability to communicate with their
      providers through Web-based patient portals, thus playing a prominent role within
      the patient-centered medical home (PCMH). However, despite enthusiasm, adoption
      remains low. OBJECTIVE: We examined factors in the PCMH context that may affect
      efforts to improve enrollment in a patient portal. METHODS: Using a
      sociotechnical approach, we conducted qualitative, semistructured interviews with
      patients and providers from 3 primary care clinics and with national leaders from
      across a large integrated health care system. RESULTS: We gathered perspectives
      and analyzed data from 4 patient focus groups and one-on-one interviews with 1
      provider from each of 3 primary care clinics and 10 program leaders. We found
      that leaders were focused on marketing in primary care, whereas patients and
      providers were often already aware of the portal. In contrast, both patients and
      providers cited administrative and logistical barriers impeding enrollment.
      Further, although leadership saw the PCMH as the logical place to focus
      enrollment efforts, providers and patients were more circumspect and expressed
      concern about how the patient portal would affect their practice and experience
      of care. Further, some providers expressed ambivalence about patients using the
      portal. Despite absence of consensus on how and where to encourage portal
      adoption, there was wide agreement that promoting enrollment was a worthwhile
      goal. CONCLUSIONS: Patients, clinicians, and national leaders agreed that efforts
      were needed to increase enrollment in the patient portal. Opinions diverged
      regarding the suitability of the PCMH and, specifically, the primary care clinic
      for promoting patient portal enrollment. Policymakers should consider diverse
      stakeholder perspectives in advance of interventions to increase technology
      adoption.

PMID- 27876687
TI  - Methods for Evaluating Respondent Attrition in Web-Based Surveys.
AB  - BACKGROUND: Electronic surveys are convenient, cost effective, and increasingly
      popular tools for collecting information. While the online platform allows
      researchers to recruit and enroll more participants, there is an increased risk
      of participant dropout in Web-based research. Often, these dropout trends are
      simply reported, adjusted for, or ignored altogether. OBJECTIVE: To propose a
      conceptual framework that analyzes respondent attrition and demonstrates the
      utility of these methods with existing survey data. METHODS: First, we suggest
      visualization of attrition trends using bar charts and survival curves. Next, we
      propose a generalized linear mixed model (GLMM) to detect or confirm significant
      attrition points. Finally, we suggest applications of existing statistical
      methods to investigate the effect of internal survey characteristics and patient
      characteristics on dropout. In order to apply this framework, we conducted a case
      study; a seventeen-item Informed Decision-Making (IDM) module addressing how and
      why patients make decisions about cancer screening. RESULTS: Using the framework,
      we were able to find significant attrition points at Questions 4, 6, 7, and 9,
      and were also able to identify participant responses and characteristics
      associated with dropout at these points and overall. CONCLUSIONS: When these
      methods were applied to survey data, significant attrition trends were revealed,
      both visually and empirically, that can inspire researchers to investigate the
      factors associated with survey dropout, address whether survey completion is
      associated with health outcomes, and compare attrition patterns between groups.
      The framework can be used to extract information beyond simple responses, can be
      useful during survey development, and can help determine the external validity of
      survey results.

PMID- 27876688
TI  - Online Concerns of Parents Suspecting Autism Spectrum Disorder in Their Child:
      Content Analysis of Signs and Automated Prediction of Risk.
AB  - BACKGROUND: Online communities are used as platforms by parents to verify
      developmental and health concerns related to their child. The increasing public
      awareness of autism spectrum disorders (ASD) leads more parents to suspect ASD in
      their child. Early identification of ASD is important for early intervention.
      OBJECTIVE: To characterize the symptoms mentioned in online queries posed by
      parents who suspect that their child might have ASD and determine whether they
      are age-specific. To test the efficacy of machine learning tools in classifying
      the child's risk of ASD based on the parent's narrative. METHODS: To this end, we
      analyzed online queries posed by parents who were concerned that their child
      might have ASD and categorized the warning signs they mentioned according to ASD
      specific and non-ASD-specific domains. We then used the data to test the efficacy
      with which a trained machine learning tool classified the degree of ASD risk.
      Yahoo Answers, a social site for posting queries and finding answers, was mined
      for queries of parents asking the community whether their child has ASD. A total
      of 195 queries were sampled for this study (mean child age=38.0 months; 84.7%
      [160/189] boys). Content text analysis of the queries aimed to categorize the
      types of symptoms described and obtain clinical judgment of the child's ASD-risk
      level. RESULTS: Concerns related to repetitive and restricted behaviors and
      interests (RRBI) were the most prevalent (75.4%, 147/195), followed by concerns
      related to language (61.5%, 120/195) and emotional markers (50.3%, 98/195). Of
      the 195 queries, 18.5% (36/195) were rated by clinical experts as low-risk, 30.8%
      (60/195) as medium-risk, and 50.8% (99/195) as high-risk. Risk groups differed
      significantly (P<.001) in the rate of concerns in the language, social,
      communication, and RRBI domains. When testing whether an automatic classifier
      (decision tree) could predict if a query was medium- or high-risk based on the
      text of the query and the coded symptoms, performance reached an area under the
      receiver operating curve (ROC) curve of 0.67 (CI 95% 0.50-0.78), whereas
      predicting from the text and the coded signs resulted in an area under the curve
      of 0.82 (0.80-0.86). CONCLUSIONS: Findings call for health care providers to
      closely listen to parental ASD-related concerns, as recommended by screening
      guidelines. They also demonstrate the need for Internet-based screening systems
      that utilize parents' narratives using a decision tree questioning method.

PMID- 27876691
TI  - Performance Assessment of a Plate Beam Splitter for Deep-Ultraviolet Raman
      Measurements with a Spatial Heterodyne Raman Spectrometer.
AB  - In earlier works, we demonstrated a high-resolution spatial heterodyne Raman
      spectrometer (SHRS) for deep-ultraviolet (UV) Raman measurements, and showed its
      ability to measure UV light-sensitive compounds using a large laser spot size. We
      recently modified the SHRS by replacing the cube beam splitter (BS) with a custom
      plate beam splitter with higher light transmission, an optimized
      reflectance/transmission ratio, higher surface flatness, and better refractive
      index homogeneity than the cube beam splitter. Ultraviolet Raman measurements
      were performed using a SHRS modified to use the plate beam splitter and a
      matching compensator plate and compared to the previously described cube beam
      splitter setup. Raman spectra obtained using the modified SHRS exhibit much
      higher signals and signal-to-noise (S/N) ratio and show fewer spectral artifacts.
      In this paper, we discuss the plate beam splitter SHRS design features, the
      advantages over previous designs, and discuss some general SHRS issues such as
      spectral bandwidth, S/N ratio characteristics, and optical efficiency.

PMID- 27876689
TI  - Survey Email Scheduling and Monitoring in eRCTs (SESAMe): A Digital Tool to
      Improve Data Collection in Randomized Controlled Clinical Trials.
AB  - BACKGROUND: Electronic questionnaires can ease data collection in randomized
      controlled trials (RCTs) in clinical practice. We found no existing software that
      could automate the sending of emails to participants enrolled into an RCT at
      different study participant inclusion time points. OBJECTIVE: Our aim was to
      develop suitable software to facilitate data collection in an ongoing multicenter
      RCT of low back pain (the Acuback study). For the Acuback study, we determined
      that we would need to send a total of 5130 emails to 270 patients recruited at
      different centers and at 19 different time points. METHODS: The first version of
      the software was tested in a pilot study in November 2013 but was unable to
      deliver multiuser or Web-based access. We resolved these shortcomings in the next
      version, which we tested on the Web in February 2014. Our new version was able to
      schedule and send the required emails in the full-scale Acuback trial that
      started in March 2014. The system architecture evolved through an iterative,
      inductive process between the project study leader and the software programmer.
      The program was tested and updated when errors occurred. To evaluate the
      development of the software, we used a logbook, a research assistant dialogue,
      and Acuback trial participant queries. RESULTS: We have developed a Web-based
      app, Survey Email Scheduling and Monitoring in eRCTs (SESAMe), that monitors
      responses in electronic surveys and sends reminders by emails or text messages
      (short message service, SMS) to participants. The overall response rate for the
      19 surveys in the Acuback study increased from 76.4% (655/857) before we
      introduced reminders to 93.11% (1149/1234) after the new function (P<.001).
      Further development will aim at securing encryption and data storage.
      CONCLUSIONS: The SESAMe software facilitates consecutive patient data collection
      in RCTs and can be used to increase response rates and quality of research, both
      in general practice and in other clinical trial settings.

PMID- 27876692
TI  - Methods for Broadband Spectral Analysis: Intrinsic Fluorescence Temperature
      Sensing as an Example.
AB  - A systematic study was performed on the temperature-dependent fluorescence of
      (Ba,Sr)2SiO4:Eu2+. The barycenter and extended intensity ratio techniques were
      proposed to characterize the broadband fluorescence spectra. These techniques and
      other known methods (listed below) were employed and compared in the fluorescent
      temperature sensing experiment. Multiple sensing functions were obtained using
      the behaviors of: (1) the barycenter location of the emission band; (2) the
      emission bandwidth; and (3) the ratio of intensities at different wavelengths in
      the emission band, respectively. The barycenter technique was not limited by the
      spectrometer resolution and worked well while the peak location method failed.
      All the sensing functions were based on the intrinsic characteristics of the
      fluorescence of the phosphor and demonstrated nearly linear relationships with
      temperature in the measuring range. The multifunctional temperature-sensing
      abilities of the phosphor can be applied in a point thermometer or thermal
      mapping. The new techniques were validated successfully for characterizing
      various spectra.

PMID- 27876690
TI  - "Mommy Blogs" and the Vaccination Exemption Narrative: Results From A Machine
      Learning Approach for Story Aggregation on Parenting Social Media Sites.
AB  - BACKGROUND: Social media offer an unprecedented opportunity to explore how people
      talk about health care at a very large scale. Numerous studies have shown the
      importance of websites with user forums for people seeking information related to
      health. Parents turn to some of these sites, colloquially referred to as "mommy
      blogs," to share concerns about children's health care, including vaccination.
      Although substantial work has considered the role of social media, particularly
      Twitter, in discussions of vaccination and other health care-related issues,
      there has been little work on describing the underlying structure of these
      discussions and the role of persuasive storytelling, particularly on sites with
      no limits on post length. Understanding the role of persuasive storytelling at
      Internet scale provides useful insight into how people discuss vaccinations,
      including exemption-seeking behavior, which has been tied to a recent diminution
      of herd immunity in some communities. OBJECTIVE: To develop an automated and
      scalable machine-learning method for story aggregation on social media sites
      dedicated to discussions of parenting. We wanted to discover the aggregate
      narrative frameworks to which individuals, through their exchange of experiences
      and commentary, contribute over time in a particular topic domain. We also wanted
      to characterize temporal trends in these narrative frameworks on the sites over
      the study period. METHODS: To ensure that our data capture long-term discussions
      and not short-term reactions to recent events, we developed a dataset of 1.99
      million posts contributed by 40,056 users and viewed 20.12 million times indexed
      from 2 parenting sites over a period of 105 months. Using probabilistic methods,
      we determined the topics of discussion on these parenting sites. We developed a
      generative statistical-mechanical narrative model to automatically extract the
      underlying stories and story fragments from millions of posts. We aggregated the
      stories into an overarching narrative framework graph. In our model, stories were
      represented as network graphs with actants as nodes and their various
      relationships as edges. We estimated the latent stories circulating on these
      sites by modeling the posts as a sampling of the hidden narrative framework
      graph. Temporal trends were examined based on monthly user-poststatistics.
      RESULTS: We discovered that discussions of exemption from vaccination
      requirements are highly represented. We found a strong narrative framework
      related to exemption seeking and a culture of distrust of government and medical
      institutions. Various posts reinforced part of the narrative framework graph in
      which parents, medical professionals, and religious institutions emerged as key
      nodes, and exemption seeking emerged as an important edge. In the aggregate
      story, parents used religion or belief to acquire exemptions to protect their
      children from vaccines that are required by schools or government institutions,
      but (allegedly) cause adverse reactions such as autism, pain, compromised
      immunity, and even death. Although parents joined and left the discussion forums
      over time, discussions and stories about exemptions were persistent and robust to
      these membership changes. CONCLUSIONS: Analyzing parent forums about health care
      using an automated analytic approach, such as the one presented here, allows the
      detection of widespread narrative frameworks that structure and inform
      discussions. In most vaccination stories from the sites we analyzed, it is taken
      for granted that vaccines and not vaccine preventable diseases (VPDs) pose a
      threat to children. Because vaccines are seen as a threat, parents focus on
      sharing successful strategies for avoiding them, with exemption being the
      foremost among these strategies. When new parents join such sites, they may be
      exposed to this endemic narrative framework in the threads they read and to which
      they contribute, which may influence their health care decision making.

PMID- 27876693
TI  - A Case of Septic Shock Due to Serratia marcescens Pyelonephritis and Bacteremia
      in a Patient Receiving Empagliflozin.
AB  - Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been associated with
      serious urinary tract infections (UTIs) including pyelonephritis and urosepsis.
      The Food and Drug Administration (FDA) issued a label change to include this
      warning in December 2015 due to a small number of cases (n = 19) reported to the
      FDA Adverse Event Reporting System. Details of these cases are limited and none
      involved empagliflozin. To date, there has been no published literature
      comprehensively describing serious UTIs attributed to empagliflozin. We describe
      a case of septic shock due to Serratia marcescens pyelonephritis and bacteremia
      that required intensive care unit admission in a well-controlled, type 2 diabetic
      patient who had begun taking empagliflozin 2 months prior. The patient was
      treated successfully with intravenous antibiotics followed by oral ciprofloxacin.
      After discontinuation of empagliflozin and completion of antibiotic therapy, no
      subsequent UTIs were documented in the following 4 months.

PMID- 27876695
TI  - Modelling projections for the uptake of edoxaban in an European population to
      2050: effects on stroke, thromboembolism, and health economics perspectives.
AB  - AIMS: In the coming decades, the number of Europeans with atrial fibrillation
      (AF) is set to rise as the population ages, and so with it will the number of
      strokes. The risk of thromboembolism (principally stroke and systemic embolism)
      and death can be reduced by the use of the vitamin K antagonists (VKA, e.g.
      warfarin) and more so by non-VKA oral anticoagulants (NOACs) such as edoxaban.
      METHODS AND RESULTS: We modelled the effect of the increasing use of edoxaban in
      preference to warfarin in a European AF population from both clinical and
      economic perspectives. We estimate that the introduction of NOACs in 2010
      eliminated over 88 000 thromboembolisms and deaths annually, of which over 17 000
      were ischaemic strokes. At a 1-year cost of ?30k per ischaemic stroke, this
      strategy saved ?510 million annually. Should the use of edoxaban increase from
      11% in 2013 to 75% by 2030, we expect that rate of thromboembolism and death will
      fall from 5.67 to 5.42 total events per million patients per year, which will
      further eliminate over 12 000 of these events annually. At an inflation-adjusted
      1-year cost of approximately ?35k per ischaemic stroke, this will save ?44.5
      million each year. At a conservative rate of increase in the AF population of 2.2
      fold from 2005, in 2050 there will be around 180 000 AF-related ischaemic strokes
      that, at an inflation-adjusted cost of around ?62k per stroke, sums to ?11 116
      million. Should the rate of AF rise 2.6-fold from 2005, then in 2050 there will
      be 214 500 ischaemic strokes that will cost around ?13 300 million. CONCLUSION:
      Our data point to a substantial increase in the human and economic cost burden of
      AF and so emphasize the need to reduce this burden. This may be achieved by the
      increased use of oral anticoagulants, particularly with the NOACs such as
      edoxaban.

PMID- 27876694
TI  - Hypersuccinylacetonaemia and normal liver function in maleylacetoacetate
      isomerase deficiency.
AB  - BACKGROUND: A high level of succinylacetone (SA) in blood is a sensitive,
      specific newborn screening marker for hepatorenal tyrosinemia type 1 (HT1, MIM
      276700) caused by deficiency of fumarylacetoacetate hydrolase (FAH). Newborns
      with HT1 are usually clinically asymptomatic but show liver dysfunction with
      coagulation abnormalities (prolonged prothrombin time and/or high international
      normalised ratio). Early treatment with nitisinone (NTBC) plus dietary
      restriction of tyrosine and phenylalanine prevents the complications of severe
      liver disease and neurological crises. METHODS AND RESULTS: Six newborns referred
      for hypersuccinylacetonaemia but who had normal coagulation testing on initial
      evaluation had sequence variants in the GSTZ1 gene, encoding maleylacetoacetate
      isomerase (MAAI), the enzyme preceding FAH in tyrosine degradation. Initial
      plasma SA levels ranged from 233 to 1282 nmol/L, greater than normal (<24 nmol/L)
      but less than the initial values of patients with HT1 (16 944-74 377 nmol/L,
      n=15). Four individuals were homozygous for c.449C>T (p.Ala150Val). One was
      compound heterozygous for c.259C>T (p.Arg87Ter) and an intronic sequence variant.
      In one, a single heterozygous GSTZ1 sequence variant was identified, c.295G>A
      (p.Val99Met). Bacterial expression of p.Ala150Val and p.Val99Met revealed low
      MAAI activity. The six individuals with mild hypersuccinylacetonaemia (MHSA) were
      not treated with diet or nitisinone. Their clinical course has been normal for up
      to 13 years. CONCLUSIONS: MHSA can be caused by sequence variants in GSTZ1. Such
      individuals have thus far remained asymptomatic despite receiving no specific
      treatment.

PMID- 27876697
TI  - Galectin-1 in myelin repair.

PMID- 27876698
TI  - Axl in ovarian cancer: a step forward for clinical breakthrough?

PMID- 27876699
TI  - Redox and metabolic regulation of transcription.

PMID- 27876696
TI  - Stroke prevention strategies in patients with atrial fibrillation and heart valve
      abnormalities: perceptions of 'valvular' atrial fibrillation: results of the
      European Heart Rhythm Association Survey.
AB  - The purpose of this European Heart Rhythm Association (EHRA) Survey was to assess
      the perceptions of 'valvular' atrial fibrillation (AF) and management of AF
      patients with various heart valve abnormalities in daily clinical practice in
      European electrophysiology (EP) centres. Questionnaire survey was sent via the
      Internet to the EHRA-EP Research Network Centres. Of the 52 responding centres,
      42 (80.8%) were university hospitals. Choosing the most comprehensive definition
      of valvular AF, a total of 49 centres (94.2%) encountered a mechanical prosthetic
      heart valve and significant rheumatic mitral stenosis, 35 centres (67.3%) also
      considered bioprosthetic valves, and 25 centres (48.1%) included any significant
      valvular heart disease, requiring surgical repair in the definition of valvular
      AF. Only three centres (5.8%) would define valvular AF as the presence of any
      (even mild) valvular abnormality. None of the centres would use non-vitamin K
      antagonist oral anticoagulants (NOACs) in AF patients with mechanical prosthetic
      valves, only 5 centres (9.8%) would use NOACs in patients with significant mitral
      stenosis, 17 centres (32.7%) would consider the use of NOACs in patients with
      bioprosthetic valves, and 21 centres (41.2%) would use NOACs in patients with a
      non-recent transcatheter valve replacement/implantation, while 13 centres (25.5%)
      would never consider the use of NOACs in AF patients with even mild native heart
      valve abnormality. Our survey showed marked heterogeneity in the definition of
      valvular AF and thromboprophylactic treatments, with the use of variable NOACs in
      patients with valvular heart disease other than prosthetic heart valves or
      significant mitral stenosis, indicating that this term may be misleading and
      should not be used.

PMID- 27876701
TI  - Which TDP-43 aggregates are toxic in ALS?

PMID- 27876700
TI  - Double hit mouse model of Parkinson's disease.

PMID- 27876702
TI  - NRP1 and synapse formation.

PMID- 27876703
TI  - Nicotine inside neurons.

PMID- 27876706
TI  - Reply: The Characteristics about Our Study in Irritable Bowel Syndrome.

PMID- 27876704
TI  - Pancreatic carcinoma-specific immunotherapy using novel tumor specific cytotoxic
      T cells.
AB  - Pancreatic cancer represents one of the most lethal human cancers. Investigation
      of the effective targeting to the tumor cells is essential for both primary
      tumors and metastases. Tumor specific cytotoxic T lymphocytes (CTLs) have
      recently been considered to be the attractive vehicles for delivering therapeutic
      agents toward various tumor diseases. This study was to explore the distribution
      pattern of CTL carrying the lentiviral vectors with the characteristic of
      adenoviral E1 gene under the control of the cell activation-dependent CD40 ligand
      promoter (Lenti/hCD40L/E1AB). Following transduction with adenoviral particles
      containing chimeric type 5 and type 35 fiber proteins (Ad5/35-TRAIL), these CTLs
      produced infectious virus when exposed to SW1990 cells. We found that the novel
      CTL harboring Lenti/hCD40L/E1AB and Ad5/35-TRAIL inhibited pancreatic cancer cell
      growth and angiogenesis in vitro and in vivo. Furthermore, Ad5/35-TRAIL
      transduced CTL induced significant apoptosis in pancreatic carcinoma cell lines
      and upregulated IFN-gamma (IFN-gamma) secretion of CTLs. Importantly, Ad5/35
      TRAIL transduced CTLs had no inhibitory effect on normal cells. Thus, the novel
      CTLs may be safe and feasible for the development of gene therapy approaches to
      pancreatic carcinoma.

PMID- 27876707
TI  - Critical Appraisal of "Association between Diet and Lifestyle Habits and
      Irritable Bowel Syndrome: A Case-Control Study".

PMID- 27876705
TI  - Genome-wide gain-of-function screen for genes that induce epithelial-to
      mesenchymal transition in breast cancer.
AB  - Epithelial to mesenchymal transition (EMT) is a developmental program that has
      been implicated in progression, metastasis and therapeutic resistance of some
      carcinomas. To identify genes whose overexpression drives EMT, we screened a
      lentiviral expression library of 17000 human open reading frames (ORFs) using
      high-content imaging to quantitate cytoplasmic vimentin. Hits capable of
      increasing vimentin in the mammary carcinoma-derived cell line MDA-MB-468 were
      confirmed in the non-tumorigenic breast-epithelial cell line MCF10A. When
      overexpressed in this model, they increased the rate of cell invasion through
      MatrigelTM, induced mesenchymal marker expression and reduced expression of the
      epithelial marker E-cadherin. In gene-expression datasets derived from breast
      cancer patients, the expression of several novel genes correlated with expression
      of known EMT marker genes, indicating their in vivo relevance. As EMT-associated
      properties are thought to contribute in several ways to cancer progression, genes
      identified in this study may represent novel targets for anti-cancer therapy.

PMID- 27876708
TI  - A bio-inspired optical system with a polymer membrane and integrated structure.
AB  - A bio-inspired optical imaging system with a polymer membrane and integrated
      structure is proposed. Similar to the human eye, the presented system has a
      biomimetic multilayered optical structure and utilizes a solid-liquid mixed
      tunable lens as the variable-focus unit. The focal length of the imaging system
      can be adjusted flexibly through the deformation of the tunable lens when it is
      compressed. A detailed description of the design principle, materials and
      fabrication process of the system is presented. The deformation property,
      adjustable range and surface roughness of the tunable lens are measured. Images
      under different displacement loads are captured, and the relationships among the
      back focal length (BFL) and effective focal length (EFL) of the system and the
      change in radius of the tunable lens are analyzed. A 7.6 times variation of the
      BFL is achieved through a tiny alteration in radius of 1.2 mm. All the measured
      resolutions during the deformation stage are larger than 40 line pairs mm-1, and
      the imaging system shows good optical quality and stability. The proposed optical
      system is of interest for the development of compact and stable imaging systems
      with a large zooming range.

PMID- 27876709
TI  - Low-energy microscopic models for iron-based superconductors: a review.
AB  - The development of sensible microscopic models is essential to elucidate the
      normal-state and superconducting properties of the iron-based superconductors.
      Because these materials are mostly metallic, a good starting point is an
      effective low-energy model that captures the electronic states near the Fermi
      level and their interactions. However, in contrast to cuprates, iron-based high-T
      c compounds are multi-orbital systems with Hubbard and Hund interactions,
      resulting in a rather involved 10-orbital lattice model. Here we review different
      minimal models that have been proposed to unveil the universal features of these
      systems. We first review minimal models defined solely in the orbital basis,
      which focus on a particular subspace of orbitals, or solely in the band basis,
      which rely only on the geometry of the Fermi surface. The former, while providing
      important qualitative insight into the role of the orbital degrees of freedom, do
      not distinguish between high-energy and low-energy sectors and, for this reason,
      generally do not go beyond mean-field. The latter allow one to go beyond mean
      field and investigate the interplay between superconducting and magnetic orders
      as well as Ising-nematic order. However, they cannot capture orbital-dependent
      features like spontaneous orbital order. We then review recent proposals for a
      minimal model that operates in the band basis but fully incorporates the orbital
      composition and symmetries of the low-energy excitations. We discuss the results
      of the renormalization group study of such a model, particularly of the interplay
      between superconductivity, magnetism, and spontaneous orbital order, and compare
      theoretical predictions with experiments on iron pnictides and chalcogenides. We
      also discuss the impact of the glide-plane symmetry on the low-energy models,
      highlighting the key role played by the spin-orbit coupling.

PMID- 27876710
TI  - Enhancement of 1,3-Dihydroxyacetone Production from Gluconobacter oxydans by
      Combined Mutagenesis.
AB  - Wild strain L-6 was subjected to combined mutagenesis, including UV irradiation,
      atmospheric and room temperature plasma, and ion beam implantation, to increase
      the yield of 1,3-dihydroxyacetone (DHA). With application of a high-throughput
      screening method, mutant Gluconobacter oxydans I-2-239 with a DHA productivity of
      103.5 g/l in flask-shake fermentation was finally obtained with the starting
      glycerol concentration of 120 g/l, which was 115.7% higher than the wild strain.
      The cultivation time also decreased from 54 h to 36 h. Compared with the wild
      strain, a dramatic increase in enzyme activity was observed for the mutant
      strain, although the increase in biomass was limited. DNA and amino acid sequence
      alignment revealed 11 nucleotide substitutions and 10 amino acid substitutions
      between the sldAB of strains L-6 and I-2-239. Simulation of the 3-D structure and
      prediction of active site residues and PQQ binding site residues suggested that
      these mutations were mainly related to PQQ binding, which was speculated to be
      favorable for the catalyzing capacity of glycerol dehydrogenase. RT-qPCR assay
      indicated that the transcription levels of sldA and sldB in the mutant strain
      were respectively 4.8-fold and 5.4-fold higher than that in the wild strain,
      suggesting another possible reason for the increased DHA productivity of the
      mutant strain.

PMID- 27876711
TI  - Calreticulin Promotes Proliferation and Migration But Inhibits Apoptosis in
      Schwann Cells.
AB  - BACKGROUND Previous studies indicated that calreticulin (CRT) regulated various
      biological processes. This study was aimed to investigate the function of CRT in
      Schwann cells (SCs). MATERIAL AND METHODS SCs were separated from sciatic nerves
      of mice and were transfected with pcDNA3.1-CRT (pc-CRT), small interfering RNA
      targets CRT (siCRT), or their corresponding negative controls. The expression of
      CRT was determined by quantitative reverse transcription PCR (qRT-PCR) and
      Western blot analysis. Then, cell proliferation, migration, and apoptosis were
      measured by 3-(4, 5-dimethylhiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)
      assay, modified 2-chamber migration assay, and flow cytometry, respectively.
      Finally, the phosphorylation levels of key kinases in the phosphatidylinositol-3
      kinase (PI3K)/AKT and the extracellular signal-regulated kinase/ribosomal S6
      kinase 2 (ERK/S6) pathways were detected by Western blot analysis. RESULTS
      Overexpression of CRT remarkably increased viability (P<0.05, P<0.01 or P<0.001)
      and migration (P<0.001), but inhibited apoptosis (P<0.05). The CRT-knockdown
      showed the inverse impacts on viability (P<0.05 or P<0.001), migration (P<0.001),
      and apoptosis (P<0.001). Additionally, the phosphorylation levels of AKT (Thr308
      and Ser473), ERK, and S6 were all up-regulated in CRT-overexpressed cells
      (P<0.001), and were down-regulated in CRT-knockdown cells (P<0.05, P<0.01 or
      P<0.001). CONCLUSIONS Overexpression of CRT in SCs promoted cell proliferation
      and migration but suppressed cell apoptosis. The PI3K/AKT and ERK/S6 pathways
      might be involved in the functional effects of CRT on SCs.

PMID- 27876712
TI  - MiR-30a Decreases Multidrug Resistance (MDR) of Gastric Cancer Cells.
AB  - BACKGROUND The effectiveness of chemotherapy for gastric cancer is largely
      limited by either intrinsic or acquired drug resistance. In this study, we aimed
      to explore the association between miR-30a dysregulation and multidrug resistance
      (MDR) in gastric cancer cells. MATERIAL AND METHODS We recruited 20 patients with
      advanced gastric cancer. Chemosensitivity was assessed after completion of the
      chemotherapy. SGC-7901 and SGC-7901/DDP cells were transfected for miR-30a
      overexpression or knockdown. Then, MTT assay was performed to assess the IC50 of
      DPP and 5-FU in SGC-7901 and SGC-7901/DDP cells. Flow cytometry analysis was used
      to detect DPP- and 5-FU-induced cell apoptosis. Western blot analysis and
      immunofluorescence staining were used to assess EMT of the cells. RESULTS MiR-30a
      was significantly downregulated in the chemoresistant tissues. In both SGC-7901
      and SGC-7901/DDP cells, miR-30a overexpression decreased the expression of P-gp,
      a MDR-related protein. MTT assay and flow cytometry analysis showed that miR-30a
      inhibition increased chemoresistance, while miR-30a overexpression decreased
      chemoresistance in gastric cancer cells. Both Western blot analysis and
      immunofluorescence staining confirmed that miR-30a inhibition decreased E
      cadherin but increased N-cadherin in SGC-7901 cells, while miR-30a overexpression
      increased E-cadherin but decreased N-cadherin in SGC-7901 cells. CONCLUSIONS MiR
      30a can decrease multidrug resistance (MDR) of gastric cancer cells. It is also
      an important miRNA modulating EMT of the cancer cells.

PMID- 27876713
TI  - Role of Acoustic Radiation Force Impulse (ARFI) Elastography in Determination of
      Severity of Benign Prostate Hyperplasia.
AB  - BACKGROUND The aim of this study was to investigate the potential contribution of
      acoustic radiation force impulse (ARFI) elastography to the determination of the
      severity of benign prostate hypertrophy (BPH) by performing shear wave velocity
      (SWV) measurements of the prostate using ARFI technology. MATERIAL AND METHODS
      Sixty BPH patients and 40 healthy volunteers were included in this study. SWV
      measurements of the prostate were performed by transabdominal ultrasonography
      (US), both in the BPH patients and control subjects. The BPH patients also
      underwent uroflowmetry measurements. Using the International Prostate Symptom
      Score (IPSS), the BPH patients were divided into two subgroups, a mild-to
      moderate BPH group and a severe BPH group, to compare SWV values. RESULTS The BPH
      patients had higher SWV values for the central area of the prostate compared to
      the control subjects (2.52+/-0.59 m/s and 1.47+/-0.42 m/s, p<0.01). The SWV
      values of the central area of prostate were higher in the severe BPH group
      compared to the mild-to-moderate BPH group (2.62+/-0.58 and 2.25+/-0.55, p=0.02).
      CONCLUSIONS Our ARFI elastography results indicated that the central prostate SWV
      values of BPH patients were significantly higher relative to those of a healthy
      control group. The central prostate SWV values increased in proportion to the
      increased severity of BPH. Measurement of SWV by ARFI technology constitutes a
      non-invasive alternative to other methods for the determination of BPH severity.

PMID- 27876714
TI  - [Prospects of endoscopic technology for diagnostics of inflammatory periodontal
      disease].
AB  - The aim of the study was to analyze research methods for periodontitis severity
      and elaborate the most effective diagnostic combination. Twenty patients with
      moderate periodontal disease were included in the study. In addition to
      conventional diagnostic methods depth of periodontal pockets (PP) was measured by
      means of endoscopic system and cone bean CT. Differences in PP depth estimated by
      probing and endoscopic evaluation was 1.2+/-0.4 mm proving endoscopic method to
      be useful and most precise tool for periodontal diagnostics.

PMID- 27876715
TI  - [Diagnostics of tooth supporting structures].
AB  - The aim of the study was to assess alveolar bone resorption in patients with
      periodontal disease and individuals with normal periodontal status and coordinate
      resorbtion rates with tooth mobility. Tooth mobility was measured in 19 patients
      with periodontal disease and 17 healthy individuals by two-parametrical
      periodontometry in two different positions: in equilibrium and after pre-loading.
      The level of bone resorption was determined by periodontal probe. Previously
      unknown correlation between tooth mobility and alveolar bone resorption was found
      out meaning that bone atrophy can be determined by tooth mobility.

PMID- 27876716
TI  - [The relationship of molecular genetic markers with clinical signs and risk
      factors of periodontitis].
AB  - The study revealed positive correlation between bleeding on probing and teeth
      loss risk with periodontal hypercolonization by Porphyromonas gingivalis,
      Prevotella intermedia and Treponema denticola. Pathological tooth mobility was
      associated with hypercolonization by P. intermedia and Tannerella forsythensis.
      Expression of IL8, TNF-alpha, MMP8 and MMP9 genes was also assessed in patient
      groups divided according to the depth of periodontal pockets and-the severity of
      chronic periodontitis revealing IL8 as positive diagnostic marker.

PMID- 27876717
TI  - [Lipids peroxidation system in oral fluid of pregnant women with inflammatory
      periodontal disease at different gestation stages].
AB  - Oxidative stress was assessed in 30 pregnant women with inflammatory periodontal
      disease and 20 healthy non-pregnant women. An increase of lipids peroxidation
      intensity and decrease of antioxidative enzymes was revealed. These changes
      progressed during the course of gestation reaching its peak in the III trimester
      and were associated with the clinical signs of periodontal disease.

PMID- 27876718
TI  - [Prevention of the recurrent herpetic stomatitis in employees of Kazan city
      industrial enterprises frequently suffering from acute respiratory viral
      infections].
AB  - Research objective was to study the efficacy of ingavirin for prevention of
      recurrent herpetic stomatitis in employees of Kazan city industrial enterprises
      frequently suffering from acute respiratory viral infections. 128 employees aged
      from 18 to 56 years were included in the study. Clinical and immunological
      efficiency of ingavirin prevention of recurrent herpetic stomatitis is proved by
      estimation of oral cavity local immunity (SlgA, lisozyme), humoral immunity (IgE
      and IgG) and cellular immunity (RBTL with FGA, defined T-lymphocytes). After
      administration of ingavirin significant (p<0.05) increase of lisozyme and SlgA,
      RBTL with FGA, number of T-lymphocytes and IgG concentration was observed. The
      obtained data allow to recommend ingavirin for prevention of recurrent herpetic
      stomatitis.

PMID- 27876719
TI  - [Local anesthesia selection algorithm in patients with concomitant disease. Part
      2.]
AB  - A group of authors presents the rationale for local anesthesia selection in
      patients with concomitant disease based on case history; interaction analysis of
      drugs with local anesthetic and sedation agents; estimation of patient functional
      status; patient anxiety correction; dental care with hemodynamics monitoring. It
      was found that adhering to this algorithm promotes the prevention of urgent
      conditions in outpatient settings.

PMID- 27876720
TI  - [Mechanisms of reparative action of a new repair and protect toothpaste].
AB  - The aim of the study was to assess clinical efficacy of Sensodyne repair and
      protect toothpaste as well as mechanics of its reparative action. Forty-eight
      patients (29 females and 19 males) were included in the study. The participants
      brushed twice daily with Sensodyne toothpaste. In 24 patients in addition to
      clinical examination fluoride, calcium and pH were measured in oral fluid. The
      study showed OHIS reduction by 40.24% and eradication of tooth hypersensitivity
      even after single use of the toothpaste in 90% of patients because of sodium
      monofluorophosphate action.

PMID- 27876721
TI  - [Prevention of lingual nerve damage by removing stones from submandibular
      salivary gland duct].
AB  - The aim of the study was to elaborate lingual nerve sparing procedure of
      submandibular gland duct stones extraction. The study involved 43 patients with
      syalolithiasis treated in Oral Surgery Unit of Central Research Institute of
      Dentistry and Maxillofacial Surgery in 2013-2015. It was shown that to prevent
      lingual nerve and artery injury submandibular salivary gland duct should be
      dissected to the level of obstruction thus allowing adequate visualization of
      anatomical correlations especially when removing stones from the distal part of
      the duct.

PMID- 27876722
TI  - [Comparative analysis of 3D data visibility of the prepared tooth finishing line
      on a synthetic jaw model, captured by international scanners in a laboratory
      conditions].
AB  - The aim of the study was to compare accuracy of digital impression's finishing
      line and the zone under it taken by different intraoral scanning systems.
      Parameters of comparison were: different level of the finishing line to the
      gingiva and width of sulcus after retraction. For this purpose two synthetic jaw
      models with prepared teeth were scanned using intraoral scanning systems: 3D
      Progress (MHT S.P.A., IT - MHT Optic Research AG, CH); True Definition (3M ESPE,
      USA); Trios (3Shape A/S, DNK); CEREC AC Bluecam, CEREC Omnicam (Sirona Dental
      System GmbH, DE); Planscan (Planmeca, FIN) (each n=10). Reference-scanning was
      done by ATOS Core (GOM mbH, DE). The resulting digital impressions were
      superimposed with the master-scan. The lowest measured deviations (trueness) for
      intraoral scanners, where the finishing line was 0.5 mm above gingiva were with
      scanner True Definition - 18.8+/-6.63 (on the finishing line) and 51.0+/-14.33 um
      (0.3 mm under the finishing line). In conditions where finishing line was on the
      same level with gingiva, scanner Trios showed the best results: 17.0+/-3.96 and
      52.7+/-6.52 um. When the finishing line was 0.5 mm under gingiva, none of the
      testing scanners could visualize the zone 0.3 mm lower the finishing line. The
      best results for accuracy o the finishing line in that circumstances showed
      Trios: 15.1+/-5.05 um. The optimum visualization of the finishing line and the
      zone under it was reached when the sulcus was 0.3 mm after retraction. Thus, the
      best accuracy was obtained with Trios: 10.3+/-2.69 (on the finishing line) and
      57.2+/-13.58 um (0.3 mm under finishing line). The results show that intraoral
      scanners also provide enough accuracy for indicating finishing line and the zone
      under it in different conditions of preparation and gingiva retraction. However,
      not all of the testing scanners can properly indicate finishing line and the zone
      under it when shoulder is below gingiva and the width of sulcus is less than 0.2
      mm.

PMID- 27876723
TI  - [Stability of orthodontic correction: preconditions of relapses caused by
      occlusal forces].
AB  - The aim of the study was to determine the prognostic criteria of orthodontic
      treatment success in a group of patients with crowded teeth position and a
      neutral occlusion. The study included 150 patients (123 female and 27 male) with
      the average follow-up of 10.02+/-2.88 years and average retention phase of 6.15+/
      2.98 years. Teeth positions, dental arches form, occlusal contacts and
      periodontal status were studied. Dentition changes after orthodontic correction
      should be considered as a result of adaptive compensatory balance. The resultant
      force acting on teeth and the direction of it determine displacement of teeth.
      The leading relapse precontidion induced by the occlusal forces was the
      interference of the canines, mandible deviation and asymmetry, muscle tone
      disorders.

PMID- 27876724
TI  - [Stevens-Johnson syndrome in the dentist practice].
AB  - The article presents a clinical example of the manifestations of Stevens-Johnson
      syndrome in a young patient. The patient had extensive lesions of the mucosa of
      the mouth, inflammation of the conjunctiva, itchy skin rashes. Good clinical
      result was obtained due to the prescribe treatment. The treatment included
      desensitizing, detoxifying and anti-inflammatory systematic and topical therapy.

PMID- 27876725
TI  - [On the occasion of the 80th anniversary of the Department of
      Otorhinolaryngology, Dagestan State Medical Academy of the Russian Ministry of
      Health and the 130th birthday anniversary of professor V.A. Chudnosovetov, the
      founder and the first head of the Department and the affiliated clinic].

PMID- 27876726
TI  - [The diagnostics and treatment of otogenic intracranial complications].
AB  - We have undertaken the analysis of medical records of the patients presenting
      with major otogenic intracranial complications (OICC) including purulent
      meningitis, brain or cerebellum abscess, and thrombosis of sigmoid sinus. The
      presence of isolated and combined variants of otogenic intracranial complications
      was documented in 112 (43%) and 148 (56.9%) patients, respectively. The
      development of OICC in 80% of the patients was associated with exacerbation of
      chronic suppurative otitis media; in the remaining 20% of the patients OICC were
      the consequences of acute suppurative otitis media. Thrombosis of sigmoid sinus
      as an independent otogenic intracranial complication was documented in 17.5% of
      the patients while 42.5% of the cases required the treatment by an
      interdisciplinary team of specialists with the participation of an
      otorhinolaryngologist, neurologist, intensive care and other professionals. Such
      approach partly accounts for the relatively low (10.6%) mortality rate among our
      patients with OICC.

PMID- 27876727
TI  - [Specific immunotherapy applied in the otorhionolaryngological practice].
AB  - The objective of the present study was to formulate the indications for the
      specific immunotherapy (SIT) of ENT diseases based on the results of the
      examination and treatment of 1058 patients presenting with allergic rhinitis with
      special reference to the advantages of this approach over pharmacotherapy. Much
      attention is given to the adverse reactions associated with the application of
      immunotherapy and the methods for their correction. Personal opinions of the
      authors with regard to selected aspects of the use of specific immunotherapy in
      the otorhionolaryngological practice are presented.

PMID- 27876728
TI  - [Mucoviscidosis, a challenging medical problem].
AB  - The authors present the currently available data on mucoviscidosis (cystic
      fibrosis) based on their original experience and the review of the relevant
      literature. Special attention is given to the pathogenetic mechanisms underlying
      the development of this condition, its diagnostics, and methods of treatment as
      exemplified by the clinical case of cystic fibrosis in an adult patient.

PMID- 27876729
TI  - [Zivert-Kartagener's syndrome encountered in the practical work of an
      otorhionolaryngologist, pulmonologist, obstetrician, and gynecologist].
AB  - The objective of the present work was to analyze the current concept of the
      genetically predetermined condition Zivert-Kartagener's syndrome with special
      reference to the pathogenetic mechanisms underlying the development of this
      condition, its clinical picture and methods of treatment. The authors' original
      observations of the patients presenting with Zivert-Kartagener's syndrome are
      reported.

PMID- 27876730
TI  - [The analysis of 42 observations of paranasal sinus osteoma].
AB  - The data on the incidence, localization, and histological structure of paranasal
      sinus osteoma (PSO) are reported along with the authors' experience in the
      diagnostics and surgical treatment of 42 patients presenting with this condition.
      The classification of the remote tumours based on their histopathological
      characteristics is considered. It is shown that 34 (80.9%) patients have osteomas
      of the compact type, 4 (9.5%) present with the tumours of the spongy type, and
      another 4 (9.5%) with the mixed type osteomas. It is maintained that the
      application of boron should be considered to facilitate the surgical removal of
      paranasal sinus osteomas.

PMID- 27876731
TI  - [Congenital cysts and fistulas on the neck].
AB  - This paper presents the currently available data on congenital lateral cysts and
      fistulas of the neck based on the authors' original experience and the review of
      the relevant literature. The modern methods for diagnostics and the surgical
      treatment of these conditions are described and the causes underling the
      development of their relapses are analyzed. Recommendations for the prevention of
      congenital cysts and fistulas on the neck are proposed.

PMID- 27876732
TI  - [The use of propolis-based therapy in otorhionolaryngology].
AB  - The authors analyze the literature publications and the results of their original
      investigations concerning the application of the propolis-based pharmacological
      products for the treatment of acute and chronic diseases of the upper respiratory
      tract and ears. The desirability of the more extensive application of the
      propolis-containing medicines in the routine otorhinolaryngological practice is
      emphasized bearing in mind their numerous biological effects including
      antibiotic, anti-inflammatory, immunostimulating, anti-oxidative, anesthetic, and
      cytostatic actions.

PMID- 27876733
TI  - [A rare observation of intralaryngeal aberrant goiter].
AB  - This paper was designed to report a rare observation of intralaryngeal aberrant
      goiter associated with goiter of the main thyroid tissue and chronic suppurative
      otitis media complicated by the polyp that causes occlusion of the auditory
      passage. The histomorphological investigation of the material harvested
      intraoperatively following rehabilitation of the purulent focus in the middle ear
      and the removal of the tumour from the inside of the right vestibular fold
      confirmed the diagnosis of colloid goiter.

PMID- 27876734
TI  - [About the unresolved problems of terminology and classification of allergic
      rhinitis and the desirability of distinguishing the mixed form of the disease].
AB  - This article deals with the history of the development of terminology and
      classification of allergic (vasomotor) rhinitis during the last 50 years.

PMID- 27876735
TI  - [The basic principles underlying the provision of the urgent and emergency
      medical assistance in otorhionolaryngology].
AB  - The peculiarities of the clinical course of ENT pathologies are considered with
      special reference to the associated life-threatening conditions. The basic
      principles underlyi ng the provision of the urgent and emergency medical
      assistance in the otorhionolaryngological practice are discussed.

PMID- 27876736
TI  - [The speech audiometry using the matrix sentence test].
AB  - The matrix sentence test in which the five-word semantically unpredictable
      sentences presented under the background noise conditions are used as the speech
      material was designed and validated for many languages. The objective of the
      present study was to evaluate the Russian version of the matrix sentence test
      (RuMatrix test) in the listeners of different ages with normal hearing. At the
      first stage of the study, 35 listeners at the age from 18 to 33 year were
      examined. The results of the estimation of the training effect dictated the
      necessity of conducting two training tracks before carrying out the RuMatrix test
      proper. The signal-to-noise ratio at which 50% speech recognition (SRT50) was
      obtained was found to be -8.8+/-0.8 dB SNR. A significant effect of exposure to
      the background noise was demonstrated: the noise level of 80 and 75 Db SPL led to
      a considerably lower intelligibility than the noise levels in the range from 45
      to 70 dB SPL; in the subsequent studies, the noise level of 65 dB SPL was used.
      The high test-retest reliability of the RuMatrix test was proved. At the second
      stage of the study, 20 young (20-40 year old) listeners and 20 aged (62-74 year
      old) ones were examined. The mean SRT50 in the aged patients was found to be 
      6.9+/-1.1 dB SNR which was much worse than the mean STR50 in the young subjects (
      8.7+/-0.9 dB SNR). It is concluded that, bearing in mind the excellent
      comparability of the results of the RUMat rix test across different languages, it
      can be used as a universal tool in international research projects.

PMID- 27876737
TI  - [The occupational risk of hearing impairment associated with cardiovascular
      pathologies in the subjects engaged in 'noisy' industries].
AB  - The objective of the present study was to analyze the structure of concomitant
      somatic pathology in the subjects experiencing the occupational hearing problems.
      The study demonstrated the increase in the frequency of concomitant chronic
      diseases and the prevalence of polynosological conditions with the increasing
      severity of hearing impairment. It was shown that cardiovascular pathologies tend
      to enhance the risk of hearing loss in the employees engaged in "noisy"
      occupations. The cause-and-effect relationships were elucidated as the
      contribution of the "vascular" factor to the formation of occupational pathology
      of the organs of hearing. The clinical audilogical features of co-morbid
      occupational hearing impairment associated with vascular pathology were
      characterized by the accelerated development and progression of the hearing
      disorders with the gradual disappearance of the audiological signs characteristic
      of noise-induced lesions.

PMID- 27876738
TI  - [Treatment with the use of microcurrent lymphatic drainage physiotherapy during
      the postoperative period following rhinoplastic surgery].
AB  - The objective of the present study was to evaluate the effectiveness of the
      combined treatment of the patients who had undergone either primary or secondary
      rhinoplastic surgery with the use of photo- and magnetic therapy in comparison
      with the effectiveness of phototherapy in the combination with microcurrent
      therapy. The patients were divided into four groups depending on the type of the
      surgical intervention and the mode of the combined physiotherapeutic treatment.
      All the patients were given combined physiotherapeutic treatment in addition to
      the standard pharmacotherapy starting from the second day of the postoperative
      period. The patients of groups 1 and 3 received phototherapy in the combination
      with magnetic therapy while those in groups 2 and 4 were treated by phototherapy
      in the combination with microcurrent lymphatic drainage physiotherapy. It was
      shown that the different combinations of physiotherapeutic modalities during the
      postoperative period following primary "closed" rhinoplasty were not different
      significantly in terms of effectiveness. After secondary "closed" rhinoplasty,
      the combination of phototherapy with the application of microcurrents looks more
      preferable. It is concluded that microcurrent lymphdraining physiotherapy should
      be regarded as the priority component of the combined physiotherapeutic treatment
      during the postoperative period following secondary "closed" rhinoplasty.

PMID- 27876740
TI  - [The application of the biologically compatible cyanacrylate-based glue for
      ossiculoplasty in the patients presenting with chronic otitis media].
AB  - The objective of the study was to improve the functional outcomes of the
      treatment in the patients presenting with chronic otitis media by means of the
      combined application of platelet-enriched plasma and the biologically compatible
      cyanacrylate-based glue for the fixation of the reconstructed auditory ossicular
      chain. The functional results of the surgery were evaluated within 1, 3, and12
      months after the intervention making use of tonal threshold audiometry. It was
      shown that the use of the platelet-enriched plasma with its subsequent fixation
      by the biologically compatible cyanacrylate-based glue enhances stability of the
      implanted prosthetic elements, reduces the risk of their displacement during the
      postoperative period due to the formation of the cicatrical tissue between the
      structural components of the middle ear. This approach improves the functional
      result of the described treatment and decreases the frequency of relapses
      associated with poor stability of the reconstructed sound-conducting system.

PMID- 27876739
TI  - [The state of the nasal mucosa and the paranasal sinuses in the late
      postoperative period following radical and minimally invasive surgery].
AB  - We have investigated the functional state of the mucous membrane of the nasal
      cavity and maxillary sinus after radical and minimally invasive surgical
      procedures during the log-term postoperative period, i.e. three and more months
      after the intervention. The materials for the study were brushings and
      histological biopsies; in addition, the functional parameters of the mucous
      membranes of the nose and maxillary sinuses were estimated before and after
      surgery. It has been found that the type of the surgical intervention on the
      inferior turbinate bones for the treatment of chronic rhinitis, such as gentle
      turbinotomy, has no significant influence on the state of the mucous membrane.
      The study has demonstrated that 48% of the patients presenting with the chronic
      maxilloethmoidal mixed form of sinusitis experience epithelial metaplasia
      resulting in atrophic scarring of the mucosa whereas in the remaining 52% the
      ciliary epithelium becomes either damaged or detached and the ciliary beat
      frequency (CBF) decreases. In the exudative form of the disease, CBF and some
      other functional characteristics are improved but the stromal oedema persists and
      ciliated epithelium integrity gets compromised.

PMID- 27876741
TI  - [The use of intranasal glucocorticosteroids in the treatment of rhinosinusitis:
      Focus on mometasone furoate].
AB  - The authors discuss the mechanism of action, effectiveness, and safety of
      intranasal glucocorticosteroids (inGCS) used to treat acute, recurrent and
      chronic rhinosinusitis (RS). The last version of the European guidelines
      concerning the application of inGCS assigns the highest level of evidence-Ia and
      the highest strength of recommendations-A to these medications when applied for
      the treatment of acute and polypoid rhinosinusitis. Moreover, they acquire the
      status of the agents of choice for the therapy of chronic RS without polyps.
      Mometasone furoate is one of the best explored preparations of this group of
      medicines. It is possessed of favourable pharmacodynamic and pharmacokinetic
      properties when prescribed for local application. The new mometasone furoate
      preparation in the form of an intranasal spray Dezrinit produced by "Teva" Ltd.
      was registered in the Russian Federation. In a comparative randomized clinical
      trial (RCT), the preparation was shown to be an equivalent to the Nasonex spray.

PMID- 27876742
TI  - [On the problem of voice rehabilitation in the case of unilateral vocal fold
      paresis].
AB  - BACKGROUND: Unilateral vocal fold paresis (UVFP) significantly deteriorates the
      patient's quality of life. The leading role in the rehabilitation of the patients
      presenting with UVFP belongs to stimulation therapy which consists in the
      activation of muscle re-innervation of the larynx and the compensatory mechanisms
      allowing to achieve the most complete closure of the vocal folds during
      phonation. AIM: The objective of the present study was the optimization of the
      conservative treatment of patients with UVFP. MATERIAL AND METHODS: Fifty
      patients at the age varying from 18 to 70 years presenting with UVFP (the
      duration of the disease less than 6 months underwent the comprehensive treatment
      including electrostimulation of the larynx, vitamin therapy, and speech therapy.
      The patients were divided into two groups: A and B comprised of 25 subjects each.
      Those of Group A were given, in addition to the standard treatment, a 1.5 month
      long course of Neuromidin therapy. The results of the treatment were evaluated
      with the use of laryngostroboscopy, flowmetry, the GRBAS scale, acoustic voice
      analysis (lingWaves), and the VHI questionnaire. RESULTS: The restoration of
      vocal fold mobility was achieved in 20% and 8% of the patients of groups A and B
      respectively. The clinical effect was absent in 12% of the patients in Group A
      and 28% of the patients in Group B. The differences between groups were
      statistically significant (p<0.05). In the remaining cases, the positive dynamics
      of the flowmetric characteristics, GRBAS and VHI data, maximum phonation time,
      Jitter, DSI, frequency and dynamic ranges as well as the intensity of voice were
      documented in 68% of patients in Group A and 64% of patients in Group B).
      CONCLUSION: The results of the study confirm the usefulness of the combined
      treatment of UVFP consisting of electrostimulation of the larynx together with
      speech therapy and application of cholinergic drugs. The addition of Neuromidin
      to the conventional scheme of conservative treatment can further improve its
      efficiency from 72% to 88%.

PMID- 27876743
TI  - [The possibilities for the rational pharmacotherapy of adenoiditis in the
      children].
AB  - The available literature data give evidence that viral infection is the main
      cause underlying the development of inflammatory nasopharyngeal pathology in the
      children. According to ICD-10, nether acute nor chronic adenoiditis should be
      considered as a self-consistent nosological entity. Acute adenoiditis is usually
      regarded as a form of acute nasopharyngitis (J02) or acute respiratory viral
      infection (J06.9) whereas chronic adenoiditis is commonly referred to as
      representing other chronic diseases of the tonsils and adenoids (J 35.8). The
      reactive changes in the nasopharyngeal tonsils begin to be manifested on days 3-5
      after the onset of acute respiratory viral infection; thereafter, they persist
      and gradually disappear within the next 2-3 weeks. In the majority of the cases,
      acute adenoiditis is actually a physiological reaction of the nasopharyngeal
      tonsils as the organs of regional mucosal immunity to antigenic stimulation.
      There is no universally accepted opinion as regards the duration of the
      inflammatory process which would allow these pathological changes to be
      considered as turned into chronic ones. This condition is actually not a serious
      pathology provided it is not associated with the concomitant complications and
      produces no clinically significant effect on the child's quality of life. Under
      practical conditions, such children are most frequently treated with the use of
      irrigation therapy. Taking into account that otorhinolaryngologists all over the
      world do not consider chronic adenoiditis as an independent nosological entity
      but distinguish only hypertrophy of adenoid vegetations or chronic rhinosinusitis
      (in the presence of inflammatory changes in the nasopharynx), it appears correct
      to speak about chronic adenoiditis provided the clinical manifestations of the
      disease persist for more than 12 weeks. Based on the predominant etiological
      component, the viral, bacterial, and allergic forms of nasopharyngeal adenoiditis
      can be distinguished even though it is rather difficult to actually determine
      which etiological factor prevails in each concrete case. The aforedescribed
      situation poses a large number of questions pertaining to the choice of either
      systemic or topical antibacterial therapy.

PMID- 27876744
TI  - [The nasolabial cyst encountered in the practical work of the
      otorhinolaryngologists].
AB  - Two clinical observations of nasolabial cyst of uni- and bilateral localizations
      are reported. The comprehensive characteristic of nasolabial cysts is presented
      with special reference to the principal diagnostic criteria for this pathology
      and the potential diagnostic errors.

PMID- 27876745
TI  - [Desmoplastic fibroma of the temporal bone].
AB  - This paper reports a case of the extremely rare disease, the desmoplastic fibroma
      of the temporal bone (DF). The clinical course of this pathology, the methods for
      its diagnostics, and surgical treatment are described.

PMID- 27876746
TI  - [The cross-plastic correction of the soft tissue defect on the neck with the use
      of a pectoral flap harvested from the opposite side].
AB  - The authors describe a patient presenting with initially multiple metachronous
      cancer spreading over the right-handed side of the mouth floor and the right
      handed part of the lower jaw. The patient who underwent cross-plastic surgery for
      the correction of the extensive soft tissue defect on the neck with the use of
      the musculocutaneous pectoral flap with the axial blood supply is described. The
      observation during the 14 year follow-up period confirmed the good functional
      outcome of the treatment.

PMID- 27876747
TI  - [A large foreign body (a pin) in the trachea].
AB  - A foreign body is known to be retained in the human trachea only in very rare
      cases, e.g. due to its large size preventing the further passage through the
      glottis into a bronchial tube or because of its specific shape facilitating the
      attachment of the body to the tracheal walls and clamping between them. In this
      paper, the author presents a case of the localization of an unusually large
      foreign body (a pin) in the trachea of a 14 year old child.

PMID- 27876748
TI  - Driving Pest Insect Populations: Agricultural Chemicals Lead to an Adaptive
      Syndrome in Nilaparvata Lugens Stal (Hemiptera: Delphacidae).
AB  - The brown planthopper (BPH) is a devastating pest of rice throughout Asia. In
      this paper we document the BPH biogeographic range expansion in China over the 20
      year period, 1992 to 2012. We posed the hypothesis that the range expansion is
      due to a syndrome of adaptations to the continuous presence of agricultural
      chemicals (insecticides and a fungicide) over the last 40 years. With respect to
      biogeography, BPH ranges have expanded by 13% from 1992 to 1997 and by another 3%
      from 1997 to 2012. In our view, such expansions may follow primarily from the
      enhancing effects of JGM, among other agricultural chemicals, and from global
      warming. JGM treatments led to increased thermotolerance, recorded as decreased
      mortality under heat stress at 40 +/- 1  degrees C (down from 80% to 55%) and
      increased fecundity (by 49%) at 34  degrees C. At the molecular level, JGM
      treatments led to increased abundances of mRNA encoding Acetyl Co-A carboxylase
      (Acc) (up 25%) and Hsp70 (up 32%) in experimental BPH. RNAi silencing of Hsp70
      and Acc eliminated the JGM effects on fecundity and silencing Hsp70 reduced JGM
      induced thermotolerance. Integrated with global climate change scenarios, such
      syndromes in pest insect species have potential for regional- and global-scale
      agricultural disasters.

PMID- 27876749
TI  - Anti-fungal activity of Ctn[15-34], the C-terminal peptide fragment of
      crotalicidin, a rattlesnake venom gland cathelicidin.
AB  - Crotalicidin (Ctn), a 34-residue cathelicidin from a South American rattlesnake,
      and its fragment (Ctn[15-34]) have shown anti-infective and cytotoxic activities
      against Gram-negative bacteria and certain tumor lines, respectively. The extent
      of such effects has been related to physicochemical characteristics such as
      helicity and hydrophobicity. We now report the anti-fungal activity of Ctn and
      its fragments (Ctn[1-14]) and (Ctn[15-34]). MIC determination and luminescent
      cell viability assays were used to evaluate the anti-infective activity of Ctn
      and its fragments (Ctn[1-14]) and (Ctn[15-34]) as anti-fungal agents against
      opportunistic yeast and dermatophytes. Cytotoxicity towards healthy eukaryotic
      cells was assessed in vitro with healthy human kidney-2 (HK-2) cells and
      erythrocytes. The checkerboard technique was performed to estimate the effects of
      combining either one of the peptides with amphotericin B. Ctn was the most active
      peptide against dermatophytes and also the most toxic to healthy eukaryotic
      cells. Fragments Ctn[1-14] and Ctn[15-35] lost activity against dermatophytes,
      but became more active against pathogenic yeasts, including several Candida
      species, both clinical isolates and standard strains, with MICs as low as 5 MUm.
      Interestingly, the two peptide fragments were less cytotoxic to healthy HK-2
      cells and less hemolytic to human erythrocytes than the standard-of-care
      amphotericin B. Also noteworthy was the synergy between Ctn peptides and
      amphotericin B, with consequent reduction in MICs of both drug and peptides.
      Altogether, Ctn and its fragments, particularly Ctn[15-34], are promising leads,
      either alone or in combined regimen with amphotericin B, for the treatment of
      fungal diseases.

PMID- 27876750
TI  - 8'-epimer of herbicidin F and its congeners from Streptomyces sp. YIM 66142.

PMID- 27876751
TI  - Cell mechanotransduction: Stretch to express.

PMID- 27876752
TI  - Suprapowered nanomachines.

PMID- 27876753
TI  - Metamaterials: Prime time.

PMID- 27876754
TI  - Magnetic skyrmions: Particles or waves.

PMID- 27876755
TI  - Nanocrystal superlattices: The pathway to atomic alignment.

PMID- 27876756
TI  - Oxide interfaces: Spin-to-charge current conversion.

PMID- 27876757
TI  - Material Witness: A jammy guess?

PMID- 27876758
TI  - Improving the characterization of dissolved organic carbon in cloud water: Amino
      acids and their impact on the oxidant capacity.
AB  - Improving our understanding of cloud chemistry depends on achieving better
      chemical characterization (90% of the organic carbon [OC] fraction remains
      uncharacterized) and, consequently, assessing the reactivity of this complex
      system. In this manuscript, we report for the first time the concentrations of 16
      amino acids (AAs) in 25 cloud water samples. The concentrations of individual AAs
      ranged from a few nM up to ~2.0 MUM, and the average contribution of AAs
      corresponded to 9.1% (4.4 to 21.6%) of the dissolved OC (DOC) concentration.
      Considering their occurrence and concentrations, AAs were expected to represent
      an important hydroxyl radical (HO*) sink in aqueous cloud samples. In this work,
      we estimated that approximately 17% (from 7 to 36%) of the hydroxyl radical
      scavenging ability of the DOC could be attributed to the presence of AAs, whereas
      comparing the AAs suggested that an average of 51% (from 22 to 80%) of their
      reactivity with HO* could account for the presence of tryptophan. These results
      clearly demonstrate that the occurrence and reactivity of AAs must be considered
      to better estimate the chemical composition and oxidant capacity of the cloud
      aqueous phase.

PMID- 27876759
TI  - Vertical flow array chips reliably identify cell types from single-cell mRNA
      sequencing experiments.
AB  - Single-cell mRNA sequencing offers an unbiased approach to dissecting cell types
      as functional units in multicellular tissues. However, highly reliable cell
      typing based on single-cell gene expression analysis remains challenging because
      of the lack of methods for efficient sample preparation for high-throughput
      sequencing and evaluating the statistical reliability of the acquired cell types.
      Here, we present a highly efficient nucleic reaction chip (a vertical flow array
      chip (VFAC)) that uses porous materials to reduce measurement noise and improve
      throughput without a substantial increase in reagent. We also present a
      probabilistic evaluation method for cell typing depending on the amount of
      measurement noise. Applying the VFACs to 2580 monocytes provides 1967 single-cell
      expressions for 47 genes, including low-expression genes such as transcription
      factors. The statistical method can distinguish two cell types with probabilistic
      quality values, with the measurement noise level being considered for the first
      time. This approach enables the identification of various sub-types of cells in
      tissues and provides a foundation for subsequent analyses.

PMID- 27876760
TI  - Changes of bivalent chromatin coincide with increased expression of developmental
      genes in cancer.
AB  - Bivalent (poised or paused) chromatin comprises activating and repressing histone
      modifications at the same location. This combination of epigenetic marks at
      promoter or enhancer regions keeps genes expressed at low levels but poised for
      rapid activation. Typically, DNA at bivalent promoters is only lowly methylated
      in normal cells, but frequently shows elevated methylation levels in cancer
      samples. Here, we developed a universal classifier built from chromatin data that
      can identify cancer samples solely from hypermethylation of bivalent chromatin.
      Tested on over 7,000 DNA methylation data sets from several cancer types, it
      reaches an AUC of 0.92. Although higher levels of DNA methylation are often
      associated with transcriptional silencing, counter-intuitive positive statistical
      dependencies between DNA methylation and expression levels have been recently
      reported for two cancer types. Here, we re-analyze combined expression and DNA
      methylation data sets, comprising over 5,000 samples, and demonstrate that the
      conjunction of hypermethylation of bivalent chromatin and up-regulation of the
      corresponding genes is a general phenomenon in cancer. This up-regulation affects
      many developmental genes and transcription factors, including dozens of homeobox
      genes and other genes implicated in cancer. Thus, we reason that the disturbance
      of bivalent chromatin may be intimately linked to tumorigenesis.

PMID- 27876762
TI  - The stable microbiome of inter and sub-tidal anemone species under increasing
      pCO2.
AB  - Increasing levels of pCO2 within the oceans will select for resistant organisms
      such as anemones, which may thrive under ocean acidification conditions. However,
      increasing pCO2 may alter the bacterial community of marine organisms,
      significantly affecting the health status of the host. A pH gradient associated
      with a natural volcanic vent system within Levante Bay, Vulcano Island, Italy,
      was used to test the effects of ocean acidification on the bacterial community of
      two anemone species in situ, Anemonia viridis and Actinia equina using 16 S rDNA
      pyrosequencing. Results showed the bacterial community of the two anemone species
      differed significantly from each other primarily because of differences in the
      Gammaproteobacteria and Epsilonproteobacteria abundances. The bacterial
      communities did not differ within species among sites with decreasing pH except
      for A. viridis at the vent site (pH = 6.05). In addition to low pH, the vent site
      contains trace metals and sulfide that may have influenced the bacteria community
      of A. viridis. The stability of the bacterial community from pH 8.1 to pH 7.4,
      coupled with previous experiments showing the lack of, or beneficial changes
      within anemones living under low pH conditions indicates that A. viridis and A.
      equina will be winners under future ocean acidification scenarios.

PMID- 27876761
TI  - Early infant adipose deposition is positively associated with the n-6 to n-3
      fatty acid ratio in human milk independent of maternal BMI.
AB  - BACKGROUND/OBJECTIVES: Excessive infant weight gain in the first 6-month of life
      is a powerful predictor of childhood obesity and related health risks. In mice,
      omega-6 fatty acids (FAs) serve as potent ligands driving adipogenesis during
      early development. The ratio of omega-6 relative to omega-3 (n-6/n-3) FA in human
      milk (HM) has increased threefold over the last 30 years, but the impact of this
      shift on infant adipose development remains undetermined. This study investigated
      how maternal obesity and maternal dietary FA (as reflected in maternal red blood
      cells (RBCs) composition) influenced HM n-6 and n-3 FAs, and whether the HM n-6/n
      3 ratio was associated with changes in infant adipose deposition between 2 weeks
      and 4 months postpartum. SUBJECTS/METHODS: Forty-eight infants from normal weight
      (NW), overweight (OW) and obese (OB) mothers were exclusively or predominantly
      breastfed over the first 4 months of lactation. Mid-feed HM and maternal RBC were
      collected at either transitional (2 weeks) or established (4 months) lactation,
      along with infant body composition assessed using air-displacement
      plethysmography. The FA composition of HM and maternal RBC was measured
      quantitatively by lipid mass spectrometry. RESULTS: In transitional and
      established HM, docosahexaenoic acid (DHA) was lower (P=0.008; 0.005) and the
      arachidonic acid (AA)/DHA+eicosapentaenoic acid (EPA) ratio was higher (P=0.05;
      0.02) in the OB relative to the NW group. Maternal prepregnancy body mass index
      (BMI) and AA/DHA+EPA ratios in transitional and established HM were moderately
      correlated (P=0.018; 0.001). Total infant fat mass was increased in the upper
      AA/DHA+EPA tertile of established HM relative to the lower tertile (P=0.019). The
      amount of changes in infant fat mass and percentage of body fat were predicted by
      AA/EPA+DHA ratios in established HM (P=0.038; 0.010). CONCLUSIONS: Perinatal
      infant exposures to a high AA/EPA+DHA ratio during the first 4 months of life,
      which is primarily reflective of maternal dietary FA, may significantly
      contribute to the way infants accumulate adipose.

PMID- 27876764
TI  - Seep-carbonate lamination controlled by cyclic particle flux.
AB  - Authigenic carbonate build-ups develop at seafloor methane-seeps, where
      microbially mediated sulphate-dependent anaerobic oxidation of methane
      facilitates carbonate precipitation. Despite being valuable recorders of past
      methane seepage events, their role as archives of atmospheric processes has not
      been examined. Here we show that cyclic sedimentation pulses related to the
      Indian monsoon in concert with authigenic precipitation of methane-derived
      aragonite gave rise to a well-laminated carbonate build-up within the oxygen
      minimum zone off Pakistan (northern Arabian Sea). U-Th dating indicates that the
      build-up grew during past ~1,130 years, creating an exceptional high-resolution
      archive of the Indian monsoon system. Monsoon-controlled formation of seep
      carbonates extends the known environmental processes recorded by seep-carbonates,
      revealing a new relationship between atmospheric and seafloor processes.

PMID- 27876763
TI  - Growth factor and co-receptor release by structural regulation of substrate
      metalloprotease accessibility.
AB  - Release of cytokines, growth factors and other life-essential molecules from
      precursors by a-disintegrin-and-metalloproteases (ADAMs) is regulated with high
      substrate-specificity. We hypothesized that this is achieved by cleavage
      regulatory intracellular-domain (ICD)-modifications of the precursors. We show
      here that cleavage-stimuli-induced specific ICD-modifications cause structural
      substrate changes that enhance ectodomain sensitivity of neuregulin-1 (NRG1;
      epidermal-growth-factor) or CD44 (receptor-tyrosine-kinase (RTK) co-receptor) to
      chymotrypsin/trypsin or soluble ADAM. This inside-out signal transfer required
      substrate homodimerization and was prevented by cleavage-inhibitory ICD
      mutations. In chimeras, regulation could be conferred to a foreign ectodomain,
      suggesting a common higher-order structure. We predict that substrate-specific
      protease-accessibility-regulation controls release of numerous ADAM substrates.

PMID- 27876766
TI  - Hot electron induced non-saturation current behavior at high electric field in
      InAlN/GaN heterostructures with ultrathin barrier.
AB  - The high-field transport characteristics of nearly lattice-matched InAlN/GaN
      heterostructures with different barrier thickness were investigated. It is found
      that the current in the InAlN/GaN heterostructures with ultrathin barrier shows
      unsaturated behaviors (or secondary rising) at high voltage, which is different
      from that of AlGaN/GaN heterostructures. This phenomenon is more obvious if the
      barrier thickness is thinner and the channel width is narrower. The experimental
      results demonstrate that it is the increasing carrier density excited from the
      more defect states by the hot electrons with larger electron saturation velocity
      that results in the unsaturated current behaviors in InAlN/GaN heterostructures.
      Our results pave a way for further optimizing InAlN barrier design and improving
      the reliability of InAlN/GaN HEMTs.

PMID- 27876768
TI  - Gut microbiota: Culturomics: illuminating microbial dark matter.

PMID- 27876767
TI  - 14,000-year-old seeds indicate the Levantine origin of the lost progenitor of
      faba bean.
AB  - The understanding of crop domestication is dependent on tracking the original
      geographical distribution of wild relatives. The faba bean (Vicia faba L.) is
      economically important in many countries around the world; nevertheless, its
      origin has been debated because its ancestor could not be securely identified.
      Recent investigations in the site of el-Wad (Mount Carmel, Israel), provide the
      first and, so far, only remains of the lost ancestor of faba bean. X-ray CT scan
      analysis of the faba beans provides the first set of measurements of the biometry
      of this species before its domestication. The presence of wild specimens in Mount
      Carmel, 14,000 years ago, supports that the wild variety grew nearby in the Lower
      Galilee where the first domestication was documented for Neolithic farmers 10,200
      years ago.

PMID- 27876765
TI  - Pre- and post-weaning diet alters the faecal metagenome in the cat with
      differences in vitamin and carbohydrate metabolism gene abundances.
AB  - Dietary format, and its role in pet nutrition, is of interest to pet food
      manufacturers and pet owners alike. The aim of the present study was to
      investigate the effects of pre- and post-weaning diets (kibbled or canned) on the
      composition and function of faecal microbiota in the domestic cat by shotgun
      metagenomic sequencing and gene taxonomic and functional assignment using MG
      RAST. Post-weaning diet had a dramatic effect on community composition; 147 of
      the 195 bacterial species identified had significantly different mean relative
      abundances between kittens fed kibbled and canned diets. The kittens fed kibbled
      diets had relatively higher abundances of Lactobacillus (>100-fold),
      Bifidobacterium (>100-fold), and Collinsella (>9-fold) than kittens fed canned
      diets. There were relatively few differences in the predicted microbiome
      functions associated with the pre-weaning diet. Post-weaning diet affected the
      abundance of functional gene groups. Genes involved in vitamin biosynthesis,
      metabolism, and transport, were significantly enriched in the metagenomes of
      kittens fed the canned diet. The impact of post-weaning diet on the metagenome in
      terms of vitamin biosynthesis functions suggests that modulation of the
      microbiome function through diet may be an important avenue for improving the
      nutrition of companion animals.

PMID- 27876770
TI  - Tumour metabolism: RED(D1) or dead.

PMID- 27876771
TI  - Tumour metabolism: When metabolic and epigenetic states converge.

PMID- 27876772
TI  - Angiogenesis: Going with the flow.

PMID- 27876773
TI  - Immunotherapy: Powerful combinations.

PMID- 27876774
TI  - Anticancer drugs: Breaking up a pro-survival interaction.

PMID- 27876769
TI  - Gastrointestinal aspects of vasculitides.
AB  - Systemic vasculitides are caused by inflammation of blood vessels and can affect
      any organ and any part of the gastrointestinal tract, hepatic and biliary system,
      as well as the pancreas. These disorders can cause a wide array of
      gastrointestinal manifestations, from asymptomatic elevated transaminase levels
      and mild abdominal pain to potentially life-threatening bowel perforations and
      peritonitis. A diagnosis based solely on gastrointestinal symptoms is challenging
      as these manifestations are not specific. Conversely, diagnostic and therapeutic
      delays can be rapidly detrimental. In this article, we review the epidemiology,
      characteristics and management of the main gastrointestinal manifestations of
      systemic vasculitides, including polyarteritis nodosa and antineutrophil
      cytoplasm antibody-associated vasculitides, as well as isolated vasculitides
      limited to the gastrointestinal tract.

PMID- 27876775
TI  - Tumour immunology: The consequences of concomitant challenges.

PMID- 27876777
TI  - Cancer risk: Generating tumours: it's all in the balance.

PMID- 27876776
TI  - Metastasis: Caught in a trap.

PMID- 27876779
TI  - Mutational landscape in children with myelodysplastic syndromes is distinct from
      adults: specific somatic drivers and novel germline variants.

PMID- 27876778
TI  - Differential fecal microbiota are retained in broiler chicken lines divergently
      selected for fatness traits.
AB  - Our study combined 16S rRNA-pyrosequencing and whole genome sequencing to analyze
      the fecal metagenomes of the divergently selected lean (LL) and fat (FL) line
      chickens. Significant structural differences existed in both the phylogenic and
      functional metagenomes between the two chicken lines. At phylum level, the FL
      group had significantly less Bacteroidetes. At genus level, fourteen genera of
      different relative abundance were identified, with some known short-chain fatty
      acid producers (including Subdoligranulum, Butyricicoccus, Eubacterium,
      Bacteroides, Blautia) and a potentially pathogenic genus (Enterococcus).
      Redundancy analysis identified 190 key responsive operational taxonomic units
      (OTUs) that accounted for the structural differences between the phylogenic
      metagenome of the two groups. Four Cluster of Orthologous Group (COG) categories
      (Amino acid transport and metabolism, E; Nucleotide transport and metabolism, F;
      Coenzyme transport and metabolism, H; and Lipid transport and metabolism, I) were
      overrepresented in LL samples. Fifteen differential metabolic pathways
      (Biosynthesis of amino acids, Pyruvate metabolism, Nitrotoluene degradation,
      Lipopolysaccharide biosynthesis, Peptidoglycan biosynthesis, Pantothenate and CoA
      biosynthesis, Glycosaminoglycan degradation, Thiamine metabolism,
      Phosphotransferase system, Two-component system, Bacterial secretion system,
      Flagellar assembly, Bacterial chemotaxis, Ribosome, Sulfur relay system) were
      identified. Our data highlighted interesting variations between the gut
      metagenomes of these two chicken lines.

PMID- 27876780
TI  - A Meta-analysis of MBL2 Polymorphisms and Tuberculosis Risk.
AB  - MBL2 gene encodes mannose-binding lectin, is a member of innate immune system.
      Earlier studies revealed that MBL2 gene variants, rs1800451, rs1800450,
      rs5030737, rs7096206, rs11003125 and rs7095891 are associated with impaired serum
      level and susceptibility to TB, but their results are inconsistent. A meta
      analysis was performed by including 22 studies (7095 TB-patients and 7662
      controls) and data were analyzed with respect to associations between alleles,
      genotypes and minor allele carriers to evaluate the potential association between
      MBL2 polymorphisms and TB risk. Statistically significant results were found only
      for the homozygous variant genotype (CC vs. AA: p = 0.045; OR = 0.834, 95% CI =
      0.699 to 0.996) of rs1800451 and showed reduced risk of TB in overall population.
      However, other genetic models of rs1800450, rs5030737, rs7096206, rs11003125,
      rs7095891 and combined rs1800450, rs1800451, rs5030737 polymorphisms of MBL2 gene
      did not reveal any association with TB risk. Stratified analysis by ethnicity
      showed decreased risk of TB in African population for rs1800450 and rs1800451.
      Whereas, no association was observed between other MBL2 polymorphisms and TB risk
      in all the evaluated ethnic populations. In conclusion, MBL2 rs1800450 and
      rs1800451 polymorphisms play a protective role in TB infection and reinforce
      their critical significance as a potential genetic marker for TB resistance.

PMID- 27876781
TI  - First identification of NDM-4-producing Escherichia coli ST410 in China.

PMID- 27876783
TI  - Genetic characterization of novel fowl aviadenovirus 4 isolates from outbreaks of
      hepatitis-hydropericardium syndrome in broiler chickens in China.
AB  - Since May 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS)
      associated with infections of fowl aviadenovirus (FAdV) have emerged in broiler
      chickens in several Chinese provinces. To identify the genotype and gain a better
      understanding of the genetic properties of the FAdV strains responsible for the
      recent HHS outbreaks in China, the complete genome sequences of five isolates
      from outbreaks of HHS in broiler chickens in five provinces were determined. The
      results demonstrated that a novel fowl aviadenovirus 4 (FAdV-4) genotype was
      epidemic in China. To investigate the molecular characteristics of these Chinese
      FAdV-4 isolates, their genome contents were compared with those of reported
      pathogenic and non-pathogenic FAdV-4 strains. The comparative analysis revealed
      that the novel Chinese FAdV-4 isolates contain various genomic deletions and
      multiple distinct amino-acid mutations in their major structural genes. Two
      additional putative genetic virulence markers in the fiber 2 gene were
      identified. These findings confirmed some of the genetic differences between the
      pathogenic and non-pathogenic FAdV-4 isolates. The data presented in this report
      will enhance the current understanding of the molecular epidemiology and genetic
      diversity of FAdV-4 isolates in China and will provide additional insight into
      the critical factors that determine the pathogenicity of FAdV-4 strains. Finally,
      the emergence of this novel and highly pathogenic FAdV-4 genotype emphasizes that
      preventive measures against FAdV-4 infections on poultry farms should be
      implemented in China.

PMID- 27876782
TI  - Human papillomavirus prevalence and associated factors in women and men in south
      China: a population-based study.
AB  - Oncogenic human papillomavirus (HPV) infection is a cause of many anogenital
      cancers in women and men; however, there is little research on HPV prevalence and
      risk factors that includes both women and men from the same population. A total
      of 4687 participants, including 2378 women and 2309 men aged 18-55 years old from
      the same community, were enrolled in the study in Liuzhou, China. Exfoliated
      cells were collected from the participants from different anatomic sites and were
      tested for 13 oncogenic and 3 non-oncogenic HPV types. The prevalence of any
      oncogenic HPV type was higher in women than in men (18.7% vs 9.4%, P<0.001),
      whereas the prevalence of HPV 6 and 11 infection was similar (1.4% vs 1.2%,
      P=0.6832). HPV 52, 58, 16, 39 and 18 were the five most prevalent types in both
      sexes. Sexual and hygienic behaviors were associated with HPV infection in both
      women and men. We found that oncogenic HPV DNA detection is more prevalent in
      women than in men in China, whereas the prevalence of HPV 6 and 11 is similar in
      both sexes. The data indicate that the interaction of host and virus might be
      different among high- and low-risk HPV types.

PMID- 27876784
TI  - Expression and characterization of a Talaromyces marneffei active phospholipase B
      expressed in a Pichia pastoris expression system.
AB  - Phospholipase B is a virulence factor for several clinically important pathogenic
      fungi, including Candida albicans, Cryptococcus neoformans and Aspergillus
      fumigatus, but its role in the thermally dimorphic fungus Talaromyces marneffei
      remains unclear. Here, we provide the first report of the expression of a novel
      phospholipase gene, designated TmPlb1, from T. marneffei in the eukaryotic
      expression system of Pichia pastoris GS115. Sensitive real-time quantitative
      reverse-transcription PCR (qRT-PCR) demonstrated that the expression of TmPlb1
      increased 1.85-fold in the yeast phase compared with the mycelial phase. TmPlb1
      contains an open reading frame (ORF) of 732 bp that encodes a protein of 243
      amino acids. The conserved serine, aspartate and histidine catalytic triad and
      the G-X-S-X-G domain of TmPLB1 provide the structural basis for its molecular
      activity. The ORF of TmPlb1 was successfully cloned into a pPIC9K vector
      containing an alpha-mating factor secretion signal that allowed the secretory
      expression of TmPLB1 in P. pastoris. The heterologous protein expression began 12
      h after methanol induction and peaked at 96 h. Through analysis with SDS
      polyacrylamide gel electrophoresis (SDS-PAGE), western blotting and mass
      spectrometry, we confirmed that TmPLB1 was successfully expressed. Through Ni
      affinity chromatography, TmPLB1 was highly purified, and its concentration
      reached 240.4 mg/L of culture medium. With specific substrates, the phospholipase
      A1 and phospholipase A2 activities of TmPLB1 were calculated to be 5.96 and 1.59
      U/mg, respectively. The high purity and activity of the TmPLB1 obtained here lay
      a solid foundation for further investigation.

PMID- 27876785
TI  - Characterization of the Annonaceous acetogenin, annonacinone, a natural product
      inhibitor of plasminogen activator inhibitor-1.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of the tissue
      type and urokinase type plasminogen activators. High levels of PAI-1 are
      correlated with an increased risk of thrombotic events and several other
      pathologies. Despite several compounds with in vitro activity being developed,
      none of them are currently in clinical use. In this study, we evaluated a novel
      PAI-1 inhibitor, annonacinone, a natural product from the Annonaceous acetogenins
      group. Annonacinone was identified in a chromogenic screening assay and was more
      potent than tiplaxtinin. Annonacinone showed high potency ex vivo on
      thromboelastography and was able to potentiate the thrombolytic effect of tPA in
      vivo in a murine model. SDS-PAGE showed that annonacinone inhibited formation of
      PAI-1/tPA complex via enhancement of the substrate pathway. Mutagenesis and
      molecular dynamics allowed us to identify annonacinone binding site close to
      helix D and E and beta-sheets 2A.

PMID- 27876786
TI  - A view of human haematopoietic development from the Petri dish.
AB  - Human pluripotent stem cells (hPSCs) provide an unparalleled opportunity to
      establish in vitro differentiation models that will transform our approach to the
      study of human development. In the case of the blood system, these models will
      enable investigation of the earliest stages of human embryonic haematopoiesis
      that was previously not possible. In addition, they will provide platforms for
      studying the origins of human blood cell diseases and for generating de novo
      haematopoietic stem and progenitor cell populations for cell-based regenerative
      therapies.

PMID- 27876788
TI  - Anomalously rotary polarization discovered in homochiral organic ferroelectrics.
AB  - Molecular ferroelectrics are currently an active research topic in the field of
      ferroelectric materials. As complements or alternatives of conventional inorganic
      ferroelectrics, they have been designed to realize various novel properties,
      ranging from multiferroicity and semiconductive ferroelectricity to ferroelectric
      photovoltaics and ferroelectric luminescence. The stabilizing of ferroelectricity
      in various systems is owing to the flexible tailorability of the organic
      components. Here we describe the construction of optically active molecular
      ferroelectrics by introducing homochiral molecules as polar groups. We find that
      the ferroelectricity in (R)-(-)-3-hydroxlyquinuclidinium halides is due to the
      alignment of the homochiral molecules. We observe that both the specific optical
      rotation and rotatory direction change upon paraelectric-ferroelectric phase
      transitions, due to the existence of two origins from the molecular chirality and
      spatial arrangement, whose contributions vary upon the transitions. The optical
      rotation switching effect may find applications in electro-optical elements.

PMID- 27876787
TI  - Deep phenotyping unveils hidden traits and genetic relations in subtle mutants.
AB  - Discovering mechanistic insights from phenotypic information is critical for the
      understanding of biological processes. For model organisms, unlike in cell
      culture, this is currently bottlenecked by the non-quantitative nature and
      perceptive biases of human observations, and the limited number of reporters that
      can be simultaneously incorporated in live animals. An additional challenge is
      that isogenic populations exhibit significant phenotypic heterogeneity. These
      difficulties limit genetic approaches to many biological questions. To overcome
      these bottlenecks, we developed tools to extract complex phenotypic traits from
      images of fluorescently labelled subcellular landmarks, using C. elegans synapses
      as a test case. By population-wide comparisons, we identified subtle but relevant
      differences inaccessible to subjective conceptualization. Furthermore, the models
      generated testable hypotheses of how individual alleles relate to known
      mechanisms or belong to new pathways. We show that our model not only
      recapitulates current knowledge in synaptic patterning but also identifies novel
      alleles overlooked by traditional methods.

PMID- 27876789
TI  - Allostasis in health and food addiction.
AB  - Homeostasis is the basis of modern medicine and allostasis, a further elaboration
      of homeostasis, has been defined as stability through change, which was later
      modified to predictive reference resetting. It has been suggested that pleasure
      is related to salience (behavioral relevance), and withdrawal has been linked to
      allostasis in addictive types. The question arises how the clinical and neural
      signatures of pleasure, salience, allostasis and withdrawal relate, both in a non
      addicted and addicted state. Resting state EEGs were performed in 66 people,
      involving a food-addicted obese group, a non-food addicted obese group and a lean
      control group. Correlation analyses were performed on behavioral data, and
      correlation, comparative and conjunction analyses were performed to extract
      electrophysiological relationships between pleasure, salience, allostasis and
      withdrawal. Pleasure/liking seems to be the phenomenological expression that
      enough salient stimuli are obtained, and withdrawal can be seen as a motivational
      incentive because due to allostatic reference resetting, more stimuli are
      required. In addition, in contrast to non-addiction, a pathological, non-adaptive
      salience attached to food results in withdrawal mediated through persistent
      allostatic reference resetting.

PMID- 27876790
TI  - Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via
      the Mineralocorticoid Receptor.
AB  - Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid
      'habit' memory. In the spatial memory domain, stress impairs place learning
      depending on the hippocampus whereas stimulus-response learning based on the
      striatum appears to be improved. While the neural basis of this shift is still
      unclear, previous evidence in rodents points towards cortisol interacting with
      the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala
      is in turn assumed to orchestrate the stress-induced shift in memory processing.
      However, an integrative study testing these mechanisms in humans is lacking.
      Therefore, we combined functional neuroimaging of a spatial memory task, stress
      induction, and administration of an MR-antagonist in a full-factorial,
      randomized, placebo-controlled between-subjects design in 101 healthy males. We
      demonstrate that stress-induced increases in cortisol lead to enhanced stimulus
      response learning, accompanied by increased amygdala activity and connectivity to
      the striatum. Importantly, this shift was prevented by an acute administration of
      the MR-antagonist spironolactone. Our findings support a model in which the MR
      and the amygdala play an important role in the stress-induced shift towards habit
      memory systems, revealing a fundamental mechanism of adaptively allocating neural
      resources that may have implications for stress-related mental disorders.

PMID- 27876791
TI  - An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal
      epithelial proliferation in mice exposed to radiation.
AB  - Destruction of clonogenic cells in the crypt following irradiation are thought to
      cause altered gastrointestinal function. Previously, we found that an amino acid
      based oral rehydration solution (AA-ORS) improved gastrointestinal function in
      irradiated mice. However, the exact mechanisms were unknown. Electrophysiology,
      immunohistochemistry, qPCR, and Western blot analysis were used to determine that
      AA-ORS increased proliferation, maturation, and differentiation and improved
      electrolyte and nutrient absorption in irradiated mice. A single-hit, multi
      target crypt survival curve showed a significant increase in crypt progenitors in
      irradiated mice treated with AA-ORS for six days (8.8 +/- 0.4) compared to the
      saline-treated group (6.1 +/- 0.3; P < 0.001) without a change in D0 (4.8 +/- 0.1
      Gy). The Dq values increased from 8.8 +/- 0.4 Gy to 10.5 +/- 0.5 Gy with AA-ORS
      treatment (P < 0.01), indicating an increased radiation tolerance of 1.7 Gy. We
      also found that AA-ORS treatment (1) increased Lgr5+, without altering Bmi1
      positive cells; (2) increased levels of proliferation markers (Ki-67, p-Erk, p
      Akt and PCNA); (3) decreased apoptosis markers, such as cleaved caspase-3 and Bcl
      2; and (4) increased expression and protein levels of NHE3 and SGLT1 in the brush
      border membrane. This study shows that AA-ORS increased villus height and
      improved electrolyte and nutrient absorption.

PMID- 27876793
TI  - PEP-19 modulates calcium binding to calmodulin by electrostatic steering.
AB  - PEP-19 is a small protein that increases the rates of Ca2+ binding to the C
      domain of calmodulin (CaM) by an unknown mechanism. Although an IQ motif promotes
      binding to CaM, an acidic sequence in PEP-19 is required to modulate Ca2+ binding
      and to sensitize HeLa cells to ATP-induced Ca2+ release. Here, we report the NMR
      solution structure of a complex between PEP-19 and the C-domain of apo CaM. The
      acidic sequence of PEP-19 associates between helices E and F of CaM via
      hydrophobic interactions. This allows the acidic side chains in PEP-19 to extend
      toward the solvent and form a negatively charged surface that resembles a
      catcher's mitt near Ca2+ binding loop III of CaM. The topology and gradients of
      negative electrostatic surface potential support a mechanism by which PEP-19
      increases the rate of Ca2+ binding to the C-domain of CaM by 'catching' and
      electrostatically steering Ca2+ to site III.

PMID- 27876795
TI  - Exact research on the theory of the blackbody thermal radiation.
AB  - After studying the normalized Planck equation in depth, a brand-new type of
      spectrum curves of blackbody thermal radiation is given. Two important parameters
      of the new type curves, namely relative width RWeta and symmetric factor RSFeta,
      are defined. The paper points out that the experimental verification of the
      parameters has three significant applications: (1) Giving a method to measure
      temperature by detecting the radiation wavelength. (2) Determining the blackbody
      grade. (3) The temperature obtained from the law of the blackbody thermal
      radiation can be used as a criterion.

PMID- 27876792
TI  - mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation
      to Cold.
AB  - In response to cold, brown adipose tissue (BAT) increases its metabolic rate and
      expands its mass to produce heat required for survival, a process known as BAT
      recruitment. The mechanistic target of rapamycin complex 1 (mTORC1) controls
      metabolism, cell growth and proliferation, but its role in regulating BAT
      recruitment in response to chronic cold stimulation is unknown. Here, we show
      that cold activates mTORC1 in BAT, an effect that depends on the sympathetic
      nervous system. Adipocyte-specific mTORC1 loss in mice completely blocks cold
      induced BAT expansion and severely impairs mitochondrial biogenesis. Accordingly,
      mTORC1 loss reduces oxygen consumption and causes a severe defect in BAT
      oxidative metabolism upon cold exposure. Using in vivo metabolic imaging,
      metabolomics and transcriptomics, we show that mTORC1 deletion impairs glucose
      and lipid oxidation, an effect linked to a defect in tricarboxylic acid (TCA)
      cycle activity. These analyses also reveal a severe defect in nucleotide
      synthesis in the absence of mTORC1. Overall, these findings demonstrate an
      essential role for mTORC1 in the regulation of BAT recruitment and metabolism in
      response to cold.

PMID- 27876794
TI  - VCAM1 acts in parallel with CD69 and is required for the initiation of
      oligodendrocyte myelination.
AB  - Oligodendrocytes differentiate to wrap their plasma membranes around axons,
      forming the myelin sheath. A neuronal cue is one of the regulator elements
      controlling this process. Here, we demonstrate that VCAM1, which plays a key role
      throughout the immune system, is also expressed in oligodendrocytes, where it
      regulates the initiation of myelination. VCAM1 knockout mice exhibit reduced
      myelin thickness. Decreased myelin thickness is also observed in mutant mice of
      alpha4 integrin, which is a neuronal VCAM1 ligand. Furthermore, CD69 is
      identified as one of the transcripts downregulated when VCAM1 is knocked down in
      oligodendrocytes. Knockdown of CD69 in mice indicates its role in myelination.
      Therefore, VCAM1 contributes not only to the initiation of myelination but also
      to its regulation through controlling the abundance of CD69, demonstrating that
      an intercellular molecule whose primary role is in the immune system can also
      play an unexpected role in the CNS.

PMID- 27876797
TI  - All-gas-phase synthesis of UiO-66 through modulated atomic layer deposition.
AB  - Thin films of stable metal-organic frameworks (MOFs) such as UiO-66 have enormous
      application potential, for instance in microelectronics. However, all-gas-phase
      deposition techniques are currently not available for such MOFs. We here report
      on thin-film deposition of the thermally and chemically stable UiO-66 in an all
      gas-phase process by the aid of atomic layer deposition (ALD). Sequential
      reactions of ZrCl4 and 1,4-benzenedicarboxylic acid produce amorphous organic
      inorganic hybrid films that are subsequently crystallized to the UiO-66 structure
      by treatment in acetic acid vapour. We also introduce a new approach to control
      the stoichiometry between metal clusters and organic linkers by modulation of the
      ALD growth with additional acetic acid pulses. An all-gas-phase synthesis
      technique for UiO-66 could enable implementations in microelectronics that are
      not compatible with solvothermal synthesis. Since this technique is ALD-based, it
      could also give enhanced thickness control and the possibility to coat irregular
      substrates with high aspect ratios.

PMID- 27876798
TI  - Proliferation of Listeria monocytogenes L-form cells by formation of internal and
      external vesicles.
AB  - L-forms are cell wall-deficient bacteria that divide through unusual mechanisms,
      involving dynamic perturbations of the cellular shape and generation of vesicles,
      independently of the cell-division protein FtsZ. Here we describe FtsZ
      independent mechanisms, involving internal and external vesicles, by which
      Listeria monocytogenes L-forms proliferate. Using micromanipulation of single
      cells and vesicles, we show that small vesicles are formed by invagination within
      larger intracellular vesicles, receive cytoplasmic content, and represent viable
      progeny. In addition, the L-forms can reproduce by pearling, that is, generation
      of extracellular vesicles that remain transiently linked to their mother cell via
      elastic membranous tubes. Using photobleaching and fluorescence recovery, we
      demonstrate cytoplasmic continuity and transfer through these membranous tubes.
      Our findings indicate that L-forms' polyploidy and extended interconnectivity
      through membranous tubes contribute to the generation of viable progeny
      independently of dedicated division machinery, and further support L-forms as
      models for studies of potential multiplication mechanisms of hypothetical
      primitive cells.

PMID- 27876796
TI  - Functional implications of orientation maps in primary visual cortex.
AB  - Stimulus orientation in the primary visual cortex of primates and carnivores is
      mapped as iso-orientation domains radiating from pinwheel centres, where
      orientation preferences of neighbouring cells change circularly. Whether this
      orientation map has a function is currently debated, because many mammals, such
      as rodents, do not have such maps. Here we show that two fundamental properties
      of visual cortical responses, contrast saturation and cross-orientation
      suppression, are stronger within cat iso-orientation domains than at pinwheel
      centres. These differences develop when excitation (not normalization) from
      neighbouring oriented neurons is applied to different cortical orientation
      domains and then balanced by inhibition from un-oriented neurons. The functions
      of the pinwheel mosaic emerge from these local intra-cortical computations:
      Narrower tuning, greater cross-orientation suppression and higher contrast gain
      of iso-orientation cells facilitate extraction of object contours from images,
      whereas broader tuning, greater linearity and less suppression of pinwheel cells
      generate selectivity for surface patterns and textures.

PMID- 27876800
TI  - Rapid laccolith intrusion driven by explosive volcanic eruption.
AB  - Magmatic intrusions and volcanic eruptions are intimately related phenomena.
      Shallow magma intrusion builds subsurface reservoirs that are drained by volcanic
      eruptions. Thus, the long-held view is that intrusions must precede and feed
      eruptions. Here we show that explosive eruptions can also cause magma intrusion.
      We provide an account of a rapidly emplaced laccolith during the 2011 rhyolite
      eruption of Cordon Caulle, Chile. Remote sensing indicates that an intrusion
      began after eruption onset and caused severe (>200 m) uplift over 1 month.
      Digital terrain models resolve a laccolith-shaped body ~0.8 km3. Deformation and
      conduit flow models indicate laccolith depths of only ~20-200 m and overpressures
      (~1-10 MPa) that likely stemmed from conduit blockage. Our results show that
      explosive eruptions may rapidly force significant quantities of magma in the
      crust to build laccoliths. These iconic intrusions can thus be interpreted as
      eruptive features that pose unique and previously unrecognized volcanic hazards.

PMID- 27876799
TI  - IRS4 induces mammary tumorigenesis and confers resistance to HER2-targeted
      therapy through constitutive PI3K/AKT-pathway hyperactivation.
AB  - In search of oncogenic drivers and mechanisms affecting therapy resistance in
      breast cancer, we identified Irs4, a poorly studied member of the insulin
      receptor substrate (IRS) family, as a mammary oncogene by insertional
      mutagenesis. Whereas normally silent in the postnatal mammary gland, IRS4 is
      found to be highly expressed in a subset of breast cancers. We show that Irs4
      expression in mammary epithelial cells induces constitutive PI3K/AKT pathway
      hyperactivation, insulin/IGF1-independent cell proliferation, anchorage
      independent growth and in vivo tumorigenesis. The constitutive PI3K/AKT pathway
      hyperactivation by IRS4 is unique to the IRS family and we identify the lack of a
      SHP2-binding domain in IRS4 as the molecular basis of this feature. Finally, we
      show that IRS4 and ERBB2/HER2 synergistically induce tumorigenesis and that IRS4
      expression confers resistance to HER2-targeted therapy. Taken together, our
      findings present the cellular and molecular mechanisms of IRS4-induced
      tumorigenesis and establish IRS4 as an oncogenic driver and biomarker for therapy
      resistance in breast cancer.

PMID- 27876801
TI  - PPFIA1 drives active alpha5beta1 integrin recycling and controls fibronectin
      fibrillogenesis and vascular morphogenesis.
AB  - Basolateral polymerization of cellular fibronectin (FN) into a meshwork drives
      endothelial cell (EC) polarity and vascular remodelling. However, mechanisms
      coordinating alpha5beta1 integrin-mediated extracellular FN endocytosis and
      exocytosis of newly synthesized FN remain elusive. Here we show that, on Rab21
      elicited internalization, FN-bound/active alpha5beta1 is recycled to the EC
      surface. We identify a pathway, comprising the regulators of post-Golgi carrier
      formation PI4KB and AP-1A, the small GTPase Rab11B, the surface tyrosine
      phosphatase receptor PTPRF and its adaptor PPFIA1, which we propose acts as a
      funnel combining FN secretion and recycling of active alpha5beta1 integrin from
      the trans-Golgi network (TGN) to the EC surface, thus allowing FN
      fibrillogenesis. In this framework, PPFIA1 interacts with active alpha5beta1
      integrin and localizes close to EC adhesions where post-Golgi carriers are
      targeted. We show that PPFIA1 is required for FN polymerization-dependent
      vascular morphogenesis, both in vitro and in the developing zebrafish embryo.

PMID- 27876802
TI  - Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn's
      disease.
AB  - Intestinal microbial dysbiosis is associated with Crohn's disease (CD). However,
      the mechanisms leading to the chronic mucosal inflammation that characterizes
      this disease remain unclear. In this report, we use systems-level approaches to
      study the interactions between the gut microbiota and host in new-onset
      paediatric patients to evaluate causality and mechanisms of disease. We report an
      altered host proteome in CD patients indicative of impaired mitochondrial
      functions. In particular, mitochondrial proteins implicated in H2S detoxification
      are downregulated, while the relative abundance of H2S microbial producers is
      increased. Network correlation analysis reveals that Atopobium parvulum controls
      the central hub of H2S producers. A. parvulum induces pancolitis in colitis
      susceptible interleukin-10-deficient mice and this phenotype requires the
      presence of the intestinal microbiota. Administrating the H2S scavenger bismuth
      mitigates A. parvulum-induced colitis in vivo. This study reveals that host
      microbiota interactions are disturbed in CD and thus provides mechanistic
      insights into CD pathogenesis.

PMID- 27876803
TI  - Association mapping for phenology and plant architecture in maize shows higher
      power for developmental traits compared with growth influenced traits.
AB  - Plant architecture, phenology and yield components of cultivated plants have
      repeatedly been shaped by selection to meet human needs and adaptation to
      different environments. Here we assessed the genetic architecture of 24
      correlated maize traits that interact during plant cycle. Overall, 336 lines were
      phenotyped in a network of 9 trials and genotyped with 50K single-nucleotide
      polymorphisms. Phenology was the main factor of differentiation between genetic
      groups. Then yield components distinguished dents from lower yielding genetic
      groups. However, most of trait variation occurred within group and we observed
      similar overall and within group correlations, suggesting a major effect of
      pleiotropy and/or linkage. We found 34 quantitative trait loci (QTLs) for
      individual traits and six for trait combinations corresponding to PCA
      coordinates. Among them, only five were pleiotropic. We found a cluster of QTLs
      in a 5 Mb region around Tb1 associated with tiller number, ear row number and the
      first PCA axis, the latter being positively correlated to flowering time and
      negatively correlated to yield. Kn1 and ZmNIP1 were candidate genes for
      tillering, ZCN8 for leaf number and Rubisco Activase 1 for kernel weight.
      Experimental repeatabilities, numbers of QTLs and proportion of explained
      variation were higher for traits related to plant development such as tillering,
      leaf number and flowering time, than for traits affected by growth such as yield
      components. This suggests a simpler genetic determinism with larger individual
      QTL effects for the first category.

PMID- 27876804
TI  - Inbreeding depression by environment interactions in a free-living mammal
      population.
AB  - Experimental studies often find that inbreeding depression is more severe in
      harsh environments, but the few studies of in situ wild populations available to
      date rarely find strong support for this effect. We investigated evidence for
      inbreeding depression by environment interactions in nine traits in the
      individually monitored Soay sheep population of St Kilda, using genomic
      inbreeding coefficients based on 37 037 single-nucleotide polymorphism loci, and
      population density as an axis of environmental variation. All traits showed
      variation with population density and all traits showed some evidence for
      depression because of either an individual's own inbreeding or maternal
      inbreeding. However, only six traits showed evidence for an interaction in the
      expected direction, and only two interactions were statistically significant. We
      identify three possible reasons why wild population studies may generally fail to
      find strong support for interactions between inbreeding depression and
      environmental variation compared with experimental studies. First, for species
      with biparental inbreeding only, the amount of observed inbreeding in natural
      populations is generally low compared with that used in experimental studies.
      Second, it is possible that experimental studies sometimes actually impose higher
      levels of stress than organisms experience in the wild. Third, some purging of
      the deleterious recessive alleles that underpin interaction effects may occur in
      the wild.

PMID- 27876805
TI  - Landscape genetics informs mesohabitat preference and conservation priorities for
      a surrogate indicator species in a highly fragmented river system.
AB  - Poor dispersal species represent conservative benchmarks for biodiversity
      management because they provide insights into ecological processes influenced by
      habitat fragmentation that are less evident in more dispersive organisms. Here we
      used the poorly dispersive and threatened river blackfish (Gadopsis marmoratus)
      as a surrogate indicator system for assessing the effects of fragmentation in
      highly modified river basins and for prioritizing basin-wide management
      strategies. We combined individual, population and landscape-based approaches to
      analyze genetic variation in samples spanning the distribution of the species in
      Australia's Murray-Darling Basin, one of the world's most degraded freshwater
      systems. Our results indicate that G. marmoratus displays the hallmark of severe
      habitat fragmentation with notably scattered, small and demographically isolated
      populations with very low genetic diversity-a pattern found not only between
      regions and catchments but also between streams within catchments. By using
      hierarchically nested population sampling and assessing relationships between
      genetic uniqueness and genetic diversity across populations, we developed a
      spatial management framework that includes the selection of populations in need
      of genetic rescue. Landscape genetics provided an environmental criterion to
      identify associations between landscape features and ecological processes. Our
      results further our understanding of the impact that habitat quality and quantity
      has on habitat specialists with similarly low dispersal. They should also have
      practical applications for prioritizing both large- and small-scale conservation
      management actions for organisms inhabiting highly fragmented ecosystems.

PMID- 27876806
TI  - A randomised controlled trial comparing a dietary antiplatelet, the water-soluble
      tomato extract Fruitflow, with 75 mg aspirin in healthy subjects.
AB  - BACKGROUND/OBJECTIVES: Increasing numbers of food ingredients are gaining
      acknowledgement, via regulated health claims, of benefits to human health. One
      such is a water-soluble tomato extract, Fruitflow (FF), a dietary antiplatelet.
      We examined relative platelet responses to FF and to 75 mg aspirin (ASA) in
      healthy subjects. SUBJECTS/METHODS: A total of 47 healthy subjects completed a
      double-blinded randomised controlled trial following a crossover design. Acute
      and 7-day treatments with 75 mg ASA were compared with control with and without
      concomitant FF, over a 5-h timecourse. Platelet aggregation response agonist,
      platelet thromboxane A2 release, plasma clotting times and time to form a primary
      haemostatic clot (PFA-100 closure time, TTC) were measured. RESULTS:
      Administration of all treatments lowered platelet function and thromboxane A2
      generation, and extended the TTC, relative to baseline (P<0.001) and to control
      (P<0.001). Plasma clotting times were not affected. A single 75 mg dose of ASA
      showed approximately equal efficacy to a dose of FF, whereas daily 75 mg ASA was
      approximately three times as effective after 7 days (P=0.002). Platelet responses
      were heterogenous with distinct weak and strong responder groups. Weak ASA
      responders retained a functional platelet response to collagen agonist and were
      responsive to FF. Concomitant FF and ASA did not lead to significant additive
      effects. CONCLUSIONS: The suppression of platelet function observed after
      consuming FF is approximately one-third that of daily 75 mg ASA. The reversible
      action of FF renders it less likely to overextend the time to form a primary
      haemostatic clot than ASA, an important safety consideration for primary
      prevention.

PMID- 27876807
TI  - Assessment of human energy exchange: historical overview.
AB  - Energy exchange is fundamental to life and is a cornerstone in the study of human
      physiology, metabolism and nutrition. A global effort is underway to further our
      understanding of human energy exchange and its components as a means of
      establishing the mechanistic underpinnings of the evolving obesity and chronic
      disease epidemics. The current report establishes a conceptual historical
      framework for examining the evolution of energy exchange concepts and measurement
      methods. We review developments taking place over more than 2000 years during
      which humans endeavored to establish the source of body heat, the 'fire of life'.
      Major conceptual and methodological advances over the past three centuries have
      incrementally advanced the field and created the energy exchange paradigm within
      which we now work. As in the past, innovative experimental ideas and measurement
      methods are now needed to answer important questions brought to light by the
      obesity and chronic disease epidemics. Nevertheless, older classical measurement
      methods based on calorimetry techniques still hold a strong position in the field
      as many diet and weight-related questions remain unanswered.

PMID- 27876808
TI  - Water intake and urinary hydration biomarkers in children.
AB  - BACKGROUND/OBJECTIVES: The aims of the study were as follows: (1) examine fluid
      intake and urinary hydration markers of children in Greece, (2) determine the
      calculated relative risk of hypohydration in children who did not meet the
      recommendations for daily water intake provided by the Institute of Medicine and
      the European Food Safety Authority compared with those who did and (3) analyze
      the efficacy of the recommendations as a method to achieve euhydration in
      children. SUBJECTS/METHODS: One hundred and fifty Greek boys and girls (age 9-13)
      recorded their fluid intake for 2 consecutive days. A 24-h urine collection was
      obtained during the second day. Fluid intake records were analyzed for total
      water intake from fluids (TWI-F), and urine samples were analyzed for osmolality,
      color, specific gravity and volume. Urine osmolality ?800 mmol/kg H2O was defined
      as hypohydration. RESULTS: Water intake from fluids was 1729 (1555-1905) and 1550
      (1406-1686) ml/d for boys and girls, respectively. Prevalence of hypohydration
      was 33% (44% of boys, 23% of girls). Children who failed to meet TWI-F
      recommendations demonstrated a risk of hypohydration that was 1.99-2.12 times
      higher than those who met recommendations (P?0.01). Boys between 9 and 13 years
      displayed urine osmolality of 777 (725-830) mmol/kg, and urine specific gravity
      of 1.021 (1.019-1.022), which was higher than those in girls between 9-13 years
      (P?0.015), and >27% were classified as hypohydrated despite meeting water intake
      recommendations. CONCLUSIONS: Failure to meet TWI-F guidelines increased
      calculated relative risk of hypohydration in children. Boys between 9 and 13
      years are at greater hazard regardless of meeting guidelines and may require
      greater water intake to avoid elevated urine concentration and ensure adequate
      hydration.

PMID- 27876809
TI  - Cold-induced thermogenesis in humans.
AB  - A basic property of endothermic thermoregulation is the ability to generate heat
      by increasing metabolism in response to cold ambient temperatures to maintain a
      stable core body temperature. This process, known as cold-induced thermogenesis
      (CIT), has been measured in humans as early as 1780 by Antoine Lavoisier, but has
      found renewed interest because of the recent 'rediscovery' of thermogenic, cold
      activated brown adipose tissue (BAT) in adult humans. In this review, we
      summarize some of the key findings of the work involving CIT over the past two
      centuries and highlight some of the seminal studies focused on this topic. There
      has been a substantial range of variability in the reported CIT in these studies,
      from 0 to 280% above basal metabolism. We identify and discuss several potential
      sources of this variability, including both methodological (measurement device,
      cold exposure temperature and duration) and biological (age and body composition
      of subject population) discrepancies. These factors should be considered when
      measuring CIT going forward to better assess whether BAT or other thermogenic
      organs are viable targets to combat chronic positive energy balance based on
      their relative capacities to elevate human metabolism.

PMID- 27876810
TI  - Outcomes of exclusive enteral nutrition in paediatric Crohn's disease.
AB  - BACKGROUND/OBJECTIVES: Exclusive enteral nutrition (EEN) is a safe and effective
      treatment modality for inducing remission in paediatric Crohn's disease (CD). The
      primary aim of this study was to compare the outcomes of EEN to corticosteroid
      (CS) therapy in newly diagnosed, treatment-naive patients with CD. A secondary
      aim was to describe the outcomes of EEN in a national cohort of paediatric CD
      patients over a 10-year period. SUBJECTS/METHODS: A retrospective chart review
      was conducted at the Irish national referral centre for paediatric CD. A case
      matched analysis was conducted on two cohorts matched for age, gender, disease
      location, disease behaviour and disease activity, who received CS or EEN as their
      initial treatment. Subsequently, cohort analysis was conducted on all patients
      who undertook a course of EEN therapy between 2004 and 2013. RESULTS: The case
      matched analysis found higher remission rates after treatment with EEN (24/28,
      86%) compared with those with CS (15/28, 54%; P=0.02). Dietetic contacts were
      found to be pivotal to the success of treatment and the attainment of remission.
      In total, 59 patients completed EEN at some time-point in their disease course
      and were included in the cohort analysis. Sixty-nine per cent of this cohort
      entered clinical remission (41/59). EEN was found to be most effective when used
      as an initial treatment (P=0.004) and less effective in patients aged under 10
      years (P=0.04). CONCLUSIONS: EEN should be strongly considered as a favourable
      primary treatment over CS, especially in those diagnosed over the age of 10
      years.

PMID- 27876812
TI  - Corrigendum: Flux of signalling endosomes undergoing axonal retrograde transport
      is encoded by presynaptic activity and TrkB.

PMID- 27876811
TI  - Unlocking sperm chromatin at fertilization requires a dedicated egg thioredoxin
      in Drosophila.
AB  - In most animals, the extreme compaction of sperm DNA is achieved after the
      massive replacement of histones with sperm nuclear basic proteins (SNBPs), such
      as protamines. In some species, the ultracompact sperm chromatin is stabilized by
      a network of disulfide bonds connecting cysteine residues present in SNBPs.
      Studies in mammals have established that the reduction of these disulfide
      crosslinks at fertilization is required for sperm nuclear decondensation and the
      formation of the male pronucleus. Here, we show that the Drosophila maternal
      thioredoxin Deadhead (DHD) is specifically required to unlock sperm chromatin at
      fertilization. In dhd mutant eggs, the sperm nucleus fails to decondense and the
      replacement of SNBPs with maternally-provided histones is severely delayed, thus
      preventing the participation of paternal chromosomes in embryo development. We
      demonstrate that DHD localizes to the sperm nucleus to reduce its disulfide
      targets and is then rapidly degraded after fertilization.

PMID- 27876813
TI  - Oncogenic transformation of human lung bronchial epithelial cells induced by
      arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism.
AB  - Arsenic is a well-documented human carcinogen. The present study explored the
      role of the onco-miR, miR-21 and its target protein, programmed cell death 4
      (PDCD4) in arsenic induced malignant cell transformation and tumorigenesis. Our
      results showed that treatment of human bronchial epithelial (BEAS-2B) cells with
      arsenic induces ROS through p47phox, one of the NOX subunits that is the key
      source of arsenic-induced ROS. Arsenic exposure induced an upregulation of miR-21
      expression associated with inhibition of PDCD4, and caused malignant cell
      transformation and tumorigenesis of BEAS-2B cells. Indispensably, STAT3
      transcriptional activation by IL-6 is crucial for the arsenic induced miR-21
      increase. Upregulated miR-21 levels and suppressed PDCD4 expression was also
      observed in xenograft tumors generated with chronic arsenic exposed BEAS-2B
      cells. Stable shut down of miR-21, p47phox or STAT3 and overexpression of PDCD4
      or catalase in BEAS-2B cells markedly inhibited the arsenic induced malignant
      transformation and tumorigenesis. Similarly, silencing of miR-21 or STAT3 and
      forced expression of PDCD4 in arsenic transformed cells (AsT) also inhibited cell
      proliferation and tumorigenesis. Furthermore, arsenic suppressed the downstream
      protein E-cadherin expression and induced beta-catenin/TCF-dependent
      transcription of uPAR and c-Myc. These results indicate that the ROS-STAT3-miR-21
      PDCD4 signaling axis plays an important role in arsenic -induced carcinogenesis.

PMID- 27876814
TI  - A genome-wide investigation into parent-of-origin effects in autism spectrum
      disorder identifies previously associated genes including SHANK3.
AB  - Autism spectrum disorder (ASD) is known to be a heritable neurodevelopmental
      disorder affecting more than 1% of the population but in the majority of ASD
      cases, the genetic cause has not been identified. Parent-of-origin effects have
      been highlighted as an important mechanism in the pathology of neurodevelopmental
      disorders such as Prader-Willi and Angelman syndrome, with individuals with these
      syndromes often exhibiting ASD symptoms. Consequently, systematic investigation
      of these effects in ASD is clearly an important line of investigation in
      elucidating the underlying genetic mechanisms. Using estimation of maternal,
      imprinting and interaction effects using multinomial modelling (EMIM), we
      simultaneously investigated imprinting, maternal genetic effects and associations
      in the Autism Genome Project and Simons Simplex Consortium genome-wide
      association data sets. To avoid using the overly stringent genome-wide
      association study significance level, we used a Bayesian threshold that takes
      into account the sample size, allele frequency and any available prior knowledge.
      Between the two data sets, we identified a total of 18 imprinting effects and 68
      maternal genetic effects that met this Bayesian threshold criteria, but none met
      the threshold in both data sets. We identified imprinting and maternal genetic
      effects for regions that have previously shown evidence for parent-of-origin
      effects in ASD. Together with these findings, we have identified maternal genetic
      effects not previously identified in ASD at a locus in SHANK3 on chromosome 22
      and a locus in WBSCR17 on chromosome 7 (associated with Williams syndrome). Both
      genes have previously been associated with ASD.

PMID- 27876816
TI  - Reply to Kranendonk et al.

PMID- 27876815
TI  - Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in
      autosomal dominant familial Meniere's disease.
AB  - Autosomal dominant (AD) familial Meniere's disease (FMD) is a rare disorder
      involving the inner ear defined by sensorineural hearing loss, tinnitus and
      episodic vertigo. Here, we have identified two novel and rare heterozygous
      variants in the SEMA3D and DPT genes segregating with the complete phenotype that
      have variable expressivity in two pedigrees with AD-FMD. A detailed
      characterization of the phenotype within each family illustrates the clinical
      heterogeneity in the onset and progression of the disease. We also showed the
      expression of both genes in the human cochlea and performed in silico analyses of
      these variants. Three-dimensional protein modelling showed changes in the
      structure of the protein indicating potential physical interactions. These
      results confirm a genetic heterogeneity in FMD with incomplete penetrance and
      variable expressivity.

PMID- 27876819
TI  - The Dutch legal approach regarding health care decisions involving minors in the
      NGS days.

PMID- 27876818
TI  - Identification and characterization of 5' CCG interruptions in complex DMPK
      expanded alleles.
AB  - Myotonic dystrophy type 1 is a multisystemic autosomal dominant disorder caused
      by the expansion of (CTG) n triplets in the 3'UTR of the DMPK gene, on chromosome
      19q13.3. In the last years, few DM1 patients with different patterns of CCG/CTC
      interruptions at the 3' end of the DMPK expanded tract have been described.
      However, the role of these interruptions in DM1 pathogenesis is still unclear. To
      study the frequency, stability and the structure of DMPK variant expanded alleles
      in the Italian population, we have re-evaluated 254 Italian DM1 patients using
      triplet-primed PCR (TP-PCR), at both the 3' and 5' ends of the CTG expansion. In
      addition, three DM1 families were also investigated in order to analyze the
      intergenerational stability of the interrupted DMPK alleles. Fourteen DM1
      patients showed a TP-PCR electrophoretic profile indicating CCG/CTC interruptions
      within the CTG expansion. Interestingly, interruptions have been detected and,
      for the first time, sequenced at the 5' end of the CTG array. Analysis of five
      intergenerational transmissions revealed a substantial intrafamilial stability of
      the DM1 mutation among relatives. Our results support the hypothesis that CCG/CTC
      interruptions within the DMPK expanded alleles have a stabilizing effect on the
      mutational dynamics and can modulate the severity of symptoms in DM1 patients.

PMID- 27876817
TI  - A framework for the detection of de novo mutations in family-based sequencing
      data.
AB  - Germline mutation detection from human DNA sequence data is challenging due to
      the rarity of such events relative to the intrinsic error rates of sequencing
      technologies and the uneven coverage across the genome. We developed
      PhaseByTransmission (PBT) to identify de novo single nucleotide variants and
      short insertions and deletions (indels) from sequence data collected in parent
      offspring trios. We compute the joint probability of the data given the genotype
      likelihoods in the individual family members, the known familial relationships
      and a prior probability for the mutation rate. Candidate de novo mutations (DNMs)
      are reported along with their posterior probability, providing a systematic way
      to prioritize them for validation. Our tool is integrated in the Genome Analysis
      Toolkit and can be used together with the ReadBackedPhasing module to infer the
      parental origin of DNMs based on phase-informative reads. Using simulated data,
      we show that PBT outperforms existing tools, especially in low coverage data and
      on the X chromosome. We further show that PBT displays high validation rates on
      empirical parent-offspring sequencing data for whole-exome data from 104 trios
      and X-chromosome data from 249 parent-offspring families. Finally, we demonstrate
      an association between father's age at conception and the number of DNMs in
      female offspring's X chromosome, consistent with previous literature reports.

PMID- 27876820
TI  - A method to customize population-specific arrays for genome-wide association
      testing.
AB  - As an example of optimizing population-specific genotyping assays using a whole
      genome sequence reference set, we detail the approach that followed to design the
      Axiom-NL array which is characterized by an improved imputation backbone based on
      the Genome of the Netherlands (GoNL) reference sequence and, compared with
      earlier arrays, a more comprehensive inclusion of SNPs on chromosomes X, Y, and
      the mitochondria. Common variants on the array were selected to be compatible
      with the Illumina Psych Array and the Affymetrix UK Biobank Axiom array. About
      3.5% of the array (23 977 markers) represents SNPs from the GWAS catalog,
      including SNPs at FTO, APOE, Ion-channels, killer-cell immunoglobulin-like
      receptors, and HLA. Around 26 000 markers associated with common psychiatric
      disorders are included, as well as 6705 markers suggested to be associated with
      fertility and twinning. The platform can thus be used for risk profiling,
      detection of new variants, as well as ancestry determination. Results of coverage
      tests in 249 unrelated subjects with GoNL-based sequence data show that after
      imputation with 1000G as a reference, the median concordance between original and
      imputed genotypes is above 98%. The median imputation quality R2 for MAF
      thresholds of 0.001, 0.01, 0.05, and >0.05 are 0.05, 0.28, 0.80, 0.99,
      respectively, for the 1000G imputed SNPs, with a similar quality for the
      autosomes and X chromosome, showing a good genome-wide coverage for association
      studies after imputation.

PMID- 27876821
TI  - Logic models to predict continuous outputs based on binary inputs with an
      application to personalized cancer therapy.
AB  - Mining large datasets using machine learning approaches often leads to models
      that are hard to interpret and not amenable to the generation of hypotheses that
      can be experimentally tested. We present 'Logic Optimization for Binary Input to
      Continuous Output' (LOBICO), a computational approach that infers small and
      easily interpretable logic models of binary input features that explain a
      continuous output variable. Applying LOBICO to a large cancer cell line panel, we
      find that logic combinations of multiple mutations are more predictive of drug
      response than single gene predictors. Importantly, we show that the use of the
      continuous information leads to robust and more accurate logic models. LOBICO
      implements the ability to uncover logic models around predefined operating points
      in terms of sensitivity and specificity. As such, it represents an important step
      towards practical application of interpretable logic models.

PMID- 27876823
TI  - Alignment-free Transcriptomic and Metatranscriptomic Comparison Using Sequencing
      Signatures with Variable Length Markov Chains.
AB  - The comparison between microbial sequencing data is critical to understand the
      dynamics of microbial communities. The alignment-based tools analyzing
      metagenomic datasets require reference sequences and read alignments. The
      available alignment-free dissimilarity approaches model the background sequences
      with Fixed Order Markov Chain (FOMC) yielding promising results for the
      comparison of microbial communities. However, in FOMC, the number of parameters
      grows exponentially with the increase of the order of Markov Chain (MC). Under a
      fixed high order of MC, the parameters might not be accurately estimated owing to
      the limitation of sequencing depth. In our study, we investigate an alternative
      to FOMC to model background sequences with the data-driven Variable Length Markov
      Chain (VLMC) in metatranscriptomic data. The VLMC originally designed for long
      sequences was extended to apply to high-throughput sequencing reads and the
      strategies to estimate the corresponding parameters were developed. The flexible
      number of parameters in VLMC avoids estimating the vast number of parameters of
      high-order MC under limited sequencing depth. Different from the manual selection
      in FOMC, VLMC determines the MC order adaptively. Several beta diversity measures
      based on VLMC were applied to compare the bacterial RNA-Seq and
      metatranscriptomic datasets. Experiments show that VLMC outperforms FOMC to model
      the background sequences in transcriptomic and metatranscriptomic samples. A
      software pipeline is available at https://d2vlmc.codeplex.com.

PMID- 27876824
TI  - Non-stimulated adrenal venous sampling using Dyna computed tomography in patients
      with primary aldosteronism.
AB  - In this retrospective study, we aimed to examine the effect of applying Dyna
      computed tomography (CT) on the success rate of adrenal venous sampling (AVS)
      without adrenocorticotropic hormone stimulation. A total of 100 consecutive
      patients with primary aldosteronism who underwent AVS between May 2012 and July
      2015 were enrolled. In all the cases, Dyna CT was used in AVS to validate
      catheter position in the right adrenal vein. A selectivity index (cortisoladrenal
      vein /cortisolinferior vena cava) of >=2.0 of both adrenal veins were required
      for successful AVS. Dyna CT indicated misplaced catheters in 16 patients; of
      these patients, 75% (12/16) eventually had successful right AVS after catheter
      repositioning. The success rate of initial sampling at the right adrenal vein was
      76% (76/100), which increased to 88% (88/100) after Dyna CT was applied (p <
      0.001). The most common inadvertently catheterised vessels detected using Dyna CT
      were the accessory hepatic veins (56.3%, 9/16), followed by the renal capsular
      veins (37.5%, 6/16). The overall success rate of non-stimulated AVS using Dyna CT
      was 87% (87/100). Thus, the application of Dyna CT further increased the success
      rate of non-stimulated AVS.

PMID- 27876825
TI  - Toward a new paradigm of DNA writing using a massively parallel sequencing
      platform and degenerate oligonucleotide.
AB  - All synthetic DNA materials require prior programming of the building blocks of
      the oligonucleotide sequences. The development of a programmable microarray
      platform provides cost-effective and time-efficient solutions in the field of
      data storage using DNA. However, the scalability of the synthesis is not on par
      with the accelerating sequencing capacity. Here, we report on a new paradigm of
      generating genetic material (writing) using a degenerate oligonucleotide and
      optomechanical retrieval method that leverages sequencing (reading) throughput to
      generate the desired number of oligonucleotides. As a proof of concept, we
      demonstrate the feasibility of our concept in digital information storage in DNA.
      In simulation, the ability to store data is expected to exponentially increase
      with increase in degenerate space. The present study highlights the major
      framework change in conventional DNA writing paradigm as a sequencer itself can
      become a potential source of making genetic materials.

PMID- 27876827
TI  - Soil organic carbon accumulation during post-agricultural succession in a karst
      area, southwest China.
AB  - This study was aimed to investigate the direction and magnitude of soil organic
      carbon (SOC) dynamics and the underlying mechanisms following agricultural
      abandonment in a subtropical karst area, southwest China. Two post-agriculture
      succession sequences including grassland (~10 years), shrubland (~29 years),
      secondary forest (~59 years) and primary forest with cropland as reference were
      selected. SOC and other soil physicochemical variables in the soil depth of 0-15
      cm (representing the average soil depth of the slope in the studied area) were
      measured. SOC content in the grassland was not significantly elevated relative to
      the cropland (42.0 +/- 7.3 Mg C ha-1). SOC content in the shrubland reached the
      level of the primary forest. On average, SOC content for the forest was 92.6 +/-
      4.2 Mg C ha-1, representing an increase of 120.4 +/- 10.0% or 50.6 +/- 4.2 Mg ha
      1 relative to the cropland. Following agricultural abandonment, SOC recovered to
      the primary forest level in about 40 years with a rate of 1.38 Mg C ha-1 yr-1.
      Exchangeable Ca and Mg were found to be the strongest predictors of SOC dynamics.
      Our results suggest that SOC content may recover rapidly following agricultural
      abandonment in the karst region of southwest China.

PMID- 27876826
TI  - BGRMI: A method for inferring gene regulatory networks from time-course gene
      expression data and its application in breast cancer research.
AB  - Reconstructing gene regulatory networks (GRNs) from gene expression data is a
      challenging problem. Existing GRN reconstruction algorithms can be broadly
      divided into model-free and model-based methods. Typically, model-free methods
      have high accuracy but are computation intensive whereas model-based methods are
      fast but less accurate. We propose Bayesian Gene Regulation Model Inference
      (BGRMI), a model-based method for inferring GRNs from time-course gene expression
      data. BGRMI uses a Bayesian framework to calculate the probability of different
      models of GRNs and a heuristic search strategy to scan the model space
      efficiently. Using benchmark datasets, we show that BGRMI has higher/comparable
      accuracy at a fraction of the computational cost of competing algorithms.
      Additionally, it can incorporate prior knowledge of potential gene regulation
      mechanisms and TF hetero-dimerization processes in the GRN reconstruction
      process. We incorporated existing ChIP-seq data and known protein interactions
      between TFs in BGRMI as sources of prior knowledge to reconstruct transcription
      regulatory networks of proliferating and differentiating breast cancer (BC) cells
      from time-course gene expression data. The reconstructed networks revealed key
      driver genes of proliferation and differentiation in BC cells. Some of these
      genes were not previously studied in the context of BC, but may have clinical
      relevance in BC treatment.

PMID- 27876828
TI  - Common variants in the PARL and PINK1 genes increase the risk to leprosy in Han
      Chinese from South China.
AB  - Leprosy is a chronic infectious and neurological disease caused by Mycobacterium
      leprae, an unculturable pathogen with massive genomic decay and dependence on
      host metabolism. We hypothesized that mitochondrial genes PARL and PINK1 would
      confer risk to leprosy. Thirteen tag SNPs of PARL and PINK1 were analyzed in 3620
      individuals with or without leprosy from China. We also sequenced the entire
      exons of PARL, PINK1 and PARK2 in 80 patients with a family history of leprosy by
      using the next generation sequencing technology (NGS). We found that PARL SNP
      rs12631031 conferred a risk to leprosy (Padjusted = 0.019) and multibacillary
      leprosy (MB, Padjusted = 0.020) at the allelic level. rs12631031 and rs7653061 in
      PARL were associated with leprosy and MB (dominant model, Padjusted < 0.05) at
      the genotypic level. PINK1 SNP rs4704 was associated with leprosy at the
      genotypic level (Padjusted = 0.004). We confirmed that common variants in PARL
      and PINK1 were associated with leprosy in patients underwent NGS. Furthermore,
      PARL and PINK1 could physically interact with each other and were involved in the
      highly connected network formed by reported leprosy susceptibility genes.
      Together, our results showed that PARL and PINK1 genetic variants are associated
      with leprosy.

PMID- 27876829
TI  - Integrated microRNA and messenger RNA analysis in aortic stenosis.
AB  - Aortic valve stenosis (AS) is a major cause of morbidity and mortality, with no
      effective medical therapies. Investigation into the underlying biology of AS in
      humans is limited by difficulties in obtaining healthy valvular tissue for use as
      a control group. However, micro-ribonucleic acids (miRNAs) are stable in post
      mortem tissue. We compared valve specimens from patients undergoing aortic valve
      replacement for AS to non-diseased cadaveric valves. We found 106 differentially
      expressed miRNAs (p < 0.05, adjusted for multiple comparisons) on microarray
      analysis, with highly correlated expression among up- and down-regulated miRNAs.
      Integrated miRNA/gene expression analysis validated the microarray results as a
      whole, while quantitative polymerase chain reaction confirmed downregulation of
      miR-122-5p, miR-625-5p, miR-30e-5p and upregulation of miR-21-5p and miR-221-3p.
      Pathway analysis of the integrated miRNA/mRNA network identified pathways
      predominantly involved in extracellular matrix function. A number of currently
      available therapies target products of upregulated genes in the integrated
      miRNA/mRNA network, with these genes being predominantly more peripheral members
      of the network. The identification of a group of tissue miRNA associated with AS
      may contribute to the development of new therapeutic approaches to AS. This study
      highlights the importance of systems biology-based approaches to complex
      diseases.

PMID- 27876830
TI  - Manipulation of Optical Transmittance by Ordered-Oxygen-Vacancy in Epitaxial
      LaBaCo2O5.5+delta Thin Films.
AB  - Giant optical transmittance changes of over 300% in wide wavelength range from
      500 nm to 2500 nm were observed in LaBaCo2O5.5+delta thin films annealed in air
      and ethanol ambient, respectively. The reduction process induces high density of
      ordered oxygen vacancies and the formation of LaBaCo2O5.5 (delta = 0) structure
      evidenced by aberration-corrected transmission electron microscopy. Moreover, the
      first-principles calculations reveal the origin and mechanism of optical
      transmittance enhancement in LaBaCo2O5.5 (delta = 0), which exhibits quite
      different energy band structure compared to that of LaBaCo2O6 (delta = 0.5). The
      discrepancy of energy band structure was thought to be the direct reason for the
      enhancement of optical transmission in reducing ambient. Hence, LaBaCo2O5.5+delta
      thin films show great prospect for applications on optical gas sensors in
      reducing/oxidizing atmosphere.

PMID- 27876831
TI  - Persistent northward North Atlantic tropical cyclone track migration over the
      past five centuries.
AB  - Accurately predicting future tropical cyclone risk requires understanding the
      fundamental controls on tropical cyclone dynamics. Here we present an annually
      resolved 450-year reconstruction of western Caribbean tropical cyclone activity
      developed using a new coupled carbon and oxygen isotope ratio technique in an
      exceptionally well-dated stalagmite from Belize. Western Caribbean tropical
      cyclone activity peaked at 1650 A.D., coincident with maximum Little Ice Age
      cooling, and decreased gradually until the end of the record in 1983. Considered
      with other reconstructions, the new record suggests that the mean track of Cape
      Verde tropical cyclones shifted gradually north-eastward from the western
      Caribbean toward the North American east coast over the last 450 years. Since
      ~1870 A.D., these shifts were largely driven by anthropogenic greenhouse gas and
      sulphate aerosol emissions. Our results strongly suggest that future emission
      scenarios will result in more frequent tropical cyclone impacts on the financial
      and population centres of the northeastern United States.

PMID- 27876833
TI  - Zeta potential in oil-water-carbonate systems and its impact on oil recovery
      during controlled salinity water-flooding.
AB  - Laboratory experiments and field trials have shown that oil recovery from
      carbonate reservoirs can be increased by modifying the brine composition injected
      during recovery in a process termed controlled salinity water-flooding (CSW).
      However, CSW remains poorly understood and there is no method to predict the
      optimum CSW composition. This work demonstrates for the first time that improved
      oil recovery (IOR) during CSW is strongly correlated to changes in zeta potential
      at both the mineral-water and oil-water interfaces. We report experiments in
      which IOR during CSW occurs only when the change in brine composition induces a
      repulsive electrostatic force between the oil-brine and mineral-brine interfaces.
      The polarity of the zeta potential at both interfaces must be determined when
      designing the optimum CSW composition. A new experimental method is presented
      that allows this. Results also show for the first time that the zeta potential at
      the oil-water interface may be positive at conditions relevant to carbonate
      reservoirs. A key challenge for any model of CSW is to explain why IOR is not
      always observed. Here we suggest that failures using the conventional (dilution)
      approach to CSW may have been caused by a positively charged oil-water interface
      that had not been identified.

PMID- 27876832
TI  - Knockout of Zebrafish Ovarian Aromatase Gene (cyp19a1a) by TALEN and CRISPR/Cas9
      Leads to All-male Offspring Due to Failed Ovarian Differentiation.
AB  - Sexual or gonadal differentiation is a complex event and its mechanism remains
      elusive in teleosts. Despite its complexity and plasticity, the process of
      ovarian differentiation is believed to involve gonadal aromatase (cyp19a1a) in
      nearly all species studied. However, most data concerning the role of aromatase
      have come from gene expression analysis or studies involving pharmacological
      approaches. There has been a lack of genetic evidence for the importance of
      aromatase in gonadal differentiation, especially the timing when the enzyme
      starts to exert its effect. This is due to the lack of appropriate loss-of
      function approaches in fish models for studying gene functions. This situation
      has changed recently with the development of genome editing technologies, namely
      TALEN and CRISPR/Cas9. Using both TALEN and CRISPR/Cas9, we successfully
      established three mutant zebrafish lines lacking the ovarian aromatase. As
      expected, all mutant fish were males, supporting the view that aromatase plays a
      critical role in directing ovarian differentiation and development. Further
      analysis showed that the ovarian aromatase did not seem to affect the formation
      of so-called juvenile ovary and oocyte-like germ cells; however, it was essential
      for further differentiation of the juvenile ovary into the true ovary.

PMID- 27876834
TI  - The measurement of lung volumes using body plethysmography and helium dilution
      methods in COPD patients: a correlation and diagnosis analysis.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic airway disease
      characterized by persistent airflow limitation. Moreover, lung hyperinflation
      evaluated by lung volumes is also the key pathophysiologic process during COPD
      progression. Nevertheless, there is still no preferred method to evaluate lung
      volumes. For this study, we recruited 170 patients with stable COPD to assess
      lung volumes stratified by airflow limitation severity. Lung volumes including
      residual volume (RV) and total lung capacity (TLC) were determined by both body
      plethysmography and helium dilution methods. The discrepancies between these two
      methods were recorded as DeltaRV%pred, DeltaTLC%pred, and DeltaRV/TLC. We found
      that DeltaRV%pred, DeltaTLC%pred, and DeltaRV/TLC increased significantly with
      the severity of COPD. The differences of lung capacity between these two methods
      were negatively correlated with FEV1%pred, and diffusing capacity for carbon
      monoxide (DLCO%pred). Moreover, the receiver operating characteristic (ROC) for
      DeltaTLC%pred to distinguish severe COPD from non-severe COPD had an area under
      curve (AUC) of 0.886. The differences of lung volume parameters measured by body
      plethysmography and helium dilution methods were associated with airflow
      limitation and can effectively differentiate COPD severity, which may be a
      supportive method to assess the lung function of stable COPD patients.

PMID- 27876835
TI  - Folic acid supplementation improves cognitive function by reducing the levels of
      peripheral inflammatory cytokines in elderly Chinese subjects with MCI.
AB  - This study aimed to evaluate whether folic acid supplementation would improve
      cognitive performance by reducing serum inflammatory cytokine concentrations.
      This RCT was performed in Tianjin, China. Participants with mild cognitive
      impairment (MCI) were randomly assigned to the folic acid (400 MUg/day) or
      conventional treatment groups. Neuropsychological tests were administered, and
      folate, homocysteine, vitamin B12, IL-6, TNF-alpha, Abeta-42, and Abeta-40 were
      measured at baseline and at 6- and 12-month time points.152 participants (folic
      acid: 77, conventional: 75) completed the trial. Significant improvements in
      folate (etap2 = 0.703, P = 0.011), homocysteine (etap2 = 0.644, P = 0.009), Abeta
      42 (etap2 = 0.687, P = 0.013), peripheral IL-6 (etap2 = 0.477, P = 0.025), TNF
      alpha (etap2 = 0.709, P = 0.009) levels were observed in folic acid group
      compared with conventional group. Folic acid supplementation improved the Full
      Scale Intelligence Quotient (P = 0.028; effect size d = 0.153), Information (P =
      0.031; d = 0.157) and Digit Span (P = 0.009; d = 0.172) scores at 12 months
      compared with conventional treatment. Based on these findings, daily oral
      administration of a 400-MUg folic acid supplement to MCI subjects for 12 months
      can significantly improve cognitive performance and reduce peripheral
      inflammatory cytokine levels.

PMID- 27876838
TI  - A new grading system for plant-available potassium using exhaustive cropping
      techniques combined with chemical analyses of soils.
AB  - A new grading system for plant-available potassium (K) in soils based on K
      release rate from soils and plant growth indices was established. In the study,
      fourteen different agricultural soils from the southern subtropical to the
      northern temperate zones in China were analyzed by both chemical extraction
      methods and exhaustive cropping techniques. Based on the change trends in plant
      growth indices, relative biomass yields of 70% and 50%, K-deficient coefficients
      of 35 and 22 under conventional exhaustive experiments, and tissue K
      concentrations of 40 g kg-1 and 15 g kg-1 under intensive exhaustive experiments
      were obtained as critical values that represent different change trends. In
      addition, the extraction method using 0.2 mol L-1 sodium tetraphenylboron (NaTPB)
      suggested soil K release rates of 12 mg kg-1 min-1 and 0.4 mg kg-1 min-1 as
      turning points that illustrated three different release trends. Thus, plant
      available K in soils was classified into three categories: high available K,
      medium available K and low available K, and grading criteria and measurement
      methods were also proposed. This work has increased our understanding of soil K
      bioavailability and has direct application in terms of routine assessment of
      agriculture soils.

PMID- 27876836
TI  - NF-kappaBeta-inducing kinase regulates stem cell phenotype in breast cancer.
AB  - Breast cancer stem cells (BCSCs) overexpress components of the Nuclear factor
      kappa B (NF-kappaB) signaling cascade and consequently display high NF-kappaB
      activity levels. Breast cancer cell lines with high proportion of CSCs exhibit
      high NF-kappaB-inducing kinase (NIK) expression. The role of NIK in the phenotype
      of cancer stem cell regulation is poorly understood. Expression of NIK was
      analyzed by quantitative RT-PCR in BCSCs. NIK levels were manipulated through
      transfection of specific shRNAs or an expression vector. The effect of NIK in the
      cancer stem cell properties was assessed by mammosphere formation, mice
      xenografts and stem markers expression. BCSCs expressed higher levels of NIK and
      its inhibition through small hairpin (shRNA), reduced the expression of CSC
      markers and impaired clonogenicity and tumorigenesis. Genome-wide expression
      analyses suggested that NIK acts on ERK1/2 pathway to exert its activity. In
      addition, forced expression of NIK increased the BCSC population and enhanced
      breast cancer cell tumorigenicity. The in vivo relevance of these results is
      further supported by a tissue microarray of breast cancer samples in which we
      observed correlated expression of Aldehyde dehydrogenase (ALDH) and NIK protein.
      Our results support the essential involvement of NIK in BCSC phenotypic
      regulation via ERK1/2 and NF-kappaB.

PMID- 27876837
TI  - The Mediterranean Plastic Soup: synthetic polymers in Mediterranean surface
      waters.
AB  - The Mediterranean Sea has been recently proposed as one of the most impacted
      regions of the world with regards to microplastics, however the polymeric
      composition of these floating particles is still largely unknown. Here we present
      the results of a large-scale survey of neustonic micro- and meso-plastics
      floating in Mediterranean waters, providing the first extensive characterization
      of their chemical identity as well as detailed information on their abundance and
      geographical distribution. All particles >700 MUm collected in our samples were
      identified through FT-IR analysis (n = 4050 particles), shedding for the first
      time light on the polymeric diversity of this emerging pollutant. Sixteen
      different classes of synthetic materials were identified. Low-density polymers
      such as polyethylene and polypropylene were the most abundant compounds, followed
      by polyamides, plastic-based paints, polyvinyl chloride, polystyrene and
      polyvinyl alcohol. Less frequent polymers included polyethylene terephthalate,
      polyisoprene, poly(vinyl stearate), ethylene-vinyl acetate, polyepoxide, paraffin
      wax and polycaprolactone, a biodegradable polyester reported for the first time
      floating in off-shore waters. Geographical differences in sample composition were
      also observed, demonstrating sub-basin scale heterogeneity in plastics
      distribution and likely reflecting a complex interplay between pollution sources,
      sinks and residence times of different polymers at sea.

PMID- 27876840
TI  - Transcriptome profiling shows gene regulation patterns in ginsenoside pathway in
      response to methyl jasmonate in Panax Quinquefolium adventitious root.
AB  - Here, we combine elicitors and transcriptomics to investigate the inducible
      biosynthesis of the ginsenoside from the Panax quinquefolium. Treatment of P.
      quinquefolium adventitious root with methyl jasmonate (MJ) results in an increase
      in ginsenoside content (43.66 mg/g compared to 8.32 mg/g in control group).
      Therefore, we sequenced the transcriptome of native and MJ treated adventitious
      root in order to elucidate the key differentially expressed genes (DEGs) in the
      ginsenoside biosynthetic pathway. Through DEG analysis, we found that 5,759
      unigenes were up-regulated and 6,389 unigenes down-regulated in response to MJ
      treatment. Several defense-related genes (48) were identified, participating in
      salicylic acid (SA), jasmonic acid (JA), nitric oxide (NO) and abscisic acid
      (ABA) signal pathway. Additionally, we mapped 72 unigenes to the ginsenoside
      biosynthetic pathway. Four cytochrome P450s (CYP450) were likely to catalyze
      hydroxylation at C-16 (c15743_g1, c39772_g1, c55422_g1) and C-30 (c52011_g1) of
      the triterpene backbone. UDP-xylose synthases (c52571_g3) was selected as the
      candidate, which was likely to involve in ginsenoside Rb3 biosynthesis.

PMID- 27876822
TI  - A principal component meta-analysis on multiple anthropometric traits identifies
      novel loci for body shape.
AB  - Large consortia have revealed hundreds of genetic loci associated with
      anthropometric traits, one trait at a time. We examined whether genetic variants
      affect body shape as a composite phenotype that is represented by a combination
      of anthropometric traits. We developed an approach that calculates averaged PCs
      (AvPCs) representing body shape derived from six anthropometric traits (body mass
      index, height, weight, waist and hip circumference, waist-to-hip ratio). The
      first four AvPCs explain >99% of the variability, are heritable, and associate
      with cardiometabolic outcomes. We performed genome-wide association analyses for
      each body shape composite phenotype across 65 studies and meta-analysed summary
      statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1,
      RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our
      findings highlight the value of using multiple traits to define complex
      phenotypes for discovery, which are not captured by single-trait analyses, and
      may shed light onto new pathways.

PMID- 27876839
TI  - Antibacterial ability and hemocompatibility of graphene functionalized germanium.
AB  - Germanium (Ge), as an elemental semiconductor material, has been an attractive
      candidate for manufacturing semiconductor microelectronic device. In the present
      investigation, to improve the biocompatibility of Ge-based device, graphene film
      is directly deposited on the Ge surface with different coverage area by
      controlling the growth time. Compared to bare Ge, the presence of graphene film
      entitles Ge with satisfactory antibacterial ability against Staphylococcus aureus
      (S.aureus), and acceptable antibacterial ability against Escherichia coli (E.
      coli). Meanwhile, antibacterial efficiency closely correlates with coverage area
      of graphene film, and larger graphene coverage always leads to better
      antibacterial performance. The underlying mechanism is thought to be the
      integrative action of phospholipids disturbance and electron extraction at the
      interface between graphene and biomembrane. Meanwhile, the electron extraction
      action would further lead to the activation of platelet. This study might provide
      some new insights into the relationship between antibacterial ability and
      hemocompatibility based on graphene functionalized biomedical device.

PMID- 27876841
TI  - Accuracy of pulse interval timing in ambulatory blood pressure measurement.
AB  - Blood pressure (BP) monitors rely on pulse detection. Some blood pressure
      monitors use pulse timings to analyse pulse interval variability for arrhythmia
      screening, but this assumes that the pulse interval timings detected from BP
      cuffs are accurate compared with RR intervals derived from ECG. In this study we
      compared the accuracy of pulse intervals detected using an ambulatory blood
      pressure monitor (ABPM) with single lead ECG. Twenty participants wore an ABPM
      for three hours and a data logger which synchronously measured cuff pressure and
      ECG. RR intervals were compared with corresponding intervals derived from the
      cuff pressure tracings using three different pulse landmarks. Linear mixed
      effects models were used to assess differences between ECG and cuff pressure
      timings and to investigate the effect of potential covariates. In addition, the
      maximum number of successive oscillometric beats detectable in a measurement was
      assessed. From 243 BP measurements, the landmark at the foot of the oscillometric
      pulse was found to be associated with fewest covariates and had a random error of
      9.5 ms. 99% of the cuff pressure recordings had more than 10 successive
      detectable oscillometric beats. RR intervals can be accurately estimated using an
      ABPM.

PMID- 27876842
TI  - Edge effects reverse facilitation by a widespread foundation species.
AB  - Dense aggregations of foundation species often mitigate environmental stresses
      for organisms living among them. Considerable work documents such benefits by
      comparing conditions inside versus outside these biogenic habitats. However,
      environmental gradients commonly arise across the extent of even single patches
      of habitat-forming species, including cases where stresses diverge between
      habitat interiors and edges. We ask here whether such edge effects could alter
      how habitat-forming species influence residents, potentially changing the
      strength or direction of interactions (i.e., from stress amelioration to
      exacerbation). We take as a model system the classic marine foundation species,
      Mytilus californianus, the California mussel. Results demonstrate that mussel
      beds both increase and decrease thermal stresses. Over a distance of 6 to 10 cm
      from the bed interior to its upper surface, peak temperatures climb from as much
      as 20  degrees C below to 5  degrees C above those of adjacent bedrock. This
      directional shift in temperature modification affects interactions with juvenile
      mussels, such that thermal stresses and associated mortality risk are higher at
      the bed surface, but substantially reduced deeper within the adult matrix. These
      findings provide a case example of how stress gradients generated across biogenic
      habitats can markedly alter ecological interactions even within a single habitat
      patch.

PMID- 27876843
TI  - Experienced migratory songbirds do not display goal-ward orientation after
      release following a cross-continental displacement: an automated telemetry study.
AB  - The ability to navigate implies that animals have the capability to compensate
      for geographical displacement and return to their initial goal or target.
      Although some species are capable of adjusting their direction after
      displacement, the environmental cues used to achieve this remain elusive. Two
      possible cues are geomagnetic parameters (magnetic map hypothesis) or atmospheric
      odour-forming gradients (olfactory map hypothesis). In this study, we examined
      both of these hypotheses by surgically deactivating either the magnetic or
      olfactory sensory systems in experienced white-throated sparrows (Zonotrichia
      albicollis) captured in southern Ontario, Canada, during spring migration.
      Treated, sham-treated, and intact birds were then displaced 2,200 km west to
      Saskatchewan, Canada. Tracking their initial post-displacement migration using an
      array of automated VHF receiving towers, we found no evidence in any of the
      groups for compensatory directional response towards their expected breeding
      grounds. Our results suggest that white-throated sparrows may fall back to a
      simple constant-vector orientation strategy instead of performing true navigation
      after they have been geographically displaced to an unfamiliar area during spring
      migration. Such a basic strategy may be more common than currently thought in
      experienced migratory birds and its occurrence could be determined by habitat
      preferences or range size.

PMID- 27876845
TI  - Non-label immune cell state prediction using Raman spectroscopy.
AB  - The acquired immune system, mainly composed of T and B lymphocytes, plays a key
      role in protecting the host from infection. It is important and technically
      challenging to identify cell types and their activation status in living and
      intact immune cells, without staining or killing the cells. Using Raman
      spectroscopy, we succeeded in discriminating between living T cells and B cells,
      and visualized the activation status of living T cells without labeling. Although
      the Raman spectra of T cells and B cells were similar, they could be
      distinguished by discriminant analysis of the principal components. Raman spectra
      of activated T cells with anti-CD3 and anti-CD28 antibodies largely differed
      compared to that of naive T cells, enabling the prediction of T cell activation
      status at a single cell level. Our analysis revealed that the spectra of
      individual T cells gradually change from the pattern of naive T cells to that of
      activated T cells during the first 24 h of activation, indicating that changes in
      Raman spectra reflect slow changes rather than rapid changes in cell state during
      activation. Our results indicate that the Raman spectrum enables the detection of
      dynamic changes in individual cell state scattered in a heterogeneous population.

PMID- 27876844
TI  - The N-terminal loop of IRAK-4 death domain regulates ordered assembly of the
      Myddosome signalling scaffold.
AB  - Activation of Toll-like receptors induces dimerization and the recruitment of the
      death domain (DD) adaptor protein MyD88 into an oligomeric post receptor complex
      termed the Myddosome. The Myddosome is a hub for inflammatory and oncogenic
      signaling and has a hierarchical arrangement with 6-8 MyD88 molecules assembling
      with exactly 4 of IRAK-4 and 4 of IRAK-2. Here we show that a conserved motif in
      IRAK-4 (Ser8-X-X-X-Arg12) is autophosphorylated and that the phosphorylated DD is
      unable to form Myddosomes. Furthermore a mutant DD with the phospho-mimetic
      residue Asp at this position is impaired in both signalling and Myddosome
      assembly. IRAK-4 Arg12 is also essential for Myddosome assembly and signalling
      and we propose that phosphorylated Ser8 induces the N-terminal loop to fold into
      an alpha-helix. This conformer is stabilised by an electrostatic interaction
      between phospho-Ser8 and Arg12 and would destabilise a critical interface between
      IRAK-4 and MyD88. Interestingly IRAK-2 does not conserve this motif and has an
      alternative interface in the Myddosome that requires Arg67, a residue conserved
      in paralogues, IRAK-1 and 3(M).

PMID- 27876846
TI  - Generation of macroscopic Schrodinger cat state in diamond mechanical resonator.
AB  - We propose a scheme to generate macroscopic Schrodinger cat state (SCS) in
      diamond mechanical resonator (DMR) via the dynamical strain-mediated coupling
      mechanism. In our model, the direct coupling between the nitrogen-vacancy (NV)
      center and lattice strain field enables coherent spin-phonon interactions in the
      quantum regime. Based on a cyclic Delta-type transition structure of the NV
      center constructed by combining the quantized mechanical strain field and a pair
      of external microwave fields, the populations of the different energy levels can
      be selectively transferred by controlling microwave fields, and the SCS can be
      created by adjusting the controllable parameters of the system. Furthermore, we
      demonstrate the nonclassicality of the mechanical SCS both in non-dissipative
      case and dissipative case. The experimental feasibility and challenge are
      justified using currently available technology.

PMID- 27876847
TI  - A simplified computational memory model from information processing.
AB  - This paper is intended to propose a computational model for memory from the view
      of information processing. The model, called simplified memory information
      retrieval network (SMIRN), is a bi-modular hierarchical functional memory network
      by abstracting memory function and simulating memory information processing. At
      first meta-memory is defined to express the neuron or brain cortices based on the
      biology and graph theories, and we develop an intra-modular network with the
      modeling algorithm by mapping the node and edge, and then the bi-modular network
      is delineated with intra-modular and inter-modular. At last a polynomial
      retrieval algorithm is introduced. In this paper we simulate the memory phenomena
      and functions of memorization and strengthening by information processing
      algorithms. The theoretical analysis and the simulation results show that the
      model is in accordance with the memory phenomena from information processing
      view.

PMID- 27876848
TI  - Novel structure in sciaenid fish skulls indicates continuous production of the
      cephalic neuromast cupula.
AB  - The presence of a conspicuous and frequent but never-described structure in the
      skull cavities of sciaenid fish was noted during population studies in an
      urbanized bay. The ultrastructure closely resembles the cupula of neuromasts, an
      organ associated with the perception of the environment in teleost fish. The
      bodies were recorded detached in both preserved and freshly sampled individuals
      and without associated cilia. Prominent characteristics are acellularity, the
      elliptic-conic shape composed of stack-like protein lamellas, and a mesh-like
      appearance in cross section. These acellular lamellar cephalic bodies (ALCBs)
      were more abundant in larger individuals and showed temporal peaks of abundance
      independently of the fish size. The conic and lamellar features suggest that the
      deposition of protein layers follows fish growth, and the bimodality of the size
      of these structures in individuals indicates temporal peaks of production. These
      results indicate that these ALCBs are a consequence of the accretion of the
      cupula of neuromasts at a faster rate than they degrade. Given the novelty of
      this structure and the increasing records of diseases of marine organisms
      worldwide, an important question is whether these bodies occur subsequently to
      some environmental change and whether their accumulation in the skull cavities
      has consequences to fish health.

PMID- 27876850
TI  - DNA barcoding of Mobulid Ray Gill Rakers for Implementing CITES on Elasmobranch
      in China.
AB  - The Convention on International Trade in Endangered Species of Wild Fauna and
      Flora (CITES) has been counted on for conserving threatened marine fish since it
      regulates the commercial international trade of these species. Implementation of
      the international treaty for Mantas included on CITES Appendix II is challenging
      due to insufficient information on species identification and markets management.
      To fill the gap in such aspects, we identified five species of Mobulid rays
      (Mobula spps. and Manta spp) by using COI and NADH2 mtDNA markers in dried ray
      gill rakers from Chinese markets, namely, Mobula japonica (representing 54.8% of
      the sample set), M. tarapacana (14.4%), M. kuhlii (13.3%), M. thurstoni (6.4%),
      along with Manta birostris (11.2%; CITES Appendix II). The utilization and
      conservation statuses of these species were discussed. Based on combination of
      DNA barcodes and key morphological characters, we developed a three-step process
      for identifying the gill rakers of Mobulid rays which has been adopted by
      frontline enforcement in China. We hope that our work can serve as a foundation
      and basis to reinforce objectives of international treaties, regulation of
      consumer-driven markets, regional cooperation, and national fishery management on
      endangered elasmobranchs in China as well as related countries.

PMID- 27876849
TI  - Characterization of two distinct early post-entry blocks to HIV-1 in common
      marmoset lymphocytes.
AB  - In nature, primate lentiviruses infect humans and several Old World monkeys and
      apes. However, to date, lentiviruses infecting New World monkeys have not been
      described. We studied the susceptibility of common marmoset cells to HIV-1
      infection and observed the presence of post-entry blocks to the early phase of
      HIV-1 infection in peripheral blood lymphocytes (PBLs) and a B lymphocytic cell
      line (B-LCL). The blocks present in these cells are dominant and phenotypically
      different from each other. In PBLs, the block occurs at the level of reverse
      transcription, reducing the accumulation of early and late transcripts, similar
      to the block imposed by TRIM5alpha. However, we have found that marmoset
      TRIM5alpha does not block HIV-1. In contrast, the restriction factor present in B
      LCLs blocks HIV-1 replication at a later step, after nuclear entry, and inhibits
      integration. Additionally, we have identified an HIV-1 capsid mutant, N74D, that
      is able to escape the restriction in the marmoset B-LCLs. Our results suggest
      that the factors responsible for the blocks present in marmoset PBLs and B-LCLs
      are different. We propose the existence of at least two new restriction factors
      able to block HIV-1 infection in marmoset lymphocytes.

PMID- 27876852
TI  - Relative abundance and distribution of fisheries influence risk of seabird
      bycatch.
AB  - Fisheries provide an abundant and predictable food source for many pelagic
      seabirds through discards, but also pose a major threat to them through bycatch,
      threatening their populations worldwide. The reform of the European Common
      Fisheries Policy (CFP), which intends to ban discards through the landing
      obligation of all catches, may force seabirds to seek alternative food sources,
      such as baited hooks from longlines, increasing bycatch rates. To test this
      hypothesis we performed a combined analysis of seabird-fishery interactions using
      as a model Scopoli's shearwaters Calonectris diomedea in the Mediterranean.
      Tracking data showed that the probability of shearwaters attending longliners
      increased exponentially with a decreasing density of trawlers. On-board
      observations and mortality events corroborated this result: the probability of
      birds attending longliners increased 4% per each trawler leaving the longliner
      proximity and bird mortality increased tenfold when trawlers were not operating.
      Therefore, the implementation of the landing obligation in EU waters will likely
      cause a substantial increase in bycatch rates in longliners, at least in the
      short-term, due to birds switching from trawlers to longliners. Thus the
      implementation of the landing obligation must be carefully monitored and
      counterbalanced with an urgent implementation of bycatch mitigation measures in
      the longline fleet.

PMID- 27876851
TI  - The genome, transcriptome, and proteome of the nematode Steinernema carpocapsae:
      evolutionary signatures of a pathogenic lifestyle.
AB  - The entomopathogenic nematode Steinernema carpocapsae has been widely used for
      the biological control of insect pests. It shares a symbiotic relationship with
      the bacterium Xenorhabdus nematophila, and is emerging as a genetic model to
      study symbiosis and pathogenesis. We obtained a high-quality draft of the
      nematode's genome comprising 84,613,633 bp in 347 scaffolds, with an N50 of 1.24
      Mb. To improve annotation, we sequenced both short and long RNA and conducted
      shotgun proteomic analyses. S. carpocapsae shares orthologous genes with other
      parasitic nematodes that are absent in the free-living nematode C. elegans, it
      has ncRNA families that are enriched in parasites, and expresses proteins
      putatively associated with parasitism and pathogenesis, suggesting an active role
      for the nematode during the pathogenic process. Host and parasites might engage
      in a co-evolutionary arms-race dynamic with genes participating in their
      interaction showing signatures of positive selection. Our analyses indicate that
      the consequence of this arms race is better characterized by positive selection
      altering specific functions instead of just increasing the number of positively
      selected genes, adding a new perspective to these co-evolutionary theories. We
      identified a protein, ATAD-3, that suggests a relevant role for mitochondrial
      function in the evolution and mechanisms of nematode parasitism.

PMID- 27876853
TI  - Collagen cross-linking: insights on the evolution of metazoan extracellular
      matrix.
AB  - Collagens constitute a large family of extracellular matrix (ECM) proteins that
      play a fundamental role in supporting the structure of various tissues in
      multicellular animals. The mechanical strength of fibrillar collagens is highly
      dependent on the formation of covalent cross-links between individual fibrils, a
      process initiated by the enzymatic action of members of the lysyl oxidase (LOX)
      family. Fibrillar collagens are present in a wide variety of animals, therefore
      often being associated with metazoan evolution, where the emergence of an
      ancestral collagen chain has been proposed to lead to the formation of different
      clades. While LOX-generated collagen cross-linking metabolites have been detected
      in different metazoan families, there is limited information about when and how
      collagen acquired this particular modification. By analyzing telopeptide and
      helical sequences, we identified highly conserved, potential cross-linking sites
      throughout the metazoan tree of life. Based on this analysis, we propose that
      they have importantly contributed to the formation and further expansion of
      fibrillar collagens.

PMID- 27876854
TI  - miR-706 inhibits the oxidative stress-induced activation of PKCalpha/TAOK1 in
      liver fibrogenesis.
AB  - Oxidative stress induces the activation of liver fibrogenic cells
      (myofibroblasts), thus promoting the expression of fibrosis-related genes,
      leading to hepatic fibrogenesis. MicroRNAs (miRNAs) are a new class of small RNAs
      ~18-25 nucleotides in length involved in post-transcriptional regulation of gene
      expression. Wound-healing and remodeling processes in liver fibrosis have been
      associated with changes in hepatic miRNA expression. However, the role of miR-706
      in liver fibrogenesis is currently unknown. In the present study, we show that
      miR-706 is abundantly expressed in hepatocytes. Moreover, oxidative stress leads
      to a significant downregulation of miR-706, and the further reintroduction of miR
      706 inhibits oxidative stress-induced expression of fibrosis-related markers such
      as alpha-SMA. Subsequent studies revealed that miR-706 directly inhibits PKCalpha
      and TAOK1 expression via binding to the 3'-untranslated region, preventing
      epithelial mesenchymal transition. In vivo studies showed that intravenous
      injection of miR-706 agomir successfully increases hepatic miR-706 and decreases
      alpha-SMA, PKCalpha, and TAOK1 protein levels in livers of carbon tetrachloride
      (CCl4)-treated mice. In summary, this study reveals a protective role for miR-706
      by blocking the oxidative stress-induced activation of PKCalpha/TAOK1. Our
      results further identify a major implication for miR-706 in preventing hepatic
      fibrogenesis and suggest that miR-706 may be a suitable molecular target for anti
      fibrosis therapy.

PMID- 27876855
TI  - Navigation by anomalous random walks on complex networks.
AB  - Anomalous random walks having long-range jumps are a critical branch of dynamical
      processes on networks, which can model a number of search and transport
      processes. However, traditional measurements based on mean first passage time are
      not useful as they fail to characterize the cost associated with each jump. Here
      we introduce a new concept of mean first traverse distance (MFTD) to characterize
      anomalous random walks that represents the expected traverse distance taken by
      walkers searching from source node to target node, and we provide a procedure for
      calculating the MFTD between two nodes. We use Levy walks on networks as an
      example, and demonstrate that the proposed approach can unravel the interplay
      between diffusion dynamics of Levy walks and the underlying network structure.
      Moreover, applying our framework to the famous PageRank search, we show how to
      inform the optimality of the PageRank search. The framework for analyzing
      anomalous random walks on complex networks offers a useful new paradigm to
      understand the dynamics of anomalous diffusion processes, and provides a unified
      scheme to characterize search and transport processes on networks.

PMID- 27876857
TI  - Smart-aggregation imaging for single molecule localisation with SPAD cameras.
AB  - Single molecule localisation microscopy (SMLM) has become an essential part of
      the super-resolution toolbox for probing cellular structure and function. The
      rapid evolution of these techniques has outstripped detector development and
      faster, more sensitive cameras are required to further improve localisation
      certainty. Single-photon avalanche photodiode (SPAD) array cameras offer single
      photon sensitivity, very high frame rates and zero readout noise, making them a
      potentially ideal detector for ultra-fast imaging and SMLM experiments. However,
      performance traditionally falls behind that of emCCD and sCMOS devices due to
      lower photon detection efficiency. Here we demonstrate, both experimentally and
      through simulations, that the sensitivity of a binary SPAD camera in SMLM
      experiments can be improved significantly by aggregating only frames containing
      signal, and that this leads to smaller datasets and competitive performance with
      that of existing detectors. The simulations also indicate that with predicted
      future advances in SPAD camera technology, SPAD devices will outperform existing
      scientific cameras when capturing fast temporal dynamics.

PMID- 27876858
TI  - Multi-Functional Carbon Fibre Composites using Carbon Nanotubes as an Alternative
      to Polymer Sizing.
AB  - Carbon fibre reinforced polymers (CFRP) were introduced to the aerospace,
      automobile and civil engineering industries for their high strength and low
      weight. A key feature of CFRP is the polymer sizing - a coating applied to the
      surface of the carbon fibres to assist handling, improve the interfacial adhesion
      between fibre and polymer matrix and allow this matrix to wet-out the carbon
      fibres. In this paper, we introduce an alternative material to the polymer
      sizing, namely carbon nanotubes (CNTs) on the carbon fibres, which in addition
      imparts electrical and thermal functionality. High quality CNTs are grown at a
      high density as a result of a 35 nm aluminium interlayer which has previously
      been shown to minimise diffusion of the catalyst in the carbon fibre substrate. A
      CNT modified-CFRP show 300%, 450% and 230% improvements in the electrical
      conductivity on the 'surface', 'through-thickness' and 'volume' directions,
      respectively. Furthermore, through-thickness thermal conductivity calculations
      reveal a 107% increase. These improvements suggest the potential of a direct
      replacement for lightning strike solutions and to enhance the efficiency of
      current de-icing solutions employed in the aerospace industry.

PMID- 27876856
TI  - The trend and the disease prediction of vascular endothelial growth factor and
      placenta growth factor in nontuberculous mycobacterial lung disease.
AB  - Nontuberculous mycobacteria (NTM)-lung disease (LD) is an increasing health
      problem worldwide. The diagnosis of this disease remains difficult, however the
      application of placenta growth factor (PlGF) and vascular endothelial growth
      factor (VEGF) has not yet been studied. We screened patients with Mycobacterium
      avium complex or M. abscessus isolated from sputum, and enrolled 32 patients with
      NTM-LD and 93 with NTM pulmonary colonization. The NTM-LD group had a lower body
      mass index, higher proportion of bronchiectasis, more respiratory symptoms and
      pulmonary lesions, and higher titers of sputum acid-fast stain than the NTM
      pulmonary colonization group. The plasma level of PlGF was lower in the NTM-LD
      group than in the NTM colonization group, whereas the level of VEGF was higher in
      the NTM-LD group. In multivariable logistic regression analysis excluding NTM
      cultures, the predictive model for NTM-LD included sputum AFS titer, a nodular
      bronchiectasis radiographic pattern, plasma VEGF/PlGF ratio, and chest
      radiographic score (VEGF/P1GF ratio became not significant as a factor in
      multivariable generalized linear model). The four-factor predictive index had
      good positive likelihood ratio and negative likelihood ratio for predicting NTM
      LD in the patients with NTM in their sputum.

PMID- 27876860
TI  - Possible generation of heat from nuclear fusion in Earth's inner core.
AB  - The cause and source of the heat released from Earth's interior have not yet been
      determined. Some research groups have proposed that the heat is supplied by
      radioactive decay or by a nuclear georeactor. Here we postulate that the
      generation of heat is the result of three-body nuclear fusion of deuterons
      confined in hexagonal FeDx core-centre crystals; the reaction rate is enhanced by
      the combined attraction effects of high-pressure (~364 GPa) and high-temperature
      (~5700 K) and by the physical catalysis of neutral pions: 2D + 2D + 2D -> 21H +
      4He + 2  + 20.85 MeV. The possible heat generation rate can be calculated as 8.12
      * 1012 J/m3, based on the assumption that Earth's primitive heat supply has
      already been exhausted. The H and He atoms produced and the anti-neutrino are
      incorporated as Fe-H based alloys in the H-rich portion of inner core, are
      released from Earth's interior to the universe, and pass through Earth,
      respectively.

PMID- 27876859
TI  - Negative Magnetoresistance in Amorphous Indium Oxide Wires.
AB  - We study magneto-transport properties of several amorphous Indium oxide nanowires
      of different widths. The wires show superconducting transition at zero magnetic
      field, but, there exist a finite resistance at the lowest temperature. The R(T)
      broadening was explained by available phase slip models. At low field, and far
      below the superconducting critical temperature, the wires with diameter equal to
      or less than 100 nm, show negative magnetoresistance (nMR). The magnitude of nMR
      and the crossover field are found to be dependent on both temperature and the
      cross-sectional area. We find that this intriguing behavior originates from the
      interplay between two field dependent contributions.

PMID- 27876861
TI  - Origin of long-lived quantum coherence and excitation dynamics in pigment-protein
      complexes.
AB  - We explore the mechanism for the long-lived quantum coherence by considering the
      discrete phonon modes: these vibrational modes effectively weaken the exciton
      environment interaction, due to the new composite (polaron) formed by excitons
      and vibrons. This subsequently demonstrates the role of vibrational coherence
      which greatly contributes to long-lived feature of the excitonic coherence that
      has been observed in femtosecond experiments. The estimation of the timescale of
      coherence elongated by vibrational modes is given in an analytical manner. To
      test the validity of our theory, we study the pigment-protein complex in detail
      by exploring the energy transfer and coherence dynamics. The ground-state
      vibrational coherence generated by incoherent radiations is shown to be long
      survived and is demonstrated to be significant in promoting the excitation energy
      transfer. This is attributed to the nonequilibriumness of the system caused by
      the detailed-balance-breaking, which funnels the downhill migration of excitons.

PMID- 27876862
TI  - In Silico Exploration for Novel Type-I Inhibitors of Tie-2/TEK: The Performance
      of Different Selection Strategy in Selecting Virtual Screening Candidates.
AB  - The receptor tyrosine kinase Tie-2 is involved in vessel remodeling and
      maturation, and has been regarded as a potential target for the treatment of
      various solid tumors. The absence of novel, potent and selective inhibitors
      severely hampers the understanding of the therapeutic potential of Tie-2. In the
      present work, we describe the discovery of novel type-I inhibitors of Tie-2 by
      structure-based virtual screening. Preliminary SAR was also performed based on
      one active compound, and several novel inhibitors with low micro-molar affinity
      were discovered. To directly compare the efficiency between different filtering
      strategies in selecting VS candidates, two methods were separately carried out to
      screen the same chemical library, and the selected VS candidates were then
      experimentally assessed by in vitro enzymatic assays. The results demonstrate
      that the hit rate is improved when stricter drug-likeness criteria and less
      number of molecules for clustering analysis are used, and meanwhile, the
      molecular diversity of the compounds still maintains. As a case study of TIE-2,
      the information presented in this work underscores the importance of selecting an
      appropriate selection strategy in VS campaign, and the novel inhibitors
      identified and the detailed binding modes of action provide a starting point for
      further hit-to-lead optimization process.

PMID- 27876863
TI  - Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1
      dependent mechanism for crypt restitution following radiation injury.
AB  - Crypt epithelial survival and regeneration after injury require highly
      coordinated complex interplay between resident stem cells and diverse cell types.
      The function of Dclk1 expressing tuft cells regulating intestinal epithelial DNA
      damage response for cell survival/self-renewal after radiation-induced injury is
      unclear. Intestinal epithelial cells (IECs) were isolated and purified and
      utilized for experimental analysis. We found that small intestinal crypts of
      VillinCre;Dclk1f/f mice were hypoplastic and more apoptotic 24 h post-total body
      irradiation, a time when stem cell survival is p53-independent. Injury-induced
      ATM mediated DNA damage response, pro-survival genes, stem cell markers, and self
      renewal ability for survival and restitution were reduced in the isolated
      intestinal epithelial cells. An even greater reduction in these signaling
      pathways was observed 3.5 days post-TBI, when peak crypt regeneration occurs. We
      found that interaction with Dclk1 is critical for ATM and COX2 activation in
      response to injury. We determined that Dclk1 expressing tuft cells regulate the
      whole intestinal epithelial cells following injury through paracrine mechanism.
      These findings suggest that intestinal tuft cells play an important role in
      regulating the ATM mediated DNA damage response, for epithelial cell
      survival/self-renewal via a Dclk1 dependent mechanism, and these processes are
      indispensable for restitution and function after severe radiation-induced injury.

PMID- 27876865
TI  - Increased gene dosage for beta- and kappa-casein in transgenic cattle improves
      milk composition through complex effects.
AB  - We have previously generated transgenic cattle with additional copies of bovine
      beta- and kappa casein genes. An initial characterisation of milk produced with a
      hormonally induced lactation from these transgenic cows showed an altered milk
      composition with elevated beta-casein levels and twofold increased kappa-casein
      content. Here we report the first in-depth characterisation of the composition of
      the enriched casein milk that was produced through a natural lactation. We have
      analyzed milk from the high expressing transgenic line TG3 for milk composition
      at early, peak, mid and late lactation. The introduction of additional beta- and
      kappa-casein genes resulted in the expected expression of the transgene derived
      proteins and an associated reduction in the size of the casein micelles.
      Expression of the transgenes was associated with complex changes in the
      expression levels of other milk proteins. Two other major milk components were
      affected, namely fat and micronutrients. In addition, the sialic acid content of
      the milk was increased. In contrast, the level of lactose remained unchanged.
      This novel milk with its substantially altered composition will provide insights
      into the regulatory processes synchronizing the synthesis and assembly of milk
      components, as well as production of potentially healthier milk with improved
      dairy processing characteristics.

PMID- 27876864
TI  - Identification of an infectious bronchitis coronavirus strain exhibiting a
      classical genotype but altered antigenicity, pathogenicity, and innate immunity
      profile.
AB  - Avian coronavirus infectious bronchitis virus (IBV) poses economic threat to the
      poultry industry worldwide. Pathogenic IBV 3575/08 was isolated from broilers
      vaccinated with the attenuated viral vaccine derived from a Taiwan strain
      2575/98. In this study, extensive investigations were conducted on the genome
      sequences, antigenicity, pathogenicity, and host immune responses of several IBV
      strains in specific-pathogen-free chickens. Sequence analyses revealed that
      3575/08 and 2575/98 shared high homology in their structural genes, but not in
      non-structural accessory proteins such as 3a, 3b and 5b. Despite a high degree of
      homology in their spike protein genes, cross neutralization test showed low cross
      protection between 3575/08 and 2575/98, suggesting distinct antigenicity for the
      two strains. Animal challenge experiments exhibited strong respiratory and renal
      pathogenicity for 3575/08. In addition, early and prolonged viral shedding and
      rapid viral dissemination were observed. Immune gene expression profiling by PCR
      array showed chickens infected with 3575/08 had delayed expression of a subset of
      early innate immune genes, whereas chickens infected with the wild-type or
      attenuated-type 2575/08 revealed quick gene induction and efficient virus
      control. In summary, this study reveals a new IBV strain, which harbors a known
      local genotype but displays remarkably altered antigenicity, pathogenicity and
      host defenses.

PMID- 27876867
TI  - Active Brownian particles and run-and-tumble particles separate inside a maze.
AB  - A diverse range of natural and artificial self-propelled particles are known and
      are used nowadays. Among them, active Brownian particles (ABPs) and run-and
      tumble particles (RTPs) are two important classes. We numerically study non
      interacting ABPs and RTPs strongly confined to different maze geometries in two
      dimensions. We demonstrate that by means of geometrical confinement alone, ABPs
      are separable from RTPs. By investigating Matryoshka-like mazes with nested
      shells, we show that a circular maze has the best filtration efficiency. Results
      on the mean first-passage time reveal that ABPs escape faster from the center of
      the maze, while RTPs reach the center from the rim more easily. According to our
      simulations and a rate theory, which we developed, ABPs in steady state
      accumulate in the outermost region of the Matryoshka-like mazes, while RTPs
      occupy all locations within the maze with nearly equal probability. These results
      suggest a novel technique for separating different types of self-propelled
      particles by designing appropriate confining geometries without using chemical or
      biological agents.

PMID- 27876868
TI  - Room temperature electrically tunable rectification magnetoresistance in Ge-based
      Schottky devices.
AB  - Electrical control of magnetotransport properties is crucial for device
      applications in the field of spintronics. In this work, as an extension of our
      previous observation of rectification magnetoresistance, an innovative technique
      for electrical control of rectification magnetoresistance has been developed by
      applying direct current and alternating current simultaneously to the Ge-based
      Schottky devices, where the rectification magnetoresistance could be remarkably
      tuned in a wide range. Moreover, the interface and bulk contribution to the
      magnetotransport properties has been effectively separated based on the
      rectification magnetoresistance effect. The state-of-the-art electrical
      manipulation technique could be adapt to other similar heterojunctions, where
      fascinating rectification magnetoresistance is worthy of expectation.

PMID- 27876866
TI  - Developmental disruption of perineuronal nets in the medial prefrontal cortex
      after maternal immune activation.
AB  - Maternal infection during pregnancy increases the risk of offspring developing
      schizophrenia later in life. Similarly, animal models of maternal immune
      activation (MIA) induce behavioural and anatomical disturbances consistent with a
      schizophrenia-like phenotype in offspring. Notably, cognitive impairments in
      tasks dependent on the prefrontal cortex (PFC) are observed in humans with
      schizophrenia and in offspring after MIA during pregnancy. Recent studies of post
      mortem tissue from individuals with schizophrenia revealed deficits in
      extracellular matrix structures called perineuronal nets (PNNs), particularly in
      PFC. Given these findings, we examined PNNs over the course of development in a
      well-characterized rat model of MIA using polyinosinic-polycytidylic acid
      (polyI:C). We found selective reductions of PNNs in the PFC of polyI:C offspring
      which did not manifest until early adulthood. These deficits were not associated
      with changes in parvalbumin cell density, but a decrease in the percentage of
      parvalbumin cells surrounded by a PNN. Developmental expression of PNNs was also
      significantly altered in the amygdala of polyI:C offspring. Our results indicate
      MIA causes region specific developmental abnormalities in PNNs in the PFC of
      offspring. These findings confirm the polyI:C model replicates neuropathological
      alterations associated with schizophrenia and may identify novel mechanisms for
      cognitive and emotional dysfunction in the disorder.

PMID- 27876869
TI  - Discerning the Location and Nature of Coke Deposition from Surface to Bulk of
      Spent Zeolite Catalysts.
AB  - The formation of carbonaceous deposits (coke) in zeolite pores during catalysis
      leads to temporary deactivation of catalyst, necessitating regeneration steps,
      affecting throughput, and resulting in partial permanent loss of catalytic
      efficiency. Yet, even to date, the coke molecule distribution is quite
      challenging to study with high spatial resolution from surface to bulk of the
      catalyst particles at a single particle level. To address this challenge we
      investigated the coke molecules in HZSM-5 catalyst after ethanol conversion
      treatment by a combination of C K-edge X-ray absorption spectroscopy (XAS), 13C
      Cross polarization-magic angle spinning nuclear magnetic resonance (CP-MAS NMR)
      spectroscopy, and atom probe tomography (APT). XAS and NMR highlighted the
      aromatic character of coke molecules. APT permitted the imaging of the spatial
      distribution of hydrocarbon molecules located within the pores of spent HZSM-5
      catalyst from surface to bulk at a single particle level. 27Al NMR results and
      APT results indicated association of coke molecules with Al enriched regions
      within the spent HZSM-5 catalyst particles. The experimental results were
      additionally validated by a level-set-based APT field evaporation model. These
      results provide a new approach to investigate catalytic deactivation due to
      hydrocarbon coking or poisoning of zeolites at an unprecedented spatial
      resolution.

PMID- 27876870
TI  - Radiocaesium partitioning in Japanese cedar forests following the "early" phase
      of Fukushima fallout redistribution.
AB  - Our study focused on radiocaesium (137Cs) partitioning in forests, three
      vegetation periods after the Fukushima Daiichi nuclear power plant accident.
      137Cs distribution in forest components (organic and mineral soil layers as well
      as tree compartments: stem, bark, needles, branches and roots) was measured for
      two Japanese cedar stand ages (17 and 33 years old). The results showed that
      around 85% of the initial deposit was found in the forest floor and topsoil. For
      the youngest stand almost 70% of the deposit is present in the forest floor,
      whereas for the oldest stand 50% is present in the 0-3 cm mineral soil layer. For
      trees, old and perennial organs (including dead and living needles and branches,
      litter fall and outer bark) directly exposed to the fallout remained the most
      contaminated. The crown concentrated 61-69% of the total tree contamination.
      Surprisingly the dead organs concentrated 25 +/- 9% (young cedars) to 36 +/- 20%
      (mature cedar) of the trees' residual activity, highlighting the importance of
      that specific compartment in the early post-accident phase for Japanese cedar
      forests. Although the stem (including bark) represents the highest biomass pool,
      it only concentrates 3.3% and 4.6% of the initial 137Cs deposit for mature and
      young cedars, respectively.

PMID- 27876871
TI  - ENSO's far reaching connection to Indian cold waves.
AB  - During boreal winters, cold waves over India are primarily due to transport of
      cold air from higher latitudes. However, the processes associated with these cold
      waves are not yet clearly understood. Here by diagnosing a suite of datasets, we
      explore the mechanisms leading to the development and maintenance of these cold
      waves. Two types of cold waves are identified based on observed minimum surface
      temperature and statistical analysis. The first type (TYPE1), also the dominant
      one, depicts colder than normal temperatures covering most parts of the country
      while the second type (TYPE2) is more regional, with significant cold
      temperatures only noticeable over northwest India. Quite interestingly the first
      (second) type is associated with La Nina (El Nino) like conditions, suggesting
      that both phases of ENSO provide a favorable background for the occurrence of
      cold waves over India. During TYPE1 cold wave events, a low-level cyclonic
      anomaly generated over the Indian region as an atmospheric response to the
      equatorial convective anomalies is seen advecting cold temperatures into India
      and maintaining the cold waves. In TYPE2 cold waves, a cyclonic anomaly generated
      over west India anomalously brings cold winds to northwest India causing cold
      waves only in those parts.

PMID- 27876872
TI  - Experimental investigation into the oxidation reactivity and nanostructure of
      particulate matter from diesel engine fuelled with diesel/polyoxymethylene
      dimethyl ethers blends.
AB  - This paper focuses on oxidation reactivity and nanostructural characteristics of
      particulate matter (PM) emitted from diesel engine fuelled with different volume
      proportions of diesel/polyoxymethylene dimethyl ethers (PODEn) blends (P0, P10
      and P20). PM was collected using a metal filter from the exhaust manifold. The
      collected PM samples were characterized using thermogravimetric analysis (TGA),
      scanning electron microscopy (SEM), transmission electron microscopy (TEM) and
      Raman spectroscopy. The TGA results indicated that the PM produced by P20 had the
      highest moisture and volatility contents and the fastest oxidation rate of solid
      carbon followed by P10 and P0 derived PM. SEM analysis showed that PM generated
      from P20 was looser with a lower mean value than PM emitted from P10 and P0.
      Quantitative analysis of high-resolution TEM images presented that fringe length
      was reduced along with increased separation distance and tortuosity with an
      increase in PODEn concentration. These trends improved the oxidation reactivity.
      According to Raman spectroscopy data, the intensity, full width at half-maximum
      and intensity ratio of the bands also changed demonstrating that PM nanostructure
      disorder was correlated with a faster oxidation rate. The results show the use of
      PODEn affects the oxidation reactivity and nanostructure of PM that is easier to
      oxidize.

PMID- 27876875
TI  - Brain-inspired speech segmentation for automatic speech recognition using the
      speech envelope as a temporal reference.
AB  - Speech segmentation is a crucial step in automatic speech recognition because
      additional speech analyses are performed for each framed speech segment.
      Conventional segmentation techniques primarily segment speech using a fixed frame
      size for computational simplicity. However, this approach is insufficient for
      capturing the quasi-regular structure of speech, which causes substantial
      recognition failure in noisy environments. How does the brain handle quasi
      regular structured speech and maintain high recognition performance under any
      circumstance? Recent neurophysiological studies have suggested that the phase of
      neuronal oscillations in the auditory cortex contributes to accurate speech
      recognition by guiding speech segmentation into smaller units at different
      timescales. A phase-locked relationship between neuronal oscillation and the
      speech envelope has recently been obtained, which suggests that the speech
      envelope provides a foundation for multi-timescale speech segmental information.
      In this study, we quantitatively investigated the role of the speech envelope as
      a potential temporal reference to segment speech using its instantaneous phase
      information. We evaluated the proposed approach by the achieved information gain
      and recognition performance in various noisy environments. The results indicate
      that the proposed segmentation scheme not only extracts more information from
      speech but also provides greater robustness in a recognition test.

PMID- 27876873
TI  - The Effect of Silica Nanoparticles on Human Corneal Epithelial Cells.
AB  - Ocular drug delivery is an interesting field in current research. Silica
      nanoparticles (SiNPs) are promising drug carriers for ophthalmic drug delivery.
      However, little is known about the toxicity of SiNPs on ocular surface cells such
      as human corneal epithelial cells (HCECs). In this study, we evaluated the
      cytotoxicity induced by 50, 100 and 150 nm sizes of SiNPs on cultured HCECs for
      up to 48 hours. SiNPs were up-taken by HCECs inside cytoplasmic vacuoles.
      Cellular reactive oxygen species generation was mildly elevated, dose
      dependently, with SiNPs, but no significant decrease of cellular viability was
      observed up to concentrations of 100 MUg/ml for three different sized SiNPs.
      Western blot assays revealed that both cellular autophagy and mammalian target of
      rapamycin (mTOR) pathways were activated with the addition of SiNPs. Our findings
      suggested that 50, 100 and 150 nm sized SiNPs did not induce significant
      cytotoxicity in cultured HCECs.

PMID- 27876874
TI  - TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model,
      via upregulation of GAS6, L1CAM, and Akt signalling.
AB  - Epithelial ovarian cancer (EOC) is the most deadly gynaecologic malignancy due to
      late onset of symptoms and propensity towards drug resistance. Epithelial
      mesenchymal transition (EMT) has been linked to the development of
      chemoresistance in other cancers, yet little is known regarding its role in EOC.
      In this study, we sought to determine the role of the transcription factor
      TWIST1, a master regulator of EMT, on cisplatin resistance in an EOC model. We
      created two Ovcar8-derived cell lines that differed only in their TWIST1
      expression. TWIST1 expression led to increased tumour engraftment in mice, as
      well as cisplatin resistance in vitro. RNA sequencing analysis revealed that
      TWIST1 expression resulted in upregulation of GAS6 and L1CAM and downregulation
      of HMGA2. Knockdown studies of these genes demonstrated that loss of GAS6 or
      L1CAM sensitized cells to cisplatin, but that loss of HMGA2 did not give rise to
      chemoresistance. TWIST1, in part via GAS6 and L1CAM, led to higher expression and
      activation of Akt upon cisplatin treatment, and inhibition of Akt activation
      sensitized cells to cisplatin. These results suggest TWIST1- and EMT-driven
      increase in Akt activation, and thus tumour cell proliferation, as a potential
      mechanism of drug resistance in EOC.

PMID- 27876877
TI  - Evaluation of the efficacy of Myco/F lytic system, MGIT960 system and Lowenstein
      Jensen medium for recovery of Mycobacterium tuberculosis from sterile body
      fluids.
AB  - The diagnosis of extrapulmonary tuberculosis (EPTB) is challenging due to non
      specific symptoms, invasive approach for specimen collection and most
      importantly, the paucibacillary status. The objective of this assay was to
      evaluate the efficacy of Myco/F lytic system, BACTEC Mycobacteria Growth
      Indicator Tube (MGIT) 960 system and Lowenstein-Jensen (L-J) medium for recovery
      of bacilli from sterile body fluids. 214 specimens (114 pleural fluid and 100
      pus) from clinically diagnosed EPTB patients were collected and subjected to
      Ziehl-Neelsen (ZN) smear microscopy, L-J culture, MGIT 960 culture and Myco/F
      lytic culture.103 out of the 214 sterile body fluid samples yielded positive
      culture outcomes by any of the three methods. Among all the culture positive
      specimens, the recovery rate was 86.41% for Myco/F lytic, 75.73% for MGIT 960,
      and 42.72% for L-J medium. The mean time to positivity (TTP) was 27.06 +/- 8.03
      days for Myco/F lytic, 22.20 +/- 7.84 days for MGIT960 and 42 +/- 8.84 days for L
      J medium. The rates of contamination were 6.54%, 3.74% and 2.80% for Myco/F
      lytic, MGIT960 and L-J medium respectively. Both Myco/F lytic and MGIT960 system
      were superior to L-J medium for recovery of bacilli from sterile body fluids.
      Myco/F lytic system was more favorable than MGIT960 regarding recovery rate and
      cost-effectiveness, thus can be considered as a promising alternative to MGIT960
      system for diagnosing EPTB.

PMID- 27876878
TI  - Dependence of phase configurations, microstructures and magnetic properties of
      iron-nickel (Fe-Ni) alloy nanoribbons on deoxidization temperature in hydrogen.
AB  - Iron-nickel (Fe-Ni) alloy nanoribbons were reported for the first time by
      deoxidizing NiFe2O4 nanoribbons, which were synthesized through a handy route of
      electrospinning followed by air-annealing at 450  degrees C, in hydrogen (H2) at
      different temperatures. It was demonstrated that the phase configurations,
      microstructures and magnetic properties of the as-deoxidized samples closely
      depended upon the deoxidization temperature. The spinel NiFe2O4 ferrite of the
      precursor nanoribbons were firstly deoxidized into the body-centered cubic (bcc)
      Fe-Ni alloy and then transformed into the face-centered cubic (fcc) Fe-Ni alloy
      of the deoxidized samples with the temperature increasing. When the deoxidization
      temperature was in the range of 300 ~ 500  degrees C, although each sample
      possessed its respective morphology feature, all of them completely reserved the
      ribbon-like structures. When it was further increased to 600  degrees C, the
      nanoribbons were evolved completely into the fcc Fe-Ni alloy nanochains.
      Additionally, all samples exhibited typical ferromagnetism. The saturation
      magnetization (Ms) firstly increased, then decreased, and finally increased with
      increasing the deoxidization temperature, while the coercivity (Hc) decreased
      monotonously firstly and then basically stayed unchanged. The largest Ms (~145.7
      emu.g-1) and the moderate Hc (~132 Oe) were obtained for the Fe-Ni alloy
      nanoribbons with a mixed configuration of bcc and fcc phases.

PMID- 27876876
TI  - Fabrication of functional hollow microspheres constructed from MOF shells:
      Promising drug delivery systems with high loading capacity and targeted
      transport.
AB  - An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery
      system with a high drug loading level and targeted delivery was designed and
      fabricated for the first time and applied to inhibit tumour cell growth. This
      hollow MOF targeting drug delivery system was prepared via a simple post
      synthetic surface modification procedure, starting from hollow ZIF-8 successfully
      obtained for the first time via a mild phase transformation under solvothermal
      conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for
      the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8
      was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a
      chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the
      targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF
      8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF
      8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore,
      the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory
      effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell
      viability assay. In addition, a drug release experiment in vitro indicated that
      ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained
      drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted
      drug transportation, imaging tracking and localized sustained release.

PMID- 27876879
TI  - Stimulus-induced Epileptic Spike-Wave Discharges in Thalamocortical Model with
      Disinhibition.
AB  - Epileptic absence seizure characterized by the typical 2-4 Hz spike-wave
      discharges (SWD) are known to arise due to the physiologically abnormal
      interactions within the thalamocortical network. By introducing a second
      inhibitory neuronal population in the cortical system, here we propose a modified
      thalamocortical field model to mathematically describe the occurrences and
      transitions of SWD under the mutual functions between cortex and thalamus, as
      well as the disinhibitory modulations of SWD mediated by the two different
      inhibitory interneuronal populations. We first show that stimulation can induce
      the recurrent seizures of SWD in the modified model. Also, we demonstrate the
      existence of various types of firing states including the SWD. Moreover, we can
      identify the bistable parametric regions where the SWD can be both induced and
      terminated by stimulation perturbations applied in the background resting state.
      Interestingly, in the absence of stimulation disinhibitory functions between the
      two different interneuronal populations can also both initiate and abate the SWD,
      which suggests that the mechanism of disinhibition is comparable to the effect of
      stimulation in initiating and terminating the epileptic SWD. Hopefully, the
      obtained results can provide theoretical evidences in exploring dynamical
      mechanism of epileptic seizures.

PMID- 27876881
TI  - High-Acquisition-Rate Single-Shot Pump-Probe Measurements Using Time-Stretching
      Method.
AB  - Recent advances of ultrafast spectroscopy allow the capture of an entire
      ultrafast signal waveform in a single probe shot, which greatly reduces the
      measurement time and opens the door for the spectroscopy of unrepeatable
      phenomena. However, most single-shot detection schemes rely on two-dimensional
      detectors, which limit the repetition rate of the measurement and can hinder real
      time visualization and manipulation of signal waveforms. Here, we demonstrate a
      new method to circumvent these difficulties and to greatly simplify the detection
      setup by using a long, single-mode optical fiber and a fast photodiode.
      Initially, a probe pulse is linearly chirped (the optical frequency varies
      linearly across the pulse in time), and the temporal profile of an ultrafast
      signal is then encoded in the probe spectrum. The probe pulse and encoded
      temporal dynamics are further chirped to nanosecond time scales using the
      dispersion in the optical fiber, thus, slowing down the ultrafast signal to time
      scales easily recorded with fast detectors and high-bandwidth electronics. We
      apply this method to three distinct ultrafast experiments: investigating the
      power dependence of the Kerr signal in LiNbO3, observing an irreversible
      transmission change of a phase change material, and capturing terahertz
      waveforms.

PMID- 27876880
TI  - Overexpression of SerpinE2/protease nexin-1 Contribute to Pathological Cardiac
      Fibrosis via increasing Collagen Deposition.
AB  - Although increases in cardiovascular load (pressure overload) are known to elicit
      ventricular remodeling including cardiomyocyte hypertrophy and interstitial
      fibrosis, the molecular mechanisms of pressure overload or AngII -induced cardiac
      interstitial fibrosis remain elusive. In this study, serpinE2/protease nexin-1
      was over-expressed in a cardiac fibrosis model induced by pressure-overloaded via
      transverse aortic constriction (TAC) in mouse. Knockdown of serpinE2 attenuates
      cardiac fibrosis in a mouse model of TAC. At meantime, the results showed that
      serpinE2 significantly were increased with collagen accumulations induced by
      AngII or TGF-beta stimulation in vitro. Intriguingly, extracellular collagen in
      myocardial fibroblast was reduced by knockdown of serpinE2 compared with the
      control in vitro. In stark contrast, the addition of exogenous PN-1 up-regulated
      the content of collagen in myocardial fibroblast. The MEK1/2- ERK1/2 signaling
      probably promoted the expression of serpinE2 via transcription factors Elk1 in
      myocardial fibroblast. In conclusion, stress-induced the ERK1/2 signaling pathway
      activation up-regulated serpinE2 expression, consequently led accumulation of
      collagen protein, and contributed to cardiac fibrosis.

PMID- 27876882
TI  - NR4A1 Knockdown Suppresses Seizure Activity by Regulating Surface Expression of
      NR2B.
AB  - Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of
      CREB that is a key regulator of epileptogenesis, has been implicated in a variety
      of biological processes and was previously identified as a seizure-associated
      molecule. However, the relationship between NR4A1 and epileptogenesis remains
      unclear. Here, we showed that NR4A1 protein was predominantly expressed in
      neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced
      mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti
      shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models.
      Moreover, reciprocal coimmunoprecipitation of NR4A1 and NR2B demonstrated their
      interaction. Furthermore, the expression of p-NR2B (Tyr1472) in epileptic mice
      and the expression of NR2B in the postsynaptic density (PSD) were significantly
      reduced in the lenti-shNR4A1 group, indicating that NR4A1 knockdown partly
      decreased surface NR2B by promoting NR2B internalization. These results are the
      first to indicate that the expression of NR4A1 in epileptic brain tissues may
      provide new insights into the molecular mechanisms underlying epilepsy.

PMID- 27876884
TI  - Movement of feeder-using songbirds: the influence of urban features.
AB  - Private gardens provide vital opportunities for people to interact with nature.
      The most popular form of interaction is through garden bird feeding.
      Understanding how landscape features and seasons determine patterns of movement
      of feeder-using songbirds is key to maximising the well-being benefits they
      provide. To determine these patterns we established three networks of automated
      data loggers along a gradient of greenspace fragmentation. Over a 12-month period
      we tracked 452 tagged blue tits Cyantistes caeruleus and great tits Parus major
      moving between feeder pairs 9,848 times, to address two questions: (i) Do urban
      features within different forms, and season, influence structural (presence
      absence of connections between feeders by birds) and functional (frequency of
      these connections) connectivity? (ii) Are there general patterns of structural
      and functional connectivity across forms? Vegetation cover increased connectivity
      in all three networks, whereas the presence of road gaps negatively affected
      functional but not structural connectivity. Across networks structural
      connectivity was lowest in the summer when birds maintain breeding territories,
      however patterns of functional connectivity appeared to vary with habitat
      fragmentation. Using empirical data this study shows how key urban features and
      season influence movement of feeder-using songbirds, and we provide evidence that
      this is related to greenspace fragmentation.

PMID- 27876883
TI  - Identification of Small Molecule Compounds for Pharmacological Chaperone Therapy
      of Aspartylglucosaminuria.
AB  - Aspartylglucosaminuria (AGU) is a lysosomal storage disorder that is caused by
      genetic deficiency of the enzyme aspartylglucosaminidase (AGA) which is involved
      in glycoprotein degradation. AGU is a progressive disorder that results in severe
      mental retardation in early adulthood. No curative therapy is currently available
      for AGU. We have here characterized the consequences of a novel AGU mutation that
      results in Thr122Lys exchange in AGA, and compared this mutant form to one
      carrying the worldwide most common AGU mutation, AGU-Fin. We show that T122K
      mutated AGA is expressed in normal amounts and localized in lysosomes, but
      exhibits low AGA activity due to impaired processing of the precursor molecule
      into subunits. Coexpression of T122K with wildtype AGA results in processing of
      the precursor into subunits, implicating that the mutation causes a local
      misfolding that prevents the precursor from becoming processed. Similar data were
      obtained for the AGU-Fin mutant polypeptide. We have here also identified small
      chemical compounds that function as chemical or pharmacological chaperones for
      the mutant AGA. Treatment of patient fibroblasts with these compounds results in
      increased AGA activity and processing, implicating that these substances may be
      suitable for chaperone mediated therapy for AGU.

PMID- 27876885
TI  - Generation of a sub-diffraction hollow ring by shaping an azimuthally polarized
      wave.
AB  - The generation of a sub-diffraction optical hollow ring is of great interest in
      various applications, such as optical microscopy, optical tweezers, and
      nanolithography. Azimuthally polarized light is a good candidate for creating an
      optical hollow ring structure. Various of methods have been proposed
      theoretically for generation of sub-wavelength hollow ring by focusing
      azimuthally polarized light, but without experimental demonstrations, especially
      for sub-diffraction focusing. Super-oscillation is a promising approach for
      shaping sub-diffraction optical focusing. In this paper, a planar sub-diffraction
      diffractive lens is proposed, which has an ultra-long focal length of 600 lambda
      and small numerical aperture of 0.64. A sub-diffraction hollow ring is
      experimentally created by shaping an azimuthally polarized wave. The full-width
      at-half-maximum of the hollow ring is 0.61 lambda, which is smaller than the lens
      diffraction limit 0.78 lambda, and the observed largest sidelobe intensity is
      only 10% of the peak intensity.

PMID- 27876886
TI  - Nano sand filter with functionalized nanoparticles embedded in anodic aluminum
      oxide templates.
AB  - Since the ancient Egyptians had used sand as filter media for water purification,
      its principle has been inherited through generations and it is still being used
      now in industries. The sand filter consists of sand literally, and the voids
      within the sand bed are the pores for filtration. Here we present a filtration
      principle using nanoparticles, so that the voids between the nanoparticles can be
      considered as effective pores in nanoscale dimension. Anodic aluminum oxide (AAO)
      membrane has been used as the working template, and the nanoparticles have been
      injected and embedded within the pores of the AAO template. Nanoparticles with
      multiple sizes have been used in order to obtain smaller voids. Moreover, the
      nanoparticles have been functionalized, or electrically charged, with
      arginine/phenylalanine (RF) peptide group. In this way, filtration performance
      for charged particles or molecules, such as methylene blue, has been enhanced.
      Consequently, this study is expected to provide a new principle for fabrication
      of nano voids, or nano pores, and for filtration in nanoscale dimension.

PMID- 27876888
TI  - Bph32, a novel gene encoding an unknown SCR domain-containing protein, confers
      resistance against the brown planthopper in rice.
AB  - An urgent need exists to identify more brown planthopper (Nilaparvata lugens
      Stal, BPH) resistance genes, which will allow the development of rice varieties
      with resistance to BPH to counteract the increased incidence of this pest
      species. Here, using bioinformatics and DNA sequencing approaches, we identified
      a novel BPH resistance gene, LOC_Os06g03240 (MSU LOCUS ID), from the rice variety
      Ptb33 in the interval between the markers RM19291 and RM8072 on the short arm of
      chromosome 6, where a gene for resistance to BPH was mapped by Jirapong Jairin et
      al. and renamed as "Bph32". This gene encodes a unique short consensus repeat
      (SCR) domain protein. Sequence comparison revealed that the Bph32 gene shares
      100% sequence identity with its allele in Oryza latifolia. The transgenic
      introgression of Bph32 into a susceptible rice variety significantly improved
      resistance to BPH. Expression analysis revealed that Bph32 was highly expressed
      in the leaf sheaths, where BPH primarily settles and feeds, at 2 and 24 h after
      BPH infestation, suggesting that Bph32 may inhibit feeding in BPH. Western
      blotting revealed the presence of Pph (Ptb33) and Tph (TN1) proteins using a
      Penta-His antibody, and both proteins were insoluble. This study provides
      information regarding a valuable gene for rice defence against insect pests.

PMID- 27876887
TI  - High Energy Particle Radiation-associated Oncogenic Transformation in Normal
      Mice: Insight into the Connection between Activation of Oncotargets and Oncogene
      Addiction.
AB  - Concerns on high-energy particle radiation-induced tumorigenic transformation of
      normal tissue in astronauts, and in cancer patients undergoing radiotherapy,
      emphasizes the significance of elucidating the mechanisms involved in radiogenic
      transformation processes. Mostly used genetically modified or tumor-prone models
      are less reliable in determining human health risk in space or protracted post
      treatment normal tissue toxicity. Here, in wild type C57BL/6 mice, we related the
      deregulation of distinctive set of tissue-specific oncotargets in major organs
      upon 56Fe (600 MeV/amu; 0.5 Gy/min; 0.8 Gy) particle radiation and compared the
      response with low LET gamma-radiation (137Cs; 0.5 Gy/min; 2 Gy). One of the novel
      findings is the 'tissue-independent' activation of TAL2 upon high-energy
      radiation, and thus qualifies TAL2 as a potential biomarker for particle and
      other qualities of radiation. Heightened expression of TAL2 gene transcript,
      which sustained over four weeks post-irradiation foster the concept of oncogene
      addiction signaling in radiogenic transformation. The positive/negative
      expression of other selected oncotargets that expresses tissue-dependent manner
      indicated their role as a secondary driving force that addresses the diversity of
      tissue-dependent characteristics of tumorigenesis. This study, while reporting
      novel findings on radiogenic transformation of normal tissue when exposed to
      particle radiation, it also provides a platform for further investigation into
      different radiation quality, LET and dose/dose rate effect in healthy organs.

PMID- 27876889
TI  - Harnessing hyperthermostable lactonase from Sulfolobus solfataricus for
      biotechnological applications.
AB  - Extremozymes have gained considerable interest as they could meet industrial
      requirements. Among these, SsoPox is a hyperthermostable enzyme isolated from the
      archaeon Sulfolobus solfataricus. This enzyme is a lactonase catalyzing the
      hydrolysis of acyl-homoserine lactones; these molecules are involved in Gram
      negative bacterial communication referred to as quorum sensing. SsoPox exhibits
      promiscuous phosphotriesterase activity for the degradation of organophosphorous
      chemicals including insecticides and chemical warfare agents. Owing to its bi
      functional catalytic abilities as well as its intrinsic stability, SsoPox is
      appealing for many applications, having potential uses in the agriculture,
      defense, food and health industries. Here we investigate the biotechnological
      properties of the mutant SsoPox-W263I, a variant with increased lactonase and
      phosphotriesterase activities. We tested enzyme resistance against diverse
      process-like and operating conditions such as heat resistance, contact with
      organic solvents, sterilization, storage and immobilization. Bacterial secreted
      materials from both Gram-negative and positive bacteria were harmless on SsoPox
      W263I activity and could reactivate heat-inactivated enzyme. SsoPox showed
      resistance to harsh conditions demonstrating that it is an extremely attractive
      enzyme for many applications. Finally, the potential of SsoPox-W263I to be active
      at subzero temperature is highlighted and discussed in regards to the common idea
      that hyperthermophile enzymes are nearly inactive at low temperatures.

PMID- 27876892
TI  - Handspinning Enabled Highly Concentrated Carbon Nanotubes with Controlled
      Orientation in Nanofibers.
AB  - The novel method, handspinning (HS), was invented by mimicking commonly observed
      methods in our daily lives. The use of HS allows us to fabricate carbon nanotube
      reinforced nanofibers (CNT-reinforced nanofibers) by addressing three significant
      challenges: (i) the difficulty of forming nanofibers at high concentrations of
      CNTs, (ii) aggregation of the CNTs, and (iii) control of the orientation of the
      CNTs. The handspun nanofibers showed better physical properties than fibers
      fabricated by conventional methods, such as electrospinning. Handspun nanofibers
      retain a larger amount of CNTs than electrospun nanofibers, and the CNTs are
      easily aligned uniaxially. We attributed these improvements provided by the HS
      process to simple mechanical stretching force, which allows for orienting the
      nanofillers along with the force direction without agglomeration, leading to
      increased contact area between the CNTs and the polymer matrix, thereby providing
      enhanced interactions. HS is a simple and straightforward method as it does not
      require an electric field, and, hence, any kinds of polymers and solvents can be
      applicable. Furthermore, it is feasible to retain a large amount of various
      nanofillers in the fibers to enhance their physical and chemical properties.
      Therefore, HS provides an effective pathway to create new types of reinforced
      nanofibers with outstanding properties.

PMID- 27876891
TI  - Genetic variations in the PI3K-PTEN-AKT-mTOR pathway are associated with distant
      metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated
      radiation therapy.
AB  - Distant metastasis is the primary failure pattern of nasopharyngeal
      carcinoma(NPC) in intensity-modulated radiation therapy(IMRT) era. This study was
      conducted to find the impact of genetic variations in the phosphatidylinositol 3
      kinase(PI3K)/phosphatase and tensin homologue(PTEN)/v-akt murine thymoma viral
      oncogene homologue(AKT)/mammalian target of rapamycin(mTOR) pathway on the risk
      of distant metastasis in NPC. We genotyped 16 single-nucleotide
      polymorphisms(SNPs) in five core genes in this pathway from 496 patients treated
      by IMRT with or without chemotherapy. The relationships between genetic
      polymorphisms and distant progression were evaluated. We observed that two loci
      in the AKT1 gene(rs3803300 and rs2494738 alone or combined) were associated with
      prognosis, with patients carrying at least one variant allele had significantly
      reduced risk of distant failure, especially in N2-3 group. In addition, we found
      that genetic variation may had some joint effect with N classification in
      recursive-partitioning analysis(RPA) analysis, with which patients were
      stratified into four different risk subgroups (RPA model): RPA1(low risk),
      RPA2(moderate risk), RPA3(high risk) and RPA4(highest risk). Our findings
      suggested that genetic variations within the PI3K signaling pathway modulate the
      development and invasion of NPC patients. Further research is needed to replicate
      the study in other centers and races, and to unravel the functional significance
      of these polymorphisms.

PMID- 27876890
TI  - Why one-size-fits-all vaso-modulatory interventions fail to control glioma
      invasion: in silico insights.
AB  - Gliomas are highly invasive brain tumours characterised by poor prognosis and
      limited response to therapy. There is an ongoing debate on the therapeutic
      potential of vaso-modulatory interventions against glioma invasion. Prominent
      vasculature-targeting therapies involve tumour blood vessel deterioration and
      normalisation. The former aims at tumour infarction and nutrient deprivation
      induced by blood vessel occlusion/collapse. In contrast, the therapeutic
      intention of normalising the abnormal tumour vasculature is to improve the
      efficacy of conventional treatment modalities. Although these strategies have
      shown therapeutic potential, it remains unclear why they both often fail to
      control glioma growth. To shed some light on this issue, we propose a
      mathematical model based on the migration/proliferation dichotomy of glioma cells
      in order to investigate why vaso-modulatory interventions have shown limited
      success in terms of tumour clearance. We found the existence of a critical cell
      proliferation/diffusion ratio that separates glioma responses to vaso-modulatory
      interventions into two distinct regimes. While for tumours, belonging to one
      regime, vascular modulations reduce the front speed and increase the infiltration
      width, for those in the other regime, the invasion speed increases and
      infiltration width decreases. We discuss how these in silico findings can be used
      to guide individualised vaso-modulatory approaches to improve treatment success
      rates.

PMID- 27876893
TI  - Highly Bendable In-Ga-ZnO Thin Film Transistors by Using a Thermally Stable
      Organic Dielectric Layer.
AB  - Flexible In-Ga-ZnO (IGZO) thin film transistor (TFT) on a polyimide substrate is
      produced by employing a thermally stable SA7 organic material as the multi
      functional barrier and dielectric layers. The IGZO channel layer was sputtered at
      Ar:O2 gas flow rate of 100:1 sccm and the fabricated TFT exhibited excellent
      transistor performances with a mobility of 15.67 cm2/Vs, a threshold voltage of
      6.4 V and an on/off current ratio of 4.5 * 105. Further, high mechanical
      stability was achieved by the use of organic/inorganic stacking of dielectric and
      channel layers. Thus, the IGZO transistor endured unprecedented bending strain up
      to 3.33% at a bending radius of 1.5 mm with no significant degradation in
      transistor performances along with a superior reliability up to 1000 cycles.

PMID- 27876894
TI  - DDIT4 regulates mesenchymal stem cell fate by mediating between HIF1alpha and
      mTOR signalling.
AB  - Stem cell fate decisions to remain quiescent, self-renew or differentiate are
      largely governed by the interplay between extracellular signals from the niche
      and the cell intrinsic signal cascades and transcriptional programs. Here we
      demonstrate that DNA Damage Inducible Transcript 4 (DDIT4) acts as a link between
      HIF1alpha and mTOR signalling and regulation of adult stem cell fate. Global gene
      expression analysis of mesenchymal stem cells (MSC) derived from single clones
      and live RNA cell sorting showed a direct correlation between DDIT4 and
      differentiation potentials of MSC. Loss and gain of function analysis
      demonstrated that DDIT4 activity is directly linked to regulation of mTOR
      signalling, expression of pluripotency genes and differentiation. Further we
      demonstrated that DDIT4 exert these effects down-stream to HIF1alpha. Our
      findings provide an insight in regulation of adult stem cells homeostasis by two
      major pathways with opposing functions to coordinate between states of self
      renewal and differentiation.

PMID- 27876895
TI  - Multiple crosstalk between TOR and the cell integrity MAPK signaling pathway in
      fission yeast.
AB  - In eukaryotic cells, the highly conserved Target of Rapamycin (TOR) and the
      Mitogen Activated Protein Kinase (MAPK) signaling pathways elicit adaptive
      responses to extra- and intracellular conditions by regulating essential cellular
      functions. However, the nature of the functional relationships between both
      pathways is not fully understood. In the fission yeast Schizosaccharomyces pombe
      the cell integrity MAPK pathway (CIP) regulates morphogenesis, cell wall
      structure and ionic homeostasis. We show that the Rab GTPase Ryh1, a TORC2
      complex activator, cross-activates the CIP and its core member, the MAPK Pmk1, by
      two distinct mechanisms. The first one involves TORC2 and its downstream
      effector, Akt ortholog Gad8, which together with TORC1 target Psk1 increase
      protein levels of the PKC ortholog Pck2 during cell wall stress or glucose
      starvation. Also, Ryh1 activates Pmk1 in a TORC2-independent fashion by prompting
      plasma membrane trafficking and stabilization of upstream activators of the MAPK
      cascade, including PDK ortholog Ksg1 or Rho1 GEF Rgf1. Besides, stress-activated
      Pmk1 cross-inhibits Ryh1 signaling by decreasing the GTPase activation cycle, and
      this ensures cell growth during alterations in phosphoinositide metabolism. Our
      results reveal a highly intricate cross-regulatory relationship between both
      pathways that warrants adequate cell adaptation and survival in response to
      environmental changes.

PMID- 27876897
TI  - MMPs and TIMPs expression in facial tissue of children with cleft lip and palate.
AB  - BACKGROUND AND AIMS: Morphogenesis of the upper lip and palate is a complex
      process involving highly regulated interactions between epithelial and
      mesenchymal cells. Genetic evidence in humans and mice indicates the involvement
      of matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors
      (TIMPs) in cleft lip palate (CLP) aetiology. This study investigated whether
      expression of MMP-2, MMP-8, MMP-9, TIMP-2, and TIMP-4, which are essential for
      the upper lip and palate fusion, is dysregulated in children with CLP. METHODS:
      Oral mucosa tissue samples were obtained from patients with complete unilateral
      (CU) CLP (n = 25) and complete bilateral (CB) CLP (n = 19) during corrective
      plastic surgery and in unaffected control subjects (n = 10). MMPs and TIMPs
      expression was assessed by immunohistochemistry, and the data were analyzed using
      the Kruskal - Wallis test with the Bonferroni correction. RESULTS: In CLP
      patients, MMP-2, TIMP-2 immunoreactivity in the oral mucosa was seen to have a
      few to abundant structures, but the overall number of MMP-2, TIMP-2-positive
      structures was greater than that in controls (P < 0.01). The total number of TIMP
      4, MMP-9-positive cells showed a significant decrease in the CBCLP compared with
      that of CUCLP (P < 0.001). MMP-8 expression trends in the CLP group were similar
      to those of the control group. CONCLUSIONS: The results suggest that TIMP-4 and
      MMP-9 are the main ECM remodeling regulatory proteins expressed in CUCLP affected
      tissues of the oral mucosa. The increased expression of MMP-2 and TIMP-2 in CLP
      tissues implicates these factors in the regulation of cell migration during ECM
      turnover independently of different types of clefts. Investigation of MMP and
      TIMP expression in tissue samples from patients with CLP appears to be a
      promising approach to the etiopathogenesis of CLP.

PMID- 27876898
TI  - Treatment of brain metastases.
AB  - BACKGROUND: Brain metastases are a very common neurological sequela in cancer
      patients. The ability of current anti-cancer therapies to prolong overall
      survival is beleaguered by this development in the case of a number of different
      cancers. This review provides a general overview of relevant treatment
      modalities, highlights major decision strategies used in selecting the optimal
      treatment algorithm and summarizes important steps necessary before initiating
      therapy. METHODS: A PubMed database search was done to identify publications
      describing the treatment of brain metastases including surgery, radiotherapy and
      symptomatic care. RESULTS AND CONCLUSION: Patient performance status and extent
      of disease play the most important roles in selecting between an aggressive or
      more conservative approach. As several other options are available, treatment
      decisions should be made in cooperation with multiple medical specialties and the
      involvement of multidisciplinary teams. In the future, brain metastases could
      become less of a treatment obstacle than they are today.

PMID- 27876896
TI  - The Reproductive Toxicity of CdSe/ZnS Quantum Dots on the in vivo Ovarian
      Function and in vitro Fertilization.
AB  - Despite the usefulness of quantum dots (QDs) in biomedicine and optoelectronics,
      their toxicity risks remain a major obstacle for clinical usages. Hence, we
      studied the reproductive toxicity of CdSe/ZnS QDs on two aspects, (i) in vivo
      ovarian functions and (ii) in vitro fertilization process. The body weight,
      estrous cycles, biodistribution of QDs, and oocyte maturation are evaluated on
      female mice treated with QDs. The mRNA level of the follicle-stimulating hormone
      receptor (FSHr) and luteinizing hormone receptor (LHr) in ovaries are assayed.
      Then, the matured cumulus-oocyte-complexes are harvested to co-culture with in
      vitro capacitated sperms, and the in vitro fertilization is performed. The result
      revealed that QDs are found in the ovaries, but no changes are detected on the
      behavior and estrous cycle on the female mice. The mRNA downregulations of FSHr
      and LHr are observed and the number of matured oocytes has shown a significant
      decrease when the QDs dosage was above 1.0 pmol/day. Additionally, we found the
      presence of QDs has reduced the in vitro fertilization success rate. This study
      highly suggests that the exposure of CdSe/ZnS QDs to female mice can cause
      adverse effects to the ovary functions and such QDs may have limited applications
      in clinical usage.

PMID- 27876899
TI  - Check list of parasites and bacteria recorded from pangolins (Manis sp.).
AB  - Sound knowledge on parasite fauna of pangolins is crucial for evaluation of their
      health status. In the present review, a checklist of 34 genera of parasites and
      bacteria, including 4 genera of protozoan, 13 genera of helminthes, 8 genera of
      ticks, 2 genera of mites and 7 genera of bacteria reported from pangolins was
      compiled and their zoonotic potential were discussed. The aim of this checklist
      is to underline the information gap and to provide a reference list of parasites
      and bacteria known for pangolins to assist in their further investigation.

PMID- 27876900
TI  - The common zoonotic protozoal diseases causing abortion.
AB  - Toxoplasmosis, neosporosis, sarcosporidiosis (sarcocystosis) and trypanosomiasis
      are the common zoonotic protozoal diseases causing abortion which caused by
      single-celled protozoan parasites; Toxoplasma gondii, Neospora caninum,
      Sarcocystis spp and Trypanosoma evansi, respectively. Toxoplasmosis is generally
      considered the most important disease that causing abortion of both pregnant
      women and different female animals throughout the world, about third of human
      being population had antibodies against T. gondii. The infection can pass via
      placenta, causing encephalitis, chorio-retinitis, mental retardation and loss of
      vision in congenitally-infected children and stillbirth or mummification of the
      aborted fetuses of livestock. Neosporosis is recognized as a major cause of
      serious abortion in varieties of wild and domestic animals around the world
      particularly cattle, the disease cause serious economic losses among dairy and
      beef cattle due to decrease in milk and meat production. While unlike
      toxoplasmosis, neosporosis is not recognized as a human pathogen and evidence to
      date shows that neosporosis is only detected by serology in the human population.
      Sarcosporidiosis also can cause abortion in animals particularly cattle,
      buffaloes and sheep with acute infection through high dose of infection with
      sarcocysts. On the other hand, humans have been reported as final and
      intermediate host for sarcosporidiosis but not represent a serious health
      problem. Trypanosomiasis by T. evansi cause dangerous infection among domestic
      animals in tropical and subtropical areas. Several cases of abortion had been
      recorded in cattle and buffaloes infected with T. evansi while, a single case of
      human infection was reported in India. Trichomoniasis and babesiosis abortion
      occurs with non-zoonotic Trichomonas and Babesia species while the zoonotic
      species had not been incriminated in induction of abortion in both animals and
      man. The current review article concluded that there is still need of wide scope
      for evaluation of the zoonotic impact and control of these diseases.

PMID- 27876901
TI  - Nematodes ultrastructure: complex systems and processes.
AB  - Nematode worms are among the most ubiquitous organisms on earth. They include
      free-living forms as well as parasites of plants, insects, humans and other
      animals. Recently, there has been an explosion of interest in nematode biology,
      including the area of nematode ultrastructure. Nematodes are round with a body
      cavity. They have one way guts with a mouth at one end and an anus at the other.
      They have a pseudocoelom that is lined on one side with mesoderm and on the other
      side with endoderm. It appears that the cuticle is a very complex and
      evolutionarily plastic feature with important functions involving protection,
      body movement and maintaining shape. They only have longitudinal muscles so; they
      seem to thrash back and forth. While nematodes have digestive, reproductive,
      nervous and excretory systems, they do not have discrete circulatory or
      respiratory systems. Nematodes use chemosensory and mechanosensory neurons
      embedded in the cuticle to orient and respond to a wide range of environmental
      stimuli. Adults are made up of roughly 1000 somatic cells and hundreds of those
      cells are typically associated with the reproductive systems. Nematodes
      ultrastructure seeks to provide studies which enable their use as models for
      diverse biological processes including; human diseases, immunity, host-parasitic
      interactions and the expression of phylogenomics. The latter has, however, not
      been brought into a single inclusive entity. Consequently, in the current review
      we tried to provide a comprehensive approach to the current knowledge available
      for nematodes ultrastructures.

PMID- 27876902
TI  - Evaluation of the alum-naloxone adjuvant activity against experimental murine
      leishmaniasis due to L. major.
AB  - Leishmaniasis is caused by intracellular parasites of Leishmania species, which
      are transmitted by the bite of the sandfly. Recovery and protection against the
      infection depends on the induction of a strong Th1 type of immune response.
      Vaccination of mice with the opioid antagonist naloxone can promote the
      activation of the Th1 responses. We studied the efficacy of the mixture of
      naloxone and alum, as an adjuvant, to enhance immune responses and induce
      protection against Leishmania major infection in BALB/c as a susceptible mouse
      model. BALB/c mice were immunized with Ag-naloxone-alum, Ag-alum, Ag-naloxone or
      PBS subcutaneously three times at 2-week intervals. The humoral and cellular
      specific immune responses were assessed 2 weeks after the last immunization and
      compared with the control mice. Our results indicated that the administration of
      alum-naloxone as an adjuvant increased the capability of L. major promastigote
      antigens to enhance lymphocyte proliferation, the levels of IFN-gamma, and the
      IFN-gamma/IL-5 ratio. The results of DTH showed that there were no significant
      differences in footpad swelling between the groups of immunized mice as compared
      with the non-vaccinated control group; however, no significant differences were
      observed in the survival rate among groups. It can be concluded that although
      immunization with the alum-naloxone mixture in combination with the autoclaved L.
      major promastigote antigens could enhance cellular immunity and shift the immune
      response to a Th1 pattern, it could not protect the mice against Leishmania major
      infection.

PMID- 27876903
TI  - Alternations in the liver enzymatic activity of Common carp, Cyprinus carpio in
      response to parasites, Dactylogyrus spp. and Gyrodactylus spp.
AB  - The present study was carried out to investigate the effects of parasites,
      monogenea, Dactylogyrus spp. and Gyrodactylus spp. on some enzymatic and
      biochemical components of liver in healthy and infected common carp, Cyprinus
      carpio. For this purpose, 10 healthy and 10 infected fish were collected from
      farm. The blood samples were taken and after separation of serum, the values of
      Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) enzymes
      activities as well as Creatinine and Urea were measured. Based on obtained
      results, the values of AST, ALT enzymes activities as well as Creatinine and Urea
      were higher in the infected fish compared to non-infected fish. In conclusion;
      our results reveals that infection with external parasites, Dactylogyrus spp. and
      Gyrodactylus spp. can causes some dysfunctions in liver and kidney of common
      carp.

PMID- 27876904
TI  - Effects of storage temperature on survival and infectivity of three indigenous
      entomopathogenic nematodes strains (Steinernematidae and Heterorhabditidae) from
      Meghalaya, India.
AB  - Three locally isolated strains of entomopathogenic nematodes (EPNs), viz.
      Heterorhabditis indica, Steinernema thermophilum and Steinernema glaseri, from
      Meghalaya, India were characterized in terms of storage temperature and survival
      and infectivity of their infective juveniles (IJs). The survival and infectivity
      of nematode IJs was studied at, 5 +/- 2 and 25 +/- 2  degrees C, for a period of
      120 days, using deionized water as storage medium. The viability of nematode IJs
      was checked by mobility criterion at different storage periods, while the
      infectivity of nematode IJs was ascertained on the basis of establishment of IJs,
      using Galleria mellonella larva mortality tests in petridishes. The results of
      this study revealed that storage temperature markedly affects the survival as
      well as the establishment of nematode IJs of the three EPN species. At 5  degrees
      C, comparatively higher rate of IJ's survival (i.e. 74-86 %) was observed for 15
      days of storage, but the same reduced drastically to 28-32 % after 30 days of
      storage for H. indica and S. thermophilum. On the other hand, at 25  degrees C,
      the survival of nematode IJs was observed till 120 days for all the three studied
      EPNs. In case of S. thermophilum and S. glaseri, higher rate of IJs survival (>75
      %) was observed respectively at 15 and 30 days of observation. The study also
      showed that the establishment of IJs of the three EPN species declines with
      increase in storage periods, at both the test temperatures. In general, the
      nematodes stored at 25  degrees C showed comparatively better establishment than
      those stored at 5  degrees C. Among the three EPN studied, the establishment of
      S. glaseri was comparatively better than the rest of the species at both the
      temperatures and for different storage durations. In conclusion, our study adds
      further valuable information about the effect of storage temperature on survival
      and infectivity of three indigenous EPN species of Meghalaya, India which appears
      to be promising biocontrol agents of local insect pests.

PMID- 27876905
TI  - Studies on prevalence of endo-parasitic infection in wild carnivores maintained
      under captive state.
AB  - The present study was conducted to observe the prevalence of endo-parasites in
      wild carnivores maintained under captive state at Tyavarekoppa Tiger and Lion
      Safari unit near to Veterinary College, Shimoga. A total of 54 wild carnivores
      were included in the study and the fresh fecal samples were collected, examined
      on the same day by direct and sedimentation techniques for endo-parasitic
      eggs/ova in the laboratory. Out of 15 tigers samples screened, 12 were harboring
      mixed infections of Strongyle spp., Toxocara spp, oocysts of coccidia and
      Spirometra spp. ova/eggs. Among 21 leopards sample screened, only 11 fecal
      samples showed eggs of Toxocara spp. and three showed eggs/ova of Spirometra spp.
      Of the 12 lion fecal samples examined, only 3 harbored eggs Toxocara spp. and two
      showed mixed infections of Strongyle spp., Toxocara spp, oocysts of coccidia.
      Among six Jackals screened, three faecal samples found positive for Strongyle
      spp. and Toxocara spp. eggs/ova.

PMID- 27876906
TI  - Topical terbinafine in the treatment of cutaneous leishmaniasis: triple blind
      randomized clinical trial.
AB  - Leishmaniasis is a spectrum of disease condition with considerable health
      impacts, caused by different species of Leishmania. This disease is currently
      endemic in 98 countries and territories in the world. There are many treatment
      modalities for cutaneous leishmaniasis. The use of topical terbinafine in the
      treatment of cutaneous leishmaniasis has recently been considered. Eighty-eight
      participants more than two years old with proven acute CL by a positive direct
      smear were randomly allocated to one of the two study arms: first group received
      meglumine antimoniate (Glucantime) 20 mg/kg/day intramuscular injection (IM) plus
      a placebo ointment (Mahan Vaseline) for 20 days. The second group received
      meglumine antimoniate (Glucantime) 20 mg/kg/day IM plus topical terbinafine, for
      20 days and were monitored closely by dermatologist during the course of the
      study. Crude regression analysis showed that there was no significant difference
      between placebo and intervention group regarding partial or complete treatment
      (partial treatment: HRcrude = 1.1, CI 95 % = 0.7-1.7; complete treatment: HRcrude
      = 1.1, CI 95 % = 0.8-1.7). Although, there was no statistically significant
      different between the two treatment groups, but clinically it seems that the
      treatment rate in those who receive glucantime plus terbinafine was more
      effective than the other group. However this rate depended on the type of
      lesions. As data indicated ulcerated nodules, papules and plaque in experimental
      group have been completely improved two times faster than placebo group.
      Ulcerated nodules, nodules and plaque were partially improved faster in those
      used tebinafine than placebo ointment.

PMID- 27876907
TI  - Prevalence of Cryptosporidium spp. in ruminants of Lorestan province, Iran.
AB  - Cryptosporidiosis is one of the important zoonotic diseases caused by an
      intracellular protozoan parasite called Cryptosporidium. This study aimed to
      investigate the prevalence of Cryptosporidium spp. infection on 1,115 ruminants,
      cattle, sheep and goats, in Lorestan province, Iran. Using formol-ether
      concentration technique and modified Ziehl-Neelsen staining method afterwards,
      the overall prevalence of Cryptosporidium spp. infection in ruminants of Lorestan
      province was 7.17 %. Prevalence of infection was 9.07 % (39 of 430), 5.80 % (20
      of 345) and 6.18 % (21 of 340) for cattle, sheep and goats respectively. There
      was no significant difference between contamination of all examined animals and
      different geographical and climatic situations (P > 0.05) and diarrhea was not
      directly associated with Cryptosporidium infection (P > 0.05). In conclusion, the
      prevalence of cryptosporidiosis in Lorestan province was relatively low, but it
      should be noticed that this opportunistic parasite is zoonosis and also can make
      epidemics in ruminants as well as human population in suitable conditions.

PMID- 27876908
TI  - Effect of two hydatid cyst antigens on the growth of melanoma cancer in C57/black
      mice.
AB  - Hydatid cyst is the larval stage of Echinococcus granulosus. In previous studies
      inhibitory effect of this parasite on cancer cell growth in culture medium has
      been shown. In this study effect of hydatid cyst antigens on tumor growth in
      experimental animals has been investigated. Two antigens of hydatid cyst
      including protoscolices excretory secretory antigen and hydatid fluid absorbed on
      alum as adjuvant were injected to two groups of C57/black mice as case groups.
      Control groups were injected with only saline and alum. All mice then were
      injected with melanoma cells. Both antigens reduced the tumor size in mice in
      case groups. The difference of tumor size in mice in case groups and control
      group was statistically significant. In conclusion, anti-tumor effect of hydatid
      cyst antigens may be related to antigenic similarities which exist between
      hydatid cyst and cancer cells.

PMID- 27876909
TI  - Prevalence of gastrointestinal parasites in bovines in and around Junagadh
      (Gujarat).
AB  - Coprological examination of 416 bovine faecal samples revealed the presence of
      parasitic stages of Toxocara vitulorum, strongyles, Strongyloides spp., Fasciola
      spp., amphistomes, coccidia (Eimeria spp. and Cryptosporidium spp.) and
      Buxtonella sulcata. About 42 % (n = 302) faecal samples from cattle and 36 % (n =
      114) samples from buffaloes were positive for gastrointestinal (GI) parasitic
      infections. Both cattle (14.57 %) and buffalo (15.79 %) had the highest incidence
      of Buxtonella sulcata, respectively. The overall incidence of GI parasitic
      infections in young animals (below 1 year) was higher followed by older (more
      than 5 years) and adult animals (1-5 years) and the difference was statistically
      significant (p < 0.05). Non descriptive breeds of bovines showed more parasitic
      infections than pure breeds, the difference being statistically non-significant
      (p > 0.05). Season wise GI parasitic infections were recorded to be non
      significantly (p > 0.05) higher in monsoon (48.38 %) followed by summer (39 %)
      and winter (34.61 %) in cattle. There was no significant variation of GI
      infections in buffaloes in relation to season though highest prevalence was
      documented in monsoon (44.89 %) followed by winter (35.71 %) and summer (24.32
      %). Similarly, sex wise females recorded higher infection rates than males in
      bovines and the difference being statistically non-significant (p > 0.05).

PMID- 27876910
TI  - Low sensitivity of the ImmunocardSTAT(r) Crypto/Giardia Rapid Assay test for the
      detection of Giardia and Cryptosporidium in fecal samples from children living in
      Libreville, Central Africa.
AB  - Giardiasis and cryptosporidiosis are now recognized as neglected tropical
      parasitic diseases. The risk of their dissemination  in developing countries,
      such as Gabon, is increasing, due to urban crowding and poor sanitation.
      Accurate, simple and rapid diagnosis tools are thus necessary for the estimation
      of their real burden. The aim of this study was to evaluate the performances of
      the ImmunocardSTAT(r)Crypto/Giardia Rapid Assay test for the detection of
      Cryptosporidium (C.) spp. and Giardia (G.) duodenalis in children living in
      Libreville, Gabon. Stool samples of 173 healthy children were screened by routine
      microscopic using the merthiolate iodine formol concentration technique for
      Giardia, the modified Ziehl Neelsen (ZN) staining for Cryptosporidium and the
      ImmunocardSTAT(r) Crypto/Giardia RDT for the detection of Giardia and
      Cryptosporidium parasite forms and antigens respectively. G. duodenalis was
      detected with microscopy and the ImmunocardSTAT(r) Crypto/Giardia in 27 (15.6 %)
      and 22 (13.3 %) fecal samples respectively. C. spp. oocysts were found in 18
      (10.4 %) ones, whereas only one sample was positive with the
      immunochromatographic assay. When microscopic examination was considered as the
      reference method, sensitivity and specificity of the ImmunocardSTAT(r)
      Crypto/Giardia Rapid Assay were found to be 63.0 %, 96.6 and 5.5 %, 99.3 % for G.
      duodenalis and C. spp. respectively. The prevalence of G. duodenalis and C. spp.
      carriage is high in children from Libreville. A low sensitivity of the
      ImmunocardSTAT(r) Crypto/Giardia for the detection of both parasites is observed.
      It is thus inappropriate as a diagnostic tool for detecting asymptomatic
      carriers.

PMID- 27876911
TI  - Detection of Theileria annulata carriers in Holstein-Friesian (Bos taurus taurus)
      and Sistani (Bos taurus indicus) cattle breeds by polymerase chain reaction in
      Sistan region, Iran.
AB  - Theileria annulata is common in tropical and subtropical regions especially in
      Iran and causes great economic losses in cattle industry. In Iran the
      epidemiological aspects of bovine theileriosis in different breeds of cattle is
      poorly understood. The aim of present study is comparison of the number of T.
      annulata carriers in the two major cattle breeds (Holstein-Friesian and Sistani)
      in Sistan of Iran by giemsa and polymerase chain reaction (PCR) methods. During
      winter 2013, 160 native cattle, from the two major breeds in Sistan, with the
      mean age of more than one year and without typical clinical symptoms of
      theileriosis were selected. At first, a thin layer smear was held from their ear
      sublime vein blood for Giemsa staining method. In order to do PCR assay, jugular
      vein blood sample of each cow was taken. The PCR employs primers specific for the
      721-bp gene fragment encoding the 30-kDa major merozoite surface antigen of T.
      annulata. By PCR method, 38 (47.5 %) Holstein blood samples and 22 (27.5 %)
      Sistani blood samples had DNA of T. annulata and considered positive (The
      correlation was significant at values of P < 0.05). By checking 160 blood smears
      with light microscope and lens * 100, only 10 samples (6.25 %) were positive for
      T. annulata. Statistical comparison between PCR and smear method showed that the
      PCR method is more sensitive and accurate in comparison to Giemsa staining method
      to diagnose the asymptomatic carriers of T. annulata.

PMID- 27876912
TI  - Synbiotic (Biomin imbo) alters gut bacterial microflora of Russian sturgeon,
      Acipenser guldenstadti (Brandt & Ratzeburg, 1833) in a time-dependent pattern.
AB  - We investigated the efficiency of Synbiotic (Biomin imbo) in alternation and
      stabilization of gut microflora of Russian sturgeon, Acipenser guldenstadti. For
      this purpose, five experimental treatments and one control group with three
      replicates were considered. In treatment groups, fish were fed with diet
      containing 1 (T1), 1.5 (T2), 2 (T3), 2.5 (T4) and 3 (T5) g Synbiotic/kg diet. In
      control group, fish were fed without supplement of Synbiotic. Sampling for
      bacterial studies was conducted at days 20, 40 and 60 after the beginning of the
      experiment. According to results, there were no significant differences in total
      bacterial count between Synbiotic treatments and also in comparison with control
      group 20 days after the beginning of the experiment (P > 0.05). At days 40 and 60
      of experiment, the highest total bacterial counts were observed in control and T1
      group respectively. At day 20, the lactic acid bacteria count was higher
      significantly in Synbiotic treatments compared to control group (P < 0.05). In
      all sampling times (i.e. days 20, 40 and 60), the highest lactic acid bacteria
      count was observed in fish fed with 3 g Synbiotic/kg diet i.e. treatment 5 (P <
      0.05). In each experimental group, total bacteria and lactic acid bacteria counts
      increased significantly as the duration of experiment expanded. In this regard,
      these parameters were significantly higher at day 60 compared to day 40 and 20 (P
      < 0.05). In conclusion, our results showed that Synbiotic (Biomin imbo) alters
      and stabilizes efficiently the microflora of Russian sturgeon gut towards lactic
      acid bacteria in a time-dependent pattern.

PMID- 27876913
TI  - Circulating cathodic antigen cassette test versus haematuria strip test in
      diagnosis of urinary schistosomiasis.
AB  - Urinary schistosomiasis caused by Schistosoma haematobium constitutes a major
      public health problem in many tropical and sub-tropical countries. This study was
      conducted to evaluate circulating cathodic antigen cassette test and haematuria
      strip test for detection of S. haematobium in urine samples and to evaluate their
      screening performance among the study population. Microscopy was used as a gold
      standard. A total of 600 urine samples were examined by microscopy for detection
      of S. haematobium eggs, screened for microhaematuria using Self-Stik reagent
      strips and screened for circulating cathodic antigen (CCA) using the urine-CCA
      cassette test. The specificity of CCA, microhaematuria and macrohaematuria was
      96.4, 40.6 and 31.2 % respectively while the sensitivity was 88.2, 99.3 and 100 %
      respectively which was statistically significant (P < 0.001). These findings
      suggest that using of urine-CCA cassette test in diagnosis of urinary
      schistosomiasis is highly specific (96.4 %) compared with the highly sensitive
      haematuria strip test (100 %). The degree of agreement between microscopic
      examination and CCA detection was 99.3 % with highly statistically significant
      difference (P < 0.001). The combination of two techniques could potentially use
      for screening and mapping of S. haematobium infection.

PMID- 27876914
TI  - Ultrastructural studies on Setaria digitata by scaning electron microscopy.
AB  - Ultrastructural details of adult male and female worms of Setaria species
      collected from the peritoneal cavities of bovines slaughtered in and around
      Hyderabad, Telangana, India were studied using scanning electron microscopy. The
      worms exhibited peribuccal crown with round mouth opening encircled by a pair of
      lateral appendages and slightly notched dorso and ventro projections at the
      anterior end where as bosses and fine cuticular striations were seen all over the
      body. Posterior end of female worm ended in a round knob with a pair of lateral
      appendages whereas three pairs of precloacal, a pair of adcloacal, three pairs of
      postcloacal papillae, a central papillae just in front of the cloaca, a single
      tongue shaped spicule emerging from the cloaca, and a phasmid in front of a pair
      of lateral appendages were seen at the posterior end of male worm. The
      ultrastructural details confirmed the worms as Seteria digitata.

PMID- 27876915
TI  - Effect of olive leaf, Satureja khuzestanica, and Allium sativum extracts on
      Giardia lamblia cysts compared with metronidazole in vitro.
AB  - Giardia lamblia is one of the common causes of worldwide diarrhea in children.
      Appropriate medicinal treatment for giardiasis is available but there are some
      evidences of drug resistance, insufficient efficacy, and unpleasant side effects.
      In order to reach a more natural drug with suitable efficacy and the lowest side
      effects, the effects of the hydroalcoholic extracts of olive leaf, Satureja
      khuzestanica, and Allium sativum on G. lamblia cysts were evaluated in vitro, as
      well as antigiardial effect of the extracts was compared with metronidazole as
      the drug of choice. 2 and 5 mg of the plants extracts and powder of metronidazole
      250 mg pills were added to 1 ml of G. lamblia cysts suspension (containing 5,000
      cyst/ml normal saline), and the percentages of bioavailability of G. lamblia
      cysts were examined at the 2nd and 4th h after exposure and in 4 and 37  degrees
      C temperatures using eosin 0.1 % and a haemocytometer. The data were analyzed by
      multiway ANOVA test, Tukey's test, and the SPSS software, version 18. The
      examinations demonstrated that olive leaf extract had the most fatality rate on
      G. lamblia cysts in vitro (37.90 +/- 7.01 %), followed by the extract of S.
      khuzestanica (32.52 +/- 9.07 %). Metronidazole 250 mg pills had relatively
      effective fatality rate on G. lamblia cysts in vitro (28.75 +/- 10.30 %), whereas
      A. sativum (garlic) had the lowest fatality effect on G. lamblia cysts in vitro
      (22.65 +/- 10.47 %). With respect to higher fatality effect of olive leaf and S.
      khuzestanica extracts compared with metronidazole in vitro, these plants can be
      used as suitable candidates to make new antigiardial drugs with low side effects
      and without drug resistance in the treatment of giardiasis in children.

PMID- 27876916
TI  - A survey on the prevalence of strongyles species in working donkeys in North-West
      of Iran.
AB  - Faecal samples for detection of gastrointestinal parasites were collected from 60
      donkeys from 6 villages in Marand, North-West of Iran. Faecal samples of 2
      donkeys (3.33 %) were negative for parasite eggs. 48 positive donkeys (81.66 %)
      were infected with a single parasite type, 9 (15.51 %) and 1 (1.66 %) of donkeys
      had multiple infections with two and three parasites, respectively. The highest
      prevalence and intensity rate belonged to small strongyles. The overall
      prevalence of intestinal parasites eggs in the positive donkeys were: strongyles
      100 %, Parascaris equorum (15.51 %), Habronema spp. 1.72 %. Larval identification
      showed that small strongyle larvae were most frequent (100 %) followed by
      Strongylus edentatus (5.17 %), S. equinus (35.71 %) and S. vulgaris (26.66 %).
      This study revealed that donkeys in Iran are infected with a range of helminths,
      which are representatives of the important pathogenic parasites found in equids
      worldwide.

PMID- 27876917
TI  - Treatment and control of Trixacarus caviae infestation in a conventional guinea
      pig (Cavia porcellus) breeding colony.
AB  - A case of sarcoptic mange caused by Trixacarus caviae in a conventional guinea
      pig breeding colony is reported. The infestation was reported in a large colony
      of guinea pigs during the month of July, 2013 affecting 30 breeder guinea pigs.
      Severely infested animals were treated individually with subcutaneous injection
      of ivermectin 1 % w/v (Neomec(r)) at the rate of 400 ug/kg body weight 10 days
      apart. Three doses of ivermectin were sufficient to eliminate the parasite which
      tested negative after 30 days of the first treatment. The entire colony was given
      preventive dose of ivermectin spray (2 mg/ml solution) following the same
      schedule. Strict hygienic measures were followed. New hair growth in the severely
      affected animals was evidenced on 30th day of treatment.

PMID- 27876918
TI  - Report of Amblyomma testudinarium in mithuns (Bos frontalis) from eastern Mizoram
      (India).
AB  - Physical examination of semi-domesticated, free ranging mithuns (Bos frontalis)
      during an animal health check-up and treatment camp organized at Khuwangleng
      village in the Champhai district of Mizoram, India and adjacent to Myanmar Border
      revealed presence of unusually large blood engorged ticks attaching to the dewlap
      and inner aspects of thighs. On the basis of morphological study, the ticks were
      found indistinguishable from female Amblyomma testudinarium. Prevalence rate of
      the tick species in mithuns living in the forests was 9.09 % which was recorded
      as the highest of all reports made earlier from the North Eastern region of
      India. Medical and veterinary significance of the tick is discussed in the light
      of available literature.

PMID- 27876919
TI  - Oestrus ovis larvae in nasal cavity of sheep: a case report.
AB  - The present communication reports the infestation of nasal cavities of sheep by
      larvae of Oestrus ovis from Kashmir Valley.

PMID- 27876920
TI  - Use of chicken embryonated eggs for evaluating the virulence of Toxoplasma
      gondii.
AB  - The objective of the present study was to examine the virulence of Toxoplasma
      gondii RH strain tachyzoites in embryonated eggs after continuous passage in Vero
      cell line. The first T. gondii tachyzoites was considered low passage (no
      passage) and then passaged for 80 times on Vero as high passage. Groups of 9-day
      old embryonated eggs with ten eggs in each group were inoculated with 102,103 and
      104 of low or high-passage T. gondii tachyzoites, and any mortality was recorded.
      Suitable samples from different tissues (liver, heart, and brain) of the dead
      embryos were collected for histopathological study. In this study, the mortality
      in group 103 and 104 was observed, but there was no significant differences in
      mortality rate in T. gondii low passage and high passage. This finding exactly
      correspond to previous studies that were performed in mice as animal model for T.
      gondii RH strain. Thus on base of this study we could introduce the embryonated
      eggs as an appropriate animal model to evaluate the virulence of T. gondii
      tachyzoites.

PMID- 27876921
TI  - Ectoparasite (louse, mite and tick) infestations on female turkeys (Galliformes,
      Phasianidae. Meleagris gallopavo) in Iran.
AB  - Wild turkeys (Meleagris gallopavo) were evaluated as potential hosts of
      ectoparasites. Different lice, ticks and mites can infest turkeys and cause
      direct and/or indirect harms and in some cases can also be fatal. Samples
      (feathers) were collected from lateral parts of 15 and 7 female turkeys' body of
      two different turkey flocks, in Rasht, Gilan province and Piranshahr, Western
      Azerbaijan province, Iran, respectively. Feathers were inspected for
      ectoparasites, the collected ectoparasites were decolorized and mounted then
      identified by identification keys in parasitology laboratory. In this research,
      four new lice, one mite and one tick on 13 infested turkeys were identified and
      discussed.

PMID- 27876922
TI  - Anthelmintic potential of Calotropis procera, Azadirachta indica and Punica
      granatum against Gastrothylax indicus.
AB  - Anthelmintic activity of both ethanolic and aqueous extracts of Calotropis
      procera flowers, Azadirachta indica leaves and Punica granatum fruit peel in
      comparison with albendazole was evaluated through in vitro studies by the worm
      motility inhibition assay. Significant anthelmintic effects (p < 0.0005) were
      observed on live Gastrothylax indicus worm as evident from their mortality at 4 h
      post exposure to both ethanolic and aqueous extracts. Phytochemical analysis of
      extracts revealed the presence of phenols, alkaloids, saponins, tannins,
      flavonoids, steroids and triterpenoids. LC-50 values were determined to be 12.05
      mg/ml +/- 3.24 and 23.52 mg/ml +/- 6.4 for C. procera, 24.37 mg/ml +/- 4.11 and
      21.02 mg/ml +/- 4.6 for A. indica, 18.92 mg/ml +/- 4.54 and 24.43 mg/ml +/- 6.96
      for P. granatum ethanolic and aqueous extracts respectively, whereas it was 29.23
      MUg/ml +/- 4.51 for albendazole. The mean mortality index (MI) was 1.0 and 0.90
      for C. procera, 0.90 for A. indica and 0.73 and 0.80 for P. granatum ethanolic
      and aqueous extracts respectively whereas for albendazole it was 1.0. Percent
      mean worm motility inhibition (%WMI) was observed to be between 70 and 100 % for
      different extracts.Various concentrations (5-5000 MUg/ml) of all the plant
      extracts and albendazole were used to detect their cytotoxic effects against HeLa
      cell line to determine CC-50 by MTT assay. CC-50 values, of all the plant
      extracts were determined to be >1000 MUg/ml and for albendazole it was found to
      be >10 MUM. All the three plants can be potential sources for novel
      anthelmintics.

PMID- 27876923
TI  - Escalations in the incidence of canine babesiosis over a period of 8 years (2006
      2013) in Chennai, Tamil Nadu, India.
AB  - Epidemiological studies on the incidence and prevalence of disease will help in
      the monitoring and surveillance of diseases thus preventing occurrence of an
      epidemic. This study focuses on the variations in the incidences of canine
      babesiosis over a period of 8 years in Chennai. Variations have been noticed to
      in the incidence of the species of Babesia affecting dogs. There has been an
      escalation in the incidence of B.gibsoni infection during the study period. The
      factors such as seasonal, age, sex and breed influences on the incidence have
      been studied.

PMID- 27876924
TI  - First report of Oriental latrine flies causing vaginal myiasis in human.
AB  - The present paper reports a case of human vaginal myiasis in a 22 year old woman.
      This is the first report of this fly species to cause vaginal myiasis in human
      till now. The infested maggots were removed from the vagina and cultured in
      laboratory. Entomological studies on the emerged flies showed that the infested
      larvae were Oriental latrine fly Chrysomya megacephala Fabricius. Clinical
      presentation and treatment strategies are discussed also.

PMID- 27876925
TI  - Therapeutic effect of Arctium lappa in Schistosoma haematobium associated kidney
      disturbance: biochemical and molecular effects.
AB  - Schistosoma haematobium (S. haematobium) infection has been found to be strongly
      associated with bladder cancer, which necessitates for discover of a natural new
      therapeutic agent. The aim of this study was to evaluate the therapeutic effect
      of Arctium lappa seed extract in S. haematobium associated kidney disturbance.
      Forty male albino mice were used and divided into four equal groups; group 1
      control includes non-infected healthy mice, groups 2, 3 and 4 subcutaneous
      infected with S. haematobium cercariae. Groups 3 co-treated daily with oral dose
      of A. lappa seed extract (300 mg/kg, bwt) for 15 days in the same time of S.
      haematobium infection. Groups 4 post-treated daily for 15 days with oral dose of
      A. lappa seed extract (300 mg/kg, bwt) after 15 days of S. haematobium infection.
      The results obtained revealed that S. haematobium significantly decreased kidney
      weight and serum sodium, potassium and chloride, but increased urinary volume,
      urinary excretion of sodium, potassium and chloride, serum urea, creatinine and
      uric acid. Schistosoma haematobium also significantly decreased kidney superoxide
      dismutase, glutathione peroxidase and reduced glutathione levels while increased
      kidney lipid peroxidation level. Co- and post-treatment with A. lappa seed
      extract restore all the above parameters to approach the normal values. These
      results were supported with histopathological examinations. In conclusion, A.
      lappa seed extract has therapeutic effect in kidney disturbance caused by S.
      haematobium where co-treatment of A. lappa seed extract was more effective than
      post-treatment of the extract.

PMID- 27876927
TI  - Anticestodal properties of Hibiscus rosa-sinensis L. (Malvaceae): an in vitro and
      in vivo study against Hymenolepis diminuta (Rudolphi, 1819), a zoonotic tapeworm.
AB  - The aim of this study was to investigate the in vitro and in vivo anticestodal
      effects of methanol extract of Hibiscus rosa-sinensis L. (Malvaceae) leaf against
      Hymenolepis diminuta (Rudolphi, 1819), a zoonotic tapeworm. Under the in vitro
      study, H. diminuta worms were exposed to 10, 20 and 40 mg/ml concentrations of
      methanol leaf extract and the effects were judged on the basis of physical
      motility/mortality of worms. On the other hand, in the case of in vivo study, H.
      diminuta infected rats were treated individually with 200, 400 and 800 mg/kg
      doses of leaf extract for 5 days. The effects were judged on the basis of
      reduction in eggs per gram (EPG) of faeces and worm counts. In case of in vitro
      test, the treatment with 40 mg/ml concentration of extract revealed prominent
      anticestodal effect and caused paralysis of worms in 3.00 +/- 0.53 h and
      mortality in 4.08 +/- 0.21 h. However, under in vivo study, the 800 mg/kg dose of
      extract revealed the highest anticestodal effect and caused 66.55 % reduction in
      EPG count and 75.00 % reduction in worm count in the treated animals. The results
      of this study indicated that H. rosa-sinesis leaf extract possesses concentration
      dependent anticestodal effect against H. diminuta, indicating that the plant
      possesses promising active principle for the control of intestinal helminthic
      infections.

PMID- 27876926
TI  - A survey study on gastrointestinal parasites of stray cats in Azarshahr, (East
      Azerbaijan province, Iran).
AB  - Gastrointestinal parasites are among the most common parasitic infections found
      in stray cats, which might act potential helminthic parasites to domestic cats.
      The objective of this study was to determine the prevalence of gastrointestinal
      parasites in stray cats in the city of Azarshahr, which is located in East
      Azerbaijan province, Iran. A cross-sectional study was conducted on 50 necropsied
      stray cats, trapped and collected from different geographic regions of Azarshahr.
      From a total 50 stray cats examined, 15 (30 %) were female and 35 (70 %) were
      male. Overall 47 cats (94 %) were identified as infected with at least one of the
      endoparasites. The prevalence of parasites found were: Taenia taeniaeformis (60
      %), Dipylidium caninum (58 %), Taenia hydatigera (24 %), Mesocestoides lineatus
      (78 %), Ancylostoma tubaeforme (14 %), Toxascaris leonina (30 %), Toxocara cati
      (78 %), Physaloptera praeputialis (10 %), and Syphacia obvelata (10 %).
      Contamination rate for zoonotic parasites of cat was greater than expected in
      AzarShahr region. Therefore, appropriate control measures should be taken and
      preventive methods should be applied.

PMID- 27876928
TI  - In silico sequence analysis, homology modeling and function annotation of
      leishmanolysin from Leishmania donovani.
AB  - Leishmaniases are a complex of diseases that range from the deadly visceral
      disease and some self-curing lesions to gross disfigurations. About 12 million
      peoples from 88 different countries get infected by this protozoan parasite
      through the sand flies. Visceral leishmaniasis is a potentially fatal disease
      endemic to large parts of Asia and Africa, primarily caused by the protozoan
      parasite Leishmania donovani. L. donovani is a species of Leishmania, a
      hemoflagellate parasite and causative agent of visceral leishmaniasis.
      Leishmanolysin is the major surface protein of the parasitic Leishmania.
      Leishmanolysin has been described as a parasite virulence factor and is involved
      in the direct interaction of promastigotes and host macrophage receptors and
      interaction with the complement cascade. In the current study we predicted the 3D
      structure of leishmanolysin using homology modeling as 3D structure prediction
      approach. Leishmanolysin is a stable extracellular stable protein of 561 amino
      acid residues. 3D structure of the leishmanolysin was determined using Protein
      Structure Prediction Server (PS2 Server) selecting MODELLER as 3D structure
      prediction method. Quality analysis of the model through its Ramchandran Plot and
      ERRAT value (94.25) indicated that it is a reliable model. Functional annotation
      showed that this protein is a member of the superfamily cl18220. The information
      thus discussed provides insight to the molecular understanding of structure and
      function of leishmanolysin from L. donovani. The predicted 3-D model may be
      further used in characterizing the protein in wet laboratory.

PMID- 27876929
TI  - Branchial cymothoids infesting the marine food fishes of Malabar coast.
AB  - Occurrence of cymothoid isopods parasitizing the branchial chamber of marine food
      fishes along the Malabar coast was investigated. Live and fresh fishes collected
      from the Ayyikkara fish landing center (Lat. 11 degrees 51'N, Long. 75 degrees
      22'E; Malabar coast, India) were subjected to the thorough observation for the
      presence of branchial cymothoids for 3 consecutive years (November 2009-November
      2012). Among the recovered cymothoids, 11 species were branchial residents
      belonging to 6 genera; the species include Agarna malayi, Catoessa gruneri, C.
      boscii, Joryma hilsae, J. brachysoma, J. engraulidis, J. sawayah, Mothocya
      collettei, M. renardi, Norileca indica and Ryukyua circularis; highest prevalence
      being exhibited by two species of Mothocya, (M. renardi and M. collettei)
      parasitizing the belonidaen fishes, Strongylura leiura (92.15 %) and Tylosurus
      crocodilus crocodilus (87.2 %) respectively. Except Mothocya species, which
      preferred the branchial floor for infestation, all recovered branchial cymothoids
      were found attached the inner wall of the operculum. In several instances, the
      parasites appeared in male-female pairs, one in each branchial cavity. Ovigerous
      female members of all species of branchial cymothoids except R. circularis showed
      remarkable bending either towards left or right depending on whether they are
      located in right or left branchial cavity of their respective host fishes. The
      deleterious effects of parasitization by all recovered branchial cymothoids
      include the formation of a pit like depression in the branchial chamber and
      atrophy of the gill filament; the damage was more pronounced in the gill cavity
      of parasitized host fishes where the ovigerous female member was accommodated.

PMID- 27876930
TI  - Seroprevalence of Toxoplasma gondii infection in domestic dogs in an area from
      northwest of Iran: a cross-sectional study using immunodominant surface antigen 1
      (SAG1).
AB  - Toxoplasma gondii is an obligate intracellular protozoan parasite that infects
      humans and animals. T. gondii surface antigen 1 (SAG1) is an appropriate antigen
      with high specificity and sensitivity for the detection of T. gondii infection in
      humans and animal hosts. The aim of this study was to determine the
      seroprevalence of T. gondii infection using SAG1 antigen (P30) in ownership dogs
      in Meshkin-Shahr district in the northwestern Iran. The sera samples were
      collected from 171 domestic dogs and tested using indirect ELISA (SAG1 antigen).
      The data were analyzed using SPSS software version 13. From a total of 171 dogs,
      82 (48 %) of them were sero-positive. No statistical significant difference was
      seen between T. gondii infection and gender (P = 0.995). The highest sero
      prevalence of rate was observed in >5 years animals; but no statistical
      significant difference was seen between T. gondii infection and age (P = 0.589).
      Our findings indicate that Toxoplasma seropositivity rate is high in ownership
      dogs in northwest of Iran. This is probably due to high exposure to contaminated
      food, soil, or water sources with sporulated Toxoplasma oocysts.

PMID- 27876931
TI  - The prevalence of non-indigenous parasitic copepod (Neoergasilus japonicus)
      spreads with fishes of pet trade in Kerman, Iran.
AB  - Ergasilids are copepods living in the river mouth of freshwaters and parasitic on
      Teleost fish family in both natural and artificial environments. So far, 5
      species of the copepod have been discovered that belong to the genus
      Neoergasilus. This copepod is most likely to be disseminated through aquarium
      trades, aquaculture and over-nutrition, or construction of sand carrying water.
      The females of Ergasilidae are external parasites attaching to the anal and
      dorsal fins and sometimes to gills and nasal cavities of fish living in
      freshwaters. In total, 552 pieces of ornamental fish (301 males and 251 females)
      with length of 5-10 cm from fish (Poecilia sphenops) species (Singapore, Sandy,
      Dirigible and scorpion's tail) were collected from ornamental fish stores in
      different regions of Kerman, Iran during 1 year in 2012-2013 and tested in order
      to examine Neoergasilus japonicus infestation. From 188 adult females
      Neoergasilus japonicus specimens recorded on the fish host, 8 (4.26 %) were on
      the anal, 120 (63.83 %) on the dorsal, 10 (5.32 %), on the pectoral, 45 (23.94 %)
      on the pelvic, and 5 (2.66 %) on the caudal fins. In this study, the prevalence
      of parasitic copepod infestation from Dec. to May was 26.31, 27.69, 26.19, 14,
      18.75, and 7.5 %, respectively. There was no significant difference between
      infestation prevalence in indigenous and non-native fishes (P = 0.18). There were
      significant differences between different months of year in the prevalence and
      intensity of Neoergasilus japonicas (P < 0.05). There was significant difference
      between frequency distribution of Neoergasilus Japonicus infestation in different
      organs (P < 0.05). The male fish infestation (16.3 %) was significantly higher
      than female fish infestation (5.6 %) (P < 0.05). Considering that the
      Neoergasilus japonicus was first observed in native and nonnative ornamental fish
      in Kerman, further studies should be conducted on the copepod infestation in
      stores supplying ornamental fish in other parts of Iran to make more accurate
      judgments.

PMID- 27876932
TI  - Zataria multiflora Bioss: lethal effects of methanolic extract against
      protoscoleces of Echinococcus granulosus.
AB  - The present study was aimed to evaluate the lethal effects of Zataria multiflora
      Boiss (Lamiaceae) methanolic extract against Echinococcus granulosus
      protoscoleces. Protoscoleces were aseptically aspirated from sheep livers having
      hydatid cysts. Various concentrations of the essential oil (2.5-20 mg/mL) were
      used for 10-60 min. Viability of protoscoleces was confirmed using eosin
      exclusion test (0.1 % eosin staining). Obtained results showed that Z. multiflora
      extract at the concentration of 20 mg/mL after 10 min of exposure killed 100 %
      protoscoleces. The mean of mortality rate of protoscoleces after 20 min of
      exposure to the concentration of 10 mg/mL was also 100 %. Lower concentrations of
      Z. multiflora extract provoked a delayed protoscolicidal activity. The findings
      indicated potential of Z. multiflora methanolic extract as a natural source for
      the producing of new scolicidal agent for use in hydatid cyst surgery.

PMID- 27876933
TI  - New potential host for Ryukyua globosa (Crustacea, Isopoda, Cymothoidae) from
      Parangipettai, Southeast coast of India.
AB  - In the present study Ryukyua globosa parasitic isopod on the marine fishes of the
      Parangipettai coast are reported. R. globosa was found attached in the gill
      chamber of Sardinella gibbosa. The attachment position of Ryukyua species differs
      from that of other member of this genus. Until now, R. globosa was only reported
      on Amblygaster sirm and A.leiogaster. S.gibbosa is a new host record for
      R.globosa. R. globosa, branchial parasites, already known from Japan and is now
      recorded from the Southeast coast of India.

PMID- 27876934
TI  - Diversity of parasites in Curimata incompta (Curimatidae), a host from Amazon
      river system in Brazil.
AB  - This paper is the first study on host-parasite relationship in wild Curimata
      incompta Vari, 1984 (Curimatidae) from Amazon river system, Northern Brazil. In
      40 specimens examined from December 2012 to November 2013, 615,818 parasites were
      collected, such as Ichthyophthirius multifiliis, Piscinoodinium pilullare,
      Urocleidoides sp., Posthodiplostomum sp., Gorytocephalus elongorchis and Braga
      patagonica. The parasites' component community had a low Brillouin diversity
      (0.16 +/- 0.15), a low species richness (3.1 +/- 0.7), a low evenness (0.09 +/-
      0.09) and a high dominance of Berger-Parker (0.96 +/- 0.06). I. multifiliis was
      the dominant parasite species and it showed the highest prevalence and intensity
      in the host population. There was an aggregate dispersion of parasites, but the
      low parasitism did not affect the body condition of the host. The occurrence of
      parasites in C. incompta was due to their life habits and food behavior. This
      study, besides expanding the geographical distribution of G. elongorchis in
      Brazil, records the first occurrence of these six parasites in C. incompta.

PMID- 27876935
TI  - Occurrence, morphology and molecular characterisation of Bopyrid parasite
      Epipenaeon ingens Nobili, 1906 (Isopoda: Bopyridae).
AB  - Epipenaeon ingens occurs most commonly in Southeast Coast of India parasitized
      the penaeid shrimp. The present study provides the prevalence, morphological and
      molecular characterisation of E. ingens collected from the host Metapenaeopsis
      stridulans. In the present study highlights the significance of high prevalence
      and genetic diversity of E. ingens in M. stridulans. Intra specific analysis also
      revealed that E. ingens species detected in the present study can be easily
      distinguished from the other genospecies of bopyrids. Further application of this
      molecular tool to investigate the genetic variability among bopyrids detected in
      different hosts may facilitate our understanding of the significance of genetic
      diversity in relation to the infestation of bopyrid species in south coast of
      India.

PMID- 27876936
TI  - In vitro and in vivo anthelmintic activity of seed extract of Coriandrum sativum
      compared to Niclosamid against Hymenolepis nana infection.
AB  - Phytotherapy can be an alternative for the control of gastrointestinal parasites
      in human and animals. Coriander (Coriandrum sativum L.) is a medicinal plant
      which grown as a spice crop all over the world. The seeds of this plant have been
      used to treat parasitic disease, indigestion, diabetes, rheumatism and pain in
      the joints. This study was carried out to compare the efficacy of Niclosamid and
      alcoholic seed extract of C. sativum on Hymenolepis nana infection, in vivo and
      vitro. For in vivo study, Balb/c mice were used, to compare the efficacy of 50
      mg/kg body weight (B.W) of Niclosamid with different doses of alcoholic extracts
      of C. sativum (250, 500, and 750 mg/kg B.W). It was found that the efficacy of
      Niclosamid had reached 100 % after 11 days post treatment, while the efficacy of
      500 and 750 mg/kg B.W of C. sativum reached to 100 % after 15 days after
      treatment. For in vitro study, special nutrient broth media was used. It was
      found that the addition of 1000 mg/ml of Niclosamid had paralyzed and killed
      worms within 5 min, while C. sativum killed them within 30 min. Our results
      showed that extract of C. sativum has good effect against H. nana and could be
      use in traditional medicine for treatment of parasitic disease.

PMID- 27876937
TI  - Clinical management of demodicosis in Ongole cattle.
AB  - Demodicosis was diagnosed in a cattle based on dermatological lesions and
      examination of skin scrapings. The cattle had anaemia, leucocytosis, eosinophilia
      and neutrophilia. Cattle was treated with strepto penicillin, ivermectin, amitraz
      along with supportive therapy. After 2 months of therapy clinical cure and
      regrowth of hair was noticed.

PMID- 27876938
TI  - Polymerase chain reaction (PCR) based amplification of hmcp3 and hmcp6 cysteine
      protease genes of Haemonchus contortus from small ruminants.
AB  - Haemonchus contortus is a haematophagous nematode in small ruminants population
      and causes anaemia, weakness and mortality especially in young animals. In the
      present study, hmcp3 partial gene of 836 bp and hmcp6 full length gene of 1041 bp
      were amplified from the cDNA of Bareilly isolate of adult male H. contortus by
      polymerase chain reaction. Further gene characterization and expression studies
      are warranted to know the immunoprophylactic potential of hmcp3 and hmcp6
      proteins of H. contortus.

PMID- 27876939
TI  - Molecular detection of Toxoplasma gondii in house sparrow (Passer domesticus) by
      LAMP and PCR methods in Tehran, Iran.
AB  - Toxoplasma gondii is one of the most common zoonotic parasitic diseases in human
      and warm-blooded animals worldwide. Birds are one of important intermediate hosts
      of T. gondii. The aim of this study is molecular detection of T. gondii in the
      house sparrow by LAMP and PCR methods in Tehran, Iran. A total 200 sparrows were
      captured in different regions of Tehran. DNA was extracted from tissue samples of
      each sparrow. LAMP and conventional PCR assays were carried out with a set of
      primers to detect the 529 bp fragment of T. gondii. LAMP and PCR were detected T.
      gondii from 17 (8.5 %) and 15 (7.5 %) of 200 sparrows respectively. These results
      indicated that sensitivity of LAMP was higher than conventional PCR. In our
      knowledge, this study is the first report of detection of T. gondii by LAMP
      method in bird hosts. Also, these findings provided an insight into
      epidemiological pattern of T. gondii infection in sparrow in Iran.

PMID- 27876940
TI  - Echinococcus granulosus in humans associated with disease incidence in domestic
      animals in Kermanshah, west of Iran.
AB  - Hydatidosis is one of the important zoonotic diseases that cause considerable
      economic losses and public health problems worldwide. This study was conducted to
      determine the prevalence Echinococcus granulosus in people and slaughtered
      animals in Kermanshah province, west of Iran. Hospitals data and meat-inspection
      records in Kermanshah abattoir were used in this study. A total number of 32,130
      slaughtered livestock (7000 cattle, 19,950 sheep and 5180 goats) was inspected in
      the 3-year period and overall 2043 (6.35 %) were infected. The highest and lowest
      prevalence was recorded in cattle and goats, respectively. In human, Cystic
      echinococcosis affected more females (54 %) than males (46 %) with a 1.17 male to
      female ratio. Rate of disease in urban and rural regions were 46 and 54 %,
      respectively. The youngest and the oldest patient operated were 7 and 87 years
      old, respectively, and the age group 21-40 years (41.2 %) were the most affected.
      A significantly higher number of hydatid cysts were recorded in the liver than in
      other sites. The ratio of hepatic hydatidosis to pulmonary hydatidosis was 2.46.
      The results showed that hydatidosis is of great importance in this area and
      serious attention is needed to prevent and control the disease.

PMID- 27876941
TI  - Toxocara vitulorum in a suckling calf: a case study.
AB  - The present clinical case reports toxocariosis in a suckling calf and its
      management. One and a half month old crossbred Jersey calf was presented at a
      Veterinary Clinics, District Pulwama, Kashmir with a history of intermittent
      diarrhea, poor growth, weakness, moderate dehydration and anorexia. On
      inspection, the calf showed normal physiological parameters viz; body
      temperature, pulse rate and respiration rate. On faecal examination, eggs of
      Toxocara vitulorum were found. The animal was treated with 30 ml suspension of
      1.5 % fenbendazole + 0.5 % praziquantel orally. After examination of faecal
      samples on 7th and 14th day post treatment no T. vitulorum eggs were observed.

PMID- 27876942
TI  - Prevalence of Enterobius vermicularis amongst kindergartens and preschool
      children in Mazandaran Province, North of Iran.
AB  - Enterobiasis (oxyuriasis) is probably the most common helminth, which infects
      humans. Amongst different age groups, prevalence of Enterobius vermicularis in
      children is high compared to adults. Oxyuriasis is one of the most significant
      parasitic diseases of children. This nematode in children can result in loss of
      appetite, insomnia, grinding of the teeth, restlessness, endometritis, abdominal
      cramps, diarrhea and etc. Due to important complications of this parasite, the
      objective of the current study was to determine the prevalence of enterobiasis in
      kindergarten and preschool children of Amol, Mazandaran Province, North of Iran.
      A total number of 462 children from 32 kindergartens of Amol were examined for
      the prevalence of E. vermicularis infection, 2013. Adhesive cello-tape anal swab
      method was trained to parents for sampling. In addition, a questionnaire was
      designed and filled out to collect demographic information for each individual.
      Data were analyzed using Chi square test and multivariate logistic regression for
      each risk factor. The overall prevalence of E. vermicularis infection was 7.1 %
      (33). Although infection with E. vermicularis in girls 7.9 % was higher compared
      to boys 6.3 %, there was no significant difference between gender and age (p >
      0.05) whereas binary logistic regression showed significant difference between
      enterobiasis and age (p < 0.05). The findings indicated that the prevalence of E.
      vermicularis in kindergarten and preschool children is relatively high and still
      is an important health problem and should not be underestimated due to being
      highly contagious infection. Therefore, educational programs and mass treatment
      should be carried out in order to reduce infection incidence in this area and
      regular parasitological test and attention to personal hygiene in kindergarten
      and preschool is of great importance.

PMID- 27876943
TI  - Hematological characteristics associated with parasitism in Pikeperch Sander
      lucioperca (Percidae) from Anzali Wetland.
AB  - A total of 120 Sander lucioperca (Percidae) were captured and investigated for
      parasites and also haematological parameters were analysed and compared between
      infected and uninfected fish. The haematological analysis showed reductions in
      haematocrit, haemoglobin, red blood cell, whereas with blood cell (WBC) and
      lymphocyte significantly increased (P < 0.05) in infected fish, whereas with
      blood cell (WBC) and lymphocyte significantly increased (P < 0.05) in infected
      fish. Parasitological inspections revealed the following infestations:
      Eustrongylides excisus (Nematoda), Dactylogyrus sp. (Platyhelminthes) and
      Achtheres percarum, Diplostomum spathaceum (Platyhelminthes) and Trichodina sp.
      (Ciliophora). The prevalence and intensity of the infection with parasites were
      varied at age groups of host. Significant differences were found for the white
      blood cell and lymphocyte in relation to parasitism. Parasitism had no influence
      on studied blood parameters of S. lucioperca in natural conditions.

PMID- 27876944
TI  - Seasonal incidence of parasitic diseases in bovines of south western Gujarat
      (Junagadh), India.
AB  - The current study was conducted to investigate the incidence of parasitic
      diseases in bovines which were sick and brought at veterinary hospital for
      treatment. A total of 366 samples were investigated from cattle (n = 175) and
      buffaloes (n = 191) presented at Teaching Veterinary Clinical Complex (TVCC),
      Veterinary College, Junagadh, Gujarat during January to December 2014.
      Examination of Giemsa-stained peripheral blood smears exhibited that 58.6 % of
      cattle and 41.2 % of buffaloes were infected with haemoparasites comprising
      Babesia bigemina, Theileria annulata, and Anaplasma marginale @ of 54.0, 3.4 and
      1.1 in cattle and 38.8, 1.2 and 1.2 percent in buffaloes, respectively. The
      incidence of total haemoparasites and B. bigemina infections was significantly
      higher (p < 0.05) in cattle whereas, incidence of haemoparasites were recorded
      significantly higher in the month of July to November (i.e., rainy and autumn) in
      both cattle and buffaloes, respectively (p < 0.01 and p < 0.001). Coprological
      examination revealed that the overall incidence of gastrointestinal (GI)
      parasitic infection was 45.5 % in cattle and 43.4 % in buffaloes. The incidence
      of individual parasite was 11.4, 1.1, 2.3, 4.5, 1.1, 3.4, 2.3 and 19.3 in cattle
      and 4.7, 0.9, 0.0, 2.8, 0.9, 5.7, 0.0 and 28.3 % in buffaloes for Eimeria spp.,
      Trichuris spp., Toxocara vitulorum, Strongyle, Fasciola spp., amphistomes,
      Schistosoma indicum and Buxtonella sulcata, respectively which differ
      insignificantly (p > 0.05). Seasonal prevalence of GI parasites was highest in
      summer in both cattle and buffaloes, the data being statistically non-significant
      (p > 0.05). However, the incidence of B. sulcata in both cattle (19.3 %) and
      buffaloes (28.3 %) was higher in comparisons to other GI parasites. The present
      investigation emphasized that B. bigemina and B. sulcata are the most important
      parasites of bovines of this region.

PMID- 27876945
TI  - A case of fatal gastrointestinal haemorrhage due to hyperinfection with
      Strongyloides stercoralis.
AB  - Strongyloides stercoralis is an intestinal nematode with a complex life cycle. It
      is usually asymptomatic in healthy host however it may be a life threatening
      condition in immunocompromised patients when hyperinfection is associated with
      disseminated disease. However, reports of gastric involvement are rare. This is a
      case report of fatal gastrointestinal hemorrhage due to hyperinfection with S.
      stercoralis in a Burmawi male patient after brief corticosteroid therapy.

PMID- 27876946
TI  - Evaluation of clinical, biochemical and haematological markers in natural
      infection of canine monocytic ehrlichiosis.
AB  - Caanine monocytic ehrlichiosis caused by Ehrlichia canis has gained wider
      significance owing to its potential to inflict significant deleterious effect on
      the health of companion animals. In the present study, 46 confirmed ehrlichiosis
      positive dogs were evaluated for the alterations in clinical, haematological and
      biochemical attributes. Depression, anorexia, pyrexia, anaemia, weakness,
      jaundice, melana, vomition and diarrhoea were the main clinical symptoms
      onserved. Haematological alterations included pancytopenia especially
      thrombocytopenia. Significant changes were noticed in WBC, RBC, Hgb, McHc,
      Platelets, ALT values while rest all the studied haematological and biochemical
      parameters showed non-significant alterations within normal range in comparison
      to normal healthy controls. The findings substantiate that ehrlichiosis cause
      significant clinical, haematological and biochemical alterations of the varied
      intensity in dogs, even with lower grades of parasitaemia.

PMID- 27876947
TI  - A survey on parasites of long-eared hedgehog (Hemiechinus auritus) in northeast
      of Iran.
AB  - As there appeared to be no data available on parasite infection of Hedgehogs in
      the region and considering the potential threat of Hedgehogs for animal and
      public health, the present study was carried out using biological samples and
      necropsy findings collected from long-eared hedgehog captured in Mashhad city in
      the northeast of Iran. During the study 23 dead hedgehogs were collected randomly
      from different regions of Mashhad County. Following autopsy of these animals,
      observation for enteric parasites was carefully done. At the same time, 38 live
      hedgehogs were captured at this region and after anesthetizing of them, their
      ectoparasites were removed. The captured animals were released after recovery.
      All of studied animals were found to be infected with at least one of the
      parasites. The endoparasites removed from dead hedgehogs were: Oliganthorhynchus
      erinacei, Nephridiorhynchus major, Hymenolepis erinacei and Crenosoma striatum.
      The ectoparasites found on live studied animals according to their abundance were
      Rhipicephalus turanicus,Haemaphysalis erinacei and Echidnophaga gallinacea. The
      results of this study will contribute to our understanding of the parasites
      infecting Hemiechinus auritus in Iran. These results also suggest that pet owners
      especially those keep hedgehog should be aware about hazards that may pose by
      these animals.

PMID- 27876948
TI  - Assessment of risk factors associated with prevalence of coccidiosis in dairy
      animals of Punjab.
AB  - A total of 2089 faecal samples (956 buffaloes and 1133 cattle) were collected
      from 21 districts of five major agro-climatic zones of Punjab during April, 2013
      May, 2014. An overall prevalence rate of 32.17 % (672/2089) was recorded for
      coccidiosis in dairy animals with a significantly higher (P < 0.01) infection
      rate in buffaloes (35.46 %) in comparison to cattle (29.39 %). Quantitative
      analysis revealed oocyst per gram of faeces ranging from 200 to 10,000 (1083.72
      +/- 227.20) and 100 to 2400 (748.72 +/- 81.38), in cattle and buffalo
      populations, respectively. The results of multivariate analysis showed that
      prevalence of coccidiosis in cattle population was associated with various risk
      factors viz. districts (P = 0.000; OR 2.749; 95 % CI 1.238-6.107), agro-climatic
      zones (P = 0.004; OR 2.707; 95 % CI 1.707-4.293) and seasons (P = 0.000; OR
      1.106; 95 % CI 0.811-1.509). Similarly, in buffalo population an association with
      districts (P = 0.000; OR 2.163; 95 % CI 0.702-6.668), agro-climatic zones (P =
      0.000; OR 1.237; 95 % CI 0.673-2.277) and seasons (P = 0.100; OR 1.382; 95 % CI
      1.003-1.903) was recorded. The findings of the current study would provide a
      basis for evolving effective control strategy for the management of coccidiosis
      in dairy animals of the region.

PMID- 27876949
TI  - New occurrence of parasitic isopod Argathona sp. (Stebbing, 1905) from
      Epinephelus undulosus in the Tuticorin coast, Gulf of Mannar region.
AB  - In the present study of Epinephelus undulosus captured in gillnets from the
      inshore waters of Tuticorin, Gulf of Mannar region during December 2014. The
      present findings represent the first occurrence of Argathona sp. and here in
      reported. The materials examined were deposited at the Kamaraj College, Marine
      Biological Research Laboratory, Tuticorin, India. The parasitological indexes
      were calculated. The site of attachment of the parasites on their hosts was also
      observed. Host-parasite relationships are considered and these parasites can
      cause the damage in gill, eye and internal organ including swim bladder. Marine
      fish parasitology is a rapidly developing field of aquatic science.

PMID- 27876950
TI  - A note on concurrent natural parasitism by Dispharynx spiralis and Heterakis
      gallinarum in backyard poultry (Gallus domesticus).
AB  - The nematodes Dispharynx spiralis (Superfamily-Spiruroidea, Family-Acuariidae)
      parasitising the proventriculus and Heterakis gallinarum (Superfamily
      Subuluroidea, Family-Heterakidae) found in the caecum of two backyard poultry
      birds are described. The usual location of D. spiralis is glandular stomach or
      proventriculus, where their heads may be deeply buried in the proventricular
      wall. H. gallinarum occurs in the caecum and commonly called as caecal worm of
      poultry.

PMID- 27876951
TI  - Prevalence of Dermanyssus and Ornithonyssus species of mites in poultry farms of
      Vikarabad area of Hyderabad.
AB  - The common blood feeder mites of poultry are from the genera Dermanyssus and
      Ornithonyssus. Their presence are problematic for the producers either through
      potential direct effects on weight gain, egg production or sperm production in
      roosters or as nuisance pests on workers. They also cause anaemia in birds and
      play a vector role for several human and animal diseases. Five poultry farm
      buildings of Vikarabad area of Rangareddy district were visited. Samples were
      collected from a variety of sites, including beneath feed troughs, inside cage
      fittings and fastening clips, under egg conveyer belts and under manure belts.
      Heavily mite infested feathers were plucked from three to five individual birds
      and kept in closed plastic covers. Samples were processed and mounted permanently
      by using DPX and species differentiation was done. Besides this litter materials
      and soil samples from the farm were also collected. Massive mixed infestations of
      Dermanyssus and Ornithonyssus mites were found. The morphological characters
      provided here can be considered as a practical tool for species differentiation
      and as these blood feeder mites were most prevalent and important pests of
      poultry, public health aspects of these parasites should be considered.

PMID- 27876952
TI  - Gastrointestinal helminth parasites of local chickens from selected communities
      in Nsukka region of south eastern Nigeria.
AB  - The prevalence of gastrointestinal helminths of local chickens in Nsukka region
      of Southeastern Nigeria was studied using 125 free range local birds purchased
      from four communities in Nsukka zone namely, Obollo-afor, Orba, Nsukka urban and
      Owerre Eze-orba. The birds were sacrificed humanely and their oesophagus, crop,
      proventriculus, gizzard, small intestine and caecum examined for the presence of
      gastrointestinal helminths. Worms when present were isolated and identified using
      standard parasitological procedures. The study identified four species of
      cestodes namely Raillietina echinobothridia, R. tetragona, R. cesticillus and
      Choanotaenia infundibulum and two species of nematodes namely, Ascaridia galli
      and Heterakis gallinarum. Results obtained showed 96.8 % prevalence of
      gastrointestinal helminth parasites in the birds with cestodes being the more
      prevalent class (70.4 %). Raillietina spp was the most prevalent cestode
      encountered and A. galli the most prevalent nematode. Prevalence rates of
      infections recorded 14.4 % for nematode species, 26.4 % for cestodes and 56 % for
      mixed infections of nematodes and cestodes. It was concluded that local chickens
      are common in the area and could serve as a potential source of helminth
      infections to intensively managed birds in the study area.

PMID- 27876953
TI  - Assessment of risk factors associated with prevalence of strongyle infection in
      equines from Central Plain Zone, Punjab.
AB  - A total of 311 equine faecal samples (190 horses and 121 mules) collected from
      six districts of Central Plain Zone, Punjab were examined using standard
      coprological methods. The results showed an overall prevalence of 27.33 % for
      strongyles with rare to mild type of infection as evident from egg per gram of
      faeces. In particular, amongst the examined samples, 17.90 % of horses and 42.14
      % of mules were infected and the difference was statistically significant (P <
      0.01). Identification of the faecal culture harvested larval stages, showed 56 %
      and 46 % of horses and mules, respectively, positive for small strongyles
      (Cyathostomes). Amongst the large strongyles, highest proportion was recorded for
      Strongylus vulgaris whereas, S. equinus was found in least proportion. Results
      indicated that the various risk factors viz. area, season, age and sex of the
      host had no significant effect on prevalence of strongyle infection in equines.

PMID- 27876954
TI  - High prevalence and infestation of Mothocya renardi (Isopoda, Cymothoidae) in
      marine fish Strongylura leiura (Bleeker 1850).
AB  - Cymothoid isopods are parasites that cause severe damage to the fish species. The
      present study was focused to carry out the parasitic infestation on the one of
      the important marine fish Strongylura leiura during the 2 years period between
      June 2009 and May 2011. 272 fish specimens collected and about 157 (57.72 %)
      fishes were infested by the cymothoid which were concealed under the gill arches
      of the host. Infested parasite was identified as Mothocya renardi. The prevalence
      rate of parasites during different seasons of the range of host specificity of
      isopods was studied. Variation of infestation rate also depends on the size,
      length and weight of the host. The sites of infestation by the parasitic
      crustaceans are highly specific. The infestation had affected the normal growth
      of the host fish and also probably leads the high levels of secondary infections.

PMID- 27876955
TI  - Response of unfed stages of Rhipicephalussanguineus to subtle variations in the
      composition of assembly pheromone.
AB  - Two combinations of assembly pheromone (AP), with and without hematin were
      utilized as a lure for the unfed larvae, nymph and adults of
      Rhipicephalussanguineus ticks. In-vitro trials were carried out with the AP
      encapsulated in calcium alginate beads and the response of different stages of
      ticks were recorded. Analysis of results revealed that rapid attraction was
      evident in unfed larvae exposed to beads containing AP without hematin. In case
      of unfed nymphal and adult stages, the presence or absence of hematin did not
      have any impact on arrestment.

PMID- 27876956
TI  - Comparison between in-house indirect ELISA and Dot-ELISA for the diagnosis of
      Fasciola gigantica in cattle.
AB  - This survey was done to investigate the efficacy of the in-house indirect ELISA
      (iELISA) and Dot-ELISA methods Prepared from excretion-secretory (ES Ag) and
      Crude (Cr Ag) antigens of Fasciola for sero-diagnosis of Fasciola gigantica in
      cattle. The liver specimens of slaughtered cattle were collected and their liver
      examined macroscopically and microscopically for infestation to fasciolosis. Sera
      from two groups of cattle, one infected with fasciolosis (n = 60) and the other
      non-infected with fasciolosis (n = 60), were used in the iELISA and Dot-ELISA
      test; grouping based on histopathology results. Except specificity, other
      parameters such as, sensitivity, accuracy, positive and negative predictive
      values of both Dot-ELISA and iELISA done with ES Ag were better than those of
      tests performed with Cr Ag. Interestingly, the reliability of two methods was
      very good similar to one another.

PMID- 27876957
TI  - Diagnosis of cystic echinococcosis in buffaloes by native 8 kDa antigen using
      latex agglutination test (LAT).
AB  - The dog tapeworm Echinococcusgranulosus is the causative agent of cystic hydatid
      disease in domestic/wild herbivores animals and man. Accurate immunodiagnosis of
      the infection requires highly specific and sensitive antigens. The aim of this
      study was to develop and evaluate immunoassays with principles of precipitation,
      agglutination for the identification of buffaloes infected with hydatid cyst
      which would allow the monitoring of animals from endemic areas and identifying
      infected animals prior to slaughter. The immunoassays were developed and
      validated using hydatid specific, non-cross reactive low molecular weight 8 kDa
      hydatid cyst fluid protein. Sera used for the assay validations were obtained
      from 200 buffaloes infected naturally with hydatid cyst and 200 non-infected
      buffaloes. The diagnostic sensitivity with latex agglutination test was 98.67 %.
      It should be useful for the conformation of hydatid cyst infected individual
      sheep.

PMID- 27876958
TI  - Effect of Haemoproteus columbae infection on the hemogram of the Pigeons (Columba
      livia domestica).
AB  - It has been reported that parasites affect the health and productivity of birds,
      initiate excessive preening which interrupts feeding, as the birds spend much
      time preening rather than being involved in other essential life activities.
      Haemoproteuscolumbae occurs in pigeons widely in tropical and subtropical
      regions. The present investigation was concentrated on the effect of H. columbae
      infection on the hemogram and changes in the number of white blood cells in
      infected pigeons. Blood samples taked from 100 pigeons in Shahrekord. Blood
      smears stained and observed for H.columbae infection. Packed cell volume (PCV)
      and total white blood cells (WBC) count and differential WBC count determinate
      for every smears. This study show that PCV increased in infected pigeons by H.
      columbae than non infected pigeons. There were increasing in the number of total
      WBC in the infected pigeons by H. columbae than non infected pigeons. Also there
      were significant differences between the number of lymphocytes and eosinophils in
      the infected pigeons by H. columbae than non infected pigeons. This study and
      same studies show the part of the effects of blood parasites on the hemogram, but
      there were many questions about the effects of blood parasites such as H.
      columbae on the other parameters of host's blood, so we advise to focus on the
      other hematological parameters in the future studies.

PMID- 27876959
TI  - A rare cause of dysphagia: pharyngeal ascariasis.
AB  - Ascaris lumbricoides infection distributed widely in tropical and subtropical
      areas, especially in the developing countries and affects more than one billion
      of people. Ascariasis commonly has higher infection rates compared to other
      parasite species and because of poor sanitation the parasite can be seen in 100 %
      of the population. A. lumbricoides depending on the provocation by anesthetic
      agents or intestines becomes hostile, such as with inflammation and obstruction,
      may cause migration and varies complications such as coming up to the mouth or
      blocking some ducts. We report a case of pharyngeal ascariasis with worm
      migration, in a 67-year-old woman was referred with complaints of nausea and
      dysphagia.

PMID- 27876960
TI  - Characterization and control of symbiotic Bacillus cereus isolated from the mid
      gut of Anopheles subpictus Grassi.
AB  - An investigation was done to find out the role of gut bacterium on the larval
      development and survival of Anopheles subpictus, the vector responsible for the
      transmission of malaria. An. subpictus mosquitoes breed exclusively in stagnant
      water, including shrimp/fish ponds with high nutrient level. One bacterial strain
      (CX2) was isolated from the midgut of late third instar of mosquito larvae. The
      bacterial isolate was sensitive to recommended doses of tetracyclin (30 ug/disc),
      doxycycline (30 ug/disc), kanamycin (30 ug/disc), gentamycin (10 ug/disc),
      streptomycin (10 ug/disc), vancomycin (30 ug/disc), ofloxacin (5 ug/disc),
      levofloxacin (5 ug/disc), gatifloxacin (10 ug/disc), but resistant to ampicillin
      (10 ug/disc).The larvae which were fed with the mixture of two antibiotics
      tetracylin (30 ug/disc) and doxycyclin (30 ug/disc) (1:1) could not survive in
      rice-field water. In the control experiments without any antibiotic treatment, 95
      100 % survival and 95 % adult emergence were observed. The study indicates that
      the elimination of gut bacteria suppressed larval growth. Phylogenetic analysis
      of the 16S rRNA gene sequence was also done. Based on the morphological,
      biochemical, FAME analysis and phylogenetic analysis, the bacterial isolate CX2
      was identified as Bacillus cereus. Poly acrylamide gel electrophoresis analysis
      revealed that the isolate showed discrete bands ranging from 24.272 to 60.049 kDa
      proteins. Water extract and methanol extract of Tamarindus indica showed
      inhibitory effect against B. cereus.

PMID- 27876961
TI  - Intestinal helminth infections among children of district Shopian of Kashmir
      Valley, India.
AB  - Intestinal helminth infections are amongst the most common infections worldwide.
      Studies in other districts of Kashmir Valley revealed a high prevalence of
      intestinal helminth infections among the children. The objectives of the current
      study were to determine the prevalence of intestinal helminth infections among
      children of Shopian district and to identify associated socio-demographic and
      environmental actors, behavioral habits and also related complaints. Stool
      samples were collected from 352 children and a questionnaire was filled for each
      case. The samples were processed using both simple smear and zinc sulphate
      concentration methods, and then microscopically examined for intestinal
      helminths. Of the 352 children surveyed, 75.28 % had 1, or more, helminth
      parasites. Prevalence of Ascaris lumbricoides was highest (71.8 %), followed by
      Trichuris trichiura (26.4 %), Enterobius vermicularis (13.9 %) and Taenia
      saginata (5.3 %). Conditions most frequently associated with infection included
      the age group, water source, boiled or unboiled water, defecation site, personal
      hygiene, and the extent of maternal education. The study shows a relatively high
      prevalence of intestinal helminths and suggests an imperative for the
      implementation of control measures.

PMID- 27876962
TI  - Diagnosis and therapeutic management of Dipylidium caninum in dogs: a case
      report.
AB  - The present study is related to Dipylidium caninum infection in dogs. Three dogs
      about 1 year of age with the history of scooting behaviour and passing diarrhoeic
      stool containing white specks were presented before the clinicians. Physical
      examination of dogs revealed flea infestation and faecal examination revealed the
      presence of gravid segments, which were confirmed microscopically to be of
      cestode, D. caninum. Dogs were treated with Praziquantel@5 mg/kg body wt. orally.
      Dogs showed marked recovery post treatment. On re-examination after a week,
      faeces were found negative for any parasitic eggs/gravid segments.

PMID- 27876963
TI  - Ultrastructural study of Apiosoma piscicola Blanchard, 1885 (Subclass:
      Peritrichia) on Tachysurus fulvidraco from China.
AB  - This paper gave detailed description of the fine structure of Apiosoma piscicola
      Blanchard 1885. These parasites were collected from the fry of Tachysurus
      fulvidraco during parasite surveys of fish at Jiangxia Fish Hatchery in Wuhan,
      Hubei province in May 2011. Its pellicle, peristomial apparatus, nuclei, trochal
      band and scopula were described, respectively. The relationship between these
      peritrich ciliates and their hosts was well discussed herein. The scopula of A.
      piscicola did not adhere directly to the surface of the host epithelial cells,
      but by means of a secreted adhesive pad of material according to the present
      study. Besides, no ultrastructural damage to host epithelial cells could be
      detected in our work. We concluded that these sessilids should be ectocommensals
      rather than ectoparasites, but not always harmless. In addition, their great
      variability of body shape and non-strict host specificity were also discussed.

PMID- 27876964
TI  - Patho-physiological observations in natural concurrent infections of helminth
      parasites of zoonotic importance in the wild rodents, Bandicota bengalensis.
AB  - Screening of 83 mature wild rodents of Bandicota bengalensis (52 male and 31
      females), live trapped from premises near railway station, fish market and
      agricultural fields in Ludhiana district of Punjab province, India was carried
      out to assess the natural occurrence of helminth parasites and their potential as
      reservoirs of zoonoses. On necropsy, intestine of rats was found infected with
      adult cestode parasites of Hymenolepis diminuta and H. nana. Liver was found
      infected with Capillaria hepatica and Cysticercus fasciolaris. These parasites
      were present either alone or as concurrent infection. In overall, 68.67 % rats
      were found infected of which 59.65 % were infected with nematode parasite, C.
      hepatica and 75.44 % with cestode parasites. Grossly, pathognomonic lesions of C.
      hepatica and C. fasciolaris were seen clearly and microscopic changes were
      observed only in severely infected cases. Overall investigation on the effect of
      these parasitic infections on pathophysiology of the host revealed that rodents
      serve as reservoirs of these parasitic infections without having much pathogenic
      effect on their vital organs, fecundity and enzyme activities. Because of its
      close association with human habitations, B. bengalensis may act as an important
      source of zoonotic infections and thus direct or indirect contact with excrements
      and carcasses of this rodent species, should be avoided.

PMID- 27876965
TI  - Histopathological study of gill, kidney and liver of Persian Sturgeon (Acipenser
      persicus Borodin, 1897) and Stellate (Acipenser stellatus Pallas, 1811) exposed
      to sublethal concentration of un-ionised ammonia UAN.
AB  - This study was carried out to investigate the histopathological changes of gill,
      kidney and liver of Persian Sturgeon and Stellate in response to various
      sublethal concentration of ammonia. The sublethal doses were determined after a
      lethal pre-test and then the experiment was done in six treatments with three
      replicates for both species. In Persian sturgeon, the treatments were including
      5, 7, 9.7, 13.2, 18 and 25 mg/l ammonia. In stellate, the concentrations of 5,
      6.23, 7.76, 9.66, 12.04 and 15 mg/l ammonia were considered as treatments. Also,
      one group without ammonia was considered as control for each experiment. The
      histopathological investigations were done after 96 h exposure. According to our
      observations, a range of histopathological alternations were found in gill, liver
      and kidney of both examined fish. The alternations of gill tissue were lamellar
      necrosis, hyperplasia, lamellar adhesion, haemorrhage, swelling of gill lamellae.
      Severity of these alternations was dose-dependent and was significantly higher in
      Persian sturgeon than in stellate. The degree of histopathological alternations
      of liver did not show a regular pattern between treatments in both species. These
      alternations were hyperemia, bile record, cell necrosis, cell atrophy, fatty
      degeneration and cloudy swelling. The signs of kidney alternations intensified
      with increasing of ammonia concentration in both species. The signs such as
      hyperemia, vision tissue degeneration, cell necrosis, dilatation of Bowman's
      space. In conclusion, our results showed that ammonia in concentration of more
      than 5 mg/l have more adverse impacts on gill, liver and kidney tissues.

PMID- 27876966
TI  - Evaluation of sodium fluoride toxicity in Schistosoma infected snails: assessment
      of antioxidants, antiapoptotic, hypoprotein and hypocholesterol activities.
AB  - The snails' tissues represents an intermediate or secondary host for Schistosoma
      sporocysts where, germ cells within the secondary sporocyst begin to divide to
      produce thousands of cercariae capable of infecting humans. The aim of the study
      was to evaluate the toxicity of sodium fluoride in Schistosoma snails' tissue
      homogenates. A total number of 264 different Schistosoma snails were collected
      from eight drainage water resources and divided into control uninfected and
      infected snails; where infected snails divided into four group; the first group
      without any treatment while second, third and fourth groups immersed in 25, 50
      and 100 mg sodium fluoride/L during the period of 4 weeks then the snails'
      hemolymph and tissue homogenates were prepared to evaluate the snail' tissue
      antioxidants, protein content, lipid profile and apoptosis. The results obtained
      revealed that superoxide dismutase, glutathione-S-transferase, glutathione
      peroxidase, catalase, reduced glutathione, glutathione reductase levels were
      decreased while malondialdehyde, protein carbonyl, total protein, albumin,
      globulin, cholesterol, low density lipoprotein and triglycerides levels were
      increased in Schistosoma infected snails' tissues. Schistosoma also induced
      apoptosis in snails' tissues homogenates. Sodium fluoride restores all the above
      parameters to approach the control uninfected snails levels. In conclusion,
      sodium fluoride inhibits oxidative stress and apoptosis produced in Schistosoma
      infected snails and consequently it is be useful to be used in Schistosoma
      infection inhibition where sodium fluoride at higher dose was more effective than
      the lower two doses.

PMID- 27876967
TI  - In vivo effect of anti-TNF agent (etanercept) in reactivation of latent
      toxoplasmosis.
AB  - Toxoplasma gondii (T. gondii), an intracellular parasite, establishes a chronic
      infection by forming cysts preferentially in the brain. TNF-alpha plays an
      important role in controlling the infection caused by this protozoan. Thus, the
      blockade of TNF-alpha could cause reactivation of latent toxoplasmosis infection
      as well as increase the risk of acute toxoplasmosis. This study evaluated the
      effect of etanercept, a TNF-alpha antagonist in reactivation of latent
      toxoplasmosis compared to the therapeutic effect of sulfadiazine and
      pyrimethamine in combination on the progress of the disease. A total of 40
      laboratory-bred Swiss albino mice were infected with Me49 strain of T. gondii and
      divided into four groups: infected control group; treated group with sulfadiazine
      and pyrimethamine; treated group with etanercept and treated group with both
      etanercept and sulfadiazine and pyrimethamine. The mean number and size of tissue
      cysts in brain smears of mice of each group were determined and also, serum
      levels of TNF-alpha were assessed in different study groups by an enzyme linked
      immunosorbent assay. The results showed that the mean TNF-alpha level was
      significantly different in the treated groups compared to that in infected
      control group. The highest level of TNF-alpha was found in the infected controls.
      After treatment with etanercept alone or combined with sulfadiazine and
      pyrimethamine, it was significantly decreased. In this study, reactivation of
      latent toxoplasmosis was observed by a significant increase in the mean number
      and sizes of Toxoplasma tissue cysts in brains of mice with established chronic
      toxoplasmosis after treatment with etanercept alone or combined with conventional
      treatment compared to both untreated chronically infected controls and infected
      mice treated with sulfadiazine and pyrimethamine. It was concluded that
      etanercept, a TNF-alpha antagonist may play a role in reactivation of latent
      toxoplasmosis. So, serological screening for toxoplasmosis might offer a valuable
      aid for patients treated with this drug.

PMID- 27876968
TI  - Detection of Toxoplasma gondii in small ruminants in Chennai using PCR and
      modified direct agglutination test.
AB  - A total of 193 sera samples, along with tissues (lung, heart, and brain)
      collected from 136 sheep and 57 goats from the Corporation slaughter house,
      Madras Veterinary College teaching hospital, and private mutton shops from
      Chennai were tested for Toxoplasma gondii. All the sera samples were tested using
      modified direct agglutination test. Of the 193 sera samples, 57 (29.5 %) had a
      minimum titre of 1:20, with 30.14 % (41/136) of sheep and 28.07 % (16/57) of
      goats being seropositive. Tissue samples from all 193 animals, when subjected to
      B1 based PCR to detect T. gondii DNA, showed 3.67 and 3.50 % to be positive in
      sheep and goats, respectively. In the present investigation B1 based PCR detected
      T. gondii in low numbers, possibly due to limitation of the sample size. The
      presence of T. gondii in tissues of sheep and goats slaughtered for human
      consumption in Chennai indicates the role of these food animals as potential
      sources of infection to human.

PMID- 27876969
TI  - Molecular detection of giardiasis among children at Cairo University Pediatrics
      Hospitals.
AB  - Giardiasis is a prevailing intestinal disease in children. This study aimed to
      determine molecular prevalence of Giardia intestinalis in children attending
      Cairo University Pediatrics Hospitals, using copro-PCR assays, conventional
      methods and to evaluate diagnostic effectiveness of used tests. 229 fecal samples
      were collected from children suffering from gastrointestinal symptoms and
      examined for Giardia by microscopy, Immuno-chromatographic test (ICT), copro-DNA
      using two PCR assays targeting tpi [nested-PCR (nPCR)] and 18S [conventional-PCR
      (cPCR)] genes. Out of 229 samples assessed, Giardia was diagnosed in 13.9, 17,
      17.9, 4.8 % of cases using microscopy, ICT, nPCR (tpi) and cPCR (18S),
      respectively. Nominating both PCR assays as composite reference standard,
      microscopy and ICT were of reliable specificity (100 and 96.9 %) and accuracy
      (95.6 and 93.6 %) but of limited sensitivity (78.6 and 76.2 %). Kappa agreement
      showed, there was substantial agreement of ICT (0.776) and almost perfect
      agreement of microscopy (0.839) with PCR assays. Giardia showed a molecular
      prevalence of 18.3 % (42/229). ICT assay for Giardia surpassed microscopy but
      both couldn't be used as a consistent single detection method due to their
      lowered sensitivities. nPCR targeting tpi is a reliable diagnostic test aiding to
      determine true prevalence of Giardia.

PMID- 27876970
TI  - Larvicidal activity of camphor and lavender oils against sheep blowfly,
      Luciliasericata (Diptera: Calliphoridae).
AB  - In this study, the essential oils of camphor and lavender were tested in vitro
      against the third instar larvae of Lucilia sericata for the first time, following
      dipping toxicity technique. The toxicity results revealed that L. sericata larvae
      were susceptible to the applied essential oils. Lavender oil was more effective
      than camphor in killing of L. sericata larvae. With 32 % concentration, the
      mortality percentages of larvae were 100 and 93.3 %, respectively. Light and
      scanning electron microscopic examinations were done to determine the cuticular
      changes of L. sericata larvae following exposure to the applied essential oils.
      Larvae showed cuticular swelling and distortion after oil treatment, but its
      level was greater with lavender oil. The current study suggested that an
      alternative, effective and natural product can be developed as larvicides against
      L. sericata using camphor and lavender oils.

PMID- 27876971
TI  - Isolation of Acanthamoeba spp. from different water sources in Isfahan, central
      Iran, 2014.
AB  - Acanthamoeba spp. are free-living amoeba found in a wide variety of natural
      habitats. The high percentage of the presence of Acanthamoeba in different
      environmental sources represents a sanitary risk for public health, especially
      immunocompromised patients and contact lens wearers. Acanthamoeba can cause
      granulomatous amoebic encephalitis, otitis, lung lesions, and skin infections in
      individuals with immune deficiencies. In the present study, the status of
      contamination of water sources in Isfahan, central Iran is analyzed through
      parasitological method. Totally 93 samples were utilized consisting of 59 samples
      of tap water and 34 samples of environmental water collected from Isfahan in May
      and June 2014. After filtering, cultivation was done in non-nutrient agar medium,
      and then the cultured media were kept at 25-30  degrees C. The samples were
      analyzed based on the morphological criteria. Acanthamoeba spp. were found in 25
      (73.53 %) out of 34 environmental water samples and 17 (28.8 %) out of 59 tap
      water. Generally, Acanthamoeba spp. were found in 42 (45.16 %) of the samples.
      The results of the present study showed that the water contamination with
      Acanthamoeba spp. in different regions of Isfahan can be a potential infection
      source for at high risk people. It could be suggested that public education and
      precaution are quiet necessary.

PMID- 27876972
TI  - Prevalence and seasonal variation of ectoparasites in cultured Nile tilapia
      Oreochromis niloticus in Saudi Arabia.
AB  - The prevalence, mean intensity and abundance of ectoparasites (monogeneans and
      trichodinids) from Nile tilapia Oreochromis niloticus were investigated during
      different seasons of two consecutive years, from January 2011 to December 2012. A
      total of 360 O. niloticus was collected from three fish farms located in the
      central region of Saudi Arabia. Prevalence, mean intensity and mean abundance of
      monogeneans on fish gills were found to be significantly (p < 0.01) higher in
      farm(C) (81.67, 495.23, 405.84 %) than farm (A) (7.5, 81.25, 8.34 %) and farm (B)
      (4.17, 62.5, 5 %) respectively. Similarly, the same parameters for trichodinids
      on gills were found to be significantly (p < 0.01) higher in farm (C) (97.5,
      97.5, 97.5 %), followed by farm (A) (39.17, 234.37, 35.00 %) and farm (B) (6.67,
      347.92, 30.00 %) respectively. The results of monogenean parameter on fish skin
      were found to be significantly (p < 0.01) higher in farm (C) (66.67, 443.68,
      294.16) followed by farm (A) (16.67, 124.58, 21.67 %) then farm (B) (0.83, 25,
      0.83 %) respectively. Similar results for trichodinid parameters on the skin were
      found to be higher (p < 0.01) in farm (C) (97.5, 875, 857.5 %), then farm (A)
      (26.67, 399.70, 215.01 %) and farm (B) (4.17, 154.17, 12.5 %) respectively. These
      results indicated that water quality and nutritional qualities were the major
      factors that affecting parasite occurrence, while the effect of temperature,
      seasonality and stocking density might have a secondary role on ectoparasite
      occurrence. Further studies should investigate that how the nutritional and water
      qualities affect the immunity of the fish to resist parasite infection.

PMID- 27876974
TI  - Mosquito larvicidal activity of cadmium nanoparticles synthesized from petal
      extracts of marigold (Tagetes sp.) and rose (Rosa sp.) flower.
AB  - Mosquitoes are blood-thirsty insects and serve as the most important vectors for
      spreading most notorious diseases such as malaria, yellow fever, dengue fever,
      and filariasis. The extensive use of synthetic mosquito repellent has resulted in
      resistance in mosquitoes. Therefore, the development of a reliable, eco-friendly
      processes for the synthesis of nano dimensional materials is an utmost important
      aspect of nanotechnology. In the present study, authors report absolute green
      synthesis of cadmium nanoparticles using marigold and rose flower petal extract.
      The characterization of nanomaterials was done by using UV-Vis, SEM, FTIR and
      fluorescent spectrophotometer analysis. Finally cadmium nanoparticles were also
      evaluated for their larvicidal activity of mosquito. Marigold flower petal
      extract shows 100 % mortality after 72 h of incubation with 10 ppm of Cd
      nanoparticles. No mortality was observed in the control. Therefore, out of two
      flower petal mediated nanoparticles, only marigold showed better performance
      towards mosquito larvicidal activity than rose petal extracts. This is the first
      report on mosquito larvicidal activity of flower-petal mediated cadmium
      nanoparticles. Thus, the use of marigold petal extract to synthesize cadmium
      nanoparticles is a rapid, ecofriendly, and a single-step approach and the CdNps
      formed can be potential mosquito larvicidal agents.

PMID- 27876973
TI  - Variation in lipid and fatty acid uptake among nematode and cestode parasites and
      their host, domestic fowl: host-parasite interaction.
AB  - Lipid synthesis is an important process in most organisms as well as in
      helminths. The present observation shows the variation of lipid and fatty acid
      uptake among cestode, Raillietina (Fuhrmannetta) echinobothrida; nematode,
      Ascaridia galli and their host, Gallus domesticus, the common country fowl. Total
      lipid (TL), neutral lipid (NL), glycolipid (GL), phospholipid (PL) and their
      fatty acid of cestode, nematode and liver and intestinal fluid of the host were
      analyzed by thin layer chromatography and gas liquid chromatography respectively.
      The result shows that liver take more TL, PL and GL except NL. Utilization of
      lipid from intestinal fluid when compare between the parasites, it is found that
      TL and PL content of cestode are higher than nematode, whereas, nematode absorbs
      more NL and GL than cestode. The percent of cholesterol is more in cestode than
      nematode. Palmitic, stearic, oleic and linoleic are the predominant fatty acids
      among all the samples. The present study reveals that the cestode having large
      surface area is more opportunistic in the resource utilization over the nematode
      as well as the host.

PMID- 27876975
TI  - Detection of Cryptosporidium spp. in free ranging animals of Tehran, Iran.
AB  - Cryptosporidium is a world widely distributed parasite which comparatively has a
      high prevalence in developing countries. The zoonotic potential of some
      Cryptosporidium species has made the cryptosporidiosis a significant concern to
      physicians and veterinarians. The occurrence and zoonotic potential of
      Cryptosporidium species in probable reservoir hosts for man infections was
      determined by examining faeces of symptomatic and asymptomatic animals. The aim
      of this study is to screen the presence of Cryptosporidium in fecal sample of
      free ranging animals in Tehran using Ziehl-Neelsen staining method. The findings
      indicate that Cryptosporidium are present in 9/50 (18 %) stray cat (Felis catus),
      12/50 (24 %) hooded crows (Corvus cornix), 23/180 (12.7 %) rat (Rattus norvegicus
      and R. rattus) and 1/40 (2.5 %) pigeons (Columba livia). This investigation
      confirms the potential role of rats, cats, crows and pigeons for zoonotic
      transmission of human cryptosporidiosis and they must be considered as reservoir
      hosts which can endanger public health.

PMID- 27876976
TI  - Variation in clinical markers in cattle naturally infected with bovine tropical
      theileriosis.
AB  - 124 cattle naturally infected with Theileria annulata were inspected for clinical
      markers. Clinical manifestations of general weakness, reduced appetite, pyrexia
      reaching 40-42  degrees C and lachrymal discharge were seen in more than 75 % of
      the infected animals. Presence of ticks on body, general dullness and depression,
      recumbency/prostration, oedema of dependent body parts, diarrhea,
      hypersalivation, pale mucous membranes and yellow colored urine were revealed by
      more than 50 % of the infected animals. Clinical manifestations of dehydration,
      abdominal distension/ascites, jaundice and haemoglobinuria were revealed by more
      than 25 % of the infected animals less than 25 % of the infected animals showed
      clinical manifestations of exophthalmia, constipation, melena, buccal cavity
      erosions, congested mucous membranes, nasal discharge and tachypnoea.

PMID- 27876977
TI  - A study on prevalence and identification of Ovine Theileria and Babesia infection
      in Zabol using PCR method.
AB  - Infection with Babesia and Theileria Causes high mortality and economical losses
      in livestock and has a relatively high prevalence in Iran. In Zabol, animals are
      susceptible to this disease because of presence of vector ticks, weather
      conditions and smuggle animal across the border and they cause great damages to
      the economy and production. However, few studies have been done for
      differentiation of Theileria and Babesia in sheep in this area. The purpose of
      the present study was to determine the prevalence of Babesiosis and Theileriosis
      in sheep in Zabol. A number of 80 animals were randomly selected and their blood
      samples were examined. The presence of Theileria and Babesia parasites in each
      sample was determined with PCR and microscopic examination. Of 80 blood samples
      obtained from sheep, 8 cases (10 %) were positive by microscopic examination
      where 6 samples were infected with Theileria and 2 samples with Babesia. The
      result of PCR method determined the prevalence of 66.25 % (53 samples) and 3.75 %
      (3 samples) for Theileria and Babesia, respectively. The correlation between
      these two methods (PCR and microscopic examination) was determined with Kappa
      statistical test. Based on the obtained results, it is concluded that Babesiosis
      has a low prevalence among the sheep of Zabol. This is the first report in which
      ovine Babesiosis has been studied in this region using molecular identification
      techniques.

PMID- 27876978
TI  - Parasitic infection alters haematology and immunity parameters of common carp,
      Cyprinus carpio, Linnaeus, 1758.
AB  - The present study was conducted to investigate the effects of parasite infection
      on haematological parameters of common carp, Cyprinus carpio. To this end, fish
      with same age were sampled from a warm water fish farm. After fish sampling, fish
      were transferred to lab for parasite study. Parasite incidence percent and
      density were calculated for two population carps. After parasite study, to
      investigate the haematological parameters, the blood sampling was carried out
      from two group fish i.e. infected (n = 20) and non-infected fish (n = 20).
      According our results, totally three parasite species were identified including
      Dactylogyrus sp., Trichodina sp. and Lernaea cyprinacea. Significant differences
      were observed between infected and non-infected fish (P < 0.05). In this regard,
      the values of haematocrit, haemoglobin and red blood cell were lower in infected
      fish than healthy individuals (P < 0.05). In contrast, number of white blood
      cells (WBCs) were higher in infected fish compared to non-infected fish (P <
      0.05). In conclusion, our study reveals that the parasite infection was
      responsible for altering the haematology of common carp. Increased number of WBC
      may be in relation to the defense mechanism and immunological responses against
      parasites.

PMID- 27876979
TI  - Seroprevalence of Toxoplasma gondii infection among childbearing age women in
      Kerman city, southeastern Iran.
AB  - This cross-sectional study aims to determine the prevalence of IgM and IgG anti
      T. gondii antibodies and the associated risk factors among childbearing age women
      referring to counseling centers before marriage in Kerman city, southeast of
      Iran. Totally, 300 serum samples were collected from women referred to Central
      Laboratory for Marriage Consultation in Kerman city were screened for IgG and IgM
      anti-T. gondii antibodies by enzyme linked immunosorbent assay (ELISA). Out of
      the 300 serum samples, 38 (12.6 %) tested seropositive for anti-T. gondii
      antibodies; 31 (10.3 %) samples tested seropositive for only IgG antibody, 1
      (0.33 %) tested seropositive for both IgM and IgG and 6 (2.0 %) were positive for
      IgM antibody alone. Statistical analyses also indicated that seroprevalence of
      anti-T. gondii antibodies increased with age (p < 0.05). Moreover, some risk
      factors such as, living in rural regions, contact with cats, raw/half-cooked meat
      consumption, and agricultural activities were significantly (p < 0.05) related to
      T. gondii seropositivity. The findings revealed that more than three-quarters of
      the childbearing age women studied in the present investigation are susceptible
      to infection during pregnancy. Thus, by adopting correct and improved practices
      we can improve their living conditions, and prevent infection and awareness and
      control of pathogens associated with disease is recommended.

PMID- 27876980
TI  - Prevalence of external parasites of pigeon in Zabol, southeast of Iran.
AB  - External parasites or ectoparasites, are arthropods that live on or in the skin
      or feathers, using the host as both shelter and food source. Ectoparasites can
      have significant impacts on animal health and productivity. The aim of this
      research was to estimate the prevalence and ectoparasites diversity in pigeons of
      Zabol, southeast of Iran. A total of 264 pigeons were selected randomly (175
      males and 89 females) to evaluate the presence of different ectoparasites.
      Ectoparasites were collected from different parts of the body and from walls and
      seams of cubbyholes, using hand lens, forceps, and flashlights to increasing the
      see sight. The samples were preserved in 70 % alcohol and cleared in lactophenol.
      The overall prevalence of external parasites in pigeon was 78.40 % [female (33.3
      %) and male (66.7 %)]. There was no significant difference of infestation of
      ectoparasites between male and female (P > 0.05). Prevalence was higher in adult
      pigeons (84.11 %) than pipers (54.0 %). Two species of ectoparasites were
      identified: Argas reflexus and Columbicola columbae.

PMID- 27876981
TI  - Detection of Fasciola hepatica and Fasciola gigantica common and uncommon
      antigens, using rabbit hyper immune serum raised against their excretory
      secretory and somatic antigens.
AB  - Fasciolosis is an important neglected helminth disease caused by two liver
      flukes, Fasciola hepatica and Fasciola gigantica. The two species of Fasciola are
      usually different in their morphological and molecular features. They have also
      common and uncommon antigens in both their somatic and excretory secretory
      metabolites. In this study, we compared somatic and excretory-secretory (ES)
      antigens of F. hepatica and F. gigantica, by using rabbit hyper immune serum
      raised against these antigens. Adult worms were collected from bile ducts of
      infected animals and species of the fluke was confirmed by RFLP-PCR. ES and
      somatic antigens of both species were prepared. Rabbits were subcutaneously
      immunized with either ES or somatic antigens to produce antibodies against these
      antigens. SDS-PAGE pattern of F. hepatica and F. gigantica somatic antigens was
      similar and both of them revealed 30 protein bands, ranging from 18 to 180 kDa.
      In contrast, SDS-PAGE pattern of ES antigen of the two species was different.
      While protein bands with molecular weight of 18, 27, 29, 48, and 62 kDa were
      common in both species, bands of 19, 45, 55 and 58 kDa were only noticed in F.
      hepatica ES antigen. Rabbit polyclonal antibodies, raised against F. hepatica and
      F. gigantica ES antigen, reacted with main five protein bands, 25, 27, 29, 62 and
      67 kDa and polyclonal antibodies raised against somatic antigens of both species
      reacted with three protein bands, 25, 27 and 72 kDa. Thus, the 25, 27 and 29 kDa
      protein bands may serve as immunodominant antigens, which might be considered for
      serodiagnosis of fasciolosis. Moreover, bands of 62 and 67 kDa in ES antigen and
      72 kDa in somatic antigens of both species were immunodominant and might be
      suitable candidate for development of serological assays for diagnosis of
      fasciolosis.

PMID- 27876982
TI  - Prevalence of Enterobius vermicularis infection among preschool children, Babol,
      North of Iran.
AB  - Enterobius vermicularis or pinworm, is considered as one of the most frequently
      encountered intestinal nematodes and infects millions of people throughout the
      world particularly children. Some symptoms of the infection including Anal
      itching, restlessness, insomnia, endometritis, abdominal cramps, diarrhea and
      etc. The purpose of the present study was to determine the status of enterobiasis
      in kindergarten and preschool children of kindergartens from Amir Kola, Babol
      Mazandaran Province, North of Iran. A total number of 126 (70 boys and 56 girls)
      children from four kindergartens from Amir Kola, Babol, Mazandaran Province,
      North of Iran were examined for the prevalence of E. vermicularis infection,
      2013. Adhesive cello-tape anal swab method was trained to parents for sampling.
      In addition, a questionnaire was designed and filled out to collect demographic
      information for each individual. Data were analyzed using Chi square test and
      multivariate logistic regression for each risk factor. The overall prevalence of
      E. vermicularis infection was 22.2 % (28). Infection with E. vermicularis in
      girls 23.2 % was higher compared to boys 21.4 %. Regarding age of examined
      individuals, infection was seen more both in boys and girls with the age of 6
      years old compared to other age groups. There was no significant difference
      between gender and age (p < 0.05). Based on the results of current study,
      prevalence of E. vermicularis in kindergarten and preschool children is high and
      still is an important public health matter in the north of Iran and should not be
      underestimated due to being highly contagious infection. Therefore, a systematic
      control and preventive measures should be adopted to reduce morbidity associated
      with enterobiasis.

PMID- 27876983
TI  - Macracanthorhynchus hirudinaceus: the most common helminthic infection of wild
      boars in southwestern Iran.
AB  - A pathological and epidemiological study on Macracanthorhynchus hirudinaceus
      infection on 25 wild boars Sus scrofa in southwestern Iran was done. Overall 24
      helminthes (18 female and 6 male) were collected from the intestine of 13
      infected wild boars. Thus, the prevalence of acanthocephalans among the 25
      examined boars was 52 %. Pathological evaluation revealed damages caused by the
      acanthocephalans penetrated in the small intestine tissue. Helminthes caused
      severe necrosis with ulcer and inflammation in tunica sub mucosa layer. High
      prevalence of this helminthic infection may cause severe hazard for farmers,
      residents and also wild life animals.

PMID- 27876984
TI  - First serological study of equine hydatidosis in Iran.
AB  - Hydatidosis, is an important worldwide zoonotic disease caused by larval stages
      (metacestodes) of tapeworm parasites of the genus Echinococcus. The objective of
      the present study was to determine the seroprevalence of equine hydatidosis in
      Iran by latex agglutination test. This study also served to correlate sex and age
      with mentioned results in cases. Therefore, 193 serum samples were collected from
      clinically healthy horses at 9 race clubs in Kerman, Yazd and Golestan provinces,
      Iran. According to the results, antibodies against hydatidosis were detected in 6
      sera (3.11 %) among 193 samples. Results showed two male and four female horses
      were sero-positive against hydatidosis. In conclusion, present study shows that
      antibodies against hydatidosis have been detected in Iran equine population.
      Therefore, it seems that Iranian horse clubs should improve their management and
      health levels to increase their proficiencies.

PMID- 27876985
TI  - In vitro anti-leishmanial activity of Satureja hortensis and Artemisia
      dracunculus extracts on Leishmania major promastigotes.
AB  - Cutaneous leishmaniasis is one of the important skin diseases with diverse
      clinical manifestations. With an incidence of 0.7-1.3 million cases annually,
      this disease is often reported from six countries, including Iran. Accordingly,
      the purpose of this study was to evaluate the anti-leishmanial effect of the
      three plant hydroalcoholic extracts including fleawort (Plantago psyllium L.),
      savory (Satureja hortensis L.) and tarragon (Artemisia dracunculus L.) on
      Leishmania major promastigotes. The hydroalcoholic extract from each plant was
      extracted and its anti-leishmanial effect was evaluated in different
      concentrations (100-1000 ug/ml) and at various hours (24, 48 and 72 h). Savory
      herb inhibitory concentration 50 % (IC50) at 24, 48 and 72 h was 790.81, 398.11
      and 298.42 ug/ml, respectively. In addition, tarragon herb IC50 at 24, 48 and 72
      h was 962.03, 688.36 and 585.51 ug/ml, respectively. Moreover, the fleawort
      extract was showed the lowest effect, considering that its effect at the
      concentration of 1000 ug/ml was 48 % after 72 h (P > 0.05). Furthermore, the
      statistical analysis showed a significant difference for interaction between
      concentration and time regarding the tarragon and savory extracts with a P value
      of lower than 0.05. According to the results, the anti-leishmanial effect of the
      tarragon and savory extracts may make it possible to use them in the treatment of
      cutaneous leishmaniasis as a complementary or alternative therapy; however,
      further studies are necessary and should be evaluated in cell culture and in vivo
      conditions to confirm it.

PMID- 27876986
TI  - Prevalence and pathological lesions of ovine cysticercosis in slaughtered sheep
      in western Iran.
AB  - Cysticercusovis, the intermediate stage of a canine tapeworm, Taenia ovis,
      produces cystic lesions in the skeletal and cardiac muscle of sheep which, if
      numerous, will result in the condemnation of an entire carcass. This study was
      carried out between March 2013 and March 2014 to estimate the prevalence of
      Taenia oviscysticercosis in sheep slaughtered at the Kermanshah municipal
      abattoir, in western Iran. Of 69,198 sheep examined, 833 (1.27 %) were infected
      with cysticerci of Taenia ovis. The prevalence of C. ovis was significantly
      higher in males than females (P < 0.05). Seasonal analysis revealed significantly
      higher prevalence in spring (1.8 %) than other seasons (P < 0.005). The heart
      muscles (29.7 %), diaphragm (18.8 %), masseter muscles (18.2 %) and tongue (15.5
      %) were the main predilection sites of the cysts. The cysts of ovinecysticercosis
      were also identified on the triceps, intercostal muscles, thigh muscles,
      intestinal mucosa, liver and Spleen. This parasite caused extensive damage
      resulting in infiltrative, degenerative changes, necrosis and exudation mainly in
      the vicinity of cysts. The results indicate that the prevalence of C. ovis in
      this area is high. Therefore improving the standard of disease prevention and
      control on farms is necessary.

PMID- 27876987
TI  - Prevalence of hypodermosis in cattle slaughtered in industrial slaughtered-house
      of Ardebil, Iran.
AB  - Hypodermosis is one of the important veterinary problems because of its worldwide
      prevalence and significant economic losses. Economic losses is due to decreasing
      of productivity potential and leather quality. The disease is caused by two
      parasitic fly species in cattle, Hypoderma bovis and lineatus. Diagnosis of the
      parasites has crucial importance because of treatment and eradication plannings.
      Basically diagnosis is based on parasitological methods but recently serological
      methods were used in some countries. In the present study, a total of 3716 cattle
      were investigated in Industrial Slaughter house of Ardebil, Northwest of Iran. In
      this study, the prevalence of H. lineatus and H. bovis was 0.32 % (12 larva) and
      1.07 % (40 larva), respectively. Low prevalence of hypodermosis could be caused
      by cold climate of studied region also shows efficacy of controlling programs.
      Unlike low prevalence of Hypoderma spp. in the studied regions, antiparasitic
      agents such as organophosphates and avermectins should be used to reduce the
      prevalence.

PMID- 27876988
TI  - Cryptosporidiosis in a buffalo calf at Meerut, Uttar Pradesh and its successful
      therapeutic management.
AB  - Cryptosporidium spp. are recognized as one of the most important enteric
      pathogens causing enteritis and severe diarrhoea in calves up to 1 month of age.
      Although the infection may be responsible for some mortality, its impact is
      mainly associated with the impairment of gastrointestinal functions and lower
      performance of animals. A female buffalo calf of 25 days old was presented to OPD
      section, College of Veterinary and Animal Sciences, SVPUA&T, Meerut, with the
      symptoms of severe voluminous watery cholera like diarrhea with mucous and blood
      tinge since 4-5 days. On physical examination, calf was dehydrated, weak, and
      emaciated with normal temperature. Parasitological examination of the faeces by
      the direct smear and modified Ziehl-Neelsen staining technique revealed presence
      of high number of Cryptosporidium spp. oocysts. The affected female buffalo calf
      was treated with azithromycin and provided supportive care. Diarrohoeal symptoms
      were stopped from 3rd day and animal returned to normal condition by 7th day post
      treatment.

PMID- 27876989
TI  - Seroprevalence of toxoplasmosis in diabetic pregnant women in southwestern of
      Iran.
AB  - To investigate anti-Toxoplasma gondii IgG and IgM antibodies in diabetic pregnant
      women in Ahvaz, southwest of Iran this experiment was performed. In current study
      the sera of 110 diabetic pregnant women as well as 110 non diabetic pregnant
      women referred to the hospitals affiliated with the Ahvaz Jundishapur University
      of Medical Sciences were assessed for anti-T. gondii IgG and IgM antibodies by
      ELISA and IFA methods. The ELISA assessments showed that 47 (42.7 %) and 3 (2.7
      %) of diabetic women were positive for IgG and IgM antibodies, respectively.
      However, in the control group, 24 individuals (21.81 %) were positive for IgG
      antibody but no detection for IgM antibody. According to IFA method, 46 (41.8 %)
      and 3 (2.7 %) of diabetic women were positive for IgG and IgM antibodies,
      respectively, while in control group, 21 individuals (19.09 %) were positive for
      IgG antibody. In this method, IgM antibody was negative for all samples of
      control group (0 %). In both methods, the values obtained in the case group were
      significantly higher than those in the control group (p < 0.05). Prevalence of
      anti-Toxoplasma IgG and IgM antibodies in diabetic pregnant women was higher than
      that in non-diabetic pregnant women. It seems that screening tests for seeking
      patients and teaching the transmission routes should be considered as prenatal
      cares for diabetic women.

PMID- 27876990
TI  - Comparative in vitro anti-tick efficacy of commercially available products and
      newly developed phyto-formulations against field collected and resistant tick
      lines of Rhipicephalus (Boophilus) microplus.
AB  - Rhipicephalus (Boophilus) microplus is considered as one of the most widely
      distributed tick species ecto-parasitizing on livestock and causes fatal diseases
      with significant production loss. To address the problem of controlling acaricide
      resistant tick infestations on animals, attention has been paid to develop eco
      friendly phyto-acaricides. The present study was undertaken to evaluate the
      comparative anti-tick activities of commercially available herbal and chemical
      products with chemically characterized phyto-formulations developed recently
      against field ticks and resistant tick lines of R. (B.) microplus. The chemical
      product Butox(r) Vet was found nearly passive against all the tested resistant
      tick lines. However, one of the commercial polyherbal product, Zerokeet(r) showed
      an efficacy (E%) of 41.8-75.4 % ([Formula: see text]) using recommended dilution
      (1:2) against field ticks and resistant tick lines. However, the other commercial
      product, Erina(r) EP has very limited efficacy against all the tested tick. In
      comparison, the newly developed phyto-formulation, NBA/13/B/2 and NAC-01
      conferred an E% of 82.4-91.3 % ([Formula: see text]) and 62.3-94.6 % ([Formula:
      see text]), respectively, against tested resistant ticks. Results indicated
      higher marketing potentiality of newly developed formulation in the existing tick
      problem scenario.

PMID- 27876991
TI  - Trichomoniasis in older individuals: a preliminary report from Iran.
AB  - Infection with Trichomonas vaginalis is one of the most common sexually
      transmitted diseases (STDs) in humans. The prevalence of infection in Iran has
      been reported 0.009-8 % depending on deferent socio-cultural conditions. This
      study aimed to determine the frequency of T. vaginalis according to age in
      patients referred to clinics, hospitals and medical diagnostic laboratories in
      Karaj city, Iran. For this purpose, fifty positive samples were collected from
      July 2012 to June 2014 from clinics, medical diagnostic laboratories and
      hospitals, then transferred to laboratory of parasitology and cultured in TYM
      medium. The results showed that all isolates were successfully cultured. Among 50
      positive specimens, 43 cases were female and 7 cases male. The most positive
      cases (34 %) belonged to the ages over 50 year's group. The lowest positive cases
      (2 %) belonged to the ages of less than 20 years group. In Conclusion, unlike
      other STDs, which have a higher prevalence among adolescents and young adults,
      the rates of trichomoniasis are more evenly distributed among sexually active
      women of all age groups. However, frequency of this infection in women aged over
      50 years (age of menopause) is notable and complementary studies are needed.

PMID- 27876992
TI  - Traditional versus molecular based detection of a rare occurrence of babesiosis
      in Gir calf and its therapeutic management.
AB  - A 30-day old Gir calf was brought to Veterinary Polyclinic with symptoms of high
      fever, dullness, dyspnea, pale mucus membrane and haemoglobinuria. Blood sample
      was collected and microscopic examination of thin blood smear confirmed the case
      of acute babesiosis. It was further confirmed by polymerase chain reaction that
      amplified an approximately 410 bp portion of the ssu-rDNA of Babesia spp. The
      calf was managed with diminazene aceturate @5 mg/kg (Berenil) intramuscularly
      followed by supportive therapy including intravenous infusions. The present study
      reports a rare case of bovine babesiosis, its clinical variants, diagnosis,
      hematology and therapeutic management.

PMID- 27876993
TI  - A unique case of Babesia gibsoni infected dog with paraplegia.
AB  - A 4 year old male Rottweiler was presented to Teaching Veterinary Clinics of
      GADVASU with a primary complaint of paraplegia, fever and inappetence. The dog
      was found to be dull with elevated rectal temperature (105  degrees F), heart
      rate (158 per minute) and respiration rate (57 per minute). Blood smear
      examination and PCR assay revealed that dog was positive for Babesia gibsoni.
      Elevated bilirubin, alanine aminotransferase, alkaline phosphatase, creatinine,
      total leucocyte count, neutrophils and hypoglycaemia were haemato-biochemical
      alterations. The therapy targeting babesiosis was carried out with a single dose
      of diminazene aceturate in combination with doxycycline, enrofloxacin and
      metronidazole for 21 days. Complete follow up of the case revealed complete
      clinical recovery within 21 days.

PMID- 27876994
TI  - Epidemiological trend of cutaneous leishmaniasis in two endemic focus of disease,
      south of Iran.
AB  - Cutaneous leishmaniasis is one the most important zoonotic diseases has different
      invertebrate hosts in different parts of its range, the vectors are often closely
      related. Leishmaniasis is a world-wide vector borne disease, affecting 88
      countries: especially in the Middle East and southwestern Asia. Nesokiaindica or
      M. libycuserythrourus are confirmed as reservoir and Phlebotomine sand flies are
      proven as vectors of the disease in the south of Iran. Patients' information
      collected from Firouzabad and Ghirokarzin county, Fars province in Iran during
      2006-2014. Data analyzed by Chi square test using SPSS19 statistic software. 613
      cases (61.91 %) lived in rural and 377 (38.08 %) lived in urban areas. All ages
      were grouped between 1 and >=30 years. 479 (48.38 %) of patients being male and
      511 (51.61 %) female. 39.49 % of patients were with dry lesions and 60.5 % were
      with wet lesions. Hand ulcers were the highest prevalence part of body (39.59 %).
      The common frequent size of lesions was lesser than 2 cm. Regarding the most
      prevalence rate (47.67 %) raised in autumn season. This study showed that
      cutaneous leishmaniasis was an endemic disease in Firouzabad and Ghirokarzin
      regions.

PMID- 27876995
TI  - Two new species of xiphidiocercariae from the apple snail Pila virens in Malabar,
      Kerala.
AB  - Two new species of xiphidiocercariae, Cercaria sp. XIV Malabar n. sp. and
      Cercaria sp. XV Malabar n. sp. were recovered from the apple snail Pila virens
      collected from freshwater bodies in the Malabar region of Kerala. Cercaria sp.
      XIV Malabar n. sp. was recovered from P. virens collected from Modakkallur in
      Kozhikode district and Cercaria sp. XV Malabar n. sp. from the same snail species
      collected from Payyanur in Kannur district. Sporocysts were also recovered from
      the infected snail hosts. The two new species of cercariae are described in
      detail and compared with related species to establish their systematic position.

PMID- 27876996
TI  - New data about the helminth fauna of the red squirrel (Sciurus vulgaris Linnaeus,
      1758) in Belorussian Polesie.
AB  - The result of helminthological examination of 5 red squirrels in Belorussian
      Polesie during 2003-2012 is presented. Two species of helminths were found:
      Taenia martis (Zeder, 1803) larvae and Syphacia thompsoni Price, 1928. The red
      squirrel for the first time established as host of cestode T. martis. The
      nematode S. thompsoni registered as Syphacia sp. in this region between 1985 and
      2000.

PMID- 27876997
TI  - Scope of detectability of circulating antigens of human lymphatic filarial
      parasite Wuchereria bancrofti with smaller amount of serum by Og4C3 assay: its
      application in lymphatic filariasis elimination programme.
AB  - Filarial antigen detection is an appropriate epidemiological indicator for
      mapping lymphatic filariasis and impact evaluation of filariasis elimination
      programme in view of low sensitivity of parasite detection. Monoclonal antibody
      based Og4C3 immunological test requires 100 ul serum, which is difficult to
      collect by finger prick method during community based surveys. Hence, we tested
      lesser volume of serum compared to standard volume of 100 ul to compare its
      sensitivity and specificity in detecting the circulating filarial antigens. Blood
      samples were collected from individuals who tested positive [with titer groups 4
      (border line positives), 6 (medium positives), and 8 (high positives)] and
      negative (titre group 3) for Og4C3 assay. Different volumes of serum samples were
      used to make-up required volume (100 ul) with appropriate dilutions and subjected
      to Og4C3 assay. The results showed that known negative samples tested negative at
      all the serum volumes tested. All positives (titer groups 6 and 8) showed
      positivity at all reduced volumes of serum sample. However one of the medium
      positive sample showed negative reaction in 5 ul volume of serum and two of the
      border line positives showed negative at all the serum volume tested. The results
      thus showed as less as 15 ul serum is adequate for use in Og4C3 assay. So the
      test can be performed without losing its sensitivity even with 5 ul serum samples
      at high titre of antigen (titre group 8) and 15 ul for other groups and this
      method has scope in programme evaluation.

PMID- 27876998
TI  - Occurrence of Knemidokoptes mutans and Laminosioptes cysticola in backyard
      poultry in India.
AB  - Birds reared in backyard poultry farming system are more prone to parasitic
      infestation resulting in economic losses to rural community. The present study
      reports occurrence of Knemidokoptes mutans and Laminosioptes cysticola mites in a
      male Aseel bird. Clinical signs observed in the affected bird include
      hyperkeratosis with whitish film layer on shank and hock region of legs. Focal
      areas of sloughing of skin with oozing of blood were also observed on the back
      and on the legs. Examination of skin scrapings from the affected sites revealed
      different developmental stages of Knemidokoptes mutans and Laminosioptes
      cysticola mites. This paper reports occurrence of L. cysticola for the first time
      from India. The bird was treated with ivermectin injection through intramuscular
      route.

PMID- 27876999
TI  - Outbreak of Notozothecium bethae (Monogenea: Dactylogyridae) in Myleus
      schomburgkii (Actinopterygii: Characiformes) cultured in the Peruvian Amazon.
AB  - The presence of Notozothecium bethae was investigated in 76 black band myleus
      (Myleus schomburgkii [Actinopterygii: Charasiformes]) born and kept in captivity
      in two semi-intensive breeding cages in the northern region of Peru. Among the 76
      cultivated specimens of M. schomburgkii examined in the present study, 100 % had
      monogenean on the gill and the parasites were identified as Notozothecium bethae.
      During the survey no bacteria was isolated, and no protozoan or other metazoan
      parasites were found. The prevalence of N. bethae remained constant throughout
      the present study. Mean intensity of N. bethae in the months of April and May was
      exceptionally high in both facilities. The massive infection of N. bethae on the
      gills of M. schomburgkii was associated with mortality. This is the first report
      of N. bethae in M. schomburgkii born in captivity and cultured in the Amazon
      region. The mortality due the presence of this parasite emphasise the need for
      disease control strategies of cultured M. schomburgkii.

PMID- 27877001
TI  - RETRACTED ARTICLE: Evaluation of intestinal parasites among referred patients:
      report of 4637 cases.

PMID- 27877000
TI  - Psychiatric aspects of toxoplasmosis: an Indian perspective.
AB  - Toxoplasma gondii is one of the well-studied parasites because of its medical and
      veterinary importance, and its suitability as a model for cell biology and
      molecular studies. Latent toxoplasmosis in an immunocompetent host was considered
      benign until recently. The importance of this parasite has been steadily rising
      in the field of psychiatry and neurology as it has been implicated in numerous
      neuropsychiatric disorders. Researchers in India have unfortunately restricted
      themselves to finding the prevalence of toxoplasma antibodies in special
      populations and animals. On the other hand, there has been increasing research
      interest worldwide in T. gondii for its effects on human behaviour,
      manifestations of which range from psychoses and neuroses to Alzheimer's and
      Parkinson's disease. Toxoplasma infected organisms may be akin to living zombies.
      From changing the core natural defensive behaviour in mice to changing
      personality & leading to neuropsychiatric disorders in humans, Toxoplasma brings
      about subtle but significant & specific changes in its host. Surprisingly there
      is severe dearth of such studies from India even though prevalence rates of
      latent Toxoplasma infection are comparable, or in some regions, higher to those
      found elsewhere in the world. The potential for identifying Toxoplasma induced
      behavioural alterations is enormous in this part of the world which could have
      future treatment implications. It's high time that we move beyond researching the
      obvious and involve ourselves in more rigorous, novel and stimulating studies in
      the future.

PMID- 27877002
TI  - RETRACTED ARTICLE: Frequency of intestinal protozoan parasites in patients with
      gastrointestinal disorders in south of Karaj, Iran.

PMID- 27877003
TI  - Retraction Note to: Prevalence of ixodid ticks on cattle and sheep northeast of
      Iran.
AB  - [This retracts the article DOI: 10.1007/s12639-014-0576-6.].

PMID- 27877004
TI  - Retraction Note to: Histopathological features of cutaneous and gastric
      habronemiasis in horse.
AB  - [This retracts the article DOI: 10.1007/s12639-014-0611-7.].

PMID- 27877005
TI  - Revalidation of a prognostic score model based on complete blood count for
      nasopharyngeal carcinoma through a prospective study.
AB  - OBJECTIVE: In our previous work, we incorporated complete blood count (CBC) into
      TNM stage to develop a new prognostic score model, which was validated to improve
      prediction efficiency of TNM stage for nasopharyngeal carcinoma (NPC). The
      purpose of this study was to revalidate the accuracy of the model, and its
      superiority to TNM stage, through data from a prospective study. METHODS: CBC of
      249 eligible patients from the 863 Program No. 2006AA02Z4B4 was evaluated.
      Prognostic index (PI) of each patient was calculated according to the score
      model. Then they were divided by the PI into three categories: the low-,
      intermediate-and high-risk patients. The 5-year disease-specific survival (DSS)
      of the three categories was compared by a log-rank test. The model and TNM stage
      (7th edition) were compared on efficiency for predicting the 5-year DSS, through
      comparison of the area under curve (AUC) of their receiver-operating
      characteristic curves. RESULTS: The 5-year DSS of the low-, intermediate-and high
      risk patients were 96.0%, 79.1% and 62.2%, respectively. The low-and intermediate
      risk patients had better DSS than the high-risk patients (P<0.001 and P<0.005,
      respectively). And there was a trend of better DSS in the low-risk patients,
      compared with the intermediate-risk patients (P=0.049). The AUC of the model was
      larger than that of TNM stage (0.726 vs. 0.661, P=0.023). CONCLUSIONS: A CBC
      based prognostic score model was revalidated to be accurate and superior to TNM
      stage on predicting 5-year DSS of NPC.

PMID- 27877006
TI  - Early prediction of pathological outcomes to neoadjuvant chemotherapy in breast
      cancer patients using automated breast ultrasound.
AB  - OBJECTIVE: Early assessment of response to neoadjuvant chemotherapy (NAC) for
      breast cancer allows therapy to be individualized. The optimal assessment method
      has not been established. We investigated the accuracy of automated breast
      ultrasound (ABUS) to predict pathological outcomes after NAC. METHODS: A total of
      290 breast cancer patients were eligible for this study. Tumor response after 2
      cycles of chemotherapy was assessed using the product change of two largest
      perpendicular diameters (PC) or the longest diameter change (LDC). PC and LDC
      were analyzed on the axial and the coronal planes respectively. Receiver
      operating characteristic (ROC) curves were used to evaluate overall performance
      of the prediction methods. Youden's indexes were calculated to select the optimal
      cut-off value for each method. Sensitivity, specificity, positive and negative
      predictive values (PPV and NPV) and the area under the ROC curve (AUC) were
      calculated accordingly. RESULTS: ypT0/is was achieved in 42 patients (14.5%)
      while ypT0 was achieved in 30 patients (10.3%) after NAC. All four prediction
      methods (PC on axial planes, LDC on axial planes, PC on coronal planes and LDC on
      coronal planes) displayed high AUCs (all>0.82), with the highest of 0.89 [95%
      confidence interval (95% CI), 0.83-0.95] when mid-treatment ABUS was used to
      predict final pathological complete remission (pCR). High sensitivities (85.7%
      88.1%) were observed across all four prediction methods while high specificities
      (81.5%-85.1%) were observed in two methods used PC. The optimal cut-off values
      defined by our data replicate the WHO and the RECIST criteria. Lower AUCs were
      observed when mid-treatment ABUS was used to predict poor pathological outcomes.
      CONCLUSIONS: ABUS is a useful tool in early evaluation of pCR after NAC while
      less reliable when predicting poor pathological outcomes.

PMID- 27877007
TI  - Further understanding of an uncommon disease of combined small cell lung cancer:
      clinical features and prognostic factors of 114 cases.
AB  - OBJECTIVE: Combined small cell lung cancer (C-SCLC) is an uncommon subgroup of
      small cell lung cancer (SCLC) and few clinical data can be referred. Our study is
      to investigate the clinical features and prognostic factors of C-SCLC, as well as
      the role of multimodality treatment. METHODS: Between January 2004 and December
      2012, patients with histologically diagnosed C-SCLC were retrospectively
      analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate
      and multivariate analyses were used to evaluate potential prognostic factors.
      RESULTS: One hundred and fourteen patients were enrolled, with a median age of 59
      (range: 20-79) years old. The most common combined component was squamous cell
      carcinoma (52.6%). Among these patients, the disease was stage I, II, III and IV
      in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients
      (70.2%) received at least two of the three modalities containing chemotherapy,
      radiotherapy and surgery. The median follow-up was 32.5 months. The median time
      of overall survival (OS) was 26.2 months. On univariate analysis, smoking
      (P=0.029), Karnofsky performance score (KPS) <80 (P=0.000), advanced TNM stage
      (P=0.000), no surgery (P=0.010), positive resection margin (P=0.000), positive
      lymph nodes >=4 (P=0.000), positive lymph node ratio >10% (P=0.000) and non
      multimodality treatment (P=0.004) were associated with poor OS. Multivariate
      analysis confirmed that smoking, advanced TNM stage, positive resection margin
      and positive lymph nodes ratio >10% were poor prognostic features. CONCLUSIONS: C
      SCLC has a relatively early stage and good prognosis, which may due to the
      underestimated diagnosis in non-surgical patients. Multimodality therapy is
      recommended, especially for limited disease. Smoking, advanced TNM stage,
      positive resection margin and positive lymph nodes ratio >10% are poor prognostic
      factors.

PMID- 27877008
TI  - Detection of ALK translocation in non-small cell lung carcinoma (NSCLC) and its
      clinicopathological significance using the Ventana immunohistochemical staining
      method: a single-center large-scale investigation of 1, 504 Chinese Han patients.
AB  - OBJECTIVE: The novel fully automated immunohistochemistry (IHC) assay-Ventana
      anaplastic lymphoma kinase (ALK)-D5F3 for screening ALK rearrangements has been
      approved by China's Food and Drug Administration in 2013, our previous study
      disclosed a highly specificity and sensitivity nearly 100%, and its efficacy
      needs to be evaluated in a large cohort of primary lung adenocarcinoma patients,
      and to compare clinicopathological features with ALK (+) and ALK (-) lung
      adenocarcinoma. METHODS: A total of 1,504 consecutive surgical lung
      adenocarcinoma cases of Chinese Han population were collected and re-diagnosed
      according to the 2011 multidisciplinary classification of lung adenocarcinoma.
      Fully automated Ventana ALK-D5F3 IHC staining with a binary scoring was adopted
      to evaluate staining and correlated with clinicopathological characters,
      including age, sex, differentiation degree, histological subtype, lymph node
      metastasis, and clinical staging. ALK (+) patients were followed-up, and targeted
      therapy of ALK-inhibitors was adopted and observed in patients with stage IV
      according to the NCCN guideline. RESULTS: ALK positive adenocarcinomas were
      identified in 6.6% of the surgically resected 1,504 NSCLCs, and significantly
      younger than the negative group (P<0.05).Mucinous adenocarcinoma (28.2%) was
      determined to be predominant in ALK (+) cases, followed by the solid type
      (11.7%), specific type (6.8%), papillary type (5.6%), acinar type (5.5%), and
      lepidic type (3.1%), and the differences were statistically significant
      (chi2=42.011, P<0.05). ALK (+) adenocarcinoma with lymph node metastasis (10.8%)
      were significantly higher than that without lymph node metastasis (4.5%)
      (chi2=19.809, P<0.05); and ALK (+) in phase IV (20%) was significantly higher
      than phase III (12.9%), phase II (4.2%), phase I (4.5%), and phase 0 (0)
      (chi2=36.068, P<0.05). Multivariate logistic regression disclosed that patient
      age, AJCC staging, and histological mucinous subtype were correlated with ALK
      positive staining (OR=0.959, 1.578, 5.036, respectively). Sixty eight patients
      had followed-up results, five patients out of which primarily diagnosed or
      progressed into Stage IV benefited well from targeted therapy with Crizotinib.
      CONCLUSIONS: The ALK fusion protein was seen in 6.6% Chinese NSCLC patients, and
      mostly seen in younger, clinically higher staging, mucinous and solid predominant
      adenocarcinoma. Clinical trials in patients of Stage IV confirmed that ALK-D5F3
      Ventana IHC is serviceable in screening ALK-positive candidates for molecular
      targeted therapy.

PMID- 27877009
TI  - Characteristics of gastric cancer recurrence five or more years after curative
      gastrectomy.
AB  - OBJECTIVE: To investigate the characteristics of recurrences that occurred 5 or
      more years after curative resection for gastric cancer. METHODS: We analyzed
      recurrences among 1,299 patients with gastric cancer who underwent curative
      operations at the Department of Surgery, Inje University Seoul Paik Hospital
      between September 1998 and December 2002. Recurrences were classified as within 2
      years (early), 2-5 years (intermediate), and more than 5 years (late) after
      gastrectomy. The clinicopathologic findings of the patients with late recurrence
      were compared with those of patients in the other two recurrence groups, with
      special reference to the patterns of recurrence. Both univariate and multivariate
      analyses were performed, incorporating factors such as operation type, T-stage, N
      stage, stage, lymphatic invasion, neural invasion, histology, tumor size, and
      recurrence site. RESULTS: At the time of last follow-up, recurrence occurred in
      266 (20.5%) patients. Recurrence times were classified as <2 years (182
      patients), 2-5 years (61 patients), or >5 years (23 patients). The late
      recurrence rate was 8.6%. The occurrence of recurrence >5 years after gastrectomy
      was significantly correlated with age, operation type, T-stage, N-stage, stage,
      lymphatic invasion, neural invasion, histology, tumor size, location and
      recurrence site (P<0.05). The main recurrence patterns in the 23 patients with
      late recurrence were locoregional metastasis (10 patients, 43.5%), peritoneal
      seeding (8 patients, 34.8%), hematogenous metastasis (2 patients, 8.7%), and
      multiple metastasis (3 patients, 13.0%). A multivariate analysis showed that
      larger tumor size and younger age were independent prognostic factors for late
      recurrence. Additionally, locoregional and peritoneal recurrences were
      significantly more common than hematogenous recurrences. CONCLUSIONS: Although
      late recurrence was uncommon, younger age and larger tumor size were associated
      with high risk. Follow-up surveillance is recommended for locoregional and
      peritoneal metastasis.

PMID- 27877010
TI  - Comparison of lymph node number and prognosis in gastric cancer patients with
      perigastric lymph nodes retrieved by surgeons and pathologists.
AB  - OBJECTIVE: To compare the numbers of positive and total lymph nodes and prognosis
      in gastric cancer patients whose perigastric lymph node retrieval was performed
      by surgeons and pathologists. METHODS: We conducted a retrospective analysis of
      clinical and follow-up data from 1, 056 patients who underwent gastric cancer D2
      radical lymph node resection between January 2008 and December 2010 in the
      Gastrointestinal Surgery Department of Yantai Yuhuangding Hospital. The follow-up
      ended in December 2015. Patients were divided into two groups according to the
      specialty of physicians who performed the postoperative perigastric lymph node
      retrieval: the surgeon group (475 cases) and the pathologist group (581 cases).
      The numbers of positive and total perigastric lymph nodes and the 3- and 5-year
      survival were compared between gastric cancer patients in the two groups overall
      and stratified by TNM stage (the 7th Edition of the American Joint Committee on
      Cancer). RESULTS: Overall, the numbers of positive and total lymph nodes were
      significantly higher in the surgeon group than in the pathologist group (6.53+/
      4.07 vs. 4.09+/-3.70, P=0.021; 29.64+/-11.50 vs. 20.71+/-8.56, P<0.001). Further
      analysis showed that the total number of lymph nodes in stage I patients (19.40+/
      9.62 vs. 15.45+/-8.59, P=0.011) and the numbers of positive and total lymph nodes
      in stage II (1.38+/-1.08 vs. 0.87+/-1.55, P=0.031; 25.35+/-10.80 vs. 16.75+/
      8.56, P<0.001) and stage III patients (8.11+/-6.91 vs. 6.66+/-5.12, P=0.026;
      32.34+/-12.55 vs. 25.45+/-8.31, P<0.001) were significantly higher in the surgeon
      group than in the pathologist group. The survival analysis showed that the 3- and
      5-year survival of stage II and III patients was significantly higher in the
      surgeon group than in the pathologist group (82.0% vs. 73.1%, 69.5% vs. 61.2%,
      P=0.038; 49.2% vs. 38.9%, 36.3% vs. 28.0%; P=0.045). CONCLUSIONS: Compared with
      retrieval performed by pathologists, postoperative perigastric lymph node
      retrieval performed by surgeons was associated with significant increase in the
      total lymph node number of stage I patients, the numbers of positive and total
      lymph nodes of stage II and III patients, and the survival of stage II and stage
      III gastric cancer patients.

PMID- 27877011
TI  - Analysis of clinical characteristics and treatment of pancreatic cystic tumors.
AB  - OBJECTIVE: To summarize experience in the diagnosis and treatment of pancreatic
      cystic neoplasms. METHODS: This is a retrospective study of 207 patients who were
      diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital
      between Jan 2009 and Mar 2014. Clinical data, such as clinical manifestations,
      radiological and pathological images and surgical recordings, were collected.
      RESULTS: Of the 207 included patients, females accounted for 76.81%, and the mean
      patient age was 52.04 years. Malignancy was more common in older patients who
      presented with marasmus and jaundice. Other risk factors included solid
      components in the tumor, a large tumor size, and elevated levels of tumor
      markers. Surgical treatment was required when a malignant tumor was suspected.
      The operation approach was selected based on the location, size and
      characteristics of the tumor. The position of the tumor relative to the
      pancreatic duct also played a significant role. CONCLUSIONS: No specific symptoms
      were observed for the patients with pancreatic cystic tumors. Imaging played an
      important role in making a differential diagnosis. Furthermore, surgical
      treatment should be proposed for patients with significant symptoms and
      potentially malignant tumors. The tumor resection rate is high, suggestive of
      good prognosis.

PMID- 27877012
TI  - Simultaneous hepatic resection benefits patients with synchronous colorectal
      cancer liver metastases.
AB  - OBJECTIVE: The safety of the simultaneous resection of synchronous colorectal
      cancer liver metastases (SCRLM) is still being debated. However, this
      simultaneous operative approach is more commonly adopted at present than in the
      past. Therefore, we compared simultaneous hepatic resection with delayed hepatic
      resection in this study. METHODS: All patients with SCRLM diagnosed before
      initial treatment between January 2009 and September 2013 were retrospectively
      included in our study. Short-term and long-term outcomes were compared in
      patients who underwent simultaneous colorectal and hepatic resection and those
      treated by delayed hepatectomy. RESULTS: Among the 73 patients diagnosed with
      SCRLM, simultaneous colorectal and hepatic resection was performed in 60 patients
      (82.2%), while delayed hepatic resection was performed in 13 patients (17.8%).
      The mortality rate was zero. The postoperative complication rate after delayed
      resection was higher than, but not significantly different from, that after
      simultaneous resection (46% vs. 23%, P=0.166). The duration of operating time
      (240 vs. 420 min, P<0.05) and postoperative hospital stay time (11 vs. 18 days,
      P<0.05) were shorter in the simultaneous resection group. After the initial
      treatments were given, the 1-, 2-, and 3-year survival rates in the simultaneous
      resection group were 77%, 59%, and 53%, respectively, whereas those in the
      delayed resection group were 67%, 42%, and 10%, respectively. The 5-year survival
      rate in the simultaneous resection group was 23%; overall survival differed
      significantly between the two groups (P=0.037). Median disease-free survival
      (DFS) times were 19.1 months in the simultaneous resection group and 8.8 months
      in the delayed resection group. DFS differed significantly between the two
      groups. CONCLUSIONS: Simultaneous colorectal and hepatic resection is safe and
      exhibits advantages in the long-time survival of patients.

PMID- 27877013
TI  - The association of TNF-308 (G/A) gene polymorphisms and hepatocellular carcinoma
      risk: a meta-analysis.
AB  - OBJECTIVE: Many studies have examined the association between the TNF-308 G/A
      polymorphism gene polymorphisms and hepatocellular carcinoma risk in various
      populations, but their results have been inconsistent. To assess this
      relationship more precisely, a meta-analysis was performed. METHODS: The PubMed
      and CNKI (China National Knowledge Infrastructure) database was searched for case
      control studies. Odds ratios (OR) with 95% CIs were used to determine the
      strength of association between the TNF-308 G/A polymorphisms and HCC risk. The
      pooled ORs for the risk associated with the TNF-308 G/A genotype, the A carriers
      (A/G + A/A) vs. the wild-type homozygotes (G/G), A/A vs. G/G were calculated,
      respectively. Subgroup analyses were done by ethnicity and smoking status.
      Heterogeneity assumptions were assessed by chi-square-based Q-test. RESULTS:
      Ultimately, 21 studies, comprising 2,923 hepatocellular carcinoma cases and 4,323
      controls were included. Overall, the A carriers (G/A + A/A) vs. the wild-type
      homozygotes (G/G), the pooled OR was 1.05 (95% CI, 0.93-1.19; P=0.000 for
      heterogeneity), for A/A vs. G/G the pooled OR was 1.07 (95% CI, 0.95-1.21;
      P=0.007 for heterogeneity). In the stratified analysis by ethnicity, the
      significantly risks were found among non-Asians. However, for Asians,
      significantly risks were not found. CONCLUSIONS: The TNF-308 G/A polymorphisms
      are not associated with hepatocellular carcinoma risk among Asians, but for non
      Asians.

PMID- 27877014
TI  - Prognostic potential of an immune score based on the density of CD8+ T cells,
      CD20+ B cells, and CD33+/p-STAT1+ double-positive cells and HMGB1 expression
      within cancer nests in stage IIIA gastric cancer patients.
AB  - OBJECTIVE: There is heterogeneity in the prognosis of gastric cancers staged
      according to the tumornodes- metastasis (TNM) system. This study evaluated the
      prognostic potential of an immune score system to supplement the TNM staging
      system. METHODS: An immunohistochemical analysis was conducted to assess the
      density of T cells, B cells, and myeloid-derived suppressor cells (MDSCs) in
      cancer tissues from 100 stage IIIA gastric cancer patients; the expression of the
      high-mobility group protein B1 (HMGB1) was also evaluated in cancer cells. The
      relationship between the overall survival (OS), disease-free survival (DFS), and
      immunological parameters was analyzed. RESULTS: An immune score system was
      compiled based on the prognostic role of the density of T cells, B cells, MDSCs,
      and the expression of HMGB1 in cancer tissues. The median 5-year survival of this
      group of patient was 32%. However, the 5-year survival rates of 80.0%, 51.7%, 0%,
      5.8%, and 0% varied among the patients with an immune score of 4 to those with an
      immune score of 0 based on the immune score system, respectively. Similarly,
      differences in DFS rates were observed among the immune score subgroups.
      CONCLUSIONS: An immune score system could effectively identify the prognostic
      heterogeneity within stage IIIA gastric cancer patients, implying that this
      immune score system may potentially supplement the TNM staging system, and help
      in identifying a more homogeneous group of patients who on the basis of prognosis
      can undergo adjuvant therapy.

PMID- 27877015
TI  - Rainbow glare after laser-assisted in situ keratomileusis: a review of
      literature.
AB  - This article reviews the current literature pertaining to rainbow glare (RG),
      including incidence rate, clinical presentation, etiology, prognosis, and
      management. RG is a rare optical complication of femtosecond laser-assisted in
      situ keratomileusis that results in patients seeing an array of spectral bands
      surrounding point sources of light under mesopic and scotopic conditions. The
      mechanism is thought to be a consequence of the formation of a transmissive
      diffraction grating on the posterior surface of the corneal flap created by the
      FS laser. RG has a good prognosis and is usually self-limiting. Persistent RG
      with concomitant residual refractive error may warrant lifting the flap and
      photoablating the posterior surface of the flap. Patients with persistent RG and
      no residual refractive error should be considered candidates for phototherapeutic
      keratectomy on the posterior flap surface.

PMID- 27877016
TI  - Clinical utility of antimicrobial susceptibility measurement plate covering
      formulated concentrations of various ophthalmic antimicrobial drugs.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical utility of SG17,
      an ophthalmic antimicrobial susceptibility measurement plate. DESIGN: This was a
      multicenter, retrospective, observational study. PATIENTS AND METHODS: Using
      clinical isolates from patients with ocular infections, drug susceptibility
      testing using the Clinical Laboratory and Standards Institute standards was
      routinely conducted at five facilities. The minimum inhibitory concentrations of
      the isolated strains were determined using SG17 at the Research Foundation for
      Microbial Diseases of Osaka University. The records of antimicrobial drugs used
      and the therapeutic course were evaluated for all cases. The susceptibility
      results from SG17 and routine methods used at each facility were compared.
      RESULTS: A total of 112 bacterial strains were isolated from 92 patients. Of
      these cases, keratitis was the most common (52.2%), followed by conjunctivitis
      (21.7%) and others (26.1%). Principal signs and symptoms resolved in all
      patients, indicating that therapeutic effects had been achieved. With SG17, drug
      susceptibility was determined in 98.9% of isolates compared with 30.4% of
      isolates determined using conventional methods. By adapting the Clinical
      Laboratory and Standards Institute standards to SG17 results, we found that 91.3%
      of patients were susceptible and 7.6% were resistant. In five patients, drugs
      with a resistant evaluation were initially administered with no effect, and the
      patients were then switched to drugs with a susceptible evaluation with final
      resolution, indicating agreement of clinical results with SG17. CONCLUSION: SG17
      can be used to determine drug susceptibility to antimicrobial agents currently
      used in ophthalmic practice. SG17 is useful for selecting antimicrobial drugs.

PMID- 27877017
TI  - Study of the antibacterial and antifungal activities of synthetic benzyl
      bromides, ketones, and corresponding chalcone derivatives.
AB  - Several applications of chalcones and their derivatives encouraged researchers to
      increase their synthesis as an alternative for the treatment of pathogenic
      bacterial and fungal infections. In the present study, chalcone derivatives were
      synthesized through cross aldol condensation reaction between 4-(N,N
      dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic
      ketones were synthesized through nucleophilic substitution reaction between 4
      hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic
      ketones, and corresponding chalcone derivatives were evaluated for their
      activities against eleven clinical pathogenic Gram-positive, Gram-negative
      bacteria, and three pathogenic fungi by the disk diffusion method. The minimum
      inhibitory concentration was determined by the microbroth dilution technique. The
      results of the present study demonstrated that benzyl bromide derivatives have
      strong antibacterial and antifungal properties as compared to synthetic chalcone
      derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity
      against Gram-positive bacteria and fungi but moderate activity against Gram
      negative bacteria. Therefore, these compounds may be considered as good
      antibacterial and antifungal drug discovery. However, substituted ketones (2a-b)
      as well as chalcone derivatives (3a-c) showed no activity against all the tested
      strains except for ketone (2c), which showed moderate activity against Candida
      albicans.

PMID- 27877018
TI  - More frequent IgD and reduced CD200 expression in Chinese patients younger than
      50 years old with multiple myeloma: a multicenter analysis.
AB  - We retrospectively analyzed the presenting features and survival of 194 newly
      diagnosed patients with multiple myeloma in the People's Republic of China.
      Compared with older patients, younger patients had a higher percentage of IgD
      isotype, lower percentage of International Staging System Stage 3 disease, higher
      albumin level, and lower frequency of high beta2-microglobulin and CD200
      expression. There was no difference in sex, Durie-Salmon stage, bone lesion
      degree, creatinine, lactate dehydrogenase, fluorescence in situ hybridization,
      and expression of other antigens. Among all 940 newly diagnosed patients with
      multiple myeloma, those younger than 50 years had better overall survival and
      progression-free survival than older patients. Of these patients, 457 were
      treated with a bortezomib-containing regimen, and 450 received conventional
      therapy. Younger patients treated with bortezomib had better overall survival and
      progression-free survival than older patients. However, younger patients treated
      with conventional therapy had the same survival as older patients.

PMID- 27877019
TI  - Comment on the case report "Possible association between acetazolamide
      administration during pregnancy and multiple congenital malformations".

PMID- 27877020
TI  - Improved oral bioavailability of 20(R)-25-methoxyl-dammarane-3beta, 12beta, 20
      triol using nanoemulsion based on phospholipid complex: design, characterization,
      and in vivo pharmacokinetics in rats.
AB  - The aim of the study was to improve the oral absorption of the compound 25-OCH3
      PPD with poor hydrophilicity and lipophilicity. 25-OCH3-PPD-phospholipid complex
      was prepared by solvent evaporation, then characterized by differential scanning
      calorimetry, scanning electron microscopy, and infrared absorption spectroscopy.
      The aqueous solubility and oil-water partition coefficient were compared with the
      free compound. A nanoemulsion loaded with 25-OCH3-PPD-phospholipid complex was
      developed by dissolving the complex in water in the presence of hydrophilic
      surfactant under sonication. After oral administration of the nanoemulsion and
      the suspension of 25-OCH3-PPD in rats, the concentrations of 25-OCH3-PPD in
      plasma were determined by high-performance liquid chromatography-tandem mass
      spectrometry method. The results showed that the solubility of the complex in
      water and n-octanol was enhanced. The oil-water partition coefficient improved
      1.7 times. Peak plasma concentration and area under the curve(0-24 h) of the
      nanoemulsion of 25-OCH3-PPD-phospholipid complex were higher than that of free
      compound by 3.9- and 3.5-folds.

PMID- 27877021
TI  - Medicine-related services in community pharmacy: public preferences for pharmacy
      attributes and promotional methods and comparison with pharmacists' perceptions.
AB  - BACKGROUND: Public awareness of pharmacy services designed to support the use of
      medicines is low, yet little is known about how the public view promotion of
      these services, or their preferences for the attributes of pharmacies from which
      they would like to receive them. OBJECTIVE: To compare the public's preferred
      attributes of pharmacies and methods for promoting medicine-related services with
      community pharmacists' perceptions of their customers' views. METHODS: Parallel
      surveys were conducted in South East England, using a street survey for the
      general public and a postal survey for community pharmacists. RESULTS: Response
      rates were as follows: public 47.2% (1,000/2,012) and pharmacists 40.8%
      (341/836). Pharmacists' perceptions of customer preferences for using the same
      pharmacy, independent ownership, and personal knowledge of the pharmacist were
      higher than actual public preferences. More pharmacists than public respondents
      also believed that approachability and previous good service would be important.
      The public's desires for long opening hours and for a pharmacy with a good
      relationship with their doctor's surgery were higher than pharmacists believed.
      The majority of the public prefer not to interrupt a pharmacist who is busy in
      the dispensary, which was not perceived by pharmacists as a factor. Pharmacists'
      perceptions aligned more with the preferences of regular medicine users and
      frequent pharmacy users. Both groups viewed direct recommendation as the most
      effective approach for promoting pharmacy services, particularly by doctors and
      pharmacy staff. Pharmacists' expectations of the effectiveness of posters and
      mass media methods were much higher than those of the public. CONCLUSION:
      Pharmacists and pharmacy owners must ensure good relationships with local medical
      practices to enable them to maximize opportunities for using the promotional
      methods judged most effective in encouraging the use of medicine-related
      services. Staff must be approachable and enable access to pharmacists, ensuring
      that perceptions of pharmacist busyness are not a deterrent.

PMID- 27877023
TI  - Impacts of fixed orthodontic appliance and clear-aligner on daily performance in
      adult patients with moderate need for treatment [Retraction].
AB  - [This retracts the article on p. 1639 in vol. 10, PMID: 27616881.].

PMID- 27877022
TI  - Development of internalized and personal stigma among patients with and without
      HIV infection and occupational stigma among health care providers in Southern
      China.
AB  - BACKGROUND: HIV/AIDS-related stigma is a major barrier of access to care for
      those infected with HIV. The aim of this study was to examine, validate, and
      adapt measuring scales of internalized, personal, and occupational stigma
      developed in Africa into a Chinese context. METHODS: A cross-sectional study was
      conducted from January to September 2015 in Kunming, People's Republic of China.
      Various scales were constructed on the basis of the previous studies with
      modifications by experts using exploratory and confirmatory factor analyses (EFA
      + CFA). Validation of the new scales was done using multiple linear regression
      models and hypothesis testing of the factorial structure invariance. RESULTS: The
      numbers of subjects recruited for the development/validation samples were 696/667
      HIV-positive patients, 699/667 non-HIV patients, and 157/155 health care
      providers. EFA revealed a two-factor solution for internalized and personal
      stigma scales (guilt/blaming and being refused/refusing service), which were
      confirmed by CFA with reliability coefficients (r) of 0.869 and 0.853,
      respectively. The occupational stigma scale was found to have a three-factor
      structure (blaming, professionalism, and egalitarianism) with a reliability
      coefficient (r) of 0.839. Higher correlations of factors in the HIV patients
      (r=0.537) and non-HIV patients (r=0.703) were observed in contrast to low-level
      correlations (r=0.231, 0.286, and 0.266) among factors from health care
      providers. CONCLUSION: The new stigma scales are valid and should be used to
      monitor HIV/AIDS stigma in different groups of Chinese people in health care
      settings.

PMID- 27877024
TI  - Understanding the physical, social, and emotional experiences of people with
      uncontrolled Type 2 diabetes: a qualitative study.
AB  - PURPOSE: The purpose of this study was to identify the perceptions, barriers, and
      facilitators of self-management of Type 2 diabetes mellitus (T2DM) to determine
      the factors to consider when developing and implementing a person-centered
      intervention in patients with poor glycemic control attending primary care.
      METHODS: This was a qualitative study conducted in 6 primary care health centers
      in Catalonia. Patients who had been diagnosed with T2DM and had glycated
      hemoglobin of 9% or more were included. The sampling method was opportunistic,
      accounting for gender, age, duration of diabetes, and type of treatment. Forty
      three semi-structured interviews were conducted. Thematic content analysis was
      performed. RESULTS: The patients perceived the diagnosis of T2DM as a threat to
      their health, and the diagnosis generated cognitive and emotional representations
      of T2DM. The emotions associated with the diagnosis included fear of the future,
      worry, denial, sadness, and dejection. The patients also wondered if there could
      have been an error in their test results because they did not present any
      symptoms. These representations, both cognitive and emotional, can produce
      specific effects in adaptation processes and require different approach
      strategies, specifically regarding diet, physical activity, and pharmacological
      treatment. Finally, specific aspects regarding the acceptability and adaptability
      of the implementation of a new intervention were expressed. CONCLUSION: Patients
      with T2DM and very poor glycemic control expressed difficulty achieving a balance
      between the needs and demands of managing and controlling T2DM because they felt
      it strongly interfered in their daily lives.

PMID- 27877026
TI  - Pharmaceutical interventions by collaboration between staff pharmacists and
      clinical pharmacists and implementation of Joint Commission International
      Accreditation Standards on medication use may optimize pharmacotherapy in
      geriatric patients.

PMID- 27877025
TI  - Medication knowledge of patients hospitalized for heart failure at admission and
      after discharge.
AB  - BACKGROUND: A substantial aspect of health literacy is the knowledge of
      prescribed medication. In chronic heart failure, incomplete intake of prescribed
      drugs (medication non-adherence) is inversely associated with clinical prognosis.
      Therefore, we assessed medication knowledge in a cohort of patients with
      decompensated heart failure at hospital admission and after discharge in a
      prospective, cross-sectional study. METHODS: One hundred and eleven patients
      presenting at the emergency department with acute decompensated heart failure
      were included (mean age 78.4+/-9.2, 59% men) in the study. Patients' medication
      knowledge was assessed during individual interviews at baseline, course of
      hospitalization, and 3 months after discharge. Individual responses were compared
      with the medical records of the referring general practitioner. RESULTS: Median N
      terminal prohormone of brain natriuretic peptide plasma concentration in the
      overall population at baseline was 4,208 pg/mL (2,023-7,101 pg/mL [interquartile
      range]), 20 patients died between the second and third interview. The number of
      prescribed drugs increased from 8+/-3 at baseline to 9+/-3 after 3 months. The
      majority of patients did not know the correct number of their drugs. Medication
      knowledge decreased continuously from baseline to the third interview. At
      baseline, 37% (n=41) of patients stated the correct number of drugs to be taken,
      whereas only 18% (n=16) knew the correct number 3 months after discharge
      (P=0.008). Knowledge was inversely related to N-terminal prohormone of brain
      natriuretic peptide levels. CONCLUSION: Medication knowledge of patients with
      acute decompensated heart failure is poor. Despite care in a university hospital,
      patients' individual medication knowledge decreased after discharge. The study
      reveals an urgent need for better strategies to improve and promote the knowledge
      of prescribed medication in these very high-risk patients.

PMID- 27877027
TI  - Fatigue as a long-term risk factor for limitations in instrumental activities of
      daily living and/or mobility performance in older adults after 10 years.
AB  - OBJECTIVES: Decline in the performance of instrumental activities of daily living
      (IADL) and mobility may be preceded by symptoms the patient experiences, such as
      fatigue. The aim of this study is to investigate whether self-reported non-task
      specific fatigue is a long-term risk factor for IADL-limitations and/or mobility
      performance in older adults after 10 years. METHODS: A prospective study from two
      previously conducted cross-sectional studies with 10-year follow-up was conducted
      among 285 males and 249 females aged 40-79 years at baseline. Fatigue was
      measured by asking "Did you feel tired within the past 4 weeks?" (males) and "Do
      you feel tired?" (females). Self-reported IADLs were assessed at baseline and
      follow-up. Mobility was assessed by the 6-minute walk test. Gender-specific
      associations between fatigue and IADL-limitations and mobility were estimated by
      multivariable logistic and linear regression models. RESULTS: A total of 18.6% of
      males and 28.1% of females were fatigued. After adjustment, the odds ratio for
      fatigued versus non-fatigued males affected by IADL-limitations was 3.3
      (P=0.023). In females, the association was weaker and not statistically
      significant, with odds ratio being 1.7 (P=0.154). Fatigued males walked 39.1 m
      shorter distance than those non-fatigued (P=0.048). For fatigued females, the
      distance was 17.5 m shorter compared to those non-fatigued (P=0.479). CONCLUSION:
      Our data suggest that self-reported fatigue may be a long-term risk factor for
      IADL-limitations and mobility performance in middle-aged and elderly males but
      possibly not in females.

PMID- 27877028
TI  - Efficacy of a trunk orthosis with joints providing resistive force on low back
      load during level walking in elderly persons.
AB  - PURPOSE: The effects of lumbosacral and spinal orthoses on low back pain and gait
      are not exactly clear. We previously developed a trunk orthosis with joints
      providing resistive force on low back load to decrease such load, and confirmed
      its positive effects during level walking in healthy young adults. Therefore, we
      aimed to determine the efficacy of this trunk orthosis during level walking in
      healthy elderly subjects. METHODS: Fifteen community-dwelling elderly subjects
      performed level walking at a self-selected speed without an orthosis, with our
      orthosis, and with a lumbosacral orthosis. Kinematic and kinetic data were
      recorded using a three-dimensional motion analysis system, and erector spinae
      activity was recorded by electromyography. RESULTS: When comparing the three
      conditions, our orthosis showed the following effects: it decreased the peak
      extension moment, increased the peak flexion moment, decreased the lateral
      bending angle, increased the peak thoracic extension angle, and had significantly
      lower erector spinae activity and significantly larger peak pelvic forward tilt
      angles. CONCLUSION: Our orthosis with joints providing resistive force decreased
      low back load and modified trunk and pelvis alignments during level walking in
      healthy elderly people.

PMID- 27877029
TI  - Comments on the paper "Efficacies of globus pallidus stimulation and subthalamic
      nucleus stimulation for advanced Parkinson's disease: a meta-analysis of
      randomized controlled trials".

PMID- 27877030
TI  - Application of a diagnostic algorithm for the rare deficient variant Mmalton of
      alpha-1-antitrypsin deficiency: a new approach.
AB  - BACKGROUND AND OBJECTIVES: Alpha-1-antitrypsin deficiency (AATD) is associated
      with a high risk for the development of early-onset emphysema and liver disease.
      A large majority of subjects with severe AATD carry the ZZ genotype, which can be
      easily detected. Another rare pathologic variant, the Mmalton allele, causes a
      deficiency similar to that of the Z variant, but it is not easily recognizable
      and its detection seems to be underestimated. Therefore, we have included a rapid
      allele-specific genotyping assay for the detection of the Mmalton variant in the
      diagnostic algorithm of AATD used in our laboratory. The objective of this study
      was to test the usefulness of this new algorithm for Mmalton detection. MATERIALS
      AND METHODS: We performed a retrospective revision of all AATD determinations
      carried out in our laboratory over 2 years using the new diagnostic algorithm.
      Samples with a phenotype showing one or two M alleles and AAT levels discordant
      with that phenotype were analyzed using the Mmalton allele-specific genotyping
      assay. RESULTS: We detected 49 samples with discordant AAT levels; 44 had the MM
      and five the MS phenotype. In nine of these samples, a single rare Mmalton
      variant was detected. During the study period, two family screenings were
      performed and four additional Mmalton variants were identified. CONCLUSION: The
      incorporation of the Mmalton allele-specific genotyping assay in the diagnostic
      algorithm of AATD resulted in a faster and cheaper method to detect this allele
      and avoided a significant delay in diagnosis when a sequencing assay was
      required. This methodology can be adapted to other rare variants. Standardized
      algorithms are required to obtain conclusive data of the real incidence of rare
      AAT alleles in each region.

PMID- 27877031
TI  - The association between inhaled corticosteroid and pneumonia in COPD patients:
      the improvement of patients' life quality with COPD in Taiwan (IMPACT) study.
AB  - To investigate the association between inhaled corticosteroid (ICS) exposure
      patterns and the risk of pneumonia in chronic obstructive pulmonary disease
      (COPD) patients, we performed a nested case-control study. Between 1998 and 2010,
      51,739 patients, including 19,838 cases of pneumonia, were matched to 74,849
      control subjects selected from a cohort of COPD patients using ICSs via risk-set
      sampling of the database constructed by the National Health Research Institutes
      of Taiwan. After adjusting for covariates, the current use of ICSs was associated
      with a 25% increase in the risk of pneumonia (odds ratio [OR] =1.25, 95%
      confidence interval [CI] =1.20-1.30), and there was an increase in the OR with
      increase in the average daily dosage. Additionally, users of
      fluticasone/salmeterol, fluticasone, and either fluticasone/salmeterol or
      fluticasone were more likely to be at a higher risk of pneumonia (OR =1.35, 95%
      CI =1.28-1.41; OR =1.22, 95% CI =1.10-1.35; and OR =1.33, 95% CI =1.27-1.39,
      respectively). In contrast, there were no statistically significant associations
      between the risk of pneumonia and the use of budesonide/formoterol, budesonide,
      or either budesonide/formoterol or budesonide. In conclusion, ICSs are
      significantly associated with an increased risk of pneumonia in COPD patients.
      The effect is prominent for fluticasone-containing ICSs but not for budesonide
      containing ICSs.

PMID- 27877033
TI  - Combination therapy of inhaled steroids and long-acting beta2-agonists in asthma
      COPD overlap syndrome.
AB  - BACKGROUND: The efficacy of inhaled corticosteroids (ICSs)/long-acting beta2
      agonist (LABA) treatment in patients with asthma-chronic obstructive pulmonary
      disease (COPD) overlap syndrome (ACOS) compared to patients with COPD alone has
      rarely been examined. This study aimed to evaluate the clinical efficacy for the
      improvement of lung function after ICS/LABA treatment in patients with ACOS
      compared to COPD alone patients. METHODS: Patients with stable COPD were selected
      from the Korean Obstructive Lung Disease (KOLD) cohort. Subjects began a 3-month
      ICS/LABA treatment after a washout period. ACOS was defined when the patients had
      1) a personal history of asthma, irrespective of age, and wheezing in the last 12
      months in a self-reported survey and 2) a positive bronchodilator response.
      RESULTS: Among 152 eligible COPD patients, 45 (29.6%) fulfilled the criteria for
      ACOS. After a 3-month treatment with ICS/LABA, the increase in forced expiratory
      volume in 1 second (FEV1) was significantly greater in ACOS patients than in
      those with COPD alone (240.2+/-33.5 vs 124.6+/-19.8 mL, P=0.002). This increase
      in FEV1 persisted even after adjustment for confounding factors (adjusted
      P=0.002). According to severity of baseline FEV1, the ACOS group showed a
      significantly greater increase in FEV1 than the COPD-alone group in patients with
      mild-to-moderate airflow limitation (223.2+/-42.9 vs 84.6+/-25.3 mL, P=0.005),
      whereas there was no statistically significant difference in patients with severe
      to very severe airflow limitation. CONCLUSION: This study provides clinical
      evidence that ACOS patients with mild-to-moderate airflow limitation showed a
      greater response in lung function after 3 months of ICS/LABA combination
      treatment.

PMID- 27877032
TI  - Pulmonary complications after abdominal surgery in patients with mild-to-moderate
      chronic obstructive pulmonary disease.
AB  - Postoperative pulmonary complications (PPCs) are one of the most important causes
      of postoperative morbidity and mortality after abdominal surgery. Although
      chronic obstructive pulmonary disease (COPD) has been considered a risk factor
      for PPCs, it remains unclear whether mild-to-moderate COPD is a risk factor. This
      retrospective cohort study included 387 subjects who underwent abdominal surgery
      with general anesthesia in a tertiary referral hospital. PPCs included pneumonia,
      pulmonary edema, pulmonary thromboembolism, atelectasis, and acute exacerbation
      of COPD. Among the 387 subjects, PPCs developed in 14 (12.0%) of 117 patients
      with mild-to-moderate COPD and in 13 (15.1%) of 86 control patients. Multiple
      logistic regression analysis revealed that mild-to-moderate COPD was not a
      significant risk factor for PPCs (odds ratio [OR] =0.79; 95% confidence interval
      [CI] =0.31-2.03; P=0.628). However, previous hospitalization for respiratory
      problems (OR =4.20; 95% CI =1.52-11.59), emergency surgery (OR =3.93; 95% CI
      =1.75-8.82), increased amount of red blood cell (RBC) transfusion (OR =1.09; 95%
      CI =1.05-1.14 for one pack increase of RBC transfusion), and laparoscopic surgery
      (OR =0.41; 95% CI =0.18-0.93) were independent predictors of PPCs. These findings
      suggested that mild-to-moderate COPD may not be a significant risk factor for
      PPCs after abdominal surgery.

PMID- 27877034
TI  - Persistent disabling breathlessness in chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the prevalence, change in breathlessness status over
      time, and risk factors for disabling and persistent disabling breathlessness in
      relation to treatments in chronic obstructive pulmonary disease (COPD). MATERIALS
      AND METHODS: Longitudinal analysis of data from the Swedish National Register of
      COPD with breathlessness measured using modified Medical Research Council (mMRC)
      scores at two subsequent visits. Prevalence of disabling breathlessness (mMRC >=2
      at baseline) and persistent disabling breathlessness (disabling breathlessness at
      baseline and follow-up) was investigated in relation to COPD treatment. Risk
      factors for disabling breathlessness, change from non-disabling to disabling
      breathlessness, and persistent disabling breathlessness were analyzed using
      multiple logistic regression. RESULTS: A total of 1,689 patients were included in
      the study with a median follow-up of 12 months (interquartile range: 4 months).
      Prevalence of disabling breathlessness was 54% at baseline. Persistent disabling
      breathlessness was present in 43% of patients despite treatment and in 74% of
      patients despite combined inhaled triple therapy and physiotherapy. Risk factors
      for disabling breathlessness or change to disabling breathlessness were higher
      age, lower lung function, frequent exacerbations, obesity, heart failure,
      depression, and hypoxic respiratory failure (all P<0.05). Persistent disabling
      breathlessness was associated with lower lung function and ischemic heart disease
      (all P<0.05). CONCLUSION: Disabling breathlessness is common in COPD despite
      treatment, which calls for improved symptomatic treatments and consideration of
      factors influencing disabling breathlessness. Factors influencing disabling
      breathlessness should be considered for COPD management.

PMID- 27877035
TI  - Association between hemoglobin and prognosis in patients admitted to hospital for
      COPD.
AB  - Low concentrations of hemoglobin have previously been demonstrated in many
      patients with COPD. There is evidence of anemia as a prognostic factor in acute
      exacerbations, but the detailed relationship between concentrations of hemoglobin
      and mortality is not known. A register-based cohort of patients admitted for the
      first time to Danish hospitals for acute exacerbations of COPD from 2007 through
      2012 was established. Age, sex, comorbidities, medication, renal function, and
      concentrations of hemoglobin were retrieved. Sex-specific survival analyses were
      fitted for different rounded concentrations of hemoglobin. The cohort encompassed
      6,969 patients. Hemoglobin below 130 g/L was present in 39% of males and below
      120 g/L in 24% of females. The in-hospital mortality rates for patients with
      hemoglobin below or above these limits were 11.6% and 5.4%, respectively. After
      discharge, compared to hemoglobin 130 g/L, the hazard ratio (HR) for males with
      hemoglobin 120 g/L was 1.45 (95% confidence interval [CI] 1.22-1.73), adjusted HR
      1.37 (95% CI 1.15-1.64). Compared to hemoglobin 120 g/L, the HR for females with
      hemoglobin 110 g/L was 1.4 (95% CI 1.17-1.68), adjusted HR 1.28 (95% CI 1.06
      1.53). In conclusion, low concentrations of hemoglobin are frequent in COPD
      patients with acute exacerbations, and predict long-term mortality.

PMID- 27877036
TI  - Modification of the surface of superparamagnetic iron oxide nanoparticles to
      enable their safe application in humans.
AB  - Combined individually tailored methods for diagnosis and therapy (theragnostics)
      could be beneficial in destructive diseases, such as rheumatoid arthritis.
      Nanoparticles are promising candidates for theragnostics due to their excellent
      biocompatibility. Nanoparticle modifications, such as improved surface coating,
      are in development to meet various requirements, although safety concerns mean
      that modified nanoparticles require further review before their use in medical
      applications is permitted. We have previously demonstrated that iron oxide
      nanoparticles with amino-polyvinyl alcohol (a-PVA) adsorbed on their surfaces
      have the unwanted effect of increasing human immune cell cytokine secretion. We
      hypothesized that this immune response was caused by free-floating PVA. The aim
      of the present study was to prevent unwanted immune reactions by further surface
      modification of the a-PVA nanoparticles. After cross-linking of PVA to
      nanoparticles to produce PVA-grafted nanoparticles, and reduction of their zeta
      potential, the effects on cell viability and cytokine secretion were analyzed.
      PVA-grafted nanoparticles still stimulated elevated cytokine secretion from human
      immune cells; however, this was inhibited after reduction of the zeta potential.
      In conclusion, covalent cross-linking of PVA to nanoparticles and adjustment of
      the surface charge rendered them nontoxic to immune cells, nonimmunogenic, and
      potentially suitable for use as theragnostic agents.

PMID- 27877037
TI  - Acute and subacute toxicity profiles of thymoquinone-loaded nanostructured lipid
      carrier in BALB/c mice.
AB  - BACKGROUND: Thymoquinone (TQ), the predominant active lipophilic component in
      Nigella sativa seed oil, has a variety of pharmacological properties such as
      anticancer activities. However, translation of TQ to clinical phase is still not
      possible due to its hydrophobic properties. This problem can be solved by
      encapsulating it in nanoformulations to enhance its pharmacological properties.
      In our previous study, TQ has been successfully encapsulated in a nanostructured
      lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical
      properties such as high encapsulation efficiency, high drug-loading capacity,
      particle diameter less than 100 nm, and stability up to 2 years. In vitro studies
      also proved that TQNLC exhibited antiproliferative activity toward breast and
      cervical cancer cell lines. However, no toxicity profile related to this
      formulation has been reported. In this study, we determine and compare the in
      vivo toxicity of both TQNLC and TQ. MATERIALS AND METHODS: The in vivo toxicity
      (acute and subacute toxicity) study was carried out by oral administration of
      TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body
      weight ratio, hematological profile, biochemistry profile, and histopathological
      changes were analyzed. RESULTS: In acute toxicity, TQ that is loaded in
      nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It
      can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity
      of the compound. In the subacute toxicity study, oral administration of 100 mg/kg
      of TQNLC and TQ did not cause mortality to either male or female but resulted in
      toxicity to the liver. It is postulated that long-term consumption of TQNLC and
      TQ may cause toxicity to the liver but not to the extent of altering the
      functions of the organ. For both treatments, the no observed adverse effect level
      (NOAEL) was found to be 10 mg/kg/d for mice in both sexes. CONCLUSION: For long
      term oral consumption, TQ and TQNLC at a dose of 10 mg/kg is safe in mice and
      does not exert any toxic effect. The results provide safety information of TQNLC,
      which would further help researchers in clinical use.

PMID- 27877038
TI  - Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive
      drug delivery system for vaginal administration of protein therapeutics: improved
      stability, mucin-dependent release and effective intravaginal placement.
AB  - Effective interaction between mucoadhesive drug delivery systems and mucin is the
      basis of effective local placement of drugs to play its therapeutic role after
      mucosal administration including vaginal use, which especially requires prolonged
      drug presence for the treatment of gynecological infectious diseases. Our
      previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated
      their strong interaction with mucin and mucin-sensitive release profiles of the
      model protein therapeutics interferon (IFN) in vitro, but their poor stability
      and obvious tendency to aggregate over time severely limited future application.
      In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable
      mucoadhesive drug delivery system where the negative charges conferred by
      sulfonate groups prevented aggregation of nanoparticles and the phenylboronic
      acid groups ensured effective interaction with mucin over a wide pH range.
      Results suggested that PBNP-S were of spherical morphology with narrow size
      distribution (123.5 nm, polydispersity index 0.050), good stability over a wide
      pH range and 3-month storage and considerable in vitro mucoadhesion capability at
      vaginal pH as shown by mucin adsorption determination. IFN could be loaded to
      PBNP-S by physical adsorption with high encapsulation efficiency and released in
      a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal
      imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent
      assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and
      maintain intravaginal IFN level for much longer time than IFN solution (24 hours
      vs several hours) without obvious histological irritation to vaginal mucosa after
      vaginal administration to mice. In summary, good stability, easy loading and
      controllable release of protein therapeutics, in vitro and in vivo mucoadhesive
      properties and local safety of PBNP-S suggested it as a promising nanoscale
      mucoadhesive drug delivery system for vaginal administration of protein
      therapeutics.

PMID- 27877040
TI  - Intestinal anti-inflammatory effects of RGD-functionalized silk fibroin
      nanoparticles in trinitrobenzenesulfonic acid-induced experimental colitis in
      rats.
AB  - BACKGROUND: Current treatment of inflammatory bowel disease is based on the use
      of immunosuppressants or anti-inflammatory drugs, which are characterized by
      important side effects that can limit their use. Previous research has been
      performed by administering these drugs as nanoparticles that target the ulcerated
      intestinal regions and increase their bioavailability. It has been reported that
      silk fibroin can act as a drug carrier and shows anti-inflammatory properties.
      PURPOSE: This study was designed to enhance the interaction of the silk fibroin
      nanoparticles (SFNs) with the injured intestinal tissue by functionalizing them
      with the peptide motif RGD (arginine-glycine-aspartic acid) and to evaluate the
      intestinal anti-inflammatory properties of these RGD-functionalized silk fibroin
      nanoparticles (RGD-SFNs) in the trinitrobenzenesulfonic acid (TNBS) model of rat
      colitis. MATERIALS AND METHODS: SFNs were prepared by nanoprecipitation in
      methanol, and the linear RGD peptide was linked to SFNs using glutaraldehyde as
      the crosslinker. The SFNs (1 mg/rat) and RGD-SFNs (1 mg/rat) were administered
      intrarectally to TNBS-induced colitic rats for 7 days. RESULTS: The SFN
      treatments ameliorated the colonic damage, reduced neutrophil infiltration, and
      improved the compromised oxidative status of the colon. However, only the rats
      treated with RGD-SFNs showed a significant reduction in the expression of
      different pro-inflammatory cytokines (interleukin [IL]-1beta, IL-6, and IL-12)
      and inducible nitric oxide synthase in comparison with the TNBS control group.
      Moreover, the expression of both cytokine-induced neutrophil chemoattractant-1
      and monocyte chemotactic protein-1 was significantly diminished by the RGD-SFN
      treatment. However, both treatments improved the intestinal wall integrity by
      increasing the gene expression of some of its markers (trefoil factor-3 and
      mucins). CONCLUSION: SFNs displayed intestinal anti-inflammatory properties in
      the TNBS model of colitis in rats, which were improved by functionalization with
      the RGD peptide.

PMID- 27877039
TI  - Biosynthesis of gold nanoparticles by the extreme bacterium Deinococcus
      radiodurans and an evaluation of their antibacterial properties.
AB  - Deinococcus radiodurans is an extreme bacterium known for its high resistance to
      stresses including radiation and oxidants. The ability of D. radiodurans to
      reduce Au(III) and biosynthesize gold nanoparticles (AuNPs) was investigated in
      aqueous solution by ultraviolet and visible (UV/Vis) absorption spectroscopy,
      electron microscopy, X-ray diffraction (XRD), dynamic light scattering (DLS),
      Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron
      spectroscopy (XPS). D. radiodurans efficiently synthesized AuNPs from 1 mM
      Au(III) solution in 8 h. The AuNPs were of spherical, triangular and irregular
      shapes with an average size of 43.75 nm and a polydispersity index of 0.23 as
      measured by DLS. AuNPs were distributed in the cell envelope, across the cytosol
      and in the extracellular space. XRD analysis confirmed the crystallite nature of
      the AuNPs from the cell supernatant. Data from the FTIR and XPS showed that upon
      binding to proteins or compounds through interactions with carboxyl, amine,
      phospho and hydroxyl groups, Au(III) may be reduced to Au(I), and further reduced
      to Au(0) with the capping groups to stabilize the AuNPs. Biosynthesis of AuNPs
      was optimized with respect to the initial concentration of gold salt, bacterial
      growth period, solution pH and temperature. The purified AuNPs exhibited
      significant antibacterial activity against both Gram-negative (Escherichia coli)
      and Gram-positive (Staphylococcus aureus) bacteria by damaging their cytoplasmic
      membrane. Therefore, the extreme bacterium D. radiodurans can be used as a novel
      bacterial candidate for efficient biosynthesis of AuNPs, which exhibited
      potential in biomedical application as an antibacterial agent.

PMID- 27877041
TI  - Nanomedicine strategy for optimizing delivery to outer hair cells by surface
      modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules.
AB  - Targeted drug delivery to outer hair cells (OHCs) in the cochlea by nanomedicine
      strategies forms an effective therapeutic approach for treating hearing loss.
      Surface chemistry plays a deciding role in nanoparticle (NP) biodistribution, but
      its influence on such distribution in the cochlea remains largely unknown.
      Herein, we report the first systematic comparison of poly(lactic/glycolic acid)
      nanoparticles (PLGA NPs) with or without surface modification of hydrophilic
      molecules for optimizing the delivery to OHCs both in vitro and in vivo. NPs that
      were surface modified with poloxamer 407 (P407), chitosan, or methoxy
      poly(ethylene glycol) and the unmodified NPs were highly biocompatible with L929
      and House Ear Institute-organ of Corti 1 cells as well as cochlear tissues.
      Interestingly, among all the examined NPs, P407-PLGA NPs showed the greatest
      cellular uptake and prominent fluorescence in cochlear imaging. More importantly,
      we provide novel evidence that the surface-modified NPs reached the organ of
      Corti and were transported into the OHCs at a higher level. Together, these
      observations suggest that surface modification with hydrophilic molecules will
      allow future clinical applications of PLGA NPs, especially P407-PLGA NPs, in
      efficient hearing loss therapy.

PMID- 27877042
TI  - Effects of Carbopol(r) 934 proportion on nanoemulsion gel for topical and
      transdermal drug delivery: a skin permeation study.
AB  - Nanoemulsions (NEs) are used as transdermal drug delivery systems for systematic
      therapeutic purposes. We hypothesized that the skin permeation profile of an NE
      could be modulated by incorporating it into a hydrogel containing differing
      proportions of thickening agent. The objectives of this study were as follows: 1)
      to determine the stability and skin irritability of NE gels (NGs) containing 1%,
      2%, and 3% (w/w) Carbopol(r) 934 (CP934) (termed NG1, NG2, and NG3,
      respectively); 2) to compare the skin permeation profiles and drug deposition
      patterns of the NGs; and 3) to visualize the drug delivery routes of the NGs.
      Terbinafine and citral were incorporated into the NGs as model drugs. Ex vivo
      skin permeation tests indicated that the percutaneous flux rates of terbinafine
      decreased in the order NE (215 MUg/cm2) > NG1 (213 MUg/cm2) > NG2 (123 MUg/cm2) >
      NG3 (74.3 MUg/cm2). The flux rates of citral decreased in the order NE (1,026
      MUg/cm2) > NG1 (1,021 MUg/cm2) > NG2 (541 MUg/cm2) > NG3 (353 MUg/cm2). The NGs
      accumulated greater amounts of the drugs in the stratum corneum and less in the
      epidermis/dermis than did the NE (P<0.05) over a period of 12 h. Laser scanning
      confocal microscopy indicated that the NGs altered the main drug delivery routes
      from skin appendages to intercellular paths. Histological images suggested that
      perturbations to the skin structure, specifically the size of the epidermal
      intercellular spaces and the separation distance of dermal collagen bundles,
      could be significantly minimized by increasing the proportion of CP934. These
      results suggest that adjustments of the CP934 proportions can be used to modulate
      the skin permeation profiles of NGs for specific therapeutic purposes.

PMID- 27877043
TI  - Polycystic ovary syndrome and mental disorders: a systematic review and
      exploratory meta-analysis.
AB  - BACKGROUND: The association between depression, anxiety, and polycystic ovary
      syndrome (PCOS) is still unclear. Therefore, a systematic review and meta
      analysis was conducted to assess the rates of comorbid psychiatric disorders
      among women with PCOS compared to women without it. METHODS: PubMed/MEDLINE,
      Embase, PsycINFO, and Web of Science databases were searched from inception to
      November 27, 2015. Studies were eligible for inclusion if they were original
      reports in which the rates of mood (bipolar disorder, dysthymia, or major
      depressive disorder), obsessive-compulsive spectrum disorders, trauma- and
      stressor-related disorders, anxiety disorders or psychotic disorders, somatic
      symptom and related disorders, or eating disorders had been investigated among
      women with an established diagnosis of PCOS and compared with women without PCOS.
      Psychiatric diagnosis should have been established by means of a structured
      diagnostic interview or through a validated screening tool. Data were extracted
      and pooled using random effects models. RESULTS: Six studies were included in the
      meta-analysis; of these, five reported the rates of anxiety and six provided data
      on the rates of depression. The rate of subjects with anxiety symptoms was higher
      in patients with PCOS compared to women without PCOS (odds ratio (OR) =2.76; 95%
      confidence interval (CI) 1.26 to 6.02; Log OR =1.013; P=0.011). The rate of
      subjects with depressive symptoms was higher in patients with PCOS compared to
      women without PCOS (OR =3.51; 95% CI 1.97 to 6.24; Log OR =1.255; P<0.001).
      CONCLUSION: Anxiety and depression symptoms are more prevalent in patients with
      PCOS.

PMID- 27877044
TI  - Increased miR-132 level is associated with visual memory dysfunction in patients
      with depression.
AB  - BACKGROUND: Impaired visual memory seems to be a core feature of depression,
      while increased microRNA-132 (miR-132) levels have been widely reported in
      depression patients. The authors aimed to explore the relationship between miR
      132 changes and visual memory deficits in unmedicated patients with major
      depressive disorder (MDD). PATIENTS AND METHODS: A total of 62 medication-free
      MDD patients and 73 matched healthy controls (HCs) were tested for miR-132
      expression level in peripheral blood using quantitative real-time polymerase
      chain reaction. We used a computerized neurocognitive task from the Cambridge
      Neuropsychological Test Automated Battery (CANTAB) - pattern recognition memory
      (PRM) task - as a measurement of visual memory. The relationship between visual
      memory, miR-132 expression level, and clinical symptoms was explored in patients
      with MDD. RESULTS: Upregulated miR-132 expression levels were seen in MDD
      patients but not in HCs. Two-sample t-tests showed that MDD patients had
      decreased visual memory, mainly memory delayed compared to that of HCs.
      Correlation analyses revealed that in MDD patients, increased miR-132 expression
      levels were significantly correlated with visual memory as measured by the
      CANTABPRM. Hamilton Rating Scale for Anxiety scores were negatively correlated
      with PRM - number correct (immediate) and PRM - percent correct (immediate).
      LIMITATIONS: The main limitations were missing data and lack of follow-up
      studies. CONCLUSION: Our study suggests that increased miR-132 expression levels
      were associated with visual memory deficits, which may underlie the
      pathophysiology of MDD. In individuals with depression, immediate visual memory
      defects were positively correlated with anxiety symptoms.

PMID- 27877045
TI  - Serum low-density lipoprotein levels, statin use, and cognition in patients with
      coronary artery disease.
AB  - AIM: Statins have been associated with decreased cognition due to the effects of
      low concentrations of low-density lipoprotein (LDL) on brain function. This has
      remained controversial and is particularly relevant to patients with coronary
      artery disease (CAD), who have an increased risk of cognitive decline and are
      frequently prescribed statins. This study hypothesized that low concentration of
      LDL is associated with poor cognition in CAD patients using statins. It also
      explored the association between high-dose versus low-dose statins on cognition
      in this population. PATIENTS AND METHODS: Baseline cross-sectional data from a
      longitudinal study of 120 statin-using CAD patients were examined (mean statin
      duration 25+/-43 months). The main outcomes were measures of global cognition and
      cognitive domains, with poor cognition defined as cognitive performance <=1
      standard deviation below the population age and education adjusted means. A
      battery of cognitive tests was used to assess verbal memory, executive function,
      speed of processing, visuospatial memory, and global cognition. Adjusting for
      age, sex, education, and other covariates, multivariable logistic regression
      analyses assessed associations between low LDL levels (<1.5 mmol/L), statin use,
      and poor cognition. RESULTS: LDL levels were not associated with global cognition
      or individual cognitive domains. High-dose statin use was associated with higher
      visuospatial memory (odds ratio, OR [95% confidence interval, CI] =0.12 [0.02
      0.66], P=0.01) and executive functioning (OR =0.25 [0.06-0.99], P=0.05). This
      effect was independent of covariates such as LDL levels. CONCLUSION: Low LDL
      levels do not appear to be associated with poor cognition in CAD patients using
      statins. Whether high-dose statin use may have positive effects on cognition in
      CAD patients could be investigated in future studies.

PMID- 27877046
TI  - Comparative effect and safety of verapamil in keloid and hypertrophic scar
      treatment: a meta-analysis.
AB  - BACKGROUND: Keloids and hypertrophic scars are the most common types of
      pathological scarring. Traditionally, keloids have been considered as a result of
      aberrant wound healing, involving excessive fibroblast participation that is
      characterized by hyalinized collagen bundles. However, the usefulness of this
      characterization has been questioned. In recent years, studies have reported the
      appropriate use of verapamil for keloids and hypertrophic scars. METHODS:
      Searches were conducted on the databases Medline, Embase, Cochrane, PubMed, and
      China National Knowledge Infrastructure from 2006 to July 2016. State12.0 was
      used for literature review, data extraction, and meta-analysis. Treatment groups
      were divided into verapamil and nonverapamil group. Nonverapamil group includes
      steroids and intense pulsed light (IPL) therapy. Total effective rates include
      cure rate and effective rate. Cure: skin lesions were completely flattened,
      became soft and symptoms disappeared. Efficacy: skin lesions subsided, patient
      significantly reduced symptoms. Inefficient definition of skin was progression
      free or became worse. Random-effects model was used for the meta-analysis.
      RESULTS: Six studies that included 331 patients with keloids and hypertrophic
      scars were analyzed. Analysis of the total effective rate of skin healing was
      performed. The total effective rates in the two groups were 54.07% (verapamil)
      and 53.18% (nonverapamil), respectively. The meta-analysis showed that there was
      no difference between the two groups. We also compared the adverse reactions
      between the verapamil treatment group and the steroids treatment group in two
      studies, and the result indicated that the verapamil group showed less adverse
      reactions. CONCLUSION: There were no differences between the application of
      verapamil and nonverapamil group in keloids and hypertrophic scars treatment.
      Verapamil could act as an effective alternative modality in the prevention and
      treatment of keloid and hypertrophic scars. A larger number of studies are
      required to confirm our conclusion.

PMID- 27877047
TI  - Antiallergic effect of the atomized extract of rhizome of Curcuma longa, flowers
      of Cordia lutea and leaves of Annona muricata.
AB  - INTRODUCTION: Allergies are a problem that greatly affects the population, and
      hence the use of antiallergic medications is fairly widespread. However, these
      drugs have many adverse effects. The use of medicinal plants could be an option,
      but they need to be evaluated. OBJECTIVE: This study was designed to evaluate the
      antiallergic effect of the atomized extract of rhizome of Curcuma longa, flowers
      of Cordia lutea, and leaves of Annona muricata. MATERIALS AND METHODS: Twenty
      four New Zealand white albino rabbits were randomized into 2 groups. Group A
      received the atomized extract diluted in physiological saline (APS) and group B
      received it diluted in Freund's adjuvant (FA). Then, the back of each rabbit was
      divided into 4 quadrants. The A-I quadrant received only physiological saline.
      The A-I quadrants of each rabbit conformed the PS group. The following 3
      quadrants received the APS in 10 MUg/mL, 100 MUg/mL, and 1,000 MUg/mL,
      respectively. The B-I quadrant received only FA. The B-I quadrants of each rabbit
      conformed the FA group. The following 3 quadrants received the AFA in 10 MUg/mL,
      100 MUg/mL, and 1,000 MUg/mL, respectively. The occurrence of erythema and edema
      was recorded according to the Draize scoring system and the primary irritation
      index. After 72 hours, biopsies were performed. RESULTS: The AFA group presented
      significantly less erythema and edema compared to the FA group (P<0.05). The
      histopathologic evaluation at 72 hours showed normal characteristics in the APS
      group. CONCLUSION: Considering the clinical and histopathological signs, we
      conclude that the administration of the atomized extract of rhizome of C. longa,
      flowers of C. lutea, and leaves of A. muricata lacks antigenic effect but could
      have an antiallergenic effect in a model of dermal irritation in rabbits.

PMID- 27877048
TI  - Utilization of gastroprotective strategies for nonsteroidal anti-inflammatory
      drug-induced gastrointestinal events in a major teaching hospital.
AB  - BACKGROUND AND PURPOSE: Clinical guidelines recommend the prescribing of
      gastroprotective strategies in nonsteroidal anti-inflammatory drug (NSAID) users
      with risk factors for gastrointestinal (GI) ulcer or ulcer complications.
      However, these guidelines are not often translated into clinical practice.
      Therefore, the aim of this study was to investigate the utilization of
      gastroprotective strategies for NSAID-induced upper GI events in at-risk users in
      a major teaching hospital. PATIENTS AND METHODS: A cross-sectional,
      observational, pharmacy-based study was conducted in a major Asian institution
      with both primary and secondary health care services. This study involved the
      screening of prescriptions for regular NSAIDs, and patients who met the inclusion
      criteria were recruited and interviewed using a questionnaire. RESULTS: Of the
      409 participants recruited, 83.1% had at least one GI risk factor, of whom 70.3%
      did not receive appropriate gastroprotection. The most common GI risk factor was
      the use of high-dose NSAIDs (69.2%), followed by participants aged 65 years and
      older (22%) and concomitant use of low-dose aspirin (11.7%). Appropriate
      gastroprotective strategies utilized consisted of the use of a cyclooxygenase
      (COX)-2 inhibitor alone or a nonselective NSAID plus a proton pump inhibitor
      (PPI) in the moderate-risk group and a COX-2 inhibitor plus a PPI in the high
      risk group. Gastroprotective strategies were underutilized in 67.1% of at-risk
      participants and overutilized in 59.4% of those without risk factors. Co
      prescription of a histamine-2 receptor antagonist at lower-than-recommended doses
      constituted 59% of the inappropriate gastroprotective agents used. Logistic
      regression analysis revealed patients aged 65 years and older (odds ratio, 1.89;
      95% CI =1.15-3.09) as a predictor for the prescribing of gastroprotection by the
      clinicians. CONCLUSION: Approximately 70% of at-risk NSAID users, mainly on high
      dose NSAIDs, were not prescribed appropriate gastroprotective strategies. Further
      measures are warranted to improve the safe prescribing of regular NSAIDs.

PMID- 27877049
TI  - A review about biomarkers for the investigation of vascular function and
      impairment in diabetes mellitus.
AB  - The aim of this review was to analyze the main biomarkers of vascular function
      and impairment in patients with type 2 diabetes. Medline, SCOPUS, Web of Science,
      and Google Scholar databases were searched. We concluded that proatherogenic
      adhesion molecules (soluble intercellular adhesion molecule-1, soluble vascular
      adhesion molecule-1, and soluble E selectin) and inflammatory cytokines (high
      sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha)
      were elevated in type 2 diabetes mellitus. Their increased expression and release
      contribute to the accelerated atherogenesis typical of these patients. For these
      reasons, the early identification of high levels of these biomarkers will help to
      establish new strategies to reduce cardiovascular complications.

PMID- 27877051
TI  - Living with a sibling who suffers from an eating disorder: a pilot interview
      study.
AB  - BACKGROUND AND OBJECTIVE: Having a sibling who suffers from an eating disorder
      (ED) has a profound effect on healthy siblings' own health, quality of life and
      family relationships, yet siblings have been an excluded group within health
      care, and there is a lack of knowledge regarding healthy siblings' needs and
      wishes for information and support. Thus, the aim of this study was to examine
      adolescents' experiences of living with a sibling who suffers from an ED. METHOD:
      In this small-scale pilot study, three boys and two girls aged 15-20 years were
      interviewed, and the interviews were analyzed by qualitative content analysis.
      RESULTS: This study confirms prior knowledge of adolescents' experiences of
      living with a sibling who is suffering from an ED. The adolescents were concerned
      about their siblings and lacked information about their siblings' illness and
      treatment progress. The girls described that their everyday life had been heavily
      influenced by their sisters' illness, while the boys described that their
      everyday life with friends and activities were not affected to such a great
      extent. One new result that emerged as something positive was that some
      informants described that although the ED was a source of conflict in the family,
      it had led to greater awareness of the importance of gaining sufficient energy
      and had contributed to better meal situations in the family. CONCLUSION: Having a
      sibling with an ED had a profound and negative effect on family relationships,
      and was often a source of conflict, especially around mealtime. However, it
      appeared that if parents were able to organize family meals and create an open
      and supportive climate, the negative effects for the family could be reduced. The
      health care professionals need to acknowledge the siblings' need for information
      and support, and support parents in their important role of caring for well
      siblings.

PMID- 27877050
TI  - Development of proprotein convertase subtilisin/kexin type 9 inhibitors and the
      clinical potential of monoclonal antibodies in the management of lipid disorders.
AB  - The aim of this manuscript is to review available data to evaluate the present
      status of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the
      treatment of hypercholesterolemia. Relevant literature since 2003 is reviewed.
      The effectiveness of PCSK9 inhibitors in lowering low-density lipoprotein
      cholesterol and other atherogenic lipid fractions was studied in various Phase 2
      and Phase 3 trials of Alirocumab, Evolocumab, and Bococizumab. The results of
      published long-term ODYSSEY and OSLER studies are summarized. There have been
      three excellent meta-analysis studies on PCSK9 inhibitors which are outlined. The
      complex problem of cost-effectiveness was carefully evaluated by the Institute
      for Clinical and Economic Review (ICER). The draft report (ICER-2015) is
      summarized herewith. The cardiovascular outcome trials with Evolocumab (FOURIER),
      Alirocumab (ODYSSEY OUTCOME) and Bococizumab (SPIRE-1 and SPIRE-2) are the
      ongoing clinical trials, and their results are expected in 2017-2018. The search
      for new cost-effective analogs of PCSK9 inhibitors is ongoing.

PMID- 27877052
TI  - Dendritic cell immunotherapy versus bevacizumab plus irinotecan in recurrent
      malignant glioma patients: a survival gain analysis.
AB  - BACKGROUND: The bevacizumab and irinotecan protocol is considered a standard
      treatment regimen for recurrent malignant glioma. Recent advances in
      immunotherapy have hinted that vaccination with dendritic cells could become an
      alternative salvage therapy for the treatment of recurrent malignant glioma.
      METHODS: A search was performed on PubMed, Cochrane Library, Web of Science,
      ScienceDirect, and Embase in order to identify studies with patients receiving
      bevacizumab plus irinotecan or dendritic cell therapy for recurrent malignant
      gliomas. The data obtained from these studies were used to perform a systematic
      review and survival gain analysis. RESULTS: Fourteen clinical studies with
      patients receiving either bevacizumab plus irinotecan or dendritic cell
      vaccination were identified. Seven studies followed patients that received
      bevacizumab plus irinotecan (302 patients) and seven studies included patients
      that received dendritic cell immunotherapy (80 patients). For the patients who
      received bevacizumab plus irinotecan, the mean reported median overall survival
      was 7.5 (95% confidence interval [CI] 4.84-10.16) months. For the patients who
      received dendritic cell immunotherapy, the mean reported median overall survival
      was 17.9 (95% CI 11.34-24.46) months. For irinotecan + bevacizumab group, the
      mean survival gain was -0.02+/-2.00, while that for the dendritic cell
      immunotherapy group was -0.01+/-4.54. CONCLUSION: For patients with recurrent
      malignant gliomas, dendritic cell immunotherapy treatment does not have a
      significantly different effect when compared with bevacizumab and irinotecan in
      terms of survival gain (P=0.535) and does not improve weighted survival gain
      (P=0.620).

PMID- 27877055
TI  - miR-486-5p suppresses prostate cancer metastasis by targeting Snail and
      regulating epithelial-mesenchymal transition.
AB  - The most common cause of death from prostate cancer (PCa) is metastases. There is
      an increasing body of evidence that microRNAs play an important role in the
      development of PCa by regulating target genes involved in tumor metastasis. Here,
      we identified that expression of miR-486-5p was decreased in metastatic C4-2
      cells compared to non-metastatic LNCaP cells. Further validation in clinical
      samples showed that miR-486-5p expression was significantly decreased in
      metastatic PCa tissues compared to localized PCa tissues. Functional studies
      demonstrated that increased miR-486-5p expression can suppress cell migration and
      the invasive ability of C4-2 cells. Moreover, Snail, a key regulator of the
      epithelial-mesenchymal transition, was verified as a target gene of miR-486-5p.
      In conclusion, these findings suggest that miR-486-5p plays a suppressive role in
      mediating the migration and invasion of PCa by directly suppressing the protein
      expression of Snail and may provide a potential therapeutic target for the
      disease.

PMID- 27877054
TI  - Adefovir dipivoxil is less expensive than lamivudine and associated with similar
      prognosis in patients with hepatitis B virus-related hepatocellular carcinoma
      after radical resection.
AB  - AIM: Lamivudine (LAM) and adefovir dipivoxil (ADV) are widely used in patients
      with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), but few
      studies have directly compared their therapeutic efficacy and treatment cost.
      This study aims to compare LAM with ADV head-to-head in these patients. METHODS:
      We retrospectively analyzed 201 patients with HBV-related HCC who underwent
      radical resection and subsequently received LAM (n=155) or ADV (n=46). The two
      groups were compared in terms of HBV-DNA levels, liver function, antiviral
      resistance, recurrence-free, and overall survival, as well as antiviral
      medication costs. RESULTS: Despite significant improvement in HBV-DNA and alanine
      aminotransferase level in the LAM group after 1 year of antiviral therapy, these
      parameters did not differ significantly between the two groups over the following
      2 years. Incidence of antiviral resistance after 1, 2, and 3 years of antiviral
      treatment was significantly higher in the LAM group (19.5%, 45.7%, and 56.4%)
      than in the ADV group (0%, 3.3%, and 14.5%; P<0.001). Overall survival at 1, 2,
      and 3 years after resection was similar for the LAM group (84.5%, 69.3%, and
      64.6%) and the ADV group (84.1%, 77.8%, and 63.4%; P=0.905). Recurrence-free
      survival at the three follow-up points was also similar for the LAM group (71.7%,
      58.3%, and 43.9%) and the ADV group (81.1%, 66.1%, and 53.0%; P=0.452). Cox
      regression analysis confirmed that both nucleos(t)ide analogues were associated
      with similar overall and recurrence-free survival. However, the average
      medication costs after 1, 2, and 3 years of antiviral treatment were
      significantly higher in the LAM group (?3.0, ?4.8, and ?5.6 per person per day)
      than in the ADV group (?2.2, ?2.4, and ?3.1 per person per day; all P<0.05).
      CONCLUSION: ADV and LAM are associated with similar survival benefit in patients
      with HBV-related HCC after radical resection, but ADV is more cost-effective.

PMID- 27877053
TI  - Synergistic activity of vorinostat combined with gefitinib but not with sorafenib
      in mutant KRAS human non-small cell lung cancers and hepatocarcinoma.
AB  - Development of drug resistance limits the efficacy of targeted therapies.
      Alternative approaches using different combinations of therapeutic agents to
      inhibit several pathways could be a more effective strategy for treating cancer.
      The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine
      kinase inhibitor (gefitinib) or a multi-targeted kinase inhibitor (sorafenib) in
      combination with a histone deacetylase inhibitor (vorinostat) on cell
      proliferation, cell cycle distribution, apoptosis, and signaling pathway
      activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type
      EGFR and mutant KRAS were investigated. The effects of the synergistic drug
      combinations were also studied in human lung adenocarcinoma and hepatocarcinoma
      cells in vivo. The combination of gefitinib and vorinostat synergistically
      reduced cell growth and strongly induced apoptosis through inhibition of the
      insulin-like growth factor-1 receptor/protein kinase B (IGF-1R/AKT)-dependent
      signaling pathway. Moreover, the gefitinib and vorinostat combination strongly
      inhibited tumor growth in mice with lung adenocarcinoma or hepatocarcinoma tumor
      xenografts. In contrast, the combination of sorafenib and vorinostat did not
      inhibit cell proliferation compared to a single treatment and induced G2/M cell
      cycle arrest without apoptosis. The sorafenib and vorinostat combination
      sustained the IGF-1R-, AKT-, and mitogen-activated protein kinase-dependent
      signaling pathways. These results showed that there was synergistic cytotoxicity
      when vorinostat was combined with gefitinib for both lung adenocarcinoma and
      hepatocarcinoma with mutant KRAS in vitro and in vivo but that the combination of
      vorinostat with sorafenib did not show any benefit. These findings highlight the
      important role of the IGF-1R/AKT pathway in the resistance to targeted therapies
      and support the use of histone deacetylase inhibitors in combination with EGFR
      tyrosine kinase inhibitors, especially for treating patients with mutant KRAS
      resistant to other treatments.

PMID- 27877056
TI  - A retrospective analysis of the clinicopathological and molecular characteristics
      of pulmonary blastoma.
AB  - PURPOSE: The aim of this study was to analyze and summarize the
      clinicopathological and molecular characteristics of classic biphasic pulmonary
      blastoma (PB) to improve its diagnosis and treatment. PATIENTS AND METHODS: A
      retrospective analysis was performed in patients who were diagnosed with PB at
      Sun Yat-Sen University Cancer Center from March 1995 to March 2015. Genomic DNA
      was profiled using a capture-based targeted sequencing panel. RESULTS: Sixteen
      patients with an average age of 40 years were included in this study. Accurate
      preoperative diagnosis was very challenging as surgically resected tissues with
      immunohistochemical staining were required for the diagnosis. Surgery was the
      optimal treatment for localized disease and there was no standard management for
      metastatic disease. Mutations were detected among 9 out of the 56 genes profiled,
      including BRCA2, ERBB4, ALK, MET, BRAF, RAF1, PTEN, EGFR, and PIK3CA. CONCLUSION:
      Due to the low incidence rate and the reclassification of PB, no standard
      treatment is available. Although the numbers of cases are few with varying
      individual experiences, it is important to improve our understanding regarding
      this rare lung cancer. Targeted DNA sequencing may be of clinical use for
      molecular testing and the effects of targeted therapy need to be confirmed.

PMID- 27877057
TI  - Chronic sphenoid rhinosinusitis: management challenge.
AB  - Chronic sphenoid rhinosinusitis is a spectrum of inflammatory diseases in
      isolated sphenoid sinus which may persist over a period of 12 weeks. It is a
      different entity from other types of rhinosinusitis because clinical
      presentations include headache, visual loss or diplopia, and patients may or may
      not have nasal obstruction or nasal discharge. Nasal endoscopic examination is
      useful, and computed tomography is mandatory. The disease requires comprehensive
      knowledge and appropriate imaging technique for diagnosis. To treat patients with
      chronic sphenoid rhinosinusitis, surgical treatment with endoscopic transnasal
      sphenoidotomy is often required. As there are no recent updated reviews of
      chronic sphenoid rhinosinusitis, in this article, we review the anatomy of the
      sphenoid sinus and its clinical relationship with the clinical signs and symptoms
      of the disease, the imaging findings of each diagnosis and the comprehensive
      surgical techniques.

PMID- 27877058
TI  - Teneligliptin real-world efficacy assessment of type 2 diabetes mellitus patients
      in India (TREAT-INDIA study).
AB  - BACKGROUND AND AIMS: Teneligliptin was introduced in India in May 2015. It has
      gained popularity and is already widely prescribed in type 2 diabetes mellitus
      (T2DM). This "real life" data collection was conducted to assess the efficacy of
      teneligliptin in Indian T2DM patients. METHODS: Predesigned structured proforma
      was used to collect information from the prescribing physicians regarding the
      efficacy of teneligliptin when prescribed as monotherapy as well as combination
      therapy with other antidiabetic drugs in T2DM patients. Information on the
      glycemic parameters at baseline prior to starting teneligliptin and at the end of
      3 months therapy was collected. The efficacy was assessed by analyzing the mean
      change in 3-month values of glycosylated hemoglobin (HbA1c), fasting plasma
      glucose (FPG), and postprandial plasma glucose (PPG). RESULTS: Data of 4305
      patients was available for analysis. There was statistically significant
      improvement in mean HbA1c, FPG, and PPG with teneligliptin therapy. Means changes
      in HbA1c, FPG, and PPG were -1.37%+/-1.15%, 51.29+/-35.41 mg/dL, and 80.89+/
      54.27 mg/dL, respectively. Subgroup analysis revealed that HbA1c (%) reduction
      with teneligliptin when used as monotherapy, add-on to metformin or add-on to
      metformin plus sulfonylureas combination, add-on to metformin plus alpha
      glucosidase inhibitor combination or add-on to insulin was 0.98+/-0.53, 1.07+/
      0.83, 1.46+/-1.33, 1.43+/-0.80, and 1.55+/-1.05, respectively. CONCLUSION: Real
      world data suggests that teneligliptin significantly improves glycemic control in
      Indian patients with T2DM when prescribed either as monotherapy or as an add-on
      to one or more other commonly prescribed antidiabetic drugs.

PMID- 27877059
TI  - Skin rejuvenation using cosmetic products containing growth factors, cytokines,
      and matrikines: a review of the literature.
AB  - Skin aging is primarily due to alterations in the dermal extracellular matrix,
      especially a decrease in collagen I content, fragmentation of collagen fibrils,
      and accumulation of amorphous elastin material, also known as elastosis. Growth
      factors and cytokines are included in several cosmetic products intended for skin
      rejuvenation because of their ability to promote collagen synthesis. Matrikines
      and matrikine-like peptides offer the advantage of growth factor-like activities
      but better skin penetration due to their much smaller molecular size. In this
      review, we summarize the commercially available products containing growth
      factors, cytokines, and matrikines for which there is evidence that they promote
      skin rejuvenation.

PMID- 27877060
TI  - Anti-inflammatory and immunomodulatory effects of Aquaphilus dolomiae extract on
      in vitro models.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common skin disease characterized by
      recurrent pruritic inflammatory skin lesions resulting from structural and immune
      defects of the skin barrier. Previous studies have shown the clinical efficacy of
      Avene thermal spring water in AD, and a new microorganism, Aquaphilus dolomiae
      was suspected to contribute to these unique properties. The present study
      evaluated the anti-inflammatory, antipruritic, and immunomodulatory properties of
      ES0, an original biological extract of A. dolomiae, in immune and inflammatory
      cell models in order to assess its potential use in the treatment of AD.
      MATERIALS AND METHODS: An ES0 extract containing periplasmic and membrane
      proteins, peptides, lipopolysaccharides, and exopolysaccharides was obtained from
      A. dolomiae. The effects of the extract on pruritus and inflammatory mediators
      and immune mechanisms were evaluated by using various AD cell models and assays.
      RESULTS: In a keratinocyte model, ES0 inhibited the expression of the
      inflammatory mediators, thymic stromal lymphopoietin, interleukin (IL)-18, IL-4R,
      IL-8, monocyte chemoattractant protein-3, macrophage inflammatory protein-3alpha,
      and macrophage-derived chemokine and induced the expression of involucrin, which
      is involved in skin barrier keratinocyte terminal differentiation. In addition,
      ES0 inhibited protease-activated receptor-2 activation in HaCaT human
      keratinocytes stimulated by stratum corneum tryptic enzyme and T helper type (Th)
      1, Th2, and Th17 cytokine production in Staphylococcal enterotoxin B-stimulated
      CD4+ lymphocytes. Lastly, ES0 markedly activated innate immunity through toll
      like receptor (TLR) 2, TLR4, and TLR5 activation (in recombinant human embryonic
      kidney 293 cells) and through antimicrobial peptide induction (psoriasin, human
      beta-defensin-2, and cathelicidin), mainly through TLR5 activation (in normal
      human keratinocytes). CONCLUSION: Overall, these in vitro results confirm the
      marked regulatory activity of this A. dolomiae extract on inflammatory and immune
      responses, which may be of value by virtue of its potential as an adjunctive
      treatment of AD inflammatory and pruritic lesions.

PMID- 27877061
TI  - Aloe sterol supplementation improves skin elasticity in Japanese men with
      sunlight-exposed skin: a 12-week double-blind, randomized controlled trial.
AB  - BACKGROUND/OBJECTIVE: Recently, it was confirmed that the daily oral intake of
      plant sterols of Aloe vera gel (Aloe sterol) significantly increases the skin
      barrier function, moisture, and elasticity in photoprotected skin. This study
      aimed to investigate whether Aloe sterol intake affected skin conditions
      following sunlight exposure in Japanese men. METHODS: We performed a 12-week,
      randomized, double-blind, placebo-controlled study to evaluate the effects of
      oral Aloe sterol supplementation on skin conditions in 48 apparently healthy men
      (age range: 30-59 years; average: 45 years). The subjects were instructed to
      expose the measurement position of the arms to the sunlight outdoors every day
      for 12 weeks. The skin parameters were measured at 0 (baseline), 4, 8, and 12
      weeks. RESULTS: Depending on the time for the revelation of the sunlight, the b*
      value and melanin index increased and the skin moisture decreased. After taking
      an Aloe sterol tablet daily for 12 weeks, the skin elasticity index (R2, R5, and
      R7) levels were significantly higher than the baseline value. There were no
      differences between the groups in these skin elasticity values. In the subgroup
      analysis of subjects aged <46 years, the change in the R5 and R7 was
      significantly higher in the Aloe group than in the placebo group at 8 weeks
      (P=0.0412 and P=0.0410, respectively). There was a difference in the quantity of
      sun exposure between each subject, and an additional clinical study that
      standardizes the amount of ultraviolet rays is warranted. No Aloe sterol intake
      dependent harmful phenomenon was observed during the intake period. CONCLUSION:
      Aloe sterol ingestion increased skin elasticity in the photodamaged skin of men
      aged <46 years.

PMID- 27877062
TI  - Systemic abnormalities of psoriatic patients: a retrospective study.
AB  - BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory disease related
      to the metabolic syndrome, cardiovascular disease, and other comorbidities.
      However, so far there has been no specific research concerning systemic
      abnormalities in psoriatic patients. OBJECTIVE: A retrospective study was
      conducted focusing on the detailed systemic abnormalities in psoriatic patients.
      METHODS: Psoriatic inpatients data was collected from July 2009 to September
      2015. The inclusion criteria were first-time hospitalization and without
      administration of systemic drug therapy or exposure to phototherapy for psoriasis
      for at least 1 month. Detailed systemic indexes were mainly evaluated. RESULTS:
      The abnormality rates of blood routine examination, urine examination, blood
      biochemical examination and chest X-ray of 43 psoriatic patients were
      significantly higher than those of 44 non-psoriasis controls, and psoriasis
      patients significantly had higher absolute values of leukocytes and neutrophils,
      and significantly lower values of lymphocytes. Compared with psoriasis vulgaris,
      erythrodermic psoriasis had significantly higher abnormality rates of blood
      biochemical examination and serum electrolyte analysis. Erythrodermic psoriasis
      had significantly higher absolute values of blood leukocytes, neutrophils, and
      lower serum calcium compared with those of psoriasis vulgaris. The neutrophil-to
      lymphocyte ratio of controls was significantly lower than that of psoriatic
      patients, and neutrophil-to-lymphocyte ratio of erythrodermic psoriasis was
      significantly higher in comparison with psoriasis vulgaris. CONCLUSION: This
      study is the first report in relation to a detailed assessment of systemic
      abnormalities in psoriatic patients prior to onset of systemic treatment. The
      systemic condition of psoriatic patients should be observed by clinicians before
      systemic therapy.

PMID- 27877063
TI  - COPD patients' medical care and support in Greece during financial crisis.
AB  - BACKGROUND: The need to follow a multidisciplinary strategy in chronic
      obstructive pulmonary disease (COPD) management and rehabilitation in community
      settings in Greece raises significant questions, given the severe austerity
      measures being imposed at present. The aim of this study was to investigate the
      clinical profile of patients with COPD along with the care provided in rural
      community settings in Greece. METHODS: Two primary health care centers and 200
      newly diagnosed patients over a 12-month period were involved in the study. A
      self-assessment questionnaire, including questions about smoking habits, the
      presence of comorbidities and chronic respiratory symptoms, as well as the COPD
      Assessment Test were used. Spirometry was performed with a dry spirometer.
      Obstructive spirometry was defined as forced expiratory volume in 1 second/forced
      vital capacity ratio <0.7, according to Global Initiative for Chronic Obstructive
      Lung Disease guidelines. RESULTS: Males comprised 70% of the sample, with cough
      and sputum being the prominent signs. Regarding COPD staging, 68.5% were
      classified in stages I/II. Arterial hypertension and coronary heart disease were
      the most common comorbidities. Current smokers accounted for 88.5%, while 88%
      were heavy drinkers. A general practitioner made the diagnosis in 68.5% of the
      cases, among which offspring and spouses provided home care in 38% and 8% of the
      cases, respectively, while an informal caregiver other than a relative was
      reported in 34% of the cases. No caregiver (self-care) was reported in 20% of the
      cases. All patients of stage III and IV had a COPD Assessment Test score >10.
      CONCLUSION: Patients with COPD dwelling in the community exhibit an overall mild
      to-moderate type of COPD. General practitioner is in charge of COPD management.
      Informal caregiving is the major type of home care, with nonfamily members
      playing a significant role. The patients' profile permits limited optimism about
      their future perspective and urges for immediate action at primary care level.

PMID- 27877064
TI  - Low back pain in older adults - the need for specific outcome and psychometric
      tools.

PMID- 27877065
TI  - Poor adhesion of fentanyl transdermal patches may mimic end-of-dosage failure
      after 48 hours and prompt early patch replacement in hospitalized cancer pain
      patients.
AB  - CONTEXT: Renewal of fentanyl transdermal patch (transdermal therapeutic system
      [TTS]) should occur every 3 days (72 hours) according to manufacturer's
      guidelines. Some studies mentioned patients reporting end-of-dose failure, and
      thus, some authors recommend shortening the interval of application to 2 days (48
      hours). However, reasons for early replacement are mostly unknown. OBJECTIVES:
      The objectives of this study were to assess the prevalence of early replacement
      of fentanyl TTS in a cancer center in Basel, Switzerland, and to assess the
      reasons for early replacement in stationary patients. METHODS: We retrieved all
      fentanyl TTS administered in a cancer center in Basel, Switzerland, between
      November 11, 2011, and January 31, 2015, from the electronic medical database.
      RESULTS: A total of 739 patients (mean age 71.4+/-11.5 years, 55% women) were
      administered 2,250 fentanyl TTS (dosage 6-500 ug/hour). Most replacements
      occurred after 72 hours (61.6%) and a few after 48 hours (7.4%). Patients with
      early replacement after 48 hours were significantly younger (63.8 years versus
      71.5 years, p<0.001) and obtained higher mean dosages of fentanyl TTS (89 ug/hour
      versus 44.1 ug/hour, p<0.001) and rescue medication (calculated as oral morphine
      equivalent in milligrams: 185.1 mg versus 39.6 mg during the first 24 hours after
      replacement, p<0.001). No pharmacological rationale for early replacement was
      observed. According to 57 physicians, nurses, and pharmacists, the most often
      reasons for early TTS replacement were end-of-dosage pain (41.4%) and poor
      adhesion (31.4%). CONCLUSION: In the absence of any physiological,
      pharmacological, or environmental reasons recorded in the database to explain an
      early replacement of fentanyl TTS, skin adhesion problems may point practical
      reasons and mimic end-of-dosage failure.

PMID- 27877066
TI  - Implantation of permanent pleural catheter for palliation of malignant pleural
      effusion.
AB  - PURPOSE: Malignant pleural effusion (MPE) is a disabling condition caused in most
      instances by far-advanced cancer. The treatment is palliative and should ideally
      be minimally invasive. The aim of this retrospective study was to evaluate the
      effectiveness of implantation of a permanent PleurX catheter in the treatment of
      recurrent MPE in patients with terminal cancer disease. PATIENTS AND METHODS:
      Eighteen consecutive patients with terminal cancer and MPE, who had a permanent
      PleurX catheter implanted in the period from February 2014 to August 2015, were
      retrospectively evaluated. Medical records were reviewed for data on procedures
      and patients. RESULTS: Twenty-two PleurX catheters were implanted in the pleural
      cavity of 18 patients. The technical success rate was 100%. All patients had
      relief of symptoms. Catheter patency was 91%. Six patients experienced minor
      adverse events (AEs) and two patients experienced moderate-to-severe AEs. The
      median survival time for the 14 patients who died during follow-up was 45 days.
      CONCLUSION: Implantation of a permanent PleurX catheter is a safe procedure with
      a high success rate and only few AEs. The procedure has the potential to serve as
      an effective procedure for palliation of recurrent MPE in terminal cancer
      patients.

PMID- 27877067
TI  - Similar long-term survival of consecutive in-hospital and out-of-hospital cardiac
      arrest patients treated with targeted temperature management.
AB  - OBJECTIVE: The long-term survival of in-hospital cardiac arrest (IHCA) patients
      treated with targeted temperature management (TTM) is poorly described. The aim
      of this study was to compare the outcomes of consecutive IHCA with out-of
      hospital cardiac arrest (OHCA) patients treated with TTM. DESIGN SETTING AND
      PATIENTS: Retrospectively collected data on all consecutive adult patients
      treated with TTM at a university tertiary heart center between 2005 and 2011 were
      analyzed. MEASUREMENTS: Primary endpoints were survival to hospital discharge and
      long-term survival. Secondary endpoint was neurological outcome assessed using
      the Pittsburgh cerebral performance category (CPC). RESULTS: A total of 282
      patients were included in this study; 233 (83%) OHCA and 49 (17%) IHCA. The IHCA
      group presented more often with asystole, received bystander cardiopulmonary
      resuscitation (CPR) in all cases, and had shorter time to return of spontaneous
      circulation (ROSC). Survival to hospital discharge was 54% for OHCA and 53% for
      IHCA (adjusted odds ratio 0.98 [95% confidence interval {CI}; 0.43-2.24]). Age
      <=60 years, bystander CPR, time to ROSC <=10 min, and shockable rhythm at
      presentation were associated with survival to hospital discharge. Good neurologic
      outcome among survivors was achieved by 86% of OHCA and 92% of IHCA (P=0.83).
      After a median follow-up time of >5 years, 83% of OHCA and 77% of IHCA were alive
      (adjusted hazard ratio [HR] 1.51 [95% CI; 0.59-3.91]). Age <=60 years was the
      only factor associated with long-term survival (adjusted HR 2.73 [95% CI; 1.36
      5.52]). CONCLUSION: There was no difference in short- and long-term survival and
      no difference in neurologic outcome to hospital discharge between IHCA and OHCA
      patients treated with TTM despite higher frequency of asystole in IHCA.

PMID- 27877069
TI  - Risk factors and mortality associated with undertriage at a level I safety-net
      trauma center: a retrospective study.
AB  - PURPOSE: The primary objective of this study was to determine the risk factors
      associated with undertriage and the risk factors for mortality among the
      undertriaged patients at a level I safety-net trauma center. METHODS: A
      retrospective analysis was performed of all trauma patients who presented to a
      level I safety-net trauma center with an injury severity score >15 over a 2-year
      period (2013-2014). Univariate and multivariate regression analyses were used to
      determine the risk factors predictive of undertriage in major trauma patients
      (injury severity score >15) and of mortality in undertriaged patients. RESULTS:
      During the 2-year study period, 334 of 2,485 admitted trauma patients presented
      with major trauma and were included in our study. From the univariate analysis,
      variables that were found to be independently associated with mortality in
      undertriaged patients included intubation, Glasgow Coma Scale score, revised
      trauma score, and dementia. Independent risk factors that were found to be
      significantly associated with undertriage in severely injured trauma patients
      included Glasgow Coma Scale score, motor vehicle crash, falls, revised trauma
      score, systolic blood pressure, heart rate, intubation, and dementia. When a
      multivariate analysis was performed to evaluate the statistically significant
      risk factors, dementia was found to be significantly associated with undertriage
      in severely injured trauma patients. CONCLUSION: Severely injured trauma patients
      with dementia are at significant risk for undertriage. Early identification of
      these risk factors while triaging at a level I safety-net trauma center could
      translate into improved patient outcomes following severe trauma.

PMID- 27877068
TI  - Comparative study of minimal fresh gas flow used in Lack-Plus and Lack's circuit
      in spontaneously breathing anesthetized adults.
AB  - BACKGROUND: The Lack's circuit is a co-axial Mapleson A breathing system commonly
      used in spontaneously breathing anesthetized adults but still requires high fresh
      gas flow (FGF). The Lack-Plus circuit was invented with the advantage of lower
      FGF requirement. The authors compared the Lack-Plus and Lack's circuit for the
      minimal FGF requirement with no rebreathing in spontaneously breathing
      anesthetized adults. METHODS: This was a randomized crossover study. We enrolled
      24 adult patients undergoing supine elective surgery, with a body mass index <=30
      kg/m2 and an American Society of Anesthesiologists physical status I-II. They
      were randomly allocated to group 1 (LP-L) starting with Lack-Plus then switching
      to Lack's circuit or group 2 (L-LP) (with the reverse pattern). After induction
      and intubation, anesthesia was maintained with 50% N2O/O2 and desflurane (4%-6%)
      plus fentanyl titration to maintain an optimal respiratory rate between 10 and
      16/min. Starting with the first circuit, all the patients were spontaneously
      breathing with a FGF of 4 L/min for 10 min, gradually decreased by 0.5 L/min
      every 5 min until FGF was 2.5 L/min. End-tidal CO2, inspired minimum CO2 (ImCO2),
      mean arterial pressure, and oxygen saturation were recorded until rebreathing
      (ImCO2 >0 mmHg) occurred. The alternate anesthesia breathing circuit was used and
      the measurements were repeated. RESULTS: The respective minimal FGF at the point
      of rebreathing for the Lack-Plus and Lack's circuit was 2.7+/-0.8 and 3.3+/-0.5
      L/min, respectively, p<0.001. At an FGF of 2.5 L/min, the respective ImCO2 was
      1.5+/-2.0 and 4.2+/-2.6 mmHg, respectively, p<0.001. CONCLUSION: The Lack-Plus
      circuit can be used safely and effectively, and it requires less FGF than Lack's
      circuit in spontaneously breathing anesthetized adults.

PMID- 27877070
TI  - Aerobic power and lean mass are indicators of competitive sprint performance
      among elite female cross-country skiers.
AB  - The purpose of this study was to establish the optimal allometric models to
      predict International Ski Federation's ski-ranking points for sprint competitions
      (FISsprint) among elite female cross-country skiers based on maximal oxygen
      uptake ( [Formula: see text]) and lean mass (LM). Ten elite female cross-country
      skiers (age: 24.5+/-2.8 years [mean +/- SD]) completed a treadmill roller-skiing
      test to determine [Formula: see text] (ie, aerobic power) using the diagonal
      stride technique, whereas LM (ie, a surrogate indicator of anaerobic capacity)
      was determined by dual-emission X-ray anthropometry. The subjects' FISsprint were
      used as competitive performance measures. Power function modeling was used to
      predict the skiers' FISsprint based on [Formula: see text], LM, and body mass.
      The subjects' test and performance data were as follows: [Formula: see text],
      4.0+/-0.3 L min-1; LM, 48.9+/-4.4 kg; body mass, 64.0+/-5.2 kg; and FISsprint,
      116.4+/-59.6 points. The following power function models were established for the
      prediction of FISsprint: [Formula: see text] and 6.95 * 1010 . LM-5.25; these
      models explained 66% (P=0.0043) and 52% (P=0.019), respectively, of the variance
      in the FISsprint. Body mass failed to contribute to both models; hence, the
      models are based on [Formula: see text] and LM expressed absolutely. The results
      demonstrate that the physiological variables that reflect aerobic power and
      anaerobic capacity are important indicators of competitive sprint performance
      among elite female skiers. To accurately indicate performance capability among
      elite female skiers, the presented power function models should be used. Skiers
      whose [Formula: see text] differs by 1% will differ in their FISsprint by 5.8%,
      whereas the corresponding 1% difference in LM is related to an FISsprint
      difference of 5.1%, where both differences are in favor of the skier with higher
      [Formula: see text] or LM. It is recommended that coaches use the absolute
      expression of these variables to monitor skiers' performance-related training
      adaptations linked to changes in aerobic power and anaerobic capacity.

PMID- 27877071
TI  - The SWEET SPOTS study: a real-world interpretation of the 2012 American Diabetes
      Association Position Statement regarding individualized A1C targets.
AB  - OBJECTIVE: To evaluate awareness of the 2012 American Diabetes Association (ADA)
      Position Statement among physicians and assess its effects on patient-centered
      glycated hemoglobin (A1C) goals in the management of type 2 diabetes (T2D).
      RESEARCH DESIGN AND METHODS: The Summarizing Real-World Individualized TrEatmEnT
      GoalS and Potential SuppOrT Systems in Type 2 Diabetes (SWEET SPOTS) study used
      the HealthCore claims database to identify T2D patients, stratified by risk, and
      their treating physicians to assess primary care physician and endocrinologist
      awareness of the 2012 ADA Position Statement. Physicians completed online surveys
      on A1C targets before and after receiving an educational intervention to review
      the position statement. RESULTS: Of 125 responding physicians (mean age 50.3
      years, 12.8% endocrinologists) who were linked to 125 patient profiles (mean age
      56.9 years, 42% female, mean A1C 7.2%), 92% were at least somewhat aware of the
      position statement prior to the intervention and 59% believed that the statement
      would impact how they set A1C targets. The educational intervention resulted in
      mostly less stringent goal setting for both lower and higher risk patients, but
      changes were not significant. The proportion of physician-assigned A1C targets
      within ADA-recommended ranges increased from 56% to 66% post-intervention
      (P<0.0001). CONCLUSION: Physicians treating T2D are aware of the 2012 ADA
      Position Statement and believe that it may influence treatment goals. While
      patient-specific A1C targets were not significantly impacted, physicians
      indicated that they would make targets more or less stringent for lower and
      higher risk patients, respectively, across their practice. Further research into
      optimizing physician education regarding individualized A1C targets is warranted.

PMID- 27877073
TI  - Ocimum gratissmum aqueous extract reduces plasma lipid in hypercholesterol-fed
      hamsters.
AB  - Objectives: Hyperlipidemia is a significant risk factor in the development of
      atherosclerosis and related diseases which are major health problem in many
      developed and developing countries that can lead to fatality due to the changes
      in lifestyle and dietary habits in this modern age. Methods: In the present
      study, the Ocimum gratissimum aqueous extract (OGE) was tested for the lowering
      effect on the serum lipid level of male hamsters on a high-fat (12%) and high
      cholesterol (0.2%) diet (HFCD). Results: The results showed that the levels of
      serum high-density-lipoprotein-cholesterol (HDL-C) low-density-lipoprotein
      cholesterol (LDL-C), total cholesterol (TC), and triglycerols (TG) were increased
      in the HFCD group (113+/-11, 259+/-87, 629+/-175 and 625+/-262, respectively), as
      compared to the control normal diet group (51+/-8, 19+/-5, 77+/-16 and 101+/-44,
      respectively). When co-treated with various doses (10 and 20 mg/kg) of the OGE or
      rosuvastatin, the rats exhibited the restoration of normal serum LDL-C, TC, and
      TG levels. Conclusion: Therefore, we suggest that the Ocimum gratissimum aqueous
      extract may have the potential function of lowering serum lipid in rats.

PMID- 27877072
TI  - Cultured Human Periosteum-Derived Cells Can Differentiate into Osteoblasts in a
      Perioxisome Proliferator-Activated Receptor Gamma-Mediated Fashion via Bone
      Morphogenetic Protein signaling.
AB  - The differentiation of mesenchymal stem cells towards an osteoblastic fate
      depends on numerous signaling pathways, including activation of bone
      morphogenetic protein (BMP) signaling components. Commitment to osteogenesis is
      associated with activation of osteoblast-related signal transduction, whereas
      inactivation of this signal transduction favors adipogenesis. BMP signaling also
      has a critical role in the processes by which mesenchymal stem cells undergo
      commitment to the adipocyte lineage. In our previous study, we demonstrated that
      an agonist of the perioxisome proliferator-activated receptor gamma (PPARgamma),
      a master regulator of adipocyte differentiation, stimulates osteoblastic
      differentiation of cultured human periosteum-derived cells. In this study, we
      used dorsomorphin, a selective small molecule inhibitor of BMP signaling, to
      investigate whether BMP signaling is involved in the positive effects of
      PPARgamma agonists on osteogenic phenotypes of cultured human periosteum-derived
      cells. Both histochemical detection and bioactivity of ALP were clearly increased
      in the periosteum-derived cells treated with the PPARgamma agonist at day 10 of
      culture. Treatment with the PPARgamma agonist also caused an increase in alizarin
      red S staining and calcium content in the periosteum-derived osteoblasts at 2 and
      3 weeks of culture. In contrast, dorsomorphin markedly decreased ALP activity,
      alizarin red S staining and calcium content in both the cells treated with
      PPARgamma agonist and the cells cultured in osteogenic induction media without
      PPARgamma agonist during the culture period. In addition, the PPARgamma agonist
      clearly increased osteogenic differentiation medium-induced BMP-2 upregulation in
      the periosteum-derived osteoblastic cells at 2 weeks of culture as determined by
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR),
      immunoblotting, and immunocytochemical analyses. Although further study will be
      needed to clarify the mechanisms of PPARgamma-regulated osteogenesis, our results
      suggest that the positive effects of a PPARgamma agonist on the osteogenic
      phenotypes of cultured human periosteum-derived cells seem to be dependent on BMP
      signaling.

PMID- 27877074
TI  - Association between Benzodiazepine Use and Dementia: Data Mining of Different
      Medical Databases.
AB  - Purpose: Some studies have suggested that the use of benzodiazepines in the
      elderly is associated with an increased risk of dementia. However, this
      association might be due to confounding by indication and reverse causation. To
      examine the association between benzodiazepine anxiolytic drug use and the risk
      of dementia, we conducted data mining of a spontaneous reporting database and a
      large organized database of prescriptions. Methods: Data from the US Food and
      Drug Administration Adverse Event Reporting System (FAERS) from the first quarter
      of 2004 through the end of 2013 and data from the Canada Vigilance Adverse
      Reaction Online Database from the first quarter of 1965 through the end of 2013
      were used for the analyses. The reporting odds ratio (ROR) and information
      component (IC) were calculated. In addition, prescription sequence symmetry
      analysis (PSSA) was performed to identify the risk of dementia after using
      benzodiazepine anxiolytic drugs over the period of January 2006 to May 2014.
      Results: Benzodiazepine use was found to be associated with dementia in analyses
      using the FAERS database (ROR: 1.63, 95% CI: 1.61-1.64; IC: 0.66, 95% CI: 0.65
      0.67) and the Canada Vigilance Adverse Reaction Online Database (ROR: 1.88, 95%
      CI: 1.83-1.94; IC: 0.85, 95% CI: 0.80-0.89). ROR and IC values increased with the
      duration of action of benzodiazepines. In the PSSA, a significant association was
      found, with adjusted sequence ratios of 1.24 (1.05-1.45), 1.20 (1.06-1.37), 1.23
      (1.11-1.37), 1.34 (1.23-1.47), 1.41 (1.29-1.53), and 1.44 (1.33-1.56) at
      intervals of 3, 6, 12, 24, 36, and 48 months, respectively. Furthermore, the
      additional PSSA, in which patients who initiated a new treatment with
      benzodiazepines and anti-dementia drugs within 12- and 24-month periods were
      excluded from the analysis, demonstrated significant associations of
      benzodiazepine use with dementia risk. Conclusion: Multi-methodological
      approaches using different methods, algorithms, and databases suggest that long
      term use of benzodiazepines and long-acting benzodiazepines are strongly
      associated with an increased risk of dementia.

PMID- 27877075
TI  - The Limbal Epithelial Progenitors in the Limbal Niche Environment.
AB  - Limbal epithelial progenitors are stem cells located in limbal palisades of vogt.
      In this review, we present the audience with recent evidence that limbal
      epithelial progenitors may be a powerful stem cell resource for the cure of human
      corneal stem cell deficiency. Further understanding of their mechanism may shed
      lights to the future successful application of stem cell therapy not only to the
      eye tissue, but also to the other tissues in the human body.

PMID- 27877076
TI  - Cardiomyogenic Differentiation of Human Dental Follicle-derived Stem Cells by
      Suberoylanilide Hydroxamic Acid and Their In Vivo Homing Property.
AB  - The purpose of the present study was to investigate the in vitro cardiomyogenic
      differentiation potential of human dental follicle-derived stem cells (DFCs)
      under the influence of suberoylanilide hydroxamic acid (SAHA), a member of the
      histone deacetylase inhibitor family, and analyze the in vivo homing capacity of
      induced cardiomyocytes (iCMs) when transplanted systemically. DFCs from extracted
      wisdom teeth showed mesenchymal stem cell (MSC) characteristics such as plate
      adherent growing, expression of MSC markers (CD44, CD90, and CD105), and
      mesenchymal lineage-specific differentiation potential. Adding SAHA to the
      culture medium induced the successful in vitro differentiation of DFCs into
      cardiomyocytes. These iCMs expressed cardiomyogenic markers, including alpha
      smooth muscle actin (alpha-SMA), cardiac muscle troponin T (TNNT2), Desmin, and
      cardiac muscle alpha actin (ACTC1), at both the mRNA and protein level. For the
      assessment of homing capacity, PKH26 labeled iCMs were intraperitoneally injected
      (1*106 cells in 100 uL of PBS) into the experimental mice, and the ratios of
      PKH26 positive cells to the total number of injected cells, in multiple organs
      were determined. The calculated homing ratios, 14 days after systemic cell
      transplantation, were 5.6 +/- 1.0%, 3.6 +/- 1.1%, and 11.6 +/- 2.7% in heart,
      liver, and kidney respectively. There was no difference in the serum levels of
      interleukin-2 and interleukin-10 at 14 days after transplantation, between the
      experimental (iCM injected) and control (no injection or PBS injection) groups.
      These results demonstrate that DFCs can be an excellent source for cardiomyocyte
      differentiation and regeneration. Moreover, the iCMs can be delivered into heart
      muscle via systemic administration without eliciting inflammatory or immune
      response. This can serve as the pilot study for further investigations into the
      in vitro cardiomyogenic differentiation potential of DFCs under the influence of
      SAHA and the in vivo homing capacity of the iCMs into the heart muscle, when
      injected systemically.

PMID- 27877077
TI  - Amelioration of estrogen deficiency-induced obesity by collagen hydrolysate.
AB  - Objectives: Menopausal transition with declining estrogen levels significantly
      affects the physiological properties of women and consequently contributes to a
      series of medical conditions, including obesity. Obesity is a crucial risk factor
      associated with cardiovascular diseases, diabetes mellitus, and breast cancer.
      Increasing dietary protein content improves satiety and energy expenditure. Thus,
      we hypothesize that supplementing with collagen, a common dietary protein, may
      alleviate menopause-induced obesity. Methods: We used ovariectomized (OVX) rats
      to mimic a menopausal human. The body weight of OVX rats significantly increased
      compared with that of sham-operated rats (P<0.05), but uterus weight was
      decreased. Adipocyte size in perigonadal adipose tissue also increased (P<0.05).
      Results: By contrast, OVX rats supplemented with aqueous collagen hydrolysate
      (2.5 mg/mL) exhibited significant attenuation in body weight gain and adipocyte
      enlargement (P<0.05), but insignificant change in uterus weight. Further
      investigation indicated that collagen hydrolysate supplementation insignificantly
      affected the levels of dorsal fat, serum total cholesterol, and serum
      triacylglycerol. Levels of serum biochemical factors, calcium, phosphorus, and
      glucose were also insignificantly altered by collagen hydrolysate
      supplementation. Conclusion: Collagen hydrolysate supplementation reduced body
      weight gain and adipocyte enlargement in response to ovariectomy but slightly
      affected blood lipids, calcium, and glucose in both sham-operated and OVX rats.
      Collagen hydrolysate supplementation is beneficial in ameliorating estrogen
      deficiency-induced obesity and its associated risk factors.

PMID- 27877078
TI  - Activation of the CXCL16/CXCR6 Pathway by Inflammation Contributes to
      Atherosclerosis in Patients with End-stage Renal Disease.
AB  - Background: Chronic inflammation plays a critical role in the progression of
      atherosclerosis (AS). This study aimed to determine the effects of the CXC
      chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway on
      cholesterol accumulation in the radial arteries of end-stage renal disease (ESRD)
      patients with concomitant microinflammation and to further investigate the
      potential effects of the purinergic receptor P2X ligand-gated ion channel 7
      (P2X7R). Methods: Forty-three ESRD patients were divided into the control group
      (n=17) and the inflamed group (n=26) based on plasma C-reactive protein (CRP)
      levels. Biochemical indexes and lipid profiles of the patients were determined.
      Surgically removed tissues from the radial arteries of patients receiving
      arteriovenostomy were used for preliminary evaluation of AS. Haematoxylin-eosin
      (HE) and Filipin staining were performed to assess foam cell formation.
      CXCL16/CXCR6 pathway-related protein expression, P2X7R protein expression and the
      expression of monocyte chemotactic protein-1 (MCP-1), tumour necrosis factor
      alpha (TNF-alpha), and CD68 were detected by immunohistochemical and
      immunofluorescence staining. Results: Inflammation increased both MCP-1 and TNF
      alpha expression and macrophage infiltration in radial arteries. Additionally,
      foam cell formation significantly increased in the radial arteries of the
      inflamed group compared to that of the controls. Further analysis showed that
      protein expression of CXCL16, CXCR6, disintegrin and metalloproteinase-10
      (ADAM10) in the radial arteries of the inflamed group was significantly
      increased. Furthermore, CXCL16 expression was positively correlated with P2X7R
      expression in the radial arteries of ESRD patients. Conclusions: Inflammation
      contributed to foam cell formation in the radial arteries of ESRD patients via
      activation of the CXCL16/CXCR6 pathway, which may be regulated by P2X7R.

PMID- 27877079
TI  - Amplification and overexpression of CTTN and CCND1 at chromosome 11q13 in
      Esophagus squamous cell carcinoma (ESCC) of North Eastern Chinese Population.
AB  - Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and
      is a major cause of cancer-related mortality. The combination of genetics, diet,
      behavior, and environment plays an important role in the carcinogenesis of ESCC.
      To characterize the genomic aberrations of this disease, we investigated the
      genomic imbalances in 19 primary ESCC cases using high-resolution array
      comparative genomic hybridization (CGH). All cases showed either loss or gain of
      whole chromosomes or segments of chromosome(s) with variable genomic sizes. The
      copy number alterations per case affected the median 34% (~ 1,034Mb/3,000Mb) of
      the whole genome. Recurrent gains were 1q21.3-qter, 3q13.11-qter, 5pter-p11,
      7pter-p15.3, 7p12.1-p11.2, 7q11-q11.2, 8p12-qter, 11q13.2-q13.3, 12pter-p13.31,
      17q24.2, 20q11.21-qter, and 22q11.21-q11.22 whereas the recurrent losses were
      3pter-p11.1, 4pter-p12, 4q28.3-q31.22, 4q31.3-q32.1, 9pter-p12, 11q22.3-qter and
      13q12.11-q22.1. Amplification of 11q13 resulting in overexpression of CTTN/CCND1
      was the most prominent finding, which was observed in 13 of 19 ESCC cases. These
      unique profiles of copy number alteration should be validated by further studies
      and need to be taken into consideration when developing biomarkers for early
      detection of ESCC.

PMID- 27877080
TI  - Established Population of Blacklegged Ticks with High Infection Prevalence for
      the Lyme Disease Bacterium, Borrelia burgdorferi Sensu Lato, on Corkscrew Island,
      Kenora District, Ontario.
AB  - We document an established population of blacklegged ticks, Ixodes scapularis, on
      Corkscrew Island, Kenora District, Ontario, Canada. Primers of the outer surface
      protein A (OspA) gene, the flagellin (fla) gene, and the flagellin B (flaB) gene
      were used in the PCR assays to detect Borrelia burgdorferi sensu lato (s.l.), the
      Lyme disease bacterium. In all, 60 (73%) of 82 adult I. scapularis, were infected
      with B. burgdorferi s.l. As well, 6 (43%) of 14 unfed I. scapularis nymphs were
      positive for B. burgdorferi s.l. An I. scapularis larva was also collected from a
      deer mouse, and several unfed larvae were gathered by flagging leaf litter. Based
      on DNA sequencing of randomly selected Borrelia amplicons from six nymphal and
      adult I. scapularis ticks, primers for the flagellin (fla) and flagellin B (flaB)
      genes reveal the presence of B. burgdorferi sensu stricto (s.s.), a genospecies
      pathogenic to humans and certain domestic animals. We collected all 3 host
      feeding life stages of I. scapularis in a single year, and report the
      northernmost established population of I. scapularis in Ontario. Corkscrew Island
      is hyperendemic for Lyme disease and has the highest prevalence of B. burgdorferi
      s.l. for any established population in Canada. Because of this very high
      infection prevalence, this population of I. scapularis has likely been
      established for decades. Of epidemiological significance, cottage owners, island
      visitors, outdoors enthusiasts, and medical professionals must be vigilant that
      B. burgdorferi s.l.-infected I. scapularis on Corkscrew Island pose a serious
      public health risk.

PMID- 27877081
TI  - P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice
      by increasing tissue stiffness.
AB  - P-selectin, a cell adhesion molecule, is an important member of the selectin
      family. Recent studies have shown that P-selectin deletion inhibits tumor growth
      in Rip1-Tag2 mice by suppressing platelet accumulation in tumor tissues. This
      study aimed to evaluate whether and how P-selectin affects tumor stiffness in
      Rip1-Tag2 mice. To explore the role of P-selectin in tissue stiffness, we
      demonstrated that tumor progression in Rip1-Tag2 mice was correlated with tissue
      stiffness using immunofluorescence and histological staining. Furthermore, we
      showed that P-selectin deficiency significantly decreased tissue stiffness by
      inhibiting lysyl oxidase (LOX) expression. Our experiments involving Rip1-Tag2
      mice treated with the LOX inhibitor BAPN showed that BAPN significantly abolished
      collagen deposition to decrease tumor stiffness and thus inhibit tumor growth.
      These results indicate that P-selectin deletion significantly decreases tumor
      stiffness in Rip1-Tag2 mice by inhibiting LOX expression. Further study
      demonstrated that P-selectin-mediated platelet accumulation increases tissue
      stiffness mainly by increasing LOX expression and thus promotes tumor growth.
      Therefore, P-selectin may be an effective therapeutic targeting for treating
      human insulinomas.

PMID- 27877082
TI  - Histone Deacetylase Inhibitor Trichostatin a Promotes the Apoptosis of
      Osteosarcoma Cells through p53 Signaling Pathway Activation.
AB  - Purpose: The purpose of this study was to investigate the profile of histone
      deacetylase (HDAC) activity and expression in osteosarcoma cells and tissues from
      osteosarcoma patients and to examine the mechanism by which a histone deacetylase
      (HDAC) inhibitor, Trichostatin A (TSA), promotes the apoptosis of osteosarcoma
      cells. Methods: HDAC activity and histone acetyltransferase (HAT) activity were
      determined in nuclear extracts of MG63 cells, hFOB 1.19 cells and tissues from 6
      patients with primary osteosarcoma. The protein expression of Class I HDACs (1,
      2, 3 and 8) and the activation of the p53 signaling pathway were examined by
      Western blot. Cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2
      thiazolyl)-2H-tetrazolium bromide (MTT) assay and flow cytometry, respectively.
      Results: Nuclear HDAC activity and class I HDAC expression were significantly
      higher in MG63 cells than in hFOB 1.19 cells, and a similar trend was observed in
      the human osteosarcoma tissues compared with the paired adjacent non-cancerous
      tissues. TSA significantly inhibited the growth of MG63 cells and promoted
      apoptosis in a dose-dependent manner through p53 signaling pathway activation.
      Conclusion: Class I HDACs play a central role in the pathogenesis of
      osteosarcoma, and HDAC inhibitors may thus have promise as new therapeutic agents
      against osteosarcoma.

PMID- 27877084
TI  - RNA interference of chitin synthase genes inhibits chitin biosynthesis and
      affects larval performance in Leptinotarsa decemlineata (Say).
AB  - Dietary introduction of bacterially expressed double-stranded RNA (dsRNA) has
      great potential for management of Leptinotarsa decemlineata. Identification of
      the most attractive candidate genes for RNA interference (RNAi) is the first
      step. In the present paper, three complete chitin synthase cDNA sequences
      (LdChSAa, LdChSAb and LdChSB) were cloned. LdChSAa and LdChSAb, two splicing
      variants of LdChSA gene, were highly expressed in ectodermally-derived epidermal
      cells forming epidermis, trachea, foregut and hindgut, whereas LdChSB was mainly
      transcribed in midgut cells. Feeding bacterially expressed dsChSA (derived from a
      common fragment of LdChSAa and LdChSAb), dsChSAa, dsChSAb and dsChSB in the
      second- and fourth-instar larvae specifically knocked down their target mRNAs.
      RNAi of LdChSAa+LdChSAb and LdChSAa lowered chitin contents in whole body and
      integument samples, and thinned tracheal taenidia. The resulting larvae failed to
      ecdyse, pupate, or emerge as adults. Comparably, knockdown of LdChSAb mainly
      affected pupal-adult molting. The LdChSAb RNAi pupae did not completely shed the
      old larval exuviae, which caused failure of adult emergence. In contrast,
      silencing of LdChSB significantly reduced foliage consumption, decreased chitin
      content in midgut sample, damaged midgut peritrophic matrix, and retarded larval
      growth. As a result, the development of the LdChSB RNAi hypomorphs was arrested.
      Our data reveal that these LdChSs are among the effective candidate genes for an
      RNAi-based control strategy against L. decemlineata.

PMID- 27877083
TI  - Epstein-Barr virus lytic reactivation regulation and its pathogenic role in
      carcinogenesis.
AB  - Epstein-Barr virus (EBV) has been associated with several types of human cancers.
      In the host, EBV can establish two alternative modes of life cycle, known as
      latent or lytic and the switch from latency to the lytic cycle is known as EBV
      reactivation. Although EBV in cancer cells is found mostly in latency, a small
      number of lytically-infected cells promote carcinogenesis through the release of
      growth factors and oncogenic cytokines. This review focuses on the mechanisms by
      which EBV reactivation is controlled by cellular and viral factors, and discusses
      how EBV lytic infection contributes to human malignancies.

PMID- 27877085
TI  - The Evolving Functions of Autophagy in Ocular Health: A Double-edged Sword.
AB  - Autophagy plays an adaptive role in cell survival, development, differentiation
      and intracellular homeostasis. Autophagy is recognized as a 'self-cannibalizing'
      process that is active during stresses such as starvation, chemotherapy,
      infection, ageing, and oxygen shortage to protect organisms from various
      irritants and to regenerate materials and energy. However, autophagy can also
      lead to a form of programmed cell death distinct from apoptosis. Components of
      the autophagic pathway are constitutively expressed at a high level in the eye,
      including in the cornea, lens, retina, and orbit. In addition, the activation of
      autophagy is directly linked to the development of eye diseases such as age
      related macular degeneration (ARMD), cataracts, diabetic retinopathy (DR),
      glaucoma, photoreceptor degeneration, ocular tumours, ocular infections and
      thyroid-associated ophthalmopathy (TAO). A high level of autophagy defends
      against external stress; however, excessive autophagy can result in
      deterioration, as observed in ocular diseases such as ARMD and DR. This review
      summarizes recent developments elucidating the relationship between autophagy and
      ocular diseases and the potential roles of autophagy in the pathogenesis and
      treatment of these diseases.

PMID- 27877086
TI  - Ginsenoside Rg1 Protects against Oxidative Stress-induced Neuronal Apoptosis
      through Myosin IIA-actin Related Cytoskeletal Reorganization.
AB  - Oxidative stress-induced cytoskeletal dysfunction of neurons has been implicated
      as a crucial cause of cell apoptosis or death in the central nervous system (CNS)
      diseases, such as neurodegenerative and psychiatric diseases. The application of
      neuroprotectants rescuing the neurons from cytoskeletal damage and apoptosis can
      be a potential treatment for these CNS diseases. Ginsenoside Rg1 (Rg1), one of
      the major active components of ginseng, has been reported possessing notable
      neuroprotective activities. However, there is rare report about its effect on
      cytoskeleton and its undergoing mechanism. The current study is to reveal the
      regulatory effects of Rg1 on cytoskeletal and morphological lesion in oxidative
      stress-induced neuronal apoptosis. The results demonstrated that pre-treatment
      with Rg1 (0.1-10 MUM) attenuated hydrogen peroxide (H2O2)-induced neuronal
      apoptosis and oxidative stress through reducing the intracellular reactive oxygen
      species (ROS) production and methane dicarboxylic aldehyde (MDA) level. The Rg1
      treatment also abolished H2O2-induced morphological changes, including cell
      rounding, membrane blebbing, neurite retraction and nuclei condensation, which
      were generated by myosin IIA-actin interaction. These effects were mediated via
      the down-regulation of caspase-3, ROCK1 (Rho-associated kinase1) activation and
      myosin light chain (MLC, Ser-19) phosphorylation. Furthermore, inhibiting myosin
      II activity with blebbistatin partly blocked the neuroprotective effects of Rg1.
      The computer-aided homology modelling revealed that Rg1 preferentially positioned
      in the actin binding cleft of myosin IIA and might block the binding of myosin
      IIA to actin filaments. Accordingly, the neuroprotective mechanism of Rg1 is
      related to the activity that inhibits myosin IIA-actin interaction and the
      caspase-3/ROCK1/MLC signaling pathway. These findings put some insights into the
      unique neuroprotective properties of Rg1 associated with the regulation of myosin
      IIA-actin cytoskeletal structure under oxidative stress and provide experimental
      evidence for Rg1 in CNS diseases.

PMID- 27877087
TI  - IL28B SNP rs12979860 is the Critical Predictor for Sustained Viral Response in
      Chinese Children Aged 1 to 6 Years with Chronic Hepatitis C.
AB  - Clinical data on children with chronic hepatitis C (CHC) remain extremely
      limited. This study investigated sustained virologic response (SVR) to alfa
      interferon 2b plus RBV treatment in children aged 1-6 years with unsafe injection
      acquired CHC. 154 children with CHC aged 1 to 6 years were enrolled, 101 of them
      were male (65.6%) and 53 were female (34.4%), and they were treated with alfa
      interferon at a dose of 1-5 MIU/m2 3 times weekly plus oral RBV (15 mg/kg/day)
      for 48 weeks. 57(39.3 %) of them were genotype 1b, 73(50.3%) were genotypes 2a,
      15(10.3%) were undecided type. SVR was achieved in 53 of 57(93.0%) patients with
      genotype 1b, in 72 (98.6%) of 73 with genotype 2a, 15(100.0%) of 15 with
      undecided type. There was no significant statistical difference in SVR between
      male and female (98.0% vs 94.3%, p=0.340), genotype 2a and those with genotype
      1b(98.6% vs 93.0%, p=0.160), ALT>40U/L group and ALT<=40U/L group(96.7% vs 96.8%,
      p=1.000), AST>40U/L group and AST<=40U/L group(95.9% vs 98.2%, p=0.654) as well
      as lower baseline viral load group (<6*105 IU/ml) and higher baseline viral load
      group(>=6*105 IU/ml)(97.3% vs 95.3%, p=0.916). Leucopenia, neutropenia,
      hemoglobin concentration decrease, fever, platelet count decrease and rash were
      8.4%, 69.5%, 24.0%, 50.6%, 1.9% and 4.5%, respectively. And only 12(7.8%)
      individuals developed thyroid autoantibodies. The SVR was higher in patients with
      IL-28B genotype C/C than C/T (99.0% vs 80%, p=0.002). Compared with HCV viral
      genotype, ALT level and baseline viral load, IL-28B rs12979860 is more suitable
      for predicting antiviral efficacy in children with CHC. It is inappropriate to
      take the increase of ALT level as an essential indicator for antiviral treatment
      in children aged 1-6 years.

PMID- 27877088
TI  - Aloe-emodin suppresses hypoxia-induced retinal angiogenesis via inhibition of HIF
      1alpha/VEGF pathway.
AB  - Background: Aloe-emodin (AE) has been reported to possess the antiangiogenic
      effect on laser induced choroidal neovascularization. AE inhibits the vessel
      formation in the zebrafish embryos. However, it is still unclear whether AE can
      alleviate neovascularization. Here, we investigated the inhibitory effect of AE
      on the hypoxia-induced retinal neovascularization and the possible mechanisms.
      Methods: We established a vascular endothelial growth factor (VEGF) secretion
      model under chemical induced hypoxia by exposure of 150 uM CoCl2 to the ARPE-19
      cells, then treated the cells with different concentrations of AE (0.2, 1.0 and
      5.0 ug/mL) or a special hypoxia-inducible factor 1alpha (HIF-1alpha) inhibitor [3
      (5'-hydroxymethyl-2'-furyl)-1-benzylindazole, YC-1, 1.0 ug/mL]. The cellular
      supernatants were collected 48 h later to measure the VEGFA concentrations by
      human VEGFA enzyme-linked immunosorbent assay (ELISA) kits, the mRNA expressions
      of VEGFA, HIF-1alpha and prolyl hydroxylase-2 (PHD-2) by quantitative reverse
      transcription-PCR (qRT-PCR) and the protein expressions of HIF-1alpha and PHD-2
      by Western blots. For in vivo study, the rat pups with oxygen-induced retinopathy
      were treated with Conbercept ophthalmic injection (1.0 mg/kg) or AE (5.0 and 10.0
      mg/kg) for five days, then the retinal avascular areas were assessed via
      visualization of the retinal vasculature with ADPase and hematoxylin & eosin
      (H&E) stains. Results: AE inhibits the VEGFA secretion of ARPE-19 cells under
      hypoxia condition, decreases the mRNA expressions of VEGFA and PHD-2 and the
      protein expressions of VEGFA, HIF-1alpha and PHD-2 in vitro and prevents hypoxia
      induced retinal neovascularization in vivo.Conclusions: AE ameliorates retinal
      neovascularization throuth inhibition of the HIF-1alpha/VEGF signaling pathway.
      AE may be developed as a potential drug for the prevention and treatment of
      diabetic retinopathy.

PMID- 27877089
TI  - Insights into the Nanog gene: A propeller for stemness in primitive stem cells.
AB  - Self-renewal and pluripotency are two major characteristics of embryonic stem
      cells (ESCs) that allow ESCs to maintain stem cell population, and differentiate
      into multiple types of adult tissues. Nanog is the key transcription factor that
      controls both self-renewal and pluripotency of ESCs. Similarly, cancer stem cells
      (CSCs) are capable of preserving population and initiating new tumor development
      by self-renewal. Expression of Nanog family proteins can be increased in many
      types of cancer which is correlated with tumor outcomes. In this review we
      summarized the recent understanding of the roles and mechanisms of Nanog in ESC
      regulation under physiological conditions. In addition, we describe the function
      of Nanog family proteins in different types of cancer, and the association of
      Nanog with clinical outcomes. Taken together, Nanog proteins are central
      regulators controlling both ESCs and CSCs, and are considered as a prognostic
      marker in many types of cancer. These findings supported the possibility of novel
      therapeutic potentials of Nanog against cancers.

PMID- 27877090
TI  - Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in
      Laying Hens in a Diet-Specific Manner.
AB  - Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs
      trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex
      genetic and dietary regulation, closely linked to cardiovascular disease risk. We
      determined whether the genetic defects in TMA metabolism may change other
      metabolic traits in birds, determined whether the genetic effects depend on
      diets, and to identify genes or gene pathways that underlie the metabolic
      alteration induced by genetic and diet factors. We used hens genotyped as FMO3
      c.984 A>T as well as those with the homozygous normal genotype. For each
      genotype, hens were provided with either a corn-soybean meal basal diets (SM),
      which contains lower levels of TMA precursor, or the basal diets supplemented
      with 21% of rapeseed meal (RM), which contains higher levels of TMA precursor. An
      integrative analysis of metabolomic and transcriptomic was used to explore the
      metabolic patterns of FMO3 genetic variant in hens that were fed the two defined
      diets. In birds that consumed SM diets, the T329S mutation increased levels of
      plasma TMA and lipids, FMO3 mRNA levels, and the expression of genes involved in
      long chain polyunsaturated fatty acid biosynthesis. In birds that consumed RM
      diets, the T329S mutation induced fishy odor syndrome, a repression in LXR
      pathway and a reciprocal change in lipid metabolism. Variations in TMA and lipid
      metabolism were linked to the genetic variant in FMO3 in a diet-specific manner,
      which suggest FMO3 functions in TMA metabolism and lipid homeostasis. LXR pathway
      and polyunsaturated fatty acid metabolism are two possible mechanisms of FMO3
      action in response to dietary TMA precursor.

PMID- 27877091
TI  - Conserved chemosensory proteins in the proboscis and eyes of Lepidoptera.
AB  - Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are endowed with
      several different functions besides being carriers for pheromones and odorants.
      Based on a previous report of a CSP acting as surfactant in the proboscis of the
      moth Helicoverpa armigera, we revealed the presence of orthologue proteins in two
      other moths Plutella xylostella and Chilo suppressalis, as well as two
      butterflies Papilio machaon and Pieris rapae, using immunodetection and proteomic
      analysis. The unusual conservation of these proteins across large phylogenetic
      distances indicated a common specific function for these CSPs. This fact prompted
      us to search for other functions of these proteins and discovered that CSPs are
      abundantly expressed in the eyes of H. armigera and possibly involved as carriers
      for carotenoids and visual pigments. This hypothesis is supported by ligand
      binding experiments and docking simulations with retinol and beta-carotene. This
      last orange pigment, occurring in many fruits and vegetables, is an antioxidant
      and the precursor of visual pigments. We propose that structurally related CSPs
      solubilise nutritionally important carotenoids in the proboscis, while they act
      as carriers of both beta-carotene and its derived products 3-hydroxyretinol and 3
      hydroxyretinal in the eye. The use of soluble olfactory proteins, such as CSPs,
      as carriers for visual pigments in insects, here reported for the first time,
      parallels the function of retinol-binding protein in vertebrates, a lipocalin
      structurally related to vertebrate odorant-binding proteins.

PMID- 27877093
TI  - Adolescent Clinical Development of Ezogabine/Retigabine as Adjunctive Therapy for
      Partial-Onset Seizures: Pharmacokinetics and Tolerability.
AB  - OBJECTIVES: To explore the pharmacokinetic (PK) profile and safety of ezogabine
      (EZG)/retigabine (RTG) as adjunctive therapy for uncontrolled partial-onset
      seizures (POS) in adolescents. METHODS: In this multiple-dose study
      (NCT01494584), adolescents with POS received EZG/RTG immediate-release tablets
      three times daily (TID) as adjunctive therapy to 1 to 3 concurrent antiepileptic
      drugs. The study comprised a screening phase, and a 5- to 8-week treatment phase
      starting with 100 mg TID up-titrated once weekly by <=50 mg TID to a maximum
      dosage of 300 mg TID. There were 8 venous blood samples and 2 finger-prick blood
      samples collected for PK analysis during 8-hour time periods at the target
      dosages of 100, 200, and 300 mg TID. RESULTS: This study was terminated
      prematurely on US Food and Drug Administration advice due to
      pigmentation/discoloration findings in long-term, open-label extension studies in
      adults. Five participants (ages 13-16 years) had enrolled in the study. For the
      EZG/RTG 100-, 200-, and 300-mg doses, the area under the concentration-time curve
      during the dosage intervals was 1680, 2559, and 3784 ng/hr/mL; maximum plasma
      concentrations were 370, 536, and 751 ng/mL, and minimum plasma concentrations
      were 105, 200, and 287 ng/mL, respectively. Venous and finger-prick
      concentrations of EZG/RTG were similar. No significant adverse events were
      observed during treatment (133-213 days). CONCLUSIONS: EZG/RTG PK appeared linear
      across the dosage range of 100 to 300 mg TID in adolescents with POS, and were
      consistent with adult observations. The small sample size and short study
      duration preclude conclusions regarding the safety and efficacy of EZG/RTG.

PMID- 27877094
TI  - Raman Spectroscopy: A Sensitive and Specific Technique for Determining the
      Accuracy of Compounded Pharmaceutical Formulations.
AB  - OBJECTIVES: Raman spectroscopy is a widely used technology to identify chemical
      unknowns or confirm chemical identity. We have tested Raman spectrometry to
      identify compounded pharmaceutical formulations. In contrast to the commonly used
      application mentioned above, compounded pharmaceutical formulations contain a
      mixture of ingredients, and the Raman spectrometer is being used to correctly
      identify the composition of the complete pharmaceutical formulation, including
      the active pharmaceutical ingredient(s). The objective of this pilot study was to
      document the potential use of Raman spectroscopy as a tool to provide quality
      control to compounded pharmaceutical formulations. METHODS: "Testing a test"
      study design was used to prospectively determine whether Raman spectroscopy could
      verify the accuracy of compounded pharmaceutical formulations. A total of 9
      formulations that are commonly compounded at Cook Children's Health Center were
      selected for testing. Each of the 9 formulations and 2 blank controls were
      randomly tested for compounding accuracy in replicate. A total of 110 tests were
      conducted. RESULTS: Raman spectroscopy was found to be a reliable test to
      determine the accuracy of compounded pharmaceutical formulations with a 100%
      positive predictive value. CONCLUSIONS: Raman spectroscopy promises to be an
      excellent tool for compounding pharmacies to provide an objective measure of
      compounding accuracy to their unique, compounded pharmaceutical formulations.

PMID- 27877095
TI  - Evaluation of the Tolerability of Intermittent Intravenous Sildenafil in
      Pediatric Patients With Pulmonary Hypertension.
AB  - OBJECTIVES: The primary purpose of this study was to determine the tolerability
      of intermittent intravenous (IV) sildenafil for the treatment of pulmonary
      hypertension in pediatric patients. Secondary objectives were to evaluate
      parameters related to efficacy. METHODS: This was a retrospective chart review
      from January 2013 to August 2014 of pediatric patients under age 18 years treated
      with intermittent doses of IV sildenafil for pulmonary hypertension. Patients
      were excluded if they were over age 18 years or received sildenafil for other
      indications. Measures collected to assess tolerability include blood pressure and
      heart rate before and after the administration of IV sildenafil, as well as
      adverse events. RESULTS: Thirty-seven patients (21 females and 16 males) were
      identified meeting inclusion criteria, and 21 (56.8%) were on oral sildenafil
      prior to the initial IV dose. The mean decrease in blood pressure after the first
      dose of IV sildenafil was 7.16/2.74 mmHg. The decrease in systolic blood pressure
      was statistically significant. During the study period, 5 patients experienced
      medication related adverse events, primarily hypotension. Despite this, none of
      the patients had the medication discontinued due to these events. For secondary
      objectives, a statistically significant difference was not found between other
      clinical measures before and after intermittent IV sildenafil dosing.
      CONCLUSIONS: Sildenafil, when administered as intermittent IV doses, was
      tolerated by the majority of patients evaluated in this study. For pediatric
      patients with pulmonary hypertension in whom enteral or continuous IV sildenafil
      cannot be administered, intermittent IV sildenafil may be considered as an
      alternative administration option.

PMID- 27877096
TI  - A Prospective Pilot Study on the Systemic Absorption of Oral Vancomycin in
      Children With Colitis.
AB  - BACKGROUND: Oral vancomycin is used to treat refractory colitis due to
      Clostridium dificile infection. Traditionally, oral vancomycin was thought to not
      be absorbed systemically, but recent adult studies have demonstrated detectable
      serum levels in over half of patients with severe colitis. This has not been
      studied in children. OBJECTIVE: To determine the absorption of oral vancomycin
      and the renal safety profile of oral vancomycin in children hospitalized with
      colitis. METHODS: We performed a prospective, observational, pilot proof of
      principle study at the North Carolina Children's Hospital in patients 2 years to
      18 years of age receiving oral vancomycin for the treatment of C dificile
      colitis. Severity of disease was determined using a validated scoring system.
      Serial serum vancomycin levels and renal function tests were performed during the
      administration of oral vancomycin. RESULTS: All patients enrolled (n = 8) had
      mild to moderate C dificile colitis and varying severity of underlying systemic
      diseases; 7 with inflammatory bowel disease and 1 with acute kidney injury
      following renal transplantation. No enrolled patients had detectable levels of
      serum vancomycin. Additionally, no adverse renal outcomes were attributed to oral
      vancomycin, and no cases of "Red Man" syndrome were observed. CONCLUSIONS: Unlike
      studies in adult patients, oral vancomycin is likely not absorbed in children
      with mild to moderate colitis. Further study is needed to determine the
      pharmacokinetics in severe colitis and those with severe illness in a critical
      care setting.

PMID- 27877097
TI  - Preoperative Antibiotic Orders: Protocol-Initiated Pharmacist Order Entry.
AB  - OBJECTIVE: To evaluate the antibiotic selection of preoperative orders before and
      after a pharmacist order entry protocol for patients with methicillin-resistant
      Staphylococcus aureus (MRSA) colonization. METHODS: A retrospective chart review
      of orthopedic surgery procedures on patients with MRSA colonization at a free
      standing, academic pediatric hospital, between February 2010 and February 2012.
      RESULTS: Procedures that were performed pre protocol (n = 27) implementation had
      a 63% rate of appropriate antibiotic selection compared to 81% in the
      postprotocol group (n = 32; p = 0.1155). The preprotocol group dose accuracy was
      96% compared to 97% in the postprotocol group (p = 0.81). Two procedures, 1 in
      each group, were redosed appropriately for extended surgery duration. Correct
      timing of antibiotic administration occurred in 82% of cases pre protocol versus
      68% post protocol (p = 0.42). CONCLUSIONS: Patients with MRSA colonization had a
      greater rate of appropriate drug selection after the implementation of a
      pharmacist-initiated preoperative protocol. Correct antibiotic dose and redose
      remained consistent between the study groups. Most of the orthopedic procedures
      performed included patients on antibiotic coverage at steady state for ongoing
      infections, which impacted the analysis of preoperative timing. Further studies
      should be conducted to assess whether the increase in the number of appropriate
      antibiotic selections decreases the rate of postoperative MRSA infections.

PMID- 27877098
TI  - Accidental Epidural Injection of Rocuronium in a Pediatric Patient: A Case Report
      and Literature Review.
AB  - Accidental administration of non-epidural drugs into the epidural or subarachnoid
      spaces may be associated with unexpected pain, morbidity, adverse effects,
      increased level of care, prolonged hospital stay, and mortality. We describe a 12
      month-old admitted for secondary-stage hypospadias reconstruction. General
      anesthesia was induced with sevofiurane and a peripheral catheter was placed.
      Instead of ropivacaine, rocuronium (80 mg; 6.3 mg/kg) was injected into the
      epidural space by the caudal route. Surgery was uneventful and was completed 160
      minutes after rocuronium was given. The patient exhibited paralysis with 1 of 4
      twitches to the train-of-four with some posttetanic potentiation at the end of
      surgery. He was transferred to the pediatric intensive care unit for supportive
      ventilation and recovery. He did not experience oxygen desaturation or
      hypoventilation between the time of rocuronium administration and intubation. He
      was hemodynamically stable, without respiratory insufficiency, and his neurologic
      exam was normal, without motor or sensorial block. The patient was discharged
      home on the morning of the first postoperative day. Clinical examination 1 week
      after surgery revealed no lasting sequelae from the error.

PMID- 27877099
TI  - Asthma Review for Pharmacists Providing Asthma Education.
AB  - Asthma is the most common pediatric illness affecting more than 6 million
      children in the United States. Children with asthma have more frequent office
      visits and hospitalizations compared with adults. Despite advances in therapies,
      asthma still has a significant effect on the health care system. Regardless of
      the setting, pharmacists are uniquely equipped with an intimate knowledge of
      medications. With this knowledge, they can provide education to patients at
      various points throughout the health care system, from hospitalization to office
      visits to point of pick up at the pharmacy. The goal of this article is to equip
      the pharmacist with the necessary knowledge to provide education to these
      patients in a variety of practice settings, including community pharmacies,
      ambulatory care settings, and during transitions in care.

PMID- 27877092
TI  - Pediatric Statin Administration: Navigating a Frontier with Limited Data.
AB  - Increasingly, children and adolescents with dyslipidemia qualify for
      pharmacologic intervention. As they are for adults, 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase inhibitors (statins) are the mainstay of pediatric
      dyslipidemia treatment when lifestyle modifications have failed. Despite the
      overall success of these drugs, the magnitude of variability in dose-exposure
      response profiles contributes to adverse events and treatment failure. In
      children, the cause of treatment failures remains unclear. This review describes
      the updated guidelines for screening and management of pediatric dyslipidemia and
      statin disposition pathway to assist the provider in recognizing scenarios where
      alterations in dosage may be warranted to meet patients' specific needs.

PMID- 27877100
TI  - Striatal and Tegmental Neurons Code Critical Signals for Temporal-Difference
      Learning of State Value in Domestic Chicks.
AB  - To ensure survival, animals must update the internal representations of their
      environment in a trial-and-error fashion. Psychological studies of associative
      learning and neurophysiological analyses of dopaminergic neurons have suggested
      that this updating process involves the temporal-difference (TD) method in the
      basal ganglia network. However, the way in which the component variables of the
      TD method are implemented at the neuronal level is unclear. To investigate the
      underlying neural mechanisms, we trained domestic chicks to associate color cues
      with food rewards. We recorded neuronal activities from the medial striatum or
      tegmentum in a freely behaving condition and examined how reward omission changed
      neuronal firing. To compare neuronal activities with the signals assumed in the
      TD method, we simulated the behavioral task in the form of a finite sequence
      composed of discrete steps of time. The three signals assumed in the simulated
      task were the prediction signal, the target signal for updating, and the TD-error
      signal. In both the medial striatum and tegmentum, the majority of recorded
      neurons were categorized into three types according to their fitness for three
      models, though these neurons tended to form a continuum spectrum without distinct
      differences in the firing rate. Specifically, two types of striatal neurons
      successfully mimicked the target signal and the prediction signal. A linear
      summation of these two types of striatum neurons was a good fit for the activity
      of one type of tegmental neurons mimicking the TD-error signal. The present study
      thus demonstrates that the striatum and tegmentum can convey the signals
      critically required for the TD method. Based on the theoretical and
      neurophysiological studies, together with tract-tracing data, we propose a novel
      model to explain how the convergence of signals represented in the striatum could
      lead to the computation of TD error in tegmental dopaminergic neurons.

PMID- 27877102
TI  - Inhibition of GABAergic Neurotransmission by HIV-1 Tat and Opioid Treatment in
      the Striatum Involves MU-Opioid Receptors.
AB  - Due to combined antiretroviral therapy (cART), human immunodeficiency virus type
      1 (HIV-1) is considered a chronic disease with high prevalence of mild forms of
      neurocognitive impairments, also referred to as HIV-associated neurocognitive
      disorders (HAND). Although opiate drug use can exacerbate HIV-1 Tat-induced
      neuronal damage, it remains unknown how and to what extent opioids interact with
      Tat on the GABAergic system. We conducted whole-cell recordings in mouse striatal
      slices and examined the effects of HIV-1 Tat in the presence and absence of
      morphine (1 MUM) and damgo (1 MUM) on GABAergic neurotransmission. Results
      indicated a decrease in the frequency and amplitude of spontaneous inhibitory
      postsynaptic currents (sIPSCs) and miniature IPSCs (mIPSCs) by Tat (5-50 nM) in a
      concentration-dependent manner. The significant Tat-induced decrease in IPSCs was
      abolished when removing extracellular and/or intracellular calcium. Treatment
      with morphine or damgo alone significantly decreased the frequency, but not
      amplitude of IPSCs. Interestingly, morphine but not damgo indicated an additional
      downregulation of the mean frequency of mIPSCs in combination with Tat.
      Pretreatment with naloxone (1 MUM) and CTAP (1 MUM) prevented the Tat-induced
      decrease in sIPSCs frequency but only naloxone prevented the combined Tat and
      morphine effect on mIPSCs frequency. Results indicate a Tat- or opioid-induced
      decrease in GABAergic neurotransmission via MU-opioid receptors with combined Tat
      and morphine effects involving additional opioid receptor-related mechanisms.
      Exploring the interactions between Tat and opioids on the GABAergic system may
      help to guide future research on HAND in the context of opiate drug use.

PMID- 27877103
TI  - Neural Underpinnings of Decision Strategy Selection: A Review and a Theoretical
      Model.
AB  - In multi-attribute choice, decision makers use decision strategies to arrive at
      the final choice. What are the neural mechanisms underlying decision strategy
      selection? The first goal of this paper is to provide a literature review on the
      neural underpinnings and cognitive models of decision strategy selection and thus
      set the stage for a neurocognitive model of this process. The second goal is to
      outline such a unifying, mechanistic model that can explain the impact of
      noncognitive factors (e.g., affect, stress) on strategy selection. To this end,
      we review the evidence for the factors influencing strategy selection, the neural
      basis of strategy use and the cognitive models of this process. We also present
      the Bottom-Up Model of Strategy Selection (BUMSS). The model assumes that the use
      of the rational Weighted Additive strategy and the boundedly rational heuristic
      Take The Best can be explained by one unifying, neurophysiologically plausible
      mechanism, based on the interaction of the frontoparietal network, orbitofrontal
      cortex, anterior cingulate cortex and the brainstem nucleus locus coeruleus.
      According to BUMSS, there are three processes that form the bottom-up mechanism
      of decision strategy selection and lead to the final choice: (1) cue weight
      computation, (2) gain modulation, and (3) weighted additive evaluation of
      alternatives. We discuss how these processes might be implemented in the brain,
      and how this knowledge allows us to formulate novel predictions linking strategy
      use and neural signals.

PMID- 27877104
TI  - Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in
      the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness.
AB  - The hypothalamic feeding center plays an important role in energy homeostasis. In
      the feeding center, whole-body energy signals including hormones and nutrients
      are sensed, processed, and integrated. As a result, food intake and energy
      expenditure are regulated. Two types of glucose-sensing neurons exist in the
      hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited
      neurons. While some molecules are known to be related to glucose sensing in the
      hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are
      not fully understood. The sweet taste receptor is a heterodimer of taste type 1
      receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes.
      T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas,
      adipose tissue, and hypothalamus. However, the role of sweet taste receptors in
      the ARC remains to be clarified. To examine the role of sweet taste receptors in
      the ARC, cytosolic Ca2+ concentration ([Ca2+]i) in isolated single ARC neurons
      were measured using Fura-2 fluorescent imaging. An artificial sweetener,
      sucralose at 10-5-10-2 M dose dependently increased [Ca2+]i in 12-16% of ARC
      neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste
      receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was
      inhibited under an extracellular Ca2+-free condition and in the presence of an L
      type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were
      activated by high-concentration of glucose. This response to glucose was markedly
      suppressed by gurmarin. More than half of sucralose-responding neurons were
      activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC)
      neurons among sucralose-responding neurons and sweet taste receptor expressing
      neurons were low, suggesting that majority of sucralose-responding neurons are
      non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular
      activation mainly occurs on non-POMC leptin-responding neurons and contributes to
      glucose responding. Endogenous sweet molecules including glucose may regulate
      energy homeostasis through sweet taste receptors on glucose-and leptin-responsive
      neurons in the ARC.

PMID- 27877101
TI  - From Molecules to the Clinic: Linking Schizophrenia and Metabolic Syndrome
      through Sphingolipids Metabolism.
AB  - Metabolic syndrome (MS) is a prevalent and severe comorbidity observed in
      schizophrenia (SZ). The exact nature of this association is controversial and
      very often accredited to the effects of psychotropic medications and disease
      induced life-style modifications, such as inactive lifestyle, poor dietary
      choices, and smoking. However, drug therapy and disease-induced lifestyle factors
      are likely not the only factors contributing to the observed converging nature of
      these conditions, since an increased prevalence of MS is also observed in first
      episode and drug-naive psychosis populations. MS and SZ share common intrinsic
      susceptibility factors and etiopathogenic mechanisms, which may change the way we
      approach clinical management of SZ patients. Among the most relevant common
      pathogenic pathways of SZ and MS are alterations in the sphingolipids (SLs)
      metabolism and SLs homeostasis. SLs have important structural functions as they
      participate in the formation of membrane "lipid rafts." SLs also play
      physiological roles in cell differentiation, proliferation, and inflammatory
      processes, which might be part of MS/SZ common pathophysiological processes. In
      this article we review a plausible mechanism to explain the link between MS and
      SZ through a disruption in SL homeostasis. Additionally, we provide insights on
      how this hypothesis can lead to the developing of new diagnostic/therapeutic
      technologies for SZ patients.

PMID- 27877105
TI  - Extended Postnatal Brain Development in the Longest-Lived Rodent: Prolonged
      Maintenance of Neotenous Traits in the Naked Mole-Rat Brain.
AB  - The naked mole-rat (NMR) is the longest-lived rodent with a maximum lifespan >31
      years. Intriguingly, fully-grown naked mole-rats (NMRs) exhibit many traits
      typical of neonatal rodents. However, little is known about NMR growth and
      maturation, and we question whether sustained neotenous features when compared to
      mice, reflect an extended developmental period, commensurate with their
      exceptionally long life. We tracked development from birth to 3 years of age in
      the slowest maturing organ, the brain, by measuring mass, neural stem cell
      proliferation, axonal, and dendritic maturation, synaptogenesis and myelination.
      NMR brain maturation was compared to data from similar sized rodents, mice, and
      to that of long-lived mammals, humans, and non-human primates. We found that at
      birth, NMR brains are significantly more developed than mice, and rather are more
      similar to those of newborn primates, with clearly laminated hippocampi and
      myelinated white matter tracts. Despite this more mature brain at birth than
      mice, postnatal NMR brain maturation occurs at a far slower rate than mice,
      taking four-times longer than required for mice to fully complete brain
      development. At 4 months of age, NMR brains reach 90% of adult size with stable
      neuronal cytostructural protein expression whereas myelin protein expression does
      not plateau until 9 months of age in NMRs, and synaptic protein expression
      continues to change throughout the first 3 years of life. Intriguingly, NMR
      axonal composition is more similar to humans than mice whereby NMRs maintain
      expression of three-repeat (3R) tau even after brain growth is complete; mice
      experience an abrupt downregulation of 3R tau by postnatal day 8 which continues
      to diminish through 6 weeks of age. We have identified key ages in NMR cerebral
      development and suggest that the long-lived NMR may provide neurobiologists an
      exceptional model to study brain developmental processes that are compressed in
      common short-lived laboratory animal models.

PMID- 27877107
TI  - Training Deep Spiking Neural Networks Using Backpropagation.
AB  - Deep spiking neural networks (SNNs) hold the potential for improving the latency
      and energy efficiency of deep neural networks through data-driven event-based
      computation. However, training such networks is difficult due to the non
      differentiable nature of spike events. In this paper, we introduce a novel
      technique, which treats the membrane potentials of spiking neurons as
      differentiable signals, where discontinuities at spike times are considered as
      noise. This enables an error backpropagation mechanism for deep SNNs that follows
      the same principles as in conventional deep networks, but works directly on spike
      signals and membrane potentials. Compared with previous methods relying on
      indirect training and conversion, our technique has the potential to capture the
      statistics of spikes more precisely. We evaluate the proposed framework on
      artificially generated events from the original MNIST handwritten digit
      benchmark, and also on the N-MNIST benchmark recorded with an event-based dynamic
      vision sensor, in which the proposed method reduces the error rate by a factor of
      more than three compared to the best previous SNN, and also achieves a higher
      accuracy than a conventional convolutional neural network (CNN) trained and
      tested on the same data. We demonstrate in the context of the MNIST task that
      thanks to their event-driven operation, deep SNNs (both fully connected and
      convolutional) trained with our method achieve accuracy equivalent with
      conventional neural networks. In the N-MNIST example, equivalent accuracy is
      achieved with about five times fewer computational operations.

PMID- 27877108
TI  - Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with
      Advanced Glycation End Products in Normal and Diabetic Rats.
AB  - Diabetes mellitus (DM) causes important modifications in the availability and use
      of different energy substrates in various organs and tissues. Similarly, dietary
      manipulations such as high fat diets also affect systemic energy metabolism.
      However, how the brain adapts to these situations remains unclear. To investigate
      these issues, control and alloxan-induced type I diabetic rats were fed either a
      standard or a high fat diet enriched with advanced glycation end products (AGEs)
      (HAGE diet). The HAGE diet increased their levels of blood ketone bodies, and
      this effect was exacerbated by DM induction. To determine the effects of diet
      and/or DM induction on key cerebral bioenergetic parameters, both ketone bodies
      (beta-hydroxybutyric acid) and lactate oxidation were measured. In parallel, the
      expression of Monocarboxylate Transporter 1 (MCT1) and 2 (MCT2) isoforms in
      hippocampal and cortical slices from rats submitted to these diets was assessed.
      Ketone body oxidation increased while lactate oxidation decreased in hippocampal
      and cortical slices in both control and diabetic rats fed a HAGE diet. In
      parallel, the expression of both MCT1 and MCT2 increased only in the cerebral
      cortex in diabetic rats fed a HAGE diet. These results suggest a shift in the
      preferential cerebral energy substrate utilization in favor of ketone bodies in
      animals fed a HAGE diet, an effect that, in DM animals, is accompanied by the
      enhanced expression of the related transporters.

PMID- 27877109
TI  - NPAS3 Regulates Transcription and Expression of VGF: Implications for
      Neurogenesis and Psychiatric Disorders.
AB  - Neuronal PAS domain protein 3 (NPAS3) and VGF (VGF Nerve Growth Factor (NGF)
      Inducible) are important for neurogenesis and psychiatric disorders. Previously,
      we have demonstrated that NPAS3 regulates VGF at the transcriptional level. In
      this study, VGF (non-acronymic) was found regulated by NPAS3 in neuronal stem
      cells. However, the underlying mechanism of this regulation remains unclear. The
      aim of this study was to explore the correlation of NPAS3 and VGF, and their
      roles in neural cell proliferation, in the context of psychiatric illnesses.
      First, we focused on the structure of NPAS3, to identify the functional domain of
      NPAS3. Truncated NPAS3 lacking transactivation domain was also found to activate
      VGF, which suggested that not only transactivation domain but other structural
      motifs were also involved in the regulation. Second, Mutated enhancer box (E-box)
      of VGF promoter showed a significant response to this basic helix-loop-helix
      (bHLH) transcription factor, which suggested an indirect regulatory mechanism for
      controlling VGF expression by NPAS3. kappaB site within VGF promoter was
      identified for VGF activation induced by NPAS3, apart from direct binding to E
      box. Furthermore, ectopically expressed NPAS3 in PC12 cells produced parallel
      responses for nuclear factor kappa-light-chain-enhancer of activated B cells [NF
      kappaB (P65)] expression, which specifies that NPAS3 regulates VGF through the NF
      kappaB signaling pathway. Over-expression of NPAS3 also enhances the cell
      proliferation, which can be blocked by knockdown of VGF. Finally, NPAS3 was found
      to influence proliferation of neural cells through VGF. Therefore, downstream
      signaling pathways that are responsible for NPAS3-VGF induced proliferation via
      glutamate receptors were explored. Combining this work and published literature,
      a potential network composed by NPAS3, NF-kappaB, Brain-Derived Neurotrophic
      Factor (BDNF), NGF and VGF, was proposed. This network collectively detailed how
      NPAS3 connects with VGF and intersected neural cell proliferation, synaptic
      activity and psychiatric disorders.

PMID- 27877106
TI  - The Language, Tone and Prosody of Emotions: Neural Substrates and Dynamics of
      Spoken-Word Emotion Perception.
AB  - Rapid assessment of emotions is important for detecting and prioritizing salient
      input. Emotions are conveyed in spoken words via verbal and non-verbal channels
      that are mutually informative and unveil in parallel over time, but the neural
      dynamics and interactions of these processes are not well understood. In this
      paper, we review the literature on emotion perception in faces, written words,
      and voices, as a basis for understanding the functional organization of emotion
      perception in spoken words. The characteristics of visual and auditory routes to
      the amygdala-a subcortical center for emotion perception-are compared across
      these stimulus classes in terms of neural dynamics, hemispheric lateralization,
      and functionality. Converging results from neuroimaging, electrophysiological,
      and lesion studies suggest the existence of an afferent route to the amygdala and
      primary visual cortex for fast and subliminal processing of coarse emotional face
      cues. We suggest that a fast route to the amygdala may also function for brief
      non-verbal vocalizations (e.g., laugh, cry), in which emotional category is
      conveyed effectively by voice tone and intensity. However, emotional prosody
      which evolves on longer time scales and is conveyed by fine-grained spectral cues
      appears to be processed via a slower, indirect cortical route. For verbal
      emotional content, the bulk of current evidence, indicating predominant left
      lateralization of the amygdala response and timing of emotional effects
      attributable to speeded lexical access, is more consistent with an indirect
      cortical route to the amygdala. Top-down linguistic modulation may play an
      important role for prioritized perception of emotions in words. Understanding the
      neural dynamics and interactions of emotion and language perception is important
      for selecting potent stimuli and devising effective training and/or treatment
      approaches for the alleviation of emotional dysfunction across a range of
      neuropsychiatric states.

PMID- 27877110
TI  - Forward Genetic Screen in Caenorhabditis elegans Suggests F57A10.2 and acp-4 As
      Suppressors of C9ORF72 Related Phenotypes.
AB  - An abnormally expanded GGGGCC repeat in C9ORF72 is the most frequent causal
      mutation associated with amyotrophic lateral sclerosis (ALS)/frontotemporal lobar
      degeneration (FTLD). Both gain-of-function (gf) and loss-of-function (lf)
      mechanisms have been involved in C9ORF72 related ALS/FTLD. The gf mechanism of
      C9ORF72 has been studied in various animal models but not in C. elegans. In the
      present study, we described mutant C9ORF72 modeling in C. elegans and report the
      finding of two suppressor genes. We made transgenes containing 9 or 29 repeats of
      GGGGCC in C9ORF72, driven by either the hsp-16 promoters or the unc-119 promoter.
      Transgenic worms were made to carry such transgenes. Phenotypic analysis of those
      animals revealed that Phsp-16::(G4C2)29::GFP transgenic animals (EAB 135)
      displayed severe paralysis by the second day of adulthood, followed by lethality,
      which phenotypes were less severe in Phsp-16::(G4C2)9::GFP transgenic animals
      (EAB242), and absent in control strains expressing empty vectors. Suppressor
      genes of this locomotor phenotype were pursued by introducing mutations with
      ethyl methanesulfonate in EAB135, screening mutant strains that moved faster than
      EAB135 by a food-ring assay, identifying mutations by whole-genome sequencing and
      testing the underlying mechanism of the suppressor genes either by employing RNA
      interference studies or C. elegans genetics. Three mutant strains, EAB164, EAB165
      and EAB167, were identified. Eight suppressor genes carrying nonsense/canonical
      splicing site mutations were confirmed, among which a nonsense mutation of
      F57A10.2/VAMP was found in all three mutant strains, and a nonsense mutation of
      acp-4/ACP2 was only found in EAB164. Knock down/out of those two genes in EAB135
      animals by feeding RNAi/introducing a known acp-4 null allele phenocopied the
      suppression of the C9ORF72 variant related movement defect in the mutant strains.
      Translational conformation in a mammalian system is required, but our worm data
      suggest that altering acp-4/ACP2 encoding lysosomal acid phosphatase may provide
      a potential therapeutic method of reducing acp-4/ACP2 levels, as opposed or
      complementary to directly reducing C9ORF72, to relieve C9ORF72-ALS phenotypes. It
      also suggests that the C9ORF72-ALS/FTLD may share a pathophysiologic mechanism
      with vesicle-associated membrane protein-associated protein B, a homolog of
      F57A10.2/VAMP, which is a proven ALS8 gene.

PMID- 27877111
TI  - Polymerizing Pyrrole Coated Poly (l-lactic acid-co-epsilon-caprolactone) (PLCL)
      Conductive Nanofibrous Conduit Combined with Electric Stimulation for Long-Range
      Peripheral Nerve Regeneration.
AB  - Electrospinning and electric stimulation (ES) are both promising methods to
      support neuron adhesion and guide extension of neurons for nerve regeneration.
      Concurrently, all studies focus on either electrospinning for conduits material
      or ES in vitro study to accelerate nerve regeneration; few work on the combined
      use of these two strategies or ES in vivo study. Therefore, this study aimed to
      investigate the abilities of direct current ES through electrospinning conductive
      polymer composites composed of polypyrrole and Poly (l-lactic acid-co-epsilon
      caprolactone) (PPY/PLCL) in peripheral nerve regeneration. PPY/PLCL composite
      conduits were synthesized by polymerizing pyrrole coated electrospun PLCL
      scaffolds. Morphologies and chemical compositions were characterized by scanning
      electron microscope and attenuated total reflection fourier transform infrared
      (ATR-FTIR) microscope. Rat pheochromocytoma 12 (PC12) cells and dorsal root
      ganglia (DRG) cells cultured on PPY/PLCL scaffolds were stimulated with 100 mV/cm
      for 4 h per day. The median neurite length and cell viability were measured in PC
      12 cells. The levels of brain-derived neurotrophic factor (BDNF), glial cell
      derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) were analyzed in DRG
      cells. In rats, 15 mm gaps of sciatic nerves were bridged using an autograft, non
      stimulated PPY/PLCL conduit and PPY/PLCL conduit stimulated with 100 mV
      potential, respectively. A 100 mV potential direct current ES was applied for 1 h
      per day at 1, 3, 5 and 7 days post-implantation. The PPY/PLCL conduits with ES
      showed a similar performance compared with the autograft group, and significantly
      better than the non-stimulated PPY/PLCL conduit group. These promising results
      show that the PPY/PLCL conductive conduits' combined use with ES has great
      potential for peripheral nerve regeneration.

PMID- 27877112
TI  - Internal Cholinergic Regulation of Learning and Recall in a Model of Olfactory
      Processing.
AB  - In the olfactory system, cholinergic modulation has been associated with contrast
      modulation and changes in receptive fields in the olfactory bulb, as well the
      learning of odor associations in olfactory cortex. Computational modeling and
      behavioral studies suggest that cholinergic modulation could improve sensory
      processing and learning while preventing pro-active interference when task
      demands are high. However, how sensory inputs and/or learning regulate incoming
      modulation has not yet been elucidated. We here use a computational model of the
      olfactory bulb, piriform cortex (PC) and horizontal limb of the diagonal band of
      Broca (HDB) to explore how olfactory learning could regulate cholinergic inputs
      to the system in a closed feedback loop. In our model, the novelty of an odor is
      reflected in firing rates and sparseness of cortical neurons in response to that
      odor and these firing rates can directly regulate learning in the system by
      modifying cholinergic inputs to the system. In the model, cholinergic neurons
      reduce their firing in response to familiar odors-reducing plasticity in the PC,
      but increase their firing in response to novel odor-increasing PC plasticity.
      Recordings from HDB neurons in awake behaving rats reflect predictions from the
      model by showing that a subset of neurons decrease their firing as an odor
      becomes familiar.

PMID- 27877113
TI  - The Effects of Realistic Synaptic Distribution and 3D Geometry on Signal
      Integration and Extracellular Field Generation of Hippocampal Pyramidal Cells and
      Inhibitory Neurons.
AB  - In vivo and in vitro multichannel field and somatic intracellular recordings are
      frequently used to study mechanisms of network pattern generation. When
      interpreting these data, neurons are often implicitly considered as
      electrotonically compact cylinders with a homogeneous distribution of excitatory
      and inhibitory inputs. However, the actual distributions of dendritic length,
      diameter, and the densities of excitatory and inhibitory input are non-uniform
      and cell type-specific. We first review quantitative data on the dendritic
      structure and synaptic input and output distribution of pyramidal cells (PCs) and
      interneurons in the hippocampal CA1 area. Second, using multicompartmental
      passive models of four different types of neurons, we quantitatively explore the
      effect of differences in dendritic structure and synaptic distribution on the
      errors and biases of voltage clamp measurements of inhibitory and excitatory
      postsynaptic currents. Finally, using the 3-dimensional distribution of dendrites
      and synaptic inputs we calculate how different inhibitory and excitatory inputs
      contribute to the generation of local field potential in the hippocampus. We
      analyze these effects at different realistic background activity levels as
      synaptic bombardment influences neuronal conductance and thus the propagation of
      signals in the dendritic tree. We conclude that, since dendrites are
      electrotonically long and entangled in 3D, somatic intracellular and field
      potential recordings miss the majority of dendritic events in some cell types,
      and thus overemphasize the importance of perisomatic inhibitory inputs and
      belittle the importance of complex dendritic processing. Modeling results also
      suggest that PCs and inhibitory neurons probably use different input integration
      strategies. In PCs, second- and higher-order thin dendrites are relatively well
      isolated from each other, which may support branch-specific local processing as
      suggested by studies of active dendritic integration. In the electrotonically
      compact parvalbumin- and cholecystokinincontaining interneurons, synaptic events
      are visible in the whole dendritic arbor, and thus the entire dendritic tree may
      form a single integrative element. Calretinin-containing interneurons were found
      to be electrotonically extended, which suggests the possibility of complex
      dendritic processing in this cell type. Our results also highlight the need for
      the integration of methods that allow the measurement of dendritic processes into
      studies of synaptic interactions and dynamics in neural networks.

PMID- 27877115
TI  - Insights into Brain Architectures from the Homological Scaffolds of Functional
      Connectivity Networks.
AB  - In recent years, the application of network analysis to neuroimaging data has
      provided useful insights about the brain's functional and structural organization
      in both health and disease. This has proven a significant paradigm shift from the
      study of individual brain regions in isolation. Graph-based models of the brain
      consist of vertices, which represent distinct brain areas, and edges which encode
      the presence (or absence) of a structural or functional relationship between each
      pair of vertices. By definition, any graph metric will be defined upon this
      dyadic representation of the brain activity. It is however unclear to what extent
      these dyadic relationships can capture the brain's complex functional
      architecture and the encoding of information in distributed networks. Moreover,
      because network representations of global brain activity are derived from
      measures that have a continuous response (i.e., interregional BOLD signals), it
      is methodologically complex to characterize the architecture of functional
      networks using traditional graph-based approaches. In the present study, we
      investigate the relationship between standard network metrics computed from
      dyadic interactions in a functional network, and a metric defined on the
      persistence homological scaffold of the network, which is a summary of the
      persistent homology structure of resting-state fMRI data. The persistence
      homological scaffold is a summary network that differs in important ways from the
      standard network representations of functional neuroimaging data: (i) it is
      constructed using the information from all edge weights comprised in the original
      network without applying an ad hoc threshold and (ii) as a summary of persistent
      homology, it considers the contributions of simplicial structures to the network
      organization rather than dyadic edge-vertices interactions. We investigated the
      information domain captured by the persistence homological scaffold by computing
      the strength of each node in the scaffold and comparing it to local graph metrics
      traditionally employed in neuroimaging studies. We conclude that the persistence
      scaffold enables the identification of network elements that may support the
      functional integration of information across distributed brain networks.

PMID- 27877114
TI  - Ontogenetic Development of Vestibulo-Ocular Reflexes in Amphibians.
AB  - Vestibulo-ocular reflexes (VOR) ensure gaze stability during locomotion and
      passively induced head/body movements. In precocial vertebrates such as
      amphibians, vestibular reflexes are required very early at the onset of locomotor
      activity. While the formation of inner ears and the assembly of sensory-motor
      pathways is largely completed soon after hatching, angular and translational/tilt
      VOR display differential functional onsets and mature with different time
      courses. Otolith-derived eye movements appear immediately after hatching, whereas
      the appearance and progressive amelioration of semicircular canal-evoked eye
      movements is delayed and dependent on the acquisition of sufficiently large
      semicircular canal diameters. Moreover, semicircular canal functionality is also
      required to tune the initially omnidirectional otolith-derived VOR. The tuning is
      due to a reinforcement of those vestibulo-ocular connections that are co
      activated by semicircular canal and otolith inputs during natural head/body
      motion. This suggests that molecular mechanisms initially guide the basic
      ontogenetic wiring, whereas semicircular canal-dependent activity is required to
      establish the spatio-temporal specificity of the reflex. While a robust VOR is
      activated during passive head/body movements, locomotor efference copies provide
      the major source for compensatory eye movements during tail- and limb-based
      swimming of larval and adult frogs. The integration of active/passive motion
      related signals for gaze stabilization occurs in central vestibular neurons that
      are arranged as segmentally iterated functional groups along rhombomere 1-8.
      However, at variance with the topographic maps of most other sensory systems, the
      sensory-motor transformation of motion-related signals occurs in segmentally
      specific neuronal groups defined by the extraocular motor output targets.

PMID- 27877116
TI  - Are Supramodality and Cross-Modal Plasticity the Yin and Yang of Brain
      Development? From Blindness to Rehabilitation.
AB  - Research in blind individuals has primarily focused for a long time on the brain
      plastic reorganization that occurs in early visual areas. Only more recently,
      scientists have developed innovative strategies to understand to what extent
      vision is truly a mandatory prerequisite for the brain's fine morphological
      architecture to develop and function. As a whole, the studies conducted to date
      in sighted and congenitally blind individuals have provided ample evidence that
      several "visual" cortical areas develop independently from visual experience and
      do process information content regardless of the sensory modality through which a
      particular stimulus is conveyed: a property named supramodality. At the same
      time, lack of vision leads to a structural and functional reorganization within
      "visual" brain areas, a phenomenon known as cross-modal plasticity. Cross-modal
      recruitment of the occipital cortex in visually deprived individuals represents
      an adaptative compensatory mechanism that mediates processing of non-visual
      inputs. Supramodality and cross-modal plasticity appears to be the "yin and yang"
      of brain development: supramodal is what takes place despite the lack of vision,
      whereas cross-modal is what happens because of lack of vision. Here we provide a
      critical overview of the research in this field and discuss the implications that
      these novel findings have for the development of educative/rehabilitation
      approaches and sensory substitution devices (SSDs) in sensory-impaired
      individuals.

PMID- 27877118
TI  - Contexts Paired with Junk Food Impair Goal-Directed Behavior in Rats:
      Implications for Decision Making in Obesogenic Environments.
AB  - The high prevalence of obesity and related metabolic diseases calls for greater
      understanding of the factors that drive excess energy intake. Calorie-dense
      palatable foods are readily available and often are paired with highly salient
      environmental cues. These cues can trigger food-seeking and consumption in the
      absence of hunger. Here we examined the effects of palatable food-paired
      environmental cues on control of instrumental food-seeking behavior. In
      Experiment 1, adult male rats received exposures to one context containing three
      "junk" foods (JFs context) and another containing chow (Chow context). Next, rats
      were food-deprived and trained to perform instrumental responses (lever-press)
      for two novel food rewards in a third, distinct context. Contextual influences on
      flexible control of food-seeking behavior were then assessed by outcome
      devaluation tests held in the JF, chow and training contexts. Devaluation was
      achieved using specific satiety and test order was counterbalanced. Rats
      exhibited goal-directed control over behavior when tested in the training and
      chow-paired contexts. Notably, performance was habitual (insensitive to
      devaluation) when tested in the JF context. In Experiment 2 we tested whether the
      impairment found in the JF context could be ameliorated by the presentation of a
      discrete auditory cue paired with the chow context, relative to a second cue
      paired with the JF context. Consistent with the results of Experiment 1, the
      devaluation effect was not significant when rats were tested in the JF context
      with the JF cue. However, presenting the chow cue increased the impact of the
      devaluation treatment leading to a robust devaluation effect. Further tests
      confirmed that performance in the chow context was goal-directed and that sensory
      specific satiety in the JF context was intact. These results show that
      environments paired with palatable foods can impair goal-directed control over
      food-seeking behavior, but that this deficit was improved by a cue paired with
      chow. This has promising implications for assisting individuals in controlling
      their eating behavior in environments designed to dysregulate it.

PMID- 27877117
TI  - General Habit Propensity Relates to the Sensation Seeking Subdomain of
      Impulsivity But Not Obesity.
AB  - According to dual-system theory, instrumental learning and performance depend on
      the balance between goal-directed and habitual action control. Overreliance on
      habits has been argued to characterize clinical conditions such as drug addiction
      or obsessive-compulsive disorder as well as obesity and excessive impulsivity. A
      tendency toward habitual action control in obesity has already been indicated in
      the food domain. However, impairments might not be restricted to eating behavior.
      This has been suggested by domain-general obesity-associated disturbances in
      executive function as well as alterations in corticostriatal circuits underlying
      the goal-directed and habitual systems. In this study we examined the balance of
      goal-directed and habitual action control in a sample of normal-weight,
      overweight, and obese participants (n = 105) using the slips-of-action test in a
      non-food context. We tested for continuous or group-based associations between
      body weight status (BMI) and the devaluation sensitivity index (DSI), a parameter
      representing the balance of the goal-directed and habitual systems in action
      control. As personality differences in the domain of impulsivity might affect
      this relationship, we also examined whether the interaction between BMI and self
      reported impulsivity, based on the UPPS Impulsive Behavior Scale, was related to
      the DSI. In addition to that, we tested for direct, i.e., weight status
      independent, relationships between UPPS subdomains of impulsivity and the DSI. We
      failed to find evidence for a relationship between weight status and sensitivity
      to devaluation as indexed by the DSI. However, independent of weight status, we
      observed lower sensitivity to devaluation in sensation seekers, a subtype of
      impulsivity. To conclude, behavioral flexibility in the sense of disturbances in
      the balance between the habitual and goal-directed systems seems to be unaffected
      by weight status in a non-food context. Consequently, stimuli and behavior might
      not be generally excessively linked in overweight or obesity. However, according
      to ceiling effects we cannot rule out subtle effects the paradigm was not able to
      disentangle. Further, future studies are needed to clarify the role of specific
      subtypes of obesity (e.g., food addiction). The indicated habit propensity in
      sensation seekers may account for previous reports of weak avoidance behavior and
      risky decision making.

PMID- 27877119
TI  - Perseverative Cognition and Health Behaviors: A Systematic Review and Meta
      Analysis.
AB  - Recent developments in stress theory have emphasized the significance of
      perseverative cognition (worry and rumination) in furthering our understanding of
      stress-disease relationships. Substantial evidence has shown that perseverative
      cognition (PC) is associated with somatic outcomes and numerous physiological
      concomitants have been identified (i.e., cardiovascular, autonomic, and endocrine
      nervous system activity parameters). However, there has been no synthesis of the
      evidence regarding the association between PC and health behaviors. This is
      important given such behaviors may also directly and/or indirectly influence
      health and disease outcomes (triggered by PC). Therefore, the aim of the current
      review was to synthesize available studies that have explored the relationship
      between worry and rumination and health behaviors (health risk: behaviors which,
      if performed, would be detrimental to health; health promoting: behaviors which,
      if performed, would be beneficial for health). A systematic review and meta
      analyses of the literature were conducted. Studies were included in the review if
      they reported the association between PC and health behavior. Studies identified
      in MEDLINE or PsycINFO (k = 7504) were screened, of which 19 studies met the
      eligibility criteria. Random-effects meta-analyses suggested increased PC was
      generally associated with increased health risk behaviors but not health
      promoting behaviors. Further analyses indicated that increases in rumination (r =
      0.122), but not reflection (r = -0.080), or worry (r = 0.048) were associated
      with health risk behaviors. In conclusion, these results showed that increases in
      PC are associated with increases in health risk behaviors (substance use, alcohol
      consumption, unhealthy eating, and smoking) that are driven primarily through
      rumination. These findings provide partial support for our hypothesis that in
      Brosschot et al.'s (2006) original perseverative cognition hypothesis, there may
      be scope for additional routes to pathogenic disease via poorer health behaviors.

PMID- 27877120
TI  - Fronto-Parietal Contributions to Phonological Processes in Successful Artificial
      Grammar Learning.
AB  - Sensitivity to regularities plays a crucial role in the acquisition of various
      linguistic features from spoken language input. Artificial grammar learning
      paradigms explore pattern recognition abilities in a set of structured sequences
      (i.e., of syllables or letters). In the present study, we investigated the
      functional underpinnings of learning phonological regularities in auditorily
      presented syllable sequences. While previous neuroimaging studies either focused
      on functional differences between the processing of correct vs. incorrect
      sequences or between different levels of sequence complexity, here the focus is
      on the neural foundation of the actual learning success. During functional
      magnetic resonance imaging (fMRI), participants were exposed to a set of syllable
      sequences with an underlying phonological rule system, known to ensure
      performance differences between participants. We expected that successful
      learning and rule application would require phonological segmentation and phoneme
      comparison. As an outcome of four alternating learning and test fMRI sessions,
      participants split into successful learners and non-learners. Relative to non
      learners, successful learners showed increased task-related activity in a fronto
      parietal network of brain areas encompassing the left lateral premotor cortex as
      well as bilateral superior and inferior parietal cortices during both learning
      and rule application. These areas were previously associated with phonological
      segmentation, phoneme comparison, and verbal working memory. Based on these
      activity patterns and the phonological strategies for rule acquisition and
      application, we argue that successful learning and processing of complex
      phonological rules in our paradigm is mediated via a fronto-parietal network for
      phonological processes.

PMID- 27877122
TI  - Changes in Neural Activity Underlying Working Memory after Computerized Cognitive
      Training in Older Adults.
AB  - Computerized cognitive training (CCT) may counter the impact of aging on
      cognition, but both the efficacy and neurocognitive mechanisms underlying CCT
      remain controversial. In this study, 35 older individuals were randomly assigned
      to Cogmed adaptive working memory (WM) CCT or an active control CCT, featuring
      five weeks of five ~40 min sessions per week. Before and after the 5-week
      intervention, event-related potentials were measured while subjects completed a
      visual n-back task with three levels of demand (0-back, 1-back, 2-back). The
      anterior P3a served as an index of directing attention and the posterior P3b as
      an index of categorization/WM updating. We hypothesized that adaptive CCT would
      be associated with decreased P3 amplitude at low WM demand and increased P3
      amplitude at high WM demand. The adaptive CCT group exhibited a training-related
      increase in the amplitude of the anterior P3a and posterior P3b in response to
      target stimuli across n-back tasks, while subjects in the active control CCT
      group demonstrated a post-training decrease in the anterior P3a. Performance did
      not differ between groups or sessions. Larger overall P3 amplitudes were strongly
      associated with better task performance. Increased post-CCT P3 amplitude
      correlated with improved task performance; this relationship was especially
      robust at high task load. Our findings suggest that adaptive WM training was
      associated with increased orienting of attention, as indexed by the P3a, and the
      enhancement of categorization/WM updating processes, as indexed by the P3b.
      Increased P3 amplitude was linked to improved performance; however. there was no
      direct association between adaptive training and improved performance.

PMID- 27877123
TI  - Mobility and Upright Posture Are Associated with Different Aspects of Cognition
      in Older Adults.
AB  - Objectives: Aging is associated with cognitive decline, including visuomotor and
      memory concerns, and with motor system changes, including gait slowing and
      stooped posture. We investigated the associations of visuomotor performance and
      episodic memory with motor system characteristics in healthy older adults.
      Methods: Neurologically healthy older adults (N = 160, aged 50-89) completed a
      battery of cognitive and motor tasks. Cognitive variables were grouped by
      principal components analysis (PCA) into two components: visuomotor performance
      and verbal episodic memory. Our primary predictor variables were two aspects of
      motor function: timed-up-and-go (TUG) speed and neck angle. Additional predictor
      variables included demographic factors (age, sex and education) and indicators of
      physical fitness (body mass index/BMI and grip strength). All seven predictor
      variables were entered stepwise into a multiple regression model for each
      cognitive component. Results: Poor visuomotor performance was best predicted by a
      combination of advanced age, high BMI and slow TUG, whereas poor verbal memory
      performance was best predicted by a combination of advanced age, male sex, low
      education and acute neck angle. Conclusions: Upright posture and mobility were
      associated with different cognitive processes, suggesting different underlying
      neural mechanisms. These results provide the first evidence for a link between
      postural alignment and cognitive functioning in healthy older adults. Possible
      causal relationships are discussed.

PMID- 27877125
TI  - An Own-Age Bias in Recognizing Faces with Horizontal Information.
AB  - Horizontal information, as a result of a selective filtering process, is
      essential in younger adults' (YA) ability to recognize human faces. Obermeyer et
      al. (2012) recently reported impaired recognition of faces with horizontal
      information in older adults (OA) suggesting age-variant processing. Two yet
      unconsidered factors (stimulus age and exposure duration) that may have
      influenced previous results, were investigated in this study. Forty-seven YA (18
      35 years) and 49 OA (62-83 years) were tested in a 2 * 2 * 2 * 2 mixed design
      with the between-subjects factors age group (YA vs. OA) and stimulus age (young
      faces vs. older faces) and the within-subjects factors filter [filtered (HF)
      faces vs. unfiltered faces (UF)] and exposure duration (0.8 s vs. 8 s). Subjects
      were presented morph videos between pairs of faces: a starting face gradually
      merged into either the previously encoded target face or a control face. As
      expected, results showed an increase in recognition sensitivity (d') with longer
      exposure duration in YA with both younger and older HF faces. OA, however, were
      unable to recognize filtered young faces not even with increased exposure
      duration. Furthermore, only elderly participants showed more accurate recognition
      with faces of their own age relative to other-age faces (own-age bias, OAB). For
      YA no OAB was observed. Filtered face recognition was significantly correlated
      with unfiltered recognition in YA but not in OA. It is concluded, that processing
      of horizontal information changes at a higher age. Presenting filtered or
      unfiltered faces both targets convergent face-specific processing only in YA but
      not in OA.

PMID- 27877124
TI  - Tau Structures.
AB  - Tau is a microtubule-associated protein that plays an important role in axonal
      stabilization, neuronal development, and neuronal polarity. In this review, we
      focus on the primary, secondary, tertiary, and quaternary tau structures. We
      describe the structure of tau from its specific residues until its conformation
      in dimers, oligomers, and larger polymers in physiological and pathological
      situations.

PMID- 27877126
TI  - Recommendations for the Use of ICT in Elderly Populations with Affective
      Disorders.
AB  - Objective: Affective disorders are frequently encountered among elderly
      populations, and the use of information and communication technologies (ICT)
      could provide an added value for their recognition and assessment in addition to
      current clinical methods. The diversity and lack of consensus in the emerging
      field of ICTs is however a strong limitation for their global use in daily
      practice. The aim of the present article is to provide recommendations for the
      use of ICTs for the assessment and management of affective disorders among
      elderly populations with or without dementia. Methods: A Delphi panel was
      organized to gather recommendations from experts in the domain. A set of initial
      general questions for the use of ICT in affective disorders was used to guide the
      discussion of the expert panel and to analyze the Strengths, Weaknesses,
      Opportunities, and Threats (SWOT) of employing ICT in elderly populations with
      affective disorders. Based on the results collected from this first round, a web
      survey was sent to local general practitioners (GPs) and to all interns in
      psychiatry in France. Results: The results of the first round revealed that ICT
      may offer very useful tools for practitioners involved in the diagnosis and
      management of affective disorders. However, the results of the web survey showed
      the interest to explain better to current and upcoming practitioners the utility
      of ICT especially for people living with dementia.

PMID- 27877121
TI  - The Indispensable Roles of Microglia and Astrocytes during Brain Development.
AB  - Glia are essential for brain functioning during development and in the adult
      brain. Here, we discuss the various roles of both microglia and astrocytes, and
      their interactions during brain development. Although both cells are
      fundamentally different in origin and function, they often affect the same
      developmental processes such as neuro-/gliogenesis, angiogenesis, axonal
      outgrowth, synaptogenesis and synaptic pruning. Due to their important
      instructive roles in these processes, dysfunction of microglia or astrocytes
      during brain development could contribute to neurodevelopmental disorders and
      potentially even late-onset neuropathology. A better understanding of the origin,
      differentiation process and developmental functions of microglia and astrocytes
      will help to fully appreciate their role both in the developing as well as in the
      adult brain, in health and disease.

PMID- 27877128
TI  - Safety Profiles of Tripterygium wilfordii Hook F: A Systematic Review and Meta
      Analysis.
AB  - Objective:Tripterygium wilfordii Hook F (TwHF) is a widely used and effective
      treatment for inflammatory diseases. There have been concerns about its toxicity
      but no adequate synthesis of the evidence for adverse events (AEs). We aimed to
      undertake a clinically informative, systematic safety profile of TwHF. Methods:
      We undertook a systematic review and meta-analysis of experimental studies and
      observational studies. We searched electronic databases and conference abstracts.
      Safety outcomes were rates of common AEs. Results: We screened 4137 abstracts for
      eligibility and included 594 studies in the analysis. The overall incidence of
      AEs was 26.7% (95% CI 24.8%, 28.8%) in 23,256 TwHF users. The estimates did vary
      markedly when stratified by specific study types. The incidence of
      gastrointestinal symptoms, adverse reproductive outcomes, adverse skin reactions,
      hematologic events and cardiovascular events were 13.3% (95% CI 11.9%, 14.9%),
      11.7% (95% CI 10.3%, 13.3%), 7.8% (95% CI 6.3-9.5%), 6.5% (95% CI 5.7-7.4 %) and
      4.9% (95% CI 1.6 %, 14.3 %), respectively. The prevalence of irregular
      menstruation (IM) was increased in patients taking TwHF compared with those given
      control (odds ratio [OR] 4.65, 95% CI 3.08 to 7.03). TwHF use has lower risk of
      weight gain (OR 0.12 [95% CI 0.04 to 0.39]) and hair loss (OR 0.37 [95% CI 0.18
      to 0.78]). Furthermore, long-term aspirin use (>6 months) has a higher AEs
      incidence (31.0% [95% CI 24.5%-38.5%]). Conclusion: Our findings suggest that
      more than one in four patients who were taking TwHF had experienced AEs. A clear
      need exists for improved understanding of contributing risk factors, as well as
      of prevention and management strategies to improve patients' tolerance for TwHF.

PMID- 27877129
TI  - Curcumin Inhibits Transforming Growth Factor beta Induced Differentiation of
      Mouse Lung Fibroblasts to Myofibroblasts.
AB  - Transforming growth factor beta (TGF-beta) induced differentiation of lung
      fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary
      fibrosis. This study aimed to evaluate the effect of curcumin on TGF-beta induced
      differentiation of lung fibroblasts to myofibroblasts and explore the underlying
      mechanism. Mouse lung fibroblasts were cultured and treated with TGF-beta2 and
      curcumin or rosiglitazone. Cell vitality was examined by MTT assay. The secretion
      of collagen-1 was assessed by ELISA. alpha smooth muscle actin (alpha-SMA) was
      visualized by immunofluorescence technique. The expression of peroxisome
      proliferator activated receptor gamma (PPAR-gamma) and platelet derived growth
      factor R beta (PDGFR-beta) was detected by PCR and Western blot analysis. We
      found that curcumin and rosiglitazone inhibited the proliferation and TGF-beta
      induced differentiation of mouse lung fibroblasts. In addition, curcumin and
      rosiglitazone inhibited collagen-1 secretion and alpha-SMA expression in mouse
      lung fibroblasts. Furthermore, curcumin and rosiglitazone upregulated PPAR-gamma
      and downregulated PDGFR-beta expression in mouse lung fibroblasts. In conclusion,
      our study reveals novel mechanism by which curcumin inhibits TGF-beta2 driven
      differentiation of lung fibroblasts to myofibroblasts. Curcumin could potentially
      be used for effective treatment of pulmonary fibrosis.

PMID- 27877127
TI  - Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of
      Mice.
AB  - Age-related changes in inhibitory neurotransmission in sensory cortex may
      underlie deficits in sensory function. Perineuronal nets (PNNs) are extracellular
      matrix components that ensheath some inhibitory neurons, particularly parvalbumin
      positive (PV+) interneurons. PNNs may protect PV+ cells from oxidative stress and
      help establish their rapid spiking properties. Although PNN expression has been
      well characterized during development, possible changes in aging sensory cortex
      have not been investigated. Here we tested the hypothesis that PNN+, PV+ and
      PV/PNN co-localized cell densities decline with age in the primary auditory
      cortex (A1). This hypothesis was tested using immunohistochemistry in two strains
      of mice (C57BL/6 and CBA/CaJ) with different susceptibility to age-related
      hearing loss and at three different age ranges (1-3, 6-8 and 14-24 months old).
      We report that PNN+ and PV/PNN co-localized cell densities decline significantly
      with age in A1 in both mouse strains. In the PNN+ cells that remain in the old
      group, the intensity of PNN staining is reduced in the C57 strain, but not the
      CBA strain. PV+ cell density also declines only in the C57, but not the CBA,
      mouse suggesting a potential exacerbation of age-effects by hearing loss in the
      PV/PNN system. Taken together, these data suggest that PNN deterioration may be a
      key component of altered inhibition in the aging sensory cortex, that may lead to
      altered synaptic function, susceptibility to oxidative stress and processing
      deficits.

PMID- 27877131
TI  - Occurrence of OsHV-1 in Crassostrea gigas Cultured in Ireland during an
      Exceptionally Warm Summer. Selection of Less Susceptible Oysters.
AB  - The occurrence of OsHV-1, a herpes virus causing mass mortality in the Pacific
      oyster Crassostrea gigas was investigated with the aim to select individuals with
      different susceptibility to the infection. Naive spat transferred to infected
      areas and juveniles currently being grown at those sites were analyzed using
      molecular and histology approaches. The survey period distinguishes itself by
      very warm temperatures reaching up to 3.5 degrees C above the average. The virus
      was not detected in the virus free area although a spread of the disease could be
      expected due to high temperatures. Overall mortality, prevalence of infection and
      viral load was higher in spat confirming the higher susceptibility in early life
      stages. OsHV-1 and oyster mortality were detected in naive spat after 15 days of
      cohabitation with infected animals. Although, infection was associated with
      mortality in spat, the high seawater temperatures could also be the direct cause
      of mortality at the warmest site. One stock of juveniles suffered an event of
      abnormal mortality that was significantly associated with OsHV-1 infection. Those
      animals were infected with a previously undescribed microvariant whereas the
      other stocks were infected with OsHV-1 MUVar. Cell lesions due to the infection
      were observed by histology and true infections were corroborated by in situ
      hybridization. Survivors from the natural outbreak were exposed to OsHV-1 MUVar
      by intramuscular injection and were compared to naive animals. The survival rate
      in previously exposed animals was significantly higher than in naive oysters.
      Results derived from this study allowed the selection of animals that might
      possess interesting characteristics for future analysis on OsHV-1 resistance.

PMID- 27877133
TI  - Decomposition of Near-Infrared Spectroscopy Signals Using Oblique Subspace
      Projections: Applications in Brain Hemodynamic Monitoring.
AB  - Clinical data is comprised by a large number of synchronously collected
      biomedical signals that are measured at different locations. Deciphering the
      interrelationships of these signals can yield important information about their
      dependence providing some useful clinical diagnostic data. For instance, by
      computing the coupling between Near-Infrared Spectroscopy signals (NIRS) and
      systemic variables the status of the hemodynamic regulation mechanisms can be
      assessed. In this paper we introduce an algorithm for the decomposition of NIRS
      signals into additive components. The algorithm, SIgnal DEcomposition base on
      Obliques Subspace Projections (SIDE-ObSP), assumes that the measured NIRS signal
      is a linear combination of the systemic measurements, following the linear
      regression model y = Ax + epsilon. SIDE-ObSP decomposes the output such that,
      each component in the decomposition represents the sole linear influence of one
      corresponding regressor variable. This decomposition scheme aims at providing a
      better understanding of the relation between NIRS and systemic variables, and to
      provide a framework for the clinical interpretation of regression algorithms,
      thereby, facilitating their introduction into clinical practice. SIDE-ObSP
      combines oblique subspace projections (ObSP) with the structure of a mean average
      system in order to define adequate signal subspaces. To guarantee smoothness in
      the estimated regression parameters, as observed in normal physiological
      processes, we impose a Tikhonov regularization using a matrix differential
      operator. We evaluate the performance of SIDE-ObSP by using a synthetic dataset,
      and present two case studies in the field of cerebral hemodynamics monitoring
      using NIRS. In addition, we compare the performance of this method with other
      system identification techniques. In the first case study data from 20 neonates
      during the first 3 days of life was used, here SIDE-ObSP decoupled the influence
      of changes in arterial oxygen saturation from the NIRS measurements, facilitating
      the use of NIRS as a surrogate measure for cerebral blood flow (CBF). The second
      case study used data from a 3-years old infant under Extra Corporeal Membrane
      Oxygenation (ECMO), here SIDE-ObSP decomposed cerebral/peripheral tissue
      oxygenation, as a sum of the partial contributions from different systemic
      variables, facilitating the comparison between the effects of each systemic
      variable on the cerebral/peripheral hemodynamics.

PMID- 27877130
TI  - Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the
      Evidence.
AB  - There is urgent need for the development of mechanistically different and less
      side-effect prone antipsychotic compounds. The endocannabinoid system has been
      suggested to represent a potential new target in this indication. While the
      chronic use of cannabis itself has been considered a risk factor contributing to
      the development of schizophrenia, triggered by the phytocannabinoid delta-9
      tetrahydrocannabinol (Delta9-THC), cannabidiol, the second most important
      phytocannabinoid, appears to have no psychotomimetic potential. Although, results
      from animal studies are inconsistent to a certain extent and seem to depend on
      behavioral paradigms, treatment duration and experimental conditions applied,
      cannabidiol has shown antipsychotic properties in both rodents and rhesus
      monkeys. After some individual treatment attempts, the first randomized, double
      blind controlled clinical trial demonstrated that in acute schizophrenia
      cannabidiol exerts antipsychotic properties comparable to the antipsychotic drug
      amisulpride while being accompanied by a superior, placebo-like side effect
      profile. As the clinical improvement by cannabidiol was significantly associated
      with elevated anandamide levels, it appears likely that its antipsychotic action
      is based on mechanisms associated with increased anandamide concentrations.
      Although, a plethora of mechanisms of action has been suggested, their potential
      relevance for the antipsychotic effects of cannabidiol still needs to be
      investigated. The clarification of these mechanisms as well as the establishment
      of cannabidiol's antipsychotic efficacy and its hopefully benign side-effect
      profile remains the subject of a number of previously started clinical trials.

PMID- 27877132
TI  - Immunophenotyping Reveals the Diversity of Human Dental Pulp Mesenchymal Stromal
      Cells In vivo and Their Evolution upon In vitro Amplification.
AB  - Mesenchymal stromal/stem cells (MSCs) from human dental pulp (DP) can be expanded
      in vitro for cell-based and regenerative dentistry therapeutic purposes. However,
      their heterogeneity may be a hurdle to the achievement of reproducible and
      predictable therapeutic outcomes. To get a better knowledge about this
      heterogeneity, we designed a flow cytometric strategy to analyze the phenotype of
      DP cells in vivo and upon in vitro expansion with stem cell markers. We focused
      on the CD31- cell population to exclude endothelial and leukocytic cells. Results
      showed that the in vivo CD31- DP cell population contained 1.4% of CD56+, 1.5% of
      CD146+, 2.4% of CD271+ and 6.3% of MSCA-1+ cells but very few Stro-1+ cells (<=
      1%). CD56+, CD146+, CD271+, and MSCA-1+ cell subpopulations expressed various
      levels of these markers. CD146+MSCA-1+, CD271+MSCA-1+, and CD146+CD271+ cells
      were the most abundant DP-MSC populations. Analysis of DP-MSCs expanded in vitro
      with a medicinal manufacturing approach showed that CD146 was expressed by about
      50% of CD56+, CD271+, MSCA-1+, and Stro-1+ cells, and MSCA-1 by 15-30% of CD56+,
      CD146+, CD271+, and Stro-1+ cells. These ratios remained stable with passages.
      CD271 and Stro-1 were expressed by <1% of the expanded cell populations.
      Interestingly, the percentage of CD56+ cells strongly increased from P1 (25%) to
      P4 (80%) both in all sub-populations studied. CD146+CD56+, MSCA-1+CD56+, and
      CD146+MSCA-1+ cells were the most abundant DP-MSCs at the end of P4. These
      results established that DP-MSCs constitute a heterogeneous mixture of cells in
      pulp tissue in vivo and in culture, and that their phenotype is modified upon in
      vitro expansion. Further studies are needed to determine whether co-expression of
      specific MSC markers confers DP cells specific properties that could be used for
      the regeneration of human tissues, including the dental pulp, with standardized
      cell-based medicinal products.

PMID- 27877135
TI  - Metabolomics of Head and Neck Cancer: A Mini-Review.
AB  - Metabolomics is used in systems biology to enhance the understanding of complex
      disease processes, such as cancer. Head and neck cancer (HNC) is an epithelial
      malignancy that arises in the upper aerodigestive tract and affects more than
      half a million people worldwide each year. Recently, significant effort has
      focused on integrating multiple "omics" technologies for oncological research. In
      particular, research has been focused on identifying tumor-specific metabolite
      profiles using different sample types (biological fluids, cells and tissues) and
      a variety of metabolomic platforms and technologies. With our current
      understanding of molecular abnormalities of HNC, the addition of metabolomic
      studies will enhance our knowledge of the pathogenesis of this disease and
      potentially aid in the development of novel strategies to prevent and treat HNC.
      In this review, we summarize the proposed hypotheses and conclusions from
      publications that reported findings on the metabolomics of HNC. In addition, we
      address the potential influence of host-microbe metabolomics in cancer. From a
      systems biology perspective, the integrative use of genomics, transcriptomics and
      proteomics will be extremely important for future translational metabolomic-based
      research discoveries.

PMID- 27877136
TI  - Novel Role of ER Stress and Autophagy in Microcystin-LR Induced Apoptosis in
      Chinese Hamster Ovary Cells.
AB  - Microcystin-LR (MC-LR) is a ubiquitous peptide that exhibits strong reproductive
      toxicity, although the mechanistic basis for such toxicity remains largely
      unknown. The present study was conducted to investigate the mechanisms underlying
      the adverse effects of exposure to MC-LR in Chinese hamster ovary (CHO) cells.
      The results showed that MC-LR inhibited the in vitro proliferation of CHO cells
      significantly, with an IC50 of 10 MUM. Moreover, MC-LR-treated CHO cells revealed
      strong induction of cell cycle arrest and apoptosis. Additionally, exposure of
      CHO cells to MC-LR resulted in excess reactive oxygen species production and
      intracellular calcium release, with resultant endoplasmic reticulum stress (ERs).
      There was also extensive accumulation of autophagic vacuoles with the highest
      concentration of MC-LR used (10 MUM). Furthermore, the expression of ERs (GRP78,
      ATF-6, PERK, IRE1, CHOP) and autophagy (Beclin1 and LC3II) proteins was
      increased, with concomitantly reduced expression of LC3I suggesting that ERs and
      autophagy were induced in CHO cells by MC-LR treatment. Conversely, pretreatment
      of CHO cells with 4-Phenyl butyric acid, the ERs inhibitor reduced the MC-LR
      induced apoptotic cell death and cellular autophagy as evidenced by the reduced
      expression of Beclin1 and LC3II. Similarly, MC-LR treatment in combination with
      an autophagy inhibitor (3-methyladenine) increased apoptotic cell death compared
      with MC-LR alone, and induced ERs via upregulating ERs proteins. The overall
      results indicated that activation of ERs and autophagy are both associated with
      MC-LR-induced apoptosis in CHO cells. ERs may be a trigger of autophagy in this
      process.

PMID- 27877134
TI  - Modulation of the Activities of Neuronal Ion Channels by Fatty Acid-Derived Pro
      Resolvents.
AB  - Progress of inflammation depends on the balance between two biological
      mechanisms: pro-inflammatory and pro-resolving processes. Many extracellular and
      intracellular molecular components including cytokines, growth factors, steroids,
      neurotransmitters, and lipidergic mediators and their receptors contribute to the
      two processes, generated from cellular participants during inflammation. Fatty
      acid-derived mediators are crucial in directing the inflammatory phase and
      orchestrating heterogeneous reactions of participants such as inflamed cells,
      innate immune cells, vascular components, innervating neurons, etc. As well as
      activating specific types of receptor molecules, lipidergic mediators can
      actively control the functions of various ion channels via direct binding and/or
      signal transduction, thereby altering cellular functions. Lipid mediators can be
      divided into two classes based on which of the two processes they promote: pro
      inflammatory, which includes prostaglandins and leukotrienes, and pro-resolving,
      which includes lipoxins, resolvins, and maresins. The research on the modulations
      of neuronal ion channels regarding the actions of the pro-inflammatory class has
      begun relatively earlier while the focus is currently expanding to cover the ion
      channel interaction with pro-resolvents. As a result, knowledge of inhibitory
      mechanisms by the pro-resolvents, historically seldom found for other known
      endogenous modulators or pro-inflammatory mediators, is accumulating particularly
      upon sensory neuronal cation channels. Diverse mechanistic explanations at
      molecular levels are being proposed and refined. Here we overviewed the
      interactions of lipidergic pro-resolvents with neuronal ion channels and outcomes
      from the interactions, focusing on transient receptor potential (TRP) ion
      channels. We also discuss unanswered hypotheses and perspectives regarding their
      interactions.

PMID- 27877137
TI  - An Extreme Mountain Ultra-Marathon Decreases the Cost of Uphill Walking and
      Running.
AB  - Purpose: To examine the effects of the world's most challenging mountain
      ultramarathon (MUM, 330 km, cumulative elevation gain of +24,000 m) on the energy
      cost and kinematics of different uphill gaits. Methods: Before (PRE) and
      immediately after (POST) the competition, 19 male athletes performed three
      submaximal 5-min treadmill exercise trials in a randomized order: walking at 5
      km.h-1, +20%; running at 6 km.h-1, +15%; and running at 8 km.h-1, +10%. During
      the three trials, energy cost was assessed using an indirect calorimetry system
      and spatiotemporal gait parameters were acquired with a floor-level high-density
      photoelectric cells system. Results: The average time of the study participants
      to complete the MUM was 129 h 43 min 48 s (range: 107 h 29 min 24 s to 144 h 21
      min 0 s). Energy costs in walking (-11.5 +/- 5.5%, P < 0.001), as well as in the
      first (-7.2 +/- 3.1%, P = 0.01) and second (-7.0 +/- 3.9%, P = 0.02) running
      condition decreased between PRE and POST, with a reduction both in the heart rate
      (-11.3, -10.0, and -9.3%, respectively) and oxygen uptake only for the walking
      condition (-6.5%). No consistent and significant changes in the kinematics
      variables were detected (P-values from 0.10 to 0.96). Conclusion: Though fatigued
      after completing the MUM, the subjects were still able to maintain their uphill
      locomotion patterns noted at PRE. The decrease (improvement) in the energy costs
      was likely due to the prolonged and repetitive walking/running, reflecting a
      generic improvement in the mechanical efficiency of locomotion after ~130 h of
      uphill locomotion rather than constraints imposed by the activity on the
      musculoskeletal structure and function.

PMID- 27877138
TI  - A Ketogenic Diet in Rodents Elicits Improved Mitochondrial Adaptations in
      Response to Resistance Exercise Training Compared to an Isocaloric Western Diet.
AB  - Purpose: Ketogenic diets (KD) can facilitate weight loss, but their effects on
      skeletal muscle remain equivocal. In this experiment we investigated the effects
      of two diets on skeletal muscle mitochondrial coupling, mitochondrial complex
      activity, markers of oxidative stress, and gene expression in sedentary and
      resistance exercised rats. Methods: Male Sprague-Dawley rats (9-10 weeks of age,
      300-325 g) were fed isocaloric amounts of either a KD (17 g/day, 5.2 kcal/g,
      20.2% protein, 10.3% CHO, 69.5% fat, n = 16) or a Western diet (WD) (20 g/day,
      4.5 kcal/g, 15.2% protein, 42.7% CHO, 42.0% fat, n = 16) for 6 weeks. During
      these 6 weeks animals were either sedentary (SED, n = 8 per diet group) or
      voluntarily exercised using resistance-loaded running wheels (EXE, n = 8 per diet
      group). Gastrocnemius was excised and used for mitochondrial isolation and
      biochemical analyses. Results: In the presence of a complex II substrate, the
      respiratory control ratio (RCR) of isolated gastrocnemius mitochondria was higher
      (p < 0.05) in animals fed the KD compared to animals fed the WD. Complex I and IV
      enzyme activity was higher (p < 0.05) in EXE animals regardless of diet. SOD2
      protein levels and GLUT4 and PGC1alpha mRNA expression were higher (p < 0.05) in
      EXE animals regardless of diet. Conclusion: Our data indicate that skeletal
      muscle mitochondrial coupling of complex II substrates is more efficient in
      chronically resistance trained rodents fed a KD. These findings may provide merit
      for further investigation, perhaps on humans.

PMID- 27877139
TI  - Corrigendum: Regularization Techniques for ECG Imaging during Atrial
      Fibrillation: A Computational Study.
AB  - [This corrects the article on p. 466 in vol. 7, PMID: 27790158.].

PMID- 27877140
TI  - 'But' Implicatures: A Study of the Effect of Working Memory and Argument
      Characteristics.
AB  - This study aimed to investigate the possible cognitive costs involved in
      processing the implicatures from but and the conclusion introducing words so and
      nevertheless. Adult participants were asked to indicate the conclusion that the
      person in the story would make, based on 'p but q' sentences constructed as
      indirect distancing contrasts. Additionally, while performing this task,
      participants' working memory was burdened with a secondary dot recall task in
      four conditions ranging from no working memory load to high load. The results
      showed that working memory load did not influence participants' performance on
      the implicature task. This finding might be interpreted to suggest that working
      memory is not involved in inferring the implicatures from but, so, and
      nevertheless. We also found that the content of the arguments played a very
      important role. Whenever a strong argument is combined with a weak argument,
      participants mostly base their conclusion on the strong argument and consequently
      ignore the conventional interpretation of but (and so and nevertheless).
      Additionally, we found an effect of axiological value, which is in line with the
      positive-negative asymmetry theory.

PMID- 27877141
TI  - Involvement of Technical Reasoning More Than Functional Knowledge in Development
      of Tool Use in Childhood.
AB  - It is well-known that even toddlers are able to manipulate tools in an
      appropriate manner according to their physical properties. The ability of
      children to make novel tools in order to solve problems is, however, surprisingly
      limited. In adults, mechanical problem solving (MPS) has been proposed to be
      supported by "technical reasoning skills," which are thought to be involved in
      every situation requiring the use of a tool (whether conventional or unusual).
      The aim of this study was to investigate the typical development of real tool use
      (RTU) skills and its link with technical reasoning abilities in healthy children.
      Three experimental tasks were adapted from those used with adults: MPS (three
      different apparatus), RTU (10 familiar tool-object pairs), and functional
      knowledge (FK; 10 functional picture matching with familiar tools previously
      used). The tasks were administered to 85 healthy children divided into six age
      groups (from 6 to 14 years of age). The results revealed that RTU (p = 0.01) and
      MPS skills improve with age, even if this improvement differs according to the
      apparatus for the latter (p < 0.01 for the Hook task and p < 0.05 for the Sloping
      task). Results also showed that MPS is a better predictor of RTU than FK, with a
      significant and greater weight (importance weight: 0.65; Estimate +/- Standard
      Error: 0.27 +/- 0.08). Ours findings suggest that RTU and technical reasoning
      develop jointly in children, independently from development of FK. In addition,
      technical reasoning appears partially operative from the age of six onward, even
      though the outcome of these skills depends of the context in which they are
      applied (i.e., the type of apparatus).

PMID- 27877142
TI  - The Proximity between Hallucination and Delusion Dimensions: An Observational,
      Analytic, Cross-Sectional, Multicentre Study.
AB  - In psychiatric classifications, hallucinations (mainly auditory hallucinations)
      are one of the fundamental criteria for establishing a schizophrenia diagnosis or
      any of the related psychotic disorder's diagnoses. The conceptual proximity
      between delusions and hallucinations was maintained until the end of the XIX
      century, with several supporters during the XX century. Their limits were not yet
      definitely defined in terms of Descriptive Psychopathology, and much less so in
      terms of biochemical and anatomical models. In this article we aimed to analyse
      the dimensions of both hallucinations and delusions in a sample of patients with
      schizophrenia and schizoaffective disorder. We also intend to find the
      determinants of the main dimensions of hallucinations. One hundred patients with
      schizophrenia (80) or schizoaffective disorder (20), 64% males, mean age 39.75,
      from the outpatient and inpatient units of the Psychiatry Department of Hospital
      de Santa Maria and the Centro Hospitalar Psiquiatrico de Lisboa were assessed by
      means of the Psychotic Symptom Rating Scales (PSYRATS) and a structured
      interview. In this study we designed an empirical based model by means of
      bivariate Spearman's rank correlation coefficient, and multivariate statistics
      (linear regression and multiple multivariate linear regression), where the main
      dimensions of hallucinations are determined by the central dimensions of
      delusions.

PMID- 27877143
TI  - Personality Development during Teacher Preparation.
AB  - Objective: The purpose of this 3-year longitudinal study was to examine pre
      service teachers' personality trajectories as measured by the IPIP Big-Five
      factor markers during teacher preparation. The relationship between students'
      personality traits, social desirability, and prior academic attainment was also
      examined. Method: This 3-year longitudinal study invited participants from the
      first year of a 4-year undergraduate (UG) pre-service teacher education program,
      the class of 2017. The sample consisted of 305 students. Results: The results
      suggest that extraversion, agreeableness, conscientiousness, emotional stability,
      and openness to experience were best represented by a non-significant
      longitudinal change in means. Results also suggest that social desirability
      predicts agreeableness and emotional stability with small to moderate effect
      sizes. Conclusion: The study concludes that no value is added to pre-service
      teachers' personality traits during 3 years of tertiary education. Furthermore,
      the data presented does not support the view that academic attainment is a good
      predictor of personality traits. Implications for educational research, theory,
      and practice are considered.

PMID- 27877144
TI  - Rhythm on Your Lips.
AB  - The Iambic-Trochaic Law (ITL) accounts for speech rhythm, grouping of sounds as
      either Iambs-if alternating in duration-or Trochees-if alternating in pitch
      and/or intensity. The two different rhythms signal word order, one of the basic
      syntactic properties of language. We investigated the extent to which Iambic and
      Trochaic phrases could be auditorily and visually recognized, when visual stimuli
      engage lip reading. Our results show both rhythmic patterns were recognized from
      both, auditory and visual stimuli, suggesting that speech rhythm has a multimodal
      representation. We further explored whether participants could match Iambic and
      Trochaic phrases across the two modalities. We found that participants auditorily
      familiarized with Trochees, but not with Iambs, were more accurate in recognizing
      visual targets, while participants visually familiarized with Iambs, but not with
      Trochees, were more accurate in recognizing auditory targets. The latter results
      suggest an asymmetric processing of speech rhythm: in auditory domain, the
      changes in either pitch or intensity are better perceived and represented than
      changes in duration, while in the visual domain the changes in duration are
      better processed and represented than changes in pitch, raising important
      questions about domain general and specialized mechanisms for speech rhythm
      processing.

PMID- 27877145
TI  - Daily Negative Work Events and Employees' Physiological and Psychological
      Reactions.
AB  - Scholars have accumulated an abundant amount of knowledge on the association
      between work stressors and employees' health and well-being. However, notions of
      the complex interplay of physiological and psychological components of stress
      reactions are still in their infancy. Building on the Allostatic Load (AL) model,
      the present study considers short-term within-person effects of negative work
      events (NWEs) on indicators of both physiological (i.e., salivary cortisol) and
      psychological distress responses (i.e., negative affect and emotional
      exhaustion). Multilevel findings from an experience sampling study with 83
      healthcare professionals suggest that reported NWEs predict employees'
      psychological but not endocrine stress responses. Results contribute to a more
      comprehensive understanding of employees' daily response patterns to occupational
      stressors.

PMID- 27877146
TI  - A Gradualist Scenario for Language Evolution: Precise Linguistic Reconstruction
      of Early Human (and Neandertal) Grammars.
AB  - In making an argument for the antiquity of language, based on comparative
      evidence, Dediu and Levinson (2013) express hope that some combinations of
      structural features will prove so conservative that they will allow deep
      linguistic reconstruction. I propose that the earliest stages of syntax/grammar
      as reconstructed in Progovac (2015a), based on a theoretical and data-driven
      linguistic analysis, provide just such a conservative platform, which would have
      been commanded also by Neandertals and the common ancestor. I provide a fragment
      of this proto-grammar, which includes flat verb-noun compounds used for naming
      and insult (e.g., rattle-snake, cry-baby, scatter-brain), and paratactic (loose)
      combinations of such flat structures (e.g., Come one, come all; You seek, you
      find). This flat, binary, paratactic platform is found in all languages, and can
      be shown to serve as foundation for any further structure building. However,
      given the degree and nature of variation across languages in elaborating syntax
      beyond this proto-stage, I propose that hierarchical syntax did not emerge once
      and uniformly in all its complexity, but rather multiple times, either within
      Africa, or after dispersion from Africa. If so, then, under the uniregional
      hypothesis, our common ancestor with Neandertals, H. heidelbergensis, could not
      have commanded hierarchical syntax, but "only" the proto-grammar. Linguistic
      reconstructions of this kind are necessary for formulating precise and testable
      hypotheses regarding language evolution. In addition to the hominin timeline,
      this reconstruction can also engage, and negotiate between, the fields of
      neuroscience and genetics, as I illustrate with one specific scenario involving
      FOXP2 gene.

PMID- 27877147
TI  - Driving and Multitasking: The Good, the Bad, and the Dangerous.
AB  - Previous research has shown that multitasking can have a positive or a negative
      influence on driving performance. The aim of this study was to determine how the
      interaction between driving circumstances and cognitive requirements of secondary
      tasks affect a driver's ability to control a car. We created a driving simulator
      paradigm where participants had to perform one of two scenarios: one with no
      traffic in the driver's lane, and one with substantial traffic in both lanes,
      some of which had to be overtaken. Four different secondary task conditions were
      combined with these driving scenarios. In both driving scenarios, using a tablet
      resulted in the worst, most dangerous, performance, while passively listening to
      the radio or answering questions for a radio quiz led to the best driving
      performance. Interestingly, driving as a single task did not produce better
      performance than driving in combination with one of the radio tasks, and even
      tended to be slightly worse. These results suggest that drivers switch to
      internally focused secondary tasks when nothing else is available during
      monotonous or repetitive driving environments. This mind wandering potentially
      has a stronger interference effect with driving than non-visual secondary tasks.

PMID- 27877148
TI  - Changes in Mood States Are Induced by Smelling Familiar and Exotic Fragrances.
AB  - Familiar fragrances usually induce positive mood states and elicit favorable
      evaluation. Relaxation is also widely thought to improve mood state. Yet
      experimental evidence on the effect of two different stimuli, fragrance smelling
      and breathing relaxation, on mood state, and fragrance evaluation is lacking.
      This study aimed to test (1) the effect of two familiar fragrances, lavender and
      myrtle, and two exotic fragrances, bergamot and ravensara, on perceived mood
      states before and after relaxation, (2) the effect of relaxation on perceived
      mood states for each fragrance, and (3) the effect of relaxation on fragrance
      evaluation as defined by adjectives. We hypothesized that mood states and
      assessment of the fragrances would differently be affected both in familiar vs.
      non-familiar fragrances and also before and after relaxation. Participants (n =
      127) completed questionnaires on their mood states at baseline (T0). They were
      then presented with each of the four fragrances separately and asked to report on
      mood state and to assess the fragrances with adjectives before (T1) and after
      (T2) breathing relaxation. Analyses of the T0-T1 delta values of mood states by
      ANOVA repeated measures and post hoc comparisons showed that mood states were
      affected by fragrance smelling with no clear differences observed between
      familiar and exotic fragrances. The same analyses of T1-T2 values showed no
      differences in mood state after breathing relaxation and fragrance smelling.
      Fragrance assessment by adjectives indicated a non-conclusive trend for familiar
      and exotic fragrances. In sum, mood states induced by the fragrance smelling
      stimulus (T0-T1) were not changed by the addition of the second stimulus of
      relaxation (T1-T2), indicating that the former stimulus was stronger than the
      latter. On the other hand, the cognitive component represented by adjective-based
      assessment of fragrances was slightly modified by the relaxation stimulus.

PMID- 27877149
TI  - Setting the Balance between the Lexical and Sublexical Pathways of Dual-Route
      Models of Reading: Insight from Atypical Dyslexia in Surgical Glioma Patients.

PMID- 27877150
TI  - The Level of Vision Necessary for Competitive Performance in Rifle Shooting:
      Setting the Standards for Paralympic Shooting with Vision Impairment.
AB  - The aim of this study was to investigate the level of vision impairment (VI) that
      would reduce performance in shooting; to guide development of entry criteria to
      visually impaired (VI) shooting. Nineteen international-level shooters without VI
      took part in the study. Participants shot an air rifle, while standing, toward a
      regulation target placed at the end of a 10 m shooting range. Cambridge
      simulation glasses were used to simulate six different levels of VI. Visual
      acuity (VA) and contrast sensitivity (CS) were assessed along with shooting
      performance in each of seven conditions of simulated impairment and compared to
      that with habitual vision. Shooting performance was evaluated by calculating each
      individual's average score in every level of simulated VI and normalizing this
      score by expressing it as a percentage of the baseline performance achieved with
      habitual vision. Receiver Operating Characteristic curves were constructed to
      evaluate the ability of different VA and CS cut-off criteria to appropriately
      classify these athletes as achieving 'expected' or 'below expected' shooting
      results based on their performance with different levels of VA and CS. Shooting
      performance remained relatively unaffected by mild decreases in VA and CS, but
      quickly deteriorated with more moderate losses. The ability of visual function
      measurements to classify shooting performance was good, with 78% of performances
      appropriately classified using a cut-off of 0.53 logMAR and 74% appropriately
      classified using a cut-off of 0.83 logCS. The current inclusion criteria for VI
      shooting (1.0 logMAR) is conservative, maximizing the chance of including only
      those with an impairment that does impact performance, but potentially excluding
      some who do have a genuine impairment in the sport. A lower level of impairment
      would include more athletes who do have a genuine impairment but would
      potentially include those who do not actually have an impairment that impacts
      performance in the sport. An impairment to CS could impact performance in the
      sport and might be considered in determining eligibility to take part in VI
      competition.

PMID- 27877151
TI  - Editorial: Using Substances to Enhance Performance: A Psychology of
      Neuroenhancement.

PMID- 27877152
TI  - Bridging the Gap between the Lab and the Clinic: Psychopathology's Grand
      Challenge.

PMID- 27877153
TI  - Computational Psychometrics Meets Hollywood: The Complexity in Emotional
      Storytelling.
AB  - Expressions of emotions are pervasive in media, especially in movies. In this
      article, we focus on the emotional relationships of movie characters in narrative
      thought and emotional storytelling. Several studies examine emotion elicitation
      through movies, but there is a gap in scientific literature and in the practice
      to quantitatively consider emotions among the characters of a movie story, which
      in turn provide the basis of spectator emotion elicitation. Some might argument
      that the ultimate purpose of a movie is to elicit emotions in the viewers;
      however, we are highlighting that the path to emotional stimulation entails
      emotions among the characters composing a narrative and manipulating to enable
      the effective elicitation of viewers' emotions. Here we provided and tested an
      effective quantitative method for analyzing these relationships in emotional
      networks, which allow for a clear understanding of the effects of story changes
      on movie perceptions and pleasantness.

PMID- 27877155
TI  - Weak and Saturable Protein-Surfactant Interactions in the Denaturation of Apo
      alpha-Lactalbumin by Acidic and Lactonic Sophorolipid.
AB  - Biosurfactants are of growing interest as sustainable alternatives to fossil-fuel
      derived chemical surfactants, particularly for the detergent industry. To realize
      this potential, it is necessary to understand how they affect proteins which they
      may encounter in their applications. However, knowledge of such interactions is
      limited. Here, we present a study of the interactions between the model protein
      apo-alpha-lactalbumin (apo-aLA) and the biosurfactant sophorolipid (SL) produced
      by the yeast Starmerella bombicola. SL occurs both as an acidic and a lactonic
      form; the lactonic form (lactSL) is sparingly soluble and has a lower critical
      micelle concentration (cmc) than the acidic form [non-acetylated acidic
      sophorolipid (acidSL)]. We show that acidSL affects apo-aLA in a similar way to
      the related glycolipid biosurfactant rhamnolipid (RL), with the important
      difference that RL is also active below the cmc in contrast to acidSL. Using
      isothermal titration calorimetry data, we show that acidSL has weak and saturable
      interactions with apo-aLA at low concentrations; due to the relatively low cmc of
      acidSL (which means that the monomer concentration is limited to ca. 0-1 mM SL),
      it is only possible to observe interactions with monomeric acidSL at high apo-aLA
      concentrations. However, the denaturation kinetics of apo-aLA in the presence of
      acidSL are consistent with a collaboration between monomeric and micellar
      surfactant species, similar to RL and non-ionic or zwitterionic surfactants.
      Inclusion of diacetylated lactonic sophorolipid (lactSL) as mixed micelles with
      acidSL lowers the cmc and this effectively reduces the rate of unfolding,
      emphasizing that SL like other biosurfactants is a gentle anionic surfactant. Our
      data highlight the potential of these biosurfactants for future use in the
      detergent and pharmaceutical industry.

PMID- 27877154
TI  - Immununochemical Markers of the Amyloid Cascade in the Hippocampus in Motor
      Neuron Diseases.
AB  - BACKGROUND: Several findings suggest that the amyloid precursor protein (APP) and
      the amyloid cascade may play a role in motor neuron disease (MND). OBJECTIVE:
      Considering that dementia is one of the most frequent non-motor symptoms in
      amyotrophic lateral sclerosis (ALS) and that hippocampus is one of the brain
      areas with greater presence of amyloid-related changes in neurodegenerative
      diseases, our aim was to analyze the molecular markers of the amyloid cascade of
      APP in pathology studies of the hippocampus of autopsied patients with ALS and
      ALS-frontotemporal dementia (FTD). METHODS: We included nine patients with MND
      and four controls. Immunohistochemical studies and confocal microscopy were used
      to analyze the expression of APP, TDP-43, pho-TDP-43, Abeta, APP intracellular
      cytoplasmatic domain (AICD) peptide, Fe65 protein, and pho-TAU in the hippocampus
      of seven patients with ALS, two patients with ALS-FTD, and four controls. These
      findings were correlated with clinical data. RESULTS: Patients displayed
      increased expression of APP and Abeta peptide. The latter was correlated with
      cytoplasmic pho-TDP-43 expression. We also found decreased Fe65 expression. A
      parallel increase in AICD expression was not found. Patients showed increased
      expression of pho-TAU in the hippocampus. Findings were similar in patients with
      ALS and those with ALS-FTD, though more marked in the latter group. CONCLUSION:
      Post-mortem analyses showed that the amyloid cascade is activated in the
      hippocampus of patients with MND and correlated with cytoplasmic pho-TDP-43
      expression. The number of intracellular or extracellular aggregates of Abeta
      peptides was not significant.

PMID- 27877156
TI  - A Chitosan Coating Containing Essential Oil from Origanum vulgare L. to Control
      Postharvest Mold Infections and Keep the Quality of Cherry Tomato Fruit.
AB  - The efficacy of an edible chitosan coating (CHI; 4 mg/mL) and Origanum vulgare L.
      essential oil (OVEO; 1.25 MUL/mL) for maintaining the quality of cherry tomato
      fruit during storage at room (25 degrees C; 12 days) and cold (12 degrees C; 24
      days) temperatures was assessed. CHI and OVEO in combination showed in vitro
      fungicidal effects against R. stolonifer and Aspergillus niger. CHI-OVEO coating
      reduced the incidence of black mold and soft rot caused by these fungi in
      artificially contaminated cherry tomato fruit during storage at both
      temperatures. CHI-OVEO coating delayed the appearance of the first visible signs
      of black mold and soft rot in artificially contaminated cherry tomato fruit
      stored at room temperature by 6 days and by more than 9 days in those stored at
      cold temperature. At the end of storage at room and cold temperature fruit coated
      with CHI-OVEO showed higher firmness (>2 N/mm) and lower weight loss (>2%)
      compared to uncoated tomato fruit. CHI-OVEO coating delayed the decrease of
      lycopene, ascorbic citric acid, glucose and fructose during the storage time
      assessed at room or cold temperatures. The increase of catechin, myricetin,
      caffeic and syringic acids was higher (1-9 mg/g) in cherry tomato fruit coated
      with CHI-OVEO compared to uncoated fruit during the storage at both temperatures
      studied. CHI-OVEO coating is a feasible treatment for maintaining the storage
      quality of cherry tomato fruit.

PMID- 27877157
TI  - Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the
      agr Quorum Sensing System.
AB  - Staphylococci are associated with both humans and animals. While most are non
      pathogenic colonizers, Staphylococcus aureus is an opportunistic pathogen capable
      of causing severe infections. S. aureus virulence is controlled by the agr quorum
      sensing system responding to secreted auto-inducing peptides (AIPs) sensed by
      AgrC, a two component histidine kinase. agr loci are found also in other
      staphylococcal species and for Staphylococcus epidermidis, the encoded AIP
      represses expression of agr regulated virulence genes in S. aureus. In this study
      we aimed to better understand the interaction between staphylococci and S.
      aureus, and show that this interaction may eventually lead to the identification
      of new anti-virulence candidates to target S. aureus infections. Here we show
      that culture supernatants of 37 out of 52 staphylococcal isolates representing 17
      different species inhibit S. aureus agr. The dog pathogen, Staphylococcus
      schleiferi, expressed the most potent inhibitory activity and was active against
      all four agr classes found in S. aureus. By employing a S. aureus strain encoding
      a constitutively active AIP receptor we show that the activity is mediated via
      agr. Subsequent cloning and heterologous expression of the S. schleiferi AIP in
      S. aureus demonstrated that this molecule was likely responsible for the
      inhibitory activity, and further proof was provided when pure synthetic S.
      schleiferi AIP was able to completely abolish agr induction of an S. aureus
      reporter strain. To assess impact on S. aureus virulence, we co-inoculated S.
      aureus and S. schleiferi in vivo in the Galleria mellonella wax moth larva, and
      found that expression of key S. aureus virulence factors was abrogated. Our data
      show that the S. aureus agr locus is highly responsive to other staphylococcal
      species suggesting that agr is an inter-species communication system. Based on
      these results we speculate that interactions between S. aureus and other
      colonizing staphylococci will significantly influence the ability of S. aureus to
      cause infection, and we propose that other staphylococci are potential sources of
      compounds that can be applied as anti-virulence therapy for combating S. aureus
      infections.

PMID- 27877158
TI  - Ultrastructure and Viral Metagenome of Bacteriophages from an Anaerobic Methane
      Oxidizing Methylomirabilis Bioreactor Enrichment Culture.
AB  - With its capacity for anaerobic methane oxidation and denitrification, the
      bacterium Methylomirabilis oxyfera plays an important role in natural ecosystems.
      Its unique physiology can be exploited for more sustainable wastewater treatment
      technologies. However, operational stability of full-scale bioreactors can
      experience setbacks due to, for example, bacteriophage blooms. By shaping
      microbial communities through mortality, horizontal gene transfer, and metabolic
      reprogramming, bacteriophages are important players in most ecosystems. Here, we
      analyzed an infected Methylomirabilis sp. bioreactor enrichment culture using
      (advanced) electron microscopy, viral metagenomics and bioinformatics. Electron
      micrographs revealed four different viral morphotypes, one of which was observed
      to infect Methylomirabilis cells. The infected cells contained densely packed ~55
      nm icosahedral bacteriophage particles with a putative internal membrane. Various
      stages of virion assembly were observed. Moreover, during the bacteriophage
      replication, the host cytoplasmic membrane appeared extremely patchy, which
      suggests that the bacteriophages may use host bacterial lipids to build their own
      putative internal membrane. The viral metagenome contained 1.87 million base
      pairs of assembled viral sequences, from which five putative complete viral
      genomes were assembled and manually annotated. Using bioinformatics analyses, we
      could not identify which viral genome belonged to the Methylomirabilis- infecting
      bacteriophage, in part because the obtained viral genome sequences were novel and
      unique to this reactor system. Taken together these results show that new
      bacteriophages can be detected in anaerobic cultivation systems and that the
      effect of bacteriophages on the microbial community in these systems is a topic
      for further study.

PMID- 27877160
TI  - Antibacterial Potential of Jatropha curcas Synthesized Silver Nanoparticles
      against Food Borne Pathogens.
AB  - The aqueous leaf extract of Jatropha curcas was used for the synthesis of silver
      nanoparticles (Jc-AgNps) which were further evaluated for its antibacterial
      potential against food borne pathogens. J. curcas leaf extract could synthesize
      stable silver nanoparticles (Zeta potential: -23.4 mV) with absorption band at
      430 nm. Fourier transform infrared spectroscopy indicated various biological
      compounds responsible for capping and stabilizing Jc-AgNps in suspension, while
      the presence of silver was authenticated by scanning electron microscopy (SEM)
      equipped with energy-dispersive X-ray. Jc-AgNps were confirmed to be uniform in
      shape, size and behavior through dynamic light scattering, transmission electron
      microscopy (TEM), X-ray diffraction, SEM, and atomic force microscopy (AFM)
      analysis. To investigate the antibacterial activity, disk diffusion and
      microplate dilution assays were performed and zone of inhibition (ZOI) as well as
      minimum inhibitory/bactericidal concentrations (MIC/MBCs) were evaluated against
      selected bacterial strains. Overall results showed that Escherichia coli (ZOI: 23
      mm, MBC: 0.010 mg/ml) was the most sensitive organism, whereas Staphylococcus
      aureus (ZOI: 14.66 mm, MBC: 0.041 mg/ml) and Salmonella enterica (ZOI: 16.66 mm,
      MBC: 0.041 mg/ml) were the least sensitive against Jc-AgNps. The detailed
      microscopic investigations using SEM, TEM, and AFM were performed to understand
      the antibacterial impacts of Jc-AgNps against Listeria monocytogenes. SEM and TEM
      analysis showed the clear deformation and disintegration of treated L.
      monocytogenes cells, whereas AFM established a decrease in the height and cell
      surface roughness (root mean square value) in the treated L. monocytogenes.

PMID- 27877159
TI  - Efficacy of Antibacterial Peptides Against Peptide-Resistant MRSA Is Restored by
      Permeabilization of Bacteria Membranes.
AB  - Clinical application of antimicrobial peptides (AMPs), as with conventional
      antibiotics, may be compromised by the development of bacterial resistance. This
      study investigated AMP resistance in methicillin resistant Staphylococcus aureus,
      including aspects related to the resilience of the resistant bacteria toward the
      peptides, the stability of resistance when selection pressures are removed, and
      whether resistance can be overcome by using the peptides with other membrane
      permeabilising agents. Genotypically variant strains of S. aureus became equally
      resistant to the antibacterial peptides melittin and bac8c when grown in sub
      lethal concentrations. Subculture of a melittin-resistant strain without melittin
      for 8 days lowered the minimal lethal concentration of the peptide from 170 MUg
      ml-1 to 30 MUg ml-1. Growth for 24 h in 12 MUg ml-1 melittin restored the MLC to
      100 MUg ml-1. Flow cytometry analysis of cationic fluorophore binding to melittin
      naive and melittin-resistant bacteria revealed that resistance coincided with
      decreased binding of cationic molecules, suggesting a reduction in nett negative
      charge on the membrane. Melittin was haemolytic at low concentrations but the
      truncated analog of melittin, mel12-26, was confirmed to lack haemolytic
      activity. Although a previous report found that mel12-26 retained full
      bactericidal activity, we found it to lack significant activity when added to
      culture medium. However, electroporation in the presence of 50 MUg ml-1 of mel12
      26, killed 99.3% of the bacteria. Similarly, using a low concentration of the non
      ionic detergent Triton X-100 to permeabilize bacteria to mel12-26 markedly
      increased its bactericidal activity. The observation that bactericidal activity
      of the non-membranolytic peptide mel12-26 was enhanced when the bacterial
      membrane was permeablized by detergents or electroporation, suggests that its
      principal mechanism in reducing bacterial survival may be through interaction
      with intracellular organelles or processes. Additionally, our results showed that
      the haemolytic peptide bac8c, had increased antibacterial activity at non
      haemolytic concentrations when used with membrane-permeabilizing surfactants.

PMID- 27877161
TI  - An Enrichment of CRISPR and Other Defense-Related Features in Marine Sponge
      Associated Microbial Metagenomes.
AB  - Many marine sponges are populated by dense and taxonomically diverse microbial
      consortia. We employed a metagenomics approach to unravel the differences in the
      functional gene repertoire among three Mediterranean sponge species, Petrosia
      ficiformis, Sarcotragus foetidus, Aplysina aerophoba and seawater. Different
      signatures were observed between sponge and seawater metagenomes with regard to
      microbial community composition, GC content, and estimated bacterial genome size.
      Our analysis showed further a pronounced repertoire for defense systems in sponge
      metagenomes. Specifically, clustered regularly interspaced short palindromic
      repeats, restriction modification, DNA phosphorothioation and phage growth
      limitation systems were enriched in sponge metagenomes. These data suggest that
      defense is an important functional trait for an existence within sponges that
      requires mechanisms to defend against foreign DNA from microorganisms and
      viruses. This study contributes to an understanding of the evolutionary arms race
      between viruses/phages and bacterial genomes and it sheds light on the bacterial
      defenses that have evolved in the context of the sponge holobiont.

PMID- 27877162
TI  - Genome Sequence of Pseudomonas koreensis CRS05-R5, an Antagonistic Bacterium
      Isolated from Rice Paddy Field.

PMID- 27877163
TI  - Diversification of the vacAs1m1 and vacAs2m2 Strains of Helicobacter pylori in
      Meriones unguiculatus.
AB  - The bacterium Helicobacter pylori exhibits great genetic diversity, and the
      pathogenic roles of its virulence factors have been widely studied. However, the
      evolutionary dynamics of H. pylori strains during stomach colonization are not
      well-characterized. Here, we analyzed the microevolutionary dynamics of the
      toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination
      of both strains in an animal model over time. Meriones unguiculatus were
      inoculated with the following bacteria: group 1-toxigenic strain
      vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2-non-toxigenic strain
      vacAs2m2/cagA+/cagE+/babA2+; ST2901, and group 3-both strains. The gerbils were
      euthanized at different time points (3, 6, 12, and 18 months). In group 1,
      genetic alterations were observed at 6 and 12 months. With the combination of
      both strains, group 3 also exhibited genetic alterations at 3 and 18 months;
      moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence
      types (STs) were reported in the PubMLST database for H. pylori. Synonymous and
      non-synonymous mutations were analyzed and associated with alterations in amino
      acids. Microevolutionary analysis of the STs (PHYLOViZ) identified in each group
      revealed many mutational changes in the toxigenic (vacAs1m1) and non-toxigenic
      (vacAs2m2) strains. Phylogenetic assessments (eBURST) did not reveal clonal
      complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a
      combination of toxigenic and non-toxigenic strains acquired genetic material by
      recombination. The allelic combination, vacAs2m1, displayed the best adaptation
      in the animal model over time, and a chimera, m1-m2, was also identified, which
      confirmed previous reports.

PMID- 27877164
TI  - Distribution of Native Lactic Acid Bacteria in Wineries of Queretaro, Mexico and
      Their Resistance to Wine-Like Conditions.
AB  - Native lactic acid bacteria (LAB) are capable of growing during winemaking,
      thereby strongly affecting wine quality. The species of LAB present in musts,
      wines during malolactic fermentation (MLF), and barrels/filters were investigated
      in wineries from the emerging wine region of Queretaro, Mexico using multiplex
      PCR and culture. The resistance to wine-like conditions (WLC): ethanol (10, 12,
      and 13%), SO2 (30 mg?l-1), and low pH (3.5) of native LAB strains was also
      studied. Five species were detected within 61 samples obtained: Oenococcus oeni,
      Lactobacillus plantarum, Pediococcus parvulus, Lactobacillus hilgardi, and
      Lactobacillus brevis. Four species (excepting L. brevis) were found in must; O.
      oeni and P. parvulus were ubiquitous in wine and L. plantarum and L. brevis were
      mainly present at the initial stage of MLF, while L. hilgardii was mostly
      detected at the advanced stage. Furthermore, some species detected in
      barrel/filter, prove them to be hazardous reservoirs. From 822 LAB isolates, only
      119 resisted WLC with 10% ethanol; the number of strains able to grow in WLC with
      13% ethanol decreased approximately by 50%, O. oeni being the most versatile
      species with 65% of resistant isolates, while Lactobacillus spp. and P. parvulus
      were the most strongly affected, especially those recovered from barrel/filter,
      with less than 10% of resistant isolates. This study evidences the presence of
      local strains able to be used as starter cultures, and also enabled the
      assessment of the risks derived from the presence of spoilage LAB strains
      resistant to WLC.

PMID- 27877165
TI  - Different Flour Microbial Communities Drive to Sourdoughs Characterized by
      Diverse Bacterial Strains and Free Amino Acid Profiles.
AB  - This work aimed to investigate whether different microbial assemblies in flour
      may influence the microbiological and biochemical characteristics of traditional
      sourdough. To reach this purpose, members of lactic acid bacteria,
      enterobacteria, and yeasts were isolated from durum wheat flour. Secondly, the
      isolated microorganisms (Pediococcus pentosaceus, Saccharomyces cerevisiae,
      Pantoea agglomerans, and Escherichia hermannii) were inoculated in doughs
      prepared with irradiated flour (gamma rays at 10 kGy), so that eight different
      microbial assemblies were obtained. Two non-inoculated controls were prepared,
      one of which (C-IF) using irradiated flour and the other (C) using non-irradiated
      flour. As shown by plate counts, irradiation of flour caused total inactivation
      of yeasts and a decrease of all the other microbial populations. However,
      acidification occurred also in the dough C-IF, due to metabolic activity of P.
      pentosaceus that had survived irradiation. After six fermentations, P.
      pentosaceus was the dominant lactic acid bacterium species in all the sourdoughs
      produced with irradiated flour (IF). Yet, IF-based sourdoughs broadly differed
      from each other in terms of strains of P. pentosaceus, probably due to the
      different microorganisms initially inoculated. Quantitative and qualitative
      differences of free amino acids concentration were found among the sourdoughs,
      possibly because of different microbial communities. In addition, as shown by
      culture-independent analysis (16S metagenetics), irradiation of flour lowered and
      modified microbial diversity of sourdough ecosystem.

PMID- 27877166
TI  - A Narrow pH Range Supports Butanol, Hexanol, and Octanol Production from Syngas
      in a Continuous Co-culture of Clostridium ljungdahlii and Clostridium kluyveri
      with In-Line Product Extraction.
AB  - Carboxydotrophic bacteria (CTB) have received attention due to their ability to
      synthesize commodity chemicals from producer gas and synthesis gas (syngas). CTB
      have an important advantage of a high product selectivity compared to chemical
      catalysts. However, the product spectrum of wild-type CTB is narrow. Our
      objective was to investigate whether a strategy of combining two wild-type
      bacterial strains into a single, continuously fed bioprocessing step would be
      promising to broaden the product spectrum. Here, we have operated a syngas
      fermentation process with Clostridium ljungdahlii and Clostridium kluyveri with
      in-line product extraction through gas stripping and product condensing within
      the syngas recirculation line. The main products from C. ljungdahlii fermentation
      at a pH of 6.0 were ethanol and acetate at net volumetric production rates of
      65.5 and 431 mmol C.L-1.d-1, respectively. An estimated 2/3 of total ethanol
      produced was utilized by C. kluyveri to chain elongate with the reverse beta
      oxidation pathway, resulting in n-butyrate and n-caproate at net rates of 129 and
      70 mmol C.L-1.d-1, respectively. C. ljungdahlii likely reduced the produced
      carboxylates to their corresponding alcohols with the reductive power from
      syngas. This resulted in the longer-chain alcohols n-butanol, n-hexanol, and n
      octanol at net volumetric production rates of 39.2, 31.7, and 0.045 mmol C.L-1.d
      1, respectively. The continuous production of the longer-chain alcohols occurred
      only within a narrow pH spectrum of 5.7-6.4 due to the pH discrepancy between the
      two strains. Regardless whether other wild-type strains could overcome this pH
      discrepancy, the specificity (mol carbon in product per mol carbon in all other
      liquid products) for each longer-chain alcohol may never be high in a single
      bioprocessing step. This, because two bioprocesses compete for intermediates
      (i.e., carboxylates): (1) chain elongation; and (2) biological reduction. This
      innate competition resulted in a mixture of n-butanol and n-hexanol with traces
      of n-octanol.

PMID- 27877168
TI  - Characterization of Electricity Generated by Soil in Microbial Fuel Cells and the
      Isolation of Soil Source Exoelectrogenic Bacteria.
AB  - Soil has been used to generate electrical power in microbial fuel cells (MFCs)
      and exhibited several potential applications. This study aimed to reveal the
      effect of soil properties on the generated electricity and the diversity of soil
      source exoelectrogenic bacteria. Seven soil samples were collected across China
      and packed into air-cathode MFCs to generate electricity over a 270 days period.
      The Fe(III)-reducing bacteria in soil were enriched and sequenced by Illumina
      pyrosequencing. Culturable strains of Fe(III)-reducing bacteria were isolated and
      identified phylogenetically. Their exoelectrogenic ability was evaluated by
      polarization measurement. The results showed that soils with higher organic
      carbon (OC) content but lower soil pH generated higher peak voltage and charge.
      The sequencing of Fe(III)-reducing bacteria showed that Clostridia were dominant
      in all soil samples. At the family level, Clostridiales Family XI incertae sedis
      were dominant in soils with lower OC content but higher pH (>8), while
      Clostridiaceae, Lachnospiraceae, and Planococcaceae were dominant in soils with
      higher OC content but lower pH. The isolated culturable strains were allied
      phylogenetically to 15 different species, of which 11 were Clostridium. The
      others were Robinsoniella peoriensis, Hydrogenoanaerobacterium saccharovorans,
      Eubacterium contortum, and Oscillibacter ruminantium. The maximum power density
      generated by the isolates in the MFCs ranged from 16.4 to 28.6 mW m-2. We
      concluded that soil OC content had the most important effect on power generation
      and that the Clostridiaceae were the dominant exoelectrogenic bacterial group in
      soil. This study might lead to the discovery of more soil source exoelectrogenic
      bacteria species.

PMID- 27877169
TI  - Draft Genome Sequence of a Multi-Metal Resistant Bacterium Pseudomonas putida ATH
      43 Isolated from Greenwich Island, Antarctica.

PMID- 27877167
TI  - Polycyclic Aromatic Hydrocarbon-Induced Changes in Bacterial Community Structure
      under Anoxic Nitrate Reducing Conditions.
AB  - Although bacterial anaerobic degradation of mono-aromatic compounds has been
      characterized in depth, the degradation of polycyclic aromatic hydrocarbons
      (PAHs) such as naphthalene has only started to be understood in sulfate reducing
      bacteria, and little is known about the anaerobic degradation of PAHs in nitrate
      reducing bacteria. Starting from a series of environments which had suffered
      different degrees of hydrocarbon pollution, we used most probable number (MPN)
      enumeration to detect and quantify the presence of bacterial communities able to
      degrade several PAHs using nitrate as electron acceptor. We detected the presence
      of a substantial nitrate reducing community able to degrade naphthalene, 2
      methylnaphthalene (2MN), and anthracene in some of the sites. With the aim of
      isolating strains able to degrade PAHs under denitrifying conditions, we set up a
      series of enrichment cultures with nitrate as terminal electron acceptor and PAHs
      as the only carbon source and followed the changes in the bacterial communities
      throughout the process. Results evidenced changes attributable to the imposed
      nitrate respiration regime, which in several samples were exacerbated in the
      presence of the PAHs. The presence of naphthalene or 2MN enriched the community
      in groups of uncultured and poorly characterized organisms, and notably in the
      Acidobacteria uncultured group iii1-8, which in some cases was only a minor
      component of the initial samples. Other phylotypes selected by PAHs in these
      conditions included Bacilli, which were enriched in naphthalene enrichments.
      Several nitrate reducing strains showing the capacity to grow on PAHs could be
      isolated on solid media, although the phenotype could not be reproduced in liquid
      cultures. Analysis of known PAH anaerobic degradation genes in the original
      samples and enrichment cultures did not reveal the presence of PAH-related nmsA
      like sequences but confirmed the presence of bssA-like genes related to anaerobic
      toluene degradation. Altogether, our results suggest that PAH degradation by
      nitrate reducing bacteria may require the contribution of different strains,
      under culture conditions that still need to be defined.

PMID- 27877170
TI  - Comparison of S. stercoralis Serology Performed on Dried Blood Spots and on
      Conventional Serum Samples.
AB  - Background: Dried blood spots (DBS) are used for epidemiological surveys on
      infectious diseases in settings where limited resources are available. In fact,
      DBS can help to overcome logistic difficulties for the collection, transport and
      storage of biological specimens. Objective: To evaluate the accuracy of
      Strongyloides stercoralis serology performed on DBS. Methods: A survey was
      proposed to children attending a school in the village of Borbon, Ecuador, and to
      their parents/guardians. Each participant gave consent to the collection of both
      serum and DBS specimens. DBS absorbed on filter papers were analyzed with a
      commercially available ELISA test for S. stercoralis antibodies, as well as with
      standard serology. The agreement between the two methods was assessed through the
      Cohen's kappa coefficient. Results: The study sample was composed of 174 children
      and 61 adults, for a total of 235 serum and 235 DBS samples. The serology was
      positive in 31/235 (13%) serum samples, and in 27/235 (11%) DBS: 4 samples
      resulted discordant (positive at standard serology). Cohen's kappa coefficient
      was 0.921 (95% CI 0.845 - 0.998), indicating a high rate of concordance.
      Conclusion: DBS are suitable for in field-surveys requiring serological testing
      for S. stercoralis.

PMID- 27877171
TI  - Distinct Factors Shape Aquatic and Sedimentary Microbial Community Structures in
      the Lakes of Western China.
AB  - Little is known about the relative importance of spatial and environmental
      factors to structuring aquatic and sedimentary microbial biogeography in lakes.
      Here, we investigated the microbial community composition (MCC) of the water (n =
      35) and sediment (n = 35) samples from 16 lakes in western China (salinity:
      freshwater to salt saturation; pairwise geographical distance: 9-2027 km) using
      high-throughput sequencing and evaluated the relative importance of spatial and
      environmental factors to microbial (including total, abundant, and rare)
      distributions. Our results showed that spatial factors were more important than
      environmental factors in shaping the biogeography of aquatic and sedimentary
      microbial communities in the studied lakes, and spatial factors on abundant
      microbial community was stronger than that on the total/rare microbial
      communities. Moreover, sedimentary rare MCC might be more sensitive to
      environmental factors than its aquatic counterpart. Such different biogeography
      responses of total, abundant, and rare communities to environmental and spatial
      factors could be ascribed to different physiochemical properties between water
      and sediment. Collectively, this study expands our understanding of factors
      shaping microbial biogeography of total, abundant, and rare communities between
      waters and sediments of lakes.

PMID- 27877172
TI  - Regulated Inflammation and Lipid Metabolism in Colon mRNA Expressions of Obese
      Germfree Mice Responding to Enterobacter cloacae B29 Combined with the High Fat
      Diet.
AB  - Increased evidences have demonstrated that gut microbiota targeted diet
      intervention can alleviate obesity and related metabolic disorders. The
      underlying mechanism of interactions among diet, microbiota, and host still
      remains unclear. Enterobacter cloacae B29, an endotoxin-producing strain
      dominated in the gut of a morbidly obese volunteer (weight 174.8 kg, BMI 58.8 kg
      m-2) was isolated and transplanted to germfree mice (inoculated 1010 cells of B29
      per day for 1 week). Using deep mRNA sequencing technology, we compared different
      gene expression profiles in the colon samples of the germfree mice treated
      with/without B29 and/or high fat diet (HFD) for 16 weeks and identified 279
      differential expressed genes in total, including up-regulated genes Apoa4 (fold
      change, 2.77), Ido1 (2.66), Cyp4a10 (7.01), and down-regulated genes Cyp2e1
      (0.11), Cyp26b1 (0.34), Akr1b7 (0.42), Adipoq (0.36), Cyp1a1 (0.11), Apoa1
      (0.44), Npc1l1 (0.37), Tff2 (0.13), Apoc1 (0.30), Ctla2a (0.34), Mttp (0.49), Lpl
      (0.48). Fifty-nine GO biological processes and five KEGG pathways, particularly
      the peroxisome proliferator-activated receptors signaling pathway, were
      significantly enriched in response to HFD+B29, which were mainly relevant to
      inflammation and the metabolism of lipid, lipoprotein, and sterols. These
      functional changes were consistent with the developed obesity, insulin
      resistance, and aggravated inflammatory conditions of the HFD+B29 mice. This work
      provides insight into the gene expression changes in response to HFD+B29, helping
      to understand the mechanism of the interactions among HFD, B29 and the germfree
      mice.

PMID- 27877174
TI  - DNA Methyltransferase Inhibitor Promotes Human CD4+CD25hFOXP3+ Regulatory T
      Lymphocyte Induction under Suboptimal TCR Stimulation.
AB  - The "master transcription factor" FOXP3 regulates the differentiation,
      homeostasis, and suppressor function of CD4+ regulatory T (Treg) cells, which are
      critical in maintaining immune tolerance. Epigenetic regulation of FOXP3
      expression has been demonstrated to be important to Treg cell development, but
      the induction of human Treg cells through epigenetic modification has not been
      clearly described. We report that the combination of the DNA methyltransferase
      inhibitor 5-azacytidine (5-Aza) and suboptimal T cell receptor (TCR) stimulation
      promoted CD4+CD25hFOXP3+ T cell induction from human CD4+CD25- T cells. 5-Aza
      treatment enhanced the expression of Treg cell signature genes, such as CD25,
      FOXP3, CTLA-4, and GITR, in CD4+CD25h cells. Moreover, 5-Aza-treated CD4+CD25h T
      cells showed potent suppressive activity in a cell contact-dependent manner and
      reduced methylation in the Treg-specific demethylated region (TSDR) in the FOXP3
      gene. The analysis of cytokine production revealed that CD4+CD25- T cells with 5
      Aza treatment produced comparable levels of interferon (IFN)-gamma and
      transforming growth factor (TGF)-beta, but less IL-10 and more IL-2, when
      compared to cells without 5-Aza treatment. The increased IL-2 was indispensible
      to the enhanced FOXP3 expression in 5-Aza-treated CD4+CD25h cells. Finally, 5-Aza
      treated CD4+CD25h T cells could be expanded with IL-2 supplementation alone and
      maintained FOXP3 expression and suppressor function through the expansion. Our
      findings demonstrate that DNA demethylation can enhance the induction of human
      Treg cells and promise to solve one of the challenges with using Treg cells in
      therapeutic approaches.

PMID- 27877175
TI  - Thymocytes in Lyve1-CRE/S1pr1f/f Mice Accumulate in the Thymus due to Cell
      Intrinsic Loss of Sphingosine-1-Phosphate Receptor Expression.
AB  - T cell emigration from the thymus is essential for immunological homeostasis.
      While stromal cell-produced sphingosine-1-phosphate (S1P) has been shown to
      promote thymocyte egress via the S1P receptor, S1PR1, the significance of
      S1P/S1PR1 signaling in the thymic stromal cells that surround T cells remains
      unclear. To address this issue, we developed conditional knockout mice (Lyve1
      CRE/S1pr1f/f mice) in which S1pr1 was selectively targeted in cells expressing
      the lymphatic endothelial cell marker, Lyve1. In these mice, T cells were
      significantly reduced in secondary lymphoid tissues, and CD62L+ mature CD4 and
      CD8 single-positive (SP) T cells accumulated in the medulla failed to undergo
      thymus egress. Using a Lyve1 reporter strain in which Lyve1 lineage cells
      expressed tdTomato fluorescent protein, we unexpectedly found that a considerable
      proportion of the thymocytes were fluorescently labeled, indicating that they
      belonged to the Lyve1 lineage. The CD4 and CD8 SP thymocytes in Lyve1
      CRE/S1pr1f/f mice exhibited an egress-competent phenotype (HSAlow, CD62Lhigh, and
      Qa-2high), but were CD69high and lacked S1PR1 expression. In addition, CD4 SP
      thymocytes from these mice were unable to migrate to the periphery after their
      intrathymic injection into wild-type (WT) mice. In contrast, WT T cells could
      migrate to the periphery in both WT and Lyve1-CRE/S1pr1f/f thymuses. These
      results demonstrated that thymocyte egress is mediated by T cell-expressed, but
      not stromal cell-expressed, S1PR1 and caution against using the Lyve1-CRE system
      for selectively gene deletion in lymphatic endothelial cells.

PMID- 27877173
TI  - Stromal Fibroblasts in Tertiary Lymphoid Structures: A Novel Target in Chronic
      Inflammation.
AB  - Tertiary lymphoid structures (TLS) are organized aggregates of lymphocytes,
      myeloid, and stromal cells that provide ectopic hubs for acquired immune
      responses. TLS share phenotypical and functional features with secondary lymphoid
      organs (SLO); however, they require persistent inflammatory signals to arise and
      are often observed at target sites of autoimmune disease, chronic infection,
      cancer, and organ transplantation. Over the past 10 years, important progress has
      been made in our understanding of the role of stromal fibroblasts in SLO
      development, organization, and function. A complex and stereotyped series of
      events regulate fibroblast differentiation from embryonic life in SLOs to
      lymphoid organ architecture observed in adults. In contrast, TLS-associated
      fibroblasts differentiate from postnatal, locally activated mesenchyme,
      predominantly in settings of inflammation and persistent antigen presentation.
      Therefore, there are critical differences in the cellular and molecular
      requirements that regulate SLO versus TLS development that ultimately impact on
      stromal and hematopoietic cell function. These differences may contribute to the
      pathogenic nature of TLS in the context of chronic inflammation and malignant
      transformation and offer a window of opportunity for therapeutic interventions in
      TLS associated pathologies.

PMID- 27877177
TI  - Comparative Transcriptomic Analyses of Differentially Expressed Genes in
      Transgenic Melatonin Biosynthesis Ovine HIOMT Gene in Switchgrass.
AB  - Melatonin serves pleiotropic functions in prompting plant growth and resistance
      to various stresses. The accurate biosynthetic pathway of melatonin remains
      elusive in plant species, while the N-acetyltransferase and O-methyltransferase
      were considered to be the last two key enzymes during its biosynthesis. To
      investigate the biosynthesis and metabolic pathway of melatonin in plants, the
      RNA-seq profile of overexpression of the ovine HIOMT was analyzed and compared
      with the previous transcriptome of transgenic oAANAT gene in switchgrass, a model
      plant for cellulosic ethanol production. A total of 946, 405, and 807
      differentially expressed unigenes were observed in AANAT vs. control, HIOMT vs.
      control, and AANAT vs. HIOMT, respectively. Two hundred and seventy-five
      upregulated and 130 downregulated unigenes were detected in transgenic oHIOMT
      line comparing with control, including the significantly upregulated (F-box/kelch
      repeat protein, zinc finger BED domain-containing protein-3) genes, which were
      potentially correlated with enhanced phenotypes of shoot, stem and root growth in
      transgenic oHIOMT switchgrass. Several stress resistant related genes (SPX domain
      containing membrane protein, copper transporter 1, late blight resistance protein
      homolog R1A-6 OS etc.) were specifically and significantly upregulated in
      transgenic oHIOMT only, while metabolism-related genes (phenylalanine-4
      hydroxylase, tyrosine decarboxylase 1, protein disulfide-isomerase and galactinol
      synthase 2 etc.) were significantly upregulated in transgenic oAANAT only. These
      results provide new sights into the biosynthetic and physiological functional
      networks of melatonin in plants.

PMID- 27877176
TI  - The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes
      Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic
      Ribosomal Protein S6.
AB  - Protein translation is an energy consuming process that has to be fine-tuned at
      both the cell and organism levels to match the availability of resources. The
      target of rapamycin kinase (TOR) is a key regulator of a large range of
      biological processes in response to environmental cues. In this study, we have
      investigated the effects of TOR inactivation on the expression and regulation of
      Arabidopsis ribosomal proteins at different levels of analysis, namely from
      transcriptomic to phosphoproteomic. TOR inactivation resulted in a coordinated
      down-regulation of the transcription and translation of nuclear-encoded mRNAs
      coding for plastidic ribosomal proteins, which could explain the chlorotic
      phenotype of the TOR silenced plants. We have identified in the 5' untranslated
      regions (UTRs) of this set of genes a conserved sequence related to the 5'
      terminal oligopyrimidine motif, which is known to confer translational regulation
      by the TOR kinase in other eukaryotes. Furthermore, the phosphoproteomic analysis
      of the ribosomal fraction following TOR inactivation revealed a lower
      phosphorylation of the conserved Ser240 residue in the C-terminal region of the
      40S ribosomal protein S6 (RPS6). These results were confirmed by Western blot
      analysis using an antibody that specifically recognizes phosphorylated Ser240 in
      RPS6. Finally, this antibody was used to follow TOR activity in plants. Our
      results thus uncover a multi-level regulation of plant ribosomal genes and
      proteins by the TOR kinase.

PMID- 27877178
TI  - An S-adenosyl Methionine Synthetase (SAMS) Gene from Andropogon virginicus L.
      Confers Aluminum Stress Tolerance and Facilitates Epigenetic Gene Regulation in
      Arabidopsis thaliana.
AB  - Candidate clones which conferred Al tolerance to yeast transformants (TFs) were
      obtained from a cDNA library derived from a highly Al-tolerant poaceae,
      Andropogon virginicus L. One such clone, AL3A-4, encoded an S-adenosyl methionine
      synthetase (SAMS) gene. A full-length cDNA was obtained by 5'-RACE, designated
      AvSAMS1, and introduced into Arabidopsis thaliana to investigate its biological
      functions under Al stress. Two TF plant lines both showed higher tolerance than
      the Col-0 ecotype (non-TF) not only for Al stress, but also for Cu, Pb, Zn and
      diamide stresses, suggesting the AvSAMS1 was a multiple tolerance gene. More than
      40 of A. thaliana Al response-genes (Al induced genes and Al repressed genes)
      were selected from microarray results and then used for investigations of DNA or
      histone methylation status under Al stress in Col-0 and the AvSAMS1 TF line. The
      results indicated that Al stress caused alterations of methylation status in both
      DNA and histone H3 (H3K4me3 and H3K9me3) and that these alterations were
      different between the AvSAMS1 TF and Col-0, suggesting the differences were
      AvSAMS1-gene dependent. These results suggested the existence of AvSAMS1-related
      epigenetic gene-regulation under Al stress.

PMID- 27877179
TI  - Genome-Wide Identification of MicroRNAs and Their Targets in the Leaves and
      Fruits of Eucommia ulmoides Using High-Throughput Sequencing.
AB  - MicroRNAs (miRNAs), a group of endogenous small non-coding RNAs, play important
      roles in plant growth, development, and stress response processes. Eucommia
      ulmoides Oliver (hardy rubber tree) is one of the few woody plants capable of
      producing trans-1, 4-polyisoprene (TPI), also known as Eu-rubber, which has been
      utilized as an industrial raw material and is extensively cultivated in China.
      However, the mechanism of TPI biosynthesis has not been identified in E.
      ulmoides. To characterize small RNAs and their targets with potential biological
      roles involved in the TPI biosynthesis in E. ulmoides, in the present study,
      eight small RNA libraries were constructed and sequenced from young and mature
      leaves and fruits of E. ulmoides. Further analysis identified 34 conserved miRNAs
      belonging to 20 families (two unclassified families), and 115 novel miRNAs seemed
      to be specific to E. ulmoides. Among these miRNAs, fourteen conserved miRNAs and
      49 novel miRNAs were significantly differentially expressed and identified as Eu
      rubber accumulation related miRNAs. Based on the E. ulmoides genomic data, 202
      and 306 potential target genes were predicted for 33 conserved and 92 novel
      miRNAs, respectively; the predicted targets are mostly transcription factors and
      functional genes, which were enriched in metabolic pathways and biosynthesis of
      secondary metabolites. Noticeably, based on the expression patterns of miRNAs and
      their target genes in combination with the Eu-rubber accumulation, the negative
      correlation of expression of six miRNAs (Eu-miR14, Eu-miR91, miR162a, miR166a,
      miR172c, and miR396a) and their predicted targets serving as potential regulators
      in Eu-rubber accumulation. This study is the first to detect conserved and novel
      miRNAs and their potential targets in E. ulmoides and identify several candidate
      genes potentially controlling rubber accumulation, and thus provide molecular
      evidence for understanding the roles of miRNAs in regulating the TPI biosynthesis
      in E. ulmoides.

PMID- 27877180
TI  - Heat Stress Is More Damaging to Superior Spikelets than Inferiors of Rice (Oryza
      sativa L.) due to Their Different Organ Temperatures.
AB  - In general, the fertility and kernel weight of inferior spikelets of rice (Oryza
      Sativa L.) are obviously lower than those of superior spikelets, especially under
      abiotic stress. However, different responses to heat stress are seemed to show
      between the superior and inferior spikelet, and this response is scarcely
      documented that the intrinsic factors remain elusive. In order to reveal the
      mechanism underlying, two rice plants with different heat tolerance were
      subjected to heat stress of 40 degrees C at anthesis. The results indicated that
      a greater decrease in fertility and kernel weight was observed in superior
      spikelets compared to inferior spikelets. This decrease was primarily ascribed to
      their different organ temperatures, in which the temperature of the superior
      spikelets was significantly higher than that of inferior spikelets. We inferred
      the differences in canopy temperature, light intensity and panicle types, were
      the primary reasons for the temperature difference between superior and inferior
      spikelets. Under heat stress, the fertility and kernel weight of superior and
      inferior spikelets decreased as the panicle numbers per plant were reduced, which
      was accompanied by significantly increasing the canopy temperatures. Thus, it was
      suggested that the rice plant with characteristic features of an upright growth
      habit and loose panicles might be more susceptible to heat stress resulting from
      their higher canopy and spikelets temperatures.

PMID- 27877181
TI  - Plant Metabolic Engineering Strategies for the Production of Pharmaceutical
      Terpenoids.
AB  - Pharmaceutical terpenoids belong to the most diverse class of natural products.
      They have significant curative effects on a variety of diseases, such as cancer,
      cardiovascular diseases, malaria and Alzheimer's disease. Nowadays, elicitors,
      including biotic and abiotic elicitors, are often used to activate the pathway of
      secondary metabolism and enhance the production of target terpenoids. Based on
      Agrobacterium-mediated genetic transformation, several plant metabolic
      engineering strategies hold great promise to regulate the biosynthesis of
      pharmaceutical terpenoids. Overexpressing terpenoids biosynthesis pathway genes
      in homologous and ectopic plants is an effective strategy to enhance the yield of
      pharmaceutical terpenoids. Another strategy is to suppress the expression of
      competitive metabolic pathways. In addition, global regulation which includes
      regulating the relative transcription factors, endogenous phytohormones and
      primary metabolism could also markedly increase their yield. All these strategies
      offer great opportunities to enhance the supply of scarce terpenoids drugs,
      reduce the price of expensive drugs and improve people's standards of living.

PMID- 27877182
TI  - Insights from the Cold Transcriptome and Metabolome of Dendrobium officinale:
      Global Reprogramming of Metabolic and Gene Regulation Networks during Cold
      Acclimation.
AB  - Plant cold acclimation (CA) is a genetically complex phenomenon involving gene
      regulation and expression. Little is known about the cascading pattern of gene
      regulatroy network and the link between genes and metabolites during CA.
      Dendrobium officinale (DOKM) is an important medicinal and ornamental plant and
      hypersensitive to low temperature. Here, we used the large scale metabolomic and
      transcriptomic technologies to reveal the response to CA in DOKM seedlings based
      on the physiological profile analyses. Lowering temperature from 4 to -2 degrees
      C resulted in significant increase (P < 0.01) in antioxidant activities and
      electrolyte leakage (EL) during 24 h. The fitness CA piont of 0 degrees C and
      control (20 degrees C) during 20 h were firstly obtained according to
      physiological analyses. Subsequently, massive transcriptome and metabolome
      reprogramming occurred during CA. The gene to metabolite network demonstrated
      that the CA associated processes are highly energy demanding through activating
      hydrolysis of sugars, amino acids catabolism and citrate cycle. The expression
      levels of 2,767 genes were significantly affected by CA, including 153-fold
      upregulation of CBF transcription factor, 56-fold upregulation of MAPKKK16
      protein kinase. Moreover, the gene interaction and regulation network analysis
      revealed that the CA as an active process, was regulated at the transcriptional,
      post-transcriptional, translational and post-translational levels. Our findings
      highligted a comprehensive regulatory mechanism including cold signal
      transduction, transcriptional regulation, and gene expression, which contributes
      a deeper understanding of the highly complex regulatory program during CA in
      DOKM. Some marker genes identified in DOKM seedlings will allow us to understand
      the role of each individual during CA by further functional analyses.

PMID- 27877183
TI  - Time-Resolved Investigation of Molecular Components Involved in the Induction of
      [Formula: see text] High Affinity Transport System in Maize Roots.
AB  - The induction, i.e., the rapid increase of nitrate ([Formula: see text]) uptake
      following the exposure of roots to the anion, was studied integrating
      physiological and molecular levels in maize roots. Responses to [Formula: see
      text] treatment were characterized in terms of changes in [Formula: see text]
      uptake rate and plasma membrane (PM) H+-ATPase activity and related to
      transcriptional and protein profiles of NRT2, NRT3, and PM H+-ATPase gene
      families. The behavior of transcripts and proteins of ZmNRT2s and ZmNRT3s
      suggested that the regulation of the activity of inducible high-affinity
      transport system (iHATS) is mainly based on the transcriptional/translational
      modulation of the accessory protein ZmNRT3.1A. Furthermore, ZmNRT2.1 and
      ZmNRT3.1A appear to be associated in a ~150 kDa oligomer. The expression trend
      during the induction of the 11 identified PM H+-ATPase transcripts indicates that
      those mainly involved in the response to [Formula: see text] treatment are ZmHA2
      and ZmHA4. Yet, partial correlation between the gene expression, protein levels
      and enzyme activity suggests an involvement of post-transcriptional and post
      translational mechanisms of regulation. A non-denaturing Deriphat-PAGE approach
      allowed demonstrating for the first time that PM H+-ATPase can occur in vivo as
      hexameric complex together with the already described monomeric and dimeric
      forms.

PMID- 27877184
TI  - Compromised Photosynthetic Electron Flow and H2O2 Generation Correlate with
      Genotype-Specific Stomatal Dysfunctions during Resistance against Powdery Mildew
      in Oats.
AB  - Stomatal dysfunction known as "locking" has been linked to the elicitation of a
      hypersensitive response (HR) following attack of fungal pathogens in cereals. We
      here assess how spatial and temporal patterns of different resistance mechanisms,
      such as HR and penetration resistance influence stomatal and photosynthetic
      parameters in oat (Avena sativa) and the possible involvement of hydrogen
      peroxide (H2O2) in the dysfunctions observed. Four oat cultivars with
      differential resistance responses (i.e., penetration resistance, early and late
      HR) to powdery mildew (Blumeria graminis f. sp. avenae, Bga) were used. Results
      demonstrated that stomatal dysfunctions were genotype but not response-type
      dependent since genotypes with similar resistance responses when assessed
      histologically showed very different locking patterns. Maximum quantum yield
      (Fv/Fm) of photosystem II were compromised in most Bga-oat interactions and
      photoinhibition increased. However, the extent of the photosynthetic alterations
      was not directly related to the extent of HR. H2O2 generation is triggered during
      the execution of resistance responses and can influence stomatal function.
      Artificially increasing H2O2 by exposing plants to increased light intensity
      further reduced Fv/Fm ratios and augmented the patterns of stomatal dysfunctions
      previously observed. The latter results suggest that the observed dysfunctions
      and hence a cost of resistance may be linked with oxidative stress occurring
      during defense induced photosynthetic disruption.

PMID- 27877186
TI  - Selection of Reference Genes for RT-qPCR Analysis in Coccinella septempunctata to
      Assess Un-intended Effects of RNAi Transgenic Plants.
AB  - The development of genetically engineered plants that employ RNA interference
      (RNAi) to suppress invertebrate pests opens up new avenues for insect control.
      While this biotechnology shows tremendous promise, the potential for both non
      target and off-target impacts, which likely manifest via altered mRNA expression
      in the exposed organisms, remains a major concern. One powerful tool for the
      analysis of these un-intended effects is reverse transcriptase-quantitative
      polymerase chain reaction, a technique for quantifying gene expression using a
      suite of reference genes for normalization. The seven-spotted ladybeetle
      Coccinella septempunctata, a commonly used predator in both classical and
      augmentative biological controls, is a model surrogate species used in the
      environmental risk assessment (ERA) of plant incorporated protectants (PIPs).
      Here, we assessed the suitability of eight reference gene candidates for the
      normalization and analysis of C. septempunctata v-ATPase A gene expression under
      both biotic and abiotic conditions. Five computational tools with distinct
      algorisms, geNorm, Normfinder, BestKeeper, the DeltaCt method, and RefFinder,
      were used to evaluate the stability of these candidates. As a result, unique sets
      of reference genes were recommended, respectively, for experiments involving
      different developmental stages, tissues, and ingested dsRNAs. By providing a
      foundation for standardized RT-qPCR analysis in C. septempunctata, our work
      improves the accuracy and replicability of the ERA of PIPs involving RNAi
      transgenic plants.

PMID- 27877185
TI  - Lead Phytochemicals for Anticancer Drug Development.
AB  - Cancer is a serious concern at present. A large number of patients die each year
      due to cancer illnesses in spite of several interventions available. Development
      of an effective and side effects lacking anticancer therapy is the trending
      research direction in healthcare pharmacy. Chemical entities present in plants
      proved to be very potential in this regard. Bioactive phytochemicals are
      preferential as they pretend differentially on cancer cells only, without
      altering normal cells. Carcinogenesis is a complex process and includes multiple
      signaling events. Phytochemicals are pleiotropic in their function and target
      these events in multiple manners; hence they are most suitable candidate for
      anticancer drug development. Efforts are in progress to develop lead candidates
      from phytochemicals those can block or retard the growth of cancer without any
      side effect. Several phytochemicals manifest anticancer function in vitro and in
      vivo. This article deals with these lead phytomolecules with their action
      mechanisms on nuclear and cellular factors involved in carcinogenesis.
      Additionally, druggability parameters and clinical development of anticancer
      phytomolecules have also been discussed.

PMID- 27877187
TI  - Engineering Plant Immunity: Using CRISPR/Cas9 to Generate Virus Resistance.
AB  - Plant viruses infect many economically important crops, including wheat, cotton,
      maize, cassava, and other vegetables. These viruses pose a serious threat to
      agriculture worldwide, as decreases in cropland area per capita may cause
      production to fall short of that required to feed the increasing world
      population. Under these circumstances, conventional strategies can fail to
      control rapidly evolving and emerging plant viruses. Genome-engineering
      strategies have recently emerged as promising tools to introduce desirable traits
      in many eukaryotic species, including plants. Among these genome engineering
      technologies, the CRISPR (clustered regularly interspaced palindromic
      repeats)/CRISPR-associated 9 (CRISPR/Cas9) system has received special interest
      because of its simplicity, efficiency, and reproducibility. Recent studies have
      used CRISPR/Cas9 to engineer virus resistance in plants, either by directly
      targeting and cleaving the viral genome, or by modifying the host plant genome to
      introduce viral immunity. Here, we briefly describe the biology of the
      CRISPR/Cas9 system and plant viruses, and how different genome engineering
      technologies have been used to target these viruses. We further describe the main
      findings from recent studies of CRISPR/Cas9-mediated viral interference and
      discuss how these findings can be applied to improve global agriculture. We
      conclude by pinpointing the gaps in our knowledge and the outstanding questions
      regarding CRISPR/Cas9-mediated viral immunity.

PMID- 27877188
TI  - Identification of Genomic Associations for Adult Plant Resistance in the
      Background of Popular South Asian Wheat Cultivar, PBW343.
AB  - Rusts, a fungal disease as old as its host plant wheat, has caused havoc for over
      8000 years. As the rust pathogens can evolve into new virulent races which
      quickly defeat the resistance that primarily rely on race specificity, adult
      plant resistance (APR) has often been found to be race non-specific and hence is
      considered to be a more reliable and durable strategy to combat this malady. Over
      decades sets of donor lines have been identified at International Maize and Wheat
      Improvement Center (CIMMYT) representing a wide range of APR sources in wheat. In
      this study, using nine donors and a common parent "PBW343," a popular Green
      Revolution variety at CIMMYT, the nested association mapping (NAM) population of
      1122 lines was constructed to understand the APR genetics underlying these
      founder lines. Thirty-four QTL were associated with APR to rusts, and 20 of 34
      QTL had pleiotropic effects on SR, YR and LR resistance. Three chromosomal
      regions, associated with known APR genes (Sr58/Yr29/Lr46, Sr2/Yr30/Lr27, and
      Sr57/Yr18/Lr34), were also identified, and 13 previously reported QTL regions
      were validated. Of the 18 QTL first detected in this study, 7 were pleiotropic
      QTL, distributing on chromosomes 3A, 3B, 6B, 3D, and 6D. The present
      investigation revealed the genetic relationship of historical APR donor lines,
      the novel knowledge on APR, as well as the new analytical methodologies to
      facilitate the applications of NAM design in crop genetics. Results shown in this
      study will aid the parental selection for hybridization in wheat breeding, and
      envision the future rust management breeding for addressing potential threat to
      wheat production and food security.

PMID- 27877189
TI  - Genome-Wide Differences in DNA Methylation Changes in Two Contrasting Rice
      Genotypes in Response to Drought Conditions.
AB  - Differences in drought stress tolerance within diverse rice genotypes have been
      attributed to genetic diversity and epigenetic alterations. DNA methylation is an
      important epigenetic modification that influences diverse biological processes,
      but its effects on rice drought stress tolerance are poorly understood. In this
      study, methylated DNA immunoprecipitation sequencing and an Affymetrix GeneChip
      rice genome array were used to profile the DNA methylation patterns and
      transcriptomes of the drought-tolerant introgression line DK151 and its drought
      sensitive recurrent parent IR64 under drought and control conditions. The
      introgression of donor genomic DNA induced genome-wide DNA methylation changes in
      DK151 plants. A total of 1190 differentially methylated regions (DMRs) were
      detected between the two genotypes under normal growth conditions, and the DMR
      associated genes in DK151 plants were mainly related to stress response,
      programmed cell death, and nutrient reservoir activity, which are implicated to
      constitutive drought stress tolerance. A comparison of the DNA methylation
      changes in the two genotypes under drought conditions indicated that DK151 plants
      have a more stable methylome, with only 92 drought-induced DMRs, than IR64 plants
      with 506 DMRs. Gene ontology analyses of the DMR-associated genes in drought
      stressed plants revealed that changes to the DNA methylation status of genotype
      specific genes are associated with the epigenetic regulation of drought stress
      responses. Transcriptome analysis further helped to identify a set of 12 and 23
      DMR-associated genes that were differentially expressed in DK151 and IR64,
      respectively, under drought stress compared with respective controls. Correlation
      analysis indicated that DNA methylation has various effects on gene expression,
      implying that it affects gene expression directly or indirectly through diverse
      regulatory pathways. Our results indicate that drought-induced alterations to DNA
      methylation may influence an epigenetic mechanism that regulates the expression
      of unique genes responsible for drought stress tolerance.

PMID- 27877191
TI  - Corrigendum: High atomic weight, high-energy radiation (HZE) induces
      transcriptional responses shared with conventional stresses in addition to a core
      "DSB" response specific to clastogenic treatments.
AB  - [This corrects the article on p. 364 in vol. 5, PMID: 25136344.].

PMID- 27877190
TI  - Insights into the Sesquiterpenoid Pathway by Metabolic Profiling and De novo
      Transcriptome Assembly of Stem-Chicory (Cichorium intybus Cultigroup
      "Catalogna").
AB  - Stem-chicory of the "Catalogna" group is a vegetable consumed for bitter-flavored
      stems. Type and levels of bitter sesquiterpene lactones (STLs) participate in
      conferring bitterness in vegetables. The content of lactucin-and lactucopocrin
      like STLs was higher in "Molfettese" than "Galatina" landrace stalks, regardless
      of the cultivation sites, consistently with bitterness scores and gustative
      differences. The "Galatina" transcriptome assembly resulted in 58,872 unigenes,
      77% of which were annotated, paving the way to molecular investigation of the STL
      pathway. Comparative transcriptome analysis allowed the identification of 69,352
      SNPs and of 1640 differentially expressed genes that maintained the pattern
      independently of the site. Enrichment analyses revealed that 4 out of 29 unigenes
      were up-regulated in "Molfettese" vs "Galatina" within the sesquiterpenoid
      pathway. The expression of two germacrene A -synthase (GAS) and one -oxidase
      (GAO) genes of the costunolide branch correlated positively with the contents of
      lactucin-like molecules, supporting that STL biosynthesis regulation occurs at
      the transcriptional level. Finally, 46 genes encoding transcription factors (TFs)
      maintained a differential expression pattern between the two varieties regardless
      of the growth site; correlation analyses among TFs, GAS, GAO gene expressions and
      STLs contents suggest that one MYB and one bHLH may act in the pathway.

PMID- 27877192
TI  - Pure and Confounded Effects of Causal SNPs on Longevity: Insights for Proper
      Interpretation of Research Findings in GWAS of Populations with Different Genetic
      Structures.
AB  - This paper shows that the effects of causal SNPs on lifespan, estimated through
      GWAS, may be confounded and the genetic structure of the study population may be
      responsible for this effect. Simulation experiments show that levels of linkage
      disequilibrium (LD) and other parameters of the population structure describing
      connections between two causal SNPs may substantially influence separate
      estimates of the effect of the causal SNPs on lifespan. This study suggests that
      differences in LD levels between two causal SNP loci within two study populations
      may contribute to the failure to replicate previous GWAS findings. The results of
      this paper also show that successful replication of the results of genetic
      association studies does not necessarily guarantee proper interpretation of the
      effect of a causal SNP on lifespan.

PMID- 27877193
TI  - A Combined Linkage and Exome Sequencing Analysis for Electrocardiogram Parameters
      in the Erasmus Rucphen Family Study.
AB  - Electrocardiogram (ECG) measurements play a key role in the diagnosis and
      prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such
      as the PR, QRS, and QT intervals, are known to be heritable and genome-wide
      association studies of these phenotypes have been successful in identifying
      common variants; however, a large proportion of the genetic variability of these
      traits remains to be elucidated. The aim of this study was to discover loci
      potentially harboring rare variants utilizing variance component linkage analysis
      in 1547 individuals from a large family-based study, the Erasmus Rucphen Family
      Study (ERF). Linked regions were further explored using exome sequencing. Five
      suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63;
      2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR
      interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence
      data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2
      gene associated with QT (rs74608430; P = 2.8 * 10-4, minor allele frequency =
      0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the
      trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that
      the gene is involved in cytosolic Ca2+ levels (P = 3.3 * 10-3) and AMPK
      stimulated fatty acid oxidation in muscle (P = 4.1 * 10-3). Look-ups in
      bioinformatics resources showed that expression of FCRL2 is associated with
      ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam
      study. Combining the bioinformatics information with the association and linkage
      analyses, FCRL2 emerges as a strong candidate gene for QT interval.

PMID- 27877194
TI  - Adjuvant high dose rate brachytherapy for soft tissue sarcomas: initial
      experience report.
AB  - PURPOSE: Adjuvant high-dose-rate brachytherapy (HDRBT) offers advantages over low
      dose rate brachytherapy (LDRBT), although there are little data on local tumor
      control and treatment related toxicity. We report outcome in patients with
      primary, recurrent, and metastatic extremity and superficial trunk soft tissue
      sarcoma. MATERIAL AND METHODS: Eleven patients (12 sites) with intermediate or
      high grade sarcoma were treated with adjuvant HDRBT following surgical resection.
      Patients were treated at 3.4 Gy fractions delivered twice daily to a total dose
      of 34 Gy (1 patient received 9 fractions). RESULTS: With median follow-up of 20.8
      months, 1 patient developed a local recurrence. 2-year local control and overall
      survival are 89% and 71%, respectively. Wound complications occurred in 3 sites.
      Two of the wound complications developed in the area of previous external beam
      radiotherapy (EBRT). CONCLUSION: Surgical resection followed by HDRBT is
      associated with excellent early local tumor control and acceptable wound
      complication.

PMID- 27877195
TI  - Pulsed dose rate brachytherapy as the boost in combination with external beam
      irradiation in base of tongue cancer. Long-term results from a uniform clinical
      series.
AB  - PURPOSE: To evaluate long time outcome with regard to local tumour control, side
      effects and quality of life of combined pulsed dose rate (PDR) boost and
      hyperfractionated accelerated external beam radiotherapy (EBRT) for primary base
      of tongue (BOT) cancers. MATERIAL AND METHODS: Between 1994 and 2007, the number
      of 83 patients were treated with primary T1-T4 BOT cancers. Seven patients (8%)
      were T1-2N0 (AJCC stage I-II) and 76 (92%) patients were T1-2N+ or T3-4N0-2 (AJCC
      stage III-IV). The mean estimated primary tumour volume was 15.4 (1-75) cm3. EBRT
      was given with 1.7 Gy bid to 40.8 Gy to primary tumour and bilateral neck lymph
      nodes in 2.5 weeks. PDR boost of 35 Gy and a neck dissection in clinical node
      positive case was performed 2-3 weeks later. The patients were followed for a
      median of 54 (2-168) months. RESULTS: The 2-, 5- and 10-years rates of actuarial
      local control were 91%, 89% and 85%, overall survival 85%, 65% and 44%, disease
      free survival 86%, 80% and 76%, respectively. The regional control rate was 95%.
      Six patients (7%) developed distant metastases. A dosimetric analysis showed a
      mean of 100% isodose volume of 58.2 (16.7-134) cm3. In a review of late
      complications 11 cases of minor (13%) and 5 of major soft tissue necroses (6%),
      as well as 6 cases of osteoradionecroses (7%) were found. The patients median
      subjective SOMA/LENT scoring at last follow up was as follow: grade 0 for pain
      and trismus, grade 1 for dysphagia and taste alteration, and grade 2 for
      xerostomia. Global visual-analogue-scale (VAS) scoring of quality of life was 8.
      CONCLUSION: Local and regional tumour control rate was excellent in this
      treatment protocol. The data shows the PDR boost as at least as effective as
      published continuous low dose rate (CLDR) results.

PMID- 27877196
TI  - Prophylactic urethral stenting with Memokath(r) 028SW in prostate cancer patients
      undergoing prostate 125I seed implants: phase I/II study.
AB  - PURPOSE: To study the feasibility/toxicity of urethral stenting with the
      Memokath(r) 028SW stent in patients undergoing prostate implant (PI) for prostate
      adenocarcinoma. MATERIAL AND METHODS: An Investigational Device Exemption from
      the Food and Drug Administration (FDA) and institutional review board (IRB)
      approval were obtained. Twenty patients enrolled. Baseline American Urological
      Association (AUA) score was obtained prior to PI. Follow-up information was
      obtained with weekly phone calls for the first 12 weeks and biweekly calls for
      the next 12 weeks to assess toxicity and AUA score. Removal of the stent was
      planned at six months after PI, or earlier due to excessive toxicity/patient
      request. RESULTS: Median age was 66.5 years. The median prostate volume was 39 cc
      (range: 10-90). The median baseline AUA score was 7.5 (range: 1-21). Three
      patients required intermittent self-catheterization (ISC) within 3 days after PI.
      No patients required ISC beyond day 3 after PI. The median duration of ISC was 1
      day (range: 1-2). AUA scores returned to baseline values 6 weeks after PI. The
      week 6 AUA score was 10 (range: 4-16). Seven patients (35%) underwent early
      removal because of patient preference. The reasons were: incontinence (n = 3),
      discomfort (n = 2), hematuria (n = 1), and obstructive symptoms (n = 1). The
      median time of stent removal in these patients was 13.9 weeks (range: 0.9-21.4).
      Thirteen patients (65%) had ISC and/or urinary catheterization post stent
      removal. Median time for ISC use was 10 days (range: 1-90). CONCLUSIONS: Urethral
      stenting with Memokath(r) in patients undergoing PI was feasible, but resulted in
      relatively high rate of urinary incontinence and discomfort. Given the adverse
      effects experienced by patients of this study, further studies should focus only
      on patients with highest risk of urinary obstruction from PI or those with
      obstruction needing ISC.

PMID- 27877197
TI  - Evaluation of variation in dose of organs at risk in intracavitary brachytherapy
      of cervical cancer - a prospective study.
AB  - PURPOSE: The aim of this work was to evaluate the variation of dose in organs at
      risk (OARs) in fractionated high dose rate intracavitary brachytherapy (HDR-BT)
      for cervical cancer. MATERIAL AND METHODS: A prospective study was carried out on
      20 cervical cancer patients treated with fractionated (HDR-BT). International
      Commission on Radiation Units and Measurement (ICRU) bladder (bICRU) and rectum
      (rICRU) points were defined according to ICRU Report 38, using two orthogonal
      radiograph images taken by Simulator (Simulix HQ(r)) and prospectively kept to
      less than 80% of prescription dose to point A during real treatment planning
      process using the Plato Sunrise Treatment Planning System(r). RESULTS: The
      average variation of individuals in estimated doses of OARs in the inter
      fractional as well as in a single fraction were 2.4% and 0.7% of point A for
      rICRU, 4.3% and 1.6% for bICRU, and 0.8% & 0.2% for point B, whereas point A
      itself was found to be 1.6% & 0.6%. CONCLUSIONS: Average variation of the
      delivery of dose per fraction was found well within the recommended limit. The
      study observed smaller variation of doses to OARs which could present better
      reproducibility of geometry of (HDR-BT) applicators and its relative displacement
      with critical structures. Transportation of patient from simulator room to
      treatment room causes small uncertainties in delivery dose.

PMID- 27877198
TI  - Dosimetric evaluation of internal shielding in a high dose rate skin applicator.
AB  - PURPOSE: The Valencia HDR applicators are accessories of the microSelectron HDR
      afterloading system (Nucletron) shaped as truncated cones. The base of the cone
      is either 2 or 3 cm diameter. They are intended to treat skin lesions, being the
      typical prescription depth 3 mm. In patients with eyelid lesions, an internal
      shielding is very useful to reduce the dose to the ocular globe. The purpose of
      this work was to evaluate the dose enhancement from potential backscatter and
      electron contamination due to the shielding. MATERIAL AND METHODS: Two methods
      were used: a) Monte Carlo simulation, performed with the GEANT4 code, 2 cm
      Valencia applicator was placed on the surface of a water phantom in which 2 mm
      lead slab was located at 3 mm depth; b) radiochromic EBT films, used to verify
      the Monte Carlo results, positioning the films at 1.5, 3, 5 and 7 mm depth,
      inside the phantom. Two irradiations, with and without the lead shielding slab,
      were carried out. RESULTS: The Monte Carlo results showed that due to the
      backscatter component from the lead, the dose level raised to about 200% with a
      depth range of 0.5 mm. Under the lead the dose level was enhanced to about 130%
      with a depth range of 1 mm. Two millimeters of lead reduce the dose under the
      slab with about 60%. These results agree with film measurements within
      uncertainties. CONCLUSIONS: In conclusion, the use of 2 mm internal lead
      shielding in eyelid skin treatments with the Valencia applicators were evaluated
      using MC methods and EBT film dosimetry. The minimum bolus thickness that was
      needed above and below the shielding was 0.5 mm and 1 mm respectively, and the
      shielding reduced the absorbed dose delivered to the ocular globe by about 60%.

PMID- 27877199
TI  - Revision of the dosimetric parameters of the CSM11 LDR Cs-137 source.
AB  - PURPOSE: The clinical use of brachytherapy sources requires the existence of
      dosimetric data with enough of quality for the proper application of treatments
      in clinical practice. It has been found that the published data for the low dose
      rate CSM11 Cs-137 source lacks of smoothness in some regions because the data are
      too noisy. The purpose of this study was to calculate the dosimetric data for
      this source in order to provide quality dosimetric improvement of the existing
      dosimetric data of Ballester et al. [1]. MATERIAL AND METHODS: In order to obtain
      the dose rate distributions Monte Carlo simulations were done using the GEANT4
      code. A spherical phantom 40 cm in radius with the Cs-137 source located at the
      centre of the phantom was used. RESULTS: The results from Monte Carlo simulations
      were applied to derive AAPM Task Group 43 dosimetric parameters: anisotropy
      function, radial dose function, air kerma strength and dose rate constant. The
      dose rate constant obtained was 1.094 +/- 0.002 cGy h-1 U-1. The new calculated
      data agrees within experimental uncertainties with the existing data of Ballester
      et al. but without the statistical noise of that study. CONCLUSIONS: The obtained
      data presently fulfills all the requirements of the TG-43U1 update and thus it
      can be used in clinical practice.

PMID- 27877201
TI  - Can local adaptation research in plants inform selection of native plant
      materials? An analysis of experimental methodologies.
AB  - Local adaptation is used as a criterion to select plant materials that will
      display high fitness in new environments. A large body of research has explored
      local adaptation in plants, however, to what extent findings can inform
      management decisions has not been formally evaluated. We assessed local
      adaptation literature for six key experimental methodologies that have the
      greatest effect on the application of research to selecting plant materials for
      natural resource management: experimental environment, response variables,
      maternal effects, intraspecific variation, selective agents, and spatial and
      temporal variability. We found that less than half of experiments used reciprocal
      transplants or natural field conditions, which are both informative for
      revegetation and restoration. Population growth rate was rarely (5%) assessed,
      and most studies measured only single generations (96%) and ran for less than a
      year. Emergence and establishment are limiting factors in successful revegetation
      and restoration, but the majority of studies measured later life-history stages
      (66%). Additionally, most studies included limited replication at the population
      and habitat levels and tested response to single abiotic selective factors (66%).
      Local adaptation research should be cautiously applied to management; future
      research could use alternative methodologies to allow managers to directly apply
      findings.

PMID- 27877200
TI  - Genomics advances the study of inbreeding depression in the wild.
AB  - Inbreeding depression (reduced fitness of individuals with related parents) has
      long been a major focus of ecology, evolution, and conservation biology. Despite
      decades of research, we still have a limited understanding of the strength,
      underlying genetic mechanisms, and demographic consequences of inbreeding
      depression in the wild. Studying inbreeding depression in natural populations has
      been hampered by the inability to precisely measure individual inbreeding.
      Fortunately, the rapidly increasing availability of high-throughput sequencing
      data means it is now feasible to measure the inbreeding of any individual with
      high precision. Here, we review how genomic data are advancing our understanding
      of inbreeding depression in the wild. Recent results show that individual
      inbreeding and inbreeding depression can be measured more precisely with genomic
      data than via traditional pedigree analysis. Additionally, the availability of
      genomic data has made it possible to pinpoint loci with large effects
      contributing to inbreeding depression in wild populations, although this will
      continue to be a challenging task in many study systems due to low statistical
      power. Now that reliably measuring individual inbreeding is no longer a
      limitation, a major focus of future studies should be to more accurately quantify
      effects of inbreeding depression on population growth and viability.

PMID- 27877202
TI  - Rapid genetic and ecological differentiation during the northern range expansion
      of the venomous yellow sac spider Cheiracanthium punctorium in Europe.
AB  - Although poleward range expansions are commonly attributed to global change, a
      complex interaction of ecological and evolutionary factors might contribute to
      expansion success. Here, we study the expansion of the yellow sac spider
      Cheiracanthium punctorium, a medically important species in Central Europe. Using
      microsatellite markers and DNA sequences, morphological and climate niche
      analyses, we identify factors associated with the spider's expansion success. Our
      results indicate that the species' initial expansion has been triggered by
      environmental change and preadaptation in the source populations. However,
      despite extensive gene flow, expanding populations maintain genetic and
      morphological differentiation from native ones, which is correlated with climatic
      niche differences. Moreover, expanding spiders might have temporarily escaped an
      eggsac parasite that causes high mortality in the native range. Hence, our
      results paint a complex picture of diverse factors associated with expansion
      success. We speculate that expanding populations might be capable of adapting to
      novel ecological conditions in northern Europe. This could allow a substantial
      range expansion, much farther than by environmental change alone. Our
      distribution model predicts that the spider will soon massively spread over most
      of northern Europe, bringing along considerable health concerns.

PMID- 27877203
TI  - Past and present dynamics of sorghum and pearl millet diversity in Mount Kenya
      region.
AB  - Crop populations in smallholder farming systems are shaped by the interaction of
      biological, ecological, and social processes, occurring on different
      spatiotemporal scales. Understanding these dynamics is fundamental for the
      conservation of crop genetic resources. In this study, we investigated the
      processes involved in sorghum and pearl millet diversity dynamics on Mount Kenya.
      Surveys were conducted in ten sites distributed along two elevation transects and
      occupied by six ethnolinguistic groups. Varieties of both species grown in each
      site were inventoried and characterized using SSR markers. Genetic diversity was
      analyzed using both individual- and population-based approaches. Surveys of seed
      lot sources allowed characterizing seed-mediated gene flow. Past sorghum
      diffusion dynamics were explored by comparing Mount Kenya sorghum diversity with
      that of the African continent. The absence of structure in pearl millet genetic
      diversity indicated common ancestry and/or important pollen- and seed-mediated
      gene flow. On the contrary, sorghum varietal and genetic diversity showed
      geographic patterns, pointing to different ancestry of varieties, limited pollen
      mediated gene flow, and geographic patterns in seed-mediated gene flow. Social
      and ecological processes involved in shaping seed-mediated gene flow are further
      discussed.

PMID- 27877204
TI  - Increases in the mean and variability of thermal regimes result in differential
      phenotypic responses among genotypes during early ontogenetic stages of lake
      sturgeon (Acipenser fulvescens).
AB  - Climate change is affecting thermal conditions worldwide. Understanding
      organismal responses associated with predicted changes are essential for
      predicting population persistence. Few studies have examined the effects of both
      increased mean and variance in temperature on organismal traits, particularly
      during early life stages. Using lake sturgeon (Acipenser fulvescens) from Black
      Lake, MI, we tested whether phenotypic variation differed among families reared
      in two constant (10 and 18 degrees C) and two fluctuating-temperature treatments
      (10-19 degrees C) representing temperatures experienced in the river and a
      simulated anthropogenic disturbance. Body length, body area, and yolk-sac area
      were quantified at hatch. Family-by-treatment interactions explained up to 50% of
      the variance observed among families in offspring hatch traits. Families
      incubated in 18 degrees C and the fluctuating anthropogenic treatment had 6-10
      times higher variance in traits than those incubated at 10 degrees C. Hatched
      larvae were placed in raceways with ambient river water. Emergence body length,
      emergence timing, and growth were quantified upon emergence. Families differed in
      time to emergence and growth with the greatest range observed in the 18 degrees C
      treatment. Results demonstrate that differential responses among genotypes to
      changes in the mean and variability of thermal incubation regimes can affect
      traits at hatch as well as a subsequent ontogenetic stage.

PMID- 27877206
TI  - Genomic signatures among Oncorhynchus nerka ecotypes to inform conservation and
      management of endangered Sockeye Salmon.
AB  - Conservation of life history variation is an important consideration for many
      species with trade-offs in migratory characteristics. Many salmonid species
      exhibit both resident and migratory strategies that capitalize on benefits in
      freshwater and marine environments. In this study, we investigated genomic
      signatures for migratory life history in collections of resident and anadromous
      Oncorhynchus nerka (Kokanee and Sockeye Salmon, respectively) from two lake
      systems, using ~2,600 SNPs from restriction-site-associated DNA sequencing (RAD
      seq). Differing demographic histories were evident in the two systems where one
      pair was significantly differentiated (Redfish Lake, FST = 0.091 [95% confidence
      interval: 0.087 to 0.095]) but the other pair was not (Alturas Lake, FST = -0.007
      [-0.008 to -0.006]). Outlier and association analyses identified several
      candidate markers in each population pair, but there was limited evidence for
      parallel signatures of genomic variation associated with migration. Despite lack
      of evidence for consistent markers associated with migratory life history in this
      species, candidate markers were mapped to functional genes and provide evidence
      for adaptive genetic variation within each lake system. Life history variation
      has been maintained in these nearly extirpated populations of O. nerka, and
      conservation efforts to preserve this diversity are important for long-term
      resiliency of this species.

PMID- 27877207
TI  - Sockeye salmon repatriation leads to population re-establishment and rapid
      introgression with native kokanee.
AB  - Re-establishing salmonid populations to areas historically occupied has the
      substantial potential for conservation gains; however, such interventions also
      risk negatively impacting native resident stocks. Here, we assessed the success
      of the hatchery-assisted reintroduction of anadromous sockeye salmon
      (Oncorhynchus nerka) into Skaha Lake, British Columbia, Canada, and evaluated the
      genetic consequences for native kokanee, a freshwater-obligate ecotype, using
      single nucleotide polymorphism genotypic data collected from the reference
      samples of spawning Okanagan River sockeye and Skaha Lake kokanee presockeye
      reintroduction, along with annual trawl survey and angler-caught samples obtained
      over an eight-year period. Significant differentiation was detected between
      sockeye and kokanee reference samples, with >99% stock assignment. Low
      proportions of sockeye and hybrids were detected within 2008 and 2010 age-0 trawl
      samples; however, by 2012, 28% were sockeye, rising to 41% in 2014. The number of
      hybrids detected rose proportionally with the increase in sockeye and exhibited
      an intermediate phenotype. Our results indicate that the reintroduction of
      anadromous sockeye to Skaha Lake is succeeding, with large numbers returning to
      spawn. However, hybridization with native kokanee is of concern due to the
      potential for demographic or genetic swamping, with ongoing genetic monitoring
      necessary to assess the long-term effects of introgression and to support
      interactive fisheries management.

PMID- 27877205
TI  - Spatial patterns of immunogenetic and neutral variation underscore the
      conservation value of small, isolated American badger populations.
AB  - Small and isolated populations often exhibit low genetic diversity due to drift
      and inbreeding, but may simultaneously harbour adaptive variation. We investigate
      spatial distributions of immunogenetic variation in American badger subspecies
      (Taxidea taxus), as a proxy for evaluating their evolutionary potential across
      the northern extent of the species' range. We compared genetic structure of 20
      microsatellites and the major histocompatibility complex (MHC DRB exon 2) to
      evaluate whether small, isolated populations show low adaptive polymorphism
      relative to large and well-connected populations. Our results suggest that gene
      flow plays a prominent role in shaping MHC polymorphism across large spatial
      scales, while the interplay between gene flow and selection was stronger towards
      the northern peripheries. The similarity of MHC alleles within subspecies
      relative to their neutral genetic differentiation suggests that adaptive
      divergence among subspecies can be maintained despite ongoing gene flow along
      subspecies boundaries. Neutral genetic diversity was low in small relative to
      large populations, but MHC diversity within individuals was high in small
      populations. Despite reduced neutral genetic variation, small and isolated
      populations harbour functional variation that likely contribute to the species
      evolutionary potential at the northern range. Our findings suggest that
      conservation approaches should focus on managing adaptive variation across the
      species range rather than protecting subspecies per se.

PMID- 27877208
TI  - Selection, Analysis and Improvement of Anti-Angiogenesis Compounds Identified by
      an Anti-HIF-1alpha Screening and Validation System.
AB  - Cancer cells resort to activating hypoxia-inducible factor-1 (HIF-1) as one of
      several responses to hypoxic conditions. Overexpression of HIF-1, the
      transcriptional regulator for a group of malignant-pathway related genes
      including vascular endothelial growth factor (VEGF), is associated with increased
      tumor growth, vascularization, and metastasis. HIF-1 is composed of an inducible
      subunit, HIF-1alpha and a constitutively expressed subunit, HIF-1beta. HIF-1
      activity is mainly dependent on the level of HIF-1alpha protein, the inducible
      and regulatory subunit of the HIF-1 heterodimer complex; thus, identification of
      novel anti-HIF-1alpha agents will lead to effective blockage of the HIF-1 (HIF
      1alpha)-mediated "switch-on" function for those malignant-pathway related genes
      and suppression of the HIF-1alpha/VEGF-mediated signaling pathway that promotes
      cancer progression and metastasis. While there is an extremely large number of
      small molecule compounds in the database (compound libraries), the currently
      existing screening system is inefficient and time-consuming; or, at best, the
      application of the existing screening system is very limited as it is usually not
      coupled with biological validation processes. The further development of
      potential drugs is partly hindered due to the cumbersome steps in between the
      primary screen and consequent validation: the slow, exhausted and sometimes lack
      of a linked biological validation process contributes to the dismal fate of scant
      compounds uncovered in the primary screen. To improve upon the status quo, we
      developed a prototype screening system that is coupled anti-HIF-1alpha primary
      screen with secondary anti-VEGF/anti-angiogenesis validation screens. We used
      breast cancer cells as the model to select potent anti-HIF-1alpha small-molecule
      compounds by their abilities to inhibit transactivation of a VEGF promoter fused
      to a luciferase reporter gene under hypoxia. Positive compounds were then
      validated by a series of assays that confirm compounds' anti-HIF-1alpha
      activities including measurement of their effects on HIF-1alpha downstream VEGF
      gene expression and angiogenic ability of breast cancer cells. Moreover, we
      demonstrated that we could further improve the compound's potency of anti-HIF
      1alpha and anti-angiogenesis by modifying the identified lead to synthesize a
      superior (novel) drug.

PMID- 27877209
TI  - Impact of Systemic Therapy and Recurrence Pattern on Survival Outcome after
      Radiofrequency Ablation for Colorectal Liver Metastases.
AB  - Background: Most patients undergoing radiofrequency ablation (RFA) of colorectal
      liver metastasases (CLM) develop disease recurrence, but little is known about
      the effect of recurrence patterns and/or systemic therapy on outcome. In this
      study, we examined the recurrence patterns and survival after systemic therapy
      plus RFA in patients with unresectable CLM without extrahepatic disease. The aims
      were to analyze the effect of recurrence patterns on survival and to assess the
      relative benefit contributed by systemic therapy and local ablation to disease
      control and patient outcome. Methods: From January 2002 to December 2012, 113
      patients underwent RFA of liver-limited CLM after systemic therapy. Univariate
      and multivariate analyses for associations between clinical and/or treatment
      related variables, recurrence-free survival (RFS), recurrence patterns, and
      overall survival (OS) were carried out. Results: Of 113 patients, 105 (92.8%) had
      disease recurrence (median RFS: 6.1 months). Lower post-recurrence OS was
      observed after early (<=6 months) than after late recurrence (8.5 versus 24.0
      months, p < 0.001). Recurrence sites were RFA-sites only (4.8%), liver-only
      (57.1%), lung-only (10.5%), or multiple (27.6%); the corresponding post
      recurrence OS was 21, 19, 39, and 7 months (p < 0.001), respectively. Response to
      pre-RFA systemic therapy was the strongest predictor for OS (hazard ratio [HR]
      5.28), RFS (HR 3.30), early (odds ratio [OR] 6.34) and multiple-site recurrence
      (OR 3.83) (p < 0.01), respectively; only responders achieved 5-year OS and RFS
      (29% and 12% versus 0% and 0% for non-responders, p < 0.001, respectively).
      Conclusions: Survival after RFA for liver-limited CLM is strongly linked to the
      timing and pattern of non-local disease recurrence. Local ablation efficacy is
      necessary but not sufficient to obtain long-term disease control. Effective pre
      RFA systemic therapy does favourably affect the incidence, timing and patterns of
      recurrence and long-term survival and appears essential for the tailoring of RFA
      application to maximize patient benefit.

PMID- 27877210
TI  - In vivo Antitumor Effect of an HPV-specific Promoter driving IL-12 Expression in
      an HPV 16-positive Murine Model of Cervical Cancer.
AB  - Human papillomavirus (HPV) is a DNA virus that infects epithelial cells and has
      been implicated in the development of cervical cancer. Few therapeutic strategies
      have been designed for the treatment of cervical intraepithelial neoplasia, a
      precursor of cervical cancer. In these early stages, the HPV E2 protein is the
      most important viral factor involved in viral gene expression and plays crucial
      roles during the vegetative viral cycle in epithelial cells. Papillomavirus E2
      binds specifically to palindromic ACCN6GGT sequences, referred to as the E2
      binding sites (E2BS), which are concentrated within the viral long control
      region, and which are responsible for regulation of the HPV protein's expression.
      Here, we consider E2BS as a candidate sequence to induce the expression of
      antiviral therapeutic genes selectively in HPV-infected cells expressing the E2
      protein. This study focuses on the use of an HPV-specific promoter comprised of
      four E2BS to drive the expression of IL-12, leading to an antitumor effect in an
      HPV-positive murine tumor model. The therapeutic strategy was implemented via
      viral gene therapy using adenoviral vectors with recombinant E2 and IL-12 genes
      and E2BS-IL-12. We demonstrate that the HPV-specific promoter E2BS is functional
      in vitro and in vivo through transactivation of HPV E2 transcription factor.

PMID- 27877211
TI  - The Three-Gene Signature in Urinary Extracellular Vesicles from Patients with
      Clear Cell Renal Cell Carcinoma.
AB  - Renal cell carcinoma (RCC) accounts for more than 2% of neoplasias in humans
      worldwide. Renal biopsy is the gold standard among the diagnostic procedures, but
      it is invasive and not suitable for all patients. Therefore, new reliable and non
      invasive biomarkers for RCC are required. Secretion of extracellular vesicles
      (EVs), containing RNA molecules that can be transferred between cells, appears to
      be a common feature of neoplasia. Consistently, cancer-derived EVs are increased
      in blood and urine. Therefore, urinary samples may be a non-invasive approach for
      discovering new diagnostic biomarkers. We enrolled 46 patients of whom 33 with
      clear cell renal cell carcinoma (ccRCC) and 22 healthy subjects (HS). Urinary EVs
      were isolated by differential centrifugation. Microarray analysis led to the
      identification of RNA molecules that were validated using RT-qPCR. We found that
      urinary exosomal shuttle RNA (esRNA) pattern was significantly different in ccRCC
      patients compared to HS and to non-clear cell RCC (non-ccRCC) and we identified
      three esRNAs involved in the tumor biology that may be potentially suitable as
      non-invasive gene signature. GSTA1, CEBPA and PCBD1 esRNA levels were decreased
      in urine of patients compared with HS. This pattern was specific of the ccRCC and
      one month after partial or radical nephrectomy the esRNA levels increased to
      reach the normal level. This study suggests, for the first time, the potential
      use of the RNA content of urinary EVs to provide a non-invasive first step to
      diagnose the ccRCC.

PMID- 27877213
TI  - Involvement of BAFF and APRIL in Resistance to Apoptosis of Acute Myeloid
      Leukemia.
AB  - B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing
      ligand (APRIL), two members of the tumour necrosis factor (TNF) superfamily,
      beyond playing a significant role in normal B-cell development, promote survival
      and proliferation of malignant B cells. Both ligands interact with 3 receptors:
      BAFF-R, specific to BAFF, and TACI and BCMA which are shared by both BAFF and
      APRIL. Here we wished to investigate the potential role of these proteins in
      resistance of acute myeloid leukaemia (AML) blasts to apoptosis. We found that
      the levels of both mRNA and proteins of APRIL, BAFF and their receptors were
      expressed in leukaemic cells of 24 newly diagnosed, untreated AML patients. We
      also demonstrated that patients who did not further respond to induction therapy
      (NR) presented with significantly higher baseline APRIL and BAFF expression on
      AML blasts as compared to these subjects who, after induction, achieved complete
      remission (CR) following induction therapy. Moreover, we observed striking
      differences in baseline levels of BCMA between CR and NR patients as we did not
      find detectable expression of this receptor in the latter group of patients.
      Interestingly, we found that AML blasts collected at baseline from NR patients
      cultured in presence of exogenous BAFF and APRIL were significantly more
      resistant to spontaneous or drug-induced apoptosis as compared with cells derived
      from CR patients. Altogether, our data confirm that BAFF and APRIL signaling play
      important role in AML pathogenesis and susceptibility to cytotoxic therapy while
      measuring of BCMA expression on AML cells can become a novel prognostic factor
      for chemotherapy response.

PMID- 27877212
TI  - Early Integration of Palliative Care in Oncology Practice: Results of the Italian
      Association of Medical Oncology (AIOM) Survey.
AB  - BACKGROUND: Early integration of palliative care in oncology practice
      ("simultaneous care", SC) has been shown to provide better care resulting in
      improved quality-of-life and also survival. We evaluated the opinions of Italian
      Association of Medical Oncology (AIOM) members. PATIENTS AND METHODS: A 37-item
      questionnaire was delivered to 1119 AIOM members. Main areas covered were:
      social, ethical, relational aspects of disease and communication, training,
      research, organizational and management models in SC. Three open questions
      explored the definition of Quality of Life, Medical Oncologist and Palliative
      Care. RESULTS: Four hundred and forty-nine (40.1%) medical oncologists returned
      the questionnaires. Forty-nine percent stated they address non-curability when
      giving a diagnosis of metastatic tumor, and 43% give the information only to
      patients who clearly ask for it. Fifty-five percent say the main formative
      activity in palliative medicine came from attending meetings and 90% agree that
      specific palliative care training should be part of the core curriculum in
      oncology. Twenty-two percent stated they consulted guidelines for symptom
      management, 45% relied upon personal experience and 26% make a referral to a
      palliative care specialist. Seventy-four percent were in favor of more research
      in palliative medicine. An integration between Units of Oncology and Palliative
      Care Services early in the course of advanced disease was advocated by 86%.
      Diverse and multifaceted definitions were given for the concepts of Quality of
      Life, Palliative Care and Medical Oncologist. CONCLUSION: SC is felt as an
      important task, as well as training of medical oncologists in symptom management
      and research in this field.

PMID- 27877215
TI  - The C-reactive Protein/Albumin Ratio Is an independent Prognostic Factor for
      Overall Survival in Patients with Nasopharyngeal Carcinoma Receiving Intensity
      Modulated Radiotherapy.
AB  - This study aims to investigate the prognostic value of the C-reactive
      protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the
      intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC
      treated between January 2007 and December 2012 were retrospectively reviewed.
      Serum albumin and CRP levels were measured before treatment. The associations
      between the CRP/ALB ratio and clinicopathological parameters were analyzed.
      Multivariate analyses using the Cox proportional hazards model were performed to
      identify significant prognostic factors associated with overall survival (OS).
      The prognostic value of the CRP/ALB ratio was determined using receiver operating
      characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was
      0.141. High CRP/ALB ratio was significantly associated with older age (P <
      0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024).
      Patients with an elevated CRP/ALB ratio (>= 0.141) had poorer OS than those with
      a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001).
      Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95%
      confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575;
      95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059;
      P = 0.015) were independently associated with OS. In conclusion, pretreatment
      CRP/ALB ratio is an objective biomarker with significant prognostic value for OS
      in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify
      patients and may help facilitate individualized treatment of high-risk cases.

PMID- 27877214
TI  - Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A
      Systematic Review and Meta-Analysis.
AB  - The growing interest in enhancing and spreading colorectal cancer (CRC) screening
      has been stimulating the exploration of novel biomarkers with greater sensitivity
      and specificity than immunochemical faecal occult blood test (iFOBT). The present
      study provides i) a systematic review of the urinary biomarkers that have been
      tested to achieve early CRC diagnosis and assess the risk of colorectal adenoma
      and adenocarcinoma, and ii) a meta-analysis of the data regarding the urinary
      prostaglandin (PG) metabolite PGE-M. As regard to gene markers, we found
      significantly different percent methylation of the vimentin gene in CRC patients
      and healthy controls (HC) (p<0.0001). Respect to metabolism of nitrogenous bases,
      cytidine, 1-methyladenosine, and adenosine, have higher concentrations in CRC
      patients than in HC (respectively, p<0.01, p=0.01, and p<0.01). As regard to
      spermine we found that N1,N12 diacetyl spermine (DiAcSpm) and N1, N8
      diacetylspermidine (DiAcSpd) were significantly higher in CRC than in HC
      (respectively p=0.01 and p<0.01). Respect to PGE-M, levels were higher in CRC
      than in those with multiple polyposis (p<0.006) and HC subjects (p<0.0004). PGE-M
      seems to be the most interesting and promising urinary marker for CRC and adenoma
      risk assessment and for CRC screening. In conclusion, evidence suggests that
      urinary biomarker could have a potential role as urinary biomarkers in the
      diagnosis of colorectal cancer. Particularly, PGE-M seems to be the most
      promising urinary marker for CRC early detection.

PMID- 27877216
TI  - Investigating a Correlation between Chemoradiotherapy Schedule Parameters and
      Overall Survival in a real-life LD SCLC Patient Cohort.
AB  - Background: Chemoradiotherapy (CRT) is a treatment standard in limited disease
      (LD) small cell lung cancer (SCLC). Currently, the timing of thoracic radiation
      therapy (TRT) remains the subject of randomised trials and meta-analyses. To
      investigate a correlation between CRT schedule parameters and overall survival
      (OS) in a real-life patient cohort, a temporal analysis was performed. Methods:
      182 LD SCLC patients successfully treated with definitive CRT were
      retrospectively reviewed. TRT was applied concurrently or sequentially. Impact of
      the treatment mode and interval of simultaneous treatment (IST) (an interval in
      days when chemotherapy and TRT were applied simultaneously, including time
      between chemotherapy cycles and weekends) on OS was analysed. Results: 71 (39%)
      patients were treated with concurrent and 111 (61%) with sequential CRT. Median
      overall survival (MS) for the entire cohort was 534 days (95%CI 461 - 607)
      without any significant difference between the concurrent and sequential groups
      (589: 95%CI 358 - 820 vs. 533: 95%CI 446 - 620 days, p=0.746, log-rank test). IST
      was 0 days in 111 (61%) patients treated sequentially whereas in the concurrent
      group, 20 (11%) and 51 (28%) patients showed an IST < 35 and > 35 days,
      respectively. Patients with IST > 0 and < 35 days demonstrated a trend to
      improved overall survival (MS: IST 0 vs. > 35 vs. < 35 was 533 vs. 448 vs. 1169
      days, p=0.109, log-rank test). When patients treated with sequential CRT (IST 0)
      were excluded from the analysis, statistical difference in overall survival
      according to the IST subgroups (IST > 35 vs. < 35) became significant (p=0.021,
      log-rank test). On multivariate analysis of patients treated with concurrent CRT,
      IST > 0 and < 35 days remained a variable that significantly correlated with
      better overall survival (p=0.039, HR 0.38). Conclusion: In this real-life LD SCLC
      patient cohort, improved overall survival was achieved in patients treated with
      CRT schedule according to the IST > 0 and < 35-day concept. By exceeding the 35
      day interval, we have seen deterioration in survival.

PMID- 27877217
TI  - Pregnancy Specific beta-1 Glycoprotein 1 is Expressed in Pancreatic Ductal
      Adenocarcinoma and its Subcellular Localization Correlates with Overall Survival.
AB  - Proteins of the pregnancy specific beta-1 glycoprotein (PSG) family are renowned
      for their elevated expression during pregnancy. Only few reports have
      investigated their expression in adenocarcinomas. We studied the expression of
      PSG1 in pancreatic adenocarcinoma (PDAC). In a cohort of 104 patient samples,
      immunohistochemical analysis determined PSG1 expression in every specimen. PSG1
      was found at apical and cytoplasmic localization or solely at cytoplasmic
      localization, with the latter case being correlated to shortened median survival
      (25 vs 11 months, logrank p-value < 0.001). At the same time, enzyme linked
      immunosorbent assay (ELISA) did not detect elevated PSG1 levels in the plasma of
      PDAC patients as opposed to the plasma of healthy, non-pregnant control
      individuals. We also probed the impact of PSG1 expression in a murine tumor model
      system, using subcutaneous injection of Colo-26 cells into immunocompetent BALB/c
      mice. Here, tumor growth was not affected by the expression of human PSG1. Our
      study reaffirms interest into the tumor-contextual biology of PSG proteins.

PMID- 27877218
TI  - Vitamin D3 Intake Dose and Common Cancer: A Population-Based Case Control Study
      in a Chinese Population.
AB  - Objectives: Epidemiological studies suggest that vitamin D status is associated
      inversely with risk of common cancers in western populations. This study aimed to
      investigate whether vitamin D is associated with risk of common cancers in
      Chinese population. Methods: A population-based retrospective case-control study
      was conducted analyzing data retrieved from the Catastrophic Illness Patient
      Databases (CIPD) and longitudinal health insurance database (LHID) from January
      1, 2010 to December 31, 2011and January 1, 2000 to December 31, 2011,
      respectively. Cases were identified as subjects diagnosed with site-specific
      cancers (International Classification of Diseases, Ninth Revision,) and frequency
      matched to select controls. Use of vitamin D3 was compared between two groups.
      Odds ratios (ORs) were employed to quantify the risk associated with exposure to
      vitamin D3 by logistic regression. Results: There were 1.21% (1961/161806)
      patients in cases and 0.67 % (1092/161806) patients in controls identified were
      vitamin D3 users. Overall risk of cancers associated with vitamin D3 users was
      1.67 (95% CI:1.55 -1.81). Among these, the risk of kidney cancer and bladder
      cancer associated with intakes of vitamin D3 were significant (OR 2.59; 95% CI
      1.81-3.70; OR 4.97; 95% CI 4.40-5.60) in an adjusted model. In further
      stratification analysis, we found a statistically significant risk of bladder
      cancer associated with high intake of vitamin D3. Except this, no statistically
      significant risk of other site-specific cancers associated with high intake of
      vitamin D3. Conclusion: Except bladder cancer in stratification analysis, we
      observed no statistically significant association between high intake of vitamin
      D3 and other site-specific cancers.

PMID- 27877219
TI  - An Overview of Genetic Changes and Risk of Pancreatic Ductal Adenocarcinoma.
AB  - The pancreatic carcinoma is a leading cause of death in cancer carriers
      worldwide. The early diagnostic is difficult due to late stage during diagnosis,
      lack of characteristic symptoms and also multifactor basis. In cancer development
      take part both, environmental and genetic factors, alone or in conjunction with
      each other. The nonspecific biomarkers of cancers are a reason for the search for
      more accurate factors which allow for fast and personalized diagnostics. Some of
      cancers have identified molecular (metabolic, biochemical or genetic) markers but
      in most cases the only clue is patient's interview and abnormal levels of organ
      functions markers. Possible genetic basis of cancer suggests to widen studies on
      connection between environmental factors with both, nuclear and mitochondrial,
      genes changes.

PMID- 27877220
TI  - AIB1 Genomic Amplification Predicts Poor Clinical Outcomes in Female Glioma
      Patients.
AB  - Amplified in breast cancer 1 (AIB1) gene, a coactivator for steroid receptor, is
      frequently amplified in diverse cancers and is considered as an oncogene in
      tumorigenesis. However, the prognostic significance of AIB1 amplification in
      gliomas remains totally unclear. In this study, 115 gliomas and 16 benign
      meningiomas as control subjects were enrolled, and the copy number of AIB1 was
      analyzed in these samples. In addition, we explored potential correlation of AIB1
      amplification with clinicopathological characteristics and clinical outcomes of
      glioma patients. Our data showed that glioma samples exhibited a significantly
      higher AIB1 copy number than control subjects as determined by quantitative
      polymerase chain reaction (qPCR) approach. Moreover, univariate analysis showed
      that AIB1 amplification (>=3.5 copies) was strongly correlated with cancer
      related death (P =0.03). Interestingly, our data revealed a significant
      association of AIB1 amplification with WHO grade (P =0.03), tumor recurrence (P
      =0.03) and survival status (P =0.03) in female patients but not in male patients.
      Multivariate analysis further demonstrated that AIB1 amplification was
      independent factor for cancer-related death in female patients. Importantly, AIB1
      amplification was closely relevant to worse survival in female patients (P
      =0.001), but not in male patients (P =1.00). In addition, the patients with AIB1
      amplification were resistant to radiotherapy. Altogether, our data demonstrate
      that AIB1 amplification is a common genetic event in glioma tumorigenesis, and
      suggest that AIB1 amplification is not only a prognostic factor for poor clinical
      outcomes in glioma patients, but also a predictor of radiotherapy resistance in
      gliomas.

PMID- 27877221
TI  - The Impact of Diabetes on the Risk of Prostate Cancer Development according to
      Body Mass Index: A 10-year Nationwide Cohort Study.
AB  - Purpose: We examined the association between obesity and prostate cancer both
      with and without diabetic patients included in the analysis using nationally
      representative data of the Korean population from the National Health Insurance
      System (NHIS). Materials and Methods: Of the 424,712 participants who underwent
      health examinations in 2002-2008, 139,519 men >=40 years old and without prostate
      cancer were followed from the beginning of 2002 to the end of 2012. Multivariate
      adjusted Cox regression analysis was conducted to examine the hazard ratio (HR)
      and 95% confidence interval (CI) for the association between prostate cancer and
      body mass index (BMI) both with and without diabetes. Results: The HR for
      prostate cancer according to the existence of diabetes was stratified by BMI in
      both age- and multivariable-adjusted models. In the population without diabetes,
      the HR for prostate cancer significantly increased as BMI increased beyond the
      reference range in a model adjusted for age and multiple variables; however, the
      increase in the HR was small. In the population with diabetes, the HR for
      prostate cancer significantly increased as BMI increased from < 18.5 kg/m2 to
      within the reference range (18.5 to 22.9) in the multivariable-adjusted model. In
      addition, a marked decrease in HR in the population with BMI of < 18.5 kg/m2 was
      seen compared to the reference or higher BMI population. Conclusion: This
      population-based study shows the evidence of association between obesity and
      development of prostate cancer, and the risk increases vary according to the
      change of BMI category and the existence of diabetes.

PMID- 27877223
TI  - Prognostic impact of hormone receptor- and HER2-defined subtypes in inflammatory
      breast cancer treated with high-dose chemotherapy: a retrospective study.
AB  - Purpose: Studies examining high-dose chemotherapy with autologous hematopoietic
      stem cell transplantation (HDC-AHSCT) strategies in inflammatory breast cancer
      (IBC), showed encouraging results in terms of disease-free survival (DFS), and
      overall survival (OS). The lack of data regarding HER2 status in all of these
      studies prevented any prognostic analysis involving breast cancer subtypes.
      Methods: All consecutive female patients treated for IBC with HDC and AHSCT at
      Institut Paoli-Calmettes between 2003 and 2012 were included. Since 2005,
      trastuzumab was included in initial treatment. Patient, tumor and treatment
      characteristics were collected. Patients were categorized in three subtypes based
      on hormonal receptor (HR) and HER2 status of the primary tumor: Luminal,
      (HR+/HER2-), HER2 (HER2+, any HR), and triple negative (TN) (HER2- and HR-). The
      main objective was the analysis of OS according to the IHC subtypes. Results:
      Sixty-seven patients were included. Eleven patients received trastuzumab. Median
      follow up was 80.04 months (95% CI 73.2-88.08). Five-year OS and DFS for the
      whole population patients were 74% (95% CI 61-83) and 65 % (95% CI 52-75),
      respectively. OS differed across subtypes (p=0.057) : HER2 subgroup appeared to
      have the best prognosis with a 5-year OS of 89% (95% CI 64-97) compared to 57%
      (95% CI 33-76) for the TN subgroup (HR 5.38, 95% CI 1.14-25.44; p=0.034).
      Conclusions: In IBC patients receiving HDC-AHSCT, OS favorably compares with data
      available in the literature on similar groups of patients. TN patients carried
      the least favourable OS and HER2 patients, half of them also receiving
      trastuzumab, had the best outcome. These findings provide additional information
      and options for patients with IBC and who could potentially benefit of HDC-AHSCT.

PMID- 27877222
TI  - Hedgehog Signaling Non-Canonical Activated by Pro-Inflammatory Cytokines in
      Pancreatic Ductal Adenocarcinoma.
AB  - Hedgehog(HH) pathway is found to be activated through a manner of canonical, or
      the non-canonical HH pathways. Distinct hyperplasia stroma around tumor cells is
      supposed to express pro-inflammatory cytokines abundantly, such as tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), etc. in pancreatic
      ductal adenocarcinoma (PDAC) tissues. In this study we observed the effects of
      TNF-alpha and IL-1beta on HH pathway activation in PDAC cells, and explored their
      activation manners. Our results showed that pro-inflammatory cytokines, TNF-alpha
      and IL-1beta, could up-regulate the expression of GLI1 gene, increase its nuclear
      protein expression and promote malignant cell behaviors including migration,
      invasion, epithelial-mesenchymal transition (EMT) and drug resistance as well.
      Moreover, GLI1 promoter-reporter assay in combination with blocking either NF
      kappaB or Smoothened (SMO) suggested that TNF-alpha and IL-1beta could
      transcriptionally up-regulate expression of GLI1 completely via NF-kappaB,
      whereas ablation of SMO could not completely attenuate the regulation effects of
      TNF-alpha and IL-1beta on GLI1 expression. Collectively, our results indicated
      that TNF-alpha and IL-1beta in hyperplasia stroma can promote the PDAC cell
      development by activating HH pathway, through both the canonical and non
      canonical HH activation ways.

PMID- 27877224
TI  - The role of copper transporter ATP7A in platinum-resistance of esophageal
      squamous cell cancer (ESCC).
AB  - Purpose: Platinum derivatives, such as cisplatin (DDP), carboplatin and
      oxaliplatin, are widely used components of modern cancer chemotherapy including
      esophageal squamous cell cancer (ESCC). However, their roles are limited by the
      impact of intrinsic/acquired resistance mechanisms on tumor responses. Recent
      studies have shown that the mammalian copper transporters CTR1, ATP7A and ATP7B
      are involved in cisplatin-resistance to some cancers. Methods: The cytotoxicities
      of DDP in different cell lines were determined using the MTT assay. To determine
      whether knockdown the expression of ATP7A could reverse the platinum-resistance
      of EC109/DDP cells or not, we used RNA interference system to explore the role of
      ATP7A in platinum resistance. Results: We found that DDP-resistant cell sublines
      EC109/DDP (8.490 folds) showed cross-resistance to carboplatin (5.27 folds) and
      oxaliplatin (4.12 folds). ATP7A expressions in DDP-resistant cell sublines
      (EC109/DDP) were much higher than DDP-sensitive cell lines (EC109) at both mRNA
      and protein levels. ATP7A targeted small interfering RNA duplex at 100nM final
      concentration added into DDP-resistant cancer cells (EC109/DDP) markedly
      inhibited the expression of ATP7A as determined by Western blot (83.0%) and
      partially reversed DDP-resistance (37.09%), moreover, it also increased cell
      apoptosis at different DDP concentrations. Conclusions: These findings indicate
      that ATP7A high expression plays an important role in platinum-resistance of
      ESCC. This study sheds light on platinum resistance in ESCC patients and may have
      implications for therapeutic reversal of drug resistance.

PMID- 27877225
TI  - Anti-cancer and Sensibilisation Effect of Triptolide on Human Epithelial Ovarian
      Cancer.
AB  - Introduction: Advanced ovarian cancer is the main cause of ovarian cancer deaths,
      and it is important to seek safe and effective phytochemicals to suppress cancer
      or lower the chemotherapy resistance of ovarian cancer. Methods: This study
      evaluated the effect of Triptolide (TPL) on the proliferation, cycle
      distribution, apoptosis, and ultra-structure of COC1/DDP cells in vitro, as well
      as the anti-cancer effect and sensibilisation effect of TPL in vivo. Results: The
      results indicated that TPL could significantly inhibit the growth of COC1/DDP
      cells (P<0.05), and 3 ng/ml TPL and 50 ng/ml TPL made COC1/DDP cells present
      obvious apoptosis characteristics and arrest 35% and 55% of COC/DDP cells in the
      G0/G1 phase, respectively (P<0.05). The animal experiments also indicated that
      0.1mg/kg.d TPL significantly reduced the tumour weight and the spleen cell
      transformation rate (SI), and it lowered the inflammatory factors IL-2 and TNF-a
      in rat serum (P<0.05). Moreover, the significant reduction of p-Akt and p
      GSK3beta made the TPL+DDP possess the highest apoptosis rate [(51.13+/-3.325)%]
      in COC1/DDP cells. Conclusions: TPL used in combination with DDP may produce a
      synergistic anti-cancer effect that warrants further investigation for its
      potential clinical applications in the treatment of epithelial ovarian cancer.

PMID- 27877227
TI  - Incidence and predictors of Bone Metastases (BM) and Skeletal-Related Events
      (SREs) in Small Cell Lung Cancer (SCLC): A Swiss patient cohort.
AB  - Objectives: Bone metastases (BM) and skeletal-related events (SREs) are frequent
      complications in patients with lung cancer. Whereas in non-small-cell lung cancer
      (NSCLC) incidence, prognostic impact, and risk factors are well established,
      there is only little knowledge in patients with small cell lung cancer (SCLC). We
      retrospectively evaluated the incidence of BM, SRE and their treatment in a SCLC
      patient cohort treated at our hospital. We further assessed the role of Lactate
      Dehydrogenase (LDH), a possible predictor of BM development in SCLC patients.
      Materials and Methods: We retrospectively analyzed patients with the diagnosis of
      SCLC for BM, SRE, overall treatment patterns, outcome and established prognostic
      parameters by record review. The prognostic role of LDH was tested using
      univariate longitudinal regression analysis. Results: We identified 92
      consecutive patients with SCLC diagnosed between 2000 and 2010 at our
      institution. Overall, 36.9% presented with BM at first diagnosis. Median time to
      BM from first diagnosis was 14.8 months (range) in limited disease (LD) and 0.9
      months (range) in extensive disease (ED). The overall incidence of SRE was 18.4%.
      Only 19.6% of patients with BM were initially treated with bisphosphonates.
      Conclusions: Elevated LDH, as well as age >=75 years were independent predictors
      for BM development in SCLC patients. Although SREs are relevant complications in
      SCLC, early antiresorptive treatment of BM to reduce the risk of SREs was rare.
      LDH served as a predictive factor for BM development in our SCLC cohort and
      therefore should be taken into account in future randomized controlled trials.

PMID- 27877226
TI  - Rac1 overexpression is correlated with epithelial mesenchymal transition and
      predicts poor prognosis in non-small cell lung cancer.
AB  - Objective: Ras-related C3 botulinum toxin substrate1(Rac1) and epithelial
      mesenchymal transition (EMT) are key therapeutic targets in cancer. We
      investigated the clinical significance of Rac1 and markers of EMT expression in
      non-small cell lung cancer (NSCLC), and their possible correlation with EMT
      phenotype. Methods: Immunohistochemistry was used to assess the expression of
      Rac1, Snail1, Twist1, N-cadherin (N-cad), Vimentin (Vim), and E-cadherin (E-cad)
      in 153 NSCLC paraffin-embedded specimens and 45 normal specimens adjacent to
      tumors. The correlation of Rac1 and EMT markers with clinicopathological
      characteristics and the relationship between the protein levels and progression
      free survival (PFS) and overall survival (OS) were analyzed. Results: Compared
      with non-tumor tissues, the NSCLC tissues showed marked elevation in the levels
      of Rac1, Snail1, Twist1, N-cad, and Vim levels, whereas the E-cad levels were
      significantly decreased (P < 0.05). The aberrant expression of Rac1 and EMT
      markers was significantly associated with TNM stage and metastasis (P < 0.05).
      Increased expression of Rac1 may be associated with poor OS and PFS compared with
      low expression (P<0.001 and P=0.004). Significant correlations were observed
      between the EMT markers expressed and OS or PFS(P<0.01). In addition,
      multivariate analysis indicated that the expression of Rac1, Snail1, Twist1, N
      cad, Vim, and E-cad was an independent prognostic factor in NSCLC. Interestingly,
      Rac1 expression was positively correlated with Snail1, Twist1, N-cad, and Vim
      levels (r=0.563, r=0.440, r=0.247 r=0.536, P<0.01, respectively) and negatively
      correlated with E-cad levels (r=-0.464, P<0.001) in NSCLC tissues. Rac1, Twist,
      Snail1, Vim and N-cad were highly expressed in lung cancer patients resistant to
      radiotherapy, while E-cad was poorly expressed. Conclusion: Rac1 may promote
      NSCLC progression and metastasis via EMT, which may be considered as a potential
      therapeutic target.

PMID- 27877228
TI  - Lymphangiogenesis in Classical Hodgkin Lymphoma - Preliminary Study with
      Clinicopathological Correlations.
AB  - A role for lymphangiogenesis in metastatic breast and prostate cancers has been
      suggested recently. The relevance of lymphangiogenesis in cancer as a rule, and
      more specifically in classical Hodgkin lymphoma, is poorly understood in
      comparison with that of angiogenesis. In a preliminary (pilot) study we have
      investigated the role of lymphatic vessels growth in 19 cases of classical
      Hodgkin lymphoma stained with the D2-40 (podoplanin) antibody. In each case,
      three lymphatic vessels hot spots were scrutinized twice. Of the 57 hot spots
      thus identified, we chose 15 at random for photography, microvessel counting and
      image analysis. We determined the mean perimeter, surface area, major axis length
      and complexity factor for each hot spot and correlated them with clinical and
      biological features of classical Hodgkin lymphoma. No correlations were found
      with clinical features. No associations were noted with the standard immuno
      markers of classical Hodgkin lymphoma. However, significant inverse correlations
      were shown with pRb, BAX and IkappaB-alpha expression. The mean lymphatic major
      axis length was inversely correlated with the complexity factor. Last, we carried
      out an additional clinicopathological correlation of the expression of pRb, BAX
      and IkappaB-alpha in a cohort of classical Hodgkin lymphoma patients previously
      published.

PMID- 27877229
TI  - Co-expression of Achaete-Scute Homologue-1 and Calcitonin Gene-Related Peptide
      during NNK-Induced Pulmonary Neuroendocrine Hyperplasia and Carcinogenesis in
      Hamsters.
AB  - Achaete-scute homologue-1 or ASCL1 (MASH1, hASH1) plays roles in neural
      development and pulmonary neuroendocrine (NE) differentiation, and it is
      expressed in certain lung cancers. This study was aimed to assess whether and/or
      how ASCL1 plays a role in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      induced pulmonary NE hyperplasia and carcinogenesis in hamsters. Hamsters were
      injected 3 times weekly with either NNK or solvent alone (control) for treatment
      periods of 6 and 24 weeks, both without and with 6-week recovery.
      Immunohistochemical analysis was carried out to examine the expressions of ASCL1,
      CGRP (calcitonin gene-related peptide), secretoglobin SCGB1A1 (club [Clara] cell
      specific 10 kD protein, CC10, CCSP), synaptophysin (SYP), and PCNA (proliferating
      cell nuclear antigen). The number of ASCL1-expressing NE foci per airway
      increased from 0.8 in controls to 1.6 and 2.0 during NNK exposure for 6 and 24
      weeks, respectively, and the number of cells per foci doubled after NNK exposure.
      Most ASCL1-expressing cells in NEBs (neuroepithelial bodies) were also CGRP
      immunoreactive; NNK enhanced this co-expression with CGRP, a NE marker with known
      proliferation-promoting properties. NNK also increased PCNA expression within NE
      foci. NNK-induced tumors showed no immunoreactivity for NE markers. This study
      confirms ASCL1 as an excellent marker for pulmonary NE cells and demonstrates
      CGRP co-expression in ASCL1-positive NEB cells participating in NNK-induced NE
      hyperplasia.

PMID- 27877230
TI  - Transcriptional cofactor Mask2 is required for YAP-induced cell growth and
      migration in bladder cancer cell.
AB  - The highly conserved Hippo signaling pathway is an important pathway involved in
      tumorigenesis and development. In previous studies, YAP, the transcription
      coactivator of Hippo pathway, is found to be highly expressed in many clinical
      bladder cancer samples. To investigate the function of YAP and its cofactor Mask2
      in bladder cancer, we overexpress YAP in bladder cancer cells and discover that
      YAP is able to promote bladder cancer cell growth and migration. In addition, we
      provide evidence that knockdown of Mask2 is able to repress bladder cancer cell
      growth and migration. Furthermore, we demonstrate knockdown of Mask2 is able to
      inhibit bladder cancer cell growth and migration induced by the excessive YAP. To
      explain the function of YAP/Mask2 complex in bladder cancer, we check the target
      genes' expression of Hippo signaling pathway involved in cell growth and
      migration and find overexpressed YAP is able to upregulate the target genes'
      expression while depletion of Mask2 downregulates them. Taken together, we
      demonstrate that Mask2 is required for the function of bladder cancer cell growth
      and migration induced by YAP via the target genes of Hippo pathway.

PMID- 27877231
TI  - Chemomodulatory Potential of Bartogenic Acid Against DMBA/Croton Oil Induced Two
      Step Skin Carcinogenesis in Mice.
AB  - Barringtonia racemosa fruits are believed to be useful in cancer treatment in
      Ayurveda, the Indian system of medicine. In present study, bartogenic acid (BA),
      a triterpenoid constituent of Barringtonia fruits was evaluated for its
      cytotoxicity property using the human skin carcinoma cell line (SCC-13) and human
      peripheral blood mononuclear cells (PBMC). The chemopreventive efficacy of BA was
      evaluated against the DMBA/Croton oil-induced skin carcinogenesis in mice.BA was
      orally administered at the doses of 1, 2 or 4 mg/kg/day or applied topically
      every day for 12 weeks following DMBA application. The in vitro data from cell
      lines revealed that BA induces cytotoxicity against the SCC-13 cells (IC50=7.5
      uM). It was found 4.05 times more selective to exert cytotoxicity against SCC-13
      as compared to the PBMC (IC50=30.4 uM). The in vivo datacollected from mice model
      of DMBA/Croton oil-induced skin carcinogenesis revealed that BA administered
      orally or applied topically, both reduced the precancerous skin lesions andthe
      incidence of tumor bearing. The oral doses of BA (2 and 4 mg/kg) and topical
      treatment significantly reduced the incidence and number of skin papillomas. At
      these doses, BA also increased the activities of catalase and superoxide
      dismutase and induced an increase in glutathionecontent and inhibited lipid
      peroxidation in the skin. These findings reveal the chemopreventive efficacy of
      BA and also demonstrate that it contributes to the cytotoxic and antioxidative
      effects of Barringtonia racemosa fruits. The study also validates the traditional
      claims of Barringtonia fruits and provides a scientific basis of its
      chemopreventive property.

PMID- 27877232
TI  - A Novel Prognostic Score, Based on Preoperative Nutritional Status, Predicts
      Outcomes of Patients after Curative Resection for Gastric Cancer.
AB  - PURPOSE: We aimed to determine whether preoperative nutritional status (PNS) was
      a valuable predictor of outcome in patients with gastric cancer (GC). METHODS: We
      retrospectively evaluated 1320 patients with GC undergoing curative resection.
      The PNS score was constructed based on four objective and easily measurable
      criteria: prognostic nutritional index (PNI) score 1, serum albumin <35 g/L, body
      mass index (BMI) <18.5 kg/m2, or preoperative weight loss >=5% of body weight.
      The PNS score was 2 for patients who met three or four criteria, 1 for those who
      met one or two criteria, and 0 for those who didn't meet all of these criteria.
      RESULTS: The overall survival (OS) rates in patients with PNS scores 0, 1, and 2
      were 59.1%, 42.4%, and 23.4%, respectively (P < 0.001). Multivariate analyses
      revealed the PNS was an independent predictor for OS (HR for PNS 1 and PNS 2:
      1.497, 95 % CI: 1.230-1.820 and 2.434, 95 % CI: 1.773-3.340, respectively; p <
      0.001). Furthermore, 5-year OS ranged from 92% (stage I) to 37% (stage III),
      while the combination of TNM and PNS stratified 5-year OS from 95% (TNM I, PNS 0)
      to 19% (TNM III, PNS 3). Of note, the prognostic significance of PNS was still
      maintained when stratified by TNM stage, age, sex, tumor size, anemia and
      adjuvant chemotherapy (All P < 0.05). CONCLUSIONS: The PNS, a novel nutritional
      based prognostic score, is independently associated with OS in GC. Prospective
      studies are needed to validate its clinical utility.

PMID- 27877233
TI  - The Impact of Clinical Stage on Radiation Doses to Organs at Risk Following
      Intensity-modulated Radiotherapy in Nasopharyngeal Carcinoma: A Prospective
      Analysis.
AB  - Background: The development of intensity-modulated radiotherapy (IMRT) has
      revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of
      this study was to investigate the impact of clinical stage on radiation doses to
      organs at risk (OARs) in NPC. Material and Methods: One hundred and forty-eight
      patients with newly diagnosed and untreated NPC were prospectively enrolled.
      Based on the anatomic definition and pathogenesis of radiation induced injury, a
      total of 28 OARs surrounding the nasopharynx were contoured on axial computed
      tomography (CT) planning images in each patient. Dose-volume histograms, as well
      as the mean and maximal doses for each structure, were calculated. Results:
      Radiation doses to 15 OARs (including the brain stem, temporal lobe and eye) were
      positively correlated with T stage, the radiation doses to 13 OARs (including the
      brachial plexus, parotid and thyroid) increased significantly with N stage, and
      the radiation doses to the spinal cord and mandible had no association with T or
      N stage. Based on the characteristic of excess rates, 9 OARs (e.g. spinal cord,
      eye, trachea, and et al.) met tolerance doses easily in all stages, 9 OARs (e.g.
      brain stem, temporal lobe, brachial plexus, and et al.) easily in early stages
      but with difficulty in advanced stages, and 10 OARs (e.g. cochlea, parotid,
      thyroid, and et al.) with difficulty in all stages. Conclusions: The radiation
      doses to most of OARs are associated with T or N stage, and there are three kinds
      of patterns for them: 1) meet tolerance doses easily in all stages; 2) meet
      tolerance doses easily in early stages but with difficulty in advanced stages;
      and 3) meet tolerance doses with difficulty in all stages.

PMID- 27877234
TI  - Light-Mediated Deep-Tissue Theranostics.
AB  - This theme issue provides an overview on recent developments of light-mediated
      imaging and therapy approaches, with an emphasis on those that transcend the
      shallow tissue penetration dogma.

PMID- 27877235
TI  - X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and
      Photodynamic Therapy.
AB  - Conventional photodynamic therapy (PDT)'s clinical application is limited by
      depth of penetration by light. To address the issue, we have recently developed X
      ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source
      to activate a PDT process. In addition to breaking the shallow tissue penetration
      dogma, our studies found more efficient tumor cell killing with X-PDT than with
      radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have
      not been elucidated. In the present study, we investigate the mechanisms of
      action of X-PDT on cancer cells. Our results demonstrate that X-PDT is more than
      just a PDT derivative but is essentially a PDT and RT combination. The two
      modalities target different cellular components (cell membrane and DNA,
      respectively), leading to enhanced therapy effects. As a result, X-PDT not only
      reduces short-term viability of cancer cells but also their clonogenecity in the
      long-run. From this perspective, X-PDT can also be viewed as a unique
      radiosensitizing method, and as such it affords clear advantages over RT in tumor
      therapy, especially for radioresistant cells. This is demonstrated not only in
      vitro but also in vivo with H1299 tumors that were either subcutaneously
      inoculated or implanted into the lung of mice. These findings and advances are of
      great importance to the developments of X-PDT as a novel treatment modality
      against cancer.

PMID- 27877236
TI  - Core-Shell Nanostars for Multimodal Therapy and Imaging.
AB  - The coupling of diagnostic capability and effective therapy in a single
      multifunctional nanomedicine is desirable but remains challenging. Here, we
      developed multifunctional nanoparticles consisting of a gold nanostar (AuNS) core
      with a shell of metal-drug coordination polymer (CP). The AuNS core enabled
      plasmonic photothermal effect and two-photon photoluminescence (TPL), while the
      CP shell of gadolinium and gemcitabine monophosphate allowed chemotherapy and MRI
      imaging. The AuNS@CP nanoparticles exhibited a strong T1 contrast signal and
      could monitor the localization of nanoparticles in vivo through noninvasive MR
      imaging, while intravital TPL imaging could be used to study nanoparticle
      behavior in tumors at the microscopic level. The combination of photothermal
      therapy and chemotherapy inhibited tumor growth in vivo.

PMID- 27877237
TI  - Near Infrared Fluorescent Nanoparticles Derived from Hyaluronic Acid Improve
      Tumor Contrast for Image-Guided Surgery.
AB  - Tumor tissue that remains undetected at the primary surgical site can cause tumor
      recurrence, repeat surgery, and treatment strategy alterations that impose a
      significant patient and healthcare burden. Intraoperative near infrared
      fluorescence (NIRF) imaging is one potential method to identify remaining tumor
      by visualization of NIR fluorophores that are preferentially localized to the
      tumor. This requires development of fluorophores that consistently identify tumor
      tissue in different patients and tumor types. In this study we examined a panel
      of NIRF contrast agents consisting of polymeric nanoparticle (NP) formulations
      derived from hyaluronic acid (HA), with either physically entrapped indocyanine
      green (ICG) or covalently conjugated Cy7.5. Using orthotopic human breast cancer
      MDA-MB-231 xenografts in nude mice we identified two lead formulations. One,
      NanoICGPBA, with physicochemically entrapped ICG, showed 2.3-fold greater tumor
      contrast than ICG alone at 24 h (p < 0.01), and another, NanoCy7.5100-H, with
      covalently conjugated Cy7.5, showed 74-fold greater tumor contrast than Cy7.5
      alone at 24 h (p < 0.0001). These two lead formulations were then tested in
      immune competent BALB/c mice bearing orthotopic 4T1 breast cancer tumors.
      NanoICGPBA showed 2.2-fold greater contrast than ICG alone (p < 0.0001), and
      NanoCy7.5100-H showed 14.8-fold greater contrast than Cy7.5 alone (p < 0.0001).
      Furthermore, both NanoICGPBA and NanoCy7.5100-H provided strong tumor enhancement
      using image-guided surgery in mice bearing 4T1 tumors. These studies demonstrate
      the efficacy of a panel of HA-derived NPs in delineating tumors in vivo, and
      identifies promising formulations that can be used for future in vivo tumor
      removal efficacy studies.

PMID- 27877238
TI  - Sphingomyelin Liposomes Containing Porphyrin-phospholipid for Irinotecan
      Chemophototherapy.
AB  - Porphyrin-phospholipid (PoP) liposomes can entrap anti-cancer agents and release
      them in response to near infrared (NIR) light. Doxorubicin, when remotely loaded
      via an ammonium sulfate gradient at a high drug-to-lipid ratio, formed elongated
      crystals that altered liposome morphology and could not be loaded into liposomes
      with higher PoP content. On the other hand, irinotecan could also be remotely
      loaded but did not form large crystals and did not induce liposome elongation.
      The loading, stability, and NIR light-triggered release of irinotecan in PoP
      liposomes was altered by the types of lipids used and the presence of PEGylation.
      Sphingomyelin, which has been explored previously for liposomal irinotecan, was
      found to produce liposomes with relatively improved serum stability and rapid NIR
      light-triggered drug release. PoP liposomes composed from sphingomyelin,
      cholesterol and 2 molar percent PoP rapidly released irinotecan in vivo in
      response to NIR irradiation as monitored by intravital microscopy and also
      induced effective tumor eradication in mice bearing MIA Paca-2 subcutaneous tumor
      xenografts.

PMID- 27877240
TI  - ROS-Responsive Mitochondria-Targeting Blended Nanoparticles: Chemo- and
      Photodynamic Synergistic Therapy for Lung Cancer with On-Demand Drug Release upon
      Irradiation with a Single Light Source.
AB  - Mitochondria in cancer cells maintain a more negative membrane potential than
      normal cells. Mitochondria are the primary source of cellular reactive oxygen
      species (ROS), which are necessary for photodynamic therapy. Thus, the strategy
      of targeting mitochondria can maximize the photodynamic therapeutic efficiency
      for cancer. Here we report, for the first time, synthesis of a new mitochondria
      targeting drug delivery system, ZnPc/CPT-TPPNPs. To synthesize this novel
      compound, polyethylene glycol was functionalized with thioketal linker-modified
      camptothecin (TL-CPT) and triphenylphosphonium to form the block copolymer, TL
      CPT-PEG1K-TPP. The ZnPc/CPT-TPPNPs was constructed for delivery of the
      photosensitizer Zinc phthalocyanine (ZnPc) by blending the block copolymer TL-CPT
      PEG1K-TPP with 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy
      (polyethylene glycol)] (DSPE-PEG).Triphenylphosphine can accumulate selectively
      several hundred-fold within mitochondria. The thioketal linker is ROS-responsive
      and CPT can be released upon ROS cleavage. We also show that the ZnPc loaded in
      ZnPc/CPT-TPPNPs absorbed the 633 nm laser to produce ROS, which could be utilized
      both in photodynamic therapy and to cleave the thioketal linker thereby releasing
      camptothecin for chemotherapy. Thus, the mitochondria-targeting nanoparticles
      could elevate photodynamic therapeutic efficacy. Our results showed that surface
      modification of the nanoparticles with triphenylphosphine cations facilitated
      efficient subcellular delivery of the photosensitizer to mitochondria. The
      nanoparticles had a good ROS-responsive effect to release CPT, which could
      transfer to the nucleus and interfere with DNA replication as a
      topoisomeraseIinhibitor. Thus, the blended nanoparticles provide a new promising
      approach as a mitochondria-targeting ROS-activated chemo- and photodynamic
      therapy with a single light source for lung cancer.

PMID- 27877239
TI  - NIR-Laser-Controlled Drug Release from DOX/IR-780-Loaded Temperature-Sensitive
      Liposomes for Chemo-Photothermal Synergistic Tumor Therapy.
AB  - NIR laser-induced photothermal therapy (PTT) through near-infrared agents has
      demonstrated the great potential in solid tumor ablation. However, the nonuniform
      heat distribution over tumors from PTT makes it insufficient to kill all tumor
      cells, resulting in tumor recurrence and inferior outcomes. To improve the tumor
      treatment efficacy, it is highly desirable to develop the combinational treatment
      of PTT with other modalities, especially with chemotherapeutic agents. Here we
      report a smart DOX/IR-780-loaded temperature-sensitive-liposome (DITSL) which can
      achieve NIR-laser-controlled drug release for chemo-photothermal synergistic
      tumor therapy. In this system, the liposoluble IR-780 was incorporated into the
      temperature-sensitive lipid bilayer and the soluble chemotherapeutic doxorubicin
      (DOX) was encapsulated in the hydrophilic core. The resulting DITSL is proved to
      be physiologically stable and can provide a fast and laser irradiation
      controllable DOX release in the PBS and cellular conditions. We further employed
      this nanoparticle for tumor treatment, demonstrating significantly higher tumor
      inhibition efficacy than that of DOX-loaded temperature-sensitive-liposome (DTSL)
      or IR780-loaded temperature-sensitive-liposome (ITSL) in the in vitro cells and
      in vivo animals. Histological analysis further revealed much more apoptotic
      cells, confirming the advantageous anti-tumor effect of DITSL over DTSL or ITSL.
      Our study provides a promising strategy to realize chemo-photothermal synergistic
      combination therapy for breast tumors.

PMID- 27877241
TI  - Photo-decomposable Organic Nanoparticles for Combined Tumor Optical Imaging and
      Multiple Phototherapies.
AB  - Combination of photodynamic therapy (PDT) with photothermal therapy (PTT) has
      achieved significantly improved therapeutic efficacy compared to a single
      phototherapy modality. However, most nanomaterials used for combined PDT/PTT are
      made of non-biodegradable materials (e.g., gold nanorods, carbon nanotubes, and
      graphenes) and may remain intact in the body for long time, raising concerns over
      their potential long-term toxicity. Here we report a new combined PDT/PTT
      nanomedicine, designated SP3NPs, that exhibit photo-decomposable, photodynamic
      and photothermal properties. SP3NPs were prepared by self-assembly of PEGylated
      cypate, comprising FDA-approved PEG and an ICG derivative. We confirmed the
      ability of SP3NPs to generate both singlet oxygen for a photodynamic effect and
      heat for photothermal therapy in response to NIR laser irradiation in vitro.
      Also, the unique ability of SP3NPs to undergo irreversible decomposition upon NIR
      laser irradiation was demonstrated. Further our experimental results demonstrated
      that SP3NPs strongly accumulated in tumor tissue owing to their highly PEGylated
      surface and relatively small size (~60 nm), offering subsequent imaging-guided
      combined PDT/PTT treatment that resulted in tumor eradication and prolonged
      survival of mice. Taken together, our SP3NPs described here may represent a novel
      and facile approach for next-generation theranostics with great promise for
      translation into clinical practice in the future.

PMID- 27877242
TI  - Nanoscale "fluorescent stone": Luminescent Calcium Fluoride Nanoparticles as
      Theranostic Platforms.
AB  - Calcium Fluoride (CaF2) based luminescent nanoparticles exhibit unique,
      outstanding luminescent properties, and represent promising candidates as
      nanoplatforms for theranostic applications. There is an urgent need to facilitate
      their further development and applications in diagnostics and therapeutics as a
      novel class of nanotools. Here, in this critical review, we outlined the recent
      significant progresses made in CaF2-related nanoparticles: Firstly, their
      physical chemical properties, synthesis chemistry, and nanostructure fabrication
      are summarized. Secondly, their applications in deep tissue bio-detection, drug
      delivery, imaging, cell labeling, and therapy are reviewed. The exploration of
      CaF2-based luminescent nanoparticles as multifunctional nanoscale carriers for
      imaging-guided therapy is also presented. Finally, we discuss the challenges and
      opportunities in the development of such CaF2-based platform for future
      development in regard to its theranostic applications.

PMID- 27877243
TI  - Recent Advances in Photoacoustic Imaging for Deep-Tissue Biomedical Applications.
AB  - Photoacoustic imaging (PAI), a novel imaging modality based on photoacoustic
      effect, shows great promise in biomedical applications. By converting pulsed
      laser excitation into ultrasonic emission, PAI combines the advantages of optical
      imaging and ultrasound imaging, which benefits rich contrast, high resolution and
      deep tissue penetration. In this paper, we introduced recent advances of contrast
      agents, applications, and signal enhancement strategies for PAI. The PA contrast
      agents were categorized by their components, mainly including inorganic and
      organic PA contrast agents. The applications of PAI were summarized as follows:
      deep tumor imaging, therapeutic responses monitoring, metabolic imaging, pH
      detection, enzyme detection, reactive oxygen species (ROS) detection, metal ions
      detection, and so on. The enhancement strategies of PA signals were highlighted.
      In the end, we elaborated on the challenges and provided perspectives of PAI for
      deep-tissue biomedical applications.

PMID- 27877244
TI  - Advances in Imaging Techniques and Genetically Encoded Probes for Photoacoustic
      Imaging.
AB  - Photoacoustic (PA) imaging is a rapidly emerging biomedical imaging modality that
      is capable of visualizing cellular and molecular functions with high detection
      sensitivity and spatial resolution in deep tissue. Great efforts and progress
      have been made on the development of various PA imaging technologies with
      improved resolution and sensitivity over the past two decades. Various PA probes
      with high contrast have also been extensively developed, with many important
      biomedical applications. In comparison with chemical dyes and nanoparticles,
      genetically encoded probes offer easier labeling of defined cells within tissues
      or proteins of interest within a cell, have higher stability in vivo, and
      eliminate the need for delivery of exogenous substances. Genetically encoded
      probes have thus attracted increasing attention from researchers in engineering
      and biomedicine. In this review, we aim to provide an overview of the existing PA
      imaging technologies and genetically encoded PA probes, and describe further
      improvements in PA imaging techniques and the near-infrared photochromic protein
      BphP1, the most sensitive genetically encoded probe thus far, as well as the
      potential biomedical applications of BphP1-based PA imaging in vivo.

PMID- 27877245
TI  - Imaging Nanotherapeutics in Inflamed Vasculature by Intravital Microscopy.
AB  - Intravital microscopy (IVM) is the application of light microscopy to real time
      study biology of live animal tissues in intact and physiological conditions with
      the high spatial and temporal resolution. Advances in imaging systems, genetic
      animal models and imaging probes, IVM has offered quantitative and dynamic
      insight into cell biology, immunology, neurobiology and cancer. In this review,
      we will focus on the targeting of nanotherapeutics to inflamed vasculature. We
      will introduce the basic concept and principle of IVM and demonstrate that IVM is
      a powerful tool used to quantitatively determine the molecular mechanisms of
      interactions between nanotherapeutics and neutrophils or endothelium in living
      mice. In the future, it is needed to develop new imaging systems and novel
      imaging contrast agents to better understand molecular mechanisms of tissue
      processing of nanotherapeutics in vivo.

PMID- 27877249
TI  - Focus on materials analysis and processing in magnetic fields.

PMID- 27877250
TI  - Hydrothermal growth of ZnO nanostructures.
AB  - One-dimensional nanostructures exhibit interesting electronic and optical
      properties due to their low dimensionality leading to quantum confinement
      effects. ZnO has received lot of attention as a nanostructured material because
      of unique properties rendering it suitable for various applications. Amongst the
      different methods of synthesis of ZnO nanostructures, the hydrothermal method is
      attractive for its simplicity and environment friendly conditions. This review
      summarizes the conditions leading to the growth of different ZnO nanostructures
      using hydrothermal technique. Doping of ZnO nanostructures through hydrothermal
      method are also highlighted.

PMID- 27877251
TI  - Texturing by cooling a metallic melt in a magnetic field.
AB  - Processing in a magnetic field leads to the texturing of materials along an easy
      magnetization axis when a minimum anisotropy energy exists at the processing
      temperature; the magnetic field can be applied to a particle assembly embedded
      into a liquid, or to a solid at a high diffusion temperature close to the melting
      temperature or between the liquidus and the solidus temperatures in a region of
      partial melting. It has been shown in many experiments that texturing is easy to
      achieve in congruent and noncongruent compounds by applying the field above the
      melting temperature Tm or above the liquidus temperature of alloys. Texturing
      from a melt is successful when the overheating temperature is just a few degrees
      above Tm and fails when the processing time above Tm is too long or when the
      overheating temperature is too high; these observations indicate the presence of
      unmelted crystals above Tm with a size depending on these two variables that act
      as growth nuclei. A recent model that predicts the existence of unmelted crystals
      above the melting temperature is used to calculate their radius in a bismuth
      melt.

PMID- 27877248
TI  - Chemically engineered persistent luminescence nanoprobes for bioimaging.
AB  - Imaging nanoprobes are a group of nanosized agents developed for providing
      improved contrast for bioimaging. Among various imaging probes, optical sensors
      capable of following biological events or progresses at the cellular and
      molecular levels are actually actively developed for early detection, accurate
      diagnosis, and monitoring of the treatment of diseases. The optical activities of
      nanoprobes can be tuned on demand by chemists by engineering their composition,
      size and surface nature. This review will focus on researches devoted to the
      conception of nanoprobes with particular optical properties, called persistent
      luminescence, and their use as new powerful bioimaging agents in preclinical
      assays.

PMID- 27877247
TI  - Beyond the Barriers of Light Penetration: Strategies, Perspectives and
      Possibilities for Photodynamic Therapy.
AB  - Photodynamic therapy (PDT) is a photochemistry based treatment modality that
      involves the generation of cytotoxic species through the interactions of a
      photosensitizer molecule with light irradiation of an appropriate wavelength. PDT
      is an approved therapeutic modality for several cancers globally and in several
      cases has proved to be effective where traditional treatments have failed. The
      key parameters that determine PDT efficacy are 1. the photosensitizer (nature of
      the molecules, selectivity, and macroscopic and microscopic localization etc.),
      2. light application (wavelength, fluence, fluence rate, irradiation regimes
      etc.) and 3. the microenvironment (vascularity, hypoxic regions, stromal tissue
      density, molecular heterogeneity etc.). Over the years, several groups aimed to
      monitor and manipulate the components of these critical parameters to improve the
      effectiveness of PDT treatments. However, PDT is still misconstrued to be a
      surface treatment primarily due to the limited depths of light penetration. In
      this review, we present the recent advances, strategies and perspectives in PDT
      approaches, particularly in cancer treatment, that focus on increasing the
      'damage zone' beyond the reach of light in the body. This is enabled by a
      spectrum of approaches that range from innovative photosensitizer excitation
      strategies, increased specificity of phototoxicity, and biomodulatory approaches
      that amplify the biotherapeutic effects induced by photodynamic action. Along
      with the increasing depth of understanding of the underlying physical, chemical
      and physiological mechanisms, it is anticipated that with the convergence of
      these strategies, the clinical utility of PDT will be expanded to a powerful
      modality in the armamentarium for the management of cancer.

PMID- 27877253
TI  - Fabrication of crystal-oriented barium-bismuth titanate ceramics in high magnetic
      field and subsequent reaction sintering.
AB  - High magnetic field was applied to fabricate novel lead-free piezoelectric
      ceramics with a textured structure. A compact of crystallographically oriented
      grains was prepared by dry forming in a high magnetic field from a mixed slurry
      of bismuth titanate and barium titanate powders. Bismuth titanate particles with
      a size of about 1 MU m were used as the host material. In the forming process,
      the slurry was poured into a mold and set in a magnetic field of 10 T until
      completely dried. Bismuth titanate particles were highly oriented in the slurry
      under the magnetic field. The dried powder compact consisted of highly oriented
      bismuth titanate particles and randomly oriented barium titanate particles.
      Barium bismuth titanate ceramics with a- and b-axis orientations were
      successfully produced from the dried compact by sintering at temperatures above
      1100  degrees  C.

PMID- 27877246
TI  - Recent Advances of Light-Mediated Theranostics.
AB  - Currently, precision theranostics have been extensively demanded for the
      effective treatment of various human diseases. Currently, efficient therapy at
      the targeted disease areas still remains challenging since most available drug
      molecules lack of selectivity to the pathological sites. Among different
      approaches, light-mediated therapeutic strategy has recently emerged as a
      promising and powerful tool to precisely control the activation of therapeutic
      reagents and imaging probes in vitro and in vivo, mostly attributed to its unique
      properties including minimally invasive capability and highly spatiotemporal
      resolution. Although it has achieved initial success, the conventional strategies
      for light-mediated theranostics are mostly based on the light with short
      wavelength (e.g., UV or visible light), which may usually suffer from several
      undesired drawbacks, such as limited tissue penetration depth, unavoidable light
      absorption/scattering and potential phototoxicity to healthy tissues, etc.
      Therefore, a near-infrared (NIR) light-mediated approach on the basis of long
      wavelength light (700-1000 nm) irradiation, which displays deep-tissue
      penetration, minimized photo-damage and low autofluoresence in living systems,
      has been proposed as an inspiring alternative for precisely phototherapeutic
      applications in the last decades. Despite numerous NIR light-responsive molecules
      have been currently proposed for clinical applications, several inherent
      drawbacks, such as troublesome synthetic procedures, low water solubility and
      limited accumulation abilities in targeted areas, heavily restrict their
      applications in deep-tissue therapeutic and imaging studies. Thanks to the
      amazing properties of several nanomaterials with large extinction coefficient in
      the NIR region, the construction of NIR light responsive nanoplatforms with
      multifunctions have become promising approaches for deep-seated diseases
      diagnosis and therapy. In this review, we summarized various light-triggered
      theranostic strategies and introduced their great advances in biomedical
      applications in recent years. Moreover, some other promising light-assisted
      techniques, such as photoacoustic and Cerenkov radiation, were also systemically
      discussed. Finally, the potential challenges and future perspectives for light
      mediated deep-tissue diagnosis and therapeutics were proposed.

PMID- 27877252
TI  - Using magnetic birefringence to determine the molecular arrangement of
      supramolecular nanostructures.
AB  - Supramolecular aggregates can be aligned in solution using a magnetic field.
      Because of the optical anisotropy of the molecular building blocks, the alignment
      results in an anisotropic refractive index of the solution parallel and
      perpendicular to the magnetic field. We present a model for calculating the
      magnetic birefringence, using solely the magnetic susceptibilities and optical
      polarizabilities of the molecules, for any molecular arrangement. We demonstrate
      that magnetic birefringence is a very sensitive tool for determining the
      molecular organization within supramolecular aggregates.

PMID- 27877254
TI  - Simultaneous alignment and micropatterning of carbon nanotubes using modulated
      magnetic field.
AB  - We report simultaneous alignment and micropatterning of carbon nanotubes (CNTs)
      using a high magnetic field. It is important to prepare well-dispersed CNTs for
      alignment and patterning because CNT aggregation obstructs alignment. In magnetic
      field, highly anisotropic CNTs rotate in the direction stabilized in energy.
      Owing to their diamagnetic nature, CNTs suspended in a liquid medium are trapped
      in a weak magnetic field generated by a field modulator; meanwhile, they align to
      the applied strong magnetic field. The alignment has been achieved not only in
      polymers but also in ceramic and silicone composites.

PMID- 27877255
TI  - Magnetic orientation and magnetic anisotropy in paramagnetic layered oxides
      containing rare-earth ions.
AB  - The magnetic anisotropies and easy axes of magnetization at room temperature were
      determined, and the effects of rare-earth (RE) ions were clarified for RE-based
      cuprates, RE-doped bismuth-based cuprates and RE-doped Bi-based cobaltite
      regarding the grain orientation by magnetic field. The easy axis, determined from
      the powder orientation in a static field of 10 T, depended qualitatively on the
      type of RE ion for all three systems. On the other hand, the magnetization
      measurement of the c-axis oriented powders, aligned in static or rotating fields,
      revealed that the type of RE ion strongly affected not only the directions of the
      easy axis but also the absolute value of magnetic anisotropy, and an appropriate
      choice of RE ion is required to minimize the magnetic field used for grain
      orientation. We also studied the possibility of triaxial grain orientation in
      high-critical-temperature superconductors by a modulated oval magnetic field. In
      particular, triaxial orientation was attempted in a high-oxygen-pressure phase of
      orthorhombic RE-based cuprates Y2Ba4Cu7O y . Although the experiment was
      performed in epoxy resin, which is not practical, in-plane alignment within 3
      degrees  was achieved.

PMID- 27877256
TI  - On the influence of magnetic field processing on the texture, phase assemblage
      and properties of low aspect ratio Bi2Sr2CaCu2O x /AgMg wire.
AB  - Bi2Sr2CaCu2O x /AgMg conductors are potentially important for many applications
      up to 20 K, including magnets for cryogen-free magnetic resonance imaging and
      high field nuclear magnetic resonance research. One promising approach to
      increased critical current density is partial-melt processing in the presence of
      a magnetic field which has been shown to enhance c-axis texturing of wide, thin
      tape conductors. Here, we report on low aspect ratio rectangular conductors
      processed in an 8 T magnetic field. The magnetic field is applied during
      different stages of the heat treatment process. The conductors are electrically
      characterized using four-point critical current measurements as a function of
      magnetic field and magnetic field orientation relative to the conductor. The
      superconductive transition and magnetization hysteresis are measured using a
      SQUID magnetometer. The microstructures are characterized using scanning electron
      microscopy and energy dispersive spectroscopy and analyzed using digital image
      processing. It is found that the presence of a magnetic field during split melt
      processing enhances the electrical transport and magnetic behavior, but that the
      anisotropy is not consistently affected. The magnetic field also affects
      development of interfilamentary Bi2212 bridges, and that this depends on the
      initial shape of the Bi2212 filament. At least two behaviors are identified; one
      impacts the oxide phase assemblage and the other impacts textured growth.

PMID- 27877257
TI  - Effects of high magnetic fields on solidified structures of Mn-90.4 wt% Sb
      hypoeutectic alloy.
AB  - Mn-90.4 wt% Sb alloy specimens were solidified under both uniform magnetic field
      and magnetic field gradient conditions. The solidification behavior was examined
      to elucidate the effects of high magnetic fields on the solidified structure
      evolution of this hypoeutectic alloy. The macrostructures on the longitudinal
      section of the alloys were investigated by optical microscopy and x-ray
      diffraction (XRD). The volume fraction of primary MnSb phases and the interrod
      spacing of the eutectic were measured by metallographic analysis. It was found
      that the segregation of the primary MnSb particles at the certain regions of the
      specimens occurred under the influence of high magnetic field gradients. The MnSb
      phases obtained under magnetic fields were oriented with their (h0 l) planes
      along the direction of the magnetic field. Both the volume fraction of primary
      MnSb phases and the interrod spacing of the eutectic were decreased upon the
      application of the high magnetic fields.

PMID- 27877258
TI  - Crystal growth nucleation and Fermi energy equalization of intrinsic spherical
      nuclei in glass-forming melts.
AB  - The energy saving resulting from the equalization of Fermi energies of a crystal
      and its melt is added to the Gibbs free-energy change DeltaG2ls associated with a
      crystal formation in glass-forming melts. This negative contribution being a
      fraction epsilon ls(T) of the fusion heat is created by the electrostatic
      potential energy -U0 resulting from the electron transfer from the crystal to the
      melt and is maximum at the melting temperature Tm in agreement with a
      thermodynamics constraint. The homogeneous nucleation critical temperature T2,
      the nucleation critical barrier DeltaG2ls*/kBT and the critical radius R*2ls are
      determined as functions of epsilonls(T). In bulk metallic glass forming melts,
      epsilonls(T) and T2 only depend on the free-volume disappearance temperature T0l,
      and epsilonls(Tm) is larger than 1 (T0l>Tm/3); in conventional undercooled melts
      epsilonls(Tm) is smaller than 1 (T0l>Tm/3). Unmelted intrinsic crystals act as
      growth nuclei reducing DeltaG2ls*/kBT and the nucleation time. The temperature
      time transformation diagrams of Mg65Y10Cu25, Zr41.2Ti13.8Cu12.5Ni10Be22.5,
      Pd43Cu27 Ni10P20, Fe83B17 and Ni melts are predicted using classic nucleation
      models including time lags in transient nucleation, by varying the intrinsic
      nucleus contribution to the reduction of DeltaG2ls*/kBT. The energy-saving
      coefficient epsilon nm(T) of an unmelted crystal of radius Rnm is reduced when
      Rnm ?R*2ls; epsilonnm is quantified and corresponds to the first energy level of
      one s-electron moving in vacuum in the same spherical attractive potential -U0
      despite the fact that the charge screening is built by many-body effects.

PMID- 27877259
TI  - Control of lattice spacing in a triangular lattice of feeble magnetic particles
      formed by induced magnetic dipole interactions.
AB  - We studied methods of controlling the spacing between particles in the triangular
      lattice formed by feeble magnetic particles through induced magnetic dipole
      interaction. Formation of a triangular lattice is described by the balance
      between the magnetic force and the interaction of induced magnetic dipoles. The
      intensity of the magnetic force is proportional to the volume of particles V and
      the difference in the magnetic susceptibilities between the particles and the
      surrounding medium Deltachi. On the other hand, the intensity of the induced
      magnetic dipole interaction depends on the square of V and Deltachi. Therefore,
      altering the magnetic susceptibility difference by changing the susceptibility of
      the surrounding medium, volume of the particles, and intensity and spatial
      distribution of the applied magnetic field effectively controls the distance
      between the particles. In this study, these three methods were evaluated through
      experiment and molecular dynamics simulations. The distance between the
      particles, i.e. the lattice constant of the triangular lattice, was varied from
      1.7 to 4.0 in units of the particle diameter. Formation of self-organized
      triangular lattice through the induced magnetic dipole interaction is based on
      magnetism, a physical property that all materials have. Therefore, this
      phenomenon is applicable to any materials of any size. Consequently, structure
      formation through induced magnetic dipole interaction is a potential way of
      fabricating materials with ordered structures.

PMID- 27877260
TI  - Numerical simulation of chainlike cluster movement of feeble magnetic particles
      by induced magnetic dipole moment under high magnetic fields.
AB  - In this paper, the motion of a chainlike cluster of feeble magnetic particles
      induced by high magnetic field is discussed on the basis of the results of
      numerical simulations. The simulations were performed on glass particles with a
      diameter of 0.8 mm; and the viscosity, applied magnetic field and magnetic
      properties of the surrounding medium were changed. In addition to the magnetic
      field and the difference in magnetic susceptibility between the particles and the
      surrounding medium, the obtained results indicate that the viscosity is an
      essential factor for the formation of the chainlike alignment of feeble magnetic
      particles. We also carried out simulations using glass particles with a smaller
      diameter of 0.1 mm. Chainlike clusters were produced similar to those of
      ferromagnetic particles formed in a ferromagnetic fluid.

PMID- 27877261
TI  - Study of flow fractionation characteristics of magnetic chromatography utilizing
      high-temperature superconducting bulk magnet.
AB  - We present numerical simulation of separating magnetic particles with different
      magnetic susceptibilities by magnetic chromatography using a high-temperature
      superconducting bulk magnet. The transient transport is numerically simulated for
      two kinds of particles having different magnetic susceptibilities. The time
      evolutions were calculated for the particle concentration in the narrow channel
      of the spiral arrangement placed in the magnetic field. The field is produced by
      the highly magnetized high-temperature superconducting bulk magnet. The numerical
      results show the flow velocity difference of the particle transport corresponding
      to the difference in the magnetic susceptibility, as well as the possible
      separation of paramagnetic particles of 20 nm diameter.

PMID- 27877262
TI  - On-chip diamagnetic repulsion in continuous flow.
AB  - We explore the potential of a microfluidic continuous flow particle separation
      system based on the repulsion of diamagnetic materials from a high magnetic
      field. Diamagnetic polystyrene particles in paramagnetic manganese (II) chloride
      solution were pumped into a microfluidic chamber and their deflection behaviour
      in a high magnetic field applied by a superconducting magnet was investigated.
      Two particle sizes (5 and 10 MUm) were examined in two concentrations of MnCl2 (6
      and 10%). The larger particles were repelled to a greater extent than the smaller
      ones, and the effect was greatly enhanced when the particles were suspended in a
      higher concentration of MnCl2. These findings indicate that the system could be
      viable for the separation of materials of differing size and/or diamagnetic
      susceptibility, and as such could be suitable for the separation and sorting of
      small biological species for subsequent studies.

PMID- 27877263
TI  - X-ray diffraction measurements in high magnetic fields and at high temperatures.
AB  - A system was developed measuring x-ray powder diffraction in high magnetic fields
      up to 5 T and at temperatures from 283 to 473 K. The stability of the temperature
      is within 1 K over 6 h. In order to examine the ability of the system, the high
      field x-ray diffraction measurements were carried out for Si and a Ni-based
      ferromagnetic shape-memory alloy. The results show that the x-ray powder
      diffraction measurements in high magnetic fields and at high temperatures are
      useful for materials research.

PMID- 27877264
TI  - Phase selection controlled by sodium ions in the synthesis of FAU/LTA composite
      zeolite.
AB  - Zeolite faujasite (FAU), Linde type A (LTA) and FAU/LTA composite have been
      synthesized using tetramethylammonium cation (TMA+) as template, by adjusting
      only the concentration of Na+ ions in the initial solution (1.00 Al2O3 4.36 SiO2
      : 2.39 (TMA)2 O : beta Na2 O : 249.00H2 O). Na+ ions alter the phase composition
      of the product more than TMA+ or OH- ions. When Na2 O concentration [Na2 O]
      increases from 0.024 to 0.168, the product gradually changes from pure FAU to
      pure LTA via the formation of FAU/LTA composite with increasing LTA fraction.
      Interestingly, the induction periods of FAU and LTA in the FAU/LTA composite
      zeolite ([Na2 O] is 0.072) are both 13 h, quite different from the induction
      periods of their individual pure phases-45 h for FAU and 4 h for LTA. During the
      crystallization, the LTA/(FAU + LTA) fraction in the composite zeolite decreases
      in a nearly linear fashion. Scanning electron microscopy, thermogravimetry and
      differential thermal analysis indicate some difference between the properties of
      the FAU/LTA composite zeolite and of the mechanical mixture.

PMID- 27877265
TI  - Synthesis of polyacrylate/polyethylene glycol interpenetrating network hydrogel
      and its sorption of heavy-metal ions.
AB  - A simple two-step aqueous polymerization method was introduced to synthesize a
      polyacrylate/polyethylene glycol (PAC/PEG) interpenetrating network (IPN)
      hydrogel. On the basis of the effects of the ratio of PAC to PEG, neutralization
      degree, heavy-metal ion concentration, and temperature on the adsorption behavior
      of PAC/PEG IPN hydrogel toward Ni2 +, Cr3 + and Cd2 +, the preparation conditions
      were optimized. In our system, the greatest amount of Ni2 +, Cr3 + and Cd2 +
      adsorbed were 102.34, 49.38 and 33.41 mg g- 1, respectively. The adsorption
      abilities of a dried PAC/PEG composite and a swollen PAC/PEG IPN hydrogel were
      compared. It was found that the efficiency of removing metal ions using the
      swollen hydrogel was greater than that using the dried composite. The adsorption
      mechanism and model are also discussed.

PMID- 27877266
TI  - Enhancement of antibacterial properties of Ag nanorods by electric field.
AB  - The effect of an electric field on the antibacterial activity of columnar aligned
      silver nanorods was investigated. Silver nanorods with a polygonal cross section,
      a width of 20-60 nm and a length of 260-550 nm, were grown on a titanium
      interlayer by applying an electric field perpendicular to the surface of a
      Ag/Ti/Si(100) thin film during its heat treatment at 700  degrees C in an Ar+H2
      environment. The optical absorption spectrum of the silver nanorods exhibited two
      peaks at wavelengths of 350 and 395 nm corresponding to the main surface plasmon
      resonance bands of the one-dimensional silver nanostructures. It was found that
      the silver nanorods with an fcc structure were bounded mainly by {100} facets.
      The antibacterial activity of the silver nanorods against Escherichia coli
      bacteria was evaluated at various electric fields applied in the direction of the
      nanorods without any electrical connection between the nanorods and the capacitor
      plates producing the electric field. Increasing the electric field from 0 to 50 V
      cm-1 resulted in an exponential increase in the relative rate of reduction of the
      bacteria from 3.9*10-2 to 10.5*10-2 min-1. This indicates that the antibacterial
      activity of silver nanorods can be enhanced by applying an electric field, for
      application in medical and food-preserving fields.

PMID- 27877267
TI  - Decomposition of Fe5C2 catalyst particles in carbon nanofibers during TEM
      observation.
AB  - The effect of an electron beam on nanoparticles of two Fe carbide catalysts
      inside a carbon nanofiber was investigated in a transmission electron microscope.
      Electron beam exposure does not result in significant changes for cementite
      (theta-Fe3C). However, for Hagg carbide nanoparticles (chi-Fe5C2), explosive
      decay is observed after exposure for 5-10 s. This produces small particles of
      cementite and gamma-Fe, each covered with a multilayer carbon shell, and
      significantly modifies the carbon-fiber structure. It is considered that the
      decomposition of Hagg carbide is mostly due to the damage induced by high-energy
      electron collisions with the crystal lattice, accompanied by the heating of the
      particle and by mechanical stress provided by the carbon layers of the nanofiber.

PMID- 27877268
TI  - Improved fire retardancy of thermoset composites modified with carbon nanofibers.
AB  - Multifunctional thermoset composites were made from polyester resin, glass fiber
      mats and carbon nanofiber sheets (CNS). Their flaming behavior was investigated
      with cone calorimeter under well-controlled combustion conditions. The heat
      release rate was lowered by pre-planting carbon nanofiber sheets on the sample
      surface with the total fiber content of only 0.38 wt.%. Electron microscopy
      showed that carbon nanofiber sheet was partly burned and charred materials were
      formed on the combusting surface. Both the nanofibers and charred materials acted
      as an excellent insulator and/or mass transport barrier, improving the fire
      retardancy of the composite. This behavior agrees well with the general mechanism
      of fire retardancy in various nanoparticle-thermoplastic composites.

PMID- 27877269
TI  - Characterization of platinum-iron catalysts supported on MCM-41 synthesized with
      rice husk silica and their performance for phenol hydroxylation.
AB  - Mesoporous material RH-MCM-41 was synthesized with rice husk silica by a
      hydrothermal method. It was used as a support for bimetallic platinum-iron
      catalysts Pt-Fe/RH-MCM-41 for phenol hydroxylation. The catalysts were prepared
      by co-impregnation with Pt and Fe at amounts of 0.5 and 5.0 wt.%, respectively.
      The RH-MCM-41 structure in the catalysts was studied with x-ray diffraction, and
      their surface areas were determined by nitrogen adsorption. The oxidation number
      of Fe supported on RH-MCM-41 was + 3, as determined by x-ray absorption near edge
      structure (XANES) analysis. Transmission electron microscopy (TEM) images of all
      the catalysts displayed well-ordered structures, and metal nanoparticles were
      observed in some catalysts. All the catalysts were active for phenol
      hydroxylation using H2O2 as the oxidant at phenol : H2O2 mole ratios of 2 : 1, 2
      : 2, 2 : 3 and 2 : 4. The first three ratios produced only catechol and
      hydroquinone, whereas the 2 : 4 ratio also produced benzoquinone. The 2 : 3 ratio
      gave the highest phenol conversion of 47% at 70  degrees C. The catalyst prepared
      by co-impregnation with Pt and Fe was more active than that prepared using a
      physical mixture of Pt/RH-MCM-41 and Fe/RH-MCM-41.

PMID- 27877270
TI  - High-temperature resistivity and thermoelectric properties of coupled substituted
      Ca3Co2O6.
AB  - Polycrystalline samples of Ca3-x Na x Co2-x Mn x O6 (x=0.0-0.5) have been
      prepared by the sol-gel cum combustion method using sucrose in order to
      investigate the effects of the coupled substitution of Na and Mn on Ca and Co
      sites on the transport properties of Ca3Co2O6(Co326). The products were
      characterized by Fourier transform infrared spectroscopy, powder x-ray
      diffraction (XRD), thermogravimetry (TGA), differential thermal analysis and
      scanning electron microscopy. XRD patterns reveal the formation of single-phase
      products up to x=0.5. Coupled substitution increases the solubility of both Na
      and Mn on Ca and Co sites, respectively, in contrast to the limited solubility of
      Na and Mn (x=0.2) when separately substituted. TGA confirms the formation of the
      Ca3Co2O6 phase at temperatures ~720  degrees C. The grain size of the parent and
      substituted products is in the range 150-250 nm. Electrical resistivity and
      Seebeck coefficient were measured in the temperature range 300-800 K. Resistivity
      shows semiconducting behavior for all the compositions, particularly in the low
      temperature regime. The Seebeck coefficient increases with temperature throughout
      the measured temperature range for all compositions. The maximum Seebeck
      coefficient (200 MUV K-1) is observed for x=0.5 at 825 K, and this composition
      may be optimal for high-temperature thermoelectric applications.

PMID- 27877271
TI  - Mechanical properties of Ti-6Al-4V specimens produced by shaped metal deposition.
AB  - Shaped metal deposition is a novel technique to build near net-shape components
      layer by layer by tungsten inert gas welding. Especially for complex shapes and
      small quantities, this technique can significantly lower the production cost of
      components by reducing the buy-to-fly ratio and lead time for production,
      diminishing final machining and preventing scrap. Tensile testing of Ti-6Al-4V
      components fabricated by shaped metal deposition shows that the mechanical
      properties are competitive to material fabricated by conventional techniques. The
      ultimate tensile strength is between 936 and 1014 MPa, depending on the
      orientation and location. Tensile testing vertical to the deposition layers
      reveals ductility between 14 and 21%, whereas testing parallel to the layers
      gives a ductility between 6 and 11%. Ultimate tensile strength and ductility are
      inversely related. Heat treatment within the alpha+beta phase field does not
      change the mechanical properties, but heat treatment within the beta phase field
      increases the ultimate tensile strength and decreases the ductility. The
      differences in ultimate tensile strength and ductility can be related to the
      alpha lath size and orientation of the elongated, prior beta grains. The micro
      hardness and Young's modulus are similar to conventional Ti-6Al-4V with low
      oxygen content.

PMID- 27877272
TI  - Focus on Organic Conductors.

PMID- 27877273
TI  - Lyotropic liquid crystal directed synthesis of nanostructured materials.
AB  - This review introduces and summarizes lyotropic liquid crystal (LLC) directed
      syntheses of nanostructured materials consisting of porous nanostructures and
      zero-dimensional (0-D), one-dimensional (1-D) and two-dimensional (2-D)
      nanostructures. After a brief introduction to the liquid crystals, the LLCs used
      to prepare mesoporous materials are discussed; in particular, recent advances in
      controlling mesostructures are summarized. The LLC templates directing the
      syntheses of nanoparticles, nanorods, nanowires and nanoplates are also
      presented. Finally, future development in this field is discussed.

PMID- 27877274
TI  - Tetrathiapentalene-based organic conductors.
AB  - The synthesis, structure and properties of tetrathiapentalene-based (TTP) organic
      conductors are reviewed. Among various TTP-type donors, bis-fused
      tetrathiafulvalene, 2,5-bis(1,3-dithiol-2-ylidene)-1,3,4,6-tetrathiapentalene
      (BDT-TTP) and its derivatives afford many metallic radical cation salts stable
      down to low temperatures, regardless of the size and shape of the counter anions.
      Most BDT-TTP conductors have a beta-type donor arrangement with almost uniform
      stacks. Introduction of appropriate substituents results in molecular packing
      that differs from the beta-type. A vinylogous TTP, 2-(1,3-dithiol-2-ylidene)-5-(2
      ethanediylidene-1,3-dithiole)-1,3,4,6-tetrathiapentalene (DTEDT) has yielded an
      organic superconductor (DTEDT)3Au(CN)2 as well as metallic radical cation salts,
      regardless of the counter anions. (Thio)pyran analogs of TTP, namely (T)PDT-TTP
      and its derivatives produce molecular conductors with novel molecular
      arrangements. A TTP analog with reduced pi-electron system 2,5-bis(1,3-dithian-2
      ylidene)-1,3,4,6-tetrathiapentalene (BDA-TTP) has afforded several organic
      superconductors. Highly conducting molecular metals with unusual oxidation states
      (+1, +5/3 and neutral) have been developed on the basis of 2,5-bis(1,3-dithiol-2
      ylidene)-1,3,4,6-tetrathiapentalene (BDT-TTP) derivatives and analogous metal
      derivatives M(dt)2 (M = Ni, Au).

PMID- 27877275
TI  - New aspects of pi-d interactions in magnetic molecular conductors.
AB  - The 2 : 1 cation radical salts of bent donor molecules of ethylenedithio
      tetrathiafulvalenoquinone-1,3-dithiolemethide (EDT-TTFVO), ethylenedithio
      diselenadithiafulvalenoquinone-1,3-dithiolemethide (EDT-DSDTFVO), ethylenedithio
      diselenadithiafulvalenothioquinone-1,3-diselenolemethide (EDT-DSDTFVSDS),
      ethylenedioxy-tetrathiafulvalenoquinone-1,3-dithiolemethide (EDO-TTFVO) and
      ethylenedioxy-tetrathiafulvalenoquinone-1,3-diselenolemethide (EDO-TTFVODS) with
      FeX4- (X = Cl, Br) ions are prepared by electrocrystallization. The crystal
      structures of these salts are composed of alternately stacked donor molecule and
      magnetic anion layers. The band structures of the donor molecule layers are
      calculated using the overlap integrals between neighboring donor molecules and
      are compared with the observed electronic transport properties. The magnetic
      ordering of the Fe(III) d spins of FeX4- ions is determined from magnetization
      and heat capacity measurements. The magnetic ordering temperatures are estimated
      by considering a combination of a direct d-d interaction between the d spins and
      an indirect pi-d interaction between the conduction pi electron and the d spins,
      whose magnitudes are separately calculated from the crystal structures with an
      extended Huckel molecular orbital method. The occurrence of a pi-d interaction is
      proved by the negative magnetoresistance, and the magnitude of magnetoresistance
      reflects the strength of the pi-d interaction. The effect of pressure on the
      magnetoresistance is studied, and the result indicates that the magnitude of
      magnetoresistance increases, namely, the pi-d interaction is enhanced with
      increasing pressure. From these experimental results it is shown that (EDT
      TTFVO)2*FeBr4 is a ferromagnetic semiconductor, (EDT-DSDTFVO)2*FeX4 (X = Cl, Br)
      and (EDT-DSDTFVSDS)2*FeBr4 are metals exhibiting antiferromagnetic ordering of
      the d spins, and (EDO-TTFVO)2*FeCl4 and (EDO-TTFVODS)2*FeBr4*(DCE)0.5 (DCE =
      dichloroethane) are genuine antiferromagnetic metals. Among them, the (EDT
      TTFVO)2*FeBr4 salt is the first pi-d molecular system where the d spins of FeBr4-
      ions are ferromagnetically ordered through antiferromagnetic interaction with the
      conduction pi electrons. Corresponding to this ferromagnetic ordering, an
      anomalous dielectric slow-down phenomenon toward the ordering temperature is
      observed. The pi-d interaction in (EDT-DSDTFVSDS)2*FeBr4 is very large and
      comparable to that in lambda-(BETS)2*FeCl4, which has the highest reported value
      so far, while the d-d interaction is fairly small. Concerning the ratio between
      the magnitudes of pi-d and d-d interactions (Jpid/Jdd), this salt is currently
      the best pi-d molecular system.

PMID- 27877276
TI  - Organic superconductors with an incommensurate anion structure.
AB  - Superconducting incommensurate organic composite crystals based on the
      methylenedithio-tetraselenafulvalene (MDT-TSF) series donors, where the energy
      band filling deviates from the usual 3/4-filled, are reviewed. The incommensurate
      anion potential reconstructs the Fermi surface for both (MDT-TSF)(AuI2)0.436 and
      (MDT-ST)(I3)0.417 neither by the fundamental anion periodicity q nor by 2 q , but
      by 3 q , where MDT-ST is 5H-2-(1,3-dithiol-2-ylidene)-1,3-diselena-4,6
      dithiapentalene, and q is the reciprocal lattice vector of the anion lattice. The
      selection rule of the reconstructing vectors is associated with the magnitude of
      the incommensurate potential. The considerably large interlayer transfer integral
      and three-dimensional superconducting properties are due to the direct donor
      donor interactions coming from the characteristic corrugated conducting sheet
      structure. The materials with high superconducting transition temperature, Tc,
      have large ratios of the observed cyclotron masses to the bare ones, which
      indicates that the strength of the many-body effect is the major determinant of
      Tc. (MDT-TS)(AuI2)0.441 shows a metal-insulator transition at TMI=50 K, where MDT
      TS is 5H-2-(1,3-diselenol-2-ylidene)-1,3,4,6-tetrathiapentalene, and the
      insulating phase is an antiferromagnet with a high Neel temperature (TN=50 K) and
      a high spin-flop field (Bsf=6.9 T). There is a possibility that this material is
      an incommensurate Mott insulator. Hydrostatic pressure suppresses the insulating
      state and induces superconductivity at Tc=3.2 K above 1.05 GPa, where Tc rises to
      the maximum, Tcmax=4.9 K at 1.27 GPa. This compound shows a usual temperature
      pressure phase diagram, in which the superconducting phase borders on the
      antiferromagnetic insulating phase, despite the unusual band filling.

PMID- 27877277
TI  - Variety of valence bond states formed of frustrated spins on triangular lattices
      based on a two-level system Pd(dmit)2.
AB  - Recent studies on the physical properties of the triangular system based on the
      Pd(dmit)2 salts (dmit=1,3-dithiole-2-thione-4,5-dithiolate) are reviewed. Quantum
      chemical architectures of the Pd(dmit)2 molecule and its dimer are introduced
      with emphasis on the strong dimerization of a two-level system, which provides
      unique physical properties of the salts. The magnetic properties are outlined in
      view of the magneto-structural correlation specific to the frustrated spin
      systems. Some newly discovered ground states and their origins are discussed, for
      which the valence bond formation plays a key role. Among them, the two-level
      structure is crucial for the novel charge-separated state found in two salts. The
      valence bond ordering, similar to the spin-Peierls transition, has been found in
      a two-dimensional frustrated spin system. The physical aspects and possible
      relation to the pressure-induced superconductivity are discussed.

PMID- 27877278
TI  - Organic metal (EDO-TTF)2PF6 with multi-instability.
AB  - The multi-instability of the electronic structure of (EDO-TTF)2PF6, where EDO-TTF
      means ethylene-dioxytetrathiafulvalene, is reviewed. This complex showed the
      metal-insulator transition at 280 K associated with distinct molecular
      deformations. The mechanism is interpreted as the cooperation of Peierls
      transition, charge ordering, and the order-disorder transition of the
      countercomponent. The charge ordering pattern in the low-temperature phase is of
      the novel [0, 0, 1, 1] type. The sensitivity of the electronic state to external
      perturbations is demonstrated applying not only static but also instantaneous
      stimuli. In the latter case, the photo-induced phase transition is ultrafast and
      highly efficient. One photon causes the transition of several hundreds of donor
      molecules in the low-temperature phase to relax into a highly conducting
      metastable state within about 1.5 ps. In the early stage of the transient state,
      the charge ordering of the [1, 0, 1, 0] type occurs. As for the chemical
      modifications of this material, the partial deuteration of this complex increases
      the metal-insulator transition temperature. The introduction of a methyl group
      greatly modulates the electronic structure of the complex, i.e. (methyl-EDO
      TTF)2X (X=BF4, ClO4) shows a two-dimensional electronic structure. The working
      hypotheses for developing the systems with multi-instability are described.

PMID- 27877279
TI  - Spatial mapping of electronic states in kappa-(BEDT-TTF)2X using infrared
      reflectivity.
AB  - We review our recent work on spatial inhomogeneity of the electronic states in
      the strongly correlated molecular conductors kappa-(BEDT-TTF)2X. Spatial mapping
      of infrared spectra (SMIS) is used for imaging the distribution of the local
      electronic states. In molecular materials, the infrared response of the specific
      molecular vibration mode with a strong electron-molecular vibration coupling can
      reflect the electronic states via the change in the vibration frequency. By
      spatially mapping the frequency shift of the molecular vibration mode, an
      electronic phase separation has been visualized near the first-order Mott
      transition in the bandwidth-controlled organic conductor kappa-(BEDT
      TTF)2Cu[N(CN)2]Br. In addition to reviewing SMIS of the phase separation, we
      briefly mention the electronic and optical properties of kappa-(BEDT-TTF)2X.

PMID- 27877280
TI  - Recent progress in high-pressure studies on organic conductors.
AB  - Recent high-pressure studies of organic conductors and superconductors are
      reviewed. The discovery of the highest Tc superconductivity among organics under
      high pressure has triggered the further progress of the high-pressure research.
      Owing to this finding, various organic conductors with the strong electron
      correlation were investigated under high pressures. This review includes the
      pressure techniques using the cubic anvil apparatus, as well as high-pressure
      studies of the organic conductors up to 10 GPa showing extraordinary temperature
      and pressure dependent transport phenomena.

PMID- 27877281
TI  - Experimental study of organic zero-gap conductor alpha-(BEDT-TTF)2I3.
AB  - A zero-gap state with a Dirac cone type energy dispersion was discovered in the
      organic conductor alpha-(BEDT-TTF)2I3 under high hydrostatic pressures. This is
      the first two-dimensional (2D) zero-gap state discovered in bulk crystals with a
      layered structure. In contrast to the case of graphene, the Dirac cone in this
      system is highly anisotropic. The present system, therefore, provides a new type
      of massless Dirac fermion system with anisotropic Fermi velocity. This system
      exhibits remarkable transport phenomena characteristic to electrons on the Dirac
      cone type energy structure. The carrier density, written as n?T2, is a
      characteristic feature of the 2D zero-gap structure. On the other hand, the
      resistivity per layer (sheet resistance RS) is given as RS=h/e2 and is
      independent of temperature. The effect of a magnetic field on samples in the zero
      gap system was examined. The difference between zero-gap conductors and
      conventional conductors is the appearance of a Landau level called the zero mode
      at the contact points when a magnetic field is applied normal to the conductive
      layer. Zero-mode Landau carriers give rise to strong negative out-of-plane
      magnetoresistance.

PMID- 27877283
TI  - Magneto-optical studies of low-dimensional organic conductors.
AB  - Our periodic orbit resonance (POR) results on quasi-two-dimensional (q2D), highly
      anisotropic q2D and quasi-one-dimensional (q1D) organic conductors are reviewed
      together with our rotational cavity magneto-optical measurement system. Higher
      order POR up to seventh order has been observed in the q2D system (BEDT
      TTF)2Br(DIA), and the experimental conditions to observe POR and the cyclotron
      resonance (CR) are discussed. Highly anisotropic q2D Fermi surface (FS) in beta"
      (BEDT-TTF)(TCNQ), which was considered to have q1D FS previously, is proposed by
      our POR measurements, and the possible interpretations of other experimental
      results of beta"-(BEDT-TTF)(TCNQ) are discussed assuming the highly anisotropic
      q2D FS. Finally, detailed q1D FS of (DMET)2I3, obtained from our POR results, is
      discussed in connection with the typical q1D system (TMTSF)2ClO4.

PMID- 27877282
TI  - Theoretical study of the zero-gap organic conductor alpha-(BEDT-TTF)2I3.
AB  - The quasi-two-dimensional molecular conductor alpha-(BEDT-TTF)2I3 exhibits
      anomalous transport phenomena where the temperature dependence of resistivity is
      weak but the ratio of the Hall coefficient at 10 K to that at room temperature is
      of the order of 104. These puzzling phenomena were solved by predicting massless
      Dirac fermions, whose motions are described using the tilted Weyl equation with
      anisotropic velocity. alpha-(BEDT-TTF)2I3 is a unique material among several
      materials with Dirac fermions, i.e. graphene, bismuth, and quantum wells such as
      HgTe, from the view-points of both the structure and electronic states described
      as follows. alpha-(BEDT-TTF)2I3 has the layered structure with highly two
      dimensional massless Dirac fermions. The anisotropic velocity and incommensurate
      momenta of the contact points, +/-k0, originate from the inequivalency of the
      BEDT-TTF sites in the unit cell, where +/-k0 moves in the first Brillouin zone
      with increasing pressure. The massless Dirac fermions exist in the presence of
      the charge disproportionation and are robust against the increase in pressure.
      The electron densities on those inequivalent BEDT-TTF sites exhibit anomalous
      momentum distributions, reflecting the angular dependences of the wave functions
      around the contact points. Those unique electronic properties affect the spatial
      oscillations of the electron densities in the vicinity of an impurity. A marked
      behavior of the Hall coefficient, where the sign of the Hall coefficient reverses
      sharply but continuously at low temperatures around 5 K, is investigated by
      treating the interband effects of the magnetic field exactly. It is shown that
      such behavior is possible by assuming the existence of the extremely small amount
      of electron doping. The enhancement of the orbital diamagnetism is also expected.
      The results of the present research shed light on a new aspect of Dirac fermion
      physics, i.e. the emergence of unique electronic properties owing to the
      structure of the material.

PMID- 27877284
TI  - First-principles electronic-band calculations on organic conductors.
AB  - Predicting electronic-band structures is a key issue in understanding the
      properties of materials or in materials design. In this review article,
      application examples of first-principles calculations, which are not based on
      adjustable empirical parameters, to study electronic structures of organic
      conductors are described.

PMID- 27877285
TI  - Theoretical aspects of charge correlations in theta-(BEDT-TTF)2X.
AB  - A review is given on the theoretical studies of charge correlations in theta
      (BEDT-TTF)2X. Various studies show that within a purely electronic model on the
      theta-type lattice with on-site U and nearest neighbor Vp and Vc interactions,
      the diagonal stripe, c-axis three-fold, and the vertical stripe charge
      correlations are favored in the regime Vp <Vc , Vp ~Vc , and Vp >Vc ,
      respectively. In the realistic parameter regime of Vp ~Vc , there is competition
      between the c-axis three fold state and diagonal stripe state. Since these are
      different from the experimentally observed a-axis three fold and the horizontal
      stripe charge correlations, additional effects have to be included in order to
      understand the experiments. The electron-lattice coupling, which tends to distort
      the lattice into the theta d -type, is found to favor the horizontal stripe
      state, suggesting that the occurrence of this stripe ordering in the actual
      materials may not be of purely electronic origin. On the other hand, distant
      electron-electron interactions have to be considered in order to understand the a
      axis three fold correlation, whose wave vector is close to the nesting vector of
      the Fermi surface. These studies seem to suggest that the minimal model to
      understand the charge correlation in theta-(BEDT-TTF)2X may be more complicated
      than expected. Future problems regarding the competition between different types
      of charge correlations are discussed.

PMID- 27877287
TI  - Organic field-effect transistors using single crystals.
AB  - Organic field-effect transistors using small-molecule organic single crystals are
      developed to investigate fundamental aspects of organic thin-film transistors
      that have been widely studied for possible future markets for 'plastic
      electronics'. In reviewing the physics and chemistry of single-crystal organic
      field-effect transistors (SC-OFETs), the nature of intrinsic charge dynamics is
      elucidated for the carriers induced at the single crystal surfaces of molecular
      semiconductors. Materials for SC-OFETs are first reviewed with descriptions of
      the fabrication methods and the field-effect characteristics. In particular, a
      benchmark carrier mobility of 20-40 cm2 Vs-1, achieved with thin platelets of
      rubrene single crystals, demonstrates the significance of the SC-OFETs and
      clarifies material limitations for organic devices. In the latter part of this
      review, we discuss the physics of microscopic charge transport by using SC-OFETs
      at metal/semiconductor contacts and along semiconductor/insulator interfaces.
      Most importantly, Hall effect and electron spin resonance (ESR) measurements
      reveal that interface charge transport in molecular semiconductors is properly
      described in terms of band transport and localization by charge traps.

PMID- 27877288
TI  - Assembly and electroanalytical performance of Prussian blue/polypyrrole composite
      nanoparticles synthesized by the reverse micelle method.
AB  - We report on the characterization, assembly and electroanalytical performance of
      Prussian blue/polypyrrole (PBPPy) composite nanoparticles synthesized by the
      reverse micelle method. Scanning electron microscopy suggests the formation of
      nanosized PBPPy particles with diameters between 40 and 50 nm. Optical absorption
      confirms that the particles are composed of Prussian blue (PB) and polypyrrole.
      PB and PBPPy nanoparticles were anchored onto the surface of cysteine-modified Au
      electrodes. Cyclic voltammetry experiments show that PB- or PBPPy-modified
      electrodes exhibit intrinsic electrochemical properties and a high
      electrocatalytic activity towards H2O2. PBPPy-modified electrodes exhibit a
      higher sensitivity to H2O2 than PB-modified electrodes. A linear calibration
      curve in the concentration range 0.99 MUM-8.26 mM H2O2 is constructed with a
      detection limit of 0.23 MUM at a signal-to-noise ratio of 3. Excellent stability
      is observed for PBPPy-composite-nanoparticle-modified electrodes even in a pH 6
      phosphate buffer solution with a high H2O2 concentration (0.99 mM).
      Glutaraldehyde and [Formula: see text] were also employed to immobilize glucose
      oxidase for the development of PBPPy-based biosensors. The results show that
      PBPPy composite nanoparticles can be used to develop oxidase-based biosensors.

PMID- 27877286
TI  - Organic semiconductors for organic field-effect transistors.
AB  - The advantages of organic field-effect transistors (OFETs), such as low cost,
      flexibility and large-area fabrication, have recently attracted much attention
      due to their electronic applications. Practical transistors require high
      mobility, large on/off ratio, low threshold voltage and high stability.
      Development of new organic semiconductors is key to achieving these parameters.
      Recently, organic semiconductors have been synthesized showing comparable
      mobilities to amorphous-silicon-based FETs. These materials make OFETs more
      attractive and their applications have been attempted. New organic semiconductors
      resulting in high-performance FET devices are described here and the relationship
      between transistor characteristics and chemical structure is discussed.

PMID- 27877289
TI  - Simple preparation of silica and alumina with a hierarchical pore system via the
      dual-templating method.
AB  - Silica and alumina with macro-meso-type hierarchical pore systems are synthesized
      by dual templating using both surfactants and polystyrene (PS) spheres. After
      calcination, scanning electron microscope images show uniform macropores with a
      diameter of approximately 200 nm. This size coincides with that of the original
      PS spheres. The density of the macropores increases with the amount of added PS
      spheres in the precursor solutions. Transmission electron microscope images,
      small-angle x-ray scattering spectra and N2 adsorption-desorption isotherms
      reveal the formation of ordered mesoporous structures in the macropore walls.
      Also, the existence of micropores (less than 2 nm in size) was confirmed from the
      large N2 uptake at low relative pressures.

PMID- 27877290
TI  - Porous hydroxyapatite and biphasic calcium phosphate ceramics promote ectopic
      osteoblast differentiation from mesenchymal stem cells.
AB  - Because calcium phosphate (Ca-P) ceramics have been used as bone substitutes, it
      is necessary to investigate what effects the ceramics have on osteoblast
      maturation. We prepared three types of Ca-P ceramics with different Ca-P ratios,
      i.e. hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP), and biphasic
      calcium phosphate (BCP) ceramics with dense-smooth and porous structures.
      Comprehensive gene expression microarray analysis of mouse osteoblast-like cells
      cultured on these ceramics revealed that porous Ca-P ceramics considerably
      affected the gene expression profiles, having a higher potential for osteoblast
      maturation. In the in vivo study that followed, porous Ca-P ceramics were
      implanted into rat skeletal muscle. Sixteen weeks after the implantation, more
      alkaline-phosphatase-positive cells were observed in the pores of hydroxyapatite
      and BCP, and the expression of the osteocalcin gene (an osteoblast-specific
      marker) in tissue grown in pores was also higher in hydroxyapatite and BCP than
      in beta-TCP. In the pores of any Ca-P ceramics, 16 weeks after the implantation,
      we detected the expressions of marker genes of the early differentiation stage of
      chondrocytes and the complete differentiation stage of adipocytes, which
      originate from mesenchymal stem cells, as well as osteoblasts. These marker gene
      expressions were not observed in the muscle tissue surrounding the implanted Ca-P
      ceramics. These observations indicate that porous hydroxyapatite and BCP had a
      greater potential for promoting the differentiation of mesenchymal stem cells
      into osteoblasts than beta-TCP.

PMID- 27877291
TI  - Effect of starting powders on the sintering of nanostructured ZrO2 ceramics by
      colloidal processing.
AB  - The effect of starting powders on the sintering of nanostructured tetragonal
      zirconia was evaluated. Suspensions were prepared with a concentration of 10
      vol.% by mixing a bicomponent mixture of commercial powders (97 mol.% monoclinic
      zirconia with 3 mol.% yttria) and by dispersing commercially available tetragonal
      zirconia (3YTZ, Tosoh). The preparation of the slurry by bead-milling was
      optimized. Colloidal processing using 50 MUm zirconia beads at 4000 rpm generated
      a fully deagglomerated suspension leading to the formation of high-density
      consolidated compacts (62% of the theoretical density (TD) for the bicomponent
      suspension). Optimum colloidal processing of the bicomponent suspension followed
      by the sintering of yttria and zirconia allowed us to obtain nanostructured
      tetragonal zirconia. Three different sintering techniques were investigated:
      normal sintering, two-step sintering and spark plasma sintering. The inhibition
      of grain growth in the bicomponent mixed powders in comparison with 3YTZ was
      demonstrated. The inhibition of the grain growth may have been caused by inter
      diffusion of cations during the sintering.

PMID- 27877292
TI  - Aerosol-assisted synthesis of mesoporous organosilica microspheres with
      controlled organic contents.
AB  - Periodic mesoporous organosilica (PMO) spherical particles with different organic
      contents were synthesized in one pot by reacting 1,2-bis(triethoxysilyl)ethane
      (BTSE) with tetraethylorthosilicate (TEOS) using a spray-drying technique. The
      scanning electron microscopy observation of spray-dried products clearly showed
      the formation of spherical particles. The 29Si magic angle spinning nuclear
      magnetic resonance data revealed that the organic contents due to ethane
      fragments embedded in the frameworks were controllable and consistent with the
      BTSE/TEOS molar ratios of precursor solutions. Transmission electron microscopy,
      small-angle x-ray scattering, and N2 adsorption data of PMO with controlled
      organic contents indicated that the ethane fragments were embedded in the
      frameworks with the formation of ordered mesostructures. PMO with a high organic
      content (BTSE/TEOS=0.50) only showed a hydrophobic property. According to the
      same procedure, benzene groups were also integrated to a similar degree in the
      frameworks by using 1,4-bis(triethoxysilyl)benzene.

PMID- 27877293
TI  - Focus on Novel Nanoelectromechanical 3D Structures: Fabrication and Properties.

PMID- 27877294
TI  - Nanoelectromechanical device fabrications by 3-D nanotechnology using focused-ion
      beams.
AB  - Nanoelectromechanical devices, which can be used as nanotools in nanofactories,
      were fabricated by focused ion beam chemical vapor deposition (FIB-CVD). The
      devices are made of diamond-like carbon (DLC), deposited on a Si substrate using
      gasified phenanthrene (C14H10) as a carbon source. The Young modulus and density
      of the deposited DLC were measured as 190 GPa and 3.8 g cm-3, respectively. The
      work function was smaller for DLC (2.9 eV) than for W (4.7 eV) and Fe (5.2 eV)
      deposited by FIB-CVD. A nanomanipulator was manufactured by FIB-CVD and used for
      actual manipulations. A glass capillary based local field emitter was developed
      and produced as a tool for spot deposition, and its electron field emission was
      confirmed. FIB-CVD is proven as an efficient fabrication technology of novel
      nanoelectromechanical devices.

PMID- 27877295
TI  - 3D heterostructures and systems for novel MEMS/NEMS.
AB  - In this review, we consider the application of solid micro- and nanostructures of
      various shapes as building blocks for micro-electro-mechanical or nano-electro
      mechanical systems (MEMS/NEMS). We provide examples of practical applications of
      structures created by MEMS/NEMS fabrication. Novel devices are briefly described,
      such as a high-power electrostatic nanoactuator, a fast-response tubular
      anemometer for measuring gas and liquid flows, a nanoprinter, a nanosyringe and
      optical MEMS/NEMS. The prospects are described for achieving NEMS with tunable
      quantum properties.

PMID- 27877296
TI  - High-frequency micromechanical columnar resonators.
AB  - High-frequency silicon columnar microresonators are fabricated using a simple but
      effective technological scheme. An optimized fabrication scheme was invented to
      obtain mechanically protected microcolumns with lateral dimensions controlled on
      a scale of at least 1 MUm. In this paper, we investigate the influence of the
      environmental conditions on the mechanical resonator properties. At ambient
      conditions, we observed a frequency stability deltaf/f of less than 10-6 during 5
      h of operation at almost constant temperature. However, varying the temperature
      shifts the frequency by approximately -173 Hz  degrees C- 1. In accordance with a
      viscous damping model of the ambient gas, we perceived that the quality factor of
      the first flexural mode decreased with the inverse of the square root of
      pressure. However, in the low-pressure regime, a linear dependence was observed.
      We also investigated the influence of the type of the immersing gas on the
      resonant frequency.

PMID- 27877297
TI  - Manganese oxide nanoparticle-assisted laser desorption/ionization mass
      spectrometry for medical applications.
AB  - We prepared and characterized manganese oxide magnetic nanoparticles (d =5.6 nm)
      and developed nanoparticle-assited laser desorption/ionization (nano-PALDI) mass
      spectrometry. The nanoparticles had MnO2 and Mn2O3 cores conjugated with hydroxyl
      and amino groups, and showed paramagnetism at room temperature. The nanoparticles
      worked as an ionization assisting reagent in mass spectroscopy. The mass spectra
      showed no background in the low m/z. The nanoparticles could ionize samples of
      peptide, drug and proteins (approx. 5000 Da) without using matrix, i.e., 2,5
      dihydroxybenzoic acid (DHB), 4-hydroxy-alpha-cinnamic acid (CHCA) and liquid
      matrix, as conventional ionization assisting reagents. Post source decay spectra
      by nano-PALDI mass spectrometry will yield information of the chemical structure
      of analytes.

PMID- 27877298
TI  - SNP genotyping by DNA photoligation: application to SNP detection of genes from
      food crops.
AB  - We describe a simple and inexpensive single-nucleotide polymorphism (SNP) typing
      method, using DNA photoligation with 5-carboxyvinyl-2'-deoxyuridine and two
      fluorophores. This SNP-typing method facilitates qualitative determination of
      genes from indica and japonica rice, and showed a high degree of single
      nucleotide specificity up to 10 000. This method can be used in the SNP typing of
      actual genomic DNA samples from food crops.

PMID- 27877299
TI  - Immunochromatographic assay using gold nanoparticles for measuring salivary
      secretory IgA in dogs as a stress marker.
AB  - The concentration of salivary secretory immunoglobulin A (sIgA) is a well-known
      stress marker for humans. The concentration of salivary sIgA in dogs has also
      been reported as a useful stress marker. In addition, salivary sIgA in dogs has
      been used to determine the adaptive ability of dogs for further training. There
      are conventional procedures based on enzyme-linked immunosorbent assay (ELISA)
      for measuring salivary sIgA in dogs. However, ELISA requires long assay time,
      complicated operations and is costly. In the present study, we developed an
      immunochromatographic assay for measuring salivary sIgA in dogs using a dilution
      buffer containing a non-ionic surfactant. We determined 2500-fold dilution as the
      optimum condition for dog saliva using a phosphate buffer (50 mM, pH 7.2)
      containing non-ionic surfactant (3 wt% Tween 20). The results obtained from the
      saliva samples of three dogs using immunochromatographic assay were compared with
      those obtained from ELISA. It was found that the immunochromatographic assay is
      applicable to judge the change in salivary sIgA in each dog. The
      immunochromatographic assay for salivary sIgA in dogs is a promising tool, which
      should soon become commercially available for predicting a dog's psychological
      condition and estimating adaptive ability for training as guide or police dogs.

PMID- 27877300
TI  - Sugar microarray via click chemistry: molecular recognition with lectins and
      amyloid beta (1-42).
AB  - Sugar microarrays were fabricated on various substrates via click chemistry.
      Acetylene-terminated substrates were prepared by forming self-assembled
      monolayers (SAMs) on a gold substrate with alkyl-disulfide and on silicon, quartz
      and glass substrates with a silane-coupling reagent. The gold substrates were
      subjected to surface plasmon resonance measurements, and the quartz and glass
      substrates were subjected to spectroscopy measurements and optical microscopy
      observation. The saccharide-immobilized substrate on the gold substrate showed
      specific interaction with the corresponding lectin, and the saccharides showed
      inert surface properties to other proteins with a high signal-to-noise ratio. We
      also focused on the saccharide-protein interaction on protein amyloidosis of
      Alzheimer amyloid beta. Amyloid beta peptide showed conformation transition on
      the saccharide-immobilization substrate into a beta-sheet, and fibril formation
      and amyloid aggregates were found on the specific saccharides.

PMID- 27877301
TI  - An electrochemical sensing platform based on a new copper complex for the
      determination of hydrogen peroxide and nitrite.
AB  - A new copper(II) complex [Cu(C12H23N3)4Br2.2H2O] was synthesized and its
      structure was characterized by x-ray crystallography and elemental analysis. The
      copper atom had a distorted octahedron coordination involving two bromide anions
      and four nitrogen atoms from the 1-decyl-1H-[1,2,4]triazole ligands. Moreover,
      the electrochemical behavior and electrocatalysis of the carbon paste electrode
      (Cu-CPE) bulk-modified by the complex have been studied in detail. The Cu-CPE
      showed excellent electrocatalytic activities toward the reduction of hydrogen
      peroxide and nitrite, and the detection limit was much lower than that mentioned
      in earlier reports. This bulk-modified CPE has good reproducibility, long-term
      stability and surface renewability, which appear promising for constructing
      chemical sensors.

PMID- 27877302
TI  - Preparation and properties of antibacterial TiO2@C/Ag core-shell composite.
AB  - An environment-friendly hydrothermal method was used to prepare TiO2@C core-shell
      composite using TiO2 as core and sucrose as carbon source. TiO2@C served as a
      support for the immobilization of Ag by impregnation in silver nitrate aqueous
      solution. The chemical structures and morphologies of TiO2@C and TiO2@C/Ag
      composite were characterized by x-ray diffraction, transmission electron
      microscopy, Fourier transform infrared spectroscopy, energy dispersive x-ray
      spectroscopy and Brunauer-Emmett-Teller (BET) analysis. The antibacterial
      properties of the TiO2@C/Ag core-shell composite against Escherichia coli (E.
      coli) and Staphylococcus aureus (S. aureus) were examined by the viable cell
      counting method. The results indicate that silver supported on the surface of
      TiO2@C shows excellent antibacterial activity.

PMID- 27877303
TI  - ZnO films grown by pulsed-laser deposition on soda lime glass substrates for the
      ultraviolet inactivation of Staphylococcus epidermidis biofilms.
AB  - We found that a ZnO film of 2 MUm thickness which was laser-deposited at room
      temperature onto a plain soda lime glass substrate, exhibits notable
      antibacterial activity against a biofilm of Staphylococcus epidermidis when back
      illuminated by a UVA light source with a peak emission wavelength of about 365
      nm. X-ray diffraction (XRD), scanning electron microscopy (SEM), atomic force
      microscopy (AFM), UV-visible absorption spectroscopy, Raman spectroscopy and x
      ray photoemission spectroscopy (XPS) were used to characterize the ZnO films
      before and after the interactions with the biofilm and the ultraviolet light,
      respectively. The as-deposited film was highly textured with the wurtzite (0002)
      in-plane orientation (c-axis perpendicular to ZnO surface) and had a surface rms
      roughness of 49.7 nm. In the as-deposited film, the Zn to O ratio was 1 to 0.95.
      After the UV and biofilm treatments, the ZnO film surface had become rougher (rms
      roughness 68.1 nm) and presented uniform micron-sized pitting randomly
      distributed, while the zinc to oxygen ratio had become 1 to 2.2. In this case,
      both the UV-visible and Raman spectra pointed to degradation of the structural
      quality of the material. On the strength of these data, we propose a model for
      the mediation of the bactericidal activity in which the photogeneration of highly
      oxidizing species and the presence of active surface defect sites both play an
      important role. This study is of particular interest for the acute problem of
      disinfection of pathogenic biofilms which form on medical device/implant
      surfaces.

PMID- 27877304
TI  - Inherent tensile strength of molybdenum nanocrystals.
AB  - The strength of Mo nanorods was measured under uniaxial tension. Tensile tests of
      < 110>-oriented single-crystalline molybdenum rod-shaped specimens with diameters
      from 25 to 90 nm at the apex were conducted inside a field-ion microscope (FIM).
      The nanocrystals were free from dislocations, planar defects and microcracks, and
      exhibited the plastic mode of failure under uniaxial tension with the formation
      of a chisel-edge tip by multiple gliding in the [Formula: see text] and [Formula:
      see text] deformation systems. The experimental values of tensile strength vary
      between 6.3 and 19.8 GPa and show a decrease with increasing nanorod diameter. A
      molecular dynamic simulation of Mo nanorod tension also suggests that the
      strength decreases from 28.8 to 21.0 GPa when the rod diameter increases from 3.1
      to 15.7 nm. The maximum values of experimental strength are thought to correspond
      to the inherent strength of Mo nanocrystals under uniaxial tension (19.8 GPa, or
      7.5% of Young's modulus).

PMID- 27877305
TI  - Formation of molecular doping patterns in organic-inorganic hybrid films by a
      capillary electrophoresis doping technique.
AB  - A new technique is proposed for the fabrication of fine patterns of molecular
      doping in organic-inorganic hybrid materials by the combination of capillary
      electrophoresis doping (CED) and photolithography. The UV-induced polymerization
      of [Formula: see text] bonds in organic groups yields a fine contrast of
      structures with the desired pattern in organic-inorganic hybrid films, and CED
      treatment introduces functional molecules only into unirradiated regions to form
      the doping patterns of molecules inside the films. The fine patterning of
      rhodamine-6G doping with from 2 to 4 MUm resolution is demonstrated in hybrid
      films of 10 MUm thickness.

PMID- 27877306
TI  - Water vapor effect on high-temperature oxidation behavior of Fe3Al
      intermetallics.
AB  - Fe3Al intermetallics (Fe3Al, Fe3Al-Zr, Fe3Al-Zr,Mo and Fe3Al-Zr, Mo, Nb) were
      oxidized at 950  degrees C in dry and humid (11 vol% water) synthetic air.
      Thermogravimetric measurements showed that the oxidation rates of the tested
      intermetallics were lower in humid air than in dry air (especially for Fe3Al-Zr,
      Mo and Fe3Al-Zr, Mo, Nb). The addition of small amounts of Zr, Mo or Nb improved
      the kinetics compared with that of the undoped Fe3Al. Fe3Al showed massive
      spallation, whereas Fe3Al-Zr, Fe3Al-Zr, Mo and Fe3Al-Zr, Mo, Nb produced a flat,
      adherent oxide layer. The rapid transformation of transient alumina into alpha
      alumina may explain the decrease in the oxidation rate in humid air.

PMID- 27877307
TI  - Characterization of the uncertainties in the constitutive behavior of carbon
      nanotube/cement composites.
AB  - This paper addresses the uncertainties associated with using carbon nanotubes
      (CNTs) as reinforcement for cement. These uncertainties emerge mainly from the
      CNTs' wide range of mechanical properties and their interfacial behavior with
      cement. This study sheds light on the basis of choosing the optimal combinations
      of CNTs mechanical and interfacial parameters to improve the structural strength
      and ductility of CNT-reinforced cementitious composites. The finite element
      method (FEM) is employed to study the individual and interactive effects of five
      parameters, including interfacial shear (bond) strength, allowable slip, CNT
      Young's modulus, residual bond stress and aspect ratio. Numerical results show
      that the parameters, at certain ranges of values, interact substantially and
      greatly alter the mechanical properties of the composite. It is also found that
      the governing parameter is the CNT Young's modulus, which determines whether the
      composite is ductility critical or strength critical. Furthermore, the level of
      residual bond stress substantially influences the effect of other parameters,
      especially in the case of composite ductility.

PMID- 27877308
TI  - Electric current activated/assisted sintering (ECAS): a review of patents 1906
      2008.
AB  - The electric current activated/assisted sintering (ECAS) is an ever growing class
      of versatile techniques for sintering particulate materials. Despite the
      tremendous advances over the last two decades in ECASed materials and products
      there is a lack of comprehensive reviews on ECAS apparatuses and methods. This
      paper fills the gap by tracing the progress of ECAS technology from 1906 to 2008
      and surveys 642 ECAS patents published over more than a century. It is found that
      the ECAS technology was pioneered by Bloxam (1906 GB Patent No. 9020) who
      developed the first resistive sintering apparatus. The patents were searched by
      keywords or by cross-links and were withdrawn from the Japanese Patent Office
      (342 patents), the United States Patent and Trademark Office (175 patents), the
      Chinese State Intellectual Property Office of P.R.C. (69 patents) and the World
      Intellectual Property Organization (12 patents). A subset of 119 (out of 642)
      ECAS patents on methods and apparatuses was selected and described in detail with
      respect to their fundamental concepts, physical principles and importance in
      either present ECAS apparatuses or future ECAS technologies for enhancing
      efficiency, reliability, repeatability, controllability and productivity. The
      paper is divided into two parts, the first deals with the basic concepts,
      features and definitions of basic ECAS and the second analyzes the auxiliary
      devices/peripherals. The basic ECAS is classified with reference to discharge
      time (fast and ultrafast ECAS). The fundamental principles and definitions of
      ECAS are outlined in accordance with the scientific and patent literature.

PMID- 27877309
TI  - Engineering a light-emitting planar defect within three-dimensional photonic
      crystals.
AB  - Sandwich structures, constructed from a planar defect of rhodamine-B (RhB)-doped
      titania (TiO2) and two photonic crystals, were synthesized via the self-assembly
      method combined with spin-coating. The modification of the spontaneous emission
      of RhB molecules in such structures was investigated experimentally. The
      spontaneous emission of RhB-doped TiO2 film with photonic crystals was reduced by
      a factor of 5.5 over a large bandwidth of 13% of the first-order Bragg
      diffraction frequency when compared with that of RhB-doped TiO2 film without
      photonic crystals. The angular dependence of the modification and the
      photoluminescence lifetime of RhB molecules demonstrate that the strong and wide
      suppression of the spontaneous emission of the RhB molecules is due to the
      presence of the photonic band gap.

PMID- 27877310
TI  - Theory of electrostatics and electrokinetics of soft particles.
AB  - We investigate theoretically the electrostatics and electrokinetics of a soft
      particle, i.e. a hard particle covered with an ion-penetrable surface layer of
      polyelectrolytes. The electric properties of soft particles in an electrolyte
      solution, which differ from those of hard particles, are essentially determined
      by the Donnan potential in the surface layer. In particular, the Donnan potential
      plays an essential role in the electrostatics and electrokinetics of soft
      particles. Furthermore, the concept of zeta potential, which is important in the
      electrokinetics of hard particles, loses its physical meaning in the
      electrokinetics of soft particles. In this review, we discuss the potential
      distribution around a soft particle, the electrostatic interaction between two
      soft particles, and the motion of a soft particle in an electric field.

PMID- 27877311
TI  - Fabrication and characteristics of porous germanium films.
AB  - Porous germanium films with good adhesion to the substrate were produced by
      annealing GeO2 ceramic films in H2 atmosphere. The reduction of GeO2 started at
      the top of a film and resulted in a Ge layer with a highly porous surface. TEM
      and Raman measurements reveal small Ge crystallites at the top layer and a higher
      degree of crystallinity at the bottom part of the Ge film; visible
      photoluminescence was detected from the small crystallites. Porous Ge films
      exhibit high density of holes (1020 cm-3) and a maximum of Hall mobility at ~225
      K. Their p-type conductivity is dominated by the defect scattering mechanism.

PMID- 27877312
TI  - Carbon nanocones: wall structure and morphology.
AB  - Large-scale production of conical carbon nanostructures is possible through
      pyrolysis of hydrocarbons in a plasma torch process. The resulting carbon cones
      occur in five distinctly different forms, and disc-shaped particles are produced
      as well. The structure and properties of these carbon cones and discs have been
      relatively little explored until now. Here we characterize the structure of these
      particles using transmission electron microscopy, synchrotron x-ray and electron
      diffraction. The carbon nanocones are found to exhibit several interesting
      structural features; instead of having a uniform cross-section, the walls consist
      of a relatively thin inner graphite-like layer with a non-crystalline envelope,
      where the amount of the latter can be modified significantly by annealing. The
      cones appear with a well-defined faceting along the cone edge, demonstrating
      strict long-range atomic ordering; they also present occasional examples of
      symmetry breaking, such as two apexes appearing in the same carbon nanocone.

PMID- 27877313
TI  - STAM celebrates its 10th anniversary.

PMID- 27877314
TI  - Focus on nanobiomaterials and technologies for breakthrough in future medicine.

PMID- 27877315
TI  - Global gene expression analysis for evaluation and design of biomaterials.
AB  - Comprehensive gene expression analysis using DNA microarrays has become a
      widespread technique in molecular biological research. In the biomaterials field,
      it is used to evaluate the biocompatibility or cellular toxicity of metals,
      polymers and ceramics. Studies in this field have extracted differentially
      expressed genes in the context of differences in cellular responses among
      multiple materials. Based on these genes, the effects of materials on cells at
      the molecular level have been examined. Expression data ranging from several to
      tens of thousands of genes can be obtained from DNA microarrays. For this reason,
      several tens or hundreds of differentially expressed genes are often present in
      different materials. In this review, we outline the principles of DNA
      microarrays, and provide an introduction to methods of extracting information
      which is useful for evaluating and designing biomaterials from comprehensive gene
      expression data.

PMID- 27877316
TI  - Immobilization of biomolecules on the surface of inorganic nanoparticles for
      biomedical applications.
AB  - Various inorganic nanoparticles have been used for drug delivery, magnetic
      resonance and fluorescence imaging, and cell targeting owing to their unique
      properties, such as large surface area and efficient contrasting effect. In this
      review, we focus on the surface functionalization of inorganic nanoparticles via
      immobilization of biomolecules and the corresponding surface interactions with
      biocomponents. Applications of surface-modified inorganic nanoparticles in
      biomedical fields are also outlined.

PMID- 27877318
TI  - Preparation of novel bioactive nano-calcium phosphate-hydrogel composites.
AB  - Nano-sized hydroxyapatite (nHA) and carbonate-substituted hydroxyapatite (nCHA)
      particles were incorporated into a poly-2
      hydroxyethylmethacrylate/polycaprolactone (PHEMA/PCL) hydrogel at a filler
      content of 10 wt%. Fourier transform infrared absorption, transmission electron
      microscopy, x-ray diffraction and scanning electron microscopy were used to
      analyse the physical and chemical characteristics of the calcium phosphate
      fillers and resultant composites. Nano-sized calcium phosphate particles were
      produced with a needle-like morphology, average length of 50 nm and an aspect
      ratio of 3. The nanoparticles were uniformly distributed in the polymer matrix.
      The addition of both HA and CHA in nano-form enhanced the bioactivity and
      biocompatibility of the PHEMA/PCL matrix. The carbonate-substitution has allowed
      for improved bioactivity and biocompatibility of the resultant composite,
      indicating the potential of this material for use in bone tissue engineering.

PMID- 27877317
TI  - Cell and biomolecule delivery for regenerative medicine.
AB  - Regenerative medicine is an exciting field that aims to create regenerative
      alternatives to harvest tissues for transplantation. In this approach, the
      delivery of cells and biological molecules plays a central role. The scaffold
      (synthetic temporary extracellular matrix) delivers cells to the regenerative
      site and provides three-dimensional environments for the cells. To fulfil these
      functions, we design biodegradable polymer scaffolds with structural features on
      multiple size scales. To enhance positive cell-material interactions, we design
      nano-sized structural features in the scaffolds to mimic the natural
      extracellular matrix. We also integrate micro-sized pore networks to facilitate
      mass transport and neo tissue regeneration. We also design novel polymer devices
      and self-assembled nanospheres for biomolecule delivery to recapitulate key
      events in developmental and wound healing processes. Herein, we present recent
      work in biomedical polymer synthesis, novel processing techniques, surface
      engineering and biologic delivery. Examples of enhanced cellular/tissue function
      and regenerative outcomes of these approaches are discussed to demonstrate the
      excitement of the biomimetic scaffold design and biologic delivery in
      regenerative medicine.

PMID- 27877320
TI  - Nickel-free austenitic stainless steels for medical applications.
AB  - The adverse effects of nickel ions being released into the human body have
      prompted the development of high-nitrogen nickel-free austenitic stainless steels
      for medical applications. Nitrogen not only replaces nickel for austenitic
      structure stability but also much improves steel properties. Here we review the
      harmful effects associated with nickel in medical stainless steels, the
      advantages of nitrogen in stainless steels, and emphatically, the development of
      high-nitrogen nickel-free stainless steels for medical applications. By combining
      the benefits of stable austenitic structure, high strength and good plasticity,
      better corrosion and wear resistances, and superior biocompatibility compared to
      the currently used 316L stainless steel, the newly developed high-nitrogen nickel
      free stainless steel is a reliable substitute for the conventional medical
      stainless steels.

PMID- 27877319
TI  - Biopolymeric nanoparticles.
AB  - This review on nanoparticles highlights the various biopolymers (proteins and
      polysaccharides) which have recently revolutionized the world of biocompatible
      and degradable natural biological materials. The methods of their fabrication,
      including emulsification, desolvation, coacervation and electrospray drying are
      described. The characterization of different parameters for a given nanoparticle,
      such as particle size, surface charge, morphology, stability, structure, cellular
      uptake, cytotoxicity, drug loading and drug release, is outlined together with
      the relevant measurement techniques. Applications in the fields of medicine and
      biotechnology are discussed along with a promising future scope.

PMID- 27877321
TI  - Artificial extracellular matrix for embryonic stem cell cultures: a new frontier
      of nanobiomaterials.
AB  - Nanobiomaterials can play a central role in regenerative medicine and tissue
      engineering by facilitating cellular behavior and function, such as those where
      extracellular matrices (ECMs) direct embryonic stem (ES) cell morphogenesis,
      proliferation, differentiation and apoptosis. However, controlling ES cell
      proliferation and differentiation using matrices from natural sources is still
      challenging due to complex and heterogeneous culture conditions. Moreover, the
      systemic investigation of the regulation of self-renewal and differentiation to
      lineage specific cells depends on the use of defined and stress-free culture
      conditions. Both goals can be achieved by the development of biomaterial design
      targeting ECM or growth factors for ES cell culture. This targeted application
      will benefit from expansion of ES cells for transplantation, as well as the
      production of a specific differentiated cell type either by controlling the
      differentiation in a very specific pathway or by elimination of undesirable cell
      types.

PMID- 27877322
TI  - Conducting polymer-hydrogels for medical electrode applications.
AB  - Conducting polymers hold significant promise as electrode coatings; however, they
      are characterized by inherently poor mechanical properties. Blending or producing
      layered conducting polymers with other polymer forms, such as hydrogels, has been
      proposed as an approach to improving these properties. There are many challenges
      to producing hybrid polymers incorporating conducting polymers and hydrogels,
      including the fabrication of structures based on two such dissimilar materials
      and evaluation of the properties of the resulting structures. Although both
      fabrication and evaluation of structure-property relationships remain challenges,
      materials comprised of conducting polymers and hydrogels are promising for the
      next generation of bioactive electrode coatings.

PMID- 27877323
TI  - Electrospun nanofibrous materials for tissue engineering and drug delivery.
AB  - The electrospinning technique, which was invented about 100 years ago, has
      attracted more attention in recent years due to its possible biomedical
      applications. Electrospun fibers with high surface area to volume ratio and
      structures mimicking extracellular matrix (ECM) have shown great potential in
      tissue engineering and drug delivery. In order to develop electrospun fibers for
      these applications, different biocompatible materials have been used to fabricate
      fibers with different structures and morphologies, such as single fibers with
      different composition and structures (blending and core-shell composite fibers)
      and fiber assemblies (fiber bundles, membranes and scaffolds). This review
      summarizes the electrospinning techniques which control the composition and
      structures of the nanofibrous materials. It also outlines possible applications
      of these fibrous materials in skin, blood vessels, nervous system and bone tissue
      engineering, as well as in drug delivery.

PMID- 27877325
TI  - Stem cell technology using bioceramics: hard tissue regeneration towards clinical
      application.
AB  - Mesenchymal stem cells (MSCs) are adult stem cells which show differentiation
      capabilities toward various cell lineages. We have already used MSCs for
      treatments of osteoarthritis, bone necrosis and bone tumor. For this purpose,
      culture expanded MSCs were combined with various ceramics and then implanted.
      Because of rejection response to allogeneic MSC implantation, we have utilized
      patients' own MSCs for the treatment. Bone marrow is a good cell source of MSCs,
      although the MSCs also exist in adipose tissue. When comparing osteogenic
      differentiation of these MSCs, bone marrow MSCs show more extensive bone forming
      capability than adipose MSCs. Thus, the bone marrow MSCs are useful for bone
      tissue regeneration. However, the MSCs show limited proliferation and
      differentiation capabilities that hindered clinical applications in some cases.
      Recent advances reveal that transduction of plural transcription factors into
      human adult cells results in generation of new type of stem cells called induced
      pluripotent stem cells (iPS cells). A drawback of the iPS cells for clinical
      applications is tumor formation after their in vivo implantation; therefore it is
      difficult to use iPS cells for the treatment. To circumvent the problem, we
      transduced a single factor of either SOX2 or NANOG into the MSCs and found high
      proliferation as well as osteogenic differentiation capabilities of the MSCs. The
      stem cells could be combined with bioceramics for clinical applications. Here, we
      summarize our recent technologies using adult stem cells in viewpoints of bone
      tissue regeneration.

PMID- 27877324
TI  - Multifunctional nanoassemblies of block copolymers for future cancer therapy.
AB  - Nanoassemblies from amphiphilic block copolymers are promising nanomedicine
      platforms for cancer diagnosis and therapy due to their relatively small size,
      high loading capacity of drugs, controlled drug release, in vivo stability and
      prolonged blood circulation. Recent clinical trials with self-assembled polymeric
      micelles incorporating anticancer drugs have shown improved antitumor activity
      and decreased side effects encouraging the further development of nanoassemblies
      for drug delivery. This review summarizes recent approaches considering stimuli
      responsive, multifunctionality and more advanced architectures, such as vesicles
      or worm-like micelles, for tumor-specific drug and gene delivery.

PMID- 27877327
TI  - Trend report on international and Japanese standardization activities for
      bioceramics and tissue engineered medical products.
AB  - Since porous and injectable bioceramics have recently been utilized often as
      scaffolds for bone regenerative medicine, the need for their standardization has
      increased. One of the standard proposals in ISO/TC150 and JIS has been a draft
      for characterization of the porous bioceramic scaffolds in both micro- and macro
      scopic aspects. ISO/TC150/SC7 (Tissue engineered medical products) has been co
      chaired by Professor J E Lemons, Department of Surgery, University of Alabama at
      Birmingham and Dr R Nakaoka, Division of Medical Devices, National Institute of
      Health Sciences, Japan. The scope of SC7 has been specified as 'Standardization
      for the general requirements and performance of tissue engineered medical
      products with the exclusion of gene therapy, transplantation and transfusion'.

PMID- 27877326
TI  - Fabrication of a thermoresponsive cell culture dish: a key technology for cell
      sheet tissue engineering.
AB  - This article reviews the properties and characterization of an intelligent
      thermoresponsive surface, which is a key technology for cell sheet-based tissue
      engineering. Intelligent thermoresponsive surfaces grafted with poly(N
      isopropylacrylamide) exhibit hydrophilic/hydrophobic alteration in response to
      temperature change. Cultured cells are harvested on thermoresponsive cell culture
      dishes by decreasing the temperature without the use of digestive enzymes or
      chelating agents. Our group has developed cell sheet-based tissue engineering for
      therapeutic uses with single layer or multilayered cell sheets, which were
      recovered from the thermoresponsive cell culture dish. Using surface derivation
      techniques, we developed a new generation of thermoresponsive cell culture dishes
      to improve culture conditions. We also designed a new methodology for
      constructing well-defined organs using microfabrication techniques.

PMID- 27877329
TI  - Spatially resolved positron annihilation spectroscopy on friction stir weld
      induced defects.
AB  - A friction stir welded (FSW) Al alloy sample was investigated by Doppler
      broadening spectroscopy (DBS) of the positron annihilation line. The spatially
      resolved defect distribution showed that the material in the joint zone becomes
      completely annealed during the welding process at the shoulder of the FSW tool,
      whereas at the tip, annealing is prevailed by the deterioration of the material
      due to the tool movement. This might be responsible for the increased probability
      of cracking in the heat affected zone of friction stir welds. Examination of a
      material pairing of steel S235 and the Al alloy Silafont36 by coincident Doppler
      broadening spectroscopy (CDBS) indicates the formation of annealed steel clusters
      in the Al alloy component of the sample. The clear visibility of Fe in the CDB
      spectra is explained by the very efficient trapping at the interface between
      steel cluster and bulk.

PMID- 27877328
TI  - Raman effect in icosahedral boron-rich solids.
AB  - We present Raman spectra of numerous icosahedral boron-rich solids having the
      structure of alpha-rhombohedral, beta-rhombohedral, alpha-tetragonal, beta
      tetragonal, YB66, orthorhombic or amorphous boron. The spectra were newly
      measured and, in some cases, compared with reported data and discussed. We
      emphasize the importance of a high signal-to-noise ratio in the Raman spectra for
      detecting weak effects evoked by the modification of compounds, accommodation of
      interstitial atoms and other structural defects. Vibrations of the icosahedra,
      occurring in all the spectra, are interpreted using the description of modes in
      alpha-rhombohedral boron by Beckel et al. The Raman spectrum of boron carbide is
      largely clarified. Relative intra- and inter-icosahedral bonding forces are
      estimated for the different structural groups and for vanadium-doped beta
      rhombohedral boron. The validity of Badger's rule is demonstrated for the force
      constants of inter-icosahedral B-B bonds, whereas the agreement is less
      satisfactory for the intra-icosahedral B-B bonds.

PMID- 27877331
TI  - Nanomechanical properties of silicon surfaces nanostructured by excimer laser.
AB  - Excimer laser irradiation at ambient temperature has been employed to produce
      nanostructured silicon surfaces. Nanoindentation was used to investigate the
      nanomechanical properties of the deformed surfaces as a function of laser
      parameters, such as the angle of incidence and number of laser pulses at a fixed
      laser fluence of 5 J cm-2. A single-crystal silicon [311] surface was severely
      damaged by laser irradiation and became nanocrystalline with an enhanced
      porosity. The resulting laser-treated surface consisted of nanometer-sized
      particles. The pore size was controlled by adjusting the angle of incidence and
      the number of laser pulses, and varied from nanometers to microns. The extent of
      nanocrystallinity was large for the surfaces irradiated at a small angle of
      incidence and by a high number of pulses, as confirmed by x-ray diffraction and
      Raman spectroscopy. The angle of incidence had a stronger effect on the structure
      and nanomechanical properties than the number of laser pulses.

PMID- 27877330
TI  - Structural analysis of anodic porous alumina used for resistive random access
      memory.
AB  - Anodic porous alumina with duplex layers exhibits a voltage-induced switching
      effect and is a promising candidate for resistive random access memory. The
      nanostructural analysis of porous alumina is important for understanding the
      switching effect. We investigated the difference between the two layers of an
      anodic porous alumina film using transmission electron microscopy and electron
      energy-loss spectroscopy. Diffraction patterns showed that both layers are
      amorphous, and the electron energy-loss spectroscopy indicated that the inner
      layer contains less oxygen than the outer layer. We speculate that the conduction
      paths are mostly located in the oxygen-depleted area.

PMID- 27877332
TI  - Yield stress of duplex stainless steel specimens estimated using a compound Hall
      Petch equation.
AB  - In this study, the 0.2% yield stress of duplex stainless steel was evaluated
      using a compound Hall-Petch equation. The compound Hall-Petch equation was
      derived from four types of duplex stainless steel, which contained 0.2-64.4 wt%
      delta-ferrite phase, had different chemical compositions and were annealed at
      different temperatures. Intragranular yield stress was measured with an ultra
      microhardness tester and evaluated with the yield stress model proposed by Dao et
      al. Grain size, volume fraction and texture were monitored by electron
      backscattering diffraction measurement. The kgamma constant in the compound
      equation for duplex stainless steel agrees well with that for gamma-phase SUS316L
      steel in the temperature range of 1323-1473 K. The derived compound Hall-Petch
      equation predicts that the yield stress will be in good agreement with the
      experimental results for the Cr, Mn, Si, Ni and N solid-solution states. We find
      that the intragranular yield stress of the delta-phase of duplex stainless steel
      is rather sensitive to the chemical composition and annealing conditions, which
      is attributed to the size misfit parameter.

PMID- 27877333
TI  - Hydrogen embrittlement property of a 1700-MPa-class ultrahigh-strength tempered
      martensitic steel.
AB  - The hydrogen embrittlement property of a prototype 1700-MPa-class ultrahigh
      strength steel (NIMS17) containing hydrogen traps was evaluated using a slow
      strain rate test (SSRT) after cathodic hydrogen precharging, cyclic corrosion
      test (CCT) and atmospheric exposure. The hydrogen content in a fractured specimen
      was measured after SSRT by thermal desorption spectroscopy (TDS). The
      relationship between fracture stress and hydrogen content for the hydrogen
      precharged specimens showed that the fracture stress of NIMS17 steel was higher,
      at a given hydrogen content, than that of conventional AISI 4135 steels with
      tensile strengths of 1300 and 1500 MPa. This suggests better resistance of NIMS17
      steel to hydrogen embrittlement. However, hydrogen uptake to NIMS17 steel under
      CCT and atmospheric exposure decreased the fracture stress. This is because of
      the stronger hydrogen uptake to the steel containing hydrogen traps than to the
      AISI 4135 steels. Although NIMS17 steel has a higher strength level than AISI
      4135 steel with a tensile strength of 1500 MPa, the decrease in fracture stress
      is similar between these steels.

PMID- 27877334
TI  - Synthesis, characterization and swelling properties of guar gum-g-poly(sodium
      acrylate-co-styrene)/muscovite superabsorbent composites.
AB  - A series of novel guar gum-g-poly(sodium acrylate-co-styrene)/muscovite (GG-g
      P(NaA-co-St)/MVT) superabsorbent composites were prepared by free-radical
      grafting copolymerization of natural guar gum (GG), partially neutralized acrylic
      acid (NaA), styrene (St) and muscovite (MVT) using ammonium persulfate (APS) as
      the initiator and N,N-methylene-bis-acrylamide (MBA) as the crosslinker. Optical
      absorption spectra confirmed that NaA and St had been grafted onto the GG main
      chain and MVT participated in the polymerization reaction. The simultaneous
      introduction of St and MVT into the GG-g-PNaA matrix could clearly improve the
      surface morphologies of the composites, and MVT led to better dispersion in the
      polymeric matrix without agglomeration, as revealed by electron microscopy. The
      effects of St and MVT on the water absorption and swelling behavior in various
      saline solutions, aqueous solutions of hydrophilic organic solvents and
      surfactant solutions were investigated. Results indicated that the swelling rate
      and capabilities of the composites were markedly enhanced by the incorporation of
      the hydrophobic monomer St and inorganic MVT clay mineral. The superabsorbent
      composite showed a clearer deswelling characteristic in solutions of multivalent
      saline, acetone and ethanol, and cationic surfactant than that in the solutions
      of multivalent saline, methanol and anionic surfactant.

PMID- 27877336
TI  - Large-area fabrication of superhydrophobic surfaces for practical applications:
      an overview.
AB  - This review summarizes the key topics in the field of large-area fabrication of
      superhydrophobic surfaces, concentrating on substrates that have been used in
      commercial applications. Practical approaches to superhydrophobic surface
      construction and hydrophobization are discussed. Applications of superhydrophobic
      surfaces are described and future trends in superhydrophobic surfaces are
      predicted.

PMID- 27877337
TI  - Water distribution at solid/liquid interfaces visualized by frequency modulation
      atomic force microscopy.
AB  - Interfacial phenomena at solid/water interfaces play an important role in a wide
      range of industrial technologies and biological processes. However, it has been a
      great challenge to directly probe the molecular-scale behavior of water at
      solid/water interfaces. Recently, there have been tremendous advancements in
      frequency modulation atomic force microscopy (FM-AFM), enabling its operation in
      liquids with atomic resolution. The high spatial and force resolutions of FM-AFM
      have enabled the visualization of one-dimensional (1D) profiles of the hydration
      force, two-dimensional (2D) images of hydration layers and three-dimensional (3D)
      images of the water distribution at solid/water interfaces. Here I present an
      overview of the recent advances in FM-AFM instrumentation and its applications to
      the study of solid/water interfaces.

PMID- 27877338
TI  - In vitro formation and thermal transition of novel hybrid fibrils from type I
      fish scale collagen and type I porcine collagen.
AB  - Novel type I collagen hybrid fibrils were fabricated by neutralizing a mixture of
      type I fish scale collagen solution and type I porcine collagen solution with a
      phosphate buffer saline at 28  degrees C. Their structure was discussed in terms
      of the volume ratio of fish/porcine collagen solution. Scanning electron and
      atomic force micrographs showed that the diameter of collagen fibrils derived
      from the collagen mixture was larger than those derived from each collagen, and
      all resultant fibrils exhibited a typical D-periodic unit of ~67 nm, irrespective
      of volume ratio of both collagens. Differential scanning calorimetry revealed
      only one endothermic peak for the fibrils derived from collagen mixture or from
      each collagen solution, indicating that the resultant collagen fibrils were
      hybrids of type I fish scale collagen and type I porcine collagen.

PMID- 27877335
TI  - Field-effect detection using phospholipid membranes.
AB  - The application of field-effect devices to biosensors has become an area of
      intense research interest. An attractive feature of field-effect sensing is that
      the binding or reaction of biomolecules can be directly detected from a change in
      electrical signals. The integration of such field-effect devices into cell
      membrane mimics may lead to the development of biosensors useful in clinical and
      biotechnological applications. This review summarizes recent studies on the
      fabrication and characterization of field-effect devices incorporating model
      membranes. The incorporation of black lipid membranes and supported lipid
      monolayers and bilayers into semiconductor devices is described.

PMID- 27877340
TI  - Focus on innovation in ceramics research in East Asia.

PMID- 27877339
TI  - Synthesis of Y2O2S:Eu3+, Mg2+, Ti4+ hollow microspheres via homogeneous
      precipitation route.
AB  - A phosphorescent material in the form of Y2O2S:Eu3+, Mg2+, Ti4+ hollow
      microspheres was prepared by homogeneous precipitation using monodispersed carbon
      spheres as hard templates. Y2O3:Eu3+ hollow microspheres were first synthesized
      to serve as the precursor. Y2O2S:Eu3+, Mg2+, Ti4+ powders were obtained by
      calcinating the precursor in a CS2 atmosphere. The crystal structure, morphology
      and optical properties of the composites were characterized. X-ray diffraction
      measurements confirmed the purity of the Y2O2S phase. Electron microscopy
      observations revealed that the Y2O2S:Eu3+, Mg2+, Ti4+ particles inherited the
      hollow spherical shape from the precursor after being calcined in a CS2
      atmosphere and that they had a diameter of 350-450 nm and a wall thickness of
      about 50-80 nm. After ultraviolet radiation at 265 or 325 nm for 5 min, the
      particles emitted strong red long-lifetime phosphorescence originating from Eu3+
      ions. This phosphorescence is associated with the trapping of charge carriers by
      Ti4+ and Mg2+ ions.

PMID- 27877342
TI  - Electrode materials: a challenge for the exploitation of protonic solid oxide
      fuel cells.
AB  - High temperature proton conductor (HTPC) oxides are attracting extensive
      attention as electrolyte materials alternative to oxygen-ion conductors for use
      in solid oxide fuel cells (SOFCs) operating at intermediate temperatures (400-700
      degrees C). The need to lower the operating temperature is dictated by cost
      reduction for SOFC pervasive use. The major stake for the deployment of this
      technology is the availability of electrodes able to limit polarization losses at
      the reduced operation temperature. This review aims to comprehensively describe
      the state-of-the-art anode and cathode materials that have so far been tested
      with HTPC oxide electrolytes, offering guidelines and possible strategies to
      speed up the development of protonic SOFCs.

PMID- 27877341
TI  - Low-energy cathodoluminescence microscopy for the characterization of
      nanostructures.
AB  - Spatially and spectrally resolved low-energy cathodoluminescence (CL) microscopy
      was applied to the characterization of nanostructures. CL has the advantage of
      revealing not only the presence of luminescence centers but also their spatial
      distribution. The use of electrons as an excitation source allows a direct
      comparison with other electron-beam techniques. Thus, CL is a powerful method to
      correlate luminescence with the sample structure and to clarify the origin of the
      luminescence. However, caution is needed in the quantitative analysis of CL
      measurements. In this review, the advantages of cathodoluminescence for
      qualitative analysis and disadvantages for quantitative analysis are presented on
      the example of nanostructures.

PMID- 27877343
TI  - Progress in engineering high strain lead-free piezoelectric ceramics.
AB  - Environmental concerns are strongly driving the need to replace the lead-based
      piezoelectric materials currently employed as multilayer actuators. The current
      review describes both compositional and structural engineering approaches to
      achieve enhanced piezoelectric properties in lead-free materials. The review of
      the compositional engineering approach focuses on compositional tuning of the
      properties and phase behavior in three promising families of lead-free perovskite
      ferroelectrics: the titanate, alkaline niobate and bismuth perovskites and their
      solid solutions. The 'structural engineering' approaches focus instead on
      optimization of microstructural features including grain size, grain orientation
      or texture, ferroelectric domain size and electrical bias field as potential
      paths to induce large piezoelectric properties in lead-free piezoceramics. It is
      suggested that a combination of both compositional and novel structural
      engineering approaches will be required in order to realize viable lead-free
      alternatives to current lead-based materials for piezoelectric actuator
      applications.

PMID- 27877344
TI  - Processing of polysiloxane-derived porous ceramics: a review.
AB  - Because of the unique combination of their attractive properties, porous ceramics
      are considered as candidate materials for several engineering applications. The
      production of porous ceramics from polysiloxane precursors offers advantages in
      terms of simple processing methodology, low processing cost, and easy control
      over porosity and other properties of the resultant ceramics. Therefore,
      considerable research has been conducted to produce various Si(O)C-based ceramics
      from polysiloxane precursors by employing different processing strategies. The
      complete potential of these materials can only be achieved when properties are
      tailored for a specific application, whereas the control over these properties is
      highly dependent on the processing route. This review deals with processing
      strategies of polysiloxane-derived porous ceramics. The essential features of
      processing strategies-replica, sacrificial template, direct foaming and reaction
      techniques-are explained and the available literature reports are thoroughly
      reviewed with particular regard to the critical issues that affect pore
      characteristics. A short note on the cross-linking methods of polysiloxanes is
      also provided. The potential of each processing strategy on porosity and strength
      of the resultant SiC or SiOC ceramics is outlined.

PMID- 27877345
TI  - Surface modification and characterization for dispersion stability of inorganic
      nanometer-scaled particles in liquid media.
AB  - Inorganic nanoparticles are indispensable for science and technology as
      materials, pigments and cosmetics products. Improving the dispersion stability of
      nanoparticles in various liquids is essential for those applications. In this
      review, we discuss why it is difficult to control the stability of nanoparticles
      in liquids. We also overview the role of surface interaction between
      nanoparticles in their dispersion and characterization, e.g. by colloid probe
      atomic force microscopy (CP-AFM). Two types of surface modification concepts,
      post-synthesis and in situ modification, were investigated in many previous
      studies. Here, we focus on post-synthesis modification using adsorption of
      various kinds of polymer dispersants and surfactants on the particle surface, as
      well as surface chemical reactions of silane coupling agents. We discuss CP-AFM
      as a technique to analyze the surface interaction between nanoparticles and the
      effect of surface modification on the nanoparticle dispersion in liquids.

PMID- 27877346
TI  - Present status of amorphous In-Ga-Zn-O thin-film transistors.
AB  - The present status and recent research results on amorphous oxide semiconductors
      (AOSs) and their thin-film transistors (TFTs) are reviewed. AOSs represented by
      amorphous In-Ga-Zn-O (a-IGZO) are expected to be the channel material of TFTs in
      next-generation flat-panel displays because a-IGZO TFTs satisfy almost all the
      requirements for organic light-emitting-diode displays, large and fast liquid
      crystal and three-dimensional (3D) displays, which cannot be satisfied using
      conventional silicon and organic TFTs. The major insights of this review are
      summarized as follows. (i) Most device issues, such as uniformity, long-term
      stability against bias stress and TFT performance, are solved for a-IGZO TFTs.
      (ii) A sixth-generation (6G) process is demonstrated for 32" and 37" displays.
      (iii) An 8G sputtering apparatus and a sputtering target have been developed.
      (iv) The important effect of deep subgap states on illumination instability is
      revealed. (v) Illumination instability under negative bias has been intensively
      studied, and some mechanisms are proposed. (vi) Degradation mechanisms are
      classified into back-channel effects, the creation of traps at an interface and
      in the gate insulator, and the creation of donor states in annealed a-IGZO TFTs
      by the Joule heating; the creation of bulk defects should also be considered in
      the case of unannealed a-IGZO TFTs. (vii) Dense passivation layers improve the
      stability and photoresponse and are necessary for practical applications. (viii)
      Sufficient knowledge of electronic structures and electron transport in a-IGZO
      has been accumulated to construct device simulation models.

PMID- 27877347
TI  - Development of novel thermoelectric materials by reduction of lattice thermal
      conductivity.
AB  - Thermal conductivity is one of the key parameters in the figure of merit of
      thermoelectric materials. Over the past decade, most progress in thermoelectric
      materials has been made by reducing their thermal conductivity while preserving
      their electrical properties. The phonon scattering mechanisms involved in these
      strategies are reviewed here and divided into three groups, including (i)
      disorder or distortion of unit cells, (ii) resonant scattering by localized
      rattling atoms and (iii) interface scattering. In addition, we propose
      construction of a 'natural superlattice' in thermoelectric materials by
      intercalating an MX layer into the van der Waals gap of a layered TX2 structure
      which has a general formula of (MX)1+x (TX2) n (M=Pb, Bi, Sn, Sb or a rare earth
      element; T=Ti, V, Cr, Nb or Ta; X=S or Se and n=1, 2, 3). We demonstrate that one
      of the intercalation compounds (SnS)1.2(TiS2)2 has better thermoelectric
      properties compared with pure TiS2 in the direction parallel to the layers, as
      the electron mobility is maintained while the phonon transport is significantly
      suppressed owing to the reduction in the transverse phonon velocities.

PMID- 27877348
TI  - Synthesis and characterization of Eu3+, Ti4+ @ ZnO organosols and nanocrystalline
      c-ZnTiO3 thin films aiming at high transparency and luminescence.
AB  - By exploiting colloidal properties, such as transparency, rheology and versatile
      chemistry, we propose to synthesize new photonic nanomaterials based on colloidal
      solutions and thin films. This contribution highlights our efforts to elaborate
      and to characterize nanostructures based on the ZnO-TiO2 system. Using a recently
      developed sol-gel route to synthesize new Ti4+@ZnO organosols, we were able to
      prepare, at relatively low temperature (400  degrees C) and short annealing time
      (15 min), highly transparent, luminescent, nanocrystalline Eu3+ doped c-ZnTiO3
      thin films. The organosols and thin films were characterized with UV-visible-near
      infrared absorption, ellipsometry, photoluminescence spectroscopy, dynamic light
      scattering, x-ray diffraction and scanning electron microscopy.

PMID- 27877349
TI  - Characterization of Bi and Fe co-doped PZT capacitors for FeRAM.
AB  - Ferroelectric random access memory (FeRAM) has been in mass production for over
      15 years. Higher polarization ferroelectric materials are needed for future
      devices which can operate above about 100  degrees C. With this goal in mind, co
      doping of thin Pb(Zr40,Ti60)O3 (PZT) films with 1 at.% Bi and 1 at.% Fe was
      examined in order to enhance the ferroelectric properties as well as characterize
      the doped material. The XRD patterns of PZT-5% BiFeO3 (BF) and PZT 140-nm thick
      films showed (111) orientation on (111) platinized Si wafers and a 30  degrees C
      increase in the tetragonal to cubic phase transition temperature, often called
      the Curie temperature, from 350 to 380  degrees C with co-doping, indicating that
      Bi and Fe are substituting into the PZT lattice. Raman spectra revealed decreased
      band intensity with Bi and Fe co-doping of PZT compared to PZT. Polarization
      hysteresis loops show similar values of remanent polarization, but square-shaped
      voltage pulse-measured net polarization values of PZT-BF were higher and showed
      higher endurance to repeated cycling up to 1010 cycles. It is proposed that Bi
      and Fe are both in the +3 oxidation state and substituting into the perovskite A
      and B sites, respectively. Substitution of Bi and Fe into the PZT lattice likely
      creates defect dipoles, which increase the net polarization when measured by the
      short voltage pulse positive-up-negative-down (PUND) method.

PMID- 27877350
TI  - Theoretical investigation of methane adsorption onto boron nitride and carbon
      nanotubes.
AB  - Methane adsorption onto single-wall boron nitride nanotubes (BNNTs) and carbon
      nanotubes (CNTs) was studied using the density functional theory within the
      generalized gradient approximation. The structural optimization of several
      bonding configurations for a CH4 molecule approaching the outer surface of the
      (8,0) BNNT and (8,0) CNT shows that the CH4 molecule is preferentially adsorbed
      onto the CNT with a binding energy of -2.84 kcal mol-1. A comparative study of
      nanotubes with different diameters (curvatures) reveals that the methane
      adsorptive capability for the exterior surface increases for wider CNTs and
      decreases for wider BNNTs. The introduction of defects in the BNNT significantly
      enhances methane adsorption. We also examined the possibility of binding a
      bilayer or a single layer of methane molecules and found that methane molecules
      preferentially adsorb as a single layer onto either BNNTs or CNTs. However,
      bilayer adsorption is feasible for CNTs and defective BNNTs and requires binding
      energies of -3.00 and -1.44 kcal mol-1 per adsorbed CH4 molecule, respectively.
      Our first-principles findings indicate that BNNTs might be an unsuitable material
      for natural gas storage.

PMID- 27877351
TI  - Reusable hydroxyapatite nanocrystal sensors for protein adsorption.
AB  - The repeatability of the adsorption and removal of fibrinogen and fetal bovine
      serum on hydroxyapatite (HAp) nanocrystal sensors was investigated by Fourier
      transform infrared (FTIR) spectroscopy and quartz crystal microbalance with
      dissipation (QCM-D) monitoring technique. The HAp nanocrystals were coated on a
      gold-coated quartz sensor by electrophoretic deposition. Proteins adsorbed on the
      HAp sensors were removed by (i) ammonia/hydrogen peroxide mixture (APM), (ii)
      ultraviolet light (UV), (iii) UV/APM, (iv) APM/UV and (v) sodium dodecyl sulfate
      (SDS) treatments. FTIR spectra of the reused surfaces revealed that the APM and
      SDS treatments left peptide fragments or the proteins adsorbed on the surfaces,
      whereas the other methods successfully removed the proteins. The QCM-D
      measurements indicated that in the removal treatments, fibrinogen was slowly
      adsorbed in the first cycle because of the change in surface wettability revealed
      by contact angle measurements. The SDS treatment was not effective in removing
      proteins. The APM or UV treatment decreased the frequency shifts for the reused
      HAp sensors. The UV/APM treatment did not induce the frequency shifts but
      decreased the dissipation shifts. Therefore, we conclude that the APM/UV
      treatment is the most useful method for reproducing protein adsorption behavior
      on HAp sensors.

PMID- 27877352
TI  - Synthesis of monodisperse spherical core-shell SiO2-SrAl2Si2O8: Eu2+ phosphors by
      hydrothermal homogeneous precipitation method.
AB  - Nanocrystalline SrAl2Si2O8 :Eu2+ phosphor layers were coated on nonaggregated,
      monodisperse and spherical SiO2 particles using a hydrothermal homogeneous
      precipitation. After annealing at 1100  degrees C, core-shell SiO2@SrAl2Si2O8
      :Eu2+ particles were obtained. They were characterized with x-ray diffraction
      (XRD), scanning electron microscopy, transmission electron microscopy and
      photoluminescence techniques. XRD analysis confirmed the formation of SiO2
      @SrAl2Si2O8 :Eu2+ particles; it indicated that the SrAl2Si2O8 :Eu2+ shells on
      SiO2 particles consisted of hexagonal crystallites. The core-shell phosphors
      obtained are well-dispersed submicron spherical particles with a narrow size
      distribution. The thickness of the coated layer is approximately 20-40 nm. Under
      ultraviolet excitation (361 nm), the particles emit blue light at about 440 nm
      due to the Eu2+ ions in their shells.

PMID- 27877353
TI  - Continuous production of flexible carbon nanotube-based transparent conductive
      films.
AB  - This work shows a simple, single-stage, scalable method for the continuous
      production of high-quality carbon nanotube-polymer transparent conductive films
      from carbon feedstock. Besides the ease of scalability, a particular advantage of
      this process is that the concentration of nanotubes in the films, and thus
      transparency and conductivity, can be adjusted by changing simple process
      parameters. Therefore, films can be readily prepared for any application desired,
      ranging from solar cells to flat panel displays. Our best results show a surface
      resistivity of the order of 300 Omega square-1 for a film with 80% transparency,
      which is promising at this early stage of process development.

PMID- 27877354
TI  - A methodology to investigate the intrinsic effect of the pulsed electric current
      during the spark plasma sintering of electrically conductive powders.
AB  - A novel methodology is proposed for investigating the effect of the pulsed
      electric current during the spark plasma sintering (SPS) of electrically
      conductive powders without potential misinterpretation of experimental results.
      First, ensemble configurations (geometry, size and material of the powder sample,
      die, plunger and spacers) are identified where the electric current is forced to
      flow only through either the sample or the die, so that the sample is heated
      either through the Joule effect or by thermal conduction, respectively. These
      ensemble configurations are selected using a recently proposed mathematical model
      of an SPS apparatus, which, once suitably modified, makes it possible to carry
      out detailed electrical and thermal analysis. Next, SPS experiments are conducted
      using the ensemble configurations theoretically identified. Using aluminum
      powders as a case study, we find that the temporal profiles of sample shrinkage,
      which indicate densification behavior, as well as the final density of the sample
      are clearly different when the electric current flows only through the sample or
      through the die containing it, whereas the temperature cycle and mechanical load
      are the same in both cases.

PMID- 27877355
TI  - Degradation studies of transparent conductive electrodes on electroactive
      poly(vinylidene fluoride) for uric acid measurements.
AB  - Biochemical analysis of physiological fluids using, for example, lab-on-a-chip
      devices requires accurate mixing of two or more fluids. This mixing can be
      assisted by acoustic microagitation using a piezoelectric material, such as the
      beta-phase of poly(vinylidene fluoride) (beta-PVDF). If the analysis is performed
      using optical absorption spectroscopy and beta-PVDF is located in the optical
      path, the material and its conductive electrodes must be transparent. Moreover,
      if, to improve the transmission of the ultrasonic waves to the fluids, the
      piezoelectric transducer is placed inside the fluidic structures, its degradation
      must be assessed. In this paper, we report on the degradation properties of
      transparent conductive oxides, namely, indium tin oxide (ITO) and aluminum-doped
      zinc oxide, when they are used as electrodes for providing acoustic
      microagitation. The latter promotes mixing of chemicals involved in the
      measurement of uric acid concentration in physiological fluids. The results are
      compared with those for aluminum electrodes. We find that beta-PVDF samples with
      ITO electrodes do not degrade either with or without acoustic microagitation.

PMID- 27877356
TI  - Focus on Advanced Nanomaterials.

PMID- 27877357
TI  - Nanomaterials science.

PMID- 27877358
TI  - Recent developments in inorganically filled carbon nanotubes: successes and
      challenges.
AB  - Carbon nanotubes (CNTs) are a unique class of nanomaterials that can be imagined
      as rolled graphene sheets. The inner hollow of a CNT provides an extremely small,
      one-dimensional space for storage of materials. In the last decade, enormous
      effort has been spent to produce filled CNTs that combine the properties of both
      the host CNT and the guest filling material. CNTs filled with various inorganic
      materials such as metals, alloys, semiconductors and insulators have been
      obtained using different synthesis approaches including capillary filling and
      chemical vapor deposition. Recently, several potential applications have emerged
      for these materials, such as the measurement of temperature at the nanoscale,
      nano-spot welding, and the storage and delivery of extremely small quantities of
      materials. A clear distinction between this class of materials and other
      nanostructures is the existence of an enormous interfacial area between the CNT
      and the filling matter. Theoretical investigations have shown that the lattice
      mismatch and strong exchange interaction of CNTs with the guest material across
      the interface should result in reordering of the guest crystal structure and
      passivation of the surface dangling bonds and thus yielding new and interesting
      physical properties. Despite preliminary successes, there remain many challenges
      in realizing applications of CNTs filled with inorganic materials, such as a
      comprehensive understanding of their growth and physical properties and control
      of their structural parameters. In this article, we overview research on filled
      CNT nanomaterials with special emphasis on recent progress and key achievements.
      We also discuss the future scope and the key challenges emerging out of a decade
      of intensive research on these fascinating materials.

PMID- 27877359
TI  - A study of the synthetic methods and properties of graphenes.
AB  - Graphenes with varying number of layers can be synthesized by using different
      strategies. Thus, single-layer graphene is prepared by micromechanical cleavage,
      reduction of single-layer graphene oxide, chemical vapor deposition and other
      methods. Few-layer graphenes are synthesized by conversion of nanodiamond, arc
      discharge of graphite and other methods. In this article, we briefly overview the
      various synthetic methods and the surface, magnetic and electrical properties of
      the produced graphenes. Few-layer graphenes exhibit ferromagnetic features along
      with antiferromagnetic properties, independent of the method of preparation.
      Aside from the data on electrical conductivity of graphenes and graphene-polymer
      composites, we also present the field-effect transistor characteristics of
      graphenes. Only single-layer reduced graphene oxide exhibits ambipolar
      properties. The interaction of electron donor and acceptor molecules with few
      layer graphene samples is examined in detail.

PMID- 27877360
TI  - Ionic conductivity in oxide heterostructures: the role of interfaces.
AB  - Rapidly growing attention is being directed to the investigation of ionic
      conductivity in oxide film heterostructures. The main reason for this interest
      arises from interfacial phenomena in these heterostructures and their
      applications. Recent results revealed that heterophase interfaces have faster
      ionic conduction pathways than the bulk or homophase interfaces. This finding can
      open attractive opportunities in the field of micro-ionic devices. The influence
      of the interfaces on the conduction properties of heterostructures is becoming
      increasingly important with the miniaturization of solid-state devices, which
      leads to an enhanced interface density at the expense of the bulk. This review
      aims to describe the main evidence of interfacial phenomena in ion-conducting
      film heterostructures, highlighting the fundamental and technological relevance
      and offering guidelines to understanding the interface conduction mechanisms in
      these structures.

PMID- 27877361
TI  - Electronic states of graphene nanoribbons and analytical solutions.
AB  - Graphene is a one-atom-thick layer of graphite, where low-energy electronic
      states are described by the massless Dirac fermion. The orientation of the
      graphene edge determines the energy spectrum of pi-electrons. For example, zigzag
      edges possess localized edge states with energies close to the Fermi level. In
      this review, we investigate nanoscale effects on the physical properties of
      graphene nanoribbons and clarify the role of edge boundaries. We also provide
      analytical solutions for electronic dispersion and the corresponding wavefunction
      in graphene nanoribbons with their detailed derivation using wave mechanics based
      on the tight-binding model. The energy band structures of armchair nanoribbons
      can be obtained by making the transverse wavenumber discrete, in accordance with
      the edge boundary condition, as in the case of carbon nanotubes. However, zigzag
      nanoribbons are not analogous to carbon nanotubes, because in zigzag nanoribbons
      the transverse wavenumber depends not only on the ribbon width but also on the
      longitudinal wavenumber. The quantization rule of electronic conductance as well
      as the magnetic instability of edge states due to the electron-electron
      interaction are briefly discussed.

PMID- 27877362
TI  - Engineering of poly(ethylene glycol) chain-tethered surfaces to obtain high
      performance bionanoparticles.
AB  - A poly(ethylene glycol)-b-poly[2-(N,N-dimethylamino)ethyl methacrylate] block
      copolymer possessing a reactive acetal group at the end of the poly(ethylene
      glycol) (PEG) chain, that is, acetal-PEG-b-PAMA, was synthesized by a proprietary
      polymerization technique. Gold nanoparticles (GNPs) were prepared using the thus
      synthesized acetal-PEG-b-PAMA block copolymer. The PEG-b-PAMA not only acted as a
      reducing agent of aurate ions but also attached to the nanoparticle surface. The
      GNPs obtained had controlled sizes and narrow size distributions. They also
      showed high dispersion stability owing to the presence of PEG tethering chains on
      the surface. The same strategy should also be applicable to the fabrication of
      semiconductor quantum dots and inorganic porous nanoparticles. The preparation of
      nanoparticles in situ, i.e. in the presence of acetal-PEG-b-PAMA, gave the most
      densely packed polymer layer on the nanoparticle surface; this was not observed
      when coating preformed nanoparticles. PEG/polyamine block copolymer was more
      functional on the metal surface than PEG/polyamine graft copolymer, as confirmed
      by angle-dependent x-ray photoelectron spectroscopy. We successfully solubilized
      the C60 fullerene into aqueous media using acetal-PEG-b-PAMA. A C60/acetal-PEG-b
      PAMA complex with a size below 5 nm was obtained by dialysis. The preparation and
      characterization of these materials are described in this review.

PMID- 27877363
TI  - Plasmons in nanoscale and atomic-scale systems.
AB  - Plasmons in metallic nanomaterials exhibit very strong size and shape effects,
      and thus have recently gained considerable attention in nanotechnology,
      information technology, and life science. In this review, we overview the
      fundamental properties of plasmons in materials with various dimensionalities and
      discuss the optical functional properties of localized plasmon polaritons in
      nanometer-scale to atomic-scale objects. First, the pioneering works on plasmons
      by electron energy loss spectroscopy are briefly surveyed. Then, we discuss the
      effects of atomistic charge dynamics on the dispersion relation of propagating
      plasmon modes, such as those for planar crystal surface, atomic sheets and
      straight atomic wires. Finally, standing-wave plasmons, or antenna resonances of
      plasmon polariton, of some widely used nanometer-scale structures and atomic
      scale wires (the smallest possible plasmonic building blocks) are exemplified
      along with their applications.

PMID- 27877365
TI  - Metal-free phthalocyanine (H2Pc) molecule adsorbed on the Au(111) surface:
      formation of a wide domain along a single lattice direction.
AB  - Using low-temperature scanning tunneling microscopy (STM), we observed the
      bonding configuration of the metal-free phthalocyanine (H2Pc) molecule adsorbed
      on the Au(111) surface. A local lattice formation started from a quasi-square
      lattice aligned to the close-packed directions of the Au(111) surface. Although
      we expected the lattice alignment to be equally distributed along the three
      crystallographically equivalent directions, the domain aligned normal to the
      ridge of the herringbone structure was missing in the STM images. We attribute
      this effect to the uniaxial contraction of the reconstructed Au(111) surface that
      can account for the formation of a large lattice domain along a single
      crystallographical direction.

PMID- 27877364
TI  - Fabrication of quantum-dot devices in graphene.
AB  - We describe our recent experimental results on the fabrication of quantum-dot
      devices in a graphene-based two-dimensional system. Graphene samples were
      prepared by micromechanical cleavage of graphite crystals on a SiO2/Si substrate.
      We performed micro-Raman spectroscopy measurements to determine the number of
      layers of graphene flakes during the device fabrication process. By applying a
      nanofabrication process to the identified graphene flakes, we prepared a double
      quantum-dot device structure comprising two lateral quantum dots coupled in
      series. Measurements of low-temperature electrical transport show the device to
      be a series-coupled double-dot system with varied interdot tunnel coupling, the
      strength of which changes continuously and non-monotonically as a function of
      gate voltage.

PMID- 27877366
TI  - Preparation of fine, uniform nitrogen- and sulfur-modified TiO2 nanoparticles
      from titania nanotubes.
AB  - TiO2 nanoparticles modified with nitrogen and sulfur were prepared from titania
      nanotubes by a facile wet chemistry method. The samples synthesized with
      different thiourea/TiO2 ratios showed a uniform nanoparticle size distribution
      centred at approximately 10 nm with a developed specific surface area of 246 m2 g
      1. These modified nanosized photocatalysts exhibited higher photocatalytic
      activity for the degradation of gaseous isopropanol than unmodified titania
      nanotubes under visible illumination. This could be attributed to the synergistic
      effects of a large specific surface area, strong absorption in the visible
      region, a redshift in the adsorption edge, and surface adsorption modification
      induced by nitrogen and sulfur compounds.

PMID- 27877367
TI  - Photocatalytic paper using zinc oxide nanorods.
AB  - Zinc oxide (ZnO) nanorods were grown on a paper support prepared from soft wood
      pulp. The photocatalytic activity of a sheet of paper with ZnO nanorods embedded
      in its porous matrix has been studied. ZnO nanorods were firmly attached to
      cellulose fibers and the photocatalytic paper samples were reused several times
      with nominal decrease in efficiency. Photodegradation of up to 93% was observed
      for methylene blue in the presence of paper filled with ZnO nanorods upon
      irradiation with visible light at 963 Wm-2 for 120 min. Under similar conditions,
      photodegradation of approximately 35% was observed for methyl orange.
      Antibacterial tests revealed that the photocatalytic paper inhibits the growth of
      Escherichia coli under room lighting conditions.

PMID- 27877368
TI  - Potential use of only Yb2O3 in producing dense Si3N4 ceramics with high thermal
      conductivity by gas pressure sintering.
AB  - Yb2O3 is an efficient sintering additive for enhancing not only thermal
      conductivity but also the high-temperature mechanical properties of Si3N4
      ceramics. Here we report the fabrication of dense Si3N4 ceramics with high
      thermal conductivity by the gas pressure sintering of alpha-Si3N4 powder
      compacts, using only Yb2O3 as an additive, at 1900  degrees C under a nitrogen
      pressure of 1 MPa. The effects of Yb2O3 content, sample packing condition and
      sintering time on the densification, microstructure and thermal conductivity were
      investigated. Curves of the density plotted against the Yb2O3 content exhibited a
      characteristic 'N' shape with a local minimum at 3 mol% Yb2O3 and nearly complete
      densification below and above this concentration. The effects of the sample
      packing condition on the densification, microstructure and thermal conductivity
      strongly depended on the Yb2O3 content. The embedded condition led to more
      complete densification but also to a decrease in thermal conductivity from 119 to
      94 W m-1 K-1 upon 1 mol% Yb2O3 addition. The sample packing condition had little
      effect on the density and thermal conductivity (102-106 W m-1 K-1) at 7 mol%
      Yb2O3. The thermal conductivity value was strongly related to the microstructure.

PMID- 27877369
TI  - Voltage- and current-activated metal-insulator transition in VO2-based electrical
      switches: a lifetime operation analysis.
AB  - Vanadium dioxide is an intensively studied material that undergoes a temperature
      induced metal-insulator phase transition accompanied by a large change in
      electrical resistivity. Electrical switches based on this material show promising
      properties in terms of speed and broadband operation. The exploration of the
      failure behavior and reliability of such devices is very important in view of
      their integration in practical electronic circuits. We performed systematic
      lifetime investigations of two-terminal switches based on the electrical
      activation of the metal-insulator transition in VO2 thin films. The devices were
      integrated in coplanar microwave waveguides (CPWs) in series configuration. We
      detected the evolution of a 10 GHz microwave signal transmitted through the CPW,
      modulated by the activation of the VO2 switches in both voltage- and current
      controlled modes. We demonstrated enhanced lifetime operation of current
      controlled VO2-based switching (more than 260 million cycles without failure)
      compared with the voltage-activated mode (breakdown at around 16 million
      activation cycles). The evolution of the electrical self-oscillations of a VO2
      based switch induced in the current-operated mode is a subtle indicator of the
      material properties modification and can be used to monitor its behavior under
      various external stresses in sensor applications.

PMID- 27877370
TI  - Electrical quadruple hysteresis in Pd-doped vanadium pentoxide nanowires due to
      water adsorption.
AB  - Humidity-dependent current-voltage (I-V) characteristics of Pd-doped vanadium
      pentoxide nanowires (Pd-VONs) were investigated. Electrical quadruple hysteresis
      (QH) was observed and attributed to the large amount of water molecules adsorbed
      on the nanowires. Using QH in Pd-VONs, the reaction of water with PdO was
      interpreted as the water molecules are desorbed and then dissociated with
      increasing bias voltage. Owing to the dissociated H+ and OH- ions, PdO is reduced
      and oxidized. As a result, water molecules recombine as the bias voltage is
      decreased.

PMID- 27877371
TI  - Structural studies of a mixed-valence state in the incommensurate composite
      crystal Sr1.261CoO3.
AB  - The incommensurate modulated crystal structure of the hexagonal cobalt oxide
      Sr1.261CoO3 has been studied using a four-dimensional (4D) superspace profile
      analysis of neutron powder diffraction data. Sr1.261CoO3 is a composite crystal
      that consists of the [CoO3] and [2Sr] subsystems. The [CoO3] subsystem forms 1D
      chains that run parallel to the c-axis and consist of face-sharing CoO6 polyhedra
      with octahedral (Oh) and trigonal prismatic (TP) coordinations. The structure
      analysis reveals that the [CoO3] chains contain 73.9% Oh and 26.1% TP sites, and
      that the TP sites have longer Co-O bonds than the Oh sites: dav. =2.039(4) A (TP)
      and 1.895(3) A (Oh). The averaged Co bond valences are Co3.56(3)+ in the Oh sites
      and Co2.45(3)+ in the TP sites, suggesting that a considerable amount of Co3+
      ions are mixed with Co4+ions in the Oh sites and with Co2+ ions in the TP sites.
      The observed magnetic susceptibility can be well explained assuming that the
      compound has the Co mixed-valence state with the spin configurations of S=0 low
      spin state for Co3+(depsilon6), S=1/2 low-spin state for Co4+(depsilon5) and
      S=3/2 high-spin state for Co2+(depsilon5dgamma2). The Weiss temperature,
      approximately 0.8 K, implies that Sr1.261CoO3 naturally assumes a Curie
      paramagnetic state, probably owing to the obstruction of the intrachain magnetic
      interaction by the nonmagnetic Co3+ ions. These results suggest that the
      nonmagnetic Co3+ ions play an essential role in the magnetism of Sr2gammaCoO3
      systems.

PMID- 27877372
TI  - Effects of surfactants on spinning carbon nanotube fibers by an electrophoretic
      method.
AB  - Thin fibers were spun from a colloidal solution of single-walled carbon nanotubes
      (SWNTs) using an electrophoretic method. Sodium dodecylbenzenesulfonate (NaDDBS)
      was chosen as a surfactant and showed good performance owing to its special
      chemical structure. The highest spinning velocity reached 0.5 mm s-1. The
      resulting SWNT fibers had a tensile strength of 400 MPa and a conductivity of 355
      S cm-1. Their mechanical and electrical properties were markedly improved after
      adding NaDDBS as the dispersant in water.

PMID- 27877373
TI  - Hybrid processing and anisotropic sintering shrinkage in textured ZnO ceramics.
AB  - We have studied the combined effects of the templated grain growth and magnetic
      alignment processes on sintering, anisotropic sintering shrinkage, microstructure
      development and texture in ZnO ceramics. Suspensions of 0-10 vol % ZnO template
      particles were slip cast in a 12 T rotating magnetic field. Sintering and texture
      characteristics were investigated via thermomechanical analysis and electron
      backscatter diffraction, respectively. Sintering as well as texture
      characteristics depend on template concentration. For the studied ZnO system,
      there is a critical template concentration (2 vol % in this study) above which
      densification is limited by the templates owing to constrained sintering. Below
      this limit, the densification is enhanced and the anisotropic shrinkage is
      reduced, which is attributed to densifying characteristics of the templates.

PMID- 27877374
TI  - 'Beautiful' unconventional synthesis and processing technologies of
      superconductors and some other materials.
AB  - Superconducting materials have contributed significantly to the development of
      modern materials science and engineering. Specific technological solutions for
      their synthesis and processing helped in understanding the principles and
      approaches to the design, fabrication and application of many other materials. In
      this review, we explore the bidirectional relationship between the general and
      particular synthesis concepts. The analysis is mostly based on our studies where
      some unconventional technologies were applied to different superconductors and
      some other materials. These technologies include spray-frozen freeze-drying, fast
      pyrolysis, field-assisted sintering (or spark plasma sintering), nanoblasting,
      processing in high magnetic fields, methods of control of supersaturation and
      migration during film growth, and mechanical treatments of composite wires. The
      analysis provides future research directions and some key elements to define the
      concept of 'beautiful' technology in materials science. It also reconfirms the
      key position and importance of superconductors in the development of new
      materials and unconventional synthesis approaches.

PMID- 27877375
TI  - Technological advances in electrospinning of nanofibers.
AB  - Progress in the electrospinning techniques has brought new methods for the
      production and construction of various nanofibrous assemblies. The parameters
      affecting electrospinning include electrical charges on the emerging jet, charge
      density and removal, as well as effects of external perturbations. The solvent
      and the method of fiber collection also affect the construction of the final
      nanofibrous architecture. Various techniques of yarn spinning using solid and
      liquid surfaces as well as surface-free collection are described and compared in
      this review. Recent advances allow production of 3D nanofibrous scaffolds with a
      desired microstructure. In the area of tissue regeneration and bioengineering, 3D
      scaffolds should bring nanofibrous technology closer to clinical applications.
      There is sufficient understanding of the electrospinning process and experimental
      results to suggest that precision electrospinning is a real possibility.

PMID- 27877376
TI  - Atomic switches: atomic-movement-controlled nanodevices for new types of
      computing.
AB  - Atomic switches are nanoionic devices that control the diffusion of metal cations
      and their reduction/oxidation processes in the switching operation to
      form/annihilate a metal atomic bridge, which is a conductive path between two
      electrodes in the on-state. In contrast to conventional semiconductor devices,
      atomic switches can provide a highly conductive channel even if their size is of
      nanometer order. In addition to their small size and low on-resistance, their
      nonvolatility has enabled the development of new types of programmable devices,
      which may achieve all the required functions on a single chip. Three-terminal
      atomic switches have also been developed, in which the formation and annihilation
      of a metal atomic bridge between a source electrode and a drain electrode are
      controlled by a third (gate) electrode. Three-terminal atomic switches are
      expected to enhance the development of new types of logic circuits, such as
      nonvolatile logic. The recent development of atomic switches that use a metal
      oxide as the ionic conductive material has enabled the integration of atomic
      switches with complementary metal-oxide-semiconductor (CMOS) devices, which will
      facilitate the commercialization of atomic switches. The novel characteristics of
      atomic switches, such as their learning and photosensing abilities, are also
      introduced in the latter part of this review.

PMID- 27877377
TI  - Zinc stannate nanostructures: hydrothermal synthesis.
AB  - Nanostructured binary semiconducting metal oxides have received much attention in
      the last decade owing to their unique properties rendering them suitable for a
      wide range of applications. In the quest to further improve the physical and
      chemical properties, an interest in ternary complex oxides has become noticeable
      in recent times. Zinc stannate or zinc tin oxide (ZTO) is a class of ternary
      oxides that are known for their stable properties under extreme conditions,
      higher electron mobility compared to its binary counterparts and other
      interesting optical properties. The material is thus ideal for applications from
      solar cells and sensors to photocatalysts. Among the different methods of
      synthesizing ZTO nanostructures, the hydrothermal method is an attractive green
      process that is carried out at low temperatures. In this review, we summarize the
      conditions leading to the growth of different ZTO nanostructures using the
      hydrothermal method and delve into a few of its applications reported in the
      literature.

PMID- 27877378
TI  - Tailoring the morphology and crystallinity of poly(L-lactide acid) electrospun
      membranes.
AB  - Biodegradable poly(L-lactic acid) (PLLA) microfibers were prepared by
      electrospinning by varying the applied potential, solution flow rate and
      collector conditions. PLLA fibers with smoothly oriented and random morphologies
      were obtained and characterized by scanning electron microscopy. The optimum
      fiber orientation was obtained at 1000 rpm using a 20.3 cm diameter collecting
      drum, while for higher and lower drum rotation speeds, the rapid random motion of
      the jets resulted in a random fiber distribution. The deformation of the jet with
      rapid solidification during electrospinning often results in a metastable phase.
      PLLA electrospun fibers are amorphous but contain numerous crystal nuclei that
      rapidly grow when the sample is heated to 70-140  degrees C. In this way, the
      degree of crystallinity of the fibers can be tailored between 0 and 50% by
      annealing. Infrared transmission spectra revealed that the processing conditions
      do not affect the PLLA samples at the molecular level and that the crystallinity
      of the samples is related to the presence of alpha-crystals.

PMID- 27877379
TI  - Effect of electrical and mechanical poling history on domain orientation and
      piezoelectric properties of soft and hard PZT ceramics.
AB  - The superior piezoelectric properties of all polycrystalline ferroelectrics are
      based on the extent of non-180 degrees  domain wall motion under electrical and
      mechanical poling loads. To distinguish between 180 degrees  and non-180 degrees 
      domain wall motion in a soft-doped and a hard-doped lead zirconate titanate (PZT)
      ceramic, domain texture measurements were performed using x-ray and neutron
      diffraction after different loading procedures. Comparing the results to
      measurements of the remanent strain and piezoelectric coefficient allowed the
      differentiation between different microstructural contributions to the
      macroscopic parameters. Both types of ceramic showed similar behavior under
      electric field, but the hard-doped material was more susceptible to mechanical
      load. A considerable fraction of the piezoelectric coefficient originated from
      poling by the preferred orientation of 180 degrees  domains.

PMID- 27877380
TI  - A novel shortened electrospun nanofiber modified with a 'concentrated' polymer
      brush.
AB  - We report the fabrication of shortened electrospun polymer fibers with a well
      defined concentrated polymer brush. We first prepared electrospun nanofibers from
      a random copolymer of styrene and 4-vinylbenzyl 2-bromopropionate, with number
      average molecular weight Mn=105 200 and weight-average molecular weight Mw=296
      700 (Mw/Mn=2.82). The fibers had a diameter of 593+/-74 nm and contained
      initiating sites for surface-initiated atom transfer radical polymerization (SI
      ATRP). Then, SI-ATRP of hydrophilic styrene sodium sulfonate (SSNa) was carried
      out in the presence of a free initiator and the hydrophobic fibers. Gel
      permeation chromatography confirmed that Mn and Mw/Mn values were almost the same
      for free polymers and graft polymers. Mn agreed well with the theoretical
      prediction, and Mw/Mn was relatively low (<1.3) in all the examined cases,
      indicating that this polymerization proceeded in a living manner. Using the
      values of the graft amount measured by Fourier transform infrared spectroscopy,
      the surface area, and Mn, we calculated the graft density sigma as 0.22 chains nm
      2. This value was nearly equal to the density obtained on silicon wafers
      (sigma=0.24 chains nm-2), which is categorized into the concentrated brush
      regime. Finally, we mechanically cut the fibers with a concentrated poly(SSNa)
      brush by a homogenizer. With increasing cutting time, the fiber length became
      shorter and more homogenous (11+/-17 MUm after 3 h). The shortened fibers
      exhibited excellent water dispersibility owing to the hydrophilic poly(SSNa)
      brush layer.

PMID- 27877381
TI  - Kinetics of martensitic transformations in magnetic field or under hydrostatic
      pressure.
AB  - We have recently constructed a phenomenological theory that provides a unified
      explanation for athermal and isothermal martensitic transformation processes. On
      the basis of this theory, we predict some properties of martensitic
      transformation and confirm them experimentally using some Fe-based alloys and a
      Ni-Co-Mn-In magnetic shape memory alloy.

PMID- 27877382
TI  - Soft particle analysis of electrokinetics of biological cells and their model
      systems.
AB  - In this article, we review the applications of a novel theory (Ohshima 2009 Sci.
      Technol. Adv. Mater.10 063001) to the analysis of electrokinetic data for various
      soft particles, that is, particles covered with an ion-permeable surface layer of
      polyelectrolytes. Soft particles discussed in this review include various
      biological cells and hydrogel-coated particles as a model of biological cells.
      Cellular transformations increase the concentration of sialic acid of
      glycoproteins and are associated with blocked biosynthesis of glycolipids and
      aberrant expression of the developmentally programmed biosynthetic pathway. The
      change in shape or biological function of cells may affect their surface
      properties and can be detected by electrokinetic measurements. The experimental
      results were analyzed with Ohshima's electrokinetic formula for soft particles
      and soft surfaces. As a model system, hydrogel surfaces that mimic biological
      surfaces were also prepared and their surface properties were studied.

PMID- 27877383
TI  - High-mobility solution-processed copper phthalocyanine-based organic field-effect
      transistors.
AB  - Solution-processed films of 1,4,8,11,15,18,22,25-octakis(hexyl) copper
      phthalocyanine (CuPc6) were utilized as an active semiconducting layer in the
      fabrication of organic field-effect transistors (OFETs) in the bottom-gate
      configurations using chemical vapour deposited silicon dioxide (SiO2) as gate
      dielectrics. The surface treatment of the gate dielectric with a self-assembled
      monolayer of octadecyltrichlorosilane (OTS) resulted in values of 4*10-2 cm2 V-1
      s-1 and 106 for saturation mobility and on/off current ratio, respectively. This
      improvement was accompanied by a shift in the threshold voltage from 3 V for
      untreated devices to -2 V for OTS treated devices. The trap density at the
      interface between the gate dielectric and semiconductor decreased by about one
      order of magnitude after the surface treatment. The transistors with the OTS
      treated gate dielectrics were more stable over a 30-day period in air than
      untreated ones.

PMID- 27877384
TI  - Tuning optical properties of poly(3-hexylthiophene) nanoparticles through
      hydrothermal processing.
AB  - Poly(3-hexylthiophene) (P3HT) nanoparticles (NPs) were prepared by a
      reprecipitation method. Hydrothermal processing applied external pressure to the
      pristine P3HT NPs at temperatures ranging from 60 to 150  degrees C. Optical
      absorption and photoluminescence (PL) spectra for the hydrothermally treated P3HT
      NPs varied markedly with the processing temperature. With increasing treatment
      temperature, the absorption peak broadened and the peak position shifted from 510
      to 623 nm; moreover, the intensity ratio of the 0-1 to 0-0 emission varied. These
      changes were caused by interactions between the P3HT main chains and alkyl side
      groups and conformational modifications induced by the high pressure during the
      hydrothermal process. The evolution of the optical absorption spectra of the P3HT
      NPs during the hydrothermal processing was strongly correlated with the variation
      of PL excitation spectra and with the PL emission spectra of a single NP.

PMID- 27877386
TI  - Characterization of magnetic domain walls using electron magnetic chiral
      dichroism.
AB  - Domain walls and spin states of permalloy were investigated by electron magnetic
      chiral dichroism (EMCD) technique in Lorentz imaging mode using a JEM-2100F
      transmission electron microscope. EMCD signals from both Fe and Ni L3,2 edges
      were detected from the Bloch lines but not from the adjacent main wall. The
      magnetic polarity orientation of the circular Bloch line is opposite to that of
      the cross Bloch line. The orientations of Fe and Ni spins are parallel rather
      than antiparallel, both at the cross Bloch line and circular Bloch line.

PMID- 27877385
TI  - Experimental study of the Ca-Mg-Zn system using diffusion couples and key alloys.
AB  - Nine diffusion couples and 32 key samples were prepared to map the phase diagram
      of the Ca-Mg-Zn system. Phase relations and solubility limits were determined for
      binary and ternary compounds using scanning electron microscopy, electron probe
      microanalysis and x-ray diffraction (XRD). The crystal structure of the ternary
      compounds was studied by XRD and electron backscatter diffraction. Four ternary
      intermetallic (IM) compounds were identified in this system: Ca3Mg x Zn15-x (4.6
      ? x ? 12 at 335  degrees C, IM1), Ca14.5Mg15.8Zn69.7 (IM2), Ca2Mg5Zn13 (IM3) and
      Ca1.5Mg55.3Zn43.2 (IM4). Three binary compounds were found to have extended solid
      solubility into ternary systems: CaZn11, CaZn13 and Mg2Ca form substitutional
      solid solutions where Mg substitutes for Zn atoms in the first two compounds, and
      Zn substitutes for both Ca and Mg atoms in Mg2Ca. The isothermal section of the
      Ca-Mg-Zn phase diagram at 335  degrees C was constructed on the basis of the
      obtained experimental results. The morphologies of the diffusion couples in the
      Ca-Mg-Zn phase diagram at 335  degrees C were studied. Depending on the terminal
      compositions of the diffusion couples, the two-phase regions in the diffusion
      zone have either a tooth-like morphology or contain a matrix phase with isolated
      and/or dendritic precipitates.

PMID- 27877388
TI  - Focus on Advanced Ceramics.

PMID- 27877387
TI  - Mesoporous tin-doped indium oxide thin films: effect of mesostructure on
      electrical conductivity.
AB  - We present a versatile method for the preparation of mesoporous tin-doped indium
      oxide (ITO) thin films via dip-coating. Two poly(isobutylene)-b
      poly(ethyleneoxide) (PIB-PEO) copolymers of significantly different molecular
      weight (denoted as PIB-PEO 3000 and PIB-PEO 20000) are used as templates and are
      compared with non-templated films to clarify the effect of the template size on
      the crystallization and, thus, on the electrochemical properties of mesoporous
      ITO films. Transparent, mesoporous, conductive coatings are obtained after
      annealing at 500  degrees C; these coatings have a specific resistance of 0.5
      Omega cm at a thickness of about 100 nm. Electrical conductivity is improved by
      one order of magnitude by annealing under a reducing atmosphere. The two types of
      PIB-PEO block copolymers create mesopores with in-plane diameters of 20-25 and 35
      45 nm, the latter also possessing correspondingly thicker pore walls. Impedance
      measurements reveal that the conductivity is significantly higher for films
      prepared with the template generating larger mesopores. Because of the same size
      of the primary nanoparticles, the enhanced conductivity is attributed to a higher
      conduction path cross section. Prussian blue was deposited electrochemically
      within the films, thus confirming the accessibility of their pores and their
      functionality as electrode material.

PMID- 27877389
TI  - Magnesium dititanate (MgTi2O5) with pseudobrookite structure: a review.
AB  - Magnesium dititanate (MgTi2O5, MT2) has been synthesized since the early 1930s.
      It has the pseudobrookite structure (general formula Me3O5), corresponding to the
      Mg-enriched artificial endmember of the Fe2TiO5 (pseudobrookite)-FeTi2O5
      (ferropseudobrookite)-Mg0.5Fe0.5Ti2O5 (armalcolite) solid solution. Since MgTi2O5
      has relativity high thermal stability among pseudobrookite-type phases, it is
      expected to be a well-balanced low-thermal-expansion material. Here we review
      both the historical and recent studies on MgTi2O5, particularly on its crystal
      structure, cation order-disorder, physical properties and synthesis methods.

PMID- 27877390
TI  - Point defects in ZnO: an approach from first principles.
AB  - Recent first-principles studies of point defects in ZnO are reviewed with a focus
      on native defects. Key properties of defects, such as formation energies, donor
      and acceptor levels, optical transition energies, migration energies and atomic
      and electronic structure, have been evaluated using various approaches including
      the local density approximation (LDA) and generalized gradient approximation
      (GGA) to DFT, LDA+U/GGA+U, hybrid Hartree-Fock density functionals, sX and GW
      approximation. Results significantly depend on the approximation to exchange
      correlation, the simulation models for defects and the post-processes to correct
      shortcomings of the approximation and models. The choice of a proper approach is,
      therefore, crucial for reliable theoretical predictions. First-principles studies
      have provided an insight into the energetics and atomic and electronic structures
      of native point defects and impurities and defect-induced properties of ZnO.
      Native defects that are relevant to the n-type conductivity and the non
      stoichiometry toward the O-deficient side in reduced ZnO have been debated. It is
      suggested that the O vacancy is responsible for the non-stoichiometry because of
      its low formation energy under O-poor chemical potential conditions. However, the
      O vacancy is a very deep donor and cannot be a major source of carrier electrons.
      The Zn interstitial and anti-site are shallow donors, but these defects are
      unlikely to form at a high concentration in n-type ZnO under thermal equilibrium.
      Therefore, the n-type conductivity is attributed to other sources such as
      residual impurities including H impurities with several atomic configurations, a
      metastable shallow donor state of the O vacancy, and defect complexes involving
      the Zn interstitial. Among the native acceptor-type defects, the Zn vacancy is
      dominant. It is a deep acceptor and cannot produce a high concentration of holes.
      The O interstitial and anti-site are high in formation energy and/or are
      electrically inactive and, hence, are unlikely to play essential roles in
      electrical properties. Overall defect energetics suggests a preference for the
      native donor-type defects over acceptor-type defects in ZnO. The O vacancy, Zn
      interstitial and Zn anti-site have very low formation energies when the Fermi
      level is low. Therefore, these defects are expected to be sources of a strong
      hole compensation in p-type ZnO. For the n-type doping, the compensation of
      carrier electrons by the native acceptor-type defects can be mostly suppressed
      when O-poor chemical potential conditions, i.e. low O partial pressure
      conditions, are chosen during crystal growth and/or doping.

PMID- 27877391
TI  - New functionalities in abundant element oxides: ubiquitous element strategy.
AB  - While most ceramics are composed of ubiquitous elements (the ten most abundant
      elements within the Earth's crust), many advanced materials are based on rare
      elements. A 'rare-element crisis' is approaching owing to the imbalance between
      the limited supply of rare elements and the increasing demand. Therefore, we
      propose a 'ubiquitous element strategy' for materials research, which aims to
      apply abundant elements in a variety of innovative applications. Creation of
      innovative oxide materials and devices based on conventional ceramics is one
      specific challenge. This review describes the concept of ubiquitous element
      strategy and gives some highlights of our recent research on the synthesis of
      electronic, thermionic and structural materials using ubiquitous elements.

PMID- 27877392
TI  - Hydrogen production using zinc-doped carbon nitride catalyst irradiated with
      visible light.
AB  - Recently, graphitic carbon nitride (g-C3N4) has been investigated as a
      photocatalyst for water splitting and organic dye degradation. In this study, we
      have developed a simple soft-chemical method of doping Zn into g-C3N4 to prepare
      a metal-containing carbon nitride. The doping was confirmed by x-ray
      photoelectron spectroscopy, and diffusion reflectance spectra revealed a
      significant red shift in the absorption edge of Zn/g-C3N4. This hybrid material
      shows high photocatalytic activity and good stability for hydrogen evolution from
      an aqueous methanol solution under visible light irradiation (lambda>=420 nm).
      The hydrogen evolution rate was more than 10 times higher for a 10%-Zn/g-C3N4
      sample (59.5 MUmol h-1) than for pure g-C3N4. The maximum quantum yield was 3.2%
      at 420 nm.

PMID- 27877393
TI  - Mechanochemically synthesized CsH2PO4-H3PW12O40 composites as proton-conducting
      electrolytes for fuel cell systems in a dry atmosphere.
AB  - Cesium dihydrogen phosphate (CsH2PO4, CDP) and dodecaphosphotungstic acid
      (H3PW12O40.nH2O, WPA.nH2O) were mechanochemically milled to synthesize CDP-WPA
      composites. The ionic conductivities of these composites were measured by an ac
      impedance method under anhydrous conditions. Despite the synthesis temperatures
      being much lower than the dehydration and phase-transition temperatures of CDP
      under anhydrous conditions, the ionic conductivities of the studied composites
      increased significantly. The highest ionic conductivity of 6.58*10-4 Scm-1 was
      achieved for the 95CDP.5WPA composite electrolyte at 170  degrees C under
      anhydrous conditions. The ionic conduction was probably induced in the percolated
      interfacial phase between CDP and WPA. The phenomenon of high ionic conduction
      differs for the CDP-WPA composite and pure CDP or pure WPA under anhydrous
      conditions. The newly developed hydrogen interaction between CDP and WPA supports
      anhydrous proton conduction in the composites.

PMID- 27877394
TI  - Diffraction contrast analysis of 90 degrees  and 180 degrees  ferroelectric
      domain structures of PbTiO3 thin films.
AB  - The ferroelectric domain structure of a PbTiO3 thin film on (100) SrTiO3 has been
      investigated by transmission electron microscopy (TEM). Two types of a-domain
      were found: one extended through the film to the surface and another comprised
      small a-domains confined within the film. Dark-field TEM (DFTEM) observation
      revealed that 180 degrees  domains formed near the substrate and stopped their
      growth 100 nm away from the substrate. The DFTEM observation also revealed that
      90 degrees  domain boundaries had head-to-tail structures. To confirm the
      polarization direction obtained by experiments, diffracted intensities under a
      two-beam condition were simulated using the extended Darwin-Howie-Whelan
      equations. On the basis of the obtained results, a ferroelectric domain structure
      model of PbTiO3 thin films on SrTiO3 is proposed.

PMID- 27877395
TI  - Photoluminescence properties of beta-SiAlON:Yb2+, a novel green-emitting phosphor
      for white light-emitting diodes.
AB  - We have synthesized Yb2+-activated Si6-z Al z O z N8-z (0.05?z?2.3, 0.03 mol%
      ?Yb2+?0.7 mol%) green phosphors by solid-state reaction at 1900  degrees C for 2
      h under a nitrogen pressure of 1.0 MPa. Phase purity, photoluminescence and its
      thermal quenching were investigated. A single phase was obtained for all values
      of z and Yb2+ concentration. A distinct emission band was observed at 540 nm
      originating from the 5d-4f electronic transition in Yb2+ under 480 nm excitation.
      The photoluminescence properties mainly depended on the Yb2+ concentration and
      chemical composition of the matrix. The resultant phosphor showed high thermal
      stability, that is, the emission intensity at 150  degrees C was about 82% of
      that measured at room temperature. The experimental results indicate that beta
      SiAlON:Yb2+ is a potential green phosphor for white light-emitting diodes (LEDs),
      which use blue LEDs as the primary light source.

PMID- 27877396
TI  - Bone formation in vivo induced by Cbfa1-carrying adenoviral vectors released from
      a biodegradable porous beta-tricalcium phosphate (beta-TCP) material.
AB  - Overexpression of Cbfa1 (a transcription factor indispensable for osteoblastic
      differentiation) is expected to induce the formation of bone directly and
      indirectly in vivo by accelerating osteoblastic differentiation. Adenoviral
      vectors carrying the cDNA of Cbfa1/til-1(Adv-Cbf1) were allowed to be adsorbed
      onto porous blocks of beta-tricalcium phosphate (beta-TCP), a biodegradable
      ceramic, which were then implanted subcutaneously and orthotopically into bone
      defects. The adenoviral vectors were released sustainingly by biodegradation,
      providing long-term expression of the genes. Results of the subcutaneous
      implantation of Adv-Cbfa1-adsorbed beta-TCP/osteoprogenitor cells suggest that a
      larger amount of bone formed in the pores of the implant than in the control
      material. Regarding orthotopic implantation into bone defects, the released Adv
      Cbfa1 accelerated regeneration in the cortical bone, whereas it induced bone
      resorption in the marrow cavity. A safer gene transfer using a smaller amount of
      the vector was achieved using biodegradable porous beta-TCP as a carrier.

PMID- 27877398
TI  - Fabrication of silica glass containing yellow oxynitride phosphor by the sol-gel
      process.
AB  - We have prepared silica glass by the sol-gel method and studied its ability to
      disperse the Ca-alpha-SiAlON:Eu2+ phosphor for application in white light
      emitting diodes (LEDs). The emission color generated by irradiating doped glass
      with a blue LED at 450 nm depended on the concentration of SiAlON and the glass
      thickness, resulting in nearly white light. The luminescence efficiency of 1-mm
      thick glass depended on the SiAlON concentration, and was highest at 4 wt%
      SiAlON.

PMID- 27877397
TI  - Fabrication of two-dimensional close-packed shell structure in ceramic thin
      films.
AB  - TiO2 thin films with a periodical two-dimensional close-packed hemispherical
      structure were prepared on Si substrates using pulsed laser deposition and close
      packed monolayer polystyrene colloidal crystals as a template. Compared with
      conventional methods, which use a top-down approach, this route supports low-cost
      production of a periodic structure. Additionally, it is applicable to various
      ceramics for use in applications related to photonic crystals, surface self
      cleaning materials, data storage media, bioassays, and so on.

PMID- 27877399
TI  - Magnetic and optical properties of MgAl2O4-(Ni0.5Zn0.5)Fe2O4 thin films prepared
      by pulsed laser deposition.
AB  - Thin films composed of MgAl2O4 and (Ni0.5Zn0.5)Fe2O4 ([MA(100-x)-NZFx] films)
      were grown on fused SiO2 substrates by pulsed laser deposition. X-ray diffraction
      measurements revealed that the films were polycrystalline, and that their lattice
      constant varied linearly with composition, indicating the formation of a solid
      solution. The film with x=60 was paramagnetic and those with x >= 70 were
      ferromagnetic. The films had a transparency above 75% in the visible range, but
      the transparency decreased with the x value. The optical band gaps were 2.95,
      2.55, 2.30 and 1.89 eV for x=20, 40, 60, 80 and 100, respectively. The Faraday
      rotation angle increased with x in the visible range, and the film with x=70
      exhibited a value of 2000 degrees cm-1 at 570 nm, which is comparable to the
      rotation angle of Y3Fe5O12. Owing to their high transparency, which extends into
      the visible range, the [MA(100-x)-NZFx] films can be used in novel magneto
      optical devices.

PMID- 27877400
TI  - Ultrafast zone-center coherent lattice dynamics in ferroelectric lithium
      tantalate.
AB  - Femtosecond time-resolved pump-probe experiments were carried out to study
      ultrafast lattice dynamics of ferroelectric lithium tantalate. Both the fully
      symmetric (A1 mode) and doubly degenerate (E mode) coherent phonons at the center
      of the Brillouin zone were excited via impulsive stimulated Raman scattering, as
      confirmed by the excitation intensity dependence.

PMID- 27877401
TI  - Secondary electron emission and glow discharge properties of 12CaO.7Al2O3
      electride for fluorescent lamp applications.
AB  - 12CaO.7Al2O3 electride, a sub-nanoporous compound having a work function of 2.4
      eV, was examined as a candidate cathode material in fluorescent lamps. The
      electron emission yield was higher and the discharge voltage was lower for
      12CaO.7Al2O3 than for existing cathode materials such as Ni, Mo or W; therefore,
      the energy consumption of the fluorescent lamps can be improved using
      12CaO.7Al2O3 cathodes. Prototype glow-discharge lamps using 12CaO.7Al2O3 were
      constructed and exhibited reasonable durability.

PMID- 27877402
TI  - Competitive adsorption of fibronectin and albumin on hydroxyapatite nanocrystals.
AB  - Competitive adsorption of two-component solutions containing fibronectin (Fn) and
      albumin (Ab) on hydroxyapatite (HAp) nanocrystals was analyzed in situ using the
      quartz crystal microbalance with dissipation (QCM-D) technique. Adsorption of the
      one-component protein (Fn or Ab) and the two-component proteins adjusted to
      different molar ratios of Fn to Ab at a fixed Fn concentration was investigated.
      The frequency shift (Deltaf; Hz) and the dissipation energy shift (DeltaD) were
      measured with the QCM-D technique, and the viscoelastic changes of adlayers were
      evaluated by the saturated DeltaD/Deltaf value and the Voigt-based viscoelastic
      model. For the adsorption of the one-component protein, the Fn adlayer showed a
      larger mass and higher viscoelasticity than the Ab adlayer, indicating the higher
      affinity of Fn on HAp. For the adsorption of the two-component proteins, the
      viscoelastic properties of the adlayers became elastic with increase in Ab
      concentration, whereas the adsorption mass was similar to that of Fn in the one
      component solution regardless of the Ab concentration. The specific binding mass
      of the Ab antibody to the adlayers increased with increase in Ab concentration,
      whereas that of the Fn antibody decreased. Therefore, Fn preferentially adsorbs
      on HAp and Ab subsequently interacts with the adlayers, indicating that the
      interfacial viscoelasticity of the adlayers was dominated by the interaction
      between Fn and Ab.

PMID- 27877403
TI  - Alkoxide-based precursors for direct drawing of metal oxide micro- and
      nanofibres.
AB  - The invention of electrospinning has solved the problem of producing micro- and
      nanoscaled metal oxide fibres in bulk quantities. However, until now no methods
      have been available for preparing a single nanofibre of a metal oxide. In this
      work, the direct drawing method was successfully applied to produce metal oxide
      (SnO2, TiO2, ZrO2, HfO2 and CeO2) fibres with a high aspect ratio (up to 10 000)
      and a diameter as small as 200 nm. The sol-gel processing includes consumption of
      precursors obtained from alkoxides by aqueous or non-aqueous polymerization.
      Shear thinning of the precursors enables pulling a material into a fibre. This
      rheological behaviour can be explained by sliding of particles owing to external
      forces. Transmission (propagation) of light along microscaled fibres and their
      excellent surface morphology suggest that metal oxide nanofibres can be directly
      drawn from sol precursors for use in integrated photonic systems.

PMID- 27877404
TI  - Configuration and local elastic interaction of ferroelectric domains and misfit
      dislocation in PbTiO3/SrTiO3 epitaxial thin films.
AB  - We have studied the strain field around the 90 degrees  domains and misfit
      dislocations in PbTiO3/SrTiO3 (001) epitaxial thin films, at the nanoscale, using
      the geometric phase analysis (GPA) combined with high-resolution transmission
      electron microscopy (HRTEM) and high-angle annular dark field--scanning
      transmission electron microscopy (HAADF-STEM). The films typically contain a
      combination of a/c-mixed domains and misfit dislocations. The PbTiO3 layer was
      composed from the two types of the a-domain (90 degrees  domain): a typical a/c
      mixed domain configuration where a-domains are 20-30 nm wide and nano sized
      domains with a width of about 3 nm. In the latter case, the nano sized a-domain
      does not contact the film/substrate interface; it remains far from the interface
      and stems from the misfit dislocation. Strain maps obtained from the GPA of HRTEM
      images show the elastic interaction between the a-domain and the dislocations.
      The normal strain field and lattice rotation match each other between them.
      Strain maps reveal that the a-domain nucleation takes place at the misfit
      dislocation. The lattice rotation around the misfit dislocation triggers the
      nucleation of the a-domain; the normal strains around the misfit dislocation
      relax the residual strain in a-domain; then, the a-domain growth takes place,
      accompanying the introduction of the additional dislocation perpendicular to the
      misfit dislocation and the dissociation of the dislocations into two pairs of
      partial dislocations with an APB, which is the bottom boundary of the a-domain.
      The novel mechanism of the nucleation and growth of 90 degrees  domain in
      PbTiO3/SrTiO3 epitaxial system has been proposed based on above the results.

PMID- 27877405
TI  - Bimodal activated carbons derived from resorcinol-formaldehyde cryogels.
AB  - Resorcinol-formaldehyde cryogels prepared at different dilution ratios have been
      activated with phosphoric acid at 450  degrees C and compared with their
      carbonaceous counterparts obtained by pyrolysis at 900  degrees C. Whereas the
      latter were, as expected, highly mesoporous carbons, the former cryogels had very
      different pore textures. Highly diluted cryogels allowed preparation of
      microporous materials with high surface areas, but activation of initially dense
      cryogels led to almost non-porous carbons, with much lower surface areas than
      those obtained by pyrolysis. The optimal acid concentration for activation,
      corresponding to stoichiometry between molecules of acid and hydroxyl groups, was
      2 M l-1, and the acid-cryogel contact time also had an optimal value. Such
      optimization allowed us to achieve surface areas and micropore volumes among the
      highest ever obtained by activation with H3PO4, close to 2200 m2 g-1 and 0.7 cm3
      g-1, respectively. Activation of diluted cryogels with a lower acid concentration
      of 1.2 M l-1 led to authentic bimodal activated carbons, having a surface area as
      high as 1780 m2 g-1 and 0.6 cm3 g-1 of microporous volume easily accessible
      through a widely developed macroporosity.

PMID- 27877406
TI  - Novel approach to the fabrication of an artificial small bone using a combination
      of sponge replica and electrospinning methods.
AB  - In this study, a novel artificial small bone consisting of ZrO2-biphasic calcium
      phosphate/polymethylmethacrylate-polycaprolactone-hydroxyapatite (ZrO2-BCP/PMMA
      PCL-HAp) was fabricated using a combination of sponge replica and electrospinning
      methods. To mimic the cancellous bone, the ZrO2/BCP scaffold was composed of
      three layers, ZrO2, ZrO2/BCP and BCP, fabricated by the sponge replica method.
      The PMMA-PCL fibers loaded with HAp powder were wrapped around the ZrO2/BCP
      scaffold using the electrospinning process. To imitate the Haversian canal region
      of the bone, HAp-loaded PMMA-PCL fibers were wrapped around a steel wire of 0.3
      mm diameter. As a result, the bundles of fiber wrapped around the wires imitated
      the osteon structure of the cortical bone. Finally, the ZrO2/BCP scaffold was
      surrounded by HAp-loaded PMMA-PCL composite bundles. After removal of the steel
      wires, the ZrO2/BCP scaffold and bundles of HAp-loaded PMMA-PCL formed an
      interconnected structure resembling the human bone. Its diameter, compressive
      strength and porosity were approximately 12 mm, 5 MPa and 70%, respectively, and
      the viability of MG-63 osteoblast-like cells was determined to be over 90% by the
      MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. This
      artificial bone shows excellent cytocompatibility and is a promising bone
      regeneration material.

PMID- 27877407
TI  - Thermodynamic criteria for the removal of impurities from end-of-life magnesium
      alloys by evaporation and flux treatment.
AB  - In this paper, the possibility of removing impurities during magnesium recycling
      with pyrometallurgical techniques has been evaluated by using a thermodynamic
      analysis. For 25 different elements that are likely to be contained in industrial
      magnesium alloys, the equilibrium distribution ratios between the metal, slag and
      gas phases in the magnesium remelting process were calculated assuming binary
      systems of magnesium and an impurity element. It was found that calcium,
      gadolinium, lithium, ytterbium and yttrium can be removed from the remelted end
      of-life (EoL) magnesium products by oxidization. Calcium, cerium, gadolinium,
      lanthanum, lithium, plutonium, sodium, strontium and yttrium can be removed by
      chlorination with a salt flux. However, the other elements contained in magnesium
      alloy scrap are scarcely removed and this may contribute toward future
      contamination problems. The third technological option for the recycling of EoL
      magnesium products is magnesium recovery by a distillation process. Based on
      thermodynamic considerations, it is predicted that high-purity magnesium can be
      recovered through distillation because of its high vapor pressure, yet there is a
      limit on recoverability that depends on the equilibrium vapor pressure of the
      alloying elements and the large energy consumption. Therefore, the sustainable
      recycling of EoL magnesium products should be an important consideration in the
      design of advanced magnesium alloys or the development of new refining processes.

PMID- 27877408
TI  - Focus on Materials Nanoarchitectonics.

PMID- 27877410
TI  - Fabrication and textural characterization of nanoporous carbon electrodes
      embedded with CuO nanoparticles for supercapacitors.
AB  - We introduce a novel strategy of fabricating nanoporous carbons loaded with
      different amounts of CuO nanoparticles via a hard templating approach, using
      copper-containing mesoporous silica as the template and sucrose as the carbon
      source. The nature and dispersion of the CuO nanoparticles on the surface of the
      nanoporous carbons were investigated by x-ray diffraction (XRD), high-resolution
      scanning electron microscopy (HRSEM) and high-resolution transmission electron
      microscopy (HRTEM). XRD results reveal that nanoporous carbons with embedded CuO
      nanoparticles exhibit a well-ordered mesoporous structure, whereas the nitrogen
      adsorption measurements indicate the presence of excellent textural
      characteristics such as high surface area, large pore volume and uniform pore
      size distribution. The amount of CuO nanoparticles in the nanochannels of the
      nanoporous carbon could be controlled by simply varying the Si/Cu molar ratio of
      the mesoporous silica template. Morphological characterization by SEM and TEM
      reveals that high-quality CuO nanoparticles are distributed homogeneously within
      the nanoporous carbon framework. The supercapacitance behavior of the CuO-loaded
      nanoporous carbons was investigated. The material with a small amount of CuO in
      the mesochannels and high surface area affords a maximum specific capacitance of
      300 F g-1 at a 20 mV s-1 scan rate in an aqueous electrolyte solution. A
      supercapacitor containing the CuO-loaded nanoporous carbon is highly stable and
      exhibits a long cycle life with 91% specific capacitance retained after 1000
      cycles.

PMID- 27877411
TI  - Physical and mechanical properties of highly textured polycrystalline Nb4AlC3
      ceramic.
AB  - Highly textured polycrystalline Nb4AlC3 ceramic was fabricated by slip casting in
      a strong magnetic field followed by spark plasma sintering. Its Lotgering
      orientation factor was determined on the textured top and side surfaces as f(00l)
      ~1.0 and f(hk0)=0.36, respectively. This ceramic showed layered microstructure at
      the scales ranging from nanometers to millimeters. The as-prepared ceramic had
      excellent anisotropic physical properties. Along the c-axis direction, it showed
      higher hardness, bending strength, and fracture toughness of 7.0 GPa, 881 MPa and
      14.1 MPa m1/2, respectively, whereas higher values of electrical conductivity
      (0.81*106 Omega-1 m-1), thermal conductivity (21.20 W m-1 K-1) and Young's
      modulus (365 GPa) were obtained along the a- or b-axis direction.

PMID- 27877409
TI  - A bona fide two-dimensional percolation model: an insight into the optimum
      photoactivator concentration in La2/3-x Eu x Ta2O7 nanosheets.
AB  - La-Eu solid solution nanosheets La2/3-x Eu x Ta2O7 have been synthesized, and
      their photoluminescence properties have been investigated. La2/3-x Eu x Ta2O7
      nanosheets were prepared from layered perovskite compounds Li2La2/3-x Eu x Ta2O7
      as the precursors by soft chemical exfoliation reactions. Both the precursors and
      the exfoliated nanosheets exhibit a decrease in intralayer lattice parameters as
      the Eu contents increase. However, there is a discontinuity in this trend between
      the nominal Eu content ranges x<= 0.3 and x >= 0.4. This discontinuity is
      attributed to the difference in degree of TaO6 octahedra tilting for the La- and
      Eu-rich phases. La2/3-x Eu x Ta2O7 nanosheets exhibit red emission,
      characteristic of the f-f transitions in Eu3+ photoactivators. The
      photoluminescence emission can be obtained from both host and direct
      photoactivator excitation. However, photoluminescence emission through host
      excitation is much more dominant than that through direct photoactivator
      excitation, and this behavior is consistent with that of all the other rare-earth
      photoactivated nanosheets reported previously. The absolute photoluminescence
      quantum efficiency of the La2/3-x Eu x Ta2O7 nanosheets increases as the
      experimentally determined Eu contents increase up to x=0.45 and decrease above
      it. This result is in good agreement with the optimum photoactivator
      concentration expected from the percolation theory. These solid solution La2/3-x
      Eu x Ta2O7 nanosheets are excellent models for validating the theory of optimum
      photoactivator concentration in the truly two-dimensional photoactivator matrix.

PMID- 27877412
TI  - Nanoarchitectonics of a Au nanoprism array on WO3 film for synergistic
      optoelectronic response.
AB  - A layered photoelectrode consisting of a conductive indium tin oxide substrate, a
      WO3 nanocrystalline film and an array of Au nanoprisms was fabricated via a
      multistep process. Scanning electron microscopy and atomic force microscopy
      showed that the Au nanoprisms had a uniform size and shape and formed periodic
      hexagonal patterns on the WO3 film. The optical absorption of the photoelectrode
      combined the intrinsic absorption of WO3 and plasmonic absorption of Au. Using
      this photoelectrode, we investigated the effect of the Au nanoprism array on the
      optoelectronic conversion performance of the WO3 film. Photoelectrochemical
      measurement indicated that the array substantially enhanced the photocurrent in
      the WO3 film. Electrochemical impedance measurements revealed that the Schottky
      junctions formed between Au and WO3 can facilitate the separation of
      photogenerated carriers as well as the interfacial carrier transfer. In this
      study, we demonstrate that covering a semiconductor with plasmonic noble metal
      nanoparticles can improve its optoelectronic conversion efficiency.

PMID- 27877413
TI  - Thermal stability of carbon nanotubes probed by anchored tungsten nanoparticles.
AB  - The thermal stability of multiwalled carbon nanotubes (CNTs) was studied in high
      vacuum using tungsten nanoparticles as miniaturized thermal probes. The particles
      were placed on CNTs inside a high-resolution transmission electron microscope
      equipped with a scanning tunneling microscope unit. The setup allowed
      manipulating individual nanoparticles and heating individual CNTs by applying
      current to them. CNTs were found to withstand high temperatures, up to the
      melting point of 60-nm-diameter W particles (~3400 K). The dynamics of W
      particles on a hot CNT, including particle crystallization, quasimelting,
      melting, sublimation and intradiffusion, were observed in real time and recorded
      as a video. Graphite layers reel off CNTs when melted or premelted W particles
      revolve along the tube axis.

PMID- 27877414
TI  - Construction of multilayers of bare and Pd modified gold nanoclusters and their
      electrocatalytic properties for oxygen reduction.
AB  - Multilayers of gold nanoclusters (GNCs) coated with a thin Pd layer were
      constructed using GNCs modified with self-assembled monolayers (SAMs) of
      mercaptoundecanoic acid and a polyallylamine hydrochloride (PAH) multilayer
      assembly, which has been reported to act as a three-dimensional electrode. SAMs
      were removed from GNCs by electrochemical anodic decomposition and then a small
      amount of Pd was electrochemically deposited on the GNCs. The kinetics of the
      oxygen reduction reaction (ORR) on the Pd modified GNC/PAH multilayer assembly
      was studied using a rotating disk electrode, and a significant increase in the
      ORR rate was observed after Pd deposition. Electrocatalytic activities in
      alkaline and acidic solutions were compared both for the GNC multilayer electrode
      and Pd modified GNC electrode.

PMID- 27877415
TI  - Gd@C82 metallofullerenes for neutron capture therapy-fullerene solubilization by
      poly(ethylene glycol)-block-poly(2-(N, N-diethylamino)ethyl methacrylate) and
      resultant efficacy in vitro.
AB  - Poly(ethylene glycol)-block-poly(2-(N,N-diethylamino)ethyl methacrylate) (PEG-b
      PAMA) was found to solubilize fullerenes such as C60, and this technique was
      applied to metallofullerenes. Gd@C82 was easily dissolved in water in the
      presence of PEG-b-PAMA without any covalent derivatization, forming a transparent
      complex about 20-30 nm in diameter. Low cytotoxicity was confirmed in vitro.
      Neutron irradiation of cultured cells (colon-26 adenocarcinoma) with Gd@C82-PEG-b
      PAMA-complexed nanoparticles showed effective cytotoxicity, indicating the
      effective emission of gamma rays and internal conversion electrons produced from
      the neutron capture reaction of Gd. This result suggests a potentially valuable
      approach to gadolinium-based neutron capture therapy.

PMID- 27877416
TI  - Dynamic culture substrate that captures a specific extracellular matrix protein
      in response to light.
AB  - The development of methods for the off-on switching of immobilization or
      presentation of cell-adhesive peptides and proteins during cell culture is
      important because such surfaces are useful for the analysis of the dynamic
      processes of cell adhesion and migration. This paper describes a chemically
      functionalized gold substrate that captures a genetically tagged extracellular
      matrix protein in response to light. The substrate was composed of mixed self
      assembled monolayers (SAMs) of three disulfide compounds containing (i) a
      photocleavable poly(ethylene glycol) (PEG), (ii) nitrilotriacetic acid (NTA) and
      (iii) hepta(ethylene glycol) (EG7). Although the NTA group has an intrinsic high
      affinity for oligohistidine tag (His-tag) sequences in its Ni2+-ion complex, the
      interaction was suppressed by the steric hindrance of coexisting PEG on the
      substrate surface. Upon photoirradiation of the substrate to release the PEG
      chain from the surface, this interaction became possible and hence the protein
      was captured at the irradiated regions, while keeping the non-specific adsorption
      of non-His-tagged proteins blocked by the EG7 underbrush. In this way, we
      selectively immobilized a His-tagged fibronectin fragment (FNIII7-10) to the
      irradiated regions. In contrast, when bovine serum albumin-a major serum protein
      was added as a non-His-tagged protein, the surface did not permit its capture,
      with or without irradiation. In agreement with these results, cells were
      selectively attached to the irradiated patterns only when a His-tagged FNIII7-10
      was added to the medium. These results indicate that the present method is useful
      for studying the cellular behavior on the specific extracellular matrix protein
      in cell-culturing environments.

PMID- 27877417
TI  - Surface design with self-heating smart polymers for on-off switchable traps.
AB  - We have developed a novel self-heating, temperature-responsive chromatography
      system for the effective separation of biomolecules. Temperature-responsive
      poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide), poly(NIPAAm-co-HMAAm),
      was covalently grafted onto the surface of magnetite/silica composites as 'on
      off' switchable surface traps. The lower critical solution temperature (LCST) of
      the poly(NIPAAm-co-HMAAm)s was controlled from 35 to 55  degrees C by varying the
      HMAAm content. Using the heat generated by magnetic particles in an alternating
      magnetic field (AMF) we were able to induce the hydrophilic to hydrophobic phase
      separation of the grafted temperature-responsive polymers. To assess the
      feasibility of the poly(NIPAAm-co-HMAAm)-grafted magnetite/silica particles as
      the stationary phase for chromatography, we packed the particles into the glass
      column of a liquid chromatography system and analyzed the elusion profiles for
      steroids. The retention time for hydrophobic steroids markedly increased in the
      AMF, because the hydrophobic interaction was enhanced via self-heating of the
      grafted magnetite/silica particles, and this effect could be controlled by
      changing the AMF irradiation time. Turning off the AMF shortened the total
      analysis time for steroids. The proposed system is useful for separating
      bioactive compounds because their elution profiles can be easily controlled by an
      AMF.

PMID- 27877418
TI  - Local distortions in multiferroic BiMnO3 as a function of doping.
AB  - The structure of doped BiMnO3 was studied using synchrotron x-ray powder
      diffraction. The dopants included isovalent magnetic and non-magnetic ions in the
      magnetic Mn sublattice (BiMn1-xMx O3 with M=Cr, Fe and Ga), isovalent ions in the
      Bi sublattice (Bi0.9La0.1MnO3) and isovalent self-dopants (Bi0.95MnO2.925). The
      results indicate that at low doping levels, the orbitally ordered structure
      (C2/c(I)) of BiMnO3 persists with strong Jahn-Teller distortions of two Mn1O6 and
      Mn2O6 octahedra (e.g. in BiMn0.95Ga0.05O3 and Bi0.95MnO2.925); the distortion
      parameters of the Mn1O6 and Mn2O6 octahedra are noticeably smaller in
      BiMn0.95Ga0.05O3 and Bi0.95MnO2.925 than in BiMnO3. At higher doping levels, the
      orbitally disordered structure (C2/c(II)) of BiMnO3 is realized with almost
      identical Mn-O bond lengths for one of the Mn1O6 or Mn2O6 octahedra (e.g. in
      BiMn0.85Cr0.15O3 and BiMn0.85Fe0.15O3). BiMn0.85Fe0.15O3 shows some anomalies in
      the distortion of the MnO6 octahedra and in the magnetic properties. Rather
      strong Jahn-Teller distortions were found for both the Mn1O6 and Mn2O6 octahedra
      in Bi0.9La0.1MnO3. The Mn1O6 and Mn2O6 octahedra were compressed along one
      direction in Bi0.9La0.1MnO3 whereas the octahedra were elongated in BiMnO3.
      Magnetic measurements indicate that Bi0.9La0.1MnO3 adopts the orbitally
      disordered C2/c(II) structure. The orbitally ordered state of BiMnO3 was found to
      be very fragile to any type of doping. However, as long as the orbitally ordered
      phase persists, the ferromagnetic transition temperature remains almost the same.

PMID- 27877419
TI  - Nanoscale synthesis and characterization of graphene-based objects.
AB  - Graphene-based nano-objects such as nanotrenches, nanowires, nanobelts and
      nanoscale superstructures have been grown by surface segregation and
      precipitation on carbon-doped mono- and polycrystalline nickel substrates in
      ultrahigh vacuum. The dominant morphologies of the nano-objects were nanowire and
      nanosheet. Nucleation of graphene sheets occurred at surface defects such as step
      edges and resulted in the directional growth of nanowires. Surface analysis by
      scanning tunneling microscopy (STM) has clarified the structure and functionality
      of the novel nano-objects at atomic resolution. Nanobelts were detected
      consisting of bilayer graphene sheets with a nanoscale width and a length of
      several microns. Moire patterns and one-dimensional reconstruction were observed
      on multilayer graphite terraces. As a useful functionality, application to
      repairable high-resolution STM probes is demonstrated.

PMID- 27877420
TI  - Metal-assisted chemical etching using sputtered gold: a simple route to black
      silicon.
AB  - We report an accessible and simple method of producing 'black silicon' with
      aspect ratios as high as 8 using common laboratory equipment. Gold was sputtered
      to a thickness of 8 nm using a low-vacuum sputter coater. The structures were
      etched into silicon substrates using an aqueous H2O2/HF solution, and the gold
      was then removed using aqua regia. Ultrasonication was necessary to produce
      columnar structures, and an etch time of 24 min gave a velvety, non-reflective
      surface. The surface features after 24 min etching were uniformly microstructured
      over an area of square centimetres.

PMID- 27877421
TI  - Electrically tunable sign of capacitance in planar W-doped vanadium dioxide micro
      switches.
AB  - Negative capacitance (NC) in a planar W-doped VO2 micro-switch was observed at
      room temperature in the low-frequency range 1 kHz-10 MHz. The capacitance changed
      from positive to negative values as the W-doped VO2 active layer switched from
      semiconducting to metallic state under applied voltage. In addition, a
      capacitance-voltage hysteresis was observed as the applied voltage was cycled
      from -35 to 35 V. These observations suggest that NC results from the increase of
      the electrically induced conductivity in the active layer. This NC phenomenon
      could be exploited in advanced multifunctional devices including ultrafast
      switches, field-effect transistors and memcapacitive systems.

PMID- 27877422
TI  - Control of the pore architecture in three-dimensional hydroxyapatite-reinforced
      hydrogel scaffolds.
AB  - Hydrogels (gellan or agarose) reinforced with nanocrystalline carbonated
      hydroxyapatite (nCHA) were prepared by the GELPOR3D technique. This simple method
      is characterized by compositional flexibility; it does not require expensive
      equipment, thermal treatment, or aggressive or toxic solvents, and yields a three
      dimensional (3D) network of interconnected pores 300-900 MUm in size. In
      addition, an interconnected porosity is generated, yielding a hierarchical porous
      architecture from the macro to the molecular scale. This porosity depends on both
      the drying/preservation technology (freeze drying or oven drying at 37 ?C) and on
      the content and microstructure of the reinforcing ceramic. For freeze-dried
      samples, the porosities were approximately 30, 66 and below 3% for pore sizes of
      600-900 MUm, 100-200 MUm and 50-100 nm, respectively. The pore structure depends
      much on the ceramic content, so that higher contents lead to the disappearance of
      the characteristic honeycomb structure observed in low-ceramic scaffolds and to a
      lower fraction of the 100-200-MUm-sized pores. The nature of the hydrogel did not
      affect the pore size distribution but was crucial for the behavior of the
      scaffolds in a hydrated medium: gellan-containing scaffolds showed a higher
      swelling degree owing to the presence of more hydrophilic groups.

PMID- 27877423
TI  - Acoustic emission monitoring of activation behavior of LaNi5 hydrogen storage
      alloy.
AB  - The acoustic emission technique is proposed for assessing the irreversible
      phenomena occurring during hydrogen absorption/desorption cycling in LaNi5. In
      particular, we have studied, through a parametric analysis of in situ detected
      signals, the correlation between acoustic emission (AE) parameters and the
      processes occurring during the activation of an intermetallic compound. Decreases
      in the number and amplitude of AE signals suggest that pulverization due to
      hydrogen loading involves progressively smaller volumes of material as the number
      of cycles increases. This conclusion is confirmed by electron microscopy
      observations and particle size distribution measurements.

PMID- 27877424
TI  - Block-copolymer-assisted synthesis of hydroxyapatite nanoparticles with high
      surface area and uniform size.
AB  - We report the synthesis of hydroxyapatite nanoparticles (HANPs) by the
      coprecipitation method using calcium D-gluconate and potassium hydrogen phosphate
      as the sources of calcium and phosphate ions, respectively, and the triblock
      copolymer F127 as a stabilizer. The HANPs were characterized using scanning
      electron microscopy, x-ray diffraction, and nitrogen adsorption/desorption
      isotherms. Removal of F127 by solvent extraction or calcination alters the
      structure of HANPs. The solvent-extracted HANPs were single crystals with their
      <001> axis oriented along the rod axis of the HANP, whereas the calcined HANPs
      contained two crystal phases that resulted in a spherical morphology. The
      calcined HANPs had much higher surface area (127 m2 g-1) than the solvent
      extracted HANPs (44 m2 g-1).

PMID- 27877426
TI  - Focus on Combinatorial Materials Science.

PMID- 27877425
TI  - Biopolymer-based nanocomposites: effect of lignin acetylation in cellulose
      triacetate films.
AB  - We have prepared all-biopolymer nanocomposite films using lignin as a filler and
      cellulose triacetate (CTA) as a polymer matrix, and characterized them by several
      analytical methods. Three types of lignin were tested: organosolv, hydrolytic and
      kraft, with or without acetylation. They were used in the form of nanoparticles
      incorporated at 1 wt% in CTA. Self-supported films were prepared by vapor-induced
      phase separation at controlled temperature (35-55  degrees C) and relative
      humidity (10-70%). The efficiency of acetylation of each type of lignin was
      studied and discussed, as well as its effects on film structure, homogeneity and
      mechanical properties. The obtained results are explained in terms of
      intermolecular filler-matrix interaction at the nanometer scale, for which the
      highest mechanical resistance was reached using hydrolytic lignin in the
      nanocomposite.

PMID- 27877428
TI  - High-throughput characterization of film thickness in thin film materials
      libraries by digital holographic microscopy.
AB  - A high-throughput characterization technique based on digital holography for
      mapping film thickness in thin-film materials libraries was developed. Digital
      holographic microscopy is used for fully automatic measurements of the thickness
      of patterned films with nanometer resolution. The method has several significant
      advantages over conventional stylus profilometry: it is contactless and fast,
      substrate bending is compensated, and the experimental setup is simple. Patterned
      films prepared by different combinatorial thin-film approaches were characterized
      to investigate and demonstrate this method. The results show that this technique
      is valuable for the quick, reliable and high-throughput determination of the film
      thickness distribution in combinatorial materials research. Importantly, it can
      also be applied to thin films that have been structured by shadow masking.

PMID- 27877427
TI  - High-throughput technology for novel SO2 oxidation catalysts.
AB  - We review the state of the art and explain the need for better SO2 oxidation
      catalysts for the production of sulfuric acid. A high-throughput technology has
      been developed for the study of potential catalysts in the oxidation of SO2 to
      SO3. High-throughput methods are reviewed and the problems encountered with their
      adaptation to the corrosive conditions of SO2 oxidation are described. We show
      that while emissivity-corrected infrared thermography (ecIRT) can be used for
      primary screening, it is prone to errors because of the large variations in the
      emissivity of the catalyst surface. UV-visible (UV-Vis) spectrometry was selected
      instead as a reliable analysis method of monitoring the SO2 conversion.
      Installing plain sugar absorbents at reactor outlets proved valuable for the
      detection and quantitative removal of SO3 from the product gas before the UV-Vis
      analysis. We also overview some elements used for prescreening and those
      remaining after the screening of the first catalyst generations.

PMID- 27877429
TI  - A novel high-throughput fatigue testing method for metallic thin films.
AB  - Thin films are used in a wide variety of computing and communication applications
      although their fatigue behavior and its dependence on alloying elements are not
      very well known. In this paper, we present an experimental implementation of a
      novel high-throughput fatigue testing method for metallic thin films. The
      methodology uses the fact that the surface strain amplitude of a vibrating
      cantilever decreases linearly from the fixed end to the free end. Therefore, a
      thin film attached to a vibrating cantilever will experience a gradient of strain
      and corresponding stress amplitudes along the cantilever. Each cantilever can be
      used to extract a lifetime diagram by measuring the fatigue-induced damage front
      that progresses along the cantilever during up to 108 load cycles.

PMID- 27877430
TI  - Charge-discharge properties of a layered-type Li(Ni,Co,Ti)O2 powder library.
AB  - A powder library of layered Li(Ni,Co,Ti)O2 (Ni <= 0.8, Ti <= 0.2) compounds was
      prepared by electrostatic spray deposition. From powder x-ray diffraction
      patterns, most of the powder library sintered at 700 ?C was indexed as a single
      phase belonging to the space group R[Formula: see text]m. These results were
      almost identical to those obtained from a study by combinatorial exploration. We
      investigated the charge-discharge characteristics of the Li(Ni,Co,Ti)O2 powder
      library in a voltage range from 4.2 to 2.8 V at 1 C and found favorable cycling
      properties in the LiNi x Co0.9-x Ti0.1O2 (0 <=x <= 0.6) compounds.

PMID- 27877431
TI  - High-throughput CW-IR laser deposition and laser microscope imaging of binary
      ionic liquids in vacuum.
AB  - A combinatorial library of binary mixtures of ionic liquids with various mixing
      ratios was fabricated on a single sapphire substrate using the composition-spread
      technique combined with a continuous-wave infrared (CW-IR) laser deposition
      method; the mixtures were condensed in the form of micro-scale droplets. The
      mixing ratio within the droplets was examined by Raman spectroscopy. The contact
      angle of the droplets was found to systematically vary with the mixing ratio.
      Their thermal behavior was characterized with an ultrahigh-vacuum laser
      microscope, revealing the dependence of the evaporation rate on the mixing ratio.

PMID- 27877432
TI  - Combinatorial synthesis of phosphors using arc-imaging furnace.
AB  - We have applied a novel 'melt synthesis technique' rather than a conventional
      solid-state reaction to rapidly synthesize phosphor materials. During a
      synthesis, the mixture of oxides or their precursors is melted by light pulses
      (10-60 s) in an arc-imaging furnace on a water-cooled copper hearth to form a
      globule of 1-5 mm diameter, which is then rapidly cooled by turning off the
      light. Using this method, we synthesized several phosphor compounds including
      Y3Al5O12:Ce(YAG) and SrAl2O4:Eu,Dy. Complex phosphor oxides are difficult to
      produce by conventional solid-state reaction techniques because of the slow
      reaction rates among solid oxides; as a result, the oxides form homogeneous
      compounds or solid solutions. On the other hand, melt reactions are very fast (10
      60 s) and result in homogeneous compounds owing to rapid diffusion and mixing in
      the liquid phase. Therefore, melt synthesis techniques are suitable for preparing
      multi component homogeneous compounds and solid solutions.

PMID- 27877433
TI  - Modular high-throughput test stand for versatile screening of thin-film materials
      libraries.
AB  - Versatile high-throughput characterization tools are required for the development
      of new materials using combinatorial techniques. Here, we describe a modular,
      high-throughput test stand for the screening of thin-film materials libraries,
      which can carry out automated electrical, magnetic and magnetoresistance
      measurements in the temperature range of -40 to 300  degrees C. As a proof of
      concept, we measured the temperature-dependent resistance of Fe-Pd-Mn
      ferromagnetic shape-memory alloy materials libraries, revealing reversible
      martensitic transformations and the associated transformation temperatures.
      Magneto-optical screening measurements of a materials library identify
      ferromagnetic samples, whereas resistivity maps support the discovery of new
      phases. A distance sensor in the same setup allows stress measurements in
      materials libraries deposited on cantilever arrays. A combination of these
      methods offers a fast and reliable high-throughput characterization technology
      for searching for new materials. Using this approach, a composition region has
      been identified in the Fe-Pd-Mn system that combines ferromagnetism and
      martensitic transformation.

PMID- 27877434
TI  - A combinatorial characterization scheme for high-throughput investigations of
      hydrogen storage materials.
AB  - In order to increase measurement throughput, a characterization scheme has been
      developed that accurately measures the hydrogen storage properties of materials
      in quantities ranging from 10 ng to 1 g. Initial identification of promising
      materials is realized by rapidly screening thin-film composition spread and
      thickness wedge samples using normalized IR emissivity imaging. The hydrogen
      storage properties of promising samples are confirmed through measurements on
      single-composition films with high-sensitivity (resolution <0.3 MUg) Sievert's
      type apparatus. For selected samples, larger quantities of up to ~100 mg may be
      prepared and their (de)hydrogenation and micro-structural properties probed via
      parallel in situ Raman spectroscopy. Final confirmation of the hydrogen storage
      properties is obtained on ~1 g powder samples using a combined Raman
      spectroscopy/Sievert's apparatus.

PMID- 27877435
TI  - Combinatorial investigation of Fe-B thin-film nanocomposites.
AB  - Combinatorial magnetron sputter deposition from elemental targets was used to
      create Fe-B composition spread type thin film materials libraries on thermally
      oxidized 4-in. Si wafers. The materials libraries consisting of wedge-type
      multilayer thin films were annealed at 500 or 700  degrees C to transform the
      multilayers into multiphase alloys. The libraries were characterized by nuclear
      reaction analysis, Rutherford backscattering, nanoindentation, vibrating sample
      magnetometry, x-ray diffraction (XRD) and transmission electron microscopy (TEM).
      Young's modulus and hardness values were related to the annealing parameters,
      structure and composition of the films. The magnetic properties of the films were
      improved by annealing in a H2 atmosphere, showing a more than tenfold decrease in
      the coercive field values in comparison to those of the vacuum-annealed films.
      The hardness values increased from 8 to 18 GPa when the annealing temperature was
      increased from 500 to 700  degrees C. The appearance of Fe2B phases, as revealed
      by XRD and TEM, had a significant effect on the mechanical properties of the
      films.

PMID- 27877436
TI  - Screening of metal flux for SiC solution growth by a thin-film combinatorial
      method.
AB  - 4H-SiC is a wide-bandgap semiconductor with potential applications in power
      devices. The lack of a liquid phase in SiC hinders conventional crystal growth
      from the melt; consequently, SiC wafers still have low quality and are nearly 100
      times more expensive than Si wafers. To take advantage of the solution growth for
      improving the quality and reducing the cost of SiC, Ni addition to Si-Ti flux has
      been investigated. A combinatorial approach was employed to accelerate the
      screening of metal flux for the SiC solution growth.

PMID- 27877437
TI  - Development of compact CW-IR laser deposition system for high-throughput growth
      of organic single crystals.
AB  - We developed a compact continuous-wave infrared (CW-IR) laser deposition system
      for the high-throughput growth of organic single crystals. In this system, two CW
      IR lasers are used for the sample heating and thermal evaporation of materials.
      The CW-IR laser heating is simple and allows good control of the deposition rate
      and growth temperature, in response to the on/off laser switching. Six samples
      can be loaded simultaneously in a chamber, which allows one-by-one sequential
      deposition for high-throughput experiments, without breaking the vacuum. Using
      this setup, we studied the effect of ionic liquids on the growth of C60 crystals
      in vacuum.

PMID- 27877438
TI  - Chemiluminescence analyzer of NO x as a high-throughput screening tool in
      selective catalytic reduction of NO.
AB  - A chemiluminescence-based analyzer of NO x gas species has been applied for high
      throughput screening of a library of catalytic materials. The applicability of
      the commercial NO x analyzer as a rapid screening tool was evaluated using
      selective catalytic reduction of NO gas. A library of 60 binary alloys composed
      of Pt and Co, Zr, La, Ce, Fe or W on Al2O3 substrate was tested for the
      efficiency of NO x removal using a home-built 64-channel parallel and sequential
      tubular reactor. The NO x concentrations measured by the NO x analyzer agreed
      well with the results obtained using micro gas chromatography for a reference
      catalyst consisting of 1 wt% Pt on gamma-Al2O3. Most alloys showed high
      efficiency at 275  degrees C, which is typical of Pt-based catalysts for
      selective catalytic reduction of NO. The screening with NO x analyzer allowed to
      select Pt-Ce(X) (X=1-3) and Pt-Fe(2) as the optimal catalysts for NO x removal:
      73% NO x conversion was achieved with the Pt-Fe(2) alloy, which was much better
      than the results for the reference catalyst and the other library alloys. This
      study demonstrates a sequential high-throughput method of practical evaluation of
      catalysts for the selective reduction of NO.

PMID- 27877439
TI  - Monodisperse colloidal spheres for (Y,Eu)2O3 red-emitting phosphors:
      establishment of processing window and size-dependent luminescence behavior.
AB  - The urea-based homogeneous precipitation method was introduced in the preparation
      of monodisperse colloidal spheres for (Y0.95Eu0.05)2O3 red-emitting phosphors,
      and the processing window was defined. Particle size and shape are significantly
      affected by the ion concentration and the urea/RE3+ molar ratio R
      (RE3+=Y3++Eu3+). A low ion concentration is beneficial in forming monodisperse
      spheres and extending their formation domain. Increasing R results in a gradual
      change in the composition of spherical particles from the core-shell
      Eu(OH)CO3@Y(OH)CO3 structure to a homogeneous solid solution, thereby
      significantly lowering the calcination temperature at which precursors convert to
      oxides. Upon UV excitation into the charge-transfer band at 254 nm, the uniform
      phosphor spheres of (Y0.95Eu0.05)2O3 exhibit typical red emissions at 613 nm; the
      emission is stronger from larger particles mainly because of their smaller
      surface area. Both the luminescence intensity and quantum efficiency of the oxide
      phosphors increase with elevated calcination temperatures. The spherical shape
      and excellent dispersion of the precursor particles (~450 nm in diameter) have
      been well retained after calcination at 1000 ?C for 4 h, and the resultant oxide
      phosphors exhibit external and internal quantum efficiencies of 50 and 82%,
      respectively.

PMID- 27877440
TI  - Physical characterization of functionalized spider silk: electronic and sensing
      properties.
AB  - This work explores functional, fundamental and applied aspects of naturally
      harvested spider silk fibers. Natural silk is a protein polymer where different
      amino acids control the physical properties of fibroin bundles, producing, for
      example, combinations of beta-sheet (crystalline) and amorphous (helical)
      structural regions. This complexity presents opportunities for functional
      modification to obtain new types of material properties. Electrical conductivity
      is the starting point of this investigation, where the insulating nature of neat
      silk under ambient conditions is described first. Modification of the
      conductivity by humidity, exposure to polar solvents, iodine doping, pyrolization
      and deposition of a thin metallic film are explored next. The conductivity
      increases exponentially with relative humidity and/or solvent, whereas only an
      incremental increase occurs after iodine doping. In contrast, iodine doping,
      optimal at 70  degrees C, has a strong effect on the morphology of silk bundles
      (increasing their size), on the process of pyrolization (suppressing mass loss
      rates) and on the resulting carbonized fiber structure (that becomes more robust
      against bending and strain). The effects of iodine doping and other functional
      parameters (vacuum and thin film coating) motivated an investigation with magic
      angle spinning nuclear magnetic resonance (MAS-NMR) to monitor doping-induced
      changes in the amino acid-protein backbone signature. MAS-NMR revealed a moderate
      effect of iodine on the helical and beta-sheet structures, and a lesser effect of
      gold sputtering. The effects of iodine doping were further probed by Fourier
      transform infrared (FTIR) spectroscopy, revealing a partial transformation of
      beta-sheet-to-amorphous constituency. A model is proposed, based on the findings
      from the MAS-NMR and FTIR, which involves iodine-induced changes in the silk
      fibroin bundle environment that can account for the altered physical properties.
      Finally, proof-of-concept applications of functionalized spider silk are
      presented for thermoelectric (Seebeck) effects and incandescence in iodine-doped
      pyrolized silk fibers, and metallic conductivity and flexibility of micron-sized
      gold-sputtered silk fibers. In the latter case, we demonstrate the application of
      gold-sputtered neat spider silk to make four-terminal, flexible, ohmic contacts
      to organic superconductor samples.

PMID- 27877441
TI  - Effect of sintering temperature on optical properties and microstructure of
      translucent zirconia prepared by high-pressure spark plasma sintering.
AB  - Aiming to characterize the effect of sintering temperature on transparency of
      zirconia, we have evaluated the optical properties and microstructure of
      translucent cubic zirconia prepared by high-pressure spark plasma sintering (SPS)
      at 1000-1200 ?C. Color centers (oxygen vacancies with trapped electrons) and
      residual pores were primary defects in the samples. In SPS samples, the total
      forward transmittance and in-line transmittance are mainly affected by color
      centers with a limited contribution from residual pores; in contrast, the changes
      in reflectance are only related to the porosity. The amounts of color centers and
      residual pores increase with sintering temperature that reduces the total forward
      and in-line transmittance of the as-sintered zirconia. Annealing in oxidizing
      atmosphere improves the total forward and in-line transmittance. During the
      annealing, the concentration of color centers decreases but the porosity
      increases.

PMID- 27877442
TI  - Multifunctional ZnO/Nylon 6 nanofiber mats by an electrospinning-electrospraying
      hybrid process for use in protective applications.
AB  - ZnO/Nylon 6 nanofiber mats were prepared by an electrospinning-electrospraying
      hybrid process in which ZnO nanoparticles were dispersed on the surface of Nylon
      6 nanofibers without becoming completely embedded. The prepared ZnO/Nylon 6
      nanofiber mats were evaluated for their abilities to kill bacteria or inhibit
      their growth and to catalytically detoxify chemicals. Results showed that these
      ZnO/Nylon 6 nanofiber mats had excellent antibacterial efficiency (99.99%)
      against both the Gram-negative Escherichia coli and Gram-positive Bacillus cereus
      bacteria. In addition, they exhibited good detoxifying efficiency (95%) against
      paraoxon, a simulant of highly toxic chemicals. ZnO/Nylon 6 nanofiber mats were
      also deposited onto nylon/cotton woven fabrics and the nanofiber mats did not
      significantly affect the moisture vapor transmission rates and air permeability
      values of the fabrics. Therefore, ZnO/Nylon 6 nanofiber mats prepared by the
      electrospinning-electrospraying hybrid process are promising material candidates
      for protective applications.

PMID- 27877443
TI  - Electrodeposition of zinc-silica composite coatings: challenges in incorporating
      functionalized silica particles into a zinc matrix.
AB  - Zinc is a well-known sacrificial coating material for iron and co-deposition of
      suitable particles is of interest for further improving its corrosion protection
      performance. However, incorporation of particles that are well dispersible in
      aqueous electrolytes, such as silica particles, is extremely difficult. Here, we
      report a detailed study of Zn-SiO2 nanocomposite coatings deposited from a zinc
      sulfate solution at pH 3. The effect of functionalization of the silica particles
      on the electro-codeposition was investigated. The best incorporation was achieved
      for particles modified with SiO2-SH, dithiooxamide or cysteamine; these particles
      have functional groups that can strongly interact with zinc and therefore
      incorporate well into the metal matrix. Other modifications (SiO2-NH3+, SiO2-Cl
      and N,N-dimethyldodecylamine) of the silica particles lead to adsorption and
      entrapment only.

PMID- 27877444
TI  - Hybrid nanocomposite based on cellulose and tin oxide: growth, structure, tensile
      and electrical characteristics.
AB  - A highly flexible nanocomposite was developed by coating a regenerated cellulose
      film with a thin layer of tin oxide (SnO2) by liquid-phase deposition. Tin oxide
      was crystallized in solution and formed nanocrystal coatings on regenerated
      cellulose. The nanocrystalline layers did not exfoliate from cellulose.
      Transmission electron microscopy and energy dispersive x-ray spectroscopy suggest
      that SnO2 was not only deposited over the cellulose surface, but also nucleated
      and grew inside the cellulose film. Current-voltage characteristics of the
      nanocomposite revealed that its electrical resistivity decreases with deposition
      time, with the lowest value obtained for 24 h of deposition. The cellulose-SnO2
      hybrid nanocomposite can be used for biodegradable and disposable chemical,
      humidity and biosensors.

PMID- 27877445
TI  - S-Nitroso-N-acetyl-D-penicillamine covalently linked to polydimethylsiloxane
      (SNAP-PDMS) for use as a controlled photoinitiated nitric oxide release polymer.
AB  - Nitric oxide (NO) plays a critical role in the regulation of a wide variety of
      physiological processes. It is a potent inhibitor of platelet adhesion and
      aggregation, inhibits bacterial adhesion and proliferation, is implicated in
      mediating the inflammatory response toward implanted devices, plays a role in
      tumor growth and proliferation, and is a neurotransmitter. Herein, we describe
      the synthesis and NO-release properties of a modified polydimethylsiloxane that
      contains S-nitroso-N-acetyl-D-penicillamine covalently attached to the cross
      linking agent (SNAP-DMS). Light from a C503B-BAN-CY0C0461 light-emitting diode
      (470 nm) was used as an external trigger to allow precise control over level and
      duration of NO release ranging from a surface flux of zero to approximately
      3.5*10-10 mol cm-2 min-1. SNAP-PDMS films stored in the dark released NO after
      297 days, indicating the long-term stability of SNAP-PDMS.

PMID- 27877446
TI  - beta-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier
      physicochemical interactions.
AB  - Calcium phosphate bone substitute materials can be loaded with active substances
      for in situ, targeted drug administration. In this study, porous beta-TCP pellets
      were investigated as an anti-inflammatory drug carrier. Porous beta-TCP pellets
      were impregnated with an ethanolic solution of ibuprofen. The effects of contact
      time and concentration of ibuprofen solution on drug adsorption were studied. The
      ibuprofen adsorption equilibrium time was found to be one hour. The adsorption
      isotherms fitted to the Freundlich model, suggesting that the interaction between
      ibuprofen and beta-TCP is weak. The physicochemical characterizations of loaded
      pellets confirmed that the reversible physisorption of ibuprofen on beta-TCP
      pellets is due to Van der Waals forces, and this property was associated with the
      100% ibuprofen release.

PMID- 27877447
TI  - High-pressure high-temperature synthesis and structure of alpha-tetragonal boron.
AB  - Microcrystals of alpha-tetragonal (alpha-t) boron with unit cell parameters
      a=9.05077(6) and c=5.13409(6) A and measured density 2.16-2.22 g cm-3 were
      obtained by pyrolysis of decaborane B10H14 at pressures of 8-9 GPa and
      temperatures of 1100-1600 ?C. The crystal structure is in good agreement with the
      model proposed by Hoard et al (1958 J. Am. Chem. Soc.80 4507). However, compared
      to the original model, we found small deformations of icosahedra and changes in
      the interatomic distances within the unit cell of the synthesized alpha-t boron.

PMID- 27877449
TI  - Focus on New Materials Mimicking Nature.

PMID- 27877448
TI  - Delayed onset of photochromism in molybdenum oxide films caused by photoinduced
      defect formation.
AB  - We report the photochromic properties of amorphous MoO3 films deposited by dc
      sputtering with different O2 flow rates. The kinetics of film coloration under UV
      light irradiation is determined using optical transmission spectroscopy. Changes
      in the absorbance and refractive index were derived from the analysis of
      transmittance spectra. The absorbance spectra exhibited a growing broad peak
      centered around 830 nm, which was induced by the UV irradiation. In the early
      stages of irradiation, the absorbance of the films did not change but their
      refractive indices did change. This induction time was correlated with the O2
      partial pressure during the film deposition, which was controlled by the O2 flow
      rate. The origins of this observation are discussed.

PMID- 27877450
TI  - The Portevin-Le Chatelier effect: a review of experimental findings.
AB  - The Portevin-Le Chatelier (PLC) effect manifests itself as an unstable plastic
      flow during tensile tests of some dilute alloys under certain regimes of strain
      rate and temperature. The plastic strain becomes localized in the form of bands
      which move along a specimen gauge in various ways as the PLC effect occurs.
      Because the localization of strain causes degradation of the inherent structural
      properties and surface quality of materials, understanding the effect is crucial
      for the effective use of alloys. The characteristic behaviors of localized strain
      bands and techniques commonly used to study the PLC effect are summarized in this
      review. A brief overview of experimental findings, the effect of material
      properties and test parameters on the PLC effect, and some discussion on the
      mechanisms of the effect are included. Tests for predicting the early failure of
      structural materials due to embrittlement induced by the PLC effect are also
      discussed.

PMID- 27877451
TI  - Porous ceramics mimicking nature-preparation and properties of microstructures
      with unidirectionally oriented pores.
AB  - Porous ceramics with unidirectionally oriented pores have been prepared by
      various methods such as anodic oxidation, templating using wood, unidirectional
      solidification, extrusion, etc. The templating method directly replicates the
      porous microstructure of wood to prepare porous ceramics, whereas the extrusion
      method mimics the microstructures of tracheids and xylems in trees. These two
      methods are therefore the main focus of this review as they provide good examples
      of the preparation of functional porous ceramics with properties replicating
      nature. The well-oriented cylindrical through-hole pores prepared by the
      extrusion method using fibers as the pore formers provide excellent permeability
      together with high mechanical strength. Examples of applications of these porous
      ceramics are given, including their excellent capillary lift of over 1 m height
      which could be used to counteract urban heat island phenomena, and other
      interesting properties arising from anisotropic unidirectional porous structures.

PMID- 27877452
TI  - Monohydrocalcite: a promising remediation material for hazardous anions.
AB  - The formation conditions, solubility and stability of monohydrocalcite (MHC,
      CaCO3.H2O), as well as sorption behaviors of toxic anions on MHC, are reviewed to
      evaluate MHC as a remediation material for hazardous oxyanions. MHC is a rare
      mineral in geological settings that occurs in recent sediments in saline lakes.
      Water temperature does not seem to be an important factor for MHC formation. The
      pH of lake water is usually higher than 8 and the Mg/Ca ratio exceeds 4. MHC
      synthesis experiments as a function of time indicate that MHC is formed from
      amorphous calcium carbonate and transforms to calcite and/or aragonite. Most
      studies show that MHC forms from solutions containing Mg, which inhibits the
      formation of stable calcium carbonates. The solubility of MHC is higher than
      those of calcite, aragonite and vaterite, but lower than those of ikaite and
      amorphous calcium carbonate at ambient temperature. The solubility of MHC
      decreases with temperature. MHC is unstable and readily transforms to calcite or
      aragonite. The transformation consists of the dissolution of MHC and the
      subsequent formation of stable phases from the solution. The rate-limiting steps
      of the transformation of MHC are the nucleation and growth of stable crystalline
      phases. Natural occurrences indicate that certain additives, particularly PO4 and
      Mg, stabilize MHC. Laboratory studies confirm that a small amount of PO4 in
      solution (>30 MUM) can significantly inhibit the transformation of MHC. MHC has a
      higher sorption capacity for PO4 than calcite and aragonite. The modes of PO4
      uptake are adsorption on the MHC surface at moderate phosphate concentrations and
      precipitation of secondary calcium phosphate minerals at higher concentrations.
      Arsenate is most likely removed from the solution during the transformation of
      MHC. The proposed sorption mechanism of arsenate is coprecipitation during
      crystallization of aragonite. The arsenic sorption capacity by MHC is
      significantly higher than simple adsorption on calcite.

PMID- 27877453
TI  - Assembly of cells and vesicles for organ engineering.
AB  - The development of materials and technologies for the assembly of cells and/or
      vesicles is a key for the next generation of tissue engineering. Since the
      introduction of the tissue engineering concept in 1993, various types of
      scaffolds have been developed for the regeneration of connective tissues in vitro
      and in vivo. Cartilage, bone and skin have been successfully regenerated in
      vitro, and these regenerated tissues have been applied clinically. However,
      organs such as the liver and pancreas constitute numerous cell types, contain
      small amounts of extracellular matrix, and are highly vascularized. Therefore,
      organ engineering will require the assembly of cells and/or vesicles. In
      particular, adhesion between cells/vesicles will be required for regeneration of
      organs in vitro. This review introduces and discusses the key technologies and
      materials for the assembly of cells/vesicles for organ regeneration.

PMID- 27877454
TI  - Tunable structural color in organisms and photonic materials for design of
      bioinspired materials.
AB  - In this paper, the key topics of tunable structural color in biology and material
      science are overviewed. Color in biology is considered for selected groups of
      tropical fish, octopus, squid and beetle. It is caused by nanoplates in
      iridophores and varies with their spacing, tilting angle and refractive index.
      These examples may provide valuable hints for the bioinspired design of photonic
      materials. 1D multilayer films and 3D colloidal crystals with tunable structural
      color are overviewed from the viewpoint of advanced materials. The tunability of
      structural color by swelling and strain is demonstrated on an example of opal
      composites.

PMID- 27877455
TI  - Geomaterials: their application to environmental remediation.
AB  - Geomaterials are materials inspired by geological systems originating from the
      billion years long history of the Earth. This article reviews three important
      classes of geomaterials. The first one is smectites-layered silicates with a
      cation-exchange capacity. Smectites are useful for removing pollutants and as
      intercalation compounds, catalysts and polymer nanocomposites. The second class
      is layered double hydroxides (LDHs). They have an anion-exchange capacity and are
      used as catalysts, catalyst precursors, sorbents and scavengers for halogens. The
      third class of geomaterials is zeolites-microporous materials with a cation
      exchange capacity which are used for removing harmful cations. Zeolite composites
      with LDHs can absorb ammonium and phosphate ions in rivers and lakes, whereas
      zeolite/apatite composites can immobilize the radioactive iodine. These
      geomaterials are essential for environmental remediation.

PMID- 27877457
TI  - Hierarchical structures of ZnO spherical particles synthesized solvothermally.
AB  - We review the solvothermal synthesis, using a mixture of ethylene glycol (EG) and
      water as the solvent, of zinc oxide (ZnO) particles having spherical and flower
      like shapes and hierarchical nanostructures. The preparation conditions of the
      ZnO particles and the microscopic characterization of the morphology are
      summarized. We found the following three effects of the ratio of EG to water on
      the formation of hierarchical structures: (i) EG restricts the growth of ZnO
      microcrystals, (ii) EG promotes the self-assembly of small crystallites into
      spheroidal particles and (iii) the high water content of EG results in hollow
      spheres.

PMID- 27877456
TI  - Antifouling properties of hydrogels.
AB  - Marine sessile organisms easily adhere to submerged solids such as rocks, metals
      and plastics, but not to seaweeds and fishes, which are covered with soft and wet
      'hydrogel'. Inspired by this fact, we have studied long-term antifouling
      properties of hydrogels against marine sessile organisms. Hydrogels, especially
      those containing hydroxy group and sulfonic group, show excellent antifouling
      activity against barnacles both in laboratory assays and in the marine
      environment. The extreme low settlement on hydrogels in vitro and in vivo is
      mainly caused by antifouling properties against the barnacle cypris.

PMID- 27877459
TI  - Material design and structural color inspired by biomimetic approach.
AB  - Generation of structural color is one of the essential functions realized by
      living organisms, and its industrial reproduction can result in numerous
      applications. From this viewpoint, the mechanisms, materials, analytical methods
      and fabrication technologies of the structural color are reviewed in this paper.
      In particular, the basic principles of natural photonic materials, the ideas
      developed from these principles, the directions of applications and practical
      industrial realizations are presented by summarizing the recent research results.

PMID- 27877458
TI  - X-ray diffraction as a promising tool to characterize bone nanocomposites.
AB  - To understand the characteristics of bone at the tissue level, the structure,
      organization and mechanical properties of the underlying levels down to the
      nanoscale as well as their mutual interactions need to be investigated. Such
      information would help understand changes in the bone properties including
      stiffness, strength and toughness and provide ways to assess the aged and
      diseased bones and the development of next generation of bio-inspired materials.
      X-ray diffraction techniques have gained increased interest in recent years as
      useful non-destructive tools for investigating the nanostructure of bone. This
      review provides an overview on the recent progress in this field and briefly
      introduces the related experimental approach. The application of x-ray
      diffraction to elucidating the structural and mechanical properties of mineral
      crystals in bone is reviewed in terms of characterization of in situ strain,
      residual stress-strain and crystal orientation.

PMID- 27877461
TI  - Novel redox nanomedicine improves gene expression of polyion complex vector.
AB  - Gene therapy has generated worldwide attention as a new medical technology. While
      non-viral gene vectors are promising candidates as gene carriers, they have
      several issues such as toxicity and low transfection efficiency. We have
      hypothesized that the generation of reactive oxygen species (ROS) affects gene
      expression in polyplex supported gene delivery systems. The effect of ROS on the
      gene expression of polyplex was evaluated using a nitroxide radical-containing
      nanoparticle (RNP) as an ROS scavenger. When polyethyleneimine (PEI)/pGL3 or PEI
      alone was added to the HeLa cells, ROS levels increased significantly. In
      contrast, when (PEI)/pGL3 or PEI was added with RNP, the ROS levels were
      suppressed. The luciferase expression was increased by the treatment with RNP in
      a dose-dependent manner and the cellular uptake of pDNA was also increased.
      Inflammatory cytokines play an important role in ROS generation in vivo. In
      particular, tumor necrosis factor (TNF)-alpha caused intracellular ROS generation
      in HeLa cells and decreased gene expression. RNP treatment suppressed ROS
      production even in the presence of TNF-alpha and increased gene expression. This
      anti-inflammatory property of RNP suggests that it may be used as an effective
      adjuvant for non-viral gene delivery systems.

PMID- 27877460
TI  - The toughening mechanism of nacre and structural materials inspired by nacre.
AB  - The structure and the toughening mechanism of nacre have been the subject of
      intensive research over the last 30 years. This interest originates from nacre's
      excellent combination of strength, stiffness and toughness, despite its high, for
      a biological material, volume fraction of inorganic phase, typically 95%. Owing
      to the improvement of nanoscale measurement and observation techniques,
      significant progress has been made during the last decade in understanding the
      mechanical properties of nacre. The structure, microscopic deformation behavior
      and toughening mechanism on the order of nanometers have been investigated, and
      the importance of hierarchical structure in nacre has been recognized. This
      research has led to the fabrication of multilayer composites and films inspired
      by nacre with a layer thickness below 1 MUm. Some of these materials reproduce
      the inorganic/organic interaction and hierarchical structure beyond mere
      morphology mimicking. In the first part of this review, we focus on the
      hierarchical architecture, macroscopic and microscopic deformation and fracture
      behavior, as well as toughening mechanisms in nacre. Then we summarize recent
      progress in the fabrication of materials inspired by nacre taking into
      consideration its mechanical properties.

PMID- 27877462
TI  - Improvement in device performance from a mixture of a liquid crystal and
      photosensitive acrylic prepolymer with the photoinduced vertical alignment
      method.
AB  - In a multicomponent nematic liquid crystal (NLC) mixture of a liquid crystal
      (negative-type NLC) and a photosensitive acrylic prepolymer, photopolymerization
      upon UV irradiation induces the separation of the LC and photosensitive acrylic
      prepolymer layers, thereby leading to a vertical arrangement of LC molecules. In
      this study, we propose a simple vertical alignment method for LC molecules, by
      adding a chiral smectic A (SmA*) liquid crystal having homeotropic texture
      characteristics to an NLC mixture solution. Measurements of electro-optical
      properties revealed that the addition of the SmA* LC not only strengthened the
      anchoring force of the copolymer alignment film surface, but also significantly
      enhanced the contrast ratio (~73%), response time and grayscale switching
      performance of the device.

PMID- 27877463
TI  - BMP-2-loaded silica nanotube fibrous meshes for bone generation.
AB  - Silica nanotube fibrous meshes were fabricated as multiple functional matrices
      for both delivering bone morphological protein-2 (BMP-2) and supporting
      osteoblast attachment and proliferation. The meshes were fabricated via a
      collagen-templated sol-gel route and consisted of tubular silica with open ends.
      BMP-2 was loaded to the meshes by soaking in BMP-2 solution. The meshes
      effectively enabled the attachment and proliferation of osteoblast MC3T3-E1 cells
      and delivered bioactive BMP-2 to stimulate cell differentiation. These results
      demonstrate the potential use of the meshes in bone generation applications.

PMID- 27877465
TI  - Negative thermal expansion materials: technological key for control of thermal
      expansion.
AB  - Most materials expand upon heating. However, although rare, some materials
      contract upon heating. Such negative thermal expansion (NTE) materials have
      enormous industrial merit because they can control the thermal expansion of
      materials. Recent progress in materials research enables us to obtain materials
      exhibiting negative coefficients of linear thermal expansion over -30 ppm K-1.
      Such giant NTE is opening a new phase of control of thermal expansion in
      composites. Specifically examining practical aspects, this review briefly
      summarizes materials and mechanisms of NTE as well as composites containing NTE
      materials, based mainly on activities of the last decade.

PMID- 27877464
TI  - Gate bias-dependent junction characteristics of silicon nanowires suspended
      between polysilicon electrodes.
AB  - Realistic integration of 1D materials into future nanodevices is limited by the
      lack of a manipulation process that allows a large number of nanowires to be
      arranged into an integrated circuit. In this work, we have grown Si nanowire
      bridges using a thin-film catalyst in a batch process at 200  degrees C and
      characterized the produced devices consisting of a p+-Si contact electrode, a
      suspended Si nanochannel, and a polysilicon contact electrode. Both the
      electrodes and connecting lines are made of Si-based materials by conventional
      low-pressure chemical vapor deposition. The results indicate that these devices
      can act as gate-controllable Schottky diodes in integrated nanocircuits.

PMID- 27877466
TI  - Sidewall GaAs tunnel junctions fabricated using molecular layer epitaxy.
AB  - In this article we review the fundamental properties and applications of sidewall
      GaAs tunnel junctions. Heavily impurity-doped GaAs epitaxial layers were prepared
      using molecular layer epitaxy (MLE), in which intermittent injections of
      precursors in ultrahigh vacuum were applied, and sidewall tunnel junctions were
      fabricated using a combination of device mesa wet etching of the GaAs MLE layer
      and low-temperature area-selective regrowth. The fabricated tunnel junctions on
      the GaAs sidewall with normal mesa orientation showed a record peak current
      density of 35 000 A cm-2. They can potentially be used as terahertz devices such
      as a tunnel injection transit time effect diode or an ideal static induction
      transistor.

PMID- 27877467
TI  - Recent progress in mesoporous titania materials: adjusting morphology for
      innovative applications.
AB  - This review article summarizes recent developments in mesoporous titania
      materials, particularly in the fields of morphology control and applications. We
      first briefly introduce the history of mesoporous titania materials and then
      review several synthesis approaches. Currently, mesoporous titania nanoparticles
      (MTNs) have attracted much attention in various fields, such as medicine,
      catalysis, separation and optics. Compared with bulk mesoporous titania
      materials, which are above a micrometer in size, nanometer-sized MTNs have
      additional properties, such as fast mass transport, strong adhesion to substrates
      and good dispersion in solution. However, it has generally been known that the
      successful synthesis of MTNs is very difficult owing to the rapid hydrolysis of
      titanium-containing precursors and the crystallization of titania upon thermal
      treatment. Finally, we review four emerging fields including photocatalysis,
      photovoltaic devices, sensing and biomedical applications of mesoporous titania
      materials. Because of its high surface area, controlled porous structure,
      suitable morphology and semiconducting behavior, mesoporous titania is expected
      to be used in innovative applications.

PMID- 27877468
TI  - Soft x-ray reflectometry, hard x-ray photoelectron spectroscopy and transmission
      electron microscopy investigations of the internal structure of TiO2(Ti)/SiO2/Si
      stacks.
AB  - We developed a mathematical analysis method of reflectometry data and used it to
      characterize the internal structure of TiO2/SiO2/Si and Ti/SiO2/Si stacks. Atomic
      concentration profiles of all the chemical elements composing the samples were
      reconstructed from the analysis of the reflectivity curves measured versus the
      incidence angle at different soft x-ray reflection (SXR) photon energies. The
      results were confirmed by the conventional techniques of hard x-ray photoelectron
      spectroscopy (HXPES) and high-resolution transmission electron microscopy
      (HRTEM). The depth variation of the chemical composition, thicknesses and
      densities of individual layers extracted from SXR and HXPES measurements are in
      close agreement and correlate well with the HRTEM images.

PMID- 27877469
TI  - Synthesis, characterization and antibacterial activity of superparamagnetic
      nanoparticles modified with glycol chitosan.
AB  - Iron oxide nanoparticles (IONPs) were synthesized by coprecipitation of iron
      salts in alkali media followed by coating with glycol chitosan (GC-coated IONPs).
      Both bare and GC-coated IONPs were subsequently characterized and evaluated for
      their antibacterial activity. Comparison of Fourier transform infrared spectra
      and thermogravimetric data of bare and GC-coated IONPs confirmed the presence of
      GC coating on IONPs. Magnetization curves showed that both bare and GC-coated
      IONPs are superparamagnetic and have saturation magnetizations of 70.3 and 59.8
      emu g-1, respectively. The IONP size was measured as ~8-9 nm by transmission
      electron microscopy, and their crystal structure was assigned to magnetite from x
      ray diffraction patterns. Both bare and GC-coated IONPs inhibited the growths of
      Escherichia coli ATCC 8739 and Salmonella enteritidis SE 01 bacteria better than
      the antibiotics linezolid and cefaclor, as evaluated by the agar dilution assay.
      GC-coated IONPs showed higher potency against E. coli O157:H7 and Staphylococcus
      aureus ATCC 10832 than bare IONPs. Given their biocompatibility and antibacterial
      properties, GC-coated IONPs are a potential nanomaterial for in vivo
      applications.

PMID- 27877470
TI  - Transient charge-masking effect of applied voltage on electrospinning of pure
      chitosan nanofibers from aqueous solutions.
AB  - The processing of a polyelectrolyte (whose functionality is derived from its
      ionized functional groups) into a nanofiber may improve its functionality and
      yield multiple functionalities. However, the electrospinning of nanofibers from
      polyelectrolytes is imperfect because polyelectrolytes differ considerably from
      neutral polymers in their rheological properties. In our study, we attempt to
      solve this problem by applying a voltage of opposite polarity to charges on a
      polyelectrolyte. The application of this 'countervoltage' can temporarily mask or
      screen a specific rheological property of the polyelectrolyte, making it behave
      as a neutral polymer. This approach can significantly contribute to the
      development of new functional nanofiber materials.

PMID- 27877472
TI  - Can the use of pulsed direct current induce oscillation in the applied pressure
      during spark plasma sintering?
AB  - The spark plasma sintering (SPS) process is known for its rapid densification of
      metals and ceramics. The mechanism behind this rapid densification has been
      discussed during the last few decades and is yet uncertain. During our SPS
      experiments we noticed oscillations in the applied pressure, related to a change
      in electric current. In this study, we investigated the effect of pulsed
      electrical current on the applied mechanical pressure and related changes in
      temperature. We eliminated the effect of sample shrinkage in the SPS setup and
      used a transparent quartz die allowing direct observation of the sample. We found
      that the use of pulsed direct electric current in our apparatus induces pressure
      oscillations with the amplitude depending on the current density. While sintering
      Ti samples we observed temperature oscillations resulting from pressure
      oscillations, which we attribute to magnetic forces generated within the SPS
      apparatus. The described current-pressure-temperature relations might increase
      understanding of the SPS process.

PMID- 27877471
TI  - On the origin of fine structure in the photoluminescence spectra of the beta
      sialon:Eu2+ green phosphor.
AB  - The photoluminescence (PL) and PL excitation (PLE) spectra of Si6-z Al z O z N8-z
      (beta-sialon):Eu2+ phosphors with small z values (z=0.025-0.24) were studied at
      room temperature and 6 K. The PL and PLE spectra exhibit fine structure with the
      PL lines being as sharp as 45-55 nm even at room temperature; this fine structure
      was enhanced by decreasing the z value. These results can be used for expanding
      the color gamut of liquid crystal displays, particularly in the blue-green
      region. From low-temperature measurements, the fine PLE structure was ascribed to
      discrete energy levels of 7FJ states. The 4f65d excited states of Eu2+ are
      considered to be localized near the 4f orbital. This is because the bonding of
      Eu2+ with surrounding atoms is ionic rather than covalent. Lattice phonon
      absorptions were also observed in the PLE spectrum, revealing that the optically
      active Eu2+ ions are located in the beta-sialon crystal. The PL spectrum of the
      sample with the smallest z value (0.025) consists of a sharp zero-phonon line and
      lattice phonon replicas, which results in a sharp and asymmetric spectral shape.

PMID- 27877473
TI  - Feasibility study of polyurethane shape-memory polymer actuators for pressure
      bandage application.
AB  - The feasibility of laboratory-synthesized polyurethane-based shape-memory polymer
      (SMPU) actuators has been investigated for possible application in medical
      pressure bandages where gradient pressure is required between the ankle and the
      knee for treatment of leg ulcers. In this study, using heat as the stimulant,
      SMPU strip actuators have been subjected to gradual and cyclic stresses; their
      recovery force, reproducibility and reusability have been monitored with respect
      to changes in temperature and circumference of a model leg, and the stress
      relaxation at various temperatures has been investigated. The findings suggest
      that SMPU actuators can be used for the development of the next generation of
      pressure bandages.

PMID- 27877474
TI  - Lithium aluminosilicate reinforced with carbon nanofiber and alumina for
      controlled-thermal-expansion materials.
AB  - Materials with a very low or tailored thermal expansion have many applications
      ranging from cookware to the aerospace industry. Among others, lithium
      aluminosilicates (LAS) are the most studied family with low and negative thermal
      expansion coefficients. However, LAS materials are electrical insulators and have
      poor mechanical properties. Nanocomposites using LAS as a matrix are promising in
      many applications where special properties are achieved by the addition of one or
      two more phases. The main scope of this work is to study the sinterability of
      carbon nanofiber (CNFs)/LAS and CNFs/alumina/LAS nanocomposites, and to adjust
      the ratio among components for obtaining a near-zero or tailored thermal
      expansion. Spark plasma sintering of nanocomposites, consisting of commercial
      CNFs and alumina powders and an ad hoc synthesized beta-eucryptite phase, is
      proposed as a solution to improving mechanical and electrical properties compared
      with the LAS ceramics obtained under the same conditions. X-ray diffraction
      results on phase compositions and microstructure are discussed together with
      dilatometry data obtained in a wide temperature range (-150 to 450  degrees C).
      The use of a ceramic LAS phase makes it possible to design a nanocomposite with a
      very low or tailored thermal expansion coefficient and exceptional electrical and
      mechanical properties.

PMID- 27877475
TI  - Functionalized diatom silica microparticles for removal of mercury ions.
AB  - Diatom silica microparticles were chemically modified with self-assembled
      monolayers of 3-mercaptopropyl-trimethoxysilane (MPTMS), 3-aminopropyl
      trimethoxysilane (APTES) and n-(2-aminoethyl)-3-aminopropyl-trimethoxysilane
      (AEAPTMS), and their application for the adsorption of mercury ions (Hg(II)) is
      demonstrated. Fourier transform infrared spectroscopy and x-ray photoelectron
      spectroscopy analyses revealed that the functional groups (-SH or -NH2) were
      successfully grafted onto the diatom silica surface. The kinetics and efficiency
      of Hg(II) adsorption were markedly improved by the chemical functionalization of
      diatom microparticles. The relationship among the type of functional groups, pH
      and adsorption efficiency of mercury ions was established. The Hg(II) adsorption
      reached equilibrium within 60 min with maximum adsorption capacities of 185.2,
      131.7 and 169.5 mg g-1 for particles functionalized with MPTMS, APTES and
      AEAPTMS, respectively. The adsorption behavior followed a pseudo-second-order
      reaction model and Langmuirian isotherm. These results show that mercapto- or
      amino-functionalized diatom microparticles are promising natural, cost-effective
      and environmentally benign adsorbents suitable for the removal of mercury ions
      from aqueous solutions.

PMID- 27877477
TI  - Progress in thermomechanical control of steel plates and their commercialization.
AB  - The water-cooled thermomechanical control process (TMCP) is a technology for
      improving the strength and toughness of water-cooled steel plates, while allowing
      control of the microstructure, phase transformation and rolling. This review
      describes metallurgical aspects of the microalloying of steel, such as niobium
      addition, and discusses advantages of TMCP, for example, in terms of weldability,
      which is reduced upon alloying. Other covered topics include the development of
      equipment, distortions in steel plates, peripheral technologies such as steel
      making and casting, and theoretical modeling, as well as the history of property
      control in steel plate production and some early TMCP technologies. We provide
      some of the latest examples of applications of TMCP steel in various industries
      such as shipbuilding, offshore structures, building construction, bridges,
      pipelines, penstocks and cryogenic tanks. This review also introduces high heat
      affected-zone toughness technologies, wherein the microstructure of steel is
      improved by the addition of fine particles of magnesium-containing sulfides and
      magnesium- or calcium-containing oxides. We demonstrate that thanks to ongoing
      developments TMCP has the potential to meet the ever-increasing demands of steel
      plates.

PMID- 27877476
TI  - Quantitative comparison between poly(L-arginine) and poly(L-lysine) at each step
      of polyplex-based gene transfection using a microinjection technique.
AB  - Among the well-studied polypeptide-type gene carriers, transfection efficiency is
      empirically known to be higher for poly(L-arginine) (PR) than poly(L-lysine)
      (PK). The big difference between PR and PK should be determined at one of the
      intracellular trafficking steps based on the different charge densities,
      structures or PKa values. However, the endosomal escape and the intranuclear
      transcription efficiency in living cells have not been clarified yet. In this
      study, a novel method for quantifying the intranuclear transcription efficiency
      and the nuclear transport of the polyplex is established based on the nuclear and
      the cytosolic microinjection technique, and the results for PK and PR with
      different molecular weights (MWs) are compared in living cells. The intranuclear
      transcription efficiency is the same in PR and PK and it decreases rapidly with
      increasing MW, in spite of the commonly measured transfection efficiency. The
      transcription efficiency is strongly suppressed at high MW and strongly
      correlates with the polyplex forming ability expressed as a critical ratio of the
      number of polypeptide cationic groups to the number of pDNA anionic groups. When
      considered with the results of the cellular uptake and in vitro transfection with
      or without chloroquine, the rate-limiting step for their gene transfer is the
      buffering effect-independent endosomal escape.

PMID- 27877478
TI  - Surface science studies of metal hexaborides.
AB  - Over 30 years of surface science research on metal hexaborides are reviewed. Of
      this class of compounds, lanthanum hexaboride has been the subject of the
      majority of the studies because of its outstanding properties as a thermionic
      emitter. The use of LaB6 cathodes as an electron source stems from the unusually
      low work function of ~2.5 eV for the (100) surface combined with a low
      evaporation rate at high temperatures. Of particular interest has been the
      determination of the surface geometric and electronic structure responsible for
      the low work function and how the work function is affected by various
      adsorbates. The low-index faces of single crystals of LaB6 and other hexaborides
      have been studied with a variety of ultrahigh vacuum surface science methods to
      gain a better understanding of the structure and properties of the clean surfaces
      as well as their interactions with gases such as O2, H2O and CO.

PMID- 27877479
TI  - Photoinduced superhydrophilicity of TiO2 thin film with hierarchical Cu doping.
AB  - Hydrophilic Cu-TiO2 thin films with a gradient in the Cu concentration were
      prepared on glass by layer-by-layer dip-coating from TiO2 precursors. The effects
      of the Cu doping on the structure and properties of TiO2 self-cleaning thin films
      are discussed. The Cu gradient markedly affects the hydrophilicity of the films,
      with the water contact angle significantly reduced compared with those of the
      pure or uniformly doped TiO2 thin films. This enhanced hydrophilicity is
      explained by the more efficient absorption of the solar light and by the reduced
      recombination of photoexcited electrons and holes in the TiO2 films containing a
      gradient of Cu dopants.

PMID- 27877480
TI  - Patterning titania with the conventional and modified micromolding in capillaries
      technique from sol-gel and dispersion solutions.
AB  - We report TiO2 patterns obtained by a soft-lithographic technique called
      'micromolding in capillaries' using sol-gel and dispersion solutions. A
      comparison between patterning with a sol-gel and dispersion solutions has been
      performed. The patterns obtained from sol-gel solutions showed good adhesion to
      the substrate and uniform shapes, but large shrinkage, whereas those obtained
      from dispersion solution had high solid content, but exhibited poor adhesion and
      non-uniform shapes. A fabrication method of a layer-by-layer structured pattern
      is also demonstrated. This type of pattern may find application in sensors,
      waveguides and other photonics elements. The occurrence of an undesirable residue
      layer, which hinders the fabrication of isolated patterns, is highlighted and a
      method of prevention is suggested.

PMID- 27877481
TI  - Simple and cost-effective fabrication of size-tunable zinc oxide architectures by
      multiple size reduction technique.
AB  - We present a simple size reduction technique for fabricating 400 nm zinc oxide
      (ZnO) architectures using a silicon master containing only microscale
      architectures. In this approach, the overall fabrication, from the master to the
      molds and the final ZnO architectures, features cost-effective UV
      photolithography, instead of electron beam lithography or deep-UV
      photolithography. A photosensitive Zn-containing sol-gel precursor was used to
      imprint architectures by direct UV-assisted nanoimprint lithography (UV-NIL). The
      resulting Zn-containing architectures were then converted to ZnO architectures
      with reduced feature sizes by thermal annealing at 400  degrees C for 1 h. The
      imprinted and annealed ZnO architectures were also used as new masters for the
      size reduction technique. ZnO pillars of 400 nm diameter were obtained from a
      silicon master with pillars of 1000 nm diameter by simply repeating the size
      reduction technique. The photosensitivity and contrast of the Zn-containing
      precursor were measured as 6.5 J cm-2 and 16.5, respectively. Interesting complex
      ZnO patterns, with both microscale pillars and nanoscale holes, were demonstrated
      by the combination of dose-controlled UV exposure and a two-step UV-NIL.

PMID- 27877482
TI  - Turning refuse plastic into multi-walled carbon nanotube forest.
AB  - A novel and effective method was devised for synthesizing a vertically aligned
      carbon nanotube (CNT) forest on a substrate using waste plastic obtained from
      commercially available water bottles. The advantages of the proposed method are
      the speed of processing and the use of waste as a raw material. A mechanism for
      the CNT growth was also proposed. The growth rate of the CNT forest was ~2.5 MUm
      min-1. Transmission electron microscopy images indicated that the outer diameters
      of the CNTs were 20-30 nm on average. The intensity ratio of the G and D Raman
      bands was 1.27 for the vertically aligned CNT forest. The Raman spectrum showed
      that the wall graphitization of the CNTs, synthesized via the proposed method was
      slightly higher than that of commercially available multi-walled carbon nanotubes
      (MWCNTs). We expect that the proposed method can be easily adapted to the
      disposal of other refuse materials and applied to MWCNT production industries.

PMID- 27877484
TI  - Weighing a single atom using a coupled plasmon-carbon nanotube system.
AB  - We propose an optical weighing technique with a sensitivity down to a single
      atom, using a surface plasmon and a doubly clamped carbon nanotube resonator. The
      mass of a single atom is determined via the vibrational frequency shift of the
      carbon nanotube while the atom attaches to the nanotube surface. Owing to the
      ultralight mass and high quality factor of the carbon nanotube, and the spectral
      enhancement by the use of surface plasmon, this method results in a narrow
      linewidth (kHz) and high sensitivity (2.3*10-28 Hz. g-1), which is five orders of
      magnitude more sensitive than traditional electrical mass detection techniques.

PMID- 27877483
TI  - Paclitaxel-loaded poly(lactide-co-glycolide)/poly(ethylene vinyl acetate)
      composite for stent coating by ultrasonic atomizing spray.
AB  - The mixture of poly(lactide-co-glycolide) (PLGA) and poly(ethylene vinyl acetate)
      (PEVA) forms a homogeneous liquid in an organic solvent such as tetrahydrofuran,
      and a phase-separated PLGA/PEVA composite can be prepared from it by evaporating
      the organic solvent. Exploiting this phenomenon, we designed a novel method of
      preparing a drug-loaded PLGA/PEVA composite and used it for coating drug-eluting
      stents (DESs). Paclitaxel (PTX), an anticancer drug, was chosen as a model drug.
      PLGA acts as a microdepot for PTX, and PEVA provides mechanical strength to the
      coating material. The presence of PLGA in the PLGA/PEVA composite suppressed PTX
      crystallization in the coating material, and PTX showed a sustained release rate
      over more than 30 days. The mechanical strength of the PLGA/PEVA composite was
      better than that of PEVA used as a control. After coating the stent with a
      PLGA/PEVA composite using ultrasonic atomizing spray, the morphology of the
      coated material was observed by scanning electron microscopy, and the release
      pattern of PTX was measured by high-performance liquid chromatography.

PMID- 27877486
TI  - Rheological and micro-Raman time-series characterization of enzyme sol-gel
      solution toward morphological control of electrospun fibers.
AB  - Rheological and micro-Raman time-series characterizations were used to
      investigate the chemical evolutionary changes of silica sol-gel mixtures for
      electrospinning fibers to immobilize an enzyme (tyrosinase). Results of dynamic
      rheological measurements agreed with the expected structural transitions
      associated with reacting sol-gel systems. The electrospinning sols exhibited
      shear-thinning behavior typical of a power law model. Ultrafine (200-300 nm
      diameter) fibers were produced at early and late times within the reaction window
      of approximately one hour from initial mixing of sol solutions with and without
      enzyme; diameter distributions of these fibers showed much smaller deviations
      than expected. The enzyme markedly increased magnitudes of both elastic and
      viscous moduli but had no significant impact on final fiber diameters, suggesting
      that the shear-thinning behavior of both sol-gel mixtures is dominant in the
      fiber elongation process. The time course and scale for the electrospinning batch
      fabrication show strong correlations between the magnitudes in rheological
      property changes over time and the chemical functional group evolution obtained
      from micro-Raman time-series analysis of the reacting sol-gel systems.

PMID- 27877485
TI  - Versatile sputtering technology for Al2O3 gate insulators on graphene.
AB  - We report a novel, sputtering-based fabrication method of Al2O3 gate insulators
      on graphene. Electrical performance of dual-gated mono- and bilayer exfoliated
      graphene devices is presented. Sputtered Al2O3 layers possess comparable quality
      to oxides obtained by atomic layer deposition with respect to a high relative
      dielectric constant of about 8, as well as low-hysteresis performance and high
      breakdown voltage. We observe a moderate carrier mobility of about 1000 cm2 V-1 s
      1 in monolayer graphene and 350 cm2 V-1 s-1 in bilayer graphene, respectively.
      The mobility decrease can be attributed to the resonant scattering on atomic
      scale defects, likely originating from the Al precursor layer evaporated prior to
      sputtering.

PMID- 27877487
TI  - Hydrogen generation from water using Mg nanopowder produced by arc plasma method.
AB  - We report that hydrogen gas can be easily produced from water at room temperature
      using a Mg nanopowder (30-1000 nm particles, average diameter 265 nm). The Mg
      nanopowder was produced by dc arc melting of a Mg ingot in a chamber with mixed
      gas atmosphere (20% N2-80% Ar) at 0.1 MPa using custom-built nanopowder
      production equipment. The Mg nanopowder was passivated with a gas mixture of 1%
      O2 in Ar for 12 h in the final step of the synthesis, after which the nanopowder
      could be safely handled in ambient air. The nanopowder vigorously reacted with
      water at room temperature, producing 110 ml of hydrogen gas per 1 g of powder in
      600 s. This amount corresponds to 11% of the hydrogen that could be generated by
      the stoichiometric reaction between Mg and water. Mg(OH)2 flakes formed on the
      surface of the Mg particles as a result of this reaction. They easily peeled off,
      and the generation of hydrogen continued until all the Mg was consumed.

PMID- 27877489
TI  - One-step route to a hybrid TiO2/Ti x W1-x N nanocomposite by in situ selective
      carbothermal nitridation.
AB  - Metal oxide/nitride nanocomposites have many existing and potential applications,
      e.g. in energy conversion or ammonia synthesis. Here, a hybrid oxide/nitride
      nanocomposite (anatase/Ti x W1-x N) was synthesized by an ammonia-free sol-gel
      route. Synchrotron x-ray diffraction, complemented with electron microscopy and
      thermogravimetric analysis, was used to study the structure, composition and
      mechanism of formation of the nanocomposite. The nanocomposite contained
      nanoparticles (<5 nm diameter) of two highly intermixed phases. This was found to
      arise from controlled nucleation and growth of a single oxide intermediate from
      the gel precursor, followed by phase separation and in situ selective
      carbothermal nitridation. Depending on the preparation conditions, the
      composition varied from anatase/Ti x W1-x N at low W content to an isostructural
      mixture of Ti-rich and W-rich Ti x W1-x N at high W content. In situ selective
      carbothermal nitridation offers a facile route to the synthesis of nitride-oxide
      nanocomposites. This conceptually new approach is a significant advance from
      previous methods, which generally require ammonolysis of a pre-synthesized oxide.

PMID- 27877488
TI  - Programmed self-assembly of large pi-conjugated molecules into electroactive one
      dimensional nanostructures.
AB  - Electroactive one-dimensional (1D) nano-objects possess inherent unidirectional
      charge and energy transport capabilities along with anisotropic absorption and
      emission of light, which are of great advantage for the development of nanometer
      scale electronics and optoelectronics. In particular, molecular nanowires formed
      by self-assembly of pi-conjugated molecules attract increasing attention for
      application in supramolecular electronics. This review introduces recent topics
      related to electroactive molecular nanowires. The nanowires are classified into
      four categories with respect to the electronic states of the constituent
      molecules: electron donors, acceptors, donor-acceptor pairs and miscellaneous
      molecules that display interesting electronic properties. Although many
      challenges still remain for practical use, state-of-the-art 1D supramolecular
      nanomaterials have already brought significant advances to both fundamental
      chemical sciences and technological applications.

PMID- 27877490
TI  - The effect of cross-linking on the microstructure, mechanical properties and
      biocompatibility of electrospun polycaprolactone-gelatin/PLGA-gelatin/PLGA
      chitosan hybrid composite.
AB  - In this study, multilayered scaffolds composed of polycaprolactone (PCL)
      gelatin/poly(lactic-co-glycolic acid) (PLGA)-gelatin/PLGA-chitosan artificial
      blood vessels were fabricated using a double-ejection electrospinning system. The
      mixed fibers from individual materials were observed by scanning electron
      microscopy. The effects of the cross-linking process on the microstructure,
      mechanical properties and biocompatibility of the fibers were examined. The
      tensile stress and liquid strength of the cross-linked artificial blood vessels
      were 2.3 MPa and 340 mmHg, respectively, and were significantly higher than for
      the non-cross-linked vessel (2.0 MPa and 120 mmHg). The biocompatibility of the
      cross-linked artificial blood vessel scaffold was examined using the MTT assay
      and by evaluating cell attachment and cell proliferation. The cross-linked PCL
      gelatin/PLGA-gelatin/PLGA-chitosan artificial blood vessel scaffold displayed
      excellent flexibility, was able to withstand high pressures and promoted cell
      growth; thus, this novel material holds great promise for eventual use in
      artificial blood vessels.

PMID- 27877491
TI  - Low-cost and fast synthesis of nanoporous silica cryogels for thermal insulation
      applications.
AB  - Nanoporous silica cryogels with a high specific surface area of 1095 m2 g-1 were
      fabricated using tert-butyl alcohol as a reaction solvent, via a cost-effective
      sol-gel process followed by vacuum freeze drying. The total time of cryogel
      production was reduced markedly to one day. The molar ratio of solvent/precursor,
      which was varied from 5 to 13, significantly affected the porous structure and
      thermal insulating properties of the cryogels. The silica cryogels with low
      densities in the range of 0.08-0.18 g cm-3 and thermal conductivities as low as
      6.7 mW (m.K)-1 at 100 Pa and 28.3 mW (m.K)-1 at 105 Pa were obtained using this
      new technique.

PMID- 27877492
TI  - Direct stamping of silver nanoparticles toward residue-free thick electrode.
AB  - Direct stamping of functional materials has been developed for cost-effective and
      process-effective manufacturing of nano/micro patterns. However, there remain
      several challenging issues like the perfect removal of the residual layer and
      realization of high aspect ratio. We have demonstrated facile fabrication of
      flexible strain sensors that have microscale thick interdigitated capacitors with
      no residual layer by a simple direct stamping with silver nanoparticles (AgNPs).
      Polyurethane (PU) prepolymer was utilized as an adhesive layer to transfer AgNPs
      more efficiently during the separation step of the flexible stamp from directly
      stamped AgNPs. Scanning electron microscopy images and energy dispersive x-ray
      spectroscopy analysis revealed residue-free transfer of microscale thick
      interdigitated electrodes onto two different flexible substrates (elastomeric and
      brittle) for the application to highly sensitive strain sensors.

PMID- 27877493
TI  - Shape effect of ultrafine-grained structure on static fracture toughness in low
      alloy steel.
AB  - A 0.4C-2Si-1Cr-1Mo steel with an ultrafine elongated grain (UFEG) structure and
      an ultrafine equiaxed grain (UFG) structure was fabricated by multipass caliber
      rolling at 773 K and subsequent annealing at 973 K. A static three-point bending
      test was conducted at ambient temperature and at 77 K. The strength-toughness
      balance of the developed steels was markedly better than that of conventionally
      quenched and tempered steel with a martensitic structure. In particular, the
      static fracture toughness of the UFEG steel, having a yield strength of 1.86 GPa
      at ambient temperature, was improved by more than 40 times compared with
      conventional steel having a yield strength of 1.51 GPa. Furthermore, even at 77
      K, the fracture toughness of the UFEG steel was about eight times higher than
      that of the conventional and UFG steels, despite the high strength of the UFEG
      steel (2.26 GPa). The UFG steel exhibited brittle fracture behavior at 77 K, as
      did the conventional steel, and no dimple structure was observed on the fracture
      surface. Therefore, it is difficult to improve the low-temperature toughness of
      the UFG steel by grain refinement only. The shape of crystal grains plays an
      important role in delamination toughening, as do their refinement and
      orientation.

PMID- 27877494
TI  - Design and preparation of stress-free epitaxial BaTiO3 polydomain films by RF
      magnetron sputtering.
AB  - Domain structures of BaTiO3 thick films grown on (100) SrTiO3 single-crystal
      substrates were engineered using an RF magnetron sputtering deposition process.
      By tuning the sputtering power and cooling rate and using an off-axis sputtering
      technique to prepare conducting perovskite oxide bottom electrode with
      heteroepitaxial quality, we have deposited epitaxial tetragonal single-domain and
      polydomain BaTiO3 films with a self-assembled three-domain architecture. The
      electrical properties and microstructure of the BaTiO3 films were characterized,
      and a c/a1/a2 cellular polydomain structure was clearly observed in as-grown
      films by optical microscopy. Such a polydomain structure was a consequence of a
      complete relaxation of misfit stresses of the film. Engineering of this self
      assembled microstructure has great potential in providing large, field-tunable
      pyroelectric and electromechanical responses in next-generation microelectronic
      devices and micro-electro-mechanical systems (MEMS).

PMID- 27877495
TI  - Effective lattice stabilization of gadolinium aluminate garnet (GdAG) via Lu3+
      doping and development of highly efficient (Gd,Lu)AG:Eu3+ red phosphors.
AB  - The metastable garnet lattice of Gd3Al5O12 is stabilized by doping with smaller
      Lu3+, which then allows an effective incorporation of larger Eu3+ activators. The
      [(Gd1-x Lu x )1-y Eu y ]3Al5O12 (x = 0.1-0.5, y = 0.01-0.09) garnet solid
      solutions, calcined from their precursors synthesized via carbonate
      coprecipitation, exhibit strong luminescence at 591 nm (the 5D0 -> 7F1 magnetic
      dipole transition of Eu3+) upon UV excitation into the charge transfer band (CTB)
      at ~239 nm, with CIE chromaticity coordinates of x = 0.620 and y = 0.380 (orange
      red). The quenching concentration of Eu3+ was estimated at ~5 at.% (y = 0.05),
      and the quenching was attributed to exchange interactions. Partial replacement of
      Gd3+ with Lu3+ up to 50 at.% (x = 0.5) while keeping Eu3+ at the optimal content
      of 5 at.% does not significantly alter the peak positions of the CTB and 5D0 ->
      7F1 emission bands but slightly weakens both bands owing to the higher
      electronegativity of Lu3+. The effects of processing temperature (1000-1500 
      degrees C) and Lu/Eu contents on the intensity, quantum efficiency, lifetime and
      asymmetry factor of luminescence were thoroughly investigated. The
      [(Gd0.7Lu0.3)0.95Eu0.05]3Al5O12 phosphor processed at 1500  degrees C exhibits a
      high internal quantum efficiency of ~83.2% under 239 nm excitation, which, in
      combination with the high theoretical density, favors its use as a new type of
      photoluminescent and scintillation material.

PMID- 27877496
TI  - Electrospinning of aligned fibers with adjustable orientation using auxiliary
      electrodes.
AB  - A conventional electrospinning setup was upgraded by two turnable plate-like
      auxiliary high-voltage electrodes that allowed aligned fiber deposition in
      adjustable directions. Fiber morphology was analyzed by scanning electron
      microscopy and attenuated total reflection Fourier transform infrared
      spectroscopy (FTIR-ATR). The auxiliary electric field constrained the jet bending
      instability and the fiber deposition became controllable. At target speeds of 0.9
      m s-1 90% of the fibers had aligned within 2 degrees , whereas the angular spread
      was 70 degrees  without the use of auxiliary electrodes. It was even possible to
      orient fibers perpendicular to the rotational direction of the target. The fiber
      diameter became smaller and its distribution narrower, while according to the
      FTIR-ATR measurement the molecular orientation of the polymer was unaltered. This
      study comprehensively documents the feasibility of directed fiber deposition and
      offers an easy upgrade to existing electrospinning setups.

PMID- 27877497
TI  - Microwave sintering and in vitro study of defect-free stable porous multilayered
      HAp-ZrO2 artificial bone scaffold.
AB  - Continuously porous hydroxyapatite (HAp)/t-ZrO2 composites containing concentric
      laminated frames and microchanneled bodies were fabricated by an extrusion
      process. To investigate the mechanical properties of HAp/t-ZrO2 composites, the
      porous composites were sintered at different temperatures using a microwave
      furnace. The microstructure was designed to imitate that of natural bone,
      particularly small bone, with both cortical and spongy bone sections. Each
      microchannel was separated by alternating lamina of HAp, HAp-(t-ZrO2) and t-ZrO2.
      HAp and ZrO2 phases existed on the surface of the microchannel and the core zone
      to increase the biocompatibility and mechanical properties of the HAp-ZrO2
      artificial bone. The sintering behavior was evaluated and the optimum sintering
      temperature was found to be 1400  degrees C, which produced a stable scaffold.
      The material characteristics, such as the microstructure, crystal structure and
      compressive strength, were evaluated in detail for different sintering
      temperatures. A detailed in vitro study was carried out using MTT assay, western
      blot analysis, gene expression by polymerase chain reaction and laser confocal
      image analysis of cell proliferation. The results confirmed that HAp-ZrO2
      performs as an artificial bone, showing excellent cell growth, attachment and
      proliferation behavior using osteoblast-like MG63 cells.

PMID- 27877498
TI  - Production and properties of electrosprayed sericin nanopowder.
AB  - Sericin is a proteinous substrate that envelops fibroin (silk) fiber, and its
      recovery provides significant economical and social benefits. Sericin is an
      antibacterial agent that resists oxidation and absorbs moisture and UV light. In
      powder form, sericin has a wide range of applications in food, cosmetics and drug
      delivery. Asides from other techniques of producing powder, such as precipitation
      and spray drying, electrospraying can yield solid nanoparticles, particularly in
      the submicron range. Here, we report the production of sericin nanopowder by
      electrospraying. Sericin sponge was recovered from Bombyx mori cocoons through a
      high-temperature, high-pressure process, followed by centrifugation and freeze
      drying of the sericin solution. The electrospraying solution was prepared by
      dissolving the sericin sponge in dimethyl sulfoxide. We demonstrate that
      electrospraying is capable of producing sericin nanopowder with an average
      particle size of 25 nm, which is by far smaller than the particles produced by
      other techniques. The electrosprayed sericin nanopowder consists of small
      crystallites and exhibits a high moisture absorbance.

PMID- 27877499
TI  - Hierarchical adaptive nanostructured PVD coatings for extreme tribological
      applications: the quest for nonequilibrium states and emergent behavior.
AB  - Adaptive wear-resistant coatings produced by physical vapor deposition (PVD) are
      a relatively new generation of coatings which are attracting attention in the
      development of nanostructured materials for extreme tribological applications. An
      excellent example of such extreme operating conditions is high performance
      machining of hard-to-cut materials. The adaptive characteristics of such coatings
      develop fully during interaction with the severe environment. Modern adaptive
      coatings could be regarded as hierarchical surface-engineered nanostructural
      materials. They exhibit dynamic hierarchy on two major structural scales: (a)
      nanoscale surface layers of protective tribofilms generated during friction and
      (b) an underlying nano/microscaled layer. The tribofilms are responsible for some
      critical nanoscale effects that strongly impact the wear resistance of adaptive
      coatings. A new direction in nanomaterial research is discussed: compositional
      and microstructural optimization of the dynamically regenerating nanoscaled
      tribofilms on the surface of the adaptive coatings during friction. In this
      review we demonstrate the correlation between the microstructure, physical,
      chemical and micromechanical properties of hard coatings in their dynamic
      interaction (adaptation) with environment and the involvement of complex natural
      processes associated with self-organization during friction. Major physical,
      chemical and mechanical characteristics of the adaptive coating, which play a
      significant role in its operating properties, such as enhanced mass transfer, and
      the ability of the layer to provide dissipation and accumulation of frictional
      energy during operation are presented as well. Strategies for adaptive
      nanostructural coating design that enhance beneficial natural processes are
      outlined. The coatings exhibit emergent behavior during operation when their
      improved features work as a whole. In this way, as higher-ordered systems, they
      achieve multifunctionality and high wear resistance under extreme tribological
      conditions.

PMID- 27877501
TI  - Hydrothermal synthesis and properties of NiFe2O4@BaTiO3 composites with well
      matched interface.
AB  - NiFe2O4@BaTiO3 multiferroic composite particles were produced by a simple
      hydrothermal method in two steps: preparing NiFe2O4 nanoparticles and then
      synthesizing core-shell nanocomposites. Multiferroic composite ceramics were
      sintered from these powders. X-ray diffraction, Raman scattering and energy
      dispersive x-ray analyses indicated that the core-shell composites with a NiFe2O4
      core and BaTiO3 shell were formed in the hydrothermal environment. Different
      types of sharp interfaces were self-assembled owing to the minimization of direct
      elastic energy. The saturation magnetization of the composites linearly increased
      with the NiFe2O4 content while the dielectric constant decreased. A dielectric
      peak appeared at around 460  degrees C because of the oxygen vacancies in the
      BaTiO3 ceramics. It resulted in an enhancement of magnetic permeability in the
      composites, indicating magnetoelectric coupling that was also observed by direct
      magnetoelectric measurements.

PMID- 27877502
TI  - Effects of vertically aligned carbon nanotubes on shear performance of laminated
      nanocomposite bonded joints.
AB  - The main objective is to improve the most commonly addressed weakness of the
      laminated composites (i.e. delamination due to poor interlaminar strength) using
      carbon nanotubes (CNTs) as reinforcement between the laminae and in the
      transverse direction. In this work, a chemical vapor deposition technique has
      been used to grow dense vertically aligned arrays of CNTs over the surface of
      chemically treated two-dimensionally woven cloth and fiber tows. The nanoforest
      like fabrics can be used to fabricate three-dimensionally reinforced laminated
      nanocomposites. The presence of CNTs aligned normal to the layers and in-between
      the layers of laminated composites is expected to considerably enhance the
      properties of the laminates. To demonstrate the effectiveness of our approach,
      composite single lap-joint specimens were fabricated for interlaminar shear
      strength testing. It was observed that the single lap-joints with through-the
      thickness CNT reinforcement can carry considerably higher shear stresses and
      strains. Close examination of the test specimens showed that the failure of
      samples with CNT nanoforests was completely cohesive, while the samples without
      CNT reinforcement failed adhesively. This concludes that the adhesion of adjacent
      carbon fabric layers can be considerably improved owing to the presence of
      vertically aligned arrays of CNT nanoforests.

PMID- 27877504
TI  - Hydrogen plasma treatment of very thin p-type nanocrystalline Si films grown by
      RF-PECVD in the presence of B(CH3)3.
AB  - We have characterized the structure and electrical properties of p-type
      nanocrystalline silicon films prepared by radio-frequency plasma-enhanced
      chemical vapor deposition and explored optimization methods of such layers for
      potential applications in thin-film solar cells. Particular attention was paid to
      the characterization of very thin (~20 nm) films. The cross-sectional morphology
      of the layers was studied by fitting the ellipsometry spectra using a multilayer
      model. The results suggest that the crystallization process in a high-pressure
      growth regime is mostly realized through a subsurface mechanism in the absence of
      the incubation layer at the substrate-film interface. Hydrogen plasma treatment
      of a 22-nm-thick film improved its electrical properties (conductivity increased
      more than ten times) owing to hydrogen insertion and Si structure rearrangements
      throughout the entire thickness of the film.

PMID- 27877505
TI  - Development of a simple method for fabrication of transparent conductive films
      with high mechanical strength.
AB  - We have developed a simple method of fabricating transparent conductive films
      with a high mechanical strength on glass and indium tin oxide substrates. It does
      not require a large excess of organic solvents and polymerization catalysts and
      can yield smooth films by spin-coating of a mixture of a commercially available
      aqueous dispersion of poly(3,4-ethylenedioxythiophene)-poly(4-styrene sulfonate)
      and a neat liquid of tetraethyl orthosilicate. Preparation conditions such as
      feed ratio, kinds of additives, and annealing temperature and time were optimized
      to give highly conductive, transparent and mechanically strong films.

PMID- 27877500
TI  - Progress of key strategies in development of electrospun scaffolds: bone tissue.
AB  - There has been unprecedented development in tissue engineering (TE) over the last
      few years owing to its potential applications, particularly in bone
      reconstruction or regeneration. In this article, we illustrate several advantages
      and disadvantages of different approaches to the design of electrospun TE
      scaffolds. We also review the major benefits of electrospun fibers for three
      dimensional scaffolds in hard connective TE applications and identify the key
      strategies that can improve the mechanical properties of scaffolds for bone TE
      applications. A few interesting results of recent investigations have been
      explained for future trends in TE scaffold research.

PMID- 27877503
TI  - 3D polylactide-based scaffolds for studying human hepatocarcinoma processes in
      vitro.
AB  - We evaluated the combination of leaching techniques and melt blending of polymers
      and particles for the preparation of highly interconnected three-dimensional
      polymeric porous scaffolds for in vitro studies of human hepatocarcinoma
      processes. More specifically, sodium chloride and poly(ethylene glycol) (PEG)
      were used as water-soluble porogens to form porous and solvent-free poly(L,D
      lactide) (PLA)-based scaffolds. Several characterization techniques, including
      porosimetry, image analysis and thermogravimetry, were combined to improve the
      reliability of measurements and mapping of the size, distribution and
      microarchitecture of pores. We also investigated the effect of processing, in PLA
      based blends, on the simultaneous bulk/surface modifications and pore
      architectures in the scaffolds, and assessed the effects on human hepatocarcinoma
      viability and cell adhesion. The influence of PEG molecular weight on the
      scaffold morphology and cell viability and adhesion were also investigated.
      Morphological studies indicated that it was possible to obtain scaffolds with
      well-interconnected pores of assorted sizes. The analysis confirmed that SK-Hep1
      cells adhered well to the polymeric support and emitted surface protrusions
      necessary to grow and differentiate three-dimensional systems. PEGs with higher
      molecular weight showed the best results in terms of cell adhesion and viability.

PMID- 27877506
TI  - Phase relationships in the quasi-ternary LaO1.5-SiO2-MgO system at 1773 K.
AB  - Phase relationships in the LaO1.5-SiO2-MgO quasi-ternary system at 1773 K were
      investigated by powder x-ray diffraction (XRD) analysis applying single- and
      multiple-phase Rietveld methods. Most of the formed phases satisfied the Gibbs'
      phase rule, except for the samples containing LaO1.5 and a liquid phase at 1773
      K. The detection of segregated MgO phases was difficult in the XRD profiles of
      the compositional samples around the oxyapatite single phase because the MgO
      peaks were weak and heavily overlapped by peaks from the oxyapatite and La(OH)3
      phases. The solid solubility limit of MgO in oxyapatite was determined not only
      from the chemical composition of the oxyapatite phase, which was confirmed by
      XRD, but also from several phase boundary compositions among the two-phase and
      three-phase regions based on the Gibbs' phase rule. Formation of a liquid phase
      at 1773 K was observed in a wide range of compositions and considered when
      constructing the phase diagram.

PMID- 27877507
TI  - High-strength zirconium diboride-based ceramic composites consolidated by low
      temperature hot pressing.
AB  - Two compositions of ZrB2-based ceramic composites containing Si3N4, Al2O3 and
      Y2O3 have been hot-pressed at different temperatures between 1673 and 1773 K for
      60 min in vacuum. The densification behavior of the composites was examined
      during the sintering process. The microstructures of the composites were
      characterized by scanning electron microscopy, and the crystalline phases were
      identified by x-ray diffraction. The effects of Al2O3 and Y2O3 additives on the
      densification behavior and flexural strength were assessed. A relative density of
      ~95% was obtained after sintering at 1723 K or higher temperatures. The
      microstructures of the composites consisted of (Zr,Y)B2, alpha-Si3N4 and
      Y3(Al,Si)5O12 phases. The room-temperature flexural strength increased with the
      amount of additives and approached 1 GPa.

PMID- 27877508
TI  - Synthesis of biocompatible multicolor luminescent carbon dots for bioimaging
      applications.
AB  - Water-soluble carbon dots (C-dots) were prepared through microwave-assisted
      pyrolysis of an aqueous solution of dextrin in the presence of sulfuric acid. The
      C-dots produced showed multicolor luminescence in the entire visible range,
      without adding any surface-passivating agent. X-ray diffraction and Fourier
      transform infrared spectroscopy studies revealed the graphitic nature of the
      carbon and the presence of hydrophilic groups on the surface, respectively. The
      formation of uniformly distributed C-dots and their luminescent properties were,
      respectively, revealed from transmission electron microscopy and confocal laser
      scanning microscopy. The biocompatible nature of C-dots was confirmed by a
      cytotoxicity assay on MDA-MB-468 cells and their cellular uptake was assessed
      through a localization study.

PMID- 27877510
TI  - Focus on superconducting properties of iron chalcogenides.

PMID- 27877509
TI  - Chemical stabilization of porous silicon for enhanced biofunctionalization with
      immunoglobulin.
AB  - Porous silicon (PSi) is widely used in biological experiments, owing to its
      biocompatibility and well-established fabrication methods that allow tailoring
      its surface. Nevertheless, there are some unresolved issues such as deciding
      whether the stabilization of PSi is necessary for its biological applications and
      evaluating the effects of PSi stabilization on the surface biofunctionalization
      with proteins. In this work we demonstrate that non-stabilized PSi is prone to
      detachment owing to the stress induced upon biomolecular adsorption.
      Biofunctionalized non-stabilized PSi loses the interference properties
      characteristic of a thin film, and groove-like structures resulting from a final
      layer collapse were observed by scanning electron microscopy. Likewise, direct
      PSi derivatization with 3-aminopropyl-triethoxysilane (APTS) does not stabilize
      PSi against immunoglobulin biofunctionalization. To overcome this problem, we
      developed a simple chemical process of stabilizing PSi (CoxPSi) for biological
      applications, which has several advantages over thermal stabilization (ToxPSi).
      The process consists of chemical oxidation in H2O2, surface derivatization with
      APTS and a curing step at 120  degrees C. This process offers integral
      homogeneous PSi morphology, hydrophilic surface termination (contact angle theta
      = 26 degrees ) and highly efficient derivatized and biofunctionalized PSi
      surfaces (six times more efficient than ToxPSi). All these features are highly
      desirable for biological applications, such as biosensing, where our results can
      be used for the design and optimization of the biomolecular immobilization
      cascade on PSi surfaces.

PMID- 27877512
TI  - Photonic metamaterials: a new class of materials for manipulating light waves.
AB  - A decade of research on metamaterials (MMs) has yielded great progress in
      artificial electromagnetic materials in a wide frequency range from microwave to
      optical frequencies. This review outlines the achievements in photonic MMs that
      can efficiently manipulate light waves from near-ultraviolet to near-infrared in
      subwavelength dimensions. One of the key concepts of MMs is effective refractive
      index, realizing values that have not been obtained in ordinary solid materials.
      In addition to the high and low refractive indices, negative refractive indices
      have been reported in some photonic MMs. In anisotropic photonic MMs of high
      contrast refractive indices, the polarization and phase of plane light waves were
      efficiently transformed in a well-designed manner, enabling remarkable
      miniaturization of linear optical devices such as polarizers, wave plates and
      circular dichroic devices. Another feature of photonic MMs is the possibility of
      unusual light propagation, paving the way for a new subfield of transfer optics.
      MM lenses having super-resolution and cloaking effects were introduced by
      exploiting novel light-propagating modes. Here, we present a new approach to
      describing photonic MMs definitely by resolving the electromagnetic eigenmodes.
      Two representative photonic MMs are addressed: the so-called fishnet MM slabs,
      which are known to have effective negative refractive index, and a three
      dimensional MM based on a multilayer of a metal and an insulator. In these
      photonic MMs, we elucidate the underlying eigenmodes that induce unusual light
      propagations. Based on the progress of photonic MMs, the future potential and
      direction are discussed.

PMID- 27877513
TI  - Revisiting some chalcogenides for thermoelectricity.
AB  - Thermoelectric materials that are efficient well above ambient temperature are
      needed to convert waste-heat into electricity. Many thermoelectric oxides were
      investigated for this purpose, but their power factor (PF) values were too small
      (~10-4 W m-1 K-2) to yield a satisfactory figure of merit zT. Changing the anions
      from O2- to S2- and then to Se2- is a way to increase the covalency. In this
      review, some examples of sulfides (binary Cr-S or derived from layered TiS2) and
      an example of selenides, AgCrSe2, have been selected to illustrate the
      characteristic features of their physical properties. The comparison of the only
      two semiconducting binary chromium sulfides and of a layered AgCrSe2 selenide
      shows that the PF values are also in the same order of magnitude as those of
      transition metal oxides. In contrast, the PF values of the layered sulfides TiS2
      and Cu0.1TiS2 are higher, reaching ~10-3 W m-1 K-2. Apparently the magnetism
      related to the Cr-S network is detrimental for the PF when compared to the d0
      character of the Ti4+ based sulfides. Finally, the very low PF in AgCrSe2 (PF =
      2.25 * 10-4 W m1 K-2 at 700 K) is compensated by a very low thermal conductivity
      (kappa = 0.2 W m-1 K-1 from the measured Cp) leading to the highest zT value
      among the reviewed compounds (zT700K = 0.8). The existence of a glassy-like state
      for the Ag+ cations above 475 K is believed to be responsible for this result.
      This result demonstrates that the phonon engineering in open frameworks is a very
      interesting way to generate efficient thermoelectric materials.

PMID- 27877511
TI  - Paradigm shift from self-assembly to commanded assembly of functional materials:
      recent examples in porphyrin/fullerene supramolecular systems.
AB  - Current nanotechnology based on top-down nanofabrication may encounter a variety
      of drawbacks in the near future so that development of alternative methods,
      including the so-called bottom-up approach, has attracted considerable attention.
      However, the bottom-up strategy, which often relies on spontaneous self-assembly,
      might be inefficient in the development of the requisite functional materials and
      systems. Therefore, assembly processes controlled by external stimuli might be a
      plausible strategy for the development of bottom-up nanotechnology. In this
      review, we demonstrate a paradigm shift from self-assembly to commanded assembly
      by describing several examples of assemblies of typical functional molecules,
      i.e. porphyrins and fullerenes. In the first section, we describe recent progress
      in the design and study of self-assembled and co-assembled supramolecular
      architectures of porphyrins and fullerenes. Then, we show examples of assembly
      induced by external stimuli. We emphasize the paradigm shift from self-assembly
      to commanded assembly by describing the recently developed electrochemical
      coupling layer-by-layer (ECC-LbL) methodology.

PMID- 27877514
TI  - Superconducting properties of iron chalcogenide thin films.
AB  - Iron chalcogenides, binary FeSe, FeTe and ternary FeTe x Se1-x , FeTe x S1-x and
      FeTe:O x , are the simplest compounds amongst the recently discovered iron-based
      superconductors. Thin films of iron chalcogenides present many attractive
      features that are covered in this review, such as: (i) easy fabrication and
      epitaxial growth on common single-crystal substrates; (ii) strong enhancement of
      superconducting transition temperature with respect to the bulk parent compounds
      (in FeTe0.5Se0.5, zero-resistance transition temperature Tc0bulk = 13.5 K, but
      Tc0film = 19 K on LaAlO3 substrate); (iii) high critical current density (Jc ~
      0.5 *106 A cm2 at 4.2 K and 0 T for FeTe0.5Se0.5 film deposited on CaF2, and
      similar values on flexible metallic substrates (Hastelloy tapes buffered by ion
      beam assisted deposition) with a weak dependence on magnetic field; (iv) high
      upper critical field (~50 T for FeTe0.5Se0.5, Bc2(0), with a low anisotropy,
      gamma ~ 2). These highlights explain why thin films of iron chalcogenides have
      been widely studied in recent years and are considered as promising materials for
      applications requiring high magnetic fields (20-50 T) and low temperatures (2-10
      K).

PMID- 27877516
TI  - Physics and chemistry of layered chalcogenide superconductors.
AB  - Structural and physical properties of layered chalcogenide superconductors are
      summarized. In particular, we review the remarkable properties of the Fe
      chalcogenide superconductors, FeSe and FeTe-based materials. Furthermore, we
      introduce the recently discovered BiS2-based layered superconductors and discuss
      their prospects.

PMID- 27877515
TI  - Magnetic excitations in iron chalcogenide superconductors.
AB  - Nuclear magnetic resonance and neutron scattering experiments in iron
      chalcogenide superconductors are reviewed to make a survey of the magnetic
      excitations in FeSe, FeSe1-x Te x and alkali-metal-doped Ax Fe2-y Se2 (A = K, Rb,
      Cs, etc). In FeSe, the intimate relationship between the spin fluctuations and
      superconductivity can be seen universally for the variations in the off
      stoichiometry, the Co-substitution and applied pressure. The isovalent compound
      FeTe has a magnetic ordering with different wave vector from that of other Fe
      based magnetic materials. The transition temperature Tc of FeSe increases with Te
      substitution in FeSe1-x Te x with small x, and decreases in the vicinity of the
      end member FeTe. The spin fluctuations are drastically modified by the Te
      substitution. In the vicinity of the end member FeTe, the low-energy part of the
      spin fluctuation is dominated by the wave vector of the ordered phase of FeTe;
      however, the reduction of Tc shows that it does not support superconductivity.
      The presence of same wave vector as that of other Fe-based superconductors in
      FeSe1-x Te x and the observation of the resonance mode demonstrate that FeSe1-x
      Te x belongs to the same group as most of other Fe-based superconductors in the
      entire range of x, where superconductivity is mediated by the spin fluctuations
      whose wave vector is the same as the nesting vector between the hole pockets and
      the electron pockets. On the other hand, the spin fluctuations differ for alkali
      metal-doped Ax Fe2-y Se2 and FeSe or other Fe-based superconductors in their wave
      vector and strength in the low-energy part, most likely because of the different
      Fermi surfaces. The resonance mode with different wave vector suggests that Ax
      Fe2-y Se2 has an exceptional superconducting symmetry among Fe-based
      superconductors.

PMID- 27877518
TI  - Iron chalcogenide superconductors at high magnetic fields.
AB  - Iron chalcogenide superconductors have become one of the most investigated
      superconducting materials in recent years due to high upper critical fields,
      competing interactions and complex electronic and magnetic phase diagrams. The
      structural complexity, defects and atomic site occupancies significantly affect
      the normal and superconducting states in these compounds. In this work we review
      the vortex behavior, critical current density and high magnetic field pair
      breaking mechanism in iron chalcogenide superconductors. We also point to
      relevant structural features and normal-state properties.

PMID- 27877517
TI  - Superconductivity and magnetism in 11-structure iron chalcogenides in relation to
      the iron pnictides.
AB  - This is a review of the magnetism and superconductivity in '11'-type Fe
      chalcogenides, as compared to the Fe-pnictide materials. The chalcogenides show
      many differences from the pnictides, as might be anticipated from their very
      varied chemistries. These differences include stronger renormalizations that
      might imply stronger correlation effects as well as different magnetic ordering
      patterns. Nevertheless the superconducting state and mechanism for
      superconductivity are apparently similar for the two classes of materials.
      Unanswered questions and challenges to theory are emphasized.

PMID- 27877520
TI  - Theoretical and experimental investigation of magnetotransport in iron
      chalcogenides.
AB  - We explore the electronic, transport and thermoelectric properties of Fe1+y Se x
      Te1-x compounds to clarify the mechanisms of superconductivity in Fe-based
      compounds. We carry out first-principles density functional theory (DFT)
      calculations of structural, electronic, magnetic and transport properties and
      measure resistivity, Hall resistance and Seebeck effect curves. All the transport
      properties exhibit signatures of the structural/magnetic transitions, such as
      discontinuities and sign changes of the Seebeck coefficient and of the Hall
      resistance. These features are reproduced by calculations provided that
      antiferromagnetic correlations are taken into account and experimental values of
      lattice constants are considered in DFT calculations. On the other hand, the
      temperature dependences of the transport properties can not be fully reproduced,
      and to improve the agreement between experiment and DFT calculations it is
      necessary to go beyond the constant relaxation time approximation and take into
      account correlation effects.

PMID- 27877519
TI  - High-pressure studies on Tc and crystal structure of iron chalcogenide
      superconductors.
AB  - The superconducting transition temperature, Tc, in iron-based solids can be
      enhanced by applied pressure: Tc increases from 8 to 37 K for the 11-type FeSe
      when the pressure is raised from 0 to 4 GPa. High-pressure studies can elucidate
      the mechanism of superconductivity in such novel materials. In this paper, we
      present a high-pressure study of Fe(Se1-x Te x ) and Fe(Se1-x S x ). In the case
      of Fe(Se1-x Te x ), the maximum Tc under high pressure did not exceed the Tc of
      FeSe, which can be attributed to the structural transition to the monoclinic
      phase. For Fe(Se1-x S x ) (0 < x < 0.3), Tc exhibited a significant increase with
      pressure; however, the maximum Tc under high pressure did not exceed the Tc of
      FeSe. This may be due to the disorder induced by substituting S for Se, which is
      similar to the pressure effect on Tc for the 1111-type superconductor Ca(Fe1-x Co
      x )AsF. The Tc of Fe(Se1-x S x ) showed a complex behavior below 1 GPa, first
      decreasing and then increasing with increasing pressure. From high-pressure x-ray
      diffraction measurements, the Tc (P) curve was correlated with the local
      structural parameter.

PMID- 27877521
TI  - Te concentration dependent photoemission and inverse-photoemission study of FeSe1
      xTex.
AB  - We have characterized the electronic structure of FeSe1-x Te x for various x
      values using soft x-ray photoemission spectroscopy (SXPES), high-resolution
      photoemission spectroscopy (HRPES) and inverse photoemission spectroscopy (IPES).
      The SXPES valence band spectral shape shows that the 2 eV feature in FeSe, which
      was ascribed to the lower Hubbard band in previous theoretical studies, becomes
      less prominent with increasing x. HRPES exhibits systematic x dependence of the
      structure near the Fermi level (EF): its splitting near EF and filling of the
      pseudogap in FeSe. IPES shows two features, near EF and approximately 6 eV above
      EF; the former may be related to the Fe 3d states hybridized with chalcogenide p
      states, while the latter may consist of plane-wave-like and Se d components. In
      the incident electron energy dependence of IPES, the density of states near EF
      for FeSe and FeTe has the Fano lineshape characteristic of resonant behavior.
      These compounds exhibit different resonance profiles, which may reflect the
      differences in their electronic structures. By combining the PES and IPES data
      the on-site Coulomb energy was estimated at 3.5 eV for FeSe.

PMID- 27877523
TI  - Electrical isolation of dislocations in Ge layers on Si(001) substrates through
      CMOS-compatible suspended structures.
AB  - Suspended crystalline Ge semiconductor structures are created on a Si(001)
      substrate by a combination of epitaxial growth and simple patterning from the
      front surface using anisotropic underetching. Geometric definition of the surface
      Ge layer gives access to a range of crystalline planes that have different etch
      resistance. The structures are aligned to avoid etch-resistive planes in making
      the suspended regions and to take advantage of these planes to retain the
      underlying Si to support the structures. The technique is demonstrated by forming
      suspended microwires, spiderwebs and van der Pauw cross structures. We finally
      report on the low-temperature electrical isolation of the undoped Ge layers. This
      novel isolation method increases the Ge resistivity to 280 Omega cm at 10 K, over
      two orders of magnitude above that of a bulk Ge on Si(001) layer, by removing
      material containing the underlying misfit dislocation network that otherwise
      provides the main source of electrical conduction.

PMID- 27877524
TI  - From biomedical-engineering research to clinical application and
      industrialization.

PMID- 27877522
TI  - Photoassisted fabrication of zinc indium oxide/oxysulfide composite for enhanced
      photocatalytic H2 evolution under visible-light irradiation.
AB  - A photoassisted approach has been developed to synthesize a zinc indium oxide
      (Zn5In2O8)/oxysulfide composite through in situ sulfuration of vacancy-rich
      Zn5In2O8. It was found that vacancies have a considerable impact on the formation
      of the composite. The composite exhibited an increased photocatalytic H2
      evolution activity under visible-light irradiation, which probably resulted from
      the enhanced ability to separate photoinduced electrons and holes. The H2
      evolution rate over the composite was about 17 times higher when using vacancy
      rich rather than conventional Zn5In2O8. This study provides a new method of
      improving the activity of photocatalysts.

PMID- 27877526
TI  - Research and development of metals for medical devices based on clinical needs.
AB  - The current research and development of metallic materials used for medicine and
      dentistry is reviewed. First, the general properties required of metals used in
      medical devices are summarized, followed by the needs for the development of
      alpha + beta type Ti alloys with large elongation and beta type Ti alloys with a
      low Young's modulus. In addition, nickel-free Ni-Ti alloys and austenitic
      stainless steels are described. As new topics, we review metals that are
      bioabsorbable and compatible with magnetic resonance imaging. Surface treatment
      and modification techniques to improve biofunctions and biocompatibility are
      categorized, and the related problems are presented at the end of this review.
      The metal surface may be biofunctionalized by various techniques, such as dry and
      wet processes. These techniques make it possible to apply metals to scaffolds in
      tissue engineering.

PMID- 27877525
TI  - Cell membrane-inspired phospholipid polymers for developing medical devices with
      excellent biointerfaces.
AB  - This review article describes fundamental aspects of cell membrane-inspired
      phospholipid polymers and their usefulness in the development of medical devices.
      Since the early 1990s, polymers composed of 2-methacryloyloxyethyl
      phosphorylcholine (MPC) units have been considered in the preparation of
      biomaterials. MPC polymers can provide an artificial cell membrane structure at
      the surface and serve as excellent biointerfaces between artificial and
      biological systems. They have also been applied in the surface modification of
      some medical devices including long-term implantable artificial organs. An MPC
      polymer biointerface can suppress unfavorable biological reactions such as
      protein adsorption and cell adhesion - in other words, specific biomolecules
      immobilized on an MPC polymer surface retain their original functions. MPC
      polymers are also being increasingly used for creating biointerfaces with
      artificial cell membrane structures.

PMID- 27877528
TI  - Processing of nanolitre liquid plugs for microfluidic cell-based assays.
AB  - Plugs, i.e. droplets formed in a microchannel, may revolutionize microfluidic
      cell-based assays. This study describes a microdevice that handles nanolitre
      scale liquid plugs for the preparation of various culture setups and subsequent
      cellular assays. An important feature of this mode of liquid operation is that
      the recirculation flow generated inside the plug promotes the rapid mixing of
      different solutions after plugs are merged, and it keeps cell suspensions
      homogeneous. Thus, serial dilutions of reagents and cell suspensions with
      different cell densities and cell types were rapidly performed using nanolitres
      of solution. Cells seeded through the plug processing grew well in the
      microdevice, and subsequent plug processing was used to detect the glucose
      consumption of cells and cellular responses to anticancer agents. The plug-based
      microdevice may provide a useful platform for cell-based assay systems in various
      fields, including fundamental cell biology and drug screening applications.

PMID- 27877529
TI  - A smart hydrogel-based time bomb triggers drug release mediated by pH-jump
      reaction.
AB  - We demonstrate a timed explosive drug release from smart pH-responsive hydrogels
      by utilizing a phototriggered spatial pH-jump reaction. A photoinitiated proton
      releasing reaction of o-nitrobenzaldehyde (o-NBA) was integrated into poly(N
      isopropylacrylamide-co-2-carboxyisopropylacrylamide) (P(NIPAAm-co-CIPAAm))
      hydrogels. o-NBA-hydrogels demonstrated the rapid release of protons upon UV
      irradiation, allowing the pH inside the gel to decrease to below the pKa value of
      P(NIPAAm-co-CIPAAm). The generated protons diffused gradually toward the non
      illuminated area, and the diffusion kinetics could be controlled by adjusting the
      UV irradiation time and intensity. After irradiation, we observed the enhanced
      release of entrapped L-3,4-dihydroxyphenylalanine (DOPA) from the gels, which was
      driven by the dissociation of DOPA from CIPAAm. Local UV irradiation also
      triggered the release of DOPA from the non-illuminated area in the gel via the
      diffusion of protons. Conventional systems can activate only the illuminated
      region, and their response is discontinuous when the light is turned off. The
      ability of the proposed pH-jump system to permit gradual activation via proton
      diffusion may be beneficial for the design of predictive and programmable devices
      for drug delivery.

PMID- 27877530
TI  - Temperature-responsive electrospun nanofibers for 'on-off' switchable release of
      dextran.
AB  - We propose a new type of 'smart' nanofiber (NF) with dynamically and reversibly
      tunable properties for the 'on-off' controlled release of the polysaccharide
      dextran. The fibers are produced by electrospinning copolymers of N
      isopropylacrylamide (NIPAAm) and N-hydroxymethylacrylamide (HMAAm). The OH groups
      of HMAAm are subsequently crosslinked by thermal curing. The copolymers were
      successfully fabricated into a well-defined nanofibrous structure with a diameter
      of about 600-700 nm, and the fibers preserved their morphology even after thermal
      curing. The resulting crosslinked NFs showed rapid and reversible volume changes
      in aqueous media in response to cycles of temperature alternation. The fibrous
      morphology was maintained for the crosslinked NFs even after the cycles of
      temperature alternation, while non-crosslinked NFs collapsed and dispersed
      quickly in the aqueous solution. Dextran-containing NFs were prepared by
      electrospinning the copolymers blended with fluorescein isothiocyanate (FITC)
      dextran, and the 'on-off' switchable release of FITC-dextran from the crosslinked
      NFs was observed. Almost all the FITC-dextran was released from the NFs after six
      heating cycles, whereas only a negligible amount of FITC-dextran was evolved
      during the cooling process. The reported incorporation of smart properties into
      NFs takes advantage of their extremely large surface area and porosity and is
      expected to provide a simple platform for on-off drug delivery.

PMID- 27877527
TI  - Hydroxylapatite nanoparticles: fabrication methods and medical applications.
AB  - Hydroxylapatite (or hydroxyapatite, HAp) exhibits excellent biocompatibility with
      various kinds of cells and tissues, making it an ideal candidate for tissue
      engineering, orthopedic and dental applications. Nanosized materials offer
      improved performances compared with conventional materials due to their large
      surface-to-volume ratios. This review summarizes existing knowledge and recent
      progress in fabrication methods of nanosized (or nanostructured) HAp particles,
      as well as their recent applications in medical and dental fields. In section 1,
      we provide a brief overview of HAp and nanoparticles. In section 2, fabrication
      methods of HAp nanoparticles are described based on the particle formation
      mechanisms. Recent applications of HAp nanoparticles are summarized in section 3.
      The future perspectives in this active research area are given in section 4.

PMID- 27877531
TI  - Fabrication of DNA-antibody-apatite composite layers for cell-targeted gene
      transfer.
AB  - Surface-mediated gene transfer systems using apatite (Ap)-based composite layers
      have received increased attention in tissue engineering applications owing to
      their safety, biocompatibility and relatively high efficiency. In this study, DNA
      antibody-apatite composite layers (DA-Ap layers), in which DNA and antibody
      molecules are immobilized within a matrix of apatite nanocrystals, were
      fabricated using a biomimetic coating process. They were then assayed for their
      gene transfer capability for application in a specific cell-targeted gene
      transfer. A DA-Ap layer that was fabricated with an anti-CD49f antibody showed a
      higher gene transfer capability to the CD49f-positive CHO-K1 cells than a DNA
      apatite composite layer (D-Ap layer). The antibody facilitated the gene transfer
      capability of the DA-Ap layer only to the specific cells that were expressing
      corresponding antigens. When the DA-Ap layer was fabricated with an anti-N
      cadherin antibody, a higher gene transfer capability compared with the D-Ap layer
      was found in the N-cadherin-positive P19CL6 cells, but not in the N-cadherin
      negative UV?2 cells or in the P19CL6 cells that were pre-blocked with anti-N
      cadherin. Therefore, the antigen-antibody binding that takes place at the cell
      layer interface should be responsible for the higher gene transfer capability of
      the DA-Ap than D-Ap layer. These results suggest that the DA-Ap layer works as a
      mediator in a specific cell-targeted gene transfer system.

PMID- 27877533
TI  - Novel temperature-responsive polymer brushes with carbohydrate residues
      facilitate selective adhesion and collection of hepatocytes.
AB  - Temperature-responsive glycopolymer brushes were designed to investigate the
      effects of grafting architectures of the copolymers on the selective adhesion and
      collection of hypatocytes. Homo, random and block sequences of N
      isopropylacrylamide and 2-lactobionamidoethyl methacrylate were grafted on glass
      substrates via surface-initiated atom transfer radical polymerization. The
      galactose/lactose-specific lectin RCA120 and HepG2 cells were used to test for
      specific recognition of the polymer brushes containing galactose residues over
      the lower critical solution temperatures (LCSTs). RCA120 showed a specific
      binding to the brush surfaces at 37  degrees C. These brush surfaces also
      facilitated the adhesion of HepG2 cells at 37  degrees C under nonserum
      conditions, whereas no adhesion was observed for NIH-3T3 fibroblasts. When the
      temperature was decreased to 25  degrees C, almost all the HepG2 cells detached
      from the block copolymer brush, whereas the random copolymer brush did not
      release the cells. The difference in releasing kinetics of cells from the
      surfaces with different grafting architectures can be explained by the correlated
      effects of significant changes in LCST, mobility, hydrophilicity and mechanical
      properties of the grafted polymer chains. These findings are important for
      designing 'on-off' cell capture/release substrates for various biomedical
      applications such as selective cell separation.

PMID- 27877532
TI  - Mesenchymal stem cell adhesion but not plasticity is affected by high substrate
      stiffness.
AB  - The acknowledged ability of synthetic materials to induce cell-specific responses
      regardless of biological supplies provides tissue engineers with the opportunity
      to find the appropriate materials and conditions to prepare tissue-targeted
      scaffolds. Stem and mature cells have been shown to acquire distinct morphologies
      in vitro and to modify their phenotype when grown on synthetic materials with
      tunable mechanical properties. The stiffness of the substrate used for cell
      culture is likely to provide cells with mechanical cues mimicking given
      physiological or pathological conditions, thus affecting the biological
      properties of cells. The sensitivity of cells to substrate composition and
      mechanical properties resides in multiprotein complexes called focal adhesions,
      whose dynamic modification leads to cytoskeleton remodeling and changes in gene
      expression. In this study, the remodeling of focal adhesions in human mesenchymal
      stem cells in response to substrate stiffness was followed in the first phases of
      cell-matrix interaction, using poly-epsilon-caprolactone planar films with
      similar chemical composition and different elasticity. As compared to mature
      dermal fibroblasts, mesenchymal stem cells showed a specific response to
      substrate stiffness, in terms of adhesion, as a result of differential focal
      adhesion assembly, while their multipotency as a bulk was not significantly
      affected by matrix compliance. Given the sensitivity of stem cells to matrix
      mechanics, the mechanobiology of such cells requires further investigations
      before preparing tissue-specific scaffolds.

PMID- 27877534
TI  - Design of super-elastic biodegradable scaffolds with longitudinally oriented
      microchannels and optimization of the channel size for Schwann cell migration.
AB  - We newly designed super-elastic biodegradable scaffolds with longitudinally
      oriented microchannels for repair and regeneration of peripheral nerve defects.
      Four-armed poly(epsilon-caprolactone-co-D,L-lactide)s (P(CL-co-DLLA)s) were
      synthesized by ring-opening copolymerization of CL and DLLA from terminal
      hydroxyl groups of pentaerythritol, and acryloyl chloride was then reacted with
      the ends of the chains. The end-functionalized P(CL-co-DLLA) was crosslinked in a
      cylindrical mold in the presence of longitudinally oriented silica fibers as the
      templates, which were later dissolved by hydrofluoric acid. The elastic moduli of
      the crosslinked P(CL-co-DLLA)s were controlled between 10-1 and 102 MPa at 37 
      degrees C, depending on the composition. The scaffolds could be elongated to 700%
      of their original size without fracture or damage ('super-elasticity'). Scanning
      electron microscopy images revealed that well-defined and highly aligned multiple
      channels consistent with the mold design were produced in the scaffolds. Owing to
      their elastic nature, the microchannels in the scaffolds did not collapse when
      they were bent to 90 degrees . To evaluate the effect of the channel diameter on
      Schwann cell migration, microchannels were also fabricated in transparent
      poly(dimethylsiloxane), allowing observation of cell migration. The migration
      speed increased with channel size, but the Young's modulus of the scaffold
      decreased as the channel diameter increased. These findings may serve as the
      basis for designing tissue-engineering scaffolds for nerve regeneration and
      investigating the effects of the geometrical and dimensional properties on axonal
      outgrowth.

PMID- 27877535
TI  - Tamibarotene-loaded citric acid-crosslinked alkali-treated collagen matrix as a
      coating material for a drug-eluting stent.
AB  - Tamibarotene-loaded biodegradable matrices with antithrombogenic and drug
      releasing properties were prepared in a crosslinking reaction between amino
      groups of alkali-treated collagen (AlCol) and active ester groups of
      trisuccinimidyl citrate. The resulting matrices were characterized by their
      residual amino group concentrations, swelling ratios and thermal,
      antithrombogenic and drug-releasing properties. It was clarified that the
      addition of tamibarotene does not inhibit matrix formation. After immersion in
      water, the swelling ratio of a matrix became lower than that prior to immersion.
      Thermal analysis indicated that AlCol interacted with tamibarotene. The addition
      of tamibarotene to the matrix did not influence the antithrombogenic property of
      the resulting matrix. A matrix with a high crosslinking density had a prolonged
      tamibarotene elution time. These results demonstrate that tamibarotene-loaded
      matrices have great potential as a coating material for drug-eluting stents.

PMID- 27877536
TI  - Development of an early estimation method for predicting later osteogenic
      differentiation activity of rat mesenchymal stromal cells from their attachment
      areas.
AB  - Cell morphology has received considerable attention in recent years owing to its
      possible relationship with cell functions, including proliferation,
      differentiation, and migration. Recent evidence suggests that extracellular
      environments can also mediate cell functions, particularly cell adhesion. The
      aims of this study were to investigate the correlation between osteogenic
      differentiation activity and the morphology of rat mesenchymal stromal cells
      (MSCs), and to develop a method of estimating osteogenic differentiation
      capability of MSCs on biomaterials. We measured the attachment areas of MSCs on
      substrates with various types of surface after 2 h of seeding, and quantified the
      amount of osteocalcin secreted from MSCs after 3 weeks of culture under
      osteogenic differentiation conditions. MSCs with small attachment areas showed a
      high osteogenic differentiation activity. These findings indicate that cell
      attachment areas correlate well with the osteogenic differentiation activity of
      MSCs. They also suggest that the measurement of cell attachment areas is useful
      for estimating the osteogenic differentiation activity of MSCs and is a practical
      tool for applications of MSCs in regenerative medicine.

PMID- 27877537
TI  - PLLA-collagen and PLLA-gelatin hybrid scaffolds with funnel-like porous structure
      for skin tissue engineering.
AB  - In skin tissue engineering, a three-dimensional porous scaffold is necessary to
      support cell adhesion and proliferation and to guide cells moving into the repair
      area in the wound healing process. Structurally, the porous scaffold should have
      an open and interconnected porous architecture to facilitate homogenous cell
      distribution. Moreover, the scaffolds should be mechanically strong to protect
      deformation during the formation of new skin. In this study, the hybrid scaffolds
      were prepared by forming funnel-like collagen or gelatin sponge on a woven poly(l
      lactic acid) (PLLA) mesh. The hybrid scaffolds combined the advantages of both
      collagen or gelatin (good cell-interactions) and PLLA mesh (high mechanical
      strength). The hybrid scaffolds were used to culture dermal fibroblasts for
      dermal tissue engineering. The funnel-like porous structure promoted homogeneous
      cell distribution and extracellular matrix production. The PLLA mesh reinforced
      the scaffold to avoid deformation. Subcutaneous implantation showed that the PLLA
      collagen and PLLA-gelatin scaffolds promoted the regeneration of dermal tissue
      and epidermis and reduced contraction during the formation of new tissue. These
      results indicate that funnel-like hybrid scaffolds can be used for skin tissue
      regeneration.

PMID- 27877539
TI  - In vitro evaluation of tissue adhesives composed of hydrophobically modified
      gelatins and disuccinimidyl tartrate.
AB  - The effect of the hydrophobic group content in gelatin on the bonding strength of
      novel tissue-penetrating tissue adhesives was evaluated. The hydrophobic groups
      introduced into gelatin were the saturated hexanoyl, palmitoyl, and stearoyl
      groups, and the unsaturated oleoyl group. A collagen casing was employed as an
      adherend to model soft tissue for the in vitro determination of bonding strength
      of tissue adhesives composed of various hydrophobically modified gelatins and
      disuccinimidyl tartrate. The adhesive composed of stearoyl-modified gelatin (7.4%
      stearoyl; 10Ste) and disuccinimidyl tartrate showed the highest bonding strength.
      The bonding strength of the adhesives decreased as the degree of substitution of
      the hydrophobic groups increased. Cell culture experiments demonstrated that
      fluorescein isothiocyanate-labeled 10Ste was integrated onto the surface of
      smooth muscle cells and showed no cytotoxicity. These results suggest that 10Ste
      interacted with the hydrophobic domains of collagen casings, such as hydrophobic
      amino acid residues and cell membranes. Therefore, 10Ste-disuccinimidyl tartrate
      is a promising adhesive for use in aortic dissection.

PMID- 27877538
TI  - Substrate stiffness affects skeletal myoblast differentiation in vitro.
AB  - To maximize the therapeutic efficacy of cardiac muscle constructs produced by
      stem cells and tissue engineering protocols, suitable scaffolds should be
      designed to recapitulate all the characteristics of native muscle and mimic the
      microenvironment encountered by cells in vivo. Moreover, so not to interfere with
      cardiac contractility, the scaffold should be deformable enough to withstand
      muscle contraction. Recently, it was suggested that the mechanical properties of
      scaffolds can interfere with stem/progenitor cell functions, and thus careful
      consideration is required when choosing polymers for targeted applications. In
      this study, cross-linked poly-epsilon-caprolactone membranes having similar
      chemical composition and controlled stiffness in a supra-physiological range were
      challenged with two sources of myoblasts to evaluate the suitability of
      substrates with different stiffness for cell adhesion, proliferation and
      differentiation. Furthermore, muscle-specific and non-related feeder layers were
      prepared on stiff surfaces to reveal the contribution of biological and
      mechanical cues to skeletal muscle progenitor differentiation. We demonstrated
      that substrate stiffness does affect myogenic differentiation, meaning that
      softer substrates can promote differentiation and that a muscle-specific feeder
      layer can improve the degree of maturation in skeletal muscle stem cells.

PMID- 27877540
TI  - Preparation and biological evaluation of hydroxyapatite-coated nickel-free high
      nitrogen stainless steel.
AB  - Calcium phosphate was formed on nickel-free high-nitrogen stainless steel (HNS)
      by chemical solution deposition. The calcium phosphate deposition was enhanced by
      glutamic acid covalently immobilized on the surface of HNS with trisuccinimidyl
      citrate as a linker. X-ray diffraction patterns and Fourier transform infrared
      spectra showed that the material deposited on glutamic acid-immobilized HNS
      within 24 h was low-crystallinity calcium-deficient carbonate-containing
      hydroxyapatite (HAp). The biological activity of the resulting HAp-coated HNS was
      investigated by using a human osteoblast-like MG-63 cell culture. The HAp-coated
      HNS stimulated the alkaline-phosphate activity of the MG-63 culture after 7 days.
      Therefore, HAp-coated HNS is suitable for orthopedic devices and soft tissue
      adhesion materials.

PMID- 27877541
TI  - Surface characterization and cytocompatibility evaluation of silanized magnesium
      alloy AZ91 for biomedical applications.
AB  - Mg alloys with high Al contents have superior corrosion resistance in aqueous
      environments, but poor cytocompatibility compared to that of pure Mg. We have
      silanized the cast AZ91 alloy to improve its cytocompatibility using five
      different silanes: ethyltriethoxysilane (S1), 3-aminopropyltriethoxysilane (S2),
      3-isocyanatopyltriethoxysilane (S3), phenyltriethoxysilane (S4) and
      octadecyltriethoxysilane (S5). The surface hydrophilicity/hydrophobicity was
      evaluated by water contact angle measurements. X-ray photoelectron analysis was
      performed to investigate the changes in surface states and chemical composition.
      All silane reagents increased adsorption of the albumin to the modified surface.
      In vitro cytocompatibility evaluation revealed that silanization improved cell
      growth on AZ91 modified by silane S1. Measurement of the concentration of Mg2+
      ions released during the cell culture indicated that silanization does not affect
      substrate degradation.

PMID- 27877542
TI  - Biodegradable organic acid-crosslinked alkali-treated gelatins with anti
      thrombogenic and endothelialization properties.
AB  - Gelatins were crosslinked with organic acids and treated with alkali to impart to
      them endothelialization and anti-thrombogenic properties. These matrices were
      characterized by biochemical and physicochemical techniques. The amounts of
      residual amino groups in the matrices decreased with increasing crosslinker
      concentration. The matrices with the highest crosslinking densities showed
      excellent endothelial cell adhesion and proliferation. In addition, the adhesion
      of platelets and formation of fibrin networks on the matrices were suppressed
      with increasing crosslinker concentration. The matrices also exhibited excellent
      biodegradability, and the degradation rate decreased with increasing crosslinking
      density. All the organic acid-crosslinked alkali-treated gelatins showed
      excellent anti-thrombogenic and endothelialization properties, superior to those
      of glutaraldehyde-crosslinked alkali-treated gelatins.

PMID- 27877543
TI  - Comparisons of immersion and electrochemical properties of highly biocompatible
      Ti-15Zr-4Nb-4Ta alloy and other implantable metals for orthopedic implants.
AB  - Metal release from implantable metals and the properties of oxide films formed on
      alloy surfaces were analyzed, focusing on the highly biocompatible Ti-15Zr-4Nb
      4Ta alloy. The thickness and electrical resistance (Rp) of the oxide film on such
      an alloy were compared with those of other implantable metals. The quantity of
      metal released during a 1-week immersion test was considerably smaller for the Ti
      15Zr-4Nb-4Ta than the Ti-6Al-4V alloy. The potential (E10) indicating a current
      density of 10 MUA cm-2 estimated from the anodic polarization curve was
      significantly higher for the Ti-15Zr-4Nb-4Ta than the Ti-6Al-4V alloy and other
      metals. Moreover, the oxide film (4-7 nm thickness) formed on the Ti-15Zr-4Nb-4Ta
      surface is electrochemically robust. The oxide film mainly consisted of TiO2 with
      small amounts of ZrO2, Nb2O5 and Ta2O5 that made the film electrochemically
      stable. The Rp of Ti-15Zr-4Nb-4Ta was higher than that of Ti-6Al-4V, i.e. 0.9
      Omega cm2 in 0.9% NaCl and 1.3 Omega cm2 in Eagle's medium. This Rp was
      approximately five-fold higher than that of stainless steel, which has a history
      of more than 40 years of clinical use in the human body. Ti-15Zr-4Nb-4Ta is a
      potential implant material for long-term clinical use. Moreover, E10 and Rp were
      found to be useful parameters for assessing biological safety.

PMID- 27877544
TI  - Chondrocyte spheroids on microfabricated PEG hydrogel surface and their
      noninvasive functional monitoring.
AB  - A two-dimensional microarray of 10 000 (100 * 100) chondrocyte spheroids was
      constructed with a 100 MUm spacing on a micropatterned gold electrode that was
      coated with poly(ethylene glycol) (PEG) hydrogels. The PEGylated surface as a
      cytophobic region was regulated by controlling the gel structure through
      photolithography. In this way, a PEG hydrogel was modulated enough to inhibit
      outgrowth of chondrocytes from a cell adhering region in the horizontal
      direction, which is critical for inducing formation of three-dimensional
      chondrocyte aggregations (spheroids) within 24 h. We further report noninvasive
      monitoring of the cellular functional change at the cell membrane using a
      chondrocyte-based field effect transistor. This measurement is based on detection
      of extracellular potential change induced as a result of the interaction between
      extracellular matrix protein secreted from spheroid and substrate at the cell
      membrane. The interface potential change at the cell membrane/gate interface can
      be monitored during the differentiation of spheroids without any labeling
      materials. Our measurements of the time evolution of the interface potential
      provide important information for understanding the uptake kinetics for cellular
      differentiation.

PMID- 27877545
TI  - Nickel-free stainless steel avoids neointima formation following coronary stent
      implantation.
AB  - SUS316L stainless steel and cobalt-chromium and platinum-chromium alloys are
      widely used platforms for coronary stents. These alloys also contain nickel (Ni),
      which reportedly induces allergic reactions in some subjects and is known to have
      various cellular effects. The effects of Ni on neointima formation after stent
      implantation remain unknown, however. We developed coronary stents made of Ni
      free high-nitrogen austenitic stainless steel prepared using a N2-gas pressurized
      electroslag remelting (P-ESR) process. Neointima formation and inflammatory
      responses following stent implantation in porcine coronary arteries were then
      compared between the Ni-free and SUS316L stainless steel stents. We found
      significantly less neointima formation and inflammation in arteries implanted
      with Ni-free stents, as compared to SUS316L stents. Notably, Ni2+ was eluted into
      the medium from SUS316L but not from Ni-free stainless steel. Mechanistically,
      Ni2+ increased levels of hypoxia inducible factor protein-1alpha (HIF-1alpha) and
      its target genes in cultured smooth muscle cells. HIF-1alpha and their target
      gene levels were also increased in the vascular wall at SUS316L stent sites but
      not at Ni-free stent sites. The Ni-free stainless steel coronary stent reduces
      neointima formation, in part by avoiding activation of inflammatory processes via
      the Ni-HIF pathway. The Ni-free-stainless steel stent is a promising new coronary
      stent platform.

PMID- 27877547
TI  - Editorial.

PMID- 27877548
TI  - Recent global trends in structural materials research.

PMID- 27877546
TI  - Effectiveness and biocompatibility of a novel biological adhesive application for
      repair of meniscal tear on the avascular zone.
AB  - We have investigated the effectiveness and safety of a newly developed biological
      adhesive for repair of meniscal tear. The adhesive was composed of disuccinimidyl
      tartrate (DST) as a crosslinker and human serum albumin (HSA) as a hardener. To
      determine adequate concentration, bonding strength was measured using a
      tensiometer 5 min after applying the adhesive on the avascular zone tear of
      porcine meniscus; it was compared with the strengths of commercially available
      cyanoacrylate-based and fibrin-based adhesives. In vivo examination was performed
      using Japanese white rabbits, creating longitudinal tears on the avascular zone
      of meniscus and applying DST-HSA adhesive. Three months after operation the
      rabbits were sacrificed and tension test and histological evaluation were
      performed. Bonding strength was measured in three porcine meniscus groups: (i)
      only suturing, (ii) suturing after applying the adhesive on surface and (iii)
      suturing using an adhesive-soaked suture. The optimum concentrations were 0.1
      mmol of DST and 42 w/v% of HAS. Bonding strength was greatest with cyanoacrylate
      based adhesive, followed by DST-HSA adhesive, and fibrin-based adhesive. No
      inflammation was observed in the synovium or surrounding tissues 3 months after
      using the DST-HSA adhesive. Bonding strength was greatest with DST-HSA adhesive
      soaked suturing group (77 +/- 6 N), followed by suturing only group (61 +/- 5 N)
      and surface adhesive application group (60 +/- 8 N). The newly developed DST-HSA
      adhesive is considered safe and may be effective in enforcement of bonding of
      avascular zone tear of the meniscus.

PMID- 27877549
TI  - Hydrogen detection in metals: a review and introduction of a Kelvin probe
      approach.
AB  - Hydrogen in materials is an important topic for many research fields in materials
      science. Hence in the past quite a number of different techniques for determining
      the amount of hydrogen in materials and for measuring hydrogen permeation through
      them have been developed. Some of these methods have found widespread
      application. But for many problems the achievable sensitivity is usually not high
      enough and ready-to-use techniques providing also good spatial resolution,
      especially in the submicron range, are very limited, and mostly not suitable for
      widespread application. In this work this situation will be briefly reviewed and
      a novel scanning probe technique based method introduced.

PMID- 27877550
TI  - The first bulk nanostructured metal.
AB  - Nanotechnology has become an overused adjective, but there has been justified
      excitement in the context of structural materials. A class of iron alloys has
      been discovered in which a high density of strong interfaces can be created by
      heat-treatment alone. The packing of interfaces is so large, and the fact that
      there is an intrinsic work hardening mechanism in the structure, leads to
      remarkable properties. The genesis of this structure, its commercialization, the
      new science associated with the discovery, and its limitations are all explored
      in this short review.

PMID- 27877551
TI  - Creep behavior and in-depth microstructural characterization of dissimilar
      joints.
AB  - The 700  degrees C power plants currently under development will utilize Ni-base
      alloys such as alloy 617 for components to be operated at temperatures >650 
      degrees C. Due to economic reasons for components or parts of components which
      are subjected to temperatures <650  degrees C, 2% Cr or 9-12% Cr steels is used,
      depending on the required mechanical properties. This makes the dissimilar
      joining of Ni-base alloys and Cr steels a necessity in these plants. Experimental
      investigations show that these joints have to be identified as weak points with
      regard to damage development under creep and creep-fatigue loading. The present
      investigation focuses on welds between the alloy 617 and 2% Cr steel. Under creep
      load the fracture occurs near the fusion line between the 2% Cr steel base metal
      and alloy 617 weld metal. To explain the reasons for this fracture location, the
      microstructure of this fusion line was investigated using TEM and FIB techniques
      after welding and after creep loading. The TEM investigations have shown a small
      zone in the weld metal near the fusion line exhibiting chromium depletion and
      clearly reduced amounts of chromium carbides, leading to a weakening of this
      zone.

PMID- 27877552
TI  - Deformation behavior of duplex austenite and epsilon-martensite high-Mn steel.
AB  - Deformation and work hardening behavior of Fe-17Mn-0.02C steel containing epsilon
      martensite within the austenite matrix have been investigated by means of in situ
      microstructural observations and x-ray diffraction analysis. During deformation,
      the steel shows the deformation-induced transformation of austenite -> epsilon
      martensite -> alpha'-martensite as well as the direct transformation of austenite
      -> alpha'-martensite. Based on the calculation of changes in the fraction of each
      constituent phase, we found that the phase transformation of austenite -> epsilon
      martensite is more effective in work hardening than that of epsilon-martensite ->
      alpha'-martensite. Moreover, reverse transformation of epsilon-martensite ->
      austenite has also been observed during deformation. It originates from the
      formation of stacking faults within the deformed epsilon-martensite, resulting in
      the formation of 6H-long periodic ordered structure.

PMID- 27877553
TI  - Fe-Al-Mn-C lightweight structural alloys: a review on the microstructures and
      mechanical properties.
AB  - Adding a large amount of light elements such as aluminum to steels is not a new
      concept recalling that several Fe-Al-Mn-C alloys were patented in 1950s for
      replacement of nickel or chromium in corrosion resistance steels. However, the so
      called lightweight steels or low-density steels were revisited recently, which is
      driven by demands from the industry where steel has served as a major structural
      material. Strengthening without loss of ductility has been a triumph in steel
      research, but lowering the density of steel by mixing with light elements will be
      another prospect that may support the competitiveness against emerging
      alternatives such as magnesium alloys. In this paper, we review recent studies on
      lightweight steels, emphasizing the concept of alloy design for microstructures
      and mechanical properties. The influence of alloying elements on the phase
      constituents, mechanical properties and the change of density is critically
      reviewed. Deformation mechanisms of various lightweight steels are discussed as
      well. This paper provides a reason why the success of lightweight steels is
      strongly dependent on scientific achievements even though alloy development is
      closely related to industrial applications. Finally, we summarize some of the
      main directions for future investigations necessary for vitalizing this field of
      interest.

PMID- 27877555
TI  - A thermo-mechanical correlation with driving forces for hcp martensite and twin
      formations in the Fe-Mn-C system exhibiting multicomposition sets.
AB  - The thermodynamic properties of the Fe-Mn-C system were investigated by using an
      analytical model constructed by a CALPHAD approach. The stacking fault energy
      (SFE) of the fcc structure with respect to the hcp phase was always constant at
      T0, independent of the composition and temperature when other related parameters
      were assumed to be constant. Experimental limits for the thermal hcp formation
      and the mechanical (deformation-induced) hcp formation were separated by the SFE
      at T0. The driving force for the fcc to hcp transition, defined as a
      dimensionless value -dGm/(RT), was determined in the presence of Fe-rich and Mn
      rich composition sets in each phase. Carbon tended to partition to the Mn-rich
      phase rather than to the Fe-rich phase for the compositions studied. The results
      obtained revealed a thermo-mechanical correlation with empirical yield strength,
      maximum true stress and maximum true strain. The proportionality between
      thermodynamics and mechanical properties is discussed.

PMID- 27877554
TI  - Advanced three-dimensional electron microscopy techniques in the quest for better
      structural and functional materials.
AB  - After a short review of electron tomography techniques for materials science,
      this overview will cover some recent results on different shape memory and
      nanostructured metallic systems obtained by various three-dimensional (3D)
      electron imaging techniques. In binary Ni-Ti, the 3D morphology and distribution
      of Ni4Ti3 precipitates are investigated by using FIB/SEM slice-and-view yielding
      3D data stacks. Different quantification techniques will be presented including
      the principal ellipsoid for a given precipitate, shape classification following a
      Zingg scheme, particle distribution function, distance transform and water
      penetration. The latter is a novel approach to quantifying the expected matrix
      transformation in between the precipitates. The different samples investigated
      include a single crystal annealed with and without compression yielding layered
      and autocatalytic precipitation, respectively, and a polycrystal revealing
      different densities and sizes of the precipitates resulting in a multistage
      transformation process. Electron tomography was used to understand the
      interaction between focused ion beam-induced Frank loops and long dislocation
      structures in nanobeams of Al exhibiting special mechanical behaviour measured by
      on-chip deposition. Atomic resolution electron tomography is demonstrated on Ag
      nanoparticles in an Al matrix.

PMID- 27877556
TI  - Microstructure and cleavage in lath martensitic steels.
AB  - In this paper we discuss the microstructure of lath martensitic steels and the
      mechanisms by which it controls cleavage fracture. The specific experimental
      example is a 9Ni (9 wt% Ni) steel annealed to have a large prior austenite grain
      size, then examined and tested in the as-quenched condition to produce a
      relatively coarse lath martensite. The microstructure is shown to approximate the
      recently identified 'classic' lath martensite structure: prior austenite grains
      are divided into packets, packets are subdivided into blocks, and blocks contain
      interleaved laths whose variants are the two Kurjumov-Sachs relations that share
      the same Bain axis of the transformation. When the steel is fractured in brittle
      cleavage, the laths in the block share {100} cleavage planes and cleave as a
      unit. However, cleavage cracks deflect or blunt at the boundaries between blocks
      with different Bain axes. It follows that, as predicted, the block size governs
      the effective grain size for cleavage.

PMID- 27877557
TI  - Nanoscale structure and atomic disorder in the iron-based chalcogenides.
AB  - The multiband iron-based superconductors have layered structure with a phase
      diagram characterized by a complex interplay of charge, spin and lattice
      excitations, with nanoscale atomic structure playing a key role in their
      fundamental electronic properties. In this paper, we briefly review nanoscale
      structure and atomic disorder in iron-based chalcogenide superconductors. We
      focus on the Fe(Se,S)1-x Te x (11-type) and K0.8Fe1.6Se2 (122-type) systems,
      discussing their local structure obtained by extended x-ray absorption fine
      structure. Local structure studies on the Fe(Se,S)1-x Te x system reveal clear
      nanoscale phase separation characterized by coexisting components of different
      atomic configurations, similar to the case of random alloys. In fact, the Fe-Se/S
      and Fe-Te distances in the ternary Fe(Se,S)1-x Te x are found to be closer to the
      respective distances in the binary FeSe/FeS and FeTe systems, showing significant
      divergence of the local structure from the average one. The observed features are
      characteristic of ternary random alloys, indicating breaking of the local
      symmetry in these materials. On the other hand, K0.8Fe1.6Se2 is known for phase
      separation in an iron-vacancy ordered phase and an in-plane compressed lattice
      phase. The local structure of these 122-type chalcogenides shows that this system
      is characterized by a large local disorder. Indeed, the experiments suggest a
      nanoscale glassy phase in K0.8Fe1.6Se2, with the superconductivity being similar
      to the granular materials. While the 11-type structure has no spacer layer, the
      122-type structure contains intercalated atoms unlike the 1111-type REFeAsO (RE =
      rare earth) oxypnictides, having well-defined REO spacer layers. It is clear that
      the interlayer atomic correlations in these iron-based superconducting structures
      play an important role in structural stability as well as superconductivity and
      magnetism.

PMID- 27877558
TI  - Recent advances in beta-FeSe1-x and related superconductors.
AB  - It has been more than four years since the discovery of beta-FeSe1-x
      superconductors. Through the efforts of many outstanding research groups,
      unprecedented advances in the field have been achieved. High-quality single
      crystals of beta-FeSe1-x and related compounds have been prepared by various
      techniques, allowing us to explore in detail the physical properties of this
      class of materials. Detailed characterizations of the structure and properties of
      these crystals have helped us to understand the origin of superconductivity in
      beta-FeSe1-x . The occurrence of superconductivity is associated with the low
      temperature structure distortion, which is accompanied by several anomalies.
      Recent measurements on quasiparticle and acoustic phonon dynamics with respect to
      the orbital modification in beta-FeSe1-x suggest the opening of an energy gap
      below 130-140 K, accompanied by a coincident transfer of optical spectral weight
      in the visible range and alterations in transport properties. These observations
      provide convincing evidence that the modification of the electronic structure
      occurs prior to the lattice distortion. They further suggest that the high
      temperature gap and the lattice symmetry breaking are driven by short-range
      orbital and/or charge orders.

PMID- 27877559
TI  - Systematic studies of tannin-formaldehyde aerogels: preparation and properties.
AB  - Gelation of tannin-formaldehyde (TF) solutions was systematically investigated by
      changing pH and concentration of TF resin in water. In this way we constructed
      the TF phase diagram, from which chemical hydrogels could be described, and also
      synthesized thermoreversible tannin-based hydrogels. Conditions of non-gelation
      were also determined. Hydrogels were dried in supercritical CO2, leading to a
      broad range of TF aerogels. The latter were investigated for volume shrinkage,
      total porosity, micro-, meso- and macropore volumes, Brunauer-Emmett-Teller (BET)
      surface area, microscopic texture, mechanical and thermal properties. All these
      properties are discussed in relation to each other, leading to an accurate and
      self-consistent description of these bioresource-based highly porous materials.
      The conditions for obtaining the highest BET surface area or mesopore volume were
      determined and explained in relation to the preparation conditions. The highest
      BET surface area, 880 m2 g-1, is remarkably high for organic aerogels derived
      from a natural resource.

PMID- 27877561
TI  - Synthesis of Au microwires by selective oxidation of Au-W thin-film composition
      spreads.
AB  - We report on the stress-induced growth of Au microwires out of a surrounding Au-W
      matrix by selective oxidation, in view of a possible application as 'micro
      Velcro'. The Au wires are extruded due to the high compressive stress in the
      tungsten oxide formed by oxidation of elemental W. The samples were fabricated as
      a thin-film materials library using combinatorial sputter deposition followed by
      thermal oxidation. Sizes and shapes of the Au microwires were investigated as a
      function of the W to Au ratio. The coherence length and stress state of the Au
      microwires were related to their shape and plastic deformation. Depending on the
      composition of the Au-W precursor, the oxidized samples showed regions with
      differently shaped Au microwires. The Au48W52 composition yielded wires with the
      maximum length to diameter ratio due to the high compressive stress in the
      tungsten oxide matrix. The values of wire length (35 MUm) and diameter (2 MUm)
      achieved at the Au48W52 composition are suitable for micro-Velcro applications.

PMID- 27877560
TI  - Micrometer-level naked-eye detection of caesium particulates in the solid state.
AB  - Large amounts of radioactive material were released from the Fukushima Daiichi
      nuclear plant in Japan, contaminating the local environment. During the early
      stages of such nuclear accidents, iodine I-131 (half-life 8.02 d) is usually
      detectable in the surrounding atmosphere and bodies of water. On the other hand,
      in the long-term, soil and water contamination by Cs-137, which has a half-life
      of 30.17 years, is a serious problem. In Japan, the government is planning and
      carrying out radioactive decontamination operations not only with public agencies
      but also non-governmental organizations, making radiation measurements within
      Japan. If caesium (also radiocaesium) could be detected by the naked eye then its
      environmental remediation would be facilitated. Supramolecular material
      approaches, such as host-guest chemistry, are useful in the design of high
      resolution molecular sensors and can be used to convert molecular-recognition
      processes into optical signals. In this work, we have developed molecular
      materials (here, phenols) as an optical probe for caesium cation-containing
      particles with implementation based on simple spray-on reagents and a commonly
      available fluorescent lamp for naked-eye detection in the solid state. This
      chemical optical probe provides a higher spatial resolution than existing
      radioscopes and gamma-ray cameras.

PMID- 27877562
TI  - Local strains, calorimetry, and magnetoresistance in adaptive martensite
      transition in multiple nanostrips of Ni39+x Mn50Sn11-x (x ? 2) alloys.
AB  - Ni39+x Mn50Sn11-x (x = 0.5, 1.0, 1.5 and 2) alloys comprise multiple martensite
      nanostrips of nanocrystallites when cast in small discs, for example, ~15 mm
      diameter and 8 mm width. A single martensite phase with a L10 tetragonal crystal
      structure at room temperature can be formed at a critical Sn content of 9.0 at.%
      (x = 2), whereas an austenite cubic L21 phase turns up at smaller x ? 1.5. The
      decrease in the Sn content from x = 2 to 0.5 also results in a gradual increase
      in the crystallite size from 11 to 17 nm. Scanning electron microscopy images
      reveal arrays of regularly displaced multiple martensite strips (x ? 1.5) with an
      average thickness of 20 nm. As forced oscillators, these strips carry over the
      local strains, magnetic dipoles, and thermions simultaneously in a martensite
      austenite (or reverse) phase transition. A net residual enthalpy change DeltaHM<
      >A = -0.12 J g-1 arises in the process that lacks reversibility between the
      cooling and heating cycles. A large magnetoresistance of (-)26% at 10 T is
      observed together with a large entropy change of 11.8 mJ g-1 K-1, nearly twice
      the value ever reported in such alloys, in the isothermal magnetization at 311 K.
      The DeltaHM<->A irreversibility accounts for a thermal hysteresis in the
      electrical resistivity. Strain induced in the martensite strips leads them to
      have a higher electrical resistivity than that of the higher-temperature
      austenite phase. A model considering time-dependent enthalpy relaxation explains
      the irreversibility features.

PMID- 27877563
TI  - Generation of microgrooved silica nanotube membranes with sustained drug delivery
      and cell contact guidance ability by using a Teflon microfluidic chip.
AB  - Silica nanotubes have been extensively applied in the biomedical field. However,
      very little attention has been paid to the fabrication and application of
      micropatterned silica nanotubes. In the present study, microgrooved silica
      nanotube membranes were fabricated in situ by microgrooving silica-coated
      collagen hybrid fibril hydrogels in a Teflon microfluidic chip followed by
      calcination for removal of collagen fibrils. Scanning electron microscopy images
      showed that the resulting silica nanotube membranes displayed a typical
      microgroove/ridge surface topography with ~50 MUm microgroove width and ~120 MUm
      ridge width. They supported adsorption of bone morphogenetic protein 2 (BMP-2)
      and exhibited a sustained release behavior for BMP-2. After culturing with
      osteoblast MC3T3-E1 cells, they induced an enhanced osteoblast differentiation
      due to the release of biologically active BMP-2 and a strong contact guidance
      ability to directly align and elongate osteoblasts due to the presence of
      microgrooved surface topography, indicating their potential application as a
      multi-functional cell-supporting matrix for tissue generation.

PMID- 27877564
TI  - Layered rare-earth hydroxide and oxide nanoplates of the Y/Tb/Eu system: phase
      controlled processing, structure characterization and color-tunable
      photoluminescence via selective excitation and efficient energy transfer.
AB  - Well-crystallized (Y0.97-x Tb0.03Eu x )2(OH)5NO3.nH2O (x = 0-0.03) layered rare
      earth hydroxide (LRH) nanoflakes of a pure high-hydration phase have been
      produced by autoclaving from the nitrate/NH4OH reaction system under the
      optimized conditions of 100  degrees C and pH ~7.0. The flakes were then
      converted into (Y0.97-x Tb0.03Eu x )2O3 phosphor nanoplates with color-tunable
      photoluminescence. Detailed structural characterizations confirmed that LRH solid
      solutions contained NO3- anions intercalated between the layers. Characteristic
      Tb3+ and Eu3+ emissions were detected in the ternary LRHs by selectively exciting
      the two types of activators, and the energy transfer from Tb3+ to Eu3+ was
      observed. Annealing the LRHs at 1100  degrees C produced cubic-lattice (Y0.97-x
      Tb0.03Eu x )2O3 solid-solution nanoplates with exposed 222 facets. Multicolor,
      intensity-adjustable luminescence was attained by varying the excitation
      wavelength from ~249 nm (the charge transfer excitation band of Eu3+) to 278 nm
      (the 4f8-4f75d1 transition of Tb3+). Unitizing the efficient Tb3+ to Eu3+ energy
      transfer, the emission color of (Y0.97-x Tb0.03Eu x )2O3 was tuned from
      approximately green to yellowish-orange by varying the Eu3+/Tb3+ ratio. At the
      optimal Eu3+ content of x = 0.01, the efficiency of energy transfer was ~91% and
      the transfer mechanism was suggested to be electric multipole interactions. The
      phosphor nanoplates developed in this work may be incorporated in luminescent
      films and find various lighting and display applications.

PMID- 27877566
TI  - Role of toll-like receptors 3, 4 and 7 in cellular uptake and response to
      titanium dioxide nanoparticles.
AB  - Innate immune response is believed to be among the earliest provisional cellular
      responses, and mediates the interactions between microbes and cells. Toll-like
      receptors (TLRs) are critical to these interactions. We hypothesize that TLRs
      also play an important role in interactions between nanoparticles (NPs) and
      cells, although little information has been reported concerning such an
      interaction. In this study, we investigated the role of TLR3, TLR4 and TLR7 in
      cellular uptake of titanium dioxide NP (TiO2 NP) agglomerates and the resulting
      inflammatory responses to these NPs. Our data indicate that TLR4 is involved in
      the uptake of TiO2 NPs and promotes the associated inflammatory responses. The
      data also suggest that TLR3, which has a subcellular location distinct from that
      of TLR4, inhibits the denaturation of cellular protein caused by TiO2 NPs. In
      contrast, the unique cellular localization of TLR7 has middle-ground functional
      roles in cellular response after TiO2 NP exposure. These findings are important
      for understanding the molecular interaction mechanisms between NPs and cells.

PMID- 27877565
TI  - Determination of the surface band bending in In x Ga1-x N films by hard x-ray
      photoemission spectroscopy.
AB  - Core-level and valence band spectra of In x Ga1-x N films were measured using
      hard x-ray photoemission spectroscopy (HX-PES). Fine structure, caused by the
      coupling of the localized Ga 3d and In 4d with N 2s states, was experimentally
      observed in the films. Because of the large detection depth of HX-PES (~20 nm),
      the spectra contain both surface and bulk information due to the surface band
      bending. The In x Ga1-x N films (x = 0-0.21) exhibited upward surface band
      bending, and the valence band maximum was shifted to lower binding energy when
      the mole fraction of InN was increased. On the other hand, downward surface band
      bending was confirmed for an InN film with low carrier density despite its n-type
      conduction. Although the Fermi level (EF) near the surface of the InN film was
      detected inside the conduction band as reported previously, it can be concluded
      that EF in the bulk of the film must be located in the band gap below the
      conduction band minimum.

PMID- 27877567
TI  - In vitro and in vivo evaluation of electrospun PCL/PMMA fibrous scaffolds for
      bone regeneration.
AB  - Scaffolds were fabricated by electrospinning using polycaprolactone (PCL) blended
      with poly(methyl methacrylate) (PMMA) in ratios of 10/0, 7/3, 5/5 and 3/7. The
      PCL/PMMA ratio affected the fiber diameter, contact angle, tensile strength and
      biological in vitro and in vivo properties of the scaffolds, and the 7/3 ratio
      resulted in a higher mechanical strength than 5/5 and 3/7. In vitro cytotoxicity
      and proliferation of MG-63 osteoblast cells on these blended scaffolds were
      examined by MTT assay, and it was found that PCL/PMMA blends are suitable for
      osteoblast cell proliferation. Confocal images and expression of proliferating
      cell nuclear antigen confirmed the good proliferation and expression of cells on
      the 7/3 PCL/PMMA fibrous scaffolds. In vivo bone formation was examined using rat
      models, and bone formation was observed on the 7/3 PCL/PMMA scaffold within 2
      months. In vitro and in vivo results suggest that 7/3 PCL/PMMA scaffolds can be
      used for bone tissue regeneration.

PMID- 27877570
TI  - Ab initio identified design principles of solid-solution strengthening in Al.
AB  - Solid-solution strengthening in six Al-X binary systems is investigated using
      first-principle methods. The volumetric mismatch parameter and the solubility
      enthalpy per solute were calculated. We derive three rules for designing solid
      solution strengthened alloys: (i) the solubility enthalpy per solute is related
      to the volumetric mismatch by a power law; (ii) for each annealing temperature,
      there exists an optimal solute-volume mismatch to achieve maximum strength; and
      (iii) the strengthening potential of high volumetric mismatch solutes is severely
      limited by their low solubility. Our results thus show that the thermodynamic
      properties of the system (here Al-X alloys) set clear upper bounds to the
      achievable strengthening effects owing to the reduced solubility with increasing
      volume mismatch.

PMID- 27877569
TI  - Oxide-based inorganic/organic and nanoporous spherical particles: synthesis and
      functional properties.
AB  - This paper reviews the recent progress in the preparation of oxide-based and
      heteroatom-doped particles. Surfactant-templated oxide particles, e.g. silica and
      titania, are possible candidates for various potential applications such as
      adsorbents, photocatalysts, and optoelectronic and biological materials. We
      highlight nanoporous oxides of one element, such as silicon or titanium, and
      those containing multiple elements, which exhibit properties that are not
      achieved with individual components. Although the multicomponent nanoporous
      oxides possess a number of attractive functions, the origin of their properties
      is hard to determine due to compositional/structural complexity. Particles with a
      well-defined size and shape are keys for a quantitative and detailed discussion
      on the unique complex properties of the particles. From this viewpoint, we review
      the synthesis techniques of the oxide particles, which are functionalized with
      organic molecules or doped with heteroatoms, the physicochemical properties of
      the particles and the possibilities for their photofunctional applications as
      complex systems.

PMID- 27877568
TI  - Dispersion and surface functionalization of oxide nanoparticles for transparent
      photocatalytic and UV-protecting coatings and sunscreens.
AB  - This review describes recent efforts on the synthesis, dispersion and surface
      functionalization of the three dominating oxide nanoparticles used for
      photocatalytic, UV-blocking and sunscreen applications: titania, zinc oxide, and
      ceria. The gas phase and liquid phase synthesis is described briefly and examples
      are given of how weakly aggregated photocatalytic or UV-absorbing oxide
      nanoparticles with different composition, morphology and size can be generated.
      The principles of deagglomeration are reviewed and the specific challenges for
      nanoparticles highlighted. The stabilization of oxide nanoparticles in both
      aqueous and non-aqueous media requires a good understanding of the magnitude of
      the interparticle forces and the surface chemistry of the materials. Quantitative
      estimates of the Hamaker constants in various media and measurements of the
      isoelectric points for the different oxide nanoparticles are presented together
      with an overview of different additives used to prepare stable dispersions. The
      structural and chemical requirements and the various routes to produce
      transparent photocatalytic and nanoparticle-based UV-protecting coatings, and UV
      blocking sunscreens are described and discussed.

PMID- 27877571
TI  - Fretting fatigue behaviour of Ni-free high-nitrogen stainless steel in a
      simulated body fluid.
AB  - Fretting fatigue behaviour of Ni-free high-nitrogen steel (HNS) with a yield
      strength of about 800 MPa, which was prepared by nitrogen gas pressurized
      electroslag remelting, was studied in air and in phosphate-buffered saline (PBS(
      )). For comparison, fretting fatigue behaviour of cold-rolled SUS316L steel
      (SUS316L(CR)) with similar yield strength was examined. The plain fatigue limit
      of HNS was slightly lower than that of SUS316L(CR) although the former had a
      higher tensile strength than the latter. The fretting fatigue limit of HNS was
      higher than that of SUS316L(CR) both in air and in PBS(-). A decrease in fatigue
      limit of HNS by fretting was significantly smaller than that of SUS316L(CR) in
      both environments, indicating that HNS has better fretting fatigue resistance
      than SUS316L(CR). The decrease in fatigue limit by fretting is discussed taking
      into account the effect of friction stress due to fretting and the additional
      influences of wear, tribocorrosion and plastic deformation in the fretted area.

PMID- 27877572
TI  - One-pot synthesis of magnetic, macro/mesoporous bioactive glasses for bone tissue
      engineering.
AB  - Magnetic and macro/mesoporous bioactive glasses were synthesized by a one-pot
      method via a handy salt leaching technique. It was identified to be an effective
      and simple synthetic strategy. The non-ionic triblock copolymer, poly(ethylene
      glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P123), was used
      as the structure directing agent for mesoporous structure but also as the
      reductant to reduce the iron source into magnetic iron oxide. The prepared
      materials exhibited excellent super-paramagnetic property with interconnected
      macroporous (200-300 MUm) and mesoporous (3.4 nm) structure. Furthermore, their
      outstanding drug storage/release properties and rapid (5) induction of
      hydroxyapatite growth ability were investigated after immersing in simulated body
      fluid solution at 37  degrees C. Notably, the biocompatibility assessment
      confirmed that the materials obtained presented good biocompatibility and
      enhanced adherence of HeLa cells. Herein, the novel materials are expected to
      have potential application for bone tissue engineering.

PMID- 27877573
TI  - Nitrogen in chromium-manganese stainless steels: a review on the evaluation of
      stacking fault energy by computational thermodynamics.
AB  - Nitrogen in austenitic stainless steels and its effect on the stacking fault
      energy (SFE) has been the subject of intense discussions in the literature. Until
      today, no generally accepted method for the SFE calculation exists that can be
      applied to a wide range of chemical compositions in these systems. Besides
      different types of models that are used from first-principle to thermodynamics
      based approaches, one main reason is the general lack of experimentally measured
      SFE values for these steels. Moreover, in the respective studies, not only
      different alloying systems but also different domains of nitrogen contents were
      analyzed resulting in contrary conclusions on the effect of nitrogen on the SFE.
      This work gives a review on the current state of SFE calculation by computational
      thermodynamics for the Fe-Cr-Mn-N system. An assessment of the thermodynamic
      effective Gibbs free energy, [Formula: see text], model for the [Formula: see
      text] phase transformation considering existing data from different literature
      and commercial databases is given. Furthermore, we introduce the application of a
      non-constant composition-dependent interfacial energy, b gamma/epsilon , required
      to consider the effect of nitrogen on SFE in these systems.

PMID- 27877574
TI  - Nanocomposite for methanol oxidation: synthesis and characterization of cubic Pt
      nanoparticles on graphene sheets.
AB  - We present our recent results on Pt nanoparticles on graphene sheets (Pt-NPs/G),
      a nanocomposite prepared with microwave assistance in ionic liquid 2
      hydroxyethanaminiumformate. Preparation of Pt-NPs/G was achieved without the
      addition of extra reductant such as hydrazine or ethylene glycol. The Pt
      nanoparticles on graphene have a cubic-like shape (about 60 wt% Pt loading, Pt
      NPs/G) and the particle size is 6 +/- 3 nm from transmission electron microscopy
      results. Electrochemical cyclic voltammetry studies in 0.5 M aqueous H2SO4 were
      performed using Pt-NPs/G and separately, for comparison, using a commercially
      available electrocatalyst (60 wt% Pt loading, Pt/C). The electrochemical surface
      ratio of Pt-NPs/G to Pt/C is 0.745. The results of a methanol oxidation reaction
      (MOR) in 0.5 M aqueous H2SO4 + 1.0 M methanol for the two samples are presented.
      The MOR results show that the ratios of the current density of oxidation (If) to
      the current density of reduction (Ib) are 3.49 (Pt-NPs/G) and 1.37 (Pt/C),
      respectively, with a preference by 2.55 times favoring Pt-NPs/G. That is, the
      tolerance CO poisoning of Pt-NPs/G is better than that of commercial Pt/C.

PMID- 27877575
TI  - Tissue-engineered endothelial cell layers on surface-modified Ti for inhibiting
      in vitro platelet adhesion.
AB  - A tissue-engineered endothelial layer was prepared by culturing endothelial cells
      on a fibroblast growth factor-2 (FGF-2)-l-ascorbic acid phosphate magnesium salt
      n-hydrate (AsMg)-apatite (Ap) coated titanium plate. The FGF-2-AsMg-Ap coated Ti
      plate was prepared by immersing a Ti plate in supersaturated calcium phosphate
      solutions supplemented with FGF-2 and AsMg. The FGF-2-AsMg-Ap layer on the Ti
      plate accelerated proliferation of human umbilical vein endothelial cells
      (HUVECs), and showed slightly higher, but not statistically significant, nitric
      oxide release from HUVECs than on as-prepared Ti. The endothelial layer
      maintained proper function of the endothelial cells and markedly inhibited in
      vitro platelet adhesion. The tissue-engineered endothelial layer formed on the
      FGF-2-AsMg-Ap layer is promising for ameliorating platelet activation and
      thrombus formation on cardiovascular implants.

PMID- 27877576
TI  - Probing the electronic properties of ternary A n M3n-1B2n (n = 1: A = Ca, Sr; M =
      Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity.
AB  - We follow the evolution of the electronic properties of the titled homologous
      series when n as well as the atomic type of A and M are varied where for n = 1, A
      = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal
      structure of n = 1 members is known to be CaRh2B2-type (Fddd), while that of n =
      3 is Ca3Rh8B6-type (Fmmm); the latter can be visualized as a stacking of
      structural fragments from AM3B2 (P6/mmm) and AM2B2. The metallic properties of
      the n = 1 and 3 members are distinctly different: on the one hand, the n = 1
      members are characterized by a linear coefficient of the electronic specific heat
      gamma ~ 3 mJ mol-1 K-2, a Debye temperature thetaD ~ 300 K, a normal conductivity
      down to 2 K and a relatively strong linear magnetoresistivity for fields up to
      150 kOe. The n = 3 family, on the other hand, exhibits gamma ~ 18 mJ mol-1 K-2,
      thetaD ~ 330 K, a weak linear magnetoresistivity and an onset of
      superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8
      B6, Tc = 3.4 K and Hc2 ~ 4.0 kOe). These remarkable differences are consistent
      with the findings of the electronic band structures and density of state (DOS)
      calculations. In particular, satisfactory agreement between the measured and
      calculated gamma was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies
      at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a
      local valley: this is the main reason behind the differences between the, e.g.,
      superconducting properties. Finally, although all atoms contribute to the DOS at
      EF, the contribution of the Rh atoms is the strongest.

PMID- 27877577
TI  - Highly conductive interwoven carbon nanotube and silver nanowire transparent
      electrodes.
AB  - Electrodes fabricated using commercially available silver nanowires (AgNWs) and
      single walled carbon nanotubes (SWCNTs) produced sheet resistances in the range 4
      24 Omega ?-1 with specular transparencies up to 82 %. Increasing the aqueous
      dispersibility of SWCNTs decreased the bundle size present in the film resulting
      in improved SWCNT surface dispersion in the films without compromising
      transparency or sheet resistance. In addition to providing conduction pathways
      between the AgNW network, the SWCNTs also provide structural support, creating
      stable self-supporting films. Entanglement of the AgNWs and SWCNTs was
      demonstrated to occur in solution prior to deposition by monitoring the
      transverse plasmon resonance mode of the AgNWs during processing. The interwoven
      AgNW/SWCNT structures show potential for use in optoelectronic applications as
      transparent electrodes and as an ITO replacement.

PMID- 27877578
TI  - Sb-mediated Ge quantum dots in Ti-oxide-Si diode: negative differential
      capacitance.
AB  - The negative differential capacitance (NDC) effect is observed on a titanium
      oxide-silicon structure, formed on n-type silicon with embedded germanium quantum
      dots (QDs). The Ge QDs were grown by an Sb-mediated technique. The NDC effect was
      observed for temperatures below 200 K. We found that approximately six to eight
      electrons can be trapped in the valence band states of Ge QDs. We explain the NDC
      effect in terms of the emission of electrons from valence band states in the very
      narrow QD layer under reverse bias.

PMID- 27877579
TI  - Extruded blend films of poly(vinyl alcohol) and polyolefins: common and hard
      elastic nanostructure evolution in the polyolefin during straining as monitored
      by SAXS.
AB  - Straining of PVA/PE and PVA/PP blends (70:30) is monitored by small-angle x-ray
      scattering (SAXS). Sheet-extruded films with different predraw ratio are
      investigated. The discrete SAXS of predrawn samples originates from polyolefin
      nanofibrils inside of polyolefin microfibrils immersed in a PVA matrix. PE
      nanofibrils deform less than the macroscopic strain without volume change. PP
      nanofibrils experience macroscopic strain. They lengthen but their diameter does
      not decrease. This is explained by strain-induced crystallization of PP from an
      amorphous depletion shell around the core of the nanofibril. The undrawn PVA/PE
      film exhibits isotropic semicrystalline nanostructure. Undrawn PVA/PP holds PP
      droplets containing oriented stacks of semicrystalline PP like neat precursors of
      hard-elastic thermoplasts. Respective predrawn films are softer than the undrawn
      material, indicating conversion into the hard-elastic state. Embedding of the
      polyolefin significantly retards neck formation. The polyolefin microfibrils can
      easily be extracted from the water-soluble matrix.

PMID- 27877580
TI  - 18O-tracer diffusion along nanoscaled Sc2O3/yttria stabilized zirconia (YSZ)
      multilayers: on the influence of strain.
AB  - The oxygen tracer diffusion coefficient describing transport along nano
      /microscaled YSZ/Sc2O3 multilayers as a function of the thick-ness of the ion
      conducting YSZ layers has been measured by isotope exchange depth profiling
      (IEDP), using secondary ion mass spec-trometry (SIMS). The multilayer samples
      were prepared by pulsed laser deposition (PLD) on (0001) Al2O3 single crystalline
      substrates. The values for the oxygen tracer diffusion coefficient were analyzed
      as a combination of contributions from bulk and interface contributions and
      compared with results from YSZ/Y2O3-multilayers with similar microstructure.
      Using the Nernst-Einstein equation as the relation between diffusivity and
      electrical conductivity we find very good agreement between conductivity and
      diffusion data, and we exclude substantial electronic conductivity in the
      multilayers. The effect of hetero-interface transport can be well explained by a
      simple interface strain model. As the multilayer samples consist of columnar film
      crystallites with a defined inter-face structure and texture, we also discuss the
      influence of this particular microstructure on the interfacial strain.

PMID- 27877581
TI  - Evolution of the tetragonal to rhombohedral transition in (1 - x)(Bi1/2Na1/2)TiO3
      - xBaTiO3 (x <= 7%).
AB  - (1 - x)(Bi1/2Na1/2)TiO3 - xBaTiO3 has been the most studied Pb-free piezoelectric
      material in the last decade; however, puzzles still remain about its phase
      transitions, especially around the important morphotropic phase boundary (MPB).
      By introducing the strain glass transition concept from the ferroelastic field,
      it was found that the phase transition from tetragonal (T, P4bm) to rhombohedral
      (R, R3c) was affected by a strain glass transition at higher temperature for x ?
      4%. In these compositions, the T-R transition was delayed or even totally
      suppressed and displayed huge thermal hysteresis upon cooling and heating. Also,
      isothermal phase transitions were predicted and realized successfully in the
      crossover region, where the interaction between the T-R transition and the strain
      glass transition was strong. Our results revealed the strain glass nature in
      compositions around the MPB in this important material, and also provide new
      clues for understanding the transition complexity in other (Bi1/2Na1/2)TiO3-based
      Pb-free piezoelectric materials.

PMID- 27877583
TI  - Nanomaterials and nanofabrication for biomedical applications.

PMID- 27877582
TI  - Influence of surface features on the adhesion of Staphylococcus epidermidis to Ag
      TiCN thin films.
AB  - Staphylococcus epidermidis has emerged as one of the major nosocomial pathogens
      associated with infections of implanted medical devices. The initial adhesion of
      these organisms to the surface of biomaterials is assumed to be an important
      stage in their colonization. The main objective of this work is to assess the
      influence of surface features on the adhesion of S. epidermidis to Ag-TiCN
      coatings deposited by dc reactive magnetron sputtering. The structural results
      obtained by x-ray diffraction show that the coatings crystallize in a B1-NaCl
      crystal structure typical of TiC0.3N0.7. The increase of Ag content promoted the
      formation of Ag crystalline phases. According to the results obtained with atomic
      force microscopy, a decrease on the surface roughness of the films from 39 to 7
      nm is observed as the Ag content increases from 0 to 15 at.%. Surface energy
      results show that the increase of Ag promotes an increase in hydrophobicity.
      Bacterial adhesion and biofilm formation on coatings were assessed by the
      enumeration of the number of viable cells. The results showed that the surface
      with lower roughness and higher hydrophobicity leads to greater bacterial
      adhesion and biofilm formation, highlighting that surface morphology and
      hydrophobicity rule the colonization of materials.

PMID- 27877584
TI  - Synthesis of MoS2 and MoO2 for their applications in H2 generation and lithium
      ion batteries: a review.
AB  - Scientists increasingly witness the applications of MoS2 and MoO2 in the field of
      energy conversion and energy storage. On the one hand, MoS2 and MoO2 have been
      widely utilized as promising catalysts for electrocatalytic or photocatalytic
      hydrogen evolution in aqueous solution. On the other hand, MoS2 and MoO2 have
      also been verified as efficient electrode material for lithium ion batteries. In
      this review, the synthesis, structure and properties of MoS2 and MoO2 are briefly
      summarized according to their applications for H2 generation and lithium ion
      batteries. Firstly, we overview the recent advancements in the morphology control
      of MoS2 and MoO2 and their applications as electrocatalysts for hydrogen
      evolution reactions. Secondly, we focus on the photo-induced water splitting for
      H2 generation, in which MoS2 acts as an important co-catalyst when combined with
      other semiconductor catalysts. The newly reported research results of the
      significant functions of MoS2 nanocomposites in photo-induced water splitting are
      presented. Thirdly, we introduce the advantages of MoS2 and MoO2 for their
      enhanced cyclic performance and high capacity as electrode materials of lithium
      ion batteries. Recent key achievements in MoS2- and MoO2-based lithium ion
      batteries are highlighted. Finally, we discuss the future scope and the important
      challenges emerging from these fascinating materials.

PMID- 27877585
TI  - Solid State Ionics: from Michael Faraday to green energy-the European dimension.
AB  - Solid State Ionics has its roots essentially in Europe. First foundations were
      laid by Michael Faraday who discovered the solid electrolytes Ag2S and PbF2 and
      coined terms such as cation and anion, electrode and electrolyte. In the 19th and
      early 20th centuries, the main lines of development toward Solid State Ionics,
      pursued in Europe, concerned the linear laws of transport, structural analysis,
      disorder and entropy and the electrochemical storage and conversion of energy.
      Fundamental contributions were then made by Walther Nernst, who derived the
      Nernst equation and detected ionic conduction in heterovalently doped zirconia,
      which he utilized in his Nernst lamp. Another big step forward was the discovery
      of the extraordinary properties of alpha silver iodide in 1914. In the late 1920s
      and early 1930s, the concept of point defects was established by Yakov Il'ich
      Frenkel, Walter Schottky and Carl Wagner, including the development of point
      defect thermodynamics by Schottky and Wagner. In terms of point defects, ionic
      (and electronic) transport in ionic crystals became easy to visualize. In an
      'evolving scheme of materials science', point disorder precedes structural
      disorder, as displayed by the AgI-type solid electrolytes (and other ionic
      crystals), by ion-conducting glasses, polymer electrolytes and nano-composites.
      During the last few decades, much progress has been made in finding and
      investigating novel solid electrolytes and in using them for the preservation of
      our environment, in particular in advanced solid state battery systems, fuel
      cells and sensors. Since 1972, international conferences have been held in the
      field of Solid State Ionics, and the International Society for Solid State Ionics
      was founded at one of them, held at Garmisch-Partenkirchen, Germany, in 1987.

PMID- 27877586
TI  - The influence of different nanostructured scaffolds on fibroblast growth.
AB  - Skin serves as a protective barrier, modulating body temperature and waste
      discharge. It is therefore desirable to be able to repair any damage that occurs
      to the skin as soon as possible. In this study, we demonstrate a relatively easy
      and cost-effective method for the fabrication of nanostructured scaffolds, to
      shorten the time taken for a wound to heal. Various scaffolds consisting of
      nanohemisphere arrays of poly(lactic-co-glycolic acid) (PLGA), polylactide and
      chitosan were fabricated by casting using a nickel (Ni) replica mold. The Ni
      replica mold is electroformed using the highly ordered nanohemisphere array of
      the barrier-layer surface of an anodic aluminum oxide membrane as the template.
      Mouse fibroblast cells (L929s) were cultured on the nanostructured polymer
      scaffolds to investigate the effect of these different nanohemisphere arrays on
      cell proliferation. The concentration of collagen type I on each scaffold was
      then measured through enzyme-linked immunosorbent assay to find the most
      effective scaffold for shortening the wound-healing process. The experimental
      data indicate that the proliferation of L929 is superior when a nanostructured
      PLGA scaffold with a feature size of 118 nm is utilized.

PMID- 27877587
TI  - pH-responsive polymeric micelles with core-shell-corona architectures as
      intracellular anti-cancer drug carriers.
AB  - Polymeric micelles with core-shell-corona nanoarchitecture were designed for
      intracellular therapeutic anti-cancer drug carriers. Poly(styrene-b-acrylic acid
      b-ethylene glycol) (PS-b-PAA-b-PEG) asymmetric triblock copolymer underwent self
      assembly in aqueous solution to form spherical micelles with hydrophobic PS core,
      anionic PAA shell and hydrophilic PEG corona. The anti-cancer drug (doxorubicin,
      DOX) was successfully incorporated into the polymeric micelles. The in vitro
      release experiment confirmed that the release of DOX from the micelles was
      inhibited at pH 7.4. In contrast, an accelerated release of DOX was observed at
      mildly acidic conditions such as pH 4.5. The excellent biocompatibility of our PS
      b-PAA-b-PEG-based micelles made the synthesized nano-carrier best suited for the
      delivery of anti-cancer drugs.

PMID- 27877589
TI  - Paper-based tuberculosis diagnostic devices with colorimetric gold nanoparticles.
AB  - A colorimetric sensing strategy employing gold nanoparticles and a paper assay
      platform has been developed for tuberculosis diagnosis. Unmodified gold
      nanoparticles and single-stranded detection oligonucleotides are used to achieve
      rapid diagnosis without complicated and time-consuming thiolated or other surface
      modified probe preparation processes. To eliminate the use of sophisticated
      equipment for data analysis, the color variance for multiple detection results
      was simultaneously collected and concentrated on cellulose paper with the data
      readout transmitted for cloud computing via a smartphone. The results show that
      the 2.6 nM tuberculosis mycobacterium target sequences extracted from patients
      can easily be detected, and the turnaround time after the human DNA is extracted
      from clinical samples was approximately 1 h.

PMID- 27877588
TI  - Accelerated colorimetric immunosensing using surface-modified porous monoliths
      and gold nanoparticles.
AB  - A rapid and sensitive immunoassay platform integrating polymerized monoliths and
      gold nanoparticles (AuNPs) has been developed. The porous monoliths are
      photopolymerized in situ within a silica capillary and serve as solid support for
      high-mass transport and high-density capture antibody immobilization to create a
      shorter diffusion length for antibody-antigen interactions, resulting in a rapid
      assay and low reagent consumption. AuNPs are modified with detection antibodies
      and are utilized as signals for colorimetric immunoassays without the need for
      enzyme, substrate and sophisticated equipment for quantitative measurements. This
      platform has been verified by performing a human IgG sandwich immunoassay with a
      detection limit of 0.1 ng ml-1. In addition, a single assay can be completed in 1
      h, which is more efficient than traditional immunoassays that require several
      hours to complete.

PMID- 27877590
TI  - Prussian blue nanoparticles as nanocargoes for delivering DNA drugs to cancer
      cells.
AB  - We studied the use of Prussian blue nanoparticles (PBNPs) as novel nanocarriers
      for sending DNA drugs into cancer cells. 11-mercaptoundecanoic acid (MUA) was
      used to functionalize the surfaces of PBNPs (nanocubes with an average dimension
      of 75 nm) for subsequent covalent grafting of a 33-mer DNA drug with a FAM
      reporter at the 3' end. The PBNPs synthesis and DNA drug conjugation were
      characterized by transmission electron microscopy (TEM) and Fourier-transform
      infrared absorption (FTIR), respectively. The drug was a decoy
      oligodeoxynucleotide (dODN) that inhibits the signal transducer and activator of
      transcription 3 (STAT3). The DNA-PBNPs drug (dODN@MUA-PBNPs) was delivered into
      human prostate carcinoma 22rv1 cells by endocytosis in vitro as confirmed by
      confocal fluorescence microscopy. MTT cell viability assays were carried out to
      assess the effect of the DNA-PBNPs drug. The results showed that the dODN
      molecules were successfully conjugated to the MUA modified PBNPs via amide and/or
      disulfide bond formation and could thus be successfully delivered into the cancer
      cells. The control experiments showed that the unconjugated dODN molecules were
      not able to enter the cancer cells no matter whether non-functionalized PBNPs
      were present or not. It was also found that the DNA-PBNPs drugs were internalized
      and then distributed homogeneously throughout the cell, including cytoplasmic and
      nucleic regions, after endocytosis. The cancer cell-killing ability increased
      with the amount of dODN conjugated on PBNPs and the dosage of DNA-PBNPs drug
      internalized.

PMID- 27877591
TI  - Probing cellular behaviors through nanopatterned chitosan membranes.
AB  - This paper describes a high-throughput method for developing physically modified
      chitosan membranes to probe the cellular behavior of MDCK epithelial cells and
      HIG-82 fibroblasts adhered onto these modified membranes. To prepare chitosan
      membranes with micro/nanoscaled features, we have demonstrated an easy-to-handle,
      facile approach that could be easily integrated with IC-based manufacturing
      processes with mass production potential. These physically modified chitosan
      membranes were observed by scanning electron microscopy to gain a better
      understanding of chitosan membrane surface morphology. After MDCK cells and HIG
      82 fibroblasts were cultured on these modified chitosan membranes for various
      culture durations (i.e. 1, 2, 4, 12 and 24 h), they were investigated to decipher
      cellular behavior. We found that both cells preferred to adhere onto a flat
      surface rather than on a nanopatterned surface. However, most (> 80%) of the MDCK
      cells showed rounded morphology and would suspend in the cultured medium instead
      of adhering onto the planar surface of negatively nanopatterned chitosan
      membranes. This means different cell types (e.g. fibroblasts versus epithelia)
      showed distinct capabilities/preferences of adherence for materials of varying
      surface roughness. We also showed that chitosan membranes could be re-used at
      least nine times without significant contamination and would provide us
      consistency for probing cell-material interactions by permitting reuse of the
      same substrate. We believe these results would provide us better insight into
      cellular behavior, specifically, microscopic properties and characteristics of
      cells grown under unique, nanopatterned cell-interface conditions.

PMID- 27877593
TI  - Using crosslinkable diacetylene phospholipids to construct two-dimensional packed
      beds in supported lipid bilayer separation platforms.
AB  - Separating and purifying cell membrane-associated biomolecules has been a
      challenge owing to their amphiphilic property. Taking these species out of their
      native lipid membrane environment usually results in biomolecule degradation. One
      of the new directions is to use supported lipid bilayer (SLB) platforms to
      separate the membrane species while they are protected in their native
      environment. Here we used a type of crosslinkable diacetylene phospholipids,
      diynePC (1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine), as a packed
      material to create a 'two-dimensional (2D) packed bed' in a SLB platform. After
      the diynePC SLB is exposed to UV light, some of the diynePC lipids in the SLB can
      crosslink and the non-crosslinked monomer lipids can be washed away, leaving a 2D
      porous solid matrix. We incorporated the lipid vesicle deposition method with a
      microfluidic device to pattern the location of the packed-bed region and the feed
      region with species to be separated in a SLB platform. Our atomic force
      microscopy result shows that the nano-scaled structure density of the '2D packed
      bed' can be tuned by the UV dose applied to the diynePC membrane. When the model
      membrane biomolecules were forced to transport through the packed-bed region,
      their concentration front velocities were found to decrease linearly with the UV
      dose, indicating the successful creation of packed obstacles in these 2D lipid
      membrane separation platforms.

PMID- 27877594
TI  - Room temperature redox reaction by oxide ion migration at carbon/Gd-doped CeO2
      heterointerface probed by an in situ hard x-ray photoemission and soft x-ray
      absorption spectroscopies.
AB  - In situ hard x-ray photoemission spectroscopy (HX-PES) and soft x-ray absorption
      spectroscopy (SX-XAS) have been employed to investigate a local redox reaction at
      the carbon/Gd-doped CeO2 (GDC) thin film heterointerface under applied dc bias.
      In HX-PES, Ce3d and O1s core levels show a parallel chemical shift as large as
      3.2 eV, corresponding to the redox window where ionic conductivity is
      predominant. The window width is equal to the energy gap between donor and
      acceptor levels of the GDC electrolyte. The Ce M-edge SX-XAS spectra also show a
      considerable increase of Ce3+ satellite peak intensity, corresponding to
      electrochemical reduction by oxide ion migration. In addition to the reversible
      redox reaction, two distinct phenomena by the electrochemical transport of oxide
      ions are observed as an irreversible reduction of the entire oxide film by O2
      evolution from the GDC film to the gas phase, as well as a vigorous precipitation
      of oxygen gas at the bottom electrode to lift off the GDC film. These in situ
      spectroscopic observations describe well the electrochemical polarization
      behavior of a metal/GDC/metal capacitor-like two-electrode cell at room
      temperature.

PMID- 27877595
TI  - Exchange coupling controlled ferrite with dual magnetic resonance and broad
      frequency bandwidth in microwave absorption.
AB  - Ti-doped barium ferrite powders BaFe12-x Ti x O19 (x = 0, 0.2, 0.3, 0.4, 0.5,
      0.6, 0.7 and 0.8) were synthesized by the sol-gel method. The phase structure and
      morphology were analyzed by x-ray diffraction (XRD) and scanning electron
      microscopy, respectively. The powders were also studied for their magnetic
      properties and microwave absorption. Results show that the Ti-doped barium
      ferrites (BFTO) exist in single phase and exhibit hexagonal plate-like structure.
      The anisotropy field Ha of the BFTO decreases almost linearly with the increase
      in Ti concentration, which leads to a shift of the natural resonance peak toward
      low frequency. Two natural resonance peaks appear, which can be assigned to the
      double values of the Lande factor g that are found to be ~2.0 and ~2.3 in the
      system and can be essentially attributed to the existence of Fe3+ ions and the
      exchange coupling effect between Fe3+ and Fe2+ ions, respectively. Such a dual
      resonance effect contributes a broad magnetic loss peak and thus a high
      attenuation constant, and leads to a dual reflection loss (RL) peak over the
      frequency range between 26.5 and 40 GHz. The high attenuation constants are
      between 350 and 500 at peak position. The optimal RL reaches around -45 dB and
      the practicable frequency bandwidth is beyond 11 GHz. This suggests that the BFTO
      powders could be used as microwave absorbing materials with extraordinary
      properties.

PMID- 27877596
TI  - Nanoscale magneto-structural coupling in as-deposited and freestanding single
      crystalline Fe7Pd3 ferromagnetic shape memory alloy thin films.
AB  - Ferromagnetic shape memory alloys are characterized by strong magneto-mechanical
      coupling occurring at the atomic scale causing large magnetically inducible
      strains at the macroscopic level. Employing combined atomic and magnetic force
      microscopy studies at variable temperature, we systematically explore the
      relation between the magnetic domain pattern and the underlying structure for as
      deposited and freestanding single-crystalline Fe7Pd3 thin films across the
      martensite-austenite transition. We find experimental evidence that magnetic
      domain appearance is strongly affected by the presence and absence of
      nanotwinning. While the martensite-austenite transition upon temperature
      variation of as-deposited films is clearly reflected in topography by the
      presence and absence of a characteristic surface corrugation pattern, the
      magnetic domain pattern is hardly affected. These findings are discussed
      considering the impact of significant thermal stresses arising in the austenite
      phase. Freestanding martensitic films reveal a hierarchical structure of micro-
      and nanotwinning. The associated domain organization appears more complex, since
      the dominance of magnetic energy contributors alters within this length scale
      regime.

PMID- 27877592
TI  - Non-metallic nanomaterials in cancer theranostics: a review of silica- and carbon
      based drug delivery systems.
AB  - The rapid development in nanomaterials has brought great opportunities to cancer
      theranostics, which aims to combine diagnostics and therapy for cancer treatment
      and thereby improve the healthcare of patients. In this review we focus on the
      recent progress of several cancer theranostic strategies using mesoporous silica
      nanoparticles and carbon-based nanomaterials. Silicon and carbon are both group
      IV elements; they have been the most abundant and significant non-metallic
      substances in human life. Their intrinsic physical/chemical properties are of
      critical importance in the fabrication of multifunctional drug delivery systems.
      Responsive nanocarriers constructed using these nanomaterials have been promising
      in cancer-specific theranostics during the past decade. In all cases, either a
      controlled texture or the chemical functionalization is coupled with adaptive
      properties, such as pH-, light-, redox- and magnetic field- triggered responses.
      Several studies in cells and mice models have implied their underlying
      therapeutic efficacy; however, detailed and long-term in vivo clinical
      evaluations are certainly required to make these bench-made materials compatible
      in real bedside circumstances.

PMID- 27877597
TI  - Anisotropic mobility and carrier dynamics in the beta-type BEDT-TTF salts as
      studied by inter-layer transverse magnetoresistance.
AB  - A new method to estimate an in-plane conduction anisotropy in a quasi-two
      dimensional (q2D) layered conductor by measuring the inter-layer transverse
      magnetoresistance is proposed. We applied this method to layered organic
      conductors beta-(BEDT-TTF)2X (BEDT-TTF = bis(ethylenedithio)tetrathiafulvalene,
      C10H8S8; X = IBr2, I2Br) by applying magnetic field rotating within the basal
      plane at 4.2 K. We found the anisotropic behaviour of carrier mobility MU. From
      this, anomalous distribution of carrier lifetime tau on the Fermi surface is
      derived, by the use of Fermi surface data reported for the materials.
      Calculations of the non-uniform susceptibility chi0( q ) suggest that carrier
      scattering is enhanced at specific k -points related to partial nesting of the
      Fermi surface. The present method is thus demonstrated to be an efficient
      experimental tool to elucidate anisotropic carrier dynamics in q2D conductors.

PMID- 27877599
TI  - Intrinsic stability of ferroelectric and piezoelectric properties of epitaxial
      PbZr0.45Ti0.55O3 thin films on silicon in relation to grain tilt.
AB  - Piezoelectric thin films of PbZr0.45Ti0.55O3 were grown on Si substrates in four
      different ways, resulting in different crystalline structures, as determined by x
      ray analysis. The crystalline structures were different in the spread in tilt
      angle and the in-plane alignment of the crystal planes between different grains.
      It is found that the deviations of the ferroelectric polarization loop from that
      of the ideal rectangular loop (reduction of the remanent polarization with
      respect to the saturation polarization, dielectric constant of the film, slanting
      of the loop, coercive field value) all scale with the average tilt angle. A model
      is derived based on the assumption that the tilted grain boundaries between
      grains affect the film properties locally. This model describes the observed
      trends. The effective piezoelectric coefficient d33,eff shows also a weak
      dependence on the average tilt angle for films grown in a single layer, whereas
      it is strongly reduced for the films deposited in multiple layers. The least
      affected properties are obtained for the most epitaxial films, i.e. grown on a
      SrTiO3 epitaxial seed layer, by pulsed laser deposition. These films are
      intrinsically stable and do not require poling to acquire these stable
      properties.

PMID- 27877598
TI  - Preparation of chitosan/mesoporous silica nanoparticle composite hydrogels for
      sustained co-delivery of biomacromolecules and small chemical drugs.
AB  - We have developed composite hydrogels of chitosan (CS) and mesoporous silica
      nanoparticles (MSNs) in this study. The gelation rate, gel strength, drug
      delivery behavior and chondrocyte proliferation properties were investigated. The
      introduction of MSNs into CS accelerated the gelation process at body temperature
      and also increased the elastic modulus G' from 1000 to 1800 Pa. When we used
      gentamicin (GS) and bovine serum albumin (BSA) as model small chemical drugs and
      biomacromolecules, respectively, the CS/MSN hydrogels released GS and BSA in a
      sustained manner simultaneously, but the CS hydrogels only showed sustained BSA
      release. Furthermore, in vitro chondrocyte culture showed that the CS/MSN
      composite hydrogels indeed performed much better in supporting chondrocyte growth
      and maintaining chondrocytic phenotype compared to the CS hydrogels. Therefore,
      the results suggest that the CS/MSN composite hydrogels can be potentially very
      useful for cartilage regeneration.

PMID- 27877600
TI  - Preparation of a hierarchically porous AlPO4 monolith via an epoxide-mediated sol
      gel process accompanied by phase separation.
AB  - Monolithic aluminum phosphate (AlPO4) with a macro-mesoporous structure has been
      successfully prepared via the sol-gel process accompanied by phase separation in
      the presence of poly(ethylene oxide) (PEO). Gelation of the system has been
      mediated by propylene oxide (PO), while PEO induces a phase separation. The dried
      gel is amorphous, whereas the crystalline tridymite phase precipitates upon
      heating above 1000  degrees C. Heat treatment does not spoil the macroporous
      morphology of the AlPO4 monoliths. Nitrogen adsorption-desorption measurements
      revealed that the skeletons of the dried gels possess a mesostructure with a
      median pore size of about 30 nm and a surface area as high as 120 m2 g-1.
      Hydrothermal treatment before heat treatment can increase the surface area to 282
      m2 g-1.

PMID- 27877601
TI  - Biosilicate(r)-gelatine bone scaffolds by the foam replica technique: development
      and characterization.
AB  - The development of bioactive glass-ceramic materials has been a topic of great
      interest aiming at enhancing the mechanical strength of traditional bioactive
      scaffolds. In the present study, we test and demonstrate the use of
      Biosilicate(r) glass-ceramic powder to fabricate bone scaffolds by the foam
      replica method. Scaffolds possessing the main requirements for use in bone tissue
      engineering (95% porosity, 200-500 MUm pore size) were successfully produced.
      Gelatine coating was investigated as a simple approach to increase the mechanical
      competence of the scaffolds. The gelatine coating did not affect the
      interconnectivity of the pores and did not significantly affect the bioactivity
      of the Biosilicate(r) scaffold. The gelatine coating significantly improved the
      compressive strength (i.e. 0.80 +/- 0.05 MPa of coated versus 0.06 +/- 0.01 MPa
      of uncoated scaffolds) of the Biosilicate(r) scaffold. The combination of
      Biosilicate(r) glass-ceramic and gelatine is attractive for producing novel
      scaffolds for bone tissue engineering.

PMID- 27877602
TI  - Role of a disperse carbon interlayer on the performances of tandem a-Si solar
      cells.
AB  - We report the effect of a disperse carbon interlayer between the n-a-Si:H layer
      and an aluminium zinc oxide (AZO) back contact on the performance of amorphous
      silicon solar cells. Carbon was incorporated to the AZO film as revealed by x-ray
      photoelectron spectroscopy and energy-dispersive x-ray analysis. Solar cells
      fabricated on glass substrates using AZO in the back contact performed better
      when a disperse carbon interlayer was present in their structure. They exhibited
      an initial efficiency of 11%, open-circuit voltage Voc = 1.6 V, short-circuit
      current JSC = 11 mA cm-2 and a filling factor of 63%, that is, a 10% increase in
      the JSC and 20% increase in the efficiency compared to a standard solar cell.

PMID- 27877604
TI  - The development of Ce3+-activated (Gd,Lu)3Al5O12 garnet solid solutions as
      efficient yellow-emitting phosphors.
AB  - Ce3+-activated Gd3Al5O12 garnet, effectively stabilized by Lu3+ doping, has been
      developed for new yellow-emitting phosphors. The powder processing of [(Gd1-x Lu
      x ) 1-y Ce y ]3Al5O12 solid solutions was achieved through precursor synthesis
      via carbonate precipitation, followed by annealing. The resultant (Gd,Lu)AG:Ce3+
      phosphor particles exhibit typical yellow emission at ~570 nm (5d-4f transition
      of Ce3+) upon blue-light excitation at ~457 nm (the 2F5/2-5d transition of Ce3+).
      The quenching concentration of Ce3+ was determined to be ~1.0 at% (y = 0.01) and
      the quenching mechanism was suggested to be driven by exchange interactions. The
      best luminescent [(Gd0.9Lu0.1)0.99Ce0.01]AG phosphor is comparative to the well
      known YAG:Ce3+ in emission intensity but has a substantially red-shifted emission
      band that is desired for warm-white lighting. The effects of processing
      temperature (1000-1500  degrees C) on the spectroscopic properties of the
      phosphors, especially those of Lu3+/Ce3+, were thoroughly investigated and
      discussed from the centroid position and crystal field splitting of the Ce3+ 5d
      energy levels.

PMID- 27877603
TI  - Bi-layered calcium phosphate cement-based composite scaffold mimicking natural
      bone structure.
AB  - In this study, a core/shell bi-layered calcium phosphate cement (CPC)-based
      composite scaffold with adjustable compressive strength, which mimicked the
      structure of natural cortical/cancellous bone, was fabricated. The dense tubular
      CPC shell was prepared by isostatic pressing CPC powder with a specially designed
      mould. A porous CPC core with unidirectional lamellar pore structure was
      fabricated inside the cavity of dense tubular CPC shell by unidirectional freeze
      casting, followed by infiltration of poly(lactic-co-glycolic acid) and
      immobilization of collagen. The compressive strength of bi-layered CPC-based
      composite scaffold can be controlled by varying thickness ratio of dense layer to
      porous layer. Compared to the scaffold without dense shell, the pore
      interconnection of bi-layered scaffold was not obviously compromised because of
      its high unidirectional interconnectivity but poor three dimensional
      interconnectivity. The in vitro results showed that the rat bone marrow stromal
      cells attached and proliferated well on the bi-layered CPC-based composite
      scaffold. This novel bi-layered CPC-based composite scaffold is promising for
      bone repair.

PMID- 27877605
TI  - Nanotechnology in the regulation of stem cell behavior.
AB  - Stem cells are known for their potential to repair damaged tissues. The adhesion,
      growth and differentiation of stem cells are likely controlled by the surrounding
      microenvironment which contains both chemical and physical cues. Physical cues in
      the microenvironment, for example, nanotopography, were shown to play important
      roles in stem cell fate decisions. Thus, controlling stem cell behavior by
      nanoscale topography has become an important issue in stem cell biology.
      Nanotechnology has emerged as a new exciting field and research from this field
      has greatly advanced. Nanotechnology allows the manipulation of sophisticated
      surfaces/scaffolds which can mimic the cellular environment for regulating
      cellular behaviors. Thus, we summarize recent studies on nanotechnology with
      applications to stem cell biology, including the regulation of stem cell
      adhesion, growth, differentiation, tracking and imaging. Understanding the
      interactions of nanomaterials with stem cells may provide the knowledge to apply
      to cell-scaffold combinations in tissue engineering and regenerative medicine.

PMID- 27877607
TI  - A comparative study of the chondrogenic potential between synthetic and natural
      scaffolds in an in vivo bioreactor.
AB  - The clinical demand for cartilage tissue engineering is potentially large for
      reconstruction defects resulting from congenital deformities or degenerative
      disease due to limited donor sites for autologous tissue and donor site
      morbidities. Cartilage tissue engineering has been successfully applied to the
      medical field: a scaffold pre-cultured with chondrocytes was used prior to
      implantation in an animal model. We have developed a surgical approach in which
      tissues are engineered by implantation with a vascular pedicle as an in vivo
      bioreactor in bone and adipose tissue engineering. Collagen type II, chitosan,
      poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) were four
      commonly applied scaffolds in cartilage tissue engineering. To expand the
      application of the same animal model in cartilage tissue engineering, these four
      scaffolds were selected and compared for their ability to generate cartilage with
      chondrocytes in the same model with an in vivo bioreactor. Gene expression and
      immunohistochemistry staining methods were used to evaluate the chondrogenesis
      and osteogenesis of specimens. The result showed that the PLGA and PCL scaffolds
      exhibited better chondrogenesis than chitosan and type II collagen in the in vivo
      bioreactor. Among these four scaffolds, the PCL scaffold presented the most
      significant result of chondrogenesis embedded around the vascular pedicle in the
      long-term culture incubation phase.

PMID- 27877606
TI  - A microfluidic paper-based electrochemical biosensor array for multiplexed
      detection of metabolic biomarkers.
AB  - Paper-based microfluidic devices have emerged as simple yet powerful platforms
      for performing low-cost analytical tests. This paper reports a microfluidic paper
      based electrochemical biosensor array for multiplexed detection of
      physiologically relevant metabolic biomarkers. Different from existing paper
      based electrochemical devices, our device includes an array of eight
      electrochemical sensors and utilizes a handheld custom-made electrochemical
      reader (potentiostat) for signal readout. The biosensor array can detect several
      analytes in a sample solution and produce multiple measurements for each analyte
      from a single run. Using the device, we demonstrate simultaneous detection of
      glucose, lactate and uric acid in urine, with analytical performance comparable
      to that of the existing commercial and paper-based platforms. The paper-based
      biosensor array and its electrochemical reader will enable the acquisition of
      high-density, statistically meaningful diagnostic information at the point of
      care in a rapid and cost-efficient way.

PMID- 27877608
TI  - Promotion of osteogenic differentiation of stem cells and increase of bone
      bonding ability in vivo using urease-treated titanium coated with calcium
      phosphate and gelatin.
AB  - Because of its excellent biocompatibility and low allergenicity, titanium has
      been widely used for bone replacement and tissue engineering. To produce a
      desirable composite with enhanced bone response and mechanical strength, in this
      study bioactive calcium phosphate (CaP) and gelatin composites were coated onto
      titanium (Ti) via a novel urease technique. The cellular responses to the
      CaP/gelatin/Ti (CaP/gel/Ti) and bone bonding ability were evaluated with
      proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) on
      CaP/gel/Ti and CaP/Ti in vitro. The results showed that the optical density
      values, alkaline phosphatase expression and genes expression of MSCs on
      CaP/gel/Ti were similar to those on CaP/Ti, yet significantly higher than those
      on pure Ti (p < 0.05). CaP/gel/Ti and CaP/Ti rods (2 mm in diameter, 10 mm in
      length) were also implanted into femoral shaft of rabbits and pure Ti rods served
      as control (n = 10). Histological examination, scanning electron microscopy (SEM)
      and energy dispersive spectroscopy (EDS) measurements were performed at 4 and 8
      weeks after the operation. The histological and SEM observations demonstrated
      clearly that more new bone formed on the surface of CaP/gel/Ti than in the other
      two groups at each time point. The CaP/gel/Ti bonded to the surrounding bone
      directly with no intervening soft tissue layer. An interfacial layer, containing
      Ti, Ca and P, was found to form at the interface between bone and the implant on
      all three groups by EDS analysis. However, the content of Ca, P in the surface of
      CaP/gel/Ti implants was more than in the other two groups at each time point. The
      CaP/gel/Ti modified by the urease method was not only beneficial for MSCs
      proliferation and osteogenic differentiation, but also favorable for bone bonding
      ability on Ti implants in vivo, suggesting that Ti functionalized with CaP and
      gelatin might have a great potential in clinical joint replacement or dental
      implants.

PMID- 27877609
TI  - Correlation between properties and microstructure of laser sintered porous beta
      tricalcium phosphate bone scaffolds.
AB  - A porous beta-tricalcium phosphate (beta-TCP) bioceramic scaffold was
      successfully prepared with our homemade selective laser sintering system.
      Microstructure observation by a scanning electron microscope showed that the
      grains grew from 0.21 to 1.32 MUm with the decrease of laser scanning speed from
      250 to 50 mm min-1. The mechanical properties increased mainly due to the
      improved apparent density when the laser scanning speed decreased to 150 mm min
      1. When the scanning speed was further decreased, the grain size became larger
      and the mechanical properties severely decreased. The highest Vickers hardness
      and fracture toughness of the scaffold were 3.59 GPa and 1.16 MPa m1/2,
      respectively, when laser power was 11 W, spot size was 1 mm in diameter, layer
      thickness was 0.1-0.2 mm and laser scanning speed was 150 mm min-1. The
      biocompatibility of these scaffolds was assessed in vitro with MG63 osteoblast
      like cells and human bone marrow mesenchymal stem cells. The results showed that
      all the prepared scaffolds are suitable for cell attachment and differentiation.
      Moreover, the smaller the grain size, the better the cell biocompatibility. The
      porous scaffold with a grain size of 0.71 MUm was immersed in a simulated body
      fluid for different days to assess the bioactivity. The surface of the scaffold
      was covered by a bone-like apatite layer, which indicated that the beta-TCP
      scaffold possesses good bioactivity. These discoveries demonstrated the evolution
      rule between grain microstructure and the properties that give a useful reference
      for the fabrication of beta-TCP bone scaffolds.

PMID- 27877610
TI  - Alkaline earth lead and tin compounds Ae2Pb, Ae2Sn, Ae = Ca, Sr, Ba, as
      thermoelectric materials.
AB  - We present a detailed theoretical study of three alkaline earth compounds Ca2Pb,
      Sr2Pb and Ba2Pb, which have undergone little previous study, calculating
      electronic band structures and Boltzmann transport and bulk moduli using density
      functional theory. We also study the corresponding tin compounds Ca2Sn, Sr2Sn and
      Ba2Sn. We find that these are all narrow band gap semiconductors with an
      electronic structure favorable for thermoelectric performance, with substantial
      thermopowers for the lead compounds at temperature ranges from 300 to 800 K. For
      the lead compounds, we further find very low calculated bulk moduli-roughly half
      of the values for the lead chalcogenides, suggestive of soft phonons and hence
      low lattice thermal conductivity. All these facts indicate that these materials
      merit experimental investigation as potential high performance thermoelectrics.
      We find good potential for thermoelectric performance in the environmentally
      friendly stannide materials, particularly at high temperature.

PMID- 27877611
TI  - Thermal stability and phase transformations of martensitic Ti-Nb alloys.
AB  - Aiming at understanding the governing microstructural phenomena during heat
      treatments of Ni-free Ti-based shape memory materials for biomedical
      applications, a series of Ti-Nb alloys with Nb concentrations up to 29 wt% was
      produced by cold-crucible casting, followed by homogenization treatment and water
      quenching. Despite the large amount of literature available concerning the
      thermal stability and ageing behavior of Ti-Nb alloys, only few studies were
      performed dealing with the isochronal transformation behavior of initially
      martensitic Ti-Nb alloys. In this work, the formation of martensites (alpha' and
      alpha") and their stability under different thermal processing conditions were
      investigated by a combination of x-ray diffraction, differential scanning
      calorimetry, dilatometry and electron microscopy. The effect of Nb additions on
      the structural competition in correlation with stable and metastable phase
      diagrams was also studied. Alloys with 24 wt% Nb or less undergo a [Formula: see
      text] transformation sequence on heating from room temperature to 1155 K. In
      alloys containing >24 wt% Nb alpha" martensitically reverts back to beta0, which
      is highly unstable against chemical demixing by formation of isothermal omegaiso.
      During slow cooling from the single phase beta domain alpha precipitates and only
      very limited amounts of alpha" martensite form.

PMID- 27877612
TI  - Material design of plasma-enhanced chemical vapour deposition SiCH films for low
      k cap layers in the further scaling of ultra-large-scale integrated devices-Cu
      interconnects.
AB  - Cap layers for Cu interconnects in ultra-large-scale integrated devices (ULSIs),
      with a low dielectric constant (k-value) and strong barrier properties against Cu
      and moisture diffusion, are required for the future further scaling of ULSIs.
      There is a trade-off, however, between reducing the k-value and maintaining
      strong barrier properties. Using quantum mechanical simulations and other
      theoretical computations, we have designed ideal dielectrics: SiCH films with Si
      C2H4-Si networks. Such films were estimated to have low porosity and low k; thus
      they are the key to realizing a cap layer with a low k and strong barrier
      properties against diffusion. For fabricating these ideal SiCH films, we designed
      four novel precursors: isobutyl trimethylsilane, diisobutyl dimethylsilane, 1, 1
      divinylsilacyclopentane and 5-silaspiro [4,4] noname, based on quantum chemical
      calculations, because such fabrication is difficult by controlling only the
      process conditions in plasma-enhanced chemical vapor deposition (PECVD) using
      conventional precursors. We demonstrated that SiCH films prepared using these
      newly designed precursors had large amounts of Si-C2H4-Si networks and strong
      barrier properties. The pore structure of these films was then analyzed by
      positron annihilation spectroscopy, revealing that these SiCH films actually had
      low porosity, as we designed. These results validate our material and precursor
      design concepts for developing a PECVD process capable of fabricating a low-k cap
      layer.

PMID- 27877613
TI  - Functionalization of polydimethylsiloxane membranes to be used in the production
      of voice prostheses.
AB  - The voice is produced by the vibration of vocal cords which are located in the
      larynx. Therefore, one of the major consequences for patients subjected to
      laryngectomy is losing their voice. In these cases, a synthetic one-way valve set
      (voice prosthesis) can be implanted in order to allow restoration of speech. Most
      voice prostheses are produced with silicone-based materials such as
      polydimethylsiloxane (PDMS). This material has excellent properties, such as
      optical transparency, chemical and biological inertness, non-toxicity,
      permeability to gases and excellent mechanical resistance that are fundamental
      for its application in the biomedical field. However, PDMS is very hydrophobic
      and this property causes protein adsorption which is followed by microbial
      adhesion and biofilm formation. To overcome these problems, surface modification
      of materials has been proposed in this study. A commercial silicone elastomer,
      SylgardTM 184 was used to prepare membranes whose surface was modified by
      grafting 2-hydroxyethylmethacrylate and methacrylic acid by low-pressure plasma
      treatment. The hydrophilicity, hydrophobic recovery and surface energy of the
      produced materials were determined. Furthermore, the cytotoxicity and
      antibacterial activity of the materials were also assessed. The results obtained
      revealed that the PDMS surface modification performed did not affect the
      material's biocompatibility, but decreased their hydrophobic character and
      bacterial adhesion and growth on its surface.

PMID- 27877614
TI  - Toughened and machinable glass matrix composites reinforced with graphene and
      graphene-oxide nano platelets.
AB  - The processing conditions for preparing well dispersed silica-graphene
      nanoplatelets and silica-graphene oxide nanoplatelets (GONP) composites were
      optimized using powder and colloidal processing routes. Fully dense silica-GONP
      composites with up to 2.5 vol% loading were consolidated using spark plasma
      sintering. The GONP aligned perpendicularly to the applied pressure during
      sintering. The fracture toughness of the composites increased linearly with
      increasing concentration of GONP and reached a value of ~0.9 MPa m1/2 for 2.5
      vol% loading. Various toughening mechanisms including GONP necking, GONP pull
      out, crack bridging, crack deflection and crack branching were observed. GONP
      decreased the hardness and brittleness index (BI) of the composites by ~30 and
      ~50% respectively. The decrease in BI makes silica-GONP composites machinable
      compared to pure silica. When compared to silica-Carbon nanotube composites,
      silica-GONP composites show better process-ability and enhanced mechanical
      properties.

PMID- 27877615
TI  - Growth and characterizations of Ba2Ti2Fe2As4O single crystals.
AB  - Single crystals of a new iron-based superconductor Ba2Ti2Fe2As4O have been grown
      successfully via a Ba2As3-flux method in a sealed evacuated quartz tube. Bulk
      superconductivity with Tc ~ 21.5 K was demonstrated in resistivity and magnetic
      susceptibility measurements after the as-grown crystals were annealed at 500 
      degrees C in vacuum for a week. X-ray diffraction patterns confirm that the
      annealed and the as-grown crystals possess the identical crystallographic
      structure of Ba2Ti2Fe2As4O. Energy-dispersive x-ray spectra indicate that partial
      Ti/Fe substitution exists in the [Fe2As2] layers and the annealing process
      redistributes the Ti within the Fe-plane. The ordered Fe-plane stabilized by
      annealing exhibits superconductivity with magnetic vortex pinned by Ti.

PMID- 27877616
TI  - Preparation and characterization of multifunctional magnetic mesoporous calcium
      silicate materials.
AB  - We have prepared multifunctional magnetic mesoporous Fe-CaSiO3 materials using
      triblock copolymer (P123) as a structure-directing agent. The effects of Fe
      substitution on the mesoporous structure, in vitro bioactivity, magnetic heating
      ability and drug delivery property of mesoporous CaSiO3 materials were
      investigated. Mesoporous Fe-CaSiO3 materials had similar mesoporous channels (5-6
      nm) with different Fe substitution. When 5 and 10% Fe were substituted for Ca in
      mesoporous CaSiO3 materials, mesoporous Fe-CaSiO3 materials still showed good
      apatite-formation ability and had no cytotoxic effect on osteoblast-like MC3T3-E1
      cells evaluated by the elution cell culture assay. On the other hand, mesoporous
      Fe-CaSiO3 materials could generate heat to raise the temperature of the
      surrounding environment in an alternating magnetic field due to their
      superparamagnetic property. When we use gentamicin (GS) as a model drug,
      mesoporous Fe-CaSiO3 materials release GS in a sustained manner. Therefore,
      magnetic mesoporous Fe-CaSiO3 materials would be a promising multifunctional
      platform with bone regeneration, local drug delivery and magnetic hyperthermia.

PMID- 27877617
TI  - The strengthening mechanism of a nickel-based alloy after laser shock processing
      at high temperatures.
AB  - We investigated the strengthening mechanism of laser shock processing (LSP) at
      high temperatures in the K417 nickel-based alloy. Using a laser-induced shock
      wave, residual compressive stresses and nanocrystals with a length of 30-200 nm
      and a thickness of 1 MUm are produced on the surface of the nickel-based alloy
      K417. When the K417 alloy is subjected to heat treatment at 900  degrees C after
      LSP, most of the residual compressive stress relaxes while the microhardness
      retains good thermal stability; the nanocrystalline surface has not obviously
      grown after the 900  degrees C per 10 h heat treatment, which shows a
      comparatively good thermal stability. There are several reasons for the good
      thermal stability of the nanocrystalline surface, such as the low value of cold
      hardening of LSP, extreme high-density defects and the grain boundary pinning of
      an impure element. The results of the vibration fatigue experiments show that the
      fatigue strength of K417 alloy is enhanced and improved from 110 to 285 MPa after
      LSP. After the 900  degrees C per 10 h heat treatment, the fatigue strength is
      225 MPa; the heat treatment has not significantly reduced the reinforcement
      effect. The feature of the LSP strengthening mechanism of nickel-based alloy at a
      high temperature is the co-working effect of the nanocrystalline surface and the
      residual compressive stress after thermal relaxation.

PMID- 27877618
TI  - Tunable and highly reproducible surface-enhanced Raman scattering substrates made
      from large-scale nanoparticle arrays based on periodically poled LiNbO3
      templates.
AB  - This work describes novel surface-enhanced Raman scattering (SERS) substrates
      based on ferroelectric periodically poled LiNbO3 templates. The templates
      comprise silver nanoparticles (AgNPs), the size and position of which are
      tailored by ferroelectric lithography. The substrate has uniform and large
      sampling areas that show SERS effective with excellent signal reproducibility,
      for which the fabrication protocol is advantageous in its simplicity. We
      demonstrate ferroelectric-based SERS substrates with particle sizes ranging from
      30 to 70 nm and present tunable SERS effect from Raman active 4-mercaptopyridine
      molecules attached to AgNPs when excited by a laser source at 514 nm.

PMID- 27877619
TI  - Local analysis of Eu2+ emission in CaAlSiN3.
AB  - We have investigated the local luminescence properties of Eu-doped CaAlSiN3 by
      using low-energy electron beam (e-beam) techniques. The particles yield broad
      emission centered at 655 nm with a shoulder at higher wavelength under light
      excitation, and a broad band around 643 nm with a tail at 540 nm under e-beam
      excitation. Using cathodoluminescence (CL) in a scanning electron microscope
      (SEM), we have observed small and large particles, which, although with different
      compositions, exhibit Eu2+-related emissions at 645 and 635 nm, respectively.
      Local CL measurements reveal that the Eu2+ emission may actually consist of
      several bands. In addition to the red broad band, regularly spaced sharp peaks
      have been occasionally observed. These luminescence variations may originate from
      a variation in the composition inside CaAlSiN3.

PMID- 27877620
TI  - Controlled processing of (Gd,Ln)2O3:Eu (Ln = Y, Lu) red phosphor particles and
      compositional effects on photoluminescence.
AB  - Synthesis of (Gd0.95-x Ln x Eu0.05)2O3 (Ln = Y and Lu, x = 0-0.95) powders via
      ammonium hydrogen carbonate (AHC) precipitation has been systematically studied.
      The best synthesis parameters are found to be an AHC/total cation molar ratio of
      4.5 and an ageing time of 3 h. The effects of Y3+ and Lu3+ substitution for Gd3+,
      on the nucleation kinetics of the precursors and structural features and optical
      properties of the oxides, have been investigated. The results show that (i)
      different nucleation kinetics exist in the Gd-Y-Eu and Gd-Lu-Eu ternary systems,
      which lead to various morphologies and particle sizes of the precipitated
      precursors. The (Gd,Y)2O3:Eu precursors display spherical particle morphologies
      and the particle sizes increase along with more Y3+ addition. The (Gd,Lu)2O3:Eu
      precursors, on the other hand, are hollow spheres and the particle sizes increase
      with increasing Lu3+ incorporation, (ii) the resultant oxide powders are
      ultrafine, narrow in size distribution, well dispersed and rounded in particle
      shape, (iii) lattice parameters of the two kinds of oxide solid solutions
      linearly decrease at a higher Y3+ or Lu3+ content. Their theoretical densities
      linearly decrease with increasing Y3+ incorporation, but increase along with more
      Lu3+ addition and (iv) the two kinds of phosphors exhibit typical red emissions
      at ~613 nm and their charge-transfer bands blue shift at a higher Y3+ or Lu3+
      content. Photoluminescence/photoluminescence excitation intensities and external
      quantum efficiency are found to decrease with increasing value of x, and the
      fluorescence lifetime mainly depends on the specific surface areas of the
      powders.

PMID- 27877622
TI  - Effect of zinc addition and vacuum annealing time on the properties of spin
      coated low-cost transparent conducting 1 at% Ga-ZnO thin films.
AB  - Pure and 1 at% gallium (Ga)-doped zinc oxide (ZnO) thin films have been prepared
      with a low-cost spin coating technique on quartz substrates and annealed at 500 
      degrees C in vacuum ~10-3 mbar to create anion vacancies and generate charge
      carriers for photovoltaic application. Also, 0.5-1.5 at% extra zinc species were
      added in the precursor sol to investigate changes in film growth, morphology,
      optical absorption, electrical properties and photoluminescence. It is shown that
      1 at% Ga-ZnO thin films with 0.5 at% extra zinc content after vacuum annealing
      for 60 min correspond to wurtzite-type hexagonal structure with (0001) preferred
      orientation, electrical resistivity of ~9 * 10-3 Omega cm and optical
      transparency of ~65-90% in the visible range. Evidence has been advanced for the
      presence of defect levels within bandgap such as zinc vacancy (VZn), zinc
      interstitial (Zni), oxygen vacancy (Vo) and oxygen interstitial (Oi). Further,
      variation in ZnO optical bandgap occurring with Ga doping and insertion of
      additional zinc species has been explained by invoking two competing phenomena,
      namely bandgap widening and renormalization, usually observed in semiconductors
      with increasing carrier concentration.

PMID- 27877621
TI  - Tuning the mechanical properties of glass fiber-reinforced bismaleimide-triazine
      resin composites by constructing a flexible bridge at the interface.
AB  - We demonstrate a new method that can simultaneously improve the strength and
      toughness of the glass fiber-reinforced bismaleimide-triazine (BT) resin
      composites by using polyethylene glycol (PEG) to construct a flexible bridge at
      the interface. The mechanical properties, including the elongation, ultimate
      tensile stress, Young's modulus, toughness and dynamical mechanical properties
      were studied as a function of the length of PEG molecular chain. It was found
      that the PEG molecule acts as a bridge to link BT resin and glass fiber through
      covalent and non-covalent bondings, respectively, resulting in improved
      interfacial bonding. The incorporation of PEG produces an increase in elongation,
      ultimate tensile stress and toughness. The Young's modulus and Tg were slightly
      reduced when the length of the PEG molecular chain was high. The elongation of
      the PEG-modified glass fiber-reinforced composites containing 5 wt% PEG-8000
      increased by 67.1%, the ultimate tensile stress by 17.9% and the toughness by
      78.2% compared to the unmodified one. This approach provides an efficient way to
      develop substrate material with improved strength and toughness for integrated
      circuit packaging applications.

PMID- 27877623
TI  - Micropatterned co-culture of hepatocyte spheroids layered on non-parenchymal
      cells to understand heterotypic cellular interactions.
AB  - Microfabrication and micropatterning techniques in tissue engineering offer great
      potential for creating and controlling cellular microenvironments including cell
      matrix interactions, soluble stimuli and cell-cell interactions. Here, we present
      a novel approach to generate layered patterning of hepatocyte spheroids on
      micropatterned non-parenchymal feeder cells using microfabricated poly(ethylene
      glycol) (PEG) hydrogels. Micropatterned PEG-hydrogel-treated substrates with two
      dimensional arrays of gelatin circular domains (phi = 100 MUm) were prepared by
      photolithographic method. Only on the critical structure of PEG hydrogel with
      perfect protein rejection, hepatocytes were co-cultured with non-parenchymal
      cells to be led to enhanced hepatocyte functions. Then, we investigated the
      mechanism of the functional enhancement in co-culture with respect to the
      contributions of soluble factors and direct cell-cell interactions. In
      particular, to elucidate the influence of soluble factors on hepatocyte function,
      hepatocyte spheroids underlaid with fibroblasts (NIH/3T3 mouse fibroblasts) or
      endothelial cells (BAECs: bovine aortic endothelial cells) were compared with
      physically separated co-culture of hepatocyte monospheroids with NIH3T3 or BAEC
      using trans-well culture systems. Our results suggested that direct heterotypic
      cell-to-cell contact and soluble factors, both of these between hepatocytes and
      fibroblasts, significantly enhanced hepatocyte functions. In contrast, direct
      heterotypic cell-to-cell contact between hepatocytes and endothelial cells only
      contributed to enhance hepatocyte functions. This patterning technique can be a
      useful experimental tool for applications in basic science, drug screening and
      tissue engineering, as well as in the design of artificial liver devices.

PMID- 27877626
TI  - Particle processing technology.

PMID- 27877625
TI  - MoO x thin films deposited by magnetron sputtering as an anode for aqueous micro
      supercapacitors.
AB  - In order to examine the potential application of non-stoichiometric molybdenum
      oxide as anode materials for aqueous micro-supercapacitors, conductive MoO x
      films (2 ? x ? 2.3) deposited via RF magnetron sputtering at different
      temperatures were systematically studied for composition, structure and
      electrochemical properties in an aqueous solution of Li2SO4. The MoO x (x ~ 2.3)
      film deposited at 150  degrees C exhibited a higher areal capacitance (31 mF cm-2
      measured at 5 mV s-1), best rate capability and excellent stability at potentials
      below -0.1 V versus saturated calomel electrode, compared to the films deposited
      at room temperature and at higher temperatures. These superior properties were
      attributed to the multi-valence composition and mixed-phase microstructure, i.e.,
      the coexistence of MoO2 nanocrystals and amorphous MoO x (2.3 < x ? 3). A
      mechanism combining Mo(IV) oxidation/reduction on the hydrated MoO2 grain
      surfaces and cation intercalation/extrusion is proposed to illustrate the pseudo
      capacitive process.

PMID- 27877624
TI  - Concurrent zero-dimensional and one-dimensional biomineralization of gold from a
      solution of Au3+ and bovine serum albumin.
AB  - A technique was developed for preparing a novel material that consists of gold
      nanoparticles trapped within a fiber of unfolded proteins. These fibers are made
      in an aqueous solution that contains HAuCl4 and the protein, bovine serum albumin
      (BSA). By changing the ratio of gold to BSA in solution, two different types of
      outcomes are observed. At lower gold to BSA ratios (30-120), a purple solution
      results after heating the mixture at 80  degrees C for 4 h. At higher gold to BSA
      ratios (130-170), a clear solution containing purple fibers results after heating
      the mixture at 80  degrees C for 4 h. UV-Vis spectroscopy and light scattering
      techniques show growth in nanocolloid size as gold to BSA ratio rises above 100.
      Data indicate that, for the higher gold to BSA ratios, the gold is sequestered
      within the solid material. The material mass, visible by eye, appears to be an
      aggregation of smaller individual fibers. Scanning electron microscopy and
      transmission electron microscopy indicate that these fibers are primarily one
      dimensional aggregates, which can display some branching, and can be as narrow as
      400 nm in size. The likely mechanism for the synthesis of the novel material is
      discussed.

PMID- 27877627
TI  - NIMS and Empa announce STAM collaboration.

PMID- 27877629
TI  - Microstructure and high-temperature strength of textured and non-textured ZrB2
      ceramics.
AB  - Zirconium diboride (ZrB2) ceramic possesses a unique combination of nice
      mechanical performance, high melting point (> 3000  degrees C) and great high
      temperature oxidation resistance (up to 1600  degrees C), which makes it a
      promising material system for ever-increasing ultra-high temperature (UHT)
      applications. However, ZrB2 suffers from poor mechanical performance at UHTs,
      which could strongly limit its applications at UHT. Here, we successfully
      demonstrate that texturing is an effective strategy to greatly enhance the
      flexural strength of monolithic ZrB2, reaching a high value of 810 +/- 60 MPa at
      1600  degrees C when loaded in c-axis direction. We thoroughly discuss the
      strengthening mechanism by in-depth microstructural observations and analysis.
      Our discovery has technological and scientific implications for other UHT ceramic
      systems, especially those using ZrB2 as a matrix.

PMID- 27877628
TI  - Mechanically reliable thermoelectric (TE) nanocomposites by dispersing and
      embedding TE-nanostructures inside a tetragonal ZrO2 matrix: the concept and
      experimental demonstration in graphene oxide-3YSZ system.
AB  - Novel low-dimensional thermoelectric (TE) materials suffer from poor mechanical
      reliability, which limits their applications, especially in mechanically harsh
      environments. Here, we propose a new concept, in which the novel, abundant,
      thermally stable TE-nanostructures are dispersed and then intimately embedded
      inside a protective, mechanically reliable tetragonal ZrO2 (TZP) ceramic matrix
      with a low thermal conductivity. We also demonstrate an experimental proof-of
      principle verification of our concept in reduced-graphene oxide (GO)-3 mol% Y2O3
      ZrO2 (3YSZ or 3Y-TZP) nanocomposite system. TE characterizations suggest that our
      protective TZP matrix does not degrade the intrinsic TE property of the reduced
      GO network. These preliminary results are promising and encouraging to start
      research on similar TZP-matrix TE-nanocomposites, which contain more effective TE
      nanostructures with larger intrinsic power factors. In this regard, we propose a
      scalable approach for fabrication of similar dense TE-nanocomposites composed of
      other one-dimensional and/or two-dimensional TE-nanostructures, which involves an
      aqueous colloidal approach and a subsequent spark plasma sintering. These new TZP
      matrix TE-nanocomposites could be used for sustainable clean power generation,
      especially in mechanically harsh environments with thermal/mechanical shocks and
      vibrations, where energy availability, reliability and durability are more
      important than the energy efficiency. Considering the excellent biocompatibility
      of TZP matrix, they could even be used inside the body to power implanted medical
      devices.

PMID- 27877630
TI  - Tens of micron-sized unilamellar nanosheets of Y/Eu layered rare-earth hydroxide:
      efficient exfoliation via fast anion exchange and their self-assembly into
      oriented oxide film with enhanced photoluminescence.
AB  - Layered rare-earth hydroxide (LRH) crystals of (Y0.95Eu0.05)2(OH)5NO3.nH2O with a
      lateral size of ~ 300 MUm and a thickness of ~ 9 MUm have been synthesized via a
      hydrothermal reaction of mixed nitrate solutions in the presence of mineralizer
      NH4NO3 at 200  degrees C for 24 h. LRH exhibits the ability to undergo
      intercalation and anion exchange with DS- (C12H25OSO3-) via hydrothermal
      treatment. Compared with traditional anion exchange at room temperature,
      hydrothermal processing not only shortens the anion exchange time from 720 to 24
      h but also increases the basal spacing. The arrangements of DS- in the interlayer
      of LRH are significantly affected by the DS- concentration and reaction
      temperature, and the basal spacing of the LRH-DS sample in the crystal edge is
      assumed to be larger than that in the crystal center. A higher DS- concentration
      and reaction temperature both induce more intercalation of DS- anions into the
      interlayer gallery, thus yielding a larger basal spacing. Unilamellar nanosheets
      with a lateral size of ?60 MUm and a thickness of ~ 1.6 nm can be obtained by
      delaminating LRH-DS in formamide. The resultant unilamellar nanosheets are single
      crystalline. Transparent (Y0.95Eu0.05)2O3 phosphor films with a uniform [111]
      orientation and a layer thickness of ~ 90 nm were constructed with the nanosheets
      as building blocks via spin-coating, followed by proper annealing. The oriented
      oxide film exhibits a strong red emission at 614 nm (the 5D0-7F2 transition of
      Eu3+), whose intensity is ~ 2 times that of the powder form owing to the
      significant exposure of the (222) facets.

PMID- 27877631
TI  - Facile and green synthesis of (La0.95Eu0.05)2O2S red phosphors with sulfate-ion
      pillared layered hydroxides as a new type of precursor: controlled hydrothermal
      processing, phase evolution and photoluminescence.
AB  - This study presents a facile and green route for the synthesis of
      (La0.95Eu0.05)2O2S red phosphors of controllable morphologies, with the sulfate
      type layered hydroxides of Ln2(OH)4SO4.2H2O (Ln = La and Eu) as a new type of
      precursor. The technique takes advantage of the fact that the precursor has had
      the exact Ln:S molar ratio of the targeted phosphor, thus saving the hazardous
      sulfurization reagents indispensable to traditional synthesis. Controlled
      hydrothermal processing at 120  degrees C yielded phase-pure Ln2(OH)4SO4.2H2O
      crystallites in the form of either nanoplates or microprisms, which can both be
      converted into Ln2O2S phosphor via a Ln2O2SO4 intermediate upon annealing in
      flowing H2 at a minimum temperature of ~ 700  degrees C. The nanoplates collapse
      into relatively rounded Ln2O2S particles while the microprisms retain well their
      initial morphologies at 1 200  degrees C, thus yielding two types of red
      phosphors. Photoluminescence excitation (PLE) studies found two distinct charge
      transfer (CT) excitation bands of O2- -> Eu3+ at ~ 270 nm and S2- -> Eu3+ at ~
      340 nm for the Ln2O2S phosphors, with the latter being stronger and both
      significantly stronger than the intrinsic intra-f transitions of Eu3+. The two
      types of phosphors share high similarities in the positions of PLE/PL
      (photoluminescence) bands and both show the strongest red emission at 627 nm (5D0
      -> 7F2 transition of Eu3+) under S2- -> Eu3+ CT excitation at 340 nm. The PLE/PL
      intensities show clear dependence on particle morphology and calcination
      temperature, which were investigated in detail. Fluorescence decay analysis
      reveals that the 627 nm red emission has a lifetime of ~ 0.5 ms for both types of
      the phosphors.

PMID- 27877632
TI  - Luminescent metal nanoclusters: controlled synthesis and functional applications.
AB  - Luminescent metal nanoclusters that consist of only several, to tens of, metal
      atoms and which possess sizes comparable to the Fermi wavelength of electrons
      have recently attracted significant attention. This new class of luminescent
      materials not only provides the missing link between atomic and nanoparticle
      behaviors in metals but also they present abundant novel information for the
      development of new applicable material systems to meet urgent needs in many areas
      (such as ultrasensitive sensors for heavy metals, bioimaging, as well as
      information technology) mainly because of their attractive characteristics,
      including ultra-small size, good dispersibility, excellent biocompatibility and
      photostability. In this review, we summarize recent advances in the controlled
      synthesis and application of luminescent metal nanoclusters, with a particular
      emphasis on Pt, Mo, Bi and alloy clusters. We also speculate on their future and
      discuss potential developments for their use in sensors, bioimaging and energy
      harvesting and conversion.

PMID- 27877633
TI  - Co(OH)2 nanosheet-decorated graphene-CNT composite for supercapacitors of high
      energy density.
AB  - A composite of graphene and carbon nanotubes has been synthesized and
      characterized for application as supercapacitor electrodes. By coating the
      nanostructured active material of Co(OH)2 onto one electrode, the asymmetric
      supercapacitor has exhibited a high specific capacitance of 310 F g-1, energy
      density of 172 Wh kg-1 and maximum power density of 198 kW kg-1 in ionic liquid
      electrolyte EMI-TFSI.

PMID- 27877634
TI  - Colloidal silicon quantum dots: synthesis and luminescence tuning from the near
      UV to the near-IR range.
AB  - This review describes a series of representative synthesis processes, which have
      been developed in the last two decades to prepare silicon quantum dots (QDs). The
      methods include both top-down and bottom-up approaches, and their methodological
      advantages and disadvantages are presented. Considerable efforts in surface
      functionalization of QDs have categorized it into (i) a two-step process and (ii)
      in situ surface derivatization. Photophysical properties of QDs are summarized to
      highlight the continuous tuning of photoluminescence color from the near-UV
      through visible to the near-IR range. The emission features strongly depend on
      the silicon nanostructures including QD surface configurations. Possible
      mechanisms of photoluminescence have been summarized to ascertain the future
      challenges toward industrial use of silicon-based light emitters.

PMID- 27877635
TI  - The effect of the interlayer element on the exfoliation of layered Mo2AC (A = Al,
      Si, P, Ga, Ge, As or In) MAX phases into two-dimensional Mo2C nanosheets.
AB  - The experimental exfoliation of layered, ternary transition-metal carbide and
      nitride compounds, known as MAX phases, into two-dimensional (2D) nanosheets, is
      a great development in the synthesis of novel low-dimensional inorganic systems.
      Among the MAX phases, Mo-containing ones might be considered as the source for
      obtaining Mo2C nanosheets with potentially unique properties, if they could be
      exfoliated. Here, by using a set of first-principles calculations, we discuss the
      effect of the interlayer 'A' element on the exfoliation of Mo2AC (A = Al, Si, P,
      Ga, Ge, As or In) MAX phases into the 2D Mo2C nanosheets. Based on the calculated
      exfoliation energies and the elastic constants, we propose that Mo2InC with the
      lowest exfoliation energy and the highest elastic constant anisotropy between C11
      and C33 might be a suitable compound for exfoliation into 2D Mo2C nanosheets.

PMID- 27877636
TI  - Fabrication of alumina films with laminated structures by ac anodization.
AB  - Anodization techniques by alternating current (ac) are introduced in this review.
      By using ac anodization, laminated alumina films are fabricated. Different types
      of alumina films consisting of 50-200 nm layers were obtained by varying both the
      ac power supply and the electrolyte. The total film thickness increased with an
      increase in the total charge transferred. The thickness of the individual layers
      increased with the ac voltage; however, the anodization time had little effect on
      the film thickness. The laminated alumina films resembled the nacre structure of
      shells, and the different morphologies exhibited by bivalves and spiral shells
      could be replicated by controlling the rate of increase of the applied
      potentials.

PMID- 27877638
TI  - Effects of surface coating on reducing friction and wear of orthopaedic implants.
AB  - Coatings such as diamond-like carbon (DLC) and titanium nitride (TiN) are
      employed in joint implants due to their excellent tribological properties.
      Recently, graphite-like carbon (GLC) and tantalum (Ta) have been proven to have
      good potential as coating as they possess mechanical properties similar to bones
      high hardness and high flexibility. The purpose of this systematic literature
      review is to summarize the coating techniques of these four materials in order to
      compare their mechanical properties and tribological outcomes. Eighteen studies
      published between January 2000 and February 2013 have met the inclusion criteria
      for this review. Details of their fabrication parameters, material and mechanical
      properties along with the tribological outcomes, such as friction and wear rate,
      were identified and are presented in a systematic way. Although experiment
      conditions varied, we conclude that Ta has the lowest wear rate compared to DLC,
      GLC and TiN because it has a lower wear rate with high contact pressure as well
      as higher hardness to elasticity ratio. However, a further tribology test is
      needed in an environment which replicates artificial joints to confirm the
      acceptability of these findings.

PMID- 27877639
TI  - Recent progress in GeSi electro-absorption modulators.
AB  - Electro-absorption from GeSi heterostructures is receiving growing attention as a
      high performance optical modulator for short distance optical interconnects. Ge
      incorporation with Si allows strong modulation mechanism using the Franz-Keldysh
      effect and the quantum-confined Stark effect from bulk and quantum well
      structures at telecommunication wavelengths. In this review, we discuss the
      current state of knowledge and the on-going challenges concerning the development
      of high performance GeSi electro-absorption modulators. We also provide feasible
      future prospects concerning this research topic.

PMID- 27877640
TI  - Magneto-optical non-reciprocal devices in silicon photonics.
AB  - Silicon waveguide optical non-reciprocal devices based on the magneto-optical
      effect are reviewed. The non-reciprocal phase shift caused by the first-order
      magneto-optical effect is effective in realizing optical non-reciprocal devices
      in silicon waveguide platforms. In a silicon-on-insulator waveguide, the low
      refractive index of the buried oxide layer enhances the magneto-optical phase
      shift, which reduces the device footprints. A surface activated direct bonding
      technique was developed to integrate a magneto-optical garnet crystal on the
      silicon waveguides. A silicon waveguide optical isolator based on the magneto
      optical phase shift was demonstrated with an optical isolation of 30 dB and
      insertion loss of 13 dB at a wavelength of 1548 nm. Furthermore, a four port
      optical circulator was demonstrated with maximum isolations of 15.3 and 9.3 dB in
      cross and bar ports, respectively, at a wavelength of 1531 nm.

PMID- 27877637
TI  - Creating biological nanomaterials using synthetic biology.
AB  - Synthetic biology is a new discipline that combines science and engineering
      approaches to precisely control biological networks. These signaling networks are
      especially important in fields such as biomedicine and biochemical engineering.
      Additionally, biological networks can also be critical to the production of
      naturally occurring biological nanomaterials, and as a result, synthetic biology
      holds tremendous potential in creating new materials. This review introduces the
      field of synthetic biology, discusses how biological systems naturally produce
      materials, and then presents examples and strategies for incorporating synthetic
      biology approaches in the development of new materials. In particular, strategies
      for using synthetic biology to produce both organic and inorganic nanomaterials
      are discussed. Ultimately, synthetic biology holds the potential to dramatically
      impact biological materials science with significant potential applications in
      medical systems.

PMID- 27877642
TI  - Activation of Al-Cu-Fe quasicrystalline surface: fabrication of a fine
      nanocomposite layer with high catalytic performance.
AB  - A fine layered nanocomposite with a total thickness of about 200 nm was formed on
      the surface of an Al63Cu25Fe12 quasicrystal (QC). The nanocomposite was found to
      exhibit high catalytic performance for steam reforming of methanol. The
      nanocomposite was formed by a self-assembly process, by leaching the Al-Cu-Fe QC
      using a 5 wt% Na2CO3 aqueous solution followed by calcination in air at 873 K.
      The quasiperiodic nature of theQC played an important role in the formation of
      such a structure. Its high catalytic activity originated from the presence of
      highly dispersed copper and iron species, which also suppressed the sintering of
      nanoparticles.

PMID- 27877641
TI  - Mid-infrared materials and devices on a Si platform for optical sensing.
AB  - In this article, we review our recent work on mid-infrared (mid-IR) photonic
      materials and devices fabricated on silicon for on-chip sensing applications.
      Pedestal waveguides based on silicon are demonstrated as broadband mid-IR
      sensors. Our low-loss mid-IR directional couplers demonstrated in SiN x
      waveguides are useful in differential sensing applications. Photonic crystal
      cavities and microdisk resonators based on chalcogenide glasses for high
      sensitivity are also demonstrated as effective mid-IR sensors. Polymer-based
      functionalization layers, to enhance the sensitivity and selectivity of our
      sensor devices, are also presented. We discuss the design of mid-IR chalcogenide
      waveguides integrated with polycrystalline PbTe detectors on a monolithic silicon
      platform for optical sensing, wherein the use of a low-index spacer layer enables
      the evanescent coupling of mid-IR light from the waveguides to the detector.
      Finally, we show the successful fabrication processing of our first prototype mid
      IR waveguide-integrated detectors.

PMID- 27877643
TI  - Interface effects and the evolution of ferromagnetism in La2/3Sr1/3MnO3 ultrathin
      films.
AB  - Pulse laser deposited La2/3Sr1/3MnO3 ultrathin films on SrTiO3 substrates were
      characterized by polar and longitudinal Kerr magneto-optical spectroscopy.
      Experimental data were confronted with theoretical simulations based on the
      transfer matrix formalism. An excellent agreement was achieved for a 10.7 nm
      thick film, while a distinction in the Kerr effect amplitudes was obtained for a
      5 nm thick film. This demonstrated the suppression of ferromagnetism due to the
      layer/substrate interface effects. A revised, depth-sensitive theoretical model
      with monolayer resolution described the experimental data well, and provided
      clear cross-section information about the evolution of ferromagnetism inside the
      film. It was found that the full restoration of the double-exchange mechanism,
      responsible for the ferromagnetic ordering in La2/3Sr1/3MnO3, occurs within the
      first nine monolayers of the film. Moreover, all the studied films exhibited
      magneto-optical properties similar to bulk crystals and thick films. This
      confirmed a fully developed perovskite structure down to 5 nm.

PMID- 27877644
TI  - A simple method for the quantification of molecular decorations on silica
      particles.
AB  - A simple, rapid quantitative approach to determining attachment density on silica
      nanoparticles has been demonstrated using attenuated total reflectance Fourier
      transform infrared spectroscopy and verified by thermogravimetric analysis. A
      very high attachment of approximately 5 attachments per nm2 has been achieved
      through photoinduced thiol-ene click reaction of 11-bromo-1-undecene with a thiol
      functionalized silica nanoparticle formed from mercaptopropyltrimethoxysilane as
      the sole precursor. Attachment density with concentration of alkene and reaction
      time is shown to be highly nonlinear and appears to be limited by accessability
      of thiols on the surface of the particle. This method opens the opportunity to
      form nanoparticles with controlled functionality including multifunctional
      particles, which have been produced in this work.

PMID- 27877645
TI  - Comparison of the cohesive and delamination fatigue properties of atomic-layer
      deposited alumina and titania ultrathin protective coatings deposited at 200 
      degrees C.
AB  - The fatigue properties of ultrathin protective coatings on silicon thin films
      were investigated. The cohesive and delamination fatigue properties of 22 nm
      thick atomic-layered-deposited (ALD) titania were characterized and compared to
      that of 25 nm-thick alumina. Both coatings were deposited at 200  degrees C. The
      fatigue rates are comparable at 30  degrees C, 50% relative humidity (RH) while
      they are one order of magnitude larger for alumina compared to titania at 80 
      degrees C, 90% RH. The improved fatigue performance is believed to be related to
      the improved stability of the ALD titania coating with water compared to ALD
      alumina, which may in part be related to the fact that ALD titania is
      crystalline, while ALD alumina is amorphous. Static fatigue crack nucleation and
      propagation was not observed. The underlying fatigue mechanism is different from
      previously documented mechanisms, such as stress corrosion cracking, and appears
      to result from the presence of compressive stresses and a rough coating-substrate
      interface.

PMID- 27877646
TI  - Studying nanostructure gradients in injection-molded
      polypropylene/montmorillonite composites by microbeam small-angle x-ray
      scattering.
AB  - The core-shell structure in oriented cylindrical rods of polypropylene (PP) and
      nanoclay composites (NCs) from PP and montmorillonite (MMT) is studied by
      microbeam small-angle x-ray scattering (SAXS). The structure of neat PP is almost
      homogeneous across the rod showing regular semicrystalline stacks. In the NCs the
      discrete SAXS of arranged crystalline PP domains is limited to a skin zone of 300
      MUm thickness. Even there only frozen-in primary lamellae are detected. The core
      of the NCs is dominated by diffuse scattering from crystalline domains placed at
      random. The SAXS of the MMT flakes exhibits a complex skin-core gradient. Both
      the direction of the symmetry axis and the apparent perfection of flake
      orientation are varying. Thus there is no local fiber symmetry, and the structure
      gradient cannot be reconstructed from a scan across the full rod. To overcome the
      problem the rods are machined. Scans across the residual webs are performed. For
      the first time webs have been carved out in two principal directions. Comparison
      of the corresponding two sets of SAXS patterns demonstrates the complexity of the
      MMT orientation. Close to the surface (< 1 mm) the flakes cling to the wall. The
      variation of the orientation distribution widths indicates the presence of both
      MMT flakes and grains. The grains have not been oriented in the flowing melt. An
      empirical equation is presented which describes the variation from skin to core
      of one component of the inclination angle of flake-shaped phyllosilicate filler
      particles.

PMID- 27877647
TI  - Transmission electron microscopy/electron energy loss spectroscopy measurements
      and ab initio calculation of local magnetic moments at nickel grain boundaries.
AB  - We have determined local magnetic moments at nickel grain boundaries using a
      transmission electron microscopy/electron energy loss spectroscopy method
      assuming that the magnetic moment of Ni atoms is a linear function of the L3/L2
      (white-line ratio) in the energy loss spectrum. The average magnetic moment
      measured in the grain interior was 0.55 MUB, which agrees well with the
      calculated magnetic moment of pure nickel (0.62 MUB). The local magnetic moments
      at the grain boundaries increased up to approximately 1.0 MUB as the mis
      orientation angle increased, and showed a maximum around 50 degrees . The
      respective enhancement of local magnetic moments at the Sigma5 (0.63 MUB) and
      random (0.90 MUB) grain boundaries in pure nickel was approximately 14 and 64% of
      the grain interior. In contrast, the average local magnetic moment at the (111)
      Sigma3 grain boundary was found to be 0.55 MUB and almost the same as that of the
      grain interior. These results are in good agreement with available ab initio
      calculations.

PMID- 27877648
TI  - Properties of anodic oxides grown on a hafnium-tantalum-titanium thin film
      library.
AB  - A ternary thin film combinatorial materials library of the valve metal system Hf
      Ta-Ti obtained by co-sputtering was studied. The microstructural and
      crystallographic analysis of the obtained compositions revealed a crystalline and
      textured surface, with the exception of compositions with Ta concentration above
      48 at.% which are amorphous and show a flat surface. Electrochemical anodization
      of the composition spread thin films was used for analysing the growth of the
      mixed surface oxides. Oxide formation factors, obtained from the potentiodynamic
      anodization curves, as well as the dielectric constants and electrical
      resistances, obtained from electrochemical impedance spectroscopy, were mapped
      along two dimensions of the library using a scanning droplet cell microscope. The
      semiconducting properties of the anodic oxides were mapped using Mott-Schottky
      analysis. The degree of oxide mixing was analysed qualitatively using x-ray
      photoelectron spectroscopy depth profiling. A quantitative analysis of the
      surface oxides was performed and correlated to the as-deposited metal thin film
      compositions. In the concurrent transport of the three metal cations during oxide
      growth a clear speed order of Ti > Hf > Ta was proven.

PMID- 27877649
TI  - Immobilization of carbon nanotubes on functionalized graphene film grown by
      chemical vapor deposition and characterization of the hybrid material.
AB  - We report the surface functionalization of graphene films grown by chemical vapor
      deposition and fabrication of a hybrid material combining multi-walled carbon
      nanotubes and graphene (CNT-G). Amine-terminated self-assembled monolayers were
      prepared on graphene by the UV-modification of oxidized groups introduced onto
      the film surface. Amine-termination led to effective interaction with
      functionalized CNTs to assemble a CNT-G hybrid through covalent bonding.
      Characterization clearly showed no defects of the graphene film after the
      immobilization reaction with CNT. In addition, the hybrid graphene material
      revealed a distinctive CNT-G structure and p-n type electrical properties. The
      introduction of functional groups on the graphene film surface and fabrication of
      CNT-G hybrids with the present technique could provide an efficient, novel route
      to device fabrication.

PMID- 27877650
TI  - Atomic force microscopy visualization of hard segment alignment in stretched
      polyurethane nanofibers prepared by electrospinning.
AB  - Molecular-level orientation within nanofibers has been attracting attention as a
      tool for controlling and designing highly functional nanofibers. In this study,
      we used atomic force microscopy to visualize the phase separation between soft
      and hard segments on a polyurethane (PU) nanofiber surface prepared by
      electrospinning. Furthermore, the stretched nanofibers prepared with a high-speed
      rotating collector were found to have a different phase distribution in the phase
      separated structure, with the hard segment domains aligned to the fiber axis. In
      contrast, unstretched PU nanofibers prepared without rotation were observed to
      have nonuniformly distributed segments. These results indicate that the
      application of an intense elongation force along the nanofiber axis with a
      rotating mandrel collector changed the distribution of segment alignments.

PMID- 27877651
TI  - Magnetovolume effects in manganese nitrides with antiperovskite structure.
AB  - Magnetostructural correlations in antiperovskite manganese nitrides were
      investigated systematically for stoichiometric and solid solution Mn3Cu1-x A x N
      (A = Co, Ni, Zn, Ga, Ge, Rh, Pd, Ag, In, Sn or Sb). This class of nitrides is
      attracting great attention because of their giant negative thermal expansion,
      which is achieved by doping Ge or Sn into the A site as a relaxant of the sharp
      volume contraction on heating (spontaneous volume magnetostriction omegas)
      because of the magnetovolume effects. The physical background of large omegas and
      mechanism of how the volume contraction becomes gradual with temperature are
      central concerns for the physics and applications of these nitrides. An entire
      dataset of thermal expansion, crystal structure and magnetization demonstrates
      that the cubic triangular antiferromagnetic state is crucial for large omegas.
      The intimate relationship between omegas and the magnetic structure is discussed
      in terms of geometrical frustration related to the Mn6N octahedron and magnetic
      stress concept. The results presented herein also show that omegas depends on the
      number of d electrons in the A atom, suggesting the important role of the d
      orbitals of the A atom. Not all the dopants in the A site, but the elements that
      disturb the cubic triangular antiferromagnetic state, are effective in broadening
      the volume change. This fact suggests that instability neighboring the phase
      boundary is related to the broadening. The relation between the gradual volume
      change and the local structure anomaly is suggested by recent microprobe studies.

PMID- 27877653
TI  - Focus on silicon photonics.

PMID- 27877652
TI  - Electric-field-induced phase transitions in co-doped Pb(Zr1-xTix)O3 at the
      morphotropic phase boundary.
AB  - The strain- and polarization-electric field behavior was characterized at room
      temperature for Pb0.98Ba0.01(Zr1-x Ti x )0.98Nb0.02O3, 0.40 ? x ? 0.60. The
      investigated compositions were located in the vicinity of the morphotropic phase
      boundary, giving insight into the influence of crystal structure on the
      hysteretic ferroelectric behavior. The remanent strain of particular compositions
      is shown to be larger than theoretically allowed by ferroelectric switching
      alone, indicating the presence of additional remanent strain mechanisms. A
      phenomenological free energy analysis was used to simulate the effect of an
      applied electric field on the initial equilibrium phase. It is shown that
      electric-field-induced phase transitions in polycrystalline ferroelectrics can
      account for the experimental observations. The experimental and simulation
      results are contrasted to neutron diffraction measurements performed on
      representative compositions in the virgin and remanent states.

PMID- 27877654
TI  - 5, 10-linked naphthodithiophenes as the building block for semiconducting
      polymers.
AB  - We present new semiconducting polymers incorporating naphtho[1, 2-b:5, 6-b']
      dithiophene (NDT3) and naphtho[2, 1-b:6, 5-b'] dithiophene (NDT4), which are
      linked at the naphthalene positions, in the polymer backbone. It is interesting
      that the trend in the ordering structure and thus charge transport properties are
      quite different from what were observed in the isomeric polymers where the NDT3
      and NDT4 cores are linked at the thiophene alpha-positions. In the thiophene
      linked NDT system, the NDT3-based polymer (PNDT3BT) gave the better ordering in
      thin films and thus the high charge carrier mobility compared to the NDT4-based
      polymer (PNDT4BT). In the meantime, in the naphthalene-linked NDT system, the
      NDT4-based polymer (PNDT4iBT) provided the superior properties. Considering that
      PNDT4iBT has relatively low highest occupied molecular orbital (HOMO) energy
      level (-5.2 eV) and moderately high mobilities in the order of 10-2 cm2 V-1 s-1,
      the NDT4 core, when linked at the naphthalene positions, can be a good building
      unit for the development of high-performance semiconducting polymers for both
      organic field-effect transistors and photovoltaic devices.

PMID- 27877655
TI  - Recent progress in photoactive organic field-effect transistors.
AB  - Recent progress in photoactive organic field-effect transistors (OFETs) is
      reviewed. Photoactive OFETs are divided into light-emitting (LE) and light
      receiving (LR) OFETs. In the first part, LE-OFETs are reviewed from the viewpoint
      of the evolution of device structures. Device performances have improved in the
      last decade with the evolution of device structures from single-layer unipolar to
      multi-layer ambipolar transistors. In the second part, various kinds of LR-OFETs
      are featured. These are categorized according to their functionalities:
      phototransistors, non-volatile optical memories, and photochromism-based
      transistors. For both, various device configurations are introduced: thin-film
      based transistors for practical applications, single-crystalline transistors to
      investigate fundamental physics, nanowires, multi-layers, and vertical
      transistors based on new concepts.

PMID- 27877657
TI  - Germanium epitaxy on silicon.
AB  - With the rapid development of on-chip optical interconnects and optical computing
      in the past decade, silicon-based integrated devices for monolithic and hybrid
      optoelectronic integration have attracted wide attention. Due to its narrow
      pseudo-direct gap behavior and compatibility with Si technology, epitaxial Ge-on
      Si has become a significant material for optoelectronic device applications. In
      this paper, we describe recent research progress on heteroepitaxy of Ge flat
      films and self-assembled Ge quantum dots on Si. For film growth, methods of
      strain modification and lattice mismatch relief are summarized, while for dot
      growth, key process parameters and their effects on the dot density, dot
      morphology and dot position are reviewed. The results indicate that epitaxial Ge
      on-Si materials will play a bigger role in silicon photonics.

PMID- 27877656
TI  - Patterning technology for solution-processed organic crystal field-effect
      transistors.
AB  - Organic field-effect transistors (OFETs) are fundamental building blocks for
      various state-of-the-art electronic devices. Solution-processed organic crystals
      are appreciable materials for these applications because they facilitate large
      scale, low-cost fabrication of devices with high performance. Patterning organic
      crystal transistors into well-defined geometric features is necessary to develop
      these crystals into practical semiconductors. This review provides an update on
      recentdevelopment in patterning technology for solution-processed organic
      crystals and their applications in field-effect transistors. Typical
      demonstrations are discussed and examined. In particular, our latest research
      progress on the spin-coating technique from mixture solutions is presented as a
      promising method to efficiently produce large organic semiconducting crystals on
      various substrates for high-performance OFETs. This solution-based process also
      has other excellent advantages, such as phase separation for self-assembled
      interfaces via one-step spin-coating, self-flattening of rough interfaces, and in
      situ purification that eliminates the impurity influences. Furthermore,
      recommendations for future perspectives are presented, and key issues for further
      development are discussed.

PMID- 27877658
TI  - Slow-light Mach-Zehnder modulators based on Si photonic crystals.
AB  - Mach-Zehnder optical modulators are the key devices for high-speed electrical-to
      optical conversion in Si photonics. Si rib waveguides with a p-n diode structure
      operated in the carrier depletion mode have mainly been developed as their phase
      shifters. Their length is usually longer than millimeters due to the limited
      change in the refractive index due to the carrier depletion in a Si p-n diode.
      This length is shorter than commercial LiNbO3 modulators, but still much shorter
      devices are desired for large-scale integration and for simplifying the high
      speed RF modulation. A promising solution is to use slow light in photonic
      crystal waveguides, which enhances the modulation efficiency in proportion to the
      group-velocity refractive index ng. In particular, dispersion-engineered slow
      light allows more than five-fold enhancement, maintaining a wide working spectrum
      as well as large temperature tolerance. The devices with a phase shifter length
      of around 100 MUm are fabricated by a standard process compatible with
      complementary metal-oxide semiconductors. The operation at 10 Gbps and higher
      speeds are obtained in the wavelength range of 16.9 nm and temperature range of
      105 K.

PMID- 27877659
TI  - High-performance silicon photonics technology for telecommunications
      applications.
AB  - By way of a brief review of Si photonics technology, we show that significant
      improvements in device performance are necessary for practical telecommunications
      applications. In order to improve device performance in Si photonics, we have
      developed a Si-Ge-silica monolithic integration platform, on which compact Si-Ge
      based modulators/detectors and silica-based high-performance wavelength filters
      are monolithically integrated. The platform features low-temperature silica film
      deposition, which cannot damage Si-Ge-based active devices. Using this platform,
      we have developed various integrated photonic devices for broadband
      telecommunications applications.

PMID- 27877660
TI  - Quasicrystal-reinforced Mg alloys.
AB  - The formation of the icosahedral phase (I-phase) as a secondary solidification
      phase in Mg-Zn-Y and Mg-Zn-Al base systems provides useful advantages in
      designing high performance wrought magnesium alloys. The strengthening in two
      phase composites (I-phase + alpha-Mg) can be explained by dispersion hardening
      due to the presence of I-phase particles and by the strong bonding property at
      the I-phase/matrix interface. The presence of an additional secondary
      solidification phase can further enhance formability and mechanical properties.
      In Mg-Zn-Y alloys, the co-presence of I and Ca2Mg6Zn3 phases by addition of Ca
      can significantly enhance formability, while in Mg-Zn-Al alloys, the co-presence
      of the I-phase and Mg2Sn phase leads to the enhancement of mechanical properties.
      Dynamic and static recrystallization are significantly accelerated by addition of
      Ca in Mg-Zn-Y alloy, resulting in much smaller grain size and more random
      texture. The high strength of Mg-Zn-Al-Sn alloys is attributed to the presence of
      finely distributed Mg2Sn and I-phase particles embedded in the alpha-Mg matrix.

PMID- 27877661
TI  - Complex metallic alloys as new materials for additive manufacturing.
AB  - Additive manufacturing processes allow freeform fabrication of the physical
      representation of a three-dimensional computer-aided design (CAD) data model.
      This area has been expanding rapidly over the last 20 years. It includes several
      techniques such as selective laser sintering and stereolithography. The range of
      materials used today is quite restricted while there is a real demand for
      manufacturing lighter functional parts or parts with improved functional
      properties. In this article, we summarize recent work performed in this field,
      introducing new composite materials containing complex metallic alloys. These are
      mainly Al-based quasicrystalline alloys whose properties differ from those of
      conventional alloys. The use of these materials allows us to produce light-weight
      parts consisting of either metal-matrix composites or of polymer-matrix
      composites with improved properties. Functional parts using these alloys are now
      commercialized.

PMID- 27877662
TI  - Modulation of human dermal microvascular endothelial cell and human gingival
      fibroblast behavior by micropatterned silica coating surfaces for zirconia dental
      implant applications.
AB  - Dental ceramic implants have shown superior esthetic behavior and the absence of
      induced allergic disorders when compared to titanium implants. Zirconia may
      become a potential candidate to be used as an alternative to titanium dental
      implants if surface modifications are introduced. In this work, bioactive
      micropatterned silica coatings were produced on zirconia substrates, using a
      combined methodology of sol-gel processing and soft lithography. The aim of the
      work was to compare the in vitro behavior of human gingival fibroblasts (HGFs)
      and human dermal microvascular endothelial cells (HDMECs) on three types of
      silica-coated zirconia surfaces: flat and micropatterned (with pillars and with
      parallel grooves). Our results showed that cells had a higher metabolic activity
      (HGF, HDMEC) and increased gene expression levels of fibroblast-specific protein
      1 (FSP-1) and collagen type I (COL I) on surfaces with pillars. Nevertheless,
      parallel grooved surfaces were able to guide cell growth. Even capillary tube
      like networks of HDMEC were oriented according to the surface geometry. Zirconia
      and silica with different topographies have shown to be blood compatible and
      silica coating reduced bacteria adhesion. All together, the results indicated
      that microstructured bioactive coating seems to be an efficient strategy to
      improve soft tissue integration on zirconia implants, protecting implants from
      peri-implant inflammation and improving long-term implant stabilization. This new
      approach of micropatterned silica coating on zirconia substrates can generate
      promising novel dental implants, with surfaces that provide physical cues to
      guide cells and enhance their behavior.

PMID- 27877664
TI  - Preparation and characterization of self-assembled percolative BaTiO3-CoFe2O4
      nanocomposites via magnetron co-sputtering.
AB  - BaTiO3-CoFe2O4 composite films were prepared on (100) SrTiO3 substrates by using
      a radio-frequency magnetron co-sputtering method at 750  degrees C. These films
      contained highly (001)-oriented crystalline phases of perovskite BaTiO3 and
      spinel CoFe2O4, which can form a self-assembled nanostructure with BaTiO3 well
      dispersed into CoFe2O4 under optimized sputtering conditions. A prominent
      dielectric percolation behavior was observed in the self-assembled nanocomposite.
      Compared with pure BaTiO3 films sputtered under similar conditions, the
      nanocomposite film showed higher dielectric constants and lower dielectric losses
      together with a dramatically suppressed frequency dispersion. This dielectric
      percolation phenomenon can be explained by the 'micro-capacitor' model, which was
      supported by measurement results of the electric polarization and leakage
      current.

PMID- 27877663
TI  - Nanoalloying and phase transformations during thermal treatment of physical
      mixtures of Pd and Cu nanoparticles.
AB  - Nanoscale alloying and phase transformations in physical mixtures of Pd and Cu
      ultrafine nanoparticles are investigated in real time with in situ synchrotron
      based x-ray diffraction complemented by ex situ high-resolution transmission
      electron microscopy. The combination of metal-support interaction and
      reactive/non-reactive environment was found to determine the thermal evolution
      and ultimate structure of this binary system. At 300  degrees C, the
      nanoparticles supported on silica and carbon black intermix to form a chemically
      ordered CsCl-type (B2) alloy phase. The B2 phase transforms into a disordered fcc
      alloy at higher temperature (> 450  degrees C). The alloy nanoparticles supported
      on silica and carbon black are homogeneous in volume, but evidence was found of
      Pd surface enrichment. In sharp contrast, when supported on alumina, the two
      metals segregated at 300  degrees C to produce almost pure fcc Cu and Pd phases.
      Upon further annealing of the mixture on alumina above 600  degrees C, the two
      metals interdiffused, forming two distinct disordered alloys of compositions 30%
      and 90% Pd. The annealing atmosphere also plays a major role in the structural
      evolution of these bimetallic nanoparticles. The nanoparticles annealed in
      forming gas are larger than the nanoparticles annealing in helium due to
      reduction of the surface oxides that promotes coalescence and sintering.

PMID- 27877665
TI  - Laser-vibrometric ultrasonic characterization of resonant modes and quality
      factors of Ge membranes.
AB  - The vibrations of a single-crystal germanium (Ge) membrane are studied in air and
      vacuum using laser vibrometry, in order to determine mechanical properties such
      as Q-factors, tensile stress, anisotropy, and robustness to shock. Resonance
      modes up to 3:2 are identified, giving a residual stress measurement of 0.22 GPa,
      consistent with the value obtained from x-ray relaxation studies. The membrane is
      found to be isotropic, with Q-factors ranging from around 40 at atmospheric
      pressure to over 3200 at [Formula: see text] mbar, significantly lower than those
      found in polycrystalline Ge micromechanical devices. The robustness to shock is
      explained through the high resonance mode frequencies and the dissipation
      mechanism into the substrate, which is a direct consequence of having a high
      quality film with low residual tensile stress, giving the potential for such
      films to be used in optoelectronic devices.

PMID- 27877666
TI  - Fabrication of flexible transparent conductive films from long double-walled
      carbon nanotubes.
AB  - The fabrication of flexible transparent conducting films (TCFs) is important for
      the development of the next-generation flexible devices. In this study, we used
      double-walled carbon nanotubes (DWCNTs) as the starting material and described a
      fabrication method of flexible TCFs. We have determined in a quantitative way
      that the key factors are the length and the dispersion states of the DWCNTs as
      well as the weight-ratios of dispersant polymer/DWCNTs. By controlling such
      factors, we have readily fabricated a flexible highly transparent (94%
      transmittance) and conductive (surface resistivity = 320 Omega sq-1) DWCNT film
      without adding any chemical doping that is often used to reduce the surface
      resistivity. By applying a wet coating, we have succeeded in the fabrication of
      large-scale conducting transparent DWCNT films based on the role-to-role method.

PMID- 27877667
TI  - High throughput production of nanocomposite SiO x powders by plasma spray
      physical vapor deposition for negative electrode of lithium ion batteries.
AB  - Nanocomposite Si/SiO x powders were produced by plasma spray physical vapor
      deposition (PS-PVD) at a material throughput of 480 g h-1. The powders are
      fundamentally an aggregate of primary ~20 nm particles, which are composed of a
      crystalline Si core and SiO x shell structure. This is made possible by complete
      evaporation of raw SiO powders and subsequent rapid condensation of high
      temperature SiO x vapors, followed by disproportionation reaction of nucleated
      SiO x nanoparticles. When CH4 was additionally introduced to the PS-PVD, the
      volume of the core Si increases while reducing potentially the SiO x shell
      thickness as a result of the enhanced SiO reduction, although an unfavorable SiC
      phase emerges when the C/Si molar ratio is greater than 1. As a result of the
      increased amount of Si active material and reduced source for irreversible
      capacity, half-cell batteries made of PS-PVD powders with C/Si = 0.25 have
      exhibited improved initial efficiency and maintenance of capacity as high as 1000
      mAh g-1 after 100 cycles at the same time.

PMID- 27877668
TI  - First-principles quantum molecular dynamics study of Ti x Zr1-x N(111)/SiN y
      heterostructures and comparison with experimental results.
AB  - The heterostructures of five monolayers B1-Ti x Zr1-x N(111), x = 1.0, 0.6, 0.4
      and 0.0 (where B1 is a NaCl-type structure) with one monolayer of a Si3N4-like
      Si2N3 interfacial layer were investigated by means of first-principles quantum
      molecular dynamics and a structure optimization procedure using the Quantum
      ESPRESSO code. Slabs consisting of stoichiometric TiN and ZrN and random, as well
      as segregated, B1-Ti x Zr1-x N(111) solutions were considered. The calculations
      of the B1-Ti x Zr1-x N solid solutions, as well as of the heterostructures,
      showed that the pseudo-binary TiN-ZrN system exhibits a miscibility gap. The
      segregated heterostructures in which Zr atoms surround the Si y N z interface
      were found to be the most stable. For the Zr-rich heterostructures, the total
      energy of the random solid solution was lower compared to that of the segregated
      one, whereas for the Ti-rich heterostructures the opposite tendency was observed.
      Hard and super hard Zr-Ti-Si-N coatings with thicknesses from 2.8 to 3.5 MUm were
      obtained using a vacuum arc source with high frequency stimulation. The samples
      were annealed in a vacuum and in air at 1200  degrees C. Experimental
      investigations of Zr-Ti-N, Zr-Ti-Si-N and Ti-Si-N coatings with different Zr, Ti
      and Si concentrations were carried out for comparison with results obtained from
      Ti x Zr 1-x N(111)/SiN y systems. During annealing, the hardness of the best
      series samples was increased from (39.6 +/- 1.4) to 53.6 GPa, which seemed to
      indicate that a spinodal segregation along grain interfaces was finished. A
      maximum hardness of 40.8 GPa before and 55 GPa after annealing in air at 500 
      degrees C was observed for coatings with a concentration of elements of Si? (7-8)
      at.%, Ti ? 22 at.% and Zr ? 70 at.%.

PMID- 27877669
TI  - Blue fluorescent OLED materials and their application for high-performance
      devices.
AB  - The authors applied two technologies to improve the efficiency of fluorescent
      blue organic light-emitting diodes (OLEDs). First, an efficiency-enhancement
      layer (EEL) was introduced to boost triplet-triplet fusion (TTF). Second, new
      blue dopants with a higher orientation factor in the emitting layer were
      developed. Consequently, the external quantum efficiency (EQE) was increased up
      to 11.5% with Commission Internationale de l'Eclairage (CIE) 1931 color
      coordinates of (0.138, 0.092). The reported results may lead to EQEs that exceed
      14% with fluorescent blue emitters.

PMID- 27877670
TI  - Donor-acceptor-structured 1,4-diazatriphenylene derivatives exhibiting thermally
      activated delayed fluorescence: design and synthesis, photophysical properties
      and OLED characteristics.
AB  - A new series of luminescent 1,4-diazatriphenylene (ATP) derivatives with various
      peripheral donor units, including phenoxazine, 9,9-dimethylacridane and 3
      (diphenylamino)carbazole, is synthesized and characterized as thermally activated
      delayed fluorescence (TADF) emitters. The influence of the donor substituents on
      the electronic and photophysical properties of the materials is investigated by
      theoretical calculations and experimental spectroscopic measurements. These ATP
      based molecules with donor-acceptor-donor (D-A-D) structures can reduce the
      singlet-triplet energy gap (0.04-0.26 eV) upon chemical modification of the ATP
      core, and thus exhibit obvious TADF characteristics in solution and doped thin
      films. As a demonstration of the potential of these materials, organic light
      emitting diodes containing the D-A-D-structured ATP derivatives as emitters are
      fabricated and tested. External electroluminescence quantum efficiencies above
      12% and 8% for green- and sky-blue-emitting devices, respectively, are achieved.

PMID- 27877671
TI  - Recent progress of high performance polymer OLED and OPV materials for organic
      printed electronics.
AB  - The development of organic printed electronics has been expanding to a variety of
      applications and is expected to bring innovations to our future life. Along with
      this trend, high performance organic materials with cost-efficient fabrication
      processes and specific features such as thin, light weight, bendable, and low
      power consumption are required. A variety of organic materials have been
      investigated in the development of this field. The basic guidelines for material
      design and the recent progress of polymer-based organic light-emitting diodes
      (OLEDs) and organic photovoltaic cells (OPVs) are reported.

PMID- 27877672
TI  - Deformation at ambient and high temperature of in situ Laves phases-ferrite
      composites.
AB  - The mechanical behavior of a Fe80Zr10Cr10 alloy has been studied at ambient and
      high temperature. This Fe80Zr10Cr10 alloy, whoose microstructure is formed by
      alternate lamellae of Laves phase and ferrite, constitutes a very simple example
      of an in situ CMA phase composite. The role of the Laves phase type was
      investigated in a previous study while the present work focuses on the influence
      of the microstructure length scale owing to a series of alloys cast at different
      cooling rates that display microstructures with Laves phase lamellae width
      ranging from ~50 nm to ~150 nm. Room temperature compression tests have revealed
      a very high strength (up to 2 GPa) combined with a very high ductility (up to
      35%). Both strength and ductility increase with reduction of the lamella width.
      High temperature compression tests have shown that a high strength (900 MPa) is
      maintained up to 873 K. Microstructural study of the deformed samples suggests
      that the confinement of dislocations in the ferrite lamellae is responsible for
      strengthening at both ambient and high temperature. The microstructure scale in
      addition to CMA phase structural features stands then as a key parameter for
      optimization of mechanical properties of CMA in situ composites.

PMID- 27877673
TI  - Surfaces of Al-based complex metallic alloys: atomic structure, thin film growth
      and reactivity.
AB  - We present a review on recent work performed on periodic complex metallic alloy
      (CMA) surfaces. The electronic and crystallographic structures of clean pseudo
      tenfold, pseudo-twofold, sixfold surfaces will be presented along with the recent
      findings on CMA of lower structural complexity, i.e. with a smaller unit cell.
      The use of CMA surfaces as templates for thin film growth and the formation of
      surface alloy will also be introduced. The reactivity of these complex surfaces
      and their impact in the field of heterogeneous catalysis will be discussed.
      Finally, common trends among these systems will be highlighted when possible and
      future challenges will be examined.

PMID- 27877674
TI  - Intermetallic compounds in heterogeneous catalysis-a quickly developing field.
AB  - The application of intermetallic compounds for understanding in heterogeneous
      catalysis developed in an excellent way during the last decade. This review
      provides an overview of concepts and developments revealing the potential of
      intermetallic compounds in fundamental as well as applied catalysis research.
      Intermetallic compounds may be considered as platform materials to address
      current and future catalytic challenges, e.g. in respect to the energy
      transition.

PMID- 27877675
TI  - Friction and solid-solid adhesion on complex metallic alloys.
AB  - The discovery in 1987 of stable quasicrystals in the Al-Cu-Fe system was soon
      exploited to patent specific coatings that showed reduced friction in ambient air
      against hard antagonists. Henceforth, it was possible to develop a number of
      applications, potential or commercially exploited to date, that will be alluded
      to in this topical review. A deeper understanding of the characteristics of
      complex metallic alloys (CMAs) may explain why material made of metals like Al,
      Cu and Fe offers reduced friction; low solid-solid adhesion came later. It is
      linked to the surface energy being significantly lower on those materials, in
      which translational symmetry has become a weak property, that is determined by
      the depth of the pseudo-gap at the Fermi energy. As a result, friction is
      anisotropic in CMAs that builds up according to the translation symmetry along
      one direction, but is aperiodic along the other two directions. A review is given
      in this article of the most salient data found along these lines during the past
      two decades or so.

PMID- 27877676
TI  - Photonic crystals, amorphous materials, and quasicrystals.
AB  - Photonic crystals consist of artificial periodic structures of dielectrics, which
      have attracted much attention because of their wide range of potential
      applications in the field of optics. We may also fabricate artificial amorphous
      or quasicrystalline structures of dielectrics, i.e. photonic amorphous materials
      or photonic quasicrystals. So far, both theoretical and experimental studies have
      been conducted to reveal the characteristic features of their optical properties,
      as compared with those of conventional photonic crystals. In this article, we
      review these studies and discuss various aspects of photonic amorphous materials
      and photonic quasicrystals, including photonic band gap formation, light
      propagation properties, and characteristic photonic states.

PMID- 27877677
TI  - High-rate and wide-area deposition of epitaxial Si films by mesoplasma chemical
      vapor deposition.
AB  - Homoepitaxial Si films have been deposited at a high rate of 200 nm s-1 over a
      wide area of 20 mm * 80 mm by cluster-assisted mesoplasma chemical vapor
      deposition (MPCVD) on a moving substrate. The obtained epitaxial Si films
      exhibited a uniform roughness of 0.1-0.3 nm (1 * 1 MUm2) and a Hall mobility of
      ~240 cm2 V-1 s-1. The results suggested that under the MPCVD the deposition
      precursors formed at the plasma edge could be small enough not to influence
      either epitaxial film structure or the film quality provided the substrate
      temperature is maintained above 500  degrees C.

PMID- 27877678
TI  - Development of nitroxide radicals-containing polymer for scavenging reactive
      oxygen species from cigarette smoke.
AB  - We developed a nitroxide radicals-containing polymer (NRP), which is composed of
      poly(4-methylstyrene) possessing nitroxide radicals as a side chain via amine
      linkage, to scavenge reactive oxygen species (ROS) from cigarette smoke. In this
      study, the NRP was coated onto cigarette filters and its ROS-scavenging activity
      from streaming cigarette smoke was evaluated. The intensity of electron spin
      resonance signals of the NRP in the filter decreased after exposure to cigarette
      smoke, indicating consumption of nitroxide radicals. To evaluate the ROS
      scavenging activity of the NRP-coated filter, the amount of peroxy radicals in an
      extract of cigarette smoke was measured using UV-visible spectrophotometry and
      1,1-diphenyl-2-picrylhydrazyl (DPPH). The absorbance of DPPH at 517 nm decreased
      with exposure to cigarette smoke. When NRP-coated filters were used, the decrease
      in the absorbance of DPPH was prevented. In contrast, both poly[4
      (cyclohexylamino)methylstyrene]- and poly(acrylic acid)-coated filters, which
      have no nitroxide radical, did not show any effect, indicating that the nitroxide
      radicals in the NRP scavenge the ROS in cigarette smoke. As a result, the extract
      of cigarette smoke passed through the NRP-coated filter has a lower cellular
      toxicity than smoke passed through poly[4-(cyclohexylamino)methylstyrene]- and
      poly(acrylic acid)-coated filters. Accordingly, NRP is a promising material for
      ROS scavenging from cigarette smoke.

PMID- 27877679
TI  - Detwining in Mg alloy with a high density of twin boundaries.
AB  - To investigate the role of preexisting twin boundaries in magnesium alloys during
      the deformation process, a large number of {10-12} tensile twins were introduced
      by a radial compression at room temperature before hot compressive tests with
      both low and high strain rates. Unlike the stable twins in Cu-based alloys with
      low stacking fault energies, {10-12} twins in Mg alloy are extremely unstable or
      easy to detwin through {10-12}-{10-12} re-twinning. As a result, non-lenticular
      residual twins and twin traces with misorientation of 5 degrees -7 degrees  were
      present, as confirmed by electron backscatter diffraction. The extreme
      instability of the twins during compression indicates that both twin and
      detwinning require extremely low resolved shear stresses under our experimental
      conditions.

PMID- 27877680
TI  - Improvement of the mode II interface fracture toughness of glass fiber reinforced
      plastics/aluminum laminates through vapor grown carbon fiber interleaves.
AB  - The effects of acid treatment, vapor grown carbon fiber (VGCF) interlayer and the
      angle, i.e., 0 degrees  and 90 degrees , between the rolling stripes of an
      aluminum (Al) plate and the fiber direction of glass fiber reinforced plastics
      (GFRP) on the mode II interlaminar mechanical properties of GFRP/Al laminates
      were investigated. The experimental results of an end notched flexure test
      demonstrate that the acid treatment and the proper addition of VGCF can
      effectively improve the critical load and mode II fracture toughness of GFRP/Al
      laminates. The specimens with acid treatment and 10 g m-2 VGCF addition possess
      the highest mode II fracture toughness, i.e., 269% and 385% increases in the 0
      degrees  and 90 degrees  specimens, respectively compared to those corresponding
      pristine ones. Due to the induced anisotropy by the rolling stripes on the
      aluminum plate, the 90 degrees  specimens possess 15.3%-73.6% higher mode II
      fracture toughness compared to the 0 degrees  specimens. The improvement
      mechanisms were explored by the observation of crack propagation path and
      fracture surface with optical, laser scanning and scanning electron microscopies.
      Moreover, finite element analyses were carried out based on the cohesive zone
      model to verify the experimental fracture toughness and to predict the interface
      shear strength between the aluminum plates and GFRP laminates.

PMID- 27877682
TI  - Energetic alignment in nontoxic SnS quantum dot-sensitized solar cell employing
      spiro-OMeTAD as the solid-state electrolyte.
AB  - An environmentally friendly solid-state quantum dot sensitized solar cell (ss
      QDSSC) was prepared by combining colloidal SnS QDs as the sensitizer and organic
      hole scavenger spiro-OMeTAD (2,2',7,7'-tetrakis-(N,N-di-p-methoxyphenylamine)9,9'
      spirobifluorene) as the solid-state electrolyte, and the energy alignment of SnS
      and TiO2 was investigated. The bandgap of colloidal SnS QDs increased with
      decreasing particle size from 14 to 4 nm due to an upshift of the conduction band
      and a downshift of the valence band. In TiO2/SnS heterojunctions, the conduction
      band minimum (CBM) difference between TiO2 and SnS was as large as ~0.8 eV; this
      difference decreased with decreasing particle size, but was sufficient for
      electron injection from SnS nanoparticles of any size into TiO2. Meanwhile, the
      sensitizer regeneration driving force, that is, the difference between the
      valence band maximum (VBM) of SnS and the work function of the electrolyte,
      showed an opposite behaviour with the SnS size due to a downward shift of the SnS
      VB. Consequently, smaller SnS QDs should result in a more efficient charge
      transfer in heterojunctions, revealing the advantages of QDs vs larger particles
      as sensitizers. This prediction was confirmed by the improved photovoltaic
      performance of ss-QDSSCs modified with SnS nanoparticles, which peaked for 5-6 nm
      sized SnS nanoparticles due to the balance between electron injection and
      sunlight absorption.

PMID- 27877681
TI  - Amperometric catechol biosensor based on laccase immobilized on nitrogen-doped
      ordered mesoporous carbon (N-OMC)/PVA matrix.
AB  - A functionalized nitrogen-containing ordered mesoporous carbon (N-OMC), which
      shows good electrical properties, was synthesized by the carbonization of
      polyaniline inside a SBA-15 mesoporous silica template. Based on this, through
      entrapping laccase onto the N-OMC/polyvinyl alcohol (PVA) film a facilely
      fabricated amperometric biosensor was developed. Laccase from Trametes versicolor
      was assembled on a composite film of a N-OMC/PVA modified Au electrode and the
      electrochemical behavior was investigated. The results indicated that the N-OMC
      modified electrode exhibits electrical properties towards catechol. The optimum
      experimental conditions of a biosensor for the detection of catechol were studied
      in detail. Under the optimal conditions, the sensitivity of the biosensor was
      0.29 A*M-1 with a detection limit of 0.31 MUM and a linear detection range from
      0.39 MUM to 8.98 MUM for catechol. The calibration curve followed the Michaelis
      Menten kinetics and the apparent Michaelis-Menten [Formula: see text] was 6.28
      MUM. This work demonstrated that the N-OMC/PVA composite provides a suitable
      support for laccase immobilization and the construction of a biosensor.

PMID- 27877683
TI  - Detection of segmentation cracks in top coat of thermal barrier coatings during
      plasma spraying by non-contact acoustic emission method.
AB  - Numerous cracks can be observed in the top coat of thermal barrier coatings
      (TBCs) deposited by the atmospheric plasma spraying (APS) method. These cracks
      can be classified into vertical and horizontal ones and they have opposite impact
      on the properties of TBCs. Vertical cracks reduce the residual stress in the top
      coat and provide strain tolerance. On the contrary, horizontal cracks trigger
      delamination of the top coat. However, monitoring methods of cracks generation
      during APS are rare even though they are strongly desired. Therefore, an in situ,
      non-contact and non-destructive evaluation method for this objective was
      developed in this study with the laser acoustic emission (AE) technique by using
      laser interferometers as a sensor. More AE events could be detected by
      introducing an improved noise reduction filter and AE event detection procedures
      with multiple thresholds. Generation of vertical cracks was successfully
      separated from horizontal cracks by a newly introduced scanning pattern of a
      plasma torch. Thus, generation of vertical cracks was detected with certainty by
      this monitoring method because AE events were detected only during spraying and a
      positive correlation was observed between the development degree of vertical
      cracks and the total AE energy in one experiment.

PMID- 27877684
TI  - Crafting ferromagnetism in Mn-doped MgO surfaces with p-type defects.
AB  - We have employed first-principles calculations based on density functional theory
      (DFT) to investigate the underlying physics of unusual magnetism in Mn-doped MgO
      surface. We have studied two distinct scenarios. In the first one, two Mn atoms
      are substitutionally added to the surface, occupying the Mg sites. Both are
      stabilized in the Mn[Formula: see text] valence state carrying a local moment of
      4.3 [Formula: see text] having a high-spin configuration. The magnetic
      interaction between the local moments display a very short-ranged characteristic,
      decaying very quickly with distance, and having antiferromagnetic ordering lower
      in energy. The energetics analysis also indicates that the Mn ions prefer to stay
      close to each other with an oxygen atom bridging the local interaction. In the
      second scenario, we started exploring the effect of native defects on the
      magnetism by crafting both Mg and O vacancies, which are p- and n-type defects,
      respectively. It is found that the electrons and holes affect the magnetic
      interaction between Mn ions in a totally different manner. The n-type defect
      leads to very similar magnetism, with the AFM configuration being energetically
      preferred. However, in the presence of Mg vacancy, the situation is quite
      different. The Mn atoms are further oxidized, giving rise to mixed Mn(d) ionic
      states. As a consequence, the Mn atoms couple ferromagnetically, when placed in
      the close configuration, and the obtained electronic structure is coherent with
      the double-exchange type of magnetic interaction. To guarantee the robustness of
      our results, we have benchmarked our calculations with three distinct theory
      levels, namely DFT-GGA, DFT-GGA+U and DFT-hybrid functionals. On the surface, the
      Mg vacancy displays lower formation energy occurring at higher concentrations.
      Therefore, our model systems can be the basis to explain a number of
      controversial results regarding transition metal doped oxides.

PMID- 27877685
TI  - Intermethod comparison of the particle size distributions of colloidal silica
      nanoparticles.
AB  - There can be a large variation in the measured diameter of nanoparticles
      depending on which method is used. In this work, we have strived to accurately
      determine the mean particle diameter of 30-40 nm colloidal silica particles by
      using six different techniques. A quantitative agreement between the particle
      size distributions was obtained by scanning electron microscopy (SEM), and
      electrospray-scanning mobility particle sizer (ES-SMPS). However, transmission
      electron microscopy gave a distribution shifted to smaller sizes. After
      confirming that the magnification calibration was consistent, this was attributed
      to sample preparation artifacts. The hydrodynamic diameter, dh , was determined
      by dynamic light scattering (DLS) both in batch mode, and hyphenated with
      sedimentation field flow fractionation. Surprisingly the dh were smaller than the
      SEM, and ES-SMPS diameters. A plausible explanation for the smaller sizes found
      with DLS is that a permeable gel layer forms on the particle surface. Results
      from nanoparticle tracking analysis were strongly biased towards larger
      diameters, most likely because the silica particles provide low refractive index
      contrast. Calculations confirmed that the sensitivity is, depending on the shape
      of the laser beam, strongly size dependent for particles with diameters close to
      the visualization limit.

PMID- 27877687
TI  - Controlling the length scale and distribution of the ductile phase in metallic
      glass composites through friction stir processing.
AB  - We demonstrate the refinement and uniform distribution of the crystalline
      dendritic phase by friction stir processing (FSP) of titanium based in situ
      ductile-phase reinforced metallic glass composite. The average size of the
      dendrites was reduced by almost a factor of five (from 24 MUm to 5 MUm) for the
      highest tool rotational speed of 900 rpm. The large inter-connected dendrites
      become more fragmented with increased circularity after processing. The changes
      in thermal characteristics were measured by differential scanning calorimetry.
      The reduction in crystallization enthalpy after processing suggests partial
      devitrification due to the high strain plastic deformation. FSP resulted in
      increased hardness and modulus for both the amorphous matrix and the crystalline
      phase. This is explained by interaction of shear bands in amorphous matrix with
      the strain-hardened dendritic phase. Our approach offers a new strategy for
      microstructural design in metallic glass composites.

PMID- 27877686
TI  - Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial
      growth factor induced angiogenesis.
AB  - Tumor growth depends on angiogenesis, which can furnish the oxygen and nutrients
      that proliferate tumor cells. Thus, blocking angiogenesis can be an effective
      strategy to inhibit tumor growth. In this work, three typical nanoparticles based
      on polyoxometalates (POMs) have been prepared; we investigated their capability
      as antitumor and anti-angiogenesis agents. We found that Mo POM nanoparticles,
      especially complex 3, inhibited the growth of human hepatocellular liver
      carcinoma cells (HepG2) through cellular reactive oxygen species levels'
      elevation and mitochondrial membrane potential damage. Complex 3 also suppressed
      the proliferation, migration, and tube formation of endothelial cells in vitro
      and chicken chorioallantoic membrane development ex vivo. Furthermore, western
      blot analysis of cell signaling molecules indicated that Mo POMs blocked the
      vascular endothelial growth factor receptor 2-mediated ERK1/2 and AKT signaling
      pathways in endothelial cells. Using transmission electron microscopy, we
      demonstrated their cellular uptake and localization within the cytoplasm of HepG2
      cells. These results indicate that, owing to the extraordinary physical and
      chemical properties, Mo POM nanoparticles can significantly inhibit tumor growth
      and angiogenesis, which makes them potential drug candidates in anticancer and
      anti-angiogenesis therapies.

PMID- 27877688
TI  - Theoretical and experimental investigation of the excellent p-n control in
      yttrium aluminoborides.
AB  - First-principles calculations were carried out to elucidate the excellent control
      of p-n characteristics recently reported for yttrium aluminoborides YxAlyB14
      [Formula: see text] with different occupancies of Al sites [Formula: see text].
      Such control of the occupancy of metal sites in borides is unusual. Calculations
      based on detailed x-ray diffraction data reveal a stable configuration of the
      atomic sites, indicating that such variation in occupancy is possible. A shift
      from positive through zero to negative values of the Seebeck coefficient is also
      clearly illustrated by determining the density of states for different
      configurations.

PMID- 27877689
TI  - Silica based polishing of {100} and {111} single crystal diamond.
AB  - Diamond is one of the hardest and most difficult to polish materials. In this
      paper, the polishing of {111} and {100} single crystal diamond surfaces by
      standard chemical mechanical polishing, as used in the silicon industry, is
      demonstrated. A Logitech Tribo Chemical Mechanical Polishing system with Logitech
      SF1 Syton and a polyurethane/polyester polishing pad was used. A reduction in
      roughness from 0.92 to 0.23 nm root mean square and 0.31 to 0.09 nm rms for {100}
      and {111} samples respectively was observed.

PMID- 27877690
TI  - First-principles study of electronic structures and stability of body-centered
      cubic Ti-Mo alloys by special quasirandom structures.
AB  - The electronic structures and structural properties of body-centered cubic Ti-Mo
      alloys were studied by first-principles calculations. The special quasirandom
      structures (SQS) model was adopted to emulate the solid solution state of the
      alloys. The valence band electronic structures of Ti-Mo and Ti-Mo-Fe alloys were
      measured by hard x-ray photoelectron spectroscopy. The structural parameters and
      valence band photoelectron spectra were calculated using first-principles
      calculations. The results obtained with the SQS models showed better agreement
      with the experimental results than those obtained using the conventional ordered
      structure models. This indicates that the SQS model is effective for predicting
      the various properties of solid solution alloys by means of first-principles
      calculations.

PMID- 27877691
TI  - Drastic influence of minor Fe or Co additions on the glass forming ability,
      martensitic transformations and mechanical properties of shape memory Zr-Cu-Al
      bulk metallic glass composites.
AB  - The microstructure and mechanical properties of Zr48Cu48 - x Al4M x (M = Fe or
      Co, x = 0, 0.5, 1 at.%) metallic glass (MG) composites are highly dependent on
      the amount of Fe or Co added as microalloying elements in the parent Zr48Cu48Al4
      material. Addition of Fe and Co promotes the transformation from austenite to
      martensite during the course of nanoindentation or compression experiments,
      resulting in an enhancement of plasticity. However, the presence of Fe or Co also
      reduces the glass forming ability, ultimately causing a worsening of the
      mechanical properties. Owing to the interplay between these two effects, the
      compressive plasticity for alloys with x = 0.5 (5.5% in Zr48Cu47.5Al4Co0.5 and
      6.2% in Zr48Cu47.5Al4Fe0.5) is considerably larger than for Zr48Cu48Al4 or the
      alloys with x = 1. Slight variations in the Young's modulus (around 5-10%) and
      significant changes in the yield stress (up to 25%) are also observed depending
      on the composition. The different microstructural factors that have an influence
      on the mechanical behavior of these composites are investigated in detail: (i) co
      existence of amorphous and crystalline phases in the as-cast state, (ii) nature
      of the crystalline phases (austenite versus martensite content), and (iii)
      propensity for the austenite to undergo a mechanically-driven martensitic
      transformation during plastic deformation. Evidence for intragranular nanotwins
      likely generated in the course of the austenite-martensite transformation is
      provided by transmission electron microscopy. Our results reveal that fine-tuning
      of the composition of the Zr-Cu-Al-(Fe,Co) system is crucial in order to optimize
      the mechanical performance of these bulk MG composites, to make them suitable
      materials for structural applications.

PMID- 27877692
TI  - Mechanical response of melt-spun amorphous filaments.
AB  - High-speed melt spinning of a cyclo-olefin polymer (COP) and a copolyamide (CoPA)
      have been performed. Differential scanning calorimetry curves of the resulting
      monofilaments show that they remain in an amorphous state even after hot drawing.
      Wide angle x-ray diffraction patterns of undrawn and drawn COP filaments show
      that although the material remains in an amorphous state, a degree of orientation
      is induced in the polymer after drawing. The amorphous filaments show an enhanced
      bending recovery with respect to different semi-crystalline monofilaments
      commercially available. However, single fiber axial compressive testing indicates
      that the amorphous filaments exhibit a compressive modulus value which is 50%
      lower than what is observed for a reference semi-crystalline PET filament.
      Analysis of the compressive strains applied by the bending recovery test
      indicates that while the maximum applied strains remain well within the region of
      elastic deformation of the amorphous materials, the threshold between elastic and
      plastic deformation is reached for the semi-crystalline materials.

PMID- 27877693
TI  - Focus on organic electronics.

PMID- 27877694
TI  - Recent research progress on iron- and manganese-based positive electrode
      materials for rechargeable sodium batteries.
AB  - Large-scale high-energy batteries with electrode materials made from the Earth
      abundant elements are needed to achieve sustainable energy development. On the
      basis of material abundance, rechargeable sodium batteries with iron- and
      manganese-based positive electrode materials are the ideal candidates for large
      scale batteries. In this review, iron- and manganese-based electrode materials,
      oxides, phosphates, fluorides, etc, as positive electrodes for rechargeable
      sodium batteries are reviewed. Iron and manganese compounds with sodium ions
      provide high structural flexibility. Two layered polymorphs, O3- and P2-type
      layered structures, show different electrode performance in Na cells related to
      the different phase transition and sodium migration processes on sodium
      extraction/insertion. Similar to layered oxides, iron/manganese phosphates and
      pyrophosphates also provide the different framework structures, which are used as
      sodium insertion host materials. Electrode performance and reaction mechanisms of
      the iron- and manganese-based electrode materials in Na cells are described and
      the similarities and differences with lithium counterparts are also discussed.
      Together with these results, the possibility of the high-energy battery system
      with electrode materials made from only Earth-abundant elements is reviewed.

PMID- 27877695
TI  - Current advances in precious metal core-shell catalyst design.
AB  - Precious metal nanoparticles are commonly used as the main active components of
      various catalysts. Given their high cost, limited quantity, and easy loss of
      catalytic activity under severe conditions, precious metals should be used in
      catalysts at low volumes and be protected from damaging environments.
      Accordingly, reducing the amount of precious metals without compromising their
      catalytic performance is difficult, particularly under challenging conditions. As
      multifunctional materials, core-shell nanoparticles are highly important owing to
      their wide range of applications in chemistry, physics, biology, and
      environmental areas. Compared with their single-component counterparts and other
      composites, core-shell nanoparticles offer a new active interface and a potential
      synergistic effect between the core and shell, making these materials highly
      attractive in catalytic application. On one hand, when a precious metal is used
      as the shell material, the catalytic activity can be greatly improved because of
      the increased surface area and the closed interfacial interaction between the
      core and the shell. On the other hand, when a precious metal is applied as the
      core material, the catalytic stability can be remarkably improved because of the
      protection conferred by the shell material. Therefore, a reasonable design of the
      core-shell catalyst for target applications must be developed. We summarize the
      latest advances in the fabrications, properties, and applications of core-shell
      nanoparticles in this paper. The current research trends of these core-shell
      catalysts are also highlighted.

PMID- 27877697
TI  - A density functional theory investigation of the electronic structure and spin
      moments of magnetite.
AB  - We present the results of density functional theory (DFT) calculations on
      magnetite, Fe3O4, which has been recently considered as electrode in the emerging
      field of organic spintronics. Given the nature of the potential applications, we
      evaluated the magnetite room-temperature cubic [Formula: see text] phase in terms
      of structural, electronic, and magnetic properties. We considered GGA (PBE), GGA
      + U (PBE + U), and range-separated hybrid (HSE06 and HSE(15%)) functionals.
      Calculations using HSE06 and HSE(15%) functionals underline the impact that
      inclusion of exact exchange has on the electronic structure. While the modulation
      of the band gap with exact exchange has been seen in numerous situations, the
      dramatic change in the valence band nature and states near the Fermi level has
      major implications for even a qualitative interpretation of the DFT results. We
      find that HSE06 leads to highly localized states below the Fermi level while
      HSE(15%) and PBE + U result in delocalized states around the Fermi level. The
      significant differences in local magnetic moments and atomic charges indicate
      that describing room-temperature bulk materials, surfaces and interfaces may
      require different functionals than their low-temperature counterparts.

PMID- 27877698
TI  - Helically assembled pi-conjugated polymers with circularly polarized
      luminescence.
AB  - We review the recent progress in the field of helically assembled pi-conjugated
      polymers, focusing on aromatic conjugated polymers with interchain helical pi
      stacking that exhibit circularly polarized luminescence (CPL). In Part 1, we
      discuss optically active polymers with white-colored CPL and the amplification of
      the circular polarization through liquid crystallinity. In Part 2, we focus on
      the stimuli-responsive CPL that results from changes in the conformation and
      aggregation state of pi-conjugated molecules and polymers. In Part 3, we discuss
      the self-assembly of achiral cationic pi-conjugated polymers into circularly
      polarized luminescent supramolecular nanostructures with the aid of other chiral
      molecules.

PMID- 27877699
TI  - Magnetism in icosahedral quasicrystals: current status and open questions.
AB  - Progress in our understanding of the magnetic properties of R-containing
      icosahedral quasicrystals (R = rare earth element) from over 20 years of
      experimental effort is reviewed. This includes the much studied R-Mg-Zn and R-Mg
      Cd ternary systems, as well as several magnetic quasicrystals that have been
      discovered and investigated more recently including Sc-Fe-Zn, R-Ag-In, Yb-Au-Al,
      the recently synthesized R-Cd binary quasicrystals, and their periodic
      approximants. In many ways, the magnetic properties among these quasicrystals are
      very similar. However, differences are observed that suggest new experiments and
      promising directions for future research.

PMID- 27877696
TI  - Pd- and Ni-catalyzed cross-coupling reactions in the synthesis of organic
      electronic materials.
AB  - Organic molecules and polymers with extended pi-conjugation are appealing as
      advanced electronic materials, and have already found practical applications in
      thin-film transistors, light emitting diodes, and chemical sensors. Transition
      metal (TM)-catalyzed cross-coupling methodologies have evolved over the past four
      decades into one of the most powerful and versatile methods for C-C bond
      formation, enabling the construction of a diverse and sophisticated range of pi
      conjugated oligomers and polymers. In this review, we focus our discussion on
      recent synthetic developments of several important classes of pi-conjugated
      systems using TM-catalyzed cross-coupling reactions, with a perspective on their
      utility for organic electronic materials.

PMID- 27877700
TI  - Metallic-covalent bonding conversion and thermoelectric properties of Al-based
      icosahedral quasicrystals and approximants.
AB  - In this article, we review the characteristic features of icosahedral cluster
      solids, metallic-covalent bonding conversion (MCBC), and the thermoelectric
      properties of Al-based icosahedral quasicrystals and approximants. MCBC is
      clearly distinguishable from and closely related to the well-known metal
      insulator transition. This unique bonding conversion has been experimentally
      verified in 1/1-AlReSi and 1/0-Al12Re approximants by the maximum entropy method
      and Rietveld refinement for powder x-ray diffraction data, and is caused by a
      central atom inside the icosahedral clusters. This helps to understand pseudogap
      formation in the vicinity of the Fermi energy and establish a guiding principle
      for tuning the thermoelectric properties. From the electron density distribution
      analysis, rigid heavy clusters weakly bonded with glue atoms are observed in the
      1/1-AlReSi approximant crystal, whose physical properties are close to
      icosahedral Al-Pd-TM (TM: Re, Mn) quasicrystals. They are considered to be an
      intermediate state among the three typical solids: metals, covalently bonded
      networks (semiconductor), and molecular solids. Using the above picture and
      detailed effective mass analysis, we propose a guiding principle of weakly bonded
      rigid heavy clusters to increase the thermoelectric figure of merit (ZT) by
      optimizing the bond strengths of intra- and inter-icosahedral clusters. Through
      element substitutions that mainly weaken the inter-cluster bonds, a dramatic
      increase of ZT from less than 0.01 to 0.26 was achieved. To further increase ZT,
      materials should form a real gap to obtain a higher Seebeck coefficient.

PMID- 27877701
TI  - Tailoring microstructure of Mg-Zn-Y alloys with quasicrystal and related phases
      for high mechanical strength.
AB  - The occurrence of a stable icosahedral (i-) phase, which is quasicrystalline with
      an icosahedral (fivefold) symmetry, on the equilibrium phase diagram of Mg-Zn-RE
      (RE = Y, Gd, Tb, Dy, Ho or Er) alloys opened up an interesting possibility of
      developing a new series of magnesium alloys for structural applications. Alloys
      based on the i-phase have been studied for the past 14 years. Ultra-high
      strengths combined with good ductility have been shown. Here we show two
      strategies for tailoring microstructures for very high strengths in Mg-Zn-Y
      alloys. One of them involves strengthening by a fine distribution of rod-like
      [Formula: see text] precipitates, where the matrix grain size is not critical.
      The alloy is solutionized at a high temperature of 480  degrees C to dissolve a
      large part of the i-phase, followed by a high temperature extrusion (~430 
      degrees C) and a low temperature ageing to reprecipitate phases with fine size
      distribution. At first, phase transformations involved in this procedure are
      described. The closeness of the structure of the [Formula: see text] precipitates
      to the i-phase is brought out. By this procedure, tensile yield strengths of over
      370 MPa are obtained in grain sizes of 20 MUm. In another strategy, the alloys
      are chill cast and then extruded at low temperatures of about 250  degrees C.
      Ultra-fine grains are produced by enhanced recrystallization due to presence of
      the i-phase. At the same time nano-sized precipitates are precipitated
      dynamically during extrusion from the supersaturated matrix. Ultra-high tensile
      strengths of up to 400 MPa are obtained in combination with ductility of 12 to
      16%. Analysis of the microstructure shows that strengthening by the i-phase
      occurs by enhanced recrystallization during extrusion. It produces ultra-fine
      grain sizes to give very high strengths, and moderate texture for good ductility.
      Fine distribution of the i-phase and precipitates contribute to strengthening and
      provide microstructre stability. Ultra-high strength over a very wide range of
      grain sizes is thus demonstrated, by utilizing different strengthening effects.

PMID- 27877702
TI  - Ambience-sensitive optical refraction in ferroelectric nanofilms of NaNbO3.
AB  - Optical index of refraction n is studied by spectroscopic ellipsometry in
      epitaxial nanofilms of NaNbO3 with thickness ~10 nm grown on different single
      crystal substrates. The index n in the transparency spectral range (n ~ 2.1 -
      2.2) exhibits a strong sensitivity to atmospheric-pressure gas ambience. The
      index n in air exceeds that in an oxygen ambience by deltan ~ 0.05 - 0.2. The
      thermo-optical behaviour n(T) indicates ferroelectric state in the nanofilms. The
      ambience-sensitive optical refraction is discussed in terms of fundamental
      connection between refraction and ferroelectric polarization in perovskites,
      screening of depolarizing field on surfaces of the nanofilms, and
      thermodynamically stable surface reconstructions of NaNbO3.

PMID- 27877703
TI  - Manipulation of cell membrane using carbon nanotube scaffold as a photoresponsive
      stimuli generator.
AB  - We describe, for the first time, the perforation of the cell membrane in the
      targeted single cell based on the nanosecond pulsed near-infrared (NIR) laser
      irradiation of a thin film of carbon nanotubes that act as an effective photon
      absorber as well as stimuli generator. When the power of NIR laser is over 17.5
      MUJ/pulse, the cell membrane after irradiation is irreversibly disrupted and
      results in cell death. In sharp contrast, the perforation of the cell membrane
      occurs at suitable laser power (~15 MUJ/pulse) without involving cell
      termination.

PMID- 27877704
TI  - Rapid sintering of silicon nitride foams decorated with one-dimensional
      nanostructures by intense thermal radiation.
AB  - Silicon nitride foams were prepared by direct foaming and subsequent rapid
      sintering at 1600  degrees C. The intense thermal radiation generated under the
      pressureless spark plasma sintering condition facilitated necking of Si3N4
      grains. The prepared foams possessed a porosity of ~80 vol% and a compressive
      strength of ~10 MPa, which required only ~30 min for the entire sintering
      processes. Rapid growth of one-dimensional SiC nanowires from the cell walls was
      also observed. Thermodynamic calculations indicated that the vapor-liquid-solid
      model is applicable to the formation of SiC nanowires under vacuum.

PMID- 27877705
TI  - Free-standing alumina nanobottles and nanotubes pre-integrated into nanoporous
      alumina membranes.
AB  - A novel interfacial structure consisting of long (up to 5 MUm), thin (about 300
      nm), highly-ordered, free-standing, highly-reproducible aluminum oxide
      nanobottles and long tubular nanocapsules attached to a rigid, thin (less than 1
      MUm) nanoporous anodic alumina membrane is fabricated by simple, fast, catalyst
      free, environmentally friendly voltage-pulse anodization. A growth mechanism is
      proposed based on the formation of straight channels in alumina membrane by
      anodization, followed by neck formation due to a sophisticated voltage control
      during the process. This process can be used for the fabrication of alumina
      nanocontainers with highly controllable geometrical size and volume, vitally
      important for various applications such as material and energy storage, targeted
      drug and diagnostic agent delivery, controlled drug and active agent release,
      gene and biomolecule reservoirs, micro-biologically protected platforms, nano
      bioreactors, tissue engineering and hydrogen storage.

PMID- 27877706
TI  - Ratchet effect study in Si/SiGe heterostructures in the presence of asymmetrical
      antidots for different polarizations of microwaves.
AB  - In this work, we studied the photovoltage response of an antidot lattice to
      microwave radiation for different antidot parameters. The study was carried out
      in a Si/SiGe heterostructure by illuminating the antidot lattice with linearly
      polarized microwaves and recording the polarity of induced photovoltage for
      different angles of incidence. Our study revealed that with increased antidot
      density and etching depth, the polarity of induced photovoltage changed when the
      angle of incidence was rotated 90 degrees. In samples with large antidot density
      and/or a deeply etched antidot lattice, scattering was dominated by electron
      interaction with the asymmetrical potential created by semicircular antidots. The
      strong electron-electron interaction prevailed in other cases. Our study provides
      insight into the mechanism of interaction between microwaves and electrons in an
      antidot lattice, which is the key for developing an innovative ratchet-based
      device. Moreover, we present an original and fundamental example of antidot
      lattice etching through the use of a two-dimensional electron gas. This system
      deals with a hole lattice instead of an electron depletion in the antidot lattice
      region.

PMID- 27877709
TI  - Preface: Focus on complex metallic phases.

PMID- 27877708
TI  - A soluble biocompatible guanidine-containing polyamidoamine as promoter of
      primary brain cell adhesion and in vitro cell culturing.
AB  - This paper reports on a novel application of an amphoteric water-soluble
      polyamidoamine named AGMA1 bearing 4-butylguanidine pendants. AGMA1 is an
      amphoteric, prevailingly cationic polyelectrolyte with isoelectric point of about
      10. At pH 7.4 it is zwitterionic with an average of 0.55 excess positive charges
      per unit, notwithstanding it is highly biocompatible. In this work, it was found
      that AGMA1 surface-adsorbed on cell culturing coverslips exhibits excellent
      properties as adhesion and proliferation promoter of primary brain cells such as
      microglia, as well as of hippocampal neurons and astrocytes. Microglia cells
      cultured on AGMA1-coated coverslips substrate displayed the typical resting,
      ramified morphology of those cultured on poly-L-lysine and poly-L-ornithine,
      employed as reference substrates. Mixed cultures of primary astrocytes and
      neuronal cells grown on AGMA1- and poly-L-lysine coated coverslips were
      morphologically undistinguishable. On both substrates, neurons differentiated
      axon and dendrites and eventually established perfectly functional synaptic
      contacts. Quantitative immunocytochemical staining revealed no difference between
      AGMA1 and poly-L-lysine. Electrophysiological experiments allowed recording
      neuron spontaneous activity on AGMA1. In addition, cell cultures on both AGMA1
      and PLL displayed comparable excitatory and inhibitory neurotransmission,
      demonstrating that the synaptic contacts formed were fully functional.

PMID- 27877710
TI  - Foreword: Focus on complex metallic phases.
AB  - I am glad to learn that a focus issue, Complex Metallic Phases, will be published
      in Science and Technology of Advanced Materials (STAM). The articles in this
      special issue contain original and review papers on fundamentals and applications
      contributed by experts in the field. The topics cover various approaches to
      practical applications including catalysts, photonics, high specific strength
      materials, thermal storage materials and thermal rectification for quasicrystals,
      as well as related complex compounds. It is exciting to see the great potential
      of these complex phases, and I look forward to seeing their industrial
      applications in the foreseeable future. [Formula: see text] Professor Dan
      Shechtman Recepient of the Nobel Prize in Chemistry 2011 for his discovery of
      'quasi-crystals' in 1984.

PMID- 27877707
TI  - Preparation of epigallocatechin gallate-loaded nanoparticles and characterization
      of their inhibitory effects on Helicobacter pylori growth in vitro and in vivo.
AB  - A variety of approaches have been proposed for overcoming the unpleasant side
      effects associated with antibiotics treatment of Helicobacter pylori (H. pylori)
      infections. Research has shown that epigallocatechin-3-gallate (EGCG), a major
      ingredient in green tea, has antibacterial activity for antiurease activity
      against H. pylori. Oral EGCG is not good because of its digestive instability and
      the fact that it often cannot reach the targeted site of antibacterial activity.
      To localize EGCG to H. pylori infection site, this study developed a fucose
      chitosan/gelatin nanoparticle to encapsulate EGCG at the target and make direct
      contact with the region of microorganisms on the gastric epithelium. Analysis of
      a simulated gastrointestinal medium indicated that the proposed in vitro
      nanocarrier system effectively controls the release of EGCG, which interacts
      directly with the intercellular space at the site of H. pylori infection.
      Meanwhile, results of in vivo clearance assays indicated that our prepared fucose
      chitosan/gelatin/EGCG nanoparticles had a significantly greater H. pylori
      clearance effect and more effectively reduced H. pylori-associated gastric
      inflammation in the gastric-infected mouse model than the EGCG solution alone.

PMID- 27877711
TI  - Localized photovoltaic investigations on organic semiconductors and bulk
      heterojunction solar cells.
AB  - Newly synthesized organic electronics materials are often available in
      submicrogram amounts only. Photoelectrochemical scanning droplet cell microscopy
      is a powerful method that allows a comprehensive characterisation of such small
      amounts including oxidation, reduction potentials, doping, determination of
      charge carriers, band gap, charge capacity, over-oxidation sensitivity and many
      more. Localized photoelectrochemical characterization of the poly[4,8-bis
      substituted-benzo[1,2-b:4,5-b0]dithiophene-2,6-diyl-alt-4-substituted-thieno [3,4
      b] thiophene-2,6-diyl] (PBDTTT-c) and PBDTTT-c:PCBM bulk heterojunction was
      performed using photoelectrochemical scanning droplet cell microscopy (PE-SDCM).
      The optical properties and the real and imaginary part of the dielectric
      function, of the polymer were determined using spectroscopic ellipsometry. The
      photoelectrochemical characterizations were performed in a three and two
      electrode configuration of PE-SDCM under laser and white light illumination. The
      effect of illumination was characterized using dark/illumination sequences. The
      stability of the photocurrent was studied using longer term (600 s) illumination.
      Finally the effect of cell configuration and illumination conditions on the
      photovoltage was studied.

PMID- 27877712
TI  - Phosphorescent cyclometalated complexes for efficient blue organic light-emitting
      diodes.
AB  - Phosphorescent emitters are extremely important for efficient organic light
      emitting diodes (OLEDs), which attract significant attention. Phosphorescent
      emitters, which have a high phosphorescence quantum yield at room temperature,
      typically contain a heavy metal such as iridium and have been reported to emit
      blue, green and red light. In particular, the blue cyclometalated complexes with
      high efficiency and high stability are being developed. In this review, we focus
      on blue cyclometalated complexes. Recent progress of computational analysis
      necessary to design a cyclometalated complex is introduced. The prediction of the
      radiative transition is indispensable to get an emissive cyclometalated complex.
      We summarize four methods to control phosphorescence peak of the cyclometalated
      complex: (i) substituent effect on ligands, (ii) effects of ancillary ligands on
      heteroleptic complexes, (iii) design of the ligand skeleton, and (iv) selection
      of the central metal. It is considered that novel ligand skeletons would be
      important to achieve both a high efficiency and long lifetime in the blue OLEDs.
      Moreover, the combination of an emitter and a host is important as well as the
      emitter itself. According to the dependences on the combination of an emitter and
      a host, the control of exciton density of the triplet is necessary to achieve
      both a high efficiency and a long lifetime, because the annihilations of the
      triplet state cause exciton quenching and material deterioration.

PMID- 27877713
TI  - Synthesis of N-acetyl-L-cysteine-capped ZnCdSe quantum dots via hydrothermal
      method and their characterization.
AB  - Compared with the most studied green-red emitting (530-650 nm) quantum dots
      (QDs), the preparation of short-wavelength-emitting QDs remains difficult.
      Besides, one of the representative short-wavelength QDs materials, ZnCdSe, has a
      shortcoming of high content of toxic cadmium metal. In this paper, we report the
      synthesis of high-quality water-soluble ZnCdSe QDs via optimized one-step
      hydrothermal method with a new thiol as ligand, within a short time of 65 min.
      The emission wavelength of prepared QDs is tunable in the range of 425-540 nm by
      merely controlling the molar ratio of Cd:Zn or Se:Zn, and the quantum yield
      reaches 35%. More importantly, the maximum Cd:Zn molar ratio has been reduced to
      0.04:1.0, much lower than that reported in the literature (0.5:1.0), resulting in
      excellent biological compatibility of prepared QDs and thus their promising
      applications in biological fields. Moreover, the transmission electron microscopy
      was employed to examine the effect of Cd:Zn ratio on the size of prepared ZnCdSe
      QDs, which were also characterized by x-ray photoelectron spectroscopy and
      electron diffraction spectroscopy.

PMID- 27877714
TI  - Modification of the structural and electrical properties of graphene layers by Pt
      adsorbates.
AB  - The properties of graphene are strongly affected by metal adsorbates and clusters
      on graphene. Here, we study the effect of a thin layer of platinum (Pt) metal on
      exfoliated single, bi- and trilayer graphene and on chemical vapor deposition
      grown single-layer graphene by using Raman spectroscopy and transport
      measurements. The Raman spectra and transport measurements show that Pt affects
      the structure as well as the electronic properties of graphene. The shift of peak
      frequencies, intensities and widths of the Raman bands were analyzed after the
      deposition of Pt with different thicknesses (1, 3, 5 nm) on the graphene. The
      shifts in the G and 2D peak positions of the Raman spectra indicate the n-type
      doping effect by the Pt metal. The doping effect was also confirmed by gate
      voltage dependent resistivity measurements. The doping effect by the Pt metal is
      stable under ambient conditions, and the doping intensity increases with the
      increasing Pt deposition without inducing a severe degradation of the charge
      carrier mobility.

PMID- 27877715
TI  - Effects of ozone nano-bubble water on periodontopathic bacteria and oral cells -
      in vitro studies.
AB  - The aims of the present study were to evaluate the bactericidal activity of a new
      antiseptic agent, ozone nano-bubble water (NBW3), against periodontopathogenic
      bacteria and to assess the cytotoxicity of NBW3 against human oral cells. The
      bactericidal activities of NBW3 against representative periodontopathogenic
      bacteria, Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter
      actinomycetemcomitans (A. actinomycetemcomitans) were evaluated using in vitro
      time-kill assays. The cytotoxicity of NBW3 was evaluated using three-dimensional
      human buccal and gingival tissue models. The numbers of colony forming units
      (CFUs)/mL of P. gingivalis and A. actinomycetemcomitans exposed to NBW3 dropped
      to below the lower limit of detection (<10 CFUs mL-1) after only 0.5 min of
      exposure. There were only minor decreases in the viability of oral tissue cells
      after 24 h of exposure to NBW3. These results suggest that NBW3 possesses potent
      bactericidal activity against representative periodontopathogenic bacteria and is
      not cytotoxic to cells of human oral tissues. The use of NBW3 as an adjunct to
      periodontal therapy would be promising.

PMID- 27877716
TI  - Improving the electrical properties of graphene layers by chemical doping.
AB  - Although the electronic properties of graphene layers can be modulated by various
      doping techniques, most of doping methods cost degradation of structural
      uniqueness or electrical mobility. It is matter of huge concern to develop a
      technique to improve the electrical properties of graphene while sustaining its
      superior properties. Here, we report the modification of electrical properties of
      single- bi- and trilayer graphene by chemical reaction with potassium nitrate
      (KNO3) solution. Raman spectroscopy and electrical transport measurements showed
      the n-doping effect of graphene by KNO3. The effect was most dominant in single
      layer graphene, and the mobility of single layer graphene was improved by the
      factor of more than 3. The chemical doping by using KNO3 provides a facile
      approach to improve the electrical properties of graphene layers sustaining their
      unique characteristics.

PMID- 27877717
TI  - Photoluminescence and doping mechanism of theranostic Eu3+/Fe3+ dual-doped
      hydroxyapatite nanoparticles.
AB  - Theranostic nanoparticles currently have been regarded as an emerging concept of
      'personalized medicine' with diagnostic and therapeutic dual-functions. Eu3+
      doped hydroxyapatite (HAp) has been regarded as a promising fluorescent probe for
      in vivo imaging applications. Additionally, substitution of Ca2+ with Fe3+ in HAp
      crystal may endow the capability of producing heat upon exposure to a magnetic
      field. Here we report a preliminary study of doping mechanism and
      photoluminescence of Eu3+ and Fe3+ doped HAp nanoparticles (Eu/Fe:HAp). HAp with
      varied concentration of Eu3+ and Fe3+ doping are presented as Eu(10 mol%):HAp,
      Eu(7 mol%)-Fe(3 mol%):HAp, Eu(5 mol%)-Fe(5 mol%):HAp, Eu(3 mol%)-Fe(7 mol%):HAp,
      and Fe(10 mol%):HAp in the study. The results showed that the HAp particles, in
      nano-size with rod-like morphology, were successfully doped with Eu3+ and Fe3+,
      and the particles can be well suspended in cell culture medium. Photoluminescence
      analysis revealed that particles have prominent emissions at 536 nm, 590 nm, 615
      nm, 650 nm and 695 nm upon excitation at a wavelength of 397 nm. Moreover, these
      Eu/Fe:HAp nanoparticles belonged to B-type carbonated HAp, which has been
      considered an effective biodegradable and biocompatible drug/gene carrier in
      biological applications.

PMID- 27877718
TI  - Enhanced photoelectrochemical properties of TiO2 nanorod arrays decorated with
      CdS nanoparticles.
AB  - TiO2 nanorod arrays (TiO2 NRAs) sensitized with CdS nanoparticles were fabricated
      via successive ion layer adsorption and reaction (SILAR), and TiO2 NRAs were
      obtained by oxidizing Ti NRAs obtained through oblique angle deposition. The TiO2
      NRAs decorated with CdS nanoparticles exhibited excellent photoelectrochemical
      and photocatalytic properties under visible light, and the one decorated with 20
      SILAR cycles CdS nanoparticles shows the best performance. This can be attributed
      to the enhanced separation of electrons and holes by forming heterojunctions of
      CdS nanoparticles and TiO2 NRAs. This provides a promising way to fabricate the
      material for solar energy conversion and wastewater degradation.

PMID- 27877719
TI  - Pressure-dependent magnetization and magnetoresistivity studies on tetragonal FeS
      (mackinawite): revealing its intrinsic metallic character.
AB  - The transport and magnetic properties of the tetragonal Fe[Formula: see text]S
      were investigated using magnetoresistivity and magnetization within [Formula: see
      text] K, [Formula: see text] 70 kOe and [Formula: see text] 3.0 GPa. In addition,
      room-temperature x-ray diffraction and photoelectron spectroscopy were also
      applied. In contrast to previously reported nonmetallic character, Fe[Formula:
      see text]S is intrinsically metallic but due to a presence of a weak localization
      such metallic character is not exhibited below room temperature. An applied
      pressure reduces strongly this additional resistive contribution and as such
      enhances the temperature range of the metallic character which, for ~3 GPa, is
      evident down to 75 K. The absence of superconductivity as well as the mechanism
      behind the weak localization will be discussed.

PMID- 27877720
TI  - The electro-structural behaviour of yarn-like carbon nanotube fibres immersed in
      organic liquids.
AB  - Yarn-like carbon nanotube (CNT) fibres are a hierarchically-structured material
      with a variety of promising applications such as high performance composites,
      sensors and actuators, smart textiles, and energy storage and transmission.
      However, in order to fully realize these possibilities, a more detailed
      understanding of their interactions with the environment is required. In this
      work, we describe a simplified representation of the hierarchical structure of
      the fibres from which several mathematical models are constructed to explain
      electro-structural interactions of fibres with organic liquids. A balance between
      the elastic and surface energies of the CNT bundle network in different media
      allows the determination of the maximum lengths that open junctions can sustain
      before collapsing to minimize the surface energy. This characteristic length
      correlates well with the increase of fibre resistance upon immersion in organic
      liquids. We also study the effect of charge accumulation in open interbundle
      junctions and derive expressions to describe experimental data on the non-ohmic
      electrical behaviour of fibres immersed in polar liquids. Our analyses suggest
      that the non-ohmic behaviour is caused by progressively shorter junctions
      collapsing as the voltage is increased. Since our models are not based on any
      property unique to carbon nanotubes, they should also be useful to describe other
      hierarchical structures.

PMID- 27877721
TI  - Vertically-aligned graphene flakes on nanoporous templates: morphology,
      thickness, and defect level control by pre-treatment.
AB  - Various morphologies of the vertically-aligned graphene flakes were fabricated on
      the nanoporous templates treated with metal ions in solutions, as well as coated
      with a thin gold layer and activated in the low-temperature Ar plasma. The
      thickness and level of structural defects in the graphene flakes could be
      effectively controlled by a proper selection of the pre-treatment method. We have
      also demonstrated that various combinations of the flake thickness and defect
      levels can be obtained, and the morphology and density of the graphene pattern
      can be effectively controlled. The result obtained could be of interest for
      various applications requiring fabrication of large graphene networks with
      controllable properties.

PMID- 27877722
TI  - Precise control over shape and size of iron oxide nanocrystals suitable for
      assembly into ordered particle arrays.
AB  - Here we demonstrate how monodisperse iron oxide nanocubes and nanospheres with
      average sizes between 5 and 27 nm can be synthesized by thermal decomposition.
      The relative importance of the purity of the reactants, the ratio of oleic acid
      and sodium oleate, the maximum temperature, and the rate of temperature increase,
      on robust and reproducible size and shape-selective iron oxide nanoparticle
      synthesis are identified and discussed. The synthesis conditions that generate
      highly monodisperse iron oxide nanocubes suitable for producing large ordered
      arrays, or mesocrystals are described in detail.

PMID- 27877723
TI  - Atomically precise cluster catalysis towards quantum controlled catalysts.
AB  - Catalysis of atomically precise clusters supported on a substrate is reviewed in
      relation to the type of reactions. The catalytic activity of supported clusters
      has generally been discussed in terms of electronic structure. Several lines of
      evidence have indicated that the electronic structure of clusters and the
      geometry of clusters on a support, including the accompanying cluster-support
      interaction, are strongly correlated with catalytic activity. The electronic
      states of small clusters would be easily affected by cluster-support
      interactions. Several studies have suggested that it is possible to tune the
      electronic structure through atomic control of the cluster size. It is promising
      to tune not only the number of cluster atoms, but also the hybridization between
      the electronic states of the adsorbed reactant molecules and clusters in order to
      realize a quantum-controlled catalyst.

PMID- 27877724
TI  - Anomalous transport phenomena in Weyl metal beyond the Drude model for Landau's
      Fermi liquids.
AB  - Landau's Fermi-liquid theory is the standard model for metals, characterized by
      the existence of electron quasiparticles near a Fermi surface as long as Landau's
      interaction parameters lie below critical values for instabilities. Recently this
      fundamental paradigm has been challenged by the physics of strong spin-orbit
      coupling, although the concept of electron quasiparticles remains valid near the
      Fermi surface, where Landau's Fermi-liquid theory fails to describe the
      electromagnetic properties of this novel metallic state, referred to as Weyl
      metal. A novel ingredient is that such a Fermi surface encloses a Weyl point with
      definite chirality, referred to as a chiral Fermi surface, which can arise from
      breaking of either time reversal or inversion symmetry in systems with strong
      spin-orbit coupling, responsible for both the Berry curvature and the chiral
      anomaly. As a result, electromagnetic properties of the Weyl metallic state are
      described not by conventional Maxwell equations but by axion electrodynamics,
      where Maxwell equations are modified with a topological-in-origin spatially
      modulated [Formula: see text] term. This novel metallic state was realized
      recently in Bi[Formula: see text]Sb x around [Formula: see text] under magnetic
      fields, where the Dirac spectrum appears around the critical point between the
      normal semiconducting ([Formula: see text]) and topological semiconducting phases
      ([Formula: see text]) and the time reversal symmetry breaking perturbation causes
      the Dirac point to split into a pair of Weyl points along the direction of the
      applied magnetic field for a very strong spin-orbit coupled system. In this
      review article, we discuss how the topological structure of both the Berry
      curvature and the chiral anomaly (axion electrodynamics) gives rise to anomalous
      transport phenomena in [Formula: see text]Sb x around [Formula: see text] under
      magnetic fields, thus modifying the Drude model of Landau's Fermi liquids.

PMID- 27877725
TI  - New scheme for braiding Majorana fermions.
AB  - Non-Abelian statistics can be achieved by exchanging two vortices in topological
      superconductors with each grabbing a Majorana fermion (MF) as zero-energy quasi
      particle at the cores. However, in experiments it is difficult to manipulate
      vortices. In the present work, we propose a way to braid MFs without moving
      vortices. The only operation required in the present scheme is to turn on and off
      local gate voltages, which liberates a MF from its original host vortex and
      transports it along the prepared track. We solve the time-dependent Bogoliubov-de
      Gennes equation numerically, and confirm that the MFs are protected provided the
      switching of gate voltages for exchanging MFs are adiabatic, which takes only
      several nano seconds given reasonable material parameters. By monitoring the time
      evolution of MF wave-functions, we show that non-Abelian statistics is achieved.

PMID- 27877726
TI  - Adiabatic photo-steering theory in topological insulators.
AB  - Feasible external control of material properties is a crucial issue in condensed
      matter physics. A new approach to achieving this aim, named adiabatic photo
      steering, is reviewed. The core principle of this scheme is that several material
      constants are effectively turned into externally tunable variables by irradiation
      of monochromatic laser light. Two-dimensional topological insulators are selected
      as the optimal systems that exhibit a prominent change in their properties
      following the application of this method. Two specific examples of photo-steered
      quantum phenomena, which reflect topological aspects of the electronic systems at
      hand, are presented. One is the integer quantum Hall effect described by the
      Haldane model, and the other is the quantum spin Hall effect described by the
      Kane-Mele model. The topological quantities associated with these phenomena are
      the conventional Chern number and spin Chern number, respectively. A recent
      interesting idea, time-reversal symmetry breaking via a temporary periodic
      external stimulation, is also discussed.

PMID- 27877727
TI  - Progress in the materials science of silicene.
AB  - In its freestanding, yet hypothetical form, the Si counterpart of graphene called
      silicene is predicted to possess massless Dirac fermions and to exhibit an
      experimentally accessible quantum spin Hall effect. Such interesting electronic
      properties are not realized in two-dimensional (2D) Si honeycomb lattices
      prepared recently on metallic substrates where the crystal and hybrid electronic
      structures of these 'epitaxial silicene' phases are strongly influenced by the
      substrate, and thus different from those predicted for isolated 2D structures.
      While the realization of such low-dimensional Si pi materials has hardly been
      imagined previously, it is evident that the materials science behind silicene
      remains challenging. In this contribution, we will review our recent results that
      lead to an enhanced understanding of epitaxial silicene formed on diboride thin
      films, and discuss the remaining challenges that must be addressed in order to
      turn Si 2D nanostructures into technologically interesting nanoelectronic
      materials.

PMID- 27877728
TI  - Very large thermal rectification in bulk composites consisting partly of
      icosahedral quasicrystals.
AB  - The bulk thermal rectifiers usable at a high temperature above 300 K were
      developed by making full use of the unusual electron thermal conductivity of
      icosahedral quasicrystals. The unusual electron thermal conductivity was caused
      by a synergy effect of quasiperiodicity and by a narrow pseudogap at the Fermi
      level. The rectification ratio, defined by TRR = [Formula: see text], reached
      vary large values exceeding 2.0. This significant thermal rectification would
      lead to new practical applications for the heat management.

PMID- 27877729
TI  - High-pressure synthesis, crystal structure, and magnetic properties of KSbO3-type
      5d oxides K0.84OsO3 and Bi2.93Os3O11.
AB  - 5d Solid-state oxides K0.84OsO3 (Os5.16+; 5d2.84) and Bi2.93Os3O11 (Os4.40+;
      5d3.60) were synthesized under high-pressure and high-temperature conditions (6
      GPa and 1500-1700  degrees C). Their crystal structures were determined by
      synchrotron x-ray diffraction and their 5d electronic properties and tunnel-like
      structure motifs were investigated. A KSbO3-type structure with a space group of
      Im-3 and Pn-3 was determined for K0.84OsO3 and Bi2.93Os3O11, respectively. The
      magnetic and electronic transport properties of the polycrystalline compounds
      were compared with those obtained theoretically. It was revealed that the 5d
      tunnel-like structures are paramagnetic with metallic charge conduction at
      temperatures above 2 K. This was similar to what was observed for structurally
      relevant 5d oxides, including Bi3Re3O11 (Re4.33+; 5d2.66) and Ba2Ir3O9 (Ir4.66+;
      5d4.33). The absence of long-range magnetic order seems to be common among 5d
      KSbO3-like oxides, regardless of the number of 5d electrons (between 2.6 and 4.3
      per 5d atom).

PMID- 27877730
TI  - Recent advances in understanding the reinforcing ability and mechanism of carbon
      nanotubes in ceramic matrix composites.
AB  - Since the discovery of carbon nanotubes (CNTs), commonly referred to as ultimate
      reinforcement, the main purpose for fabricating CNT-ceramic matrix composites has
      been mainly to improve the fracture toughness and strength of the ceramic matrix
      materials. However, there have been many studies reporting marginal improvements
      or even the degradation of mechanical properties. On the other hand, those
      studies claiming noticeable toughening measured using indentation, which is an
      indirect/unreliable characterization method, have not demonstrated the
      responsible mechanisms applicable to the nanoscale, flexible CNTs; instead, those
      studies proposed those classical methods applicable to microscale fiber/whisker
      reinforced ceramics without showing any convincing evidence of load transfer to
      the CNTs. Therefore, the ability of CNTs to directly improve the macroscopic
      mechanical properties of structural ceramics has been strongly questioned and
      debated in the last ten years. In order to properly discuss the reinforcing
      ability (and possible mechanisms) of CNTs in a ceramic host material, there are
      three fundamental questions to our knowledge at both the nanoscale and macroscale
      levels that need to be addressed: (1) does the intrinsic load-bearing ability of
      CNTs change when embedded in a ceramic host matrix?; (2) when there is an
      intimate atomic-level interface without any chemical reaction with the matrix,
      could one expect any load transfer to the CNTs along with effective load bearing
      by them during crack propagation?; and (3) considering their nanometer-scale
      dimensions, flexibility and radial softness, are the CNTs able to improve the
      mechanical properties of the host ceramic matrix at the macroscale when
      individually, intimately and uniformly dispersed? If so, how? Also, what is the
      effect of CNT concentration in such a defect-free composite system? Here, we
      briefly review the recent studies addressing the above fundamental questions. In
      particular, we discuss the new reinforcing mechanism at the nanoscale responsible
      for unprecedented, simultaneous mechanical improvements and highlight the
      scalable processing method enabling the fabrication of defect-free CNT
      concentered ceramics and CNT-graded composites with unprecedented properties.
      Finally, possible future directions will be briefly presented.

PMID- 27877732
TI  - Palladium nanoparticle deposition via precipitation: a new method to
      functionalize macroporous silicon.
AB  - We present an original two-step method for the deposition via precipitation of Pd
      nanoparticles into macroporous silicon. The method consists in immersing a
      macroporous silicon sample in a PdCl2/DMSO solution and then in annealing the
      sample at a high temperature. The impact of composition and concentration of the
      solution and annealing time on the nanoparticle characteristics is investigated.
      This method is compared to electroless plating, which is a standard method for
      the deposition of Pd nanoparticles. Scanning electron microscopy and computerized
      image processing are used to evaluate size, shape, surface density and deposition
      homogeneity of the Pd nanoparticles on the pore walls. Energy-dispersive x-ray
      spectroscopy (EDX) and x-ray photoelectron spectroscopy (XPS) analyses are used
      to evaluate the composition of the deposited nanoparticles. In contrast to
      electroless plating, the proposed method leads to homogeneously distributed Pd
      nanoparticles along the macropores depth with a surface density that increases
      proportionally with the PdCl2 concentration. Moreover EDX and XPS analysis showed
      that the nanoparticles are composed of Pd in its metallic state, while
      nanoparticles deposited by electroless plating are composed of both metallic Pd
      and PdO x .

PMID- 27877731
TI  - A comparison study of different physical treatments on cartilage matrix derived
      porous scaffolds for tissue engineering applications.
AB  - Native cartilage matrix derived (CMD) scaffolds from various animal and human
      sources have drawn attention in cartilage tissue engineering due to the
      demonstrable presence of bioactive components. Different chemical and physical
      treatments have been employed to enhance the micro-architecture of CMD scaffolds.
      In this study we have assessed the typical effects of physical cross-linking
      methods, namely ultraviolet (UV) light, dehydrothermal (DHT) treatment, and
      combinations of them on bovine articular CMD porous scaffolds with three
      different matrix concentrations (5%, 15% and 30%) to assess the relative
      strengths of each treatment. Our findings suggest that UV and UV-DHT treatments
      on 15% CMD scaffolds can yield architecturally optimal scaffolds for cartilage
      tissue engineering.

PMID- 27877735
TI  - Focus on materials science of topological insulators and superconductors.

PMID- 27877734
TI  - Single-step co-deposition of nanostructured tungsten oxide supported gold
      nanoparticles using a gold-phosphine cluster complex as the gold precursor.
AB  - The use of a molecular gold organometallic cluster in chemical vapour deposition
      is reported, and it is utilized, together with a tungsten oxide precursor, for
      the single-step co-deposition of (nanostructured) tungsten oxide supported gold
      nanoparticles (NPs). The deposited gold-NP and tungsten oxide supported gold-NP
      are highly active catalysts for benzyl alcohol oxidation; both show higher
      activity than SiO2 supported gold-NP synthesized via a solution-phase method, and
      tungsten oxide supported gold-NP show excellent selectivity for conversion to
      benzaldehyde.

PMID- 27877733
TI  - Superhydrophobic silica wool-a facile route to separating oil and hydrophobic
      solvents from water.
AB  - Silica microfiber wool was systematically functionalized in order to provide an
      extremely water repellent and oleophilic material. This was carried out using a
      two-step functionalization that was shown to be a highly effective method for
      generating an intense water repulsion and attraction for oil. A demonstration of
      the silica wools application is shown through the highly efficient separation of
      oils and hydrophobic solvents from water. Water is confined to the extremities of
      the material, while oil is absorbed into the voids within the wool. The effect of
      surface functionalization is monitored though observing the interaction of the
      material with both oils and water, in addition to scanning electron microscope
      images, x-ray photoelectron spectroscopy and energy dispersive x-ray analysis.
      The material can be readily utilized in many applications, including the cleaning
      of oil spills and filtering during industrial processes, as well as further water
      purification tasks-while not suffering the losses of efficiency observed in
      current leading polymeric materials.

PMID- 27877736
TI  - Nanoarchitectonics + future leaders = bright success in materials science and
      technology.

PMID- 27877737
TI  - Informatics derived materials databases for multifunctional properties.
AB  - In this review, we provide an overview of the development of quantitative
      structure-property relationships incorporating the impact of data uncertainty
      from small, limited knowledge data sets from which we rapidly develop new and
      larger databases. Unlike traditional database development, this informatics based
      approach is concurrent with the identification and discovery of the key metrics
      controlling structure-property relationships; and even more importantly we are
      now in a position to build materials databases based on design 'intent' and not
      just design parameters. This permits for example to establish materials databases
      that can be used for targeted multifunctional properties and not just one
      characteristic at a time as is presently done. This review provides a summary of
      the computational logic of building such virtual databases and gives some
      examples in the field of complex inorganic solids for scintillator applications.

PMID- 27877738
TI  - Synthesis of fullerene nanowhiskers using the liquid-liquid interfacial
      precipitation method and their mechanical, electrical and superconducting
      properties.
AB  - Fullerene nanowhiskers (FNWs) are thin crystalline fibers composed of fullerene
      molecules, including C60, C70, endohedral, or functionalized fullerenes. FNWs
      display n-type semiconducting behavior and are used in a diverse range of
      applications, including field-effect transistors, solar cells, chemical sensors,
      and photocatalysts. Alkali metal-doped C60 (fullerene) nanowhiskers (C60NWs)
      exhibit superconducting behavior. Potassium-doped C60NWs have realized the
      highest superconducting volume fraction of the alkali metal-doped C60 crystals
      and display a high critical current density (Jc) under a high magnetic field of
      50 kOe. The growth control of FNWs is important for their success in practical
      applications. This paper reviews recent FNWs research focusing on their
      mechanical, electrical and superconducting properties and growth mechanisms in
      the liquid-liquid interfacial precipitation method.

PMID- 27877739
TI  - Non-reciprocity and topology in optics: one-way road for light via surface magnon
      polariton.
AB  - We show how non-reciprocity and topology are used to construct an optical one-way
      waveguide in the Voigt geometry. First, we present a traditional approach of the
      one-way waveguide of light using surface polaritons under a static magnetic
      field. Second, we explain a recent discovery of a topological approach using
      photonic crystals with the magneto-optical coupling. Third, we present a
      combination of the two approaches, toward a broadband one-way waveguide in the
      microwave range.

PMID- 27877741
TI  - Engineering Dirac electrons emergent on the surface of a topological insulator.
AB  - The concept of the topological insulator (TI) has introduced a new point of view
      to condensed-matter physics, relating a priori unrelated subfields such as
      quantum (spin, anomalous) Hall effects, spin-orbit coupled materials, some
      classes of nodal superconductors, superfluid 3He, etc. From a technological point
      of view, TIs are expected to serve as platforms for realizing dissipationless
      transport in a non-superconducting context. The TI exhibits a gapless surface
      state with a characteristic conic dispersion (a surface Dirac cone). Here, we
      review peculiar finite-size effects applicable to such surface states in TI
      nanostructures. We highlight the specific electronic properties of TI nanowires
      and nanoparticles, and in this context we contrast the cases of weak and strong
      TIs. We study the robustness of the surface and the bulk of TIs against disorder,
      addressing the physics of Dirac and Weyl semimetals as a new research perspective
      in the field.

PMID- 27877740
TI  - Giant multiferroic effects in topological GeTe-Sb2Te3 superlattices.
AB  - Multiferroics, materials in which both magnetic and electric fields can induce
      each other, resulting in a magnetoelectric response, have been attracting
      increasing attention, although the induced magnetic susceptibility and dielectric
      constant are usually small and have typically been reported for low temperatures.
      The magnetoelectric response usually depends on d-electrons of transition metals.
      Here we report that in [(GeTe)2(Sb2Te3) l ] m superlattice films (where l and m
      are integers) with topological phase transition, strong magnetoelectric response
      may be induced at temperatures above room temperature when the external fields
      are applied normal to the film surface. By ab initio computer simulations, it is
      revealed that the multiferroic properties are induced due to the breaking of
      spatial inversion symmetry when the p-electrons of Ge atoms change their bonding
      geometry from octahedral to tetrahedral. Finally, we demonstrate the existence in
      such structures of spin memory, which paves the way for a future hybrid device
      combining nonvolatile phase-change memory and magnetic spin memory.

PMID- 27877742
TI  - A short guide to topological terms in the effective theories of condensed matter.
AB  - This article is meant as a gentle introduction to the topological terms that
      often play a decisive role in effective theories describing topological quantum
      effects in condensed matter systems. We first take up several prominent examples,
      mainly from the area of quantum magnetism and superfluids/superconductors. We
      then briefly discuss how these ideas are now finding incarnations in the studies
      of symmetry-protected topological phases, which are in a sense a generalization
      of the concept of topological insulators to a wider range of materials, including
      magnets and cold atoms.

PMID- 27877743
TI  - Synthesis and characterization of 3D topological insulators: a case TlBi(S1-x Se
      x )2.
AB  - In this article, practical methods for synthesizing Tl-based ternary III-V-VI2
      chalcogenide TlBi(S[Formula: see text]Se x )2 are described in detail, along with
      characterization by x-ray diffraction and charge transport properties. The
      TlBi(S[Formula: see text]Se x )2 system is interesting because it shows a
      topological phase transition, where a topologically nontrivial phase changes to a
      trivial phase without changing the crystal structure qualitatively. In addition,
      Dirac semimetals whose bulk band structure shows a Dirac-like dispersion are
      considered to exist near the topological phase transition. The technique shown
      here is also generally applicable for other chalcogenide topological insulators,
      and will be useful for studying topological insulators and related materials.

PMID- 27877744
TI  - Facile synthesis of alpha-Fe2O3 nanodisk with superior photocatalytic performance
      and mechanism insight.
AB  - Intrinsic short hole diffusion length is a well-known problem for alpha-Fe2O3 as
      a visible-light photocatalytic material. In this paper, a nanodisk morphology was
      designed to remarkably enhance separation of electron-hole pairs of alpha-Fe2O3.
      As expected, alpha-Fe2O3 nanodisks presented superior photocatalytic activity
      toward methylene blue degradation: more than 90% of the dye could be
      photodegraded within 30 min in comparison with a degradation efficiency of 50%
      for conventional Fe2O3 powder. The unique multilayer structure is thought to play
      a key role in the remarkably improved photocatalytic performance. Further
      experiments involving mechanism investigations revealed that instead of high
      surface area, .OH plays a crucial role in methylene blue degradation and that O.2
      may also contribute effectively to the degradation process. This paper
      demonstrates a facile and energy-saving route to fabricating homogenous alpha
      Fe2O3 nanodisks with superior photocatalytic activity that is suitable for the
      treatment of contaminated water and that meets the requirement of mass
      production.

PMID- 27877745
TI  - Nano and micro architectures for self-propelled motors.
AB  - Self-propelled micromotors are emerging as important tools that help us
      understand the fundamentals of motion at the microscale and the nanoscale.
      Development of the motors for various biomedical and environmental applications
      is being pursued. Multiple fabrication methods can be used to construct the
      geometries of different sizes of motors. Here, we present an overview of
      appropriate methods of fabrication according to both size and shape requirements
      and the concept of guiding the catalytic motors within the confines of wall.
      Micromotors have also been incorporated with biological systems for a new type of
      fabrication method for bioinspired hybrid motors using three-dimensional (3D)
      printing technology. The 3D printed hybrid and bioinspired motors can be
      propelled by using ultrasound or live cells, offering a more biocompatible
      approach when compared to traditional catalytic motors.

PMID- 27877746
TI  - N- and S-doped high surface area carbon derived from soya chunks as scalable and
      efficient electrocatalysts for oxygen reduction.
AB  - Highly stable, cost-effective electrocatalysts facilitating oxygen reduction are
      crucial for the commercialization of membrane-based fuel cell and battery
      technologies. Herein, we demonstrate that protein-rich soya chunks with a high
      content of N, S and P atoms are an excellent precursor for heteroatom-doped
      highly graphitized carbon materials. The materials are nanoporous, with a surface
      area exceeding 1000 m2 g-1, and they are tunable in doping quantities. These
      materials exhibit highly efficient catalytic performance toward oxygen reduction
      reaction (ORR) with an onset potential of -0.045 V and a half-wave potential of 
      0.211 V (versus a saturated calomel electrode) in a basic medium, which is
      comparable to commercial Pt catalysts and is better than other recently developed
      metal-free carbon-based catalysts. These exhibit complete methanol tolerance and
      a performance degradation of merely ~5% as compared to ~14% for a commercial Pt/C
      catalyst after continuous use for 3000 s at the highest reduction current. We
      found that the fraction of graphitic N increases at a higher graphitization
      temperature, leading to the near complete reduction of oxygen. It is believed
      that due to the easy availability of the precursor and the possibility of genetic
      engineering to homogeneously control the heteroatom distribution, the synthetic
      strategy is easily scalable, with further improvement in performance.

PMID- 27877747
TI  - Shape-memory surfaces for cell mechanobiology.
AB  - Shape-memory polymers (SMPs) are a new class of smart materials, which have the
      capability to change from a temporary shape 'A' to a memorized permanent shape
      'B' upon application of an external stimulus. In recent years, SMPs have
      attracted much attention from basic and fundamental research to industrial and
      practical applications due to the cheap and efficient alternative to well-known
      metallic shape-memory alloys. Since the shape-memory effect in SMPs is not
      related to a specific material property of single polymers, the control of
      nanoarchitecture of polymer networks is particularly important for the smart
      functions of SMPs. Such nanoarchitectonic approaches have enabled us to further
      create shape-memory surfaces (SMSs) with tunable surface topography at nano
      scale. The present review aims to bring together the exciting design of SMSs and
      the ever-expanding range of their uses as tools to control cell functions. The
      goal for these endeavors is to mimic the surrounding mechanical cues of
      extracellular environments which have been considered as critical parameters in
      cell fate determination. The untapped potential of SMSs makes them one of the
      most exciting interfaces of materials science and cell mechanobiology.

PMID- 27877750
TI  - Recent progress in advanced optical materials based on gadolinium aluminate
      garnet (Gd3Al5O12).
AB  - This review article summarizes the recent achievements in stabilization of the
      metastable lattice of gadolinium aluminate garnet (Gd3Al5O12, GAG) and the
      related developments of advanced optical materials, including down-conversion
      phosphors, up-conversion phosphors, transparent ceramics, and single crystals.
      Whenever possible, the materials are compared with their better known YAG and
      LuAG counterparts to demonstrate the merits of the GAG host. It is shown that
      novel emission features and significantly improved luminescence can be attained
      for a number of phosphor systems with the more covalent GAG lattice and the
      efficient energy transfer from Gd3+ to the activator. Ce3+ doped GAG-based single
      crystals and transparent ceramics are also shown to simultaneously possess the
      advantages of high theoretical density, fast scintillation decay, and high light
      yields, and hold great potential as scintillators for a wide range of
      applications. The unresolved issues are also pointed out.

PMID- 27877749
TI  - Combination of supported bimetallic rhodium-molybdenum catalyst and cerium oxide
      for hydrogenation of amide.
AB  - Hydrogenation of cyclohexanecarboxamide to aminomethylcyclohexane was conducted
      with silica-supported bimetallic catalysts composed of noble metal and group 6-7
      elements. The combination of rhodium and molybdenum with molar ratio of 1:1
      showed the highest activity. The effect of addition of various metal oxides was
      investigated on the catalysis of Rh-MoO x /SiO2, and the addition of CeO2 much
      increased the activity and selectivity. Higher hydrogen pressure and higher
      reaction temperature in the tested range of 2-8 MPa and 393-433 K, respectively,
      were favorable in view of both activity and selectivity. The highest yield of
      aminomethylcyclohexane obtained over Rh-MoO x /SiO2 + CeO2 was 63%. The effect of
      CeO2 addition was highest when CeO2 was not calcined, and CeO2 calcined at >773 K
      showed a smaller effect. The use of CeO2 as a support rather decreased the
      activity in comparison with Rh-MoO x /SiO2. The weakly-basic nature of CeO2
      additive can affect the surface structure of Rh-MoO x /SiO2, i.e. reducing the
      ratio of Mo-OH/Mo-O- sites.

PMID- 27877748
TI  - Alkyl-pi engineering in state control toward versatile optoelectronic soft
      materials.
AB  - Organic pi-conjugated molecules with extremely rich and tailorable electronic and
      optical properties are frequently utilized for the fabrication of optoelectronic
      devices. To achieve high solubility for facile solution processing and desirable
      softness for flexible device fabrication, the rigid pi units were in most cases
      attached by alkyl chains through chemical modification. Considerable numbers of
      alkylated-pi molecular systems with versatile applications have been reported.
      However, a profound understanding of the molecular state control through proper
      alkyl chain substitution is still highly demanded because effective applications
      of these molecules are closely related to their physical states. To explore the
      underlying rule, we review a large number of alkylated-pi molecules with emphasis
      on the interplay of van der Waals interactions (vdW) of the alkyl chains and pi
      pi interactions of the pi moieties. Based on our comprehensive investigations of
      the two interactions' impacts on the physical states of the molecules, a clear
      guidance for state control by alkyl-pi engineering is proposed. Specifically,
      either with proper alkyl chain substitution or favorable additives, the vdW and
      pi-pi interactions can be adjusted, resulting in modulation of the physical
      states and optoelectronic properties of the molecules. We believe the strategy
      summarized here will significantly benefit the alkyl-pi chemistry toward wide
      spread applications in optoelectronic devices.

PMID- 27877751
TI  - Probing the bulk ionic conductivity by thin film hetero-epitaxial engineering.
AB  - Highly textured thin films with small grain boundary regions can be used as model
      systems to directly measure the bulk conductivity of oxygen ion conducting
      oxides. Ionic conducting thin films and epitaxial heterostructures are also
      widely used to probe the effect of strain on the oxygen ion migration in oxide
      materials. For the purpose of these investigations a good lattice matching
      between the film and the substrate is required to promote the ordered film
      growth. Moreover, the substrate should be a good electrical insulator at high
      temperature to allow a reliable electrical characterization of the deposited
      film. Here we report the fabrication of an epitaxial heterostructure made with a
      double buffer layer of BaZrO3 and SrTiO3 grown on MgO substrates that fulfills
      both requirements. Based on such template platform, highly ordered (001)
      epitaxially oriented thin films of 15% Sm-doped CeO2 and 8 mol% Y2O3 stabilized
      ZrO2 are grown. Bulk conductivities as well as activation energies are measured
      for both materials, confirming the success of the approach. The reported
      insulating template platform promises potential application also for the
      electrical characterization of other novel electrolyte materials that still need
      a thorough understanding of their ionic conductivity.

PMID- 27877752
TI  - Dynamic probe of ZnTe(110) surface by scanning tunneling microscopy.
AB  - The reconstructed surface structure of the II-VI semiconductor ZnTe (110), which
      is a promising material in the research field of semiconductor spintronics, was
      studied by scanning tunneling microscopy/spectroscopy (STM/STS). First, the
      surface states formed by reconstruction by the charge transfer of dangling bond
      electrons from cationic Zn to anionic Te atoms, which are similar to those of IV
      and III-V semiconductors, were confirmed in real space. Secondly, oscillation in
      tunneling current between binary states, which is considered to reflect a
      conformational change in the topmost Zn-Te structure between the reconstructed
      and bulk-like ideal structures, was directly observed by STM. Third, using the
      technique of charge injection, a surface atomic structure was successfully
      fabricated, suggesting the possibility of atomic-scale manipulation of this
      widely applicable surface of ZnTe.

PMID- 27877754
TI  - Highly efficient in vitro biosynthesis of silver nanoparticles using
      Lysinibacillus sphaericus MR-1 and their characterization.
AB  - Silver nanoparticles (AgNPs) have been widely used in diverse fields due to their
      superior properties. Currently the biosynthesis of AgNPs is in the limelight of
      modern nanotechnology because of its green properties. However, relatively low
      yield and inefficiency diminish the prospect of applying these biosynthesized
      AgNPs. In this work, a rapid mass AgNP biosynthesis method using the cell-free
      extract of a novel bacterial strain, Lysinibacillus sphaericus MR-1, which has
      been isolated from a chemical fertilizer plant, is reported. In addition, the
      optimum synthesis conditions of AgNPs were investigated. The optimum pH,
      temperature, dosage, and reaction time were 12, 70  degrees C, 20 mM AgNO3, and
      75 min, respectively. Finally, AgNPs were characterized by optical absorption
      spectroscopy, zeta potential and size distribution analysis, x-ray diffraction,
      electron microscopy, and energy-dispersive x-ray spectroscopy. The results
      revealed that these biosynthesized AgNPs were bimolecular covered, stable, well
      dispersed face centered cubic (fcc) spherical crystalline particles with
      diameters in the range 5-20 nm. The advantages of this approach are its
      simplicity, high efficiency, and eco-friendly and cost-effective features.

PMID- 27877753
TI  - Highly elastic conductive polymeric MEMS.
AB  - Polymeric structures with integrated, functional microelectrical mechanical
      systems (MEMS) elements are increasingly important in various applications such
      as biomedical systems or wearable smart devices. These applications require
      highly flexible and elastic polymers with good conductivity, which can be
      embedded into a matrix that undergoes large deformations. Conductive
      polydimethylsiloxane (PDMS) is a suitable candidate but is still challenging to
      fabricate. Conductivity is achieved by filling a nonconductive PDMS matrix with
      conductive particles. In this work, we present an approach that uses new mixing
      techniques to fabricate conductive PDMS with different fillers such as carbon
      black, silver particles, and multiwalled carbon nanotubes. Additionally, the
      electrical properties of all three composites are examined under continuous
      mechanical stress. Furthermore, we present a novel, low-cost, simple three-step
      molding process that transfers a micro patterned silicon master into a
      polystyrene (PS) polytetrafluoroethylene (PTFE) replica with improved release
      features. This PS/PTFE mold is used for subsequent structuring of conductive PDMS
      with high accuracy. The non sticking characteristics enable the fabrication of
      delicate structures using a very soft PDMS, which is usually hard to release from
      conventional molds. Moreover, the process can also be applied to polyurethanes
      and various other material combinations.

PMID- 27877755
TI  - Active vacuum brazing of CNT films to metal substrates for superior electron
      field emission performance.
AB  - The joining of macroscopic films of vertically aligned multiwalled carbon
      nanotubes (CNTs) to titanium substrates is demonstrated by active vacuum brazing
      at 820  degrees C with a Ag-Cu-Ti alloy and at 880  degrees C with a Cu-Sn-Ti-Zr
      alloy. The brazing methodology was elaborated in order to enable the production
      of highly electrically and thermally conductive CNT/metal substrate contacts. The
      interfacial electrical resistances of the joints were measured to be as low as
      0.35 Omega. The improved interfacial transport properties in the brazed films
      lead to superior electron field-emission properties when compared to the as-grown
      films. An emission current of 150 MUA was drawn from the brazed nanotubes at an
      applied electric field of 0.6 V MUm-1. The improvement in electron field-emission
      is mainly attributed to the reduction of the contact resistance between the
      nanotubes and the substrate. The joints have high re-melting temperatures up to
      the solidus temperatures of the alloys; far greater than what is achievable with
      standard solders, thus expanding the application potential of CNT films to high
      current and high-power applications where substantial frictional or resistive
      heating is expected.

PMID- 27877756
TI  - Facile preparation of core@shell and concentration-gradient spinel particles for
      Li-ion battery cathode materials.
AB  - Core@shell and concentration-gradient particles have attracted much attention as
      improved cathodes for Li-ion batteries (LIBs). However, most of their preparation
      routes have employed a precisely-controlled co-precipitation method. Here, we
      report a facile preparation route of core@shell and concentration-gradient spinel
      particles by dry powder processing. The core@shell particles composed of the MnO2
      core and the Li(Ni,Mn)2O4 spinel shell are prepared by mechanical treatment using
      an attrition-type mill, whereas the concentration-gradient spinel particles with
      an average composition of LiNi0.32Mn1.68O4 are produced by calcination of their
      core@shell particles as a precursor. The concentration-gradient LiNi0.32Mn1.68O4
      spinel cathode exhibits the high discharge capacity of 135.3 mA h g-1, the wide
      range plateau at a high voltage of 4.7 V and the cyclability with a capacity
      retention of 99.4% after 20 cycles. Thus, the facile preparation route of the
      core@shell and concentration-gradient particles may provide a new opportunity for
      the discovery and investigation of functional materials as well as for the
      cathode materials for LIBs.

PMID- 27877757
TI  - Low temperature and cost-effective growth of vertically aligned carbon nanofibers
      using spin-coated polymer-stabilized palladium nanocatalysts.
AB  - We describe a fast and cost-effective process for the growth of carbon nanofibers
      (CNFs) at a temperature compatible with complementary metal oxide semiconductor
      technology, using highly stable polymer-Pd nanohybrid colloidal solutions of
      palladium catalyst nanoparticles (NPs). Two polymer-Pd nanohybrids, namely
      poly(lauryl methacrylate)-block-poly((2-acetoacetoxy)ethyl methacrylate)/Pd
      (LauMA x -b-AEMA y /Pd) and polyvinylpyrrolidone/Pd were prepared in organic
      solvents and spin-coated onto silicon substrates. Subsequently, vertically
      aligned CNFs were grown on these NPs by plasma enhanced chemical vapor deposition
      at different temperatures. The electrical properties of the grown CNFs were
      evaluated using an electrochemical method, commonly used for the characterization
      of supercapacitors. The results show that the polymer-Pd nanohybrid solutions
      offer the optimum size range of palladium catalyst NPs enabling the growth of
      CNFs at temperatures as low as 350  degrees C. Furthermore, the CNFs grown at
      such a low temperature are vertically aligned similar to the CNFs grown at 550 
      degrees C. Finally the capacitive behavior of these CNFs was similar to that of
      the CNFs grown at high temperature assuring the same electrical properties thus
      enabling their usage in different applications such as on-chip capacitors,
      interconnects, thermal heat sink and energy storage solutions.

PMID- 27877759
TI  - Focus on properties and applications of perovskites.

PMID- 27877758
TI  - High-sensitivity piezoelectric perovskites for magnetoelectric composites.
AB  - A highly topical set of perovskite oxides are high-sensitivity piezoelectric
      ones, among which Pb(Zr,Ti)O3 at the morphotropic phase boundary (MPB) between
      ferroelectric rhombohedral and tetragonal polymorphic phases is reckoned a case
      study. Piezoelectric ceramics are used in a wide range of mature,
      electromechanical transduction technologies like piezoelectric sensors, actuators
      and ultrasound generation, to name only a few examples, and more recently for
      demonstrating novel applications like magnetoelectric composites. In this case,
      piezoelectric perovskites are combined with magnetostrictive materials to provide
      magnetoelectricity as a product property of the piezoelectricity and
      piezomagnetism of the component phases. Interfaces play a key issue, for they
      control the mechanical coupling between the piezoresponsive phases. We present
      here main results of our investigation on the suitability of the high sensitivity
      MPB piezoelectric perovskite BiScO3-PbTiO3 in combination with ferrimagnetic
      spinel oxides for magnetoelectric composites. Emphasis has been put on the
      processing at low temperature to control reactions and interdiffusion between the
      two oxides. The role of the grain size effects is extensively addressed.

PMID- 27877760
TI  - Focus on advanced inorganic materials science: non-traditional concepts and
      approaches.

PMID- 27877762
TI  - Structure and cation distribution in perovskites with small cations at the A
      site: the case of ScCoO3.
AB  - We synthesize ScCoO3 perovskite and its solid solutions, ScCo1-x Fe x O3 and
      ScCo1-x Cr x O3, under high pressure (6 GPa) and high temperature (1570 K)
      conditions. We find noticeable shifts from the stoichiometric compositions,
      expressed as (Sc1-xMx )MO3 with x = 0.05-0.11 and M = Co, (Co, Fe) and (Co, Cr).
      The crystal structure of (Sc0.95Co0.05)CoO3 is refined using synchrotron x-ray
      powder diffraction data: space group Pnma (No. 62), Z = 4 and lattice parameters
      a = 5.26766(1) A, b = 7.14027(2) A and c = 4.92231(1) A. (Sc0.95Co0.05)CoO3
      crystallizes in the GdFeO3-type structure similar to other members of the
      perovskite cobaltite family, ACoO3 (A3+ = Y and Pr-Lu). There is evidence that
      (Sc0.95Co0.05)CoO3 has non-magnetic low-spin Co3+ ions at the B site and
      paramagnetic high-spin Co3+ ions at the A site. In the iron-doped samples (Sc1
      xMx )MO3 with M = (Co, Fe), Fe3+ ions have a strong preference to occupy the A
      site of such perovskites at small doping levels.

PMID- 27877764
TI  - Photoluminescent lead(II) coordination polymers stabilised by bifunctional
      organoarsonate ligands.
AB  - Four lead(II) coordination polymers were isolated under hydro(solvo)thermal
      conditions. The applied synthetic methodology takes advantage of the coordination
      behaviour of a new bifunctional organoarsonate ligand, 4-(1, 2, 4-triazol-4
      yl)phenylarsonic acid (H2TPAA) and involves the variation of lead(II) reactants,
      metal/ligand mole ratios, and solvents. The constitutional composition of the
      four lead(II) coordination polymers can be formulated as
      [Pb2(TPAA)(HTPAA)(NO3)].6H2O (1), [Pb2(TPAA)(HTPAA)2].DMF.0.5H2O (DMF = N, N
      Dimethylformamide) (2), [Pb2Cl2(TPAA)H2O] (3), and [Pb3Cl(TPAA)(HTPAA)2H2O]Cl
      (4). The compounds were characterized by single-crystal and powder x-ray
      diffraction techniques, thermogravimetric analyses, infra-red spectroscopy, and
      elemental analyses. Single-crystal x-ray diffraction reveals that 1 and 2
      represent two-dimensional (2D) layered structures whilst 3 and 4 form three
      dimensional (3D) frameworks. The structures of 1, 2, and 4 contain one
      dimensional (1D) {PbII/AsO3} substructures, while 3 is composed of 2D {PbII/AsO3}
      arrays. Besides their interesting topologies, 1-4 all exhibit photoluminescence
      properties in the solid state at room temperature.

PMID- 27877765
TI  - Preparation of a platinum electrocatalyst by coaxial pulse arc plasma deposition.
AB  - We have developed a new method of preparing Pt electrocatalysts through a dry
      process. By coaxial pulse arc plasma deposition (CAPD), highly ionized metal
      plasma can be generated from a target rod without any discharged gases, and Pt
      nanoparticles can be deposited on a carbon support. The small-sized Pt
      nanoparticles are distributed over the entire carbon surface. From transmission
      electron microscopy (TEM), the average size of the deposited Pt nanoparticles is
      estimated to be 2.5 nm, and their size distribution is narrow. Our
      electrocatalyst shows considerably improved catalytic activity and stability
      toward methanol oxidation reaction (MOR) compared with commercially available Pt
      catalysts such as Pt black and Pt/carbon (PtC). Inspired by its very high
      efficiency toward MOR, we also measured the catalytic performance for oxygen
      reduction reaction (ORR). Our PtC catalyst shows a better performance with half
      wave potential of 0.87 V, which is higher than those of commercially available Pt
      catalysts. The higher performance is also supported by a right-shifted onset
      potential. Our preparation is simple and could be applied to other metallic
      nanocrystals as a novel platform in catalysis, fuel cells and biosensors.

PMID- 27877763
TI  - Non-covalent polymer wrapping of carbon nanotubes and the role of wrapped
      polymers as functional dispersants.
AB  - Carbon nanotubes (CNTs) have been recognized as a promising material in a wide
      range of applications from biotechnology to energy-related devices. However, the
      poor solubility in aqueous and organic solvents hindered the applications of
      CNTs. As studies have progressed, the methodology for CNT dispersion was
      established. In this methodology, the key issue is to covalently or non
      covalently functionalize the surfaces of the CNTs with a dispersant. Among the
      various types of dispersions, polymer wrapping through non-covalent interactions
      is attractive in terms of the stability and homogeneity of the functionalization.
      Recently, by taking advantage of their stability, the wrapped-polymers have been
      utilized to support and/or reinforce the unique functionality of the CNTs,
      leading to the development of high-performance devices. In this review, various
      polymer wrapping approaches, together with the applications of the polymer
      wrapped CNTs, are summarized.

PMID- 27877768
TI  - Effects of SO2 on selective catalytic reduction of NO with NH3 over a TiO2
      photocatalyst.
AB  - The effect of SO2 gas was investigated on the activity of the photo-assisted
      selective catalytic reduction of nitrogen monoxide (NO) with ammonia (NH3) over a
      TiO2 photocatalyst in the presence of excess oxygen (photo-SCR). The introduction
      of SO2 (300 ppm) greatly decreased the activity of the photo-SCR at 373 K. The
      increment of the reaction temperature enhanced the resistance to SO2 gas, and at
      553 K the conversion of NO was stable for at least 300 min of the reaction. X-ray
      diffraction, FTIR spectroscopy, thermogravimetry and differential thermal
      analysis, x-ray photoelectron spectroscopy (XPS), elemental analysis and N2
      adsorption measurement revealed that the ammonium sulfate species were generated
      after the reaction. There was a strong negative correlation between the
      deposition amount of the ammonium sulfate species and the specific surface area.
      Based on the above relationship, we concluded that the deposition of the ammonium
      sulfate species decreased the specific surface area by plugging the pore
      structure of the catalyst, and the decrease of the specific surface area resulted
      in the deactivation of the catalyst.

PMID- 27877766
TI  - Controllable assembly of silver nanoparticles induced by femtosecond laser direct
      writing.
AB  - We report controllable assembly of silver nanoparticles (Ag NPs) for patterning
      of silver microstructures. The assembly is induced by femtosecond laser direct
      writing (FsLDW). A tightly focused femtosecond laser beam is capable of trapping
      and driving Ag NPs to form desired micropatterns with a high resolution of ~190
      nm. Taking advantage of the 'direct writing' feature, three microelectrodes have
      been integrated with a microfluidic chip; two silver-based microdevices including
      a microheater and a catalytic reactor have been fabricated inside a microfluidic
      channel for chip functionalization. The FsLDW-induced programmable assembly of Ag
      NPs may open up a new way to the designable patterning of silver microstructures
      toward flexible fabrication and integration of functional devices.

PMID- 27877767
TI  - Quick high-temperature hydrothermal synthesis of mesoporous materials with 3D
      cubic structure for the adsorption of lysozyme.
AB  - Three-dimensional cage-like mesoporous FDU-12 materials with large tuneable pore
      sizes ranging from 9.9 to 15.6 nm were prepared by varying the synthesis
      temperature from 100 to 200  degrees C for the aging time of just 2 h using a tri
      block copolymer F-127(EO106PO70EO106) as the surfactant and 1,3,5-trimethyl
      benzene as the swelling agent in an acidic condition. The mesoporous structure
      and textural features of FDU-12-HX (where H denotes the hydrothermal method and X
      denotes the synthesis temperature) samples were elucidated and probed using x-ray
      diffraction, N2 adsorption, 29Si magic angle spinning nuclear magnetic resonance,
      scanning electron microscopy and transmission electron microscopy. It has been
      demonstrated that the aging time can be significantly reduced from 72 to 2 h
      without affecting the structural order of the FDU-12 materials with a simple
      adjustment of the synthesis temperature from 100 to 200  degrees C. Among the
      materials prepared, the samples prepared at 200  degrees C had the highest pore
      volume and the largest pore diameter. Lysozyme adsorption experiments were
      conducted over FDU-12 samples prepared at different temperatures in order to
      understand their biomolecule adsorption capacity, where the FDU-12-HX samples
      displayed high adsorption performance of 29 MUmol g-1 in spite of shortening the
      actual synthesis time from 72 to 2 h. Further, the influence of surface area,
      pore volume and pore diameter on the adsorption capacity of FDU-12-HX samples has
      been investigated and results are discussed in correlation with the textural
      parameters of the FDU-12-HX and other mesoporous adsorbents including SBA-15, MCM
      41, KIT-5, KIT-6 and CMK-3.

PMID- 27877769
TI  - Wurtzite-derived ternary I-III-O2 semiconductors.
AB  - Ternary zincblende-derived I-III-VI2 chalcogenide and II-IV-V2 pnictide
      semiconductors have been widely studied and some have been put to practical use.
      In contrast to the extensive research on these semiconductors, previous studies
      into ternary I-III-O2 oxide semiconductors with a wurtzite-derived beta-NaFeO2
      structure are limited. Wurtzite-derived beta-LiGaO2 and beta-AgGaO2 form alloys
      with ZnO and the band gap of ZnO can be controlled to include the visible and
      ultraviolet regions. beta-CuGaO2, which has a direct band gap of 1.47 eV, has
      been proposed for use as a light absorber in thin film solar cells. These ternary
      oxides may thus allow new applications for oxide semiconductors. However,
      information about wurtzite-derived ternary I-III-O2 semiconductors is still
      limited. In this paper we review previous studies on beta-LiGaO2, beta-AgGaO2 and
      beta-CuGaO2 to determine guiding principles for the development of wurtzite
      derived I-III-O2 semiconductors.

PMID- 27877761
TI  - Recent progress on magnetic iron oxide nanoparticles: synthesis, surface
      functional strategies and biomedical applications.
AB  - This review focuses on the recent development and various strategies in the
      preparation, microstructure, and magnetic properties of bare and surface
      functionalized iron oxide nanoparticles (IONPs); their corresponding biological
      application was also discussed. In order to implement the practical in vivo or in
      vitro applications, the IONPs must have combined properties of high magnetic
      saturation, stability, biocompatibility, and interactive functions at the
      surface. Moreover, the surface of IONPs could be modified by organic materials or
      inorganic materials, such as polymers, biomolecules, silica, metals, etc. The new
      functionalized strategies, problems and major challenges, along with the current
      directions for the synthesis, surface functionalization and bioapplication of
      IONPs, are considered. Finally, some future trends and the prospects in these
      research areas are also discussed.

PMID- 27877771
TI  - Planar silver nanowire, carbon nanotube and PEDOT:PSS nanocomposite transparent
      electrodes.
AB  - Highly conductive, transparent and flexible planar electrodes were fabricated
      using interwoven silver nanowires and single-walled carbon nanotubes (AgNW:SWCNT)
      in a PEDOT:PSS matrix via an epoxy transfer method from a silicon template. The
      planar electrodes achieved a sheet resistance of 6.6 +/- 0.0 Omega/? and an
      average transmission of 86% between 400 and 800 nm. A high figure of merit of 367
      Omega-1 is reported for the electrodes, which is much higher than that measured
      for indium tin oxide and reported for other AgNW composites. The
      AgNW:SWCNT:PEDOT:PSS electrode was used to fabricate low temperature (annealing
      free) devices demonstrating their potential to function with a range of organic
      semiconducting polymer:fullerene bulk heterojunction blend systems.

PMID- 27877770
TI  - Anisotropic multi-step etching for large-area fabrication of surface
      microstructures on stainless steel to control thermal radiation.
AB  - Controlling the thermal radiation spectra of materials is one of the promising
      ways to advance energy system efficiency. It is well known that the thermal
      radiation spectrum can be controlled through the introduction of periodic surface
      microstructures. Herein, a method for the large-area fabrication of periodic
      microstructures based on multi-step wet etching is described. The method consists
      of three main steps, i.e., resist mask fabrication via photolithography,
      electrochemical wet etching, and side wall protection. Using this method, high
      aspect micro-holes (0.82 aspect ratio) arrayed with hexagonal symmetry were
      fabricated on a stainless steel substrate. The conventional wet etching process
      method typically provides an aspect ratio of 0.3. The optical absorption peak
      attributed to the fabricated micro-hole array appeared at 0.8 MUm, and the peak
      absorbance exceeded 0.8 for the micro-holes with a 0.82 aspect ratio. While argon
      plasma etching in a vacuum chamber was used in the present study for the
      formation of the protective layer, atmospheric plasma etching should be possible
      and will expand the applicability of this new method for the large-area
      fabrication of high-aspect materials.

PMID- 27877773
TI  - Preferred growth orientation and microsegregation behaviors of eutectic in a
      nickel-based single-crystal superalloy.
AB  - A nickel-based single-crystal superalloy was employed to investigate the
      preferred growth orientation behavior of the (gamma + gamma') eutectic and the
      effect of these orientations on the segregation behavior. A novel solidification
      model for the eutectic island was proposed. At the beginning of the eutectic
      island's crystallization, the core directly formed from the liquid by the
      eutectic reaction, and then preferably grew along [100] direction. The
      crystallization of the eutectic along [110] always lagged behind that in [100]
      direction. The eutectic growth in [100] direction terminated on impinging the
      edge of the dendrites or another eutectic island. The end of the eutectic
      island's solidification terminates due to the encroachment of the eutectic
      liquid/solid interface at the dendrites or another eutectic island in [110]
      direction. The distribution of the alloying elements depended on the crystalline
      axis. The degree of the alloying elements' segregation was lower along [100] than
      [110] direction with increasing distance from the eutectic island's center.

PMID- 27877772
TI  - Preparation of macroporous zirconia monoliths from ionic precursors via an
      epoxide-mediated sol-gel process accompanied by phase separation.
AB  - Monolithic macroporous zirconia (ZrO2) derived from ionic precursors has been
      successfully fabricated via the epoxide-mediated sol-gel route accompanied by
      phase separation in the presence of propylene oxide (PO) and poly(ethylene oxide)
      (PEO). The addition of PO used as an acid scavenger mediates the gelation,
      whereas PEO enhances the polymerization-induced phase separation. The appropriate
      choice of the starting compositions allows the production of a macroporous
      zirconia monolith with a porosity of 52.9% and a Brunauer-Emmett-Teller (BET)
      surface area of 171.9 m2 . g-1. The resultant dried gel is amorphous, whereas
      tetragonal ZrO2 and monoclinic ZrO2 are precipitated at 400 and 600  degrees C,
      respectively, without spoiling the macroporous morphology. After solvothermal
      treatment with an ethanol solution of ammonia, tetragonal ZrO2 monoliths with
      smooth skeletons and well-defined mesopores can be obtained, and the BET surface
      area is enhanced to 583.8 m2 . g-1.

PMID- 27877774
TI  - Long-term aging of Ag/a-C:H:O nanocomposite coatings in air and in aqueous
      environment.
AB  - Nanocomposite coatings of silver particles embedded in a plasma polymer matrix
      possess interesting properties depending on their microstructure. The film
      microstructure is affected among others also by the RF power supplied during the
      deposition, as shown by transmission electron microscopy. The optical properties
      are characterized by UV-vis-NIR spectroscopy. An anomalous optical absorption
      peak from the Ag nanoparticles is observed and related to the microstructure of
      the nanocomposite films. Furthermore, a long-term aging of the coatings is
      studied in-depth in ambient air and in aqueous environments. It is shown that the
      studied films are not entirely stable. The deposition conditions and the
      microstructure of the films affect the processes taking place during their aging
      in both environments.

PMID- 27877775
TI  - Novel PEPA-functionalized graphene oxide for fire safety enhancement of
      polypropylene.
AB  - Polypropylene (PP) is a general-purpose plastic, but some applications are
      constrained by its high flammability. Thus, flame retardant PP is urgently
      demanded. In this article, intumescent flame retardant PP (IFRPP) composites with
      enhanced fire safety were prepared using 1-oxo-4-hydroxymethyl-2,6,7-trioxa-1
      phosphabicyclo [2.2.2] octane (PEPA) functionalized graphene oxide (PGO) as
      synergist. The PGO was prepared through a mild chemical reaction by the covalent
      attachment of a caged-structure organic compound, PEPA, onto GO nanosheets using
      toluene diisocynate (TDI) as the intermediary agent. The novel PEPA
      functionalized graphene oxide not only improves the heat resistance of GO but
      also converts GO and PEPA from hydrophobic to hydrophilic materials, which leads
      to even distribution in PP. In our case, 7 wt% addition of PGO as one of the
      fillers for IFRPP composites significantly reduces its inflammability and fire
      hazards when compared with PEPA, by the improvement of first release rate peak
      (PHRR), total heat release, first smoke release rate peak (PSRR) and total smoke
      release, suggesting its great potential as the IFR synergist in industry. The
      reason is mainly attributed to the barrier effect of the unburned graphene
      sheets, which protects by the decomposition products of PEPA and TDI, promotes
      the formation of graphitized carbon and inhibits the heat and gas release.

PMID- 27877776
TI  - Energy dispersive x-ray spectroscopy for nanostructured thin film density
      evaluation.
AB  - In this paper, we report on two fast and non-destructive methods for
      nanostructured film density evaluation based on a combination of energy
      dispersive x-ray spectroscopy for areal density measurement and scanning electron
      microscopy (SEM) for thickness evaluation. These techniques have been applied to
      films with density ranging from the density of a solid down to a few [Formula:
      see text], with different compositions and morphologies. The high resolution of
      an electron microprobe has been exploited to characterize non-uniform films both
      at the macroscopic scale and at the microscopic scale.

PMID- 27877777
TI  - Improved compaction of ZnO nano-powder triggered by the presence of acetate and
      its effect on sintering.
AB  - The retention of nanocrystallinity in dense ceramic materials is still a
      challenge, even with the application of external pressure during sintering. The
      compaction behavior of high purity and acetate enriched zinc oxide (ZnO) nano
      powders was investigated. It was found that acetate in combination with water
      plays a key role during the compaction into green bodies at moderate
      temperatures. Application of constant pressure resulted in a homogeneous green
      body with superior packing density (86% of theoretical value) at moderate
      temperature (85  degrees C) in the presence of water. In contrast, no improvement
      in density could be achieved if pure ZnO powder was used. This compaction
      behavior offers superior packing of the particles, resulting in a high relative
      density of the consolidated compact with negligible coarsening. Dissolution
      accompanying creep diffusion based matter transport is suggested to strongly
      support reorientation of ZnO particles towards densities beyond the theoretical
      limit for packing of ideal monosized spheres. Finally, the sintering trajectory
      reveals that grain growth is retarded compared to conventional processing up to
      90% of theoretical density. Moreover, nearly no radial shrinkage was observed
      after sinter-forging for bodies performed with this advanced processing method.

PMID- 27877778
TI  - Electronic conduction in La-based perovskite-type oxides.
AB  - A systematic study of La-based perovskite-type oxides from the viewpoint of their
      electronic conduction properties was performed. LaCo0.5Ni0.5O3+/-delta was found
      to be a promising candidate as a replacement for standard metals used in oxide
      electrodes and wiring that are operated at temperatures up to 1173 K in air
      because of its high electrical conductivity and stability at high temperatures.
      LaCo0.5Ni0.5O3+/-delta exhibits a high conductivity of 1.9 * 103 S cm-1 at room
      temperature (R.T.) because of a high carrier concentration n of 2.2 * 1022 cm-3
      and a small effective mass m* of 0.10 me. Notably, LaCo0.5Ni0.5O3+/-delta
      exhibits this high electrical conductivity from R.T. to 1173 K, and little change
      in the oxygen content occurs under these conditions. LaCo0.5Ni0.5O3+/-delta is
      the most suitable for the fabrication of oxide electrodes and wiring, though La1
      x Sr x CoO3+/-delta and La1-x Sr x MnO3+/-delta also exhibit high electronic
      conductivity at R.T., with maximum electrical conductivities of 4.4 * 103 S cm-1
      for La0.5Sr0.5CoO3+/-delta and 1.5 * 103 S cm-1 for La0.6Sr0.4MnO3+/-delta
      because oxygen release occurs in La1-x Sr x CoO3+/-delta as elevating temperature
      and the electrical conductivity of La0.6Sr0.4MnO3+/-delta slightly decreases at
      temperatures above 400 K.

PMID- 27877779
TI  - Concurrent bandgap narrowing and polarization enhancement in epitaxial
      ferroelectric nanofilms.
AB  - Perovskite-type ferroelectric (FE) crystals are wide bandgap materials with
      technologically valuable optical and photoelectric properties. Here, versatile
      engineering of electronic transitions is demonstrated in FE nanofilms of KTaO3,
      KNbO3 (KNO), and NaNbO3 (NNO) with a thickness of 10-30 unit cells. Control of
      the bandgap is achieved using heteroepitaxial growth of new structural phases on
      SrTiO3 (001) substrates. Compared to bulk crystals, anomalous bandgap narrowing
      is obtained in the FE state of KNO and NNO films. This effect opposes
      polarization-induced bandgap widening, which is typically found for FE materials.
      Transmission electron microscopy and spectroscopic ellipsometry measurements
      indicate that the formation of higher-symmetry structural phases of KNO and NNO
      produces the desirable red shift of the absorption spectrum towards visible
      light, while simultaneously stabilizing robust FE order. Tuning of optical
      properties in FE films is of interest for nanoscale photonic and optoelectronic
      devices.

PMID- 27877780
TI  - Magnetic properties of solid solutions between BiCrO3 and BiGaO3 with perovskite
      structures.
AB  - Magnetic properties of BiCr1-x Ga x O3 perovskite-type solid solutions are
      reported, and a magnetic phase diagram is established. As-synthesized BiCrO3 and
      BiCr0.9Ga0.1O3 crystallize in a monoclinic (m) C2/c structure. The Neel
      temperature (TN) decreases from 111 K in BiCrO3 to 98 K in BiCr0.9Ga0.1O3, and
      spin-reorientation transition temperature increases from 72 K in BiCrO3 to 83 K
      in BiCr0.9Ga0.1O3. o-BiCr0.9Ga0.1O3 with a PbZrO3-type orthorhombic structure is
      obtained by heating m-BiCr0.9Ga0.1O3 up to 573 K in air; it shows similar
      magnetic properties with those of m-BiCr0.9Ga0.1O3. TN of BiCr0.8Ga0.2O3 is 81 K,
      and TN of BiCr0.7Ga0.3O3 is 63 K. Samples with x = 0.4, 0.5, 0.6 and 0.7
      crystallize in a polar R3c structure. Long-range antiferromagnetic order with
      weak ferromagnetism is observed below TN = 56 K in BiCr0.6Ga0.4O3, TN = 36 K in
      BiCr0.5Ga0.5O3 and TN = 18 K in BiCr0.4Ga0.6O3. BiCr0.3Ga0.7O3 shows a
      paramagnetic behaviour because the Cr concentration is below the percolation
      threshold of 31%.

PMID- 27877781
TI  - Focus on materials challenges for protection - environment and health.

PMID- 27877782
TI  - Blue phase liquid crystal: strategies for phase stabilization and device
      development.
AB  - The blue phase liquid crystal (BPLC) is a highly ordered liquid crystal (LC)
      phase found very close to the LC-isotropic transition. The BPLC has demonstrated
      potential in next-generation display and photonic technology due to its
      exceptional properties such as sub-millisecond response time and wide viewing
      angle. However, BPLC is stable in a very small temperature range (0.5-1  degrees
      C) and its driving voltage is very high (~100 V). To overcome these challenges
      recent research has focused on solutions which incorporate polymers or
      nanoparticles into the blue phase to widen the temperature range from around few 
      degrees C to potentially more than 60  degrees C. In order to reduce the driving
      voltage, strategies have been attempted by modifying the device structure by
      introducing protrusion or corrugated electrodes and vertical field switching
      mechanism has been proposed. In this paper the effectiveness of the proposed
      solution will be discussed, in order to assess the potential of BPLC in display
      technology and beyond.

PMID- 27877783
TI  - A review on powder-based additive manufacturing for tissue engineering: selective
      laser sintering and inkjet 3D printing.
AB  - Since most starting materials for tissue engineering are in powder form, using
      powder-based additive manufacturing methods is attractive and practical. The
      principal point of employing additive manufacturing (AM) systems is to fabricate
      parts with arbitrary geometrical complexity with relatively minimal tooling cost
      and time. Selective laser sintering (SLS) and inkjet 3D printing (3DP) are two
      powerful and versatile AM techniques which are applicable to powder-based
      material systems. Hence, the latest state of knowledge available on the use of AM
      powder-based techniques in tissue engineering and their effect on mechanical and
      biological properties of fabricated tissues and scaffolds must be updated.
      Determining the effective setup of parameters, developing improved
      biocompatible/bioactive materials, and improving the mechanical/biological
      properties of laser sintered and 3D printed tissues are the three main concerns
      which have been investigated in this article.

PMID- 27877786
TI  - Influence of nanoparticle addition on the formation and growth of intermetallic
      compounds (IMCs) in Cu/Sn-Ag-Cu/Cu solder joint during different thermal
      conditions.
AB  - Nanocomposite lead-free solders are gaining prominence as replacements for
      conventional lead-free solders such as Sn-Ag-Cu solder in the electronic
      packaging industry. They are fabricated by adding nanoparticles such as metallic
      and ceramic particles into conventional lead-free solder. It is reported that the
      addition of such nanoparticles could strengthen the solder matrix, refine the
      intermetallic compounds (IMCs) formed and suppress the growth of IMCs when the
      joint is subjected to different thermal conditions such as thermal aging and
      thermal cycling. In this paper, we first review the fundamental studies on the
      formation and growth of IMCs in lead-free solder joints. Subsequently, we discuss
      the effect of the addition of nanoparticles on IMC formation and their growth
      under several thermal conditions. Finally, an outlook on the future growth of
      research in the fabrication of nanocomposite solder is provided.

PMID- 27877785
TI  - Tangible nanocomposites with diverse properties for heart valve application.
AB  - Cardiovascular disease claims millions of lives every year throughout the world.
      Biomaterials are used widely for the treatment of this fatal disease. With the
      advent of nanotechnology, the use of nanocomposites has become almost inevitable
      in the field of biomaterials. The versatile properties of nanocomposites, such as
      improved durability and biocompatibility, make them an ideal choice for various
      biomedical applications. Among the various nanocomposites, polyhedral oligomeric
      silsesquioxane-poly(carbonate-urea)urethane, bacterial cellulose with polyvinyl
      alcohol, carbon nanotubes, graphene oxide and nano-hydroxyapatite nanocomposites
      have gained popularity as putative choices for biomaterials in cardiovascular
      applications owing to their superior properties. In this review, various studies
      performed utilizing these nanocomposites for improving the mechanical strength,
      anti-calcification potential and hemocompatibility of heart valves are reviewed
      and summarized. The primary motive of this work is to shed light on the emerging
      nanocomposites for heart valve applications. Furthermore, we aim to promote the
      prospects of these nanocomposites in the campaign against cardiovascular
      diseases.

PMID- 27877787
TI  - Recent progress in oxynitride photocatalysts for visible-light-driven water
      splitting.
AB  - Photocatalytic water splitting into hydrogen and oxygen is a method to directly
      convert light energy into storable chemical energy, and has received considerable
      attention for use in large-scale solar energy utilization. Particulate
      semiconductors are generally used as photocatalysts, and semiconductor properties
      such as bandgap, band positions, and photocarrier mobility can heavily impact
      photocatalytic performance. The design of active photocatalysts has been
      performed with the consideration of such semiconductor properties. Photocatalysts
      have a catalytic aspect in addition to a semiconductor one. The ability to
      control surface redox reactions in order to efficiently produce targeted
      reactants is also important for photocatalysts. Over the past few decades,
      various photocatalysts for water splitting have been developed, and a recent main
      concern has been the development of visible-light sensitive photocatalysts for
      water splitting. This review introduces the study of water-splitting
      photocatalysts, with a focus on recent progress in visible-light induced overall
      water splitting on oxynitride photocatalysts. Various strategies for designing
      efficient photocatalysts for water splitting are also discussed herein.

PMID- 27877784
TI  - Exploration of new superconductors and functional materials, and fabrication of
      superconducting tapes and wires of iron pnictides.
AB  - This review shows the highlights of a 4-year-long research project supported by
      the Japanese Government to explore new superconducting materials and relevant
      functional materials. The project found several tens of new superconductors by
      examining ~1000 materials, each of which was chosen by Japanese experts with a
      background in solid state chemistry. This review summarizes the major
      achievements of the project in newly found superconducting materials, and the
      fabrication wires and tapes of iron-based superconductors; it incorporates a list
      of ~700 unsuccessful materials examined for superconductivity in the project. In
      addition, described are new functional materials and functionalities discovered
      during the project.

PMID- 27877788
TI  - Material research for environmental sustainability in Thailand: current trends.
AB  - This article covers recent developments of material research in Thailand with a
      focus on environmental sustainability. Data on Thailand's consumption and
      economic growth are briefly discussed to present a relevant snapshot of its
      economy. A selection of research work is classified into three topics, namely,
      (a) resource utilization, (b) material engineering and manufacturing, and (c)
      life cycle efficiency. Material technologies have been developed and implemented
      to reduce the consumption of materials, energy, and other valuable resources,
      thus reducing the burden we place on our ecological system. At the same time,
      product life cycle study allows us to understand the extent of the environmental
      impact we impart to our planet.

PMID- 27877789
TI  - Physico-chemical properties of biodiesel manufactured from waste frying oil using
      domestic adsorbents.
AB  - We have evaluated the efficiency of sugar cane bagasse ash (SCBA), date palm seed
      carbon (DPSC), and rice husk ash (RHA) as natural adsorbents and compared them
      with the synthetic adsorbent Magnesol XL for improving the quality of waste
      frying oil (WFO) and for the impact on the physicochemical properties of the
      obtained biodiesel. We measured moisture content, refractive index (RI), density,
      acid value (AV), iodine value (IV), peroxide value (PV), and saponification value
      (SV), as well as fatty acid profile. Purification treatments with various levels
      of adsorbents caused significant (P <= 0.05) decreases in free fatty acids
      (FFAs), PVs, and IVs. The highest yields (86.45 and 87.80%) were observed for
      biodiesel samples produced from WFO treated with 2% Magnesol and 3% of RHA,
      respectively, followed by samples treated with 2 and 3% of DPSC or RHA. Pre
      treatments caused a significant decrease in the content of C 18:2 linoleic acids,
      consistent with a significant increase in the content of monounsaturated and
      saturated fatty acids (MUFA) in the treated samples. The highest oxidation value
      (COX) (1.30) was observed for biodiesel samples produced from WFO without
      purification treatments. However, the lowest values (0.44-0.73) were observed for
      biodiesel samples produced from WFO treated with different levels of adsorbents.
      Our results indicate that pre-treatments with different levels of adsorbents
      regenerated the quality of WFO and improved the quality of the obtained
      biodiesel.

PMID- 27877790
TI  - How meaningful are risk determinations in the absence of a complete dataset?
      Making the case for publishing standardized test guideline and 'no effect'
      studies for evaluating the safety of nanoparticulates versus spurious 'high
      effect' results from single investigative studies.
AB  - A recent review article critically assessed the effectiveness of published
      research articles in nanotoxicology to meaningfully address health and safety
      issues for workers and consumers. The main conclusions were that, based on a
      number of flaws in study designs, the potential risk from exposures to
      nanomaterials is highly exaggerated, and that no 'nano-specific' adverse effects,
      different from exposures to bulk particles, have been convincingly demonstrated.
      In this brief editorial we focus on a related tangential issue which potentially
      compromises the integrity of basic risk science. We note that some single
      investigation studies report specious toxicity findings, which make the
      conclusions more alarming and attractive and publication worthy. In contrast, the
      standardized, carefully conducted, 'guideline study results' are often ignored
      because they can frequently report no adverse effects; and as a consequence are
      not considered as novel findings for publication purposes, and therefore they are
      never considered as newsworthy in the popular press. Yet it is the Organization
      for Economic Cooperation and Development (OECD) type test guideline studies that
      are the most reliable for conducting risk assessments. To contrast these styles
      and approaches, we present the results of a single study which reports high
      toxicological effects in rats following low-dose, short-term oral exposures to
      nanoscale titanium dioxide particles concomitant with selective investigative
      analyses. Alternatively, the findings of OECD test guideline 408, standardized
      guideline oral toxicity studies conducted for 90 days at much higher doses (1000
      mg kg-1) in male and female rats demonstrated no adverse effects following a very
      thorough and complete clinical chemical, as well as histopathological evaluation
      of all of the relevant organs in the body. This discrepancy in study findings is
      not reconciled by the fact that several biokinetic studies in rats and humans
      demonstrate little or no uptake of nanoscale or pigment-grade TiO2 particles
      following oral exposures. We conclude that to develop a competent risk assessment
      profile, results derived from standardized, guideline-type studies, and even 'no
      effect' study findings provide critically useful input for assessing safe levels
      of exposure; and should, in principle, be readily acceptable for publication in
      peer-reviewed toxicology journals. This is a necessary prerequisite for
      developing a complete dataset for risk assessment determinations.

PMID- 27877791
TI  - ATRP-based synthesis and characterization of light-responsive coatings for
      transdermal delivery systems.
AB  - The grafting of poly(hydroxyethylmethacrylate) on polymeric porous membranes via
      atom transfer radical polymerization (ATRP) and subsequent modification with a
      photo-responsive spiropyran derivative is described. This method leads to photo
      responsive membranes with desirable properties such as light-controlled
      permeability changes, exceptional photo-stability and repeatability of the photo
      responsive switching. Conventional track etched polyester membranes were first
      treated with plasma polymer coating introducing anchoring groups, which allowed
      the attachment of ATRP-initiator molecules on the membrane surface. Surface
      initiated ARGET-ATRP of hydroxyethylmethacrylate (where ARGET stands for
      activator regenerated by electron transfer) leads to a membrane covered with a
      polymer layer, whereas the controlled polymerization procedure allows good
      control over the thickness of the polymer layer in respect to the polymerization
      conditions. Therefore, the final permeability of the membranes could be tailored
      by choice of pore diameter of the initial membranes, applied monomer
      concentration or polymerization time. Moreover a remarkable switch in
      permeability (more than 1000%) upon irradiation with UV-light could be achieved.
      These properties enable possible applications in the field of transdermal drug
      delivery, filtration, or sensing.

PMID- 27877792
TI  - Geosynthetics in geoenvironmental engineering.
AB  - Geosynthetics are planar polymeric products, which are used in connection with
      soil, rock or other soil-like materials to fulfill various functions in
      geoenvironmental engineering. Geosynthetics are of ever-growing importance in the
      construction industry. Sealing of waste storage facilities to safely prevent the
      emission of wastewater, landfill gas and contaminated dust as well as the
      diffusion of pollutants into the environment and coastal protection against
      storms and floods and reconstruction after natural disaster are important fields
      of application. We will give an overview of the various geosynthetic products.
      Two examples of the material problems related to geosynthetics are discussed in
      detail: the effect of creep on the long-term performance of geocomposite drains
      and the numerical simulation of the interaction of soil with geogrids. Both
      issues are of importance for the use of these products in landfill capping
      systems. The various functions, which geosynthetics may fulfill in the protection
      of coastal lines, are illustrated by case studies. The geosynthetic market is
      evaluated and economical and environmental benefits, as well as environmental
      side effects related to the use of geosynthetics, are discussed.

PMID- 27877793
TI  - In vitro investigations of a novel wound dressing concept based on biodegradable
      polyurethane.
AB  - Non-healing and partially healing wounds are an important problem not only for
      the patient but also for the public health care system. Current treatment
      solutions are far from optimal regarding the chosen material properties as well
      as price and source. Biodegradable polyurethane (PUR) scaffolds have shown great
      promise for in vivo tissue engineering approaches, but accomplishment of the goal
      of scaffold degradation and new tissue formation developing in parallel has not
      been observed so far in skin wound repair. In this study, the mechanical
      properties and degradation behavior as well as the biocompatibility of a low-cost
      synthetic, pathogen-free, biocompatible and biodegradable extracellular matrix
      mimicking a PUR scaffold was evaluated in vitro. The novel PUR scaffolds were
      found to meet all the requirements for optimal scaffolds and wound dressings.
      These three-dimensional scaffolds are soft, highly porous, and form-stable and
      can be easily cut into any shape desired. All the material formulations
      investigated were found to be nontoxic. One formulation was able to be defined
      that supported both good fibroblast cell attachment and cell proliferation to
      colonize the scaffold. Tunable biodegradation velocity of the materials could be
      observed, and the results additionally indicated that calcium plays a crucial
      role in PUR degradation. Our results suggest that the PUR materials evaluated in
      this study are promising candidates for next-generation wound treatment systems
      and support the concept of using foam scaffolds for improved in vivo tissue
      engineering and regeneration.

PMID- 27877794
TI  - Towards sensor array materials: can failure be delayed?
AB  - Further to prior development in enhancing structural health using smart
      materials, an innovative class of materials characterized by the ability to feel
      senses like humans, i.e. 'nervous materials', is discussed. Designed at all
      scales, these materials will enhance personnel and public safety, and secure
      greater reliability of products. Materials may fail suddenly, but any system
      wishes that failure is known in good time and delayed until safe conditions are
      reached. Nervous materials are expected to be the solution to this statement.
      This new class of materials is based on the novel concept of materials capable of
      feeling multiple structural and external stimuli, e.g. stress, force, pressure
      and temperature, while feeding information back to a controller for appropriate
      real-time action. The strain-stress state is developed in real time with the
      identified and characterized source of stimulus, with optimized time response to
      retrieve initial specified conditions, e.g. shape and strength. Sensors are
      volumetrically embedded and distributed, emulating the human nervous system.
      Immediate applications are in aircraft, cars, nuclear energy and robotics. Such
      materials will reduce maintenance costs, detect initial failures and delay them
      with self-healing. This article reviews the common aspects and challenges
      surrounding this new class of materials with types of sensors to be embedded
      seamlessly or inherently, including appropriate embedding manufacturing
      techniques with modeling and simulation methods.

PMID- 27877796
TI  - Long-term exposure of bacterial and protozoan communities to TiO2 nanoparticles
      in an aerobic-sequencing batch reactor.
AB  - Titanium dioxide (TiO2) nanopowders at different concentrations (0-50 mg L-1)
      were injected into an aerobic-sequencing batch reactor (SBR) to investigate the
      effects of long-term exposure to nanoparticles on bacterial and protozoan
      communities. The detection of nanoparticles in the bioflocs was analyzed by
      scanning electron microscopy, transmission electron microscopy, and energy
      dispersive x-ray spectroscopy. The SBR wastewater experiments were conducted
      under the influence of ultraviolet light with photocatalytic TiO2. The intrusion
      of TiO2 nanoparticles was found both on the surface and inside of the bioflocs.
      The change of microbial population in terms of mixed liquor-suspended solids and
      the sludge volume index was monitored. The TiO2 nanoparticles tentatively exerted
      an adverse effect on the microbial population, causing the reduction of
      microorganisms (both bacteria and protozoa) in the SBR. The respiration
      inhibition rate of the bacteria was increased, and the viability of the microbial
      population was reduced at the high concentration (50 mg L-1) of TiO2. The
      decreasing number of protozoa in the presence of TiO2 nanoparticles during 20
      days of treatment with 0.5 and 1.0 mg L-1 TiO2 is clearly demonstrated. The
      measured chemical oxygen demand (COD) in the effluent tends to increase with a
      long-term operation. The increase of COD in the system suggests a decrease in the
      efficiency of the wastewater treatment plant. However, the SBR can effectively
      remove the TiO2 nanoparticles (up to 50 mg L-1) from the effluent.

PMID- 27877795
TI  - Cellular uptake and cell-to-cell transfer of polyelectrolyte microcapsules within
      a triple co-culture system representing parts of the respiratory tract.
AB  - Polyelectrolyte multilayer microcapsules around 3.4 micrometers in diameter were
      added to epithelial cells, monocyte-derived macrophages, and dendritic cells in
      vitro and their uptake kinetics were quantified. All three cell types were
      combined in a triple co-culture model, mimicking the human epithelial alveolar
      barrier. Hereby, macrophages were separated in a three-dimensional model from
      dendritic cells by a monolayer of epithelial cells. While passing of small
      nanoparticles has been demonstrated from macrophages to dendritic cells across
      the epithelial barrier in previous studies, for the micrometer-sized capsules,
      this process could not be observed in a significant amount. Thus, this barrier is
      a limiting factor for cell-to-cell transfer of micrometer-sized particles.

PMID- 27877798
TI  - Cupric oxide inclusions in cuprous oxide crystals grown by the floating zone
      method.
AB  - Phase-pure cuprous oxide (Cu2O) crystals are difficult to grow since cupric oxide
      can form within the crystal as the crystal is cooled to ambient conditions.
      Vacancies are the solute which causes precipitation of macroscopic defects.
      Therefore, even when a mostly phase-pure single crystal is used as a feed rod,
      cupric oxide inclusions persist in the recrystallized solid. Control of the
      thermal profile during crystal growth, however, can improve phase-purity; a slow
      counter-rotation rate of the feed and seed rods results in fewer inclusions.
      Cupric oxide can be removed by annealing, which produces a factor of 540 +/- 70
      increase in phase-purity.

PMID- 27877799
TI  - The effects of electric field and gate bias pulse on the migration and stability
      of ionized oxygen vacancies in amorphous In-Ga-Zn-O thin film transistors.
AB  - Oxygen vacancies have been considered as the origin of threshold voltage
      instability under negative bias illumination stress in amorphous oxide thin film
      transistors. Here we report the results of first-principles molecular dynamics
      simulations for the drift motion of oxygen vacancies. We show that oxygen
      vacancies, which are initially ionized by trapping photoexcited hole carriers,
      can easily migrate under an external electric field. Thus, accumulated hole traps
      near the channel/dielectric interface cause negative shift of the threshold
      voltage, supporting the oxygen vacancy model. In addition, we find that ionized
      oxygen vacancies easily recover their neutral defect configurations by capturing
      electrons when the Fermi level increases. Our results are in good agreement with
      the experimental observation that applying a positive gate bias pulse of short
      duration eliminates hole traps and thus leads to the recovery of device stability
      from persistent photoconductivity.

PMID- 27877797
TI  - Interaction of gold nanoparticles with proteins and cells.
AB  - Gold nanoparticles (Au NPs) possess many advantages such as facile synthesis,
      controllable size and shape, good biocompatibility, and unique optical
      properties. Au NPs have been widely used in biomedical fields, such as
      hyperthermia, biocatalysis, imaging, and drug delivery. The broad application
      range may result in hazards to the environment and human health. Therefore, it is
      important to predict safety and evaluate therapeutic efficiency of Au NPs. It is
      necessary to establish proper approaches for the study of toxicity and biomedical
      effects. In this review, we first focus on the recent progress in biological
      effects of Au NPs at the molecular and cellular levels, and then introduce key
      techniques to study the interaction between Au NPs and proteins. Knowledge of the
      biomedical effects of Au NPs is significant for the rational design of functional
      nanomaterials and will help predict their safety and potential applications.

PMID- 27877801
TI  - Negative thermal expansion induced by intermetallic charge transfer.
AB  - Suppression of thermal expansion is of great importance for industry. Negative
      thermal expansion (NTE) materials which shrink on heating and expand on cooling
      are therefore attracting keen attention. Here we provide a brief overview of NTE
      induced by intermetallic charge transfer in A-site ordered double perovskites
      SaCu3Fe4O12 and LaCu3Fe4-x Mn x O12, as well as in Bi or Ni substituted BiNiO3.
      The last compound shows a colossal dilatometric linear thermal expansion
      coefficient exceeding -70 * 10-6 K-1 near room temperature, in the temperature
      range which can be controlled by substitution.

PMID- 27877800
TI  - Recent progress in the development of solid catalysts for biomass conversion into
      high value-added chemicals.
AB  - In recent decades, the substitution of non-renewable fossil resources by
      renewable biomass as a sustainable feedstock has been extensively investigated
      for the manufacture of high value-added products such as biofuels, commodity
      chemicals, and new bio-based materials such as bioplastics. Numerous solid
      catalyst systems for the effective conversion of biomass feedstocks into value
      added chemicals and fuels have been developed. Solid catalysts are classified
      into four main groups with respect to their structures and substrate activation
      properties: (a) micro- and mesoporous materials, (b) metal oxides, (c) supported
      metal catalysts, and (d) sulfonated polymers. This review article focuses on the
      activation of substrates and/or reagents on the basis of groups (a)-(d), and the
      corresponding reaction mechanisms. In addition, recent progress in chemocatalytic
      processes for the production of five industrially important products (5
      hydroxymethylfurfural, lactic acid, glyceraldehyde, 1,3-dihydroxyacetone, and
      furan-2,5-dicarboxylic acid) as bio-based plastic monomers and their
      intermediates is comprehensively summarized.

PMID- 27877802
TI  - Silica/quercetin sol-gel hybrids as antioxidant dental implant materials.
AB  - The development of biomaterials with intrinsic antioxidant properties could
      represent a valuable strategy for preventing the onset of peri-implant diseases.
      In this context, quercetin, a naturally occurring flavonoid, has been entrapped
      at different weight percentages in a silica-based inorganic material by a sol-gel
      route. The establishment of hydrogen bond interactions between the flavonol and
      the solid matrix was ascertained by Fourier transform infrared spectroscopy. This
      technique also evidenced changes in the stretching frequencies of the quercetin
      dienonic moiety, suggesting that the formation of a secondary product occurs.
      Scanning electron microscopy was applied to detect the morphology of the
      synthesized materials. Their bioactivity was shown by the formation of a
      hydroxyapatite layer on sample surface soaked in a fluid that simulates the
      composition of human blood plasma. When the potential release of flavonol was
      determined by liquid chromatography coupled with ultraviolet and electrospray
      ionization tandem mass spectrometry techniques, the eluates displayed a retention
      time that was 0.5 min less than quercetin. Collision-activated dissociation mass
      spectrometry and untraviolet-visible spectroscopy were in accordance with the
      release of a quercetin derivative. The antiradical properties of the investigated
      systems were evaluated by DPPH and ABTS methods, whereas the 2,7
      dichlorofluorescein diacetate assay highlighted their ability to inhibit the H2O2
      induced intracellular production of reactive oxygen species in NIH-3T3 mouse
      fibroblast cells. Data obtained, along with data gathered from the MTT
      cytotoxicity test, revealed that the materials that entrapped the highest amount
      of quercetin showed notable antioxidant effectiveness.

PMID- 27877804
TI  - Influence of chemically p-type doped active organic semiconductor on the film
      thickness versus performance trend in cyanine/C60 bilayer solar cells.
AB  - Simple bilayer organic solar cells rely on very thin coated films that allow for
      effective light absorption and charge carrier transport away from the
      heterojunction at the same time. However, thin films are difficult to coat on
      rough substrates or over large areas, resulting in adverse shorting and low
      device fabrication yield. Chemical p-type doping of organic semiconductors can
      reduce Ohmic losses in thicker transport layers through increased conductivity.
      By using a Co(III) complex as chemical dopant, we studied doped cyanine dye/C60
      bilayer solar cell performance for increasing dye film thickness. For films
      thicker than 50 nm, doping increased the power conversion efficiency by more than
      30%. At the same time, the yield of working cells increased to 80%. We addressed
      the fate of the doped cyanine dye, and found no influence of doping on solar cell
      long term stability.

PMID- 27877803
TI  - Tribological investigation of diamond-like carbon coated micro-dimpled surface
      under bovine serum and osteoarthritis oriented synovial fluid.
AB  - Osteoarthritis-oriented synovial fluid (OASF), i.e., that typical of a patient
      with osteoarthritis, has different physical and biological characteristics than
      bovine serum (BS), a lubricant widely used in biotribological investigations.
      Micro-dimpled and diamond-like carbon- (DLC) coated surfaces are key emerging
      interfaces for orthopedic implants. In this study, tribological performances of
      dimpled surfaces, with and without DLC coating, have been investigated under both
      BS and OASF. The friction tests were performed utilizing a pin on a disk
      tribometer, whereas contact pressure, speed, and temperature were simulated to a
      'medium walking gait' of hip joint conditions. The mechanical properties of the
      specimen and the physical properties of the lubricant were characterized before
      the friction test. Raman analysis was conducted to identify the coating condition
      both before and after the test. The DLC-coated dimpled surface showed maximum
      hardness and residual stress. A DLC-coated dimpled surface under an OASF
      lubricated condition yielded a lower friction coefficient and wear compared to
      those of plain and dimpled specimens. The higher graphitization of coated
      materials with increasing load was confirmed by Raman spectroscopy.

PMID- 27877805
TI  - Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles
      for the neovascular imaging of orthotopic glioblastomas.
AB  - Introduction of ligands into 100 nm scaled hollow capsules has great potential
      for diagnostic and therapeutic applications in drug delivery systems.
      Polyethylene glycol-conjugated (PEGylated) polyion complex vesicles (PICsomes)
      are promising hollow nano-capsules that can survive for long periods in the blood
      circulation and can be used to deliver water-soluble macromolecules to target
      tissues. In this study, cyclic RGD (cRGD) peptide, which is specifically
      recognized by alphaVbeta3 and alphavbeta5 integrins that are expressed at high
      levels in the neovascular system, was conjugated onto the distal end of PEG
      strands on PICsomes for active neovascular targeting. Density-tunable cRGD
      conjugation was achieved using PICsomes with definite fraction of end
      functionalized PEG, to substitute 20, 40, and 100% of PEG distal end of the
      PICsomes to cRGD moieties. Compared with control-PICsomes without cRGD, cRGD
      PICsomes exhibited increased uptake into human umbilical vein endothelial cells.
      Intravital confocal laser scanning microscopy revealed that the 40%-cRGD-PICsomes
      accumulated mainly in the tumor neovasculature and remained in the perivascular
      region even after 24 h. Furthermore, we prepared superparamagnetic iron oxide
      (SPIO)-loaded cRGD-PICsomes for magnetic resonance imaging (MRI) and successfully
      visualized the neovasculature in an orthotopic glioblastoma model, which suggests
      that SPIO-loaded cRGD-PICsomes might be useful as a MRI contrast reagent for
      imaging of the tumor microenvironment, including neovascular regions that
      overexpress alphaVbeta3 integrins.

PMID- 27877806
TI  - Ultraviolet-nanoimprinted packaged metasurface thermal emitters for infrared CO2
      sensing.
AB  - Packaged dual-band metasurface thermal emitters integrated with a resistive
      membrane heater were manufactured by ultraviolet (UV) nanoimprint lithography
      followed by monolayer lift-off based on a soluble UV resist, which is mass
      producible and cost-effective. The emitters were applied to infrared CO2 sensing.
      In this planar Au/Al2O3/Au metasurface emitter, orthogonal rectangular Au patches
      are arrayed alternately and exhibit nearly perfect blackbody emission at 4.26 and
      3.95 MUm necessary for CO2 monitoring at the electric power reduced by 31%. The
      results demonstrate that metasurface infrared thermal emitters are almost ready
      for commercialization.

PMID- 27877807
TI  - Effects of fluoridation of porcine hydroxyapatite on osteoblastic activity of
      human MG63 cells.
AB  - Biological hydroxyapatite, derived from animal bones, is the most widely used
      bone substitute in orthopedic and dental treatments. Fluorine is the trace
      element involved in bone remodeling and has been confirmed to promote
      osteogenesis when administered at the appropriate dose. To take advantage of this
      knowledge, fluorinated porcine hydroxyapatite (FPHA) incorporating increasing
      levels of fluoride was derived from cancellous porcine bone through
      straightforward chemical and thermal treatments. Physiochemical characteristics,
      including crystalline phases, functional groups and dissolution behavior, were
      investigated on this novel FPHA. Human osteoblast-like MG63 cells were cultured
      on the FPHA to examine cell attachment, cytoskeleton, proliferation and
      osteoblastic differentiation for in vitro cellular evaluation. Results suggest
      that fluoride ions released from the FPHA play a significant role in stimulating
      osteoblastic activity in vitro, and appropriate level of fluoridation (1.5 to 3.1
      atomic percents of fluorine) for the FPHA could be selected with high potential
      for use as a bone substitute.

PMID- 27877808
TI  - Tribological and thermal stability study of nanoporous amorphous boron carbide
      films prepared by pulsed plasma chemical vapor deposition.
AB  - In this work, the thermal stability and the oxidation and tribological behavior
      of nanoporous a-BC:H films are studied and compared with those in conventional
      diamond-like carbon (DLC) films. a-BC:H films were deposited by pulsed plasma
      chemical vapor deposition using B(CH3)3 gas as the boron source. A DLC interlayer
      was used to prevent the a-BC:H film delamination produced by oxidation. Thermal
      stability of a-BC:H films, with no delamination signs after annealing at 500 
      degrees C for 1 h, is better than that of the DLC films, which completely
      disappeared under the same conditions. Tribological test results indicate that
      the a-BC:H films, even with lower nanoindentation hardness than the DLC films,
      show an excellent boundary oil lubricated behavior, with lower friction
      coefficient and reduce the wear rate of counter materials than those on the DLC
      film. The good materials properties such as low modulus of elasticity and the
      formation of micropores from the original nanopores during boundary regimes
      explain this better performance. Results show that porous a-BC:H films may be an
      alternative for segmented DLC films in applications where severe tribological
      conditions and complex shapes exist, so surface patterning is unfeasible.

PMID- 27877809
TI  - Texture design for microwave dielectric (Ca0.7Nd0.3)0.87TiO3 ceramics through
      reactive-templated grain growth.
AB  - Plate-like Ca3Ti2O7 (CT) and Nd2Ti2O7 (NT) particles were synthesized in molten
      salts and used as reactive templates for the preparation of highly textured
      (Ca0.7Nd0.3)0.87TiO3 bulk ceramics (CNT) with preferred pseudocubic <100> and
      <110> orientations, respectively. During flux growth CT and NT particles
      developed facets parallel to the pseudocubic {100} and {110} planes,
      respectively, in a perovskite unit cell, since those planes correspond to the
      interlayers of the layered perovskite-type crystal structures. Complementary
      reactants for the CNT stoichiometry were wet-mixed with the reactive templates
      and the slurries were tape-cast. Then stacked tapes were heat-treated for dense
      single-phase CNT ceramics with a distorted and A-site deficient regular
      perovskite-type structure. The CNT ceramics prepared with CT and NT reactive
      templates exhibited strong pseudocubic 100- and 110-family x-ray diffraction
      peaks, respectively, with other peaks drastically suppressed when non-perovskite
      sources were used as complementary reactants. The textured ceramics possess
      unique microstructures; as either parallel or obliquely stacked block structures
      with a pseudocubic {100} plane faceted. The pseudocubic {100}-and {110}-textured
      CNT ceramics exhibited ~10 and ~20% higher products of the dielectric quality
      factor and frequency, Q . f, respectively, than conventional ceramic sintered at
      the same temperature. When Q . f is compared based on the same grain size, the
      {100}-textured CNT exhibited 27% higher values than non-textured while relative
      permittivity and temperature coefficient of resonant frequency were of similar
      values. Simple geometrical relationships between electric field and penetrated
      pseudocubic {hk0}-type grain boundaries must lead to the reduced scattering and
      dielectric loss.

PMID- 27877810
TI  - Chemical doping of MoS2 multilayer by p-toluene sulfonic acid.
AB  - We report the tailoring of the electrical properties of mechanically exfoliated
      multilayer (ML) molybdenum disulfide (MoS2) by chemical doping. Electrical charge
      transport and Raman spectroscopy measurements revealed that the p-toluene
      sulfonic acid (PTSA) imposes n-doping in ML MoS2. The shift of threshold voltage
      for ML MoS2 transistor was analyzed as a function of reaction time. The threshold
      voltage shifted toward more negative gate voltages with increasing reaction time,
      which indicates an n-type doping effect. The shift of the Raman peak positions
      was also analyzed as a function of reaction time. PTSA treatment improved the
      field-effect mobility by a factor of ~4 without degrading the electrical
      characteristics of MoS2 devices.

PMID- 27877811
TI  - Lanthanide sorbent based on magnetite nanoparticles functionalized with
      organophosphorus extractants.
AB  - In this work, an adsorbent was prepared based on the attachment of
      organophosphorus acid extractants, namely, D2EHPA, CYANEX 272, and CYANEX 301, to
      the surface of superparamagnetic magnetite (Fe3O4) nanoparticles. The synthesized
      nanoparticles were coated with oleic acid, first by a chemisorption mechanism and
      later by the respective extractant via physical adsorption. The obtained core
      shell functionalized magnetite nanoparticle composites were characterized by
      dynamic light scattering, scanning electron microscopy, transmission electron
      microscopy, thermogravimetry, infrared absorption and vibrating sample
      magnetometry. All the prepared nanoparticles exhibited a high saturation
      magnetization capacity that varied between 72 and 46 emu g-1 and decreased as the
      magnetite nanoparticle was coated with oleic acid and functionalized. The scope
      of this study also included adsorption tests for lanthanum, cerium, praseodymium,
      and neodymium and the corresponding analysis of their results. Sorption tests
      indicated that the functionalized nanoparticles were able to extract the four
      studied lanthanide metal ions, although the best extraction performance was
      observed when the sorbent was functionalized with CYANEX 272, which resulted in a
      loading capacity of approximately 12-14 mgLa/gMNP. The magnetization of the
      synthesized nanoparticles was verified during the separation of the lanthanide
      loaded sorbent from the raffinate by using a conventional magnet.

PMID- 27877812
TI  - Some current problems in perovskite nano-ferroelectrics and multiferroics:
      kinetically-limited systems of finite lateral size.
AB  - We describe some unsolved problems of current interest; these involve quantum
      critical points in ferroelectrics and problems which are not amenable to the
      usual density functional theory, nor to classical Landau free energy approaches
      (they are kinetically limited), nor even to the Landau-Kittel relationship for
      domain size (they do not satisfy the assumption of infinite lateral diameter)
      because they are dominated by finite aperiodic boundary conditions.

PMID- 27877814
TI  - Varied roles of Pb in transition-metal PbMO3 perovskites (M = Ti, V, Cr, Mn, Fe,
      Ni, Ru).
AB  - Different structural chemistries resulting from the Pb2+ lone-pair electrons in
      the PbMO3 perovskites are reviewed. The Pb2+ lone-pair electrons enhance the
      ferroelectric transition temperature in PbTiO3, stabilize vanadyl formation in
      PbVO3, and induce a disproportionation reaction of CrIV in PbCrO3. A Pb2+ + NiIV
      = Pb4+ + NiII reaction in PbNiO3 stabilizes the LiNbO3 structure at ambient
      pressure, but an A-site Pb4+ in an orthorhombic perovskite PbNiO3 is stabilized
      at modest pressures at room temperature. In PbMnO3, a ferroelectric displacement
      due to the lone pair electron effect is minimized by the spin-spin exchange
      interaction and the strong octahedral site preference of the MnIV/III cation.
      PbRuO3 is converted under pressure from the defective pyrochlore to the
      orthorhombic (Pbnm) perovskite structure where Pb-Ru interactions via a common O 
      2p orbital stabilize at low temperature a metallic Imma phase at ambient
      pressure. Above Pc [Formula: see text] a covalent Pb-Ru bond is formed by Pb2+ +
      RuIV = Pb4+ + RuII electron sharing.

PMID- 27877813
TI  - Perovskite-type catalytic materials for environmental applications.
AB  - Perovskites are mixed-metal oxides that are attracting much scientific and
      application interest owing to their low price, adaptability, and thermal
      stability, which often depend on bulk and surface characteristics. These
      materials have been extensively explored for their catalytic, electrical,
      magnetic, and optical properties. They are promising candidates for the
      photocatalytic splitting of water and have also been extensively studied for
      environmental catalysis applications. Oxygen and cation non-stoichiometry can be
      tailored in a large number of perovskite compositions to achieve the desired
      catalytic activity, including multifunctional catalytic properties. Despite the
      extensive uses, the commercial success for this class of perovskite-based
      catalytic materials has not been achieved for vehicle exhaust emission control or
      for many other environmental applications. With recent advances in synthesis
      techniques, including the preparation of supported perovskites, and increasing
      understanding of promoted substitute perovskite-type materials, there is a
      growing interest in applied studies of perovskite-type catalytic materials. We
      have studied a number of perovskites based on Co, Mn, Ru, and Fe and their
      substituted compositions for their catalytic activity in terms of diesel soot
      oxidation, three-way catalysis, N2O decomposition, low-temperature CO oxidation,
      oxidation of volatile organic compounds, etc. The enhanced catalytic activity of
      these materials is attributed mainly to their altered redox properties, the
      promotional effect of co-ions, and the increased exposure of catalytically active
      transition metals in certain preparations. The recent lowering of sulfur content
      in fuel and concerns over the cost and availability of precious metals are
      responsible for renewed interest in perovskite-type catalysts for environmental
      applications.

PMID- 27877815
TI  - Recent progress in efficient hybrid lead halide perovskite solar cells.
AB  - The efficiency of perovskite solar cells (PSCs) has been improved from 9.7 to
      19.3%, with the highest value of 20.1% achieved in 2014. Such a high photovoltaic
      performance can be attributed to optically high absorption characteristics and
      balanced charge transport properties with long diffusion lengths of the hybrid
      lead halide perovskite materials. In this review, some fundamental details of
      hybrid lead iodide perovskite materials, various fabrication techniques and
      device structures are described, aiming for a better understanding of these
      materials and thus highly efficient PSC devices. In addition, some advantages and
      open issues are discussed here to outline the prospects and challenges of using
      perovskites in commercial photovoltaic devices.

PMID- 27877817
TI  - A meta-analysis of the mechanical properties of ice-templated ceramics and
      metals.
AB  - Ice templating, also known as freeze casting, is a popular shaping route for
      macroporous materials. Over the past 15 years, it has been widely applied to
      various classes of materials, and in particular ceramics. Many formulation and
      process parameters, often interdependent, affect the outcome. It is thus
      difficult to understand the various relationships between these parameters from
      isolated studies where only a few of these parameters have been investigated. We
      report here the results of a meta analysis of the structural and mechanical
      properties of ice templated materials from an exhaustive collection of records.
      We use these results to identify which parameters are the most critical to
      control the structure and properties, and to derive guidelines for optimizing the
      mechanical response of ice templated materials. We hope these results will be a
      helpful guide to anyone interested in such materials.

PMID- 27877818
TI  - Growth and applications of GeSn-related group-IV semiconductor materials.
AB  - We review the technology of Ge1-x Sn x -related group-IV semiconductor materials
      for developing Si-based nanoelectronics. Ge1-x Sn x -related materials provide
      novel engineering of the crystal growth, strain structure, and energy band
      alignment for realising various applications not only in electronics, but also in
      optoelectronics. We introduce our recent achievements in the crystal growth of
      Ge1-x Sn x -related material thin films and the studies of the electronic
      properties of thin films, metals/Ge1-x Sn x , and insulators/Ge1-x Sn x
      interfaces. We also review recent studies related to the crystal growth, energy
      band engineering, and device applications of Ge1-x Sn x -related materials, as
      well as the reported performances of electronic devices using Ge1-x Sn x related
      materials.

PMID- 27877816
TI  - A review of molecular beam epitaxy of ferroelectric BaTiO3 films on Si, Ge and
      GaAs substrates and their applications.
AB  - SrTiO3 epitaxial growth by molecular beam epitaxy (MBE) on silicon has opened up
      the route to the monolithic integration of various complex oxides on the
      complementary metal-oxide-semiconductor silicon platform. Among functional
      oxides, ferroelectric perovskite oxides offer promising perspectives to improve
      or add functionalities on-chip. We review the growth by MBE of the ferroelectric
      compound BaTiO3 on silicon (Si), germanium (Ge) and gallium arsenide (GaAs) and
      we discuss the film properties in terms of crystalline structure, microstructure
      and ferroelectricity. Finally, we review the last developments in two areas of
      interest for the applications of BaTiO3 films on silicon, namely integrated
      photonics, which benefits from the large Pockels effect of BaTiO3, and low power
      logic devices, which may benefit from the negative capacitance of the
      ferroelectric.

PMID- 27877819
TI  - Carbon fluoroxide nanoparticles as fluorescent labels and sonosensitizers for
      theranostic applications.
AB  - Carbon fluoroxide (CFO) nanoparticles (NPs) produced from silicon carbide wafers
      are used as both fluorescent probes and sonosensitizers for theranostic
      application. In vitro cell tests were carried out to investigate the feasibility
      of ultrasound-based therapy with the use of the CFO NPs. The NPs that penetrated
      inside the cells were shown to provoke cell destruction after application of an
      ultrasound treatment. No significant toxic effect was observed when the cells
      were treated with NP concentrations up to 0.5 mg ml-1 without applying ultrasound
      treatment. The obtained results open a new way toward cancer therapy strategies.

PMID- 27877820
TI  - Transfer studies of polystyrene nanoparticles in the ex vivo human placenta
      perfusion model: key sources of artifacts.
AB  - Nanotechnology is a rapidly expanding and highly promising new technology with
      many different fields of application. Consequently, the investigation of
      engineered nanoparticles in biological systems is steadily increasing. Questions
      about the safety of such engineered nanoparticles are very important and the most
      critical subject with regard to the penetration of biological barriers allowing
      particle distribution throughout the human body. Such translocation studies are
      technically challenging and many issues have to be considered to obtain
      meaningful and comparable results. Here we report on the transfer of polystyrene
      nanoparticles across the human placenta using an ex vivo human placenta perfusion
      model. We provide an overview of several challenges that can potentially occur in
      any translocation study in relation to particle size distribution,
      functionalization and stability of labels. In conclusion, a careful assessment of
      nanoparticle properties in a physiologically relevant milieu is as challenging
      and important as the actual study of nanoparticle-cell interactions itself.

PMID- 27877821
TI  - Evaluation of synovium-derived mesenchymal stem cells and 3D printed
      nanocomposite scaffolds for tissue engineering.
AB  - Stem cells and scaffolds play a very important role in tissue engineering. Here,
      we isolated synovium-derived mesenchymal stem cells (SMSCs) from synovial
      membrane tissue and characterized stem-cell properties. Gelatin nanoparticles
      (NP) were prepared using a two-step desolvation method and then pre-mixed into
      different host matrix (silk fibroin (SF), gelatin (Gel), or SF-Gel mixture) to
      generate various 3D printed nanocomposite scaffolds (NP/SF, NP/SF-Gel, NP/Gel-1,
      and NP/Gel-2). The microstructure was examined by scanning electron microscopy.
      Biocompatibility assessment was performed through CCK-8 assay by coculturing with
      SMSCs at 1, 3, 7 and 14 days. According to the results, SMSCs are similar to
      other MSCs in their surface epitope expression, which are negative for CD45 and
      positive for CD44, CD90, and CD105. After incubation in lineage-specific medium,
      SMSCs could differentiate into chondrocytes, osteocytes and adipocytes. 3D
      printed nanocomposite scaffolds exhibited a good biocompatibility in the process
      of coculturing with SMSCs and had no negative effect on cell behavior. The study
      provides a strategy to obtain SMSCs and fabricate 3D printed nanocomposite
      scaffolds, the combination of which could be used for practical applications in
      tissue engineering.

PMID- 27877822
TI  - Tribological performance of the biological components of synovial fluid in
      artificial joint implants.
AB  - The concentration of biological components of synovial fluid (such as albumin,
      globulin, hyaluronic acid, and lubricin) varies between healthy persons and
      osteoarthritis (OA) patients. The aim of the present study is to compare the
      effects of such variation on tribological performance in a simulated hip joint
      model. The study was carried out experimentally by utilizing a pin-on-disk
      simulator on ceramic-on-ceramic (CoC) and ceramic-on-polyethylene (CoP) hip joint
      implants. The experimental results show that both friction and wear of artificial
      joints fluctuate with the concentration level of biological components. Moreover,
      the performance also varies between material combinations. Wear debris sizes and
      shapes produced by ceramic and polyethylene were diverse. We conclude that the
      biological components of synovial fluid and their concentrations should be
      considered in order to select an artificial hip joint to best suit that patient.

PMID- 27877824
TI  - Multistate resistive switching in silver nanoparticle films.
AB  - Resistive switching devices have garnered significant consideration for their
      potential use in nanoelectronics and non-volatile memory applications. Here we
      investigate the nonlinear current-voltage behavior and resistive switching
      properties of composite nanoparticle films comprising a large collective of metal
      insulator-metal junctions. Silver nanoparticles prepared via the polyol process
      and coated with an insulating polymer layer of tetraethylene glycol were
      deposited onto silicon oxide substrates. Activation required a forming step
      achieved through application of a bias voltage. Once activated, the nanoparticle
      films exhibited controllable resistive switching between multiple discrete low
      resistance states that depended on operational parameters including the applied
      bias voltage, temperature and sweep frequency. The films' resistance switching
      behavior is shown here to be the result of nanofilament formation due to
      formative electromigration effects. Because of their tunable and distinct
      resistance states, scalability and ease of fabrication, nanoparticle films have a
      potential place in memory technology as resistive random access memory cells.

PMID- 27877823
TI  - Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)-the
      effect of biomolecular ligands to balance cell adhesion and stimulated
      detachment.
AB  - Two established material systems for thermally stimulated detachment of adherent
      cells were combined in a cross-linked polymer blend to merge favorable
      properties. Through this approach poly(N-isopropylacrylamide) (PNiPAAm) with its
      superior switching characteristic was paired with a poly(vinyl methyl ether)
      based composition that allows adjusting physico-chemical and biomolecular
      properties in a wide range. Beyond pure PNiPAAm, the proposed thermo-responsive
      coating provides thickness, stiffness and swelling behavior, as well as an
      apposite density of reactive sites for biomolecular functionalization, as
      effective tuning parameters to meet specific requirements of a particular cell
      type regarding initial adhesion and ease of detachment. To illustrate the
      strength of this approach, the novel cell culture carrier was applied to generate
      transplantable sheets of human corneal endothelial cells (HCEC). Sheets were
      grown, detached, and transferred onto planar targets. Cell morphology, viability
      and functionality were analyzed by immunocytochemistry and determination of
      transepithelial electrical resistance (TEER) before and after sheet detachment
      and transfer. HCEC layers showed regular morphology with appropriate TEER. Cells
      were positive for function-associated marker proteins ZO-1, Na+/K+-ATPase, and
      paxillin, and extracellular matrix proteins fibronectin, laminin and collagen
      type IV before and after transfer. Sheet detachment and transfer did not impair
      cell viability. Subsequently, a potential application in ophthalmology was
      demonstrated by transplantation onto de-endothelialized porcine corneas in vitro.
      The novel thermo-responsive cell culture carrier facilitates the generation and
      transfer of functional HCEC sheets. This paves the way to generate tissue
      engineered human corneal endothelium as an alternative transplant source for
      endothelial keratoplasty.

PMID- 27877825
TI  - Impact of monoolein on aquaporin1-based supported lipid bilayer membranes.
AB  - Aquaporin (AQP) based biomimetic membranes have attracted considerable attention
      for their potential water purification applications. In this paper, AQP1
      incorporated biomimetic membranes were prepared and characterized. The morphology
      and structure of the biomimetic membranes were characterized by in situ atomic
      force microscopy (AFM), infrared absorption spectroscopy, fluorescence
      microscopy, and contact angle measurements. The nanofiltration performance of the
      AQP1 incorporated membranes was investigated at 4 bar by using 2 g l-1 NaCl as
      feed solution. Lipid mobility plays an important role in the performance of the
      AQP1 incorporated supported lipid bilayer (SLB) membranes. We demonstrated that
      the lipid mobility is successfully tuned by the addition of monoolein (MO).
      Through in situ AFM and fluorescence recovery after photo-bleaching (FRAP)
      measurements, the membrane morphology and the molecular mobility were studied.
      The lipid mobility increased in the sequence DPPC < DPPC/MO (RMO = 5/5) < DOPC/MO
      (RMO = 5/5) < DOPC, which is consistent with the flux increment and salt
      rejection. This study may provide some useful insights for improving the water
      purification performance of biomimetic membranes.

PMID- 27877827
TI  - Glory of piezoelectric perovskites.
AB  - This article reviews the history of piezoelectric perovskites and forecasts
      future development trends, including Uchino's discoveries such as the
      Pb(Mg1/3Nb2/3)O3-PbTiO3 electrostrictor, Pb(Zn1/3Nb2/3)O3-PbTiO3 single crystal,
      (Pb, La)(Zr, Ti)O3 photostriction, and Pb(Zr, Ti)O3-Terfenol magnetoelectric
      composites. We discuss five key trends in the development of piezomaterials:
      performance to reliability, hard to soft, macro to nano, homo to hetero, and
      single to multi-functional.

PMID- 27877828
TI  - Focus on nanospace materials.

PMID- 27877826
TI  - Effect of amino groups of mesoporous silica nanoparticles on CpG
      oligodexynucleotide delivery.
AB  - In this study, we proposed to modify mesoporous silica nanoparticles (MSNs) with
      3-aminopropyltriethoxysilane (NH2-TES), aminoethylaminopropyltriethoxysilane
      (2NH2-TES) and 3-[2-(2-aminoethylamino)ethylamino] propyl-trimethoxysilane (3NH2
      TES) for binding of cytosine-phosphate-guanosine oligodexynucleotides (CpG ODN),
      and investigated the effect of different amino groups of MSNs on the CpG ODN
      delivery. Serum stability, in vitro cytotoxicity, and cytokine interleukin-6 (IL
      6) induction by MSN-NH2/CpG, MSN-2NH2/CpG and MSN-3NH2/CpG complexes were
      investigated in detail. The results showed that three kinds of aminated-MSN-based
      CpG ODN delivery systems had no cytotoxicity to RAW264.7 cells, and binding of
      CpG ODN to MSN-NH2, MSN-2NH2 and MSN-3NH2 nanoparticles enhanced the serum
      stability of CpG ODN due to protection by the nanoparticles. However, three
      aminated MSN-based CpG ODN delivery systems exhibited different CpG ODN delivery
      efficiency, and MSN-NH2/CpG complexes had the highest ability to induce IL-6
      secretion.

PMID- 27877829
TI  - Surface treatments for controlling corrosion rate of biodegradable Mg and Mg
      based alloy implants.
AB  - Due to their excellent biodegradability characteristics, Mg and Mg-based alloys
      have become an emerging material in biomedical implants, notably for repair of
      bone as well as coronary arterial stents. However, the main problem with Mg-based
      alloys is their rapid corrosion in aggressive environments such as human bodily
      fluids. Previously, many approaches such as control of alloying materials,
      composition and surface treatments, have been attempted to regulate the corrosion
      rate. This article presents a comprehensive review of recent research focusing on
      surface treatment techniques utilised to control the corrosion rate and surface
      integrity of Mg-based alloys in both in vitro and in vivo environments. Surface
      treatments generally involve the controlled deposition of thin film coatings
      using various coating processes, and mechanical surfacing such as machining, deep
      rolling or low plasticity burnishing. The aim is to either make a protective thin
      layer of a material or to change the micro-structure and mechanical properties at
      the surface and sub-surface levels, which will prevent rapid corrosion and thus
      delay the degradation of the alloys. We have organised the review of past works
      on coatings by categorising the coatings into two classes-conversion and
      deposition coatings-while works on mechanical treatments are reviewed based on
      the tool-based processes which affect the sub-surface microstructure and
      mechanical properties of the material. Various types of coatings and their
      processing techniques under two classes of coating and mechanical treatment
      approaches have been analysed and discussed to investigate their impact on the
      corrosion performance, biomechanical integrity, biocompatibility and cell
      viability. Potential challenges and future directions in designing and developing
      the improved biodegradable Mg/Mg-based alloy implants were addressed and
      discussed. The literature reveals that no solutions are yet complete and hence
      new and innovative approaches are required to leverage the benefit of Mg-based
      alloys. Hybrid treatments combining innovative biomimetic coating and mechanical
      processing would be regarded as a potentially promising way to tackle the
      corrosion problem. Synergetic cutting-burnishing integrated with cryogenic
      cooling may be another encouraging approach in this regard. More studies focusing
      on rigorous testing, evaluation and characterisation are needed to assess the
      efficacy of the methods.

PMID- 27877830
TI  - Host-guest chemistry of mesoporous silicas: precise design of location, density
      and orientation of molecular guests in mesopores.
AB  - Mesoporous solids, which were prepared from inorganic-surfactant mesostructured
      materials, have been investigated due to their very large surface area and high
      porosity, pore size uniformity and variation, periodic pore arrangement and
      possible pore surface modification. Morphosyntheses from macroscopic morphologies
      such as bulk monolith and films, to nanoscopic ones, nanoparticles and their
      stable suspension, make mesoporous materials more attractive for applications and
      detailed characterization. This class of materials has been studied for such
      applications as adsorbents and catalysts, and later on, for optical, electronic,
      environmental and bio-related ones. This review summarizes the studies on the
      chemistry of mesoporous silica and functional guest species (host-guest
      chemistry) to highlight the present status and future applications of the host
      guest hybrids.

PMID- 27877832
TI  - Carbonization and oxidation of metal-organic frameworks based on 1,4-naphthalene
      dicarboxylates.
AB  - Three new isostructural metal-organic frameworks (MOFs), [V(OH)(NDC)] (1),
      [Cr(OH)(NDC)] (2), and [Ga(OH)(NDC)] (3) have been synthesized hydrothermally
      using 1,4-naphthalene dicarboxylate (NDC) as the linker. These MOFs (1, 2 and 3)
      have been used as a template for the synthesis of metal-oxide-inserted nanoporous
      carbon materials. The newly synthesized MOFs and the resulting porous carbon
      hybrid functional materials have been characterized using powder x-ray
      diffraction, scanning electron microscopy, transmission electron microscopy, and
      energy dispersive x-ray spectroscopic analysis. Results show that compounds 2 and
      3 form their respective metal oxide nanoparticles on the surface of the carbon
      materials during carbonization at 800  degrees C. The gas sorption properties of
      the new MOFs and their corresponding carbon frameworks have been reported.

PMID- 27877833
TI  - Metal-organic frameworks for electronics: emerging second order nonlinear optical
      and dielectric materials.
AB  - Metal-organic frameworks (MOFs) have been intensively studied over the past
      decade because they represent a new category of hybrid inorganic-organic
      materials with extensive surface areas, ultrahigh porosity, along with the
      extraordinary tailorability of structure, shape and dimensions. In this
      highlight, we summarize the current state of MOF research and report on structure
      property relationships for nonlinear optical (NLO) and dielectric applications.
      We focus on the design principles and structural elements needed to develop
      potential NLO and low dielectric (low-kappa) MOFs with an emphasis on enhancing
      material performance. In addition, we highlight experimental evidence for the
      design of devices for low-dielectric applications. These results motivate us to
      develop better low-dielectric and NLO materials and to perform in-depth studies
      related to deposition techniques, patterning and the mechanical performance of
      these materials in the future.

PMID- 27877834
TI  - Encapsulation of palladium porphyrin photosensitizer in layered metal oxide
      nanoparticles for photodynamic therapy against skin melanoma.
AB  - We designed a biodegradable nanocarrier of layered double hydroxide (LDH) for
      photodynamic therapy (PDT) based on the intercalation of a palladium porphyrin
      photosensitizer (PdTCPP) in the gallery of LDH for melanoma theragnosis. Physical
      and chemical characterizations have demonstrated the photosensitizer was stable
      in the layered structures. In addition, the synthesized nanocomposites rendered
      extremely efficacious therapy in the B16F10 melanoma cell line by improving the
      solubility of the hydrophobic PdTCPP photosensitizer. The detection of singlet
      oxygen generation under irradiation at the excitation wavelength of a 532 nm
      laser was indeed impressive. Furthermore, the in vivo results using a tumour
      xenograft model in mice indicated the apparent absence of body weight loss and
      relative organ weight variation to the liver and kidney demonstrated that the
      nanocomposites were biosafe with a significant reduction in tumour volume for the
      anti-cancer efficacy of PDT. This drug delivery system using the nanoparticle
      photosensitizer hybrid has great potential in melanoma theragnosis.

PMID- 27877835
TI  - Hard-templating of chiral TiO2 nanofibres with electron transition-based optical
      activity.
AB  - The fabrication of optically active inorganic nanomaterials with chiral
      superstructures attracts attention because of their potential applications in
      chemical sensing and non-linear optics. Here, we present a facile way to prepare
      TiO2 nanofibres, in which the nanocrystals are helically arranged into a chiral
      superstructure. Notably, the chiral superstructure shows strong optical activity
      due to the difference of absorbing left- and right-handed circularly polarized
      light. This special optical activity resulted from electron transition from the
      valence band to the conduction band of TiO2 through a vicinal effect of helically
      arranged TiO2 nanocrystals.

PMID- 27877831
TI  - Recent progress in the synthesis of metal-organic frameworks.
AB  - Metal-organic frameworks (MOFs) have attracted considerable attention for various
      applications due to their tunable structure, porosity and functionality. In
      general, MOFs have been synthesized from isolated metal ions and organic linkers
      under hydrothermal or solvothermal conditions via one-spot reactions. The
      emerging precursor approach and kinetically tuned dimensional augmentation
      strategy add more diversity to this field. In addition, to speed up the
      crystallization process and create uniform crystals with reduced size, many
      alternative synthesis routes have been explored. Recent advances in microwave
      assisted synthesis and electrochemical synthesis are presented in this review. In
      recent years, post-synthetic approaches have been shown to be powerful tools to
      synthesize MOFs with modified functionality, which cannot be attained via de novo
      synthesis. In this review, some current accomplishments of post-synthetic
      modification (PSM) based on covalent transformations and coordinative
      interactions as well as post-synthetic exchange (PSE) in robust MOFs are
      provided.

PMID- 27877836
TI  - Experimental study and thermodynamic modeling of the Al-Co-Cr-Ni system.
AB  - A thermodynamic database for the Al-Co-Cr-Ni system is built via the Calphad
      method by extrapolating re-assessed ternary subsystems. A minimum number of
      quaternary parameters are included, which are optimized using experimental phase
      equilibrium data obtained by electron probe micro-analysis and x-ray diffraction
      analysis of NiCoCrAlY alloys spanning a wide compositional range, after annealing
      at 900  degrees C, 1100  degrees C and 1200  degrees C, and water quenching.
      These temperatures are relevant to oxidation and corrosion resistant MCrAlY
      coatings, where M corresponds to some combination of nickel and cobalt.
      Comparisons of calculated and measured phase compositions show excellent
      agreement for the beta-gamma equilibrium, and good agreement for three-phase beta
      gamma-sigma and beta-gamma-alpha equilibria. An extensive comparison with
      existing Ni-base databases (TCNI6, TTNI8, NIST) is presented in terms of phase
      compositions.

PMID- 27877837
TI  - Absorbing TiO x thin film enabling laser welding of polyurethane membranes and
      polyamide fibers.
AB  - We report on the optical properties of thin titanium suboxide (TiO x ) films for
      applications in laser transmission welding of polymers. Non-absorbing fibers were
      coated with TiO x coatings by reactive magnetron sputtering. Plasma process
      parameters influencing the chemical composition and morphology of the deposited
      thin films were investigated in order to optimize their absorption properties.
      Optical absorption spectroscopy showed that the oxygen content of the TiO x
      coatings is the main parameter influencing the optical absorbance. Overtreatment
      (high power plasma input) of the fiber surface leads to high surface roughness
      and loss of mechanical stability of the fiber. The study shows that thin
      substoichiometric TiO x films enable the welding of very thin polyurethane
      membranes and polyamide fibers with improved adhesion properties.

PMID- 27877839
TI  - A biosensor based on Coriolopsis gallica laccase immobilized on nitrogen-doped
      multiwalled carbon nanotubes and graphene oxide for polyphenol detection.
AB  - The use of nanomaterials allows the design of ultrasensitive biosensors with
      advantages in the detection of organic molecules. Catechol and catechin are
      molecules that occur naturally in fruits, and their presence in products like
      dyes and wines affects quality standards. In this study, catechol and catechin
      were measured at the nanoscale by means of cyclic voltammetry. The oxidation of
      Coriolopsis gallica laccase immobilized on nitrogen-doped multiwalled carbon
      nanotubes (Lac/CN x -MWCNT) and on graphene oxide (Lac/GO) was used to measure
      the concentrations of catechol and catechin. Nitrogen-doped multiwalled carbon
      nanotubes (CN x -MWCNT) were synthesized by spray pyrolysis and characterized by
      scanning electron microscopy (SEM), transmission electron microscopy (TEM), and x
      ray photoelectron spectroscopy (XPS). Covalently bonded hybrids with laccase
      (Lac/CN x -MWCNT and Lac/GO) were generated. Catalytic activity of free enzymes
      determined with syringaldazine yielded 14 584 UmL-1. With Lac/CN x -MWCNT at
      concentrations of 6.4 mmol L-1 activity was 9326 U mL-1, while enzyme activity
      measured with Lac/GO at concentration of 6.4 mmol L-1 was 9 234 U mL-1. The
      Lac/CN x -MWCNT hybrid showed higher stability than Lac/GO at different ethyl
      alcohol concentrations. The Lac/CN x -MWCNT hybrid can measure concentrations,
      not previously reported, as low as 1 * 10-8 mol L-1 by measuring the electric
      current responses.

PMID- 27877838
TI  - Synthesis of nanoparticle CT contrast agents: in vitro and in vivo studies.
AB  - Water-soluble and biocompatible D-glucuronic acid coated Na2WO4 and BaCO3
      nanoparticles were synthesized for the first time to be used as x-ray computed
      tomography (CT) contrast agents. Their average particle diameters were 3.2 +/-
      0.1 and 2.8 +/- 0.1 nm for D-glucuronic acid coated Na2WO4 and BaCO3
      nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray
      attenuation. In vivo CT images were obtained after intravenous injection of an
      aqueous sample suspension of D-glucuronic acid coated Na2WO4 nanoparticles, and
      positive contrast enhancements in the kidney were clearly shown. These findings
      indicate that the nanoparticles reported in this study may be promising CT
      contrast agents.

PMID- 27877840
TI  - Engineered silica nanoparticles as additives in lubricant oils.
AB  - Silica nanoparticles (SiO2 NPs) synthesized by the sol-gel approach were
      engineered for size and surface properties by grafting hydrophobic chains to
      prevent their aggregation and facilitate their contact with the phase boundary,
      thus improving their dispersibility in lubricant base oils. The surface
      modification was performed by covalent binding of long chain alkyl
      functionalities using lauric acid and decanoyl chloride to the SiO2 NP surface.
      The hybrid SiO2 NPs were characterized by scanning electron microscopy,
      transmission electron microscopy, Fourier transform infrared spectroscopy,
      simultaneous differential thermal analysis, nuclear magnetic resonance and
      dynamic light scattering, while their dispersion in two base oils was studied by
      static multiple light scattering at low (0.01% w/v) and high (0.50%w/v)
      concentrations. The nature of the functional layer and the functionalization
      degree seemed to be directly involved in the stability of the suspensions. The
      potential use of the functional SiO2 NPs as lubricant additives in base oils,
      specially designed for being used in hydraulic circuits, has been outlined by
      analyzing the tribological properties of the dispersions. The dendritic structure
      of the external layer played a key role in the tribological characteristics of
      the material by reducing the friction coefficient and wear. These nanoparticles
      reduce drastically the waste of energy in friction processes and are more
      environmentally friendly than other additives.

PMID- 27877841
TI  - Fabrication of optimized oil-water separation devices through the targeted
      treatment of silica meshes.
AB  - Efficient oil-water separation is achieved using an optimized superhydrophobic
      material, generated by the zeolitic roughening and subsequent hydrophobic surface
      treatment of silica filter membranes. The material is both highly rough and
      intrinsically hydrophobic, resulting in superhydrophobic membranes which show a
      substantial affinity for hydrophobic solvents and oils. The membranes are syringe
      mounted, suction pressure is applied and the selective collection of oil is
      achieved. The membranes are extremely robust, which is a result of the zeolitic
      roughening process, they possess small pores (0.7 MUm), as a result these devices
      can perform complete separation and operate at a range of suction pressures. The
      devices could be readily used in a range of real-world applications, including
      oil spill clean-up and industrial filters.

PMID- 27877842
TI  - Tuning light emission of PbS nanocrystals from infrared to visible range by
      cation exchange.
AB  - Colloidal semiconductor nanocrystals, with intense and sharp-line emission
      between red and near-infrared spectral regions, are of great interest for
      optoelectronic and bio-imaging applications. The growth of an inorganic
      passivation layer on nanocrystal surfaces is a common strategy to improve their
      chemical and optical stability and their photoluminescence quantum yield. In
      particular, cation exchange is a suitable approach for shell growth at the
      expense of the nanocrystal core size. Here, the cation exchange process is used
      to promote the formation of a CdS passivation layer on the surface of very small
      PbS nanocrystals (2.3 nm in diameter), blue shifting their optical spectra and
      yielding luminescent and stable nanostructures emitting in the range of 700-850
      nm. Structural, morphological and compositional investigation confirms the
      nanocrystal size contraction after the cation-exchange process, while the PbS
      rock-salt crystalline phase is retained. Absorption and photoluminescence
      spectroscopy demonstrate the growth of a passivation layer with a decrease of the
      PbS core size, as inferred by the blue-shift of the excitonic peaks. The surface
      passivation strongly increases the photoluminescence intensity and the excited
      state lifetime. In addition, the nanocrystals reveal increased stability against
      oxidation over time. Thanks to their absorption and emission spectral range and
      the slow recombination dynamics, such highly luminescent nano-objects can find
      interesting applications in sensitized photovoltaic cells and light-emitting
      devices.

PMID- 27877843
TI  - Thermally conductive polyamide 6/carbon filler composites based on a hybrid
      filler system.
AB  - We explored the use of a hybrid filler consisting of graphite nanoplatelets
      (GNPs) and single walled carbon nanotubes (SWCNTs) in a polyamide 6 (PA 6)
      matrix. The composites containing PA 6, powdered GNP, and SWCNT were melt
      processed and the effect of filler content in the single filler and hybrid filler
      systems on the thermal conductivity of the composites was examined. The thermal
      diffusivities of the composites were measured by the standard laser flash method.
      Composites containing the hybrid filler system showed enhanced thermal
      conductivity with values as high as 8.8 W (m . K)-1, which is a 35-fold increase
      compared to the thermal conductivity of pure PA 6. Thermographic images of heat
      conduction and heat release behaviors were consistent with the thermal
      conductivity results, and showed rapid temperature jumps and drops, respectively,
      for the composites. A composite model based on the Lewis-Nielsen theory was
      developed to treat GNP and SWCNT as two separate types of fillers. Two
      approaches, the additive and multiplicative approaches, give rather good
      quantitative agreement between the predicted values of thermal conductivity and
      those measured experimentally.

PMID- 27877844
TI  - Identifying and rationalizing the morphological, structural, and optical
      properties of [Formula: see text]-Ag2MoO4 microcrystals, and the formation
      process of Ag nanoparticles on their surfaces: combining experimental data and
      first-principles calculations.
AB  - We present a combined theoretical and experimental study on the morphological,
      structural, and optical properties of beta-Ag2MoO4 microcrystals. beta-Ag2MoO4
      samples were prepared by a co-precipitation method. The nucleation and formation
      of Ag nanoparticles on beta-Ag2MoO4 during electron beam irradiation were also
      analyzed as a function of electron beam dose. These events were directly
      monitored in real-time using in situ field emission scanning electron microscopy
      (FE-SEM). The thermodynamic equilibrium shape of the beta-Ag2MoO4 crystals was
      built with low-index surfaces (001), (011), and (111) through a Wulff
      construction. This shape suggests that the (011) face is the dominating surface
      in the ideal morphology. A significant increase in the values of the surface
      energy for the (011) face versus those of the other surfaces was observed, which
      allowed us to find agreement between the experimental and theoretical
      morphologies. Our investigation of the different morphologies and structures of
      the beta-Ag2MoO4 crystals provided insight into how the crystal morphology can be
      controlled so that the surface chemistry of beta-Ag2MoO4 can be tuned for
      specific applications. The presence of structural disorder in the tetrahedral
      [MoO4] and octahedral [AgO6] clusters, the building blocks of beta-Ag2MoO4, was
      used to explain the experimentally measured optical properties.

PMID- 27877845
TI  - Modulated interaction in double-layer shape memory-based micro-designed
      actuators.
AB  - The effect of superposed transitions in actuators with layered shape memory alloy
      (SMA) films undergoing martensitic phase transformation is analyzed in terms of a
      model developed for two layers of different composition, deposited at the same
      temperature on a substrate. A significant difference is observed in the actuation
      versus temperature relationship, depending on the thermal and elastic properties
      of the SMA layers and their martensitic transformation temperature. The
      prediction of the actuation is exemplified using a multilayer model and is
      verified for a cantilever actuator with NiTi and NiMnGa layers deposited on a Si
      substrate. The model sets the ground for a smart selection of SMAs in order to
      achieve a modulated actuation.

PMID- 27877847
TI  - Adsorption of amino acids by fullerenes and fullerene nanowhiskers.
AB  - We have investigated the adsorption of some amino acids and an oligopeptide by
      fullerene (C60) and fullerene nanowhiskers (FNWs). C60 and FNWs hardly adsorbed
      amino acids. Most of the amino acids used have a hydrophobic side chain. Ala and
      Val, with an alkyl chain, were not adsorbed by the C60 or FNWs. Trp, Phe and Pro,
      with a cyclic structure, were not adsorbed by them either. The aromatic group of
      C60 did not interact with the side chain. The carboxyl or amino group, with the
      frame structure of an amino acid, has a positive or negative charge in solution.
      It is likely that the C60 and FNWs would not prefer the charged carboxyl or amino
      group. Tri-Ala was adsorbed slightly by the C60 and FNWs. The carboxyl or amino
      group is not close to the center of the methyl group of Tri-Ala. One of the
      methyl groups in Tri-Ala would interact with the aromatic structure of the C60
      and FNWs. We compared our results with the theoretical interaction of 20 bio
      amino acids with C60. The theoretical simulations showed the bonding distance
      between C60 and an amino acid and the dissociation energy. The dissociation
      energy was shown to increase in the order, Val < Phe < Pro < Asp < Ala < Trp <
      Tyr < Arg < Leu. However, the simulation was not consistent with our experimental
      results. The adsorption of albumin (a protein) by C60 showed the effect on the
      side chains of Try and Trp. The structure of albumin was changed a little by C60.
      In our study Try and Tyr were hardly adsorbed by C60 and FNWs. These amino acids
      did not show a different adsorption behavior compared with other amino acids. The
      adsorptive behavior of mono-amino acids might be different from that of
      polypeptides.

PMID- 27877848
TI  - Towards sensible toxicity testing for nanomaterials: proposal for the
      specification of test design.
AB  - During the last decade, nanomaterials (NM) were extensively tested for potential
      harmful effects towards humans and environmental organisms. However, a sound
      hazard assessment was so far hampered by uncertainties and a low comparability of
      test results. The reason for the low comparability is a high variation in the (1)
      type of NM tested with regard to raw material, size and shape and (2) procedures
      before and during the toxicity testing. This calls for tailored, nanomaterial
      specific protocols. Here, a structured approach is proposed, intended to lead to
      test protocols not only tailored to specific types of nanomaterials, but also to
      respective test system for toxicity testing. There are existing standards on
      single procedures involving nanomaterials, however, not all relevant procedures
      are covered by standards. Hence, our approach offers a detailed way of weighting
      several plausible alternatives for e.g. sample preparation, in order to decide on
      the procedure most meaningful for a specific nanomaterial and toxicity test. A
      framework of several decision trees (DT) and flow charts to support testing of NM
      is proposed as a basis for further refinement and in-depth elaboration. DT and
      flow charts were drafted for (1) general procedure-physicochemical
      characterisation, (2) choice of test media, (3) decision on test scenario and
      application of NM to liquid media, (4) application of NM to the gas phase, (5)
      application of NM to soil and sediments, (6) dose metrics, (S1) definition of a
      nanomaterial, and (S2) dissolution. The applicability of the proposed approach
      was surveyed by using experimental data retrieved from studies on nanoscale CuO.
      This survey demonstrated the DT and flow charts to be a convenient tool to
      systematically decide upon test procedures and processes, and hence pose an
      important step towards harmonisation of NM testing.

PMID- 27877846
TI  - A label-free G-quadruplex-based mercury detection assay employing the exonuclease
      III-mediated cleavage of T-Hg2+-T mismatched DNA.
AB  - We report herein the use of an exonuclease III and G-quadruplex probe to
      construct a G-quadruplex-based luminescence detection platform for Hg2+. Unlike
      common DNA-based Hg2+ detection methods, when using the dsDNA probe to monitor
      the hairpin formation, the intercalation of the dsDNA probe may be influenced by
      the distortion of dsDNA. This 'mix-and-detect' methodology utilized the G
      quadruplex probe as the signal transducer and is simple, rapid, convenient to use
      and can detect down to 20 nM of Hg2+.

PMID- 27877849
TI  - Three-dimensional reconstruction of anomalous eutectic in laser remelted Ni-30
      wt.% Sn alloy.
AB  - Laser remelting has been performed on Ni-30 wt.% Sn hypoeutectic alloy. An
      anomalous eutectic formed at the bottom of the molten pool when the sample was
      remelted thoroughly. 3D morphologies of the alpha-Ni and Ni3Sn phases in the
      anomalous eutectic region were obtained and investigated using serial sectioning
      reconstruction technology. It is found that the Ni3Sn phase has a continuous
      interconnected network structure and the alpha-Ni phase is distributed as
      separate particles in the anomalous eutectic, which is consistent with the
      electron backscatter diffraction pattern examinations. The alpha-Ni particles in
      the anomalous eutectic are supersaturated with Sn element as compared with the
      equilibrium phase diagram. Meanwhile, small wavy lamella eutectics coexist with
      anomalous eutectics. The Trivedi-Magnin-Kurz model was used to estimate
      undercooling with lamellar spacing. The results suggest that the critical
      undercooling found in undercooling solidification is not a sufficient condition
      for anomalous eutectic formation. Besides, alpha-Ni particles in the anomalous
      eutectic do not exhibit a completely random misorientation and some neighboring
      alpha-Ni particles have the same orientation. It is shown that both the coupled
      and decoupled growth of the eutectic two phases can generate the alpha-Ni + Ni3Sn
      anomalous eutectic structure.

PMID- 27877851
TI  - New STAM, new horizon.

PMID- 27877850
TI  - Turning an organic semiconductor into a low-resistance material by ion
      implantation.
AB  - We report on the effects of low energy ion implantation on thin films of
      pentacene, carried out to investigate the efficacy of this process in the
      fabrication of organic electronic devices. Two different ions, Ne and N, have
      been implanted and compared, to assess the effects of different reactivity within
      the hydrocarbon matrix. Strong modification of the electrical conductivity,
      stable in time, is observed following ion implantation. This effect is
      significantly larger for N implants (up to six orders of magnitude), which are
      shown to introduce stable charged species within the hydrocarbon matrix, not only
      damage as is the case for Ne implants. Fully operational pentacene thin film
      transistors have also been implanted and we show how a controlled N ion
      implantation process can induce stable modifications in the threshold voltage,
      without affecting the device performance.

PMID- 27877852
TI  - Magnetic microparticle-polydimethylsiloxane composite for reversible microchannel
      bonding.
AB  - In this study, an iron oxide magnetic microparticles and poly(dimethylsiloxane)
      (MMPs-PDMS) composite material was employed to demonstrate a simple high-strength
      reversible magnetic bonding method. This paper presents the casting of opaque
      view (where optical inspection through the microchannels was impossible) and
      clear-view (where optical inspection through the microchannel was possible) MMPs
      PDMS. The influence of the microchannel geometries on the casting of the opaque
      view casting was limited, which is similar to standard PDMS casting. Clear-view
      casting performance was highly associated with the microchannel geometries. The
      effects of the microchannel layout and the gap between the PDMS cover layer and
      the micromold substrate were thoroughly investigated. Compared with the native
      PDMS bonding strength of 31 kPa, the MMPs-PDMS magnetic bonding experiments
      showed that the thin PDMS film with an MMPs-PDMS layer effectively reduced the
      surface roughness and enhanced MMPs-PDMS reversible magnetic bonding strength. A
      thin PDMS film-coated opaque-view MMPs-PDMS device exhibited the greatest bonding
      strength of 110 kPa, and a clear-view MMPs-PDMS device with a thin PDMS film
      attained a magnetic bonding strength of 81 kPa.

PMID- 27877853
TI  - Removal of B from Si by Hf addition during Al-Si solvent refining process.
AB  - A small amount of Hf was employed as a new additive to improve B removal in the
      electromagnetic solidification refinement of Si with an Al-Si melt, because Hf
      has a very strong affinity for B. The segregation ratio of Hf between the solid
      Si and Al-Si melt was estimated to range from 4.9 * 10-6 to 8.8 * 10-7 for Al
      concentrations of 0 to 64 at.%, respectively. The activity coefficient of Hf in
      solid Si at its infinite dilution was also estimated. A small addition of Hf
      (<1025 parts per million atoms, ppma) significantly improved the B removal. It
      was confirmed that the use of an increased Hf addition, slower cooling rate, and
      Al-rich Al-Si melt as the refining solvent removed B more efficiently. B in Si
      could be removed as much as 98.2% with 410 ppma Hf addition when the liquidus
      temperature of the Al-Si melt was 1173 K and the cooling rate was 4.5-7.6 K min
      1. The B content in Si could be controlled from 153 ppma to 2.7 ppma, which meets
      the acceptable level for solar-grade Si.

PMID- 27877854
TI  - Silicon etch with chromium ions generated by a filtered or non-filtered cathodic
      arc discharge.
AB  - The pre-treatment of substrate surfaces prior to deposition is important for the
      adhesion of physical vapour deposition coatings. This work investigates Si
      surfaces after the bombardment by energetic Cr ions which are created in cathodic
      arc discharges. The effect of the pre-treatment is analysed by X-ray diffraction,
      Rutherford backscattering spectroscopy, scanning electron microscopy and in-depth
      X-ray photoemission spectroscopy and compared for Cr vapour produced from a
      filtered and non-filtered cathodic arc discharge. Cr coverage as a function of
      ion energy was also predicted by TRIDYN Monte Carlo calculations. Discrepancies
      between measured and simulated values in the transition regime between layer
      growth and surface removal can be explained by the chemical reactions between Cr
      ions and the Si substrate or between the substrate surface and the residual
      gases. Simulations help to find optimum and more stable parameters for specific
      film and substrate combinations faster than trial-and-error procedure.

PMID- 27877855
TI  - Plastic accommodation at homophase interfaces between nanotwinned and
      recrystallized grains in an austenitic duplex-microstructured steel.
AB  - The plastic co-deformation behavior at the homophase interfaces between the hard
      nanotwinned grain inclusions and the soft recrystallized matrix grains in a
      duplex-microstructured AISI 316L austenitic stainless steel is examined through
      the analysis of long-range orientation gradients within the matrix grains by
      electron backscatter diffraction and transmission electron microcopy. Our
      analysis reveals that the mechanical accommodation of homophase interfaces until
      a macroscopic strain of 22% is realized within a small area of soft grains (about
      four grains) adjacent to the homophase interface. The activation of deformation
      twinning in the first two grain layers results in the occurrence of a 'hump' in
      the orientation gradient profile. We ascribe this effect to the role of
      deformation twinning on the generation of geometrically necessary dislocations.
      The smooth profile of the orientation gradient amplitude within the first 10
      grain layers indicates a gradual plastic accommodation of the homophase
      interfaces upon straining. As a consequence, damage nucleation at such interfaces
      is impeded, resulting in an enhanced ductility of the single phase duplex
      microstructured steel.

PMID- 27877856
TI  - A simple synthesis method for nanostructured Co-WC/carbon composites with
      enhanced oxygen reduction reaction activity.
AB  - Co nanoparticles (Co NPs) and nanoscale tungsten carbide (WC) are successfully
      synthesized simultaneously with mesoporous structured carbon black (C) using an
      innovative simple method, which is known as solution plasma processing (SPP), and
      NPs are also loaded onto carbon black at the same time by SPP. The introduction
      of Co NPs led to not only superior oxygen reduction reaction (ORR) activity in
      terms of onset potential and peak potential, but also to a more efficient
      electron transfer process compared to that of pure WC. Co-WC/C also showed
      durability for long-term operation better than that of commercial Pt/C. These
      results clearly demonstrate that the presence of Co NPs significantly enhanced
      the ORR and charge transfer number of neighboring WC NPs in ORR activities. In
      addition, it was proved that SPP is a simple method (from synthesis of NPs and
      carbon black to loading on carbon black) for the large-scale synthesis of NP
      carbon composite. Therefore, SPP holds great potential as a candidate for next
      generation synthetic methods for the production of NP-carbon composites.

PMID- 27877857
TI  - Properties of epitaxial, (001)- and (110)-oriented (PbMg1/3Nb2/3O3)2/3
      (PbTiO3)1/3 films on silicon described by polarization rotation.
AB  - Epitaxial (PbMg1/3Nb2/3O3)2/3-(PbTiO3)1/3 (PMN-PT) films with different out-of
      plane orientations were prepared using a CeO2/yttria stabilized ZrO2 bilayer
      buffer and symmetric SrRuO3 electrodes on silicon substrates by pulsed laser
      deposition. The orientation of the SrRuO3 bottom electrode, either (110) or
      (001), was controlled by the deposition conditions and the subsequent PMN-PT
      layer followed the orientation of the bottom electrode. The ferroelectric,
      dielectric and piezoelectric properties of the (SrRuO3/PMN-PT/SrRuO3)
      ferroelectric capacitors exhibit orientation dependence. The properties of the
      films are explained in terms of a model based on polarization rotation. At low
      applied fields domain switching dominates the polarization change. The model
      indicates that polarization rotation is easier in the (110) film, which is
      ascribed to a smaller effect of the clamping on the shearing of the pseudo-cubic
      unit cell compared to the (001) case.

PMID- 27877858
TI  - Shape-controlled synthesis of porous AuPt nanoparticles and their superior
      electrocatalytic activity for oxygen reduction reaction.
AB  - Control of structure and morphology of Pt-based nanomaterials is of great
      importance for electrochemical energy conversions. In this work, we report an
      efficient one-step synthesis of bimetallic porous AuPt nanoparticles (PAuPt NPs)
      in an aqueous solution. The proposed synthesis is performed by a simple stirring
      treatment of an aqueous reactive mixture including K2PtCl4, HAuCl4, Pluronic F127
      and ascorbic acid at a pH value of 1 without organic solvent or high temperature.
      Due to their porous structure and bimetallic composition, as-made PAuPt NPs
      exhibit excellent electrocatalytic activity for oxygen reduction reaction.

PMID- 27877859
TI  - Self-lubricating, low-friction, wear-resistant Al-based quasicrystalline
      coatings.
AB  - After gas atomization, a quasicrystalline powder based on aluminium was used to
      prepare a thick coating by high-velocity oxygen-fuel flame torch spraying. This
      layer was deposited on top of a bond-coat layer on a steel plate. A post-spraying
      annealing treatment turned the two layers to their stable state, a gamma-brass
      crystal and an icosahedral quasicrystal, respectively. The projection parameters
      were selected in such a way that the coating behaved like a self-lubricating
      material, which offered very good wear resistance (duration of pin-on-disk tests
      superior to 5 km with negligible material loss) and low friction (u <= 6% against
      sintered tungsten carbide), in contrast to the state of the art. This property
      was achieved thanks to, on the one hand, excellent bonding to the substrate via
      the bound coat, and on the other hand, presence at the boundaries between
      quasicrystalline flakes of a mixture of both threefold and fourfold coordinated
      carbon originating from spray processing. Application to hard materials used in
      mechanical devices is appealing, especially because soft, lubricating additives
      may not be needed, thus considerably increasing the lifetime of the devices and
      reducing waste of materials.

PMID- 27877860
TI  - Facile preparation of acid-resistant magnetite particles for removal of Sb(III)
      from strong acidic solution.
AB  - A new facile coating strategy based on the hydrophobicity of methyl groups was
      developed to prevent nano-sized magnetite particles from strong acid corrosion.
      In this method, three steps of hydrolysis led to three layers of protection shell
      coating Fe3O4 nanoparticles. Filled with hydrophobic methyl groups, the middle
      layer mainly prevented the magnetic core from strong acid corrosion. These
      magnetite particles managed to resist 1 M HCl solution and 2.5 M H2SO4 solution.
      The acid resistant ability was higher than those reported previously. After
      further modification with amino-methylene-phosphonic groups, these magnetite
      particles successfully adsorbed Sb(III) in strong acid solution. This new
      strategy can also be applied to protect other materials from strong acid
      corrosion.

PMID- 27877863
TI  - Microstructure study of a severely plastically deformed Mg-Zn-Y alloy by
      application of low angle annular dark field diffraction contrast imaging.
AB  - Microstructural investigation of extremely strained samples, such as severely
      plastically deformed (SPD) materials, by using conventional transmission electron
      microscopy techniques is very challenging due to strong image contrast resulting
      from the high defect density. In this study, low angle annular dark field (LAADF)
      imaging mode of scanning transmission electron microscope (STEM) has been applied
      to study the microstructure of a Mg-3Zn-0.5Y (at%) alloy processed by high
      pressure torsion (HPT). LAADF imaging advantages for observation of twinning,
      grain fragmentation, nucleation of recrystallized grains and precipitation on
      second phase particles in the alloy processed by HPT are highlighted. By using
      STEM-LAADF imaging with a range of incident angles, various microstructural
      features have been imaged, such as nanoscale subgrain structure and
      recrystallization nucleation even from the thicker region of the highly strained
      matrix. It is shown that nucleation of recrystallized grains starts at a strain
      level of revolution [Formula: see text] (earlier than detected by conventional
      bright field imaging). Occurrence of recrystallization of grains by nucleating
      heterogeneously on quasicrystalline particles is also confirmed. Minimizing all
      strain effects by LAADF imaging facilitated grain size measurement of [Formula:
      see text] nm in fully recrystallized HPT specimen after [Formula: see text].

PMID- 27877861
TI  - Fabrication of photoactive heterostructures based on quantum dots decorated with
      Au nanoparticles.
AB  - Silica based multifunctional heterostructures, exhibiting near infrared (NIR)
      absorption (650-1200 nm) and luminescence in the visible region, represent
      innovative nanosystems useful for diagnostic or theranostic applications. Herein,
      colloidal synthetic procedures are applied to design a photoactive
      multifunctional nanosystem. Luminescent silica (SiO2) coated quantum dots (QDs)
      have been used as versatile nanoplatforms to assemble on their surface gold (Au)
      seeds, further grown into Au spackled structures. The synthesized nanostructures
      combine the QD emission in the visible region, and, concomitantly, the
      distinctive NIR absorption of Au nanodomains. The possibility of having multiple
      QDs in a single heterostructure, the SiO2 shell thickness, and the extent of Au
      deposition onto SiO2 surface have been carefully controlled. The work shows that
      a single QD entrapped in 16 nm thick SiO2 shell, coated with Au speckles,
      represents the most suitable geometry to preserve the QD emission in the visible
      region and to generate NIR absorption from metal NPs. The resulting architectures
      present a biomedical potential as an effective optical multimodal probes and as
      promising therapeutic agents due to the Au NP mediated photothermal effect.

PMID- 27877862
TI  - An Ir(III) complex chemosensor for the detection of thiols.
AB  - In this study, we report the use of a cyclometalated luminescent iridium(III)
      complex for the visualization of thiols. The detection of glutathione (GSH) by
      complex 1 is achieved through the reduction of its phendione N^N donor, which
      influences the metal-to-ligand charge-transfer (MLCT) of the complex. Complex 1
      produced a maximum threefold luminescence enhancement at 587 nm in response to
      GSH. The linear detection range of 1 for GSH is between 0.2 and 2 M equivalents
      of GSH, with a detection limit of 1.67 MUM. Complex 1 also displays good
      selectivity for thiols over other amino acids.

PMID- 27877864
TI  - The effect of wall thickness distribution on mechanical reliability and strength
      in unidirectional porous ceramics.
AB  - Macroporous ceramics exhibit an intrinsic strength variability caused by the
      random distribution of defects in their structure. However, the precise role of
      microstructural features, other than pore volume, on reliability is still
      unknown. Here, we analyze the applicability of the Weibull analysis to
      unidirectional macroporous yttria-stabilized-zirconia (YSZ) prepared by ice
      templating. First, we performed crush tests on samples with controlled
      microstructural features with the loading direction parallel to the porosity. The
      compressive strength data were fitted using two different fitting techniques,
      ordinary least squares and Bayesian Markov Chain Monte Carlo, to evaluate whether
      Weibull statistics are an adequate descriptor of the strength distribution. The
      statistical descriptors indicated that the strength data are well described by
      the Weibull statistical approach, for both fitting methods used. Furthermore, we
      assess the effect of different microstructural features (volume, size,
      densification of the walls, and morphology) on Weibull modulus and strength. We
      found that the key microstructural parameter controlling reliability is wall
      thickness. In contrast, pore volume is the main parameter controlling the
      strength. The highest Weibull modulus ([Formula: see text]) and mean strength
      (198.2 MPa) were obtained for the samples with the smallest and narrowest wall
      thickness distribution (3.1 [Formula: see text]m) and lower pore volume (54.5%).

PMID- 27877866
TI  - Unconventional fractional quantum Hall effect in monolayer and bilayer graphene.
AB  - The commensurability condition is applied to determine the hierarchy of
      fractional fillings of Landau levels in monolayer and in bilayer graphene. The
      filling rates for fractional quantum Hall effect (FQHE) in graphene are found in
      the first three Landau levels in one-to-one agreement with the experimental data.
      The presence of even denominator filling fractions in the hierarchy for FQHE in
      bilayer graphene is explained. Experimentally observed hierarchy of FQHE in the
      first and second Landau levels in monolayer graphene and in the zeroth Landau
      level in bilayer graphene is beyond the conventional composite fermion
      interpretation but fits to the presented nonlocal topology commensurability
      condition.

PMID- 27877865
TI  - Three dimensional printed macroporous polylactic acid/hydroxyapatite composite
      scaffolds for promoting bone formation in a critical-size rat calvarial defect
      model.
AB  - We have explored the applicability of printed scaffold by comparing osteogenic
      ability and biodegradation property of three resorbable biomaterials. A
      polylactic acid/hydroxyapatite (PLA/HA) composite with a pore size of 500 MUm and
      60% porosity was fabricated by three-dimensional printing. Three-dimensional
      printed PLA/HA, beta-tricalcium phosphate (beta-TCP) and partially demineralized
      bone matrix (DBM) seeded with bone marrow stromal cells (BMSCs) were evaluated by
      cell adhesion, proliferation, alkaline phosphatase activity and osteogenic gene
      expression of osteopontin (OPN) and collagen type I (COL-1). Moreover, the
      biocompatibility, bone repairing capacity and degradation in three different bone
      substitute materials were estimated using a critical-size rat calvarial defect
      model in vivo. The defects were evaluated by micro-computed tomography and
      histological analysis at four and eight weeks after surgery, respectively. The
      results showed that each of the studied scaffolds had its own specific merits and
      drawbacks. Three-dimensional printed PLA/HA scaffolds possessed good
      biocompatibility and stimulated BMSC cell proliferation and differentiation to
      osteogenic cells. The outcomes in vivo revealed that 3D printed PLA/HA scaffolds
      had good osteogenic capability and biodegradation activity with no difference in
      inflammation reaction. Therefore, 3D printed PLA/HA scaffolds have potential
      applications in bone tissue engineering and may be used as graft substitutes in
      reconstructive surgery.

PMID- 27877867
TI  - Electrical and photo-electrical properties of MoS2 nanosheets with and without an
      Al2O3 capping layer under various environmental conditions.
AB  - The electrical and photo-electrical properties of exfoliated MoS2 were
      investigated in the dark and in the presence of deep ultraviolet (DUV) light
      under various environmental conditions (vacuum, N2 gas, air, and O2 gas). We
      examined the effects of environmental gases on MoS2 flakes in the dark and after
      DUV illumination through Raman spectroscopy and found that DUV light induced red
      and blue shifts of peaks (E12 g and A1 g) position in the presence of N2 and O2
      gases, respectively. In the dark, the threshold voltage in the transfer
      characteristics of few-layer (FL) MoS2 field-effect transistors (FETs) remained
      almost the same in vacuum and N2 gas but shifted toward positive gate voltages in
      air or O2 gas because of the adsorption of oxygen atoms/molecules on the MoS2
      surface. We analyzed light detection parameters such as responsivity,
      detectivity, external quantum efficiency, linear dynamic range, and relaxation
      time to characterize the photoresponse behavior of FL-MoS2 FETs under various
      environmental conditions. All parameters were improved in their performances in
      N2 gas, but deteriorated in O2 gas environment. The photocurrent decayed with a
      large time constant in N2 gas, but decayed with a small time constant in O2 gas.
      We also investigated the characteristics of the devices after passivating by
      Al2O3 film on the MoS2 surface. The devices became almost hysteresis-free in the
      transfer characteristics and stable with improved mobility. Given its outstanding
      performance under DUV light, the passivated device may be potentially used for
      applications in MoS2-based integrated optoelectronic circuits, light sensing
      devices, and solar cells.

PMID- 27877868
TI  - Room-temperature synthesis of three-dimensional porous ZnO@CuNi hybrid magnetic
      layers with photoluminescent and photocatalytic properties.
AB  - A facile synthetic approach to prepare porous ZnO@CuNi hybrid films is presented.
      Initially, magnetic CuNi porous layers (consisting of phase separated CuNi
      alloys) are successfully grown by electrodeposition at different current
      densities using H2 bubbles as a dynamic template to generate the porosity. The
      porous CuNi alloys serve as parent scaffolds to be subsequently filled with a
      solution containing ZnO nanoparticles previously synthesized by sol-gel. The
      dispersed nanoparticles are deposited dropwise onto the CuNi frameworks and the
      solvent is left to evaporate while the nanoparticles impregnate the interior of
      the pores, rendering ZnO-coated CuNi 3D porous structures. No thermal annealing
      is required to obtain the porous films. The synthesized hybrid porous layers
      exhibit an interesting combination of tunable ferromagnetic and photoluminescent
      properties. In addition, the aqueous photocatalytic activity of the composite is
      studied under UV-visible light irradiation for the degradation of Rhodamine B.
      The proposed method represents a fast and inexpensive approach towards the
      implementation of devices based on metal-semiconductor porous systems, avoiding
      the use of post-synthesis heat treatment steps which could cause deleterious
      oxidation of the metallic counterpart, as well as collapse of the porous
      structure and loss of the ferromagnetic properties.

PMID- 27877870
TI  - Luminescence of delafossite-type CuAlO2 fibers with Eu substitution for Al
      cations.
AB  - CuAlO2 has been examined as a potential luminescent material by substituting Eu
      for Al cations in the delafossite structure. CuAlO2:Eu3+ nanofibers have been
      prepared via electrospinning for the ease of mitigating synthesis requirements
      and for future optoelectronics and emerging applications. Single-phase CuAlO2
      fibers could be obtained at a temperature of 1100  degrees C in air. The Eu was
      successfully doped in the delafossite structure and two strong emission bands at
      ~405 and 610 nm were observed in the photoluminescence spectra. These bands are
      due to the intrinsic near-band-edge transition of CuAlO2 and the f-f transition
      of the Eu3+ activator, respectively. Further electrical characterization
      indicated that these fibers exhibit semiconducting behavior and the introduction
      of Eu could act as band-edge modifiers, thus changing the thermal activation
      energies. In light of this study, CuAlO2:Eu3+ fibers with both strong
      photoluminescence and p-type conductivity could be produced by tailoring the rare
      earth doping concentrations.

PMID- 27877869
TI  - Experimental study and modeling of atomic-scale friction in zigzag and armchair
      lattice orientations of MoS2.
AB  - Physical properties of two-dimensional materials, such as graphene, black
      phosphorus, molybdenum disulfide (MoS2) and tungsten disulfide, exhibit
      significant dependence on their lattice orientations, especially for zigzag and
      armchair lattice orientations. Understanding of the atomic probe motion on
      surfaces with different orientations helps in the study of anisotropic materials.
      Unfortunately, there is no comprehensive model that can describe the probe motion
      mechanism. In this paper, we report a tribological study of MoS2 in zigzag and
      armchair orientations. We observed a characteristic power spectrum and friction
      force values. To explain our results, we developed a modified, two-dimensional,
      stick-slip Tomlinson model that allows simulation of the probe motion on MoS2
      surfaces by combining the motion in the Mo layer and S layer. Our model fits well
      with the experimental data and provides a theoretical basis for tribological
      studies of two-dimensional materials.

PMID- 27877871
TI  - Modeling of metastable phase formation diagrams for sputtered thin films.
AB  - A method to model the metastable phase formation in the Cu-W system based on the
      critical surface diffusion distance has been developed. The driver for the
      formation of a second phase is the critical diffusion distance which is dependent
      on the solubility of W in Cu and on the solubility of Cu in W. Based on
      comparative theoretical and experimental data, we can describe the relationship
      between the solubilities and the critical diffusion distances in order to model
      the metastable phase formation. Metastable phase formation diagrams for Cu-W and
      Cu-V thin films are predicted and validated by combinatorial magnetron sputtering
      experiments. The correlative experimental and theoretical research strategy
      adopted here enables us to efficiently describe the relationship between the
      solubilities and the critical diffusion distances in order to model the
      metastable phase formation during magnetron sputtering.

PMID- 27877872
TI  - Study of {332}<113> twinning in a multilayered Ti-10Mo-xFe (x = 1-3) alloy by
      ECCI and EBSD.
AB  - We have investigated the propagation of {332}<113> twins in a multilayered Ti
      10Mo-xFe (x = 1-3) alloy fabricated by multi-pass hot rolling. The material
      contains a macroscopic Fe-graded structure (about 130 MUm width) between 1 and 3
      wt% Fe in the direction perpendicular to rolling. We observe strong influence of
      the Fe-graded structure in the twin propagation behavior. The propagation of
      {332}<113> twins that are nucleated in Fe-lean regions (~1 wt% Fe) is interrupted
      in the grain interiors at a specific Fe content, namely, about 2 wt% Fe. We
      ascribe this effect to the role of Fe content in solid solution on the stress for
      twin propagation. The interruption of twins in the grain interiors results in the
      development of characteristic dislocation configurations such as highly dense
      dislocation walls (HDDWs) associated to strain localization phenomena. The
      nucleation and propagation of these dislocation configurations is ascribed to the
      underlying plastic accommodation mechanisms of the stress field at the twin tips.
      We find that the crystallographic alignment of HDDWs is determined by the stress
      field at the twin tips and the deformation texture. The excellent plastic
      accommodation at the interrupted twin tips allows attaining the good ductility of
      the present material (total elongation of 28%).

PMID- 27877873
TI  - Preparation of magnetic mesoporous silica nanoparticles as a multifunctional
      platform for potential drug delivery and hyperthermia.
AB  - We report the preparation of magnetic mesoporous silica (MMS) nanoparticles with
      the potential multifunctionality of drug delivery and magnetic hyperthermia.
      Carbon-encapsulated magnetic colloidal nanoparticles (MCN@C) were used to coat
      mesoporous silica shells for the formation of the core-shell structured MMS
      nanoparticles (MCN@C/mSiO2), and the rattle-type structured MMS nanoparticles
      (MCN/mSiO2) were obtained after the removal of the carbon layers from MCN@C/mSiO2
      nanoparticles. The morphology, structure, magnetic hyperthermia ability, drug
      release behavior, in vitro cytotoxicity and cellular uptake of MMS nanoparticles
      were investigated. The results revealed that the MCN@C/mSiO2 and MCN/mSiO2
      nanoparticles had spherical morphology and average particle sizes of 390 and 320
      nm, respectively. The MCN@C/mSiO2 nanoparticles exhibited higher magnetic
      hyperthermia ability compared to the MCN/mSiO2 nanoparticles, but the MCN/mSiO2
      nanoparticles had higher drug loading capacity. Both MCN@C/mSiO2 and MCN/mSiO2
      nanoparticles had similar drug release behavior with pH-controlled release and
      temperature-accelerated release. Furthermore, the MCN@C/mSiO2 and MCN/mSiO2
      nanoparticles showed low cytotoxicity and could be internalized into HeLa cells.
      Therefore, the MCN@C/mSiO2 and MCN/mSiO2 nanoparticles would be promising for the
      combination of drug delivery and magnetic hyperthermia treatment in cancer
      therapy.

PMID- 27877874
TI  - Growth condition dependence of unintentional oxygen incorporation in epitaxial
      GaN.
AB  - Growth conditions have a tremendous impact on the unintentional background
      impurity concentration in gallium nitride (GaN) synthesized by molecular beam
      epitaxy and its resulting chemical and physical properties. In particular for
      oxygen identified as the dominant background impurity we demonstrate that under
      optimized growth stoichiometry the growth temperature is the key parameter to
      control its incorporation and that an increase by 55  degrees C leads to an
      oxygen reduction by one order of magnitude. Quantitatively this reduction and the
      resulting optical and electrical properties are analyzed by secondary ion mass
      spectroscopy, photoluminescence, capacitance versus voltage measurements, low
      temperature magneto-transport and parasitic current paths in lateral transistor
      test structures based on two-dimensional electron gases. At a growth temperature
      of 665  degrees C the residual charge carrier concentration is decreased to below
      1015 cm-3, resulting in insulating behavior and thus making the material suitable
      for beyond state-of-the-art device applications.

PMID- 27877875
TI  - Focus on nanomedicine molecular science.

PMID- 27877876
TI  - Enhanced cellular uptake of lactosomes using cell-penetrating peptides.
AB  - Polymeric micelles that are composed of synthetic polymers are generally size
      controllable and can be easily modified for various applications. Lactosomes (A3B
      type) are biodegradable polymeric micelles composed of an amphipathic polymer,
      including three poly(sarcosine) blocks and a poly(l-lactic acid) block.
      Lactosomes accumulate in tumors in vivo through the enhanced permeability and
      retention (EPR) effect, even on frequently administering them. However,
      lactosomes cannot be efficiently internalized by cells. To improve cellular
      uptake of lactosomes, cell-penetrating peptide (CPP)-modified lactosomes were
      prepared. Seven CPPs (including EB1 and Pep1) were used, and most of them
      improved the cellular uptake efficiency of lactosomes. In particular, EB1- and
      Pep1-modified lactosomes were efficiently internalized by cells. In addition, by
      using CPP-modified and photosensitizer-loaded lactosomes, we demonstrated the
      photoinduced killing of mammalian cells, including human cancer cells.
      Accumulation of the EB1-modified lactosomes in NCI-N87 tumors was shown by in
      vivo imaging. Thus, this study demonstrated that the CPP-modified lactosome is a
      promising drug carrier.

PMID- 27877877
TI  - Materials inspired by mathematics.
AB  - Our world is transforming into an interacting system of the physical world and
      the digital world. What will be the materials science in the new era? With the
      rising expectations of the rapid development of computers, information science
      and mathematical science including statistics and probability theory, 'data
      driven materials design' has become a common term. There is knowledge and
      experience gained in the physical world in the form of know-how and recipes for
      the creation of material. An important key is how we establish vocabulary and
      grammar to translate them into the language of the digital world. In this
      article, we outline how materials science develops when it encounters
      mathematics, showing some emerging directions.

PMID- 27877878
TI  - A transparent, solvent-free laminated top electrode for perovskite solar cells.
AB  - A simple lamination process of the top electrode for perovskite solar cells is
      demonstrated. The laminate electrode consists of a transparent and conductive
      plastic/metal mesh substrate, coated with an adhesive mixture of poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate), PEDOT:PSS, and sorbitol. The
      laminate electrode showed a high degree of transparency of 85%. Best cell
      performance was achieved for laminate electrodes prepared with a sorbitol
      concentration of ~30 wt% per milliliter PEDOT:PSS dispersion, and using a pre
      annealing temperature of 120 degrees C for 10 min before lamination. Thereby,
      perovskite solar cells with stabilized power conversion efficiencies of (7.6 +/-
      1.0)% were obtained which corresponds to 80% of the reference devices with
      reflective opaque gold electrodes.

PMID- 27877879
TI  - A stem-less probe using spontaneous pairing between Cy3 and quencher for RNA
      detection.
AB  - We herein report a stem-less probe for the detection of RNA that depends on
      pairing between Cy3 and nitro methyl red. In our design, two Cy3 residues and two
      nitro methyl red residues were introduced into an oligonucleotide. In the absence
      of the target, these dyes formed a complex, and emission of Cy3 was efficiently
      quenched. Hybridization with the target RNA disrupted this interaction and
      resulted in Cy3 emission. Under optimized conditions, the signal to background
      ratio was as high as 180. We demonstrated specific detection of target RNA in
      cells using a wash-free FISH protocol.

PMID- 27877880
TI  - NEXAFS study of electronic and atomic structure of active layer in Al/indium tin
      oxide/TiO2 stack during resistive switching.
AB  - We have studied the stability of the resistive switching process in the
      Al/(In2O3)0.9(SnO2)0.1/TiO2 assembly grown by atomic layer deposition. Besides
      electrical characterization the effect of electric field on the atomic electronic
      structure of the TiO2 layer was studied using near edge X-ray absorption fine
      structure (NEXAFS) spectroscopy. The region of the current instability in the I-V
      characteristics was revealed. Presumably this current instability is supported by
      the amorphous structure of the TiO2 film but is initiated by the surface
      morphology of the Al substrate. A formation of the O2 molecules was established
      which occurs specifically in the region of the current instability that is a
      result of electrical Joule heating manifestation.

PMID- 27877881
TI  - Crosslinked duplex DNA nanogels that target specified proteins.
AB  - Specific detection of protein biomarkers plays an important role in diagnostics
      and therapeutics. We have fabricated polymeric nanogels, which can specifically
      interact with the cancer biomarker thrombin to serve as a model. Two types of 2
      methacryloyloxyethyl phosphorylcholine (MPC) copolymers bearing a thrombin
      binding oligonucleotide aptamer and its complementary chain were independently
      synthesized by redox-initiated radical polymerization. These MPC polymers
      associate in a complimentary fashion due to double strand formation of the
      oligonucleotides in aqueous media, leading to the spontaneous formation of
      spherical nanogels. Nanogel formation was confirmed by dynamic light scattering
      (DLS) and transmittance microscopy. The average size of nanogel particles was 124
      +/- 2 nm and the nanogels were mono-dispersed (polydispersity index 0.21).
      Functional intercalators could be stably incorporated into nanogels through the
      physical interaction between the intercalators and the oligonucleotides. The
      ethidium bromide (EtBr)-incorporating nanogels were used as detectors for
      thrombin. The fluorescence intensity of solutions containing the EtBr
      incorporating nanogels was decreased with an increase in the concentration of
      thrombin. The transformation of quadruplex-thrombin structure from complementary
      double-stranded structures resulted in the decrease in fluorescence intensity. In
      contrast, the intensity did not change when the nanogels were incubated with
      albumin. Thrombin is only one such model used to demonstrate this technique;
      oligonucleotide aptamers can be freely designed to interact with versatile bio
      substances. Therefore, aptamer-crosslinked nanogels can be appropriate
      nanomaterials for disease diagnosis and therapy.

PMID- 27877882
TI  - Focal calcium monitoring with targeted nanosensors at the cytosolic side of
      endoplasmic reticulum.
AB  - Ca2+ distribution is spatially and temporally non-uniform inside cells due to
      cellular compartmentalization. However, Ca2+ sensing with small organic dyes,
      such as fura-2 and fluo-4, has been practically applied at a single cell level
      where the averaged signal from freely diffusing dye molecules is acquired. In
      this study, we aimed to target azide-functionalized fura-2 (N3-fura-2) to a
      specific site of subcellular compartments to realize focal Ca2+ sensing. Using
      scAVD (single-chain avidin)-biotin interaction and a copper-free click reaction
      system, we linked N3-fura-2 to specifically-targeted scAVD protein fused with a
      red fluorescent protein mCherry, so that Ca2+ sensors conjugated with four N3
      fura-2 dyes with dibenzocyclooctyne (DBCO)-PEG4-biotin as a linker were generated
      at subcellular compartments in living cells. In cytoplasm, N3-fura-2 showed a
      prolonged retention period after binding to scAVD. Furthermore, the reacted N3
      fura-2 was retained inside cells even after free dyes were washed out by methanol
      fixation. When scAVD was overexpressed on endoplasmic reticulum (ER) membranes,
      N3-fura-2 was accumulated on ER membranes. Upon histamine stimulation, which
      increases cytosolic Ca2+ concentration, ER-localized N3-fura-2 successfully
      sensed the Ca2+ level changes at the cytosolic side of ER membrane. Our study
      demonstrated specific targeting of N3-fura-2 to subcellular compartments and the
      ability of sensing focal Ca2+ level changes with the specifically targeted Ca2+
      sensors.

PMID- 27877884
TI  - Gas permeability of ice-templated, unidirectional porous ceramics.
AB  - We investigate the gas flow behavior of unidirectional porous ceramics processed
      by ice-templating. The pore volume ranged between 54% and 72% and pore size
      between 2.9 [Formula: see text]m and 19.1 [Formula: see text]m. The maximum
      permeability ([Formula: see text] [Formula: see text] m[Formula: see text]) was
      measured in samples with the highest total pore volume (72%) and pore size (19.1
      [Formula: see text]m). However, we demonstrate that it is possible to achieve a
      similar permeability ([Formula: see text] [Formula: see text] m[Formula: see
      text]) at 54% pore volume by modification of the pore shape. These results were
      compared with those reported and measured for isotropic porous materials
      processed by conventional techniques. In unidirectional porous materials
      tortuosity ([Formula: see text]) is mainly controlled by pore size, unlike in
      isotropic porous structures where [Formula: see text] is linked to pore volume.
      Furthermore, we assessed the applicability of Ergun and capillary model in the
      prediction of permeability and we found that the capillary model accurately
      describes the gas flow behavior of unidirectional porous materials. Finally, we
      combined the permeability data obtained here with strength data for these
      materials to establish links between strength and permeability of ice-templated
      materials.

PMID- 27877883
TI  - Cytocompatible and multifunctional polymeric nanoparticles for transportation of
      bioactive molecules into and within cells.
AB  - Multifunctional polymeric nanoparticles are materials with great potential for a
      wide range of biomedical applications. For progression in this area of research,
      unfavorable interactions of these nanoparticles with proteins and cells must be
      avoided in biological environments, for example, through treatment of the
      nanoparticle surfaces. Construction of an artificial cell membrane structure
      based on polymers bearing the zwitterionic phosphorylcholine group can prevent
      biological reactions at the surface effectively. In addition, certain bioactive
      molecules can be immobilized on the surface of the polymer to generate enough
      affinity to capture target biomolecules. Furthermore, entrapment of inorganic
      nanoparticles inside polymeric matrices enhances the nanoparticle functionality
      significantly. This review summarizes the preparation and characterization of
      cytocompatible and multifunctional polymeric nanoparticles; it analyzes the
      efficiency of their fluorescence function, the nature of the artificial cell
      membrane structure, and their performance as in-cell devices; and finally, it
      evaluates both their chemical reactivity and effects in cells.

PMID- 27877885
TI  - Investigation of microstructure in additive manufactured Inconel 625 by spatially
      resolved neutron transmission spectroscopy.
AB  - Non-destructive testing techniques based on neutron imaging and diffraction can
      provide information on the internal structure of relatively thick metal samples
      (up to several cm), which are opaque to other conventional non-destructive
      methods. Spatially resolved neutron transmission spectroscopy is an extension of
      traditional neutron radiography, where multiple images are acquired
      simultaneously, each corresponding to a narrow range of energy. The analysis of
      transmission spectra enables studies of bulk microstructures at the spatial
      resolution comparable to the detector pixel. In this study we demonstrate the
      possibility of imaging (with ~100 MUm resolution) distribution of some
      microstructure properties, such as residual strain, texture, voids and impurities
      in Inconel 625 samples manufactured with an additive manufacturing method called
      direct metal laser melting (DMLM). Although this imaging technique can be
      implemented only in a few large-scale facilities, it can be a valuable tool for
      optimization of additive manufacturing techniques and materials and for
      correlating bulk microstructure properties to manufacturing process parameters.
      In addition, the experimental strain distribution can help validate finite
      element models which many industries use to predict the residual stress
      distributions in additive manufactured components.

PMID- 27877886
TI  - Oleyl group-functionalized insulating gate transistors for measuring
      extracellular pH of floating cells.
AB  - The extracellular ionic microenvironment has a close relationship to biological
      activities such as by cellular respiration, cancer development, and immune
      response. A system composed of ion-sensitive field-effect transistors (ISFET),
      cells, and program-controlled fluidics has enabled the acquisition of real-time
      information about the integrity of the cell membrane via pH measurement. Here we
      aimed to extend this system toward floating cells such as T lymphocytes for
      investigating complement activation and pharmacokinetics through alternations in
      the plasma membrane integrity. We functionalized the surface of tantalum oxide
      gate insulator of ISFET with oleyl-tethered phosphonic acid for interacting with
      the plasma membranes of floating cells without affecting the cell signaling. The
      surface modification was characterized by X-ray photoelectron spectroscopy and
      water contact angle measurements. The Nernst response of -37.8 mV/pH was obtained
      for the surface-modified ISFET at 37  degrees C. The oleyl group-functionalized
      gate insulator successfully captured Jurkat T cells in a fluidic condition
      without acute cytotoxicity. The system was able to record the time course of pH
      changes at the cells/ISFET interface during the process of instant addition and
      withdrawal of ammonium chloride. Further, the plasma membrane injury of floating
      cells after exposure by detergent TritonTM X-100 was successfully determined
      using the modified ISFET with enhanced sensitivity as compared with conventional
      hemolysis assays.

PMID- 27877887
TI  - In vitro biomechanical properties, fluorescence imaging, surface-enhanced Raman
      spectroscopy, and photothermal therapy evaluation of luminescent functionalized
      CaMoO4:Eu@Au hybrid nanorods on human lung adenocarcinoma epithelial cells.
AB  - Highly dispersible Eu3+-doped CaMoO4@Au-nanorod hybrid nanoparticles (HNPs)
      exhibit optical properties, such as plasmon resonances in the near-infrared
      region at 790 nm and luminescence at 615 nm, offering multimodal capabilities:
      fluorescence imaging, surface-enhanced Raman spectroscopy (SERS) detection and
      photothermal therapy (PTT). HNPs were conjugated with a Raman reporter (4
      mercaptobenzoic acid), showing a desired SERS signal (enhancement factor 5.0 *
      105). The HNPs have a heat conversion efficiency of 25.6%, and a hyperthermia
      temperature of 42 degrees C could be achieved by adjusting either concentration
      of HNPs, or laser power, or irradiation time. HNPs were modified with antibody
      specific to cancer biomarker epidermal growth factor receptor, then applied to
      human lung cancer (A549) and mouse hepatocyte cells (AML12), and in vitro PTT
      effect was studied. In addition, the biomechanical properties of A549 cells were
      quantified using atomic force microscopy. This study shows the potential
      applications of these HNPs in fluorescence imaging, SERS detection, and PTT with
      good photostability and biocompatibility.

PMID- 27877888
TI  - Lysosomal pH-inducible supramolecular dissociation of polyrotaxanes possessing
      acid-labile N-triphenylmethyl end groups and their therapeutic potential for
      Niemann-Pick type C disease.
AB  - Niemann-Pick type C (NPC) disease is characterized by the accumulation of
      cholesterol in lysosomes. We have previously reported that biocleavable
      polyrotaxanes (PRXs) composed of beta-cyclodextrins (beta-CDs) threaded onto a
      linear polymer capped with bulky stopper molecules via intracellularly cleavable
      linkers show remarkable cholesterol reducing effects in NPC disease patient
      derived fibroblasts owing to the stimuli-responsive intracellular dissociation of
      PRXs and subsequent beta-CD release from the PRXs. Herein, we describe a series
      of novel acid-labile 2-(2-hydroxyethoxy)ethyl group-modified PRXs (HEE-PRXs)
      bearing terminal N-triphenylmethyl (N-Trt) groups as a cleavable component for
      the treatment of NPC disease. The N-Trt end groups of the HEE-PRXs underwent
      acidic pH-induced cleavage and led to the dissociation of their supramolecular
      structure. A kinetic study revealed that the number of HEE groups on the PRX did
      not affect the cleavage kinetics of the N-Trt end groups of the HEE-PRXs. The
      effect of the number of HEE groups of the HEE-PRXs, which was modified to impart
      water solubility to the PRXs, on cellular internalization efficiency, lysosomal
      localization efficiency, and cholesterol reduction ability in NPC disease-derived
      fibroblasts (NPC1 fibroblasts) was also investigated. The cellular uptake and
      lysosomal localization efficiency were almost equivalent for HEE-PRXs with
      different numbers of HEE groups. However, the cholesterol reducing ability of the
      HEE-PRXs in NPC1 fibroblasts was affected by the number of HEE groups, and HEE
      PRXs with a high number of HEE groups were unable to reduce lysosomal cholesterol
      accumulation. This deficiency is most likely due to the cholesterol-solubilizing
      ability of HEE-modified beta-CDs released from the HEE-PRXs. We conclude that the
      N-Trt group acts as a cleavable component to induce the lysosomal dissociation of
      HEE-PRXs, and acid-labile HEE-PRXs with an optimal number of HEE groups (4.1 to
      5.4 HEE groups per single beta-CD threaded onto the PRX) have great therapeutic
      potential for treating NPC disease.

PMID- 27877889
TI  - Facile synthesis of reduced graphene oxide-gold nanohybrid for potential use in
      industrial waste-water treatment.
AB  - Here, we report a facile approach, by the photochemical reduction technique, for
      in situ synthesis of Au-reduced graphene oxide (Au-RGO) nanohybrids, which
      demonstrate excellent adsorption capacities and recyclability for a broad range
      of dyes. High-resolution transmission electron microscopy (HRTEM), X-ray
      diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) data confirm the
      successful synthesis of Au-RGO nanohybrids. The effect of several experimental
      parameters (temperature and pH) variation can effectively control the dye
      adsorption capability. Furthermore, kinetic adsorption data reveal that the
      adsorption process follows a pseudo second-order model. The negative value of
      Gibbs free energy (DeltaG0) confirms spontaneity while the positive enthalpy
      (DeltaH0) indicates the endothermic nature of the adsorption process. Picosecond
      resolved fluorescence technique unravels the excited state dynamical processes of
      dye molecules adsorbed on the Au-RGO surface. Time resolved fluorescence
      quenching of Rh123 after adsorption on Au-RGO nanohybrids indicates efficient
      energy transfer from Rh123 to Au nanoparticles. A prototype device has been
      fabricated using Au-RGO nanohybrids on a syringe filter (pore size: 0.220 MUm)
      and the experimental data indicate efficient removal of dyes from waste water
      with high recyclability. The application of this nanohybrid may lead to the
      development of an efficient reusable adsorbent in portable water purification.

PMID- 27877890
TI  - X-ray computed tomography imaging of a tumor with high sensitivity using gold
      nanoparticles conjugated to a cancer-specific antibody via polyethylene glycol
      chains on their surface.
AB  - Contrast agents are often used to enhance the contrast of X-ray computed
      tomography (CT) imaging of tumors to improve diagnostic accuracy. However,
      because the iodine-based contrast agents currently used in hospitals are of low
      molecular weight, the agent is rapidly excreted from the kidney or moves to
      extravascular tissues through the capillary vessels, depending on its
      concentration gradient. This leads to nonspecific enhancement of contrast images
      for tissues. Here, we created gold (Au) nanoparticles as a new contrast agent to
      specifically image tumors with CT using an enhanced permeability and retention
      (EPR) effect. Au has a higher X-ray absorption coefficient than does iodine. Au
      nanoparticles were supported with polyethylene glycol (PEG) chains on their
      surface to increase the blood retention and were conjugated with a cancer
      specific antibody via terminal PEG chains. The developed Au nanoparticles were
      injected into tumor-bearing mice, and the distribution of Au was examined with CT
      imaging, transmission electron microscopy, and elemental analysis using
      inductively coupled plasma optical emission spectrometry. The results show that
      specific localization of the developed Au nanoparticles in the tumor is affected
      by a slight difference in particle size and enhanced by the conjugation of a
      specific antibody against the tumor.

PMID- 27877891
TI  - Bloch surface wave structures for high sensitivity detection and compact
      waveguiding.
AB  - Resonant propagating waves created on the surface of a dielectric multilayer
      stack, called Bloch surface waves (BSW), can be designed for high sensitivity
      monitoring of the adjacent refractive index as an alternative platform to the
      metal-based surface plasmon resonance (SPR) sensing. The resonant wavelength and
      polarization can be designed by engineering of the dielectric layers unlike the
      fixed resonance of SPR, while the wide bandwidth low loss of dielectrics permits
      sharper resonances, longer propagation lengths and thus their use in waveguiding
      devices. The transparency of the dielectrics allows the excitation and monitoring
      of surface-bound fluorescent molecules. We review the recent developments in this
      technology. We show the advantages that can be obtained by using high index
      contrast layered structures. Operating at 1550 nm wavelengths will allow the BSW
      sensors to be implemented in the silicon photonics platform where active
      waveguiding can be used in the realization of compact planar integrated circuits
      for multi-parameter sensing.

PMID- 27877892
TI  - Towards a metadata scheme for the description of materials - the description of
      microstructures.
AB  - The property of any material is essentially determined by its microstructure.
      Numerical models are increasingly the focus of modern engineering as helpful
      tools for tailoring and optimization of custom-designed microstructures by
      suitable processing and alloy design. A huge variety of software tools is
      available to predict various microstructural aspects for different materials. In
      the general frame of an integrated computational materials engineering (ICME)
      approach, these microstructure models provide the link between models operating
      at the atomistic or electronic scales, and models operating on the macroscopic
      scale of the component and its processing. In view of an improved
      interoperability of all these different tools it is highly desirable to establish
      a standardized nomenclature and methodology for the exchange of microstructure
      data. The scope of this article is to provide a comprehensive system of metadata
      descriptors for the description of a 3D microstructure. The presented descriptors
      are limited to a mere geometric description of a static microstructure and have
      to be complemented by further descriptors, e.g. for properties, numerical
      representations, kinetic data, and others in the future. Further attributes to
      each descriptor, e.g. on data origin, data uncertainty, and data validity range
      are being defined in ongoing work. The proposed descriptors are intended to be
      independent of any specific numerical representation. The descriptors defined in
      this article may serve as a first basis for standardization and will simplify the
      data exchange between different numerical models, as well as promote the
      integration of experimental data into numerical models of microstructures. An
      HDF5 template data file for a simple, three phase Al-Cu microstructure being
      based on the defined descriptors complements this article.

PMID- 27877893
TI  - Latent pH-responsive ratiometric fluorescent cluster based on self-assembled
      photoactivated SNARF derivatives.
AB  - We have developed a self-assembled fluorescent cluster comprising a
      seminaphthorhodafluor (SNARF) derivative protected by a photoremovable o
      nitrobenzyl group. Prior to UV irradiation, a colorless and nonfluorescent
      cluster was spontaneously assembled in aqueous solution. After UV irradiation,
      the self-assembled cluster remained intact and showed a large enhancement in pH
      responsive fluorescence. The unique pH responsive fluorescent cluster could be
      used as a dual-emissive ratiometric fluorescent pH probe not only in the test
      tube but also in HeLa cell cultures.

PMID- 27877894
TI  - Cooperative enhancement of deoxyribozyme activity by chemical modification and
      added cationic copolymer.
AB  - Deoxyribozymes (DNAzymes) having RNA-cleaving activity have widely been explored
      as tools for therapeutic and diagnostic purposes. Both the chemical cleaving step
      and the turnover step should be improved for enhancing overall activity of
      DNAzymes. We have shown that cationic copolymer enhanced DNAzyme activity by
      increasing turnover efficacy. In this paper, effects of the copolymer on DNAzymes
      modified with locked nucleic acids (LNA) or 2'-O-methylated (2'-OMe) nucleic
      acids were studied. The copolymer increased activity of these chemically modified
      DNAzymes. More than 30-fold enhancement in multiple-turnover catalytic activity
      was observed with 2'-OMe-modified DNAzyme in the presence of the copolymer.
      DNAzyme catalytic activity was successfully enhanced by cooperation of the added
      copolymer and chemical modification of DNAzyme.

PMID- 27877896
TI  - Magnetization reversal and microstructure in polycrystalline Fe50Pd50 dot arrays
      by self-assembling of polystyrene nanospheres.
AB  - Nanoscale magnetic materials are the basis of emerging technologies to develop
      novel magnetoelectronic devices. Self-assembly of polystyrene nanospheres is here
      used to generate 2D hexagonal dot arrays on Fe50Pd50 thin films. This simple
      technique allows a wide-area patterning of a magnetic thin film. The role of
      disorder on functional magnetic properties with respect to conventional
      lithographic techniques is studied. Structural and magnetic characteristics have
      been investigated in arrays having different geometry (i.e. dot diameters, inter
      dot distances and thickness). The interplay among microstructure and
      magnetization reversal is discussed. Magnetic measurements reveal a vortex domain
      configuration in all as-prepared films. The original domain structure changes
      drastically upon thermal annealing performed to promote the transformation of
      disordered A1 phase into the ordered, tetragonal L10 phase. First-order reversal
      magnetization curves have been measured to rule out the role of magnetic
      interaction among crystalline phases characterized by different magnetic
      coercivity.

PMID- 27877895
TI  - Visible tunable lighting system based on polymer composites embedding ZnO and
      metallic clusters: from colloids to thin films.
AB  - The development of phosphor devices free of heavy metal or rare earth elements is
      an important issue for environmental reasons and energy efficiency. Different
      mixtures of ZnO nanocrystals with Cs2Mo6I8(OOC2F5)6 cluster compound (CMIF)
      dispersed into polyvinylpyrrolidone matrix have been prepared by very simple and
      low cost solution chemistry. The resulting solutions have been used to fabricate
      highly transparent and luminescent films by dip coating free of heavy metal or
      rare earth elements. The luminescence properties of solution and dip-coated films
      were investigated. The luminescence of such a system is strongly dependent on the
      ratios between ZnO and CMIF amounts, the excitation wavelength and the nature of
      the system. By varying these two parameters (ratio and wavelength), a large
      variety of colors, from blue to red as well as white, can be achieved. In
      addition, differences in the luminescence properties have been observed between
      solutions and thin films as well as changes of CMIF emission band maximum
      wavelength. This may suggest some possible interactions between the different
      luminophore centers, such as energy transfer or ligands exchange on the Mo6
      clusters.

PMID- 27877897
TI  - Quantitative evaluation of malignant gliomas damage induced by photoactivation of
      IR700 dye.
AB  - The processes involved in malignant gliomas damage were quantitatively evaluated
      by microscopy. The near-infrared fluorescent dye IR700 that is conjugated to an
      anti-CD133 antibody (IR700-CD133) specifically targets malignant gliomas (U87MG)
      and stem cells (BT142) and is endocytosed into the cells. The gliomas are then
      photodamaged by the release of reactive oxygen species (ROS) and the heat induced
      by illumination of IR700 by a red laser, and the motility of the vesicles within
      these cells is altered as a result of cellular damage. To investigate these
      changes in motility, we developed a new method that measures fluctuations in the
      intensity of phase-contrast images obtained from small areas within cells. The
      intensity fluctuation in U87MG cells gradually decreased as cell damage
      progressed, whereas the fluctuation in BT142 cells increased. The endocytosed
      IR700 dye was co-localized in acidic organelles such as endosomes and lysosomes.
      The pH in U87MG cells, as monitored by a pH indicator, was decreased and then
      gradually increased by the illumination of IR700, while the pH in BT142 cells
      increased monotonically. In these experiments, the processes of cell damage were
      quantitatively evaluated according to the motility of vesicles and changes in pH.

PMID- 27877898
TI  - Nanoporous carbon materials with enhanced supercapacitance performance and non
      aromatic chemical sensing with C1/C2 alcohol discrimination.
AB  - We have investigated the textural properties, electrochemical supercapacitances
      and vapor sensing performances of bamboo-derived nanoporous carbon materials
      (NCM). Bamboo, an abundant natural biomaterial, was chemically activated with
      phosphoric acid at 400  degrees C and the effect of impregnation ratio of
      phosphoric acid on the textural properties and electrochemical performances was
      systematically investigated. Fourier transform-infrared (FTIR) spectroscopy
      confirmed the presence of various oxygen-containing surface functional groups
      (i.e. carboxyl, carboxylate, carbonyl and phenolic groups) in NCM. The prepared
      NCM are amorphous in nature and contain hierarchical micropores and mesopores.
      Surface areas and pore volumes were found in the range 218-1431 m2 g-1 and 0.26
      1.26 cm3 g-1, respectively, and could be controlled by adjusting the impregnation
      ratio of phosphoric acid and bamboo cane powder. NCM exhibited electrical double
      layer supercapacitor behavior giving a high specific capacitance of c.256 F g-1
      at a scan rate of 5 mV s-1 together with high cyclic stability with capacitance
      retention of about 92.6% after 1000 cycles. Furthermore, NCM exhibited excellent
      vapor sensing performance with high sensitivity for non-aromatic chemicals such
      as acetic acid. The system would be useful to discriminate C1 and C2 alcohol
      (methanol and ethanol).

PMID- 27877900
TI  - Plastic deformation of directionally solidified ingots of binary and some ternary
      MoSi2/Mo5Si3 eutectic composites.
AB  - The high-temperature mechanical properties of directionally solidified (DS)
      ingots of binary and some ternary MoSi2/Mo5Si3 eutectic composites with a script
      lamellar structure have been investigated as a function of loading axis
      orientation and growth rate in a temperature range from 900 to 1500 degrees C.
      These DS ingots are plastically deformed above 1000 and 1100  degrees C when the
      compression axis orientations are parallel to [1[Formula: see text]0]MoSi2
      (nearly parallel to the growth direction) and [001]MoSi2, respectively.
      [1[Formula: see text]0]MoSi2-oriented DS eutectic composites are strengthened so
      much by forming a script lamellar microstructure and they exhibit yield stress
      values several times higher than those of MoSi2 single crystals of the
      corresponding orientation. The yield stress values increase with the decrease in
      the average thickness of MoSi2 phase in the script lamellar structure, indicating
      that microstructure refinement is effective in obtaining better high-temperature
      strength of these DS eutectic composites. Among the four ternary alloying
      elements tested (V, Nb, Ta and W), Ta is found to be the most effective in
      obtaining higher yield strength at 1400  degrees C.

PMID- 27877899
TI  - Carbon nanotube based transparent conductive films: progress, challenges, and
      perspectives.
AB  - Developments in the manufacturing technology of low-cost, high-quality carbon
      nanotubes (CNTs) are leading to increased industrial applications for this
      remarkable material. One of the most promising applications, CNT based
      transparent conductive films (TCFs), are an alternative technology in future
      electronics to replace traditional TCFs, which use indium tin oxide. Despite
      significant price competition among various TCFs, CNT-based TCFs have good
      potential for use in emerging flexible, stretchable and wearable optoelectronics.
      In this review, we summarize the recent progress in the fabrication, properties,
      stability and applications of CNT-based TCFs. The challenges of current CNT-based
      TCFs for industrial use, in comparison with other TCFs, are considered. We also
      discuss the potential of CNT-based TCFs, and give some possible strategies to
      reduce the production cost and improve their conductivity and transparency.

PMID- 27877901
TI  - Transfer-printing of active layers to achieve high quality interfaces in
      sequentially deposited multilayer inverted polymer solar cells fabricated in air.
AB  - Polymer solar cells (PSCs) are greatly influenced by both the vertical
      concentration gradient in the active layer and the quality of the various
      interfaces. To achieve vertical concentration gradients in inverted PSCs, a
      sequential deposition approach is necessary. However, a direct approach to
      sequential deposition by spin-coating results in partial dissolution of the
      underlying layers which decreases the control over the process and results in not
      well-defined interfaces. Here, we demonstrate that by using a transfer-printing
      process based on polydimethylsiloxane (PDMS) stamps we can obtain increased
      control over the thickness of the various layers while at the same time
      increasing the quality of the interfaces and the overall concentration gradient
      within the active layer of PSCs prepared in air. To optimize the process and
      understand the influence of various interlayers, our approach is based on surface
      free energy, spreading parameters and work of adhesion calculations. The key
      parameter presented here is the insertion of high quality hole transporting and
      electron transporting layers, respectively above and underneath the active layer
      of the inverted structure PSC which not only facilitates the transfer process but
      also induces the adequate vertical concentration gradient in the device to
      facilitate charge extraction. The resulting non-encapsulated devices (active
      layer prepared in air) demonstrate over 40% increase in power conversion
      efficiency with respect to the reference spin-coated inverted PSCs.

PMID- 27877902
TI  - Grafting the surface of carbon nanotubes and carbon black with the chemical
      properties of hyperbranched polyamines.
AB  - Controlling the chemistry on the surface of new carbon materials is a key factor
      to widen the range of their applicability. In this paper we show a grafting
      methodology of polyalkylamines to the surface of carbon nanomaterials, in
      particular, carbon nanotubes and a carbon black. The aim of this work is to reach
      large degrees of covalent functionalization with hyperbranched polyethyleneimines
      (HBPEIs) and to efficiently preserve the strong chelating properties of the
      HBPEIs when they are fixed to the surface of these carbon materials. This
      functionalization opens new possibilities of using these carbon nanotubes-based
      hybrids. The results show that the HBPEIs are covalently attached to the carbon
      materials, forming hybrids. These hybrids emerge from the reaction of amine
      functions of the HBPEIs with carbonyls and carboxylic anhydrides of the carbon
      surface which become imine and imide bonds. Thus, due to the nature of these
      bonds, the pre-oxidized samples with relevant number of C=O groups showed an
      increase in the degree of functionalization with the HBPEIs. Furthermore, both
      the acid-base properties and the coordination capacity for metal ions of the
      hybrids are equivalent to that of the free HBPEIs in solution. This means that
      the chemical characteristics of the HBPEIs have been efficiently transferred to
      the hybrids. To reach this conclusion we have developed a novel procedure to
      assess the acid-base and the coordination properties of the hybrids (solids) by
      means of potentiometric titration. The good agreement of the values obtained for
      the hybrids and for the free HBPEIs in aqueous solution supports the reliability
      of the procedure. Moreover, the high capacity of the hybrids to capture Ni2+ by
      complexation opens new possibilities of using these hybrids to capture high-value
      metal ions such as Pd2+ and Pt2+.

PMID- 27877903
TI  - The novel functional nucleic acid iRed effectively regulates target genes
      following cytoplasmic delivery by faint electric treatment.
AB  - An intelligent shRNA expression device (iRed) contains the minimum essential
      components needed for shRNA production in cells, and could be a novel tool to
      regulate target genes. However, general delivery carriers consisting of cationic
      polymers/lipids could impede function of a newly generated shRNA via
      electrostatic interaction in the cytoplasm. Recently, we found that faint
      electric treatment (fET) of cells enhanced delivery of siRNA and functional
      nucleic acids into the cytoplasm in the absence of delivery carriers. Here, we
      examined fET of cells stably expressing luciferase in the presence of iRed
      encoding anti-luciferase shRNA. Transfection of lipofectamine 2000 (LFN)/iRed
      lipoplexes showed an RNAi effect, but fET-mediated iRed transfection did not,
      likely because of the endosomal localization of iRed after delivery. However, fET
      in the presence of lysosomotropic agent chloroquine significantly improved the
      RNAi effect of iRed/fET to levels that were higher than those for the LFN/iRed
      lipoplexes. Furthermore, the amount of lipid droplets in adipocytes significantly
      decreased following fET with iRed against resistin in the presence of
      chloroquine. Thus, iRed could be a useful tool to regulate target genes following
      fET-mediated cytoplasmic delivery with endosomal escape devices.

PMID- 27877904
TI  - 2D and 3D photonic crystal materials for photocatalysis and electrochemical
      energy storage and conversion.
AB  - This perspective reviews recent advances in inverse opal structures, how they
      have been developed, studied and applied as catalysts, catalyst support
      materials, as electrode materials for batteries, water splitting applications,
      solar-to-fuel conversion and electrochromics, and finally as photonic
      photocatalysts and photoelectrocatalysts. Throughout, we detail some of the
      salient optical characteristics that underpin recent results and form the basis
      for light-matter interactions that span electrochemical energy conversion systems
      as well as photocatalytic systems. Strategies for using 2D as well as 3D
      structures, ordered macroporous materials such as inverse opals are summarized
      and recent work on plasmonic-photonic coupling in metal nanoparticle-infiltrated
      wide band gap inverse opals for enhanced photoelectrochemistry are provided.

PMID- 27877905
TI  - Recent progress in the structure control of Pd-Ru bimetallic nanomaterials.
AB  - Pd and Ru are two key elements of the platinum-group metals that are invaluable
      to areas such as catalysis and energy storage/transfer. To maximize the potential
      of the Pd and Ru elements, significant effort has been devoted to synthesizing Pd
      Ru bimetallic materials. However, most of the reports dealing with this subject
      describe phase-separated structures such as near-surface alloys and physical
      mixtures of monometallic nanoparticles (NPs). Pd-Ru alloys with homogenous
      structure and arbitrary metallic ratio are highly desired for basic scientific
      research and commercial material design. In the past several years, with the
      development of nanoscience, Pd-Ru bimetallic alloys with different architectures
      including heterostructure, core-shell structure and solid-solution alloy were
      successfully synthesized. In particular, we have now reached the stage of being
      able to obtain Pd-Ru solid-solution alloy NPs over the whole composition range.
      These Pd-Ru bimetallic alloys are better catalysts than their parent metal NPs in
      many catalytic reactions, because the electronic structures of Pd and Ru are
      modified by alloying. In this review, we describe the recent development in the
      structure control of Pd-Ru bimetallic nanomaterials. Aiming for a better
      understanding of the synthesis strategies, some fundamental details including
      fabrication methods and formation mechanisms are discussed. We stress that the
      modification of electronic structure, originating from different nanoscale
      geometry and chemical composition, profoundly affects material properties.
      Finally, we discuss open issues in this field.

PMID- 27877906
TI  - Structural behavior of laser-irradiated gamma-Fe2O3 nanocrystals dispersed in
      porous silica matrix : gamma-Fe2O3 to alpha-Fe2O3 phase transition and formation
      of epsilon-Fe2O3.
AB  - The effects of laser irradiation on gamma-Fe2O3 4 +/- 1 nm diameter maghemite
      nanocrystals synthesized by co-precipitation and dispersed into an amorphous
      silica matrix by sol-gel methods have been investigated as function of iron oxide
      mass fraction. The structural properties of gamma-Fe2O3 phase were carefully
      examined by X-ray diffraction and transmission electron microscopy. It has been
      shown that gamma-Fe2O3 nanocrystals are isolated from each other and uniformly
      dispersed in silica matrix. The phase stability of maghemite nanocrystals was
      examined in situ under laser irradiation by Raman spectroscopy and compared with
      that resulting from heat treatment by X-ray diffraction. It was concluded that
      epsilon-Fe2O3 is an intermediate phase between gamma-Fe2O3 and alpha-Fe2O3 and a
      series of distinct Raman vibrational bands were identified with the epsilon-Fe2O3
      phase. The structural transformation of gamma-Fe2O3 into alpha-Fe2O3 occurs
      either directly or via epsilon-Fe2O3, depending on the rate of nanocrystal
      agglomeration, the concentration of iron oxide in the nanocomposite and the
      properties of silica matrix. A phase diagram is established as a function of
      laser power density and concentration.

PMID- 27877907
TI  - Studying the electronic and phononic structure of penta-graphane.
AB  - In this paper, we theoretically consider a two dimensional nanomaterial which is
      a form of hydrogenated penta-graphene; we call it penta-graphane. This structure
      is obtained by adding hydrogen atoms to the sp2 bonded carbon atoms of penta
      graphene. We investigate the thermodynamic and mechanical stability of penta
      graphane. We also study the electronic and phononic structure of penta-graphane.
      Firstly, we use density functional theory with the revised Perdew-Burke-Ernzerhof
      approximation to compute the band structure. Then one-shot GW (G0W0) approach for
      estimating accurate band gap is applied. The indirect band gap of penta-graphane
      is 5.78 eV, which is close to the band gap of diamond. Therefore, this new
      structure is a good electrical insulator. We also investigate the structural
      stability of penta-graphane by computing the phonon structure. Finally, we
      calculate its specific heat capacity from the phonon density of states. Penta
      graphane has a high specific heat capacity, and can potentially be used for
      storing and transferring energy.

PMID- 27877908
TI  - An immuno-wall microdevice exhibits rapid and sensitive detection of IDH1-R132H
      mutation specific to grade II and III gliomas.
AB  - World Health Organization grade II and III gliomas most frequently occur in the
      central nervous system (CNS) in adults. Gliomas are not circumscribed; tumor
      edges are irregular and consist of tumor cells, normal brain tissue, and
      hyperplastic reactive glial cells. Therefore, the tumors are not fully
      resectable, resulting in recurrence, malignant progression, and eventual death.
      Approximately 69-80% of grade II and III gliomas harbor mutations in the
      isocitrate dehydrogenase 1 gene (IDH1), of which 83-90% are found to be the IDH1
      R132H mutation. Detection of the IDH1-R132H mutation should help in the
      differential diagnosis of grade II and III gliomas from other types of CNS tumors
      and help determine the boundary between the tumor and normal brain tissue. In
      this study, we established a highly sensitive antibody-based device, referred to
      as the immuno-wall, to detect the IDH1-R132H mutation in gliomas. The immuno-wall
      causes an immunoreaction in microchannels fabricated using a photo-polymerizing
      polymer. This microdevice enables the analysis of the IDH1 status with a small
      sample within 15 min with substantially high sensitivity. Our results suggested
      that 10% content of the IDH1-R132H mutation in a sample of 0.33 MUl volume, with
      500 ng protein, or from 500 cells is theoretically sufficient for the analysis.
      The immuno-wall device will enable the rapid and highly sensitive detection of
      the IDH1-R132H mutation in routine clinical practice.

PMID- 27877910
TI  - Identifying DNA methylation in a nanochannel.
AB  - DNA methylation is a stable epigenetic modification, which is well known to be
      involved in gene expression regulation. In general, however, analyzing DNA
      methylation requires rather time consuming processes (24-96 h) via DNA
      replication and protein modification. Here we demonstrate a methodology to
      analyze DNA methylation at a single DNA molecule level without any protein
      modifications by measuring the contracted length and relaxation time of DNA
      within a nanochannel. Our methodology is based on the fact that methylation makes
      DNA molecules stiffer, resulting in a longer contracted length and a longer
      relaxation time (a slower contraction rate). The present methodology offers a
      promising way to identify DNA methylation without any protein modification at a
      single DNA molecule level within 2 h.

PMID- 27877909
TI  - Chitosan nanocomposites based on distinct inorganic fillers for biomedical
      applications.
AB  - Chitosan (CHI), a biocompatible and biodegradable polysaccharide with the ability
      to provide a non-protein matrix for tissue growth, is considered to be an ideal
      material in the biomedical field. However, the lack of good mechanical properties
      limits its applications. In order to overcome this drawback, CHI has been
      combined with different polymers and fillers, leading to a variety of chitosan
      based nanocomposites. The extensive research on CHI nanocomposites as well as
      their main biomedical applications are reviewed in this paper. An overview of the
      different fillers and assembly techniques available to produce CHI nanocomposites
      is presented. Finally, the properties of such nanocomposites are discussed with
      particular focus on bone regeneration, drug delivery, wound healing and
      biosensing applications.

PMID- 27877911
TI  - A perspective on the recent progress in solution-processed methods for highly
      efficient perovskite solar cells.
AB  - Perovskite solar cells (PSCs) were developed in 2009 and have led to a number of
      significant improvements in clean energy technology. The power conversion
      efficiency (PCE) of PSCs has increased exponentially and currently stands at 22%.
      PSCs are transforming photovoltaic (PV) technology, outpacing many established PV
      technologies through their versatility and roll-to-roll manufacturing
      compatibility. The viability of low-temperature and solution-processed
      manufacturing has further improved their viability. This article provides a brief
      overview of the stoichiometry of perovskite materials, the engineering behind
      various modes of manufacturing by solution processing methods, and
      recommendations for future research to achieve large-scale manufacturing of high
      efficiency PSCs.

PMID- 27877912
TI  - Photocatalytic activities of coke carbon/g-C3N4 and Bi metal/Bi mixed oxides/g
      C3N4 nanohybrids for the degradation of pollutants in wastewater.
AB  - Different g-C3N4 composite systems (coke carbon/g-C3N4, Bi/Bi2WO6/g-C3N4 and
      Bi/Bi2MoO6/g-C3N4) have been assessed as photocatalysts for wastewater pollutants
      removal. The coke carbon/g-C3N4 hybrid, produced by thermal treatment at 550 
      degrees C of a composite made from melamine cyanurate and coke, only showed
      activity under UV-light irradiation. On the other hand, inorganic Bi spheres/Bi
      mixed oxides/g-C3N4 nanohybrids (Bi/Bi2WO6/g-C3N4 and Bi/Bi2MoO6/g-C3N4
      composites), produced by thermal reduction of Bi2WO6 or Bi2MoO6 by g-C3N4,
      exhibited a remarkable red-shift, up to 620 nm, and allowed the visible-light
      driven degradation of the contaminant, albeit in combination with some
      adsorption.

PMID- 27877913
TI  - Low doses of TiO2-polyethylene glycol nanoparticles stimulate proliferation of
      hepatocyte cells.
AB  - This paper describes the effect of low concentrations of 100 nm polyethylene
      glycol-modified TiO2 nanoparticles (TiO2-PEG NPs) on HepG2 hepatocellular
      carcinoma cells. Proliferation of HepG2 cells increased significantly when the
      cells were exposed to low doses (<100 MUg ml-1) of TiO2-PEG NPs. These results
      were further confirmed by cell counting experiments and cell cycle assays.
      Cellular uptake assays were performed to determine why HepG2 cells proliferate
      with low-dose exposure to TiO2-PEG NPs. The results showed that exposure to lower
      doses of NPs led to less cellular uptake, which in turn decreased cytotoxicity.
      We therefore hypothesized that TiO2-PEG NPs could affect the activity of
      hepatocyte growth factor receptors (HGFRs), which bind to hepatocyte growth
      factor and stimulate cell proliferation. The localization of HGFRs on the surface
      of the cell membrane was detected via immunofluorescence staining and confocal
      microscopy. The results showed that HGFRs aggregate after exposure to TiO2-PEG
      NPs. In conclusion, our results indicate that TiO2-PEG NPs have the potential to
      promote proliferation of HepG2 cells through HGFR aggregation and suggest that
      NPs not only exhibit cytotoxicity but also affect cellular responses.

PMID- 27877914
TI  - Interaction of poly(ethylene glycol)-conjugated phospholipids with supported
      lipid membranes and their influence on protein adsorption.
AB  - We studied real-time interaction between poly(ethylene glycol)-conjugated
      phospholipids (PEG-lipids) and a supported lipid membrane by surface plasmon
      resonance (SPR) spectroscopy to understand dynamic behaviors of PEG-lipids on
      living cell membranes. Supported lipid membranes formed on a hydrophobic surface
      were employed as a model of living cell membrane. We prepared three kinds of PEG
      lipids that carried alkyl chains of different lengths for SPR measurements and
      also performed fluorescence recovery after photobleaching (FRAP) to study the
      influence of acyl chain length on dynamics on the supported membrane. PEG-lipids
      were uniformly anchored to lipid membranes with high fluidity without clustering.
      Incorporation and dissociation rates of PEG-lipids into supported membranes
      strongly depended on the length of acyl chains; longer acyl chains reduced the
      incorporation rate and the dissociation rate of PEG-lipid. Furthermore, protein
      adsorption experiment with bovine serum albumin indicated that PEG modification
      prevented the adsorption of bovine serum albumin on such supported membrane.

PMID- 27877915
TI  - Size control and vacuum-ultraviolet fluorescence of nanosized KMgF3 single
      crystals prepared using femtosecond laser pulses.
AB  - We fabricated nanosized KMgF3 single crystals via a dry pulsed laser ablation
      process using femtosecond laser pulses. The sizes, shapes, and crystallographic
      properties of the crystals were evaluated by transmission electron microscopy
      (TEM). Almost all of the particles were spherical with diameters of less than 100
      nm, and they were not highly agglomerated. Selected-area electron diffraction and
      high-resolution TEM analyses showed that the particles were single crystals.
      Particle diameter was controlled within a wide range by adjusting the Ar ambient
      gas pressure. Under low gas pressures (1 and 10 Pa), relatively small particles
      (primarily 10 nm or less) were observed with a high number density. With
      increasing pressure, the mean diameter increased and the number density
      drastically decreased. Vacuum-ultraviolet cathodoluminescence was observed at 140
      230 nm with blue shift and broadening of spectrum.

PMID- 27877917
TI  - A new start: towards a leading open access journal in materials science.

PMID- 27877918
TI  - Focus on Recent Breakthroughs in Materials Science and Technology.

PMID- 27877916
TI  - Study of local intracellular signals regulating axonal morphogenesis using a
      microfluidic device.
AB  - The establishment and maintenance of axonal patterning is crucial for neuronal
      function. To identify the molecular systems that operate locally to control
      axonal structure, it is important to manipulate molecular functions in restricted
      subcellular areas for a long period of time. Microfluidic devices can be powerful
      tools for such purposes. In this study, we demonstrate the application of a
      microfluidic device to clarify the function of local Ca2+ signals in axons.
      Membrane depolarization significantly induced axonal branch-extension in cultured
      cerebellar granule neurons (CGNs). Local application of nifedipine using a
      polydimethylsiloxane (PDMS)-based microfluidic device demonstrated that Ca2+
      entry from the axonal region via L-type voltage-dependent calcium channels (L
      VDCC) is required for branch extension. Furthermore, we developed a method for
      locally controlling protein levels by combining genetic techniques and use of a
      microfluidic culture system. A vector for enhanced green fluorescent protein
      (EGFP) fused to a destabilizing domain derived from E. coli dihydrofolate
      reductase (ecDHFR) is introduced in neurons by electroporation. By local
      application of the DHFR ligand, trimethoprim (TMP) using a microfluidic device,
      we were able to manipulate differentially the level of fusion protein between
      axons and somatodendrites. The present study revealed the effectiveness of
      microfluidic devices to address fundamental biological issues at subcellular
      levels, and the possibility of their development in combination with molecular
      techniques.

PMID- 27877919
TI  - Software package for structure analysis of quasicrystals.
AB  - Recently a software package for the structure analysis of quasicrystals has been
      released, giving a better environment for determining quasicrystal structures.
      Therefore we can analyze their structures if we know data collection and indexing
      methods and a theory of structure analysis. For the use of the package, the
      structure analysis method and several techniques used in the package are shortly
      reviewed. How to treat key information in the input files of the programs is
      described in detail.

PMID- 27877920
TI  - Precipitate design for creep strengthening of 9% Cr tempered martensitic steel
      for ultra-supercritical power plants.
AB  - It is crucial for the carbon concentration of 9% Cr steel to be reduced to a very
      low level, so as to promote the formation of MX nitrides rich in vanadium as very
      fine and thermally stable particles to enable prolonged periods of exposure at
      elevated temperatures and also to eliminate Cr-rich carbides M23C6. Sub-boundary
      hardening, which is inversely proportional to the width of laths and blocks, is
      shown to be the most important strengthening mechanism for creep and is enhanced
      by the fine dispersion of precipitates along boundaries. The suppression of
      particle coarsening during creep and the maintenance of a homogeneous
      distribution of M23C6 carbides near prior austenite grain boundaries, which
      precipitate during tempering and are less fine, are effective for preventing the
      long-term degradation of creep strength and for improving long-term creep
      strength. This can be achieved by the addition of boron. The steels considered in
      this paper exhibit higher creep strength at 650  degrees C than existing high
      strength steels used for thick section boiler components.

PMID- 27877921
TI  - Active nanocharacterization of nanofunctional materials by scanning tunneling
      microscopy.
AB  - Recent developments in the application of scanning tunneling microscopy (STM) to
      nanofabrication and nanocharacterization are reviewed. The main focus of this
      paper is to outline techniques for depositing and manipulating nanometer-scale
      structures using STM tips. Firstly, the transfer of STM tip material through the
      application of voltage pulses is introduced. The highly reproducible fabrication
      of metallic silver nanodots and nanowires is discussed. The mechanism is thought
      to be spontaneous point-contact formation caused by field-enhanced diffusion to
      the apex of the tip. Transfer through the application of z-direction pulses is
      also introduced. Sub-nanometer displacement pulses along the z-direction form
      point contacts that can be used for reproducible nanodot deposition. Next, the
      discovery of the STM structural manipulation of surface phases is discussed. It
      has been demonstrated that superstructures on Si(001) surfaces can be reverse
      manipulated by controlling the injected carriers. Finally, the fabrication of an
      atomic-scale one-dimensional quantum confinement system by single-atom deposition
      using a controlled point contact is presented. Because of its combined
      nanofabrication and nanocharacterization capabilities, STM is a powerful tool for
      exploring the nanotechnology and nanoscience fields.

PMID- 27877922
TI  - Structural control of Fe-based alloys through diffusional solid/solid phase
      transformations in a high magnetic field.
AB  - A magnetic field has a remarkable influence on solid/solid phase transformations
      and it can be used to control the structure and function of materials during
      phase transformations. The effects of magnetic fields on diffusional solid/solid
      phase transformations, mainly from austenite to ferrite, in Fe-based alloys are
      reviewed. The effects of magnetic fields on the transformation temperature and
      phase diagram are explained thermodynamically, and the transformation behavior
      and transformed structures in magnetic fields are discussed.

PMID- 27877923
TI  - Corrosion resistance of Si-Al-bearing ultrafine-grained weathering steel.
AB  - In the Ultra-steel project at the National Institute for Materials Science
      (NIMS), which run from 1996 to 2005, high-Si-Al-content ultrafine-grained (UFG)
      weathering steel was developed by grain refinement and weathering guidance. It
      was found that this steel has excellent strength, toughness and corrosion
      resistance. Samples were prepared by multi pass warm rolling at temperatures
      between 773 and 873 K. The grain size of steel rolled at 873 K was about 1 MU m,
      and the tensile strength (TS) and elongation (EL) had excellent values of 800 MPa
      and 20%, respectively. In general, steels with high Si and Al contents exhibit
      inferior toughness to carbon steel (SM); however, the toughness of the developed
      sample was markedly improved by grain refinement. Cyclic corrosion tests in the
      presence of chloride ions confirmed that the developed steel exhibited excellent
      corrosion resistance, superior to that of SM. Electron probe microanalysis (EPMA)
      and transmission electron microscopy (TEM) analyses showed that Si and Al mainly
      exist in the inner rust layer. Si and Al were identified as existing in the Si2 +
      and Al3 + states in the nanoscale complex oxides constituting the inner rust
      layer. Electrochemical impedance spectroscopy(EIS) measurement showed that the
      corrosion reaction resistance (Rt) of the developed steel was much greater than
      that of SM. In the developed steel, the nanoscale complex oxides were formed in
      the inner rust layer, which increased Rt, and resulted in the excellent corrosion
      resistance.

PMID- 27877924
TI  - Phase-field modeling of microstructure evolutions in magnetic materials.
AB  - Recently, the phase-field method has been extended and utilized across many
      fields of materials science. Since this method can incorporate, systematically,
      the effect of the coherency induced by lattice mismatch and the applied stress as
      well as the external electrical and magnetic fields, it has been applied to many
      material processes including solidification, solid-state phase transformations
      and various types of complex microstructure changes. In this paper, we focus on
      the recent phase-field simulations of real magnetic materials, and the simulation
      method for magnetic materials is explained comprehensively. Several applications
      of the phase-field method to clarifying the microstructure changes in magnetic
      materials, such as Ni2MnGa ferromagnetic shape memory alloy, FePt nanogranular
      thin film, Co-Sm-Cu rare-earth magnet, Fe-Cr-Co spinodal magnet, and Fe-C steel
      with external magnetic field, are demonstrated. Furthermore, the general concept
      of the effective strategy for controlling microstructure in magnetic materials is
      proposed.

PMID- 27877925
TI  - Advances in principal factors influencing carbon dioxide adsorption on zeolites.
AB  - We report the advances in the principal structural and experimental factors that
      might influence the carbon dioxide (CO2) adsorption on natural and synthetic
      zeolites. The CO2 adsorption is principally govern by the inclusion of
      exchangeable cations (countercations) within the cavities of zeolites, which
      induce basicity and an electric field, two key parameters for CO2 adsorption.
      More specifically, these two parameters vary with diverse factors including the
      nature, distribution and number of exchangeable cations. The structure of
      framework also determines CO2 adsorption on zeolites by influencing the basicity
      and electric field in their cavities. In fact, the basicity and electric field
      usually vary inversely with the Si/Al ratio. Furthermore, the CO2 adsorption
      might be limited by the size of pores within zeolites and by the carbonates
      formation during the CO2 chemisorption. The polarity of molecules adsorbed on
      zeolites represents a very important factor that influences their interaction
      with the electric field. The adsorbates that have the most great quadrupole
      moment such as the CO2, might interact strongly with the electric field of
      zeolites and this favors their adsorption. The pressure, temperature and presence
      of water seem to be the most important experimental conditions that influence the
      adsorption of CO2. The CO2 adsorption increases with the gas phase pressure and
      decreases with the rise of temperature. The presence of water significantly
      decreases adsorption capacity of cationic zeolites by decreasing strength and
      heterogeneity of the electric field and by favoring the formation of
      bicarbonates. The optimization of the zeolites structural characteristics and the
      experimental conditions might enhance substantially their CO2 adsorption capacity
      and thereby might give rise to the excellent adsorbents that may be used to
      capturing the industrial emissions of CO2.

PMID- 27877926
TI  - Icosahedral clusters, icosaheral order and stability of quasicrystals-a view of
      metallurgy.
AB  - We review the stability of various icosahedral quasicrystals (iQc) from a
      metallurgical viewpoint. The stability of stable iQcs is well interpreted in
      terms of Hume-Rothery rules, i.e. atomic size factor and valence electron
      concentration, e/a. For metastable iQcs, we discuss the role of phason disorder
      introduced by rapid solidification, in structural stability and its interplay
      with chemical order and composition.

PMID- 27877927
TI  - Highly spin-polarized materials and devices for spintronics*.
AB  - The performance of spintronics depends on the spin polarization of the current.
      In this study half-metallic Co-based full-Heusler alloys and a spin filtering
      device (SFD) using a ferromagnetic barrier have been investigated as highly spin
      polarized current sources. The multilayers were prepared by magnetron sputtering
      in an ultrahigh vacuum and microfabricated using photolithography and Ar ion
      etching. We investigated two systems of Co-based full-Heusler alloys, Co2Cr1 - x
      Fe x Al (CCFA(x)) and Co2FeSi1 - x Al x (CFSA(x)) and revealed the structure and
      magnetic and transport properties. We demonstrated giant tunnel magnetoresistance
      (TMR) of up to 220% at room temperature and 390% at 5 K for the magnetic tunnel
      junctions (MTJs) using Co2FeSi0.5Al0.5 (CFSA(0.5)) Heusler alloy electrodes. The
      390% TMR corresponds to 0.81 spin polarization for CFSA(0.5) at 5 K. We also
      investigated the crystalline structure and local structure around Co atoms by x
      ray diffraction (XRD) and nuclear magnetic resonance (NMR) analyses,
      respectively, for CFSA films sputtered on a Cr-buffered MgO (001) substrate
      followed by post-annealing at various temperatures in an ultrahigh vacuum. The
      disordered structures in CFSA films were clarified by NMR measurements and the
      relationship between TMR and the disordered structure was discussed. We clarified
      that the TMR of the MTJs with CFSA(0.5) electrodes depends on the structure, and
      is significantly higher for L21 than B2 in the crystalline structure. The second
      part of this paper is devoted to a SFD using a ferromagnetic barrier. The Co
      ferrite is investigated as a ferromagnetic barrier because of its high Curie
      temperature and high resistivity. We demonstrate the strong spin filtering effect
      through an ultrathin insulating ferrimagnetic Co-ferrite barrier at a low
      temperature. The barrier was prepared by the surface plasma oxidization of a
      CoFe2 film deposited on a MgO (001) single crystal substrate, wherein the spinel
      structure of CoFe2O4 (CFO) and an epitaxial relationship of MgO(001)[100]/CoFe2
      (001)]110]/CFO(001)[100] were induced. A SFD consisting of CoFe2 /CFO/Ta on a MgO
      (001) substrate exhibits the inverse TMR of - 124% at 10 K when the configuration
      of the magnetizations of CFO and CoFe2 changes from parallel to antiparallel. The
      inverse TMR suggests the negative spin polarization of CFO, which is consistent
      with the band structure of CFO obtained by first principle calculation. The -
      124% TMR corresponds to the spin filtering efficiency of 77% by the CFO barrier.

PMID- 27877928
TI  - Rational design of new materials for spintronics: Co2FeZ (Z=Al, Ga, Si, Ge).
AB  - Spintronic is a multidisciplinary field and a new research area. New materials
      must be found for satisfying the different types of demands. The search for
      stable half-metallic ferromagnets and ferromagnetic semiconductors with Curie
      temperatures higher than room temperature is still a challenge for solid state
      scientists. A general understanding of how structures are related to properties
      is a necessary prerequisite for material design. Computational simulations are an
      important tool for a rational design of new materials. The new developments in
      this new field are reported from the point of view of material scientists. The
      development of magnetic Heusler compounds specifically designed as material for
      spintronic applications has made tremendous progress in the very recent past.
      Heusler compounds can be made as half-metals, showing a high spin polarization of
      the conduction electrons of up to 100% in magnetic tunnel junctions. High Curie
      temperatures were found in Co2-based Heusler compounds with values up to 1120 K
      in Co2FeSi. The latest results at the time of writing are a tunnelling magnet
      resistance (TMR) device made from the Co2FeAl0.5Si0.5 Heusler compound and
      working at room temperature with a (TMR) effect higher than 200%. Good interfaces
      and a well-ordered compound are the precondition to realize the predicted half
      metallic properties. The series Co2FeAl1- x Si x is found to exhibit half
      metallic ferromagnetism over a broad range, and it is shown that electron doping
      stabilizes the gap in the minority states for x=0.5. This might be a reason for
      the exceptional temperature behaviour of Co2FeAl0.5Si0.5 TMR devices. Using x-ray
      diffraction (XRD), it was shown conclusively that Co2FeAl crystallizes in the B2
      structure whereas Co2FeSi crystallizes in the L21 structure. For the compounds
      Co2FeGa or Co2FeGe, with Curie temperatures expected higher than 1000 K, the
      standard XRD technique using laboratory sources cannot be used to easily
      distinguish between the two structures. For this reason, the EXAFS technique was
      used to elucidate the structure of these two compounds. Analysis of the data
      indicated that both compounds crystallize in the L21 structure which makes these
      two compounds suitable new candidates as materials in magnetic tunnel junctions.

PMID- 27877930
TI  - Electrochromic materials using mechanically interlocked molecules.
AB  - Recent investigations on the design and synthesis of electrochromic materials
      based on switchable three-station [2]catenanes are summarized. The reasoning and
      preliminary experiments behind the design of electrochemically controllable red
      green-blue (RGB), donor-acceptor [2]catenanes are presented. A basis for color
      generation is discussed in which the tetracationic cyclophane, cyclobis(paraquat
      p-phenylene), serves as the pi-electron deficient ring which circumrotates
      between three pi-electron rich recognition sites within a macrocyclic polyether,
      generating the three different colors (RGB) based on the different charge
      transfer interactions between the tetracationic cyclophane and recognition sites
      based on 1,5-dioxynaphthalene (R), tetrathiafulvalene (G) and benzidine (B).
      Issues relating to the realization of an RGB [2]catenane are raised and
      discussed: they include (i) color tuning, (ii) thermodynamic considerations,
      (iii) electrochemistry on model compounds, (iv) molecular design, (v) the
      electrochemical behavior of three-station [2]catenanes and (vi) electrochromism
      in polymer gel matrices. Finally, the challenges that need to be met in the
      future if the ideal RGB catenane is to be prepared, are outlined.

PMID- 27877929
TI  - Metallo-supramolecular modules as a paradigm for materials science.
AB  - Metal ion coordination in discrete or extended metallo-supramolecular assemblies
      offers ample opportunity to fabricate and study devices and materials that are
      equally important for fundamental research and new technologies. Metal ions
      embedded in a specific ligand field offer diverse thermodynamic, kinetic,
      chemical, physical and structural properties that make these systems promising
      candidates for active components in functional materials. A key challenge is to
      improve and develop methodologies for placing these active modules in suitable
      device architectures, such as thin films or mesophases. This review highlights
      recent developments in extended, polymeric metallo-supramolecular systems and
      discrete polyoxometalates with an emphasis on materials science.

PMID- 27877932
TI  - Tunneling magnetoresistance from a symmetry filtering effect.
AB  - This paper provides a brief overview of the young, but rapidly growing field of
      spintronics. Its primary objective is to explain how as electrons tunnel through
      simple insulators such as MgO, wavefunctions of certain symmetries are
      preferentially transmitted. This symmetry filtering property can be converted
      into a spin-filtering property if the insulator is joined epitaxially to a
      ferromagnetic electrode with the same two-dimensional symmetry parallel to the
      interface. A second requirement of the ferromagnetic electrodes is that a
      wavefunction with the preferred symmetry exists in one of the two spin channels
      but not in the other. These requirements are satisfied for electrons traveling
      perpendicular to the interface for Fe-MgO-Fe tunnel barriers. This leads to a
      large change in the resistance when the magnetic moment of one of the electrodes
      is rotated relative to those of the other electrode. This large tunneling
      magnetoresistance effect is being used as the read sensor in hard drives and may
      form the basis for a new type of magnetic memory.

PMID- 27877931
TI  - Spin current, spin accumulation and spin Hall effect.
AB  - Nonlocal spin transport in nanostructured devices with ferromagnetic injector
      (F1) and detector (F2) electrodes connected to a normal conductor (N) is studied.
      We reveal how the spin transport depends on interface resistance, electrode
      resistance, spin polarization and spin diffusion length, and obtain the
      conditions for efficient spin injection, spin accumulation and spin current in
      the device. It is demonstrated that the spin Hall effect is caused by spin-orbit
      scattering in nonmagnetic conductors and gives rise to the conversion between
      spin and charge currents in a nonlocal device. A method of evaluating spin-orbit
      coupling in nonmagnetic metals is proposed.

PMID- 27877933
TI  - Optics of high-performance electron microscopes.
AB  - During recent years, the theory of charged particle optics together with advances
      in fabrication tolerances and experimental techniques has lead to very
      significant advances in high-performance electron microscopes. Here, we will
      describe which theoretical tools, inventions and designs have driven this
      development. We cover the basic theory of higher-order electron optics and of
      image formation in electron microscopes. This leads to a description of different
      methods to correct aberrations by multipole fields and to a discussion of the
      most advanced design that take advantage of these techniques. The theory of
      electron mirrors is developed and it is shown how this can be used to correct
      aberrations and to design energy filters. Finally, different types of energy
      filters are described.

PMID- 27877934
TI  - Chemistry and application of flexible porous coordination polymers.
AB  - Porous coordination polymers (PCPs), which are microporous materials, have been
      given much attention from both scientific and commercial aspects regarding their
      application to gas storage, gas separation and catalytic reaction because of the
      regularity of their pore shape and pore size, accompanied with the functionality.
      Moreover, in recent years, flexible PCPs, which are structurally transformable
      depending upon external stimuli, have been attractive because they provide unique
      properties, dissimilar to those of zeolites. In this review, the chemistry and
      application of flexible crystalline PCPs are summarized and discussed.

PMID- 27877936
TI  - Nanofabrication by advanced electron microscopy using intense and focused beam*.
AB  - The nanogrowth and nanofabrication of solid substances using an intense and
      focused electron beam are reviewed in terms of the application of scanning and
      transmission electron microscopy (SEM, TEM and STEM) to control the size,
      position and structure of nanomaterials. The first example discussed is the
      growth of freestanding nanotrees on insulator substrates by TEM. The growth
      process of the nanotrees was observed in situ and analyzed by high-resolution TEM
      (HRTEM) and was mainly controlled by the intensity of the electron beam. The
      second example is position- and size-controlled nanofabrication by STEM using a
      focused electron beam. The diameters of the nanostructures grown ranged from 4 to
      20 nm depending on the size of the electron beam. Magnetic nanostructures were
      also obtained using an iron-containing precursor gas, Fe(CO)5. The freestanding
      iron nanoantennas were examined by electron holography. The magnetic field was
      observed to leak from the nanostructure body which appeared to act as a
      'nanomagnet'. The third example described is the effect of a vacuum on the size
      and growth process of fabricated nanodots containing W in an ultrahigh-vacuum
      field-emission TEM (UHV-FE-TEM). The size of the dots can be controlled by
      changing the dose of electrons and the partial pressure of the precursor. The
      smallest particle size obtained was about 1.5 nm in diameter, which is the
      smallest size reported using this method. Finally, the importance of a smaller
      probe and a higher electron-beam current with atomic resolution is emphasized and
      an attempt to develop an ultrahigh-vacuum spherical aberration corrected STEM (Cs
      corrected STEM) at NIMS is reported.

PMID- 27877937
TI  - Present status and future prospects of spherical aberration corrected TEM/STEM
      for study of nanomaterials*.
AB  - The present status of Cs-corrected TEM/STEM is described from the viewpoint of
      the observation of nanomaterials. Characteristic features in TEM and STEM are
      explained using the experimental data obtained by our group and other research
      groups. Cs correction up to the 3rd-order aberration of an objective lens has
      already been established and research interest is focused on correcting the 5th
      order spherical aberration and the chromatic aberration in combination with the
      development of a monochromator below an electron gun for smaller point-to-point
      resolution in optics. Another fundamental area of interest is the limitation of
      TEM and STEM resolution from the viewpoint of the scattering of electrons in
      crystals. The minimum size of the exit-wave function below samples undergoing TEM
      imaging is determined from the calculation of scattering around related atomic
      columns in the crystals. STEM does not have this limitation because the
      resolution is, in principle, determined by the probe size. One of the future
      prospects of Cs-corrected TEM/STEM is the possibility of extending the space
      around the sample holder by correcting the chromatic and spherical aberrations.
      This wider space will contribute to the ease of performing in situ experiments
      and various combinations of TEM and other analysis methods. High-resolution, in
      situ dynamic and 3D observations/analysis are the most important keywords in the
      next decade of high-resolution electron microscopy.

PMID- 27877938
TI  - Investigation of ordering phenomenon in Me-Pt (Me=Fe,Ni) liquid alloys.
AB  - The phase diagrams of Fe-Pt and Ni-Pt liquid alloy systems show the existence of
      FePt and NiPt intermetallic compounds, respectively, in their solid intermediate
      states, and the associative tendency between unlike atoms in these liquid alloys
      has been analysed using the self-association model. The concentration dependences
      of mixing properties such as the free energy of mixing, GM; the concentration
      fluctuations, Scc(0), in the long-wavelength limits; the chemical short-range
      order (CSRO) parameter, alpha1; as well as the chemical diffusion, enthalpy and
      entropy of the mixing of Fe-Pt and Ni-Pt liquid alloys have been investigated to
      determine the nature of ordering in the liquid alloys. The results show that
      heterocoordination occurs in the alloys at all concentrations. The effect of CSRO
      on Scc(0), chemical diffusion, D, and the order parameter, alpha1, has been
      considered. The ordering phenomenon in the liquid alloys is also related to the
      effect of the atomic size mismatch volume on Scc(0).

PMID- 27877939
TI  - A novel method for synthesis of alpha-Si3N4 nanowires by sol-gel route.
AB  - Silicon nitride (Si3 N4) nanowires have been prepared by carbothermal reduction
      followed by the nitridation (CTRN) of silica gel containing ultrafine excess
      carbon obtained by the decomposition of dextrose over the temperature range of
      1200-1350  degrees C. This innovative process involves repeated evacuation
      followed by purging of nitrogen gas so that the interconnected nanopores of the
      gel are filled with nitrogen gas prior to heat treatment. During heat treatment
      at higher temperatures, the presence of nitrogen gas in the nanopores of the gel
      starts the CTRN reaction simultaneously throughout the bulk of the gel, leading
      to the formation of Si3 N4 nanowires. The in situ generated ultrafine carbon
      obtained by the decomposition of dextrose decreases the partial pressure of
      oxygen in the system to stabilize the nanowires. The nanowires synthesized by
      this process are of ~500 nm diameter and ~0.2 mm length. The product was
      characterized by scanning electron microscope (SEM), energy dispersive x-ray
      analysis (EDX), x-ray diffraction (XRD) and infrared (IR) spectra.

PMID- 27877940
TI  - Modeling the dependence of strength on grain sizes in nanocrystalline materials.
AB  - A model was developed to describe the grain size dependence of hardness (or
      strength) in nanocrystalline materials by combining the Hall-Petch relationship
      for larger grains with a coherent polycrystal model for nanoscale grains and
      introducing a log-normal distribution of grain sizes. The transition from the
      Hall-Petch relationship to the coherent polycrystal mechanism was shown to be a
      gradual process. The hardness in the nanoscale regime was observed to increase
      with decreasing grain boundary affected zone (or effective grain boundary
      thickness, Delta) in the form of Delta-1/2. The critical grain size increased
      linearly with increasing Delta. The variation of the calculated hardness value
      with the grain size was observed to be in agreement with the experimental data
      reported in the literature.

PMID- 27877941
TI  - Microstructural development in Al/MgAl2O4in situ metal matrix composite using
      value-added silica sources.
AB  - Al/MgAl2O4in situ metal matrix composites have been synthesized using value-added
      silica sources (microsilica and rice husk ash) containing ~97% SiO2 in Al-5 wt.%
      Mg alloy. The thermodynamics and kinetics of MgAl2O4 formation are discussed in
      detail. The MgO and MgAl2O4 phases were found to dominate in microsilica (MS) and
      rice husk ash (RHA) value-added composites, respectively, during the initial
      stage of holding the composites at 750  degrees C. A transition phase between MgO
      and MgAl2O4 was detected by the scanning electron microscopy and energy
      dispersive spectroscopy (SEM-EDS) analysis of the particles extracted from the
      composite using 25% NaOH solution. This confirms that MgO is gradually
      transformed to MgAl2O4 by the reaction 3SiO2(s)+2MgO(s)+4Al(l)
      >2MgAl2O4(s)+3Si(l). The stoichiometry of MgAl2O4, n, computed by a new
      methodology is between 0.79 and 1.18. The reaction between the silica sources and
      the molten metal stopped after 55% of the silica source was consumed. A gradual
      increase in mean MgAl2O4 crystallite size, D, from 24 to 36 nm was observed in
      the samples held for 10 h.

PMID- 27877942
TI  - Preparation of PV dF-based electrospun membranes and their application as
      separators.
AB  - A one-step method preparing of poly(vinylidene fluoride)-based electrospun
      membranes (PEMs) containing TiO2 has been developed. The effect of TiO2 on the
      morphology, degree of crystallization and electrochemical behavior of PEMs was
      investigated by scanning electron microscopy (SEM), atomic force microscopy
      (AFM), differential scanning calorimetry (DSC) and electrochemical measurements.
      The PEMs containing TiO2 show improved ionic conductivity and cycling performance
      compared with pure PEMs.

PMID- 27877943
TI  - Surface characteristics and antibacterial activity of a silver-doped carbon
      monolith.
AB  - A carbon monolith with a silver coating was prepared and its antimicrobial
      behaviour in a flow system was examined. The functional groups on the surface of
      the carbon monolith were determined by temperature-programmed desorption and
      Boehm's method, and the point of zero charge was determined by mass titration.
      The specific surface area was examined by N2 adsorption using the Brunauer,
      Emmett and Teller (BET) method. As a test for the surface activity, the
      deposition of silver from an aqueous solution of a silver salt was used. The
      morphology and structure of the silver coatings were characterized by scanning
      electron microscopy and x-ray diffraction. The resistance to the attrition of the
      silver deposited on the carbon monolith was tested. The antimicrobial activity of
      the carbon monolith with a silver coating was determined using standard
      microbiological methods. Carbon monolith samples with a silver coating showed
      good antimicrobial activity against Escherichia coli, Staphylococcus aureus and
      Candida albicans, and are therefore suitable for water purification, particularly
      as personal disposable water filters with a limited capacity.

PMID- 27877944
TI  - Quartz crystal microbalance and spectroscopy measurements for acid doping in
      polyaniline films.
AB  - We investigated the doping of thin polyaniline (PANI) films, prepared by the
      chemical oxidation of aniline, with different acids. The initial step in the
      investigation is the preparation of PANI films from aqueous hydrochloric acid
      solution. This is followed by dedoping with ammonia to obtain a PANI base, which
      is subsequently doped with strong acids (e.g. hydrochloric, sulfuric, phosphoric
      and trichloroacetic acids) and with a weak acid (acetic acid). The dopant weight
      fraction ( w ), which is connected with the gain of mass during the doping of
      PANI, was determined in situ using a quartz crystal microbalance (QCM). The
      behavior of PANI upon doping with different anions derived from strong acids
      indicates that both proton and the anion uptake into the polymer chains occur
      sharply, rapidly, completely, and reversibly. However the uptake in the case in
      acetic acid is characterized by slow diffusion. The doping was studied at
      different concentrations of acetic acid. A second cycle of dedoping-redoping was
      also performed. The kinetics of the doping reaction is dominated by Fickian
      diffusion kinetics. The diffusion coefficients (D) of the dopant ions into the
      PANI chains were determined using the QCM and by UV-Vis absorption spectroscopy
      in the range of (0.076-1.64)* 10-15 cm2 s-1. It was found that D in the second
      cycle of doping is larger than that evaluated from the first cycle of doping for
      high concentrations of acetic acid. D for the diffusion and for the dopant ion
      expulsion from the PANI chains was also determined during the redoping process.
      It was found that D for acetic acid ions in the doping process is larger than
      that calculated for the dedoping process.

PMID- 27877945
TI  - Parallel glide: flow of dislocations with internal stress source/sink
      distribution.
AB  - The unexpected glide of dislocations on a plane parallel to the film/substrate
      interface in ultrathin copper films, which has been called parallel glide (Balk
      et al 2003 Acta Metall. 51 447), is described using an analytical model. The
      phenomenon is observed as a problem involving inlet/outlet flow from different
      positions of a grain boundary into the grain channel. In this sense, parallel
      glide is presented as the flow of dislocations with an internal stress
      source/sink distribution.

PMID- 27877946
TI  - Shape recovery and irrecoverable strain control in polyurethane shape-memory
      polymer.
AB  - In shape-memory polymers, large strain can be fixed at a low temperature and
      thereafter recovered at a high temperature. If the shape-memory polymer is held
      at a high temperature for a long time, the irrecoverable strain can attain a new
      intermediate shape between the shape under the maximum stress and the primary
      shape. Irrecoverable strain control can be applied to the fabrication of a shape
      memory polymer element with a complex shape in a simple method. In the present
      study, the influence of the strain-holding conditions on the shape recovery and
      the irrecoverable strain control in polyurethane shape-memory polymer is
      investigated by tension test of a film and three-point bending test of a sheet.
      The higher the shape-holding temperature and the longer the shape-holding time,
      the higher the irrecoverable strain rate. The equation that expresses the
      characteristics of the irrecoverable strain control is formulated.

PMID- 27877947
TI  - Focus on Magneto-Science.

PMID- 27877948
TI  - Focus on the Degradation and Stability of Polymers.

PMID- 27877949
TI  - Progress in cold roll bonding of metals.
AB  - Layered composite materials have become an increasingly interesting topic in
      industrial development. Cold roll bonding (CRB), as a solid phase method of
      bonding same or different metals by rolling at room temperature, has been widely
      used in manufacturing large layered composite sheets and foils. In this paper, we
      provide a brief overview of a technology using layered composite materials
      produced by CRB and discuss the suitability of this technology in the fabrication
      of layered composite materials. The effects of process parameters on bonding,
      mainly including process and surface preparation conditions, have been analyzed.
      Bonding between two sheets can be realized when deformation reduction reaches a
      threshold value. However, it is essential to remove surface contamination layers
      to produce a satisfactory bond in CRB. It has been suggested that the degreasing
      and then scratch brushing of surfaces create a strong bonding between the layers.
      Bonding mechanisms, in which the film theory is expressed as the major mechanism
      in CRB, as well as bonding theoretical models, have also been reviewed. It has
      also been showed that it is easy for bcc structure metals to bond compared with
      fcc and hcp structure metals. In addition, hardness on bonding same metals plays
      an important part in CRB. Applications of composites produced by CRB in
      industrial fields are briefly reviewed and possible developments of CRB in the
      future are also described.

PMID- 27877950
TI  - Fabrication and characterization of nanostructures on insulator substrates by
      electron-beam-induced deposition.
AB  - The fabrication, characterization, and decoration with metallic nanoparticles of
      nanostructures such as nanowhiskers, nanodendrites, and fractal-like nanotrees on
      insulator substrates by electron-beam-induced deposition (EBID) are reviewed.
      Nanostructures with different morphologies of whiskers, dendrites, or trees are
      fabricated on insulator (Al2O3 or SiO2) substrates by EBID in transmission
      electron microscopes by controlling the irradiation conditions such as the
      electron beam intensity. The growth of the nanostructure is related to the
      accumulation of charges on the surface of a substrate during electron-beam
      irradiation. A high concentration of the target metallic element and nanocrystal
      grains of the element are contained in the fabricated nanostructures. The process
      of growth of the nanostructures is explained qualitatively on the basis of
      mechanisms in which the formation of the nanostructures is considered to be
      related to the nanoscaled unevenness of the charge distribution on the surface of
      the substrate, the movement of the charges to the convex surface of the
      substrate, and the accumulation of charges at the tip of the grown nanostructure.
      Novel composite structures of Pt nanoparticle/tungsten (W) nanodendrite or Au
      nanoparticle/W nanodendrite are fabricated by the decoration of W nanodendrites
      with metallic elements. Because they have superior features, such as a large
      specific surface area, a freestanding structure on substrates, a typical size of
      several nanometers of the tip or the branch, and high purity, the nanostructures
      may have applications in technologies such as catalysts, sensors, and electron
      emitters. However, there are still some subjects that should be further studied
      before their application.

PMID- 27877951
TI  - On the glass forming ability of liquid alloys.
AB  - By using the concepts of the short-range order (SRO) and middle-range order (MRO)
      characterizing structures, an attempt has been made to describe the glass forming
      ability (GFA) of liquid alloys. This includes the effect of more than two kinds
      of SRO in the liquid caused by the addition of second and third elements to a
      metallic solvent. The minimum solute concentration is related to the atomic
      volume mismatch estimated from the cube of the atomic radius. The optimum solute
      concentration for good glass formability in several binary and some ternary
      alloys is discussed on the basis of the empirical guideline. A new approach to
      obtaining good GFA of liquid alloys is based on four main factors: (i) formation
      of new SRO and coexistence of two or more kinds of SRO, (ii) stabilization of
      dense random packing structure by restraining the atomic redistribution for
      initiating the nucleation and growth process, (iii) formation of a stable cluster
      (SC) or the MRO by the harmonious coupling of SROs, and (iv) difference between
      SRO characterizing the liquid structure and the near-neighbor environment in the
      corresponding equilibrium crystalline phases. The use of interaction parameters,
      widely used in the thermodynamics of multicomponent metallic solutions, is
      proposed for effectively selecting the third solute element (X3) for enhancing
      the GFA of a metallic liquid (M) containing the second solute (X2). Fe70-B20
      (X3)10 alloys (X3=Cr, W, Nb, Zr and Hf) are used for illustration. Two typical
      model structures denoted by the Bernal and chemical-order types are used in
      describing the new glass structure as a function of solute concentration.

PMID- 27877952
TI  - 3D physical modeling of anisotropic grain growth at high temperature in local
      strong magnetic force field.
AB  - A new mechanism based on the effect of local magnetic forces on diffusing ions
      around a growing ferromagnetic precipitate is proposed. A 3D simulation based
      only on physical parameters is undertaken in which main assumption is of
      interface limited growth controlled by the effect of both curvature and local
      magnetic field distortion. Although usually neglected in magnetic field effect
      mechanisms, it is shown that these local magnetic forces acting on a single
      paramagnetic ion can change markedly affect the growth process and induce strong
      shape anisotropy.

PMID- 27877953
TI  - Effects of a high-gradient magnetic field on the migratory behavior of primary
      crystal silicon in hypereutectic Al-Si alloy.
AB  - The migration of primary Si grains during the solidification of Al-18 wt%Si alloy
      under a high-gradient magnetic field has been investigated experimentally. It was
      found that under a gradient magnetic field, the primary Si grains migrated toward
      one end of the specimen, forming a Si-rich layer, and the thickness of the Si
      rich layer increased with increasing magnetic flux density. No movement of Si
      grains was apparent under a magnetic field below 2.3 T. For magnetic fields above
      6.6 T, however, the thickness of the Si-rich layer was almost constant. It was
      shown that the static field also played a role in impeding the movement of the
      grains. The primary Si grains were refined in the Si layer, even though the
      primary silicon grains were very dense. The effect of the magnetic flux density
      on the migratory behavior is discussed.

PMID- 27877954
TI  - Control of nonmagnetic particles using a magnetic field.
AB  - A force and/or torque are induced in a material under the imposition of a
      magnetic field. Their magnitudes are different from those acting on the
      surrounding materials because of the difference in their physical properties.
      Therefore, a magnetic field is a powerful tool for controlling a second phase in
      a mother phase such as particles suspended in a liquid. In this paper, we focus
      on two processes. The first one is a novel method of magnetic filtration in which
      schwertmannite particles in wastewater are controlled using a magnetic field. The
      second one is a refining process for a metallic alloy structure during
      solidification in which solid particles suspended in the liquid phase are
      controlled using the force excited by the simultaneous imposition of a magnetic
      field and alternating current.

PMID- 27877935
TI  - Challenges and breakthroughs in recent research on self-assembly.
AB  - The controlled fabrication of nanometer-scale objects is without doubt one of the
      central issues in current science and technology. However, existing fabrication
      techniques suffer from several disadvantages including size-restrictions and a
      general paucity of applicable materials. Because of this, the development of
      alternative approaches based on supramolecular self-assembly processes is
      anticipated as a breakthrough methodology. This review article aims to
      comprehensively summarize the salient aspects of self-assembly through the
      introduction of the recent challenges and breakthroughs in three categories: (i)
      types of self-assembly in bulk media; (ii) types of components for self-assembly
      in bulk media; and (iii) self-assembly at interfaces.

PMID- 27877955
TI  - Magnetic and structural phase transitions of MnBi under high magnetic fields.
AB  - High-field x-ray diffraction and magnetization measurements and differential
      thermal analysis (DTA) were carried out for polycrystalline MnBi with an NiAs
      type hexagonal structure to investigate its magnetic and structural phase
      transitions. The lattice parameter a rapidly decreases below the spin
      reorientation temperature TSR(=90 K) in a zero magnetic field. The parameter c
      decreases gradually with decreasing temperature and exhibits an anomaly in the
      vicinity of TSR. By applying a magnetic field of 5 T, the parameter a increases
      by ~0.05% when T<TSR and varies smoothly when 8<=T<=300 K. DTA data show that the
      magnetic phase transition temperature from the ferromagnetic state to the
      paramagnetic state increases linearly at a rate of 2 KT-1 with increasing
      magnetic field up to 14 T.

PMID- 27877956
TI  - Laser flash photolysis and magnetic-field-effect studies on interaction of
      thymine and thymidine with menadione: role of sugar in controlling reaction
      pattern.
AB  - The magnetic field effect (MFE) in conjunction with laser flash photolysis has
      been used for the study of the interaction of one of the small drug like quinone
      molecules, 2-methyl, 1,4-naphthoquinone, commonly known as menadione (MQ), with
      one of the DNA bases, thymine (THN), and its corresponding nucleoside, thymidine
      (THDN), in acetonitrile (ACN) and sodium dodecylsulfate (SDS) micelles. It has
      been observed that THN undergoes electron transfer (ET) and hydrogen (H)
      abstraction with MQ, while THDN undergoes only H abstraction in both the media.
      However, our earlier studies showed that a purine base, adenine (ADN), and its
      nucleoside, 2'-deoxyadenosine (ADS), undergo ET in ACN and H abstraction in SDS.
      Here we have attempted to explain the differences in the reactions of these DNA
      bases with MQ. We also reveal the crucial role of a sugar unit in altering the
      behavior of purine and pyrimidine bases with respect to ET and H abstraction.

PMID- 27877958
TI  - Microwave magnetoresistance in Ge:Mn nanowires and nanofilms.
AB  - The Lorentzian and spin-scattering components of magnetoresistance were found and
      distinguished in Ge:Mn thin films. The suppression of microwave magnetoresistance
      by the limitation of the dimensionality of Ge nanowires doped with Mn has been
      revealed. Spin-wave resonance in the long-ordered magnetic state and
      ferromagnetic resonance in GeMn clusters have been detected.

PMID- 27877957
TI  - Magnetoconductivity and magnetoluminescence studies in bipolar and almost hole
      only sandwich devices made from films of a pi-conjugated molecule.
AB  - We present magnetoconductivity and magnetoluminescence measurements in sandwich
      devices made from films of a pi-conjugated molecule and demonstrate effects of
      more than 30 and 50% magnitude, respectively, in fields of 100 mT at room
      temperature. It has previously been recognized that the effect is caused by
      hyperfine coupling, and that it is phenomenologically similar to other magnetic
      field effects that act on electron-hole pairs, which are well-known in spin
      chemistry. However, we show that the very large magnitude of the effect
      contradicts present knowledge of the electron-hole pair recombination processes
      in electroluminescent pi-conjugated molecules, and that the effect persists even
      in almost hole-only devices. Therefore, this effect is likely caused by the
      interaction of radical pairs of equal charge.

PMID- 27877959
TI  - Magnetic field effects on electrochemical metal depositions.
AB  - This paper discusses recent experimental and numerical results from the authors'
      labs on the effects of moderate magnetic (B) fields in electrochemical reactions.
      The probably best understood effect of B fields during electrochemical reactions
      is the magnetohydrodynamic (MHD) effect. In the majority of cases it manifests
      itself in increased mass transport rates which are a direct consequence of
      Lorentz forces in the bulk of the electrolyte. This enhanced mass transport can
      directly affect the electrocrystallization. The partial currents for the
      nucleation of nickel in magnetic fields were determined using an in situ micro
      gravimetric technique and are discussed on the basis of the nucleation model of
      Heerman and Tarallo. Another focus of the paper is the numerical simulation of
      MHD effects on electrochemical metal depositions. A careful analysis of the
      governing equations shows that many MHD problems must be treated in a 3D
      geometry. In most cases there is a complex interplay of natural and magnetically
      driven convection.

PMID- 27877961
TI  - Chirality of magneto-electrodeposited metal film electrodes.
AB  - The chiral electrode behaviors of magneto-electrodeposited (MED) Ag and Cu films
      were examined for the electrochemical reactions of D-glucose, L-glucose and L
      cysteine. The Ag and Cu films were electrodeposited under a magnetic field of 2 T
      parallel (+2 T) or antiparallel (-2 T) to the faradaic current. For MED films of
      both Ag and Cu, the oxidation current of L-glucose was larger than that of D
      glucose on the +2 T-film electrodes, and the results were opposite on the - 2 T
      film electrodes. These facts demonstrate that the MED metal films possess the
      ability of chiral recognition for D- and L-glucoses. The MED Ag film electrodes
      also exhibited chiral behavior for the oxidation of L-cysteine.

PMID- 27877960
TI  - Magnetic field effects on electric behavior of [Fe(CN)6]3- at bare and membrane
      coated electrodes.
AB  - The cyclic voltammetric behavior of [Fe(CN)6]3- was investigated under
      homogeneous magnetic fields perpendicular to the electrode surface in order to
      determine the effects of magnetic fields on the distribution of an Fe2+/Fe3+
      redox couple. The cathodic current was enhanced much more than the anodic current
      by a homogeneous magnetic field, suggesting that the concentration gradient of
      paramagnetic [Fe(CN)6]3- and diamagnetic [Fe(CN)6]4- formed at an electrode
      surface may also contribute to the asymmetric current. The apparent diffusion
      coefficient of the redox couple increased by over 30% in both cathodic and anodic
      processes upon applying a magnetic field. For a gold electrode coated with
      dioctadecyldimethylammonium, the application of a magnetic field perpendicular to
      the surface increased the peak-to-peak separation, and enhanced the asymmetric
      current. It is inferred that the application of a magnetic field promotes the
      electron-tunneling process by tilting chain molecules in the barrier membrane.

PMID- 27877962
TI  - In situ observation of magnetic orientation process of feeble magnetic materials
      under high magnetic fields.
AB  - An in situ microscopic observation of the magnetic orientation process of feeble
      magnetic fibers was carried out under high magnetic fields of up to 10 T using a
      scanning laser microscope. In the experiment, carbon fibers and needle-like
      titania fibers with a length of 1 to 20 MUm were used. The fibers were observed
      to gradually orient their axes parallel to the direction of the magnetic field.
      The orientation behavior of the sample fibers was evaluated on the basis of the
      measured duration required for a certain angular variation. As predicted from the
      theoretical consideration, it was confirmed that the duration required for a
      certain angular variation normalized by the viscosity of the fluid is described
      as a function of the fiber length. The results obtained here appear useful for
      the consideration of the magnetic orientation of materials suspended in a static
      fluid.

PMID- 27877963
TI  - Magnetic alignment and patterning of cellulose fibers.
AB  - The alignment and patterning of cellulose fibers under magnetic fields are
      reported. Static and rotating magnetic fields were used to align cellulose fibers
      with sizes ranging from millimeter to nanometer sizes. Cellulose fibers of the
      millimeter order, which were prepared for papermaking, and much smaller fibers
      with micrometer to nanometer sizes prepared by the acid hydrolysis of larger ones
      underwent magnetic alignment. Under a rotating field, a uniaxial alignment of
      fibers was achieved. The alignment was successfully fixed by the
      photopolymerization of a UV-curable resin precursor used as matrix. A monodomain
      chiral nematic film was prepared from an aqueous suspension of nanofibers. Using
      a field modulator inserted in a homogeneous magnetic field, simultaneous
      alignment and patterning were achieved.

PMID- 27877964
TI  - Magnetic orientation of single-walled carbon nanotubes or their composites using
      polymer wrapping.
AB  - The magnetic orientation of single-walled carbon nanotubes (SWNTs) or the SWNT
      composites wrapped with polymer using poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4
      phenylene vinylene] (MEHPPV) as the conducting polymer were examined. The
      formation of SWNT/MEHPPV composites was confirmed by examining absorption and
      fluorescence spectra. The N,N-dimethylformamide solution of SWNT/MEHPPV
      composites or the aqueous solution of the shortened SWNTs was introduced dropwise
      onto a mica or glass plate. The magnetic processing of the composites or the
      SWNTs was carried out using a superconducting magnet with a horizontal direction
      (8 T). The AFM images indicated that the SWNT/MEHPPV composites or the SWNTs were
      oriented randomly without magnetic processing, while with magnetic processing (8
      T), they were oriented with the tube axis of the composites or the SWNTs parallel
      to the magnetic field. In polarized absorption spectra of SWNT/MEHPPV composites
      on glass plates without magnetic processing, the absorbance due to semiconducting
      SWNT in the near-IR region in horizontal polarized light was almost the same as
      that in vertical polarized light. In contrast, with magnetic processing (8 T),
      the absorbance due to semiconducting SWNT in the horizontal polarization
      direction against the direction of magnetic field was stronger than that in the
      vertical polarization direction. Similar results were obtained from the polarized
      absorption spectra for the shortened SWNTs. These results of polarized absorption
      spectra also support the magnetic orientation of the SWNT/MEHPPV composites or
      the SWNTs. On the basis of a comparison of the composites and the SWNTs alone,
      the magnetic orientation of SWNT/MEHPPV composites is most likely ascribable to
      the anisotropy in susceptibilities of SWNTs.

PMID- 27877965
TI  - Anisotropic elasticity of magnetically ordered agarose gel.
AB  - The physical properties of agarose gel prepared under strong magnetic fields were
      investigated. The storage modulus was measured by the reflection method with an
      ultrasonic pulse. The measurement results of the gel's elasticity indicate that
      agarose gel has anisotropic properties. The elasticity and its anisotropy depend
      on the concentration of the gel and the magnetic field to which it is exposed.
      The experimental results indicate that the anisotropic network structure of the
      gel is induced by the exposure to the magnetic field during gelation. The
      gelation mechanism under a magnetic field is discussed.

PMID- 27877967
TI  - Observations of cellular responses to diamagnetic forces acting on cell
      components.
AB  - The magnetooptical measurements of the properties of living cells have a
      potentially large impact on cellular engineering and biotechnology because the
      noninvasive approach to applying magnetic fields on cells enables the detection
      of the dynamics of intracellular components under natural conditions. In this
      study, we examine a magnetooptical response in smooth muscle cells exposed to a
      vertical magnetic field of 5 T. The time course of the linearly polarized light
      transmittance of cells showed both a gradual decrease and fluctuations during
      exposure at 5 T. Real-time observations of smooth muscle cells and giant rodlike
      vesicles revealed that magnetic fields cause morphological changes in the cells
      and vesicles. In addition, results of the optical transmittance measurement of a
      fish scale indicate that cellular or tissue components are diamagnetically
      reoriented by magnetic fields.

PMID- 27877966
TI  - Magnetic susceptibility measurement of single iron/cobalt carbonyl microcrystal
      by atmospheric magnetophoresis.
AB  - In this study, the use of an innovative atmospheric magnetophoresis, which
      enables us to measure the mass magnetic susceptibility and mass of a
      microparticle simultaneously, was demonstrated. Using this technique, we
      determined the magnetic susceptibility of a crystalline deposit of iron/cobalt
      carbonyl, mainly composed of Fe2(CO)9, which was prepared photochemically from a
      gaseous mixture of iron pentacarbonyl (Fe(CO)5) and cobalt tricarbonyl nitrosyl
      (Co(CO)3NO). The mass magnetic susceptibility and the characteristic relaxation
      time of the microcrystal were (7.0+/-1.9)*10-9 m3 kg-1 and (5.6+/-2.2)*10-4 s,
      respectively. The observed magnetic susceptibility shows that the microparticle
      was paramagnetic. Assuming that the density was equal to that of Fe2(CO)9
      (2.1*103 kg m-3) and that the shape of the particle was spherical, a hydrodynamic
      radius of 4.7 MUm and a mass of 0.91 ng were observed. It was suggested that Co
      was incorporated in Fe2(CO)9.

PMID- 27877969
TI  - Effects of various poisoning compounds on the activity and stereospecificity of
      heterogeneous Ziegler-Natta catalyst.
AB  - A TiCl4/ethylbenzoate/MgCl2 Ziegler-Natta catalyst was pretreated with chemically
      different poisoning compounds to investigate their effects on the catalyst
      activity and stereospecificity for propylene polymerization. The poisoning power
      on the activity was in the order of methanol > acetone > ethyl acetate. A kinetic
      analysis using the stopped-flow method revealed that addition of the poisoning
      materials decreased the activity through the reduction of the number of active
      sites, whereas the catalyst isospecificity was hardly affected by these
      materials.

PMID- 27877968
TI  - Degradation behavior of polymer blend of isotactic polypropylenes with and
      without unsaturated chain end group.
AB  - In this work, the relationship between the unsaturated chain end group content
      and the thermal oxidative degradation rate was systematically studied with binary
      polymer blends of isotactic polypropylene (iPP) with and without the unsaturated
      chain end group. The iPPs with and without the unsaturated chain end group were
      synthesized by a metallocene catalyst in the absence of hydrogen and by a Ziegler
      catalyst in the presence of one, respectively. The thermal oxidative degradation
      rate of the binary iPP blends was estimated from the molecular weight and the
      apparent activation energy (DeltaE), which were obtained through size exclusion
      chromatography (SEC) and thermogravimetric analysis (TGA) measurements,
      respectively. These values exhibited a negative correlation against the mole
      content of the unsaturated chain end group. The thermal oxidative degradation
      rate apparently depends on the content of the unsaturated chain end group. This
      tendency suggests that the unsaturated chain end acts as a radical initiator of
      the iPP degradation reaction.

PMID- 27877970
TI  - The stability of polysiloxanes incorporating nano-scale physical property
      modifiers.
AB  - Reported here is the synthesis and subsequent characterization of the physical
      and chemical properties of novel polysiloxane elastomers modified with a series
      of polyhedraloligomericsilsequioxane (POSS) molecular silicas. The physical
      properties of the formulated nanocomposite systems have been characterized with a
      combination of dynamic mechanical analysis (DMA), broadband dielectric
      spectroscopy (BDS) and confocal Raman microscopy. The results of the physical
      property characterization demonstrate that the incorporation of low levels (1-4%
      by wt.) of POSS particles into the polysiloxane network leads to significant
      improvements in the mechanical properties of the elastomer and significantly
      alters the motional chain dynamics of the system as a whole. The results of
      studies performed to assess the long-term stability of these novel nanocomposite
      systems have demonstrated that POSS physical property modifiers can significantly
      alter the thermal stability of polysiloxane elastomers. Physically dispersed POSS
      has also been shown in some cases to be both mobile and disruptive within the
      polysiloxane networks, agglomerating into domains on a micron scale and migrating
      to the surface of the elastomers. This work demonstrates both the potential of
      POSS nanoparticles as physical property modifiers and describes the effects of
      POSS on the physical and chemical stability of polysiloxane systems.

PMID- 27877971
TI  - Effect of microstructure on the thermo-oxidation of solid isotactic polypropylene
      based polyolefins.
AB  - In the present work we aim to clarify the role of the microstructure and the
      crystalline distribution from the thermo-oxidation of solid isotactic PP (iPP)
      and ethylene-propylene (EP) copolymers. The effects of the content and quality of
      the isotacticity interruptions, together with the associated average isotactic
      length, on the induction time (ti) as well as on the activation energy (Eact) of
      the thermo-oxidation are analysed. Both parameters have been found to change
      markedly at an average isotactic length (n1) of 30 propylene units. While ti
      reaches a minimum when n1 is approximately 30 units, Eact increases quasi
      exponentially as the number of units decreases from 30. This variation can be
      explained in terms of changes induced in the crystalline interphase, i.e. local
      molecular dynamics, which are closely linked to the initiation of the thermo
      oxidation of isotactic PP-based polyolefins.

PMID- 27877972
TI  - Electronic structures of one-dimensional poly-fused selenophene radical cations:
      density functional theory study.
AB  - Hybrid density functional theory (DFT) calculations have been carried out for
      neutral and radical cation species of a fused selenophene oligomer, denoted by
      Se(n), where n represents the number of selenophene rings in the oligomer, to
      elucidate the electronic structures at ground and low-lying excited states. A
      polymer of fused selenophene was also investigated using one-dimensional periodic
      boundary conditions (PBC) for comparison. It was found that the reorganization
      energy of a radical cation of Se(n) from a vertical hole trapping point to its
      relaxed structure is significantly small. Also, the reorganization energy
      decreased gradually with increasing n, indicating that Se(n) has an effective
      intramolecular hole transport property. It was found that the radical cation
      species of Se(n) has a low-energy band in the near-IR region, which is strongly
      correlated to hole conductivity. The relationship between the electronic states
      and intramolecular hole conductivity was discussed on the basis of theoretical
      calculations.

PMID- 27877973
TI  - Durability of crosslinked polydimethylsyloxanes: the case of composite
      insulators.
AB  - Most applications of silicones are linked to their hydrophobic properties and
      (or) their high resistance to ageing (e.g. thermal ageing and photoageing).
      However, when placed in extreme environments, these materials can fail as in the
      case of epoxy/fiber glass composite powerlines insulators, where crosslinked
      polymethylsyloxanes (PDMSs) are used as the protective envelope (housing) of the
      insulator. We report on the behavior of both pure/noncrosslinked PDMSs and
      typical formulations used in industrial insulators, i.e. containing peroxide
      crosslinked PDMS, alumina trioxide hydrated (ATH) and silica. Special attention
      is paid on both (i) the sources of potential degradation and (ii) the best
      analytical methods that can be applied to the study of very complex formulations.
      (i) Aside from conventional types of ageing such as photo-ageing and thermal,
      hydrolytic, and service life ageings, treatments with acidic vapors, plasma and
      ozone possibly generating species from the reaction of a high electric field with
      air were also performed, which allowed to accelerate electrical and out-door
      ageings and to obtain differently aged materials. (ii) Aside from conventional
      analytical methods of polymer degradation such as FTIR/ATR spectroscopy and SEC,
      TG, hardness measurements, more specific methods like photo/DSC, TG/IR,
      thermoporosimetry, resistivity and density measurements were also performed to
      characterize the chemical and physical evolutions of polymer materials. In
      particular, it was found that treatment with nitric acid vapor has detrimental
      effects on the properties of both fire retardants (e.g. ATH) and PDMSs, affecting
      the hardness and resistivity of the formulated material.

PMID- 27877974
TI  - Inhibition of Alzheimer amyloid beta aggregation by polyvalent trehalose.
AB  - A glycopolymer carrying trehalose was found to suppress the formation of amyloid
      fibrils from the amyloid beta peptide (1-42) (Abeta), as evaluated by thioflavin
      T assay and atomic force microscopy. Glycopolymers carrying sugar alcohols also
      changed the aggregation properties of Abeta, and the inhibitory effect depended
      on the type of sugar and alkyl side chain. Neutralization activity was confirmed
      by in vitro assay using HeLa cells. The glycopolymer carrying trehalose strongly
      inhibited amyloid formation and neutralized cytotoxicity.

PMID- 27877975
TI  - Effect of clays on the fire-retardant properties of a polyethylenic copolymer
      containing intumescent formulation.
AB  - Organophilic clay particles were added to a standard intumescent formulation and,
      since the role of clay expansion or intercalation is still a matter of much
      controversy, several clays with varying degrees of interlayer distances were
      evaluated. The composites were obtained by blending the nanostructured clay and
      the intumescent system with a polyethylenic copolymer. The flame-retardant
      properties of the materials were evaluated by the limiting oxygen index (LOI),
      the UL-94 rating and thermogravimetric analysis (TGA). The results showed that
      the addition of highly expanded clays to the ammonium polyphosphate and
      pentaerythritol formulation does not significantly increase the flame retardancy
      of the mixture, when measured by the LOI and UL-94. However, when clays with
      smaller basal distances were added to the intumescent formulation, a synergistic
      effect was observed. In contrast, the simple addition of clays to the copolymer,
      without the intumescent formulation, did not increase the fire retardance of the
      materials.

PMID- 27877976
TI  - Investigation of the liquid crystal alignment layer: effect on electrical
      properties.
AB  - We investigate the electrical behavior of a symmetric liquid crystal (LC) cell:
      elecrode-silane-LC-silane-electrode. The silane (chlorodimethyloctadecyl-silane)
      layer induces a homeotropic orientation of the nematic liquid crystal (NLC)
      molecules. The wettability technique is used to detect the change of the surface
      energy of the electrode upon cleaning and silane layer deposition. We report on
      the dynamic impedance measurements of the nematic liquid crystal cell. It is
      found that the silane alignment layer has a blocking effect on the liquid crystal
      (LC) cell. We also study the relaxation behavior of the cell which is later
      assimilated as an electrical equivalent circuit.

PMID- 27877977
TI  - Microstructure and corrosion characteristics of laser-alloyed magnesium alloy
      AZ91D with Al-Si powder.
AB  - Blown-powder laser surface alloying was performed on the magnesium alloy AZ91D
      with Al-Si alloy powder to improve corrosion resistance. Characterization by
      scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and x
      ray diffraction (XRD) analysis revealed that intermetallic compounds (IMCs) of
      Mg2Si, Al12Mg17 and Al3Mg2 were formed in the matrix of alpha-Mg and Al solid
      solutions in Al-Si alloyed layers. The anodic polarization test in 3.5% NaCl
      aqueous solution showed that preferential corrosion occurred in the alpha-Mg
      matrix of the AZ91D base metal. The Al-Si alloyed layers exhibited a lower
      corrosion rate and a higher polarization resistance than AZ91D. The compactly
      dispersed dendritic Mg2Si phase, and the dendritic and angular phases of Al12Mg17
      and Al3Mg2 in the alloyed microstructure were observed to be corrosion-resistant,
      constituting a barrier that retards corrosion. Corrosion initiated at the
      interface between IMCs and the solid solution matrix, and at substructures of the
      matrix, subsequently pervaded into the surrounding microstructure.

PMID- 27877978
TI  - Textural, structural and electrical properties of TiO2 nanoparticles using Brij
      35 and P123 as surfactants.
AB  - The effect of the use of the triblock copolymer Pluronic
      P123[(PEO)20(PPO)70(PEO)20, Aldrich] and the non-ionic polyoxyethylene-lauryl
      ether Brij 35 as surfactants on the textural, structural and electrical
      properties of nanosized TiO2 is analyzed in this work. The as-obtained samples
      were thermally treated at 400  degrees C to eliminate the surfactant, promote
      dehydroxylation and crystallize the sample. The TiO2 samples were characterized
      by thermal analysis, N2 physisorption, x-ray diffraction analysis, micro-Raman
      spectroscopy and scanning electron microscopy. To evaluate the TiO2 electrical
      features, I-V data were obtained. The x-ray diffraction results show that in the
      chemical synthesis using surfactants, the crystallite size is smaller than that
      of the commercial sample. The Raman spectroscopy results clearly indicate that,
      when P123 is used, the anatase phase of TiO2 is obtained, whereas when Brij 35 is
      used a mixture of the anatase and brookite phases is obtained. The specific
      surface area and crystallite size of the TiO2 prepared as indicated above are
      higher and smaller, respectively, than the corresponding properties found in
      commercial TiO2. The I-V plot showed a nonlinear behavior of the nanosized TiO2.
      The samples obtained with P123 showed the best electrical conductivity.

PMID- 27877979
TI  - BiFeO3-doped (Na0.5K0.5)NbO3 lead-free piezoelectric ceramics.
AB  - Lead-free piezoelectric ceramics (1-x)(Na0.5K0.5)NbO3-xBiFeO3 (x=0~0.07) were
      synthesized by the solid-state reaction. Differential scanning calorimetry (DSC)
      measurements revealed that an increase in the amount of BiFeO3 dopant resulted in
      a decrease in the orthorhombic-tetragonal and tetragonal-cubic phase transition
      temperature of the material. One percent BiFeO3 additive suppressed grain growth,
      which not only benefits the sintering of ceramics but also enhances the
      piezoelectric and ferroelectric properties, where d33=145pC/N, kp=0.31, Qm=80,
      Pr=11.3 MUC cm-2 and Ec=16.5 kV cm-1. As xBF>0.01, both piezoelectric and
      ferroelectric properties decreased rapidly with an increasing amount of dopant.

PMID- 27877980
TI  - Effect of environment on corrosion characteristics of newly developed DMR-1700
      structural steel.
AB  - The corrosion resistance of any metallic material depends on the environment to
      which it is exposed. DMR-1700 steel is a material for structural applications
      that has been recently developed at Defence Metallurgical Research Laboratory by
      changing the chemistry of alloying elements. Therefore, a detailed understanding
      of its corrosion characteristics under different environmental conditions is
      essential. In the present paper, we report the results of a systematic corrosion
      study that was carried out on the new steel to determine the effect of the
      environment on the protective nature of the oxide scale that forms on its surface
      under different environmental conditions. Furthermore, the oxide scale as well as
      the resistance to pitting and crevice corrosion were studied in various
      environments. The surface morphologies of the corroded steels were observed under
      a scanning electron microscope (SEM) to determine the nature of the corrosion. On
      the basis of studies by different techniques, DMR-1700 steel is recommended for
      the manufacture of components used in various systems in conjunction with the
      application of an appropriate protective coating to improve its resistivity to
      corrosion.

PMID- 27877981
TI  - Stable superhydrophobic surface: fabrication of interstitial cottonlike structure
      of copper nanocrystals by magnetron sputtering.
AB  - A stable superhydrophobic copper surface was obtained by radio-frequency magnetic
      sputtering on Si (100) and quartz substrates. The water contact angle and sliding
      angle of the superhydrophobic copper surface were 160.5 degrees  and 3+/-1.9
      degrees , respectively. Scanning electron microscopy (SEM) photos show that the
      superhydrophobic surface structure comprises many uniform nanocrystals with a
      diameter of about 100 nm. A brief explanation of the formation of this special
      microstructure and the mechanism of its wettability were proposed.

PMID- 27877982
TI  - Phase formation in selected surface-roughened plasma-nitrided 304 austenite
      stainless steel.
AB  - Direct current (DC) glow discharge plasma nitriding was carried out on three
      selected surface-roughened AISI 304 stainless steel samples at 833 K under 4 mbar
      pressures for 24 h in the presence of N2:H2 gas mixtures of 50 : 50 ratios. After
      plasma nitriding, the phase formation, case depth, surface roughness, and
      microhardness of a plasma-nitrided layer were evaluated by glancing angle x-ray
      diffractogram, optical microscope, stylus profilometer, and Vickers microhardness
      tester techniques. The case depth, surface hardness, and phase formation
      variations were observed with a variation in initial surface roughness. The
      diffraction patterns of the plasma-nitrided samples showed the modified
      intensities of the alpha and gamma phases along with those of the CrN, Fe4N, and
      Fe3N phases. Hardness and case depth variations were observed with a variation in
      surface roughness. A maximum hardness of 1058 Hv and a case depth of 95 MUm were
      achieved in least surface-roughened samples.

PMID- 27877983
TI  - On cavitation and macroscopic behaviour of amorphous polymer-rubber blends.
AB  - The macroscopic behaviour of rubber-modified polymethyl methacrylate (PMMA) was
      investigated by taking into account the microdeformation mechanisms of rubber
      cavitation. The dependence of the macroscopic stress-strain behaviour of matrix
      deformation on the cavitation of rubber particles was discussed. A
      phenomenological elastic-viscoplastic model was used to model the behaviour of
      the matrix material, while the rubber particles were modelled with the
      hyperelasticity theory. A two-phase composite material with a periodic
      arrangement of reinforcing particles of a circular unit cell section was
      considered. Finite-element analysis was used to determine the local stresses and
      strains in the two-phase composite. In order to describe the cavitation of the
      rubber particles, a criterion of void nucleation is implemented in the finite
      element (FE) code. A comparison of the numerically predicted response with
      experimental result indicates that the numerical homogenisation analysis gives
      satisfactory prediction results.

PMID- 27877984
TI  - Growth of ZnO nanowires on nonwoven polyethylene fibers.
AB  - We report the growth of ZnO nanowires on nonwoven polyethylene fibers using a
      simple hydrothermal method at a temperature below the boiling point of water. The
      ZnO nanowires were grown from seed ZnO nanoparticles affixed onto the fibers. The
      seed ZnO nanoparticles, with diameters of about 6-7 nm, were synthesized in
      isopropanol by reducing zinc acetate hydrate with sodium hydroxide. The growth
      process was carried out in a sealed chemical bath containing an equimolar
      solution of zinc nitrate hexahydrate and hexamethylene tetramine at a temperature
      of 95  degrees C over a period of up to 20 h. The thickness and length of the
      nanowires can be controlled by using different concentrations of the starting
      reactants and growth durations. A 0.5 mM chemical bath yielded nanowires with an
      average diameter of around 50 nm, while a 25 mM bath resulted in wires with a
      thickness of up to about 1 MUm. The length of the wires depends both on the
      concentration of the precursor solution as well as the growth duration, and in 20
      h, nanowires as long as 10 MUm can be grown. The nonwoven mesh of polyethylene
      fibers covered with ZnO nanowires can be used for novel applications such as
      water treatment by degrading pollutants by photocatalysis. Photocatalysis tests
      carried out on standard test contaminants revealed that the polyethylene fibers
      with ZnO nanowires grown on them could accelerate the photocatalytic degradation
      process by a factor of 3.

PMID- 27877985
TI  - Synthesis, characterization and properties of polyaniline/expanded vermiculite
      intercalated nanocomposite.
AB  - The synthesis characterization and conductivities of polyaniline/expanded
      vermiculite intercalated nanocomposite are presented in this paper. The
      conductive emeraldine salt form of polyaniline is inserted into the interlayer of
      expanded vermiculite to produce the nanocomposite with high conductivity. The
      structures and properties are characterized by transmission electron microscopy x
      ray diffraction spectroscopy fourier transform infrared spectroscopy
      thermogravimetry analysis and by the measurements of conductivity and stability.
      The results show that an intercalated nanocomposite with high conductivity and
      stability is obtained. The synthesis conditions are optimized to obtain the
      highest conductivity which is 6.80 S cm-1.

PMID- 27877986
TI  - Application of microcapsulation technology to the preparation of carbon foam.
AB  - Microcapsules were prepared by in situ polymerization and microcapsulation.
      Tetraethyl orthosilicate was used as the core material and phenolic resin was
      used as the wall material in an emulsion system of polyacrylic and tetraethyl
      orthosilicate. The obtained microcapsules were slowly heated such that the core
      material was released by evaporation, leaving hollow-core spheres. The spheres
      were mixed with a phenolic resin-derived binder and molded to obtain a carbon
      foam precursor, which was carbonized at 1100  degrees C under the protection of
      N2 gas and graphitized at 2300  degrees C under the protection of Ar gas. Thus,
      the carbon foam of hollow closed-shelled microspheres with a graphitic structure
      was prepared. The properties and structure of this foam were discussed.

PMID- 27877987
TI  - Crystal growth and structure of L-methionine L-methioninium hydrogen maleate-a
      new NLO material.
AB  - A new organic nonlinear optical (NLO) crystal from the amino acid family, viz., L
      methionine L-methioninium hydrogen maleate (LMMM), has been grown by slow
      evaporation method from aqueous solution. Bulk crystals were grown using
      submerged seed solution method. The structure was elucidated using the single
      crystal x-ray diffraction data. The compound crystallized in the space group P21
      and the unit cell contains a protonated L-methioninium cation and a zwitterionic
      methionine residue plus a maleate anion. The backbone conformation angles Psi1
      and Psi2 are in cis and trans configurations for both the methionine and
      methioninium residues, respectively. Amino and carboxyl groups of the
      methioninium and methionine residues are connected through N-H...O hydrogen bonds
      leading to a ring R22(10) motif.

PMID- 27877988
TI  - An innovative energy-saving in-flight melting technology and its application to
      glass production.
AB  - The conventional method used for glass melting is air-fuel firing, which is
      inefficient, energy-intensive and time-consuming. In this study, an innovative in
      flight melting technology was developed and applied to glass production for the
      purposes of energy conservation and environmental protection. Three types of
      heating sources, radio-frequency (RF) plasma, a 12-phase alternating current (ac)
      arc and an oxygen burner, were used to investigate the in-flight melting behavior
      of granulated powders. Results show that the melted particles are spherical with
      a smooth surface and compact structure. The diameter of the melted particles is
      about 50% of that of the original powders. The decomposition and vitrification
      degrees of the prepared powders decrease in the order of powders prepared by RF
      plasma, the 12-phase ac arc and the oxygen burner. The largest heat transfer is
      from RF plasma to particles, which results in the highest particle temperature
      (1810  degrees C) and the greatest vitrification degree of the raw material. The
      high decomposition and vitrification degrees, which are achieved in milliseconds,
      shorten the melting and fining times of the glass considerably. Our results
      indicate that the proposed in-flight melting technology is a promising method for
      use in the glass industry.

PMID- 27877989
TI  - Investigation of low-resistivity from hydrogenated lightly B-doped diamond by ion
      implantation.
AB  - We have implanted boron (B) ions (dosage: 5*1014 cm-2) into diamond and then
      hydrogenated the sample by implantating hydrogen ions at room temperature. A p
      type diamond material with a low resistivity of 7.37 mOmega cm has been obtained
      in our experiment, which suggests that the hydrogenation of B-doped diamond
      results in a low-resistivity p-type material. Interestingly, inverse annealing,
      in which carrier concentration decreased with increasing annealing temperature,
      was observed at annealing temperatures above 600  degrees C. In addition, the
      formation mechanism of a low-resistivity material has been studied by density
      functional theory calculation using a plane wave method.

PMID- 27877990
TI  - Fine structure characterization of zero-valent iron nanoparticles for
      decontamination of nitrites and nitrates in wastewater and groundwater.
AB  - The main objectives of the present study were to investigate the chemical
      reduction of nitrate or nitrite species by zero-valent iron nanoparticle (ZVIN)
      in aqueous solution and related reaction kinetics or mechanisms using fine
      structure characterization. This work also exemplifies the utilization of field
      emission-scanning electron microscope (FE-SEM), transmission electron microscopy
      (TEM), and x-ray diffraction (XRD) to reveal the speciation and possible reaction
      pathway in a very complex adsorption and redox reaction process. Experimentally,
      ZVIN of this study was prepared by sodium borohydride reduction method at room
      temperature and ambient pressure. The morphology of as-synthesized ZVIN shows
      that the nearly ball and ultrafine particles ranged of 20-50 nm were observed
      with FE-SEM or TEM analysis. The kinetic model of nitrites or nitrates reductive
      reaction by ZVIN is proposed as a pseudo first-order kinetic equation. The
      nitrite and nitrate removal efficiencies using ZVIN were found 65-83% and 51-68%,
      respectively, based on three different initial concentrations. Based on the XRD
      pattern analyses, it is found that the quantitative relationship between nitrite
      and Fe(III) or Fe(II) is similar to the one between nitrate and Fe(III) in the
      ZVIN study. The possible reason is due to the faster nitrite reduction by ZVIN.
      In fact, the occurrence of the relative faster nitrite reductive reaction
      suggested that the passivation of the ZVIN have a significant contribution to
      iron corrosion. The extended x-ray absorption fine structure (EXAFS) or x-ray
      absorption near edge structure (XANES) spectra show that the nitrites or nitrates
      reduce to N2 or NH3 while oxidizing the ZVIN to Fe2O3 or Fe3O4 electrochemically.
      It is also very clear that decontamination of nitrate or nitrite species in
      groundwater via the in-situ remediation with a ZVIN permeable reactive barrier
      would be environmentally attractive.

PMID- 27877991
TI  - Characterization of ITO/CdO/glass thin films evaporated by electron beam
      technique.
AB  - A thin buffer layer of cadmium oxide (CdO) was used to enhance the optical and
      electrical properties of indium tin oxide (ITO) films prepared by an electron
      beam evaporation technique. The effects of the thickness and heat treatment of
      the CdO layer on the structural, optical and electrical properties of ITO films
      were carried out. It was found that the CdO layer with a thickness of 25 nm
      results in an optimum transmittance of 70% in the visible region and an optimum
      resistivity of 5.1*10-3 Omega cm at room temperature. The effect of heat
      treatment on the CdO buffer layer with a thickness of 25 nm was considered to
      improve the optoelectronic properties of the formed ITO films. With increasing
      annealing temperature, the crystallinity of ITO films seemed to improve,
      enhancing some physical properties, such as film transmittance and conductivity.
      ITO films deposited onto a CdO buffer layer heated at 450  degrees C showed a
      maximum transmittance of 91% in the visible and near-infrared regions of the
      spectrum associated with the highest optical energy gap of 3.61 eV and electrical
      resistivity of 4.45*10-4 Omega cm at room temperature. Other optical parameters,
      such as refractive index, extinction coefficient, dielectric constant, dispersion
      energy, single effective oscillator energy, packing density and free carrier
      concentration, were also studied.

PMID- 27877992
TI  - Study of superconducting state parameters of ternary metallic glasses through
      pseudopotential approach.
AB  - A theoretical investigation on the screening dependence of the superconducting
      state parameters (SSPs) viz. the electron-phonon coupling strength lambda, the
      Coulomb pseudopotential MU*, the transition temperature TC, the isotope effect
      exponent alpha and the effective interaction strength N0V of some ternary
      metallic glasses such as Ti50Be34Zr10, (Mo0.6Ru0.4)78B22, (Mo0.6Ru0.4)80B20,
      (Mo0.4Ru0.6)80P20, (Mo0.6Ru0.4)70Si30, (Mo0.6Ru0.4)84B16, (Mo0.6Ru0.4)72Si28,
      (Mo0.6Ru0.4)86B14, (Mo0.6Ru0.4)76Si24, (Mo0.6Ru0.4)78Si22, (Mo0.6Ru0.4)80Si20,
      (Mo0.6Ru0.4)82Si18 and (Mo0.6Ru0.4)80P20 is reported for the first time using
      Ashcroft's empty core (EMC) model potential. Five local field correction
      functions proposed by Hartree (H), Taylor (T), Ichimaru-Utsumi (IU), Farid et al
      (F) and Sarkar et al (S) are used in the present investigation to study the
      effect of screening on the aforesaid properties. It is observed that lambda and
      TC are reasonably sensitive to the selection of the local field correction
      functions, whereas MU*, alpha and N0V show weak dependences on the local field
      correction functions. The transition temperature TC obtained from the H-local
      field correction function is found to be in excellent agreement with available
      experimental data. Also, the present results are found to be in qualitative
      agreement with other earlier reported data, which confirms the existence of the
      superconducting phase in the above ternary metallic glasses.

PMID- 27877993
TI  - Layer-by-layer assembly of imogolite nanotubes and polyelectrolytes into core
      shell particles and their conversion to hierarchically porous spheres.
AB  - Core-shell particles were prepared by the layer-by-layer (LbL) assembly of
      imogolite (IMO) nanotubes and poly(sodium 4-styrenesulfonate) (PSS) on
      polystyrene particles (diameter: 800 nm) coated preliminarily with
      poly(diallyldimethylammonium chloride) (PDDA). PSS and imogolite were alternately
      adsorbed on the particles to form core-shell particles with one to three bilayers
      of PSS/IMO. Macroporous hollow spheres were formed by removing polystyrene cores
      via heat treatment or extraction when the number of bilayers was 2 or 3. The
      sample formed by extraction (the number of bilayer was 3) showed only
      macroporosity and PSS remained in the shell, whereas the heat-treated sample
      showed hierarchical micro- and macroporosities. When the diameter of polystyrene
      particles decreased from 800 nm to 300 or 100 nm, hollow spheres were deformed
      because of the increase in the relative length of imogolite nanotubes against the
      size of polystyrene particles. Imogolite is a promising building block of
      hierarchically porous materials with core-shell morphologies using LbL assembly.

PMID- 27877994
TI  - Fabrication of spintronics device by direct synthesis of single-walled carbon
      nanotubes from ferromagnetic electrodes.
AB  - We describe an alternative method for realizing a carbon nanotube spin field
      effect transistor device by the direct synthesis of single-walled carbon
      nanotubes (SWNTs) on substrates by alcohol catalytic chemical vapor deposition.
      We observed hysteretic magnetoresistance (MR) at low temperatures due to spin
      dependent transport. In these devices, the maximum ratio in resistance variation
      of MR was found to be 1.8%.

PMID- 27877995
TI  - Textured silicon nitride: processing and anisotropic properties.
AB  - Textured silicon nitride (Si3N4) has been intensively studied over the past 15
      years because of its use for achieving its superthermal and mechanical
      properties. In this review we present the fundamental aspects of the processing
      and anisotropic properties of textured Si3N4, with emphasis on the anisotropic
      and abnormal grain growth of beta-Si3N4, texture structure and texture analysis,
      processing methods and anisotropic properties. On the basis of the texturing
      mechanisms, the processing methods described in this article have been classified
      into two types: hot-working (HW) and templated grain growth (TGG). The HW method
      includes the hot-pressing, hot-forging and sinter-forging techniques, and the TGG
      method includes the cold-pressing, extrusion, tape-casting and strong magnetic
      field alignment techniques for beta-Si3N4 seed crystals. Each processing
      technique is thoroughly discussed in terms of theoretical models and experimental
      data, including the texturing mechanisms and the factors affecting texture
      development. Also, methods of synthesizing the rodlike beta-Si3N4 single crystals
      are presented. Various anisotropic properties of textured Si3N4 and their origins
      are thoroughly described and discussed, such as hardness, elastic modulus,
      bending strength, fracture toughness, fracture energy, creep behavior,
      tribological and wear behavior, erosion behavior, contact damage behavior and
      thermal conductivity. Models are analyzed to determine the thermal anisotropy by
      considering the intrinsic thermal anisotropy, degree of orientation and various
      microstructure factors. Textured porous Si3N4 with a unique microstructure
      composed of oriented elongated beta-Si3N4 and anisotropic pores is also described
      for the first time, with emphasis on its unique mechanical and thermal-mechanical
      properties. Moreover, as an important related material, textured alpha-Sialon is
      also reviewed, because the presence of elongated alpha-Sialon grains allows the
      production of textured alpha-Sialon using the same methods as those used for
      textured beta-Si3N4 and beta-Sialon.

PMID- 27877996
TI  - Warm spraying-a novel coating process based on high-velocity impact of solid
      particles.
AB  - In recent years, coating processes based on the impact of high-velocity solid
      particles such as cold spraying and aerosol deposition have been developed and
      attracting much industrial attention. A novel coating process called 'warm
      spraying' has been developed, in which coatings are formed by the high-velocity
      impact of solid powder particles heated to appropriate temperatures below the
      melting point of the powder material. The advantages of such process are as
      follows: (1) the critical velocity needed to form a coating can be significantly
      lowered by heating, (2) the degradation of feedstock powder such as oxidation can
      be significantly controlled compared with conventional thermal spraying where
      powder is molten, and (3) various coating structures can be realized from porous
      to dense ones by controlling the temperature and velocity of the particles. The
      principles and characteristics of this new process are discussed in light of
      other existing spray processes such as high-velocity oxy-fuel spraying and cold
      spraying. The gas dynamics of particle heating and acceleration by the spraying
      apparatus as well as the high-velocity impact phenomena of powder particles are
      discussed in detail. Several examples of depositing heat sensitive materials such
      as titanium, metallic glass, WC-Co cermet and polymers are described with
      potential industrial applications.

PMID- 27877997
TI  - Chemistry of layered d-metal pnictide oxides and their potential as candidates
      for new superconductors.
AB  - Layered d-metal pnictide oxides are a unique class of compounds which consist of
      characteristic d-metal pnictide layers and metal oxide layers. More than 100 of
      these layered compounds, including the recently discovered Fe-based
      superconducting pnictide oxides, can be classified into nine structure types.
      These structure types and the chemical and physical properties of the
      characteristic d-metal pnictide layers and metal oxide layers of the layered d
      metal pnictide oxides are reviewed and discussed. Furthermore, possible
      approaches to design new superconductors based on these layered d-metal pnictide
      oxides are proposed.

PMID- 27877998
TI  - Superhydrophobic cotton fabrics prepared by sol-gel coating of TiO2 and surface
      hydrophobization.
AB  - By coating fibers with titania sol to generate a dual-size surface roughness,
      followed by hydrophobization with stearic acid, 1H,1H,2H,2H
      perfluorodecyltrichlorosilane or their combination, hydrophilic cotton fabrics
      were made superhydrophobic. The surface wettability and topology of cotton
      fabrics were studied by contact angle measurement and scanning electron
      microscopy. The UV-shielding property of the treated fabrics was also
      characterized by UV-vis spectrophotometry.

PMID- 27878000
TI  - Effect of metal-ion-to-fuel ratio on the phase formation of bioceramic phosphates
      synthesized by self-propagating combustion.
AB  - Synthetic calcium hydroxyapatite (HAP, Ca10 (PO4)6 (OH)2) is a well-known
      bioceramic material used in orthopedic and dental applications because of its
      excellent biocompatibility and bone-bonding ability due to its structural and
      compositional similarity to human bone. Here we report, for the first time, the
      synthesis of HAP by combustion employing tartaric acid as a fuel. Calcium nitrate
      is used as the source of calcium and diammonium hydrogen phosphate serves as the
      source of phosphate ions. Reaction processing parameters such as the pH, fuel
      oxidant ratio and autoignition temperature are controlled and monitored. The
      products were characterized by powder x-ray diffraction, which revealed the
      formation of a hexagonal hydroxyapatite phase. Fourier transform infrared
      spectroscopy (FT-IR) spectra showed that the substitution of a carbonate ion
      occurs at the phosphate site. The morphology of the particles was imaged by
      scanning electron microscopy, which also revealed that the particles are of
      submicron size. Thermal analysis showed that the phase formation takes place at
      the time of combustion. Surface area and porosity analysis showed that the
      surface area is high and that the pores are of nanometer size. The mean grain
      size of the HAP powder, determined by the Debye-Scherrer formula, is in the range
      20-30 nm. Chemical analyses to determine the Ca : P atomic ratio in synthesized
      ceramics were performed, and it was found to be 1 : 1.66.

PMID- 27877999
TI  - Microstructure and corrosion resistance of Ni-based alloy laser coatings with
      nanosize CeO2 addition.
AB  - Micron-size Ni-base alloy (NBA) powders were mixed with both 1.5 wt.%
      (hereinafter %) micron-size CeO2 (m-CeO2) and also 1.5% and 3.0% nano-size CeO2
      (n- CeO2) powders. These mixtures were coated on low-carbon steel (Q235) by 2.0
      kW CO2 laser cladding. The effects on the microstructures, phases and
      electrochemical corrosion of the coatings upon the addition of m- and n- CeO2
      powders to NBA (m- and n- CeO2 /NBA) have been investigated. The results showed
      that a smooth coating was prepared under suitable processing parameters (P= 2.0
      kW, V= 180 mm min- 1) by adding 1.5% n- CeO2. In addition to the primary phases
      of gamma-Ni, Cr23C6 and Ni3B in the Ni-base alloy coating, CeNi3 was formed in Ni
      base alloy coatings with both n- CeO2 and m-CeO2 particles, and CeNi5 appeared in
      the coating upon decreasing the size of CeO2 particles. Well-developed dendrites
      were observed in the Ni-base alloy coating; directional dendrites grew at the
      interface in the coating upon the addition of m-CeO2, whereas fine and
      multioriented dendrites grew upon decreasing the size of CeO2 particles to the
      nanoscale. Actinomorphic dendrites and compact equiaxed dendrites grew from the
      interface to near the surface upon increasing the content of n- CeO2 from 1.5 to
      3.0%. In strongly acidic HNO3 solution, the severe corrosion of dendrites
      occurred and there were many corrosion pits in the Ni-base alloy coating;
      intercrystalline corrosion also has a dominant role upon the addition of m-CeO2,
      whereas uniform corrosion occurs in the coating as the size of CeO2 particles is
      decreased to nanoscale.

PMID- 27878001
TI  - Enhanced bioactivity of ZnO nanoparticles-an antimicrobial study.
AB  - In this study, we investigate the antibacterial activity of ZnO nanoparticles
      with various particle sizes. ZnO was prepared by the base hydrolysis of zinc
      acetate in a 2-propanol medium and also by a precipitation method using Zn(NO3)2
      and NaOH. The products were characterized by x-ray diffraction (XRD) analysis,
      transmission electron microscopy (TEM) and photoluminescence (PL) spectroscopy.
      Bacteriological tests such as minimum inhibitory concentration (MIC) and disk
      diffusion were performed in Luria-Bertani and nutrient agar media on solid agar
      plates and in liquid broth systems using different concentrations of ZnO by a
      standard microbial method for the first time. Our bacteriological study showed
      the enhanced biocidal activity of ZnO nanoparticles compared with bulk ZnO in
      repeated experiments. This demonstrated that the bactericidal efficacy of ZnO
      nanoparticles increases with decreasing particle size. It is proposed that both
      the abrasiveness and the surface oxygen species of ZnO nanoparticles promote the
      biocidal properties of ZnO nanoparticles.

PMID- 27878002
TI  - Formation of Al3Ti/Mg composite by powder metallurgy of Mg-Al-Ti system.
AB  - An in situ titanium trialuminide (Al3Ti)-particle-reinforced magnesium matrix
      composite has been successfully fabricated by the powder metallurgy of a Mg-Al-Ti
      system. The reaction processes and formation mechanism for synthesizing the
      composite were studied by differential scanning calorimetry (DSC), x-ray
      diffractometry (XRD), scanning electron microscopy (SEM) and energy-dispersive x
      ray spectroscopy (EDS). Al3Ti particles are found to be synthesized in situ in
      the Mg alloy matrix. During the reaction sintering of the Mg-Al-Ti system, Al3Ti
      particles are formed through the reaction of liquid Al with as-dissolved Ti
      around the Ti particles. The formed intermetallic particles accumulate at the
      original sites of the Ti particles. As sintering time increases, the accumulated
      intermetallic particles disperse and reach a relatively homogeneous distribution
      in the matrix. It is found that the reaction process of the Mg-Al-Ti system is
      almost the same as that of the Al-Ti system. Mg also acts as a catalytic agent
      and a diluent in the reactions and shifts the reactions of Al and Ti to lower
      temperatures. An additional amount of Al is required for eliminating residual Ti
      and solid-solution strengthening of the Mg matrix.

PMID- 27878003
TI  - A new route for preparation of sodium-silicate-based hydrophobic silica aerogels
      via ambient-pressure drying.
AB  - An in-depth investigation into the synthesis of hydrophobic silica aerogels
      prepared by the surface derivatization of wet gels followed by subsequent drying
      at ambient pressure is reported. The following sol-gel parameters were examined
      for their effect on the physical properties of the derived aerogels: number of
      gel washings with water, percentage of hexane or methanol in silylating mixture,
      molar ratio of tartaric acid: Na2SiO3, gel aging period, weight% of silica,
      trimethylchlorosilane (TMCS) percentage, and silylation period. These parameters
      were varied from 1 to 4, 0 to 100%, 0.27 to 1.2, 0 to 4 h, 1.5 to 8 wt.%, 20 to
      40% and 6 to 24 h, respectively. The properties of hydrophobic silica aerogels
      synthesized by this new route were investigated in terms of bulk density,
      percentage volume shrinkage, percentage porosity, thermal conductivity and
      contact angle with water, and by Fourier transform infrared spectroscopy (FTIR).
      The as-prepared hydrophobic silica aerogels exhibited high temperature stability
      (up to approximately 435  degrees C) as measured by
      thermogravimetric/differential thermal analysis (TGA-DTA). The optimal sol-gel
      parameters were found to be a molar ratio of Na2SiO3:H2O : tartaric acid : TMCS
      of 1 : 146.67 : 0.86 : 9.46, an aging period of 3 h, four washings with water in
      24 h and the use of a 50% hexane- or methanol-based silylating mixture. Aerogels
      prepared with these optimal parameters were found to exhibit 50% optical
      transparency in the visible range, 84 kg m-3 density, 0.090 W mK-1 thermal
      conductivity, 95% porosity and a contact angle of 146 degrees  with water.

PMID- 27878004
TI  - Optimization of growth conditions of ZnO nano thin films by chemical double dip
      technique.
AB  - Zinc oxide (ZnO) nano thin films have been deposited by the chemical double-dip
      technique using aqueous ZnSO4 and NaOH solutions. The ZnO films were
      characterized in terms of surface morphology by x-ray diffraction, energy
      dispersive x-ray analysis (EDX), the use of a scanning electron microscope (SEM)
      and atomic force microscope (AFM) for surface morphology. The films exhibited a
      smooth morphology. The chemical states of oxygen and zinc in the ZnO nano thin
      films were also investigated by x-ray photoelectron spectroscopy (XPS). In the
      present investigations, highly textured ZnO thin films with a preferential (002)
      orientation were prepared on glass substrates. The deposition conditions were
      optimized to obtain device-quality films for practical applications.

PMID- 27878005
TI  - Preparation of superhydrophobic surfaces on cotton textiles.
AB  - Superhydrophobic surfaces were fabricated by the complex coating of silica
      nanoparticles with functional groups onto cotton textiles to generate a dual-size
      surface roughness, followed by hydrophobization with stearic acid, 1H, 1H, 2H, 2H
      perfluorodecyltrichlorosilane or their combination. The wettability and
      morphology of the as-fabricated surfaces were investigated by contact angle
      measurement and scanning electron microscopy. Characterizations by transmission
      electron microscopy, Fourier transformation infrared spectroscopy, and thermal
      gravimetric analysis were also conducted.

PMID- 27878006
TI  - Combinatorial electrochemistry on Al-Fe alloys.
AB  - Combinatorial material development was combined with high throughput
      microelectrochemistry to allow an efficient but comprehensive investigation of
      the interface chemistry of Al rich Al-Fe alloys as a function of their chemical
      composition. Composition spread thin films with a linear composition gradient
      were produced by thermal codeposition. A scanning droplet cell was used to
      determine the open circuit potential and to perform successive anodic oxide
      formation with intermittent impedance spectroscopy. The film formation factor,
      the relative permittivity of the oxides and the onset potential of oxide
      formation were determined quantitatively as function of the composition with a
      resolution of 0.5 at.%. An unexpected synergistic effect is found in a very
      narrow composition range between 9 and 12 at.% Fe. This effect, which shifts the
      onset potential by nearly 1 V, is discussed in terms of a local accumulation of
      Fe resulting in a redox stabilisation of space charge layer formation during high
      field oxide growth. The results are supported by composition and depth dependent
      XPS measurements.

PMID- 27878007
TI  - Dc conductivity of consolidated nanoparticles of zinc sulfide.
AB  - Zinc sulfide nanoparticles with average grain sizes ranging from 3 to 12 nm were
      prepared by arrested chemical preparation, followed by suitable thermal
      processing. The size of the grains was determined by x-ray line broadening. Dc
      measurement was performed on compacts of nanoparticles using a Keithley
      electrometer in the temperature range of 313-423 K. The dc conductivity, sigmadc,
      of our samples is much higher than that of ZnS single crystals; sigmadc increases
      with a decrease in the grain size.

PMID- 27878008
TI  - Structural studies of copper sulfide films: effect of ambient atmosphere.
AB  - We examined the structural properties of copper sulfide films as a function of
      the sulfurization time of 70-nm-thick Cu films. Copper sulfide films with various
      phases such as mixed metallic Cu-chalcocite, chalcocite, roxbyite, and covellite
      phases were formed with increasing sulfurization time. To evaluate the structural
      stability of various films, all the films were exposed to the ambient atmosphere
      for the same amount of time. Although the phase structure and stoichiometry of
      the films were maintained at a greater depth, the near-surface region of the
      films was oxidized and covered with overlayers of oxide, hydroxide, and/or
      sulfate species due to the exposure and reaction with the ambient atmosphere. The
      oxygen uptake and its reactivity with the copper sulfide film surfaces were
      enhanced with increasing sulfur content of the films. In addition, the type of
      divalent state of copper formed on the film surfaces depended on the phase
      structure, composition, and stoichiometry of the films.

PMID- 27878009
TI  - Biosynthesis and stabilization of Au and Au-Ag alloy nanoparticles by fungus,
      Fusarium semitectum.
AB  - Crystallized and spherical-shaped Au and Au-Ag alloy nanoparticles have been
      synthesized and stabilized using a fungus, F. semitectum in an aqueous system.
      Aqueous solutions of chloroaurate ions for Au and chloroaurate and Ag+ ions (1 :
      1 ratio) for Au-Ag alloy were treated with an extracellular filtrate of F.
      semitectum biomass for the formation of Au nanoparticles (AuNP) and Au-Ag alloy
      nanoparticles (Au-AgNP). Analysis of the feasibility of the biosynthesized
      nanoparticles and core-shell alloy nanoparticles from fungal strains is
      particularly significant. The resultant colloidal suspensions are highly stable
      for many weeks. The obtained Au and Au-Ag alloy nanoparticles were characterized
      by the surface plasmon resonance (SPR) peaks using a UV-vis spectrophotometer,
      and the structure, morphology and size were determined by Fourier transform
      infrared spectroscopy (FTIR), x-ray diffraction (XRD), and transmission electron
      microscopy (TEM). Possible optoelectronics and medical applications of these
      nanoparticles are envisaged.

PMID- 27878010
TI  - A 3D tomographic EBSD analysis of a CVD diamond thin film.
AB  - We have studied the nucleation and growth processes in a chemical vapor
      deposition (CVD) diamond film using a tomographic electron backscattering
      diffraction method (3D EBSD). The approach is based on the combination of a
      focused ion beam (FIB) unit for serial sectioning in conjunction with high
      resolution EBSD. Individual diamond grains were investigated in 3-dimensions
      particularly with regard to the role of twinning.

PMID- 27878012
TI  - Focus on Superconductivity in Semiconductors.

PMID- 27878011
TI  - Spin drift and spin diffusion currents in semiconductors.
AB  - On the basis of a spin drift-diffusion model, we show how the spin current is
      composed and find that spin drift and spin diffusion contribute additively to the
      spin current, where the spin diffusion current decreases with electric field
      while the spin drift current increases, demonstrating that the extension of the
      spin diffusion length by a strong field does not result in a significant increase
      in spin current in semiconductors owing to the competing effect of the electric
      field on diffusion. We also find that there is a spin drift-diffusion crossover
      field for a process in which the drift and diffusion contribute equally to the
      spin current, which suggests a possible method of identifying whether the process
      for a given electric field is in the spin drift or spin diffusion regime. Spin
      drift-diffusion crossover fields for GaAs are calculated and are found to be
      quite small. We derive the relations between intrinsic spin diffusion length and
      the spin drift-diffusion crossover field of a semiconductor for different
      electron statistical regimes. The findings resulting from this investigation
      might be important for semiconductor spintronics.

PMID- 27878013
TI  - Electrodeposition of nanostructured coatings and their characterization-A review.
AB  - Nanostructured materials have gained importance in recent years due to their
      significantly enhanced properties. In particular, electrochemistry has a special
      role in producing a variety of nanostructured materials. In the current review,
      we discuss the superiority of electrochemical deposition techniques in
      synthesizing various nanomaterials that exhibit improved characteristics compared
      with materials produced by conventional techniques, as well as their
      classification, synthesis routes, properties and applications. The superior
      properties of a nanostructured nickel coating produced by electrochemical
      deposition are outlined. The properties of various nanostructured coating
      materials produced by electrochemical techniques are also described. Finally, the
      importance of nanostructured coatings in industrial applications as well as their
      potential in future technologies is emphasized.

PMID- 27878014
TI  - Selected topics related to the transport and superconductivity in boron-doped
      diamond.
AB  - This contribution deals with a few topics closely related to the
      superconductivity in the heavily boron-doped diamond which are, in our opinion,
      not properly treated in the current literature. Attention is paid especially to
      the classification of metallic and insulating state, selection of pairing
      mechanism, limits of weak coupling approximation and to the influence of
      granularity on the superconducting transition.

PMID- 27878015
TI  - Synthesis and superconducting properties of CaC6.
AB  - Among the superconducting graphite intercalation compounds, CaC6 exhibits the
      highest critical temperature Tc=11.5 K. Bulk samples of CaC6 are obtained by
      immersing highly oriented pyrographite pieces in a well-chosen liquid Li-Ca alloy
      for 10 days at 350  degrees C. The crystal structure of CaC6 belongs to the
      [Formula: see text] space group. In order to study the superconducting properties
      of CaC6, magnetisation was measured as a function of temperature and direction of
      magnetic field applied parallel or perpendicular to the c-axis. Meissner effect
      was evidenced, as well as a type II superconducting behaviour and a small
      anisotropy. In agreement with calculations, experimental results obtained from
      various techniques suggest that a classical electron-phonon mechanism is
      responsible for the superconductivity of CaC6. Application of high pressure
      increases the Tc up to 15.1 K at 8 GPa.

PMID- 27878016
TI  - 11B nuclear magnetic resonance in boron-doped diamond.
AB  - This review summarizes recent results obtained by 11B solid-state nuclear
      magnetic resonance (NMR) on boron-doped diamond, grown by the high-pressure high
      temperature (HPHT) or chemical vapor deposition techniques. Simple single-pulse
      experiments as well as advanced two-dimensional NMR experiments were applied to
      the boron sites in diamond. It is shown that magic-angle spinning at magnetic
      fields above 10 T is suitable for observation of high-resolution 11B spectra of
      boron-doped diamond. For boron-doped HPHT diamonds, the existence of the excess
      boron that does not contribute to electrical conductivity was confirmed and its
      11B NMR signal was characterized. The point-defect structures (B+H complexes and 
      B-B-/-B-C-B- clusters), postulated previously for the excess boron, were
      discarded and graphite-like structures were assigned instead.

PMID- 27878017
TI  - Impurity band Mott insulators: a new route to high Tc superconductivity.
AB  - Last century witnessed the birth of semiconductor electronics and nanotechnology.
      The physics behind these revolutionary developments is certain quantum mechanical
      behaviour of 'impurity state electrons' in crystalline 'band insulators', such as
      Si, Ge, GaAs and GaN, arising from intentionally added (doped) impurities. The
      present article proposes that certain collective quantum behaviour of these
      impurity state electrons, arising from Coulomb repulsions, could lead to
      superconductivity in a parent band insulator, in a way not suspected before.
      Impurity band resonating valence bond theory of superconductivity in boron doped
      diamond, recently proposed by us, suggests possibility of superconductivity
      emerging from impurity band Mott insulators. We use certain key ideas and
      insights from the field of high-temperature superconductivity in cuprates and
      organics. Our suggestion also offers new possibilities in the field of
      semiconductor electronics and nanotechnology. The current level of sophistication
      in solid state technology and combinatorial materials science is very well
      capable of realizing our proposal and discover new superconductors.

PMID- 27878018
TI  - Superconductivity in compensated and uncompensated semiconductors.
AB  - We investigate the localization and superconductivity in heavily doped
      semiconductors. The crossover from the superconductivity in the host band to that
      in the impurity band is described on the basis of the disordered three
      dimensional attractive Hubbard model for binary alloys. The microscopic
      inhomogeneity and the thermal superconducting fluctuation are taken into account
      using the self-consistent 1-loop order theory. The superconductor-insulator
      transition accompanies the crossover from the host band to the impurity band. We
      point out an enhancement of the critical temperature Tc around the crossover.
      Further localization of electron wave functions leads to the localization of
      Cooper pairs and induces the pseudogap. We find that both the doping compensation
      by additional donors and the carrier increase by additional acceptors suppress
      the superconductivity. A theoretical interpretation is proposed for the
      superconductivity in the boron-doped diamond, SiC, and Si.

PMID- 27878019
TI  - Unconventional pairing in doped band insulators on a honeycomb lattice: the role
      of the disconnected Fermi surface and a possible application to superconducting
      beta-MNCl (M=Hf, Zr).
AB  - We investigate the possibility of realizing unconventional superconductivity in
      doped band insulators on the square and honeycomb lattices. The latter lattice is
      found to be a good candidate due to the disconnectivity of the Fermi surface. We
      propose applying the theory to the superconductivity in doped layered nitride
      beta-MNCl (M= Hf, Zr). Finally, we compare two groups of superconductors with
      disconnected Fermi surface, beta-MNCl and the iron pnictides, which have high
      critical temperature Tc, despite some faults against superconductivity are
      present.

PMID- 27878020
TI  - Electronic structures and three-dimensional effects of boron-doped carbon
      nanotubes.
AB  - We study boron-doped carbon nanotubes by first-principles methods based on the
      density functional theory. To discuss the possibility of superconductivity, we
      calculate the electronic band structure and the density of states (DOS) of boron
      doped (10,0) nanotubes by changing the boron density. It is found that the Fermi
      level density of states D(?F) increases upon lowering the boron density. This can
      be understood in terms of the rigid band picture where the one-dimensional van
      Hove singularity lies at the edge of the valence band in the DOS of the pristine
      nanotube. The effect of three-dimensionality is also considered by performing the
      calculations for bundled (10,0) nanotubes and boron-doped double-walled carbon
      nanotubes (10,0)@(19,0). From the calculation of the bundled nanotubes, it is
      found that interwall dispersion is sufficiently large to broaden the peaks of the
      van Hove singularity in the DOS. Thus, to achieve the high D(?F) using the bundle
      of nanotubes with single chirality, we should take into account the distance from
      each nanotube. In the case of double-walled carbon nanotubes, we find that the
      holes introduced to the inner tube by boron doping spread also on the outer tube,
      while the band structure of each tube remains almost unchanged.

PMID- 27878021
TI  - Superconductivity in carrier-doped silicon carbide.
AB  - We report growth and characterization of heavily boron-doped 3C-SiC and 6H-SiC
      and Al-doped 3C-SiC. Both 3C-SiC:B and 6H-SiC:B reveal type-I superconductivity
      with a critical temperature Tc=1.5 K. On the other hand, Al-doped 3C-SiC (3C
      SiC:Al) shows type-II superconductivity with Tc=1.4 K. Both SiC:Al and SiC:B
      exhibit zero resistivity and diamagnetic susceptibility below Tc with effective
      hole-carrier concentration n higher than 1020 cm-3. We interpret the different
      superconducting behavior in carrier-doped p-type semiconductors SiC:Al, SiC:B,
      Si:B and C:B in terms of the different ionization energies of their acceptors.

PMID- 27878022
TI  - Superconductivity in heavily boron-doped silicon carbide.
AB  - The discoveries of superconductivity in heavily boron-doped diamond in 2004 and
      silicon in 2006 have renewed the interest in the superconducting state of
      semiconductors. Charge-carrier doping of wide-gap semiconductors leads to a
      metallic phase from which upon further doping superconductivity can emerge.
      Recently, we discovered superconductivity in a closely related system: heavily
      boron-doped silicon carbide. The sample used for that study consisted of cubic
      and hexagonal SiC phase fractions and hence this led to the question which of
      them participated in the superconductivity. Here we studied a hexagonal SiC
      sample, free from cubic SiC phase by means of x-ray diffraction, resistivity, and
      ac susceptibility.

PMID- 27878023
TI  - Two-gap superconductivity in R2Fe3Si5 (R=Lu, Sc) and Sc5Ir4Si10.
AB  - R2Fe3Si5 (R= Sc, Y, Lu) contains nonmagnetic iron and has a relatively high
      superconducting transition temperature Tc among iron-containing superconductors.
      An anomalous temperature dependence of specific heat C(T) has been reported for
      polycrystalline samples down to 1 K. We have grown R2Fe3Si5 single crystals,
      confirmed the anomalous C(T) dependence, and found a second drop in specific heat
      below 1 K. In Lu2Fe3Si5, we can reproduce C(T) below Tc, assuming two distinct
      energy gaps 2Delta 1/kBTc = 4.4 and 2Delta 2/kBTc = 1.1, with nearly equal
      weights, indicating that Lu2Fe3Si5 is a two-gap superconductor similar to MgB2.
      Hall coefficient measurements and band structure calculation also support the
      multiband contributions to the normal-state properties. The specific heat in the
      Sc2Fe3Si5 single crystals also shows the two-gap feature. R5Ir4Si10 (R = Sc, rare
      earth) is also a superconductor where competition between superconductivity and
      the charge-density wave is known for rare earths but not for Sc. We have
      performed detailed specific heat measurements on Sc5Ir4Si10 single crystals and
      found that C(T) deviates slightly from the behavior expected for weak-coupling
      superconductors. C(T) for these superconductors can also be reproduced well by
      assuming two superconducting gaps.

PMID- 27878024
TI  - Soft x-ray photoelectron spectroscopy study of type-I clathrates.
AB  - Extensive soft x-ray photoelectron spectroscopy studies are performed on Ba8 Ga16
      Ge30 (BGG) and Sr8Ga16Ge30 (SGG) single crystals ranging from Fermi to core
      levels, at a high-energy facility. Valence band x-ray photoelectron spectroscopy
      (XPS) experiments with theoretical calculations revealed that the valence band is
      mainly constructed by the Ge/Ga 4s and 4p wave functions with little contribution
      of the Ba/Sr atomic orbitals. Surprisingly, unexpected features evidencing the
      different shift for the 2a- and 6d- sites between Ba 4d and Sr 3d are observed.
      The detailed analyses including theoretical support by first-principles band
      structure calculations lead to the conclusion that the component distributions of
      the larger tetrakaidecahedral cage are different depending on the endohedral
      atoms, which contrasts with the past consensus that BGG and SGG have the same
      framework structure. This may give thorough reconsiderations on earlier
      interpretations of experimental data.

PMID- 27878026
TI  - Synthesis of an orthorhombic high pressure boron phase.
AB  - The densest boron phase (2.52 g cm-3) was produced as a result of the synthesis
      under pressures above 9 GPa and temperatures up to ~1800  degrees C. The x-ray
      powder diffraction pattern and the Raman spectra of the new material do not
      correspond to those of any known boron phases. A new high-pressure high
      temperature boron phase was defined to have an orthorhombic symmetry (Pnnm (No.
      58)) and 28 atoms per unit cell.

PMID- 27878025
TI  - Superconductivity in transparent zinc-doped In2O3 films having low carrier
      density.
AB  - Thin polycrystalline zinc-doped indium oxide (In2O3-ZnO) films were prepared by
      post-annealing amorphous films with various weight concentrations x of ZnO in the
      range 0?x ?0.06. We have studied the dependences of the resistivity rho and Hall
      coefficient on temperature T and magnetic field H in the range 0.5?T ?300 K, H?6
      Tfor 350 nm films annealed in air. Films with 0?x?0.03 show the superconducting
      resistive transition. The transition temperature Tc is below 3.3 K and the
      carrier density n is about 1025-1026 m-3. The annealed In2O3-ZnO films were
      examined by transmission electron microscopy and x-ray diffraction analysis
      revealing that the crystallinity of the films depends on the annealing time. We
      studied the upper critical magnetic field Hc2 (T) for the film with x = 0.01.
      From the slope of dHc2 /dT, we obtain the coherence length xi (0) ~ 10 nm at T =
      0 K and a coefficient of electronic heat capacity that is small compared with
      those of other oxide materials.

PMID- 27878027
TI  - Structure and superconductivity of isotope-enriched boron-doped diamond.
AB  - Superconducting boron-doped diamond samples were synthesized with isotopes of
      10B, 11B, 13C and 12C. We claim the presence of a carbon isotope effect on the
      superconducting transition temperature, which supports the 'diamond-carbon'
      related nature of superconductivity and the importance of the electron-phonon
      interaction as the mechanism of superconductivity in diamond. Isotope
      substitution permits us to relate almost all bands in the Raman spectra of
      heavily boron-doped diamond to the vibrations of carbon atoms. The 500 cm-1 Raman
      band shifts with either carbon or boron isotope substitution and may be
      associated with vibrations of paired or clustered boron. The absence of a
      superconducting transition (down to 1.6 K) in diamonds synthesized in the Co-C-B
      system at 1900 K correlates with the small boron concentration deduced from
      lattice parameters.

PMID- 27878028
TI  - Electronic structure of boron-doped diamond with B-H complex and B pair.
AB  - The electronic structure of boron-hydrogen complex and boron pair in diamond are
      studied by first-principles density-functional calculations with supercell
      models. The electronic structure calculated for the B-H complexes with C2v or C3v
      symmetry and the nearest-neighbor B pair is used to interpret recent experimental
      results such as B 1s x-ray photoemission spectroscopy, 11B nuclear quadruple
      resonance and B K-edge x-ray absorption spectroscopy, which cannot be explained
      solely by the isolated substitutional boron.

PMID- 27878029
TI  - Shift in room-temperature photoluminescence of low-fluence Si+-implanted SiO2
      films subjected to rapid thermal annealing.
AB  - We experimentally demonstrate the effect of the rapid thermal annealing (RTA) in
      nitrogen flow on photoluminescence (PL) of SiO2 films implanted by different
      doses of Si+ ions. Room-temperature PL from 400-nm-thick SiO2 films implanted to
      a dose of 3*1016 cm-2 shifted from 2.1 to 1.7 eV upon increasing RTA temperature
      (950-1150  degrees C) and duration (5-20 s). The reported approach of implanting
      silicon into SiO2 films followed by RTA may be effective for tuning Si-based
      photonic devices.

PMID- 27878030
TI  - Corrosion behavior of metals and alloys in marine-industrial environment.
AB  - This work deals with atmospheric corrosion to assess the degrading effects of air
      pollutants on ferrous and non-ferrous metals and alloys, which are mostly used as
      engineering materials. An exposure study was conducted in the Tuticorin port area
      located on the east coast of South India, in the Gulf of Mannar with Sri Lanka to
      the southeast. Common engineering materials, namely mild steel, galvanized iron,
      Zn, Al, Cu and Cu-Zn alloys (Cu-27Zn, Cu-30Zn and Cu-37Zn), were used in the
      investigation. The site was chosen where the metals are exposed to marine and
      industrial atmospheres. Seasonal 1 to 12 month corrosion losses of these metals
      and alloys were determined by a weight loss method. The weight losses showed
      strong corrosion of mild steel, galvanized iron, Cu and Zn and minor effect on Al
      and Cu-Zn alloys. Linear regression analysis was conducted to study the mechanism
      of corrosion. The composition of corrosion products formed on the metal surfaces
      was identified by x-ray diffraction and Fourier transform infrared spectroscopy.

PMID- 27878031
TI  - Positive segregation as a function of buoyancy force during steel ingot
      solidification.
AB  - We analyze theoretically and experimentally solute redistribution in the
      dendritic solidification process and positive segregation during solidification
      of steel ingots. Positive segregation is mainly caused by liquid flow in the
      mushy zone. Changes in the liquid steel velocity are caused by the temperature
      gradient and by the increase in the solid fraction during solidification. The
      effects of buoyancy and of the change in the solid fraction on segregation
      intensity are analyzed. The relationships between the density change, liquid
      fraction and the steel composition are considered. Such elements as W, Ni, Mo and
      Cr decrease the effect of the density variations, i.e. they show smaller tendency
      to segregate. Based on the modeling and experimental results, coefficients are
      provided controlling the effects of chemical composition, secondary dendrite arm
      spacing and the solid fraction.

PMID- 27878032
TI  - Rate-dependent serrated flow and plastic deformation in Ti45Zr16Be20Cu10Ni9 bulk
      amorphous alloy during nanoindentation.
AB  - The plastic deformation of Ti45Zr16Be20Cu10Ni9 bulk metallic glass has been
      investigated by nanoindentation performed with loads ranging from 10 to 200 mN in
      a wide range of loading rates. The plastic flow in the alloy exhibited
      conspicuous serrations at low loading rates. The serrations, however, became less
      prominent as the rate of indentation increased. Atomic force microscopy showed a
      significant pile-up of materials around the indents, indicating that a highly
      localized plastic deformation occurred under nanoindentation. The possible
      mechanism governing the plastic deformation in bulk metallic glass specimens is
      tentatively discussed in terms of strain-induced free volume.

PMID- 27878033
TI  - Reinforcement of dynamically vulcanized EPDM/PP elastomers using organoclay
      fillers.
AB  - Dynamically vulcanized EPDM/PP (ethylene-propylene-diene/polypropylene)
      elastomers reinforced with various amounts of organoclay were prepared using
      octylphenol-formaldehyde resin and stannous chloride dehydrate as vulcanizing
      agents. The effects of organoclay on vulcanization characteristics, rheological
      behavior, morphology, thermal stability and thermomechanical properties were
      studied. Experimental results showed that organoclay affected neither the
      vulcanization process nor the degree of vulcanization chemically. X-ray analysis
      revealed that these organoclay-filled thermoplastic vulcanizates (TPVs) were
      intercalated. With respect to the mechanical properties, organoclay increased
      both the strength and degree of elongation of TPVs. The morphological observation
      of fractured surfaces suggested that organoclay acted as a nucleating agent in
      TPVs, improving their mechanical properties. However, adding organoclay reduced
      the thermal stability of TPVs by decomposing the swelling agents in the
      organoclay.

PMID- 27878034
TI  - Application of dynamic impedance spectroscopy to atomic force microscopy.
AB  - Atomic force microscopy (AFM) is a universal imaging technique, while impedance
      spectroscopy is a fundamental method of determining the electrical properties of
      materials. It is useful to combine those techniques to obtain the spatial
      distribution of an impedance vector. This paper proposes a new combining approach
      utilizing multifrequency scanning and simultaneous AFM scanning of an
      investigated surface.

PMID- 27878035
TI  - Preparation and characterization of self-cleaning stable superhydrophobic linear
      low-density polyethylene.
AB  - Porous superhydrophobic linear low-density polyethylene (LLDPE) surface was
      prepared by a simple method. Its water contact angle and sliding angle were 153+/
      2 degrees  and 10 degrees , respectively. After contamination, 99% of the
      contaminant particles were removed from the superhydrophobic LLDPE surface using
      artificial rain. The superhydrophobic LLDPE surface showed high stability in the
      pH range from 2 to 13. When LLDPE samples were stored in ambient environment for
      one month, their water contact angle and sliding angle remained constant. Their
      superhydrophobic property was also maintained after annealing in the temperature
      range 10-90  degrees C.

PMID- 27878036
TI  - Microwave-assisted synthesis of WS2 nanowires through tetrathiotungstate
      precursors.
AB  - Tungsten disulfide (WS2) nanowires have been synthesized through a microwave
      assisted chemical route that uses tungstic acid, elemental sulfur and
      monoethanolamine as starting reagents for obtaining a precursor solution of
      tetrathiotungstate ions. Acidification of the precursor solution yields amorphous
      precipitates, which lead to the formation of nanowires of WS2 with thickness of
      about 5-10 nm when heated at 750  degrees C under argon atmosphere for 1.5 h.
      Phase and the microstructure of the prepared powders have been investigated
      through x-ray powder diffraction and high-resolution transmission electron
      microscopy, respectively. Optical absorption of the WS2 powders reveals a red
      shift of the exciton bands compared to bulk WS2.

PMID- 27878037
TI  - Effect of zinc phosphate chemical conversion coating on corrosion behaviour of
      mild steel in alkaline medium: protection of rebars in reinforced concrete.
AB  - We outline the ability of zinc phosphate coatings, obtained by chemical
      conversion, to protect mild steel rebars against localized corrosion, generated
      by chloride ions in alkaline media. The corrosion resistance of coated steel, in
      comparison with uncoated rebars and coated and uncoated steel rebars embedded in
      mortar, were evaluated by open-circuit potential, potentiodynamic polarization,
      cronoamperometry and electrochemical impedance spectroscopy. The coated surfaces
      were characterized by x-ray diffraction and scanning electron microscopy. First,
      coated mild steel rebars were studied in an alkaline solution with and without
      chloride simulating a concrete pore solution. The results showed that the slow
      dissolution of the coating generates hydroxyapatite Ca10(PO4)6(OH)2. After a long
      immersion, the coating became dense and provided an effective corrosion
      resistance compared with the mild steel rebar. Secondly, the coated and uncoated
      steel rebars embedded in mortar and immersed in chloride solution showed no
      corrosion or deterioration of the coated steel. Corrosion rate is considerably
      lowered by this phosphate coating.

PMID- 27878038
TI  - The business of urology.

PMID- 27878039
TI  - Canadian Urological Association annual meeting: Built on a foundation of
      volunteerism.

PMID- 27878040
TI  - Effect of contrast media on urinary cytopathology specimens.
AB  - INTRODUCTION: Urological dogma dictates that washings collected from the urinary
      tract for cytological assessment must be performed without interference from
      contrast agents that may alter cellular integrity and diagnostic interpretation.
      In practice, the initial contrast used to outline the upper tracts is commonly
      discarded with subsequent saline washings sent for cytology. We hypothesize that
      contrast washings do not affect the morphology of urothelial carcinoma cells or
      the integrity of cytology interpretation. METHODS: Samples obtained from (1)
      human bladder cell lines; (2) urine from a human xenograft bladder cancer model
      using UC-3 cells; and (3) patients with urothelial carcinoma were subjected to
      various experimental solutions (water, saline, urine, and dilutions of contrast
      media) for different exposure times. After exposure to various different
      solutions, samples underwent cytological analysis to assess morphologic and
      degenerative changes. RESULTS: No cytological differences were seen when cells
      were exposed to ionic, hyperosmolar, or non-ionic low-osmolar contrast agents for
      any exposures up to five minutes. Cells exposed to mixtures of contrast agents
      and urine also demonstrated no evidence of degenerative change. Cells exposed to
      water for greater than one minute demonstrated significant hydropic degeneration
      impacting cytological interpretation. At 40 minutes or later, all reagents caused
      severe degeneration when evaluating urine samples from the mouse bladder cancer
      model and from patients undergoing urothelial carcinoma. CONCLUSIONS: Commonly
      used contrast agents have no effect on urinary cytology up to five minutes.
      Contrast washings of the urinary tract should not be discarded and can be sent
      for cytological diagnosis if fixed within this time period.

PMID- 27878042
TI  - Advocating lifestyle modification to reduce risk of stone recurrence.

PMID- 27878041
TI  - A prospective evaluation of obesometric parameters associated with renal stone
      recurrence.
AB  - INTRODUCTION: Our aim was to evaluate whether obesometric serum hormones and body
      fat distribution are associated with renal stone recurrence. METHODS: We
      conducted a prospective cohort study of participants undergoing renal stone (RS)
      intervention at a single institution from November 2009-June 2010 and followed
      them for a median 62 months. Obesometric parameters were measured at baseline,
      including body mass index (BMI), fasting serum leptin and adiponectin, and
      proportion of visceral adipose tissue (%VAT) averaged from three fixed axial
      computed tomography (CT) slices. The primary study outcome was stone recurrence.
      RESULTS: A total of 110 participants were enrolled. Elevated %VAT was associated
      RS recurrence; participants with %VAT in the highest quartile had a five-year
      stone-free rate of 47.1% compared to 72.2% among other participants (p=0.004).
      Adjusting for gender, elevated %VAT was independently predictive of renal stone
      recurrence among initial stone formers (n=74; hazard ratio [HR] 4.53, 95%
      confidence interval [CI] 1.08-19.02), but not among recurrent stone formers
      (n=19; HR 0.51, 95% CI 0.054-4.72). Other obesometric factors, including leptin,
      adiponectin, and BMI, were not significantly predictive of recurrence.
      CONCLUSIONS: We report a novel association between an elevated %VAT and stone
      recurrence. These findings may inform patient counselling and followup regimens.
      The metabolic basis for these findings requires further investigation.

PMID- 27878043
TI  - Exploring the business of urology: Leadership.

PMID- 27878044
TI  - A comparative study of radical prostatectomy and permanent seed brachytherapy for
      low- and intermediate-risk prostate cancer.
AB  - INTRODUCTION: We sought to compare the outcomes between radical prostatectomy
      (RP) and permanent seed prostate brachytherapy (PB) in patients with low- and low
      intermediate-risk prostate cancer from a single tertiary care centre. METHODS:
      Patients were selected from our institute's internal database based on
      preoperative selection criteria from the National Comprehensive Cancer Network
      (NCCN) guidelines (2015) for low- and intermediate-risk patients. No patient had
      received any neo-adjuvant androgen-deprivation therapy. The endpoint was
      biochemical recurrence (BCR) or any salvage treatment for both RP and PB at 48 +/
      4 months after treatment. The biochemical relapse threshold was set at prostate
      specific antigen (PSA) >=0.5 ng/mL for PB and two PSA values of >=0.2 ng/mL for
      RP. Patients from both treatment groups were compared using non-parametric tests.
      A binary logistic regression analysis was performed to determine an association
      of treatment and pretreatment factors with a BCR at 48 months. RESULTS: A total
      of 575 patients were included in this study; 254 were treated with RP and 321
      with PB. BCR was not different between both groups (p=0.84, Chi-square test), and
      occurred in 21.2% of patients treated with RP and in 20.6% with PB. Based on
      univariate and multivariate logistic regression analyses, younger age, higher
      percentage of positive biopsies, and initial PSA were predictive of BCR.
      Treatment modality was not predictive in either univariate (odds ratio [OR] 0.96,
      95% confidence interval [CI] 0.64-1.44; p=0.84) or multivariate (OR 1.43, 95% CI
      0.89-2.30; p=0.14) analyses. CONCLUSIONS: Using closely related cutoff values for
      BCR, both RP and PB did not have significantly different outcomes at four years
      post-treatment. A longer followup may be necessary to detect a difference between
      treatments.

PMID- 27878045
TI  - Current prostate cancer treatment: Not what but when?

PMID- 27878046
TI  - Back-to-back comparison of mini-open vs. laparoscopic technique for living kidney
      donation.
AB  - INTRODUCTION: Laparoscopic living donor nephrectomy is the standard of care at
      high-volume renal transplant centres, with benefits over the open approach well
      documented in the literature. Herein, we present a retrospective analysis of our
      single-institution donor nephrectomy series comparing the mini-open donor
      nephrectomy (mini-ODN) to the laparoscopic donor nephrectomy (LDN) with regards
      to operative, donor, and recipient outcomes. METHODS: From 2007-2011, there were
      89 cases of mini-ODN, at which point our centre transitioned to LDN; 94 cases
      were performed from 2011-2014. In total, 366 patients were reviewed, including
      donor and recipient pairs. Donor and recipient demographics, intraoperative data,
      postoperative donor recovery, recipient graft outcomes, and financial cost were
      assessed comparing the surgical approaches. RESULTS: We demonstrate a reduced
      estimated blood loss (347.83 vs. 90.3 cc), lower intraoperative complication rate
      (4 vs. 11) and shorter length of hospital stay (2.4 vs. 3.3 days) for patients in
      the LDN group. Operative time was significantly longer for the LDN group (108.4
      vs. 165.9 minutes), although this did not translate to a longer warm ischemia
      time (mean 2.0 minutes for each group). The rate of delayed graft function and
      recipient 12-month creatinine were comparable for ODN and LND. Overall cost of
      LDN was $684 higher for an uncomplicated admission. CONCLUSIONS: Despite a longer
      surgical time and higher upfront cost, our study supports that LDN yields several
      advantages over the mini-ODN, with a lower estimated blood loss, fewer
      intraoperative complications, and shorter length of hospital stay, all while
      maintaining excellent renal allograft outcomes.

PMID- 27878047
TI  - Optimal surgical strategies in living kidney donation.

PMID- 27878048
TI  - Validation of a prediction model for avoiding post-chemotherapy retroperitoneal
      lymphadenectomy in patients with metastatic nonseminomatous germ cell cancer.
AB  - INTRODUCTION: Post-chemotherapy residual masses (PCRMs) may contain persistent
      cancer or teratoma in more than 50% of patients with metastatic non-seminomatous
      germ cell tumours (mNSGCTs). Retroperitoneal lymph node dissection (RPLND) is
      curative, but controversy exists about selection criteria for surgery. A
      validated prediction model by Vergouwe et al (2007) based on over 1000 patients
      was evaluated at our centre. METHODS: mNSGCT patients treated with RPLND for
      PCRMs were identified from an electronic database. Typographical errors in the
      model were identified and corrected using their 2003 publication, but retaining
      the 2007 coefficients. Six clinical variables were included in the model and the
      calculated probability of benign tissue was compared with pathology. "Benign
      tissue only" was considered a positive test outcome in patients with a predicted
      probability of "benign tissue only" greater than 70%. RESULTS: Fifty-two (52)
      mNSGCT patients between 1980 and 2014 were evaluable. Median age was 32 years
      (range 17-52) and International Germ Cell Consensus Classification (IGCCC)
      prognostic stages were: good 46.2%, intermediate 32.7%, and poor 21.2%. Most
      patients received bleomycin/etoposide/cisplatin (BEP) chemotherapy and full
      bilateral RPLND. Pathology showed residual cancer or teratoma in 31 patients
      (59.6%) and benign findings in 21 patients (40.6%). Positive and negative
      predictive values and accuracy were 100%, 69%, and 73%, respectively.
      CONCLUSIONS: "Benign tissue only" was found in 100% of patients in whom this was
      predicted using our pre-determined criteria. This study involved a limited number
      of patients, but confirms the potential value of the Vergouwe et al model.
      Routine use of this prediction model in clinical practice should be tested for
      mNSGCT patients with PCRMs.

PMID- 27878049
TI  - Prostate volume estimations using magnetic resonance imaging and transrectal
      ultrasound compared to radical prostatectomy specimens.
AB  - INTRODUCTION: We sought to evaluate the accuracy of prostate volume estimates in
      patients who received both a preoperative transrectal ultrasound (TRUS) and
      magnetic resonance imaging (MRI) in relation to the referent pathological
      specimen post-radical prostatectomy. METHODS: Patients receiving both TRUS and
      MRI prior to radical prostatectomy at one academic institution were
      retrospectively analyzed. TRUS and MRI volumes were estimated using the prolate
      ellipsoid formula. TRUS volumes were collected from sonography reports. MRI
      volumes were estimated by two blinded raters and the mean of the two was used for
      analyses. Pathological volume was calculated using a standard fluid displacement
      method. RESULTS: Three hundred and eighteen (318) patients were included in the
      analysis. MRI was slightly more accurate than TRUS based on interclass
      correlation (0.83 vs. 0.74) and absolute risk bias (higher proportion of
      estimates within 5, 10, and 20 cc of pathological volume). For TRUS, 87 of 298
      (29.2%) prostates without median lobes differed by >10 cc of specimen volume and
      22 of 298 (7.4%) differed by >20 cc. For MRI, 68 of 298 (22.8%) prostates without
      median lobes differed by >10 cc of specimen volume, while only 4 of 298 (1.3%)
      differed by >20 cc. CONCLUSIONS: MRI and TRUS prostate volume estimates are
      consistent with pathological volumes along the prostate size spectrum. MRI
      demonstrated better correlation with prostatectomy specimen volume in most
      patients and may be better suited in cases where TRUS and MRI estimates are
      disparate. Validation of these findings with prospective, standardized ultrasound
      techniques would be helpful.

PMID- 27878050
TI  - Suboptimal use of pelvic lymph node dissection: Differences in guideline
      adherence between robot-assisted and open radical prostatectomy.
AB  - INTRODUCTION: Our aim was to assess adherence to National Comprehensive Cancer
      Network (NCCN) and American Urological Association (AUA) guidelines for pelvic
      lymph node dissection (PLND) at the time of either robot-assisted (RARP) or open
      radical prostatectomy (ORP). METHODS: We relied on the Surveillance,
      Epidemiology, and End Results-Medicare linked database and focused on localized
      prostate cancer (PCa) patients who were treated with either RARP or ORP between
      October 2008 and December 2009. Categorical and multivariable logistic regression
      analyses targeted two endpoints: 1) probability of guideline-recommended PLND;
      and 2) probability of no PLND, when not guideline-recommended. RESULTS: Among
      5268 PCa patients, adherence to NCCN PLND guideline was 56.9% during RARP and
      76.5% during ORP (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.3-0.6). AUA
      PLND guideline adherence was 68.1% during RARP and 82.4% during ORP (OR 0.7, 95%
      CI 0.5-0.9). When PLND was not recommended, it was more frequently performed
      during ORP according to either NCCN (OR 3.7, 95% CI 3.5-3.9) or AUA (OR 2.7, 95%
      CI 2.6-2.8). According to the NCCN guideline, at recommended PLND in ORP
      patients, 6.3% harboured lymph node invasion (LNI) (number needed to treat [NNT]
      16) vs. 3.2% at RARP (NNT 31). According to the AUA guideline, at recommended
      PLND in ORP patients, 12.3% harboured LNI (NNT 8) vs. 5.1% RARP (NNT 19).
      CONCLUSIONS: Adherence to NCCN and AUA PLND guidelines was lower during RARP than
      during ORP when PLND was recommended. The rate of non-recommended PLND was also
      higher during ORP than during RARP. Technical considerations may be at play.

PMID- 27878051
TI  - Anticholinergics for overactive bladder: Temporal trends in prescription and
      treatment persistence.
AB  - INTRODUCTION: We sought to understand the contemporary pharmacologic management
      of overactive bladder (OAB) in a single-payer system. We examined temporal trends
      in the use of anticholinergic medications and assessed whether the likelihood of
      patients changing their anticholinergic therapy was predicted by their current
      therapy. METHODS: We conducted a retrospective, population-based analysis of
      prescription records from the PharmaNet database in BC, Canada. We identified
      patients treated with one or more anticholinergic prescriptions between 2001 and
      2009. We characterized temporal trends in the use of anticholinergic medications.
      We used generalized estimating equations with a logit wing to assess the
      relationship between the type of anticholinergic medication and the change in
      prescription. RESULTS: The 114 325 included patients filled 1 140 296 anti
      cholinergic prescriptions. The number of prescriptions each year increased over
      the study, both in aggregate and for each individual medication. While oxybutynin
      was the most commonly prescribed medication (68% of all prescriptions), the
      proportion of newer anticholinergics (solifenacin, darifenacin, and trospium)
      prescribed increased over time (p<0.0001). Patients taking tolterodine (odds
      ratio [OR] 1.03; p=0.01) and darifenacin (OR 1.12; p=0.0006) were significantly
      more likely to change their prescription than those taking oxybutynin. There was
      no association seen for patients taking solifenacin (p=0.6) and trospium (p=0.9).
      CONCLUSIONS: There are an increasing number of anticholinergic prescriptions
      being filled annually. Patients taking newer anticholinergics are at least as
      likely to change therapy as those taking oxybutynin. The reimbursement
      environment in BC likely affects these results. Restrictions in the available
      data limit assessment of other relevant predictors.

PMID- 27878052
TI  - Missing the mark: Current practices in teaching the male urogenital examination
      to Canadian undergraduate medical students.
AB  - INTRODUCTION: The urogenital physical examination is an important aspect of
      patient encounters in various clinical settings. Introductory clinical skills
      sessions are intended to provide support and alleviate students' anxiety when
      learning this sensitive exam. The techniques each Canadian medical school uses to
      guide their students through the initial urogenital examination has not been
      previously reported. METHODS: This study surveyed pre-clerkship clinical skills
      program directors at the main campus of English-speaking Canadian medical schools
      regarding the curriculum they use to teach the urogenital examination. RESULTS: A
      response rate of 100% was achieved, providing information on resources and
      faculty available to students, as well as the manner in which students were
      evaluated. Surprisingly, over one-third of the Canadian medical schools surveyed
      failed to provide a setting in which students perform a urogenital examination on
      a patient in their pre-clinical years. Additionally, there was no formal
      evaluation of this skill set reported by almost 50% of Canadian medical schools
      prior to clinical training years. CONCLUSIONS: To ensure medical students are
      confident and accurate in performing a urogenital examination, it is vital they
      be provided the proper resources, teaching, and training. As we progress towards
      a competency-based curriculum, it is essential that increased focus be placed on
      patient encounters in undergraduate training. Further research to quantify
      students' exposure to the urogenital examination during clinical years would be
      of interest. Without this commitment by Canadian medical schools, we are doing a
      disservice not only to the medical students, but also to our patient population.

PMID- 27878053
TI  - Treatment strategies for large impacted upper ureteral stones.

PMID- 27878055
TI  - CUA-AUA International Fellows Program: San Diego 2016.

PMID- 27878054
TI  - CUA guideline: Vasectomy.

PMID- 27878056
TI  - CUA-AUA International Fellows Program: San Diego 2016.

PMID- 27878057
TI  - Correction in figure.
AB  - [This corrects the article on p. 99 in vol. 9, PMID: 26085866.].

PMID- 27878059
TI  - Assessment of Online Patient Education Materials from Major Dermatologic
      Associations.
AB  - Objective: Patients increasingly use the internet to find medical information
      regarding their conditions and treatments. Physicians often supplement visits
      with written education materials. Online patient education materials from major
      dermatologic associations should be written at appropriate reading levels to
      optimize utility for patients. The purpose of this study is to assess online
      patient education materials from major dermatologic associations and determine if
      they are written at the fourth to sixth grade level recommended by the American
      Medical Association and National Institutes of Health. Design: This is a
      descriptive and correlational design. Setting: Academic institution.
      Participants/measurements: Patient education materials from eight major
      dermatology websites were downloaded and assessed using 10 readability scales. A
      one-way analysis of variance and Tukey's Honestly Statistically Different post
      hoc analysis were performed to determine the difference in readability levels
      between websites. Results: Two hundred and sixty patient education materials were
      assessed. Collectively, patient education materials were written at a mean grade
      level of 11.13, with 65.8 percent of articles written above a tenth grade level
      and no articles written at the American Medical Association/National Institutes
      of Health recommended grade levels. Analysis of variance demonstrated a
      significant difference between websites for each reading scale (p<0.001), which
      was confirmed with Tukey's Honestly Statistically Different post hoc analysis.
      Conclusion: Online patient education materials from major dermatologic
      association websites are written well above recommended reading levels.
      Associations should consider revising patient education materials to allow more
      effective patient comprehension. (J ClinAesthet Dermatol. 2016;9(9):23-28.).

PMID- 27878058
TI  - Patient Factors and Their Association with Nonmelanoma Skin Cancer Morbidity and
      the Performance of Self-skin Exams: A Cross-Sectional Study.
AB  - Objective: Mohs micrographic surgery is widely utilized for the treatment of
      nonmelanoma skin cancers with the advantage of tissue sparing and higher cure
      rate. The preoperative tumor size and post-Mohs micrographic surgery defect size
      are useful surrogate measures of nonmelanoma skin cancer morbidity. The authors
      sought to evaluate whether gender, Hispanic ethnicity, socioeconomic status, sun
      safe practices and self-skin exams affected tumor size and Mohs micrographic
      surgery defect size. They also investigated factors associated with self-skin
      exams. Design: A cross-sectional survey-based study. Setting: Two dermatologic
      surgery clinics-one academic-associated and the other private. Participants:
      Patients receiving Mohs surgery for nonmelanoma skin cancers. Measurements: Tumor
      size and Mohs defect size and their relationship to patient factors ascertained
      from a survey, as well as the number of patients performing self-skin exams. The
      authors used t-tests and analysis of variance to compare tumor and defect sizes
      for each patient factor. Chi-squared tests were used to determine the factors
      associated with self-skin exams performance. Results: Lower education was
      associated with greater head and face tumor area (95mm2 vs. 41mm2, P=0.019), but
      not Mohs micrographic surgery defect size. Other studied patient factors were not
      associated with an increased morbidity. Hispanics performed self-skin exams at a
      lower rate than non-Hispanics (27% vs. 46%, p=0.03). Conclusion: This study
      innovatively uses tumor and Mohs micrographic surgery defect area as a measure of
      morbidity, allowing for identification of populations at need for improved
      education and prevention. (J Clin Aesthet Dermatol. 2016;9(9):16-22.).

PMID- 27878060
TI  - A Retrospective Analysis Comparing the New Standardized Letter of Recommendation
      in Dermatology with the Classic Narrative Letter of Recommendation.
AB  - Background: In an effort to avoid numerous problems associated with narrative
      letters of recommendation, a dermatology standardized letter of recommendation
      was utilized in the 2014-2015 resident application cycle. Objective: A comparison
      of the standardized letter of recommendation and narrative letters of
      recommendation from a single institution and application cycle to determine if
      the standardized letter of recommendation met its original goals of efficiency,
      applicant stratification, and validity. Methods: Eight dermatologists assessed
      all standardized letters of recommendation/narrative letters of recommendation
      pairs received during the 2014-2015 application cycle. Five readers repeated the
      analysis two months later. Each letter of recommendation was evaluated based on a
      seven question survey. Letter analysis and survey completion for each letter was
      timed. Results: Compared to the narrative letters of recommendation, the
      standardized letter of recommendation is easier to interpret (p<0.0001), has less
      exaggeration of applicants' positive traits (p<0.001), and has higher inter-rater
      and intrarater reliability for determining applicant traits including
      personality, reliability, work-ethic, and global score. Standardized letters of
      recommendation are also faster to interpret (p<0.0001) and provide more
      information about the writer's background or writer-applicant relationship than
      narrative letters of recommendation (p<0.001). Limitations: This study was
      completed at a single institution. Conclusions: The standardized letter of
      recommendation appears to be meeting its initial goals of 1) efficiency, 2)
      applicant stratification, and 3) validity. (J Clin Aesthet Dermatol. 2016;9(9):36
      2.).

PMID- 27878061
TI  - Oral Apremilast for the Treatment of Plaque Psoriasis.
AB  - This article provides an update on the use of oral apremilast, a
      phosphodiesterase-4 (PDE4) inhibitor, for the treatment of plaque psoriasis.
      Emphasis is placed on safety evaluations, although efficacy considerations are
      also addressed. Both two-year and three -year data analyses support the favorable
      safety profile reported in pivotal trials with this agent. Although effective in
      many study subjects despite baseline characteristics, higher response rates were
      noted in those with a baseline psoriasis area and severity index (PASI) score <20
      and in subjects not previously treated with systemic therapy for psoriasis.
      Gastrointestinal (GI) side effects are the most common adverse events (AEs)
      reported, especially during the first few weeks of use; recommendations on
      management of GI AEs are discussed. Psychological AEs appear to be rare,
      including with prolonged durations of use, and are not clearly associated with
      the drug itself as depression and suicidal behaviors are common in individuals
      with psoriasis. Data reported through up to 182 weeks of exposure to apremilast
      do not support an association with cardiac AEs, emergence of malignancies,
      enhanced predilection to develop significant opportunistic infections, or
      reactivation of occult infection, such as tuberculosis.

PMID- 27878062
TI  - Pediatric Lichen Sclerosus: A Review of the Literature and Management
      Recommendations.
AB  - Lichen sclerosus is an uncommon, inflammatory disease of the skin and mucosa that
      can cause significant pruritus, pain, and scarring. There are two peaks of
      incidence: one in adult females, and the other in young girls. Early recognition
      and prompt management of the disorder is crucial in preventing long-lasting
      complications. This article reviews lichen sclerosus in children and provides
      evidence-based guidance for treatment in the pediatric population.

PMID- 27878063
TI  - Retrospective Study of Punch Scoring Versus Freehand Approach for First Stage
      Mohs Micrographic Surgery.
AB  - Objective: The objective was to observe whether there is a difference in the
      number of subjects requiring more than one stage of Mohs micrographic surgery for
      small lesion nonmelanoma skin cancers using the punch scoring method versus
      freehand approach. Design: Retrospective review. Setting: Outpatient Mohs Clinic.
      Participants: Thirty patients with small lesion (<5mm) basal cell and squamous
      cell carcinoma who had Mohs micrographic surgery using either the punch scoring
      method (15) for scoring the first layer or the freehand method (15).
      Measurements: Differences between the two groups were evaluated by the number of
      subjects requiring more than one stage and the reason for any additional stages.
      Results: There was no observed difference in the number of subjects requiring
      more than one Mohs stage between the punch scoring group and the freehand group.
      Conclusion: Dermatologic surgeons can use the punch scoring method or the
      freehand approach for scoring small lesion Mohs based on provider preference.

PMID- 27878064
TI  - Cavernous Hemangioma of the Rib: A Case Report.
AB  - Hemangioma of the rib is a rare benign vascular tumor. Herein, we report a 63
      year-old man presenting with hemangioma of the left sixth rib. An osteolytic
      eccentric expansive mass with calcification and focal cortical disruption was
      detected on chest computed tomography (CT). The mass showed low 2-deoxy-2-[18F]
      fluoro-D-glucose (18F-FDG) avidity on positron emission tomography. The patient
      underwent resection of the left sixth rib. Based on the histopathology findings,
      a diagnosis of cavernous hemangioma was made. Rib hemangiomas and malignant
      lesions appear similar on CT scans; therefore, most cases of rib hemangiomas
      reported in the literature were treated with rib resection. However, rib
      hemangiomas should be included in the differential diagnosis of an asymptomatic
      patient if an osteolytic expansive lesion containing sunburst calcifications with
      low 18F-FDG avidity is observed on a CT scan.

PMID- 27878065
TI  - Corticobulbar Tract Involvement in Neuropsychiatric Systemic Lupus Erythematosus:
      A Case Report.
AB  - A 36-year-old woman, diagnosed with systemic lupus erythematosus (SLE), showed
      bulbar symptoms including impaired memory, slurred speech and swallowing
      difficulty 7 days before admission. Magnetic resonance imaging (MRI) showed
      symmetric confluent hyperintensities in the bilateral cerebral white matter on T2
      weighted imaging (T2-WI), extended into the genu of the internal capsule and the
      crus cerebri of the midbrain. MR spectroscopy showed increased choline and
      decreased N-acetyl aspartate (NAA) peak and positron emission computed tomography
      (PET CT) showed decreased fluorodeoxyglucose (FDG) uptake on the lateral portion
      of the frontal lobe, suggesting demyelination of the white matter. The value of
      apparent diffusion coefficient, fractional anisotropy, tensor linear, tensor
      planar and relative anisotropy of the corticobulbar tract (CBT) were lower than
      those of the corticospinal tract. This is the first case report of CBT
      involvement in a patient with neuropsychiatric SLE (NPSLE) as far as we know. The
      findings of T2-WI and diffusion tensor imaging (DTI) showed precise anatomical
      location of neuronal damage of CBT. In addition, magnetic resonance spectroscopy
      (MRS), PET-CT and parameters of DTI supported the explanations of the
      inflammatory process and metabolic change of the white matter caused by NPSLE.

PMID- 27878066
TI  - A Rare Case of Invasive Apocrine Carcinoma of the Breast with Unusual Radiologic
      Findings.
AB  - Invasive apocrine carcinoma (IAC) of the breast is a rare subtype of breast
      malignancy. Its incidence is not well known, but it is approximately less than 1%
      to 4%. For these reasons, there are few reports and little information on the
      radiologic appearance of IAC. Furthermore, most of the case reports show
      malignant features which are similar to invasive ductal carcinoma (IDC). We
      present a rare case of IAC without typical malignant feature on mammography, and
      ultrasonography (USG). Imaging findings on computed tomography (CT), magnetic
      resonance imaging (MRI), and 18F-fluorodeoxyglucose (FDG) positron emission
      tomography (PET)/CT are also presented. The nodule in our case showed a
      relatively benign feature on USG and it is the first case of IAC with unusual
      findings. Therefore, this report may encourage radiologists to consider the
      malignant potential and perform pathologic correlation even if a newly developed
      nodule does not present with a typical malignant feature on USG.

PMID- 27878067
TI  - Ultrasonography Findings of AlloDerm(r) Used in Postmastectomy Alloplastic Breast
      Reconstruction: A Case Report and Literature Review.
AB  - AlloDerm(r) (LifeCell Corp.; Brancburg, NJ) is an acellular dermal matrix (ADM)
      that serves as an immunologically inert scaffold in plastic surgery. In breast
      reconstruction, it is used as a filler for lumpectomy defects and can be used to
      create the inferolateral portion of the tissue expander pocket or implant pocket
      in postmastectomy patients. However, there are limited reports of the radiologic
      findings of AlloDerm(r) in patients who have undergone postmastectomy
      reconstruction. Familiarity with the imaging features of AlloDerm(r) is essential
      for correct diagnosis. We report the ultrasonography features of AlloDerm(r) in a
      43-year-old female patient 3 months after postmastectomy reconstruction. It may
      help distinguish AlloDerm(r) from tumor recurrence or other foreign body
      materials such as gossypiboma. This is important as misdiagnosis can often lead
      to unnecessary surgical intervention.

PMID- 27878068
TI  - Genome methylation patterns across castes and generations in a parasitoid wasp.
AB  - Environmental influences shape phenotypes within and across generations, often
      through DNA methylations that modify gene expression. Methylations were proposed
      to mediate caste and task allocation in some eusocial insects, but how an
      insect's environment affects DNA methylation in its offspring is yet unknown. We
      characterized parental effects on methylation profiles in the polyembryonic
      parasitoid wasp Copidosoma koehleri, as well as methylation patterns associated
      with its simple caste system. We used methylation-sensitive amplified fragment
      length polymorphism (MS-AFLP) to compare methylation patterns, among (1)
      reproductive and soldier larvae; and (2) offspring (larvae, pupae, and adults) of
      wasps that were reared at either high or low larval density and mated in the four
      possible combinations. Methylation frequencies were similar across castes, but
      the profiles of methylated fragments differed significantly. Parental rearing
      density did not affect methylation frequencies in the offspring at any
      developmental stage. Principal coordinate analysis indicated no significant
      differences in methylation profiles among the four crossbreeding groups and the
      three developmental stages. Nevertheless, a clustering analysis, performed on a
      subset of the fragments, revealed similar methylation patterns in larvae, pupae,
      and adults in two of the four parental crosses. Nine fragments were methylated at
      two cytosine sites in all larvae, and five others were methylated at two sites in
      all adults. Thus, DNA methylations correlate with within-generation phenotypic
      plasticity due to caste. However, their association with developmental stage and
      with transgenerational epigenetic effects is not clearly supported.

PMID- 27878069
TI  - Both natural selection and isolation by distance explain phenotypic divergence in
      bill size and body mass between South Australian little penguin colonies.
AB  - Morphological variation between populations of the same species can arise as a
      response to genetic variation, local environmental conditions, or a combination
      of both. In this study, I examined small-scale geographic variation in bill size
      and body mass in little penguins (Eudyptula minor) across five breeding colonies
      in South Australia separated by <150 km. To help understand patterns driving the
      differences, I investigated these variations in relation to environmental
      parameters (air temperature, sea surface temperature, and water depth) and
      geographic distances between the colonies. I found substantial morphological
      variation among the colonies for body mass and bill measurements (except bill
      length). Colonies further located from each other showed greater morphological
      divergence overall than adjacent colonies. In addition, phenotypic traits were
      somewhat correlated to environmental parameters. Birds at colonies surrounded by
      hotter sea surface temperatures were heavier with longer and larger bills. Birds
      with larger and longer bills were also found at colonies surrounded by shallower
      waters. Overall, the results suggest that both environmental factors (natural
      selection) and interpopulation distances (isolation by distance) are causes of
      phenotypic differentiation between South Australian little penguin colonies.

PMID- 27878071
TI  - Flies evolved small bodies and cells at high or fluctuating temperatures.
AB  - Recent theory predicts that the sizes of cells will evolve according to
      fluctuations in body temperature. Smaller cells speed metabolism during periods
      of warming but require more energy to maintain and repair. To evaluate this
      theory, we studied the evolution of cell size in populations of Drosophila
      melanogaster held at either a constant temperature (16 degrees C or 25 degrees C)
      or fluctuating temperatures (16 and 25 degrees C). Populations that evolved at
      fluctuating temperatures or a constant 25 degrees C developed smaller thoraxes,
      wings, and cells than did flies exposed to a constant 16 degrees C. The cells of
      flies from fluctuating environments were intermediate in size to those of flies
      from constant environments. Most genetic variation in cell size was independent
      of variation in wing size, suggesting that cell size was a target of selection.
      These evolutionary patterns accord with patterns of developmental plasticity
      documented previously. Future studies should focus on the mechanisms that
      underlie the selective advantage of small cells at high or fluctuating
      temperatures.

PMID- 27878070
TI  - Changing climate mediates sapsucker (Aves: Sphyrapicus) hybrid zone movement.
AB  - Hybrid zones, where two divergent taxa meet and interbreed, offer unique
      opportunities to investigate how climate contributes to reproductive isolation
      between closely related taxa and how these taxa may respond to climatic changes.
      Red-naped (Sphyrapicus nuchalis) and Red-breasted (Sphyrapicus ruber) sapsuckers
      (Aves: Picidae) hybridize along a narrow contact zone that stretches from
      northern California to British Columbia. The hybrid zone between these species
      has been studied extensively for more than 100 years and represents an excellent
      system for investigations of the evolution of reproductive isolation. Shifts in
      the proportions of phenotypes at hybrid localities since 1910 that were inferred
      using specimens from museum collections were confirmed using species distribution
      models. We predicted the historical, current, and future distributions of
      parental and hybrid sapsuckers using Random Forests models to quantify how
      climate change is affecting hybrid zone movement in the Pacific Northwest. We
      found observed distribution shifts of parental sapsuckers were likely the result
      of climate change over the past 100 years, with these shifts predicted to
      continue for both sapsuckers over the next 80 years. We found Red-breasted
      Sapsuckers are predicted to continue to expand, while Red-naped Sapsuckers are
      predicted to contract substantially under future climate scenarios. As a result
      of the predicted changes, the amount of overlap in the distribution of these
      sapsuckers may decrease. Using hybrid phenotypes, we found the climate niche
      occupied by the hybrid zone is predicted to disappear under future conditions.
      The disappearance of this climate niche where the two parental species come into
      contact and hybridize may lead to a substantial reduction in genetic
      introgression. Understanding the impacts of global climate change on hybrid zones
      may help us to better understand how speciation has been shaped by climate in the
      past, as well as how evolution may respond to climate change in the future.

PMID- 27878072
TI  - Concordance between stabilizing sexual selection, intraspecific variation, and
      interspecific divergence in Phymata.
AB  - Empirical studies show that lineages typically exhibit long periods of
      evolutionary stasis and that relative levels of within-species trait covariance
      often correlate with the extent of between-species trait divergence. These
      observations have been interpreted by some as evidence of genetic constraints
      persisting for long periods of time. However, an alternative explanation is that
      both intra- and interspecific variation are shaped by the features of the
      adaptive landscape (e.g., stabilizing selection). Employing a genus of insects
      that are diverse with respect to a suite of secondary sex traits, we related data
      describing nonlinear phenotypic (sexual) selection to intraspecific trait
      covariances and macroevolutionary divergence. We found support for two key
      predictions (1) that intraspecific trait covariation would be aligned with
      stabilizing selection and (2) that there would be restricted macroevolutionary
      divergence in the direction of stabilizing selection. The observed alignment of
      all three matrices offers a point of caution in interpreting standing variability
      as metrics of evolutionary constraint. Our results also illustrate the power of
      sexual selection for determining variation observed at both short and long
      timescales and account for the apparently slow evolution of some secondary sex
      characters in this lineage.

PMID- 27878073
TI  - Does the different photosynthetic pathway of plants affect soil respiration in a
      subtropical wetland?
AB  - Plants with different photosynthetic pathways could produce different amounts and
      types of root exudates and debris which may affect soil respiration rates.
      Therefore, wetland vegetation succession between plants with different
      photosynthetic pathways may ultimately influence the wetland carbon budget. The
      middle and lower reaches of the Yangtze River has the largest floodplain wetland
      group in China. Tian'e Zhou wetland reserve (29 degrees 48'N, 112 degrees 33'E)
      is located in Shishou city, Hubei province and covers about 77.5 square
      kilometers. Hemathria altissima (C4) was found gradually being replaced by Carex
      argyi (C3) for several years in this place. An in situ experiment was conducted
      in Tian'e Zhou wetland to determine the change of soil respiration as the
      succession proceeds. Soil respiration, substrate-induced respiration, and
      bacterial respiration of the C4 species was greater than those of the C3 species,
      but below-ground biomass and fungal respiration of the C4 species was less than
      that of the C3 species. There were no significant differences in above-ground
      biomass between the two species. Due to the higher photosynthesis capability,
      higher soil respiration and lower total plant biomass, we inferred that the C4
      species, H. altissima, may transport more photosynthate below-ground as a
      substrate for respiration. The photosynthetic pathway of plants might therefore
      play an important role in regulating soil respiration. As C. argyi replaces H.
      altissima, the larger plant biomass and lower soil respiration would indicate
      that the wetland in this area could fix more carbon in the soil than before.

PMID- 27878074
TI  - Latitudinal variation in nematode diversity and ecological roles along the
      Chinese coast.
AB  - AIM: To test changes in the phylogenetic relatedness, niche breadth, and life
      history strategies of nematodes along a latitudinal gradient. LOCATION: Sixteen
      wetland locations along the Pacific coast of China, from 20 degrees N to 40
      degrees N. METHODS: Linear regression was used to relate nematode phylogenetic
      relatedness (average taxonomic distinctness (AvTD) and average phylogenetic
      diversity [AvPD]), life-history group (based on "c-p" colonizer-persister group
      classification), and dietary specificity (based on guild classification of
      feeding selectivity) to latitude. RESULTS: Wetland nematode taxonomic diversity
      (richness and Shannon diversity indices) decreased with increasing latitude along
      the Chinese coast. Phylogenetic diversity indices (AvTD and AvPD) significantly
      increased with increasing latitude. This indicates that at lower latitudes,
      species within the nematode community were more closely related. With increasing
      latitude, the nematode relative richness and abundance decreased for selective
      deposit feeders but increased for nonselective deposit feeders. The proportion of
      general opportunists decreased with increasing latitude, but persisters showed
      the opposite trend. The annual temperature range and the pH of sediments were
      more important than vegetation type in structuring nematode communities. MAIN
      CONCLUSION: Nematode niche breadth was narrower at lower latitudes with respect
      to dietary specificity. Higher latitudes with a more variable climate favor r
      over K life-history strategists. Nematode communities at lower latitudes
      contained more closely related species.

PMID- 27878076
TI  - Nonmotorized recreation and motorized recreation in shrub-steppe habitats affects
      behavior and reproduction of golden eagles (Aquila chrysaetos).
AB  - Different forms of outdoor recreation have different spatiotemporal activity
      patterns that may have interactive or cumulative effects on wildlife through
      human disturbance, physical habitat change, or both. In western North America,
      shrub-steppe habitats near urban areas are popular sites for motorized recreation
      and nonmotorized recreation and can provide important habitat for protected
      species, including golden eagles. Our objective was to determine whether
      recreation use (i.e., number of recreationists) or recreation features (e.g.,
      trails or campsites) predicted golden eagle territory occupancy, egg-laying, or
      the probability a breeding attempt resulted in >=1 offspring (nest survival). We
      monitored egg-laying, hatching and fledging success, eagle behavior, and
      recreation activity within 23 eagle territories near Boise, Idaho, USA.
      Territories with more off-road vehicle (ORV) use were less likely to be occupied
      than territories with less ORV use (beta = -1.6, 85% CI: -2.8 to -0.8). At
      occupied territories, early season pedestrian use (beta = -1.6, 85% CI: -3.8 to 
      0.2) and other nonmotorized use (beta = -3.6, 85% CI: -10.7 to -0.3) reduced the
      probability of egg-laying. At territories where eagles laid eggs, short, interval
      specific peaks in ORV use were associated with decreased nest survival (beta = 
      0.5, 85% CI: -0.8 to -0.2). Pedestrians, who often arrived near eagle nests via
      motorized vehicles, were associated with reduced nest attendance (beta = -11.9,
      85% CI: -19.2 to -4.5), an important predictor of nest survival. Multiple forms
      of recreation may have cumulative effects on local populations by reducing
      occupancy at otherwise suitable territories, decreasing breeding attempts, and
      causing nesting failure. Seasonal no-stopping zones for motorized vehicles may be
      an alternative to trail closures for managing disturbance. This study
      demonstrates the importance of considering human disturbance across different
      parts of the annual cycle, particularly where multiple forms of recreation have
      varying spatiotemporal use patterns that create human-wildlife interactions.

PMID- 27878075
TI  - Experimentally comparing the attractiveness of domestic lights to insects: Do
      LEDs attract fewer insects than conventional light types?
AB  - LED lighting is predicted to constitute 70% of the outdoor and residential
      lighting markets by 2020. While the use of LEDs promotes energy and cost savings
      relative to traditional lighting technologies, little is known about the effects
      these broad-spectrum "white" lights will have on wildlife, human health, animal
      welfare, and disease transmission. We conducted field experiments to compare the
      relative attractiveness of four commercially available "domestic" lights, one
      traditional (tungsten filament) and three modern (compact fluorescent, "cool
      white" LED and "warm-white" LED), to aerial insects, particularly Diptera. We
      found that LEDs attracted significantly fewer insects than other light sources,
      but found no significant difference in attraction between the "cool-" and "warm
      white" LEDs. Fewer flies were attracted to LEDs than alternate light sources,
      including fewer Culicoides midges (Diptera: Ceratopogonidae). Use of LEDs has the
      potential to mitigate disturbances to wildlife and occurrences of insect-borne
      diseases relative to competing lighting technologies. However, we discuss the
      risks associated with broad-spectrum lighting and net increases in lighting
      resulting from reduced costs of LED technology.

PMID- 27878077
TI  - Phylogeography of the antilopine wallaroo (Macropus antilopinus) across tropical
      northern Australia.
AB  - The distribution of antilopine wallaroo, Macropus antilopinus, is marked by a
      break in the species' range between Queensland and the Northern Territory,
      coinciding with the Carpentarian barrier. Previous work on M. antilopinus
      revealed limited genetic differentiation between the Northern Territory and
      Queensland M. antilopinus populations across this barrier. The study also
      identified a number of divergent lineages in the Northern Territory, but was
      unable to elucidate any geographic structure. Here, we re-examine these results
      to (1) determine phylogeographic patterns across the range of M. antilopinus and
      (2) infer the biogeographic barriers associated with these patterns. The tropical
      savannahs of northern Australia: from the Cape York Peninsula in the east, to the
      Kimberley in the west. We examined phylogeographic patterns in M. antilopinus
      using a larger number of samples and three mtDNA genes: NADH dehydrogenase
      subunit 2, cytochrome b, and the control region. Two datasets were generated and
      analyzed: (1) a subset of samples with all three mtDNA regions concatenated
      together and (2) all samples for just control region sequences that included
      samples from the previous study. Analysis included generating phylogenetic trees
      based on Bayesian analysis and intraspecific median-joining networks. The
      contemporary spatial structure of M. antilopinus mtDNA lineages revealed five
      shallow clades and a sixth, divergent lineage. The genetic differences that we
      found between Queensland and Northern Territory M. antilopinus samples confirmed
      the split in the geographic distribution of the species. We also found weak
      genetic differentiation between Northern Territory samples and those from the
      Kimberley region of Western Australia, possibly due to the Kimberley Plateau
      Arnhem Land barrier. Within the Northern Territory, two clades appear to be
      parapatric in the west, while another two clades are broadly sympatric across the
      Northern Territory. MtDNA diversity of M. antilopinus revealed an unexpectedly
      complex evolutionary history involving multiple sympatric and parapatric mtDNA
      clades across northern Australia. These phylogeographic patterns highlight the
      importance of investigating genetic variation across distributions of species and
      integrating this information into biodiversity conservation.

PMID- 27878078
TI  - Cool habitats support darker and bigger butterflies in Australian tropical
      forests.
AB  - Morphology mediates the relationship between an organism's body temperature and
      its environment. Dark organisms, for example, tend to absorb heat more quickly
      than lighter individuals, which could influence their responses to temperature.
      Therefore, temperature-related traits such as morphology may affect patterns of
      species abundance, richness, and community assembly across a broad range of
      spatial scales. In this study, we examined variation in color lightness and body
      size within butterfly communities across hot and cool habitats in the tropical
      woodland-rainforest ecosystems of northeast Queensland, Australia. Using thermal
      imaging, we documented the absorption of solar radiation relative to color
      lightness and wingspan and then built a phylogenetic tree based on available
      sequences to analyze the effects of habitat on these traits within a phylogenetic
      framework. In general, darker and larger individuals were more prevalent in cool,
      closed-canopy rainforests than in immediately adjacent and hotter open woodlands.
      In addition, darker and larger butterflies preferred to be active in the shade
      and during crepuscular hours, while lighter and smaller butterflies were more
      active in the sun and midday hours-a pattern that held after correcting for
      phylogeny. Our ex situ experiment supported field observations that dark and
      large butterflies heated up faster than light and small butterflies under
      standardized environmental conditions. Our results show a thermal consequence of
      butterfly morphology across habitats and how environmental factors at a
      microhabitat scale may affect the distribution of species based on these traits.
      Furthermore, this study highlights how butterfly species might differentially
      respond to warming based on ecophysiological traits and how thermal refuges might
      emerge at microclimatic and habitat scales.

PMID- 27878079
TI  - Microbial community responses to soil tillage and crop rotation in a corn/soybean
      agroecosystem.
AB  - The acreage planted in corn and soybean crops is vast, and these crops contribute
      substantially to the world economy. The agricultural practices employed for
      farming these crops have major effects on ecosystem health at a worldwide scale.
      The microbial communities living in agricultural soils significantly contribute
      to nutrient uptake and cycling and can have both positive and negative impacts on
      the crops growing with them. In this study, we examined the impact of the crop
      planted and soil tillage on nutrient levels, microbial communities, and the
      biochemical pathways present in the soil. We found that farming practice, that is
      conventional tillage versus no-till, had a much greater impact on nearly
      everything measured compared to the crop planted. No-till fields tended to have
      higher nutrient levels and distinct microbial communities. Moreover, no-till
      fields had more DNA sequences associated with key nitrogen cycle processes,
      suggesting that the microbial communities were more active in cycling nitrogen.
      Our results indicate that tilling of agricultural soil may magnify the degree of
      nutrient waste and runoff by altering nutrient cycles through changes to
      microbial communities. Currently, a minority of acreage is maintained without
      tillage despite clear benefits to soil nutrient levels, and a decrease in
      nutrient runoff-both of which have ecosystem-level effects and both direct and
      indirect effects on humans and other organisms.

PMID- 27878080
TI  - Intragenomic conflict produces sex ratio dynamics that favor maternal sex ratio
      distorters.
AB  - Maternal sex ratio distorters (MSDs) are selfish elements that enhance their
      transmission by biasing their host's sex allocation in favor of females. While
      previous models have predicted that the female-biased populations resulting from
      sex ratio distortion can benefit from enhanced productivity, these models neglect
      Fisherian selection for nuclear suppressors, an unrealistic assumption in most
      systems. We used individual-based computer simulation modeling to explore the
      intragenomic conflict between sex ratio distorters and their suppressors and
      explored the impacts of these dynamics on population-level competition between
      species characterized by MSDs and those lacking them. The conflict between
      distorters and suppressors was capable of producing large cyclical fluctuations
      in the population sex ratio and reproductive rate. Despite fitness costs
      associated with the distorters and suppressors, MSD populations often exhibited
      enhanced productivity and outcompeted non-MSD populations in single and multiple
      population competition simulations. Notably, the conflict itself is beneficial to
      the success of populations, as sex ratio oscillations limit the competitive
      deficits associated with prolonged periods of male rarity. Although intragenomic
      conflict has been historically viewed as deleterious to populations, our results
      suggest that distorter-suppressor conflict can provide population-level
      advantages, potentially helping to explain the persistence of sex ratio
      distorters in a range of taxa.

PMID- 27878081
TI  - Climate extremes are associated with invertebrate taxonomic and functional
      composition in mountain lakes.
AB  - Climate change is expected to increase climate variability and the occurrence of
      extreme climatic events, with potentially devastating effects on aquatic
      ecosystems. However, little is known about the role of climate extremes in
      structuring aquatic communities or the interplay between climate and local
      abiotic and biotic factors. Here, we examine the relative influence of climate
      and local abiotic and biotic conditions on biodiversity and community structure
      in lake invertebrates. We sampled aquatic invertebrates and measured
      environmental variables in 19 lakes throughout California, USA, to test
      hypotheses of the relationship between climate, local biotic and environmental
      conditions, and the taxonomic and functional structure of aquatic invertebrate
      communities. We found that, while local biotic and abiotic factors such as
      habitat availability and conductivity were the most consistent predictors of
      alpha diversity, extreme climate conditions such as maximum summer temperature
      and dry-season precipitation were most often associated with multivariate
      taxonomic and functional composition. Specifically, sites with high maximum
      temperatures and low dry-season precipitation housed communities containing high
      abundances of large predatory taxa. Furthermore, both climate dissimilarity and
      abiotic dissimilarity determined taxonomic turnover among sites (beta diversity).
      These findings suggest that while local-scale environmental variables may predict
      alpha diversity, climatic variability is important to consider when projecting
      broad-scale aquatic community responses to the extreme temperature and
      precipitation events that are expected for much of the world during the next
      century.

PMID- 27878082
TI  - Predicted rarity-weighted richness, a new tool to prioritize sites for species
      representation.
AB  - Lack of biodiversity data is a major impediment to prioritizing sites for species
      representation. Because comprehensive species data are not available in any
      planning area, planners often use surrogates (such as vegetation communities, or
      mapped occurrences of a well-inventoried taxon) to prioritize sites. We propose
      and demonstrate the effectiveness of predicted rarity-weighted richness (PRWR) as
      a surrogate in situations where species inventories may be available for a
      portion of the planning area. Use of PRWR as a surrogate involves several steps.
      First, rarity-weighted richness (RWR) is calculated from species inventories for
      a q% subset of sites. Then random forest models are used to model RWR as a
      function of freely available environmental variables for that q% subset. This
      function is then used to calculate PRWR for all sites (including those for which
      no species inventories are available), and PRWR is used to prioritize all sites.
      We tested PRWR on plant and bird datasets, using the species accumulation index
      to measure efficiency of PRWR. Sites with the highest PRWR represented species
      with median efficiency of 56% (range 32%-77% across six datasets) when q = 20%,
      and with median efficiency of 39% (range 20%-63%) when q = 10%. An efficiency of
      56% means that selecting sites in order of PRWR rank was 56% as effective as
      having full knowledge of species distributions in PRWR's ability to improve on
      the number of species represented in the same number of randomly selected sites.
      Our results suggest that PRWR may be able to help prioritize sites to represent
      species if a planner has species inventories for 10%-20% of the sites in the
      planning area.

PMID- 27878083
TI  - Interactive effects between plant functional types and soil factors on tundra
      species diversity and community composition.
AB  - Plant communities are coupled with abiotic factors, as species diversity and
      community composition both respond to and influence climate and soil
      characteristics. Interactions between vegetation and abiotic factors depend on
      plant functional types (PFT) as different growth forms will have differential
      responses to and effects on site characteristics. However, despite the importance
      of different PFT for community assembly and ecosystem functioning, research has
      mainly focused on vascular plants. Here, we established a set of observational
      plots in two contrasting habitats in northeastern Siberia in order to assess the
      relationship between species diversity and community composition with soil
      variables, as well as the relationship between vegetation cover and species
      diversity for two PFT (nonvascular and vascular). We found that nonvascular
      species diversity decreased with soil acidity and moisture and, to a lesser
      extent, with soil temperature and active layer thickness. In contrast, no such
      correlation was found for vascular species diversity. Differences in community
      composition were found mainly along soil acidity and moisture gradients. However,
      the proportion of variation in composition explained by the measured soil
      variables was much lower for nonvascular than for vascular species when
      considering the PFT separately. We also found different relationships between
      vegetation cover and species diversity according the PFT and habitat. In support
      of niche differentiation theory, species diversity and community composition were
      related to edaphic factors. The distinct relationships found for nonvascular and
      vascular species suggest the importance of considering multiple PFT when
      assessing species diversity and composition and their interaction with edaphic
      factors. Synthesis: Identifying vegetation responses to edaphic factors is a
      first step toward a better understanding of vegetation-soil feedbacks under
      climate change. Our results suggest that incorporating differential responses of
      PFT is important for predicting vegetation shifts, primary productivity, and in
      turn, ecosystem functioning in a changing climate.

PMID- 27878084
TI  - Effect of different root endophytic fungi on plant community structure in
      experimental microcosms.
AB  - Understanding the effects of root-associated microbes in explaining plant
      community patterns represents a challenge in community ecology. Although
      typically overlooked, several lines of evidence point out that nonmycorrhizal,
      root endophytic fungi in the Ascomycota may have the potential to drive changes
      in plant community ecology given their ubiquitous presence, wide host ranges, and
      plant species-specific fitness effects. Thus, we experimentally manipulated the
      presence of root endophytic fungal species in microcosms and measured its effects
      on plant communities. Specifically, we tested whether (1) three different root
      endophyte species can modify plant community structure; (2) those changes can
      also modified the way plant respond to different soil types; and (3) the effects
      are modified when all the fungi are present. As a model system, we used plant and
      fungal species that naturally co-occur in a temperate grassland. Further, the
      soil types used in our experiment reflected a strong gradient in soil texture
      that has been shown to drive changes in plant and fungal community structure in
      the field. Results showed that each plant species responded differently to
      infection, resulting in distinct patterns of plant community structure depending
      on the identity of the fungus present. Those effects depended on the soil type.
      For example, large positive effects due to presence of the fungi were able to
      compensate for less nutrients levels in one soil type. Further, host responses
      when all three fungi were present were different from the ones observed in single
      fungal inoculations, suggesting that endophyte-endophyte interactions may be
      important in structuring plant communities. Overall, these results indicate that
      plant responses to changes in the species identity of nonmycorrhizal fungal
      community species and their interactions can modify plant community structure.

PMID- 27878085
TI  - Stable isotope-based trophic structure of pelagic fish and jellyfish across
      natural and anthropogenic landscape gradients in a fjord estuary.
AB  - Identifying causes of structural ecosystem shifts often requires understanding
      trophic structure, an important determinant of energy flow in ecological
      communities. In coastal pelagic ecosystems worldwide, increasing jellyfish
      (Cnidaria and Ctenophora) at the expense of small fish has been linked to
      anthropogenic alteration of basal trophic pathways. However, this hypothesis
      remains untested in part because baseline description of fish-jellyfish trophic
      dynamics, and the environmental features that influence them are lacking. Using
      stable isotopes of carbon (delta13C) and nitrogen (delta15N), we examined
      spatiotemporal patterns of fish and jellyfish trophic structure in greater Puget
      Sound, an urbanizing fjord estuary in the NW United States. We quantified niche
      positions of constituent species, niche widths and trophic overlap between fish
      and jellyfish assemblages, and several community-level trophic diversity metrics
      (resource diversity, trophic length, and niche widths) of fish and jellyfish
      combined. We then related assemblage- and community-level measures to landscape
      gradients of terrestrial-marine connectivity and anthropogenic influence in
      adjacent catchments. Relative niche positions among species varied considerably
      and displayed no clear pattern except that fish generally had higher delta15N and
      lower delta13C relative to jellyfish, which resulted in low assemblage-level
      trophic overlap. Fish assemblages had larger niche widths than jellyfish in most
      cases and, along with whole community trophic diversity, exhibited contrasting
      seasonal patterns across oceanographic basins, which was positively correlated to
      landscape variation in terrestrial connectivity. In contrast, jellyfish niche
      widths were unrelated to terrestrial connectivity, but weakly negatively
      correlated to urban land use in adjacent catchments. Our results indicate that
      fish-jellyfish trophic structure is highly heterogeneous and that disparate
      processes may underlie the trophic ecology of these taxa; consequently, they may
      respond divergently to environmental change. In addition, spatiotemporal
      variation in ecosystem connectivity, in this case through freshwater influence,
      may influence trophic structure across heterogeneous landscapes.

PMID- 27878086
TI  - Impact of urbanization and gardening practices on common butterfly communities in
      France.
AB  - We investigated the interacting impacts of urban landscape and gardening
      practices on the species richness and total abundance of communities of common
      butterfly communities across France, using data from a nationwide monitoring
      scheme. We show that urbanization has a strong negative impact on butterfly
      richness and abundance but that at a local scale, such impact could be mitigated
      by gardening practices favoring nectar offer. We found few interactions among
      these landscape and local scale effects, indicating that butterfly-friendly
      gardening practices are efficient whatever the level of surrounding urbanization.
      We further highlight that species being the most negatively affected by
      urbanization are the most sensitive to gardening practices: Garden management can
      thus partly counterbalance the deleterious effect of urbanization for butterfly
      communities. This holds a strong message for park managers and private gardeners,
      as gardens may act as potential refuge for butterflies when the overall landscape
      is largely unsuitable.

PMID- 27878087
TI  - Collateral damage to marine and terrestrial ecosystems from Yankee whaling in the
      19th century.
AB  - Yankee whalers of the 19th century had major impacts on populations of large
      whales, but these leviathans were not the only taxa targeted. Here, we describe
      the "collateral damage," the opportunistic or targeted taking of nongreat whale
      species by the American whaling industry. Using data from 5,064 records from 79
      whaling logs occurring between 1840 and 1901, we show that Yankee whalers
      captured 5,255 animals across three large ocean basins from 32 different
      taxonomic categories, including a wide range of marine and terrestrial species.
      The taxa with the greatest number of individuals captured were walruses (Odobenus
      rosmarus), ducks (family Anatidae), and cod (Gadus sp.). By biomass, the most
      captured species were walruses, grampus (a poorly defined group within
      Odontoceti), and seals (family Otariidae). The whalers captured over 2.4 million
      kg of nongreat whale meat equaling approximately 34 kg of meat per ship per day
      at sea. The species and areas targeted shifted over time in response to
      overexploitation of whale populations, with likely intensive local impacts on
      terrestrial species associated with multiyear whaling camps. Our results show
      that the ecosystem impacts of whaling reverberated on both marine and coastal
      environments.

PMID- 27878088
TI  - Dispersal and group formation dynamics in a rare and endangered temperate forest
      bat (Nyctalus lasiopterus, Chiroptera: Vespertilionidae).
AB  - For elusive mammals like bats, colonization of new areas and colony formation are
      poorly understood, as is their relationship with the genetic structure of
      populations. Understanding dispersal and group formation behaviors is critical
      not only for a better comprehension of mammalian social dynamics, but also for
      guiding conservation efforts of rare and endangered species. Using nuclear and
      mitochondrial markers, we studied patterns of genetic diversity and
      differentiation among and within breeding colonies of giant noctule bats
      (Nyctalus lasiopterus), their relation to a new colony still in formation, and
      the impact of this ongoing process on the regionwide genetic makeup. Nuclear
      differentiation among colonies was relatively low and mostly nonsignificant.
      Mitochondrial variation followed this pattern, contrasting with findings for
      other temperate bat species. Our results suggest that this may indicate a recent
      population expansion. On average, female giant noctules were not more closely
      related to other colony members than to foreign individuals. This was also true
      for members of the newly forming colony and those of another, older group sampled
      shortly after its formation, suggesting that contrary to findings for other
      temperate bats, giant noctule colonies are not founded by relatives. However,
      mother-daughter pairs were found in the same populations more often than expected
      under random dispersal. Given this indication of philopatry, the lack of
      mitochondrial differentiation among most colonies in the region is probably due
      to the combination of a recent population expansion and group formation events.

PMID- 27878089
TI  - Phylogenetic relationships of freshwater fishes of the genus Capoeta
      (Actinopterygii, Cyprinidae) in Iran.
AB  - The Middle East contains a great diversity of Capoeta species, but their taxonomy
      remains poorly described. We used mitochondrial history to examine diversity of
      the algae-scraping cyprinid Capoeta in Iran, applying the species-delimiting
      approaches General Mixed Yule-Coalescent (GMYC) and Poisson Tree Process (PTP) as
      well as haplotype network analyses. Using the BEAST program, we also examined
      temporal divergence patterns of Capoeta. The monophyly of the genus and the
      existence of three previously described main clades (Mesopotamian, Anatolian
      Iranian, and Aralo-Caspian) were confirmed. However, the phylogeny proposed novel
      taxonomic findings within Capoeta. Results of GMYC, bPTP, and phylogenetic
      analyses were similar and suggested that species diversity in Iran is currently
      underestimated. At least four candidate species, Capoeta sp4, Capoeta sp5,
      Capoeta sp6, and Capoeta sp7, are awaiting description. Capoeta capoeta comprises
      a species complex with distinct genetic lineages. The divergence times of the
      three main Capoeta clades are estimated to have occurred around 15.6-12.4 Mya,
      consistent with a Mio-Pleistocene origin of the diversity of Capoeta in Iran. The
      changes in Caspian Sea levels associated with climate fluctuations and
      geomorphological events such as the uplift of the Zagros and Alborz Mountains may
      account for the complex speciation patterns in Capoeta in Iran.

PMID- 27878090
TI  - Species mixture effects on flammability across plant phylogeny: the importance of
      litter particle size and the special role for non-Pinus Pinaceae.
AB  - Fire affects and is affected by plants. Vegetation varies in flammability, that
      is, its general ability to burn, at different levels of ecological organization.
      To scale from individual plant traits to community flammability states,
      understanding trait effects on species flammability variation and their
      interaction is important. Plant traits are the cumulative result of evolution and
      they show, to differing extents, phylogenetic conservatism. We asked whether
      phylogenetic distance between species predicts species mixture effects on
      litterbed flammability. We conducted controlled laboratory burns for 34
      phylogenetically wide-ranging species and 34 random two-species mixtures from
      them. Generally, phylogenetic distance did not predict species mixture effects on
      flammability. Across the plant phylogeny, most species were flammable except
      those in the non-Pinus Pinaceae, which shed small needles producing dense, poorly
      ventilated litterbeds above the packing threshold and therefore nonflammable.
      Consistently, either positive or negative dominance effects on flammability of
      certain flammable or those non-flammable species were found in mixtures involving
      the non-Pinus Pinaceae. We demonstrate litter particle size is key to explaining
      species nonadditivity in fuelbed flammability. The potential of certain species
      to influence fire disproportionately to their abundance might increase the
      positive feedback effects of plant flammability on community flammability state
      if flammable species are favored by fire.

PMID- 27878092
TI  - Putting the behavior into animal movement modeling: Improved activity budgets
      from use of ancillary tag information.
AB  - Animal movement research relies on biotelemetry, and telemetry-based locations
      are increasingly augmented with ancillary information. This presents an
      underutilized opportunity to enhance movement process models. Given tags designed
      to record specific behaviors, efforts are increasing to update movement models
      beyond reliance solely upon horizontal movement information to improve inference
      of space use and activity budgets. We present two state-space models adapted to
      incorporate ancillary data to inform three discrete movement states: directed,
      resident, and an activity state. These were developed for two case studies: (1) a
      "haulout" model for Weddell seals, and (2) an "activity" model for Antarctic fur
      seals which intersperse periods of diving activity and inactivity. The
      methodology is easily implementable with any ancillary data that can be expressed
      as a proportion (or binary) indicator. A comparison of the models augmented with
      ancillary information and unaugmented models confirmed that many behavioral
      states appeared mischaracterized in the latter. Important changes in subsequent
      activity budgets occurred. Haulout accounted for 0.17 of the overall Weddell seal
      time budget, with the estimated proportion of time spent in a resident state
      reduced from a posterior median of 0.69 (0.65-0.73; 95% HPDI) to 0.54 (0.50-0.58
      HPDI). The drop was more dramatic in the Antarctic fur seal case, from 0.57 (0.52
      0.63 HPDI) to 0.22 (0.20-0.25 HPDI), with 0.35 (0.31-0.39 HPDI) of time spent in
      the inactive (nondiving) state. These findings reinforce previously raised
      contentions about the drawbacks of behavioral states inferred solely from
      horizontal movements. Our findings have implications for assessing habitat
      requirements; estimating energetics and consumption; and management efforts such
      as mitigating fisheries interactions. Combining multiple sources of information
      within integrated frameworks should improve inference of relationships between
      movement decisions and fitness, the interplay between resource and habitat
      dependencies, and their changes at the population and landscape level.

PMID- 27878091
TI  - Diversity and resilience of the wood-feeding higher termite Mironasutitermes
      shangchengensis gut microbiota in response to temporal and diet variations.
AB  - Termites are considered among the most efficient bioreactors, with high
      capacities for lignocellulose degradation and utilization. Recently, several
      studies have characterized the gut microbiota of diverse termites. However, the
      temporal dynamics of the gut microbiota within a given termite with dietary
      diversity are poorly understood. Here, we employed 16S rDNA barcoded
      pyrosequencing analysis to investigate temporal changes in bacterial diversity
      and richness of the gut microbiota of wood-feeding higher termite
      Mironasutitermes shangchengensis under three lignocellulose content-based diets
      that feature wood, corn stalks, and filter paper. Compositions of the predominant
      termite gut residents were largely constant among the gut microbiomes under
      different diets, but each diet caused specific changes in the bacterial
      composition over time. Notably, microbial communities exhibited an unexpectedly
      strong resilience during continuous feeding on both corn stalks and filter paper.
      Members of five bacterial phyla, that is, Spirochaetes, Firmicutes,
      Actinobacteria, Tenericutes, and Acidobacteria, were strongly associated with the
      resilience. These findings provide insights into the stability of the gut
      microbiota in higher termites and have important implications for the future
      design of robust bioreactors for lignocellulose degradation and utilization.

PMID- 27878093
TI  - Effects of environmental factors on genetic diversity of Caragana microphylla in
      Horqin Sandy Land, northeast China.
AB  - Caragana microphylla (Leguminosae) is a dominant climax semishrub species in
      northern China. We evaluated genetic variation within and among populations
      sampled from three different environmental gradients in Horqin Sandy Land in
      northern China using intersimple sequence repeats markers and investigated the
      possible existence of relationships between genetic diversity and environmental
      factors. The results showed that C. microphylla have high genetic diversity, and
      environmental gradients affected genetic diversity of C. microphylla populations.
      Genetic diversity of all populations was affected by many environmental factors
      and as well correlated with warm index and soil Olsen phosphorus (SOP)
      concentration. These results have important implications for restoration and
      management of these degraded ecosystems in arid and semi-arid areas.

PMID- 27878094
TI  - Host-mediated shift in the cold tolerance of an invasive insect.
AB  - While many insects cannot survive the formation of ice within their bodies, a few
      species can. On the evolutionary continuum from freeze-intolerant (i.e., freeze
      avoidant) to freeze-tolerant insects, intermediates likely exist that can
      withstand some ice formation, but not enough to be considered fully freeze
      tolerant. Theory suggests that freeze tolerance should be favored over freeze
      avoidance among individuals that have low relative fitness before exposure to
      cold. For phytophagous insects, numerous studies have shown that host (or
      nutrition) can affect fitness and cold-tolerance strategy, respectively, but no
      research has investigated whether changes in fitness caused by different hosts of
      polyphagous species could lead to systematic changes in cold-tolerance strategy.
      We tested this relationship with the invasive, polyphagous moth, Epiphyas
      postvittana (Walker). Host affected components of fitness, such as larval
      survivorship rates, pupal mass, and immature developmental times. Host species
      also caused a dramatic change in survival of late-instar larvae after the onset
      of freezing-from less than 8% to nearly 80%. The degree of survival after the
      onset of freezing was inversely correlated with components of fitness in the
      absence of cold exposure. Our research is the first empirical evidence of an
      evolutionary mechanism that may drive changes in cold-tolerance strategies.
      Additionally, characterizing the effects of host plants on insect cold tolerance
      will enhance forecasts of invasive species dynamics, especially under climate
      change.

PMID- 27878095
TI  - On the influence of provenance to soil quality enhanced stress reaction of young
      beech trees to summer drought.
AB  - Climate projections propose that drought stress will become challenging for
      establishing trees. The magnitude of stress is dependent on tree species,
      provenance, and most likely also highly influenced by soil quality. European
      Beech (Fagus sylvatica) is of major ecological and economical importance in
      Central European forests. The species has an especially wide physiological and
      ecological amplitude enabling growth under various soil conditions within its
      distribution area in Central Europe. We studied the effects of extreme drought on
      beech saplings (second year) of four climatically distinct provenances growing on
      different soils (sandy loam and loamy sand) in a full factorial pot experiment.
      Foliar delta13C, delta15N, C, and N as well as above- and belowground growth
      parameters served as measures for stress level and plant growth. Low-quality soil
      enhanced the effect of drought compared with qualitatively better soil for the
      above- and belowground growth parameters, but foliar delta13C values revealed
      that plant stress was still remarkable in loamy soil. For beeches of one
      provenance, negative sandy soil effects were clearly smaller than for the others,
      whereas for another provenance drought effects in sandy soil were sometimes
      fatal. Foliar delta15N was correlated with plant size during the experiment.
      Plasticity of beech provenances in their reaction to drought versus control
      conditions varied clearly. Although a general trend of declining growth under
      control or drought conditions in sandy soil was found compared to loamy soil, the
      magnitude of the effect of soil quality was highly provenance specific.
      Provenances seemed to show adaptations not only to drought but also to soil
      quality. Accordingly, scientists should integrate information about climatic pre
      adaptation and soil quality within the home range of populations for species
      distribution modeling and foresters should evaluate soil quality and climatic
      parameters when choosing donor populations for reforestation projects.

PMID- 27878096
TI  - A sixth-level habitat cascade increases biodiversity in an intertidal estuary.
AB  - Many studies have documented habitat cascades where two co-occurring habitat
      forming species control biodiversity. However, more than two habitat-formers
      could theoretically co-occur. We here documented a sixth-level habitat cascade
      from the Avon-Heathcote Estuary, New Zealand, by correlating counts of attached
      inhabitants to the size and accumulated biomass of their biogenic hosts. These
      data revealed predictable sequences of habitat-formation (=attachment space).
      First, the bivalve Austrovenus provided habitat for green seaweeds (Ulva) that
      provided habitat for trochid snails in a typical estuarine habitat cascade.
      However, the trochids also provided habitat for the nonnative bryozoan Conopeum
      that provided habitat for the red seaweed Gigartina that provided habitat for
      more trochids, thereby resetting the sequence of the habitat cascade,
      theoretically in perpetuity. Austrovenus is here the basal habitat-former that
      controls this "long" cascade. The strength of facilitation increased with seaweed
      frond size, accumulated seaweed biomass, accumulated shell biomass but less with
      shell size. We also found that Ulva attached to all habitat-formers, trochids
      attached to Ulva and Gigartina, and Conopeum and Gigartina predominately attached
      to trochids. These "affinities" for different habitat-forming species probably
      reflect species-specific traits of juveniles and adults. Finally, manipulative
      experiments confirmed that the amount of seaweed and trochids was important and
      consistent regulators of the habitat cascade in different estuarine environments.
      We also interpreted this cascade as a habitat-formation network that describes
      the likelihood of an inhabitant being found attached to a specific habitat
      former. We conclude that the strength of the cascade increased with the amount of
      higher-order habitat-formers, with differences in form and function between
      higher and lower-order habitat-formers, and with the affinity of inhabitants for
      higher-order habitat-formers. We suggest that long habitat cascades are common
      where species traits allow for physical attachment to other species, such as in
      marine benthic systems and old forest.

PMID- 27878097
TI  - Population genetic isolation and limited connectivity in the purple finch
      (Haemorhous purpureus).
AB  - Using a combination of mitochondrial and z-linked sequences, microsatellite data,
      and spatio-geographic modeling, we examined historical and contemporary factors
      influencing the population genetic structure of the purple finch (Haemorhous
      purpureus). Mitochondrial DNA data show the presence of two distinct groups
      corresponding to the two subspecies, H. p. purpureus and H. p. californicus. The
      two subspecies likely survived in separate refugia during the last glacial
      maximum, one on the Pacific Coast and one east of the Rocky Mountains, and now
      remain distinct lineages with little evidence of gene flow between them.
      Southwestern British Columbia is a notable exception, as subspecies mixing
      between central British Columbia and Vancouver Island populations suggests a
      possible contact zone in this region. Z-linked data support two mitochondrial
      groups; however, Coastal Oregon and central British Columbia sites show evidence
      of mixing. Contemporary population structure based on microsatellite data
      identified at least six genetic clusters: three H. p. purpureus clusters, two H.
      p. californicus clusters, and one mixed cluster, which likely resulted from high
      site fidelity and isolation by distance, combined with sexual selection on
      morphological characters reinforcing subspecies differences.

PMID- 27878098
TI  - Importance of geographic origin for invasion success: A case study of the North
      and Baltic Seas versus the Great Lakes-St. Lawrence River region.
AB  - Recently, several studies indicated that species from the Ponto-Caspian region
      may be evolutionarily predisposed to become nonindigenous species (NIS); however,
      origin of NIS established in different regions has rarely been compared to
      confirm these statements. More importantly, if species from certain area/s are
      proven to be better colonizers, management strategies to control transport
      vectors coming from those areas must be more stringent, as prevention of new
      introductions is a cheaper and more effective strategy than eradication or
      control of established NIS populations. To determine whether species evolved in
      certain areas have inherent advantages over other species in colonizing new
      habitats, we explored NIS established in the North and Baltic Seas and Great
      Lakes-St. Lawrence River regions-two areas intensively studied in concern to NIS,
      highly invaded by Ponto-Caspian species and with different salinity patterns
      (marine vs. freshwater). We compared observed numbers of NIS in these two regions
      to expected numbers of NIS from major donor regions. The expected numbers were
      calculated based on the available species pool from donor regions, frequency of
      shipping transit, and an environmental match between donor and recipient regions.
      A total of 281 NIS established in the North and Baltic Seas and 188 in the Great
      Lakes-St. Lawrence River. Ponto-Caspian taxa colonized both types of habitats,
      saltwater areas of the North and Baltic Seas and freshwater of the Great Lakes
      St. Lawrence River, in much higher numbers than expected. Propagule pressure
      (i.e., number of introduced individuals or introduction effort) is of great
      importance for establishment success of NIS; however in our study, either
      shipping vector or environmental match between regions did not clarify the high
      numbers of Ponto-Caspian taxa in our study areas. Although we cannot exclude the
      influence of other transport vectors, our findings suggest that the origin of the
      species plays an important role for the predisposition of successful invaders.

PMID- 27878099
TI  - Spatial pattern of distribution of marine invertebrates within a subtidal
      community: do communities vary more among patches or plots?
AB  - Making links between ecological processes and the scales at which they operate is
      an enduring challenge of community ecology. Our understanding of ecological
      communities cannot advance if we do not distinguish larger scale processes from
      smaller ones. Variability at small spatial scales can be important because it
      carries information about biological interactions, which cannot be explained by
      environmental heterogeneity alone. Marine fouling communities are shaped by both
      the supply of larvae and competition for resources among colonizers-these two
      processes operate on distinctly different scales. Here, we demonstrate how
      fouling community structure varies with spatial scale in a temperate Australian
      environment, and we identify the spatial scale that captures the most
      variability. Community structure was quantified with both univariate (species
      richness and diversity) and multivariate (similarity in species composition)
      indices. Variation in community structure was unevenly distributed between the
      spatial scales that we examined. While variation in community structure within
      patch was usually greater than among patch, variation among patch was always
      significant. Opportunistic taxa that rely heavily on rapid colonization of free
      space spread more evenly among patches during early succession. In contrast, taxa
      that are strong adult competitors but slow colonizers spread more evenly among
      patches only during late succession. Our findings show significant patchiness can
      develop in a habitat showing no systematic environmental spatial variation, and
      this patchiness can be mediated through different biological factors at different
      spatial scales.

PMID- 27878102
TI  - Antiretroviral naive and treated patients: Discrepancies of B cell subsets during
      the natural course of human immunodeficiency virus type 1 infection.
AB  - AIM: To evaluate alterations of memory B cell subpopulations during a 48-wk
      period in human immunodeficiency virus type 1 (HIV-1) patients. METHODS: Forty
      one antiretroviral naive and 41 treated HIV-1 patients matched for age and
      duration of HIV infection were recruited. All clinical, epidemiological and
      laboratory data were recorded or measured. The different B cell subsets were
      characterized according to their surface markers: Total B cells (CD19+), memory B
      cells (CD19+CD27+, BMCs), resting BMCs (CD19+CD27+CD21high, RM), exhausted BMCs
      (CD19+CD21lowCD27-, EM), IgM memory B (CD19+CD27+IgMhigh), isotype-switched BMCs
      (CD19+CD27+IgM-, ITS) and activated BMCs (CD19+CD21low+CD27+, AM) at baseline on
      week 4 and week 48. RESULTS: Mean counts of BMCs were higher in treated patients.
      There was a marginal upward trend of IgM memory B cell proportions which differed
      significantly in the treated group (overall trend, P = 0.004). ITS BMC increased
      over time significantly in all patients. Naive patients had of lower levels of EM
      B cells compared to treated, with a downward trend, irrespectively of highly
      active antiretroviral therapy (HAART) intake. Severe impairment of EM B cells was
      recorded to both treated (P = 0.024) and naive (P = 0.023) and patients. Higher
      proportions of RM cells were noted in HAART group, which differed significantly
      on week 4th (P = 0.017) and 48th (P = 0.03). Higher levels of AM were preserved
      in HAART naive group during the whole study period (week 4: P = 0.018 and 48: P =
      0.035). HIV-RNA viremia strongly correlated with AM B cells (r = 0.54, P = 0.01)
      and moderately with RM cells (r = -0.45, P = 0.026) at baseline. CONCLUSION: HIV
      disrupts memory B cell subpopulations leading to impaired immunologic memory over
      time. BMC, RM, EM and ITS BMC were higher in patients under HAART. Activated BMCs
      (AM) were higher in patients without HAART. Viremia correlated with AM and RM.
      Significant depletion was recorded in EM B cells irrespectively of HAART intake.
      Perturbations in BMC-populations are not fully restored by antiretrovirals.

PMID- 27878100
TI  - Neurological manifestations of Zika virus infection.
AB  - Zika virus (ZIKV) is a flavivirus (Flaviviridae family) transmitted mainly by
      Aedes mosquitoes. The virus was restricted to the African continent until its
      spread to south-east Asia in the 1980's, the Micronesia in 2007, the French
      Polynesia in 2013 and, more recently in the Americas in 2015, where, up to date,
      the World Health Organization (WHO) has estimated about 3-4 million total cases
      of ZIKV infection. During outbreaks in the French Polynesia and Brazil in 2013
      and 2015, respectively, national health authorities reported potential
      neurological complications of ZIKV disease, chiefly an upsurge in Guillain-Barre
      syndrome, which coincided with ZIKV outbreaks. On the other hand, the emergence
      of ZIKV in Brazil has been associated with a striking increase in the number of
      reported cases of microcephaly in fetus and newborns, twenty times higher than in
      that reported in previous years. While investigations are currently assessing
      whether there is an actual association between neurological complications and
      ZIKV infections, the evidence was enough worrisome for WHO to declare a public
      health emergency of international concern. Here we present an updated review
      addressing what is currently known about the possible association between ZIKV
      infection and the development of severe neurological disorders.

PMID- 27878101
TI  - Regulation of Wnt/beta-catenin signaling by herpesviruses.
AB  - The Wnt/beta-catenin signaling pathway is instrumental in successful
      differentiation and proliferation of mammalian cells. It is therefore not
      surprising that the herpesvirus family has developed mechanisms to interact with
      and manipulate this pathway. Successful coexistence with the host requires that
      herpesviruses establish a lifelong infection that includes periods of latency and
      reactivation or persistence. Many herpesviruses establish latency in progenitor
      cells and viral reactivation is linked to host-cell proliferation and
      differentiation status. Importantly, Wnt/beta-catenin is tightly connected to
      stem/progenitor cell maintenance and differentiation. Numerous studies have
      linked Wnt/beta-catenin signaling to a variety of cancers, emphasizing the
      importance of Wnt/beta-catenin pathways in development, tissue homeostasis and
      disease. This review details how the alpha-, beta-, and gammaherpesviruses
      interact and manipulate the Wnt/beta-catenin pathway to promote a virus-centric
      agenda.

PMID- 27878103
TI  - Role of RNA secondary structure in emergence of compartment specific hepatitis B
      virus immune escape variants.
AB  - AIM: To investigate the role of subgenotype specific RNA secondary structure in
      the compartment specific selection of hepatitis B virus (HBV) immune escape
      mutations. METHODS: This study was based on the analysis of the specific
      observation of HBV subgenotype A1 in the serum/plasma, while subgenotype A2 with
      G145R mutation in the peripheral blood leukocytes (PBLs). Genetic variability
      found among the two subgenotypes was used for prediction and comparison of the
      full length pregenomic RNA (pgRNA) secondary structure and base pairings. RNA
      secondary structures were predicted for 37  degrees C using the Vienna RNA fold
      server, using default parameters. Visualization and detailed analysis was done
      using RNA shapes program. RESULTS: In this analysis, using similar algorithm and
      conditions, entirely different pgRNA secondary structures for subgenotype A1 and
      subgenotype A2 were predicted, suggesting different base pairing patterns within
      the two subgenotypes of genotype A, specifically, in the HBV genetic region
      encoding the major hydrophilic loop. We observed that for subgenotype A1 specific
      pgRNA, nucleotide 358U base paired with 1738A and nucleotide 587G base paired
      with 607C. However in sharp contrast, in subgenotype A2 specific pgRNA,
      nucleotide 358U was opposite to nucleotide 588G, while 587G was opposite to 359U,
      hence precluding correct base pairing and thereby lesser stability of the stem
      structure. When the nucleotides at 358U and 587G were replaced with 358C and 587A
      respectively (as observed specifically in the PBL associated A2 sequences), these
      nucleotides base paired correctly with 588G and 359U, respectively. CONCLUSION:
      The results of this study show that compartment specific mutations are associated
      with HBV subgenotype specific alterations in base pairing of the pgRNA, leading
      to compartment specific selection and preponderance of specific HBV subgenotype
      with unique mutational pattern.

PMID- 27878105
TI  - Spread of human immunodeficiency virus 1 among men who have sex with men is
      emerging as a genuine social concern and affecting the general populace - case
      reports from Eastern India.
AB  - Human immunodeficiency virus (HIV) infection among men who have sex with men
      (MSM) has increased to a drastic proportion throughout India in the last couple
      of years due to a lack of productive identification and management framework. In
      apprehension of social disgrace these men attempt to live a normal hetero
      conjugal life and, in the process, act as a bridge in spreading the virus to
      their women partners. In this case report we have highlighted two cases which
      clearly distinguished the adequacy of HIV treatment among MSM when they are
      diagnosed during early or late phases of infection. An intensive and ample
      counseling to comprehend the psychology and sexual behavior of these men was
      found to be critically important in both the cases. Our study, which is actually
      the first of its kind, recorded and documented evidence of HIV infected MSM from
      Eastern India and renders a ray of hope among this marginally isolated group to
      comprehend the challenges and health risks faced by the MSM population. It also
      provides a format for the medical practitioners here in managing and treating
      related cases.

PMID- 27878104
TI  - Geographic integration of hepatitis C virus: A global threat.
AB  - AIM: To assess hepatitis C virus (HCV) geographic integration, evaluate the
      spatial and temporal evolution of HCV worldwide and propose how to diminish its
      burden. METHODS: A literature search of published articles was performed using
      PubMed, MEDLINE and other related databases up to December 2015. A critical data
      assessment and analysis regarding the epidemiological integration of HCV was
      carried out using the meta-analysis method. RESULTS: The data indicated that HCV
      has been integrated immensely over time and through various geographical regions
      worldwide. The history of HCV goes back to 1535 but between 1935 and 1965 it
      exhibited a rapid, exponential spread. This integration is clearly seen in the
      geo-epidemiology and phylogeography of HCV. HCV integration can be mirrored
      either as intra-continental or trans-continental. Migration, drug trafficking and
      HCV co-infection, together with other potential risk factors, have acted as a
      vehicle for this integration. Evidence shows that the geographic integration of
      HCV has been important in the global and regional distribution of HCV.
      CONCLUSION: HCV geographic integration is clearly evident and this should be
      reflected in the prevention and treatment of this ongoing pandemic.

PMID- 27878108
TI  - Can Ultrasound Findings be a Good Predictor of Sperm Parameters in Patients With
      Varicocele? A Cross-Sectional Study.
AB  - BACKGROUND: Varicocele, one of the most common causes of sperm abnormalities in
      men, is the dilation of the testicular vein (the pampiniform venous plexus) by
      more than 2 mm. Ultrasonography is the primary imaging procedure for varicocele
      diagnosis. The venous diameter is evaluated using B-mode sonography, and venous
      reflux is assessed using color Doppler sonography. OBJECTIVES: In this study, we
      investigated the association of ultrasound findings with sperm parameters in
      patients with varicocele. METHODS: Ninety-nine patients with clinically diagnosed
      varicocele were included in this study, which was performed at a university
      imaging center. Patients were evaluated for pampiniform venous plexus diameter,
      venous reflux, and testicular size on both sides. Semen analysis was performed
      for all patients. The ultrasonography parameters and semen analysis data were
      compared to assess the correlations between the results. RESULTS: The semen
      analysis parameters, including semen volume and sperm morphology, count, and
      motility, significant correlations with the diameter of the varicocele vein but
      were not correlated with testes size. In addition, the patients with reflux of
      longer than 1 s and those with reflux of less than 1 s had significant
      differences in sperm parameters and varicocele size. CONCLUSIONS: Our study
      showed that ultrasonography findings can be a good predictor of sperm parameters
      in patients with varicocele.

PMID- 27878106
TI  - Multiparameter Evaluation of the Heterogeneity of Circulating Tumor Cells Using
      Integrated RNA In Situ Hybridization and Immunocytochemical Analysis.
AB  - Circulating tumor cells (CTCs) are routinely identified as cytokeratin (CK)
      positive, epithelial cell adhesion molecule (EpCAM)-positive, and CD45-negative
      and are enriched based on EpCAM. However, there are a number of methodological
      challenges regarding both isolation and characterization of these rare CTCs
      including downregulation or absence of EpCAM in a variety of solid tumors leading
      to the omission of subpopulations of CTCs, difficulties in analyzing RNA and
      protein targets in CTCs due to the rarity of these cells, and low levels of
      targets and technological limitations of visualizing the targets of interest on
      each individual cell. Building on our previous CTC research on CD45-based
      negative magnetic separation and four-color fluorescent immunocytochemical (ICC)
      staining, RNA in situ hybridization (ISH) was applied to fluorescently target
      mRNA sequences corresponding to tumor-related genes at the single CTC level.
      Multiple categories of markers are targeted including CK, human epidermal growth
      factor receptor family markers, Hedgehog pathway markers, human papillomavirus
      markers, and protein arginine methyltransferase 5. In addition, an integrated
      method of RNA ISH and fluorescent ICC staining was developed to visualize CTCs on
      both mRNA and protein levels. The robustness of the integrated co-ICC and RNA ISH
      staining was demonstrated by a series of tests on representative tumor markers of
      different categories. The integrated staining can incorporate the advantages of
      both RNA ISH and fluorescent ICC staining and provide more intense signals and
      more specific bindings. With this integrated staining methodology, distinct
      staining patterns were applied in this report to facilitate the searching and
      characterization of rare subgroups of CTCs. These results support the existence
      of diverse groups of CTCs at both protein and mRNA transcript levels and provide
      an analytical tool for the research on CTCs of rare subgroups.

PMID- 27878107
TI  - Imaging the NADH:NAD+ Homeostasis for Understanding the Metabolic Response of
      Mycobacterium to Physiologically Relevant Stresses.
AB  - The NADH:NAD+ ratio is the primary indicator of the metabolic state of bacteria.
      NAD(H) homeostasis is critical for Mycobacterium tuberculosis (Mtb) survival and
      is thus considered an important drug target, but the spatio-temporal measurements
      of NAD(H) remain a challenge. Genetically encoded fluorescent biosensors of the
      NADH:NAD+ ratios were recently described, paving the way for investigations of
      the metabolic state of pathogens during infection. Here we have adapted the
      genetically encoded biosensor Peredox for measurement of the metabolic state of
      Mtb in vitro and during infection of macrophage cells. Using Peredox, here we
      show that inhibition of the electron transport chain, disruption of the membrane
      potential and proton gradient, exposure to reactive oxygen species and treatment
      with antimycobacterial drugs led to the accumulation of NADH in mycobacterial
      cells. We have further demonstrated that Mtb residing in macrophages displays
      higher NADH:NAD+ ratios, that may indicate a metabolic stress faced by the
      intracellular Mtb. We also demonstrate that the Mtb residing in macrophages
      display a metabolic heterogeneity, which may perhaps explain the tolerance
      displayed by intracellular Mtb. Next we studied the effect of immunological
      modulation by interferon gamma on metabolism of intracellular Mtb, since
      macrophage activation is known to restrict mycobacterial growth. We observed that
      activation of resting macrophages with interferon-gamma results in higher
      NADH:NAD+ levels in resident Mtb cells. We have further demonstrated that
      exposure of Isoniazid, Bedaquiline, Rifampicin, and O-floxacin results in higher
      NADH:NAD+ ratios in the Mtb residing in macrophages. However, intracellular Mtb
      displays lower NADH:NAD+ ratio upon exposure to clofazimine. In summary, we have
      generated reporter strains capable of measuring the metabolic state of Mtb cells
      in vitro and in vivo with spatio-temporal resolution. We believe that this tool
      will facilitate further studies on mycobacterial physiology and will create new
      avenues of research for anti-tuberculosis drug discovery.

PMID- 27878109
TI  - The Effect of Aromatherapy on Anxiety in Patients.
AB  - BACKGROUND: Anxiety is the most common mental disorder in end-stage renal disease
      patients. The use of aromatherapy as a treatment for anxiety has increased
      substantially in most countries. OBJECTIVES: This study aimed to investigate the
      effect of inhaling rose water aromatherapy on anxiety in hemodialysis patients.
      METHODS: This randomized controlled clinical trial was carried out in the
      hemodialysis ward of Birjand Vali-Asr hospital on 46 patients who were randomly
      divided into control and experimental groups. The standard state-trait anxiety
      inventory of Spielberger was used to investigate the anxiety level of the
      samples. The experimental group inhaled rose water for 4 weeks, but the control
      group did not undergo any intervention. At the end of week 2 and week 4, the
      participants' anxiety was measured, and the results were statistically analyzed.
      RESULTS: Mean scores of state and trait anxiety in the experimental group before
      intervention were 47/47 +/- 7/6 and 49/56 +/- 13/8, respectively; those after
      week 4 following the intervention were reduced to 37/1 +/- 6/5 and 42/9 +/- 10/1;
      inhalation of rose water fragrance in the experimental group caused a significant
      decrease (P < 0.001) in the state and trait anxiety levels compared with controls
      (P = 0.43). CONCLUSIONS: According to the present study, rose water noticeably
      reduces the anxiety of hemodialysis patients. Therefore, inhalation of rose water
      can improve the patient's emotional and spiritual condition during hemodialysis
      treatment.

PMID- 27878110
TI  - Discontinuation of Antimicrobial Prophylaxis (AP) in Children With Spina Bifida:
      A Case Series Analysis.
AB  - BACKGROUND: Spina bifida increases the risk for urinary tract infections (UTI).
      Antimicrobial prophylaxis (AP) reduces symptomatic UTI's but selects resistant
      organisms. Measures to ensure regular and complete emptying of the bladder
      combined with treatment of constipation reduce the risk for UTI. OBJECTIVES:
      Demonstrate that close adherence to a catheterization regimen in children with
      spina bifida (Selective Treatment - ST) reduces the need for antimicrobial
      prophylaxis. METHODS: Case series analysis of pediatric spina bifida clinic
      patients where routine antimicrobial prophylaxis was replaced by clean-catch
      catheterization and daily bowel regimen (ST). Retrospective chart review of 67
      children (mean entry age: 24 months, median age: 4 months; 32 Males, 35 Females)
      enrolled between 1986 - 2004. Mean follow-up was 128.6 months (range 3 - 257
      months). Asymptomatic and symptomatic UTI incidences were noted on AP and ST
      protocols. Creatinine clearance at study entry and follow-up was calculated by
      the age appropriate method. A multivariable regression model with delta
      Glomerular Filtration Rate (GFR) as the dependent variable, independent sample t
      test and Wilcoxon rank sum were performed with SAS v. 9.2. RESULTS: The mean
      number of infections while on AP was 8.7 (95% CI 5.72, 11.68) and was 1.0 on ST
      (95% CI 0.48, 1.43). 5 infections on the AP protocol required intravenous (IV)
      antibiotics due to resistance to oral therapy, but none on ST. Comparing change
      in GFR between both protocols (AP vs. ST) found a significant difference in the
      change of GFR by treatment protocol. CONCLUSIONS: AP did not prevent UTIs and
      resulted in more resistant organisms requiring IV antibiotics. Discontinuing AP
      allowed the return of susceptibility to oral antimicrobials and significantly
      improved GFR in those children who had previously been on AP. Adherence to a
      catheterization regimen with prompt treatment of symptomatic UTI conserved renal
      function and prevented selection of resistant organisms.

PMID- 27878111
TI  - Increasing the Reliability of the Grading System for Voiding Cystourethrograms
      Using Ultrasonography: An Inter-Rater Comparison.
AB  - BACKGROUND: To assess the effectiveness of the current vesicoureteral reflux
      (VUR) grading system according to the international classification of VUR (ICVUR)
      and to evaluate whether VUR grading accuracy could be improved by renal
      ultrasonography (RU) according to the Society for Fetal Urology (SFU) grading
      system. OBJECTIVES: Therefore, this study assessed the accuracy of the current
      VCUG staging system by assessing inter-rater reliability among pediatric
      radiologists and urologists; it also evaluated whether accuracy is increased by
      RU without consensus (with respect to VCUG grading). METHODS: Four pediatric
      urologists and four pediatric radiologists independently graded 120 voiding
      cystourethrograms (VCUGs). Middle VUR grades were divided into the following
      three groups: VUR consensus grade III (group 1), VUR consensus grade IV (group
      3), and VUR non-consensus grades III and IV (group 2). All groups were compared
      with respect to hydronephrosis grade using RU. RESULTS: The intraclass
      correlation coefficient (ICC) values ranging from 0.86 to 0.89 reflected good
      reliability. The lowest agreement was associated with middle grades (III and IV).
      A marked difference in sensitivity was observed between groups 1 and 3 (35% and
      95%, respectively, P < 0.05), indexed by SFU hydronephrosis grade, suggesting
      that VCUG cases in group 2 (n = 16 at SFU 0 or 1) could be accepted as grade III,
      and SFU scores of 2, 3, or 4 could be considered grade IV. CONCLUSIONS: Inter
      rater accuracy could be improved at middle grades using renal ultrasonography
      (USG), which could promote communication between different specialists.

PMID- 27878113
TI  - Longitudinal Serum Creatinine Levels in Relation to Graft Loss Following Renal
      Transplantation: Robust Joint Modeling of Longitudinal Measurements and Survival
      Time Data.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a major public health problem that
      may lead to end-stage renal disease (ESRD). Renal transplantation has become the
      treatment modality of choice for the majority of patients with ESRD. It is
      therefore necessary to monitor the disease progression of patients who have
      undergone renal transplantation. In order to monitor the disease progression, the
      continuous assessment of kidney function over time is considered. OBJECTIVES:
      This study aimed to investigate the etiological role of recipient characteristics
      in serum creatinine changes within the follow-up period and in relation to the
      graft failure risk, as well as to evaluate whether or not the serum creatinine
      level represents an indicator of graft failure following renal transplantation.
      METHODS: This retrospective cohort study was conducted at the department of
      nephrology, Baqiyatallah Hospital, Baqiyatallah University of Medical Sciences,
      between April 2005 and December 2008. The study involved 413 renal
      transplantation patients. The primary outcomes were the determination of the
      serum creatinine levels at each attendance and the time to graft failure. Robust
      joint modeling of the longitudinal measurements (serum creatinine level) and time
      to-event data (time to graft failure) were used for the analysis in the presence
      of outliers in the serum creatinine levels. The data analysis was implemented in
      WinBUGS 1.4.3. RESULTS: There was a positive association between the serum
      creatinine level and graft failure (HR = 5.13, P < 0.001). A one unit increase in
      the serum creatinine level suggests an increased risk of graft failure of up to
      5.13 times. The serum creatinine level significantly decreased over time (95% CI:
      (-1.58, -1.08)). The recipient's age was negatively associated with the serum
      creatinine level (95% CI: (-0.02, -0.001)). CONCLUSIONS: Graft failure is more
      likely to occur in patients with higher serum creatinine levels.

PMID- 27878112
TI  - Withania coagulans Extract Induces Cell Apoptosis and Inhibits COX-2 Expression
      in a Rat Model of Benign Prostatic Hyperplasia.
AB  - BACKGROUND: Phytotherapy is a popular treatment option in cases of benign
      prostatic hyperplasia (BPH), with many different herbal products being used for
      the treatment of this condition. Withania coagulans (WC) is an herbal medicine
      that has shown anti-tumoral, anti-inflammatory, and antioxidant effects.
      OBJECTIVES: This study examined the effect of Withania coagulans extract (WCE) on
      prostatic cell apoptosis and cyclooxygenase-2 (COX-2) expression in cases of
      benign prostatic hyperplasia (BPH) in rats. METHODS: Forty Wistar rats were
      equally divided into five groups: control, sham, BPH, BPH + WCE, and BPH + CLX
      (celecoxib) as a positive control group. The induction of BPH was achieved via
      the subcutaneous injection of 3 mg/kg of testosterone propionate (TP) daily for
      28 days. The animals received WCE, celecoxib, or distilled water by oral gavage
      accompanied by the TP injection. After four weeks, the prostate glands of the
      rats were weighed to measure the prostatic index (PI). The ventral lobes of the
      prostates were dissected and processed with paraffin blocks in order to study the
      number of mast cells. A TUNEL analysis was performed to evaluate the cell
      apoptosis, while the expression of COX-2 was examined using immunohistochemistry.
      RESULTS: BPH was obvious in the ventral lobe of the prostate, and the
      administration of WCE markedly decreased the PI and the number of mast cells (P <
      0.001) in the BPH rats. Additionally, the WCE treatment induced prostatic cell
      apoptosis when compared to the BPH group. Furthermore, following the WCE
      treatment, the expression of COX-2 in the prostatic tissues was significantly
      decreased when compared to the BPH groups. CONCLUSIONS: According to the results
      of this study, WCE was effective in the treatment of BPH in rats. It may
      therefore have beneficial effects in the treatment of patients with BPH.

PMID- 27878114
TI  - Efficacy of Biofilm Removal From Hemodialysis Piping.
AB  - BACKGROUND: Central dialysate fluid delivery systems (CDDS) are used by dialysis
      centers in Japan, and although these systems are effective at delivering
      dialysate, they have a complex piping network with numerous sites where
      contamination can develop. In Japan, cleaning disinfectants have been clinically
      evaluated based on endotoxin levels and bacterial counts, but there have been no
      published studies evaluating the biofilm removal efficacy of these agents at the
      electron microscope level. OBJECTIVES: In this study, we used electron microscopy
      to evaluate the effectiveness of various cleaning disinfectants in removing
      biofilms from hemodialysis piping. METHODS: Liquid nitrogen was used to sever a
      section of dialysis piping on which a biofilm had formed during clinical use.
      Sodium hypochlorite, acetic acid, and peracetic acid were used at stock-solution
      concentrations as cleaning disinfectants. These disinfectants were tested at room
      temperature and when heated (80 degrees C). After cleaning and disinfection,
      biofilm removal from the surface of the piping was evaluated using a scanning
      electron microscope (SEM). RESULTS: Sodium hypochlorite did not show good biofilm
      removal at room temperature or when heated. Acetic acid was more effective at
      biofilm removal when heated than at room temperature. Peracetic acid was highly
      effective at biofilm removal at both room temperature and when heated.
      CONCLUSIONS: Cleaning and disinfection using a disinfectant at a high temperature
      and high concentration effectively removes biofilms from hemodialysis piping.
      However, long-term exposure to disinfectants may affect the piping material.

PMID- 27878115
TI  - Supradiaphragmatic Inferior Vena Caval Thrombectomy Without Cardiopulmonary
      Bypass: A Case Series at a Single Center.
AB  - INTRODUCTION: Inferior vena cava tumor thrombectomy in renal cell carcinoma
      patients is a challenging procedure, frequently requiring the vascular bypass
      technique for high-level thrombi with additional complications. Adopting a
      technique such as intrapericardial control in selected cases will circumvent
      these problems. Here, we present the results of our intrapericardial control
      technique during supradiaphragmatic inferior vena caval tumor thrombectomy. CASE
      PRESENTATION: The records of six patients with supradiaphragmatic tumor thrombi,
      who underwent radical nephrectomy and thrombectomy at our center with
      intrapericardial control between the years 2008 and 2015, were retrospectively
      reviewed. The patients' characteristics, intra- and postoperative data,
      histology, and follow-up records were gathered and compared. There were no
      immediate or 30-day postoperative deaths. The mean age of the patients was 61.3
      years (range 46 - 75). The total mean duration of surgery was 315 minutes and the
      mean amount of transfused red blood cells was 4.33 units during surgery and 0.8
      units in the postoperative period. The average hospitalization duration was 8
      days (range 5 - 17). Tumor stage was T3 in four patients and T4 in two, due to
      ipsilateral adrenal involvement. The mean duration of follow-up was 33.5 months.
      Only one of the patients developed recurrences, first in the tumor bed and then
      at the site of the skin incision; these were excised with no apparent
      complications. CONCLUSIONS: Radical nephrectomy and tumor thrombectomy by
      intrapericardial control without cardiopulmonary bypass and hypothermic
      circulatory arrest is a safe and effective procedure that can avoid serious intra
      and postoperative complications while providing acceptable cancer-control and
      mortality results.

PMID- 27878116
TI  - MiniJFil(r): A New Safe and Effective Stent for Well-Tolerated Repeated
      Extracorporeal Shockwave Lithotripsy or Ureteroscopy for Medium-to-Large Kidney
      Stones?
AB  - BACKGROUND: Percutaneous nephrolithotomy (PCNL) is recommended for treating
      staghorn stones or stones measuring > 20 mm. Extracorporeal shockwave lithotripsy
      (ESWL) or flexible ureteroscopy (URS) may be used as a complement. However, PCNL
      can cause trauma to the kidney parenchyma, and patients may find a noninvasive
      procedure, such as ESWL, to be more attractive. OBJECTIVES: The aim of this study
      was to evaluate the clinical efficiency of MiniJFil(r) stenting associated with
      ESWL or second-line URS for the treatment of medium-to-large kidney stones. The
      MiniJFil(r) is a stent reduced to a suture of 0.3F attached to a renal pigtail.
      The entire ureter is occupied only by the suture of the stent. METHODS: We
      retrospectively analyzed the data of 28 patients. Twenty-four patients had kidney
      stones measuring > 15 mm (group 1) and four patients had staghorn stones (group
      2). All of the patients were fitted with MiniJFil(r) 2 - 3 weeks before any
      treatment. ESWL was always our first-line therapy. Stone-free (SF) status was
      defined as no evidence of stones. RESULTS: In group 1, the mean largest and
      cumulative stone diameters, respectively, were 18.7 +/- 5.7 mm and 45.0 +/- 12.0
      mm. In group 2, the mean volume was 6,288.4 +/- 2,733.0 mm3. The overall SF was
      96.4% (100% for group 1 and 75% for group 2). The mean number of sessions of ESWL
      and URS, respectively, was 1.4 +/- 0.7 and 0.8 +/- 0.9 in group 1 and 4.0 +/- 2.0
      and 1.5 +/- 1.3 in group 2. The mean times to achieve these rates were 3.2 +/-
      1.7 months and 5.6 +/- 2.3 months for groups 1 and 2, respectively. One patient
      in group 2 was treated with only three sessions of ESWL. Renal colic was observed
      in only five patients (17.9%). CONCLUSIONS: MiniJFil(r) stenting is safe and may
      be an alternative for the treatment of kidney stones during minimally invasive
      procedures.

PMID- 27878117
TI  - GPC-3 in hepatocellular carcinoma: current perspectives.
AB  - Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, attaches to the
      cell membrane and is frequently observed to be elevated in hepatocellular
      carcinoma (HCC). However, GPC3 is not detected in normal liver tissues and benign
      liver lesions. Consequently, GPC3 is currently being used as a diagnostic
      biomarker and HCC-specific positron emission computed tomography probe to
      identify HCCs in normal liver tissues and benign liver lesions. The
      overexpression of GPC-3 in serum or liver tissue also predicts poor prognosis for
      HCC patients. In addition, GPC3 promotes HCC growth and metastasis by activating
      the canonical Wnt and other signaling pathways. Targeting of GPC3, including
      GC33, HN3 and YP7, might offer new immunotherapeutic tools for HCC treatment.

PMID- 27878118
TI  - Cancer-Related Functions and Subcellular Localizations of Septins.
AB  - Since the initial discovery of septin family GTPases, the understanding of their
      molecular organization and cellular roles keeps being refined. Septins have been
      involved in many physiological processes and the misregulation of specific septin
      gene expression has been implicated in diverse human pathologies, including
      neurological disorders and cancer. In this minireview, we focus on the importance
      of the subunit composition and subcellular localization of septins relevant to
      tumor initiation, progression, and metastasis. We especially underline the
      importance of septin polymer composition and of their association with the plasma
      membrane, actin, or microtubules in cell functions involved in cancer and in
      resistance to cancer therapies. Through their scaffolding role, their function in
      membrane compartmentalization or through their protective function against
      protein degradation, septins also emerge as critical organizers of membrane
      associated proteins and of signaling pathways implicated in cancer-associated
      angiogenesis, apoptosis, polarity, migration, proliferation, and in metastasis.
      Also, the question as to which of the free monomers, hetero-oligomers, or
      filaments is the functional form of mammalian septins is raised and the control
      over their spatial and temporal localization is discussed. The increasing amount
      of crosstalks identified between septins and cellular signaling mediators
      reinforces the exciting possibility that septins could be new targets in anti
      cancer therapies or in therapeutic strategies to limit drug resistance.

PMID- 27878121
TI  - Corrigendum: Designer Leptin Receptor Antagonist Allo-aca Inhibits VEGF Effects
      in Ophthalmic Neoangiogenesis Models.
AB  - [This corrects the article on p. 67 in vol. 3, PMID: 27790618.].

PMID- 27878122
TI  - Europe on Fire; Medical Management of Terror Attacks - New Era and New
      considerations.

PMID- 27878119
TI  - The Role of microRNA Markers in the Diagnosis, Treatment, and Outcome Prediction
      of Spinal Cord Injury.
AB  - Spinal cord injury (SCI) is a devastating condition that affects many people
      worldwide. Treatment focuses on controlling secondary injury cascade and
      improving regeneration. It has recently been suggested that both the secondary
      injury cascade and the regenerative process are heavily regulated by microRNAs
      (miRNAs). The measurement of specific biomarkers could improve our understanding
      of the disease processes, and thereby provide clinicians with the opportunity to
      guide treatment and predict clinical outcomes after SCI. A variety of miRNAs
      exhibit important roles in processes of inflammation, cell death, and
      regeneration. These miRNAs can be used as diagnostic tools for predicting outcome
      after SCI. In addition, miRNAs can be used in the treatment of SCI and its
      symptoms. Significant laboratory and clinical evidence exist to show that miRNAs
      could be used as robust diagnostic and therapeutic tools for the treatment of
      patients with SCI. Further clinical studies are warranted to clarify the
      importance of each subtype of miRNA in SCI management.

PMID- 27878120
TI  - Advances in Stem Cell Research- A Ray of Hope in Better Diagnosis and Prognosis
      in Neurodegenerative Diseases.
AB  - Neurodegeneration and neurodegenerative disorders have been a global health issue
      affecting the aging population worldwide. Recent advances in stem cell biology
      have changed the current face of neurodegenerative disease modeling, diagnosis,
      and transplantation therapeutics. Stem cells also serve the purpose of a simple
      in-vitro tool for screening therapeutic drugs and chemicals. We present the
      application of stem cells and induced pluripotent stem cells (iPSCs) in the field
      of neurodegeneration and address the issues of diagnosis, modeling, and
      therapeutic transplantation strategies for the most prevalent neurodegenerative
      disorders. We have discussed the progress made in the last decade and have
      largely focused on the various applications of stem cells in the
      neurodegenerative research arena.

PMID- 27878123
TI  - Two Validated Ways of Improving the Ability of Decision-Making in Emergencies;
      Results from a Literature Review.
AB  - The aim of the current review wasto study the existing knowledge about decision
      making and to identify and describe validated training tools.A comprehensive
      literature review was conducted by using the following keywords: decision-making,
      emergencies, disasters, crisis management, training, exercises, simulation,
      validated, real-time, command and control, communication, collaboration, and
      multi-disciplinary in combination or as an isolated word. Two validated training
      systems developed in Sweden, 3 level collaboration (3LC) and MacSim, were
      identified and studied in light of the literature review in order to identify how
      decision-making can be trained. The training models fulfilled six of the eight
      identified characteristics of training for decision-making.Based on the results,
      these training models contained methods suitable to train for decision-making.

PMID- 27878125
TI  - Increased Likelihood of Arrhythmic Events Associated with Increased Anxiety in
      Patients with Implanted Cardiac Defibrillators after the Ahar-Varzegan Earthquake
      in East Azarbaijan, 2012.
AB  - OBJECTIVE: To determine the type and pattern of arrhythmic events following the
      2012 Ahar-Varzegan Earthquake among patients implanted with cardiac
      defibrillators (ICDs) in East Azarbaijan province. METHODS: In a prospective
      cohort study, conducted in East Azerbaijan Province of Iran, 132 patients were
      enrolled in two comparison groups according to the region of residence i.e.,
      earthquake region (n= 98) and non-earthquake (n= 34) region in 2012. Data were
      collected for those meeting standard criteria for sustained ventricular
      arrhythmias (VAs), or supraventricular tachycardias (SVTs) and triggered ICD
      therapies, either shock or anti-tachycardia pacing (ATP). The state version of
      the State-Trait Anxiety Inventory (STAI-S) was used to assess general symptoms of
      anxiety in both groups. RESULTS: Males comprised 81.1% of the participants. Mean
      age of the participants was 59.7 +/-15 years. The frequency of patients with
      sustained VAs increased significantly after the earthquake (p=0.008).  There were
      more VAs (mean 2.16 vs. 6.23; p=0.008) and they occurred earlier (6th vs. 16th
      day; p= 0.01) in the earthquake area. The mean frequency of SVTs and the total
      number of delivered ICD therapies were similar between groups. Differences in
      anxiety levels were not significant between groups but there was a trend for
      presence of greater number of patients with anxiety (p=0.07) and the relative
      severity of anxiety (p=0.08) in the earthquake area. CONCLUSION:  In the
      earthquake area, the mean frequency of VAs increased and they occurred earlier in
      the earthquake area. The stress of anxiety might have served as a trigger for
      these events.

PMID- 27878124
TI  - Ultra-Early versus Early Excision and Grafting for Thermal Burns up to 60% Total
      Body Surface Area; A Historical Cohort Study.
AB  - OBJECTIVE: To compare the outcome of patients with up to 60% total body surface
      area (TBSA) thermal burns undergoing ultra-early and early excision and grafting.
      METHODS: This historical cohort study was performed in two referral burn centers
      of Shiraz during a 1-year period from 2015 to 2016. We included those patients
      with thermal burns up to 60% TBSA who underwent ultra-early (48-72 hours) and
      early (7-10 days) excision and grafting. We excluded those who were
      hemodynamically unstable and those with electrical burns. The outcome of patients
      was determined by graft success, operation duration, blood loss, hospital length
      of stay and mortality rate. RESULTS: We included a total number of 107 patients
      with mean age of 32.1 +/- 11.6 years. There were 65 (60.7%) men and 42 (39.3%)
      women among the patients. Both study groups were comparable regarding the
      baseline characteristics. Ultra-early excision and grafting was associated with
      more, higher graft success rate (p=0.048), lower infection rate (p=0.037),
      shorter hospital length of stay (p=0.044) and lower mortality rate (p=0.027).
      CONCLUSION: Ultra-early excision and grafting in patients with thermal burns
      covering less than 60% TBSA was associated with higher graft success rate,
      shorter hospital length of stay, lower infection rate and lower mortality rate
      when compared to early surgery.

PMID- 27878126
TI  - Validity of the Electronic Triage System in Predicting Patient Outcomes in
      Tabriz, Iran: A Cross-Sectional Study.
AB  - OBJECTIVE: To validate the triage ratings performed by the Electronic Triage
      System (ETS) using hospitalization, length of stay, resource use, in-hospital
      mortality and patient bills as outcome measures. METHODS: In this retrospective
      cross-sectional study the medical records of 387 patients were reviewed in a one
      week period. The data included triage category and the outcome measures were
      hospitalization, length of stay, in-hospital mortality, patient bill, and used
      resources. The association between the triage category and hospitalization and
      death was assessed. The association between the triage category and the number of
      resources, length of stay, and the bill was also assessed. RESULTS: The mean age
      of the patients was 43.65 +/-21.17 years. Women comprised 40% (n=155) of 387
      people who were included in the study. The frequency of Emergency Severity Index
      (ESI) 1, 2, 3, 4 and 5 categories were 18, 61, 127, 181 and 0 respectively. Phi
      and Cramer's V for hospitalization and death were 0.365 (p<0.001) and 0.305
      (p<0.001). Spearman's rho for bill, length of stay, and resource use were -0.483
      (p<0.001), -0.228 (p<0.001) and -0.490 (p<0.001). The association between triage
      category and resource consumption was stronger than other outcomes. CONCLUSION:
      The ETS was valid in predicting all studied patient outcomes. The ETS has also
      the advantages of providing quick reports, giving feedback and providing data for
      research purposes.

PMID- 27878127
TI  - The Burden of Road Traffic Injuries in Yazd Province - Iran.
AB  - OBJECTIVES: To estimate the Disabled-adjusted Life Years (DALYs) of Road Traffic
      Accidents in patients referred to hospitals in Yazd Province, central Iran.
      METHODS: This cross-sectional study was conducted in Yazd province during 2010.
      To calculate the Years of Life Lost (YLL) due to premature death and to calculate
      the incidence of non-fatal injuries and Years Lost due to Disability (YLD), the
      data were collected from Yazd death registration system and hospital records. The
      causes of death and nature of non-fatal injuries were classified using
      International Classification of Diseases (ICD-10). We estimated Disability
      Adjusted Life Years (DALYs) on the guidelines of the Global Burden of Disease
      Study (discount rate: 0.03, age weight: 0.04, constant age weight correction
      factor: 0.165). Age and sex composition was taken from the National Statistical
      Center for the year 2010. RESULTS: During 2009, 483 deaths were caused by traffic
      accidents in Yazd Province, 382 (79.09%) of which were males, and 101 (20.91%)
      were females. The mortality rates for males and females were 70.98 and 20.15 in
      100,000, respectively. The years of life lost due to premature deaths were
      15.84/1000 in men and 4.75/1,000 in women. Total YLLs caused by traffic accidents
      were 10,908 years. The injuries caused by traffic accidents were calculated as
      15.21 and 3.73/1,000 in males and females, respectively. The total YLDs was
      calculated 1.51/1,000. The total burden of Road Traffic Injuries in Yazd province
      was 12478 years (DALYs), 87.41% of which was due to premature death, and 12.59%
      was related to disability. Also, 78.32% was lost in males. The age specific peak
      of burden was in 15-29 year. CONCLUSION: This study showed that traffic accidents
      in Yazd impose a high burden. It seems that it is one of the health sector
      priorities. It is recommended to revise laws on use of motorcycles, especially on
      helmet use for motorcyclists, enforce strict laws in residential areas, and
      review social determinant affecting the incidence of such accidents.

PMID- 27878128
TI  - The Epidemilogical Characteristics of Motorcyclists Associated Injuries in Road
      Traffics Accidents; A Hospital-Based Study.
AB  - OBJECTIVES: To determine the epidemiology of injuries of the motorcyclists in
      road traffic accidents (RTIs) between 2008 and 2014 in East Azarbayejan province
      of Iran. METHODS: A cross-sectional study was performed in East Azerbaijan
      province in Imam Reza hospital on motorcyclists subjected to injuries in RTIs
      between 2008 and 2014. Demographic characteristics (age, sex), duration of
      hospitalization, final status of injured people after discharge from the
      hospital, admission ward, number of admissions due to injuries in RTIs, nature of
      injury, and the clinical services provided to injured people were gathered from
      hospital information system (HIS). Demographic characteristics (age, sex),
      duration of hospitalization, final status of injured people after discharge from
      the hospital, admission ward, number of admissions due to injuries in RTIs,
      injured site of the body, nature of injury, and the clinical services provided
      injured people were gathered from HIS. Standardized data collection form was used
      for uniform handling of the data. RESULTS: Most of the victims (94.4%) were male.
      The most frequent injuries pertained to the age group of 18-30 with 1676 (51.4%)
      injuries. Head, abdomen, lower back, lumbar spine, and pelvis, were the most
      common injured sites, respectively. Reduction of fracture and dislocation and
      cranial puncture were the most common provided services. The lowest survival time
      belonged to the age group over 60 years old. CONCLUSION: Injuries to the head are
      the most prevalent injuries among motorcyclists in RTIs. So it is suggested that
      proper interventions be implemented to ensure wearing helmet by motorcyclist and
      pillion passengers.

PMID- 27878129
TI  - An Epidemiological Study of Road Traffic Accidents in Guilan Province, Northern
      Iran in 2012.
AB  - OBJECTIVE: To determine the epidemiological characteristics of the road traffic
      injuries (RTIs) in Guilan province, northern Iran. METHODS: This study was a
      cross-sectional study which included all of RTIs admitted to medical centers of
      Guilan province (northern Iran) during 2012. ICD-10 was used as diagnostic
      criteria. Demographic variables also injury circumstance and in hospital
      variables such as length of stay, time of admission, type of surgery, ICU
      admission, final outcome and mechanism of injury, anatomical part of injury
      according to Abbreviated Injury Scale (AIS) classification were derives from
      records by trained research team. Descriptive data is reported. The predictors of
      mortality were also determined. RESULTS: The prevalence of road traffic injuries
      in Guilan province was 31 in 10,000 populations. Of total 7671 accidents, 5976
      (77.9%) were men and 1695 (22.1%) were women. Mean age of these victims was 33.3
      +/- 17.289 years (32.64+/-16.939 for men, 35.62+/-18.312 for women). Most of them
      (32.5%) were 20-29 years old. Motorcycle-car accidents had the highest frequency
      followed by car-car crashes and car accidents involving pedestrians. Most of the
      patients (85.9%) were hospitalized and 280 injured died (3.7%). Upper extremities
      were the most sites of injuries. Male sex, length of hospital stay, multiple
      injuries and increased age were associated with road traffic accident associated
      mortality. CONCLUSION: RTIs cause enormous death and disability in this area and
      more road traffic preventive programs should be enforcement in these areas to
      reduce incidences RTI.

PMID- 27878130
TI  - An Unusual Case of Transorificial Abdomino-Thoracic Impalement Injury in a Child.
AB  - Impalement injuries are rare in the paediatric age group. Still rarer are
      injuries which traverse multiple body cavities. Such injuries require
      multispecialty management at a tertiary care centre. We describe a case of an
      accidental impalement injury in a 12-year-old boy after a fall from height. The
      rod was seen passing through the right lung in the paracardiac region, piercing
      the diaphragm and segment IV of the liver and then coursing anterior to the
      inferior vena cava in the midline. It was seen passing through the small bowel at
      multiple places and then coursing behind the bladder, entering the rectum and
      anal canal. Intra-operatively, right intercostal chest drain was inserted. At
      laparotomy, the liver was mobilized and a diaphragmatic tear of 2*1cm was
      visualized. The rod traversed through the right lobe of liver with no active
      bleeding. Both the entry and exit sites through the liver were visualized. The
      rod was also seen passing through the small bowel and its mesentery. The rod
      entered the pelvis posterior to the bladder below the peritoneal reflection.
      Moderate hemoperitoneum and fecal contamination was present. The rod was
      successfully removed and the patient was discharged with good condition and was
      well on follow up.

PMID- 27878131
TI  - Extra Luminal Entrapment of Guide Wire; A Rare Complication of Central Venous
      Catheter Placement in Right Internal Jugular Vein.
AB  - Central venous Catheterization (CVC) is a commonly performed procedure for venous
      access. It is associated with several complications. We report a rare case of
      extra luminal entrapment of guide wire during CVC placement in right jugular
      vein. We report a case of 28 years old female patient presented in our emergency
      with history of entrapped guide wire in right side of neck during CVC. X-ray
      showed coiling of guide wire in neck. CT Angiography showed guide wire coursing
      in between common carotid artery and internal jugular vein (IJV), closely
      abutting the wall of both vessels. The guide wire was coiled with end coursing
      behind the esophageal wall. Guide wire was removed under fluoroscopic guide
      manipulation under local anesthesia. We want to emphasize that even though CVC
      placement is common and simple procedure, serious complication can occur in hands
      of untrained operator. The procedure should be performed under supervision, if
      done by trainee. Force should never be applied to advance the guide wire if
      resistance is encountered.

PMID- 27878133
TI  - Massive Pneumocephalus and Pneumorrhachis after Severe Skull Base Fracture.

PMID- 27878132
TI  - Ruptured Cystic Mesothelioma Diagnosed after Blunt Trauma; Case Report and
      Literature Review.
AB  - The majority of blunt trauma is secondary to motor vehicle crashes,especially in
      those wearing seatbelts or sitting in the front or passenger seat location.Hollow
      viscus gastrointestinal injuries occur more frequently in small bowel, followed
      by colorectal, duodenum, stomach and appendix. A 25-year-old male presents after
      being involved in a motor vehicle accident. Initialworkup was significant for
      moderate amount of pelvic free fluid and curvilinear,cysticlike structures in the
      pelvis. He subsequently developed peritonitis and underwentdiagnostic
      laparoscopy, which revealed multiple cystic nodules arising from theperitoneum.
      Pathology demonstrated benign cystic mesothelioma (BCM). BCM is a very
      rarecondition of mesotheliallined, variably sized, fluidfilled cysts that arises
      from theserous, pericardial or peritoneal lining. Due to the scarcity of cases,
      its management and prognosis are not fully established. This singular case
      highlights the necessity for a clinician to have a widedifferential forunusual
      causes of free pelvic fluid after blunt abdominaltrauma.

PMID- 27878134
TI  - Pneumopericardium.

PMID- 27878136
TI  - Phenotypic convergence of Menkes and Wilson disease.
AB  - Menkes disease is an X-linked multisystem disorder with epilepsy, kinky hair, and
      neurodegeneration caused by mutations in the copper transporter ATP7A. Other
      ATP7A mutations have been linked to juvenile occipital horn syndrome and adult
      onset hereditary motor neuropathy.1,2 About 5%-10% of the patients present with
      "atypical Menkes disease" characterized by longer survival, cerebellar ataxia,
      and developmental delay.2 The intracellular copper transport is regulated by 2 P
      type ATPase copper transporters ATP7A and ATP7B. These proteins are expressed in
      the trans-Golgi network that guides copper to intracellular compartments, and in
      copper excess, it relocates copper to the plasma membrane to pump it out from the
      cells.3ATP7B mutations cause Wilson disease with dystonia, ataxia, tremor, and
      abnormal copper accumulation in the brain, liver, and other organs.4.

PMID- 27878137
TI  - Mitochondrial cytopathy with common MELAS mutation presenting as multiple system
      atrophy mimic.
AB  - Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS) syndrome1 is one of the most frequently inherited mitochondrial
      disorders. MELAS syndrome is a systemic disease with multiple organ involvement.2
      The most common mutation in MELAS is the m.3243A>G mutation in the MT-TL1 gene.2.

PMID- 27878135
TI  - Control of the heart rate of rat embryos during the organogenic period.
AB  - The aim of this study was to gain insight into whether the first trimester embryo
      could control its own heart rate (HR) in response to hypoxia. The gestational day
      13 rat embryo is a good model for the human embryo at 5-6 weeks gestation, as the
      heart is comparable in development and, like the human embryo, has no functional
      autonomic nerve supply at this stage. Utilizing a whole-embryo culture technique,
      we examined the effects of different pharmacological agents on HR under normoxic
      (95% oxygen) and hypoxic (20% oxygen) conditions. Oxygen concentrations <=60%
      caused a concentration-dependent decrease in HR from normal levels of ~210 bpm.
      An adenosine agonist, AMP-activated protein kinase (AMPK) activator and KATP
      channel opener all caused bradycardia in normoxic conditions; however, putative
      antagonists for these systems failed to prevent or ameliorate hypoxia-induced
      bradycardia. This suggests that the activation of one or more of these systems is
      not the primary cause of the observed hypoxia-induced bradycardia. Inhibition of
      oxidative phosphorylation also decreased HR in normoxic conditions, highlighting
      the importance of ATP levels. The beta-blocker metoprolol caused a concentration
      dependent reduction in HR supporting reports that beta1-adrenergic receptors are
      present in the early rat embryonic heart. The cAMP inducer colforsin induced a
      positive chronotropic effect in both normoxic and hypoxic conditions. Overall,
      the embryonic HR at this stage of development is responsive to the level of
      oxygenation, probably as a consequence of its influence on ATP production.

PMID- 27878138
TI  - Measuring Process Dynamics and Nuclear Migration for Clones of Neural Progenitor
      Cells.
AB  - Neural stem and progenitor cells (NPCs) generate processes that extend from the
      cell body in a dynamic manner. The NPC nucleus migrates along these processes
      with patterns believed to be tightly coupled to mechanisms of cell cycle
      regulation and cell fate determination. Here, we describe a new segmentation and
      tracking approach that allows NPC processes and nuclei to be reliably tracked
      across multiple rounds of cell division in phase-contrast microscopy images.
      Results are presented for mouse adult and embryonic NPCs from hundreds of clones,
      or lineage trees, containing tens of thousands of cells and millions of
      segmentations. New visualization approaches allow the NPC nuclear and process
      features to be effectively visualized for an entire clone. Significant
      differences in process and nuclear dynamics were found among type A and type C
      adult NPCs, and also between embryonic NPCs cultured from the anterior and
      posterior cerebral cortex.

PMID- 27878140
TI  - Contributions of the Hfq protein to translation regulation by small noncoding
      RNAs binding to the mRNA coding sequence.
AB  - The bacterial Sm-like protein Hfq affects the regulation of translation by small
      noncoding RNAs (sRNAs). In this way, Hfq participates in the cell adaptation to
      environmental stress, regulation of cellular metabolism, and bacterial virulence.
      The majority of known sRNAs bind complementary sequences in the 5'-untranslated
      mRNA regions. However, recent studies have shown that sRNAs can also target the
      mRNA coding sequence, even far downstream of the AUG start codon. In this review,
      we discuss how Hfq contributes to the translation regulation by those sRNAs which
      bind to the mRNA coding sequence.

PMID- 27878139
TI  - Compound heterozygous LDLR variant in severely affected familial
      hypercholesterolemia patient.
AB  - Familial hypercholesterolemia (FH) is most commonly caused by mutations in the
      LDL receptor (LDLR), which is responsible for hepatic clearance of LDL from the
      blood circulation. We described a severely affected FH proband and their first
      degree blood relatives; the proband was resistant to statin therapy and was
      managed on an LDL apheresis program. In order to find the causative genetic
      variant in this family, direct exon sequencing of the LDLR, APOB and PCSK9 genes
      was performed. We identified a compound heterozygous mutation in the proband with
      missense p.(W577C) and frameshift p.(G676Afs33) variants at exons 12 and 14 of
      the LDLR gene respectively. DNA sequencing of LDLR gene from the parents
      demonstrated that the missense variant was inherited from the mother and
      frameshift variant was inherited from the father. The frameshift variant resulted
      in a stop signal 33 codons downstream of the deletion, which most likely led to a
      truncated protein that lacks important functional domains, including the trans
      membrane domain and the cytoplasmic tail domain. The missense variant is also
      predicted to be likely pathogenic and affect EGF-precursor homology domain of the
      LDLR protein. The segregation pattern of the variants was consistent with the
      lipid profile, suggesting a more severe FH phenotype when the variants are in the
      compound heterozygous state. The finding of a compound heterozygous mutation
      causing severe FH phenotype is important for the genotype-phenotype correlation
      and also enlarges the spectrum of FH-causative LDLR variants in the Arab
      population, including the Saudi population.

PMID- 27878142
TI  - MicroRNA biogenesis: Epigenetic modifications as another layer of complexity in
      the microRNA expression regulation.
AB  - Since their discovery, microRNAs have led to a huge shift in our understanding of
      the regulation of key biological processes. The discovery of epigenetic
      modifications that affect microRNA expression has added another layer of
      complexity to the already tightly controlled regulatory machinery. Modifications
      like uridylation, adenylation and RNA editing have been shown to have variable
      effects on miRNA biogenesis and action. Methylation of the N6 adenosine has been
      studied extensively in mRNA. Presence of the N6-methyl-adenosine (m6A) mark and
      its critical importance in miRNA biogenesis in animals adds to our understanding
      of the regulatory mechanisms, while its effect on miRNA biogenesis in plants is
      yet to be understood.

PMID- 27878141
TI  - Assessing the 5S ribosomal RNA heterogeneity in Arabidopsis thaliana using short
      RNA next generation sequencing data.
AB  - In eukaryotes, ribosomal 5S rRNAs are products of multigene families organized
      within clusters of tandemly repeated units. Accumulation of genomic data obtained
      from a variety of organisms demonstrated that the potential 5S rRNA coding
      sequences show a large number of variants, often incompatible with folding into a
      correct secondary structure. Here, we present results of an analysis of a large
      set of short RNA sequences generated by the next generation sequencing
      techniques, to address the problem of heterogeneity of the 5S rRNA transcripts in
      Arabidopsis and identification of potentially functional rRNA-derived fragments.

PMID- 27878143
TI  - Membrane-less organic-inorganic aqueous flow batteries with improved cell
      potential.
AB  - A membrane-less organic-inorganic flow battery based on zinc and quinone species
      is proposed. By virtue of the slow dissolution rate of the deposited anode (<11.5
      mg h-1 cm-2), the battery has a cell voltage of ca. 1.52 V with an average energy
      efficiency of ca. 73% at 30 mA cm-2 over 12 cycles.

PMID- 27878144
TI  - Characteristics of chemical bonding of pentavalent uranium in La-doped UO2.
AB  - The effect of La doping on the electronic structure of U in UO2 was studied using
      an advanced technique, namely, X-ray absorption spectroscopy (XAS) in the high
      energy-resolution fluorescence-detection (HERFD) mode, at the U 3d3/2 (M4) edge.
      Thanks to a significant reduction of the core-hole lifetime broadening and
      distinct chemical shifts of the HERFD-XAS lines, the U(v) formation as a result
      of La doping was identified. The isolated contribution of U(v) in the M4 HERFD
      XAS spectrum reveals the so-called charge-transfer satellites due to the U 5f-O
      2p hybridization. The analysis of the experimental data within the framework of
      the Anderson impurity model (AIM) indicates a significant change in the
      characteristics and degree of covalency for the chemical bonding in the U(v)
      subsystem of UO2 as compared to undoped UO2, which is a Mott-Hubbard system. The
      results are also supported by AIM calculations of X-ray photoelectron and optical
      absorption data.

PMID- 27878145
TI  - Chiral nanoscale pores created during the surface explosion of tartaric acid on
      Cu(111).
AB  - The autocatalytic decomposition of tartaric acid on Cu(111) exhibits unique
      kinetics, which are linked to a hexagonal surface structure adopted at high
      coverage. The chirality imposed on the surface by tartaric acid throughout the
      explosion process is presented, and the hexagonal structure shows promise as a
      chiral template for enantiospecific surface chemistry.

PMID- 27878146
TI  - Acoustofluidic particle trapping, manipulation, and release using dynamic-mode
      cantilever sensors.
AB  - We show here that dynamic-mode cantilever sensors enable acoustofluidic fluid
      mixing and trapping of suspended particles as well as the rapid manipulation and
      release of trapped micro-particles via mode switching in liquid. Resonant modes
      of piezoelectric cantilever sensors over the 0 to 8 MHz frequency range are
      investigated. Sensor impedance response, flow visualization studies using dye and
      micro-particle tracers (100 MUm diameter), and finite element simulations of
      cantilever modal mechanics and acoustic streaming show fluid mixing and particle
      trapping configurations depend on the resonant mode shape. We found trapped
      particles could be: (1) rapidly manipulated on millimeter length scales, and (2)
      released from the cantilever surface after trapping by switching between low- and
      high-order resonant modes (less than 250 kHz and greater than 1 MHz,
      respectively). Such results suggest a potentially promising future for dynamic
      mode cantilevers in separations, pumping and mixing applications as well as
      acoustofluidic-enhanced sensing applications.

PMID- 27878147
TI  - Highly efficient reduction of carbon dioxide with a borane catalyzed by
      bis(phosphinite) pincer ligated palladium thiolate complexes.
AB  - Highly efficient catalytic reduction of CO2 with catecholborane has been
      developed by using bis(phosphinite) pincer ligated palladium thiolate complexes.
      Turnover frequencies up to 1780 h-1 have been achieved at room temperature under
      an atmospheric pressure of CO2. These thiolate complexes represent the most
      efficient homogeneous catalysts known to date for the reduction of CO2 to
      methanol under mild conditions.

PMID- 27878148
TI  - Photo/chemo dual-controlled reversible morphological conversion and chiral
      modulation of supramolecular nanohelixes with nanosquares and nanofibers.
AB  - A photo/chemo dually interconvertible system was constructed through the
      supramolecular assembly of azobenzene-diphenylalanine (Azo-FF) with alpha
      cyclodextrin. The resultant chiral nanohelix was able to interconvert into a
      nanosquare upon irradiation at different wavelengths, but into a nanofiber upon
      changing solvent polarity, which provides a feasible way to achieve highly
      ordered nanostructures with various morphologies, dimensions and chiralities.

PMID- 27878150
TI  - Controllable selenium vacancy engineering in basal planes of mechanically
      exfoliated WSe2 monolayer nanosheets for efficient electrocatalytic hydrogen
      evolution.
AB  - Engineering intrinsic selenium vacancies (Se-vacancies) was achieved in
      mechanically exfoliated WSe2 monolayer nanosheets (WSe2 MLNSs) via an annealing
      treatment. Our theoretical and experimental results reveal that these Se
      vacancies can efficiently activate and optimize the basal planes of the WSe2
      MLNSs. As expected, the optimized catalyst exhibits efficient electrocatalytic
      hydrogen evolution.

PMID- 27878149
TI  - Synthesis of precipitating chromogenic/fluorogenic beta-glucosidase/beta
      galactosidase substrates by a new method and their application in the visual
      detection of foodborne pathogenic bacteria.
AB  - We developed a new efficient method for the synthesis of important indoxyl
      glycoside substrates for beta-glucosidase and beta-galactosidase by using 1
      acetylindol-3-ones as intermediates. This method was used to synthesise novel
      precipitating fluorogenic substrates for beta-glucosidase based on 2
      (benzothiazol-2'-yl)-phenols. We also assessed the application of these
      substrates in the detection of foodborne pathogenic bacteria.

PMID- 27878151
TI  - Formation of large nanodomains in liquid solutions near the phase boundary.
AB  - We discovered that large nanodomains were formed in liquid solutions near the
      phase boundary, and their size increased dramatically as the composition of
      solutions approached the phase boundary. Different mesoporous materials were
      synthesized using nanodomains as templates, and the pore size could be controlled
      simply by the composition of solutions.

PMID- 27878152
TI  - A heptanuclear light-harvesting metal-based antenna dendrimer with six Ru(ii)
      based chromophores directly powering a single Os(ii)-based energy trap.
AB  - The novel dendritic-shaped, heptanuclear compound 1 - the first mixed Os-Ru
      dendrimer with tris-chelating bridging ligands - has been synthesized and its
      photophysics studied by fs pump-probe transient spectroscopy. In 1, all light
      energy absorbed by six identical Ru(ii) chromophores is funnelled to the
      luminescent central Os(ii) core, with a time constant of 11 ps, by Dexter energy
      transfer.

PMID- 27878153
TI  - Effect of graphene support on large Pt nanoparticles.
AB  - State-of-the-art catalysts are often created via deposition of monolayers, sub
      monolayers or nanoparticles of the catalytic material over supports, aiming to
      increase the surface area and decrease the loading of the catalytic material and
      therefore the overall cost. Here, we employ large-scale DFT calculations to
      simulate platinum clusters with up to 309 atoms interacting with single layer
      graphene supports with up to 880 carbon atoms. We compute the adsorption,
      cohesion and formation energies of two and three-dimensional Pt clusters
      interacting with the support, including dispersion interactions via a semi
      empirical dispersion correction and a vdW functional. We find that three
      dimensional Pt clusters are more stable than the two-dimensional when interacting
      with the support, and that the difference between their stabilities increases
      with the system size. Also, the dispersion interactions are more pronounced as we
      increase the nanoparticle size, being essential to a reliable description of
      larger systems. We observe inter-atomic expansion (contraction) on the closest
      (farthest) Pt facets from the graphene sheet and charge redistribution with
      overall charge being transferred from the platinum clusters to the support. The
      Pt-Pt expansion, which is related to the charge transfer in the system,
      correlates with the adsorption energy per Pt atom in contact with the graphene.
      These, and other electronic and structural observations show that the effect of
      the support cannot be neglected. Our study provides for the first time, to the
      best of our knowledge, quantitative results on the non-trivial combination of
      size and support effects for nanoparticles sizes which are relevant to catalyst
      design.

PMID- 27878154
TI  - Ni-catalyzed reductive coupling of alpha-halocarbonyl derivatives with vinyl
      bromides.
AB  - This work describes the vinylation of alpha-halo carbonyl compounds with vinyl
      bromides under Ni-catalyzed reductive coupling conditions. While aryl-conjugated
      vinyl bromides entail pyridine as the sole labile ligand, the alkyl-substituted
      vinyl bromides require both bipyridine and pyridine as the co-ligands.

PMID- 27878155
TI  - Spin-labelled diketopiperazines and peptide-peptoid chimera by Ugi-multi
      component-reactions.
AB  - For the first time, spin-labelled coumpounds have been obtained by isonitrile
      based multi component reactions (IMCRs). The typical IMCR Ugi-protocols offer a
      simple experimental setup allowing structural variety by which labelled
      diketopiperazines (DKPs) and peptide-peptoid chimera have been synthesized. The
      reaction keeps the paramagnetic spin label intact and offers a simple and
      versatile route to a large variety of new and chemically diverse spin labels.

PMID- 27878156
TI  - Synergy between experimental and computational studies of aromatic stacking
      interactions.
AB  - Aromatic stacking interactions are one of the most common types of non-covalent
      interactions. However, their fundamental origins and the ability to accurately
      predict their stability trends are still an active area of research. The study of
      aromatic stacking interactions has been particularly challenging. The interaction
      involves a delicate balance of multiple forces, and the aromatic surfaces can
      readily adopt different interaction geometries. Thus, the collaborative efforts
      of theoretical and experimental researchers have been essential to understand and
      build more accurate predictive models of aromatic stacking interactions.

PMID- 27878158
TI  - Photo-induced phosphate released from organic phosphorus degradation in deionized
      and natural water.
AB  - The photodegradation of organic phosphorus is one of the most important processes
      of the phosphorus cycle by which phosphate is regenerated in the water
      environment. In this study, the influence of direct photolysis or indirect
      photolysis of organic phosphorus using natural photosensitizers on the released
      phosphate was examined in deionized and natural water under ultraviolet (UV)
      irradiation using diazinon as the organic phosphorus model. Phosphate was
      released when diazinon was exposed to UV light, and the solution pH also
      exhibited distinct influences on the phosphate that was released from diazinon
      photodegradation. When the natural photosensitizers were added, the amount of
      phosphate released increased significantly because of the diazinon indirect
      photodegradation by reactive species, such as the hydroxyl radical generated by
      NO3- and Fe3+. However, humic acid and HCO3- inhibited the phosphate released by
      a radical scavenging effect. When natural water was spiked with diazinon, the
      phosphate that was released in natural water was higher than that of the control
      or deionized water, and the phosphate that was released was inhibited when
      isopropanol was added to the reaction. In addition, the formation of hydroxyl
      radicals (OH) in the natural water systems was identified from the
      photoluminescence spectra using coumarin as the trapping molecule, and the steady
      state concentration of OH in natural water was 3.07 +/- 0.57 * 10-16 M under UV
      irradiation. All of these results indicated that direct and indirect photolysis
      degradation of organic phosphorus significantly impacts the release of phosphate
      in surface waters.

PMID- 27878157
TI  - Ruthenium water oxidation catalysts containing the non-planar tetradentate
      ligand, biisoquinoline dicarboxylic acid (biqaH2).
AB  - Two ruthenium complexes containing the tetradentate ligand [1,1'-biisoquinoline]
      3,3'-dicarboxylic acid, and 4-picoline or 6-bromoisoquinoline as axial ligands
      have been prepared. The complexes have been fully characterised and initial
      studies on their potential to function as molecular water oxidation catalysts
      have been performed. Both complexes catalyse the oxidation of water in acidic
      media with CeIV as a stoichiometric chemical oxidant, although turnover numbers
      and turnover frequencies are modest when compared with the closely related Ru-bda
      and Ru-pda analogues. Barriers for the water nucleophilic attack and
      intermolecular coupling pathways were obtained from density functional theory
      calculations and the crucial influence of the ligand framework in determining the
      most favourable reaction pathway was elucidated from a combined analysis of the
      theoretical and experimental results.

PMID- 27878159
TI  - The synthesis and structure of a dianionic species with a bond between
      pentacoordinated tin atoms: bonding properties of the tin-tin bond.
AB  - The first dianionic compound bearing a bond between two pentacoordinated tin
      atoms, a distannate, was synthesized in a stable form by using two sets of an
      electron-withdrawing C,O-bidentate ligand on each tin atom. The structure of the
      distannate was determined by NMR spectroscopy and X-ray crystallographic
      analysis. The Sn-Sn bond of the distannate was shown to be a single bond
      featuring high s-character. The 1J(Sn-Sn) coupling constant was larger than that
      of Sn(sp3)-Sn(sp3) bonds found in most hexaorganodistannanes. This bond feature
      was also supported by computational studies. The Sn-Sn bond was cleaved by
      treatment with hydrochloric acid, which shows a different reactivity to the
      homonuclear bonds of pentacoordinated disilicates and digermanates.

PMID- 27878160
TI  - Chemo-enzymatic modification of eukaryotic mRNA.
AB  - Messenger RNA may not be very abundant in the cell but its central role in gene
      expression is indisputable. In addition to being the template for translation it
      can be subject for a variety of regulatory mechanisms affecting gene expression,
      ranging from simple structural changes to modifications and active transport. To
      elucidate and potentially control the underlying changes in vitro and in cells,
      site-specific modification and labeling strategies are required. In this
      perspective, we introduce chemo-enzymatic concepts for posttranscriptional
      modification focusing on eukaryotic mRNAs. We describe how eukaryotic mRNA can be
      enzymatically modified via its 5' cap. Directions towards chemo-enzymatic mRNA
      labeling and visualization inside cells are given, taking into account current
      developments in fluorophore design. Recent achievements and future perspectives
      will be highlighted in the framework of an honest discussion of existing
      challenges.

PMID- 27878161
TI  - One-pot conversion reactions of glycosyl boranophosphates into glycosyl phosphate
      derivatives via acyl phosphite intermediates.
AB  - A one-pot synthesis of glycosyl phosphates and their P-modified analogs from
      glycosyl boranophosphates under mild basic conditions has been conducted. 31P NMR
      monitoring of the reaction mixture revealed that the key intermediates of these
      reactions were acyl phosphites, which could not be formed from the corresponding
      H-phosphonate diesters.

PMID- 27878163
TI  - Radical-promoted site-specific cross dehydrogenative coupling of heterocycles
      with nitriles.
AB  - A first free-radical triggered site-specific cross dehydrogenative coupling
      reaction of heterocycles with simple nitriles is developed. It allows efficient
      and facile access to various C-2 cyanoalkylated furans, thiophenes, indoles, and
      pyrroles. The extremely high selectivities in this case indicate that
      functionalization of an inert C-H bond could be well-controlled by radical
      initiation.

PMID- 27878162
TI  - Asymmetric chemoenzymatic synthesis of 1,3-diols and 2,4-disubstituted
      aryloxetanes by using whole cell biocatalysts.
AB  - Regio- and stereo-selective reduction of substituted 1,3-aryldiketones,
      investigated in the presence of different whole cell microorganisms, was found to
      afford beta-hydroxyketones or 1,3-diols in very good yields (up to 95%) and
      enantiomeric excesses (up to 96%). The enantiomerically enriched aldols, obtained
      with the opposite stereo-preference by baker's yeast and Lactobacillus reuteri
      DSM 20016 bioreduction, could then be diastereoselectively transformed into
      optically active syn- or anti-1,3-diols by a careful choice of the chemical
      reducing agent (diastereomeric ratio up to 98 : 2). The latter, in turn, were
      stereospecifically cyclized into the corresponding oxetanes in 43-98% yields and
      in up to 94% ee, thereby giving a diverse selection of stereo-defined 2,4
      disubstituted aryloxetanes.

PMID- 27878164
TI  - Outflow and clogging of shape-anisotropic grains in hoppers with small apertures.
AB  - Outflow of granular material through a small orifice is a fundamental process in
      many industrial fields, for example in silo discharge, and in everyday's life.
      Most experimental studies of the dynamics have been performed so far with
      monodisperse disks in two-dimensional (2D) hoppers or spherical grains in 3D. We
      investigate this process for shape-anisotropic grains in 3D hoppers and discuss
      the role of size and shape parameters on avalanche statistics, clogging states,
      and mean flow velocities. It is shown that an increasing aspect ratio of the
      grains leads to lower flow rates and higher clogging probabilities compared to
      spherical grains. On the other hand, the number of grains forming the clog is
      larger for elongated grains of comparable volumes, and the long axis of these
      blocking grains is preferentially aligned towards the center of the orifice. We
      find a qualitative transition in the hopper discharge behavior for aspect ratios
      larger than ~6. At still higher aspect ratios >8-12, the outflowing material
      leaves long vertical holes in the hopper that penetrate the complete granular
      bed. This changes the discharge characteristics qualitatively.

PMID- 27878165
TI  - Chemoselective hydrogenation of arenes by PVP supported Rh nanoparticles.
AB  - Polyvinylpyrrolidone-stabilized Rh nanoparticles (RhNPs/PVP) of ca. 2.2 nm in
      size were prepared by the hydrogenation of the organometallic complex [Rh(eta3
      C3H5)3] in the presence of PVP and evaluated as a catalyst in the hydrogenation
      of a series of arene substrates as well as levulinic acid and methyl levulinate.
      The catalyst showed excellent activity and selectivity towards aromatic ring
      hydrogenation compared to other reported transition metal-based catalysts under
      mild reaction conditions (room temperature and 1 bar H2). Furthermore, it was
      shown to be a highly promising catalyst for the hydrogenation of levulinic acid
      and methyl levulinate in water leading to quantitative formation of the fuel
      additive gamma-valerolactone under moderate reaction conditions compared to
      previously reported catalytic systems.

PMID- 27878166
TI  - Mechanism of excited state deactivation of indan-1-ylidene and fluoren-9-ylidene
      malononitriles.
AB  - Herein, we report complementary computational and experimental evidence
      supporting the existence, for indan-1-ylidene malononitrile and fluoren-9-ylidene
      malononitrile, of a non-radiative decay channel involving double bond
      isomerisation motion. The results of UV-Vis transient absorption spectroscopy
      highlight that the decay takes place within hundreds of picoseconds. In order to
      understand the related molecular mechanism, photochemical reaction paths were
      computed by employing multiconfigurational quantum chemistry. The results
      indicate that the excited state deactivation occurs via concerted double bond
      twisting of the dicyanovinyl (DCV) unit coupled with a pyramidalisation of its
      substituted carbon. It is also shown that the observed differences in the excited
      state lifetimes when passing from indan-1-ylidene malononitrile to fluoren-9
      ylidene are associated with the change in the topography of the conical
      intersection driving the decay from intermediate to sloped, respectively.

PMID- 27878167
TI  - Gradient doping - a case study with Ti-Fe2O3 towards an improved
      photoelectrochemical response.
AB  - The present study investigates the effect of gradient doping on modifying the
      photoelectrochemical response of Ti-doped Fe2O3 photoanodes for their use in
      sunlight based water splitting for hydrogen evolution. The deposition of a thin
      film over the ITO (tin doped indium oxide) substrate was carried out using a
      spray pyrolysis method. The concentration of dopant was varied from 0.5-8.0 at%
      and two sets of samples were also prepared with low to high (0.5-8%) and high to
      low (8-0.5%) dopant concentrations in the direction towards the substrate. The
      prepared thin films were characterized using X-ray Diffractometry (XRD), Scanning
      Electron Microscopy (SEM), Energy Dispersive X-ray (EDX) Spectroscopy, Secondary
      Ion Mass Spectroscopy (SIMS), X-ray Photoelectron Spectroscopy (XPS) and UV
      visible Spectroscopy. The photoelectrochemical studies revealed that the
      deposition of dopant layers with a low to high concentration towards the
      substrate exhibited a highly improved photoresponse (200 times) in comparison to
      the pristine sample and a two fold enhancement in comparison to 2% Ti-doped
      Fe2O3. The improvement in the photoresponse has been attributed to the values of
      a high flat band potential, low resistance, high open circuit voltage, carrier
      separation efficiency, applied bias photon-to-current conversion efficiency
      (ABPE), and incident photon-to-current conversion efficiency (IPCE). A reduced
      charge transfer resistance has been demonstrated with Nyquist plots.

PMID- 27878168
TI  - Comparison of hydration behavior and conformational preferences of the Trp-cage
      mini-protein in different rigid-body water models.
AB  - The secondary structure conformational properties and hydration shell metrics of
      the Trp-cage mini-protein are examined in the folded and unfolded ensembles in
      mTIP3P, TIP4P, and TIP4P-Ew water models with the CHARMM22 force-field using
      molecular dynamics simulations at 250 K. Upon changing the water model, the
      conformational order metrics of the peptide show significant differences in the
      unfolded rather than in the folded ensemble. The unfolding temperatures for Trp
      cage are observed to be around 460, 470, and 430 K in mTIP3P, TIP4P, and TIP4P
      Ew, respectively. Upon comparing the results with a previous study on a 16
      residue beta-hairpin fragment of the 2GB1 protein, the same set of conformational
      order metrics are found to be insufficient in describing the free energy
      landscape of peptides having a distinct native secondary structure. However, the
      hydration shell properties of the peptide have been found to be independent of
      the sequence of the peptide and it changes in conformation upon unfolding. Our
      calculations reveal that for a particular water model, the secondary structure
      preferences in the unfolded ensembles of the two peptides are qualitatively
      different. The unfolded structures of Trp-cage prefer extended and compact
      structures in TIP4P-Ew and mTIP3P water, respectively, whereas the beta-hairpin
      peptide prefers extended unfolded structures in mTIP3P. The conformational
      preferences of the unfolded peptide in a given water model have been found to
      depend on the peptide sequence, where the binding energies of the water molecules
      around the polar residues in the unfolded conformations show sensitivity to the
      multipole moments of the water models. The significance of an accurate
      description of peptide-solvent interactions in the parametrization of
      biomolecular force-fields, to obtain an accurate description of conformational
      preferences, in particular in the unfolded ensembles of proteins, is highlighted.

PMID- 27878169
TI  - In situ characterisation of nanostructured multiphase thermoelectric materials at
      elevated temperatures.
AB  - Multiphase thermoelectric materials have recently attracted considerable
      attention due to the high thermoelectric efficiencies which can be achieved in
      these compounds compared to their single-phase counterparts. However, there is
      very little known on the structural evolution of these phases as a function of
      temperature. In this work we performed an in situ high temperature structural
      characterisation of recently reported high efficiency p-type multiphase
      (PbTe)0.65(PbS)0.25(PbSe)0.1 compounds by hot stage transmission electron
      microscopy and high-resolution neutron powder diffraction. We observed the
      microstructural evolution of precipitates and determined the lattice parameters
      of phases as a function of temperature for materials, which have been heavily and
      lightly doped with sodium. The role of the sodium is to optimize the
      concentration of charge carriers. It has been shown to distribute heterogeneously
      between the phases in multiphase compounds. The dissolution of secondary phases
      is found to occur at elevated temperatures. Although sodium concentration
      produces no significant differences between the lattice constants of the phases
      and the dissolution sequence of precipitates, it affects quite significantly the
      kinetics of precipitation. The heavily doped samples reach structural
      thermodynamic equilibrium more quickly than the lightly doped compound. These
      results are a step forward in designing high performance multiphase
      thermoelectric materials.

PMID- 27878171
TI  - Fine regulation of cellulose dissolution and regeneration by low pressure CO2 in
      DMSO/organic base: dissolution behavior and mechanism.
AB  - In this study, the fine regulation of the dissolution and regeneration of
      microcrystalline cellulose (MCC) using very low pressure (0-0.2 MPa) CO2 in a
      mixed solvent of dimethyl sulfoxide (DMSO) and 1,8-diazabicyclo-[5.4.0]-undec-7
      ene (DBU) at a very low temperature (30  degrees C) was achieved. The solubility
      of MCC in DMSO/DBU (weight ratio of DMSO WDMSO = 0.90) could reach 9.0% at 30 
      degrees C and under CO2 pressure of 0.2 MPa. A similar phenomenon was observed in
      the mixed solvent DMSO/1,1,3,3-tetramethylguanidine (TMG). Moreover, ATR-FTIR,
      NMR, UV-Vis, TGA, XRD and DFT computational analyses were used to investigate the
      dissolution mechanism. It was concluded that in the mixed solvent (DMSO and
      organic base), DMSO helped to dissociate ion-pairs into free ions by balancing
      the concentration of free ions and the number of hydrogen bonds at WDMSO = 0.90.
      Interactions between CO2 and the solvent mixture were explored, and the results
      indicate that the optimum CO2 pressure not only promotes the formation of ionic
      bonds but also accelerates the formation of covalent bonds. In this way, these
      interactions prevent the MCC molecules from aggregating and facilitate the
      dissolving of MCC. This study gives a thorough insight into the dissolution
      mechanism and specificity of MCC in the CO2-DMSO/organic base solvent system,
      which could be helpful for the utilization and transformation of cellulose.

PMID- 27878170
TI  - Absolute cross-sections for DNA strand breaks and crosslinks induced by low
      energy electrons.
AB  - Absolute cross sections (CSs) for the interaction of low energy electrons with
      condensed macromolecules are essential parameters to accurately model ionizing
      radiation induced reactions. To determine CSs for various conformational DNA
      damage induced by 2-20 eV electrons, we investigated the influence of the
      attenuation length (AL) and penetration factor (f) using a mathematical model.
      Solid films of supercoiled plasmid DNA with thicknesses of 10, 15 and 20 nm were
      irradiated with 4.6, 5.6, 9.6 and 14.6 eV electrons. DNA conformational changes
      were quantified by gel electrophoresis, and the respective yields were
      extrapolated from exposure-response curves. The absolute CS, AL and f values were
      generated by applying the model developed by Rezaee et al. The values of AL were
      found to lie between 11 and 16 nm with the maximum at 14.6 eV. The absolute CSs
      for the loss of the supercoiled (LS) configuration and production of crosslinks
      (CL), single strand breaks (SSB) and double strand breaks (DSB) induced by 4.6,
      5.6, 9.6 and 14.6 eV electrons are obtained. The CSs for SSB are smaller, but
      similar to those for LS, indicating that SSB are the main conformational damage.
      The CSs for DSB and CL are about one order of magnitude smaller than those of LS
      and SSB. The value of f is found to be independent of electron energy, which
      allows extending the absolute CSs for these types of damage within the range 2-20
      eV, from previous measurements of effective CSs. When comparison is possible, the
      absolute CSs are found to be in good agreement with those obtained from previous
      similar studies with double-stranded DNA. The high values of the absolute CSs of
      4.6 and 9.6 eV provide quantitative evidence for the high efficiency of low
      energy electrons to induce DNA damage via the formation of transient anions.

PMID- 27878172
TI  - Understanding the role of hydrogen bonding in Bronsted acidic ionic liquid
      catalyzed transesterification: a combined theoretical and experimental
      investigation.
AB  - Bronsted acidic ionic liquids (BAILs) can play a dual role, as a solvent and as a
      catalyst, in many reactions. However, molecular details of the catalytic
      mechanism are poorly understood. We present here a density functional theory
      (DFT) study for the catalytic mechanism of the transesterification of methyl
      ester (ME) with trimethylolpropane (TMP), in the presence of three representative
      BAILs, namely, N-methylimidazole-IL, pyridinium-IL, and triethylamine-IL. The
      deprotonation of the BAIL cation and the transesterification step are
      investigated. Key inter- and intra-molecular hydrogen bonds (HBs) that govern the
      catalytic performance of BAILs were identified and analyzed using natural bond
      orbital (NBO) and atoms in molecule (AIM) methods. For the deprotonation of
      BAILs, it was found that the intermolecular O-HO HB between the hydroxyl group of
      TMP and the oxygen of the sulfonic group of BAIL was indispensable for proton
      transfer. DFT computed free energy barriers for the transesterification step are
      in excellent agreement with the experimental results only after taking into
      account the BAIL cation-anion interaction in terms of HBs in which the O-HO
      between the hydroxyl group of the anion and the oxygen of the sulfonic group of
      the cation was the strongest HB, suggesting the role of the anion in governing
      the catalytic activity of BAILs. The existence of the HBs suggested by DFT
      calculations was further validated using in situ FTIR experiments/ATR-FTIR.

PMID- 27878173
TI  - Silver-doped molybdenum carbide catalyst with high activity for electrochemical
      water splitting.
AB  - A hybrid catalyst composed of silver (Ag) doped wire-like molybdenum carbide
      (MoxCy) with pure beta-phase and carbon nanotubes (CNTs) was coated well on a
      carbon rod electrode for the hydrogen evolution reaction (HER). The effects of Ag
      loading amount and carbonization temperature on the crystal form of MoxCy were
      investigated in detail. It is found that the MoxCy crystal form can be tuned by
      adjusting the preparation conditions, and nanostructured wire-like Mo2C with pure
      beta-phase was obtained at a temperature over 750  degrees C. Ag/MoxCy composite
      nanomaterials were investigated by X-ray diffraction, UV/vis spectroscopy, X-ray
      photoelectron spectroscopy, scanning electron microscopy, transmission electron
      microscopy, energy-dispersive spectroscopy and Brunauer-Emmett-Teller surface
      area analysis. The hybrid catalyst was further deposited on the carbon nanotube
      (CNT) modified carbon rod substrate. Due to the high surface area and 3D porous
      network-like microstructure, the Ag/Mo2C/CNTs hybrid electrode showed enhanced
      catalytic performance when comparing with the corresponding pure one.
      Particularly, for the Ag-doped Mo2C/CNTs hybrid electrode with an optimum 1 Ag :
      5 Mo molar ratio of the precursors, a current density of 10 mA cm-2 was obtained
      by applying an overpotential of 142 mV in 0.5 mol L-1 H2SO4 solution. It is
      expected that such a hybrid electrode can be widely applied for effective
      electrolysis of water to produce hydrogen.

PMID- 27878174
TI  - Dynamic DNA-controlled "stop-and-go" assembly of well-defined protein domains on
      RNA-scaffolded TMV-like nanotubes.
AB  - A DNA-based approach allows external control over the self-assembly process of
      tobacco mosaic virus (TMV)-like ribonucleoprotein nanotubes: their growth from
      viral coat protein (CP) subunits on five distinct RNA scaffolds containing the
      TMV origin of assembly (OAs) could be temporarily blocked by a stopper DNA
      oligomer hybridized downstream (3') of the OAs. At two upstream (5') sites
      tested, simple hybridization was not sufficient for stable stalling, which
      correlates with previous findings on a non-symmetric assembly of TMV. The growth
      of DNA-arrested particles could be restarted efficiently by displacement of the
      stopper via its toehold by using a release DNA oligomer, even after storage for
      twelve days. This novel strategy for growing proteinaceous tubes under tight
      kinetic and spatial control combines RNA guidance and its site-specific but
      reversible interruption by DNA blocking elements. As three of the RNA scaffolds
      contained long heterologous non-TMV sequence portions that included the stopping
      sites, this method is applicable to all RNAs amenable to TMV CP encapsidation,
      albeit with variable efficiency most likely depending on the scaffolds' secondary
      structures. The use of two distinct, selectively addressable CP variants during
      the serial assembly stages finally enabled an externally configured fabrication
      of nanotubes with highly defined subdomains. The "stop-and-go" strategy thus
      might pave the way towards production routines of TMV-like particles with
      variable aspect ratios from a single RNA scaffold, and of nanotubes with two or
      even more adjacent protein domains of tightly pre-defined lengths.

PMID- 27878175
TI  - Synergistic effects of mining and urban effluents on the level and distribution
      of methylmercury in a shallow aquatic ecosystem of the Bolivian Altiplano.
AB  - Lake Uru Uru (3686 m a.s.l.) located in the Bolivian Altiplano region receives
      both mining effluents and urban wastewater discharges originating from the
      surrounding local cities which are under rapid development. We followed the
      spatiotemporal distribution of different mercury (Hg) compounds and other
      metal(oid)s (e.g., Fe, Mn, Sb, Ti and W) in both water and sediments during the
      wet and dry seasons along a north-south transect of this shallow lake system.
      Along the transect, the highest Hg and metal(oid) concentrations in both water
      and sediments were found downstream of the confluences with mining effluents.
      Although a dilution effect was found for major elements during the wet season,
      mean Hg and metal(oid) concentrations did not significantly differ from the dry
      season due to the increase in acid mine drainage (AMD) inputs into the lake from
      upstream mining areas. In particular, high filtered (<0.45 MUm) mono
      methylmercury (MMHg) concentrations (0.69 +/- 0.47 ng L-1) were measured in
      surface water representing 49 +/- 11% of the total filtered Hg concentrations
      (THgF) for both seasons. Enhanced MMHg lability in relation with the water
      alkalinity, coupled with abundant organic ligands and colloids (especially for
      downstream mining effluents), are likely factors favoring Hg methylation and MMHg
      preservation while inhibiting MMHg photodegradation. Lake sediments were
      identified as the major source of MMHg for the shallow water column. During the
      dry season, diffusive fluxes were estimated to be 227 ng m-2 d-1 for MMHg. This
      contribution was found to be negligible during the wet season due to a probable
      shift of the redox front downwards in the sediments. During the wet season, the
      results obtained suggest that various sources such as mining effluents and
      benthic or macrophytic biofilms significantly contribute to MMHg inputs in the
      water column. This work demonstrates the seasonally dependent synergistic effect
      of AMD and urban effluents on the shallow, productive and evaporative high
      altitude lake ecosystems which promotes the formation of natural organometallic
      toxins such as MMHg in the water column.

PMID- 27878176
TI  - Na2CoSiO4 as a cathode material for sodium-ion batteries: structure,
      electrochemistry and diffusion pathways.
AB  - The importance of developing new low-cost and safe cathodes for large-scale
      sodium batteries has led to recent interest in silicate compounds. A novel cobalt
      orthosilicate, Na2CoSiO4, shows promise as a high voltage (3.3 V vs. Na/Na+)
      cathode material for sodium-ion batteries. Here, the synthesis and room
      temperature electrochemical performance of Na2CoSiO4 have been investigated with
      the compound found to yield a reversible capacity greater than 100 mA h g-1 at a
      rate of 5 mA g-1. Insights into the crystal structures of Na2CoSiO4 were obtained
      through refinement of structural models for its two polymorphs, Pn and Pbca.
      Atomistic modelling results indicate that intrinsic defect levels are not
      significant and that Na+ diffusion follows 3D pathways with low activation
      barriers, which suggest favourable electrode kinetics. The new findings presented
      here provide a platform on which future optimisation of Na2CoSiO4 as a cathode
      for Na-ion batteries can be based.

PMID- 27878177
TI  - Gate-controlled conductance enhancement from quantum Hall channels along graphene
      p-n junctions.
AB  - The formation of quantum Hall channels inside the bulk of graphene is studied
      using various contact and gate geometries. p-n junctions are created along the
      longitudinal direction of samples, and enhanced conductance is observed in the
      case of bipolar doping due to the new conducting channels formed in the bulk,
      whose position, propagating direction and, in one geometry, coupling to
      electrodes are determined by the gate-controlled filling factor across the
      device. This effect could be exploited to probe the behavior and interaction of
      quantum Hall channels protected against uncontrolled scattering at the edges.

PMID- 27878178
TI  - Enhanced hydrogen storage properties of MgH2 co-catalyzed with K2NiF6 and CNTs.
AB  - The composite of MgH2/K2NiF6/carbon nanotubes (CNTs) is prepared by ball milling,
      and its hydrogenation properties are studied for the first time. MgH2 co
      catalyzed with K2NiF6 and CNTs exhibited an improvement in the onset
      dehydrogenation temperature and isothermal de/rehydrogenation kinetics compared
      with the MgH2-K2NiF6 composite. The onset dehydrogenation temperature of MgH2
      doped with 10 wt% K2NiF6 and 5 wt% CNTs is 245  degrees C, which demonstrated a
      reduction of 25  degrees C compared with the MgH2 + 10 wt% K2NiF6 composite. In
      terms of rehydrogenation kinetics, MgH2 doped with 10 wt% K2NiF6 and 5 wt% CNTs
      samples absorbed 3.4 wt% of hydrogen in 1 min at 320  degrees C, whereas the MgH2
      + 10 wt% K2NiF6 sample absorbed 2.6 wt% of hydrogen under the same conditions.
      For dehydrogenation kinetics at 320  degrees C, the MgH2 + 10 wt% K2NiF6 + 5 wt%
      CNTs sample released 3.3 wt% hydrogen after 5 min of dehydrogenation. By
      contrast, MgH2 doped with 10 wt% K2NiF6 released 3.0 wt% hydrogen in the same
      time period. The apparent activation energy, Ea, for the dehydrogenation of MgH2
      doped with 10 wt% K2NiF6 reduced from 100.0 kJ mol-1 to 70.0 kJ mol-1 after MgH2
      was co-doped with 10 wt% K2NiF6 and 5 wt% CNTs. Based on the experimental
      results, the hydrogen storage properties of the MgH2/K2NiF6/CNTs composite is
      enhanced because of the catalytic effects of the active species of KF, KH and
      Mg2Ni that are formed in situ during dehydrogenation, as well as the unique
      structure of CNTs.

PMID- 27878179
TI  - When biomolecules meet graphene: from molecular level interactions to material
      design and applications.
AB  - Graphene-based materials have attracted increasing attention due to their
      atomically-thick two-dimensional structures, high conductivity, excellent
      mechanical properties, and large specific surface areas. The combination of
      biomolecules with graphene-based materials offers a promising method to fabricate
      novel graphene-biomolecule hybrid nanomaterials with unique functions in biology,
      medicine, nanotechnology, and materials science. In this review, we focus on a
      summarization of the recent studies in functionalizing graphene-based materials
      using different biomolecules, such as DNA, peptides, proteins, enzymes,
      carbohydrates, and viruses. The different interactions between graphene and
      biomolecules at the molecular level are demonstrated and discussed in detail. In
      addition, the potential applications of the created graphene-biomolecule
      nanohybrids in drug delivery, cancer treatment, tissue engineering, biosensors,
      bioimaging, energy materials, and other nanotechnological applications are
      presented. This review will be helpful to know the modification of graphene with
      biomolecules, understand the interactions between graphene and biomolecules at
      the molecular level, and design functional graphene-based nanomaterials with
      unique properties for various applications.

PMID- 27878180
TI  - From evaporation-induced self-assembly to shear-induced alignment.
AB  - The functionality of compact nanostructured thin films depends critically on the
      degree of order and hence on the underlying ordering mechanisms during film
      formation. For dip coating of rigid nanorods the counteracting mechanisms,
      evaporation-induced self-assembly (EISA) and shear-induced alignment (SIA) have
      recently been identified as competing ordering mechanisms. Here, we show how to
      achieve highly ordered and homogeneous thin films by controlling EISA and SIA in
      dip coating. Therefore we identify the influences of the process parameters
      including temperature, initial volume fraction and nanorod aspect ratio on
      evaporation-induced convective flow and externally applied shear forces and
      evaluate the resulting films. The impact of evaporation and shear can be
      distinguished by analysing film thickness, surface order and bulk order by
      careful in situ SAXS, Raman and SEM-based image analysis. For the first time we
      derive processing guidelines for the controlled application of EISA and SIA
      towards highly ordered thin nematic films.

PMID- 27878181
TI  - Self-assembled monolayer structures of hexadecylamine on Cu surfaces: density
      functional theory.
AB  - We used dispersion-corrected density-functional theory to probe possible
      structures for adsorbed layers of hexadecylamine (HDA) on Cu(100) and Cu(111).
      HDA forms self-assembled layers on these surfaces, analogous to alkanethiols on
      various metal surfaces, and it binds by donating electrons in the amine group to
      the Cu surface atoms, consistent with experiment. van der Waals interactions
      between the alkyl tails of HDA molecules are stronger than the interaction
      between the amine group and the Cu surfaces. Strong HDA-tail interactions lead to
      coverage-dependent tilting of the HDA layers, such that the tilt angle is larger
      for lower coverages. At full monolayer coverage, the energetically preferred
      binding configuration for HDA on Cu(100) is a (5 * 3) pattern - although we
      cannot rule out incommensurate structures - while the pattern is preferred on
      Cu(111). A major motivation for this study is to understand the experimentally
      observed capability of HDA as a capping agent for producing {100}-faceted Cu
      nanocrystals. Consistent with experiment, we find that HDA binds more strongly to
      Cu(100) than to Cu(111). This strong binding stems from the capability of HDA to
      form more densely packed layers on Cu(100), which leads to stronger HDA-tail
      interactions, as well as the stronger binding of the amine group to Cu(100). We
      estimate the surface energies of HDA-covered Cu(100) and Cu(111) surfaces and
      find that these surfaces are nearly isoenergetic. By drawing analogies to
      previous theoretical work, it seems likely that HDA-covered Cu nanocrystals could
      have kinetic shapes that primarily express {100} facets, as is seen
      experimentally.

PMID- 27878182
TI  - Characterisation, degradation and regeneration of luminescent Ag29 clusters in
      solution.
AB  - Luminescent Ag clusters are prepared with lipoic acid (LA) as the ligand. Using a
      combination of mass spectrometry, optical spectroscopy and analytical
      ultracentrifugation, the clusters are found to be highly monodisperse with mass
      5.6 kDa. We assign the chemical composition [Ag29(LA)12]3- to the clusters, where
      LA likely binds in a bidentate fashion. The Ag29 clusters show slow degradation,
      retaining their deep red emission for at least 18 months if stored in the dark.
      Purification or exposure to light results in faster degradation. No other cluster
      species are observed during the degradation process. Once degraded, the clusters
      could easily be regenerated using NaBH4, which is not usually observed for
      thiolate-capped Ag clusters.

PMID- 27878186
TI  - Towards an understanding of amyloid-beta oligomers: characterization, toxicity
      mechanisms, and inhibitors.
AB  - Alzheimer's disease (AD) is characterized by an imbalance between production and
      clearance of amyloid-beta (Abeta) species. Abeta peptides can transform
      structurally from monomers into beta-stranded fibrils via multiple oligomeric
      states. Among the various Abeta species, structured oligomers are proposed to be
      more toxic than fibrils; however, the identification of Abeta oligomers has been
      challenging due to their heterogeneous and metastable nature. Multiple techniques
      have recently helped us gain a better understanding of oligomers' assembly
      details and structural properties. Moreover, some progress on elucidating the
      mechanisms of oligomer-triggered toxicity has been made. Based on the collection
      of current findings, there is growing consensus that control of toxic Abeta
      oligomers could be a valid approach to regulate Abeta-associated toxicity, which
      could advance development of new diagnostics and therapeutics for amyloid-related
      diseases. In this review, we summarize the recent understanding of Abeta
      oligomers' assembly, structural properties, and toxicity, along with inhibitors
      against Abeta aggregation, including oligomerization.

PMID- 27878188
TI  - Organic-inorganic perovskite plasmonic nanowire lasers with a low threshold and a
      good thermal stability.
AB  - Plasmonic nanolasers have ushered in a paradigm of deep sub-wavelength coherent
      optical sources with ultrafast dynamics that exploit the strong confinement
      capabilities of metals. Although these devices are usually associated with higher
      thresholds due to absorption in metals, the high gain inorganic II-VI and III-V
      semiconductor materials have allowed the realization of plasmonic nanolasers
      operating under ambient conditions. In this work, we introduce single-crystalline
      lead halide perovskite (CH3NH3PbI3) nanowires as an organic-inorganic
      semiconducting gain material to the plasmonic laser community. We demonstrate
      plasmonic laser action using a hybrid geometry whereby the perovskite nanowires
      are placed on a silver substrate with an insulating spacer layer. We report
      relatively low threshold operation under ambient conditions (13.5 MUJ cm-2), and
      the devices work well even at temperatures up to 43.6  degrees C. The
      demonstration highlights the high optical gain achievable in perovskite materials
      and thus provides a solution to high gain materials for plasmonic devices.

PMID- 27878192
TI  - Ion transport in graphene nanofluidic channels.
AB  - Carbon nanofluidic structures made of carbon nanotubes or graphene/graphene oxide
      have shown great promise in energy and environment applications due to the newly
      discovered fast and selective mass transport. However, they have yet to be
      utilized in nanofluidic devices for lab-on-a-chip applications because of great
      challenges in their fabrication and integration. Herein we report the fabrication
      of two-dimensional planar graphene nanochannel devices and the study of ion
      transport inside a graphene nanochannel array. A MEMS fabrication process that
      includes controlled nanochannel etching, graphene wet transfer, and vacuum anodic
      bonding is developed to fabricate graphene nanochannels where graphene
      conformally coats the channel surfaces. We observe higher ionic conductance
      inside the graphene nanochannels compared with silica nanochannels with the same
      geometries at low electrolyte concentrations (10-6 M-10-2 M). Enhanced
      electroosmotic flow due to the boundary slip at graphene surfaces is attributed
      to the measured higher conductance in the graphene nanochannels. Our results also
      suggest that the surface charge on the graphene surface, originating from the
      dissociation of oxygen-containing functional groups, is crucial to the enhanced
      electroosmotic flow inside the nanochannels.

PMID- 27878193
TI  - Efficient near-infrared light-emitting diodes based on organometallic halide
      perovskite-poly(2-ethyl-2-oxazoline) nanocomposite thin films.
AB  - Organometallic halide perovskites have recently drawn considerable attention for
      applications in light emission diodes (LEDs). However, the small exciton binding
      energy of the CH3NH3PbI3 perovskite has the concerns of large exciton
      dissociation and low radiative recombination on its use in near-infrared LEDs
      (NIR-LEDs). Herein, we propose and demonstrate that the introduction of poly(2
      ethyl-2-oxazoline) (PEtOz) into the perovskite can simultaneously improve the
      recombination rate and radiative decay rate for improving perovskite LED
      performances. Additionally, our approach results in smooth perovskite films with
      increased thickness, reduced roughness, and pin-hole free, which facilitates
      other film deposition on top for practical device fabrication, and reduces
      current leakage. After optimizing the perovskite-PEtOz nanocomposite emission
      layer in NIR-LEDs (emission peak at 760 nm), a high radiance of 12.3 W sr-1 m-2
      and 70-fold enhancement of the external quantum efficiency (EQE) compared to that
      of the pristine perovskite case are achieved. The maximum EQE reaches 0.76%,
      which is the highest EQE reported so far for the CH3NH3PbI3 based NIR-LEDs. The
      simplicity of our fabrication approach combined with the outstanding device
      performances further highlights the enormous potential of perovskite-based LEDs.

PMID- 27878189
TI  - Mapping cellular Fe-S cluster uptake and exchange reactions - divergent pathways
      for iron-sulfur cluster delivery to human ferredoxins.
AB  - Ferredoxins are protein mediators of biological electron-transfer reactions and
      typically contain either [2Fe-2S] or [4Fe-4S] clusters. Two ferredoxin homologues
      have been identified in the human genome, Fdx1 and Fdx2, that share 43% identity
      and 69% similarity in protein sequence and both bind [2Fe-2S] clusters. Despite
      the high similarity, the two ferredoxins play very specific roles in distinct
      physiological pathways and cannot replace each other in function. Both eukaryotic
      and prokaryotic ferredoxins and homologues have been reported to receive their Fe
      S cluster from scaffold/delivery proteins such as IscU, Isa, glutaredoxins, and
      Nfu. However, the preferred and physiologically relevant pathway for receiving
      the [2Fe-2S] cluster by ferredoxins is subject to speculation and is not clearly
      identified. In this work, we report on in vitro UV-visible (UV-vis) circular
      dichroism studies of [2Fe-2S] cluster transfer to the ferredoxins from a variety
      of partners. The results reveal rapid and quantitative transfer to both
      ferredoxins from several donor proteins (IscU, Isa1, Grx2, and Grx3). Transfer
      from Isa1 to Fdx2 was also observed to be faster than that of IscU to Fdx2,
      suggesting that Fdx2 could receive its cluster from Isa1 instead of IscU. Several
      other transfer combinations were also investigated and the results suggest a
      complex, but kinetically detailed map for cellular cluster trafficking. This is
      the first step toward building a network map for all of the possible iron-sulfur
      cluster transfer pathways in the mitochondria and cytosol, providing insights on
      the most likely cellular pathways and possible redundancies in these pathways.

PMID- 27878194
TI  - Fully gravure printed complementary carbon nanotube TFTs for a clock signal
      generator using an epoxy-imine based cross-linker as an n-dopant and encapsulant.
AB  - Printed p-type single walled carbon nanotube (SWCNT) based circuits exhibit high
      power dissipation owing to their thick printed dielectric layers (>2 MUm) and
      long channels (>100 MUm). In order to reduce the static power dissipation of
      printed SWCNT-base circuits while maintaining the same printing conditions and
      channel lengths, complementary metal-oxide-semiconductor (CMOS) based circuits
      are more ideal. These circuits, however, have not been successfully implemented
      in a scalable printing platform due to unstable threshold voltages of n-doped
      SWCNT based thin film transistors (TFTs). In this work, a thermally curable epoxy
      imine-based n-doping ink is presented for achieving uniform doping and sealing of
      SWCNT layers by gravure printing. After printing the n-doping ink, the ink is
      cured to initiate a cross-linking reaction to seal the n-doped SWCNT-TFTs so that
      the threshold voltage of the n-doped SWCNT-TFTs is stabilized. Flexible CMOS ring
      oscillators using such n-doped SWCNT-TFTs combined with the intrinsically p-type
      SWCNT-TFTs can generate a 0.2 Hz clock signal with significantly lower power
      consumption compared to similarly printed p-type only TFT based ring oscillators.
      Moving forward, this CMOS flexible ring oscillator can be practically used to
      develop fully printed inexpensive wireless sensor tags.

PMID- 27878196
TI  - Self-propelled round-trip motion of Janus particles in static line optical
      tweezers.
AB  - Controlled propulsion of microparticles and micromachines in fluids could
      revolutionize many aspects of technology, such as biomedicine, microfluidics,
      micro-mechanics, optomechanics, and cell biology. We report the self-propelled
      cyclic round-trip motion of metallo-dielectric Janus particles in static line
      optical tweezers (LOT). The Janus particle is a 5 MUm-diameter polystyrene sphere
      half-coated with 3 nanometer thick gold film. Both experiment and theory show
      that this cyclic translational and rotational motion is a consequence of the
      collective and fine action of the gold-face orientation dependent propulsion
      optical force, the gradient optical force, and the spontaneous symmetry breaking
      induced optical torque in different regions of the LOT. This study indicates a
      novel way to propel and manipulate the mechanical motion of microscopic motors
      and machines wirelessly in fluid, air, or vacuum environments using a static
      optical field with a smartly designed non-uniform intensity profile allowing
      fully controlled momentum and angular momentum exchange between light and the
      particle.

PMID- 27878197
TI  - An anti-ultrasonic-stripping effect in confined micro/nanoscale cavities and its
      applications for efficient multiscale metallic patterning.
AB  - We report a method to reliably and efficiently fabricate high-fidelity metallic
      structures from a ten-nanometer to a millimeter scale based on an anti-ultrasonic
      stripping (AUS) effect in confined micro/nanoscale cavities. With this AUS
      effect, metallic structures, which are surrounded by the pre-patterned closed
      templates, could be defined through selectively removing the evaporated metallic
      layer at the top and outside of the templates by ultrasonic-cavitation-induced
      stripping. Because only pre-patterned templates are required for exposure in this
      multiscale patterning process, this AUS-based process enables much smaller and
      more reliable plasmonic nanogaps due to the mitigated proximity effect and allows
      rapid fabrication of multiscale metallic structures which require both tiny and
      large structures. With unprecedented efficiency and resolution down to a ten
      nanometer scale, various metallic structures were fabricated using this AUS
      effect-based multiscale patterning process. This AUS effect paves the way for
      direct writing of metallic structures with a high resolution over a large area
      for practical applications in plasmonics and nanogap-based electronics.

PMID- 27878198
TI  - One pot synthesis of alpha-ketoamides from ethylarenes and amines: a metal free
      difunctionalization strategy.
AB  - One-pot and metal free synthesis of alpha-ketoamides has been described through
      in situ generation of aryl ketones from easily available ethylarenes followed by
      amidation with various amines. This multiple oxidation protocol involves
      catalytic I2-pyridine-TBHP (t-butyl hydroperoxide) mediated oxidative benzylic
      carbonylation and sequential NaI-TBHP mediated oxidative amidation without using
      any solvent.

PMID- 27878199
TI  - Sonochemical synthesis of highly branched flower-like Fe3O4@SiO2@Ag
      microcomposites and their application as versatile SERS substrates.
AB  - We report a novel strategy for the synthesis of magnetic-based flower-like silver
      composite microspheres (Fe3O4@SiO2@Ag microflowers) with a highly branched shell
      structure through a sonochemical-assisted method. The obtained Fe3O4@SiO2@Ag
      microflowers possess good dispersity, high magnetic responsiveness, and highly
      reproducible structures. The size and morphology of the silver petal shell of
      these microflowers can be easily controlled by varying the experimental
      parameters. The silver petal provides an effectively large surface area for
      forming sufficient plasmonic hot spots and capturing target molecules. The
      microscale magnetic core endows microflowers with superior magnetic nature to
      enrich targeted analytes and create abundant interparticle hot spots through
      magnetism-induced aggregation. Hence, Fe3O4@SiO2@Ag microflowers could be a
      versatile SERS substrate, as verified by the detection of the non-adsorbed R6G
      molecules and the adsorbed pesticide thiram, with a detection limit as low as 1 *
      10-14 M and 1 * 10-11 M, respectively. We further demonstrate that aptamer
      functionalized microflowers can easily capture S. aureus in tap water and
      significantly enhance their SERS signal. Moreover, the microflowers can be easily
      recycled because of the intrinsic magnetism of the Fe3O4 cores, which indicate a
      new route in eliminating the "single-use" problem of traditional SERS substrates.
      These advantages make the microflowers powerful SERS probes for chemical and
      biological analyses.

PMID- 27878200
TI  - Near-field Raman dichroism of azo-polymers exposed to nanoscale dc electrical and
      optical poling.
AB  - Azobenzene-functionalized polymer films are functional materials, where the
      (planar vs. homeotropic) orientation of azo-dyes can be used for storing data. In
      order to characterize the nanoscale 3D orientation of the pigments in sub-10 nm
      thick polymer films we use two complementary techniques: polarization-controlled
      tip-enhanced Raman scattering (TERS) microscopy and contact scanning capacity
      microscopy. We demonstrate that the homeotropic and planar orientations of the
      azo-dyes are produced by applying a local dc electrical field and a resonant
      longitudinal optical near-field, respectively. For a non-destructive probe of the
      azo-dye orientation we apply a non-resonant optical near-field and compare the
      intensities of the Raman-active vibrational modes. We show that near-field Raman
      dichroism, a characteristic similar to the absorption dichroism used in far-field
      optics, can be a quantitative indicator of the 3D molecular orientation of the
      azo-dye at the nanoscale. This study directly benefits the further development of
      photochromic near-field optical memory that can lead to ultrahigh density
      information storage.

PMID- 27878202
TI  - Presence of orally administered rice bran oil gamma-oryzanol in its intact form
      in mouse plasma.
AB  - Although the beneficial effects (e.g., lipid-lowering activity) of gamma-oryzanol
      (OZ), a mixture of ferulic acid esters of plant sterols and triterpene alcohols,
      have been extensively investigated, few studies have evaluated the absorption and
      metabolism of OZ. Moreover, it is unclear whether OZ, once ingested, is directly
      absorbed by the intestine into the bloodstream at a sufficient level to exhibit
      activity. Here, we prepared OZ concentrate from purified rice bran oil (Rice Oil
      OZ), determined the concentration of OZ in the preparation (cycloartenyl ferulate
      equivalent concentration; 52.2%), and then carried out chromatography-mass
      spectrometry analysis of plasma samples from mice after oral administration of
      Rice Oil OZ. The OZ concentrations of plasma from the control (vehicle-treated)
      mice were low (trace levels); however, at 5 h after a single oral administration
      of the Rice Oil OZ (600 mg per kg body weight), the levels significantly
      increased, reaching 17.6 ng mL-1 for cycloartenyl ferulate, 28.2 ng mL-1 for 24
      methylenecycloartanyl ferulate isomers, 15.6 ng mL-1 for campesteryl ferulate,
      and 5.1 ng mL-1 for beta-sitosteryl ferulate, respectively, expressed in
      equivalence of cycloartenyl ferulate in plasma. These results provided the first
      mass spectrometric evidence suggesting that a portion of orally administered OZ
      is directly absorbed by the intestine and is present in the intact form in
      plasma. The presence of a significant amount of OZ in its intact form in plasma
      may explain the beneficial effects of OZ in vivo.

PMID- 27878204
TI  - Continuous and ultrathin platinum films on graphene using atomic layer
      deposition: a combined computational and experimental study.
AB  - Integrating metals and metal oxides with graphene is key in utilizing its
      extraordinary material properties that are ideal for nanoelectronic and catalyst
      applications. Atomic layer deposition (ALD) has become a key technique for
      depositing ultrathin, conformal metal(oxide) films. ALD of metal(oxide) films on
      graphene, however, remains a genuine challenge due to the chemical inertness of
      graphene. In this study we address this issue by combining first-principles
      density functional theory (DFT) simulations with ALD experiments. The focus is on
      the Pt ALD on graphene, as this hybrid system is very promising for solar and
      fuel cells, hydrogen technologies, microreactors, and sensors. Here we elucidate
      the surface reactions underpinning the nucleation stage of Pt ALD on pristine,
      defective and functionalized graphenes. The employed reaction mechanism clearly
      depends on (a) the available surface groups on graphene, and (b) the ligands
      accompanying the metal centre in the precursor. DFT calculations also indicate
      that graphene oxide (GO) can afford a stronger adsorption of MeCpPtMe3, unlike
      Pt(acac)2, as compared to bare (non-functionalized) graphene, suggesting that GO
      monolayers are effective Pt ALD seed layers. Confirming the latter, we evince
      that wafer-scale, continuous Pt films can indeed be grown on GO monolayers using
      a thermal ALD process with MeCpPtMe3 and O2 gas. Besides, the current in-depth
      atomistic insights are of practical use for understanding similar ALD processes
      of other metals and metal oxides on graphene.

PMID- 27878208
TI  - The interaction of working length and plate strain.

PMID- 27878205
TI  - Iterative Development and Evaluation of a Pharmacogenomic-Guided Clinical
      Decision Support System for Warfarin Dosing.
AB  - OBJECTIVE: Pharmacogenomic-guided dosing has the potential to improve patient
      outcomes but its implementation has been met with clinical challenges. Our
      objective was to develop and evaluate a clinical decision support system (CDSS)
      for pharmacogenomic-guided warfarin dosing designed for physicians and
      pharmacists. METHODS: Twelve physicians and pharmacists completed 6 prescribing
      tasks using simulated patient scenarios in two iterations (development and
      validation phases) of a newly developed pharmacogenomic-driven CDSS prototype.
      For each scenario, usability was measured via efficiency, recorded as time to
      task completion, and participants' perceived satisfaction which were compared
      using Kruskal-Wallis and Mann Whitney U tests, respectively. Debrief interviews
      were conducted and qualitatively analyzed. Usability findings from the first
      (i.e. development) iteration were incorporated into the CDSS design for the
      second (i.e. validation) iteration. RESULTS: During the CDSS validation
      iteration, participants took more time to complete tasks with a median (IQR) of
      183 (124-247) seconds versus 101 (73.5-197) seconds in the development iteration
      (p=0.01). This increase in time on task was due to the increase in time spent in
      the CDSS corresponding to several design changes. Efficiency differences that
      were observed between pharmacists and physicians in the development iteration
      were eliminated in the validation iteration. The increased use of the CDSS
      corresponded to a greater acceptance of CDSS recommended doses in the validation
      iteration (4% in the first iteration vs. 37.5% in the second iteration, p<0.001).
      Overall satisfaction did not change statistically between the iterations but the
      qualitative analysis revealed greater trust in the second prototype. CONCLUSIONS:
      A pharmacogenomic-guided CDSS has been developed using warfarin as the test drug.
      The final CDSS prototype was trusted by prescribers and significantly increased
      the time using the tool and acceptance of the recommended doses. This study is an
      important step toward incorporating pharmacogenomics into CDSS design for
      clinical testing.

PMID- 27878207
TI  - Plasma-derived versus recombinant factor concentrates in PUPs: a never ending
      debate?
AB  - Inhibitor development in haemophilia is a serious complication to treatment with
      factor concentrates. Since the advent of more pure products, especially developed
      using recombinant DNA technology, some studies have shown an increased incidence
      of inhibitors in previously untreated patients (PUPs) receiving recombinant
      products whereas plasma-derived concentrates sometimes have been claimed to have
      a protective role, probably due to the content of von Willebrand factor (VWF). In
      fact, experiments indicate that the VWF may block uptake of factor VIII into
      macrophages for further processing to the immune system. Also, a competition
      between VWF and inhibitor binding to the C2 domain of factor VIII has been
      suggested. Recently, large cohort and surveillance studies have created a
      vigorous debate about the role of product class for inhibitor development as
      results have been conflicting. The only randomised prospective study, the SIPPET
      study, was published in 2016, and substantiated previous reports claiming that
      plasma derived concentrates give less inhibitors in patients with severe
      haemophilia A, previously not exposed to factor VIII. The debate will continue.

PMID- 27878206
TI  - New findings on venous thrombogenesis.
AB  - Venous thrombosis (VT) is the third most common cause of cardiovascular death
      worldwide. Complications from VT and pulmonary embolism are the leading cause of
      lost disability-adjusted life years. Risks include genetic (e.g., non-O blood
      group, activated protein C resistance, hyperprothrombinemia) and acquired (e.g.,
      age, surgery, cancer, pregnancy, immobilisation, female hormone use) factors.
      Pathophysiologic mechanisms that promote VT are incompletely understood, but
      involve abnormalities in blood coagulability, vessel function, and flow (so
      called Virchow's Triad). Epidemiologic studies of humans, animal models, and
      biochemical and biophysical investigations have revealed contributions from
      extrinsic, intrinsic, and common pathways of coagulation, endothelial cells,
      leukocytes, red blood cells, platelets, cell-derived microvesicles, stasis
      induced changes in vascular cells, and blood rheology. Knowledge of these
      mechanisms may yield new therapeutic targets. Characterisation of mechanisms that
      mediate VT formation and stability, particularly in aging, are needed to advance
      understanding of VT.

PMID- 27878209
TI  - Preclinical models of overwhelming sepsis implicate the neural system that
      encodes contextual fear memory.
AB  - Long-term sepsis survivors sustain cryptic brain injury that leads to cognitive
      impairment, emotional imbalance, and increased disability burden. Suitable animal
      models of sepsis, such as cecal ligation and puncture (CLP), have permitted the
      analysis of abnormal brain circuits that underlie post-septic behavioral
      phenotypes. For instance, we have previously shown that CLP-exposed mice exhibit
      impaired spatial memory together with depleted dendritic arbors and decreased
      spines in the apical dendrites of pyramidal neurons in the CA1 region of the
      hippocampus. Here we show that contextual fear conditioning, a form of
      associative memory for fear, is chronically disrupted in CLP mice when compared
      to SHAM-operated animals. We also find that the excitatory neurons in the
      basolateral nucleus of the amygdala (BLA) and the granule cells in the dentate
      gyrus (DG) display significantly fewer dendritic spines in the CLP group relative
      to the SHAM mice, although the dendritic arbors and gross morphology of the BLA
      and DG are comparable between the two groups. Moreover, the basal dendrites of
      CA1 pyramidal neurons are unaffected in the CLP mice. Taken together, our data
      indicate that the structural damage in the amygdalar-hippocampal network
      represents the neural substrate for impaired contextual fear memory in long-term
      sepsis survivors. Further, our data suggest that the brain injury caused by
      overwhelming sepsis alters the stability of the synaptic connections involved in
      associative fear. These results likely have implications for the emotional
      imbalance observed in human sepsis survivors.

PMID- 27878211
TI  - Liraglutide Enhances the Efficacy of Human Mesenchymal Stem Cells in Preserving
      Islet beta-cell Function in Severe Non-obese Diabetic Mice.
AB  - Glucagon-like peptide 1 (GLP-1) can promote islet beta-cell replication and
      function, and mesenchymal stem cells (MSCs) can inhibit T cell autoimmunity. This
      study aimed at testing the dynamic distribution of infused human MSCs and
      therapeutic effect of combined MSCs and Liraglutide, a long-acting GLP-1
      analogue, on preserving beta-cell function in severe non-obese diabetic (NOD)
      mice. We found that infused MSCs accumulated in the pancreas at 4 weeks post
      infusion, which was not affected by Liraglutide treatment. Liraglutide
      significantly enhanced the function of MSCs to preserve islet beta-cells by
      reducing glucose level at 30 minutes post glucose challenge and increasing the
      contents and secretion of insulin by islet beta-cells in severe diabetic NOD
      mice. Infusion with MSCs significantly reduced insulitis scores, but increased
      the frequency of splenic Tregs, accompanied by reducing the levels of plasma IFN
      gamma and TNF-alpha and elevating the levels of plasma IL-10 and transforming
      growth factor-beta1 (TGF-beta1) in NOD mice. Although Liraglutide mitigated MSC
      mediated changes in the frequency of Tregs and the levels of plasma IL-10,
      Liraglutide significantly increased the levels of plasma TGF-beta1 in severe
      diabetic NOD mice. Therefore, our findings suggest that Liraglutide may enhance
      the therapeutic efficacy of MSCs in treatment of severe type 1 diabetes.

PMID- 27878210
TI  - T regulatory cell mediated immunotherapy for solid organ transplantation: A
      clinical perspective.
AB  - T regulatory cells (Tregs) play a vital role in suppressing heightened immune
      responses, and thereby promote a state of immunological tolerance. Tregs modulate
      both innate and adaptive immunity, which make them a potential candidate for cell
      based immunotherapy to suppress uncontrolled activation of graft specific
      inflammatory cells and their toxic mediators. These grafts specific inflammatory
      cells (T effector cells) and other inflammatory mediators (Immunoglobulins,
      active complement mediators) are mainly responsible for graft vascular
      deterioration followed by acute/chronic rejection. Treg mediated immunotherapy is
      under investigation to induce allospecific tolerance in various ongoing clinical
      trials in organ transplant recipients. Treg immunotherapy is showing promising
      results but the key issues regarding Treg immunotherapy are not yet fully
      resolved including their mechanism of action, and specific Treg cell phenotype
      responsible for a state of tolerance. This review highlights the involvement of
      various subsets of Tregs during immune suppression, novelty of Tregs functions,
      effects on angiogenesis, emerging technologies for effective Treg expansion,
      plasticity and safety associated with clinical applications. Altogether this
      information will assist in designing single/combined Treg mediated therapies for
      successful clinical trials in solid organ transplantations.

PMID- 27878212
TI  - Obesity paradox, obesity orthodox, and the metabolic syndrome: An approach to
      unity.
AB  - Obesity and the accompanying metabolic syndrome are strongly associated with
      heightened morbidity and mortality in older adults. In our review of more than 20
      epidemiologic studies of major infectious diseases, including leaders such as
      tuberculosis, community-acquired pneumonia, and sepsis, obesity was associated
      with better outcomes. A cause-and-effect relationship between over-nutrition and
      survival with infection is suggested by results of two preliminary studies of
      infections in mice, where high fat feeding for 8-10 weeks provided much better
      outcomes. The better outcomes of infections with obesity are reminiscent of many
      recent studies of "sterile" non-infectious medical and surgical conditions where
      outcomes for obese patients are better than for their thinner counterparts ---
      and given the tag "obesity paradox". Turning to the history of medicine and
      biological evolution, we hypothesize that the metabolic syndrome has very ancient
      origins and is part of a lifelong metabolic program. While part of that program
      (the metabolic syndrome) promotes morbidity and mortality with aging, it helps
      infants and children as well as adults in their fight against infections and
      recovery from injuries, key roles in the hundreds of centuries before the public
      health advances of the 20th century. We conclude with speculation on how
      understanding the biological elements that protect obese patients with infections
      or injuries might be applied advantageously to thin patients with the same
      medical challenges.

PMID- 27878213
TI  - Holocene paleo-sea level changes along the coast of Rio de Janeiro, southern
      Brazil: Comment on Castro et al. (2014).
AB  - The present work discusses and reinterprets paleo-sea level indicators used to
      build Holocene sea-level curve for the coast of Rio de Janeiro at former works.
      We conclude that: (a) the paleo-sea levels inferred by vermetid remains show that
      sea-level has fallen over the past 4400 years, at least; (b) the paleo-sea level
      inferred by the beachrock facies and dated shells of Jacone shows that sea-level
      was near the present elevation between 8198 and 5786 years before present; and
      (c) several shells from other beachrocks were deposited probably thousands of
      years after the specimens died and consequently do not allow precise
      reconstructions of paleo-sea levels. These conclusions differ from the
      conclusions of the original paper.

PMID- 27878215
TI  - International collaboration in the Nursing agenda in the coming decades.

PMID- 27878214
TI  - Lethal and sublethal effects of essential oil of Lippia sidoides (Verbenaceae)
      and monoterpenes on Chagas' disease vector Rhodnius prolixus.
AB  - The aim of this study was to identify the composition of the essential oil from
      leaves of Lippia sidoides (EOLS), a typical shrub commonly found in the dry
      northeast of Brazil, popularly known as "alecrim-pimenta". Additionally, we
      investigated the nymphicidal, ovicidal, phagoinhibitory and excretion effects of
      EOLS, its major constituent thymol and its isomer carvacrol, on fourth instar
      nymphs and eggs of Rhodnius prolixus, the Chagas' disease vector. The nymphicidal
      and ovicidal activity of thymol, carvacrol, and EOLS was assessed by tests using
      impregnated Petri dishes. The lethal concentration values (LC50) for EOLS,
      carvacrol, and thymol were 54.48, 32.98, and 9.38 mg/cm2, respectively. The
      ovicidal test showed that both carvacrol and thymol (50 mg/cm2) inhibited
      hatching (50% and 23.3%, respectively), while treatments with 10 mg/cm2 or 50
      mg/cm2 EOLS did not affect the hatching rate at all (80% and 90%, respectively).
      We observed an anti-feeding effect in insects fed with blood containing natural
      products at the higher concentrations (100 ug/mL). Finally, excretion rate was
      affected by EOLS and carvacrol, but not by thymol. These findings offer novel
      insights into basic physiological processes that make the tested natural
      compounds interesting candidates for new types of insecticides.

PMID- 27878216
TI  - Quality of nursing documentation before and after the Hospital Accreditation in a
      university hospital.
AB  - Objective: to analyze the quality of nursing documentation by comparing the
      periods before and after the preparation for the hospital accreditation, using
      the Quality of Nursing Diagnoses, Interventions and Outcomes - Brazilian version
      (Q-DIO- Brazilian version). Method: observational study of interventions
      conducted in a university hospital. Nursing documentation of 112 medical records
      for the period before and 112 for the period after the hospital accreditation
      were compared using the Q-DIO instrument - Brazilian version. Data were
      statistically analyzed. Results: there was a significant improvement in the
      quality of nursing documentation. When the total score of the instrument was
      evaluated, a significant improvement was observed in 24 out of the 29 items
      (82.8%). Conclusion: there was commitment to the shift of culture by means of the
      interventions carried out, which resulted in the conquest of the quality seal
      ensured by the Joint Commission International.

PMID- 27878217
TI  - Factors associated with young adults' knowledge regarding family history of
      Stroke.
AB  - Objective:: to analyze the factors associated with young adults' knowledge
      regarding family history of stroke. Method:: an analytical transversal study,
      with 579 young adults from state schools, with collection of sociodemographic,
      clinical and risk factor-related variables, analyzed using logistic regression
      (backward elimination). Results:: a statistical association was detected between
      age, civil status, and classification of arterial blood pressure and abdominal
      circumference with knowledge of family history of stroke. In the final logistic
      regression model, a statistical association was observed between knowledge
      regarding family history of stroke and the civil status of having a partner
      (ORa=1.61[1.07-2.42]; p=0.023), abdominal circumference (ORa=0.98[0.96-0.99];
      p=0.012) and normal arterial blood pressure (ORa=2.56[1.19-5.52]; p=0.016).
      Conclusion:: an association was observed between socioeconomic factors and risk
      factors for stroke and knowledge of family history of stroke, suggesting the need
      for health education or even educational programs on this topic for the clientele
      in question. Objetivo:: analisar os fatores associados ao conhecimento dos
      adultos jovens sobre historico familiar de Acidente Vascular Cerebral (AVC).
      Metodo:: estudo transversal analitico, com 579 adultos jovens de escolas
      publicas, com coleta de variaveis sociodemograficas, clinicas e de fatores de
      risco em formulario, analisados utilizando-se regressao logistica (backward
      elimination). Resultados:: detectou-se associacao estatistica de idade, situacao
      conjugal, classificacao da pressao arterial e circunferencia abdominal com
      conhecimento do historico familiar de AVC. No modelo final de regressao
      logistica, observou-se associacao estatistica do conhecimento sobre historico
      familiar de AVC com situacao conjugal com companheiro (ORa=1,61[1,07-2,42];
      p=0,023), circunferencia abdominal (ORa=0,98[0,96-0,99]; p=0,012) e pressao
      arterial normal (ORa=2,56[1,19-5,52]; p=0,016). Conclusao:: foi constatada
      associacao de fatores socioeconomicos e de risco para AVC com o conhecimento do
      historico familiar de AVC, sugerindo a necessidade de educacao em saude ou mesmo
      de programas educacionais sobre o tema junto a clientela em estudo. Objetivo::
      analizar los factores asociados al conocimiento de los adultos jovenes sobre el
      historico familiar de Accidente Vascular Cerebral (AVC). Metodo:: estudio
      transversal analitico en 579 adultos jovenes de escuelas publicas, con
      recoleccion de variables sociodemograficas, clinicas y de factores de riesgo en
      formulario, los datos fueron analizados utilizando la regresion logistica
      (backward elimination). Resultados:: se detecto asociacion estadistica de edad,
      situacion conyugal, clasificacion de la presion arterial y circunferencia
      abdominal con el conocimiento del historico familiar de AVC. En el modelo final
      de regresion logistica, se observo una asociacion estadistica del conocimiento
      sobre el historico familiar de AVC con: situacion conyugal con companero
      (ORa=1,61[1,07-2,42] p=0,023); circunferencia abdominal (ORa=0,98[0,96-0,99]
      p=0,012); y presion arterial normal (ORa=2,56[1,19-5,52] p=0,016). Conclusion::
      fue constatada asociacion de factores socioeconomicos y de riesgo para AVC con el
      conocimiento del historico familiar de AVC; se sugiere la necesidad de realizar
      acciones de educacion en salud o inclusive de preparar programas educacionales
      sobre el tema para la poblacion estudiada.

PMID- 27878218
TI  - Nursing care missed in patients at risk of or having pressure ulcers.
AB  - Objective: to determine the nursing care missed as perceived by the nursing staff
      and its relation with the nursing care missed identified in the assessment of
      patients at risk of or having pressur ulcers. Method: descriptive correlation
      study. The participants were 161 nurses and 483 patients from a public hospital.
      The MISSCARE survey was used in combination with a Nursing Care Assessment Form
      for Patients at Risk of or having pressure ulcers. For the analysis, descriptive
      and inferential statistics were used. Results: the nursing staff indicated
      greater omission in skin care (38.5%), position change (31.1%) and the
      registration of risk factors for the development of pressure ulcers (33.5%). The
      nursing care missed identified in the assessment related to the use of pressure
      relief on bony prominences and drainage tubes interfering in the patient's
      movements (both with 58.6%) and the use of pneumatic mattresses (57.6%).
      Conclusion: a high percentage of nursing care missed was found according to the
      staff's perception. Nevertheless, the assessment of the nursing care missed was
      much higher. No significant relation was found between both. Therefore, it is a
      priority to reflect on the importance of objective patient assessments.

PMID- 27878219
TI  - Financial impact of nursing professionals staff required in an Intensive Care
      Unit.
AB  - Objective: to calculate the cost of the average time of nursing care spent and
      required by patients in the Intensive Care Unit (ICU) and the financial expense
      for the right dimension of staff of nursing professionals. Method: a descriptive,
      quantitative research, using the case study method, developed in adult ICU
      patients. We used the workload index - Nursing Activities Score; the average care
      time spent and required and the amount of professionals required were calculated
      using equations and from these data, and from the salary composition of
      professionals and contractual monthly time values, calculated the cost of direct
      labor of nursing. Results: the monthly cost of the average quantity of available
      professionals was US$ 35,763.12, corresponding to 29.6 professionals, and the
      required staff for 24 hours of care is 42.2 nurses, with a monthly cost of US$
      50,995.44. Conclusion: the numerical gap of nursing professionals was 30% and the
      monthly financial expense for adaptation of the structure is US$ 15,232.32, which
      corresponds to an increase of 42.59% in the amounts currently paid by the
      institution.

PMID- 27878220
TI  - Diagnosis of compliance of health care product processing in Primary Health Care.
AB  - Objective: identify the compliance of health care product processing in Primary
      Health Care and assess possible differences in the compliance among the services
      characterized as Primary Health Care Service and Family Health Service. Method:
      quantitative, observational, descriptive and inferential study with the
      application of structure, process and outcome indicators of the health care
      product processing at ten services in an interior city of the State of Sao Paulo 
      Brazil. Results: for all indicators, the compliance indices were inferior to the
      ideal levels. No statistically significant difference was found in the indicators
      between the two types of services investigated. The health care product cleaning
      indicators obtained the lowest compliance index, while the indicator technical
      operational resources for the preparation, conditioning,
      disinfection/sterilization, storage and distribution of health care products
      obtained the best index. Conclusion: the diagnosis of compliance of health care
      product processing at the services assessed indicates that the quality of the
      process is jeopardized, as no results close to ideal levels were obtained at any
      service. In addition, no statistically significant difference in these indicators
      was found between the two types of services studied.

PMID- 27878221
TI  - The use of a metronome during cardiopulmonary resuscitation in the emergency room
      of a university hospital.
AB  - Objective: to compare the rate of return of spontaneous circulation (ROSC) and
      death after cardiac arrest, with and without the use of a metronome during
      cardiopulmonary resuscitation (CPR). Method: case-control study nested in a
      cohort study including 285 adults who experienced cardiac arrest and received CPR
      in an emergency service. Data were collected using In-hospital Utstein Style. The
      control group (n=60) was selected by matching patients considering their
      neurological condition before cardiac arrest, the immediate cause, initial arrest
      rhythm, whether epinephrine was used, and the duration of CPR. The case group
      (n=51) received conventional CPR guided by a metronome set at 110 beats/min. Chi
      square and likelihood ratio were used to compare ROSC rates considering p<=0.05.
      Results: ROSC occurred in 57.7% of the cases, though 92.8% of these patients died
      in the following 24 hours. No statistically significant difference was found
      between groups in regard to ROSC (p=0.2017) or the occurrence of death
      (p=0.8112). Conclusion: the outcomes of patients after cardiac arrest with and
      without the use of a metronome during CPR were similar and no differences were
      found between groups in regard to survival rates and ROSC.

PMID- 27878222
TI  - Microbiological evaluation of the steam sterilization of assembled laparoscopic
      instruments.
AB  - Objective: assess the safety of steam sterilization of assembled laparoscopic
      instruments with challenge contamination. Method: a laboratory experimental
      study, using as test samples trocars and laparoscopic graspers. Geobacillus
      stearothermophillus ATCC-7953 was used, with a microbial population of
      106UFC/Filter paper substrate, removed from the biological indicator. Three of
      them were introduced into each instrument at the time of assembly, and sterilized
      at pressurized saturated steam, 134oC for 5 minutes. After sterilization, the
      instrument was disassembled and each filter paper substrate was inoculated in
      soybean casein culture and incubated at 56oC for 21 days. In case of absence of
      growth, they were subjected to heat shock of 80oC, for 20 minutes and re
      incubated for 72 hours. Sample size: 185 graspers and 185 trocars, with 95%
      power. We paired the experiments with comparative negative control groups (5
      graspers and 5 trocars with challenge contamination, sterilized disassembled) and
      positive control (30 filter paper supports, unsterilized), subject to the same
      incubation procedures. Results: there was no microbial growth in experimental and
      negative control. The results of the positive control were satisfactory.
      Conclusion: this study provided strong scientific evidence to support the safety
      of steam sterilizing of the assembled laparoscopic instrument.

PMID- 27878223
TI  - Experimental study with nursing staff related to the knowledge about pressure
      ulcers.
AB  - Objective: to compare the scores of knowledge in teams participating or not
      participating in educational interventions about pressure ulcers. Method: a
      quantitative study with experimental design. Data were collected through a
      validated questionnaire. The study included 71 individuals, including nurses and
      nursing technicians from three intensive care units, divided into intervention
      group and control group. Data analysis considered the scores of the groups in the
      moment before and after intervention. To check the average rate of correct
      answers, we calculated the mean and standard deviation. We carried out the Mann
      Whitney test for analysis of two independent samples, and the Wilcoxon test for
      related samples. Results: The mean percentage of correct answers, at the baseline
      was 74.1% (SD = 26.4) in the intervention group and 76.0% (SD = 22.9) in the
      control group and post time -intervention, was 87.8% (SD = 18.8) in the group
      receiving educational intervention, considering that in the control group it was
      79.1% (SD = 22.2). The group that participated in educational interventions did
      not reach the proper average of 90% correct answers for the test. Conclusion:
      educational interventions on staging, evaluation and prevention of pressure
      ulcers contributed significantly to the increase of correct responses score in
      the knowledge test of the intervention group and improved their knowledge on the
      subject.

PMID- 27878225
TI  - ?

PMID- 27878224
TI  - Potential drug interactions in patients given antiretroviral therapy.
AB  - Objective: to investigate potential drug-drug interactions (PDDI) in patients
      with HIV infection on antiretroviral therapy. Methods: a cross-sectional study
      was conducted on 161 adults with HIV infection. Clinical, socio demographic, and
      antiretroviral treatment data were collected. To analyze the potential drug
      interactions, we used the software Micromedex(r). Statistical analysis was
      performed by binary logistic regression, with a p-value of <=0.05 considered
      statistically significant. Results: of the participants, 52.2% were exposed to
      potential drug-drug interactions. In total, there were 218 potential drug-drug
      interactions, of which 79.8% occurred between drugs used for antiretroviral
      therapy. There was an association between the use of five or more medications and
      potential drug-drug interactions (p = 0.000) and between the time period of
      antiretroviral therapy being over six years and potential drug-drug interactions
      (p < 0.00). The clinical impact was prevalent sedation and cardiotoxicity.
      Conclusions: the PDDI identified in this study of moderate and higher severity
      are events that not only affect the therapeutic response leading to toxicity in
      the central nervous and cardiovascular systems, but also can interfere in tests
      used for detection of HIV resistance to antiretroviral drugs.

PMID- 27878226
TI  - Psychometric properties of Multidimensional Health Locus of Control - A and
      General Self-Efficacy Scale in civil servants: ELSA-Brasil Musculoskeletal Study
      (ELSA-Brasil MSK).
AB  - Background: Health-related control and self-efficacy beliefs can be assessed in
      the general population using Multidimensional Health Locus of Control-A subscales
      (MHLC-A) and the General Self-Efficacy Scale (GSES), respectively. Objective: To
      test construct validity, internal consistency, reliability (test-retest) and
      ceiling and floor effects of Portuguese-Brazil versions of MHLC-A and GSES.
      Method: Civil servants (N=2901) enrolled in a large Brazilian cohort were
      included. A new version of the GSES was produced (GSES-Brazil). Procedures for
      cross-cultural adaptation and testing of psychometric properties followed well
      accepted international guidelines. Results: Confirmatory factor analyses yielded
      the following indices: MHLC-A (tridimensional model): chi2[df]=223.45[132], p
      value <0.01; CFI=0.87; TLI=0.85; RMSEA=0.07 (0.07-0.08); WRMR=3.00. GSES-Brazil
      (unidimensional model): chi2[df]=788.60[35], p-value <0.01; CFI=0.95; TLI=0.94;
      RMSEA=0.09 (0.08-0.09); WRMR=2.50. Cronbach's alpha coefficients and Intraclass
      Correlation Coefficients (ICC2,1) ranged from 0.57 (0.54-0.59) and 0.57 (0.47
      0.65) for MHLC-A internality to 0.80 (0.79-0.81) and 0.71 (0.66-0.77) for GSES
      Brazil, respectively. There was no evidence of ceiling and floor effects.
      Convergent validity analyses provided further support for construct validity of
      both scales. Conclusion: These findings support the use of the newly developed
      version of GSES-Brazil for the assessment of general self-efficacy of adult
      Brazilians. Internal consistency was lower than ideal for MHLC-A, indicating
      these subscales may need further refinements to provide a more psychometrically
      sound measure of control beliefs.

PMID- 27878227
TI  - Cardiovascular coupling during graded postural challenge: comparison between
      linear tools and joint symbolic analysis.
AB  - Background: A joint symbolic analysis (JSA) is applied to assess the strength of
      the cardiovascular coupling from spontaneous beat-to-beat variability of the
      heart period (HP) and the systolic arterial pressure (SAP) during an experimental
      protocol inducing a gradual baroreflex unloading evoked by postural change (i.e.
      graded head-up tilt). Method:: The adopted JSA can quantify the degree of
      association between the HP and SAP variabilities as a function of the time scale
      of the HP and SAP patterns. Traditional linear tools assessing the HP-SAP
      coupling strength, such as squared correlation coefficient, squared coherence
      function, and percentage of baroreflex sequences, were computed as well for
      comparison. Results:: We found that: i) JSA indicated that the strength of the
      cardiovascular coupling at slow temporal scales gradually increased with the
      magnitude of the orthostatic challenge, while that at fast temporal scales
      gradually decreased; ii) the squared correlation coefficient and percentage of
      baroreflex sequences did not detect this behavior; iii) even though squared
      coherence function could measure the magnitude of the HP-SAP coupling as a
      function of the time scale, it was less powerful than JSA owing to the larger
      dispersion of the frequency domain indexes. Conclusion:: Due to its peculiar
      features and high statistical power, JSA deserves applications to pathological
      groups in which the link between HP and SAP variabilities is lost or decreased
      due to the overall depression or impairment of the cardiovascular control.

PMID- 27878228
TI  - Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado
      Joseph disease.
AB  - Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an
      autosomal dominant neurodegenerative disorder caused by expansion of the
      polyglutamine domain of the ataxin-3 (ATX3) protein. MJD/SCA3 is the most
      frequent autosomal dominant ataxia in many countries. The mechanism underlying
      MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation
      leading to neuronal dysfunction followed by cell death. Currently, there are no
      effective treatments for patients with MJD/SCA3. Here, we report on the potential
      use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the
      expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT
      assay and by flow cytometry after staining with annexin V-FITC/propidium iodide.
      Treatment with lithium carbonate and coenzyme Q10 led to a significant increase
      in viability of cells expressing expanded ATX3 (Q84). In addition, we found that
      the increase in cell viability resulted from a significant reduction in the
      proportion of apoptotic cells. Furthermore, there was a significant change in the
      expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10
      treatment, with an increase in the monomer fraction and decrease in aggregates.
      The safety and tolerance of both drugs are well established; thus, our results
      indicate that lithium carbonate and coenzyme Q10 are good candidates for further
      in vivo therapeutic trials.

PMID- 27878230
TI  - Rapid and sensitive detection of Plesiomonas shigelloides by cross-priming
      amplification of the hugA gene.
AB  - Plesiomonas shigelloides (P. shigelloides) is implicated as an aetiological agent
      of human gastroenteritis in humans, for which reliable laboratory detection of P.
      shigelloides is clinically and epidemiologically desirable. A simple molecular
      method for rapid detection of P. shigelloides using cross-priming amplification
      (CPA) has been developed, with hugA as the target. The hugA gene is required for
      haem iron utilisation and is critical for the survival and growth of P.
      shigelloides. The assay output was visualised as a colour change with no need to
      open the reaction tubes, and no false-positive results were detected for the 33
      non- P. shigelloides strains examined to assess assay specificity. The limit of
      detection was 200 fg P. shigelloides DNA per reaction and 3x103 CFU per g in
      human stools, which was 100 and 10-fold more sensitive than polymerase chain
      reaction, respectively. The CPA method was used to detect the presence of P.
      shigelloides in stool specimens from 70 patients with diarrhoea and 30
      environmental water samples, with no difference in accuracy between the CPA assay
      and the biological culture. The present study, therefore, suggests that the P.
      shigelloides hugA CPA assay may represent a valuable tool for rapid and sensitive
      detection of P. shigelloides in primary care facilities and clinical
      laboratories.

PMID- 27878231
TI  - SIRT1 exerts neuroprotective effects by attenuating cerebral ischemia/reperfusion
      induced injury via targeting p53/microRNA-22.
AB  - The aim of this study was to investigate whether the SIRT1 exerts neuroprotective
      effects by attenuating cerebral ischemia/reperfusion-induced injury (CIRI) via
      targeting p53/microRNA-22. We found that the overexpression of sirtuin 1 (SIRT1)
      decreased the infarct volume, suppressed p53 protein expression and activated
      microRNA-22 expression following CIRI. An injection of lipopolysaccharide (LPS, 1
      mg/ml; Sigma, St. Louis, MO USA) into the corpus callosum was used to induce CIRI
      in rats. The infarct volume and neurological deficit score were used to examine
      the effects of SIRT1 on CIRI. Furthermore, the overexpression of SIRT1 was found
      to suppress caspase-3 activity, inhibit the activation of the Bax signaling
      pathway, reduce tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6)
      activity, decrease cyclooxygenase (COX)-2 and inducible nitric oxide synthase
      (iNOS) protein expression, and increase IL-10 activity following CIRI. Following
      the downregulation of SIRT1, p53 protein expression was significantly increased,
      microRNA-22 expression was inhibited, caspase-3 activity was increased and the
      Bax signaling pathway was activated. In addition, the activity of TNF-alpha and
      IL-6 was was enhanced, COX-2 and iNOS protein expression was increased, and IL-10
      activity was reduced following CIRI. Thus, the data from our study suggest that
      SIRT1 attenuates CIRI by targeting the p53/microRNA-22 axix, while suppressing
      apoptosis, inflammation, COX-2 and iNOS expression.

PMID- 27878229
TI  - Glucagon-like peptide 1 improves insulin resistance in vitro through anti
      inflammation of macrophages.
AB  - Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment
      of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti
      inflammatory activity. Chronic inflammation in the adipose tissue of obese
      individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1
      analogue therapy in patients with T2D could suppress the inflammatory response of
      macrophages, and therefore inhibit insulin resistance. Our results showed that
      GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also
      inhibited the macrophage secretion of inflammatory cytokines including TNF-beta,
      IL-6, and IL-1beta. Furthermore, we observed that lipopolysaccharide (LPS)
      induced macrophage conditioned media could impair insulin-stimulated glucose
      uptake. This effect was compensated by treatment with the conditioned media from
      macrophages treated with the combination of LPS and exendin-4. It was also
      observed that exendin-4 directly inhibited the activation of NF-kappaB in
      macrophages. In conclusion, our results indicated that GLP-1 improved
      inflammatory macrophage-derived insulin resistance by inhibiting NF-kappaB
      pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our
      observations suggested that the anti-inflammatory effect of GLP-1 on macrophages
      can contribute to GLP-1 analogue therapy of T2D.

PMID- 27878232
TI  - Involvement of bleomycin hydrolase and poly(ADP-ribose) polymerase-1 in Ubc9
      mediated resistance to chemotherapy agents.
AB  - Ubiquitin-conjugating protein 9 (Ubc9), the sole enzyme for sumoylation, plays
      critical roles in many physiological functions, such as DNA damage repair and
      genome integrity. Its overexpression led to poor prognosis and drug resistance in
      tumor chemotherapy. However, the underlying mechanism by which Ubc9 promotes
      tumor progress and influences the susceptibility to antitumor agents remains
      elusive. In this study, we used nine antitumor agents with distinct actions to
      explore Ubc9-mediated resistance in human breast carcinoma MCF-7 cells. Increase
      of susceptibility, respectively, to boningmycin, hydroxycamptothecine, cis
      dichlorodiamineplatinum, 5-fluorouracil, vepeside and gemcitabine, but not for
      doxorubicin, vincristine and norcantharidin, was observed after the knockdown of
      Ubc9 protein level with RNA interference. Reduction of bleomycin hydrolase and
      poly(ADP-ribose) polymerase-1 levels after knockdown of Ubc9 suggests their
      contribution to Ubc9-mediated drug resistance. This is the first report on the
      sensitivity to hydroxycamptothecine, cis-dichlorodiamineplatinum and gemcitabine
      that increased after knockdown of bleomycin hydrolase at protein level. In
      conclusion, Ubc9 plays different roles of action in antitumor agents in
      chemotherapy. The process requires bleomycin hydrolase and poly(ADP-ribose)
      polymerase-1. The results are beneficial to deeply understanding of Ubc9
      functions and for precise prediction of chemotherapy outcomes in tumors.

PMID- 27878234
TI  - Prometastatic mechanisms of CAF-mediated EMT regulation in pancreatic cancer
      cells.
AB  - Tumor metastasis are accompanied by the EMT (epithelial-mesenchymal transition)
      MET (mesenchymal-epithelial transition) two-step process. In this study, we
      investigated the importance of cancer associated fibroblasts (CAF) in the
      process. First, the primary cultures of isolated pancreatic CAF, fibroblasts of
      normal pancreatic tissues (NF), and normal hepatic stellate cells (HSF) were
      identified and verified via the expression of alpha-SMA and vimentin. Using an
      indirect three-dimensional co-culture model, the morphological changes were
      observed by light microscopy and laser scanning confocal microscopy. The invasive
      and migration capacity of pancreatic cancer cells was determined by Transwell
      chamber migration assay or scratch assay. The mRNA and protein expression levels
      of E-cadherin, vimentin, and Gli1 were determined by RT-PCR and western blotting.
      Primary cultures of isolated CAF, NF, HSF showed satisfactory growth with active
      proliferation. Indirect co-culture with CAF, BxPc-3 and Panc-1 cells showed
      significant partial EMT, reduced E-cadherin expression, and enhanced vimentin
      expression as compared with the single culture and NF/HSF co-culture groups, with
      corresponding increases in migratory and invasive capacities. PCR and western
      blotting results showed that mRNA and protein expression levels of Gli1 in CAF
      and Snail in cancer cells were increased. This process could be reversed by
      inhibition of hedgehog (HH) signaling in CAF. In the tumor microenvironment,
      activation of CAF is the key event in mediating partial EMT, and its mechanism
      may be associated with paracrine action after activation of HH signaling in CAF.

PMID- 27878233
TI  - Benzoquinone from Fusarium pigment inhibits the proliferation of estrogen
      receptor-positive MCF-7 cells through the NF-kappaB pathway via estrogen receptor
      signaling.
AB  - Natural pigments are known for possessing a wide range of pharmacological and
      health-promoting properties. The pigments, produced by a new strain Fusarium
      (Fusarium sp. JN158) previously identified in our laboratory, were found to have
      6 peaks (representing 6 compounds) by high-performance liquid chromatography with
      a diode-array detector (HPLC-DAD) separation. The 6th peak compound (compound VI)
      is a benzoquinone compound. In this study, we examined the effects of compound VI
      on the proliferation of breast cancer cells and aimed to elucidate the underlying
      mechamisms. Compound VI exerted anti-proliferative effects on MCF-7 estrogen
      receptor (ER)+ cells in a dose-dependent manner (IC25, 7 uM; IC50, 11 uM),
      whereas it had no effect on MDA-MB-231 ER- cells and normal cells. The cell index
      (CI) began to decrease at 24 h following treatment with benzoquinone.
      Mechanistically, the results from molecular analysis revealed that compound VI
      inhibited the expression of ERalpha, progesterone receptor (PR), vascular
      endothelial growth factor (VEGF), Bcl-2, cyclin D1 and nuclear factor-kappaB (NF
      kappaB) p65, while it increased the expression of cleaved caspase-3 and Bax in
      the MCF-7 cells. Taken together, our findings indicate that compound VI exerts
      anti-proliferative effects on MCF-7 cells through the NF-kappaB pathway via the
      regulation of ER signaling. Our data may indicate that benzoquinone from Fusarium
      pigment may have potential for use as an anti-proliferative agent in the
      treatment of breast cancer.

PMID- 27878235
TI  - Accelerated cell cycle progression of human regulatory T cell-like cell line
      caused by continuous exposure to asbestos fibers.
AB  - Asbestos exposure causes malignant tumors such as lung cancer and malignant
      mesothelioma. Based on our hypothesis in which continuous exposure to asbestos of
      immune cells cause reduction of antitumor immunity, the decrease of natural
      killer cell killing activity with reduction of NKp46 activating receptor
      expression, inhibition of cytotoxic T cell clonal expansion, reduced CXCR3
      chemokine receptor expression and production of interferon-gamma production in
      CD4+ T cells were reported using cell line models, freshly isolated peripheral
      blood immune cells from health donors as well as asbestos exposed patients such
      as pleural plaque and mesothelioma. In addition to these findings, regulatory T
      cells (Treg) showed enhanced function through cell-cell contact and increased
      secretion of typical soluble factors, interleukin (IL)-10 and transforming growth
      factor (TGF)-beta, in a cell line model using the MT-2 human polyclonal T cells
      and its sublines exposed continuously to asbestos fibers. Since these sublines
      showed a remarkable reduction of FoxO1 transcription factor, which regulates
      various cell cycle regulators in asbestos-exposed sublines, the cell cycle
      progression in these sublines was examined and compared with that of the original
      MT-2 cells. Results showed that cyclin D1 expression was markedly enhanced, and
      various cyclin-dependent kinase-inhibitors were reduced with increased S phases
      in the sublines. Furthermore, the increase of cyclin D1 expression was regulated
      by FoxO1. The overall findings indicate that antitumor immunity in asbestos
      exposed individuals may be reduced in Treg through changes in the function and
      volume of Treg.

PMID- 27878238
TI  - Nobiletin attenuates lipopolysaccharide/D-galactosamine-induced liver injury in
      mice by activating the Nrf2 antioxidant pathway and subsequently inhibiting NF
      kappaB-mediated cytokine production.
AB  - Inflammation and oxidative stress serve an important role in the development of
      lipopolysaccharide/D-galactosamine (LPS/GalN)-induced acute liver injury.
      Nobiletin, which is found in high quantities in the peel of citrus fruits, is
      able to modulate immune responses, including inflammatory response and oxidative
      stress. The present study aimed to evaluate the protective effects of nobiletin
      on LPS/GalN-induced acute liver injury. Male C57BL/6 mice were intraperitoneally
      treated with nobiletin (50, 100 and 200 mg/kg) 2 h prior to LPS/GalN injection.
      Liver injury was observed in the LPS/GalN group, as demonstrated by increased
      levels of serum hepatic enzymes and hepatic inflammatory mediators, as well as by
      histopathological alterations. Treatment with nobiletin reduced serum alanine
      aminotransferase and aspartate aminotransferase levels, improved hepatic
      structure, and suppressed hepatic interleukin (IL)-1beta, IL-6 and tumor necrosis
      factor-alpha production 24 h after LPS/GalN exposure. Western blot analysis
      revealed that nobiletin treatment inhibited inducible nitric oxide synthase and
      cyclooxygenase-2 liver expression. In addition, nobiletin suppressed LPS/GalN
      induced phosphorylation and degradation of inhibitor of nuclear factor (NF)
      kappaB (IkappaB)alpha, as well as NF-kappaB p65 translocation into the nucleus.
      Nobiletin also upregulated the expression of nuclear NF-E2-related factor 2
      (Nrf2) and cytoplasmic heme oxygenase-1. In conclusion, these results indicate
      that nobiletin serves a protective role in LPS/GalN-induced acute liver injury
      via activation of the Nrf2 antioxidant pathway and subsequent inhibition of NF
      kappaB-mediated cytokine production. These findings support the potential for
      nobiletin as a therapeutic agent for the treatment of acute liver injury.

PMID- 27878236
TI  - Pyropia yezoensis peptide promotes collagen synthesis by activating the TGF
      beta/Smad signaling pathway in the human dermal fibroblast cell line Hs27.
AB  - Pyropia yezoensis (P. yezoensis) is a marine algae that exhibits antioxidant,
      anti-inflammatory, antitumor and anti-aging activities. In this study, we
      investigated the effects of the P. yezoensis peptide, PYP1-5, on collagen
      synthesis in the human dermal fibroblast cell line Hs27. Skin aging is related to
      reduced collagen production and the activities of multiple enzymes, including
      matrix metalloproteinases (MMPs), which degrade collagen structure in the dermis,
      and tissue inhibitor of tissue inhibitor of metalloproteinases (TIMPs), which
      inhibit the action of MMPs. While collagen synthesis is associated with a number
      of signaling pathways, we examined the increased collagen synthesis via the
      upregulation of the transforming growth factor-beta (TGF-beta)/Smad signaling
      pathway. Using MTS assay, we found that PYP1-5 did not affect cell viability.
      Moreover, we confirmed that PYP1-5 increased type 1 collagen expression using
      enzyme-linked immunosorbent assay (ELISA), western blot analysis and quantitative
      PCR. In addition, we identified changes in various enzymes, as well as the
      mechanisms behind the PYP1-5-induced collagen synthesis. PYP1-5 decreased the MMP
      1 protein and mRNA levels, and increased the TIMP-1 and TIMP-2 protein and mRNA
      levels. In addition, PYP1-5 activated the TGF-beta/Smad signaling pathway, which
      increased TGF-beta1, p-Smad2 and p-Smad3 expression, while inhibiting Smad7, an
      inhibitor of the TGF-beta/Smad pathway. Furthermore, PYP1-5 upregulated
      transcription factor specificity protein 1 (Sp1) expression, which is reportedly
      involved in type 1 collagen expression. These findings indicate that PYP1-5
      activates the TGF-beta/Smad signaling pathway, which subsequently induces
      collagen synthesis in Hs27 cells.

PMID- 27878237
TI  - Inhibition of the growth of human melanoma cells by methionine enkephalin.
AB  - Melanoma is an aggressive cancer, the incidence of which is increasing worldwide.
      Limited therapies are currently available, particularly following metastasis. The
      aim of the present study was to investigate the inhibiting effect of methionine
      enkephalin (MENK) on human melanoma via opioid receptors. The results of the
      present study revealed that MENK markedly regulates the proliferation of A375
      cells, causing cell cycle arrest in G0/G1 phase and a decrease in the percentage
      of cells in S and G2/M phases. Reverse transcription-quantitative polymerase
      chain reaction demonstrated that MENK treatment increased opioid receptor
      expression in A375 cells. Furthermore, the expression level of survivin, an
      inhibitory apoptotic protein, was 1.1% of the level in the control group in the
      MENK group following 48 h of treatment. In conclusion, the results of the present
      study revealed, to the best of our knowledge for the first time, that MENK may
      inhibit growth and induce apoptosis of A375 cells, and describes a potential
      mechanism underlying these effects. Therefore, MENK should be investigated as a
      primary therapy for human melanoma cancer and as an adjuvant to other
      chemotherapies. Further studies are required to develop an optimal strategy for
      the use of MENK for the treatment of human cancers.

PMID- 27878239
TI  - AICAR induces mitochondrial apoptosis in human osteosarcoma cells through an AMPK
      dependent pathway.
AB  - The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide
      ribonucleotide (AICAR) modulates cellular energy metabolism, and promotes
      mitochondrial proliferation and apoptosis. Previous studies have shown that AICAR
      has anticancer effects in various cancers, however the roles of AMPK and/or the
      effects of AICAR on osteosarcoma have not been reported. In the present study, we
      evaluated the effects of AICAR on tumor growth and mitochondrial apoptosis in
      human osteosarcoma both in vitro and in vivo. For in vitro experiments, two human
      osteosarcoma cell lines, MG63 and KHOS, were treated with AICAR, and the effects
      of AICAR on cell growth and mitochondrial apoptosis were assessed by WST assays,
      TUNEL staining, and immunoblot analyses. In vivo, human osteosarcoma-bearing mice
      were treated with AICAR, and the mitochondrial proliferation and apoptotic
      activity in treated tumors were assessed. In vitro experiments revealed that
      AICAR activated AMPK, inhibited cell growth, and induced mitochondrial apoptosis
      in both osteosarcoma cell lines. In vivo, AICAR significantly reduced
      osteosarcoma growth without apparent body weight loss and AICAR increased both
      mitochondrial proliferation and apoptotic activity in treated tumor tissues.
      AICAR showed anticancer effects in osteosarcoma cells through an AMPK-dependent
      peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC
      1alpha)/mitochondrial transcription factor A (TFAM)/mitochondrial pathway. The
      findings in this study strongly suggest that AICAR could be considered as a
      potent therapeutic agent for the treatment of human osteosarcoma.

PMID- 27878240
TI  - SirT1 activator represses the transcription of TNF-alpha in THP-1 cells of a
      sepsis model via deacetylation of H4K16.
AB  - Sepsis is a systemic inflammatory response resulting from the excessive
      production of pro-inflammatory cytokines, including tumor necrosis factor (TNF)
      alpha. Sirtuin 1 (SirT1) actively deacetylates histone proteins, and facilitates
      chromatin compaction and gene silencing. In the present study, a cell model of
      sepsis, comprising lipopolysaccharide (LPS)-tolerant THP-1 cells, was used to
      investigate whether the SirT1 activator, resveratrol, repressed the transcription
      of TNF-alpha. Chromatin immunoprecipitation and real-time PCR were used to
      determine the transcription of the TNF-alpha promoter. The result revealed that
      the binding of SirT1 to the TNF-alpha promoter was decreased by LPS stimulation
      in normal cells. However, in LPS-tolerant cells, nuclear protein levels of SirT1
      remained elevated, and LPS stimulation had no significant effect on the binding
      of SirT1 to the TNF-alpha promoter. However, the activity of SirT1 was increased
      and binding of ace-H4K16 to the TNF-alpha promoter was decreased with resveratrol
      treatment in the tolerant cells. It was concluded that resveratrol stimulated
      sirtuin activity in LPS-tolerant THP-1 cells, and repressed TNF-alpha
      transcription through the deacetylation of H4K16, without affecting the
      methylation of H3K9. Resveratrol offers potential as an infective candidate to
      alleviate inflammation in patients with sepsis.

PMID- 27878241
TI  - Hsa-miR-371-5p inhibits human mesangial cell proliferation and promotes apoptosis
      in lupus nephritis by directly targeting hypoxia-inducible factor 1alpha.
AB  - MicroRNAs (miRNAs/miR) have emerged as a novel class of gene expression
      modulators in kidney disease. Lupus nephritis (LN) is the predominant cause of
      morbidity and mortality in patients with systemic lupus erythematosus (SLE). Hsa
      miR-371-5p has previously been reported to be dysregulated in LN using a miRNA
      microarray analysis. The present study aimed to determine the function and
      molecular mechanisms of hsa-miR-371-5p in human mesangial cells of LN.
      Quantitative polymerase chain reaction (qPCR) was used to detect hsa-miR-371-5p
      expression in LN tissues. Furthermore, the MTT assay and flow cytometric analyses
      were performed to analyze the effects of hsa-miR-371-5p on mesangial cell
      proliferation and apoptosis. Bioinformatics analysis, luciferase reporter assay,
      qPCR and western blotting were also conducted to predict and confirm the target
      gene of hsa-miR-371-5p in mesangial cells. The results demonstrated that hsa-miR
      371-5p expression was markedly downregulated in LN renal tissues compared with in
      normal kidney tissues. Restoration of hsa-miR-371-5p expression using synthetic
      hsa-miR-371-5p mimics was able to significantly inhibit mesangial cell
      proliferation and induce apoptosis. In addition, mechanistic exploration
      demonstrated that hypoxia-inducible factor 1alpha (HIF-1alpha) was a direct
      target gene of hsa-miR-371-5p in mesangial cells. In conclusion, these results
      suggested that hsa-miR-371-5p is downregulated in LN, and overexpression of hsa
      miR-371-5p may inhibit mesangial cell proliferation and promote apoptosis by
      directly targeting HIF-1alpha.

PMID- 27878242
TI  - ESC-3 induces apoptosis of human ovarian carcinomas through Wnt/beta-catenin and
      Notch signaling in vitro and in vivo.
AB  - Apoptosis, programmed cell death under physiological or pathological conditions,
      plays a critical role in the tissue homeostasis of eukaryotes. It is desirable to
      prevent the occurrence and metastasis of cancer through inducing apoptosis. Our
      previous study demonstrated that apoptosis could be induced by extract from
      crocodile in human cholangiocarcinoma. ESC-3, a novel cytotoxic compound isolated
      from the extract induced apoptosis in Mz-ChA-1 cells via the mitochondria
      dependent pathway in a dose-dependent manner. In this study, ESC-3 significantly
      inhibited the proliferation of A2780 cells and arrested the cells at G2/M phase.
      After exposure to ESC-3, A2780 cells displayed typical morphological changes and
      the ability of colony-forming was remarkably inhibited. ESC-3 could significantly
      upregulate the expression of Bax proteins while Bcl-2 protein remained unchanged,
      resulting in the elevation of Bax/Bcl-2 ratio, which usually could induce
      apoptosis. The critical protein of Wnt signaling (beta-catenin) was significantly
      downregulated, whereas Hes1, the downstream protein of Notch signaling, was
      remarkably attenuated through upregulating the expression of P53. In addition,
      xenograft models demonstrated that ESC-3 effectively suppressed the growth of
      OvCa tumors (T/C=42%). Western blot analysis of PCNA and VEGF confirmed that ESC
      3 could inhibit the growth and metastasis of OvCa tumors. In conclusion,
      apoptosis could be induced by ESC-3 through Wnt/beta-catenin and Notch signaling
      in vitro and in vivo, and might have therapeutic potential for the treatment of
      human OvCa.

PMID- 27878244
TI  - MicroRNA-93 is overexpressed and induces apoptosis in glaucoma trabecular
      meshwork cells.
AB  - Glaucoma is an optic neuropathy and a major cause of blindness globally.
      Trabecular meshwork cells are important in maintaining aqueous humor flow, the
      dysfunction of which tends to induce glaucoma. As important regulators of gene
      expression, microRNAs may be crucial in regulating trabecular meshwork cells. The
      present study aimed to reveal the effect of microRNA-93 (miR-93) on glaucoma
      trabecular meshwork (GTM) cell apoptosis. The expression levels of miR-93 were
      compared between human trabecular meshwork (HTM) cells and GTM cells. The
      expression of miR-93 was inhibited and increased by transfecting the cells with a
      lentivirus containing its specific inhibitor sponge and expression vector to
      investigate changes in GTM cell viability and apoptosis. Alterations in the
      protein expression of nuclear factor erythroid 2-like 2 (NFE2L2) were also
      examined to elucidate the possible mechanism underlying the effects of miR-93.
      The results showed a marked promotion in the expression of miR-93 in the GTM
      cells, compared with the HTM cells (P<0.01). GTM cell viability was increased and
      its apoptosis was inhibited by transfection with the miR-93 sponge (P<0.01 and
      P<0.001, respectively), whereas the overexpression of miR-93 abrogated these
      effects (P<0.05 and P<0.0001, respectively). The expression of NFE2L2, a possible
      target of miR-93, was promoted by transfection with the miR-93 sponge (P<0.01)
      and was inhibited in the cells overexpressing miR-93 (P<0.01). Therefore, miR-93
      was capable of inhibiting viability and inducing apoptosis of the GTM cells,
      which was achieved via the suppression of NFE2L2. These results elucidated the
      pro-apoptotic effects of miR-93 in GTM cells and its possible functional
      mechanism, providing potential therapeutic targets for the treatment of glaucoma.

PMID- 27878243
TI  - Different functions of AKT1 and AKT2 in molecular pathways, cell migration and
      metabolism in colon cancer cells.
AB  - AKT is a central protein in many cellular pathways such as cell survival,
      proliferation, glucose uptake, metabolism, angiogenesis, as well as radiation and
      drug response. The three isoforms of AKT (AKT1, AKT2 and AKT3) are proposed to
      have different physiological functions, properties and expression patterns in a
      cell type-dependent manner. As of yet, not much is known about the influence of
      the different AKT isoforms in the genome and their effects in the metabolism of
      colorectal cancer cells. In the present study, DLD-1 isogenic AKT1, AKT2 and
      AKT1/2 knockout colon cancer cell lines were used as a model system in
      conjunction with the parental cell line in order to further elucidate the
      differences between the AKT isoforms and how they are involved in various
      cellular pathways. This was done using genome wide expression analyses, metabolic
      profiling and cell migration assays. In conclusion, downregulation of genes in
      the cell adhesion, extracellular matrix and Notch-pathways and upregulation of
      apoptosis and metastasis inhibitory genes in the p53-pathway, confirm that the
      knockout of both AKT1 and AKT2 will attenuate metastasis and tumor cell growth.
      This was verified with a reduction in migration rate in the AKT1 KO and AKT2 KO
      and most explicitly in the AKT1/2 KO. Furthermore, the knockout of AKT1, AKT2 or
      both, resulted in a reduction in lactate and alanine, suggesting that the
      metabolism of carbohydrates and glutathione was impaired. This was further
      verified in gene expression analyses, showing downregulation of genes involved in
      glucose metabolism. Additionally, both AKT1 KO and AKT2 KO demonstrated an
      impaired fatty acid metabolism. However, genes were upregulated in the Wnt and
      cell proliferation pathways, which could oppose this effect. AKT inhibition
      should therefore be combined with other effectors to attain the best effect.

PMID- 27878245
TI  - Baicalin attenuates DDP (cisplatin) resistance in lung cancer by downregulating
      MARK2 and p-Akt.
AB  - DDP (cisplatin) resistance in lung cancer has been widely reported. Baicalin is a
      flavone glycoside found in genus Scutellaria. However, the effects of baicalin on
      DDP resistance in lung cancer are unclear. The aim of present study was to
      investigate effects of combination of baicalin and DDP on proliferation and
      invasion of human lung cancer cells, and explore possible mechanisms. MTT assay
      was utilized to evaluate effects of baicalin and DDP on the proliferation of A549
      and A549/DPP (DPP-resistant) human lung cancer cells. The probability sum method
      was used to determine effects of the drug combination. Transwell invasion assay
      was utilized to detect tumor cell invasion. The mRNA expression of MARK2 in A549
      and A549/DPP cells was detected by qPCR. Protein expression of MARK2, p-Akt and
      Akt was detected by western blot analysis. Baicalin and DPP when used alone
      inhibited the proliferation of A549 and A549/DDP cells in a dose-dependent manner
      at 24 and 48 h. For A549 cells, baicalin (8 ug/ml) antagonized DDP (1, 2, 4 and 8
      ug/ml) at 24 h. For A549/DDP cells, baicalin and DDP were additive when the
      concentration of DDP was 4 ug/ml at 24 h. Effects of baicalin and DDP on
      proliferation inhibition were additive and synergistic when concentrations of DDP
      were 8 and 4 ug/ml, respectively, at 48 h for both A549 and A549/DDP cells. When
      baicalin (8 ug/ml) and DDP (4 ug/ml) were combined, the inhibitory rate of tumor
      cell invasion increased markedly compared to DPP or baicalin alone groups in both
      A549 and A549/DDP cells. A549/DDP cells had significantly higher MARK2 mRNA
      levels and protein expression of MARK2 and p-Akt. Baicalin decreased MARK2 mRNA
      and protein expression of MARK2 and p-Akt in A549/DDP cells dose-dependently. In
      conclusion, baicalin and DDP were synergistic at inhibiting proliferation and
      invasion of human lung cancer cells at appropriate dosages and incubation time in
      the presence or absence of DDP resistance. The attenuation of DDP resistance was
      associated with downregulation of MARK2 and p-Akt.

PMID- 27878247
TI  - Oridonin inhibition and miR-200b-3p/ZEB1 axis in human pancreatic cancer.
AB  - The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial
      to-mesenchymal transition (EMT) was investigated for the molecular mechanism or
      signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells
      were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained
      by the CCK-8 array. The expression of miR-200b-3p was verified by using real-time
      PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with
      oridonin or transfected by miR-200b-3p, those cells were used for western blot
      assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay
      in nude mice and immunohistochemical assay to verify the effects of oridonin or
      miR-200b-3p on pancreatic cancer. We found that oridonin inhibited the
      proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner. miR-200b-3p
      was downregulated by oridonin in BxPC-3 and PANC-1 cells. ZEB1 was a target gene
      for miR-200b-3p. Oridonin or overexpression of miR-200b-3p can inhibit the cell
      migration in BxPC-3 and PANC-1 cells. miR-200b-3p can inhibit the EMT and
      oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not
      increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1
      and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the
      cytoskeleton was altered by oridonin in PANC-1 cells compared with the control.
      In summary, the results demonstrate that miR-200b-3p was able to inhibit the EMT
      of human pancreatic cancer in vivo and in vitro by targeted ZEB1. In vitro,
      oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but
      not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type II
      EMT, tumor microenvironment or altering the cytoskeleton. In vivo, oridonin
      inhibited the cancer migration in the nude mouse model though inhibiting EMT.

PMID- 27878246
TI  - Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated
      anti-inflammatory and antioxidant effects.
AB  - Reseda odorata L. has long been used in traditional Asian medicine for the
      treatment of diseases associated with oxidative injury and acute inflammation,
      such as endotoxemia, acute lung injury, acute myocardial infarction and
      hepatitis. Luteolin, the main component of Reseda odorata L., which is also
      widely found in many natural herbs and vege-tables, has been shown to induce heme
      oxygenase-1 (HO-1) expression to exert anti-inflammatory and antioxidant effects.
      In this study, we aimed to examine the effects of luteolin on mice with severe
      acute pancreatitis (SAP), and to explore the underlying mechanisms. Cerulein and
      lipopolysaccharide were used to induce SAP in male Institute of Cancer Research
      (ICR) mice in the SAP group. The SAP group was divided into 4 subgroups, as
      follows: the vehicle, luteolin, zinc protoporphyrin (ZnPP) only, and luteolin
      (Lut) + ZnPP (luteolin plus zinc protoporphyrin treatment) groups. The wet/dry
      weight ratios, hematoxylin and eosin staining and pathological scores of
      pancreatic tissues were assessed and compared to those of the control mice.
      Amylase, lipase, nuclear factor-kappaB (NF-kappaB) and myeloperoxidase
      activities, and malondialdehyde, tumor necrosis factor alpha (TNFalpha),
      interleukin (IL)-6, IL-10 and HO-1 levels, as well as the expression of HO-1 were
      determined in serum and/or pancreatic tissue samples. SAP was successfully
      induced in male mice compared to normal control mice. The wet/dry weight ratios,
      pathological scores, and amylase and lipase activity, as well as the levels of
      TNFalpha and IL-6 were significantly reduced in the pancreatic tissues of the
      mice in the Lut group compared with those of the mice in the vehicle group. The
      Lut group exhibited a significant increase in HO-1 expression in the pancreas and
      enhanced serum HO-1 and IL-10 levels compared with the vehicle group. The
      suppression of HO-1 activity in the ZnPP group significantly abolished the
      protective effects of luteolin. NF-kappaB expression in the pancreatic tissues
      from the mice in the Lut + ZnPP group was significantly increased following the
      suppression of HO-1 activity. On the whole, our findings demonstrate that
      luteolin protects mice from SAP by inducing HO-1-mediated anti-inflammatory and
      antioxidant activities, in association with the suppression of the activation of
      the NF-kappaB pathway.

PMID- 27878249
TI  - ETS-1: A potential target of glycolysis for metabolic therapy by regulating
      glucose metabolism in pancreatic cancer.
AB  - Pancreatic cancer is one of the most lethal malignancies of all types of cancer
      due to lack of early symptoms and its resistance to conventional therapy. In our
      previous study, we have shown that v-ets erythroblastosis virus E26 oncogene
      homolog-1 (ETS-1) promote cell migration and invasion in pancreatic cancer cells.
      However, the function of ETS-1 in regulation of glycolysis and autophagy during
      progression of pancreatic cancer has not been defined yet. In this study, we
      sought to identify the potential role for silencing ETS-1 in reducing the
      expression of glucose transporter-1 (GLUT-1) to disturb glycolysis through
      alteration of 'Warburg effect', by which could result in AMP-activated protein
      kinase (AMPK) activation, autophagy induction and reduction of cell viability.
      MTT assay was applied to assess the cell viability in ETS-1 silencing cells and
      control groups. Glucose absorption rate, lactate production rate and cellular ATP
      level were measured by standard colorimetric assay kits. The levels of mRNAs of
      ETS-1, GLUT-1, autophagy-related gene 5 (ATG5) and ATG7 were analyzed by qRT-PCR.
      The expression of ETS-1, GLUT-1, ATG5, ATG7, p-AMPK, and LC3II proteins were
      evaluated by western blot analysis. GraphPad Prism 5.0 was used for all
      statistical analysis. We found that cell viability was obviously attenuated after
      silencing ETS-1. Besides, our results also showed that the expression of GLUT-1
      significantly declined in ETS-1 silencing cell lines which resulted in a lower
      glucose utilization and lactate production. Furthermore, the inhibition of
      glycolysis, which depends on glucose utilization and lactate production, reduced
      the generation of energy in the form of ATP. Moreover, the reduction of cellular
      ATP was associated with stimulation of AMP-activated protein kinase (AMPK) and
      induction of autophagy. Our results indicated that ETS-1 induced autophagy after
      inhibition of glycolysis, and thus led to comparative decrease of cell viability.
      These results implied that ETS-1 could be a potential target for tumor metabolic
      therapy.

PMID- 27878250
TI  - SN38 increases IL-8 expression through the MAPK pathways in HCT8 cells.
AB  - The overexpression of interleukin-8 (IL-8) is closely associated with poor tumor
      differentiation, metastasis and tumor progression. This study aimed to examine
      the effects and mechanisms of action of SN38 (a metabolite of the camptothecin
      derivative, CPT-11) on IL-8 expression in HCT8 cells, using ELISA, CCK-8 and
      western blot analysis. Among jatrorrhizine, evodiamine, 5-fluorouracil and SN38,
      SN38 was found to inhibit the proliferation of HCT8 cells in a dose-dependent
      manner, but to increase IL-8 secretion from HCT8 cells. Of the other agents,
      evodiamine was found to inhibit both IL-8 secretion and cell proliferation, and
      jatrorrhizine was found to increase IL-8 secretion without any obvious inhibitory
      effect on cell proliferation. Further experiments revealed that the increased
      activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal
      regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) by SN38 contributed
      to the decreased cell proliferation and to the overexpression of IL-8 induced by
      SN38. Our results suggested that the MAPK pathways are activated by SN38,
      resulting in the upregulation of IL-8 expression and in the inhibition of cell
      proliferation in an IL-8-independent manner. Thus, the potential benefit of the
      use of a combination of camptothecin-11 with other chemical drugs with inhibitory
      effects on IL-8 expression, should be paid more attention in treating colon
      cancer.

PMID- 27878251
TI  - Glyceraldehyde-3-phosphate dehydrogenase promotes cancer growth and metastasis
      through upregulation of SNAIL expression.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in
      multiple cellular functions including metabolism and gene transcription. Our
      previous study showed that GAPDH expression was elevated in colon cancer and
      further upregulated in liver metastatic tissues, suggesting a possilbe role of
      GAPDH in promoting cancer metastasis. The present study was designed to
      investigate the underlying mechanism, using multiple experimental approaches
      including genetic silencing of GAPDH expression by short hairpin RNA (shRNA) and
      biochemcial/molecular analyses of the key events involved in glycolytic
      metabolism and epithelial-mesenchymal transition (EMT). We showed that silencing
      of GAPDH expression resulted in a significant reduction of glycolysis in colon
      cancer cell lines, accompanied by a decrease in cell proliferation and an
      apparent change in cell morphology associated with alterations in actin
      expression and phalloidine staining patterns. Furthermore, GAPDH suppression also
      caused a downregulation of gene expression involved in cancer stem-like cells and
      EMT. CHIP assay and co-immunoprecipitation revealed that GAPDH physically
      interacted with the transcriptional factor Sp1 and enhance the expression of
      SNAIL, a major regulator of EMT. Suppression of GAPDH expression resulted in a
      signficant decrease in SNAIL expression, leading to inhibition of EMT and
      attenuation of colon cancer cell migration in vitro and reduced metastasis in
      vivo. Overall, the present study suggests that GAPDH plays an important role in
      cancer metastasis by affecting EMT through regulation of Sp1-mediated SNAIL
      expression.

PMID- 27878248
TI  - Immunomodulatory effects of OX40Ig gene-modified adipose tissue-derived
      mesenchymal stem cells on rat kidney transplantation.
AB  - Recent studies have suggested that adipose tissue-derived mesenchymal stem cell
      (ADSC) therapy and OX40 costimulation blockade are two immunomodulatory
      strategies used to suppress the immune response to alloantigens. However,
      relatively little has been reported regarding the immunomodulatory potential of
      the abilityof these two strategies to synergize. Thus, in the present study, we
      aimed to investigate OX40-Ig fusion protein (OX40Ig) expression in ADSCs and to
      validate their more potent immunosuppressive activity in preventing renal
      allograft rejection. For this purpose, ADSCs from Lewis rats were transfected
      with the recombinant plasmid, pcDNA3.1(-)OX40Ig, by nucleofection. The ADSCs
      transduced with the plasmid (termed ADSCsOX40Ig) or untransduced ADSCs (termed
      ADSCsnative) were added to allostimulated mixed lymphocyte reaction (MLR) in
      vitro. In vivo, ADSCsOX40Ig, ADSCsnative, or PBS were administered to an
      allogeneic renal transplantation model, and the therapeutic effects, as well as
      the underlying mechanisms were examined. The results revealed that both the
      ADSCsnative and ADSCsOX40Ig significantly suppressed T cell proliferation and
      increased the percentage of CD4+CD25+ regulatory T cells in allogeneic MLR
      assays, with the ADSCsOX40Ig being more effective. Furthermore, the results from
      our in vivo experiments revealed that compared with the ADSCsnative or PBS group,
      the administration of autologous ADSCsOX40Ig markedly prolonged the mean survival
      time of renal grafts, reduced allograft rejection, and significantly
      downregulated the mRNA expression of intragraft interferon-gamma (IFN-gamma) ,
      and upregulated the mRNA expression of interleukin (IL)-10, transforming growth
      factor-beta (TGF-beta) and forkhead box protein 3 (Foxp3). The findings of our
      study indicate that the use of ADSCsOX40Ig is a promising strategy for preventing
      renal allograft rejection. This strategy provides the synergistic benefits of
      ADSC immune modulation and OX40-OX40L pathway blockade, and may therefore have
      therapeutic potential in clinical renal transplantation.

PMID- 27878252
TI  - Temozolomide inhibits cellular growth and motility via targeting ERK signaling in
      glioma C6 cells.
AB  - Temozolomide (TMZ) is an alkylating agent used for the treatment of aggressive
      forms of brain tumor based on its antitumor actions. However, the exact effect on
      cancer and the underlying anticancer molecular mechanism of TMZ remain to be
      elucidated. In the present study, the effects of TMZ on the growth and motility
      of glioma C6 cells were investigated. MTT and Transwell assays were used to
      detect cellular growth and motility. The results showed that TMZ inhibited the
      proliferation, migration and invasion of the glioma C6 cells in vitro, western
      blot analysis determined that the phosphorylation of extracellular signal
      regulated protein kinase (ERK)1/2 was decreased in the TMZ-treated cells,
      compared with the untreated control cells. The ERK1/2 specific inhibitor, U0126,
      augmented the inhibitory effects of TMZ on the proliferation, migration and
      invasion of the glioma C6 cells, and the mitogen-activated protein kinase
      kinase/ERK pathway activator, curcumin, attenuated the inhibitory effects of TMZ
      on the proliferation and motility of the glioma C6 cells. Additionally, the
      western blotting in the present study demonstrated that TMZ and U0126 decreased
      the expression of vascular endothelial growth factor-C (VEGF-C), and the
      expression level was restored by curcumin, suggesting that VEGF-C may be the
      downstream effector of ERK1/2. Furthermore, the overexpression of VEGF-C enhanced
      the growth, migration and invasion of the TMZ-treated cells. These results
      suggested that TMZ suppressed glioma C6 cell development, at least in part, and
      downregulated the expression of VEGF-C by inhibiting the ERK signaling pathway.
      The results of the present study provides the foundation for a combinational
      therapeutic strategy to improve the efficacy of TMZ.

PMID- 27878253
TI  - Development of a therapeutic model of precancerous liver using crocin-coated
      magnetite nanoparticles.
AB  - Despite considerable advances in understanding hepatocellular carcinoma, it is
      one of the common and deadliest cancers worldwide. Hence, increasing efforts are
      needed for early diagnosis and effective treatments. Saffron has been recently
      found to inhibit growth of liver cancer in rats. The aim of this study was to
      develop an effective method for treatment of liver cancer using magnetite
      nanoparticles (MNPs) coated with crocin, the main active component of saffron.
      MNPs were prepared and initially coated with dextran and a cross-linker to
      enhance conjugation of crocin using a modified coprecipitation method. Cultured
      HepG2 cells and diethylnitrosamine-injected mice were treated with corcin-coated
      MNPs and analyzed using cell proliferation assay and immunohistochemical
      analysis, respectively. Treatment of HepG2 cells with crocin-coated MNPs led to a
      significant inhibition of their growth as compared to control or those treated
      with free crocin or uncoated MNPs. Histological examinations of the livers of
      diethylnitrosamine-injected mice revealed several precancerous changes: multiple
      proliferative hepatic foci, hyper- or dysplastic transformations of bile
      ducts/ductules, and nuclear atypia associated with polyploidy, karyomegaly, and
      vacuolation. Immunohistochemistry using antibodies specific for cell
      proliferation (Ki-67) and apoptosis (M30-CytoDEATH and Bcl-2) revealed their
      upregulation during development of precancerous lesions. Using antibodies
      specific for inflammation (cyclooxygenase-2), oxidative stress (glutathione) and
      angiogenesis (vascular endothelial growth factor) indicated the involvement of
      multiple signaling pathways in the development of precancerous lesions. Treatment
      with crocin-coated MNPs was associated with regression of precancerous lesions,
      significant upregulation of apoptotic cells and downregulation of Bcl-2 labeling
      and markers of cell proliferation, inflammation, oxidative stress and
      angiogenesis. In conclusion, crocin-coated MNPs are more effective than free
      corcin for treatment of liver precancerous lesions in mice. These findings will
      help to develop new modalities for early detection and treatment of liver
      precancerous lesions.

PMID- 27878254
TI  - Restoration of the tumor-suppressor function to mutant p53 by Ganoderma lucidum
      polysaccharides in colorectal cancer cells.
AB  - Ganoderma lucidum polysaccharides (GLPs), isolated from spores, mycelia and
      fruiting bodies of Ganoderma lucidum, have been suggested to possess anticancer
      activities in a large number of basic studies. A recent survey revealed that GLP
      induced inhibition of cancer cell growth was dependent on the existence of
      functional p53. However, the actual role of p53-mediated tumor-suppressing
      pathways in facilitating the anticancer effect of GLPs is still unclear. In the
      present study, we investigated the interaction between GLPs and mutant p53 that
      exists in more than half of the known types of cancers. Our results showed that
      GLPs reactivated mutant p53 in colorectal cancer HT29 (p53R273H) and SW480
      (p53R273H&P309S) cells while applied alone or together with 5-fluorouracil (5
      FU). This reactivation further induced cell growth inhibition and apoptosis. In
      addition, western blot assay and in vitro cell-free apoptosis assay suggested
      that the activation of mutant p53 was effective in both a transcriptional
      dependent and -independent pathway. Altogether, our data demonstrated for the
      first time that GLPs show prominent anticancer activities by reactivating several
      types of mutant p53. Therefore, targeting mutant p53 by GLPs alongside other
      chemotherapeutics may be considered as a novel treatment strategy for cancer.

PMID- 27878256
TI  - Melatonin attenuates TGFbeta1-induced epithelial-mesenchymal transition in lung
      alveolar epithelial cells.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease.
      However, the pathogenesis remains to be fully elucidated. Melatonin is secreted
      by the pineal gland, it has a strong antioxidant effect, and exerts an anti
      fibrosis effect. Whether melatonin attenuates pulm -onary fibrosis by inhibiting
      epithelial-mesenchymal transition (EMT) requires further research. The present
      study aimed to investigate whether melatonin prevents transforming growth factor
      beta1 (TGF-beta1)-induced EMT and underlying signaling pathways using reverse
      transcription-quantitative polymerase chain reaction, western blot analysis and
      immunofluorescence. The results demonstrated that melatonin inhibits EMT in A549
      cells, and the Wnt/beta-catenin and Smad2/3 signaling pathways are involved in
      the EMT of the A549 cell line as they were suppressed by melatonin. The present
      study indicates that melatonin inhibited TGFbeta1-induced epithelial-mesenchymal
      transition in the A549 cell line and may potentially be useful in the treatment
      of IPF.

PMID- 27878255
TI  - Roles of mitochondrial transcription factor A and microRNA-590-3p in the
      development of colon cancer.
AB  - Mitochondrial transcription factor A (TFAM) participates in the process of
      mitochondrial DNA replication and transcription. microRNAs (miRNAs) serve an
      important role in the regulation of gene expression. However, the roles of TFAM
      and certain miRNAs and their associations in the development of numerous cancer
      types remain unclear. The current study demonstrated that the expression of TFAM
      was significantly upregulated in colon cancer compared with the normal tissue,
      while the expression of miRNA-590-3p (miR-590-3p) was predicted with a high score
      using miRWalk software, and the luciferase assay demonstrated that TFAM was the
      direct target of miRNA-590-3p. miR-590-3p exhibited high expression levels in
      both colon cancer tissue and the SW480 cell line. Furthermore, downregulated
      expression of miR-590-3p significantly inhibited the growth of SW480 cells, which
      was consistent with results indicating downregulated expression of TFAM in SW480
      cells from a previous study. In summary, the results of the current study
      concluded that miR-590-3p, via direct targeting of TFAM, may serve an important
      role in the tumorigenesis of colon cancer, and may be a promising target for
      colon cancer therapeutics.

PMID- 27878257
TI  - Downregulation of Bmi-1 suppresses epithelial-mesenchymal transition in melanoma.
AB  - Epithelial-mesenchymal transition (EMT) contributes to the invasion and
      metastasis of numerous malignant cancers, including melanoma. A significant
      higher expression of B-lymphoma Moloney murine leukemia virus insertion region-1
      (Bmi-1) has been reported in cell lines from metastatic melanoma compared to cell
      lines from primary melanoma. There are studies that show that knockdown of Bmi-1
      could induce E-cadherin expression in melanoma cells. However, the role of Bmi-1
      in mediating EMT-like changes in melanoma has not yet been fully studied. In the
      present study, knockdown of Bmi-1 by shRNA transduction decreased the invasion
      properties of the cultured human melanoma cells A375 by a Matrigel invasion
      assay, along with alterations in EMT-related markers E-cadherin, alpha-catenin,
      vimentin and N-cadherin. The aforementioned altered expression of EMT markers was
      verified in BALB/c-nude mouse xenografts. Furthermore, to explore the underlying
      regulatory mechanism of EMT, we detected the significant downregulation of p
      Akt/p-NF-kappaB/MMP-2 and the upregulation of PTEN in Bmi-1-silenced A375 cells.
      The present study demonstrated that knockdown of Bmi-1 significantly inhibited
      the aggressive behavior of melanoma by reversing EMT-like changes via the PTEN/p
      Akt/p-NF-kappaB/MMP-2 pathway.

PMID- 27878258
TI  - MicroRNA-362 is downregulated in cervical cancer and inhibits cell proliferation,
      migration and invasion by directly targeting SIX1.
AB  - Cervical cancer is the second most common type of cancer in women accounting for
      12% of all human cancers in the world. Mounting evidence demonstrates that
      microRNAs play important roles in the carcinogenesis and progression of cervical
      cancer. The aim of this study was to investigate the expression, roles and
      molecular mechanism of microRNA-362 (miR-362) in cervical cancer. According to
      the results, we found that expression level of miR-362 was significantly reduced
      in cervical cancer tissues and cell lines. Low miR-362 expression was correlated
      with FIGO stage, lymph node metastasis and vascular invasion in cervical cancer.
      Functional assays showed that restoration of miR-362 repressed cell
      proliferation, migration and invasion in cervical cancer. We also provided direct
      evidence that sineoculis homeobox homolog 1 (SIX1) was a direct target of miR-362
      in cervical cancer, which was confirmed by bioinformatics analysis, luciferase
      reporter assay, qRT-PCR and western blot analysis. SIX1 was upregulated in
      cervical cancer and inversely correlated with miR-362 expression in cervical
      cancer. In addition, SIX1 knockdown could simulate the roles of miR-362
      overexpression on cell proliferation, migration and invasion of cervical cancer.
      Moreover, rescue experiments indicated that restoration of SIX1 was sufficient to
      abolish proliferation, migration and invasion induced by miR-362 overexpression
      in cervical cancer cells. The newly identified miR-362/SIX1 pathway provides
      insight into cervical cancer progression, and may represent a novel therapeutic
      target.

PMID- 27878259
TI  - Stanniocalcin 2 improved osteoblast differentiation via phosphorylation of ERK.
AB  - Mammalian stanniocalcin 2 (STC2) is a glycoprotein hormone with multiple
      functions. The present study determined the importance of STC2 in osteoblast
      differentiation. It was revealed that the expression of STC2 was increased during
      the differentiation of MC3T3-E1 cells to osteoblasts and that knockdown of STC2
      reduced osteoblast differentiation and mineralization, whereas STC2
      overexpression increased differentiation and mineralization. Knockdown of STC2
      downregulated the expression of osteoblast-associated genes, including runt
      related transcription factor 2, collagen type I alpha 1 chain, osterix and
      osteocalcin. Overexpression of STC2 upregulated the expression of these
      osteoblastic genes. In addition, overexpression of STC2 enhanced the
      phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whereas
      inhibition of ERK phosphorylation reduced osteoblast differentiation of MC3T3-E1
      cells overexpressing STC2. These findings indicated that STC2 may promote
      osteoblast differentiation and mineralization by regulating ERK activation.

PMID- 27878260
TI  - miR-3619-5p inhibits prostate cancer cell growth by activating CDKN1A expression.
AB  - Recent studies have shown that miRNAs have potent abilities to activate gene
      expression by targeting promoter elements, a phenomenon known as RNA activation
      (RNAa). In the present study, we identified a new endogenous miR-3619-5p which
      was decreased in prostate cancer tissues and cells compared to corresponding
      normal controls. Moreover, overexpression of miR-3619-5p readily induced CDKN1A
      gene expression by directly targeting the putative site in the promoter. Besides,
      miR-3619-5p possessed considerable capacity to inhibit prostate cancer DU145 and
      PC3 cell growth, and downregulate several CDKN1A downstream genes, such as cyclin
      D1, CDK4 and CDK6. Notably, this antitumor function of miR-3619-5p was mainly
      achieved by stimulating CDKN1A expression.

PMID- 27878261
TI  - Bacterial ghosts as adjuvants in syngeneic tumour cell lysate-based anticancer
      vaccination in a murine lung carcinoma model.
AB  - Instead of relying on external anticancer factors for treatment, immunotherapy
      utilizes the host's own immune system and directs it against given tumour
      antigens. This study demonstrated that it is possible to overcome the documented
      immunosuppressive properties of tumour cell lysate by supplementing it with
      appropriate adjuvant. Lewis lung carcinoma (LLC)-challenged C57BL/6 mice were
      treated with LLC cryo-lysate mixed with either bacterial ghosts (BGs) generated
      from E. coli Nissle 1917 or B. subtilis 70 kDa protein as adjuvants. Median and
      overall survival, the size of metastatic foci in lung tissue and levels of
      circulating CD8a+ T cells were evaluated and compared to the untreated control
      mice or mice treated with LLC lysate alone. After primary tumour removal, a
      course of three subcutaneous vaccinations with LLC lysate supplemented with BGs
      led to a significant increase in overall survival (80% after 84 days of follow-up
      vs. 40% in untreated control mice), a significant increase in circulating CD8a+ T
      cells (16.57 vs. 12.6% in untreated control mice) and a significant decrease in
      metastasis foci area and incidence. LLC lysate supplemented with B. subtilis
      protein also improved the inspected parameters in the treated mice, when compared
      against the untreated control mice, but not to a significant degree. Therefore,
      whole cell lysate supplemented with BGs emerges as an immunostimulatory construct
      with potential clinical applications in cancer treatment.

PMID- 27878262
TI  - Identification of suitable reference genes for BDV-infected primary rat
      hippocampal neurons.
AB  - Borna disease virus (BDV) is a neurotropic RNA virus that infects the limbic
      system of mammals and results in behavioral disorders. The hippocampus is a core
      region in the limbic system, which contributes to memory and learning and is
      important in the regulation of emotion. However, no validated microRNA
      housekeeping genes have yet been identified in BDV-infected rat primary
      hippocampal neurons. Proper normalization is key in accurate miRNA expression
      analysis. The present study used reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) to evaluate the expression stability of 10 commonly used
      reference genes [miR-92a, 5S, U6, miR-103, miR-101a, miR-let-7a, miR-16, E2 small
      nucleolar RNA (snoRNA), U87 and miR-191] in BDV-infected rat hippocampal neurons
      and non-infected controls across 12 days post-infection. The data was analyzed by
      four statistical algorithms: geNorm, NormFinder, BestKeeper, and the comparative
      Delta-Ct method. Subsequently, the most suitable reference genes (miR-101a and
      U87) and the least suitable (snoRNA) were determined by the RankAggreg package.
      miR-155 was selected as a standard by which to evaluate the most and least
      suitable reference genes. When normalized to the most stable reference gene there
      were significant differences between the two groups. However, when the data were
      normalized to the less stably expressed gene, the results were not significant.
      miR-101a was recommended as a suitable reference gene for BDV-infected rat
      primary hippocampal neurons.

PMID- 27878263
TI  - Capn4 promotes epithelial-mesenchymal transition in human melanoma cells through
      activation of the Wnt/beta-catenin pathway.
AB  - Melanoma, as one of the most highly metastatic types of cancer, is resistant to
      current treatment methods, including popular targeted molecular therapy.
      Consequently, it is essential to develop a deeper understanding of the mechanisms
      involved in melanoma progression so that alternative treatments may be
      identified. To date, accumulating evidence supports the use of calpains,
      including calpain small subunit 1 (also known as Capn4 or CAPNS1), which affect
      cancer progression through many pathways, such as epithelial-mesenchymal
      transition (EMT), the Wnt/beta-catenin (beta-catenin) and the nuclear factor
      kappaB (NF-kappaB) signaling pathways. The EMT pathway is well known as one of
      the most important events in tumor metastasis. The present study observed cross
      talk among the EMT, beta-catenin and NF-kappaB pathways. To identify the
      underlying mechanisms of Capn4 activity in melanoma cells, we determined Capn4
      expression by gene chip and immunohistochemistral analyses in melanoma tissues
      and cells in vitro. The extent of apoptosis as determined by TUNEL assay, DAPI
      staining, and cleaved-caspase-3 assay was increased in human melanoma cells in
      which Capn4 expression had been knocked down when compared with untreated cells.
      Transwell assays and xenograft tumorigenicity studies were also performed to
      assess the effects of Capn4 on migration and invasion in vitro and tumor growth
      in vivo, respectively. The levels of beta-catenin, vimentin, E-cadherin and N
      cadherin were altered in human melanoma cells as determined by western blot
      analysis assay. Our study demonstrated that Capn4 is an underlying target for
      melanoma treatment.

PMID- 27878264
TI  - Silencing of ANXA3 expression by RNA interference inhibits the proliferation and
      invasion of breast cancer cells.
AB  - The present study aimed to explore the expression of Annexin A3 (ANXA3) in breast
      cancer cells and the mechanisms involved in the regulatory effects of ANXA3 on
      proliferation, invasion and migration of breast cancer cells. Fluorescence
      quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and
      western blotting were used to measure the expression of ANXA3 mRNA and protein in
      two breast cancer cell lines (MDA-MB-231 and MCF-7). Three ANXA3 silencing shRNA
      plasmids (ANXA3-sh1-3) and one negative control plasmid were constructed, and the
      Lipofectamine transfection method was used for transfecting human breast cancer
      cell line MDA-MB-231. Flow cytometry was used to measure the transfection
      efficiency. The expression of ANXA3 protein was measured by western blotting.
      Cell cycle distribution and apoptosis were assessed by flow cytometry. Migration
      and invasion of the transfected cells were evaluated using wound healing and
      Transwell assays, respectively. The expression levels of ANXA3 mRNA and protein
      were significantly higher in the MDA-MB-231 cells than levels in the MCF-7 cells.
      Western blotting showed that the ANXA3 protein level was significantly lower in
      the MDA-MB-231-Sh cells than that in the MDA-MB-231 and MDA-MB-231-NC cells. In
      addition, the percentage of G0/1 cells and the apoptosis rate were significantly
      higher, while the cell proliferation rate was significantly lower, in the MDA-MB
      231-Sh cells when compared with the MDA-MB-231-NC and MDA-MB-231 cells. The cell
      migration and invasion abilities were also lower in the MDA-MB-231-Sh cells than
      these abilities in the MDA-MB-231-NC and MDA-MB-231 cells. The present study
      investigated the relationships between ANXA3 and proliferation, apoptosis,
      migration and invasion of breast cancer cells to elucidate the mechanisms
      involved in the development, progression, invasion and metastasis of breast
      cancer.

PMID- 27878266
TI  - Cantharidin induces G2/M arrest and triggers apoptosis in renal cell carcinoma.
AB  - The present study aimed to investigate the effects of cantharidin on cell cycle
      distribution, the induction of apoptosis, and Notch1 and Jagged1 expression in
      ACHN and Caki-1 renal cancer cells. Cell viability assay, flow cytometry, cell
      cycle and western blot analyses were performed for ACHN and Caki-1 cells.
      Immunohistochemistry was used to analyze the expression of Notch1 and Jagged1 in
      RCC tissues The results demonstrated that treatment with cantharidin exerted a
      dose- and time-dependent effect on cell viability, apoptosis induction and G2/M
      phase cell cycle arrest. Exposure of ACHN and Caki-1 cells to 20 uM cantharidin
      reduced cell viability to 26 and 32% respectively, after 48 h. In addition,
      treatment with cantharidin enhanced the number of ACHN and Caki-1 cells in G2/M
      phase to 54.62 and 51.88% respectively, as compared with 17.16 and 16.53% in the
      control groups. In the ACHN and Caki-1 cells, treatment with cantharidin induced
      a marked increase in the proportion of apoptotic cells after 48 h. Furthermore,
      cantharidin enhanced the percentage ACHN and Caki-1 apoptotic cells to 57.23 and
      62.34% respectively, as compared with 2.27 and 3.06% in the control groups.
      Detection of Notch1 and Jagged1 expression demonstrated that levels were
      significantly increased in carcinoma tissues. Conversely, cantharidin exhibited
      an inhibitory effect on Notch1 and Jagged1 expression after 48 h. Therefore,
      treatment with cantharidin may exert a promising effect on the inhibition of
      renal cancer, and may be of therapeutic importance for the treatment of renal
      cancer.

PMID- 27878265
TI  - Synergistic effects of overexpression of BMP-2 and TGF-beta3 on osteogenic
      differentiation of bone marrow mesenchymal stem cells.
AB  - Bone morphogenetic protein 2 (BMP-2) and transforming growth factor beta (TGF
      beta) isoforms are important in advancing bone regeneration. The aim of the
      present study was to investigate the positive and reciprocal effect of TGF-beta3,
      one of the three TGF-beta isoforms, on BMP-2 in promoting osteogenic
      differentiation. Exogenous BMP-2 and TGF-beta3 genes were separately, and in
      combination, overexpressed in rabbit bone marrow-derived mesenchymal stem cells
      (rBMSCs). Expression levels of BMP-2 and TGF-beta3 were evaluated using reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blotting assays.
      Furthermore, the osteogenic differentiation capacities of BMSCs were assessed by
      measuring Alizarin Red S staining, an alkaline phosphatase activity assay, and
      quantification of the osteogenic-specific genes, Runt-related transcription
      factor 2 (Runx2) and Osterix (Osx). Using lentiviral-mediated transfection,
      robust co-transfection efficiency of >90% was achieved. RT-PCR and immunoblotting
      results indicated a marked elevated expression of BMP-2 and TGF-beta3 in rBMSCs
      undergoing co-transfection, compared with transfection with BMP-2 or TGF-beta3
      alone, indicating that BMP-2 and TGF-beta3 are synergistically expressed in
      rBMSCs. Furthermore, enhanced osteogenic differentiation was observed in rBMSCs
      co-transfected with BMP-2/TGF-beta3. The present study successfully delivered BMP
      2 together with TGF-beta3 into rBMSCs with high efficiency for the first time.
      Furthermore, TGF-beta3 overexpression was demonstrated to enhance the osteogenic
      efficacy of BMP-2 in rBMSCs, and vice versa. This provides a potential clinical
      therapeutic approach for regenerating the function of osseous tissue, and may
      present a promising strategy for bone defect healing.

PMID- 27878267
TI  - Distribution, pharmacokinetics and primary metabolism model of tramadol in
      zebrafish.
AB  - The current study aimed to develop a rapid, robust and adequately sensitive
      method for simultaneous determination of the concentration of tramadol and its
      active metabolites in zebrafish. The pharmacokinetic and elimination pattern of
      tramadol and its major phase I metabolites following oral or intramuscular
      administration in zebrafish tissues was achieved using electrospray ionization
      quadrupole-time of flight/mass spectrometry (ESI-Q-TOF/MS) and gas
      chromatography/mass spectrometry (GC-MS). Following administration, the
      metabolisms were detected in the brain, eyes, muscle and gill tissues within 1 h.
      Two tramadol metabolites, O- and N-desmethyltramadol, were detected in brain
      tissue, with N-desmethyltramadol detected at a higher level. Following GC-MS
      detection the curve indicated an initial rapid phase, corresponding to the
      detection of the tramadol within 1 min, and reached peak value in the brain at 5
      min. Faster drug clearance was detected in low-dose groups, and concentration had
      dropped around the to initial level (1.11 ug) at 20 min, but was detectable for
      up to 3 h. However, it took 80 min to fall back to the initial value (1.73 ug) in
      the high-dose groups, and tramadol was detectable for up to 4 h. This study
      developed and validated a simple and high throughput analytical procedure to
      determine the distribution and pharmacokinetic profiles of tramadol, and its
      primary metabolites in tissues of zebrafish.

PMID- 27878268
TI  - Crocus sativus L. protects against SDS-induced intestinal damage and extends
      lifespan in Drosophila melanogaster.
AB  - Medicinal plants are important sources of potentially therapeutic biochemical
      drugs. Crocus sativus L. has been used to treat various diseases in China, the
      Republic of Korea and Japan. The present study investigated the protective effect
      of C. sativus L. extract in Drosophila melanogaster intestinal immunity. Wild
      type flies were fed standard cornmeal-yeast medium and used as controls, and
      flies supplemented with 1% C. sativus L. aqueous extract in standard medium were
      used as the experimental group. Following the ingestion of the various toxic
      compounds, the survival rate of the flies was determined. Cell viability and
      levels of reactive oxygen species (ROS) were detected using 7-amino-actinomycin D
      and dihydroethidium staining, respectively. The present study demonstrated that
      aqueous extracts of C. sativus L. may significantly increase the lifespan and
      survival rate of adult flies. Additionally, C. sativus L. may decrease epithelial
      cell death and ROS levels, resulting in improved intestinal morphology. These
      findings indicated that C. sativus L. had a protective effect against intestinal
      injury and may extend the lifespan of Drosophila. Therefore, the findings of the
      present study may improve the understanding of clinical researchers on the
      complex effects of C. sativus L. in intestinal disorders.

PMID- 27878269
TI  - Marmesin-mediated suppression of VEGF/VEGFR and integrin beta1 expression: Its
      implication in non-small cell lung cancer cell responses and tumor angiogenesis.
AB  - In the present study, we investigated the effects and molecular mechanism of
      marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non
      small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin
      abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type
      A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin
      were mediated by the inactivation of mitogenic signaling pathways and
      downregulation of cell signaling-related proteins including vascular endothelial
      growth factor receptor-2 (VEGFR-2), integrin beta1, integrin-linked kinase and
      matrix metalloproteinases-2. Furthermore, marmesin suppressed the expression and
      secretion of VEGF in both NSCLC cells, leading to inhibition of capillary-like
      structure formation in human umbilical vein endothelial cells. Collectively,
      these findings demonstrate the pharmacological roles and molecular targets of
      marmesin in regulating NSCLC cell responses and tumor angiogenesis.

PMID- 27878270
TI  - Alteration of histone H3 lysine 9 dimethylation in peripheral white blood cells
      of septic patients with trauma and cancer.
AB  - The present study aimed to investigate the clinical significance of histone
      methylation in sepsis. A total of 43 blood samples from trauma and esophageal
      cancer patients with or without sepsis were collected. Immunofluorescence
      staining of isolated peripheral white blood cells (WBCs) was conducted. Co
      stained 293T cells served as a reference, to allow the levels of histone
      methylation in different types of WBCs from patients to be determined.
      Immunostaining analyses revealed different levels of histone 3 lysine 9
      dimethylation (H3K9me2) in neutrophils (Neu), lymphocytes (Lym), and monocytes
      (Mon) from trauma patients. Compared with trauma patients, the levels of H3K9me2
      were elevated in the three types of WBCs from cancer patients. When combined with
      sepsis, trauma patients demonstrated increased H3K9me2 levels in Neu (P=0.0005)
      and Mon (P=0.0002), whereas cancer patients had a significant decrease of H3K9me2
      levels in the three types of WBCs (Neu, P=0.0003; Lym, P=0.007; Mon, P=0.007).
      The H3K9me2 alterations in patients with trauma and cancer were different with
      the occurrence of sepsis. A larger cohort study is warranted to explore the
      diagnostic significance and prognostic implications of altered histone
      methylation in septic patients.

PMID- 27878271
TI  - Estrogen is neuroprotective against hypoglycemic injury in murine N38
      hypothalamic cells.
AB  - Estrogen (E2) has been demonstrated to possess protective effects from
      hypoglycemic toxicity, particularly in the pancreas. In the central nervous
      system, several brain regions, such as the hypothalamus, are highly vulnerable to
      hypoglycemic injuries that may lead to seizures, coma, and mortality. The present
      study performed a novel in vitro assay of hypoglycemic injury to hypothalamic
      cells, and is the first study, to the best of our knowledge, to demonstrate that
      E2 protects hypothalamic cells from hypoglycemic toxicity. The toxic effects of
      hypoglycemia on hypothalamic cells in vitro was determined by performing cell
      counts, together with MTT and lactate dehydrogenase assays, using the N38 murine
      hypothalamic cell line. Following 24 and 48 h in hypoglycemic conditions, a 60
      and 75% reduction in cell number and mitochondrial function was observed, which
      reached 80 and ~100% by 72 and 96 h, respectively. E2 treatment prevented the
      hypoglycemia-induced loss in cell number and mitochondrial toxicity at 24 and 48
      h. However at 72 and 96 h of hypoglycemic conditions, the neuroprotective effects
      of E2 on cell number or mitochondrial function was not significant or not present
      at all. In order to determine whether E2 exerted its effects through the AKT
      signaling pathway, the expression of proline-rich AKT substrate of 40 kDa
      (PRAS40) was analyzed. No alterations in PRAS40 expression were observed when N38
      cells were exposed to hypoglycemic shock. From the biochemical and molecular data
      obtained, the authors speculated that E2 exhibits neuroprotective effects against
      hypoglycemic shock in hypothalamic cells, which dissipates with time. Despite
      demonstrating no significant effect on total AKT/PRS40 activity, it is possible
      that E2 may mediate these neuroprotective effects by upregulating the
      phosphorylated-AKT/pPRAS40 signaling pathway. The present study presented, to the
      best of our knowledge, the first in vitro model for hypoglycemic toxicity to
      hypothalamic cells, and provided evidence to suggest that E2 may protect
      hypothalamic cells from the damaging effects of hypoglycemia.

PMID- 27878272
TI  - miR-20b reduces 5-FU resistance by suppressing the ADAM9/EGFR signaling pathway
      in colon cancer.
AB  - Chemoresistance is a major obstacle to cancer therapy including that of colon
      cancer (CC). Although the dysregulation of many miRNAs has been implicated in 5
      fluorouracil (5-FU) resistance in CC cells, the specific role of miR-20b in
      chemoresistance has not been documented. In the present study, we first
      determined the expression of miR-20b by RT-PCR and the levels of a disintegrin
      and metalloprotease 9 (ADAM9) and epidermal growth factor receptor (EGFR) by
      western blotting in CC and adjacent non-cancerous tissues from 5-FU-sensitive or 
      resistant CC patients. Subsequently, 5-FU-sensitive (HCT116) and -resistant
      (HCT116-R) cells were obtained, and the levels of miR-20b, ADAM9 and EGFR were
      detected. Meanwhile, the 5-FU resistance of the cells was examined by assessing
      cell viability (by MTT assay) and apoptosis (by flow cytometry). After
      transfection of miR-20b into HCT116-R cells, drug resistance was reexamined. We
      then confirmed the relationship between miR-20b and ADAM9 by luciferase reporter
      assay. Finally, 5-FU resistance in HCT116 and HCT116-R cells was compared after
      transfection with miR-20b. Our results showed that miR-20b was expressed at lower
      levels in the 5-FU-resistant tissues and cells than in the 5-FU-sensitive tissues
      and cells. The opposite was the case for expression of ADAM9 and EGFR. In
      addition, we demonstrated that ADAM9 is a direct target of miR-20b and that miR
      20b decreased the 5-FU resistance of HCT116-R cells. Our findings suggest that
      miR-20b reduces 5-FU resistance to induce apoptosis in vitro by suppressing
      ADAM9/EGFR in CC cells.

PMID- 27878273
TI  - PI3K/Akt signaling is involved in the pathogenesis of bleomycin-induced pulmonary
      fibrosis via regulation of epithelial-mesenchymal transition.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized
      by chronic inflammation, fibroblast proliferation and extracellular matrix
      deposition. However, the molecular and cellular mechanisms underlying the
      pathogenesis of pulmonary fibrosis remain to be fully elucidated. The
      contribution of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)
      pathway in fibrotic processes remains to be investigated. The aim of the present
      study was to investigate the role of the PI3K/Akt pathway in pulmonary fibrosis.
      A rat model of pulmonary fibrosis was induced by intratracheal administration of
      bleomycin (BLM), and a specific PI3K/Akt inhibitor, LY294002, was used to assess
      the role of the PI3K/Akt pathway in fibrogenesis. The inflammatory and fibrotic
      alterations in the lung tissues were evaluated using histological staining and
      the hydroxyproline assay. In addition, the concentration of cytokines in
      bronchoalveolar lavage fluid and the expression of Akt, phosphorylated (p-)Akt,
      epithelial cadherin, alpha smooth muscle actin and vimentin in lung tissues. The
      data demonstrated that an increase in the expression levels of p-Akt was involved
      in the progression of pulmonary fibrosis and contributed to fibrogenesis.
      Administration of the Akt inhibitor significantly attenuated inflammation and
      fibrosis, which was accompanied by a reversal of lung fibrosis-associated
      epithelial-mesenchymal transition. Taken together, these observations suggest
      that the PI3K/Akt pathway serves a central role in the pathophysiology of lung
      fibrosis, and is a promising therapeutic target.

PMID- 27878274
TI  - Regulatory T cells exhibit neuroprotective effect in a mouse model of traumatic
      brain injury.
AB  - Traumatic brain injury (TBI) is a major health and socioeconomic problem as it is
      associated with high rates of mortality and morbidity worldwide. Regulatory T
      cells (Tregs) have been reported to reduce inflammatory response in several
      diseases, including myasthenia gravis, viral myocarditis and cerebral infarction.
      The present study investigated the role of Tregs in mediating neuro-protective
      effects in a mouse model of TBI. Initially, Treg levels were determined, and
      compared between the controlled cortical impact (CCI) model for moderate TBI and
      the sham group, by using flow cytometry and ELISA. Afterwards, the number of
      Tregs was upregulated (by injection) and downregulated (by depletion),
      respectively, to elucidate the effect of Tregs in the presence of an inflammatory
      reaction and a deficient neurological function and consequently, in the prognosis
      of TBI in the mouse. The expression of pro-inflammatory cytokines [tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, IL-6)] and anti-inflammatory
      cytokines [IL-10, transforming growth factor (TGF)-beta] in blood and brain
      tissues was also measured in the five groups: MUice receiving a saline injection,
      mice experiencing Treg depletion, small-dose (SD Tregs, 1.25x105), and mice
      receiving different doses of Tregs: Moderate-dose (MD Tregs, 2.5x105) and large
      dose (LD Tregs, 5x105), using ELISA and PCR. Co-cultures of Tregs and microglia
      were performed to evaluate the expression of pro-inflammatory cytokines and
      observe the interaction between the two types of cells. The regulation patterns
      in JNK-NF-kappaB pathway by Tregs were also evaluated by western blot analysis.
      Treg levels were significantly reduced in TBI mouse group on the 3rd day after
      TBI (P<0.05). In the mouse model of TBI, the expression of pro-inflammatory
      cytokines (TNF-alpha, IL-1beta, IL-6) was enhanced, while the expression of anti
      inflammatory cytokines (IL-10, TGF-beta) was reduced (P<0.05). Tregs exhibited a
      suppressive effect on inflammatory reactions. In the MD group, the activation of
      microglia cells was markedly inhibited, compared to the activation in SD and LD
      groups. The expression of ERK1/2, JNK1/2/3 and NK-kappaB was significantly
      downregulated in the MD group. The results indicated that Tregs exhibited
      significant neuro-protective effects, suppressing pro-inflammatory responses and
      promoting tissue repair after TBI injury in the mouse, specifically by
      deactivating the JNK-NF-kappaB pathway. The results of the study show that Tregs
      potentially participates in neuro-therapeutic approaches for TBI.

PMID- 27878275
TI  - Method for in vitro differentiation of bone marrow mesenchymal stem cells into
      endothelial progenitor cells and vascular endothelial cells.
AB  - Vascular development is a regulated process and is dependent on the participation
      and differentiation of many cell types including the proliferation and migration
      of vascular endothelial cells and differentiation of endothelial progenitor cells
      (EPCs) to mesodermal precursor cells. Thus, reconstitution of this process in
      vitro necessitates providing ambient conditions for generating and culturing EPCs
      in vitro and differentiating them to vascular endothelial cells. In the present
      study, we developed methods to differentiate bone marrow mesenchymal stem cells
      (MSC) into EPCs and to vascular endothelial cells. Bone marrow MSC from canines
      and human sources were differentiated in vitro in to EPCs. These EPCs were able
      to express a variety of endothelial markers following 7 days in culture. Further
      culturing led to the appearance of an increased number and proportion of
      endothelial cells. These cells were stable even after 30 generations in culture.
      There was a gradual loss of CD31 and increased expression of factor VIII, VEGFR
      and CD133. VEGF being highly angiogenic, helps in the vascular development. These
      results provide the basis for the possible development of vasculature in vitro
      conditions for biomedical applications and in vivo for organ/tissue
      reconstruction therapies.

PMID- 27878277
TI  - Synthetic paclitaxel-octreotide conjugate reverses the resistance of paclitaxel
      in A2780/Taxol ovarian cancer cell line.
AB  - The high mortality of ovarian cancer is partly due to the frequent resistance of
      ovarian cancer to current chemotherapy agents such as paclitaxel and platinum.
      Somatostatin analogue (SSTA) has been shown to inhibit the proliferation of some
      tumors through binding to somatostatin receptor (SSTR) and activation of Ras-,
      Rapl- and B-Raf-dependent extracellular signal-regulated kinase 2 (Erk2). It was
      reported that paclitaxel-octreotide conjugate (POC) exhibited enhanced tumor
      growth inhibition with reduced toxicity. In the present study, we prepared the
      POC and investigated its effects and mechanism for the reversal of drug
      resistance in paclitaxel-resistant ovarian cancer cell line. We demonstrated that
      treatment with POC led to more cell apoptosis than either paclitaxel or
      octreotide (OCT) alone. Moreover, the expression of multidrug resistance 1 (MDR1)
      and vascular endothelial growth factor (VEGF) mRNA, and protein decreased in a
      dose-dependent manner while the expression of SSTR remained stable following
      treatment with POC. Although the exact action, in vivo effects and pharmacologic
      kinetics of POC remain to be investigated, we have demonstrated the feasibility
      for the synthesis of POC, and more significantly, provided a potential approach
      to overcome the resistance of ovarian cancer against taxol. The findings also
      shed some new light on the mechanisms underlying the development of resistance to
      taxol by ovarian cancer cells.

PMID- 27878276
TI  - Expression pattern of HMGB1 and its association with autophagy in acute
      necrotizing pancreatitis.
AB  - High-motility group box protein 1 (HMGB1) has an important role in autophagy;
      however, its exact role in acute necrotizing pancreatitis (ANP) remains unknown.
      The present study aimed to investigate the expression pattern of HMGB1 in ANP,
      and to determine its association with autophagy. Sprague Dawley rats (weight,
      350+/-30 g, n=48) were randomly divided into control (n=12) and experimental
      (n=36) groups. Experimental rats were retrogradely injected with 5% sodium
      taurocholate into the biliopancreatic duct to induce ANP. Control rats received
      an equal amount of saline. Serum amylase levels were used to determine whether
      the model had been successfully generated. Autophagosomes in pancreatic acinar
      cells were observed under electron microscopy. The expression levels of HMGB1 and
      Beclin 1 were detected in pancreatic tissues by western blotting, quantitative
      polymerase chain reaction and immunohistochemistry. HMGB1 levels were also
      determined in the serum and in isolated nuclei. The results demonstrated that
      autophagy was detected at 3 h post-ANP induction; however, HMGB1 expression
      remained unaltered during the early stage (0-6 h; P>0.05). HMGB1 expression was
      significantly increased at 12 h, and was still increasing at 24 h (P<0.05).
      Notably, HMGB1 was increased in the nuclei compared with in the cytoplasm at 3-6
      h. Furthermore, serum HMGB1 levels began to increase at 3 h, and reached the
      highest levels at 24 h in the ANP group. In conclusion, in an ANP model, HMGB1
      was initially increased in the nuclei to initiate autophagy. Subsequently, it
      moved into the cytoplasm, where it interacted with Beclin 1 to enhance autophagy,
      and HMGB1 was released into the blood, leading to the deterioration of ANP.

PMID- 27878278
TI  - Alteration of epoxyeicosatrienoic acids in the liver and kidney of cytochrome
      P450 4F2 transgenic mice.
AB  - Arachidonic acid (AA) can be metabolized into 20-hydroxyeicosatetraenoic acid (20
      HETE) by omega-hydroxylases, and epoxyeicosatrienoic acids (EETs) by
      epoxygenases. The effects of EETs in cardiovascular physiology are vasodilatory,
      anti-inflammatory and anti-apoptotic, which are opposite to the function to 20
      HETE. However, EETs are not stable in vivo, and are rapidly degraded to the
      biologically less active metabolites, dihydroxyeicosatrienoic acids, via soluble
      epoxide hydrolase (sEH). Western blotting, reverse transcription-quantitative
      polymerase chain reaction and liquid chromatography tandem mass spectrometry were
      performed in order to determine target RNA and protein expression levels. In the
      present study, it was demonstrated that the disturbed renal 20-HETE/EET ratio in
      the hypertensive cytochrome P450 4F2 transgenic mice was caused by the activation
      of sEH and the repression of epoxygenase activity. In addition, 20-HETE showed an
      opposite regulatory effect on the endogenous epoxygenases in the liver and
      kidney. Given that 20-HETE and EETs have opposite effects in multiple disease,
      the regulation of their formation and degradation may yield therapeutic benefits.

PMID- 27878279
TI  - Zoledronic acid overcomes adriamycin resistance in acute myeloid leukemia cells
      by promoting apoptosis.
AB  - Zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, is widely used in
      metastatic bone disease. Previous studies indicate that ZOL has marked anti
      leukemia activity, however, the underlying mechanism of action remains to be
      elucidated. The present study aimed to explore the mechanism of the anti-leukemia
      effect of ZOL in leukemia cells. It was observed that ZOL inhibited the
      proliferation of HL-60 and adriamycin-resistant HL-60 (HL-60/A) cells using a WST
      8 assay. An Annexin V-propidium iodide indicated that ZOL induced apoptosis of
      the two cell types in a dose- and time-dependent manner. Hoechst 33342 staining
      was also used to verify the levels of apoptosis. The colony formation assay
      demonstrated that ZOL significantly inhibited colony formation capacity in acute
      myeloid leukemia (AML) cells. This was achieved by the induction of S-phase cell
      cycle arrest, downregulation of B-cell lymphoma 2 (Bcl-2) and upregulation of Bcl
      2 associated X protein and cleaved poly (ADP-ribose) polymerase. The results
      indicate that ZOL inhibited cell proliferation by inducing apoptosis via the
      mitochondrial apoptotic pathway and this anti-leukemic activity appeared notably
      enhanced in HL-60/A cells. As ZOL is already available for clinical use, these
      results indicate that it may be an effective addition to the chemotherapeutic
      strategies for AML.

PMID- 27878280
TI  - Loss of miR-638 promotes invasion and epithelial-mesenchymal transition by
      targeting SOX2 in hepatocellular carcinoma.
AB  - Aberrant expression of microRNAs has been identified as regulators of biological
      processes of hepatocellular carcinoma (HCC) by negatively regulating protein
      coding mRNAs. Several studies have demonstrated that miR-638 expression was
      dysregulated in various human cancers. However, the clinical significance and
      underlying mechanisms of miR-638 involved in HCC remain to be elucidated. Herein,
      we confirmed that a reduced miR-638 expression was present in HCC tissues and
      cell lines. Our clinical analysis revealed that the downregulated miR-638
      expression was significantly correlated with poor prognostic features including
      high Edmondson-Steiner grade, venous infiltration and advanced tumor-node
      metastasis (TNM) stage. Moreover, we demonstrated that miR-638 was a novel
      independent prognostic marker for predicting 5-year survival of HCC patients.
      Functionally, overexpressed miR-638 expression inhibited cell migration and
      invasion, while downregulated miR-638 reversed the effect. In addition, miR-638
      could regulate SOX2 by directly binding to its 3'-UTR. Alternation of SOX2
      expression at least partially abolished the migration and invasion effects of miR
      638 on HCC cells. Aberrant miR-638 expression could regulate the expression level
      of epithelial-to-mesenchymal transition markers in vitro and in vivo by
      modulating SOX2 expression. In conclusion, our data indicated that miR-638
      functioned as a tumor suppressor gene and play a critical role in the development
      of HCC.

PMID- 27878281
TI  - Etomidate inhibits nuclear factor-kappaB through decreased expression of
      glucocorticoid receptor in septic rats.
AB  - The present study aimed to investigate the effect of etomidate administered prior
      to or following cecal ligation and puncture (CLP) on the expression of
      glucocorticoid receptor (GR) and lymphocyte apoptosis in septic rats. Right
      jugular vein catheterization was performed on female Sprague-Dawley rats under
      isoflurane anesthesia, and CLP surgery was performed to induce sepsis 3 days
      following catheterization. The rats were randomly divided into five groups. All
      groups were infused with 2 ml of either etomidate or 50/00 dimethyl sulfoxide
      (DMSO) at 1 ml/h for 2 h from 6 h post-surgery. The sham group received abdominal
      sham surgery and infusion with DMSO; the CLP control group received infusion with
      DMSO. Treatment group A received infusion with 2 mg/kg etomidate; group B
      received 0.6 mg/kg etomidate following CLP and an infusion of 2 mg/kg etomidate.
      Group C received 0.6 mg/kg etomidate 24 h prior to CLP and post-surgical
      etomidate infusion. The 10-day survival rates of the rats in the CLP, A, B and C
      groups were 60, 50, 55 and 40%, respectively. The serum mRNA expression levels of
      tumor necrosis factor-alpha, GR and glucocorticoid-induced leucine zipper were
      detected by reverse transcription-quantitative polymerase chain reaction, the
      abundance of inhibitor of nuclear factor (NF)-kappaB-alpha was measured by
      western blotting, and the apoptotic rates of the splenic lymphocytes were
      determined using flow cytometry. The results suggested that etomidate inhibited
      NF-kappaB by decreasing the expression of GR in the septic rats. The increased
      apoptosis of lymphocytes induced by etomidate may lead to a poor outcome during
      sepsis.

PMID- 27878282
TI  - The importance of mitochondrial folate enzymes in human colorectal cancer.
AB  - Folate plays a pivotal role in the one-carbon metabolism needed for methylation
      reactions, nucleotide synthesis, and DNA repair. Although folate metabolism was
      recently shown to be associated with carcinogenesis in some solid tumors, the
      importance of folate metabolism in colorectal cancer remains unclear. In the
      present investigation we found that expression of three mitochondrial folate
      metabolic enzymes, serine hydroxymethyl transferase (SHMT2),
      methylenetetrahydrofolate dehydrogenase (MTHFD2) and aldehyde dehydrogenase 1
      family member L2 (ALDH1L2), were upregulated in human colorectal tumor tissues
      compared to normal tissues. Colorectal cancer tissue samples were obtained from
      117 consecutive patients. We evaluated the expression of the enzymes with
      immunohistochemical analysis and determined their relevance to
      clinicopathological characteristics and prognosis. Rates of recurrence-free
      survival (RFS) and overall survival (OS) in patients with high expression of
      SHMT2, MTHFD2 and ALDH1L2 tended to be lower than in patients with low expression
      of SHMT2, MTHFD2 and ALDH1L2 (P=0.446 and P=0.337, P=0.099 and P=0.064, P=0.178
      and P=0.257, respectively). Notably, the combined high expression of SHMT2,
      MTHFD2 and ALDH1L2 (triple high) was more highly associated with poor prognosis
      than the individual expression levels (RFS; P=0.004 and OS; P=0.037). A
      multivariate analysis showed that triple high expression was independently
      associated with RFS (P=0.017). These findings suggested that mitochondrial folate
      metabolic enzymes could provide a potential therapeutic strategy for treating
      colorectal cancer.

PMID- 27878283
TI  - HES5 promotes cellular proliferation of non-small cell lung cancer through STAT3
      signaling.
AB  - HES5 is a transcription factor activated downstream of the Notch pathway and
      regulates cell differentiation in multiple tissues. Disruption of its normal
      expression has been associated with developmental diseases and cancer. But its
      role in non-small cell lung cancer (NSCLC) remains elusive. Western blot analysis
      and immunohistochemistry assays demonstrated that HES5 expression was frequently
      increased in NSCLC tumor tissues and cell lines. Moreover, immunohistochemistry
      analysis revealed that upregulation of HES5 expression was positively correlated
      with a more invasive tumor phenotype and poor prognosis. Immunoprecipitation
      assay indicated that HES5 directly interacted with STAT3. In addition, depletion
      of HES5 resulted in inhibited phosphorylation of STAT3 and decreased expression
      of the downstream genes. In vitro studies, using serum starvation-refeeding
      experiment and HES5-siRNA transfection assay demonstrated that HES5 expression
      promoted proliferation of NSCLC cells, while HES5 knockdown caused growth arrest
      of cell cycle at G0/G1 phase, decreased rate of colony formation and alleviated
      cellular apoptosis. Taken together, out data have delineated that HES5 might
      contribute to the proliferation of NSCLC by STAT3 signaling.

PMID- 27878284
TI  - Antitumor effect of the combination of manumycin A and Immodin is associated with
      antiplatelet activity and increased granulocyte tumor infiltration in a 4T1
      breast tumor model.
AB  - Manumycin A is a natural antibiotic isolated from Streptomyces parvulus with
      broad range of biological activities including antineoplastic activity in several
      in vitro and in vivo cancer models. Immodin [dialyzable leukocyte extract (DLE)]
      is a dialysate released from disintegrated blood leukocytes of healthy donors
      which exerts immunonormalizing effects on cell-mediated immune responses. The aim
      of the present study was to explore the antitumor potential of the combination of
      manumycin A and Immodin in an experimental breast cancer model. Experiments were
      carried using a 4T1 tumor-bearing BALB/c mouse model. Survival analysis, tumor
      growth, hematological and biochemical profiles, leukocyte differential,
      phagocytic activity of leukocytes and histology of the primary tumor were
      examined. The combination treatment suppressed the tumor growth and prolonged the
      survival of tumor-bearing mice, decreased the number of monocytes, plateletes and
      plateletcrit in peripheral blood of the tumor-bearing mice and increased the
      infiltration of neutrophils and eosinophils in the primary tumor. Moreover,
      individual therapies enhanced the phagocytic activity of monocytes and
      neutrophils. These findings demonstrate the antitumor effect of the combination
      of manumycin A and Immodin in 4T1 tumor-bearing mice associated with strong
      antiplatelet activity and innate immunity activation.

PMID- 27878285
TI  - Trichostatin A increases radiosensitization of tongue squamous cell carcinoma via
      miR-375.
AB  - Trichostatin A (TSA), a histone deacetylase inhibitor, is used as an anti
      carcinogenic and radiosensitizing agent in various cancers. However, the role and
      mechanism underlying its radiosensitization of tongue squamous cell carcinoma
      (TSCC) remains unclear. Thus, in this study we aimed to confirm the promotion of
      miR-375 expression by TSA, and to investigate the effects of TSA and miR-375 in
      the radiosensitivity of TSCC cells. The results showed that TSA had significant
      radiosensitizing effects on TSCC cells and miR-375 overexpression had effects
      similar to TSA in sensitizing these cells to radiotherapy. By contrast, miR-375
      knockdown attenuated apoptosis induced by radiation combined with TSA.
      Mechanistically, the histone acetylation status of the miR-375 promoter region
      was increased by TSA, resulting in the upregulation of miR-375, which led to a
      decline of PDK1 and phosphorylated AKT. Taken together, our data suggest that TSA
      increases the radiosensitization and apoptosis in TSCC cells at least partially
      via miR-375, and TSA or miR-375 in combination with radiotherapy may provide a
      valuable approach for the treatment of TSCC.

PMID- 27878286
TI  - Obesity-associated miR-148a is regulated by cytokines and adipokines via a
      transcriptional mechanism.
AB  - Our previous study revealed that miR-148a, a cyclic adenosine monophosphate
      response element binding protein-modulated microRNA that promotes adipocyte
      differentiation by inhibiting Wnt1, is a biomarker of obesity in human subjects
      and a mouse model. The present study investigated the expression of miR-148a in
      human adipose tissue-derived mesenchymal stem cells (hMSCs-Ad) in response to
      inflammatory cytokines and adipokines to clarify its underlying mechanism. miR
      148a expression was detected using reverse transcription-quantitative polymerase
      chain reaction analysis and its promoter activity was detected with a luciferase
      assay. miR-148a expression levels decreased when differentiated hMSCs-Ad were
      exposed to inflammatory cytokines or adipokines, which suggested that miR-148a
      may be important in adipocyte metabolism and inflammation. Furthermore, the
      promoter activity of miR-148a decreased following treatment of cells with
      inflammatory cytokines or adipokines. The results of the present study indicated
      a novel role of miR-148a in adipocyte inflammation; therefore, miR-148a may be
      involved in obesity complications via its own underlying transcriptional
      mechanism.

PMID- 27878287
TI  - PDK1 promotes tumor cell proliferation and migration by enhancing the Warburg
      effect in non-small cell lung cancer.
AB  - Tumor cells prefer glycolysis (Warburg effect) during the proliferation and
      metastasis. The precise mechanism remains largely unknown. Here, we demonstrated
      that pyruvate dehydrogenase kinase 1 (PDK1) was a critical enzyme that functioned
      as an oncogene to promote non-small cell lung cancer (NSCLC) growth and
      metastasis. We discovered that PDK1 expression was significantly upregulated in
      NSCLC tissues and correlated with advanced T stage. Moreover, high expression of
      PDK1 was an independent prognostic factor of NSCLC. Ectopic overexpression of
      PDK1 promoted cell proliferation and inhibited apoptosis. Also it was shown that
      PDK1 increased the cell mobility when Transwell assay was performed. Further
      experiments indicated that PDK1 had a central role in metabolic reprogramming by
      phosphorylating pyruvate dehydrogenase, leading to enhanced Warburg effect.
      Collectively, our data reveal a new function for PDK1, which could be used to
      indicate the prognosis of NSCLC, and provide targeted therapeutic strategy for
      clinical treatment.

PMID- 27878288
TI  - MicroRNA-6826 and -6875 in plasma are valuable non-invasive biomarkers that
      predict the efficacy of vaccine treatment against metastatic colorectal cancer.
AB  - Various vaccine treatments against metastatic colorectal cancer have been
      developed and applied. However, to improve the efficacy of immunotherapy,
      biomarkers that can predict the effects are needed. It has been reported that
      various microRNAs (miRNAs) in peripheral blood may be useful as non-invasive
      biomarkers. In this study, miRNAs influencing the efficacy of vaccine treatment
      were screened for in a microarray analysis of 13 plasma samples that were
      obtained from patients prior to vaccine treatment. To validate the screening
      results, real-time RT-PCR was performed using 93 plasma samples obtained from
      patients prior to vaccine treatment. Four candidate miRNAs were selected
      according to the results of the comprehensive analysis of miRNA expression, which
      were ranked using the Fisher criterion and the absolute value of the log2 ratio
      in the screening analysis. The validation analysis showed that in the HLA-A*2402
      matched patient group (vaccine-treated group), patients with a high expression of
      plasma miR-6826 had a poorer prognosis than those with a low expression
      (P=0.048). In contrast, in the HLA-A*2402-unmatched patient group (control
      group), there was no difference between the patients with high or low plasma miR
      6826 expression (P=0.168). Similar results were obtained in the analysis of miR
      6875 (P=0.029 and P=0.754, respectively). Moreover, multivariate analysis of the
      Cox regression model indicated that the expression of miR-6826 was the most
      significant predictor for overall survival (P=0.003, hazard ratio, 3.670). In
      conclusion, plasma miR-6826 and miR-6875 may be predictive biomarkers for a poor
      response to vaccine treatment. Although further clarification is needed regarding
      the functions of miR-6826 and miR-6875 and their relationship to immune-related
      molecules, plasma miR-6826 and miR-6875 may be useful negative biomarkers for
      predicting the efficacy of vaccine treatment.

PMID- 27878289
TI  - Oncogenic function of Plac1 on the proliferation and metastasis in hepatocellular
      carcinoma cells.
AB  - Placenta-specific protein 1 (Plac1), which is selectively expressed in the
      placental syncytiotrophoblast in adult normal tissues, plays an essential role in
      normal placental and embryonic development. Accumulating evidence suggests that
      enhanced Plac1 expression is closely associated with the progression of human
      cancer. Whether Plac1 contributes to the pathophysiology of hepatocellular
      carcinoma (HCC) remains unclear. In the present study, our data revealed that the
      expression of Plac1 in human HCC tissues was upregulated, which significantly
      correlated with metastasis of HCC. Knockdown of Plac1 by small interfering RNA
      (siRNA) in Bel-7402 and HepG2 cells resulted in decreasing tumor cell
      proliferation and increasing apoptosis, which implied the oncogenic potential of
      Plac1. Moreover, silencing of Plac1 induced G1 cell cycle arrest through
      suppression of cyclin D1 and CDK4 expression. Furthermore, depletion of Plac1
      repressed epithelial-mesenchymal transition (EMT), with decreased cell migration
      and invasion, supporting upregulated E-cadherin expression and downregulated
      vimentin, twist and snail expression that characterize EMT. Further study
      suggested that decreased Plac1 expression attenuated the phosphorylation of Akt.
      These findings have uncovered that Plac1 plays a pivotal role in the progression
      of HCC, and may serve as a novel therapeutic target for HCC.

PMID- 27878290
TI  - (-)-Oleocanthal exerts anti-melanoma activities and inhibits STAT3 signaling
      pathway.
AB  - Tumor angiogenesis, growth and metastasis are three closely related processes. We
      therefore explored the effects of (-)-oleocanthal (OC) on the three processes in
      melanoma and investigated underlying mechanisms. In vitro, OC suppressed
      proliferation, migration, invasion and induced apoptosis in melanoma cells. In
      addition, OC inhibited proliferation, migration, invasion and tube formation in
      human umbilical vascular endothelial cells. In vivo, it exhibited potent activity
      in suppressing tumor growth in a subcutaneous xenograft model. Furthermore, OC
      suppressed proliferation and angiogenesis as measured by immunohistochemical
      staining of Ki-67 and CD31. In addition, OC was found to inhibit metastasis of
      melanoma in a lung metastasis model. Mechanistically, OC significantly suppressed
      signal transducer and activator of transcription 3 (STAT3) phosphorylation,
      decreased STAT3 nuclear localization and inhibited STAT3 transcriptional
      activity. OC also downregulated STAT3 target genes, including Mcl-1, Bcl-xL, MMP
      2, MMP-9, VEGF, which are involved in apoptosis, invasion and angiogenesis of
      melanoma. These results support further investigation of OC as a potential anti
      melanoma drug.

PMID- 27878291
TI  - Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system
      promotes the cell apoptosis of CD133+ ovarian cancer stem cells.
AB  - Cancer stem cells are a small subset of cancer cells that contribute to cancer
      progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+)
      ovarian cancer cells have been identified as ovarian cancer stem cells.
      Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer
      treatment. In the present study, we aimed to develop a new gene therapy to
      specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We
      used the Cre/LoxP system to augment the selective expression of the truncated Bid
      (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The
      adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the
      CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of
      the CMV promoter were successfully constructed using the Cre/LoxP switching
      system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre
      selectively induced tBid overexpression, which inhibited cell growth and
      triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP
      system-mediated tBid overexpression activated the pro-apoptotic signaling pathway
      and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem
      cells. Furthermore, in xenograft experiments, co-infection with the two
      recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted
      cell apoptosis in tumor tissues. Taken together, the present study provides
      evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP
      system can effectively eliminate CD133+ ovarian cancer stem cells, representing a
      novel therapeutic strategy for the treatment of ovarian cancer.

PMID- 27878292
TI  - BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death.
AB  - The B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) protein is activated in
      various types of tumors and associated with cancer development and tumor
      progression. However, the working role of BMI-1 in cellular signaling is not
      understood completely. In this study, we revealed one possible biologic mechanism
      of BMI-1 in cancer progression in vitro using a human ovarian tumor cell system.
      Suppressor of MEK1 (sMEK1), a pivotal regulator involved in the cellular
      biological response mechanism, was identified as a BMI-1-binding protein. Ectopic
      expression of BMI-1 activated cell growth by reducing sMEK1-stimulated apoptotic
      cell death and suppressing p21, p27 and p53 expression, while enhancing cyclin
      D1, CDK4 and Bcl-2 expression. The effect of BMI-1 on cell cycle and apoptotic
      regulatory proteins was also confirmed via silencing of BMI-1 expression.
      Subsequently, the promoter activities of p21 and p53 were inactivated
      significantly. However, BMI-1 overexpression noticeably increased Bcl-2 and NF
      kappaB activities. In addition, BMI-1 activated the PI3K/mTOR/4E-BP1 signaling
      pathways, and sMEK1 significantly inhibited BMI-1-stimulated oncogenesis. These
      insights provide evidence that BMI-1 activates cell growth and suppresses
      apoptosis. Collectively, our data indicate that BMI-1 plays a pivotal role in the
      progression of ovarian cancer, thus representing a novel target for antitumor
      therapy of ovarian cancer.

PMID- 27878293
TI  - Stathmin1 overexpression in hypopharyngeal squamous cell carcinoma: A new
      promoter in FaDu cell proliferation and migration.
AB  - Stathmin1, a microtubule-destabilizing phosphoprotein, is considered to play a
      crucial role in regulating cellular microtubule dynamics and controlling mitosis.
      Previous studies have showed that STMN1 is highly expressed in many human
      malignancies and is related to development, invasion and metastasis of tumors.
      However, its expression pattern, clinical performance and functional roles in
      hypopharyngeal squamous cell carcinoma (HSCC) have not been addressed. In this
      study, we found that STMN1 was significantly elevated in HSCC and its expression
      level was correlated with poor differentiation (P<0.001), clinical stage
      (P<0.001), large tumor size (P=0.001) and lymph node metastasis (P=0.008). A
      positive correlation between STMN1 and Ki-67 expression was also exhibited. High
      STMN1 expression predicted poor survival. Furthermore, we found that knockdown of
      STMN1 by siRNAs inhibited the FaDu cell proliferation and migration. Moreover,
      decreased STMN1 expression in FaDu cells reversed the acquisition of EMT
      phenotype by upregulating E-cadherin, as well as reduced vimentin expression at
      protein and mRNA levels. These results suggested that STMN1 plays an important
      role in proliferation and migration of HSCC and may be used as a potential
      prognostic biomarker or therapeutic target of HSCC.

PMID- 27878294
TI  - Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast
      cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231
      cells.
AB  - Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L.
      which has been widely used as a diuretic and a diaphoretic in Traditional Chinese
      Medicine. In the present study, the authors investigated the effects of
      arctigenin on tumor migration and invasion in aggressive human breast cancer
      cells. The MTT assay results showed that arctigenin did not show a significant
      cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound
      healing migration and Boyden chamber invasion assays demonstrated that arctigenin
      significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells.
      Furthermore, gelatin zymography results showed that arctigenin reduced the
      activity of MMP-2 and MMP-9. Western blot analysis results demonstrated that the
      expression of MMP-2, MMP-9 and heparanase proteins was significantly
      downregulated following the treatment of arctigenin. Finally, the antiangiogenic
      activity of arctigenin was also examined by the chick embryo chorioallantoic
      membrane (CAM) assay. Arctigenin treatment significantly inhibited angiogenesis
      in the CAM. In conclusion, the results revealed that arctigenin significantly
      inhibited the migration and invasion of MDA-MB-231 cells by downregulating MMP-2,
      MMP-9 and heparanase expression. However, further studies are still necessary to
      investigate the exact mechanisms involved and to explore signal transduction
      pathways to better understand the biological mechanisms.

PMID- 27878295
TI  - Silencing of the long non-coding RNA NEAT1 suppresses glioma stem-like properties
      through modulation of the miR-107/CDK6 pathway.
AB  - Developing novel strategies against glioma remains a significant challenge. Long
      non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) significantly
      contributes to the progression of many human cancers, while glioma stem cells
      (GSCs) are believed to be responsible for tumor progression. However, whether
      NEAT1 alters the stem-like properties of GSC cells remains unknown. Using
      microbeads, CD133+ cells were isolated and were found to possess glioma stem cell
      properties. Using siRNA, NEAT1 was knocked down in the sorted CD133+ U87 glioma
      cells. We found higher NEAT1 RNA expression in CD133+ human glioma primary
      culture stem cells and CD133+ U87 cells via RT-PCR. Moreover, NEAT1 knockdown in
      the CD133+ U87 cells resulted in decreased colony formation, increased G1 cell
      cycle arrest and apoptosis. In addition, these effects were accompanied by miR
      107 activation and inactivation of CDK6 protein. These results strongly suggest
      that NEAT1 knockdown suppresses stem-like properties in glioma cells by
      modulating the miR-107CDK6 pathway. Targeting NEAT1 may provide a novel
      therapeutic opportunity for developing a relapse-free treatment of glioma
      patients.

PMID- 27878296
TI  - Pseudolaric acid B inhibits the secretion of hepatitis B virus.
AB  - High hepatitis B virus (HBV) load and chronic hepatitis B infection increase the
      risk of developing hepatocellular carcinoma (HCC), and is also associated with
      recurrence of HBV-related HCC. The aim of the present study was to investigate
      whether pseudolaric acid B (PAB), a diterpene acid isolated from the root and
      trunk bark of Pseudolarix kaempferi Gordon (Pinaceae), has an inhibitory role on
      the HBV secretion in HBV-related HCC. By detecting HBV surface antigen (HBsAg) by
      ELISA it was found that PAB inhibited HBV secretion in HepG2215 compared to
      control group, but did not decrease the intracellular HBV level, and the results
      were repeated in HepG2 cell transfect with HBV gene. Therefore, our results
      proved that PAB had the ability to inhibit HBV secretion. Moreover, it was shown
      that HepG2215 cells with HBV gene accumulated more in G0/G1 phase than HepG2
      cells without HBV gene through detecting cell cycle distribution by flow
      cytometry, which indicated that HBV replication might favor the cell cycle
      environment of G0/G1 phase. However, HepG2 cells entered G2/M phase earlier than
      HepG2215 when PAB treatment induced G2/M arrest, therefore, HBV retarded the
      entry of G2/M to sustain the status of G0/G1 phase, while PAB finally changed the
      cell cycle environment favored by HBV virus. In addition, PAB also induced
      HepG2215 cell apoptosis, which would be helpful to kill the cells infected by HBV
      and help for devouring HBV by macrophage. Therefore, PAB inhibited HBV secretion
      through apoptosis and cell cycle arrest. The present findings contribute to a
      future potential chemotherapeutic drug in the treatment of HBV-related HCC.

PMID- 27878297
TI  - Hydroxyproline-containing collagen peptide derived from the skin of the Alaska
      pollack inhibits HIV-1 infection.
AB  - The human immunodeficiency virus (HIV) is a lentivirus that results in acquired
      immunodeficiency syndrome (AIDS). HIV treatment involving chemical therapeutic
      agents has improved the quality of life of HIV/AIDS patients. The present study
      demonstrates that a hydroxyproline-containing marine collagen peptide (APHCP)
      derived from Alaska pollack inhibits HIV-1 infection in the MT-4 human T cell
      line. APHCP inhibited HIV-1IIIB-induced cell lysis, syncytia formation, reverse
      transcriptase activity and viral p24 production at non-cytotoxic concentrations;
      however, APHCP did not inhibit HIV-2ROD infection in MT-4 cells. This suggests
      that the anti-HIV activity of APHCP is specific to HIV-1. In addition,
      substitution of hydroxyproline residues in APHCP with prolines impaired its anti
      HIV-1 activity, suggesting that the hydroxyl group of hydroxyprolines is required
      for the anti-HIV-1 activity of APHCP. These results suggested that the marine
      peptide APHCP may be a novel drug candidate in the development of next-generation
      therapeutic agents for the treatment of HIV/AIDS.

PMID- 27878298
TI  - TRAIL overexpression co-regulated by Egr1 and HRE enhances radiosensitivity of
      hypoxic A549 cells depending on its apoptosis inducing role.
AB  - Ionizing radiation can upregulate the expression levels of TRAIL and enhance
      tumor cell apoptosis. While Early growth response 1 (Egr1) gene promoter has
      radiation inducible characteristics, the expression for exogenous gene controlled
      by Egr1 promoter could be enhanced by ionizing radiation, but its efficiency is
      limited by tissue hypoxia. Hypoxia response elements (HREs) are important hypoxic
      response regulatory sequences and sensitivity enhancers. Therefore, we chose
      TRAIL as the gene radiotherapy to observe whether it is regulated by Egr1 and HER
      and its effects on A549 cells and its mechanism. The pcDNA3.1-Egr1-TRAIL (pc-E
      hsT) and pcDNA3.1-HRE/Egr1-TRAIL (pc-H/E-hsT) plasmids containing Egr1-hsTRAIL
      and HRE/Egr1-hsTRAIL were transfected into A549 cells, the cells were treated by
      hypoxia and radiation. The TRAIL mRNA in the cells and protein concentration in
      the culture supernatants were measured by RT-PCR and ELISA, respectively. Mean
      lethal dose D0 value was evaluated with colony forming assay. The cell apoptotic
      rates were analyzed by FCM and TUNEL assay. Expression of DR4, DR5 and cleaved
      caspase-3 proteins were analyzed by western blotting. It showed that TRAIL mRNA
      expression and TRAIL concentration all significantly increased under hypoxia
      and/or radiation. D0 value of pc-H/E-hsT transfected cells under hypoxia was
      lowest, indicating more high radiosensitivity. Hypoxia could not cause the pc-E
      hsT transfected cell apoptotic rate increase, but there were promoting effects in
      pc-H/E-hsT transfected cells. DR4 had not obvious change in pc-E-hsT and pc-H/E
      hsT transfected cells under normoxic and hypoxic condition, otherwise, DR5 and
      cleaved caspase-3 increased mostly in pc-H/E-hsT transfected cells under hypoxic
      condition. TRAIL overexpression was co-regulated by Egr1 and HRE. TRAIL might
      promote hypoxic A549 cell radiosensitivity and induce apoptosis depending on DR5
      to caspase-3 pathways.

PMID- 27878299
TI  - Antioxidant and antitumor activities of Capparis spinosa L. and the related
      mechanisms.
AB  - The 'ethnodrug' Capparis spinosa L. has several pharmacological activities.
      First, it was found in previous experiments that an ethyl acetate extract of
      Capparis spinosa L. (CSE) exhibited antioxidant activity. In order to further
      research this finding, the present study investigate the blood biochemical
      indices, injury, energy metabolism, oxidative damage and mitochondrial membrane
      potential (Deltapsim) level of cardiac cells to study the effect of CSE on
      doxorubicin-induced cardiac toxicity. CSE had protective effects on the cardiac
      toxic effect of doxorubicin, and decreased the activity of lactic dehydrogenase
      (LDH) and creatine kinase (CK). CSE increased the ability of myocardial tissue to
      scavenge free radicals, inhibited lipid peroxidation, increased recovery activity
      of antioxidant enzymes, adjusted the energy metabolism of myocardial tissue,
      inhibited the generation of a large number of ROS in the cells, raised the level
      of Deltapsim, and improved the metabolism of free radicals. CSE demonstrated
      protective effects on doxorubicin-induced myocardial damage. Second, the
      quaternary ammonium hydroxide of Capparis spinosa L. (CSQAH) was found to possess
      antitumor activity, such as antiproliferative and apoptosis-induced effects on
      HepG2 cells. We investigated the regulatory mechanism of HepG2 apoptosis induced
      by CSQAH. Laser scanning confocal microscope and Fluo-3/AM staining were utilized
      to detect the Ca2+ concentration in the HepG2 cells. A microplate reader was used
      to measure the changes in Ca2+-Mg2+-ATP enzyme. Then, flow cytometry was applied
      to analyze the activity of ROS and the expression levels of Bcl-2 and Bax. As a
      result, different concentrations of CSQAH increased the concentration of Ca2+ in
      the cytoplasm in a dosage-dependent manner. CSQAH decreased the Ca2+-Mg2+-ATPase
      activity in the HepG2 cells. The levels of ROS in the CSQAH groups were
      significantly higher than the level in the control group. Flow cytometric
      analysis showed that the Bcl-2 expression levels in the CSQAH-treated groups were
      downregulated, while Bax expression levels were upregulated, and the effects were
      dosage-dependent. The regulatory mechanism of HepG2 cell apoptosis induced by
      CSQAH involved the increase in Ca2+ concentration and ROS levels, a decrease in
      Ca2+-Mg2+-ATPase activity in the HepG2 cells, and downregulation of anti
      apoptotic Bcl-2 expression, and upregulation of apoptotic Bax expression. In
      summary, the present study demonstrated the antioxidant and antitumor activities
      of CSE which may suppress tumor growth and alleviate the side-effects of DOX,
      which may facilitate tumor treatment in a dual manner.

PMID- 27878300
TI  - Induction of DNA damage and apoptosis in human leukemia cells by efavirenz.
AB  - As part of the efforts to drug repurposing, some HIV drugs have recently been
      identified to exert anticancer effects. Selected nucleoside analogues of
      nucleosidic reverse-transcriptase inhibitors (NRTIs) have been shown to interfere
      with RNA transcription of HI viruses as well as with the replication of DNA in
      cancer cells. Non-nucleosidic reverse transcriptase inhibitors (NNRTIs) are
      believed to have less effects on human DNA replication and, thus, on cancer cell
      proliferation. Assessment of the effect of the NNRTI efavirenz in human cancer
      cells, however, revealed a high sensitivity of leukemia cells to this agent at
      pharmacologically relevant concentrations of less than 10 ug/ml. Cell death
      induced by efavirenz was caused by apoptosis, as shown by FACScan analysis
      (Annexin binding) and western blot analysis (cleavage of caspases and PARP).
      Western blot analyses also revealed a pronounced activation and phosphorylation
      of the DNA damage marker proteins p53, chk2 and H2AX, indicating DNA replication
      and genomic integrity as primary targets of efavirenz in leukemia cells.

PMID- 27878301
TI  - Long non-coding RNA TUC338 is functionally involved in sorafenib-sensitized
      hepatocarcinoma cells by targeting RASAL1.
AB  - Development of novel targeted therapy holds promise for conquering chemotherapy
      resistance, one of major hurdles in current liver cancer treatment. We found that
      long non-coding RNA TUC338 is involved in the development of hepatocellular
      carcinoma (HCC) and sorafenib resistance. HCC cell lines were transfected with
      siTUC338, then cell proliferation and invasion ability were investigated by MTT
      and Transwell assay. Sorafenib resistance HepG2 cells were generated to test the
      role of TUC338 in sorafenib sensitivity. Intratumoral delivering of siTUC338 was
      used to analyze the sorafenib treatment response in HepG2/Sor xenografts in vivo.
      Higher levels of TUC338 were found both in HCC tissues and cell lines, knockdown
      of TUC338 was accompanied with increased expression of RASAL1 in HCC cell line
      with increased proliferation and invasion ability, knockdown of TUC338 could
      activate the RASAL1 pathway and inhibit tumor growth genes by directly targeting
      RASAL1 3'-UTR. Furthermore, knockdown of TUC338 in HepG2 sorafenib sensitized its
      reaction to the treatment of sorafenib, which was accompanied by increased
      expression RASAL1; intratumoral delivering of siTUC338 could also restore
      sorafenib treatment response in HepG2/Sor xenografts in vivo. These findings
      provide direct evidence that the TUC338/RASAL1 axis might play an essential role
      in sorafenib-resistance of liver cancer cells, suggesting the signaling cohort
      could serve as a novel therapeutic target for the treatment of chemotherapy
      resistant liver cancer.

PMID- 27878302
TI  - Triptolide inhibits tumor growth by induction of cellular senescence.
AB  - Cellular senescence, an irreversible growth arrest of cells, is involved in
      protection against cancer. Triptolide (TPL) plays an important role in
      immunosuppressive, anti-fertility, anti-cystogenesis and anticancer activities.
      However, effect and mechanism of TPL on cellular senescence-associated antitumor
      is rarely reported. Herein HepG2 cells were used to explore the effect of TPL on
      tumor growth and cellular senescence. We showed that TPL inhibited tumor cell
      proliferation and growth in vitro and in vivo, accelerated cellular senescence
      and arrested cells at G0/G1 phase. We further demonstrated that TPL accelerated
      HepG2 cell senescence by regulating the AKT pathway. In addition, TPL could also
      enhance cellular senescence and inhibit tumor growth by negatively regulating
      human telomerase reverse transcriptase (hTERT) signaling pathway. These findings
      reveal a regulatory mechanism of TPL on cellular senescence, indicating that TPL
      promotes HepG2 cell senescence through AKT pathway and hTERT pathway
      simultaneously. Altogether, TPL-induced senescence can be regarded as a promising
      strategy for anticancer therapy and drug development.

PMID- 27878303
TI  - Neuroprotective effects of vitexin against isoflurane-induced neurotoxicity by
      targeting the TRPV1 and NR2B signaling pathways.
AB  - Vitexin is a bioactive compound extracted from hawthorn leaves, which reduces
      blood pressure and has anti-inflammatory and potential anticancer effects.
      However, the mechanisms underlying the protective effects of vitexin against
      isoflurane-induced neurotoxicity remain elusive. Therefore, the aim of the
      present study was to investigate these mechanisms further. Sprague Dawley rats
      received 1.4% isoflurane in a 100% oxygen environment for 2 h. Human PC12
      pheochromocytoma neurosecretory cells were exposed to 2% isoflurane for 12 h
      before they were treated with 1, 10 or 100 uM vitexin for a further 24 h. Vitexin
      inhibited the isoflurane-induced cell cytotoxicity and weakened isoflurane
      induced neuroinflammation and oxidative stress pathways in PC12 cells. In
      addition, treatment with vitexin suppressed isoflurane-induced caspase-3
      activation and increased beta-secretase 1 levels in PC12 cells. Furthermore,
      vitexin treatment decreased the levels of isoflurane-induced cytosolic calcium
      and reactive oxygen species, and downregulated the expression of transient
      receptor potential cation channel subfamily V member 1 (TRPV1) and glutamate
      ionotropic receptor NMDA type subunit 2B (NR2B) protein expression in isoflurane
      treated PC12 cells. These results suggest that vitexin mediates its protective
      effects against isoflurane-induced neurotoxicity by targeting the TRPV1 and NR2B
      signaling pathways.

PMID- 27878304
TI  - Upregulation of MEK5 by Stat3 promotes breast cancer cell invasion and
      metastasis.
AB  - Mitogen extracellular-signal-regulated kinase kinase 5 (MEK5) plays an important
      role in promoting cell proliferation and tumorigenesis. The aberrant expression
      of MEK5 has been reported in various malignant diseases including cancers of
      breast, prostate, lung, colorectal and brain. However, the function and
      regulation of MEK5 signaling pathway are ambiguous and remain elusive with
      respect to its oncogenic roles in various cancers, especially in the regulation
      of the initiation and progression of cancer invasion and metastasis. Ectopic
      expression of MEK5 or knockdown of MEK5 by shRNA with in vitro cell based models
      demonstrated the role of MEK5 in regulation of epithelial mesenchymal transition
      (EMT) and breast cancer invasion and metastasis. Here, we show that MEK5
      upregulated by Stat3 promotes breast cancer cell invasion through EMT. Further
      study demonstrated that Stat3 could bind to promoter region of MEK5 and enhanced
      MEK5 transcription and expression. In addition, the phosphorylation of MEK5
      significantly increased in breast cancer cells corresponding to metastatic
      capability of breast cancer cells. The depletion of MEK5 by shRNA significantly
      decreased breast cancer invasion. Ectopic expression of MEK5 could confer non
      invasive breast cancer cells to become invasion capable cells. Moreover, the
      phosphorylation of Erk5, a MEK5-regulated downstream kinase, was also upregulated
      consistent with the increased level of active MEK5. Our studies provide insights
      into a molecular mechanism by which MEK5 transcriptionally upregulated by Stat3
      augments breast cancer cell EMT, which subsequently enhances cancer cell invasion
      and metastasis. This finding may suggest that Stat3 and MEK5/Erk5 pathways could
      be an effective therapeutic target for inhibition of breast cancer invasion and
      metastasis.

PMID- 27878305
TI  - miR-148a suppresses human renal cell carcinoma malignancy by targeting AKT2.
AB  - MicroRNA-148a (miR-148a) has been reported to be deregulated in different tumor
      types, whereas the biological function of miR-148a in renal cell carcinoma (RCC)
      largely remains unexplored. In the present study we investigated the clinical
      significance, biological effects, and the underlying molecular mechanisms of miR
      148 in RCC. Here, we showed that miR-148a was significantly downregulated in RCC
      tissues and cell lines. Low expression of miR-148a in RCC tissues was associated
      with large tumor size, advanced TNM stage, and lymph node metastasis. Functional
      assays revealed that overexpression of miR-148a significantly inhibited RCC cell
      proliferation, colony formation, migration and invasion in vitro and suppressed
      RCC xenograft tumor growth in vivo. In addition, using quantitative RT-PCR (qRT
      PCR), western blot analysis and luciferase reporter assays, AKT2 was confirmed to
      be a direct target of miR-148a. AKT2 expression was upregulated, and was
      negatively correlated with miR-148a expression in RCC tissues (r=-0.641,
      P<0.001). Silencing of AKT2 phenotypically copied miR-148a-induced phenotypes,
      whereas re-expression of AKT2 reversed the suppressive effects of miR-148a in RCC
      cells. Further mechanistic investigations showed that miR-148a exerted its
      antitumor activity via inhibition of the AKT pathway in vitro and in vivo. Taken
      together, these findings suggest that miR-148a functions as tumor suppressor in
      RCC by targeting AKT2.

PMID- 27878306
TI  - Effects of interleukin-1 receptor-associated kinase 1 RNA interference in
      dendritic cells on inflammatory cytokine release and T-cell proliferation.
AB  - The present study aimed to reduce the expression of interleukin-1 receptor
      associated kinase 1 (IRAK-1) in dendritic cells (DCs) by RNA interference (RNAi).
      Subsequently, its effects on the expression of costimulatory surface molecules,
      the release of inflammatory cytokines, and the proliferation of T cells during
      the activation process of DCs, were determined. RNAi was used to silence IRAK-1
      gene expression in DCs, followed by lipopolysaccharide stimulation. Flow
      cytometry was then used to detect the expression levels of DC surface molecules,
      including cluster of differentiation (CD)86, major histocompatibility complex
      class II and CD40. Quantitative polymerase chain reaction was conducted to detect
      the mRNA expression levels of Toll-like receptor 4, IRAK-4, IRAK-1 and nuclear
      factor-kappaB (NF-kappaB) in DCs. In addition, ELISA was used to detect the
      release of the following inflammatory cytokines: Interleukin (IL)-10, IL-12 and
      tumor necrosis factor-alpha (TNF-alpha). The MTS assay was used to determine the
      effects of IRAK-1 RNAi on T-cell proliferation. Knockdown of IRAK-1 gene
      expression in DCs significantly reduced the expression levels of costimulatory
      surface molecules and intracellular NF-kappaB, decreased release of the
      proinflammatory cytokines IL-12 and TNF-alpha, increased release of the anti
      inflammatory cytokine IL-10, and significantly reduced the proliferation of T
      cells. These results suggested that suppression of IRAK-1 gene expression may
      inhibit the differentiation and maturation of DCs via the downregulation of DC
      surface molecules, inhibition of intracellular signal transduction pathways,
      regulation of inflammatory cytokine release, and by reducing its promoting
      effects on T-cell proliferation.

PMID- 27878307
TI  - HMGA2 regulates epithelial-mesenchymal transition and the acquisition of tumor
      stem cell properties through TWIST1 in gastric cancer.
AB  - High expression of high mobility group protein A2 (HMGA2) is correlated with the
      invasiveness of gastric cancer and is an independent prognostic factor. The
      reason may be that HMGA2 promotes epithelial-mesenchymal transition (EMT) and the
      acquisition of tumor stem cell properties, yet the mechanism remains unclear. In
      this study, immunohistochemistry and western blot analysis revealed that the
      expression of HMGA2 and Twist-related protein 1 (TWIST1) in gastric carcinoma
      tissues was higher than that in the peritumoral tissues and that the expression
      levels of these two proteins were positively correlated. The protein expression
      levels of HMGA2 and TWIST1 were high in the poorly differentiated gastric cancer
      MKN-45 cells and were low in the moderately differentiated SGC-7901 cells. TWIST1
      was inhibited after HMGA2 interference and was significantly increased after
      overexpression of HMGA2. Luciferase experiments showed that TWIST1 was a direct
      downstream target gene of HMGA2. The simultaneous interference of HMGA2
      expression and the overexpression of TWIST1 in MKN-45 cells reversed the
      inhibitory effect of HMGA2 interference on the invasion and migration of gastric
      cancer cells, EMT and the expression of stemness markers. However, the
      simultaneous overexpression of HMGA2 and the interference of TWIST1 expression in
      the SGC-7901 cells reversed the promoter effect of HMGA2 overexpression on the
      invasiveness and migration of gastric cancer cells, EMT and the expression of
      stemness markers. In addition, animal experiments showed that TWIST1
      overexpression reversed the inhibition of HMGA2 interference on the metastasis of
      MKN-45 cells. Therefore, HMGA2 regulates the EMT of gastric cancer cells and the
      acquisition of tumor stem cell properties through direct regulation of the
      downstream target gene TWIST1.

PMID- 27878308
TI  - [Systemic lupus erythematosus : Unusual cutaneous manifestations].
AB  - BACKGROUND: Various different mucocutaneous symptoms may affect up to 80 % of
      systemic lupus erythematosus (SLE) patients. OBJECTIVES: To investigate, various
      unspecific, but otherwise typical clinical symptoms of skin and mucous membranes
      that arise in SLE patients other than those defined as SLE criteria such as
      butterfly rash, chronic cutaneous lupus erythematosus, oral ulcers, and increased
      photosensitivity. MATERIALS AND METHODS: Extensive search of peer-reviewed
      scientific articles was performed, medical histories of several SLE patients seen
      in our department were analyzed, and the rare disease courses in three SLE
      patients are presented. RESULTS: Here we present a variety of unspecific but
      typical mucocutaneous manifestations in SLE patients: periungual erythema,
      periungual telangiectasia and periungual splinter hemorrhage, papules on the
      dorsum of the hands, scaling erythema, sometimes associated with necrosis,
      especially of the ears, along with complement deficiency, and the bizarre
      necroses of antiphospholipid syndrome. Furthermore, we show the typical clinico
      histological features of neutrophilic urticarial dermatosis, as well as those of
      bullous SLE and finally a severe course of bacterial sepsis with Neisseria
      flavescens/macacae. CONCLUSIONS: Here we show several unspecific but rather
      typical mucocutaneous symptoms in lupus patients that are indicative of SLE and
      thus may lead to an early diagnosis. Also, life-threatening bacterial sepsis may
      occur with microorganisms that are commonly considered "apathogenic", such as
      Neisseria flavescens/macacae, which exclusively affect immunosuppressed patients.

PMID- 27878309
TI  - [Solitary node without symptoms on the cheek of a 3-year-old boy].

PMID- 27878310
TI  - Moving from vaginal hysterectomy to "no-incision" hysterectomy: how terminology
      has an impact.

PMID- 27878311
TI  - High-flow nasal cannula in hypoxemic patients: should I stay or should I go?

PMID- 27878312
TI  - Parental presence in Italian pediatric intensive care units: a reappraisal of
      current visiting policies.

PMID- 27878314
TI  - Erratum to: Novel diffusive gradients in thin films technique to assess labile
      sulfate in soil.

PMID- 27878315
TI  - A plasmonic ELISA for the naked-eye detection of chromium ions in water samples.
AB  - Here, we describe the development of a triangular silver nanoprism (AgNPR)
      etching-based plasmonic ELISA for the colorimetric determination of Cr(III)
      levels in environmental water samples. This involved the creation of a novel
      signal generation system (substrate reaction solution) for a competitive ELISA in
      which hydrogen peroxide (H2O2) is used to etch triangular AgNPRs, inducing a
      change in color. This is achieved by controlling the H2O2 concentration that
      remains after degradation by catalase, which is conjugated to the secondary
      antibody of the ELISA. Because the degree of color change and the shift in the
      absorption spectrum of the substrate reaction solution are closely correlated
      with the Cr(III) concentration, this plasmonic ELISA can be used not only for the
      quantification of Cr(III) concentrations ranging from 3.13 to 50 ng/mL, with a
      limit of detection (LOD) of 3.13 ng/mL, but also for the visual detection
      (indicated by a color change from blue to mauve) of Cr(III) with a sensitivity of
      6.25 ng/mL by the naked eye. Therefore, the plasmonic ELISA developed in this
      work represents a new strategy for heavy metal ion detection and has high
      potential applicability in resource-constrained areas. Graphical Abstract
      Schematic diagram of triangular silver nanoprism etching-based signal generation
      system.

PMID- 27878313
TI  - Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic
      effects of SGLT2 inhibition.
AB  - Healthy kidneys filter ~160 g/day of glucose (~30% of daily energy intake) under
      euglycaemic conditions. To prevent valuable energy from being lost in the urine,
      the proximal tubule avidly reabsorbs filtered glucose up to a limit of ~450
      g/day. When blood glucose levels increase to the point that the filtered load
      exceeds this limit, the surplus is excreted in the urine. Thus, the kidney
      provides a safety valve that can prevent extreme hyperglycaemia as long as
      glomerular filtration is maintained. Most of the capacity for renal glucose
      reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early
      proximal tubule. In the absence or with inhibition of SGLT2, the renal
      reabsorptive capacity for glucose declines to ~80 g/day (the residual capacity of
      SGLT1), i.e. the safety valve opens at a lower threshold, which makes it relevant
      to glucose homeostasis from day-to-day. Several SGLT2 inhibitors are now approved
      glucose lowering agents for individuals with type 2 diabetes and preserved kidney
      function. By inducing glucosuria, these drugs improve glycaemic control in all
      stages of type 2 diabetes, while their risk of causing hypoglycaemia is low
      because they naturally stop working when the filtered glucose load falls below
      ~80 g/day and they do not otherwise interfere with metabolic counterregulation.
      Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift
      substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies.
      Because SGLT2 reabsorbs sodium along with glucose, SGLT2 blockers are natriuretic
      and antihypertensive. Also, because they work in the proximal tubule, SGLT2
      inhibitors increase delivery of fluid and electrolytes to the macula densa,
      thereby activating tubuloglomerular feedback and increasing tubular back
      pressure. This mitigates glomerular hyperfiltration, reduces the kidney's demand
      for oxygen and lessens albuminuria. For reasons that are less well understood,
      SGLT2 inhibitors are also uricosuric. These pleiotropic effects of SGLT2
      inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME
      trial in which the SGLT2 inhibitor, empagliflozin, slowed the progression of
      chronic kidney disease and reduced major adverse cardiovascular events in high
      risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in
      the physiology and pathophysiology of renal glucose reabsorption and outlines the
      unexpected logic of inhibiting SGLT2 in the diabetic kidney.

PMID- 27878317
TI  - [What is currently available for sport medicine therapy?]
AB  - After 30 years of age physical capacity decreases with increasing age by 5-20%
      per decade. High physical activity in daily life as well as exercise training of
      endurance, strength, coordination and mobility can delay the functional and
      anatomical loss of muscle, bone, cartilage and connective tissue by more than 10
      years. In recent years, numerous concepts have scientifically been proven in the
      exercise therapy of internal diseases; therefore, similar to drug treatment,
      cellular mechanisms of exercise training adaptation are known in detail. With
      this knowledge the type, dose and intensity of exercise training can be defined
      in such a way that the targeted use of physical training can achieve health
      benefits similar to the effects achieved by drugs. This applies to the
      cardiovascular system, lungs, cancer, metabolic diseases and the immune system.
      In exercise training therapy of patients, individual exercise programs should be
      defined in a way that the contents of endurance, strength, coordination and
      mobility address all health and personal concerns of the patient. For sustained
      effects and high motivation, the individual and disease-specific definition of
      exercise programs as well as regular monitoring are necessary. The prescription
      for movement as well as the prescriptions for sports rehabilitation and
      functional training incorporate important assistance in this context.

PMID- 27878316
TI  - Impact of vitamin D replacement in adults and elderly in the Middle East and
      North Africa: a systematic review and meta-analysis of randomized controlled
      trials.
AB  - : In the Middle East and North Africa (MENA), a vitamin D dose >=2000 IU/day may
      be needed to allow to the majority of the population to reach the target 25
      hydroxyvitamin D (25(OH)D) level >=20 ng/ml. Data in the region on the effect of
      vitamin D supplementation on various skeletal and extra-skeletal effects are
      scarce. INTRODUCTION: Hypovitaminosis D is prevalent worldwide, more so in the
      Middle East and North Africa (MENA). This study aims to determine the effects of
      vitamin D replacement on the mean difference in 25-hydroxyvitamin D [25(OH)D]
      level reached and other outcomes, in the MENA. METHODS: This is a meta-analysis
      of randomized trials from the MENA, administering vitamin D supplementation for
      at least 3 months, without language or time restriction. We conducted a
      comprehensive search in seven databases until July 2015. We abstracted data from
      published reports, independently and in duplicate. We calculated the mean
      difference (MD) and 95 % CI of 25(OH)D level reached for eligible comparisons,
      and pooled data using RevMan version 5.3. RESULTS: We identified 2 studies in
      elderly and 17 in adults; for the latter, 11 were included in the meta-analysis.
      Comparing a high vitamin D dose (>2000 IU/day) to placebo (nine studies), the MD
      in 25(OH)D level achieved was 18.3 (CI 14.1; 22.5) ng/ml; p value < 0.001; I 2 =
      92 %. Comparing an intermediate dose (800-2000 IU/day) to placebo (two studies),
      the MD in 25(OH)D level achieved was 14.7 (CI 4.6; 24.9) ng/ml; p value 0.004; I
      2 = 91 %. Accordingly, 89 and 71 % of participants, in the high and intermediate
      dose groups, respectively, reached the desirable level of 20 ng/ml. The risk of
      bias in the included studies was unclear to high, except for three studies.
      CONCLUSION: In the MENA region, vitamin D doses >=2000 IU/day may be needed to
      reach the target 25(OH)D level >=20 ng/ml. The long-term safety and the efficacy
      of such doses on various outcomes are unknown.

PMID- 27878318
TI  - [Corticosteroids in the management of advanced prostate cancer].
AB  - Corticosteroids have been widely used for decades in cancer therapy,
      predominantly due to their anti-inflammatory activity. In the treatment of
      metastatic castration-resistant prostate cancer (mCRPC), corticosteroids play an
      important role both in the management of tumor-related symptoms, especially bone
      metastasis-related pain, and as concomitant treatment to counteract side effects
      associated with approved active prostatic anticancer agents such as docetaxel,
      cabazitaxel, and abiraterone acetate. In association with abiraterone acetate,
      low-dose corticosteroids (prednisone or prednisolone) reduce the
      mineralocorticoid side effects of abiraterone. In addition, corticosteroids may
      exert direct antitumoral activities, resulting in PSA decline.

PMID- 27878320
TI  - Geo-Accumulation Indices of Heavy Metals in Soil and Groundwater of Kanpur, India
      Under Long Term Irrigation of Tannery Effluent.
AB  - Soil and groundwater from long-term (>50 years) tannery effluent irrigated areas
      of Kanpur were analyzed and significant buildup of heavy metals such as Cr, Ni,
      Cd, Pb, Zn, and As in the range of 252-972, 23-30, 2.3-14.1, 23.7-58.8, 138-338
      and 6.8-11 mg kg-1, respectively in soil was found. Few groundwater samples in
      the effluent irrigated areas also exhibited high Cr concentration above the
      permissible limit of United States Environmental Protection Agency. The tannery
      effluents contained 1.53-57.3 ppm Cr, 0-0.12 ppm Ni, 0-0.02 ppm Cd, 0-0.07 ppm
      Pb, 0-0.48 ppm Zn and 0-0.03 ppm As. The Geo-accumulation index (Igeo) revealed
      that soil samples were unpolluted to moderately polluted with Cu, Ni, Zn, Pb and
      As; moderately polluted in case of Cd; and heavily to extremely polluted by Cr.

PMID- 27878319
TI  - Effects of Tetrabromobisphenol A Stress on Growth and Physiological
      Characteristics of Soybean Seedling.
AB  - The objective of this study was to investigate effects of tetrabromobisphenol A
      (TBBPA) on soybean seedlings. Growth and physiological parameters of soybean
      seedlings were measured by exposing seedlings to different concentrations of
      TBBPA (0, 5, 10, 20, 40, 80, and 100 mg kg-1 dry weight soil) in a greenhouse.
      Results showed 5 to 100 mg kg-1 TBBPA treatment reduced the shoot height, stem
      diameter, dry weight, and fresh weight, while 5 to 100 mg kg-1 TBBPA treatment
      reduced the chlorophyll content and induced production of malondialdehyde (MDA)
      in soybean leaves after 7 and 14 days of exposure. TBBPA treatment at low
      concentrations enhanced soluble sugar and soluble protein content, and it
      activated superoxide dismutase (SOD; EC:1.15.1.1), catalase (CAT; EC:1.11.1.6),
      and peroxidase (POD; EC:1.11.1.7); however, high concentrations of TBBPA
      inhibited activities of antioxidant enzymes and generation of soluble sugar and
      soluble protein.

PMID- 27878321
TI  - Do Varying Aquatic Plant Species Affect Phytoplankton and Crustacean Responses to
      a Nitrogen-Permethrin Mixture?
AB  - Hydraulically connected wetland microcosms vegetated with either Typha latifolia
      or Myriophyllum aquaticum were amended with an NH4NO3 and permethrin mixture to
      assess the effectiveness of both plant species in mitigating effects of the
      pollutant mixture on phytoplankton (as chlorophyll a) and Hyalella azteca.
      Phytoplankton grew in response to increased NH4NO3 in the presence of all plant
      species, but was unaffected by exposure to permethrin. H. azteca responses
      occurred rapidly (0.17 days), was mitigated within 1-2 days, and aqueous toxicity
      was unaffected by plant species type. A toxic unit model approach ascertained
      primary toxicity was permethrin with minimal additional toxicity from NH4NO3.
      Varying aquatic plant species had only modest influences on phytoplankton
      responses and no observable influence on animal responses during nitrogen
      permethrin mixture exposures. As a result, both T. latifolia and M. aquaticum can
      be used as part of an effective agricultural best-management practice system for
      mitigating pollutant impacts of agricultural run-off.

PMID- 27878322
TI  - Assessing needs for psychiatric treatment in prisoners: 1. Prevalence of
      disorder.
AB  - BACKGROUND: High levels of psychiatric morbidity in prisoners have important
      implications for services. Assessing Needs for Psychiatric Treatment in Prisoners
      is an evaluation of representative samples of prisoners in a male and a female
      prison in London. This paper reports on the prevalence of mental disorders. In a
      companion paper, we describe how this translates into mental health treatment
      needs and the extent to which they have been met. METHODS: Prisoners were
      randomly sampled in a sequential procedure based on the Local Inmate Data System.
      We interviewed roughly equal numbers from the following groups: male remand; male
      sentenced prisoners (Pentonville prison); and female remand; female sentenced
      prisoners (Holloway prison). Structured assessments were made of psychosis,
      common mental disorders, PTSD, personality disorder and substance abuse. RESULTS:
      We interviewed 197 male and 171 female prisoners. Psychiatric morbidity in male
      and female, sentenced and remand prisoners far exceeded in prevalence and
      severity than in equivalent general population surveys. In particular, 12% met
      criteria for psychosis; 53.8% for depressive disorders; 26.8% for anxiety
      disorders; 33.1% were dependent on alcohol and 57.1% on illegal drugs; 34.2% had
      some form of personality disorder; and 69.1% had two disorders or more. Moreover,
      in the year before imprisonment, 25.3% had used mental health services.
      CONCLUSIONS: These rates of mental ill-health and their similarity in remand and
      sentenced prisoners indicate that diversion of people with mental health problems
      from the prison arm of the criminal justice system remains inadequate, with
      serious consequences for well-being and recidivism.

PMID- 27878324
TI  - [The new DGUV requirements for treatment].

PMID- 27878323
TI  - Assessing needs for psychiatric treatment in prisoners: 2. Met and unmet need.
AB  - BACKGROUND: In a companion paper, we established high levels of psychiatric
      morbidity in prisoners (Bebbington et al. Soc Psychiatry Psychiatr Epidemiol,
      2016). In the current report, we evaluate how this morbidity translates into
      specific needs for treatment and the consequent implications for services. Mental
      health treatment needs and the extent to which they had been met were assessed in
      a representative sample of prisoners in a male and a female prison in London
      (Pentonville and Holloway). METHODS: Prisoners were sampled at random in a
      sequential procedure based on the Local Inmate Data System. We targeted equal
      numbers of male remand, male sentenced, female remand, and female sentenced
      prisoners. Following structured assessment of psychosis, common mental disorders,
      PTSD, personality disorders and disorders of abuse, we used the MRC Needs for
      Care Assessment (NFCAS) to establish whether potential needs for care in ten
      areas of mental health functioning were met, unmet, or incapable of being met by
      services. RESULTS: Data on treatment experience were provided by 360 inmates.
      Eighty percent of females and 70% of males had at least one need for treatment.
      Over half (53.7%) of the needs of female prisoners were met, but only one third
      (36.5%) in males. Needs for medication were unmet in 32% of cases, while those
      for psychological treatment were unmet in 51%. CONCLUSIONS: Unmet needs for
      mental health treatment and care were common in the two prisons. This has adverse
      consequences both for individual prisoners and for the effective functioning of
      the criminal justice system.

PMID- 27878325
TI  - ?

PMID- 27878327
TI  - ?

PMID- 27878326
TI  - A novel 72-kDa leukocyte-derived osteoglycin enhances the activation of toll-like
      receptor 4 and exacerbates cardiac inflammation during viral myocarditis.
AB  - BACKGROUND: Viral myocarditis can severely damage the myocardium through
      excessive infiltration of immune cells. Osteoglycin (OGN) is part of the small
      leucine-rich repeat proteoglycan (SLRP) family. SLRP's may affect inflammatory
      and fibrotic processes, but the implication of OGN in cardiac inflammation and
      the resulting injury upon viral myocarditis is unknown. METHODS AND RESULTS: This
      study uncovered a previously unidentified 72-kDa variant of OGN that is
      predominant in cardiac human and mouse samples of viral myocarditis. Its absence
      in mice significantly decreased cardiac inflammation and injury in Coxsackievirus
      B3-induced myocarditis. It also delayed mortality in lipopolysaccharide-induced
      endotoxemia going along with a reduced systemic production of pro-inflammatory
      cytokines. This 72-kDa OGN is expressed in the cell membrane of circulating and
      resident cardiac macrophages and neutrophils. Co-immunoprecipitation and OGN
      siRNA experiments revealed that this 72-kDa variant activates the toll-like
      receptor-4 (TLR4) with a concomitant increase in IL-6, TNF-alpha, IL-1beta, and
      IL-12 expression. This immune cell activation by OGN occurred via MyD88 and
      increased phosphorylation of c-jun. Finally, the 72-kDa chondroitin sulfate is
      the result of O-linked glycosylation of the 32-kDa protein core of OGN. In
      contrast, the 34-kDa dermatan sulfate-OGN, involved in collagen cross linking,
      was also the result of O-linked glycosylation. CONCLUSION: The current study
      discovered a novel 72-kDa chondroitin sulfate-OGN that is specific for innate
      immune cells. This variant is able to bind and activate TLR4. The absence of OGN
      decreases cytokine production by both circulating and cardiac leukocytes upon
      (systemic) LPS exposure, and reduces cardiac inflammation and injury in viral
      myocarditis.

PMID- 27878328
TI  - Targeting the hedgehog signaling pathway for cardiac repair and regeneration.
AB  - The hedgehog (Hh) signaling pathway is involved in the angiogenesis and
      development of the coronary vasculature in the embryonic heart. Recently, the Hh
      signal pathway has emerged as an important regulator that can increase
      cardiomyocyte proliferation, inhibit cardiomyocyte death and apoptosis, recruit
      endothelial progenitor cell (EPCs) into sites of myocardial ischemia, and direct
      stem cells to differentiate into cardiac muscle lineage. Experimental studies
      have tried to target the Hh signaling pathway for cardiac repair and
      regeneration. The purpose of this review is to discuss the role of the Hh signal
      pathway in cardiac repair and regeneration as well as the current strategies
      targeting the Hh signaling pathway and its potential in heart diseases.

PMID- 27878330
TI  - [Volunteering in end-of-life care : Challenges, problems and perspectives].
AB  - Volunteering in the hospice movement has had a profound impact on generating
      awareness of hospice work and palliative care in the context of supporting dying
      persons and their relatives as well as on integrating respective services in the
      existing health care system. This paper focuses on two specific questions: First,
      it asks how society is changing with respect to dealing with dying and death, and
      more precisely with dying persons, which is recognizable by the integration of
      hospice work and palliative care in the healthcare system and related to the
      relevance of volunteering in the sense of a citizens' movement. Second, this
      paper asks what the specific roles of volunteers are as well as the possibilities
      and limits of voluntary practice in end-of-life care and accompaniment. To answer
      these questions, the pivotal objectives of the hospice movement - the
      transformation of the social awareness regarding dying and death, as well as the
      reorganization of "institutions of dying" - will first be outlined by reference
      to the concept of "good dying", a specific hospice attitude together with hospice
      culture and palliative competence. In a second step, the relevance of
      volunteering and the specific role of volunteers in the actual practice of
      hospice work and palliative care will be outlined alongside current indicators
      and recognizable alteration tendencies, before concluding with a discussion of
      the perspectives of hospices as a citizens' movement.

PMID- 27878329
TI  - The role of regulatory B cells in digestive system diseases.
AB  - INTRODUCTION: The past decade has provided striking insights into a newly
      identified subset of B cells known as regulatory B cells (Bregs). In addition to
      producing antibody, Bregs also regulate diseases via cytokine production and
      antigen presentation. This subset of B cells has protective and potentially
      therapeutic effects. However, the particularity of Bregs has caused some
      difficulties in conducting research on their roles. Notably, human B10 cells,
      which are Bregs that produce interleukin 10, share phenotypic characteristics
      with other previously defined B cell subsets, and currently, there is no known
      surface phenotype that is unique to B10 cells. METHODS: An online search was
      performed in the PubMed and Web of Science databases for articles published
      providing evidences on the role of regulatory B cells in digestive system
      diseases. RESULTS AND CONCLUSIONS: Abundant evidence has demonstrated that Bregs
      play a regulatory role in inflammatory, autoimmune, and tumor diseases, and
      regulatory B cells play different roles in different diseases, but future work
      needs to determine the mechanisms by which Bregs are activated and how these
      cells affect their target cells.

PMID- 27878331
TI  - Fluoroscopy versus ultrasound for image guidance during percutaneous
      nephrolithotomy: a systematic review and meta-analysis.
AB  - This meta-analysis aims to compare the safety and efficacy of fluoroscopy versus
      ultrasound guidance during the access to the renal collecting system. A
      systematic literature review was performed in September 2016. Outcomes were
      explored using review manager v5.0. 18 studies with 2919 patients were included
      in the final analysis. There was no significant difference in stone-free rate
      (RR: 1.0; 95% CI, 0.98 to 1.05; p = 0.41), operation time (MD: 1.75; 95% CI, 
      9.15 to 12.65; p = 0.75), hospital stay (MD: -1.02; 95% CI, -3.08 to 1.05; p =
      0.34), and success rate of tract creation (RR: 1.00; 95% CI, 0.98-1.02; p = 0.88)
      between ultrasonography and fluoroscopy. Compared to fluoroscopy, ultrasonography
      had shorter puncture time (MD: -4.71; 95% CI, -6.43 to -3.0; p < 0.0001), higher
      success rate of fist puncture (RR: 1.16; 95% CI, 1.04 to 1.3; p = 0.01), less
      blood loss (MD: -0.42, 95% CI -0.81 to -0.02; p = 0.04), and less transfusion
      requirement (RR: 0.73; 95% CI, 0.33-1.6; p = 0.44). Two patients in each group
      experienced perforation of the renal pelvis. Five patients in fluoroscopy and two
      in ultrasonography group had pneumothorax. One patient in fluoroscopy group had
      intestinal injury. Both fluoroscopy and ultrasound guidance can aid to obtain
      successful percutaneous renal access. The advantages of ultrasonography over
      fluoroscopy include shorter puncture time, higher success rate of fist puncture,
      less blood loss, and less complications.

PMID- 27878332
TI  - Accelerated Cardiac Rhabdomyoma Regression with Everolimus in Infants with
      Tuberous Sclerosis Complex.
AB  - Tuberous sclerosis complex is associated with benign tumors such as cardiac
      rhabdomyomas (RHM) caused by the disinhibition of the mammalian target of
      rapamycin (mTOR) protein. Recent reports on everolimus, an mTOR inhibitor, have
      shown size reduction of RHM. We compared cases recently treated with everolimus
      to historic controls whose first echocardiography was within first month of life.
      The largest dimension of the largest RHM was reported as a percentage compared to
      the earliest echocardiography study. Treatment of the four cases was started at a
      median age of 6.5 days (range 2-20) with an initial enteral dose of 0.1 mg daily,
      aiming at a therapeutic serum trough level of 5-15 ng/mL. Median duration of
      everolimus treatment was 73 days (range 34-138). Compared to 10 historic
      controls, everolimus-treated patients had 11.8 times faster RHM size regression
      rate (slope -0.0285 vs. -0.0024; p < 0.001). The average time to 50% size
      reduction was 1.13 +/- 0.33 month (range 0.66-1.4 months) with everolimus versus
      72.9 +/- 53.03 months in controls (p = 0.026). Following treatment with
      everolimus, one case was operated for congenital heart disease, without
      requirement of RHM resection, two others had the massive left ventricle RHM
      shrink to non-consequential size. The latter had a disappearance of RHM, but
      everolimus therapy was maintained to prevent the regrowth of a significant
      cerebral tumor. Everolimus is efficacious for size reduction of RHM during the
      neonatal period. With limited safety data, this approach should be used with
      caution in selective cases.

PMID- 27878333
TI  - Transcatheter Pulmonary Valve Replacement and Acute Increase in Diastolic
      Pressure are Associated with Increases in Both Systolic and Diastolic Pulmonary
      Artery Dimensions.
AB  - Stable positioning of a transcatheter pulmonary valve (TPV) in native outflow
      tracts depends on a clear understanding of underlying anatomy and outflow tract
      dimensions. We hypothesized that restoration of pulmonary competence may acutely
      alter these dimensions. A retrospective single-center review of consecutive
      patients after TPV placement from 2007 to 2014 was performed. Patients with less
      than moderate pulmonary regurgitation were excluded. We reviewed acute
      catheterization data on 46 patients, most with tetralogy of Fallot (70%).
      Baseline and post-implant (7.5 +/- 3 min post-deployment) measurements of central
      pulmonary arteries (PAs) were determined angiographically. The right PA diameter
      increased (20 +/- 4-24 +/- 6 mm systole*, 16 +/- 4-21 +/- 6 mm diastole*), as did
      the left PA (20 +/- 6-24 +/- 8 mm systole*, 16 +/- 5-21 +/- 7 mm diastole*). PA
      pressures increased from averages of 29.3/10.6 (17) to 29.8/15.1 (21) mmHg. We
      noted that pre-implant systolic PA diameter correlated with diastolic PA diameter
      post-implant (r = 0.9). On follow-up catheterization in seven patients [median 3
      years; (1-8)], combined central PA diameter decreased an average of 20% (systole:
      20% +/- 12, diastole: 18% +/- 11) as compared to post-implant measurements. Acute
      pulmonary valve competence in patients with at least moderate pulmonary
      regurgitation results in an immediate increase in PA diameter (20% systole and
      30% diastole). The cause of this diameter change is unclear. This acute change
      may have implications for device and patient selection (*p < 0.001).

PMID- 27878334
TI  - Equivalent wear performance of dual mobility bearing compared with standard
      bearing in total hip arthroplasty: in vitro study.
AB  - PURPOSE: Osteolysis in total hip arthroplasty (THA) depends on polyethylene wear
      and dictates the survival of the prosthesis. Dual mobility in THAs, which is
      claimed to reduce dislocation risk, has very good long-term clinical results.
      However, little is known about how the liner wears in this design, compared to
      the standard single mobility model. METHODS: A comparative study looking at wear
      of a conventional ultra-high-molecular-weight polyethylene liner, using
      gravimetric measurement, between dual mobility implants and standard implants,
      was performed on a simulator in accordance with a normed protocol based on the
      same dimensions, environmental conditions and stresses. A linear regression test
      was employed. RESULTS: Under the same conditions (loading, cycles, sterilization,
      material and surface roughness), the gravimetric wear (for conventional
      polyethylene) is comparable between a standard and a dual mobility cup. This
      correlates to ten year follow-up results of dual mobility cup. DISCUSSION -
      CONCLUSION: This in vitro equivalent wear serves to confirm the very good long
      term clinical results observed with dual mobility bearing, whose use should not
      be restricted by concerns about increased polyethylene wear.

PMID- 27878335
TI  - Soil-covered strategy for ecological restoration alters the bacterial community
      structure and predictive energy metabolic functions in mine tailings profiles.
AB  - Native soil amendment has been widely used to stabilize mine tailings and speed
      up the development of soil biogeochemical functions before revegetation; however,
      it remains poorly understood about the response of microbial communities to
      ecological restoration of mine tailings with soil-covered strategy. In this
      study, microbial communities along a 60-cm profile were investigated in mine
      tailings during ecological restoration of two revegetation strategies (directly
      revegetation and native soil covered) with different plant species. The mine
      tailings were covered by native soils as thick as 40 cm for more than 10 years,
      and the total nitrogen, total organic carbon, water content, and heavy metal (Fe,
      Cu, and Zn) contents in the 0-40 cm intervals of profiles were changed. In
      addition, increased microbial diversity and changed microbial community structure
      were also found in the 10-40 cm intervals of profiles in soil-covered area. Soil
      covered strategy rather than plant species and soil depth was the main factor
      influencing the bacterial community, which explained the largest portion (29.96%)
      of the observed variation. Compared directly to revegetation, soil-covered
      strategy exhibited the higher relative abundance of Acidobacteria and
      Deltaproteobacteria and the lower relative abundance of Bacteroidetes,
      Gemmatimonadetes, Betaproteobacteria, and Gammaproteobacteria. PICRUSt analysis
      further demonstrated that soil-covered caused energy metabolic functional changes
      in carbon, nitrogen, and sulfur metabolism. Given all these, the soil-covered
      strategy may be used to fast-track the establishment of native microbial
      communities and is conducive to the rehabilitation of biogeochemical processes
      for establishing native plant species.

PMID- 27878336
TI  - Co-culturing Effects of Coexisting Bacteria on Wood Degradation by Trametes
      versicolor.
AB  - White-rot fungi are the main decomposers of wood cell-wall polymer in forest
      ecosystems. Little is known, however, about the interactions between white-rot
      fungi and other coexisting microorganisms in decayed wood. A white-rot fungus,
      Trametes versicolor strain TN6F, was isolated from a fruit body, and 44 strains
      of coexisting cultivable bacteria were isolated from its substrate, natural white
      rot-decayed wood. The effects of these bacteria on fungal growth were examined by
      an in vitro confrontation growth assay. Among the isolates, nine bacterial
      strains inhibited the growth of strain TN6F, while 35 strains did not affect the
      growth of TN6F. However, when co-cultured with strain TN6F on wood powder, many
      bacterial strains promoted the weight loss of the substrate. A subsequent
      chemical composition analysis showed that co-culturing accelerated
      delignification. Higher laccase activity was detected when strain TN6F was co
      cultured on wood powder medium with bacterial strains TN6W-26 or TN6W-27. These
      results indicate that some bacterial strains might promote wood degradation.

PMID- 27878337
TI  - Classics in abdominal imaging: the dependent viscera sign.

PMID- 27878338
TI  - Reporting standards for the imaging-based diagnosis of renal masses on CT and
      MRI: a national survey of academic abdominal radiologists and urologists.
AB  - PURPOSE: To define important elements of a structured radiology report of a CT or
      MRI performed to evaluate an indeterminate renal mass. METHODS: IRB approval was
      waived for this multi-site prospective quality improvement study. A 35-question
      survey investigating elements of a CT or MRI report describing a renal mass was
      created through an iterative process by the Society of Abdominal Radiology
      Disease-Focused Panel on renal cell carcinoma. Surveys were distributed to
      consenting abdominal radiologists and urologists at nine academic institutions.
      Consensus within and between specialties was defined as >=70% agreement.
      Respondent rates were compared with Chi Square test. RESULTS: The response rate
      was 68% (117/171; 55% [39/71] urologists, 78% [78/100] radiologists). Inter
      specialty consensus was that the following were essential: mass size with
      comparison to prior imaging, mass type (cystic vs. solid), presence of fat,
      presence of enhancement, and radiologic stage. Urologists were more likely to
      prefer the Nephrometry score (75% [27/36] vs. 22% [17/76], p < 0.0001),
      quantitative reporting of enhancement on CT (85% [32/38] vs. 46% [36/77], p <
      0.0001), and mass position with respect to the renal polar lines (67% [24/36] vs.
      36% [27/76], p = 0.002). There was inter-specialty consensus that the Bosniak
      classification for cystic masses was preferred. Most urologists (60% [21/35])
      preferred management recommendations be omitted for solid masses or Bosniak III
      IV cystic masses. CONCLUSIONS: Important elements to include in a CT or MRI
      report of an indeterminate renal mass are critical diagnostic features, the
      Bosniak classification if relevant, and the most likely specific diagnosis when
      feasible; including management recommendations is controversial.

PMID- 27878339
TI  - Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome.
AB  - Noonan syndrome is a genetic disorder with variable expression of distinctive
      facial features, webbed neck, chest deformity, short stature, cryptorchidism and
      congenital heart disease. The association of Noonan syndrome and giant cell
      granulomas of the mandible is widely reported. However, Noonan syndrome may also
      be associated with single or multifocal tenosynovial giant cell tumors, also
      referred to as pigmented villonodular synovitis. We report a child with Noonan
      syndrome, giant cell granulomas of the mandible and synovial and tenosynovial
      giant cell tumors involving multiple joints and tendon sheaths who was initially
      misdiagnosed with juvenile idiopathic arthritis. It is important for radiologists
      to be aware of the association of Noonan syndrome and multifocal giant cell
      lesions, which can range from the more commonly described giant cell granulomas
      of the mandible to isolated or multifocal intra- or extra-articular tenosynovial
      giant cell tumors or a combination of all of these lesions.

PMID- 27878340
TI  - Anatomical risk evaluation of iatrogenic injury to the infrapatellar branch of
      the saphenous nerve during medial meniscus arthroscopic surgery.
AB  - PURPOSE: To determine the relationship of the medial meniscus with the
      infrapatellar branches of the saphenous nerve, the primary goal is to define and
      characterize different risk areas for these nerves during medial meniscus
      surgery. METHODS: After dissecting 20 embalmed cadaver knees, we defined 7
      readily identifiable anatomical landmarks. For each knee, we recorded 2
      morphological criteria and 16 measurements. RESULTS: The most common anatomical
      course is a main trunk that is 8 mm anterior to the tuberculum adductorium and 60
      mm posterior to the midpoint of the medial patellar margin. It has two main
      infrapatellar branches. The nerve division is 23 mm above the joint line. The
      path is oblique with an angle of 55.5 degrees . The anterior meniscal landmark is
      24 mm from the upper branch and 42.5 mm from the lower branch. The posterior
      meniscal landmark is 55 mm from the upper branch and 38 mm from the lower branch.
      CONCLUSIONS: We defined a common anatomical course for the saphenous nerve and
      its infrapatellar branches. Then, three different areas were defined at risk for
      iatrogenic nerve injuries during medial meniscus.

PMID- 27878341
TI  - Initiation of forward gait with lateral occurrence of emotional stimuli: general
      findings and relevance for pedestrians crossing roads.
AB  - With reference to theoretical models regarding links between emotions and
      actions, the present study examined whether the lateral occurrence of an
      emotional stimulus influences spatial and temporal parameters of gait initiation
      in 18 younger and 18 older healthy adults. In order to simulate road-crossing
      hazard for pedestrians, slides of approaching cars were used and they were
      presented in counterbalanced order with threatening slides from the International
      Affective Picture System (IAPS) and control slides of safe walking areas. Each
      slide was presented on the left side of the participant once the first step was
      initiated. The results evidenced medio-lateral shifts to the left for the first
      step (right foot) and to the right for the second step (left foot). These shifts
      were both modulated by the slide contents in such a way that the resulting
      distance between the screen and the foot (right or left) was larger with the IAPS
      and traffic slides than with the control slides. The slides did not affect the
      base of support, step length, step velocity and time of double support. Advancing
      age influenced the subjective impact of the slides and gait characteristics, but
      did not modulate medio-lateral shifts. The data extend evidence of fast,
      emotional modulation of stepping, with theoretical and applied consequences.

PMID- 27878343
TI  - 30-Day, 90-day and 1-year mortality after emergency colonic surgery.
AB  - PURPOSE: Emergency surgery is an independent risk factor in colonic surgery
      resulting in high 30-day mortality. The primary aim of this study was to report
      30-day, 90-day and 1-year mortality rates after emergency colonic surgery, and to
      report factors associated with 30-day, 90-day and 1-year mortality. Second, the
      aim was to report 30-day postoperative complications and their relation to in
      hospital mortality. METHODS: All patients undergoing acute colonic surgery in the
      period from May 2009 to April 2013 at Copenhagen University Hospital Herlev,
      Denmark, were identified. Perioperative data was collected from medical journals.
      RESULTS: 30-day, 90-day and 1-year mortality was 21, 30 and 41%, respectively.
      Age >70 years, Performance status >=3 and resection with stoma were independent
      factors associated with 30-day mortality. Age >70 years, Performance status >=3,
      resection with stoma and malignant disease were independent risk factors
      associated with 90-day mortality. Age >70 years, Performance status >=3,
      resection with stoma and malignant disease were independent factors associated
      with 1-year mortality. Overall, 30-day complication rate was 63%, with
      cardiopulmonary complications leading to most postoperative deaths. CONCLUSION:
      Mortality and complication rates after emergency colonic surgery are high and
      associated with patient related risk factors that cannot be modified, but also
      treatment related outcomes that are modifiable. An increased focus on medical and
      other preventive measures should be explored in the future.

PMID- 27878345
TI  - Low vaccination rates among patients with rheumatoid arthritis in a German
      outpatient clinic.
AB  - Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring
      infections due to two reasons: the disease itself and the immunosuppressive
      therapy. Vaccinations against preventable diseases are therefore of utmost
      importance for these group of patients. To estimate vaccination frequencies among
      patients with rheumatoid arthritis, we studied patients in a survey and
      calculated vaccination rates based on their vaccination documents. Patients have
      been recruited from our outpatient clinic during one of their routine visits. For
      the statistical analysis, they have been divided by age (>=60 vs <60 years) and
      medication (DMARD, Biologics, TNF inhibitors) for further subgroup analysis.
      Among the studied patients (n = 331), we found rather low vaccination rates, in
      particular for the strongly recommended vaccines against Pneumococcus and
      Influenza (33 and 53%, respectively). Furthermore, protection rates for important
      basic vaccinations, e.g. against Pertussis, were found to be very low with 12%
      only. Beside these findings, we saw age-dependent differences for a variety of
      vaccines: while Pneumococcus and Influenza vaccines were more often given to
      patients >=60 years, MMR, Pertussis, Diphtheria and Hepatitis were significantly
      more often applied to younger patients. Vaccination rates have to be improved
      among RA patients, in particular for vaccines protecting from respiratory tract
      infections such as Pneumococcus.

PMID- 27878344
TI  - Comparison of soluble urokinase plasminogen activator receptor, soluble
      triggering receptor expressed on myeloid cells 1, procalcitonin and C-reactive
      protein in distinguishing concurrent bacterial infection from idiopathic
      inflammatory myopathy.
AB  - The aim of the study was to measure the diagnostic values of biomarkers of
      bacterial infection in idiopathic inflammatory myopathy (IIM) patients. The serum
      and clinical data of 82 IIM patients with/without bacterial infection were
      collected. Concentrations of soluble urokinase plasminogen activator receptor
      (suPAR), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1),
      procalcitonin (PCT) and C-reactive protein (CRP) were measured in IIM patients
      and healthy controls. There were no significant differences in serum suPAR and
      sTREM-1 levels between healthy controls and non-infection IIM patients. Serum
      levels of suPAR, sTREM-1, PCT and CRP measured in this study were significantly
      higher in the IIM patient group with concurrent infection than in the non
      infection IIM patient group (p < 0.05). The biomarker suPAR showed the highest
      diagnostic value with sensitivity, specificity, positive predictive value and
      negative predictive value of 81.6, 77.3, 75.6 and 82.9%, respectively. Combining
      suPAR negative and CRP negative to rule out bacterial infection in IIM patients
      provides a very high specificity of 97.4%. Both suPAR and CRP positive to confirm
      bacterial infection give the specificity of 90.9%. The inflammatory biomarkers
      suPAR, sTREM-1, PCT and CRP offer diagnostic accuracy in detecting bacterial
      infection in IIM patients. Particularly, suPAR is the most sensitive and specific
      biomarker to predict bacterial infection in IIM patients. Combination of suPAR
      and CRP serum levels provides an even better confirmation of bacterial infection.

PMID- 27878346
TI  - Salinity Affects the Composition of the Aerobic Methanotroph Community in
      Alkaline Lake Sediments from the Tibetan Plateau.
AB  - Lakes are widely distributed on the Tibetan Plateau, which plays an important
      role in natural methane emission. Aerobic methanotrophs in lake sediments reduce
      the amount of methane released into the atmosphere. However, no study to date has
      analyzed the methanotroph community composition and their driving factors in
      sediments of these high-altitude lakes (>4000 m). To provide new insights on this
      aspect, the abundance and composition in the sediments of six high-altitude
      alkaline lakes (including both freshwater and saline lakes) on the Tibetan
      Plateau were studied. The quantitative PCR, terminal restriction fragment length
      polymorphism, and 454-pyrosequencing methods were used to target the pmoA genes.
      The pmoA gene copies ranged 104-106 per gram fresh sediment. Type I methanotrophs
      predominated in Tibetan lake sediments, with Methylobacter and uncultivated type
      Ib methanotrophs being dominant in freshwater lakes and Methylomicrobium in
      saline lakes. Combining the pmoA-pyrosequencing data from Tibetan lakes with
      other published pmoA-sequencing data from lake sediments of other regions, a
      significant salinity and alkalinity effect (P = 0.001) was detected, especially
      salinity, which explained ~25% of methanotroph community variability. The main
      effect was Methylomicrobium being dominant (up to 100%) in saline lakes only. In
      freshwater lakes, however, methanotroph composition was relatively diverse,
      including Methylobacter, Methylocystis, and uncultured type Ib clusters. This
      study provides the first methanotroph data for high-altitude lake sediments
      (>4000 m) and shows that salinity is a driving factor for the community
      composition of aerobic methanotrophs.

PMID- 27878348
TI  - Erratum to: Prognostic Relevance of the Timing of Initiating and the Completion
      of Adjuvant Therapy in Patients with Resected Pancreatic Ductal Adenocarcinoma.

PMID- 27878349
TI  - Operation Start Times and Postoperative Morbidity from Liver Resection: A
      Propensity Score Matching Analysis.
AB  - BACKGROUND: Surgeons are likely to get progressively fatigued and work less
      effectively during the course of a normal workday. We sought to examine the
      effects of surgery start times (morning vs. afternoon) and workload of the
      surgeons on morbidity of patients after partial liver resection (LR). METHODS: A
      total of 155 pairs of the patients from 383 patients undergoing LR were generated
      by propensity score analysis (PSM) according to the start times of surgery: group
      M (morning surgery, 8 a.m.-1 p.m.) and group A (afternoon surgery, 1 p.m.-6
      p.m.). Patients in group A were further divided depending on whether or not the
      surgeons had performed other surgeries earlier in the day and the exact duration
      of the other surgeries before the afternoon surgery (<=180 and >180 min). The
      incidence and severity of postoperative complications were compared between
      different groups. RESULTS: By using PSM analysis, the patients in group M and
      group A were well matched in basic characteristics. The incidence and severity of
      the postoperative complications were similar between the two groups (all p >
      0.05). Whether the surgeons had performed other surgeries prior to the afternoon
      surgery seemed not affecting the postoperative outcome (all p > 0.05). Moreover,
      the duration of other surgeries the surgeons had performed did not have
      significant influence on the outcome of patients undergoing afternoon surgery
      (all p > 0.05). CONCLUSIONS: Surgery start times and workload of surgeons during
      working time did not measurably affect short-term outcomes of the patients. The
      negative findings might be a manifestation of professional judgment and self
      regulation of the experienced physicians.

PMID- 27878347
TI  - Detection and Diversity of the Nitrite Oxidoreductase Alpha Subunit (nxrA) Gene
      of Nitrospina in Marine Sediments.
AB  - Nitrite-oxidizing bacteria (NOB) are chemolithoautotrophs that catalyze the
      oxidation of nitrite to nitrate, which is the second step of aerobic
      nitrification. In marine ecosystems, Nitrospina is assumed to be a major
      contributor to nitrification. To date, two strains of Nitrospina have been
      isolated from marine environments. Despite their ecological relevance, their
      ecophysiology and environmental distribution are understudied owing to fastidious
      cultivation techniques and the lack of a sufficient functional gene marker. To
      estimate the abundance, diversity, and distribution of Nitrospina in various
      marine sediments, we used nxrA, which encodes the alpha subunit of nitrite
      oxidoreductase, as a functional and phylogenetic marker. We observed that
      Nitrospina diversity in polar sediments was significantly lower than that of non
      polar samples. Moreover, nxrA-like sequences revealed an unexpected diversity of
      Nitrospina, with approximately 41,000 different sequences based on a 95%
      similarity cutoff from six marine sediments. We detected nxrA gene copy numbers
      of up to 3.57 * 104 per gram of marine sediment sample. The results of this study
      provide insight into the distribution and diversity of Nitrospina, which is
      fundamentally important for understanding their contribution to the nitrogen
      cycle in marine sediments.

PMID- 27878342
TI  - Breeding approaches and genomics technologies to increase crop yield under low
      temperature stress.
AB  - KEY MESSAGE: Improved knowledge about plant cold stress tolerance offered by
      modern omics technologies will greatly inform future crop improvement strategies
      that aim to breed cultivars yielding substantially high under low-temperature
      conditions. Alarmingly rising temperature extremities present a substantial
      impediment to the projected target of 70% more food production by 2050. Low
      temperature (LT) stress severely constrains crop production worldwide, thereby
      demanding an urgent yet sustainable solution. Considerable research progress has
      been achieved on this front. Here, we review the crucial cellular and metabolic
      alterations in plants that follow LT stress along with the signal transduction
      and the regulatory network describing the plant cold tolerance. The significance
      of plant genetic resources to expand the genetic base of breeding programmes with
      regard to cold tolerance is highlighted. Also, the genetic architecture of cold
      tolerance trait as elucidated by conventional QTL mapping and genome-wide
      association mapping is described. Further, global expression profiling techniques
      including RNA-Seq along with diverse omics platforms are briefly discussed to
      better understand the underlying mechanism and prioritize the candidate gene (s)
      for downstream applications. These latest additions to breeders' toolbox hold
      immense potential to support plant breeding schemes that seek development of LT
      tolerant cultivars. High-yielding cultivars endowed with greater cold tolerance
      are urgently required to sustain the crop yield under conditions severely
      challenged by low-temperature.

PMID- 27878350
TI  - Home Return After Surgery in Patients Aged over 85 Years is Associated with
      Preoperative Albumin Levels, the Type of Surgery, and APACHE II Score.
AB  - BACKGROUND: Owing to an aging society, both the number of operations for patients
      aged >85 years and the average age of patients admitted to the intensive care
      unit (ICU) are rapidly increasing. However, mortality is not an appropriate
      outcome measurement in patients aged >85 years; a more important outcome is home
      return (HR), because quality of life is valuable to these patients. We identified
      predictors for HR of patients aged >85 years admitted to the ICU after surgery.
      METHODS: Retrospective analysis of medical records was conducted at a university
      hospital. Patients aged > 85 years, admitted to the ICU after surgery from March
      2006 to June 2015 (n = 187), were divided into a HR group (patients who returned
      home after discharge) and non-HR group (deceased or transferred to nursing
      facilities). Perioperative data and outcome were assessed and compared.
      Multivariate logistic regression analysis was conducted to identify independent
      predictors. RESULTS: The average age of patients was 88 years. HR occurred in 61%
      of patients, and mortality was 9%. The HR group had higher preoperative albumin
      level than did the non-HR group. More patients in the non-HR group experienced
      hip surgery than in the HR group (51 vs. 12%, P < 0.001). APACHE II score was
      higher (P < 0.001) in the non-HR group. In multivariate analysis, preoperative
      albumin, hip surgery, and APACHE II score were independent predictors of HR.
      CONCLUSION: Predictors of HR of surgical critically ill elderly patients included
      preoperative albumin level, hip surgery, and APACHE II score on ICU admission.

PMID- 27878352
TI  - Perioperative Risks of Dietary and Herbal Supplements.
AB  - BACKGROUND: Patients undergoing surgery often use Dietary and Herbal Supplements
      (DHS). We explored the risk of DHS-drug interactions in the perioperative
      setting. METHODS: In this cross-sectional prospective study, participants
      hospitalized for surgery completed a questionnaire regarding DHS use. We used
      pharmacological databases to assess DHS-drug interactions. We then applied
      univariate and multivariate logistic regression analyses to characterize patients
      at risk for DHS-drug interactions. RESULTS: Of 526 interviewees, 230 (44%)
      patients reported DHS use, with 16.5% reporting using DHS that could potentially
      interact with anesthesia. Twenty-four (10%) patients used DHS that could
      potentially interact with antithrombotic drugs taken perioperatively. The medical
      files of three patients included reports of intraoperative bleeding. The patient
      files of only 11% of DHS users documented DHS use. CONCLUSIONS: DHS use poses a
      significant health risk due to potential interactions. Guidelines should
      emphasize perioperative management of DHS use.

PMID- 27878351
TI  - C-Reactive Protein Indicates Early Stage of Postoperative Infectious
      Complications in Patients Following Minimally Invasive Esophagectomy.
AB  - BACKGROUND: Esophagectomy for patients with esophageal cancer is associated with
      high rate of postoperative infectious complications (PICs). Although minimally
      invasive esophagectomy (MIE) could reduce the rate of PICs, its incidence cannot
      be ignored. Early detection of PICs may be beneficial in clinical settings. We
      investigated whether systemic inflammation markers, such as C-reactive protein
      (CRP) and white blood cell count (WBC), are useful for the early detection of
      PICs. METHOD: We reviewed 158 patients who underwent MIE from 2000 to 2015 and
      assessed PIC incidence and severity. The value of CRP and WBC in the early
      detection of PICs was evaluated by receiver operating characteristics analyses.
      Univariate and multivariate analyses were performed to identify severe PICs risk
      factors (Clavien-Dindo classification, grade IIIa or higher). RESULTS: Thirty
      patients developed PICs: grades III, IV, and V in 19 (12.0%), 9 (5.7%), and 2
      (1.3%) patients, respectively. CRP on 4POD showed the highest value for detection
      of PICs (AUC = 072). Cutoff value of CRP on 4POD was determined as 11.1 (mg/dL),
      in which the sensitivity and specificity were the maximum value. The univariate
      analysis revealed that sex (male), operation time (>=597 min), and CRP on 4POD
      (>=11.1 mg/dL) were significant factors for detecting PICs. Multivariate analyses
      showed that operation time (>=597) and CRP on 4POD (>=11.1 mg/dL) were
      independent significant factors for detecting PICs. CONCLUSIONS: CRP on 4POD
      >=11.1 mg/dL was an independent PICs risk factor in patients who underwent MIE.
      It will be beneficial for the early detection of PICs following MIE.

PMID- 27878353
TI  - Does MRI of the Thoracolumbar Spine Change Management in Blunt Trauma Patients
      with Stable Thoracolumbar Spinal Injuries Without Neurologic Deficits?
AB  - BACKGROUND: In blunt trauma patients with computed tomography (CT) findings of
      stable thoracolumbar (TL) spinal injury without neurologic deficits, magnetic
      resonance imaging (MRI) studies are commonly obtained, though the impact on
      overall management remains unclear. The indication for MRI in patients with TL
      injury without neurologic deficits continues to remain unclear. Here, we evaluate
      the role of MRI on clinical management of patients presenting with this
      diagnosis. METHODS: After IRB approval, all registry patients from December 2005
      to December 2015 with all blunt TL injuries without defects were extracted.
      General demographics, injury parameters, hospital and ICU length of stay
      (ILOS/HLOS), CT/MRI findings, and intervention were collected. Impact of variant
      ISS in the four groups was corrected by dividing HLOS and ILOS by ISS. The
      Student's t test was conducted for statistical analysis. RESULTS: Of 613
      patients, 236 met the inclusion criteria with average age of 52 +/- 23 y, ISS (7
      +/- 4), HLOS (5 +/- 3 days), and ILOS (1 +/- 2 days). One hundred and thirty
      three patients underwent MRI, and 103 patients underwent CT only. Patients who
      underwent MRI were no more likely to attain intervention (p < 0.06) but had
      longer length of stay relative to ISS (p < 0.006). CONCLUSIONS: MRI did not
      affect rate of intervention though increased HLOS accounting for ISS. CT findings
      of stability were concordant with MRI findings. Our results suggest that MRI may
      not affect intervention decisions in blunt trauma patients with CT findings of
      stable thoracolumbar spinal injury without neurological deficits.

PMID- 27878355
TI  - Survival impact of neoadjuvant gemcitabine plus S-1 chemotherapy for patients
      with borderline resectable pancreatic carcinoma with arterial contact.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of neoadjuvant
      gemcitabine plus S-1 (GS) chemotherapy as measured by overall survival for
      patients with pancreatic carcinoma with arterial contact. METHODS: Medical
      records of 77 patients with pancreatic carcinoma with arterial contact who
      intended to undergo tumor resection were analyzed retrospectively. These patients
      were divided into two groups: patients who underwent upfront surgery and patients
      who underwent tumor resection after neoadjuvant GS chemotherapy.
      Clinicopathological factors were compared between the two groups. RESULTS: Of the
      77 patients, 25 patients underwent upfront surgery while the remaining 52
      patients received neoadjuvant GS chemotherapy. Seven patients did not undergo
      tumor resection due to distant metastasis. No serious adverse effects associated
      with neoadjuvant GS chemotherapy were observed. The R0 resection rate of patients
      who received neoadjuvant GS chemotherapy was significantly higher than that of
      patients who did not (P < 0.001). Overall survival of patients who received
      neoadjuvant GS chemotherapy was significantly longer than that of patients who
      did not among all 77 patients (P = 0.003, median survival time, 27.1 vs. 11.6
      months) as well as among the 70 patients who underwent tumor resection (P =
      0.001, median survival time, 27.2 vs. 11.6 months). Multivariate analysis
      demonstrated that neoadjuvant GS chemotherapy was an independent prognostic
      factor of overall survival for patients who underwent tumor resection (P =
      0.019). CONCLUSIONS: Neoadjuvant GS chemotherapy may provide a survival benefit
      to patients with pancreatic carcinoma with arterial contact.

PMID- 27878354
TI  - Randomized phase II study of cetuximab versus irinotecan and cetuximab in
      patients with chemo-refractory KRAS codon G13D metastatic colorectal cancer (G13D
      study).
AB  - PURPOSE: This study investigated the efficacy and safety of cetuximab-based
      treatment in patients with chemotherapy-resistant refractory mCRC with KRAS G13D
      mutation. PATIENTS AND METHODS: An assessment of the efficacy and safety of
      cetuximab-based treatment was performed in an observation-enriched randomized
      controlled study comparing the cetuximab alone group (Cet group) and the
      combination of cetuximab and irinotecan group (CetI group) for KRAS G13D-mutated
      mCRC in Japan. In this study, the patients received a biweekly (500 mg/m2 on day
      1) or weekly (250 mg/m2) intravenous infusion of cetuximab in Cet group, or a
      biweekly (500 mg/m2 on day 1) or weekly (250 mg/m2) intravenous infusion of
      cetuximab followed by irinotecan (150 mg/m2) in CetI group. Propensity score
      adjustment was used to achieve balance in the observational arm. RESULTS: Data
      from a total of 29 patients (10 in Cet group, 19 in CetI group) were analyzed.
      Crude median progression-free survival time was 2.9 months in the Cet group and
      2.5 months in the CetI group. Crude disease control rates were 55.6% in the Cet
      group and 47.4% in the CetI group. After a median follow-up of 43 months, the
      crude median overall survival was 8.0 months in the Cet group and 7.6 months in
      the CetI group. Cetuximab-based treatment did not markedly increase any
      characteristic toxicity and was generally well tolerated. Propensity score
      analyses adjusted for performance status and number of metastases showed
      comparable results with the crude results. CONCLUSION: Cetuximab-based treatment
      seemed to benefit patients with chemotherapy-resistant, refractory KRAS G13D
      mutated mCRC. Our results might support the administration of cetuximab-based
      treatment for KRAS-mutant mCRC and would be able to provide treatment flexibility
      in this setting.

PMID- 27878356
TI  - Phase I trial of daily triapine in combination with cisplatin chemotherapy for
      advanced-stage malignancies.
AB  - PURPOSE: Advanced-stage malignancies have increased deoxyribonucleotide demands
      in DNA replication and repair, making deoxyribonucleotide supply a potential
      exploitable target for therapy based on ribonucleotide reductase (RNR)
      inhibition. METHODS: A dose-finding phase I trial was conducted of intravenous
      (i.v.) triapine, a small-molecule RNR inhibitor, and cisplatin chemotherapy in
      patients with advanced-stage solid tumor malignancies. Patients received dose
      finding levels of i.v. triapine (48-96 mg/m2) and i.v. cisplatin (20-75 mg/m2) on
      1 of 3 different schedules. The primary endpoint was to identify the maximum
      tolerated dose of a triapine-cisplatin combination. Secondary endpoints included
      the rate of triapine-cisplatin objective response and the pharmacokinetics and
      bioavailability of a single oral triapine dose. (Clinicaltrials.gov number,
      NCT00024323). RESULTS: The MTD was 96 mg/m2 triapine daily days 1-4 and 75 mg/m2
      cisplatin split over day 2 and day 3. Frequent grade 3 or 4 adverse events
      included fatigue, dyspnea, leukopenia, thrombocytopenia, and electrolyte
      abnormalities. No objective responses were observed; 5 (50%) of 10 patients
      treated at the MTD had stable disease. Pharmacokinetics indicated an oral
      triapine bioavailability of 88%. CONCLUSIONS: The triapine-cisplatin combination
      may be given safely in patients with advanced-stage solid tumor malignancies. On
      the basis of these results, a phase I trial adequately powered to evaluate oral
      triapine bioavailability in women with advanced-stage uterine cervix or vulvar
      cancers is underway.

PMID- 27878357
TI  - On-treatment markers as predictors to guide anti-EGFR MoAb treatment in
      metastatic colorectal cancer: a systematic review with meta-analysis.
AB  - PURPOSE: Skin toxicity (ST) and early tumor shrinkage (ETS) are early phenomenon
      during the anti-epidermal growth factor receptor (EGFR) monoclonal antibody
      (MoAb) treatment. We conducted a meta-analysis and included relevant studies that
      reported the impact of ST and ETS on survival- and life quality-based outcome of
      metastatic colorectal cancer (mCRC) patients treated with anti-EGFR MoAb.
      METHODS: Relevant studies were identified from PubMed and Embase reporting the
      correlation of ST and ETS with the clinical outcome of mCRC patients treated with
      anti-EGFR MoAb. We also collected evidences on the impact of ST and ETS on
      absolute benefit acquired from additional anti-EGFR treatment and quality of life
      (ST only). Pooled hazard ratio and rate difference were all estimated by using
      random-effects model. RESULTS: Pooled data revealed that the occurrence of ST and
      ETS >=20% (v < 20%) during anti-EGFR MoAb treatment were both associated with
      better OS, PFS and ORR. This association could not be disturbed by KRAS status.
      Mean changes in safety follow-up life health state from baseline appeared
      unaffected by ST. Only mCRC patients with wild-type KRAS tumor who suffered grade
      2+ ST could benefit from additional anti-EGFR treatment to chemotherapy or best
      supportive care (BSC) alone. ETS was also a predictor for absolute survival
      benefit acquired from additional anti-EGFR treatment for patients with wild-type
      KRAS tumors, and the more early shrinkage the tumor was, the much benefit was
      observed. CONCLUSION: ST and ETS are predictive of absolute benefit acquired from
      anti-EGFR treatment in mCRC patients with wild-type KRAS tumors. These two on
      treatment markers can be used for clinical decision-making if no adequate
      biological markers from tissues are provided.

PMID- 27878358
TI  - Clinical research on rare diseases of children: neuroblastoma.
AB  - PURPOSE: Early access to new treatment options should not preclude accurate
      research planning, especially for rare diseases and fragile populations. Taking
      neuroblastoma as a model case, we analyzed the rationale supporting the search
      for future therapeutic strategies in the light of preclinical and clinical
      evidence. METHODS: We reviewed ongoing randomized trials of pharmacological
      interventions for the treatment of neuroblastoma retrieved by searching
      ClinicalTrials.gov and the European Union Clinical Trials Registry (last update
      March 2016). RESULTS: Our search identified four randomized clinical trial
      reports. We found poor evidence from preclinical and early clinical research
      supporting their rationale. Their methodology was questionable too. CONCLUSIONS:
      The urgency to cover unmet needs in difficult clinical settings like rare
      diseases, particularly those involving fragile populations, cannot justify
      disorderly research approaches. Under these circumstances, clinical questions
      should be properly identified and addressed to protect patients and avoid
      wasteful research.

PMID- 27878359
TI  - Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy
      resistance to doxorubicin in bladder transitional cell carcinoma.
AB  - PURPOSE: Bladder cancer is the most general malignant cancer in genitourinary
      system, more than 90% of BCs are bladder transitional cell carcinomas (BTCC).
      This study aimed to investigate the clinical significance of growth arrest
      specific 5 (GAS5) gene and its regulatory effects of malignant proliferation and
      chemotherapy resistance to doxorubicin in BTCC cells. METHODS: The expression of
      GAS5 was detected by quantitative real-time PCR. Statistical analysis was used to
      determine the relationship between GAS5 expression and clinical features and the
      prognostic value of GAS5 for disease free survival. MTT assay was used to detect
      cell proliferation ability and chemosensitivity. Dual-color flow cytometric
      method was used to detect cell apoptosis. The expression of Bcl-2 protein was
      examined by western blot. RESULTS: In this study, we found that GAS5 low
      expressed in BTCC tissues and cells, and its low expression level had positive
      correlation with higher pathological grades of BTCC. Moreover, GAS5 was a
      prognostic biomarker of disease free survival for BTCC patients. GAS5 over
      expression could inhibit cell proliferation of BTCC J82 and T24 cells
      significantly. The IC50 to doxorubicin in T24/DOX cells (resistance to
      doxorubicin) presented a conspicuous depression, GAS5 enhancement reduced the
      chemotherapy resistance to doxorubicin. GAS5 over-expression promoted apoptosis
      induced by doxorubicin in T24/DOX cells, and depressed the expression of anti
      apoptosis protein Bcl-2. The results indicated that GAS5 regulated the
      chemotherapy resistance to doxorubicin via Bcl2 partly. CONCLUSIONS: In summary,
      lncRNA GAS5 was a prognostic biomarker of disease free survival in BTCC patients,
      and acted as a tumor-suppressing gene to inhibit malignant proliferation and
      resistance to doxorubicin in BTCC cells. LncRNA GAS5 might be a novel potential
      therapeutic target for BTCC.

PMID- 27878360
TI  - Erratum to: Tremor and hand-arm vibration syndrome (HAVS) in road maintenance
      workers.

PMID- 27878361
TI  - Linguistic validation of the "FACE-Q Rhinoplasty Module" in Italian.

PMID- 27878362
TI  - A 3-D analysis of the protympanum in human temporal bones with chronic ear
      disease.
AB  - Eustachian tube dysfunction is believed to be an important factor to
      cholesteatoma development and recurrence of disease after surgical treatment.
      Although many studies have described prognostic factors, evaluation methods, or
      surgical techniques for Eustachian tube dysfunction, they relied on the soft
      tissues of its structure; little is known about its bony structure-the
      protympanum-which connects the Eustachian tube to the tympanic cavity, and can
      also be affected by several inflammatory conditions, both from the middle ear or
      from the nasopharynx. We studied temporal bones from patients with cholesteatoma,
      chronic otitis media (with and without retraction pockets), purulent otitis
      media, and non-diseased ears, looking for differences between the volume of the
      protympanum, the diameter of the Eustachian tube isthmus, and the distance
      between the anterior tympanic annulus and the promontory. Light microscopy and 3
      D reconstruction software were used for the measurements. We observed a decrease
      of volume in the lumen of the four middle ear diseased ears compared to the
      control group. We observed a significant decrease in the volume of the
      protympanic space in the cholesteatoma group compared to the chronic otitis media
      group. We also observed a decrease in the bony space (protympanum space) in
      cholesteatoma, chronic otitis media with retraction pockets, and purulent otitis
      media compared to the control group. We found a correlation in middle ear
      diseases and a decrease in the middle ear space. Our findings may suggest that a
      smaller bony volume in the protympanic area may trigger middle ear dysventilation
      problems.

PMID- 27878363
TI  - Improvement of overall survival in stage IV melanoma patients during 2011-2014:
      analysis of real-world data in 441 patients of the German Central Malignant
      Melanoma Registry (CMMR).
AB  - BACKGROUND: During 2011 and 2014, new treatment modalities like tyrosine kinase
      inhibitors and checkpoint inhibitors were introduced into the therapy of
      metastatic melanoma. This study addresses the question whether overall survival
      (OS) of metastatic melanoma patients has already been improved in 441 patients
      diagnosed with metastatic melanoma between 2011 and 2014 in the real-world
      setting at the University Hospital Tuebingen. METHODS: All patients were
      documented with their different therapies by the CMMR and followed up until March
      2016. Survival probabilities were calculated by Kaplan-Meier estimators, and log
      rank tests were used to evaluate significances. Hazard ratios were estimated by
      Cox regression analysis for survival probabilities and prognostic factors in
      stage IV melanoma. RESULTS: Best OS was observed in patients (n = 93) treated by
      metastasectomy as primary treatment with the intention to completely excise all
      metastases (3-year OS 61%). OS for patients with first-line systemic treatment (n
      = 258) was unfavorable in general (3-year OS 23%). Of those, the most favorable
      outcome was observed in patients without brain metastasis and treated with
      immunotherapy (mostly ipilimumab), as first-line treatment (median OS 35 months,
      3-year OS 43%). In case of brain metastases, patients with targeted therapy had a
      better OS (median 14 months) than patients with ipilimumab treatment (median 7
      months). Among all patients with first-line systemic treatment, outcome of
      patients diagnosed in the years 2013/2014, compared to 2011 and 2012, showed an
      improved survival. Three-year OS for patients that entered stage IV in 2013/2014
      was 37% compared to those that entered stage IV in 2011 (18%) and 2012 (20%).
      CONCLUSION: The analysis of real-world data of treatment of metastatic melanoma
      showed an improvement of OS with both immunotherapy and targeted therapy. In case
      of cerebral metastasis, patients treated with targeted therapy showed a longer
      median OS than patients treated with ipilimumab.

PMID- 27878364
TI  - [AV-reentrant tachycardia and Wolff-Parkinson-White syndrome : Diagnosis and
      treatment].
AB  - The AV-reentrant tachycardia (AVRT) is a supraventricular tachycardia with an
      incidence of 1-3/1000. The pathophysiological basis is an accessory
      atrioventricular pathway (AP). Patients with AVRT typically present with
      palpitations, an on-off characteristic, anxiety, dyspnea, and polyuria. This type
      of tachycardia may often be terminated by vagal maneuvers. Although the clinical
      presentation of AVRT is quite similar to AV-nodal reentrant tachycardias, the
      correct diagnosis is often facilitated by analyzing a standard 12-lead ECG at
      normal heart rate showing ventricular preexcitation. Curative catheter ablation
      of the AP represents the therapy of choice in symptomatic patients. This article
      is the fourth part of a series written to improve the professional education of
      young electrophysiologists. It explains pathophysiology, symptoms, and
      electrophysiological findings of an invasive EP study. It focusses on mapping and
      ablation of accessory pathways.

PMID- 27878365
TI  - [Implantable loop recorders of the Reveal family (Medtronic)].
AB  - This review explains the implantable loop recorders Medtronic Reveal XT and
      Medtronic Reveal LINQ. Technical specifications of the two devices are described
      in great detail. Additional tips for implantation as well as device programming
      are given including specific considerations of follow-up.

PMID- 27878367
TI  - ?

PMID- 27878366
TI  - Widespread tau seeding activity at early Braak stages.
AB  - Transcellular propagation of tau aggregates may underlie the progression of
      pathology in Alzheimer's disease (AD) and other tauopathies. Braak staging (B1,
      B2, B3) is based on phospho-tau accumulation within connected brain regions:
      entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal
      lobes (B3). We previously developed a specific and sensitive assay that uses flow
      cytometry to quantify tissue seeding activity based on fluorescence resonance
      energy transfer (FRET) in cells that stably express tau reporter proteins. In a
      tauopathy mouse model, we have detected seeding activity far in advance of
      histopathological changes. It remains unknown whether individuals with AD also
      develop seeding activity prior to accumulation of phospho-tau. We measured tau
      seeding activity across four brain regions (hippocampus, frontal lobe, parietal
      lobe, and cerebellum) in 104 fresh-frozen human AD brain samples from all Braak
      stages. We observed widespread seeding activity, notably in regions predicted to
      be free of phospho-tau deposition, and in detergent-insoluble fractions that
      lacked tau detectable by ELISA. Seeding activity correlated positively with Braak
      stage and negatively with MMSE. Our results are consistent with early
      transcellular propagation of tau seeds that triggers subsequent development of
      neuropathology. The FRET-based seeding assay may also complement standard
      neuropathological classification of tauopathies.

PMID- 27878368
TI  - [Therapy options for malignant eyelid tumors].
AB  - Basal cell carcinomas are the most common malignant tumors of the eyelids.
      Patient history, clinical symptoms and signs, inspection, palpation and slit-lamp
      examination usually allow a working diagnosis; however, the clinical diagnosis
      requires histopathological confirmation and determination of the
      histopathological type. Squamous cell carcinomas, sebaceous gland carcinomas,
      melanomas and Merkel cell carcinomas can metastasize usually via the lymph
      vessels into the regional lymph nodes. Microscopically controlled excision of the
      primary tumor into healthy tissue is most commonly the first goal. Palpation and
      ultrasonography of the regional lymph nodes and also computed tomography (CT)
      with contrast enhancement and magnetic resonance imaging (MRI) for tumors with
      perineural sheath cell invasion are necessary to define the TNM stage. Non
      surgical treatment options are becoming more popular in the further management of
      malignant eyelid tumors.

PMID- 27878369
TI  - YOUTUBE videos on oral care of the organ or hematopoietic stem cell transplant
      patients.
AB  - OBJECTIVE: Video-sharing websites can be a useful platform for disseminating
      information. The aim of this study was to evaluate information about the oral
      health care of the organ transplant and hematopoietic stem cell transplant
      patients available on YouTubeTM. METHODS: The transversal study evaluated the
      content of YouTubeTM videos. The videos were located by entering key search terms
      in the YouTubeTM search engine-oral care/dental management/organ
      transplant/hematopoietic stem cell transplant patients. The videos were then
      classified as useful, misleading, or as personal experiences reported by
      patients. The following information was registered: the source of the video,
      content, interaction, and overall quality. RESULTS: A total of 50 videos were
      reviewed; 16 (33.14%) were classed as useful, 22 (44%) were misleading, and 12
      (24%) reported patients' personal experiences. Significant differences were found
      in overall quality (p = 0.012). When interaction variables were analyzed
      statistically significant differences were found for the following: "I did not
      like this video" (p <= 0.05) and comments (p <= 0.05). CONCLUSIONS: Several
      videos reviewed information on oral care of organ transplant and hematopoietic
      stem cell transplant patients but were sometimes difficult to interpret.
      Nevertheless, YouTubeTM is a tool that can help supply information and promote
      oral health care education among of organ transplant and hematopoietic stem cell
      transplant patients.

PMID- 27878370
TI  - Validation of the symbolic assessment of fatigue extent (SAFE)-a cancer fatigue
      tool with visual response formats.
AB  - CONTEXT: Fatigue is the most common under-recognized symptom in cancer.
      Administering fatigue tools in multi-lingual and multi-literate populations may
      affect the quality and accuracy of the data collected as they rely on language to
      elicit responses. AIM: The aim of the study is to develop and validate a tool to
      assess fatigue in cancer patients using response formats that are not language
      dependent. METHODS: The content validity of the tool was established using the
      Delphi procedure and was field tested with 102 cancer patients. Test-retest
      reliability of the tool was tested with 55 cancer patients and 47 healthy
      individuals. Convergent, concurrent, and discriminant validity and internal
      consistency were established with 374 cancer patients, 202 survivors, and 75
      healthy controls. STATISTICAL ANALYSIS: Qualitative analyses, descriptive
      statistics, product-moment correlation, analysis of variance, Cronbach's alpha
      coefficient, and exploratory factor analysis were conducted. RESULTS: The
      Cronbach's alpha of the SAFE in cancer patients and healthy individuals was .86
      and .92, and their test-retest reliability ranged from .44 to .83. SAFE
      correlated significantly with measures of quality of life (QOL) (r = -0.54, p <
      .01), anxiety (r = 0.54, p < .01), depression (r = 0.5, p < .01), and sleep (r =
      0.52, p < .01). The tool was able to distinguish between cancer patients,
      survivors, and healthy controls (p < .05). Two factors emerged namely "Fatigue
      Extent and impact" and "General fatigue" contributing to 52% of the variance in
      fatigue. CONCLUSION: A symbolic tool using visual response formats to assess
      fatigue and its impact in cancer patients was developed and standardized with
      good reliability and construct, concurrent, and discriminant validity
      established.

PMID- 27878371
TI  - Characterization of GlobalFiler loci in Angolan and Guinean populations
      inhabiting Southern Portugal.
AB  - We analyzed the GlobalFiler short tandem repeat (STR) loci for 152 and 70
      unrelated individuals from Angolan and Guinean immigrant populations inhabiting
      Southern Portugal, respectively. After Bonferroni correction, no significant
      deviations from the Hardy-Weinberg equilibrium and linkage disequilibrium were
      detected for either population. For the Angolan population, SE33 was the most
      informative marker. In contrast, D5S818 and D13S317 were the least informative
      loci. The combined power of discrimination was 99.9999999999999999999999961907%.
      For the Guinean population, SE33 and D21S1 were the most informative loci, while
      D13S317 was the least. The combined power of discrimination was
      99.99999999999999999999997915%. No significant differences were observed between
      Angolan, Guinean, and Afro-American populations for any of the analyzed STRs. The
      South African population presented significant differences at D22S1045 and
      D10S1248 when compared to Angola, and at D22S1045 when compared to Guinea-Bissau.
      The MDS plot and neighbor-joining tree analysis revealed that Angolan and Guinean
      populations are genetically close to African-American and South African
      populations, and genetically different from Korean, Mexican, European (including
      American-Caucasian), and Middle Eastern populations.

PMID- 27878372
TI  - Combined effects of multiple linked loci on pairwise sibling tests.
AB  - The advanced multiplex STR system, PowerPlex Fusion, includes four linked locus
      pairs. The conventional Identifiler system has one pair of linked loci.
      Therefore, sibling tests conducted using the advanced system might be more
      affected by linkage than those conducted using the conventional system. This
      study simulated single and combined effects of the four linked locus pairs on
      pairwise sibling tests. Simulated genotypes of 100,000 pairs of full siblings and
      nonrelatives were constructed according to allele frequencies of the Japanese
      population. The single linkage effect was evaluated for simulated genotype data
      by calculating both the likelihood ratio accounting for the linkage between two
      loci and the likelihood ratio ignoring the linkage. The combined effect was
      obtained by multiplication of the respective single effects. Furthermore, we
      investigated the possibility that ignoring the linkage affects subject
      classification by introducing a scale of the likelihood ratio into sibling tests.
      The single effect in the Identifiler analysis was 0.645-1.746 times if the
      linkage was ignored. Overestimations and underestimations were predictable from
      the identical-by-state status at two linked loci. The combined effect in the
      PowerPlex Fusion analysis was 0.217-7.390 times. Ignoring the linkage rarely
      caused a false conclusive or inconclusive result, even from PowerPlex Fusion
      analysis. Application of the advanced system improved sibling tests considerably.
      The additional examined loci were more beneficial than the adverse effect of the
      linkage derived from the four linked locus pairs.

PMID- 27878373
TI  - Restrictive allograft syndrome after lung transplantation: new radiological
      insights.
AB  - OBJECTIVES: To describe the CT changes in patients with restrictive allograft
      syndrome (RAS) after lung transplantation, before and after clinical diagnosis.
      METHODS: This retrospective study included 22 patients with clinical diagnosis of
      RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1)
      decline (>=20 %) and total lung capacity (TLC) decline (>=10 %). All available CT
      scans after transplantation were analyzed for the appearance and evolution of
      lung abnormalities. RESULTS: In 14 patients, non-regressing nodules and
      reticulations predominantly affecting the upper lobes developed an average of
      13.9 months prior to the diagnosis of RAS. Median graft survival after onset of
      non-regressing abnormalities was 33.5 months, with most patients in follow-up
      (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly
      affecting both upper and lower lobes was seen an average of 2.8 months prior to
      the diagnosis of RAS. Median graft survival was 6.4 months after first onset of
      non-regressing abnormalities, with graft loss in most patients (6/8).
      CONCLUSIONS: RAS has been previously described as a homogenous group. However,
      our study shows two different groups of RAS-patients: one with slow progression
      and one with fast progression. The two groups show different onset and
      progression patterns of CT abnormalities. KEY POINTS: * RAS is the newest
      discovered form of chronic lung allograft dysfunction (CLAD). * RAS is not a
      homogenous group, as survival varies greatly between patients. * In this study,
      we see two different CT onset and progression patterns. * These two different CT
      patterns also correlate with a different survival rate.

PMID- 27878375
TI  - Hyper-thermal acid hydrolysis and adsorption treatment of red seaweed, Gelidium
      amansii for butyric acid production with pH control.
AB  - Optimal hyper-thermal (HT) acid hydrolysis conditions for Gelidium amansii were
      determined to be 12% (w/v) seaweed slurry content and 144 mM H2SO4 at 150 
      degrees C for 10 min. HT acid hydrolysis-treated G. amansii hydrolysates produced
      low concentrations of inhibitory compounds and adsorption treatment using 3%
      activated carbon. An adsorption time of 5 min was subsequently used to remove the
      inhibitory 5-hydroxymethylfurfural from the medium. A final maximum
      monosaccharide concentration of 44.6 g/L and 79.1% conversion from 56.4 g/L total
      fermentable monosaccharides with 120 g dw/L G. amansii slurry was obtained from
      HT acid hydrolysis, enzymatic saccharification, and adsorption treatment. This
      study demonstrates the potential for butyric acid production from G. amansii
      hydrolysates under non-pH-controlled as well as pH-controlled fermentation using
      Clostridium acetobutylicum KCTC 1790. The activated carbon treatment and pH
      controlled fermentation showed synergistic effects and produced butyric acid at a
      concentration of 11.2 g/L after 9 days of fermentation.

PMID- 27878374
TI  - Agents for fluorescence-guided glioma surgery: a systematic review of preclinical
      and clinical results.
AB  - BACKGROUND: Fluorescence-guided surgery (FGS) is a technique used to enhance
      visualization of tumor margins in order to increase the extent of tumor resection
      in glioma surgery. In this paper, we systematically review all clinically tested
      fluorescent agents for application in FGS for glioma and all preclinically tested
      agents with the potential for FGS for glioma. METHODS: We searched the PubMed and
      Embase databases for all potentially relevant studies through March 2016. We
      assessed fluorescent agents by the following outcomes: rate of gross total
      resection (GTR), overall and progression-free survival, sensitivity and
      specificity in discriminating tumor and healthy brain tissue, tumor-to-normal
      ratio of fluorescent signal, and incidence of adverse events. RESULTS: The search
      strategy resulted in 2155 articles that were screened by titles and abstracts.
      After full-text screening, 105 articles fulfilled the inclusion criteria
      evaluating the following fluorescent agents: 5-aminolevulinic acid (5-ALA) (44
      studies, including three randomized control trials), fluorescein (11),
      indocyanine green (five), hypericin (two), 5-aminofluorescein-human serum albumin
      (one), endogenous fluorophores (nine) and fluorescent agents in a pre-clinical
      testing phase (30). Three meta-analyses were also identified. CONCLUSIONS: 5-ALA
      is the only fluorescent agent that has been tested in a randomized controlled
      trial and results in an improvement of GTR and progression-free survival in high
      grade gliomas. Observational cohort studies and case series suggest similar
      outcomes for FGS using fluorescein. Molecular targeting agents (e.g.,
      fluorophore/nanoparticle labeled with anti-EGFR antibodies) are still in the pre
      clinical phase, but offer promising results and may be valuable future
      alternatives.

PMID- 27878379
TI  - Uncommon cause of fever in a pediatric kidney transplant recipient: Questions.

PMID- 27878377
TI  - Relationship between the plasma levels of neurodegenerative proteins and motor
      subtypes of Parkinson's disease.
AB  - The aim of our study is to examine the plasma levels of the four kinds of
      neurodegenerative proteins in plasma: alpha-syn, T-tau, P-tau181, and Abeta-42 in
      Parkinson's disease (PD) and to evaluate the relationship between their plasma
      levels and PD motor subtypes. 84 patients with PD were enrolled in our study, and
      finally, 73 of them were classified into the tremor-dominant subtype (TD) and the
      postural instability gait difficulty subtype (PIGD). Their motor performance was
      evaluated by a series of clinical assessments: Freezing of Gait Questionnaire
      (FOGQ), Timed Up and Go (TUGs), Tinetti balance, and Tinetti gait. Plasma levels
      of these proteins were measured by enzyme-linked immunosorbent assay (ELISA). The
      plasma level of alpha-syn was significantly higher in PD patients when compared
      to controls (p = 0.004), and significantly higher in the PIGD group when compared
      to the TD group (p = 0.03). While the plasma level of Abeta-42 was significantly
      lower in PD patients than in controls (p = 0.002), and significantly lower in the
      PIGD group than in the TD group (p = 0.05). In PD patients, the plasma level of
      alpha-syn (r = -0.355, p < 0.001) was significantly related to the severity of
      Tenitti Gait score, even after performing multiple linear regression (p = 0.002).
      While the plasma level of Abeta-42 (r = -0.261, p < 0.05) was significantly
      associated with the severity of PIGD score and remained correlate when performed
      multiple linear regression (p = 0.005). The patients with PIGD subtype are
      characterized with a lower level of plasma Abeta-42 and a higher plasma level of
      alpha-syn, which may be used as biomarkers for diagnosis and progression of the
      subtypes of PD.

PMID- 27878376
TI  - Amygdala structure and aggressiveness in borderline personality disorder.
AB  - Aggressiveness is considered an important clinical feature of borderline
      personality disorder (BPD) and has been associated with alterations of the
      amygdala. However, studies that analyzed the exact location of amygdala
      alterations associated with aggressiveness in BPD or that systematically compared
      female and male BPD patients are missing. In the current study, we therefore
      investigated a sex-mixed sample of BPD patients and healthy volunteers and
      applied an automated segmentation method that allows the study of both,
      alterations of amygdala volume and localized amygdala shape. Volumetric results
      revealed no difference in amygdala volume between BPD patients and healthy
      volunteers, but a trend for a positive association between volume of the right
      amygdala and aggressiveness in male BPD patients. Analyses of amygdala shape
      showed a trend for a group by sex interaction effect in the left laterobasal
      amygdala, without a difference in subgroup analyses. Finally, regions of the left
      superficial and laterobasal amygdala of male BPD patients were positively
      associated with aggressiveness. In sum, our results emphasize the need to
      consider sex-specific effects and demonstrate a link between male BPD patients'
      aggressiveness and amygdala regions that are particularly related to social
      information processing and associative emotional learning.

PMID- 27878378
TI  - Phonotactic flight of the parasitoid fly Emblemasoma auditrix (Diptera:
      Sarcophagidae).
AB  - The parasitoid fly Emblemasoma auditrix locates its hosts using acoustic cues
      from sound producing males of the cicada Okanagana rimosa. Here, we
      experimentally analysed the flight path of the phonotaxis from a landmark to the
      target, a hidden loudspeaker in the field. During flight, the fly showed only
      small lateral deviations. The vertical flight direction angles were initially
      negative (directed downwards relative to starting position), grew positive
      (directed upwards) in the second half of the flight, and finally flattened
      (directed horizontally or slightly upwards), typically resulting in a landing
      above the loudspeaker. This phonotactic flight pattern was largely independent
      from sound pressure level or target distance, but depended on the elevation of
      the sound source. The flight velocity was partially influenced by sound pressure
      level and distance, but also by elevation. The more elevated the target, the
      lower was the speed. The accuracy of flight increased with elevation of the
      target as well as the landing precision. The minimal vertical angle difference
      eliciting differences in behaviour was 10 degrees . By changing the elevation of
      the acoustic target after take-off, we showed that the fly is able to orientate
      acoustically while flying.

PMID- 27878380
TI  - Uncommon cause of fever in a pediatric kidney transplant recipient: Answers.

PMID- 27878381
TI  - Posttraumatic stress and quality of life with the totally subcutaneous compared
      to conventional cardioverter-defibrillator systems.
AB  - BACKGROUND: For prevention of sudden cardiac death, the transvenously implantable
      cardioverter-defibrillator therapy (tv-ICD) is well accepted. The subcutaneous
      system (S-ICD(r)) is promising in terms of reducing ICD complications.
      Nevertheless, the impact of the novel generator position on patients' quality of
      life (QoL) is yet unknown. OBJECTIVE: This study aimed at comparing QoL and
      posttraumatic stress with both systems. METHODS: 60 S-ICD(r) and 60 case
      controlled tv single-chamber ICD patients were asked to respond to three
      standardized questionnaires. PDS [screening for posttraumatic stress disorders
      (PTSD)] and PHQ-D (detection of the most predominant psychological disorders)
      were used to screen for potential mental comorbidities. The SF-12 questionnaire
      was used to evaluate physical and mental well-being. Groups were compared in
      terms of QoL and PTSD. RESULTS: n = 42 (70%) pairs were analyzed (n = 30 male,
      mean age 44.6 +/- 12.2 years). Prior appropriate (p = 0.06) or inappropriate
      episodes (p = 0.24), ejection fraction (p = 0.28), or underlying cardiac disease
      did not differ significantly between groups. PDS revealed a PTSD in n = 6 tv-ICD
      and n = 6 S-ICD(r) patients (14.3%) equally. In the PHQ-D questionnaire, n = 4 tv
      ICD and n = 2 S-ICD(r) patients fulfilled criteria for a major depression (p =
      0.68). Panic disorders (n = 2 tv, n = 0 S-ICD(r), p = 0.5), and anxiety disorders
      (n = 3 S-ICD(r), n = 0 tv-ICD, p = 0.24) did not differ between groups. The
      physical well-being score was 39.9 +/- 12.5 in patients with a tv-ICD compared to
      46.6 +/- 9.9 in S-ICD(r) patients (p = 0.01). The mental well-being score was
      comparable in both groups (tv-ICD 51.8 +/- 10.8 vs. S-ICD(r) 51.9 +/- 10.4, p =
      0.95). CONCLUSIONS: Our case-control study revealed equal or even better physical
      well-being of patients with the S-ICD(r). PTSD occurred in almost 15% of ICD
      patients irrespective of the type of system.

PMID- 27878382
TI  - Ultra-marathon 100 km in an islet-transplanted runner.

PMID- 27878384
TI  - Direct consumptive interactions between mammalian herbivores and plant-dwelling
      invertebrates: prevalence, significance, and prospectus.
AB  - Mammalian herbivores induce changes in the chemical composition, phenology,
      distribution, and abundance of the plants they feed on. Consequently,
      invertebrate herbivores (predominantly insects) that depend on those plants, and
      the predators and parasitoids that are associated with them, may be affected.
      This plant-mediated indirect interaction between mammals and invertebrates has
      been extensively studied, but mammalian herbivores may also directly affect plant
      dwelling invertebrates (PDI) by incidentally ingesting them while feeding. The
      ubiquity and small size of PDI render them highly susceptible to incidental
      ingestion, but as common as this interaction may intuitively seem, very little is
      known about its prevalence and ecological consequences. Nevertheless, cases of
      incidental ingestion of PDI and associated adaptations for avoiding it that have
      been sporadically documented in several invertebrate groups and life stages allow
      us to carefully extrapolate and conclude that it should be common in nature.
      Incidental ingestion may, therefore, bear significant consequences for PDI, but
      it may also affect the mammalian herbivores and the shared plants. Future
      research on incidental ingestion of PDI would have to overcome several technical
      difficulties to gain better insight into this understudied ecological
      interaction.

PMID- 27878385
TI  - The effects of warming on the ecophysiology of two co-existing kelp species with
      contrasting distributions.
AB  - The northeast Atlantic has warmed significantly since the early 1980s, leading to
      shifts in species distributions and changes in the structure and functioning of
      communities and ecosystems. This study investigated the effects of increased
      temperature on two co-existing habitat-forming kelps: Laminaria digitata, a
      northern boreal species, and Laminaria ochroleuca, a southern Lusitanian species,
      to shed light on mechanisms underpinning responses of trailing and leading edge
      populations to warming. Kelp sporophytes collected from southwest United Kingdom
      were maintained under 3 treatments: ambient temperature (12  degrees C), +3 
      degrees C (15  degrees C) and +6  degrees C (18  degrees C) for 16 days. At
      higher temperatures, L. digitata showed a decline in growth rates and Fv/Fm, an
      increase in chemical defence production and a decrease in palatability. In
      contrast, L. ochroleuca demonstrated superior growth and photosynthesis at
      temperatures higher than current ambient levels, and was more heavily grazed.
      Whilst the observed decreased palatability of L. digitata held at higher
      temperatures could reduce top-down pressure on marginal populations, field
      observations of grazer densities suggest that this may be unimportant within the
      study system. Overall, our study suggests that shifts in trailing edge
      populations will be primarily driven by ecophysiological responses to high
      temperatures experienced during current and predicted thermal maxima, and
      although compensatory mechanisms may reduce top-down pressure on marginal
      populations, this is unlikely to be important within the current biogeographical
      context. Better understanding of the mechanisms underpinning climate-driven range
      shifts is important for habitat-forming species like kelps, which provide organic
      matter, create biogenic structure and alter environmental conditions for
      associated communities.

PMID- 27878383
TI  - Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre
      diabetes and type 2 diabetes mellitus.
AB  - AIMS: The purpose of the current study was to investigate the characteristic
      expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes
      mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre
      diabetes and T2DM. METHODS: CircRNAs in the peripheral blood from six healthy
      individuals and six T2DM patients were collected for microarray analysis, and an
      independent cohort study consisting of 20 normal cases, 20 pre-diabetes patients
      and 20 T2DM patients was conducted to verify the five chosen circRNAs. We then
      tested hsa_circ_0054633 in a third cohort (control group, n = 60; pre-diabetes
      group, n = 63; and T2DM group, n = 64) by quantitative real-time polymerase chain
      reaction (Q-PCR). RESULTS: In total, 489 circRNAs were discovered to be
      differentially expressed between the two groups, and of these, 78 were
      upregulated and 411 were downregulated in the T2DM group. Five circRNAs were then
      selected as candidate biomarkers and further verified in a second cohort.
      Hsa_circ_0054633 was found to have the largest area under the curve (AUC). The
      diagnostic capacity of hsa_circ_0054633 was tested in a third cohort. After
      introducing the risk factors of T2DM, the hsa_circ_0054633 AUCs for the diagnosis
      of pre-diabetes and T2DM slightly increased from 0.751 (95% confidence interval
      [0.666-0.835], P < 0.001) to 0.841 ([0.773-0.910], P < 0.001) and from 0.793
      ([0.716-0.871], P < 0.001) to 0.834 ([0.762-0.905], P < 0.001), respectively.
      CONCLUSIONS: Hsa_circ_0054633 presented a certain diagnostic capability for pre
      diabetes and T2DM.

PMID- 27878386
TI  - Associated symptoms of depression: patterns of change during pregnancy.
AB  - Little is known about the natural course of depressive symptoms and associated
      features throughout pregnancy. We examined the course of some psychological and
      somatic symptoms in each month of pregnancy in a normative sample. A consecutive,
      unselected sample of women (N = 374) were interviewed retrospectively at 6 weeks
      postpartum with the Structured Clinical Interview (DSM-IV). Women were asked
      whether they had experienced each symptom at any time during pregnancy and the
      occurrence of the symptom for each month of pregnancy. Associated symptoms of
      depression showed complex changes across pregnancy. Depressed mood (F(df) =
      5.15(1); p = 0.02) showed a quadratic pattern with elevations at the beginning
      and end of pregnancy. Both linear increases (a) and quadratic (b) changes over
      time were observed for sensitivity to criticism (F a(df) = 20.9(1), p a = 0.00; F
      b(df) = 7.02(1), p b = 0.00), lack of concentration (F a(df) = 37.0(1), p a =
      0.00; F b(df) = 10.3(1); p b = 0.00), decreased energy (F a(df) = 13.4(1); p a =
      0.00; F b(df) = 62.6(1); p b = 0.00) and feelings of heavy limbs (F a (df) =
      92.9(1); p a = 0.00; F b(df) = 67.7(1); p b = 0.00). Only guilt (F(df) = 0.00(1);
      p = 0.93) showed no significant change over pregnancy. Psychological symptoms
      changed throughout pregnancy as much as somatic symptoms. A linear increase was
      found for most symptoms, but significant non-linear changes were also found. The
      discrepancy between the patterns of depressed mood and most somatic and
      psychological symptoms suggest complex interactions and potentially important
      implications for assessment and monitoring treatment.

PMID- 27878388
TI  - Influence of geomagnetic activity and earth weather changes on heart rate and
      blood pressure in young and healthy population.
AB  - There are many references in the literature related to connection between the
      space weather and the state of human organism. The search of external factors
      influence on humans is a multi-factor problem and it is well known that humans
      have a meteo-sensitivity. A direct problem of finding the earth weather
      conditions, under which the space weather manifests itself most strongly, is
      discussed in the present work for the first time in the helio-biology. From a
      formal point of view, this problem requires identification of subset
      (magnetobiotropic region) in three-dimensional earth's weather parameters such as
      pressure, temperature, and humidity, corresponding to the days when the human
      body is the most sensitive to changes in the geomagnetic field variations and
      when it reacts by statistically significant increase (or decrease) of a
      particular physiological parameter. This formulation defines the optimization of
      the problem, and the solution of the latter is not possible without the
      involvement of powerful metaheuristic methods of searching. Using the algorithm
      of differential evolution, we prove the existence of magnetobiotropic regions in
      the earth's weather parameters, which exhibit magneto-sensitivity of systolic,
      diastolic blood pressure, and heart rate of healthy young subjects for three
      weather areas (combinations of atmospheric temperature, pressure, and humidity).
      The maximum value of the correlation confidence for the measurements attributable
      to the days of the weather conditions that fall into each of three
      magnetobiotropic areas is an order of 0.006, that is almost 10 times less than
      the confidence, equal to 0.05, accepted in many helio-biological researches.

PMID- 27878387
TI  - Genetic susceptibility to cutaneous radiation injury.
AB  - The use of ionizing radiation is critical to cancer treatment and fluoroscopic
      procedures. However, despite efforts to minimize total radiation dose, many
      patients experience toxic cutaneous side-effects of ionizing radiation, ranging
      from mild erythema to subcutaneous fibrosis, telangiectasia formation, and
      ulceration. Extent of injury is highly variable among patients. Studying the
      genetic determinants of radiation injury can help develop protocols to reduce
      radiation toxicity, as well as drive research into effective modulators of the
      genes and gene products associated with radiation injury. Many studies in the
      past two decades have identified single-nucleotide polymorphisms that may be
      associated with susceptibility to cutaneous radiation injury, such as those in
      genes related to the following cellular responses to ionizing radiation:
      inflammation, DNA repair, oxidation and stress response, and cell-cycle and
      apoptosis. This review summarizes the current literature on potential major genes
      and polymorphisms, in the previously described damage response pathways, that are
      involved in susceptibility to cutaneous radiation injury. Potential pitfalls of
      current research and further avenues of discovery will be explored.

PMID- 27878389
TI  - Spleen atrophy related immune system changes attributed to infection of
      Angiostrongylus cantonensis in mouse model.
AB  - The spleen is one of the most important peripheral immune organs, which is
      frequently affected in infectious diseases. Infectious diseases can induce
      splenic alterations including splenic atrophy and functional alteration, while
      splenic atrophy may in turn interferes with recovery of infectious diseases.
      Angiostrongyliasis is an infectious disease by Angiostrongylus cantonensis (A.
      cantonensis), which invade non-permissive hosts, such as humans and mice, to
      cause severe damage to the central nervous system (CNS) and acute inflammatory
      response. A. cantonensis infection-induced CNS injury has been confirmed to be
      due to profound immunopathology derived from peripheral immune components.
      However, the mechanism of immunopathology remains largely unknown. Here, we found
      that A. cantonensis invaded non-permissive hosts such as mice in the brain, but
      not in the other peripheral organs. However, this infection induced severe spleen
      atrophy. We further recognized that this atrophy is associated with a decrease of
      total splenocyte number and disruption of splenic structure due to reduced
      proliferation and increased apoptotosis. These also resulted in deterioration of
      T cell profile in the periphery with a low CD4/CD8 ratio and B/T cell ratio, and
      increased ratio of CD4+CD25+Foxp3+ Treg, CD8+CD28- T, and CD38+T lymphocyte of
      spleen. Albendazole treatment can alleviate spleen atrophy and set T cell immune
      reconstitution in some extend. Our data showed that A. cantonensis infection can
      cause splenic atrophy. These results are suggested to put more emphasis to
      improve the function of immune system. Meanwhile, infection and treatment model
      will be useful to evaluate new therapeutic approaches which can prevent or
      reverse immunosuppression and infectious complications.

PMID- 27878391
TI  - Erratum to: 47. Jahrestagung der Osterreichischen Gesellschaft fur Innere
      Medizin.

PMID- 27878390
TI  - Trematodes from the Northern Lapwing, Vanellus vanellus (Charadriidae), from
      Central Germany.
AB  - Seventy-five previously frozen Northern Lapwings, Vanellus vanellus (Linnaeus,
      1758) were dissected and examined for trematodes. The available birds were
      euthanized after suffering severe injuries from a hail storm. Trematode specimens
      were found in the air sacs, body cavities and kidneys. They were cleared, stained
      in Alaun-Carmine and examined via light microscopy. Trematodes were assigned to
      two different families and three different species: Uvitellina vanelli and
      Selfcoelum sp. from the family Cyclocoelidae and Tanaisia valida of the family
      Eucotylidae. A prevalence of 12% (for both, Cyclocoelid and Eucotylid infections)
      was detected. While trematodes of the respiratory system have been discovered in
      V. vanellus before, the present study describes renal trematodiasis in this bird
      species for the first time. Furthermore, the first recovering of a trematode of
      the species Selfcoelum sp. in the Northern Lapwing is described. Full
      measurements and figures of trematodes are given. Criteria and critical points in
      specifying and recovering the parasites are discussed.

PMID- 27878392
TI  - Effective treatment of intractable cutaneous metastases of breast cancer with
      electrochemotherapy: Ten-year audit of single centre experience.
AB  - PURPOSE: Electrochemotherapy (ECT) is the application of electric pulses to
      tumour tissue to render the cell membranes permeable to usually impermeant
      hydrophilic anti-cancer drugs, thereby enhancing cytotoxic effects. We sought to
      ascertain whether ECT can be an effective palliative treatment for cutaneous
      metastases of breast cancer. METHODS: This work reports data from the European
      Standard Operating Procedures for Electrochemotherapy trial (EudraCT Number: 2004
      002183-18). In combination with systemic and/or intratumoural bleomycin,
      optimised electric pulses were delivered to locally recurrent or metastatic
      cutaneous breast cancer lesions. Follow-up continued until December 2014.
      RESULTS: Between February 2004 and December 2014, twenty-four patients were
      treated. All patients had received prior multimodal therapy. In total, the
      patient cohort had, or developed, 242 lesions. Two hundred and 36 lesions were
      treated, with 34 lost to follow-up. An objective response was seen in 161 of 202
      lesions (79.7%), with a complete response observed in 130 (64.3%). Thirty-nine
      lesions (19.3%) did not respond, while 2 (1%) progressed following ECT. 17
      (73.9%) patients received two or fewer treatments. A minimum of a partial
      response was seen in at least 50% of treated lesions in 18 of the 24 (75%)
      patients. Smaller lesions were more likely to have an objective response (Chi
      square test for trend, p < 0.001). CONCLUSIONS: Electrochemotherapy is an
      effective treatment for cutaneous breast cancer lesions that have proven
      refractory to standard therapies. As smaller lesions were found to be more
      responsive, we suggest that ECT should be considered as an early treatment
      modality, within multimodal treatment strategies.

PMID- 27878393
TI  - Access, use, and challenges of claims data analyses in Germany.

PMID- 27878394
TI  - Sex differences in the association of obesity and colorectal cancer risk.
AB  - Epidemiological research has convincingly shown that obesity increases colorectal
      cancer (CRC) risk, with generally stronger associations observed in men than in
      women. Evidence from the past several years has demonstrated a divergent pattern
      between men and women regarding the weight changes throughout life or timing of
      obesity for CRC risk. For men, weight gain later in life appears to be an
      important risk factor for CRC that mostly accounts for their generally strong
      association between adult body mass index and CRC risk. For women, however, early
      life obesity seems to be more important than adult weight gain in determining CRC
      risk. A knowledge of these sex patterns may have implications on better
      understanding colorectal carcinogenesis and may further improve prevention
      efforts for CRC.

PMID- 27878396
TI  - New dinitrosyl iron complexes bound with physiologically active dipeptide
      carnosine.
AB  - Dinitrosyl iron complexes (DNICs) are physiological NO derivatives and account
      for many NO functions in biology. Polyfunctional dipeptide carnosine (beta-alanyl
      L-histidine) is considered to be a very promising pharmacological agent. It was
      shown that in the system containing carnosine, iron ions and Angeli's salt, a new
      type of DNICs bound with carnosine as ligand {(carnosine)2-Fe-(NO)2}, was formed.
      We studied how the carbonyl compound methylglyoxal influenced this process.
      Carnosine-bound DNICs appear to be one of the cell's adaptation mechanisms when
      the amount of reactive carbonyl compounds increases at hyperglycemia. These
      complexes can also participate in signal and regulatory ways of NO and can act as
      protectors at oxidative and carbonyl stress conditions.

PMID- 27878397
TI  - [Primary Health Care in Austria - Tu Felix Austria nube - Concept for networking
      in the primary care of Upper Austria].
AB  - The primary health care in rural areas in Austria is currently determined by
      challenges such as ageing of the population, the shift towards chronic and age
      related illnesses, the specialist medical and hospital-related education and
      training of physicians' as well growing widespread difficulty of staffing
      doctor's office. The objective is to realize a general practitioner centered and
      team-oriented primary health care (PHC) approach by establishing networked
      primary health care in rural areas of Austria. Using literature research, online
      survey, expert interviews and expert workshops, we identified different
      challenges in terms of primary health care in rural areas. Further, current
      resources and capacities of primary health care in rural areas were identified
      using the example of the district of Rohrbach. Twelve design dimensions and 51
      relevant measurement indicators of a PHC network were delineated and described.
      Based on this, 12 design approaches of PHC concept for the GP-centered and team
      oriented primary health care in rural areas have been developed.

PMID- 27878395
TI  - A tale of two methane monooxygenases.
AB  - Methane monooxygenase (MMO) enzymes activate O2 for oxidation of methane. Two
      distinct MMOs exist in nature, a soluble form that uses a diiron active site
      (sMMO) and a membrane-bound form with a catalytic copper center (pMMO).
      Understanding the reaction mechanisms of these enzymes is of fundamental
      importance to biologists and chemists, and is also relevant to the development of
      new biocatalysts. The sMMO catalytic cycle has been elucidated in detail,
      including O2 activation intermediates and the nature of the methane-oxidizing
      species. By contrast, many aspects of pMMO catalysis remain unclear, most notably
      the nuclearity and molecular details of the copper active site. Here, we review
      the current state of knowledge for both enzymes, and consider pMMO O2 activation
      intermediates suggested by computational and synthetic studies in the context of
      existing biochemical data. Further work is needed on all fronts, with the
      ultimate goal of understanding how these two remarkable enzymes catalyze a
      reaction not readily achieved by any other metalloenzyme or biomimetic compound.

PMID- 27878398
TI  - HSP90 is a promising target in gemcitabine and 5-fluorouracil resistant
      pancreatic cancer.
AB  - Chemotherapy (CT) options in pancreatic cancer (PC) are limited to gemcitabine
      and 5-fluorouracil (5-FU). Several identified molecular targets in PC represent
      client proteins of HSP90. HSP90 is a promising target since it interferes with
      many oncogenic signaling pathways simultaneously. The aim of this study was to
      evaluate the efficacy of different HSP90 inhibitors in gemcitabine and 5-FU
      resistant PC. PC cell lines 5061, 5072 and 5156 were isolated and brought in to
      culture from patients being operated at our institution. L3.6pl cell line served
      as a control. Anti-proliferative efficacy of three different HSP90 inhibitors (17
      AAG, 17-DMAG and 17-AEPGA) was evaluated by the MTT assay. Alterations in
      signaling pathway effectors and apoptosis upon HSP90 inhibition were determined
      by western blot analysis and annexin V/PI staining. The cell lines 5061, 5072 and
      5156 were resistant to gemcitabine and 5-FU. In contrast 17-AAG and the water
      soluble derivates 17-DMAG and 17-AEPGA displayed high anti-proliferative activity
      in all tested cell lines. The calculated IC50 was below 1 uM. Highly significant
      down regulation of epidermal-growth-factor-receptor, insulin-like-growth-factor
      receptor-1, AKT and MAPK reflected the intracellular molecular signaling-network
      disruption. Furthermore, besides HSP70 also HSP27 was upregulated in all cell
      lines. Apoptosis occurred early under HSP90 inhibition and was determined by
      annexin V/PI staining and CASPASE-3 and PARP assay. In contrast, gemcitabine
      treated cells did not show any apoptosis. HSP90 inhibition disrupts multiple
      signaling cascades in gemcitabine and 5-FU resistant PC simultaneously and
      promotes cancer cell apoptosis. Watersoluble 17-DMAG is equally effective as 17
      AAG. HSP27, besides HSP70, may represent an effective response marker of
      successful HSP90 inhibition.

PMID- 27878399
TI  - Altered architecture and cell populations affect bone marrow mechanobiology in
      the osteoporotic human femur.
AB  - Age-related increases in trabecular bone porosity, as seen in osteoporosis, not
      only affect the strength and stiffness, but also potentially the
      mechanobiological response of bone. The mechanical interaction between trabecular
      bone and bone marrow is one source of mechanobiological signaling, as many cell
      populations in marrow are mechanosensitive. However, measuring the mechanics of
      this interaction is difficult, due to the length scales and geometric complexity
      of trabecular bone. In this study, a multi-scale computational scheme
      incorporating high-resolution, tissue-level, fluid-structure interaction
      simulations with discrete cell-level models was applied to characterize the
      potential effects of trabecular porosity and marrow composition on marrow
      mechanobiology in human femoral bone. First, four tissue-level models with
      different volume fractions (BV/TV) were subjected to cyclic compression to
      determine the continuum level shear stress in the marrow. The calculated stress
      was applied to three detailed models incorporating individual cells and having
      differing adipocyte fractions. At the tissue level, compression of the bone along
      its principal mechanical axis induced shear stress in the marrow ranging from 2.0
      to 5.6 Pa, which increased with bone volume fraction and strain rate. The shear
      stress was amplified at the cell level, with over 90% of non-adipocyte cells
      experiencing higher shear stress than the applied tissue-level stress. The
      maximum shear stress decreased by 20% when the adipocyte volume fraction (AVF)
      increased from 30%, as seen in young healthy marrow, to 45 or 60% AVF typically
      found in osteoporotic patients. The results suggest that increasing AVF has
      similar effects on the mechanobiological signaling in bone marrow as decreased
      volume fraction.

PMID- 27878400
TI  - Multiphoton microscopy observations of 3D elastin and collagen fiber
      microstructure changes during pressurization in aortic media.
AB  - Elastin and collagen fibers play important roles in the mechanical properties of
      aortic media. Because knowledge of local fiber structures is required for
      detailed analysis of blood vessel wall mechanics, we investigated 3D
      microstructures of elastin and collagen fibers in thoracic aortas and monitored
      changes during pressurization. Using multiphoton microscopy, autofluorescence
      images from elastin and second harmonic generation signals from collagen were
      acquired in media from rabbit thoracic aortas that were stretched biaxially to
      restore physiological dimensions. Both elastin and collagen fibers were observed
      in all longitudinal-circumferential plane images, whereas alternate bright and
      dark layers were observed along the radial direction and were recognized as
      elastic laminas (ELs) and smooth muscle-rich layers (SMLs), respectively. Elastin
      and collagen fibers are mainly oriented in the circumferential direction, and
      waviness of collagen fibers was significantly higher than that of elastin fibers.
      Collagen fibers were more undulated in longitudinal than in radial direction,
      whereas undulation of elastin fibers was equibiaxial. Changes in waviness of
      collagen fibers during pressurization were then evaluated using 2-dimensional
      fast Fourier transform in mouse aortas, and indices of waviness of collagen
      fibers decreased with increases in intraluminal pressure. These indices also
      showed that collagen fibers in SMLs became straight at lower intraluminal
      pressures than those in EL, indicating that SMLs stretched more than ELs. These
      results indicate that deformation of the aorta due to pressurization is
      complicated because of the heterogeneity of tissue layers and differences in
      elastic properties of ELs, SMLs, and surrounding collagen and elastin.

PMID- 27878401
TI  - Enterocin B3A-B3B produced by LAB collected from infant faeces: potential
      utilization in the food industry for Listeria monocytogenes biofilm management.
AB  - Enterococcus faecalis B3A-B3B produces the bacteriocin B3A-B3B with activity
      against Listeria monocytogenes, Staphylococcus aureus, methicillin-resistant
      Staphylococcus aureus (MRSA) and Clostridium perfringens, but apparently not
      against fungi or Gram-negative bacteria, except for Salmonella Newport. B3A-B3B
      enterocin has two different nucleotides but similar amino acid composition to the
      class IIb MR10A-MR10B enterocin. B3A-B3B consists of two peptides of predicted
      molecular mass of 5176.31 Da (B3A) and 5182.21 Da (B3B). Importantly, B3A-B3B
      impeded biofilm formation of the foodborne pathogen L. monocytogenes 162 grown on
      stainless steel. The antimicrobial treatment of stainless steel with nisin (1 or
      16 mg ml-1) decreased the cell numbers by about 2 log CFU ml-1, thereby impeding
      the biofilm formation by L. monocytogenes 162 or its nisin-resistant derivative
      strain L. monocytogenes 162R. Furthermore, the combination of nisin and B3A-B3B
      enterocin reduced the MIC required to inhibit this pathogen grown in planktonic
      or biofilm cultures.

PMID- 27878402
TI  - Impact of serum uric acid, albumin and their interaction on Parkinson's disease.
AB  - The study aimed to investigate the correlation between Parkinson's disease (PD)
      and serum levels of uric acid (UA), albumin and their interaction. A cross
      sectional study was conducted to evaluate the relationship of serum UA, albumin
      with PD. A total of 96 PD patients and 108 healthy controls were recruited at
      Huai'an First People's Hospital, Nanjing Medical University. Baseline data
      included age, gender, body mass index (BMI), disease duration, Hoehn and Yahr
      scale (H&Y) stage, serum UA and albumin levels. The levels of serum UA and
      albumin were significantly lower in PD patients than those in controls (P =
      0.001; P = 0.000). Serum albumin levels were strikingly different in H&Y group (P
      = 0.004). Multivariable logistic regression showed that the levels of serum UA (P
      = 0.001, adjusted OR 0.993, 95% CI 0.988-0.997) and albumin (P = 0.000, adjusted
      OR 0.513, 95% CI 0.425-0.620) were independent risk factors in PD. The receiver
      operating characteristic (ROC) curve analyses showed that the area under curve
      (AUC) for serum UA and albumin was 0.669 (95% CI 0.594-0.744) and 0.883 (95% CI
      0.835-0.931), respectively. The combination of serum albumin and UA improved the
      AUC to 0.898 (95% CI 0.854-0.942). Serum UA and albumin levels significantly
      decreased in PD patients and were independent risk factors for PD. More studies
      are needed to confirm our findings.

PMID- 27878403
TI  - Lutein protects against beta-amyloid peptide-induced oxidative stress in
      cerebrovascular endothelial cells through modulation of Nrf-2 and NF-kappab.
AB  - In the present study, we determined the protective role of lutein against Abeta
      25-35 peptide-induced oxidative stress and apoptosis in bEND.3 cells. Cell
      viability was determined through MTT assay. Reactive oxygen species, lipid
      peroxides, and antioxidant enzyme activities were evaluated to analyze the
      oxidative stress status. NF-kappaB and Nrf-2 downstream target protein
      expressions were determined through western blot. Apoptosis was analyzed through
      caspase activities and subG1 accumulation. The results showed that Abeta 25-35
      significantly increased (p < 0.001) oxidative stress biomarkers. Abeta 25-35
      significantly up-regulated NF-kappaB nuclear expression and down-regulated Nrf-2
      levels and HO-1 and, NQO-1 expressions. Abeta 25-35 induced apoptosis through
      decreasing mitochondrial membrane potential and increasing caspase 9 and 3
      activities. Lutein pre-treatment significantly (p < 0.001) improved cell
      viability and decreased ROS levels (p < 0.001) and lipid peroxidation (p < 0.01).
      Lutein prevented Abeta 25-35-induced NF-kappaB nuclear expressions and up
      regulated Nrf-2 expressions. Further, lutein also improved mitochondrial membrane
      potential and down-regulated caspase activities and subG1 accumulation. The
      present study shows the protective role of lutein against Abeta 25-35-induced
      toxicity by modulating Nrf-2 and NF-kappaB expressions in cerebrovascular
      endothelial cells.

PMID- 27878404
TI  - Inter-rater agreement between trained emergency medicine residents and
      radiologists in the examination of gallbladder and common bile duct by
      ultrasonography.
AB  - STUDY OBJECTIVES: Bedside emergency ultrasonograAmerican Society of Emergency
      Radiologyphy is a rapid diagnostic tool in the emergency department (ED).
      Nevertheless, the learning curve for ultrasound (US) training in various
      indications has to date not been clearly defined. The aim of the present study
      was to assess how much a short specialized training program in hepatobiliary US
      might impact the skills of novice emergency medicine residents. METHODS: This was
      a prospective observational study conducted at a university-affiliated ED from
      May 2014 to January 2015. Adult patients who had right upper quadrant (RUQ)
      abdominal pain were included. Prior to enrolling patients, seven residents
      voluntarily passed a 10-h hepatobiliary US training course; they also carried out
      20 hands-on US examinations. To compare the results, three board-certified
      radiologists performed another US examination blindly. The degree of agreement
      between the two groups was calculated. RESULTS: A total of 200 individuals
      enrolled, among whom 106 (53%) were males and 53 (47%) were females. Mean +/- SD
      age was 50.21 +/- 22.06 years. There was a moderate to perfect level of agreement
      between emergency medicine residents and radiologists in terms of the presence of
      a gallstone (Cohen's kappa = 0.85), sonographic Murphy sign (Cohen's kappa =
      0.95), gallbladder wall thickening (Cohen kappa = 0.75), and common bile duct
      (CBD) dilation (Cohen's kappa = 0.79). CONCLUSION: Novice emergency medicine
      residents attained a moderate to perfect degree of agreement with expert
      radiologists in detecting gallstone presence, thick gallbladder wall, sonographic
      Murphy sign, and CBD dilation in standard patients, after participating in a
      specific US course.

PMID- 27878405
TI  - A comparison study between 3D T2-weighted SPACE and conventional 2D T2-weighted
      turbo spin echo in assessment of carotid plaque.
AB  - The aim of this study was to compare 3D T2-weighted sampling perfection with
      application optimized contrast using different flip angle evolutions (T2w SPACE)
      with conventional 2D T2w turbo-spin echo (TSE) in plaque imaging of carotid
      artery. 45 patients underwent 3.0-T MRI for carotid arteries imaging. MR
      sequences included T2w SPACE, T2w TSE, Time of flight (TOF) and T1-weighted (T1w)
      TSE. The signal intensity of intra-plaque hemorrhage (IPH), lipid-rich necrotic
      core (LRNC), and loose matrix (LM) were measured and their contrast ratios (CRs)
      against adjacent muscle were calculated. CRs from T2w SPACE and T2w TSE were
      compared to each other. CRs of LM, LRNC, and IPH measured on T2w SPACE were 1.74
      3.04 (2.44), 0.98-1.66 (1.39), and 1.91-2.93 (2.51), respectively. CRs of LM,
      LRNC, and IPH on T2w TSE were 1.97-3.41 (2.44), 1.18-1.73 (1.43), and 2.26-3.75
      (2.26), respectively. There was no significant difference of CR of the carotid
      plaques between T2w SPACE and T2w TSE (p = 0.455). Markedly significant
      differences of CRs were found between LM and LRNC (p < 0.001), and between LRNC
      and IPH (p < 0.001) on T2w SPACE and T2w TSE. T2w SPACE was comparable with
      conventional T2w TSE in characterization of carotid plaque.

PMID- 27878406
TI  - Diagnostic value of layer-specific global longitudinal strain during adenosine
      stress in patients suspected of coronary artery disease.
AB  - Speckle tracking global longitudinal strain (GLS) from dobutamine stress
      echocardiography (SE) predicts coronary artery disease (CAD). The diagnostic
      value of GLS from vasodilator SE and the additional value of layer-specific
      speckle tracking analysis are unclear. We explored the usefulness of layer
      specific GLS and non-layer-specific strain (automated functional imaging, AFI)
      from adenosine SE. The included 132 patients (67% male, 62.6 (9.0) years), of
      which 46 (35%) had CAD defined as >=1 stenosis >=70% (>=50% in the left main),
      underwent adenosine SE and invasive coronary angiography. Resting AFI and layer
      specific GLS were similar in patients with or without CAD (p > 0.05). The stress
      rest difference (Deltavalue = stress-value - rest-value) in patients with CAD was
      less pronounced compared to patients without proved CAD (Deltaendocardial GLS: 
      1.2 (3.5)% vs. -5.0 (3.2)%; Deltamidventricular GLS: -0.95 (3.0)% vs. -4.2
      (2.7)%; Deltaepicardial GLS: -0.7 (2.5)% vs. -3.4 (2.3)%; DeltaAFI: -0.8 (2.9)%
      vs. -3.6 (3.1)%, p < 0.00001 for all comparisons). The diagnostic value of the
      three layer-specific GLS values and AFI were statistically similar (p = 0.19).
      The four Deltavalues provided independent predictive value to the risk assessment
      given by gender, age, wall motion and DeltaEF (p = 0.002, AFI and p < 0.0001,
      layer-specific GLS). The accuracies were acceptable (71-80%) with modest
      sensitivities (54-65%) and high specificities (80-91%). The deformation response
      to vasodilator infusion was associated with the presence of CAD. Endocardial,
      midventricular and epicardial GLS and AFI from adenosine SE had similar
      diagnostic values. The specificities were high, but the modest sensitivities are
      a limitation to the clinical application.

PMID- 27878407
TI  - Low serum fibroblast growth factor 2 levels not accompanied by increased serum
      pentraxin 3 levels in patients with systemic sclerosis.
AB  - There are scarce clinical data regarding serum pentraxin 3 (PTX3) and fibroblast
      growth factor 2 (FGF2) in patients with systemic sclerosis (SSc). Study was
      conducted to evaluate serum levels in our SSc cohort. Serum PTX3 and FGF2
      concentrations were compared among SSc, disease control (systemic lupus
      erythematosus (SLE)), and healthy control groups. We also examined the
      association of serum levels of PTX3 and FGF2 with disease manifestations. Serum
      PTX3 levels were similarly distributed among SSc (n = 93) and healthy groups (n =
      66) (p = 1.00) while PTX3 levels were higher in SLE controls (n = 86) compared to
      both SSc and healthy groups. PTX3 levels were higher in limited SSc cases
      compared to diffuse cases (p = 0.016). Median PTX3 levels in SSc cases with lung
      involvement were lower compared to cases with no lung involvement (p = 0.006).
      Patients with SSc had significantly lower serum levels of FGF2 compared to SLE
      and healthy groups. Serum FGF2 concentration was undetectable in 61.3% of cases
      with SSc while 30.2% of SLE and only 4.5% of healthy cases had undetectable FGF2
      levels (p < 0.01). Diffuse and limited SSc cases, as well as cases with and
      without lung involvement, had similar rates of undetectable serum FGF2 levels (p
      = 0.15 and p = 0.59, respectively). FGF2 levels were mostly undetectably low in
      patients with SSc, and serum PTX3 was lower in diffuse SSc and in cases with lung
      involvement compared to limited SSc and cases with no lung involvement,
      respectively, in our cohort.

PMID- 27878408
TI  - Rheumatologists' perception of systemic lupus erythematosus quality indicators:
      significant interest and perceived barriers.
AB  - Differences in quality of care may contribute to health disparities in systemic
      lupus erythematosus (SLE). Studies show low physician adherence rates to the SLE
      quality indicators but do not assess physician perception of SLE quality
      indicators or quality improvement. Using a cross-sectional survey of
      rheumatologists in the southeastern USA, we assessed the perception and
      involvement of rheumatologists in quality improvement and the SLE quality
      indicators. Using electronic mail, an online survey of 32 questions was delivered
      to 568 rheumatologists. With a response rate of 19% (n = 106), the majority of
      participants were male, Caucasian, with over 20 years of experience, and seeing
      adult patients in an academic setting. Participants had a positive perception
      toward quality improvement (81%) with a majority responding that the SLE quality
      indicators would significantly impact quality of care (54%). While 66% of
      respondents were familiar with the SLE quality indicators, only 18% of
      respondents reported using them in everyday practice. The most commonly reported
      barrier to involvement in quality improvement and the SLE quality indicators was
      time. Rheumatologists had a positive perception of the SLE quality indicators and
      agreed that use of the quality indicators could improve quality of care in SLE;
      however, they identified time as a barrier to implementation. Future studies
      should investigate methods to increase use of the SLE quality indicators.

PMID- 27878409
TI  - Analysis of the functional muscle-bone unit of the forearm in patients with
      phenylketonuria by peripheral quantitative computed tomography.
AB  - Bone disease in patients with phenylketonuria (PKU) is incompletely
      characterized. We therefore analyzed, in a cross-sectional study radius
      macroscopic bone architecture and forearm muscle size by peripheral quantitative
      computed tomography (pQCT) and muscle strength by hand dynamometry in a large
      cohort (n = 56) of adolescent and adult patients with PKU aged 26.0 +/- 8.9
      (range, 11.8-41.5) years. Data were compared with a reference population (n =
      700) from the DONALD study using identical methodology. We observed a significant
      reduction of cortical thickness (z-score -1.01 +/- 0.79), Strength-Strain Index
      (SSI) (z-score -0.81 +/- 1.03), and total bone mineral density (BMD) of the
      distal radius (z-score -1.05 +/- 1.00). Mean muscle cross-sectional area (z-score
      -0.98 +/- 1.19) and muscle grip force (z-score -0.64 +/- 1.26) were also
      significantly reduced, indicating an impaired muscular system as part of the
      clinical phenotype of PKU. SSI positively correlated (r = 0.53, P < 0.001) with
      the corresponding muscle cross-sectional area in the reference population;
      however, the regression line slope in PKU patients was less steep (P < 0.001),
      indicating that bone strength is not adequately adapted to muscle force. In
      conclusion, the radial bone in PKU patients is characterized by reduced bone
      strength in relation to muscular force, decreased cortical thickness, and
      impaired total BMD at the metaphyseal site. These alterations indicate a mixed
      bone defect in PKU, both of which are due to primary alterations of bone
      metabolism and to secondary alterations in response to neuromuscular
      abnormalities.

PMID- 27878410
TI  - The Sexual Orientation and Gender Presentation of Hijra, Kothi, and Panthi in
      Mumbai, India.
AB  - Cultural categories related to sexuality and gender vary considerably cross
      culturally. While Western cultures categorize people primarily in terms of sexual
      attractions (i.e., gay, straight, bisexual), many cultures distinguish between
      groups based on additional issues such as gender role presentation and position
      preference in anal sex (i.e., insertive/receptive). The current study gathered
      data on three categories of natal males in Mumbai, India-hijra, kothi, and panthi
      (N = 93). Hijra are androphilic (sexually attracted to adult men), typically
      sexually receptive, transgender, sometimes castrated, and live in fictive kinship
      networks that are hierarchically organized. Kothi are also androphilic, typically
      sexual receptive and relatively feminine but less so than hijra; unlike hijra,
      kothi are never castrated. Hijra and kothi were understood by some participants
      to be mutually compatible, and so three groups were identified-those endorsing
      hijra only (n = 11), kothi only (n = 22), and both hijra and kothi (n = 22).
      Panthi (n = 38) are the masculine insertive partners of hijra and kothi. Measures
      employed were self-report and viewing time measures of sexual attraction, sexual
      behavior and position preference, self-described masculinity/femininity, recalled
      childhood gender atypicality, gendered occupational preferences, and gender
      presentation milestones (i.e., wearing female clothes, castration). All hijra and
      kothi groups were found to be exclusively androphilic in viewing time and self
      reported sexual attractions, and to be gender-atypical on all measures. Panthi
      were found to be relatively male-typical and to have a bisexual pattern of
      viewing time and self-reported sexual attractions. Kothi were found to be less
      extreme in their female typicality and to report less female gender presentation
      milestones than hijra or hijra/kothi. Most hijra and hijra/kothi and all kothi
      said that they were not castrated. Contrary to the manner in which they are
      socially defined, a third of panthi report having been receptive in anal sex, and
      a third of all hijra and kothi groups report having been insertive at some time.

PMID- 27878413
TI  - Does the General Strain Theory Explain Gambling and Substance Use?
AB  - General Strain Theory (GST: Agnew Criminology 30:47-87, 1992) posits that deviant
      behaviour results from adaptation to strain and the consequent negative emotions.
      Empirical research on GST has mainly focused on aggressive behaviours, while only
      few research studies have considered alternative manifestations of deviance, like
      substance use and gambling. The aim of the present study is to test the ability
      of GST to explain gambling behaviours and substance use. Also, the role of family
      in promoting the adoption of gambling and substance use as coping strategies was
      verified. Data from 266 families with in mean 8 observations for each group were
      collected. The multilevel nature of the data was verified before appropriate
      model construction. The clustered nature of gambling data was analysed by a two
      level Hierarchical Linear Model while substance use was analysed by Multivariate
      Linear Model. Results confirmed the effect of strain on gambling and substance
      use while the positive effect of depressive emotions on these behaviours was not
      supported. Also, the impact of family on the individual tendency to engage in
      addictive behaviours was confirmed only for gambling.

PMID- 27878412
TI  - Effect of uphill and downhill walking on walking performance in geriatric
      patients using a wheeled walker.
AB  - BACKGROUND: Wheeled walkers are recommended to improve walking performance in
      older persons and to encourage and assist participation in daily life.
      Nevertheless, using a wheeled walker can cause serious problems in the natural
      environment. This study aimed to compare uphill and downhill walking with walking
      level in geriatric patients using a wheeled walker. Furthermore, we investigated
      the effect of using a wheeled walker with respect to dual tasking when walking
      level. METHODS: A total of 20 geriatric patients (median age 84.5 years) walked
      10 m at their habitual pace along a level surface, uphill and downhill, with and
      without a standard wheeled walker. Gait speed, stride length and cadence were
      assessed by wearable sensors and the walk ratio was calculated. RESULTS: When
      using a wheeled walker while walking level the walk ratio improved (0.58
      m/[steps/min] versus 0.57 m/[steps/min], p = 0.023) but gait speed decreased
      (1.07 m/s versus 1.12 m/s, p = 0.020) when compared to not using a wheeled
      walker. With respect to the walk ratio, uphill and downhill walking with a
      wheeled walker decreased walking performance when compared to level walking (0.54
      m/[steps/min] versus 0.58 m/[steps/min], p = 0.023 and 0.55 m/[steps/min] versus
      0.58 m/[steps/min], p = 0.001, respectively). At the same time, gait speed
      decreased (0.079 m/s versus 1.07 m/s, p < 0.0001) or was unaffected. CONCLUSION:
      The use of a wheeled walker improved the quality of level walking but the
      performance of uphill and downhill walking was worse compared to walking level
      when using a wheeled walker.

PMID- 27878411
TI  - Reckless administration of QT interval-prolonging agents in elderly patients with
      drug-induced torsade de pointes.
AB  - A systematic review was conducted for all published case reports on drug-induced
      torsade de pointes (TdP) in elderly (>=80 years) patients to study if the
      administration of the offending agent was reckless. Overall, 61 reports on drug
      induced TdP in patients aged 80-97 years were included in the analysis. Non
      modifiable risk factors for drug-induced TdP (e.g. acute coronary syndrome,
      female gender and congestive heart failure), modifiable risk factors (e.g.
      hypokalemia, severe hypomagnesemia and digitalis toxicity) and reckless
      administration of a QT interval-prolonging agent (e.g. despite a known QT
      interval prolongation or a history of TdP, together with other QT interval
      prolonging agents in higher than recommended doses) were recorded in each case.
      Overall, 54 (88.5%) patients had non-modifiable risk factors for drug-induced TdP
      and 21 (34.4%) patients had modifiable risk factors. The administration of the
      offending agent was reckless in one half (n = 31; 50.8%) of the patients. The
      most prevalent reckless administration of a QT interval-prolonging agent was
      together with other QT interval-prolonging agents (n = 16; 51.6%) or despite QT
      interval prolongation (n = 8; 25.8%). In conclusion, although risk factors for
      drug-induced TdP are prevalent in elderly patients with drug-induced TdP, in
      approximately 50% of patients it appeared following a reckless administration of
      a QT interval-prolonging agent. In this population physicians should particularly
      avoid administration of two or more QT interval-prolonging agents simultaneously
      or administration of a QT interval-prolonging agent despite QT interval
      prolongation.

PMID- 27878414
TI  - A Creation Narrative for the Psychometric Society and Psychometrika: In the
      Beginning There Was Paul Horst.
AB  - A review is provided for the creation of the Psychometric Society in 1935, and
      the establishment of its journal, Psychometrika, in 1936. This document is part
      of the 80th anniversary celebration for Psychometrika's founding, held during the
      annual meeting of the Psychometric Society in July of 2016 in Asheville, NC.

PMID- 27878415
TI  - Direct and Indirect Effects of Maltreatment and Social Support on Children's
      Social Competence Across Reporters.
AB  - Children's social competence is a key characteristic of resilience, yet little
      research has assessed contributing factors to this construct. The objectives of
      this study were to examine direct and indirect effects of maltreatment on
      children's social competence, the promotive role of child and caregiver social
      support, and factors contributing to reports of child social competence across
      informants. Structural equation modeling evaluated the influence of CPS report
      history, child adjustment, and child and caregiver social support on child social
      competence in n = 783 caregiver-child dyads. CPS report history (age 0-8) was
      indirectly related to low social competence through child adjustment problems.
      Social support was a significant promotive factor of child social competence,
      with caregiver social supports predicting higher levels of parent-reported child
      social competence. Child social support predicted self-reported child social
      competence. Findings reinforce the assertion that both caregiver and child social
      support networks are critical to promoting child well-being after adversity.

PMID- 27878416
TI  - Identification of large variation in the photosynthetic induction response among
      37 soybean [Glycine max (L.) Merr.] genotypes that is not correlated with steady
      state photosynthetic capacity.
AB  - Irradiance continuously fluctuates during the day in the field. The speed of the
      induction response of photosynthesis in high light affects the cumulative carbon
      gain of the plant and could impact growth and yield. The photosynthetic induction
      response and its relationship with the photosynthetic capacity under steady-state
      conditions (P max) were evaluated in 37 diverse soybean [Glycine max (L.) Merr.]
      genotypes. The induction response of leaf photosynthesis showed large variation
      among the soybean genotypes. After 5 min illumination with strong light, genotype
      NAM23 had the highest leaf photosynthetic rate of 33.8 umol CO2 m-2 s-1, while
      genotype NAM12 showed the lowest rate at 4.7 umol CO2 m-2 s-1. Cumulative CO2
      fixation (CCF) during the first 5 min of high light exposure ranged from 5.5 mmol
      CO2 m-2 for NAM23 to 0.81 mmol CO2 m-2 for NAM12. The difference in the induction
      response among genotypes was consistent throughout the growth season. However,
      there was no significant correlation between CCF and P max among genotypes
      suggesting that different mechanisms regulate P max and the induction response.
      The observed variation in the induction response was mainly attributed to
      ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) activation, but soybean
      lines differing in the induction response did not differ in the leaf content of
      Rubisco activase alpha- and beta-proteins. Future studies will be focused on
      identifying molecular determinants of the photosynthetic induction response and
      determining whether this trait could be an important breeding target to achieve
      improved growth of soybeans in the field.

PMID- 27878418
TI  - Factors Associated With Current Smoking Among Off-Reserve First Nations and Metis
      Youth: Results From the 2012 Aboriginal Peoples Survey.
AB  - First Nations and Metis, two of Canada's constitutionally recognized Indigenous
      groups, suffer from poorer overall health than non-Indigenous Canadians. Current
      smoking, a known predictor of chronic health conditions, is close to twice as
      prevalent among Indigenous youth as it is among non-Indigenous Canadian youth.
      However, little population-level research has examined the correlates of current
      smoking among this population. Guided by a health framework centered on
      Indigenous-specific determinants, we used data from the 2012 Aboriginal Peoples
      Survey to examine the correlates of current smoking among First Nations and Metis
      youth aged 15-17 years living outside of First Nations reserves. Using binary
      logistic regression, we investigated how culturally specific factors, namely
      knowledge of an Indigenous language, participation in traditional activities, and
      family members' attendance at residential schools, were correlated with current
      smoking. We also considered demographic, geographic, socioeconomic and health
      related correlates. Overall, an estimated 20.6% of First Nations and Metis youth
      reported current smoking. We found no significant associations between culturally
      specific activities and current smoking in the multivariate analyses, although
      those who spoke an Indigenous language were more likely to smoke. Those who
      participated in sports more often were less likely to smoke, and respondents who
      reported heavy drinking and who were from families with lower income were more
      likely to smoke. Gender, body mass index, urban/rural geography and regional
      geography, and mother's highest level of education were not significantly
      correlated with smoking. The results of our study support prior research that has
      found a disturbingly high prevalence of current smoking among Indigenous youth,
      compared to their non-Indigenous counterparts. Our results highlight the
      importance of considering sports participation, co-occurring health-risk
      behaviours and socioeconomic factors when developing interventions aimed at
      reducing the prevalence of smoking among First Nations and Metis youth.

PMID- 27878417
TI  - Neurobehavioural evaluation of resveratrol in murine models of anxiety and
      schizophrenia.
AB  - Resveratrol, a caloric restriction mimetic, is a naturally occurring polyphenolic
      compound with antioxidant and anti-inflammatory properties. Oxidative stress has
      been implicated in the etiology of a number of neuropsychiatric disorders
      including generalized anxiety and schizophrenia. This study investigated the
      anxiolytic and antipsychotic potentials of resveratrol in murine models of
      anxiety and schizophrenia. Mice were pretreated with resveratrol (200 and 400
      mg/kg) in 1% carboxymethyl cellulose for 14 days and subjected to behavioural
      tests on the 15th day. Anxiolytic activity of resveratrol was determined using
      the hole board and staircase tests while its anti-psychotic property was
      evaluated via apormorphine induced stereotypy and swim-induced grooming tests.
      Although resveratrol did not significantly reduce the mean number of head dips at
      doses used in the hole board test, it significantly (p < 0.01) decreased the mean
      episodes of rearing without significantly altering the total number of upward
      steps climbed in the staircase test. Resveratrol significantly (p < 0.05) reduced
      the mean climbing scores in the first ten minutes of the apormorphine induced
      stereotypic climbing and significantly decreased (p < 0.01) episodes and total
      duration of swim induced grooming in mice. Administration of resveratrol at doses
      used in this study produced anxiolysis and anti-psychotic effects in mice.

PMID- 27878420
TI  - A 5-year clinical follow-up after duty-cycled phased RF ablation of paroxysmal
      atrial fibrillation.
AB  - PURPOSE: Catheter radiofrequency ablation (RFA) is an effective treatment for
      symptomatic paroxysmal atrial fibrillation (AF). It has been demonstrated that
      the multielectrode pulmonary vein ablation catheter (PVAC) has favourable
      outcomes at 6-12 months post-ablation, but there are only few studies with a long
      term follow-up. METHODS: We retrospectively reviewed 77 consecutive PVAC
      procedures in our centre, from November 2007 to December 2012. RFA was attempted
      in patients with symptomatic paroxysmal AF (mean age 58.7 +/- 9.8 years, 50 men
      (64.9 %). The ablation strategy consisted of circumferential pulmonary vein
      isolation (CPVI) with the PVAC system. A questionnaire was used over the follow
      up period to assess the efficacy of AF ablation. Success was defined as freedom
      from AF/atrial flutter or atrial arrhythmia for a period ranging from 3 to 12
      months or more. RESULTS: Seventy-seven patients were included with paroxysmal AF.
      The mean duration of the procedure was 99.6 +/- 26 min and fluoroscopy time 19.4
      +/- 6.8 min. Time of RFA was 22.4 +/- 5.8 min. Acute complication rate was 10.4 %
      (the most frequent was vascular injury for 6 patients 7.8 %, 1 patient presented
      sepsis (1.3 %), 1 patient presented transient ischemic stroke). After a single
      procedure at a mean FU of 55 +/- 11 months, 54/77 (70.1 %) patients were free of
      symptomatic AF. CONCLUSIONS: These long-term results suggest that PVAC is an
      efficient system for CPVI of symptomatic paroxysmal AF.

PMID- 27878419
TI  - Split renal function of both kidneys after robot-assisted partial nephrectomy for
      renal tumor larger than 4 cm.
AB  - PURPOSE: Relative few studies reported the changes in split renal function using
      renal scintigraphy for robot-assisted partial nephrectomy (RaPN) for renal tumor
      >4 cm. This study aimed at demonstrating that RaPN is safe for renal tumor >4 cm
      without damaging the renal function of ipsilateral and contralateral kidney.
      METHODS: Patients who underwent RaPN for single renal tumor from December 2009 to
      December 2013 were identified from a prospectively collected database. We
      compared demographic, perioperative, and postoperative outcomes between patients
      with renal tumor >4 cm (case group) and patients with renal tumor ?4 cm (control
      group). Renal function was assessed by serum creatinine, estimated glomerular
      filtration rate, and effective renal plasma flow (ERPF). RESULTS: One hundred and
      three consecutive patients (45 in case group and 58 in control group) were
      identified. Case group had significantly longer operative time (P = 0.011),
      longer warm ischemia time (P < 0.001), and more estimated blood loss (P = 0.010)
      than control group. Only one patient in the case group had conversion surgery.
      There was no significant difference regarding hospital stay, blood transfusion,
      complications rate, and positive surgical margin. The changes in ipsilateral ERPF
      and contralateral ERPF were not significantly different between groups
      (ipsilateral kidney: -10.5 vs. -12.5%, P = 0.989; contralateral kidney: -3.6 vs. 
      5.2%, P = 0.611). CONCLUSIONS: RaPN is a safe and feasible modality of nephron
      sparing surgery for renal tumor >4 cm, as it is for renal tumor ?4 cm.

PMID- 27878422
TI  - The Recovery of Beta-Cell Function is Critical for Antidiabetic Outcomes of
      Gastric Bypass in Asian Subjects with Type 2 Diabetes and a Body Mass Index Below
      30.
AB  - Type 2 diabetes (T2D) in Asian populations is characterized by a lower body mass
      index (BMI) than in Caucasian cases. This pilot study investigated antidiabetic
      outcomes after a Roux-en-Y gastric bypass (RYGB) in Asian subjects with T2D and
      BMI < 30. Fifteen Koreans with poorly controlled T2D and BMI 23-30 underwent
      RYGB. Two years after RYGB, seven patients achieved HbA1c < 6.5% without
      medication (target-achieved). The other cases also showed improved glycemic
      control. The insulin secretory response during an oral glucose tolerance test was
      significantly restored in the target-achieved group. Postoperative changes in
      insulin sensitivity and body weight did not differ between these groups. Beta
      cell function improvement is an important determinant of the long-term
      antidiabetic outcomes of RYGB in Asian subjects with BMI < 30.

PMID- 27878421
TI  - The role of the atrial electromechanical delay in predicting atrial fibrillation
      in beta-thalassemia major patients.
AB  - BACKGROUND: Paroxysmal atrial tachyarrhythmias frequently occur in beta
      thalassemia major (beta-TM) patients. The aim of the current study was to
      evaluate the atrial electromechanical delay (AEMD) in a large beta-TM population
      with normal cardiac function and its relationship to atrial fibrillation (AF)
      onset. METHODS: Eighty beta-TM patients (44 men, 36 women), with a mean age of
      36.2 +/- 11.1 years, and 80 healthy subjects used as controls, matched for age
      and gender, were studied for the occurrence of AF during a 5-year follow-up,
      through 30-day external loop recorder (ELR) monitoring performed every 6 months.
      Intra-AEMD and inter-AEMD of both atria were measured through tissue Doppler
      echocardiography. P-wave dispersion (PD) was carefully measured using 12-lead
      electrocardiogram (ECG). RESULTS: Compared to the healthy control group, the beta
      TM patients showed a statistically significant increase in inter-AEMD, intra-left
      AEMD, maximum P-wave duration, and PD. Dividing the beta-TM group into two
      subgroups (patients with or without AF), the inter-AEMD, intra-left AEMD, maximum
      P-wave duration, and PD were significantly higher in the subgroup with AF
      compared to the subgroup without AF. There were significant good correlations of
      intra-left AEMD and inter-AEMD with PD. A cut-off value of 40.1 ms for intra-left
      AEMD had a sensitivity of 76.2% and a specificity of 97.5% in identifying beta-TM
      patients with AF risk. A cut-off value of 44.8 ms for inter-AEMD had a
      sensitivity of 81.2% and a specificity of 98.7% in identifying this category of
      patients. CONCLUSIONS: Our results showed that the echocardiographic atrial
      electromechanical delay indices (intra-left and inter-AEMD) and the PD were
      significantly increased in beta-TM subjects with normal cardiac function. PD and
      AEMD represent non-invasive, inexpensive, useful, and simple parameters to assess
      the AF risk in beta-TM patients.

PMID- 27878423
TI  - Gastrointestinal Quality of Life Improves Significantly After Sleeve Gastrectomy
      and Roux-en-Y Gastric Bypass-a Prospective Cross-Sectional Study Within a 2-Year
      Follow-up.
AB  - INTRODUCTION: Morbidly obese patients have lower quality of life (QOL) when
      compared to the general population. So far, no studies have compared gender and
      procedural differences in gastrointestinal QOL after sleeve gastrectomy (SG) and
      Roux-en-Y gastric bypass (RYGB). METHODS: Patients before and after bariatric
      surgery completed the gastrointestinal quality of life index (GIQLI), a 36-item
      questionnaire with five subscores. Differences between SG and RYGB were analyzed,
      as were gender differences. RESULTS: Some 186 patients completed the
      questionnaire, 75 before surgery, 56 within 6 months, and 55 within 24 months
      after surgery. Total GIQLI score and all subscores were significantly better
      within 24 months after surgery (80.9 +/- 19.2 vs. 109.2 +/- 17.7, p < 0.001). The
      specific gastrointestinal items 'feeling of fullness', 'eating pleasure', 'slow
      speed of eating', and 'diarrhea' were also significantly better after surgery
      whereas many other gastrointestinal items were not different. Total GIQLI score
      was significantly higher for SG than for RYGB within 6 months, while there were
      no significant differences within 24 months after surgery. There were also no
      significant differences in specific gastrointestinal items between SG and RYGB
      within 24 months after surgery and in total GIQLI score between female and male
      patients. CONCLUSION: Total GIQLI score and all subscores were higher within 24
      months after bariatric surgery. Total GIQLI score was significantly higher after
      SG when compared to RYGB within 6 months, but not different within 24 months
      after surgery. There was no difference in total GIQLI score between female and
      male patients.

PMID- 27878424
TI  - Intragastric Balloon for Management of Severe Obesity: Letter to the Editor.

PMID- 27878425
TI  - The Role of Routine Upper Gastrointestinal Endoscopy Before Bariatric Surgery
      (Response to Letter).

PMID- 27878427
TI  - Development of the forensic inpatient quality of life questionnaire: short
      version (FQL-SV).
AB  - PURPOSE: Aim of this study was to develop a brief version of the Forensic
      inpatient Quality of Life questionnaire (FQL). METHODS: Data from a longitudinal
      study of quality of life (QoL) among long-term forensic psychiatric care (LFPC)
      patients (N = 130) were used. Per domain, the FQL item that correlated most
      highly with the mean domain score and Overall QoL was selected. Internal
      consistency was investigated by calculating Cronbach's alpha. Construct validity
      was examined by investigating the relationship with the WHOQOL-Bref and EssenCES.
      RESULTS: The original division into 15 QoL domains was retained, while the number
      of items per domain was reduced to one or two. The amount of subjective items was
      shortened from 114 items to 19 items. Reliability analysis demonstrated good
      internal consistency (Cronbach's alpha = .79). Content validity was assured
      because the FQL-SV is based on the items of the original FQL that was derived
      from LFPC patient's and staff's opinions. Construct validity was demonstrated.
      CONCLUSIONS: This study has shown that the FQL-SV is a psychometrically valid
      abbreviation of the FQL and can therefore be used to monitor or assess QoL in
      forensic psychiatric care. However, when certain domains should be targeted in
      treatment, the FQL (full version) can assist both the patient and the clinician
      to get a more complete view of the individualized targets they should be aiming
      at in order to improve QoL.

PMID- 27878426
TI  - The Differential Effects of Alzheimer's Disease and Lewy Body Pathology on
      Cognitive Performance: a Meta-analysis.
AB  - Differential diagnosis of Alzheimer's disease (AD) from normal aging and other
      dementia etiologies is imperative for disease specific treatment options and long
      term care planning. Neuropathological confirmation is the gold standard for
      neurodegenerative disease diagnosis, yet most published studies examining the use
      of neuropsychological tests in the differential diagnosis of dementia rely upon
      clinical diagnostic outcomes. The present study undertook a meta-analytic review
      of the literature to identify cognitive tests and domains that allow for the
      differentiation of individuals with AD pathology from individuals with dementia
      with Lewy Bodies (DLB) pathology and pathology-free individuals. A comprehensive
      literature search yielded 14 studies that met the inclusion criteria for the
      present meta-analysis. Six studies comprised 222 decedents with AD compared to
      433 normal controls, and eight studies comprised 431 cases of AD compared to 155
      decedents with DLB. Results revealed that the effect of having
      neuropathologically confirmed AD versus DLB lowered performance in the memory
      domain, and having DLB decreased performance in the visuospatial domain. No
      single test differed significantly across the AD and DLB groups. For the AD and
      pathology free comparison, results indicated that that AD was associated with
      poorer performance on the memory and language domains. With respect to specific
      cognitive tests, AD produced lower scores on list learning tests, category
      fluency, and the Digit Symbol substitution test. The limited number of studies
      meeting inclusion criteria warrants formulation of guidelines for reporting in
      clinico-pathological studies; suggested guidelines are provided.

PMID- 27878428
TI  - Seroprevalence of Anaplasma marginale and Babesia bigemina infections and
      associated risk factors in Machakos County, Kenya.
AB  - Anaplasma marginale and Babesia bigemina are important tick-borne pathogens of
      cattle. A cross-sectional survey was undertaken to determine the seroprevalence
      of A. marginale and B. bigemina infections and identify associated risk factors
      on traditional smallholder farms in Machakos County, Kenya. A total of 421 cattle
      from 127 farms from four divisions in the county were sampled and visited between
      September and November 2007. The farms were selected by a proportional allocation
      approach based on the number of farms in the four divisions previously selected
      by stratified random sampling method. Information on animal and individual farm
      management variables was obtained using standardized questionnaires. Prevalence
      of serum antibodies due to A. marginale and B. bigemina pathogens was determined
      using the enzyme-linked immunosorbent assay (ELISA) technique. The relationship
      between the seropositivity and associated risk factors was assessed by
      multivariable analyses using standard logistic regression models. The overall
      estimation (and their 95% confidence intervals) of A. marginale and B. bigemina
      seropositivity at the animal level was 53.4% (48.5%, 58.2%) and 40.6% (35.8%,
      45.4%), respectively. Two variables, "animal age" and "administrative division,"
      were significantly associated with the A. marginale seroresponse. Three
      variables, "animal age" "grazing system" and "administrative division" were
      significantly associated with the B. bigemina seroresponse. These findings
      suggest possible indicators of existence of endemic instability for the two
      infections. The study identifies characterization of environmental suitability
      for the vectors and how they interact with grazing systems to cause the
      infections as an area for further studies, for improved understanding of the
      infections and in designing disease control programs.

PMID- 27878429
TI  - Comparison of specular microscopy and ultrasound pachymetry before and after
      cataract surgery.
AB  - PURPOSE: To compare specular microscopy (Topcon SP-3000P, Topcon Corporation,
      Tokyo, Japan) and ultrasound (US) technology when evaluating central corneal
      thickness (CCT) prior to and after phacoemulsification. METHODS: Corneal edema
      was assessed in phacoemulsification patients due to senile cataract by measuring
      CCT preoperatively and 1 day, 1 month, and 3 months postoperatively. Bland-Altman
      analysis was performed to assess interchangeability between pachymetry techniques
      for each visit. Repeated measures analysis of variance was performed to evaluate
      variation in CCT agreement depending on the degree of corneal edema. RESULTS: One
      hundred and eighteen patients aged 73.9 +/- 10.1 years were recruited. Topcon SP
      3000P provided significant (p < 0.0001) lower CCT values than US with and without
      induced corneal edema. Mean differences between CCT techniques for baseline, 1
      day, 1 month and 3 months after cataract surgery were -28.9 +/- 22.6, -30.5 +/-
      41.4, -32.3 +/- 16.2 and -33.0 +/- 16.9 MUm, respectively. The systematic bias
      observed was not significantly different among the 4 visits (p = 0.59). The
      estimated limits of agreement (based on 1.96 standard deviation) were
      substantial, being 90.5, 165.8, 64.9 and 67.5 um at baseline, 1 day and 1 and 3
      months. CONCLUSIONS: Topcon SP-3000P provides similar systematic bias in
      comparison with US technique for CCT measurements regardless of the degree of
      corneal edema after phacoemulsification, which should be reduced after applying a
      constant calibration adjustment of ~30 MUm. However, interchangeability between
      techniques may be still limited by the notable random measurement error.

PMID- 27878430
TI  - Short-term safety of dexamethasone implant for treatment of macular edema due to
      retinal vein occlusion, in eyes with glaucoma or treated ocular hypertension.
AB  - PURPOSE: To report the short-term safety of dexamethasone implants to treat
      macular edema due to retinal vein occlusion (RVO), in eyes with treated glaucoma
      or ocular hypertension at baseline using an as-needed re-treatment regimen.
      METHODS: Retrospective clinical database study from two centers using the same
      electronic medical record system. Extracted data included: intraocular pressure
      (IOP), visual acuity (VA), central 1 mm retinal thickness (CRT) by optical
      coherence tomography, phakic status, number of injections, glaucoma treatment,
      and peri-operative complications. RESULTS: Thirty-three eyes of 33 patients on
      IOP-lowering treatment for glaucoma or ocular hypertension (OHT) at baseline and
      mean IOP of 16 mmHg at baseline received one to four (mean, 1.8; median, 1)
      dexamethasone implants over 18 months for RVO-related macular edema. Fourteen
      eyes (42 %) had IOP of >=21 mmHg, and three eyes (9 %) had IOP of >=35 mmHg at
      one or more visits during the study period. Nine of 14 eyes (64 %) with raised
      IOP required additional topical treatment only for a mean (SE) period of 8.5
      months (3.2), while the remaining five eyes (36 %) required long-term additional
      IOP-lowering treatment for a mean (SE) of 16 months (1.44). Surgery for IOP
      lowering was not required in any eye. Mean VA (SE) improved from 44 (3) ETDRS
      letters at baseline to 47 letters (5) at 2 months (p = 0.049), 48 (8) letters at
      6 months and 46 (4) letters at 12 months. Mean CRT (SE) improved from 530 (25)
      MUm at baseline to 323 (27) MUm at 2 months (p < 0.001), 498 (76) MUm at 6
      months, and 359 (25) MUm at 12 months (p < 0.001). CONCLUSION: The short-term IOP
      rise after intravitreal dexamethasone implant in eyes with glaucoma or ocular
      hypertension at baseline was acceptable and consistent with previous reports in
      patients without preexisting glaucoma. Treated OHT or glaucoma may not be a
      strict contraindication against the use of dexamethasone implant, but close
      monitoring of IOP is required.

PMID- 27878432
TI  - Histopathologic diagnosis of brain metastases: current trends in management and
      future considerations.
AB  - Confronted with brain metastases (BM), pathologists aim to rule out a primary
      central nervous system (CNS) tumor and to identify or verify the primary tumor
      site to guide the clinician to specific therapies. Apart from morphological
      features, ancillary immunohistochemical analysis is the most effective tool for
      characterizing a metastatic neoplasm of unknown origin. A limited array of
      antibodies is used, taking into account relevant clinical information and the
      known brain tropism of lung cancer, breast cancer and melanoma. Recently,
      targeted therapies have enriched the therapeutic arsenal, in particular for
      patients with non-small cell lung cancer or melanoma and for patients carrying
      molecular anomalies. These therapies can lead to a substantial tumor response,
      brain metastases included, which justifies rapid determination of a molecular
      profile. To combine different tools and provide timely results, good tumor sample
      management and careful attention at the pre-analytical phase are critical.
      Appropriate strategies for molecular and immunohistochemical analysis are needed
      to identify theranostic markers. This article aims to review the
      anatomopathological diagnostic approach for BM in the age of targeted therapies.

PMID- 27878431
TI  - Aqueous immune mediators in malignant uveal melanomas in comparison to benign
      pigmented intraocular tumors.
AB  - BACKGROUND: To examine the usefulness of measuring immune mediators in aqueous
      humor samples for differentiating malignant uveal melanoma from benign pigmented
      intraocular tumors. METHODS: Thirteen eyes of 13 patients with uveal melanoma
      were studied, and 13 eyes of 13 patients with benign pigmented intraocular tumors
      served as controls. Undiluted samples of aqueous humor were collected, and a
      cytometric bead array was used to determine the aqueous humor concentrations of
      35 immune mediators comprising 14 interleukins (IL), interferon-gamma, interferon
      gamma-inducible protein-10, monocyte chemoattractant protein (MCP)-1, macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation normal T
      cell expressed and secreted, monokine induced by interferon-gamma, basic
      fibroblast growth factor, Fas ligand, granzyme A, granzyme B, eotaxin, interferon
      inducible T-cell alpha chemoattractant, fractalkine, granulocyte macrophage
      colony-stimulating factor, granulocyte colony-stimulating factor, vascular
      endothelial growth factor, angiogenin, tumor necrosis factor-alpha, lymphotoxin
      alpha, and CD40L. RESULTS: Aqueous humor levels of angiogenin, IL-8, and MCP-1
      were significantly higher in eyes with malignant melanoma than in those with
      benign tumors (p < 0.05). CONCLUSIONS: Angiogenin, IL-8, and MCP-1 levels in
      aqueous humor may be potential markers for distinguishing malignant uveal
      melanoma from benign pigmented intraocular tumors, and may be a useful adjunct to
      histomorphology, diagnostic imaging, and other biomarkers for the diagnosis and
      appropriate clinical management of malignant uveal melanoma.

PMID- 27878433
TI  - High expression of long non-coding RNA ATB indicates a poor prognosis and
      regulates cell proliferation and metastasis in non-small cell lung cancer.
AB  - BACKGROUND AND AIM: Long non-coding RNAs (lncRNAs) have been demonstrated to act
      as a critical regulator in the processes of tumor biology. In this study, whether
      lncRNA-ATB is a potential indicator for non-small cell lung cancer (NSCLC) was
      investigated and its biological function in NSCLC was also determined. METHODS:
      The expression levels of lncRNA-ATB in NSCLC tissues and cell lines were
      measured. A549 cell line was explored to investigate the functions of lncRNA-ATB
      in NSCLC. RESULTS: Real-time PCR results showed that lncRNA-ATB expression was up
      regulated in both in NSCLC tissues and cell lines. High lncRNA-ATB expression in
      tumor tissue was associated with larger tumor size, lymph node metastasis, and
      distant metastasis in patients with NSCLC, respectively. In addition, the
      patients with high expression of lncRNA-ATB presented a lower survival
      probability. In vitro experiments showed that down-regulation of lncRNA-ATB
      promoted the cell apoptosis, whereas inhibited the cell viability, cell
      migration, and cell invasion. CONCLUSION: High expression of lncRNA-ATB indicated
      a poor prognosis and led to the cell proliferation and metastasis in NSCLC.

PMID- 27878434
TI  - Regional selection of the brain size regulating gene CASC5 provides new insight
      into human brain evolution.
AB  - Human evolution is marked by a continued enlargement of the brain. Previous
      studies on human brain evolution focused on identifying sequence divergences of
      brain size regulating genes between humans and nonhuman primates. However, the
      evolutionary pattern of the brain size regulating genes during recent human
      evolution is largely unknown. We conducted a comprehensive analysis of the brain
      size regulating gene CASC5 and found that in recent human evolution, CASC5 has
      accumulated many modern human specific amino acid changes, including two fixed
      changes and six polymorphic changes. Among human populations, 4 of the 6 amino
      acid polymorphic sites have high frequencies of derived alleles in East Asians,
      but are rare in Europeans and Africans. We proved that this between-population
      allelic divergence was caused by regional Darwinian positive selection in East
      Asians. Further analysis of brain image data of Han Chinese showed significant
      associations of the amino acid polymorphic sites with gray matter volume. Hence,
      CASC5 may contribute to the morphological and structural changes of the human
      brain during recent evolution. The observed between-population divergence of
      CASC5 variants was driven by natural selection that tends to favor a larger gray
      matter volume in East Asians.

PMID- 27878436
TI  - Peripheral nerve ultrasound scoring systems: benchmarking and comparative
      analysis.
AB  - Ultrasound of the nerves is an additive diagnostic tool to evaluate
      polyneuropathy. Recently, the need for standardized scoring systems has widely
      been discussed; different scores are described so far. Therefore, 327 patients
      with polyneuropathy were analyzed by ultrasound in our laboratory. Consequently,
      several ultrasound scoring tools were applied, i.e., the nerve pattern
      classification according to Padua et al. in all patients with CIDP and variants,
      the Bochum ultrasound score (BUS) and the neuritis ultrasound protocol in immune
      mediated neuritis, the ultrasound pattern sum score, the homogeneity score, and
      the nerve enlargement distribution score in all neuropathies if possible. For all
      scores good accuracy was found. Most patients with CIDP revealed hypoechoic
      enlarged nerves (Class 1), the BUS/NUP was useful to identify GBS (sensitivity
      >85%), MMN (100%) and CIDP (>70%), while the UPSS showed high sensitivity and
      positive/negative predictive values (N/PPV) in the diagnosis of GBS (>70%), CIDP
      (>85%) and axonal non-inflammatory neuropathies (>90%). Homogeneous nerves were
      found in most CMT1 patients (66.7%), while immune-mediated neuropathies mostly
      show regional nerve enlargement. The HS was suitable to identify CMT patients
      with an HS >=5 points. All scores were easily applicable with high accuracy. The
      former-reported results could be similarly confirmed. However, all sores have
      some incompleteness concerning unselected polyneuropathy population, particularly
      rare and focal types. Scoring systems are useful and easily applicable. They show
      high accuracy in certain neuropathies, but also offer some gaps and can,
      therefore, only be used in addition to standard diagnostic routines such as
      electrophysiology.

PMID- 27878435
TI  - Novel phenotypes and loci identified through clinical genomics approaches to
      pediatric cataract.
AB  - Pediatric cataract is highly heterogeneous clinically and etiologically. While
      mostly isolated, cataract can be part of many multisystem disorders, further
      complicating the diagnostic process. In this study, we applied genomic tools in
      the form of a multi-gene panel as well as whole-exome sequencing on unselected
      cohort of pediatric cataract (166 patients from 74 families). Mutations in
      previously reported cataract genes were identified in 58% for a total of 43
      mutations, including 15 that are novel. GEMIN4 was independently mutated in
      families with a syndrome of cataract, global developmental delay with or without
      renal involvement. We also highlight a recognizable syndrome that resembles
      galactosemia (a fulminant infantile liver disease with cataract) caused by
      biallelic mutations in CYP51A1. A founder mutation in RIC1 (KIAA1432) was
      identified in patients with cataract, brain atrophy, microcephaly with or without
      cleft lip and palate. For non-syndromic pediatric cataract, we map a novel locus
      in a multiplex consanguineous family on 4p15.32 where exome sequencing revealed a
      homozygous truncating mutation in TAPT1. We report two further candidates that
      are biallelically inactivated each in a single cataract family: TAF1A (cataract
      with global developmental delay) and WDR87 (non-syndromic cataract). In addition
      to positional mapping data, we use iSyTE developmental lens expression and gene
      network analysis to corroborate the proposed link between the novel candidate
      genes and cataract. Our study expands the phenotypic, allelic and locus
      heterogeneity of pediatric cataract. The high diagnostic yield of clinical
      genomics supports the adoption of this approach in this patient group.

PMID- 27878437
TI  - Neurosarcoidosis: a clinical approach to diagnosis and management.
AB  - Sarcoidosis is a rare but important cause of neurological morbidity, and
      neurological symptoms often herald the diagnosis. Our understanding of
      neurosarcoidosis has evolved from early descriptions of a uveoparotid fever to
      include presentations involving every part of the neural axis. The diagnosis
      should be suspected in patients with sarcoidosis who develop new neurological
      symptoms, those presenting with syndromes highly suggestive of neurosarcoidosis,
      or neuro-inflammatory disease where more common causes have been excluded.
      Investigation should look for evidence of neuro-inflammation, best achieved by
      contrast-enhanced brain magnetic resonance imaging and cerebrospinal fluid
      analysis. Evidence of sarcoidosis outside the nervous system should be sought in
      search of tissue for biopsy. Skin lesions should be identified and biopsies
      taken. Chest radiography including high-resolution computed tomography is often
      informative. In difficult cases, fluorodeoxyglucose positron emission tomography
      and gallium-67 imaging may identify subclinical disease and a target for biopsy.
      Symptomatic patients should be treated with corticosteroids, and if clinically
      indicated other immunosuppressants such as hydroxychloroquine, azathioprine,
      cyclophosphamide or methotrexate should be added. Anti-tumour necrosis factor
      alpha therapies may be considered in refractory disease but caution should be
      exercised as there is evidence to suggest they may unmask disease.

PMID- 27878438
TI  - Interdependence of clinical factors predicting cognition in children with
      tuberous sclerosis complex.
AB  - Cognitive development in patients with tuberous sclerosis complex is highly
      variable. Predictors in the infant years would be valuable to counsel parents and
      to support development. The aim of this study was to confirm factors that have
      been reported to be independently correlated with cognitive development. 102
      patients included in this study were treated at the ENCORE-TSC expertise center
      of the Erasmus Medical Center-Sophia Children's Hospital. Data from the first 24
      months of life were used, including details on epilepsy, motor development and
      mutation status. Outcome was defined as cognitive development (intellectual
      equivalent, IE) as measured using tests appropriate to the patients age and
      cognitive abilities (median age at testing 8.2 years, IQR 4.7-12.0). Univariable
      and multivariable regression analyses were used. In a univariable analysis,
      predictors of lower IE were: the presence of infantile spasms (beta = -18.3, p =
      0.000), a larger number of antiepileptic drugs used (beta = -6.3, p = 0.000),
      vigabatrin not used as first drug (beta = -14.6, p = 0.020), corticosteroid
      treatment (beta = -33.2, p = 0.005), and a later age at which the child could
      walk independently (beta = -2.1, p = 0.000). An older age at seizure onset
      predicted higher IE (beta = 1.7, p = 0.000). In a multivariable analysis, only
      age at seizure onset was significantly correlated to IE (beta = 1.2, p = 0.005),
      contributing to 28% of the variation in IE. In our cohort, age at seizure onset
      was the only variable that independently predicted IE. Factors predicting
      cognitive development could aid parents and physicians in finding the appropriate
      support and schooling for these patients.

PMID- 27878439
TI  - Multiple sclerosis and inflammatory bowel diseases: a systematic review and meta
      analysis.
AB  - The association between multiple sclerosis (MS) and inflammatory bowel disease
      (IBD) has been suggested, apart from their common epidemiological and
      immunological patterns, also due to observations of increased incidence of both
      IBD among MS patients and MS among IBD patients. We estimated the risk of
      concurrent IBD and MS comorbidity, using data from all available case-control
      studies. We calculated the corresponding Risk ratios (RRs) in each included case
      control study to express the risk of IBD and MS concurrence at a given
      population. We performed additional subgroup analyses according to the type of
      registry from which the data of the cases were exported (IBD or MS registry) and
      the IBD type (Crohn's disease, CD or Ulcerative colitis, UC). We included 10
      studies, comprising a total of 1,086,430 patients (0.08% of them with concurrent
      IBD and MS). Pooled RR for IBD/MS comorbitity was 1.54 (95% CI 1.40-1.67; p <
      0.0001) with no differences (p = 0.91) among IBD and MS registries (RR 1.53, 95%
      CI 1.36-1.72, p < 0.001 for MS comorbidity in IBD patients vs. RR 1.55, 95% CI
      1.32-1.81, p < 0.001 for IBD comorbidity in MS patients). No difference was also
      found on the risk of MS comorbidity among patients with CD or UC (RR 1.52, 95% CI
      1.34-1.72, p < 0.001 vs. RR 1.55, 95% CI 1.38-1.74, p < 0.001; p for subgroup
      differences: 0.84). In all analyses no evidence of heterogeneity or publication
      bias was detected. Both IBD and MS patients seem to have a fifty-percent
      increased risk of MS or IBD comorbidity, respectively, with no apparent
      differences between patients with CD or UC.

PMID- 27878440
TI  - Cognitive dysfunction in patients with spinocerebellar ataxia type 6.
AB  - The aim of this study was to assess the cognitive functions of patients with
      spinocerebellar ataxia type 6 (SCA6). We examined 13 patients with genetically
      confirmed SCA6 and 13 healthy control subjects matched for age, years of
      education, global cognitive status, and intellectual ability. We administered
      verbal memory (word recall and word recognition), executive function (digit span,
      category and letter fluency, Frontal Assessment Battery, and Trail Making Test-A
      and B), and visuospatial construction (figure copying) tests. We found that the
      patients with SCA6 had significantly lower scores on the demanding word recall
      and letter fluency tests compared to the control subjects, while word recognition
      was well preserved in the patients with SCA6. The other executive functions
      tested, as well as visuospatial construction, were preserved in the SCA6 group.
      However, although memory encoding and storage processes were preserved, the
      retrieval of memorized information concerning frontal function might be
      selectively affected in patients with SCA6 compared to in control subjects. The
      impaired word recall and letter fluency noted in patients with SCA6 were
      interpreted as being related to a word-retrieval disability. Such dysfunctions
      may be attributed to damage in the frontal-cerebellum circuit owing to SCA6.

PMID- 27878441
TI  - Long-term treatment of transthyretin familial amyloid polyneuropathy with
      tafamidis: a clinical and neurophysiological study.
AB  - Tafamidis is a transthyretin (TTR) stabilizer recently approved to slow the
      neurologic impairment in TTR familial amyloid polyneuropathy (TTR-FAP). The
      pivotal studies on Tafamidis reported encouraging results on the short term, in
      the early onset Val30Met-TTR-FAP patients at an early stage of the neuropathy.
      However, the effect of the drug in the non-Val30Met patients, at a more advanced
      stage of the disease and on the long term, is less known. In this study, we
      report the effect of Tafamidis in 43 TTR-FAP patients with a variety of
      pathogenic mutations, including 53% of non-Val30Met variants, at different stages
      of neuropathy followed on the long term. General and neurological assessment was
      performed in a standardized protocol every 6-12 months along with
      neurophysiological variables, including testing of small nerve fibres. The mean
      follow-up under treatment was 2 years with a subset of 26 patients treated for 3
      years. Overall, Tafamidis was well tolerated. A significant clinical
      deterioration of the neuropathy and the patient's general condition was observed
      across the 3 years follow-up, although neurophysiological parameters remained
      stable for the first 2 years. In contrast, patients had a significant increase of
      BMI under treatment. Deterioration of the neuropathy correlated to an older age
      at disease onset or treatment initiation and to poor clinical status at baseline.
      A higher BMI at baseline was associated with a lower progression of the
      neuropathy. About one-third of the patients who received 3 years of tafamidis had
      still preserved walking capacity or good clinical condition, suggesting that
      tafamidis slowed the disease progression in some patients. Overall, our work
      shows that tafamidis is well tolerated in TTR-FAP but does not prevent the steady
      progression of the neuropathy on the long term. Age, neurologic status, and
      general condition at baseline appear to be best predictors of tafamidis efficacy
      on the neurological function.

PMID- 27878442
TI  - Clinical and neurophysiological risk factors for falls in patients with bilateral
      vestibulopathy.
AB  - Patients with bilateral vestibular failure (BVF) exhibit imbalance when standing
      and walking that is linked to a higher fall risk. The purpose of this study was
      to identify risk factors for falls in BVF. We therefore systematically
      investigated the interrelationship of clinical and demographic characteristics,
      gait impairments, and the fall frequency of these patients. Clinical and
      demographic characteristics as well as quantitative measures of gait performance
      on a pressure-sensitive gait carpet were collected from 55 patients with
      different etiologies of BVF. Clinical and demographic data as well as
      spatiotemporal gait characteristics were used for ANOVA testing and a logistic
      regression model with categorized fall events as dependent variables. The
      impairment of peripheral vestibular function, duration of disease, and the
      overall gait status were not associated with the history of falls in patients
      with BVF. In contrast, the most predictive factors for falls in BVF were an
      increase in temporal gait variability, especially at slow walking speeds (p <
      0.001; OR = 1.3), and the presence of a concomitant peripheral neuropathy (p <
      0.045; OR = 3.6). BVF patients with a high risk of falling exhibit specific gait
      alterations in a speed-dependent manner. In particular, increased gait
      fluctuations during slow walking are most predictive for an increased fall risk.
      The presence of a concomitant peripheral neuropathy further critically impairs
      postural stability in these patients. Clinical assessment of both these aspects
      is therefore important to identify those patients at a particularly high fall
      risk and to initiate preventive procedures early.

PMID- 27878444
TI  - Is a mobile emergency severity index (ESI) triage better than the paper ESI?
AB  - This study aims to evaluate the mobile emergency severity index (ESI) tool in
      terms of validity compared with the original ESI triage. The original ESI and
      mobile ESI were used with patients at the Department of Emergency Medicine,
      Ramathibodi Hospital, Thailand. Eligible patients were evaluated by sixth-year
      medical students/emergency physicians using either the original or mobile ESI.
      The ESI results for each patient were compared with the standard ESI. Concordance
      and kappa statistics were calculated for pairs of the evaluators. There were 486
      patients enrolled in the study; 235 patients (48.4%) were assessed using the
      mobile ESI, and 251 patients (51.6%) were in the original ESI group. The baseline
      characteristics of patients in both groups were mostly comparable except for the
      ED visit time. The percentages of concordance and kappa statistics in the
      original ESI group were lower than in the mobile group in all three comparisons
      (medical students vs gold standard, emergency physicians vs gold standard, and
      medical students vs emergency physicians). The highest kappa in the original ESI
      group is 0.69, comparing emergency physicians vs gold standard, while the lowest
      kappa in the application group is 0.84 comparing the medical students vs gold
      standard. Both medical students and emergency physicians are more confident with
      the mobile ESI application triage. In conclusion, the mobile ESI has better inter
      rater reliability, and is more user-friendly than the original paper form.

PMID- 27878443
TI  - Real-world effectiveness of natalizumab and fingolimod compared with self
      injectable drugs in non-responders and in treatment-naive patients with multiple
      sclerosis.
AB  - In this independent, multicentre post-marketing study we directly compared the
      effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs
      (INJ), in non-responders to first immunomodulating treatment and in highly active
      treatment-naive patients with multiple sclerosis. As main outcome measure we
      considered the proportions of patients with no evidence of disease activity (NEDA
      3), defined as absence of relapses, disability worsening and radiological
      activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer
      acetate (GA) [dataset A] and 216 highly active treatment-naives [dataset B] were
      followed up to 24 months from the beginning of NTZ, FNG or INJ, i.e. switching
      from IFNB to GA or viceversa (in the case of non-responders) or starting high
      dose IFNB (in the case of highly active treatment-naives). Propensity score
      matching in a 1:1:1 ratio was used to select only patients with similar baseline
      characteristics, retaining 330 and 120 patients in dataset A and B, respectively.
      In dataset A, the 24-month proportion with NEDA-3 was greater in both NTZ group
      (67%) and FNG group (42%) than in INJ group (35%) (p <= 0.016); however, NTZ was
      superior to FNG in promoting the attainment of NEDA-3 status (p = 0.034). In
      dataset B, the 24-month proportion with NEDA-3 was greater in NTZ group (75%) and
      FNG group (67%) than in INJ group (40%), but the small cohort sizes most likely
      prevented the detection of any statistically significant difference. Our study
      provides real-world evidence that NTZ was more effective than both FNG and INJ in
      non-responders, while it could seem that, in highly active treatment-naives, NTZ
      was as effective as FNG and both were superior to INJ.

PMID- 27878446
TI  - Accuracy assessment methods of tissue marker clip placement after 11-gauge vacuum
      assisted stereotactic breast biopsy: comparison of measurements using direct and
      conventional methods.
AB  - BACKGROUND: The objective of the study was to compare direct measurement with a
      conventional method for evaluation of clip placement in stereotactic vacuum
      assisted breast biopsy (ST-VAB) and to evaluate the accuracy of clip placement
      using the direct method. METHODS: Accuracy of clip placement was assessed by
      measuring the distance from a residual calcification of a targeted calcification
      clustered to a clip on a mammogram after ST-VAB. Distances in the craniocaudal
      (CC) and mediolateral oblique (MLO) views were measured in 28 subjects with
      mammograms recorded twice or more after ST-VAB. The difference in the distance
      between the first and second measurements was defined as the reproducibility and
      was compared with that from a conventional method using a mask system with
      overlap of transparent film on the mammogram. The 3D clip-to-calcification
      distance was measured using the direct method in 71 subjects. RESULTS: The
      reproducibility of the direct method was higher than that of the conventional
      method in CC and MLO views (P = 0.002, P < 0.001). The median 3D clip-to
      calcification distance was 2.8 mm, with an interquartile range of 2.0-4.8 mm and
      a range of 1.1-36.3 mm. CONCLUSION: The direct method used in this study was more
      accurate than the conventional method, and gave a median 3D distance of 2.8 mm
      between the calcification and clip.

PMID- 27878447
TI  - Morbidity and healthcare costs of vascular anomalies: a national study.
AB  - PURPOSE: This study aimed to define morbidities and costs related to modern-day
      medical care for children with vascular anomalies. METHODS: We reviewed the 2003
      2009 Kids' Inpatient Database for pediatric patients (age < 21 years)
      hospitalized with hemangioma, arteriovenous malformation (AVM), or lymphatic
      malformation (LM). Patient characteristics, hospital complications, and hospital
      charges were compared by vascular anomaly type. Multivariable linear regression
      modeling was used to determine predictors of increasing hospital costs for
      patients with AVMs. RESULTS: In total, 7485 pediatric inpatients with vascular
      anomalies were identified. Frequently associated complications included chronic
      anemia (4.0%), sepsis (4.6%), and hypertension (2.4%). Children with AVM had the
      highest rate of in-hospital mortality, compared to those with hemangiomas or LM
      (1.0% vs. 0.1% vs. 0.3%, p < 0.001). AVMs were also associated with the highest
      median hospital charge, more than twice the cost for hemangiomas or LM ($45,875
      vs. $18,909 vs. $18,919; p < 0.001). CONCLUSIONS: There is a significant rate of
      morbidity in children with vascular anomalies, most often from blood loss and
      infection. The greater cost of AVM care may be related to the higher mortality
      rate, associated complications, and complexity of procedures required treating
      them. Cost-effective management of vascular anomalies should target prevention
      and the early recognition of both chronic comorbidities and acute complications.

PMID- 27878445
TI  - Can non-invasive ventilation modify central venous pressure? Comparison between
      invasive measurement and ultrasonographic evaluation.
AB  - Central venous pressure (CVP) is primarily measured to assess intravascular
      volume status and heart preload. In clinical practice, the measuring device most
      commonly used in emergency departments and intensive care units, is an electronic
      transducer that interconnects a central venous catheter (CVC) with a monitoring
      system. Non-invasive ventilation (NIV) consists in a breathing support that
      supplies a positive pressure in airways through a mask or a cask though not using
      an endotracheal prosthesis. In emergency settings, non-invasive ultrasonography
      evaluation of CVP, and hence of intravascular volume status entail the
      measurement by a subxiphoid approach of inferior vena cava diameter and its
      variations in relation to respiratory activity. In the literature, there are many
      studies analyzing the ability to estimate CVP through ultrasonography, rating
      inspiratory and expiratory vena cava diameters and their ratio, defined as
      inferior vena cava collapsibility index (IVC-CI). At the same time, the effects
      of invasive mechanical ventilation on blood volume and the correlation during
      ventilation between hemodynamic invasive measurement of CVP and inferior vena
      cava diameters have already been demonstrated. Nevertheless, there are no
      available data regarding the hemodynamic effects of NIV and the potential
      correlations during this kind of ventilation between invasive and non-invasive
      CVP measurements. Therefore, this study aims to understand whether there exists
      or not an interrelationship between the values of CVP assessed invasively through
      a CVC and non-invasively through the IVC-CI in patients with severe respiratory
      distress, and above all to evaluate if these means of assessment can be
      influenced using NIV.

PMID- 27878448
TI  - A review of ecosystem service benefits from wild bees across social contexts.
AB  - In order to understand the role of wild bees in both social and ecological
      systems, we conducted a quantitative and qualitative review of publications
      dealing with wild bees and the benefits they provide in social contexts. We
      classified publications according to several attributes such as services and
      benefits derived from wild bees, types of bee-human interactions, recipients of
      direct benefits, social contexts where wild bees are found, and sources of
      changes to the bee-human system. We found that most of the services and benefits
      from wild bees are related to food, medicine, and pollination. We also found that
      wild bees directly provide benefits to communities to a greater extent than
      individuals. In the social contexts where they are found, wild bees occupy a
      central role. Several drivers of change affect bee-human systems, ranging from
      environmental to political drivers. These are the areas where we recommend making
      interventions for conserving the bee-human system.

PMID- 27878449
TI  - Pseudomyogenic Hemangioendothelioma: A Vascular Tumor Previously Undescribed in
      the Oral Cavity.
AB  - The pseudomyogenic hemangioendothelioma (PMH) is a low-grade malignant vascular
      neoplasm of different tissue planes including skin and soft tissue. Primary
      tumors in the skeletal muscle and bone have also been diagnosed. The PMH was
      introduced into the WHO classification of tumors of soft tissue and bone in 2013.
      This is the first description of oral involvement. A 21-year-old female presented
      with a 2-month old swelling of her gingiva. The swelling appeared red in color
      and was soft in consistency. A clinical diagnosis of a pyogenic granuloma was
      made and an incisional biopsy was submitted for histopathological evaluation. The
      lesion consisted of a proliferation of spindle and epithelioid looking cells.
      Cells were arranged in loose fascicles and sheets. Rhabdomyoblast-like cells were
      also seen. No mitotic figures were present. Lesional cells were reactive to
      cytokeratin AE1/AE3 and CD31. Lesional cell reactivity to S100 protein, HMB 45,
      SMA, Desmin and CD34 was negative. Following the diagnosis, a wide excision for
      clear margins was performed. No recurrence has been reported 2 years since the
      removal. The PMH is a cutaneous tumor that behaves in an indolent fashion. This
      is the first report of oral involvement by this neoplasm. Recognition of its
      histopathological features and immunohistochemical reactivity will prevent
      misadventures in the diagnosis of oral lesions.

PMID- 27878450
TI  - Mass spectrometry based proteomics profiling of human monocytes.
AB  - Human monocyte is an important cell type which is involved in various complex
      human diseases. To better understand the biology of human monocytes and
      facilitate further studies, we developed the first comprehensive proteome
      knowledge base specifically for human monocytes by integrating both in vivo and
      in vitro datasets. The top 2000 expressed genes from in vitro datasets and 779
      genes from in vivo experiments were integrated into this study. Altogether, a
      total of 2237 unique monocyte-expressed genes were cataloged. Biological
      functions of these monocyte-expressed genes were annotated and classified via
      Gene Ontology (GO) analysis. Furthermore, by extracting the overlapped genes from
      in vivo and in vitro datasets, a core gene list including 541 unique genes was
      generated. Based on the core gene list, further gene-disease associations,
      pathway and network analyses were performed. Data analyses based on multiple
      bioinformatics tools produced a large body of biologically meaningful
      information, and revealed a number of genes such as SAMHD1, G6PD, GPD2 and ENO1,
      which have been reported to be related to immune response, blood biology, bone
      remodeling, and cancer respectively. As a unique resource, this study can serve
      as a reference map for future in-depth research on monocytes biology and monocyte
      involved human diseases.

PMID- 27878452
TI  - Inheritance and effectiveness of two transgenes determining PVY resistance in
      progeny from crossing independently transformed tobacco lines.
AB  - Genetic transformation of plants allows us to obtain improved genotypes enriched
      with the desired traits. However, if transgenic lines were to be used in breeding
      programs the stability of inserted transgenes is essential. In the present study,
      we followed the inheritance of transgenes in hybrids originated from crossing two
      transgenic tobacco lines resistant to Potato virus Y (PVY): MN 944 LMV with the
      transgene containing Lettuce mosaic virus coat protein gene (LMV CP) and AC Gayed
      ROKY2 with PVY replicase gene (ROKY2). Progeny populations generated by
      successive self-pollination were analyzed with respect to the transgene
      segregation ratio and resistance to Potato virus Y in tests carried out under
      greenhouse conditions. The presence of the virus in inoculated plants was
      detected by DAS-ELISA method. The results demonstrated the Mendelian fashion of
      inheritance of transgenes which were segregated independently and stably. As a
      result, we obtained T4 generation of hybrid with both transgenes stacked and
      which was highly resistant to PVY.

PMID- 27878453
TI  - Evaluation of stability and validation of reference genes for RT-qPCR expression
      studies in rice plants under water deficit.
AB  - Many studies use strategies that allow for the identification of a large number
      of genes expressed in response to different stress conditions to which the plant
      is subjected throughout its cycle. In order to obtain accurate and reliable
      results in gene expression studies, it is necessary to use reference genes, which
      must have uniform expression in the majority of cells in the organism studied.
      RNA isolation of leaves and expression analysis in real-time quantitative
      polymerase chain reaction (RT-qPCR) were carried out. In this study, nine
      candidate reference genes were tested, actin 11 (ACT11), ubiquitin conjugated to
      E2 enzyme (UBC-E2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta
      tubulin (beta-tubulin), eukaryotic initiation factor 4alpha (eIF-4alpha),
      ubiquitin 10 (UBQ10), ubiquitin 5 (UBQ5), aquaporin TIP41 (TIP41-Like) and
      cyclophilin, in two genotypes of rice, AN Cambara and BRS Querencia, with
      different levels of soil moisture (20%, 10% and recovery) in the vegetative (V5)
      and reproductive stages (period preceding flowering). Currently, there are
      different softwares that perform stability analyses and define the most suitable
      reference genes for a particular study. In this study, we used five different
      methods: geNorm, BestKeeper, DeltaCt method, NormFinder and RefFinder. The
      results indicate that UBC-E2 and UBQ5 can be used as reference genes in all
      samples and softwares evaluated. The genes beta-tubulin and eIF-4alpha,
      traditionally used as reference genes, along with GAPDH, presented lower
      stability values. The gene expression of basic leucine zipper (bZIP23 and bZIP72)
      was used to validate the selected reference genes, demonstrating that the use of
      an inappropriate reference can induce erroneous results.

PMID- 27878455
TI  - Structural Insight into Binding Mode of 9-Hydroxy Aristolochic Acid, Diclofenac
      and Indomethacin to PLA2.
AB  - Phospholipase A2 (PLA2) catalyzes the hydrolysis of phospholipids into
      arachidonic acid and lysophospholipids. Arachidonic acid is modified by
      cyclooxygenases into active compounds called eicosanoids that act as signaling
      molecules in a number of physiological processes. Excessive production of
      eicosanoids leads to several pathological conditions such as inflammation. In
      order to block the inflammatory effect of these compounds, upstream enzymes such
      as PLA2 are valid targets. In the present contribution, molecular dynamic
      analysis was performed to evaluate the binding of diclofenac, 9-hydroxy
      aristolochic acid (9-HAA) and indomethacin to PLA2. Obtained results revealed
      that 9-HAA could form a more stable complex with PLA2 when compared to diclofenac
      and indomethacin. Furthermore, analysis of intermolecular binding energy
      components indicated that hydrophobic interactions were dominant in binding
      process. On the basis of obtained data, inhibitors bearing fused rings with
      hydrogen acceptor/donor substituent(s) interacted with His48 and Asp49 residues
      of the active site. More affinity toward PLA2 might be envisaged through
      negatively charged moieties via interaction with Trp31, Lys34 and Lys69.

PMID- 27878454
TI  - Pectinase production by Aspergillus giganteus in solid-state fermentation:
      optimization, scale-up, biochemical characterization and its application in olive
      oil extraction.
AB  - The application of pectinases in industrial olive-oil processes is restricted by
      its production cost. Consequently, new fungal strains able to produce higher
      pectinase titers are required. The aim of this work was to study the capability
      of Aspergillus giganteus NRRL10 to produce pectinolytic enzymes by SSF and
      evaluate the application of these in olive-oil extraction. A. giganteus was
      selected among 12 strains on the basis of high pectinolytic activity and
      stability. A mixture composed by wheat bran, orange, and lemon peels was selected
      as the best substrate for enzyme production. Statistical analyses of the
      experimental design indicated that pH, temperature, and CaCl2 are the main
      factors that affect the production. Subsequently, different aeration flows were
      tested in a tray reactor; the highest activity was achieved at 20 L min-1 per
      kilogram of dry substrate (kgds). Finally, the pectinolytic enzymes from A.
      giganteus improved the oil yield and rheological characteristics without
      affecting oil chemical properties.

PMID- 27878456
TI  - An Improved Protein Surface Extraction Method Using Rotating Cylinder Probe.
AB  - For extraction of information on binding sites of a protein, the commonly known
      geometry-based methods utilize the corresponding PDB file to extract its surface
      as a first step. Finally, the surface is used to find the binding site atoms. As
      shown in this paper work, since none of the mostly used surface extraction
      methods can retrieve a sizeable percentage of the binding site atoms, the scope
      of development of a better method remains. In this direction, this paper presents
      a new benchmarking criteria based on utilization of binding site information to
      compare performance of these surface extraction methods. Also, a new surface
      extraction method is introduced based on the use of a rotating cylinder probe
      adapting from the work of Weisel et al. (Chem Cent J 1:7-23, 2007. doi:
      10.1186/1752-153X-1-7 ). The result of the new method shows a significant
      improvement of performance in comparison to the existing methods.

PMID- 27878451
TI  - Beyond Genetics: What Causes Type 1 Diabetes.
AB  - Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated
      beta cell destruction in the pancreas of genetically susceptible individuals.
      Extensive familial and population genetic studies uncovered the strong linkage
      and association between HLA gene variants and T1D. Non-HLA genes have also been
      associated with T1D, such as INS, CTLA4, and PTPN22. T1D is considered as one of
      the most heritable common diseases. However, evidence that monozygotic twins have
      incomplete concordance of disease susceptibility provides convincing proof that
      environmental factors also play important roles in the pathogenesis of the
      disease. Environmental factors can induce the alterations of gene expression via
      epigenetic mechanisms. Epigenetic modifications refer to the alterations in gene
      expression without changes of the DNA sequence, but instead occur as a result of
      DNA methylation, histone modifications, and miRNA regulation. Aberrant epigenetic
      modifications will cause the dysregulation of gene expression, thus leading to a
      variety of human diseases. There are significant differences in DNA methylation,
      histone modifications, and miRNA profiling found in T1D patients compared with
      healthy individuals. Epigenetic modifications contribute to the pathogenesis of
      T1D mainly by regulating the expression of susceptible genes in T1D. These
      susceptible genes are involved in antigen presentation (such as HLA), immune
      tolerance (such as FOXP3 and CTLA4), autoreactive T cell response (such as
      GAD65), and beta cell functions (such as INS). A better understanding of
      epigenetic mechanisms for regulating susceptible genes of T1D will help identify
      candidates that target epigenetic pathways to control and/or prevent T1D.
      Knowledge of epigenetic changes in T1D also provides us with potential biomarkers
      for diagnosis, prognostication, personalized treatment, and prevention of the
      disease.

PMID- 27878457
TI  - Poorly understood and often miscategorized congenital umbilical cord hernia: an
      alternative repair method.
AB  - PURPOSE: Umbilical cord hernia is poorly understood and often miscategorized as
      "omphalocele minor". Careless clamping of the cord leads to iatrogenic gut injury
      in the situation of umbilical cord hernia. This study aimed to determine the
      characteristics and outcomes of umbilical cord hernias. We also highlight an
      alternative repair method for umbilical cord hernias. METHODS: We recorded 15
      cases of umbilical cord hernias over 10 years. The patients' data were
      retrospectively reviewed, and preoperative preparation of the newborn,
      gestational age, birth weight, other associated malformations, surgical technique
      used, enteral nutrition, and length of hospitalization were recorded. RESULTS:
      This study included 15 neonates with umbilical cord hernias. The mean gestational
      age at the time of referral was 38.2 +/- 2.1 <weeks. Mean birth weight was 3094.3
      +/- 636.8 g. Four infants had associated malformations, including agenesis of the
      right kidney, left kidney with a duplex system, coarctation of the aorta,
      ventricular septal defect, meningocele, club foot, and choanal atresia. Surgical
      exploration was carried out in all of the neonates and they underwent corrective
      surgery with good outcomes. CONCLUSIONS: In an umbilical cord hernia, the body
      folds develop normally and form the umbilical ring. The double purse-string
      technique is easy to apply and produces satisfactory cosmetic results in neonates
      with umbilical cord hernias.

PMID- 27878458
TI  - Totally extraperitoneal (TEP) bilateral hernioplasty using the Single Site(r)
      robotic da Vinci platform (DV-SS TEP): description of the technique and
      preliminary results.
AB  - PURPOSE: Laparoendoscopic single site totally extraperitoneal (TEP) hernia repair
      showed to be a feasible alternative to conventional laparoscopic hernia repair;
      nevertheless single site surgery, with the loss of instruments triangulation can
      be a demanding procedure. To overcome those hurdles, the Single Site(r) (SS)
      platform of the da Vinci (DV) Si robotic system enables to perform surgical
      procedures through a 25-mm skin incision, with a stable 3D vision and restoring
      an adequate triangulation of the surgical instruments. We present in details the
      technique and the preliminary results of DV-SS TEP, to our knowledge the first
      cases reported in literature. METHODS: In March 2016, three consecutive male
      patients (mean age 46.6 years-mean BMI 25.3) with bilateral symptomatic inguinal
      hernia were submitted to DV-SS TEP in our institutions. Feasibility, codification
      of the technique, operative time and perioperative outcomes were recorded.
      RESULTS: All the procedures were completed as scheduled, with no conversion to
      other techniques. Mean operative time was 98.6 min, ranging between 155 and 55
      min, reflecting the learning curve of the operating room team on this new
      procedure. No intraoperative or postoperative complications were experienced and
      all the patients were discharged within 24 h after surgery. Patients reported
      satisfactory postoperative course, with no recurrence of inguinal hernia and
      satisfaction in cosmetic result at 6-month follow-up. CONCLUSIONS: DV-SS TEP
      inguinal hernia repair showed to be feasible and effective surgical option for
      bilateral groin hernia repair. Patients' outcome was uneventful, with optimal
      cosmetic results. Further studies comparing this innovative technique to TEP or
      LESS TEP should be promoted.

PMID- 27878460
TI  - Comparative analysis of common regions found in babuviruses and alphasatellite
      molecules.
AB  - Viruses in the genus Babuvirus have multi-component ssDNA genomes and often
      associate with alphasatellite molecules containing two common motifs, a common
      region stem-loop (CR-SL) involved in initiation of rolling-circle replication and
      a common-region major (CR-M) motif involved in secondary-strand synthesis. We
      compared known babuvirus genome components and alphasatellite CR-SL and CR-M
      sequences, defining five divergent CR-SL sequence classes. We identified iterated
      sequence elements in babuvirus genome components that have particularly conserved
      sequences and spatial arrangements between known babuviruses.

PMID- 27878459
TI  - Stapled Mesh stomA Reinforcement Technique (SMART) in the prevention of
      parastomal hernia: a single-centre experience.
AB  - PURPOSE: Parastomal hernia remains a frequent complication following creation of
      an abdominal stoma. Previous interests have centred around the exploration of
      methods to repair; however, prophylactic mesh placement has demonstrated its
      efficacy in reduction of parastomal hernia. The aim of this retrospective
      analysis was to evaluate the outcomes of Stapled Mesh stomA Reinforcement
      Technique (SMART) in terms of parastomal hernia occurrence rate and mesh-related
      complications. METHODS AND MATERIALS: All patients operated with an abdominal
      perineal resection or Hartmann's procedure with SMART from November 2013 to March
      2016 were included. Patient demographics, operative details and stoma-related
      symptoms were collected. Patients were examined clinically by the medical team
      and also reviewed independently by a specialist stoma care nurse for signs of
      stoma-related complications. As part of oncological follow-up, CT scans were
      available for review for evidence of parastomal herniation. RESULTS: 14 patients
      (mean age 76 years) were included in the analysis. All the SMART cases were
      successfully completed with no intraoperative or immediate post-operative
      complications. No cases of mesh-related complications such as infection,
      immediate stomal prolapse, stenosis, retraction, stomal obstruction, mesh erosion
      or fistulation were observed. No mesh removal was required. There were two cases
      of parastomal hernia detected on CT scan. Both cases have remained asymptomatic
      no intervention was required at this stage. Median follow-up was 24 months.
      CONCLUSION: Our medium-term experience has demonstrated the efficacy of SMART in
      the reduction of parastomal hernia occurrence. With appropriate learning curve,
      parastomal hernia can be prevented.

PMID- 27878462
TI  - Enterovirus A71 and coxsackievirus A16 show different replication kinetics in
      human neuronal and non-neuronal cell lines.
AB  - Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are closely related
      enteroviruses that cause hand, foot and mouth disease (HFMD) in children. Serious
      neurological complications almost always occur in EV-A71 infection, but are rare
      in CV-A16 infection. Based on the hypothesis that this may be because EV-A71
      infects neuronal cells more easily than CV-A16, we compared virus infection,
      replication and spread of EV-A71 and CV-A16 in SK-N-SH cells. We found that CV
      A16 invariably showed significantly lower replication and caused less necrotic
      cell death in SK-N-SH cells, compared with EV-A71. This was not due to a lower
      proportion of CV-A16-infected cells, since both viruses showed similar
      proportions of infected cells at all time points analyzed. Furthermore, reduced
      replication of CV-A16 in SK-N-SH cells does not appear to be due to limited viral
      receptor availability, which might limit viral entry, because experiments with
      viral RNA-transfected cells showed the same results as for live virus infections.
      On the other hand, no differences were observed between EV-A71 and CV-A16 in RD
      cells and results were generally similar in RD cells for both viruses. Taken
      together, our findings suggest that the poor growth of CV-A16 and EV-A71in SK-N
      SH cells, compared with RD cells, may be due to cell type-specific restrictions
      on viral replication and spread. Furthermore, the lower viral replication and
      necrotic cell death in CV-A16-infected SK-N-SH cells, compared with EV-A71
      infected SK-N-SH cells, is consistent with the lower prevalence of neurotropism
      observed in CV-A16-associated HFMD outbreaks. Nonetheless, in vivo data and more
      extensive comparisons of different viral strains are essential to confirm our
      findings.

PMID- 27878461
TI  - Crimean-Congo hemorrhagic fever among children in Iran.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a viral zoonotic disease which is
      endemic in Iran. The etiological agent of CCHF is an RNA virus belonging to the
      genus Nairovirus of the family Bunyaviridae. CCHF virus (CCHFV) can be
      transmitted to humans through bites from infected ticks and direct contact with
      infected blood or tissues. Although the disease has been observed in different
      age groups, the rate of disease is lower in children and elderly. This study was
      designed to characterize CCHFV-infected children in Iran. Between 2000 and 2016,
      a total of 908 CCHF suspected cases (in children less than 19 years old) were
      evaluated for CCHFV infection by CCHF IgM ELISA and RT-PCR. CCHFV infection was
      observed in 161 (17.73%) of subjects. Most CCHF positive children were male
      (70.8%) and >15 years of age (65.8%). Contact with livestock was the main risk
      factor (35.4%). Sistan and Baluchestan provinces had the highest frequency within
      the infected cohort (68.3%). The overall mortality rate was 11.8%. This study
      also revealed a significant reduction in CCHF-fatality rates in Iranian children
      when compared to earlier studies in Iran. Having contact with livestock was the
      major risk factor and CCHF was more common in male children of an older age.

PMID- 27878463
TI  - Tracking of the inferior alveolar nerve: its implication in surgical planning.
AB  - OBJECTIVES: The objective of the study is to assess the correlation between the
      mandibular canal tracing done on cone beam CT (CBCT) data, with the size, shape,
      and position of the neurovascular bundle (NB) obtained by magnetic resonance
      imaging (MRI). MATERIAL AND METHODS: Six human cadaver mandibles were scanned
      with a CBCT Promax(r) scanner (Planmeca, Helsinki, Finland) and with an
      Ingenia(r) 3.0 T MR system (Philips, Amsterdam, The Netherlands). The NB was
      segmented from the MRI dataset, while the mandibular canal (MC) tracing was done
      on the CBCT images. Quantitative 3D analysis was made for the full-segmented
      nerves and for three defined regions of specific clinical interest, namely angle,
      body, and mental region. RESULTS: From the 3D MRI analysis, the nerve thickness
      (for the angle, body, and mental region) ranges from 0.8 to 5.2 mm, while the
      thickness of the mandibular canal tracing is approximately 2.00 mm on both sides
      as chosen in the tracing software. The mean volume of the NB on the left is
      828.49 +/- 215.54 mm3 and on the right 792.98 +/- 264.57 mm3. For the nerve
      tracing, the mean value is 351.92 +/- 16.42 and 339.69 +/- 16.12 mm3 on the left
      and right sides, respectively. Wilcoxon signed-rank test showed significant
      differences between NB and MC volume measurements (p = 0.0005). The Bland-Altman
      plots show an increasing slope for thickness and volume, indicating that the
      absolute differences between neurovascular bundle, estimated by MRI, and the
      mandibular canal, drawn on the CBCT images, increase with larger mean values.
      CONCLUSIONS: Surgeons should be aware of the shortcomings of nerve tracing in the
      different regions of the mandible. CLINICAL RELEVANCE: Tracing of the inferior
      alveolar nerve (IAN) underestimates shape and volume. Whenever nerve tracing
      instead of well-recognizable anatomical bony landmarks is used for surgical
      planning that need precision, a wider safe margin is recommended.

PMID- 27878465
TI  - Dr. T. S. Chandrasekar, incoming president, Indian Society of Gastroenterology
      2016-2017.

PMID- 27878464
TI  - Impact of abutment material on peri-implant soft tissue color. An in vitro study.
AB  - OBJECTIVES: The objectives of the present study is to determine the differences
      in peri-implant soft tissue color with the utilization of titanium, titanium gold
      plated, white zirconia, Vita Classical (VC) A4-shaded zirconia, and fluorescent
      white zirconia abutments and to establish the influence of gingival thickness on
      the resulting color. METHODS: Four implants were contralaterally inserted in 19
      fresh pig mandibles, and the color of the peri-implant mucosa with the different
      abutments was spectrophotometrically measured at 1-, 2-, and 3-mm height from the
      margin. RESULTS: At 1-mm height, titanium significantly differed from all
      zirconia abutments in lightness (L*), chroma along red axis (a*), and chroma
      along yellow-blue axis (b*) parameters. At 2 mm, all zirconia abutments differed
      from titanium in b* but only fluorescent zirconia in a*. At 3 mm, titanium
      differed from VC A4-shaded and fluorescent zirconia abutments in b*. At soft
      tissue thicknesses <1 and 1-2 mm, titanium differed from fluorescent zirconia in
      a* and b* and from VC A4-shaded zirconia in b*; at thickness >2 mm, no
      differences were found among abutments. All abutments differed from natural teeth
      in a* and b* at all heights and thicknesses except for fluorescent zirconia at
      thickness >2 mm. The Euclidean distance (DeltaEpsilon) differed between titanium
      abutments and gold, VC A4, and fluorescent zirconia at <1- and 1-2-mm
      thicknesses. CONCLUSION: The natural gingival color was not reproduced with any
      abutment at gingival thicknesses <2 mm. The worst color match was with titanium
      abutments and the best with fluorescent zirconia, followed by VC A4-shaded
      zirconia. At gingival thicknesses >2 mm, no differences were detected among
      abutments. CLINICAL RELEVANCE: This study demonstrates that the type of abutment
      and the gingival thickness affect the resulting peri-implant gingival color.

PMID- 27878466
TI  - Pancreatic exocrine insufficiency: Comparing fecal elastase 1 with 72-h stool for
      fecal fat estimation.
AB  - INTRODUCTION: Identification of pancreatic exocrine insufficiency (PEI) is
      important in the management of chronic pancreatitis. The 72-h stool for fecal fat
      estimation (FFE) has long been considered a gold standard indirect test for the
      diagnosis of PEI. However, the test is cumbersome for both patients and
      laboratory personnel alike. In this study, we aimed to assess fecal elastase 1
      (FE1) as an alternate to FFE for the diagnosis of PEI. METHODS: In all, 87
      consecutive patients diagnosed with chronic pancreatitis were included in this
      study. FFE and FE1 estimation was done for all the patients. For FE1, two cutoffs
      (<100 and <200 MUg) were selected to define pancreatic exocrine insufficiency.
      The sensitivity, specificity, and positive and negative predictive values for the
      two cutoffs were estimated. Kappa statistics was used to assess degree of
      agreement between both tests. RESULTS: All patients completed the study and were
      included in the analysis. The sensitivity, specificity, and positive and negative
      predictive value and PABAK (prevalence and bias adjusted kappa) for FE1 <100 MUg
      was 84.9, 47.6, 83.6, 50, and 0.52, respectively. For FE1 <200 MUg, it was 90.9,
      9.5, 75.95, 25, and 0.43, respectively. CONCLUSION: FE1 is a sensitive test;
      however, it does not have a good agreement with FFE. FE1 may be used as screening
      test for PEI in patients with chronic pancreatitis.

PMID- 27878467
TI  - Outcomes of retesting BRCA negative patients using multigene panels.
AB  - The utility of multigene panels in retesting patients who previously tested
      negative for a pathogenic mutation by BRCA1/2 testing is not well established.
      Patients who previously tested negative for a pathogenic BRCA1/2 mutation by
      standard sequencing, and who were seen in cancer genetics center between November
      1, 2012 and June 30, 2015 for additional testing utilizing multigene panels, were
      identified using our genetic testing registry. Data on demographics, personal and
      family history of cancer, results of panel testing and the impact on patient
      management was collected retrospectively. A total of 122 patients underwent
      retesting during the study period. Thirteen (11%) pathogenic mutations were
      identified in the following genes: CHEK2(4), PALB2(3), ATM(2), CDH1, APC, BARD1
      and MRE11A. Eleven out of these thirteen mutations were deemed actionable based
      on published guidelines. Of these eleven, seven patients had an actual change in
      clinical management as a result of retesting. Furthermore, retesting also led to
      a change in clinical management in the two patients with mutations in genes
      (BARD1 and MRE11A) which do not have clear guidelines for management. There were
      no significant differences in demographics and personal and family history of
      cancer between patients who tested positive and those who tested negative on
      retesting. This study demonstrates the clinical utility of multigene panels in a
      group of high risk individuals who previously tested negative for a BRCA1/2
      mutation. This retesting approach revealed a pathogenic mutation in 11% of cases.
      Retesting led to significant change in clinical management in a majority of
      patients with actionable mutations (7 out of 11), as well as in those with
      mutations in genes which do not have specific management guidelines.

PMID- 27878468
TI  - The Risk of Adverse Pregnancy Outcome After First Trimester Exposure to H1
      Antihistamines: A Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: H1 antihistamines are used for the treatment of nausea and vomiting
      during pregnancy as well as the symptomatic relief of asthma, urticaria, allergy,
      and the common cold. Although they are overall felt to be safe during pregnancy,
      recently several studies have challenged this assumption, as millions of women
      are exposed to them in the first trimester. METHODS: Following the guidelines of
      PRISMA, a systematic review was performed to retrieve all published articles
      involving H1-antihistamine exposure during pregnancy. Electronic databases
      including PubMed and EMBASE were searched for possibly relevant articles
      published in any language up to December 2015. RESULTS: After removing duplicate
      publications, and excluding animal studies and studies on drug effectiveness, 342
      articles were reviewed in detail and 37 studies fulfilled the inclusion criteria
      for the meta-analysis. In cohort studies, the risk of major malformation in the
      offspring of women exposed to H1 antihistamines was not higher than that of the
      control population (OR 1.07; 95% CI 0.98-1.16). The Q-statistic for heterogeneity
      of effects was not significant (p > 0.05, I 2 < 25%) and there was no evidence of
      publication bias. Similar results were achieved with case-control studies (OR
      1.05; 95% CI 0.90-1.23). Similarly, H1 antihistamines were not associated with
      more spontaneous abortions (OR 1.00; 95% CI 0.83-1.20), prematurity (OR 0.96; 95%
      CI 0.76-1.20), stillbirth (OR 1.23; 95% CI 0.48-3.18) or low birth weight (OR
      1.20; 95% CI 0.63-2.29). CONCLUSIONS: Based on our meta-analyses, which included
      a large number of studies, H1 antihistamines are not associated with an increased
      risk of major malformation or other adverse fetal outcomes. This study provides
      important information to both pregnant women and their healthcare providers
      regarding the safety and risk of H1 antihistamine use during this sensitive time.

PMID- 27878469
TI  - Genetic diversity and population structure of Nuphar submersa (Nymphaeaceae), a
      critically endangered aquatic plant endemic to Japan, and implications for its
      conservation.
AB  - Nuphar submersa (Nymphaeaceae) is a critically endangered freshwater macrophyte
      indigenous to central Japan, with only four small extant populations represented
      across its entire range. We investigated the genotypic and genetic diversity as
      well as the genetic structure of all extant individuals of N. submersa based on
      analysis of 15 microsatellite loci. Among 278 individual ramets, 52 multilocus
      genotypes were detected: 30 genotypes in Nikko City (NIK), 18 in Nasukarasuyama
      City (NAS), 3 in Mooka City (MOK), and 1 in Sakura City (SAK). The average number
      of alleles per locus ranged from 1.20 to 1.93, whereas the observed and expected
      heterozygosities ranged from 0.11 to 0.33 and from 0.10 to 0.24, respectively.
      With the exception of SAK, all populations contained multiple clones, but our
      results indicated low levels of within-population genetic diversity. The
      populations NIK and NAS comprised few large or middle-sized genets and many small
      genets. The populations NIK and NAS were suggested to comprise large old, old
      fragmented, and/or young small genets resulting from seedling establishment. All
      four populations were differentiated, and gene flow between the populations was
      restricted (average level of gene flow (Nm) = 0.122, G' ST  = 0.639). Of the
      total genetic diversity, 67.20 and 9.13% were attributable to inter- and intra
      population diversity, respectively. STRUCTURE analysis revealed two or three well
      differentiated groups of populations. Cluster I comprised one population (NIK)
      and cluster II comprised the remaining populations at K = 2. The populations NIK,
      NAS, and the remaining populations were assigned to clusters I, II, and III,
      respectively, at K = 3. For conservation practices, we recommend that each
      cluster be regarded as a different management unit. We further suggest that
      artificial gene flow among MOK and SAK populations is an appropriate option,
      whereas NIK should not be reinforced with genotypes from the remaining
      populations.

PMID- 27878472
TI  - CanMEDS is a theory.

PMID- 27878471
TI  - Cerebrospinal fluid anti-Epstein-Barr virus specific oligoclonal IgM and IgG
      bands in patients with clinically isolated and Guillain-Barre syndrome.
AB  - Epstein-Barr virus (EBV) has been implicated in multiple sclerosis (MS)
      pathogenesis. We aimed to assess the frequency of EBV-specific IgG and IgM
      oligoclonal bands (OCB) in cerebrospinal fluid (CSF) of 50 patients with
      clinically isolated syndrome (CIS) and in 27 controls with Guillain-Barre
      syndrome (GBS). Furthermore, we assessed correlations between the presence of OCB
      and CIS patients' CSF, MRI, and clinical variables. There was no difference in
      the proportion of CIS and GB patients with positivity for anti-EBV-specific
      IgG/IgM OCB. There were no correlations between OCB and analyzed variables, nor
      were they predictive of a higher disability at 3 years.

PMID- 27878470
TI  - beta2 Agonists.
AB  - History suggests beta agonists, the cognate ligand of the beta2 adrenoceptor,
      have been used as bronchodilators for around 5,000 years, and beta agonists
      remain today the frontline treatment for asthma and chronic obstructive pulmonary
      disease (COPD). The beta agonists used clinically today are the products of
      significant expenditure and over 100 year's intensive research aimed at
      minimizing side effects and enhancing therapeutic usefulness. The respiratory
      physician now has a therapeutic toolbox of long acting beta agonists to
      prophylactically manage bronchoconstriction, and short acting beta agonists to
      relieve acute exacerbations. Despite constituting the cornerstone of asthma and
      COPD therapy, these drugs are not perfect; significant safety issues have led to
      a black box warning advising that long acting beta agonists should not be used
      alone in patients with asthma. In addition there are a significant proportion of
      patients whose asthma remains uncontrolled. In this chapter we discuss the
      evolution of beta agonist use and how the understanding of beta agonist actions
      on their principal target tissue, airway smooth muscle, has led to greater
      understanding of how these drugs can be further modified and improved in the
      future. Research into the genetics of the beta2 adrenoceptor will also be
      discussed, as will the implications of individual DNA profiles on the clinical
      outcomes of beta agonist use (pharmacogenetics). Finally we comment on what the
      future may hold for the use of beta agonists in respiratory disease.

PMID- 27878473
TI  - Education and neuroscience.

PMID- 27878474
TI  - Quantitative Assessment of CYP2C9 Genetic Polymorphisms Effect on the Oral
      Clearance of S-Warfarin in Healthy Subjects.
AB  - BACKGROUND: Genetic polymorphisms in CYP2C9 account for 10-20% of the variability
      in warfarin dose requirement. As such CYP2C9 genetic polymorphisms are commonly
      included in algorithms aimed to optimize warfarin therapy as a way to account for
      variability in warfarin responsiveness that is due to altered pharmacokinetics.
      However, most of the currently available pharmacokinetic data were derived from
      studies among patients on chronic warfarin therapy and therefore suffer from the
      confounding effects of disease states and drug interactions. OBJECTIVE: The
      purpose of the present study was to provide an accurate quantitative estimate of
      S-warfarin oral clearance (CLS) among healthy subjects carrying different CYP2C9
      genotypes. METHODS: Single dose of warfarin was administered to 150 non-smokers,
      age (mean +/- SD) 23.3 +/- 4.5 years, 60% male, non-obese, healthy subjects.
      Blood samples were taken for up to 168 h and urine was collected over the entire
      study period. RESULTS: Compared with carriers of the wild-type CYP2C9*1/*1
      genotype (n = 69), CLS was reduced by 25, 39 and 47% among heterozygote for
      CYP2C9*2 (n = 41) CYP2C9*3 (n = 26) and carriers of 2 variant alleles (n = 14),
      respectively (p < 0.001). The corresponding decrease in the formation clearance
      of 6 and 7 S-hydroxy-warfarin was 45, 65 and 75%, respectively (p < 0.001).
      CONCLUSIONS: The current study provides an estimate concerning the effect of
      CYP2C9 polymorphisms on S-warfarin pharmacokinetics among healthy subjects. As
      such it is free of the confounding effects of disease states and drug
      interactions. Further research is needed to evaluate whether the incorporation of
      quantitative data obtained in the present study into pharmacogenetic warfarin
      algorithm may enhance its precision. TRIAL REGISTRATION: Clinicaltrials.gov
      Identifier NCT00162474.

PMID- 27878477
TI  - Paraneoplastic Pemphigus and Autoimmune Blistering Diseases Associated with
      Neoplasm: Characteristics, Diagnosis, Associated Neoplasms, Proposed
      Pathogenesis, Treatment.
AB  - Autoimmune paraneoplastic and neoplasm-associated skin syndromes are
      characterized by autoimmune-mediated cutaneous lesions in the presence of a
      neoplasm. The identification of these syndromes provides information about the
      underlying tumor, systemic symptoms, and debilitating complications. The
      recognition of these syndromes is particularly helpful in cases of skin lesions
      presenting as the first sign of the malignancy, and the underlying malignancy can
      be treated in a timely manner. Autoimmune paraneoplastic and neoplasm-associated
      bullous skin syndromes are characterized by blister formation due to an
      autoimmune response to components of the epidermis or basement membrane in the
      context of a neoplasm. The clinical manifestations, histopathology and
      immunopathology findings, target antigens, associated neoplasm, current
      diagnostic criteria, current understanding of pathogenesis, and treatment options
      for a selection of four diseases are reviewed. Paraneoplastic pemphigus manifests
      with clinically distinct painful mucosal erosions and polymorphic cutaneous
      lesions, and is often associated with lymphoproliferative neoplasm. In contrast,
      bullous pemphigoid associated with neoplasm presents with large tense
      subepidermal bullae of the skin, and mild mucosal involvement, but without unique
      clinical features. Mucous membrane pemphigoid associated with neoplasm is a
      disorder of chronic subepithelial blisters that evolve into erosions and
      ulcerations that heal with scarring, and involves stratified squamous mucosal
      surfaces. Linear IgA dermatosis associated with neoplasm is characterized by
      annularly grouped pruritic papules, vesicles, and bullae along the extensor
      surfaces of elbows, knees, and buttocks. Physicians should be aware that these
      autoimmune paraneoplastic and neoplasm-associated syndromes can manifest distinct
      or similar clinical features as compared with the non-neoplastic counterparts.

PMID- 27878476
TI  - Management of Post-Liver Transplant Recurrence of Hepatitis C.
AB  - Cirrhosis due to chronic hepatitis C (HCV) is the leading indication for liver
      transplantation in North America and Europe. HCV re-infection post-transplant is
      nearly universal and if left untreated negatively affects patient and graft
      survival. Until recently, treatment options for HCV were limited to interferon
      (IFN)-based therapies which had low sustained viral response (SVR) rates and were
      poorly tolerated in the post-transplant setting. In the last 3 years, the promise
      of the directly acting antivirals (DAAs) for the treatment of HCV has been
      fulfilled with high sustained viral response (SVR) rates and a low side effect
      profile demonstrated in both registration trials and real-world studies. This
      innovation has allowed post-liver transplant patients with HCV recurrence access
      to interferon-free therapies with extraordinary efficacy, safety, tolerability,
      and fewer drug-drug interactions.

PMID- 27878475
TI  - Epigenetic Biomarkers in Colorectal Cancer.
AB  - Developments in the diagnosis and treatment of colorectal cancer (CRC) have been
      made in the last decade, but the overall survival rate of patients with CRC has
      not improved dramatically. Genetic and epigenetic events contribute to CRC
      pathogenesis. Tumor heterogeneity results in a range of prognoses and responses
      to CRC management and therapy. Epigenetic biomarkers have potential in CRC
      diagnosis and in measuring response to therapy. Combining information from
      genetic and epigenetic alterations provides an opportunity to predict response to
      therapy. Epigenetic biomarkers can be used in disease stratification, which also
      helps in designing therapeutic approaches for CRC. Challenges in the
      understanding of CRC development and gaps in knowledge are discussed.

PMID- 27878479
TI  - Total Transthoracic Approach Facilitates Laparoscopic Hepatic Resection in
      Patients with Significant Prior Abdominal Surgery.
AB  - BACKGROUND: While the oncologic safety of minimally invasive hepatectomy for
      colorectal liver metastases (CLM) has been demonstrated, lesions in the postero
      superior segments may be challenging.1 - 3 For these lesions, a transthoracic
      approach may be particularly helpful, especially in patients with a
      hostile/reoperative abdomen or morbid obesity.4 , 5 PATIENT: A 43-year-old man
      with a body mass index of 36.0 who had undergone rectosigmoid resection for
      primary cancer 5 years ago recurred with a solitary liver metastasis in SVIII. He
      had previously undergone the following resections for metachronous CLM: (i)
      partial resections of SV/VIII and SII/III; (ii) ablation for SVII; and (iii) left
      hepatectomy, common bile duct resection, and choledochojejunostomy. Following
      four cycles of FOLFIRI/panitumumab with good response, the patient was considered
      for his fourth abdominal cancer intervention via a thoracoscopic approach.
      TECHNIQUE: In a modified French position with left-lung ventilation, access to
      the right thoracic cavity was gained. Following thoracic adhesiolysis,
      transdiaphragmatic intraoperative ultrasonography (IOUS) was performed. To ensure
      optimal margins, IOUS-guided transthoracic hepatic resection with partial
      resection of the diaphragm was conducted. The diaphragm was reconstructed and a
      chest tube placed. Operative time was 247 min, with an estimated blood loss of
      100 mL. Postoperative recovery was uneventful; pathology demonstrated no viable
      tumor, with the closest margin 5 mm from the necrotic area. CONCLUSION:
      Transthoracic hepatic resection of SVIII can optimize the port-target axis while
      minimizing morbidity. A systematic approach that includes precise port
      positioning, non-traumatic intrathoracic adhesiolysis, and meticulous
      transdiaphragmatic IOUS-guided parenchymal transection can optimize outcomes.

PMID- 27878478
TI  - Liver Resection After Selective Internal Radiation Therapy with Yttrium-90 is
      Safe and Feasible: A Bi-institutional Analysis.
AB  - BACKGROUND: Treatment with yttrium-90 (Y90) microspheres has emerged as a viable
      liver-directed therapy for patients with unresectable tumors and those outside
      transplantation criteria. A select number of patients demonstrate a favorable
      response and become candidates for surgical resection. METHODS: Patients who
      underwent selective internal radiation therapy (SIRT) with Y90 microspheres at
      two institutions were reviewed. Patients who underwent liver resection were
      included in the study. The data gathered included demographics, tumor
      characteristics, response to Y90, surgical details, perioperative outcomes, and
      survival. RESULTS: The inclusion criteria were met by 12 patients. The diagnoses
      included metastatic disease from colorectal adenocarcinoma (n = 6),
      neuroendocrine tumor (n = 1), and ocular melanoma (n = 1) in addition to
      hepatocellular carcinoma (n = 4). The median time from liver disease diagnosis to
      Y90 treatment was 5.5 months (range 2-92 months). The median time from Y90
      treatment to surgery was 9.5 months (range 3-20 months). The surgical approach
      included right hepatectomy (n = 3), extended right hepatectomy (n = 5), extended
      left hepatectomy (n = 1), segmentectomy with ablation (n = 2), and segmentectomy
      with isolated liver perfusion (n = 1). The hospital stay was 7 days (range 4-31
      days), and 67% of the patients were discharged home. The readmission rate was
      42%. The 90-day morbidity and mortality rates were respectively 42 and 8%. At
      this writing, the median overall survival has not been reached at 25 months.
      CONCLUSION: Liver resection after Y90 SIRT is a challenging surgical procedure
      with high rates of perioperative morbidity and hospital readmission. However, for
      properly selected patients, potential exists for extending disease-free and
      overall survival in the current era of multimodal therapy for malignant liver
      disease.

PMID- 27878480
TI  - Management for Peritoneal Metastasis of Colonic Origin: Role of Cytoreductive
      Surgery and Perioperative Intraperitoneal Chemotherapy: A Single Institution's
      Experience During Two Decades.
AB  - BACKGROUND: Peritoneal metastasis of colonic origin is associated with a poor
      prognosis. This study aimed to analyze the clinicopathologic characteristics and
      prognostic predictors of survival in a cohort of patients treated with
      cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (POIC)
      during two decades. METHODS: A retrospective study analyzed a prospectively
      maintained database for all patients treated for peritoneal metastasis of a
      colonic origin (PCC) from January 1990 to April 2015. RESULTS: The 318 patients
      in our study comprised 171 men (53.8%) and 147 women (46.2%). The mean age of the
      patients at presentation was 50.6 years, (range 18-86 years). Overall survival
      was 42.5%, median survival and follow-up time was 21.5 and 15.0 months
      respectively. The 3 and 5 years survival rates were respectively 35 and 25%. The
      median survival time was 20.6 months for the men and 23.1 months for the women (p
      = 0.14). The mean intraoperative peritoneal carcinomatosis index (PCI) was 15.2.
      The patients who had a completeness of cytoreduction (CC) score of 0 or 1 (no
      residual disease <0.25 mm) had a median survival time of 36.6 months compared
      with 18.3 months for the patients with a CC-2 score and 7.6 months for the
      patients with a CC-3 score (p < 0.000). The significant independent predictors of
      survival in the multivariate analysis were the CC score and elevated tumor makers
      CA153 and CA125. CONCLUSION: For patients with a limited extent of peritoneal
      metastases, CC is the most important prognostic variable for improved survival of
      colon cancer patients with peritoneal metastases.

PMID- 27878481
TI  - Field investigations of dissipations and residues of cyazofamid in soil and
      tomato: risk assessment of human exposure to cyazofamid via tomato intake.
AB  - Cyazofamid, as a fungicide of the novel cyanoimidazole chemical class, has been
      widely used to control tomato late blight. Understanding of cyazofamid residues
      in environment and crops is an essential prerequisite for its risk assessment. In
      this study, field investigations in four typical tomato-producing areas were
      conducted to explore the dissipation kinetics and residues of cyazofamid and its
      primary metabolite 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM) in soil and
      tomato. A robust method using QuEChERS coupled with liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) was developed for simultaneous analysis of
      cyazofamid and CCIM, with limits of quantification of 0.33 and 3.8 MUg/kg,
      respectively. Field trials showed that the half-lives of cyazofamid were 3.6-6.9
      days in soil and 12.2-18.3 days in tomato. The total residues of cyazofamid and
      CCIM in tomato collected at three time intervals were all below 0.5 mg/kg.
      Moreover, the potential risks of total residues via tomato intake to ten
      population subgroups were evaluated. We found that the risk quotient values were
      all generally low (0.13-1.3%), indicating that the recommended dose of cyazofamid
      on tomato will not result in a consumer exposure exceeding the toxicological
      reference value. Here, the results of field investigation provided important
      information for further understanding the behavior and risk of cyazofamid in the
      natural environment.

PMID- 27878484
TI  - Pilot scale nanofiltration treatment of olive mill wastewater: a technical and
      economical evaluation.
AB  - The treatment of large volumes of olive mill wastewater is presently a challenge.
      This study reports the technical and economical feasibility of a sequential
      treatment of olive mill wastewater comprising a dissolved air flotation pre
      treatment and nanofiltration. Different pilot nanofiltration assays were
      conducted in a concentration mode up to different volume reduction factors (29,
      45, 58, and 81). Data attained demonstrated that nanofiltration can be operated
      at considerably high volume reduction factors and still be effective towards the
      removal of several components. A flux decline of approximately 50% was observed
      at the highest volume reduction factor, mainly due to increase of the osmotic
      pressure. Considerably high rejections were obtained across all experiments for
      total suspended solids (83 to >99%), total organic carbon (64 to 99%), chemical
      oxygen demand (53 to 77%), and oil and grease (67 to >82%). Treated water was in
      compliance with European legal limits for discharge regarding total suspended
      solids and oil and grease. The potential recovery of phenolic compounds was
      evaluated and found not relevant. It was demonstrated that nanofiltration is
      economically feasible, involving operation costs of approximately 2.56-3.08 ?/m3,
      depending on the working plan schedule and volume reduction factor, and requiring
      a footprint of approximately 52 m2 to treat 1000 m3 of olive mill wastewater.

PMID- 27878482
TI  - An in-vitro approach for water quality determination: activation of NF-kappaB as
      marker for cancer-related stress responses induced by anthropogenic pollutants of
      drinking water.
AB  - Epidemiological studies show that there is a link between urban water pollution
      and increase in human morbidity and mortality. With the increase in number of new
      substances arising from the chemical, pharmaceutical, and agricultural
      industries, there is an urgent need to develop biological test systems for fast
      evaluation of potential risks to humans and the environmental ecosystems. Here, a
      combined cellular reporter assay based on the cellular survival and the stress
      induced activation of the survival-promoting factor nuclear factor kappaB (NF
      kappaB) and its use for the detection of cytotoxicity and cancer-related stress
      responses is presented. A total of 14 chemicals that may be found in trace
      amounts in ground water levels are applied and tested with the presented assay.
      The project is embedded within the joint research project TOX-BOX which aims to
      develop a harmonized testing strategy for risk management of anthropogenic trace
      substances in potable water. The assay identified carbendazim as a NF-kappaB
      activating agent in mammalian cells.

PMID- 27878483
TI  - Fine particulate-bound polycyclic aromatic hydrocarbons in vehicles in Rome,
      Italy.
AB  - Urban commuters are exposed to elevated levels of air pollutants, especially in
      heavily polluted areas and traffic congested roads. In order to assess the
      contribution of commuting to citizens' exposure, measurements of fine particulate
      (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) were carried out in cars,
      busses, and metro trains, within the LIFE+ EXPAH Project. Monitoring campaigns
      were performed in Rome, Italy, from April 2011 to August 2012. Inside the busses,
      the concentration of total PAHs ranged from 2.7 to 6.6 ng/m3 during the winter
      and from 0.34 to 1.51 ng/m3 in the summer. In cars, internal concentrations were
      in the range 2.2-7.3 and 0.46-0.82 ng/m3, respectively, in the 2-year time.
      Analogous differences between seasons were observed examining the benzo[a]pyrene
      equivalent carcinogenicity. In the metro trains, total PAHs ranged from 1.19 to
      2.35 ng/m3 and PM2.5 ranged from 17 to 31 MUg/m3. The PM2.5 concentration in all
      transport modes ranged from 10 to 160 MUg/m3 during the cold season and 15-48
      MUg/m3 during the warm time. The average inside-to-outside ratio (R I/O) was
      found to exceed 1.0 for PM2.5 only in busses, probably due to dust re-suspension
      caused by crowding and passenger activity. The molecular PAH signature suggests
      that vehicle emissions and biomass combustion were the major sources of
      commuters' exposure to these toxicants in Rome. According to linear regression
      analysis, the PAH concentrations inside the vehicles were linked to those
      detected outside. Statistically significant differences (p < 0.05) were found
      between the in-vehicle locations and the urban pollution network stations, with
      higher PAH values detected, on the average, in these latter.

PMID- 27878485
TI  - Biofilms in bioremediation and wastewater treatment: characterization of
      bacterial community structure and diversity during seasons in municipal
      wastewater treatment process.
AB  - The bacterial community structure and diversity were assessed at the scale of
      rotating biodisk procedure (RB) in a semi-industrial pilot plant. As well, the
      Salmonella community was particularly monitored, and the effects of ultraviolet
      (UV-C254) on the bacterial community were studied. The identification of dominant
      bacteria revealed the presence of beneficial and useful species that could play
      an important role in the process of wastewater purification. Several species as
      Enterobacter agglomerans, Cronobacter sakazakii, and Pantoea agglomerans known
      for their bioremediation activities were revealed in the majority of biofilm
      samples. Common detection of Salmonella community provides evidence that the RB
      system did not seriously affect Salmonella. Furthermore, the investigation on the
      (UV)-C254 inactivation of the whole bacterial community, in secondary treated
      wastewater, showed variable UV resistance results. No Salmonella detection was
      registered at a dose of around 1440 mW s cm-2 since a total disappearance of
      Salmonella was recorded.

PMID- 27878488
TI  - Peculiar Aspects in Influence of alpha1-Adrenoceptor Stimulation on Isolated Rat
      Heart.
AB  - The study examined the effect of alpha1-adrenoceptor stimulation with methoxamine
      on chronotropic function of isolated heart perfused ex vivo according to
      Langendorff and cardiac chronotropy in vivo. Stimulation of alpha1-adrenoceptors
      in isolated heart induced gradually developing bradycardia, which progressed
      during several minutes. Similar stimulation in vivo produced a short-term
      bradycardia probably terminated by the compensatory influences in the whole
      organism. Comparison of the data obtained in both experimental paradigms during
      alpha1-adrenoceptor stimulation revealed unidirectional changes in cardiac
      chronotropy characterized with time-related peculiarities.

PMID- 27878486
TI  - Assessment of questionnaire-based PCB exposure focused on food frequency in birth
      cohorts in Japan.
AB  - We investigated the relationship between food frequency questionnaire (FFQ)
      responses and serum polychlorinated biphenyl (PCB) levels of mothers and fathers
      recruited from the Chiba Regional Center, which is one of the 15 regional centers
      of the Japan Environment and Children's Study (mothers: n = 1477, fathers: n =
      219). The expected PCB values were estimated from the participants' FFQ answers
      and medical records (age, body mass index and number of deliveries). Based on the
      stepwise forward selection results of Bayesian regression models, age and fish
      and egg consumption were positively associated with PCB concentrations and a
      number of deliveries were negatively associated with PCB concentrations in
      mothers, whereas only age was positively associated with PCB concentrations in
      fathers.These findings indicated that the estimation of daily dietary intake may
      be useful for the prediction of PCB concentration for mothers.

PMID- 27878487
TI  - Paradoxical Effect of NMDA Receptor Blockade in Chicks on Learning and Memory in
      Passive Avoidance Model.
AB  - Activity of NMDA receptors is a prerequisite for numerous but not all forms of
      neuronal plasticity and learning. The present study examined the role of NMDA
      receptors in standard, weak, and repeated passive avoidance training in young
      chicks. Injection of MK-801, an antagonist of NMDA receptor, prior to strong
      training episode impaired subsequent memory recall. Moreover, repeated training
      did not restore the lost memory. In the double weak training protocol, the
      impairing effect of MK-801 was observed only when it was injected prior to the
      second but not to the first training episode. These results suggest that
      activation of NMDA receptors is not a necessary stage for memory acquisition in
      the weak training task. In contrast, the mechanisms of strong training depending
      on activation of NMDA receptors can be probably involved into the second training
      episode performed against the background of existing NMDA receptor-independent
      memory about the first training episode.

PMID- 27878490
TI  - Cardiac Body Surface Potentials in Rats with Experimental Pulmonary Hypertension
      during Ventricular Depolarization.
AB  - The spatial and the amplitude-temporal parameters of cardiac body surface
      potentials were examined in female Wistar rats with experimental pulmonary
      hypertension during ventricular depolarization. The cardiac body surface
      potentials have been led from 64 subcutaneous electrodes evenly distributed
      across the chest surface prior to and 4 weeks after subcutaneous injection of a
      single dose of monocrotaline (60 mg/kg). Right ventricular hypertrophy and
      electrophysiological remodeling of the heart developed in rats with experimental
      pulmonary hypertension in 4 weeks after monocrotaline injection; these changes
      led to a significant increase in amplitude and temporal characteristics of the
      cardioelectric field on the body surface in comparison with the initial state.

PMID- 27878489
TI  - Pro- and Antioxidant Systems in the Lower Portion of Rat Brainstem during
      Hydroxybutyrate-Induced Pathological Periodic Breathing.
AB  - Activities of superoxide dismutase and catalase characterizing antioxidant status
      of the nervous tissue and its resistance to free radical oxidation were measured
      in the brainstem of rats with hydroxybutyrate-induced pathological periodic
      breathing. Hydroxybutyrate modified the pro- and antioxidant status in the
      brainstem respiratory center. It markedly inhibited catalase activity; in rats
      without the signs of periodic breathing, hydroxybutyrate up-regulated superoxide
      dismutase activity and to a lesser extent increased the resistance of the
      membrane structures in the medulla oblongata to induction of free radical
      oxidation. In rats with periodic breathing pattern, hydroxybutyrate induced more
      pronounced increase in the sensitivity of membrane structures in the medulla
      oblongata to induction of free radical oxidation.

PMID- 27878491
TI  - Possible Cause of Nonlinear Tension Rise in Activated Muscle Fiber during
      Stretching.
AB  - Tension in contracting muscle fiber under conditions of ramp stretching rapidly
      increases, but after reaching a critical stretch Pc sharply decreases. To find
      out the cause of these changes in muscle fiber tension, we stopped stretching
      before and after reaching Pc and left the fiber stretched for 50 msec. After
      rapid tension drop, the transient tension rise not accompanied by fiber stiffness
      increase was observed only in fibers heated to 25 degrees C and stretched to Pc.
      Under other experimental conditions, this growth was absent. We suppose that
      stretch of the fiber to Pc induces transition of stereo-specifically attached
      myosin heads to pre-power stroke state and when the stretching is stopped, they
      make their step on actin and generate force. When the tension reaches Pc, all
      stereospecifically attached myosin heads turn out to be non-stereospecifically,
      or weakly attached to actin, and are unable to make the force-generating step.

PMID- 27878492
TI  - Collagen-1 Membrane for Replacing the Bladder Wall.
AB  - We studied the possibility of using membrane fabricated from type 1 collagen
      isolated from cattle tissues (group 1) or porcine tissues (group 2) for
      replacement of the resected bladder wall defect in rabbits in order to retain
      functional volume of the organ. Satisfactory take of both types of collagen
      membranes with formation of competent anastomosis was observed. Histological
      studies revealed inflammatory process in the bladder wall at the site of contact
      with the implanted membrane (more pronounced in case of membranes from cattle
      tissues) that decreased by day 21 of the experiment. Bladder tissue ingrowth into
      the implant from was observed starting from day 14. The bladder capacity
      decreased in 7 days after surgery in both groups, presumably because of
      increasing tone of the organ wall resulting from surgical trauma and
      inflammation. In group 2, the bladder volume increased by day 14 after surgery
      and returned to normal by day 21, whereas in group 1 it remained below the
      control despite a trend to increase. These findings confirm good prospects of
      using collagen-1 membranes for plastic repair of the urinary bladder, the
      membranes from porcine collagen being more preferable.

PMID- 27878493
TI  - Enzymatic Sensor Detects Some Forms of Nitric Oxide Donors Undetectable by Other
      Methods in Living Tissues.
AB  - Studies with the use of highly sensitive enzymatic sensor have shown the presence
      of various forms of nitrosyl iron complexes, including those undetectable by
      other methods, in living tissues. All these complexes are long-living compounds
      and constitute the major part of nitroso compounds in the blood, muscles, liquor,
      and amniotic fluid.

PMID- 27878494
TI  - 2-Morpholino-5-Phenyl-6H-1,3,4-Thiadiazine Corrects Metabolic Disorders during
      the Development of Alloxan Diabetes Mellitus in Rats.
AB  - Metabolic disorders were evaluated in rats with alloxan diabetes mellitus after
      administration of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine (compound L-17).
      Administration of L-17 reduced the severity of metabolic disorders associated
      with diabetes mellitus. At the end of the experiment, the concentration of
      glucose, glycated hemoglobin, malonic dialdehyde, and catalase activity were
      significantly higher and peroxidase activity was significantly lower in the group
      of animals receiving L-17. The decrease of glycemia, glucose concentration, and
      glycated hemoglobin content was reached by the 3rd-4th week of the experiment.
      These data suggest that correction of biochemical parameters in rats with alloxan
      diabetes was reached after administration of L-17 for at least 3 weeks.

PMID- 27878495
TI  - Evaluation of Hemodynamic Significance of Stenosis in Multiple Involvement of the
      Coronary Vessels by Mathematical Simulation.
AB  - We use a mathematical model of one-dimensional blood flow in a network of blood
      vessels for in silico evaluation of hemodynamic significance of stenoses in
      multivessel coronary disease. Two cases were addressed: two stenosed vessels with
      different diameters and with the same degree of occlusion and two consecutive
      stenoses in the same vessel. We show that two criteria for the evaluation of
      hemodynamic significance based on the degree of stenosis and based on fractional
      flow reserve can give contradictory indications for surgical intervention. We
      also show that fractional flow reserve computation originally proposed for a
      single stenosis should be modified in the case of multivessel stenotic disease.

PMID- 27878496
TI  - Effect of Natural and 24-h Illumination on Mesenchymal Stem Cells.
AB  - We studied the effect 24-h illumination on quantitative and qualitative
      parameters of the bone marrow cells in Wistar rats. It was shown that
      desynchronosis reduced the release of nucleated cells from the femoral bone,
      while melatonin weakened this effect. The number of bone marrow mesenchymal
      stromal cells was resistant to circadian rhythm disturbances, while proliferation
      depended on glucose concentration in the medium.

PMID- 27878497
TI  - Role of Tissue-Specific Stem and Progenitor Cells in the Regeneration of the
      Pancreas and Testicular Tissue in Diabetic Disorders.
AB  - Using the model of hypogonadism in C57Bl/6 male mice, we showed that injection of
      streptozotocin to newborn animals and high-fat diet induced serum IFN-gamma and
      IL-17 elevation, glucose metabolism disturbances, insulin resistance, destructive
      changes of the Langerhans islets (deficit of PDX1+beta cells), while the number
      of oligopotent beta cell precursors (CD45-TER119-CD133+CD49flow) increased.
      Diabetes played the role of an inducer of testicular tissue inflammation (pan
      hemopoietic cell infiltration, increase of IL-2, IL-17, and IL-23 content) and
      reproductive system disturbances in mice (decrease in free testosterone
      concentration, suppression of spermatogenesis, and infertility). The development
      of hypogonadism was paralleled by an increase in the count of spermatogonial stem
      cells (CD117+CD29+CD90+), multipotent mesenchymal stromal cells (CD45-CD31
      CD90+CD106+), hemangiogenesis precursors (CD45-CD117+Flk1+), and epithelial cells
      (CD45-CD31-CD49f+CD326+).

PMID- 27878498
TI  - Stimulation of Diethylnitrosamine Metabolism Reduces Its General Toxic and
      Hepatocarcinogenic Effects.
AB  - The general toxic and hepatocarcinogenic effects of diethylnitrosamine after
      stimulation of its metabolism with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene
      (TCPOBOP) were studied. The hydroxylating activity of liver microsomes of
      C57Bl/6Mv mice towards p-nitrophenol increased more than 4-fold 3 days after
      injection of TCPOBOP. Injection of diethylnitrosamine 3 days after TCPOBOP caused
      a lesser body weight loss and decrease of food consumption in C57Bl/6Mv mice than
      in response to diethylnitrosamine without preinduction. Injection of
      diethylnitrosamine to suckling ICR mice after TCPOBOP induction of cytochrome
      P450 2e1 activity led to development of 2-fold lesser number of tumors and
      pretumorous nodes in the liver in comparison with animals injected with
      diethylnitrosamine without induction. These data indicated that metabolism
      stimulation reduced the general toxic and hepatocarcinogenic effects of
      diethylnitrosamine.

PMID- 27878499
TI  - Therapeutic potential of ADAM17 modulation in gastric cancer through regulation
      of the EGFR and TNF-alpha signalling pathways.
AB  - A disintegrin and metalloproteinase 17 (ADAM17) is highly expressed in various
      tumours and affects tumour progression. In this study, ADAM17 expression in 60
      gastric cancer and 20 normal gastric mucosal tissues was assessed using
      immunohistochemistry. ADAM17 expression was higher in gastric cancer tissues than
      in normal gastric mucosal tissues (P < 0.0005). A significant relationship was
      identified between ADAM17 expression and the depth of tumour invasion,
      metastasis, and carcinoma stage. Furthermore, the effects of ADAM17 knockdown on
      the proliferation, cell invasion, and apoptosis of human gastric carcinoma cells
      (SGC-7901) were determined. SGC-7901 cells were transfected with ADAM17-shRNA,
      and cell proliferation and migration were assessed using CCK-8 and transwell
      assays, respectively, to evaluate the role of ADAM17 in tumour proliferation and
      invasion. Furthermore, the EGFR signalling pathway, the cell membrane receptor
      bound TNF-alpha level, and apoptosis were evaluated by western blotting and flow
      cytometry. The inhibition of cell proliferation and invasion was observed in the
      ADAM17 knockdown cells, which was associated with modulation of the EGFR
      signalling pathway. Apoptosis was increased, and TNF-alpha signalling was
      attenuated in the ADAM17 knockdown cells. Our study demonstrated that ADAM17 over
      expression in gastric cancer tissues was closely associated with tumour
      proliferation, invasion, and apoptosis.

PMID- 27878500
TI  - Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic
      formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced
      arthritis.
AB  - Kerabala (CB) is a novel ayurvedic formulation used for treating various
      inflammatory diseases. This formulation was made from virgin coconut oil and it
      comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current
      study was performed to evaluate the anti-inflammatory action of CB on carrageenan
      induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was
      found to be potent dose from carrageenan model and evaluated its effect in
      adjuvant-induced chronic arthritic model. The antioxidant assays like SOD,
      catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and
      GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB)
      count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the
      inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide
      synthase (iNOS), tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6)
      expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP
      9 were determined by zymography and its expression by western blotting.
      Histopathology and cytology of paw tissue and synovium were analyzed. The result
      indicated that there was a significant increment in the levels of antioxidant
      enzymes on CB administration. The hematological markers such as ESR, WBC and
      plasma CRP levels were reduced by CB treatment and it also increases the HB
      level. The upregulated gene level expressions of inflammatory markers like COX-2,
      iNOS, TNF-alpha and IL-6 were down regulated by administration of CB. MMP-2 and
      MMP-9 expression significantly reduced by CB administration. Massive influx of
      inflammatory cell infiltration, proliferative collagen in histological analysis
      of paw tissue of arthritic rat was decreased by CB administration. Synovial
      cytology of CB administrated group shows reduced number of reactive mesothelial
      cells and synovial inflammatory cells. This current study shows that ayurvedic
      drug CB has an antioxidant, anti-inflammatory and anti-arthritic activity in
      experimental arthritic model. CB as an anti-arthritic drug has beneficial effect
      for treating inflammation, tissue damage and pain associated with arthritis.

PMID- 27878502
TI  - EMT, cell plasticity and metastasis.
AB  - Carcinoma cells that are induced to suppress their epithelial features and
      upregulate mesenchymal gene expression programs acquire traits that promote an
      invasive and metastatic phenotype. This is achieved through the expression of a
      program termed the epithelial-to-mesenchymal transition (EMT)-a fundamental cell
      biological process that plays key roles in embryogenesis and wound healing. Re
      activation of the EMT during cancer promotes disease progression and enhances the
      metastatic phenotype by bestowing upon previously benign carcinoma cell traits
      such as migration, invasion, resistance to anoikis, chemoresistance and tumour
      initiating potential. Herein, we discuss recent insights into the function of the
      EMT and cancer cell plasticity during cancer progression, with a focus on their
      role in promoting successful completion of the later stages of the metastatic
      cascade.

PMID- 27878501
TI  - Human health impacts of exposure to metals through extreme consumption of fish
      from the Colombian Caribbean Sea.
AB  - The health risks of metal exposure due to the high consumption of fish were
      assessed for a riverine population living on the Caribbean coast of Colombia. The
      concentrations of metals (Cd, Cr, Cu, Hg, Ni, Pb and Zn) in the edible tissues of
      fish were determined and used for risk assessment. The daily fish consumption of
      residents (n = 95) was as high as 283, 366 and 469 g/day in children (CH), women
      of childbearing age (WCHA) and the remaining population groups (RP),
      respectively. The estimation of the potential risk (HQ) indicated that there was
      no health risk from most of the metals, because they did not exceed their related
      reference doses, with values of HQ < 1. Although the concentrations of Pb and Hg
      were not particularly high in fish (<0.2 ug/g), their possible health effects for
      vulnerable groups are of great concern due to the extremely high fish intake. The
      Pb intake for all groups was higher than the lower confidence limit of the
      benchmark dose for nephrotoxicity and neurodevelopmental effects in children. The
      weekly intake of methylmercury was also elevated, with values approximately 3, 2
      and 1.5 times the provisional tolerable weekly intake for CH, WCHA and RP,
      respectively. Moreover, higher Hg levels were found in top predators, whereas
      maximum levels for other metals were found in bottom-feeding fish. This study
      highlights that an accurate data of daily intake, a continuous monitoring of
      metals in fish and their related fish consumption advisories to protect
      subsistence fishing communities are recommended in a local and worldwide context.

PMID- 27878503
TI  - Evaluation of different near-infrared spectroscopy technologies for assessment of
      tissue oxygen saturation during a vascular occlusion test.
AB  - An increasing number of NIRS devices are used to provide measurements of
      peripheral tissue oxygen saturation (StO2). The aim of the present study is to
      test the hypothesis that despite technological differences between devices,
      similar trend values will be obtained during a vascular occlusion test. The
      devices compared are NIRO-200NX, which measures StO2 and oxyhemoglobin by
      spatially resolved spectroscopy and the Beer-Lambert law, respectively, and INVOS
      5100C and Foresight Elite, which both measure StO2 with the Beer-Lambert law,
      enhanced with the spatial resolution technique. Forty consenting adults scheduled
      for CABG surgery were recruited. The respective sensors of the three NIRS devices
      were applied over the brachioradial muscle. Before induction of anesthesia, 3 min
      of ischemia were induced by inflating a blood pressure cuff at the upper arm,
      whereafter cuff pressure was rapidly released. Tissue oxygenation measurements
      included baseline, minimum and maximum values, desaturation and resaturation
      slopes, and rise time. Comparisons between devices were performed with the
      Kruskal-Wallis test with post hoc Mann-Whitney pairwise comparisons. Agreement
      was evaluated using Bland-Altman plots. Oxyhemoglobin measured with NIRO
      responded faster than the other NIRS technologies to changes in peripheral tissue
      oxygenation (20 vs. 27-40 s, p <= 0.01). When comparing INVOS with Foresight,
      oxygenation changes were prompter (upslope 311 [92-523]%/min vs. 114[65
      199]%/min, p <= 0.01) and more pronounced (minimum value 36 [21-48] vs. 45 [40
      51]%, p <= 0.01) with INVOS. Significant differences in tissue oxygen saturation
      measurements were observed, both within the same device as between different
      devices using the same measurement technology.

PMID- 27878504
TI  - Intra- and inter-reader reproducibility of blood flow measurements on the
      ascending aorta and pulmonary artery using cardiac magnetic resonance.
AB  - The aim of our study was to estimate the intra- and inter-reader reproducibility
      of blood flow measurements in the ascending aorta and main pulmonary artery using
      cardiac magnetic resonance (CMR) and a semi-automated segmentation method. The
      ethics committee approved this retrospective study. A total of 50 consecutive
      patients (35 males and 15 females; mean age+/-standard deviation 27+/-13 years)
      affected by congenital heart disease were reviewed. They underwent CMR for flow
      analysis of the ascending aorta and main pulmonary artery (1.5 T, through-plane
      phase-contrast sequences). Two independent readers (R1, trained radiology
      resident; R2, lower-trained technician student) obtained segmented images twice
      (>10-day interval), using a semi-automated method of segmentation. Peak velocity,
      forward and backward flows were obtained. Bland-Altman analysis was used and
      reproducibility was reported as complement to 100% of the ratio between the
      coefficient of repeatability and the mean. R1 intra-reader reproducibility for
      the aorta was 99% (peak velocity), 95% (forward flow) and 49% (backward flow);
      for the pulmonary artery, 99%, 91% and 90%, respectively. R2 intra-reader
      reproducibility was 92%, 91% and 38%; 98%, 86% and 87%, respectively. Inter
      reader reproducibility for the aorta was 91%, 85% and 20%; for the pulmonary
      artery 96%, 75%, and 82%, respectively. Our results showed a good to excellent
      reproducibility of blood flow measurements of CMR together with a semiautomated
      method of segmentation, for all variables except the backward flow of the
      ascending aorta, with a limited impact of operator's training.

PMID- 27878505
TI  - Incidence of seizure in adult patients with intracranial metastatic disease.
AB  - Seizures have considerable impact on a patient's quality of life. While
      guidelines have been articulated to direct clinicians in their management of
      patients with IMD who suffer from seizure, there have been few attempts to
      identify the seizure rate in IMD and to determine which primary cancers may be
      associated with an increased seizure incidence. To determine the incidence of
      seizure in patients with IMD. A systematic review on seizure incidence in
      patients with IMD from the magnetic resonance imaging (MRI) era was performed.
      Articles published between January 2000 and July 2014 with thirty or more
      consecutive adult patients were included in this study. Seizure rate was
      calculated using a pooled data analysis. Differences between observed and
      expected seizure rates between primary tumour sites were examined using the Chi
      square statistic and adjusted standardized residuals. The systematic search
      produced 18 relevant studies, with a total study population of 2012 patients.
      14.6% (n = 294) had seizures. There was a significant association between primary
      tumour site and seizure rates. The seizure rate in patients with primary melanoma
      tumours was significantly greater than expected (z = 2.7; p = .006). The seizure
      rate in patients with primary prostate tumours was significantly lower than
      expected (z = -2.6; p = .008). Patients with intracranial metastasis are at
      significant risk for developing seizure, though at a significantly lower
      incidence than was estimated by studies performed during the CT era. Seizure
      rates appear to be greater in certain primary tumours, such as melanoma.

PMID- 27878506
TI  - The Paradox of Abstraction: Precision Versus Concreteness.
AB  - We introduce a novel measure of abstractness based on the amount of information
      of a concept computed from its position in a semantic taxonomy. We refer to this
      measure as precision. We propose two alternative ways to measure precision, one
      based on the path length from a concept to the root of the taxonomic tree, and
      another one based on the number of direct and indirect descendants. Since more
      information implies greater processing load, we hypothesize that nouns higher in
      precision will have a processing disadvantage in a lexical decision task. We
      contrast precision to concreteness, a common measure of abstractness based on the
      proportion of sensory-based information associated with a concept. Since
      concreteness facilitates cognitive processing, we predict that while both
      concreteness and precision are measures of abstractness, they will have opposite
      effects on performance. In two studies we found empirical support for our
      hypothesis. Precision and concreteness had opposite effects on latency and
      accuracy in a lexical decision task, and these opposite effects were observable
      while controlling for word length, word frequency, affective content and semantic
      diversity. Our results support the view that concepts organization includes
      amodal semantic structures which are independent of sensory information. They
      also suggest that we should distinguish between sensory-based and amount-of
      information-based abstractness.

PMID- 27878507
TI  - The scope and value of an anticoagulation stewardship program at a community
      teaching hospital.
AB  - To report the impact of an inpatient anticoagulation stewardship program at a
      community hospital to promote optimal anticoagulant use. The anticoagulation team
      (ACT) stewardship program consists of two clinical pharmacists and hematologists
      to provide oversight of anticoagulants, high cost reversal agents including
      prothrombin complex concentrate (PCC, KcentraTM), and heparin-induced
      thrombocytopenia (HIT) management. Intervention data and number of charts
      reviewed were collected. Average cost avoidance data was applied to ACT
      interventions to estimate cost savings. The PCC analysis was conducted via
      retrospective chart review during the pre-intervention period. Prospective
      monitoring continued in the post-intervention period to determine the percentage
      of PCC use within the institution's guidelines or approved by ACT or hematology.
      A total of 19,445 patient charts were reviewed, and 1930 (10%) contained
      stewardship opportunity. Of the interventions, 71% were provided to the medical
      service and 22% to surgical services with acceptance rates of 91 and 83%,
      respectively. Intervention cost-avoidance calculated to be $694,217. Regarding
      HIT interventions, 52% of interventions involved pharmacokinetic/pharmacodynamics
      optimization in 18 patients with suspected or confirmed HIT. Regarding PCC use,
      55.8% of PCC orders were considered inappropriate in the pre-invention period
      versus 2.6% post-intervention. Appropriate PCC doses per month post-intervention
      were consistent with pre-intervention doses (7.67 vs. 6.73, respectively). The
      projected annual PCC cost savings is $385,473. The overall estimated financial
      impact of ACT is $799,690 saved. Implementation of an anticoagulation stewardship
      program reduced costs and improved clinical outcomes. It is also expected that
      anticoagulant optimization and provider education improved overall safety.

PMID- 27878508
TI  - Calcium Supplementation Abates the Inhibition Effects of Acetic Acid on
      Saccharomyces cerevisiae.
AB  - The toxic level of acetic acid could be released during the pretreatment of
      lignocellulosic biomass, and an economical method was reported to minimize the
      acidic stress on the fermentation of Saccharomyces cerevisiae by cation
      supplementation. A dose-dependent protection of Ca2+ was monitored, and the
      optimal concentration of Ca2+ was 8 mM under 4.5 g/L acetic acid stress. The
      activities of catalase and superoxide dismutase of yeast cells supplemented with
      optimal Ca2+ increased by 18.6 and 27.3 %, respectively, coupling with an obvious
      decrease of reactive oxygen species content. Cell viability also performed a
      significant increase from 52.4 % (without Ca2+ addition) to 73.56 % (with 8 mM
      Ca2+ addition). No significant improvements were found in the bioethanol yields
      by Ca2+ supplementation; however, the fermentation time was shortened by about 8
      h obviously. Our results illustrated that the Ca2+ supplementation could be an
      economical method to make the bioethanol production more efficient and cost
      effective.

PMID- 27878509
TI  - Purification and Characterization of Hyaluronate Lyase from Arthrobacter
      globiformis A152.
AB  - A hyaluronate lyase was obtained by cultivating Arthrobacter globiformis strain
      A152. The enzyme was purified to homogeneity from the supernatant by ammonium
      sulfate fractionation, Q Sepharose Fast Flow, and Sephadex G-100 chromatography.
      The purification resulted in a 32.78-fold increase in hyaluronate lyase activity
      with specific activity of 297.2 U/mg. The molecular weight of the enzyme
      determined by SDS-PAGE was approximately 73.7 kDa. Using hyaluronic acid (HA) as
      a substrate, the maximal reaction rate (Vmax) and the Michaelis-Menten constant
      (Km) of hyaluronate lyase were found to be 4.76 MUmol/min/ml and 0.11 mg/ml,
      respectively. The optimum pH and temperature values for hyaluronate lyase
      activity were pH 6.0 and 42  degrees C, respectively. This enzyme was stable at
      pH 4-10, 5-7, and 5-7 at 4, 37, and 42  degrees C, respectively. Investigation
      about temperature effects on hyaluronate lyase displayed that it was stable at 30
      37  degrees C and also showed high activity at 37  degrees C. The enzymatic
      activity was enhanced by Ca2+ and was strongly inhibited by Cu2+ and SDS. These
      properties suggested that the hyaluronate lyase in this study could bring
      promising prospects in medical and industry applications.

PMID- 27878510
TI  - Influence of perioperative complication severity on 1- and 2-year outcomes of low
      back surgery.
AB  - BACKGROUND: Several factors potentially influence outcomes of surgery, including
      perioperative complications. Complications may take many forms and the Clavien
      Dindo (CD) classification is designed to categorize them by degree of severity.
      The aim of this study was to evaluate the influence of perioperative
      complications by severity categorization on the 1-and 2-year pain and disability
      outcomes for patients who received low back surgery. MATERIALS AND METHODS: Data
      used for the study involved a purposive sample (N = 477; 8.1%) from a spine
      outcomes registry of 5876 patients who received spine surgery and encountered
      complications. All complications were categorized using the CD classification and
      were collapsed according to distribution frequencies, i.e., Grade I-II and Grade
      III-V. Adjusted and unadjusted regression analyses were used to determine the
      association between CD classification and 1- and 2-year outcomes. RESULTS: The
      majority of surgical complications were Grade III-V (N = 358; 75.1%), with two
      incidences in which death occurred. For the unadjusted models, there were no
      significant associations between CD classification categorizations for 1-year
      outcomes; however, 2-year outcomes were significantly worse (P <0.05) for those
      with Grade III-V categorization. When adjusted and controlled for baseline
      characteristics, CD classification did not influence 1-or 2-year pain and
      disability outcomes. CONCLUSIONS: When control variables are considered, the
      severity of perioperative surgical complications does not appear to influence 1-
      or 2-year pain and disability outcomes. LEVEL OF EVIDENCE: Level 4.

PMID- 27878512
TI  - Nickel Oxide Nanoparticles Induce Oxidative DNA Damage and Apoptosis in Kidney
      Cell Line (NRK-52E).
AB  - Increasing use of nickel oxide (NiO) nanoparticles in different applications
      results in high occupational and environmental exposure to them. However, the
      effect of NiO nanoparticles on human health is still poorly documented. It was
      aimed to investigate the toxic potentials of NiO nanoparticles on NRK-52E kidney
      epithelial cells. The following assays were used: the nanoparticle
      characterization by transmission electron microscopy (TEM) and dynamic light
      scattering (DLS); the determination of cellular uptake and morphologic changes by
      TEM and inductively coupled plasma-mass spectrometry (ICP-MS); MTT and neutral
      red uptake (NRU) assays for cytotoxicity; comet assay for genotoxicity; the
      determination of malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), protein
      carbonyl (PC) and glutathione (GSH) levels by enzyme-linked immune sorbent assays
      (ELISA) for the potential of oxidative damage; and Annexin V-FITC apoptosis
      detection assay with propidium iodide (PI) for apoptosis. The nanoparticles were
      taken up by the cells and induced dose-dependent DNA damage by comet assay and
      oxidative damage evidenced by increasing levels of MDA, 8-OHdG, PC and depletion
      of GSH. At >=294.0 MUg/mL concentration, NiO nanoparticles caused 50% inhibition
      in cell viability by the cytotoxicity assays. Also, they showed
      apoptotic/necrotic effects on the cells as well as some morphological changes. We
      have indicated that their cellular damage effects should raise concern about the
      safety associated with their applications in consumer products.

PMID- 27878511
TI  - New Challenges in the Treatment of Patients With Left Ventricular Support: LVAD
      Thrombosis.
AB  - Mechanical circulatory support has revolutionized the treatment of heart failure,
      affording patients significantly improved survival and quality of life. However,
      further advancements in this technology have been hindered by adverse events,
      particularly gastrointestinal bleeding, driveline infection, stroke, and device
      thrombosis. Recently, there has been a renewed focus on device thrombosis as the
      reported incidence has increased. This review focuses on an update on the
      diagnostic modalities and current treatment algorithms of this serious
      complication.

PMID- 27878513
TI  - Nanoselenium Supplementation of Heat-Stressed Broilers: Effects on Performance,
      Carcass Characteristics, Blood Metabolites, Immune Response, Antioxidant Status,
      and Jejunal Morphology.
AB  - An experiment was conducted to investigate the effects of dietary nanoselenium
      supplementation at 0, 0.6 and 1.2 mg/kg of diet on growth performance, serum
      biochemical parameters, immune response, antioxidant capacity, and jejunal
      morphology of 29-d-old male broilers subjected to heat stress at 37 +/- 1 degrees
      C for 14 d. Broilers were fed for 42 d on the experimental diets. The results
      showed that nanoselenium supplementation had no effect on growth performance, but
      it supplementation at the rate of 1.2 mg/kg diet decreased the serum
      concentration of cholesterol prior to the heat exposure. Further, dietary
      nanoselenium supplementation linearly increased the high-density lipoprotein
      cholesterol concentration, while linearly decreased those of low-density
      lipoprotein cholesterol and aspartate aminotransferase in the serum before
      applying heat stress. Compared with thermoneutral temperature, heat stress
      reduced body mass gain, feed intake, percentages of carcass, breast, leg,
      abdominal fat, bursa of Fabricius, thymus, antibody response against sheep red
      blood cells, serum concentration of protein, erythrocyte activities of
      glutathione peroxidase and superoxide dismutase, jejunal villus height, and
      villus height to crypt depth ratio, while increased feed conversion ratio,
      percentages of liver, gizzard, pancreas, gallbladder, heart, and the
      concentrations of aspartate aminotransferase and malondialdehyde. Dietary
      supplementation of nanoselenium linearly reduced the abdominal fat and liver
      percentages, while linearly increased the activity of glutathione peroxidase and
      villus height in heat-stressed broilers. Furthermore, the lower level of
      nanoselenium decreased the percentages of gizzard and heart in broilers under
      heat stress. The diet supplemented with 1.2 mg/kg nanoselenium improved feed
      conversion ratio and increased antibody response against sheep red blood cells,
      activity of superoxide dismutase, and villus height to crypt depth ratio, but
      decreased the serum concentrations of cholesterol, low-density lipoprotein
      cholesterol, and malondialdehyde in heat-stressed broilers. The results suggest
      that supplemental nanoselenium improved growth performance, internal organs
      health, immune response, and jejunal morphology by alleviating the oxidative
      stress induced by heat stress.

PMID- 27878514
TI  - Emergence of hydrogen bonds from molecular dynamics simulation of substituted N
      phenylthiourea-catechol oxidase complex.
AB  - A series of N-phenylthiourea derivatives was built starting from the X-ray
      structure in the molecular mechanics framework and the interaction profile in the
      complex with the catechol oxidase was traced using molecular dynamics simulation.
      The results showed that the geometry and interactions between ligand and receptor
      were highly related to the position of the substituted side chains of phenyl
      moiety. At the end of molecular dynamics run, a concentrated multicenter hydrogen
      bond was created between the substituted ligand and receptor. The conformation of
      the ligand itself were also restricted in the receptor pocket. Furthermore, the
      simulation time of 50 ns were found to be long enough to explore the relevant
      conformational space and the stationary behavior of the molecular dynamic could
      be observed.

PMID- 27878515
TI  - Could 82Rb-PET be the next best thing in evaluation of myocardial salvage?

PMID- 27878519
TI  - Polymicrobial pulmonary infections in cancer patients with underlying solid
      tumors.

PMID- 27878517
TI  - Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant.
AB  - Major depression is a serious psychiatric disorder and remains a leading cause of
      disability worldwide. Conventional antidepressants take at least several weeks to
      achieve a therapeutic response and this lag period has hindered their ability to
      attain beneficial effects in depressed individuals at high risk of suicide. The
      non-competitive N-methyl-D-aspartate glutamate receptor antagonist ketamine has
      been shown to have rapid antidepressant effects in both rodents and humans. The
      emergence of ketamine as a fast-acting antidepressant provides promising new
      insights into the development of a rapid treatment response in patients with
      clinical depression. However, its safety and toxicity remain a concern. In this
      review, we focus on the limitations of ketamine, including neurotoxicity,
      cognitive dysfunction, adverse events associated with mental status,
      psychotomimetic effects, cardiovascular events, and uropathic effects. Studies
      have shown that its safety and tolerability profiles are generally good at low
      doses and with short-term treatment in depressed patients. The adverse events
      associated with ketamine usually occur with very high doses that are administered
      for prolonged periods of time and can be relieved by cessation. The
      antidepressant actions of its two enantiomers, S-ketamine (esketamine) and R
      ketamine, are also discussed. R-ketamine has greater antidepressant actions than
      S-ketamine, without ketamine-related side-effects. Future treatment strategies
      should consider using R-ketamine for the treatment of depressed patients to
      decrease the risk of adverse events associated with long-term ketamine use.

PMID- 27878516
TI  - Axonal Excitability in Amyotrophic Lateral Sclerosis : Axonal Excitability in
      ALS.
AB  - Axonal excitability testing provides in vivo assessment of axonal ion channel
      function and membrane potential. Excitability techniques have provided insights
      into the pathophysiological mechanisms underlying the development of
      neurodegeneration and clinical features of amyotrophic lateral sclerosis (ALS)
      and related neuromuscular disorders. Specifically, abnormalities of Na+ and K+
      conductances contribute to development of membrane hyperexcitability in ALS,
      thereby leading to symptom generation of muscle cramps and fasciculations, in
      addition to promoting a neurodegenerative cascade via Ca2+-mediated processes.
      Modulation of axonal ion channel function in ALS has resulted in significant
      symptomatic improvement that has been accompanied by stabilization of axonal
      excitability parameters. Separately, axonal ion channel dysfunction evolves with
      disease progression and correlates with survival, thereby serving as a potential
      therapeutic biomarker in ALS. The present review provides an overview of axonal
      excitability techniques and the physiological mechanisms underlying membrane
      excitability, with a focus on the role of axonal ion channel dysfunction in motor
      neuron disease and related neuromuscular diseases.

PMID- 27878520
TI  - A Coumarin-Based Luminescent Chemosensor for Recognition of Cu2+ and its In-Situ
      Complex for CN- Sensing via Cu2+ Displacement Approach.
AB  - A new coumarin based chemosensor has been developed for selective fluorescent
      recognition of Cu2+ in MeOH/H2O (4:1, v/v at pH = 7.2 aqueous solution) medium
      with 1:1 binding stoichiometry. The in-situ prepared Cu2+ complex displays high
      selectivity towards CN- via Cu2+ displacement approach with detection limit in
      the micro molar range. Moreover, in presence of Cu2+, the receptor exhibits
      reversible emission change with EDTA and thus offers an interesting property of
      molecular 'IMPLICATION' logic gate with Cu2+ and EDTA as chemical inputs.

PMID- 27878518
TI  - Comparative efficacy of alpha-linolenic acid and gamma-linolenic acid to
      attenuate valproic acid-induced autism-like features.
AB  - The present study was undertaken to elucidate the effect of alpha-linolenic acid
      (ALA, 18:3, omega-3) and gamma-linolenic acid (GLA, 18:3, omega-6) on
      experimental autism features induced by early prenatal exposure to valproic acid
      (VPA) in albino wistar pups. The pups were scrutinized on the accounts of
      behavioral, biochemical, and inflammatory markers, and the results suggested that
      the GLA can impart significant protection in comparison to ALA against VPA
      induced autism features. When scrutinized histopathologically, the cerebellum of
      the GLA-treated animals was evident for more marked protection toward neuronal
      degeneration and neuronal loss in comparison to ALA. Concomitant administration
      of ALA and GLA with VPA demonstrated a marked cutdown in the Pgp 9.5 expression
      with GLA having more pronounced effect. Henceforth, it can be concluded that ALA
      and GLA can impart favorable protection against the VPA-induced autism-like
      features with GLA having pronounced effect.

PMID- 27878521
TI  - Dual-Labeled Time-Resolved Immunofluorometric Assay for the Simultaneous
      Quantitative Detection of Hepatitis B Virus Antigens in Human Serum.
AB  - In this paper, a novel time-resolved fluorescence immunoassay (TRFIA) is
      described that allows the simultaneous quantitative detection of hepatitis B
      virus surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in human serum to
      aid the diagnosis and monitoring of hepatitis B virus infection. The proposed
      method was developed based on a two-step sandwich immunoassay protocol in which
      monoclonal antibodies against HBsAg and HBeAg were co-coated in 96 microtitration
      wells, then tracer polyclonal antibodies against HBsAg labeled with samarium and
      tracer monoclonal antibodies against HBeAg labeled with europium chelates were
      used for detection. The detection range was 0.1-150 IU/mL for HBsAg and 0.5-160
      PEIU/mL for HBeAg, and the detection limits were 0.03 IU/L and 0.09 PEIU/ml,
      respectively. The intra- and inter-assay coefficients of variation were below 8 %
      for both virus antigens. The dilution linearity and accuracy of the assay were
      satisfactory. No statistically significant differences were observed in
      sensitivity or specificity for the serum samples between the dual-label TRFIA and
      a commercial single-label TRFIA. These results demonstrate that an effective,
      reliable and convenient HBsAg/HBeAg dual-label TRFIA was successfully developed
      that may be clinically applicable for blood screening to monitor the course of
      hepatitis B virus infection and predict treatment responses.

PMID- 27878522
TI  - Informal Care Time and Cost in a Large Clinical Trial Sample of Patients with
      Mild to Moderate Alzheimer's Disease: Determinants and Level of Change Observed.
AB  - INTRODUCTION: We evaluate the association between caregiver (informal) time/cost
      and illness severity from two recently completed clinical trials of an
      investigational drug for Alzheimer's disease (AD). METHODS: Changes from baseline
      caregiver time were calculated and treatment effects analyzed using a restricted
      maximum likelihood-based mixed model for repeated measures. Four separate models
      were then estimated to examine the association between caregiver time costs and
      the clinical endpoints measured during the trials, including cognition (MMSE),
      function (DAD), behavior (NPI), global disability (CDR) and dependence (DS).
      RESULTS: Caregiver time cost was significantly associated with all clinical
      measures of illness severity with a 1-unit change in MMSE, DAD, NPI, CDR and DS
      associated with a 11.57%, 4.81-4.97%, 3.58-3.67%, 42.52% and 71.05% change,
      respectively, in primary caregiver time cost. The association between caregiver
      time cost and DS was the strongest of all the associations examined. CONCLUSION:
      Caregiver time costs increase with increasing AD severity in all key domains of
      AD (cognition, function, behavior, global disability and dependence on others).
      Our analysis demonstrated that patient dependence is a particularly important
      predictor of caregiver time costs and should be considered as a potential outcome
      measure in intervention clinical trials in AD. FUNDING: Pfizer Inc. and Janssen
      Alzheimer Immunotherapy Research and Development.

PMID- 27878523
TI  - Intravenous ketamine for subacute treatment of refractory chronic migraine: a
      case series.
AB  - BACKGROUND: Refractory migraine is a challenging condition with great impact on
      health related quality of life. Intravenous (IV) ketamine has been previously
      used to treat various refractory pain conditions. We present a series of patients
      with refractory migraine treated with intravenous ketamine in the hospital
      setting. METHODS: Based on retrospective chart review, we identified six patients
      with refractory migraine admitted from 2010 through 2014 for treatment with
      intravenous ketamine. Ketamine was administered using a standard protocol
      starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h
      as tolerated until the target pain score of 3/10 was achieved and maintained for
      at least 8 h. Visual Analogue Scale (VAS) scores at time of hospital admission
      were obtained as well as average baseline VAS scores prior to ketamine infusion.
      A phone interview was conducted for follow-up of migraine response in the 3 to 6
      months following ketamine infusion. RESULTS: The study sample had a median age of
      36.5 years (range 29-54) and 83% were women. Pre-treatment pain scores ranged
      from 9 to 10. All patients achieved a target pain level of 3 or less for 8 h; the
      average ketamine infusion rate at target was 0.34 mg/kg/hour (range 0.12-0.42
      mg/kg/hr). One patient reported a transient out-of-body hallucination following
      an increase in the infusion rate, which resolved after decreasing the rate. There
      were no other significant side effects. CONCLUSION: IV ketamine was safely
      administered in the hospital setting to patients with refractory chronic
      migraine. Treatment was associated with short term improvement in pain severity
      in 6 of 6 patients with refractory chronic migraine. Prospective placebo
      controlled trials are needed to assess short term and long-term efficacy of IV
      ketamine in refractory chronic migraine.

PMID- 27878524
TI  - Muscle Injuries in Sports: A New Evidence-Informed and Expert Consensus-Based
      Classification with Clinical Application.
AB  - Muscle injuries are among the most common injuries in sport and continue to be a
      major concern because of training and competition time loss, challenging decision
      making regarding treatment and return to sport, and a relatively high recurrence
      rate. An adequate classification of muscle injury is essential for a full
      understanding of the injury and to optimize its management and return-to-play
      process. The ongoing failure to establish a classification system with broad
      acceptance has resulted from factors such as limited clinical applicability, and
      the inclusion of subjective findings and ambiguous terminology. The purpose of
      this article was to describe a classification system for muscle injuries with
      easy clinical application, adequate grouping of injuries with similar functional
      impairment, and potential prognostic value. This evidence-informed and expert
      consensus-based classification system for muscle injuries is based on a four
      letter initialism system: MLG-R, respectively referring to the mechanism of
      injury (M), location of injury (L), grading of severity (G), and number of muscle
      re-injuries (R). The goal of the classification is to enhance communication
      between healthcare and sports-related professionals and facilitate rehabilitation
      and return-to-play decision making.

PMID- 27878525
TI  - Genetics of Frontotemporal Dementia.
AB  - Frontotemporal dementia (FTD) is the second most common cause of dementia
      following Alzheimer's disease (AD). Between 20 and 50% of cases are familial.
      Mutations in MAPT, GRN and C9orf72 are found in 60% of familial FTD cases.
      C9orf72 mutations are the most common and account for 25%. Rarer mutations (<5%)
      occur in other genes such as VPC, CHMP2B, TARDP, FUS, ITM2B, TBK1 and TBP. The
      diagnosis is often challenging due to symptom overlap with AD and other
      conditions. We review the genetics, clinical presentations, neuroimaging,
      neuropathology, animal studies and therapeutic trials in FTD. We describe
      clinical scenarios including the original family with the tau stem loop mutation
      (+14) and also the recently discovered 'missing tau' mutation +15 that 'closed
      the loop' in 2015.

PMID- 27878528
TI  - Development of a Dot-Blot Assay for the Detection of Mould-Specific IgE in the
      Belgian Population.
AB  - BACKGROUND: Data on mould sensitization in the general population are scarce and
      mostly on Aspergillus fumigatus, Alternaria alternata and Cladosporium herbarum.
      OBJECTIVES: To validate a dot-blot assay for the detection of specific IgE and
      evaluate the prevalence of mould sensitization in a healthy population. METHODS:
      The dot-blot assay was validated against the CAP test. Sensitization rate to ten
      common indoor and outdoor mould species in 344 serum samples was calculated. For
      each serum with more than one reactivity, the "major sensitization" defined as
      the strongest response against a single mould species was calculated. RESULTS:
      Intra- and inter-assay variations were both below 20%, and the positivity
      threshold of the test was of 0.418 kU/L for A. fumigatus. Correlation with CAP
      results was strong. The overall prevalence of sensitization was 32.8%, and the
      commonest sensitizations were against A. alternaria, A. flavus and A. niger
      (around 15%). The most frequent "major reactivities" were against A. niger and A.
      alternata (20-30%). In 25.1% of the samples, "major reactivities" were directed
      against a group of moulds commonly found indoor (Penicillium spp., Aspergillus
      versicolor, Cladosporium sphaerospermum and Cladosporium cladosporioides).
      CONCLUSIONS: The dot-blot assay was validated for the detection of mould-specific
      IgE. In the general population, sensitization to indoor species was common and
      accounted for 25% of overall mould sensitizations.

PMID- 27878526
TI  - Intravenous Vancomycin Dosing in the Elderly: A Focus on Clinical Issues and
      Practical Application.
AB  - The elderly population can be divided into three distinct age groups: 65-74 years
      (young-old), 75-84 years (middle-old), and 85+ years (old-old). Despite evidence
      of a shift in leading causes for mortality in the elderly from infectious
      diseases to chronic conditions, infections are still a serious cause of death in
      this population. These patients are at increased risk due to weakened immune
      systems, an increased prevalence of underlying comorbidities, and decreased
      physiologic reserves to fight infection. Additionally, elderly patients,
      especially adults in institutional settings, are at an increased risk of
      colonization and subsequent infection with methicillin-resistant Staphylococcus
      aureus at a rate that is five times higher than in younger individuals, causing
      an increase in empiric and definitive vancomycin use. Elderly patients have
      unique characteristics that make dosing vancomycin a challenge for clinicians,
      such as increased volume of distribution and decreased renal function. Using the
      best available evidence, it is recommended to initiate lower empiric maintenance
      doses and monitor vancomycin serum concentrations earlier than steady state to
      accurately calculate drug elimination and make appropriate dose adjustments.

PMID- 27878531
TI  - Beyond dichotomies: Gender and intersecting inequalities in climate change
      studies.
AB  - Climate change and related adaptation strategies have gender-differentiated
      impacts. This paper reviews how gender is framed in 41 papers on climate change
      adaptation through an intersectionality lens. The main findings show that while
      intersectional analysis has demonstrated many advantages for a comprehensive
      study of gender, it has not yet entered the field of climate change and gender.
      In climate change studies, gender is mostly handled in a men-versus-women
      dichotomy and little or no attention has been paid to power and social and
      political relations. These gaps which are echoed in other domains of development
      and gender research depict a 'feminization of vulnerability' and reinforce a
      'victimization' discourse within climate change studies. We argue that a critical
      intersectional assessment would contribute to unveil agency and emancipatory
      pathways in the adaptation process by providing a better understanding of how the
      differential impacts of climate change shape, and are shaped by, the complex
      power dynamics of existing social and political relations.

PMID- 27878529
TI  - Association between copy-number variation on metabolic phenotypes and HDL-C
      levels in patients with polycystic ovary syndrome.
AB  - Polygenic diseases with a broad phenotypic spectrum, such as polycystic ovary
      syndrome (PCOS), present a particular challenge in terms of identifying the
      underlying genetic mechanisms, nevertheless genetic variants have impact on the
      individual phenotype. We aimed to determine if next to genetic variations like
      SNPs further mechanisms might play a role in the pathogenesis of PCOS. We
      examined the effect of copy-number variations (CNVs) on metabolic phenotypes in
      PCOS. The intragenic rs1244979, rs2815752 in NEGR1 gene, and rs780094 in GCKR
      gene were genotyped and CNVs were determined by droplet digital polymerase chain
      reaction (ddPCR) in PCOS patients (n = 153) and controls without metabolic
      syndrome (n = 142). The study indicated that SNPs are not associated with the
      pathogenesis of PCOS but affect metabolic phenotypes. The CNVs investigated show
      a lower variability in PCOS than in CON. Furthermore, we provided direct evidence
      that the copy number, but not the genotype of the CNV in the genomic regions of
      rs780094(GCKR) is associated with low level of high-density lipoprotein
      cholesterol in PCOS. This study supports the hypothesis that not only genetic
      variants, but also CNVs in metabolically relevant genes, have an effect on
      metabolic phenotypes in our group of PCOS patients.

PMID- 27878530
TI  - Gendered medicinal plant knowledge contributions to adaptive capacity and health
      sovereignty in Amazonia.
AB  - Local medical systems are key elements of social-ecological systems as they
      provide culturally appropriate and locally accessible health care options,
      especially for populations with scarce access to biomedicine. The adaptive
      capacity of local medical systems generally rests on two pillars: species
      diversity and a robust local knowledge system, both threatened by local and
      global environmental change. We first present a conceptual framework to guide the
      assessment of knowledge diversity and redundancy in local medicinal knowledge
      systems through a gender lens. Then, we apply this conceptual framework to our
      research on the local medicinal plant knowledge of the Tsimane' Amerindians. Our
      results suggest that Tsimane' medicinal plant knowledge is gendered and that the
      frequency of reported ailments and the redundancy of knowledge used to treat them
      are positively associated. We discuss the implications of knowledge diversity and
      redundancy for local knowledge systems' adaptive capacity, resilience, and health
      sovereignty.

PMID- 27878532
TI  - The diversity of gendered adaptation strategies to climate change of Indian
      farmers: A feminist intersectional approach.
AB  - This paper examines climate change adaptation and gender issues through an
      application of a feminist intersectional approach. This approach permits the
      identification of diverse adaptation responses arising from the existence of
      multiple and fragmented dimensions of identity (including gender) that intersect
      with power relations to shape situation-specific interactions between farmers and
      ecosystems. Based on results from contrasting research cases in Bihar and
      Uttarakhand, India, this paper demonstrates, inter alia, that there are
      geographically determined gendered preferences and adoption strategies regarding
      adaptation options and that these are influenced by the socio-ecological context
      and institutional dynamics. Intersecting identities, such as caste, wealth, age
      and gender, influence decisions and reveal power dynamics and negotiation within
      the household and the community, as well as barriers to adaptation among groups.
      Overall, the findings suggest that a feminist intersectional approach does appear
      to be useful and worth further exploration in the context of climate change
      adaptation. In particular, future research could benefit from more emphasis on a
      nuanced analysis of the intra-gender differences that shape adaptive capacity to
      climate change.

PMID- 27878533
TI  - Gender perspectives in resilience, vulnerability and adaptation to global
      environmental change.
AB  - The main goal of this special issue is to offer a room for interdisciplinary and
      engaged research in global environmental change (GEC), where gender plays a key
      role in building resilience and adaptation pathways. In this editorial paper, we
      explain the background setting, key questions and core approaches of gender and
      feminist research in vulnerability, resilience and adaptation to GEC.
      Highlighting the interlinkages between gender and GEC, we introduce the main
      contributions of the collection of 11 papers in this special issue. Nine
      empirical papers from around the globe allow to understand how gendered diversity
      in knowledge, institutions and everyday practices matters in producing barriers
      and options for achieving resilience and adaptive capacity in societies.
      Additionally, two papers contribute to the theoretical debate through a
      systematic review and an insight on the relevance of intersectional framings
      within GEC research and development programming.

PMID- 27878534
TI  - Gender-specific responses to climate variability in a semi-arid ecosystem in
      northern Benin.
AB  - Highly erratic rainfall patterns in northern Benin complicate the ability of
      rural farmers to engage in subsistence agriculture. This research explores gender
      specific responses to climate variability in the context of agrarian Benin
      through a household survey (n = 260) and an experimental gaming exercise among a
      subset of the survey respondents. Although men and women from the sample
      population are equally aware of climate variability and share similar coping
      strategies, their specific land-use strategies, preferences, and motivations are
      distinct. Over the long term, these differences would likely lead to dissimilar
      coping strategies and vulnerability to the effects of climate change. Examination
      of gender-specific land-use responses to climate change and anticipatory learning
      can enhance efforts to improve adaptability and resilience among rural
      subsistence farmers.

PMID- 27878535
TI  - Understanding adaptive capacity and capacity to innovate in social-ecological
      systems: Applying a gender lens.
AB  - Development policy increasingly focuses on building capacities to respond to
      change (adaptation), and to drive change (innovation). Few studies, however,
      focus specifically on the social and gender differentiation of capacities to
      adapt and innovate. We address this gap using a qualitative study in three
      communities in Solomon Islands; a developing country, where rural livelihoods and
      well-being are tightly tied to agriculture and fisheries. We find the five
      dimensions of capacity to adapt and to innovate (i.e. assets, flexibility,
      learning, social organisation, agency) to be mutually dependant. For example,
      limits to education, physical mobility and agency meant that women and youth,
      particularly, felt it was difficult to establish relations with external agencies
      to access technical support or new information important for innovating or
      adapting. Willingness to bear risk and to challenge social norms hindered both
      women's and men's capacity to innovate, albeit to differing degrees. Our findings
      are of value to those aspiring for equitable improvements to well-being within
      dynamic and diverse social-ecological systems.

PMID- 27878536
TI  - Gendered vulnerabilities and grassroots adaptation initiatives in home gardens
      and small orchards in Northwest Mexico.
AB  - With the retreat of the state under neoliberalism, the lack of (or negligible)
      government and non-governmental support reasserts grassroots initiatives as a
      global-change strategy. A feminist political ecology approach and the concept of
      adverse inclusion were used to facilitate an analysis of social differences
      shaping local-level adaptive responses. Adaptive responses of small farmers in
      the border village of San Ignacio, Sonora, Mexico, who are increasingly
      vulnerable to climate change, water scarcity, and changing labor markets were
      studied. Gender differences in production sites translate into diverse
      vulnerabilities and adaptive strategies. Local capacities and initiatives should
      be a focus of research and policy to avoid viewing women and men as passive in
      the face of global change. The dynamic strategies of San Ignacio women and men in
      home gardens and small orchards hold lessons for other regions particularly
      related to adaptation to climate change via agrobiodiversity, water resource
      management, and diversified agricultural livelihoods.

PMID- 27878537
TI  - A synthesis of convergent reflections, tensions and silences in linking gender
      and global environmental change research.
AB  - This synthesis article joins the authors of the special issue "Gender
      perspectives in resilience, vulnerability and adaptation to global environmental
      change" in a common reflective dialogue about the main contributions of their
      papers. In sum, here we reflect on links between gender and feminist approaches
      to research in adaptation and resilience in global environmental change (GEC).
      The main theoretical contributions of this special issue are threefold:
      emphasizing the relevance of power relations in feminist political ecology,
      bringing the livelihood and intersectionality approaches into GEC, and linking
      resilience theories and critical feminist research. Empirical insights on key
      debates in GEC studies are also highlighted from the nine cases analysed, from
      Europe, the Americas, Asia, Africa and the Pacific. Further, the special issue
      also contributes to broaden the gender approach in adaptation to GEC by
      incorporating research sites in the Global North alongside sites from the Global
      South. This paper examines and compares the main approaches adopted (e.g.
      qualitative or mixed methods) and the methodological challenges that derive from
      intersectional perspectives. Finally, key messages for policy agendas and further
      research are drawn from the common reflection.

PMID- 27878538
TI  - Enhancing and expanding intersectional research for climate change adaptation in
      agrarian settings.
AB  - Most current approaches focused on vulnerability, resilience, and adaptation to
      climate change frame gender and its influence in a manner out-of-step with
      contemporary academic and international development research. The tendency to
      rely on analyses of the sex-disaggregated gender categories of 'men' and 'women'
      as sole or principal divisions explaining the abilities of different people
      within a group to adapt to climate change, illustrates this problem. This framing
      of gender persists in spite of established bodies of knowledge that show how
      roles and responsibilities that influence a person's ability to deal with climate
      induced and other stressors emerge at the intersection of diverse identity
      categories, including but not limited to gender, age, seniority, ethnicity,
      marital status, and livelihoods. Here, we provide a review of relevant literature
      on this topic and argue that approaching vulnerability to climate change through
      intersectional understandings of identity can help improve adaptation
      programming, project design, implementation, and outcomes.

PMID- 27878539
TI  - What's counted as a reindeer herder? Gender and the adaptive capacity of Sami
      reindeer herding communities in Sweden.
AB  - Researchers of adaptive capacity and sustainable livelihoods have frequently used
      social, cultural, human, economic and institutional capitals to better understand
      how rural and resource-dependent communities address environmental, social and
      economic stresses. Yet few studies have considered how men and women contribute
      differently to these capitals to support community resilience overall. Our
      research sought to understand the differential contributions of Sami men and
      women to the adaptive capacity of reindeer husbandry and reindeer herding
      communities in northern Sweden. Our focus revealed a gendered division of labour
      in reindeer herding as an economic enterprise as well as gendered contributions
      to a broader conceptualization of reindeer husbandry as a family and community
      based practice, and as a livelihood and cultural tradition. Based on our results,
      we recommend that community resilience be enhanced by generating more
      opportunities for men to achieve higher levels of human and economic capital
      (particularly outside of herding activities) and encouraging women to contribute
      more directly to institutional capital by participating in the formation and
      implementation of legislation, policies and plans.

PMID- 27878540
TI  - Some years you live like a coyote: Gendered practices of cultural resilience in
      working rangeland landscapes.
AB  - Rangeland researchers are increasingly interested in understanding working
      rangelands as integrated social-ecological systems and in investigating the
      contexts of human decision-making processes that support system resilience. U.S.
      public lands ranchers are key partners in rangeland conservation, but the role of
      women in building system resilience has not yet been explored. We conducted life
      history interviews with 19 ranching women in the Southwestern United States. We
      analyzed the resulting transcripts by identifying contradictions between women's
      material practices and traditional discourses in the ranching livelihood that
      illustrated women's efforts to maintain both a way of life and a living during
      social and ecological change. These gendered practices of cultural resilience
      included self-sacrifice during difficult financial times, engagement with non
      rancher networks, and efforts to transfer cultural and technical knowledge. We
      argue that the key part ranchers play in rangeland conservation cannot be fully
      understood without a consideration of gendered practices of cultural resilience.

PMID- 27878541
TI  - Gendered knowledge and adaptive practices: Differentiation and change in Mwanga
      District, Tanzania.
AB  - We examine the wider social knowledge domain that complements technical and
      environmental knowledge in enabling adaptive practices through two case studies
      in Tanzania. We are concerned with knowledge production that is shaped by
      gendered exclusion from the main thrusts of planned adaptation, in the practice
      of irrigation in a dryland village and the adoption of fast-maturing seed
      varieties in a highland village. The findings draw on data from a household
      survey, community workshops, and key informant interviews. The largest challenge
      to effective adaptation is a lack of access to the social networks and
      institutions that allocate resources needed for adaptation. Results demonstrate
      the social differentiation of local knowledge, and how it is entwined with
      adaptive practices that emerge in relation to gendered mechanisms of access. We
      conclude that community-based adaptation can learn from engaging the broader
      social knowledge base in evaluating priorities for coping with greater climate
      variability.

PMID- 27878542
TI  - The impact of gender-blindness on social-ecological resilience: The case of a
      communal pasture in the highlands of Ethiopia.
AB  - We studied how the failure to take into account gendered roles in the management
      of a communal pasture can affect the resilience of this social-ecological system.
      Data were collected using qualitative methods, including focus group discussions,
      in-depth interviews, and participant observations from one community in the
      highlands of Ethiopia. The results show that women are excluded from the informal
      institution that defines the access and use rules which guide the management of
      the communal pasture. Consequently, women's knowledge, preferences, and needs are
      not taken into account. This negatively affects the resilience of the communal
      pasture in two ways. Firstly, the exclusion of women's knowledge leads to future
      adaptation options being overlooked. Secondly, as a result of the failure to
      address women's needs, they start to question the legitimacy of the informal
      institution. The case study thus shows how excluding women, i.e., side-lining
      their knowledge and needs, weakens social learning and the adaptiveness of the
      management rules. Being blind to gender-related issues may thus undermine the
      resilience of a social-ecological system.

PMID- 27878544
TI  - Spatial and temporal assessment of surface water quality in the Arka River,
      Akkar, Lebanon.
AB  - Surface water quality monitoring constitutes a crucial and important step in any
      water quality management system. Twenty-three physicochemical and microbiological
      parameters were assessed in surface water samples collected from the Arka River
      located in the Akkar District, north of Lebanon. Eight sampling locations were
      considered along the river and seven sampling campaigns were performed in order
      to evaluate spatial and temporal influences. The extraction of relevant
      information from this relatively large data set was done using principal
      component analysis (PCA), being a very well established chemometric tool in this
      field. In a first step, extracted PCA loadings revealed the implication of
      several physicochemical parameters in the discriminations and trends highlighted
      by PCA scores, mainly due to soil leaching and seawater intrusion. However,
      further investigations showed the implication of organic and bacterial parameters
      in the discrimination of stations in the Akkar flatland. These discriminations
      probably refer to anthropogenic pollution coming from the agricultural area and
      the surrounding villages. Specific ultraviolet absorption (SUVA) indices
      confirmed these findings since values decreased for samples collected across the
      villages and the flatland, indicating an increase in anthropogenic dissolved
      organic matter. This study will hopefully help the national and local authorities
      to ameliorate the surface water quality management, enabling its proper use for
      irrigation purposes.

PMID- 27878543
TI  - A new predictive model for continuous positive airway pressure in the treatment
      of obstructive sleep apnea.
AB  - BACKGROUND: Numerous mathematical formulas have been developed to determine
      continuous positive airway pressure (CPAP) without an in-laboratory titration
      study. Recent studies have shown that style of CPAP mask can affect the optimal
      pressure requirement. However, none of the current models take mask style into
      account. Therefore, the goal of this study was to develop new predictive models
      of CPAP that take into account the style of mask interface. METHODS: Data from
      200 subjects with attended CPAP titrations during overnight polysomnograms using
      nasal masks and 132 subjects using oronasal masks were randomized and split into
      either a model development or validation group. Predictive models were then
      created in each model development group and the accuracy of the models was then
      tested in the model validation groups. RESULTS: The correlation between our new
      oronasal model and laboratory determined optimal CPAP was significant, r = 0.61,
      p < 0.001. Our nasal formula was also significantly related to laboratory
      determined optimal CPAP, r = 0.35, p < 0.001. The oronasal model created in our
      study significantly outperformed the original CPAP predictive model developed by
      Miljeteig and Hoffstein, z = 1.99, p < 0.05. The predictive performance of our
      new nasal model did not differ significantly from Miljeteig and Hoffstein's
      original model, z = -0.16, p < 0.90. The best predictors for the nasal mask group
      were AHI, lowest SaO2, and neck size, whereas the top predictors in the oronasal
      group were AHI and lowest SaO2. CONCLUSION: Our data show that predictive models
      of CPAP that take into account mask style can significantly improve the formula's
      accuracy. Most of the past models likely focused on model development with nasal
      masks (mask style used for model development was not typically reported in
      previous investigations) and are not well suited for patients using an oronasal
      interface. Our new oronasal CPAP prediction equation produced significantly
      improved performance compared to the well-known Miljeteig and Hoffstein formula
      in patients titrated on CPAP with an oronasal mask and was also significantly
      related to laboratory determined optimal CPAP.

PMID- 27878545
TI  - Probability of foliar injury for Acer sp. based on foliar fluoride
      concentrations.
AB  - Fluoride is considered one of the most phytotoxic elements to plants, and
      indicative fluoride injury has been associated over a wide range of foliar
      fluoride concentrations. The aim of this study was to determine the probability
      of indicative foliar fluoride injury based on Acer sp. foliar fluoride
      concentrations using a logistic regression model. Foliage from Acer nedundo, Acer
      saccharinum, Acer saccharum and Acer platanoides was collected along a distance
      gradient from three separate brick manufacturing facilities in southern Ontario
      as part of a long-term monitoring programme between 1995 and 2014. Hydrogen
      fluoride is the major emission source associated with the manufacturing
      facilities resulting with highly elevated foliar fluoride close to the facilities
      and decreasing with distance. Consistent with other studies, indicative fluoride
      injury was observed over a wide range of foliar concentrations (9.9-480.0 MUg F-
      g-1). The logistic regression model was statistically significant for the Acer
      sp. group, A. negundo and A. saccharinum; consequently, A. negundo being the most
      sensitive species among the group. In addition, A. saccharum and A. platanoides
      were not statistically significant within the model. We are unaware of published
      foliar fluoride values for Acer sp. within Canada, and this research provides
      policy maker and scientist with probabilities of indicative foliar injury for
      common urban Acer sp. trees that can help guide decisions about emissions
      controls. Further research should focus on mechanisms driving indicative fluoride
      injury over wide ranging foliar fluoride concentrations and help determine foliar
      fluoride thresholds for damage.

PMID- 27878546
TI  - Investigation of antibiotics in health care wastewater in Ho Chi Minh City,
      Vietnam.
AB  - Hospital wastewater contains huge amounts of hazardous pollutants which are being
      discharged daily to environment with or without treatment. Antibiotics were among
      the important group of pharmaceuticals considered as a potential source of health
      risk for human and other living creatures. Although the investigations about the
      existence of antibiotics in hospital wastewater have gained concern for
      researchers in many countries, there is only one research conducted in Hanoi
      Vietnam. Hence, in this study, investigations have been done to fulfill the
      requirement of real situation in Vietnam by accomplishing survey for 39 health
      care facilities in Ho Chi Minh City. As results, seven popular antibiotics were
      detected to exist in all samples such as sulfamethoxazole (2.5 +/- 1.9 MUg/L),
      norfloxacin (9.6 +/- 9.8 MUg/L), ciprofloxacin (5.3 +/- 4.8 MUg/L), ofloxacin
      (10.9 +/- 8.1 MUg/L), erythromycin (1.2 +/- 1.2 MUg/L), tetracycline (0.1 +/- 0.0
      MUg/L), and trimethoprim (1.0 +/- 0.9 MUg/L). On the other hand, survey also
      showed that only 64% of health care facilities using conventional activate sludge
      (AS) processes in wastewater treatment plants (WWTPs). As a consequence, basic
      environmental factors (BOD5, COD, TSS, NH4+-N, or total coliforms) were not
      effectively removed from the hospital wastewater due to problems relating to
      initial design or operational conditions. Therefore, 18% effluent samples of the
      surveyed WWTPs have exceeded the national standard limits (QCVN 28:2010, level
      B).

PMID- 27878547
TI  - Transcatheter closure of paravalvular leaks: state of the art.
AB  - Paravalvular leak (PVL) is a serious complication after surgical valve
      replacement or after transcatheter aortic valve replacement. Approximately 1-5%
      of PVLs can lead to serious clinical consequences, including congestive heart
      failure and/or haemolytic anaemia. For years, surgical re-intervention has been
      considered the treatment of choice for symptomatic patients with PVLs. However,
      surgical re-intervention is associated with a high risk of morbidity and
      mortality. Transcatheter PVL (TPVL) closure is a less invasive alternative to
      surgical re-intervention. The safety and feasibility of TPVL closure has been
      confirmed in several registries and a meta-analysis.In this review, we discuss
      the clinical implications and diagnosis of PVLs, technical considerations for
      TPVL, execution of the procedure and assessment of the results.

PMID- 27878548
TI  - Contemporary use of arterial and venous conduits in coronary artery bypass
      grafting: anatomical, functional and clinical aspects.
AB  - Although the benefits of using the left internal mammary artery to bypass the
      left anterior descending artery (LAD) have been extensively ascertained, freedom
      from major cardiovascular events and survival after coronary artery bypass
      grafting (CABG) also correlate with the completeness of revascularisation. Hence,
      careful selection of the second-best graft conduit is crucial for CABG success.
      The more widespread use of saphenous vein grafts contrasts with the well-known
      long-term efficacy of multiple arterial grafting, which struggles to emerge as
      the procedure of choice due to concerns over increased technical difficulties and
      higher risk of postoperative complications. Conduit choice is at the discretion
      of the operator instead of being discussed by the heart team, where cardiologists
      are not usually engaged in such decisions due to a hypothetical lack of technical
      knowledge. Furthermore, according to the ESC/EACTS guidelines, traditional CABG
      remains the gold standard for multi-vessel coronary artery disease with complex
      LAD stenosis, but hybrid procedures using percutaneous coronary intervention for
      non-LAD targets could combine the best of two worlds. With the aim of raising the
      cardiologist's awareness of the surgical treatment options, we provide a
      comprehensive overview of the anatomical, functional and clinical aspects guiding
      the decision-making process in CABG strategy.

PMID- 27878549
TI  - Fluoroscopic freehand and electromagnetic-guided targeting system for distal
      locking screws of humeral intramedullary nail.
AB  - PURPOSE: The current techniques used to lock distal screws for the nailing of
      long bone fractures expose the surgeons, radiologists and patients to a hearty
      dose of ionizing radiation. The SureshotTM Distal Targeting System is a new
      technique that, with the same results, allows for shorter surgery times and,
      consequently, less exposure to radiation. MATERIALS AND METHODS: The study was
      performed on 59 patients (34 males and 25 females) with a simple humerus fracture
      diagnosis, type 1.2.A according to the AO classification, who were divided into
      two groups. Group 1 was treated with ante-grade intramedullary nailing with
      distal locking screws inserted with a freehand technique. Group 2 was treated
      with the intramedullary nail using the SureshotTM Distal Targeting System. Two
      intra-operative time parameters were evaluated in both groups: the time needed
      for the positioning of the distal locking screws and the time of exposure to
      ionizing radiations during this procedure. RESULTS: Group 2 showed a lower
      average distal locking time compared to group 1 (645.48" vs. 1023.57") and also a
      lower average time of exposure to ionizing radiation than in group 1 (4.35" vs.
      28.96"). CONCLUSION: The SureshotTM Distal Targeting System has proven to be
      equally effective when compared to the traditional techniques, with the added
      benefits of a significant reduction in both surgical time and risk factors
      related to the exposure to ionizing radiation for all the operating room staff
      and the patient.

PMID- 27878550
TI  - Diverticulitis: a comprehensive review with usual and unusual complications.
AB  - : Diverticulitis is characterized by inflammation of the outpouchings of the
      bowel wall. Imaging findings of diverticulitis include edematous thickening of
      the bowel wall with inflammatory changes within the adjacent mesenteric fat.
      Uncomplicated diverticulitis can be treated conservatively; however, complicated
      diverticulitis may not be responsive to medical treatment and life-threatening
      conditions may occur. In this review, we aimed to illustrate the ultrasonography
      (US) and computed tomography (CT) features of diverticulitis and its
      complications including perforation, phlegmon, abscess, ascending septic
      thrombophlebitis (phylephlebitis), bleeding, intestinal obstruction, and fistula.
      TEACHING POINTS: * Complications of diverticulitis may be highly variable. * It
      may be difficult to diagnose diverticulitis as underlying cause of severe
      complications. * MDCT is essential for the primary diagnosis of the acute
      diverticulitis and its complications.

PMID- 27878551
TI  - Interactions of GST Polymorphisms in Air Pollution Exposure and Respiratory
      Diseases and Allergies.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize the evidence from
      recently published original studies investigating how glutathione S-transferase
      (GST) gene polymorphisms modify the impact of air pollution on asthma, allergic
      diseases, and lung function. RECENT FINDINGS: Current studies in epidemiological
      and controlled human experiments found evidence to suggest that GSTs modify the
      impact of air pollution exposure on respiratory diseases and allergies. Of the
      nine articles included in this review, all except one identified at least one
      significant interaction with at least one of glutathione S-transferase pi 1
      (GSTP1), glutathione S-transferase mu 1 (GSTM1), or glutathione S-transferase
      theta 1 (GSTT1) genes and air pollution exposure. The findings of these studies,
      however, are markedly different. This difference can be partially explained by
      regional variation in the exposure levels and oxidative potential of different
      pollutants and by other interactions involving a number of unaccounted
      environment exposures and multiple genes. Although there is evidence of an
      interaction between GST genes and air pollution exposure for the risk of
      respiratory disease and allergies, results are not concordant. Further
      investigations are needed to explore the reasons behind the discordancy.

PMID- 27878552
TI  - Strength and Aerobic Exercises Improve Spatial Memory in Aging Rats Through
      Stimulating Distinct Neuroplasticity Mechanisms.
AB  - Aging is associated with impaired cognition and memory and increased
      susceptibility to neurodegenerative disorders. Physical exercise is
      neuroprotective; however, the major evidence of this effect involves studies of
      only aerobic training in young animals. The benefits of other exercise protocols
      such as strength training in aged animals remains unknown. Here, we investigated
      the effect of aerobic and strength training on spatial memory and hippocampal
      plasticity in aging rats. Aging Wistar rats performed aerobic or strength
      training for 50 min 3 to 4 days/week for 8 weeks. Spatial memory and neurotrophic
      and glutamatergic signaling in the hippocampus of aged rats were evaluated after
      aerobic or strength training. Both aerobic and strength training improved
      cognition during the performance of a spatial memory task. Remarkably, the
      improvement in spatial memory was accompanied by an increase in synaptic
      plasticity proteins within the hippocampus after exercise training, with some
      differences in the intracellular functions of those proteins between the two
      exercise protocols. Moreover, neurotrophic signaling (CREB, BDNF, and the P75NTR
      receptor) increased after training for both exercise protocols, and aerobic
      exercise specifically increased glutamatergic proteins (NMDA receptor and PSD
      95). We also observed a decrease in DNA damage after aerobic training. In
      contrast, strength training increased levels of PKCalpha and the proinflammatory
      factors TNF-alpha and IL-1beta. Overall, our results show that both aerobic and
      strength training improved spatial memory in aging rats through inducing distinct
      molecular mechanisms of neuroplasticity. Our findings extend the idea that
      exercise protocols can be used to improve cognition during aging.

PMID- 27878555
TI  - Laparoscopic distal pancreatectomy in elderly patients: is it safe?
AB  - BACKGROUND: Laparoscopic distal pancreatectomy (LDP) appears to be safe and
      effective as open distal pancreatectomy (ODP) for benign or borderline malignant
      lesion. However, studies comparing LDP with ODP in elderly patients are limited.
      The purpose of this study is to compare the clinical outcomes of these two
      several approaches in elderly patients. METHODS: A retrospective analysis was
      carried out by comparing laparoscopic (n = 7) and open (n = 15) distal
      pancreatectomy in elderly patients performed at the University of Naples
      "Federico II" and University of Perugia between January 2012 and December 2015.
      Demographic data, operative and postoperative outcomes were analyzed. RESULTS:
      Demographic and tumor characteristics of laparoscopic and ODP were similar. There
      were also no significant differences in operating room time. Patients undergoing
      LDP had lower blood loss, first flatus time, diet start time and postoperative
      hospital stay. There were no significant differences in complication rates or 90
      day mortality. DISCUSSION: LDP is safe and feasible as ODP in selected elderly
      patients.

PMID- 27878554
TI  - The Involvement of the Decrease of Astrocytic Wnt5a in the Cognitive Decline in
      Minimal Hepatic Encephalopathy.
AB  - Wnt signaling plays a key role in neuroprotection and synaptic plasticity. We
      speculate that the impairment of Wnt signaling may mediate astrocytic
      neurotrophins (NTs) production and the impairment of Wnt signaling to astrocytic
      NTs production contributes to the pathogenesis of minimal hepatic encephalopathy
      (MHE). Here, we found that induction of astrocytic NTs synthesis was by Wnt5a via
      the calcium/calmodulin-sensitive protein kinase II (CaMK II)-cAMP-response
      element-binding protein (CREB) pathway in PCAs. The decrease of spatial learning
      and memory and downregulation of astrocytic BDNF and NT-3 were reversed by Wnt5a
      in MHE rat model. The increased association between CaMK II and CREB followed by
      phosphorylation of CREB in response to Wnt5a stimulation was suppressed in the
      MHE rat model. Our results highlight a novel pathogenesis of the contribution of
      downregulation of NTs to the inhibition of the interaction between Wnt5a and
      Frizzled-2 in astrocytes in MHE.

PMID- 27878553
TI  - Magnesium Sulfate Provides Neuroprotection in Eclampsia-Like Seizure Model by
      Ameliorating Neuroinflammation and Brain Edema.
AB  - Eclampsia is a hypertensive disorder of pregnancy that is defined by the new
      onset of grand mal seizures on the basis of preeclampsia and a leading cause of
      maternal and fetal mortality worldwide. Presently, magnesium sulfate (MgSO4) is
      the most effective treatment, but the mechanism by which MgSO4 prevents eclampsia
      has yet to be fully elucidated. We previously showed that systemic inflammation
      decreases the seizure threshold in a rat eclampsia-like model, and MgSO4
      treatment can decrease systemic inflammation. Here, we hypothesized that MgSO4
      plays a neuroprotective role in eclampsia by reducing neuroinflammation and brain
      edema. Pregnant Sprague-Dawley rats were given an intraperitoneal injection of
      pentylenetetrazol following a tail vein injection of lipopolysaccharide to
      establish the eclampsia-like seizure model. Seizure activity was assessed by
      behavioral testing. Neuronal loss in the hippocampal CA1 region (CA1) was
      detected by Nissl staining. Cerebrospinal fluid levels of S100-B and ferritin,
      indicators of neuroinflammation, were detected by enzyme-linked immunosorbent
      assay, and ionized calcium binder adapter molecule 1 (Iba-1, a marker for
      microglia) and glial fibrillary acid protein (GFAP, a marker for astrocytes)
      expression in the CA1 area was determined by immunofluorescence staining. Brain
      edema was measured. Our results revealed that MgSO4 effectively attenuated
      seizure severity and CA1 neuronal loss. In addition, MgSO4 significantly reduced
      cerebrospinal fluid levels of S100-B and ferritin, Iba-1 and GFAP activation in
      the CA1 area, and brain edema. Our results indicate that MgSO4 plays a
      neuroprotective role against eclampsia-like seizure by reducing neuroinflammation
      and brain edema.

PMID- 27878556
TI  - Venous anomalies of the axilla: a single-institution experience.
AB  - AIM: Surgical treatment is still the cornerstone in the treatment of breast
      cancer, a very common neoplasia, particularly affecting the female elderly
      population. Axillary dissection is crucial in the treatment of some tumours, but
      variations in axillary vessels anatomy are poorly described in standard anatomy
      and surgical textbook. We aimed to describe anatomical variations in axillary
      vessels found in our institutional experience. PATIENTS AND METHODS: A
      prospective 3-year study was conducted in our institution from January 2012 to
      December 2014. Sixty-one consecutive axillary lymph node dissections (ALNDs) were
      performed in 61 patients who underwent surgery for stage II and III invasive
      breast cancer. Anatomical details of axillary vascular anatomy and its variations
      have been evaluated, described and stored in a prospective database. RESULTS:
      Sixty-one ALNDs have been performed in the study period. The anatomy of lateral
      thoracic vein, angular vein and axillary vein was studied and compared with
      standard anatomical description. Eighteen percentage of venous variations were
      found out of the 61 dissection performed. CONCLUSIONS: Vascular anatomy of axilla
      is complex and variable. A better knowledge of all possible variations might be
      helpful in preventing injuries during ALND.

PMID- 27878557
TI  - Simple reaction time for broadband sounds compared to pure tones.
AB  - Although many studies have explored the relation between reaction time (RT) and
      loudness, including effects of intensity, frequency, and binaural summation,
      comparable work on spectral summation is rare. However, most real-world sounds
      are not pure tones and typically have bandwidths covering several critical bands.
      Since comparing to a 1-kHz pure tone, the reference tone, is important for
      loudness measurement and standardization, the present work focuses on comparing
      RTs for broadband noise to those for 1-kHz pure tones in three experiments using
      different spectral and binaural configurations. The results of Experiments 1 and
      2 yield good quantitative agreement with spectral loudness summation models for
      moderate and high sound pressure levels, measured using both pink noise covering
      almost the entire hearing range and bandpass-filtered pink noise with different
      center frequencies. However, at lower levels, the RT measurements yield an
      interaction of level and bandwidth, which is not in line with loudness scaling
      data. In Experiment 3, which investigated the binaural summation of broadband
      sounds, the binaural gain for white noise was determined to be 9 dB, which is
      somewhat larger than what had been found in previous RT measurements using 1-kHz
      pure tones.

PMID- 27878558
TI  - Discrimination of face gender and expression under dual-task conditions.
AB  - In order to test whether expression and gender can be attended to simultaneously
      without a cost in accuracy four experiments were carried out using a dual gender
      expression task with male and female faces showing different emotional
      expressions that were backward masked by emotionally neutral faces. In the dual
      facial condition the participants had to report both the gender and the
      expression of the targets. In two control conditions the participant reported
      either the gender or the expression of the face and indicated whether a
      surrounding frame was continuous or discontinuous. In Experiments 1-3, with angry
      and happy targets, asymmetric interference was observed. Gender discrimination,
      but no expression discrimination, was impaired in the dual-facial condition
      compared to the corresponding control. This effect was obtained with a between
      subjects design in Experiment 1, with a within-subjects design in Experiment 2,
      and with androgynous face masks in Experiment 3. In Experiments 4a and 4b
      different target combinations were tested. No decrement of performance in the
      dual-facial task was observed for either gender or expression discrimination with
      fearful-disgusted (Experiment 4a) or fearful-happy faces (Experiment 4b). We
      conclude that the ability to attend simultaneously to gender and expression cues
      without a decrement in performance depends on the specific combination of
      expressions to be differentiated between. Happy and angry expressions are usually
      directed at the perceiver and command preferential attention. Under conditions of
      restricted viewing such as those of the present study, discrimination of these
      expressions is prioritized leading to impaired discrimination of other facial
      properties such as gender.

PMID- 27878560
TI  - Clinical and etiological profile of epilepsy in elderly: a hospital-based study
      from rural India.
AB  - To determine the clinical profile and etiology of epilepsy in elderly patients in
      rural population of India which is in a phase of demographic transition with
      steadily growing geriatric population. A cross-sectional, prospective, hospital
      based clinicoepidemiological study was performed from October 2014 to November
      2015. Patients having onset of epilepsy after 60 years were incorporated in the
      study. We excluded the acute symptomatic seizures. One hundred and ten patients
      were enrolled and were divided into three standard subgroups: subgroup A (aged 60
      70), subgroup B (aged 71-80), and subgroup C (aged 81-90). Out of 110 patients,
      72 (65.45%) were male and 38 (34.54%) were female. The most common etiology was
      cerebrovascular disease (46.36%), followed by focal cerebral calcifications
      single or multiple (11.81%), tumors (9.09%), trauma (6.36%) dementias (6.36%) and
      unknown (16.63%). In our study, the frequency of epilepsy decreases with
      advancing age which was 77.27% in group A (less than 70 years), 16.36% in group B
      and 6.36% in group C (70-90 years).The most common type of seizure in the group
      studied was focal 59.09% followed by generalized seizures 37.27%. Hypertension
      was the most common co-morbidity found in 40 (36.36%) patients. The present study
      proposes that epilepsy in the elderly patients have etiological relationship with
      stroke, focal cerebral calcifications, tumors and dementias. CNS infections
      account for a significant number of cases of remote symptomatic epilepsy in
      elderly in our region where neurocysticercosis is endemic.

PMID- 27878559
TI  - Impact of Drug Manipulation on Seizure Freedom in Adults with Uncontrolled
      Epilepsy: A Prospective Controlled Study in Rural China.
AB  - INTRODUCTION: It has been suggested that uncontrolled epilepsy might not
      necessarily equate to drug resistance when antiepileptic drugs (AEDs) are used at
      relatively low doses, a practice frequently observed in rural areas of China.
      OBJECTIVE: To assess the clinical benefits of further drug manipulation in this
      situation, we prospectively followed up the outcomes of patients with
      uncontrolled epilepsy while taking relatively low doses of AEDs. METHODS: The
      study included patients aged 16 years and older with uncontrolled epilepsy and
      who were receiving at least one AED at a dosage below 50% of the World Health
      Organization (WHO) defined daily dose (DDD) (50% DDD) (Group 1). Patients with
      drug-resistant epilepsy were included for comparison (Group 2). Both groups were
      followed-up for at least 2 years. Seizure outcomes after further drug
      manipulations were recorded at the last follow-up. RESULTS: A total of 197
      patients (55.3% male) were included in Group 1 and 32 (46.9% male) in Group 2;
      their mean duration of follow-up was 28.85 +/- 1.90 and 30.91 +/- 2.04 months,
      respectively. At the last follow-up, 16.8% (33/197) of patients in Group 1 had
      become seizure-free compared with none in Group 2 (p < 0.001). Seventeen of 93
      (18.3%) patients in Group 1 became seizure free after increasing the dosage of
      baseline AED(s) alone. Only 5.5% (3/55) of patients who had failed to respond to
      an AED at >=50% DDD at baseline became seizure free compared with 21.1% (30/142)
      who did not have such a history (p = 0.001). The number of AEDs taken at a dosage
      below 50% DDD at baseline was not associated with seizure outcome. CONCLUSIONS:
      Uncontrolled epilepsy could become controlled in a substantial proportion of
      patients by dose increase alone, particularly if there is no history of drug
      failure at >=50% DDD.

PMID- 27878561
TI  - Pseudotumoral brain lesions: MRI review.
AB  - Single or multiple space-occupying lesions on brain MRI, with or without contrast
      enhancement and/or perilesional oedema, evoke a neoplastic origin. However, a
      multitude of non-neoplastic disorders can simulate cerebral neoplasia. In this
      review, we will discuss the MRI characteristics of non-neoplastic disorders that
      can mimic cerebral neoplasia. Distinguishing MRI characteristics are discussed
      for each of these non-neoplastic disorders.

PMID- 27878563
TI  - Asymptomatic Elevated BP and the Hypertensive Insurgency.

PMID- 27878565
TI  - Challenges and Prospect of Non-aqueous Non-alkali (NANA) Metal-Air Batteries.
AB  - Non-aqueous non-alkali (NANA) metal-air battery technologies promise to provide
      electrochemical energy storage with the highest specific energy density. Metal
      air battery technology is particularly advantageous being implemented in long
      range electric vehicles. Up to now, almost all the efforts in the field are
      focused on Li-air cells, but other NANA metal-air battery technologies emerge.
      The major concern, which the research community should be dealing with, is the
      limited and rather poor rechargeability of these systems. The challenges we are
      covering in this review are related to the initial limited discharge capacities
      and cell performances. By comprehensively reviewing the studies conducted so far,
      we show that the implementation of advanced materials is a promising approach to
      increase metal-air performance and, particularly, metal surface activation as a
      prime achievement leading to respectful discharge currents. In this review, we
      address the most critical areas that need careful research attention in order to
      achieve progress in the understanding of the physical and electrochemical
      processes in non-aqueous electrolytes applied in beyond lithium and zinc air
      generation of metal-air battery systems.

PMID- 27878564
TI  - The role of B7 family costimulatory molecules and indoleamine 2,3-dioxygenase in
      primary Sjogren's syndrome and systemic sclerosis.
AB  - B7 costimulatory molecules are present on antigen-presenting cells (APCs) and
      influence intracellular expression of indoleamine 2,3-dioxygenase (IDO), a
      molecule with important immunoregulatory functions. We determined the frequency
      of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2
      molecules, and that of CD3+ and CD4+ T cells expressing the corresponding CD28,
      CTLA-4, PD-1, and ICOS receptors in peripheral blood samples of 20 healthy adults
      and 9 SSc and 15 pSS patients using flow cytometry. We also examined the
      intracellular expression of IDO. The expression of CD28 was lower in both SSc and
      pSS patients. The frequency of CTLA-4 was increased in pSS. The expression of
      ICOS, a stimulator of T cell activation, was elevated in pSS, but not in SSc,
      while that of its corresponding costimulatory molecule, B7-H2, was strongly
      decreased in SSc compared to controls. The frequency of PD-1 expressing T
      lymphocytes was decreased in both pSS and SSc. The frequency of IDO-expressing
      APCs, as well as intracellular IDO content in T cells was higher in pSS than in
      controls. Our investigation identified a number of differences in B7
      costimulation between SSc and pSS patients which may play a role in the distinct
      pathogenesis and clinical features of these autoimmune disorders.

PMID- 27878566
TI  - Pharmacokinetic and Pharmacodynamic Properties of Faster-Acting Insulin Aspart
      versus Insulin Aspart Across a Clinically Relevant Dose Range in Subjects with
      Type 1 Diabetes Mellitus.
AB  - BACKGROUND: Absorption of current rapid-acting insulins is too slow for patients
      with diabetes mellitus to achieve optimal postprandial glucose control. Faster
      acting insulin aspart (faster aspart) is insulin aspart in a new formulation with
      faster early absorption. We compared the pharmacokinetic/pharmacodynamic
      properties of faster aspart and insulin aspart across a clinically relevant dose
      range. METHODS: In this randomised, double-blind, crossover trial, 46 subjects
      with type 1 diabetes mellitus received single subcutaneous doses of faster aspart
      and insulin aspart at 0.1, 0.2 (repeated three times to estimate within-subject
      variability) and 0.4 U/kg in a euglycaemic clamp setting (target 5.5 mmol/L).
      RESULTS: Consistently for the three doses, faster aspart demonstrated faster
      onset and greater early absorption and glucose-lowering effect versus insulin
      aspart. Across all three doses, onset of appearance occurred approximately twice
      as fast (approximately 5 min earlier) and early insulin exposure (AUCIAsp,0
      30min) was approximately 1.5- to 2-fold greater for faster aspart versus insulin
      aspart. Likewise, onset of action occurred approximately 5 min faster and early
      glucose-lowering effect (AUCGIR,0-30min) was approximately 1.5- to 2-fold larger
      for faster aspart versus insulin aspart. Relative bioavailability was
      approximately 100% and total glucose-lowering effect was similar for faster
      aspart versus insulin aspart. Dose-concentration and dose-response relationships
      were comparable between faster aspart and insulin aspart. Within-subject
      variability in glucose-lowering effect was low for faster aspart (coefficient of
      variation approximately 20%) and not significantly different from insulin aspart.
      CONCLUSION: The faster onset and greater early insulin exposure and glucose
      lowering effect with faster aspart versus insulin aspart are preserved across a
      broad range of doses and consistently observed from day to day. CLINICALTRIALS.
      GOV IDENTIFIER: NCT02033239.

PMID- 27878568
TI  - Bioremoval of humic acid from water by white rot fungi: exploring the removal
      mechanisms.
AB  - Twelve white rot fungi (WRF) strains were screened on agar plates for their
      ability to bleach humic acid (HA). Four fungal strains were selected and tested
      in liquid media for removal of HA. Bioremediation was investigated by HA color
      removal and changes in the concentration and molecular size distribution of HA by
      size exclusion chromatography. Trametes versicolor and Phanerochaete
      chrysosporium showed the highest HA removal efficiency, reaching about 80%.
      Laccase and manganese peroxidase were measured as extracellular enzymes and their
      relation to the HA removal by WRF was investigated. Results indicated that
      nitrogen limitation could enhance the WRF extracellular enzyme activity, but did
      not necessarily increase the HA removal by WRF. The mechanism of bioremediation
      by WRF was shown to involve biosorption of HA by fungal biomass and degradation
      of HA to smaller molecules. Also, contradicting previous reports, it was shown
      that the decolorization of HA by WRF could not necessarily be interpreted as
      degradation of HA. Biosorption experiments revealed that HA removal by fungal
      biomass is dependent not only on the amount of biomass as the sorbent, but also
      on the fungal species. The involvement of cytochrome P450 (CYP) enzymes was
      confirmed by comparing the HA removal capability of fungi with and without the
      presence of a CYP inhibitor. The ability of purified laccase from WRF to solely
      degrade HA was proven and the importance of mediators was also demonstrated.

PMID- 27878567
TI  - Drug Interactions Between Peficitinib, an Orally Administered, Once-Daily Janus
      Kinase Inhibitor, and Rosuvastatin in Healthy Subjects.
AB  - BACKGROUND AND OBJECTIVE: Peficitinib is an orally administered, once-daily Janus
      kinase inhibitor in development for the treatment of rheumatoid arthritis.
      Peficitinib and its major metabolite H2 inhibit the hepatic uptake transporter
      organic anion transporting polypeptide 1B1 (OATP1B1) in vitro. This article
      reports a clinical study evaluating the effects of peficitinib on the
      pharmacokinetics of rosuvastatin, a substrate for the OATP1B1 transporter, and
      vice versa. METHODS: In an open-label, single-sequence clinical study, 24 healthy
      adults of East Asian and non-East Asian origin received a single dose of
      rosuvastatin 10 mg on days 1 and 10. On days 5-13, subjects received a daily dose
      of 150 mg peficitinib. Serial blood samples for pharmacokinetic assessment of
      rosuvastatin were collected up to 96 h post-dose on days 1 and 10, and for
      peficitinib were collected up to 24 h post-dose on days 9 and 10. RESULTS: Co
      administration of peficitinib with rosuvastatin increased rosuvastatin area under
      the concentration-time curve (AUC) and maximum plasma concentration (C max) by 18
      and 15%, respectively and increased peficitinib AUC and C max by 16 and 28%,
      respectively. In East Asian (n = 6) vs. non-East Asian subjects (n = 18),
      peficitinib mean AUC for a dosing interval was 45 and 21% higher, and mean C max
      was 67 and 34% higher, when administered alone or with rosuvastatin. Peficitinib
      was well tolerated with few adverse events overall. CONCLUSION: In this study,
      once-daily oral administration of peficitinib had no clinically significant
      effect on the pharmacokinetics of rosuvastatin, a probe substrate for OATP1B1.
      Therefore, it is unlikely that peficitinib will have a clinically significant
      effect on the exposure of other substrates for OATP1B1. CLINICALTRIALS. GOV
      NUMBER: NCT01959399.

PMID- 27878569
TI  - Assay of hemoglobin A1c using lectin from Aleuria aurantia.
AB  - Hemoglobin A1c (HbA1c) has an N-terminal fructosyl valine on the beta-chain, and
      this modification is caused by the non-enzymatic glycosylation of hemoglobin
      (Hb). The relative concentration ratio of HbA1c to total Hb is an important
      biomarker for the diagnosis of diabetes. HbA1c-binding lectins were screened from
      29 sources of lectin, and the lectin from Aleuria aurantia (AAL) was revealed to
      have higher affinity to HbA1c than to Hb. The concentration of HbA1c was
      determined by lectin-based enzyme-linked immunosorbent assay (ELISA) using the
      AAL lectin. Higher reproducibility of the assay was observed at 4  degrees C than
      at 25 and 37  degrees C. This observation is consistent with the known
      temperature-dependent behavior of lectins. Preincubation of HbA1c with an anti
      HbA1c antibody inhibited the binding, suggesting that AAL binds to the N-terminal
      fructosyl valine epitope of HbA1c. Higher inhibitory effect was observed for 10
      mM D-fructose than for the same concentrations of L-fucose, D-fucose, or D
      glucose.

PMID- 27878570
TI  - Synchronous double cancers of primary hepatocellular carcinoma and
      cholangiolocellular carcinoma: a case report.
AB  - Synchronous double cancers consisting of hepatocellular carcinoma (HCC) and
      cholangiolocellular carcinoma (CoCC) are extremely rare. We herein report a
      surgical case of synchronous double cancers in a patient with primary HCC and
      CoCC. A 45-year-old man with hepatitis B was admitted to our hospital with
      hepatic tumors. The level of protein induced by vitamin K antagonist (PIVKA-II)
      was found to be elevated. Computed tomography (CT) revealed a 23-mm tumor with
      early-phase enhancement and late-phase washout in the 6th segment of the liver,
      and a 10-mm tumor with slight early-phase enhancement and late-phase washout in
      the 7th segment of the liver. Magnetic resonance imaging (MRI) revealed that the
      two tumors in the 6th and 7th segments showed low intensity on T1-weighted images
      and high intensity on T2-weighted images. Based on those preoperative
      examinations, the liver tumors were diagnosed as multiple primary hepatocellular
      carcinomas. The patient underwent a posterior segmentectomy. A histopathological
      examination revealed that the tumor of the 6th segment of the liver was
      moderately differentiated HCC, and that the tumor of the 7th segment of the liver
      was CoCC. The postoperative course was uneventful. However, lymph node recurrence
      was observed 6 months later and the patient died 20 months after surgery. There
      are only six reported surgical cases of synchronous double primary liver cancers
      consisting of HCC and CoCC. We are of the opinion that curative resection may be
      an effective treatment for double cancer consisting of HCC and CoCC, and that it
      may provide long-term survival.

PMID- 27878571
TI  - A case of a horseshoe appendix.
AB  - Anomalies of the appendix are extremely rare, and a horseshoe appendix is even
      rarer. A literature search has revealed only five reported cases. In this report,
      we present a case of a horseshoe appendix.A 78-year-old man was referred for
      further examination following a positive fecal occult blood test. A mass in his
      ascending colon was detected on colonoscopy, while computed tomography showed
      that it was connected to the appendix. Tumor invasion derived from the ascending
      colon or appendix was suspected. We diagnosed ascending colon cancer prior to
      laparoscopic ileocecal resection. Macroscopic findings showed that the appendix
      connected to the back side of the mass, while microscopic findings showed that
      the mucosa and submucosa were continuous from the appendiceal orifice in the
      cecum to the other orifice in the ascending colon, where a type 1 tumor was
      observed on the orifice. We eventually diagnosed the patient with tubulovillous
      adenoma and a horseshoe appendix.A horseshoe appendix communicates with the colon
      at both ends and is supplied by a single fan-shaped mesentery. Cases are
      classified by the disposal of the mesentery and the location of the orifice.
      Anatomical anomalies should be considered despite the rarity of horseshoe
      appendices.

PMID- 27878572
TI  - A comparison of two insulin infusion protocols in the medical intensive care unit
      by continuous glucose monitoring.
AB  - BACKGROUND: Achieving good glycemic control in intensive care units (ICU)
      requires a safe and efficient insulin infusion protocol (IIP). We aimed to
      compare the clinical performance of two IIPs (Leuven versus modified Yale
      protocol) in patients admitted to medical ICU, by using continuous glucose
      monitoring (CGM). This is a pooled data analysis of two published prospective
      randomized controlled trials. CGM monitoring was performed in 57 MICU patients
      (age 64 +/- 12 years, APACHE-II score 28 +/- 7, non-diabetic/diabetic: 36/21).
      The main outcome measures were percentage of time in normoglycemia (80-110 mg/dl)
      and in hypoglycemia (<60 mg/dl), and glycemic variability (standard deviation,
      coefficient of variation, mean amplitude of glucose excursions, mean of daily
      differences). RESULTS: Twenty-two subjects were treated using the Leuven protocol
      and 35 by the Yale protocol; >63,000 CGM measurements were available. The
      percentage of time in normoglycemia (80-110 mg/dl) was higher (37 +/- 15 vs. 26
      +/- 11%, p = 0.001) and percentage of time spent in hypoglycemia was lower (0[0
      2] vs. 5[1-8]%, p = 0.001) in the Yale group. Median glycemia did not differ
      between groups (118[108-128] vs. 128[106-154] mg/dl). Glycemic variability was
      less pronounced in the Yale group (median SD 28[21-37] vs. 47[31-71] mg/dl, p =
      0.001; CV 23[19-31] vs. 36[26-50]%, p = 0.001; MODD 35[26-41] vs. 60[33-94]
      mg/dl, p = 0.001). However, logistic regression could not identify type of IIP,
      diabetes status, age, BMI, or APACHE-II score as independent parameters for
      strict glucose control. CONCLUSIONS: The Yale protocol provided better average
      glycemia, more time spent in normoglycemia, less time in hypoglycemia, and less
      glycemic variability than the Leuven protocol, but was not independently
      associated with strict glycemic control.

PMID- 27878573
TI  - Prognostic value of procalcitonin in patients after elective cardiac surgery: a
      prospective cohort study.
AB  - BACKGROUND: Procalcitonin (PCT) is a well-known prognostic marker after elective
      cardiac surgery. However, the impact of elevated PCT in patients with an
      initially uneventful postoperative course is still unclear. The aim of this study
      was to evaluate PCT levels as a prognostic tool for delayed complications after
      elective cardiac surgery. METHODS: A prospective study was performed in 751
      patients with an apparently uneventful postoperative course within the first 24 h
      after elective cardiac surgery. Serum PCT concentration was taken the morning
      after surgery. All patients were screened for the occurrence of delayed
      complications. Delayed complications were defined by in-hospital death, intensive
      care unit readmission, or prolonged length of hospital stay (>12 days). Odds
      ratios (OR) [with 95% confidence interval (CI)] were calculated by logistic
      regression analyses and adjusted for confounders. Predictive capacity of PCT for
      delayed complications was calculated by ROC analyses. The cutoff value of PCT was
      derived from the Youden Index calculation. RESULTS: Among 751 patients with an
      initially uneventful postoperative course, 117 patients developed delayed
      complications. Serum PCT levels the first postoperative day were significantly
      higher in these 117 patients (8.9 ng/ml) compared to the remaining 634 (0.9
      ng/ml; p < 0.001). ROC analyses showed that PCT had a high accuracy to predict
      delayed complications (optimal cutoff value of 2.95 ng/ml, AUC of 0.90,
      sensitivity 73% and specificity 97%). Patients with PCT levels above 2.95 ng/ml
      the first postoperative day had a highly increased risk of delayed complications
      (adjusted OR, 110.2; 95% CI 51.5-235.5; p < 0.001). CONCLUSIONS: A single
      measurement of PCT seems to be a useful tool to identify patients at risk of
      delayed complications despite an initially uneventful postoperative course.

PMID- 27878574
TI  - The Luminescent Inhomogeneity and the Distribution of Zinc Vacancy-Related
      Acceptor-Like Defects in N-Doped ZnO Microrods.
AB  - Vertically aligned N-doped ZnO microrods with a hexagonal symmetry were
      fabricated via the chemical vapor transport with abundant N2O as both O and N
      precursors. We have demonstrated the suppression of the zinc interstitial-related
      shallow donor defects and have identified the zinc vacancy-related shallow and
      deep acceptor states by temperature variable photoluminescence in O-rich growth
      environment. Through spatially resolved cathodoluminescence spectra, we found the
      luminescent inhomogeneity in the sample with a core-shell structure. The deep
      acceptor-isolated VZn and the shallow acceptor VZn-related complex or clusters
      mainly distribute in the shell region.

PMID- 27878575
TI  - Gate-Controlled WSe2 Transistors Using a Buried Triple-Gate Structure.
AB  - In the present paper, we show tungsten diselenide (WSe2) devices that can be
      tuned to operate as n-type and p-type field-effect transistors (FETs) as well as
      band-to-band tunnel transistors on the same flake. Source, channel, and drain
      areas of the WSe2 flake are adjusted, using buried triple-gate substrates with
      three independently controllable gates. The device characteristics found in the
      tunnel transistor configuration are determined by the particular geometry of the
      buried triple-gate structure, consistent with a simple estimation of the expected
      off-state behavior.

PMID- 27878577
TI  - Atom Diffusion and Evaporation of Free-Ended Amorphous SiOx Nanowires:
      Nanocurvature Effect and Beam-Induced Athermal Activation Effect.
AB  - Arresting effects of nanocurvature and electron beam-induced athermal activation
      on the structure changes at nanoscale of free-ended amorphous SiOx nanowire were
      demonstrated. It was observed that under in situ uniform electron beam
      irradiation in transmission electron microscope, the near surface atoms at the
      most curved free end of the nanowire preferentially vaporized or diffused to the
      less curved wire sidewall. The processing resulted in an intriguing axial
      shrinkage and an abnormal radial expansion of the wire. It was also observed that
      with the beam energy deposition rate being lowered, although both the diffusion
      and the evaporation slowed down, the processing transferred from an evaporation
      dominated status to a diffusion-dominated status. These results are crucial not
      only to the fundamental understanding but also to the technical controlling of
      the electron beam-induced structure change at nanoscale or nanoprocessing of low
      dimensional nanostructures.

PMID- 27878576
TI  - Improving the Photoelectric Characteristics of MoS2 Thin Films by Doping Rare
      Earth Element Erbium.
AB  - We investigated the surface morphologies, crystal structures, and optical
      characteristics of rare earth element erbium (Er)-doped MoS2 (Er: MoS2) thin
      films fabricated on Si substrates via chemical vapor deposition (CVD). The
      surface mopography, crystalline structure, light absorption property, and the
      photoelectronic characteristics of the Er: MoS2 films were studied. The results
      indicate that doping makes the crystallinity of MoS2 films better than that of
      the undoped film. Meanwhile, the electron mobility and conductivity of the Er
      doped MoS2 films increase about one order of magnitude, and the current-voltage
      (I-V) and the photoelectric response characteristics of the Er:MoS2/Si
      heterojunction increase significantly. Moreover, Er-doped MoS2 films exhibit
      strong light absorption and photoluminescence in the visible light range at room
      temperature; the intensity is enhanced by about twice that of the undoped film.
      The results indicate that the doping of MoS2 with Er can significantly improve
      the photoelectric characteristics and can be used to fabricate highly efficient
      luminescence and optoelectronic devices.

PMID- 27878578
TI  - The double guidewire approach for transcoronary pacing in a porcine model.
AB  - BACKGROUND: Transcoronary pacing is used for treatment of unheralded bradycardias
      in the setting of percutaneous coronary interventions (PCI). OBJECTIVES: In the
      present study we introduced a new concept - the double guidewire approach - for
      transcoronary pacing in a porcine model. METHODS: Transcoronary pacing was
      applied in 16 adult pigs under general anaesthesia in an animal catheterization
      laboratory. A special guidewire with electrical insulation by PTFE coating except
      for the distal part of the guidewire was positioned in the periphery of a
      coronary artery serving as the cathode. As the indifferent anode, an additional
      standard floppy tip guidewire was advanced into the proximal part of the same
      coronary vessel. The efficacy of double guidewire transcoronary pacing was
      assessed by measurement of threshold and impedance data and the magnitude of the
      epicardial electrogram compared with unipolar transcoronary pacing using a
      standard cutaneous patch electrode as indifferent anode. RESULTS: Transcoronary
      pacing was effective in all cases. Pacing thresholds obtained with the double
      guidewire technique (1.5 +/- 0.9 V) were similar to those obtained by standard
      unipolar transcoronary pacing with a cutaneous patch electrode (1.2 +/- 0.7 V)
      and unipolar transvenous pacing against the same cutaneous patch electrode (1.5
      +/- 1.0 V). Bipolar transvenous pacing yielded the lowest pacing threshold at 0.8
      +/- 0.4 V. CONCLUSIONS: Transcoronary pacing in the animal model with the novel
      "double guidewire approach" is a simple and effective pacing technique with
      comparable pacing thresholds obtained by standard unipolar transcoronary and
      transvenous pacing.

PMID- 27878581
TI  - Magnesium aminoclay-based transformation of Paenibacillus riograndensis and
      Paenibacillus polymyxa and development of tools for gene expression.
AB  - Members of the genus Paenibacillus are widespread facultative anaerobic,
      endospore-forming bacteria. Some species such as Paenibacillus riograndensis or
      Paenibacillus polymyxa fix nitrogen and may play an important role in agriculture
      to reduce mineral nitrogen fertilization in particular for non-legume plants. The
      genetic manipulation of Paenibacillus is an imperative for the functional
      characterization, e.g., of its plant growth-promoting activities and metabolism.
      This study showed that P. riograndensis and P. polymyxa can be readily
      transformed using physical permeation by magnesium aminoclays. By means of the
      fluorescent reporter genes gfpUV, mcherry, and crimson, a two-plasmid system
      consisting of a theta-replicating plasmid and a rolling circle-replicating
      plasmid was shown to operate in both species. Xylose-inducible and mannitol
      inducible fluorescent reporter gene expression was demonstrated in the compatible
      two-plasmid system by fluorescence-activated cell scanning. As a metabolic
      engineering application, the biotin requiring P. riograndensis was converted to a
      biotin-prototrophic strain based on mannitol-inducible expression of the biotin
      biosynthesis operon bioWAFDBI from Bacillus subtilis.

PMID- 27878580
TI  - Depressive symptom trajectories in the first 10 years of diabetes diagnosis:
      antecedent factors and link with future disability in Taiwan.
AB  - PURPOSE: This study identified depressive symptom trajectories in the years after
      diabetes diagnosis, examined factors that predict the probability for people
      following a specific trajectory, and investigated how the trajectories are
      associated with subsequent disability. METHODS: We drew data from a nationally
      representative survey in Taiwan to identify adults aged 50 and older diagnosed
      with diabetes; 487 patients newly diagnosed with diabetes during 1996-2007 were
      included. Time axis was set to zero when diabetes was first reported in any given
      wave in the survey, and data related to depressive symptoms after that were
      recorded. We used group-based semi-parametric mixture models to identify
      trajectories of depressive symptoms and multinomial logistic regressions to
      examine factors associated with the trajectories. RESULTS: Older adults with
      newly diagnosis of diabetes in Taiwan follow different trajectories of depressive
      symptoms over time. Being female, lower educated, not married/partnered, with
      lower self-rated health, hospitalizations, more limitations in physical function,
      less regular exercise before diagnosis, and not regularly using anti-diabetic
      medication at the beginning of their diagnosis were factors associated with
      increasing or high stable depressive symptom trajectories. Those who experienced
      high depressive symptoms were more likely than individuals with stable depressive
      symptoms to have physical limitations in the last follow-up interview.
      CONCLUSIONS: Depressive symptom trajectories after diabetes diagnosis were
      associated with select sociodemographic, health, and lifestyle factors before
      diagnosis, and also predicted subsequent disability. Risk groups identified in
      the present study may be used for personalized diabetes care that prevents
      diabetes-related distress and future disability.

PMID- 27878579
TI  - G protein coupled receptors signaling pathways implicate in inflammatory and
      immune response of rheumatoid arthritis.
AB  - INTRODUCTION: G protein-coupled receptors (GPCRs) are transmembrane receptor
      proteins, which allow the transfer of signals across the membrane. Rheumatoid
      arthritis (RA) is an autoimmune disease characterized by synovitis and
      accompanied with inflammatory and abnormal immune response. GPCRs signaling
      pathways play a significant role in inflammatory and immune response processes
      including RA. FINDINGS: In this review, we have focused on the advances in GPCRs
      signaling pathway implicating the inflammatory and immune response of RA. The
      signaling pathways of GPCRs-adenylyl cyclase (AC)-cyclic adenosine 3', 5'
      monophosphate (cAMP) include beta2 adrenergic receptors (beta2-ARs)-AC-cAMP
      signaling pathways, E-prostanoid2/4 (EP2/4)-AC-cAMP signaling pathways and so on.
      Regulatory proteins, such as G protein-coupled receptor kinases (GRKs) and beta
      arrestins, play important modulatory roles in GPCRs signaling pathway. GPCRs
      signaling pathway and regulatory proteins implicate the pathogenesis process of
      inflammatory and immune response. CONCLUSION: GPCRs-AC-cAMP signal pathways
      involve in the inflammatory and immune response of RA. Different signaling
      pathways are mediated by different receptors, such as beta2-AR, PGE2 receptor,
      chemokines receptor, and adenosine receptor. GRKs and beta-arrestins are crucial
      proteins in the regulation of GPCRs signaling pathways. The potential therapeutic
      targets as well as strategies to modulate GPCRs signaling pathway are new
      development trends.

PMID- 27878582
TI  - Chilli leaf curl virus-based vector for phloem-specific silencing of endogenous
      genes and overexpression of foreign genes.
AB  - Geminiviruses are the largest and most devastating group of plant viruses which
      contain ssDNA as a genetic material. Geminivirus-derived virus-induced gene
      silencing (VIGS) vectors have emerged as an efficient and simple tool to study
      functional genomics in various plants. However, previously developed VIGS vectors
      have certain limitations, owing to their inability to be used in tissue-specific
      functional study. In the present study, we developed a Chilli leaf curl virus
      (ChiLCV)-based VIGS vector for its tissue-specific utilization by replacing the
      coat protein gene (open reading frame (ORF) AV1) with the gene of interest for
      phytoene desaturase (PDS) of Nicotiana benthamiana. Functional validation of
      ChiLCV-based VIGS in N. benthamiana resulted in systemic silencing of PDS
      exclusively in the phloem region of inoculated plants. Furthermore, expression of
      enhanced green fluorescence protein (EGFP) using the same ChiLCV vector was
      verified in the phloem region of the inoculated plants. Our results also
      suggested that, during the early phase of infection, ChiLCV was associated with
      the phloem region, but at later stage of pathogenesis, it can spread into the
      adjoining non-vascular tissues. Taken together, the newly developed ChiLCV-based
      vector provides an efficient and versatile tool, which can be exploited to unveil
      the unknown functions of several phloem-specific genes.

PMID- 27878583
TI  - Imaging button battery ingestions and insertions in children: a 15-year single
      center review.
AB  - BACKGROUND: Recent studies have shown an increase in morbidity associated with
      button battery ingestions in children. OBJECTIVE: To perform a comprehensive,
      imaging-focused review of all patients with confirmed button battery
      ingestions/insertions imaged at our institution in the last 15 years. MATERIALS
      AND METHODS: Radiology reports from Jan. 1, 2000, to July 12, 2015, were searched
      for the terms "battery" and "batteries." Confirmed cases of battery
      ingestion/insertion for which images were available were reviewed. Cases were
      reviewed for imaging studies performed, imaging findings, patient demographics,
      clinical history and management. Two pediatric gastroenterologists reviewed
      endoscopic images and graded mucosal injuries in selected cases. RESULTS: Two
      hundred seventy-six cases were reviewed. All patients were imaged with
      radiography, 19 with fluoroscopy (6.8%), and 4 with CT (1.4%). Batteries retained
      in the esophagus (n = 27, 9.8%) were larger in diameter on average than those
      that had passed distally (22.1 +/- 3.3 mm vs. 13.7 +/- 1.6 mm, P<0.0001). Battery
      diameter >=20 mm was associated with esophageal impaction (P<0.0001) and higher
      grade esophageal injury (P<0.0001). Mean battery diameter was greater for
      patients with grade 1 or higher mucosal injury than for patients with no mucosal
      injury (22.1 +/- 2.1 mm vs. 14.7 +/- 4.5 mm, P<0.0001). Sixteen percent (4/25) of
      patients with grade >=1 esophageal injury had batteries in the stomach on initial
      imaging. Five patients (1.8%) had serious clinical complications (e.g.,
      esophageal perforation, tracheoesophageal fistula). CONCLUSION: Button batteries
      >20mm in diameter warrant increased clinical scrutiny due to higher likelihood
      and severity of injury. Implementation of recent pediatric gastroenterology
      societal guidelines will likely lead to a substantial increase in the number of
      CT and MRI examinations.

PMID- 27878584
TI  - Altered intrinsic brain activity after chemotherapy in patients with gastric
      cancer: A preliminary study.
AB  - OBJECTIVES: To characterize the pattern of altered intrinsic brain activity in
      gastric cancer patients after chemotherapy (CTx). METHODS: Patients before and
      after CTx (n = 14) and control subjects (n = 11) underwent resting-state
      functional MRI (rsfMRI) at baseline and 3 months after CTx. Regional homogeneity
      (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF
      (fALFF) were calculated and compared between the groups using the two-sample t
      test. Correlation analysis was also performed between rsfMRI values (i.e., ReHo,
      ALFF, and fALFF) and neuropsychological test results. RESULTS: Patients showed
      poor performance in verbal memory and executive function and decreased rsfMRI
      values in the frontal areas even before CTx and showed decreased
      attention/working memory and executive function after CTx compared to the control
      subjects. In direct comparison of values before and after CTx, there were no
      significant differences in neuropsychological test scores, but decreased rsfMRI
      values were observed at the frontal lobes and right cerebellar region. Among
      rsfMRI values, lower ALFF in the left inferior frontal gyrus was significantly
      associated with poor performance of the executive function test. CONCLUSIONS: We
      observed decreased attention/working memory and executive function that
      corresponded to the decline of frontal region activation in gastric cancer
      patients who underwent CTx. KEY POINTS: * Intrinsic brain activity of gastric
      cancer patients after chemotherapy was described. * Brain activity and
      neuropsychological test results were correlated. * Working memory and executive
      function decreased after chemotherapy. * Decreased cognitive function
      corresponded to decreased activation of the frontal region.

PMID- 27878587
TI  - Reply to the letter 'Linguistic validation of the "FACE-Q Rhinoplasty Module" in
      Italian'.

PMID- 27878586
TI  - [Parainfectious optic neuritis with macular infiltrate in Neisseria meningitidis
      B meningitis].
AB  - OBJECTIVE: We report on the case of a young immunocompetent female patient with
      parainfectious optic neuritis and macular inflitrate due to Neisseria
      meningitidis B meningitis. METHOD: Case report RESULTS: A 22-year-old female
      patient was admitted to the emergency department for intensive care treatment
      with a strong suspicion of meningitis. Clinical and serological parameters were
      indicative of a bacterial genesis of the meningitis. By analysis of the
      cerebrospinal fluid (CSF) Neisseria meningitidis type B could be detected.
      Subjective and objective symptoms could be improved by immediate intravenous
      administration of antibiotics; however, 1 day before discharge the patient
      complained of a sudden left-sided, painful loss of vision with extreme
      photophobia. The ophthalmoscopic examination revealed profound ciliary injection
      with slight anterior uveitis and papilledema with macular infiltration and
      diffuse petechiae-like retinal hemorrhage. After exclusion of viral proliferation
      in the CSF systemic steroid therapy was carried out together with continuation of
      antibiotic therapy and the eye was treated with local steroids and mydriatics.
      This resulted in healing of the ocular inflammation and partial recovery of
      vision. CONCLUSION: The painful loss of vision in this patient is probably due to
      parainfectious optic neuritis with macular infiltrate from Neisseria meningitidis
      B meningitis, which is an unusual course. Despite the rarity of this disease the
      complication of a parainfectious inflammation of the optic nerve should be
      considered and appropriate steps taken when the corresponding symptoms occur.

PMID- 27878562
TI  - Full-dose Perindopril/Indapamide in the Treatment of Difficult-to-Control
      Hypertension: The FORTISSIMO Study.
AB  - BACKGROUND AND OBJECTIVE: Blood pressure (BP) control in hypertensive patients
      remains poor worldwide, particularly in high-risk patients with hypertension and
      diabetes. Guidelines recommend that such patients receive prompt pharmacological
      therapy at maximal doses to rapidly control BP. We aimed to evaluate efficacy and
      safety of single-pill combination (SPC) perindopril/indapamide (PER/IND) at full
      dose (10/2.5 mg) in hypertensive patients, including diabetics, with BP
      uncontrolled by previous medication. METHODS: Twelve-week prospective,
      observational study in patients with uncontrolled hypertension (>=160-200 mmHg
      systolic BP [SBP] and <110 mmHg diastolic BP [DBP]) on a previous SPC or free
      dose combination of renin-angiotensin system blocker plus thiazide diuretic,
      substituted with PER/IND 10/2.5 mg. Office BP, quality of life, and blood
      parameters were evaluated in the whole cohort and patients with type 2 diabetes
      mellitus. RESULTS: 2120 ambulatory hypertensive patients were enrolled, including
      307 with type 2 diabetes. Two weeks after substitution, SBP significantly
      decreased from 171.0 +/- 13.3 to 148.6 +/- 13.4 mmHg, and DBP from 98.6 +/- 8.3
      to 88.8 +/- 7.9 mmHg (both p < 0.00001). A similar rapid decrease was noted in
      the diabetes subgroup. After 12 weeks, BP had reduced by 42/19 mmHg in the whole
      cohort (diabetes subgroup: 41/18 mmHg). Most (84%; diabetes subgroup: 77%)
      patients reached BP target (<140/90 mmHg). Laboratory tests and quality of life
      improved in the whole cohort and the diabetic subgroup. CONCLUSIONS: Switching to
      PER/IND at full dose (10/2.5 mg) was well tolerated, leading to fast BP reduction
      and control in the majority of patients with uncontrolled hypertension, including
      difficult-to-treat patients with diabetes.

PMID- 27878585
TI  - Motion and emotion: anxiety-axial connections in Parkinson's disease.
AB  - Anxiety is a serious and frequent complication in Parkinson's disease (PD) that
      significantly affects the quality of life of patients. Multiple neuroanatomical,
      experimental, and clinical studies suggest its close association with axial
      disturbances. However, whether this relation applies for PD patients (commonly
      suffering from axial difficulties, such as balance and gait disturbance) has not
      been properly tested yet. The purpose of this study was to determine whether PD
      patients suffering from axial symptoms have higher levels of anxiety than others
      and to identify other factors associated with anxiety-axial connections. In this
      questionnaire study, 212 patients with PD were assessed by standardized scales,
      such as Hamilton Anxiety Scale, Montgomery-Asberg Depression Rating Scale,
      Montreal Cognitive Assessment, examining their mood and cognitive status. These
      data were correlated to dominant motor symptoms of these patients, such as
      tremor, rigidity, bradykinesia, and axial symptoms. Unlike other motor symptoms,
      only axial symptoms showed to be significantly related to higher levels of
      anxiety. The patients suffering from anxiety and axial problems have also shown
      significantly higher depression levels. Axial disturbances are related to higher
      anxiety levels in PD patients. It is crucial to pay high attention to symptoms of
      anxiety in patients having postural instability or gait disorder. Further
      clinical studies are desirable to investigate new, practical implications of
      anxiety-axial connection to provide complex management options of these serious
      symptoms.

PMID- 27878588
TI  - The impact of erdosteine on cisplatin-induced ototoxicity: a proteomics approach.
AB  - Cisplatin is a commonly used chemotherapeutic agent and causes serious side
      effects, including progressive and irreversible hearing loss. No treatment is
      currently available for cisplatin-induced ototoxicity. We have previously
      demonstrated that erdosteine, a potent antioxidant, partially protected the
      cochlea against cisplatin toxicity in vivo. The aims of this study were to (1)
      evaluate the protein profiles of the cochlea following cisplatin administration
      and (2) evaluate the impact of erdosteine on the protein profile using a
      proteomics-based approach. Thirty Sprague-Dawley rats were injected
      intraperitoneally with saline (n = 10), cisplatin (n = 10) or with cisplatin and
      erdosteine (n = 10). The cisplatin dosage was 14 mg/kg and for erdosteine, 500
      mg/kg. Following euthanasia, protein lysates were obtained from fresh-frozen
      cochleae and were processed for mass spectrometry and western blotting. We
      detected 445 proteins that exhibited a twofold change or greater in the cisplatin
      group as compared to the control group. Of these, 18 proteins showed a fourfold
      or greater change in expression associated with cisplatin administration,
      including ras-related protein Rab-2A, Rab-6A, cd81, ribosomal protein S5, and
      myelin basic protein, which were downregulated, while Ba1-647 and fibrinogen
      (alpha chain), amongst others, were upregulated. Co-administration of erdosteine
      revealed a reversal of these changes in the expression of ras-related protein Rab
      2A, ribosomal protein S5, myelin basic protein, and fibrinogen (alpha chain);
      erdosteine also upregulated glutathione reductase. In this study, we identified
      various proteins that may play a role in cisplatin-induced ototoxicity. We also
      observed the changes resulting from co-treatment with an antioxidant.

PMID- 27878589
TI  - Chronological changes in microbial profiles in external and middle ear diseases:
      a 20-year study in Korea.
AB  - Microbial infection is one of the most significant causes of ear diseases, but
      microbial profiles are very diverse according to the diseases and change over
      time. The purpose of the study was to clarify differences and chronological
      changes in causative pathogens among infectious ear diseases over the last 20
      years, and to identify antibiotic resistance. In total, 1191 isolates were
      included from patients diagnosed with chronic otitis media without cholesteatoma
      (COM), cholesteatomatous otitis media (Chole), middle ear effusion (MEE),
      including acute otitis media and otitis media with effusion, and external otitis
      (EO). Data were collected periodically for the years 1995, 2000, 2004, 2009, and
      2013. Culture results and antibiotic resistance were assessed. The most common
      microorganism identified was S. aureus. The microbial profiles differed
      significant among the COM, Chole, and MEE groups (p < 0.001). In contrast, there
      was no distinct difference between COM and EO (p = 0.332). COM, Chole, and MEE
      also showed significant chronological changes in microbial profiles over time.
      The frequency of CNS increased markedly in COM and Chole (p = 0.029 and 0.028,
      respectively); however, S. pneumoniae infection decreased significantly in MEE (p
      = 0.016). Methicillin-resistant S. aureus (MRSA) demonstrated a constant trend (p
      = 0.564), whereas ciprofloxacin-resistant P. aeruginosa increased over time (p <
      0.001). Microbial profiles have changed over a 20-year period. Increases in the
      frequency of coagulase-negative Staphylococcus (CNS) and bacterial resistance to
      ciprofloxacin, used widely in treating ear infections, are noteworthy.

PMID- 27878590
TI  - Use of saline waste water from demineralization of cheese whey for cultivation of
      Schizochytrium limacinum PA-968 and Japonochytrium marinum AN-4.
AB  - Saline waste water from demineralization of cheese whey was used as the main
      component of waste saline medium (WSM) for cultivation of thraustochytrids. The
      suitability of WSM for cultivation of Schizochytrium limacinum PA-968 and
      Japonochytrium marinum AN-4 was evaluated by comparison with cultivation on
      nutrient medium (NM) in shake flask and fermenter cultures. Biomass
      productivities achieved in WSM for the thraustochytrids were comparable with
      those in NM for both shake flask and fermenter cultures. The maximum total lipid
      content (56.71% dry cell weight) and docosahexaenoic acid productivity (0.86
      g/L/day) were achieved by J. marinum AN-4 grown on WSM in shake flask and
      fermenter cultures, respectively. A cost estimate of WSM suggests that this
      medium could result in lower production costs for thraustochytrid biomass and
      lipids and contribute to the effective reduction in saline diary process waste
      water.

PMID- 27878591
TI  - Sugaring-out extraction of acetoin from fermentation broth by coupling with
      fermentation.
AB  - Acetoin is a natural flavor and an important bio-based chemical which could be
      separated from fermentation broth by solvent extraction, salting-out extraction
      or recovered in the form of derivatives. In this work, a novel method named as
      sugaring-out extraction coupled with fermentation was tried in the acetoin
      production by Bacillus subtilis DL01. The effects of six solvents on bacterial
      growth and the distribution of acetoin and glucose in different solvent-glucose
      systems were explored. The operation parameters such as standing time, glucose
      concentration, and volume ratio of ethyl acetate to fermentation broth were
      determined. In a system composed of fermentation broth, glucose (100%, m/v) and
      two-fold volume of ethyl acetate, nearly 100% glucose was distributed into bottom
      phase, and 61.2% acetoin into top phase without coloring matters and organic
      acids. The top phase was treated by vacuum distillation to remove solvent and
      purify acetoin, while the bottom phase was used as carbon source to produce
      acetoin in the next batch of fermentation.

PMID- 27878592
TI  - High-frequency aflibercept injections in persistent neovascular age-related
      macular degeneration.
AB  - PURPOSE: To report the 1-year outcomes of every-4-weeks (Q4W) as-needed
      aflibercept treatment in resistant neovascular age-related macular degeneration
      (nAMD) patients who had been treated and failed prior bevacizumab or ranibizumab
      injections, and who also responded poorly to every-8-weeks (Q8W) aflibercept
      treatment. METHODS: Forty-three eyes of 39 patients with persistent nAMD despite
      monthly bevacizumab and/or ranibizumab injections and who were switched to Q8W 2
      mg aflibercept injections, but showed persistence of fluid were included.
      Patients were treated with as-needed Q4W aflibercept injections with monthly
      monitoring. Maximum retinal thickness (MRT), central macular thickness (CMT),
      maximum pigment epithelial detachment height (PED) and best-corrected visual
      acuity (BCVA) were assessed and compared to baseline when high-frequency
      aflibercept was initiated. RESULTS: A mean of 8 (interquartile range, 4-11) Q4W
      injections were given during the follow-up. MRT and CMT significantly decreased
      at all follow-up visits (p < 0.05); however, there was no significant change in
      maximum PED height (p > 0.05) at any visit. Mean BCVA was 0.38 +/- 0.28 (logMAR)
      (~20/63, Snellen) at baseline, and 0.4 +/- 0.34 (logMAR) (~20/76, Snellen) at 1
      year (p = 0.76). Seventy-two percent of eyes maintained a final BCVA of 20/63 or
      better. Twelve eyes (28 %) had some subretinal scar tissue formation and 5 eyes
      (11.6 %) had evidence of atrophy at 1 year. CONCLUSION: A stepwise algorithm with
      Q4W as-needed aflibercept treatment led to anatomic improvement in previously
      treated eyes which failed other therapies, including aflibercept every 8 weeks.
      Lack of visual improvement may be due to a ceiling effect as our eyes generally
      had good visual acuity.

PMID- 27878593
TI  - Re-evaluation of liver transaminase cutoff for CT after pediatric blunt abdominal
      trauma.
AB  - PURPOSE: Current guidelines for computed tomography (CT) after blunt trauma were
      developed to capture all intra-abdominal injuries (IAI). We hypothesize that
      current AST/ALT guidelines are too low leading to unnecessary CT scans for
      children after blunt abdominal trauma (BAT). METHODS: Patients who received CT of
      the abdomen after blunt trauma at our Level I Pediatric Trauma Center were
      stratified into a high risk (HR) (liver/spleen/kidney grade >=III, hollow
      viscous, or pancreatic injuries) and low risk (LR) (liver/kidney/spleen injuries
      grade <=II, or no IAI) groups. RESULTS: 247 patients were included. Of the 18
      patients in the HR group, two required surgery (splenectomy and sigmoidectomy).
      Transfusion was required in 30% of grade III and 50% of grade IV injuries. Eleven
      (5%) patients in LR group were transfused for indications other than IAI, and
      none were explored surgically. Both AST (r = 0.44, p < 0.001) and ALT (r = 0.43,
      p < 0.001) correlated with grade of liver injury. Using an increased threshold of
      AST/ALT, 400/200 had a negative predictive value of 96% in predicting the
      presence of HR liver injuries. CONCLUSION: The current cutoff of liver enzymes
      leads to over-identification of LR injuries. Consideration should be given to an
      approach that aims to utilize CT in pediatric BAT that identifies clinically HR
      injury.

PMID- 27878594
TI  - Healthy brain ageing assessed with 18F-FDG PET and age-dependent recovery factors
      after partial volume effect correction.

PMID- 27878595
TI  - Cell-type-specific expression of NFIX in the developing and adult cerebellum.
AB  - Transcription factors from the nuclear factor one (NFI) family have been shown to
      play a central role in regulating neural progenitor cell differentiation within
      the embryonic and post-natal brain. NFIA and NFIB, for instance, promote the
      differentiation and functional maturation of granule neurons within the
      cerebellum. Mice lacking Nfix exhibit delays in the development of neuronal and
      glial lineages within the cerebellum, but the cell-type-specific expression of
      this transcription factor remains undefined. Here, we examined the expression of
      NFIX, together with various cell-type-specific markers, within the developing and
      adult cerebellum using both chromogenic immunohistochemistry and co
      immunofluorescence labelling and confocal microscopy. In embryos, NFIX was
      expressed by progenitor cells within the rhombic lip and ventricular zone. After
      birth, progenitor cells within the external granule layer, as well as migrating
      and mature granule neurons, expressed NFIX. Within the adult cerebellum, NFIX
      displayed a broad expression profile, and was evident within granule cells,
      Bergmann glia, and interneurons, but not within Purkinje neurons. Furthermore,
      transcriptomic profiling of cerebellar granule neuron progenitor cells showed
      that multiple splice variants of Nfix are expressed within this germinal zone of
      the post-natal brain. Collectively, these data suggest that NFIX plays a role in
      regulating progenitor cell biology within the embryonic and post-natal
      cerebellum, as well as an ongoing role within multiple neuronal and glial
      populations within the adult cerebellum.

PMID- 27878596
TI  - Brief report on academic contributions from China on the topic of rheumatic
      diseases.
AB  - Academic contributions by Chinese scholars have grown to take second place
      worldwide since 2009. However, little was known about Chinese academic
      contributions and their influence on rheumatic diseases. In order to present an
      overview of this field, a comprehensive bibliometrics analysis was performed
      based on data from two databases up to 2015. Since 2013, China has occupied third
      place regarding the number of rheumatic diseases' publications. Nevertheless,
      most of these articles were not associated with high impact factors or frequent
      citations, let alone great influence. Multidisciplinary teams are being formed.
      Although on the right track, more efforts in all aspects are needed to improve
      developments in the area of rheumatology in China.

PMID- 27878597
TI  - The sweet cherry (Prunus avium) FLOWERING LOCUS T gene is expressed during floral
      bud determination and can promote flowering in a winter-annual Arabidopsis
      accession.
AB  - KEY MESSAGE: FT gene is expressed in leaves and buds and is involved in floral
      meristem determination and bud development in sweet cherry. In woody fruit
      perennial trees, floral determination, dormancy and bloom, depends on perception
      of different environmental and endogenous cues which converge to a systemic
      signaling gene known as FLOWERING LOCUS T (FT). In long-day flowering plants, FT
      is expressed in the leaves on long days. The protein travels through the phloem
      to the shoot apical meristem, where it induces flower determination. In perennial
      plants, meristem determination and flowering are separated by a dormancy period.
      Meristem determination takes place in summer, but flowering occurs only after a
      dormancy period and cold accumulation during winter. The roles of FT are not
      completely clear in meristem determination, dormancy release, and flowering in
      perennial plants. We cloned FT from sweet cherry (Prunus avium) and analyzed its
      expression pattern in leaves and floral buds during spring and summer.
      Phylogenetic analysis shows high identity of the FT cloned sequence with
      orthologous genes from other Rosaceae species. Our results show that FT is
      expressed in both leaves and floral buds and increases when the daylight reached
      12 h. The peak in FT expression was coincident with floral meristem identity
      genes expression and morphological changes typical of floral meristem
      determination. The Edi-0 Arabidopsis ecotype, which requires vernalization to
      flower, was transformed with a construct for overexpression of PavFT. These
      transgenic plants showed an early-flowering phenotype without cold treatment. Our
      results suggest that FT is involved in floral meristem determination and bud
      development in sweet cherry. Moreover, we show that FT is expressed in both
      leaves and floral buds in this species, in contrast to annual plants.

PMID- 27878599
TI  - [Acoustic reflexes of children with and without central auditory processing
      disorders].
AB  - BACKGROUND: According to international standards, determination of acoustic
      reflex thresholds (ART) is one of the established objective measurements in the
      diagnostic workup of central auditory processing disorders (CAPD). However, there
      is still no evidence for the significance of ART in CAPD diagnosis. PATIENTS AND
      METHODS: This study tested 57 children with proven CAPD and 50 healthy children
      (control group) with regard to group differences in mean ART (sine tones or
      bandpass-filtered noise). Additionally, it was investigated whether there were
      group differences between the mean dissociations of ART for sine tones or
      bandpass filtered noise. RESULTS: Neither ipsi- nor contralaterally were
      significant clinically relevant group differences (p < 0.050) between the mean
      ART of children with and without CAPD found. After Bonferroni correction, a
      significant group difference in the percentage of non-triggered reflexes was only
      observed with left-sided contralateral 2 kHz stimuli. Concerning the number of
      dissociations >=20 dB, no significant group differences (p < 0.050) were detected
      either ipsi- or contralaterally (Fisher's test). CONCLUSION: The results of the
      study seem to indicate no clinically relevant ability of ART measurements to
      distinguish between children with and without CAPD. This renders the benefit of
      ART measurements for CAPD diagnosis questionable.

PMID- 27878598
TI  - Implementing the Free Water Protocol does not Result in Aspiration Pneumonia in
      Carefully Selected Patients with Dysphagia: A Systematic Review.
AB  - The Frazier Free Water Protocol was developed with the aim of providing patients
      with dysphagia an option to consume thin (i.e. unthickened) water in-between
      mealtimes. A systematic review was conducted of research published in peer
      reviewed journals. An electronic search of the EMBASE, CINAHL and MEDLINE
      databases was completed up to July 2016. A total of 8 studies were identified for
      inclusion: 5 randomised controlled trials, 2 cohort studies with matched cases
      and 1 single group pre-post intervention prospective study. A total of 215
      rehabilitation inpatients and 30 acute patients with oropharyngeal dysphagia who
      required thickened fluids or were to remain 'nil by mouth', as determined by
      bedside swallow assessment and/or videofluoroscopy/fiberoptic endoscopic
      evaluation of swallowing, were included. Meta-analyses of the data from the
      rehabilitation studies revealed (1) low-quality evidence that implementing the
      protocol did not result in increased odds of having lung complications and (2)
      low-quality evidence that fluid intake may increase. Patients' perceptions of
      swallow-related quality of life appeared to improve. This review has found that
      when the protocol is closely adhered to and patients are carefully selected using
      strict exclusion criteria, including an evaluation of their cognition and
      mobility, adult rehabilitation inpatients with dysphagia to thin fluids can be
      offered the choice of implementing the Free Water Protocol. Further research is
      required to determine if the Free Water Protocol can be implemented in settings
      other than inpatient rehabilitation.

PMID- 27878600
TI  - Narrow band imaging for early diagnosis of epithelial dysplasia and microinvasive
      tumors in the upper aerodigestive tract.
AB  - The various stages of tumor growth are characterized by typical epithelial,
      vascular, and secondary connective tissue changes. Narrow Band Imaging (NBI)
      endoscopy is a minimally invasive imaging technique that presents vascular
      structures in particular at a higher contrast than white light endoscopy alone.
      In combination with high-resolution image recording and reproduction (high
      definition television, HDTV; ultra-high definition, 4K), progress has been made
      in otolaryngological differential diagnostics, both pre- and intraoperatively.
      This progress represents an important step toward a so-called optical biopsy.
      Flexible endoscopy in combination with NBI allows for a detailed assessment of
      areas of the upper aerodigestive tract that are difficult to assess by rigid
      endoscopy. Papillomas along with precancerous and cancerous lesions are
      characterized by epithelial and connective tissue changes as well as by typical
      perpendicular vascular changes. Systematic use of NBI is recommended in the
      differential diagnosis of malignant lesions of the upper aerodigestive tract. NBI
      also offers a significant improvement in the pre- and intraoperative assessment
      of superficial resection margins. In particular, the combination of NBI and
      contact endoscopy (compact endoscopy) facilitates excellent therapeutic decisions
      during tumor surgery. Intraoperative determination of resection margins at an
      unprecedented precision is possible. In addition, assessment of the form and
      extent of the perpendicular vessel loops stimulated by epithelial signaling
      enables differential diagnostic decisions to be made, approximating our goal of
      an optical biopsy.

PMID- 27878602
TI  - ["He is not that important anymore" : General practitioners in a specialized
      palliative home care setting from a patient's point of view].
AB  - BACKGROUND: The outpatient medical care of palliative patients (PPs) has always
      fallen within the duties of general practitioners. Since the specialized
      palliative out-patient care (SAPV) legislation in 2007 palliative home care teams
      (PCTs) were established, providing holistic medical, nursing, and psychosocial
      support for patients with life-limiting illness and their care providers.
      OBJECTIVES: The article explores the role of GPs in palliative home care settings
      with PCTs from the patient's perspective. MATERIALS AND METHODS: From December
      2014 to January 2015 we conducted 23 qualitative, semi-structured interviews with
      severely ill patients receiving specialist palliative care at home in Germany.
      The theory-based analysis followed the qualitative content analysis according to
      Mayring. RESULTS: The expectations of PPs towards their GP in integrated
      palliative care were influenced by individual criteria such as availability,
      intensity and duration of the doctor-patient-relationship. In relation to the
      quality of the long-term relationship and more specifically for basic medical
      care GPs still play an important role. On the other hand, PCTs are becoming
      increasingly important. In addition to the pain-management and symptom control
      responsibilities, they meet the daily care needs of PPs and their caregivers by
      coordinating the care network as well as providing psychosocial support and 24/7
      care. CONCLUSIONS: Shifting of traditional tasks from GPs to PCTs influences the
      role of the GP. PCTs can unburden the GP from unrealistic expectations and
      improve the patients' quality of life. However, this leads to a tendency for
      reduced importance of the GP.

PMID- 27878604
TI  - [Paediatric palliative care (PPC) - a particular challenge : Tasks, aims and
      specifics].
AB  - In Germany, there are about 50,000 children, adolescents and young adults with
      life threatening or life limiting conditions, who will likely die due to their
      illness before reaching the age of 40. In recent years prevalence has increased
      significantly.The aim of paediatric palliative care (PPC) is to optimize quality
      of life for the child, adolescent or young adult and its whole family. Whenever
      possible the patient should be treated at home.The very complex and rare diseases
      as well as the patients' wide range of age and developmental stage are
      particularly challenging within PPC. Many PPC patients have cognitive
      disabilities and are not able to communicate verbally. In contrast to adult
      palliative care, PPC is often delivered for many years.To date, families with a
      child suffering from a life limiting condition have access to several care
      systems; however most of them are still financed by donations. One of PPC's most
      important tasks is the implementation of individual case management to find the
      right mix of care provision, its flexible adaption on changing needs and the
      appropriate intensity of care.Specific education and training courses in the
      field of PPC are still rare. There is a single chair for childrens' pain therapy
      and paediatric palliative care at Witten/Herdecke University in Germany. In
      addition, quality-checked multiprofessional PPC courses for the additional
      "palliative health care professional" designation based on the Dattelner
      Curriculum are offered at several institutions.

PMID- 27878603
TI  - [The epidemiology of varicella disease in Germany after introduction of a
      vaccination recommendation : Analysis of mandatory and sentinel data between 2002
      and 2014].
AB  - BACKGROUND: Since 2004 a single varicella vaccination for all infants aged 11-14
      months has been recommended in Germany and since 2009 a second dose at the age of
      15-23 months is recommended. Vaccination coverage after 24 months rose from 43%
      in 2006 to 87.5% in 2012. A mandatory notification system was introduced in the
      New Federal States (NFS) between 2002 and 2009 and nationwide in 2013. A national
      sentinel system has been in place since 2005. OBJECTIVE AND METHOD: We analyzed
      both data sources to describe the varicella epidemiology related to vaccination
      coverage after initiation of routine childhood varicella vaccination and to
      evaluate both notification systems regarding informative value and data quality.
      We looked at trends, age distribution and incidences using Microsoft Excel and
      Stata12. Vaccination coverage data were available from health insurance claims
      data. RESULTS: By 2013 a decrease of cases/medical practice/month from 3.47 to
      0.43 was observed. The incidence in the NFS declined from 32 to 12 out of
      100,000. Sentinel and mandatory notification data showed the largest decrease
      among the 1-4 year-olds (-94 and -90% resp.). In 2014, varicella incidences
      increased in all age groups, but not the cases/medical-practice/month by age in
      the sentinel. DISCUSSION: Increasing vaccination coverage and decreasing
      varicella cases demonstrate the success of routine childhood varicella
      vaccination. Mandatory notification data allow incidence calculation; The
      sentinel system has been providing more detailed information about vaccination
      status, better data quality and continuous national data since 2005, irrespective
      of the Infectious disease protection act. Trends and age distribution can be
      continuously calculated, whereas the nationwide mandatory data collected in the
      short period since April 2013 can only be evaluated to a limited extent.

PMID- 27878605
TI  - [Special medical problems in end-of-life care : Crisis at the end of life - Which
      therapy is adequate and when is redefining treatment goals appropriate?]
AB  - Crisis at the end of life are exceptional challenges for patients, relatives and
      therapists. With respect to the individual treatment goals and the patients'
      autonomy, therapeutic action should be commenced in an adequate manner in order
      to preserve the patients' quality of life as much as possible. Advance care
      planning for specific critical scenarios may be helpful in order to treat
      patients according to their wishes and values even if they are not capable to
      express themselves. Furthermore, a crisis plan can define the scope of action for
      therapists in emergency situations. Dyspnea, pain and delirium are symptoms that
      may often lead to emergency calls. In such cases, pharmacological and other
      treatment options are available. Options for causal therapy should be checked and
      performed if adequate. Opioids are used to relieve pain and dyspnea. In a state
      of delirium, highly potent neuroleptics and atypical antipsychotics are used. For
      the treatment of anxiety or restlessness benzodiazepines can be prescribed.
      Sedative medication may reduce stress, for instance in the case of acute
      catastrophic bleeding. Palliative sedation is an ultima ratio concept for
      refractory symptoms at the end of life. Clinical practice guidelines (such as the
      German guideline "Palliative care for patients with incurable cancer") may
      provide an overview of the evidence base on symptom-guided therapy at the end of
      life.

PMID- 27878601
TI  - Reduction of permanent hearing loss by local glucocorticoid application : Guinea
      pigs with acute acoustic trauma.
AB  - BACKGROUND: High-intensity noise exposure from impulse and blast noise events
      often leads to acute hearing loss and may cause irreversible permanent hearing
      loss as a long-term consequence. Here, a treatment regime was developed to limit
      permanent damage based on a preclinical animal model of acute noise trauma. AIM:
      To develop clinical trials for the treatment of acute noise traumas using
      approved drugs. The otoprotective potential of glucocorticoids applied locally to
      the inner ear was examined. MATERIALS AND METHODS: A series of experiments with
      different impulse noise exposures were performed. Permanent hearing loss and hair
      cell density were assessed 14 days after exposure. Hearing and hair cell
      preservation were investigated as a function of the glucocorticoid dose. RESULTS:
      After impulse noise exposure, local application to the round window of the
      cochlea of high-dose prednisolone (25 mg/ml) or methylprednisolone (12.5 mg/ml)
      resulted in a statistically significant reduction in hearing loss compared with
      the control group. CONCLUSION: The local application of high doses of the drugs
      to the round window of the cochlea appears to be an effective treatment for acute
      noise trauma.

PMID- 27878606
TI  - [Well connected - optimally cared for! : Beneficial factors of collaboration in
      hospice and palliative care networks in Bavaria].
AB  - BACKGROUND: The Bavarian State Ministry of Health and Care fosters the
      establishment of regional hospice and palliative care networks in Bavaria,
      Germany. Little is known about well-tried structures and beneficial strategies of
      collaboration within such networks. OBJECTIVES: The present study aims to
      investigate general conditions under which hospice and palliative care networks
      in Bavaria perform successfully and to explore modes of working, forms of
      organisation, and channels of communication. METHODS: Data were collected between
      March and June 2015 in semi-structured interviews with ten coordinators and
      chairpersons of ten Bavarian hospice and palliative care networks. Results of
      this status quo analysis concerning aspects of network models and beneficial
      factors of networking were discussed in a subsequent workshop. The workshop took
      place in November 2015 with eight representatives of five networks. Individual
      interviews and the discussion of the diagnostic workshop were audiotaped and
      transcribed verbatim. Data were analysed with the aid of the computer-assisted
      qualitative data analysis software MAXQDA (Software fur qualitative Datenanalyse
      (1989-2015). VERBI Software Consult Sozialforschung GmbH, Berlin, Germany).
      Hypotheses were formulated adapted from Grounded Theory. RESULTS: Networking
      factors and characteristics are quite congruent. Beneficial and diverse factors
      identified by network coordinators and moderators represent three major topics:
      network organisation and coordination, communication and information channels,
      and public visibility. CONCLUSIONS: Well-tried and established practices of
      networking are present in the hospice and palliative care networks included in
      the study. The experiences and visions of the networks will foster the
      compilation of a best practice recommendation for the establishment of new and
      the enhancement of existing networks.

PMID- 27878607
TI  - ["Are you going to die?" When children and adolescents experience the death of a
      close one].
AB  - The illness and death of someone close is a big challenge that affects
      individuals and the whole system. To understand how children, adolescents and
      young adults experience the death of a significant other, and more specifically a
      family member, it is necessary to consider aspects of developmental psychology,
      the life-cycle phase of the family and the systemic view on the burden and
      reactions from individuals and the whole system. Palliative care and in
      particular family-oriented counselling and therapy stabilizes the system. Support
      of the adult caregiver, facilitating understanding of each other even if there
      are divergent needs as well as the support of sincere communication are important
      strategies. Children and adolescents as well as their families are supported to
      find their coherent way to deal with the imminent death of a close one and to
      integrate the experience into the biography with maximum mental wellbeing.

PMID- 27878610
TI  - Celebrating 50 Years of Publication: Year in Review!

PMID- 27878609
TI  - Patterns of the utilization of prenatal diagnosis services among pregnant women,
      their satisfaction and its associated factors in Viet Nam.
AB  - OBJECTIVES: This study aimed at understanding the patterns of the utilization of
      prenatal diagnostic (PND) services among pregnant women, their satisfaction and
      its associated factors at three regional prenatal diagnostic centres in Viet Nam.
      METHODS: A cross-sectional design was used, with a consecutive sampling method to
      recruit pregnant women who used PND services at the three biggest regional PND
      services centres in Viet Nam between January and June, 2014. A total of 298
      participants, about 100 participants per centre were interviewed and included in
      data analysis. Descriptive analyses and logistic regression methods were applied
      to identify association between satisfaction of women and their socio-economic
      characteristics. RESULTS: 80% of pregnant women received counselling on PND
      services, whilst 90% received ultrasonography services; 65.4% were satisfied with
      the PND services they used. Pregnant women, who were in a lower income group and
      received counselling but did not receive ultrasonography, were more likely to
      have higher satisfaction levels of PND services. CONCLUSIONS: A process to ensure
      that every pregnant woman receives sufficient PND counselling before and after
      receiving PND testing must be given careful and thorough consideration.

PMID- 27878608
TI  - Claudins in barrier and transport function-the kidney.
AB  - Claudins are discovered to be key players in renal epithelial physiology. They
      are involved in developmental, physiological, and pathophysiological
      differentiation. In the glomerular podocytes, claudin-1 is an important
      determinant of cell junction fate. In the proximal tubule, claudin-2 plays
      important roles in paracellular salt reabsorption. In the thick ascending limb,
      claudin-14, -16, and -19 regulate the paracellular reabsorption of calcium and
      magnesium. Recessive mutations in claudin-16 or -19 cause an inherited calcium
      and magnesium losing disease. Synonymous variants in claudin-14 have been
      associated with hypercalciuric nephrolithiasis by genome-wide association studies
      (GWASs). More importantly, claudin-14 gene expression can be regulated by
      extracellular calcium levels via the calcium sensing receptor. In the distal
      tubules, claudin-4 and -8 form paracellular chloride pathway to facilitate
      electrogenic sodium reabsorption. Aldosterone, WNK4, Cap1, and KLHL3 are powerful
      regulators of claudin and the paracellular chloride permeability. The lessons
      learned on claudins from the kidney will have a broader impact on tight junction
      biology in other epithelia and endothelia.

PMID- 27878612
TI  - MUW researcher of the month November 2016.

PMID- 27878611
TI  - Determination and Evaluation of Metallothionein and Metals in Mugil cephalus
      (Mullet) from Pontal Bay, Brazil.
AB  - To assess environmental contamination, studies have been increasingly carried out
      using biomarkers to diagnose the effects of toxic metal exposure, such as
      metallothionein (MT). In this context, the aims of the present study were to
      determine Cd, Cu, Ni and Pb concentrations, by ICP-MS, in liver samples from
      Mugil cephalus from the municipality of Ilheus, located in North-Southeastern
      Brazil, in the state of Bahia, which has been increasingly suffering from
      anthropogenic pressure, and to quantify total MT in liver and gills. Among
      essential metals, copper (199.2 MUg g-1) presented concentrations approximately 7
      times higher than allowed by the World Health Organization (30 MUg g-1). Liver
      samples showed higher concentrations than gills. Metallothionein concentrations
      indicate differential contamination along the study area. The first sampling
      showed higher induction of MT synthesis overall. Differences between liver and
      gill MT concentration trends were relatively minor, which may indicate the
      adequacy of analyzing gills in an environmental monitoring context.

PMID- 27878613
TI  - Intermittent low-dose bevacizumab in hereditary hemorrhagic telangiectasia : A
      case report.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia is an inherited autosomal
      dominant disease presenting with recurrent bleeding episodes and iron deficiency
      anemia due to vascular malformations. Hereditary hemorrhagic telangiectasia is
      associated with an increased risk of stroke, gastrointestinal bleeding and
      pulmonary hypertension and life expectancy is significantly reduced. Excess
      vascular endothelial growth factor (VEGF) plays a key role in the pathophysiology
      of the disease. CASE PRESENTATION: Here we report about a male patient with
      hereditary hemorrhagic telangiectasia presenting with pulmonary and central
      nervous system involvement experiencing repetitive nosebleeds, necessitating
      frequent local cauterization and transfusion of more than 100 units of packed red
      blood cells. After initiation of temporary therapy with the anti-VEGF antibody
      bevacizumab at a dosage of 1 mg/kg body weight every 2 weeks, the nose bleeding
      episodes and the epistaxis severity score significantly decreased and long
      lasting transfusion independence was achieved. Reinitiation of low-dose
      bevacizumab after relapse again proved effective without any documented therapy
      related adverse events. In comparison to other reported anti-VEGF antibody
      protocols in hereditary hemorrhagic telangiectasia, our treatment approach proved
      to be cost-efficient. CONCLUSION: Intermittent low-dose therapy with bevacizumab
      represents an effective and cost-efficient treatment option for transfusion
      dependent patients with hereditary hemorrhagic telangiectasia.

PMID- 27878614
TI  - Associations of intracranial pressure with brain biopsy, radiological findings,
      and shunt surgery outcome in patients with suspected idiopathic normal pressure
      hydrocephalus.
AB  - BACKGROUND: It remains unclear how intracranial pressure (ICP) measures are
      associated with brain biopsies and radiological markers. Here, we aim to
      investigate associations between ICP and radiological findings, brain biopsies,
      and shunt surgery outcome in patients with suspected idiopathic normal pressure
      hydrocephalus (iNPH). METHOD: In this study, we retrospectively analyzed data
      from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of
      these patients, 71% underwent shunt surgery. The NPH registry included data on
      clinical and radiological examinations, 24-h intraventricular pressure
      monitoring, and frontal cortical biopsy. RESULTS: The mean ICP and mean ICP pulse
      wave amplitude were not associated with the shunt response. Aggregations of
      Alzheimer's disease (AD)-related proteins (amyloid-beta, hyperphosphorylated tau)
      in frontal cortical biopsies were associated with a poor shunt response (P =
      0.014). High mean ICP was associated with Evans' index (EI; P = 0.025),
      disproportional sylvian and suprasylvian subarachnoid spaces (P = 0.014), and
      focally dilated sulci (P = 0.047). Interestingly, a high pulse wave amplitude was
      associated with AD-related biopsy findings (P = 0.032), but the mean ICP was not
      associated with the brain biopsy. The ICP was not associated with medial temporal
      lobe atrophy, temporal horn widths, or white matter changes. ICP B waves were
      associated with less atrophy of the medial temporal lobe (P = 0.018) and more
      severe disproportionality between the sylvian and suprasylvian subarachnoid
      spaces (P = 0.001). CONCLUSIONS: The EI and disproportional sylvian and
      suprasylvian subarachnoid spaces were associated with mean ICP.
      Disproportionality was also associated with ICP B waves. These associations,
      although rather weak, with elevated ICP in 24-h measurements, support their value
      in iNPH diagnostics and suggest that these radiological markers are potentially
      related to the pathogenesis of iNPH. Interestingly, our results suggested that
      elevated pulse wave amplitude might be associated with brain amyloid
      accumulation.

PMID- 27878615
TI  - Results of surgery in symptomatic non-hydrocephalic pineal cysts: role of
      magnetic resonance imaging biomarkers indicative of central venous hypertension.
AB  - BACKGROUND: We have previously proposed that pineal cysts (PCs) may result in
      crowding of the pineal recess, causing symptoms due to compression of the
      internal cerebral veins and central venous hypertension. In the present study, we
      compared clinical outcome of different treatment modalities in symptomatic
      individuals with non-hydrocephalic PCs. METHODS: The study included all patients
      managed surgically for non-hydrocephalic PCs in our Department of Neurosurgery
      over a 10-year period. We applied a questionnaire to determine occurrence of
      symptoms before and after surgery, which allowed the use of a grading scale for
      symptom severity. Magnetic resonance imaging (MRI) biomarkers indicative of
      central venous hypertension were assessed before and after surgery. RESULTS:
      Relief of symptoms after surgery was most efficiently obtained by complete
      microsurgical cyst removal [n = 15; no (0/15), some (1/15) or marked (14/15)
      improvement], and to a lesser extent by microsurgical cyst fenestration [n = 6;
      no (2/6), some (4/6) or marked (0/6) improvement]. Shunt surgery was not
      successful [n = 6; no (5/6), some (1/6) or marked (0/6) improvement]. In all
      patients, the proposed MRI biomarkers gave evidence of central venous
      hypertension (PC grades 2-4). CONCLUSIONS: Microsurgical cyst removal provided
      marked symptom relief in symptomatic individuals with non-hydrocephalic PCs and
      MRI biomarkers of central venous hypertension. The hypothesis that PC-induced
      crowding of the pineal recess may compromise venous run-off and induce a central
      venous hypertension syndrome deserves further study.

PMID- 27878616
TI  - Effectiveness of vagal nerve stimulation in medication-resistant epilepsy.
      Comparison between patients with and without medication changes.
AB  - BACKGROUND: Vagal nerve stimulation (VNS) response is not immediate. A
      progressive decline in seizure frequency is usually found during a period of 12
      18 months after implantation. During this time, the patient's medication is
      usually modified, which can create doubts about whether their clinical
      improvement is due to medication changes or to VNS itself. Our goal is to compare
      two groups of patients treated with VNS, with and without changes in their
      medication. METHODS: We prospectively analyze 85 patients who were treated with
      VNS in our hospital between 2005 and 2014. In 43 patients, changes in the
      antiepileptic drugs (EAD) were not allowed during the postoperative follow-up and
      they were compared with 42 patients who were left at the option of neurologist
      make changes in medication. We analyzed the clinical situation at 18 months and
      compared the two groups. RESULTS: Overall, 54.1% of patients had a reduction in
      seizures of 50% or higher (responders). In the group with no changes in
      medication, responders reached 63%, while in the group in which changes in
      medication were allowed, 45.2% were responders. Between responders and non
      responders, there were no statistical differences in type of epilepsy, frequency,
      previous surgery, or intensity of stimulation. CONCLUSIONS: We did not find a
      statistical difference in seizure frequency reduction between patients with or
      without changes in medication during their follow-up, so changes in medication
      did not improve the outcome. Furthermore, the absence of changes in AED can help
      to optimize the parameters of the stimulator in order to improve its
      effectiveness.

PMID- 27878617
TI  - Black hairy tongue after chemotherapy for malignant brain tumors.
AB  - Black hairy tongue (BHT) developed in five patients (2.6%) among 192 patients
      undergoing chemotherapy for malignant brain tumors. Three patients with a history
      of diabetes mellitus developed BHT within 10 days after the initiation of
      chemotherapy. The other two patients suffered more than 100 days after induction
      and lymphopenia of grade 3 or worse developed for more than 20 days, which was
      not observed in the three patients with diabetes. We found that BHT could develop
      after chemotherapy for malignant brain tumors. Patients with diabetes mellitus
      presented early after chemotherapy, while patients with longstanding severe
      lymphopenia presented in late phase.

PMID- 27878618
TI  - Effective and long-term outcome following ligation of the intersphincteric
      fistula tract (LIFT) for transsphincteric fistula.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and long-term
      outcome of the ligation of the intersphincteric fistula tract (LIFT) procedure
      for transsphincteric fistula-in-ano. METHODS: A total of 43 patients that were
      treated with LIFT procedure and had a follow-up time of more than 1 year were
      included. RESULTS: The median age was 37.18 years, and 32 (74.4%) of the patients
      were male. The median follow-up time was 26.2 months (range 13-63 months). There
      were 29 (67.4%) uncomplicated transsphincteric fistulas, 10 (23.3%) horseshoe
      transsphincteric fistulas, and 4 (9.3%) multiple fistulas. Eight (18.5%) patients
      presented with dehiscence or infection at the intersphincteric wound and were
      successfully treated with either laying open (n = 5) or local application of
      silver nitrate (n = 3). The success rate, as determined from the last follow-up
      time point, was 83.7% (36/43). The mean time to complete failure was 8.6 weeks
      (range 1-28) in 7 patients. With the exception of these 7 patients, 32/36 (88.9%)
      patients had a Cleveland Clinic Florida Faecal incontinence score of 0, 3
      patients had a score of 1, and 1 had a score of 2. No significant association was
      found between laying open and incontinence in these partial failure patients.
      CONCLUSION: The LIFT procedure can be considered an effective sphincter-sparing
      procedure in the management of transsphincteric fistula with an acceptable long
      term outcome.

PMID- 27878619
TI  - An open prospective study evaluating efficacy and safety of a new medical device
      for rectal application of activated carbon in the treatment of chronic,
      uncomplicated perianal fistulas.
AB  - PURPOSE: It has been proposed that biological/chemical substances in the
      intestine might play a role in the occurrence and deterioration of perianal
      fistulas. Elimination of such unidentified factors from the lower
      gastrointestinal tract might offer a new strategy for the management of anal
      fistulas. The aim of this study was to evaluate the clinical effects on non
      Crohn's disease perianal fistula healing, and the safety and tolerability of a
      new medical device that applies high-purity, high-activity granular activated
      carbon locally into the rectum twice daily of patients with perianal fistulas
      without any concomitant medication. METHODS: An open, single-arm, prospective
      study with active treatment for 8 weeks and an optional follow-up until week 24 (
      ClinicalTrial.gov identifier NCT01462747) among patients with chronic,
      uncomplicated perianal fistulas scheduled for surgery was conducted. RESULTS: Of
      28 patients included, 10 patients (35.7%) showed complete fistula healing
      (closed, no discharge on palpation) after 8 weeks; seven of these patients,
      corresponding to 25% of the enrolled patients, remained in remission for up to 31
      weeks. At week 8, there was a statistically significant reduction in the
      discharge visual analog scale (p = 0.04), a significant improvement in the
      patient-perceived quality of life for the category of embarrassment (p = 0.002),
      and a trend toward improvement in the other assessment categories. CONCLUSIONS:
      The treatment was well tolerated, and patient acceptance was high. The results
      support the efficacy and safety of locally administered activated carbon for the
      treatment of patients with chronic uncomplicated perianal fistulas not receiving
      any other medication for fistula problems.

PMID- 27878620
TI  - The role of single-shot metronidazole in the prevention of Clostridium difficile
      infection following ileostomy reversal surgery.
AB  - PURPOSE: Symptomatic infection with Clostridium difficile is strongly linked to
      antibiotic use and rates are higher for colorectal surgery. In February 2015,
      trust policy for antibiotic prophylaxis of ileostomy reversal surgery was changed
      from three doses of metronidazole plus cefuroxime to single-dose metronidazole,
      in a bid to reduce rates of Clostridium difficile infection. METHODS: A
      retrospective cohort study was conducted at a single, large hospital trust
      between February 2014 and February 2016, before and after change in antimicrobial
      policy. Theatre data, clinical notes and pathology results were all reviewed.
      Outcome data, patient age, gender, length of operation and hospital stay were
      extracted. RESULTS: One hundred three patients underwent ileostomy reversal
      surgery between February 2014 and February 2015. All received cefuroxime together
      with metronidazole at induction of anaesthesia followed by two further post
      operative doses as operative prophylaxis. Ninety-six patients underwent ileostomy
      reversal surgery between February 2015 and February 2016. All received single
      dose metronidazole at induction as prophylaxis. Post-operative diarrhoea was
      significantly reduced in patients given single-dose metronidazole compared with
      patients managed with multiple dose, dual antibiotic therapy (32 vs 12.5%, P
      0.001). Rates of CDI were also significantly reduced in patients given single
      dose metronidazole (6.8 vs 1%, P 0.038). CONCLUSIONS: Single-dose, pre-operative
      metronidazole is effective at reducing post-operative diarrhoea and CDI in
      ileostomy reversal surgery compared with multiple-dose cefuroxime plus
      metronidazole. Metronidazole may be effective as a prophylactic antibiotic
      against CDI in colonic surgery.

PMID- 27878621
TI  - Clinical and functional results of laparoscopic intersphincteric resection for
      ultralow rectal cancer: is there a distinction between the three types of hand
      sewn colo-anal anastomosis?
AB  - PURPOSE: The purpose of this study is to compare the clinical and functional
      outcomes of three types of hand-sewn colo-anal anastomosis (CAA) after
      laparoscopic intersphincteric resection (Lap-ISR) for patients with ultralow
      rectal cancer. METHODS: A total of 79 consecutive patients treated by Lap-ISR for
      low-lying rectal cancer in an academic medical center from June 2011 to February
      2016. According to the distal tumor margin and individualized anal length, the
      patients underwent three types of hand-sewn CAA including partial-ISR, subtotal
      ISR, and total-ISR. RESULTS: Of the 79 patients, 35.4% required partial-ISR, 43%
      adopted subtotal-ISR, and 21.5% underwent total-ISR. R0 resection was achieved in
      78 patients (98.7%). In addition to distal resection margin, there were no
      significant differences in clinicopathological parameters and postoperative
      complications between the three groups. The type of hand-sewn CAA did not
      influence the 3-year disease-free survival (DFS) or local relapse-free survival
      (LFS). At 24-months follow-up, in spite of higher incontinence scores in total
      ISR group, there were not statistically significant differences in functional
      outcomes including Wexner score or Kirwan grade between the groups. Nevertheless,
      patients with chronic anastomotic stricture showed worse anal function than those
      without the complication. CONCLUSION: The type of hand-sewn CAA after Lap-ISR may
      not influence oncological and functional outcomes, but chronic stricture
      deteriorates continence status.

PMID- 27878622
TI  - Effects of febuxostat on insulin resistance and expression of high-sensitivity C
      reactive protein in patients with primary gout.
AB  - We aimed to investigate the effects of febuxostat on IR and the expression of
      high-sensitivity C-reactive protein (hs-CRP) in patients with primary gout. Forty
      two cases of primary gout patients without uric acid-lowering therapy were
      included in this study. After a physical examination, 20 age- and sex-matched
      patients were included as normal controls. The levels of fasting insulin (INS),
      fasting blood glucose (FBG), and hs-CRP were determined. IR was assessed using
      the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Gout patients
      had higher levels of UA, INS, HOMA-IR, and hs-CRP than normal controls (P <
      0.05). After 4-, 12-, and 24-week febuxostat treatments, UA and hs-CRP
      concentrations were significantly lower than baseline (P < 0.05). INS and HOM-IR
      decreased slightly after a 4-week treatment with febuxostat but declined
      significantly after 12 and 24 weeks of treatment. Importantly, hs-CRP values
      positively correlated with those of HOMA-IR (r = 0.353, P = 0.018) and INS (r =
      0.426, P = 0.034). Our findings confirm that IR exists in gout patients and
      implicate that febuxostat can effectively control the level of serum UA and
      increase insulin sensitivity in primary gout patients.

PMID- 27878623
TI  - History of internal fixation (part 1): early developments with wires and plates
      before World War II.
AB  - Though the date at which an orthopaedic implant was first used cannot be
      ascertained with any certainty, the fixation of bone fracture using an iron wire
      was reported for the first time in a French manuscript in 1775. The first
      techniques of operative fracture treatment were developed at the end of the 18th
      and in the beginning of the 19th centuries. The use of cerclage wires to fix
      fractures was the most frequent fixation at this time. The French Berenger-Feraud
      (1832-1900) had written the first book on internal fixation. However internal
      fixation of fractures could not become a practical method before Lister had
      ensured the safety of open reduction and internal fixation in the treatment of
      fractures. Lister is not only the father of asepsis; he also used metal wires to
      fix even closed fractures. The first internal fixation by means of a plate and
      screws was described by Carl Hansmann in 1858 in Hamburg. Nevertheless, Arbuthnot
      Lane (1892) and Albin Lambotte (1905) are considered to be the founders of this
      method, which was further developed by Sherman in the first part of the 20th
      century.

PMID- 27878624
TI  - The CreB deubiquitinating enzyme does not directly target the CreA repressor
      protein in Aspergillus nidulans.
AB  - Ubiquitination/deubiquitination pathways are now recognized as key components of
      gene regulatory mechanisms in eukaryotes. The major transcriptional repressor for
      carbon catabolite repression in Aspergillus nidulans is CreA, and mutational
      analysis led to the suggestion that a regulatory ubiquitination/deubiquitination
      pathway is involved. A key unanswered question is if and how this pathway,
      comprising CreB (deubiquitinating enzyme) and HulA (ubiquitin ligase) and other
      proteins, is involved in the regulatory mechanism. Previously, missense alleles
      of creA and creB were analysed for genetic interactions, and here we extended
      this to complete loss-of-function alleles of creA and creB, and compared
      morphological and biochemical phenotypes, which confirmed genetic interaction
      between the genes. We investigated whether CreA, or a protein in a complex with
      it, is a direct target of the CreB deubiquitination enzyme, using co
      purifications of CreA and CreB, first using strains that overexpress the proteins
      and then using strains that express the proteins from their native promoters. The
      Phos-tag system was used to show that CreA is a phosphorylated protein, but no
      ubiquitination was detected using anti-ubiquitin antibodies and Western analysis.
      These findings were confirmed using mass spectrometry, which confirmed that CreA
      was differentially phosphorylated but not ubiquitinated. Thus, CreA is not a
      direct target of CreB, and nor are proteins that form part of a stable complex
      with CreA a target of CreB. These results open up new questions regarding the
      molecular mechanism of CreA repressing activity, and how the ubiquitination
      pathway involving CreB interacts with this regulatory network.

PMID- 27878625
TI  - Reference Ranges of Fetal Cardiac Biometric Parameters Using Three-Dimensional
      Ultrasound with Spatiotemporal Image Correlation M Mode and Their Applicability
      in Congenital Heart Diseases.
AB  - To determine reference values for fetal heart biometric parameters using the
      spatiotemporal image correlation (STIC) M mode and their applicability in
      congenital heart diseases (CHDs). A cross-sectional prospective study was
      conducted with 300 singleton pregnancies between 20 and 33 + 6 weeks of
      gestation. Right ventricular wall thickness (RVWT), interventricular septum
      thickness (IVST), and left ventricular wall thickness (LVWT) were measured off
      line using the STIC-M mode with the cursor perpendicular to the interventricular
      septum. Polynomial regressions adjusted with the coefficient of determination (R
      2) were performed. The curves were applied to 14 fetuses with structural CHD. For
      the reproducibility calculations, the concordance correlation coefficient (CCC)
      was used. The mean RVWT, IVST, and LVWT were 0.34 +/- 0.09 cm, 0.28 +/- 0.09 cm,
      and 0.30 +/- 0.07 cm, respectively. There was correlation between RVWT, IVST, and
      LVWT and gestational age (GA): RVWT = -0.002 + 0.013 * GA (R 2 = 0.33), IVST = 
      0.011 + 0.011 * GA (R 2 = 0.25), and LVWT = 0.056 + 0.009 * GA (R 2 = 0.26).
      RVWT, IVST, and LVWT were altered (<5th or >95th percentile) in 5/14, 5/14, and
      7/14 of the fetuses with CHD, respectively. For RVWT, IVST, and LVWT, intra
      observer (CCC = 0.86, 0.85, and 0.87, respectively) and inter-observer (CCC =
      0.86, 0.86, and 0.86, respectively) reproducibility were good/moderate. The
      reference ranges determined for fetal heart biometric parameters using STIC-M had
      good intra- and inter-observer reproducibility and were applicable to fetuses
      with CHD.

PMID- 27878627
TI  - Right Ventricular Dysfunction as an Echocardiographic Measure of Acute Rejection
      Following Heart Transplantation in Children.
AB  - Noninvasive biomarkers of acute allograft rejection (AAR) following orthotopic
      heart transplantation (OHT) are needed. The aim of this study was to investigate
      the accuracy of echocardiographic (ECHO) right ventricular (RV) global functional
      and resistance indices in the detection of AAR. This retrospective chart review
      included children with biopsy-proven AAR (grade >= 2R cellular or CD4 + antibody
      mediated rejection) following OHT and an ECHO within 12 h of the biopsy. ECHO
      measures: (a) ratio of systolic to diastolic duration (S/D), (b) RV myocardial
      performance index (MPI) and (c) tricuspid regurgitant gradient to RV outflow
      tract velocity time integral ratio (TRG/VTI), were derived at baseline, during
      AAR and at two follow-ups. Sixteen patients [56% male, mean (SD) age at OHT 3.5
      (4.3) years] had 16 AAR episodes. S/D (1.15 vs. 1.60, p < 0.01), RV MPI (0.19 vs.
      0.39, p < 0.01) and TRG/VTI (1.05 vs. 1.7, p = 0.01) deteriorated during AAR and,
      except for diastolic duration, improved significantly at first follow-up. The
      negative predictive values for S/D, RV MPI and TRG/VTI at cutoffs of 1.3, 0.31
      and 1.3 were 97, 97 and 87%, respectively. RV S/D, MPI and TRG/VTI deteriorated
      during AAR. Their excellent negative predictive values suggest that their
      incorporation in surveillance may obviate the need for routine biopsies.

PMID- 27878626
TI  - Reducing Fluoroscopic Radiation Exposure During Endomyocardial Biopsy in
      Pediatric Transplant Recipients.
AB  - Endomyocardial biopsy (EMB) with fluoroscopy is used for rejection surveillance
      in pediatric heart transplantation. Lowering frame rate may reduce radiation, but
      decreases temporal resolution and image quality. We undertook a quality
      initiative reducing frame rate from 10 frames per second (FPS) to 5 FPS. To
      assess whether lowering frame rate can reduce radiation exposure without
      compromising safety, data on EMBs from 9/2009 to 4/2013 without angiography or
      intervention were reviewed. Effective dose was calculated from dose area product
      (DAP) and fluoroscopy time. Complications were reviewed. Independent t test
      compared pre- and post-data and a general linear model were used to control for
      confounders. Paired t test of most proximate data was used for pts with EMB
      before and after our change. Eighty-six patients had 543 EMB. After adjusting for
      weight, attending, and presence of a fellow, the lower FPS group had a 60.3%
      reduction in DAP (p < 0.0001) and 53.8% drop in effective dose (p < 0.0001).
      Fluoroscopy time did not differ. Twenty-eight pts had EMBs both before and after
      the FPS change. Pair-wise analysis of this group demonstrated a 33% reduction in
      DAP (p < 0.05) and 37% drop in effective dose (p < 0.01), without difference in
      fluoroscopy time. No patient had an increase in TR > 1 grade by ECHO. There were
      no deaths or perforations. Lowering the frame rate reduces radiation exposure by
      >50% without compromising safety. Efforts to further minimize radiation exposure
      of this vulnerable population should be considered.

PMID- 27878628
TI  - Global Deformation Parameters Response to Exercise in Adolescents with Repaired
      Tetralogy of Fallot.
AB  - Exercise stress echocardiography is rarely used in the follow-up of children with
      congenital heart disease following surgical repair. There are no data on global
      longitudinal strain (GLS) and global circumferential strain (GCS) during exercise
      in adolescents with repaired tetralogy of Fallot (TOF). The purpose of this
      prospective study was to investigate GLS and GCS using speckle tracking two
      dimensional echocardiography (2D-STE) at rest and during exercise in adolescents
      with repaired TOF. Twenty patients with repaired TOF and 20 controls were
      included. The subjects exercised on a semi-supine cycle ergometer using a two
      staged 3-min step protocol of 20-40 W at 60-75 rpm. Exercise images with 2D-STE
      measurements were available for all 40 subjects. In the study group, the GLS
      values changed significantly between the baseline and third and sixth minute of
      exercise (-18.10 +/- 2.20, -16.23 +/- 4.47, -14.22 +/- 2.63, respectively, p <
      001). GCS did not vary significantly from baseline to end of the exercise testing
      (-17.49 +/- 5.14, -17.15 +/- 9.20, -15.66 +/- 3.59, respectively, p > 0.05).
      There was a statistically significant difference between the Stage I longitudinal
      strain values of the study and control groups (-14.26 +/- 9.13 and -20.22 +/-
      2.88, respectively, p = 0.02) but no significant difference between the Stage II
      values of these groups (-14.22 +/- 2.63 and -15.11 +/- 2.45, respectively, p >
      0.05). The results revealed significant changes in GLS during exercise in
      patients with repaired TOF. Data gathered from deformation analysis of 2D-STE
      during exercise testing can enhance the ability to detect subtle ventricular
      dysfunction in the follow-up of children with repaired TOF.

PMID- 27878629
TI  - Clinical Outcomes in Pediatric Patients Hospitalized with Fulminant Myocarditis
      Requiring Extracorporeal Membrane Oxygenation: A Meta-analysis.
AB  - We conducted a meta-analysis to provide the survival rates for pediatric patients
      hospitalized with fulminant myocarditis requiring ECMO. The literature search was
      conducted using Embase, PubMed, MEDLINE and Elsevier for studies published before
      April 1, 2016. We focus on survival rates for pediatric patients hospitalized
      with fulminant myocarditis requiring ECMO, and studies that reported only on
      adult patients were excluded. Summary of the survival rates was obtained using
      fixed-effect or random-effect meta-analysis which determined by I 2. Six studies
      were included in the analysis, encompassing 172 patients. The minimum and maximum
      reported rates of survival to hospital discharge were 53.8 and 83.3%,
      respectively. The cumulative rate was 107/172. The calculated Cochran Q value was
      3.73, which was not significant for heterogeneity (P = 0.588). The I 2 value was
      0%. The pooled estimate rate was 62.9% with a 95% confidence interval of 55.3
      69.8%. In pediatric patients with cardiac failure who have failed conventional
      therapies in FM, venoarterial ECMO should be considered. In total, 62.9% of
      patients with FM and either cardiogenic shock and/or cardiac arrest survived to
      hospital discharge with ECMO.

PMID- 27878630
TI  - Diagnostic and Prognostic Value of Plasma Levels of Cardiac Myosin Binding
      Protein-C as a Novel Biomarker in Heart Failure.
AB  - Heart failure (HF) has high morbidity and mortality in children. This study aimed
      to investigate the value of cardiac myosin binding protein-C (cMyBP-C) as a
      diagnostic and prognostic biomarker in children with heart failure. This study
      was a prospective case-control study that involved 50 children with acute HF and
      25 healthy children of matched age and sex as a control group. cMyBP-C plasma
      levels were measured in patients with HF at the time of admission and 1 month
      after treatment. Echocardiographic assessment was done for all children. All
      patients were followed up for a period of 3 months. There was a significant
      increase in plasma levels of cMyBP-C (ng/ml) in patients with HF at admission
      (122.44 +/- 41.01) as compared to patients after treatment (71.38 +/- 49.68) and
      to control group (24.40 +/- 9.83). This increase was associated with increased
      severity of HF according to pediatric Ross classification of HF. Significant
      increase in plasma levels of cMyBP-C at admission and its persistent increase
      after treatment were associated with adverse outcome of mortality and
      readmission. Plasma levels of cMyBP-C were significantly correlated with
      echocardiographic and clinical assessment of heart failure. Plasma levels of
      cMyBP-C were a good biomarker for diagnosis of HF with sensitivity 100% and
      specificity 96% at cutoff point of 45 ng/ml. Its value in predicting adverse
      outcome in HF patients was obtained by ROC curve with sensitivity of 90% and
      specificity 93% at a cutoff point of 152 ng/ml cMyBP-C at admission. cMyBP-C may
      be a novel useful diagnostic and prognostic biomarker in children with heart
      failure and determination of severity of HF in these patients.

PMID- 27878631
TI  - Difference in Risk Factors for Subtypes of Acute Cardiac Lesions Resulting from
      Kawasaki Disease.
AB  - Few studies discuss the risk factors for acute cardiac lesions (within 30 days)
      resulting from Kawasaki disease (KD). We aimed to clarify the characteristics of
      patients with cardiac lesions within 30 days and determine the risk factors for
      acute cardiac lesion subtypes. Using the 23rd nationwide survey of KD in Japan,
      we analyzed data from patients with or without acute cardiac lesions resulting
      from KD (n = 31,380). We subdivided patients with acute cardiac lesions into
      three types: acute valvular lesions, coronary aneurysms, and giant coronary
      aneurysms (GCA), and calculated the odds ratios of potential risk factors for
      acute cardiac lesion subtypes. The prevalence of acute cardiac lesions was 8.6%,
      and these lesions were more prevalent among males than females (1.98:1). Male
      sex, age <1 year, and atypical definite cases predicted coronary artery lesions
      (CAL). The risk factors for valvular lesions differed from the risk factors for
      CALs, but GCA risk factors were similar to CAL risk factors: age <1 year, later
      presentation to hospital, atypical definite cases, and resistance to initial
      intravenous immunoglobulin (IVIG) therapy. Resistance to IVIG therapy was a
      significant risk factor for acute GCA. We found differences in cardiac lesion
      risk factors within 30 days of diagnosing KD between acute CAL and valvular
      lesions resulting from KD. In particular, pediatricians should consider atypical
      definite cases and resistance to initial IVIG when assessing the risk of acute
      phase GCA.

PMID- 27878632
TI  - Utility of Echocardiography in the Assessment of Left Ventricular Diastolic
      Function and Restrictive Physiology in Children and Young Adults with Restrictive
      Cardiomyopathy: A Comparative Echocardiography-Catheterization Study.
AB  - The aim of the study is to determine the utility of echocardiography in the
      assessment of diastolic function in children and young adults with restrictive
      cardiomyopathy (RCM). RCM is a rare disease with high mortality requiring
      frequent surveillance. Accurate, noninvasive echocardiographic measures of
      diastolic function may reduce the need for invasive catheterization. Single
      center, prospective, observational study of pediatric and young adult RCM
      patients undergoing assessment of diastolic parameters by simultaneous
      transthoracic echocardiogram (TTE) and invasive catheterization. Twenty-one
      studies in 15 subjects [median (IQR) = 13.8 years (7.0-19.2), 60% female] were
      acquired with median left ventricular end-diastolic pressure (LVEDP) 21 (IQR 18
      25) mmHg. TTE parameters of diastolic function, including pulmonary vein A wave
      duration (r s  = 0.79) and indexed left atrial volume (r s  = 0.49), demonstrated
      significant positive correlation, while mitral valve A (r s  = -0.44), lateral e'
      (r s  = -0.61) and lateral a' (r s  = -0.61) velocities showed significant
      negative correlation with LVEDP. Lateral a' velocity (<=0.042 m/s) and pulmonary
      vein A wave duration (>=156 m/s) both had sensitivity and specificity >=80% for
      LVEDP >= 20 mmHg. In pediatric and young adult patients with RCM, lateral a'
      velocity and pulmonary vein A wave duration predicted elevated LVEDP with high
      sensitivity and specificity; however, due to technical limitations the latter was
      reliably measured in 12/21 patients. These noninvasive parameters may have
      utility in identifying patients that require further assessment with invasive
      testing. These findings require validation in a multicenter prospective cohort
      prior to widespread clinical implementation.

PMID- 27878633
TI  - Cardiopulmonary Exercise Testing in Fontan Patients With and Without Isomerism
      (Heterotaxy) as Compared to Patients With Primary Ciliary Dyskinesia and Subjects
      With Structurally Normal Hearts.
AB  - Isomerism, also known as heterotaxy, is a clinical entity that impacts multiple
      organ systems both anatomically and functionally. The airways and lungs are
      involved in a great number of these patients, leading to increased sinopulmonary
      symptoms, increased need for oxygenation, and increased postoperative ventilatory
      support. Additionally, these patients often have congenital heart disease
      requiring Fontan palliation. What has not been previously described, and is the
      focus of this study, is the results of cardiopulmonary exercise testing in those
      who have undergone Fontan palliation with and without isomerism. We have now
      compared these finding with those from patients with primary ciliary dyskinesia,
      as many patients with isomerism have ciliary dyskinesia. We identified patients
      having the Fontan circulation with and without isomerism who had undergone
      cardiopulmonary exercise testing, comparing the findings from healthy individuals
      undergoing exercise, and a comparable number of individuals with primary ciliary
      dyskinesia but no congenital heart disease. We were able to include a total of 68
      patients in our study, with 17 in each of the four groups. Cardiopulmonary
      exercise testing yielded the best results in healthy patients. All patients with
      the Fontan circulation demonstrated mixed pulmonary disease, although those with
      isomerism had greater FVC and FEV1. Exercise times did not differ, although peak
      consumption of oxygen was greater in those with isomerism. Those with ciliary
      dyskinesia had only obstructive pulmonary disease and had the lowest FEF25-75
      between all groups. Those with isomerism had a lesser degree of obstructive
      pulmonary disease when compared to those with primary ciliary dyskinesia.
      Patients with the Fontan circulation with and without isomerism have relatively
      subtle differences in their cardiopulmonary exercise testing, with both groups
      demonstrating restrictive lung disease. In regard to obstructive lung disease,
      those with isomerism tend to be more similar to the patients with primary ciliary
      dyskinesia than those with the Fontan circulation but without isomerism. The
      results are likely limited by selection bias and highlight the need for
      multicentric efforts to characterize cardiopulmonary exercise testing in those
      patients with pulmonary isomerism.

PMID- 27878635
TI  - The focal hepatic hot spot ("hot quadrate") sign.

PMID- 27878634
TI  - Relationship Between Habitual Exercise and Performance on Cardiopulmonary
      Exercise Testing Differs Between Children With Single and Biventricular
      Circulations.
AB  - Increasing habitual exercise has been associated with improved cardiopulmonary
      exercise testing (CPET) performance, specifically maximal oxygen consumption in
      children with operatively corrected congenital heart disease. This has not been
      studied in children following Fontan palliation, a population in whom CPET
      performance is dramatically diminished. A single-center cross-sectional study
      with prospective and retrospective data collection was performed that assessed
      habitual exercise preceding a clinically indicated CPET in children and
      adolescents with Fontan palliation, transposition of the great arteries following
      arterial switch operation (TGA), and normal cardiac anatomy without prior
      operation. Data from contemporaneous clinical reports and imaging studies were
      collected. The association between percent predicted VO2max and habitual exercise
      duration adjusted for known covariates was tested. A total of 175 subjects (75
      post-Fontan, 20 with TGA, and 80 with normal cardiac anatomy) were enrolled.
      VO2max was lower in the Fontan group than patients with normal cardiac anatomy (p
      < 0.0001) or TGA (p < 0.0001). In Fontan subjects, both univariate and
      multivariate analysis failed to demonstrate a significant association between
      habitual exercise and VO2max (p = 0.6), in sharp contrast to cardiac normal
      subjects. In multivariate analysis, increasing age was the only independent risk
      factor associated with decreasing VO2max in the Fontan group (p = 0.003).
      Habitual exercise was not associated with VO2max in subjects with a Fontan as
      compared to biventricular circulation. Further research is necessary to
      understand why their habitual exercise is ineffective and/or what aspects of the
      Fontan circulation disrupt this association.

PMID- 27878636
TI  - Imaging of secretory tumors of the gastrointestinal tract.
AB  - Gastrointestinal secretory tumors, or gastroenteropancreatic neuroendocrine
      tumors, encompass a wide array of endocrine cell tumors. The significance of
      these tumors lies in their ability to alter physiology through hormone production
      as we well as in their malignant potential. Functioning tumors may present
      earlier due to symptomatology; conversely, non-functioning tumors are often
      diagnosed late as they reach large sizes, causing symptoms secondary to local
      mass effect. Imaging aids in the diagnosis, staging, and prognosis and provides
      key information for presurgical planning. Although most of these tumors are
      sporadic, some are associated with important syndromes and associations,
      knowledge of which is critical for patient management. In this article, we
      provide an overview of secretory and neuroendocrine tumors of the GI tract and
      pancreas.

PMID- 27878637
TI  - Optimization of window settings for standard and advanced virtual monoenergetic
      imaging in abdominal dual-energy CT angiography.
AB  - OBJECTIVES: To determine the optimal window setting for displaying virtual
      monoenergetic reconstructions of third generation dual-source, dual-energy CT
      (DECT) angiography of the abdomen. METHODS: Forty-five patients were evaluated
      with DECT angiography (90/150 kV, 180/90 ref. mAs). Three datasets were
      reconstructed: standard linear blending (M_0.6), 70 keV traditional virtual
      monoenergetic (M70), and 40 keV advanced noise-optimized virtual monoenergetic
      (M40+). The best window setting (width and level, W/L) was assessed by two
      blinded observers and was correlated with aortic attenuation to obtain the
      Optimized W/L setting (O-W/L). Subjective image quality was assessed, and vessel
      diameters were measured to determine any possible influences between different
      W/L settings. Repeated measures of variance were used to evaluate comparison of
      W/L values, image quality, and vessel sizing between M_0.6, M70, and M40+.
      RESULTS: The Best W/L (B-W/L) for M70 and M40+ was 880/280 and 1410/450,
      respectively. Results from regression analysis inferred an O-W/L of 850/270 for
      M70 and 1350/430 for M40+. Significant differences for W and L were found between
      the Best and the Optimized W/L for M40+, and between M70 and M40+ for both the
      Best and Optimized W/L. No significant differences for vessel measurements were
      found using the O-W/L for M40+ compared to the standard M_0.6 (p >= 0.16), and
      significant differences were observed when using the B-W/L with M40+ compared to
      M_0.6 (p <= 0.04). CONCLUSION: In order to optimize virtual monoenergetic imaging
      with both traditional M70 and advanced M40+, adjusting the W/L settings is
      necessary. Our results suggest a W/L setting of 850/270 for M70 and 1350/430 for
      M40+.

PMID- 27878638
TI  - Evolution of DS-1-like G1P[8] double-gene reassortant rotavirus A strains causing
      gastroenteritis in children in Vietnam in 2012/2013.
AB  - Rotavirus A (RVA) strains, a leading cause of severe gastroenteritis in children
      worldwide, commonly possess the Wa or DS-1 genotype constellations. During a
      hospital-based study conducted in Hanoi, Vietnam, in the 2012-2013 rotavirus
      season, G1P[8] strains with a virtually identical short RNA migration pattern
      were detected in 20 (14%) of 141 rotavirus-positive samples. Two representatives
      of these strains were shown by whole-genome sequencing to be double-gene
      reassortants possessing the genotype constellation of G1-P[8]-I2-R2-C2-M2-A2-N2
      T2-E2-H2. Sequencing and a database search revealed that these Vietnamese G1P[8]
      double-gene reassortant strains shared an immediate ancestor with a locally
      circulating G2P[4] strain in all of the inner-capsid and non-structural protein
      genes, whereas they were more closely related in the VP7 and VP4 genes to a
      Chinese G1P[8] strain and a Chinese G3P[8] strain, respectively, than to locally
      circulating G1P[8] strains. Despite the marked similarity between Japanese and
      Thai G1P[8] double-gene reassortant strains, phylogenetic analysis suggested that
      the Vietnamese and Japanese/Thai G1P[8] double-gene reassortant strains
      originated from independent reassortment events. Clinically, children infected
      with Vietnamese G1P[8] double-gene reassortant strains experienced severe
      diarrhoea, but it was not more severe than that in children infected with
      ordinary G1P[8] strains. In conclusion, Vietnamese G1P[8] double-gene reassortant
      strains originated from a locally circulating G2P[4] strain and caused severe
      diarrhoea, but there was no evidence of increased virulence.

PMID- 27878639
TI  - Association Between Depression and Condom Use Differs by Sexual Behavior Group in
      Patients with HIV.
AB  - Identifying a relationship between depression and sexual risk behavior in HIV
      infected patients could establish a mechanism to enhance prevention efforts. We
      conducted a cross-sectional analysis using data from the University of
      Pennsylvania Center for AIDS Research and used ordinal logistic regression to
      measure the association between depression and non-condom use. 716 men who have
      sex with men (MSM), 262 heterosexual men and 277 heterosexual women were
      included. The association between depression and non-condom use was strongest in
      heterosexual men with and without HIV-infected regular partners (OR 8.53, 95% CI
      1.18-61.89 and OR 2.30, 95% CI 0.99-5.36 respectively), but absent in
      heterosexual women regardless of partner. Although the OR was low in MSM overall,
      an association was detected in MSM without HIV-infected regular partners (OR
      2.44, 95% CI 1.39-4.31). In conclusion, we demonstrated an association between
      depression and non-condom use driven by heterosexual men and MSM without HIV
      infected regular partners. Sexual risk should be addressed when intervening on
      depressive symptoms in these subgroups.

PMID- 27878640
TI  - In-vitro examination of the biocompatibility of fibroblast cell lines on
      alloplastic meshes and sterilized polyester mosquito mesh.
AB  - INTRODUCTION: The use of alloplastic implants for tissue strengthening when
      treating hernias is an established therapy worldwide. Despite the high incidence
      of hernias in Africa and Asia, the implantation of costly mesh netting is not
      financially feasible. Because of that various investigative groups have examined
      the use of sterilized mosquito netting. The animal experiments as well as the
      clinical trials have both shown equivalent short- and long-term results. The goal
      of this paper is the comparison of biocompatibility of human fibroblasts on the
      established commercially available nets and on sterilized polyester mosquito mesh
      over a period of 12 weeks. MATERIALS AND METHODS: Three commercially available
      plastic mesh types and a gas-sterilized mosquito polyethylenterephtalate
      (polyester) mesh were examined. Human fibroblasts from subcutaneous healthy
      tissue were used. Various tests for evaluating the growth behavior and the cell
      morphology of human fibroblasts were conducted. The semi-quantitative (light
      microscopy) and qualitative (scanning electron microscopy) analyses were
      performed after 1 week and then again after 12 weeks. The cell proliferation and
      cytotoxicity of the implants were investigated with the help of the 5'-bromo-2'
      deoxyuridine (BrdU)-cell proliferation test and the LDH-cytotoxicity test. The
      number of live cells per ml was determined with the Burker counting chamber. In
      addition, analyses were made of the cell metabolism (oxidative stress) by
      measuring the pH value, hydrogen peroxide, and glycolysis. RESULTS: After 12
      weeks, a proliferation of fibroblasts on all mesh is documented. No mesh showed a
      complete apoptosis of the cells. This qualitative observation could be confirmed
      quantitatively in a biochemical assay by marking the proliferating cells with
      BrdU. The biochemical analysis brought the proof that the materials used,
      including the polyester of the mosquito mesh, are not cytotoxic for the
      fibroblasts. The vitality of the cells was between 94 and 98%. The glucose
      metabolism as well as the pH value of the fibroblasts showed no significant
      differences between the tested meshes. The examination of the oxidative stress
      via measurement of the H2O2 concentration showed values in the normal range for
      the commercially alloplastic meshes and the mosquito mesh. CONCLUSIONS: Our
      examination showed no significant difference with regard to biocompatibility
      between the officially approved and cost-intensive meshes and the sterilized
      (autoclaved) mosquito mesh. Due to the proven strength and stability of the
      mosquito mesh and their proven compatibility, the implantation of the sterilized
      mosquito mesh in additional in vivo studies must be considered. A wide-scale and
      cost-effective treatment of hernias could thus be guaranteed, not only in Third
      World countries.

PMID- 27878641
TI  - Dental arch spatial changes after premature loss of first primary molars: a
      systematic review of controlled studies.
AB  - Studies investigating dental arch spatial changes following first primary molar
      premature loss are controversial regarding clinical significance. The purpose of
      this review was to systematically investigate the relevant literature. Controlled
      studies investigating changes before and after premature loss of first primary
      molars were searched in various databases. Split-mouth design studies were
      considered eligible for inclusion. The risk of bias was judged according to ADA
      Clinical Practice Guidelines. Only two analyzable split-mouth studies on
      mandibular first primary molar loss were identified. Space loss in the extraction
      side was greater at 2, 4, 6 and 8-month follow-ups, reaching a -1.5 mm difference
      in the final examination (95% Confidence Interval: -2.080 to -0.925; p = 0.000;
      random effects model). Studies were judged to be at unclear risk of bias. The
      amount of space decrease after premature loss of first primary molars may have
      management implications under certain circumstances. Comprehensive assessment of
      the various characteristics of each patient should precede management decisions
      in individual cases.

PMID- 27878643
TI  - The evolution of drug design at Merck Research Laboratories.
AB  - On October 5, 1981, Fortune magazine published a cover article entitled the "Next
      Industrial Revolution: Designing Drugs by Computer at Merck". With a 40+ year
      investment, we have been in the drug design business longer than most. During its
      history, the Merck drug design group has had several names, but it has always
      been in the "design" business, with the ultimate goal to provide an actionable
      hypothesis that could be tested experimentally. Often the result was a small
      molecule but it could just as easily be a peptide, biologic, predictive model,
      reaction, process, etc. To this end, the concept of design is now front and
      center in all aspects of discovery, safety assessment and early clinical
      development. At present, the Merck design group includes computational chemistry,
      protein structure determination, and cheminformatics. By bringing these groups
      together under one umbrella, we were able to align activities and capabilities
      across multiple research sites and departments. This alignment from 2010 to 2016
      resulted in an 80% expansion in the size of the department, reflecting the
      increase in impact due to a significant emphasis across the organization to
      "design first" along the entire drug discovery path from lead identification
      (LID) to first in human (FIH) dosing. One of the major advantages of this
      alignment has been the ability to access all of the data and create an adaptive
      approach to the overall LID to FIH pathway for any modality, significantly
      increasing the quality of candidates and their probability of success. In this
      perspective, we will discuss how we crafted a new strategy, defined the
      appropriate phenotype for group members, developed the right skillsets, and
      identified metrics for success in order to drive continuous improvement. We will
      not focus on the tactical implementation, only giving specific examples as
      appropriate.

PMID- 27878644
TI  - Erratum to: Subsequent risk of ipsilateral and contralateral invasive breast
      cancer after treatment for ductal carcinoma in situ: incidence and the effect of
      radiotherapy in a population-based cohort of 10,090 women.

PMID- 27878642
TI  - Are Th17 Cells Playing a Role in Immunity to Dermatophytosis?
AB  - Despite their superficial localization in the skin, pathogenic dermatophytes can
      induce a complex but still misunderstood immune response in their hosts. The cell
      mediated immunity (CMI) is correlated with both clinical recovery and protection
      against reinfection, and CD4+ T lymphocytes have been recognized as a crucial
      component of the immune defense against dermatophytes. Before the discovery of
      the Th17 pathway, CMI was considered to be only dependent of Th1 cells, and thus
      most studies on the immunology of dermatophytosis have focused on the Th1
      pathway. Nevertheless, the fine comparative analysis of available scientific data
      on immunology of dermatophytosis in one hand and on the Th17 pathway mechanisms
      involved in opportunistic mucosal fungal infections in the other hand reveals
      that some key elements of the Th17 pathway can be activated by dermatophytes.
      Stimulation of the Th17 pathway could occur through the activation of some C-type
      lectin-like receptors and inflammasome in antigen-presenting cells. The Th17
      cells could go back to the affected skin and by the production of signature
      cytokines could induce the effector mechanisms like the recruitment of
      polymorphonuclear neutrophils and the synthesis of antimicrobial peptides. In
      conclusion, besides the Th1 pathway, which is important to the immune response
      against dermatophytes, there are also growing evidences for the involvement of
      the Th17 pathway.

PMID- 27878645
TI  - The Synaptojanins in the murine small and large intestine.
AB  - The expression of the phosphoinositides phosphatases Synaptojanins (Synjs) 1 and
      2 has been shown in brain and in some peripheral tissues, but their expression in
      the intestine has not been reported. Herein we show that the small and large
      intestine express Synj1 and Synj2. Their mRNA levels, measured by RT-PCR, are not
      affected by development in the small intestine but in the colon they increase
      with age. Immunostaining assays reveal that both Synjs localize at the apical
      domain of the epithelial cells and at the lamina propria at sites also expressing
      the neuron marker calretinin. Synj2 staining at the lamina propria is fainter
      than that of Synj1. In colonocytes Synjs are at the apical membrane and cytosolic
      membrane vesicles. Synj2 is also at the mitochondria. Western blots reveal that
      the intestinal mucosa expresses at least two Synj1 (170- and 139-kDa) and two
      Synj2 (160- and 148-kDa) isoforms. The observations suggest that Synj1-170, Synj2
      160, and Synj2-148 in colonocytes, might participate in processes that take place
      mainly at the apical domain of the epithelial cells whereas Synj1-139 in those at
      the enteric nervous system. Experimental colitis augments the mRNA abundance of
      both Synjs in colon but only Synj2 mRNA levels are increased in colon tumors. In
      conclusion, as far as we know, this is the first report showing expression,
      location and isoforms of Synj1 and Synj2 in the small and large intestine and
      that they might participate in intestinal pathology.

PMID- 27878646
TI  - Using Search Engine Query Data to Explore the Epidemiology of Common
      Gastrointestinal Symptoms.
AB  - BACKGROUND: Internet searches are an increasingly used tool in medical research.
      To date, no studies have examined Google search data in relation to common
      gastrointestinal symptoms. AIMS: The aim of this study was to compare trends in
      Internet search volume with clinical datasets for common gastrointestinal
      symptoms. METHODS: Using Google Trends, we recorded relative changes in volume of
      searches related to dysphagia, vomiting, and diarrhea in the USA between January
      2008 and January 2011. We queried the National Inpatient Sample (NIS) and the
      National Hospital Ambulatory Medical Care Survey (NHAMCS) during this time period
      and identified cases related to these symptoms. We assessed the correlation
      between Google Trends and these two clinical datasets, as well as examined
      seasonal variation trends. RESULTS: Changes to Google search volume for all three
      symptoms correlated significantly with changes to NIS output (dysphagia: r = 0.5,
      P = 0.002; diarrhea: r = 0.79, P < 0.001; vomiting: r = 0.76, P < 0.001). Both
      Google and NIS data showed that the prevalence of all three symptoms rose during
      the time period studied. On the other hand, the NHAMCS data trends during this
      time period did not correlate well with either the NIS or the Google data for any
      of the three symptoms studied. Both the NIS and Google data showed modest
      seasonal variation. CONCLUSIONS: Changes to the population burden of chronic GI
      symptoms may be tracked by monitoring changes to Google search engine query
      volume over time. These data demonstrate that the prevalence of common GI
      symptoms is rising over time.

PMID- 27878647
TI  - Predicting Suboptimal Bowel Preparation: Taking It Up a PEG.

PMID- 27878648
TI  - Jaundice and Pregnancy: Why Going Viral Is Out of Style.

PMID- 27878649
TI  - 15N and 13C- SOFAST-HMQC editing enhances 3D-NOESY sensitivity in highly
      deuterated, selectively [1H,13C]-labeled proteins.
AB  - The ongoing NMR method development effort strives for high quality
      multidimensional data with reduced collection time. Here, we apply 'SOFAST-HMQC'
      to frequency editing in 3D NOESY experiments and demonstrate the sensitivity
      benefits using highly deuterated and 15N, methyl labeled samples in H2O. The
      experiments benefit from a combination of selective T 1 relaxation (or L
      optimized effect), from Ernst angle optimization and, in certain types of
      experiments, from using the mixing time for both NOE buildup and magnetization
      recovery. This effect enhances sensitivity by up to 2.4* at fast pulsing versus
      reference HMQC sequences of same overall length and water suppression
      characteristics. Representative experiments designed to address interesting
      protein NMR challenges are detailed. Editing capabilities are exploited with
      heteronuclear 15N,13C-edited, or with diagonal-free 13C aromatic/methyl-resolved
      3D-SOFAST-HMQC-NOESY-HMQC. The latter experiment is used here to elucidate the
      methyl-aromatic NOE network in the hydrophobic core of the 19 kDa FliT-FliJ
      flagellar protein complex. Incorporation of fast pulsing to reference experiments
      such as 3D-NOESY-HMQC boosts digital resolution, simplifies the process of NOE
      assignment and helps to automate protein structure determination.

PMID- 27878650
TI  - Ultra-high magnetic resonance imaging (MRI): a potential examination for deep
      brain stimulation devices and the limitation study concerning MRI-related heating
      injury.
AB  - Nowadays, the patients with deep brain stimulation (DBS) devices are restricted
      to undertake 1.5T magnetic resonance imaging (MRI) according to the guideline.
      Nevertheless, we conducted an experiment to test pathological change near the
      leads in different field-strength MRI. Twenty-four male New Zealand rabbits were
      assigned to Group 1 (G1, n = 6, 7.0T, DBS), Group 2 (G2, n = 6, 3.0T, DBS), Group
      3 (G3, n = 6, 1.5T, DBS), and Group 4 (G4, n = 6, 1.5T, paracentesis). DBS leads
      were implanted in G1, G2 and G3, targeting left nucleus ventralis posterior
      thalami. Paracentesis was performed in G4. 24 h after MRI scan, all animals were
      killed for examining pathological alternation (at different distance from lead)
      via transmission electron microscopy. Our results suggest that the severity of
      tissue injury correlates with the distance to electrode instead of field strength
      of MRI. Up to now, the reason for the restriction of MRI indicated no
      significantly different pathological change.

PMID- 27878653
TI  - Single-cell RNA-seq reveals lincRNA expression differences in Hela-S3 cells.
AB  - OBJECTIVE: To characterize transcriptome-wide lincRNAs of Hela-S3 cell line by
      analyzing RNA sequencing data to provide a foundation for further functional
      verification and clinical application of cervical carcinoma development. RESULTS:
      Single-cell RNA sequencing data of 37 Hela-S3 cells were analysed. On average,
      511 lincRNAs were expressed in each cell. Comparing the expression difference of
      the lincRNAs and protein-coding genes, we found that lincRNAs expression
      displayed more cell specificity than that of protein-coding genes (t-test, P<2.2E
      16). In co-expression network analysis, we identified seven modules and one of
      them was enriched in pathways of mitotic, packaging of telomere ends, and
      chromosome maintenance. CONCLUSION: incRNAs are specifically expressed and form a
      network to perform function at single cell level. Their expression was more
      specific than that of protein-coding genes.

PMID- 27878651
TI  - Messages on small RNA duplexes in plants.
AB  - Small RNA-mediated gene silencing encompasses diverse developmental events,
      stress responses, defense against pathogens, and maintenance of genome integrity.
      Extensive studies in model organisms have unveiled the molecular mechanisms
      underpinning the RNA silencing phenomena, and the accumulating knowledge have
      characterized the intricate pathways and the repertoire of proteins responsible
      for the actions of small RNAs characterized as microRNAs (miRNAs) or small
      interfering RNAs (siRNAs). Although the single-stranded, matured guide small RNAs
      direct the effector ribonucleoprotein complexes to induce gene silencing in
      sequence-specific manner, the double-stranded intermediate, the small RNA
      duplexes, which are processed as nascent products of the RNase III enzyme
      activities, act as key to determine the downstream molecular pathways and the
      fate of small RNAs. Based at the small RNA duplex-centered view, this review
      describes the recent advances in understanding the small RNA pathways in plants.

PMID- 27878654
TI  - Coating polypropylene surfaces with protease weakens the adhesion and increases
      the dispersion of Candida albicans cells.
AB  - OBJECTIVES: To investigate the ability of the proteases, subtilisin and alpha
      chymotrypsin (aCT), to inhibit the adhesion of Candida albicans biofilm to a
      polypropylene surface. RESULTS: The proteases were immobilized on plasma-treated
      polypropylene by covalently linking them with either glutaraldehyde (GA) or N'
      diisopropylcarbodiimide (DIC) and N-hydroxysuccinimide (NHS). The immobilization
      did not negatively affect the enzyme activity and in the case of subtilisin, the
      activity was up to 640% higher than that of the free enzyme when using N-acetyl
      phenylalanine ethyl ester as the substrate. The efficacies against biofilm
      dispersal for the GA-linked SubC and aCT coatings were 41 and 55% higher than the
      control (polypropylene coated with only GA), respectively, whereas no effect was
      observed with enzymes immobilized with DIC and NHS. The higher dispersion
      efficacy observed for the proteases immobilized with GA could be both steric
      (proper orientation of the active site) and dynamic (higher protein
      mobility/flexibility). CONCLUSIONS: Proteases immobilized on a polypropylene
      surface reduced the adhesion of C. albicans biofilms and therefore may be useful
      in developing anti-biofilm surfaces based on non-toxic molecules and sustainable
      strategies.

PMID- 27878655
TI  - The use of donor scleral patch in ophthalmic surgery.
AB  - Scleral tissue has been in use in ophthalmology for many years although
      indications for use have varied. We retrospectively reviewed scleral transplant
      tissue requests over a 12 month period at a local eye bank and confirmed a small
      but significant demand for the use of scleral tissue. Iatrogenic surgical
      complications are the primary indication for use. Our understanding of the
      indications and outcomes of scleral graft procedures is derived from case reports
      and small cohort series. We reviewed the current literature on existing
      indications for its use and discuss the relative outcomes. To our knowledge this
      represents the first review of scleral transplant indications and further
      summarises usage rates in the Lions NSW Eye Bank which may provide practical
      information for those surgeons who use scleral tissue and Eye Banks who supply
      it.

PMID- 27878652
TI  - Genome-wide identification and phylogenetic analysis of the chalcone synthase
      gene family in rice.
AB  - The enzymes of the chalcone synthase family are also known as type III polyketide
      synthases (PKS), and produce a series of secondary metabolites in bacteria, fungi
      and plants. In a number of plants, genes encoding PKS comprise a large multigene
      family. Currently, detailed reports on rice (Oryza sativa) PKS (OsPKS) family
      genes and tissue expression profiling are limited. Here, 27 candidate OsPKS genes
      were identified in the rice genome,and 23 gene structures were confirmed by EST
      and cDNA sequencing; phylogenetic analysis has indicated that these 23 OsPKS
      members could be clustered into three groups (I-III). Comparative analysis has
      shown OsPKS08 and OsPKS26 could be classified with the CHS genes of other
      species. Two members OsPKS10 and OsPKS21 were grouped into anther specific
      chalcone synthase-like (ASCL) clade. Intron/exon structure analysis revealed that
      nearly all of the OsPKS members contained one phase-1 intron at a conserved Cys.
      Analysis of chromosomal localization and genome distribution showed that some of
      the members were distributed on a chromosome as a cluster. Expression data
      exhibited widespread distribution of the rice OsPKS gene family within plant
      tissues, suggesting functional diversification of the OsPKS genes. Our results
      will contribute to future study of the complexity of the OsPKS gene family in
      rice.

PMID- 27878656
TI  - Mille modis morimur: We die in a thousand ways.
AB  - Dying cells subjected to apoptotic programs are engulfed by neighboring cells or
      by professional phagocytes, without inflammation or immunological reactions in
      the tissue where apoptosis takes place. Apoptotic cells release danger-associated
      project signals to their neighbours, through different molecular patterns,
      stimulate antigen production and immune responses. Microenvironmental effects
      with several functional consequences indicate that cell death is a complex
      process and may take place in several ways. This idea is expressed by the title
      of the Special Issue and by the title of the guest editorial "Mille modis
      morimur" meaning that not only multicellular organisms, but also single cells may
      die in a thousand ways. This idea is demonstrated by the papers serving as
      examples for cell death. Apoptosis was induced by clary sage oil in Candida
      cells. Heavy metal (Gd) induced cell motility and apoptosis was found in
      mammalian cells. RNA oxidation enhanced the reversion frequency of apoptosis in
      yeast mutants. The frequency of apoptotic micronucleus formation increased in a
      concentration-dependent manner by methotrexate. The antioxidant coenzyme Q10
      protected renal proximal tubule cells against nicotine-induced apoptosis. The
      synergy of 2-deoxy-D-glucose combined with berberine induced lysosome/autophagy.
      The mitochondrial apoptotic pathway could be regulated by glucocorticoid receptor
      in collaboration with Bcl-2 family proteins in developing T cells.
      Cylindrospermopsin induced biochemical changes led to apoptosis in plants.
      Mechanisms of stress seriously impacted the risk of apoptosis. Transcriptional
      control of apoptotic cell clearance was achieved by macrophage nuclear receptors.
      Finally, the clinical aspects of apoptosis-induced lymphopenia were reviewed in
      sepsis and other severe injuries. These examples not only support the view of
      many ways of cell death, but predict further potential ways to induce or reduce
      the risk of cell death.

PMID- 27878657
TI  - C3 glomerulopathy and current dilemmas.
AB  - C3 glomerulopathy (C3G) is a recently identified disease entity caused by
      dysregulation of the alternative complement pathway, and dense deposit disease
      (DDD) and C3 glomerulonephritis (C3GN) are its components. Because laboratory
      detection of complement dysregulation is still uncommon in practice, "dominant C3
      deposition by two orders greater than that of immunoglobulins in the glomeruli by
      immunofluorescence", as stated in the consensus report, defines C3G. However,
      this morphological definition possibly includes the cases with glomerular
      diseases of different mechanisms such as post-infectious glomerulonephritis. In
      addition, the differential diagnosis between DDD and C3GN is often difficult
      because the distinction between these two diseases is based solely on electron
      microscopic features. Recent molecular and genetic advances provide information
      to characterize C3G. Some C3G cases are found with genetic abnormalities in
      complement regulatory factors, but majority of cases seem to be associated with
      acquired factors that dysregulate the alternative complement pathway. Because
      clinical courses and prognoses among glomerular diseases with dominant C3
      deposition differ, further understanding the background mechanism, particularly
      complement dysregulation in C3G, is needed. This may resolve current dilemmas in
      practice and shed light on novel targeted therapies to remedy the dysregulated
      alternative complement pathway in C3G.

PMID- 27878660
TI  - Residual bone growth after lengthening procedures.
AB  - The prognosis of limb length discrepancy is a major subject in paediatric
      orthopaedic surgery. The strategy depends on the prognosis and must be adapted to
      each patient. The residual growth of the lengthened segment often remains
      unknown, but is dependent on age, the percentage of lengthening and other
      factors. Using a large cohort of 150 children who had undergone bone lengthening
      procedures, we describe five patterns of post-intervention growth and identify
      factors that are favourable for normal residual growth. The criteria for bone
      lengthening which should maintain good residual growth are-bone age at
      lengthening should be before the pubertal growth spurt; the interval between two
      lengthening procedures should be over three years; the percentage of lengthening
      should be <30% of the initial segment; and no more than two lengthening
      procedures should be carried out during infancy.

PMID- 27878659
TI  - Neural Signaling Metabolites May Modulate Energy Use in Hibernation.
AB  - Despite an epidemic in obesity and metabolic syndrome limited means exist to
      effect adiposity or metabolic rate other than life style changes. Here we review
      evidence that neural signaling metabolites may modulate thermoregulatory pathways
      and offer novel means to fine tune energy use. We extend prior reviews on
      mechanisms that regulate thermogenesis and energy use in hibernation by focusing
      primarily on the neural signaling metabolites adenosine, AMP and glutamate.

PMID- 27878661
TI  - Phosphate starvation induced OsPHR4 mediates Pi-signaling and homeostasis in
      rice.
AB  - KEY MESSAGE: OsPHR4 mediates the regulation of Pi-starvation signaling and Pi
      homeostasis in a PHR1-subfamily dependent manner in rice. Phosphate (Pi)
      starvation response is a sophisticated process for plant in the natural
      environment. In this process, PHOSPHATE STARVATION RESPONSE 1 (PHR1) subfamily
      genes play a central role in regulating Pi-starvation signaling and Pi
      homeostasis. Besides the three PHR1 orthologs in Oryza sativa L. (Os) [(Os) PHR1,
      (Os) PHR2, and (Os) PHR3], which were reported to regulated Pi-starvation
      signaling and Pi-homeostasis redundantly, a close related PHR1 ortholog
      [designated as (Os) PHR4] is presented in rice genome with unknown function. In
      this study, we found that OsPHR4 is a Pi-starvation induced gene and mainly
      expresses in vascular tissues through all growth and development periods. The
      expression of OsPHR4 is positively regulated by OsPHR1, OsPHR2 and OsPHR3. The
      nuclear located OsPHR4 can respectively interact with other three PHR1 subfamily
      members to regulate downstream Pi-starvation induced genes. Consistent with the
      positive role of PHR4 in regulating Pi-starvation signaling, the OsPHR4
      overexpressors display higher Pi accumulation in the shoot and elevated
      expression of Pi-starvation induced genes under Pi-sufficient condition. Besides,
      moderate growth retardation and repression of the Pi-starvation signaling in the
      OsPHR4 RNA interfering (RNAi) transgenic lines can be observed under Pi-deficient
      condition. Together, we propose that OsPHR4 mediates the regulation of Pi
      starvation signaling and Pi-homeostasis in a PHR1-subfamily dependent manner in
      rice.

PMID- 27878662
TI  - A thrombotic storm.

PMID- 27878663
TI  - Prevention and treatment of venous thromboembolism in patients with solid brain
      neoplasms: results of a survey among Italian physicians.
AB  - The decision concerning the introduction of primary and secondary prophylaxis of
      venous thromboembolism (VTE) in patients with solid brain neoplasms and brain
      metastases is often challenging due to the concomitant increased risk of
      intracranial hemorrhage and to limited evidence from available literature. A
      standardized questionnaire composed of nine multiple-choice questions regarding
      primary VTE prevention in non-surgical patients during high-risk conditions and
      VTE secondary prevention in patients with a solid brain neoplasm or cerebral
      metastases was sent via electronic mail to all the members (n = 2420) of the
      Italian Federation of the Internal Medicine Hospital Executives' Associations
      (FADOI) in June 2015. Three hundred and fifty two physicians (14.5%) returned it
      (participants' median age 51 years; females 46.9%). The majority of respondents
      prescribe primary thromboprophylaxis (usually with heparin) in non-surgical
      patients with solid brain neoplasms and brain metastases in concomitance with
      high-risk conditions. Full-dose anticoagulation with either low-molecular-weight
      heparin or fondaparinux is the preferred option for acute VTE (69.6%), while a
      reduced dose is chosen by 21.0% of physicians. The presence of a highly vascular
      brain neoplasm histotype mandates the prescription of a reduced-dose
      antithrombotic regimen in a minority of respondents. Vena cava filter placement
      is an option for the treatment of acute VTE in more than 6% of respondents.
      Anticoagulants are often prescribed for both VTE primary prevention and
      treatment. In conclusion, physicians' managements are partially in contrast to
      recent guidelines, reinforcing the need for educational programs and other
      studies in this setting.

PMID- 27878658
TI  - Role of Matricellular Proteins in Disorders of the Central Nervous System.
AB  - Matricellular proteins (MCPs) are actively expressed non-structural proteins
      present in the extracellular matrix, which rapidly turnover and possess
      regulatory roles, as well as mediate cell-cell interactions. MCPs
      characteristically contain binding sites for other extracellular proteins, cell
      surface receptors, growth factors, cytokines and proteases, that provide
      structural support for surrounding cells. MCPs are present in most organs,
      including brain, and play a major role in cell-cell interactions and tissue
      repair. Among the MCPs found in brain include thrombospondin-1/2, secreted
      protein acidic and rich in cysteine family (SPARC), including Hevin/SC1, Tenascin
      C and CYR61/Connective Tissue Growth Factor/Nov family of proteins, glypicans,
      galectins, plasminogen activator inhibitor (PAI-1), autotaxin, fibulin and
      perisostin. This review summarizes the potential role of MCPs in the pathogenesis
      of major neurological disorders, including Alzheimer's disease, amyotrophic
      lateral sclerosis, ischemia, trauma, hepatic encephalopathy, Down's syndrome,
      autism, multiple sclerosis, brain neoplasms, Parkinson's disease and epilepsy.
      Potential therapeutic opportunities of MCP's for these disorders are also
      considered in this review.

PMID- 27878664
TI  - Diagnosis and management of acquired thrombotic thrombocytopenic purpura in
      southeast China: a single center experience of 60 cases.
AB  - Acquired thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening
      thrombotic microangiopathy. This study aimed to provide a profile of the
      diagnosis and management of patients with acquired TTP collected in 10 years in a
      single center in southeast China. A total of 60 patients diagnosed with acute
      acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients,
      52 patients presented with their first episodes, and eight patients had two or
      more episodes. The median age at presentation was 49 (range, 17 to 78) years with
      a female predominance (male:female ratio, 1:1.60). ADAMTS 13 activity were
      analyzed in 43 patients, among whom 33 (76.7%) patients had a baseline level of <
      5%. Mortality was 30%. Plasma exchange (PEX) was performed in 62 of 69 (89.9%)
      episodes. Corticosteroids were administered in 54 of 69 (78.3%) episodes. Other
      immunosuppressants (e.g., vincristine, cyclosporine, and cyclosporin) were used
      in 7 of 69 (10.1%) episodes. Rituximab was documented in 4 patients with
      refractory/relapsed TTP for 5 episodes, showing encouraging results. In
      conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical
      data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the
      mainstay of the therapy, and rituximab can be used in relapsed/refractory
      disease.

PMID- 27878666
TI  - Have health insurance reforms in Tunisia attained their intended objectives?
AB  - A growing number of developing countries are currently promoting health system
      reforms with the aim of attaining ' universal health coverage' (UHC). In Tunisia,
      several reforms have been undertaken over the last two decades to attain UHC with
      the goals of ensuring financial protection in health and enhancing access to
      healthcare. The first of these goals has recently been addressed in a companion
      paper by Abu-Zaineh et al. (Int J Health Care Financ Econ 13(1):73-93, 2013). The
      present paper seeks to assess whether these reforms have in fact enhanced access
      to healthcare. The average treatment effects of two insurance schemes, formal
      mandatory (MHI) and state-subsidized (MAS) insurance, on the utilization of
      outpatient and inpatient healthcare are estimated using propensity score
      matching. Results support the hypothesis that both schemes (MHI and MAS) increase
      the utilization of healthcare. However, significant variations in the average
      effect of these schemes are observed across services and areas. For all the
      matching methods used and compared with those the excluded from cover, the
      increase in outpatient and inpatient services for the MHI enrollees was at least
      19 and 26 %, respectively, in urban areas, while for MAS beneficiaries this
      increase was even more pronounced (28 and 75 % in the urban areas compared with
      27 and 46 % in the rural areas for outpatient and inpatient services,
      respectively). One important conclusion that emerges is that the current health
      insurance schemes, despite improving accessibility to healthcare services, are
      nevertheless incapable of achieving effective coverage of the whole population
      for all services. Attaining the latter goal requires a strategy that targets the
      "trees" not the "forest".

PMID- 27878665
TI  - Payment schemes and cost efficiency: evidence from Swiss public hospitals.
AB  - This paper aims at analysing the impact of prospective payment schemes on cost
      efficiency of acute care hospitals in Switzerland. We study a panel of 121 public
      hospitals subject to one of four payment schemes. While several hospitals are
      still reimbursed on a per diem basis for the treatment of patients, most face
      flat per-case rates-or mixed schemes, which combine both elements of
      reimbursement. Thus, unlike previous studies, we are able to simultaneously
      analyse and isolate the cost-efficiency effects of different payment schemes. By
      means of stochastic frontier analysis, we first estimate a hospital cost
      frontier. Using the two-stage approach proposed by Battese and Coelli (Empir Econ
      20:325-332, 1995), we then analyse the impact of these payment schemes on the
      cost efficiency of hospitals. Controlling for hospital characteristics, local
      market conditions in the 26 Swiss states (cantons), and a time trend, we show
      that, compared to per diem, hospitals which are reimbursed by flat payment
      schemes perform better in terms of cost efficiency. Our results suggest that
      mixed schemes create incentives for cost containment as well, although to a
      lesser extent. In addition, our findings indicate that cost-efficient hospitals
      are primarily located in cantons with competitive markets, as measured by the
      Herfindahl-Hirschman index in inpatient care. Furthermore, our econometric model
      shows that we obtain biased estimates from frontier analysis if we do not account
      for heteroscedasticity in the inefficiency term.

PMID- 27878667
TI  - Eligibility for free GP care and the utilisation of GP services by children in
      Ireland.
AB  - The majority of the Irish population pay the full out-of-pocket price of a GP
      visit, with only those on low incomes exempt. While there is an extensive
      literature analysing the impact of the Irish system of eligibility for free GP
      care on GP visiting rates among adults, there is a lack of evidence for children.
      Given the importance of socio-economic health inequalities in shaping the future
      outcomes of children, it is important to analyse the extent to which the current
      system of eligibility leads to inequities in access to GP services among Irish
      children. In addition, some private health insurance plans have started to offer
      cover for GP expenses, which adds an additional layer of complexity to the
      existing system of eligibility, and to date, this has not been studied. Using a
      large, nationally-representative data-set covering two cohorts of Irish children
      (9-month olds and 9-year olds), we examine the role of eligibility for free GP
      care in determining GP visiting rates among children. As with the adult
      population, the results show that, even with controls for child health, and
      parental and family characteristics, eligibility for free GP care is a
      significant determinant of GP utilisation among Irish children.

PMID- 27878668
TI  - Effectiveness of micro health insurance on financial protection: Evidence from
      India.
AB  - Iatrogenic poverty caused by inadequate public expenditure on health, lack of
      social health insurance and low penetration of private health insurance can be
      mitigated by micro health insurance (MHI) schemes that provide financial
      protection. The empirical evidence on the impact of MHI on financial protection
      is limited in India. This paper elucidates the effect of Sampoorna Suraksha
      Programme (SSP), a MHI scheme in Karnataka on financial protection. Cross
      sectional study was undertaken in Karnataka and the data was gathered from 416
      insured, 366 newly insured and 364 uninsured households. The impact of SSP on out
      of pocket expenses (OOPE), catastrophic health expenditure (CHE), non-medical
      consumption expenditure, hardship financing and labour supply was analysed using
      linear and logistic regression methods. Results of the study demonstrate that
      insured members incurred lower OOPE, CHE and hardship finance. There was no
      effect on consumption expenditure and no direct impact on labour supply measured
      in terms of withdrawal from workforce and substitution of labour. We advocate a
      larger role of MHI in health financing in India since it curtails impoverishment
      of households in informal sector by reducing OOPE and hardship financing.

PMID- 27878669
TI  - Market power and provider consolidation in physician markets.
AB  - Physician services comprise a substantial share of total health care spending,
      and the price of health care services has been cited as a key contributor to the
      disproportionately high rate of health care spending in the US. However, despite
      a large literature analyzing market power in the hospital and insurance
      industries, less is known about the extent to which physicians exercise market
      power. In this study we make use of a private health insurance claims data set to
      analyze physician market power for two specialties within three mid-sized US
      metropolitan areas. Using a method developed for hospital competition analysis,
      we estimate measures of consumer willingness-to-pay for physician practices
      within each of these markets and relate these to the prices paid to these
      practices for a set of physician services. Our results are suggestive of the
      presence of market power in the markets that we analyze. We simulate physician
      practice mergers for the two largest practices in each market for each specialty
      analyzed. Results suggest that practice mergers could result in price increases
      deemed significant by antitrust authorities in some markets but not in others.

PMID- 27878670
TI  - Editorial: Relaunch of the journal.

PMID- 27878671
TI  - The demand for health care workers post-ACA.
AB  - Concern abounds about whether the health care workforce is sufficient to meet
      changing demands spurred by the Affordable Care Act (ACA). We project that by
      2022 the health care industry needs three to four million additional workers,
      forty percent of which is related to demand growth under the ACA. We project
      faster job growth in the ambulatory care sector, especially in home health care.
      Given the current profile, we expect that the future health care workforce will
      be increasingly female, young, racially/ethnically diverse, not US-born, at or
      below the poverty level and at a low level of educational attainment.

PMID- 27878672
TI  - Public reporting and the evolution of diabetes quality.
AB  - We address three questions related to public reports of diabetes quality. First,
      does clinic quality evolve over time? Second, does the quality of reporting
      clinics converge to a common standard? Third, how persistent are provider quality
      rankings across time? Since current methods of public reporting rely on historic
      data, measures of clinic quality are most informative if relative clinic
      performance is persistent across time. We use data from the Minnesota Community
      Measurement spanning 2007-2012. We employ seemingly-unrelated regression to
      measure quality improvement conditional upon cohort effects and changes in
      quality metrics. Basic autoregressive models are used to measure quality
      persistence. There were striking differences in initial quality across cohorts of
      clinics and early-reporting cohorts maintained higher quality in all years. This
      suggests that consumers can infer, on average, that non-reporting clinics have
      poorer quality than reporting clinics. Average quality, however, improves slowly
      in all cohorts and quality dispersion declines over time both within and across
      cohorts. Relative clinic quality is highly persistent year-to-year, suggesting
      that publicly-reported measures can inform consumers in choice of clinics, even
      though they represent measured quality for a previous time period. Finally,
      definition changes in measures can make it difficult to draw appropriate
      inferences from longitudinal public reports data.

PMID- 27878673
TI  - Reforming the Swedish pharmaceuticals market: consequences for costs per defined
      daily dose.
AB  - In 2009 and 2010, the Swedish pharmaceuticals market was reformed. One of the
      stated policy goals was to achieve low costs for pharmaceutical products
      dispensed in Sweden. We use price and sales data for off-patent brand-name and
      generic pharmaceuticals to estimate a log-linear regression model, allowing us to
      assess how the policy changes affected the cost per defined daily dose. The
      estimated effect is an 18 % cost reduction per defined daily dose at the retail
      level and a 34 % reduction in the prices at the wholesale level (pharmacies'
      purchase prices). The empirical results suggest that the cost reductions were
      caused by the introduction of a price cap, an obligation to dispense the lowest
      cost generic substitute available in the whole Swedish market, and the
      introduction of well-defined exchange groups. The reforms thus reduced the cost
      per defined daily dose for consumers while being advantageous also for the
      pharmacies, who saw their retail margins increase. However, pharmaceutical firms
      supplying off-patent pharmaceuticals experienced a clear reduction in the price
      received for their products.

PMID- 27878674
TI  - Dispensing physicians, asymmetric information supplier-induced demand: evidence
      from the Swiss Health Survey.
AB  - In this paper, we apply a two-part model to estimate the effect of health
      literacy on the demand for physician visits under different institutional
      settings. Using a constructed measure of health information, we find evidence for
      supplier-induced demand in some parts of Switzerland. While the level of health
      information is uncorrelated with the likelihood of visiting a physician (contact
      decision), the conditional number of visits (frequency decision) depends on the
      individual's information status and the regulation of physician drug dispensing.
      In cantons with a drug prescription scheme, we do not find a significant
      difference in the number of visits between well-informed individuals and people
      with relatively little health literacy. In contrast, the existence of self
      dispensing general practitioner and specialists is associated with a gap in
      demand that is strongly related to health literacy: Compared to cantons with
      prescription schemes, uninformed patients exhibit a higher number of outpatient
      visits in the cantons that (partly) allow the dispensation of drugs by
      physicians. However, patients with a high level of health information seem to be
      rather unaffected by physician drug dispensing. As a consequence, we observe an
      information-related gap in the number of outpatient contacts that only prevails
      in areas where doctors are entitled to sell drugs themselves. These findings
      suggest that self-dispensing doctors succeed in inducing demand that affects the
      number of physician-patient contacts. Health literacy, on the other hand, tends
      to counter these incentives.

PMID- 27878675
TI  - Supplementing gatekeeping with a revenue scheme for secondary care providers.
AB  - We study implications of a change in the payment scheme for radiology providers
      in Norway that was implemented in 2008. The change implies reduced fee-for
      service and increased fixed budget for a contracted volume of services. A
      consequence of the change is that private providers have less incentive to
      conduct examinations beyond the contracted volume. Different from the situation
      observed before the change in 2008, the volume is no longer determined by the
      demand side, and a rationing of the supply occurs. We employ data on radiological
      examinations initiated by GPs' referrals. We apply monthly data at the physician
      practice level for 2007-2010. The data set is unique because it includes
      information about all GPs in the Norwegian patient-list system. The results
      indicate that private providers conducted fewer examinations in 2008-2010
      compared with previous periods and that public hospitals did either the same
      volume or more. We find that GPs who operate in a more competitive environment
      experienced a greater reduction in magnetic resonance imaging, both performed by
      private providers and in total for their patients. We argue that this result
      supports a hypothesis that patients with lower expected benefits are rationed.
      Hence, rationing from the supply side might supplement GP gatekeeping.

PMID- 27878676
TI  - Health insurance coverage and self-reported health: new estimates from the
      NLSY97.
AB  - This paper provides new estimates of the relationship between health insurance
      coverage and health status of young adults using the confidential version of the
      National Longitudinal Survey of Youth, 1997 Cohort (NLSY97). Using a regression
      discontinuity design, I find that approximately 6 % of young adults lose their
      health insurance coverage once they turn 19. However, in contrast to the findings
      from the recent literature, the effect of this discrete change in health
      insurance coverage on self-reported health status of young adults is quite
      limited and often statistically insignificant.

PMID- 27878678
TI  - Reference pricing in the presence of pseudo-generics.
AB  - This paper looks at producers of branded and generic pharmaceuticals' pricing
      decisions under two possible reimbursement schemes-reference pricing and fixed
      percentage reimbursement-and under two settings-one where the branded producer
      only sells the (off-patent) branded pharmaceutical and another where, in
      addition, it may also sell its own generic version, a so called pseudo-generic.
      We find different pricing responses from firms under the two reimbursement
      schemes and across the two settings analysed (with or without a pseudo-generic),
      and show that pseudo-generics may have an anticompetitive effect. Our results
      have important policy implications such as showing that the presence of pseudo
      generics reinforces reference pricing's advantages over alternative reimbursement
      schemes.

PMID- 27878677
TI  - Rating the digital help: electronic medical records, software providers, and
      physicians.
AB  - To separate the effects of physicians' characteristics on the perceived
      productivity of EMRs from the effects of limitations on usability inherent in EMR
      design, a multivariate regression model is used to estimate the factors
      influencing physicians' rankings of five attributes of their EMRs, namely; ease
      of use and reliability; the EMRs effect on physician and staff productivity and
      the EMRs performance vs. vendor's promises. We divide the factors influencing the
      rankings into three groups: physician characteristics, EMR characteristics and
      practice characteristics (type of practice, size, and location). The data are
      from approximately 1800 practicing physicians in Arizona. Physician's
      characteristics influence perceived ease of use and physicians' productivity, but
      not staff productivity, reliability or vendors' promised performance. Practice
      type and EMR characteristics affect perceived productivity, reliability and
      performance versus vendors' promises. Vendor-specific effects are highly
      correlated across all five attributes and are always jointly significant. EMR
      characteristics are the most significant influence on physicians' perceptions of
      the EMRs effect on their productivity and that of their staff. Physicians'
      characteristics (particularly age) have a small but significant influence on
      perceived productivity.

PMID- 27878679
TI  - The financial burden of out of pocket prescription drug expenses in Canada.
AB  - Pharmaceutical expenditures account for approximately 15.9 % of total health
      expenditures in Canada. Unlike hospital and physician services, in which costs
      are universally covered, most pharmacological therapy does not fall under the
      umbrella of 'medically necessary' services set out by the Canada Health Act, and
      therefore is funded through a mix of public and private plans. Little is known
      about the actual financial burden experienced by Canadians from out-of-pocket
      drug expenditures (OOPDE). This paper examines the burden of OOPDE in Canada. 1.1
      % of Canadian households exceed our catastrophic threshold (9 %) of the drug
      budget share. Additionally, 2.6 and 8.2 % of households exceed lower thresholds
      of 6 and 3 % respectively. We find an inverse relationship between household
      income and the burden of OPPDE. Low-income households have the highest likelihood
      of being in the 'catastrophic' drug expenditure category. This finding suggests
      that a vulnerable population of 'working poor' are likely to be experiencing
      disproportionate financial burden because they are not eligible for public
      assistance programs. Seniors experience the highest burden of OPPDE when compared
      to other age groups. We also find that there is significant interprovincial
      variation in the burden of OOPDE, which partly reflects different provincial
      government drug coverage policies.

PMID- 27878680
TI  - Catastrophic out-of-pocket payments for health and poverty nexus: evidence from
      Senegal.
AB  - Out-of-pocket payments are the primary source through which health expenditure is
      met in Senegal. However, these payments are financial burdens that lead to
      impoverishment when they become catastrophic. The purpose of this study is to
      cast light on the determinants of catastrophic household out-of-pocket health
      expenditures and to assess their implications on poverty. The 2011 poverty
      monitoring survey is used in this study. This survey aims to draw poverty
      profiles and to highlight the socio-economic characteristics of different social
      groups. In line with the concerns raised by the new Supplemental Poverty Measure,
      poverty statistics are adjusted to take into account household health
      expenditures and to estimate their impoverishing effects. To identify the
      determinants of the magnitude of catastrophic health expenditure, we implement a
      seemingly unrelated equations system of Tobit regressions to take into account
      censoring through a conditional mixed-process estimator procedure. We identify
      major causes of catastrophic expenditures, such as the level of overall health
      spending, the expensiveness of health goods and services, the characteristics of
      health facilities, the health stock shocks, the lack of insurance, etc. Results
      show evidence that catastrophic health expenditures jeopardize household welfare
      for some people that fall into poverty as a result of negative effects on
      disposable income and disruption of the material living standards of households.
      Our findings warrant further policy improvements to minimize the financial risks
      of out-of-pocket health expenditures and increase the efficiency of health care
      system for more effective poverty reduction strategies.

PMID- 27878681
TI  - The impact of pharmaceutical innovation on premature cancer mortality in Canada,
      2000-2011.
AB  - The premature cancer mortality rate has been declining in Canada, but there has
      been considerable variation in the rate of decline across cancer sites. I analyze
      the effect that pharmaceutical innovation had on premature cancer mortality in
      Canada during the period 2000-2011, by investigating whether the cancer sites
      that experienced more pharmaceutical innovation had larger declines in the
      premature mortality rate, controlling for changes in the incidence rate.
      Premature mortality before age 75 is significantly inversely related to the
      cumulative number of drugs registered at least 10 years earlier. Since mean
      utilization of drugs that have been marketed for less than 10 years is only one
      sixth as great as mean utilization of drugs that have been marketed for at least
      a decade, it is not surprising that premature mortality is strongly inversely
      related only to the cumulative number of drugs that had been registered at least
      ten years earlier. Premature mortality before age 65 and 55 is also strongly
      inversely related to the cumulative number of drugs that had been registered at
      least ten years earlier. None of the estimates of the effect of incidence on
      mortality are statistically significant. Controlling for the cumulative number of
      drugs, the cumulative number of chemical subgroups does not have a statistically
      significant effect on premature mortality. This suggests that drugs (chemical
      substances) within the same class (chemical subgroup) are not therapeutically
      equivalent. During the period 2000-2011, the premature (before age 75) cancer
      mortality rate declined by about 9 %. The estimates imply that, in the absence of
      pharmaceutical innovation during the period 1985-1996, the premature cancer
      mortality rate would have increased about 12 % during the period 2000-2011. A
      substantial decline in the "competing risk" of death from cardiovascular disease
      could account for this. The estimates imply that pharmaceutical innovation during
      the period 1985-1996 reduced the number of years of potential life lost to cancer
      before age 75 in 2011 by 105,366. The cost per life-year before age 75 gained
      from previous pharmaceutical innovation is estimated to have been 2730 USD. Most
      of the previously-registered drugs were off-patent by 2011, but evidence suggests
      that, even if these drugs had been sold at branded rather than generic prices,
      the cost per life-year gained would have been below 11,000 USD, a figure well
      below even the lowest estimates of the value of a life-year gained. The largest
      reductions in premature mortality occur at least a decade after drugs are
      registered, when their utilization increases significantly. This suggests that,
      if Canada is to obtain substantial additional reductions in premature cancer
      mortality in the future (a decade or more from now) at a modest cost,
      pharmaceutical innovation (registration of new drugs) is needed today.

PMID- 27878682
TI  - DFT study on the effects of beta-cyclodextrin in synthesis of 2
      phenylbenzimidazole via benzaldehyde and o-phenylenediamine.
AB  - The conversion of 2-phenylbenzimidazole using o-phenylenediamine and benzaldehyde
      can be improved significantly under beta-cyclodextrin (beta-CD). The density
      functional theory (DFT) method was applied to study the whole process. According
      to energy parameters (binding energy, deformation energy) and structural
      deformation, entry models and the reaction process can be pinpointed, with o
      phenylenediamine embedding beta-CD from a wide rim, and then benzaldehyde passing
      into the inclusion from the narrow rim. Subsequently, natural bonding orbital
      (NBO), Mulliken charge, frontier orbital, FuKui function and nuclear magnetic
      resonance (NMR) methods were employed to reveal the mechanism of electron
      transfer. The results illustrate that beta-CD plays a catalytic role in synthesis
      reaction mechanism on the secondary side, improving the reactivity and
      selectivity of the process. Graphical Abstract Density functional theory study of
      the effects of beta-cyclodextrin in synthesis of 2-phenylbenzimidazole via
      benzaldehyde and o-phenylenediamine.

PMID- 27878683
TI  - APRIL gene polymorphism and serum sAPRIL levels in children with systemic lupus
      erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multi-factor autoimmune disorder with
      diverse clinical manifestations and unclear pathogenesis. Genetic components play
      important roles in the incidence and development of SLE. Among these, APRIL as a
      cytokine has roles in the stimulation and antibody production in B cells. APRIL
      was hypothesized to be associated with SLE. The aim of this study was to assess
      the involvement of the APRIL gene in SLE susceptibility in Iranian patients. A
      single-nucleotide polymorphism (SNP) for rs11552708 of APRIL gene was analyzed by
      real-time PCR in 60 SLE Iranian children and 64 healthy controls. DNA samples of
      patients and healthy controls were extracted from peripheral blood leukocytes by
      phenol-chloroform. Serum samples obtained from 45 children with SLE and 45
      healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). The
      G/G genotype (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.22-2.07; P =
      0.68) and G allele (OR 0.81, 95% CI 0.25-2.56; P = 0.89) frequencies of
      polymorphism at codon 67 (67G) do not differ significantly in the SLE patients
      compared with those in the healthy controls. The serum APRIL levels in the SLE
      patients (mean +/- SD = 29.27 ng/ml +/- 20.77, range from 0 to 55.33 ng/ml) were
      significantly higher than those in the healthy controls (P = 0.02). Our results
      demonstrated that rs11552708 of the APRIL gene is not associated with SLE
      susceptibility in Iranian children. Likewise, these findings suggest that APRIL
      antagonist could be a potential therapeutic target to control SLE in children.

PMID- 27878684
TI  - Bakuchiol Protects Against Acute Lung Injury in Septic Mice.
AB  - Sepsis is a systemic inflammatory reaction that may lead to multiple organ damage
      and acute lung injury (ALI). Bakuchiol (Bak) has been reported to confer
      protection against inflammation and oxidative stress. However, its effect on
      sepsis-induced acute lung injury remains unclear. In the present study, male
      C57BL/6 mice were subjected to cecal ligation and puncture (CLP), and Bak (15,
      30, 60 mg/kg) was administered intragastrically after 0 and 3 h of surgery. Lung
      water content was detected. Pathologic changes in lung tissues were evaluated via
      hematoxylin and eosin (H&E) staining. The levels of myeloperoxidase (MPO), IL
      1beta, IL-6, and TNF-alpha were evaluated using ELISA. In addition, expression
      levels of phosphorylated (p)-IkappaB, ICAM-1, HMGB1, nitrotyrosine (3-NT),
      claudin-1, and VE-cadherin were detected using Western blot. Further, IL-1beta
      expression was evaluated using immunofluorescence. SOD activity, contents of MDA,
      and 8-OHdG were detected to determine the level of oxidative stress. Our results
      suggested that Bak (60 mg/kg) treatment significantly attenuated pathologic
      changes and edema in lung tissues and attenuated inflammation and oxidative
      stress in the lung following sepsis. Additionally, Bak treatment alleviated
      sepsis-induced lung endothelial barrier disruption. In conclusion, Bak treatment
      attenuates ALI following sepsis by suppressing inflammation, oxidative stress,
      and endothelial barrier disruption. Our study indicates that Bak is a potential
      candidate to treat sepsis-induced ALI.

PMID- 27878685
TI  - The Role of IL-33 on LPS-Induced Acute Lung Injury in Mice.
AB  - The objective of the study is to investigate the role and specific molecular
      mechanism of interleukin-33 (IL-33) acted on acute lung injury (ALI) induced by
      lipopolysaccharide (LPS). C57BL/6 mice intratracheally instilled LPS to induce
      ALI model. The mice were randomly divided into three groups: the sham operation
      group (Sham), ALI group (ALI), and pretreatment with IL-33 of ALI group (IL-33).
      By observing the survival rate, inflammatory cytokines in bronchoalveolar lavage
      fluid (BALF), myeloperoxidase (MPO) levels in lung tissue, lung histopathological
      examination, pulmonary capillary leakage, lung wet/dry (W/D) weight ratio,
      fibrosis levels in lung tissue, and associated pathways changes among the
      different groups, comparing to explore the role of IL-33 pretreatment on ALI mice
      and the possible molecular mechanisms. IL-33 pretreatment overall decreased the
      survival rate of ALI mice. IL-33 aggravated inflammation reaction showing as
      increasing the release of proinflammatory cytokines TNF-alpha and IL-6,
      increasing MPO levels in lung tissue, and aggravating lung pathology injury. In
      addition, IL-33 pretreatment further destroyed adherens junctions (AJs) by
      increasing the phosphorylation of VE-cadherin, resulting in the concomitantly
      pulmonary capillary barrier damage and pulmonary edema. During this process,
      mitogen-activated protein kinase (MAPK) pathways further activated. However, IL
      33 pretreatment had no significant impact on collagen content of lung tissue. Our
      results indicated that IL-33 aggravated inflammatory reaction and increased
      microvascular permeability, but had little effect on pulmonary fibrosis,
      associated with the further activation of MAPK family proteins in the process. To
      sum up, IL-33 decreased survival rate and aggravated LPS-induced ALI.

PMID- 27878686
TI  - Role of Anti-inflammatory Cytokines IL-35 and IL-37 in Asthma.
AB  - Asthma is a chronic airway inflammation that is characterized by intense
      eosinophil infiltrates, mucus hypersecretion, airway remodeling, and airway
      hyperresponsiveness. Interleukin (IL)-35 and IL-37 are two cytokines with anti
      inflammatory effects found in immune response. Recent findings suggested that
      expressions of IL-35 and IL-37 are abnormal in asthma. Functional analysis
      further confirmed the important roles of them in the pathogenesis of asthma. The
      present study reviewed the updated evidence indicating the roles of IL-35 and IL
      37 in asthma. Hopefully, the information obtained may lead to a better
      understanding of the pathogenesis of the disease.

PMID- 27878688
TI  - Outpatient visits after retirement in Europe and the US.
AB  - I conduct an empirical analysis of the relation between retirement and outpatient
      care use in Europe and the US, and investigate the potential driving factors of
      that. I link the empirical analysis to a theoretical model of medical care
      demand. I document that pensioners tend to visit a doctor with higher probability
      and more often than the rest of the 50+ population. Ceteris paribus, being
      retired implies 3-10 % more outpatient visits in Europe. The estimates are of
      similar magnitude in the US. The paper contributes to the understanding of how
      population ageing plays a part in the rising health care expenditures. I find
      evidence that retirement related individual characteristics, increasing leisure
      time and stronger health preferences all contribute to the positive relation
      between retirement and outpatient care use, which is mainly driven by the
      healthier individuals. The gatekeeper role of general practitioners can mitigate
      the increased demand for outpatient care services after retirement.

PMID- 27878689
TI  - For-profit status and industry evolution in health care markets: evidence from
      the dialysis industry.
AB  - This paper examines why for-profit dialysis providers have displaced non-profit
      providers over the last 25 years. Using detailed data on individual markets'
      evolutions, I find that for-profit facilities were quicker to enter growing
      markets and slower to exit declining ones than non-profit facilities. Moreover,
      for-profit providers' presence in a market had a larger impact on the exit and
      entry behavior of competitors. These results suggest that for-profit dialysis
      providers have an advantage in static competition relative to non-profit
      providers, and that this-rather than lower entry costs-explains their increasing
      prominence. Additional empirical analyses indicate that for-profits' advantage
      cannot solely be attributed to efficiencies related to membership in a large,
      multi-facility chain. This further suggests that managerial incentives have had
      an economically significant impact on long-run market structure in this industry.

PMID- 27878687
TI  - Aptamers Against Pro- and Anti-Inflammatory Cytokines: A Review.
AB  - Inflammatory disorders result from continuous inflammation in injured sites. Many
      molecules are involved in this process; the inhibition of which could prevent the
      inflammation. Chemokines are a group of these biological mediators which are
      categorized into pro-, anti-, and pro-/anti-inflammatory. Thus, targeting these
      essential molecules can be an effective way for prevention and control of
      inflammatory diseases. Various therapeutic agents have been developed for primary
      and secondary prevention of these disorders, but each of them has its own
      limitations. Aptamers, as novel therapeutic agents, are a new generation of drugs
      which could replace other medications even antibodies. Aptamer can bind to its
      target molecule to trap it and prohibit its function. Among large group of
      inflammatory cytokines, only 11 aptamers have been selected either against
      cytokines or their related receptors. These cytokines include interleukin (IL)-2,
      IL-6, IL-10, IL-11, IL-17, IL-32, TGF-beta, TNF-alpha, IFN-gamma, CCL2, and IP
      10. Most of the isolated aptamers are against pro-inflammatory or dual function
      cytokines, and it seems that they could be used for diagnosis, prevention, and
      treatment of the related inflammatory diseases. Most of the aptamers have been
      tested in vitro, but so far, none of them has been approved for in vivo use.
      Given a vast number of inflammatory cytokines, more aptamers against this group
      of biological molecules will be selected in the near future. The available
      aptamers will also be tested in clinical trials. Therefore, a significant
      improvement is expected for the prevention and control of inflammatory disorders.

PMID- 27878690
TI  - Willingness to pay and the sensitivity of willingness to pay for
      interdisciplinary musculoskeletal clinics: a contingent valuation study in
      Quebec, Canada.
AB  - Orthopedics is a discipline that requires a continuum of care in close
      collaboration with physicians, nurses, and healthcare professionals to ensure
      effective rehabilitation. In some cases, the wait time for a consultation may be
      very long, which can jeopardize the patient's rehabilitation and sometimes even
      cause complications that lead to a loss of autonomy. In Quebec, there is a severe
      shortage of healthcare professionals-and of orthopedic surgeons, in particular
      specializing in musculoskeletal problems. To address this problem, public
      managers have decided to establish interdisciplinary musculoskeletal clinics in
      regions outside the two major cities of Montreal and Quebec. The major benefits
      of these clinics are that they reduce the wait time for consultation and
      treatment while maintaining service quality. Although their benefits are certain,
      these clinics remain threatened by relatively high initial costs. This study's
      objective is to evaluate whether the population of Quebec has a quantifiable
      willingness to pay (WTP) to establish these clinics. To our knowledge, this is
      the first study of its kind either in the province of Quebec or elsewhere. We
      selected 3822 subjects randomly within the target population using Internet
      surveys, telephone surveys and self-administered paper surveys as our methods of
      recruitment. Three payment vehicles were used and each participant was randomly
      allocated among these: tax, donation or lump-sum fee. A contingent valuation
      question using a referendum format with the option "don't know" was used.
      Econometric estimates were performed using probit and Wang's models. Our results
      indicate that the population of Quebec may potentially have a mean WTP of 42.3
      Canadian dollars per person for such clinics, which would enable a mean reduction
      from 12 to 4 months of wait time. However, the WTP is found to be very sensitive
      to the survey mode and the payment vehicle used: about 1.2-2 times more important
      in the tax and the lump-sum fee scenarios than in the donation scenario, and
      about 3-4 times less important in the Internet survey than in the telephone or
      self-administered paper surveys. In addition, this amount was strongly affected
      by the introduction of a new governmental health-related policy that arose during
      the survey and led to a minimal drop in WTP of about 30-50 %. This strong
      sensitivity led us to the three following recommendations for future contingent
      valuation studies: (1) favour Internet surveys, (2) use a payment vehicle that
      limit uncertainty in the WTP answer and allow to socialize benefits, as the tax
      scenario in our study, and (3) strictly apply the "divide by 2" rule of the NOAA
      panel.

PMID- 27878691
TI  - Can patent duration hinder medical innovation.
AB  - We argue that, in the pharmaceutical industry, excessive patent duration can
      deter investments in innovative treatments in favor of me-too drugs. The point is
      that too-long durations foster incentives to collude to delay investments in R&D
      for innovative treatments. We give a set of sufficient conditions for which
      collusion is a subgame-perfect equilibrium; that is, the threat of punishing any
      deviator is credible. We then show that reducing current duration always breaks
      down market discipline, and so does an increase in duration for innovative
      treatments. Optimal patent duration must then be a trade-off between breaking
      down market discipline and rewarding innovation.

PMID- 27878692
TI  - Medical employment growth, unemployment, and the opportunity cost of health care.
AB  - This policy note examines the relationship between the growth in the share of the
      workforce in medical care and the shares of workers who are unemployed, working
      in services or government employment, or working elsewhere in the economy. These
      changes provide measures of the opportunity cost of higher medical care spending,
      the majority of which is on labor. Using state data over the period 1990-2010, we
      find that, in years of high economy-wide unemployment, growth in medical
      employment in a state reduces the unemployment rate significantly; it does not
      appear to displace employment in other services or government employment. In
      periods of low economy wide-unemployment, the growth in the medical employment
      share does not reduce unemployment. We argue that the opportunity cost of higher
      medical care employment may sometimes not be so high in terms of real labor
      resources, nor in terms of employment for needed government services.

PMID- 27878693
TI  - Is medicines parallel trade 'regulatory arbitrage'?
AB  - Parallel trade (PT) is a phenomenon that takes place at the distribution level,
      when a patented product is diverted from the official distribution chain to
      another one where it competes as a parallel distributor. Although some research
      regards PT in Europe as a 'common' form of arbitrage, there are reasons to
      believe that it is a type of 'regulatory arbitrage' that does not necessarily
      produce equivalent welfare effects. We draw upon a unique dataset that contains
      source country records of parallel imported medicine sales to the Netherlands for
      one therapeutic group (statins), that accounts for 5 % of the market at the time
      of study and it faced no generic competition. We estimate precise differences in
      prices and statutory distribution margins for each source country/product and,
      examine whether they drive parallel import flows using a gravity specification
      and an instrumental variable strategy. Our findings reveal that parallel imports
      are driven by cross-country differences in statutory distribution margins in
      addition to price differences, consistently with the hypothesis of PT being a
      type of 'regulatory arbitrage'.

PMID- 27878694
TI  - Physical activity and time preference.
AB  - This paper investigates the link between time preference (whether a person is
      more present or future oriented) and time spent participating in physical
      activity. Using data on time spent engaged in physical activity from the National
      Longitudinal Surveys of Youth 1979 cohort, 2006 wave, where time preference is
      proxied by the expected share of money saved from a hypothetical $1000 cash
      prize. I find that time preference is a significant predictor of the amount of
      time spent participating in both vigorous and light-to-moderate physical activity
      for women and vigorous physical activity for men. The results are robust to
      various sample restrictions and alternative measures of time preference. The
      findings in this paper fill in a gap in the relationship between time preference
      and body composition by examining one of the pathways through which the former
      might affect the latter using a large, nationally representative dataset.

PMID- 27878695
TI  - Medical expenditure in urban China: a quantile regression analysis.
AB  - Many countries have been trying to expand their public health insurance coverage
      in recent years. To achieve two fundamental policy goals-equity in health care
      utilization and control of health care costs-policymakers need a better
      understanding of the underlying determinants of individual health care
      expenditure beyond the results of mean regressions. In this paper, we apply a
      quantile regression method to investigate the heterogeneous effects of various
      determinants of medical expenditure in China. Comparing with the average effects,
      we find that health care expenditures at the upper end of the distribution are
      under stronger influences of need factors such as poor health status, and weaker
      influences of socioeconomic factors and insurance status. On the other hand,
      health care expenditures at the lower end of the distribution are under stronger
      influences of socioeconomic factors and insurance status, and weaker influences
      of need factors. Our study may provide useful information to policymakers for the
      optimal design of their health care systems, and it may be of particular
      interests to the health policymakers in China, where is currently still in a
      period of reshaping its health-care system.

PMID- 27878696
TI  - Under regional characteristics of rural China: a clearer view on the performance
      of the New Rural Cooperative Medical Scheme.
AB  - The New Cooperative Medical Scheme (NCMS) was implemented in 2003 in response to
      the poor state of health care in rural China. Considering the substantial
      differences in regional socioeconomics, preferences for health care needs, and
      concurrent implementation of other health-related policies, the extent to which
      the impact of the NCMS differs in rural communities across China is unclear. The
      objective of this paper, therefore, was to explore the variation in the
      determinants of household enrolment and the impact of enrolment on health care
      utilization and medical expenditures in three large geographic regions in China.
      A quasi-experiment study was designed based on the panel data of the China Health
      and Nutrition Survey. The bounding approach was used to conduct a robust check of
      impact estimation under the assumption of unobserved bias. A major finding is
      that household income plays no significant role for enrolment, which indicates
      the equity of program coverage in income terms. However, regional circumstances
      matter. In the generally poorer western regions, households with a high ratio of
      migrant workers are less attracted to the NCMS program, and adoption of the
      program is related to the regional infrastructure environment variables in the
      eastern and western regions. The NCMS has improved medical care utilization for
      poor income groups and regions (western regions). The NCMS's impact on reducing
      the incidence of catastrophic expenditures is not shown for all regions.

PMID- 27878697
TI  - NFkappaBP65 transcription factor modulates resistance to doxorubicin through ABC
      transporters in breast cancer.
AB  - BACKGROUND: Shedding light on chemoresistance biology of breast cancer could
      contribute to enhance the clinical outcome. Intrinsic or acquired resistance to
      chemotherapy is a major problem in breast cancer treatment. METHODS AND
      MATERIALS: The NFkappaB pathway by siRNAP65 and JSH-23 as a translocational
      inhibitor of NFkappaBP65 in the doxorubicin-resistant MCF-7 (MCF-7/Dox) and MCF-7
      cells was blocked. Then, the ABC transporter expression and function were
      assessed by real-time qRT-PCR and flow cytometry, respectively. Induction of
      apoptosis was evaluated after inhibition of the NFKappaB pathway as well.
      RESULTS: Our study underlined the upregulation of NFkappaBP65 and anti-apoptotic
      Bcl-2 and downregulation of pro-apoptotic Bax in the MCF-7/Dox cells compared
      with control MCF-7 cells. Here, we showed that interplay between nuclear factor
      kappa B P65 (NFkBP65) as a transcriptional regulator and ABC transporters in the
      MCF-7/Dox cancer cells. We found that inhibition of the elevated expression of
      NFkappaBP65 in the resistant breast cancer, whether translocational inhibition or
      silencing by siRNA, decreased the expression and function of MDR1 and MRP1 efflux
      pumps. Furthermore, the blockade of NFkappaBP65 promoted apoptosis via modulating
      Bcl-2 and BAX expression. After inhibition of the NFkappaBP65 signaling pathway,
      elevated baseline expression of survival Bcl-2 gene in the resistant breast cells
      significantly decreased. CONCLUSION: Suppression of the NFkappaB pathway has a
      profound dual impact on promoting the intrinsic apoptotic pathway and reducing
      ABC transporter function and expression, which are some of the chemoresistance
      features. It was speculated that the NFkappaB pathway directly acts on
      doxorubicin-induced MDR1 and MRP1 expression in MCF-7/Dox cells.

PMID- 27878698
TI  - Mitral valve enhancement in a patient with active Rheumatic Fever: An uncommon
      phenomenon on the MRI examination with possible clinical significance.
AB  - Intense enhancement of the mitral valve is documented in a MRI examination
      performed on a patient with rheumatic multi-valvular disease. Patient had the
      elevated inflammatory markers indicating active inflammatory process. Such
      hitherto undocumented phenomenon may have important clinical significance in
      disease evaluation, thus provide a feasible option to document and follow up,
      active valvular involvement in patients with active rheumatic fever.

PMID- 27878699
TI  - Differentiation of light-chain cardiac amyloidosis from hypertrophic
      cardiomyopathy using myocardial mechanical parameters by velocity vector imaging
      echocardiography.
AB  - We aimed to evaluate the diagnostic efficacy of layered velocity vector imaging
      (VVI)-derived left ventricular (LV) mechanical parameters in the differential
      diagnosis of primary light-chain cardiac amyloidosis (AL-CA) and hypertrophic
      cardiomyopathy (HCM). We recruited 35 subjects with histologically-diagnosed AL
      CA, 35 subjects with HCM, and 30 age-matched healthy controls. We used
      conventional echocardiography and electrocardiogram to evaluate general heart
      function and electrophysiology properties. Furthermore, we applied two
      dimensional VVI echocardiography to assess the layered mechanical parameters
      during systole, including endocardial and epicardial longitudinal strain (ENDO
      and EPI LSsys), circumferential strain (CSsys), radial strain (RSsys), rotation
      (ROT) and twist (TWI), in different LV walls and levels. Two groups of patients
      had similarly elevated LV wall thickness and mild diastolic dysfunction, but
      normal ejection fraction. ENDO LSsys of three circular LV levels and six LV walls
      was markedly decreased in AL-CA patients, with the most prominent reduction in
      the basal level. The reduction of ENDO and EPI LSsys in HCM subjects was less
      profound, and was restricted to certain LV wall and levels. AL-CA patients had
      significantly reduced RSsys in the LV basal level compared with control or HCM
      patients. Two groups of patients exhibited similar reduction in layered regional
      CSsys, ROT and TWI. ROC analysis revealed that the sensitivity and specificity of
      basal ENDO LSsys for predicting AL-CA was 86 and 89%. Assessment of layered LSsys
      of LV walls and levels by VVI appeared to provide a more sensitive and specific
      diagnostic index for the differential diagnosis of AL-CA from HCM than
      conventional echocardiography. Future studies are warranted to evaluate its
      diagnostic efficacy for AL-CA diagnosis in the large population.

PMID- 27878701
TI  - Physicians' balance billing, supplemental insurance and access to health care.
AB  - Some countries allow physicians to balance bill patients, that is, to bill a fee
      above the one that is negotiated with, and reimbursed by the health authorities.
      Balance billing is known for restricting access to physicians' services while
      supplemental insurance against balance billing amounts is supposed to alleviate
      the access problem. This paper analyzes in a theoretical setting the consequences
      of balance billing on the fees setting and on the inequality of access among the
      users of physicians' services. It also shows that supplemental insurance against
      the expenses associated with balance billing, rather than alleviating the access
      problem, increases it.

PMID- 27878700
TI  - Performance of native and contrast-enhanced T1 mapping to detect myocardial
      damage in patients with suspected myocarditis: a head-to-head comparison of
      different cardiovascular magnetic resonance techniques.
AB  - Myocardial T1 mapping is a novel technique that has proven to be superior to
      standard imaging for differentiation between healthy individuals in acute
      myocarditis. Aim of this study was comparison of T1 mapping with a clinical
      biomarker. We retrospectively investigated 171 patients undergoing cardiovascular
      magnetic resonance (CMR) examination with suspected myocarditis by performing
      native and contrast enhanced T1-mapping. Additionally, T2w and T1w images and
      late gadolinium enhancement sequences (LGE) were utilized for myocardial
      evaluation; Lake Louise Criteria comprise T1w, T2w and LGE imaging in a score.
      Reference for positive myocarditis diagnosis was a ten-fold increase of troponin
      level above normal (0.14 ng/ml). Native T1 and extracellular volume (ECV) showed
      good association with relevant troponin elevations. Area under the curve (AUC)
      was 81% (p = 0.0001) for native T1 with an optimal threshold of 979 ms and 86% (p
      < 0.0001) for ECV with an optimal cutoff of 32.4%. AUC for T2w imaging (T2-signal
      intensity ratio to skeletal muscle) was 77% (p = 0.0003). AUC for T2w imaging (T2
      signal intensity compared to remote myocardium) was 69% (p = 0.012).
      Additionally, we found positive correlation for native T1 and ECV with the Lake
      Louise Criteria (r = 0.44, p = 0.0001 for native T1 and r = 0.45, p = 0.0001 for
      ECV). Correlated to troponin as biomarker, ECV and native T1 mapping perform at
      least equally well in comparison to established CMR-techniques LGE, T2w imaging
      and the combined Lake Louise Criteria in detecting acute myocardial damage.
      Normal ECV values rule out myocardial damage with very high certainty. T1 mapping
      qualifies for further prospective evaluations to evolve as a separate biomarker.

PMID- 27878702
TI  - Unmet needs in formal care: kindling the spark for caregiving behavior.
AB  - This paper studies if a situation of formal care unmet needs is a strong
      motivation for the onset of caregiving behavior, and if becoming caregiving is a
      compelling argument for leaving current job (in the presence/absence of formal
      care unmet needs). We use data from the Eurobarometer 67.3 for 18 European
      countries and estimate a three simultaneous equations model taking into account
      the potential endogeneity of labor participation and formal care unmet needs and
      assuming non-zero correlation among the error terms of the three equations.
      Results show that individuals who anticipate that becoming caregiver can suppose
      an obstacle for continuing working feel more refractory and are more prone to
      avoid caregiving responsibilities. Knowing someone with an unmet needs problem
      increases the probability of becoming caregiver by +19.23 pp (with a maximum of
      +39.39 pp for difficult access unmet needs) and raises the probability of leaving
      employment by 5.77 pp. Having to possibility of receiving economic benefits for
      caregivers encourage more labor market exit as compared to payment of social
      security contributions during care leaves.

PMID- 27878704
TI  - The effect of physician remuneration on regional variation in hospital
      treatments.
AB  - We study medical practice variations for nine hospital treatments in the
      Netherlands. Our panel data estimations include various control factors and
      physician's role to explain hospital treatments in about 3,000 Dutch zip code
      regions over the period 2006-2009. In particular, we exploit the physicians'
      remuneration difference-fee-for-service (FFS) versus salary-to explain the effect
      of financial incentives on medical production. We find that utilization rates are
      higher in geographical areas where more patients are treated by physicians that
      are paid FFS. This effect is strong for supply sensitive treatments, such as
      cataracts and tonsillectomies, while we do not find an effect for non-supply
      sensitive treatments, such as hip fractures.

PMID- 27878703
TI  - Can universal access and competition in long-term care insurance be combined?
AB  - In countries with a public long-term care (LTC) insurance scheme administered by
      multiple non-competing insurers, these insurers typically lack incentives for
      purchasing cost-effective LTC because they are not at risk for LTC expenses.
      Plans to introduce these incentives by allowing competition among risk bearing
      LTC insurers are likely to jeopardize universal access. Combining universal
      access and competition among risk bearing LTC-insurers requires an adequate
      system of risk adjustment. While risk adjustment is now widely adopted in health
      insurance, LTC-specific features cause uncertainty about the feasibility of risk
      adjustment for LTC insurance. We examine the feasibility of appropriate risk
      adjustment in LTC insurance by using a rich set of linked nationwide Dutch
      administrative data. As expected, prior LTC use and demographic information are
      found to explain much of the variation in individual LTC expenses. However, we
      find that prior health care expenditures are also important in reducing predicted
      losses for subgroups of health care users. Nevertheless, incentives for risk
      selection against some easily identifiable subgroups persist. Moreover, using
      prior utilization and expenditure as risk adjusters reduces incentives for
      efficiency, creating a trade-off between equity and efficiency. To ease this
      trade-off, data on individuals' underlying needs for LTC are required.

PMID- 27878705
TI  - Do preferences of drinker-drivers differ?
AB  - Why people engage in illegal activities is not well understood. Using data
      collected for this research from eight cities in four states, this study
      investigates alternative explanations as to why people drive while intoxicated
      (DWI). We find that preferences and subjective beliefs about arrest/incarceration
      of persons who drink and drive do differ systematically from others in terms of
      benefits and costs of drink and driving, and in their risk tolerance. While most
      findings imply that DWI is a deliberate choice, we do find that drinker drivers
      tend to be more impulsive and lack self-control in their drinking.

PMID- 27878706
TI  - The effect of health care expenditures on self-rated health status and the Health
      Utility Index: Evidence from Canada.
AB  - Studies of the effect of health care expenditures on health status suggest
      conflicting evidence of a relationship using data from numerous countries. We use
      data from the Canadian National Population Health Survey and the Canadian
      Institute for Health Information to estimate the relationship between per capita
      provincial health care expenditures and both self-assessed health status and the
      Health Utility Index. Our sample includes all individuals who were 18 years old
      or over at the beginning of the survey in 1994. We use random effects ordered
      probits for self-assessed health status and quantile regressions for the Health
      Utility Index (HUI). Our results show that provincial health care expenditures
      have a limited effect on self-rated health status and the HUI. It may be that
      self-rated health status and the HUI are noisy measures of heath status and as
      such, combined with the small variation observed in health care expenditure
      trends over the period, make the magnitude of the relationship between health
      care expenditures and health difficult to estimate.

PMID- 27878707
TI  - Local house prices and mental health.
AB  - This paper examines the impact of local (county-level) house prices on individual
      self-reported mental health using individual level data from the United States
      Behavioral Risk Factor Surveillance System between 2005 and 2011. Exploiting a
      fixed-effects model that relies on within-county variations, relative to the
      corresponding changes in other counties, I find that while individuals are likely
      to experience worse self-reported mental health when local house prices decline,
      this association is most pronounced for individuals who are least likely to be
      homeowners. This finding is not consistent with a prediction from a pure wealth
      mechanism but rather with the hypothesis that house prices act as an economic
      barometer. I also demonstrate that the association between self-reported mental
      health and local house prices is not driven by unemployment or foreclosure. The
      primary result-that lower local house prices have adverse impact on self-reported
      mental health of homeowners and renters-is consistent with studies using data
      from the United Kingdom.

PMID- 27878708
TI  - The U.S. health production function: evidence from 2001 to 2009.
AB  - This study estimates the impact of the 2007 financial crisis upon U.S. health as
      measured by age adjusted death rates. OLS regression results suggest that the
      average death rate was lower in the post-crisis period than the pre-crisis
      period. The majority of the average decline in the death rate was a result of the
      time period and not a result of changes in the values of the underlying
      explanatory variables. We continue to find this result even adding state fixed
      effects. Contrary to other research, we find that the unemployment rate has no
      statistically significant impact on death rates either for the U.S. as a whole or
      for any states individually. Rather, the impact of the financial crisis is felt
      via year fixed effects that increased over time during the post-crisis period.

PMID- 27878709
TI  - Is income relevant for health expenditure and economic growth nexus?
AB  - This paper examines the relationship between health expenditure and economic
      growth using panel data consisting low and high-income countries. Using dynamic
      panel data methodology, we analyze twenty five high-income and nineteen low
      income economies for the periods of 1995-2012 and 1997-2009, respectively. We
      find reciprocal relationship between health expenditure and economic growth in
      the short run and one-way causality from economic growth to public health
      expenditure in the long-run. In high-income countries, there is a two-way
      causality for both private and public health expenditures in the short-run, while
      in the long-run there is a one-way causality between economic growth and private
      health expenditures. The crucial finding of this study is that private health
      expenditures have negative influence on economic growth while public health
      expenditures have both negative and statistically significant effect.

PMID- 27878710
TI  - The differential effect of compensation structures on the likelihood that firms
      accept new patients by insurance type.
AB  - Adequate access to primary care is not universally achieved in many countries,
      including the United States, particularly for vulnerable populations. In this
      paper we use multiple years of the U.S.-based Community Tracking Survey to
      examine whether a variety of physician compensation structures chosen by
      practices influence the likelihood that the practice takes new patients from a
      variety of different types of insurance. Specifically, we examine the roles of
      customer satisfaction and quality measures on the one hand, and individual
      physician productivity measures on the other hand, in determining whether or not
      firms are more likely to accept patients who have private insurance, Medicare, or
      Medicaid. In the United States these different types of insurance mechanisms
      cover populations with different levels of vulnerability. Medicare (elderly and
      disabled individuals) and Medicaid (low income households) enrollees commonly
      have lower ability to pay any cost sharing associated with care, are more likely
      to have multiple comorbidities (and so be more costly to treat), and may be more
      sensitive to poor access. Further, these two insurers also generally reimburse
      less generously than private payors. Thus, if lower reimbursements interact with
      compensation mechanisms to discourage physician practices from accepting new
      patients, highly vulnerable populations may be at even greater risk than
      generally appreciated. We control for the potential endogeneity of incentive
      choice using a multi-level propensity score method. We find that the compensation
      incentives chosen by practices are statistically and economically significant
      predictors for the types of new patients that practices accept. These findings
      have important implications for both policy makers and private health care
      systems.

PMID- 27878711
TI  - A framework for guiding efforts to reward value instead of volume.
AB  - The U.S. healthcare system is in the midst of a major shift from fee-for-service
      to value-based reimbursement models. To date, these new reimbursement models have
      been focused on quality-contingent bonuses and cost-of-care risk sharing for
      providers, both of which have yielded only modest success.An analysis of health
      policy and business strategy literature was performed to identify the mechanisms
      of how value is rewarded in other industries and to understand the barriers to
      those mechanisms operating in the healthcare industry. A framework was developed
      to organize these findings. Rewarding healthcare providers for delivering value
      can only be achieved by enabling profitability to increase as value increases
      relative to competitors. Four variables determine a provider's profitability,
      each of which is considered as a potential lever to reward value with profit. The
      lever that offers the greatest potential is quantity (i.e., market share).
      Ironically, this means rewarding value with volume. The major barriers to value
      improvements being rewarded with market share are identified, and the profound
      impact of minimizing or removing those barriers is illustrated using a variety of
      examples from our healthcare system. Trending reforms that rely on quality
      contingent bonuses and cost-of-care risk sharing are limited in the degree of
      value improvement they will stimulate because they rely on ineffective levers to
      reward value; instead, reform efforts must focus on removing barriers to
      rewarding value with market share. The framework presented can be used to predict
      the impact of any proposed reform.

PMID- 27878712
TI  - Much ado about nothing? The financial impact of physician-owned specialty
      hospitals.
AB  - The U.S. hospital industry has recently witnessed a number of policy changes
      aimed at aligning hospital payments to costs and these can be traced to
      significant concerns regarding selection of profitable patients and procedures by
      physician-owned specialty hospitals. The policy responses to specialty hospitals
      have alternated between payment system reforms and outright moratoriums on
      hospital operations including one in the recently enacted Affordable Care Act. A
      key issue is whether physician-owned specialty hospitals pose financial strain on
      the larger group of general hospitals through cream-skimming of profitable
      patients, yet there is no study that conducts a systematic analysis relating such
      selection behavior by physician-owners to financial impacts within hospital
      markets. The current paper takes into account heterogeneity in specialty hospital
      behavior and finds some evidence of their adverse impact on profit margins of
      competitor hospitals, especially for-profit hospitals. There is also some
      evidence of hospital consolidation in response to competitive pressures by
      specialty hospitals. Overall, these findings underline the importance of the
      payment reforms aimed at correcting distortions in the reimbursement system that
      generate incentives for risk-selection among providers groups. The identification
      techniques will also inform empirical analysis on future data testing the
      efficacy of these payment reforms.

PMID- 27878713
TI  - Exit from catastrophic health payments: a method and an application to Malawi.
AB  - This paper proposes three measures of average exit time from catastrophic health
      payments; the first measure is non-normative in that the weights placed on
      catastrophic payments incurred by poor and nonpoor households are the same. It
      ignores the fact that the opportunity cost of health spending is different
      between poor and nonpoor households. The other two measures allow for
      distribution sensitivity but differ in their conceptualization of inequality; one
      is based on socioeconomic inequalities in catastrophic health payments, and the
      other uses pure inequalities in catastrophic health payments. The proposed
      measures are then applied to Malawian data from the Third Integrated Household
      Survey. The empirical results show that when the threshold of pre-payment income
      is increased from 5 to 15 %, the average exit time decreases from 2.1 to 0.2
      years; and as the catastrophic threshold rises from 10 to 40 % of ability to pay,
      the average exit time falls from 3.6 to 0.1 years. It is found that adjusting for
      socioeconomic inequality leads to small changes in the exit times, however, using
      pure inequality leads to large reductions in the exit time.

PMID- 27878715
TI  - Prescription drug coverage and chronic pain.
AB  - Chronic pain is one of the most common chronic conditions affecting more than 50
      % of older adults. While pain management can be quite complex, prescription drugs
      are the most commonly used treatment modality. In this study, I examine whether
      increased access to prescription drugs due to the introduction of the Medicare
      Part D program in 2006 led to better management of pain among the elderly. While
      prior work has identified increases in the utilization of analgesics due to the
      introduction of Medicare Part D, the extent to which this increase in drug use
      actually improved the well-being of older adults is not known. Using data from
      the Health and Retirement Study, I employ a difference-in-differences strategy
      that compares pre versus post 2006 changes in pain related outcomes between
      Medicare eligible persons and a younger ineligible group. I find that Medicare
      Part D significantly reduced pain related activity limitations among a sample of
      older adults who report being troubled by pain.

PMID- 27878714
TI  - Going beyond life expectancy in assessments of health systems' performance: life
      expectancy adjusted by perceived health status.
AB  - International comparisons of health systems data have been used to guide health
      policy. Health systems performance is generally evaluated on how different
      factors contribute to mortality and longevity. Fewer studies scrutinize the
      factors that determine morbidity in different countries, partly because
      indicators that assess morbidity on a country level are not as widely available
      as mortality and longevity data. We introduce a new health status indicator able
      to combine mortality and morbidity in a single composite measure for each country
      and gender at a point in time (LEAPHS), yielding the average number of years that
      men (women) can expect to live in "good" (or better) health. Using the Sullivan
      method we combine the mortality risk, calculated for specific age and gender
      groups, with perceived health status for the same age and gender groups, and we
      estimate how medical care and various socio-economic, environmental and
      structural, lifestyle, and technological factors affect LEAPHS and life
      expectancy at birth for a large panel of thirty OECD countries. We find that some
      variables (alcohol consumption, urbanization) have a significant effect on both
      LEAPHS and life expectancy, while one variable (the number of hospitals) has a
      significant effect for both genders on life expectancy only. However, the effects
      of many other variables (health expenditure per capita, health expenditure per
      capita squared, GDP growth, and technology) were only significant predictors for
      LEAPHS. This leads us to conclude that LEAPHS is able to capture the impact of
      some health determinants not captured by life expectancy at birth. While we
      believe this new measure may be useful for health economists and statisticians
      doing cross-country analyses, further comparisons with other measures may be
      useful.

PMID- 27878716
TI  - Inhibition of Tobacco Ringspot Virus by the Culture Fluid of L-Lysine-alpha
      Oxidase Producing Strain.
AB  - A producing strain of an anti-tumor and antiviral enzyme L-lysine-alpha-oxidase
      from Trichoderma was cultured using a technological device of G. K. Skryabin
      Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of
      Sciences (Pushchino). L-lysine-alpha-oxidase activity in the obtained metabolite
      concentrate was 5.4 U/ml. We studied the effects of the concentrate of active L
      lysine-alpha-oxidase producer on the highly infectious Tobacco ringspot virus and
      revealed anti-viral activity of it when enzyme concentration was at least 1.0
      U/ml.

PMID- 27878717
TI  - Antitumor Effects of Sorbus aucuparia L. Extract Highly Saturated with Anthocyans
      and Their Mechanisms.
AB  - The effects of Fructus Sorbi aucupariae extract, originally saturated with
      anthocyans, on the development of Lewis lung carcinoma and B-16 melanoma in
      C57Bl/6 mice and the efficiency of cyclophosphamide treatment were studied.
      Antitumor activity of the extract and potentiation of the antimetastatic activity
      of the cytostatic were demonstrated. Studies on melanoma B-16 model revealed an
      increase in the counts of stromal progenitor cells in the tumor node and their
      accelerated maturation after treatment with the extract. No effects towards the
      tumor stem and committed cells were detected.

PMID- 27878718
TI  - Proinflammatory Cytokines as Regulators of Vaginal Microbiota.
AB  - It was shown that IL-1beta, IL-8, and IL-6 in concentrations similar to those in
      the vagina of healthy women stimulated the growth of normal microflora
      (Lactobacillus spp.) and suppressed the growth and biofilm production by S.
      aureus and E. coli. On the contrary, these cytokines in higher concentrations
      typical of vaginal dysbiosis suppressed normal microflora and stimulated the
      growth of opportunistic microorganisms. TGF-beta1 in both doses produced a
      stimulating effects on study vaginal microsymbionts. It is hypothesized that pro
      inflammatory cytokines serve as the molecules of interspecies communication
      coordinating the interactions of all components of the vaginal symbiotic system.

PMID- 27878719
TI  - Transmural Differences in Mechanical Properties of Isolated Subendocardial and
      Subepicardial Cardiomyocytes.
AB  - We studied the differences in twitch force of subendocardial and subepicardial
      cardiomyocytes isolated from mouse left ventricular wall at different preloads
      using an original single cell stretch method recently developed by us. Then, we
      used our mathematical models of subendocardial and subepicardial cells to predict
      underlying cellular mechanisms. Transmural differences in the amplitudes of
      active tension of subendocardial and subepicardial cardiomyocytes were revealed
      that could be related to the differences in cooperative end-to-end interaction
      between the neighboring regulatory units of the thin filament.

PMID- 27878720
TI  - Selank Inhibits Ethanol-Induced Hyperlocomotion and Manifestation of Behavioral
      Sensitization in DBA/2 Mice.
AB  - The effect of non-benzodiazepine anxiolytics on the ethanol-induced
      hyperlocomotion and behavioral sensitization was assessed in male DBA/2 mice.
      Selank that enhances activity of the endogenous opioid system (0.3 mg/kg,
      intraperitoneally), similar to the nonselective opiate receptor blocker naloxone
      (1.0 mg/kg, intraperitoneally), prevented the development of ethanol-induced (2.0
      g/kg intraperitoneally) hyperlocomotion, in contrast to sigma1-receptors agonist
      Afobazole (1.0 mg/kg, intraperitoneally) that did not inhibit ethanol-induced
      behavioral stimulation. Single dose of Selank significantly blocked manifestation
      of motor sensitization without affecting its formation. These findings suggest
      that Selank can modulate the motivational effects of ethanol.

PMID- 27878721
TI  - Evaluation In Vitro of Immunoregulatory Cytokines Secretion by Dendritic Cells in
      Mountain Skiers.
AB  - In vitro production of immunoregulatory cytokines (IFN-alpha, IL-31, TNF-beta, IL
      17A, IL-7, IL-1RA, IL-1alpha, IL-10, IL-15, IL-21, IL-22, IL-23, IL-27, and IL-9)
      by dendritic cell cultures was compared in ski athletes and healthy donors.
      Effect of prolonged intense physical exercise on secretory activity of immune
      cells was investigated. In both groups, secretion of IL-1RA, IL-10, IL-1alpha by
      dendritic cells was revealed, but there were significant differences in IL-1RA,
      IL-1alpha content (p<0.05) with lower level in the group of athletes. Production
      of IL-17A and IL-7 by dendritic cells in the group of athletes was not detected.
      In athletes, several proinflammatory cytokines (IFN-alpha, IL-31, and TNF-beta)
      were secreted by cells in high concentrations, in contrast to the control group.
      In both groups, dendritic cells did not secrete IL-15, IL-21, IL-22, IL-23, IL
      27, and IL-9.

PMID- 27878722
TI  - Role of PI3K, MAPK/ERK 1/2, and p38 in Production of Erythropoietic Activity by
      Bone Marrow Cells after Blood Loss.
AB  - The leading role in the regulation of erythropoietic activity of adherent bone
      marrow cells under conditions of post-hemorrhagic anemia is played by classical
      MAP kinase pathway (ERK pathway). Erythropoietin is not the decisive factor in
      the formation of erythropoietic activity of adherent cells. PI3K, MAPK/ERK 1/2,
      and p38-signaling proteins are not the main regulators of local production of
      erythropoietin after 30% loss of circulating blood volume.

PMID- 27878723
TI  - Antioxidant and Antimutagenic Metabolites in Animals with Opposite Sensitivity to
      Tuberculosis Mycobacteria and Mutagenic Xenobiotics.
AB  - Different sensitivity of guinea pigs and rats to Mycobacterium tuberculosis and
      membranotropic mutagenic xenobiotics is associated with differences in the
      metabolism of amino acid precursors of phospholipids. In turn, specific features
      of phospholipid metabolism are determined by differences in the level of sulfur
      containing regulatory metabolites (methionine, taurine, and glutathione) in
      tissues. Taurine and methionine increase organism's resistance to Mycobacterium
      tuberculosis (typical of rats), glutathione and its constituent amino acids
      improve resistance to the mutagenic effects of xenobiotics (typical of guinea
      pigs). These metabolites can be used for strengthening of natural resistance to
      tuberculosis and mutagenic and carcinogenic xenobiotics.

PMID- 27878724
TI  - Production of Recombinant Polypeptides Containing One GA-Module and Analysis of
      Their Ability to Bind to Human Albumin.
AB  - Surface proteins of many bacterial species interact with human serum albumin
      (HSA) via a special region of amino acid sequence termed GA module. For instance,
      surface peptostreptococcal albumin-binding protein of anaerobic bacteria
      Peptostreptococcus magnus contains one HSA-binding GA-module. Protein G from
      group G and C Streptococcus strains isolated from humans has HSA-binding region
      consisting of three GA-modules. HSA-binding protein containing two GA-modules was
      found in strains of group G Streptococcus of animal origin. We obtained two
      recombinant polypeptides GA1 and GA2 congaing one GA-module each. Recombinant
      polypeptide with two GA-modules binds HSA with a much higher affinity than
      polypeptides GA1 and GA2 containing one GA-module. Polypeptide with the second
      GAmodule more effectively binds HSA than polypeptides with the GA-module.

PMID- 27878725
TI  - Effect of Cardiac Myosin-Binding Protein C on Tropomyosin Regulation of Actin
      Myosin Interaction Using In Vitro Motility Assay.
AB  - We studied the modulating role of cardiac myosin-binding protein C (cMyBP-C) in
      tropomyosin regulation of the actin-myosin interaction. The effect of cMyBP-C on
      the velocity of actin-tropomyosin filament sliding over cardiac and slow skeletal
      myosins was evaluated using in vitro motility assay. The effect of cMyBP-C on the
      actin-tropomyosin filaments sliding depended on the type of myosin. The
      regulatory effect of cMyBP-C differs for cardiac and slow skeletal myosin because
      of the presence of specific essential light chain (LC1sa) in slow skeletal myosin
      isoform.

PMID- 27878726
TI  - Association of -717A>G Polymorphism in the C-Reactive Protein Gene (CRP) with
      Schizotypal Personality Traits.
AB  - Associations between schizotypal traits and genes coding for inflammation markers
      (Creactive protein and TNF-alpha) were studied in 222 healthy men who completed
      the Schizotypal Personality Questionnaire (SPQ-74). CRP -717A>G and TNFalpha -308
      G>A polymorphisms were genotyped. Carriers of low-active allele G of the CRP gene
      differed from subjects with genotype AA by a trend toward more manifest
      schizotypal traits in general and scores on the Interpersonal factor, which
      corresponds to negative syndrome in schizophrenia, and Constricted affect and Odd
      behavior scales. These results could be interpreted in favor of the hypothesis on
      a compensatory increase of CRP concentrations in subjects with abnormalities of
      CNS development that predispose to schizophrenia.

PMID- 27878727
TI  - Effectiveness of Lifestyle Modification in Corrections of States Associated with
      Metabolic Syndrome.
AB  - In a 3-month study, 30 obese patients were assigned to lifestyle modification
      therapy, which is the major component of all modern strategies correcting the
      metabolic syndrome. The 3-month course of non-pharmacological therapy
      significantly diminished the major index evaluating the state of these patients,
      i.e., the risk of cardiovascular disasters. This therapy positively affected all
      the states associated with metabolic syndrome: arterial BP attained the targets
      in 53% patients together with normalization of their nocturnal arterial BP
      dipping status; the lipid panel and carbohydrate metabolic indices normalized in
      46 and 44% patients, respectively; hepatic steatosis moderated in 56% patients;
      and the disturbances in hemostasis were annihilated in 67% patients.

PMID- 27878728
TI  - Structural Organization of Cerebral Basolateral Nucleus of the Amygdaloid Complex
      in WAG-Rij Rats with Different Genotypes by the TAQ 1A Locus of Dopamine 2
      Receptor Gene (DRD2).
AB  - Anxiety levels and structural organization of the basolateral nucleus of the
      amygdaloid complex were analyzed in WAG/Rij rats with genotypes A1/A1 and A2/A2
      by DRD2 locus Taq 1A. Association of anxious behavior with A2/A2 genotype and the
      relationship between the structural organization of the nucleus and polymorphic
      variants of this locus are detected.

PMID- 27878729
TI  - Features of the Left Ventricular Functional Geometry in Patients with Myocardial
      Diseases with Varying Degrees of Systolic Dysfunction.
AB  - We revealed some features of the left ventricular functional geometry in patients
      with myocardial diseases with different degrees of left ventricular systolic
      dysfunction. A negative correlation was found between the spatio-temporal
      heterogeneity of the kinetics of the left ventricular wall during systole and
      ejection fraction in normal heart and in systolic dysfunction. The differences in
      the quantitative characteristics of the functional geometry between patients and
      normal subjects and between different groups of patients depended on the
      severityof left-ventricular systolic dysfunction. In particular, spatial
      heterogeneity index that characterizes heterogeneity of systolic movement of the
      wall segments and end-systolic Fourier shape-power index characterizing
      complexity of the left ventricle shape during systole differed significantly in
      the examined groups of patients and have the greatest diagnostic power.

PMID- 27878730
TI  - Mesenchymal-Epithelial Transition in Culture of Stromal Progenitor Cells Isolated
      from the Liver of a Patient with Alcoholic Cirrhosis.
AB  - The cells isolated from biopsy specimen of a patient with alcoholic liver
      cirrhosis and cultured under standard conditions for obtaining stromal cell
      culture clearly diverged during early passages into two morphologically and
      phenotypically different subtypes: epithelial and mesenchymal. Mesenchymal cells
      expressed CD90 and CD44 and epithelial cells expressed CD166, CD227, and
      hepatocyte growth factor receptor Met. Starting from passage 6, the culture
      underwent spontaneous morphological changes and by passages 8-10 contained only
      epithelium-like cells. CD90 and CD44 expression disappeared, CD166 and CD227
      expression remained unchanged, and Met expression increased. A small fraction of
      cells expressed GATA-4, HNF3beta, HNF1alpha, and HNF4alpha. After addition of
      inducers of hepatogeneic differentiation, the cells started producing albumin.

PMID- 27878732
TI  - Endomorphins and beta-Endorphin Do Not Affect Heart Tolerance to the Pathogenic
      Effect of Reperfusion.
AB  - Selective agonists of MU1- and MU2-opioid receptors endomorphin-2 and endomorphin
      1 injected intravenously in a dose of 4500 nmol/kg in 5 min before coronary blood
      flow resumption had no effect on cardiac reperfusion damage. Consequently, MU1-
      and MU2-opioid receptors are not involved in the regulation of heart tolerance to
      reperfusion injury. Nonselective opioid receptor agonist beta-endorphin (100
      nmol/kg) also did not affect heart tolerance to the pathogenic effect of
      reperfusion.

PMID- 27878731
TI  - Effect of Cardiomyopathic Mutations in Tropomyosin on Calcium Regulation of the
      Actin-Myosin Interaction in Skeletal Muscle.
AB  - Tropomyosin plays an important role in the regulation of actin-myosin interaction
      in striated muscles. Mutations in the tropomyosin gene disrupt actin-myosin
      interaction and lead to myopathies and cardiomyopathies. Tropomyosin with
      mutations in the alpha-chain is expressed in both the myocardium and skeletal
      muscles. We studied the effect of mutations in the alpha-chain of tropomyosin
      related to hypertrophic (D175N and E180G) and dilated cardiomyopathies (E40K and
      E54K) on calcium regulation of the actin-myosin interaction in skeletal muscles.
      We analyzed the calcium-dependent sliding velocity of reconstructed thin
      filaments containing F-actin, troponin, and tropomyosin over myosin surface in an
      in vitro motility assay. Mutations D175N and E180G in tropomyosin increased the
      sliding velocity and its calcium sensitivity, while mutation E40K reduced both
      these parameters. E54K mutation increased the sliding velocity of thin filaments,
      but did not affect its calcium sensitivity.

PMID- 27878734
TI  - CB-Receptor Agonist HU-210 Mimics the Postconditioning Phenomenon of Isolated
      Heart.
AB  - CB receptor agonist HU-210 exhibits an infarction-limiting effect during in vitro
      reperfusion of the heart after focal ischemia. This effect is paralleled by a
      decrease in left-ventricular developed pressure and double product. In addition,
      HU-210 reduces end-diastolic pressure during the reperfusion period, which
      indirectly attests to reduced Ca2+ overload of cardiomyocytes.

PMID- 27878733
TI  - Hypolipidemic Effect of Mannan in Mice with Acute Lipemia Induced by Poloxamer
      407.
AB  - We studied biological effects of mannan, a polysaccharide immunomodulator from C.
      albicans, that interacts with mannose receptor in vivo. It is shown that
      preliminary administration of mannan (5 times in a dose of 50 mg/kg or 2 times in
      a dose of 100 mg/kg) to mice with acute lipemia induced by lipase inhibitor
      poloxamer 407 (300 mg/kg) reduces the serum concentrations of atherogenic LDL,
      cholesterol, and triglycerides. Administration of mannan to intact mice and
      animals with acute lipemia reduces triglyceride concentration and causes
      labilization of lysosomal membranes in the liver. Serum activity of
      chitotriosidase, a marker of macrophage activation, was elevated in mice with
      acute lipemia treated with mannan. Thus, mannan from C. albicans is a promising
      hypolipidemic polysaccharide compound, similar by its activity to beta-glycan, a
      component of LPS.

PMID- 27878735
TI  - A multi-material coating containing chemically-modified apatites for combined
      enhanced bioactivity and reduced infection via a drop-on-demand micro-dispensing
      technique.
AB  - Prevention of infection and enhanced osseointegration are closely related, and
      required for a successful orthopaedic implant, which necessitate implant designs
      to consider both criteria in tandem. A multi-material coating containing 1:1
      ratio of silicon-substituted hydroxyapatite and silver-substituted hydroxyapatite
      as the top functional layer, and hydroxyapatite as the base layer, was produced
      via the drop-on-demand micro-dispensing technique, as a strategic approach in the
      fight against infection along with the promotion of bone tissue regeneration. The
      homogeneous distribution of silicon-substituted hydroxyapatite and silver
      substituted hydroxyapatite micro-droplets at alternate position in silicon
      substituted hydroxyapatite-silver-substituted hydroxyapatite/hydroxyapatite
      coating delayed the exponential growth of Staphylococcus aureus for up to 24 h,
      and gave rise to up-regulated expression of alkaline phosphatase activity, type I
      collagen and osteocalcin as compared to hydroxyapatite and silver-substituted
      hydroxyapatite coatings. Despite containing reduced amounts of silicon
      substituted hydroxyapatite and silver-substituted hydroxyapatite micro-droplets
      over the coated area than silicon-substituted hydroxyapatite and silver
      substituted hydroxyapatite coatings, silicon-substituted hydroxyapatite-silver
      substituted hydroxyapatite/hydroxyapatite coating exhibited effective
      antibacterial property with enhanced bioactivity. By exhibiting good
      controllability of distributing silicon-substituted hydroxyapatite, silver
      substituted hydroxyapatite and hydroxyapatite micro-droplets, it was demonstrated
      that drop-on-demand micro-dispensing technique was capable in harnessing the
      advantages of silver-substituted hydroxyapatite, silicon-substituted
      hydroxyapatite and hydroxyapatite to produce a multi-material coating along with
      enhanced bioactivity and reduced infection.

PMID- 27878736
TI  - In vitro cyto-biocompatibility study of thin-film transistors substrates using an
      organotypic culture method.
AB  - Thin-Film-Transistors Liquid-Crystal Display has become a standard in the field
      of displays. However, the structure of these devices presents interest not only
      in that field, but also for biomedical applications. One of the key components,
      called here TFT substrate, is a glass substrate with a dense and large array of
      thousands of transparent micro-electrodes that can be considered as a large scale
      multi-electrode array(s). Multi-electrode array(s) are widely used for in vitro
      electrical investigations on neurons and brain, allowing excitation,
      registration, and recording of their activity. However, the range of application
      of conventional multi-electrode array(s) is usually limited to some tens of cells
      in a homogeneous cell culture, because of a small area, small number and a low
      density of the micro-electrodes. TFT substrates do not have these limitations and
      the authors are currently studying the possibility to use TFT substrates as new
      tools for in vitro electrical investigation on tissues and organoids. In this
      respect, experiments to determine the cyto-biocompatibility of TFT substrates
      with tissues were conducted and are presented in this study. The investigation
      was performed using an organotypic culture method with explants of brain and
      liver tissues of chick embryos. The results in term of morphology, cell
      migration, cell density and adhesion were compared with the results from
      Thermanox(r), a conventional plastic for cell culture, and with
      polydimethylsiloxane, a hydrophobic silicone. The results with TFT substrates
      showed similar results as for the Thermanox(r), despite the TFT hydrophobicity.
      TFT substrates have a weak cell adhesion and promote cell migration similarly to
      Thermanox(r). It could be concluded that the TFT substrates are cyto
      biocompatible with the two studied organs.

PMID- 27878737
TI  - Sebelipase Alfa: A Review in Lysosomal Acid Lipase Deficiency.
AB  - Sebelipase alfa (Kanuma(r), KanumaTM), the first commercially available
      recombinant human lysosomal acid lipase (LAL), is approved in various countries
      worldwide, including those of the EU, the USA and Japan, as a long-term enzyme
      replacement therapy for patients diagnosed with LAL deficiency (LAL-D), an ultra
      rare, autosomal recessive, progressive metabolic liver disease. In an ongoing
      study in nine infants presenting with early-onset LAL-D (Wolman disease), open
      label treatment with sebelipase alfa significantly improved 1-year survival
      compared with historical controls. A substantial mortality benefit was maintained
      at 2 years of age, as was a reduction in disease-related activity. In an ongoing
      study of 66 children and adults with late-onset LAL-D (cholesteryl ester storage
      disease), 20 weeks' double-blind treatment with sebelipase alfa significantly
      reduced multiple disease-related hepatic and lipid abnormalities compared with
      placebo. Sustained improvements in markers of liver damage and dyslipidaemia were
      seen after 76 weeks' open-label treatment in an extension of this trial and,
      similarly, after 2 years' open-label treatment in an extension of another study
      in nine adults with late-onset LAL-D. Sebelipase alfa therapy has thus far been
      generally well tolerated, with signs and symptoms consistent with anaphylaxis
      being the most serious adverse reactions experienced by patients receiving the
      drug in clinical trials. Due to the rarity of the disease, these studies have
      enrolled a limited number of patients. Nonetheless, the available data indicate
      that sebelipase alfa is an effective disease-specific therapy for individuals
      with LAL-D who have historically been managed using supportive therapies (e.g.
      cholesterol reduction, hematopoietic stem cell transplantation, and liver
      transplantation).

PMID- 27878738
TI  - Size Constancy is Preserved but Afterimages are Prolonged in Typical Individuals
      with Higher Degrees of Self-Reported Autistic Traits.
AB  - Deficits in perceptual constancies from early infancy have been proposed to
      contribute to autism and exacerbate its symptoms (Hellendoorn et al., Frontiers
      in Psychology 6:1-16, 2015). Here, we examined size constancy in adults from the
      general population (N = 106) with different levels of self-reported autistic
      traits using an approach based on negative afterimages. The afterimage strength,
      as indexed by duration and vividness, was also quantified. In opposition to the
      Hellendoorn and colleagues' model, we were unable to demonstrate any kind of
      relationship between abilities in size constancy and autistic traits. However,
      our results demonstrated that individuals with higher degrees of autistic traits
      experienced more persistent afterimages. We discuss possible retinal and post
      retinal explanations for prolonged afterimages in people with higher levels of
      autistic traits.

PMID- 27878740
TI  - Brief Report: A Comparison of the Preference for Viewing Social and Non-social
      Movies in Typical and Autistic Adolescents.
AB  - The recently proposed Social Motivation theory (Chevallier et al., Trends in
      cognitive sciences 16(4):231-239, 2012) suggests that social difficulties in
      Autism Spectrum Condition (ASC) might be caused by a difference in the motivation
      to engage with other people. Here we compared adolescents with (N = 31) and
      without (N = 37) ASC on the Choose-a-Movie paradigm that measures the social
      seeking. The results showed a preference for viewing objects over smiling faces
      in ASC, which is in line with the theory of low social motivation. However,
      typical adolescents did not show any stimuli preferences, raising questions about
      developmental changes in social motivation. Age was found to play a significant
      role in moderating the choice behaviour of the participants. We discuss the
      implications of these findings in detail.

PMID- 27878739
TI  - Divergence of Age-Related Differences in Social-Communication: Improvements for
      Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder.
AB  - Although social-communication difficulties and repetitive behaviors are hallmark
      features of autism spectrum disorder (ASD) and persist across the lifespan, very
      few studies have compared age-related differences in these behaviors between
      youth with ASD and same-age typically developing (TD) peers. We examined this
      issue using SRS-2 (Social Responsiveness Scale-Second Edition) measures of social
      communicative functioning and repetitive behaviors in a stratified cross
      sectional sample of 324 youth with ASD in the absence of intellectual disability,
      and 438 TD youth (aged 4-29 years). An age-by-group interaction emerged
      indicating that TD youth exhibited age-related improvements in social
      communication scores while the ASD group demonstrated age-related declines in
      these scores. This suggests that adolescents/adults with ASD may fall
      increasingly behind their same-age peers in social-communicative skills.

PMID- 27878741
TI  - Coexistence of 9p Deletion Syndrome and Autism Spectrum Disorder.
AB  - Deletion or duplication of the short arm of chromosome 9 may lead to a variety of
      clinical conditions including craniofacial and limb abnormalities, skeletal
      malformations, mental retardation, and autism spectrum disorder. Here, we present
      a case report of 5-year-old boy with 9p deletion syndrome and autism spectrum
      disorder.

PMID- 27878742
TI  - Brief Report: Diminished Gaze Preference for Dynamic Social Interaction Scenes in
      Youth with Autism Spectrum Disorders.
AB  - In this study, we present an eye-tracking paradigm, adapted from previous work
      with toddlers, for assessing social-interaction looking preferences in youth ages
      5-17 with ASD and typically-developing controls (TDC). Videos of children playing
      together (Social Scenes, SS) were presented side-by-side with animated geometric
      shapes (GS). Participants with ASD demonstrated reduced SS preferences compared
      to TDC, results also represented continuously by associations between higher SS
      preferences and fewer social difficulties across the combined sample. Exploratory
      analyses identified associations between increased SS preferences and higher
      Vineland Daily Living Skills in ASD and suggested SS preferences in TDC females
      might drive ASD versus TDC between-group differences. These findings describe
      potentially sex-linked couplings between preferences for social information and
      social functioning in school-aged children.

PMID- 27878743
TI  - Production of Ethanol From Newly Developed and Improved Winter Barley Cultivars.
AB  - Winter barley has attracted strong interest as a potential feedstock for fuel
      ethanol production in regions with mild winter climate such as the mid-Atlantic
      and northeastern USA. Ten recently developed and improved winter barley cultivars
      and breeding lines including five hulled and five hull-less lines were
      experimentally evaluated for potential ethanol production. The five hulled barley
      lines included three released cultivars (Thoroughbred, Atlantic, and Secretariat)
      and two breeding lines (VA09B-34 and VA11B-4). The five hull-less lines also
      included three released cultivars (Eve, Dan, and Amaze 10) and two breeding lines
      (VA08H-65 and VA13H-34). On the average, the hull-less barley cultivars produced
      more ethanol per unit mass because of their higher starch and beta-glucan
      contents. However, since the hulled barley cultivars had higher agronomic yield,
      the potential ethanol production per acre of land for the two types were
      approximately equal. Among the ten cultivars tested, the hull-less cultivar Amaze
      10 was the best one for ethanol production. The ethanol yield values obtained for
      this cultivar were 2.61 gal per bushel and 292 gal per acre.

PMID- 27878744
TI  - Protective Effect of Saccharomyces boulardii on Deoxynivalenol-Induced Injury of
      Porcine Macrophage via Attenuating p38 MAPK Signal Pathway.
AB  - The aims of our study were to evaluate the effects of Saccharomyces boulardii (S.
      boulardii) on deoxynivalenol (DON)-induced injury in porcine alveolar macrophage
      cells (PAMCs) and to explore the underlying mechanisms. 3-(4,5-Dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, ELISA,
      qRT-PCR, and western blot were performed to assess whether S. boulardii could
      prevent DON-induced injury by p38 mitogen-activated protein kinase (p38 MAPK)
      signal pathway. The results showed that pretreatment with 8 MUM DON could
      decrease the viability of PAMC and significantly increase the apoptosis rate of
      PAMC, whereas S. boulardii could rescue apoptotic PAMC cells induced by DON.
      Further experiments revealed that S. boulardii effectively reversed DON-induced
      cytotoxicity via downregulating the expression of TNF-alpha, IL-6, and IL-lbeta.
      In addition, S. boulardii significantly alleviated DON-induced phosphorylation
      and mRNA expression of p38 and further increased the expression of apoptosis
      regulation genes Bcl-xl and Bcl-2 and inhibited the activation of Bax. Our
      results suggest that S. boulardii could suppress DON-induced p38 MAPK pathway
      activation and reduce the expression of downstream inflammatory cytokines, as
      well as promote the expression of anti-apoptotic genes to inhibit apoptosis
      induced by DON in PAMC.

PMID- 27878745
TI  - Characterization of a Marine Microbial Community Used for Enhanced Sulfate
      Reduction and Copper Precipitation in a Two-Step Process.
AB  - Marine microorganisms that are obtained from hydrothermal vent sediments present
      a great metabolic potential for applications in environmental biotechnology.
      However, the work done regarding their applications in engineered systems is
      still scarce. Hence, in this work, the sulfate reduction process carried out by a
      marine microbial community in an upflow anaerobic sludge blanket (UASB) reactor
      was investigated for 190 days under sequential batch mode. The effects of 1000 to
      5500 mg L-1 of SO4-2 and the chemical oxygen demand (COD)/SO4-2 ratio were
      studied along with a kinetic characterization with lactate as the electron donor.
      Also, the feasibility of using the sulfide produced in the UASB for copper
      precipitation in a second column was studied under continuous mode. The system
      presented here is an alternative to sulfidogenesis, particularly when it is
      necessary to avoid toxicity to sulfide and competition with methanogens. The
      bioreactor performed better with relatively low concentrations of sulfate (up to
      1100 mg L-1) and COD/SO4-2 ratios between 1.4 and 3.6. Under the continuous
      regime, the biogenic sulfide was sufficient to precipitate copper at a removal
      rate of 234 mg L-1 day-1. Finally, the identification of the microorganisms in
      the sludge was carried out; some genera of microorganisms identified were
      Desulfitobacterium and Clostridium.

PMID- 27878746
TI  - Electricity Production and Characterization of High-Strength Industrial
      Wastewaters in Microbial Fuel Cell.
AB  - Microbial fuel cells (MFCs) convert electrochemical energy into electrical energy
      immediately and have a big potential usage for the same time wastewater treatment
      and energy recovery via electro-active microorganisms. However, MFCs must be
      efficiently optimized due to its limitations such as high cost and low power
      production. Finding new materials to increase the cell performance and reduce
      cost for MFC anodes is mandatory. In the first step of this study, different
      inoculation sludges such as anaerobic gum industry wastewater, anaerobic brewery
      wastewater and anaerobic phosphate were tested, and MFC that was set up with
      anaerobic gum industry wastewater inoculation sludge exhibited the highest
      performance. In the second step of this study, various wastewaters such as
      chocolate industry, gum industry and slaughterhouse industry were investigated
      for anode bacteria sources. Several electrochemical techniques have been employed
      to elucidate how wastewaters affect the MFCs' performance. Among all the
      mentioned wastewaters, the best performance was achieved by the MFCs fed with
      slaughterhouse wastewater; this device produced a maximum power density of 267
      mW.m-2.

PMID- 27878748
TI  - Erratum to: Delivery of the Porcupine Inhibitor WNT974 in Mice.

PMID- 27878749
TI  - The combination of osthole with baicalin protects mice from Staphylococcus aureus
      pneumonia.
AB  - We reported the inhibition of alpha-Hemolysin (Hla) production in methicillin
      resistant Staphylococcus aureus USA300 by osthole and further investigated the
      combination of osthole and baicalin in the treatment of staphylococcal pneumonia.
      Using cytotoxicity assays and a mouse model of intranasal lung infection, we
      evaluated the effect of combined therapy. Our results suggest that the
      combination of osthole and baicalin alleviated S. aureus-mediated A549 cell
      injury and protected mice from S. aureus pneumonia.

PMID- 27878750
TI  - The relationship between patients' knowledge of diabetes therapeutic goals and
      self-management behaviour, including adherence.
AB  - : Background The Middle East region has one the highest prevalence rates of
      diabetes in the world. Little is known about the determinants of adherence and
      the role of knowledge in diabetes self-management within these populations.
      Objective To investigate the relationship between patients knowledge of diabetes
      therapeutic targets with adherence to self-care measures in a sample of patients
      with type 2 diabetes in Kuwait. Setting Primary care chronic care clinics within
      the Ministry of Health of Kuwait. Methods A cross sectional survey was carried
      out with 238 patients from six clinics. A multistage stratified clustered
      sampling method was used to first randomly select the clinics and the patients.
      MAIN OUTCOME MEASURE: Self-reported adherence to three behaviours: medication
      taking, diet and physical activity. Results Respondents were able to correctly
      report a mean (SD) of 1.6 (1.3) out of 5 of the pre-specified treatment targets.
      Optimal adherence to physical activity, diet and medications was reported in 25,
      33 and 47 % of the study cohort, respectively. A structural equation model
      analysis showed better knowledge of therapeutic goals and own current levels
      translated into better adherence to medications, diet and physical activity.
      Conclusion Knowledge of therapeutic goals and own recent levels is associated
      with adherence to medications, diet, or physical activity in this Kuwaiti cohort
      of patients with diabetes. Low adherence to self-care management and poor overall
      knowledge of diabetes is a big challenge to successful diabetes care in Kuwait.

PMID- 27878752
TI  - Re: Abdel-Kader MS. Evaluation of the efficacy of sexual intercourse in expulsion
      of distal ureteric stones. Int Urol Nephrol 2016 [Epub ahead of print].

PMID- 27878751
TI  - Assessment of the relationship between serum paraoxonase activity and epicardial
      adipose tissue in hemodialysis patients.
AB  - PURPOSE: Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated (HDL)
      enzyme, which has been shown to reduce susceptibility to low-density lipoprotein
      (LDL) peroxidation. Epicardial adipose tissue (EAT) is a marker of
      atherosclerosis. The aim of this study was to determine the relationship between
      PON-1 activity and EAT in hemodialysis (HD) patients. METHODS: This is a cross
      sectional study conducted on 72 (43 males) HD patients with end-stage renal
      disease. Serum levels for lipid profiles, C-reactive protein, calcium, phosphate,
      and parathyroid hormone were measured. PON-1 activity was also measured and
      compared to the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol.
      Echocardiography was used to measure EAT thickness (EATT). The correlation
      between PON-1 and EATT was assessed, while independent predictors of EATT in HD
      patients were similarly assessed using multivariate regression analysis. RESULTS:
      There was a significant low mean value of PON-1 activity in HD patients compared
      with the control group (82.1 +/- 31.6 vs. 164.3 +/- 61.5 U/l, p = 0.0001) and
      significant high mean value of EATT in HD patients, compared with controls (6.2
      +/- 1.7 vs. 3.9 +/- 1.1 mm, p = 0.0001). In addition, there was a significant
      negative correlation between PON-1 activity and EATT (r = -0.484, p = 0.0001) and
      a significant positive correlation between PON-1 activity and HDL-C (r = 0.417, p
      = 0.0003). PON-1, total cholesterol, triglycerides, LDL, HDL, age, and body mass
      index were found to be independent predictors of EATT. CONCLUSION: Our study
      demonstrated that PON-1 activity was significantly lower in HD patients compared
      with healthy controls and that PON-1 activity was inversely correlated with EATT
      in this population.

PMID- 27878753
TI  - Helicobacter pylori Does not Affect Postoperative Outcomes After Sleeve
      Gastrectomy.
AB  - BACKGROUND: The effect of Helicobacter pylori (HP) colonization of the stomach of
      patients undergoing laparoscopic sleeve gastrectomy (LSG) is unclear. OBJECTIVE:
      The objective of this study is to evaluate the effect of HP colonization on
      postoperative outcomes of LSG. SETTING: The setting of this study is in
      University Hospital. METHODS: This study was a retrospective cohort study of
      prospectively maintained database of all patients who underwent LSG at Jordan
      University Hospital from 2008 to 2015. RESULTS: Five hundred patients were
      included (362 females and 138 males). The mean preoperative weight was 124.5 +/-
      23.8 kg. The mean preoperative body mass index (BMI) was 45.5 +/- 6.9 kg/m2. Two
      hundred sixteen (43.2%) patients were found to be HP positive. The differences
      between the HP positive and negative groups in respect of sex, baseline weight,
      and BMI were not statistically significant. However, patients who were HP
      positive were significantly older. All patients were followed for at least 3
      months. We had an overall complication rate of 2.6%. Differences in the
      complication rate between the two groups were not statistically significant.
      Follow-up was 61% at 1 year. The mean percent total weight loss (%TWL) was 32.9
      +/- 7.9, and the mean percent excess weight loss (%EWL) was 76.9 +/- 21.1. The
      decrease in BMI was 15.2 +/- 5.2. The difference between the two groups was not
      statistically significant. CONCLUSION: There is no clear association between HP
      infection at the time of surgery and postoperative complications, especially
      leaks.

PMID- 27878754
TI  - Efficiency and Safety Effects of Applying ERAS Protocols to Bariatric Surgery: a
      Systematic Review with Meta-Analysis and Trial Sequential Analysis of Evidence.
AB  - Application of the enhanced recovery after surgery (ERAS) to the bariatric
      surgical procedures is at its early stages with little consolidated evidence.
      This meta-analysis evaluates present literature and indicates pathways for
      development of evidence-based standardized ERAS protocols for bariatric surgery.
      Comparative trials between ERAS and conventional bariatric surgery published till
      June 2016 were searched in the medical database. Comparisons were made for length
      of stay (LOS), readmission, complications (major/minor), and reoperation rates.
      Trial sequential analysis (TSA) for the strength of meta-analysis was performed
      for the primary outcome LOS. Five subgroups with a total of 394 and 471 patients
      in ERAS and conventional group respectively were included. LOS was shorter in
      ERAS group by 1.56 +/- 0.18 days (random-effects, p < 0.001, I 2 = 93.07 %). The
      sample size in ERAS was well past the "information size" variable which was
      calculated to be 189 as per the TSA for power 85%. MH odds ratio [1.41 (95% CI
      1.13 to1.76)] was higher for minor complications in the ERAS group (fixed
      effects, I 2 = 0, p < 0.001). Superiority/inferiority of ERAS could not be
      established for major or overall complications, readmission, and anastomotic leak
      rates. No publication bias was found in the included trials (Egger's test, X
      intercept = 6.14, p = 0.66). Evaluation based on Cochrane collaboration
      recommendations suggested that all the five included trials had a high risk of
      methodological bias. ERAS protocols for bariatric procedures allow faster return
      to home for patients. The present bariatric ERAS protocols have high
      heterogeneity and would benefit from standardization. Minor complication rates
      increase with implementation of ERAS, however without any significant effect on
      overall patient morbidity. Further randomized trials comparing ERAS with
      conventional care are required to consolidate these findings.

PMID- 27878755
TI  - Double Pigtail Stent Insertion for Healing of Leaks Following Roux-en-Y Gastric
      Bypass. Our Experience (with Videos).
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is complicated by a leak in 0-4.3% of
      cases. Treatment by fully covered stents has been reported to be associated with
      some life-threatening complications. We report our experience of insertion of
      double pigtail stents. METHODS: Thirty-three patients (20M, 43 years-20/65),
      presenting with a leak at an average of 10 days after RYGB (4-35), were treated
      by double pigtail stent insertion and a nasojejunal feeding tube. Sixty percent
      of these patients had undergone surgical drainage prior to stenting for control
      of sepsis. Thirty leaks were located at the top of staple line and three at the
      gastro-jejunal anastomosis. At a 4-weekly follow-up, ablation or re-stenting was
      performed depending on status of fistula closure and patients were placed on
      normal diet. RESULTS: At the first follow-up, 10/33 fistulae healed, one patient
      presented with clinical failure (3%) and needed surgery, and 22/33were re
      stented. Twenty-one out of these 22 developed a secondary sub-clinical gastro
      gastric fistula and one, instead, developed complex (gastro-gastric, gastro
      colic) fistula. All (22) primary fistulae healed following four more weeks of
      treatment. Average treatment duration was of 61 days (28-99). Thirty-two patients
      (97%) at a follow-up of 1-33 months are asymptomatic. CONCLUSIONS: Leaks
      following RYGB can be successfully and safely managed by double pigtail stents.
      Upper gastric staple line leaks are responsible for the formation of a secondary
      sub-clinic gastro-gastric fistula which needs no additional treatment.

PMID- 27878756
TI  - Imaging findings of adrenal primitive neuroectodermal tumors: a series of seven
      cases.
AB  - OBJECTIVE: To explore the imaging features of adrenal primitive neuroectodermal
      tumors (PNETs). MATERIALS AND METHODS: This retrospective study included seven
      patients with surgically and pathologically confirmed adrenal PNETs. Among them,
      six underwent computed tomography (CT) scans, and one underwent magnetic
      resonance imaging. The imaging findings, including size, shape, margin,
      hemorrhage, calcification, cystic degeneration, regional lymph nodes involvement,
      tumor thrombus formation and enhancement pattern, were retrospectively analyzed.
      RESULTS: Among the seven adrenal PNET patients, six were male, and one was
      female. The median age was 26 years (range 2-56 years). The disease generally
      presented with either insidious symptoms (n = 4) or non-specific symptoms,
      including right flank pain (n = 1) and left upper abdominal discomfort (n = 2).
      On the pre-enhanced CT images, the tumor usually appeared as a well-defined,
      rounded or oval, heterogeneous mass without calcification. Certain tissue
      characteristics, such as cystic degeneration (n = 5), capsule (n = 4) and
      hemorrhage (n = 2), were observed. Regional lymph node involvement was observed
      in three cases, and renal vein thrombus was observed in one case. All cases
      showed mild heterogeneous enhancement of the tumor on the enhanced CT images.
      CONCLUSION: An adrenal PNET commonly presents as a relatively large, well
      defined, heterogeneous mass with cystic degeneration, necrosis and a
      characteristic mild contrast-enhancement pattern on multiphase enhanced images.
      PNET should be considered when the diagnosis of common tumors is not favored by
      signs on images. CLINICAL TRIAL REGISTRATION STATEMENT: This study was approved
      by the medical ethics committee of Xiangya Hospital, Central South University.
      The approval number is 201512538.

PMID- 27878757
TI  - Targeting CCR3 to Reduce Amyloid-beta Production, Tau Hyperphosphorylation, and
      Synaptic Loss in a Mouse Model of Alzheimer's Disease.
AB  - The majority of Alzheimer's disease (AD) patients have a late onset, and chronic
      neuroinflammation, characterized by glial activation and secretion of pro
      inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD.
      The chemokine CCL11 has been shown to be a causative factor of cognitive decline
      in the process of aging, but little is known whether it is involved in the
      pathogenesis of AD. In the present study, we showed that CCR3, the receptor for
      CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal
      neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin
      dependent kinase 5 and glycogen synthase kinase-3beta, associated with elevated
      tau phosphorylation at multiple sites. CCL11 treatment also induced the
      production of Abeta and dendritic spine loss in the hippocampal neuronal
      cultures. All these effects were blocked by the CCR3 specific antagonist,
      GW766994. An age-dependent increase in CCL11, predominantly expressed by the
      activated microglia, was observed in the cerebrospinal fluid of both APP/PS1
      double transgenic mice and wild-type (WT) littermates, with a markedly higher
      level in APP/PS1 double transgenic mice than that in WT littermates. Deletion of
      CCR3 in APP/PS1 double transgenic mice significantly reduced the phosphorylation
      of CDK5 and GSK3beta, tau hyperphosphorylation, Abeta deposition, microgliosis,
      astrogliosis, synaptic loss, and spatial learning and memory deficits. Thus, the
      age-related increase in CCL11 may be a risk factor of AD, and antagonizing CCR3
      may bring therapeutic benefits to AD.

PMID- 27878758
TI  - Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau
      Expression and Phosphorylation: Possible Implications for Tauopathies.
AB  - Public transcriptomic studies have shown that several genes display pronounced
      gender differences in their expression in the human brain, which may influence
      the manifestations and risk for neuronal disorders. Here, we apply a
      transcriptome-wide analysis to discover genes with gender-specific expression and
      significant alterations in public postmortem brain tissue from Alzheimer's
      disease (AD) patients compared to controls. We identify the sex-linked ubiquitin
      specific peptidase 9 (USP9) as an outstanding candidate gene with highly
      significant expression differences between the genders and male-specific
      underexpression in AD. Since previous studies have shown that USP9 can modulate
      the phosphorylation of the AD-associated protein MAPT, we investigate functional
      associations between USP9 and MAPT in further detail. After observing a high
      positive correlation between the expression of USP9 and MAPT in the public
      transcriptomics data, we show that USP9 knockdown results in significantly
      decreased MAPT expression in a DU145 cell culture model and a concentration
      dependent decrease for the MAPT orthologs mapta and maptb in a zebrafish model.
      From the analysis of microarray and qRT-PCR experiments for the knockdown in
      DU145 cells and prior knowledge from the literature, we derive a data-congruent
      model for a USP9-dependent regulatory mechanism modulating MAPT expression via
      BACH1 and SMAD4. Overall, the analyses suggest USP9 may contribute to molecular
      gender differences observed in tauopathies and provide a new target for
      intervention strategies to modulate MAPT expression.

PMID- 27878759
TI  - Loss of Adenylyl Cyclase Type-5 in the Dorsal Striatum Produces Autistic-Like
      Behaviors.
AB  - Autism spectrum disorders (ASDs) are a heterogeneous group of psychiatric illness
      characterized by common core symptoms including sociability deficits and
      stereotyped behaviors. ASD is caused by various genetic and non-genetic factors.
      The genetic effects of autism-related genes are usually global and are presented
      with multiple symptoms, which hamper understanding of the mechanism through which
      the diverse causes of ASD produce common symptoms. In the present study, we
      demonstrate that genetic or molecular disruption of an array of molecular
      networks centered on adenylyl cyclase type-5 (AC5 or ADCY5) in the dorsal
      striatum produces autistic-like behaviors. AC5 knockout (KO) mice exhibit
      increased repetitive behaviors and sociability deficits, the two core domains of
      ASD, and that siRNA-mediated suppression of AC5 within the dorsal striatum is
      sufficient to replicate these behavioral phenotypes. Notably, the autistic-like
      behaviors of AC5 KO mice are rescued by blocking mGluR5 glutamate receptors
      within the dorsal striatum. Furthermore, pharmacological or siRNA-mediated
      inhibition of mGluR3, GluA and GluN glutamate receptors in the dorsal striatum in
      wildtype mice also induces autistic-like behaviors. Optogenetic inhibition of the
      prelimbic cortical neurons projecting to the dorsal striatum in AC5 KO mice
      rescues the deficits in social and object novelty preferences. Our results
      suggest that AC5 mutation produces autistic-like symptoms through the
      upregulation of mGluR5 functions in the dorsal striatum and that the dorsal
      striatum regulated by AC5 is a neural correlate responsible for core ASD
      symptoms.

PMID- 27878760
TI  - Reduced Plasma Levels of 25-Hydroxycholesterol and Increased Cerebrospinal Fluid
      Levels of Bile Acid Precursors in Multiple Sclerosis Patients.
AB  - Multiple sclerosis (MS) is an autoimmune, inflammatory disease of the central
      nervous system (CNS). We have measured the levels of over 20 non-esterified
      sterols in plasma and cerebrospinal fluid (CSF) from patients suffering from MS,
      inflammatory CNS disease, neurodegenerative disease and control patients.
      Analysis was performed following enzyme-assisted derivatisation by liquid
      chromatography-mass spectrometry (LC-MS) exploiting multistage fragmentation (MS
      n ). We found increased concentrations of bile acid precursors in CSF from each
      of the disease states and that patients with inflammatory CNS disease classified
      as suspected autoimmune disease or of unknown aetiology also showed elevated
      concentrations of 25-hydroxycholestertol (25-HC, P < 0.05) in CSF. Cholesterol
      concentrations in CSF were not changed except for patients diagnosed with
      amyotrophic lateral sclerosis (P < 0.01) or pathogen-based infections of the CNS
      (P < 0.05) where they were elevated. In plasma, we found that 25-HC (P < 0.01),
      (25R)26-hydroxycholesterol ((25R)26-HC, P < 0.05) and 7alpha-hydroxy-3-oxocholest
      4-enoic acid (7alphaH,3O-CA, P < 0.05) were reduced in relapsing-remitting MS
      (RRMS) patients compared to controls. The pattern of reduced plasma levels of 25
      HC, (25R)26-HC and 7alphaH,3O-CA was unique to RRMS. In summary, in plasma, we
      find that the concentration of 25-HC in RRMS patients is significantly lower than
      in controls. This is consistent with the hypothesis that a lower propensity of
      macrophages to synthesise 25-HC will result in reduced negative feedback by 25-HC
      on IL-1 family cytokine production and exacerbated MS. In CSF, we find that the
      dominating metabolites reflect the acidic pathway of bile acid biosynthesis and
      the elevated levels of these in CNS disease is likely to reflect cholesterol
      release as a result of demyelination or neuronal death. 25-HC is elevated in
      patients with inflammatory CNS disease probably as a consequence of up-regulation
      of the type 1 interferon-stimulated gene cholesterol 25-hydroxylase in
      macrophages.

PMID- 27878761
TI  - Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults:
      Identification of Novel Risk Loci in African-Americans and European-Americans.
AB  - The human sense of smell decreases with age, and a poor sense of smell are among
      the most important prodromal symptoms of several neurodegenerative diseases.
      Recent evidence further suggests a racial difference in the sense of smell among
      U.S. older adults. However, no genome-wide association study (GWAS) on the sense
      of smell has been conducted in African-Americans (AAs). We performed the first
      genome-wide meta-analysis of the sense of smell among 1979 AAs and 6582 European
      Americans (EAs) from three U.S. aging cohorts. In the AA population, we
      identified nine novel regions (KLF4-ACTL7B, RAPGEF2-FSTL5, TCF4-LOC100505474,
      PCDH10, KIAA1751, MYO5B, MIR320B1-CD2, NR5A2-LINC00862, SALL1-C16orf97) that were
      associated with the sense of smell (P < 5 * 10-8). Many of these regions have
      been previously linked to neuropsychiatric (schizophrenia or epilepsy) or
      neurodegenerative (Parkinson's or Alzheimer's disease) diseases associated with a
      decreased sense of smell. In the EA population, we identified two novel loci in
      or near RASGRP1 and ANXA2P3 associated with sense of smell. In conclusion, this
      study identified several ancestry-specific loci that are associated with the
      sense of smell in older adults. While these findings need independent
      confirmation, they may lead to novel insights into the biology of the sense of
      smell in older adults and its relationships to neuropsychological and
      neurodegenerative diseases.

PMID- 27878764
TI  - The involvement of supratentorial white matter in multiple system atrophy: a
      diffusion tensor imaging tractography study.
AB  - It has been assumed that cognitive disorder and visual-spatial disturbance in
      multiple system atrophy of the predominantly cerebellar type (MSA-C) are
      attributable to degradation of cerebellar function. The purpose of this study was
      to use diffusion tensor imaging (DTI) tractography to determine if patients with
      MSA-C characterized in part by visual-spatial disorders and cognitive disorders
      have changes of the structural connectivity network of nerve fibers, and to
      further describe the structural connectivity network. The study included 20
      patients with MSA-C and 30 age- and sex-matched healthy controls. A 1.5T magnetic
      resonance imaging (MRI) scanner was used to obtain images for DTI tractography.
      Image preprocessing was done by large deformation diffeomorphic metric mapping.
      Whole-brain connectivity analysis was carried out. The patients had decreased
      numbers of long association fibers connecting the right parietal lobe to the
      frontal lobe. The commissural fibers and short association fibers connecting the
      bilateral frontal and occipital lobes and the number of short association fibers
      at the bilateral frontal and occipital region were also decreased significantly.
      The patients had a significant decrease in fiber density in the cerebellum
      compared to the healthy subjects. Our results provide DTI evidence suggesting
      that frontal and occipital white matter is involved in patients with MSA-C. This
      finding may correlate with their clinical symptoms such as cognitive disturbance
      as well as visual-spatial impairment. Therefore, cognitive disturbance and visual
      spatial deficits in MSA-C might not be due to cerebellar lesions only as is
      widely believed but also involve cerebral lesions.

PMID- 27878765
TI  - Primary central nervous system lymphoma of T-cell origin: an unusual cause of
      spinal cord disease.

PMID- 27878766
TI  - The Role of Patient Navigation on Colorectal Cancer Screening Completion and
      Education: a Review of the Literature.
AB  - Although the general assumption is that patient navigation helps patients adhere
      to CRC screening recommendations, concrete evidence for its effectiveness is
      still currently under investigation. The present literature review was conducted
      to explore effectiveness of patient navigation and education on colorectal cancer
      (CRC) screening completion in medically underserved populations. Data collection
      included PubMed, Google Scholar, and Cochrane reviews searches. Study inclusion
      criteria included randomized controlled trials and prospective investigations
      that included an intervention and control group. Case series, brief
      communications, commentaries, case reports, and uncontrolled studies were
      excluded. Twenty-seven of the 36 studies screened for relevance were selected for
      inclusion. Most studies explored the utility of lay and clinic-based patient
      navigation. Others implemented interventions that included tailored messaging,
      and culturally and linguistically appropriate outreach and education efforts to
      meet CRC screening needs of medically underserved individuals. More recent
      studies have begun to conduct cost-effectiveness analyses of patient navigation
      programs that impacted CRC screening and completion. Peer-reviewed publications
      consistently indicate a positive impact of patient navigation programs on CRC
      screening completion, as well have provided preliminary evidence for their cost
      effectiveness.

PMID- 27878763
TI  - Enhancement of Neural Stem Cell Survival, Proliferation, Migration, and
      Differentiation in a Novel Self-Assembly Peptide Nanofibber Scaffold.
AB  - Considerable efforts have been made to combine biologically active molecules into
      the self-assembling peptide in order to improve cells growth, survival, and
      differentiation. In this study, a novel three-dimensional scaffold
      (RADA4GGSIKVAV; R-GSIK) was designed by adding glycine and serine between RADA4
      and IKVAV to promote the strength of the peptide. The cell adhesion, viability,
      proliferation, migration, and differentiation of rat embryonic neural stem cells
      (NSCs) in R-GSIK were investigated and compared to laminin-coated, two
      dimensional, and Puramatrix cultures. The scanning electron microscopy studies of
      the R-GSIK showed an open porous structure and a suitable surface area available
      for cell interaction. R-GSIK promoted the cell adhesion, viability,
      proliferation, and migration compared to the other cultures. In addition, the R
      GSIK enhanced NSCs differentiation into neuronal cells. The NSCs injected in R
      GSIK had a lower glial differentiation rate than in the Puramatrix. The results
      suggest that R-GSIK holds great promise for cell therapies and neuronal tissue
      repair.

PMID- 27878762
TI  - miR Cluster 143/145 Directly Targets Nrl and Regulates Rod Photoreceptor
      Development.
AB  - Retinal histogenesis requires coordinated and temporal functioning of factors by
      which different cell types are generated from multipotent progenitors.
      Development of rod photoreceptors is regulated by multiple transcription factors,
      and Nrl is one of the major factors involved in their fate specification.
      Presence or absence of Nrl at the postnatal stages decides the generation of cone
      photoreceptors or other later retinal cells. This suggests the need for regulated
      expression of Nrl in order to accelerate the generation of other cell types
      during retinal development. We found that miR cluster 143/145, comprising miR-143
      and miR-145, targets and imparts a posttranscriptional inhibition of Nrl.
      Expression of both miRNAs was differentially regulated during retinal development
      and showed least expression at PN1 stage in which most of the rod photoreceptors
      are generated. Downregulation of rod photoreceptor regulators and markers upon
      miR cluster 143/145 overexpression demonstrated that this cluster indeed
      negatively regulates rod photoreceptors. Further, we prove that Nrl positively
      regulates miR cluster 143/145, thus establishing a feedback loop regulatory
      mechanism. This may be one possible mechanism by which Nrl is
      posttranscriptionally regulated to facilitate the generation of other cell types
      in retina.

PMID- 27878767
TI  - Phenobarbital Versus Valproate for Generalized Convulsive Status Epilepticus in
      Adults: A Prospective Randomized Controlled Trial in China.
AB  - OBJECTIVE: Although generalized convulsive status epilepticus (GCSE) is a life
      threatening emergency, evidence-based data to guide initial drug treatment
      choices are lacking in the Chinese population. We conducted this prospective,
      randomized, controlled trial to evaluate the relative efficacy and safety of
      intravenous phenobarbital and valproate in patients with GCSE. METHODS: After the
      failure of first-line diazepam treatment, Chinese adult patients with GCSE were
      randomized to receive either intravenous phenobarbital (standard doses, low rate)
      or valproate (standard). Successful treatment was considered when clinical and
      electroencephalographic seizure activity ceased. Adverse events following
      treatment, as well as the neurological outcomes at discharge and 3 months later,
      were also evaluated. RESULTS: Overall, 73 cases were enrolled in the study.
      Intravenous phenobarbital was successful in 81.1% of patients, and intravenous
      valproate was successful in 44.4% of patients (p < 0.05). The relapse rate of
      status epilepticus within 24 h of receiving phenobarbital (6.7%) was
      significantly lower than that in patients receiving valproate (31.3%), and the
      total number of adverse events did not differ significantly between the two
      groups (p > 0.05). In the phenobarbital group, two patients (5.4%) required
      ventilation and two patients (5.4%) developed serious hypotension. The
      neurological outcomes of the phenobarbital group were generally better than those
      of the valproate group; however, no significant differences were observed between
      phenobarbital and valproate with respect to mortality (8.1 vs. 16.6%) at
      discharge, or mortality (16.2 vs. 30.5%) and post-symptomatic epilepsy (26.3 vs.
      42.8%) at 3-month follow-up. CONCLUSIONS: Intravenous phenobarbital appears to be
      more effective than intravenous valproate for Chinese adult patients with GCSE.
      The occurrence of serious respiratory depression and hypotension caused by
      phenobarbital was reduced by decreasing the intravenous infusion rate; however,
      even at a lower infusion rate than typically used in other institutions,
      intravenous phenobarbital resulted in more serious adverse events than
      intravenous valproate. The better outcomes in the phenobarbital group compared
      with the valproate group suggest that phenobarbital should be considered for the
      early successful treatment of GCSE.

PMID- 27878768
TI  - Congenital forward shoulder with clavicle hypoplasia: surgical lengthening by
      intercalary graft positioning and plate fixation.
AB  - BACKGROUND: Congenital forward shoulder with clavicular hypoplasia is a rare
      disease which can be caused by an alteration of clavicular development in such a
      way that the clavicles are short. Symptoms are often absent; in most cases the
      main problem is represented by the cosmetic implications. There is no general
      consensus about the correct management, and surgery is the only way to correct
      the deformity. MATERIALS AND METHODS: The aim of the study is to describe a new
      surgical treatment in patients with congenital forward shoulder and clavicular
      hypoplasia. In 2010, three patients suffering from bilateral congenital forward
      shoulder were managed surgically by a intercalary graft positioning with plate
      fixation aimed at the elongation of the clavicles. RESULTS: Patients were
      followed by up to 2 years. All the patients treated were satisfied with the
      results, regarding the resolution of mild pain, but especially from the cosmetic
      point of view. CONCLUSION: The intercalary graft positioning was found to be easy
      to perform and allowed an elongation of the clavicles with immediate stability.

PMID- 27878770
TI  - A low-cost method for chromoendoscopy for surveillance in ulcerative colitis.
AB  - The risk of colorectal cancer in Indian patients with long-standing ulcerative
      colitis is high and similar to that in the West. Surveillance for dysplasia in
      these patients is therefore important. Recent studies and guidelines suggest an
      increasing role for chromoendoscopy-guided biopsy in surveillance for dysplasia.
      We report our experience with the technique of chromoendoscopy and an economical
      method of performing it. Reconstituting indigo carmine from a powder form rather
      than the dyes available commercially is a better economical alternative and
      should help make chromoendoscopy the standard of care for dysplasia surveillance
      across the country.

PMID- 27878769
TI  - To what extent residual alveolar ridge can be preserved by implant? A systematic
      review.
AB  - BACKGROUND: It has been reported that the load for (or to) implant-supported
      restoration may lead to bone remodeling as bone resorption and/or formation.
      While many authors supported the process of bone resorption, others elaborated
      bone apposition and increasing bone density close and remote to implant body (or
      fixture). This may suggest the role of the implant to reserve alveolar ridge from
      physiologic/pathologic resorption. The aim of this systematic review was to
      predict to how extend dental implants can preserve the residual alveolar ridge
      based on previous clinical investigations. METHODS: This systematic review based
      on the retrospective and prospective studies, randomized clinical trial, and case
      reports. The process of searching for proposed articles included PubMed, Ovid,
      and Web of Science databases, with specific inclusion and exclusion criterion.
      RESULTS: A total 2139 citations were identified. After expunging the repeated
      articles between databases and application of exclusion and inclusion criteria,
      18 articles were found to meet the topic of this systematic review. Many of the
      articles reported bone preservation with implant-assisted restorations, and the
      rest denoted noticeable bone apposition. CONCLUSION: According to the published
      clinical studies, the behavior of bone remodeling around implant predicts a sort
      of residual alveolar bone preservation.

PMID- 27878771
TI  - Growth hormone deficiency and hypopituitarism in adults after complicated mild
      traumatic brain injury.
AB  - PURPOSE: Traumatic brain injury is considered the main cause of hypopituitarism
      in adults, and GH deficiency appears to be the most frequent pituitary deficit.
      Most of the available studies have included all degrees of severity of trauma. We
      aimed to assess pituitary function and GH deficiency in adult patients at
      different time lengths after complicated mild TBI according to Glasgow Coma
      Scale. We also aimed to evaluate whether mild TBI patients with GH deficiency had
      developed alterations in the glycolipid profile. METHODS: Forty-eight patients
      (34 men and 14 women) with complicated mild TBI were included in the study.
      Twenty-three patients were evaluated at 1 year (Group A) and 25 patients at 5
      years or longer after the injury (Group B). All patients underwent basal hormonal
      evaluation for pituitary function. GH deficiency was investigated by the combined
      test (GH releasing hormone + arginine). The glycolipid profile was also
      evaluated. RESULTS: GH deficiency occurred in 8/23 patients (34.7 %) of Group A
      and in 12/25 patients (48 %) of Group B. In addition, two patients, one in each
      group, showed evidence of central hypothyroidism. Patients with GH deficiency,
      especially in Group A, presented a higher frequency of visceral adiposity and
      adverse metabolic profile as compared to no-GH deficiency patients. CONCLUSIONS:
      Patients examined at 1 year or several years from complicated mild TBI had a
      similarly high occurrence of isolated GH deficiency, which was associated with
      visceral adiposity and metabolic alterations. Our findings suggest that patients
      undergone complicated mild TBI should be evaluated for GH deficiency even after
      several years from trauma.

PMID- 27878772
TI  - Chronic lymphocytic thyroiditis does not influence the risk of recurrence in
      patients with papillary thyroid carcinoma and excellent response to initial
      therapy.
AB  - BACKGROUND: This study evaluated the recurrence in patients with papillary
      thyroid cancer and an excellent response to initial therapy, comparing those with
      and without chronic lymphocytic thyroiditis. METHODS: This was a prospective
      study. Patients who met the following criteria were selected: diagnosis of
      papillary thyroid cancer; submitted to total thyroidectomy followed or not by
      ablation with 131I; and neck ultrasonography without abnormalities, nonstimulated
      thyroglobulina (Tg) <=0.2 ng/ml, and undetectable antithyroglobulin antibodies
      (TgAb) 12-18 months after initial therapy. The patients were divided into two
      groups: group A, with chronic lymphocytic thyroiditis on histology; group B,
      without chronic lymphocytic thyroiditis on histology. RESULTS: Groups A and B
      were similar in terms of sex and age of the patients, characteristics of the
      tumor, tumor-node-metastase stage and risk category. The time of follow-up ranged
      from 24 to 120 months (median 66 months). During follow-up, 5 patients of group A
      (2.6 %) and 9 patients of group B (2 %) developed recurrence (p = 0.77). Patients
      with chronic lymphocytic thyroiditis were more likely to progress to persistently
      borderline TgAb. No patient had positive TgAb (above the reference value) during
      follow-up. Recurrences occurred in 12/588 patients (2 %) with undetectable TgAb
      in all measurements, in 1/32 (3.1 %) with detectable TgAb on some occasion but
      that returned to undetectable spontaneously, and in 1/13 (7.7 %) with
      persistently borderline TgAb. These rates did not differ significantly (p =
      0.25). CONCLUSION: The results of the present study showed the absence of an
      association between chronic lymphocytic thyroiditis and recurrence risk at least
      in patients with an excellent response to initial therapy.

PMID- 27878774
TI  - A model for determination of operational conditions for successful shortcut
      nitrification.
AB  - Accumulation of nitrite in shortcut nitrification is influenced by several
      factors including dissolved oxygen concentration (DO), pH, temperature, free
      ammonia (FA), and free nitrous acid (FNA). In this study, a model based on
      minimum dissolved oxygen concentration (DOmin), minimum/maximum substrate
      concentration (Smin and Smax), was developed. The model evaluated the influence
      of pH (7-9), temperature (10-35  degrees C), and solids retention time (SRT) (5
      days-infinity) on MSC values. The evaluation was conducted either by controlling
      total ammonium nitrogen (TAN) or total nitrite nitrogen (TNN), concentration at
      50 mg N/L while allowing the other to vary from 0 to 1000 mg N/L. In addition,
      specific application for shortcut nitrification-anammox process at 10  degrees C
      was analyzed. At any given operational condition, the model was able to predict
      if shortcut nitrification can be achieved and provide the operational DO range
      which is higher than the DOmin of AOB and lower than that of NOB. Furthermore,
      experimental data from different literature studies were taken for model
      simulation and the model prediction fit well the experiment. For the Sharon
      process, model prediction with default kinetics did not work but the model could
      make good prediction after adjusting the kinetic values based on the Sharon
      specific kinetics reported in the literature. The model provides a method to
      identify feasible combinations of pH, DO, TAN, TNN, and SRT for successful
      shortcut nitrification.

PMID- 27878773
TI  - Ramadan fasting in patients with adrenal insufficiency.
AB  - AIM: The risks of fasting during Ramadan in patients with adrenal insufficiency
      are unknown. The aims of this study were to evaluate these risks in such
      patients, to determine the risk factors and finally to set some recommendations.
      METHODS: It is a cross-sectional study about 180 patients with known and treated
      adrenal insufficiency. The patients responded to a 14-item questionnaire
      concerning their knowledge about the disease and fasting during the last month of
      Ramadan. RESULTS: There were 132 women and 48 men. The mean age was 47.6 +/- 15.0
      years (14-79). One hundred and thirty eight patients (76.7 %) were advised by
      their physician not to fast. Ninety-one patients (50.5 %) tried to fast.
      Complications occurred in 61 cases (67.0 %): asthenia in 88.5 % of cases, intense
      thirst in 32.8 %, symptoms of dehydration in 49.2 % and symptoms of hypoglycaemia
      in 18 %. One patient was hospitalized. Fifty-five patients (60.4 %) were able to
      fast for the whole month. Age, gender, duration of the disease, its primary
      origin, associated hypothyroidism, diabetes mellitus, hypertension or diabetes
      insipidus and daily dose of hydrocortisone did not significantly differ between
      fasters and non-fasters, full-month-fasters and partial-month-fasters, and
      fasters with complications and fasters without complications. The frequency of
      adequate knowledge about the disease was significantly higher in full-month
      fasters vs. partial-month-fasters, and in fasters without complications vs. those
      with complications. CONCLUSION: In patients with adrenal insufficiency, fasting
      can cause complications especially if the level of knowledge about the disease is
      low.

PMID- 27878775
TI  - Bioremoval of priority polycyclic aromatic hydrocarbons by a microbial community
      with high sorption ability.
AB  - The treatment of large volumes of wastewater during oil refining is presently a
      challenge. Bioremediation has been considered an eco-friendly approach for the
      removal of polycyclic aromatic hydrocarbons (PAHs), which are one of the most
      hazardous groups of organic micropollutants. However, it is crucial to identify
      native PAH-removing microorganisms for the development of an effective
      bioremediation process. This study reports the high potential of an anaerobic
      microbial consortium enriched from a petrochemical refinery wastewater to remove
      two priority PAHs-acenaphthene and phenanthrene. Seventy-seven percent of
      acenaphthene was removed within 17 h, whereas phenanthrene was no longer detected
      after 15 h. Bioremoval rates were extremely high (0.086 and 0.156 h-1 for
      acenaphthene and phenanthrene, respectively). The characterization of the
      microbial communities by next-generation sequencing and fluorescence in situ
      hybridization showed that the PAH-removing consortium was mainly composed by
      bacteria affiliated to Diaphorobacter and Paracoccus genera, independently of the
      PAH tested. Moreover, besides biodegradation, biosorption was a relevant
      mechanism involved in the removal of both PAHs, which is an important finding
      since biosorption is less expensive than biodegradation and can be carried out
      with dead biomass. Although biodegradation is the most commonly reported
      biological mechanism for PAH removal, this study demonstrated that biosorption by
      this microbial community may be extremely efficient for their removal. Given the
      outstanding ability of this microbial consortium to quickly remove the compounds
      addressed, it could be further applied for the bioremediation of PAHs in refinery
      wastewaters and other contaminated environments.

PMID- 27878776
TI  - Successive chlorothalonil applications inhibit soil nitrification and
      discrepantly affect abundances of functional genes in soil nitrogen cycling.
AB  - Broad-spectrum fungicide chlorothalonil (CTN) is successively applied into
      intensive agriculture soil. However, the impacts of successive CTN applications
      on soil nitrification and related microorganisms remain poorly understood. A
      microcosm study was conducted to reveal the effects of successive CTN
      applications on soil nitrification and functional genes involved in soil nitrogen
      (N) cycling. The CTN at the dosages of 5 mg kg-1 dry soil (RD) and 25 mg kg-1 dry
      soil (5RD) was successively applied into the test soil at 7-day intervals which
      resulted in the accumulations of CTN residues. After 28 days of incubation, CTN
      residues in the RD and 5RD treatments were 3.14 and 69.7 mg kg-1 dry soil
      respectively. Net nitrification rates in the RD and 5RD treatments were lower
      than that obtained from the blank control (CK). Real-time PCR analysis revealed
      that AOA and AOB amoA gene abundances were significantly decreased by CTN
      applications. Moreover, CTN applications also discrepantly decreased the
      abundances of functional genes involved in soil denitrification, with the
      exception of nosZ gene. Principal component analysis further supported the
      observation that successive CTN applications could result in enhanced ecological
      toxicity.

PMID- 27878777
TI  - Vitamin K supplementation to prevent hemorrhagic morbidity and mortality of
      newborns in India and China.
AB  - BACKGROUND: Vitamin K deficiency bleeding (VKDB) can cause prolonged and bleeding
      (intracranial hemorrhage) among newborns, which can be life-threatening or lead
      to long-term morbidity. The aim of this review article is to reiterate empirical
      evidence to support the argument that vitamin K should be mandatory for newborns
      in India and China, as well as in other countries with a high burden of neonatal
      deaths. DATA SOURCES: Studies were integrated from the PubMed/MEDLINE database
      search, as well as related literature available elsewhere. RESULTS: Both India
      and China have been slow in adopting an effective program for administering
      vitamin K injections to newborns to prevent VKDB-related morbidity and mortality.
      VKDB cases in China and India have shown inadequate attention to routine use of
      vitamin K by injection. CONCLUSIONS: While no reliable data are publicly
      available, the issue of VKDB is at last receiving some attention from the Chinese
      public health system as well as the Indian government. In both countries, routine
      vitamin K administration to newborns would prove to be a cost-effective
      intervention to reduce preventable neonatal morbidity and mortality. VKDB is a
      global neonatal care issue, including countries where parental resistance is
      preventing babies from defense against this life-threatening condition.

PMID- 27878778
TI  - Elevated serum levels of ghrelin and TNF-alpha in patients with cyanotic and
      acyanotic congenital heart disease.
AB  - BACKGROUND: The levels of ghrelin and tumor necrosis factor alpha (TNF-alpha) are
      considered biological markers of congenital heart diseases (CHD). The present
      meta-analysis was conducted to investigate the clinical significance of serum
      levels of ghrelin and TNF-alpha in children with (CHD). METHODS: Chinese and
      English scientific literature databases were searched to retrieve published
      studies relevant to ghrelin, TNF-alpha and CHD. Manual search was additionally
      employed to identify other relevant studies from cross-references. The retrieved
      studies were screened on the basis of our stringent inclusion and exclusion
      criteria to select high quality case-control studies for meta-analysis. RESULTS:
      We initially retrieved 108 published studies (20 in Chinese and 88 in English)
      from database searches. Finally, 6 case-control studies (5 in English and 1 in
      Chinese) were enrolled in our meta-analysis, and contained a total of 160
      cyanotic congenital heart disease (CCHD) patients and 215 acyanotic congenital
      heart disease (ACHD) patients, along with 162 healthy controls. The results of
      meta-analysis showed that serum levels of ghrelin and TNF-alpha in CCHD or ACHD
      children were significantly higher than those in healthy controls. CONCLUSIONS:
      Our meta-analysis results showed that serum levels of ghrelin and TNF-alpha are
      elevated in children with CHD, and could be used as effective biologic markers in
      early diagnosis of CHD.

PMID- 27878779
TI  - Total estimated effective doses from radiologic imaging modalities of children
      with cancer: a single center experience.
AB  - BACKGROUND: Recently, awareness of the cumulative radiation exposure for
      pediatric oncology patients has been increasing, together with increased survival
      rates and longer life expectancy. The aim of our study was to quantify the amount
      of ionising radiation from imaging modalities of pediatric oncology patients.
      METHODS: Eighty-eight patients who were diagnosed with childhood cancer and
      followed up for 5 years between 2004-2014 in our center were included in the
      study. Patients' medical files were reviewed retrospectively for imaging history
      in the first 5 years after diagnosis. Total estimated effective doses from
      radiologic imaging modalities were determined. Also, the basic demographic data,
      histologic type, stage, and outcomes of disease were collected for all patients.
      RESULTS: The individual total estimated effective doses ranged from 8.73 to 167
      mSv, with a median of 62.92 mSv. Computed tomography was the greatest contributor
      of total effective doses. The doses ranged 21.45-113.20 mSv (median: 62.92 mSv)
      in Hodgkin lymphoma, 12.53-167.10 mSv (median: 52 mSv) in non-Hodgkin lymphoma,
      4.13-172.98 mSv (median: 52 mSv) in neuroblastoma, 31-149.89 mSv (median: 63.10
      mSv) in Wilms' tumor, 11.50-73.72 mSv (median: 36.90 mSv) in germ cell tumor,
      26.46-125.86 mSv (median: 80.90 mSv) in other solid tumor and 0.02-13.31 mSv
      (5.25 mSv) in brain tumor subgroup. Twenty-two children (25%) died with
      progressive disease during the 5-year follow-up period. CONCLUSIONS: Similar to
      previous studies, the total estimated effective doses in children with cancer
      have been found various according to diagnosis, stage and clinical course. To
      clarify the harmfull effects of radiation burden, prospective studies should be
      conducted in children with cancer.

PMID- 27878780
TI  - A pilot study using lactulose in management of minimal hepatic encephalopathy in
      children with extrahepatic portal vein obstruction.
AB  - BACKGROUND: Minimal hepatic encephalopathy (MHE) is not associated with overt
      neuropsychiatric symptoms but rather with subtle changes in psychometric and/or
      neurophysiologic tests. We aimed to diagnose MHE in children with extrahepatic
      portal vein obstruction (EHPVO) and to evaluate the effect of lactulose on MHE.
      METHODS: A prospective study was carried out on 30 patients with EHPVO (21 males;
      mean age 10+/-2.5 years). The study was carried out in the Pediatric Hepatology
      Unit, Cairo University Pediatric Hospital, Cairo, Egypt, between 2011 and 2013.
      All patients were subjected to clinical and laboratory assessment,
      neuropsychmetric testing using the arabic version of Wechsler intelligence tests,
      neurophysiological testing by visual electroencephalogram and P300 event related
      potentials (ERP). RESULTS: The prevalence of MHE among children with EHPVO was
      20% (6/30). After randomization to treatment and no-treatment groups using
      lactulose, all tests were repeated after three months. Among four patients with
      MHE who received lactulose, three (75%) improved. On the other hand, one of the
      patients in the no-treatment group developed MHE. Only one patient in the
      treatment arm had to discontinue lactulose because of severe diarrhea.
      CONCLUSIONS: This pilot study revealed that the prevalence of MHE was 20%.
      Improvement on psychometic tests was seen in 75% of our patients (3/4) after
      treatment with lactulose. Lactulose treatment was well tolerated.

PMID- 27878781
TI  - Successful elimination of extended-spectrum beta-lactamase (ESBL)-producing
      nosocomial bacteria at a neonatal intensive care unit.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative
      bacteria are highly dangerous to neonates. At our Neonatal Intensive Care Unit
      (NICU), the presence of these bacteria became so threatening in 2011 that
      immediate intervention was required. METHODS: This study was conducted during a
      nearly two-year period consisting of three phases: retrospective (9 months),
      educational (3 months) and prospective (9 months). Based on retrospective data
      analysis, a complex management plan was devised involving the introduction of the
      INSURE protocol, changes to the antibiotic regimen, microbiological screening at
      short intervals, progressive feeding, a safer bathing protocol, staff hand
      hygiene training and continuous monitoring of the number of newly infected and
      newly colonized patients. During these intervals, a total of 355 patients were
      monitored. RESULTS: Both ESBL-producing Enterobacter cloaceae and Klebsiella
      pneumoniae were found (in both patients and environmental samples). In the
      prospective period a significant reduction could be seen in the average number of
      both colonized (26/167 patients; P=0.029) and infected (3/167 patients; P=0.033)
      patients compared to data from the retrospective period regarding colonized
      (72/188 patients) and infected (9/188 patients) patients. There was a decrease in
      the average number of patient-days (from 343.72 to 292.44 days per months),
      though this difference is not significant (P=0.058). During the prospective
      period, indirect hand hygiene compliance showed a significant increase (from the
      previous 26.02 to 33.6 hand hygiene procedures per patient per hospital day,
      P<0.001). CONCLUSION: Colonizations and infections were rolled back successfully
      in a multi-step effort that required an interdisciplinary approach.

PMID- 27878782
TI  - Trajectory of cause of death among brought dead neonates in tertiary care public
      facilities of Pakistan: A multicenter study.
AB  - BACKGROUND: Considering the fact that Pakistan is amongst the countries with very
      high neonatal mortality rates, we conducted a research study to determine the
      possible causes and characteristics of neonates presenting dead to the emergency
      department of tertiary public health care facilities of Pakistan using verbal
      autopsies. METHODS: A descriptive case series study was conducted in emergency
      department/pediatrics ward/neonatal ward/nursery unit of ten tertiary care public
      health facilities, situated in seven major cities of Pakistan from November, 2011
      to June, 2013. Precoded verbal autopsy proforma was used to collect information
      regarding cause of death, family narratives and other associated risks
      accountable for pathway to mortality. RESULTS: We identified 431 neonates
      presenting dead to the emergency department (238 males and 193 females). Sepsis
      (26.7%), birth asphyxia (18.8%) and persistent pulmonary arrest (17.2%) were main
      primary causes of brought death. Around 72% brought dead neonates were referred
      from doctors/health care facilities and more than 28% caregivers mentioned that
      they were not informed about the diagnosis/ailment of their deceased newborn.
      CONCLUSIONS: Findings of our study suggest that infectious disease remains the
      main primary cause of neonatal mortality. Underweight in newborns (64%) was
      estimated as a leading associated risk. Delays in referrals to respective health
      care facility enlightened the concern of sub-standard prerequisites of neonatal
      care that could be one of the major contributing risk factor of high mortality
      rates.

PMID- 27878783
TI  - Prediction of significant hyperbilirubinemia in term neonates by early non
      invasive bilirubin measurement.
AB  - BACKGROUND: Neonatal jaundice is a common problem. We evaluated the utility and
      best cut-off values of 24-and 48-hour transcutaneous bilirubin indices (TcBI) in
      predicting subsequent significant hyperbilirubinemia and evaluated various
      associated maternal and fetal risk factors. METHODS: TcBI at 24 and 48 hours and
      serum bilirubin levels at 72 hours of age were obtained for healthy, term,
      appropriate for gestational age neonates. Neonates with prematurity, birth weight
      <2500 g, ABO or Rh incompatibility, onset of clinical jaundice <24 hours,
      clinical suspicion of septicemia, positive pressure ventilation at birth,
      admission in neonatal intensive care unit and contraindications for BiliChek were
      excluded. Twently-four and 48-hour TcB indices were assessed as predictors of
      subsequent hyperbilirubinemia, defined as serum bilirubin >17 mg/dL after 72
      hours of life and various cut-offs, and were evaluated by calculating
      sensitivity, specificity and predictive values. RESULTS: Of 500 newborns, 4.6%
      had significant hyperbilirubinemia, 27% had TcBI (mg/dL) <5 at 24 hours, and
      27.4% had TcBI <8 at 48 hours. None of them had subsequent hyperbilirubinemia
      (100% negative predictive value). The percentage of newborns with subsequent
      hyperbilirubinemia increased from 3.4% to 13.2% as their 24-hour TcBI increased
      from 6 to above 9 mg/dL and from 4.2% to 7.4% as their 48-hour TcBI increased
      from 8 to above 11 mg/dL. The best cut-off value was TcBI (mg/dL) 7 (odd
      ratio=4.86, 95% confidence interval: 1.66-15.22) at 24 hours and 10 (odd
      ratio=2.87, 95% confidence interval: 1.04-8.29) at 48 hours. Area under the
      receiver operating characteristic curve for 24- and 48-hour measurements was
      0.750 and 0.715, respectively. Maternal premature rupture of membranes, deep
      transverse arrest, post-date pregnancy, and fetal distress were significant risk
      factors for hyperbilirubinemia. CONCLUSIONS: Twenty-four and 48-hour TcB indices
      are good predictors of subsequent hyperbilirubinemia. Twenty-four-hour TcBI had
      better predictive ability than 48-hour TcBI.

PMID- 27878784
TI  - A population-based study of prevalence of Down syndrome in Southern Thailand.
AB  - BACKGROUND: Down syndrome (DS) is the most common chromosomal disorder that
      causes mental retardation. In 2009, a population-based birth defects study was
      implemented in three provinces in southern Thailand. This study aimed to
      determine the prevalence of DS in the studied regions, and the proportion of DS
      fetuses detected by prenatal screening. METHODS: Data were obtained from a
      population-based surveillance study undertaken during 2009-2013. Entries in the
      birth defects registry included live births, stillbirths after 24 weeks
      gestational age, and terminations of pregnancy following prenatal diagnosis.
      Infants with clinical characteristics of DS had a chromosomal study to make a
      definite diagnosis. RESULTS: Of the total 186 393 births recorded during the
      study period, 226 DS cases were listed, giving a prevalence of 1.21 per 1000
      births [95% confidence interval (CI) 1.05-1.37]. The median maternal age was 36.5
      years with a percentage of maternal age >=35 years of 60.6%. Seventy-seven cases
      (34.1% of all cases) were diagnosed prenatally and these pregnancies were
      terminated. The prevalence of DS per 1000 births was significantly higher in
      older women, from 0.47 (95% CI 0.28-0.67) in mothers aged <30 years to 0.88 (95%
      CI 0.59-1.17) in mothers 30-<35 years (P<0.01), and to 4.74 (95% CI 3.95-5.53) in
      mothers >=35 years (P<0.001). CONCLUSIONS: The prevalence of DS significantly
      increased with maternal age. About 35% of DS cases were detected prenatally and
      later terminated. Hence, examining only registry live births will result in an
      inaccurate prevalence rate of DS.

PMID- 27878785
TI  - Lesions requiring wound management in a central tertiary neonatal intensive care
      unit.
AB  - BACKGROUND: Most of the skin disorders that occur in neonatal intensive care
      units are due in part to the immaturity and vulnerability of the neonatal skin.
      Various iatrogenic diagnostic and therapeutic procedures are also conducive to
      iatrogenic damage. This study was to review the neonates admitted to our neonatal
      intensive care unit who needed wound management, and to assess the most common
      skin injuries and wounds, and their aetiology. METHODS: Data were extracted from
      medical records of neonates who needed wound management in our Neonatal Intensive
      Care Unit between January 31, 2012 and January 31, 2013. Information about
      gestational age, sex, birth weight, area of involvement, wound aetiology, and
      therapy were collected. RESULTS: Among the 211 neonates observed, wound
      management was required in 10 cases of diaper dermatitis, 7 epidermal stripping,
      6 extravasation injuries, 5 pressure ulcers, 1 surgical wound and infection, 1
      thermal burn, and 5 other lesions. CONCLUSIONS: International guidelines in
      neonatal wound care practice are not available, and further research concerns are
      clearly needed. Dressings and antiseptic agents should be chosen with great care
      for application to neonates, with particular attention to the prevention of
      adverse events in this sensitive population. Team work among dermatologists,
      neonatologists and nurses is crucial for the successful treatment of neonates.

PMID- 27878787
TI  - Interdisciplinary decision-making and treatment of intracranial aneurysms in the
      era of complementary microsurgical and endovascular techniques.
AB  - Rupture of an intracranial aneurysm is a life-threatening event. Only one third
      of intracranial aneurysms rupture during a patient's lifetime. Accurate markers
      that predict which intracranial aneurysms rupture and which do not are currently
      lacking in routine clinical practice. Therefore, the treatment decision is a
      careful balance between the natural history of the intracranial aneurysm and the
      risk of intervention based on aneurysm- and patient-specific risk factors. Many
      of these risk factors are also used to determine the modality of intervention. In
      this review, the authors discuss the interdisciplinary decision-making process
      and treatment approach in the era of complementary techniques for intracranial
      aneurysm obliteration.

PMID- 27878786
TI  - Enhancing poly(3-hydroxyalkanoate) production in Escherichia coli by the removal
      of the regulatory gene arcA.
AB  - Recombinant Escherichia coli is a desirable platform for the production of many
      biological compounds including poly(3-hydroxyalkanoates), a class of naturally
      occurring biodegradable polyesters with promising biomedical and material
      applications. Although the controlled production of desirable polymers is
      possible with the utilization of fatty acid feedstocks, a central challenge to
      this biosynthetic route is the improvement of the relatively low polymer yield, a
      necessary factor of decreasing the production costs. In this study we sought to
      address this challenge by deleting arcA and ompR, two global regulators with the
      capacity to inhibit the uptake and activation of exogenous fatty acids. We found
      that polymer yields in a DeltaarcA mutant increased significantly with respect to
      the parental strain. In the parental strain, PHV yields were very low but
      improved 64-fold in the DeltaarcA mutant (1.92-124 mg L-1) The DeltaarcA mutant
      also allowed for modest increases in some medium chain length polymer yields,
      while weight average molecular weights improved by approximately 1.5-fold to 12
      fold depending on the fatty acid substrate utilized. These results were supported
      by an analysis of differential gene expression, which showed that the key genes
      (fadD, fadL, and fadE) encoding fatty acid degradation enzymes were all
      upregulated by 2-, 10-, and 31-fold in an DeltaarcA mutant, respectively.
      Additionally, the short chain length fatty acid uptake genes atoA, atoE and atoD
      were upregulated by 103-, 119-, and 303-fold respectively, though these values
      are somewhat inflated due to low expression in the parental strain. Overall, this
      study demonstrates that arcA is an important target to improve PHA production
      from fatty acids.

PMID- 27878789
TI  - Regional sociocultural differences as important correlate of physical activity
      and sedentary behaviour in Swiss preschool children.
AB  - QUESTION: Regional differences in physical activity in school-aged children and
      adults even within one country with the same political and health care system
      have been observed and could not be explained by sociodemographic or individual
      variables. We analysed whether such differences were already present in preschool
      children. METHODS: Swiss children from 84 childcare centres in five cantons
      (Aargau, Bern, Fribourg, Vaud, Zurich) comprising about 50% of the population of
      the country participated. Physical activity was quantified with accelerometers
      (ActiGraph, wGT3X-BT) and potential correlates were assessed with measurements at
      the childcare centre or questionnaires. Mixed regression models were used to test
      associations between potential correlates of total physical activity (TPA),
      moderate-to-vigorous physical activity (MVPA), light physical activity (LPA) or
      sedentary behaviour with a special focus on regional differences. RESULTS: 394 of
      476 children (83%) provided valid physical activity data (at least 2 weekdays and
      1 weekend day with 10 h recording; mean age 3.9 +/- 0.7 years, 54% boys) with 26%
      and 74% living in the French- and German-speaking parts of Switzerland,
      respectively. Days consisted of (mean +/- standard deviation) 1.5 +/- 0.5 h MVPA,
      5.0 +/- 0.6 h LPA, and 6.3 +/- 0.8 h sedentary behaviour with an average of 624
      +/- 150 counts/min TPA. TPA and MVPA (but not sedentary behaviour or LPA)
      increased with age, were higher in boys and children with better motor skills.
      Despite controlling for individual characteristics, familial factors and
      childcare exposure, children from the French-speaking part of Switzerland showed
      13% less TPA, 14% less MVPA, 6% less LPA and 8% more sedentary behaviour than
      German-speaking children. CONCLUSION: Beside motor skills and non-modifiable
      individual factors, the regional sociocultural difference was the most important
      correlate of phyical activity and sedentary behaviour. Therefore, regionally
      adapted public health strategies may be needed.

PMID- 27878788
TI  - Sun protective behaviour and sunburn prevalence in primary and secondary
      schoolchildren in western Switzerland.
AB  - AIMS OF THE STUDY: Although solar overexposure during childhood and adolescence
      increases the risk of melanoma, determinants of sunburn and sun protective
      behaviours of Swiss children have scarcely been explored. We investigated sunburn
      occurrence and sun protective behaviours of schoolchildren in western
      Switzerland, the region with the highest incidence of melanoma in Europe.
      MATERIAL AND METHODS: Self-reported questionnaires were administered during
      regular classes to pupils in 5th (primary school, n = 431), 8th and 11th grades
      (secondary school, n = 837) in the 18 public schools of La Chaux-de-Fonds.
      Descriptive statistics and multivariate logistic regression analyses were
      performed to assess predictors of sunburns and of three sun protective behaviours
      (sunscreen, shade, wear of covering clothes). RESULTS: Response rate was 91%.
      Sunburn prevalence over the preceding year was high (60% at least one sunburn,
      30% at least two, 43% at least one severe sunburn). Younger age, fair skin,
      regular sunscreen use, higher sun-related knowledge and preference for a tanned
      skin were predictors of sunburn. Sunscreen was the most used protective measure
      (69%), followed by seeking shade (33%) and wearing long-sleeved shirts (32%).
      Decline in all protective measures was observed in older pupils and those with
      pro-tan attitudes. The wear of covering clothes was significantly associated with
      sunscreen use and seeking shade. Parental encouragement favoured sunscreen use
      and wearing of protective clothes. CONCLUSIONS: Sunscreen use as a last
      protective barrier against ultraviolet radiation should be better emphasised in
      prevention campaigns targeting children and adolescents. Multi-faceted
      interventions, including role models, parents and peers should help to improve
      children's sun protective behaviours.

PMID- 27878790
TI  - Additional malignancies in patients with neuroendocrine tumours: analysis of the
      SwissNET registry.
AB  - PRINCIPLES: Neuroendocrine neoplasms (NENs) are believed to be associated with an
      increased risk for additional malignancies (AMs). We aimed to (1) assess the
      occurrence of AM in NEN patients (2) investigate the characteristics and temporal
      relationship of NEN patients with and without AM. METHODS: The SwissNET registry
      has prospectively documented patients with NEN since 2008, covering the entire
      area of Switzerland. Clinical characteristics, functionality, location and
      histology of NEN as well as survival of all consecutive patients were retrieved.
      The characteristics of the AM (location, histology, time point of diagnosis in
      relation to diagnosis of NEN) were extracted. RESULTS: Out of 934 patients, 193
      patients (21%) presented with AMs. There was no statistically significant
      difference with regard to location, functionality and grading (G1-G3) between the
      NEN patients with and without AM. AMs were diagnosed synchronously (+/-3 months),
      before (>-3 months) and after (>+3 months) diagnosis of NEN in 82 (42%), 96 (50%)
      and 13 (7%) patients, respectively. Location of NEN correlated with the
      anatomical origin of the AM. Age- and gender- corrected survival was not
      significantly different between NEN patients with and without AM. CONCLUSION: The
      prevalence of AM in NEN is high. The comparable characteristics with regard to
      functionality and grading in the NEN cohorts with and without AM and the similar
      location of AM and NEN suggest a selection bias towards frequent imaging
      procedures in NEN patients with AM.

PMID- 27878791
TI  - New concepts in the management of dyslipidaemiaa.
AB  - Recently, the European Society of Cardiology (ESC) and the European
      Atherosclerosis Society (EAS) published a consensus paper giving guidance on the
      definition and management of statin-associated muscle symptoms (SAMS), as well as
      the use of proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors in very
      high-risk patients. The occurrence of SAMS can have a major negative impact on
      treatment adherence and, consequently, on the prognosis of cardiovascular
      diseases. In addition, both the ESC guidelines on the prevention of
      cardiovascular disease (CVD) in clinical practice with sections addressing global
      strategies to minimise the burden of CVD at population and individual levels, and
      the 2016 ESC/EAS guideline for the management of dyslipidaemias, focus on
      evaluation and treatment of SAMS. The release of these guidelines was a source of
      great interest to clinicians, as new emergent therapies, such as the PCSK9
      inhibitors, have been approved for the treatment of dyslipidaemias: recently,
      both the US Food and Drugs Administration (FDA) and the European Medicines Agency
      (EMA) approved the use of PCSK9 inhibitors as add-ons for the treatment of
      hypercholesterolaemia in cases where low-density lipoprotein cholesterol (LDL-C)
      target levels could not be reached with maximum tolerated statin doses alone, or
      instead of statins in the event of SAMS. Because of the relatively high cost of
      these new therapies, physicians need to justify the use of PCSK9 inhibitors by
      demonstrating that their high-risk patients' LDL-C levels have remained high (1)
      despite a well-conducted, but insufficiently effective high-intensity statin
      therapy (e.g. rosuvastatin 10-20 mg or atorvastatin 40-80 mg), or (2) in the
      event of the patient developing side effects, in particular severe SAMS, during
      treatment with at least three statins. In addition to SAMS, the use of PCSK9
      inhibitors may be considered in patients with documented atherosclerotic
      cardiovascular disease or in patients with familial hypercholesterolaemia and
      poorly controlled LDL-C under the combination of maximum tolerated stain and
      ezetimibe.

PMID- 27878792
TI  - Astrocyte power fuels neurons during stroke.

PMID- 27878793
TI  - Novel cases of amyotrophic lateral sclerosis after treatment of cerebral
      arteriovenous malformationss.
AB  - Previous case studies reported nine patients with cerebral arteriovenous
      malformations (AVM) who developed amyotrophic lateral sclerosis (ALS) after AVM
      embolisation. Here, we describe three novel cases of ALS which developed 13-34
      years after treatment, including embolisation, of cerebral AVM. This study
      provides further arguments supporting the thesis that embolisation of cerebral
      AVM might influence the risk of later ALS development.

PMID- 27878794
TI  - Varicosities of the lower extremity, new approaches: cosmetic or therapeutic
      needs?
AB  - Varicose veins of the lower extremity (VVLE) are a frequently encountered
      vascular disorder in the general population. The general view that VVLE are a non
      serious disease with primarily aesthetic impact is a common misconception, as the
      disease can have a significant negative impact on generic and disease-specific
      quality of life. Further, VVLE may be associated with potentially threatening
      clinical conditions, such as chronic venous ulceration, venous thromboembolism
      and haemorrhage from ruptured varicose veins. In the case of symptomatic varicose
      veins, in the presence of advanced lower limb skin changes or when venous
      complications occur, a referral for dedicated evaluation by the vascular medicine
      specialist is recommended. The initial diagnostic test of choice to detect the
      extent of the varicose disease and to plan treatment is duplex ultrasound.
      Traditionally, compression therapy, surgical high ligation and stripping of the
      truncal veins have been considered standard of care for VVLE. Driven by the aim
      to reduce surgical trauma and improve the long-term effectiveness, minimally
      invasive treatment options have been developed in the last two decades, namely
      endovascular vein ablation techniques (EVA). Endovenous laser ablation and
      radiofrequency ablation have been established as first-line treatments for
      varicose veins associated with axial reflux on the basis of the most recent
      international guidelines. For practical purposes and depending on the concrete
      clinical situation, the various EVA and surgical techniques are often combined,
      leading to multimodal varicose vein therapy management. Knowledge of the
      different techniques is of utmost importance for the vascular medicine
      specialist. The purpose of this article is to provide an overview of the new EVA
      techniques and to elucidate the different therapeutic strategies for VVLE.

PMID- 27878795
TI  - Transcutaneous versus blood carbon dioxide monitoring during acute noninvasive
      ventilation in the emergency department - a retrospective analysis.
AB  - QUESTIONS UNDER STUDY: Transcutaneous measurement of carbon dioxide (PtCO2) has
      been suggested as an alternative to invasively obtained PaCO2 for the monitoring
      of patients with hypercapnic respiratory failure during noninvasive ventilation
      (NIV). Current data on monitoring in hypoxaemic respiratory failure are scarce
      and show conflicting results in hypercapnic patients in the emergency department.
      METHODS AND SETTING: We performed a retrospective comparison of real-time PtCO2
      (SenTec Digital Monitor) and arterial/venous carbon dioxide tension (PaCO2/PvCO2)
      measurements in patients with severe hypoxaemic and/or hypercapnic respiratory
      failure during NIV. Agreement between PtCO2 and PaCO2/PvCO2 was the primary
      endpoint. Bland-Altman analysis and linear regression were used. RESULTS: 102
      patients had at least one matched measurement of PtCO2 and PaCO2/PvCO2. For
      patients with arterial blood gas analysis, the mean difference was 0.46 kPa at
      baseline (95% confidence interval [CI] 0.23 to 0.60, limits of agreement 95% CI 
      0.54 to 1.45) and 0.12 kPa after NIV (95% CI -0.04 to 0.29, limits of agreement
      95% CI: -0.61 to 0.86). The linear regression analysis found a correlation R2 of
      0.88 (p <0.001) at baseline and an R2 of 0.99 (p <0.001) after initiating NIV.
      For patients with venous blood gas analysis, the mean difference was 0.64 kPa at
      baseline (95% CI 0.04 to 1.24, limits of agreement 95% CI -0.72 to 2) and 0.80
      kPa after NIV (95% CI 0.51 to 1.10, limits of agreement 95% CI 0.29 to 1.32), R2
      0.78 (p <0.001) at baseline and R2 0.91 (p <0.001) after initiating NIV. A
      PaCO2/PvCO2 >8 kPa was associated with a lesser degree of agreement between the
      levels of PtCO2 and PaCO2/PvCO2 (p <0.001). CONCLUSION: Transcutaneous PCO2
      monitoring shows a good concordance with PaCO2 and is a reliable, feasible,
      patient-friendly and safe alternative to repeated blood gas analysis for patients
      with severe hypoxaemic and/or hypercapnic respiratory failure receiving emergency
      NIV in the emergency department. An initial blood gas analysis to evaluate the
      respiratory and metabolic state and to rule out a significant discrepancy
      compared with the transcutaneous measurement is recommended.

PMID- 27878796
TI  - Patent foramen ovale: a novel cardiovascular risk factor in patients with sleep
      disordered breathing and high altitude dwellers?
AB  - Diseases associated with chronic hypoxaemia are a leading cause of morbidity and
      mortality in Western countries. Epidemiological data indicate that cardiovascular
      diseases contribute substantially to this problem, but the underlying mechanisms
      are incompletely understood. Sleep disordered breathing and high altitude
      exposure are frequent conditions associated with hypoxaemia. Recent evidence
      suggests that in these conditions the concomitant presence of a patent foramen
      ovale plays an important pathogenic role. For example, in patients with
      obstructive sleep apnoea the presence of a patent foramen ovale is associated
      with more severe sleep disordered breathing, nocturnal oxygen desaturation,
      generalised endothelial dysfunction and arterial hypertension. After patent
      foramen ovale closure, both sleep disordered breathing and cardiovascular
      phenotype improve, suggesting the existence of a possible causal link. During
      short-term high altitude exposure, the presence of a patent foramen ovale, by
      aggravating altitude-induced hypoxaemia, facilitates exaggerated pulmonary
      hypertension. Interestingly, there is increasing evidence showing that in high
      altitude dwellers a patent foramen ovale also alters the cardiovascular
      phenotype. In this article we will summarise recent evidence demonstrating how a
      patent foramen ovale alters the cardiovascular phenotype and increases
      cardiovascular risk in patients with sleep disordered breathing and high-altitude
      dwellers.

PMID- 27878797
TI  - Choosing wisely at the end of life: the crucial role of medical indication.
AB  - At the end of life, several treatments are administered routinely that lack
      medical indication and may cause significant harm to patients. Examples include
      artificial hydration and oxygen therapy in the dying phase, as well as enteral
      nutrition in advanced dementia. Medical indication is defined as the
      appropriateness of a therapeutic or diagnostic measure in the patient's concrete
      clinical situation, in light of the best available evidence. The decision about
      the absence or presence of a medical indication is a core competence of
      physicians. They have no obligation to perform or even mention measures that are
      not indicated. The decision about medical indication is a clinical compound
      decision, composed of both a factual, evidence-based judgement and a value
      judgement, which should always be patient-centred. Acknowledging the crucial role
      of medical indication in clinical decision making in medicine generally and at
      the end of life specifically opens up ways of enhancing patient-physician
      communication by clarifying roles, responsibilities and competencies. This may
      facilitate preventing overtreatment, improving patient wellbeing, and realising
      the patients' goals of care.

PMID- 27878798
TI  - How can patients and their physicians contribute to an outbreak investigation?
      Experiences from a nationwide listeriosis outbreak in Switzerland.
AB  - QUESTIONS UNDER STUDY/PRINCIPLES: Gathering patient information to contain an
      outbreak of Listeria monocytogenes is difficult because of the patients' severe
      illness or death. Extending the range of interviewees to acquire epidemiological
      data can thus be important to maximise information. METHODS: We built the current
      analysis on a case-case outbreak investigation conducted during a Swiss
      listeriosis outbreak between 30 January and 11 May 2014, including 31 patients
      with confirmed L. monocytogenes infection. We interviewed treating physicians and
      patients or their next of kin to gather information on clinical aspects, eating
      habits and food consumption. We compared the different information sources with
      regards to their potential to provide specific, complete and rapid information on
      the affected population and their food consumption history. RESULTS: We obtained
      a 100% response rate among physicians, providing detailed information on the
      affected population by describing health status, underlying conditions, and signs
      and symptoms. Detailed information on food history could not be obtained from
      physicians, making the information vague and unspecific. Less than 50% of
      patients could be interviewed, limiting our information base. Nevertheless,
      patient information on the food history was sufficiently detailed and helped to
      identify the outbreak source CONCLUSIONS: Outbreak investigation teams confronted
      with limited information from patients and with small numbers of cases can
      enhance information on the affected population and the outbreak source by
      combining information from physicians and patients. Physicians provided
      comprehensive information on signs and symptoms, underlying conditions and the
      general health status. Patients remain vital to provide detailed information on
      the food consumption history.

PMID- 27878799
TI  - Microsurgery robots: addressing the needs of high-precision surgical
      interventions.
AB  - Robotics has a significant potential to enhance the overall capacity and
      efficiency of healthcare systems. Robots can help surgeons perform better quality
      operations, leading to reductions in the hospitalisation time of patients and in
      the impact of surgery on their postoperative quality of life. In particular,
      robotics can have a significant impact on microsurgery, which presents stringent
      requirements for superhuman precision and control of the surgical tools.
      Microsurgery is, in fact, expected to gain importance in a growing range of
      surgical specialties as novel technologies progressively enable the detection,
      diagnosis and treatment of diseases at earlier stages. Within such scenarios,
      robotic microsurgery emerges as one of the key components of future surgical
      interventions, and will be a vital technology for addressing major surgical
      challenges. Nonetheless, several issues have yet to be overcome in terms of
      mechatronics, perception and surgeon-robot interfaces before microsurgical robots
      can achieve their full potential in operating rooms. Research in this direction
      is progressing quickly and microsurgery robot prototypes are gradually
      demonstrating significant clinical benefits in challenging applications such as
      reconstructive plastic surgery, ophthalmology, otology and laryngology. These are
      reassuring results offering confidence in a brighter future for high-precision
      surgical interventions.

PMID- 27878800
TI  - A single-centre experience of the implementation of adrenal vein sampling
      procedure: the impact on the diagnostic work-up in primary aldosteronism.
AB  - BACKGROUND: Primary aldosteronism is one of the most common causes of secondary
      hypertension. Adrenal vein sampling (AVS) remains a "gold standard" procedure in
      differentiation between unilateral (adenoma) and bilateral (hyperplasia) disease.
      AIM: The aim of this study was to present our single-centre experience in
      establishing and implementating the AVS procedure. METHODS: All patients had
      primary aldosteronism confirmed in a salt-infusion test. AVS was performed
      sequentially during a continuous intravenous infusion of cosyntropin and was
      preceded by multislice contrast-enhanced computed tomography (CT) examination of
      adrenal glands performed a few weeks before AVS in the majority of patients. AVS
      was regarded as successful if the ratio of each adrenal vein cortisol to inferior
      vena cava cortisol levels (selectivity index [SI]) was higher than 3.0. In the
      case of failure, a second attempt was considered in a few weeks. Patients were
      divided into four groups according to the order of the procedure by quartiles.
      RESULTS: Between 31 May, 2012 and 5 May, 2016, AVS was performed in 124 patients
      (69% males, aged 55.3 +/- 10.3 years) and was successful in 120 (96.8%) patients.
      All failed cases were due to the failure of cannulation of the right adrenal
      vein. The first-attempt success rate was 94.3% (117 of 124 patients) and
      increased from 83.9% in the first 31 patients to 100% in the last 31 patients.
      Similarly, the overall success rate increased from 93.5% to 100%. The right SI
      was significantly higher than the left one (26.4 vs. 11.0, p < 0.0001). Both
      indices did not differ across quartiles of patients. No complications occurred
      during the procedure. CONCLUSIONS: The AVS procedure, preceded by adrenal CT, may
      be implemented into daily diagnostic practice safely with an excellent success
      rate.

PMID- 27878801
TI  - The effect of strength training on quality of prolonged basic cardiopulmonary
      resuscitation.
AB  - BACKGROUND: Providing high-quality chest compressions and rescue breaths are key
      elements in the effectiveness of cardio-pulmonary resuscitation. AIM: To
      investigate the effects of a strength training programme on the quality of
      prolonged basic cardiopulmonary resuscitation on a manikin. METHODS: This was a
      quasi-experimental trial. Thirty-nine participants with prior basic life support
      knowledge were randomised to an experimental or control group. They then
      performed a test of 10 min of chest compressions and mouth-to-mouth ventilation
      on manikins equipped with a skill reporter tool (baseline or test 1). The
      experimental group participated in a four-week strength training programme
      focused on the muscles involved in chest compressions. Both groups were
      subsequently tested again (test 2). RESULTS: After training, the experimental
      group significantly increased the mean depth of compression (53.7 +/- 2.3 mm vs.
      49.9 +/- 5.9 mm; p = 0.003) and the correct compression fraction (68.2 +/- 21.0%
      vs. 46.4 +/- 29.1%; p = 0.004). Trained subjects maintained chest compression
      quality over time better than the control group. The mean tidal volume delivered
      was higher in the experimental than in the control group (701.5 +/- 187.0 mL vs.
      584.8 +/- 113.6 mL; p = 0.040) and above the current resuscitation guidelines. In
      test 2, the percentage of rescue breaths with excessive volume was higher in the
      experi-mental group than in the controls (31.5 +/- 19.6% vs. 15.6 +/- 13.0%; p =
      0.007). CONCLUSIONS: A simple strength training programme has a significant
      impact on the quality of chest compressions and its maintenance over time.
      Additional training is needed to avoid over-ventilation of potential patients.

PMID- 27878802
TI  - Improvement of quality of life following transcatheter aortic valve implantation
      in the elderly: a multi-centre study based on the Polish national TAVI registry.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an effective
      therapeutic method for elderly high-risk patients with symptomatic severe aortic
      stenosis, not eligible for surgical treatment. AIM: The aim of the study was to
      evaluate short-term changes in elderly people's quality of life following TAVI,
      based on the POL-TAVI registry. METHODS: One hundred and eighty-four
      octogenarians' and nonagenarians' samples from the POL-TAVI database were
      included in the study. The quality of life status was assessed with EQ-5D-3L
      questionnaire at baseline and after one-month follow-up. RESULTS: The mean of
      patients' age was 84 (80-93) years. Logistic EuroSCORE mean was 19.83% (3.48
      83.94%), and transaortic mean gradient was 54.99 (19.0-149.0) mm Hg. At baseline,
      up to 24.50% of patients declared severe problems in performing usual activities.
      13.60% felt extreme pain or discomfort; 9.80% were unable to wash and dress by
      themselves; 8.20% were extremely anxious or depressed; and 7.10% of the patients
      in the study were confined to bed. After 30 days the percentage of patients
      declaring severe problems in each dimension did not exceed 4.00%. The comparison
      between quality of life data at baseline and after one-month follow-up showed a
      significant improvement in each of five dimensions: mobility, self-care, usual
      activities, pain/discomfort, and anxiety/depression (p < 0.001). Patients'
      quality of life was increasing regardless of gender (female vs. male), the type
      of anaesthesia (general vs. local), and the type of procedure (TA vs. TF).
      CONCLUSIONS: Short-term quality of life in the elderly subjects was significantly
      improved after one-month follow-up following TAVI.

PMID- 27878803
TI  - Tissue Doppler echocardiography detects subclinical left ventricular dysfunction
      in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO
      multicentre study.
AB  - BACKGROUND: Colorectal cancer (CRC) is the second most common cancer in women and
      the third in men in Poland. The role of chemotherapy (CTX) depends on the stage
      of CRC: adjuvant CTX is a standard treatment in stage III and should also be
      considered in stage II with risk factors. AIM: The aim of the paper was to assess
      the cardiovascular consequences of CTX in CRC enrolled to the ONCOECHO
      multicentre study (2012-2014). To identify potential cardiotoxicity, we focused
      on myocardial function, heart rhythm and conduction disorders, and adverse
      cardiovascular events. METHODS: Twenty-five CRC patients (12 women, mean age 61.3
      [35-76] years), all receiving six-month adjuvant CTX were included. Thirteen
      patients received 5-fluorouracil (5FU)-based CTX, and 12 patients received a
      capecitabine-based scheme. Subjects were assessed at baseline and followed-up
      three, six, and 12 months after the onset of treatment. In this analysis we
      focused on conduction abnormalities, systolic and diastolic function of the left
      ventricle (LV), and cardiovascular events. RESULTS: In 12-month follow-up a
      decrease of selected tissue Doppler parameters (e.g. S'IVS, S'lat, and E'sept)
      was observed, and it was significant. LV structural parameters and ejection
      fraction (EF) remained unaffected. Changes in myocardial performance were not
      influenced by CTX regimen or treatment with beta-blockers or angiotensin
      converting enzyme inhibitors. CTX did not affect LV structural parameters, EF, or
      conduction system, nor was it associated with cardiovascular events during the 12
      month follow-up. CONCLUSIONS: CTX in CRC patients does not affect LV structural
      parameters and EF. It may, however, trigger subtle changes in myocardial
      performance detectable by tissue Doppler echocardiography after 12 months.
      Moreover, it causes a transient increase of QT, which resolves after CTX
      cessation.

PMID- 27878804
TI  - Assessment of cardiovascular risk in patients undergoing total joint alloplasty:
      the CRASH-JOINT study.
AB  - BACKGROUND: Risk assessment is of particular importance for patients undergoing
      surgical interventions. Orthopaedic procedures, especially total joint
      alloplasty, are major procedures associated with high perioperative risk, as well
      as one of the highest rates of complications. AIM: The aim of the present study
      was to establish the prevalence of classical and non-classical cardiovascular
      risk factors in patients undergoing total hip or knee alloplasty. METHODS: The
      CRASH-JOINT (Cardiovascular Risk Assessment ScHeme in JOINT alloplasty) was a
      prospective, epidemiological study performed in consecutive patients scheduled
      for total joint (hip or knee) replacement surgery. Patients enrolled into the
      study were screened for cardiovascular risk factors and had ambulatory blood
      pressure performed for the diagnosis of hypertension. RESULTS: The present study
      enrolled 98 patients. During initial screening eight patients were disqualified
      from the study and the surgery, in the majority due to the cardiac causes. Sixty
      five patients had a hip joint replacement and 25 had knee joint replacement (mean
      age 63.7 +/- 12.2 years, 62.2% female). Fifty (55.6%) patients were diagnosed
      with arterial hypertension in the past, ten (11.1%) patients had diabetes
      mellitus, two (2.2%) had a history of myocardial infarction, and family history
      of cardiovascular disease was present in 24 (26.7%) cases. Mean body mass index
      (BMI) was 28.0 +/- 5.1 kg/m2 and 39 (43.3%) patients were overweight, while 28
      (31.1%) were obese. Patients undergoing hip replacement were significantly
      younger (61.8 +/- 12.6 vs. 68.5 +/- 10.0 years; p = 0.02), were more often
      current smokers (24.6% vs. 4.0%; p = 0.03), had significantly lower BMI (26.8 +/-
      4.5 vs. 31.2 +/- 5.3 kg/m2; p < 0.0001), and were less often obese (18.5% vs.
      64.0%; p < 0.0001). There were no significant differences between patients
      scheduled for primary surgery and reoperation. CONCLUSIONS: The study showed that
      classical cardiovascular risk factors in patients undergoing total hip or knee
      alloplasty have a higher prevalent than in the general population, which can
      potentially contribute to the higher risk of development of perioperative
      complications.

PMID- 27878805
TI  - Pancreatic enzyme replacement therapy for people with cystic fibrosis.
AB  - BACKGROUND: Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme
      replacement therapy to prevent malnutrition. Enzyme preparations need to be taken
      whenever food is taken, and the dose needs to be adjusted according to the food
      consumed. A systematic review on the efficacy and safety of pancreatic enzyme
      replacement therapy is needed to guide clinical practice, as there is variability
      between centres with respect to assessment of pancreatic function, time of
      commencing treatment, dose and choice of supplements. This is an updated version
      of a published review. OBJECTIVES: To evaluate the efficacy and safety of
      pancreatic enzyme replacement therapy in children and adults with cystic fibrosis
      and to compare the efficacy and safety of different formulations of this therapy
      and their appropriateness in different age groups. Also, to compare the effects
      of pancreatic enzyme replacement therapy in cystic fibrosis according to
      different diagnostic subgroups (e.g. different ages at introduction of therapy
      and different categories of pancreatic function). SEARCH METHODS: We searched the
      Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising
      references identified from comprehensive electronic database searches and
      handsearches of relevant journals and abstract books of conference proceedings.
      Most recent search: 15 July 2016.We also searched an ongoing trials website and
      the websites of the pharmaceutical companies who manufacture pancreatic enzyme
      replacements for any additional trials. Most recent search: 22 July 2016.
      SELECTION CRITERIA: Randomised and quasi-randomised controlled trials in people
      of any age, with cystic fibrosis and receiving pancreatic enzyme replacement
      therapy, at any dosage and in any formulation, for a period of not less than four
      weeks, compared to placebo or other pancreatic enzyme replacement therapy
      preparations. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      trials and extracted outcome data. They also assessed the risk of bias of the
      trials included in the review. MAIN RESULTS: One parallel trial and 12 cross-over
      trials of children and adults with cystic fibrosis were included in the review.
      The number of participants in each trial varied between 14 and 129 with a total
      of 512 participants included in the review. All the included trials were for a
      duration of four weeks. The included trials had mostly an unclear risk of bias
      from the randomisation process as the details of this were not given; they also
      mostly had a high risk of attrition bias and reporting bias.We could not combine
      data from all the trials as they compared different formulations. Findings from
      individual studies provided insufficient evidence to determine the size and
      precision of the effects of different formulations. Ten studies reported
      information on the review's primary outcome (nutritional status); however, we
      were only able to combine data from two small cross-over studies (n = 41). The
      estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval 
      0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically
      significant results favouring enteric-coated microspheres over enteric-coated
      tablets for our secondary outcomes stool frequency, mean difference -0.58 (95%
      confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with
      abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94;
      P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence
      interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over
      study also favoured enteric-coated microspheres over non-enteric-coated tablets
      with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95%
      confidence interval -0.90 to -0.50; P < 0.00001). AUTHORS' CONCLUSIONS: There is
      limited evidence of benefit from enteric-coated microspheres when compared to non
      enteric coated pancreatic enzyme preparations up to one month. In the only
      comparison where we could combine any data, the fact that these were cross-over
      studies is likely to underestimate the level of inconsistency between the results
      of the studies due to over-inflation of confidence intervals from the individual
      studies.There is no evidence on the long-term effectiveness and risks associated
      with pancreatic enzyme replacement therapy. There is also no evidence on the
      relative dosages of enzymes needed for people with different levels of severity
      of pancreatic insufficiency, optimum time to start treatment and variations based
      on differences in meals and meal sizes. There is a need for a properly designed
      study that can answer these questions.

PMID- 27878806
TI  - Larval and juvenile development of Tatia intermedia (Siluriformes:
      Auchenipteridae).
AB  - This study describes the morphology, morphometry and meristic characters of
      larval and juvenile Tatia intermedia collected in the middle Tocantins River and
      some of its tributaries. Six larvae of T. intermedia were examined and they have
      a moderately elongate body, head slightly dorso-ventrally depressed with a convex
      snout, small and round eyes and a subterminal mouth. In five juvenile stages
      observed, the head and eye are relatively smaller than in the larval stage and
      the snout remains convex and mouth becomes terminal.

PMID- 27878807
TI  - Manic switches induced by antidepressants: an umbrella review comparing
      randomized controlled trials and observational studies.
AB  - OBJECTIVE: We aimed to explore whether the prevalence of manic switch was
      underestimated in randomized controlled trials (RCTs) compared to observational
      studies (OSs). METHOD: Meta-analyses and simple and systematic reviews were
      identified by two reviewers in a blinded, standardized manner. All relevant
      references were extracted to include RCTs and OSs that provided data about manic
      switch prevalence after antidepressant treatment for a major depressive episode.
      The primary outcome was manic switch prevalence in the different arms of each
      study. A meta-regression was conducted to quantify the impact of certain
      variables on manic switch prevalence. RESULTS: A total of 57 papers (35 RCTs and
      22 OSs) were included in the main analysis. RCTs underestimated the rate of manic
      switch [0.53 (0.32-0.87)]. Overestimated prevalence was related to imipraminics
      [1.85 (1.22-2.79)]; to serotonin-norepinephrine reuptake inhibitors [1.74 (1.06
      2.86)]; and to other classes of drugs [1.58 (1.08-2.31)], compared to placebo
      treatment. The prevalence of manic switch was lower among adults than among
      children [0.2 (0.07-0.59)]; and higher [20.58 (8.41-50.31)] in case of bipolar
      disorder. CONCLUSION: Our results highlight an underestimation of the rates of
      manic switch under antidepressants in RCTs compared to the rates observed in
      observational studies.

PMID- 27878808
TI  - Interventions for tobacco use cessation in people in treatment for or recovery
      from substance use disorders.
AB  - BACKGROUND: Smoking rates in people with alcohol and other drug dependencies are
      two to four times those of the general population. Concurrent treatment of
      tobacco dependence has been limited due to concern that these interventions are
      not successful in this population or that recovery from other addictions could be
      compromised if tobacco cessation was combined with other drug dependency
      treatment. OBJECTIVES: To evaluate whether interventions for tobacco cessation
      are associated with tobacco abstinence for people in concurrent treatment for or
      in recovery from alcohol and other drug dependence. SEARCH METHODS: We searched
      the Cochrane Tobacco Addiction Group Specialised Register, the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, and clinicaltrials.gov
      databases, with the most recent search completed in August 2016. A grey
      literature search of conference abstracts from the Society on Nicotine Research
      and Treatment and the ProQuest database of digital dissertations yielded one
      additional study, which was excluded. SELECTION CRITERIA: We included randomised
      controlled trials assessing tobacco cessation interventions among people in
      concurrent treatment for alcohol or other drug dependence or in outpatient
      recovery programmes. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed study risk of bias and extracted data. We resolved
      disagreements by consensus. The primary outcome was abstinence from tobacco use
      at the longest period of follow-up, and the secondary outcome was abstinence from
      alcohol or other drugs, or both. We reported the strictest definition of
      abstinence. We summarised effects as risk ratios and 95% confidence intervals
      (CI). Two clustered studies did not provide intraclass correlation coefficients,
      and were excluded from the sensitivity analysis. We used the I2 statistic to
      assess heterogeneity. MAIN RESULTS: Thirty-five randomised controlled trials, one
      ongoing, involving 5796 participants met the criteria for inclusion in this
      review. Included studies assessed the efficacy of tobacco cessation
      interventions, including counselling, and pharmacotherapy consisting of nicotine
      replacement therapy (NRT) or non-NRT, or the two combined, in both inpatient and
      outpatient settings for participants in treatment and in recovery. Most studies
      did not report information to assess the risk of allocation, selection, and
      attrition bias, and were classified as unclear.Analyses considered the nature of
      the intervention, whether participants were in treatment or recovery and the type
      of dependency. Of the 34 studies included in the meta-analysis, 11 assessed
      counselling, 11 assessed pharmacotherapy, and 12 assessed counselling in
      combination with pharmacotherapy, compared to usual care or no intervention.
      Tobacco cessation interventions were significantly associated with tobacco
      abstinence for two types of interventions. Pharmacotherapy appeared to increase
      tobacco abstinence (RR 1.60, 95% CI 1.22 to 2.12, 11 studies, 1808 participants,
      low quality evidence), as did combined counselling and pharmacotherapy (RR 1.74,
      95% CI 1.39 to 2.18, 12 studies, 2229 participants, low quality evidence) at the
      period of longest follow-up, which ranged from six weeks to 18 months. There was
      moderate evidence of heterogeneity (I2 = 56% with pharmacotherapy and 43% with
      counselling plus pharmacotherapy). Counselling interventions did not
      significantly increase tobacco abstinence (RR 1.33, 95% CI 0.90 to
      1.95).Interventions were significantly associated with tobacco abstinence for
      both people in treatment (RR 1.99, 95% CI 1.59 to 2.50) and people in recovery
      (RR 1.33, 95% CI 1.06 to 1.67), and for people with alcohol dependence (RR 1.47,
      95% CI 1.20 to 1.81) and people with other drug dependencies (RR 1.85, 95% CI
      1.43 to 2.40).Offering tobacco cessation therapy to people in treatment or
      recovery for other drug dependence was not associated with a difference in
      abstinence rates from alcohol and other drugs (RR 0.97, 95% CI 0.91 to 1.03, 11
      studies, 2231 participants, moderate evidence of heterogeneity (I2 = 66%)).Data
      on adverse effect of the interventions were limited. AUTHORS' CONCLUSIONS: The
      studies included in this review suggest that providing tobacco cessation
      interventions targeted to smokers in treatment and recovery for alcohol and other
      drug dependencies increases tobacco abstinence. There was no evidence that
      providing interventions for tobacco cessation affected abstinence from alcohol
      and other drugs. The association between tobacco cessation interventions and
      tobacco abstinence was consistent for both pharmacotherapy and combined
      counselling and pharmacotherapy, for participants both in treatment and in
      recovery, and for people with alcohol dependency or other drug dependency. The
      evidence for the interventions was low quality due primarily to incomplete
      reporting of the risks of bias and clinical heterogeneity in the nature of
      treatment. Certain results were sensitive to the length of follow-up or the type
      of pharmacotherapy, suggesting that further research is warranted regarding
      whether tobacco cessation interventions are associated with tobacco abstinence
      for people in recovery, and the outcomes associated with NRT versus non-NRT or
      combined pharmacotherapy. Overall, the results suggest that tobacco cessation
      interventions incorporating pharmacotherapy should be incorporated into clinical
      practice to reduce tobacco addiction among people in treatment for or recovery
      from alcohol and other drug dependence.

PMID- 27878809
TI  - Telephone-assisted self-help for parents of children with attention
      deficit/hyperactivity disorder who have residual functional impairment despite
      methylphenidate treatment: a randomized controlled trial.
AB  - BACKGROUND: Self-help parenting interventions have been shown to be effective in
      the management of children with attention-deficit/hyperactivity disorder (ADHD)
      and may be useful when there are barriers to face-to-face therapist-led parent
      trainings. Previous studies indicate that behavioral interventions might be a
      useful adjunct to medication in children with residual ADHD symptoms, and
      regarding comorbid oppositional symptoms and multiple domains of functional
      impairment. In the present study, we examined whether a telephone-assisted self
      help (TASH) parenting behavioral intervention (written materials plus telephone
      counseling) enhanced the effects of methylphenidate treatment in children with
      ADHD. METHODS: In this randomized controlled trial, parents of 103 school-aged
      children with ADHD and residual functional impairment despite methylphenidate
      treatment were randomly assigned to either the enhancement group, which received
      the TASH intervention as adjunct to routine clinical care (including continued
      medication), or to the active control group, which received routine clinical care
      only (including continued medication). Parent-completed outcome measures at
      baseline and at 12 months (postassessment) included functional impairment, ADHD
      symptoms, oppositional defiant disorder (ODD) symptoms, parenting behavior, and
      parental satisfaction with the intervention (ClinicalTrials.gov: NCT01660425;
      URL: https://clinicaltrials.gov/ct2/show/NCT01660425). RESULTS: Intention-to
      treat analyses of covariance (ANCOVAs), which controlled for baseline data,
      revealed significant and moderate intervention effects for ODD symptoms and
      negative parenting behavior at the postassessment, whereas per-protocol analyses
      additionally showed significant and moderate effects on functional impairment
      (primary outcome). Parents expressed high satisfaction with the program.
      CONCLUSIONS: The TASH program enhances effects of methylphenidate treatment in
      families who complete the intervention. The discontinuation rate of about 30% and
      comparison between completing and discontinuing families suggest that the program
      may be more suitable for families with a higher educational level and fewer
      additional stresses.

PMID- 27878810
TI  - Improvement of phytoplankton culture isolation using single cell sorting by flow
      cytometry.
AB  - Flow cytometry provides a tool to physically sort single algal cells in order to
      obtain clonal cultures. During sorting, cells are submitted to physical stress
      factors such as high fluidic pressure, exposure to the laser beam, electrostatic
      charges, deflection through high voltage fields, and collisions with container
      surfaces. All of these can damage the cells of interest and success rates for
      initiation of cultures from flow-sorted cells are generally very low. We found
      that the addition of bovine serum albumin in the culture medium into which cells
      were sorted drastically improved the success of initiation of pico- and nano
      eukaryotic phytoplankton strains. Adding a mixture of antibiotics (Penicillin,
      Neomycin, Streptomycin) to the medium in order to slow down bacterial growth
      further improved culture development. This approach was successfully used to
      isolate taxonomically diverse strains, including novel taxa, from a fresh sample
      obtained in the English Channel and from enrichment cultures established during
      an Atlantic meridional transect cruise. We anticipate that these improvements
      will be useful to clone or purify existing cultures and to isolate novel cultures
      from oceanic samples.

PMID- 27878811
TI  - Adjuvant intraperitoneal chemotherapy for the treatment of gastric cancer at risk
      for peritoneal carcinomatosis: A systematic review.
AB  - The peritoneal surface is a frequent site of recurrence following surgery for
      gastric cancer. A systematic review and random effect analysis was undertaken to
      analyze current literature regarding the role of adjuvant intraperitoneal
      chemotherapy in gastric cancer. While pooled analysis supports the use of
      adjuvant IP chemotherapy in resectable gastric cancer, maximal benefit occured
      with intra-operative delivery, and possibly the use of MMC. J. Surg. Oncol.
      2017;115:192-201. (c) 2016 Wiley Periodicals, Inc.

PMID- 27878812
TI  - Perioperative blood transfusion: does it influence survival and cancer
      progression in metastatic spine tumor surgery?
AB  - BACKGROUND: Despite advances in surgical techniques for spinal metastases, there
      is often substantial blood loss, resulting in patients requiring blood
      transfusion during the perioperative period. Allogeneic blood transfusion (ABT)
      has been the main replenishment method for lost blood. However, the impact of ABT
      on cancer-related outcomes has been controversial in various studies. We aimed to
      evaluate the influence of perioperative ABT on disease progression and survival
      in patients undergoing metastatic spinal tumor surgery (MSTS). STUDY DESIGN AND
      METHODS: We conducted a retrospective study that included 247 patients who
      underwent MSTS at a single tertiary institution between 2005 and 2014. The impact
      of using perioperative ABT (either exposure to or quantities of transfusion) on
      disease progression and survival was assessed using Cox regression analyses while
      adjusting for potential confounding variables. RESULTS: Of 247 patients, 133
      (54%) received ABT. The overall median number of blood units transfused was 2
      (range, 0-10 units). Neither blood transfusion exposure nor quantities of
      transfusion were associated with overall survival (hazard ratio [HR], 1.15 [p =
      0.35] and 1.10 [p = 0.11], respectively) and progression-free survival (HR, 0.87
      [p = 0.18] and 0.98 [p = 0.11], respectively). The factors that influenced
      overall survival were primary tumor type and preoperative Eastern Cooperative
      Oncology Group performance status, whereas primary tumor type was the only factor
      that had an impact on progression-free survival. CONCLUSIONS: This is the first
      study providing evidence that disease progression and survival in patients who
      undergo MSTS are less likely to be influenced by perioperative ABT. The worst
      oncologic outcomes are more likely to be caused by the clinical circumstances
      necessitating blood transfusion, but not transfusion itself. However, because ABT
      can have a propensity toward developing postoperative infections, including
      surgical site infection, the use of patient blood management interventions would
      be worthwhile rather than relying solely on ABTs for these patients, if and
      whenever possible.

PMID- 27878813
TI  - No cases of perioperative allergy to local anaesthetics in the Danish Anaesthesia
      Allergy Centre.
AB  - BACKGROUND: Local anaesthetics (LA) are often suspected as possible causes of
      allergic reactions. The Danish Anaesthesia Allergy Centre (DAAC) is the national
      reference centre for investigation of perioperative allergic reactions. The
      purpose of this study was to investigate the incidence of IgE-mediated immediate
      type perioperative allergic reactions to LA. METHODS: In the period 2004-2013, a
      total of 409 patients (244 women/165 men; median age 49 years, range 1-86 years)
      were investigated in DAAC on suspicion of allergy associated with anaesthesia and
      surgery. A total of 162 (40%) patients were exposed to one or more LA. Suspected
      allergy to LA was investigated by prick test, intradermal test and subcutaneous
      provocation with the suspected drug. Patients with positive skin tests still
      underwent subcutaneous provocation, as false positive skin tests can occur.
      RESULTS: A total of 203 test series with LA were carried out on 162 patients (89
      women/73 men; mean age 49 years, range 2-85 years) with the following drugs:
      Lidocaine n = 80 (49%), bupivacaine n = 82 (51%), ropivacaine n = 31 (19%) and
      mepivacaine n = 10 (6%). All 162 patients had negative subcutaneous provocation
      for all tested LA (95% CI: 0-1.8%). Investigations revealed another allergen in
      52 of 162 patients. CONCLUSION: None of the 162 patients with suspected
      perioperative allergic reactions and exposure to LA reacted on subcutaneous
      provocation with the relevant LA. Thus, no patients have been diagnosed with
      allergy to LA in DAAC in the period 2004-2013 and allergy to LA must be
      considered very rare in this population.

PMID- 27878814
TI  - Giant kelp vegetative propagation: Adventitious holdfast elements rejuvenate
      senescent individuals of the Macrocystis pyrifera "integrifolia" ecomorph.
AB  - Recent findings on holdfast development in the giant kelp highlighted its key
      importance for Macrocystis vegetative propagation. We report here for the first
      time the development of adventitious holdfasts from Macrocystis stipes. Swellings
      emerge spontaneously from different areas of the stipes, especially in senescent
      or creeping individuals. After being manually fastened to solid substrata, these
      swellings elongated into haptera, which became strongly attached after 1 month.
      Within 4 months, new thalli increased in size and vitality, and developed
      reproductive fronds. Our results suggest the usage of these structures for
      auxiliary attachment techniques. These could act as a backup, when primary
      holdfasts are weak, and thus improve the survival rate of the giant kelp in
      natural beds.

PMID- 27878815
TI  - Interventions to reduce cognitive impairments following critical illness: a
      topical systematic review.
AB  - BACKGROUND: Critical illness is associated with cognitive impairments. Effective
      treatment or prevention has not been established. The aim of this review was to
      create a systematic summary of the current evidence concerning clinical
      interventions during intensive care admission to reduce cognitive impairments
      after discharge. METHODS: Medline, Embase, Cochrane Central, PsycInfo and Cinahl
      were searched. Inclusion criteria were studies assessing the effect of
      interventions during intensive care admission on cognitive function in adult
      patients. Studies were excluded if they were reviews or reported solely on
      survivors of cardiac arrest, stroke or traumatic brain injury. RESULTS: Of 4877
      records were identified. Seven studies fulfilled the eligibility criteria. The
      interventions described covered strategies for enteral nutrition, fluids,
      sedation, weaning, mobilization, cognitive activities, statins and sleep quality
      improvement. Data were synthesized to provide an overview of interventions,
      quality, follow-up assessments and neuropsychological outcomes. CONCLUSION: None
      of the interventions had significant positive effects on cognitive impairments
      following critical illness. Quality was negatively affected by study limitations,
      imprecision and indirectness in evidence. Clinical research on cognition is
      feasible, but large, well designed trials with a specific aim at reducing
      cognitive impairments are needed.

PMID- 27878816
TI  - Diel shifts in the structure and function of nearshore estuarine fish
      communities.
AB  - Day-night shifts in the nearshore fish fauna of a temperate microtidal estuary
      were assessed using a holistic suite of structural and functional community
      attributes. Mean fish species richness and diversity (taxonomic distinctness)
      were higher at night across all regions of the estuary and seasons, concurring
      with the findings of numerous comparable studies reviewed worldwide, while the
      diel period in which mean abundance was higher varied among seasons. Likewise,
      species and functional guild compositions (the latter based on feeding modes and
      habitat use) both differed significantly between day and night, with the extent
      of the diel shift again varying seasonally. Daytime fish communities were
      characterized by higher abundances of Atherinidae, Sillaginidae and Mugilidae,
      while Gobiidae were far more abundant at night. Marked shifts in size composition
      were also evident, with smaller fishes (<100 mm total length, LT ) being more
      prevalent during the day and larger fishes (>=200 mm LT ) proportionally more
      abundant at night. The above diel shifts were feasibly related to a range of
      predator-prey interactions and feeding-related movements, namely a nocturnal
      decrease in top-order avian piscivory coupled with an increase in invertebrate
      prey availability, resulting in changes in the presence and catchability of
      certain fish species in shallow estuarine waters.

PMID- 27878817
TI  - Structural characterization of CYP260A1 from Sorangium cellulosum to investigate
      the 1alpha-hydroxylation of a mineralocorticoid.
AB  - In this study, we report the crystal structure of the cytochrome P450 CYP260A1
      (PDB 5LIV) from the myxobacterium Sorangium cellulosum So ce56. In addition, we
      investigated the hydroxylation of 11-deoxycorticosterone by CYP260A1 by
      reconstituting the enzyme with the surrogate redox partners adrenodoxin and
      adrenodoxin reductase. The major product of this steroid conversion was
      identified as 1alpha-hydroxy-11-deoxycorticosterone, a novel Delta4 C-21
      steroidal derivative. Furthermore, we docked the substrate into the crystal
      structure and replaced Ser326, the residue responsible for substrate orientation,
      with asparagine and observed that the mutant S326N displayed higher activity and
      selectivity for the formation of 1alpha-hydroxy-11-deoxycorticosterone compared
      to the wild-type CYP260A1. Thus, our findings highlight the usefulness of the
      obtained crystal structure of CYP260A1 in identifying biotechnologically more
      efficient reactions.

PMID- 27878818
TI  - Virtual reconstruction of the skeletal labyrinth of two lamnid sharks
      (Elasmobranchii, Lamniformes).
AB  - The first virtual reconstruction of the skeletal labyrinth of the porbeagle shark
      Lamna nasus and the shortfin mako shark Isurus oxyrinchus is presented here using
      high-resolution micro-computed tomography. The results, in comparison with
      previously published information, suggest relationships between skeletal
      labyrinth morphology and locomotion mode in chondrichthyans, but also show that
      further studies are required to establish such connections. Nevertheless, this
      study adds to the knowledge of the skeletal labyrinth morphology in two apex
      elasmobranch species.

PMID- 27878819
TI  - Vitiligo and depression: a systematic review and meta-analysis of observational
      studies.
AB  - Vitiligo is a common depigmenting disorder with profound psychosocial impacts.
      Previous observational studies have suggested a link between vitiligo and
      psychiatric morbidity, such as depression. However, variability in study design
      makes it difficult to quantify accurately the relationship between vitiligo and
      depression. We aimed to investigate the underlying prevalence and risk of
      depression among patients with vitiligo. A comprehensive search of MEDLINE,
      Embase and the Cochrane Library was conducted. Cross-sectional, case-control or
      cohort studies that assessed the prevalence of depression among patients with
      vitiligo or the relationship between vitiligo and depression were included.
      DerSimonian and Laird random-effects models were utilized to calculate the pooled
      prevalence and relative risks. Publication bias was evaluated by funnel plots and
      Egger's tests. Twenty-five studies with 2708 cases of vitiligo were included.
      Based on diagnostic codes, the pooled prevalence of depression among patients
      with vitiligo was 0.253 [95% confidence interval (CI) 0.16-0.34; P < 0.001)].
      Using self-reported questionnaires, the pooled prevalence of depressive symptoms
      was 0.336 (95% CI 0.25-0.42; P < 0.001). The pooled odds ratio of depression
      among patients with vitiligo was 5.05 vs. controls (95% CI 2.21-11.51; P <
      0.001). Moderate-to-high heterogeneity was observed between the studies. Patients
      with vitiligo were significantly more likely to suffer from depression. Clinical
      depression or depressive symptoms can be prevalent, with the actual prevalence
      differing depending on screening instruments or, possibly, geographical regions.
      Clinicians should actively evaluate patients with vitiligo for signs/symptoms of
      depression and provide appropriate referrals to manage their psychiatric symptoms
      accordingly.

PMID- 27878820
TI  - Youth and the Great Recession: Are values, achievement orientation and outlook to
      the future affected?
AB  - This special section brings together leading experts in psychology and sociology
      to examine the consequences of the Great Recession for young people's values,
      achievement orientation, and outlook to the future. Evidence from Europe and the
      United States suggests that the impact of the recession varies for distinct
      outcomes and by age, the latter pointing to potential sensitive periods for
      interventions. Although the direct effects of the recession are not strong, they
      accelerate pre-existing trends towards more prolonged and precarious transitions
      to independence, and are likely to bring with them long-term scarring with
      respect to health and well-being. While feelings of self-confidence and self
      worth have eroded, young people continue to subscribe to the "American Dream,"
      the belief that in principle it is possible to make it - even if limitations to
      one's own capabilities are recognised. Trust in institutions has declined, but
      support and concern for others have increased, suggesting that in times of
      economic hardship and uncertainty social relationships become more salient. Young
      people's response to the recession appears to be less of a "me-first" reaction
      than "let's help each other": a form of "collective agency" to counter the
      inadequacy of social safety nets.

PMID- 27878821
TI  - Liver transplantation for fibrolamellar hepatocellular carcinoma: A national
      perspective.
AB  - BACKGROUND: Fibrolamellar Hepatocellular Carcinoma (FL-HCC) is a rare primary
      liver tumor that usually presents in younger patients without underlying liver
      disease. METHODS: We queried the United Network of Organ Sharing (UNOS) database
      between October 1988 and January 2013 to evaluate outcomes in patients with FL
      HCC undergoing liver transplantation in the United States compared to patients
      with conventional Hepatocellular Carcinoma (HCC). RESULTS: Sixty-three patients
      were identified (57% female, mean age 30 years). Only one patient (2%) had an
      associated Hepatitis C Virus. Mean Model for End-Stage Liver Disease (MELD) score
      at the time of transplantation was 11.3. Mean waiting time was 325 days and mean
      cold ischemic time was 6 hr. Overall survival of FL-HCC patients at 1, 3, and 5
      years was 96%, 80%, and 48% as compared to HCC patients whose rates were 89%,
      77%, and 68%. Six patients had tumor recurrence (10%). The Cox Model demonstrated
      that MELD and cold ischemic time are the strongest predictors of overall survival
      in FL-HCC patients. Age and wait time were not associated with poor patient
      survival in this series. CONCLUSIONS: Good results can be obtained in selected
      patients transplanted for FL-HCC. FL-HCC patients had similar survival compared
      to those transplanted for HCC. J. Surg. Oncol. 2017;115:319-323. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27878823
TI  - Owning the tooth: exploring the ethical and legal issues relating to the use of
      extracted human teeth in dental education in Australia.
AB  - Extracted human teeth have been used to practice operative techniques for a very
      long time. As a natural surrogate for a live tooth in vivo, their use has
      traditionally been very important for the development of skills in trainee
      dentists, as well as their qualified colleagues who wish to practise existing or
      new skills. As synthetic alternatives develop greater authenticity, alongside a
      society in which many retain their natural dentition well into old age, the
      current paradigm relating to how extracted teeth in dental education are used
      needs to be revisited. An ethical and legal dilemma that must be addressed within
      dental education relates to where and how teeth may be sourced. This article will
      seek to question whether there is a legal or ethical requirement to gain consent
      for the use of extracted teeth from patients, as well as exploring the status of
      whether extracted dental tissue can be considered to be the property of either
      patient or surgeon. Whilst synthetic alternatives are being utilized more
      frequently in education, it is unlikely that they will completely replace
      extracted natural teeth in the immediate future. It is therefore imperative that
      their use complies with legal doctrine and contemporary ethical thought.

PMID- 27878824
TI  - Minimal intervention dentistry for early childhood caries and child dental
      anxiety: a randomized controlled trial.
AB  - BACKGROUND: To compare changes in child dental anxiety after treatment for early
      childhood caries (ECC) using two treatment approaches. METHODS: Children with ECC
      were randomized to test (atraumatic restorative treatment (ART)-based approach)
      or control (standard care approach) groups. Children aged 3 years or older
      completed a dental anxiety scale at baseline and follow up. Changes in child
      dental anxiety from baseline to follow up were tested using the chi-squared
      statistic, Wilcoxon rank sum test, McNemar's test and multinomial logistic
      regression. RESULTS: Two hundred and fifty-four children were randomized (N = 127
      test, N = 127 control). At baseline, 193 children completed the dental anxiety
      scale, 211 at follow up and 170 completed the scale on both occasions. Children
      who were anxious at baseline (11%) were no longer anxious at follow up, and 11%
      non-anxious children became anxious. Multinomial logistic regression found each
      increment in the number of visits increased the odds of worsening dental anxiety
      (odds ratio (OR), 2.2; P < 0.05), whereas each increment in the number of
      treatments lowered the odds of worsening anxiety (OR, 0.50; P = 0.05).
      CONCLUSIONS: The ART-based approach to managing ECC resulted in similar levels of
      dental anxiety to the standard treatment approach and provides a valuable
      alternative approach to the management of ECC in a primary dental care setting.

PMID- 27878822
TI  - Wide variations in blood product transfusion practices among providers who care
      for patients with acute leukemia in the United States.
AB  - BACKGROUND: Transfusion of blood products is a key component of the supportive
      management in patients with acute leukemia (AL). However high-quality trial
      evidence and clinical outcome data to support specific transfusion goals for
      blood products for patients with AL remain limited leading to diverse transfusion
      practices. The primary objective of this study was to determine the spectrum of
      transfusion patterns in a variety of care settings among providers who treat AL
      patients. STUDY DESIGN AND METHODS: A 31-question survey queried providers caring
      for AL patients about the existence of institutional guidelines for transfusion
      of blood products, transfusion triggers for hemoglobin (Hb), platelets (PLTs),
      and fibrinogen in various settings including inpatient and outpatient and before
      procedures. RESULTS: We analyzed 130 responses and identified divergent
      transfusion Hb goals in hospitalized and ambulatory patients, fibrinogen goals
      for cryoprecipitate transfusions, and variation in practice for use of certain
      PLTs and red blood cell products. The least variable transfusion patterns were
      reported for PLT goals in thrombocytopenia and in the setting of invasive
      procedures such as bone marrow biopsy and lumbar punctures. CONCLUSIONS: This
      survey confirmed wide variations in blood product transfusion practices across
      several clinical scenarios in patients with AL. The findings emphasized the need
      for large prospective randomized trials to develop standardized evidence-based
      guidelines for blood product transfusions in patients with AL with the goal of
      limiting unnecessary transfusions without compromising outcomes.

PMID- 27878826
TI  - A multifaceted risk analysis of fathers' self-reported physical violence toward
      their children.
AB  - Existing research has shown that child maltreatment is carried out by both
      mothers and fathers. There is also an extensive body of literature analyzing
      reasons for mothers' violent behavior. Among fathers, reasons are less well
      studied, resulting in the lack of a comprehensive picture of paternal child
      abuse. In this study, 20 child-, parent-, and family-related factors have been
      included in a combined analysis to assess which of these may pose a risk for
      fathers' severe violent behavior toward their children. The study is based on
      merged data from Finland and Sweden, in which an anonymous survey was answered by
      parents, based on representative samples of parents with 0-12-year-old children.
      The merged data set included 679 fathers and analyses were carried out using
      logistic regression models. Six percent of the fathers had committed severe
      violent acts, that is, slapped, hit, punched, kicked, bit, hit/tried to hit their
      child with an object or shook (under 2-year-old) their child at least once during
      the 12 months preceding the survey. Corporal punishment experienced by the
      fathers when they were children, or used by the father as a method of discipline,
      strongly increased the likelihood of severe violent acts. The findings emphasize
      the importance of preventing all forms of corporal punishment in seeking to
      minimize the occurrence of severe physical violence by fathers toward their
      children. Aggr. Behav. 43:317-328, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27878825
TI  - Mismatch of morphological and molecular identifications in native and invasive
      subspecies of Codium fragile (Bryopsidophyceae, Chlorophyta).
AB  - Several subspecies are defined within Codium fragile, including the invasive C.
      fragile ssp. fragile, first reported in New Zealand in 1973. An endemic
      subspecies, C. fragile ssp. novae-zelandiae, is also found throughout New
      Zealand. The two subspecies exhibit morphological and molecular variation,
      although these have never been evaluated together. We compared variation between
      subspecies at locations in Auckland, identifying subspecies using rps3-rpl16 DNA
      sequence data, and assessing gross morphological differences, anatomical utricle
      characters and morphometrics. The taxonomic utility of the morphometric data sets
      was assessed by linear discriminant analysis. Utricle characters and measurements
      varied within individual thalli and between different preservation methods. The
      phenotypes of both subspecies were highly variable and influenced by environment.
      Accurate subspecies delimitation using morphological data was not possible; the
      discriminant analyses performed no better than chance for all combinations of the
      morphological data. Specimens from New Zealand, Canada, Australia and Ireland
      were sequenced using both the rps3-rpl16 and tufA plastid markers. The tufA
      elongation factor was shown to be a good candidate for differentiating subspecies
      of C. fragile. This marker is twice the length of the rps3-rpl16 spacer, shows
      greater variation between ssp. fragile and novae-zelandiae, and is less prone to
      sequencing error. A simple restriction enzyme digest of the tufA amplicon can
      distinguish ssp. fragile and ssp. novae-zelandiae. Our study expands the known
      range of the ssp. fragile in New Zealand, including the first record of this
      subspecies from the west coast of Auckland, and points to a need to re-evaluate
      morphological and molecular criteria for subspecies currently defined within C.
      fragile.

PMID- 27878827
TI  - Review article: mesenchymal stromal cell therapy for inflammatory bowel diseases.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are chronic relapsing diseases in
      which pro-inflammatory immune cells and cytokines induce intestinal tissue damage
      and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory
      effects and stimulate tissue repair. AIM: To review the current data on
      mesenchymal stromal cell therapy in IBD. METHOD: We searched PubMed and
      'ClinicalTrials.gov' databases using the terms 'mesenchymal stromal cells',
      'mesenchymal stem cell transplantation', 'inflammatory bowel diseases', 'Crohn
      disease' and 'colitis, ulcerative'. Additional publications were identified from
      individual article reference lists. RESULTS: MSCs include inhibition of Th1/Th17
      lymphocytes and recruitment of regulatory T lymphocytes, induction of antigen
      presenting cells into a regulatory-like profile, and stimulation of epithelial
      cell differentiation and proliferation. More than 200 patients with refractory
      fistulas have been treated with local injections of MSCs, resulting in complete
      response in more than half, and in overall response in approximately two thirds
      of patients. In refractory luminal Crohn's disease, 49 cases of systemic MSC
      infusions have been reported, while trials with autologous MSCs resulted in
      mitigated responses, studies using allogeneic MSCs were promising, with around
      60% of patients experiencing a response and around 40% achieving clinical
      remission. CONCLUSIONS: Mesenchymal stromal cells might represent a promising
      therapy for IBD, especially for Crohn's disease. There remain many unsolved
      questions concerning the optimal origin and source of mesenchymal stromal cells,
      dosage and modalities of administration. Moreover, mesenchymal stromal cells
      still need to prove their effectiveness compared with conventional treatments in
      randomised controlled trials.

PMID- 27878828
TI  - RHS6 coordinately regulates the Th2 cytokine genes by recruiting GATA3, SATB1,
      and IRF4.
AB  - BACKGROUND: Asthma is a Th2 cell-driven inflammatory disease and a major public
      health concern. The cis-acting element Rad50 hypersensitive site 6 (RHS6) in the
      Th2 locus control region is essential for regulation of the Th2 cytokine genes;
      however, its role in allergic airway inflammation and underlying molecular
      mechanisms of the regulation by RHS6 are poorly understood. OBJECTIVE: We sought
      to understand the role of RHS6 in the development of allergic airway inflammation
      and its molecular mechanism for Th2 cytokine expression. METHODS: We used an
      ovalbumin-induced allergic inflammation model with RHS6-deficient mice to examine
      the role of RHS6 in this process. To examine molecular mechanism of RHS6 for Th2
      cytokine expression, we used DNA affinity chromatography and mass spectrometry,
      quantitative RT-PCR, ELISA, intracellular cytokine staining, chromatin
      immunoprecipitation, and co-immunoprecipitation. RESULTS: Deletion of RHS6 caused
      a dramatic resistance to allergic airway inflammation. RHS6 recruited
      transcription factors GATA3, SATB1, and IRF4, which play important roles in
      expression of all three Th2 cytokine genes. RHS6 deficiency caused inhibition of
      transcription factor-induced Th2 cytokine gene expression. CONCLUSION: RHS6 is a
      critical regulatory element for allergic airway inflammation and for coordinate
      regulation of Th2 cytokine genes by recruiting GATA3, SATB1, and IRF4.

PMID- 27878829
TI  - Genetic association of PLAG1, SCD, CYP7B1 and FASN SNPs and their effects on
      carcass weight, intramuscular fat and fatty acid composition in Hanwoo steers
      (Korean cattle).

PMID- 27878830
TI  - Clinical Assessment of Histidine-Tryptophan-Ketoglutarate Solution and Modified
      St. Thomas' Solution in Pediatric Cardiac Surgery of Tetralogy of Fallot.
AB  - The objective of this study is to compare the myocardium protective effect of
      Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution versus Modified
      St. Thomas' (STH) solution in pediatric cardiac surgery of Tetralogy of Fallot
      (TOF). Seventy-seven pediatric patients of TOF who received the total surgical
      repair were reviewed, from January 2014 to October 2015. A horizontal comparison
      between HTK solution and modified STH solution has been made since the HTK
      solutions were started to be used in our hospital. The patients were divided into
      the HTK group (n = 35) and the STH group (n = 33). The perioperative values of
      the groups were assessed in this study. The primary endpoints including
      spontaneous cardiac re-beating time, intensive care unit (ICU) stay, overall
      stay, mechanical ventilation postoperation, postoperation stay, overall stay, and
      perioperative echocardiographic results were analyzed in this study. We found
      that spontaneous cardiac re-beating time of the HTK group was significantly
      shorter than that of the STH group (0.26 min +/- 0.56 vs. 1.33 +/- 1.02, P <
      0.001). There were no significant differences between the two groups in ICU stay
      (P = 0.29), postoperative mechanical ventilation time (P = 0.84), overall stay
      (0.73); and the mortalities of the two groups were similar (2.9 vs. 3.0%). Aimed
      at pediatric cardiac surgery of TOF, this study suggests that with similar aorta
      cross-clamping time, modified STH solution is as safe as HTK solution.

PMID- 27878831
TI  - IkappaBNS induces Muc5ac expression in epithelial cells and causes airway hyper
      responsiveness in murine asthma models.
AB  - BACKGROUND: In allergic asthma, environmental allergens including house dust mite
      (HDM) trigger pattern recognition receptors and activate downstream signaling
      pathways including NF-kappaB pathways not only in immune cells but also in airway
      epithelial cells. Recent studies have shown that NF-kappaB activation is
      regulated positively or negatively depending on the cellular context by IkappaBNS
      (encoded by the gene Nfkbid), one of atypical IkappaB proteins, in the nucleus.
      Therefore, we hypothesized that IkappaBNS expressed in immune cells or epithelial
      cells is involved in the regulation of asthmatic responses. AIM: To determine the
      roles of IkappaBNS in HDM-induced asthmatic responses. METHODS: Roles of
      IkappaBNS in HDM-induced airway inflammation and airway hyper-responsiveness
      (AHR) were examined by using IkappaBNS-deficient (Nfkbid-/- ) mice. Roles of
      IkappaBNS expressed in hematopoietic cells and nonhematopoietic cells were
      separately evaluated by bone marrow chimeric mice. Roles of IkappaBNS expressed
      in murine tracheal epithelial cells (mTECs) were examined by air-liquid interface
      culture. RESULTS: House dust mite-induced airway inflammation and AHR were
      exacerbated in mice lacking IkappaBNS in hematopoietic cells. In contrast, HDM
      induced airway inflammation was exacerbated, but AHR was attenuated in mice
      lacking IkappaBNS in nonhematopoietic cells. The induction of Muc5ac, a
      representative mucin in asthmatic airways, was reduced in Nfkbid-/- mTEC, whereas
      the induction of Spdef, a master regulator of goblet cell metaplasia, was not
      impaired in Nfkbid-/- mTEC. Moreover, IkappaBNS bound to and activated the MUC5AC
      distal promoter in epithelial cells. CONCLUSION: IkappaBNS is involved in
      inducing Muc5ac expression in lung epithelial cells and causing AHR in HDM
      induced asthma models.

PMID- 27878832
TI  - Prenatal cfDNA screening results indicative of maternal neoplasm: survey of
      current practice and management needs.
AB  - OBJECTIVE: To determine genetic counselors' current practices and management
      needs for patients with prenatal cfDNA screening results indicative of maternal
      neoplasm. METHODS: A survey was completed by genetic counselors recruited via the
      National Society of Genetic Counselors (NSGC). RESULTS: Over 300 genetic
      counselors were surveyed. Almost all participants (95%) were aware that
      Noninvasive Prenatal Testing (NIPT) results may suggest maternal neoplasm, and
      77% reported they would disclose such results. However, only 29% routinely
      communicate this possibility to patients in a pre-test setting. Management
      recommendations made by counselors were highly variable, and over half (51.8%)
      stated they would feel uncomfortable or very uncomfortable counseling a patient
      with these results. While less than half (44.3%) believed the current benefits of
      NIPT's ability to suggest maternal neoplasm outweigh its potential harms, 80.2%
      recognized it would be beneficial in the future. A vast majority of counselors
      (91.3%) felt institutional or national guidelines were needed for patient
      management. CONCLUSION: A majority of counselors neither felt properly equipped
      nor comfortable counseling patients with prenatal cfDNA results suggestive of
      maternal neoplasm. This study demonstrates a need for collaboration amongst
      clinicians, researchers, and laboratories to publish data regarding NIPT results
      indicative of maternal neoplasm, and for the creation of management guidelines.
      (c) 2016 John Wiley & Sons, Ltd.

PMID- 27878833
TI  - Presence of intraepithelial food antigen in patients with active eosinophilic
      oesophagitis.
AB  - BACKGROUND: Although eosinophilic oesophagitis (EoE) is putatively mediated by an
      abnormal response to food antigen, the oesophagus is considered relatively
      impermeable to large molecules. AIM: To assess whether food antigens penetrate
      the oesophageal mucosa in patients with EoE. METHODS: Anti-gliadin staining was
      performed in three groups: active EoE, inactive EoE and EoE patients on a low or
      gluten free diet. To appraise the specificity of our results, we also performed
      gliadin staining on six patients without oesophageal disease who were consuming
      gluten. The groups with EoE on gluten also underwent endoscopic infusion with
      gluten containing soy sauce and repeat biopsies during the endoscopy. We measured
      eosinophil density, dilated intercellular spaces (on a 0-4+ scale) and gliadin in
      oesophageal mucosa by immunofluorescence. RESULTS: Patients with active EoE had
      significantly greater epithelial density of anti-gliadin staining when compared
      to inactive EoE (P < 0.0065) and gluten-free patients (P < 0.0008) at baseline
      and after soy infusion. Gliadin was not detected in non-EoE control patients. The
      distribution of gliadin was both cytoplasmic and nuclear. There was good
      correlation of dilated intercellular spaces grade and total gliadin staining
      intensity (r = 0.577, P = 0.0077). Acute oesophageal perfusion of a commercial
      gliadin-rich soy sauce did not lead to an increase in gliadin staining in active
      or inactive EoE. CONCLUSION: These findings suggest, although do not prove, that
      antigen penetration in active eosinophilic oesophagitis might be facilitated by
      impairment of epithelial integrity.

PMID- 27878834
TI  - Characterization of miRNAs involved in response to poly(I:C) in porcine airway
      epithelial cells.
AB  - MicroRNAs (miRNA) have been implicated in a variety of pathological conditions
      including infectious diseases. Knowledge of the miRNAs affected by poly(I:C), a
      synthetic analog of viral double-stranded RNA, in porcine airway epithelial cells
      (PAECs) contributes to understanding the mechanisms of swine viral respiratory
      diseases, which bring enormous economic loss worldwide every year. In this study,
      we used high throughput sequencing to profile miRNA expression in PAECs treated
      with poly(I:C) as compared to the untreated control. This approach revealed 23
      differentially expressed miRNAs (DEMs), five of which have not been implicated in
      viral infection before. Nineteen of the 23 miRNAs were down-regulated including
      members of the miR-17-92 cluster, a well-known polycistronic oncomir and
      extensively involved in viral infection in humans. Target genes of DEMs,
      predicted using bioinformatic methods and validated by luciferase reporter
      analysis on two representative DEMs, were significantly enriched in several
      pathways including transforming growth factor-beta signaling. A large quantity of
      sequence variations (isomiRs) were found including a substitution at position 5,
      which was verified to redirect miRNAs to a new spectrum of targets by luciferase
      reporter assay together with bioinformatics analysis. Twelve novel porcine miRNAs
      conserved in other species were identified by homology analysis together with
      cloning verification. Furthermore, the expression analysis revealed the potential
      importance of three novel miRNAs in porcine immune response to viruses. Overall,
      our data contribute to clarifying the mechanisms underlying the host immune
      response against respiratory viruses in pigs, and enriches the repertoire of
      porcine miRNAs.

PMID- 27878835
TI  - First-line therapy for chronic lymphocytic leukemia in patients older than 79
      years is feasible and achieves good results: A FILO retrospective study.
AB  - The mean age at diagnosis of chronic lymphocytic leukemia (CLL) is 72 years, with
      22.8% of patients being older than 80 years. However, the elderly are
      underrepresented in clinical studies of CLL. We performed a retrospective study
      of CLL patients aged 80 years or older at the initiation of first-line therapy in
      hospitals affiliated with the French intergroup on CLL (French Innovative
      Leukemia Organization) between 2003 and 2013. Here, we describe the clinical and
      biological characteristics, treatment, and outcomes for 201 patients. The median
      age of the cohort was 83.2 years (80-92 years). The median Cumulative Index
      Rating Scale comorbidity score was 5 and the median creatinine clearance was 48
      mL/min (Cockcroft-Gault formula). At treatment initiation, Binet stage was A
      (26.4%), B (27.9%), or C (40.3%). Therapy consisted mainly of chlorambucil
      (65.7%), bendamustine (10.5%), and rituximab (44.3%) as follows: chlorambucil
      alone (45.3%) or immunochemotherapy (48.3%) with rituximab + chlorambucil
      (22.7%), rituximab + bendamustine (10.4%), or rituximab + cyclophosphamide +
      dexamethasone (5.5%). The overall response rate was 66.2% with 31.8% clinical
      complete remission. The median overall and progression-free survival from
      treatment initiation was 53.7 and 18.3 months, respectively. These results
      suggest that treatment is feasible in this age group, even with
      immunochemotherapy. Thus, prospective trials should target this population and
      oncogeriatric evaluation and new targeted therapies should be part of such future
      trials.

PMID- 27878836
TI  - Social comparison, personal relative deprivation, and materialism.
AB  - Across five studies, we found consistent evidence for the idea that personal
      relative deprivation (PRD), which refers to resentment stemming from the belief
      that one is deprived of deserved outcomes compared to others, uniquely
      contributes to materialism. In Study 1, self-reports of PRD positively predicted
      materialistic values over and above socioeconomic status, personal power, self
      esteem, and emotional uncertainty. The experience of PRD starts with social
      comparison, and Studies 2 and 3 found that PRD mediated the positive relation
      between a tendency to make social comparisons of abilities and materialism. In
      Study 4, participants who learned that they had less (vs. similar) discretionary
      income than people like them reported a stronger desire for more money relative
      to donating more to charity. In Study 5, during a windfall-spending task,
      participants higher in PRD spent more on things they wanted relative to other
      spending categories (e.g., paying off debts).

PMID- 27878837
TI  - Thrombotic Depositions on Right Impeller of Double-Ended Centrifugal Total
      Artificial Heart In Vivo.
AB  - The development of total artificial heart devices is a complex undertaking that
      includes chronic biocompatibility assessment of the device. It is considered
      particularly important to assess whether device design and features can be
      compatible long term in a biological environment. As part of the development
      program for the Cleveland Clinic continuous-flow total artificial heart (CFTAH),
      we evaluated the device for signs of thrombosis and biological material
      deposition in four animals that had achieved the intended 14-, 30-, or 90-day
      durations in each respective experiment. Explanted CFTAHs were analyzed for
      possible clot buildup at "susceptible" areas inside the pump, particularly the
      right pump impeller. Depositions of various consistency and shapes were observed.
      We here report our findings, along with macroscopic and microscopic analysis post
      explant, and provide computational fluid dynamics data with its potential
      implications for thrombus formation.

PMID- 27878838
TI  - Cluster detection of spatial regression coefficients.
AB  - Popular approaches to spatial cluster detection, such as the spatial scan
      statistic, are defined in terms of the responses. Here, we consider a varying
      coefficient regression and spatial clusters in the regression coefficients. For
      varying-coefficient regression, such as the geographically weighted regression,
      different regression coefficients are obtained for different spatial units. It is
      often of interest to the practitioners to identify clusters of spatial units with
      distinct patterns in a regression coefficient, but there is no formal statistical
      methodology for that. Rather, cluster identification is often ad-hoc such as by
      eyeballing the map of fitted regression coefficients and discerning patterns. In
      this paper, we develop new methodology for spatial cluster detection in the
      regression setting based on hypotheses testing. We evaluate our methods in terms
      of power and coverages for true clusters via simulation studies. For
      illustration, our methodology is applied to a cancer mortality dataset. Copyright
      (c) 2016 John Wiley & Sons, Ltd.

PMID- 27878839
TI  - A U-statistics based approach to sample size planning of two-arm trials with
      discrete outcome criterion aiming to establish either superiority or
      noninferiority.
AB  - In current practice, the most frequently applied approach to the handling of ties
      in the Mann-Whitney-Wilcoxon (MWW) test is based on the conditional distribution
      of the sum of mid-ranks, given the observed pattern of ties. Starting from this
      conditional version of the testing procedure, a sample size formula was derived
      and investigated by Zhao et al. (Stat Med 2008). In contrast, the approach we
      pursue here is a nonconditional one exploiting explicit representations for the
      variances of and the covariance between the two U-statistics estimators involved
      in the Mann-Whitney form of the test statistic. The accuracy of both ways of
      approximating the sample sizes required for attaining a prespecified level of
      power in the MWW test for superiority with arbitrarily tied data is comparatively
      evaluated by means of simulation. The key qualitative conclusions to be drawn
      from these numerical comparisons are as follows: With the sample sizes calculated
      by means of the respective formula, both versions of the test maintain the level
      and the prespecified power with about the same degree of accuracy. Despite the
      equivalence in terms of accuracy, the sample size estimates obtained by means of
      the new formula are in many cases markedly lower than that calculated for the
      conditional test. Perhaps, a still more important advantage of the nonconditional
      approach based on U-statistics is that it can be also adopted for noninferiority
      trials. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27878840
TI  - Challenging behaviours in adults with an intellectual disability: A total
      population study and exploration of risk indices.
AB  - OBJECTIVES: Considerable variation has been reported in the prevalence and
      correlates of challenging behaviour (CB) in adults with intellectual disabilities
      (ID). To provide a robust estimate of prevalence, we identified the entire
      administrative population of adults with ID in a defined geographical area and
      used a behaviour assessment tool with good psychometric properties. METHODS: Data
      from 265 adults who were known to services were collected using a demographic
      survey tool and the Behavior Problems Inventory - Short Form. The prevalence of
      self-injurious, aggressive/destructive, stereotyped, and overall CB was
      evaluated. We explored the potential of developing cumulative risk indices (CRI)
      to inform longitudinal research and clinical practice. RESULTS: The prevalence of
      overall CB was 18.1% (95% CI: 13.94-23.19%). The prevalence of self-injurious
      behaviour was 7.5% (95% CI: 4.94-11.37%), aggressive-destructive behaviour 8.3%
      (95% CI: 5.54-12.25%), and stereotyped behaviour 10.9% (95% CI: 7.73-15.27%).
      Communication problems and severity of ID were consistently associated with
      higher risk of CBs. CRIs were significantly associated with CBs, and the five
      methods of CRI development produced similar results. CONCLUSIONS: Findings
      suggest a multi-element response to CB is likely to be required that includes
      interventions for communication and daytime activity. Exploratory analyses of
      CRIs suggested these show promise as simple ways to capture cumulative risk in
      this population. Subject to longitudinal replication, such a tool may be
      especially useful in clinical practice to identify adults who are priority for
      interventions and predict future demand on services. PRACTITIONER POINTS: The
      prevalence of challenging behaviour (CB) was 18.1% in this total population
      study. Stereotypy was the most frequent type of CB. Communication difficulties
      and severe-profound intellectual disabilities were most systematically related to
      the presence of CB. Establishing the effect of multiple risk factors is likely to
      identify people who are priority for interventions. Addressing multiple, rather
      than singular risks, is likely to be more efficacious. We tested five different
      methods of putting together a multiple risk index. All methods provided a
      reasonable association with CB. The most user-friendly method was the additive
      cumulative risk index (CRI). Limitations This is a cross-sectional design which
      enabled factors currently associated with CB to be identified for the whole
      cohort, but these variables may not be those conferring risk for the development
      or maintenance of CB over time. Future longitudinal research is required to
      replicate these CRI analyses before concluding about the CRI method with the
      highest predictive validity.

PMID- 27878841
TI  - Intraductal papillary mucinous neoplasms of the pancreas: reporting clinically
      relevant features.
AB  - Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can exhibit a
      wide spectrum of macroscopic and microscopic appearances. This not only causes
      occasional difficulties for the reporting pathologist in distinguishing these
      tumours from other lesions, but is also relevant clinically. As evidence
      accumulates, it becomes clear that multiple macroscopic and histological features
      of these neoplasms are relevant to the risk for malignant transformation and,
      consequently, of prime importance for clinical patient management. The need for
      detailed reporting is therefore increasing. This review discusses the panoply of
      gross and microscopic features of IPMN as well as the recommendations from recent
      consensus meetings regarding the pathology reporting on this tumour entity.

PMID- 27878842
TI  - Pharmacologic Treatment of Vitiligo in Children and Adolescents: A Systematic
      Review.
AB  - BACKGROUND: The true pathogenic mechanism of vitiligo is still unknown. About
      half of the patients with this disease have onset before the age of 20 years,
      making it a serious dermatologic disorder in childhood. OBJECTIVES: The objective
      of this study was to review the literature in a systematic way and identify the
      main pharmacologic treatments and outcomes in children and adolescents with
      vitiligo. METHODS: Four databases-the National Library of Medicine (MEDLINE
      PubMed), Web of Science, Scopus, and Latin American and Caribbean Health Sciences
      (LILACS)-were used for the search up to January 2015. All electronic search
      titles, selected abstracts and full-text articles were independently reviewed by
      a minimum of two reviewers. RESULTS: There were 15 articles from 13 different
      countries: 3 were retrospective and 12 were prospective; the number of
      participants in the studies varied between 9 and 400, ages ranged from 0 to 18
      years, and the duration of disease ranged from 1 to 17 years. The most commonly
      used drugs were tacrolimus alone (or combined with clobetasol), pimecrolimus,
      corticosteroids, and calcipotriol. Treatment duration ranged from 10 days to 6
      months with a topical route of administration. CONCLUSIONS: The main outcome
      measurements were morphometric analysis performed using a computer program,
      hematologic or biochemical change, and photography (predominant). It is unclear
      which was the most effective treatment for vitiligo, however, it was found that
      these therapies are all promising in the treatment of the disease. With proper
      care, disease control and repigmentation, even if partial, can be achieved.

PMID- 27878844
TI  - Factors influencing new graduate nurse burnout development, job satisfaction and
      patient care quality: a time-lagged study.
AB  - AIM: To test a hypothesized model linking new graduate nurses' perceptions of
      their manager's authentic leadership behaviours to structural empowerment, short
      staffing and work-life interference and subsequent burnout, job satisfaction and
      patient care quality. BACKGROUND: Authentic leadership and structural empowerment
      have been shown to reduce early career burnout among nurses. Short-staffing and
      work-life interference are also linked to burnout and may help explain the impact
      of positive, empowering leadership on burnout, which in turn influences job
      satisfaction and patient care quality. DESIGN: A time-lagged study of Canadian
      new graduate nurses was conducted. METHODS: At Time 1, surveys were sent to 3,743
      nurses (November 2012-March 2013) and 1,020 were returned (27.3% response rate).
      At Time 2 (May-July 2014), 406 nurses who responded at Time 1 completed surveys
      (39.8% response rate). Descriptive analysis was conducted in SPSS. Structural
      equation modelling in Mplus was used to test the hypothesized model. RESULTS: The
      hypothesized model was supported. Authentic leadership had a significant positive
      effect on structural empowerment, which in turn decreased both short-staffing and
      work-life interference. Short-staffing and work-life imbalance subsequently
      resulted in nurse burnout, lower job satisfaction and lower patient care quality
      1 year later. CONCLUSION: The findings suggest that short-staffing and work-life
      interference are important factors influencing new graduate nurse burnout.
      Developing nurse managers' authentic leadership behaviours and working with them
      to create and sustain empowering work environments may help reduce burnout,
      increase nurse job satisfaction and improve patient care quality.

PMID- 27878843
TI  - Mixed-method research protocol: defining and operationalizing patient-related
      complexity of nursing care in acute care hospitals.
AB  - AIM: To define the concept of patient-related complexity of nursing care in acute
      care hospitals and to operationalize it in a questionnaire. BACKGROUND: The
      concept of patient-related complexity of nursing care in acute care hospitals has
      not been conclusively defined in the literature. The operationalization in a
      corresponding questionnaire is necessary, given the increased significance of the
      topic, due to shortened lengths of stay and increased patient morbidity. DESIGN:
      Hybrid model of concept development and embedded mixed-methods design. METHODS:
      The theoretical phase of the hybrid model involved a literature review and the
      development of a working definition. In the fieldwork phase of 2015 and 2016, an
      embedded mixed-methods design was applied with complexity assessments of all
      patients at five Swiss hospitals using our newly operationalized questionnaire
      'Complexity of Nursing Care' over 1 month. These data will be analysed with
      structural equation modelling. Twelve qualitative case studies will be embedded.
      They will be analysed using a structured process of constructing case studies and
      content analysis. In the final analytic phase, the quantitative and qualitative
      data will be merged and added to the results of the theoretical phase for a
      common interpretation. Cantonal Ethics Committee Zurich judged the research
      programme as unproblematic in December 2014 and May 2015. DISCUSSION: Following
      the phases of the hybrid model and using an embedded mixed-methods design can
      reach an in-depth understanding of patient-related complexity of nursing care in
      acute care hospitals, a final version of the questionnaire and an acknowledged
      definition of the concept.

PMID- 27878845
TI  - Evaluation of raw acceleration sedentary thresholds in children and adults.
AB  - The aim was to develop sedentary (sitting/lying) thresholds from hip and wrist
      worn raw tri-axial acceleration data from the ActiGraph and GENEActiv, and to
      examine the agreement between free-living time spent below these thresholds with
      sedentary time estimated by the activPAL. Sixty children and adults wore an
      ActiGraph and GENEActiv on the hip and wrist while performing six structured
      activities, before wearing the monitors, in addition to an activPAL, for 24 h.
      Receiver operating characteristic (ROC) curves were used to determine sedentary
      thresholds based on activities in the laboratory. Agreement between developed
      sedentary thresholds during free-living and activPAL were assessed by Bland
      Altman plots and by calculating sensitivity and specificity. Using laboratory
      data and ROC-curves showed similar classification accuracy for wrist and hip
      thresholds (Area under the curve = 0.84-0.92). Greatest sensitivity (97-98%) and
      specificity (74-78%) were observed for the wrist thresholds, with no large
      differences between brands. During free-living, Bland-Altman plots showed large
      mean individual biases and 95% limits of agreement compared with activPAL, with
      smallest difference for the ActiGraph wrist threshold in children (+30 min, P =
      0.3). Sensitivity and specificity for the developed thresholds during free-living
      were low for both age groups and for wrist (Sensitivity, 68-88%, Specificity, 46
      59%) and hip placements (Sensitivity, 89-97%, Specificity, 26-34%). Laboratory
      derived sedentary thresholds generally overestimate free-living sedentary time
      compared with activPAL. Wrist thresholds appear to perform better than hip
      thresholds for estimating free-living sedentary time in children and adults
      relative to activPAL, however, specificity for all the developed thresholds are
      low.

PMID- 27878846
TI  - Are the classic signs of infection in concordance with results from percutaneous
      aspiration to diagnose infection in pressure injuries?
AB  - AIM: To explore the concordance between the presence of classic signs of
      infection and the positive diagnosis identified by the microbiological culture of
      fluid collected by percutaneous aspiration. BACKGROUND: The classic signs of
      infection are commonly applied in some contexts to confirm infection in pressure
      injuries, but its accuracy has been questioned in chronic wounds. Little is known
      about the concordance of this method with others, such as the deep fluid culture
      from pressure injuries collected by percutaneous aspiration. DESIGN: Multicentre,
      cross-sectional observational study. METHODS: Pressure injuries of patients from
      four health centres were analysed. Three types of data were recorded between
      February 2011 and March 2012: i) socio-demographic and clinical data, ii) number
      and type of infection signs and iii) microbiological results of deep fluid
      culture from injuries. The concordance was calculated with the kappa index to
      find a possible concordance between both methods. RESULTS: On 40.2% (n = 47) of
      injuries, two or more classic signs of infection or purulent exudate as unique
      sign were present, while the total positive results in the microbiological
      cultures were 50.4% (n = 59). The disparity of positive results, depending on the
      location and the stage of the pressure injury and the method applied, suggested a
      poor concordance between methods. The -0.092 kappa index confirmed the non
      concordance of the analysed methods. CONCLUSIONS: The tandem strategy is not
      useful to indicate an infection in pressure injuries. We advocate exploring other
      signs of infection and the adoption of other more reliable signs together with
      the classic signs of infection.

PMID- 27878847
TI  - Effectiveness of supporting intensive care units on implementing the guideline
      'End-of-life care in the intensive care unit, nursing care': a cluster randomized
      controlled trial.
AB  - AIM: The aim of this study was to examine the effectiveness of supporting
      intensive care units on implementing the guidelines. BACKGROUND: Quality of care
      can be achieved through evidence-based practice. Guidelines can facilitate
      evidence-based practice, such as the guidelines 'End-of-life care in the
      intensive care unit, nursing care'. Before intensive care nurses are able to use
      these guidelines, they needs to be implemented in clinical practice.
      Implementation is a complex process and may need support. DESIGN: Cluster
      randomized controlled trial. METHODS: Intensive care nurses of eight intensive
      care units in the intervention group followed a supportive programme that
      educated them on implementation, strategies, goals, project management and
      leadership. The intervention group focused on a stepwise approach to implement
      the guidelines. The control group (n = 5) implemented the guidelines
      independently or used the standard implementation plan supplementary to the
      guideline. The effectiveness of the programme was measured using questionnaires
      for nurses, interviews with nurses and a questionnaire for family of deceased
      patients, in the period from December 2014-December 2015. RESULTS: Overall, an
      increase in adherence to the guidelines was found in both groups. Overall, use of
      the guidelines in the intervention group was higher, but on some aspects the
      control group showed a higher score. Care for the patient and the overall nursing
      care scored significantly higher according to family in the intervention group.
      CONCLUSION: The increase in adherence to the guidelines and the significantly
      higher satisfaction of family in the intervention group indicate that the
      supportive programme had a more positive effect.

PMID- 27878848
TI  - The effectiveness of the COPE healthy lifestyles TEEN program: a school-based
      intervention in middle school adolescents with 12-month follow-up.
AB  - AIM: The goal of this study is to assess the applicability and long-term
      effectiveness of the T-COPE Healthy TEEN program on adolescent health.
      BACKGROUND: Obesity and mental health disorders are major public health problems
      in adolescents. In this context, including long-term and multiple behavioural
      obesity prevention programs are becoming increasingly important. DESIGN: A quasi
      experimental design with pre-test/post-test control group and repeated
      measurements. METHODS: Eighty-seven (45 in intervention group, 42 in control
      group) adolescents were included from two different middle schools in the
      intervention program. The data were analysed by using descriptive statistics,
      Pearson chi-square, Fisher's exact test, Student-t test, repeated measures of
      variance analysis and Cohen's d effect size. RESULTS: No significant difference
      was found between the intervention and control groups in terms of descriptive
      characteristics, behavioural and cognitive variables of the adolescents.
      Following the intervention, the adolescents in intervention groups showed
      improvements in nutritional behaviour, physical activity and stress management.
      These improvements concerned increased physical walking measured in the number of
      physical steps per week daily fruit and vegetable consumption and the daily
      quantity of water ingested. While their nutrition/physical activity knowledge
      significantly increased, their weight and anxiety symptoms significantly
      decreased. The effect of the program on body mass index, depression and health
      beliefs of the adolescents were not significant compared with the control group.
      CONCLUSION: The applicability of the T-COPE Healthy TEEN program on Turkish
      adolescents and its effectiveness on their health behaviours, nutrition and
      physical activity knowledge and stress management were revealed in this study.

PMID- 27878849
TI  - Leading change: a concept analysis.
AB  - AIM: To report an analysis of the concept of leading change. BACKGROUND: Nurses
      have been called to lead change to advance the health of individuals,
      populations, and systems. Conceptual clarity about leading change in the context
      of nursing and healthcare systems provides an empirical direction for future
      research and theory development that can advance the science of leadership
      studies in nursing. DESIGN: Concept analysis. DATA SOURCES: CINAHL, PubMed,
      PsycINFO, Psychology and Behavioral Sciences Collection, Health Business Elite
      and Business Source Premier databases were searched using the terms: leading
      change, transformation, reform, leadership and change. Literature published in
      English from 2001 - 2015 in the fields of nursing, medicine, organizational
      studies, business, education, psychology or sociology were included. METHODS:
      Walker and Avant's method was used to identify descriptions, antecedents,
      consequences and empirical referents of the concept. Model, related and contrary
      cases were developed. RESULTS: Five defining attributes of leading change were
      identified: (a) individual and collective leadership; (b) operational support;
      (c) fostering relationships; (d) organizational learning; and (e) balance.
      Antecedents were external or internal driving forces and organizational
      readiness. The consequences of leading change included improved organizational
      performance and outcomes and new organizational culture and values. CONCLUSION: A
      theoretical definition and conceptual model of leading change were developed.
      Future studies that use and test the model may contribute to the refinement of a
      middle-range theory to advance nursing leadership research and education. From
      this, empirically derived interventions that prepare and enable nurses to lead
      change to advance health may be realized.

PMID- 27878850
TI  - Analysis of morphological changes after facial massage by a novel approach using
      three-dimensional computed tomography.
AB  - BACKGROUND/PURPOSE: Photograph-based visual scoring has been used for evaluation
      of facial morphological changes. Here, we describe a three-dimensional computed
      tomography (3D-CT) method for objective analysis of facial and intra-facial
      (subcutaneous) changes. The effects of facial massage were examined using both
      methods. METHODS: Subjects were 12 healthy female volunteers without facial scars
      or deformation (age 30-54 years, mean 39.4 years). Photograph-based scoring of
      massage-induced morphological changes was done at the nasolabial folds, upper,
      lower and lateral cheeks and lower eyelids. For 3D-CT evaluation, the virtual
      center axis (VCA) was set as the cranio-caudal longitudinal line, and the VCA
      skin surface distances (VSDs) were measured. Massage-induced changes of VSD were
      calculated (facial massage-induced change rate, FMCR). Intra-facial
      (subcutaneous) changes were also evaluated. RESULTS: Photograph-based scoring
      revealed marked morphological changes of the nasolabial folds after facial
      massage, and changes of the lower, upper and lateral cheeks and lower eyelid were
      also observed in more than half of the subjects. FMCR values were significantly
      changed in the paranasal area, nasolabial fold area and cranial part of the
      mandibular area. Photograph-based scores at the lower cheek and lower eyelid were
      well correlated with FMCR in the inferior part of the nasolabial fold and the
      mandibular area, respectively. Massage-induced changes of subcutaneous fat
      tissues and facial expression muscles were also apparent on CT images.
      CONCLUSION: 3D-CT imaging is useful for objective evaluation of the effects of
      facial massage, including anatomical changes in subcutaneous structures.

PMID- 27878851
TI  - Exploring partners' perspectives on participation in heart failure home care: a
      mixed-method design.
AB  - AIM: To describe the partners' perspectives on participation in the care for
      patients with heart failure receiving home care. BACKGROUND: Partners are often
      involved in care of patients with heart failure and have an important role in
      improving patients' well-being and self-care. Partners have described both
      negative and positive experiences of involvement, but knowledge of how partners
      of patients with heart failure view participation in care when the patient
      receives home care is lacking. DESIGN: A convergent parallel mixed-method design
      was used, including data from interviews and questionnaires. METHODS: A
      purposeful sample of 15 partners was used. Data collection lasted between
      February 2010 - December 2011. Interviews were analysed with content analysis and
      data from questionnaires (participation, caregiving, health-related quality of
      life, depressive symptoms) were analysed statistically. Finally, results were
      merged, interpreted and labelled as comparable and convergent or as being
      inconsistent. RESULTS: Partners were satisfied with most aspects of
      participation, information and contact. Qualitative findings revealed four
      different aspects of participation: adapting to the caring needs and illness
      trajectory, coping with caregiving demands, interacting with healthcare providers
      and need for knowledge to comprehend the health situation. Results showed
      confirmatory results that were convergent and expanded knowledge that gave a
      broader understanding of partner participation in this context. CONCLUSION: The
      results revealed different levels of partner participation. Heart failure home
      care included good opportunities for both participation and contact during home
      visits, necessary to meet partners' ongoing need for information to comprehend
      the situation.

PMID- 27878853
TI  - A comparison of nursing tasks undertaken by regulated nurses and nursing support
      workers: a work sampling study.
AB  - AIMS: The aim of this study was to determine which tasks unregulated nursing
      support staff spend their work time undertaking and to determine differences
      between the work undertaken by licensed/regulated nurses on units which have
      nursing support workers and those on units which do not. BACKGROUND: Acute
      hospital nursing teams often include nursing support staff; little is known about
      what kinds of tasks these unregulated support workers do and how it affects the
      work tasks of their licensed/regulated team members. DESIGN: Cross-sectional
      analysis of nurse work sampling data. METHODS: Data collection took place between
      March-October 2013. The proportion of time spent on 25 work activities by nursing
      support staff and licensed/regulated nursing staff was compared. Logistic
      regression models estimated whether nursing support staff or licensed/regulated
      nurses were more likely to conduct direct and indirect patient care tasks and
      whether licensed/regulated nurses on units with nursing support staff were more
      likely to conduct direct or indirect tasks compared with those on units without
      nursing support workers. RESULTS: Nursing support staff spent the majority of
      their time engaged in direct care tasks, e.g. admission and assessment, hygiene
      and mobility. Although licensed/regulated nurses were less likely to undertake
      direct care tasks compared with support workers, those who worked on units with
      support workers undertook more direct care compared with those who worked on
      units without support workers. CONCLUSIONS: Nursing support workers were given
      tasks that required substantial amounts of patient interaction. These staff may
      be associated with an increase in direct care tasks for licensed/regulated
      nurses, who may duplicate the direct care done by nursing support workers.

PMID- 27878852
TI  - Optimal design of longitudinal data analysis using generalized estimating
      equation models.
AB  - Longitudinal studies are often applied in biomedical research and clinical trials
      to evaluate the treatment effect. The association pattern within the subject must
      be considered in both sample size calculation and the analysis. One of the most
      important approaches to analyze such a study is the generalized estimating
      equation (GEE) proposed by Liang and Zeger, in which "working correlation
      structure" is introduced and the association pattern within the subject depends
      on a vector of association parameters denoted by rho. The explicit sample size
      formulas for two-group comparison in linear and logistic regression models are
      obtained based on the GEE method by Liu and Liang. For cluster randomized trials
      (CRTs), researchers proposed the optimal sample sizes at both the cluster and
      individual level as a function of sampling costs and the intracluster correlation
      coefficient (ICC). In these approaches, the optimal sample sizes depend strongly
      on the ICC. However, the ICC is usually unknown for CRTs and multicenter trials.
      To overcome this shortcoming, Van Breukelen et al. consider a range of possible
      ICC values identified from literature reviews and present Maximin designs (MMDs)
      based on relative efficiency (RE) and efficiency under budget and cost
      constraints. In this paper, the optimal sample size and number of repeated
      measurements using GEE models with an exchangeable working correlation matrix is
      proposed under the considerations of fixed budget, where "optimal" refers to
      maximum power for a given sampling budget. The equations of sample size and
      number of repeated measurements for a known parameter value rho are derived and a
      straightforward algorithm for unknown rho is developed. Applications in practice
      are discussed. We also discuss the existence of the optimal design when an AR(1)
      working correlation matrix is assumed. Our proposed method can be extended under
      the scenarios when the true and working correlation matrix are different.

PMID- 27878854
TI  - Special issue - Bill Reynolds's Legacy.

PMID- 27878855
TI  - The personal cancer screening behaviours of nurses and midwives.
AB  - AIM: The aim of this study was to identify the personal cancer screening
      behaviours of nurses and midwives in New South Wales, Australia, and identify
      factors predictive of cancer screening uptake. BACKGROUND: The nursing workforce
      may have a higher risk for some cancers and is ageing. In Australia, more than
      40% are over 50 years - an age where cancer incidence rises rapidly, but when
      screening may reduce cancer mortality. Nurses and midwives are important health
      role models for the population, but their engagement in cancer screening is
      unknown. DESIGN: A cross-sectional survey conducted in 2014-2015. METHODS: Data
      were obtained from the 'Fit for the Future' study on 5041 working nurses and
      midwives in New South Wales, Australia and analyses were conducted on subsets of
      age-eligible respondents. Demographic, geographical and occupational data were
      analysed in relation to population-based screening for breast, cervical and bowel
      cancers and opportunistic screening for prostate and skin cancer screening
      participation, in line with Australian recommendations. RESULTS: Nurses' and
      midwives' recent screening rates were higher than the Australian general
      population across relevant age groups. Compared with full-time nurses and
      midwives, part-time/casual/pool workers were significantly more likely to
      undertake cervical, breast and bowel screening. Compared with those working
      office hours, shift workers were significantly less likely to undertake breast
      and bowel screening, but more likely to undertake skin screening. CONCLUSIONS:
      Disparities in reported screening prevalence and factors predictive of screening
      uptake indicate opportunities for targeted strategies to inform and/or promote
      workforce engagement with screening programmes and protect the health of this
      ageing workforce.

PMID- 27878856
TI  - A semiparametric mixture cure survival model for left-truncated and right
      censored data.
AB  - In follow-up studies, the disease event time can be subject to left truncation
      and right censoring. Furthermore, medical advancements have made it possible for
      patients to be cured of certain types of diseases. In this article, we consider a
      semiparametric mixture cure model for the regression analysis of left-truncated
      and right-censored data. The model combines a logistic regression for the
      probability of event occurrence with the class of transformation models for the
      time of occurrence. We investigate two techniques for estimating model
      parameters. The first approach is based on martingale estimating equations (EEs).
      The second approach is based on the conditional likelihood function given
      truncation variables. The asymptotic properties of both proposed estimators are
      established. Simulation studies indicate that the conditional maximum-likelihood
      estimator (cMLE) performs well while the estimator based on EEs is very unstable
      even though it is shown to be consistent. This is a special and intriguing
      phenomenon for the EE approach under cure model. We provide insights into this
      issue and find that the EE approach can be improved significantly by assigning
      appropriate weights to the censored observations in the EEs. This finding is
      useful in overcoming the instability of the EE approach in some more complicated
      situations, where the likelihood approach is not feasible. We illustrate the
      proposed estimation procedures by analyzing the age at onset of the occiput-wall
      distance event for patients with ankylosing spondylitis.

PMID- 27878857
TI  - Selective serotonin reuptake inhibitors and risk of major congenital anomalies
      for pregnancies in Japan: A nationwide birth cohort study of the Japan
      Environment and Children's Study.
AB  - We analyzed data from the Japan Environment and Children's Study (JECS), on the
      association between selective serotonin reuptake inhibitors (SSRI) use during
      pregnancy and the risk of developing of major congenital anomalies in Japan. JECS
      is an ongoing nationwide birth cohort study. The study includes 95 994 single
      pregnant women and their offspring. Among them, 172 used any SSRI up to the 12th
      gestational week. Crude analyses show a significantly increased incidence of
      upper limb, abdominal, and urogenital abnormalities. In particular, the incidence
      of microcephaly, hydrencephalus, esophageal atresia, small intestinal atresia,
      and achondroplasia was significantly higher with than without exposure to these
      substances. On multivariate analyses, urogenital abnormality was significant
      (odds ratio 3.227; 95% confidence interval: 1.460-7.134). This Japanese
      nationwide birth cohort survey clarified that the use of any SSRI until the 12th
      gestational week was associated with urogenital abnormality in children. The
      survey for association with minor classification abnormality needs further
      examination in Japan.

PMID- 27878858
TI  - Non-invasive tools for the diagnosis of cutaneous melanoma.
AB  - BACKGROUND: While the excisional biopsy and histological examination of
      suspicious lesions remains the current gold standard for diagnosing cutaneous
      melanoma (CM), there is a demand for more objective and non-invasive examination
      methods that may support clinicians in their decision when to biopsy or not.
      METHODS: This review is based on publications and guidelines retrieved by a
      selective search in PubMed and MEDLINE and focused on non-invasive diagnostic
      strategies for detecting melanoma. RESULTS: Ten different non-invasive techniques
      were compared with regard to applicability, status of development, and resources
      necessary for introduction into clinical routine (dermoscopy, sequential digital
      dermoscopy, total body photography, computer-aided multispectral digital
      analysis, electrical impedance spectroscopy, Raman spectroscopy, reflectance
      confocal microscopy, multiphoton tomography, stepwise two-photon-laser
      spectroscopy, quantitative dynamic infrared imaging). In an effort to create a
      classification based on our analyses, we suggest to differentiate i) tools for
      screening of patients in daily clinical routine, ii) tools for examination of a
      restricted number of preselected lesions that produce an automated diagnostic
      score, iii) tools for examination of a restricted number of preselected lesions
      at specialized centers requiring extensive training, iv) devices at an
      experimental stage of development. CONCLUSION: None of the discussed examination
      techniques is able to provide a definite and final diagnosis or to completely
      replace the histopathological examination. Up to date, the need for fully
      automated devices offering a complete skin cancer screening has not been
      satisfied.

PMID- 27878860
TI  - The role of menstruation in women's objectification: a questionnaire study.
AB  - AIM: The aim of this study was to investigate the concepts of objectification and
      self-objectification among young women in the context of attitudes towards
      menstruation, menstrual suppression, menstrual and menarche experiences, disorder
      eating and exercise habits and to detect predictors of objectification and self
      objectification. BACKGROUND: The negative effects of objectification are well
      founded. Considering the central role menstruation plays in female biology, it
      comes as quite a surprise that so little attention is given to the subject in the
      research on objectification. DESIGN: Cross-sectional explorative survey design.
      METHODS: A questionnaire that included the Self-Objectification Questionnaire,
      the Objectified Body Consciousness Scale, the Belief and Attitudes Towards
      Menstruation Questionnaire and the Suppress Menstruation subscale of the
      Attitudes Towards Menstrual Suppression Questionnaire was administered at the end
      of 2013 to 319 Icelandic women who represented the population by age. A stepwise
      multiple linear regression model was employed to calculate significant predictors
      of objectification and self-objectification. RESULTS: Four models of
      objectification are presented: the self-objectification model, the body
      surveillance model, the body shame model and the control belief model. Taken
      together, the strongest predictors of these models were related to eating habits.
      However, the findings also support the proposition that menstrual-related
      experiences influence women's objectification, particularly in terms of age at
      menarche, of belief in the prescriptive role of menstruation and of use of pain
      medication for menstrual pain. CONCLUSION: Healthcare providers in general and
      nurses in particular could and should assist girls and women in developing a
      positive view of their body and its reproductive functions by discussing the body
      and menstruation based on women's concerns.

PMID- 27878859
TI  - Paying patient and caregiver research participants: putting theory into practice.
AB  - AIM: To review and discuss the ethical and practical considerations about paying
      patient and caregiver participants in nursing research and, based on this review,
      to develop a set of guiding principles about payment of participants. BACKGROUND:
      To increase recruitment and retention, it is becoming increasingly common in
      nursing research to provide some form of payment to participants. The risk is
      that the promise of a payment may influence a patient or caregiver's decision to
      participate in research. However, research ethics protocols seldom provide
      explicit guidance about paying participants. Even where formal policies or fee
      schedules exist, there is little consistency in determining how payments should
      be calculated or administered. This has resulted in highly variable payment
      practices between locations, disciplines and institutions. DESIGN: Discussion
      paper. DATA SOURCES: PubMed, MEDLINE with Full Text, CINAHL and Health Source
      (Nursing/Academic Edition) were searched for terms related to paying research
      participants published between 2000 - August 2016. IMPLICATIONS FOR NURSING:
      Nurse researchers must comply with international, national and institutional
      ethical standards. Important ethical and practical considerations should guide
      the decision-making process about whether to pay research participants and how to
      determine the nature or value of the payment. Guiding principles can support
      researchers by highlighting key factors that may direct their decision-making in
      this regard. CONCLUSION: A deeper understanding of the fundamental ethical and
      practical considerations is needed to support researchers in their deliberations
      about paying participants in nursing research.

PMID- 27878862
TI  - Response to letter to the editor re. Hines J, Wilkinson SM, John SM, et al. The
      three moments of skin cream application: an evidence-based proposal for use of
      skin creams in the prevention of irritant contact dermatitis in the workplace.

PMID- 27878861
TI  - Endoscopic ultrasonography-guided biopsy using a Franseen needle design: Initial
      assessment.
AB  - BACKGROUND AND AIM: Recently, a 22-gauge (G) needle with a Franseen tip design
      was developed for endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB).
      The present study evaluated the performance of the Franseen biopsy needle in EUS
      guided tissue acquisition. METHODS: This is a retrospective study of patients who
      underwent EUS-FNB using the Franseen needle. Lesions were sampled using either
      the Franseen needle only or after failed diagnostic fine-needle aspiration (FNA).
      After rapid onsite evaluation (ROSE), two dedicated passes were carried out for
      histological assessment using the cell block technique. Main outcomes were: (i)
      rates of diagnostic adequacy for ROSE and histological diagnosis; and (ii)
      quality of histology as determined by total tissue area and tumor percentage in
      tissue. RESULTS: Thirty patients underwent EUS-FNB of pancreatic or other masses
      over a 3-month period. Twenty-four lesions were sampled using the Franseen needle
      only and six after failed diagnostic FNA. Final diagnosis was pancreatic cancer
      in 12, gastrointestinal stromal cell tumor in five, other tumors in four and
      benign disease in nine. Diagnostic adequacy for ROSE was 96.6% and histological
      diagnosis was established in 96.7% of patients. Median tissue area was 2.9 mm2
      (IQR = 0.68-8.71 mm2 ) and median tumor percentage in tissue was 73.9% (IQR = 44
      97.6). Rates of technical success and adverse events were 96.7 and 3.3%,
      respectively. CONCLUSION: Preliminary data suggest that the Franseen needle
      yields diagnostic material for ROSE and histology in >95% of patients.

PMID- 27878863
TI  - Formation Mechanism and Reversible Expansion and Shrinkage of Magnesium-Based
      Homochiral Metal-Organic Nanotubes.
AB  - Two pairs of homochiral magnesium phosphonates, namely (R)-, (S)-[Mg(pemp)(H2 O)2
      ] (1) and (R)-, (S)-Mg10 (pemp)10 (H2 O)10 ]?3 H2 O (2) are reported (pemp2- =(R)
      or (S)-(1-phenylethylamino) methylphosphonate). Compounds 1 show one-dimensional
      tubular structures. The tube wall is purely inorganic, containing six-membered
      rings made up of corner-sharing {MgO5 N} octahedra and {PO3 C} tetrahedra. The
      organic groups reside outside the tube. A bottom-up "direct growing" mechanism is
      proposed for the formation of the nanotubular structures of 1, based on the
      electrospray ionization mass spectrometry studies. Compounds 2 display two
      dimensional layered structures containing cross-linked squashed nanotubes.
      Interestingly, the two structures can interconvert reversibly upon temperature
      and pH modulation. This is the first report of a metal-organic nanotube that can
      shrink and recover in a reversible manner.

PMID- 27878864
TI  - Multidirectional Artificial Muscles from Nylon.
AB  - Multidirectional artificial muscles are made from highly oriented nylon
      filaments. Thanks to the low thermal conductivity of nylon and its anisotropic
      thermal expansion, bending occurs when a nylon beam is differentially heated.
      This heat can be generated via a Joule heating mechanism or high power laser
      pulses.

PMID- 27878866
TI  - From the Editors.

PMID- 27878865
TI  - Fibroblast growth factor 21 night watch: advances and uncertainties in the field.
AB  - Fibroblast growth factor (FGF) 21 belongs to a hormone-like subgroup within the
      FGF superfamily. The members of this subfamily, FGF19, FGF21 and FGF23, are
      characterized by their reduced binding affinity for heparin that enables them to
      be transported in the circulation and function in an endocrine manner. It is
      likely that FGF21 also acts in an autocrine and paracrine fashion, as multiple
      organs can produce this protein and its plasma concentration seems to be below
      the level necessary to induce a pharmacological effect. FGF21 signals via FGF
      receptors, but for efficient receptor engagement it requires a cofactor, membrane
      spanning betaKlotho (KLB). The regulation of glucose uptake in adipocytes was the
      initial biological activity ascribed to FGF21, but this hormone is now recognized
      to stimulate many other pathways in vitro and display multiple pharmacological
      effects in metabolically compromised animals and humans. Understanding of the
      precise physiology of FGF21 and its potential medicinal role has evolved
      exponentially over the last decade, yet numerous aspects remain to be defined and
      others are a source of debate. Here we provide a historical overview of the
      advances in FGF21 biology focusing on the uncertainties in the mechanism of
      action as well as the differing viewpoints relating to this intriguing protein.

PMID- 27878867
TI  - Erratum.

PMID- 27878868
TI  - Reproducible Risk Assessment.
AB  - Reproducible research is a concept that has emerged in data and computationally
      intensive sciences in which the code used to conduct all analyses, including
      generation of publication quality figures, is directly available, and preferably
      in open source manner. This perspective outlines the processes and attributes,
      and illustrates the execution of reproducible research via a simple exposure
      assessment of air pollutants in metropolitan Philadelphia.

PMID- 27878869
TI  - Effects of percutaneous endoscopic gastrostomy on survival of patients in a
      persistent vegetative state after stroke.
AB  - AIMS AND OBJECTIVES: To assess the effect of percutaneous endoscopic gastrostomy
      on short- and long-term survival of patients in a persistent vegetative state
      after stroke and determine the relevant prognostic factors. BACKGROUND: Stroke
      may lead to a persistent vegetative state, and the effect of percutaneous
      endoscopic gastrostomy on survival of stroke patients in a persistent vegetative
      state remains unclear. DESIGN: Prospective study. METHODS: A total of 97 stroke
      patients in a persistent vegetative state hospitalised from January 2009 to
      December 2011 at the Second Hospital, University of South China, were assessed in
      this study. Percutaneous endoscopic gastrostomy was performed in 55 patients, and
      mean follow-up time was 18 months. Survival rate and risk factors were analysed.
      RESULTS: Median survival in the 55 percutaneous endoscopic gastrostomy-treated
      patients was 17.6 months, higher compared with 8.2 months obtained for the
      remaining 42 patients without percutaneous endoscopic gastrostomy treatment.
      Univariate analyses revealed that age, hospitalisation time, percutaneous
      endoscopic gastrostomy treatment status, family financial situation, family care,
      pulmonary infection and nutrition were significantly associated with survival.
      Multivariate analysis indicated that older age, no gastrostomy, poor family care,
      pulmonary infection and poor nutritional status were independent risk factors
      affecting survival. Indeed, percutaneous endoscopic gastrostomy significantly
      improved the nutritional status and decreased pulmonary infection rate in
      patients with persistent vegetative state after stroke. Interestingly, median
      survival time was 20.3 months in patients with no or one independent risk factors
      of poor prognosis (n = 38), longer compared with 8.7 months found for patients
      with two or more independent risk factors (n = 59). CONCLUSION: Percutaneous
      endoscopic gastrostomy significantly improves long-term survival of stroke
      patients in a persistent vegetative state and is associated with improved
      nutritional status and decreased pulmonary infection. RELEVANCE TO CLINICAL
      PRACTICE: Percutaneous endoscopic gastrostomy is a promising option for the
      management of stroke patients in a persistent vegetative state.

PMID- 27878871
TI  - Hepatobiliary and Pancreatic: A hepatic mass involving diaphragm: A real
      malignancy?

PMID- 27878870
TI  - Epidermolysis bullosa simplex in sibling Eurasier dogs is caused by a PLEC non
      sense variant.
AB  - BACKGROUND: Plectin, a large linker protein found in many tissues, acts to
      connect components of the cytoskeleton to each other. In the epidermis, plectin
      binds keratin intermediate filaments to hemidesmosomes. A deficiency of plectin
      in the skin leads to blister formation in the basal layer and the disease
      epidermolysis bullosa simplex (EBS). HYPOTHESIS/OBJECTIVES: To describe a novel
      blistering disease that arose spontaneously in a litter of puppies. ANIMALS: Two
      female and one male 20-day-old Eurasier puppies, from a litter of six, were
      presented for evaluation of failure to thrive and then euthanized due to poor
      prognosis. The puppies had ulcers on the lips, tongue, nasal planum, paw pads and
      abdomen. RESULTS: Immunolabelling on frozen skin for basement membrane proteins
      revealed patchy and weak to absent staining for plectin as compared with strong
      linear staining in normal dogs. Ultrastructurally, hemidesmosomes were
      irregularly shaped and had loss of distinction between inner and outer plaques.
      Pedigree analysis supported an autosomal recessive mode of inheritance. A
      premature stop codon was discovered in exon 27 of PLEC that resulted in the
      production of a severely truncated protein. CONCLUSION: The study describes the
      first documented spontaneous EBS associated with a PLEC variant in domestic
      animals.

PMID- 27878872
TI  - Immobilizing Molecular Metal Dithiolene-Diamine Complexes on 2D Metal-Organic
      Frameworks for Electrocatalytic H2 Production.
AB  - Carbon electrocatalysts consisting of metal complexes such as MNx or MSx are
      promising alternatives to high-cost Pt catalysts for the hydrogen evolution
      reaction (HER). However, the exact HER active sites remain elusive. Here,
      molecular metal dithiolene-diamine (MS2 N2 , M=Co and Ni), metal bis(dithiolene)
      (MS4 ), and metal bis(diamine) (MN4 ) complexes were selectively incorporated
      into carbon-rich 2D metal-organic frameworks (2D MOFs) as model carbon
      electrocatalysts. The 2D MOF single layers, powders, and composites with graphene
      were thus prepared and showed definite active sites for H2 generation. The
      electrocatalytic HER activity of the 2D MOF-based catalysts with different metal
      complexes follow the order of MS2 N2 >MN4 >MS4 . Moreover, the protonation
      preferentially occurred on the metal atoms, and the concomitant heterolytic
      elimination of H2 was favored on the M-N units in the MS2 N2 active centers. The
      results provide an in-depth understanding of the catalytic active sites, thus
      making way for the future development of metal complexes in carbon-rich electrode
      materials for energy generation.

PMID- 27878874
TI  - Lymphocytes from patients with cutaneous T-cell lymphoma show DNA instability and
      reduced DNA repair using the Comet assay.

PMID- 27878873
TI  - The effects of spaced retrieval training in improving hyperphagia of people
      living with dementia in residential settings.
AB  - AIMS AND OBJECTIVES: To investigate the effectiveness of spaced retrieval for
      improving hyperphagia in patients with dementia in residential care settings.
      BACKGROUND: Although 10-30% of patients with dementia have hyperphagia, most
      studies have focused on eating difficulties. Only a few studies have focused on
      hyperphagia. Various memory problems cause hyperphagia in patients with dementia.
      Spaced retrieval, a cognitive technique for information learning, can be used as
      a training method to improve memory loss. Recent studies showed that patients who
      received the training successfully memorised information learned in the training
      and correctly applied it to their daily lives. STUDY DESIGN: Single-blind
      experiments were performed. METHODS: The 97 subjects with dementia were recruited
      from seven institutions. All research participants were stratified into three
      groups according to cognitive impairment severity and Hyperphagic Behavior Scale
      scores and then randomly assigned to the experimental and control groups. The
      experimental group received a six-week one-by-one spaced retrieval training for
      hyperphagia behaviour. The control group received routine care. RESULTS: After
      the intervention, the frequency and severity of hyperphagia in the patients with
      dementia, and food intake were significantly lower in the experimental group than
      in the control group. However, body mass index did not significantly differ.
      CONCLUSION: Our results suggest that the spaced retrieval training could decrease
      the frequency and severity of hyperphagia in patients with dementia. The content
      of this training programme is consistent with the normal manner of eating in
      daily life and is easy for patients to understand and perform. Therefore, it can
      be applied in residents' daily lives. RELEVANCE TO CLINICAL PRACTICE: This study
      confirms the efficacy of the spaced retrieval training protocol for hyperphagia
      in patients with dementia. In future studies, the follow-up duration can be
      increased to determine the long-term effectiveness of the intervention.

PMID- 27878875
TI  - Prevalence of amyloid deposits determined by fine-needle aspiration of abdominal
      fat in patients with psoriasis.

PMID- 27878876
TI  - Estimation of total genetic effects for survival time in crossbred laying hens
      showing cannibalism, using pedigree or genomic information.
AB  - Mortality of laying hens due to cannibalism is a major problem in the egg-laying
      industry. Survival depends on two genetic effects: the direct genetic effect of
      the individual itself (DGE) and the indirect genetic effects of its group mates
      (IGE). For hens housed in sire-family groups, DGE and IGE cannot be estimated
      using pedigree information, but the combined effect of DGE and IGE is estimated
      in the total breeding value (TBV). Genomic information provides information on
      actual genetic relationships between individuals and might be a tool to improve
      TBV accuracy. We investigated whether genomic information of the sire increased
      TBV accuracy compared with pedigree information, and we estimated genetic
      parameters for survival time. A sire model with pedigree information (BLUP) and a
      sire model with genomic information (ssGBLUP) were used. We used survival time
      records of 7290 crossbred offspring with intact beaks from four crosses. Cross
      validation was used to compare the models. Using ssGBLUP did not improve TBV
      accuracy compared with BLUP which is probably due to the limited number of sires
      available per cross (~50). Genetic parameter estimates were similar for BLUP and
      ssGBLUP. For both BLUP and ssGBLUP, total heritable variance (T2 ), expressed as
      a proportion of phenotypic variance, ranged from 0.03 +/- 0.04 to 0.25 +/- 0.09.
      Further research is needed on breeding value estimation for socially affected
      traits measured on individuals kept in single-family groups.

PMID- 27878877
TI  - Comments to: Hines J, Wilkinson SM, John SM, et al. The three moments of skin
      cream application: an evidence-based proposal for use of skin creams in the
      prevention of irritant contact dermatitis in the workplace. J Eur Acad Dermatol
      Venereol. 2016, Aug 22.

PMID- 27878879
TI  - Classificatory multiplicity: intimate partner violence diagnosis in emergency
      department consultations.
AB  - AIMS AND OBJECTIVES: To explore the naming, or classification, of physical
      assaults by a partner as 'intimate partner violence' during emergency department
      consultations. BACKGROUND: Research continues to evidence instances when intimate
      partner physical violence is 'missed' or unacknowledged during emergency
      department consultations. METHODS: Theoretically, this research was approached
      through complexity theory and the sociology of diagnosis. Research design was an
      applied, descriptive and explanatory, multiple-method approach that combined
      qualitative semistructured interviews with service-users (n = 8) and emergency
      department practitioners (n = 9), and qualitative and quantitative document
      analysis of emergency department health records (n = 28). RESULTS: This study
      found that multiple classifications of intimate partner violence were mobilised
      during emergency department consultations and that these different versions of
      intimate partner violence held different diagnostic categories, processes and
      consequences. CONCLUSION: The construction of different versions of intimate
      partner violence in emergency department consultations could explain variance in
      people's experiences and outcomes of consultations. The research found that the
      classificatory threshold for 'intimate partner violence' was too high.
      Strengthening systems of diagnosis (identification and intervention) so that all
      incidents of partner violence are named as 'intimate partner violence' would
      reduce the incidence of missed cases and afford earlier specialist intervention
      to reduce violence and limit its harms. RELEVANCE TO CLINICAL PRACTICE: This
      research found that identification of and response to intimate partner violence,
      even in contexts of severe physical violence, was contingent. By lowering the
      classificatory threshold so that all incidents of partner violence are named as
      'intimate partner violence', practitioners could make a significant contribution
      to reducing missed intimate partner violence during consultations and improving
      health outcomes for this population. This research has relevance for
      practitioners in any setting where service-user report of intimate partner
      violence is possible.

PMID- 27878878
TI  - Efficacy and safety of amphotericin B lipid-based formulations-A systematic
      review and meta-analysis.
AB  - Invasive fungal infections, an important cause of mortality, are primarily
      treated using amphotericin B, which is available in different formulations, both
      conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and
      Intralipid(r) infusion). The aim of our study was to determine the efficacy and
      safety of conventional amphotericin B vs its lipid-based formulations. A
      systematic review followed by pairwise meta-analysis was performed, including
      randomised controlled trials (RCTs) that evaluated the use of lipid-based
      amphotericin B in patients with any degree of immunosuppression and
      susceptibility to invasive fungal infection. An electronic search was conducted
      using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes
      were related to efficacy (cure) and safety (incidence of adverse events). Results
      were evaluated and meta-analyses were performed. Twenty-three RCTs were
      identified (n=2677 participants) for meta-analysis. No significant differences
      between conventional amphotericin B and any of the five formulations evaluated
      were observed, with regard to the efficacy analysis. With respect to the adverse
      events of nephrotoxicity, fever, chills and vomiting, all lipid formulations
      presented better profiles than the conventional formulation. The present
      systematic review and meta-analysis showed that conventional amphotericin B
      presents the same efficacy profile as lipid-based formulations, although the
      latter were associated with a safer profile.

PMID- 27878880
TI  - Highly Conformationally Restricted Cyclopropane Tethers with Three-Dimensional
      Structural Diversity Drastically Enhance the Cell Permeability of Cyclic
      Peptides.
AB  - The conformation of cyclic peptides is closely related to their physicochemical
      and biological properties, but their rational design to obtain a conformation
      with the desired properties is difficult. Herein, we present a new strategy by
      using conformationally restricted cyclopropane tethers (CPTs) to control the
      conformation and improve the cell permeability of cyclic peptides regardless of
      the amino acid sequence. Newly designed cis- or trans-CPTs with three-dimensional
      structural diversity were introduced into a model cyclic peptide, and the
      relationship between the conformation of the cyclic peptides and their cell
      permeability was analyzed. Peptides containing a CPT exhibited conformational
      diversity due to the characteristic steric feature of cyclopropane, among which
      peptides containing a CPT, cis-NfCf had remarkably higher cell permeability than
      peptides containing other CPTs-even superior to that of cyclosporine A, a known
      permeable cyclic peptide.

PMID- 27878881
TI  - Beneficial effect of extracellular adenosine 5'-triphosphate treatment on the
      Indochinese leopard (Panthera pardus delacouri) sperm quality after
      cryopreservation.
AB  - The Indochinese leopard (Panthera pardus delacouri) population, included in CITES
      Appendix I, has been declining for decades. Proper gamete preservation condition
      is critical for breeding programme management using artificial insemination or in
      vitro fertilization (IVF). The present study aimed at investigating the impact of
      post-thawing treatment of leopard semen with extracellular adenosine 5'
      triphosphate (ATPe) on sperm quality (including morphological traits and ability
      to fertilize an oocyte). Semen from six adult male leopards was collected by
      electroejaculation (one ejaculation per cat). After the evaluation of the fresh
      sample quality, the semen was cryopreserved (10 * 106 cells per straw; two straws
      per cat). After thawing, the sperm sample from the first straw of each cat was
      divided into three aliquots: control (no ATPe), supplemented with 1.0 or 2.5 mM
      ATPe that were evaluated for sperm quality at 10, 30 min and 3 hr post-thawing.
      The sperm sample from the second straw, supplemented with 0, 1.0 or 2.5 mM ATPe
      for 30 min, was assessed for IVF with domestic cat oocytes. Sperm quality (all
      metrics) was negatively affected by the cryopreservation process (p <= .05).
      However, the percentage of sperm motility, level of progressive motility and
      percentage of plasma membrane integrity did not differ (p > .05) among post
      thawing groups. The sperm mitochondrial membrane potential was enhanced (p <=
      .05) by ATPe treatment (1.0 and 2.5 mM; 10 min to 3 hr of incubation).
      Furthermore, incubation of ATPe (1.0 and 2.5 mM) for 30 min could promote sperm
      velocity patterns (curvilinear velocity; VCL and straight line velocity; VSL) (p
      <= .05). The percentage of pronuclear formation and cleaved embryos was increased
      (p <= .05) after 1.0 ATPe treatment (49.8 +/- 2.8; 45.9 +/- 1.5) compared to 0 mM
      (41.4 +/- 3.3; 38.9 +/- 0.5) whereas the number of sperm binding/oocyte did not
      significantly differ among groups. In summary, we suggest that ATPe activated the
      velocity of Indochinese leopard sperm motility that may lead to faster
      sperm/oocyte binding and sperm penetration (factors of successful embryo
      development).

PMID- 27878882
TI  - Tamoxifen may cause life-threatening angioedema attacks in patients with
      hereditary angioedema.

PMID- 27878884
TI  - Development of the Chinese version of Meaning in Life Scale for cancer patients
      and psychometric evaluation.
AB  - AIMS AND OBJECTIVES: To develop a Meaning in Life Scale for cancer patients in
      Chinese version and to test the validity and reliability. BACKGROUND: Meaning in
      life is a protective factor of psychological well-being and is negatively related
      to depression and demoralisation among cancer patients. The existing scales
      measuring meaning in life are mostly designed in English and there is no scale
      designed for Chinese cancer patients based on Chinese cultural background.
      DESIGN: Process of instrument development and psychometric evaluation were used.
      METHODS: Items were generated from literature review and a focus group interview.
      Delphi technique was used to test the content validity. Item analysis and
      exploratory factor analysis were performed with data from 251 cancer patients.
      The internal consistency of the scale was tested by Cronbach's alpha. RESULTS: A
      25-item Meaning in Life Scale in Chinese version with five domains was developed.
      The five factors explained 62.686% of the variance. The Cronbach's alpha for the
      total scale was 0.897. CONCLUSIONS: The Meaning in Life Scale in Chinese version
      has acceptable internal consistency reliability and good content validity and
      acceptable construct validity. The content of the scale reflected the attitudes
      of cancer patients towards meaning in life based on Chinese cultural background.
      RELEVANCE TO CLINICAL PRACTICE: The Chinese version of Meaning in Life Scale for
      Cancer Patients appears to be a new scale to assess meaning in life among Chinese
      cancer patients exactly and the concept of meaning in life presented in this
      scale provides new ideas of meaning intervention in routine clinical practice.

PMID- 27878883
TI  - School start time and sleep in Canadian adolescents.
AB  - Insufficient sleep is a serious problem in adolescents and school start time is
      thought to be a key contributor. This study provided the first comprehensive
      assessment of school start times across Canada and examined whether school start
      times were associated with sleep duration and tiredness among adolescents. We
      collected information on school start times from 362 schools that participated in
      the 2013/2014 Health Behaviour in School-aged Children study. We calculated sleep
      duration from weekday bedtime and wake time reported by 29 635 students (aged 10
      18 years). We classified weekday sleep as sufficient if it met national
      recommendations, and used data on self-reported tiredness at school in the
      morning. Random-effects regression models estimated the association of school
      start time with sleep duration, sleep sufficiency and tiredness. On average,
      schools started at 08:43 hours. Students slept an average of 8:36 h on weekdays
      and 69% met sleep duration recommendations, but 60% reported feeling tired in the
      morning. Every 10-min delay in school start time corresponded with 3.2 [95%
      confidence interval (CI): 2.0, 4.5] additional minutes of sleep, a 1.6% (95% CI:
      0.5, 2.8) greater probability of sufficient sleep and a 2.1% (95% CI: 1.0, 3.2)
      smaller probability of feeling tired at school in the morning. Students from
      schools that started later slept longer, were more likely to meet sleep
      recommendations and were less likely to report feeling tired in the morning. The
      study adds weight to the mounting evidence that delaying school start time
      benefits adolescent sleep.

PMID- 27878885
TI  - Beware when the hair turns dark again: clinical presentation and management of
      melanoma in situ in a giant congenital naevus on the scalp.

PMID- 27878886
TI  - Challenges in the nurse's role in rehabilitation contexts.
AB  - AIM AND OBJECTIVE: To shed light on how nurses perceive particular challenges
      that they experience in encounters with patients in rehabilitation wards.
      BACKGROUND: Rehabilitation is a tailor-made process that allows someone with
      impairment to live well. Many rehabilitation institutions embrace strong beliefs
      in patient participation as well as awareness of and listening to the needs and
      wishes of patients. To our knowledge, few studies have investigated the
      challenges encountered by nurses from patients in rehabilitation contexts and how
      these challenges might influence their roles as nurses. DESIGN AND METHODS: This
      study has a qualitative design that is based on three focus group interviews with
      nurses working in three rehabilitation wards. A convenience sample of 15 nurses,
      five from each ward, was recruited to participate in focus group interviews. The
      participants worked in wards for patients suffering mainly from stroke and head
      injuries. The analysis is inspired by hermeneutic principles to explore the
      participants' challenges in their role in rehabilitation contexts. RESULTS: Data
      analyses identified three main themes surrounding the challenges experienced by
      nurses: (1) Adjusting patients' and next of kin's expectations, (2) Tailoring
      support and information, (3) Recognising patients' knowledge. CONCLUSION: Our
      results from the three rehabilitation wards indicate that nurses display various
      educative strategies. There is, however, a need for further empirical work into
      how knowledgeable patients and next of kin create new challenges with
      implications for the nurse's role within rehabilitation contexts. RELEVANCE TO
      CLINICAL PRACTICE: The study highlights the educative aspects of the nurse's role
      in relation to patients and next of kin on rehabilitation wards as significant
      contributors to recovery processes.

PMID- 27878887
TI  - Why do young adults tan?

PMID- 27878888
TI  - Metabolomics Reveals that Momordica charantia Attenuates Metabolic Changes in
      Experimental Obesity.
AB  - Momordica charantia L., also known as bitter melon, has been shown to ameliorate
      obesity and insulin resistance. However, metabolic changes regulated by M.
      charantia in obesity are not clearly understood. In this study, serums obtained
      from obese and M. charantia-treated mice were analyzed by using gas and liquid
      chromatography-mass spectrometry, and multivariate statistical analysis was
      performed by Orthogonal partial least squares discriminant analysis. The results
      from this study indicated that body weight fat and insulin levels of obese mice
      are dramatically suppressed by 8 weeks of dietary supplementation of M.
      charantia. Metabolomic data revealed that overproductions of energy and nutrient
      metabolism in obese mice were restored by M. charantia treatment. The
      antiinflammatory and inhibition of insulin resistance effect of M. charantia in
      obesity was illustrated with the restoration of free fatty acids and eicosanoids.
      The findings achieved in this study further strengthen the therapeutic value of
      using M. charantia to treat obesity. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27878890
TI  - A qualitative exploration of anesthesia trainees' experiences during transition
      to a children's hospital.
AB  - BACKGROUND: The stresses of starting a new job can make anyone feel tired and
      inefficient. In health care, this may impair the ability to learn at a time when
      there is most to learn, and increase the risk of error in a context where errors
      may lead to patient harm. AIM: The aim of this study was to understand issues
      which influence anesthesia trainees' transition to a pediatric setting. METHODS:
      This qualitative study utilized in-depth semi-structured interviews to gather
      data from 31 anesthesia trainees who had commenced work at a tertiary children's
      hospital between 4 and 6 weeks previously. Data were examined using thematic
      analysis. RESULTS: Two key themes were identified: feeling ineffective, which
      appeared to have both a cognitive component (feeling disoriented) and an
      emotional component (feeling useless), and feeling anxious or afraid. Trainees
      found the pediatric environment highly unfamiliar, which made them feel
      disoriented, inefficient, and at times incompetent. Many experienced difficulty
      identifying a useful role in a highly specialized area of practice, leading to
      loss of identity as an expert clinician. Many described an ever-present fear of
      making an anesthetic error or being unable to manage a rapidly evolving clinical
      situation. Some trainees developed a negative mindset, which was reinforced by
      subsequent perceived failures. Overall, these experiences impeded trainees'
      ability to concentrate and learn. CONCLUSIONS: The impact of disorientation and
      anxiety on anesthesia trainees as they adapt to a highly specialized clinical
      environment such as a children's hospital should not be underestimated. Study
      findings illustrate the importance of helping new trainees to feel less afraid,
      more useful, and more realistic in assessing their own performance during the
      transition period.

PMID- 27878889
TI  - Decision making in drug safety-a literature review of criteria used to prioritize
      newly detected safety issues.
AB  - PURPOSE: In drug safety, there is a lack of guidance on how prioritization of
      safety issues should be performed. The aim of this literature review is to
      provide an overview of criteria used for signal prioritization and of the
      associated decision support frameworks. METHODS: A search strategy was
      constructed to identify relevant articles in Medline/Embase databases from the
      period from 1 January 1995 to 31 August 2015. The prioritization criteria were
      extracted and classified in relevant categories. RESULTS: From an initial set of
      63 articles, 11 were retained for full review. The articles mentioned 48 criteria
      used in the prioritization process, with a median of six criteria per study
      [range: 1-16]. More than half of the criteria (63%), referred to strength of
      evidence while 19% related to public health impact, 14% to general public and
      media attention and 4% to novelty of the drug event association. Fifteen criteria
      were tested for predictive value with 11 showing positive results, most of them
      from the strength of evidence category. Six decision-making frameworks are
      presented, which incorporate criteria from various categories. Five of these
      frameworks were tested against expert decisions or by other means, but only in
      one database each and for a limited set of products. CONCLUSIONS: There is a wide
      range of prioritization criteria described in the literature; however, few of
      them demonstrated predictive value. Many criteria with predictive value were
      related to strength of evidence category and to novelty. There were few attempts
      at integrating different criteria in decision support frameworks. Five of the
      frameworks were tested for validity and showed usefulness, while at least three
      are already in use for prioritization. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27878891
TI  - Cloning and characterization of the glutamate dehydrogenase gene in Streptococcus
      bovis.
AB  - Streptococcus bovis, an etiologic agent of rumen acidosis in cattle, is a rumen
      bacterium that can grow in a chemically defined medium containing ammonia as a
      sole source of nitrogen. To understand its ability to assimilate inorganic
      ammonia, we focused on the function of glutamate dehydrogenase. In order to
      identify the gene encoding this enzyme, we first amplified an internal region of
      the gene by using degenerate primers corresponding to hexameric family I and
      NAD(P)+ binding motifs. Subsequently, inverse PCR was used to identify the whole
      gene, comprising an open reading frame of 1350 bp that encodes 449 amino acid
      residues that appear to have the substrate binding site of glutamate
      dehydrogenase observed in other organisms. Upon introduction of a recombinant
      plasmid harboring the gene into an Escherichia coli glutamate auxotroph lacking
      glutamate dehydrogenase and glutamate synthase, the transformants gained the
      ability to grow on minimal medium without glutamate supplementation. When cell
      extracts of the transformant were resolved by blue native polyacrylamide gel
      electrophoresis followed by activity staining, a single protein band appeared
      that corresponded to the size of S. bovis glutamate dehydrogenase. Based on these
      results, we concluded that the gene obtained encodes glutamate dehydrogenase in
      S. bovis.

PMID- 27878893
TI  - Survival outcomes of consolidation chemoradiotherapy in esophageal cancer
      patients who achieve clinical complete response but refuse surgery after
      neoadjuvant chemoradiotherapy.
AB  - Some esophageal cancer patients may be reluctant to accept the scheduled
      resection after neoadjuvant chemoradiotherapy (nCRT) because of its potential
      negative impact on quality of life as a result of high morbidity. This study was
      performed to investigate the survival outcomes of these patients. Between 2000
      and 2012, we identified 190 patients with resectable esophageal squamous cell
      carcinoma (ESCC) who did not proceed to surgery following nCRT. Subjects who had
      a clinical complete response (cCR) and were medically fit for surgery were deemed
      eligible. Survival rates, recurrence patterns, and risk factors for recurrence
      served as the main outcome measures. The study cohort consisted of 73 patients
      (67 males and 6 females; mean age: 61.3 years). The 5-year overall survival was
      39.6% (median survival time: 46.77 months). Cancer recurrences were observed in
      44 patients (60.2%), with locoregional recurrence (LR) being the most common
      failure pattern (n = 35). Endoscopic findings after nCRT were the most important
      independent predictor of LR identified in multivariate analysis. Compared with
      the 'normal findings' subgroup, the odds ratios for LR in cCR patients who
      refused surgery were 4.774 (P = 0.026) and 2.844 (P = 0.16) in the 'scar' and
      'other findings' subgroups, respectively. Patients with 'normal findings' had the
      lowest rate of LR (22.2%), with no recurrences occurring within the first 6
      months. Sixty percent of ESCC patients who achieve cCR following nCRT but refuse
      esophagectomy develop disease recurrence, with LR being the most common pattern.
      Post-nCRT endoscopic findings may serve as a predictor for LR.

PMID- 27878892
TI  - Influence of SIGLEC9 polymorphisms on COPD phenotypes including exacerbation
      frequency.
AB  - BACKGROUND AND OBJECTIVE: The exacerbation-prone phenotype of COPD is
      particularly important, as exacerbations lead to poor quality of life and disease
      progression. We previously found that COPD patients who lack Siglec-14, a myeloid
      cell protein that recognizes bacteria and triggers inflammatory responses, are
      less prone to exacerbation. We hypothesized that the variations in other SIGLEC
      genes could also influence COPD exacerbation frequency, and investigated the
      association between SIGLEC9 polymorphisms and the exacerbation-prone phenotype of
      COPD. METHODS: We examined whether SIGLEC9 polymorphisms affect the frequency of
      COPD exacerbation in 135 subjects within our study population, and also analysed
      the correlation between the genotypes and the severity of airflow obstruction and
      emphysema in 362 Japanese smokers including 244 COPD patients. The association
      between these single nucleotide polymorphisms (SNPs) and COPD phenotypes were
      also assessed in a Caucasian population of ECLIPSE study. The effects of these
      coding SNPs (cSNPs) on Siglec-9 protein functions were analysed using in vitro
      assays. RESULTS: The G allele of rs2075803 and rs2075803 G/rs2258983 A(GA)
      haplotype in SIGLEC9 was associated with higher frequency of exacerbations and
      the extent of emphysema in COPD. These results did not replicate in the ECLIPSE
      study. A myeloid cell line expressing the Siglec-9 variant corresponding to GA
      haplotype produced more TNF-alpha than the one expressing the variant
      corresponding to the other major haplotype. CONCLUSION: The SIGLEC9 rs2075803
      G/rs2258983 A haplotype, which corresponds to a Siglec-9 variant that is less
      effective at suppressing inflammatory response, may be a risk factor for the
      development of emphysema.

PMID- 27878894
TI  - Downregulation of B-myb promotes senescence via the ROS-mediated p53/p21 pathway,
      in vascular endothelial cells.
AB  - OBJECTIVES: To reveal whether B-myb is involved in preventing senescence of
      vascular endothelial cells, and if so, to identify possible mechanisms for it.
      MATERIALS AND METHODS: C57/BL6 male mice and primary human aortic endothelial
      cells (HAECs) were used. Bleomycin was applied to induce stress-related premature
      senescence. B-myb knockdown was achieved using an siRNA technique and cell
      senescence was assessed using the senescence-associated beta-galactosidase (SA
      beta-gal) assay. Intracellular reactive oxygen species (ROS) production was
      analysed using an ROS assay kit and cell proliferation was evaluated using
      KFluor488 EdU kit. Capillary tube network formation was determined by Matrigel
      assay. Expressions of mRNA and protein levels were detected by real-time PCR and
      western blotting. RESULTS: B-myb expression significantly decreased, while p53
      and p21 expressions increased in the aortas of aged mice. This expression pattern
      was also found in replicative senescent HAECs and senescent HAECs induced by
      bleomycin. B-myb knockdown resulted in upregulation of p22phox , ROS accumulation
      and cell senescence of HAECs. Downregulation of B-myb significantly inhibited
      cell proliferation and capillary tube network formation and activated the p53/p21
      signalling pathway. Blocking ROS production or inhibiting p53 activation
      remarkably attenuated SA-beta-gal activity and delayed cell senescence induced by
      B-myb-silencing. CONCLUSION: Downregulation of B-myb induced senescence by
      upregulation of p22phox and activation of the ROS/p53/p21 pathway, in our
      vascular endothelial cells, suggesting that B-myb may be a novel candidate for
      regulating cell senescence to protect against endothelial senescence-related
      cardiovascular diseases.

PMID- 27878895
TI  - Polymorphisms of RDH16 and VEGFR1 influence M. trapezius steatosis in Japanese
      Black carcass.
AB  - The exact cause of steatosis, one of defects in Japanese beef carcasses, has not
      been elucidated to date, because it is very difficult to diagnose cyclopedically
      with certain reproducibility due to the bias in the outbreak. Therefore, the
      objective of this study was to assess the influence of polymorphisms in retinol
      dehydrogenase 16 (RDH16), myoferlin (MYOF) and vascular endothelial growth factor
      receptors 1 and 2 (VEGFR1, VEGFR2) on carcass-graded Musculus trapezius
      steatosis. For logistic regression analysis, 646 carcasses shipped from 29 farms
      in Miyazaki, Japan, were used. The GG genotype in RDH16 showed significant odds
      ratios against AA and AG. In VEGFR1, CT had a significant odds ratio against CC.
      After evaluating for interaction, highly significant odds ratios were observed in
      the combinations that included the GG risk genotype in RDH16. It is noteworthy
      that there was no steatosis in the combination GG (RDH16) and CC (VEGFR1). It may
      be concluded that there is a possibility that steatosis can be suppressed by the
      CC genotype in VEGFR1. The current study revealed the influence of genetic
      polymorphisms on M. trapezius steatosis that had not been reported until now, and
      may help elucidate the cause of steatosis.

PMID- 27878896
TI  - Bonding performance of universal adhesives to er,cr:YSGG laser-irradiated enamel.
AB  - Universal adhesives have been recently introduced for use as self-etch or etch
      and-rinse adhesives depending on the dental substrate and clinical condition.
      However, their bonding effectiveness to laser-irradiated enamel is still not well
      known. Thus, the aim of this study was to compare the shear bond strength (SBS)
      of universal adhesives (Single Bond Universal; Nova Compo-B Plus) applied to
      Er,Cr:YSGG laser-irradiated enamel with SBS of the same adhesives applied in self
      etch and acid-etching modes, respectively. Crown segments of sixty bovine
      incisors were embedded into standardized acrylic blocks. Flattened enamel
      surfaces were prepared. Specimens were divided into six groups according to
      universal adhesives and application modes randomly (n = 10), as follows: Single
      Bond Universal/acid-etching mode; Nova Compo-B Plus/acid-etching mode; Single
      Bond Universal/self-etching mode; Nova Compo-B Plus/self-etching mode; and Single
      Bond Universal/Er,Cr:YSGG Laser-etching mode; Nova Compo-B Plus/Er,Cr:YSGG Laser
      etching mode. After surface treatments, universal adhesives were applied onto
      surfaces. SBS was determined after storage in water for 24 h using a universal
      testing machine with a crosshead speed of 0.5 mm min-1 . Failure modes were
      evaluated using a stereomicroscope. Data was analyzed using two-way of analyses
      of variances (ANOVA) (p = 0.05). Two-way ANOVA revealed that adhesive had no
      effect on SBS (p = 0.88), but application mode significantly influenced SBS (p =
      0.00). Acid-etching significantly increased SBS, whereas there are no significant
      differences between self-etch mode and laser-etching for both adhesives. The bond
      strength of universal adhesives may depend on application mode. Acid etching may
      significantly increase bond strength, while laser etching may provide similar
      bond strength when compared to self-etch mode.

PMID- 27878897
TI  - Minimal immune determinants connect Zika virus, human Cytomegalovirus, and
      Toxoplasma gondii to microcephaly-related human proteins.
AB  - Aiming at the molecular definition of the relationship(s) between prenatal
      infections and fetal microcephaly and using pentapeptides as minimal immune
      determinants, we analyzed the peptide matching between proteins from infectious
      agents involved in microcephalic syndromes (namely Zika virus, human
      Cytomegalovirus, and Toxoplasma gondii) and human proteins that, when altered,
      have been specifically associated with microcephaly. We report that an unexpected
      high number of epitopic pentapeptides (ie, 34) are common to the three
      fetopathogenic agents and repeatedly occur throughout an important number of
      microcephaly-related human proteins. The data introduce the issue of multiple
      cross-reactivity into the etiology on ZIKV-associated pathologies. Indeed, the
      commonality of immune determinants might lead to a sequence of boostered immune
      responses if the host undergoes different fetopathogenic infections, thus
      temporally scanning a potential clinical progression toward brain malformations.
      At this juncture, the past history of maternal infections/vaccinations might
      dictate the fetal pathologic outcome.

PMID- 27878899
TI  - Conformational analysis of a modified RGD adhesive sequence.
AB  - The conformational preferences of the Arg-GlE-Asp sequence, where GlE is an
      engineered amino acid bearing a 3,4-ethylenedioxythiophene (EDOT) ring as side
      group, have been determined combining density functional theory calculations with
      a well-established conformational search strategy. Although the Arg-GlE-Asp
      sequence was designed to prepare a conducting polymer-peptide conjugate with
      excellent electrochemical and bioadhesive properties, the behavior of such hybrid
      material as adhesive biointerface is improvable. Results obtained in this work
      prove that the bioactive characteristics of the parent Arg-Gly-Asp sequence
      become unstable in Arg-GlE-Asp because of both the steric hindrance caused by the
      EDOT side group and the repulsive interactions between the oxygen atoms belonging
      to the backbone amide groups and the EDOT side group. Detailed analyses of the
      conformational preferences identified in this work have been used to re-engineer
      the Arg-GlE-Asp sequence for the future development of a new electroactive
      conjugate with improved bioadhesive properties. The preparation of this new
      conjugate is in progress. Copyright (c) 2016 European Peptide Society and John
      Wiley & Sons, Ltd.

PMID- 27878898
TI  - Feasibility and safety of peroral endoscopic myotomy for achalasia after failed
      endoscopic interventions.
AB  - With advances in natural orifice transluminal endoscopic surgery, peroral
      endoscopic myotomy (POEM) has become a novel treatment for esophageal achalasia.
      In this study, we investigated the feasibility and safety of POEM in patients
      with achalasia after failed endoscopic interventions. Data on all patients
      undergoing POEM treatment of achalasia were collected prospectively. We enrolled
      61 patients who underwent POEM for achalasia between July 2011 and January 2014.
      The preoperative intervention group included patients who had undergone botulinum
      toxin injection or pneumatic balloon dilation before POEM. The preoperative,
      operative, and short-term outcome data between the groups were compared. Among
      preoperative intervention group, 22 patients received endoscopic therapy before
      being referred for operation (18 dilation only, 2 botulinum toxin only, and 2
      both treatments). Procedure time in the preoperative intervention group was
      similar to the nonpreoperative intervention group (60.8 +/- 30.9 vs. 62.0 +/-
      21.0 minutes, P = 0.863). Both groups demonstrated significant improvement in
      Eckardt scores and manometric outcomes at 1-year follow-up. There were no
      significant differences in pretreatment and posttreatment D-values of symptom
      scores and lower esophageal sphincter pressures between groups (6.2 +/- 2.2 vs.
      6.1 +/- 1.8, P = 0.840; 27.9 +/- 17.6 vs. 24.9 +/- 15.2; P = 0.569). There was
      also no significant difference in the incidence of intraoperative complications
      (P = 0.958) and gastroesophageal reflux rate (23.5% vs. 20.0%, P = 0.771) between
      the two groups. Our study demonstrated that POEM is safe and effective, even for
      treating achalasia in the setting of failed endoscopic interventions.

PMID- 27878901
TI  - Radioactive cesium and potassium in cattle living in the 'zone in preparation for
      the lifting of the evacuation order' of the Fukushima nuclear accident.
AB  - To contribute to the reconstruction of livestock industry in Fukushima,
      radioactive cesium (134 Cs, 137 Cs) and potassium (4  degrees K) were measured in
      various tissues of beef cattle living in an area where the evacuation order will
      be lifted in the near future. Radioactive cesium concentration was less than 100
      Bq/kg in most of the samples. Skeletal muscles and kidney had the highest
      concentrations of radioactive cesium, whereas the liver was lowest among samples,
      excepting blood. Radioactive cesium concentration in the sirloin, tenderloin and
      top round was significantly higher than that in the neck muscle. Radioactive
      cesium concentration in the urine was not correlated with that in the blood, but
      the relationship became proportional when corrected with urinary 4  degrees K.
      Distribution of 4  degrees K was similar but not identical to that of radioactive
      cesium. These results suggest that it will be possible to resume livestock
      production in this area after the decontamination measures are completed and the
      evacuation order is lifted. Contamination level of living cattle can be estimated
      not only by blood samples but also by urine samples. If 50-100 Bq/kg of cesium is
      detected in the neck muscle at a slaughterhouse, the cattle should be reinspected
      using a sample from different muscles.

PMID- 27878903
TI  - Striking the Right Balance: Police Experience, Perceptions and Use of Independent
      Support Persons During Interviews Involving People with Intellectual Disability.
AB  - BACKGROUND: Several jurisdictions mandate the presence of an independent support
      person during police interviews with vulnerable people. The current study
      investigated police officers' experiences and perceptions of these volunteers
      during interviews with people with intellectual disability(ies) (ID). METHODS:
      The sample comprised 229 police officers who attended a mandatory firearms
      training course in Melbourne, Australia, in 2010. RESULTS: Participants commonly
      reported utilizing independent support persons and displayed a fair understanding
      of their role. Overall, volunteers were engaged more frequently than
      family/friends; police considered the volunteers to be more impartial during
      interviews, whereas family/friends provided a greater level of emotional support
      to interviewees. CONCLUSIONS: Independent support persons need to demonstrate two
      quite different types of support to people with intellectual disability(ies)
      during police interviews; these require quite different skill sets and suggest
      the need for more tailored training and support for these volunteers.
      Implications for future research and policy are discussed.

PMID- 27878900
TI  - Lesbian, gay and bisexual college student perspectives on disparities in weight
      related behaviours and body image: a qualitative analysis.
AB  - AIMS AND OBJECTIVES: To (1) explore college students' perceived sexual
      orientation-related barriers to engaging in physical activity, eating healthfully
      and maintaining healthy body images and (2) identify types of campus resources on
      physical activity, healthy eating and body image available to lesbian, gay and
      bisexual college students. BACKGROUND: Previous research has highlighted sexual
      orientation disparities in weight status, physical activity, healthy eating and
      body image. Despite this, little is known about the context surrounding these
      disparities. DESIGN: Cross-sectional study using individual interviews. METHODS:
      Thirty (15 males, 15 females) lesbian, gay, bisexual, queer and pansexual
      identified college students, aged 18-30 years participated in the study. Quasi
      inductive coding was used to analyse transcribed interview data and an iterative
      coding process was used to organise data into themes. RESULTS: Many felt their
      sexual orientation helped them be physically active, engage in healthful eating
      habits and have a positive body image. However, sexual orientation was also
      identified as a stressor that adversely impacted physical activity and eating
      habits. CONCLUSIONS: Lesbian, gay and bisexual students may have to negotiate
      their sexuality in ways that could adversely influence their physical activity,
      eating habits and body image. Both clinical and institutional interventions
      should be inclusive of all people, including lesbian, gay and bisexual, queer,
      and pansexual students. Further, tailored interventions to meet the specific
      health needs of sexual minority populations are needed. RELEVANCE TO CLINICAL
      PRACTICE: Clinicians need to understand the context in which sexual minority
      young adults experience health promotion messaging and programming. Clinic-based
      tailored interventions are critical as part of a multi-faceted approach in
      promoting physical activity and healthier eating habits for all young people,
      including lesbian, gay, bisexual, queer and pansexual, to more effectively
      address the prevention of chronic diseases.

PMID- 27878902
TI  - A retrospective comparison of intrathecal morphine and epidural hydromorphone for
      analgesia following posterior spinal fusion in adolescents with idiopathic
      scoliosis.
AB  - BACKGROUND: Posterior spinal fusion to correct idiopathic scoliosis is associated
      with severe postoperative pain. Intrathecal morphine is commonly used for
      analgesia after adolescent posterior spinal fusion; however, anticipating and
      managing the increase in pain scores after resolution of analgesic effect of
      intrathecal morphine analgesia is challenging. In 2014, we developed a clinical
      protocol detailing both the administration of intrathecal morphine
      intraoperatively and the transition to routine, scheduled oral analgesics at 18 h
      postoperatively. The goal of our study was to examine the efficacy of our
      intrathecal morphine protocol vs epidural hydromorphone for postoperative
      analgesia after posterior spinal fusion. METHODS: Following IRB approval, we
      retrospectively identified developmentally intact children of ages 10-20 years in
      our electronic database with a diagnosis of idiopathic scoliosis who had
      undergone elective posterior spinal fusion surgery from June 2014 to April 2015.
      For the intrathecal morphine group, intrathecal morphine was administered in a
      dose of 12 MUg.kg-1 (max 1000 MUg) prior to incision. Postoperatively, all
      children in the intrathecal morphine group had an order to receive oral oxycodone
      (0.1 mg.kg-1 , max 5 mg) starting at 18 h postintrathecal morphine injection. For
      the epidural hydromorphone group, catheters were placed by the surgeon and
      bolused with 5 MUg.kg-1 hydromorphone (max 200 MUg) and 1 MUg.kg-1 fentanyl (max
      50 MUg), followed by a continuous infusion of 40-60 MUg.h-1 , and patient
      controlled bolus doses of 5 MUg with a lockout interval of 30 min. All patients
      in both groups had postoperative orders for acetaminophen, diazepam, and
      ketorolac. RESULTS: During the study time period, 20 patients received
      intrathecal morphine and were successfully matched with 20 patients who received
      epidural hydromorphone. All patients in the intrathecal morphine group were
      transitioned to oral analgesics on the first postoperative day, without need for
      intravenous opioids after discharge from the postanesthesia care unit. Compared
      to the epidural hydromorphone group, the intrathecal morphine group reported
      lower pain scores in the postanesthesia care unit (difference in means -4.26 [95%
      CI -6.56, -1.96], P = 0.001) and first 8 h after surgery (difference in means 
      1.88 [95% CI -3.84, 0.082, P = 0.060) and higher pain scores on the 2nd
      postoperative day (difference in means 1.60 [95% CI 0.10, 3.10], P = 0.037). The
      documented time to ambulation and time of Foley catheter removal were
      statistically earlier in the intrathecal morphine group, and the hospital length
      of stay was significantly shorter (3.0 +/- 0.5 days vs 3.5 +/- 0.7 days; P =
      0.03). Adverse events did not significantly differ between the groups.
      CONCLUSION: The efficacy of intraoperative intrathecal morphine for postoperative
      analgesia in the posterior spinal fusion patient population has been shown
      previously; however, the pain and analgesic trajectory, including transition to
      other analgesics, has not previously been studied. Our findings suggest that for
      many patients, use of intrathecal morphine in addition to routine administration
      of nonopioid medications facilitates direct transition to oral analgesics in the
      early postoperative period and earlier routine ambulation and discharge of
      posterior spinal fusion patients.

PMID- 27878904
TI  - Venous thromboembolism in patients with esophageal or gastric cancer undergoing
      neoadjuvant chemotherapy.
AB  - There is a well-established link between cancer and venous thromboembolism (VTE),
      and patients receiving chemotherapy for esophageal or gastric cancer appear at
      high risk of developing VTE. The incidence of VTE in the neoadjuvant setting in
      these patients is poorly understood, as is the role for thromboprophylaxis during
      neoadjuvant chemotherapy. A PubMed search was conducted using a combination of
      terms including; esophageal & gastric cancer, deep venous thrombosis (DVT), VTE,
      neoadjuvant, chemotherapy and chemoradiotherapy. One hundred and fifty-four
      articles were retrieved and a narrative review was conducted. For patients with
      esophageal and gastric cancer the incidence of VTE ranged from 4 to 19%. Gastric
      cancer (Odds Ratio [OR] 6.38, [95% CI: 1.96-20.80]) and Stage III/IV disease, (OR
      5.16 [95% CI: 1.29-20.73]) were identified as risk factors for developing VTE.
      Neoadjuvant chemotherapy was identified as an independent risk factor for
      developing VTE. Symptomatic and asymptomatic VTE have a similar effect on
      mortality. Median overall survival for asymptomatic VTE was 13.9 months (95% CI:
      5.0-infinity) versus 12.8 months (95% CI: 4.7-30.3) if the VTE was symptomatic.
      Neoadjuvant chemotherapy is a significant risk factor for VTE in patients with
      esophageal and gastric cancer. Intervention to minimize the risk using
      pharmacological and mechanical thromboprophylaxis should be considered, and this
      should start in the neoadjuvant period.

PMID- 27878905
TI  - Effects of labial adhesion on maxillary arch dimensions and nasolabial esthetics
      in cleft lip and palate: a systematic review.
AB  - Labial adhesion is a preliminary surgical lip approximation used in the early
      management of unilateral and bilateral cleft lip and palate. Our objective was to
      evaluate its effects on the maxillary arch dimensions and nasolabial esthetics by
      means of a systematic review. The literature search (1955-2016) was based on
      MEDLINE via PubMed, Web of Science, EMBASE, and the Cochrane Library. Studies
      with labial adhesion as a single preliminary step for definitive lip closure, in
      combination with nasoalveolar molding or in combination with infant orthopedics
      were considered eligible. Fifteen articles were identified (1978-2015), including
      587 patients who underwent labial adhesion. Reduction in alveolar cleft width was
      between 60.9% and 100% in unilateral cases and between 47.5% and 100% in
      bilateral cases. Reduction in palatal cleft width was between 28.4% and 59.8% in
      unilateral cases and between 37.5% and 50.5% in bilateral cases. No conclusive
      results could be drawn about the effect on nasolabial esthetics. This systematic
      review comprises the available literature of the last 50 years about labial
      adhesion. It showed reduction of alveolar and palatal cleft width after a
      treatment with labial adhesion with or without infant orthopedics. The treatment
      effect on nasolabial esthetics, especially in the long term, remains unclear.

PMID- 27878906
TI  - Simeprevir, daclatasvir and sofosbuvir for hepatitis C virus-infected patients
      with decompensated liver disease.
AB  - Approximately three million individuals in the United States are chronically
      infected with hepatitis C virus (HCV). Chronic HCV infection may lead to the
      development of compensated as well as decompensated liver cirrhosis. The Phase II
      IMPACT study was conducted in HCV genotype 1- or 4-infected cirrhotic patients
      with portal hypertension or decompensated liver disease and assessed for the
      first time the combination of the three direct-acting antivirals simeprevir,
      daclatasvir and sofosbuvir. Treatment-naive or treatment-experienced adults with
      Child-Pugh (CP) score <7 (CP A) and evidence of portal hypertension, or CP score
      7-9 (CP B), received 12 weeks of simeprevir 150 mg, daclatasvir 60 mg and
      sofosbuvir 400 mg, once daily. The primary efficacy endpoint was sustained
      virologic response 12 weeks after end of treatment (SVR12). Pharmacokinetics and
      safety were also assessed. Overall, 40 patients were enrolled (CP A: 19; CP B:
      21). All 40 patients achieved SVR12. At week 8, the mean pharmacokinetic exposure
      to simeprevir, sofosbuvir, daclatasvir and GS-331007 (sofosbuvir metabolite) was
      2.2-, 1.5-, 1.2- and 1.2-fold higher in patients with CP B than CP A,
      respectively. Grade 1/2 adverse events (AEs) occurred in 26 of 40 (65%) patients.
      One CP B patient had a Grade 3 AE (gastrointestinal haemorrhage), which was
      reported as a serious AE but not considered related to study drugs. Treatment for
      12 weeks with simeprevir, daclatasvir and sofosbuvir was generally safe and well
      tolerated, and resulted in 100% of cirrhotic patients with portal hypertension or
      decompensated liver disease achieving SVR12.

PMID- 27878907
TI  - From Childhood Trauma to Self-Harm: An Investigation of Theoretical Pathways
      among Female Prisoners.
AB  - BACKGROUND: Despite empirical evidence suggesting complex associations between
      childhood trauma and self-harm, there is a dearth of research investigating this
      association in the female prison population. The current study explored pathways
      to self-harm following childhood trauma, by investigating the mediating roles of
      Post-traumatic Stress Disorder (PTSD) symptoms, emotion regulation and
      dissociation, in this relationship, within a sample of 89 female prisoners.
      METHODS: Cross-sectional, interview-format, questionnaire study within a female
      prison population. Measures of childhood trauma, self-harm, PTSD, emotion
      regulation and dissociation were administered. RESULTS: The majority of the
      sample (58.4%) reported history of self-harm. Bootstrapped mediation analyses
      indicated an indirect effect of emotion regulation on the relationship between
      childhood trauma and self-harm. An indirect effect was also found for PTSD
      arousal/reactivity cluster of symptoms. Multiple mediation analyses revealed that
      interactional effects were present for emotion regulation and arousal/reactivity,
      and emotion regulation and dissociation, respectively. CONCLUSION: Self-harm is
      highly prevalent among female prisoners. Interventions promoting emotion
      regulation and addressing arousal/reactivity symptoms following traumatization
      may provide an effective way of addressing this problem. Copyright (c) 2016 John
      Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGES: Self-harm is highly prevalent
      amongst female prisoners, occurring in 58.4% of this sample. Emotion regulation
      and the arousal/reactivity symptom cluster of PTSD were found to mediate the
      relationship between childhood trauma and self-harm, both independently and
      simultaneously. Emotion regulation and dissociation were found to interactionally
      mediate this relationship. Strategies targeting emotion dysregulation and
      hyperarousal symptoms, amongst female prisoners who have experienced childhood
      trauma, may be helpful in reducing self-harming behaviours.

PMID- 27878908
TI  - Parents with Intellectual Disabilities Experiencing Challenging Child Routines: A
      Pilot Study Using Embedded Self-Determination Practices.
AB  - BACKGROUND: Practices to facilitate self-determination have not received
      appropriate attention in research concerning parents with intellectual
      disabilities (ID). Likewise, parenting interventions for adults with intellectual
      disabilities have seldom observed both parent and child behavioural outcomes.
      METHODS: This study evaluated the effectiveness of a parenting intervention
      embedded with self-determination facilitation practices for two dyads of a parent
      with intellectual disabilities and their young child. The interventions focused
      on increasing parents' ability to correctly implement steps of a parenting
      routine while reducing occurrence of challenging child behaviour. RESULTS: The
      results of the study demonstrated two basic effects of correctly completed steps
      of the parenting routine and a reduction of challenging child behaviour. Parents
      also reported decreased feelings of stress during the routine following
      completion of the intervention. CONCLUSIONS: Implications for future research and
      replication of this pilot study are discussed.

PMID- 27878909
TI  - Role of MCP-1 in pleural effusion development in a carrageenan-induced murine
      model of pleurisy.
AB  - BACKGROUND AND OBJECTIVE: Exudative pleural effusions affect over 1500 patients
      per million population each year. The pathobiology of pleural exudate formation
      remains unclear. Our recent study revealed monocyte chemotactic protein-1 (MCP-1)
      as a key driver of fibrinolytic-induced exudate effusion while another study
      found a role for MCP-1 in malignant effusion formation. In the present study, we
      further evaluated the role of MCP-1 in the development of pleural effusion in a
      mouse model of acute pleural inflammation. METHODS: lambda-Carrageenan (CAR) was
      injected into the pleural cavity of CD1 mice and pleural effusion volume measured
      up to 16 h post-injection. Pleural effusion and serum protein and MCP-1
      concentrations were measured and differential cell counts performed in fluids.
      Mice were also treated with either intraperitoneal (i) anti-MCP-1 antibody or
      isotype control or (ii) an MCP-1 receptor (CCR2) antagonist or vehicle control 12
      h prior to and at the time of CAR injection. RESULTS: Intrapleural CAR induced
      significant pleural fluid accumulation (300.0 +/- 49.9 MUL) in mice after 4 h.
      Pleural fluid MCP-1 concentrations were significantly higher than corresponding
      serum MCP-1 (144 603 +/- 23 204 pg/mL vs 3703 +/- 801 pg/mL, P < 0.0001). A
      significant decrease in pleural fluid formation was seen both with anti-MCP-1
      antibody (median (interquartile range, IQR): 36 (0-168) MUL vs controls 290 (70
      436) MUL; P = 0.02) or CCR2 antagonist (153 (30-222) MUL vs controls 240 (151
      331) MUL, P = 0.0049). CONCLUSIONS: Blockade of MCP-1 activity significantly
      reduced inflammatory pleural effusion formation in a CAR model. Together with
      recent successes in MCP-1 blockade in other effusion formation models, our data
      strongly support clinical evaluation of MCP-1 antagonists as a novel approach to
      pleural fluid management.

PMID- 27878910
TI  - Mothering with an Intellectual Disability: A Phenomenological Exploration of
      Making Infant-Feeding Decisions.
AB  - BACKGROUND: Mothers with intellectual disability are less likely than mothers
      without intellectual disability to breastfeed their infants, but there is little
      literature that addresses infant-feeding decisions among this population. This
      study explores experiences of mothers with intellectual disability in making and
      carrying out infant-feeding decisions. METHODS: Using a phenomenological
      approach, in-depth interviews were conducted with four mothers with intellectual
      disability. RESULTS: Analysis focused on making and carrying out infant-feeding
      decisions. Three sub-themes of making infant-feeding decisions emerged: being
      familiar with benefits of breastfeeding, owning the initial decision and
      preparing for infant-feeding. Two sub-themes of carrying out infant-feeding
      decisions transpired: facing challenges and receiving support. CONCLUSIONS: The
      prenatal period was a crucial time for the mothers regarding infant-feeding
      decisions. It is the time in which they felt the most decision-making power, yet
      opportunities to prepare for possible challenges were missed.

PMID- 27878911
TI  - Effect of increased feeding of dietary alpha-linolenic acid by grazing on
      formation of the cis9,trans11-18:2 isoform of conjugated linoleic acid in bovine
      milk.
AB  - Feeding systems such as grazing affect the fatty acid profile of bovine milk fat.
      In addition, milk fat is formed as the product of fatty acid metabolism in cow
      bodies before being secreted into milk. However, how grazing influences milk
      fatty acid profile through the metabolism has not been completely characterized.
      When fatty acid concentrations in Holstein milk were compared between grazing and
      non-grazing periods, alpha-linolenic acid was significantly higher in the grazing
      period than in the non-grazing period. This could be explained with an increase
      in alpha-linolenic acid feeding with grazing. alpha-linolenic acid had a linear
      positive correlation with conjugated linoleic acid (9c,11t-18:2) (CLA) and
      vaccenic acid (VA) during the grazing period, whereas CLA had higher correlation
      with linoleic acid rather than with alpha-linolenic acid during the non-grazing
      period. These data indicate that the high content of dietary alpha-linolenic acid
      affects CLA and VA formation in milk of grazing periods via alpha-linolenic acid
      metabolism into VA.

PMID- 27878912
TI  - Maternal Sensitivity in Mothers with Mild Intellectual Disabilities is Related to
      Experiences of Maltreatment and Predictive of Child Attachment: A Matched
      Comparison Study.
AB  - BACKGROUND: Scientific knowledge on the quality of caregiving/maternal
      sensitivity among mothers with mild intellectual disabilities (ID) is limited and
      subject to many methodological shortcomings, but seems to suggest that these
      mothers are less sensitive than mothers without intellectual disabilities.
      METHODS: In this matched-comparison study (N = 48), the present authors observed
      maternal sensitivity for 20 min in four different laboratory play situations. The
      study also included semi-structured interviews to assess maternal experiences of
      maltreatment and child attachment. RESULTS: The present authors found
      significantly lower sensitivity among mothers with intellectual disabilities than
      among a comparison group of mothers without intellectual disabilities. Among
      mothers with intellectual disabilities, low sensitivity was related to maternal
      experiences of maltreatment and predictive of disorganized child attachment. In
      the comparison group, high maternal sensitivity was related to partner presence
      and social support, and predictive of child intelligence. CONCLUSIONS: The
      present authors highlight the importance of attending to intellectual
      disabilities mothers' history of receiving care to understand their capacity for
      giving adequate care.

PMID- 27878913
TI  - Response of an ovine laryngeal injury model to a novel fibrosis inhibitor.
AB  - BACKGROUND: Vocal fold injury results in severe voice alteration that limits
      occupational function and social interaction. An ovine model of laryngeal injury
      has been developed, validated and utilized to examine laryngeal wound healing and
      the effect of a novel collagen inhibitor (halofuginone) on surgical wound
      healing. The study design includes basic research and animal model. METHODS: An
      ovine laryngeal model was utilized to study controlled vocal fold injury and
      healing. Twenty-five sheep were divided into five groups. Sheep underwent right
      vocal fold injury preceded or followed by administration of halofuginone orally,
      topically or intralesionally. Biopsies were taken at commencement, 1 month and
      larynges explanted at 3 months. Specimens were examined for elastin and collagen
      density and epithelial changes. Pearson correlation statistics and Student's t
      tests were used to assess inter-relationships. RESULTS: All sheep tolerated
      halofuginone. One sheep death occurred in an untreated sheep. Vocal fold tissue
      demonstrated a predictable histological response to injury. Elastin was
      significantly reduced post-injury in the glottis. Halofuginone administered
      orally for 10 weeks prevented elastin loss and demonstrated a trend of reducing
      collagen density post-injury. CONCLUSION: In an ovine laryngeal injury model,
      administration of a fibrosis inhibitor resulted in altered elastin and collagen
      deposition after injury in the glottis. Further investigation is warranted to
      examine whether these tissue changes affect vocal fold dynamics.

PMID- 27878914
TI  - Severe hypoglycemia rates are not associated with HbA1c: a cross-sectional
      analysis of 3 contemporary pediatric diabetes registry databases.
AB  - OBJECTIVE: To examine the association between glycated hemoglobin (HbA1c) and
      severe hypoglycemia rates in patients with type 1 diabetes receiving usual care,
      by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian
      Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children
      Diabetes Database (WACDD) diabetes registries. METHODS: Data for patients with
      type 1 diabetes, aged <18 years with a minimum duration of diabetes of 2 years,
      were extracted from each registry for a 12-month observation period between 2011
      and 2012 (7,102 T1DX, 18,887 DPV, and 865 WACDD). Rates of severe hypoglycemia
      (self-reported loss of consciousness/convulsion) were estimated per 100 patient
      years and analyzed by HbA1c, source registry, treatment regimen, and age group.
      RESULTS: Overall, the severe hypoglycemia rate per 100 patient years was 7.1,
      3.3, and 6.7 in T1DX, DPV, and WACDD patients, respectively. Lower HbA1c was not
      associated with an increased rate of severe hypoglycemia when examined by source
      registry, treatment regimen, or age group. CONCLUSION: An inverse relationship
      between mean HbA1c and risk of severe hypoglycemia was not observed in this study
      of 3, independent cohorts of children and adolescents with type 1 diabetes.
      Investigation in other large, longitudinal cohorts is recommended to further
      characterize the contemporary relationship between glycemic control and risk of
      severe hypoglycemia rates in pediatric patients with type 1 diabetes.

PMID- 27878915
TI  - Plant-phytopathogen interactions: bacterial responses to environmental and plant
      stimuli.
AB  - Plant pathogenic bacteria attack numerous agricultural crops, causing devastating
      effects on plant productivity and yield. They survive in diverse environments,
      both in plants, as pathogens, and also outside their hosts as saprophytes. Hence,
      they are confronted with numerous changing environmental parameters. During
      infection, plant pathogens have to deal with stressful conditions, such as
      acidic, oxidative and osmotic stresses; anaerobiosis; plant defenses; and contact
      with antimicrobial compounds. These adverse conditions can reduce bacterial
      survival and compromise disease initiation and propagation. Successful bacterial
      plant pathogens must detect potential hosts and also coordinate their possibly
      conflicting programs for survival and virulence. Consequently, these bacteria
      have a strong and finely tuned capacity for sensing and responding to
      environmental and plant stimuli. This review summarizes our current knowledge of
      the signals and genetic circuits that affect survival and virulence factor
      expression in three important and well-studied plant pathogenic bacteria with
      wide host ranges and the capacity for long-term environmental survival. These
      are: Ralstonia solanacerarum, a vascular pathogen that causes wilt disease;
      Agrobacterium tumefaciens, a biotrophic tumorigenic pathogen responsible for
      crown gall disease and Dickeya, a brute force apoplastic pathogen responsible for
      soft-rot disease.

PMID- 27878916
TI  - Can the outcomes of mesenchymal stem cell-based therapy for myocardial infarction
      be improved? Providing weapons and armour to cells.
AB  - Use of mesenchymal stem cell (MSC) transplantation after myocardial infarction
      (MI) has been found to have infarct-limiting effects in numerous experimental and
      clinical studies. However, recent meta-analyses of randomized clinical trials on
      MSC-based MI therapy have highlighted the need for improving its efficacy. There
      are two principal approaches for increasing therapeutic effect of MSCs: (i)
      preventing massive MSC death in ischaemic tissue and (ii) increasing production
      of cardioreparative growth factors and cytokines with transplanted MSCs. In this
      review, we aim to integrate our current understanding of genetic approaches that
      are used for modification of MSCs to enable their improved survival, engraftment,
      integration, proliferation and differentiation in the ischaemic heart. Genetic
      modification of MSCs resulting in increased secretion of paracrine factors has
      also been discussed. In addition, data on MSC preconditioning with physical,
      chemical and pharmacological factors prior to transplantation are summarized. MSC
      seeding on three-dimensional polymeric scaffolds facilitates formation of both
      intercellular connections and contacts between cells and the extracellular
      matrix, thereby enhancing cell viability and function. Use of genetic and non
      genetic approaches to modify MSC function holds great promise for regenerative
      therapy of myocardial ischaemic injury.

PMID- 27878917
TI  - Subjective well-being of mental health nurses in the United Kingdom: Results of
      an online survey.
AB  - The aim of the present study was to measure the subjective well-being of a group
      of 225 UK registered mental health nurses (MHN) using three survey measures, and
      to identify whether certain demographic and workplace factors correlated with
      subjective well-being measure scores. An online survey incorporating the
      subjective well-being questions used by the Office for National Statistics, the
      Satisfaction with Life Scale, and the Warwick Edinburgh Mental Well-Being Scale
      was administered to members of two professional bodies for MHN. There was good
      consistency between the three subjective well-being measures, each demonstrating
      that UK MHN had a relatively low subjective well-being. Apart from the Office for
      National Statistics question, 'Overall, to what extent do you feel the things you
      do in your life are worthwhile?', demographic and workplace factors did not
      correlate with subjective well-being measure scores, although the characteristics
      of being male, living alone, and being aged 40-49 years were associated with
      lower mean scores on all three measures. The findings of the exploratory study
      suggest that a similar study should be undertaken with a larger representative
      population of MHN, and that qualitative research should explore why and how UK
      MHN have relatively low subjective well-being. The limitations of this study,
      namely the response rate and sample representativeness, mean that the results of
      the present study must be tested in further research on the MHN population.

PMID- 27878918
TI  - Survey of antipsychotic medication curriculum content in Australian university
      nursing programmes.
AB  - Antipsychotic medication has long been one of the first-line interventions for
      people with serious mental illness, with outcomes including reductions in
      symptoms and relapse rates. More recently, however, questions have been raised
      about the efficacy of antipsychotic medications, especially in light of their
      side-effect profile. Such questions have implications for the nurses
      administering antipsychotic medications, particularly in relation to their
      knowledge of the antipsychotic medication, its efficacy, and side-effect profile.
      Also important is the education of nursing students about antipsychotic
      medications, their use, and management. The present study reports findings of
      research that explored current curriculum content concerning
      psychopharmacological treatment in Australian undergraduate and postgraduate
      nursing programmes. Using a survey design, the research examined the content and
      modes of delivery of this content to gauge how well students are prepared for
      administering antipsychotic medication to people with serious mental illness.
      Findings of the research suggested the need for improvement in preparing nursing
      students to administer antipsychotic medication, including indications,
      contraindications, as well as recognition and management of side-effects.

PMID- 27878919
TI  - Effect of health status on fattening performance in young crossbred polish
      Holstein-Friesian * Limousin Bulls and steers.
AB  - The aim of this study was to determine the effect of disease incidence on
      selected parameters of cattle fattening performance and carcass quality, and the
      fatty acid profile of beef. The experimental materials comprised 16 bulls and 16
      steers, Polish Holstein-Friesian * Limousin crossbreeds (including 10 healthy and
      six treated animals of each category). At 5 weeks of age, bloodless castration
      was carried out using a rubber elastrator. The calves were fed milk replacer
      provided in automatic feeding stations. Until 540 days of age, the animals were
      fattened in an Animal Research Laboratory equipped with the Roughage Intake
      Control (RIC) system (Insentec, the Netherlands). In comparison with healthy
      (untreated) bulls and steers, sick (treated) animals had lower average body
      weight at 180 days of age, by 37 kg (P <= 0.05) and lower average final body
      weight at 540 days of age, by 56 kg (P <= 0.05). Sick animals were characterized
      by lower feed intake and worse feed efficiency (not statistically significant
      differences). Hot carcass weight reached 318 kg in healthy animals and 258 kg in
      treated bulls (P <= 0.05). In treated steers, the percentage of lean meat and
      bones in the three-rib section was higher and the percentage of fat was lower,
      compared with their healthy counterparts (P <= 0.01). There was a category *
      health status interaction for carcass tissue composition. There were no
      significant influences of type of sickness on analyzed traits. In comparison with
      healthy steers, intramuscular fat of Musculus longissimus dorsi (MLD) from
      treated steers had significantly (P <= 0.05) higher concentrations of
      polyunsaturated fatty acids (n-6 and n-3) and a lower content of conjugated
      linoleic acid.

PMID- 27878920
TI  - 'Framed': Terminating the Parenting Rights of Parents with Intellectual
      Disability in Iceland.
AB  - BACKGROUND: The aim was to investigate the role of measured intellectual function
      in framing parents as 'unfit' in child custody deprivation cases. METHOD:
      Grounded theory was used to analyse a national sample of custody deprivation
      cases in Iceland 2002-2014. RESULTS: The terminology used to evaluate and
      describe the intellectual and developmental status of parents in child
      deprivation custody cases served as a device to define and shape the 'unfit
      parent'. Intellect itself, whether as low, average or even above average at times
      acts as a master narrative which informs and explains all manner of perceived
      parental deficiencies. CONCLUSION: The intellectual and developmental status
      served as a yardstick of identifying, understanding and interpreting the unfit
      parent. As a tool to achieve an end, parents were framed in language and culture
      using underlying belief set to make sense of events and issues.

PMID- 27878921
TI  - Systematic review of reusable versus disposable laparoscopic instruments: costs
      and safety.
AB  - BACKGROUND: The quality of instruments and surgical expertise in minimally
      invasive surgery has developed markedly in the last two decades. Attention is now
      being turned to ways to allow surgeons to adopt more cost-effective and
      environmental-friendly approaches. This review explores current evidence on the
      cost and environmental impact of reusable versus single-use instruments. In
      addition, we aim to compare their quality, functionality and associated clinical
      outcomes. METHOD: The Medline and EMBASE databases were searched for relevant
      literature from January 2000 to May 2015. Subject headings were Equipment Reuse/,
      Disposable Equipment/, Cholecystectomy/, Laparoscopic/, Laparoscopy/, Surgical
      Instruments/, Medical Waste Disposal/, Waste Management/, Medical Waste/,
      Environmental Sustainability/ and Sterilization/. RESULTS: There are few
      objective comparative analyses between single-use versus reusable instruments.
      Current evidence suggests that limiting use of disposal instruments to necessity
      may hold both economical and environmental advantages. Theoretical advantages of
      single-use instruments in quality, safety, sterility, ease of use and importantly
      patient outcomes have rarely been examined. Cost-saving methods, environmental
      friendly methods, global operative costs, hidden costs, sterilization methods and
      quality assurance systems vary greatly between studies making it difficult to
      gain an overview of the comparison between single-use and reusable instruments.
      CONCLUSIONS: Further examination of cost comparisons between disposable and
      reusable instruments is necessary while externalized environmental costs,
      instrument function and safety are also important to consider in future studies.

PMID- 27878922
TI  - A NodD-like protein activates transcription of genes involved with naringenin
      degradation in a flavonoid-dependent manner in Herbaspirillum seropedicae.
AB  - Herbaspirillum seropedicae is an associative, endophytic non-nodulating
      diazotrophic bacterium that colonises several grasses. An ORF encoding a LysR
      type transcriptional regulator, very similar to NodD proteins of rhizobia, was
      identified in its genome. This nodD-like gene, named fdeR, is divergently
      transcribed from an operon encoding enzymes involved in flavonoid degradation
      (fde operon). Apigenin, chrysin, luteolin and naringenin strongly induce
      transcription of the fde operon, but not that of the fdeR, in an FdeR-dependent
      manner. The intergenic region between fdeR and fdeA contains several generic LysR
      consensus sequences (T-N11 -A) and we propose a binding site for FdeR, which is
      conserved in other bacteria. DNase I foot-printing revealed that the interaction
      with the FdeR binding site is modified by the four flavonoids that stimulate
      transcription of the fde operon. Moreover, FdeR binds naringenin and chrysin as
      shown by isothermal titration calorimetry. Interestingly, FdeR also binds in
      vitro to the nod-box from the nodABC operon of Rhizobium sp. NGR234 and is able
      to activate its transcription in vivo. These results show that FdeR exhibits two
      features of rhizobial NodD proteins: nod-box recognition and flavonoid-dependent
      transcription activation, but its role in H. seropedicae and related organisms
      seems to have evolved to control flavonoid metabolism.

PMID- 27878923
TI  - Prevalence, Trends and Custody Among Children of Parents with Intellectual
      Disabilities in Norway.
AB  - BACKGROUND: This study addresses children of parents with intellectual disability
      in Norway. The aim was to examine: (i) the impact of definitions of intellectual
      disability on prevalence, (ii) whether numbers were increasing, (iii) the
      prevalence of motherhood and fatherhood and (iv) rates of lost custody. METHODS:
      Analyses of national registers (n = 30 834) and mapping in four municipalities (n
      = 85). RESULTS: 0.19% of all children had parents with recorded intellectual
      disability, increasing to 0.87% with wider inclusion criteria. The number of
      children born to parents with intellectual disability has been declining since
      the mid-1980s. The proportion of mothers with intellectual disability was twice
      that of fathers. Parental custody was revoked for 30-50% of children, with single
      mothers being at particular risk. Parents with intellectual disability accounted
      for 20-25% of all custody cases. CONCLUSIONS: The results show that prevalence
      depends on the definition of intellectual disability. The decreasing number of
      children and the need for development of specially adapted family supports are
      discussed.

PMID- 27878924
TI  - Differences in rumen fermentation characteristics between low-yield and high
      yield dairy cows in early lactation.
AB  - Relationship between rumen fermentation parameters, blood biochemical profiles
      and milk production traits in different yielding dairy cows during early
      lactation was investigated. Twelve dairy cows were divided into two groups based
      on their milk yield, that is low-yield (LY) and high-yield (HY) groups. Rumen
      fluid and blood were collected at 3 weeks prepartum and 4, 8 and 12 weeks
      postpartum. Results showed that proportions of acetate, propionate to total short
      chain fatty acids and acetate : propionate ratio were changed (P < 0.05) in both
      groups during the peripartum period, whereas butyrate and acetate : butyrate
      ratio were only altered in the HY group. Blood cholesterol, beta-hydroxybutyric
      acid (BHBA) and glutamic oxaloacetic transaminase in the HY group were higher (P
      < 0.01) than those in the LY group. Principal component analysis revealed that
      milk yield and milk compositions were differently clustered between groups. These
      parameters showed similar direction with dry matter intake in the HY group and
      adverse direction in the LY group. Linear regression analysis indicated that
      butyrate was positively correlated with BHBA (P < 0.05) in the HY group. This
      study suggests that cows in the HY group seem to accommodate appropriately to
      negative energy balance in early lactation through rumen fermentation.

PMID- 27878926
TI  - The Effects of DWI-Infarct Lesion Volume on DWI-FLAIR Mismatch: Is There a Need
      for Size Stratification?
AB  - BACKGROUND: The lack of fluid-attenuated inversion-recovery (FLAIR)
      hyperintensity in areas of diffusion-weighted imaging (DWI) high signal, or DWI
      FLAIR mismatch, is a potential imaging biomarker for timing of stroke onset. We
      aimed to determine the effects of DWI infarct lesion volume on DWI-FLAIR mismatch
      and its accuracy for identification of strokes within intravenous (IV) the
      thrombolytic therapy window. METHODS: Acute ischemic stroke patients with
      magnetic resonance imaging scan within 12 hours of witnessed stroke were
      included. Two neuroradiologists independently reviewed DWI and FLAIR sequences
      for DWI-FLAIR mismatch in areas of restricted diffusion compared to the
      contralateral normal side. RESULTS: DWI-FLAIR mismatch was identified in 21/82
      (26%) patients. Infarct lesions with DWI-FLAIR mismatch were scanned earlier (3.8
      +/- .3 vs. 7.5 +/- .3 hours from onset, P < .001) and were smaller in size (8.9+/
      2.3 vs. 43.1+/-11.9 mL, P = .007) compared to lesions without mismatch.
      Multivariate regression analysis showed a significant interaction between lesion
      volume and time-from-onset in relationship with the presence of DWI-FLAIR
      mismatch (P = .045). The presence of DWI-FLAIR mismatch had 56% sensitivity, 83%
      specificity, 48% positive predictive value (PPV), and 87% negative predictive
      value (NPV) for identification of infarction within 4.5 hours of symptom onset;
      while for infarct lesions >15 mL, the DWI-FLAIR mismatch had 100% specificity and
      PPV for acute infarcts within 4.5 hours of onset. CONCLUSION: The effects of
      stroke onset-to-scan time gap on DWI-FLAIR mismatch are not the same for
      different DWI lesion volumes. At DWI lesion volumes >15 mL, the DWI-FLAIR
      mismatch is highly specific for acute infarcts within IV thrombolytic therapy
      time, and can identify wake-up stroke patients eligible for treatment.

PMID- 27878927
TI  - The septin protein Sep4 facilitates host infection by plant fungal pathogens via
      mediating initiation of infection structure formation.
AB  - Many phytopathogenic fungi use infection structures (IFSs, i.e., appressoria and
      infection cushions) to penetrate host cuticles. However, the conserved mechanisms
      that mediate initiation of IFS formation in divergent pathogens upon sensing the
      presence of host plants remain obscure. Here, we demonstrate that a conserved
      septin gene SEP4 plays crucial roles in this process. Disruption of SEP4 in the
      plant grey mould fungus Botrytis cinerea completely blocked IFS formation and
      abolished the virulence of DeltaBcsep4 mutants on unwounded hosts. During IFS
      formation, mutants lacking SEP4 could produce reactive oxygen species (ROS)
      normally. Inhibition of ROS production in strains harbouring the SEP4 gene
      resulted in disordered assembly of Sep4 and the subsequent failure to form
      infection cushions, suggesting that proper Sep4 assembly regulated by ROS is
      required for initiation of IFS formation and infection. Moreover, loss of SEP4
      severely impaired mutant conidiation, melanin and chitin accumulation in hyphal
      tips and lesion expansion on wounded hosts, but significantly promoted germ tube
      elongation and sclerotium production. SEP4-mediated fungal pathogenic
      development, including IFS formation, was validated in the hemibiotroph
      Magnaporthe oryzae. Our findings indicate that Sep4 plays pleiotropic roles in B.
      cinerea development and specifically facilities host infection by mediating
      initiation of IFS formation in divergent plant fungal pathogens in response to
      ROS signaling.

PMID- 27878925
TI  - Left ventricular deformation at rest predicts exercise-induced elevation in
      pulmonary artery wedge pressure in patients with unexplained dyspnoea.
AB  - AIMS: Impaired left ventricular (LV) deformation despite preserved LV ejection
      fraction (LVEF) is common and predicts outcomes in heart failure with preserved
      LVEF. We hypothesized that impaired LV deformation at rest is a marker of
      impaired cardiac systolic and diastolic reserve, and aimed to determine whether
      resting longitudinal (LS) and circumferential strain (CS) are associated with
      invasively measured haemodynamic response to exercise in patients with dyspnoea
      and a normal LVEF. METHODS AND RESULTS: We studied 85 patients with LVEF >=50%
      and free of significant valvular disease who were referred for evaluation of
      dyspnoea. All patients underwent rest echocardiography followed by right heart
      catheterization and cardiopulmonary exercise testing with concomitant invasive
      haemodynamic monitoring. The LS, CS and CS/LS ratio were measured by two
      dimensional speckle-tracking echocardiography at rest. Lower absolute LS at rest
      was associated with greater increase in pulmonary arterial wedge pressure (PAWP)
      from rest to peak exercise (r = 0.23, P = 0.034). In contrast, higher absolute CS
      at rest predicted a greater increase in PAWP (r = - 0.27, P = 0.032) and greater
      stroke volume augmentation with exercise (r = - 0.26, P = 0.021). Higher CS/LS
      ratio was most predictive of elevation in PAWP with exercise (r = 0.30, P =
      0.015). Of the measures of LV systolic and diastolic function assessed, the CS/LS
      ratio resulted in the highest area under the curve and specificity for the
      presence of rest- or exercise-induced pulmonary venous hypertension. CONCLUSION:
      Left ventricular deformation at rest predicts exercise-induced rise in PAWP among
      patients with dyspnoea and a preserved LVEF. A pattern of rest deformation
      characterized by worse LS and exaggerated CS is most strongly associated with
      exercise-induced rise in PAWP.

PMID- 27878928
TI  - Sentinel lymph node biopsy for early oral cancers: Westmead Hospital experience.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) has become an alternative option to
      elective neck dissection (END) for early oral cavity squamous cell carcinoma
      (OCSCC) outside of Australia. We sought to assess the technical feasibility of
      SLNB and validate its accuracy against that of END in an Australian setting.
      METHODS: We performed a prospective cohort study consisting of 30 consecutive
      patients with cT1-2 N0 OCSCC referred to the Head and Neck Cancer Service,
      Westmead Hospital, Sydney, between 2011 and 2014. All patients underwent SLNB
      followed by immediate selective neck dissection (levels I-III). RESULTS: A total
      of 30 patients were diagnosed with an early clinically node-negative OCSCC (seven
      cT1 and 23 cT2), with the majority located on the oral tongue. A median of three
      (range: 1-14) sentinel nodes were identified on lymphoscintigraphy, and all
      sentinel nodes were successfully retrieved, with 50% having a pathologically
      positive sentinel node. No false-negative sentinel nodes were identified using
      selective neck dissection as the gold standard. The negative predictive value
      (NPV) of SLNB was 100%, with 40% having a sentinel node identified outside the
      field of planned neck dissection on lymphoscintigraphy. Of these, one patient had
      a positive sentinel node outside of the ipsilateral supraomohyoid neck dissection
      template. CONCLUSION: SLNB for early OCSCC is technically feasible in an
      Australian setting. It has a high NPV and can potentially identify at-risk
      lymphatic basins outside the traditional selective neck dissection levels even in
      well-lateralized lesions.

PMID- 27878929
TI  - Ambulatory glucose profile analysis of the juvenile diabetes research foundation
      continuous glucose monitoring dataset-Applications to the pediatric diabetes
      population.
AB  - BACKGROUND: Increased continuous glucose monitor (CGM) use presents both the
      benefit and burden of increased data for clinicians to rapidly analyze. The
      ambulatory glucose profile (AGP) is an evolving a universal software report for
      CGM data analysis. OBJECTIVES/HYPOTHESES: We utilized the Juvenile Diabetes
      Research Foundation-CGM dataset to evaluate the AGP across a broad spectrum of
      patients to show how AGP can be used clinically to assist with CGM-related
      decision making. We hypothesized that AGP metrics would be different across age
      and HbA1c strata. SUBJECTS: AGPs were generated from the JDRF-CGM trial dataset
      for all periods during which there were >=10 days of CGM coverage in the 2 weeks
      adjacent to an HbA1c measurement yielding 1101 AGPs for 393 unique subjects.
      METHODS: AGPs were stratified by age group (8-14, 15-24, and >=25 years) and
      HbA1c (within or above target for age) and compared for between group differences
      in AGP metrics via two-factor ANOVA. Glycemic differences between time periods
      were analyzed via segmented regression analysis. RESULTS: Glucose exposure
      (average and estimated A1c) and variability (standard deviation and interquartile
      range) were different between the low and high HbA1c levels. Within a given HbA1c
      level all age groups were significantly different from each other with older
      patients having lower averages with less variability than younger patients.
      CONCLUSIONS: AGP analysis of the JDRF-CGM data highlights significant differences
      in glycemic profiles between pediatric and adult age groups and between well and
      less well-controlled patient populations.

PMID- 27878930
TI  - Good Enough Support? Exploring the Attitudes, Knowledge and Experiences of
      Practitioners in Social Services and Child Welfare Working with Mothers with
      Intellectual Disability.
AB  - BACKGROUND: This study examined the attitudes, knowledge and experiences of
      practitioners in social services and child welfare working with mothers with
      intellectual disability. METHOD: The authors used a national survey, which was
      completed by 329 participants. Descriptive statistics and frequency tables were
      generated, and the associations between variables and differences between various
      subgroups of the sample were made. The open questions were analysed using the
      processes involved in content analysis. RESULTS: The findings indicated that the
      participants had limited knowledge of available supports and services for mothers
      with intellectual disability. Furthermore, many participants believed that
      mothers with intellectual disability should have an abortion should they become
      pregnant. The findings show practitioners' stereotyped attitudes towards mothers
      with intellectual disability. CONCLUSIONS: Workers in the area of social services
      and child welfare need access to training and professional development in the
      area of supporting mothers with intellectual disability.

PMID- 27878932
TI  - Glycerol metabolism and transport in yeast and fungi: established knowledge and
      ambiguities.
AB  - There is huge variability among yeasts with regard to their efficiency in
      utilizing glycerol as the sole source of carbon and energy. Certain species show
      growth rates with glycerol comparable to those reached with glucose as carbon
      source; others are virtually unable to utilize glycerol, especially in synthetic
      medium. Most of our current knowledge regarding glycerol uptake and catabolic
      pathways has been gained from studying laboratory strains of the model yeast
      Saccharomyces cerevisiae. The growth of these strains on glycerol is dependent on
      the presence of medium supplements such as amino acids and nucleobases. In
      contrast, there is only fragmentary knowledge about S. cerevisiae isolates able
      to grow in synthetic glycerol medium without such supplements as well as about
      growth of non-Saccharomyces yeast species on glycerol. Thus, more research is
      required to understand why certain strains and species show superior growth
      performance on glycerol compared with common S. cerevisiae laboratory strains.
      This mini-review summarizes what is known so far about the gene products and
      pathways involved in glycerol metabolism and transport in yeast and fungi as well
      as the regulation of these processes.

PMID- 27878933
TI  - Psychiatric disorders during early adulthood in those with childhood onset type 1
      diabetes: Rates and clinical risk factors from population-based follow-up.
AB  - AIM: To determine the incidence of and risk factors for psychiatric disorders in
      early adulthood in patients with childhood onset type 1 diabetes (T1D). METHODS:
      In this retrospective-cohort study, we identified a population-based childhood
      onset T1D cohort and an age and sex matched (5:1) non-diabetic comparison cohort.
      Data linkage was used to access inpatient hospitalization data, mental health
      support service data, and mortality data to follow-up both cohorts into early
      adulthood. RESULTS: The mean age of T1D diagnosis was 9.5 years (SD 4.1), with a
      mean age at end of follow-up of 26.4 years (SD 5.2, max 37.7). The diagnosis of
      any psychiatric disorder was observed for 187 of 1302 (14.3%) in the T1D cohort
      and 400 of 6422 (6.2%) in the comparison cohort [adjusted hazard ratio (HR) 2.3;
      95% CI 1.9, 2.7]. Anxiety, eating, mood, and personality and behaviour disorders
      were observed at higher rates within the T1D cohort. Comorbid psychiatric
      disorders were more frequent, at the cohort level, within the T1D cohort (2-3
      disorders 3.76% vs 1.56%) and service utilization was higher (15+ contacts 6.8%
      vs 2.8%); though these differences did not remain when restricted to only those
      individuals diagnosed during follow-up. A history of poor glycaemic control was
      associated with an increased risk of anxiety, mood, and 'any' disorder (HR
      ranging from 1.35 to 1.42 for each 1% increase in mean paediatric HbA1c).
      CONCLUSION: Our findings highlight the need for access to mental health support
      services as part of routine patient care for young adults with T1D, and for
      better predictive tools to facilitate targeting at-risk patients with early
      intervention programs.

PMID- 27878934
TI  - Two degradation strategies for overcoming the recalcitrance of natural
      lignocellulosic xylan by polysaccharides-binding GH10 and GH11 xylanases of
      filamentous fungi.
AB  - The recalcitrance of lignocellulose forms a strong barrier for the bioconversion
      of lignocellulosic biomass in chemical or biofuel industries. Filamentous fungi
      are major plant biomass decomposer, and capable of forming all the required
      enzymes. Here, they characterized the GH10 and GH11 endo-xylanases and a CE1
      acetyl-xylan esterase (Axe1) from a superior biomass-degrading strain,
      Aspergillus fumigatus Z5, and examined how they interact in xylan degradation.
      Cellulose-binding (CBM1) domain inhibited GH10 xylanase activities for pure
      xylan, but afforded them an ability to hydrolyze washed corncob particles (WCCP).
      CBM1-containing GH10 xylanases also showed synergism with CBM1-containing Axe1 in
      WCCP hydrolysis, and this synergy was strictly dependent on the presence of their
      CBM1 domains. In contrast, GH11 xylanases had no CBM1, but still could bind xylan
      and hydrolyzed WCCP; however, no synergism displayed with Axe1. GH10 xylanases
      and GH11 xylanases showed a pronounced synergism in WCCP hydrolysis, which was
      dependent on the presence of the CBM1 in GH10 xylanases and absence from GH11
      xylanases. They exhibit different mechanisms to bind to cellulose and xylan, and
      act in synergy when these two structures are intact. These findings will be
      helpful for the further development of highly efficient enzyme mixtures for
      lignocellulosic biomass conversion.

PMID- 27878935
TI  - Public and patient involvement in health policy: A continuously growing field.

PMID- 27878936
TI  - Citizens' preferences on healthcare expenditure allocation: evidence from Greece.
AB  - BACKGROUND OF CONTEXT: Priority setting and resource allocation across various
      healthcare functions are critical issues in health policy and strategic decision
      making. As health resources are limited while there are so many health challenges
      to resolve, consumers and payers have to make difficult decisions about
      expenditure allocation. OBJECTIVE: Our research focus on the (dis)agreement
      between citizens' preferences and actual public health expenditure across broad
      healthcare functions, on whether this (dis)agreement is persistent, on whether
      various demographic factors amplify this (dis)agreement and to derive useful
      implications for public health policies. SETTING AND PARTICIPANTS: Using survey
      data of 3029 citizens in Greece for the year 2012 and employing logit estimation
      techniques, we analysed the effect of demographic and other factors in shaping
      citizens' (dis)agreement with public health expenditure allocation. RESULTS: Our
      results demonstrate the important role of income, family members and residence in
      shaping citizens' preferences regarding health expenditure priorities in almost
      all healthcare functions, while other demographic factors such as job, age,
      gender and marital status do partly associate and play a significant role.
      CONCLUSIONS: Government should encourage the citizens' participation in the
      decision-making process in order to eliminate the unveiled and significant
      disagreement between citizens' preferences and actual public health expenditure
      across all healthcare functions.

PMID- 27878938
TI  - The Impact of Affiliate Stigma on the Psychological Well-Being of Mothers of
      Children with Specific Learning Disabilities in India: The Mediating Role of
      Subjective Burden.
AB  - BACKGROUND: Knowledge of the impact of affiliate stigma on the wellbeing of
      caregivers to children with specific learning disability (SLD) in India is
      limited. To fill in this gap in knowledge a cross-sectional quantitative study
      was undertaken to assess the impact of affiliate stigma on the psychological well
      being of mothers with children with SLD in India, and test the mediating role of
      subjective burden, using an adapted version of Pearlin's stress and adaptation
      model. METHODS: Sample included 100 mothers of children with SLD. Data was
      collected using a structured interview schedule. Descriptive statistics,
      correlation and stepwise regression were used as the primary analytic tools.
      RESULTS: Affiliate stigma experienced by mothers significantly predicted low
      levels of psychological well-being and subjective burden mediated the
      relationship between affiliate stigma and psychological wellbeing. CONCLUSIONS:
      The findings call for developing targeted interventions to address affiliate
      stigma and positive appraisal of the caregiving situation, with the goal of
      improving the psychological well-being of mothers of children with SLD.

PMID- 27878940
TI  - People, processes, and systems: An observational study of the role of technology
      in rural youth mental health services.
AB  - The merits of technology-based mental health service reform have been widely
      debated among academics, practitioners, and policy makers. The design of new
      technologies must first be predicated on a detailed appreciation of how the
      mental health system works before it can be improved or changed through the
      introduction of new products and services. Further work is required to better
      understand the nature of face-to-face mental health work and to translate this
      knowledge to computer scientists and system designers responsible for creating
      technology-based solutions. Intensive observation of day-to-day work within two
      rural youth mental health services in South Australia, Australia, was undertaken
      to understand how technology could be designed and implemented to enhance young
      people's engagement with services and improve their experience of help seeking.
      Data were analysed through a lens of complexity theory. Results highlight the
      variety of professional roles and services that can comprise the mental health
      system. The level of interconnectedness evident in the system contrasted with
      high levels of service self-organization and disjointed information flow. A
      mental health professional's work was guided by two main constructs: risk and
      engagement. Most clients presented with a profile of disability, disadvantage,
      and isolation, so complex client presentations and decision-making were core
      practices. Clients (and frequently, their families) engaged with services in a
      crisis-dependent manner, characterized by multiple disengagements and re
      engagements over time. While significant opportunities exist to integrate
      technology into existing youth mental health services, technologies for this
      space must be usable for a broad range of medical, psychological and cognitive
      disability, social disadvantage, and accommodate repeat cycles of
      engagement/disengagement over time.

PMID- 27878941
TI  - The Social-Emotional Well-Being of Children of Mothers with Intellectual
      Impairment: A Population-Based Analysis.
AB  - BACKGROUND: Children of parents with intellectual impairment are thought to be at
      risk for poor social-emotional well-being. This study investigated the
      relationship between maternal intellectual impairment and poor child social
      emotional well-being. METHOD: Secondary analysis of data from waves 2-4 of the
      Millennium Cohort Study (UK). Social-emotional well-being was measured by
      maternal report at Waves 2-4, with teacher and child self-report at Wave 4.
      Bivariate and multivariate analyses were conducted. RESULTS: Unadjusted, maternal
      intellectual impairment was associated with an elevated risk of overall poor
      social-emotional well-being at ages 3 and 5, but not at age 7. After controlling
      for individual, family and environmental characteristics, no statistically
      significant association was found between maternal intellectual impairment and
      poor child social-emotional well-being. CONCLUSIONS: Children of mothers with
      intellectual impairment are more likely than their peers to be exposed to adverse
      living conditions. These living conditions may explain, at least in part, why
      these children face a heightened risk of poor social-emotional well-being at ages
      3 and 5. Improving the living conditions of mothers with intellectual impairment
      may offer a pathway to child social-emotional well-being.

PMID- 27878939
TI  - Botulinum toxin A for palmar hyperhidrosis: assessment with sympathetic skin
      responses evoked by train of stimuli.
AB  - Objective assessment of the effect of botulinum toxin A (BT) treatment in primary
      palmar hyperhidrosis (PH) is attempted by different methods. We decided to use
      for this purpose sympathetic skin responses evoked by train of stimuli (TSSR).
      Twenty patients with severe PH (five female, median age 24, range 18-36) were
      examined regularly over 3 months after receiving 50 UI BT in each palm. TSSR were
      recorded from the palms after sensory stimulation by a train of three
      supramaximal electric pulses 3 millisecond apart. Results were compared to
      longitudinally studied TSSR of 20 healthy sex- and age-matched control subjects.
      All hyperhidrosis patients reported excellent improvement. TSSR amplitudes
      decreased at week 1 (mean 54% range 48%-67%) and over the following months in a
      clinically significant trend (slope R=-.82, P<.0001). TSSR in controls changed
      insignificantly (+/-13% from the baseline). The difference between patients and
      controls was highly significant at any time point (P<.001). This study suggests
      that TSSR may help in assessment of treatments in PH. It confirms objectively the
      efficacy of BT in PH.

PMID- 27878937
TI  - Patient and family involvement in adult critical and intensive care settings: a
      scoping review.
AB  - BACKGROUND: Despite international bodies calling for increased patient and family
      involvement, these concepts remain poorly defined within literature on critical
      and intensive care settings. OBJECTIVE: This scoping review investigates the
      extent and range of literature on patient and family involvement in critical and
      intensive care settings. Methodological and empirical gaps are identified, and a
      future agenda for research into optimizing patient and family involvement is
      outlined. METHODS: Searches of MEDLINE, CINAHL, Social Work Abstracts and
      PsycINFO were conducted. English-language articles published between 2003 and
      2014 were retrieved. Articles were included if the studies were undertaken in an
      intensive care or critical care setting, addressed the topic of patient and
      family involvement, included a sample of adult critical care patients, their
      families and/or critical care providers. Two reviewers extracted and charted data
      and analysed findings using qualitative content analysis. FINDINGS: A total of
      892 articles were screened, 124 were eligible for analysis, including 61
      quantitative, 61 qualitative and 2 mixed-methods studies. There was a significant
      gap in research on patient involvement in the intensive care unit. The analysis
      identified five different components of family and patient involvement: (i)
      presence, (ii) having needs met/being supported, (iii) communication, (iv)
      decision making and (v) contributing to care. CONCLUSION: Three research gaps
      were identified that require addressing: (i) the scope, extent and nature of
      patient involvement in intensive care settings; (ii) the broader socio-cultural
      processes that shape patient and family involvement; and (iii) the bidirectional
      implications between patient/family involvement and interprofessional teamwork.

PMID- 27878942
TI  - Morphological evolution of the mammalian jaw adductor complex.
AB  - The evolution of the mammalian jaw during the transition from non-mammalian
      synapsids to crown mammals is a key event in vertebrate history and characterised
      by the gradual reduction of its individual bones into a single element and the
      concomitant transformation of the jaw joint and its incorporation into the middle
      ear complex. This osteological transformation is accompanied by a rearrangement
      and modification of the jaw adductor musculature, which is thought to have
      allowed the evolution of a more-efficient masticatory system in comparison to the
      plesiomorphic synapsid condition. While osteological characters relating to this
      transition are well documented in the fossil record, the exact arrangement and
      modifications of the individual adductor muscles during the cynodont-mammaliaform
      transition have been debated for nearly a century. We review the existing
      knowledge about the musculoskeletal evolution of the mammalian jaw adductor
      complex and evaluate previous hypotheses in the light of recently documented
      fossils that represent new specimens of existing species, which are of central
      importance to the mammalian origins debate. By employing computed tomography (CT)
      and digital reconstruction techniques to create three-dimensional models of the
      jaw adductor musculature in a number of representative non-mammalian cynodonts
      and mammaliaforms, we provide an updated perspective on mammalian jaw muscle
      evolution. As an emerging consensus, current evidence suggests that the mammal
      like division of the jaw adductor musculature (into deep and superficial
      components of the m. masseter, the m. temporalis and the m. pterygoideus) was
      completed in Eucynodontia. The arrangement of the jaw adductor musculature in a
      mammalian fashion, with the m. pterygoideus group inserting on the dentary was
      completed in basal Mammaliaformes as suggested by the muscle reconstruction of
      Morganucodon oehleri. Consequently, transformation of the jaw adductor
      musculature from the ancestral ('reptilian') to the mammalian condition must have
      preceded the emergence of Mammalia and the full formation of the mammalian jaw
      joint. This suggests that the modification of the jaw adductor system played a
      pivotal role in the functional morphology and biomechanical stability of the jaw
      joint.

PMID- 27878943
TI  - Microbial community composition but not diversity changes along succession in
      arctic sand dunes.
AB  - The generality of increasing diversity of fungi and bacteria across arctic sand
      dune succession was tested. Microbial communities were examined by high
      throughput sequencing of 16S rRNA genes (bacteria) and internal transcribed
      spacer (ITS) regions (fungi). We studied four microbial compartments (inside
      leaf, inside root, rhizosphere and bulk soil) and characterized microbes
      associated with a single plant species (Deschampsia flexuosa) across two sand
      dune successional stages (early and late). Bacterial richness increased across
      succession in bulk soil and leaf endosphere. In contrast, soil fungal richness
      remained constant while root endosphere fungal richness increased across
      succession. There was, however, no significant difference in Shannon diversity
      indices between early and late successional stage in any compartment. There was a
      significant difference in the composition of microbial communities between early
      and late successional stage in all compartments, although the major microbial
      OTUs were shared between early and late successional stage. Co-occurrence network
      analysis revealed successional stage-specific microbial groups. There were more
      co-occurring modules in early successional stage than in late stage. Altogether,
      these results emphasize that succession strongly affects distribution of
      microbial species, but not microbial diversity in arctic sand dune ecosystem and
      that fungi and bacteria may not follow the same successional trajectories.

PMID- 27878946
TI  - Targeted inhibition of Polo-like kinase 1 by a novel small-molecule inhibitor
      induces mitotic catastrophe and apoptosis in human bladder cancer cells.
AB  - Bladder cancer is a common cancer with particularly high recurrence after
      transurethral resection. Despite improvements in neoadjuvant chemotherapy, the
      outcome of patients with advanced bladder cancer has changed very little. In this
      study, the anti-tumour activities of a novel Polo-like kinase 1 (PLK1) inhibitor
      (RO3280) was evaluated in vitro and in vivo in the bladder carcinoma cell lines
      5637 and T24. MTT assays, colony-formation assays, flow cytometry, cell
      morphological analysis and trypan blue exclusion assays were used to examine the
      proliferation, cell cycle distribution and apoptosis of bladder carcinoma cells
      with or without RO3280 treatment. Moreover, real-time RT-PCR and Western blotting
      were used to detect the expressions of genes that are related to these cellular
      processes. Our results showed that RO3280 inhibited cell growth and cell cycle
      progression, increased Wee1 expression and cell division cycle protein 2
      phosphorylation. In addition, RO3280 induced mitotic catastrophe and apoptosis,
      increased cleaved PARP (poly ADP-ribose polymerase) and caspase-3, and decreased
      BubR1 expression. The in vivo assay revealed that RO3280 retarded bladder cancer
      xenograft growth in a nude mouse model. Although further laboratory and pre
      clinical investigations are needed to corroborate these data, our demonstration
      of bladder cancer growth inhibition and dissemination using a pharmacological
      inhibitor of PLK1 provides new opportunities for future therapeutic intervention.

PMID- 27878948
TI  - Core outcomes for studies of pregnancy with epilepsy.

PMID- 27878947
TI  - All together now: experimental multispecies biofilm model systems.
AB  - Studies of microorganisms have traditionally focused on single species
      populations, which have greatly facilitated our understanding of the genetics and
      physiology that underpin microbial growth, adaptation and biofilm development.
      However, given that most microorganisms exist as multispecies consortia, the
      field is increasingly exploring microbial communities using a range of
      technologies traditionally limited to populations, including meta-omics based
      approaches and high resolution imaging. The experimental communities currently
      being explored range from relatively low diversity, for example, two to four
      species, to significantly more complex systems, comprised of several hundred
      species. Results from both defined and undefined communities have revealed a
      number of emergent properties, including improved stress tolerance, increased
      biomass production, community level signalling and metabolic cooperation. Based
      on results published to date, we submit that community-based studies are timely
      and increasingly reveal new properties associated with multispecies consortia
      that could not be predicted by studies of the individual component species. Here,
      we review a range of defined and undefined experimental systems used to study
      microbial community interactions.

PMID- 27878944
TI  - The roles of bone-derived exosomes and exosomal microRNAs in regulating bone
      remodelling.
AB  - Pathological destructive bone diseases are primarily caused by the failure of a
      lifelong self-renewal process of the skeletal system called bone remodelling. The
      mechanisms underlying this process include enhanced osteoclast activity and
      decreased generation of the osteoblast lineage. Intercellular interaction and
      crosstalk among these cell types are crucial for the maintenance of bone
      remodelling, either through the secretion of growth factors or direct cell-cell
      physical engagement. Recent studies have revealed that exosomes derived from bone
      cells, including osteoclasts, osteoblasts and their precursors, play pivotal
      roles on bone remodelling by transferring biologically active molecules to target
      cells, especially in the processes of osteoclast and osteoblast differentiation.
      Here, we review the contents of bone-derived exosomes and their functions in the
      regulatory processes of differentiation and communication of osteoclasts and
      osteoblasts. In addition, we highlight the characteristics of microRNAs of bone
      derived exosomes involved in the regulation of bone remodelling, as well as the
      potential clinical applications of bone-derived exosomes in bone remodelling
      disorders.

PMID- 27878945
TI  - Regulatory non-coding RNAs in acute myocardial infarction.
AB  - Acute myocardial infarction (AMI) is one of the most common cardiovascular
      diseases that leads to high mortality and morbidity globally. Various therapeutic
      targets for AMI have been investigated in recent years, including the non-coding
      RNAs (ncRNAs). NcRNAs, a class of RNA molecules that typically do not code
      proteins, are divided into several subgroups. Among them, microRNAs (miRNAs) are
      widely studied for their modulation of several pathological aspects of AMI,
      including cardiomyocyte apoptosis, inflammation, angiogenesis and fibrosis. It
      has emerged that long ncRNAs (lncRNAs) and circular RNAs (circRNAs) also regulate
      these processes via interesting mechanisms. However, the regulatory functions of
      ncRNAs in AMI and their underlying functional mechanisms have not been
      systematically described. In this review, we summarize the recent findings
      involving ncRNA actions in AMI and briefly describe the novel mechanisms of these
      ncRNAs, highlighting their potential application as therapeutic targets in AMI.

PMID- 27878949
TI  - Dialytic hemodynamics are associated with changes in gait speed.
AB  - INTRODUCTION: Functional impairment and reduced mobility are prevalent in
      patients on chronic hemodialysis (HD). The impact of HD on physical performance
      and mobility needs evaluation. METHODS: We measured gait speed in a cohort of
      chronic HD patients both pre and post an HD session. We collected demographic and
      laboratory data and dialytic hemodynamic parameters for the HD session.
      Participants completed the Falls Efficacy Scale International (FES-I) survey to
      assess concern for falling. We used linear regression analysis to tests for
      associations between our predictor variables of intra-dialytic hemodynamic change
      and change in gait speed from pre to post HD (primary outcome) and FES-I score
      (secondary outcome). FINDINGS: Twenty-eight participants completed the study. The
      mean (SD) age was 64.0 (10.5) years. The majority were male (71.4%), had
      hypertension (85.7%) and diabetes (57.1%). The mean (SD) change in gait speed
      from pre to post dialysis was -0.06 (0.08) m/s. A greater decrease in gait speed
      was associated with greater decrease in SBP and DBP from pre to post HD (p = 0.02
      and p = 0.04, respectively) and greater maximum drop in SBP and DBP during HD (p
      = 0.01 and p <0.01, respectively). The association between maximum drop in SBP
      and DBP and gait speed remained significant after adjustment for covariates.
      There was no association between BP change and FES-I score. DISCUSSION: Our
      results suggest that HD patients who have greater decrease in BP during HD are at
      risk for decreased gait speed post HD.

PMID- 27878950
TI  - Comparison of the chemical profiles of fresh-raw and dry-processed Juglans
      mandshurica.
AB  - The processing of Juglans mandshurica Maxim. is important to reduce its toxicity
      and enhance its efficacy. Simple, efficient, and sensitive ultra-high performance
      liquid chromatography coupled with a time-of-flight mass spectrometry based
      chemical profiling approach was proposed to rapidly evaluate the chemical
      difference between fresh and dry samples. Under the optimized ultra-high
      performance liquid chromatography and quadrupole time-of-flight tandem mass
      spectrometry conditions, 81 significantly different compounds were rapidly
      discovered using principal component analysis, and then tentatively identified by
      comparison with reference substances or inferred through mass spectral fragment
      ion analysis and literature data. These compounds included 35 naphthoquinones, 11
      diarylheptanoids, nine flavonoids, eight triterpenes, 12 phenolic acids, and six
      aliphatics. The results demonstrated that chemical reactions occurring during
      processing could be used to elucidate the processing mechanism of Juglans
      mandshurica Maxim. This study provides a novel approach to identifying
      complicated components of various complex mixtures in fresh-raw and dry-processed
      traditional Chinese medicines, which could be used as a valid analytical method
      to further understand the processing mechanisms of these medicines, as well as
      providing intrinsic quality control of the medicines and their processed
      products.

PMID- 27878951
TI  - Alleviating Parenting Stress in Parents with Intellectual Disabilities: A
      Randomized Controlled Trial of a Video-feedback Intervention to Promote Positive
      Parenting.
AB  - BACKGROUND: Adapted parenting support may alleviate the high levels of parenting
      stress experienced by many parents with intellectual disabilities. METHODS:
      Parents with mild intellectual disabilities or borderline intellectual
      functioning were randomized to experimental (n = 43) and control (n = 42)
      conditions. Parents in both groups received care-as-usual. The experimental group
      also received an adapted version of video-feedback intervention for positive
      parenting and learning difficulties (VIPP-LD). Measures of parenting stress were
      obtained pre-test, post-test and 3-month follow-up. RESULTS: Randomization to the
      experimental group led to a steeper decline in parenting stress related to the
      child compared to the control group (d = 0.46). No statistically significant
      effect on stress related to the parent's own functioning or situation was found.
      CONCLUSIONS: The results of the study suggest the feasibility of reducing
      parenting stress in parents with mild intellectual disability (MID) through
      parenting support, to the possible benefit of their children.

PMID- 27878952
TI  - Newly isolated Nodularia phage influences cyanobacterial community dynamics.
AB  - Cyanophages, that is, viruses infecting cyanobacteria, are a key component
      driving cyanobacterial community dynamics both ecologically and evolutionarily.
      In addition to reducing biomass and influencing the genetic diversity of their
      host populations, they can also have a wider community-level impact due to the
      release of nutrients by phage-induced cell lysis. In this study, we isolated and
      characterized a new cyanophage, a siphophage designated as vB_NpeS-2AV2, capable
      of infecting the filamentous nitrogen fixing cyanobacterium Nodularia sp. AV2
      with a lytic cycle between 12 and 18 hours. The role of the phage in the ecology
      of its host Nodularia and competitor Synechococcus was investigated in a set of
      microcosm experiments. Initially, phage-induced cell lysis decreased the number
      of Nodularia cells in the cultures. However, around 18%-27% of the population was
      resistant against the phage infection. Nitrogen was released from the Nodularia
      cells as a consequence of phage activity, resulting in a seven-fold increase in
      Synechococcus cell density. In conclusion, the presence of the cyanophage vB_NpeS
      2AV2 altered the ecological dynamics in the cyanobacterial community and induced
      evolutionary changes in the Nodularia population, causing the evolution from a
      population dominated by susceptible cells to a population dominated by resistant
      ones.

PMID- 27878953
TI  - Long non-coding RNA linc00261 suppresses gastric cancer progression via promoting
      Slug degradation.
AB  - Gastric cancer (GC) remains a threat to public health with high incidence and
      mortality worldwide. Increasing evidence demonstrates that long non-coding RNAs
      (lncRNAs) play critical regulatory roles in cancer biology, including GC.
      Previous profiling study showed that lncRNA linc00261 was aberrantly expressed in
      GC. However, the role of linc00261 in GC progression and the precise molecular
      mechanism remain unknown. In this study, we report that linc00261 was
      significantly down-regulated in GC tissues and the expression level of linc00261
      negatively correlated with advanced tumour status and clinical stage as well as
      poor prognostic outcome. In vitro functional assays indicate that ectopic
      expression of linc00261 suppressed cell invasion by inhibiting the epithelial
      mesenchymal transition (EMT). By RNA pull-down and mass spectrum experiments, we
      identified Slug as an RNA-binding protein that binds to linc00261. We confirmed
      that linc00261 down-regulated Slug by decreasing the stability of Slug proteins
      and that the tumour-suppressive function of linc00261 can be neutralized by Slug.
      linc00261 may promote the degradation of Slug via enhancing the interaction
      between GSK3beta and Slug. Moreover, linc00216 overexpression repressed lung
      metastasis in vivo. Together, our findings suggest that linc00261 acts a tumour
      suppressor in GC by decreasing the stability of Slug proteins and suppressing
      EMT. By clarifying the mechanisms underlying GC progression, these findings may
      facilitate the development of novel therapeutic strategies for GC.

PMID- 27878955
TI  - Primary aldosteronism: from case detection to histopathology with up to 6 years
      of follow-up.
AB  - The authors aimed to investigate the clinical characteristics, accuracy of
      diagnostic tests, and long-term outcomes after interventions in patients
      diagnosed with primary aldosteronism (PA) in Iceland throughout 5 years. A
      retrospective chart review was performed for all patients diagnosed with PA
      during the years 2007-2011 at Landspitali Hospital in Iceland, a referral center
      for the whole country. Workup after detection included salt loading test,
      positional test, computed tomography, and adrenal vein sampling. Patients with
      unilateral disease were offered treatment with adrenalectomy. A total of 33
      patients were diagnosed with PA during the study period: 17 patients with
      bilateral disease and 16 with unilateral disease. Results from salt loading test
      were positive in 90% of patients. In patients with adenoma, 36% were responsive
      on their positional test and computed tomography scan showed a nodule in 73%. All
      patients with unilateral disease had a lateralization index >=3. After surgery,
      patients had lower systolic blood pressure (P<.001) and number of hypertensive
      medications (P<.01).

PMID- 27878956
TI  - Improving the medical school-residency transition.
AB  - BACKGROUND: In response to calls to improve the continuum between undergraduate
      and graduate medical education, many medical schools are creating electives
      designed to prepare students for residency training. There is a need for data
      that link improvements from these residency preparation courses to residency
      itself. Data is needed that links improvements from these residency preparation
      courses to residency OBJECTIVE: To examine senior medical student performance on
      the Association of Professors of Gynecology and Obstetrics (APGO) Preparation for
      Residency Knowledge Assessment before and after an obstetrics and gynaecology
      residency preparation elective, and to determine whether the knowledge
      improvements persisted to the start of the residency. METHODS: All 13 students
      enrolled in the course completed the APGO knowledge assessment on the first and
      last day of the elective. Three months later, the students were asked to re-take
      the assessment immediately prior to the start of their residency. RESULTS: There
      was improvement in mean scores from the pre-test score of 66.4 per cent to the
      post-test score of 77.4 per cent. At the time of the pre-test, three of the 13
      students (23%) had passing scores (70% or greater), and at the time of the post
      test, 11 of the 13 (85%) had passing scores. Nine of the 13 students (69%)
      completed the APGO knowledge assessment immediately prior to the start of their
      residency. Those nine students had a mean pre-residency score of 76.4 per cent.
      Eight of the nine students (89%) passed the pre-residency test. CONCLUSIONS: Our
      data support the value of residency preparation electives for improving
      knowledge, and suggest that senior medical school electives can help to bridge
      the continuum between undergraduate and graduate medical education.

PMID- 27878957
TI  - The mental health tribunal: a missed opportunity?

PMID- 27878954
TI  - Biomarkers of systemic lupus erythematosus identified using mass spectrometry
      based proteomics: a systematic review.
AB  - Advances in mass spectrometry technologies have created new opportunities for
      discovering novel protein biomarkers in systemic lupus erythematosus (SLE). We
      performed a systematic review of published reports on proteomic biomarkers
      identified in SLE patients using mass spectrometry-based proteomics and highlight
      their potential disease association and clinical utility. Two electronic
      databases, MEDLINE and EMBASE, were systematically searched up to July 2015. The
      methodological quality of studies included in the review was performed according
      to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
      Twenty-five studies were included in the review, identifying 241 SLE candidate
      proteomic biomarkers related to various aspects of the disease including disease
      diagnosis and activity or pinpointing specific organ involvement. Furthermore, 13
      of the 25 studies validated their results for a selected number of biomarkers in
      an independent cohort, resulting in the validation of 28 candidate biomarkers. It
      is noteworthy that 11 candidate biomarkers were identified in more than one
      study. A significant number of potential proteomic biomarkers that are related to
      a number of aspects of SLE have been identified using mass spectrometry proteomic
      approaches. However, further studies are required to assess the utility of these
      biomarkers in routine clinical practice.

PMID- 27878959
TI  - Students today...educators tomorrow.
AB  - BACKGROUND: The article describes the use of the mini clinical examination (mini
      CEX) in a pilot study to introduce peer assessment in one allied health programme
      to explore students' capacity as clinical educators. Preparing today's pre
      professional health students to be clinical educators by engaging them in peer
      teaching, learning and assessment may encourage them to become tomorrow's
      clinical educators. CONTEXT: Peer assessment is common among many undergraduate
      medical and allied health programmes, and is typically used as a means of
      providing students with feedback on their clinical skill development. We argue
      that peer assessment ought to be focused not only on the development of learners'
      clinical skills and knowledge, but also on preparing learners for their
      responsibilities as clinical educators. INNOVATION: Final-year Australian
      osteopathy students in our on-campus university clinic undertook, without
      training, peer assessment and provision of feedback related to clinical
      performance using a discipline-specific adaptation of the mini-CEX. The current
      study suggests that students are able to judge another's consultation skills and
      case management in that they identify what we know are common learning issues for
      students at this level. Peer assessment ought to be focused on preparing learners
      for their responsibilities as clinical educators IMPLICATION: Students may be
      willing to engage in peer assessment if they see the exercise as a way to improve
      patient care and to develop their skills as educators - potentially encouraging
      them to become clinical educators in the future.

PMID- 27878963
TI  - Emergency medicine: An untilled field of public health.

PMID- 27878958
TI  - Inhibition of Orai1-mediated Ca2+ entry enhances chemosensitivity of HepG2
      hepatocarcinoma cells to 5-fluorouracil.
AB  - Increasing evidence supports that activation of store-operated Ca2+ entry (SOCE)
      is implicated in the chemoresistance of cancer cells subjected to chemotherapy.
      However, the molecular mechanisms underlying chemoresistance are not well
      understood. In this study, we aim to investigate whether 5-FU induces
      hepatocarcinoma cell death through regulating Ca2+ -dependent autophagy. [Ca2+ ]i
      was measured using fura2/AM dye. Protein expression was determined by Western
      blotting and immunohistochemistry. We found that 5-fluorouracil (5-FU) induced
      autophagic cell death in HepG2 hepatocarcinoma cells by inhibiting PI3K/AKT/mTOR
      pathway. Orai1 expression was obviously elevated in hepatocarcinoma tissues. 5-FU
      treatment decreased SOCE and Orai1 expressions, but had no effects on Stim1 and
      TRPC1 expressions. Knockdown of Orai1 or pharmacological inhibition of SOCE
      enhanced 5-FU-induced inhibition of PI3K/AKT/mTOR pathway and potentiated 5-FU
      activated autophagic cell death. On the contrary, ectopic overexpression of Orai1
      antagonizes 5-FU-induced autophagy and cell death. Our findings provide
      convincing evidence to show that Orai1 expression is increased in hepatocarcinoma
      tissues. 5-FU can induce autophagic cell death in HepG2 hepatocarcinoma cells
      through inhibition of SOCE via decreasing Orai1 expression. These findings
      suggest that Orai1 expression is a predictor of 5-FU sensitivity for
      hepatocarcinoma treatment and blockade of Orai1-mediated Ca2+ entry may be a
      promising strategy to sensitize hepatocarcinoma cells to 5-FU treatment.

PMID- 27878964
TI  - In this December issue.

PMID- 27878965
TI  - A simplified procedure for antibody engineering by yeast surface display:
      Coupling display levels and target binding by ribosomal skipping.
AB  - Yeast surface display is a valuable, widely used method for protein engineering.
      However, current yeast display applications rely on the staining of epitope tags
      in order to verify full-length presentation of the protein of interest on the
      cell surface. We aimed at developing a modified yeast display approach that
      relies on ribosomal skipping, thereby enabling the translation of two proteins
      from one open reading frame and, in that manner, generating an intracellular
      fluorescence signal. This improved setup is based on a 2A sequence that is
      encoded between the protein to be displayed and a gene for green fluorescent
      protein (GFP). The intracellular GFP fluorescence signal of yeast cells
      correlates with full-length protein presentation and omits the need for the
      immunofluorescence detection of epitope tags. For method validation, shark
      derived IgNAR variable domains (vNAR) were subjected to affinity maturation using
      the 2A-GFP system. Yeast library screening of full-length vNAR variants which
      were detected via GFP expression yielded the same high-affinity binder that had
      previously been isolated by our group using the conventional epitope tag-based
      display format. The presented method obviates the need for additional
      immunofluorescence cell staining, offering an easy and cost-friendly alternative
      to conventional epitope tag detections.

PMID- 27878966
TI  - Risk-adapted stratification for optimally intensive treatment assignment of
      pediatric patients with non-Hodgkin lymphoma is an effective strategy in
      developing countries.
AB  - BACKGROUND: Pediatric patients with non-Hodgkin lymphoma (NHL) in developing
      countries (DCs) present with greater tumor load even at lower stages and with
      comorbidities that impact therapy delivery. This causes toxic mortality with
      "standard" intensive protocols or recurrences with "gentler" treatment.
      OBJECTIVES: We developed and evaluated a risk stratification schema that guides
      intensity of therapy. DESIGN/METHODS: Sixty-nine patients were prospectively
      assigned to five risk groups (A-E; n = 6, 15, 16, 15, and 17) following staging
      and treated with protocols of risk-stratified intensity. Risk stratification
      utilized St. Jude stage, disease bulk, and sites involved. RESULTS: Between 2006
      and 2011, 69 patients with B-cell NHL were enrolled. Among these, 72.5% were boys
      with mean age of 6.9 years (+/-3.33 [SD]; range 2.4-14.2 years). Eighty-seven
      percent had Burkitt lymphoma, 82.6% had advanced stage (25 [36.2%] stage III; 32
      [46.4%] stage IV), and 24.6% were central nervous system positive. Mean lactate
      dehydrogenase increased progressively across the risk strata. Among these, 0/6,
      1/15, 3/16, 2/15, and 7/17 patients relapsed/progressed within each risk stratum.
      Fifteen patients died; three from treatment-related toxicity. At a median follow
      up of 6.2 years, the overall and event-free survival (EFS) for all patients was
      78.1 and 75.4%, respectively; EFS was related to risk assignment. The frequency
      of documented infectious and noninfectious toxicities increased with higher risk
      group assignment causing prolongation of admissions and potential treatment
      delays. CONCLUSIONS: Reduction in treatment intensity for an identified subset of
      patients with NHL is feasible, while high-intensity therapy is required for high
      risk groups. This risk stratification system may be a first step toward improving
      the outcomes in some DCs.

PMID- 27878967
TI  - Synthesis, cytotoxic activity, and 2D- and 3D-QSAR studies of 19-carboxyl
      modified novel isosteviol derivatives as potential anticancer agents.
AB  - Two series of novel acylthiosemicarbazide and oxadiazole fused-isosteviol
      derivatives were synthesized based on the 19-carboxyl modification. The target
      compounds were evaluated for their cytotoxicities against three cancer cell lines
      (HCT-116, HGC-27, and JEKO-1) using an MTT assay. Lead compounds from the
      acylthiosemicarbazides (4) showed IC50 values in the lower micromolar range. For
      example, compounds (4i, 4l, 4m, 4r, and 4s) exhibited significant inhibitory
      activities against the three cell lines with IC50 values of 0.95-3.36 MUm.
      Furthermore, 2D-HQSAR and 3D-topomer CoMFA analyses were established, which could
      be used to develop second generation of isosteviol derivatives as anticancer
      agents.

PMID- 27878969
TI  - Readiness for discharge from subacute mental health units for older people: Using
      available measures to support clinical decision-making.
AB  - Prior to introduction of the Health of the Nation Outcome Scale 65+ (HoNOS65) as
      a mandated measure, the three subacute mental health units for older people in
      the present study routinely used the Care Planning Assessment Tool (CPAT) for
      clinical review and discharge planning. The aims of the present study were to
      compare these two measures of behavioural change during subacute admissions, to
      examine associations with discharge readiness, and to assess their overall
      contributions to discharge planning decisions. This is a prospective, comparative
      measurement study. HoNOS65 (severity) and CPAT (frequency) behavioural subscale
      ratings were collected from admission to discharge for older patients with very
      severe and persistent behavioural and psychological symptoms of dementia.
      Readiness for discharge data (yes/no), collected from multidisciplinary review
      meetings, was used as the outcome in all analyses. In combination, these measures
      achieved only modest positive predictive value (52.8%) but good negative
      predictive value (90.4%). Consequently, patients above the cut-point on both
      measures are reasonably unlikely to be discharge ready. The combined use of a
      standard outcome measure of severity along with a specialized measure of
      frequency is recommended to support and enhance discharge planning decisions in
      this population.

PMID- 27878968
TI  - Proprotein convertase inhibition promotes ciliated cell differentiation - a
      potential mechanism for the inhibition of Notch1 signalling by decanoyl-RVKR
      chloromethylketone.
AB  - Chronic repetitive rounds of injury and repair in the airway lead to airway
      remodelling, including ciliated cell loss and mucous cell hyperplasia. Airway
      remodelling is mediated by many growth and differentiation factors including
      Notch1, which are proteolytically processed by proprotein convertases (PCs). The
      present study evaluated a novel approach for controlling basal cell-type
      determination based on the inhibition of PCs. It was found that decanoyl-RVKR
      chloromethylketone (CMK), a PC inhibitor, promotes ciliated cell differentiation
      and has no effect on the ciliary beat frequency in air-liquid interface (ALI)
      cultures of human nasal epithelial cells (HNECs). Comparative microarray analysis
      revealed that CMK considerably increases ciliogenesis-related gene expression.
      Use of cell-permeable and cell-impermeable PC inhibitors suggests that
      intracellular PCs regulate basal cell-type determination in ALI culture.
      Furthermore, CMK effect on ciliated cell differentiation was reversed by a Notch
      inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester
      (DAPT). CMK inhibited the processing of Notch1, a key regulator of basal cell
      differentiation toward secretory cell lineages in the airway epithelium, and down
      regulated the expression of Notch1 target genes together with furin, a PC.
      Specific lentiviral shRNA-mediated knockdown of furin resulted in reduced Notch1
      processing and increased numbers of ciliated cells in HNECs. Moreover, CMK
      inhibited Notch1 processing and promoted regeneration and ciliogenesis of the
      mouse nasal respiratory epithelium after ZnSO4 injury. These observations suggest
      that PC inhibition promotes airway ciliated cell differentiation, possibly
      through suppression of furin-mediated Notch1 processing. (c) 2016 The Authors
      Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley &
      Sons Ltd.

PMID- 27878970
TI  - Association between the dietary inflammatory index (DII) and telomere length and
      C-reactive protein from the National Health and Nutrition Examination Survey-1999
      2002.
AB  - SCOPE: Leukocyte telomere length (LTL) is an important biomarker of aging. This
      study examined whether inflammatory potential of diet, as measured by the Dietary
      Inflammatory IndexTM (DII) has an impact on telomere shortening in the National
      Health and Nutrition Examination Survey (NHANES). We also carried out validation
      of the DII with C-reactive protein (CRP). METHODS AND RESULTS: Data came from
      NHANES 1999-2002. LTL and CRP were assayed from leukocyte DNA and serum
      specimens, respectively. The DII was calculated from food intakes assessed using
      24-h dietary recalls and expressed per 1000 calories consumed. Associations were
      examined using survey-based multivariable linear regression for log-transformed
      LTL. After multivariable adjustment, higher DII scores (i.e. relatively more pro
      inflammatory) were associated with shorter LTL both when used as continuous (b  =
      -0.003; 95% confidence interval [CI]  =  -0.005, -0.0002) and as quartiles
      (bDIIquartile4vs1   =  -0.013; 95% CI  =  -0.025, -0.001; Ptrend   =  .03). In
      this same sample the DII also was associated with CRP >=3 mg/L (ORDIIcontinuous =
      1.10; 95% CI = 1.06, 1.16). CONCLUSION: In these NHANES data there was an
      association between DII and LTL. This study also provided a successful construct
      validation of the DII using CRP in a nationally representative sample. These
      results are consistent with the hypothesis that diet-associated inflammation
      determines LTL.

PMID- 27878972
TI  - The Interrater Reliability of Nursing Outcome Classification (NOC): "Caregiver
      Performance: Direct Care".
AB  - PURPOSE: The article investigates the interrater reliability of Nursing Outcome
      Classification (NOC) "Caregiver Performance: Direct Care" in Indonesian language.
      METHODS: Two raters assessed 31 caregivers of clients with mental disorders using
      NOC "Caregiver Performance: Direct Care" in January 2016. This NOC was translated
      into Indonesian and each indicator was operated in accordance with caregivers'
      need in taking care of clients. Kappa and percent agreement were used for the
      analysis. FINDINGS: The overall kappa value of NOC "Caregiver Performance: Direct
      Care" was 0.752, while the percent agreement was 80. CONCLUSIONS: The interrater
      reliability of NOC "Caregiver Performance: Direct Care" in Indonesian was at the
      level of substantial reliability. IMPLICATION FOR NURSING PRACTICE: NOC
      "Caregiver Performance: Direct Care" can be used in the clinical setting.

PMID- 27878971
TI  - Pregnane X receptors regulate CYP2C8 and P-glycoprotein to impact on the
      resistance of NSCLC cells to Taxol.
AB  - Cytochrome P450 2C8 (CYP2C8) is one of the enzymes that primarily participate in
      producing metabolisms of medications and P-glycoprotein (P-gp) has been regarded
      as one of the important molecules in chemotherapeutically induced multidrug
      resistance (MDR). In addition, the pregnane X receptor (PXR) is involved in
      regulating both CYP2C8 and P-gp. We aim to research the effect of PXR on Taxol
      resistant non-small-cell lung cancer (NSCLC cells) via regulating CYP2C8 and P
      gp. NSCLC cells were treated with SR12813, LY335979, or PXR siRNA. Cell counting
      kit (CCK-8) assay was used to detect cell vitality. Colony formation assay was
      used to observe cell proliferation. Western blotting, real-time polymerase chain
      reaction (RT-PCR), and immunofluorescence staining were conducted to analyze the
      expressions of PXR, CYP2C8, and P-gp. Taxol and its metabolic products were
      detected by high-performance liquid chromatography (HPLC). The expression of PXR
      in A549 cell line was higher than that in other cell lines. The accumulation of
      PXR was observed in the nucleus after cells were treated with SR12813. Besides,
      SR12813 induced higher expressions of CYP2C8 and P-gp proteins. We also
      discovered that pretreatment with SR12813 reversed the inhibition of cell
      viability and proliferation after the Taxol treatment in comparison to the
      SR12813 untreated group. Furthermore, the hydroxylation products of Taxol
      analyzed by HPLC were increased in comparison to the SR12813 untreated group,
      indicating that high expressions of CYP2C8 and P-gp enhanced the resistance of
      A549 cells to Taxol. For cells treated with PXR siRNA, cell viability, cell
      proliferation, and Taxol metabolites were significantly reduced after the Taxol
      treatment in comparison to the siRNA-negative group. The cell viability, cell
      proliferation, and Taxol metabolites were regulated by the expressions of PXR, P
      gp, and CYP2C8. That is, PXR expression has an important effect on the resistance
      of NSCLC cells to Taxol via upregulating P-gp and CYP2C8.

PMID- 27878973
TI  - Metabolite labelling reveals hierarchies in Clostridium acetobutylicum that
      selectively channel carbons from sugar mixtures towards biofuel precursors.
AB  - Clostridial fermentation of cellulose and hemicellulose relies on the cellular
      physiology controlling the metabolism of the cellulosic hexose sugar (glucose)
      with respect to the hemicellulosic pentose sugars (xylose and arabinose) and the
      hemicellulosic hexose sugars (galactose and mannose). Here, liquid chromatography
      mass spectrometry and stable isotope tracers in Clostridium acetobutylicum were
      applied to investigate the metabolic hierarchy of glucose relative to the
      different hemicellulosic sugars towards two important biofuel precursors, acetyl
      coenzyme A and butyryl-coenzyme A. The findings revealed constitutive metabolic
      hierarchies in C. acetobutylicum that facilitate (i) selective investment of
      hemicellulosic pentoses towards ribonucleotide biosynthesis without substantial
      investment into biofuel production and (ii) selective contribution of
      hemicellulosic hexoses through the glycolytic pathway towards biofuel precursors.
      Long-term isotopic enrichment demonstrated incorporation of both pentose sugars
      into pentose-phosphates and ribonucleotides in the presence of glucose. Kinetic
      labelling data, however, showed that xylose was not routed towards the biofuel
      precursors but there was minor contribution from arabinose. Glucose hierarchy
      over the hemicellulosic hexoses was substrate-dependent. Kinetic labelling of
      hexose-phosphates and triose-phosphates indicated that mannose was assimilated
      but not galactose. Labelling of both biofuel precursors confirmed this metabolic
      preference. These results highlight important metabolic considerations in the
      accounting of clostridial mixed-sugar utilization.

PMID- 27878974
TI  - Evidence for Circulation of Bovine Viral Diarrhoea Virus Type 2c in Ruminants in
      Southern Italy.
AB  - Recently, bovine viral diarrhoea virus type 2c (BVDV-2c) was responsible for a
      severe outbreak in cattle in northern Europe. Here, we present the results of an
      epidemiological survey for pestiviruses in ruminants in southern Italy. Pooled
      serum samples were obtained from 997 bovine, 800 ovine, 431 caprine and eight
      bubaline farms, and pestiviral RNA was detected by molecular methods in 44 farms
      consisting of 16 cattle and one buffalo herds and of 21 sheep and six goat
      flocks. Twenty-nine and 15 farms were infected by BVDV-1 and BVDV-2 strains,
      respectively. BVDV-1 strains were recovered mainly from cattle and were
      heterogeneous, belonging to the subtypes 1b, 1u, 1e, 1g and 1h. In contrast, all
      BVDV-2 viruses but two were detected in sheep or goats and were characterized as
      BVDV-2c by sequence analysis of 5'UTR. These strains displayed high genetic
      identity to BVDV-2c circulating in cattle in northern Europe and were more
      distantly related to a BVDV-2c isolate recovered from a cattle herd in southern
      Italy more than 10 years before. The circulation of a BVDV-2c in small ruminants
      suggests the need for a continuous surveillance for the emergence of pestivirus
      induced clinical signs in southern Italian farms.

PMID- 27878975
TI  - Multiplex RT-PCR and Automated Microarray for Detection of Eight Bovine Viruses.
AB  - Microarrays can be a useful tool for pathogen detection as it allow for
      simultaneous interrogation of the presence of a large number of genetic sequences
      in a sample. However, conventional microarrays require extensive manual handling
      and multiple pieces of equipment for printing probes, hybridization, washing and
      signal detection. In this study, a reverse transcription (RT)-PCR with an
      accompanying novel automated microarray for simultaneous detection of eight
      viruses that affect cattle [vesicular stomatitis virus (VSV), bovine viral
      diarrhoea virus type 1 and type 2, bovine herpesvirus 1, bluetongue virus,
      malignant catarrhal fever virus, rinderpest virus (RPV) and parapox viruses] is
      described. The assay accurately identified a panel of 37 strains of the target
      viruses and identified a mixed infection. No non-specific reactions were observed
      with a panel of 23 non-target viruses associated with livestock. Vesicular
      stomatitis virus was detected as early as 2 days post-inoculation in oral swabs
      from experimentally infected animals. The limit of detection of the microarray
      assay was as low as 1 TCID50 /ml for RPV. The novel microarray platform automates
      the entire post-PCR steps of the assay and integrates electrophoretic-driven
      capture probe printing in a single user-friendly instrument that allows array
      layout and assay configuration to be user-customized on-site.

PMID- 27878976
TI  - Designing research funding schemes to promote global health equity: An
      exploration of current practice in health systems research.
AB  - International research is an essential means of reducing health disparities
      between and within countries and should do so as a matter of global justice.
      Research funders from high-income countries have an obligation of justice to
      support health research in low and middle-income countries (LMICs) that furthers
      such objectives. This paper investigates how their current funding schemes are
      designed to incentivise health systems research in LMICs that promotes health
      equity. Semi-structured in-depth interviews were performed with 16 grants
      officers working for 11 funders and organisations that support health systems
      research: the Alliance for Health Policy and Systems Research, Comic Relief,
      Doris Duke Foundation, European Commission, International Development Research
      Centre, Norwegian Agency for Development Cooperation, Research Council of Norway,
      Rockefeller Foundation, UK Department of International Development, UK Medical
      Research Council, and Wellcome Trust. Thematic analysis of the data demonstrates
      their funding schemes promote health systems research with (up to) five key
      features that advance health equity: being conducted with worst-off populations,
      focusing on research topics that advance equitable health systems, having LMIC
      ownership of the research agenda, strengthening LMIC research capacity, and
      having an impact on health disparities. The different types of incentives that
      encouraged proposed projects to have these features are identified and classified
      by their strength (strong, moderate, weak). It is suggested that research funders
      ought to create and maintain funding schemes with strong incentives for the
      features identified above in order to more effectively help reduce global health
      disparities.

PMID- 27878978
TI  - Elimination of Power Overshoot at Bioanode through Assistance Current in
      Microbial Fuel Cells.
AB  - The power overshoot generated by electron depletion in microbial fuel cells
      (MFCs) was characterized in this study. Various causes of power overshoot,
      identified in previous studies, are discussed in terms of their plausible
      contributions to electron depletion. We found that power overshoot occurred if
      the anodic overpotential generated by electron depletion exceeded the cathodic
      overpotential. The introduction of assistance current from anode connections,
      which ameliorated the electron depletion in the MFCs, immediately eliminated the
      power overshoot. As a result, if the electron production at the anode exceeded
      electron reduction at the cathode, a power overshoot was not generated. The
      results revealed that introducing assistance current supplied from an additional
      anode to the limited anode eliminated power overshoot. The power overshoot is not
      generated by kinetic limitation at the cathode; it is only generated by the
      kinetic limitation at the anode. The mechanism underlying power overshoot should
      be considered in the design of MFCs to improve reliability, particularly in
      scaled-up plant applications. The proposed technique is more practical than
      previously proposed methods.

PMID- 27878977
TI  - Silk fibroin scaffolds with muscle-like elasticity support in vitro
      differentiation of human skeletal muscle cells.
AB  - Human adult skeletal muscle has a limited ability to regenerate after injury and
      therapeutic options for volumetric muscle loss are few. Technologies to enhance
      regeneration of tissues generally rely upon bioscaffolds to mimic aspects of the
      tissue extracellular matrix (ECM). In the present study, silk fibroins from four
      Lepidoptera (silkworm) species engineered into three-dimensional scaffolds were
      examined for their ability to support the differentiation of primary human
      skeletal muscle myoblasts. Human skeletal muscle myoblasts (HSMMs) adhered,
      spread and deposited extensive ECM on all the scaffolds, but immunofluorescence
      and quantitative polymerase chain reaction analysis of gene expression revealed
      that myotube formation occurred differently on the various scaffolds. Bombyx mori
      fibroin scaffolds supported formation of long, well-aligned myotubes, whereas on
      Antheraea mylitta fibroin scaffolds the myotubes were thicker and shorter.
      Myotubes were oriented in two perpendicular layers on Antheraea assamensis
      scaffolds, and scaffolds of Philosamia/Samia ricini (S. ricini) fibroin poorly
      supported myotube formation. These differences were not caused by fibroin
      composition per se, as HSMMs adhered to, proliferated on and formed striated
      myotubes on all four fibroins presented as two-dimensional fibroin films. The
      Young's modulus of A. mylitta and B. mori scaffolds mimicked that of normal
      skeletal muscle, but A. assamensis and S. ricini scaffolds were more flexible.
      The present study demonstrates that although myoblasts deposit matrix onto
      fibroin scaffolds and create a permissive environment for cell proliferation, a
      scaffold elasticity resembling that of normal muscle is required for optimal
      myotube length, alignment, and maturation. (c) 2016 The Authors Journal of Tissue
      Engineering and Regenerative Medicine Published by John Wiley & Sons Ltd.
      StartCopTextStartCopText(c) 2016 The Authors Journal of Tissue Engineering and
      Regenerative Medicine Published by John Wiley & Sons Ltd.

PMID- 27878979
TI  - Prevalence of the Novel Torque Teno Sus Virus Species k2b from Pigs in the United
      States and Lack of Association with Post-Weaning Multisystemic Wasting Syndrome
      or Mulberry Heart Disease.
AB  - The family Anelloviridae includes a number of viruses infecting humans (Torque
      teno viruses, TTV) and other animals including swine (Torque teno sus viruses,
      TTSuV). Two genetically distinct TTSuV species have been identified from swine
      thus far (TTSuV1 and TTSuVk2), although their definitive association with disease
      remains debatable. In 2012, a novel TTSuV species was identified from commercial
      swine serum and classified in the genus Kappatorquevirus as TTSuVk2b. The other
      Kappatorquevirus species, TTSuVk2a, has been associated with post-weaning
      multisystemic wasting syndrome (PMWS) when coinfected with porcine circovirus
      type 2 (PCV2). Therefore, in this study, we initially amplified a portion of
      TTSuVk2b ORF1 and, subsequently, assessed the molecular prevalence of the virus
      in pigs in the United States. A total of 127 serum and 115 tissue samples were
      obtained from pigs with PMWS or mulberry heart disease (MHD) in six states and
      tested by PCR for the presence of TTSuVk2b DNA. Approximately 27.6% of the serum
      and 21.7% of tissue samples tested positive for TTSuVk2b DNA, and the positive
      products were confirmed by sequencing. However, we did not detect a correlation
      between TTSuVk2b infection and PMWS or MHD. The near full-length genomic sequence
      of US TTSuVk2b was determined, and sequence analysis revealed that the US
      TTSuVk2b isolates were 95% identical to the TTSuVk2b isolate from Spain, with
      most of the variations clustering in ORF1. We conclude that the novel TTSuVk2b
      species is present in pigs in the United States and its potential association
      with a disease warrants further investigation.

PMID- 27878980
TI  - Cost-Effectiveness of Mass Dog Vaccination Campaigns against Rabies in Flores
      Island, Indonesia.
AB  - A dynamic deterministic simulation model was developed to determine the cost
      effectiveness of different mass dog vaccination strategies against rabies in a
      dog population representative of a typical village on Flores Island. Cost
      effectiveness was measured as public cost per averted dog-rabies case.
      Simulations started with the introduction of one infectious dog into a
      susceptible dog population of 399 dogs and subsequently ran for a period of 10
      years. The base scenario represented a situation without any control
      intervention. Evaluated vaccination strategies were as follows: annual
      vaccination campaigns with short-acting vaccine (immunity duration of 52 weeks)
      (AV_52), annual campaigns with long-acting vaccine (immunity duration of 156
      weeks) (AV_156), biannual campaigns with short-acting vaccine (BV_52) and once-in
      2-years campaigns with long-acting vaccine (O2V_156). The effectiveness of the
      vaccination strategies was simulated for vaccination coverages of 50% and 70%.
      Cumulative results were reported for the 10-year simulation period. The base
      scenario resulted in three epidemic waves, with a total of 1274 dog-rabies cases.
      The public cost of applying AV_52 at a coverage of 50% was US$5342 for a village.
      This strategy was unfavourable compared to other strategies, as it was costly and
      ineffective in controlling the epidemic. The costs of AV_52 at a coverage of 70%
      and AV_156 at a coverage of 70% were, respectively, US$3646 and US$3716,
      equivalent to US$3.00 and US$3.17 per averted dog-rabies case. Increasing the
      coverage of AV_156 from 50% to 70% reduced the number of cases by 7% and reduced
      the cost by US$1452, resulting in a cost-effectiveness ratio of US$1.81 per
      averted dog-rabies case. This simulation model provides an effective tool to
      explore the public cost-effectiveness of mass dog vaccination strategies in
      Flores Island. Insights obtained from the simulation results are useful for
      animal health authorities to support decision-making in rabies-endemic areas,
      such as Flores Island.

PMID- 27878982
TI  - HLA-DQB1*03:01:34, a novel allele, which has arisen by silent mutation in codon
      87.
AB  - HLA-DQB1*03:01:34 has one nucleotide change from HLA- DQB1*03:01:01 at nucleotide
      357 bp where C>A in exon 2.

PMID- 27878981
TI  - Migration of breast cancer cell lines in response to pulmonary laminin 332.
AB  - Because tumor cell motility is a requirement for metastasis, we hypothesized that
      lung tissue harbors substances that induce tumor cell migration. MCF-7 breast
      carcinoma cells exposed to small airway epithelial cells and conditioned medium
      exhibited dose-dependent tumor cell migration. Among the extracellular matrix
      proteins in the conditioned medium identified by mass spectrometry, laminin 332
      (LM332) had the greatest contribution to the migration of MCF-7 cells.
      Immunoblotting and immunohistochemistry for LM332-specific chains identified
      LM332 in the lung and in pulmonary epithelial cells. Antibodies to either LM332
      or its integrin receptor inhibited MCF-7 motility, and knockdown of LM332 chains
      also reduced its migration-inducing activity. Taken together, these findings
      implicate LM332 as a component of lung tissue that can induce motility in breast
      carcinoma cells that have been transported to lung during metastasis. Earlier
      studies on LM332 in tumor progression have examined LM332 expression in tumor
      cells. This investigation, in comparison, provides evidence that the tumor
      promoting potential of LM332 may originate in the lung microenvironment rather
      than in tumor cells alone. Furthermore, this study provides evidence that the
      motility-inducing properties of the microenvironment can reside in epithelial
      cells. The findings raise the possibility that LM332 plays a role in the
      pulmonary metastases of breast carcinoma and may provide a target for
      antimetastasis therapy.

PMID- 27878985
TI  - HLA-A*30:99 shows a new amino acid position 156 within HLA-A*30 subtypes.
AB  - A novel HLA-A*30:99 allele was characterized in a Spanish individual.

PMID- 27878984
TI  - Sulforaphane-induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC-05.
AB  - BACKGROUND: Xuanwei district in Yunnan Province has the highest incidence of lung
      cancer in China, especially among non-smoking women. Cruciferous vegetables can
      reduce lung cancer risk by prompting a protective mechanism against respiratory
      tract inflammation caused by air pollution, and are rich in sulforaphane, which
      can induce changes in gene expression. We investigated the effect of sulforaphane
      induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL-05) to explore
      the value of sulforaphane in lung cancer prevention and treatment. METHODS: Cell
      growth inhibition was determined by methyl thiazolyl tetrazolium assay; cell
      morphology and apoptosis were observed under transmission electron microscope;
      cell cycle and apoptosis rates were detected using flow cytometry; B-cell
      lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax) messenger RNA expression were
      determined by quantitative PCR; and p53, p73, p53 upregulated modulator of
      apoptosis (PUMA), Bax, Bcl-2, and caspase-9 protein expression were detected by
      Western blotting. RESULTS: Sulforaphane inhibited XWLC-05 cell growth with
      inhibitory concentration (IC)50 of 4.04, 3.38, and 3.02 MUg/mL at 24, 48, and 72
      hours, respectively. Sulforaphane affected the XWLC-05 cell cycle as cells
      accumulated in the G2/M phase. The proportion of apoptotic cells observed was
      27.6%. Compared with the control, the sulforaphane group showed decreased Bcl-2
      and p53 expression, and significantly increased p73, PUMA, Bax, and caspase-9
      protein expression (P < 0.05). CONCLUSION: Sulforaphane induces Xuanwei lung
      adenocarcinoma cell apoptosis. Its possible mechanism may involve the
      upregulation of p73 expression and its effector target genes PUMA and Bax in lung
      cancer cells, downregulation of the anti-apoptotic gene B cl -2, and activation
      of caspase-9. It may also involve downregulation of the mutant p53 protein.

PMID- 27878983
TI  - Enzymatic Specific Production and Chemical Functionalization of Phenylpropanone
      Platform Monomers from Lignin.
AB  - Enzymatic catalysis is an ecofriendly strategy for the production of high-value
      low-molecular-weight aromatic compounds from lignin. Although well-definable
      aromatic monomers have been obtained from synthetic lignin-model dimers,
      enzymatic-selective synthesis of platform monomers from natural lignin has not
      been accomplished. In this study, we successfully achieved highly specific
      synthesis of aromatic monomers with a phenylpropane structure directly from
      natural lignin using a cascade reaction of beta-O-4-cleaving bacterial enzymes in
      one pot. Guaiacylhydroxylpropanone (GHP) and the GHP/syringylhydroxylpropanone
      (SHP) mixture are exclusive monomers from lignin isolated from softwood
      (Cryptomeria japonica) and hardwood (Eucalyptus globulus). The intermediate
      products in the enzymatic reactions show the capacity to accommodate highly
      heterologous substrates at the substrate-binding sites of the enzymes. To
      demonstrate the applicability of GHP as a platform chemical for bio-based
      industries, we chemically generate value-added GHP derivatives for bio-based
      polymers. Together with these chemical conversions for the valorization of lignin
      derived phenylpropanone monomers, the specific and enzymatic production of the
      monomers directly from natural lignin is expected to provide a new stream in
      "white biotechnology" for sustainable biorefineries.

PMID- 27878987
TI  - Identification and characterization of circular RNAs in zebrafish.
AB  - Circular RNA (circRNA), a class of RNAs with circular structure, has received
      little attention until recently, when some new features and functions were
      discovered. In the present study, we sequenced circRNAs in zebrafish (Danio
      rerio) and identified 3868 circRNAs using three algorithms (find_circ, CIRI,
      segemehl). The analysis of microRNA target sites on circRNAs shows that some
      circRNAs may function as miRNA sponges. Furthermore, we identified the existence
      of reverse complementary sequences in the flanking regions of only 25 (2.64%)
      exonic circRNAs, indicating that the mechanism of zebrafish exonic circRNA
      biogenesis might be different from that in mammals. Moreover, 1122 (29%)
      zebrafish circRNA sequences showed homology with human, mouse and coelacanth
      circRNAs.

PMID- 27878986
TI  - Catechol, a major component of smoke, influences primary root growth and root
      hair elongation through reactive oxygen species-mediated redox signaling.
AB  - Nicotiana attenuata germinates from long-lived seedbanks in native soils after
      fires. Although smoke signals have been known to break seed dormancy, whether
      they also affect seedling establishment and root development remains unclear. In
      order to test this, seedlings were treated with smoke solutions. Seedlings
      responded in a dose-dependent manner with significantly increased primary root
      lengths, due mainly to longitudinal cell elongation, increased numbers of lateral
      roots and impaired root hair development. Bioassay-driven fractionations and NMR
      were used to identify catechol as the main active compound for the smoke-induced
      root phenotype. The transcriptome analysis revealed that mainly genes related to
      auxin biosynthesis and redox homeostasis were altered after catechol treatment.
      However, histochemical analyses of reactive oxygen species (ROS) and the
      inability of auxin applications to rescue the phenotype clearly indicated that
      highly localized changes in the root's redox-status, rather than in levels of
      auxin, are the primary effector. Moreover, H2 O2 application rescued the
      phenotype in a dose-dependent manner. Chemical cues in smoke not only initiate
      seed germination, but also influence seedling root growth; understanding how
      these cues work provides new insights into the molecular mechanisms by which
      plants adapt to post-fire environments.

PMID- 27878988
TI  - Identification of a rhodanese-like protein involved in thiouridine biosynthesis
      in Thermus thermophilus tRNA.
AB  - Incorporation of a sulfur atom into 2-thioribothymidine (s2 T or 5-methyl-2
      thiouridine) at position 54 in thermophile tRNA is accomplished by an elaborate
      system composed of many proteins which confers thermostability to the translation
      system. We identified ttuD (tRNA-two-thiouridine D) as a gene for the synthesis
      of s2 T54 in Thermus thermophilus. The rhodanese-like protein TtuD enhances the
      activity of cysteine desulfurases and receives the persulfide generated by
      cysteine desulfurases in vitro. TtuD also enhances the formation of
      thiocarboxylated TtuB, the sulfur donor for the tRNA sulfurtransferase TtuA.
      Since cysteine desulfurases are the first enzymes in the synthesis of s2 T and
      other sulfur-containing compounds, TtuD has a role to direct sulfur flow to s2 T
      synthesis.

PMID- 27878990
TI  - Hemodynamic-guided heart-failure management using a wireless implantable sensor:
      Infrastructure, methods, and results in a community heart failure disease
      management program.
AB  - BACKGROUND: The real-world impact of remote pulmonary artery pressure (PAP)
      monitoring on New York Heart Association (NYHA) class improvement and heart
      failure (HF) hospitalization rate is presented here from a single center.
      HYPOTHESIS: METHODS: Seventy-seven previously hospitalized outpatients with NYHA
      class III HF were offered PAP monitoring via device implantation in a
      multidisciplinary HF-management program. Prospective effectiveness analyses
      compared outcomes in 34 hemodynamically monitored patients to a group of similar
      patients (n = 32) who did not undergo device implantation but received usual
      care. NYHA class and 6-minute walk testing were assessed at baseline and 90 days.
      All hospitalizations were collected after 6 months of the implantation date
      (average follow-up, 15 months) and compared with the number of hospitalizations
      experienced prior to hemodynamic monitoring. RESULTS: Patients in both groups had
      similar distributions of age, sex, and ejection fraction. After 90 days, 61.8% of
      the monitored patients had NYHA class improvement of >=1, compared with 12.5% in
      the controls (P < 0.001). Distance walked in 6 minutes increased by 54.5 meters
      in the monitored group (253.0 +/- 25.6 meters to 307.4 +/- 26.3 meters; P <
      0.005), whereas no change was seen in the usual-care group. After implantation,
      19.4% of the monitored group had >=1 HF hospitalization, compared with 100% who
      had been hospitalized in the year prior to implantation. The monitored group had
      a significantly lower HF hospitalization rate (0.16; 95% confidence interval:
      0.06-0.35 hospitalizations/patient-year) compared with the year prior (1.0
      hospitalizations/patient-year; P < 0.001). CONCLUSIONS: Hemodynamic-guided HF
      management leads to significant improvements in NYHA class and HF hospitalization
      rate in a real-world setting compared with usual care delivered in a
      comprehensive disease-management program.

PMID- 27878989
TI  - Discovery and biological characterization of potent myeloid cell leukemia-1
      inhibitors.
AB  - : Myeloid cell leukemia 1 (Mcl-1) is an antiapoptotic member of the Bcl-2 family
      of proteins that when overexpressed is associated with high tumor grade, poor
      survival, and resistance to chemotherapy. Mcl-1 is amplified in many human
      cancers, and knockdown of Mcl-1 using RNAi can lead to apoptosis. Thus, Mcl-1 is
      a promising cancer target. Here, we describe the discovery of picomolar Mcl-1
      inhibitors that cause caspase activation, mitochondrial depolarization, and
      selective growth inhibition. These compounds represent valuable tools to study
      the role of Mcl-1 in cancer and serve as useful starting points for the discovery
      of clinically useful Mcl-1 inhibitors. PDB ID CODES: Comp. 2: 5IEZ; Comp. 5:
      5IF4.

PMID- 27878991
TI  - Crimp length decreases in lax tendons due to cytoskeletal tension, but is
      restored with tensional homeostasis.
AB  - Collagen crimp morphology is thought to contribute to the material behavior of
      tendons and may reflect the local mechanobiological environment of tendon cells.
      Following loss of collagen tension in tendons, tenocytes initiate a contraction
      response that shortens tendon length which, in turn, may alter crimp patterns. We
      hypothesized that changes in the crimp pattern of tendons are the result of cell
      based contractions which are governed by relative tautness/laxity of the collagen
      matrix. To determine the relationship between crimp pattern and tensional
      homeostasis, rat tail tendon fascicles (RTTfs) were either allowed to freely
      contract or placed in clamps with 10% laxity for 7 days. The freely contracting
      RTTfs showed a significant decrease in percent crimp length on both day 5 (3.66%)
      and day 7 (7.70%). This decrease in crimp length significantly correlated with
      the decrease in freely contracting RTTf length. Clamped RTTfs demonstrated a
      significant decrease in percent crimp length on day 5 (1.7%), but no significant
      difference in percent crimp length on day 7 (0.57%). The results demonstrate that
      the tendon crimp pattern appears to be under cellular control and is a reflection
      of the local mechanobiological environment of the extracellular matrix. The
      ability of tenocytes to actively alter the crimp pattern of collagen fibers also
      suggests that tenocytes can influence the viscoelastic properties of tendon.
      Understanding the interactions between tenocytes and their extracellular matrix
      may lead to further insight into the role tendon cells play in maintaining tendon
      heath and homeostasis. (c) 2016 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 35:573-579, 2017.

PMID- 27878993
TI  - Forward for ICCP2015 issue of Biopolymers Peptide Science.

PMID- 27878992
TI  - FUSCA3 interacting with LEAFY COTYLEDON2 controls lateral root formation through
      regulating YUCCA4 gene expression in Arabidopsis thaliana.
AB  - Lateral root (LR) development is a post-embryonic organogenesis event that gives
      rise to most of the underground parts of higher plants. Auxin promotes LR
      formation, but the molecular mechanisms involved in this process are still not
      well understood. We analyzed LR formation induced by FUSCA3 (FUS3), a B3 domain
      transcription factor, which may function by promoting auxin biosynthesis during
      this process. We identified FUS3-interacting proteins that function in LR
      formation. In addition, we searched for the common targets of both FUS3 and its
      interacting protein. The role of their interactions in regulating auxin
      accumulation and LR initiation was examined. We identified LEAFY COTYLEDON2
      (LEC2) as an interacting factor of FUS3, and demonstrated that these two
      homologous B3 transcription factors interact to bind to the auxin biosynthesis
      gene YUCCA4 (YUC4) and synergistically activate its transcription during LR
      formation. Furthermore, FUS3 expression is activated by LEC2 in LR initiation.
      The observations indicate that the FUS3-LEC2 complex functions as a key regulator
      in auxin-regulated LR formation. The results of this study provide new
      information for understanding the mechanisms of LR regulation.

PMID- 27878995
TI  - Myostatin serum concentrations are correlated with the severity of knee
      osteoarthritis.
AB  - OBJECTIVE: Myostatin, a member of the transforming growth factor-beta family,
      contributes to joint deterioration in mice. Thus, we aimed to assess the
      correlation of myostatin concentrations with the presence and severity of knee
      osteoarthritis (OA). MATERIAL AND METHODS: We determined serum and synovial fluid
      (SF) myostatin concentrations in a population of 184 patients with knee OA and
      109 healthy controls. RESULTS: The knee OA group presented with higher serum
      myostatin concentrations than the controls. Knee OA patients with KL grade 4
      showed higher serum and SF myostatin concentrations compared with those with KL
      grade 2 and 3. Knee OA patients with KL grade 3 had higher serum and SF myostatin
      concentrations compared with those with KL grade 2. Serum and SF myostatin
      concentrations were significantly correlated with KL grading. CONCLUSION: Serum
      and SF myostatin concentrations were correlated with the presence and severity of
      knee OA.

PMID- 27878994
TI  - Direct observation of a deoxyadenosyl radical in an active enzyme environment.
AB  - 5'-deoxyadenosyl radicals have been proposed as the first common intermediate in
      the molecular reaction mechanism of the family of radical S-adenosyl-l-methionine
      (SAM) enzymes. However, this radical species has not yet been directly observed
      in a catalytically active enzyme environment. In a reduced and SAM-containing
      C140A mutant of the spore photoproduct lyase from Geobacillus
      thermodenitrificans, a mutant with altered catalytic activity, we were able to
      identify an organic radical with pronounced hyperfine structure using electron
      paramagnetic resonance spectroscopy. Guided by quantum-chemical computations at
      the density functional theory level of theory, this radical could be tentatively
      assigned to a deoxyadenosyl radical, which provides first experimental evidence
      for this intermediate in the reaction mechanism of radical SAM enzymes.

PMID- 27878996
TI  - On the Practical Interpretability of Cross-Lagged Panel Models: Rethinking a
      Developmental Workhorse.
AB  - Reciprocal feedback processes between experience and development are central to
      contemporary developmental theory. Autoregressive cross-lagged panel (ARCL)
      models represent a common analytic approach intended to test such dynamics. The
      authors demonstrate that-despite the ARCL model's intuitive appeal-it typically
      (a) fails to align with the theoretical processes that it is intended to test and
      (b) yields estimates that are difficult to interpret meaningfully. Specifically,
      using a Monte Carlo simulation and two empirical examples concerning the
      reciprocal relation between spanking and child aggression, it is shown that the
      cross-lagged estimates derived from the ARCL model reflect a weighted-and
      typically uninterpretable-amalgam of between- and within-person associations. The
      authors highlight one readily implemented respecification that better addresses
      these multiple levels of inference.

PMID- 27878998
TI  - The transition from somatic to germline identity shows conserved and specialized
      features during angiosperm evolution.
AB  - How and why specific plant cells adopt germline identity during ovule development
      has proved challenging to address, and the pathways that are active in the ovules
      of basal/early-divergent angiosperms possessing a multilayered nucellus are still
      unclear. Here, we compare megasporogenesis between two early-divergent
      angiosperms (Annona cherimola and Persea americana) and the evolutionarily
      derived Arabidopsis thaliana, studying the three-dimensional spatial position of
      the megaspore mother cell (MMC), the compositional details of the MMC wall and
      the location of PIN1 expression. Specific wall polymers distinguished the central
      position of the MMC and its meiotic products from surrounding tissues in early
      divergent angiosperms, whereas, in A. thaliana, only callose (in mature MMCs) and
      arabinogalactan proteins (AGPs) (in megaspores) distinguished the germline.
      However, PIN1 expression, which regulates polar auxin transport, was observed
      around the MMC in the single-layer nucellus of A. thaliana and in the
      multilayered nucellus of A. cherimola, or close to the MMC in P. americana. The
      data reveal a similar microenvironment in relation to auxin during
      megasporogenesis in all three species. However, the different wall polymers that
      mark MMC fate in early-divergent angiosperms may reflect a specific response to
      mechanical stress during differentiation, or the specific recruitment of polymers
      to sustain MMC growth.

PMID- 27879000
TI  - Impact of prior permanent pacemaker on long-term clinical outcomes of patients
      undergoing percutaneous coronary intervention.
AB  - BACKGROUND: The impact of permanent pacemaker (PPM) on long-term clinical
      outcomes of patients undergoing percutaneous coronary intervention (PCI) has not
      been studied. HYPOTHESIS: PPM may increase heart failure (HF) burden on patients
      undergoing PCI. METHODS: We recruited consecutive patients undergoing PCI and
      carried out a nested case-control study. Patients with confirmed PPM undergoing
      first PCI were identified and matched by age and sex in 1:1 fashion to patients
      without PPM undergoing first PCI. Clinical data were collected and analyzed. The
      primary endpoint outcomes were all-cause mortality and hospitalization for HF.
      RESULTS: The final analysis included 156 patients. The mean follow-up period was
      4.6 +/- 2.9 years. The overall all-cause mortality was 21.15%, without
      significant difference between the 2 groups (21.79% vs 20.51%; P = 0.85).
      However, the rate of HF-related hospitalization was significantly higher in
      patients with PPM than in controls (26.92% vs 10.26%; P = 0.008). After
      adjustment for hypertension, type 2 diabetes mellitus, hyperlipidemia, chronic
      kidney disease, stroke, left ventricular ejection fraction, brain natriuretic
      peptide, and acute coronary syndrome (ACS), PCI patients with PPM were still
      associated with a greater hospitalization rate for HF (odds ratio: 4.31, 95%
      confidence interval: 0.94-19.80, P = 0.061). Further analysis in the ACS subgroup
      showed VVI-mode pacing enhanced the risk for HF-associated hospitalization
      (adjusted odds ratio: 8.27, 95% confidence interval: 1.37-49.75, P = 0.02).
      CONCLUSIONS: PPM has no effect on all-cause mortality in patients undergoing
      first PCI but significantly increases the HF-associated hospitalization rate,
      especially in ACS patients.

PMID- 27878999
TI  - Experimental evaluation of multiscale tendon mechanics.
AB  - Tendon's primary function is a mechanical link between muscle and bone. The
      hierarchical structure of tendon and specific compositional constituents are
      believed to be critical for proper mechanical function. With increased
      appreciation for tendon importance and the development of various technological
      advances, this review paper summarizes recent experimental approaches that have
      been used to study multiscale tendon mechanics, includes an overview of studies
      that have evaluated the role of specific tissue constituents, and also proposes
      challenges/opportunities facing tendon study. Tendon has been demonstrated to
      have specific structural characteristics (e.g., multi-level hierarchy, crimp
      pattern, helix) and complex mechanical properties (e.g., non-linearity,
      anisotropy, viscoelasticity). Physical mechanisms including uncrimping, fiber
      sliding, and collagen reorganization have been shown to govern tendon mechanical
      responses under both static and dynamic loading. Several tendon constituents with
      relatively small quantities have been suggested to play a role in its mechanics,
      although some results are conflicting. Further research should be performed to
      understand the interplay and communication of tendon mechanical properties across
      levels of the hierarchical structure, and further show how each of these
      components contribute to tendon mechanics. The studies summarized and discussed
      in this review have helped elucidate important aspects of multiscale tendon
      mechanics, which is a prerequisite for analyzing stress/strain transfer between
      multiple scales and identifying key principles of mechanotransduction. This
      information could further facilitate interpreting the functional diversity of
      tendons from different species, different locations, and even different
      developmental stages, and then better understand and identify fundamental
      concepts related to tendon degeneration, disease, and healing. (c) 2017
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      35:1353-1365, 2017.

PMID- 27879001
TI  - Osteoarthritis alters the patellar bones subchondral trabecular architecture.
AB  - Following the principles of "morphology reveals biomechanics," the cartilage
      osseous interface and the trabecular network show defined adaptation in response
      to physiological loading. In the case of a compromised relationship, the ability
      to support the load diminishes and the onset of osteoarthritis (OA) may arise. To
      describe and quantify the changes within the subchondral bone plate (SBP) and
      trabecular architecture, 10 human OA patellae were investigated by CT and micro
      CT. The results are presented in comparison to a previously published dataset of
      10 non-OA patellae which were evaluated in the same manner. The analyzed OA
      samples showed no distinctive mineralization pattern in regards to the
      physiological biomechanics, but a highly irregular disseminated distribution. In
      addition, no regularity in bone distribution and architecture across the
      trabecular network was found. We observed a decrease of material as the bone
      volume and trabecular thickness/number were significantly reduced. In comparison
      to non-OA samples, greatest differences for all parameters were found within the
      first mm of trabecular bone. The differences decreased toward the fifth mm in a
      logarithmic manner. The interpretation of the logarithmic relation leads to the
      conclusion that the main impact of OA on bony structures is located beneath the
      SBP and lessens with depth. In addition to the clear difference in material with
      approximately 12% less bone volume in the first mm in OA patellae, the
      architectural arrangement is more rod-like and isotropic, accounting for an
      architectural decrease in stability and support. (c) 2016 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1982-1989, 2017.

PMID- 27878997
TI  - Corneal epithelial cells function as surrogate Schwann cells for their sensory
      nerves.
AB  - The eye is innervated by neurons derived from both the central nervous system and
      peripheral nervous system (PNS). While much is known about retinal neurobiology
      and phototransduction, less attention has been paid to the innervation of the eye
      by the PNS and the roles it plays in maintaining a functioning visual system. The
      ophthalmic branch of the trigeminal ganglion contains somas of neurons that
      innervate the cornea. These nerves provide sensory functions for the cornea and
      are referred to as intraepithelial corneal nerves (ICNs) consisting of subbasal
      nerves and their associated intraepithelial nerve terminals. ICNs project for
      several millimeters within the corneal epithelium without Schwann cell support.
      Here, we present evidence for the hypothesis that corneal epithelial cells
      function as glial cells to support the ICNs. Much of the data supporting this
      hypothesis is derived from studies of corneal development and the reinnervation
      of the ICNs in the rodent and rabbit cornea after superficial wounds. Corneal
      epithelial cells activate in response to injury via mechanisms similar to those
      induced in Schwann cells during Wallerian Degeneration. Corneal epithelial cells
      phagocytize distal axon fragments within hours of ICN crush wounds. During aging,
      the proteins, lipids, and mitochondria within the ICNs become damaged in a
      process exacerbated by UV light. We propose that ICNs shed their aged and damaged
      termini and continuously elongate to maintain their density. Available evidence
      points to new unexpected roles for corneal epithelial cells functioning as
      surrogate Schwann cells for the ICNs during homeostasis and in response to
      injury. GLIA 2017;65:851-863.

PMID- 27879002
TI  - A study of Culicoides in Rondonia, in the Brazilian Amazon: species composition,
      relative abundance and potential vectors.
AB  - There is very little information available about Culicoides species (Diptera:
      Ceratopogonidae) in the western Brazilian Amazon. However, studies of the fauna
      of this region are essential to knowledge of the species and potential vectors
      within it. Thus, the present study aims to evaluate the abundance, richness and
      composition of Culicoides species in rural areas in the state of Rondonia,
      Brazil. Culicoides specimens were collected in forest and pasture environments in
      the municipality of Porto Velho, using light traps. A total of 1708 individuals
      (1136 females and 572 males) belonging to 33 species were collected; 28 of these
      samples represent new records for the state of Rondonia and include the first
      record of Culicoides contubernalis in Brazil. Culicoides insignis was the most
      abundant species (86.1%). Species richness was greater in forest areas (32
      species, 96.96%), whereas pastures presented the greatest number of Culicoides
      captured (n = 1540, 90.1%). This study shows that Culicoides populations differ
      between forest and pasture environments and indicates that the abundance of C.
      insignis is an important factor in epidemiological vigilance studies in the
      region.

PMID- 27879003
TI  - Risk and Protective Processes Predicting Rural African American Young Men's
      Substance Abuse.
AB  - Informed by a life course perspective, this study tested a cascade model linking
      harsh, unresponsive parenting during childhood to young African American men's
      substance abuse via precocious transitions, economic instability, and future
      orientation. The moderating influence of community disadvantage and romantic
      partner support on the hypothesized pathways was also examined. At the baseline,
      the sample included 505 African American men between ages 19 and 22 years from
      high-poverty rural communities. Follow-up data were collected 18 months after
      baseline. Using structural equation modeling, we identified harsh, unresponsive
      parenting influenced precocious transitions in adolescence, which in turn
      increased economic instability during young adulthood. Economic instability was
      associated with a reduction in future orientation, a proximal influence on
      increases in substance abuse. Also, residence in a disadvantaged community
      amplified the influence of precocious transitions on economic instability and the
      influence of economic instability on future orientation. Involvement with
      supportive romantic partnership evinced a protective effect, attenuating the
      influence of precocious transitions on economic instability and the influence of
      economic instability on a future orientation. This study expands understanding of
      young adults' substance abuse by demonstrating the risk and protective processes
      linking substance abuse to developmental factors across childhood, adolescence,
      and young adulthood.

PMID- 27879004
TI  - Plant domestication and the assembly of bacterial and fungal communities
      associated with strains of the common sunflower, Helianthus annuus.
AB  - Root and rhizosphere microbial communities can affect plant health, but it
      remains undetermined how plant domestication may influence these bacterial and
      fungal communities. We grew 33 sunflower (Helianthus annuus) strains (n = 5) that
      varied in their extent of domestication and assessed rhizosphere and root
      endosphere bacterial and fungal communities. We also assessed fungal communities
      in the sunflower seeds to investigate the degree to which root and rhizosphere
      communities were influenced by vertical transmission of the microbiome through
      seeds. Neither root nor rhizosphere bacterial communities were affected by the
      extent of sunflower domestication, but domestication did affect the composition
      of rhizosphere fungal communities. In particular, more modern sunflower strains
      had lower relative abundances of putative fungal pathogens. Seed-associated
      fungal communities strongly differed across strains, but several lines of
      evidence suggest that there is minimal vertical transmission of fungi from seeds
      to the adult plants. Our results indicate that plant-associated fungal
      communities are more strongly influenced by host genetic factors and plant
      breeding than bacterial communities, a finding that could influence strategies
      for optimizing microbial communities to improve crop yields.

PMID- 27879005
TI  - Transient Distention of Right Posterior Located Sigma, a New Sonographic Sign for
      the Prenatal Diagnosis of Anal Atresia.
AB  - We describe a new sonographic sign for the detection of anal atresia in the early
      midtrimester on transvaginal sonography. In six cases of fetal anal atresia, the
      finding of a transient, distended, and right-sided sigmoid colon was observed at
      13-16 weeks' gestation. Three cases have undergone pregnancy termination due to
      multiple anomalies. In the other three, the colonic distension resolved by 19
      weeks' gestation. In two of these, the finding was isolated, and no other
      anomalies were detected. In all six cases, anal atresia or cloaca was confirmed
      on postabortal autopsy or after delivery. (c) 2016 Wiley Periodicals, Inc. J Clin
      Ultrasound 45:160-162, 2017.

PMID- 27879008
TI  - Quality of life measurement in atopic dermatitis. Position paper of the European
      Academy of Dermatology and Venereology (EADV) Task Force on quality of life.
AB  - There is a need for researchers to have easy reference to the wide spectrum of
      different types of quality of life (QoL) instruments that can be used in atopic
      dermatitis (AD). Previous reviews on QoL in AD do not cover the full spectrum of
      QoL measures used in studies on AD. This study, on behalf of the European Academy
      of Dermatology and Venereology (EADV) Task Force on QoL, contains information on
      instruments available for health-related QoL and family QoL assessment in AD
      including information on validation, experience of QoL assessment in AD for
      different purposes, peculiarities of QoL assessment in different age groups,
      expert analysis of available instruments including data on limitations of their
      use and recommendations of the Task Force.

PMID- 27879009
TI  - Epidemiological, dermoscopical and pathological evaluation of melanocytic lesions
      of the buttock in a 5-year period: a female prevalence.

PMID- 27879007
TI  - Drotaverine - a Concealed Cytostatic!
AB  - Drotaverine (also known as dihydroperparine or No-Spa(r) ) is an antispasmodic
      drug closely related to papaverin. Drotaverin also acts as a cytostatic compound
      for several human tumor cell lines and nonmalignant mouse fibroblasts, and EC50
      values as low as 3.0 MUM were observed in SRB assays for HT-29 human colorectal
      carcinoma cells. Small structural changes (e.g., aromatization, benzylic
      oxidation) led to a reduced activity or a complete loss of cytotoxicity. Staining
      of the cells with acridine orange showed the cell membrane of the dead cells to
      be still intact, and a slight G1/G0 arrest in the treated cells was observed
      after 24 h. Extra annexin V-FITC/PI assays and flow cytometry revealed
      drotaverine mainly to act as a cytostatic and only to a minor extent as cytotoxic
      agent.

PMID- 27879010
TI  - Photochemical Reduction of CO2 with Visible Light Using a Polyoxometalate as
      Photoreductant.
AB  - The photochemical reduction of CO2 to CO requires two electrons and two protons
      that, in the past, have been derived from sacrificial amine donors that are also
      non-innocent in the catalytic cycle. Towards the realization of a water-splitting
      reaction as the source of electrons and protons for CO2 reduction, we have found
      that a reduced acidic polyoxometalate, H5 PWV2 W10 O40 , is a photoactive
      electron and proton donor with visible light through excitation of the
      intervalence charge-transfer band. Upon linking the polyoxometalate to a
      dirhenium molecular catalyst, a cascade of transformations occurs where the
      polyoxometalate is electrochemically reduced at a relatively low negative
      potential of 1.3 V versus Ag/AgNO3 and visible light, a 60 W tungsten lamp, or a
      red LED is used to transfer electrons from the polyoxometalate to the dirhenium
      catalyst active for the selective reduction of CO2 to CO.

PMID- 27879011
TI  - One-Pot Procedure for the Synthesis of 1,5-Benzodiazepines from N-Allyl-2
      bromoanilines.
AB  - A new one-pot procedure that includes an initial titanium-catalyzed
      intermolecular hydroaminoalkylation of N-allyl-2-bromoanilines with N
      methylanilines and a subsequent intramolecular Buchwald-Hartwig amination
      directly gives access to pharmacologically relevant 1,5-benzodiazepines. The
      process takes advantage of the excellent regioselectivity of the initial
      hydroaminoalkylation performed in the presence of a titanium mono(formamidinate)
      catalyst and the fact that the exclusively formed branched hydroaminoalkylation
      products can only undergo palladium-catalyzed cyclization to 1,5-benzodiazepines.

PMID- 27879006
TI  - Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1
      Receptor.
AB  - The cannabinoid CB1 receptor is a G protein coupled receptor and plays an
      important role in many biological processes and physiological functions. A
      variety of CB1 receptor agonists and antagonists, including endocannabinoids,
      phytocannabinoids, and synthetic cannabinoids, have been discovered or developed
      over the past 20 years. In 2005, it was discovered that the CB1 receptor contains
      allosteric site(s) that can be recognized by small molecules or allosteric
      modulators. A number of CB1 receptor allosteric modulators, both positive and
      negative, have since been reported and importantly, they display pharmacological
      characteristics that are distinct from those of orthosteric agonists and
      antagonists. Given the psychoactive effects commonly associated with CB1 receptor
      agonists and antagonists/inverse agonists, allosteric modulation may offer an
      alternate approach to attain potential therapeutic benefits while avoiding
      inherent side effects of orthosteric ligands. This review details the complex
      pharmacological profiles of these allosteric modulators, their structure-activity
      relationships, and efforts in elucidating binding modes and mechanisms of actions
      of reported CB1 allosteric modulators. The ultimate development of CB1 receptor
      allosteric ligands could potentially lead to improved therapies for CB1-mediated
      neurological disorders.

PMID- 27879012
TI  - Crusted impetigo-like lesion on the face: a case of IgG/IgA pemphigus.

PMID- 27879014
TI  - Highly Efficient Reusable Sponge-Type Catalyst Carriers Based on Short
      Electrospun Fibers.
AB  - This study reports on gold nanoparticles (AuNPs) immobilized in a sponge made of
      short electrospun fibers (Au-sponge), which show surprisingly high reaction rates
      at extremely low gold amount. Au-sponges are made by freeze-drying of dispersions
      of short electrospun fibers with preimmobilization of AuNPs. The resulting Au
      sponges show very low densities around 7 mg cm-3 corresponding to a pore volume
      of about 150 mL g-1 , but low surface area and very low amount of AuNPs in the
      range of 0.29-3.56 wt%. In general, catalysts with immobilized AuNPs show much
      low reaction rates compared to systems with dispersed AuNPs. By contrast, the Au
      sponge catalyst with immobilized AuNPs is discerned here as an extremely
      efficient catalyst even superior to other systems with dispersed AuNPs. The
      fidelity of the Au-sponges after reactions is good enough for manifold use and
      thereby provides a sustainable catalyst design as well.

PMID- 27879013
TI  - Bright Multicolor Bandgap Fluorescent Carbon Quantum Dots for Electroluminescent
      Light-Emitting Diodes.
AB  - Multicolor bandgap fluorescent carbon quantum dots (MCBF-CQDs) from blue to red
      with quantum yield up to 75% are synthesized using a solvothermal method. For the
      first time, monochrome electroluminescent light-emitting diodes (LEDs) with MCBF
      CQDs directly as an active emission layer are fabricated. The maximum luminance
      of blue LEDs reaches 136 cd m-2 , which is the best performance for CQD-based
      monochrome electroluminescent LEDs.

PMID- 27879015
TI  - A Quantitative Study of the Effects of Guest Flexibility on Binding Inside a
      Coordination Cage Host.
AB  - We have performed a systematic investigation of the effects of guest flexibility
      on their ability to bind in the cavity of a coordination cage host in water,
      using two sets of isomeric aliphatic ketones that differ only in the branching
      patterns of their alkyl chains. Apart from the expected increase in binding
      strength for C9 over C7 ketones associated with their greater hydrophobic surface
      area, within each isomeric set there is a clear inverse correlation between
      binding free energy and guest flexibility, associated with loss of conformational
      entropy. This can be parameterized by the number of rotatable C-C bonds in the
      guest, with each additional rotatable bond resulting in a penalty of around 2 kJ
      mol-1 in the binding free energy, in good agreement with values obtained from
      protein/ligand binding studies. We used the binding data for the new flexible
      guests to improve the scoring function that we had previously developed that
      allowed us to predict binding constants of relatively rigid guests in the cage
      cavity using the molecular docking programme GOLD (Genetic Optimisation of Ligand
      Docking). This improved scoring function resulted in a significant improvement in
      the ability of GOLD to predict binding constants for flexible guests, without any
      detriment to its ability to predict binding for more rigid guests.

PMID- 27879016
TI  - Pure Formamidinium-Based Perovskite Light-Emitting Diodes with High Efficiency
      and Low Driving Voltage.
AB  - A formamidinium(FA)-based perovskite showns superior optoelectronic properties
      including better stability than methylammonium-based counterparts. Pure FA
      perovskite-based light-emitting diodes (LEDs) with high efficiency are reported.
      Interestingly, the LED clearly shows a sub-bandgap emission at 1.7 V (bandgap 2.3
      eV). This important discovery provides further insights of the charge transport
      mechanism in perovskite-based optoelectronic devices.

PMID- 27879018
TI  - Structural Tuning of Anion-Templated Motifs with External Stimuli through Crystal
      to-Crystal Transformation.
AB  - Protonation of trans-1,2-bis(4-pyridyl)ethylene (4,4'-bpe) with dilute sulfuric
      acid (33 %) afforded a protonated adduct [{4,4'-bpe?2 H+ }2 {HSO4 }-2 {SO4 }-2
      {H2 O}2 ] (1). The neighboring olefinic bond in 1 is in a suitable range (3.931
      4.064 A) to undergo a photochemical [2+2] cycloaddition reaction. Upon
      irradiation with UV light (365 nm), 1 undergoes a molecular sliding involving the
      4,4'-bpe?2 H+ units, affording 2, stabilized through OSO4 ???pi interactions.
      Heating 1 to 50 degrees  C leads to a 3D hydrogen-bonded organic framework (HOF)
      (3). This process occurs through thermal dissociation of the bisulfate anion.
      Diffusion of iodine through the crystal lattice of 1 and 3 enables the reduction
      of sulfate to bisulfate, affording a 1D hydrogen-bonded chain (4). Solid-state 13
      C CPMAS NMR, IR, DSC, and powder XRD studies further support stimuli-responsive
      structural tuning through crystal-to-crystal transformation. All these
      conversions occur with significant translational and rotational movements along
      with a series of bond-breaking and bond-forming processes.

PMID- 27879017
TI  - Domain architecture of vasohibins required for their chaperone-dependent
      unconventional extracellular release.
AB  - Vasohibins (VASH1 and VASH2) are recently identified regulators of angiogenesis
      and cancer cell functions. They are secreted proteins without any classical
      secretion signal sequences, and are thought to be secreted instead via an
      unconventional protein secretion (UPS) pathway in a small vasohibin-binding
      protein (SVBP)-dependent manner. However, the precise mechanism of SVBP-dependent
      UPS is poorly understood. In this study, we identified a novel UPS regulatory
      system in which essential domain architecture (VASH-PS) of VASHs, comprising
      regions VASH191-180 and VASH280-169 , regulate the cytosolic punctate structure
      formation in the absence of SVBP. We also demonstrate that SVBP form a complex
      with VASH1 through the VASH1274-282 (SIa), VASH1139-144 (SIb), and VASH1133-137
      (SIc), leading to the dispersion in the cytosol and extracellular release of
      VASH1. The amino acid sequences of VASH-SIa and VASH-PS, containing SIb and SIc,
      are highly conserved among VASH family members in vertebrates, suggesting that
      SVBP-dependent UPS may be common within the VASH family. This novel UPS
      regulatory system may open up new avenues for understanding fundamental protein
      secretion in vertebrates.

PMID- 27879020
TI  - Membrane protein insertase YidC in bacteria and archaea.
AB  - The insertion of proteins into the prokaryotic plasma membrane is catalyzed by
      translocases and insertases. On one hand, the Sec translocase operates as a
      transmembrane channel that can open laterally to first bind and then release the
      hydrophobic segments of a substrate protein into the lipid bilayer. On the other
      hand, YidC insertases interact with their substrates in a groove-like structure
      at an amphiphilic protein-lipid interface thus allowing the transmembrane
      segments of the substrate to slide into the lipid bilayer. The recently published
      high-resolution structures of YidC provide new mechanistic insights of how
      transmembrane proteins achieve the transition from an aqueous environment in the
      cytoplasm to the hydrophobic lipid bilayer environment of the membrane.

PMID- 27879019
TI  - Screening for ALK abnormalities in central nervous system metastases of non-small
      cell lung cancer.
AB  - Anaplastic lymphoma kinase (ALK) gene rearrangement was reported in 3%-7% of
      primary non-small-cell lung cancer (NSCLC) and its presence is commonly
      associated with adenocarcinoma (AD) type and non-smoking history. ALK tyrosine
      kinase inhibitors (TKIs) such as crizotinib, alectinib and ceritinib showed
      efficiency in patients with primary NSCLC harboring ALK gene rearrangement.
      Moreover, response to ALK TKIs was observed in central nervous system (CNS)
      metastatic lesions of NSCLC. However, there are no reports concerning the
      frequency of ALK rearrangement in CNS metastases. We assessed the frequency of
      ALK abnormalities in 145 formalin fixed paraffin embedded (FFPE) tissue samples
      from CNS metastases of NSCLC using immunohistochemical (IHC) automated staining
      (BenchMark GX, Ventana, USA) and fluorescence in situ hybridization (FISH)
      technique (Abbot Molecular, USA). The studied group was heterogeneous in terms of
      histopathology and smoking status. ALK abnormalities were detected in 4.8%
      (7/145) of CNS metastases. ALK abnormalities were observed in six AD (7.5%; 6/80)
      and in single patients with adenosuqamous lung carcinoma. Analysis of clinical
      and demographic factors indicated that expression of abnormal ALK was
      significantly more frequently observed (P = 0.0002; chi2  = 16.783) in former
      smokers. Comparison of IHC and FISH results showed some discrepancies, which were
      caused by unspecific staining of macrophages and glial/nerve cells, which
      constitute the background of CNS tissues. Their results indicate high frequency
      of ALK gene rearrangement in CNS metastatic sites of NSCLC that are in line with
      prior studies concerning evaluation of the presence of ALK abnormalities in such
      patients. However, they showed that assessment of ALK by IHC and FISH methods in
      CNS tissues require additional standardizations.

PMID- 27879021
TI  - Click and Release: A Chemical Strategy toward Developing Gasotransmitter Prodrugs
      by Using an Intramolecular Diels-Alder Reaction.
AB  - Prodrug strategies have been proven to be a very effective way of addressing
      delivery problems. Much of the chemistry in prodrug development relies on the
      ability to mask an appropriate functional group, which can be removed under
      appropriate conditions. However, developing organic prodrugs of gasotransmitters
      represent unique challenges. This is especially true with carbon monoxide, which
      does not have an easy "handle" for bioreversible derivatization. By taking
      advantage of an intramolecular Diels-Alder reaction, we have developed a prodrug
      strategy for preparations of organic CO prodrugs that are stable during synthesis
      and storage, and yet readily release CO with tunable release rates under near
      physiological conditions. The effectiveness of the CO prodrug system in
      delivering a sufficient quantity of CO for possible therapeutic applications has
      been studied using a cell culture anti-inflammatory assay and a colitis animal
      model. These studies fully demonstrate the proof of concept, and lay a strong
      foundation for further medicinal chemistry work in developing organic CO
      prodrugs.

PMID- 27879022
TI  - Catalytic Emulsion Based on Janus Nanosheets for Ultra-Deep Desulfurization.
AB  - Catalytic Janus nanosheets were synthesized by using an anion-exchange reaction
      between heteropolyacids (HPAs) and the modified ionic-liquid (IL) moieties of
      Janus nanosheets. Their morphology and surface properties were characterized by
      using SEM, energy-dispersive spectroscopy (EDS), FTIR spectroscopy, and X-ray
      photoelectron spectroscopy (XPS) studies. Because of their inherent Janus
      structure, the nanosheets exhibited good amphipathic character with ILs and oil
      to form a stable ILs-in-oil emulsion. Therefore, these Janus nanosheets can be
      used as both emulsifiers and catalysts to perform emulsive desulfurization.
      During this process, sulfur-containing compounds at the interface could be easily
      oxidized and efficiently removed from a model oil. Application of this Janus
      emulsion brings an efficient, useful, and green procedure to the desulfurization
      process. Compared with the desulfurization catalyzed by using HPAs in a
      conventional two-phase system, the sulfur removal of dibenzothiophene (DBT)
      achieved in a Janus emulsion system was improved from 68 to 97 % within 1.5 h.
      Moreover, this emulsion system could be demulsified easily by simple
      centrifugation to recover both the nanosheets and the ILs. Owing to the good
      structural stability of the Janus nanosheets, the sulfur removal efficiency of
      DBT could still reach 99.9 % after the catalytic nanosheets had been recycled at
      least six times.

PMID- 27879023
TI  - Potential effect of ezetimibe against Mycobacterium tuberculosis infection in
      type II diabetes.
AB  - BACKGROUND AND OBJECTIVE: Tuberculosis (TB) risk might be increased in patients
      with diabetes by factors other than hyperglycaemia, such as dyslipidaemia. Host
      lipids are essential energy sources used by mycobacteria to persist in a latent
      TB state. A potential therapy targeting cholesterol catabolism of mycobacteria
      has been proposed, but the potential of cholesterol-lowering drugs as anti-TB
      therapy is unclear. The purpose of this study was to determine the effects of
      ezetimibe, a 2-azetidinone cholesterol absorption inhibitor, on intracellular
      mycobacteria survival and dormancy. METHODS: Intracellular mycobacteria survival
      was determined by measurements of ATP activity and colony-formation units (CFUs).
      Gene expression profiles of hypoxia-induced dormant Mycobacterium tuberculosis
      (Mtb) were analysed by real-time PCR. Flow cytometry and microscopy analysis were
      used to measure the lipid loads of human macrophages with or without ezetimibe
      treatment. QuantiFERON-TB Gold In-Tube (QFT-G-IT) assays were performed to
      diagnose latent TB infection. The levels of intracellular cholesterol/
      triglyceride were measured by an enzymatic fluorometric method. RESULTS:
      Ezetimibe was capable of effectively lowering intracellular growth of Mtb and
      hypoxia-induced dormant Mtb. There was a significant decrease in Mtb growth in
      leucocytes from ezetimibe-treated patients with diabetes in terms of ATP levels
      of intracellular mycobacteria and CFU formation. Also, patients receiving
      ezetimibe therapy had a lower prevalence of latent TB and had lower intracellular
      lipid contents. CONCLUSION: Ezetimibe, which is a currently marketed drug, could
      hold promise as an adjunctive, host-directed therapy for TB.

PMID- 27879025
TI  - Trajectory of Approach of a Zinc-Hydrogen Bond to Transition Metals.
AB  - Through a dramatic advance in the coordination chemistry of the zinc-hydride
      bond, we describe the trajectory for the approach of this bond to transition
      metals. The dynamic reaction coordinate was interrogated through analysis of a
      series of solid state structures and is one in which the TM-H-Zn angle becomes
      increasingly acute as the TM-Zn distance decreases. Parallels may be drawn with
      the oxidative addition of boron-hydrogen and silicon-hydrogen bonds to transition
      metal centers.

PMID- 27879024
TI  - A newly emerged osteosarcomatous dedifferentiation of liposarcoma in lung
      metastasis - a potential diagnostic pitfall.

PMID- 27879026
TI  - Ionizing radiation promotes CCL27 secretion from keratinocytes through the cross
      talk between TNF-alpha and ROS.
AB  - The skin-associated chemokine CCL27 and its receptor CCR10 mediate the immune
      response of skin-homing T cells. The CCL27 secreted from keratinocytes was
      reportedly involved in inflammatory skin diseases such as atopic dermatitis,
      contact dermatitis, and psoriasis. However, whether ionizing radiation increases
      the levels of CCL27 secretion still remains unclear. In HaCaT cells, a human
      keratinocyte cell line, CCL27 secretion was markedly increased after X-ray
      irradiation. We further found that irradiation boosted the generation of reactive
      oxygen species (ROS), which was concomitant with the release of tumor necrosis
      factor-alpha (TNF-alpha). Moreover, alteration of ROS in irradiated HaCaT cells
      correlated with TNF-alpha secretion, indicating a positive loop of TNF-alpha
      secretion and ROS generation. This positive loop regulated the secretion of CCL27
      from irradiated cells. We therefore concluded that the cross talk between TNF
      alpha and ROS after keratinocytes was exposed to radiation, triggered CCL27
      secretion for subsequent inflammation response.

PMID- 27879027
TI  - Arenophile-Mediated Dearomative Reduction.
AB  - A dearomative reduction of simple arenes has been developed which employs a
      visible-light-mediated cycloaddition of arenes with an N-N-arenophile and in situ
      diimide reduction. Subsequent cycloreversion or fragmentation of the arenophile
      moiety affords 1,3-cyclohexadienes or 1,4-diaminocyclohex-2-enes, compounds that
      are not synthetically accessible using existing dearomatization reactions.
      Importantly, this strategy also provides numerous opportunities for further
      derivatization as well as site-selective functionalization of polynuclear arenes.

PMID- 27879028
TI  - The Orange Side of Disperse Red 1: Humidity-Driven Color Switching in
      Supramolecular Azo-Polymer Materials Based on Reversible Dye Aggregation.
AB  - Humidity detection, and the quest for low-cost facile humidity-sensitive
      indicator materials is of great interest for many fields, including semi
      conductor processing, food transport and storage, and pharmaceuticals. Ideal
      humidity-detection materials for a these applications might be based on simple
      clear optical readout with no power supply, i.e.: a clear color change observed
      by the naked eye of any untrained observer, since it doesn't require any extra
      instrumentation or interpretation. Here, the introduction of a synthesis-free one
      step procedure, based on physical mixing of easily available commercial
      materials, for producing a humidity memory material which can be easily painted
      onto a wide variety of surfaces and undergoes a remarkable color change
      (approximately 100 nm blue-shift of lambdaMAX ) upon exposure to various
      thresholds of levels of ambient humidity is reported. This strong color change,
      easily visible to as a red-to-orange color switch, is locked in until inspection,
      but can then be restored reversibly if desired, after moderate heating. By taking
      advantage of spontaneously-forming reversible 'soft' supramolecular bonds between
      a red-colored azo dye and a host polymer matrix, a reversible dye 'migration'
      aggregation appearing orange, and dis-aggregation back to red can be achieved, to
      function as the sensor.

PMID- 27879029
TI  - Progesterone receptor and prostaglandins mediate luteinizing hormone-induced
      changes in messenger RNAs for ADAMTS proteases in theca cells of bovine
      periovulatory follicles.
AB  - Little is known about the ADAMTS (a disintegrin and metalloproteinase with
      thrombospondin motifs) family of extracellular proteases in ovarian follicles of
      non-rodent species, particularly in theca cells. In the present study, temporal
      changes in the abundance of mRNA encoding four ADAMTS subtypes and hormonal
      regulation of mRNA encoding two subtypes were investigated in theca interna cells
      during the periovulatory period in cattle. Gonadotropin-releasing hormone (GnRH)
      was injected into animals to induce a luteinizing hormone (LH)/follicle
      stimulating hormone (FSH) surge, and follicles were obtained at 0 hr post-GnRH
      (preovulatory) or at 6, 12, 18, or 24 hr (periovulatory). ADAMTS1, -2, -7, and -9
      transcript abundance was then determined in the isolated theca interna. ADAMTS1
      and -9 mRNA levels were up-regulated at 24 hr post-GnRH, whereas ADAMTS2 mRNA was
      higher at 12-24 hr post-GnRH and ADAMTS7 mRNA increased transiently at 12 hr post
      GnRH compared to other time points. Subsequent in vitro experiments using
      preovulatory theca interna (0 hr post-GnRH) showed that application of LH in
      vitro can mimic the effects of the gonadotropin surge on mRNAs encoding ADAMTS1
      and -9 and that progesterone/progesterone receptor and/or prostaglandins may
      regulate the levels of mRNA encoding ADAMTS1 and -9 in theca interna, downstream
      of the LH surge. Time- and subtype-specific changes in ADAMTS mRNA abundance in
      vivo, and their regulation in vitro by hormones, indicate that ADAMTS family
      members produced by theca cells may play important roles in follicle rupture and
      the accompanying tissue remodeling in cattle. Mol. Reprod. Dev. 84: 55-66, 2017.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27879031
TI  - Combining Organocatalysis and Lanthanide Catalysis: A Sequential One-Pot
      Quadruple Reaction Sequence/Hetero-Diels-Alder Asymmetric Synthesis of
      Functionalized Tricycles.
AB  - A stereoselective one-pot synthesis of functionalized complex tricyclic
      polyethers has been achieved using the combination of secondary amine and
      lanthanide catalysis. This one-pot quadruple reaction/Hetero-Diels-Alder sequence
      gave good yields (per step) as well as excellent diastereo- and
      enantioselectivities. Furthermore, the particular combination of lanthanide
      complexes with organocatalysis is one of the first examples described for
      sequential catalysis.

PMID- 27879030
TI  - Age-related decline in task switching is linked to both global and tract-specific
      changes in white matter microstructure.
AB  - Task-switching performance relies on a broadly distributed frontoparietal network
      and declines in older adults. In this study, they investigated whether this age
      related decline in task switching performance was mediated by variability in
      global or regional white matter microstructural health. Seventy cognitively
      intact adults (43-87 years) completed a cued-trials task switching paradigm.
      Microstructural white matter measures were derived using diffusion tensor imaging
      (DTI) analyses on the diffusion-weighted imaging (DWI) sequence. Task switching
      performance decreased with increasing age and radial diffusivity (RaD), a measure
      of white matter microstructure that is sensitive to myelin structure. RaD
      mediated the relationship between age and task switching performance. However,
      the relationship between RaD and task switching performance remained significant
      when controlling for age and was stronger in the presence of cardiovascular risk
      factors. Variability in error and RT mixing cost were associated with RaD in
      global white matter and in frontoparietal white matter tracts, respectively.
      These findings suggest that age-related increase in mixing cost may result from
      both global and tract-specific disruption of cerebral white matter linked to the
      increased incidence of cardiovascular risks in older adults. Hum Brain Mapp
      38:1588-1603, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27879032
TI  - Altered expression of BRG1 and histone demethylases, and aberrant H3K4
      methylation in less developmentally competent embryos at the time of embryonic
      genome activation.
AB  - Epigenetics is a fundamental regulator underlying many biological functions, such
      as development and cell differentiation. Epigenetic modifications affect key
      chromatin regulation, including transcription and DNA repair, which are critical
      for normal embryo development. In this study, we profiled the expression of
      epigenetic modifiers and patterns of epigenetic changes in porcine embryos around
      the period of embryonic genome activation (EGA). We observed that Brahma-related
      gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation
      status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of
      development. We then compared the abundance of epigenetic modifiers between early
      and late-cleaving embryos, which were classified based on the time to the first
      cell cleavage, to investigate if their nuclear localization contributes to
      developmental competence. The mRNA abundance of BRG1, KDM1A, as well as other
      lysine demethylases (KDM1B, KDM5A, KDM5B, and KDM5C), were significantly higher
      in late- compared to early-cleaving embryos near the EGA period, although these
      difference disappeared at the blastocyst stage. The abundance of H3K4 mono-
      (H3K4me) and di-methylation (H3K4me2) during the EGA period was reduced in late
      cleaving and less developmentally competent embryos. By contrast, BRG1, KDM1A,
      and H3K4me2 abundance was greater in embryos with more than eight cells at Day 3
      4 of development compared to those with fewer than four cells. These findings
      suggest that altered epigenetic modifications of H3K4 around the EGA period may
      affect the developmental capacity of porcine embryos to reach the blastocyst
      stage. Mol. Reprod. Dev. 84: 19-29, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27879034
TI  - Template-Free Supracolloidal Self-Assembly of Atomically Precise Gold
      Nanoclusters: From 2D Colloidal Crystals to Spherical Capsids.
AB  - We report supracolloidal self-assembly of atomically precise and strictly
      monodisperse gold nanoclusters involving p-mercaptobenzoic acid ligands (Au102 
      pMBA44 ) under aqueous conditions into hexagonally packed monolayer-thick two
      dimensional facetted colloidal crystals (thickness 2.7 nm) and their bending to
      closed shells leading to spherical capsids (d ca. 200 nm), as controlled by
      solvent conditions. The 2D colloidal assembly is driven in template-free manner
      by the spontaneous patchiness of the pMBA ligands around the Au102 -pMBA44
      nanoclusters preferably towards equatorial plane, thus promoting inter
      nanocluster hydrogen bonds and high packing to planar sheets. More generally, the
      findings encourage to explore atomically precise nanoclusters towards highly
      controlled colloidal self-assemblies.

PMID- 27879033
TI  - Regulation of the placental BCRP transporter by PPAR gamma.
AB  - Identifying regulators of placental breast cancer resistance protein (BCRP)
      expression is critical as downregulation of this transporter may increase
      exposure of the fetus to xenobiotics. Here, we sought to test whether the nuclear
      receptor peroxisome proliferator-activated receptor gamma (PPARgamma) regulates
      BCRP expression in the placenta. To test this, human BeWo placental
      choriocarcinoma cells were cultured with the PPARgamma agonist rosiglitazone or
      the PPARgamma antagonist T0070907 for 24 h. Messenger RNA (mRNA) expression of
      syncytialization markers, GCM1 and hCGbeta, as well as BCRP increased with
      PPARgamma agonist treatment. Conversely, BCRP mRNA and protein expression
      decreased 30%-50% with PPARgamma antagonist treatment. Rosiglitazone enhanced
      BCRP protein expression and transport activity, resulting in a 20% greater efflux
      of the substrate Hoechst 33342 compared with control cells. These results suggest
      that PPARgamma can upregulate BCRP expression in the placenta, which may be
      important in understanding mechanisms that protect the fetus from xenobiotic
      exposure during development.

PMID- 27879035
TI  - Dynamic Nuclear Polarization Provides New Insights into Chromophore Structure in
      Phytochrome Photoreceptors.
AB  - Phytochromes are red/far-red photochromic photoreceptors acting as master
      regulators of development in higher plants, thereby controlling transcription of
      about 20 % of their genes. Light-induced isomerization of the bilin chromophore
      leads to large rearrangements in protein structure, whereby the role of
      protonation dynamics and charge distribution is of particular interest. To help
      unravel the inherent mechanisms, we present two-dimensional dynamic nuclear
      polarization (DNP) enhanced solid-state magic-angle spinning (MAS) NMR spectra of
      the functional sensory module of the cyanobacterial phytochrome Cph1. To this
      end, the pyrrole ring nitrogen signals were assigned unequivocally, enabling us
      to locate the positive charge of the phycocyanobilin (PCB) chromophore. To help
      analyze proton exchange pathways, the proximity of PCB ring nitrogen atoms and
      functionally relevant H2 O molecules was also determined. Our study demonstrates
      the value of DNP in biological solid-state MAS NMR spectroscopy.

PMID- 27879036
TI  - fMRI single trial discovery of spatio-temporal brain activity patterns.
AB  - There is growing interest in the description of short-lived patterns in the
      spatiotemporal cortical activity monitored via neuroimaging. Most traditional
      analysis methods, designed to estimate relatively long-term brain dynamics, are
      not always appropriate to capture these patterns. Here we introduce a novel data
      driven approach for detecting short-lived fMRI brain activity patterns.
      Exploiting Density Peak Clustering (Rodriguez and Laio [2014]), our approach
      reveals well localized clusters by identifying and grouping together voxels whose
      time-series are similar, irrespective of their brain location, even when very
      short time windows (~10 volumes) are used. The method, which we call Coherence
      Density Peak Clustering (CDPC), is first tested on simulated data and compared
      with a standard unsupervised approach for fMRI analysis, independent component
      analysis (ICA). CDPC identifies activated voxels with essentially no false
      positives and proves more reliable than ICA, which is troubled by a number of
      false positives comparable to that of true positives. The reliability of the
      method is demonstrated on real fMRI data from a simple motor task, containing
      brief iterations of the same movement. The clusters identified are found in
      regions expected to be involved in the task, and repeat synchronously with the
      paradigm. The methodology proposed is especially suitable for the study of short
      time brain dynamics and single trial experiments, where the event or task of
      interest cannot be repeated for the same subject, as happens, for instance, in
      problem-solving, learning and decision-making. A GUI implementation of our method
      is available for download at https://github.com/micheleallegra/CDPC. Hum Brain
      Mapp 38:1421-1437, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27879037
TI  - Nanomembrane-Based, Thermal-Transport Biosensor for Living Cells.
AB  - Knowledge of materials' thermal-transport properties, conductivity and
      diffusivity, is crucial for several applications within areas of biology,
      material science and engineering. Specifically, a microsized, flexible,
      biologically integrated thermal transport sensor is beneficial to a plethora of
      applications, ranging across plants physiological ecology and thermal imaging and
      treatment of cancerous cells, to thermal dissipation in flexible semiconductors
      and thermoelectrics. Living cells pose extra challenges, due to their small
      volumes and irregular curvilinear shapes. Here a novel approach of simultaneously
      measuring thermal conductivity and diffusivity of different materials and its
      applicability to single cells is demonstrated. This technique is based on
      increasing phonon-boundary-scattering rate in nanomembranes, having extremely low
      flexural rigidities, to induce a considerable spectral dependence of the bandgap
      emission over excitation-laser intensity. It is demonstrated that once in contact
      with organic or inorganic materials, the nanomembranes' emission spectrally shift
      based on the material's thermal diffusivity and conductivity. This NM-based
      technique is further applied to differentiate between different types and
      subtypes of cancer cells, based on their thermal-transport properties. It is
      anticipated that this novel technique to enable an efficient single-cell thermal
      targeting, allow better modeling of cellular thermal distribution and enable
      novel diagnostic techniques based on variations of single-cell thermal-transport
      properties.

PMID- 27879038
TI  - Detecting and avoiding likely false-positive findings - a practical guide.
AB  - Recently there has been a growing concern that many published research findings
      do not hold up in attempts to replicate them. We argue that this problem may
      originate from a culture of 'you can publish if you found a significant effect'.
      This culture creates a systematic bias against the null hypothesis which renders
      meta-analyses questionable and may even lead to a situation where hypotheses
      become difficult to falsify. In order to pinpoint the sources of error and
      possible solutions, we review current scientific practices with regard to their
      effect on the probability of drawing a false-positive conclusion. We explain why
      the proportion of published false-positive findings is expected to increase with
      (i) decreasing sample size, (ii) increasing pursuit of novelty, (iii) various
      forms of multiple testing and researcher flexibility, and (iv) incorrect P
      values, especially due to unaccounted pseudoreplication, i.e. the non
      independence of data points (clustered data). We provide examples showing how
      statistical pitfalls and psychological traps lead to conclusions that are biased
      and unreliable, and we show how these mistakes can be avoided. Ultimately, we
      hope to contribute to a culture of 'you can publish if your study is rigorous'.
      To this end, we highlight promising strategies towards making science more
      objective. Specifically, we enthusiastically encourage scientists to preregister
      their studies (including a priori hypotheses and complete analysis plans), to
      blind observers to treatment groups during data collection and analysis, and
      unconditionally to report all results. Also, we advocate reallocating some
      efforts away from seeking novelty and discovery and towards replicating important
      research findings of one's own and of others for the benefit of the scientific
      community as a whole. We believe these efforts will be aided by a shift in
      evaluation criteria away from the current system which values metrics of 'impact'
      almost exclusively and towards a system which explicitly values indices of
      scientific rigour.

PMID- 27879039
TI  - Stereoselective Carbonyl Olefination with Fluorosulfoximines: Facile Access to Z
      or E Terminal Monofluoroalkenes.
AB  - Terminal monofluoroalkenes are important structural motifs in the design of
      bioactive compounds, such as homeostasis regulators and mechanism-based enzyme
      inhibitors. However, it is difficult to control the stereoselectivity of known
      carbonyl olefination reactions, and olefin metathesis is limited to disubstituted
      terminal monofluoroalkenes. Although sulfoximines have been used extensively in
      organic synthesis, reports on their use in carbonyl olefination reactions have
      not appeared to date. Herein, we report highly stereoselective carbonyl
      monofluoroolefination with a fluorosulfoximine reagent. The potential of this
      method is demonstrated by the synthesis of MDL 72161 and by the late-stage
      monofluoromethylenation of complex molecules, such as haloperidol and steroid
      derivatives.

PMID- 27879040
TI  - Differential expression of cucumber RNA-dependent RNA polymerase 1 genes during
      antiviral defence and resistance.
AB  - RNA-dependent RNA polymerase 1 (RDR1) plays a crucial role in plant defence
      against viruses. In this study, it was observed that cucumber, Cucumis sativus,
      uniquely encodes a small gene family of four RDR1 genes. The cucumber RDR1 genes
      (CsRDR1a, CsRDR1b and duplicated CsRDR1c1/c2) shared 55%-60% homology in their
      encoded amino acid sequences. In healthy cucumber plants, RDR1a and RDR1b
      transcripts were expressed at higher levels than transcripts of RDR1c1/c2, which
      were barely detectable. The expression of all four CsRDR1 genes was induced by
      virus infection, after which the expression level of CsRDR1b increased 10-20-fold
      in several virus-resistant cucumber cultivars and in a broad virus-resistant
      transgenic cucumber line expressing a high level of transgene small RNAs, all
      without alteration in salicylic acid (SA) levels. By comparison, CsRDR1c1/c2
      genes were highly induced (25-1300-fold) in susceptible cucumber cultivars
      infected with RNA or DNA viruses. Inhibition of RDR1c1/c2 expression led to
      increased virus accumulation. Ectopic application of SA induced the expression of
      cucumber RDR1a, RDR1b and RDRc1/c2 genes. A constitutive high level of RDR1b gene
      expression independent of SA was found to be associated with broad virus
      resistance. These findings show that multiple RDR1 genes are involved in virus
      resistance in cucumber and are regulated in a coordinated fashion with different
      expression profiles.

PMID- 27879041
TI  - Cyanine-Anchored Silica Nanochannels for Light-Driven Synergistic Thermo
      Chemotherapy.
AB  - Smart nanoparticles are increasingly important in a variety of applications such
      as cancer therapy. However, it is still a major challenge to develop light
      responsive nanoparticles that can maximize the potency of synergistic thermo
      chemotherapy under light irradiation. Here, spatially confined cyanine-anchored
      silica nanochannels loaded with chemotherapeutic doxorubicin (CS-DOX-NCs) for
      light-driven synergistic cancer therapy are introduced. CS-DOX-NCs possess a J
      type aggregation conformation of cyanine dye within the nanochannels and
      encapsulate doxorubicin through the pi-pi interaction with cyanine dye. Under
      near-infrared light irradiation, CS-DOX-NCs produce the enhanced photothermal
      conversion efficiency through the maximized nonradiative transition of J-type
      Cypate aggregates, trigger the light-driven drug release through the
      destabilization of temperature-sensitive pi-pi interaction, and generate the
      effective intracellular translocation of doxorubicin from the lysosomes to
      cytoplasma through reactive oxygen species-mediated lysosomal disruption, thereby
      causing the potent in vivo hyperthermia and intracellular trafficking of drug
      into cytoplasma at tumors. Moreover, CS-DOX-NCs possess good resistance to
      photobleaching and preferable tumor accumulation, facilitating severe
      photoinduced cell damage, and subsequent synergy between photothermal and
      chemotherapeutic therapy with tumor ablation. These findings provide new insights
      of light-driven nanoparticles for synergistic cancer therapy.

PMID- 27879042
TI  - High antibiotic resistance of Helicobacter pylori and its effect on tailored and
      empiric eradication of the organism in Lower Silesia, Poland.
AB  - BACKGROUND: At present, the resistance to antibiotics is considered the most
      important reason for Helicobacter pylori (HP) eradication failure. The aim of
      this study was to estimate the prevalence of antimicrobial resistance of HP
      strains and to evaluate tailored and empiric therapeutic regimens in patients
      with peptic ulcer disease associated with infection of this microorganism.
      MATERIALS AND METHODS: Between May 2011 and February 2013, 185 consecutive Polish
      patients with at least one positive Helicobacter pylori test (urease test,
      histopathologic examination, and/or culture) underwent eradication therapy. Those
      with positive culture were prescribed a tailored triple regimen, whereas those
      with no culture available received an empiric quadruple concomitant regimen or
      levofloxacin-containing triple therapy. RESULTS: There were no HP strains
      resistant to amoxicillin; however, 56.7% were resistant to metronidazole, 55.2%
      to clarithromycin, and 5.9% to levofloxacin. Dual resistance was detected in
      32.8% of individuals. Tailored and empiric therapies achieve cure rates,
      respectively, 95.5% and 86.6% by intention-to-treat and 95.5% and 91.3% by per
      protocol analysis (P > 0.05). CONCLUSIONS: Antibiotic resistance is notably high
      in Poland currently, but both tailored and empiric therapies can achieve
      acceptable cure rates equal to or higher than 90%.

PMID- 27879043
TI  - Uncovering Key Structural Features of an Enantioselective Peptide-Catalyzed
      Acylation Utilizing Advanced NMR Techniques.
AB  - We report on a detailed NMR spectroscopic study of the catalyst-substrate
      interaction of a highly enantioselective oligopeptide catalyst that is used for
      the kinetic resolution of trans-cycloalkane-1,2-diols via monoacylation. The
      extraordinary selectivity has been rationalized by molecular dynamics as well as
      density functional theory (DFT) computations. Herein we describe the
      conformational analysis of the organocatalyst studied by a combination of nuclear
      Overhauser effect (NOE) and residual dipolar coupling (RDC)-based methods that
      resulted in an ensemble of four final conformers. To corroborate the proposed
      mechanism, we also investigated the catalyst in mixtures with both trans
      cyclohexane-1,2-diol enantiomers separately, using advanced NMR methods such as
      T1 relaxation time and diffusion-ordered spectroscopy (DOSY) measurements to
      probe molecular aggregation. We determined intramolecular distance changes within
      the catalyst after diol addition from quantitative NOE data. Finally, we
      developed a pure shift EASY ROESY experiment using PSYCHE homodecoupling to
      directly observe intermolecular NOE contacts between the trans-1,2-diol and the
      cyclohexyl moiety of the catalyst hidden by spectral overlap in conventional
      spectra. All experimental NMR data support the results proposed by earlier
      computations including the proposed key role of dispersion interaction.

PMID- 27879045
TI  - Metal-Free Enantioselective Oxidative Arylation of Alkenes: Hypervalent-Iodine
      Promoted Oxidative C-C Bond Formation.
AB  - The enantioselective oxyarylation of (E)-6-aryl-1-silyloxylhex-3-ene was achieved
      using a lactate-based chiral hypervalent iodine(III) reagent in the presence of
      boron trifluoride diethyl etherate. The silyl ether promotes the oxidative
      cyclization, and enhances the enantioselectivity. In addition, the corresponding
      aminoarylation was achieved.

PMID- 27879044
TI  - Clustering according to urolithin metabotype explains the interindividual
      variability in the improvement of cardiovascular risk biomarkers in overweight
      obese individuals consuming pomegranate: A randomized clinical trial.
AB  - SCOPE: The pomegranate lipid-lowering properties remain controversial, probably
      due to the interindividual variability in polyphenol (ellagitannins) metabolism.
      OBJECTIVE: We aimed at investigating whether the microbially derived ellagitannin
      metabolizing phenotypes, i.e. urolithin metabotypes A, (UM-A), B (UM-B), and 0
      (UM-0), influence the effects of pomegranate extract (PE) consumption on 18
      cardiovascular risk biomarkers in healthy overweight-obese individuals. METHODS
      AND RESULTS: A double-blind, crossover, dose-response, randomized, placebo
      controlled trial was conducted. The study (POMEcardio) consisted of two test
      phases (dose-1 and dose-2, lasting 3 weeks each) and a 3-week washout period
      between each phase. Forty-nine participants (BMI > 27 kg/m2 ) daily consumed one
      (dose-1, 160 mg phenolics/day) or four (dose-2, 640 mg phenolics/day) PE or
      placebo capsules. Notably, UM-B individuals showed the highest baseline
      cardiovascular risk. After dose-2, total cholesterol (-15.5 +/- 3.7%), LDL
      cholesterol (-14.9 +/- 2.1%), small LDL-cholesterol (-47 +/- 7%), non-HDL
      cholesterol (-11.3 +/- 2.5%), apolipoprotein-B (-12 +/- 2.2%), and oxidized LDL
      cholesterol -24 +/- 2.5%) dose dependently decreased (P < 0.05) but only in UM-B
      subjects. These effects were partially correlated with urolithin production and
      the increase in Gordonibacter levels. Three (50%) nonproducers (UM-0) became
      producers following PE consumption. CONCLUSIONS: UM clustering suggests a
      personalized effect of ellagitannin-containing foods and could explain the
      controversial pomegranate benefits. Research on the specific role of urolithins
      and the microbiota associated with each UM is warranted.

PMID- 27879046
TI  - Lithium Germanate (Li2 GeO3 ): A High-Performance Anode Material for Lithium-Ion
      Batteries.
AB  - A simple, cost-effective, and easily scalable molten salt method for the
      preparation of Li2 GeO3 as a new type of high-performance anode for lithium-ion
      batteries is reported. The Li2 GeO3 exhibits a unique porous architecture
      consisting of micrometer-sized clusters (secondary particles) composed of
      numerous nanoparticles (primary particles) and can be used directly without
      further carbon coating which is a common exercise for most electrode materials.
      The new anode displays superior cycling stability with a retained charge capacity
      of 725 mAh g-1 after 300 cycles at 50 mA g-1 . The electrode also offers
      excellent rate capability with a capacity recovery of 810 mAh g-1 (94 %
      retention) after 35 cycles of ascending steps of current in the range of 25-800
      mA g-1 and finally back to 25 mA g-1 . This work emphasizes the importance of
      exploring new electrode materials without carbon coating as carbon-coated
      materials demonstrate several drawbacks in full devices. Therefore, this study
      provides a method and a new type of anode with high reversibility and long cycle
      stability.

PMID- 27879047
TI  - 2-Substituted dATP Derivatives as Building Blocks for Polymerase-Catalyzed
      Synthesis of DNA Modified in the Minor Groove.
AB  - 2'-Deoxyadenosine triphosphate (dATP) derivatives bearing diverse substituents
      (Cl, NH2 , CH3 , vinyl, ethynyl, and phenyl) at position 2 were prepared and
      tested as substrates for DNA polymerases. The 2-phenyl-dATP was not a substrate
      for DNA polymerases, but the dATPs bearing smaller substituents were good
      substrates in primer-extension experiments, producing DNA substituted in the
      minor groove. The vinyl-modified DNA was applied in thiol-ene addition and the
      ethynyl-modified DNA was applied in a CuAAC click reaction to form DNA labelled
      with fluorescent dyes in the minor groove.

PMID- 27879049
TI  - Double-Helix Structure in Carrageenan-Metal Hydrogels: A General Approach to
      Porous Metal Sulfides/Carbon Aerogels with Excellent Sodium-Ion Storage.
AB  - The metal sulfide-carbon nanocomposite is a new class of anode material for
      sodium ion batteries, but its development is restricted by its relative poor rate
      ability and cyclic stability. Herein, we report the use of double-helix structure
      of carrageenan-metal hydrogels for the synthesis of 3D metal sulfide (Mx Sy )
      nanostructure/carbon aerogels (CAs) for high-performance sodium-ion storage. The
      method is unique, and can be used to make multiple Mx Sy /CAs (such as FeS/CA,
      Co9 S8 /CA, Ni3 S4 /CA, CuS/CA, ZnS/CA, and CdS/CA) with ultra-small
      nanoparticles and hierarchical porous structure by pyrolyzing the carrageenan
      metal hydrogels. The as-prepared FeS/CA exhibits a high reversible capacity and
      excellent cycling stability (280 mA h-1 at 0.5 A g-1 over 200 cycles) and rate
      performance (222 mA h-1 at 5 A g-1 ) when used as the anode material for sodium
      ion batteries. The work shows the value of biomass-derived metal sulfide-carbon
      heterostuctures in sodium-ion storage.

PMID- 27879048
TI  - Coordinated protein co-expression in plants by harnessing the synergy between an
      intein and a viral 2A peptide.
AB  - A novel approach is developed for coordinated expression of multiple proteins
      from a single transgene in plants. An Ssp DnaE mini-intein variant engineered for
      hyper-N-terminal autocleavage is covalently linked to the foot-and-mouth disease
      virus 2A (F2A) peptide with unique ribosome skipping property, via a peptide
      linker, to create an 'IntF2A' self-excising fusion protein domain. This IntF2A
      domain acts, in cis, to direct highly effective release of its flanking proteins
      of interest (POIs) from a 'polyprotein' precursor in plants. This is successfully
      demonstrated in stably transformed cultured tobacco cells as well as in different
      organs of transgenic tobacco plants. Highly efficient polyprotein processing
      mediated by the IntF2A domain was also demonstrated in lettuce and Nicotiana
      benthamiana based on transient expression. Protein constituents released from the
      polyprotein precursor displayed proper function and accumulated at similar levels
      inside the cells. Importantly, no C-terminal F2A extension remains on the
      released POIs. We demonstrated co-expression of as many as three proteins in
      plants without compromising expression levels when compared with those using
      single-protein vectors. Accurate differential cellular targeting of released POIs
      is also achieved. In addition, we succeeded in expressing a fully assembled and
      functional chimeric anti-His Tag antibody in N. benthamiana leaves. The IntF2A
      based polyprotein transgene system overcomes key impediments of existing
      strategies for multiprotein co-expression in plants, which is particularly
      important for gene/trait stacking.

PMID- 27879050
TI  - Structural studies of protein arginine methyltransferase 2 reveal its
      interactions with potential substrates and inhibitors.
AB  - : PRMT2 is the less-characterized member of the protein arginine
      methyltransferase family in terms of structure, activity, and cellular functions.
      PRMT2 is a modular protein containing a catalytic Ado-Met-binding domain and
      unique Src homology 3 domain that binds proteins with proline-rich motifs. PRMT2
      is involved in a variety of cellular processes and has diverse roles in
      transcriptional regulation through different mechanisms depending on its binding
      partners. PRMT2 has been demonstrated to have weak methyltransferase activity on
      a histone H4 substrate, but its optimal substrates have not yet been identified.
      To obtain insights into the function and activity of PRMT2, we solve several
      crystal structures of PRMT2 from two homologs (zebrafish and mouse) in complex
      with either the methylation product S-adenosyl-L-homocysteine or other compounds
      including the first synthetic PRMT2 inhibitor (Cp1) studied so far. We reveal
      that the N-terminal-containing SH3 module is disordered in the full-length
      crystal structures, and highlights idiosyncratic features of the PRMT2 active
      site. We identify a new nonhistone protein substrate belonging to the serine
      /arginine-rich protein family which interacts with PRMT2 and we characterize six
      methylation sites by mass spectrometry. To better understand structural basis for
      Cp1 binding, we also solve the structure of the complex PRMT4:Cp1. We compare the
      inhibitor-protein interactions occurring in the PRMT2 and PRMT4 complex crystal
      structures and show that this compound inhibits efficiently PRMT2. These results
      are a first step toward a better understanding of PRMT2 substrate recognition and
      may accelerate the development of structure-based drug design of PRMT2
      inhibitors. DATABASE: All coordinates and structure factors have been deposited
      in the Protein Data Bank: zPRMT21-408 -SFG = 5g02; zPRMT273-408 -SAH = 5fub;
      mPRMT21-445 -SAH = 5ful; mPRMT21-445 -Cp1 = 5fwa, mCARM1130-487 -Cp1 = 5k8v.

PMID- 27879051
TI  - Vascular endothelial growth factor and apelin in plasma of patients with
      retinopathy of prematurity.

PMID- 27879052
TI  - Genotype and Phenotype in an unusual form of Laurence-Moon-Bardet-Biedl syndrome.

PMID- 27879054
TI  - Spontaneous resolution of bilateral central retinal vein occlusion with cystoid
      macular oedema during pregnancy.

PMID- 27879053
TI  - N-Arylsulfonyl Indolines as Retinoic Acid Receptor-Related Orphan Receptor gamma
      (RORgamma) Agonists.
AB  - The nuclear retinoic acid receptor-related orphan receptor gamma (RORgamma;
      NR1F3) is a key regulator of inflammatory gene programs involved in T helper 17
      (TH 17) cell proliferation. As such, synthetic small-molecule repressors (inverse
      agonists) targeting RORgamma have been extensively studied for their potential as
      therapeutic agents for various autoimmune diseases. Alternatively, enhancing TH
      17 cell proliferation through activation (agonism) of RORgamma may boost an
      immune response, thereby offering a potentially new approach in cancer
      immunotherapy. Herein we describe the development of N-arylsulfonyl indolines as
      RORgamma agonists. Structure-activity studies reveal a critical linker region in
      these molecules as the major determinant for agonism. Hydrogen/deuterium exchange
      coupled to mass spectrometry (HDX-MS) analysis of RORgamma-ligand complexes help
      rationalize the observed results.

PMID- 27879055
TI  - Combining field-amplified sample stacking with moving reaction boundary
      electrophoresis on a paper chip for the preconcentration and separation of metal
      ions.
AB  - A common drawback of paper-based separation devices is their poor detection
      limit. In this study, we combined field-amplified sample stacking with moving
      reaction boundary electrophoresis on a paper chip with six array channels for the
      parallel separation and concentration of multiple samples. With a new hyphenated
      technique, the brown I2 from the Fe3+ /I- oxidation-reduction reaction emerged
      near the boundary between the dilute ethylene diamine tetraacetic acid and
      potassium iodide and highly concentrated KCl solutions. For the separation and
      concentration of three components, Cr3+ , Cu2+ , and Fe3+ , the Fe3+ detection
      limit was improved at least 266-fold by comparing the hyphenated technique with
      moving reaction boundary electrophoresis. The detection limit of Fe3+ was found
      to be as low as 0.34 ng (20 MUM) on the paper chip. We also demonstrated the
      analysis of a real sample of four metal ions, with detection limits as follows:
      0.16 MUg Cr3+ , 1.5 MUg Ni2+ , 0.64 MUg Cu2+ , and 1.5 MUg Co2+ . The synergy of
      field-amplified sample stacking and moving reaction boundary electrophoresis in
      the micron paper-based array channels dramatically improved the detection limit
      and throughput of paper-based electrophoresis.

PMID- 27879057
TI  - Direct visualization of aqueous tear secretion from lacrimal gland.
AB  - PURPOSE: To introduce a new method for direct observation of tear secretion from
      the palpebral lobes of the main lacrimal glands and Wolfring glands using
      fluorescein dye. METHODS: Twenty-six patients with dry eye and 26 healthy
      subjects were included in the study. Fluorescein was applied to the conjunctiva
      overlaying the palpebral lobe of the main lacrimal glands. Under cobalt blue
      light, we captured tear secretion from the glands in movies. We compared the
      number of excretory openings, the location and tear flow rate between the dry eye
      and healthy-subject groups. To observe tear secretion from the Wolfring glands,
      we everted the upper lids and applied fluorescein dye to the upper margin of the
      tarsus. RESULTS: Mean number of excretory openings on the palpebral lobe was 2.5
      in the dry eye group and 3.4 in the healthy-subject group (p = 0.031). Most of
      the openings were observed at the ridge, the most protruding portion of the
      palpebral lobe. Mean flow rate from the palpebral lobe was 0.45 MUl/min in the
      dry eye group and 0.91 MUl/min in the healthy-subject group (p = 0.046). Mean
      flow rate from the Wolfring glands was 0.007 MUl/min in the dry eye group and
      0.009 MUl/min in the healthy-subject group (p = 0.615). CONCLUSION: This
      visualization method allowed us to directly observe tear secretion from the
      palpebral lobe of the main lacrimal glands and Wolfring glands, and to
      quantitatively measure the tear flow rate from the lacrimal glands.

PMID- 27879056
TI  - In Vitro Drug and Gene Delivery Using Random Cationic Copolymers Forming Stable
      and pH-Sensitive Polymersomes.
AB  - Stimuli-sensitive polymeric vesicles or polymersomes as self-assembled colloidal
      nanocarriers have received paramount importance for their integral role as
      delivery system for therapeutics and biotherapeutics. This work describes
      spontaneous polymersome formation at pH 7, as evidenced by surface tension,
      steady state fluorescence, dynamic light scattering, and microscopic studies, by
      three hydrophilic random cationic copolymers synthesized using N,N
      (dimethylamino)ethyl methacrylate (DMAEM) and methoxy poly(ethylene glycol)
      monomethacrylate in different mole ratios. The results suggest that methoxy
      poly(ethylene glycol) chains constitute the bilayer membrane of the polymersomes
      and DMAEM projects toward water constituting the positively charged surface. The
      polymersomes have been observed to release their encapsulated guest at acidic pH
      as a result of transformation into polymeric micelles. All these highly
      biocompatible cationic polymers show successful gene transfection ability as
      nonviral vector on human cell line with different potential. Thus these polymers
      prove their utility as a potential delivery system for hydrophilic model drug as
      well as genetic material.

PMID- 27879058
TI  - Sinus surgery can improve quality of life, lung infections, and lung function in
      patients with primary ciliary dyskinesia.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous
      in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas
      aeruginosa can infect the lungs. METHODS: We studied the effect of endoscopic
      sinus surgery (ESS) on symptoms of CRS and lower airway infections in PCD
      patients in a prospective single-arm intervention study of ESS with adjuvant
      therapy using nasal irrigation with saline, topical nasal steroids, and 2 weeks
      of systemic antibiotics. Additional treatment with local colistin for 6 months
      was instigated when P. aeruginosa was cultured at ESS. RESULTS: Twenty-four PCD
      patients underwent ESS to search for an infectious focus (n = 10), due to severe
      symptoms of CRS (n = 8), or both (n = 6). Bacteria were cultured from sinus
      samples in 21 patients (88%), and simultaneous sinus and lung colonization with
      identical pathogens were observed in 13 patients (62%). Four patients with
      preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow
      up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12
      months after ESS and we observed a trend toward better lung function after ESS.
      CONCLUSION: We demonstrated an improvement in CRS-related symptoms after ESS and
      adjuvant therapy. In selected PCD patients, the suggested regimen may postpone
      chronic lung infection with P. aeruginosa and stabilize lung function.

PMID- 27879059
TI  - Squash cytology of tanycytic ependymoma: A report of two cases.
AB  - Tanycytic ependymoma is a rare variant of ependymoma which has a predilection for
      the spinal cord. It is a WHO grade II tumour with favourable outcome. Although
      squash cytology of ependymoma is well described, there is sparse literature
      available on squash cytomorphology of tanycytic variant. Here we present two
      cases of squash cytology of tanycytic ependymoma. In the first case the diagnosis
      of tanycytic ependymoma was considered. However, in the second case a diagnosis
      of usual ependymoma was offered. Subsequently histopathology confirmed tanycytic
      nature in both the cases. In this article we discuss the squash cytological
      features of tanycytic ependymoma along with its differential diagnosis. Diagn.
      Cytopathol. 2017;45:270-273. (c) 2016 Wiley Periodicals, Inc.

PMID- 27879061
TI  - Patterned SLIPS for the Formation of Arrays of Biofilm Microclusters with Defined
      Geometries.
AB  - Biofilms represent an immense problem in medicine due to their strong drug
      resistant properties and inherent stress-response activities. Due to the
      inhomogeneous and very complex architectures of large biofilm aggregates, biofilm
      studies often suffer from low reproducibility. In this study, an approach to form
      arrays of homogeneous biofilm microclusters with defined 2D geometries is
      presented. The method is based on the formation of water-infused hydrophilic
      porous polymer areas with precise geometries separated by "slippery" lubricant
      infused porous surface (SLIPS). Due to the SLIPS' biofilm repellent properties,
      multiple identical 3D biofilm clusters are formed in the hydrophilic patches that
      can be used for biofilm screening. Formation of biofilm microcluster arrays of
      different bacterial strains of Pseudomonas aeruginosa on the SLIPS micropatterns
      is investigated. Critical parameters influencing minimal adhesive regions for
      biofilm attachment and minimal SLIPS dimensions to avoid biofilm adhesion are
      studied. The ability to produce arrays of biofilm microclusters with highly
      uniform, well-defined shapes opens an opportunity to study interactions of
      biofilms with various medically relevant factors with a better reproducibility
      and to investigate the complex biofilm architecture, heterogeneity, and
      interactions between biofilm subpopulations.

PMID- 27879060
TI  - Evidence of microbiota dysbiosis in chronic rhinosinusitis.
AB  - BACKGROUND: Despite considerable research, the pathogenesis of chronic
      rhinosinusitis (CRS) remains poorly understood. Potential microbial roles in the
      etiology or progression of CRS have long been hypothesized, yet few specific
      associations have been identified. In this study we investigate associations
      between patterns in resident bacterial communities and clinical variants of CRS.
      METHODS: Bacterial communities were assessed in 94 patients with extensive
      bilateral CRS undergoing endoscopic sinus surgery (ESS) and 29 controls
      undergoing ESS for indications other than CRS. Patients were grouped on the basis
      of phenotypic variants (with or without polyposis) and clinical parameters,
      including asthma and cystic fibrosis. Bacterial communities were characterized
      via 16S rRNA gene amplicon sequencing, and quantified by quantitative polymerase
      chain reaction. RESULTS: Controls and idiopathic CRS subjects tended to be
      dominated by members of the genera Corynebacterium and Staphylococcus, together
      with lower abundances of several other genera, including Streptococcus,
      Moraxella, and Haemophilus. Aberrant (dysbiotic) bacterial assemblages (with
      changes in community membership and structure, reduced diversity, and increased
      bacterial load) and increased inter- and intrasubject variability were more
      common in subjects with comorbidities such as asthma and cystic fibrosis.
      Dysbiotic communities were variably dominated by members of the genera
      Staphylococcus, Streptococcus, Haemophilus, Pseudomonas, Moraxella, or
      Fusobacterium. CONCLUSION: Bacterial community dysbiosis was more apparent than
      specific associations with examined phenotypes or endotypes, and may play a role
      in the pathogenesis or influence the severity of CRS. Reductions in several
      common core bacterial taxa, increased inter- and intrasubject variability,
      reduced bacterial diversity, and increased bacterial load characterized aberrant
      bacterial communities in CRS.

PMID- 27879062
TI  - Preparation of Heteroaromatic (Aryl)iodonium Imides as I-N Bond-Containing
      Hypervalent Iodine.
AB  - Hypervalent iodine(III) compounds containing iodine-nitrogen bonds are very
      attractive amination reagents in organic synthesis. Heteroaromatic (aryl)iodonium
      imides containing a iodine-nitrogen bond and a hypervalent iodine(III) atom were
      prepared from heteroarenes, bis(sulfon)imides and (diacetoxyiodo)arenes under
      mild conditions. These compounds were stable under air and in organic solvents,
      and could be easily purified by precipitation. X-ray crystal structure analysis
      indicated that the structure of N-pivaloyl indolyl(phenyl)iodonium
      bis(tosyl)imides and N-pivaloyl indolyl(2-butoxyphenyl)iodonium bis(tosyl)imides
      was a dimer with a T-shaped geometry at the iodine atom linked to an indole group
      and a bis(tosyl)imide by a monomer unit. Moreover, the use of substituted
      iodoarenes facilitated the purification of some of the heteroaromatic
      (aryl)iodonium imides.

PMID- 27879063
TI  - Carbazole Aminoalcohols Induce Antiproliferation and Apoptosis of Human Tumor
      Cells by Inhibiting Topoisomerase I.
AB  - Novel carbazole aminoalcohols were designed and synthesized as anticancer agents.
      Among them, alkylamine-chain-substituted compounds showed the most promising
      antiproliferative activity, with IC50 values in the single-digit micromolar range
      against two human tumor cell lines. Topoisomerase I (topo I) is likely to be one
      of the targets of these compounds. Results of comet assays and molecular docking
      indicate that the representative compounds may act as topo I poisons, causing
      single-strand DNA damage by stabilizing the topo I-DNA cleavage complex. In
      particular, the most potent compound, 1-(butylamino)-3-(3,6-dichloro-9H-carbazol
      9-yl)propan-2-ol (6), was shown to be able to induce G2 -phase cell-cycle arrest
      and apoptosis in HeLa cells.

PMID- 27879064
TI  - Clear cell carcinoma first suspected in Pap smear. The value of neutrophil
      cannibalism by tumor cells.

PMID- 27879065
TI  - Early diagnosis of intravascular large B-cell lymphoma.

PMID- 27879066
TI  - XXIX. Symposium Augustanum - Jahrestagung der Deutsch-Italienischen Gesellschaft
      fur Dermatologie e. V. in Genua am 27. Mai 2016.

PMID- 27879067
TI  - Ustekinumab in the treatment of palmoplantar pustular psoriasis - a case series
      of nine patients.
AB  - BACKGROUND: Palmoplantar pustular psoriasis is a chronic inflammatory skin
      disease that is associated with considerable impairment in quality of life and
      resilience. Given the lack of approved pharmacological agents for this indication
      and the frequently recalcitrant disease course, therapeutic options are limited.
      PATIENTS AND METHODS: Following unsatisfactory therapeutic attempts with other
      treatment modalities, nine patients (six women; three men) were treated with
      ustekinumab (45 mg in individuals < 100 kg body weight, 90 mg in individuals >
      100 kg) at weeks 0, 4, 12, and 24. Latent tuberculosis was ruled out prior to
      treatment. Regular follow-up was done at week 4 and 12, and every 12 weeks
      thereafter. RESULTS: Average age at the beginning of treatment was 48 years. Four
      patients achieved 75 % improvement in the palmoplantar Psoriasis Area Severity
      Index (PASI). Overall, there was an average improvement in the palmoplantar PASI
      of 71.6 % after 24 weeks. Two patients exhibited complete resolution after 24
      weeks. Besides local injection site reactions and mild infections, no adverse
      effects were observed. CONCLUSIONS: This case series provides further evidence
      for the effectiveness and tolerability of ustekinumab in the treatment of
      palmoplantar pustular psoriasis. Controlled studies and observations in the
      context of patient registries are required to assess long-term efficacy and
      safety as well as the potential therapeutic benefit of intermittent therapy.

PMID- 27879068
TI  - Chronische spontane Urtikaria in Verbindung mit einer primar billiaren
      Cholangitis: ein Fallbericht und Literaturuberblick.

PMID- 27879069
TI  - Einseitig wandernde entzundliche filiforme Rotung an der Fubetasohle.

PMID- 27879070
TI  - Agminated orange papules on the face.

PMID- 27879071
TI  - "Drug-Survival"-Raten und Grunde fur den Abbruch von Systemtherapien bei
      Psoriasis.
AB  - HINTERGRUND UND ZIELE: Mittelschwere bis schwere Psoriasis erfordert haufig eine
      langfristige systemische Behandlung. Die Therapietreue bezuglich eines Medika
      ments (Uberlebensrate, "Drug Survival") reflektiert dessen Wirksamkeit,
      Sicherheit sowie die Zufriedenheit mit der Behandlung und ist ein Indikator fur
      den Therapieerfolg. Das Ziel der vorliegenden Studie was die Ermittlung der "Drug
      Survival"-Raten sowie der Grunde fur den Abbruch einer Behandlung mit
      Fumarsaureestern (fumaric acid esters, FAE), Methotrexat (MTX), Acitretin (ACI),
      Cyclosporin A (CyA), Adalimumab (ADA), Etanercept (ETA), Infliximab (INF) und
      Ustekinumab (UST) bei Patienten mit mittelschwerer bis schwerer Psoriasis.
      PATIENTEN UND METHODEN: Wir fuhrten eine retrospektive Analyse an 373 Patienten
      durch, die im Zeitraum 1/2003-5/2014 insgesamt 696 Behandlungen an einem
      deutschen Universitatsklinikum erhalten hatten. ERGEBNISSE: Die unbereinigte
      Uberlebenswahrscheinlichkeit war fur UST am hochsten, gefolgt von ADA, ETA, INF,
      FAE, MTX, ACI und CyA. In der multivariaten Regressionsanalyse mit FAE als
      Referenz betrug die Hazard Ratio (HR) fur einen Abbruch 0,14 (95 %
      Konfidenzintervall: 0,06-0,35) bei UST, 0,43 (0,26-0,73) bei ADA, 2,11 (1,14
      3,91) bei ACI und 3,26 (1,44-7,39) bei CyA. Das "Drug Survival" von INF war
      langer, wenn es in Kombination mit MTX eingesetzt wurde (HR 2,87; 1,21-6,81).
      Traditionelle systemische Antipsoriatika sowie INF wurden am haufigsten aufgrund
      von Nebenwirkungen abgesetzt; alle anderen Biologika aufgrund ihrer Unwirksamkeit
      fur kutane Psoriasis-Lasionen. SCHLUSSFOLGERUNGEN: "Drug-Survival"-Raten sollten
      bei der Therapieentscheidung berucksichtigt werden, um den Patienten eine
      bestmogliche Langzeitstrategie zu bieten.

PMID- 27879072
TI  - Keratosis lichenoides chronica mit untypischer klinischer Prasentation und
      variblen histopathologischen Merkmalen.

PMID- 27879073
TI  - Systemic sclerosis in a stonemason - an occupational disease?

PMID- 27879075
TI  - Systemische Sklerose nach Tatigkeit als Steinmetz - eine Berufskrankheit?

PMID- 27879074
TI  - S1 guidelines on the diagnosis and treatment of scabies - short version.
AB  - The goals of this German guideline are the improvement of diagnosis and therapy
      of scabies, the implementation of a coordinated action in outbreaks of scabies,
      and the control of this infestation in large migration or refugee flows.Sarcoptes
      scabiei var. hominis is transmitted by direct skin-to-skin contact of sufficient
      duration. The infectivity of female mites when removed from patients does not
      exceed 48 hours at room temperature (21 degrees C) and relative humidity of 40
      80%. The risk of infection rises proportionally to the number of mites on the
      skin and is particularly high in crusted scabies. As elderly persons tend to
      develop crusted scabies due to disease- or medication-related immunosuppression,
      there is an increased risk for outbreaks of scabies at nursing homes and extended
      care facilities. The guideline contains detailed recommendations for management
      of such outbreaks. In refugees the prevalence of scabies is higher than in the
      general population in Germany, but the risk for outbreaks is not high. Scabies
      infestation should be considered when a recent onset of itching is associated
      with eczema and presence of burrows or comma-like papules at predilection sites.
      It is confirmed by dermatoscopic detection of mites or by microscopic
      identification of mites, mite eggs or fecal matter (scybala) from skin
      scrapings.The treatment of choice for common scabies is topical permethrin 5%
      cream applied for 8-12 hours. Permethrin can be considered for off-label use also
      in infants of less than 3 months of age and pregnant women. For this group
      crotamiton is another option, which, besides benzyl benzoate, presents a good
      second line therapy for the other indications. Indications for oral ivermectin,
      which has just been licensed in Germany, include patients with immunosuppression,
      severe dermatitis, and low adherence.Crusted scabies is preferentially treated by
      a combination of topical permethrin and oral ivermectin. Affected patients should
      be isolated, and all contact persons should be treated. The guideline contains
      lists for additional measures, including possible treatment of contact persons,
      clothes, linen and other possibly infested articles.

PMID- 27879077
TI  - Nachruf.

PMID- 27879076
TI  - Drug survival rates and reasons for drug discontinuation in psoriasis.
AB  - BACKGROUND AND OBJECTIVES: Moderate-to-severe psoriasis frequently requires long
      term systemic therapy. Reflecting efficacy, safety, and treatment satisfaction,
      drug survival is an indicator of therapeutic success. The objective of the
      present study was to assess drug survival rates and reasons for discontinuation
      of fumaric acid esters (FAE), methotrexate (MTX), acitretin (ACI), cyclosporine A
      (CyA), adalimumab (ADA), etanercept (ETA), infliximab (INF), and ustekinumab
      (UST) in patients with moderate-to-severe psoriasis. PATIENTS AND METHODS: We
      performed a retrospective analysis of 373 patients who had received a total of
      696 treatment courses at a German university hospital in the period 1/2003
      5/2014. RESULTS: The crude probability of survival was highest for UST, followed
      by ADA, ETA, INF, FAE, MTX, ACI, and CyA. In multivariate regression analysis
      using FAE as reference, hazard ratios (HR) for discontinuation were 0.14 (95 %
      confidence interval: 0.06-0.35) for UST, 0.43 (0.26-0.73) for ADA, 2.11 (1.14
      3.91) for ACI, and 3.26 (1.44-7.39) for CyA. INF showed longer survival when
      combined with MTX (HR 2.87, 1.21-6.81). Traditional systemic antipsoriatic agents
      as well as INF were most frequently discontinued due to adverse events; all other
      biologics, due to inefficacy with respect to cutaneous lesions. CONCLUSIONS: Drug
      survival rates should be integrated into therapeutic decisions in order to
      provide patients with an optimal long-term strategy.

PMID- 27879078
TI  - Multiple basal cell carcinomas arising in an epidermal nevus.

PMID- 27879079
TI  - Chronic spontaneous urticaria associated with primary biliary cirrhosis: a case
      report and literature review.

PMID- 27879080
TI  - S1-Leitlinie zur Diagnostik und Therapie der Skabies - Kurzfassung.

PMID- 27879081
TI  - Hemophagocytic lymphohistiocytosis associated with subcutaneous panniculitis-like
      T-cell lymphoma.

PMID- 27879082
TI  - Potenzielle Arzneimittelwechsel-wirkungen und unerwunschte Arzneimittelwirkungen
      bei stationaren dermatologischen Patienten.
AB  - ZIELE: Informationen zur Haufigkeit von Arzneimittelwechselwirkungen und
      unerwunschten Arzneimittelwirkungen zu prasentieren und Hilfestellung zu leisten,
      wie diese wichtigen Probleme in der pharmakologischen Behandlung stationarer
      dermatologischer Patienten minimiert werden konnen. PATIENTEN UND METHODEN: Die
      Medikation von 1 099 stationaren dermatologischen Patienten wurde retrospektiv
      mittels einer Internet-basierten Software fur Medikamenteninteraktionen
      (Diagnosia(r) Check) auf Arzneimittelwechselwirkungen und unerwunschte
      Arzneimittelwirkungen analysiert. ERGEBNISSE: Wir beschreiben eine
      Gesamthaufigkeit relevanter Arzneimittelwechselwirkungen von 51,7 % mit
      durchschnittlich 3,2 Interaktionen pro betroffenem stationaren Patienten.
      Arzneimittelkombinationen, die gemieden werden sollten, wurden bei 5,7 % der
      Studienpopulation festgestellt. Der wichtigste Risikofaktor war die Gesamtzahl
      der verabreichten Medikamente. Die Arzneimittelgruppen, die bei der Mehrzahl der
      Wechselwirkungen beteiligt waren, waren Analgetika, Herz-Kreislauf-Medikamente
      und gerinnungshemmende Medikamente sowie Antidepressiva. Das Risiko unerwunschte
      Arzneimittelwirkungen auszubilden wurde bei 53,1 % der stationaren Patienten als
      "hoch" eingestuft. Die funf wichtigsten unerwunschten Nebenwirkungen in dieser
      Patientengruppe waren Blutungen, Obstipation, anticholinerge Effekte, Sedierung
      und orthostatische Effekte. SCHLUSSFOLGERUNGEN: Potenzielle
      Arzneimittelwechselwirkungen sowie unerwunschte Arzneimittelwirkungen sind bei
      stationaren dermatologischen Patienten alarmierend haufig. Bei jedem zweiten
      Patienten besteht die Gefahr, derartige Wechselwirkungen oder unerwunschte
      Nebenwirkungen zu erleiden und jeder zwanzigste Patient erhalt eine
      Arzneimittelkombination, die nicht verabreicht werden sollte. Erhohte Wachsamkeit
      ist erforderlich, um die gefahrdeten Patienten zu erkennen.

PMID- 27879083
TI  - Ustekinumab in der Therapie der Pustulosis palmoplantaris - Eine Fallserie mit
      neun Patienten.
AB  - HINTERGRUND: Die Pustulosis palmoplantaris ist eine chronisch entzundliche
      Hauterkrankung, die mit bedeutenden Einschrankungen der Lebensqualitat und der
      Belastbarkeit einhergeht. Aufgrund von Zulassungsbeschrankungen und einem haufig
      therapierefraktaren Verlauf sind die Behandlungsmoglichkeiten limitiert.
      PATIENTEN UND METHODIK: Nach zuvor frustranen Therapien erhielten 9 Patienten mit
      Pustulosis palmoplantaris nach Ausschluss einer latenten Tuberkulose Ustekinumab
      (45 mg Ustekinumab bei < 100 kg Korpergewicht [KG], 90 mg Ustekinumab > 100 kg
      KG) in Woche 0, 4, 12 und 24. Regulare Visiten erfolgten nach 4 und 12 Wochen, im
      weiteren Verlauf alle 12 Wochen. ERGEBNISSE: Das Durchschnittsalter bei
      Therapiebeginn betrug 48 Jahre. Drei Patienten waren mannlich. Bei n  =  4
      Patienten (44,4 %) wurde eine Verbesserung um 75 % des Palmoplantar-Psoriasis
      Area-Severity-Index (PPPASI) erreicht. Insgesamt verbesserte sich der PPPASI nach
      24 Wochen durchschnittlich um 71,6 %. Eine komplette Abheilung zeigte sich bei n 
      =  2 Patienten nach 24 Wochen. Bis auf lokale Injektionsreaktionen und leichte
      Infekte wurden keine unerwunschten Wirkungen beobachtet. SCHLUSSFOLGERUNGEN: Die
      Fallserie ist ein weiterer Beleg fur die Wirksamkeit und Vertraglichkeit von
      Ustekinumab in der Therapie der Pustulosis palmoplantaris. Zur Beurteilung der
      Langzeitwirkung und -sicherheit sowie der Wirksamkeit einer intermittierenden
      Therapie sind kontrollierte Studiendaten sowie Beobachtungen im Rahmen von
      Patientenregistern notwendig.

PMID- 27879084
TI  - Topical preparations and their use in dermatology.
AB  - The challenges of everyday clinical routine require dermatologists to have a
      basic knowledge of the composition of topical preparations as well as the
      regulatory background associated with their prescription. Proper selection,
      prescription, and application of topical preparations, depending on the
      respective indication, are key to professional and responsible medical practice.
      Problems commonly arise with respect to regulatory classifications (medicinal
      products, medical devices, or cosmetics), eligibility for reimbursement by the
      statutory health insurances (GKV), and insufficient declaration of vehicle
      systems. Apart from selecting the appropriate active substance and its proper
      concentration, choosing a suitable pharmaceutical (galenic) formulation - and
      thus utilizing the intrinsic effects thereof - is pivotal in enhancing the
      intended therapeutic effects. When prescribing individual formulations,
      dermatologists should, to the greatest extent possible, always resort to
      standardized extemporaneous preparations. Given the multitude of potential
      ingredients available for pharmaceutical formulations as well as the complexity
      resulting therefrom, arbitrary changes in quality or quantity of individual
      components are associated with a high risk of instability, thus jeopardizing
      safety and the rationale behind any given formulation. Optimal use of topical
      preparations also requires basic knowledge in pharmacokinetics as well as
      evidence-based treatment planning.

PMID- 27879087
TI  - Dr. Kurt und Eva Herrmann-Stipendium in Hohe von 10 000 Euro fur junge
      Dermatologinnen/Dermatologen.

PMID- 27879085
TI  - Potential drug-drug interactions and adverse drug reactions in dermatological
      inpatients.
AB  - OBJECTIVES: To present information on the frequency of drug-drug interactions and
      adverse drug reactions, and to provide assistance on how to minimize these major
      problems in the pharmacological treatment of dermatological inpatients. PATIENTS
      AND METHODS: The medications given to 1,099 dermatological inpatients were
      retrospectively analyzed for drug-drug interactions and adverse drug reactions
      using web-based drug interaction software (Diagnosia(r) Check). RESULTS: We
      report an overall frequency of relevant drug-drug interactions of 51.7 %, with an
      average of 3.2 interactions per affected inpatient. Drug combinations that should
      have been avoided were found in 5.7 % of the study population. Total drug count
      was the most important risk factor. Drug groups involved in the majority of
      interactions were analgesics, cardiovascular and antithrombotic agents, as well
      as antidepressants. The risk of developing adverse drug reactions was rated as
      "high" in 53.1 % of inpatients. The top five adverse reactions in this patient
      group were bleeding, constipation, anticholinergic effects, sedation, and
      orthostatic effects. CONCLUSIONS: Potential drug-drug interactions as well as
      adverse drug reactions are alarmingly common in dermatological inpatients. Every
      other patient is at risk of experiencing such interactions or adverse reactions,
      and every twentieth patient receives a drug combination that should not be
      administered. Increased alertness is a must in order to identify patients at
      risk.

PMID- 27879088
TI  - Aggregierte orangefarbene Papeln im Gesicht.

PMID- 27879089
TI  - Keratosis lichenoides chronica with an atypical clinical presentation and
      variable histopathological features.

PMID- 27879090
TI  - Hamophagozytotisches Syndrom bei subkutanem pannikulitisartigen T-Zell-Lymphom.

PMID- 27879091
TI  - Kongresskalender 2016.

PMID- 27879092
TI  - Unilateral migratory linear plantar erythema.

PMID- 27879094
TI  - Es hort doch jeder nur, was er versteht.

PMID- 27879093
TI  - Prognostic value of the area and density of lymphatic vessels in cutaneous
      squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Cutaneous squamous cell carcinoma (SCC) is known for
      its capacity to metastasize via lymphatic vessels. In recent studies, the level
      of lymphangiogenesis has been reported as a potential prognostic factor for
      several skin tumors. The aim of this study was to quantify lymphangiogenesis in
      SCC using either computer-assisted image analysis or the Chalkley count
      technique. Vascular parameters were evaluated and compared with respect to their
      predictive power for tumor metastasis. PATIENT AND METHODS: In this case-control
      study, clinical and histological data of 15 metastatic and 15 nonmetastatic SCC
      patients were retrospectively analyzed. SCC samples were immunostained for the
      lymphatic endothelial marker D2-40 and the panvascular marker CD31, and analyzed
      using computer-assisted morphometric image analyses within hot spots as well as
      the digitalized Chalkley counting method. RESULTS: Lymphatic vessel density,
      relative lymphatic vessel area, and lymphatic Chalkley count were significantly
      elevated in metastatic SCC. Tumor thickness was significantly higher in
      metastatic SCC, and had the highest predictive power for metastatic disease.
      Tumor thickness was a significant predictor of lymphangiogenic parameters.
      CONCLUSIONS: Lymphangiogenesis is elevated in metastatic SCC but its extent is
      influenced by tumor thickness. Tumor thickness remains the most reliable
      predictive factor for metastatic disease.

PMID- 27879095
TI  - Fruhzeitige Diagnose des intravaskularen grobetazelligen B-Zell-Lymphoms.

PMID- 27879098
TI  - Auftreten multipler Basalzellkarzinome in einem epidermalen Navus.

PMID- 27879099
TI  - Verleihung der Goldmedaille der Osterreichischen Gesellschaft fur Dermatologie
      und Venerologie an Otto Braun-Falco.

PMID- 27879096
TI  - Compression therapy in patients with venous leg ulcers.
AB  - Wund-D.A.CH. is the umbrella organization of the various wound care societies in
      German-speaking countries. The present consensus paper on practical aspects
      pertinent to compression therapy in patients with venous leg ulcers was developed
      by experts from Germany, Austria, and Switzerland. In Europe, venous leg ulcers
      rank among the most common causes of chronic wounds. Apart from conservative and
      interventional wound and vein treatment, compression therapy represents the basis
      of all other therapeutic strategies. To that end, there are currently a wide
      variety of materials and systems available. While especially short-stretch
      bandages or multicomponent systems should be used in the initial decongestion
      phase, ulcer stocking systems are recommended for the subsequent maintenance
      phase. Another - to date, far less common - alternative are adaptive Velcro
      bandage systems. Medical compression stockings have proven particularly
      beneficial in the prevention of ulcer recurrence. The large number of treatment
      options currently available enables therapists to develop therapeutic concepts
      geared towards their patients' individual needs and abilities, thus resulting in
      good acceptance and adherence. Compression therapy plays a crucial role in the
      treatment of patients with venous leg ulcers. In recent years, a number of
      different treatment options have become available, their use and application
      differing among German-speaking countries. The present expert consensus is
      therefore meant to outline concrete recommendations for routine implementation of
      compression therapy in patients with venous leg ulcers.

PMID- 27879100
TI  - Topika und deren Einsatz in der Dermatologie.
AB  - Grundkenntnisse zur Zusammensetzung und den regulatorischen Hintergrunden von
      Topika gehoren zu den alltaglich benotigten Herausforderungen dermatologisch
      arztlichen Handelns. Ein professioneller und indikationsgerechter Umgang bei der
      Auswahl, Verordnung und Anwendung topischer Praparate ist somit Voraussetzung fur
      eine verantwortungsvolle facharztliche Tatigkeit. Dabei bereiten die
      regulatorische Zuordnung (Arzneimittel, Medizinprodukt, Kosmetikum), die
      Feststellung der Erstattungsfahigkeit durch die GKV und die unzureichende
      Kennzeichnung des Vehikelsystems einzelner Praparate nicht selten Probleme.
      Bestreben sollte es sein, neben der Wahl des geeigneten Wirkstoffs und der
      geeigneten Konzentration ein an die Indikation der Therapie angepasstes
      galenisches System auszuwahlen, um dessen Eigenwirkung fur den therapeutischen
      Effekt nutzen zu konnen. Bei der Verschreibung von Rezepturarzneimitteln sollte
      nach Moglichkeit immer auf eine standardisierte Rezeptur (Magistralrezeptur)
      zuruckgegriffen werden. Durch die Vielzahl der moglichen Inhaltsstoffe und der
      sich daraus ergebenden Komplexitat eines galenischen Systems ist eine
      willkurliche Manipulation durch qualitative oder quantitative Veranderungen
      einzelner Komponenten mit hohen Risiken fur eine Instabilitat und damit fur
      Sicherheit und Sinnhaftigkeit verbunden. Eine optimierte Anwendung von Topika
      setzt zudem Grundlagenkenntnisse zur Pharmakokinetik und zur evidenzbasierten
      Therapieplanung voraus.

PMID- 27879101
TI  - Kompressionstherapie bei Patienten mit Ulcus cruris venosum.
AB  - Wund-D.A.CH. ist der Dachverband deutschsprachiger Fachgesellschaften, die sich
      mit den Thematiken der Wundbehandlung beschaftigen. Experten verschiedener
      Fachgesellschaften aus Deutschland, Osterreich und der Schweiz haben nun einen
      aktuellen Konsens der Kompressionstherapie fur Patienten mit Ulcus cruris venosum
      erstellt. In Europa ist das Ulcus cruris venosum eine der haufigsten Ursachen fur
      chronische Wunden. Neben der konservativen und interventionellen Wund- und
      Venentherapie, ist die Kompressionstherapie die Basis der Behandlungsstrategien.
      Die Kompressionstherapie kann heute mit sehr unterschiedlichen Materialien und
      Systemen durchgefuhrt werden. Wahrend in der Entstauungsphase insbesondere
      Verbande mit Kurzzugbinden oder Mehrkomponentensysteme zur Anwendung kommen, sind
      es anschliebetaend uberwiegend Ulkus-Strumpfsysteme. Eine weitere, bislang wenig
      verbreitete Alternative sind adaptive Kompressionsbandagen. Insbesondere fur die
      Rezidivprophylaxe werden medizinische Kompressionsstrumpfe empfohlen. Durch die
      Vielzahl der heute zur Verfugung stehenden Behandlungsoptionen, kann fur nahezu
      alle Patienten ein Konzept entwickelt werden, dass sich an den individuellen
      Bedurfnissen und Fahigkeiten orientiert und daher auch akzeptiert und
      durchgefuhrt wird. Die Kompressionstherapie ist fur die Behandlung von Patienten
      mit Ulcus cruris venosum essentiell. In den letzten Jahren sind viele
      verschiedene Therapieoptionen verfugbar, die in den deutschsprachigen Landern
      unterschiedlich angewendet oder durchgefuhrt werden. Daher soll dieser
      Expertenkonsens dazu beitragen, konkrete Empfehlungen fur die praktische
      Durchfuhrung der Kompressionstherapie von Patienten mit Ulcus cruris venosum
      darzustellen.

PMID- 27879102
TI  - Prognostischer Wert der Flache und Dichte von Lymphgefabetaen bei kutanem
      Plattenepithelkarzinom.
AB  - HINTERGRUND UND ZIELE: Kutane Plattenepithelkarzinome (SCC) sind bekannt fur ihre
      Fahigkeit, uber Lymphgefabetae zu metastasieren. In neueren Studien wird das
      Ausmabeta der Lymphangiogenese als moglicher prognostischer Faktor bei einigen
      Hauttumoren genannt. Ziel dieser Studie war die Quantifizierung der
      Lymphangiogenese bei SCC entweder durch computergestutzte Bildanalyse oder
      mithilfe der Zahlmethode nach Chalkley. Gefabetaparameter wurden im Hinblick auf
      ihre Vorhersagekraft fur die Bildung von Tumormetastasen beurteilt und
      verglichen. PATIENTEN UND METHODEN: In dieser Fallkontrollstudie wurden die
      klinischen und histologischen Daten von jeweils 15 SCC-Patienten mit bzw. ohne
      Metastasen retrospektiv analysiert. In den SCC-Proben wurde der fur das
      Lymphendothel spezifische Marker D2-40 und der pan-vaskulare Marker CD31
      immunhistochemisch angefarbt und durch computergestutzte morphometrische
      Bildanalyse in Hotspots sowie mithilfe der digitalisierten Zahlmethode nach
      Chalkley analysiert. ERGEBNISSE: Die Dichte von Lymphgefabetaen, die relative
      Lymphgefabetaflache und die mit der Chalkley-Methode ermittelte Zahl an
      Lymphgefabetaen (Chalkley-Count) waren bei metastasierten SCC signifikant erhoht.
      Die Tumordicke war bei metastasierten SCC signifikant hoher und besabeta die
      hochste Vorhersagekraft fur eine Metastasierung. Die Tumordicke war ein
      signifikanter Pradiktor fur Lymphangiogeneseparameter. SCHLUSSFOLGERUNGEN: Die
      Lymphangiogenese ist bei metastasierten SCC erhoht, doch ihr Ausmabeta wird von
      der Tumordicke beeinflusst. Die Tumordicke bildet weiterhin den zuverlassigsten
      pradiktiven Faktor fur die Metastasierung.

PMID- 27879103
TI  - Nagelbefall kann bei Patienten mit Psoriasis auf eine Enthesiopathie hinweisen.
AB  - HINTERGRUND: Obwohl subklinische Enthesiopathie ein gut etabliertes
      diagnostisches Merkmal der Psoriasisarthritis (PsA) ist, wird sie haufig
      ubersehen, da viele Patienten asymptomatisch sind. Gabe es klinische Hinweise auf
      das Vorliegen einer Enthesiopathie, wurde dies den Klinikern die Moglichkeit
      eroffnen, eine PsA fruhzeitig zu diagnostizieren. MATERIAL UND METHODEN: Es wurde
      eine monozentrische prospektive Studie mit insgesamt 90 Psoriasis-Patienten
      durchgefuhrt, um mittels Ultraschall das Vorliegen von Enthesenanomalien zu
      untersuchen und eine Korrelation mit dem Befall der Nagel festzustellen.
      ERGEBNISSE: Enthesenanomalien wurden bei 23 Patienten (25,5 %) gefunden, von
      denen 19 (82,6 %) Nagelbefall aufwiesen. Bei 4 Patienten waren die Nagel nicht
      betroffen. Enthesiopathie lag bei 31,1 % (19/61) der Patienten mit Onychopathie
      vor, von den Patienten ohne Nagelbefall litten nur 13,8 % (4/29) an
      Enthesiopathie (p = 0,07). Zwischen dem Target-NAPSI-Score und dem Vorliegen
      einer Enthesiopathie bestand eine signifikante Korrelation. Eine signifikante
      Korrelation bestand daruber hinaus auch zwischen dem Vorliegen einer
      Enthesiopathie und der Anzahl der betroffenen Nagel (p = 0,035).
      SCHLUSSFOLGERUNGEN: Klinische Belege fur eine Onychopathie konnen der Schlussel
      fur die fruhe Diagnose einer Enthesiopathie bei Psoriasis-Patienten sein.

PMID- 27879104
TI  - Multiplayer games and HIV transmission via casual encounters.
AB  - Population transmission models have been helpful in studying the spread of HIV.
      They assess changes made at the population level for different intervention
      strategies. To further understand how individual changes affect the population as
      a whole, game-theoretical models are used to quantify the decision-making
      process. Investigating multiplayer nonlinear games that model HIV transmission
      represents a unique approach in epidemiological research. We present here 2
      player and multiplayer noncooperative games where players are defined by HIV
      status and age and may engage in casual (sexual) encounters. The games are
      modelled as generalized Nash games with shared constraints, which is completely
      novel in the context of our applied problem. Each player's HIV status is known to
      potential partners, and players have personal preferences ranked via utility
      values of unprotected and protected sex outcomes. We model a player's strategy as
      their probability of being engaged in a casual unprotected sex encounter (USE),
      which may lead to HIV transmission; however, we do not incorporate a transmission
      model here. We study the sensitivity of Nash strategies with respect to varying
      preference rankings, and the impact of a prophylactic vaccine introduced in
      players of youngest age groups. We also study the effect of these changes on the
      overall increase in infection level, as well as the effects that a potential
      prophylactic treatment may have on age-stratified groups of players. We conclude
      that the biggest impacts on increasing the infection levels in the overall
      population are given by the variation in the utilities assigned to individuals
      for unprotected sex with others of opposite HIV status, while the introduction of
      a prophylactic vaccine in youngest age group (15-20 yr olds) slows down the
      increase in HIV infection.

PMID- 27879105
TI  - Optimal control analysis of malaria-schistosomiasis co-infection dynamics.
AB  - This paper presents a mathematical model for malaria--schistosomiasis co
      infection in order to investigate their synergistic relationship in the presence
      of treatment. We first analyse the single infection steady states, then
      investigate the existence and stability of equilibria and then calculate the
      basic reproduction numbers. Both the single-infection models and the co-infection
      model exhibit backward bifurcations. We carrying out a sensitivity analysis of
      the co-infection model and show that schistosomiasis infection may not be
      associated with an increased risk of malaria. Conversely, malaria infection may
      be associated with an increased risk of schistosomiasis. Furthermore, we found
      that effective treatment and prevention of schistosomiasis infection would also
      assist in the effective control and eradication of malaria. Finally, we apply
      Pontryagin's Maximum Principle to the model in order to determine optimal
      strategies for control of both diseases.

PMID- 27879106
TI  - Global existence and uniqueness of classical solutions for a generalized
      quasilinear parabolic equation with application to a glioblastoma growth model.
AB  - This paper studies the global existence and uniqueness of classical solutions for
      a generalized quasilinear parabolic equation with appropriate initial and mixed
      boundary conditions. Under some practicable regularity criteria on diffusion item
      and nonlinearity, we establish the local existence and uniqueness of classical
      solutions based on a contraction mapping. This local solution can be continued
      for all positive time by employing the methods of energy estimates, Lp-theory,
      and Schauder estimate of linear parabolic equations. A straightforward
      application of global existence result of classical solutions to a density
      dependent diffusion model of in vitro glioblastoma growth is also presented.

PMID- 27879107
TI  - Global stability of a multistrain SIS model with superinfection.
AB  - In this paper, we study the global stability of a multistrain SIS model with
      superinfection. We present an iterative procedure to calculate a sequence of
      reproduction numbers, and we prove that it completely determines the global
      dynamics of the system. We show that for any number of strains with different
      infectivities, the stable coexistence of any subset of the strains is possible,
      and we completely characterize all scenarios. As an example, we apply our method
      to a three-strain model.

PMID- 27879108
TI  - Detecting phase transitions in collective behavior using manifold's curvature.
AB  - If a given behavior of a multi-agent system restricts the phase variable to an
      invariant manifold, then we define a phase transition as a change of physical
      characteristics such as speed, coordination, and structure. We define such a
      phase transition as splitting an underlying manifold into two sub-manifolds with
      distinct dimensionalities around the singularity where the phase transition
      physically exists. Here, we propose a method of detecting phase transitions and
      splitting the manifold into phase transitions free sub-manifolds. Therein, we
      firstly utilize a relationship between curvature and singular value ratio of
      points sampled in a curve, and then extend the assertion into higher-dimensions
      using the shape operator. Secondly, we attest that the same phase transition can
      also be approximated by singular value ratios computed locally over the data in a
      neighborhood on the manifold. We validate the Phase Transition Detection (PTD)
      method using one particle simulation and three real world examples.

PMID- 27879110
TI  - Population models with quasi-constant-yield harvest rates.
AB  - One-dimensional logistic population models with quasi-constant-yield harvest
      rates are studied under the assumptions that a population inhabits a patch of
      dimensionless width and no members of the population can survive outside of the
      patch. The essential problem is to determine the size of the patch and the ranges
      of the harvesting rate functions under which the population survives or becomes
      extinct. This is the first paper which discusses such models with the Dirichlet
      boundary conditions and can tell the exact quantity of harvest rates of the
      species without having the population die out. The methodology is to establish
      new results on the existence of positive solutions of semi-positone Hammerstein
      integral equations using the fixed point index theory for compact maps defined on
      cones, and apply the new results to tackle the essential problem. It is expected
      that the established analytical results have broad applications in management of
      sustainable ecological systems.

PMID- 27879109
TI  - Altruistic aging: The evolutionary dynamics balancing longevity and evolvability.
AB  - Altruism is typically associated with traits or behaviors that benefit the
      population as a whole, but are costly to the individual. We propose that, when
      the environment is rapidly changing, senescence (age-related deterioration) can
      be altruistic. According to numerical simulations of an agent-based model, while
      long-lived individuals can outcompete their short lived peers, populations
      composed of long-lived individuals are more likely to go extinct during periods
      of rapid environmental change. Moreover, as in many situations where other
      cooperative behavior arises, senescence can be stabilized in a structured
      population.

PMID- 27879111
TI  - Modelling chemistry and biology after implantation of a drug-eluting stent. Part
      I: Drug transport.
AB  - Drug-eluting stents have been used widely to prevent restenosis of arteries
      following percutaneous balloon angioplasty. Mathematical modelling plays an
      important role in optimising the design of these stents to maximise their
      efficiency. When designing a drug-eluting stent system, we expect to have a
      sufficient amount of drug being released into the artery wall for a sufficient
      period to prevent restenosis. In this paper, a simple model is considered to
      provide an elementary description of drug release into artery tissue from an
      implanted stent. From the model, we identified a parameter regime to optimise the
      system when preparing the polymer coating. The model provides some useful order
      of magnitude estimates for the key quantities of interest. From the model, we can
      identify the time scales over which the drug traverses the artery wall and
      empties from the polymer coating, as well as obtain approximate formulae for the
      total amount of drug in the artery tissue and the fraction of drug that has
      released from the polymer. The model was evaluated by comparing to in-vivo
      experimental data and good agreement was found.

PMID- 27879112
TI  - Machine learning of swimming data via wisdom of crowd and regression analysis.
AB  - Every performance, in an officially sanctioned meet, by a registered USA swimmer
      is recorded into an online database with times dating back to 1980. For the first
      time, statistical analysis and machine learning methods are systematically
      applied to 4,022,631 swim records. In this study, we investigate performance
      features for all strokes as a function of age and gender. The variances in
      performance of males and females for different ages and strokes were studied, and
      the correlations of performances for different ages were estimated using the
      Pearson correlation. Regression analysis show the performance trends for both
      males and females at different ages and suggest critical ages for peak training.
      Moreover, we assess twelve popular machine learning methods to predict or
      classify swimmer performance. Each method exhibited different strengths or
      weaknesses in different cases, indicating no one method could predict well for
      all strokes. To address this problem, we propose a new method by combining
      multiple inference methods to derive Wisdom of Crowd Classifier (WoCC). Our
      simulation experiments demonstrate that the WoCC is a consistent method with
      better overall prediction accuracy. Our study reveals several new age-dependent
      trends in swimming and provides an accurate method for classifying and predicting
      swimming times.

PMID- 27879113
TI  - Dynamical analysis of a toxin-producing phytoplankton-zooplankton model with
      refuge.
AB  - To study the impacts of toxin produced by phytoplankton and refuges provided for
      phytoplankton on phytoplankton-zooplankton interactions in lakes, we establish a
      simple phytoplankton-zooplankton system with Holling type II response function.
      The existence and stability of positive equilibria are discussed. Bifurcation
      analyses are given by using normal form theory which reveals reasonably the
      mechanisms and nonlinear dynamics of the effects of toxin and refuges, including
      Hopf bifurcation, Bogdanov-Takens bifurcation of co-dimension 2 and 3. Numerical
      simulations are carried out to intuitively support our analytical results and
      help to explain the observed biological behaviors. Our findings finally show that
      both phytoplankton refuge and toxin have a significant impact on the occurring
      and terminating of algal blooms in freshwater lakes.

PMID- 27879114
TI  - Global stability and uniform persistence of the reaction-convection-diffusion
      cholera epidemic model.
AB  - We study the global stability issue of the reaction-convection-diffusion cholera
      epidemic PDE model and show that the basic reproduction number serves as a
      threshold parameter that predicts whether cholera will persist or become globally
      extinct. Specifically, when the basic reproduction number is beneath one, we show
      that the disease-free-equilibrium is globally attractive. On the other hand, when
      the basic reproduction number exceeds one, if the infectious hosts or the
      concentration of bacteria in the contaminated water are not initially identically
      zero, we prove the uniform persistence result and that there exists at least one
      positive steady state.

PMID- 27879116
TI  - Angiogenesis model with Erlang distributed delays.
AB  - We consider the model of angiogenesis process proposed by Bodnar and Forys (2009)
      with time delays included into the vessels formation and tumour growth processes.
      Originally, discrete delays were considered, while in the present paper we focus
      on distributed delays and discuss specific results for the Erlang distributions.
      Analytical results concerning stability of positive steady states are illustrated
      by numerical results in which we also compare these results with those for
      discrete delays.

PMID- 27879115
TI  - Preface.
AB  - This volume was inspired by the topics presented at the international conference
      "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in
      Bedlewo, Poland. System biology is an approach which tries to understand how
      micro systems, at the molecular and cellular levels, affect macro systems such as
      organs, tissue and populations. Thus it is not surprising that a major theme of
      this volume evolves around cancer and its treatment. Articles on this topic
      include models for tumor induced angiogenesis, without and with delays,
      metastatic niche of the bone marrow, drug resistance and metronomic chemotherapy,
      and virotherapy of glioma. Methods range from dynamical systems to optimal
      control. Another well represented topic of this volume is mathematical modeling
      in epidemiology. Mathematical approaches to modeling and control of more specific
      diseases like malaria, Ebola or human papillomavirus are discussed as well as a
      more general approaches to the SEIR, and even more general class of models in
      epidemiology, by using the tools of optimal control and optimization. The volume
      also brings up challenges in mathematical modeling of other diseases such as
      tuberculosis. Partial differential equations combined with numerical approaches
      are becoming important tools in modeling not only tumor growth and treatment, but
      also other diseases, such as fibrosis of the liver, and atherosclerosis and its
      associated blood flow dynamics, and our volume presents a state of the art
      approach on these topics. Understanding mathematics behind the cell motion,
      appearance of the special patterns in various cell populations, and age
      structured mutations are among topics addressed inour volume. A spatio-temporal
      models of synthetic genetic oscillators brings the analysis to the gene level
      which is the focus of much of current biological research. Mathematics can help
      biologists to explain the collective behavior of bacterial, a topic that is also
      presented here. Finally some more across the discipline topics are being
      addresses, which can appear as a challenge in studying problems in systems
      biology on all, macro, meso and micro levels. They include numerical approaches
      to stochastic wave equation arising in modeling Brownian motion, discrete
      velocity models, many particle approximations as well as very important aspect on
      the connection between discrete measurement and the construction of the models
      for various phenomena, particularly the one involving delays. With the variety of
      biological topics and their mathematical approaches we very much hope that the
      reader of the Mathematical Biosciences and Engineering will find this volume
      interesting and inspirational for their own research.

PMID- 27879117
TI  - A singular limit for an age structured mutation problem.
AB  - The spread of a particular trait in a cell population often is modelled by an
      appropriate system of ordinary differential equations describing how the sizes of
      subpopulations of the cells with the same genome change in time. On the other
      hand, it is recognized that cells have their own vital dynamics and mutations,
      leading to changes in their genome, mostly occurring during the cell division at
      the end of its life cycle. In this context, the process is described by a system
      of McKendrick type equations which resembles a network transport problem. In this
      paper we show that, under an appropriate scaling of the latter, these two
      descriptions are asymptotically equivalent.

PMID- 27879118
TI  - On the initial value problem for a class of discrete velocity models.
AB  - In this paper we investigate the initial value problem for a class of hyperbolic
      systems relating the mathematical modeling of a class of complex phenomena, with
      emphasis on vehicular traffic flow. Existence and uniqueness for large times of
      solutions, a basic requisite both for models building and for their numerical
      implementation, are obtained under weak hypotheses on the terms modeling the
      interaction among agents. The results are then compared with the existing
      literature on the subject.

PMID- 27879119
TI  - On the mathematical modelling of tumor-induced angiogenesis.
AB  - An angiogenic system is taken as an example of extremely complex ones in the
      field of Life Sciences, from both analytical and computational points of view,
      due to the strong coupling between the kinetic parameters of the relevant
      branching - growth - anastomosis stochastic processes of the capillary network,
      at the microscale, and the family of interacting underlying biochemical fields,
      at the macroscale. To reduce this complexity, for a conceptual stochastic model
      we have explored how to take advantage of the system intrinsic multiscale
      structure: one might describe the stochastic dynamics of the cells at the vessel
      tip at their natural microscale, whereas the dynamics of the underlying fields is
      given by a deterministic mean field approximation obtained by an averaging at a
      suitable mesoscale. But the outcomes of relevant numerical simulations show that
      the proposed model, in presence of anastomosis, is not self-averaging, so that
      the ''propagation of chaos" assumption cannot be applied to obtain a
      deterministic mean field approximation. On the other hand we have shown that
      ensemble averages over many realizations of the stochastic system may better
      correspond to a deterministic reaction-diffusion system.

PMID- 27879120
TI  - Network-based analysis of a small Ebola outbreak.
AB  - We present a method for estimating epidemic parameters in network-based
      stochastic epidemic models when the total number of infections is assumed to be
      small. We illustrate the method by reanalyzing the data from the 2014 Democratic
      Republic of the Congo (DRC) Ebola outbreak described in Maganga et al. (2014).

PMID- 27879121
TI  - Emergence of spatial patterns in a mathematical model for the co-culture dynamics
      of epithelial-like and mesenchymal-like cells.
AB  - Accumulating evidence indicates that the interaction between epithelial and
      mesenchymal cells plays a pivotal role in cancer development and metastasis
      formation. Here we propose an integro-differential model for the co-culture
      dynamics of epithelial-like and mesenchymal-like cells. Our model takes into
      account the effects of chemotaxis, adhesive interactions between epithelial-like
      cells, proliferation and competition for nutrients. We present a sample of
      numerical results which display the emergence of spots, stripes and honeycomb
      patterns, depending on parameters and initial data. These simulations also
      suggest that epithelial-like and mesenchymal-like cells can segregate when there
      is little competition for nutrients. Furthermore, our computational results
      provide a possible explanation for how the concerted action between epithelial
      cell adhesion and mesenchymal-cell spreading can precipitate the formation of
      ring-like structures, which resemble the fibrous capsules frequently observed in
      hepatic tumours.

PMID- 27879122
TI  - Controlling imported malaria cases in the United States of America.
AB  - We extend the mathematical malaria epidemic model framework of Dembele et al. and
      use it to ''capture" the 2013 Centers for Disease Control and Prevention (CDC)
      reported data on the 2011 number of imported malaria cases in the USA.
      Furthermore, we use our ''fitted" malaria models for the top 20 countries of
      malaria acquisition by USA residents to study the impact of protecting USA
      residents from malaria infection when they travel to malaria endemic areas, the
      impact of protecting residents of malaria endemic regions from mosquito bites and
      the impact of killing mosquitoes in those endemic areas on the CDC number of
      imported malaria cases in USA. To significantly reduce the number of imported
      malaria cases in USA, for each top 20 country of malaria acquisition by USA
      travelers, we compute the optimal proportion of USA international travelers that
      must be protected against malaria infection and the optimal proportion of
      mosquitoes that must be killed.

PMID- 27879123
TI  - On application of optimal control to SEIR normalized models: Pros and cons.
AB  - In this work we normalize a SEIR model that incorporates exponential natural
      birth and death, as well as disease-caused death. We use optimal control to
      control by vaccination the spread of a generic infectious disease described by a
      normalized model with L1 cost. We discuss the pros and cons of SEIR normalized
      models when compared with classical models when optimal control with L1 costs are
      considered. Our discussion highlights the role of the cost. Additionally, we
      partially validate our numerical solutions for our optimal control problem with
      normalized models using the Maximum Principle.

PMID- 27879124
TI  - Many particle approximation of the Aw-Rascle-Zhang second order model for
      vehicular traffic.
AB  - We consider the follow-the-leader approximation of the Aw-Rascle-Zhang (ARZ)
      model for traffic flow in a multi population formulation. We prove rigorous
      convergence to weak solutions of the ARZ system in the many particle limit in
      presence of vacuum. The result is based on uniform BV estimates on the discrete
      particle velocity. We complement our result with numerical simulations of the
      particle method compared with some exact solutions to the Riemann problem of the
      ARZ system.

PMID- 27879125
TI  - Mathematical modeling of liver fibrosis.
AB  - Fibrosis is the formation of excessive fibrous connective tissue in an organ or
      tissue, which occurs in reparative process or in response to inflammation.
      Fibrotic diseases are characterized by abnormal excessive deposition of fibrous
      proteins, such as collagen, and the disease is most commonly progressive, leading
      to organ disfunction and failure. Although fibrotic diseases evolve in a similar
      way in all organs, differences may occur as a result of structure and function of
      the specific organ. In liver fibrosis, the gold standard for diagnosis and
      monitoring the progression of the disease is biopsy, which is invasive and cannot
      be repeated frequently. For this reason there is currently a great interest in
      identifying non-invasive biomarkers for liver fibrosis. In this paper, we develop
      for the first time a mathematical model of liver fibrosis by a system of partial
      differential equations. We use the model to explore the efficacy of potential and
      currently used drugs aimed at blocking the progression of liver fibrosis. We also
      use the model to develop a diagnostic tool based on a combination of two
      biomarkers.

PMID- 27879126
TI  - Estimation of initial functions for systems with delays from discrete
      measurements.
AB  - The work presents a gradient-based approach to estimation of initial functions of
      time delay elements appearing in models of dynamical systems. It is shown how to
      generate the gradient of the estimation objective function in the initial
      function space using adjoint sensitivity analysis. It is assumed that the system
      is continuous-time and described by ordinary differential equations with delays
      but the estimation is done based on discrete-time measurements of the signals
      appearing in the system. Results of gradient-based estimation of initial
      functions for exemplary models are presented and discussed.

PMID- 27879127
TI  - Numerical simulations of a 3D fluid-structure interaction model for blood flow in
      an atherosclerotic artery.
AB  - The inflammatory process of atherosclerosis leads to the formation of an
      atheromatous plaque in the intima of the blood vessel. The plaque rupture may
      result from the interaction between the blood and the plaque. In each cardiac
      cycle, blood interacts with the vessel, considered as a compliant nonlinear
      hyperelastic. A three dimensional idealized fluid-structure interaction (FSI)
      model is constructed to perform the blood-plaque and blood-vessel wall
      interaction studies. An absorbing boundary condition (BC) is imposed directly on
      the outflow in order to cope with the spurious reflexions due to the truncation
      of the computational domain. The difference between the Newtonian and non
      Newtonian effects is highlighted. It is shown that the von Mises and wall shear
      stresses are significantly affected according to the rigidity of the wall. The
      numerical results have shown that the risk of plaque rupture is higher in the
      case of a moving wall, while in the case of a fixed wall the risk of progression
      of the atheromatous plaque is higher.

PMID- 27879128
TI  - Local controllability and optimal control for a model of combined anticancer
      therapy with control delays.
AB  - We study some control properties of a class of two-compartmental models of
      response to anticancer treatment which combines anti-angiogenic and cytotoxic
      drugs and take into account multiple control delays. We formulate sufficient
      local controllability conditions for semilinear systems resulting from these
      models. The control delays are related to PK/PD effects and some clinical
      recommendations, e.g., normalization of the vascular network. The optimized
      protocols of the combined therapy for the model, considered as solutions to an
      optimal control problem with delays in control, are found using necessary
      conditions of optimality and numerical computations. Our numerical approach uses
      dicretization and nonlinear programming methods as well as the direct
      optimization of switching times. The structural sensitivity of the considered
      control properties and optimal solutions is also discussed.

PMID- 27879129
TI  - On drug resistance and metronomic chemotherapy: A mathematical modeling and
      optimal control approach.
AB  - Effects that tumor heterogeneity and drug resistance have on the structure of
      chemotherapy protocols are discussed from a mathematical modeling and optimal
      control point of view. In the case when two compartments consisting of sensitive
      and resistant cells are considered, optimal protocols consist of full dose
      chemotherapy as long as the relative proportion of sensitive cells is high. When
      resistant cells become more dominant, optimal controls switch to lower dose
      regimens defined by so-called singular controls. The role that singular controls
      play in the structure of optimal therapy protocols for cell populations with a
      large number of traits is explored in mathematical models.

PMID- 27879130
TI  - Newton's method for nonlinear stochastic wave equations driven by one-dimensional
      Brownian motion.
AB  - We consider nonlinear stochastic wave equations driven by one-dimensional white
      noise with respect to time. The existence of solutions is proved by means of
      Picard iterations. Next we apply Newton's method. Moreover, a second-order
      convergence in a probabilistic sense is demonstrated.

PMID- 27879131
TI  - Spatio-temporal models of synthetic genetic oscillators.
AB  - Signal transduction pathways play a major role in many important aspects of
      cellular function e.g. cell division, apoptosis. One important class of signal
      transduction pathways is gene regulatory networks (GRNs). In many GRNs, proteins
      bind to gene sites in the nucleus thereby altering the transcription rate. Such
      proteins are known as transcription factors. If the binding reduces the
      transcription rate there is a negative feedback leading to oscillatory behaviour
      in mRNA and protein levels, both spatially (e.g. by observing fluorescently
      labelled molecules in single cells) and temporally (e.g. by observing
      protein/mRNA levels over time). Recent computational modelling has demonstrated
      that spatial movement of the molecules is a vital component of GRNs and may cause
      the oscillations. These numerical findings have subsequently been proved
      rigorously i.e. the diffusion coefficient of the protein/mRNA acts as a
      bifurcation parameter and gives rise to a Hopf bifurcation. In this paper we
      first present a model of the canonical GRN (the Hes1 protein) and show the effect
      of varying the spatial location of gene and protein production sites on the
      oscillations. We then extend the approach to examine spatio-temporal models of
      synthetic gene regulatory networks e.g. n-gene repressilators and activator
      repressor systems.

PMID- 27879132
TI  - Sufficient optimality conditions for a class of epidemic problems with control on
      the boundary.
AB  - In earlier paper of V. Capasso et al it is considered a simply model of
      controlling an epidemic, which is described by three functionals and systems of
      two PDE equations having the feedback operator on the boundary. Necessary
      optimality conditions and two gradient-type algorithms are derived. This paper
      constructs dual dynamic programming method to derive sufficient optimality
      conditions for optimal solution as well epsilon-optimality conditions in terms of
      dual dynamic inequalities. Approximate optimality and numerical calculations are
      presented too.

PMID- 27879133
TI  - A criterion of collective behavior of bacteria.
AB  - It was established in the previous works that hydrodynamic interactions between
      the swimmers can lead to collective motion. Its implicit evidences were confirmed
      by reduction in the effective viscosity. We propose a new quantitative criterion
      to detect such a collective behavior. Our criterion is based on a new
      computationally effective RVE (representative volume element) theory based on the
      basic statistic moments (e-sums or generalized Eisenstein-Rayleigh sums). The
      criterion can be applied to various two-phase dispersed media (biological
      systems, composites etc). The locations of bacteria are modeled by short segments
      having a small width randomly embedded in medium without overlapping. We compute
      the e-sums of the simulated disordered sets and of the observed experimental
      locations of Bacillus subtilis. The obtained results show a difference between
      these two sets that demonstrates the collective motion of bacteria.

PMID- 27879134
TI  - On a mathematical model of bone marrow metastatic niche.
AB  - We propose a mathematical model to describe tumor cells movement towards a
      metastasis location into the bone marrow considering the influence of chemotaxis
      inhibition due to the action of a drug. The model considers the evolution of the
      signaling molecules CXCL-12 secreted by osteoblasts (bone cells responsible of
      the mineralization of the bone) and PTHrP (secreted by tumor cells) which
      activates osteoblast growth. The model consists of a coupled system of second
      order PDEs describing the evolution of CXCL-12 and PTHrP, an ODE of logistic type
      to model the Osteoblasts density and an extra equation for each cancer cell. We
      also simulate the system to illustrate the qualitative behavior of the solutions.
      The numerical method of resolution is also presented in detail.

PMID- 27879135
TI  - The role of TNF-alpha inhibitor in glioma virotherapy: A mathematical model.
AB  - Virotherapy, using herpes simplex virus, represents a promising therapy of
      glioma. But the innate immune response, which includes TNF-alpha produced by
      macrophages, reduces the effectiveness of the treatment. Hence treatment with TNF
      alpha inhibitor may increase the effectiveness of the virotherapy. In the present
      paper we develop a mathematical model that includes continuous infusion of the
      virus in combination with TNF-alpha inhibitor. We study the efficacy of the
      treatment under different combinations of the two drugs for different scenarios
      of the burst size of newly formed virus emerging from dying infected cancer
      cells. The model may serve as a first step toward developing an optimal strategy
      for the treatment of glioma by the combination of TNF-alpha inhibitor and
      oncolytic virus injection.

PMID- 27879136
TI  - Optimal control of a tuberculosis model with state and control delays.
AB  - We introduce delays in a tuberculosis (TB) model, representing the time delay on
      the diagnosis and commencement of treatment of individuals with active TB
      infection. The stability of the disease free and endemic equilibriums is
      investigated for any time delay. Corresponding optimal control problems, with
      time delays in both state and control variables, are formulated and studied.
      Although it is well-known that there is a delay between two to eight weeks
      between TB infection and reaction of body's immune system to tuberculin, delays
      for the active infected to be detected and treated, and delays on the treatment
      of persistent latent individuals due to clinical and patient reasons, which
      clearly justifies the introduction of time delays on state and control measures,
      our work seems to be the first to consider such time-delays for TB and apply time
      delay optimal control to carry out the optimality analysis.

PMID- 27879137
TI  - A male-female mathematical model of human papillomavirus (HPV) in African
      American population.
AB  - We introduce mathematical human papillomavirus (HPV) epidemic models (with and
      without vaccination) for African American females (AAF) and African American
      males (AAM) with ''fitted'' logistic demographics and use these models to study
      the HPV disease dynamics. The US Census Bureau data of AAF and AAM of 16 years
      and older from 2000 to 2014 is used to ''fit'' the logistic demographic models.
      We compute the basic reproduction number, R0, and use it to show that R0 is less
      than 1 in the African American (AA) population with or without implementation of
      HPV vaccination program. Furthermore, we obtain that adopting a HPV vaccination
      policy in the AAF and AAM populations lower R0 and the number of HPV infections.
      Sensitivity analysis is used to illustrate the impact of each model parameter on
      the basic reproduction number.

PMID- 27879138
TI  - [Total pancreatectomy for pancreatic malignancy - from history to the present
      day].
AB  - Currently, total pancreatectomy (TP) is indicated in approximately one in ten
      surgical patients with pancreatic cancer. Key role in the decision falls in the
      competence of the multidisciplinary team, alternatively of the surgeon in the
      intraoperative period in some cases. Exceptionally, TP is approached in the so
      called salvage surgery. Perioperative mortality of TP as an elective procedure
      does not exceed that of partial resections; however, mortality of up to 50% is
      associated with salvage surgery in acute postoperative pancreatitis.
      Postoperatively, patients are afflicted with the so-called brittle diabetes
      comparable with type 1 diabetes. The aim of our overview is to inform about the
      current position of TP in the treatment of malignant pancreatic diseases.Key
      words: pancreatic cancer - total pancreatectomy - multidisciplinary team.

PMID- 27879139
TI  - [Liver metastases of malignant melanoma - utility of resection or radiofrequency
      ablation].
AB  - INTRODUCTION: Incidence of cutaneous and uveal forms of malignant melanoma (MM)
      has increased significantly in the population in the last years. Biological
      behavior of both these forms of MM is different and is associated with the
      development of liver metastases. The prognosis of patients with MM liver
      metastases is generally poor. The authors seek to consider the sense and the
      possibilities of surgical treatment of MM liver metastases. METHOD: Seven
      patients with liver metastases of MM were operated on in the Hepatobiliary Center
      of the Department of Surgery, University Hospital in Pilsen during the last ten
      years. Four patients suffered from the uveal and three from the cutaneous form of
      MM. Mean age of the patients was 58.8 years. R0 liver resection was performed in
      3, and radiofrequency ablation in 1 patient. In the remaining 3 patients the
      operation finished by exploratory laparotomy due to tumor progression. RESULTS:
      Two patients died in the interval of 6 and 25 months after liver surgery for
      tumor dissemination. Two patients continue to show disease free survival,
      currently of 22 and 28 months. CONCLUSION: Liver metastases of MM have a very
      poor prognosis. Surgical treatment indicated by the multidisciplinary team
      provides, together with further multimodal treatment, a chance for long-term
      survival and its indication is justified in selected patients.Key words:
      malignant melanoma - liver metastases - surgical treatment.

PMID- 27879140
TI  - [Fluorescence angiography in the detection of anastomotic perfusion during rectal
      and sigmoid resection - preliminary report].
AB  - INTRODUCTION: The aim of the study was to evaluate the results of fluorescence
      angiography for assessing anastomotic perfusion after resection of the sigmoid
      colon and rectum since its introduction into clinical practice at the authors'
      workplace and to evaluate the incidence of necessary resection line repositioning
      based on the quality of perfusion, and also to record any complications in
      anastomotic healing. METHOD: Retrospective unicentric analysis of prospectively
      collected data from patients with resection of the sigmoid colon and rectum with
      primary anastomosis. The patient set included 50 patients, 27 males and 23
      females; the median age was 64.5 years (33-80). Forty-four patients were
      indicated for resection for cancer of the sigmoid colon or rectum, while 6
      patients had a benign disease. Twenty-nine patients underwent total mesorectal
      excision with coloanal mechanical or hand-sewn anastomosis and 21 underwent
      resection of the sigmoid colon or upper rectum with mechanical anastomosis. Prior
      to the construction of the anastomosis, assessment of perfusion of the
      anastomotic segments by near infrared (NIR) indocyanine green (ICG) fluorescence
      angiography was performed in all patients. The quality of perfusion of the
      mesocolon and bowel wall and its impact on moving the resection line and
      complications of anastomotic healing 30 days postoperatively were all evaluated.
      RESULTS: Assessment of perfusion using fluorescence angiography was technically
      successfully performed in all 50 patients. In 5 cases (10%) the resection line
      had to be moved for signs of poor perfusion of the bowel wall. Postoperatively,
      healing of the anastomosis was complicated in four patients (8%). Dehiscence was
      recorded in 3 patients (10.3%) with total mesorectal excision and in 1 patient
      (4.8%) after resection of the sigmoid colon and upper rectum. CONCLUSION: The
      presented results indicate that fluorescence angiography may lead to a decrease
      in the incidence of anastomotic dehiscence after colorectal resections by mapping
      in detail the perfusion of the anastomosed segments.Key words: fluorescence
      angiography - indocyanine green - anastomotic leak - colorectal resection.

PMID- 27879142
TI  - [Myxofibrosarcoma in the abdominal cavity].
AB  - A number of benign and malignant tumors may develop in the abdominal cavity.
      Sarcomas are rather rare tumors of the abdominal cavity. They are often diagnosed
      at advanced growth stages as their local growth can cause clinical problems to
      the patients. The author presents a case report of myxofibrosarcoma in the
      abdominal cavity.Key words: myxofibrosarcoma.

PMID- 27879141
TI  - [Complete mesocolic excision during right hemicolectomy].
AB  - INTRODUCTION: Complete mesocolic excision (CME) ensures the removal of all
      sentinel and regional lymph nodes during colon cancer surgery. For right-sided
      hemicolectomy it is essential to dissect the wall of vena mesenterica superior,
      which increases the risk of injuring surrounding organs. So far, no randomized
      studies comparing long-term oncological results of standard right hemicolectomy
      and hemicolectomy with CME have been published. METHOD: 83 patients operated for
      colon carcinoma in 2014 and 2015 were included in this study, all of them
      undergoing right-sided hemicolectomy using laparotomy access. The standard
      procedure was done in 63 cases and hemicolectomy with CME was done in 20 cases.
      We compared the incidence of complications, and the characteristics and
      descriptions of obtained specimens evaluated by a pathologist for both groups.
      RESULTS: The operation times of right-sided hemicolectomies with CME was longer
      by 20 minutes on average. The incidence of postoperative complications was
      similar in both groups. Pancreatic fistula in the group of patients undergoing
      right-sided hemicolectomy with CME was an unusual complication; the fistula was
      healed through conservative treatment. Comparing the resecate parameters, we
      found no significant differences in the lengths of the resected terminal ileum.
      But the length of the resected colon was significantly longer for the CME
      technique (median 42 cm versus 22 cm). The incidence of lymph node metastases was
      similar in both groups. However, the total number of removed lymph nodes in the
      group with CME was significantly higher (median 23). CONCLUSION: Right-sided
      hemicolectomy with complete mesocolic excision offers the removal of more lymph
      nodes than the standard technique. The central vascular ligation technique
      elongates the operation time and may be associated with more intraoperative
      injuries. Introduction of the concept of complete mesocolic excision is derived
      from an effort to standardize the surgical technique for colon cancer
      resection.Key words: right-sided hemicolectomy complete mesocolic excision colon
      cancer lymphadenectomy.

PMID- 27879143
TI  - [Perforated jejunal diverticulitis].
AB  - Jejunal diverticulosis is a rare disorder and the course of the disease is mostly
      asymptomatic. Surgical treatment is generally needed in case of complications in
      the acute phase of the disease, when the disease symptoms most commonly include
      bleeding and perforation. Jejunum is difficult to examine using the common
      visualization methods and endoscopic methods. The authors present case reports of
      a 92 years old female patient and a 66 years old male patient operated for
      perforated jejunal diverticles.Key words: acute abdomen jejunal diverticulitis
      perforation.

PMID- 27879144
TI  - [Recurrent retroperitoneal sarcoma].
AB  - Retroperitoneal sarcomas are rare malignant neoplasms that are often diagnosed
      late because of their typical nonspecific symptomatology. Radical surgical
      resection, if possible given the local anatomical conditions, is the most
      important treatment modality. However, even if the surgery is feasible and
      successful, the prognosis of retroperitoneal sarcoma is not good. The most
      frequent type of recurrence is local recurrence, and radical surgical resection
      remains the most important treatment modality even in such cases.Our study
      presents a case report of a patient with a retroperitoneal leiomyosarcoma that
      was radically (R0) removed. Two years later a local recurrence developed, which
      was eventually diagnosed by MRI. Again, radical (R0) surgical resection was
      approached (because of tumor invasion into inferior caval vein, the vein had to
      be partially resected as well and substituted with a vascular prosthesis).The
      report describes a relatively typical case of retroperitoneal sarcoma, while
      pointing out the importance of timely diagnosis (which is definitely not easy to
      achieve) and especially of radical surgical treatment.Key words: retroperitoneal
      sarcoma recurrence surgery.

PMID- 27879145
TI  - Variations in endothelin receptor B subtype 2 (EDNRB2) coding sequences and mRNA
      expression levels in 4 Muscovy duck plumage colour phenotypes.
AB  - 1. Endothelin receptor B subtype 2 (EDNRB2) is a paralog of EDNRB, which encodes
      a 7-transmembrane G-protein coupled receptor. Previous studies reported that
      EDNRB was essential for melanoblast migration in mammals and ducks. 2. Muscovy
      ducks have different plumage colour phenotypes. Variations in EDNRB2 coding
      sequences (CDSs) and mRNA expression levels were investigated in 4 different
      Muscovy duck plumage colour phenotypes, including black, black mutant, silver and
      white head. 3. The EDNRB2 gene from Muscovy duck was cloned; it had a length of
      6435 bp and encoded 437 amino acids. The coding region was screened and potential
      single nucleotide polymorphisms were identified. Eight mutations were obtained,
      including one missense variant (c.64C > T) and 7 synonymous substitutions. The
      substitutions were associated with plumage colour phenotypes. 4. The EDNRB2 mRNA
      expression levels were compared between feather pulp from black birds and black
      mutant birds. The results indicated that EDNRB2 transcripts in feather pulp were
      significantly higher in black feathers than in white feathers. 5. The results
      determined the variation of EDNRB2 CDS and mRNA expression in Muscovy ducks of
      various plumage colours.

PMID- 27879146
TI  - Chemical composition and antifungal activity of essential oils from medicinal
      plants of Kazakhstan.
AB  - The composition of essential oils from leaves of Kazakhstan medicinal plants was
      analysed by GC-MS. The major compounds identified were 1,8-cineole (34.2%),
      myrcene (19.1%) and alpha-pinene (9.4%) in Ajania fruticulosa; 1,8-cineole
      (21.0%), beta-thujone (11.0%), camphor (8.5%), borneol (7.3%) and alpha-thujone
      (6.5%), in Achillea nobilis; camphor (47.3%), 1,8-cineole (23.9%), camphene
      (9.8%) and beta-thujone (6.0%) in Artemisia terrae-albae; 1,8-cineole(55.8%) and
      beta-pinene (6.2%) in Hyssopus ambiguus; alpha-thuyene(46.3%) and delta
      cadinene(6.3%) in Juniperus sibirica; sabinene (64%) in Juniperus sabina; and
      alpha-pinene (51.5%), beta-phellandrene (11.2%) and delta-cadinene (6.3%) in
      Pinus sibirica. The essential oils did not show antifungal effect (MIC > 1.20
      mg/mL) on Aspergillus carbonarius and Aspergillus niger, while the oils from A.
      nobilis, A. terrae-albae, H. ambiguus and J. sabina exhibited moderate and
      moderate to weak antimicrobial activities on Fusarium verticillioides (MIC = 0.60
      mg/mL) and Fusarium graminearum (MIC = 0.60-1.20 mg/mL), respectively. A
      principal component analysis associated the antifungal activity (r2 > 0.80, p =
      0.05) with the presence of borneol, camphor, camphene, 1,8-cineole,alpha- and
      beta-thujone, and of the oxygenated monoterpenes.

PMID- 27879148
TI  - Corrigendum.

PMID- 27879147
TI  - Pre-transplantation novel agent induction predicts progression-free survival for
      patients with immunoglobulin light-chain amyloidosis undergoing high-dose
      melphalan and autologous stem cell transplantation.
AB  - INTRODUCTION: High-dose melphalan and autologous stem cell transplantation
      (HDM/SCT) is an effective treatment modality for immunoglobulin light-chain (AL)
      amyloidosis; however, its application remains restricted to patients with good
      performance status and limited organ involvement. In recent years, the paradigm
      for AL amyloidosis has changed with the introduction of novel agents such as
      immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). We hypothesized
      that use of novel agent induction regimens has improved outcomes for patients
      with AL amyloidosis undergoing HDM/SCT at our center. METHODS: All patients with
      AL amyloidosis, age >=18 years who underwent HDM/SCT between 2001 and 2014 at the
      Fred Hutchinson Cancer Research Center and University of Washington Medical
      Center were included in this study. Any regimen administered within 6 months
      prior to HDM/SCT including an IMiD or a PI was considered a novel induction
      regimen. Use of induction regimen was evaluated in a Cox proportional hazard
      model for association with progression-free survival (PFS) and overall survival
      (OS). RESULTS: Forty-five patients with AL amyloidosis underwent HDM/SCT. The
      median age was 57.2 years (range 39-74.4), 15 (33.3%) were women. The median
      number of organs involved was 2 (range 1-5), with 20 patients having only 1
      (44.4%), 10 patients having 2 (22.2%), and 15 patients (33.3%) having >= 3 organs
      involved. Novel agent induction regimens were used prior to HDM/SCT in 21
      patients (46.7%); these comprised PI in 13/21 (57.1%), IMiD alone in 6/21
      (28.6%), PI and cyclophosphamide (CyBorD) in 3/21 (14.3%), and IMiD and PI in
      3/21 (14.3%). Use of a novel agent induction regimen was associated with
      improved, but not OS. The 3-year PFS for patients who received a novel agent
      induction was 79%, while for those who did not was 53% (hazard ratio [HR] =
      0.317, p = 0.048). The 3-year OS for patients who received novel agent induction
      regimens was 95%, while for those who did not was 71% (HR = 0.454, p = 0.247).
      DISCUSSION: Our data suggest that use of a novel agent induction regimen
      including an IMiD or PI prior to HDM/SCT for patients with AL amyloidosis could
      improve outcomes, with improvement in PFS. Although these results are limited by
      sample size and lack of randomization, these results support possible further
      investigation of novel agent induction regimens in the context of a prospective
      clinical trial.

PMID- 27879149
TI  - Increasing amount of amyloid are associated with the severity of clinical
      features in hereditary gelsolin (AGel) amyloidosis.
AB  - BACKGROUND: Patients with hereditary gelsolin (AGel) amyloidosis (HGA) present
      with hanging skin (cutis laxa) and bilateral cranial neuropathy, and require
      symptomatic plastic surgery. Our clinical observation of tissue fragility
      prompted us to design a prospective study. METHODS: Twenty-nine patients with HGA
      undergoing surgery were interviewed and clinically examined. The height and
      thickness of skin folds in standard anatomical localizations were measured. The
      presence and distribution of amyloid in skin samples were analyzed using Congo
      red staining and immunohistochemistry using antibodies against gelsolin amyloid
      (AGel) subunit. RESULTS: The measured skin folds stretched more in patients with
      HGA (e.g. skin over olecranon, p < 0.001). The skin folds were thinner in
      patients with HGA (e.g. forehead skin, p < 0.001). The skin and subcutaneous fat
      were abnormally fragile during surgery. The total amount of AGel amyloid, and its
      presence in the deep layers of the skin and subcutaneous fat correlated with the
      measurements of skin folds, age and extent of cranial neuropathy. CONCLUSIONS:
      The AGel amyloid in the skin and subcutis, together with morphologic changes in
      the dermal stroma and skin adnexa contribute to the atrophied and fragile
      structure of HGA skin. This is the first study to demonstrate the correlation
      between AGel amyloid accumulation and clinical disease severity.

PMID- 27879151
TI  - Overcoming drug resistance with on-demand charged thermoresponsive dendritic
      nanogels.
AB  - AIM: To develop nanogels (NG) able to modulate the encapsulation and release of
      drugs, in order to circumvent drug resistance mechanisms in cancer cells.
      MATERIALS & METHODS: Poly-N-isopropylacrylamide-dendritic polyglycerol NG were
      semi-interpenetrated with 2-acrylamido-2-methylpropane sulfonic acid or (2
      dimethylamino) ethyl methacrylate. Physico-chemical properties of the NGs as well
      as doxorubicin (DOXO) loading and release were characterized. Drug delivery
      performance was investigated in vitro and in vivo in a multidrug-resistant tumor
      model. RESULTS: Both the DOXO loaded semi-interpenetrating polymer network NGs
      were more efficient in multidrug resistant cancer cell proliferation inhibition
      studies. In vivo, the DOXO loaded NG semi-interpenetrated with 2-acrylamido-2
      methylpropane sulfonic acid was able to overcome drug resistance and reduce the
      tumor volume to about 25%. CONCLUSION: The innovative semi-interpenetrating
      polymer network NGs appear to be promising drug carriers for drug resistant
      cancer therapy.

PMID- 27879150
TI  - Acetabular cup position and risk of dislocation in primary total hip
      arthroplasty.
AB  - Background and purpose - Hip dislocation is one of the most common complications
      following total hip arthroplasty (THA). Several factors that affect dislocation
      have been identified, including acetabular cup positioning. Optimal values for
      cup inclination and anteversion are debatable. We performed a systematic review
      to describe the different methods for measuring cup placement, target zones for
      cup positioning, and the association between cup positioning and dislocation
      following primary THA. Methods - A systematic search of literature in the PubMed
      database was performed (January and February 2016) to identify articles that
      compared acetabular cup positioning and the risk of dislocation. Surgical
      approach and methods for measurement of cup angles were also considered. Results 
      28 articles were determined to be relevant to our research question. Some
      articles demonstrated that cup positioning influenced postoperative dislocation
      whereas others did not. The majority of articles could not identify a
      statistically significant difference between dislocating and non-dislocating THA
      with regard to mean angles of cup anteversion and inclination. Most of the
      articles that assessed cup placement within the Lewinnek safe zone did not show a
      statistically significant reduction in dislocation rate. Alternative target
      ranges have been proposed by several authors. Interpretation - The Lewinnek safe
      zone could not be justified. It is difficult to draw broad conclusions regarding
      a definitive target zone for cup positioning in THA, due to variability between
      studies and the likely multifactorial nature of THA dislocation. Future studies
      comparing cup positioning and dislocation rate should investigate surgical
      approach separately. Standardized tools for measurement of cup positioning should
      be implemented to allow comparison between studies.

PMID- 27879152
TI  - Preparation and immunogenicity of gold glyco-nanoparticles as antipneumococcal
      vaccine model.
AB  - AIM: Nanotechnology-based fully synthetic carbohydrate vaccines are promising
      alternatives to classic polysaccharide/protein conjugate vaccines. We have
      prepared gold glyco-nanoparticles (GNP) bearing two synthetic carbohydrate
      antigens related to serotypes 19F and 14 of Streptococcus pneumoniae and
      evaluated their immunogenicity in vivo. RESULTS: A tetrasaccharide fragment of
      serotype 14 (Tetra-14), a trisaccharide fragment of serotype 19F (Tri-19F), a T
      helper peptide and d -glucose were loaded onto GNP in different ratios. Mice
      immunization showed that the concomitant presence of Tri-19F and Tetra-14 on the
      same nanoparticle critically enhanced the titers of specific IgG antibodies
      toward type 14 polysaccharide compared with GNP exclusively displaying Tetra-14,
      while no IgG antibodies against type 19F polysaccharide were elicited.
      CONCLUSION: This work is a step forward toward synthetic nanosystems combining
      carbohydrate antigens and immunogenic peptides as potential carbohydrate-based
      vaccines.

PMID- 27879153
TI  - Polymeric micelles of suberoylanilide hydroxamic acid to enhance the anticancer
      potential in vitro and in vivo.
AB  - AIM: To improve the bioavailability and anticancer potential of suberoylanilide
      hydroxamic acid (SAHA) by developing a drug-loaded polymeric nanomicellar system.
      METHODS: SAHA-loaded Poly(ethylene glycol)-block-poly(caprolactone) (PEG-PCL)
      micelles were developed, and physico-chemically characterized. In vitro cellular
      uptake, viability and apoptosis-inducing ability of the SAHA-PEG-PCL micelles
      were investigated. In vivo anticancer activity was evaluated in C57BL/6 mice
      bearing tumor. RESULTS: The SAHA-PEG-PCL micelles had optimum size (~130 nm) with
      an entrapment efficiency of approximately 67%. The SAHA-PEG-PCL induced stronger
      cell cycle arrest in G2/M phase leading to higher rate of apoptosis compared to
      free SAHA. SAHA-PEG-PCL demonstrated significant tumor suppression compared to
      free SAHA in vivo. CONCLUSION: The physicochemical properties and the antitumor
      efficacy of SAHA were improved by encapsulating in polymeric micelles.

PMID- 27879154
TI  - 20 years since the International Society of the Ageing Male (ISSAM) was founded.

PMID- 27879157
TI  - Secondary submucosal vocal cyst following pulsed dye laser application for sulcus
      vocalis.
AB  - CONCLUSION: Submucosal vocal cyst can occur as a distinct long-term sequelae
      following pulsed dye laser (PDL) application for sulcus vocalis. It is
      recommended that the cyst lesion should be surgically removed for treatment.
      Optimal and precise irradiation of PDL is considered important to avoid the
      development of a such complication. OBJECTIVE: After several years of clinical
      practice and an extended period of follow-up of the patients who received PDL
      application in treating sulcus vocalis, the authors have encountered several
      cases of secondary submucosal vocal cyst development. Therefore, this study aims
      to investigate this late complication following PDL laryngeal surgery. METHODS:
      Patients who developed secondary submucosal vocal cyst after last PDL laryngeal
      surgery between March 2008 and January 2016 were analyzed after retrospectively
      reviewing clinical and operative data. RESULTS: There were a total 11 patients
      who had been identified as presenting secondary submucosal vocal cyst among 186
      patients who underwent PDL laryngeal surgery (5.9% incidence). All five patients
      who received surgery showed complete resolution and were free of symptoms. The
      remaining six patients were closely observed with conservative measures, with
      only one patient who showed resolution of the cyst.

PMID- 27879156
TI  - Enhancing tablet disintegration characteristics of a highly water-soluble high
      drug-loading formulation by granulation process.
AB  - The objective of this study was to improve the disintegration and dissolution
      characteristics of a highly water-soluble tablet matrix by altering the
      manufacturing process. A high disintegration time along with high dependence of
      the disintegration time on tablet hardness was observed for a high drug loading
      (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process.
      Keeping the formulation composition mostly constant, a fluid-bed granulation
      (FBG) process was explored as an alternate granulation method using a 2(4-1)
      fractional factorial design with two center points. FBG batches (10 batches) were
      manufactured using varying disingtegrant amount, spray rate, inlet temperature
      (T) and atomization air pressure. The resultant final blend particle size was
      affected significantly by spray rate (p = .0009), inlet T (p = .0062),
      atomization air pressure (p = .0134) and the interaction effect between inlet
      T*spray rate (p = .0241). The compactibility of the final blend was affected
      significantly by disintegrant amount (p < .0001), atomization air pressure (p =
      .0013) and spray rate (p = .05). It was observed that the fluid-bed batches gave
      significantly lower disintegration times than the HSWG batches, and mercury
      intrusion porosimetry data revealed that this was caused by the higher internal
      pore structure of tablets manufactured using the FBG batches.

PMID- 27879155
TI  - Managing cognition in progressive supranuclear palsy.
AB  - Cognitive impairment is integral to the syndrome of progressive supranuclear
      palsy. It is most commonly described as a frontal dysexecutive syndrome but other
      impairments include apathy, impulsivity, visuospatial and memory functions.
      Cognitive dysfunction may be exacerbated by mood disturbance, medication and
      communication problems. In this review we advocate an individualized approach to
      managing cognitive impairment in progressive supranuclear palsy with the
      education of caregivers as a central component. Specific cognitive and behavioral
      treatments are complemented by treatment of mood disturbances, rationalizing
      medications and a patient-centered approach to communication. This aims to
      improve patients' quality of life, reduce carer burden and assist people with
      progressive supranuclear palsy in decisions about their life and health,
      including discussions of feeding and end-of-life issues.

PMID- 27879158
TI  - Potential of lysophosphatidylinositol as a prognostic indicator of cardiac arrest
      using a rat model.
AB  - AIMS: The potential of a lysophosphatidylinositol species, LPI(18:0), as a
      biomarker of ischaemia was tested using a rat model of cardiac arrest (CA).
      METHODS: Male Sprague-Dawley rats were subjected to asphyxia-induced CA or CA
      followed by cardiopulmonary bypass (CPB) resuscitation. The brain, heart, kidney
      and liver tissues were harvested from rats after 0, 5, 10, 20, 30 and 60 min CA
      and 30 min CA followed by 60 min CPB resuscitation. Blood samples were collected
      from inferior vena cava and hepatic veins following 30 min CA. Phospholipids were
      extracted from the four tissues and blood and analysed by HPLC-MS. RESULTS: The
      relative content of LPI(18:0) compared to a phosphatidylinositol species,
      PI(18:0,22:4), was significantly increased in the brain, heart, liver and kidney
      following 30 min CA and decreased following CPB resuscitation. In addition, the
      increase of the LPI(18:0)/PI(18:0,22:4) ratio in the four tissues was
      proportional to the duration of ischaemia for CA lasting up to 60 min. The ratio
      was also found to be increased in plasma from the hepatic vein following 30 min
      CA. CONCLUSION: LPI(18:0) is a good indicator of CA downtime and has a potential
      to be used for early prognostication of outcome in CA.

PMID- 27879159
TI  - Poor interexaminer agreement on Friedman tongue position.
AB  - CONCLUSION: The Friedman tongue position demonstrated only a slight inter
      examiner agreement among 15 medical doctors, indicating that the method is
      difficult to perform and could be an uncertain method to select patients for
      uvulopalatopharyngoplasty. OBJECTIVE: The Friedman staging system is a clinical
      tool for selecting patients with obstructive sleep apnea who are appropriate for
      uvulopalatopharyngoplasty. The objective of this study was to evaluate the
      staging system by determining the inter-examiner agreement of one of its key
      components, the Friedman tongue position. METHODS: Eleven residents and four
      specialists in Otorhinolaryngology were recruited from a course in surgical
      management of obstructive sleep apnea. They examined each other's tongue
      positions, resulting in a total of 210 evaluations. Cohen's kappa analysis was
      performed to assess the inter-examiner agreement. The range of kappa is usually
      between 0-1, where 0 is complete disagreement and 1 is complete agreement.
      RESULTS: The median kappa was 0.36 (1st and 3rd quartile, 0.23 and 0.42),
      corresponding to only a slight agreement.

PMID- 27879161
TI  - Neopterin and oxidative stress markers in the diagnosis of extrapulmonary
      tuberculosis.
AB  - BACKGROUND: Extrapulmonary tuberculosis (EPTB) often presents with nonspecific
      signs and symptoms. Further the paucibacillary nature of extrapulmonary specimens
      and irregular distribution of bacilli lower the sensitivity of conventional
      diagnostic methods making EPTB, a diagnostic dilemma. OBJECTIVE: To study
      neopterin, protein carbonyl and malondialdehyde (MDA) in EPTB. METHODS: Sixty
      nine clinically confirmed cases with an equal number of age and sex matched
      healthy controls were enrolled. Ziehl-Neelsen staining for acid fast bacilli and
      culture on Lowenstein-Jensen medium were performed on all the extrapulmonary
      specimens. Serum neopterin and protein carbonyl levels were estimated using
      commercial ELISA kits. Malondialdehyde was determined by measuring thiobarbituric
      acid reactive substances. RESULTS: Serum neopterin, protein carbonyl and MDA
      levels were significantly discriminative for cases of EPTB from healthy controls
      (p < 0.05). Levels of all the three biomarkers under study significantly differed
      between culture as well as smear positive and negative cases. A positive
      correlation between neopterin and protein carbonyl was seen among the cases.
      CONCLUSIONS: So far few studies have integrated combination of validated host
      biomarkers for active disease in EPTB. Our study suggests the potential
      diagnostic role of neopterin, protein carbonyl and MDA in EPTB.

PMID- 27879160
TI  - Development of mannose-anchored thiolated amphotericin B nanocarriers for
      treatment of visceral leishmaniasis.
AB  - AIM: Our goal was to improve treatment outcomes for visceral leishmaniasis by
      designing nanocarriers that improve drug biodistribution and half-life. Thus,
      long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier
      complexes (MTC AmB) were developed and characterized. MATERIALS & METHODS: A
      mannose-anchored thiolated chitosan nanocarrier was manufactured and
      characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake
      and antimicrobial activities. RESULTS: MTC AmB was rod shaped with a size of 362
      nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug
      uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02
      MUg/ml compared with 0.26 MUg/ml for native drug. CONCLUSION: These studies show
      that MTC can serve as a platform for clearance of Leishmania in macrophages.

PMID- 27879163
TI  - A study of critical functionality-related characteristics of HPMC for sustained
      release tablets.
AB  - The drug release profile from hydrophilic matrix tablets can be crucially
      affected by the variability of physicochemical properties of the controlled
      release agent. This study investigates and seeks to understand the functionality
      related characteristics (FRCs) of hydroxypropyl methylcellulose (HPMC) type 2208,
      K4M grade, that influence the release rate of the model drug carvedilol from
      hydrophilic matrix tablets during the entire dissolution profile. The following
      FRCs were examined: particle size distribution, degree of substitution, and
      viscosity. Eight different HPMC samples were used to create a suitable design
      space. Multiple linear regression (MLR) and partial least squares regression
      (PLSR) analyses were used to create models for each time point. The PLSR results
      show that the first part of the drug release profiles is mainly regulated by the
      HPMC particle size. Apparent viscosity and hydroxypropoxy content (%HP) become
      important in later stages of the drug release profile, when the influence of
      particle size distribution decreases. These findings make it possible to better
      understand the importance of FRCs. Larger HPMC particles increase drug release in
      the first part of the drug release profile, whereas decreased apparent viscosity
      and a higher degree of %HP increase the drug release rate in the later part of
      the drug release profile.

PMID- 27879162
TI  - Polyanion-tobramycin nanocomplexes into functional microparticles for the
      treatment of Pseudomonas aeruginosa infections in cystic fibrosis.
AB  - AIM: Efficacy of antibiotics in cystic fibrosis (CF) is compromised by the poor
      penetration through mucus barrier. This work proposes a new 'nano-into-micro'
      approach, used to obtain a combinatorial effect: achieve a sustained delivery of
      tobramycin and overcome mucus barrier. METHODS: Mannitol microparticles (MPs)
      were loaded with a tobramycin polymeric nanocomplex and characterized in presence
      of CF artificial mucus. RESULTS & DISCUSSION: MPs are able to alter the
      rheological properties of CF artificial mucus, enhancing drug penetration into it
      and allowing a prolonged drug release. MPs resulted to be effective in
      Pseudomonas aeruginosa infections if compared with free tobramycin. CONCLUSION:
      MPs resulted to be a formulation of higher efficacy, with potential positive
      implications, as lower required dose, administration frequency, side effects and
      antibiotic resistance problems.

PMID- 27879164
TI  - What is most relevant in preoperative rectal cancer chemoradiotherapy - the
      chemotherapy, the radiation dose or the timing to surgery?

PMID- 27879165
TI  - EAHFE - TROPICA2 study. Prognostic value of troponin in patients with acute heart
      failure treated in Spanish hospital emergency departments.
AB  - OBJECTIVE: Evaluate the use of different cardiac troponin (cTn) immunoassays and
      the prognostic value of increased cTn values in patients diagnosed with acute
      heart failure (AHF) in the emergency department (ED). METHOD: The epidemiology
      acute heart failure emergency-TROPonin in acute heart failure2 (EAHFE-TROPICA2)
      is a retrospective study including patients with AHF admitted in 34 Spanish EDs
      with cTn values determined in the ED. We studied the prevalence of elevated
      troponin (value above the established reference limit) for the different types of
      troponin. We also assessed crude and adjusted primary (1-year all-cause death)
      and secondary (30 d ED revisit due to AHF) outcomes for every type of cTn and
      different magnitudes of troponin elevation. RESULTS: We analysed 4705 episodes of
      AHF. Troponin was elevated in 48.4% of the cases (25.3% in cTnI, 37.9% in cTnT
      and 82.2% in hs-cTnT). Mortality at one year was higher in patients with elevated
      troponin (adjusted HR 1.61; CI 95% 1.38-1.88) regardless of the type of cTn
      determined. Elevated troponin was not related to ED revisit within 30 d after
      discharge (1.01; 0.87-1.19). CONCLUSIONS: The use of conventional troponin in the
      ED is useful to predict one-year mortality in patients with AHF. Highly sensitive
      cTnT (hs-cTnT) elevations less than double the reference value have no impact on
      patient outcome.

PMID- 27879167
TI  - Rapid detection of TiO2 (E171) in table sugar using Raman spectroscopy.
AB  - The potential toxic effects of titanium dioxide (TiO2) to humans remain debatable
      despite its broad application as a food additive. Thus, confirmation of the
      existence of TiO2 particles in food matrices and subsequently quantifying them
      are becoming increasingly critical. This study developed a facile, rapid (< 30
      min) and highly reliable method to detect and quantify TiO2 particles (E171) from
      food products (e.g., table sugar) by Raman spectroscopy. To detect TiO2 particles
      from sugar solution, sequential centrifugation and washing procedures were
      effectively applied to separate and recover 97% of TiO2 particles from the sugar
      solution. The peak intensity of TiO2 sensitively responded to the concentration
      of TiO2 with a limit of detection (LOD) of 0.073 mg kg-1. In the case of sugar
      granules, a mapping technique was applied to directly estimate the level of TiO2,
      which can be potentially used for rapid online monitoring. The plot of averaged
      intensity to TiO2 concentration in the sugar granules exhibited a good linear
      relationship in the wide range of 5-2000 mg kg-1, with an LOD of 8.46 mg kg-1.
      Additionally, we applied Raman spectroscopy to prove the presence of TiO2 in
      sugar-coated doughnuts. This study begins to fill in the analytical gaps that
      exist regarding the rapid detection and quantification of TiO2 in food, which
      facilitate the risk assessment of TiO2 through food exposure.

PMID- 27879166
TI  - Sex differences in release of cardiac troponin T after endurance exercise.
AB  - CONTEXT: Post-exercise cardiac troponin release has been extensively described in
      athletic groups but little attention has been given to any role of sex in
      mediating this phenomenon. OBJECTIVE: We compared the release of cardiac troponin
      T (cTnT) after endurance running in training-experience, biological-age and
      maturity-matched young male and female runners. MATERIALS AND METHODS: Nineteen
      male (training history: 2.3 +/- 1.0 years; mean age: 16.1 +/- 1.2 years; Tanner
      stage: 3.7 +/- 0.6) and 19 female (training history: 2.2 +/- 1.0 years; mean age:
      15.9 +/- 1.4 years; Tanner stage: 4.0 +/- 0.4) runners performed a 21 km run with
      "all-out" effort. Serum cTnT levels were assessed at pre-exercise (Pre-ex) and at
      4 h post-exercise (Post-ex). RESULTS: At Pre-ex, cTnT concentrations were below
      the 99th percentile value (10 ng.l-1) in 32/38 runners. Post-ex cTnT increased in
      all subjects but the response was substantially higher (p < 0.05) in males
      [median (range): 210 (20-1360) ng.l-1] than females [median (range): 80 (10-550)
      ng.l-1]. At Post-ex, 95% (95% confidence interval: 75-99%) of males and 63% (95%
      confidence interval: 41-81%) of females (p < 0.05) had cTnT concentrations above
      the cut-off for acute myocardial infarction. CONCLUSIONS: The present data
      suggest that post-exercise cTnT elevation occurs in all runners but is augmented
      in young male compared to female athletes.

PMID- 27879168
TI  - Situation criticality and basketball officials' stress levels.
AB  - Officials are expected to perform impeccably despite the wide range of stressors
      they experience. A stressor that officials frequently report is situation
      criticality. Situation criticality is comprised of score differential (i.e., more
      pressure in close games) and time remaining in a game (i.e., more pressure as
      time expires), which affects athletes' stress levels. The present study explored
      the effect of situation criticality on officials' stress levels. High school
      basketball officials (n = 108) with an average of 18.1 (SD = 11.2) years of
      officiating experience were given a survey packet containing game situations that
      varied in criticality. For each game situation (n = 9) officials completed the
      overall stress and appraisal portions of the Stress Appraisal Measure (SAM).
      Results revealed that situation criticality has an effect on officials' perceived
      stress levels. Both threat and challenge appraisals were positively correlated
      with perceived stress. Overall, these findings indicate that officials' stress
      levels fluctuate within games depending on score differential and time of game.
      The findings encourage officials to recognise and manage their stress, possibly
      through their appraisals. Additionally, the findings can affect the training of
      officials in the management of stress, as well as prompt the consideration of
      potential rule changes that reflect the increased situational demands on
      officials in critical situations (e.g., expanded instant replay).

PMID- 27879169
TI  - Goal orientation and well-being in college athletes: The importance of athletic
      social connectedness.
AB  - The present study examined the ability of an interpersonal construct called
      athletic connectedness to mediate the relationship between task and ego goal
      orientations and well-being. We operationalised athletic social connectedness as
      a sense of social belonging and sense of connection with teammates. We
      hypothesised that athletic social connectedness would be positively associated
      with task goals, negatively associated with ego goals, and would at least
      partially mediate the relationship between achievement goals and well-being. We
      administered questionnaires to female (N = 106; mean age = 20.47, SD = 1.12) and
      male (N = 100; mean age = 20.95, SD = 1.21) NCAA Division III college athletes.
      We tested our hypothesised model using structural equation modelling, which
      included testing a measurement model that specified four latent variables and
      then comparing the estimates generated by our hypothesised model with our data.
      We also tested three alternative models and found our hypothesised model to fit
      best. As predicted, there were significant indirect effects of task and ego
      motivation on well-being through athletic connectedness, demonstrating formal
      evidence of mediation. The r2 coefficient indicated that the model explained 30%
      of the variance in well-being, a moderate effect size (Cohen, 1988). Discussion
      focuses on the importance of considering interpersonal constructs as a way to
      improve our understanding of relationship between task and ego goal orientations
      to well-being in athletes.

PMID- 27879171
TI  - Detection and quantification of adulterants in milk powder using a high
      throughput Raman chemical imaging technique.
AB  - Milk is a vulnerable target for economically motivated adulteration. In this
      study, a line-scan high-throughput Raman imaging system was used to authenticate
      milk powder. A 5 W 785 nm line laser (240 mm long and 1 mm wide) was used as a
      Raman excitation source. The system was used to acquire hyperspectral Raman
      images in a wave number range of 103-2881 cm-1 from the skimmed milk powder mixed
      with two nitrogen-rich adulterants (i.e., melamine and urea) at eight
      concentrations (w/w) from 50 to 10,000 ppm. The powdered samples were put in
      sample holders with a surface area of 150 *100 mm and a depth of 2 mm for push
      broom image acquisition. Varying fluorescence signals from the milk powder were
      removed using a correction method based on adaptive iteratively reweighted
      penalised least squares. Image classifications were conducted using a simple
      thresholding method applied to single-band fluorescence-corrected images at
      unique Raman peaks selected for melamine (673 cm-1) and urea (1009 cm-1).
      Chemical images were generated by combining individual binary images of melamine
      and urea to visualise identification, spatial distribution and morphological
      features of the two adulterant particles in the milk powder. Limits of detection
      for both melamine and urea were estimated in the order of 50 ppm. High
      correlations were found between pixel concentrations (i.e., percentages of the
      adulterant pixels in the chemical images) and mass concentrations of melamine and
      urea, demonstrating the potential of the high-throughput Raman chemical imaging
      method for the detection and quantification of adulterants in the milk powder.

PMID- 27879170
TI  - The past, present and future of ligament regenerative engineering.
AB  - Regenerative engineering has been defined as the convergence of Advanced
      Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and
      Clinical Translation for the regeneration of complex tissues and organ systems.
      Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of
      bone, ligament and their interface to achieve superior clinical results. In the
      past, the ACL has been repaired with the use of autologous and allogeneic grafts,
      which have their respective drawbacks. Currently, investigations on the use of
      biodegradable matrices to achieve knee stability and permit tissue regeneration
      are making promising advancements. In the future, utilizing regenerative biology
      cues to induce an endogenous regenerative response may aid the enhancement of
      clinical ACL reconstruction outcomes.

PMID- 27879172
TI  - Polychlorobiphenyls in freshwater fish: a new strategy to set maximum
      contamination limits.
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants accumulating
      along the food chain, and particularly in fish. Consequently, the European
      Commission has set regulatory limits for PCBs in both sea- and freshwater fish.
      Focusing on freshwater fish, the French Agency for Food Environmental and
      Occupational Health & Safety has developed a method to determine the areas in
      France where the consumption of locally caught freshwater fish is not recommended
      due to PCB contamination. To determine these areas of potential health concern,
      an existing statistical model of the relationship between the consumption of
      local fish by freshwater anglers and their PCB body burden is linked to a newly
      determined critical PCB body burden threshold for the population. The main
      conclusions of this study are that the consumption of two freshwater fish per
      week from rivers in the areas of France where the median contamination level in
      fish is greater than 250 ng g-1 could lead to some exceedance of the critical
      body burden threshold.

PMID- 27879173
TI  - Residue depletion of oxytetracycline (OTC) and 4-epi-oxytetracycline (4-epi-OTC)
      in broiler chicken's claws by liquid chromatography-tandem mass spectrometry (LC
      MS/MS).
AB  - Antibiotics are widely used in poultry production for the treatment of bacterial
      diseases. However, residues may remain in products and by-products destined for
      human consumption or animal feeding. The claws of chickens, which are a by
      product of the poultry industry, can directly or indirectly enter the food chain
      as meals destined to feed other productive animals. Thus, it becomes necessary to
      determine and quantify antimicrobial residues present in this matrix. The
      objective of the study was to assess the depletion of oxytetracycline (OTC) and
      its metabolite 4-epi-OTC in broiler chicken's claws. Claws of 32 broilers treated
      with a therapeutic dosage of 10% OTC during 7 days were analysed. Samples were
      taken at days 3, 9, 15 and 19 post-treatment. As for the control group, eight
      broiler chickens were raised under the same conditions. Extraction was carried
      out through EDTA-McIlvaine buffer, and clean-up employed a SPE C-18 Sep-Pak(r).
      Instrumental analysis was performed through LC-MS/MS. The concentrations of both
      analytes were determined in claw samples until day 19 post-treatment. Average
      concentrations were within the LOD (20 MUg kg-1) and LOQ (22 ug kg-1) for OTC and
      84 MUg kg-1 for 4-epi-OTC. Withdrawal times (WDTs) of 39 days for OTC and 54 days
      for 4-epi-OTC were established in claws based on 95% confidence. These findings
      demonstrate that claws can be a source of antimicrobial residue entry into the
      food chain, since the results showed that OTC and its metabolite can be found in
      chicken's claws for long periods, even exceeding the average lifespan of a
      broiler chicken.

PMID- 27879174
TI  - Determination of sub-ng g-1 levels of total inorganic arsenic and selenium in
      foods by hydride-generation atomic absorption spectrometry after pre
      concentration.
AB  - A new and simple ultrasonic-assisted extraction (UAE) procedure was developed for
      the determination of inorganic arsenic and selenium in foods by hydride
      generation atomic absorption spectrometry (HG-AAS). The various analytical
      variables affecting complex formation and extraction efficiency were investigated
      and optimised. The method is based on selective complex formation of As(III) and
      Se(IV) in the presence of excess As(V) and Se(VI) with toluidine red in the
      presence of tartaric acid at pH 4.5, and then extraction of the resulting
      condensation products into the micellar phase of non-ionic surfactant,
      polyethylene glycol dodecyl ether, Brij 35. Under optimised conditions, good
      linear relationships were obtained in the ranges of 4-225 and 12-400 ng l-1 with
      limits of detection of 1.1 and 3.5 ng l-1 for As(III) and Se(IV), respectively.
      The repeatability was better than 3.9% for both analytes (n = 10, 25 ng l-1)
      while reproducibility ranged from 4.2% to 4.8%. The recoveries of As(III) and
      Se(IV) spiked at 25-100 ng l-1 were in the range of 94.2-104.8%. After pre
      concentration of a 5.0 ml sample, the sensitivity enhancement factors for As(III)
      and Se(IV) were 185 and 140, respectively. Accuracy was assessed by analysis of
      two standard reference materials (SRMs) and spiked recovery experiments. The
      method was successfully applied to the accurate and reliable determination of
      total As and total Se by HG-AAS after pre-reduction with a mixture of L-cysteine
      and tartaric acid. Finally, the method was shown to be rapid and sensitive, with
      good results for extraction, pre-concentration and determination of total As and
      Se contents (as As(III) and Se(IV)) from food samples.

PMID- 27879175
TI  - Identifying talented track and field athletes: The impact of relative age effect
      on selection to the Spanish National Athletics Federation training camps.
AB  - This study examined the impact of relative age effect (RAE) on selection to the
      Spanish National Athletics Federation (RFEA) training camps (TC) between 2006 and
      2013. Overall, 1,334 selected athletes at U15 years (cadet) and U17 years
      (juvenile) were compared against 27,711 licensed but unselected athletes for the
      same age groups. The results highlighted the influential role of the RAE on
      selection to national level track and field training camp opportunities.
      Interestingly, this effect was mediated by age and gender, where effects were
      stronger for both males and younger athletes (U15), with no evidence of RAE for
      older (U17) female athletes. These results support the "maturation-selection"
      hypothesis as a mechanism for RAE. Particularly given the long-term goals of RFEA
      (e.g., production of successful senior elite athletes), these results highlight
      the need to consider the impact of current selection processes on effective
      provision of opportunities to those athletes with most potential to succeed in
      the long term. A number of possible context-relevant solutions are discussed,
      including education and awareness raising, using holistic selection criteria and
      correction adjustments techniques.

PMID- 27879176
TI  - Focus-of-attention behavioral experiment: an examination of a therapeutic
      procedure to reduce social anxiety.
AB  - A clinical protocol based on contemporary cognitive behavioral treatment for
      social anxiety was developed and examined. Previously published instructions for
      conducting a focus-of-attention behavioral experiment targeting self-focused
      attention and safety behaviors during exposure were used to create a structured
      protocol. Individuals (n = 45) with high levels of social anxiety and public
      speaking anxiety were randomly assigned to either a focus-of-attention behavioral
      experiment (FABE) or an Exposure-Only Control (EOC) condition. During four
      exposure trials, those in the FABE condition (n = 24) were alternately instructed
      to engage in self-focused attention vs. externally focused attention and to
      eliminate safety behaviors. Those in the EOC condition (n = 21) were not so
      instructed. At post-intervention, individuals in the FABE condition showed
      significantly less self-focused attention and anxiety, and better observed
      performance as rated by audience members. Focus-of-attention statistically
      mediated the effect of condition on anxiety. For those in the FABE condition, the
      degree of association between focus-of-attention and anxiety during the
      intervention predicted less self-focused attention post-intervention. The FABE
      appears to be a useful procedure for implementing part of the contemporary
      cognitive behavioral treatment model.

PMID- 27879177
TI  - [Retinal haemorrhages as a symptom of child abuse].
AB  - Inflicted traumatic brain injury (ITBI) - a possible result of child abuse - is
      difficult to diagnose, yet the diagnosis bears great impact on patients and their
      relatives. The purpose of this paper is to describe ophthalmologic findings that
      can be seen in relation to ITBI. For exemplification, three different cases are
      described in detail. ITBI is diagnosed through a multidisciplinary approach by
      exclusion of other causes that could explain the clinical findings, and by
      linking factors that together raise a high suspicion of ITBI. The typical triad
      of ITBI includes intracerebral haemorrhage, encephalopathy and retinal
      haemorrhages. Therefore, detailed fundus examination by an ophthalmologist is
      important when ITBI is suspected. A pattern of bilateral, multiple retinal
      haemorrhages present in different retinal layers and widespread from posterior
      pole to the retinal periphery, is highly suspicious for ITBI, and contributes to
      the final diagnosis.

PMID- 27879178
TI  - [Minocycline-induced hyperpigmentation: not uncommon, but nonetheless important
      to recognise].
AB  - BACKGROUND: Minocycline, a broad-spectrum antibiotic from the group of
      tetracyclins, is frequently prescribed for acne vulgaris and rosacea.
      Hyperpigmentation is a relatively common side effect of this drug and can lead to
      multiple unsightly skin lesions, which are not always reversible. It can take a
      long period, from a few months to several years, before the lesions have
      completely vanished. CASE DESCRIPTION: A 24-year-old male was seen in our
      outpatient clinic because of slowly progressive pigmented lesions on his shins.
      His medical history included chronic use of minocycline for the treatment of acne
      vulgaris. Based on the morphology of the lesions, the patient's medical history
      and analysis of a skin biopsy, the diagnosis 'minocycline-induced
      hyperpigmentation type 2'was made. CONCLUSION: Hyperpigmentation is a relatively
      common and undesirable side-effect of minocycline use. Long-term prescription of
      this drug for more than one year should therefore be considered with caution,
      especially if the dose exceeds 100 milligrams per day.

PMID- 27879179
TI  - [Two sisters with lung emphysema].
AB  - BACKGROUND: alpha1-antitrypsin is an antiprotease that is mainly produced in the
      liver; it plays a crucial role in the protection of lung parenchyma against the
      destructive effects of proteases. Mutations in the alpha1-antitrypsin gene can
      cause alpha1-antitrypsin deficiency. Individuals homozygous for the Z-genotype
      have drastically lowered serum alpha1-antitrypsine concentrations and often
      develop lung emphysema at an early age. CASE DESCRIPTION: A 38-year-old woman and
      her 43-year-old sister both developed lung emphysema at an early age; this could
      be attributed to severe alpha1-antitrypsin deficiency. The only treatment for
      this condition is alpha1-antitrypsin supplement therapy, but this therapy is not
      reimbursed by health insurance companies in the Netherlands. CONCLUSION: alpha1
      antitrypsin deficiency is a relatively rare cause of lung emphysema and can be
      seen as an orphan phenotype of chronic obstructive pulmonary disease (COPD). We
      appeal for reconsideration of coverage of alpha1-antitrypsine supplement therapy
      by basic health insurance in the Netherlands, on the basis of a recent randomised
      placebo-controlled study in which the protective effect of this therapy on
      progressive emphysema was demonstrated by CT lung densitometry.

PMID- 27879181
TI  - [Integral obstetrics impeded by history? Midwives and gynaecologists through the
      ages].
AB  - There is a long and complicated history concerning the interprofessional
      collaboration between midwives and gynaecologists, which is still evident in
      current practice. Yet, in the analysis of collaborative problems, history and its
      lessons are often overlooked. Consequently, less effective solutions to problems
      may be found, because the root cause of a problem is not addressed. In this
      historical perspective we show how policies of the respective professions have
      often focused on self-preservation and competition, rather than on effective
      collaboration. We also highlight how the independent midwives lost and regained
      authorisation, status and income. Finally, using a theoretical model for
      interprofessional collaboration, we reflect on where history impedes the
      development of integral obstetrics. The focus must be averted away from
      professional self-interest and power struggles, but this proves to be a complex
      exercise.

PMID- 27879180
TI  - [Web-based interventions targeting cardiovascular risk factors in older people; a
      systematic review and meta-analysis].
AB  - OBJECTIVE: To evaluate whether web-based interventions for cardiovascular risk
      factor management reduce the risk of cardiovascular disease in older people.
      DESIGN: Systematic review and meta-analysis. METHOD: Embase, Medline, Cochrane
      Library and CINAHL were systematically searched from January 1995 to 3 November
      2014. We included all randomised controlled trials for web-based interventions
      targeting cardiovascular risk factors in populations with a mean age of 50 and
      older. The outcome measures were cardiovascular risk factors (blood pressure,
      HbA1c, LDL cholesterol, weight, smoking status and physical activity) and the
      incidence of cardiovascular disease. We used random-effects models to pool the
      results of the studies. RESULTS: A total of 57 studies (19,862 participants)
      fulfilled eligibility criteria, and 47 of these were suitable for meta-analysis.
      We found a significant reduction in systolic blood pressure (-2.66 mmHg, 95% CI 
      3.81 to -1.52), diastolic blood pressure (-1.26 mmHg, 95% CI -1.92 to -0.60),
      HbA1c level (-0.13%, 95% CI -0.22 to -0.05), LDL cholesterol level (-0.06 mmol/l,
      95% CI -0.10 to -0.01), weight (-1.34 kg, 95% CI -1.91 to -0.77), and an increase
      in physical activity (standardized mean difference 0.25, 95% CI 0.10-0.39) in the
      intervention group when compared with the control group. Treatment effects were
      more pronounced in studies of short duration (< 12 months) and when combining the
      web-based intervention with human support by a health care professional. No
      difference in the incidence of cardiovascular disease was found between groups.
      CONCLUSION: Web-based interventions have a beneficial effect on the
      cardiovascular risk profile, but this effect is modest and declines with time.
      Currently, there is insufficient evidence that this can prevent cardiovascular
      disease. A focus on long-term effects, effect-sustainability and clinical
      endpoints is recommended for future studies.

PMID- 27879182
TI  - [Acute respiratory failure caused by minocycline].
AB  - BACKGROUND: In the case of pneumonia an infectious cause is always considered
      first. However, toxic agents and medicines can also be the cause of pneumonia.
      CASE DESCRIPTION: A 54-year-old woman was referred to the emergency department
      because of progressive dyspnoea, a non-productive cough, headache, and fever. She
      was admitted with the diagnosis community acquired pneumonia. Despite treatment
      with antibiotics and oxygen she developed hypoxic respiratory failure, which
      necessitated invasive mechanical ventilation. Imaging diagnostics showed
      extensive bilateral pulmonary consolidation, despite the absence of a causative
      agent in cultures. Further medical history-taking revealed that the patient had
      recently commenced a course of minocycline. She had used this medicine previously
      and had twice before developed pneumonia without the presence of a proven
      causative agent. Our differential diagnosis included the toxic effect of
      minocycline and we treated the patient with methylprednisolone. This resulted in
      rapid clinical improvement and full recovery of our patient. CONCLUSION: Acute
      respiratory failure as a side effect of medication is rare, but nonetheless
      potentially life-threatening. Despite repeated exposure to minocycline, the link
      with pneumonia was not previously made in this patient.

PMID- 27879183
TI  - [Supporting patients in self-management: moving to a personalised approach].
AB  - OBJECTIVE: The aim of this research was to assess the effect of providing
      personalised self-management support on patient activation (knowledge, skills,
      self-efficacy) and self-management behaviour. DESIGN: Cluster randomised trial in
      15 general practices (Dutch Trial Register No.: NTR 3960). METHOD: Patients aged
      18 years or older with a chronic condition were invited to participate in the
      study. The Self-Management Screening (SeMaS) questionnaire - which illustrates
      barriers to self-management - was used as a tool for personalised self-management
      support. Nurse practitioners in the intervention practices were trained for 2
      hours in using SeMaS and personalising self-management support on the basis of
      the SeMaS profile. At baseline and after 6 months, patients filled in
      questionnaires on patient activation (PAM-13) and lifestyle. Using data from the
      questionnaires and medical records, the use of individual care plans, referrals
      to self-management interventions, self-monitoring and healthcare use were
      assessed. We used a multiple multilevel regression model for data analysis.
      RESULTS: After 6 months, no difference was found in patient activation between
      the control group (n = 348) and the intervention group (n = 296). 29.4% of the
      patients in the intervention group performed self-monitoring, versus 15.2% in the
      control group (regression coefficient r = 0.9, p = 0.01). In the per-protocol
      analysis (control n = 348; intervention n = 136), the number of individual care
      plans (r = 1.3, p = 0.04) and the number of patients performing self-monitoring
      (r = 1.0; p = 0.01) were higher in the intervention group. CONCLUSION:
      Personalised self-management support with the use of the SeMaS method stimulates
      self-monitoring and the use of individual care plans. The intervention had no
      effect on patient activation or lifestyle. Given the positive secondary outcomes,
      the further potential of the tool should be researched.

PMID- 27879184
TI  - [Myopia, a growing health problem].
AB  - - Myopia is the eye disorder with the most rapid increase in prevalence
      worldwide. It develops in childhood, with a peak incidence between the ages of 13
      to 15 years. - Especially high myopia, i.e. a refractive error of -6 diopters or
      more, increases the risk of permanent visual impairment during adulthood due to
      structural abnormalities of the retina and optic nerve.- The cause of myopia is
      complex. Lifestyle factors in childhood, such as limited time spent outdoors and
      close work - such as reading and smartphone usage - are risk factors.
      Furthermore, genetic studies have revealed more than 100 factors associated with
      the development of myopia. - Pharmacological and optical interventions to inhibit
      myopia progression are increasingly applied. The use of atropine eye drops in
      children and has shown to be an effective treatment.

PMID- 27879185
TI  - [An integrated approach including paediatric and forensic medical expertise on
      suspicion of child abuse].
AB  - A false accusation of child abuse has a major impact on child and family.
      Conversely, a missed diagnosis of child abuse may have significant and lifelong
      consequences for the child. For health professionals the assessment of the nature
      of the injury and differentiating between accidental and inflicted injury,
      disease manifestation or a physiological phenomenon can be challenging. For
      adequate determination of the cause of injury, an integrated approach including
      paediatric knowledge and forensic medical expertise is essential. Therefore, a
      national expertise centre for child abuse (LECK) was established in the
      Netherlands in 2014. The first results of this integrated approach are described
      and illustrated with three case reports. Case A, a 7-month-old boy with an
      accidental humerus fracture. Case B, an 8-year-old boy with a false positive
      suspicion of child abuse who was eventually diagnosed with Henoch-Schonlein
      syndrome. Case C, boy of 3 months with bruises and a metaphyseal fracture of the
      femur, both highly suspected of being inflicted injury.

PMID- 27879186
TI  - [To reimburse or not? Evaluating expensive drugs differently].
AB  - Health insurance organisations grant reimbursement for drug treatment on the
      basis of results of placebo-controlled randomised clinical trials showing a
      clinically meaningful and statistically significant effect over placebo. This
      often proves problematic in rare diseases as well as in many chronic diseases
      that are difficult to treat. Clinical scientists may address the issue by testing
      the drug on surrogate outcome parameters and ask for post-marketing studies
      conducted by expert reference centres as expediency research, using budgets
      provided by the government to show that the drug really works in terms of real
      life patient experience. In the past 5 years, the pharmaceutical industry has
      released an increasing number of expensive drugs for rare diseases; this
      jeopardises the solidarity of health insurance cover for all EU citizens. To
      facilitate drug development, a new model might benefit all key players involved.
      The foundation Fair Medicine recently called for coalitions that jointly develop
      medicines based on contribution and complementarity, sharing responsibilities,
      risks and rewards.

PMID- 27879188
TI  - The Sustainable Kidney Care Foundation's contribution to the improvement of AKI
      management in developing countries using peritoneal dialysis.
AB  - Professional organizations, such as kidney foundations, have been active for over
      half a century in the field of nephrology, serving as the basic institutions for
      advocacy, disease education, prevention, and treatment. These organizations have
      focused efforts in four areas: supporting the training of clinical specialists,
      raising awareness about kidney disease, improving patient outcomes, and
      organizing continuing medical education. These activities, while essential for
      the success of nephrology organizations, do not usually initiate renal service
      programs in the neediest of places. To remedy the lack of renal programs in many
      developing countries, the Sustainable Kidney Care Foundation (SKCF) was founded
      with the objective of establishing treatment programs for acute kidney injury
      (AKI) in areas of the world where none exist. Today SKCF is active in 5 sub
      Saharan African countries and is growing.

PMID- 27879187
TI  - Recent trends in primary-care antidepressant prescribing to children and young
      people: an e-cohort study.
AB  - BACKGROUND: Concerns relating to increased use of psychotropic medication
      contrast with those of under-treatment and under-recognition of common mental
      disorders in children and young people (CYP) across developed countries. Little
      is known about the indications recorded for antidepressant prescribing in primary
      care in CYP. METHOD: This was an electronic cohort study of routinely collected
      primary-care data from a population of 1.9 million, Wales, UK. Poisson regression
      was undertaken to model adjusted counts of recorded depression symptoms,
      diagnoses and antidepressant prescriptions. Associated indications were explored.
      RESULTS: 3 58 383 registered patients aged 6-18 years between 1 January 2003 and
      31 December 2013 provided a total of 19 20 338 person-years of follow-up. The
      adjusted incidence of antidepressant prescribing increased significantly
      [incidence rate ratio (IRR) for 2013 = 1.28], mainly in older adolescents. The
      majority of new antidepressant prescriptions were for citalopram. Recorded
      depression diagnoses showed a steady decline (IRR = 0.72) while depression
      symptoms (IRR = 2.41) increased. Just over half of new antidepressant
      prescriptions were associated with depression (diagnosis or symptoms). Other
      antidepressant prescribing, largely unlicensed, was associated with diagnoses
      such as anxiety and pain. CONCLUSION: Antidepressant prescribing is increasing in
      CYP while recorded depression diagnoses decline. Unlicensed citalopram
      prescribing occurs outside current guidelines, despite its known toxicity in
      overdose. Unlicensed antidepressant prescribing is associated with a wide range
      of diagnoses, and while accepted practice, is often not supported by safety and
      efficacy studies. New strategies to implement current guidance for the management
      of depression in CYP are required.

PMID- 27879189
TI  - Gemcitabine-induced hemolytic-uremic syndrome treated with eculizumab or
      plasmapheresis: two case reports?.
AB  - BACKGROUND: Drug-induced hemolytic-uremic syndrome (HUS) has shown good response
      to eculizumab (ECU). We present 2 cases of patients with gemcitabine-induced HUS
      (GEM-HUS), one of whom was treated with ECU and the other with conventional
      treatment. Patient 1: A 74-year-old male with resected adenocarcinoma of the
      pancreas started adjuvant treatment with GEM, but after 5 months GEM was
      discontinued due to acute kidney injury and severe hypertension. Laboratory
      analyses identified microangiopathic hemolytic anemia (MHA) and thrombocytopenia.
      Plasmapheresis (Pph) was initiated but was stopped due to a severe adverse
      reaction. Treatment with ECU was initiated at the time of clinical progression
      requiring hemodialysis. After 7 doses of ECU, hemolysis and kidney function
      improved and the patient was able to stop hemodialysis. 1 month after the last
      dose of ECU serum creatinine (sCr) was 1.8 mg/dL. Patient 2: A 68-year-old male
      with resected urothelial carcinoma stopped GEM after 2 months due to hematologic
      toxicity. 1 month later the patient visited the emergency room due to minimal
      effort dyspnea, hypertension, and peripheral edema. Laboratory analyses showed
      decreased kidney function, MHA, and thrombocytopenia. Symptomatic treatment was
      started. After an initial recovery, kidney dysfunction, hemolysis, and
      thrombocytopenia progressed. Corticoid boluses were ineffective and hemodialysis
      was initiated. Eleven Pph treatments were necessary to recover hematologic data.
      The patient remained on hemodialysis for 2 months and evolved to stage IV chronic
      kidney disease. 8 months after hospital release, sCr was 3.5 mg/dL. CONCLUSION:
      ECU successfully improved kidney function in a patient with GEM-HUS, while
      conventional treatment did not.?.

PMID- 27879190
TI  - Transplantation in Africa - an overview.
AB  - Africa is underdeveloped in terms of treatment options for patients with end
      stage renal failure. Economic growth and corresponding increases in health
      expenditures in the African region mean that we can confidently anticipate
      increased demand for organ transplantation within the region over the next few
      years. Renal failure in Africa occurs mainly due to glomerular nephropathies,
      hypertension, diabetes, and HIV. For the subset of the population that might be
      considered medically suitable for transplantation, demand for transplantation is
      tightly constrained by the availability of specialist physicians and surgeons,
      pathology facilities, capacity to achieve acceptable graft outcomes, cultural and
      religious attitudes towards organ donation, trust in the health system, and the
      extent to which patients are able to meet the costs of surgery and ongoing
      immunosuppression. There are currently several countries in Africa which are
      building up living-related-donor transplantation. Active living-donor
      transplantation already takes place in South Africa, Tunisia, and Sudan, but
      deceased donation is only available in South Africa. Whereas living-donor
      transplantation might be successfully driven by a motivated individual and a
      single institution, deceased-donor transplantation requires dialysis programs,
      tissue typing and crossmatching facilities, an organ procurement program, an on
      call surgical team, capacity to fund this infrastructure, and an appropriate
      legislative framework. A significant and recurring barrier to transplantation in
      the African region is the high cost of transplantation and follow-up care, and,
      in particular, the cost of maintenance immunosuppression. A positive environment
      that could potentially change this scenario will have to include governmental
      funding, academic support to clinicians as well as a legislative framework, which
      is still needed in many African countries.

PMID- 27879191
TI  - Replacement of SFC-DPI with SFC-MDI exhaled through the nose improves
      eosinophilic chronic rhinosinusitis in patients with bronchial asthma.
AB  - OBJECTIVE: Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic
      rhinosinusitis with nasal polyps, is a refractory disease closely associated with
      bronchial asthma. We recently reported on the efficacy of ultra-fine particle
      inhaled corticosteroids (ICS) (hydrofluoroalkane-134a-beclomethasone
      dipropionate: HFA-BDP) exhalation through the nose (ETN) treatment for mild-to
      moderate asthmatics with ECRS. However, the effect of HFA-BDP ETN was found to be
      transient in some cases with severe ECRS and asthma, requiring treatment with
      higher-dose ICS and long-acting beta2-agonists (LABA). Here, we present a case of
      refractory ECRS with severe asthma treated with a combination of high-dose ICS
      and LABA ETN, and we discuss the mechanisms for its effectiveness. METHODS: A 57
      year-old man was treated with the combined regimen of HFA-BDP ETN and
      salmeterol/fluticasone combination (SFC) dry powder inhaler (DPI) for his
      refractory ECRS with severe asthma. For better control, we replaced SFC-DPI with
      SFC metered-dose inhaler (MDI) ETN and evaluated the clinical effect and
      corticosteroid sensitivity. We also examined the flow and deposition of fine
      particles released by SFC-MDI ETN. RESULTS: After switching to SFC-MDI ETN, the
      patient's conditions markedly resolved with the restoration of corticosteroid
      sensitivity and PP2A activity. The fine particles released by SFC-MDI ETN at
      least partially flowed out through the external nares and seemed to be deposited
      on the ethmoid sinus. CONCLUSION: Fine particle ICS/LABA ETN might be an
      additional therapeutic option for refractory ECRS with severe asthma and
      corticosteroid insensitivity.?.

PMID- 27879192
TI  - N-terminal probrain natriuretic peptide in patients with acute coronary
      syndrome?.
AB  - OBJECTIVE: To observe the changes and evaluate the significance of serum N
      terminal probrain natriuretic peptide (NT-proBNP) levels in patients with acute
      coronary syndrome and to discuss its clinical significance and relationship with
      the severity of disease. METHODS: Serum NT-proBNP levels were determined rapidly
      by using the triage BNP test for 98 consecutive patients with coronary heart
      disease (CAD) admitted to the hospital from March 2013 to December 2013; the
      correlation between the concentration of NT-proBNP and the degree of severity of
      the disease was analyzed. RESULTS: The levels of NT-proBNP in the acute
      myocardial infarction (AMI) group were higher compared with unstable angina
      pectoris (UAP), stable angina pectoris (SAP), and control groups, and the levels
      of NT-proBNP in UAP were higher compared to the SAP and control groups. Levels of
      NT-proBNP in the extensive anterior wall infarction group were higher compared to
      that of the inferior or anteroseptal wall infarction groups: p < 0.05; the levels
      of NT-proBNP in the inferior wall and posterior wall infarction group were higher
      compared with the inferior wall infarction group and anteroseptal wall infarction
      group: p < 0.05; the levels of NT-proBNP in the multi-vessel group were higher
      than those in the single-vessel group: p < 0.05. The BNP level was positively
      correlated with age, heart rate, creatinine kinase-myocardial band (CK-MB),
      cardiac troponin T (cTnT), and blood urea nitrogen (BUN), whereas it was
      negatively correlated with left ventricular ejection fraction (LVEF).
      CONCLUSIONS: NT-proBNP is related to the lowering of left ventricular ejection
      fraction and the severity of myocardial ischemia.?.

PMID- 27879194
TI  - Prescription patterns and drug costs in German patients with dementia in nursing
      homes and home-care settings?.
AB  - AIMS: To analyze prescription patterns and drug costs in German patients with
      dementia who are in home-care settings and nursing homes. METHODS: The present
      retrospective study based on the Disease Analyzer epidemiological database and
      included 41,064 patients treated by general practitioners (GPs) and 20,649
      patients treated by psychiatric practitioners (PPs), who were diagnosed with
      dementia in 2014. Four different types of antidementia therapy were included in
      the analysis. The shares of prescriptions and the associated costs in dementia
      patients in home-care settings and nursing homes were estimated. Regression
      analyses were performed to study the impact of the type of residence on the
      likelihood of receiving a defined therapy and incurring its associated cost.
      RESULTS: Antidementives were more frequently prescribed to patients in home-care
      settings, whereas antidepressants, antipsychotics, and benzodiazepines were more
      commonly administered to nursing-home patients in both the GP and the PP groups.
      Individuals residing in nursing homes had a lower likelihood of receiving
      antidementives but exhibited a higher likelihood of being prescribed
      antidepressants, antipsychotics, and benzodiazepines. The total cost of therapy
      was higher in nursing homes than in home-care settings (GPs: difference of ?
      27.20; PPs: difference of ? 107.90). The cost of antidementives was significantly
      lower in GP patients residing in nursing homes than in GP patients living at
      home. There was no significant difference in the cost of antidementives in the PP
      groups. By contrast, the costs of the three other families of drugs were lower in
      individuals cared for at home than in individuals residing in nursing homes, in
      both practice types. CONCLUSION: Prescription patterns and the drug costs in
      dementia patients significantly differed between home-care settings and nursing
      home settings.?.

PMID- 27879193
TI  - Pharmacokinetic comparison of two formulations of talniflumate 370 mg tablets in
      healthy Korean volunteers?.
AB  - BACKGROUND: Talniflumate, a prodrug of niflumic acid, is a potent analgesic and
      anti-inflammatory drug that has been widely used for the treatment of rheumatoid
      diseases. OBJECTIVE: The aim of this study was to compare the pharmacokinetics
      and to evaluate the bioequivalence of two formulations of talniflumate 370 mg
      tablets (test formulation: Flumagen<sup>(r)</sup> 370 mg tablet; reference
      formulation: Somalgen<sup>(r)</sup> 370 mg tablet). METHODS: A randomized, open
      label, single dose, two-sequence, two-period crossover clinical study was
      conducted. After oral administration of the study drug in each period, blood
      samples were collected up to 15 hours post-dose. The plasma concentration of
      niflumic acid, a metabolite of talniflumate, was determined using HPLC-MS/MS. The
      pharmacokinetic parameters were estimated by non-compartmental method. RESULTS:
      The maximum plasma concentration (Cmax) and area under the concentration-time
      curve from zero to the time point with the last measurable concentration
      (AUClast) for the test formulation were 290.7 +/- 199 ug/L and 1,154 +/- 643
      ug*h/L, respectively, and the corresponding values for the reference formulation
      were 286.8 +/- 193 ug/L and 1,151 +/- 577 ug*h/L, respectively. The geometric
      mean ratio and 90% confidence intervals (CI) of the test formulation to the
      reference formulation for the Cmax and -AUClast were 0.983 (0.829 - 1.166) and
      0.979 (0.856 - 1.121), respectively. CONCLUSIONS: The pharmacokinetic profiles of
      the test and reference formulations were found not to be significantly different,
      meeting the Korean regulatory criteria for bioequivalence.?.

PMID- 27879195
TI  - Pharmacokinetic comparison and bioequivalence evaluation of two 10-mg baclofen
      formulations in healthy male subjects?.
AB  - BACKGROUNDS: Baclofen is used as a skeletal muscle relaxant for multiple
      sclerosis patients. It depresses the transmission of monosynaptic and
      polysynaptic reflex by stimulating GABA<sub>beta</sub> (gamma-aminobutyric acid)
      receptors. OBJECTIVES: The aim of this study was to compare the pharmacokinetic
      characteristics of two 10-mg baclofen formulations and to assess bioequivalence.
      METHODS: A randomized, single-dose, two-period, two-sequence crossover study was
      conducted in healthy male subjects. Each subject received the test or reference
      formulations. After washout period, all subjects received the alternative
      formulation. Blood samples were collected for up to 24 hours after the dose in
      each period. Pharmacokinetic (PK) parameters, including t<sub>max</sub>,
      C<sub>max</sub>, and AUC<sub>last</sub> were calculated by noncompartmental
      methods. The geometric mean ratio (GMR) of the test to the reference formulation
      and its 90% confidence interval (CI) for C<sub>max</sub> and AUC<sub>last</sub>
      were calculated for assessment of bioequivalence. RESULTS: A total of 22 subjects
      completed the study. The median t<sub>max</sub> of the test and the reference
      formulation were 1.50 and 1.25 hours, respectively. The mean (+/- SD)
      C<sub>max</sub> of the test and the reference formulation were 141.401 +/- 29.447
      ng/mL and 138.837 +/- 31.392 ng/mL, respectively. The mean (+/- SD)
      AUC<sub>last</sub> of the two formulations were 702.404 +/- 82.149 ng*h/mL and
      726.803 +/- 90.638 ng*h/mL, respectively. The GMR (90% CI) of the test to the
      reference formulation for the C<sub>max</sub> and AUC<sub>last</sub> were 1.0306
      (0.9564 - 1.1106) and 0.9674 (0.9437 - 0.9916), respectively. CONCLUSIONS: The
      two different baclofen 10-mg formulations had similar PK profiles and were
      bioequivalent based on C<sub>max</sub> and AUC<sub>last</sub>.?.

PMID- 27879196
TI  - Treatment persistence in the use of basal insulins in Poland and Germany?.
AB  - AIMS: To compare short-term basal insulin therapy persistence and its predictors
      in Poland and Germany. METHODS: Persistence was defined as proportions of
      patients remaining on the initial basal insulin (analogs: Poland: n = 6,889,
      Germany: n = 454,067; neutral protamine Hagedorn (NPH) insulins: Poland: n =
      50,761, Germany: n = 226,064) over 2 years based on nationwide prescription
      databases (LRx; IMS Health) in Poland and Germany from 2013 to 2015. Persistence
      was evaluated by Kaplan-Meier curves (log-rank tests). Risk of discontinuation of
      initial basal insulin was investigated using Cox regression models adjusting for
      age, sex, comedication with other glucose-lowering agents and baseline or
      comedication with antihypertensives, lipid-lowering drugs, antidepressants, and
      antiepileptics. RESULTS: In Poland, 2-year persistence was 83.0% in analog
      insulin and 73.3% in NPH users (p < 0.001). In Germany, persistence was also
      higher in patients with analog insulins (92.6% vs. 79.0%; p < 0.001). Analog
      insulin users were less likely to discontinue basal insulin compared with NPH
      users (adjusted hazard ratio (95%CI): Poland: 0.73 (0.67 - 0.79); Germany: 0.27
      (0.27 - 0.28)). Higher age (> 75 vs. <= 60 years: Poland: 1.24 (1.16 - 1.33),
      Germany: 1.09 (1.07 - 1.11)) and GLP-1 receptor agonist use (Poland: 2.76 (1.38 -
      5.53), Germany: 1.21 (1.16 - 1.26)) were related to higher risk of
      discontinuation. Male sex, metformin, sulfonylurea, thiazolidinedione, and short
      acting insulin prescriptions as well as antihypertensive, anti-epileptic, and
      lipid-lowering drug use were associated with lower risk of discontinuation in
      both countries (all p < 0.05). CONCLUSIONS: This real-world study shows that both
      in Poland and Germany treatment persistence of newly-prescribed basal insulin is
      influenced by type of insulin (analog vs. NPH) and by glucose-lowering and other
      comedications.?.

PMID- 27879197
TI  - Pelvic Inflammatory Disease: Diagnosis And Treatment In The Emergency Department.
AB  - Pelvic inflammatory disease is a common disease that is associated with
      significant complications including infertility, chronic pelvic pain, ruptured
      tubo-ovarian abscess, and ectopic pregnancy. The diagnosis may be delayed when
      the presentation has nonspecific signs and symptoms. Even when it is properly
      identified, pelvic inflammatory disease is often treated suboptimally. This
      review provides evidence-based recommendations for the diagnosis, treatment,
      disposition, and follow-up of patients with pelvic inflammatory disease.
      Arranging follow-up of patients within 48 to 72 hours and providing clear patient
      education are fundamental to ensuring good patient outcomes. Emerging issues,
      including new pathogens and evolving resistance patterns among pelvic
      inflammatory disease pathogens are reviewed.

PMID- 27879198
TI  - Registered report: Coadministration of a tumor-penetrating peptide enhances the
      efficacy of cancer drugs.
AB  - The Reproducibility Project: Cancer Biology seeks to address growing concerns
      about reproducibility in scientific research by conducting replications of 50
      papers in the field of cancer biology published between 2010 and 2012. This
      Registered report describes the proposed replication plan of key experiments from
      'Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer
      drugs' by Sugahara and colleagues, published in Science in 2010 (Sugahara et al.,
      2010). The key experiments being replicated include Figure 2 and Supplemental
      Figure 9A. In Figure 2, Sugahara and colleagues presented data on the tumor
      penetrance of doxorubicin (DOX) when co-administered with the peptide iRGD, as
      well as the effect of co-treatment of DOX and iRGD on tumor weight and cell
      death. In Supplemental Figure 9A, they tracked body weight of mice treated with
      DOX and iRGD to provide evidence that iRGD does not increase known DOX toxicity.
      The Reproducibility Project: Cancer Biology is a collaboration between the Center
      for Open Science and Science Exchange, and the results of the replications will
      be published by eLife.

PMID- 27879199
TI  - An NMDA receptor-dependent mechanism for subcellular segregation of sensory
      inputs in the tadpole optic tectum.
AB  - In the vertebrate CNS, afferent sensory inputs are targeted to specific depths or
      layers of their target neuropil. This patterning exists ab initio, from the very
      beginning, and therefore has been considered an activity-independent process.
      However, here we report that, during circuit development, the subcellular
      segregation of the visual and mechanosensory inputs to specific regions of tectal
      neuron dendrites in the tadpole optic tectum requires NMDA receptor activity.
      Blocking NMDARs during the formation of these sensory circuits, or removing the
      visual set of inputs, leads to less defined segregation, and suggests a
      correlation-based mechanism in which correlated inputs wire to common regions of
      dendrites. This can account for how two sets of inputs form synapses onto
      different regions of the same dendrite. Blocking NMDA receptors during later
      stages of circuit development did not disrupt segregation, indicating a critical
      period for activity-dependent shaping of patterns of innervation.

PMID- 27879201
TI  - Visual attention is available at a task-relevant location rapidly after a
      saccade.
AB  - Maintaining attention at a task-relevant spatial location while making eye
      movements necessitates a rapid, saccade-synchronized shift of attentional
      modulation from the neuronal population representing the task-relevant location
      before the saccade to the one representing it after the saccade. Currently, the
      precise time at which spatial attention becomes fully allocated to the task
      relevant location after the saccade remains unclear. Using a fine-grained
      temporal analysis of human peri-saccadic detection performance in an attention
      task, we show that spatial attention is fully available at the task-relevant
      location within 30 milliseconds after the saccade. Subjects tracked the
      attentional target veridically throughout our task: i.e. they almost never
      responded to non-target stimuli. Spatial attention and saccadic processing
      therefore co-ordinate well to ensure that relevant locations are attentionally
      enhanced soon after the beginning of each eye fixation.

PMID- 27879200
TI  - Mechanism of cargo-directed Atg8 conjugation during selective autophagy.
AB  - Selective autophagy is mediated by cargo receptors that link the cargo to the
      isolation membrane via interactions with Atg8 proteins. Atg8 proteins are
      localized to the membrane in an ubiquitin-like conjugation reaction, but how this
      conjugation is coupled to the presence of the cargo is unclear. Here we show that
      the S. cerevisiae Atg19, Atg34 and the human p62, Optineurin and NDP52 cargo
      receptors interact with the E3-like enzyme Atg12~Atg5-Atg16, which stimulates
      Atg8 conjugation. The interaction of Atg19 with the Atg12~Atg5-Atg16 complex is
      mediated by its Atg8-interacting motifs (AIMs). We identify the AIM-binding sites
      in the Atg5 subunit and mutation of these sites impairs selective autophagy. In a
      reconstituted system the recruitment of the E3 to the prApe1 cargo is sufficient
      to drive accumulation of conjugated Atg8 at the cargo. The interaction of the
      Atg12~Atg5-Atg16 complex and Atg8 with Atg19 is mutually exclusive, which may
      confer directionality to the system.

PMID- 27879202
TI  - Quantifying beta-catenin subcellular dynamics and cyclin D1 mRNA transcription
      during Wnt signaling in single living cells.
AB  - Signal propagation from the cell membrane to a promoter can induce gene
      expression. To examine signal transmission through sub-cellular compartments and
      its effect on transcription levels in individual cells within a population, we
      used the Wnt/beta-catenin signaling pathway as a model system. Wnt signaling
      orchestrates a response through nuclear accumulation of beta-catenin in the cell
      population. However, quantitative live-cell measurements in individual cells
      showed variability in nuclear beta-catenin accumulation, which could occur in two
      waves, followed by slow clearance. Nuclear accumulation dynamics were initially
      rapid, cell cycle independent and differed substantially from LiCl stimulation,
      presumed to mimic Wnt signaling. beta-catenin levels increased simultaneously at
      adherens junctions and the centrosome, and a membrane-centrosome transport system
      was revealed. Correlating beta-catenin nuclear dynamics to cyclin D1
      transcriptional activation showed that the nuclear accumulation rate of change of
      the signaling factor, and not actual protein levels, correlated with the
      transcriptional output of the pathway.

PMID- 27879204
TI  - Establishment and maintenance of heritable chromatin structure during early
      Drosophila embryogenesis.
AB  - During embryogenesis, the initial chromatin state is established during a period
      of rapid proliferative activity. We have measured with 3-min time resolution how
      heritable patterns of chromatin structure are initially established and
      maintained during the midblastula transition (MBT). We find that regions of
      accessibility are established sequentially, where enhancers are opened in advance
      of promoters and insulators. These open states are stably maintained in highly
      condensed mitotic chromatin to ensure faithful inheritance of prior accessibility
      status across cell divisions. The temporal progression of establishment is
      controlled by the biological timers that control the onset of the MBT. In
      general, acquisition of promoter accessibility is controlled by the biological
      timer that measures the nucleo-cytoplasmic (N:C) ratio, whereas timing of
      enhancer accessibility is regulated independently of the N:C ratio. These
      different timing classes each associate with binding sites for two transcription
      factors, GAGA-factor and Zelda, previously implicated in controlling chromatin
      accessibility at ZGA.

PMID- 27879203
TI  - Fetal and neonatal hematopoietic progenitors are functionally and
      transcriptionally resistant to Flt3-ITD mutations.
AB  - The FLT3 Internal Tandem Duplication (FLT3ITD) mutation is common in adult acute
      myeloid leukemia (AML) but rare in early childhood AML. It is not clear why this
      difference occurs. Here we show that Flt3ITD and cooperating Flt3ITD/Runx1
      mutations cause hematopoietic stem cell depletion and myeloid progenitor
      expansion during adult but not fetal stages of murine development. In adult
      progenitors, FLT3ITD simultaneously induces self-renewal and myeloid commitment
      programs via STAT5-dependent and STAT5-independent mechanisms, respectively.
      While FLT3ITD can activate STAT5 signal transduction prior to birth, this
      signaling does not alter gene expression until hematopoietic progenitors
      transition from fetal to adult transcriptional states. Cooperative interactions
      between Flt3ITD and Runx1 mutations are also blunted in fetal/neonatal
      progenitors. Fetal/neonatal progenitors may therefore be protected from leukemic
      transformation because they are not competent to express FLT3ITD target genes.
      Changes in the transcriptional states of developing hematopoietic progenitors may
      generally shape the mutation spectra of human leukemias.

PMID- 27879207
TI  - Integration-free erythroblast-derived human induced pluripotent stem cells
      (iPSCs) from an individual with Ataxia-Telangiectasia (A-T).
AB  - Peripheral blood was obtained from a 12-year old male carrying bialleleic
      inactivating mutations at the ATM locus, causing Ataxia-Telangiectasia (A-T).
      Blood erythroid cells were briefly expanded in vitro and induced pluripotent stem
      cells (iPSCs) were generated via transfection with episomal vectors carrying
      hOCT4, hSOX2, hKLF4, hMYC and hBCL2L1. SF-003 iPSCs were free of genomically
      integrated reprogramming genes, had the specific compound heterozygous mutations,
      stable karyotype, expressed pluripotency markers and formed teratomas in
      immunodeficient (NOD scid gamma; NGS) mice. The SF-003 iPSC line may be a useful
      resource for in vitro modeling of A-T.

PMID- 27879205
TI  - Structure of protein O-mannose kinase reveals a unique active site architecture.
AB  - The 'pseudokinase' SgK196 is a protein O-mannose kinase (POMK) that catalyzes an
      essential phosphorylation step during biosynthesis of the laminin-binding glycan
      on alpha-dystroglycan. However, the catalytic mechanism underlying this activity
      remains elusive. Here we present the crystal structure of Danio rerio POMK in
      complex with Mg2+ ions, ADP, aluminum fluoride, and the GalNAc-beta3-GlcNAc-beta4
      Man trisaccharide substrate, thereby providing a snapshot of the catalytic
      transition state of this unusual kinase. The active site of POMK is established
      by residues located in non-canonical positions and is stabilized by a disulfide
      bridge. GalNAc-beta3-GlcNAc-beta4-Man is recognized by a surface groove, and the
      GalNAc-beta3-GlcNAc moiety mediates the majority of interactions with POMK.
      Expression of various POMK mutants in POMK knockout cells further validated the
      functional requirements of critical residues. Our results provide important
      insights into the ability of POMK to function specifically as a glycan kinase,
      and highlight the structural diversity of the human kinome.

PMID- 27879208
TI  - Generation of induced pluripotent stem cells (iPSCs) from a retinoblastoma
      patient carrying a c.2663G>A mutation in RB1 gene.
AB  - Skin fibroblasts were obtained from a male patient diagnosed with retinoblastoma
      (RB) carrying a c.2663G>A mutation in the 25 exon of RB1 gene. RB-iPS cells was
      generated via delivered four reprogramming factors (OCT4, SOX2, NANOG and LIN28)
      into these skin fibroblasts. The RB-iPS cells retained the RB1 heterozygous
      mutation resulted in a truncated RB1 mRNA. Characteristic tests proved that the
      iPSC line presented typical markers of pluripotency and had the capability to
      form the three germ layers in vitro.

PMID- 27879206
TI  - Exon junction complex proteins bind nascent transcripts independently of pre-mRNA
      splicing in Drosophila melanogaster.
AB  - Although it is currently understood that the exon junction complex (EJC) is
      recruited on spliced mRNA by a specific interaction between its central protein,
      eIF4AIII, and splicing factor CWC22, we found that eIF4AIII and the other EJC
      core proteins Y14 and MAGO bind the nascent transcripts of not only intron
      containing but also intronless genes on Drosophila polytene chromosomes.
      Additionally, Y14 ChIP-seq demonstrates that association with transcribed genes
      is also splicing-independent in Drosophila S2 cells. The association of the EJC
      proteins with nascent transcripts does not require CWC22 and that of Y14 and MAGO
      is independent of eIF4AIII. We also show that eIF4AIII associates with both
      polysomal and monosomal RNA in S2 cell extracts, whereas Y14 and MAGO fractionate
      separately. Cumulatively, our data indicate a global role of eIF4AIII in gene
      expression, which would be independent of Y14 and MAGO, splicing, and of the EJC,
      as currently understood.

PMID- 27879209
TI  - Generation of an induced pluripotent stem cell line from a patient with chronic
      myeloid leukemia (CML) resistant to targeted therapies.
AB  - Chronic myeloid leukemia (CML) is a clonal malignancy initiated by the occurrence
      of a t (9;22) translocation, generating Ph1 chromosome and BCR-ABL oncogene in a
      primitive hematopoietic stem cell (HSC). The resistance of HSC to targeted
      therapies using tyrosine kinase inhibitors remains a major obstacle towards the
      cure. We have generated an iPSC line from a patient with CML using leukemic CD34+
      cells cryopreserved at diagnosis. Ph1+ CML cells were reprogrammed by non
      integrative viral transduction. These iPSCs harboured Ph1 chromosome and
      expressed pluripotency hallmarks as well as BCR-ABL. Teratoma assays revealed
      normal differentiation after injection in immunodeficient mice.

PMID- 27879210
TI  - Murine transgenic iPS cell line for monitoring and selection of cardiomyocytes.
AB  - We report here a transgenic murine induced pluripotent stem cell (iPSC) line
      expressing puromycin N-acetyltransferase (PAC) and enhanced green fluorescent
      protein (EGFP) under the control of alpha-myosin heavy chain promoter. This
      transgenic cell line reproducibly differentiates into EGFP-expressing
      cardiomyocytes (CMs) which can be generated at high purity with puromycin
      treatment and exhibit molecular and functional properties of immature heart
      muscle cells. This genetically modified iPSC line can be used for assessment of
      the utility of CMs for myocardial repair, pharmacological and toxicological
      applications and development of improved cardiac differentiation protocols.

PMID- 27879211
TI  - Generation of a human induced pluripotent stem cell (iPSC) line from a patient
      carrying a P33T mutation in the PDX1 gene.
AB  - Homozygous loss-of-function mutations in the gene coding for the homeobox
      transcription factor PDX1 leads to pancreatic agenesis, whereas certain
      heterozygous point mutations are associated with Maturity-Onset Diabetes of the
      Young 4 (MODY4) and Type 2 Diabetes Mellitus (T2DM). To understand the
      pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a
      P33T heterozygous mutation in the transactivation domain of PDX1. The resulting
      PDX1 P33T iPSCs generated by episomal reprogramming are integration-free, have a
      normal karyotype and are pluripotent in vitro and in vivo. Taken together, this
      iPSC line will be useful to study diabetes pathomechanisms.

PMID- 27879212
TI  - Generation of a gene-corrected isogenic control cell line from an Alzheimer's
      disease patient iPSC line carrying a A79V mutation in PSEN1.
AB  - Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative
      disease causing neural cell degeneration and brain atrophy and is considered to
      be the most common form of dementia. We previously generated an induced
      pluripotent stem cell (iPSC) line from an AD patient carrying an A79V mutation in
      PSEN1 as an in vitro disease model. Here we generated a gene-corrected version
      from this hiPSC line by substituting the point mutation with the wild-type
      sequence. The reported A79V-GC-iPSCs line is a very useful resource in
      combination with the A79V-iPSC line in order to study pathological cellular
      phenotypes related to this particular mutation.

PMID- 27879213
TI  - Generation of HEXA-deficient hiPSCs from fibroblasts of a Tay-Sachs disease
      patient.
AB  - Human iPSC line TSD-01-hiPSC was generated from fibroblasts of a patient with
      infantile Tay-Sachs disease (TSD). The patient is compound heterozygous at the
      HEXA gene by carrying a 1278insTATC allele and an IVS12+1G>C allele. STEMCCA
      lentivirus, which expresses OCT4, SOX2, KLF4, and c-MYC from a polycistronic
      transcript, were used for reprogramming. TSD-01-hiPSC express pluripotency
      markers such as OCT4, SOX2, NANOG, Tra-1-60, and alkaline phosphatase, and can
      differentiate into tissues from all the three embryonic germ layers. This TSD
      patient-derived hiPSC line may serve as a valuable in vitro tool for disease
      modeling and drug test.

PMID- 27879214
TI  - Generation of a human induced pluripotent stem cell (iPSC) line from a patient
      with family history of diabetes carrying a C18R mutation in the PDX1 gene.
AB  - Homozygous loss-of-function mutations in the gene coding for the homeobox
      transcription factor PDX1 leads to pancreatic agenesis, whereas certain
      heterozygous point mutations are associated with Maturity-Onset Diabetes of the
      Young 4 (MODY4) and Type 2 Diabetes Mellitus (T2DM). To understand the
      pathomechanism of MODY4 and T2DM, we have generated iPSCs from a woman with a
      C18R heterozygous mutation in the transactivation domain of PDX1. The resulting
      PDX1 C18R iPSCs generated by episomal reprogramming are integration-free, have a
      normal karyotype and are pluripotent in vitro and in vivo. Taken together, this
      iPSC line will be useful to study diabetes pathomechanisms.

PMID- 27879215
TI  - A human VE-cadherin-tdTomato and CD43-green fluorescent protein dual reporter
      cell line for study endothelial to hematopoietic transition.
AB  - Human embryonic stem cell line WA01 was genetically modified using zinc-finger
      nucleases and the PiggyBac/transponson system to introduce a fluorescence
      reporter for VE-cadherin (VEC; tdTomato) and CD43 (eGFP). Phenotypic and
      functional assays for pluripotency revealed the modified hES cell reporter lines
      remained normal. When the cells were differentiated into hematoendothelial
      lineages, either by directed differentiation or direct reprogramming, flow
      cytometric and fluorescence microscopy showed that VEC+ endothelial cells express
      tdTomato and CD43+ hematopoietic progenitors express eGFP.

PMID- 27879216
TI  - Generation of induced pluripotent stem cells (iPSCs) from a hereditary spastic
      paraplegia patient carrying a homozygous R486C mutation in CYP7B1 (SPG5).
AB  - Skin fibroblasts were obtained from a 47-year-old hereditary spastic paraplegia
      patient carrying a homozygous mutation R486C in CYP7B1 (Cytochrome P450, Family
      7, Subfamily B, Polypeptide 1), responsible for causing hereditary spastic
      paraplegia type 5 (SPG5). Induced pluripotent stem cells (iPSCs) were generated
      by transfection with episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and
      hLIN28. The generated line iPS-SPG5-R486C was transgene-free, retained the
      specific mutation with no additional genomic aberrations, expressed pluripotency
      markers and was able to differentiate into cells of all germ layers in vitro. The
      generated iPS-SPG5-R486C line may be a useful resource for disease modelling of
      SPG5.

PMID- 27879217
TI  - Generation of optic atrophy 1 patient-derived induced pluripotent stem cells (iPS
      OPA1-BEHR) for disease modeling of complex optic atrophy syndromes (Behr
      syndrome).
AB  - Human skin fibroblasts were isolated from a 48-year-old patient carrying compound
      heterozygous mutations (c.610+364G>A and c.1311A>G) in OPA1, responsible for
      early onset optic atrophy complicated by ataxia and pyramidal signs (Behr
      syndrome; OMIM #210000). Fibroblasts were reprogrammed using episomal plasmids
      carrying hOCT4, hSOX2, hKLF4, hL-MYC and hLIN28. The generated transgene-free
      line iPS-OPA1-BEHR showed no additional genomic aberrations, maintained the
      disease-relevant mutations, expressed important pluripotency markers and was
      capable to differentiate into cells of all three germ layers in vitro. The
      generated iPS-OPA1-BEHR line might be a useful platform to study the
      pathomechanism of early onset complicated optic atrophy syndromes.

PMID- 27879218
TI  - Generation of a TLE1 homozygous knockout human embryonic stem cell line using
      CRISPR-Cas9.
AB  - Here, we generated a biallelic mutation in the TLE1 (Transducin Like Enhancer of
      Split 1) gene using CRISPR-Cas9 editing in the human embryonic stem cell (hESC)
      line WA01. The homozygous knockout cell line, TLE1-464-G04, displays loss of TLE1
      protein expression while maintaining pluripotency, differentiation potential and
      genomic integrity.

PMID- 27879219
TI  - Induced pluripotent stem cells (iPSCs) derived from cerebrotendinous
      xanthomatosis (CTX) patient's fibroblasts carrying a R395S mutation.
AB  - Induced pluripotent stem cells (iPSCs) were generated from dermal fibroblasts
      from a 60-year-old cerebrotendinous xanthomatosis (CTX) patient, carrying a
      homozygous mutation c. [1183C>A]; p. R395S in CYP27A1. Episomal plasmids encoding
      the pluripotency genes OCT4, SOX2, KLF4, L-MYC and LIN28 were introduced via
      electroporation. The generated line iPS-CTX-R395S has no sign of plasmid
      integration or chromosomal aberration and retained the mutation site in CYP27A1.
      Furthermore, iPSCs express pluripotency markers and are able to differentiate in
      all germ layers in vitro. The generated line may be a useful tool for disease
      modelling of CTX.

PMID- 27879220
TI  - Generation of induced pluripotent stem cells (iPSCs) from a hereditary spastic
      paraplegia patient carrying a homozygous Y275X mutation in CYP7B1 (SPG5).
AB  - Skin fibroblasts were obtained from a 47-year-old hereditary spastic paraplegia
      patient carrying a homozygous mutation Y275X in CYP7B1 (Cytochrome P450, Family
      7, Subfamily B, Polypeptide 1), responsible for causing hereditary spastic
      paraplegia type 5 (SPG5). Induced pluripotent stem cells (iPSCs) were generated
      by transfection with episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC and
      hLIN28. The generated line iPS-SPG5-Y275X was transgene-free, retained the
      specific mutation with no additional genomic aberrations, expressed pluripotency
      markers and was able to differentiate into cells of all germ layers in vitro. The
      generated iPS-SPG5-Y275X line may be a useful resource for disease modelling of
      SPG5.

PMID- 27879221
TI  - Generation of a TLE3 heterozygous knockout human embryonic stem cell line using
      CRISPR-Cas9.
AB  - Here, we generated a monoallelic mutation in the TLE3 (Transducin Like Enhancer
      of Split 3) gene using CRISPR-Cas9 editing in the human embryonic stem cell
      (hESC) line WA01. The heterozygous knockout cell line, TLE3-447-D08-A01, displays
      partial loss of TLE3 protein expression while maintaining pluripotency,
      differentiation potential and genomic integrity.

PMID- 27879222
TI  - An integration-free, virus-free rhesus macaque induced pluripotent stem cell line
      (riPSC89) from embryonic fibroblasts.
AB  - We generated a rhesus macaque induced pluripotent stem cell (riPSC) line,
      riPSC89, from rhesus embryonic fibroblasts (REFs). Fibroblasts were expanded from
      the skin of a rhesus macaque embryo at embryonic day 47. REFs and riPSCs had a
      normal male (42, XY) karyotype. The riPSC89 line was positive for markers of self
      renewal including OCT4, NANOG, TRA-1-81 and SSEA4. Pluripotency was demonstrated
      through the generation of teratomas using transplantation into immunocompromised
      mice. The riPSC89 line may be a useful non-human primate resource to uncover
      developmental origins of disease, or used as a basic model to understand lineage
      specification in the primate embryo.

PMID- 27879223
TI  - Generation of human induced pluripotent stem cells in defined, feeder-free
      conditions.
AB  - Herein, we describe a modified protocol for the generation of human induced
      pluripotent stem cells (hiPS) and expansion under defined, serum free and feeder
      free conditions. These cells exhibit a high level of plasticity towards various
      differentiation pathways both in vitro and in vivo. Ultimately, hiPS-derived
      lines achieved high standards of three dimensional differentiations on
      biomaterial scaffolds and promoted in vivo regeneration of complex organs, such
      as Anterior Cruciate Ligament (in swine ACL-rupture models) and other tissues as
      well.

PMID- 27879224
TI  - A Comparison of Cartilage Palisades and Temporal Fascia in Type 1 Tympanoplasty
      for Bilateral Tympanic Membrane Perforations in Children.
AB  - OBJECTIVE: To compare the graft success rates and audiological outcomes of
      bilaterally performed type 1 tympanoplasty using cartilage palisades or temporal
      fascia in children. MATERIALS AND METHODS: We retrospectively analyzed the
      medical records of patients who underwent type 1 tympanoplasty at Medical Park
      Hospital between May 2007 and February 2013. 27 patients (54 ears) were enrolled
      in the study: 15 (30 ears) in the palisade cartilage group and 12 (24 ears) in
      the fascia group. RESULTS: The graft success rate for the fascia group was 79.2%,
      and that for the cartilage group was 96.7%. The difference was statistically
      insignificant (p=0.078). Audiological improvements were seen in both groups, and
      the difference was statistically insignificant. CONCLUSION: The use of temporalis
      fascia grafting has similar outcomes to palisade cartilage tympanoplasty for both
      success rate and audiological values in children who have bilateral disease.

PMID- 27879225
TI  - Efficacy of Posterior Canal Wall Reconstruction Using Autologous Auricular
      Cartilage and Bone Pate in Chronic Otitis Media with Cholesteatoma.
AB  - OBJECTIVE: This study was designed to investigate the long-term results using the
      technique of canal wall up mastoidectomy and reconstruction of the posterior
      canal wall using bone pate and auricular cartilage in the treatment of chronic
      otitis media with cholesteatoma. MATERIALS AND METHODS: A retrospective review
      was performed on 42 patients who underwent canal wall up mastoidectomy and
      posterior canal wall reconstruction at a single institution between November 2005
      and November 2012. RESULTS: Of the 42 patients, postoperative tympanic membranes
      were normal in 38 (90.5%), perforated in 1 (2.4%), and retracted in 3 (7.1%).
      Mean preoperative and postoperative values of the air-bone gap (ABG) were 29.4+/
      12.8 and 23.4+/-11.7 dB, respectively, which represented a significant average
      improvement. For patients with ossiculoplasty (n=24), the mean preoperative and
      postoperative ABG values were 34.7+/-6.0 and 27.5+/-8.0 dB, respectively, which
      also represented a significant average improvement. Thirty-one (73.8%) of the
      patients were followed up without any complication, but 5 had otorrhea (11.9%), 4
      had dizziness (9.5%), and 2 had facial palsy (4.8%). CONCLUSION: A canal wall up
      mastoidectomy with reconstruction of the posterior canal wall using auricular
      cartilage and bone pate provides successful preservation of the anatomic
      structure and a significant improvement in hearing without the long-term
      disadvantages of a canal wall down mastoidectomy.

PMID- 27879227
TI  - Correlation between cVEMP and ABR for the Evaluation of Vestibular Migraine.
AB  - OBJECTIVE: Vestibular migraine (VM) is a clinical condition characterized by
      temporal overlap between vestibular symptoms and migraine. In this study, we
      aimed to determine the changes in vestibular myogenic potential (cVEMP) and
      auditory brainstem response (ABR) in patients with VM and migraine. MATERIALS AND
      METHODS: A total of 86 participants with no hearing loss or additional disease
      between the ages of 18 and 45 were enrolled in three different groups: group 1,
      VM; group 2, migraine without aura; and group 3, healthy controls. cVEMP and ABR
      were performed for all participants during attacks and attack-free periods. The
      differences between the right and left sides were calculated. RESULTS: There was
      no significant difference in cVEMP p13-n23 latencies between any of the groups.
      There were statistically significant differences related to cVEMP p13-n23
      amplitudes between groups 1, 2, and 3. This significant difference originated
      from group 1 when compared with the other groups (p<0.05). When we compared the
      cVEMP results of patients with VM during attack and attack-free periods, a
      statistically significant decrease was determined in the p13-n23 amplitude values
      during the attack period (p<0.01). Additionally, when we compared group 1 and
      group 3, the wave V peak latencies in ABR were significantly prolonged in group 1
      (p<0.05). CONCLUSION: cVEMP and ABR can be used as diagnostic criteria for
      patients with VM during attacks. Further studies with larger groups are needed to
      verify our findings.

PMID- 27879226
TI  - Speech-Evoked Auditory Brainstem Response in Individuals with Diabetes Mellitus
      Type 2.
AB  - OBJECTIVE: Diabetes is the most common glucose level dependent metabolic disorder
      and studies have shown that hearing impairment can be a long-term subclinical
      complication. Studies to investigate auditory system involvement in diabetes has
      focused majorly on the auditory brainstem response (ABR), otoacoustic emission,
      and basic audiological measures. Hence in the current study, we used speech
      evoked ABR (S-ABR) as a tool to see the effect of diabetes on both a transient
      and sustained response of the auditory brainstem to a conventionally used
      consonant-vowel (CV) stimuli /da/. MATERIALS AND METHODS: This preliminary
      investigation was done on 22 individuals in the age range of 40-55 years. 11
      individuals were diabetics for a minimum period of five years. The S-ABR was
      recorded for all the participants with speech stimuli /da/ of 40 ms duration.
      Latency analysis of the waves V, A, D, E, F, and O were carried out. The
      statistical analysis included descriptive measures, paired t tests, and MANOVA.
      RESULTS: The findings of the current study suggest that middle-aged individuals
      with diabetes have a significant deficiency in auditory processing at the
      brainstem level. Both transient (wave V (p=0.00), A (p=0.00), and O (p=0.00)) and
      sustained responses (wave D (p=0.001), E (p=0.00), and F (p=0.00)) of the S-ABR
      were found to be affected in diabetic individuals compared to age-matched non
      diabetic individuals. CONCLUSION: Considering diabetes is a common metabolic
      disorder in the middle-aged Indian population, the findings of the present study
      can have significant clinical implication.

PMID- 27879228
TI  - Identifying the Optimal Water-Occluding Earplugs: A Scientific Simulation Study.
AB  - OBJECTIVE: Numerous types of water-occluding earplugs are available as a means of
      preventing infection in patients with external and middle ear disease. However,
      little is known about the comparative efficacies of these earplugs with prolonged
      water exposure. In this study, we assessed the water impermeability of various
      earplug materials to prolonged water exposure. MATERIALS AND METHODS: Nine
      earplugs were tested: cotton wool mixed with petroleum jelly, cotton wool
      externally coated with petroleum jelly, Blu-Tack, foam earplugs, silicone putty,
      silicone earplugs, flanged earplugs, and hard and soft silicone custom-moulds.
      Precision-engineered cups were filled with 30 mL water and sealed with lids that
      contained a 10 mm diameter hole to simulate the ear canal. The aperture was
      occluded with different earplugs, and the cup was inverted. Computer software was
      used to record the water loss to the nearest 10 milligrams 720 times over a three
      hour period. The test was repeated five times for each material. RESULTS: The
      water permeability onset, rate, and total amount of water loss varied markedly
      between the materials; cotton wool mixed with petroleum jelly demonstrated the
      fastest onset of leak and the highest rate of water loss (p < 0.00001), as well
      as the largest amount of cumulative water loss (p = 0.00213). The soft silicone
      custom-mould plugs, hard silicone custom-mould plugs, foam plugs, and silicone
      putty demonstrated no leaks. CONCLUSION: This study demonstrates a wide range of
      water permeabilities of commonly used ear-occluding materials during prolonged
      water exposure. We found that the generally suggested regimen of cotton wool
      mixed with petroleum jelly may be inefficacious for substantial periods of water
      exposure.

PMID- 27879229
TI  - The Incidence of Ototoxicity in Patients Using Iron Chelators.
AB  - OBJECTIVE: In this study, we aimed to detect the incidences of ototoxicity in
      patients with hemoglobinopathies taking deferoxamine (DFO), deferiprone, and
      deferasirox using the National Cancer Institute (NCI) Common Terminology Criteria
      for Adverse Events (CTCAE) scale to obtain more objective data. MATERIALS AND
      METHODS: Fifty-five transfusion-dependent patients were evaluated in this study.
      The NCI CTCAE scale was used to assess ototoxicity levels. The average ferritin
      and hemoglobin levels, the type of iron chelator, and the duration of therapy of
      all the patients were recorded. RESULTS: Ototoxicity was observed in 15 patients
      (31.9 %), all of whom were taking DFO. The median age was 19.5 (6-43) in patients
      without ototoxicity and 29 (16-50) in those with ototoxicity; this difference was
      statistically significant (p<0.05). The median ferritin and pre-tx Hb levels were
      1391 ng/mL and 9.06 mg/dL, respectively, in patients with ototoxicity and 986.7
      ng/mL and 9.24 mg/dL, respectively, in those without ototoxicity; these
      differences were not significant (p>0.05). Ototoxicity was not observed in the
      eight patients who used only deferasirox and deferiprone. CONCLUSION: The
      ototoxicity incidence with DFO at doses below 50 mg/kg/day was 27.3%. Deferiprone
      and deferasirox were not associated with ototoxic effects in patients taking
      these drugs.

PMID- 27879231
TI  - Corrigenda for vol. 265, p. E210.

PMID- 27879230
TI  - Bilateral Cochleovestibulopathy Due to Internal Auditory Canal Metastasis in a
      Patient with Stomach Cancer.
AB  - Bilateral sudden onset hearing loss and vestibular dysfunction due to metastatic
      carcinoma of the internal auditory canal (IAC) on both sides is an extremely rare
      occurrence. This is a challenging case in neuro-otology that is difficult to
      relieve by medical support, and spontaneous compensation by vestibular
      rehabilitation is minimal. The spread of tumor cells to the cerebrospinal space
      indicates poor prognosis. We present a patient with stage-III gastric carcinoma
      who experienced sudden hearing loss and severe imbalance. Radiological
      investigation revealed bilateral metastasis of the IAC. Clinical aspects,
      diagnosis, and treatment issues related to bilateral cochleovestibulopathy are
      discussed.

PMID- 27879232
TI  - ASHP Foundation Pharmacy Forecast 2017: Strategic Planning Advice for Pharmacy
      Departments in Hospitals and Health Systems.

PMID- 27879233
TI  - ASHP Research and Education Foundation's Pharmacy Forecast: An essential resource
      for pharmacy practice.

PMID- 27879234
TI  - Corrigenda for vol. 266, p. E560.

PMID- 27879235
TI  - Corrigenda for vol. 270, p. E413.

PMID- 27879236
TI  - Corrigenda for vol. 270, p. E413.

PMID- 27879237
TI  - Corrigenda for vol. 266, p. E17.

PMID- 27879238
TI  - Government must not shy away from bold action on public health, says MP.

PMID- 27879240
TI  - Adrenal suppression with glucocorticoid therapy: still a problem after all these
      years?

PMID- 27879241
TI  - Sixty seconds on . . . cryopreservation.

PMID- 27879242
TI  - What next for refugees after demolition of the Calais camp?

PMID- 27879243
TI  - Digital hub cuts care home referrals to GPs by more than a third.

PMID- 27879244
TI  - Ailing NHS finances are not sustainable, government auditors warn.

PMID- 27879245
TI  - Sam Everington: the proud generalist.

PMID- 27879247
TI  - General practices must appoint whistleblowing guardian.

PMID- 27879246
TI  - Father involvement in early child-rearing and behavioural outcomes in their pre
      adolescent children: evidence from the ALSPAC UK birth cohort.
AB  - OBJECTIVE: To explore the nature of paternal involvement in early child-rearing
      adopting a social developmental perspective, and estimate its effect on
      behavioural outcomes of children aged 9 and 11 years. SETTING: The data come from
      the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort recruited in
      the former county of Avon in the southwest of England. PARTICIPANTS: Out of the
      14 701 children in this cohort who were alive at 1 year, 10 440 children were
      living with both parents at 8 months and were therefore eligible. Outcome data
      were available for 6898 children at 9 years and 6328 children at 11 years. MAIN
      EXPOSURE: Paternal involvement was measured using factor scores obtained through
      factor analysis of fathers' responses on their participation in, understanding
      of, and feelings about their child's early upbringing. OUTCOME: Behavioural
      problems were measured using the Strengths and Difficulties Questionnaire (SDQ)
      total difficulties score. RESULTS: 3 factors were identified in the factor
      analysis: Factor 1 described fathers' emotional response to the child; factor 2
      measured the frequency of fathers' involvement in domestic and childcare
      activities; factor 3 characterised fathers' feelings of security in their role as
      parent and partner. Children of fathers with high scores on factors 1 and 3 had
      14% (OR 0.86, 95% CI 0.79 to 0.94, p=0.001) and 13% (OR 0.87, 95% CI 0.79 to
      0.96, p=0.006), respectively, lower adjusted odds of behavioural problems at 9
      years. Factors 1 and 3 were associated with comparable reduction in adjusted odds
      of behavioural problems at 11 years (OR 0.89, 95% CI 0.81 to 0.98, p=0.017 and OR
      0.89, 95% CI 0.81 to 0.99, p=0.034, respectively). Factor 2 was not associated
      with the outcome. CONCLUSIONS: Psychological and emotional aspects of paternal
      involvement in children's early upbringing, particularly how new fathers see
      themselves as parents and adjust to the role, rather than the quantity of direct
      involvement in childcare, is associated with positive behavioural outcomes in
      children.

PMID- 27879249
TI  - Glucosamine induces ER stress by disrupting lipid-linked oligosaccharide
      biosynthesis and N-linked protein glycosylation.
AB  - Glucosamine is an essential substrate for N-linked protein glycosylation.
      However, elevated levels of glucosamine can induce endoplasmic reticulum (ER)
      stress. Glucosamine-induced ER stress has been implicated in the development of
      diabetic complications, including atherosclerosis and hepatic steatosis. In this
      study, we investigate the potential relationship between the effects of
      glucosamine on lipid-linked oligosaccharide (LLO) biosynthesis, N-linked
      glycosylation, and ER homeostasis. Mouse embryonic fibroblasts (MEFs) were
      cultured in the presence of 0-5 mM glucosamine for up to 18 h, and LLO
      biosynthesis was monitored by fluorescence-assisted carbohydrate electrophoresis.
      ER stress was determined by quantification of unfolded protein response (UPR)
      gene expression. We found that exposure of MEFs to >=1 mM glucosamine
      significantly impaired the biosynthesis of mature (Glc3Man9GlcNAc2) LLOs before
      the activation of the UPR, which resulted in the accumulation of an LLO
      intermediate (Man3GlcNAc2). The addition of 4-phenylbutyric acid (4-PBA), a
      chemical chaperone, was able to alleviate ER stress but did not rescue LLO
      biosynthesis. Other ER stress-inducing agents, including dithiothreitol and
      thapsigargin, had no effect on LLO levels. Together, these data suggest that
      elevated concentrations of glucosamine induce ER stress by interfering with lipid
      linked oligosaccharide biosynthesis and N-linked glycosylation. We hypothesize
      that this pathway represents a causative link between hyperglycemia and the
      development of diabetic complications.

PMID- 27879248
TI  - High-fat diet-induced obesity regulates MMP3 to modulate depot- and sex-dependent
      adipose expansion in C57BL/6J mice.
AB  - Increased adipocyte size is hypothesized to signal the recruitment of adipose
      progenitor cells (APCs) to expand tissue storage capacity. To investigate depot
      and sex differences in adipose growth, male and female C57BL/6J mice (10 wk-old)
      were challenged with high-fat (HF) or low-fat (LF) diets (D) for 14 wk. The HFD
      increased gonadal (GON) depot weight by adipocyte hypertrophy and hyperplasia in
      females but hypertrophy alone in males. In both sexes, inguinal (ING) adipocytes
      were smaller than GON, and depot expansion was due to hypertrophy. Matrix
      metalloproteinase 3 (Mmp3), an antiadipogenic factor, and its inhibitor Timps
      modulate the extracellular matrix remodeling needed for depot expansion. Mmp3
      mRNA was depot different (ING > GON), higher in females than males and mainly
      expressed in APCs. In males, HFD-induced obesity increased tissue and APC Mmp3
      mRNA levels and MMP3 protein and enzymatic activity. In females however, HFD
      significantly decreased MMP3 protein without affecting its mRNA levels. MMP3
      activity also decreased (significant in ING). Timp4 mRNA was expressed mainly in
      adipocytes, and HFD-induced obesity tended to increase the ratio of TIMP4 to MMP3
      protein in females, whereas it decreased it in males. Overexpression of Mmp3 in
      3T3-L1 preadipocytes or rhMMP3 protein added to primary human preadipocytes
      inhibited differentiation, whereas rhTIMP4 improved adipogenesis and attenuated
      the inhibitory effect of rhMMP3. These data suggest that HFD-induced obesity
      downregulates APC MMP3 expression to trigger adipogenesis, and adipocyte TIMP4
      may modulate this process to regulate hyperplastic vs. hypertrophic adipose
      tissue expansion, fat distribution, and metabolic health in a sex- and depot
      dependent manner.

PMID- 27879252
TI  - High-Density Lipoprotein-Associated Apolipoprotein M Limits Endothelial
      Inflammation by Delivering Sphingosine-1-Phosphate to the Sphingosine-1-Phosphate
      Receptor 1.
AB  - OBJECTIVE: Plasma high-density lipoproteins (HDL) are potent antiatherogenic and
      anti-inflammatory particles. However, HDL particles are highly heterogenic in
      composition, and different HDL-mediated functions can be ascribed to different
      subclasses of HDL. Only a small HDL population contains apolipoprotein M (ApoM),
      which is the main plasma carrier of the bioactive lipid mediator sphingosine-1
      phosphate (S1P). Vascular inflammation is modulated by S1P, but both pro- and
      anti-inflammatory roles have been ascribed to S1P. The goal of this study is to
      elucidate the role of ApoM and S1P in endothelial anti-inflammatory events
      related to HDL. APPROACH AND RESULTS: Aortic or brain human primary endothelial
      cells were challenged with tumor necrosis factor-alpha (TNF-alpha) as
      inflammatory stimuli. The presence of recombinant ApoM-bound S1P or ApoM
      containing HDL reduced the abundance of adhesion molecules in the cell surface,
      whereas ApoM and ApoM-lacking HDL did not. Specifically, ApoM-bound S1P decreased
      vascular adhesion molecule-1 (VCAM-1) and E-selectin surface abundance but not
      intercellular adhesion molecule-1. Albumin, which is an alternative S1P carrier,
      was less efficient in inhibiting VCAM-1 than ApoM-bound S1P. The activation of
      the S1P receptor 1 was sufficient and required to promote anti-inflammation.
      Moreover, ApoM-bound S1P induced the rearrangement of the expression of S1P
      related genes to counteract TNF-alpha. Functionally, HDL/ApoM/S1P limited
      monocyte adhesion to the endothelium and maintained endothelial barrier integrity
      under inflammatory conditions. CONCLUSIONS: ApoM-bound S1P is a key component of
      HDL and is responsible for several HDL-associated protective functions in the
      endothelium, including regulation of adhesion molecule abundance, leukocyte
      endothelial adhesion, and endothelial barrier.

PMID- 27879254
TI  - Henry J M Barnett.

PMID- 27879251
TI  - Altered Smooth Muscle Cell Force Generation as a Driver of Thoracic Aortic
      Aneurysms and Dissections.
AB  - The importance of maintaining contractile function in aortic smooth muscle cells
      (SMCs) is evident by the fact that heterozygous mutations in the major structural
      proteins or kinases controlling contraction lead to the formation of aneurysms of
      the ascending thoracic aorta that predispose to life-threatening aortic
      dissections. Force generation by SMC requires ATP-dependent cyclic interactions
      between filaments composed of SMC-specific isoforms of alpha-actin (encoded by
      ACTA2) and myosin heavy chain (MYH11). ACTA2 and MYH11 mutations are predicted or
      have been shown to disrupt this cyclic interaction predispose to thoracic aortic
      disease. Movement of the myosin motor domain is controlled by phosphorylation of
      the regulatory light chain on the myosin filament, and loss-of-function mutations
      in the dedicated kinase for this phosphorylation, myosin light chain kinase
      (MYLK) also predispose to thoracic aortic disease. Finally, a mutation in the
      cGMP-activated protein kinase (PRKG1) results in constitutive activation of the
      kinase in the absence of cGMP, thus driving SMC relaxation in part through
      increased dephosphorylation of the regulatory light chain and predisposes to
      thoracic aortic disease. Furthermore, SMCs cannot generate force without
      connections to the extracellular matrix through focal adhesions, and mutations in
      the major protein in the extracellular matrix, fibrillin-1, linking SMCs to the
      matrix also cause thoracic aortic disease in individuals with Marfan syndrome.
      Thus, disruption of the ability of the aortic SMC to generate force through the
      elastin-contractile units in response to pulsatile blood flow may be a primary
      driver for thoracic aortic aneurysms and dissections.

PMID- 27879255
TI  - US must address addiction as an illness, not as a moral failing, Surgeon General
      says.

PMID- 27879253
TI  - The Yin-Yang Dynamics of DNA Methylation Is the Key Regulator for Smooth Muscle
      Cell Phenotype Switch and Vascular Remodeling.
AB  - OBJECTIVE: DNA methylation plays an important role in chronic diseases such as
      atherosclerosis, yet the mechanisms are poorly understood. The objective of our
      study is to indicate the regulatory mechanisms of DNA methylation in vascular
      smooth muscle cells (VSMCs) and its roles in atherosclerosis. APPROACH AND
      RESULTS: In ApoE-/- mice fed a Western diet, DNA methyltransferase inhibitor, 5
      aza-2'-deoxycytidine, significantly attenuated atherosclerotic lesions (20.1+/
      2.2% versus 30.8+/-7.5%; P=0.016) and suppressed DNA methyltransferase activity
      and concomitantly decreased global 5-methylcytosine content in atherosclerotic
      lesions of ApoE-/- mice. Using a carotid ligation model, we found that 5-aza-2'
      deoxycytidine also dramatically inhibited neointimal formation (intimal area:
      2.25+/-0.14*104 versus 4.07+/-0.22*104 MUm2; P<0.01). Abnormal methylation status
      at the promoter of ten-eleven translocation 2, one of the key demethylation
      enzymes in mammals, was ameliorated after 5-aza-2'-deoxycytidine treatment, which
      in turn caused an increase in global DNA hydroxymethylation and 5
      hydroxymethylcytosine enrichment at the promoter of Myocardin. In vitro, 5-aza-2'
      deoxycytidine treatment or DNA methyltransferase 1 knockdown decreased global 5
      methylcytosine content and restored Myocardin expression in VSMCs induced by
      platelet-derived growth factor, thus preventing excessive VSMCs
      dedifferentiation, proliferation, and migration. Furthermore, DNA
      methyltransferase 1 binds to ten-eleven translocation 2 promoter and is required
      for ten-eleven translocation 2 methylation in VSMCs. CONCLUSIONS: The inhibitory
      effects of DNA demethylation on global 5-methylcytosine content and ten-eleven
      translocation 2 hypermethylation in atherosclerotic aorta can recover 5
      hydroxymethylcytosine enrichment at the Myocardin promoter and prevent VSMC
      dedifferentiation and vascular remodeling.

PMID- 27879256
TI  - Determination and regulation of body composition in elite athletes.
AB  - In 2011, the International Association of Athletics Federations (IAAF) and IOC
      introduced a 'hyperandrogenism' rule that excluded women with a serum
      testosterone >10 nmol/L from participating in elite sport. This rule was based on
      the false premise that the greater lean body mass in men was a consequence of
      their higher serum testosterone. This rule did not have scientific backing and
      the Court of Arbitration for Sport subsequently rescinded the rule following an
      appeal from an Indian athlete barred from the Commonwealth Games. This review
      covers the scientific knowledge about the development and regulation of body
      composition in humans but also considers the lessons learnt from evolution and
      breeding in animals. The importance of heredity has been documented in family and
      twin studies. The roles of growth hormone and sex steroids are reviewed. The
      Androgen Insensitivity Syndrome (AIS) is considered as a model of the role of
      testosterone in development of body composition and also as evidence of the
      importance of other factors carried on the Y-chromosome that are of prime
      importance but have been systematically ignored. Finally the key factors
      determining body composition are considered and placed in a suggested order of
      importance.

PMID- 27879257
TI  - A phase 2 study of rituximab plus lenalidomide for mucosa-associated lymphoid
      tissue lymphoma.

PMID- 27879258
TI  - Nucleophosmin-anaplastic lymphoma kinase: the ultimate oncogene and therapeutic
      target.
AB  - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically
      expressed by fetal neural cells. However, aberrantly expressed ALK is involved in
      the pathogenesis of diverse malignancies, including distinct types of lymphoma,
      lung carcinoma, and neuroblastoma. The aberrant ALK expression in nonneural cells
      results from chromosomal translocations that create novel fusion proteins. These
      protein hybrids compose the proximal part of a partner gene, including its
      promoter region, and the distal part of ALK, including the coding sequence for
      the entire kinase domain. ALK was first identified in a subset of T-cell
      lymphomas with anaplastic large cell lymphoma (ALCL) morphology (ALK+ ALCL), the
      vast majority of which harbor the well-characterized nucleophosmin (NPM)-ALK
      fusion protein. NPM-ALK co-opts several intracellular signal transduction
      pathways, foremost being the STAT3 pathway, normally activated by cytokines from
      the interleukin-2 (IL-2) family to promote cell proliferation and to inhibit
      apoptosis. Many genes and proteins modulated by NPM-ALK are also involved in
      evasion of antitumor immune response, protection from hypoxia, angiogenesis, DNA
      repair, cell migration and invasiveness, and cell metabolism. In addition, NPM
      ALK uses epigenetic silencing mechanisms to downregulate tumor suppressor genes
      to maintain its own expression. Importantly, NPM-ALK is capable of transforming
      primary human CD4+ T cells into immortalized cell lines indistinguishable from
      patient-derived ALK+ ALCL. Preliminary clinical studies indicate that inhibition
      of NPM-ALK induces long-lasting complete remissions in a large subset of heavily
      pretreated adult patients and the vast majority of children with high-stage ALK+
      ALCL. Combining ALK inhibition with other novel therapeutic modalities should
      prove even more effective.

PMID- 27879261
TI  - Limited linkages of aboveground and belowground phenology: A study in grape.
AB  - PREMISE OF THE STUDY: Plant phenology influences resource utilization, carbon
      fluxes, and interspecific interactions. Although controls on aboveground
      phenology have been studied to some degree, controls on root phenology are
      exceptionally poorly understood. METHODS: We used minirhizotrons to examine the
      timing of grape root production over 5 yr in Fredonia, New York, USA, in a humid
      continental climate; and over 3 yr in Oakville, California, USA, in a
      Mediterranean climate. We used data from previous experiments to examine the
      relationship of root phenology with aboveground phenology. We compared
      interannual variability in root and shoot growth and determined the influence of
      abiotic factors on the timing of root initiation, peak root standing crop, peak
      root growth rate, and cessation of root growth. KEY RESULTS: Root phenology was
      not tightly coupled with aboveground phenological periods. Both sites typically
      had one yearly root flush and high interannual variability in root growth. Root
      phenology was more variable in California than in New York. In this and other
      published studies, interannual variation in root phenology was greater than
      variation in aboveground phenology. The three phenological phases of root growth
      root initiation, peak root growth, and root cessation-were related to different
      suites of abiotic factors. CONCLUSIONS: Root phenology is highly variable among
      years. Analysis of potential controlling factors over several years suggest that
      belowground phenological phases should be analyzed separately from each other. If
      aboveground grape phenology responds differently than belowground phenology to
      changes in air temperature, global warming may further uncouple the timing of
      aboveground and belowground growth.

PMID- 27879259
TI  - Unexpected role for p19INK4d in posttranscriptional regulation of GATA1 and
      modulation of human terminal erythropoiesis.
AB  - Terminal erythroid differentiation is tightly coordinated with cell-cycle exit,
      which is regulated by cyclins, cyclin-dependent kinases, and cyclin-dependent
      kinase inhibitors (CDKI), yet their roles in erythropoiesis remain to be fully
      defined. We show here that p19INK4d, a member of CDKI family, is abundantly
      expressed in erythroblasts and that p19INK4d knockdown delayed erythroid
      differentiation, inhibited cell growth, and led to increased apoptosis and
      generation of abnormally nucleated late-stage erythroblasts. Unexpectedly,
      p19INK4d knockdown did not affect cell cycle. Rather, it led to decreased
      expression of GATA1 protein. Importantly, the differentiation and nuclear defects
      were rescued by ectopic expression of GATA1. Because the GATA1 protein is
      protected by nuclear heat shock protein family (HSP) member HSP70, we examined
      the effects of p19INK4d knockdown on HSP70 and found that p19INK4d knockdown led
      to decreased expression of HSP70 and its nuclear localization. The reduced levels
      of HSP70 are the result of reduced extracellular signal-regulated kinase (ERK)
      activation. Further biochemical analysis revealed that p19INK4d directly binds to
      Raf kinase inhibitor PEBP1 and that p19INK4d knockdown increased the expression
      of PEBP1, which in turn led to reduced ERK activation. Thus we have identified an
      unexpected role for p19INK4d via a novel PEBP1-p-ERK-HSP70-GATA1 pathway. These
      findings are likely to have implications for improved understanding of disordered
      erythropoiesis.

PMID- 27879260
TI  - Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota.
AB  - Bone marrow suppression is an adverse effect associated with many antibiotics,
      especially when administered for prolonged treatment courses. Recent advances in
      our understanding of steady-state hematopoiesis have allowed us to explore the
      effects of antibiotics on hematopoietic progenitors in detail using a murine
      model. Antibiotic-treated mice exhibited anemia, thrombocytosis, and leukopenia,
      with pronounced pan-lymphopenia as demonstrated by flow cytometric analysis of
      peripheral blood. Bone marrow progenitor analysis revealed depletion of
      hematopoietic stem cells and multipotent progenitors across all subtypes.
      Granulocytes and B cells were also diminished in the bone marrow, whereas the
      number of CD8+ T cells increased. Reductions in progenitor activity were not
      observed when cells were directly incubated with antibiotics, suggesting that
      these effects are indirect. Hematopoietic changes were associated with a
      significant contraction of the fecal microbiome and were partially rescued by
      fecal microbiota transfer. Further, mice raised in germ-free conditions had
      hematopoietic abnormalities similar to those seen in antibiotic-treated mice, and
      antibiotic therapy of germ-free mice caused no additional abnormalities. The
      effects of antibiotics were phenocopied in Stat1-deficient mice, with no
      additional suppression by antibiotics in these mice. We conclude that microbiome
      depletion as a result of broad-spectrum antibiotic treatment disrupts basal Stat1
      signaling and alters T-cell homeostasis, leading to impaired progenitor
      maintenance and granulocyte maturation. Methods to preserve the microbiome may
      reduce the incidence of antibiotic-associated bone marrow suppression.

PMID- 27879262
TI  - Influence of biological and social-historical variables on the time taken to
      describe an angiosperm.
AB  - PREMISE OF THE STUDY: By convention, scientific naming of angiosperm species
      began in 1753; it is estimated that 10-20% of species remain undescribed. To
      complete this task before rare, undescribed species go extinct, a better
      understanding of the description process is needed. The South American Cerrado
      biodiversity hotspot was considered a suitable model due to a high diversity of
      plants, habitats, and social history of species description. METHODS: A
      randomized sample of 214 species (2% of the angiosperm flora) and 22 variables
      were analyzed using multivariate analyses and analysis of variance. KEY RESULTS:
      Plants with wide global distributions, recorded from many areas, and above 2.6 m
      were described significantly earlier than narrowly distributed, uncommon species
      of smaller stature. The beginning of the career of the botanist who first
      collected the species was highly significant, with an average delay between first
      collection and description of 29 yr, and between type collection and description
      19 yr; standard deviations were high and rose over time. Over a third of first
      collections were not cited in descriptions. Trends such as scientific
      specialization and decline of undescribed species were highlighted. Descriptions
      that involved potential collaboration between collectors and authors were
      significantly slower than those that did not. CONCLUSIONS: Results support four
      recommendations to hasten discovery of new species: (1) preferential collecting
      of plants below 2.6 m, at least in the Cerrado; (2) access to undetermined
      material in herbaria; (3) fieldwork in areas where narrow-endemic species occur;
      (4) fieldwork by knowledgeable botanists followed by descriptive activity by the
      same.

PMID- 27879264
TI  - Differential Regulation of the Melanoma Proteome by eIF4A1 and eIF4E.
AB  - Small molecules and antisense oligonucleotides that inhibit the translation
      initiation factors eIF4A1 and eIF4E have been explored as broad-based therapeutic
      agents for cancer treatment, based on the frequent upregulation of these two
      subunits of the eIF4F cap-binding complex in many cancer cells. Here, we provide
      support for these therapeutic approaches with mechanistic studies of eIF4F-driven
      tumor progression in a preclinical model of melanoma. Silencing eIF4A1 or eIF4E
      decreases melanoma proliferation and invasion. There were common effects on the
      level of cell-cycle proteins that could explain the antiproliferative effects in
      vitro Using clinical specimens, we correlate the common cell-cycle targets of
      eIF4A1 and eIF4E with patient survival. Finally, comparative proteomic and
      transcriptomic analyses reveal extensive mechanistic divergence in response to
      eIF4A1 or eIF4E silencing. Current models indicate that eIF4A1 and eIF4E function
      together through the 5'UTR to increase translation of oncogenes. In contrast, our
      data demonstrate that the common effects of eIF4A1 and eIF4E on translation are
      mediated by the coding region and 3'UTR. Moreover, their divergent effects occur
      through the 5'UTR. Overall, our work shows that it will be important to evaluate
      subunit-specific inhibitors of eIF4F in different disease contexts to fully
      understand their anticancer actions. Cancer Res; 77(3); 613-22. (c)2016 AACR.

PMID- 27879265
TI  - IL6 Signaling in Peripheral Blood T Cells Predicts Clinical Outcome in Breast
      Cancer.
AB  - IL6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties,
      which acts directly on cancer cells to promote their survival and proliferation.
      Elevated serum IL6 levels negatively correlate with survival of cancer patients,
      which is generally attributed to the direct effects of IL6 on cancer cells. How
      IL6 modulates the host immune response in cancer patients is unclear. Here, we
      show the IL6 signaling response in peripheral blood T cells is impaired in breast
      cancer patients and is associated with blunted Th17 differentiation. The
      mechanism identified involved downregulation of gp130 and IL6Ralpha in breast
      cancer patients and was independent of plasma IL6 levels. Importantly, defective
      IL6 signaling in peripheral blood T cells at diagnosis correlated with worse
      relapse-free survival. These results indicate that intact IL6 signaling in T
      cells is important for controlling cancer progression. Furthermore, they
      highlight a potential for IL6 signaling response in peripheral blood T cells at
      diagnosis as a predictive biomarker for clinical outcome of breast cancer
      patients. Cancer Res; 77(5); 1119-26. (c)2016 AACR.

PMID- 27879266
TI  - Threshold Analysis and Biodistribution of Fluorescently Labeled Bevacizumab in
      Human Breast Cancer.
AB  - In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical
      guidance for cancer therapy as well as create opportunities to directly observe
      cancer biology in patients. However, malignant and nonmalignant tissues are
      usually distinguished on fluorescence images by applying empirically determined
      fluorescence intensity thresholds. Here, we report the development of fSTREAM, a
      set of analytic methods designed to streamline the analysis of surgically excised
      breast tissues by collecting and statistically processing hybrid multiscale
      fluorescence, color, and histology readouts toward precision fluorescence
      imaging. fSTREAM addresses core questions of how to relate fluorescence intensity
      to tumor tissue and how to quantitatively assign a normalized threshold that
      sufficiently differentiates tumor tissue from healthy tissue. Using fSTREAM we
      assessed human breast tumors stained in vivo with fluorescent bevacizumab at
      microdose levels. Showing that detection of such levels is achievable, we
      validated fSTREAM for high-resolution mapping of the spatial pattern of labeled
      antibody and its relation to the underlying cancer pathophysiology and tumor
      border on a per patient basis. We demonstrated a 98% sensitivity and 79%
      specificity when using labeled bevacizumab to outline the tumor mass. Overall,
      our results illustrate a quantitative approach to relate fluorescence signals to
      malignant tissues and improve the theranostic application of fluorescence
      molecular imaging. Cancer Res; 77(3); 623-31. (c)2016 AACR.

PMID- 27879267
TI  - Pifithrin-MU Prevents Cisplatin-Induced Chemobrain by Preserving Neuronal
      Mitochondrial Function.
AB  - Cognitive impairment, termed chemobrain, is a common neurotoxicity associated
      with chemotherapy treatment, affecting an estimated 78% of patients. Prompted by
      the hypothesis that neuronal mitochondrial dysfunction underlies chemotherapy
      induced cognitive impairment (CICI), we explored the efficacy of administering
      the small-molecule pifithrin (PFT)-MU, an inhibitor of mitochondrial p53
      accumulation, in preventing CICI. Male C57BL/6J mice injected with cisplatin +/-
      PFT-MU for two 5-day cycles were assessed for cognitive function using novel
      object/place recognition and alternation in a Y-maze. Cisplatin impaired
      performance in the novel object/place recognition and Y-maze tests. PFT-MU
      treatment prevented CICI and associated cisplatin-induced changes in coherency of
      myelin basic protein fibers in the cingular cortex and loss of doublecortin+
      cells in the subventricular zone and hippocampal dentate gyrus. Mechanistically,
      cisplatin decreased spare respirator capacity of brain synaptosomes and caused
      abnormal mitochondrial morphology, which was counteracted by PFT-MU
      administration. Notably, increased mitochondrial p53 did not lead to cerebral
      caspase-3 activation or cytochrome-c release. Furthermore, PFT-MU administration
      did not impair the anticancer efficacy of cisplatin and radiotherapy in tumor
      bearing mice. Our results supported the hypothesis that neuronal mitochondrial
      dysfunction induced by mitochondrial p53 accumulation is an underlying cause of
      CICI and that PFT-MU may offer a tractable therapeutic strategy to limit this
      common side-effect of many types of chemotherapy. Cancer Res; 77(3); 742-52.
      (c)2016 AACR.

PMID- 27879269
TI  - Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T
      Cells.
AB  - Elevated numbers of regulatory T cells (Treg) in patient tumors are known to
      inhibit efficient antitumor T-cell responses. To study the mechanisms controlling
      tumor rejection, we assessed different mouse models for Treg depletion. In
      Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in
      complete rejection of transplanted HCmel12 melanomas in a CD8+ T-cell-dependent
      way. In contrast, about 90% Treg depletion obtained in BAC transgenic
      Foxp3.LuciDTR4 mice failed to induce complete rejection of HCmel12 melanomas,
      demonstrating that residual Tregs were able to control CD8+ T-cell responses
      against the tumor. Ninety-nine percent of Treg depletion provoked drastic changes
      in the tumor microenvironment, such as strong infiltration of CD8+ T cells and
      basophils. Intratumoral basophils enhanced CD8+ T-cell infiltration via
      production of chemokines CCL3 and CCL4; antibody-based blocking of these
      chemokines inhibited CD8+ T-cell infiltration. Therapeutic induction of
      basophilia by IL3/anti-IL3 antibody complexes, combined with transfer of CD8+ T
      cells, resulted in enhanced T-cell infiltration and tumor rejection. Our study
      identifies a critical role basophils play in tumor rejection and that this role
      can be exploited for therapeutic intervention. Cancer Res; 77(2); 291-302.
      (c)2016 AACR.

PMID- 27879268
TI  - Transcriptional Selectivity of Epigenetic Therapy in Cancer.
AB  - A central challenge in the development of epigenetic cancer therapy is the
      ability to direct selectivity in modulating gene expression for disease-selective
      efficacy. To address this issue, we characterized by RNA-seq, DNA methylation,
      and ChIP-seq analyses the epigenetic response of a set of colon, breast, and
      leukemia cancer cell lines to small-molecule inhibitors against DNA
      methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases
      (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2
      inhibitor GSK343). We also characterized the effects of DAC as combined with the
      other compounds. Averaged over the cancer cell models used, we found that DAC
      affected 8.6% of the transcriptome and that 95.4% of the genes affected were
      upregulated. DAC preferentially regulated genes that were silenced in cancer and
      that were methylated at their promoters. In contrast, Depsi affected the
      expression of 30.4% of the transcriptome but showed little selectivity for gene
      upregulation or silenced genes. S2101, UNC0638, and GSK343 affected only 2% of
      the transcriptome, with UNC0638 and GSK343 preferentially targeting genes marked
      with H3K9me2 or H3K27me3, respectively. When combined with histone methylase
      inhibitors, the extent of gene upregulation by DAC was extended while still
      maintaining selectivity for DNA-methylated genes and silenced genes. However, the
      genes upregulated by combination treatment exhibited limited overlap, indicating
      the possibility of targeting distinct sets of genes based on different epigenetic
      therapy combinations. Overall, our results demonstrated that DNA
      methyltransferase inhibitors preferentially target cancer-relevant genes and can
      be combined with inhibitors targeting histone methylation for synergistic effects
      while still maintaining selectivity. Cancer Res; 77(2); 470-81. (c)2016 AACR.

PMID- 27879271
TI  - Vitamin D3 Prevents Calcium-Induced Progression of Early-Stage Prostate Tumors by
      Counteracting TRPC6 and Calcium Sensing Receptor Upregulation.
AB  - Active surveillance has emerged as an alternative to immediate treatment for men
      with low-risk prostate cancer. Accordingly, identification of environmental
      factors that facilitate progression to more aggressive stages is critical for
      disease prevention. Although calcium-enriched diets have been speculated to
      increase prostate cancer risk, their impact on early-stage tumors remains
      unexplored. In this study, we addressed this issue with a large interventional
      animal study. Mouse models of fully penetrant and slowly evolving prostate
      tumorigenesis showed that a high calcium diet dramatically accelerated the
      progression of prostate intraepithelial neoplasia, by promoting cell
      proliferation, micro-invasion, tissue inflammation, and expression of
      acknowledged prostate cancer markers. Strikingly, dietary vitamin D prevented
      these calcium-triggered tumorigenic effects. Expression profiling and in vitro
      mechanistic studies showed that stimulation of PC-3 cells with extracellular Ca2+
      resulted in an increase in cell proliferation rate, store-operated calcium entry
      (SOCE) amplitude, cationic channel TRPC6, and calcium sensing receptor (CaSR)
      expression. Notably, administration of the active vitamin D metabolite calcitriol
      reversed all these effects. Silencing CaSR or TRPC6 expression in calcium
      stimulated PC3 cells decreased cell proliferation and SOCE. Overall, our results
      demonstrate the protective effects of vitamin D supplementation in blocking the
      progression of early-stage prostate lesions induced by a calcium-rich diet.
      Cancer Res; 77(2); 355-65. (c)2016 AACR.

PMID- 27879270
TI  - Breast Cancer Resistance to Antiestrogens Is Enhanced by Increased ER Degradation
      and ERBB2 Expression.
AB  - Endocrine therapies effectively improve the outcomes of patients with estrogen
      receptor (ER)-positive breast cancer. However, the emergence of drug-resistant
      tumors creates a core clinical challenge. In breast cancer cells rendered
      resistant to the antiestrogen fulvestrant, we defined causative mechanistic roles
      for the transcription factor YBX1 and the levels of ER and the ERBB2 receptor.
      Enforced expression of YBX1 in parental cells conferred resistance against
      tamoxifen and fulvestrant in vitro and in vivo Furthermore, YBX1 overexpression
      was associated with decreased and increased levels of ER and ERBB2 expression,
      respectively. In antiestrogen-resistant cells, increased YBX1 phosphorylation was
      associated with a 4-fold higher degradation rate of ER. Notably, YBX1 bound the
      ER, leading to its accelerated proteasomal degradation, and induced the
      transcriptional activation of ERBB2. In parallel fashion, tamoxifen treatment
      also augmented YBX1 binding to the ERBB2 promoter to induce increased ERBB2
      expression. Together, these findings define a mechanism of drug resistance
      through which YBX1 contributes to antiestrogen bypass in breast cancer cells.
      Cancer Res; 77(2); 545-56. (c)2016 AACR.

PMID- 27879272
TI  - Quantification of Pathway Cross-talk Reveals Novel Synergistic Drug Combinations
      for Breast Cancer.
AB  - Combinatorial therapeutic approaches are an imperative to improve cancer
      treatment, because it is critical to impede compensatory signaling mechanisms
      that can engender drug resistance to individual targeted drugs. Currently
      approved drug combinations result largely from empirical clinical experience and
      cover only a small fraction of a vast therapeutic space. Here we present a
      computational network biology approach, based on pathway cross-talk inhibition,
      to discover new synergistic drug combinations for breast cancer treatment. In
      silico analysis identified 390 novel anticancer drug pairs belonging to 10 drug
      classes that are likely to diminish pathway cross-talk and display synergistic
      antitumor effects. Ten novel drug combinations were validated experimentally, and
      seven of these exhibited synergy in human breast cancer cell lines. In
      particular, we found that one novel combination, pairing the estrogen response
      modifier raloxifene with the c-Met/VEGFR2 kinase inhibitor cabozantinib,
      dramatically potentiated the drugs' individual antitumor effects in a mouse model
      of breast cancer. When compared with high-throughput combinatorial studies
      without computational prioritization, our approach offers a significant advance
      capable of uncovering broad-spectrum utility across many cancer types. Cancer
      Res; 77(2); 459-69. (c)2016 AACR.

PMID- 27879273
TI  - Seeing and Sampling the Surface of the Atherosclerotic Plaque: Red or White Can
      Make Blue.

PMID- 27879274
TI  - Cortactin in Atherosclerosis: Just Say NO.

PMID- 27879276
TI  - Novel Therapeutic Targets of Pulmonary Hypertension.

PMID- 27879275
TI  - Von Willebrand Factor and ADAMTS13: Too Much or Too Little of a Good Thing?

PMID- 27879278
TI  - Formation of Functional Conduction Block During the Onset of Reentrant
      Ventricular Tachycardia.

PMID- 27879277
TI  - Eukaryotic translation initiation factor 5A2 promotes metabolic reprogramming in
      hepatocellular carcinoma cells.
AB  - Reprogramming of intracellular metabolism is common in liver cancer cells.
      Understanding the mechanisms of cell metabolic reprogramming may present a new
      basis for liver cancer treatment. In our previous study, we reported that a novel
      oncogene eukaryotic translation initiation factor 5A2 (EIF5A2) promotes
      tumorigenesis under hypoxic condition. Here, we aim to investigate the role of
      EIF5A2 in cell metabolic reprogramming during hepatocellular carcinoma (HCC)
      development. In this study, we reported that the messenger RNA (mRNA) level of
      EIF5A2 was upregulated in 59 of 105 (56.2%) HCC clinical samples (P = 0.015), and
      EIF5A2 overexpression was significantly associated with shorter survival time of
      patients with HCC (P = 0.021). Ectopic expression of EIF5A2 in HCC cell lines
      significantly promoted cell growth and accelerated glucose utilization and
      lipogenesis rates. The high rates of glucose uptake and lactate secretion
      conferred by EIF5A2 revealed an abnormal activity of aerobic glycolysis in HCC
      cells. Several key enzymes involved in glycolysis including glucose transporter
      type 1 and 2, hexokinase 2, phosphofructokinase liver type, glyceraldehyde 3
      phosphate dehydrogenase, pyruvate kinase M2 isoform, phosphoglycerate mutase 1
      and lactate dehydrogenase A were upregulated by overexpression of EIF5A2.
      Moreover, EIF5A2 showed positive correlations with FASN and ACSS2, two key
      enzymes involved in the fatty acid de novo biosynthetic pathway, at both protein
      and mRNA levels in HCC. These results indicated that EIF5A2 may regulate fatty
      acid de novo biosynthesis by increasing the uptake of acetate. In conclusion, our
      findings demonstrate that EIF5A2 has a critical role in HCC cell metabolic
      reprogramming and may serve as a prominent novel therapeutic target for liver
      cancer treatment.

PMID- 27879279
TI  - Heart Rate Turbulence Is a Powerful Predictor of Cardiac Death and Ventricular
      Arrhythmias in Postmyocardial Infarction and Heart Failure Patients: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Heart rate turbulence (HRT) has been proposed as a candidate marker
      of altered autonomic tone, and some studies showed its prognostic value for both
      cardiac death (CD) and sudden death. Nevertheless, HRT is not currently used in
      the clinical practice. METHODS AND RESULTS: We performed a systematic review and
      meta-analysis of the predictive value of HRT for the end points of total
      mortality, CD, and fatal and nonfatal ventricular arrhythmias in postacute
      myocardial infarction and heart failure patients. MEDLINE and The Cochrane
      Library databases were systematically searched to identify studies, which
      analyzed the predictive value of abnormal HRT for the defined end points. Twenty
      studies (25 cohorts: 12 832 patients) were identified by the systematic review,
      and 15 studies (20 cohorts: 11 499 patients) were included in the meta-analyses.
      Abnormal HRT was a predictive marker for all the end points in heart failure
      patients and more markedly in postacute myocardial infarction patients, where 9
      out of the 10 cohorts had an ejection fraction >30%. In postacute myocardial
      infarction patients, HRT had pooled risk ratios of 3.53 (95% confidence interval
      [CI], 2.54-4.90), 4.82 (95% CI, 3.12-7.45), and 4.48 (95% CI, 3.04-6.60), and
      positive likelihood ratios of 3.5 (95% CI, 2.6-4.8), 4.1 (95% CI, 3.0-5.7), and
      2.7 (95% CI, 2.2-3.3) for total mortality, CD, and arrhythmic events,
      respectively. The combination of abnormal HRT and T-wave alternans (5 cohorts:
      1516 patients) increased the predictive power for CD and arrhythmic events.
      CONCLUSIONS: HRT is a powerful predictor of both CD and arrhythmic events,
      particularly in postacute myocardial infarction patients with ejection fraction
      >30%. HRT power increases in combination with T-wave alternans analysis.

PMID- 27879281
TI  - Retraction.

PMID- 27879280
TI  - Fifteen-minute consultation: the complexities of empirical antibiotic selection
      for serious bacterial infections-a practical approach.
AB  - Potentially life-threatening infections require immediate antibiotic therapy.
      Most early stage antibiotic treatment for these infections is empirical, that is,
      covering a range of possible target bacteria while awaiting culture results.
      Empirical antibiotic regimens need to reflect the epidemiology of most likely
      causative bacteria, type of infection and patient risk factors. Summary data from
      relevant isolates in similar patients help to identify appropriate empirical
      regimens. At present, such data are mostly presented as hospital or other
      aggregate antibiograms, showing antimicrobial susceptibility testing results by
      bacterial species. However, a more suitable method is to calculate weighted
      incidence syndromic combination antibiograms for different types of infections
      and regimens, allowing head-to-head comparisons of empirical regimens. Once there
      is confirmatory or negative microbiological evidence of infection, empirical
      regimens should be adapted to the identified bacterial species and
      susceptibilities or discontinued.

PMID- 27879282
TI  - Sex-Related Discordance Between Aortic Valve Calcification and Hemodynamic
      Severity of Aortic Stenosis: Is Valvular Fibrosis the Explanation?
AB  - RATIONALE: Calcific aortic stenosis (AS) is characterized by calcium deposition
      in valve leaflets. However, women present lower aortic valve calcification loads
      than men for the same AS hemodynamic severity. OBJECTIVE: We, thus, aimed to
      assess sex differences in aortic valve fibrocalcific remodeling. METHODS AND
      RESULTS: One hundred and twenty-five patients underwent Doppler echocardiography
      and multidetector computed tomography within 3 months before aortic valve
      replacement. Explanted stenotic tricuspid aortic valves were weighed, and
      fibrosis degree was determined. Sixty-four men and 39 women were frequency
      matched for age, body mass index, hypertension, renal disease, diabetes mellitus,
      and AS severity. Mean age (75+/-9 years), mean gradient (41+/-18 mm Hg), and
      indexed aortic valve area (0.41+/-0.12 cm2/m2) were similar between men and women
      (all P>=0.18). Median aortic valve calcification (1973 [1124-3490] Agatston
      units) and mean valve weight (2.36+/-0.99 g) were lower in women compared with
      men (both P<0.0001). Aortic valve calcification density correlated better with
      valve weight in men (r2=0.57; P<0.0001) than in women (r2=0.26; P=0.0008). After
      adjustment for age, body mass index, aortic valve calcification density, and
      aortic annulus diameter, female sex was an independent risk factor for higher
      fibrosis score in AS valves (P=0.003). Picrosirius red staining of explanted
      valves showed greater amount of collagen fibers (P=0.01), and Masson trichrome
      staining revealed a greater proportion of dense connective tissue (P=0.02) in
      women compared with men. CONCLUSIONS: In this series of patients with tricuspid
      aortic valve and similar AS severity, women have less valvular calcification but
      more fibrosis compared with men. These findings suggest that the pathophysiology
      of AS and thus potential targets for drug development may be different according
      to sex.

PMID- 27879283
TI  - Infant Videofluoroscopic Swallow Study Testing, Swallowing Interventions, and
      Future Acute Respiratory Illness.
AB  - OBJECTIVES: Tube feedings are commonly prescribed to infants with swallowing
      abnormalities detected by videofluoroscopic swallow study (VFSS), but there are
      no studies demonstrating efficacy of these interventions to reduce risk of acute
      respiratory illness (ARI). We sought to measure the association between
      swallowing interventions and future ARI, among VFSS-tested infants. METHODS:
      Retrospective cohort of all infants (<12 months) tested with VFSS at a children's
      hospital between January 1, 2010, and January 1, 2012. Hospital ARI encounters
      (emergency, observation, or inpatient status) in a 22-hospital integrated health
      care delivery system, between the first VFSS and age 3 years, were measured. VFSS
      results were grouped by normal, intermediate, and oropharyngeal aspiration (OPA),
      with OPA further subdivided by silent versus cough and thin versus thick liquid
      OPA. Cox regression modeled the association between swallowing interventions
      (thickened or nasal tube feedings) and ARI, accounting for changes in swallowing
      and interventions over time. RESULTS: 576 infants were tested with a VFSS in
      their first year of life, receiving a total of 1051 VFSSs in their first 3 years
      of life. More than 60% of infants received a measured feeding intervention. With
      the exception of infants with silent OPA who received thickened feedings, neither
      thickening nor nasal tube feedings, compared with no intervention, were
      associated with a decreased risk of subsequent ARI. CONCLUSIONS: Swallowing
      interventions and repeated testing are common among VFSS-tested infants. However,
      the importance of diagnosing and intervening on VFSS-detected swallowing
      abnormalities for the majority of tested infants remains unclear.

PMID- 27879285
TI  - Telephone delivery of interpersonal psychotherapy by certified nurse-midwives may
      help reduce symptoms of postpartum depression.

PMID- 27879284
TI  - Seipin regulates ER-lipid droplet contacts and cargo delivery.
AB  - Seipin is an endoplasmic reticulum (ER) membrane protein implicated in lipid
      droplet (LD) biogenesis and mutated in severe congenital lipodystrophy (BSCL2).
      Here, we show that seipin is stably associated with nascent ER-LD contacts in
      human cells, typically via one mobile focal point per LD Seipin appears critical
      for such contacts since ER-LD contacts were completely missing or morphologically
      aberrant in seipin knockout and BSCL2 patient cells. In parallel, LD mobility was
      increased and protein delivery from the ER to LDs to promote LD growth was
      decreased. Moreover, while growing LDs normally acquire lipid and protein
      constituents from the ER, this process was compromised in seipin-deficient cells.
      In the absence of seipin, the initial synthesis of neutral lipids from exogenous
      fatty acid was normal, but fatty acid incorporation into neutral lipids in cells
      with pre-existing LDs was impaired. Together, our data suggest that seipin helps
      to connect newly formed LDs to the ER and that by stabilizing ER-LD contacts
      seipin facilitates the incorporation of protein and lipid cargo into growing LDs
      in human cells.

PMID- 27879286
TI  - Staffing and nurse-perceived quality of care.

PMID- 27879287
TI  - Tissue-specific programming of memory CD8 T cell subsets impacts protection
      against lethal respiratory virus infection.
AB  - How tissue-specific anatomical distribution and phenotypic specialization are
      linked to protective efficacy of memory T cells against reinfection is unclear.
      Here, we show that lung environmental cues program recently recruited central
      like memory cells with migratory potentials for their tissue-specific functions
      during lethal respiratory virus infection. After entering the lung, some central
      like cells retain their original CD27hiCXCR3hi phenotype, enabling them to
      localize near the infected bronchiolar epithelium and airway lumen to function as
      the first line of defense against pathogen encounter. Others, in response to
      local cytokine triggers, undergo a secondary program of differentiation that
      leads to the loss of CXCR3, migration arrest, and clustering within
      peribronchoarterial areas and in interalveolar septa. Here, the immune system
      adapts its response to prevent systemic viral dissemination and mortality. These
      results reveal the striking and unexpected spatial organization of central-
      versus effector-like memory cells within the lung and how cooperation between
      these two subsets contributes to host defense.

PMID- 27879289
TI  - Remote multifocal bleeding points producing a Sylvian subpial hematoma during
      endovascular coiling of an acutely ruptured cerebral aneurysm.
AB  - Subpial hematoma is a rare type of intracranial hemorrhage with a poor prognosis.
      A new mechanism to explain subpial Sylvian hematoma formation in acute post
      aneurysmal subarachnoid hemorrhage (SAH) was observed during coiling of a
      posterior communicating artery aneurysm. Multiple small bleeding points from pial
      branches of the left middle cerebral artery, which were remote from the ruptured
      aneurysm, were observed on conventional angiography. This bleeding led to the
      formation of a large expanding subpial Sylvian hematoma. Similar observations
      have been recently demonstrated on 4D CT angiography (4D CTA). We present a case
      that adds evidence to the literature in support of a new mechanism of subpial
      hematoma formation in the setting of acute SAH. This may advocate the early use
      of 4D CTA and conveys a poor prognosis, which might influence treatment
      decisions.

PMID- 27879290
TI  - The Moderating Influences of Retirement Transition, Age, and Gender on Daily
      Stressors and Psychological Distress.
AB  - This study investigated the influences of retirement transition, age, and gender
      on aspects of daily experiences in adults (aged 50-75 years) who stayed working (
      n = 138) and who transitioned into retirement ( n = 72). Data derived from the
      first and second waves of the Daily Diary Study of the National Survey of Midlife
      in the United States. Participants completed telephone interviews about their
      experiences across eight consecutive days. Findings showed a significant
      interaction effect of retirement transition and age on daily stressors. Gender
      did not significantly moderate the associations between retirement transition and
      daily experiences. These findings suggest that retirement transition must be
      considered in the context of life course influences, especially age, to better
      determine the quality of daily experiences of midlife and older adults, and these
      life course influences should be considered in programs and services aimed to
      help adults navigate the retirement experiences.

PMID- 27879291
TI  - In a challenging environment, intelligent use of surveillance data can help guide
      sexual health commissioners' choices to maximise public health benefit.

PMID- 27879288
TI  - Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ
      Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic
      Melanoma.
AB  - Pathophysiologies of cancer-associated syndromes such as cachexia are poorly
      understood and no routine biomarkers have been established, yet. Using shotgun
      proteomics, known marker molecules including PMEL, CRP, SAA, and CSPG4 were found
      deregulated in patients with metastatic melanoma. Targeted analysis of 58
      selected proteins with multiple reaction monitoring was applied for independent
      data verification. In three patients, two of which suffered from cachexia, a
      tissue damage signature was determined, consisting of nine proteins, PLTP, CD14,
      TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44, and C4A, as well as increased levels of
      glycine and asparagine, and decreased levels of polyunsaturated
      phosphatidylcholine concentrations, as determined by targeted metabolomics.
      Remarkably, these molecules are known to be involved in key processes of cancer
      cachexia. Based on these results, we propose a model how metastatic melanoma may
      lead to reprogramming of organ functions via formation of platelet activating
      factors from long-chain polyunsaturated phosphatidylcholines under oxidative
      conditions and via systemic induction of intracellular calcium mobilization.
      Calcium mobilization in platelets was demonstrated to alter levels of several of
      these marker molecules. Additionally, platelets from melanoma patients proved to
      be in a rather exhausted state, and platelet-derived eicosanoids implicated in
      tumor growth were found massively increased in blood from three melanoma
      patients. Platelets were thus identified as important source of serum protein and
      lipid alterations in late stage melanoma patients. As a result, the proposed
      model describes the crosstalk between lipolysis of fat tissue and muscle wasting
      mediated by oxidative stress, resulting in the metabolic deregulations
      characteristic for cachexia.

PMID- 27879292
TI  - Autonomy, age and sterilisation requests.
AB  - Sterilisation requests made by young, child-free adults are frequently denied by
      doctors, despite sterilisation being legally available to individuals over the
      age of 18. A commonly given reason for denied requests is that the patient will
      later regret their decision. In this paper, I examine whether the possibility of
      future regret is a good reason for denying a sterilisation request. I argue that
      it is not and hence that decision-competent adults who have no desire to have
      children should have their requests approved. It is a condition of being
      recognised as autonomous that a person ought to be permitted to make decisions
      that they might later regret, provided that their decision is justified at the
      time that it is made. There is also evidence to suggest that sterilisation
      requests made by men are more likely to be approved than requests made by women,
      even when age and number of children are factored in. This may indicate that
      attitudes towards sterilisation are influenced by gender discourses that define
      women in terms of reproduction and mothering. If this is the case, then it is
      unjustified and should be addressed. There is no good reason to judge people's
      sterilisation requests differently in virtue of their gender.

PMID- 27879293
TI  - Living with the animals: animal or robotic companions for the elderly in smart
      homes?
AB  - Although the use of pet robots in senior living facilities and day-care centres,
      particularly for individuals suffering from dementia, has been intensively
      researched, the question of introducing pet robots into domestic settings has
      been relatively neglected. Ambient assisted living (AAL) offers many interface
      opportunities for integrating motorised companions. There are diverse medical
      reasons, as well as arguments from animal ethics, that support the use of pet
      robots in contrast to living with live animals. However, as this paper makes
      clear, we should not lose sight of the option of living with animals at home for
      as long as possible and in conformity with the welfare of the animal assisted by
      AAL technology.

PMID- 27879294
TI  - CXCR2 is involved in pulmonary intravascular macrophage accumulation and
      angiogenesis in a rat model of hepatopulmonary syndrome.
AB  - Hepatopulmonary syndrome (HPS) is a lung complication in various liver diseases,
      with high incidence, poor prognosis and no effective non-surgical treatments in
      patients with hepatocirrhosis. Therefore, assessing HPS pathogenesis to explore
      proper therapy strategies is clinically relevant. In the present study, male
      Sprague-Dawley rats underwent sham operation or common bile duct ligation (CBDL).
      Two weeks post-surgery, the following groups were set up for 2 weeks of
      treatment: sham + normal saline, CBDL + CXCR2 antagonist SB225002, CBDL + tumour
      necrosis factor alpha (TNF-alpha) antagonist PTX and CBDL + normal saline groups.
      Liver and lung tissues were collected after mean arterial pressure (MAP) and
      portal venous pressure (PVP) measurements. Haematoxylin and eosin (H&E) staining
      (lung) and Masson staining (liver) were performed for pathological analyses.
      Finally, pulmonary tissue RNA and total protein were assessed for target
      effectors. The mRNA and protein levels of CXCR2 were significantly increased in
      the pulmonary tissue of CBDL rats. What's more, CXCR2 inhibition by SB225002
      reduced the expression of CD68 and von Willebrand factor (vWf) in CBDL rats.
      Importantly, CXCR2 inhibition suppressed the activation of Akt and extracellular
      signal-regulated kinase (ERK) in CBDL rats. Antagonization of TNF-alpha with PTX
      down-regulated the expression of CXCR2. During HPS pathogenesis in rats, CXCR2
      might be involved in the accumulation of pulmonary intravascular macrophages and
      angiogenesis, possibly by activating Akt and ERK, with additional regulation by
      TNF-alpha that enhanced pulmonary angiogenesis by directly acting on the
      pulmonary tissue. Finally, the present study may provide novel targets for the
      treatment of HPS.

PMID- 27879295
TI  - Evaluating Coincident Relationships Between Obesity Incidence and Normal Weight
      Incidence From Birth Through Kindergarten for US Children.
AB  - PURPOSE: We examine the concurrent relationship between obesity incidence and
      normal weight status incidence and prevalence in children between 9 months and
      kindergarten. DESIGN: Multistage, probability sample from the Early Childhood
      Longitudinal Study-Birth cohort. SETTING: United States. PARTICIPANTS:
      Representative sample of US preschool children (n = 9950) followed from birth
      through kindergarten. MEASURES: From direct, anthropometric measures, we reported
      prevalence and incidence rates across 4 follow-up periods. ANALYSIS: In addition
      to prevalence and incidence rates, we reported risk ratios based on multiple
      definitions and estimated predicted probabilities of obesity and normal weight
      status using clinically meaningful body mass index (BMI)-for-age percentiles.
      RESULTS: Obesity prevalence (13%-20%) was much smaller than normal weight status
      prevalence (66%-70%). Lower socioeconomic status, Hispanic, and non-Hispanic
      black children had greater risk of obesity. During 9 months to kindergarten,
      obesity incidence decreased two-thirds (15.6%), while normal weight status
      incidence decreased almost one-half (44.6%). Coincidently, normal weight status
      incidence (ranged from 23% to 45%) was consistently and substantially higher than
      obesity incidence (ranged from 5% to 15%). During 4 years to kindergarten, the
      obesity risk for overweight children was 13 times higher than that for normal
      weight status children. CONCLUSION: Overall rates of obese and normal weight
      incidence were substantial at 9 months, trended lower, but remained high through
      kindergarten. At 4 years to kindergarten, children with relatively high initial
      BMI were very likely to become obese but far less likely to achieve normal weight
      status.

PMID- 27879296
TI  - Elevated Modified Shock Index Within 24 Hours of ICU Admission Is an Early
      Indicator of Mortality in the Critically Ill.
AB  - PURPOSE: To assess whether exposure to modified shock index (MSI) in the first 24
      hours of intensive care unit (ICU) admission is associated with increased in
      hospital mortality. METHODS: Adult critically ill patients were included in a
      case-control design with 1:2 matching. Cases (death) and controls (alive) were
      abstracted by a reviewer blinded to exposure status (MSI). Cases were matched to
      controls on 3 factors-age, end-stage renal disease, and ICU admission diagnosis.
      RESULTS: Eighty-three cases and 159 controls were included. On univariate
      analysis, lorazepam administration (odds ratio [OR]: 5.75, confidence interval
      [CI] = 2.28-14.47; P <= .01), shock requiring vasopressors (OR: 3.62, CI = 1.77
      7.40; P <= .01), maximum MSI (OR: 2.77 per unit, CI = 1.63-4.71; P <= .001), and
      elevated acute physiologic and chronic health evaluation (APACHE) III score at 1
      hour (OR: 1.41 per 10 units, CI = 1.19-1.66; P <= .001) were associated with
      mortality. Maximum MSI (OR: 1.93 per unit, CI = 1.07-3.48, P = .03) and APACHE
      III score at 1 hour (OR: 1.29 per 10 units, CI = 1.09-1.53; P = .003) remained
      significant with mortality in the multivariate analysis. The optimal cutoff point
      for high MSI and mortality was 1.8. CONCLUSION: Critically ill patients who
      demonstrate an elevated MSI within the first 24 hours of ICU admission have a
      significant mortality risk. Given that MSI is easily calculated at the bedside,
      clinicians may institute interventions earlier which could improve survival.

PMID- 27879297
TI  - Addressing the Mental Health Needs of Latino Children in Immigrant Families.
AB  - Latino children in the United States, whether immigrants themselves or children
      in immigrant families, are at high risk for mental health disorders stemming from
      poverty, exposure to trauma, assimilation stressors, and discrimination. The
      timely identification and treatment of mental health disorders in Latino children
      are compromised by limited healthcare access and quality as well as the lack of
      routine mental health screening in pediatric primary care. Here we review Spanish
      language validity and implementation studies of Bright Futures previsit mental
      health screening tools and models of care. We identify strengths and weaknesses
      in the literature and suggest tools for use in mental health care assessment,
      management, and treatment for Latino children in pediatric primary care.
      Pediatricians can improve care of Latino children through awareness of risk
      factors for mental health disorders, integration of evidence-based screening
      tools, and advocacy for culturally tailored mental health resources.

PMID- 27879298
TI  - Withdrawals and Retirements in Professional Tennis Players.
AB  - BACKGROUND: Injuries and illnesses for professional tennis athletes disrupt
      training, competition, and progression in the sport and represent a major reason
      for athlete withdrawal or retirement from a tournament. Few descriptive
      epidemiological studies have focused on these trends in elite tennis athletes.
      PURPOSE: To examine the causes of professional tennis player withdrawal or
      retirement from United States Tennis Association (USTA) Pro Circuit tournaments
      during 2013. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE:
      Level 4. METHODS: Tournament records from the 2013 USTA Pro Circuit season were
      retrospectively reviewed for incidences of injury and illness that resulted in
      athlete withdrawal from the tournament. Data were reported as incidence rates per
      1000 match exposures and rate ratios. RESULTS: There were 70 medical conditions
      over the course of 27 competitions (20,988 match exposures), for an overall
      incidence rate of 3.34 per 1000 match exposures. Women were more likely to injure
      themselves on clay courts compared with hard courts (rate ratio, 4.67; 95%
      confidence interval [CI], 1.41-19.85) and in the first half of the season
      compared with the second half (rate ratio, 3.95; 95% CI, 1.13-21.17). Men had a
      higher injury rate than women (rate ratio, 1.88; 95% CI, 1.17-3.63), and muscle
      /tendon-related injuries were 6 times more likely than all other injuries (95%
      CI, 2.81-14.69). CONCLUSION: Women were more likely to experience an injury when
      playing on clay court surfaces, and they also experienced more injuries during
      the first half of the season. Injury rates for men often peaked during the months
      that players could qualify for Grand Slam competitions. There was a predominance
      of injuries in men compared with women.

PMID- 27879300
TI  - Bladder explosion, a rare complication following transurethral resection of the
      prostate.
AB  - We present a man aged 69 years who suffered from bladder explosion during
      transurethral resection of the prostate. Exploratory laparotomy was performed and
      the bladder was primarily repaired with running sutures. This patient was
      discharged without symptoms of urinary dysfunction on day 8 after operation. We
      provide prevention methods that can decrease the risk of this important
      complication.

PMID- 27879299
TI  - Return to Golf After Lumbar Fusion.
AB  - BACKGROUND: Spinal fusion surgery is being increasingly performed, yet few
      studies have focused on return to recreational sports after lumbar fusion and
      none have specifically analyzed return to golf. HYPOTHESIS: Most golfers
      successfully return to sport after lumbar fusion surgery. STUDY DESIGN: Case
      series. LEVEL OF EVIDENCE: Level 4. METHODS: All patients who underwent 1- or 2
      level primary lumbar fusion surgery for degenerative pathologies performed by a
      single surgeon between January 2008 and October 2012 and had at least 1-year
      follow-up were included. Patients completed a specifically designed golf survey.
      Surveys were mailed, given during follow-up clinic, or answered during telephone
      contact. RESULTS: A total of 353 patients met the inclusion and exclusion
      criteria, with 200 responses (57%) to the questionnaire producing 34 golfers. The
      average age of golfers was 57 years (range, 32-79 years). In 79% of golfers,
      preoperative back and/or leg pain significantly affected their ability to play
      golf. Within 1 year from surgery, 65% of patients returned to practice and 52%
      returned to course play. Only 29% of patients stated that continued back/leg pain
      limited their play. Twenty-five patients (77%) were able to play the same amount
      of golf or more than before fusion surgery. Of those providing handicaps, 12
      (80%) reported the same or an improved handicap. CONCLUSION: More than 50% of
      golfers return to on-course play within 1 year of lumbar fusion surgery. The
      majority of golfers can return to preoperative levels in terms of performance
      (handicap) and frequency of play. CLINICAL RELEVANCE: This investigation offers
      insight into when golfers return to sport after lumbar fusion surgery and
      provides surgeons with information to set realistic expectations postoperatively.

PMID- 27879301
TI  - Primary lymphoma of the uterine cervix: a rare constellation of symptoms.

PMID- 27879302
TI  - Neonatal osteomyelitis of the first rib causing lung abscess.
AB  - Rib osteomyelitis (OM) is a rare disease that occurs in ~1% or less of all
      haematogenous OM. Acute OM of the rib has rarely been reported and its treatment
      is difficult. Prompt recognition and aggressive treatment will reduce mortality
      and morbidity in a new born.

PMID- 27879303
TI  - Smooth muscle tumour of uncertain malignant potential (SMTUMP) in the nasal
      cavity: an incidental finding.
AB  - Sino-nasal smooth muscle tumours of uncertain malignant potential (SMTUMP) are
      very rare neoplasms of mesenchymal origin with features in between a benign
      leiomyoma and a leiomyosarcoma. We report a rare case of SMTUMP in a 44-year-old
      woman, who presented with vague symptoms of pharyngitis. Nasal endoscopy revealed
      a smooth mass in left nasal cavity. Contrast-enhanced CT and MRI scans showed
      features likely to be inverted papilloma or olfactory neuroblastoma or
      meningioma. Excision was planned and intraoperatively, frozen section revealed a
      probable spindle cell lesion. Final histopathological report following
      immunohistochemistry (IHC) & immunofluoresence (IF) confirmed it to be a SMTUMP.
      This patient underwent complete resection via endoscopic KTP laser assisted,
      anterior skull base surgery with no recurrence on follow-up.

PMID- 27879304
TI  - Aortic valve fibroelastoma: a rare cause of stroke.
AB  - The prevalence of primary cardiac tumours varies from 0.02% to 0.45%. Cardiac
      papillary fibroelastoma (CPF) is a rare tumour diagnosed incidentally on imaging.
      The clinical manifestations result from thromboembolisation and include transient
      ischaemic attack, stroke and sudden cardiac death. We present a patient aged 57
      years with CPF arising from the aortic valve. The patient presented with right
      hemiparesis due to acute stroke. He received tissue plasminogen activator with
      complete resolution of neurological symptoms. Echocardiography revealed a broad
      based, gelatinous, non-mobile mass on the left aortic cusp. The tumour was
      excised sparing the aortic valve. The patient recovered rapidly without any
      complications. The histopathological examination confirmed the diagnosis of CPF.
      A review of the literature suggests that CPF is a rare but treatable cause of
      stroke. The course is not clear and there are no tumours or patient-related
      characteristics which could predict the risk of thromboembolisation. Surgical
      treatment is definite and is relatively safe.

PMID- 27879305
TI  - Partial segmental thrombosis of the corpus cavernosum presenting with perineal
      pain.
AB  - We describe the case of a man aged 43 years who presented with a 2-week history
      of a palpable lump in the right proximal penile shaft. This was preceded by a 6
      month history of perineal pain, accompanied by erectile dysfunction. An urgent
      MRI scan of his penis identified a thrombus within the right crus and corpus of
      the penis. His thrombophilia screen was normal. The patient was started on oral
      anticoagulation and a phosphodiesterase inhibitor (PDE-5i) to prevent thrombus
      progression and maintain erectile function. At 5 months, the patients' symptoms
      had resolved and an MRI showed a reduction in the thrombus size. MRI is a useful
      imaging modality to diagnose a thrombus within the corpus cavernosum in patients
      presenting with a history of penile and perineal pain together with a palpable
      lump. The non-enhancement of the lesion helps to differentiate this from
      alternative rare lesions within the penis and perineum.

PMID- 27879307
TI  - Unusual cause of profound weight loss in a young woman.
AB  - A 27-year-old woman presented with anorexia, weight loss and psychiatric symptoms
      for the past 4 years. She did not have history of headache, visual disturbances
      or symptoms of raised intracranial pressure. She was sarcopenic with body mass
      index of 10.16 kg/m2Her systemic examination was normal except for temporal
      hemianopia suggesting a sellar/suprasellar lesion. Hormonal evaluation revealed
      pan-hypopituitarism with central diabetes insipidus. Subsequent neuroimaging
      revealed sellar-suprasellar mass lesion with intense contrast enhancement and
      leptomeningeal metastases. Cerebrospinal fluid analysis showed elevated beta
      human chorionic gonadotropin and the presence of syncytiotrophoblast germ cells.
      Histopathology from the mass lesion confirmed the diagnosis of germinoma.
      Immunohistochemistry of the tumour tissue was positive for c-kit and placental
      alkaline phosphatise. She received a combination of chemotherapy with
      craniospinal irradiation. Significant weight loss in a young woman may not always
      be an eating disorder like anorexia nervosa albeit more common than germ cell
      tumour.

PMID- 27879306
TI  - Symmetrical digital gangrene after a high dose intravenous infusion of
      epinephrine and dopamine following resuscitation from cardiac arrest.

PMID- 27879308
TI  - Rare cause of arterial hypertension.

PMID- 27879310
TI  - Large thymoma mass invading cardiac structures.

PMID- 27879309
TI  - Brief episodes of non-specific psychosis later diagnosed as periodic catatonia.
AB  - A 73-year-old woman was known to have discrete episodes of psychosis not
      otherwise specified that would require a brief admission to hospital and total
      remission following a short course of benzodiazepine or antipsychotic treatment.
      She had no underlying schizophrenic or affective disorder and was completely
      unimpaired in between episodes, which could last several years. She presented to
      us with psychotic symptoms but also noted to have many catatonic features, which
      were also present on previous presentations. Following failure with antipsychotic
      trials on this index presentation, she completely remitted with a short course of
      electroconvulsive therapy. We discuss the importance of identifying and treating
      catatonia and the lesser-known variant of periodic catatonia. Current
      presentations should always take into account the lifetime context of psychiatric
      illness. Rarely do patients with primary psychotic disorders not have any
      impairment or treatment in between episodes.

PMID- 27879311
TI  - Ascites and adnexal masses: not always ovarian or tubal carcinoma.

PMID- 27879312
TI  - Association of peripheral differential leukocyte counts with dyslipidemia risk in
      Chinese patients with hypertension: insight from the China Stroke Primary
      Prevention Trial.
AB  - The aim of the present study was to examine the association between peripheral
      differential leukocyte counts and dyslipidemia in a Chinese hypertensive
      population. A total of 10,866 patients with hypertension were enrolled for a
      comprehensive assessment of cardiovascular risk factors using data from the China
      Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte,
      neutrophil, and lymphocyte counts were determined according to standard methods.
      Peripheral differential leukocyte counts were consistently and positively
      associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG
      levels (all P < 0.001 for trend), while inversely associated with HDL cholesterol
      levels (P < 0.05 for trend). In subsequent analyses where serum lipids were
      dichotomized (dyslipidemia/normolipidemia), we found that patients in the highest
      quartile of total leukocyte count (>=7.6 * 109 cells/l) had 1.64 times the risk
      of high TG [95% confidence interval (CI): 1.46, 1.85], 1.34 times the risk of
      high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI:
      1.12, 1.39) compared with their counterparts in the lowest quartile of total
      leukocyte count. Similar patterns were also observed with neutrophils and
      lymphocytes. In summary, these findings indicate that elevated differential
      leukocyte counts are directly associated with serum lipid levels and increased
      odds of dyslipidemia.

PMID- 27879313
TI  - International Registry of Patients Carrying TGFBR1 or TGFBR2 Mutations: Results
      of the MAC (Montalcino Aortic Consortium).
AB  - BACKGROUND: The natural history of aortic diseases in patients with TGFBR1 or
      TGFBR2 mutations reported by different investigators has varied greatly. In
      particular, the current recommendations for the timing of surgical repair of the
      aortic root aneurysms may be overly aggressive. METHODS AND RESULTS: The
      Montalcino Aortic Consortium, which includes 15 centers worldwide that specialize
      in heritable thoracic aortic diseases, was used to gather data on 441 patients
      from 228 families, with 176 cases harboring a mutation in TGBR1 and 265 in
      TGFBR2. Patients harboring a TGFBR1 mutation have similar survival rates (80%
      survival at 60 years), aortic risk (23% aortic dissection and 18% preventive
      aortic surgery), and prevalence of extra-aortic features (29% hypertelorism, 53%
      cervical arterial tortuosity, and 27% wide scars) when compared with patients
      harboring a TGFBR2 mutation. However, TGFBR1 males had a greater aortic risk than
      females, whereas TGFBR2 males and females had a similar aortic risk.
      Additionally, aortic root diameter prior to or at the time of type A aortic
      dissection tended to be smaller in patients carrying a TGFBR2 mutation and was
      <=45 mm in 6 women with TGFBR2 mutations, presenting with marked systemic
      features and low body surface area. Aortic dissection was observed in 1.6% of
      pregnancies. CONCLUSIONS: Patients with TGFBR1 or TGFBR2 mutations show the same
      prevalence of systemic features and the same global survival. Preventive aortic
      surgery at a diameter of 45 mm, lowered toward 40 in females with low body
      surface area, TGFBR2 mutation, and severe extra-aortic features may be
      considered.

PMID- 27879314
TI  - Genetic Variation in the SLC8A1 Calcium Signaling Pathway Is Associated With
      Susceptibility to Kawasaki Disease and Coronary Artery Abnormalities.
AB  - BACKGROUND: Kawasaki disease (KD) is an acute pediatric vasculitis in which host
      genetics influence both susceptibility to KD and the formation of coronary artery
      aneurysms. Variants discovered by genome-wide association studies and linkage
      studies only partially explain the influence of genetics on KD susceptibility.
      METHODS AND RESULTS: To search for additional functional genetic variation, we
      performed pathway and gene stability analysis on a genome-wide association study
      data set. Pathway analysis using European genome-wide association study data
      identified 100 significantly associated pathways (P<5*10-4). Gene stability
      selection identified 116 single nucleotide polymorphisms in 26 genes that were
      responsible for driving the pathway associations, and gene ontology analysis
      demonstrated enrichment for calcium transport (P=1.05*10-4). Three single
      nucleotide polymorphisms in solute carrier family 8, member 1 (SLC8A1), a
      sodium/calcium exchanger encoding NCX1, were validated in an independent Japanese
      genome-wide association study data set (meta-analysis P=0.0001). Patients
      homozygous for the A (risk) allele of rs13017968 had higher rates of coronary
      artery abnormalities (P=0.029). NCX1, the protein encoded by SLC8A1, was
      expressed in spindle-shaped and inflammatory cells in the aneurysm wall.
      Increased intracellular calcium mobilization was observed in B cell lines from
      healthy controls carrying the risk allele. CONCLUSIONS: Pathway-based association
      analysis followed by gene stability selection proved to be a valuable tool for
      identifying risk alleles in a rare disease with complex genetics. The role of
      SLC8A1 polymorphisms in altering calcium flux in cells that mediate coronary
      artery damage in KD suggests that this pathway may be a therapeutic target and
      supports the study of calcineurin inhibitors in acute KD.

PMID- 27879316
TI  - Structure-based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit
      Neutralizing Antibodies.
AB  - A major goal for HIV-1 vaccine development is an ability to elicit strong and
      durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope
      glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that
      are susceptible to bNAbs isolated from infected individuals. Nonetheless, all
      trimeric and monomeric Env immunogens designed to date have failed to elicit such
      antibodies. We report the structure-guided design of HIV-1 cyclically permuted
      gp120 that forms homogeneous, stable trimers, and displays enhanced binding to
      multiple bNAbs, including VRC01, VRC03, VRC-PG04, PGT128, and the quaternary
      epitope-specific bNAbs PGT145 and PGDM1400. Constructs that were cyclically
      permuted in the V1 loop region and contained an N-terminal trimerization domain
      to stabilize V1V2-mediated quaternary interactions, showed the highest
      homogeneity and the best antigenic characteristics. In guinea pigs, a DNA prime
      protein boost regimen with these new gp120 trimer immunogens elicited potent
      neutralizing antibody responses against highly sensitive Tier 1A isolates and
      weaker neutralizing antibody responses with an average titer of about 115 against
      a panel of heterologous Tier 2 isolates. A modest fraction of the Tier 2 virus
      neutralizing activity appeared to target the CD4 binding site on gp120. These
      results suggest that cyclically permuted HIV-1 gp120 trimers represent a viable
      platform in which further modifications may be made to eventually achieve
      protective bNAb responses.

PMID- 27879315
TI  - Monoubiquitination Inhibits the Actin Bundling Activity of Fascin.
AB  - Fascin is an actin bundling protein that cross-links individual actin filaments
      into straight, compact, and stiff bundles, which are crucial for the formation of
      filopodia, stereocillia, and other finger-like membrane protrusions. The
      dysregulation of fascin has been implicated in cancer metastasis, hearing loss,
      and blindness. Here we identified monoubiquitination as a novel mechanism that
      regulates fascin bundling activity and dynamics. The monoubiquitination sites
      were identified to be Lys247 and Lys250, two residues located in a positive
      charge patch at the actin binding site 2 of fascin. Using a chemical
      ubiquitination method, we synthesized chemically monoubiquitinated fascin and
      determined the effects of monoubiquitination on fascin bundling activity and
      dynamics. Our data demonstrated that monoubiquitination decreased the fascin
      bundling EC50, delayed the initiation of bundle assembly, and accelerated the
      disassembly of existing bundles. By analyzing the electrostatic properties on the
      solvent-accessible surface of fascin, we proposed that monoubiquitination
      introduced steric hindrance to interfere with the interaction between actin
      filaments and the positively charged patch at actin binding site 2. We also
      identified Smurf1 as a E3 ligase regulating the monoubiquitination of fascin. Our
      findings revealed a previously unidentified regulatory mechanism for fascin,
      which will have important implications for the understanding of actin bundle
      regulation under physiological and pathological conditions.

PMID- 27879317
TI  - Correlated evolution between CK1delta Protein and the Serine-rich Motif
      Contributes to Regulating the Mammalian Circadian Clock.
AB  - Understanding the mechanism underlying the physiological divergence of species is
      a long-standing issue in evolutionary biology. The circadian clock is a highly
      conserved system existing in almost all organisms that regulates a wide range of
      physiological and behavioral events to adapt to the day-night cycle. Here, the
      interactions between hCK1epsilon/delta/DBT (Drosophila ortholog of
      CK1delta/epsilon) and serine-rich (SR) motifs from hPER2 (ortholog of Drosophila
      per) were reconstructed in a Drosophila circadian system. The results indicated
      that in Drosophila, the SR mutant form hPER2S662G does not recapitulate the mouse
      or human mutant phenotype. However, introducing hCK1delta (but not DBT) shortened
      the circadian period and restored the SR motif function. We found that hCK1delta
      is catalytically more efficient than DBT in phosphorylating the SR motif, which
      demonstrates that the evolution of CK1delta activity is required for SR motif
      modulation. Moreover, an abundance of phosphorylatable SR motifs and the striking
      emergence of putative SR motifs in vertebrate proteins were observed, which
      provides further evidence that the correlated evolution between kinase activity
      and its substrates set the stage for functional diversity in vertebrates. It is
      possible that such correlated evolution may serve as a biomarker associated with
      the adaptive benefits of diverse organisms. These results also provide a concrete
      example of how functional synthesis can be achieved through introducing
      evolutionary partners in vivo.

PMID- 27879318
TI  - Inactivation of Regulatory-associated Protein of mTOR (Raptor)/Mammalian Target
      of Rapamycin Complex 1 (mTORC1) Signaling in Osteoclasts Increases Bone Mass by
      Inhibiting Osteoclast Differentiation in Mice.
AB  - Mammalian target of rapamycin complex 1 (mTORC1) is involved in anabolic
      metabolism in both osteoblasts and chondrocytes, but the role of mTORC1 in
      osteoclast biology in vivo remains to be elucidated. In this study, we showed
      that deletion of regulatory-associated protein of mTOR (Raptor) in osteoclasts
      led to an increase in bone mass with decreased bone resorption. Raptor-deficient
      bone marrow-derived macrophages exhibited lower mTORC1-S6K1 signaling and
      retarded osteoclast differentiation, as determined by the number of osteoclasts,
      tartrate-resistant acid phosphatase activity, and expression of osteoclast
      specific genes. Enforced expression of constitutively active S6K1 rescued the
      impaired osteoclast differentiation in Raptor-deficient bone marrow-derived
      macrophages. Furthermore, pharmacological inhibition of mTORC1 signaling by
      rapamycin could also inhibit osteoclast differentiation and osteoclast-specific
      gene expression. Taken together, our findings demonstrate that mTORC1 plays a key
      role in the network of catabolic bone resorption in osteoclasts and may serve as
      a potential pharmacological target for the regulation of osteoclast activity in
      bone metabolic disorders.

PMID- 27879320
TI  - The Relationship Between Mental Representations of Welfare Recipients and
      Attitudes Toward Welfare.
AB  - Scholars have argued that opposition to welfare is, in part, driven by
      stereotypes of African Americans. This argument assumes that when individuals
      think about welfare, they spontaneously think about Black recipients. We
      investigated people's mental representations of welfare recipients. In Studies 1
      and 2, we used a perceptual task to visually estimate participants' mental
      representations of welfare recipients. Compared with the average non-welfare
      recipient image, the average welfare-recipient image was perceived (by a separate
      sample) as more African American and more representative of stereotypes
      associated with welfare recipients and African Americans. In Study 3,
      participants were asked to determine whether they supported giving welfare
      benefits to the people pictured in the average welfare-recipient and non-welfare
      recipient images generated in Study 2. Participants were less supportive of
      giving welfare benefits to the person shown in the welfare-recipient image than
      to the person shown in the non-welfare-recipient image. The results suggest that
      mental images of welfare recipients may bias attitudes toward welfare policies.

PMID- 27879321
TI  - When Misinformation Improves Memory.
AB  - In two experiments, we explored the effects of noticing and remembering change in
      the misinformation paradigm. People watched slide shows, read narratives
      containing misinformation about the events depicted in the slide shows, and took
      a recognition test on which they reported whether any details had changed between
      the slides and the narratives. As expected, we found a strong misinformation
      effect overall. In some cases, however, misinformation led to improved
      recognition, which is opposite the usual finding. Critically, misinformation led
      to improved recognition of the original event when subjects detected and
      remembered a change between the original event and the postevent information. Our
      research agrees with other findings from retroactive-interference paradigms and
      can be interpreted within the recursive-remindings framework, according to which
      detecting and remembering change can enhance retention. We conclude that the
      misinformation effect occurs mostly for witnessed details that are not
      particularly memorable. In the case of more memorable details, providing
      misinformation can actually facilitate later recollection of the original events.

PMID- 27879322
TI  - The Whole Warps the Sum of Its Parts.
AB  - The efficiency of averaging properties of sets without encoding redundant details
      is analogous to gestalt proposals that perception is parsimoniously organized as
      a function of recurrent order in the world. This similarity suggests that
      grouping and averaging are part of a broader set of strategies allowing the
      visual system to circumvent capacity limitations. To examine how gestalt grouping
      affects the manner in which information is averaged and remembered, I compared
      the error in observers' adjustments of remembered sizes of individual circles in
      two different mean-size sets defined by similarity, proximity, connectedness, or
      a common region. Overall, errors were more similar within the same gestalt
      defined groups than between different gestalt-defined groups, such that the
      remembered sizes of individual circles were biased toward the mean size of their
      respective gestalt-defined groups. These results imply that gestalt grouping
      facilitates perceptual averaging to minimize the error with which individual
      items are encoded, thereby optimizing the efficiency of visual short-term memory.

PMID- 27879319
TI  - AMP-activated Kinase (AMPK) Promotes Innate Immunity and Antiviral Defense
      through Modulation of Stimulator of Interferon Genes (STING) Signaling.
AB  - The host protein Stimulator of Interferon Genes (STING) has been shown to be
      essential for recognition of both viral and intracellular bacterial pathogens,
      but its regulation remains unclear. Previously, we reported that mitochondrial
      membrane potential regulates STING-dependent IFN-beta induction independently of
      ATP synthesis. Because mitochondrial membrane potential controls calcium
      homeostasis, and AMP-activated protein kinase (AMPK) is regulated, in part, by
      intracellular calcium, we postulated that AMPK participates in STING activation;
      however, its role has yet to be been defined. Addition of an intracellular
      calcium chelator or an AMPK inhibitor to either mouse macrophages or mouse
      embryonic fibroblasts (MEFs) suppressed IFN-beta and TNF-alpha induction
      following stimulation with the STING-dependent ligand 5,6-dimethyl xanthnone-4
      acetic acid (DMXAA). These pharmacological findings were corroborated by showing
      that MEFs lacking AMPK activity also failed to up-regulate IFN-beta and TNF-alpha
      after treatment with DMXAA or the natural STING ligand cyclic GMP-AMP (cGAMP). As
      a result, AMPK-deficient MEFs exhibit impaired control of vesicular stomatitis
      virus (VSV), a virus sensed by STING that can cause an influenza-like illness in
      humans. This impairment could be overcome by pretreatment of AMPK-deficient MEFs
      with type I IFN, illustrating that de novo production of IFN-beta in response to
      VSV plays a key role in antiviral defense during infection. Loss of AMPK also led
      to dephosphorylation at Ser-555 of the known STING regulator, UNC-51-like kinase
      1 (ULK1). However, ULK1-deficient cells responded normally to DMXAA, indicating
      that AMPK promotes STING-dependent signaling independent of ULK1 in mouse cells.

PMID- 27879323
TI  - Issues and Challenges in Diagnostic Sequencing for Inherited Cardiac Conditions.
AB  - BACKGROUND: Inherited cardiac conditions are a relatively common group of
      Mendelian diseases associated with ill health and death, often in the young.
      Research into the genetic causes of these conditions has enabled confirmatory and
      predictive diagnostic sequencing to become an integral part of the clinical
      management of inherited cardiomyopathies, arrhythmias, aortopathies, and
      dyslipidemias. CONTENT: Currently, the principle benefit of clinical genetic
      testing is the cascade screening of family members of patients with a pathogenic
      variant, enabling targeted follow up of presymptomatic genotype-positive
      individuals and discharge of genotype-negative individuals to health. For the
      affected proband, diagnostic sequencing can also be useful in discriminating
      inherited disease from alternative diagnoses, directing treatment, and for
      molecular autopsy in cases of sudden unexplained death. Advances in sequencing
      technology have expanded testing panels for inherited cardiac conditions and
      driven down costs, further improving the cost-effectiveness of genetic testing.
      However, this expanded testing requires great rigor in the identification of
      pathogenic variants, with domain-specific knowledge required for variant
      interpretation. SUMMARY: Diagnostic sequencing has the potential to become an
      integral part of the clinical management of patients with inherited cardiac
      conditions. However, to move beyond just confirmatory and predictive testing, a
      much greater understanding is needed of the genetic basis of these conditions,
      the role of the environment, and the underlying disease mechanisms. With this
      additional information it is likely that genetic testing will increasingly be
      used for stratified and preventative strategies in the era of genomic medicine.

PMID- 27879324
TI  - The Changing Face of HDL and the Best Way to Measure It.
AB  - BACKGROUND: HDL cholesterol (HDL-C) is a commonly used lipid biomarker for
      assessing cardiovascular health. While a central focus has been placed on the
      role of HDL in the reverse cholesterol transport (RCT) process, our appreciation
      for the other cardioprotective properties of HDL continues to expand with further
      investigation into the structure and function of HDL and its specific
      subfractions. The development of novel assays is empowering the research
      community to assess different aspects of HDL function, which at some point may
      evolve into new diagnostic tests. CONTENT: This review discusses our current
      understanding of the formation and maturation of HDL particles via RCT, as well
      as the newly recognized roles of HDL outside RCT. The antioxidative,
      antiinflammatory, antiapoptotic, antithrombotic, antiinfective, and
      vasoprotective effects of HDL are all discussed, as are the related methodologies
      for assessing these different aspects of HDL function. We elaborate on the
      importance of protein and lipid composition of HDL in health and disease and
      highlight potential new diagnostic assays based on these parameters. SUMMARY:
      Although multiple epidemiologic studies have confirmed that HDL-C is a strong
      negative risk marker for cardiovascular disease, several clinical and
      experimental studies have yielded inconsistent results on the direct role of HDL
      C as an antiatherogenic factor. As of yet, our increased understanding of HDL
      biology has not been translated into successful new therapies, but will
      undoubtedly depend on the development of alternative ways for measuring HDL
      besides its cholesterol content.

PMID- 27879325
TI  - Cushing syndrome in a child due to pro-opiomelanocortin (POMC) secretion from a
      yolk sac tumor.
AB  - CONTEXT: Pituitary microadenomas and adrenal tumours are the most common causes
      for endogenous Cushing syndrome (CS) in children. CASE DESCRIPTION: We describe a
      two-year old girl with Cushing syndrome due to ectopic pro-opiomelanocortin
      (POMC) production from an abdominal yolk sac tumor. Cortisol concentrations were
      elevated but adrenocorticotropic hormone (ACTH) concentrations were equivocal.
      The use of antibodies specifically detecting ACTH precursors revealed that plasma
      ACTH precursors were elevated. Additionally, an ACTH assay with a low cross
      reactivity for precursors showed low concentrations of ACTH. Immunohistochemistry
      suggested POMC but not ACTH production by the tumour. CONCLUSION: We describe a
      yolk sac tumour as a novel source of ectopic POMC production leading to CS in a
      young girl.

PMID- 27879326
TI  - Effects of levothyroxine treatment on pregnancy outcomes in pregnant women with
      autoimmune thyroid disease.
AB  - BACKGROUND: Despite some studies indicating that thyroid antibody positivity
      during pregnancy has been associated with adverse pregnancy outcomes, evidence
      regarding the effects of levothyroxine (LT4) treatment of euthyroid/subclinical
      hypothyroid pregnant women with autoimmune thyroid disease on pregnancy outcome
      is limited. We aimed to assess whether pregnant women with autoimmune thyroid
      disease, but without overt thyroid dysfunction are affected by higher rates of
      adverse pregnancy outcomes. In addition, we aimed to explore whether LT4
      treatment improves the pregnancy outcome of affected women. METHODS: A
      prospective study was carried out on pregnant women from the first trimester to
      delivery. The study was conducted among pregnant women receiving prenatal care in
      centers under coverage of Shahid Beheshti University of Medical Sciences. Of a
      total of 1746 pregnant women, screened for thyroid dysfunction, 1028 euthyroid
      TPOAb-negative (TPOAb-) and 131 thyroid peroxidase antibody-positive (TPOAb+)
      women without overt thyroid dysfunction entered the second phase of the study.
      TPOAb+ women were randomly divided into two groups: group A (n = 65), treated
      with LT4 and group B (n = 66), received no treatment. The 1028 TPOAb- women
      (group C) served as a normal population control group. Primary outcomes were
      preterm delivery and miscarriage and secondary outcomes included placenta
      abruption, still birth, neonatal admission and neonatal TSH levels. RESULTS:
      Groups A and C displayed a lower rate of preterm deliveries compared with group B
      (RR = 0.30, 95% CI: 0.1-0.85, P = 0.0229) and (RR = 0.23, 95% CI: 0.14-0.40, P <
      0.001) respectively. There was no statistically significant difference in the
      rates of preterm labor between groups A and C (RR = 0.79, 95% CI: 0.30-2.09, P =
      0.64). The number needed to treat (NNT) for preterm birth was 5.9 (95% CI: 3.33
      25.16). CONCLUSIONS: Treatment with LT4 decreases the risk of preterm delivery in
      women who are positive for TPOAb.

PMID- 27879330
TI  - Quantitative Transcriptomics Reveals the Growth- and Nutrient-Dependent Response
      of a Streamlined Marine Methylotroph to Methanol and Naturally Occurring
      Dissolved Organic Matter.
AB  - The members of the OM43 clade of Betaproteobacteria are abundant coastal
      methylotrophs with a range of carbon-utilizing capabilities. However, their
      underlying transcriptional and metabolic responses to shifting conditions or
      different carbon substrates remain poorly understood. We examined the
      transcriptional dynamics of OM43 isolate NB0046 subjected to various inorganic
      nutrient, vitamin, and carbon substrate regimes over different growth phases to
      (i) develop a quantitative model of its mRNA content; (ii) identify
      transcriptional markers of physiological activity, nutritional state, and carbon
      and energy utilization; and (iii) identify pathways involved in methanol or
      naturally occurring dissolved organic matter (DOM) metabolism. Quantitative
      transcriptomics, achieved through addition of internal RNA standards, allowed for
      analyses on a transcripts-per-cell scale. This streamlined bacterium exhibited
      substantial shifts in total mRNA content (ranging from 1,800 to 17 transcripts
      cell-1 in the exponential and deep stationary phases, respectively) and gene
      specific transcript abundances (>1,000-fold increases in some cases), depending
      on the growth phase and nutrient conditions. Carbon metabolism genes exhibited
      substantial dynamics, including those for ribulose monophosphate, tricarboxylic
      acid (TCA), and proteorhodopsin, as well as methanol dehydrogenase (xoxF), which,
      while always the most abundant transcript, increased from 5 to 120 transcripts
      cell-1 when cultures were nutrient and vitamin amended. In the DOM treatment,
      upregulation of TCA cycle, methylcitrate cycle, vitamin, and organic phosphorus
      genes suggested a metabolic route for this complex mixture of carbon substrates.
      The genome-wide inventory of transcript abundances produced here provides insight
      into a streamlined marine bacterium's regulation of carbon metabolism and energy
      flow, providing benchmarks for evaluating the activity of OM43 populations in
      situ IMPORTANCE: Bacteria exert a substantial influence on marine organic matter
      flux, yet the carbon components targeted by specific bacterial groups, as well as
      how those groups' metabolic activities change under different conditions, are not
      well understood. Gene expression studies of model organisms can identify these
      responses under defined conditions, which can then be compared to environmental
      transcriptomes to elucidate in situ activities. This integration, however, is
      limited by the data's relative nature. Here, we report the fully quantitative
      transcriptome of a marine bacterium, providing a genome-wide survey of cellular
      transcript abundances and how they change with different states of growth,
      nutrient conditions, and carbon substrates. The results revealed the dynamic
      metabolic strategies this methylotroph has for processing both simple one-carbon
      compounds and the complex multicarbon substrates of naturally derived marine
      organic matter and provide baseline quantitative data for identifying their in
      situ activities and impact on the marine carbon cycle.

PMID- 27879329
TI  - Phenotypic Profiling Reveals that Candida albicans Opaque Cells Represent a
      Metabolically Specialized Cell State Compared to Default White Cells.
AB  - : The white-opaque switch is a bistable, epigenetic transition affecting multiple
      traits in Candida albicans including mating, immunogenicity, and niche
      specificity. To compare how the two cell states respond to external cues, we
      examined the fitness, phenotypic switching, and filamentation properties of white
      cells and opaque cells under 1,440 different conditions at 25 degrees C and 37
      degrees C. We demonstrate that white and opaque cells display striking
      differences in their integration of metabolic and thermal cues, so that the two
      states exhibit optimal fitness under distinct conditions. White cells were fitter
      than opaque cells under a wide range of environmental conditions, including
      growth at various pHs and in the presence of chemical stresses or antifungal
      drugs. This difference was exacerbated at 37 degrees C, consistent with white
      cells being the default state of C. albicans in the mammalian host. In contrast,
      opaque cells showed greater fitness than white cells under select nutritional
      conditions, including growth on diverse peptides at 25 degrees C. We further
      demonstrate that filamentation is significantly rewired between the two states,
      with white and opaque cells undergoing filamentous growth in response to distinct
      external cues. Genetic analysis was used to identify signaling pathways impacting
      the white-opaque transition both in vitro and in a murine model of commensal
      colonization, and three sugar sensing pathways are revealed as regulators of the
      switch. Together, these findings establish that white and opaque cells are
      programmed for differential integration of metabolic and thermal cues and that
      opaque cells represent a more metabolically specialized cell state than the
      default white state. IMPORTANCE: Epigenetic transitions are an important
      mechanism by which microbes adapt to external stimuli. For Candida albicans, such
      transitions are crucial for adaptation to complex, fluctuating environments, and
      therefore contribute to its success as a human pathogen. The white-opaque switch
      modulates multiple C. albicans attributes, from sexual competency to niche
      specificity. Here, we demonstrate that metabolic circuits are extensively rewired
      between white and opaque states, so that the two cell types exhibit optimal
      fitness under different nutritional conditions and at different temperatures. We
      thereby establish that epigenetic events can profoundly alter the metabolism of
      fungal cells. We also demonstrate that epigenetic switching regulates
      filamentation and biofilm formation, two phenotypes closely associated with
      pathogenesis. These experiments reveal that white cells, considered the most
      clinically relevant form of C. albicans, are a "general-purpose" state suited to
      many environments, whereas opaque cells appear to represent a more metabolically
      specialized form of the species.

PMID- 27879331
TI  - Brd4 Activates Early Viral Transcription upon Human Papillomavirus 18 Infection
      of Primary Keratinocytes.
AB  - : Human papillomaviruses (HPVs) replicate in the cutaneous and mucosal epithelia,
      and the infectious cycle is synchronous with the differentiation program of the
      host keratinocytes. The virus initially infects dividing cells in the lower
      layers of the epithelium, where it establishes a persistent infection. The viral
      genome is maintained as a low-copy-number, extrachromosomal element in these
      proliferating cells but switches to the late stage of the life cycle in
      differentiated cells. The cellular chromatin adaptor protein Brd4 is involved in
      several stages and processes of the viral life cycle. In concert with the viral
      transcriptional regulator E2, Brd4 can repress transcription from the early viral
      promoter. Brd4 and E2 form a complex with the viral genome that associates with
      host chromosomes to partition the viral genome in dividing cells; Brd4 also
      localizes to active sites of productive HPV DNA replication. However, because of
      the difficulties in producing HPV viral particles, the role of Brd4 in modulating
      viral transcription and replication at the initial stage of infection is unclear.
      In this study, we have used an HPV18 quasivirus-based genome delivery system to
      assess the role of Brd4 in the initial infectivity of primary human
      keratinocytes. We show that, upon infection of primary human keratinocytes with
      HPV18 quasivirus, Brd4 activates viral transcription and replication.
      Furthermore, this activation is independent of the functional interaction between
      Brd4 and the HPV18 E2 protein. IMPORTANCE: HPVs lack encapsidated proteins and so
      rely exquisitely on host cellular factors to initiate their gene expression
      programs in newly infected cells. Brd4 is an important cellular chromatin adaptor
      molecule that normally activates host transcription initiation and elongation. In
      this study, we further optimize and utilize a quasivirus infection system to show
      that Brd4 activates HPV18 transcription at early stages of infection. HPVs are
      important human pathogens causing a wide range of cutaneous and tumorigenic
      morbidities. Therefore, specifically targeting this protein could provide a new
      target of therapeutic prevention of establishment of HPV infections.

PMID- 27879332
TI  - Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell
      Populations against Tuberculosis.
AB  - : Mycobacterium bovis Bacille Calmette-Guerin (BCG) is the only licensed vaccine
      against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls
      for improved vaccination strategies. Mucosal BCG vaccination generates superior
      protection against TB in animal models; however, the mechanisms of protection
      remain elusive. Tissue-resident memory T (TRM) cells have been implicated in
      protective immune responses against viral infections, but the role of TRM cells
      following mycobacterial infection is unknown. Using a mouse model of TB, we
      compared protection and lung cellular infiltrates of parenteral and mucosal BCG
      vaccination. Adoptive transfer and gene expression analyses of lung airway cells
      were performed to determine the protective capacities and phenotypes of different
      memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal
      and intranasal BCG vaccination generated T effector memory and TRM cells in the
      lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these
      airway-resident memory T cells into naive mice mediated protection against TB.
      Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and
      regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical
      TRM features. Our data demonstrate a key role for mucosal vaccination-induced
      airway-resident T cells in the host defense against pulmonary TB. These results
      have direct implications for the design of refined vaccination strategies.
      IMPORTANCE: BCG remains the only licensed vaccine against TB. Parenterally
      administered BCG has variable efficacy against pulmonary TB, and thus, improved
      prevention strategies and a more refined understanding of correlates of vaccine
      protection are required. Induction of memory T cells has been shown to be
      essential for protective TB vaccines. Mimicking the natural infection route by
      mucosal vaccination has been known to generate superior protection against TB in
      animal models; however, the mechanisms of protection have remained elusive. Here
      we performed an in-depth analysis to dissect the immunological mechanisms
      associated with superior mucosal protection in the mouse model of TB. We found
      that mucosal, and not subcutaneous, BCG vaccination generates lung-resident
      memory T cell populations that confer protection against pulmonary TB. We
      establish a comprehensive phenotypic characterization of these populations,
      providing a framework for future vaccine development.

PMID- 27879333
TI  - The Genome-Wide Interaction Network of Nutrient Stress Genes in Escherichia coli.
AB  - : Conventional efforts to describe essential genes in bacteria have typically
      emphasized nutrient-rich growth conditions. Of note, however, are the set of
      genes that become essential when bacteria are grown under nutrient stress. For
      example, more than 100 genes become indispensable when the model bacterium
      Escherichia coli is grown on nutrient-limited media, and many of these nutrient
      stress genes have also been shown to be important for the growth of various
      bacterial pathogens in vivo To better understand the genetic network that
      underpins nutrient stress in E. coli, we performed a genome-scale cross of
      strains harboring deletions in some 82 nutrient stress genes with the entire E.
      coli gene deletion collection (Keio) to create 315,400 double deletion mutants.
      An analysis of the growth of the resulting strains on rich microbiological media
      revealed an average of 23 synthetic sick or lethal genetic interactions for each
      nutrient stress gene, suggesting that the network defining nutrient stress is
      surprisingly complex. A vast majority of these interactions involved genes of
      unknown function or genes of unrelated pathways. The most profound synthetic
      lethal interactions were between nutrient acquisition and biosynthesis. Further,
      the interaction map reveals remarkable metabolic robustness in E. coli through
      pathway redundancies. In all, the genetic interaction network provides a powerful
      tool to mine and identify missing links in nutrient synthesis and to further
      characterize genes of unknown function in E. coli Moreover, understanding of
      bacterial growth under nutrient stress could aid in the development of novel
      antibiotic discovery platforms. IMPORTANCE: With the rise of antibiotic drug
      resistance, there is an urgent need for new antibacterial drugs. Here, we studied
      a group of genes that are essential for the growth of Escherichia coli under
      nutrient limitation, culture conditions that arguably better represent nutrient
      availability during an infection than rich microbiological media. Indeed, many
      such nutrient stress genes are essential for infection in a variety of pathogens.
      Thus, the respective proteins represent a pool of potential new targets for
      antibacterial drugs that have been largely unexplored. We have created all
      possible double deletion mutants through a genetic cross of nutrient stress genes
      and the E. coli deletion collection. An analysis of the growth of the resulting
      clones on rich media revealed a robust, dense, and complex network for nutrient
      acquisition and biosynthesis. Importantly, our data reveal new genetic
      connections to guide innovative approaches for the development of new
      antibacterial compounds targeting bacteria under nutrient stress.

PMID- 27879334
TI  - Intrinsic Resistance of Burkholderia cepacia Complex to Benzalkonium Chloride.
AB  - : Pharmaceutical products that are contaminated with Burkholderia cepacia complex
      (BCC) bacteria may pose serious consequences to vulnerable patients.
      Benzyldimethylalkylammonium chloride (BZK) cationic surfactants are extensively
      used in medical applications and have been implicated in the coselection of
      antimicrobial resistance. The ability of BCC to degrade BZK,
      tetradecyldimethylbenzylammonium chloride (C14BDMA-Cl),
      dodecyldimethylbenzylammonium chloride (C12BDMA-Cl), decyldimethylbenzylammonium
      chloride (C10BDMA-Cl), hexyldimethylbenzylammonium chloride, and
      benzyltrimethylammonium chloride was determined by incubation in 1/10-diluted
      tryptic soy broth (TSB) to determine if BCC bacteria have the ability to survive
      and inactivate these disinfectants. With BZK, C14BDMA-Cl, and C12BDMA-Cl,
      inhibition of the growth of 20 BCC strains was observed in disinfectant solutions
      that ranged from 64 to 256 ug/ml. The efflux pump inhibitor carbonyl cyanide m
      chlorophenylhydrazone increased the sensitivity of bacteria to 64 ug/ml BZK. The
      20 BCC strains grew well in 1/10-diluted TSB medium with BZK, C12BDMA-Cl, and
      C10BDMA-Cl; they absorbed and degraded the compounds in 7 days. Formation of
      benzyldimethylamine and benzylmethylamine as the initial metabolites suggested
      that the cleavage of the C alkyl-N bond occurred as the first step of BZK
      degradation by BCC bacteria. Proteomic data confirmed the observed efflux
      activity and metabolic inactivation via biodegradation in terms of BZK resistance
      of BCC bacteria, which suggests that the two main resistance mechanisms are
      intrinsic and widespread. IMPORTANCE: Benzyldimethylalkylammonium chloride is
      commonly used as an antiseptic in the United States. Several recent microbial
      outbreaks were linked to antiseptics that were found to contain strains of the
      Burkholderia cepacia complex. Burkholderia species survived in antiseptics,
      possibly because of the degradation of antiseptic molecules or regulation of
      relevant gene expression. In this study, we assessed the efflux pump and the
      potential of B. cepacia complex bacteria to degrade benzyldimethylalkylammonium
      chloride and improved our understanding of the resistance mechanisms, by using
      proteomic and metabolic information. To our knowledge, this is the first
      systematic report of the intrinsic mechanisms of B. cepacia complex strain
      resistance to benzyldimethylalkylammonium chloride, based on the metabolic and
      proteomic evidence for efflux pumps and the complete biodegradation of
      benzyldimethylalkylammonium chloride.

PMID- 27879335
TI  - Catabolite and Oxygen Regulation of Enterohemorrhagic Escherichia coli Virulence.
AB  - : The biogeography of the gut is diverse in its longitudinal axis, as well as
      within specific microenvironments. Differential oxygenation and nutrient
      composition drive the membership of microbial communities in these habitats.
      Moreover, enteric pathogens can orchestrate further modifications to gain a
      competitive advantage toward host colonization. These pathogens are versatile and
      adept when exploiting the human colon. They expertly navigate complex
      environmental cues and interkingdom signaling to colonize and infect their hosts.
      Here we demonstrate how enterohemorrhagic Escherichia coli (EHEC) uses three
      sugar-sensing transcription factors, Cra, KdpE, and FusR, to exquisitely regulate
      the expression of virulence factors associated with its type III secretion system
      (T3SS) when exposed to various oxygen concentrations. We also explored the effect
      of mucin-derived nonpreferred carbon sources on EHEC growth and expression of
      virulence genes. Taken together, the results show that EHEC represses the
      expression of its T3SS when oxygen is absent, mimicking the largely anaerobic
      lumen, and activates its T3SS when oxygen is available through Cra. In addition,
      when EHEC senses mucin-derived sugars heavily present in the O-linked and N
      linked glycans of the large intestine, virulence gene expression is initiated.
      Sugars derived from pectin, a complex plant polysaccharide digested in the large
      intestine, also increased virulence gene expression. Not only does EHEC sense
      host- and microbiota-derived interkingdom signals, it also uses oxygen
      availability and mucin-derived sugars liberated by the microbiota to stimulate
      expression of the T3SS. This precision in gene regulation allows EHEC to be an
      efficient pathogen with an extremely low infectious dose. IMPORTANCE: Enteric
      pathogens have to be crafty when interpreting multiple environmental cues to
      successfully establish themselves within complex and diverse gut
      microenvironments. Differences in oxygen tension and nutrient composition
      determine the biogeography of the gut microbiota and provide unique niches that
      can be exploited by enteric pathogens. EHEC is an enteric pathogen that colonizes
      the colon and causes outbreaks of bloody diarrhea and hemolytic-uremic syndrome
      worldwide. It has a very low infectious dose, which requires it to be an
      extremely effective pathogen. Hence, here we show that EHEC senses multiple sugar
      sources and oxygen levels to optimally control the expression of its virulence
      repertoire. This exquisite regulatory control equips EHEC to sense different
      intestinal compartments to colonize the host.

PMID- 27879337
TI  - Interactions between Melanin Enzymes and Their Atypical Recruitment to the
      Secretory Pathway by Palmitoylation.
AB  - : Melanins are biopolymers that confer coloration and protection to the host
      organism against biotic or abiotic insults. The level of protection offered by
      melanin depends on its biosynthesis and its subcellular localization. Previously,
      we discovered that Aspergillus fumigatus compartmentalizes melanization in
      endosomes by recruiting all melanin enzymes to the secretory pathway.
      Surprisingly, although two laccases involved in the late steps of melanization
      are conventional secretory proteins, the four enzymes involved in the early steps
      of melanization lack a signal peptide or a transmembrane domain and are thus
      considered "atypical" secretory proteins. In this work, we found interactions
      among melanin enzymes and all melanin enzymes formed protein complexes.
      Surprisingly, the formation of protein complexes by melanin enzymes was not
      critical for their trafficking to the endosomal system. By palmitoylation
      profiling and biochemical analyses, we discovered that all four early melanin
      enzymes were strongly palmitoylated during conidiation. However, only the
      polyketide synthase (PKS) Alb1 was strongly palmitoylated during both vegetative
      hyphal growth and conidiation when constitutively expressed alone. This
      posttranslational lipid modification correlates the endosomal localization of all
      early melanin enzymes. Intriguingly, bioinformatic analyses predict that
      palmitoylation is a common mechanism for potential membrane association of
      polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) in A.
      fumigatus Our findings indicate that protein-protein interactions facilitate
      melanization by metabolic channeling, while posttranslational lipid modifications
      help recruit the atypical enzymes to the secretory pathway, which is critical for
      compartmentalization of secondary metabolism. IMPORTANCE: Subcellular
      compartmentalization is increasingly recognized as an important aspect of fungal
      secondary metabolism. It facilitates sequential enzymatic reactions, provides
      mobility for enzymes and metabolites, and offers protection against self
      toxification. However, how compartmentalization is achieved remains unclear given
      that the majority of enzymes encoded by secondary metabolism gene clusters are
      predicted to be cytosolic proteins. Through studying melanization in Aspergillus,
      we previously found that all enzymes involved in the early steps of melanization
      are atypical secretory proteins. Here, we discovered physical interactions among
      melanin enzymes. However, it was the posttranslational palmitoylation rather than
      the physical interaction that was responsible for their recruitment to the
      secretory pathway. Intriguingly, palmitoylation is likely a common mechanism for
      potential membrane association of polyketide synthases (PKSs) and nonribosomal
      peptide synthetases (NRPSs) in A. fumigatus Collectively, our findings suggest
      that posttranslational lipid modification helps direct secondary metabolism to
      defined organelles for biosynthesis and trafficking.

PMID- 27879336
TI  - Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux
      Pump in Salmonella Biology.
AB  - : For over 20 years, bacterial multidrug resistance (MDR) efflux pumps have been
      studied because of their impact on resistance to antimicrobials. However,
      critical questions remain, including why produce efflux pumps under non
      antimicrobial treatment conditions, and why have multiple pumps if their only
      purpose is antimicrobial efflux? Salmonella spp. possess five efflux pump
      families, including the resistance-nodulation-division (RND) efflux pumps.
      Notably, the RND efflux pump AcrD has a unique substrate profile, distinct from
      other Salmonella efflux pumps. Here we show that inactivation of acrD results in
      a profoundly altered transcriptome and modulation of pathways integral to
      Salmonella biology. The most significant transcriptome changes were central
      metabolism related, with additional changes observed in pathogenicity,
      environmental sensing, and stress response pathway expression. The extent of
      tricarboxylic acid cycle and fumarate metabolism expression changes led us to
      hypothesize that acrD inactivation may result in motility defects due to
      perturbation of metabolite concentrations, such as fumarate, for which a role in
      motility has been established. Despite minimal detectable changes in flagellar
      gene expression, we found that an acrD mutant Salmonella enterica serovar
      Typhimurium isolate was significantly impaired for swarming motility, which was
      restored by addition of fumarate. The acrD mutant outcompeted the wild type in
      fitness experiments. The results of these diverse experiments provide strong
      evidence that the AcrD efflux pump is not simply a redundant system providing
      response resilience, but also has distinct physiological functions. Together,
      these data indicate that the AcrD efflux pump has a significant and previously
      underappreciated impact on bacterial biology, despite only minor perturbations of
      antibiotic resistance profiles. IMPORTANCE: Efflux pumps in Gram-negative
      bacteria are studied because of their important contributions to antimicrobial
      resistance. However, the role of these pumps in bacterial biology has remained
      surprisingly elusive. Here, we provide evidence that loss of the AcrD efflux pump
      significantly impacts the physiology of Salmonella enterica serovar Typhimurium.
      Inactivation of acrD led to changes in the expression of 403 genes involved in
      fundamental processes, including basic metabolism, virulence, and stress
      responses. Pathways such as these allow Salmonella to grow, survive in the
      environment, and cause disease. Indeed, our data show that the acrD mutant is
      more fit than wild-type Salmonella under standard lab conditions. We hypothesized
      that inactivation of acrD would alter levels of bacterial metabolites, impacting
      traits such as swarming motility. We demonstrated this by exogenous addition of
      the metabolite fumarate, which partially restored the acrD mutant's swarming
      defect. This work extends our understanding of the role of bacterial efflux
      pumps.

PMID- 27879339
TI  - MCT8 deficiency in Purkinje cells disrupts embryonic chicken cerebellar
      development.
AB  - Inactivating mutations in the human SLC16A2 gene encoding the thyroid hormone
      transporter monocarboxylate transporter 8 (MCT8) result in the Allan-Herndon
      Dudley syndrome accompanied by severe locomotor deficits. The underlying
      mechanisms of the associated cerebellar maldevelopment were studied using the
      chicken as a model. Electroporation of an MCT8-RNAi vector into the cerebellar
      anlage of a 3-day-old embryo allowed knockdown of MCT8 in Purkinje cell
      precursors. This resulted in the downregulation of the thyroid hormone-responsive
      gene RORalpha and the Purkinje cell-specific differentiation marker LHX1/5 at day
      6. MCT8 knockdown also results in a smaller and less complex dendritic tree at
      day 18 suggesting a pivotal role of MCT8 for cell-autonomous Purkinje cell
      maturation. Early administration of the thyroid hormone analogue 3,5,3'
      triiodothyroacetic acid partially rescued early Purkinje cell differentiation.
      MCT8-deficient Purkinje cells also induced non-autonomous effects as they led to
      a reduced granule cell precursor proliferation, a thinner external germinal layer
      and a loss of PAX6 expression. By contrast, at day 18, the external germinal
      layer thickness was increased, with an increase in presence of Axonin-1-positive
      post-mitotic granule cells in the initial stage of radial migration. The
      concomitant accumulation of presumptive migrating granule cells in the molecular
      layer, suggests that inward radial migration to the internal granular layer is
      stalled. In conclusion, early MCT8 deficiency in Purkinje cells results in both
      cell-autonomous and non-autonomous effects on cerebellar development and
      indicates that MCT8 expression is essential from very early stages of
      development, providing a novel insight into the ontogenesis of the Allan-Herndon
      Dudley syndrome.

PMID- 27879338
TI  - Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface
      Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and
      Ebolavirus Glycoproteins.
AB  - : Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition
      to the canonical Gag, Pol, and Env proteins that will form progeny virus
      particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains
      the entire Gag sequence plus an 88-residue N-terminal extension. It has recently
      been reported that glycogag, like the Nef protein of HIV-1, counteracts the
      antiviral effects of the cellular protein Serinc5. We have found, in agreement
      with prior work, that glycogag strongly enhances the infectivity of MLVs with
      some Env proteins but not those with others. In contrast, however, glycogag was
      detrimental to MLVs carrying Ebolavirus glycoprotein. Glycogag could be replaced,
      with respect to viral infectivity, by the unrelated S2 protein of equine
      infectious anemia virus. We devised an assay for viral entry in which virus
      particles deliver the Cre recombinase into cells, leading to the expression of a
      reporter. Data from this assay showed that both the positive and the negative
      effects of glycogag and S2 upon MLV infectivity are exerted at the level of virus
      entry. Moreover, transfection of the virus-producing cells with a Serinc5
      expression plasmid reduced the infectivity and entry capability of MLV carrying
      xenotropic MLV Env, particularly in the absence of glycogag. Conversely, Serinc5
      expression abrogated the negative effects of glycogag upon the infectivity and
      entry capability of MLV carrying Ebolavirus glycoprotein. As Serinc5 may
      influence cellular phospholipid metabolism, it seems possible that all of these
      effects on virus entry derive from changes in the lipid composition of viral
      membranes. IMPORTANCE: Many murine leukemia viruses (MLVs) encode a protein
      called "glycogag." The function of glycogag is not fully understood, but it can
      assist HIV-1 replication in the absence of the HIV-1 protein Nef under some
      circumstances. In turn, Nef counteracts the cellular protein Serinc5. Glycogag
      enhances the infectivity of MLVs with some but not all MLV Env proteins (which
      mediate viral entry into the host cell upon binding to cell surface receptors).
      We now report that glycogag acts by enhancing viral entry and that, like Nef,
      glycogag antagonizes Serinc5. Surprisingly, the effects of glycogag and Serinc5
      upon the entry and infectivity of MLV particles carrying an Ebolavirus
      glycoprotein are the opposite of those observed with the MLV Env proteins. The
      unrelated S2 protein of equine infectious anemia virus (EIAV) is functionally
      analogous to glycogag in our experiments. Thus, three retroviruses (HIV-1, MLV,
      and EIAV) have independently evolved accessory proteins that counteract Serinc5.

PMID- 27879340
TI  - G Protein-Coupled Receptor Endocytosis Confers Uniformity in Responses to
      Chemically Distinct Ligands.
AB  - The ability of chemically distinct ligands to produce different effects on the
      same G protein-coupled receptor (GPCR) has interesting therapeutic implications,
      but, if excessively propagated downstream, would introduce biologic noise
      compromising cognate ligand detection. We asked whether cells have the ability to
      limit the degree to which chemical diversity imposed at the ligand-GPCR interface
      is propagated to the downstream signal. We carried out an unbiased analysis of
      the integrated cellular response elicited by two chemically and
      pharmacodynamically diverse beta-adrenoceptor agonists, isoproterenol and
      salmeterol. We show that both ligands generate an identical integrated response,
      and that this stereotyped output requires endocytosis. We further demonstrate
      that the endosomal beta2-adrenergic receptor signal confers uniformity on the
      downstream response because it is highly sensitive and saturable. Based on these
      findings, we propose that GPCR signaling from endosomes functions as a biologic
      noise filter to enhance reliability of cognate ligand detection.

PMID- 27879341
TI  - Dynamin Functions and Ligands: Classical Mechanisms Behind.
AB  - Dynamin is a GTPase that plays a vital role in clathrin-dependent endocytosis and
      other vesicular trafficking processes by acting as a pair of molecular scissors
      for newly formed vesicles originating from the plasma membrane. Dynamins and
      related proteins are important components for the cleavage of clathrin-coated
      vesicles, phagosomes, and mitochondria. These proteins help in organelle
      division, viral resistance, and mitochondrial fusion/fission. Dysfunction and
      mutations in dynamin have been implicated in the pathophysiology of various
      disorders, such as Alzheimer's disease, Parkinson's disease, Huntington's
      disease, Charcot-Marie-Tooth disease, heart failure, schizophrenia, epilepsy,
      cancer, dominant optic atrophy, osteoporosis, and Down's syndrome. This review is
      an attempt to illustrate the dynamin-related mechanisms involved in the above
      mentioned disorders and to help medicinal chemists to design novel dynamin
      ligands, which could be useful in the treatment of dynamin-related disorders.

PMID- 27879342
TI  - Tenacious assumptions of person-centred care? Exploring tensions and variations
      in practice.
AB  - In recent decades, the 'tenacious assumptions' of biomedicine regarding the
      neutrality and universality of its knowledge claims have been significantly
      challenged by the growth of new collaborative and patient-focused models of
      Healthcare delivery. In this article, we discuss and critically reflect upon one
      such alternative Healthcare model developed at the University of Gothenburg
      Centre for Person-Centred Care in Sweden. This centre uses three clinical
      routines of narrative, partnership and documentation to provide Healthcare to
      people recognized as unique individuals rather than patients. Person-centred care
      in Gothenburg and more broadly is based on the assumption that a person is
      independently capable of reasoning and verbal expression and willing to provide
      clear and genuine narratives and cooperate with Healthcare professionals.
      However, we argue that by emphasizing individual capabilities of reasoning and
      verbal expression, an unnecessarily limited conception of personhood risks being
      imposed on these routines. Drawing upon semi-structured interviews with
      researchers in three very different Gothenburg Centre for Person-Centred Care
      research projects - about healthy ageing in migrant communities, neurogenic
      communication disorders, and psychosis - we highlight that how persons are
      recognized as unique and capable varies significantly in practice across
      different Healthcare settings. Thus, we assert that person-centred care's own
      potentially tenacious assumptions about the attributes of personhood risk
      distracting attention away from the variety of creative ways that professionals
      and persons promisingly find for translating the ideal of person-centred care
      into practice.

PMID- 27879343
TI  - Serine threonine kinase receptor associated protein regulates early follicle
      development in the mouse ovary.
AB  - The molecular mechanisms involved in regulating the development of small,
      gonadotrophin-independent follicles are poorly understood; however, many studies
      have highlighted an essential role for TGFB ligands. Canonical TGFB signalling is
      dependent upon intracellular SMAD proteins that regulate transcription. STRAP has
      been identified in other tissues as an inhibitor of the TGFB-SMAD signalling
      pathway. Therefore, in this study we aimed to determine the expression and role
      of STRAP in the context of early follicle development. Using qPCR, Strap, Smad3
      and Smad7 revealed similar expression profiles in immature ovaries from mice aged
      4-16 days containing different populations of early growing follicles. STRAP and
      SMAD2/3 proteins co-localised in granulosa cells of small follicles using
      immunofluorescence. Using an established culture model, neonatal mouse ovary
      fragments with a high density of small non-growing follicles were used to examine
      the effects of Strap knockdown using siRNA and STRAP protein inhibition by immuno
      neutralisation. Both interventions caused a reduction in the proportion of small,
      non-growing follicles and an increase in the proportion and size of growing
      follicles in comparison to untreated controls, suggesting inhibition of STRAP
      facilitates follicle activation. Recombinant STRAP protein had no effect on
      small, non-growing follicles, but increased the mean oocyte size of growing
      follicles in the neonatal ovary model and also promoted the growth of isolated
      preantral follicles in vitro Overall findings indicate STRAP is expressed in the
      mouse ovary and is capable of regulating development of small follicles in a
      stage-dependent manner.

PMID- 27879344
TI  - Failure to launch: aberrant cumulus gene expression during oocyte in vitro
      maturation.
AB  - In vitro maturation (IVM) offers significant benefits for human infertility
      treatment and animal breeding, but this potential is yet to be fully realised due
      to reduced oocyte developmental competence in comparison with in vivo matured
      oocytes. Cumulus cells occupy an essential position in determining oocyte
      developmental competence. Here we have examined the areas of deficient gene
      expression, as determined within microarrays primarily from cumulus cells of
      mouse COCs, but also other species, between in vivo matured and in vitro matured
      oocytes. By retrospectively analysing the literature, directed by focussing on
      downregulated genes, we provide an insight as to why the in vitro cumulus cells
      fail to support full oocyte potential and dissect molecular pathways that have
      important roles in oocyte competence. We conclude that the roles of epidermal
      growth factor signalling, the expanded extracellular matrix, cumulus cell
      metabolism and the immune system are critical deficiencies in cumulus cells of
      IVM COCs.

PMID- 27879345
TI  - The role of lymph node size and FOXP3+ regulatory T cells in node-negative colon
      cancer.
AB  - Recently, we demonstrated that the intratumoural density of CD3+ and CD8+ T cells
      is independently prognostic and associated with lymph node (LN) harvest and LN
      size in node-negative colon cancer. We assumed that FOXP3+ T cells (Tregs) could
      be inversely associated with these LN features. Therefore, we performed a
      retrospective immunohistochemical analysis using an already well-characterised
      collection of stage I/II colon cancer cases. Receiver operating characteristic
      analysis revealed the optimal cut-off for predicting cancer-related death to be
      70 FOXP3+ Tregs/mm2 at the invasion front. Other than T-stage, none of the
      relevant histopathological parameters were associated with the density of FOXP3+
      cells. In particular, no relation to LN size and count were found. Cancer
      specific survival was significantly improved in cases with high densities (115 vs
      86 months; p=0.026) in univariable but not in multivariable analysis. In contrast
      to other cancers, FOXP3+ T cells are associated with a favourable outcome.

PMID- 27879346
TI  - A Zebrafish Model for a Human Myopathy Associated with Mutation of the
      Unconventional Myosin MYO18B.
AB  - Myosin 18B is an unconventional myosin that has been implicated in tumor
      progression in humans. In addition, loss-of-function mutations of the MYO18B gene
      have recently been identified in several patients exhibiting symptoms of nemaline
      myopathy. In mouse, mutation of Myo18B results in early developmental arrest
      associated with cardiomyopathy, precluding analysis of its effects on skeletal
      muscle development. The zebrafish, frozen (fro) mutant was identified as one of a
      group of immotile mutants in the 1996 Tubingen genetic screen. Mutant embryos
      display a loss of birefringency in their skeletal muscle, indicative of disrupted
      sarcomeric organization. Using meiotic mapping, we localized the fro locus to the
      previously unannotated zebrafish myo18b gene, the product of which shares close
      to 50% identity with its human ortholog. Transcription of myo18b is restricted to
      fast-twitch myocytes in the zebrafish embryo; consistent with this, fro mutant
      embryos exhibit defects specifically in their fast-twitch skeletal muscles. We
      show that sarcomeric assembly is blocked at an early stage in fro mutants,
      leading to the disorganized accumulation of actin, myosin, and alpha-actinin and
      a complete loss of myofibrillar organization in fast-twitch muscles.

PMID- 27879347
TI  - Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related
      Macular Degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in
      ageing societies, triggered by both environmental and genetic factors. The
      strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele
      was found previously over a chromosomal region in 10q26 harboring two genes,
      ARMS2 and HTRA1, although with little knowledge as to which gene or genetic
      variation is functionally relevant to AMD pathology. In this study, we analyzed
      rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the
      International AMD Genomics Consortium and identified variants in ARMS2 but not
      HTRA1 to exclusively carry the AMD risk with P-values between 1.0 * 10-773 and
      6.7 * 10-5 This now allows prioritization of the gene of interest for subsequent
      functional studies.

PMID- 27879348
TI  - The Effects of Migration and Assortative Mating on Admixture Linkage
      Disequilibrium.
AB  - Statistical models in medical and population genetics typically assume that
      individuals assort randomly in a population. While this simplifies model
      complexity, it contradicts an increasing body of evidence of nonrandom mating in
      human populations. Specifically, it has been shown that assortative mating is
      significantly affected by genomic ancestry. In this work, we examine the effects
      of ancestry-assortative mating on the linkage disequilibrium between local
      ancestry tracks of individuals in an admixed population. To accomplish this, we
      develop an extension to the Wright-Fisher model that allows for ancestry-based
      assortative mating. We show that ancestry-assortment perturbs the distribution of
      local ancestry linkage disequilibrium (LAD) and the variance of ancestry in a
      population as a function of the number of generations since admixture. This
      assortment effect can induce errors in demographic inference of admixed
      populations when methods assume random mating. We derive closed form formulae for
      LAD under an assortative-mating model with and without migration. We observe that
      LAD depends on the correlation of global ancestry of couples in each generation,
      the migration rate of each of the ancestral populations, the initial proportions
      of ancestral populations, and the number of generations since admixture. We also
      present the first direct evidence of ancestry-assortment in African Americans and
      examine LAD in simulated and real admixed population data of African Americans.
      We find that demographic inference under the assumption of random mating
      significantly underestimates the number of generations since admixture, and that
      accounting for assortative mating using the patterns of LAD results in estimates
      that more closely agrees with the historical narrative.

PMID- 27879350
TI  - Response to: 'Carpal tunnel syndrome and its relationship with occupation and
      sex: from objective evaluation to patients' care' by Coraci et al.

PMID- 27879351
TI  - Carpal tunnel syndrome and its relationship with occupation and sex: from
      objective evaluation to patients' care.

PMID- 27879353
TI  - 2016 Health Care & Education Presidential Address: If DSME Were a Pill, Would You
      Prescribe It?
AB  - This address was delivered by Margaret A. Powers, PhD, RD, CDE, President, Health
      Care & Education, of the American Diabetes Association (ADA), at the ADA's 76th
      Scientific Sessions in New Orleans, LA, on 11 June 2016. Dr. Powers conducts
      research and has a clinical practice as a registered dietitian and diabetes
      educator at the International Diabetes Center at Park Nicollet in Minneapolis.
      Her research focuses on improving diabetes outcomes including factors that affect
      the clinical, psychosocial, and behavioral aspects of diabetes. Dr. Powers has
      been an ADA volunteer for more than 25 years, including serving as a founding
      editor of Diabetes Spectrum She is the lead author of the 2015 joint Position
      Statement on Diabetes Self-management Education and Support published by the ADA,
      American Association of Diabetes Educators, and Academy of Nutrition and
      Dietetics. She is the recipient of the ADA's Outstanding Educator in Diabetes
      Award and has published research, authored numerous articles and chapters,
      published five books, and is an international presenter. Dr. Powers holds a
      doctorate in education with a focus on performance improvement from Capella
      University. She received her Master of Science from the University of Illinois at
      Chicago and her Bachelor of Science from Michigan State University. She completed
      her dietetic internship at Cook County Hospital in Chicago.

PMID- 27879356
TI  - Harold E. Lebovitz, MD: Legendary Diabetologist.

PMID- 27879349
TI  - NCAM1 Polysialylation: The Prion Protein's Elusive Reason for Being?
AB  - Much confusion surrounds the physiological function of the cellular prion protein
      (PrPC). It is, however, anticipated that knowledge of its function will shed
      light on its contribution to neurodegenerative diseases and suggest ways to
      interfere with the cellular toxicity central to them. Consequently, efforts to
      elucidate its function have been all but exhaustive. Building on earlier work
      that uncovered the evolutionary descent of the prion founder gene from an
      ancestral ZIP zinc transporter, we recently investigated a possible role of PrPC
      in a morphogenetic program referred to as epithelial-to-mesenchymal transition
      (EMT). By capitalizing on PrPC knockout cell clones in a mammalian cell model of
      EMT and using a comparative proteomics discovery strategy, neural cell adhesion
      molecule-1 emerged as a protein whose upregulation during EMT was perturbed in
      PrPC knockout cells. Follow-up work led us to observe that PrPC regulates the
      polysialylation of the neural cell adhesion molecule NCAM1 in cells undergoing
      morphogenetic reprogramming. In addition to governing cellular migration,
      polysialylation modulates several other cellular plasticity programs PrPC has
      been phenotypically linked to. These include neurogenesis in the subventricular
      zone, controlled mossy fiber sprouting and trimming in the hippocampal formation,
      hematopoietic stem cell renewal, myelin repair and maintenance, integrity of the
      circadian rhythm, and glutamatergic signaling. This review revisits this body of
      literature and attempts to present it in light of this novel contextual
      framework. When approached in this manner, a coherent model of PrPC acting as a
      regulator of polysialylation during specific cell and tissue morphogenesis events
      comes into focus.

PMID- 27879354
TI  - Ablation of the Duodenal Mucosa as a Strategy for Glycemic Control in Type 2
      Diabetes: Role of Nutrient Signaling or Simple Weight Loss.

PMID- 27879355
TI  - Pregnancy Outcomes in Women With Diabetes-Lessons Learned From Clinical Research:
      The 2015 Norbert Freinkel Award Lecture.
AB  - Among women with diabetes, the worst pregnancy outcome is seen in the subgroup of
      women with diabetic nephropathy. Development of severe preeclampsia that leads to
      early preterm delivery is frequent. Predictors and pathophysiological mechanisms
      for the development of preeclampsia among women with diabetes and observational
      studies that support antihypertension treatment for pregnant women with
      microalbuminuria or diabetic nephropathy preventing preeclampsia and early
      preterm delivery are presented here. Obtaining and maintaining strict glycemic
      control before and during pregnancy is paramount to prevent preterm delivery. The
      cornerstones of diabetes management are appropriate diet and insulin, although
      the risk of severe hypoglycemia always needs to be taken into account when
      tailoring a diabetes treatment plan. Pathophysiological mechanisms of the
      increased risk of hypoglycemia during pregnancy are explored, and studies
      evaluating the use of insulin analogs, insulin pumps, and continuous glucose
      monitoring to improve pregnancy outcomes and to reduce the risk of severe
      hypoglycemia in pregnant women with type 1 diabetes are reported. In addition to
      strict glycemic control, other factors involved in fetal overgrowth are explored,
      and restricting maternal gestational weight gain is a promising treatment area.
      The optimal carbohydrate content of the diet is discussed. In summary, the
      lessons learned from this clinical research are that glycemic control,
      gestational weight gain, and antihypertension treatment all are of importance for
      improving pregnancy outcomes in pregnant women with preexisting diabetes. An
      example of how to use app technology to share the recent evidence-based clinical
      recommendations for women with diabetes who are pregnant or planning pregnancy is
      given.

PMID- 27879357
TI  - Psychosocial Research and Care in Diabetes: Altering Lives by Understanding
      Attitudes.

PMID- 27879361
TI  - Comment on Crews et al. Role and Determinants of Adherence to Off-loading in
      Diabetic Foot Ulcer Healing: A Prospective Investigation. Diabetes Care
      2016;39:1371-1377.

PMID- 27879358
TI  - Psychosocial Care for People With Diabetes: A Position Statement of the American
      Diabetes Association.

PMID- 27879359
TI  - Effect of DECIDE (Decision-making Education for Choices In Diabetes Everyday)
      Program Delivery Modalities on Clinical and Behavioral Outcomes in Urban African
      Americans With Type 2 Diabetes: A Randomized Trial.
AB  - OBJECTIVE: To compare the effectiveness of three delivery modalities of Decision
      making Education for Choices In Diabetes Everyday (DECIDE), a nine-module,
      literacy-adapted diabetes and cardiovascular disease (CVD) education and problem
      solving training, compared with an enhanced usual care (UC), on clinical and
      behavioral outcomes among urban African Americans with type 2 diabetes. RESEARCH
      DESIGN AND METHODS: Eligible participants (n = 182) had a suboptimal CVD risk
      factor profile (A1C, blood pressure, and/or lipids). Participants were randomized
      to DECIDE Self-Study (n = 46), DECIDE Individual (n = 45), DECIDE Group (n = 46),
      or Enhanced UC (n = 45). Intervention duration was 18-20 weeks. Outcomes were
      A1C, blood pressure, lipids, problem-solving, disease knowledge, and self-care
      activities, all measured at baseline, 1 week, and 6 months after completion of
      the intervention. RESULTS: DECIDE modalities and Enhanced UC did not
      significantly differ in clinical outcomes at 6 months postintervention. In
      participants with A1C >=7.5% (58 mmol/mol) at baseline, A1C declined in each
      DECIDE modality at 1 week postintervention (P < 0.05) and only in Self-Study at 6
      months postintervention (b = -0.24, P < 0.05). There was significant reduction in
      systolic blood pressure in Self-Study (b = -4.04) and Group (b = -3.59) at 6
      months postintervention. Self-Study, Individual, and Enhanced UC had significant
      declines in LDL and Self-Study had an increase in HDL (b = 1.76, P < 0.05) at 6
      months postintervention. Self-Study and Individual had a higher increase in
      knowledge than Enhanced UC (P < 0.05), and all arms improved in problem-solving
      (P < 0.01) at 6 months postintervention. CONCLUSIONS: DECIDE modalities showed
      benefits after intervention. Self-Study demonstrated robust improvements across
      clinical and behavioral outcomes, suggesting program suitability for broader
      dissemination to populations with similar educational and literacy levels.

PMID- 27879362
TI  - Response to Comment on Crews et al. Role and Determinants of Adherence to Off
      loading in Diabetic Foot Ulcer Healing: A Prospective Investigation. Diabetes
      Care 2016;39:1371-1377.

PMID- 27879363
TI  - Comment on Ferrannini et al. CV Protection in the EMPA-REG OUTCOME Trial: A
      "Thrifty Substrate" Hypothesis. Diabetes Care 2016;39:1108-1114.

PMID- 27879364
TI  - Response to Comment on Ferrannini et al. CV Protection in the EMPA-REG OUTCOME
      Trial: A "Thrifty Substrate" Hypothesis. Diabetes Care 2016;39:1108-1114.

PMID- 27879365
TI  - Comment on Shahraz et al. Do Patient Characteristics Impact Decisions by
      Clinicians on Hemoglobin A1c Targets? Diabetes Care 2016;38:e145-e146.

PMID- 27879366
TI  - Response to Comment on Shahraz et al. Do Patient Characteristics Impact Decisions
      by Clinicians on Hemoglobin A1c Targets? Diabetes Care 2016;38: e145-e146.

PMID- 27879368
TI  - 99mTc-Duramycin SPECT Imaging of Early Tumor Response to Targeted Therapy: A
      Comparison with 18F-FDG PET.
AB  - Molecular imaging of cell death may provide a detailed readout of the cellular
      response to novel therapies and prognostic information on tumor treatment
      efficacy, assisting in the design of individualized therapy. We compared the
      predictive power of cell death imaging using 99mTc-duramycin with the current
      gold standard 18F-FDG for treatment response evaluation after targeted therapy.
      Methods: Early therapy response evaluation was assessed by 99mTc-duramycin SPECT
      and 18F-FDG PET imaging in treatment-sensitive COLO205 and treatment-resistant
      HT29 human colorectal cancer xenografts 24 h after a single dose of conatumumab
      or IgG1 control. The specificity of 99mTc-duramycin for apoptosis was assessed
      using 99mTc-linear duramycin control radiotracer. Radiotracer uptake was
      validated ex vivo by gamma-counting and autoradiography and compared with cleaved
      caspase-3 (CC3) activation and DNA fragmentation (TdT-mediated dUTP nick-end
      labeling [TUNEL]). Data were analyzed with the Student t test and Pearson
      correlation. All statistical tests were 2-sided. Results: COLO205 tumor uptake of
      99mTc-duramycin was increased 7-fold from baseline in conatumumab- versus IgG1
      treated control mice (P < 0.001), in good correlation with histologic analysis of
      apoptosis (CC3, r = 0.842, and TUNEL, r = 0.894; P < 0.001). No response was
      detected in HT29 tumors. No change in 99mTc-linear duramycin uptake could be
      detected in COLO205 tumors after treatment, indicating specificity of the 99mTc
      duramycin tumor signal. 18F-FDG uptake was not significantly increased from
      baseline in conatumumab- versus IgG1-treated COLO205 and HT29 tumor-bearing mice
      (P = 0.104 and 0.779, respectively) and did not correlate with
      immunohistochemical evidence of apoptosis. Conclusion: We have demonstrated that
      99mTc-duramycin specifically accumulates in apoptotic tumors in which 18F-FDG was
      not able to differentiate responding from nonresponding tumors early after
      treatment. 99mTc-duramycin holds promise as a noninvasive imaging radiotracer for
      early treatment evaluation in the clinic.

PMID- 27879369
TI  - Response Assessment Criteria and Their Applications in Lymphoma: Part 2.
AB  - Interim and end-of-treatment PET/CT have become central to the evaluation of
      Hodgkin and non-Hodgkin lymphoma. This review article seeks to aid clinical
      decision making by providing an overview of available data on the diagnostic and
      prognostic value of PET/CT imaging for response assessment and pretransplant
      evaluation in lymphoma. The relative strengths and limitations of these
      techniques in various disease subtypes and clinical scenarios are explored, along
      with their current standards for reporting and latest developments. Particular
      attention is given to response-adapted therapy, which is emerging as a
      cornerstone of clinical management.

PMID- 27879370
TI  - Validation of MRI Determination of the Penumbra by PET Measurements in Ischemic
      Stroke.
AB  - The concept of the ischemic penumbra was formulated on the basis of animal
      experiments showing functional impairment and electrophysiologic disturbances
      with decreasing flow to the brain below defined values (the threshold for
      function) and irreversible tissue damage with blood supply further decreased (the
      threshold for infarction). The perfusion range between these thresholds was
      termed the "penumbra," and restitution of flow above the functional threshold was
      able to reverse the deficits without permanent damage. In further experiments,
      the dependency of the development of irreversible lesions on the interaction of
      the severity and the duration of critically reduced blood flow was established,
      proving that the lower the flow, the shorter the time for efficient reperfusion.
      As a consequence, infarction develops from the core of ischemia to the areas of
      less severe hypoperfusion. The translation of this experimental concept as the
      basis for the efficient treatment of stroke requires noninvasive methods with
      which regional flow and energy metabolism can be repeatedly investigated to
      demonstrate penumbra tissue, which can benefit from therapeutic interventions.
      PET allows the quantification of regional cerebral blood flow, the regional
      oxygen extraction fraction, and the regional metabolic rate for oxygen. With
      these variables, clear definitions of irreversible tissue damage and of
      critically hypoperfused but potentially salvageable tissue (i.e., the penumbra)
      in stroke patients can be achieved. However, PET is a research tool, and its
      complex logistics limit clinical routine applications. Perfusion-weighted or
      diffusion-weighted MRI is a widely applicable clinical tool, and the "mismatch"
      between perfusion-weighted and diffusion-weighted abnormalities serves as an
      indicator of the penumbra. However, comparative studies of perfusion-weighted or
      diffusion-weighted MRI and PET have indicated overestimation of the core of
      irreversible infarction as well as of the penumbra by the MRI modalities. Some of
      these discrepancies can be explained by the nonselective application of relative
      perfusion thresholds, which might be improved by more complex analytic
      procedures. The heterogeneity of the MRI signatures used for the definition of
      the mismatch are also responsible for disappointing results in the application of
      perfusion-weighted or diffusion-weighted MRI to the selection of patients for
      clinical trials. As long as validation of the mismatch selection paradigm is
      lacking, the use of this paradigm as a surrogate marker of outcome is limited.

PMID- 27879367
TI  - Alternative Splicing of EZH2 pre-mRNA by SF3B3 Contributes to the Tumorigenic
      Potential of Renal Cancer.
AB  - Purpose: Deregulation or mutation of the EZH2 gene causes various tumors,
      including clear cell renal cell carcinoma (ccRCC). Although several splice
      variants of EZH2 have been identified, little is known about how EZH2 splicing is
      regulated or the contribution of alternative splicing to its protumorigenic
      functions.Experimental Design: We conducted RT-PCR, Western blot analysis, and
      IHC techniques to examine EZH2 and its alternative splicing transcript expression
      in renal cancer tissue and renal cancer cell lines. Proliferation, migration,
      clonogenicity, and tumorigenicity of renal cancer cells either exhibiting
      knockdown of EZH2 or its splicing factor SF3B3 were assessed by CCK8, Transwell
      assay, and murine xenograft experiments.Results: We found that the inclusion of
      alternative EZH2 exon 14 was significantly increased in ccRCC samples and renal
      cancer cell lines. In ccRCC lines, enforced expression of EZH2Delta14 inhibited,
      and EZH2 promoted, cell growth, migration, proliferation, and tumorigenicity in a
      xenograft model. Mechanistic studies demonstrated that EZH2Delta14 isoform
      functions as a dominant-negative inhibitor of full-length EZH2. Coexpression of
      EZH2Delta14 variant with full-length EZH2 not only abrogated DAB2IP and HOXA9
      suppression but also inhibited EZH2-driven tumorigenesis. Strikingly, the
      splicing factor SF3B3 stimulates inclusion of exon14 and has pro-proliferative
      activity. Importantly, the upregulation of SF3B3 expression observed in clinical
      ccRCC samples parallels the increased inclusion of EZH2 exon14, and the SF3B3
      level is associated with higher tumor stage and poor overall
      survival.Conclusions: These results suggest SF3B3 as a key regulator of EZH2 pre
      mRNA splicing and SF3B3 may represent a novel prognostic factor and potential
      therapeutic target in ccRCC. Clin Cancer Res; 23(13); 3428-41. (c)2016 AACR.

PMID- 27879371
TI  - Small Data: A Ubiquitous, Yet Untapped, Resource for Low-Cost Imaging Innovation.

PMID- 27879372
TI  - Metabolic Imaging in Parkinson Disease.
AB  - This review focuses on recent human 18F-FDG PET studies in Parkinson disease.
      First, an overview is given of the current analytic approaches to metabolic brain
      imaging data. Next, we discuss how 18F-FDG PET studies have advanced
      understanding of the relation between distinct brain regions and associated
      symptoms in Parkinson disease, including cognitive decline. In addition, the
      value of 18F-FDG PET studies in differential diagnosis, identifying prodromal
      patients, and the evaluation of treatment effects are reviewed. Finally,
      anticipated developments in the field are addressed.

PMID- 27879373
TI  - Novel "Add-On" Molecule Based on Evans Blue Confers Superior Pharmacokinetics and
      Transforms Drugs to Theranostic Agents.
AB  - One of the major design considerations for a drug is its pharmacokinetics in the
      blood. A drug with a short half-life in the blood is less available at a target
      organ. Such a limitation dictates treatment with either high doses or more
      frequent doses, both of which may increase the likelihood of undesirable side
      effects. To address the need for additional methods to improve the blood half
      life of drugs and molecular imaging agents, we developed an "add-on" molecule
      that contains 3 groups: a truncated Evans blue dye molecule that binds to albumin
      with a low micromolar affinity and provides a prolonged half-life in the blood; a
      metal chelate that allows radiolabeling for imaging and radiotherapy; and
      maleimide for easy conjugation to drug molecules. Methods: The truncated Evans
      blue molecule was conjugated with the chelator NOTA or DOTA, and the resulting
      conjugate was denoted as NMEB or DMEB, respectively. As a proof of concept, we
      coupled NMEB and DMEB to c(RGDfK), which is a small cyclic arginine-glycine
      aspartic acid (RGD) peptide, for targeting integrin alphavbeta3 NMEB and DMEB
      were radiolabeled with 64Cu and 90Y, respectively, and tested in xenograft
      models. Results: The resulting radiolabeled conjugates showed a prolonged
      circulation half-life and enhanced tumor accumulation in integrin alphavbeta3
      expressing tumors. Tumor uptake was markedly improved over that with NOTA- or
      DOTA-conjugated c(RGDfK). Tumor radiotherapy experiments in mice with 90Y-DMEB
      RGD showed promising results; existing tumors were eliminated. Conclusion:
      Conjugation of our novel add-on molecule, NMEB or DMEB, to potential tracers or
      therapeutic agents improved blood half-life and tumor uptake and could transform
      such agents into theranostic entities.

PMID- 27879374
TI  - Molecular determinants of KA1 domain-mediated autoinhibition and phospholipid
      activation of MARK1 kinase.
AB  - Protein kinases are frequently regulated by intramolecular autoinhibitory
      interactions between protein modules that are reversed when these modules bind
      other 'activating' protein or membrane-bound targets. One group of kinases, the
      MAP/microtubule affinity-regulating kinases (MARKs) contain a poorly understood
      regulatory module, the KA1 (kinase associated-1) domain, at their C-terminus. KA1
      domains from MARK1 and several related kinases from yeast to humans have been
      shown to bind membranes containing anionic phospholipids, and peptide ligands
      have also been reported. Deleting or mutating the C-terminal KA1 domain has been
      reported to activate the kinase in which it is found - also suggesting an
      intramolecular autoinhibitory role. Here, we show that the KA1 domain of human
      MARK1 interacts with, and inhibits, the MARK1 kinase domain. Using site-directed
      mutagenesis, we identify residues in the KA1 domain required for this
      autoinhibitory activity, and find that residues involved in autoinhibition and in
      anionic phospholipid binding are the same. We also demonstrate that a 'mini'
      MARK1 becomes activated upon association with vesicles containing anionic
      phospholipids, but only if the protein is targeted to these vesicles by a second
      signal. These studies provide a mechanistic basis for understanding how MARK1 and
      its relatives may require more than one signal at the membrane surface to control
      their activation at the correct location and time. MARK family kinases have been
      implicated in a plethora of disease states including Alzheimer's, cancer, and
      autism, so advancing our understanding of their regulatory mechanisms may
      ultimately have therapeutic value.

PMID- 27879375
TI  - The Role of Oxidative Stress in Koenimbine-Induced DNA Damage and Heat Shock
      Protein Modulation in HepG2 Cells.
AB  - BACKGROUND: Murraya koenigii (L.) Spreng, is a significant herb of traditional
      Ayurvedic system of medicine. Koenimbine, a carbazole alkaloid isolated from this
      plant holds antiproliferative and apoptotic effects. The aim of this study was to
      assess koenimbine-induced DNA damage and to clarify the role of free radicals in
      cell death mechanisms, using HepG2 cells. METHODS: The level of cytotoxicity was
      assayed by MTT assay. To elucidate the role of glutathione (GSH), the
      intracellular GSH level was analyzed. The effect of koenimbine in the cell
      mitochondria was evaluated using mitochondrial membrane potential (MMP) changes.
      Single cell gel electrophoresis assay was used to examine the level of DNA
      damage. Heat shock proteins, Hsp 70 and Hsp 90 expressions were checked at mRNA
      and protein level. Ascorbic acid and catalase were used as control antioxidants.
      RESULTS: It was observed that koenimbine considerably increased DNA damage in
      HepG2 cells at subcytotoxic concentrations. Koenimbine induced the increased
      levels of reactive oxygen species (ROS) and reduction of GSH level in HepG2
      cells, together with time-dependent loss of MMP. In addition, results clearly
      showed that koenimbine encouraged cells to express Hsp 70 and Hsp 90 in a
      concentration-dependent manner up to a concentration of 100 uM and a time
      dependent manner at 24-hour incubation both at transcriptional and translational
      levels. The antioxidant capacity of ascorbic acid was found to be not as
      prominent as to catalase throughout the study. CONCLUSION: Based on these data it
      can be concluded that koenimbine causes DNA strand breaks in HepG2 cells,
      probably through oxidative stress. Moreover, the oxidative stress induced was
      closely associated with MMP reduction and GSH depletion associated with HSP
      modulation at subcytotoxic concentration.

PMID- 27879378
TI  - Global news highlights.

PMID- 27879377
TI  - Promising Compounds From Murraya exotica for Cancer Metastasis Chemoprevention.
AB  - Most of the present anticancer drugs are highly cytotoxic and focus mainly on
      killing tumor cells rather than slowing the progress of cancer metastasis.
      Evidence has been reported that bridges the mechanisms of inflammation and tumor
      invasion. Therefore, we evaluated the potency in cancer metastasis
      chemoprevention of compounds and a coumarin extracted from Murraya exotica, which
      is known for its anti-inflammation bioactivity. By carrying out experiments in
      vitro, we found the root extracts more efficient than the leaf extracts in
      restraining cell migration of MDA-MB-231 cells, while leaf extracts presented
      slightly stronger inhibition of tumor cell adhesion at low concentrations. In
      addition, compared to root extracts, a novel coumarin identified previously from
      root extracts showed equal inhibition on cancer cell adhesion and less inhibition
      on cell migration. All extracts used in this study presented low cytotoxicity in
      vitro. Through comparison of the contents of leaf and root extracts from M
      exotica, several compounds are considered promising against cancer metastasis.
      This study evaluates the worth of further development of M exotica to find its
      effect on cancer metastasis chemoprevention.

PMID- 27879376
TI  - The Fractionated Toona sinensis Leaf Extract Induces Apoptosis of Human
      Osteosarcoma Cells and Inhibits Tumor Growth in a Murine Xenograft Model.
AB  - BACKGROUND: Osteosarcoma is a malignant bone tumor prevalent in adolescents with
      poor prognosis. Toona sinensis showed potent antiproliferation effect on lung,
      melatonin, ovary, colon, and liver cancers. However, the effects of the species
      on osteosarcoma cells are rarely investigated. RESULTS: In this study, we found
      fraction 1 of Toona sinensis leaf (TSL-1) resulted in inhibition of cell
      viability in MG-63, Saos-2, and U2OS osteosarcoma cell lines, while it only
      caused a moderate suppressive effect on normal osteoblasts. In addition, TSL-1
      significantly elevated lactate dehydrogenase leakage and induced apoptosis and
      necrosis in Saos-2 cells. TSL-1 increased mRNA expression of pro-apoptotic factor
      Bad. Most important, TSL-1 significantly suppressed Saos-2 xenograft tumor growth
      in nude mice by increasing caspase-3. The IC-50 of TSL-1 for the 3 tested
      osteosarcoma cells is around 1/9 of that for lung cancer cells. CONCLUSION: We
      demonstrated that TSL-1, a fractionated extract from TSL, caused significant
      cytotoxicity to osteosarcoma cells due to apoptosis. In vivo xenograft study
      showed that TSL-1 suppressed the growth of osteosarcoma cells at least in part by
      inducing apoptosis. Our results indicate that TSL-1 has potential to be a
      promising anti-osteosarcoma adjuvant functional plant extract.

PMID- 27879379
TI  - Performance of the PneuX System: A Bench Study Comparison With 4 Other
      Endotracheal Tube Cuffs.
AB  - BACKGROUND: Cuff design affects microaspiration, a risk factor for pneumonia. We
      questioned whether the PneuX low-volume fold-free cuff design would prevent cuff
      leakage and maintain the same tracheal wall pressure as high-volume, low-pressure
      (HVLP) cuffs. METHODS: We evaluated 4 HVLP-cuffed endotracheal tubes (ETTs), Hi
      Lo (polyvinyl chloride [PVC]), Microcuff (polyurethane [PU]), SealGuard (PU +
      tapered), and TaperGuard (PVC + tapered), and the PneuX with its dedicated
      tracheal seal monitor. In Part 1, we determined tracheal wall pressure using each
      cuff's capacity to support water columns across recommended intracuff pressures.
      In Part 2, we evaluated the tracheal seal monitor function at recommended
      settings. In Part 3, we compared leakage volumes of all ETTs during 30 min of
      simulated mechanical ventilation or during 8 h if no leak occurred. Parts 1 and 3
      were performed with/without lubrication and PEEP. RESULTS: In Part 1, PneuX cuffs
      exerted an average tracheal wall pressure of 27.4 +/- 2.4 cm H2O at the
      recommended intracuff pressure of approximately 80 cm H2O. Tracheal wall pressure
      did not differ among HVLP cuffs (19.6 +/- 1.4 to 29.5 +/- 1.4 cm H2O). In Part 2,
      preinflation intracuff pressure affected the time to obtain tracheal seal monitor
      pressure attainment (P < .01). The tracheal seal monitor generated average
      calculated tracheal wall pressure of 33.4 +/- 1.2 cm H2O. In Part 3, PneuX ETT
      showed no leak across 8 h for all trials. Overall, leakage volume was lower with
      PU (P < .01) and PneuX (P < .01) than with PVC cuffs, regardless of shape, and
      lower with lubrication and/or PEEP (all P < .01). In each HVLP cuff, lubrication
      alone eliminated leak at an intracuff pressure of <=30 cm H2O. CONCLUSIONS: The
      PneuX cuff generally exerted acceptable tracheal wall pressure, but the tracheal
      wall pressure monitor allowed pressures exceeding 30 cm H2O in some trials and
      was the only ETT to prevent leak in all tests. For HVLP cuffs, leak was reduced
      by PU and PEEP and eliminated by lubrication.

PMID- 27879381
TI  - Pediatric Prolonged Mechanical Ventilation: Considerations for Definitional
      Criteria.
AB  - BACKGROUND: A 2005 consensus conference led by the National Association for
      Medical Direction of Respiratory Care (NAMDRC) defined prolonged mechanical
      ventilation (PMV) for adults as invasive and/or noninvasive mechanical
      ventilation (NIV) for >= 21 consecutive days for >= 6 h/d. In children, no such
      consensus definition exists. This results in substantial variability in
      definitional criteria, making study of the impact and outcomes of PMV across and
      within settings problematic. The objective of this work was to identify how PMV
      for children and neonates is described in the literature and to outline
      pediatric/neonatal considerations related to PMV, with the goal of proposing a
      pediatric/neonatal adaptation to the NAMDRC definition. METHODS: We searched
      electronic databases for studies describing PMV in children. We extracted
      definitional criteria and developed recommendations based on the literature
      review and our clinical experience. RESULTS: Of the 416 citations obtained, 87
      met inclusion criteria, totaling 34,255 subjects. Identified criteria for the
      pediatric PMV definition included: number of consecutive days of mechanical
      ventilation (ranging from 6 h to 3 months), inclusion of NIV, time spent off the
      ventilator during weaning (considered as same ventilation episode), and
      importance of chronological age (term neonates) and postmenstrual age for preterm
      neonates. We considered high-flow nasal cannula; however, we determined that its
      current role as a weaning adjunct is unclear. CONCLUSIONS: Therefore, we
      developed the following recommendations for the pediatric PMV definition: >= 21
      consecutive days (after 37 weeks postmenstrual age) of ventilation for >= 6 h/d
      considering invasive ventilation and NIV and including short interruptions (< 48
      h) of ventilation during the weaning process as the same episode of ventilation.
      We propose a definition of pediatric PMV that incorporates the number of
      consecutive days of mechanical ventilation while taking into account use of NIV
      and lung maturity and including short interruptions during the weaning process.

PMID- 27879380
TI  - Performance of Leak Compensation in All-Age ICU Ventilators During Volume
      Targeted Neonatal Ventilation: A Lung Model Study.
AB  - BACKGROUND: Volume-targeted ventilation is increasingly used in low birthweight
      infants because of the potential for reducing volutrauma and avoiding hypocapnea.
      However, it is not known what level of air leak is acceptable during neonatal
      volume-targeted ventilation when leak compensation is activated concurrently.
      METHODS: Four ICU ventilators (Servo-i, PB980, V500, and Avea) were compared in
      available invasive volume-targeted ventilation modes (pressure control continuous
      spontaneous ventilation [PC-CSV] and pressure control continuous mandatory
      ventilation [PC-CMV]). The Servo-i and PB980 were tested with (+) and without (-)
      their proximal flow sensor. The V500 and Avea were tested with their proximal
      flow sensor as indicated by their manufacturers. An ASL 5000 lung model was used
      to simulate 4 neonatal scenarios (body weight 0.5, 1, 2, and 4 kg). The ASL 5000
      was ventilated via an endotracheal tube with 3 different leaks. Two minutes of
      data were collected after each change in leak level, and the asynchrony index was
      calculated. Tidal volume (VT) before and after the change in leak was assessed.
      RESULTS: The differences in delivered VT between before and after the change in
      leak were within +/-5% in all scenarios with the PB980 (-/+) and V500. With the
      Servo-i (-/+), baseline VT was >=10% greater than set VT during PC-CSV, and
      delivered VT markedly changed with leak. The Avea demonstrated persistent high VT
      in all leak scenarios. Across all ventilators, the median asynchrony index was 1%
      (interquartile range 0-27%) in PC-CSV and 1.8% (0-45%) in PC-CMV. The median
      asynchrony index was significantly higher in the Servo-i (-/+) than in the PB980
      (-/+) and V500 in 1 and 2 kg scenarios during PC-CSV and PC-CMV. CONCLUSIONS: The
      PB980 and V500 were the only ventilators to acclimate to all leak scenarios and
      achieve targeted VT. Further clinical investigation is needed to validate the use
      of leak compensation during neonatal volume-targeted ventilation.

PMID- 27879382
TI  - Veteran Preferences Regarding Wireless Management of Positive Airway Pressure for
      Obstructive Sleep Apnea at a Tertiary Health-Care System.
AB  - BACKGROUND: Timely monitoring of obstructive sleep apnea (OSA) therapy can be a
      challenge amid conflicting pressures of rising patient volume and shortage of
      sleep medicine providers. Positive airway pressure (PAP) devices with wireless
      modem technology have the potential to improve patient access to care and
      streamline work load, yet little is known about patient attitudes toward
      telehealth integration among veterans with sleep apnea. As part of a larger
      quality improvement initiative at the Veterans Affairs (VA) Puget Sound Health
      Care System, we elicited veterans' preferences toward modem versus traditional
      PAP data download, including patient attitudes and factors affecting those
      preferences. METHODS: We conducted an anonymous survey of veterans without
      previous CPAP experience presenting for initial device setup and training at VA
      Puget Sound PAP clinics. Surveys assessed subject demographics, PAP download
      preferences (modem vs mail), and Likert-type scale ratings of importance placed
      on factors including convenience and information privacy. Using multinomial
      logistic regression, we examined the association between convenience rating and
      download preference, adjusting for information privacy rating, age, and commute
      time. RESULTS: Of 444 surveys analyzed, respondents were primarily male with a
      mean age of 52 y. Most respondents reported taking >= 30 min to commute to the
      PAP clinic. Convenience was rated as the most important factor affecting download
      preferences. Veteran preferences regarding PAP download method were mixed, with
      47% preferring modem, 38% preferring memory card mail-in, and 15% undecided. A
      higher rating of convenience was significantly associated with modem preference,
      both before and after adjustment for information privacy rating, commute time,
      and veteran age (adjusted relative risk ratio 1.67, P < .001, 95% CI 1.40-1.99).
      CONCLUSIONS: PAP data download preferences were mixed among new veteran users.
      Veterans placed a high value on the potentially competing concerns of convenience
      and information privacy. Veterans preferring modem factored convenience as
      important in their decision making, independent of privacy concerns.

PMID- 27879383
TI  - High-Flow Nasal Cannula in Critically Ill Subjects With or at Risk for
      Respiratory Failure: A Systematic Review and Meta-Analysis.
AB  - High-flow nasal cannula (HFNC) oxygen delivery has been gaining attention as an
      alternative means of respiratory support for critically ill patients, with recent
      studies suggesting equivalent outcomes when compared with other forms of oxygen
      therapy delivery. The main objective of this review was to extract current data
      about the efficacy of HFNC in critically ill subjects with or at risk for
      respiratory failure. We performed a systematic review of publications (from
      database inception to October 2015) that evaluated HFNC in critically ill
      subjects with or at risk for acute respiratory failure and performed a meta
      analysis comparing HFNC with noninvasive ventilation (NIV) and with standard
      oxygen therapy regarding major outcomes: incidence of invasive mechanical
      ventilation and ICU mortality. A total of 9 studies were included. HFNC was not
      associated with a reduction in the incidence of invasive mechanical ventilation
      compared with NIV (odds ratio [OR] 0.83, 95% CI 0.57-1.20, P = .31) or standard
      oxygen therapy (OR 0.49, 95% CI 0.22-1.08, P = .17). Additionally, HFNC use did
      not reduce ICU mortality compared with NIV (OR 0.72, 95% CI 0.23-2.21, P = .56)
      or with standard oxygen therapy (OR 0.69, 95% CI 0.33-1.42, P = .29). There was a
      trend toward better oxygenation compared with conventional oxygen therapy but a
      worse gas exchange compared with NIV. At this moment, HFNC therapy seems not to
      be superior to conventional oxygen therapy or NIV in terms of invasive mechanical
      ventilation rate or ICU mortality in critical illness, but new studies are needed
      to determine whether HFNC is associated with any difference in major outcomes
      when compared with other techniques.

PMID- 27879384
TI  - Videolaryngoscopy With Noninvasive Ventilation in Subjects With Upper-Airway
      Obstruction.
AB  - BACKGROUND: Noninvasive ventilation (NIV) titration may be difficult when dynamic
      airway obstruction episodes persist, even with high expiratory positive airway
      pressure (EPAP). We aimed to determine the usefulness of videolaryngoscopy during
      NIV for identifying mechanisms and sites of obstruction and for providing a guide
      for their resolution in difficult-to-titrate subjects. METHODS: When obstructions
      during NIV were present in the built-in software, EPAP was raised to 12 cm H2O.
      If obstructions persisted, a polygraphy during NIV was performed; if the events
      occurred with effort, a videolaryngoscopy with nasal and oronasal masks in awake
      subjects was performed. RESULTS: In a population of 208 subjects in whom NIV was
      initiated, 13 were identified as difficult to titrate with persistent
      obstructions during NIV despite an EPAP of 12 cm H2O. Videolaryngoscopy during
      NIV was able to identify the mechanism and the site of obstruction in all cases.
      The obstruction under oronasal mask ventilation was due to soft-palate (velum)
      collapse in 4 subjects, to epiglottic backward movement in 5 other subjects, and
      to tongue-base obstruction reducing the retroglossal space in 3 more.
      Videolaryngoscopy during NIV demonstrated improvement in 9 subjects (69%) upon
      changing to nasal mask and suggested a possible surgical approach in 2 (15%); in
      one of these 2 subjects, a successful uvulopalatopharyngoplasty was performed.
      CONCLUSIONS: The use of videolaryngoscopy during NIV in difficult-to-titrate
      patients may help to identify the sites and mechanisms of obstruction and in some
      cases may improve quality of ventilation.

PMID- 27879385
TI  - FIO2 in an Adult Model Simulating High-Flow Nasal Cannula Therapy.
AB  - BACKGROUND: High-flow nasal cannula therapy (HFNC) is widely used for patients
      with acute respiratory failure. HFNC has a number of physiological effects.
      Although FIO2 is considered to be constant, because HFNC is an open system, FIO2
      varies according to inspiratory flow, tidal volume (VT), and HFNC gas flow. We
      investigated the influence of HFNC gas flow and other respiratory parameters on
      FIO2 during HFNC. METHODS: We evaluated an HFNC system and, for comparison, a
      conventional oxygen therapy system. The HFNC apparatus was composed of an
      air/oxygen blender, a heated humidifier, an inspiratory limb, and small, medium,
      and large nasal prongs. HFNC gas flow was set at 20, 40, and 60 L/min, and FIO2
      was set at 0.3, 0.5, and 0.7. We measured FIO2 for 1-min intervals using an
      oxygen analyzer and extracted data for the final 3 breaths of each interval.
      Spontaneous breathing was simulated using a mechanical ventilator connected to
      the muscle compartment of a model lung. The lung compartment passively moved with
      the muscle compartment, thus inspiring ambient air via a ventilator limb. With a
      decelerating flow waveform, simulated VT was set at 300, 500, and 700 mL,
      breathing frequency at 10 and 20 breaths/min, and inspiratory time at 1.0 s.
      RESULTS: With HFNC gas flow of 20 and 40 L/min, at all set FIO2 values,
      inspiratory oxygen concentration varied with VT (P < .001). As the set value for
      FIO2 increased, the difference between set FIO2 and measured FIO2 increased.
      Neither breathing frequency nor prong size influenced FIO2 . CONCLUSIONS: During
      HFNC with simulated spontaneous breathing, when HFNC gas flow was 60 L/min,
      measured FIO2 was similar to set FIO2 at 0.3 and 0.5, whereas at 0.7, as VT
      increased, measured FIO2 decreased slightly. However, at 20 or 40 L/min, changes
      in VT related with deviation from set FIO2 .

PMID- 27879386
TI  - Mitochondrial calcium homeostasis: Implications for neurovascular and
      neurometabolic coupling.
AB  - Mitochondrial function is critical to maintain high rates of oxidative metabolism
      supporting energy demands of both spontaneous and evoked neuronal activity in the
      brain. Mitochondria not only regulate energy metabolism, but also influence
      neuronal signaling. Regulation of "energy metabolism" and "neuronal signaling"
      (i.e. neurometabolic coupling), which are coupled rather than independent can be
      understood through mitochondria's integrative functions of calcium ion (Ca2+)
      uptake and cycling. While mitochondrial Ca2+ do not affect hemodynamics directly,
      neuronal activity changes are mechanistically linked to functional hyperemic
      responses (i.e. neurovascular coupling). Early in vitro studies lay the
      foundation of mitochondrial Ca2+ homeostasis and its functional roles within
      cells. However, recent in vivo approaches indicate mitochondrial Ca2+ homeostasis
      as maintained by the role of mitochondrial Ca2+ uniporter (mCU) influences system
      level brain activity as measured by a variety of techniques. Based on earlier
      evidence of subcellular cytoplasmic Ca2+ microdomains and cellular bioenergetic
      states, a mechanistic model of Ca2+ mobilization is presented to understand
      systems-level neurovascular and neurometabolic coupling. This integrated view
      from molecular and cellular to the systems level, where mCU plays a major role in
      mitochondrial and cellular Ca2+ homeostasis, may explain the wide range of
      activation-induced coupling across neuronal activity, hemodynamic, and metabolic
      responses.

PMID- 27879387
TI  - Rice Cellulose SynthaseA8 Plant-Conserved Region Is a Coiled-Coil at the
      Catalytic Core Entrance.
AB  - The crystallographic structure of a rice (Oryza sativa) cellulose synthase,
      OsCesA8, plant-conserved region (P-CR), one of two unique domains in the
      catalytic domain of plant CesAs, was solved to 2.4 A resolution. Two antiparallel
      alpha-helices form a coiled-coil domain linked by a large extended connector loop
      containing a conserved trio of aromatic residues. The P-CR structure was fit into
      a molecular envelope for the P-CR domain derived from small-angle X-ray
      scattering data. The P-CR structure and molecular envelope, combined with a
      homology-based chain trace of the CesA8 catalytic core, were modeled into a
      previously determined CesA8 small-angle X-ray scattering molecular envelope to
      produce a detailed topological model of the CesA8 catalytic domain. The predicted
      position for the P-CR domain from the molecular docking models places the P-CR
      connector loop into a hydrophobic pocket of the catalytic core, with the coiled
      coil aligned near the entrance of the substrate UDP-glucose into the active site.
      In this configuration, the P-CR coiled-coil alone is unlikely to regulate
      substrate access to the active site, but it could interact with other domains of
      CesA, accessory proteins, or other CesA catalytic domains to control substrate
      delivery.

PMID- 27879388
TI  - An Ethylene-Induced Regulatory Module Delays Flower Senescence by Regulating
      Cytokinin Content.
AB  - In many plant species, including rose (Rosa hybrida), flower senescence is
      promoted by the gaseous hormone ethylene and inhibited by the cytokinin (CTK)
      class of hormones. However, the molecular mechanisms underlying these
      antagonistic effects are not well understood. In this study, we characterized the
      association between a pathogenesis-related PR-10 family gene from rose (RhPR10.1)
      and the hormonal regulation of flower senescence. Quantitative reverse
      transcription PCR analysis showed that RhPR10.1 was expressed at high levels
      during senescence in different floral organs, including petal, sepal, receptacle,
      stamen, and pistil, and that expression was induced by ethylene treatment.
      Silencing of RhPR10.1 expression in rose plants by virus-induced gene silencing
      accelerated flower senescence, which was accompanied by a higher ion leakage rate
      in the petals, as well as increased expression of the senescence marker gene
      RhSAG12 CTK content and the expression of three CTK signaling pathway genes were
      reduced in RhPR10.1-silenced plants, and the accelerated rate of petal senescence
      that was apparent in the RhPR10.1-silenced plants was restored to normal levels
      by CTK treatment. Finally, RhHB6, a homeodomain-Leu zipper I transcription
      factor, was observed to bind to the RhPR10.1 promoter, and silencing of its
      expression also promoted flower senescence. Our results reveal an ethylene
      induced RhHB6-RhPR10.1 regulatory module that functions as a brake of ethylene
      promoted senescence through increasing the CTK content.

PMID- 27879389
TI  - VPS36-Dependent Multivesicular Bodies Are Critical for Plasmamembrane Protein
      Turnover and Vacuolar Biogenesis.
AB  - Most eukaryotic cells target ubiquitinated plasma membrane (PM) proteins for
      vacuolar degradation in response to environmental and developmental cues. This
      process involves endosomal sorting complexes required for transport (ESCRT).
      However, little is known about the cellular mechanisms of ESCRTs in plants. Here,
      we studied the function of one ESCRT-II component, VPS36, which shows ubiquitin
      binding activity and may form a putative ESCRT-II with VPS22 and VPS25 in
      Arabidopsis (Arabidopsis thaliana). Recessive mutation of the ubiquitously
      expressed VPS36 causes multiple defects, including delayed embryogenesis,
      defective root elongation, and limited expansion of cotyledons, and these effects
      can be complemented by its genomic DNA. Abnormal intracellular compartments
      containing several membrane transporters, including members of the PIN-FORMEDs,
      AUXIN RESISTANT 1, and PIP1 families, were found in vps36-1 plants. Employing a
      genetic approach to cross vps36-1/+ with transgenic plants harboring various
      fluorescent protein-tagged organelle markers, as well as fluorescent probe and
      ultrastructural approaches, revealed PM proteins in microsomal fractions from
      vps36-1 seedlings and demonstrated that VPS36 is critical for forming
      multivesicular bodies and vacuolar biogenesis for protein degradation. Our study
      shows that functional VPS36 is essential for a proper endosomal sorting pathway
      and for vacuolar biogenesis in Arabidopsis.

PMID- 27879391
TI  - Rice Leaf Angle and Grain Size Are Affected by the OsBUL1 Transcriptional
      Activator Complex.
AB  - Rice atypical HLH protein Oryza sativa BRASSINOSTEROID UPREGULATED 1-LIKE1
      (OsBUL1) is preferentially expressed in the lamina joint where it controls cell
      elongation and positively affects leaf angles. OsBUL1 knockout mutant (osbul1)
      and transgenic rice for double-stranded RNA interference (dsRNAi) of OsBUL1
      produced erect leaves with smaller grains, whereas OsBUL1 overexpressors and an
      activation tagging line of OsBUL1 exhibited increased lamina inclination and
      grain size. Moreover, OsBUL1 expression was induced by brassinolide (BL) and
      osbul1 did not respond to BL treatment. To understand the molecular network of
      OsBUL1 function in rice, we isolated a novel OsBUL1-interacting protein, LO9-177,
      an uncharacterized protein containing a KxDL motif, and functionally studied it
      with respect to the lamina inclination and grain size of rice. OsBUL1 COMPLEX1
      (OsBC1) is a basic helix-loop-helix (bHLH) transcriptional activator that
      interacts with OsBUL1 only in the presence of LO9-177 forming a possible trimeric
      complex for cell elongation in the lamina joint of rice. Expression of OsBC1 is
      also upregulated by BL and has a similar pattern to that of OsBUL1 Transgenic
      rice plants expressing OsBC1 under the control of OsBUL1 promoter showed
      increased grain size as well as leaf bending, while transgenic lines for dsRNAi
      and/or expressing a dominant repressor form of OsBC1 displayed reduced plant
      height and grain size. Together, these results demonstrated that a novel protein
      complex consisting of OsBUL1, LO9-177, and OsBC1 is associated with the HLH-bHLH
      system, providing new insight into the molecular functional network based on HLH
      bHLH proteins for cell elongation.

PMID- 27879390
TI  - Phosphorylation of MAP65-1 by Arabidopsis Aurora Kinases Is Required for
      Efficient Cell Cycle Progression.
AB  - Aurora kinases are key effectors of mitosis. Plant Auroras are functionally
      divided into two clades. The alpha Auroras (Aurora1 and Aurora2) associate with
      the spindle and the cell plate and are implicated in controlling formative
      divisions throughout plant development. The beta Aurora (Aurora3) localizes to
      centromeres and likely functions in chromosome separation. In contrast to the
      wealth of data available on the role of Aurora in other kingdoms, knowledge on
      their function in plants is merely emerging. This is exemplified by the fact that
      only histone H3 and the plant homolog of TPX2 have been identified as Aurora
      substrates in plants. Here we provide biochemical, genetic, and cell biological
      evidence that the microtubule-bundling protein MAP65-1-a member of the
      MAP65/Ase1/PRC1 protein family, implicated in central spindle formation and
      cytokinesis in animals, yeasts, and plants-is a genuine substrate of alpha Aurora
      kinases. MAP65-1 interacts with Aurora1 in vivo and is phosphorylated on two
      residues at its unfolded tail domain. Its overexpression and down-regulation
      antagonistically affect the alpha Aurora double mutant phenotypes. Phospho-mutant
      analysis shows that Aurora contributes to the microtubule bundling capacity of
      MAP65-1 in concert with other mitotic kinases.

PMID- 27879394
TI  - Selective control of up-regulated and down-regulated genes by temporal patterns
      and doses of insulin.
AB  - Secretion of insulin transiently increases after eating, resulting in a high
      circulating concentration. Fasting limits insulin secretion, resulting in a low
      concentration of insulin in the circulation. We analyzed transcriptional
      responses to different temporal patterns and doses of insulin in the hepatoma FAO
      cells and identified 13 up-regulated and 16 down-regulated insulin-responsive
      genes (IRGs). The up-regulated IRGs responded more rapidly than did the down
      regulated IRGs to transient stepwise or pulsatile increases in insulin
      concentration, whereas the down-regulated IRGs were repressed at lower
      concentrations of insulin than those required to stimulate the up-regulated IRGs.
      Mathematical modeling of the insulin response as two stages-(i) insulin signaling
      to transcription and (ii)transcription and mRNA stability-indicated that the
      first stage was the more rapid stage for the down-regulated IRGs, whereas the
      second stage of transcription was the more rapid stage for the up-regulated IRGs.
      A subset of the IRGs that were up-regulated or down-regulated in the FAO cells
      was similarly regulated in the livers of rats injected with a single dose of
      insulin. Thus, not only can cells respond to insulin but they can also interpret
      the intensity and pattern of signal to produce distinct transcriptional
      responses. These results provide insight that may be useful in treating obesity
      and type 2 diabetes associated with aberrant insulin production or tissue
      responsiveness.

PMID- 27879393
TI  - Natural Variation of Molecular and Morphological Gibberellin Responses.
AB  - Although phytohormones such as gibberellins are essential for many conserved
      aspects of plant physiology and development, plants vary greatly in their
      responses to these regulatory compounds. Here, we use genetic perturbation of
      endogenous gibberellin levels to probe the extent of intraspecific variation in
      gibberellin responses in natural accessions of Arabidopsis (Arabidopsis
      thaliana). We find that these accessions vary greatly in their ability to buffer
      the effects of overexpression of GA20ox1, encoding a rate-limiting enzyme for
      gibberellin biosynthesis, with substantial differences in bioactive gibberellin
      concentrations as well as transcriptomes and growth trajectories. These findings
      demonstrate a surprising level of flexibility in the wiring of regulatory
      networks underlying hormone metabolism and signaling.

PMID- 27879392
TI  - Characterization of Class III Peroxidases from Switchgrass.
AB  - Class III peroxidases (CIIIPRX) catalyze the oxidation of monolignols, generate
      radicals, and ultimately lead to the formation of lignin. In general, CIIIPRX
      genes encode a large number of isozymes with ranges of in vitro substrate
      specificities. In order to elucidate the mode of substrate specificity of these
      enzymes, we characterized one of the CIIIPRXs (PviPRX9) from switchgrass (Panicum
      virgatum), a strategic plant for second-generation biofuels. The crystal
      structure, kinetic experiments, molecular docking, as well as expression patterns
      of PviPRX9 across multiple tissues and treatments, along with its levels of
      coexpression with the majority of genes in the monolignol biosynthesis pathway,
      revealed the function of PviPRX9 in lignification. Significantly, our study
      suggested that PviPRX9 has the ability to oxidize a broad range of
      phenylpropanoids with rather similar efficiencies, which reflects its role in the
      fortification of cell walls during normal growth and root development and in
      response to insect feeding. Based on the observed interactions of
      phenylpropanoids in the active site and analysis of kinetics, a catalytic
      mechanism involving two water molecules and residues histidine-42, arginine-38,
      and serine-71 was proposed. In addition, proline-138 and gluntamine-140 at the
      137P-X-P-X140 motif, leucine-66, proline-67, and asparagine-176 may account for
      the broad substrate specificity of PviPRX9. Taken together, these observations
      shed new light on the function and catalysis of PviPRX9 and potentially benefit
      efforts to improve biomass conservation properties in bioenergy and forage crops.

PMID- 27879395
TI  - A computationally identified compound antagonizes excess FGF-23 signaling in
      renal tubules and a mouse model of hypophosphatemia.
AB  - Fibroblast growth factor-23 (FGF-23) interacts with a binary receptor complex
      composed of alpha-Klotho (alpha-KL) and FGF receptors (FGFRs) to regulate
      phosphate and vitamin D metabolism in the kidney. Excess FGF-23 production, which
      causes hypophosphatemia, is genetically inherited or occurs with chronic kidney
      disease. Among other symptoms, hypophosphatemia causes vitamin D deficiency and
      the bone-softening disorder rickets. Current therapeutics that target the
      receptor complex have limited utility clinically. Using a computationally driven,
      structure-based, ensemble docking and virtual high-throughput screening approach,
      we identified four novel compounds predicted to selectively inhibit FGF-23
      induced activation of the FGFR/alpha-KL complex. Additional modeling and
      functional analysis found that Zinc13407541 bound to FGF-23 and disrupted its
      interaction with the FGFR1/alpha-KL complex; experiments in a heterologous cell
      expression system showed that Zinc13407541 selectivity inhibited alpha-KL
      dependent FGF-23 signaling. Zinc13407541 also inhibited FGF-23 signaling in
      isolated renal tubules ex vivo and partially reversed the hypophosphatemic
      effects of excess FGF-23 in a mouse model. These chemical probes provide a
      platform to develop lead compounds to treat disorders caused by excess FGF-23.

PMID- 27879396
TI  - Integrating network reconstruction with mechanistic modeling to predict cancer
      therapies.
AB  - Signal transduction networks are often rewired in cancer cells. Identifying these
      alterations will enable more effective cancer treatment. We developed a
      computational framework that can identify, reconstruct, and mechanistically model
      these rewired networks from noisy and incomplete perturbation response data and
      then predict potential targets for intervention. As a proof of principle, we
      analyzed a perturbation data set targeting epidermal growth factor receptor
      (EGFR) and insulin-like growth factor 1 receptor (IGF1R) pathways in a panel of
      colorectal cancer cells. Our computational approach predicted cell line-specific
      network rewiring. In particular, feedback inhibition of insulin receptor
      substrate 1 (IRS1) by the kinase p70S6K was predicted to confer resistance to
      EGFR inhibition, suggesting that disrupting this feedback may restore sensitivity
      to EGFR inhibitors in colorectal cancer cells. We experimentally validated this
      prediction with colorectal cancer cell lines in culture and in a zebrafish (Danio
      rerio) xenograft model.

PMID- 27879397
TI  - "All That Necroses Is Not Toxic Epidermal Necrolysis".

PMID- 27879398
TI  - Spectral Unmixing Plate Reader: High-Throughput, High-Precision FRET Assays in
      Living Cells.
AB  - We have developed a microplate reader that records a complete high-quality
      fluorescence emission spectrum on a well-by-well basis under true high-throughput
      screening (HTS) conditions. The read time for an entire 384-well plate is less
      than 3 min. This instrument is particularly well suited for assays based on
      fluorescence resonance energy transfer (FRET). Intramolecular protein biosensors
      with genetically encoded green fluorescent protein (GFP) donor and red
      fluorescent protein (RFP) acceptor tags at positions sensitive to structural
      changes were stably expressed and studied in living HEK cells. Accurate
      quantitation of FRET was achieved by decomposing each observed spectrum into a
      linear combination of four component (basis) spectra (GFP emission, RFP emission,
      water Raman, and cell autofluorescence). Excitation and detection are both
      conducted from the top, allowing for thermoelectric control of the sample
      temperature from below. This spectral unmixing plate reader (SUPR) delivers an
      unprecedented combination of speed, precision, and accuracy for studying ensemble
      averaged FRET in living cells. It complements our previously reported
      fluorescence lifetime plate reader, which offers the feature of resolving
      multiple FRET populations within the ensemble. The combination of these two
      direct waveform-recording technologies greatly enhances the precision and
      information content for HTS in drug discovery.

PMID- 27879399
TI  - Bone subtraction radiography in adult patients with cystic fibrosis.
AB  - Background Bone subtraction radiography allows reading pulmonary changes of chest
      radiographs more accurately without superimposition of bones. Purpose To evaluate
      the value of bone subtraction chest radiography using dual energy (DE) bone
      subtracted lung images compared to conventional radiographs (CR) in adult
      patients with cystic fibrosis (CF). Material and Methods Forty-nine DE
      radiographs of 24 patients (16 men) with CF (mean age, 32 years; age range, 18-71
      years) were included. Lung function tests were performed within 10 days of the
      radiographs. Two radiologists evaluated all CR, DE, and CR + DE radiographs using
      the modified Chrispin-Norman score (CNS) and a five-point score for the
      confidence. Findings were statistically evaluated by Friedman ANOVA and Wilcoxon
      matched-pairs test. Results There was significant difference of CNS between CR
      and DE ( P = 0.044) as well as CR and CR + DE ( P < 0.001). CNS of CR images
      showed moderate correlation with FEV1% (R = 0.287, P = 0.046) while DE and CR +
      DE correlated poorly with FEV1% (R = 0.023, P = 0.874 and R = 0.04, P = 0.785). A
      higher confidence was achieved with bone-subtracted radiographs compared to
      radiographs alone (median, CR 3.3, DE 3.9, CR + DE 4.1, for both P < 0.001).
      Conclusion DE radiographs are reliable for the evaluation of adult patients with
      CF in acute exacerbation. For yearly surveillance, CR and DE radiographs may play
      a limited role. However, in clinical routine, DE radiographs are useful for adult
      CF patients and may depict more accurately inflammatory changes than CR.

PMID- 27879401
TI  - Diabetic Cardiomyopathy: The Case for a Role of Fructose in Disease Etiology.
AB  - A link between excess dietary sugar and cardiac disease is clearly evident and
      has been largely attributed to systemic metabolic dysregulation. Now a new
      paradigm is emerging, and a compelling case can be made that fructose-associated
      heart injury may be attributed to the direct actions of fructose on
      cardiomyocytes. Plasma and cardiac fructose levels are elevated in patients with
      diabetes, and evidence suggests that some unique properties of fructose (vs.
      glucose) have specific cardiomyocyte consequences. Investigations to date have
      demonstrated that cardiomyocytes have the capacity to transport and utilize
      fructose and express all of the necessary proteins for fructose metabolism. When
      dietary fructose intake is elevated and myocardial glucose uptake compromised by
      insulin resistance, increased cardiomyocyte fructose flux represents a hazard
      involving unregulated glycolysis and oxidative stress. The high reactivity of
      fructose supports the contention that fructose accelerates subcellular hexose
      sugar-related protein modifications, such as O-GlcNAcylation and advanced
      glycation end product formation. Exciting recent discoveries link heart failure
      to induction of the specific high-affinity fructose-metabolizing enzyme,
      fructokinase, in an experimental setting. In this Perspective, we review key
      recent findings to synthesize a novel view of fructose as a cardiopathogenic
      agent in diabetes and to identify important knowledge gaps for urgent research
      focus.

PMID- 27879402
TI  - Hyperpolarized 13C Magnetic Resonance Treatment Response Monitoring: A New
      Paradigm for Multiorgan Metabolic Assessment of Pharmacological Interventions?

PMID- 27879403
TI  - CIN85: Implications for the Development of Proteinuria in Diabetic Nephropathy.

PMID- 27879405
TI  - Does Citrulline Sit at the Nexus of Metformin's Pleotropic Effects on Metabolism
      and Mediate Its Salutatory Effects in Individuals With Type 2 Diabetes?

PMID- 27879406
TI  - Type 2 Diabetes Genes Gleaned by Making a beta-Cell Screen Routine.

PMID- 27879404
TI  - Targeting CITED2 for Angiogenesis in Obesity and Insulin Resistance.

PMID- 27879408
TI  - A Dual-Label Time-Resolved Fluorescence Immunoassay for the Simultaneous
      Determination of Cardiac Troponin T and Myoglobin.
AB  - The aim of this study was to establish a dual-label time-resolved fluorescence
      immunoassay (TRFIA) for the simultaneous determination of cardiac troponin T
      (cTnT) and myoglobin (MYO) for the early diagnosis of acute myocardial
      infarction. The sandwich immunoassay was used to detect the concentration of cTnT
      and MYO in serum. cTnT and MYO in serum were captured by anti-cTnT and anti-MYO
      antibodies immobilized on microtiter wells and then banded together with another
      anti-cTnT and anti-MYO labeled with europium(III) Sm3+ and samarium(III) Eu3+
      chelates, followed by fluorescence measurement using time-resolved fluorometry.
      The performance of this TRFIA was evaluated using the clinical serum and compared
      with the commercial assays. The linear correlation coefficients ( R2) of the cTnT
      and MYO standard curves were 0.9993 and 0.9995, respectively. The sensitivity for
      cTnT detection was 2.21 pg/mL (linear dynamic range was 3.24-963.71 pg/mL), and
      the average recovery was 100.57%. The sensitivity for MYO detection was 3.24
      ng/mL (linear dynamic range was 4.95-976.85 ng/mL), and the average recovery was
      99.79%. High correlation coefficients ( R2) were obtained between the commercial
      assays and dual-label TRFIA ( R2 = 0.999). The present dual-label TRFIA has high
      sensitivity, specificity, and accuracy in clinical sample analysis. It is a good
      alternative to the single-label diagnostic methods.

PMID- 27879409
TI  - New Technologies for Rapid Bacterial Identification and Antibiotic Resistance
      Profiling.
AB  - Conventional approaches to bacterial identification and drug susceptibility
      testing typically rely on culture-based approaches that take 2 to 7 days to
      return results. The long turnaround times contribute to the spread of infectious
      disease, negative patient outcomes, and the misuse of antibiotics that can
      contribute to antibiotic resistance. To provide new solutions enabling faster
      bacterial analysis, a variety of approaches are under development that leverage
      single-cell analysis, microfluidic concentration and detection strategies, and
      ultrasensitive readout mechanisms. This review discusses recent advances in this
      area and the potential of new technologies to enable more effective management of
      infectious disease.

PMID- 27879411
TI  - The role of technology in minimally invasive surgery: state of the art, recent
      developments and future directions.
AB  - The diffusion of minimally invasive surgery has thrived in recent years,
      providing substantial benefits over traditional techniques for a number of
      surgical interventions. This rapid growth has been possible due to significant
      advancements in medical technology, which partly solved some of the technical and
      clinical challenges associated with minimally invasive techniques. The issues
      that still limit its widespread adoption for some applications include the
      limited field of view; reduced manoeuvrability of the tools; lack of haptic
      feedback; loss of depth perception; extended learning curve; prolonged operative
      times and higher financial costs. The present review discusses some of the main
      recent technological advancements that fuelled the uptake of minimally invasive
      surgery, focussing especially on the areas of imaging, instrumentation, cameras
      and robotics. The current limitations of state-of-the-art technology are
      identified and addressed, proposing future research directions necessary to
      overcome them.

PMID- 27879410
TI  - Triple Staining Including FOXA2 Identifies Stem Cell Lineages Undergoing Hepatic
      and Biliary Differentiation in Cirrhotic Human Liver.
AB  - Recent investigations have reported many markers associated with human liver
      stem/progenitor cells, "oval cells," and identified "niches" in diseased livers
      where stem cells occur. However, there has remained a need to identify entire
      lineages of stem cells as they differentiate into bile ducts or hepatocytes. We
      have used combined immunohistochemical staining for a marker of hepatic
      commitment and specification (FOXA2 [Forkhead box A2]), hepatocyte maturation
      (Albumin and HepPar1), and features of bile ducts (CK19 [cytokeratin 19]) to
      identify lineages of stem cells differentiating toward the hepatocytic or bile
      ductular compartments of end-stage cirrhotic human liver. We identified large
      clusters of disorganized, FOXA2 expressing, oval cells in localized liver regions
      surrounded by fibrotic matrix, designated as "micro-niches." Specific FOXA2
      positive cells within the micro-niches organize into primitive duct structures
      that support both hepatocytic and bile ductular differentiation enabling
      identification of entire lineages of cells forming the two types of structures.
      We also detected expression of hsa-miR-122 in primitive ductular reactions
      expected for hepatocytic differentiation and hsa-miR-23b cluster expression that
      drives liver cell fate decisions in cells undergoing lineage commitment. Our data
      establish the foundation for a mechanistic hypothesis on how stem cell lineages
      progress in specialized micro-niches in cirrhotic end-stage liver disease.

PMID- 27879414
TI  - Corrigendum.

PMID- 27879412
TI  - Modeling Individual Patient Preferences for Colorectal Cancer Screening Based on
      Their Tolerance for Complications Risk.
AB  - INTRODUCTION: Recommendations for colorectal cancer screening encourage patients
      to choose among various screening methods based on individual preferences for
      benefits, risks, screening frequency, and discomfort. We devised a model to
      illustrate how individuals with varying tolerance for screening complications
      risk might decide on their preferred screening strategy. METHODS: We developed a
      discrete-time Markov mathematical model that allowed hypothetical individuals to
      maximize expected lifetime utility by selecting screening method, start age, stop
      age, and frequency. Individuals could choose from stool-based testing every 1 to
      3 years, flexible sigmoidoscopy every 1 to 20 years with annual stool-based
      testing, colonoscopy every 1 to 20 years, or no screening. We compared the life
      expectancy gained from the chosen strategy with the life expectancy available
      from a benchmark strategy of decennial colonoscopy. RESULTS: For an individual at
      average risk of colorectal cancer who was risk neutral with respect to screening
      complications (and therefore was willing to undergo screening if it would
      actuarially increase life expectancy), the model predicted that he or she would
      choose colonoscopy every 10 years, from age 53 to 73 years, consistent with
      national guidelines. For a similar individual who was moderately averse to
      screening complications risk (and therefore required a greater increase in life
      expectancy to accept potential risks of colonoscopy), the model predicted that he
      or she would prefer flexible sigmoidoscopy every 12 years with annual stool-based
      testing, with 93% of the life expectancy benefit of decennial colonoscopy. For an
      individual with higher risk aversion, the model predicted that he or she would
      prefer 2 lifetime flexible sigmoidoscopies, 20 years apart, with 70% of the life
      expectancy benefit of decennial colonoscopy. CONCLUSION: Mathematical models may
      formalize how individuals with different risk attitudes choose between various
      guideline-recommended colorectal cancer screening strategies.

PMID- 27879413
TI  - Characteristics and Course of Heart Failure Stages A-B and Determinants of
      Progression - design and rationale of the STAAB cohort study.
AB  - Background Data from the general population on the natural course of heart
      failure is lacking. The objectives of the STAAB cohort study are to determine the
      prevalence of heart failure stages A-B in a representative sample of the general
      population and to prospectively investigate the progression from asymptomatic
      cardiac dysfunction into symptomatic heart failure. Here we present study design,
      participation rates and baseline characteristics of the first 1468 enrolled
      subjects. Methods A random sample of inhabitants from the city of Wurzburg
      stratified by age (30-79 years) and gender was drawn from the local registration
      office. Subjects receive invitation letters, while send-out batches are
      continuously adapted to response rates by age and gender. At baseline
      examination, data on echocardiographic cardiac function, comorbidities and
      preclinical cardiovascular phenotypes are collected. After 3-5 years, changes in
      cardiac function and occurrence of clinical events will be assessed in a follow
      up visit. Results Between December 2013 and April 2015, 4499 subjects were
      invited; of those, 1510 (34.6%) responded positively, and 1468 were examined
      (32.6%). Stratified recruitment was on-target while the participation rate was
      highest in subjects aged 60-69 years (38%). Hypertension (42%) and dyslipidaemia
      (37%) were the most commonly reported comorbidities; 7% reported on diabetes and
      23% of men ( vs. 17% of women) were smokers. Conclusions STAAB recruits a
      representative population-based sample suited to provide reliable estimates of
      the frequency of asymptomatic cardiac dysfunction and determinants of disease
      progression into symptomatic heart failure. These findings will build the ground
      for developing preventive strategies for heart failure at different stages of the
      disease continuum.

PMID- 27879415
TI  - The angiotensin-converting enzyme inhibitor captopril rescues mice from endotoxin
      induced lethal hepatitis.
AB  - The renin-angiotensin system is classically regarded as a crucial regulator of
      circulatory homeostasis, but recent studies also revealed its pro-inflammatory
      roles. The beneficial effects of the angiotensin-converting enzyme inhibitor
      (ACEI) in severe inflammatory injury in the lung and heart have been previously
      reported, but its potential effects on lethal hepatitis were unknown. In this
      study, a mouse model with LPS/d-galactosamine (GalN)-induced fulminant hepatitis
      were used to test the protective potential of captopril, a representative ACEI.
      The results indicated that treatment with captopril significantly decreased the
      plasma level of alanine aminotransferase and aspartate aminotransferase,
      alleviated the histopathological damage of the liver tissue and improve the
      survival rate of LPS/GalN-challenged mice. These effects were accompanied by
      reduced mRNA levels of TNF-alpha and IL-6 in the liver, and decreased protein
      level of TNF-alpha and IL-6 in the plasma. In addition, the activation of
      caspases 3, 8 and 9, and the presence of TUNEL-positive apoptotic cells, were
      also suppressed by captopril treatment. The above evidence suggested that the
      renin-angiotensin system might be involved in the development of LPS/GalN-induced
      fulminant hepatitis and ACEI might have potential value in lethal hepatitis.

PMID- 27879416
TI  - Occupational pesticide exposure and respiratory health: a large-scale cross
      sectional study in three commercial farming systems in Ethiopia.
AB  - RATIONALE: In the last decade, due to expansion of greenhouses and irrigated
      farms, the use of pesticides in Ethiopia has increased 6-13-fold leading to
      potential health risks. OBJECTIVE: To investigate if occupational exposure to
      pesticides is associated with respiratory health effects in farmers and farm
      workers from commercial farming systems. METHODS: We performed two cross
      sectional surveys comprising different farming systems. In the first survey we
      studied respiratory symptoms among 1104 subjects of which 601 were occupationally
      exposed to pesticides (ie, 256 pesticide applicators, 345 re-entry workers) and
      503 unexposed individuals. The second survey, carried out 2 years later in the
      same farming regions, additionally included lung function measurement and
      comprised a total of 387 study subjects of which 206 were occupationally exposed
      to pesticides (142 applicators and 64 re-entry workers) and 180 unexposed
      individuals. RESULTS: We observed increased risks for chronic cough and shortness
      of breath (OR=3.15, 95% CI 1.56 to 6.36 and OR=6.67, 95% CI 2.60 to 17.58) among
      the exposed subjects as compared with unexposed individuals in the first survey.
      These results were corroborated in the second survey where we also observed
      reductions in FEV1 (140 mL), forced expiratory flow 25%-75% (550 mL/s) and risk
      of FEV1/FVC ratio <0.8 (OR=4.31, 95% CI 2.11 to 8.81) among pesticide exposed
      workers. CONCLUSIONS: These findings indicate an increased risk of adverse
      respiratory health among workers exposed to pesticides. As those effects occurred
      in young workers (mean age 27 years) and within a relative short duration of
      exposure (4 years) implementation of stringent occupational health measures are
      warranted.

PMID- 27879418
TI  - Histopathologic Effects of Onabotulinum Toxin A Treatment in Pediatric
      Submandibular Glands.
AB  - Onabotulinum toxin A (OBTXA) is an effective treatment for drooling. Our
      objective was to determine if there are histologic changes in the submandibular
      glands (SMGs) after repetitive OBTXA injections. The study included blinded
      histologic analysis and comparison of SMGs with >=4 OBTXA injections versus
      controls who never received OBTXA. The number of acinar cells were counted, and
      the morphology of the cells was evaluated within each histologic sample of the
      SMGs. Thirty-one glands were analyzed (14 control, 17 cases). No physical
      differences were observed between the 2 acinar cell groups. There was no
      significant difference in the number acinar cells per surface area in the control
      group as compared with the OBTXA group (1.29 +/- 0.13 vs 1.17 +/- 0.11
      cells/MUm2, respectively). To conclude, no significant histologic findings were
      established in this first human study on SMGs post-OBTXA treatment.

PMID- 27879417
TI  - Factors Influencing Likelihood of Voice Therapy Attendance.
AB  - Objective To identify factors associated with the likelihood of attending voice
      therapy among patients referred for it in the CHEER (Creating Healthcare
      Excellence through Education and Research) practice-based research network
      infrastructure. Study Design Prospectively enrolled cross-sectional study.
      Setting CHEER network of community and academic sites. Methods Data were
      collected on patient-reported demographics, voice-related diagnoses, voice
      related handicap (Voice Handicap Index-10), likelihood of attending voice therapy
      (VT), and opinions on factors influencing likelihood of attending VT. The
      relationships between patient characteristics/opinions and likelihood of
      attending VT were investigated. Results A total of 170 patients with various
      voice-related diagnoses reported receiving a recommendation for VT. Of those, 85%
      indicated that they were likely to attend it, regardless of voice-related
      handicap severity. The most common factors influencing likelihood of VT
      attendance were insurance/copay, relief that it was not cancer, and travel. Those
      who were not likely to attend VT identified, as important factors, unclear
      potential improvement, not understanding the purpose of therapy, and concern that
      it would be too hard. In multivariate analysis, factors associated with greater
      likelihood of attending VT included shorter travel distance, age (40-59 years),
      and being seen in an academic practice. Conclusions Most patients reported plans
      to attend VT as recommended. Patients who intended to attend VT reported
      different considerations in their decision making from those who did not plan to
      attend. These findings may inform patient counseling and efforts to increase
      access to voice care.

PMID- 27879419
TI  - Tympanoplasty Outcomes for Blast-Induced Perforations from Iraq and Afghanistan.
AB  - Objective To describe characteristics of blast-induced tympanic membrane
      perforations that do not spontaneously heal, evaluate the outcomes of
      tympanoplasty techniques, and understand the factors associated with surgical
      success. Setting Two tertiary military health care institutions. Study Design
      Case series with chart review. Subjects and Methods This study reviewed the
      practice of 1 military neurotologist and included all tympanoplasties for combat
      blast-induced perforations from 2007 to 2012, which comprised a total of 55
      patients. Surgical outcomes and associated perioperative factors were examined to
      include size, location, bilateral involvement, timing of surgery, and surgical
      technique. Results Fifty-five patients (68 ears) met inclusion criteria. Thirty
      six (53%) were total or near-total perforations, and 51% of patients had
      bilateral perforations. The overall success rate was 77%. It was 82% for lateral
      grafts and 70% for medial grafts, but the difference between these was not
      statistically significant. Age was a significant factor, with a success rate of
      56% for ages 25 to 34 years, compared with 90% for 20 to 24 and >34 years.
      Patients who had bilateral sequential tympanoplasties also had lower success
      rates than those who had only unilateral surgery (62% vs 87%, P = .002).
      Ossicular disruptions were found in 5 ears, and cholesteatoma was discovered in
      8. Surgical timing did not predict success, as the average time until repair was
      153 days in successful cases and 151 days in failures. The mean conductive
      hearing improvement was 13.6 dB, and there were no major complications.
      Conclusion Tympanoplasty can be challenging in this population. Age and bilateral
      surgery were the only independent variables that showed significance.

PMID- 27879422
TI  - A New Definition for Oral Health: Implications for Clinical Practice, Policy, and
      Research

PMID- 27879423
TI  - Structure and Profiles of Basic Motor Competencies in the Third Grade-Validation
      of the Test Instrument MOBAK-3.
AB  - Basic motor competencies are defined as motor performance dispositions that
      evolve from specific requirements in sports and exercise. After validating the
      MOBAK-1 instrument for first graders, we developed the MOBAK-3 for the assessment
      of basic motor competencies in third graders. We investigated the factorial and
      diagnostic validity of this instrument in a sample of 323 children (age: M = 9.2
      years, SD = .39; sex: boys, n = 158, girls, n = 165). A confirmatory factor
      analysis verified the theoretical structure with the two factors Locomotion and
      Object Control. By means of latent class analysis, we identified five latent
      classes that were connected with external criteria. We concluded that the MOBAK-3
      effectively evaluates the basic motor competencies of 8- to 10-year-old students.

PMID- 27879421
TI  - Loss of Notch3 Signaling Enhances Osteogenesis of Mesenchymal Stem Cells from
      Mandibular Torus.
AB  - Mandibular torus (MT) is a common intraoral osseous outgrowth located on the
      lingual surface of the mandible. Histologic features include hyperplastic bone
      consisting of mature cortical and trabecular bone. Some theories on the etiology
      of MT have been postulated, such as genetic factors, masticatory hyperfunction,
      trauma, and continued growth, but the underlying mechanism remains largely
      unknown. In this study, we investigated the potential role of mesenchymal stem
      cells (MSCs) derived from human MT in the pathogenesis of bone outgrowth. We
      demonstrated that MT harbored a distinct subpopulation of MSCs, with enhanced
      osteogenic and decreased adipogenic differentiation capacities, as compared with
      their counterparts from normal jaw bone. The increased osteogenic differentiation
      of mandibular torus MSCs was associated with the suppression of Notch3 signaling
      and its downstream target genes, Jag1 and Hey1, and a reciprocal increase in the
      transcriptional activation of ATF4 and NFATc1 genes. Targeted knockdown of Notch3
      expression by transient siRNA transfection promoted the expression of osteogenic
      transcription factors in normal jaw bone MSCs. Our data suggest that the loss of
      Notch3 signaling may contribute partly to bone outgrowth in MT, as mediated by
      enhanced MSC-driven osteogenic differentiation in the jaw bone.

PMID- 27879420
TI  - Saliva and Serum Protein Exchange at the Tooth Enamel Surface.
AB  - The acquired enamel pellicle is an oral, fluid-derived protein layer that forms
      on the tooth surface. It is a biologically and clinically important integument
      that protects teeth against enamel demineralization, and abrasion. Tooth surfaces
      are exposed to different proteinaceous microenvironments depending on the enamel
      location. For instance, tooth surfaces close to the gingival sulcus contact serum
      proteins that emanate via this sulcus, which may impact pellicle composition
      locally. The aims of this study were to define the major salivary and serum
      components that adsorb to hydroxyapatite, to study competition among them, and to
      obtain preliminary evidence in an in vivo saliva/serum pellicle model.
      Hydroxyapatite powder was incubated with saliva and serum, and the proteins that
      adsorbed were identified by mass spectrometry. To study competition, saliva and
      serum proteins were labeled with CyDyes, mixed in various proportions, and
      incubated with hydroxyapatite. In vivo competition was assessed using a split
      mouth design, with half the buccal tooth surfaces coated with serum and the other
      half with saliva. After exposure to the oral environment for 0 min, 30 min and 2
      h, the pellicles were analyzed by SDS-PAGE. In pure saliva- or serum-derived
      pellicles, 82 and 84 proteins were identified, respectively. When present
      concomitantly, salivary protein adsorbers effectively competed with serum protein
      adsorbers for the hydroxyapatite surface. Specifically, acidic proline-rich
      protein, cystatin, statherin and protein S100-A9 proteins competed off
      apolipoproteins, complement C4-A, haptoglobin, transthyretin and serotransferrin.
      In vivo evidence further supported the replacement of serum proteins by salivary
      proteins. In conclusion, although significant numbers of serum proteins emanate
      from the gingival sulcus, their ability to participate in dental pellicle
      formation is likely reduced in the presence of strong salivary protein adsorbers.
      The functional properties of the acquired enamel pellicle will therefore be
      mostly dictated by the salivary component.

PMID- 27879424
TI  - A Research Note on Challenges of Cross-National Aging Research: An Example of
      Productive Activities Across Three Countries.
AB  - Cross-national studies can elucidate the influence of sociocultural contexts on a
      wide variety of aging issues. This study aims to develop methods for using
      secondary data for cross-national comparisons using productive activities as an
      example. The study also identifies challenges in conducting cross-national
      research. Using the national representative data from the United States, China,
      and South Korea, this study developed a sequence of methods for cross-national
      analysis. Results indicate that productive activities vary by country, and this
      variation could possibly be due to the differences in sociocultural context and
      variations in operationalization and measurement. Given the difficulty of making
      decisions and drawing conclusions across different cultural contexts, team
      members must include scholars who are familiar with the culture and language of
      the region of study. Researchers also need to determine whether data sets are
      valid for cross-national comparisons and understand the limitations of the
      comparisons, given constraints in the data.

PMID- 27879426
TI  - The successful concurrent use of two long-acting depot antipsychotics in a
      patient with treatment-resistant schizophrenia and history of serious violence: a
      case report.
AB  - OBJECTIVE: This case report describes a forensic psychiatric patient presenting
      with treatment-resistant schizophrenia and serious interpersonal violence
      complicated by poor adherence to oral medication who was treated successfully
      with two concurrent long-acting depot antipsychotics. METHOD: Treatment response
      was measured for a 6-month period at 6-weekly intervals, post-initiation using
      the Positive and Negative Symptoms of Schizophrenia with Excited Component score
      (PANSS-EC), Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression
      Scale (CGI). RESULTS: At 6 months, the presentation was found to have markedly
      improved. The overall PANSS-EC score was reduced by 43.9%, with reductions in
      Positive Symptom and Excited Component subscales most evident. BPRS Score was
      reduced from 81 at baseline to 47 at 18 weeks. There was improvement in the
      patient's level of cooperativeness, aggression and engagement in ward therapeutic
      activities. CONCLUSION: Although concurrent use of two depot antipsychotics
      requires further exploration, there is potential benefit for patient groups
      presenting with treatment-resistant schizophrenia and poor compliance. Due to
      risk of serious adverse effects which are difficult to reverse with long-acting
      formulations, we recommend this option be reserved for this complex patient
      population and exclusively in care settings allowing close physical health
      monitoring.

PMID- 27879427
TI  - Abnormality in hippocampal signal intensity predicts atrophy in patients with
      systemic lupus erythematosus.
AB  - Objectives To quantify signal abnormalities in the hippocampus (Hsig) of patients
      with systemic lupus erythematosus (SLE) and to determine if Hsig predict
      hippocampal atrophy (HA) in SLE. Methods We included all SLE patients and healthy
      age- and sex-matched individuals with two magnetic resonance imaging (MRI) scans
      performed with a minimum of 1 year interval. All individuals underwent a
      standardized neuropsychological evaluation. Individual results were converted
      into standard scores and compared to normative data. SLE patients were
      additionally assessed for disease activity (SLE Disease Activity Index (SLEDAI)),
      damage (Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology Damage Index (SDI)), and the presence of antiphospholipid
      antibodies. MRI was performed on an Elscint 2 T scanner and T1 inversion recovery
      and T2 coronal images were used for analysis. Volumetric (HV) and signal
      quantification (Hsig) were determined by standardized protocols. Results We
      included 54 SLE patients (48 women; mean age 32.2 +/- 10.56 years). Hsig were
      found at study entry in 15 (45.5%) patients. Hsig in the body and tail of non
      atrophic hippocampi correlated with progression of volume loss during the follow
      up period ( r = 0.8, p < 0.001). The presence of Hsig in the head of atrophic
      hippocampi correlated with progression of HA ( r = 0.73, p = 0.005) during the
      same period. No correlation of Hsig and disease activity or prednisone dose was
      observed. Conclusion HA is frequently observed in SLE patients and volume loss is
      progressive in a subgroup of patients. The evaluation of Hsig is an easy tool to
      determine patients that may have progressive hippocampal volume loss and should
      be followed more closely with MRI and cognitive evaluation.

PMID- 27879425
TI  - Clinical teaching and supervision in postgraduate psychiatry training: the
      trainee perspective.
AB  - OBJECTIVE: We aimed to explore psychiatry trainees' perspectives on clinical
      teaching and supervision as well as how this might be improved. METHOD: New
      Zealand trainees ( n=51) completed online the Maastricht Clinical Teaching
      Questionnaire (MCQT) and three open-ended questions. RESULTS: The majority rated
      'agree' or 'strongly agree' to all items of the MCQT. Weaknesses in the feedback
      process including observation, feedback provision, and formulating learning goals
      were highlighted. College training requirements and workplace environment were
      identified as factors impacting on clinical teaching and supervision.
      CONCLUSIONS: A model was proposed to enhance awareness of the various factors
      involved in the feedback process.

PMID- 27879428
TI  - A polymorphism upstream MIR1279 gene is associated with pericarditis development
      in Systemic Lupus Erythematosus and contributes to definition of a genetic risk
      profile for this complication.
AB  - Recently, a study has shown that a polymorphism in the region of MIR1279
      modulates the expression of the TRAF3IP2 gene. Since polymorphisms in the
      TRAF3IP2 gene have been described in association with systemic lupus
      erithematosus (SLE) susceptibility and with the development of pericarditis, our
      aim is to verify if the MIR1279 gene variability could also be involved. The
      rs1463335 SNP, located upstream MIR1279 gene, was analyzed by allelic
      discrimination assay in 315 Italian SLE patients and 201 healthy controls.
      Moreover, the MIR1279 gene was full sequenced in 50 patients. A case/control
      association study and a genotype/phenotype correlation analysis were performed.
      We also constructed a pericarditis genetic risk profile for patients with SLE.
      The full sequencing of the MIR1279 gene in patients with SLE did not reveal any
      novel or known variation. The variant allele of the rs1463335 SNP was
      significantly associated with susceptibility to pericarditis ( P = 0.017 and OR =
      1.67). A risk profile model for pericarditis considering the risk alleles of
      MIR1279 and three other genes (STAT4, PTPN2 and TRAF3IP2) showed that patients
      with 4 or 5 risk alleles have a higher risk of developing pericarditis ( OR =
      4.09 with P = 0.001 and OR = 6.04 with P = 0.04 respectively). In conclusion, we
      describe for the first time the contribution of a MIR1279 SNP in pericarditis
      development in patients with SLE and a genetic risk profile model that could be
      useful to identify patients more susceptible to developing pericarditis in SLE.
      This approach could help to improve the prediction and the management of this
      complication.

PMID- 27879429
TI  - Is the Nation-state and Its Welfare State Dead? A Critique of Varoufakis.

PMID- 27879430
TI  - Factors that can influence feelings towards and interactions with people living
      with HIV/AIDS in rural Central Kenya.
AB  - Background In Kenya, HIV incidence and prevalence have declined. HIV rates are
      lower in rural areas than in urban areas. However, HIV infection is reported
      higher in men in rural areas (4.5%) compared to those in urban areas (3.7%).
      Objectives This study examined HIV knowledge, feelings, and interactions towards
      HIV-infected from 302 participants in rural Central Kenya. Methods Chi square
      tests and multivariable logistic regression analyzed variables of interest.
      Results Most participants exhibited positive feelings in their interaction with
      people living with HIV and AIDS (PLWHA). Association between HIV knowledge and
      socio-demographic characteristics revealed that the proportion of participants
      with a correct response differed by gender, age, level of education, and marital
      status ( p < 0.05). Compared to those with inadequate knowledge of HIV/AIDS,
      participants with adequate HIV/AIDS knowledge were nearly three times as likely
      to disagree that PLWHA should be legally separated from others to protect public
      health (adjusted odds ratio: aOR (95% CI) (2.76 (1.12, 6.80). Conclusions HIV
      stigma continues to impact HIV prevention strategies particularly in rural
      Central Kenya. Culturally, appropriate interventions addressing HIV knowledge
      among those with lower levels of education, single, older, and male are
      warranted. Review of HIV policies separating high-risk populations from the
      general population is needed to reduce stigma.

PMID- 27879431
TI  - Efficient in situ detection of mRNAs using the Chlorella virus DNA ligase for
      padlock probe ligation.
AB  - Padlock probes are single-stranded DNA molecules that are circularized upon
      hybridization to their target sequence by a DNA ligase. In the following, the
      circulated padlock probes are amplified and detected with fluorescently labeled
      probes complementary to the amplification product. The hallmark of padlock probe
      assays is a high detection specificity gained by the ligation reaction.
      Concomitantly, the ligation reaction is the largest drawback for a quantitative
      in situ detection of mRNAs due to the low affinities of common DNA or RNA ligases
      to RNA-DNA duplex strands. Therefore, current protocols require that mRNAs be
      reverse transcribed to DNA before detection with padlock probes. Recently, it was
      found that the DNA ligase from Paramecium bursaria Chlorella virus 1 (PBCV-1) is
      able to efficiently ligate RNA-splinted DNA. Hence, we designed a padlock probe
      assay for direct in situ detection of mRNAs using the PBCV-1 DNA ligase.
      Experimental single-cell data were used to optimize and characterize the
      efficiency of mRNA detection with padlock probes. Our results demonstrate that
      the PBCV-1 DNA ligase overcomes the efficiency limitation of current protocols
      for direct in situ mRNA detection, making the PBCV-1 DNA ligase an attractive
      tool to simplify in situ ligation sequencing applications.

PMID- 27879433
TI  - Comparison of SHAPE reagents for mapping RNA structures inside living cells.
AB  - Recent advances in SHAPE technology have converted the classic primer extension
      method to next-generation sequencing platforms, allowing transcriptome-level
      analysis of RNA secondary structure. In particular, icSHAPE and SHAPE-MaP, using
      NAI-N3 and 1M7 reagents, respectively, are methods that claim to measure in vivo
      structure with high-throughput sequencing. However, these compounds have not been
      compared on an unbiased, raw-signal level. Here, we directly compare several in
      vivo SHAPE acylation reagents using the simple primer extension assay. We
      conclude that while multiple SHAPE technologies are effective at measuring
      purified RNAs in vitro, acylimidazole reagents NAI and NAI-N3 give markedly
      greater signals with lower background than 1M7 for in vivo measurement of the RNA
      structurome.

PMID- 27879432
TI  - Induced fit of the peptidyl-transferase center of the ribosome and conformational
      freedom of the esterified amino acids.
AB  - The catalytic site of most enzymes can efficiently handle only one substrate. In
      contrast, the ribosome is capable of polymerizing at a similar rate at least 20
      different kinds of amino acids from aminoacyl-tRNA carriers while using just one
      catalytic site, the peptidyl-transferase center (PTC). An induced-fit mechanism
      has been uncovered in the PTC, but a possible connection between this mechanism
      and the uniform handling of the substrates has not been investigated. We present
      an analysis of published ribosome structures supporting the hypothesis that the
      induced fit eliminates unreactive rotamers predominantly populated for some A
      site aminoacyl esters before induction. We show that this hypothesis is fully
      consistent with the wealth of kinetic data obtained with these substrates. Our
      analysis reveals that induction constrains the amino acids into a reactive
      conformation in a side-chain independent manner. It allows us to highlight the
      rationale of the PTC structural organization, which confers to the ribosome the
      very unusual ability to handle large as well as small substrates.

PMID- 27879434
TI  - 5'-Terminal nucleotide variations in human cytoplasmic tRNAHisGUG and its 5'
      halves.
AB  - Transfer RNAs (tRNAs) are fundamental adapter components of translational
      machinery. tRNAs can further serve as a source of tRNA-derived noncoding RNAs
      that play important roles in various biological processes beyond translation.
      Among all species of tRNAs, tRNAHisGUG has been known to uniquely contain an
      additional guanosine residue at the -1 position (G-1) of its 5'-end. To analyze
      this -1 nucleotide in detail, we developed a TaqMan qRT-PCR method that can
      distinctively quantify human mature cytoplasmic tRNAHisGUG containing G-1, U-1, A
      1, or C-1 or lacking the -1 nucleotide (starting from G1). Application of this
      method to the mature tRNA fraction of BT-474 breast cancer cells revealed the
      presence of tRNAHisGUG containing U-1 as well as the one containing G-1 Moreover,
      tRNA lacking the -1 nucleotide was also detected, thus indicating the
      heterogeneous expression of 5'-tRNAHisGUG variants. A sequence library of sex
      hormone-induced 5'-tRNA halves (5'-SHOT-RNAs), identified via cP-RNA-seq of a BT
      474 small RNA fraction, also demonstrated the expression of 5'-tRNAHisGUG halves
      containing G-1, U-1, or G1 as 5'-terminal nucleotides. Although the detected 5'
      nucleotide species were identical, the relative abundances differed widely
      between mature tRNA and 5'-half from the same BT-474 cells. The majority of
      mature tRNAs contained the -1 nucleotide, whereas the majority of 5'-halves
      lacked this nucleotide, which was biochemically confirmed using a primer
      extension assay. These results reveal the novel identities of tRNAHisGUG
      molecules and provide insights into tRNAHisGUG maturation and the regulation of
      tRNA half production.

PMID- 27879436
TI  - Cytological Bone Marrow Cell Differential Counts and Morphologic Findings in
      Healthy Cynomolgus Monkeys ( Macaca fascicularis) from Nonclinical Toxicology
      Studies.
AB  - Cytological bone marrow evaluation is utilized in nonclinical toxicology studies
      to characterize hematopoietic effects when the combined interpretation of
      histologic and complete blood count data does not yield sufficient information.
      Results from cytological bone marrow examination should be interpreted in the
      context of variability observed in concurrent control animals with consideration
      of cytologist experience and historical/published data. Cytological bone marrow
      differential counts and cellular morphologic findings from 130 (66 male, 64
      female) healthy control cynomolgus monkeys from nonclinical toxicology studies
      were retrospectively analyzed. Myeloid to erythroid (M:E) ratios and the
      percentage of total cells for each cell type were determined from differential
      cell count data. M:E ratios ranged from 0.6:1 to 2.3:1. Percentages of total
      granulocytic cells, total erythroid cells, and lymphocytes ranged from 26.6% to
      60.6%, 25.7% to 52.2%, and 5.5% to 40.4%, respectively. Monocytes, plasma cells,
      mast cells, and mitotic figures were typically <1% of total cells. Notable
      morphologic findings included occasional giant neutrophilic metamyelocytes and
      band neutrophils, ring-shaped band neutrophil nuclei, metarubricyte nuclear
      blebbing and binucleation, multiple or nonfused megakaryocyte nuclei, and
      emperipolesis. These results represent cytological bone marrow findings from
      healthy control cynomolgus monkeys utilized in nonclinical toxicology studies and
      provide insight into expected background variability.

PMID- 27879435
TI  - Identification of MHC Haplotypes Associated with Drug-induced Hypersensitivity
      Reactions in Cynomolgus Monkeys.
AB  - Drug-induced hypersensitivity reactions can significantly impact drug development
      and use. Studies to understand risk factors for drug-induced hypersensitivity
      reactions have identified genetic association with specific human leukocyte
      antigen (HLA) alleles. Interestingly, drug-induced hypersensitivity reactions can
      occur in nonhuman primates; however, association between drug-induced
      hypersensitivity reactions and major histocompatibility complex (MHC) alleles has
      not been described. In this study, tissue samples were collected from 62
      cynomolgus monkeys from preclinical studies in which 9 animals had evidence of
      drug-induced hypersensitivity reactions. Microsatellite analysis was used to
      determine MHC haplotypes for each animal. A total of 7 haplotypes and recombinant
      MHC haplotypes were observed, with distribution frequency comparable to known MHC
      I allele frequency in cynomolgus monkeys. Genetic association analysis identified
      alleles from the M3 haplotype of the MHC I B region (B*011:01, B*075:01,
      B*079:01, B*070:02, B*098:05, and B*165:01) to be significantly associated (chi2
      test for trend, p < 0.05) with occurrence of drug-induced hypersensitivity
      reactions. Sequence similarity from alignment of alleles in the M3 haplotype B
      region and HLA alleles associated with drug-induced hypersensitivity reactions in
      humans was 86% to 93%. These data demonstrate that MHC alleles in cynomolgus
      monkeys are associated with drug-induced hypersensitivity reactions, similar to
      HLA alleles in humans.

PMID- 27879438
TI  - A Comparison of Rodent and Nonrodent Laryngeal and Tracheal Bifurcation
      Sensitivities in Inhalation Toxicity Studies and Their Relevance for Human
      Exposure.
AB  - In inhalation toxicity studies, drug-induced lesions are frequently reported in
      the larynx and sometimes at the tracheal bifurcation (carina) in the rat, but
      less so in the dog or monkey, bringing into question the relevance of these
      rodent findings for humans. The rat larynx is widely considered to be more
      sensitive than that of the dog and monkey in its response to inhaled xenobiotics,
      although we could find no published data to support this. In this review, data
      from 52 inhalation studies involving rodent and nonrodent species were collated
      and reviewed. These data showed that the rodent larynx, and to a lesser extent
      the carina, was far more commonly affected by treatment than those of the
      nonrodent. This review indicates the greater susceptibility of the rodent larynx
      and carina and emphasizes their lack of relevance for man. Observations and data
      suggest that the human larynx is much closer to the beagle dog and cynomolgus
      monkey in its response to inhaled xenobiotics and that greater clinical relevance
      should be placed on any specific findings in these animal models.

PMID- 27879439
TI  - Interpreting and Integrating Clinical and Anatomic Pathology Results.
AB  - The continuing education course on integrating clinical and anatomical pathology
      data was designed to communicate the importance of using a weight of evidence
      approach to interpret safety findings in toxicology studies. This approach is
      necessary, as neither clinical nor anatomic pathology data can be relied upon in
      isolation to fully understand the relationship between study findings and the
      test article. Basic principles for correlating anatomic pathology and clinical
      pathology findings and for integrating these with other study end points were
      reviewed. To highlight these relationships, a series of case examples, presented
      jointly by a clinical pathologist and an anatomic pathologist, were used to
      illustrate the collaborative effort required between clinical and anatomical
      pathologists. In addition, the diagnostic utility of traditional liver biomarkers
      was discussed using results from a meta-analysis of rat hepatobiliary marker and
      histopathology data. This discussion also included examples of traditional and
      novel liver and renal biomarker data implementation in nonclinical toxicology
      studies to illustrate the relationship between discrete changes in biochemistry
      and tissue morphology.

PMID- 27879441
TI  - Amyloid A Amyloidosis.

PMID- 27879440
TI  - Utopian Hopes or Dystopian Fears? Exploring the Motivational Underpinnings of
      Moralized Political Engagement.
AB  - People are more likely to become politically engaged (e.g., vote, engage in
      activism) when issues are associated with strong moral convictions. The goal of
      this research was to understand the underlying motivations that lead to this well
      replicated effect. Specifically, to what extent is moralized political engagement
      motivated by proscriptive concerns (e.g., perceived harms, anticipated regret),
      prescriptive concerns (e.g., perceived benefits, anticipated pride), or some
      combination of these processes? And are the motivational pathways between moral
      conviction and political engagement the same or different for liberals and
      conservatives? Two studies (combined N = 2,069) found that regardless of
      political orientation, the association between moral conviction and political
      engagement was mediated by the perceived benefits of preferred but not the
      perceived harms of non-preferred policy outcomes, and by both anticipated pride
      and regret, findings that replicated in two contexts: legalizing same-sex
      marriage and allowing concealed weapons on college campuses.

PMID- 27879442
TI  - Salmonella Enterica Serovar Pomona Infection in Farmed Juvenile American
      Alligators ( Alligator Mississippiensis).
AB  - A fatal epizootic of salmonellosis occurred in farmed juvenile American
      alligators in Louisiana. Six animals were examined. Gross lesions included severe
      fibrinonecrotizing enterocolitis, necrotizing splenitis, coelomic effusion, and
      perivisceral and pulmonary edema. Microscopic examination revealed severe
      necrotizing enterocolitis and splenitis with intralesional bacteria and
      pneumocyte necrosis with fibrin thrombi. Salmonella enterica serovar Pomona was
      isolated from intestine and lung. Clinical salmonellosis is a rare finding in
      reptiles and salmonellosis caused by S. Pomona is not previously reported in
      American alligators. Since S. Pomona is a commonly isolated Salmonella serotype
      from patients with reptile-associated salmonellosis in the United States, and
      since alligator meat is consumed and the skin is exported to numerous countries,
      risk of human and animal infection should be considered.

PMID- 27879443
TI  - Skeletal Metastasis of Canine Urothelial Carcinoma: Pathologic and Computed
      Tomographic Features.
AB  - Invasive urothelial (transitional cell) carcinoma (UC) is the most common cancer
      in the canine urinary tract. Prolonged survival of dogs with UC due to better
      management of the primary tumor and prevention of urethral obstruction might have
      contributed to an apparent increase in distant metastasis. Metastasis to bone is
      particularly concerning because the ensuing pain often leads to euthanasia;
      however, little is known of the frequency, site, or nature of UC skeletal
      metastasis. In a retrospective analysis, 17 (9%) of 188 canine UC cases had
      histologically confirmed skeletal metastasis, mainly to the vertebrae. In a
      prospective analysis of 21 dogs with UC that underwent total body computed
      tomography (CT) at euthanasia followed by a standardized pathologic examination,
      skeletal lesions detected on CT were suspected to be metastatic in 4 dogs and
      were confirmed as metastatic UC histologically in 3 (14%) dogs. In all 3 cases,
      skeletal metastasis had been suspected based on history and physical examination;
      however, 1 dog had additional CT-detected skeletal metastases in a clinically
      unsuspected location, and 2 dogs had histologically confirmed skeletal metastases
      that corresponded to nonspecific osseous lesions on CT. These findings suggest
      that total body CT could be helpful in detecting skeletal metastasis as a cause
      of bone pain in dogs with UC as well as in identifying clinically "silent" sites
      of skeletal metastasis.

PMID- 27879444
TI  - Histologic and Immunohistochemical Analyses of Soft Tissue Sarcomas From brca2
      Mutant/ tp53-Mutant Zebrafish Are Consistent With Neural Crest (Schwann Cell)
      Origin.
AB  - The zebrafish ( Danio rerio) provides a powerful model for analyzing genetic
      contributors to cancer. Multiple zebrafish lines with cancer-associated genetic
      mutations develop soft tissue sarcomas that are histologically consistent with
      malignant peripheral nerve sheath tumor (MPNST). The goal of this study was to
      determine the phenotype of soft tissue sarcomas in a brca2-mutant/ tp53-mutant
      zebrafish line using immunohistochemical markers that are commonly expressed in
      mammalian MPNST. We classified 70 soft tissue sarcomas from a brca2-mutant/ tp53
      mutant zebrafish cohort as MPNST, undifferentiated sarcoma, or other tumor based
      on histologic features. The expression of S100, CD57, and glial fibrillary acidic
      protein (GFAP) was analyzed in nonneoplastic neural tissues and tumor specimens
      by immunohistochemistry. Each marker was expressed in nonneoplastic neural
      tissues. In MPNST, S100 and CD57 were widely expressed in neoplastic cells, with
      greater consistency observed for CD57 expression. In undifferentiated sarcomas,
      results were variable and correlated to anatomic location. Coelomic
      undifferentiated sarcomas often exhibited widespread CD57 expression but limited
      S100 expression. In comparison, ocular undifferentiated sarcomas exhibited
      limited expression of both CD57 and S100. Overall, CD57 and S100 expression was
      significantly higher in MPNST than in undifferentiated sarcomas. GFAP was not
      expressed in any of the tumors. This study identified commercially available
      antibodies that are useful for analyzing S100, CD57, and GFAP expression in
      zebrafish. This study further shows a correlation between degree of histologic
      differentiation and expression of these markers in soft tissue sarcomas from
      brca2-mutant/ tp53-mutant zebrafish and suggests that these cancers are derived
      from the neural crest with differentiation toward myelinating Schwann cells.

PMID- 27879445
TI  - Agreement Among Stroke Faculty and Fellows in Treating Ischemic Stroke Patients
      With Tissue-Type Plasminogen Activator and Thrombectomy.
AB  - BACKGROUND AND PURPOSE: The aim of this study is to determine agreement among
      vascular neurology fellows and faculty in treating patients with acute ischemic
      stroke with intravenous tissue-type plasminogen activator and intra-arterial
      thrombectomy (IAT). METHODS: Patients were evaluated simultaneously by at least 2
      vascular neurology. Agreement was determined using kappa (kappa) and intraclass
      correlation coefficients. RESULTS: In 60 patients, agreement was substantial for
      tissue-type plasminogen activator (kappa=0.75 [95% confidence interval, 0.57
      0.92]) and IAT (kappa=0.63 [95% confidence interval, 0.30-0.96]), with no
      difference between fellow-fellow versus fellow-faculty. Intraclass correlation
      coefficient for National Institutes of Health Stroke Scale was 0.94 (95%
      confidence interval, 0.90-0.97) and kappa for Alberta Stroke Program Early CT
      Score was 0.53 (95% confidence interval, 0.20-0.78). Rapidly improving or mild
      deficits caused disagreement for both tissue-type plasminogen activator and IAT,
      whereas interpretation of computed tomographic perfusion led to disagreement for
      IAT. CONCLUSIONS: We found substantial agreement between vascular neurology
      fellows and faculty in treating with tissue-type plasminogen activator or IAT.
      Areas for improvement include recognition of stroke mimics, consensus on treating
      less severe strokes, and use/interpretation of imaging.

PMID- 27879446
TI  - Quantification of Serial Cerebral Blood Flow in Acute Stroke Using Arterial Spin
      Labeling.
AB  - BACKGROUND AND PURPOSE: Perfusion-weighted imaging is used to select patients
      with acute ischemic stroke for intervention, but knowledge of cerebral perfusion
      can also inform the understanding of ischemic injury. Arterial spin labeling
      allows repeated measurement of absolute cerebral blood flow (CBF) without the
      need for exogenous contrast. The aim of this study was to explore the
      relationship between dynamic CBF and tissue outcome in the month after stroke
      onset. METHODS: Patients with nonlacunar ischemic stroke underwent <=5 repeated
      magnetic resonance imaging scans at presentation, 2 hours, 1 day, 1 week, and 1
      month. Imaging included vessel-encoded pseudocontinuous arterial spin labeling
      using multiple postlabeling delays to quantify CBF in gray matter regions of
      interest. Receiver-operator characteristic curves were used to predict tissue
      outcome using CBF. Repeatability was assessed in 6 healthy volunteers and
      compared with contralateral regions of patients. Diffusion-weighted and T2
      weighted fluid attenuated inversion recovery imaging were used to define tissue
      outcome. RESULTS: Forty patients were included. In contralateral regions of
      patients, there was significant variation of CBF between individuals, but not
      between scan times (mean+/-SD: 53+/-42 mL/100 g/min). Within ischemic regions,
      mean CBF was lowest in ischemic core (17+/-23 mL/100 g/min), followed by regions
      of early (21+/-26 mL/100 g/min) and late infarct growth (25+/-35 mL/100 g/min;
      ANOVA P<0.0001). Between patients, there was marked overlap in presenting and
      serial CBF values. CONCLUSIONS: Knowledge of perfusion dynamics partially
      explained tissue fate. Factors such as metabolism and tissue susceptibility are
      also likely to influence tissue outcome.

PMID- 27879447
TI  - Computed Tomographic Blend Sign Is Associated With Computed Tomographic
      Angiography Spot Sign and Predicts Secondary Neurological Deterioration After
      Intracerebral Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Significant early hematoma growth in patients with
      intracerebral hemorrhage is an independent predictor of poor functional outcome.
      Recently, the novel blend sign (BS) has been introduced as a new imaging sign for
      predicting hematoma growth in noncontrast computed tomography. Another parameter
      predicting increasing hematoma size is the well-established spot sign (SS)
      visible in computed tomographic angiography. We, therefore, aimed to clarify the
      association between established SS and novel BS and their values predicting a
      secondary neurological deterioration. METHODS: Retrospective study inclusion
      criteria were (1) spontaneous intracerebral hemorrhage confirmed on noncontrast
      computed tomography and (2) noncontrast computed tomography and computed
      tomographic angiography performed on admission within 6 hours after onset of
      symptoms. We defined a binary outcome (secondary neurological deterioration
      versus no secondary deterioration). As secondary neurological deterioration, we
      defined (1) early hemicraniectomy under standardized criteria or (2) secondary
      decrease of Glasgow Coma Scale of >3 points, both within the first 48 hours after
      symptom onset. RESULTS: Of 182 patients with spontaneous intracerebral
      hemorrhage, 37 (20.3%) presented with BS and 39 (21.4%) with SS. Of the 81
      patients with secondary deterioration, 31 (38.3%) had BS and SS on admission.
      Multivariable logistic regression analysis identified hematoma volume (odds
      ratio, 1.07 per mL; P<=0.001), intraventricular hemorrhage (odds ratio, 3.08;
      P=0.008), and the presence of BS (odds ratio, 11.47; P<=0.001) as independent
      predictors of neurological deterioration. CONCLUSIONS: The BS, which is
      obtainable in noncontrast computed tomography, shows a high correlation with the
      computed tomographic angiography SS and is a reliable predictor of secondary
      neurological deterioration after spontaneous intracerebral hemorrhage.

PMID- 27879450
TI  - Human Placental Arterial Distensibility, Birth Weight, and Body Size Are
      Positively Related to Fetal Homocysteine Concentration.
AB  - Methionine demethylation during metabolism generates homocysteine (Hcy) and its
      remethylation requires folate and cobalamin. Elevated Hcy concentrations are
      associated with vascular-related complications of pregnancy, including increased
      vascular stiffness, predictive of clinical vascular disease. Maternal and fetal
      total Hcy (tHcy) concentrations are positively related, yet the influence of Hcy
      on fetoplacental vascular function in normal pregnancy has not been examined. We
      hypothesized that Hcy alters fetoplacental vascular characteristics with
      influences on fetal growth outcomes. We investigated (1) placental chorionic
      plate artery distensibility and neonatal blood pressure in relation to umbilical
      plasma tHcy; (2) relationships between cord venous (CV) and cord arterial (CA)
      plasma tHcy, folate, and cobalamin concentrations; and (3) tHcy associations with
      birth weight and anthropometric measurements of body size as indices of fetal
      growth in normal pregnancies with appropriate weight-for-gestational age
      newborns. Maternal plasma tHcy, folate, and cobalamin concentrations were
      consistent with published data. Placental chorionic plate artery distensibility
      index (beta; measure of vessel stiffness) was inversely related to CA tHcy, yet
      neonatal blood pressure was not significantly affected. CV and CA tHcy
      concentrations were positively related and CV tHcy negatively related to CV
      cobalamin but not folate. CV tHcy concentration positively related to birth
      weight, corrected birth weight percentile, length, head circumference, and mid
      arm circumference of newborns. CV cobalamin was inversely related to fetal growth
      indices but not to folate concentration. Our study demonstrates a potential
      relationship between fetal tHcy and placental artery distensibility, placing
      clinical relevance to cobalamin in influencing Hcy concentration and maintaining
      low vascular resistance to facilitate nutrient exchange favorable to fetal
      growth.

PMID- 27879448
TI  - RhoA Kinase Inhibition With Fasudil Versus Simvastatin in Murine Models of
      Cerebral Cavernous Malformations.
AB  - BACKGROUND AND PURPOSE: We sought to compare the effect of chronic treatment with
      commonly tolerated doses of Fasudil, a specific RhoA kinase (ROCK) inhibitor, and
      simvastatin (with pleiotropic effects including ROCK inhibition) on cerebral
      cavernous malformation (CCM) genesis and maturation in 2 models that recapitulate
      the human disease. METHODS: Two heterozygous murine models, Ccm1+/-Msh2-/- and
      Ccm2+/-Trp53-/-, were treated from weaning to 4 to 5 months of age with Fasudil
      (100 mg/kg per day), simvastatin (40 mg/kg per day) or with placebo. Mouse brains
      were blindly assessed for CCM lesion burden, nonheme iron deposition (as a
      quantitative measure of chronic lesional hemorrhage), and ROCK activity. RESULTS:
      Fasudil, but not simvastatin, significantly decreased mature CCM lesion burden in
      Ccm1+/-Msh2-/- mice, and in meta-analysis of both models combined, when compared
      with mice receiving placebo. Fasudil and simvastatin both significantly decreased
      the integrated iron density per mature lesion area in Ccm1+/-Msh2-/- mice, and in
      both models combined, compared with mice given placebo. ROCK activity in mature
      lesions of Ccm1+/-Msh2-/- mice was similar with both treatments. Fasudil, but not
      simvastatin, improved survival in Ccm1+/-Msh2-/- mice. Fasudil and simvastatin
      treatment did not affect survival or lesion development significantly in Ccm2+/
      Trp53-/- mice alone, and Fasudil benefit seemed limited to males. CONCLUSIONS:
      ROCK inhibitor Fasudil was more efficacious than simvastatin in improving
      survival and blunting the development of mature CCM lesions. Both drugs
      significantly decreased chronic hemorrhage in CCM lesions. These findings justify
      the development of ROCK inhibitors and the clinical testing of commonly used
      statin agents in CCM.

PMID- 27879449
TI  - Ethnic Comparison of Clinical Characteristics and Ischemic Stroke Subtypes Among
      Young Adult Patients With Stroke in Hawaii.
AB  - BACKGROUND AND PURPOSE: Native Hawaiians and other Pacific Islanders (NHOPI) with
      ischemic stroke have younger age of stroke onset compared with whites. However,
      ethnic differences in stroke subtypes in this population have been inadequately
      studied. METHODS: Consecutive young adult patients (aged <=55 years) who were
      hospitalized for ischemic stroke between 2006 and 2012 at a tertiary center in
      Honolulu were studied. Clinical characteristics and stroke subtypes based on
      pathophysiological TOAST classification (Trial of Org 10172) of NHOPI and Asians
      were compared with whites. RESULTS: A total of 427 consecutive young adult (mean
      age, 46.7+/-7.8 years) patients (NHOPI 45%, Asians 38%, and whites 17%) were
      studied. NHOPI had a higher prevalence of hypertension, diabetes mellitus,
      prosthetic valve, higher body mass index, hemoglobin A1c, and lower high-density
      lipoprotein than whites (all P<0.05). Stroke subtype distribution was not
      different between the ethnic groups. Specifically, the prevalence of small-vessel
      disease was similar between NHOPI (26.6%), whites (28.4%), and Asians (24.8%). In
      the univariate analyses, the use of intravenous tissue-type plasminogen activator
      was lower among NHOPI (4.7%; P=0.01) and Asians (3.1%; P=0.002) than among whites
      (12.5%). In the multivariable model, NHOPI (odds ratio, 0.35; 95% confidence
      interval, 0.12-0.98) and Asians (odds ratio, 0.23; 95% confidence interval, 0.07
      0.74) were less likely to be treated with intravenous tissue-type plasminogen
      activator than whites. CONCLUSIONS: NHOPI have greater cardiovascular risk
      factors than whites, but there were no differences in stroke subtypes between the
      ethnic groups. Furthermore, NHOPI and Asians may be less likely to be treated
      with intravenous tissue-type plasminogen activator than whites.

PMID- 27879451
TI  - Tetraspanins and Mouse Oocyte Microvilli Related to Fertilizing Ability.
AB  - Our electron microscopy observations demonstrate for the first time that the
      number of microvilli on the mice oocyte membrane decreases when meiosis
      progresses from prophase I to metaphase II (MII) stage, and the morphology of the
      microvilli also changes. Microvilli are significantly shorter and larger on the
      ovulated oocyte membrane than at the previous stages. Although clathrin vesicles
      clearly disappear during oocyte maturation, exosome-like vesicles begin to be
      secreted at the metaphase I stage, more strongly at the MII stage. Multivesicular
      bodies are visible only at the MII stage. Since several oocyte tetraspanins are
      involved in the gamete interaction, Cd9 being congregated on the MII oocyte
      microvilli, we analyzed the effect of tetraspanin deletion on oocyte membrane
      morphology. The Cd9-/- and Cd9-/- Cd81-/- deletions are associated with a
      decreased microvilli density on the MII oocyte surface. Microvilli thickness is
      significantly increased whatever the deleted tetraspanin gene be. Only Cd9
      deletion clearly disturbs the vesicular traffic, increasing the number of
      clathrin and exosome vesicles. Additional investigations are necessary to
      elucidate how tetraspanins modulate the microvilli morphology, likely in relation
      with cytoskeleton. The role of oocyte exosomes in gamete adhesion/fusion remains
      to be further studied.

PMID- 27879452
TI  - Umbilical Cord Blood Circulating Progenitor Cells and Endothelial Colony-Forming
      Cells Are Decreased in Preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy-specific disease characterized by the new onset
      of hypertension and proteinuria. Mothers with PE are known to develop endothelial
      dysfunction, but its effect on infants has been understudied, as newborns are
      often asymptomatic. Recent studies indicate that infants born from preeclamptic
      pregnancies develop endothelial dysfunction including higher blood pressure
      during childhood and an increased risk of stroke later in life. We hypothesize
      that PE reduces the number and function of fetal angiogenic progenitor cells and
      may contribute to this increased risk. We quantified 2 distinct types of
      angiogenic progenitors, pro-angiogenic circulating progenitor cells (CPCs) and
      endothelial colony-forming cells (ECFCs), from the umbilical cord blood of
      preeclamptic pregnancies and normotensive controls. Pro-angiogenic and
      nonangiogenic CPCs were enumerated via flow cytometry and ECFCs by cell culture.
      Additionally, we studied the growth, migration, and tube formation of ECFCs from
      PE and gestational age-matched normotensive control pregnancies. We found that PE
      resulted in decreased cord blood pro-angiogenic CPCs and ECFCs. Nonangiogenic
      CPCs were also decreased. Preeclamptic ECFCs demonstrated decreased growth and
      migration but formed tube-like structures in vitro similar to controls. Our
      results suggest that the preeclamptic environment alters the number and function
      of angiogenic progenitor cells and may increase the risk of later vascular
      disease.

PMID- 27879453
TI  - Effects of Supplementation of Human Endometriotic Fluids on In Vitro Mouse
      Preantral Follicle Culture.
AB  - This study aimed to investigate the potential detrimental effect of human
      endometriotic fluids (EFs) on in vitro growth of mouse preantral follicles.
      Preantral follicles (isolated from ovaries of 7- to 8-week-old mice) were
      cultured in growth medium for 10 days and then in maturation medium for 2 days.
      During in vitro culture, EF supernatants (0%, 2.5%, 5%, and 10%) were
      supplemented. Meiotic spindle integrity of metaphase II (MII) oocytes was
      analyzed. Hormone (17beta-estradiol and anti-Mullerian hormone [AMH]) levels in
      the final spent media were measured by enzyme-linked immunosorbent assay. The
      survival rates of follicles at day 10 were significantly lower in 3 EF
      supplemented groups (56.1%, 30.6%, and 6.2%; 83.6% in the nonsupplemented group).
      The production of total oocytes per initiated follicle was also significantly
      lower in the 3 EF-supplemented groups (34.7%, 18.4%, and 4.1%; 68.1% in the
      nonsupplemented group). Proportions of the oocyte with normal spindles were
      significantly lower in the 3 EF-supplemented groups (10%, 0% and 0%; 52% in the
      nonsupplemented group). In the final spent media, the level of 17beta-estradiol
      was significantly lower only in the 10% EF-supplemented group, and the level of
      AMH was significantly lower in all 3 EF-supplemented groups, when compared with
      the nonsupplemented group. During in vitro culture of mouse preantral follicles,
      the survival rate, oocyte acquisition, spindle integrity of MII oocytes, and AMH
      production were greatly affected by EF supplementation. These findings suggest a
      possibility of detrimental effects of endometriotic cysts on folliculogenesis in
      adjacent ovarian tissues.

PMID- 27879455
TI  - Diagnostic Care Pathways in Dementia.
AB  - OBJECTIVES: Increasing diagnostic rates of dementia is a national health
      priority; to meet this priority, improvement needs to be made to diagnostic
      services. It has been increasingly recognized that primary can play a significant
      role in the diagnostic journey for people with dementia, with some diagnostic
      services entirely located in primary care. This article reviews the extent of the
      involvement of primary care in diagnostic care pathways for people presenting
      with memory complaints within England, and presents examples of innovative
      approaches, which may be of interest to practitioners. METHOD: A rapid review was
      undertaken to identify articles outlining diagnostic care pathways for dementia
      involving primary care in England. RESULTS: Six articles relating to pathway
      evaluations and innovative approaches involving primary care were deemed suitable
      for inclusion in the review. CONCLUSIONS: The review found examples of diagnostic
      pathways and innovative practices being implemented in in primary care. These
      practices aligned to the strategic ambitions of the National Dementia Strategy.
      However, it was widely acknowledged that there is a need to improve
      postdiagnostic pathways; in particular, access to postdiagnostic support. This
      issue is being reflected in contemporary policy initiatives such as the
      Department of Health's 2016 Joint Declaration on postdiagnostic dementia care and
      support.

PMID- 27879454
TI  - Molecular Mechanisms of Androstenediol in the Regulation of the Proliferative
      Process of Human Endometrial Cells.
AB  - Proliferation in endometria of women with polycystic ovarian syndrome (PCOS) is
      increased, similar to the biosynthesis of androstenediol (estrogenic metabolite).
      As previously shown, in human endometrial cells, androstenediol increases CYCLIN
      D1 levels and KI67 and decreases P27 content. The objective of the present
      investigation was to determine the mechanisms by which androstenediol promotes
      endometrial cell-cycle progression. Estrogen receptor alpha (ERalpha) activation
      and changes in CYCLIN D1 and P27 levels were evaluated by Western blot in T-HESC
      and St-T1b endometrial cell lines, using receptor antagonists; activation of PI3K
      protein kinase B (AKT) and mitogen-activated protein kinases-extracellular signal
      regulated kinases (MAPK-ERK)1/2 pathways was evaluated using PI3K, MAPK/ERK
      kinase (MEK)1/2, and RNA-polymerase II inhibitors. The data showed that
      androstenediol treatment significantly increases CYCLIN D1 and decreases P27
      levels through ERalpha activation ( P < .05). In addition, an increase in
      AKT/ERK1/2 phosphorylations was determined ( P < .05). In the presence of RNA
      polymerase II inhibitor, phosphorylation of AKT/ERK1/2 decreased ( P < .05),
      meaning that endometrial cells need transcriptional activity to activate the
      kinases involved. It was also observed that PI3K action is required for P27 and
      CYCLIN D1 changes. Therefore, the action of androstenediol in endometria depends
      on PI3K-AKT and MAPK-ERK1/2 pathways activation, together with cell
      transcriptional machinery. This could be of clinical significance, as in
      pathologies such as PCOS, increased endometrial levels of androstenediol together
      with a high prevalence of endometrial hyperplasia and adenocarcinoma have been
      reported.

PMID- 27879456
TI  - Hindlimb spasticity after unilateral motor cortex lesion in rats is reduced by
      contralateral nerve root transfer.
AB  - Lower extremity spasticity is a common sequela among patients with acquired brain
      injury. The optimum treatment remains controversial. The aim of our study was to
      test the feasibility and effectiveness of contralateral nerve root transfer in
      reducing post stroke spasticity of the affected hindlimb muscles in rats. In our
      study, we for the first time created a novel animal hindlimb spastic hemiplegia
      model in rats with photothrombotic lesion of unilateral motor cortex and we
      established a novel surgical procedure in reducing motor cortex lesion-induced
      hindlimb spastic hemiplegia in rats. Thirty six rats were randomized into three
      groups. In group A, rats received sham operation. In group B, rats underwent
      unilateral hindlimb motor cortex lesion. In group C, rats underwent unilateral
      hindlimb cortex lesion followed by contralateral L4 ventral root transfer to L5
      ventral root of the affected side. Footprint analysis, Hoffmann reflex (H
      reflex), cholera toxin subunit B (CTB) retrograde tracing of gastrocnemius muscle
      (GM) motoneurons and immunofluorescent staining of vesicle glutamate transporter
      1 (VGLUT1) on CTB-labelled motoneurons were used to assess spasticity of the
      affected hindlimb. Sixteen weeks postoperatively, toe spread and stride length
      recovered significantly in group C compared with group B (P<0.001). Hmax (H-wave
      maximum amplitude)/Mmax (M-wave maximum amplitude) ratio of gastrocnemius and
      plantaris muscles (PMs) significantly reduced in group C (P<0.01). Average VGLUT1
      positive boutons per CTB-labelled motoneurons significantly reduced in group C
      (P<0.001). We demonstrated for the first time that contralateral L4 ventral root
      transfer to L5 ventral root of the affected side was effective in relieving
      unilateral motor cortex lesion-induced hindlimb spasticity in rats. Our data
      indicated that this could be an alternative treatment for unilateral lower
      extremity spasticity after brain injury. Therefore, contralateral neurotization
      may exert a potential therapeutic candidate to improve the function of lower
      extremity in patients with spastic hemiplegia.

PMID- 27879457
TI  - Protective Efficacy of Secondary Prophylaxis Against Visceral Leishmaniasis in
      Human Immunodeficiency Virus Coinfected Patients Over the Past 10 Years in
      Eastern India.
AB  - Coinfection with visceral leishmaniasis (VL) and human immunodeficiency virus
      (HIV) leads to frequent treatment failure, relapse, and death. In this
      retrospective analysis from eastern India (2005-2015), our primary objective was
      to ascertain the protective efficacy of secondary prophylaxis with monthly
      amphotericin B (AmB) given in patients with HIV-VL coinfection toward reducing
      relapse and mortality rates. The secondary objective was to compare clinical
      features, laboratory findings, and treatment outcomes in HIV-VL patients in
      contrast to VL monoinfection. Overall, 53 cases of HIV-VL and 460 cases of VL
      monoinfection were identified after excluding incomplete records. Initial cure
      rate was 96.23% in HIV-VL (27 received liposomal AmB and 26 AmB deoxycholate).
      All patients with initial cure (N = 51) were given antiretroviral therapy.
      Secondary prophylaxis (N = 27) was provided with monthly 1 mg/kg AmB (15
      liposomal, 12 deoxycholate). No relapse or death was noted within 6 months in the
      secondary prophylaxis group (relapse: none versus 18/24 [75%]; mortality: none
      versus 11/24 [45.8%]; P < 0.001 for both). Secondary prophylaxis remained the
      sole significant predictor against death in multivariate Cox regression model
      (hazard ratio = 0.09 [95% confidence interval = 0.03-0.31]; P < 0.001). HIV-VL
      patients had higher 6-month relapse rate, less relapse-free 12-month survival,
      and higher mortality (P < 0.001 each) than VL monoinfection. In conclusion, it
      appears from this study that secondary prophylaxis with monthly AmB might be
      effective in preventing relapse and mortality in HIV-VL.

PMID- 27879459
TI  - Clinical and Epidemiological Features of Paederus Dermatitis Among Nut Farm
      Workers in Turkey.
AB  - Paederus dermatitis is an acute irritant dermatitis resulting from contact with
      the hemolymph of Paederus beetles. This dermatitis mimics other infectious skin
      disorders, often resulting in diagnostic dilemmas. This study of 46 patients was
      conducted to increase awareness about Paederus dermatitis. Possible causes of a
      number of cases of Paederus dermatitis in Giresun, Turkey, were investigated
      using climate data and telephone interviews with the patients about risk factors.
      Insects caught by patients were identified at the species level. All patients
      were hazelnut farm workers and admitted to the hospital in the months during
      which the hazelnut harvesting occurs. Of the patients, 11 (23.91%) presented with
      painful and burning skin lesions, and 35 (70.09%) complained of itching. The neck
      was the most involved site (47.83%). The predominant type of lesion was
      erythematous plaque (84.78%). No pathological findings were detected by
      laboratory testing. Patients reported coming into contact with the insect during
      the daytime. Captured insects were identified as Paederus fuscipes. Although the
      weather and climate were optimal for P. fuscipes during June-October, patients
      were admitted to the hospital only during the hazelnut harvesting season (August
      September). The only risk factor identified among patients was occupation; hence
      we believe our study is the first to suggest that Paederus dermatitis is an
      occupational disease among hazelnut farm workers. We suggest that Paederus spp.
      may become a substantial threat due to global warming, especially among farm
      workers. Paederus dermatitis is not included in classic medical textbooks. It is
      necessary to increase awareness about this condition.

PMID- 27879458
TI  - The Changing Epidemiology of Human T-Cell Lymphotropic Virus Type 1 Infection in
      Peruvian Female Sex Workers, 1993-2010.
AB  - Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus to
      be reported and is associated with neoplastic, neurological, autoimmune, and
      infectious complications. HTLV-1 is endemic in Peru, with the highest prevalence
      reported among commercial sex workers. Seroprevalence data collected from
      Peruvian female sex workers (FSWs) working in Callao over three study periods
      between 1993 and 2010 were used to examine the secular trend in HTLV-1
      prevalence. Between 1993 and 2010, the prevalence of HTLV-1 decreased
      significantly from 14.5% to 3.1% (P < 0.01). The prevalence of HTLV-1
      seropositivity differed significantly by birth cohort (1922-1959, 1960-1969, 1970
      1979, and 1980-1992), and for each of the four birth cohorts, the prevalence did
      not significantly decrease by screening year (P > 0.07). There were no cases of
      HTLV-1 detected among FSW born after 1979 (N = 224). Participant characteristics
      associated with HTLV-1 seropositivity were birth in the Andes Mountains region,
      age, increased time in sex work, younger age of starting sex work, and human
      immunodeficiency virus (HIV) seropositivity. The secular trend in declining
      prevalence persisted after adjustment for age, time in sex work, place of birth,
      and HIV serostatus, with the odds of HTLV-1 infection decreasing approximately
      16% per year (adjusted odds ratio = 0.84, 95% confidence interval = 0.78, 0.90).
      The increasing use of condoms by later birth cohorts noted in our analysis, as
      well as the increasing availability of free condoms provided by the Peruvian
      government-which started in the late 1980s before this study-may have been
      responsible for declining HTLV seroprevalence.

PMID- 27879460
TI  - Effectiveness of Short-Course Meglumine Antimoniate (Glucantime(r)) for Treatment
      of Visceral Leishmaniasis: A 13-Year, Multistage, Non-Inferiority Study in Iran.
AB  - The World Health Organization's (WHO) recommendation is 28-day course of
      meglumine antimoniate (Glucantime(r), Sanofi Aventis, France) for the treatment
      of visceral leishmaniasis (VL). The aim of this study was to evaluate the
      effectiveness of a shorter duration of treatment in regions with low level of
      resistance to Glucantime. During 13 years, this study was conducted in three
      phases on 392 patients. In the pilot first phase, we performed splenic punctures
      in seven patients to assess the correlation between the changes in the parasite
      load during treatment with Glucantime and defervescence. With defervescence,
      parasite density was dramatically dropped (P = 0.014), propounding defervescence
      as a marker of parasitological response. On the basis of the results, we
      conducted a randomized trial on 75 patients, comparing the efficacy of
      continuation of Glucantime therapy for 1, 2, or 3 weeks after defervescence. The
      treatment course of 1 week after defervescence (mean = 11.7 days) was non
      inferior to that of 3 weeks (final cure rate, 96% versus 100%; P = 0.023). The
      third phase was a retrospective cohort study of 302 patients treated either with
      the WHO's regimen or for 7 days after defervescence (intervention group). Relapse
      was detected in 8.3% patients of the intervention group and in 5% patients
      following the WHO's regimen (P = 0.006 for non-inferiority). The final duration
      of treatment in intervention group was significantly shorter than standard course
      (13.3 +/- 2.6 versus 28 days; P < 0.001). In summary, treatment of VL with
      Glucantime for 1 week after defervescence was non-inferior to and appears to be
      an acceptable alternative to the standard 28-day course for patients in Iran who
      show a response to antimonial therapy.

PMID- 27879461
TI  - Unstable Malaria Transmission in the Southern Peruvian Amazon and Its Association
      with Gold Mining, Madre de Dios, 2001-2012.
AB  - The reemergence of malaria in the last decade in Madre de Dios, southern Peruvian
      Amazon basin, was accompanied by ecological, political, and socioeconomic changes
      related to the proliferation of illegal gold mining. We conducted a secondary
      analysis of passive malaria surveillance data reported by the health networks in
      Madre de Dios between 2001 and 2012. We calculated the number of cases of malaria
      by year, geographic location, intensity of illegal mining activities, and
      proximity of health facilities to the Peru-Brazil Interoceanic Highway. During
      2001-2012, 203,773 febrile cases were identified in Madre de Dios, of which
      30,811 (15.1%) were confirmed cases of malaria; all but 10 cases were due to
      Plasmodium vivax Cases of malaria rose rapidly between 2004 and 2007, reached
      4,469 cases in 2005, and then declined after 2010 to pre-2004 levels. Health
      facilities located in areas of intense illegal gold mining reported 30-fold more
      cases than those in non-mining areas (ratio = 31.54, 95% confidence interval [CI]
      = 19.28, 51.60). Finally, health facilities located > 1 km from the Interoceanic
      Highway reported significantly more cases than health facilities within this
      distance (ratio = 16.20, 95% CI = 8.25, 31.80). Transmission of malaria in Madre
      de Dios is unstable, geographically heterogeneous, and strongly associated with
      illegal gold mining. These findings highlight the importance of spatially
      oriented interventions to control malaria in Madre de Dios, as well as the need
      for research on malaria transmission in illegal gold mining camps.

PMID- 27879462
TI  - Detection of the Leprosy Agent Mycobacterium lepromatosis in South America and
      Europe.

PMID- 27879465
TI  - Why Is Diagnosing Pediatric Malnutrition Important?
AB  - The literature indicates that pediatric malnutrition is more common than the
      number of times it is actually diagnosed. A new pediatric malnutrition definition
      is now available with criteria to make the diagnosis. If pediatric malnutrition
      is present, it should be diagnosed for financial, educational, and research
      purposes as well as the effects on patient development and mortality. These
      reasons extend beyond the health of an individual patient to potential impacts on
      society as a whole. When all of these reasons are examined and added, making the
      diagnosis of pediatric malnutrition becomes an obligation of the pediatric
      caregiver.

PMID- 27879466
TI  - Doctors protest against bill to dissolve the Medical Council of India.

PMID- 27879463
TI  - A Tale of Two Flaviviruses: A Seroepidemiological Study of Dengue Virus and West
      Nile Virus Transmission in the Ouest and Sud-Est Departments of Haiti.
AB  - Though plans to eliminate malaria from the island of Hispaniola have recently
      received much attention, arbovirus surveillance continues to be largely neglected
      in Haiti. To support surveillance efforts and encourage vector-control
      strategies, a cross-sectional study of dengue virus (DENV) and West Nile virus
      (WNV) transmission was conducted using standard seroepidemiological methods.
      Blood samples (N = 673) were collected from 278 males and 395 females from three
      locations in the Ouest and Sud-Est Departments of Haiti. Serum was separated and
      tested for the presence of anti-DENV and anti-WNV immunoglobulin G (IgG)
      antibodies using an indirect enzyme-linked immunosorbent assay (ELISA). Anti-DENV
      IgG antibodies were detected in 72.1% (95% confidence interval [CI] = 68.7, 75.5)
      of the sample population; with no significant differences in seroprevalence by
      study location, participant gender, or age group (P > 0.1, in all tests). Anti
      WNV IgG antibodies were detected in only 1% (95% CI = 0.3, 1.8) of the sample
      population, all which originated from participants located in Gressier. The high
      prevalence of anti-DENV IgG antibodies among all age groups, including those in
      the youngest age group (2-5 years of age), suggests hyperendemic transmission of
      DENV in the Ouest and Sud-Est Departments of Haiti. In contrast, the relative
      absence of anti-WNV IgG antibodies, even among older population members, further
      supports the notion that WNV transmission in this population is largely absent.
      These findings highlight the large burden of disease from DENV and the need for
      enhanced arbovirus surveillance and implementation of vector control strategies
      throughout Haiti.

PMID- 27879464
TI  - Severe Pleuropulmonary Paragonimiasis Caused by Paragonimus mexicanus Treated as
      Tuberculosis in Ecuador.
AB  - A 30-year-old male, from a subtropical region of Ecuador, was hospitalized with a
      5-year history of persistent cough with rusty brown sputum, chest pain, and
      progressive dyspnea. The patient underwent thoracic surgery 3 years ago for
      pleural effusion and subsequently received a 9-month regimen treatment of
      tuberculosis. However, there was no clinical resolution and symptoms became
      progressively worse. A chest radiograph and computerized tomography scan showed
      several small nodules in both lungs. Eggs of Paragonimus spp. were observed in
      sputum smears, but the smears were negative for acid-fast bacilli. Molecular
      characterization of eggs by the internal transcribed spacer-2 regions identified
      them as Paragonimus mexicanus The patient was treated with praziquantel and
      tested negative parasitologically for 12 months. There was clinical resolution of
      the cough and expectoration, but dyspnea and chest pain persisted.

PMID- 27879468
TI  - Relationship Between Plasma Levels of Soluble CD40 Ligand and the Presence and
      Severity of Isolated Coronary Artery Ectasia.
AB  - OBJECTIVE: We aimed to investigate whether soluble CD40 ligand (CD40L) levels are
      higher in patients with isolated coronary artery ectasia (CAE) compared to
      patients with angiographically normal coronary arteries and those with stable
      coronary artery disease (CAD). MATERIALS AND METHODS: In all, 55 patients with
      isolated CAE without stenosis, 55 with stable CAD, and 55 control participants
      with angiographically normal coronary arteries were included. The CAE severity
      was determined according to the Markis classification. Plasma levels of soluble
      CD40 ligand were measured by enzyme-linked immunosorbent assay. RESULTS: The
      baseline characteristics of the 3 groups were similar. Plasma levels of soluble
      CD40 ligand were significantly higher in patients with CAE and CAD than in
      controls (2.6 +/- 3.1 ng/mL and 2.0 +/- 3.1 ng/mL vs 1.8 +/- 2.1 ng/mL, P =
      .004). No difference was found between the CAE and CAD groups. Soluble CD40
      ligand level was significantly higher in the type 1 Markis subgroup than that in
      the type 3 or type 4 subgroups ( P = .01). A receiver operating characteristic
      curve analysis revealed that soluble CD40 ligand level >1.2 ng/mL identified
      patients with isolated CAE. CONCLUSION: Significantly higher levels of soluble
      CD40 ligand were detected in patients with CAE than that in control participants
      with normal coronary arteries, suggesting that soluble CD40 ligand may be
      involved in the pathogenesis of CAE. The CD40-CD40 ligand system likely plays a
      role in the pathogenesis of CAE.

PMID- 27879467
TI  - Meiotic spindle assembly and chromosome segregation in oocytes.
AB  - Oocytes accumulate maternal stores (proteins, mRNAs, metabolites, etc.) during
      their growth in the ovary to support development after fertilization. To preserve
      this cytoplasmic maternal inheritance, they accomplish the difficult task of
      partitioning their cytoplasm unequally while dividing their chromosomes equally.
      Added to this complexity, most oocytes, for reasons still speculative, lack the
      major microtubule organizing centers that most cells use to assemble and position
      their spindles, namely canonical centrosomes. In this review, we will address
      recent work on the mechanisms of meiotic spindle assembly and chromosome
      alignment/segregation in female gametes to try to understand the origin of errors
      of oocyte meiotic divisions. The challenge of oocyte divisions appears indeed not
      trivial because in both mice and humans oocyte meiotic divisions are prone to
      chromosome segregation errors, a leading cause of frequent miscarriages and
      congenital defects.

PMID- 27879469
TI  - Frequency of Common VKORC1 Polymorphisms and Their Impact on Warfarin Dose
      Requirement in Pakistani Population.
AB  - Polymorphisms in vitamin K epoxide reductase complex subunit 1 (VKORC1) gene lead
      to interindividual variability in warfarin dose requirement. The characterization
      of genotype frequency distribution is required in different populations for
      construction of customized dosing algorithms to enhance the efficacy and reduce
      the toxicity of warfarin therapy. This study was carried out in Pakistani
      population to evaluate the contribution of common VKORC1 polymorphisms to
      warfarin therapy. A total of 550 stable patients taking warfarin were enrolled
      after medical history, physical examination, and laboratory investigations.
      Single blood sample was collected after informed consent. Genomic DNA was
      extracted and genotype analysis for VKORC1 1173C>T and VKORC1-1639G>A
      polymorphisms was done by polymerase chain reaction-restriction fragment length
      polymorphism assay. A number of samples were also analyzed by direct DNA
      sequencing for validation of results. Data were analyzed using SPSS version 20.
      Genotype frequency distributions of VKORC1 1173C>T and VKORC1-1639G>A were found
      to be different from other populations. Both of these polymorphisms did not
      demonstrate significant effect on warfarin dose requirement. Although Cytochrome
      P450 2C9 (CYP2C9) and VKORC1 polymorphisms together attributed only 3.8%
      variability in warfarin dose but it was statistically significant ( p value =
      .004). It is concluded that there is a need to study genotype frequency
      distribution and their effect on warfarin dose variability among different
      populations due to diversity in outcome. At the same time, no effect on warfarin
      dose variation explained by VKORC1 polymorphisms and small variability explained
      by studied genotypes stresses the need for exploration of more genetic and
      nongenetic factors in Pakistani population.

PMID- 27879470
TI  - Incidence and Management of Thrombotic and Thromboembolic Complications Following
      the Norwood Procedure: A Systematic Review.
AB  - BACKGROUND: The stage 1 Norwood procedure and its variants represent the first
      step of palliation for hypoplastic left heart syndrome. Although appropriate
      postoperative thromboprophylaxis is integral, significant variance remains across
      institutional practices. The purpose of this systematic review is to estimate the
      incidence of thrombosis and thromboembolism following the Norwood or modified
      Blalock-Taussig shunt procedure and examine current thromboprophylaxis regimens.
      METHODS: Ovid MEDLINE and Embase were searched from January 2000 to June 2016 for
      primary studies explicitly reporting incidence of thrombosis, thromboembolism
      (strokes and pulmonary embolisms), or shunt occlusion in neonates, infants, and
      children undergoing the Norwood procedure or any variant. All-cause mortality was
      a secondary outcome of interest. RESULTS: Of 887 identified articles, 15 cohort
      studies were deemed eligible, the majority including modified Blalock-Taussig
      shunt patients. Reported incidence of thrombosis ranged from 0% to 40%;
      thromboembolic events were rarely reported. Overall mortality ranged from 4.5% to
      31.3% across studies. Although most studies involved the long-term
      acetylsalicylic acid use, thromboprophylaxis strategies varied across studies.
      Due to substantial variability in event rates, no correlation was identified with
      thrombotic complications. DISCUSSION: Clinical practice guidelines recommend that
      patients receive intraoperative unfractionated heparin therapy and either aspirin
      or no antithrombotic therapy postoperatively. Our findings suggest a substantial
      risk of thrombosis and thromboembolism and demonstrate substantial variation in
      thromboprophylaxis practices. CONCLUSION: Although postoperative
      thromboprophylaxis seems optimal, it remains controversial whether the long-term
      aspirin use is most effective. Our findings highlight the lack of a gold-standard
      thromboprophylaxis strategy and emphasize the need for more consistency.

PMID- 27879471
TI  - Molecular Basis of Congenital Factor XIII Deficiency in Iran.
AB  - Factor XIII deficiency (FXIIID) is an extremely rare autosomal recessive disorder
      that has the highest incidence in Iran. The FXIIID is primarily due to mutations
      in the FXIII-A gene, most of which are unique. In the current study, we report
      all identified mutations among Iranian patients. Among 483 patients, 366 (75.8%)
      were molecularly analyzed; 11 different mutations were observed. Of 11, 8 (72.7%)
      are missense, whereas the remaining 3 (27.3%) are deletion/insertion. Among these
      patients, 347 (94.9%) had the unique mutation of c.562T>C and 5 (1.4%) had the
      c.233G>A mutation. c.1226G>A, c.2111G>A, and c.1142T>A are also common, whereas
      other mutations, including 3 missense and 3 deletion/insertion, were observed
      only in single patient. Although, in most cases, FXIII mutations are unique and
      restricted to a specific family, this differs in Iran where a considerable number
      of identified mutations, recurrently observed, appear to be due to the high rate
      of consanguinity.

PMID- 27879472
TI  - Can patient-reported measurements of pain be used to improve cancer pain
      management? A systematic review and meta-analysis.
AB  - PURPOSE: Cancer pain is a distressing and complex experience. It is feasible that
      the systematic collection and feedback of patient-reported outcome measurements
      (PROMs) relating to pain could enhance cancer pain management. We aimed to
      conduct a systematic review of interventions in which patient-reported pain data
      were collected and fed back to patients and/or professionals in order to improve
      cancer pain control. METHODS: MEDLINE, EMBASE and CINAHL databases were searched
      for randomised and non-randomised controlled trials in which patient-reported
      data were collected and fed back with the intention of improving pain management
      by adult patients or professionals. We conducted a narrative synthesis. We also
      conducted a meta-analysis of studies reporting pain intensity. RESULTS: 29
      reports from 22 trials of 20 interventions were included. PROM measures were used
      to alert physicians to poorly controlled pain, to target pain education and to
      link treatment to management algorithms. Few interventions were underpinned by
      explicit behavioural theories. Interventions were inconsistently applied or
      infrequently led to changes in treatment. Narrative synthesis suggested that
      feedback of PROM data tended to increase discussions between patients and
      professionals about pain and/or symptoms overall. Meta-analysis of 12 studies
      showed a reduction in average pain intensity in intervention group participants
      compared with controls (mean difference=-0.59 (95% CI -0.87 to -0.30)).
      CONCLUSIONS: Interventions that assess and feedback cancer pain data to patients
      and/or professionals have so far led to modest reductions in cancer pain
      intensity. Suggestions are given to inform and enhance future PROM feedback
      interventions.

PMID- 27879474
TI  - Oscillatory expression in Escherichia coli mediated by microRNAs with
      transcriptional and translational time delays.
AB  - The primary objective of this study is to study oscillatory expression of gene
      regulatory network in Escherichia coli mediated by microRNAs (sRNAs) with
      transcriptional and translational time delays. Motivated by the regulation of
      gene expression proposed by Shimoni et al. (Molecular Systems Biology, 2007), a
      general model of delayed gene regulatory network by sRNAs is formulated. This
      model can well describe many practical architectures of gene regulatory network
      by sRNAs, particularly when both transcriptional and translational time delays
      are introduced. Two functional issues on oscillatory expression of the gene
      regulatory network, i.e. stability and bifurcation, are investigated.
      Furthermore, an explicit algorithm determining the direction of Hopf bifurcation
      and stability of bifurcating periodic solutions is presented. It turns out that
      both transcriptional and translational time delays can induce gene expression in
      E. coli to be oscillatory even when its deterministic counterpart exhibits no
      oscillations. Moreover, the obtained results are in consistence with the
      experimental observations found in the biological literatures (Elowitz MB et al.:
      Nature, 2000, 403, pp. 335-338; Lennart Hilbert et al.: Mol. BioSyst, 2011, 7,
      pp. 2599-2607), which demonstrates that both transcriptional and translational
      time delays play an important role in the gene regulatory process of E. coli.

PMID- 27879473
TI  - An unusual cause of tinnitus: essential palatal myoclonus.

PMID- 27879476
TI  - Interactive cooperation and hierarchical operation of microRNA and transcription
      factor crosstalk in human transcriptional regulatory network.
AB  - Transcriptional regulation of gene expression is an essential cellular process
      that is arranged by transcription factors (TFs), microRNAs (miRNA) and their
      target genes through a variety of mechanisms. Here, we set out to reconstruct a
      comprehensive transcriptional regulatory network of Homo sapiens consisting of
      experimentally verified regulatory information on miRNAs, TFs and their target
      genes. We have performed topological analyses to elucidate the transcriptional
      regulatory roles of miRNAs and TFs. When we thoroughly investigated the network
      motifs, different gene regulatory scenarios were observed; whereas, mutual TF
      miRNA regulation (interactive cooperation) and hierarchical operation where
      miRNAs were the upstream regulators of TFs came into prominence. Otherwise,
      biological process specific subnetworks were also constructed and integration of
      gene and miRNA expression data on ovarian cancer was achieved as a case study to
      observe dynamic patterns of the gene expression. Meanwhile, both co-operation and
      hierarchical operation types were determined in active ovarian cancer and process
      specific subnetworks. In addition, the analysis showed that multiple signals from
      miRNAs were integrated by TFs. Our results demonstrate new insights on the
      architecture of the human transcriptional regulatory network, and here we present
      some lessons we gained from deciphering the reciprocal interplay between miRNAs,
      TFs and their target genes.

PMID- 27879475
TI  - Inferring catalysis in biological systems.
AB  - In systems biology, one is often interested in the communication patterns between
      several species, such as genes, enzymes or proteins. These patterns become more
      recognisable when temporal experiments are performed. This temporal communication
      can be structured by reaction networks such as gene regulatory networks or
      signalling pathways. Mathematical modelling of data arising from such networks
      can reveal important details, thus helping to understand the studied system. In
      many cases, however, corresponding models still deviate from the observed data.
      This may be due to unknown but present catalytic reactions. From a modelling
      perspective, the question of whether a certain reaction is catalysed leads to a
      large increase of model candidates. For large networks the calibration of all
      possible models becomes computationally infeasible. We propose a method which
      determines a substantially reduced set of appropriate model candidates and
      identifies the catalyst of each reaction at the same time. This is incorporated
      in a multiple-step procedure which first extends the network by additional latent
      variables and subsequently identifies catalyst candidates using similarity
      analysis methods. Results from synthetic data examples suggest a good performance
      even for non-informative data with few observations. Applied on CD95 apoptotic
      pathway our method provides new insights into apoptosis regulation.

PMID- 27879477
TI  - Robust group fused lasso for multisample copy number variation detection under
      uncertainty.
AB  - One of the most important needs in the post-genome era is providing the
      researchers with reliable and efficient computational tools to extract and
      analyse this huge amount of biological data, in which DNA copy number variation
      (CNV) is a vitally important one. Array-based comparative genomic hybridisation
      (aCGH) is a common approach in order to detect CNVs. Most of methods for this
      purpose were proposed for one-dimensional profiles. However, slightly this focus
      has moved from one- to multi-dimensional signals. In addition, since
      contamination of these profiles with noise is always an issue, it is highly
      important to have a robust method for analysing multi-sample aCGH profiles. In
      this study, the authors propose robust group fused lasso which utilises the
      robust group total variations. Instead of l2,1 norm, the l1 - l2 M-estimator is
      used which is more robust in dealing with non-Gaussian noise and high corruption.
      More importantly, Correntropy (Welsch M-estimator) is also applied for fitting
      error. Extensive experiments indicate that the proposed method outperforms the
      state-of-the art algorithms and techniques under a wide range of scenarios with
      diverse noises.

PMID- 27879478
TI  - Occurrence of HIV eradication for preexposure prophylaxis treatment with a
      deterministic HIV model.
AB  - The authors examine the human immunodeficiency virus (HIV) eradication in this
      study using a mathematical model and analyse the occurrence of virus eradication
      during the early stage of infection. To this end they use a deterministic HIV
      infection model, modify it to describe the pharmacological dynamics of
      antiretroviral HIV drugs, and consider the clinical experimental results of
      preexposure prophylaxis HIV treatment. They also use numerical simulation to
      model the experimental scenario, thereby supporting the clinical results with a
      model-based explanation. The study results indicate that the protocol employed in
      the experiment can eradicate HIV in infected patients at the early stage of the
      infection.

PMID- 27879479
TI  - Identify signature regulatory network for glioblastoma prognosis by integrative
      mRNA and miRNA co-expression analysis.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive type of primary
      brain tumor in adults. Patients with this disease have a poor prognosis. The
      objective of this study is to identify survival-related individual genes (or
      miRNAs) and miRNA -mRNA pairs in GBM using a multi-step approach. First, the
      weighted gene co-expression network analysis and survival analysis are applied to
      identify survival-related modules from mRNA and miRNA expression profiles,
      respectively. Subsequently, the role of individual genes (or miRNAs) within these
      modules in GBM prognosis are highlighted using survival analysis. Finally, the
      integration analysis of miRNA and mRNA expression as well as miRNA target
      prediction is used to identify survival-related miRNA -mRNA regulatory network.
      In this study, five genes and two miRNA modules that significantly correlated to
      patient's survival. In addition, many individual genes (or miRNAs) assigned to
      these modules were found to be closely linked with survival. For instance,
      increased expression of neuropilin-1 gene (a member of module turquoise)
      indicated poor prognosis for patients and a group of miRNA -mRNA regulatory
      networks that comprised 38 survival-related miRNA -mRNA pairs. These findings
      provide a new insight into the underlying molecular regulatory mechanisms of GBM.

PMID- 27879480
TI  - Adaptive modelling of gene regulatory network using Bayesian information
      criterion-guided sparse regression approach.
AB  - Inferring gene regulatory networks (GRNs) from microarray expression data are an
      important but challenging issue in systems biology. In this study, the authors
      propose a Bayesian information criterion (BIC)-guided sparse regression approach
      for GRN reconstruction. This approach can adaptively model GRNs by optimising the
      l1-norm regularisation of sparse regression based on a modified version of BIC.
      The use of the regularisation strategy ensures the inferred GRNs to be as sparse
      as natural, while the modified BIC allows incorporating prior knowledge on
      expression regulation and thus avoids the overestimation of expression regulators
      as usual. Especially, the proposed method provides a clear interpretation of
      combinatorial regulations of gene expression by optimally extracting regulation
      coordination for a given target gene. Experimental results on both simulation
      data and real-world microarray data demonstrate the competent performance of
      discovering regulatory relationships in GRN reconstruction.

PMID- 27879481
TI  - Role of non-motile microtubule-associated proteins in virus trafficking.
AB  - Viruses are entirely dependent on their ability to infect a host cell in order to
      replicate. To reach their site of replication as rapidly and efficiently as
      possible following cell entry, many have evolved elaborate mechanisms to hijack
      the cellular transport machinery to propel themselves across the cytoplasm. Long
      range movements have been shown to involve motor proteins along microtubules
      (MTs) and direct interactions between viral proteins and dynein and/or kinesin
      motors have been well described. Although less well-characterized, it is also
      becoming increasingly clear that non-motile microtubule-associated proteins
      (MAPs), including structural MAPs of the MAP1 and MAP2 families, and microtubule
      plus-end tracking proteins (+TIPs), can also promote viral trafficking in
      infected cells, by mediating interaction of viruses with filaments and/or motor
      proteins, and modulating filament stability. Here we review our current knowledge
      on non-motile MAPs, their role in the regulation of cytoskeletal dynamics and in
      viral trafficking during the early steps of infection.

PMID- 27879482
TI  - Unusual structures of CCTG repeats and their participation in repeat expansion.
AB  - CCTG repeat expansion in intron 1 of the cellular nucleic acid-binding protein
      (CNBP) gene has been identified to be the genetic cause of myotonic dystrophy
      type 2 (DM2). Yet the underlying reasons for the genetic instability in CCTG
      repeats remain elusive. In recent years, CCTG repeats have been found to form
      various types of unusual secondary structures including mini-dumbbell (MDB),
      hairpin and dumbbell, revealing that there is a high structural diversity in CCTG
      repeats intrinsically. Upon strand slippage, the formation of unusual structures
      in the nascent strand during DNA replication has been proposed to be the culprit
      of CCTG repeat expansions. On the one hand, the thermodynamic stability, size,
      and conformational dynamics of these unusual structures affect the propensity of
      strand slippage. On the other hand, these structural properties determine whether
      the unusual structure can successfully escape from DNA repair. In this short
      overview, we first summarize the recent advances in elucidating the solution
      structures of CCTG repeats. We then discuss the potential pathways by which these
      unusual structures bring about variable sizes of repeat expansion, high strand
      slippage propensity and efficient repair escape.

PMID- 27879483
TI  - Comparison of ex vivo stability of copeptin and vasopressin.
AB  - BACKGROUND: Copeptin, part of the vasopressin precursor, is increasingly used as
      marker for vasopressin and is claimed to have better ex vivo stability. However,
      no study has directly compared the ex vivo stability of copeptin and vasopressin.
      METHODS: Blood of ten healthy volunteers was collected in EDTA tubes. Next, we
      studied the effect of various pre-analytical conditions on measured vasopressin
      and copeptin levels: centrifugation speed, short-term storage temperature and
      differences between whole blood and plasma, long-term storage temperature and
      repeated freezing and thawing. The acceptable change limit (ACL), indicating the
      maximal percentage change that can be explained by assay variability, was used as
      cut-off to determine changes in vasopressin and copeptin. RESULTS: The ACL was
      25% for vasopressin and 19% for copeptin. Higher centrifugation speed resulted in
      lower vasopressin levels, whereas copeptin concentration was unaffected. In whole
      blood, vasopressin was stable up to 2 h at 25 degrees C and 6 h at 4 degrees C.
      In plasma, vasopressin was stable up to 6 h at 25 degrees C and 24 h at 4 degrees
      C. In contrast, copeptin was stable in whole blood and plasma for at least 24h at
      both temperatures. At -20 degrees C, vasopressin was stable up to 1 month and
      copeptin for at least 4 months. Both vasopressin and copeptin were stable after 4
      months when stored at -80 degrees C and -150 degrees C. Vasopressin concentration
      decreased after four freeze-thaw cycles, whereas copeptin concentration was
      unaffected. CONCLUSION: Vasopressin levels were considerably affected by pre
      analytical conditions, while copeptin levels were stable. Therefore, a strict
      sample handling protocol for measurement of vasopressin is recommended.

PMID- 27879484
TI  - Herpes simplex type 2 encephalitis and methotrexate medication: a fortuitous or
      causative association in a patient with spondyloarthritis?
AB  - It is unclear whether immunosuppression is a risk factor for herpes encephalitis.
      Herein, we describe a rare case of herpes simplex virus type 2 encephalitis in a
      patient treated with low-dose methotrexate for HLA-B27-associated
      spondyloarthritis. The patient was successfully treated with acyclovir but
      presented sequelae of encephalitis. Here we discuss the possible role of low-dose
      methotrexate therapy as a risk factor of neurological herpes reactivation and
      severe disease. The host-related and viral risk factors are also addressed.

PMID- 27879485
TI  - Patients' views on fecal microbiota transplantation: an acceptable therapeutic
      option in inflammatory bowel disease?
AB  - BACKGROUND: Fecal microbiota transplantation (FMT) represents a new therapeutic
      option that has been studied in two randomized-controlled trials in ulcerative
      colitis patients. Our study aimed to identify patients' views on the use of this
      novel therapeutic approach. METHODS: Using an anonymous questionnaire, we
      obtained data from 574 inflammatory bowel disease (IBD) patients on their
      knowledge and willingness to undergo FMT. RESULTS: A large proportion of IBD
      patients (53.5%) are unaware that FMT is a therapeutic option in Clostridium
      difficile infection and potentially IBD. More responders preferred FMT (31.5%) to
      a study with a new medication (28.9%), although the difference was not
      significant (P=0.37), and the preferred way of transplantation was colonoscopy
      (49.7%). In all, 38.3% preferred a family member as a donor, but there was fear
      about the procedure (41.5% mentioned fear of infectious diseases, 26.5% expressed
      disgust). The knowledge of successful FMT treatment in other patients was
      important for 82.2% of responders and for 50.7%, a discussion with a specialist
      would likely change their opinion about FMT. CONCLUSION: FMT represents a
      therapeutic procedure that is of interest for IBD patients. As FMT has been
      receiving increasing interest as an alternative treatment in IBD and more studies
      on FMT in IBD are being carried out, it is important to learn about the
      knowledge, attitude, and preferences of patients to provide better education to
      patients on this topic. However, there are reservations because of the fact that
      data on the benefits of FMT in IBD are controversial and several limitations
      exist on the use of FMT in IBD.

PMID- 27879486
TI  - Prospective interventional study of tenofovir in pregnancy to prevent vertical
      transmission of hepatitis B in highly viremic women.
AB  - BACKGROUND: The risk of vertical transmission of hepatitis B virus (HBV)
      increases as maternal HBV DNA increase, despite serovaccination to newborns.
      METHODS: From 1 July 2012 to 1 January 2016, all pregnant women in Lariboisiere
      Hospital, Paris, France, with HBV DNA of 5 log10 IU/ml and above were
      administered tenofovir from week 28 of pregnancy until delivery. HBV DNA was
      measured at months 1, 2 of tenofovir and at delivery. The newborns were
      serovaccinated, tested for hepatitis B surface antigen, hepatitis B core antibody
      (HBcAb)+/-HBV DNA, and hepatitis B surface antibody (HBsAb) when aged 9 months,
      and then 24 months. This study was registered in http://www.ClinicalTrials.gov
      (NCT02039362). RESULTS: Thirty-one women gave birth to 37 newborns. Maternal HBV
      DNA at baseline was 8.23 log10 IU/ml and above in 12 pregnancies. The mean
      (median) HBV DNA were 4.4+/-1.2 (4.8), 3.3+/-1.7 (3.8), and 2.1+/-1.9 (2.0) log10
      IU/ml at months 1, 2 of tenofovir and at delivery, respectively. Twenty-seven
      newborns were followed up: none of the 19 children aged 9 months or older was
      positive for hepatitis B surface antigen when aged 9 months; 14 children tested
      positive for HBcAb (probably transferred maternal antibodies, not found when aged
      24 months) and for HBsAb without HBV DNA. Four of the 19 children showed HBsAb
      without HBcAb, the last being doubtful for HBcAb and HBsAb without HBV DNA. Eight
      newborns aged less than 9 months were not tested. CONCLUSION: Tenofovir from week
      28 of pregnancy to highly viremic HBV women plus serovaccination to newborns
      could prevent chronic and past infection.

PMID- 27879487
TI  - Electrocochleography in Cochlear Implant Recipients With Residual Hearing:
      Comparison With Audiometric Thresholds.
AB  - OBJECTIVES: To determine whether electrocochleography (ECoG) thresholds,
      especially cochlear microphonic and auditory nerve neurophonic thresholds,
      measured using an intracochlear electrode, can be used to predict pure-tone
      audiometric thresholds following cochlear implantation in ears with residual
      hearing. DESIGN: Pure-tone audiometric thresholds and ECoG waveforms were
      measured at test frequencies from 125 to 4000 Hz in 21 Advanced Bionics cochlear
      implant recipients with residual hearing in the implanted ear. The "difference"
      and "summation" responses were computed from the ECoG waveforms measured from two
      alternating phases of stimulation. The interpretation is that difference
      responses are largely from the cochlear microphonic while summating responses are
      largely from the auditory nerve neurophonic. The pure-tone audiometric thresholds
      were also measured with same equipment used for ECoG measurements. RESULTS:
      Difference responses were observed in all 21 implanted ears, whereas summation
      response waveforms were observed in only 18 ears. The ECoG thresholds strongly
      correlated (r = 0.87, n = 150 for difference response; r = 0.82, n = 72 for
      summation response) with audiometric thresholds. The mean difference between the
      difference response and audiometric thresholds was -3.2 (+/-9.0) dB, while the
      mean difference between summation response and audiometric thresholds was -14 (+/
      11) dB. In four out of 37 measurements, difference responses were measured to
      frequencies where no behavioral thresholds were present. CONCLUSIONS: ECoG
      thresholds may provide a useful metric for the assessment of residual hearing in
      cochlear implant subjects for whom it is not possible to perform behavioral
      audiometric testing.

PMID- 27879488
TI  - 18F-NaF PET Demonstrating Unusual Focal Tracer Activity in the Brain.
AB  - A 60-year-old man with enlarged prostate, hypertension, and diabetes was referred
      for F-NaF PET/CT to evaluate possible metastatic lesions. The patient appeared
      asymptomatic on the day of the study, without any signs indicating stroke.
      Patient also had no known history of malignancy or cerebrovascular disease. He
      had mild elevation of the prostate-specific antigen level, and biopsy of his
      prostate was not performed. Patient had long-standing history of chronic back
      pain and abdominal pain. The PET bone scan demonstrated a large area of very
      intense tracer uptake in the brain. A subsequent brain MRI revealed prior stroke
      in the same area.

PMID- 27879490
TI  - Intense Uptake in Amyloidosis of the Seminal Vesicles on 68Ga-PSMA PET Mimicking
      Locally Advanced Prostate Cancer.
AB  - We report a case of benign senile seminal vesicle amyloidosis demonstrating
      intense Ga-prostate-specific membrane antigen (PSMA) uptake on PET/CT. A 68-year
      old man underwent staging PSMA PET/CT and MRI for biopsy-proven prostate
      adenocarcinoma. There was an intense focus of Ga-PSMA uptake in the primary
      malignancy, as well as symmetrical intense uptake in the seminal vesicles
      bilaterally that was reported as multifocal disease with local invasion. Final
      histology after radical prostatectomy showed amyloidosis of the seminal vesicles
      without any evidence of prostate cancer. Care should be taken in the
      interpretation of seminal vesicle PSMA uptake to avoid overstaging.

PMID- 27879489
TI  - Breast Fibroadenoma With Increased Activity on 68Ga DOTATATE PET/CT.
AB  - Fibroadenoma is the most common benign breast tumor in women of reproductive age,
      carrying little to no risk of breast cancer development. We report on a case of a
      woman with history of neuroendocrine tumor who on follow-up imaging tests
      underwent whole-body PET/CT study using Ga DOTATATE. The scan showed increased
      focal activity in the right breast, which was biopsied revealing a fibroadenoma.
      The presented data suggests cell surface overexpression of somatostatin receptors
      by this benign breast tumor. Moreover, this finding emphasizes the need for
      cautious interpretation of Ga DOTATATE-avid breast lesions that could mimic
      malignancy in neuroendocrine tumor patients.

PMID- 27879491
TI  - 18F-FDG PET/CT in Renal Infections: Evidence of Acute Pyelonephritis in a
      Horseshoe Kidney.
AB  - A 58-year-old paraplegic patient was prescribed F-FDG for persistent inflammatory
      syndrome after aortic surgery for dissection. The examination was performed on a
      Siemens mCT Flow PET/CT and shows a moderate prostate uptake, related to
      prostatitis on self-catheterization and a focal renal cortical hypermetabolism of
      the left medial midpole of a horseshoe kidney, which corresponds to renal
      parenchyma on the CT, and suggests pyelonephritis, confirmed by Tc-DMSA SPECT/CT.

PMID- 27879493
TI  - Socioeconomic status and site-specific cancer incidence, a Bayesian approach in a
      French Cancer Registries Network study.
AB  - The aim of this study was to identify and compare cancer sites whose incidence is
      influenced by social deprivation. The study population comprised 189 144 cases of
      cancer diagnosed between 2006 and 2009, recorded in member registries of the
      French Network of Cancer Registries. Social environment was assessed at an
      aggregate level using the European Deprivation Index. The association between
      incidence and socioeconomic status was assessed by a geographical Bayesian
      Poisson model enabling a reduction of the overall variability and smoothing of
      the relative risks by sharing information provided by multiple geographic units.
      For cancers of the stomach, liver, lips-mouth-pharynx, and lung, a higher
      incidence in deprived populations was found for both sexes as well as for cancers
      of the larynx, esophagus, pancreas, and bladder in men and cervical cancer in
      women. For melanoma, prostate, testis, ovarian, and breast cancer, a higher
      incidence was observed in affluent populations. The highest relative risks of the
      lowest social class compared with the highest social class were found for larynx
      [relative risk (RR)=1.67 (1.43-1.95)], lips-mouth-pharynx [RR=1.89 (1.72-2.07)],
      and lung cancer [RR=1.59 (1.50-1.68)] in men and for cervix [RR=1.62 (1.40-1.88)]
      and lips-mouth-pharynx [RR=1.56 (1.30-1.86)] cancer in women. By estimating the
      burden of social deprivation on cancer incidence throughout France, this study
      enables us to measure the gains that could be achieved by implementing targeted
      prevention efforts.

PMID- 27879492
TI  - Altered Nulling of Myocardium and Blood Pool.

PMID- 27879495
TI  - Fish consumption and prostate cancer risk and mortality in a Danish cohort study.
AB  - Within the Danish 'Diet, Cancer and Health' cohort, we aimed to investigate the
      association between prediagnostic fish intake (total, lean, fatty) and (a)
      incidence of total and high-grade prostate cancer and (b) the risk of all-cause
      and prostate cancer-specific mortality among men with prostate cancer. Among 27
      178 men, 1690 prostate cancer cases were identified through 2012. Of these, 1042
      had a Gleason score of 7 or above and 498 had a Gleason score of 8 or above at
      the time of diagnosis; 364 died (n=228 from prostate cancer) during follow-up
      through 2013. Cox proportional hazard models were used for the statistical
      analyses. No association between any type of fish intake and risk of total
      prostate cancer or high-grade prostate cancer (Gleason score>=7 or >=8) was
      found. For all-cause mortality, we found no association for any type of fish
      intake. For prostate cancer-specific mortality, only a higher intake of fatty
      fish was associated with a higher mortality [per daily 25 g increment in intake
      (mortality rate ratio=1.27; 95% confidence interval: 1.04-1.55; P=0.02)]. In
      conclusion, no strong association was found between fish consumption and the risk
      of or mortality from prostate cancer. Only a higher intake of fatty fish was
      associated with a higher risk of prostate cancer-specific mortality.

PMID- 27879494
TI  - Gynecologists and human papillomavirus DNA testing: exploring knowledge,
      attitudes, and practice in Italy.
AB  - The aim of this survey was to examine the knowledge, attitudes, and behavior of
      gynecologists in terms of human papillomavirus (HPV) DNA testing as a primary
      screening tool for cervical cancer. A national cross-sectional web survey was
      carried out through multistage sampling using an overall sample of 1000
      gynecologists. Gynecologists were asked to fill in a self-administered
      questionnaire exploring their knowledge, attitudes, and practice toward cervical
      cancer screening and HPV-DNA testing. A total of 582 gynecologists completed the
      web questionnaire. Of these, 24.5% were uncertain on the higher sensitivity of
      HPV-DNA compared with the Pap test, whereas 19% were uncertain on the role of the
      HPV-DNA test as a primary test in women younger than 30 years old and only 44.9%
      knew that a negative HPV-DNA test allows for an extension of the test interval to
      5 years. Most gynecologists showed a definite positive attitude on the role of
      screening for cervical cancer prevention and were prepared to accept new
      technologies. The HPV-DNA test was considered highly effective by 86.9%, whereas
      94% recommend/perform HPV-DNA tests in women older than 30 years of age; 25.5%
      performed HPV-DNA as a primary test, followed by a Pap test in those cases that
      were positive. Only 56.3% recommended/performed HPV-DNA tests 1 year after a
      positive HPV-DNA test, followed by a negative Pap test, whereas 42.9% recommended
      colposcopy. Although the use of the HPV-DNA test is very widespread among Italian
      gynecologists performing cervical cancer screening, there is lack of
      standardization of practices according to current guidelines.

PMID- 27879496
TI  - Death Due to Pulmonary Alveolar Proteinosis.
AB  - Presented are 2 cases of death from pulmonary alveolar proteinosis (PAP). Within
      the past 2 years, there have been 2 cases of rare nonneoplastic lung disease that
      consists of the filling of the alveoli of the lung by a periodic acid-Schiff
      stain-positive lipoproteinaceous material. This condition bears a certain
      resemblance to interstitial lung disease and/or Pneumocystitis jirovecci
      infection of the lungs. The presented cases were clinically diagnosed as
      interstitial lung disease. In the first case presented, the decedent was admitted
      to hospital with diagnosis of pneumonia but died in hospital despite observation
      and treatment. Autopsy examination revealed that instead of an infection, there
      was amorphous granular eosinophilic proteinaceous fluid in irregular clumps, with
      scattered foamy macrophages and cholesterol clefts and cracks in the lung
      alveoli. The second case was suspected of electrocution. There were no findings
      pointing to or against the possibility of electrocution, whereas the alveoli and
      terminal bronchioles were filled with amorphous granular eosinophilic
      lipoproteinaceous substance. The alveolar structure was well preserved, and the
      interstitium had no or mild chronic inflammatory cells. In both cases, the
      lipoproteinaceous material stained deep pink with periodic acid-Schiff stain. The
      gross and microscopic examination in the second case also signified pulmonary
      alveolar proteinosis.The following report describes 2 cases of this uncommon
      disorder, with cause of death confirmed by postmortem examination.

PMID- 27879497
TI  - The Differential Diagnosis Between Natural Death and Homicide, an Everlasting
      Challenge for the Forensic Pathologist: An Exemplar Case Report.
AB  - Most of the work performed by the forensic expert is to find proof for different
      plausible hypotheses that may be used in a trial to serve justice purposes when
      the "identity" of a case is already unveiled. Yet the previous phase of the
      investigation is also of great importance, and sometimes (like in the presented
      case), it represents the core element of the entire investigation. The
      appropriate determination of the differential diagnosis between a natural death
      and a death of forensic interest (ie, homicide) is the first and crucial step in
      the classification of a case. This article analyzes the case of the body of a man
      found lying on the border of a country road with his wrists tied up with rope and
      the resulting investigation performed by the medicolegal forensic expert. In the
      end, as more specific examinations where performed aimed to find the truth, the
      final conclusions excluded a violent death and confirmed that the cause of the
      death was an acute myocardial infarction.

PMID- 27879498
TI  - Enhancement of death receptor 4-mediated apoptosis and cytotoxicity in renal cell
      carcinoma cells by anisomycin.
AB  - Renal cell carcinoma (RCC) is one of the most drug-resistant malignancies, and an
      effective therapy is lacking for metastatic RCC. Anisomycin is known to inhibit
      protein synthesis and induce ribotoxic stress. The aim of this study was to
      explore whether anisomycin enhances the cytotoxic effects of mapatumumab, a human
      agonistic monoclonal antibody specific for death receptor 4 (DR4), in human RCC
      cells. We examined the cytotoxicity of anisomycin alone and in combination with
      mapatumumab in human RCC cell lines and primary RCC cell cultures. RCC cells
      treated with anisomycin showed cytotoxicity in a dose-dependent manner. Anisomyin
      in combination with mapatumumab showed a synergistic effect not only in two human
      RCC cell lines but also in five primary RCC cell cultures. The synergy between
      anisomycin and mapatumumab for cytotoxicity was also observed for apoptosis.
      Interestingly, anisomycin significantly increased DR4 expression at both the mRNA
      and the protein level. Furthermore, the combination-induced cytotoxicity was
      significantly suppressed by a human recombinant DR4:Fc chimeric protein. The
      combination of anisomycin and mapatumumab also enhanced the activity of caspases
      8 and 3, the downstream molecules of death receptors. These findings indicate
      that anisomycin sensitizes RCC cells to DR4-mediated apoptosis through the
      induction of DR4, suggesting that combinational treatment with anisomycin and
      mapatumumab might represent a novel therapeutic strategy for the treatment of
      RCC.

PMID- 27879500
TI  - Implications of Preterm Birth for Maternal Mental Health and Infant Development.
AB  - Preterm birth remains a major contributor to infant mortality and morbidity
      including neurodevelopmental delay and childhood disability. Mothers experiencing
      a preterm birth are at risk for maternal mental health issues, inclusive of
      depression and posttraumatic stress disorder (PTSD), which may affect mother
      infant attachment and infant development. Depression and PTSD, frequently
      comorbid, following preterm birth and relationships between these symptoms,
      maternal-infant attachment, and infant development are reviewed. Assessments and
      interventions potentially capable of benefitting mother and infant are noted. The
      need for healthcare professionals to intervene prenatally and at postpartum is
      significant as maternal distress remains one of the most consistent factors
      related to infant development. Although depression has received much attention in
      the literature as a risk factor for preterm birth, impaired attachment, and
      delayed infant development, some of the consequences of PTSD have only recently
      gained research attention. A few studies support the role of PTSD in impaired
      maternal-infant attachment; yet, it is unclear whether preterm infants of mothers
      experiencing symptoms of PTSD following birth are at a higher risk for motor
      development problems. Because early mother-infant interactions are influenced by
      prematurity as well as maternal mental health, consideration for home
      interventions that stimulate infant development and encourage mother-infant
      relationships concurrently are important. Directed interventions may be
      beneficial for infant development and aid in strengthening the mother-infant
      relationship, potentially reducing depression and PTSD symptoms in the mother.

PMID- 27879499
TI  - Impact of Spherical Aberration Terms on Multifocal Contact Lens Performance.
AB  - PURPOSE: To investigate the impact of the primary (PSA) and secondary (SSA)
      spherical aberration terms on visual performance (VP) in presbyopes, as measured
      using multifocal (MFCL) soft contact lenses on eye. METHODS: Seventeen presbyopes
      (age: 55.1 +/- 6.9 years) wore seven commercial lenses (four center-near (MFCL
      N), one center-distance (MFCL D), one bifocal, and one single vision control).
      Unaided and with each lens on eye, the PSA and SSA terms were obtained with an
      aberrometer, the BHVI-EyeMapper (low illumination, natural and 4 mm pupil
      diameter). High- and low-contrast distance visual acuity, contrast sensitivity,
      high-contrast visual acuities at near, and range of clear vision were measured.
      In addition, subjective VP variables included clarity of vision at distance and
      near, ghosting, and overall vision satisfaction. Pearson's correlation was used
      to determine the association between the PSA and SSA terms and the VP variables.
      RESULTS: PSA (natural pupil) was more negative (P < .05) with the MFCL N (mean
      PSA = -0.053 +/- 0.080 MUm) and bifocal (PSA = +0.005 +/- 0.067 MUm) lenses and
      more positive with the MFCL D lens (PSA = +0.208 +/- 0.160 MUm) than the control
      (+0.067 +/- 0.072 MUm). SSA (natural pupil) was significantly more positive for
      the MFCL N lenses (mean SSA = +0.025 +/- 0.029 MUm) compared to the control (SSA
      = -0.001 +/- 0.017 MUm). PSA and SSA terms were significantly (P < .05)
      correlated with 78% and 56% of VP variables, respectively, but the correlation
      coefficients were weak, ranging between |0.210| and |0.334|. Although distance
      variables showed improved VP with more positive PSA or negative SSA, most near
      variables showed improved VP with more negative PSA. Range of clear focus was
      greater for more negative PSA terms. CONCLUSIONS: The amount and direction of PSA
      and SSA terms, as measured with different MFCLs on eye, can affect VP at
      different distances. Results of this study may provide useful information when
      designing new or optimize existing MFCLs for improved VP at specific distances.

PMID- 27879501
TI  - Introducing Allergenic Food into Infants' Diets: Systematic Review.
AB  - PURPOSE: The purpose of this systematic review was to explore the association
      between timing of introduction of potentially allergenic foods to infants and
      development of food allergies. METHODS: CINAHL, Medline, PubMed, Science Direct,
      and Web of Science were searched using the terms solid food, complementary food,
      or infant feeding combined with allergy or hypersensitivity for articles
      published in English in 2000 or later. Inclusion criteria were 1) primary
      research articles with 2) a focus on association between introduction of
      complementary foods including potentially allergenic foods into diets of infants
      less than 12 months of age and development of food allergies. Articles were
      excluded if they were 1) not primary research, 2) about complementary foods only
      (without specificity of allergenic foods), or 3) on allergic conditions other
      than food allergy (such as asthma or eczema). RESULTS: The initial literature
      search yielded 533 articles; 14 articles met inclusion criteria. Level of
      evidence of each study was determined with the SORT criteria. Results found that
      delayed introduction of solid foods in general and allergenic foods in particular
      was not associated with decreased risk for allergic diseases among high and low
      risk infants. Later introduction was associated with increased risk for allergy
      development. CLINICAL IMPLICATIONS: For infants at low risk for development of
      food allergies, providers should advise caregivers to introduce potentially
      allergenic foods with other solid foods between 4 and 6 months of age when
      children show an interest in eating solids. Infants at high risk for peanut
      allergy, should be evaluated by an allergy specialist prior to introduction of
      peanuts and work with providers to create an individualized plan for introduction
      of peanuts and other allergenic foods as needed.

PMID- 27879503
TI  - Should Central Cord Syndrome With Continued Spinal Cord Compression Without a
      Fracture Undergo Urgent (<24 h) Surgical Decompression?

PMID- 27879502
TI  - Labor Nurses' Views of Their Influence on Cesarean Birth.
AB  - BACKGROUND: As part of an ongoing study about nurse staffing during labor and
      birth sponsored by the Association of Women's Health, Obstetric, and Neonatal
      Nurses (AWHONN), outcomes that may be linked to aspects of labor nursing were
      considered. The purpose of this study was to see if labor nurses felt they
      influenced whether a woman has a cesarean birth. These data were used to
      determine if cesarean birth should be included as an outcome measure in the
      multistate labor nurse staffing study. METHODS: Focus groups were used to explore
      the role of labor nurses and cesarean birth. Participants were attending the
      AWHONN national convention in 2015. Two open-ended questions were asked: 1) Do
      labor nurses influence whether a woman has a cesarean? 2) What specific things do
      you do as a labor nurse to help a woman avoid a cesarean? RESULTS: Two focus
      groups were held (n = 15 and n = 9). Nurses overwhelmingly agreed nursing care
      can influence mode of birth. They described multiple strategies routinely used to
      help a woman avoid a cesarean, which were categorized into three main themes:
      support, advocacy, and interactions with physicians. Support was emotional,
      informational, and physical. Advocacy involved advocating for women and helping
      women advocate for themselves. Nurses tried to focus on positive aspects of labor
      progress when communicating with physicians. Descriptions of interactions with
      some physicians implied less than optimal teamwork and lack of collaboration.
      CONCLUSION: Labor nurses are likely influential in whether some women have a
      cesarean. They reported consistently taking an active role to help women avoid a
      cesarean. Promoting vaginal birth as appropriate to the clinical situation was a
      high priority. Trust, partnership, and respect for roles and responsibilities of
      each discipline were not evident in some of the clinical situations nurses
      described.

PMID- 27879504
TI  - Database Research in Spine Surgery.
AB  - With the introduction of several publicly available national databases to study
      surgical outcomes, the use of such databases for spine surgery research has
      increased dramatically. These databases allow researchers to retrospectively
      examine data from a large sample of patients. This rise in the use of national
      databases to study surgical outcomes parallels an increasing reliance by
      administrators, payers, and third-party graders to evaluate surgical quality with
      the use of large administrative databases. A good understanding of the most
      commonly utilized databases for spine surgery is important for critical
      assessment of this growing body of literature.

PMID- 27879505
TI  - The Effect of Transpedicular Screw Design on Its Performance in Vertebral Bone
      Under Tensile Loads: A Parametric Study.
AB  - STUDY DESIGN: A biomechanical study using bovine thoracolumbar spines. OBJECTIVE:
      To study investigated whether thread design parameters aimed at altering the
      state of stress at the screw-bone interface increase the screw's holding power.
      SUMMARY AND BACKGROUND DATA: Internal spinal fixators utilizing transpedicular
      screw fixation are used to achieve early stabilization of the injured spine in a
      range of clinical conditions. Despite advances in the design of internal spinal
      fixation systems, implant loosening, and catastrophic failures at the screw-bone
      interface remains a serious complication in adult spine surgery. Although the
      performance of the screws in the vertebral bone critically depends on ability of
      screw thread design to provide and maintain adequate bone purchase, the effect of
      individual thread design parameters on screw performance and the failure process
      of the screw-bone interface, remains unclear. METHODS: On the basis of the AO
      Schanz thread, this parametric study used 96 lumbar bovine vertebrae instrumented
      with 19 screw designs to investigate the effects of pitch, ratio of major to
      minor diameter, screw insertion depth, and major diameter, on screw performance
      under pure tensile loading. The effect of vertebral morphometry on screw
      performance and the extent of damage within the failed screw-bone interface were
      evaluated. RESULTS: The increase in screw insertion depth, screw pitch, and the
      ratio of major to minor diameter, significantly affected screw performance under
      tensile loads. Complex interactions existed between the major diameter and each
      of the design variables. Vertebral morphometry had little effect on screw
      performance while the damage within the failed bone-screw interface confined to
      the immediate region of the screw threads. CONCLUSIONS: Design variables, able to
      reduce shear stresses or modify the complex stress profile at the bone-screw
      interface, are more effective in preventing early failure of the interface.

PMID- 27879506
TI  - Fatty Degeneration of the Paraspinal Muscle in Patients With Degenerative Lumbar
      Kyphosis: A New Evaluation Method of Quantitative Digital Analysis Using MRI and
      CT Scan.
AB  - STUDY DESIGN: A comparative case-control study. OBJECTIVE: The aim of this study
      was to quantify the degree of paraspinal muscle changes in degenerative lumbar
      kyphosis (DLK) patients using magnetic resonance imaging and computed tomography
      scanning. SUMMARY OF BACKGROUND DATA: Although the pathophysiology of DLK is not
      completely understood, extensive degeneration and weakness of the lumbar extensor
      muscles are thought to underlie the condition in most patients. However, there is
      no ideal method to quantify the degree of fat infiltration and atrophy of the
      paraspinal muscles in patients with DLK. MATERIALS AND METHODS: The study group
      comprised 20 patients with DLK and 20 healthy volunteers. The cross-sectional
      areas of the psoas, erector spinae (ES), multifidus (MF), quadratus lumborum, and
      vertebral body were measured. The ratio between the cross-sectional area of the
      muscle and the vertebral body was used to evaluate lumbar muscularity. The degree
      of fatty change was evaluated by measuring the ratio between the mean signal
      intensity of the muscle and that of the subcutaneous fat within regions of
      interest. RESULTS: Muscularity in the MF and ES was not significantly different
      between the DLK and control groups at L1, L2, or L3, but was significantly
      different at L4 (ES, P=0.001; MF, P=0.001) and L5 (ES, P=0.001; MF, P=0.015). The
      mean signal intensities of the ES and MF were higher in the DLK group than in the
      control group at all levels. The degree of fatty change in the ES and MF was
      significantly higher in the DLK group than in the control group (P<0.05).
      CONCLUSIONS: Quantitative analysis using magnetic resonance imaging and computed
      tomography scanning showed differences in paraspinal muscle volume and fatty
      degeneration between patients with DLK and healthy volunteers. This evaluation
      method may be useful for measuring the extent of paraspinal muscle degeneration.

PMID- 27879507
TI  - Pedicle Screw Combined With Lateral Mass Screw Fixation in the Treatment of
      Basilar Invagination and Congenital C2-C3 Fusion.
AB  - STUDY DESIGN: Clinical evaluation of a surgical fixation technique featuring
      combined use of pedicle screw and lateral mass screw (LMS). OBJECTIVE:
      Introduction of a novel technique for the treatment of congenital C2-C3 fusion
      and basilar invagination (BI). SUMMARY OF BACKGROUND: Posterior occipitocervical
      fixation using C2 pedicle screw was widely used for BI. However, in cases where
      BI is concurrent with congenital C2-C3 fusion, the C2 pedicles tend to be thinner
      than that in normal population and hence more likely to fail. We prompted to
      tackle the issue by combining the pedicle screw with the additional use of LMS in
      attempt to strengthen the fixation. METHODS: Twenty-five patients who underwent
      combined pedicle screw with LMS fixation were retrospectively studied. The
      instrument position, fusion status, and complications were analyzed. RESULTS:
      None had spinal cord or vertebral artery injury. The average follow-up time was
      20 months. Solid fusion was achieved in 23 patients (92%) as detected
      radiologically. Two cases suffered from recurred BI and instrument failure but
      eventually achieved solid fusion between the occiput and C2 was after revision.
      Among all 25 patients, 4 suffered from complications including instruments
      failure, cerebrospinal fluid leakage, and intracranial infection. CONCLUSIONS:
      The clinical outcome indicates that the technique is reliable for the treatment
      of BI with congenital C2-C3 fusion.

PMID- 27879509
TI  - Surgical Site Infections Following the Transoral Approach: A Review of 172
      Consecutive Cases.
AB  - STUDY DESIGN: A retrospective review. OBJECTIVE: The aim of this study was to
      discuss the characteristics, treatment, and incidence of surgical site infection
      (SSI) following transoral approach surgery. SUMMARY OF BACKGROUND DATA: One of
      the primary risks associated with transoral approach surgery is postoperative
      SSI. Few reports exist detailing the specific circumstances, treatment options,
      and incidence of SSIs following transoral approach surgery in a large series of
      consecutive cases. MATERIALS AND METHODS: From January 2005 to September 2010,
      172 consecutive transoral surgeries were performed at a single tertiary referral
      center. Information on patients, treatment methods, and complication incidence
      and resolution was collected. RESULTS: There were 6 cases of SSI (3.5%), all in
      complex craniocervical patients. Of the 6 cases, 2 (1.2%) were isolated local
      infections, whereas 4 (2.3%) resulted in intracranial infection. Of those with
      intracranial infections, 3 (75%) were instrumented, whereas 1 (25%) was
      uninstrumented. Four intraoperative dural lacerations occurred in the entire
      series (2.3%), all of which developed into intracranial infections. Full SSI
      resolution occurred in 4 (67%) patients following active treatment: in 3 of 4
      patients (75%) with intracranial infections and in 1 of 2 patients (50%) with
      local infections. Of the 2 remaining unresolved cases, one patient (intracranial)
      refused removal of instrumentation and subsequently discontinued the treatment,
      and the other (local) experienced a delayed postoperative infection and died
      after not receiving treatment because of economic reasons. Following full
      implementation of care guidelines to avoid SSI in transoral patients, no further
      SSIs were observed. CONCLUSIONS: SSI rate following transoral exposure has
      increased from the authors' earlier reports (0%), likely because of the
      increasing complexity and instrumentation of transoral approach cases.
      Cerebrospinal fluid leakage caused by dural injury highly predisposes to
      intracranial infection. Lumbar puncture, cranial computed tomography, continuous
      drainage diversion, and intrathecal injection of antibiotics are adequate methods
      of treatment. Strict consideration of surgical indications, adequate preoperative
      preparation, careful surgical technique to avoid dural injury, and postoperative
      oropharyngeal care are important steps for preventing SSI through the transoral
      approach.

PMID- 27879508
TI  - Effect of an Annular Closure Device (Barricaid) on Same-Level Recurrent Disk
      Herniation and Disk Height Loss After Primary Lumbar Discectomy: Two-year Results
      of a Multicenter Prospective Cohort Study.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: To evaluate whether an
      annular closure device could be implanted safely to reduce same-level recurrent
      disk herniation, or attenuate disk height loss and improve the outcome after
      lumbar discectomy. SUMMARY OF BACKGROUND DATA: Same-level recurrent disk
      herniation, disk height loss, and progressive degeneration are common
      complications and sequelae after lumbar discectomy. Techniques to reduce these
      consequences may improve outcomes. METHODS: Forty-six consecutive patients
      undergoing lumbar discectomy for single-level herniated disk at 2 institutions
      were followed prospectively with clinical and radiographic evaluations at 6 weeks
      and 3, 6, 12, and 24 months (control cohort). A second consecutive cohort of 30
      patients undergoing 31 lumbar discectomies with implantation of an annular
      closure device was followed similarly. Incidence of recurrent disk herniation,
      disk height loss, the leg and back pain visual analog scale (VAS), and the
      Oswestry Disability Index were assessed at each follow-up. RESULTS: Cohorts were
      well matched at baseline. By 2 years of follow-up, symptomatic recurrent same
      level disk herniation occurred in 3 (6.5%) patients in the control cohort versus
      0 (0%) patients in the annular repair cohort (P=0.27). A trend of greater
      preservation of disk height was observed in the annular repair versus the control
      cohort 3 months (7.9 vs. 7.27 mm, P=0.08), 6 months (7.81 vs. 7.18 mm, P=0.09),
      and 12 months (7.63 vs. 6.9 mm, P=0.06) postoperatively. The annular closure
      cohort reported less leg pain (VAS-LP: 5 vs. 16, P<0.01), back pain (VAS-BP: 13
      vs. 22, P<0.05), and disability (Oswestry Disability Index: 16 vs. 22, P<0.05) 1
      year postoperatively. CONCLUSIONS: Implantation of a novel annular repair device
      was associated with greater maintenance of disk height and improved 1-year leg
      pain, back pain, and low-back disability. Recurrent disk herniation did not occur
      in any patient after annular repair. Closure of annular defect after lumbar
      discectomy may help preserve the physiological disk function and prevent long
      term disk height loss and associated back and leg pain.

PMID- 27879510
TI  - Clinical and Radiographic Outcomes of C1 Laminectomy Without Fusion in Patients
      With Cervical Myelopathy That Is Associated With a Retro-odontoid Pseudotumor.
AB  - PURPOSE: A retro-odontoid pseudotumor that is not associated with rheumatoid
      arthritis or hemodialysis is clinically rare. The majority of surgeons select
      transoral resection as the surgical treatment, often followed by posterior fusion
      or posterior decompression and fusion. In contrast, some authors have reported
      success with simple decompression without posterior stabilization in cases where
      atlanto-axial instability (AAI) is either absent or minor. In this study, we have
      evaluated the clinical and radiographic outcomes of C1 laminectomy without fusion
      as the surgical treatment for patients with cervical myelopathy that is
      associated with a retro-odontoid pseudotumor. METHODS: A retrospective chart
      review was conducted on 10 patients who underwent C1 laminectomy without fusion
      for cervical myelopathy associated with a retro-odontoid pseudotumor. RESULTS:
      The average follow-up time was 29 months. All cases were graded as Ranawat grade
      3a or 3b. After surgery, myelopathy improved in all of the patients. In 2
      patients, the atlas-dens interval increased in the flexed position; however, this
      did not result in any clinical problems. The size of the retro-odontoid mass
      (measured on magnetic resonance images at least 12 mo after surgery) decreased in
      4 of the 10 cases. CONCLUSIONS: AAI progression and mass enlargement were our
      primary concerns for this surgical option; however, C1 laminectomy did not cause
      severe AAI progression, no patients showed serious mass enlargement, and all
      patients demonstrated neurological improvement. This surgical strategy is
      beneficial especially for elderly patients given the risks of other surgical
      options that use an anterior transoral approach or posterior fusion.

PMID- 27879511
TI  - C2-C3 Anterior Cervical Fusion: Technical Report.
AB  - STUDY DESIGN: Retrospective review of patients at a university hospital.
      OBJECTIVE: To describe the anterior approach for cervical discectomy and fusion
      (ACDF) at C2-C3 level and evaluate its suitability for treatment of instability
      and degenerative disease in this region. SUMMARY OF BACKGROUND DATA: The anterior
      approach is commonly used for ACDF in the lower cervical spine but is used less
      often in the high cervical spine. METHODS: We retrospectively reviewed a database
      of consecutive cervical spine surgeries performed at our institution to identify
      patients who underwent ACDF at the C2-C3 level during a 10-year period.
      Demographic data, clinical indications, surgical technique, complications, and
      immediate results were evaluated. RESULTS: Of the 11 patients (7 female, 4 male;
      mean age 46 y) identified, 7 were treated for traumatic fractures and 4 for
      degenerative disk disease. Three patients treated for myelopathy showed
      improvement in mean Nurick grade from 3.6 to 1.3. Pain was significantly improved
      in all patients who had preoperative pain. Solid bony fusion was achieved in 5 of
      7 patients at 3-month follow-up. Complications included dysphagia in 4 patients
      (which resolved in 3), aspiration pneumonia, mild persistent dysphonia, and
      construct failure at C2 requiring posterior fusion. One patient died of a
      pulmonary embolism 2 weeks postoperatively. CONCLUSIONS: ACDF at the C2-C3 level
      is an option for the treatment of high cervical disease or trauma but is
      associated with a higher rate of approach-related morbidity. Familiarity with
      local anatomy may help to reduce complications. ACDF at C2-C3 appears to have a
      fusion rate similar to ACDF performed at other levels.

PMID- 27879512
TI  - UHMWPE Sublaminar Wires in Posterior Spinal Instrumentation: Stability and
      Biocompatibility Assessment in an Ovine Pilot Study.
AB  - STUDY DESIGN: An animal study. OBJECTIVE: To explore ultra-high molecular weight
      polyethylene (UHMWPE) sublaminar wires in spinal surgery and to assess stability
      and biocompatibility of the UHMWPE instrumentation in an ovine model. SUMMARY OF
      BACKGROUND DATA: Sublaminar wiring is a well-established technique in segmental
      scoliosis surgery. However, during introduction and/or removal of the metal
      sublaminar wires, neurological problems can occur. Abrasion after cutting metal
      wires for removal can lead to damage to the dural sac. Sublaminar wires have to
      withhold large forces and breakage of the wires can occur. Different types of
      sublaminar wires have been developed to address these problems. UHMWPE sublaminar
      wires can potentially substitute currently used metal sublaminar metal wires. In
      vivo testing and biocompatibility analysis of UHMWPE wires are recommended before
      clinical use in spinal surgery. MATERIALS AND METHODS: In 6 immature sheep,
      pedicle screws were instrumented at lumbar level L4 and attached with titanium
      rods to 4 thoracolumbar vertebrae using 3- and 5-mm-wide UHMWPE sublaminar wiring
      constructions in 5 animals. Titanium sublaminar wires were applied in 1 animal to
      function as a control subject. After a follow-up period of 16 weeks, the animals
      were sacrificed and the spines were isolated. Radiographs and computed tomography
      (CT) scans were made to assess stability of the instrumentation. The vertebrae
      were dissected for macroscopic and histologic evaluation. RESULTS: None of the
      wires had loosened and the instrumentation remained stable. CT scans and
      radiographs showed no signs of failure of the instrumentation and no neurological
      complications occurred. Although several bony bridges were seen on CT, growth was
      observed at the operated levels. Biocompatibility was assessed by macroscopical
      and histologic analysis, showing no signs of dural or epidural inflammation.
      CONCLUSIONS: This pilot animal study shows that UHMWPE sublaminar wiring is a
      safe technique. The UHMWPE wires are biocompatible and provide sufficient
      stability in spinal instrumentation. Heterotopic ossification because of periost
      reactions in the ovine spine led to some restrictions in this study.

PMID- 27879513
TI  - High-grade Neuroendocrine Carcinoma of the Lung With Carcinoid Morphology: A
      Study of 12 Cases.
AB  - Twelve lung neuroendocrine tumors with morphologic features of carcinoid tumors
      but with mitotic count >10/2 mm are reported. There were 7 males and 5 females,
      with age ranging from 56 to 78 years. Four cases were from never-smokers. All
      tumors showed architectural and cytomorphologic features of carcinoid tumor,
      including organoid nesting, insular, trabecular, or acinar growth, and tumor
      cells with low nucleocytoplasmic ratio, abundant cytoplasm, ovoid to round
      nuclei, and salt and pepper chromatin. Angulated or confluent nesting, insular or
      lobular growth pattern was also seen. Nuclear irregularities and anisonucleosis
      were focally present. Mitotic count ranged from 11 to 61/2 mm. Punctate-type
      necrosis was present in 8 tumors. Anaplastic cytology, large infarct-type
      necrosis, desmoplasia, or marked inflammatory infiltrate was not found in any of
      the tumors. One tumor occurred in the background of diffuse idiopathic pulmonary
      neuroendocrine hyperplasia. All tumors were treated by resection, and all but 1
      patient subsequently developed metastasis, and 7 died of the tumor. For
      metastatic tumors, 4 patients were treated by platinum-based chemotherapy with no
      apparent response, whereas 3 other patients were treated by combined capecitabine
      and temozolomide-novel chemotherapy for well-differentiated neuroendocrine
      tumor/carcinoid tumor-2 of them responded. This subset of tumor would be
      classified as large cell neuroendocrine carcinoma according to the current WHO
      classification scheme, but their clinical and pathologic features appear to have
      more in common with the carcinoid tumor group than large cell neuroendocrine
      carcinoma, therefore, identification of this subset may be relevant for further
      therapeutic management.

PMID- 27879514
TI  - Primary Cutaneous T-Cell Lymphomas Showing Gamma-Delta (gammadelta) Phenotype and
      Predominantly Epidermotropic Pattern are Clinicopathologically Distinct From
      Classic Primary Cutaneous gammadelta T-Cell Lymphomas.
AB  - Primary cutaneous gamma-delta (gammadelta) T-cell lymphoma is a rare disease that
      typically involves the dermis and subcutis. Cases of primary cutaneous T-cell
      lymphomas showing gammadelta phenotype and predominantly epidermotropic pattern
      (EgammadeltaTCL) are not well defined. In this series, cases of primary cutaneous
      T-cell lymphomas showing gammadelta phenotype were reviewed and classified as
      predominantly epidermotropic (EgammadeltaTCL) when >75% of lymphoma cells resided
      in the epidermis or predominantly dermal and/or subcutaneous (DSgammadeltaTCL).
      Clinical, pathologic, and immunophenotypic features were compared in 27 biopsies
      from 13 patients of EgammadeltaTCL and 13 biopsies from 7 patients of
      DSgammadeltaTCL. The lymphoma cells were diffusely positive for CD3 and T-cell
      receptor (TCR)gamma, mostly positive for granzyme B and TIA-1, variably positive
      for CD8, CD7, and CD30, and negative for CD4 and TCRbeta. Two patients with
      EgammadeltaTCL had dissemination to lymph nodes and 1 to the lung; 1 patient with
      DSgammadeltaTCL had gastrointestinal involvement. The median survival of patients
      with EgammadeltaTCL was not reached, and with a median follow-up of 19.2 months,
      3/13 died. In contrast, the median survival of patients with DSgammadeltaTCL was
      10 months, and after a median follow-up of 15.6 months, 5/5 died (P<0.01).
      EgammadeltaTCL is a rare presentation of cutaneous T-cell lymphoma that can be
      distinguished from DSgammadeltaTCL based on the extent of epidermotropism and has
      a better prognosis and longer median survival than DSgammadeltaTCL. However,
      although EgammadeltaTCL resembles mycosis fungoides clinically and
      histologically, a subset of EgammadeltaTCL is more likely to behave more
      aggressively than typical mycosis fungoides.

PMID- 27879515
TI  - Atypical Spindle Cell Lipomatous Tumor: Clinicopathologic Characterization of 232
      Cases Demonstrating a Morphologic Spectrum.
AB  - The classification of atypical adipocytic neoplasms with spindle cell features
      remains challenging. To better define this category of low-grade lipomatous
      neoplasms, we present herein the clinical, histologic, and immunohistochemical
      characteristics of a large series of 232 atypical spindle cell lipomatous tumors.
      The lesions affected 140 males and 92 females, at an average age of 54 years
      (range, 6 to 87 y), clinically presenting as a persistent or enlarging mass with
      a median size of 5 cm. The anatomic distribution of the tumors was wide,
      predominating in the limbs and limb girdles (147 cases, 63%), mainly in the hands
      and feet (17% and 11%, respectively), with equal distribution between
      subcutaneous and deeper locations. Microscopic examination revealed a spectrum of
      histologic appearances. All cases consisted of a poorly marginated proliferation
      of mildly atypical spindle cells set in a fibrous or myxoid stroma, with a
      variably prominent admixed adipocytic component showing variation in adipocyte
      size and scattered nuclear atypia, frequently with univacuolated or
      multivacuolated lipoblasts. Tumor cellularity and the relative proportion of the
      different components were very variable. Tumor margins were often ill defined
      with invasion into surrounding tissues. Two tumors showed morphologic features
      reminiscent of dedifferentiation. By immunohistochemistry, the neoplastic spindle
      cells expressed CD34 (64%), S100 protein (40%) and, less frequently, desmin
      (23%). Expression of Rb was lost in 57% of cases examined. MDM2 and CDK4 were
      never coexpressed and FISH for MDM2 amplification was consistently negative,
      highlighting critical biological differences from atypical lipomatous
      tumor/dedifferentiated liposarcoma. The morphologic differential diagnosis of
      atypical spindle cell lipomatous tumor is broad, and includes spindle cell
      lipoma, diffuse neurofibroma, mammary-type myofibroblastoma, dermatofibrosarcoma
      protuberans, fat-forming solitary fibrous tumor, and morphologically low-grade
      malignant peripheral nerve sheath tumor. Most patients underwent surgical
      excision of the primary mass. With a median follow-up of 4 years (range, 1 mo to
      20 y), 87% of patients (63/72) were alive with no evidence of recurrence or
      metastatic disease. Local recurrence of the tumor was observed in 12% of patients
      (9 out of 72, multiple in 3 of them) at intervals between 6 months and 17 years
      after resection of the primary tumor. None of the patients developed tumor
      metastasis or died of disease. Identification of the neoplastic adipocytic
      component admixed with spindle cells, and recognition of the range of histologic
      appearances are key for the diagnosis of atypical spindle cell lipomatous tumor.
      Whereas the risk of metastatic dissemination is minimal, there is a non
      negligible risk for local recurrence (13%) which warrants surgical resection with
      clear margins whenever feasible.

PMID- 27879516
TI  - Performance of a Commercially Available MAL Antibody in the Diagnosis of Primary
      Mediastinal Large B-Cell Lymphoma.
AB  - Myelin and lymphocyte (MAL) protein has been previously reported as a highly
      specific marker for distinguishing primary mediastinal large B-cell lymphoma
      (PMBL) from diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS).
      However, there has not been a commercially available MAL antibody for
      immunohistochemistry. We identified a commercially available MAL monoclonal
      antibody and evaluated it by immunohistochemistry on 43 cases of PMBL and 63
      cases of DLBCL, NOS. We also compared this with a CD200 antibody that was
      previously reported useful in distinguishing PMBL and DLBCL, NOS. A threshold of
      10% positive tumor cells was used to determine positive protein expression. MAL
      was expressed in 72% cases of PMBL and 0% of cases of DLBCL, NOS
      (sensitivity=72%, specificity=100%). CD200 was expressed in 81% of PMBL cases and
      13% of DLBCL, NOS cases (sensitivity=81%, specificity=87%). To our knowledge,
      this is the first report on the utility of a commercially available MAL
      monoclonal antibody in the diagnosis of PMBL. There is a high specificity with
      good sensitivity in distinguishing PMBL from DLBCL, NOS, similar to previous
      studies with a noncommercial source. This antibody will likely prove useful in
      identifying cases of PMBL in routine practice.

PMID- 27879517
TI  - DUX4 Immunohistochemistry Is a Highly Sensitive and Specific Marker for CIC-DUX4
      Fusion-positive Round Cell Tumor.
AB  - The histologic differential diagnosis of pediatric and adult round cell tumors is
      vast and includes the recently recognized entity CIC-DUX4 fusion-positive round
      cell tumor. The diagnosis of CIC-DUX4 tumor can be suggested by light microscopic
      and immunohistochemical features, but currently, definitive diagnosis requires
      ancillary genetic testing such as conventional karyotyping, fluorescence in situ
      hybridization, or molecular methods. We sought to determine whether DUX4
      expression would serve as a fusion-specific immunohistochemical marker
      distinguishing CIC-DUX4 tumor from potential histologic mimics. A cohort of CIC
      DUX4 fusion-positive round cell tumors harboring t(4;19)(q35;q13) and
      t(10;19)(q26;q13) translocations was designed, with additional inclusion of a
      case with a translocation confirmed to involve the CIC gene without delineation
      of the partner. Round cell tumors with potentially overlapping histologic
      features were also collected. Staining with a monoclonal antibody raised against
      the C-terminus of the DUX4 protein was applied to all cases. DUX4
      immunohistochemistry exhibited diffuse, crisp, strong nuclear staining in all CIC
      DUX4 fusion-positive round cell tumors (5/5, 100% sensitivity), and exhibited
      negative staining in nuclei of all of the other tested round cell tumors,
      including 20 Ewing sarcomas, 1 Ewing-like sarcoma, 11 alveolar rhabdomyosarcomas,
      9 embryonal rhabdomyosarcomas, 12 synovial sarcomas, 7 desmoplastic small round
      cell tumors, 3 malignant rhabdoid tumors, 9 neuroblastomas, and 4 clear cell
      sarcomas (0/76, 100% specificity). Thus, in our experience, DUX4 immunostaining
      distinguishes CIC-DUX4 tumors from other round cell mimics. We recommend its use
      when CIC-DUX4 fusion-positive round cell tumor enters the histologic differential
      diagnosis.

PMID- 27879518
TI  - Three-month evaluation of strut healing using a novel optical coherence
      tomography analytical method following bioresorbable polymer everolimus-eluting
      stent implantation in humans: the TIMELESS study.
AB  - AIMS: Bioresorbable polymer drug-eluting stent technologies have been considered
      to have the potential to enhance vascular healing by reducing polymer exposure to
      the vessel wall, potentially allowing the earlier discontinuation of dual
      antiplatelet therapy. At present, the early vascular healing response to this
      type of technologies is still unclear. PATIENTS AND METHODS: The TIMELESS study
      is a multicenter, prospective, single-arm study that enrolled real-world patients
      undergoing percutaneous coronary intervention. All patients underwent Synergy
      stent implantation, which consists of a platinum-chromium platform coated with an
      ultra-thin abluminal bioabsorbable poly-D,L-lactide-co-glycolide polymer-eluting
      everolimus. RESULTS: A total of 37 patients were included in the study. The
      majority of the patients underwent percutaneous coronary intervention because of
      acute coronary syndromes. At 3 months, angiographic follow-up showed a percentage
      diameter of stenosis of 8.1+/-7.5% and an angiographic late loss of 0.03+/-0.24
      mm. In all analyzed struts, less than 1% of struts were definitely uncovered or
      covered with fibrin, 12.5% (5.0-18.5%) showed evidence of partial coverage, and
      the remaining (~85%) were fully covered. No stent thrombosis was observed up to
      12 months of clinical follow-up. CONCLUSION: In a real-world population, the
      implantation of a bioresorbable polymer drug-eluting stent resulted in almost
      complete strut coverage throughout the entire stent length at 3 months. The
      clinical implications for antiplatelet therapy and outcomes should be
      investigated further.

PMID- 27879519
TI  - Use of the Wattbike Cycle Ergometer for Attenuation of Bilateral Pedaling
      Asymmetry in Trained Cyclists.
AB  - Kell, DT and Greer, BK. Use of the Wattbike cycle ergometer for attenuation of
      bilateral pedaling asymmetry in trained cyclists. J Strength Cond Res 31(2): 468
      473, 2017-Experienced cyclists typically pedal with a 5-20% bilateral asymmetry
      in regards to power output. The aim of this study was to determine if visual
      feedback (VF) through the Wattbike cycle ergometer is an effective tool in
      reducing bilateral pedaling asymmetry in trained cyclists. Twelve subjects
      completed three 10-minute cycling trials on the Wattbike at a power output
      consistent with 60% V[Combining Dot Above]O2 peak. The 3 trials consisted of a
      baseline (BASE) trial in which cyclists pedaled without instruction, a conscious
      control (CC) trial during which cyclists attempted to pedal symmetrically, and
      another trial in which cyclists attempted to pedal symmetrically while using VF
      of their bilateral power outputs (%) through the Wattbike. Although the BASE
      trial was always performed first, the order of the CC and VF trials was
      counterbalanced to minimize the influence of the order effect. For the primary
      analysis, the Asymmetry Index percentages (AI%s) for the 3 trials were not
      significantly different (p > 0.05). However, secondary analysis of subjects who
      had baseline AI%s within the normal, reported range showed significantly
      decreased AI%s during the VF trial as compared with BASE (p <= 0.05). These
      results suggest that cyclists with normal AI%s can pedal more symmetrically while
      using VF of their asymmetry as opposed to merely attempting conscious correction
      without feedback. It is currently unknown whether adopting a more bilaterally
      symmetrical pedaling style will improve cycling performance or decrease injury
      rates in cyclists.

PMID- 27879521
TI  - Tibial nerve stimulation to inhibit the micturition reflex by an implantable
      wireless driver microstimulator in cats: Retracted.
AB  - BACKGROUND: Traditional tibial nerve stimulation (TNS) has been used to treat
      overactive bladder syndrome (OAB), but there are some shortcomings. Thus, a novel
      alternative is needed for the treatment of OAB. The study investigated the
      effects of a new type of tibial nerve microstimulator on the micturition reflex
      in cats. METHODS: An implantable wireless driver microstimulator was implanted
      around the tibial nerve in 9 alpha-chloralose anesthetized cats. Cystometry was
      performed by infusing 0.9% normal saline (NS) or 0.25% acetic acid (AA) through a
      urethral catheter. Multiple cystometrograms were performed before, during, and
      after TNS to determine the inhibitory effect of the microstimulator on the
      micturition reflex. RESULTS: TNS at 2 threshold (T) intensity significantly
      increased the bladder capacity (BC) during NS infusion. Bladder overactivity was
      irritated by the intravesical infusion of 0.25% AA, which significantly reduced
      the BC compared with the NS infusion. TNS at 2 T intensity suppressed AA-induced
      bladder overactivity and significantly increased the BC compared with the AA
      control. CONCLUSION: The implantable wireless driver tibial nerve microstimulator
      appears to be effective in inhibiting the micturition reflex during physiologic
      and pathologic conditions. The implantable wireless driver tibial nerve
      microstimulator could be used to treat OAB.

PMID- 27879522
TI  - A Systematic Review of Completeness of Reporting in Randomized Controlled Trials
      in Dermatologic Surgery: Adherence to CONSORT 2010 Recommendations.
AB  - BACKGROUND: Randomized controlled trials are the gold standard for comparing
      safety and effectiveness of surgical interventions. Reporting guidelines are
      available for conveying the results of such trials. OBJECTIVE: To assess
      adherence to standard reporting guidelines among randomized controlled trials in
      dermatologic surgery. MATERIALS AND METHODS: Systematic review. Data source was
      randomized controlled trials in the journal Dermatologic Surgery, per PubMed
      search, 1995 to 2014. Studies were appraised for the number of the 37 CONSORT
      2010 Checklist criteria reported in each. Analysis included comparison of
      reporting across 4 consecutive periods. RESULTS: Three hundred sixty-three
      studies were eligible. The mean number of items reported per study increased
      monotonically from 14.5 in 1995 to 1999 to 16.2 in 2002 to 2004, 17.7 in 2005 to
      2009, and 18.0 in 2010 to 2014 (p < .0001). A limitation was that study
      procedures may have been performed without being reported. CONCLUSION:
      Completeness of reporting in randomized controlled trials in dermatologic surgery
      has improved significantly during the preceding 2 decades. Some elements are
      still reported at lower rates.

PMID- 27879523
TI  - Prevalence of Multifocal Primary Hyperhidrosis and Symptom Severity Over Time:
      Results of a Targeted Survey.
AB  - BACKGROUND: There is a paucity of data on the prevalence of multifocal primary
      hyperhidrosis and changes in hyperhidrosis severity over time. OBJECTIVE: The
      goal of this study was to better understand multifocal primary hyperhidrosis,
      prevalence and distribution of hyperhidrosis by focal site, age of onset of
      symptoms by focal area, and change in hyperhidrosis severity over time and with
      seasons. MATERIALS AND METHODS: The International Hyperhidrosis Society, through
      an unrestricted research grant from Revance Therapeutics, conducted an online
      survey of registered visitors to its Web site. Participants identified as having
      "excessive sweating" and opted to participate in the survey (23 questions) after
      an e-mail invitation. RESULTS: The survey data illustrate that multifocal primary
      hyperhidrosis is more common than previously believed and that multifocal
      hyperhidrosis is more common than singular focal hyperhidrosis (81% of patients
      reported 3 or more focal hyperhidrotic sites). The data also show that sweating
      symptom severity does not improve with age but stays the same or gets worse and
      is "bothersome" throughout the year. CONCLUSION: Recognition of the chronic and
      multifocal nature of primary hyperhidrosis is useful for treating hyperhidrosis
      patients long term and illustrates a need for treatments or treatment
      combinations that are effective for multiple body areas.

PMID- 27879524
TI  - How We Do It: Digital Photomapping in Mohs Micrographic Surgery.

PMID- 27879525
TI  - Management of Patient Experience With ATX-101 (Deoxycholic Acid Injection) for
      Reduction of Submental Fat.

PMID- 27879526
TI  - Diagnostic Computed Tomography Coregistration With In-111-DTPA-Octreotide Single
      Photon Emission Tomography/Low-Dose Computed Tomography.
AB  - OBJECTIVES: In-111-DTPA-octreotide (OctreoScan) is still pivotal for
      neuroendocrine tumor imaging, despite the introduction of Ga-68-octreotide
      tracers. Low-dose computed tomography (LDCT) assists in the localization of SPECT
      findings but often results in uncertain interpretation. This retrospective study
      evaluates the impact of coregistration of In-111-DTPA-octreotide SPECT/LDCT with
      diagnostic CT on interpretation. METHODS: Thirty-five consecutive studies, in
      which coregistration was performed because of uncertain interpretation, were
      evaluated. Presence of somatostatin receptors was categorized retrospectively as
      definitely positive, probably positive, probably negative, or definitely negative
      with and without rigid registration with diagnostic CT, and possible added value
      of coregistration was evaluated. RESULTS: Coregistration was performed in 35
      studies. However, on subsequent reading, 4 SPECT/CTs yielded definite results and
      were omitted. Coregistration was helpful in 30 of the remaining 31 cases,
      changing reading to definitely positive (7) or to definitely negative (23). In 13
      of the 23 cases, diagnosis changed from probably positive to definitely negative.
      Coregistration contributed in 42 of 48 sites, with greatest benefit in the liver
      (13/14), pancreas (10/10), and lymph nodes (6/6). CONCLUSIONS: Coregistration is
      becoming increasingly easier and may be utilized when SPECT/LDCT is inconclusive.

PMID- 27879527
TI  - Support Vector Machines Model of Computed Tomography for Assessing Lymph Node
      Metastasis in Esophageal Cancer with Neoadjuvant Chemotherapy.
AB  - OBJECTIVE: The aim of this study was to diagnose lymph node metastasis of
      esophageal cancer by support vector machines model based on computed tomography.
      MATERIALS AND METHODS: A total of 131 esophageal cancer patients with
      preoperative chemotherapy and radical surgery were included. Various indicators
      (tumor thickness, tumor length, tumor CT value, total number of lymph nodes, and
      long axis and short axis sizes of largest lymph node) on CT images before and
      after neoadjuvant chemotherapy were recorded. A support vector machines model
      based on these CT indicators was built to predict lymph node metastasis. RESULTS:
      Support vector machines model diagnosed lymph node metastasis better than
      preoperative short axis size of largest lymph node on CT. The area under the
      receiver operating characteristic curves were 0.887 and 0.705, respectively.
      CONCLUSIONS: The support vector machine model of CT images can help diagnose
      lymph node metastasis in esophageal cancer with preoperative chemotherapy.

PMID- 27879528
TI  - Low-Tube Voltage Computed Tomography During Hepatic Arterial Phase: The Effect of
      Body Habitus on Image Quality.
AB  - PURPOSE: This study aimed to evaluate the impact of body habitus factors on image
      quality of low-tube voltage computed tomography (CT) during the hepatic arterial
      phase. MATERIALS AND METHODS: Ninety-seven patients (66 men, 31 women; age range,
      26-78 years) who underwent clinically indicated liver dynamic CT examination were
      enrolled in the study. Analysis with 80-kVp CT and intermediate tube current (277
      337 mA) was performed in the late hepatic arterial phase using a 320-detector row
      scanner with adaptive iterative dose reduction 3-dimensional reconstruction.
      Patient body habitus was measured using body weight (BW), body mass index (BMI),
      lateral width (LW) of the abdomen, and muscle volume (MV) of the abdominal wall.
      On hepatic arterial phase, the mean image noise and contrast-to-noise ratio (CNR)
      for the aorta and liver were assessed. The correlations between body habitus
      factors and image quality parameters were evaluated. RESULTS: In all patients, MV
      showed the strongest correlation with image noise, followed by BW and LW (r =
      0.684, 0.570, and 0.555, respectively). The BMI showed the fourth strongest
      correlation with image noise among all body habitus factors (r = 0.377). With
      respect to CNR of the aorta, MV and BW showed the strongest inverse correlation
      (r = -0.590 and -0.600, respectively), followed by LW and BMI (r = -0.557 and 
      0.423, respectively). Regarding the CNR of the liver, MV showed the strongest
      inverse correlation (r = -0.279), although the correlation efficiency was weak
      compared with other correlations. CONCLUSIONS: Among various body habitus
      factors, MV showed the strongest association with image noise and CNR in the
      hepatic arterial phase using 80-kVp CT.

PMID- 27879529
TI  - Morphometric Study of the Vestibular Aqueduct in Patients With Enlarged
      Vestibular Aqueduct.
AB  - OBJECTIVE: To test whether there are significant differences in the morphologic
      features of the enlarged vestibular aqueduct (EVA) and its anatomic relationships
      with adjacent structures between EVA patients with and without other inner ear
      malformations. METHODS: The morphology of vestibular aqueduct, volume of
      vestibule, and anatomic location of facial nerve (FN) were compared among 3
      groups. Group A, 18 control subjects; group B, 32 EVA patients without other
      inner ear malformations; group C, 14 EVA patients with other inner ear
      malformations. RESULTS: The isthmus of the aqueduct and vestibular volume in
      group C were larger than those in group B (P < 0.05). Positive correlations were
      identified between the length of the aqueduct and the vestibular volume in groups
      B and C. The vertical FN segment in group C located more anteriorly than that in
      groups A and B (P < 0.05). CONCLUSIONS: Compared with EVA patients without other
      inner ear malformations, the aqueduct, and vestibule in EVA patients with other
      inner ear malformations are larger, the vertical FN segment locates more
      anteriorly.

PMID- 27879530
TI  - Transaortic Edge-to-Edge Repair for Functional Mitral Regurgitation During Aortic
      Valve Replacement: A 13-Year Experience.
AB  - OBJECTIVE: The study evaluated the feasibility of a transaortic edge-to-edge
      mitral valve repair (Alfieri stitch) for moderate or greater (>=2+) functional
      mitral regurgitation (MR) in high-risk patients undergoing aortic valve
      replacement. METHODS: We retrospectively evaluated 40 consecutive patients who
      underwent aortic valve replacement combined with a transaortic edge-to-edge
      mitral valve repair for 2+ or greater functional MR, between February 2002 and
      April 2015. The MR was graded semiquantitatively as 0 (trace/none), mild (1+),
      moderate (2+), or moderate to severe (3-4+). RESULTS: Thirty-two patients had
      aortic stenosis, and eight had aortic regurgitation. The mean +/- standard
      deviation (SD) age was 77.5 +/- 5 years, 34 (85%) were male, and the mean +/- SD
      EuroSCORE II was 14.3% +/- 12.9. At a median follow-up of 1 month (interquartile
      range, 0.75-10), there were significant improvements in preoperative versus
      postoperative median MR grade (3+ vs 1+, P < 0.001), mean left ventricular
      ejection fraction (34% vs 41%, P = 0.018), left ventricular end-diastolic
      diameter (54 vs 49 mm, P = 0.005), and pulmonary artery systolic pressure (49 vs
      35 mm Hg, P < 0.001). Persistent 3 to 4+ MR occurred in two patients (5%). In 12
      patients with at least 6-month follow-up (mean +/- SD, 18 +/- 11 months), a
      sustained improvement in all echocardiographic parameters was observed, with
      persistent 3 to 4+ MR occurring in one patient (8.3%). Actuarial survival at 1,
      3, and 4.5 years was 82% +/- 6, 71% +/- 8, and 65% +/- 10, respectively.
      CONCLUSIONS: A transaortic edge-to-edge repair for 2+ or greater functional MR
      can be safely performed during aortic valve replacement and is associated with
      improvements in MR grade, left ventricular remodeling, and pulmonary
      hemodynamics.

PMID- 27879531
TI  - B-type Natriuretic Peptide Predicts Morbidity and Long-Term Mortality in Coronary
      Artery Bypass Grafting and Valve Surgery.
AB  - OBJECTIVE: To assess whether B-type natriuretic peptide (BNP) levels are a useful
      predictor of morbidity and mortality as well as long-term survival in patients
      after coronary artery bypass grafting (CABG) and valve surgery. METHODS: A
      retrospective review of CABG and/or valve surgery patients from 2012 to 2015 at a
      single center was conducted. A total of 432 patients were identified (CABG, 295
      patients; valve, 82 patients; and CABG + valve, 55 patients). B-type natriuretic
      peptide levels were divided into quartiles (Q1-Q4). Mortality data were available
      for up to 3.4 years after surgery. RESULTS: B-type natriuretic peptide quartile
      was independently associated with any complication on multivariate analysis.
      Patients in Q4 were at highest risk (adjusted odds ratio, 3.81; P = 0.047 vs Q1).
      There was a significant association between BNP quartile and time to death (log
      rank chi, 8.30; P = 0.04) with greatest association 9 months postoperatively. B
      type natriuretic peptide quartile was significantly associated with time to death
      in Cox regression in Q2 (hazard ratio [HR], 3.73 (1.04-13.44); P = 0.044) and Q4
      (HR, 4.33 (1.14-16.44); P = 0.031). Q3 also had a higher risk of death (HR, 3.5
      vs Q1); however, this was only significant at a trend level (P = 0.06). Using a
      risk model generated from logistic regression, we determined that the highest
      risk group had relative risk of complications 30 times higher than the lowest
      risk group. CONCLUSIONS: B-type natriuretic peptide levels are an independent
      predictor of morbidity after CABG and/or valve surgery regardless of type of
      procedure or on/off bypass usage. B-type natriuretic peptide levels also
      correlate with time to death, highlighting the need for sustained follow-up and
      heart failure management to improve survival in patients with elevated BNP levels
      presenting for all cardiac surgery.

PMID- 27879532
TI  - Myocardial Protection and Financial Considerations of Custodiol Cardioplegia in
      Minimally Invasive and Open Valve Surgery.
AB  - OBJECTIVE: Single-dose antegrade crystalloid cardioplegia with Custodiol-HTK
      (histidine-tryptophan-ketoglutarate) has been used for many years. Its safety and
      efficacy were established in experimental and clinical studies. It is beneficial
      in complex valve surgery because it provides a long period of myocardial
      protection with a single dose. Thus, valve procedures (minimally invasive or
      open) can be performed with limited interruption. The aim of this study is to
      compare the use of Custodiol-HTK cardioplegia with traditional blood cardioplegia
      in patients undergoing minimally invasive and open valve surgery. METHODS: A
      single-institution, retrospective case-control review was performed on patients
      who underwent valve surgery in Lee Memorial Health System at either HealthPark
      Medical Center or Gulf Coast Medical Center from July 1, 2011, through March 7,
      2015. A total of 181 valve cases (aortic or mitral) performed using Custodiol-HTK
      cardioplegia were compared with 181 cases performed with traditional blood
      cardioplegia. Each group had an equal distribution of minimally invasive and open
      valve cases. Right chest thoracotomy or partial sternotomy was performed on
      minimally invasive valve cases. Demographics, perioperative data, clinical
      outcomes, and financial data were collected and analyzed. RESULTS: Patient
      outcomes were superior in the Custodiol-HTK cardioplegia group for blood
      transfusion, stroke, and hospital readmission within 30 days (P < 0.05). No
      statistical differences were observed in the other outcomes categories. Hospital
      charges were reduced on average by $3013 per patient when using Custodiol-HTK
      cardioplegia. CONCLUSIONS: Use of Custodiol-HTK cardioplegia is safe and cost
      effective when compared with traditional repetitive blood cardioplegia in
      patients undergoing minimally invasive and open valve surgery.

PMID- 27879533
TI  - The AngioVac Device: Understanding the Failures on the Road to Success.
AB  - OBJECTIVE: Current percutaneous thromboembolectomy techniques may obviate
      surgical intervention in high-risk patients with iliocaval thrombus or thrombus
      of the right side of the heart, but typically require thrombus fragmentation and
      thrombolysis with associated bleeding and thromboembolic complications. The
      AngioVac (Angiodynamics, Latham, NY USA) device uses a percutaneous venovenous
      bypass circuit to aspirate intact thrombus. A review of the literature was
      performed with regard to the AngioVac device to determine the factors correlating
      with successful thrombus extraction. METHODS: A literature search was performed
      with regard to use of the AngioVac device using the PubMed database. A meta
      analysis was not performed given the small size and lack of statistical analysis
      of the individual reports included. RESULTS: Twenty-three reports describing 57
      procedures in 56 patients were analyzed. Indications for thrombectomy included
      iliocaval thrombus in 53% (30), thrombus of the right side of the heart, in 49%
      (28), pulmonary embolus in 14% (8), and upper extremity venous/Glenn shunt
      thrombosis in 7% (4). The complete success rate, defined as removal of all
      thrombus, was 75% (43), with an 11% (6) partial success rate. In 14% (8) of
      cases, minimal or no thrombus was retrieved. When analyzed by indication,
      iliocaval thrombus and thrombus of the right side of the heart demonstrated 87%
      (26) and 82% (23) complete success rates, respectively. Pulmonary embolus
      demonstrated a significantly lower success rate at 12.5% [1; (P < .001)].
      Complications occurred in 12% (7), including six hematomas and one
      retroperitoneal bleed. CONCLUSIONS: The AngioVac device offers an excellent
      alternative to surgical thrombectomy for patients presenting with iliocaval or
      intracardiac thrombus, with success rates of more than 80%, although it seems
      that pulmonary emboli are less amenable. Appropriate patient selection can lead
      to improved outcomes. Larger numbers are needed to make more definite
      conclusions.

PMID- 27879534
TI  - Physician-provided prehospital critical care, effect on patient physiology
      dynamics and on-scene time.
AB  - INTRODUCTION: Improved physiologic status can be seen as a surrogate measure of
      improved outcome and a field-friendly prognostic model such as the Mainz
      Emergency Evaluation Score (MEES) could quantify the effect on physiological
      response. We aim to examine the dynamic physiological profile as measured by this
      score on patients managed by physician-manned helicopter emergency medical
      services and how this profile was related to on-scene time expenditure and
      critical care interventions. MATERIALS AND METHODS: Data including patient
      characteristics, physiological data, and description of diagnostic and
      therapeutic interventions were prospectively collected over two 14-day periods,
      summer and winter, at six participating Norwegian bases. The MEES score was
      utilized to examine the difference between a score measured at first patient
      contact (MEES 1) and end-of-care (MEES 2), (MEES 2-MEES 1=[INCREMENT]MEES).
      RESULTS: A total of 240 primary missions with patient-on-scene form the basis of
      the study. In total, 43% were considered severely ill or injured, of whom 59%
      were medical patients. Twenty-nine percent were severely deranged
      physiologically. The most common advanced procedure performed was advanced airway
      management (15%), followed by defibrillation (8.8%). Using [INCREMENT]MEES as an
      indicator, 1% deteriorated under care, whereas 66% remained unchanged and 33%
      showed an improvement in their physiological status. With increasing on-scene
      time, fewer patients deteriorated and a greater proportion of patients improved.
      CONCLUSION: Restoring deranged physiology remains a mantra for all critical care
      practitioners. We have shown that this is also possible in the prehospital
      context, even when prolonging on-scene time, and after initiating advanced
      procedures.

PMID- 27879535
TI  - Agreement between arterial and venous lactate in emergency department patients: a
      prospective study of 157 consecutive patients.
AB  - INTRODUCTION: In the emergency department (ED), lactate is routinely used for
      risk stratification. Whether venous or arterial lactate measured on blood gas is
      interchangeable is not known. We hypothesized that venous lactate can be used
      instead of arterial lactate for the evaluation of acute patients in the ED.
      PATIENTS AND METHODS: This was a prospective single-center study. All patients
      requiring a lactate measurement were enrolled and we simultaneously drew arterial
      and venous blood. We followed up all patients to hospital discharge. Our primary
      aim was to evaluate agreements between the two measurements using Bland and
      Altman plots with the report of bias (mean difference) and limits of agreements.
      We also aimed to determine the rate of misclassification (defined as one
      measurement<1.8 mmol/l and the other>2.2). Our secondary aim was to evaluate
      their respective prognostic value to predict in-hospital death or admission in
      the ICU longer than 72 h. RESULTS: The mean age of the 132 analyzed patients was
      62 years (SD: 18 years), and 59% were men. The mean difference (bias) between
      arterial and venous lactate was -0.6 mmol/l (limits of agreement: -1.7 to 0.6
      mmol/l). The rate of misclassification was 8% (95% confidence interval: 3-2%).
      Both methods present similar performances for the prediction of poor outcomes,
      with an area under the receiving operator characteristic curves of 0.67 for both.
      Results were similar when focused only on septic patients. CONCLUSION: Venous and
      arterial lactates do not agree well, and there is a high misclassification rate.
      Venous lactate does not appear to be interchangeable with arterial sampling.

PMID- 27879536
TI  - Mental health promotion for junior physicians working in emergency medicine:
      evaluation of a pilot study.
AB  - OBJECTIVES: Work-related stress is highly prevalent among physicians working in
      emergency medicine. Mental health promotion interventions offer the chance to
      strengthen physicians' health, work ability, and performance. The aim of this
      study was to implement and evaluate a mental health promotion program for junior
      physicians working in emergency medicine. METHODS: In total, 70 junior physicians
      working in emergency medicine were randomized to either the mental health
      promotion program (n=35) or a waitlist control arm (n=35). The training involved
      90-min sessions over a time period of 3 months. The primary outcome was perceived
      stress. The secondary outcomes included emotional exhaustion, emotion regulation,
      work engagement, and job satisfaction. Self-report assessments for both groups
      were scheduled at baseline, after the training, after 12 weeks, and 6 months.
      RESULTS: The intervention group showed a highly significant reduction in
      perceived stress and emotional exhaustion from baseline to all follow-up time
      points, with no similar effects found in the comparison group. The benefit of the
      mental health promotion program was also evident in terms of improved emotion
      regulation skills, job satisfaction, and work engagement. Participating
      physicians evaluated the training with high scores for design, content, received
      outcome, and overall satisfaction. CONCLUSION: The results suggest that this
      health promotion program is a promising intervention to strengthen mental health
      and reduce perceived work stress. It is suitable for implementation as a group
      training program for junior physicians working in emergency medicine. Comparable
      interventions should be pursued further as a valuable supportive offer by
      hospital management.

PMID- 27879537
TI  - Rhabdomyosarcoma of the Breast in Adolescent and Young Adult (AYA) Women.
AB  - Soft tissue sarcoma constitutes 8% of all tumors in adolescent and young adults
      (AYA), with rhabdomyosarcoma (RMS) accounting for 5.2% to 6.5% of the soft tissue
      sarcoma total within this group. AYAs have a higher propensity for metastasis and
      inferior outcomes. Metastases to the breast have been reported in ~3% to 6% of
      RMS cases. A review of our hospital's tumor registry identified cases of RMS
      diagnosed between January 1, 2004 and December 31, 2013. A total of 46 patients
      with RMS were identified, having a mean age of 12.5 years (range, 1 to 49 y).
      There were 26 males (57%) and 20 females (43%). Eighteen patients (39%) were
      AYAs, including 10 women. Four patients (8.7%) were identified with breast
      involvement, all of whom were AYA females. Treatment modalities included
      chemotherapy, surgical resection, and radiation. One patient is a long-term
      survivor. Although RMS is uncommon in AYAs, breast involvement occurs almost
      exclusively in AYA women and is associated with alveolar histology, metastatic
      disease, and poor outcomes. In total, 4/10 of all AYA females had breast
      involvement. Routine examination or imaging of the breasts in AYAs with RMS is
      not currently standard practice at diagnosis or follow-up, but this analysis
      suggests it should be considered in female AYA patients.

PMID- 27879538
TI  - Efficacy of Ifosfamide-Cisplatin-Etoposide (ICE) Chemotherapy for a CNS Germinoma
      in a Child With Down Syndrome.
AB  - Intracranial germ cell tumor is sometimes associated with Down syndrome; however,
      no optimal treatment has been developed due to the high risk of recurrence and
      treatment-related mortality. Here, we report on a patient with an intracranial
      germinoma in the bilateral basal ganglia. The patient received 3 courses of
      ifosfamide-cisplatin-etoposide in combination with whole-brain irradiation (24
      Gy), with no serious complications. The patient is alive and disease free 16
      months after the initial diagnosis. This regimen is a feasible treatment for
      intracranial germ cell tumor associated with Down syndrome, although careful
      attention must be paid to the increased risk for severe infection.

PMID- 27879540
TI  - Severe Hemolytic Anemia Following Intravenous Immunoglobulin in an Infant With
      Kawasaki Disease.
AB  - Severe hemolytic anemia (HA) is an uncommon adverse reaction of intravenous
      immunoglobulin (IVIg) administration. Previous reports assume that antibodies
      contained in IVIg preparations are the cause of hemolysis. We report a 10-month
      old infant with Kawasaki disease who was treated with high-dose IVIg and
      developed severe HA. The patient's Rh blood type was D+C+c+E-e+. He developed
      anti-C and anti-e antibodies following treatment with IVIg, and, after
      considering all possible causes of hemolysis, we concluded that this was a case
      of autoimmune HA induced by immunoglobulin treatment. The hyperinflammatory
      condition associated with Kawasaki disease may have contributed to the severity
      of anemia.

PMID- 27879541
TI  - Ethical Barriers in Adolescent Oncofertility Counseling.
AB  - Adult survivors of pediatric cancers are at substantial risk for infertility.
      Oncofertility is an emerging field in medicine that has focused on the fertility
      preservation of these patients. As the field continues to develop, there are
      several areas in which our practice has improved. However, several ethical
      concerns still exist involving beneficence, nonmaleficence, informed consent,
      adolescent assent, and posthumous use of reproductive tissues. Because the field
      is still developing, great disparities exist in available options depending on
      age, ability to pay, and geographic location. Such discrepancies in access may
      lead to health disparities in the adolescent patient population. As the science
      continues to make future fertility more feasible, the ethical questions will
      continue to be more complex. The purpose of this article is to review some of the
      developments regarding oncoferility and address future directions for research
      and inquiry in specific areas.

PMID- 27879539
TI  - Clinically Mild Encephalitis/Encephalopathy With a Reversible Splenial Lesion
      Accompanied by Epstein-Barr Virus Hemophagocytic Lymphohistiocytosis: A Case
      Report and Review of the Literature.
AB  - Central nervous system involvement in hemophagocytic lymphohistiocytosis (HLH) is
      associated with a poor outcome. For such patients, it is unknown whether more
      aggressive therapies, such as intrathecal methotrexate or hydrocortisone, are
      inevitably required. We present a very rare case of 3-year-old Japanese girl who
      developed mild encephalitis/encephalopathy with a reversible splenial lesion,
      accompanied by Epstein-Barr virus-associated HLH, and review previous similar
      reports. Our case and previous reports suggest that mild
      encephalitis/encephalopathy with a reversible splenial lesion accompanied by
      Epstein-Barr virus-associated HLH has a relatively good prognosis, even in the
      absence of intrathecal treatments.

PMID- 27879542
TI  - Central Nervous System Symptoms Due to Transient Methemoglobinemia in a Child
      With G6PD Deficiency.
AB  - The authors herein report a 5-year-old child who presented with massive
      hemolysis, irritability, and cyanosis. The final diagnosis was glucose-6
      phosphate dehydrogenase deficiency with associated central nervous system
      symptoms probably because of concomitantly acquired methemoglobinemia following
      oxidant drug exposure. The associated acute-onset anemia would have contributed
      to the development of cerebral anoxia-related seizures and encephalopathy.

PMID- 27879544
TI  - Immune Hemolytic Anemia (Paroxysmal Cold Hemoglobinuria) Preceding Burkitt
      Lymphoma in a 12-Year-Old Child.
AB  - Autoimmune hemolytic anemia (AIHA) in childhood, including paroxysmal cold
      hemoglobinuria, is an uncommon, potentially life-threatening disorder. AIHA is a
      recognized complication of several varieties of lymphoproliferative disorders,
      including high-grade B-cell lymphoma, but it has not been associated with Burkitt
      lymphoma in people without an underlying immunodeficiency. When AIHA occurs in
      association with lymphoproliferative disorders, it may precede or accompany the
      diagnosis of malignant disease or herald relapse. We report a novel case of a
      previously healthy child diagnosed with paroxysmal cold hemoglobinuria 14 months
      preceding the development of Burkitt lymphoma.

PMID- 27879543
TI  - Enzymopenic Congenital Methemoglobinemia in Children of the Republic of Sakha
      (Yakutia).
AB  - Type I congenital methemoglobinemia is an autosomal recessive disorder. A high
      frequency of congenital methemoglobinemia has been reported among Native
      Americans inhabiting the Yukon-Kuskokwim Delta. Other rare cases of congenital
      methemoglobinemia of types I and II have been reported in Japan and other
      countries. In Russia-namely, in Yakutia-a high frequency of type I congenital
      methemoglobinemia has been reported. In 2009, the Consultation Polyclinic of the
      Pediatric Center in Yakutsk city established a registry of children with
      congenital methemoglobinemia. In total, 43 patients were registered between 2005
      and 2009. The median methemoglobin level was 13.5% (ranging between 4.2% and
      33.9%) and physical examination revealed cyanosis of the skin and mucus
      membranes. There were significant positive relationships between percentage of
      methemoglobin and erythrocyte count, hemoglobin concentration, and hematocrit
      among male patients, consistent with an upregulation of the hypoxic response. The
      prevalence per 100,000 children ranged from 12.7 to 47.0 in 3 geographic regions
      of Yakutia. Further research is needed to clarify the clinical consequences of
      congenital methemoglobinemia in the children of Yakutia and the reasons for the
      high variability in the prevalence of the condition.

PMID- 27879545
TI  - Epstein-Barr Virus-associated Mucocutaneous Ulcer in a Patient With T-Cell Acute
      Lymphoblastic Leukemia: Importance of Accurate Diagnosis and Conservative
      Management.
AB  - Epstein-Barr virus-associated mucocutaneous ulcer (EBV-MCU) is a recently
      characterized entity that falls under the spectrum of EBV-lymphoproliferative
      disorders. First described in 2010 by Dojcinov et al, it is an EBV-driven
      localized proliferation of B cells, occurring in mucocutaneous tissues including
      the skin, the oropharynx, and the gastrointestinal tract of immunosuppressed
      patients in the absence of an intact T-cell repertoire. Typically, it has been
      described in elderly patients with age-related immunosenescence and patients who
      are on immunosuppressive therapy. However, only 2 cases have been reported in
      pediatric, adolescent, and young adult age groups, with all these patients
      manifesting after solid organ transplant. To the best of our knowledge there are
      no case reports of EBV-MCU occurring in association with hematologic malignancy.
      Here, we present a case of EBV-MCU in a young adult patient with T-cell acute
      lymphoblastic leukemia. Our report serves to promote awareness among clinicians
      regarding this newly described and extremely rare clinical entity in young
      immunosuppressed patients. In addition, we highlight the importance of accurate
      diagnosis to prevent overtreatment of this indolent, often self-resolving disease
      that has a significant clinicopathologic overlap with other aggressive forms of
      EBV-lymphoproliferative disorders that require more intensive therapy.

PMID- 27879546
TI  - Early Lymphocyte Recovery and Outcome in Osteosarcoma.
AB  - BACKGROUND: Early lymphocyte recovery following chemotherapy has been associated
      with improved outcome in many cancers, including in one small study of
      osteosarcoma patients. MATERIALS AND METHODS: To confirm this finding, we
      retrospectively reviewed data from 53 patients with newly diagnosed osteosarcoma
      who had blood counts on day 14 (+/-1 d) following the first cycle of cisplatin
      and doxorubicin. RESULTS: The median absolute lymphocyte count (ALC) 14 days
      after starting the first cycle of chemotherapy (ALC-14) was 1990 cells/MUL
      (range: 600 to 6470). For 32 patients with an ALC-14>=1800 cells/MUL, the 5-year
      progression-free survival (PFS) was 69%, compared with 33% for patients with an
      ALC-14 of <1800 cell/MUL (P=0.036). In multivariable analysis of factors
      including age, sex, metastatic disease, and favorable histologic response to
      induction chemotherapy, ALC-14 was significantly associated with PFS (P=0.0081)
      and overall survival (P=0.0131). The use of ALC-14 appears to further stratify
      PFS and overall survival among patients when grouped by histologic response.
      CONCLUSIONS: We confirmed that early lymphocyte recovery was associated with
      outcome in pediatric osteosarcoma. Although presumably reflecting immune-mediated
      tumor control, the precise mechanism for this is unclear. Further study of
      peripheral blood lymphocyte subpopulations in prospectively treated patients is
      underway.

PMID- 27879547
TI  - Hyperferritinemia in Pediatric Acute Lymphoblastic Leukemia: What Does it Mean?

PMID- 27879548
TI  - Switching L-dopa Therapy from Pulsatile to Pulse Administration Reduces Motor
      Complications in Parkinson's Disease.
AB  - OBJECTIVE: To evaluate the severity of wearing-off and dyskinesia in patients
      with complicated Parkinson disease (PD) after switching L-dopa oral therapy from
      a "pulsatile" administration, consisting in intermittent multiple daily small
      doses of the drug, to a "pulse" administration, consisting in standard oral doses
      given at specific interdose intervals. METHODS: Thirty-four PD patients with
      motor complications were monitored twice with standardized waking day motor
      status evaluations using the Unified Parkinson Disease Rating Scale-Motor
      Examination (UPDRS-ME) and the Abnormal Involuntary Movement Scale (AIMS) after
      switching L-dopa administration modality from "pulsatile" to "pulse." To quantify
      predictable motor fluctuations, a Wearing Off Index was computed based on changes
      in treatment response magnitude. RESULTS: On the whole, after switching from
      "pulsatile" to "pulse" administration, there was a reduction in number of L-dopa
      daily doses and an increase in the amount of the dosage of the single doses, AIMS
      maximum score decreased without increasing motor disability. More specifically,
      in predominant fluctuating patients, there was a significant reduction in UPDRS
      ME average score as well as in Wearing Off Index. In predominant dyskinetic
      patients, there was a significant reduction in average and maximum AIMS scores
      with no changes in average and maximum UPDRS-ME scores. CONCLUSIONS: Switching L
      dopa therapy from "pulsatile" to "pulse" modality may reduce the severity of
      wearing-off and dyskinesia in complicated PD.

PMID- 27879549
TI  - Fingolimod Use for the Treatment of Multiple Sclerosis in a Clinical Practice
      Setting in Madrid.
AB  - OBJECTIVE: To assess the effectiveness and safety of fingolimod use in a Spanish
      clinical practice setting. METHODS: Retrospective study with multiple sclerosis
      patients who received at least 1 fingolimod dose between January 2004 and January
      2015. Effectiveness and safety data were collected during the entire treatment of
      each patient. Analysis was performed for the total population and stratified
      according to prior treatment, sex, and age at treatment initiation. RESULTS: A
      total of 167 patients were included, 50.9% had prior immunomodulator use, 33.5%
      natalizumab use, and 15.6% were naive patients. The annual relapse rate (ARR)
      decreased for the total population at month 12 (62%) and month 24 (84%) (P <
      0.0001, in both cases); for naive patients (P < 0.05) and patients with prior
      immunomodulator use (P < 0.0001); for patients with prior natalizumab use, the
      ARR kept low after treatment initiation (0.23). After 24 months, the proportion
      of relapse-free patients was 70% or greater and disability progression-free
      patients was 80% or greater. No significant differences were observed when the
      results were compared by prior treatment, sex, or age. Thirty-two patients
      (19.2%) reported adverse drug reactions and 9.6% discontinued: 4.8% due to
      adverse drug reactions and 4.8% for lack of effectiveness. CONCLUSIONS: The
      results support fingolimod use due to clinical effectiveness, tolerability, and
      ease of administration.

PMID- 27879550
TI  - Successful Treatment of Brachial Plexopathy Due to Herpes Zoster Infection With
      Intravenous Immunoglobulin.
AB  - OBJECTIVE: The aim of this study was to report the case of a male patient with
      Parkinson disease who developed brachial plexopathy (BP) due to varicella-zoster
      virus, which was successfully treated with human immunoglobulin. METHOD: We
      report the case of a 75-year-old male subject with a diagnosis of Parkinson
      disease who came to our hospital complaining of pain, skin lesions, and strength
      loss in his right arm during the past 2 months. Physical examination revealed
      vesicular rash compatible with varicella-zoster virus lesions. Nerve conduction
      studies and magnetic resonance imaging of the brachial plexus showed inflammatory
      changes at that level. A trial with oral valacyclovir followed by intravenous
      methylprednisolone bolus was administered without further response. However,
      human intravenous immunoglobulin resulted in complete recovery of the symptoms.
      CONCLUSIONS: Human immunoglobulin is effective in BP due to zoster infection and
      must be considered if standard treatment fails. To the best of our knowledge,
      this is the first report of BP associated to zoster infection successfully
      treated with intravenous immunoglobulin.

PMID- 27879551
TI  - No Superiority of Treatment With Osmotic Controlled-Release Oral Delivery System
      Methylphenidate Over Short/Medium-Acting Methylphenidate Preparations in the Rate
      and Timing of Injuries in Children With Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVES: Methylphenidate (MPH) treatment in patients with attention
      deficit/hyperactivity disorder (ADHD) is reported to reduce the risk for
      injuries. In the present study, the rate and timing of injuries were compared
      among the various MPH preparations (4 and 6-8 vs 12 hour-acting) in children with
      ADHD. METHODS: This real-world retrospective study covered the years 2011 to
      2013. Participants included 2042 youngsters (aged 4-18 years, 13.01 +/- 3.2
      years; 71.8% males and 28.2% females) diagnosed with ADHD according to the
      International Statistical Classification of Diseases, 10th Revision criteria and
      treated with various MPH preparations. They were divided into 2 groups by their
      treatment preparation as follows: MPH-immediate release (MPH-IR)-4 hour-acting
      pooled with MPH-slow release/long-acting (MPH-SR/LA)- 6 to 8 hour-acting versus
      osmotic controlled-release oral delivery system-MPH (OROS-MPH; Concerta)-12 hour
      acting that consisted of pooling of OROS-MPH only and OROS-MPH combined with the
      other MPH preparations. The monthly rates of injury, specifically, late injury
      (occurrence between 4:00 p.m. to midnight) and for multiple injuries, the time
      interval between injuries, were assessed. RESULTS: No significant differences in
      monthly rate of nonfatal injuries were found between OROS-MPH with or without 4/6
      to 8 hour-acting MPH-formulations versus only 4/6 to 8 hour-acting MPH
      preparations (P = 0.53). Neither were differences found in the between-injury
      time interval (P = 0.83) or in late-injury-rates (P = 0.37) between those groups.
      CONCLUSIONS: This real-world-naturalistic study in the community demonstrates
      that, in ADHD pediatric populations, OROS-MPH preparation is not superior to
      short/medium-acting (4/6-8 hours) MPH preparations regarding the rate and timing
      of injuries.

PMID- 27879552
TI  - The Impact of Complicated Grief on Diurnal Cortisol Levels Two Years After Loss:
      A Population-Based Study.
AB  - OBJECTIVE: Few studies have focused on the effect of complicated grief-unresolved
      and prolonged grief-on the neuroendocrine systems. The present study examined the
      association of complicated grief and normal grief with the diurnal cortisol
      patterns in a large population-based study. METHODS: This study was set in the
      Rotterdam Study and comprised 2084 persons aged older than 55 years (mean [SD]
      age, 64.9 [5.5] years). Participants were assessed with the Complicated Grief
      Inventory and classified into no grief (n = 1922), normal grief (n = 131), or
      complicated grief (n = 31) if they experienced the loss in the past 2 years.
      Saliva samples were collected to measure cortisol levels. Morning cortisol and
      summary measures (area under the curve and the slope) were studied to account for
      the diurnal pattern of cortisol. Persons with depressive disorders were excluded,
      and analyses were additionally adjusted for depressive symptoms. RESULTS:
      Compared to normal grievers, participants with complicated grief showed lower
      levels of morning cortisol (11.26 vs 15.51 nmol/L; difference, -4.24; 95%
      confidence interval [CI] = -7.87 to -0.62; p = .022), and lower levels of overall
      diurnal cortisol (6.89 vs 8.98 nmol/L; difference, -2.09; 95% CI = -3.81 to 
      0.37; p = .017). No difference was observed in slope between both groups.
      Participants with complicated grief also showed lower levels of morning cortisol
      than the nongrievers (11.26 vs 14.71; difference, -3.46; 95% CI = -6.78 to -0.13;
      p = .042). In contrast, cortisol secretion patterns did not differ between
      persons with normal grief and nongrieving controls. CONCLUSIONS: Participants
      with complicated grief showed low levels of morning cortisol and low overall
      diurnal cortisol levels characteristic for a chronic stress reaction.

PMID- 27879553
TI  - ACUTE VISION LOSS AS THE ONLY SIGN OF LEUKEMIA RELAPSE.
AB  - PURPOSE: To report a case of unilateral exudative retinal detachment as the sole
      presentation of relapsing B-type lymphoblastic leukemia in a 35-year-old man
      after 3 years of remission. METHODS: Case report. RESULTS: A 35-year-old man in
      complete remission of high-risk type B acute lymphoblastic leukemia (ALL-B)
      presented with acute vision loss in his left eye. Exudative retinal detachment
      was diagnosed at initial evaluation. Hematological and ocular studies were
      performed. Although there was no evidence of blood, cerebrospinal fluid, or bone
      marrow disease relapse, transvitreal retinochoroidal cytology identified the
      infiltration of lymphoblastic leukemic B cells with t(12:21) translocation as the
      only sign of relapsing ALL-B. CONCLUSION: At first sign of vision loss or ocular
      symptoms in a patient with a history of lymphoblastic leukemia, and regardless of
      the hematological findings, exhaustive ophthalmologic exploration and ocular
      biopsy should be performed without delay-this being crucial for clinical decision
      making because a prompt diagnosis improves the chances of survival.

PMID- 27879555
TI  - Safety and Immunogenicity of DTaP5-IPV Compared With DTaP5 Plus IPV as the Fifth
      Dose in Children 4-6 Years of Age.
AB  - BACKGROUND: Immunogenicity and safety of stand-alone diphtheria, tetanus toxoid,
      5-component acellular pertussis vaccine adsorbed, inactivated poliovirus (IPV)
      combination vaccine (DTaP5-IPV) was compared with separate DTaP5 plus IPV
      vaccines as fifth dose in children 4-6 years of age. METHODS: In this phase III,
      controlled, multicenter, randomized, open-label study, participants were
      randomized to DTaP5-IPV plus measles/mumps/rubella (MMR) and varicella virus
      (VZV) vaccines (group 1; N = 324), DTaP5+IPV with MMR and VZV (group 2; N = 327),
      DTaP5-IPV with/without MMR/VZV (group 3; N = 2419) or DTaP5+IPV with/without
      MMR/VZV (group 4; N = 302). Immunogenicity endpoints (groups 1 and 2) included
      booster response rates and antibody geometric mean concentrations (GMCs).
      Noninferiority of DTaP5-IPV to DTaP5+IPV was evaluated based on differences
      (groups 1 and 2) in booster rates and postvaccination GMC ratios. Safety
      endpoints (all groups) included all adverse events. RESULTS: Noninferiority of
      DTaP5-IPV compared with DTaP5+IPV for all antigens was achieved. Booster rate
      differences were 5.4% for pertussis toxoid (PT); 7.4% for filamentous
      hemagglutinin; 3.7% for pertactin (PRN); 4.8% for fimbriae types 2 and 3; -0.1%
      for tetanus; -1.9% for diphtheria; 3.7% for poliovirus 1; -0.7% for poliovirus 2
      and 0.3% for poliovirus 3. GMC ratios were 1.97 for PT; 1.56 for filamentous
      hemagglutinin; 1.51 for PRN; 1.33 for fimbriae types 2 and 3; 1.17 for tetanus;
      1.20 for diphtheria; 1.27 for poliovirus 1; 0.90 for poliovirus 2 and 1.34 for
      poliovirus 3. Rates of immediate and unsolicited adverse events, solicited
      injection site reactions and systemic reactions were similar between groups.
      CONCLUSIONS: DTaP5-IPV was safe and immunogenic in children 4-6 years of age.

PMID- 27879554
TI  - Measles and Rubella Seroprevalence Among HIV-infected and Uninfected Zambian
      Youth.
AB  - BACKGROUND: Measles and congenital rubella syndrome remain significant causes of
      morbidity and mortality despite available vaccines. HIV-infected youth may be at
      increased risk of measles because of greater waning immunity after vaccination.
      At a population level, they constitute a potentially large pool of susceptibles
      to measles and rubella. More data among HIV-infected youth in sub-Saharan Africa
      are needed to guide vaccination policy and control strategies. METHODS: This
      cross-sectional study was nested within 2 ongoing studies of malaria and HIV in
      Zambia. Dried blood spot cards from youth (5-15 years) in these studies from 2009
      to 2013 were tested for IgG antibodies to measles and rubella viruses. HIV
      uninfected youth, HIV-infected treatment-naive youth and HIV-infected youth
      receiving antiretroviral therapy (ART) were compared. RESULTS: A total of 617 HIV
      uninfected, 144 HIV-infected treatment-naive and 128 HIV-infected youth receiving
      ART were included in this study. The proportion seropositive for measles virus
      was significantly higher among HIV-uninfected youth (92.5%) compared with HIV
      infected treatment-naive youth (74.1%) and HIV-infected youth receiving ART
      (71.9%). No differences by age were observed. The proportion seropositive for
      rubella virus was significantly higher among HIV-uninfected youth (54.7%)
      compared with HIV-infected treatment-naive youth (41.7%) and HIV-infected youth
      receiving ART (49.6%), with increases observed by age for all groups.
      CONCLUSIONS: Measles seroprevalence was lower among HIV-infected than uninfected
      youth, consistent with waning immunity after measles vaccination. HIV-infected
      youth would benefit from revaccination. Half of all youth in rural Zambia were
      susceptible to rubella and may need targeting for catch-up rubella campaigns when
      measles-rubella vaccine is introduced.

PMID- 27879557
TI  - Chryseobacterium Indologenes-Associated Pneumonia in 2 Neonates.
AB  - Chryseobacterium species are widely distributed in nature and can rarely cause
      human infection. Few cases reported in hospitalized patients are in
      immunocompromised hosts with indwelling devices and associated comorbidities.
      Chryseobacterium species are usually multidrug resistant. We describe 2 cases of
      Chryseobacterium indologenes-associated pneumonia in neonates and review the
      published infant cases.

PMID- 27879556
TI  - Who Gets Severe Gynecomastia Among HIV-infected Children in the United Kingdom
      and Ireland?
AB  - There are few data on gynecomastia in HIV-infected children. Within the
      UK/Ireland's national cohort, 56 of 1873 (3%) HIV-infected children had
      gynecomastia, of which 10 (0.5%) were severe. All 10 had received antiretroviral
      therapy for a median of 27.5 (21, 42) months; 4 of 10 had received efavirenz, 7
      of 10 and 6 of 10 had received stavudine and/or didanosine respectively. Five
      were nonreversible, despite changing antiretroviral therapy, and required breast
      reduction surgery.

PMID- 27879558
TI  - Impact of Pneumococcal Conjugate Vaccines on Selected Head and Neck Infections in
      Hospitalized Israeli Children.
AB  - BACKGROUND: Streptococcus pneumoniae is a major pathogen of pediatric head and
      neck infections (HNIs), for example, acute otitis media (AOM), acute mastoiditis,
      acute bacterial sinusitis and meningitis. The aim of this study was to
      characterize the epidemiology of pneumococcal HNIs (pHNIs) before, during and
      after the introduction of pneumococcal conjugate vaccines (PCVs). METHODS:
      Children 0-16 years of age, who were hospitalized with HNIs in the pediatrics
      department in a general hospital between January 1, 2007, and December 31, 2014,
      were retrospectively identified. Study years were categorized according to the
      PCV introduction timeline: 2007-2008: "pre-PCV years"; 2009-2011: "transition
      years" and 2012-2014: "post-PCV years." pHNIs episodes were defined if
      pneumococcal culture or urine antigen was positive. Children who received >=2
      doses of PCV7/PCV13 were considered as immunized. All other children were
      considered as unimmunized. RESULTS: HNIs accounted for 2.5%-4.7% of the total
      admissions; 3%-17% of them were pHNIs. Eighty-seven pHNI episodes were
      identified: AOM (n = 42), acute mastoiditis (n = 28) and meningitis (n = 17).
      There was a downward trend in the overall incidence of HNIs, and particularly of
      pHNIs, in the post-PCV years. The average age and hospitalization duration of
      children with HNIs/pHNIs remained stable during the study years. In 2009-2010,
      pHNIs incidence sharply decreased, from 7 to 1.74/1000 hospitalized
      children/year, due to ~55% reduction of pneumococcal AOM episodes. An additional
      decrease was observed in the post-PCV years (1.62/1000 hospitalized
      children/year). Immunized children were less likely to present with pHNIs (P =
      0.001) but were more likely to undergo surgery (P = 0.042). CONCLUSION: We
      observed a reduction in pHNIs incidence after PCV program implementation.

PMID- 27879559
TI  - Angiotensin II in Refractory Septic Shock.
AB  - Refractory septic shock is defined as persistently low mean arterial blood
      pressure despite volume resuscitation and titrated vasopressors/inotropes in
      patients with a proven or suspected infection and concomitant organ dysfunction.
      Its management typically requires high doses of catecholamines, which can induce
      significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang
      II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor
      agent that could be used in conjunction with other vasopressors to stabilize
      critically ill patients during refractory septic shock, and reduce catecholamine
      requirements. However, very few clinical data are available to support Ang II
      administration in this setting. Here, we review the current literature on this
      topic to better understand the role of Ang II administration during refractory
      septic shock, differentiating experimental from clinical studies. We also
      consider the potential role of exogenous Ang II administration in specific organ
      dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain
      unresolved and future studies should investigate important topics such as: the
      optimal dose and timing of Ang II administration, a comparison between Ang II and
      the other vasopressors (epinephrine; vasopressin), and Ang II effects on
      microcirculation.

PMID- 27879560
TI  - Temporal Changes in Microrna Expression in Blood Leukocytes from Patients with
      the Acute Respiratory Distress Syndrome.
AB  - BACKGROUND: MicroRNA (miRNA) control gene transcription by binding to and
      repressing the translation of messenger RNA (mRNA). Their role in the acute
      respiratory distress syndrome (ARDS) is undefined. METHODS: Blood leukocytes from
      51 patients enrolled in a prior randomized trial of corticosteroids for ARDS were
      analyzed. After screening eight patients with microarrays for altered miRNA
      expression, 25 miRNAs were selected for further analysis using RT-PCR in all 51
      patients. RESULTS: On day 0, the 51 patients had APACHE III score of 60.4 +/-
      17.7 and PaO2/FiO2 of 117 +/- 49. 21 miRNA were expressed at increased levels in
      blood leukocytes at the onset of ARDS compared with healthy controls. These miRNA
      remained elevated at day 3 and increased further by day 7 (log2 fold change from
      0.66 to 5.7 fold, P <0.05 compared to day 0). In a subgroup analysis (37 patients
      treated with corticosteroids and 14 treated with placebo), the interaction of
      miRNA expression over time and steroid administration was not significant
      suggesting that systemic corticosteroids had no effect on the miRNA detected in
      our study. In contrast, corticosteroids but not placebo decreased IL-6 and C
      reactive protein at day 3 (P < 0.001) demonstrating an early systemic anti
      inflammatory response whereas both treatment arms had decreased values by day 7
      (P <0.001). CONCLUSIONS: Expression of miRNA is increased in blood leukocytes of
      patients with ARDS at day 0 and day 3 and rises further by day 7, when systemic
      inflammation is subsiding. These effects appear independent of the administration
      of steroids, suggesting different inflammatory modifying roles for each in the
      resolving phases of ARDS.

PMID- 27879562
TI  - Effects of Transport Temperature on the Stability of Inflammatory, Hemostasis,
      Endothelial Function, and Oxidative Stress Plasma Biomarker Concentrations.
AB  - BACKGROUND: A number of studies in critically ill patients are conducted outside
      the hospital. Specimens should ideally be transported from out-of-hospital
      setting to a laboratory using dry ice, but this approach is expensive and may not
      be feasible in some circumstances. We, therefore, examined the impact of
      temperature during transport of specimens on the precision of biomarker
      concentrations. OBJECTIVE: To determine the effects of transport temperature
      conditions on biomarker concentrations in specimens processed within 1 h of
      collection. METHODS/PATIENTS: We simulated transport by storing specimens at four
      temperature conditions: packaged at -80 degrees C (control), on dry ice (-79
      degrees C), on cold gel packs (4 degrees C), and at room temperature (RT, 21
      degrees C). We examined eight biomarkers spanning four signaling domains-
      inflammation, hemostasis, endothelial dysfunction, and oxidative stress. We
      calculated mean, median, and percent difference for each biomarker concentration
      compared with the control transport temperature at -80 degrees C in 26 subjects
      (16 hospitalized with severe sepsis and 10 non-hospitalized volunteers). RESULTS:
      Patients with severe sepsis had log-fold higher median concentrations of IL-6, hs
      CRP, D-dimer, E-selectin, sICAM-1, and sVCAM-1 compared with non-hospitalized
      volunteers (P <0.05). When specimens were combined, we observed a <=7% difference
      in the mean and median IL-6, hs-CRP, D-dimer, PAI-1, E-selectin, s-ICAM, s-VCAM,
      and nitrite concentrations for dry ice and cold gel packs transport compared with
      transport at -80 degrees C (P>0.05). Larger differences (up to 12%) were observed
      when biomarker concentrations for PAI-1 and s-VCAM at room temperature were
      compared with transport at -80 degrees C (P >0.05). CONCLUSIONS: Select
      inflammatory, coagulation, endothelial dysfunction, and oxidative stress
      biomarkers can be transported at 4 degrees C on gel packs for 24 h with minimal
      effects on precision.

PMID- 27879561
TI  - Late Therapeutic Intervention with Antibiotics and Fluid Resuscitation Allows for
      a Prolonged Disease Course with High Survival in a Severe Murine Model of Sepsis.
AB  - Current animal models of sepsis often incorporate antibiotics to be consistent
      with clinical standards for treatment of patients in the intensive care unit.
      However, such experimental intervention is commonly initiated very early after
      infectious insult, which likely blunts the progression of systemic inflammation
      and downstream pathology. The objective of this study was to establish an animal
      model of sepsis with delayed therapeutic intervention, allowing a longer disease
      course and downstream pathology, but still resulting in a high survival rate.
      Severe lethal abdominal infection was initiated in young adult (17-18-week-old)
      C57BL/6 mice by cecal slurry (CS) injection. When initiated early (1- or 6-h post
      CS injection), antibiotic treatment (imipenem, 1.5 mg/mouse i.p., twice/day for 5
      days) rescued the majority of mice; however, few of these mice showed evidence of
      bacteremia, cytokinemia, or organ injury. When antibiotic treatment was delayed
      until late time-points (12- or 24-h post-CS injection) the majority of animals
      did not survive beyond 48 h. When fluid resuscitation (physiological saline,
      s.c.) was performed in combination with antibiotic treatment (twice daily)
      beginning at these late time-points, the majority of mice survived (75%) and
      showed bacteremia, cytokinemia, organ dysfunction, and prolonged body weight loss
      (<90% for 4 weeks). We recommend that this new repeated combination treatment
      with antibiotics and fluids resuscitation be initiated at a late time point after
      bacteremia becomes evident because this model more closely mimics the downstream
      pathological characteristics of severe clinical sepsis yet maintains a high
      survival rate. This model would be advantageous for studies on severe sepsis and
      postintensive care illness.

PMID- 27879563
TI  - Pilot Study of Sequence of Segmental Contributions in the Lower Cervical Spine
      During Active Extension and Flexion: Healthy Controls Versus Cervical
      Degenerative Disc Disease Patients.
AB  - STUDY DESIGN: A retrospective study in which, first, a definition of normal
      movement in the cervical spine is formulated. Second, use of this definition in
      differentiating between normal and abnormal movement of the cervical spine is
      evaluated. OBJECTIVE: To formulate a clear definition of the normal sequence of
      segmental contributions in the cervical spine during flexion/extension, and to
      evaluate the sensitivity, specificity, and reliability of sequence of segmental
      contributions analysis in differentiating between normal and abnormal movement of
      the cervical spine in healthy controls and patients with cervical degenerative
      disc disease (CDDD). SUMMARY OF BACKGROUND DATA: To study mobility before and
      after cervical arthroplasty, segmental range of motion (sROM) is most commonly
      used. Analysis of sequence of segmental contributions during flexion and/or
      extension might be more suitable. METHODS: The definition was formulated by
      analyzing flexion cinematographic recordings (FCRs) and extension cinematographic
      recordings (ECRs) in healthy controls. Sequences in ECRs were more consistent
      than in FCRs and were therefore used to define "normal" motion. Five blinded
      spine surgeons scored randomized graphs from ECRs in 20 healthy controls and 10
      preoperative CDDD patients, using this definition, at three time points.
      Sensitivity, specificity, and reliability were calculated. RESULTS: Reliability
      of scoring as normal or abnormal is high (Fleiss kappa of 0.80-0.84, 95%
      confidence interval, CI: 0.66-0.98), sensitivity and specificity are also high,
      with an average sensitivity of 90% (95% CI: 78.4-99.8%), and an average
      specificity of 85% (95% CI: 72.9-96.4%). CONCLUSION: This is the first described
      method that can reliably differentiate between normal or abnormal movement of the
      cervical spine in an individual subject. This enables an observer to determine if
      the normal sequence is restored after arthroplasty. In contrast to the given
      method, sROMs are not able to distinguish between healthy controls and CDDD
      patients. LEVEL OF EVIDENCE: 2.

PMID- 27879565
TI  - Surgical Wound Infection Rates and Risk Factors in Spinal Fusion in a University
      Teaching Hospital in Madrid, Spain.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: To study risk factors linked
      to spinal fusion surgical wound infection (SWI) incidence and compare the
      incidence with rates in Madrid Region, Spain and United States as a whole.
      SUMMARY OF BACKGROUND DATA: SWI is one of the complications posed by spinal
      surgery. Indeed, spinal surgery has a higher infection rate than do other
      orthopedic surgeries such as total hip or knee arthroplasty. The study of risk
      factors that are susceptible to be modified will enable both the incidence of SWI
      and, by extension, related morbidity, mortality, and costs to be reduced.
      METHODS: All patients undergoing spinal fusion at a tertiary hospital from June
      2011 to June 2014 were included. Infection rate was calculated, and the
      association between risk factors and SWI incidence was assessed by reference to
      odds ratio (OR) with univariate and multivariate analysis. RESULTS: The study
      population (n = 892) had a SWI rate of 3.9%. The standardized infection ratio of
      our hospital was 0.58 with respect to the Madrid Region, 0.76 with respect to
      Spain's national rate and 2.05 with respect to the US NHSN/CDC. The multivariate
      analysis showed that predictive factors of SWI were diabetes mellitus (OR 2.81,
      95% confidence interval, CI: 1.18-6.72, P < 0.05), chronic obstructive pulmonary
      disease (COPD) (OR 5.16, 95% CI: 2.04-13.08, P < 0.05), duration of surgery
      higher than the 75th percentile (OR 5.39, 95% CI: 1.77-110.84, P < 0.05) and
      dirty surgery (OR 14.01, 95% CI: 1.01-28.88, P < 0.05). CONCLUSION: Independent
      risk factors for SWI in spinal fusion are existence of diabetes mellitus, COPD,
      duration of surgery higher than the 75th percentile and dirty surgery. Knowing
      these risk factors enables action to be taken to reduce the SWI rate. LEVEL OF
      EVIDENCE: 3.

PMID- 27879564
TI  - Structural Brain Imaging in People With Low Back Pain.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The aim of this study was to
      determine whether low back pain (subacute and chronic) is related to differences
      in brain volume. SUMMARY OF BACKGROUND DATA: Inconsistent findings have been
      reported about the effect of chronic low back pain on brain volume, and the
      effect of subacute low back pain on brain volume has not been sufficiently
      investigated. METHODS: A total of 130 participants were included (23 subacute and
      68 chronic low back pain; 39 healthy controls). The main outcome measure was
      whole and regional brain volume. Clinical outcome measures included pain
      duration, pain intensity, fear avoidance belief questionnaire, Oswestry
      Disability Index, and Beck's Depression Inventory. RESULTS: Decrease in brain
      volume in several regions was observed in chronic low back pain when compared
      with health subjects; however, after correcting for multiple comparisons, no
      significant differences were detected between any of the three groups in whole
      brain volume. Regionally, we detected less gray matter volume in two voxels in
      the middle frontal gyrus in chronic low back pain participants compared with
      healthy controls. None of the clinical outcome measures were correlated with
      brain volume measurements. CONCLUSION: Low back pain (subacute or chronic) is not
      related to significant differences in brain volume after correction for multiple
      comparisons. The effect size was too small to detect possible subtle changes
      unless much larger sample sizes are examined, or it is possible that low back
      pain does not affect brain volume. LEVEL OF EVIDENCE: 5.

PMID- 27879567
TI  - Collar Fixation Is Not Mandatory After Cervical Laminoplasty: A Randomized
      Controlled Trial.
AB  - STUDY DESIGN: Prospective randomized controlled study. OBJECTIVES: To determine
      the effect of collar-aided fixation on outcomes after laminoplasty for cervical
      compressive myelopathy. SUMMARY OF BACKGROUND DATA: Patients are often placed in
      a Philadelphia collar for weeks after cervical laminoplasty. However, the benefit
      of postoperative collar use remains controversial. We hypothesized that treatment
      outcomes in postoperative pain in patients without collars would not be inferior
      to the outcomes in patients using Philadelphia collars for 2 weeks. METHODS: This
      trial analyzed 74 patients (52 males, 22 females, mean age 72.7 years) with
      cervical compressive myelopathy who had undergone double-door laminoplasty.
      Before surgery, we randomly assigned patients to the collar-fixation (CF) group
      (postoperative Philadelphia collar for 2 weeks) or the no-collar (NC) group. The
      primary outcome was the visual analog scale (VAS) for cervical pain up to 1 year
      after surgery. Secondary outcomes were Japanese Orthopedics Association score,
      Short Form 36 score (SF-36), cervical range of motion (ROM), lordotic angle, and
      complications. RESULTS: VAS scores up to 1 year after operation were similar with
      or without collar fixation (P = 0.487, two-way ANOVA). JOA scores improved
      significantly in both groups (P = 0.002 in CF, P < 0.001 in NC). There was no
      statistically significant difference between groups with regard to the
      improvement of JOA scores (54.9% in CF, 47.0% in NC, P = 0.80). The improvement
      in SF-36 was similar in both groups. Loss of ROM and lordotic angle of the
      cervical spine did not differ between groups (P = 0.61 in CF, P = 0.82 in NC).
      The incidence of complications was similar in both groups. CONCLUSION: The VAS
      scores of cervical pain with the postoperative treatment without collar fixation
      were not inferior to those when using Philadelphia collars for 2 weeks. Moreover,
      other outcomes such as JOA scores, SF-36, ROM, lordotic angle, and complications
      were similar in both groups. LEVEL OF EVIDENCE: 2.

PMID- 27879566
TI  - Effect of an Acid-sensing Ion Channels Inhibitor on Pain-related Behavior by
      Nucleus Pulposus Applied on the Nerve Root in Rats.
AB  - STUDY DESIGN: Controlled, interventional animal study. OBJECTIVE: To examine the
      effect of an inhibitor of acid-sensing ion channel 3 (ASIC3) on pain-related
      behavior induced by application of the nucleus pulposus (NP) onto the dorsal root
      ganglion (DRG) in rats. SUMMARY OF BACKGROUND DATA: ASIC3 is associated with
      acidosis pain in inflamed or ischemic tissues and is expressed in sensory neurons
      and NP cells. The ASIC3 inhibitor, APETx2, increases the mechanical threshold of
      pain in models of knee osteoarthritis or postoperative pain. However, the
      efficacy of APETx2 for pain relief in the NP application model remains unknown.
      METHODS: Autologous NP was applied to the left L5 nerve root of 183 adult female
      Sprague-Dawley rats. The DRGs were treated with NP plus one of the following four
      treatments: saline solution (SM), low (0.01 MUg: LD), medium (0.1 MUg: MD), or
      high dose (1.0 MUg: HD) of APETx2. Behavioral testing was performed to
      investigate the mechanical withdrawal threshold using von Frey hairs. Expression
      of nerve growth factor, hypoxia-inducible factor-1alpha (HIF1alpha), activating
      transcription factor-3, and ionized calcium-binding adaptor molecule-1 was
      evaluated using immunohistochemistry. Statistical differences among multiple
      groups were assessed using the Steel test, the Tukey-Kramer test, and the Dunnett
      test. P < 0.05 were considered significant. RESULTS: The thresholds in the HD
      group were higher than those in the SM group at Days 14 and 21 (P < 0.05). In the
      MD group, the threshold was higher than in the SM group at Day 14 (P < 0.05).
      High doses of APETx2 reduced the expression of HIF1alpha after Day 14 compared
      with the SM group (P < 0.05). CONCLUSION: APETx2 significantly improved pain
      related behavior in a dose-dependent manner. APETx2 may inhibit ASIC3 and partly
      inhibit Nav1.8 channels. This ASIC3 channel inhibitor may be a potential
      therapeutic agent in early-stage lumbar disc herniation. LEVEL OF EVIDENCE: N/A.

PMID- 27879568
TI  - Effect of Immunotherapy Status on Outcomes in Patients With Metastatic Melanoma
      to the Spine.
AB  - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: We performed a
      retrospective study of patients treated at our institution over the last 3 years
      to assess predictive value of immunotherapy exposure on overall survival (OS) of
      patients with metastatic melanoma to the spine in an effort to better inform
      surgical decision making. SUMMARY OF BACKGROUND DATA: Modern management of
      metastatic melanoma includes adjuvant targeted therapies and immunomodulators
      that have shown to significantly improve OS. METHODS: Baseline characteristics
      were recorded for patients, including performance scores, use of adjuvant
      therapies, progression-free survival (PFS), and OS. Pre-procedural imaging was
      reviewed to assign Spinal Instability Neoplastic Score (SINS) and epidural spinal
      cord compression (ESCC) classification. Kaplan-Meier survival analysis was
      performed. RESULTS: We identified 18 patients with metastatic melanoma to the
      spine treated between 2012 and 2015. Instrumented fixation was performed for
      median SINS 12. Eleven patients undergoing surgery were noted to have ESCC
      classification of at least 2. Median OS for the entire group was 117 days.
      Univariate analysis revealed that prior immunotherapy treatment was associated
      with significantly shorter survival following surgery (median survival 98 vs. 315
      days for patients previously on immunotherapies compared to those who were not).
      Meanwhile, neither BRAF mutation status nor treatments targeting these pathways
      were associated with this prognostic effect. CONCLUSION: Progressive metastatic
      spine disease following immunotherapy may herald a particularly aggressive time
      point and recognizing this natural history is critical for appropriate multimodal
      planning. LEVEL OF EVIDENCE: 4.

PMID- 27879570
TI  - Bone Turnover Markers as a New Predicting Factor for Nonunion After Spinal Fusion
      Surgery.
AB  - STUDY DESIGN: Retrospective observational study. OBJECTIVE: We investigated
      whether bone turnover markers could be a useful indicator for prediction of
      nonunion. SUMMARY OF BACKGROUND DATA: Nonunion is a major complication of lumbar
      spinal fusion surgery. The involvement of bone turnover in the process of bony
      union in spinal fusion surgery is, however, poorly understood. METHODS: Of the 74
      patients analyzed, 13 were diagnosed with nonunion. We evaluated the significance
      of the following risk factors: age, sex, number of fused segments, serum levels
      of total alkaline phosphatase, procollagen type 1 amino-terminal propeptide
      (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and albumin, and
      history of diabetes mellitus, cigarette smoking, or alcohol use. We also defined
      the bone turnover ratio (BTR) as a value that equals serum TRACP-5b concentration
      divided by serum P1NP concentration to evaluate patients' individual bone
      turnover balance and investigated the significance of BTR as a risk factor.
      RESULTS: Univariate analysis showed that older age, malnutrition, and lower P1NP
      are risk factors for nonunion. Stepwise logistic regression analysis revealed
      that in the presence of lower P1NP, higher TRACP-5b becomes a risk factor.
      Furthermore, we identified BTR as the most significant risk factor for nonunion.
      The optimum cut-off value of BTR by receiver-operating characteristic curve was
      11.74. CONCLUSION: These findings show a relation between bone turnover and
      nonunion after spinal fusion surgery. The measurement of bone turnover markers
      could potentially be used to predict nonunion after spinal fusion surgery. LEVEL
      OF EVIDENCE: 4.

PMID- 27879571
TI  - Radiographic Predictors for Mechanical Failure After Adult Spinal Deformity
      Surgery: A Retrospective Cohort Study in 138 Patients.
AB  - STUDY DESIGN: Retrospective cohort study at a single institution. OBJECTIVE: We
      aimed at estimating the rate of revision procedures and identify radiographic
      predictors of mechanical failure after adult spinal deformity surgery. SUMMARY OF
      BACKGROUND DATA: Mechanical failure rates after adult spinal deformity surgery
      range 12% to 37% in literature. Although the importance of spinal and spino
      pelvic alignment is well documented for surgical outcome and ideal alignment has
      been proposed as sagittal vertical axis (SVA) < 5 cm, pelvic tilt < 20 degrees 
      and lumbar lordosis (LL) = pelvic incidence +/- 9 degrees , the role of
      radiographic sagittal spine parameters and alignment targets as predictors for
      mechanical failure remains uncertain. METHODS: A consecutive cohort of adult
      spinal deformity patients who underwent corrective surgery with at least 5 levels
      of instrumentation between January 2008 and December 2012 at a single tertiary
      spine unit were followed for at least 2 years. Time to death or failure was
      recorded and cause-specific Cox regressions were applied to evaluate predictors
      for mechanical failure or death. RESULTS: A total of 138 patients with median age
      of 61 years were included for analysis. Follow up ranged 2.1 to 6.8 years. In
      total 47% had revision and estimated failure rates were 16% at 1 year increasing
      to 56% at 5 years. A multivariate analysis adjusting for age at surgery showed
      increased hazard of failure from LL change > 30 degrees , postoperative TK > 50
      degrees , and SS <=30 degrees . LL change was mostly because of 3-column
      osteotomy and ending the instrumentation at L5 or S1 increased the hazard of
      failure more than 6 fold compared with more cranial lumbar levels. CONCLUSION:
      Mechanical failure rate was 47% after adult spinal deformity corrective surgery.
      LL change > 30 degrees , postoperative TK > 50 degrees , and postoperative SS
      <=30 degrees  were independent radiographic predictors associated with increased
      hazard of failure. LEVEL OF EVIDENCE: 4.

PMID- 27879572
TI  - Importance of Distal Fusion Level in Major Thoracolumbar and Lumbar Adolescent
      Idiopathic Scoliosis Treated by Rod Derotation and Direct Vertebral Rotation
      Following Pedicle Screw Instrumentation.
AB  - STUDY DESIGN: A retrospective comparative study. OBJECTIVE: The aim of this study
      was to analyze the exact distal fusion level in the treatment of major
      thoracolumbar and lumbar (TL/L) adolescent idiopathic scoliosis (AIS) using rod
      derotation (RD) and direct vertebral rotation (DVR) following pedicle screw
      instrumentation (PSI). SUMMARY OF BACKGROUND DATA: Proper determination of distal
      fusion level is a very important factor in deformity correction and preservation
      of motion segments in the treatment of major TL/L AIS. METHODS: AIS patients with
      major TL/L curves (n = 64) treated by PSI with RD and DVR methods with a minimum
      2-year follow-up were divided into AL3 (flexible) and BL3 (rigid) according to
      the flexibility and rotation by preoperative bending radiographs. RESULTS: There
      was no significant difference in TL/L (major) curve between the AL3 and BL3
      groups postoperatively (P = 0.933) and at the last follow-up (P = 0.144). In
      addition, there was no significant difference in thoracic (minor) and
      compensatory (caudal) curve postoperatively (thoracic curve: P = 0.828,
      compensatory curve: P = 0.976); however, there was a significant difference in
      compensatory (caudal) curve at the last follow-up (P = 0.041). The overall
      prevalence of unsatisfactory results was 28.1% (18/64 patients), and the
      prevalence was 15.2% (7/46) in the AL3 group and 61.1% (11/18) in the BL3 group,
      which was significantly different (P < 0.05). CONCLUSION: Lowest instrumented
      vertebra (LIV) would be selected at L3 (EV) when the curve is flexible; L3
      crosses CSVL with a rotation of less than grade II in preoperative bending
      radiographs. However, if the curve is rigid, LIV should be extended to L4 (EV +
      1) in order to prevent the adding-on phenomenon in the treatment of major TL/L
      AIS using RD and DVR following PSI. LEVEL OF EVIDENCE: 4.

PMID- 27879573
TI  - Multimodal Analgesia Versus Intravenous Patient-Controlled Analgesia for
      Minimally Invasive Transforaminal Lumbar Interbody Fusion Procedures.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To compare postoperative
      narcotic consumption and pain scores between multimodal analgesia (MMA) and
      patient-controlled analgesia (PCA) following minimally invasive transforaminal
      lumbar interbody fusion (MIS TLIF). SUMMARY OF BACKGROUND DATA: A multimodal
      analgesic approach to pain management may lead to decreased pain and narcotic
      consumption after orthopedic procedures. Additional evidence is, however,
      required to determine how MMA compares to intravenous PCA after MIS TLIF.
      METHODS: Patients undergoing 1-level MIS TLIF followed by either MMA or PCA at
      our institution were compared in terms of inpatient pain scores, narcotic
      consumption, hospital length of stay, rates of surgical complications, rates of
      inpatient nausea/vomiting, rates of postoperative urinary retention, and rates of
      narcotic consumption during the months after discharge. RESULTS: A total of 139
      patients met inclusion criteria. Of these, 39 (28.1%) received MMA and 100
      (71.9%) received PCA. Demographic and comorbidity characteristics did not differ
      between cohorts. Compared with patients receiving PCA, patients receiving MMA had
      a lower rate of inpatient narcotic consumption (2.8 +/- 1.9 vs. 5.3 +/- 4.4 oral
      morphine equivalents/hour, P < 0.001), a lower rate of inpatient nausea/vomiting
      (20.5% vs. 48.0%; P = 0.003), and a shorter hospital length of stay (53.0 +/-
      25.3 vs. 62.6 +/- 24.4 h, P = 0.041). There were no differences in Numeric Rating
      Scale pain score between cohorts for day 0, postoperative day 1, or postoperative
      day 2 (P > 0.05 for each). There was no difference in the rate of postoperative
      urinary retention (P > 0.05). Similarly, there were no differences in narcotic
      consumption at 6 or 12 weeks postoperatively (P > 0.05 for each). CONCLUSION:
      These findings suggest that MMA results in reduced inpatient hospital narcotic
      consumption compared with PCA after MIS TLIF. The decrease in narcotic
      consumption may contribute to the observed decrease in the rate of inpatient
      nausea/vomiting and shorter hospital length of stay. Importantly, MMA and PCA
      resulted in similar analgesia for patients during the inpatient stay. LEVEL OF
      EVIDENCE: 4.

PMID- 27879574
TI  - Seasonal Variations in the Risk of Reoperation for Surgical Site Infection
      Following Elective Spinal Fusion Surgery: A Retrospective Study Using the
      Japanese Diagnosis Procedure Combination Database.
AB  - STUDY DESIGN: A retrospective study of data abstracted from the Diagnosis
      Procedure Combination (DPC) database, a national representative database in
      Japan. OBJECTIVE: The aim of this study was to examine seasonal variations in the
      risk of reoperation for surgical site infection (SSI) following spinal fusion
      surgery. SUMMARY OF BACKGROUND DATA: Although higher rates of infection in the
      summer than in other seasons were thought to be caused by increasing inexperience
      of new staff, high temperature, and high humidity, no studies have examined
      seasonal variations in the risk of SSI following spinal fusion surgery in the
      country where medical staff rotation timing is not in summer season. In Japan,
      medical staff rotation starts in April. METHODS: We retrospectively extracted the
      data of patients who were admitted between July 2010 and March 2013 from the DPC
      database. Patients were included if they were aged 20 years or older and
      underwent elective spinal fusion surgery. The primary outcome was reoperation for
      SSI during hospitalization. We performed multivariate analysis to clarify the
      risk factors of primary outcome with adjustment for patient background
      characteristics. RESULTS: We identified 47,252 eligible patients (23,659 male,
      23,593 female). The mean age of the patients was 65.4 years (range, 20-101 yrs).
      Overall, reoperation for SSI occurred in 0.93% of the patients during
      hospitalization. The risk of reoperation for SSI was significantly higher in
      April (vs. February; odds ratio, 1.93; 95% confidence interval, 1.09-3.43, P =
      0.03) as well as other known risk factors. In subgroup analysis with
      stratification for type of hospital, month of surgery was identified as an
      independent risk factor of reoperation for SSI among cases in an academic
      hospital, although there was no seasonal variation among those in a nonacademic
      hospital. CONCLUSION: This study showed that month of surgery is a risk factor of
      reoperation for SSI following elective spinal fusion surgery, nevertheless, in
      the country where medical staff rotation timing is not in summer season. LEVEL OF
      EVIDENCE: 3.

PMID- 27879575
TI  - Cost-Utility Analysis of Pedicle Screw Removal After Successful Posterior
      Instrumented Fusion in Thoracolumbar Burst Fractures.
AB  - STUDY DESIGN: A cost-utility analysis (CUA). OBJECTIVE: The aim of this study was
      to determine the cost-effectiveness of pedicle screw removal after posterior
      fusion in thoracolumbar burst fractures. SUMMARY OF BACKGROUND DATA: Pedicle
      screw instrumentation is a standard fixation method for unstable thoracolumbar
      burst fracture. However, removal of the pedicle screw after successful fusion
      remains controversial because the clinical benefits remain unclear. CUA can help
      clinicians make appropriate decisions about optimal health care for pedicle screw
      removal after successful fusion in thoracolumbar burst fractures. METHODS: We
      conducted a single-center, retrospective, longitudinal matched-cohort study of
      prospectively collected outcomes. In total, 88 consecutive patients who had
      undergone pedicle screw instrumentation for thoracolumbar burst fracture with
      successful fusion confirmed by computed tomography (CT) were used in this study.
      In total, 45 patients wanted to undergo implant removal surgery (R group), and 43
      decided not to remove the implant (NR group). A CUA was conducted from the health
      care perspective. The direct costs of health care were obtained from the medical
      bill of each patient. Changes in health-related quality of life (HRQoL) scores,
      validated by Short Form 6D, were used to calculate quality-adjusted life-years
      (QALYs). Total costs and gained QALY were calculated at 1 year (1 year) and 2
      years (2 years) compared with baseline. Results are expressed as an incremental
      cost-effectiveness ratio (ICER). Different discount rates (0%, 3%, and 5%) were
      applied to both cost and QALY for sensitivity analysis. RESULTS: Baseline patient
      variables were similar between the two groups (all P > 0.05). The additional
      benefits of implant removal (0.201 QALY at 2 years) were achieved with additional
      costs ($2541 at 2 years), equating to an ICER of $12,641/QALY. On the basis of
      the different discount rates, the robustness of our study's results was also
      determined. CONCLUSION: Implant removal after successful fusion in a
      thoracolumbar burst fracture is cost-effective until postoperative year 2. LEVEL
      OF EVIDENCE: 3.

PMID- 27879576
TI  - Analysis of Sagittal Parameters in Patients Undergoing One- or Two-Level Closing
      Wedge Osteotomy for Correcting Thoracolumbar Kyphosis Secondary to Ankylosing
      Spondylitis.
AB  - STUDY DESIGN: Retrospective analysis of clinical records. OBJECTIVE: To assess
      and compare the improvement in sagittal balance after one- or two-level closing
      wedge osteotomy for correcting thoracolumbar kyphosis secondary to ankylosing
      spondylitis (AS). SUMMARY OF BACKGROUND DATA: Closing wedge osteotomy represents
      a common approach to correct kyphosis in AS. Although several reports have
      described the outcomes of one- or two-level closing wedge osteotomy in terms of
      sagittal parameters, data comparing the outcomes of these procedures are scarce.
      METHODS: Between January 2010 and December 2014, 22 patients with AS underwent
      closing wedge osteotomy (one-level, 12 patients; two-level, 10 patients) for
      correcting thoracolumbar kyphosis (mean follow-up, 24.8 months; range, 12-60
      months). Preoperative and postoperative chin-brow vertical angle, and the
      sagittal parameters of the vertebral osteotomy segment were documented and
      compared. Perioperative and postoperative complications were also recorded.
      RESULTS: The chin-brow vertical angle improved significantly, from 55.0 degrees 
      +/- 27.3 degrees  to 4.7 degrees  +/- 4.9 degrees  and from 38.2 degrees  +/-
      14.9 degrees  to 3.2 degrees  +/- 5.4 degrees  in the one-level and two-level
      groups, respectively. The total correction (thoracic kyphosis and lumbar
      lordosis) was 32.8 degrees  +/- 18.2 degrees  and 53.7 degrees  +/- 9.4 degrees 
      in the one-level and two-level groups, respectively. No death, complete
      paralysis, or vascular complications occurred during the procedure, but
      cerebrospinal fluid leak was noted in one and two patients from the one-level and
      two-level groups, respectively. A distal pedicle screw adjacent to the osteotomy
      segment became loose during surgery in one patient (one-level group).
      Postoperatively, no transient neurological deficit, infection, delay union, or
      loosening or breaking of the internal fixation devices was observed. Osteotomy
      site fusion was achieved in all patients, and the Oswestry Disability Index
      scores improved significantly. CONCLUSION: Closing wedge osteotomy is effective
      and safe for correcting thoracolumbar kyphosis in patients with AS. Significant
      correction and improvement in all sagittal parameters were noted in both groups,
      but two-level closing wedge osteotomy provided better correction. LEVEL OF
      EVIDENCE: 3.

PMID- 27879577
TI  - Potential Involvement of the IL-6/JAK/STAT3 Pathway in the Pathogenesis of
      Intervertebral Disc Degeneration.
AB  - STUDY DESIGN: Laboratory study. OBJECTIVE: To elucidate the potential involvement
      of the interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducers and activator
      of transcription (STAT3) pathway in the development of intervertebral disc (IVD)
      degeneration. SUMMARY OF BACKGROUND DATA: IL-6 plays a crucial role in IVD
      degeneration; however, the downstream intracellular signaling of IL-6 in the IVD
      is not fully understood. METHODS: The expression levels of IL-6 and suppressors
      of cytokine signaling 3 (SOCS3), a target gene of the IL-6/JAK/STAT3 pathway,
      were evaluated in rat and human degenerated IVD samples. The effects of IL-6 on
      primary rat annulus fibrosus (AF) cells were analyzed using quantitative PCR,
      immunocytochemistry, and Western blotting. The potential efficacy of a JAK
      inhibitor, CP690,550, in neutralizing the effect of IL-6 was evaluated in vitro.
      RESULTS: A high expression of IL-6 and SOCS3 was observed in both rat and human
      degenerated IVD samples. In rat AF cells, IL-6 markedly induced the
      phosphorylation of STAT3 and the expression of cyclooxygenase-2 and matrix
      metalloprotease-13. CP690,550 significantly suppressed the phosphorylation of
      STAT3 and offset the catabolic effect of IL-6 in rat AF cells. CONCLUSION: Our
      results suggest that the IL-6/JAK/STAT3 pathway is involved in the pathogenesis
      of IVD degeneration and that CP690,550 suppresses the catabolic effect of the IL
      6 in the IVD. LEVEL OF EVIDENCE: N/A.

PMID- 27879578
TI  - Retrospective Analysis of Congenital Scoliosis: Associated Anomalies and Genetic
      Diagnoses.
AB  - STUDY DESIGN: Retrospective study of a series of 286 patients with congenital
      scoliosis (CS). OBJECTIVE: To describe a large cohort of patients with CS and to
      propose an algorithm for genetic investigations SUMMARY OF BACKGROUND DATA.: CS
      is characterized by a spine curvature due to congenital malformations of the
      vertebrae and is frequently associated to other anomalies. The underlying causes
      remain unclear in most patients, although we know that genetics plays a role in
      the development of vertebral defects. METHODS: Institutional review board
      approval was obtained. We performed a retrospective study by consulting the
      hospital charts of 286 patients with CS seen at the CHU Sainte-Justine, Montreal,
      from 2004 to 2015. We compile information on radiological findings, associated
      malformations, and genetic tests. RESULTS: Results showed that 67.1% of patients
      had associated anomalies affecting different systems. Only a minority of patients
      had a syndromic diagnosis to explain their CS. Nevertheless, array comparative
      genomic hybridization performed in a minority of patients showed a high detection
      rate (31.3% had a chromosomal anomaly among 32 tested). CONCLUSION: We suggest
      that every patient with CS should have thorough investigations to rule out
      associated anomalies and that different genetic tests should be offered according
      to the associated clinical findings. LEVEL OF EVIDENCE: 4.

PMID- 27879579
TI  - Discussion: Do Prolonged Prophylactic Antibiotics Reduce the Incidence of
      Surgical-Site Infections in Immediate Prosthetic Breast Reconstruction?

PMID- 27879580
TI  - Cohort Study to Assess the Impact of Breast Implants on Breastfeeding.
AB  - BACKGROUND: The objective of this study was to evaluate the impact of breast
      implant surgery and its approaches on lactation by comparing women with and
      without breast implants at the time of childbirth. METHODS: Between April of 2013
      and July of 2014, in Rosario (Sanatorio de la Mujer and Centro Quirurgico
      Rosario), Argentina, a prospective cohort study of women with and without breast
      implants was performed. Of a total of 3950 births that occurred during this
      period, 200 patients with similar anthropometric characteristics (maternal and
      newborn) were selected. Breastfeeding (exclusive or mixed) was compared with
      artificial feeding at 24 and 48 hours and 30 days in both groups, and the type of
      incision was also compared. RESULTS: Breastfeeding at 30 days showed a
      nonsignificant trend favoring the control group (OR, 7.39; 95 percent CI, 0.92 to
      339.2). The percentage of women with implants who succeeded in establishing
      breastfeeding (exclusive or mixed) was very high (93 percent). In the control
      group, 99 percent of the women were breastfeeding at 30 days. In a comparison of
      the submammary and areola incision, breastfeeding showed odds ratios of 0.78 (95
      percent CI, 0.33 to 1.87) at 24 hours, 1.10 (95 percent CI, 0.48 to 2.56) at 48
      hours, and 0.18 (95 percent CI, 0.36 to 1.82) at 30 days. CONCLUSIONS: This study
      shows that most patients with breast implants were able to establish
      breastfeeding. However, there is a higher number of women without implants that
      established exclusive breastfeeding. No significant difference was found between
      the different surgical approaches. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 27879581
TI  - Matching Procedures at the Time of Immediate Breast Reconstruction: An American
      College of Surgeons National Surgical Quality Improvement Program Study of 24,191
      Patients.
AB  - BACKGROUND: The purpose of this study was to assess for compounded risk of
      postoperative morbidity with the addition of a simultaneous contralateral breast
      matching procedure at the time of mastectomy and immediate breast reconstruction.
      METHODS: 2005 to 2012 American College of Surgeons National Surgical Quality
      Improvement Program databases were used to identify cases of mastectomy and
      immediate breast reconstruction with and without simultaneous contralateral
      breast matching procedures. Matching procedures included mastopexy, reduction
      mammaplasty, and augmentation mammaplasty. Thirty-day postoperative morbidity was
      assessed using univariable and multivariable logistic regression. RESULTS: Of
      59,766 mastectomy patients, 24,191 (40 percent) underwent immediate breast
      reconstruction: 903 (3.7 percent) underwent matching procedures and 23,288 (96.3
      percent) did not. Univariable logistic regression demonstrated that the matching
      procedure group had statistically significantly higher overall morbidity (OR,
      1.288; 95 percent CI, 1.022 to 1.623; p = 0.032). Although surgical and systemic
      morbidity did not differ significantly, the matching procedure group demonstrated
      higher risk for superficial surgical-site infection (OR, 1.57; 95 percent CI,
      1.066 to 2.31; p = 0.022), reconstruction failure (OR, 1.69; 95 percent CI, 1.014
      to 2.814; p = 0.044), and pulmonary embolism (OR, 2.54; 95 percent CI, 1.01 to
      6.37; p = 0.048). Controlling for possible confounders, multivariable logistic
      regression rendered the relationship between matching procedure and complications
      insignificant (OR, 1.17; 95 percent CI, 0.92 to 1.48; p = 0.2). CONCLUSION: These
      data suggest that preoperative comorbidities and other patient-related factors
      may have a larger influence on postoperative morbidity than the addition of a
      contralateral matching procedure alone. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 27879582
TI  - Carbon Dioxide-Based versus Saline Tissue Expansion for Breast Reconstruction:
      Results of the XPAND Prospective, Randomized Clinical Trial.
AB  - BACKGROUND: AeroForm is a new type of remote-controlled, needle-free, carbon
      dioxide-based expander involving a potentially faster method of tissue expansion.
      Results are presented here from the AirXpanders Patient Activated Controlled
      Tissue Expander pivotal trial comparing AeroForm to saline tissue expanders.
      METHODS: Women undergoing two-stage breast reconstruction were randomized at 17
      U.S. sites in this U.S. Food and Drug Administration-approved investigational
      device exemption trial. Expansion in the investigational arm was performed by the
      patient in 10-cc increments up to 30 cc/day of carbon dioxide and in the control
      arm by the physician with periodic bolus injections of saline. Safety endpoints,
      expansion and reconstruction times, pain, and satisfaction were assessed.
      RESULTS: One hundred fifty women were treated: 98 with carbon dioxide expanders
      (n = 168) and 52 with saline expanders (n = 88). The treatment success rate (all
      breasts exchanged successfully excluding non-device-related failures) was 96.1
      percent for carbon dioxide and 98.8 percent for saline. Median time to full
      expansion and completion of the second-stage operation was 21.0 and 108.5 days
      (carbon dioxide) versus 46.0 and 136.5 days (saline), respectively, with a
      similar rate of overall complications. Ease of use for the carbon dioxide
      expander was rated high by patients (98 percent) and physicians (90 percent).
      CONCLUSIONS: The AirXpanders Patient Activated Controlled Tissue Expander trial
      results demonstrate that a carbon dioxide-based expander is an effective method
      of tissue expansion with a similar overall adverse event rate compared to saline
      expanders, and provides a more convenient and expedient expansion. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

PMID- 27879583
TI  - Breast Tissue Expanders with Magnetic Ports: Clinical Experience at 1.5 T.
AB  - BACKGROUND: The purpose of this study was to evaluate breast tissue expanders
      with magnetic ports for safety in patients undergoing abdominal/pelvic magnetic
      resonance angiography before autologous breast reconstruction. METHODS: Magnetic
      resonance angiography of the abdomen and pelvis at 1.5 T was performed in 71
      patients in prone position with tissue expanders with magnetic ports labeled "MR
      Unsafe" from July of 2012 to May of 2014. Patients were monitored during magnetic
      resonance angiography for tissue expander-related symptoms, and the chest wall
      tissue adjacent to the tissue expander was examined for injury at the time of
      tissue expander removal for breast reconstruction. Retrospective review of these
      patients' clinical records was performed. T2-weighted fast spin echo, steady
      state free precession and gadolinium-enhanced spoiled gradient echo sequences
      were assessed for image artifacts. RESULTS: No patient had tissue expander or
      magnetic port migration during the magnetic resonance examination and none
      reported pain during scanning. On tissue expander removal (71 patients, 112
      implants), the surgeons reported no evidence of tissue damage, and there were no
      operative complications at those sites of breast reconstruction. CONCLUSION:
      Magnetic resonance angiography of the abdomen and pelvis in patients with certain
      breast tissue expanders containing magnetic ports can be performed safely at 1.5
      T for pre-autologous flap breast reconstruction perforator vessel mapping.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 27879584
TI  - Stacked Thoracodorsal Artery Perforator Flaps for Unilateral Breast
      Reconstruction.
AB  - The thoracodorsal artery perforator flap is reliable and safe for breast
      reconstruction, but stacking bilateral thoracodorsal artery perforator flaps for
      unilateral reconstruction to achieve greater volumes has not been reported. To
      create a stacked thoracodorsal artery perforator flap, the ipsilateral flap is
      transferred as an island, and the contralateral flap is transferred as a
      microvascular free flap. In this article, the authors present their 8-year 14-
      patient experience with stacked thoracodorsal artery perforator flaps for
      unilateral breast reconstruction. Patients' ages ranged from 33 to 72 years
      (mean, 52.6 years). Mean follow-up time was 48.1 months (range, 1 to 98 months).
      Flaps measured between 22 * 6 cm and 32 * 8 cm and weighed between 110 and 550 g.
      Two of the island flaps had steatofibrosis of the distal 3 cm, which was resected
      and closed directly. The rest of the island flaps and all 14 free flaps healed
      uneventfully. At the time of follow-up, all flaps appeared healthy, and the
      reconstructed breast had a similar appearance and volume as the contralateral
      side. The donor areas had almost no functional deficit, and the final scar was
      aesthetically acceptable, especially when the ascending oblique design was used.
      This represents the first description of stacked thoracodorsal artery perforator
      flaps for unilateral breast reconstruction. This novel addition to the
      reconstructive surgeon's selection of methods is a safe and reliable option for
      large-volume unilateral breast reconstruction. It allows for symmetry without
      requiring prostheses or reduction of the contralateral side.

PMID- 27879585
TI  - Postoperative Edema Resolution following Rhinoplasty: A Three-Dimensional
      Morphometric Assessment.
AB  - BACKGROUND: The final result of rhinoplasty may be masked for several months
      after surgery because of postoperative edema; however, no objective evidence
      supports this time estimate. The purpose of this study was to three-dimensionally
      quantify the decrease in postsurgical nasal edema following rhinoplasty over the
      first postoperative year. METHODS: This was a retrospective, three-dimensional,
      morphometric study of primary, open rhinoplasty patients. Subjects with at least
      three postoperative three-dimensional images up to 1 year were included. Patients
      were excluded for closed or secondary procedures or cleft deformities. Images
      were assessed using three-dimensional stereophotogrammetry (Vectra) and
      volumetric analysis (Geomagic). Baseline nasal volume (time 0) occurred at the
      first postoperative visit at 1 to 2 weeks. All subsequent nasal volume
      measurements were calculated as a percentage of baseline values. Data points from
      all patients were pooled, and a six-point moving average was used to create an
      inverse function line of best fit. RESULTS: Forty patients were included, with
      146 three-dimensional photographs quantified. The equation for the inverse
      function line of best fit of the six-point moving average was y = 1.484 (1/x) +
      0.844 (R = 0.85, p < 0.01). According to this equation, approximately two-thirds
      of edema resolves within the first month, 95 percent after 6 months, and 97.5
      percent after 1 year. A plateau is reached at 84.4 percent of the original
      postoperative volume. CONCLUSIONS: This study provides quantitative evidence to
      predict decrement of rhinoplasty edema with time. Three-dimensional morphometric
      assessment demonstrated a two-thirds decrease in edema at 1 month, a 95 percent
      decrease at 6 months, and a 97.5 percent decrease at 1 year. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 27879586
TI  - Separation, Aspiration, and Fat Equalization: SAFE Liposuction Concepts for
      Comprehensive Body Contouring.
AB  - BACKGROUND: Separation, aspiration, and fatty equilibration (SAFE) liposuction
      uses a process approach to body contouring and minimizes injury to surrounding
      structures. The multistep process allows for (1) fat separation, (2)
      lipoaspiration, and (3) fat equalization. The purpose of this study was to review
      both outcomes and complications of primary SAFE liposuction. METHODS:
      Retrospective chart review was completed of patients undergoing SAFE liposuction
      from January of 2006 to January of 2011. Patient selection was limited to those
      undergoing liposuction alone with no adjuvant excisional procedures. Data were
      collected regarding demographics, body mass index, operative details, and
      outcomes. RESULTS: Seven hundred thirty-four patients were identified as having
      undergone SAFE liposuction. One hundred twenty-nine patients were found to have
      been treated with liposuction alone. Patient age ranged from 18 to 42 years and
      body mass index ranged from 18 to 42 kg/m (mean, 26.3 kg/m). Seven patients (5.4
      percent) underwent treatment of the face and neck, six patients (4.7 percent)
      underwent treatment of upper extremities, 13 patients (10.1 percent) underwent
      treatment of the chest, 20 patients (15.5 percent) underwent treatment of lower
      extremities, 32 patients (24.8 percent) underwent treatment of the
      circumferential trunk, and 51 patients (39.5 percent) underwent treatment of
      circumferential trunk and additional area(s). No major complications occurred.
      Five of the 129 patients (3.87 percent) developed the minor complication of
      seroma formation. CONCLUSIONS: SAFE liposuction is a multistep process approach
      to body contouring consisting of (1) fat separation, (2) lipoaspiration, and (3)
      fat equalization. The results of this study show such technique to be safe and
      effective. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 27879587
TI  - Psychological Outcomes of Labiaplasty: A Prospective Study.
AB  - BACKGROUND: Although the demand for labiaplasty has increased rapidly over the
      past decade, little is known about the psychological outcomes of this procedure.
      In particular, there is a lack of prospective controlled studies to assess the
      effects of labiaplasty on women's psychological well-being and intimate
      relationship quality. Nor has research investigated whether preoperative patient
      characteristics predict satisfaction with surgery. METHODS: The current study
      used a prospective controlled design. Participants were 29 adult Australian women
      who underwent labia minora reduction and 22 comparison women who did not. Both
      groups completed a baseline questionnaire (preoperatively for the labiaplasty
      group) and a follow-up questionnaire 6 months later. The questionnaires contained
      standardized measures of genital appearance satisfaction, relationship
      satisfaction, sexual confidence, psychological distress, self-esteem, and life
      satisfaction. RESULTS: Of the 29 women who underwent labiaplasty, the vast
      majority reported that they were "moderately" or "extremely" satisfied with the
      aesthetic (82.8 percent), functional (86.2 percent), and overall (82.8 percent)
      outcomes. For the standardized measures, the only significant change from
      baseline to follow-up for the labiaplasty group relative to the comparison group
      was a reduction in genital appearance dissatisfaction with large effect size (p <
      0.001, d = 3.26). Higher levels of psychological distress (p = 0.001) and having
      a romantic partner (p = 0.016) preoperatively were significantly related to lower
      satisfaction with surgical outcomes. CONCLUSIONS: Labiaplasty appears to have a
      positive effect on women's genital appearance satisfaction, but not their general
      psychological well-being or intimate relationship quality. Medical professionals
      should be mindful of patients with greater psychological distress, as this may
      compromise satisfaction with surgical outcomes. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, II.

PMID- 27879588
TI  - Three-Dimensional Facial Averaging: A Tool for Understanding Facial Aging.
AB  - The progression of facial shape with aging is the subject of various theories and
      assumptions but remains poorly understood. The authors have used the unique
      capabilities of the three-dimensional camera to average the faces of large
      numbers of subjects to understand this complex process. What the authors present
      here is a technique of analysis rather than detailed results.

PMID- 27879589
TI  - Abdominal Contouring: Can the American Society of Anesthesiologists
      Classification System Help Determine When to Say No?
AB  - BACKGROUND: The purpose of this study was to determine whether the American
      Society of Anesthesiologists classification system could be used preoperatively
      to identify patients at high risk for complications after abdominal contouring.
      METHODS: Using the National Surgical Quality Improvement Program database from
      2007 to 2012, patients undergoing abdominal contouring procedures were identified
      and stratified by American Society of Anesthesiologists class. The primary
      outcome was any complication within 30 days. Secondary outcomes included minor
      wound, major surgical, and medical complication. Adjusted odds ratios were
      calculated using logistic regression. RESULTS: A total of 3637 patients were
      analyzed; 14.6 percent of patients were class I, 59.1 percent were class II, 23.4
      percent were class III, and 2.9 percent were class IV. Overall complication and
      mortality rates were 12 percent and 0.2 percent, respectively. There was a
      significant trend of increasing odds of any complication with increasing class
      (class I, OR, 1.0; class II, OR, 1.5; class III, OR, 2.5; class IV, OR, 5.6; p
      trend < 0.001). This trend was seen consistently for minor wound complications,
      medical complications, and major surgical complications (p = 0.007, p = 0.005,
      and p = 0.001, respectively). CONCLUSIONS: The American Society of
      Anesthesiologists classification system, which is simple and universally
      applicable, appears to predict significant complications and can be used to
      rapidly screen patients before abdominal contouring. Furthermore, the authors'
      results can be used to inform patient-physician discussion about the risks
      incurred when undergoing these procedures based on their individual class.
      Together with optimization of high-risk patients, patient selection using
      American Society of Anesthesiologists classification may prevent complications
      and improve outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

PMID- 27879591
TI  - Comparison of Endothelial Differentiation Capacities of Human and Rat Adipose
      Derived Stem Cells.
AB  - BACKGROUND: The authors compared the endothelial differentiation capacities of
      human and rat adipose-derived stem cells to determine whether human adipose
      derived stem cells can be a source of endothelial cells clinically. METHODS:
      Human and rat adipose-derived stem cells were harvested and characterized with
      flow cytometry and trilineage differentiation. Cells from passages III through V
      were fed with endothelial cell differentiation medium for up to 3 weeks. Cells
      were harvested after 1, 2, and 3 weeks, and endothelial differentiation was
      evaluated with quantitative reverse-transcriptase polymerase chain reaction, flow
      cytometry, and angiogenic sprouting assays. RESULTS: Both human and rat adipose
      derived stem cells were CD90, CD44, and CD31 before differentiation. The cells
      were successfully differentiated into adipogenic, osteogenic, and chondrogenic
      lineages. Expression of endothelial cell-specific genes peaked at the second week
      of differentiation in both human and rat cells. The fold changes in expression of
      CD31, vascular endothelial growth factor receptor-1, nitric oxide synthase, and
      von Willebrand factor genes at week 2 were 0.4 +/- 0.1, 34.7 +/- 0.3, 2.03 +/-
      0.25, and 12.5 +/- 0.3 respectively, in human adipose-derived stem cells; and 1.5
      +/- 1.01, 21.6 +/- 1.7, 17.9 +/- 0.6, and 11.2 +/- 1.3, respectively, in rat
      cells. The percentages of CD31 cells were 0.2, 0.64, and 1.6 in human cell
      populations and 0.5, 5.91, and 11.5 in rat cell populations at weeks 1, 2, and 3,
      respectively. Rat adipose-derived stem cell-derived endothelial cells displayed
      enhanced sprouting capability compared with the human cells. CONCLUSIONS: Human
      adipose-derived stem cells responded less strongly to EGM-2MV endothelial
      differentiation medium than did the rat cells. Still, the human cells have the
      potential to become a clinical source of endothelial cells with modifications in
      the differentiation conditions.

PMID- 27879590
TI  - Intravenous Hyaluronidase with Urokinase as Treatment for Rabbit Retinal Artery
      Hyaluronic Acid Embolism.
AB  - BACKGROUND: Although various salvage methods have been proposed to treat
      intraretinal artery hyaluronic acid embolism, their applications are still
      limited by various factors. The authors investigated the effectiveness of
      intravenous hyaluronidase with urokinase for resolving retinal artery hyaluronic
      acid embolism. METHODS: The anatomy of rabbit ophthalmic and fundus arteries
      (retinal and choroid artery) was studied. Approximately 0.35 ml of hyaluronic
      acid was injected into the ophthalmic artery to create a retinal artery embolism
      model. The rabbits were grouped randomly (groups A, B, C, D, E, and F) and given
      hyaluronidase with urokinase intravenously at different postobstruction time
      points (10, 20, 30, 40, 50, and 60 minutes). Saline was given to the control
      group. Fundus vascular (retinal and choroid artery) reperfusion status and the
      effectiveness of the solution on the obstruction of each group were observed for
      5 days. RESULTS: The animal model closely imitated actual hyaluronic acid
      ophthalmic/retinal artery obstructions. Three vascular conditions were observed
      after hyaluronidase with urokinase injection: total, partial, and no reperfusion.
      Groups A, B, and C showed a significantly higher overall solution effectiveness
      rate (total/partial reperfusion) compared with the control group (p = 0.001, p =
      0.001, and p = 0.005, respectively). Solution effectiveness in groups D, E, and F
      showed no difference compared with the control group (p = 0.628, p = 1.000, and p
      = 1.000, respectively). The effectiveness of the solution drops dramatically if
      given after 30 minutes of obstruction. CONCLUSIONS: The authors' method can
      indeed help resolve retinal artery hyaluronic acid obstruction. Intravenous
      hyaluronidase with urokinase technique shows possible potential to become a
      standardized treatment protocol for intraretinal artery hyaluronic acid embolism
      with further clinical tests.

PMID- 27879592
TI  - Reinnervated Split-Muscle Technique for Creating Additional Myoelectric Sites in
      an Animal Model.
AB  - BACKGROUND: This study proposes a novel reinnervated split-muscle operation to
      create additional myoelectric sites as sources of command signals of myoelectric
      prostheses for enhanced dexterous hand-to-wrist motions. The aim of this study
      was to investigate the postprocedure electromyographic properties of the muscles
      as distinct myoelectric sites in a rat model. METHODS: The reinnervated split
      muscle group (n = 6) had the gastrocnemius muscle separated along its
      longitudinal axis and nerves transferred to each new muscle (peroneal nerve to
      lateral muscle head and tibial to medial one); the non-split-muscle group (n = 6)
      only had nerve transfers with its muscle intact. Functional testing was conducted
      after 10 weeks. The main parameter is the difference in mean electromyographic
      amplitude between the new muscles, with greater values indicating better
      separability. RESULTS: After the reinnervated split-muscle procedure, there is a
      significant increase of the average ratio between two muscles compared with the
      control group, from 0.44 (range, 0.02 to 0.86) to 0.77 (range, 0.35 to 0.98) (p =
      0.011). In addition, compared with the non-split muscle group, nerve transfer in
      the split-muscle group is more successful in reaching its intended target muscle.
      CONCLUSION: A reinnervated split-muscle procedure could be beneficial for
      acquiring a more precise and discrete command signal in upper limb amputees, thus
      enabling the creation of more dexterous prosthetic arm.

PMID- 27879593
TI  - Triptolide Reduces the Required Dose of Tacrolimus by Attenuating Inflammation,
      Enhancing Immunosuppression, and Increasing Donor Chimerism in a Heterotopic
      Hindlimb Transplantation Model.
AB  - BACKGROUND: Induction of tolerance and minimizing the toxicity of
      immunosuppression are two fundamental goals in vascularized composite
      allotransplantation. Accumulating data indicate that triptolide is an agent that
      may have the capacity to suppress inflammation and immunologic rejection.
      METHODS: A heterotopic hindlimb allotransplantation model from Brown Norway to
      Lewis rats was established and treated with different doses of tacrolimus
      combined with or without triptolide. Mean survival time of the transplants was
      monitored, and histopathologic examination of the skin was performed. The level
      of inflammatory cytokine interleukin-1beta, interleukin-6, and tumor necrosis
      factor-a in peripheral blood was assayed. The percentage of T lymphocytes and its
      subsets was measured using flow cytometry. The level of recipient peripheral
      chimerism and the apoptosis of donor bone marrow cells were evaluated. The
      apoptotic related genes bcl-2 and Bax were detected by real-time polymerase chain
      reaction. RESULTS: The authors' results showed that triptolide not only reduces
      the dose of tacrolimus required for immunosuppression, but also decreased drug
      side effects in terms of weight gain and diarrhea. Triptolide had an obvious
      effect on proinflammatory cytokine expression and T-lymphocyte proliferation in
      the peripheral blood. Interestingly, triptolide could increase the mixed
      chimerism level of recipients, possibly by inhibiting the apoptosis of
      transplanted bone marrow cells by means of regulation of the apoptotic genes bcl
      2 and Bax. CONCLUSIONS: Triptolide reduces the dose of tacrolimus required for
      immunosuppression by attenuating inflammation and by T-cell suppression.
      Furthermore, triptolide increases the chimerism level, which might contribute to
      acceptance of the allografts.

PMID- 27879594
TI  - Comparison of Ulnar Intrinsic Function following Supercharge End-to-Side Anterior
      Interosseous-to-Ulnar Motor Nerve Transfer: A Matched Cohort Study of Proximal
      Ulnar Nerve Injury Patients.
AB  - BACKGROUND: There are few studies supporting supercharge end-to-side nerve
      transfer for high ulnar nerve injury. The current study hypothesized that
      patients with a supercharge end-to-side anterior interosseous nerve-to-ulnar
      motor nerve transfer would demonstrate superior return of intrinsic function
      compared with conventional treatment only. METHODS: A retrospective matched
      cohort study matched supercharge end-to-side transfer patients based on age,
      level of injury, and mechanism to ulnar nerve injury patients who did not have
      the transfer. The primary outcome was return of ulnar intrinsic function, based
      on clinical examination and/or electromyography. Dichotomous and continuous
      variables were compared with Fisher's exact and t tests, respectively. RESULTS:
      Thirteen supercharge end-to-side patients were identified (>1 year follow-up).
      The average age of both cohorts was 35 years. Ulnar nerve transection above the
      proximal third of the forearm represented 54 percent of patients; compressive
      injuries represented 46 percent. Eleven supercharge end-to-side transfer patients
      (84 percent) demonstrated intrinsic function recovery compared with five (38
      percent) non-supercharge end-to-side patients (p < 0.05). Average time to initial
      motor recovery was similar between the two groups (supercharge end-to-side, 2.9
      months; non-supercharge end-to-side, 3.8 months; p > 0.2). Intrinsic function
      return was more likely following nerve transection with the supercharge end-to
      side procedure (85 percent versus 14 percent; p = 0.03), whereas compression
      injuries had comparable intrinsic function return regardless of the supercharge
      end-to-side transfer (67 percent versus 67 percent; p = 1.0). CONCLUSIONS: This
      matched cohort study demonstrates that the supercharge end-to-side transfer
      results in increased ulnar intrinsic reinnervation following ulnar nerve injury.
      This finding may be most relevant following transection injuries. Improved
      outcomes associated with supercharge end-to-side and ulnar nerve repair warrant
      further investigation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 27879595
TI  - The Effect of Written Information on Recall of Surgical Risks of Carpal Tunnel
      Release Surgery: A Randomized Controlled Study.
AB  - BACKGROUND: Written information has been thought to help patients recall surgical
      risks discussed during the informed consent process, but has not been assessed
      for carpal tunnel release, a procedure with the rare but serious risk of complex
      regional pain syndrome. The authors' objective was to determine whether providing
      a pamphlet would improve patients' ability to remember the risks of surgery.
      METHODS: Sixty patients seen for carpal tunnel release were included in this
      prospective, single-blind, randomized study. Patients received either a written
      pamphlet of the risks of surgery or no additional information following a
      standardized consultation. Two weeks after the initial consultation, patients
      were contacted to assess their risk recall and whether they had read about the
      operation from any source. RESULTS: There was no difference in terms of the
      number of risks recalled between pamphlet (1.33 +/- 1.21) or control groups (1.45
      +/- 1.22; p = 0.73). Recall of infection was better in the pamphlet group (p <
      0.05). No patients remembered complex regional pain syndrome. There was no
      difference in the proportion of people who read additional information about
      carpal tunnel release surgery between the pamphlet (34.8 percent) and control
      groups (21.4 percent; p = 0.39), but reading about carpal tunnel release surgery
      was associated with improved recall (2.45 +/- 1.13 versus 0.77 +/- 0.91; p <
      0.01). CONCLUSIONS: Reading about surgery improved risk recall, but providing
      this information in the form of a pamphlet did not, nor did it affect patients'
      ability to recall the risk of complex regional pain syndrome. These results
      demonstrate that surgeons should implement additional measures to improve
      comprehension of surgical risks. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, I.

PMID- 27879596
TI  - Sleep Architecture Linked to Airway Obstruction and Intracranial Hypertension in
      Children with Syndromic Craniosynostosis.
AB  - BACKGROUND: Children with syndromic craniosynostosis often have obstructive sleep
      apnea and intracranial hypertension. The authors aimed to evaluate (1) sleep
      architecture, and determine whether this is influenced by the presence of
      obstructive sleep apnea and/or intracranial hypertension; and (2) the effect of
      treatment on sleep architecture. METHODS: This study included patients with
      syndromic craniosynostosis treated at a national referral center, undergoing
      screening for obstructive sleep apnea and intracranial hypertension. Obstructive
      sleep apnea was identified by polysomnography, and categorized into no, mild,
      moderate, or severe. Intracranial hypertension was identified by the presence of
      papilledema on funduscopy, supplemented by optical coherence tomography and/or
      intracranial pressure monitoring. Regarding sleep architecture, sleep was divided
      into rapid eye movement or non-rapid eye movement sleep; respiratory effort
      related arousals and sleep efficiency were scored. RESULTS: The authors included
      39 patients (median age, 5.9 years): 19 with neither obstructive sleep apnea nor
      intracranial hypertension, 11 with obstructive sleep apnea (four
      moderate/severe), six with intracranial hypertension, and three with obstructive
      sleep apnea and intracranial hypertension. Patients with syndromic
      craniosynostosis, independent of the presence of mild obstructive sleep apnea
      and/or intracranial hypertension, have normal sleep architecture compared with
      age-matched controls. Patients with moderate/severe obstructive sleep apnea have
      a higher respiratory effort-related arousal index (p < 0.01), lower sleep
      efficiency (p = 0.01), and less rapid eye movement sleep (p = 0.04). An
      improvement in sleep architecture was observed following monobloc surgery (n = 5;
      rapid eye movement sleep, 5.3 percent; p = 0.04). CONCLUSIONS: Children with
      syndromic craniosynostosis have in principle normal sleep architecture. However,
      moderate/severe obstructive sleep apnea does lead to disturbed sleep
      architecture, which fits within a framework of a unifying theory for obstructive
      sleep apnea, intracranial hypertension, and sleep. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Risk, II.

PMID- 27879597
TI  - Discussion: Sleep Architecture Linked to Airway Obstruction and Intracranial
      Hypertension in Children with Syndromic Craniosynostosis.

PMID- 27879598
TI  - Alveolar Bone Grafting and Cleft Lip and Palate: A Review.
AB  - Alveolar bone grafting in the mixed dentition stage is an accepted step in the
      management of cleft alveoli, providing maxillary arch support for dentition and
      mastication. Points of contention regarding best practices remain, including
      specific timing, perioperative orthodontic management, bone harvest and
      substitutes, pain management, and outcomes evaluations. SCOPUS and MEDLINE were
      searched for articles about alveolar bone grafting, which were read independently
      by two authors and selected for inclusion on the basis of relevance and merit.
      Articles on which recommendations were based were rated using the methodological
      index for non-randomized studies criteria. Three hundred thirty-three distinct
      articles were found, of which 64 were found to be suitable and relevant for
      inclusion. The average methodological index for non-randomized studies score was
      10.39, with an interrater weighted kappa of 0.7301. Prospective comparative
      studies about alveolar bone grafting are rare, but available evidence suggests
      grafting before canine eruption with targeted preoperative orthopedic
      interventions, the continued use of iliac crest corticocancellous autologous
      graft, and adjunctive pain control methods. Greater consensus must be reached
      about valuable outcome measures for research, including use of imaging and
      indications for regrafting following graft failure.

PMID- 27879599
TI  - Total Human Eye Allotransplantation: Developing Surgical Protocols for Donor and
      Recipient Procedures.
AB  - BACKGROUND: Vascularized composite allotransplantation of the eye is an
      appealing, novel method for reconstruction of the nonfunctioning eye. The
      authors' group has established the first orthotopic model for eye transplantation
      in the rat. With advancements in immunomodulation strategies together with new
      therapies in neuroregeneration, parallel development of human surgical protocols
      is vital for ensuring momentum toward eye transplantation in actual patients.
      METHODS: Cadaveric donor tissue harvest (n = 8) was performed with orbital
      exenteration, combined open craniotomy, and endonasal approach to ligate the
      ophthalmic artery with a cuff of paraclival internal carotid artery, for
      transection of the optic nerve at the optic chiasm and transection of cranial
      nerves III to VI and the superior ophthalmic vein at the cavernous sinus.
      Candidate recipient vessels (superficial temporal/internal maxillary/facial
      artery and superficial temporal/facial vein) were exposed. Vein grafts were
      required for all anastomoses. Donor tissue was secured in recipient orbits
      followed by sequential venous and arterial anastomoses and nerve coaptation.
      Pedicle lengths and calibers were measured. All steps were timed, photographed,
      video recorded, and critically analyzed after each operative session. RESULTS:
      The technical feasibility of cadaveric donor procurement and transplantation to
      cadaveric recipient was established. Mean measurements included optic nerve
      length (39 mm) and caliber (5 mm), donor artery length (33 mm) and caliber (3
      mm), and superior ophthalmic vein length (15 mm) and caliber (0.5 mm). Recipient
      superficial temporal, internal maxillary artery, and facial artery calibers were
      0.8, 2, and 2 mm, respectively; and superior temporal and facial vein calibers
      were 0.8 and 2.5 mm, respectively. CONCLUSION: This surgical protocol serves as a
      benchmark for optimization of technique, large-animal model development, and
      ultimately potentiating the possibility of vision restoration transplantation
      surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 27879600
TI  - Discussion: Total Human Eye Allotransplantation: Developing Surgical Protocols
      for Donor and Recipient Procedures.

PMID- 27879601
TI  - Discussion: Variations in Frontonasal Flap Design for Single-Stage Reconstruction
      of the Nasal Tip.

PMID- 27879602
TI  - Health-Related Quality of Life following Reconstruction for Common Head and Neck
      Surgical Defects.
AB  - BACKGROUND: Improved understanding and management of health-related quality of
      life represents one of the greatest unmet needs for patients with head and neck
      malignancies. The purpose of this study was to prospectively measure health
      related quality of life associated with different anatomical (head and neck)
      surgical resections. METHODS: A prospective analysis of health-related quality of
      life was performed in patients undergoing surgical resection with flap
      reconstruction for stage II or III head and neck malignancies. Patients completed
      the European Organization for Research and Treatment of Cancer Core Quality-of
      Life Questionnaire-30 and the European Organization for Research and Treatment of
      Cancer Head and Neck Cancer Module-35 preoperatively, and at set postoperative
      time points. Scores were compared with a paired t test. RESULTS: Seventy-five
      patients were analyzed. The proportion of the cohort not alive at 2 years was 53
      percent. Physical, role, and social functioning scores at 3 months were
      significantly lower than preoperative values (p < 0.05). At 12 months
      postoperatively, none of the function or global quality-of-life scores differed
      from preoperative levels, whereas five of the symptom scales remained below
      baseline. At 1 year postoperatively, maxillectomy, partial glossectomy, and oral
      lining defects had better function and fewer symptoms than mandibulectomy,
      laryngectomy, and total glossectomy. From 6 to 12 months postoperatively, partial
      glossectomy and oral lining defects had greater global quality of life than
      laryngectomies (p < 0.05). CONCLUSIONS: Postoperative health-related quality of
      life is associated with the anatomical location of the head and neck surgical
      resection. Preoperative teaching should be targeted for common ablative defects,
      with postoperative expectations adjusted appropriately. Because surgery
      negatively impacts health-related quality of life in the immediate postoperative
      period, the limited survivorship should be reviewed with patients. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 27879603
TI  - Discussion: Evaluation of the Upper Limb Lymphatic System: A Prospective
      Lymphoscintigraphic Study in Melanoma Patients and Healthy Controls.

PMID- 27879604
TI  - Effects of Incisional Negative-Pressure Wound Therapy on Primary Closed Defects
      after Superficial Circumflex Iliac Artery Perforator Flap Harvest: Randomized
      Controlled Study.
AB  - BACKGROUND: Prolonged hematoma or seroma after primary closure is a causative
      element in wound complications. This study evaluated the effects of negative
      pressure wound therapy on primary closed wounds after superficial circumflex
      iliac artery perforator flap harvest. METHODS: This study was a prospective,
      randomized, clinical trial comparing conventional dressing against a single
      application of negative-pressure wound therapy for 5 days after primary closure.
      A total of 100 patients who had superficial circumflex iliac artery perforator
      flap harvest were enrolled. RESULTS: There was no statistical difference between
      the incisional negative-pressure wound therapy and conventional dressing groups
      in the distribution of risk factors. Significant findings were noted for duration
      and amount of closed suction drainage: 6.12 +/- 4.99 days (median, 4 days; range,
      3 to 8 days) and 100.47 +/- 140.69 cc (median, 42 cc) for wounds treated with
      conventional dressing versus 3.34 +/- 1.35 days (median, 3 days; range, 2 to 4
      days) and 23.28 +/-18.36 cc (median, 20 cc) for wounds in treatment group (p =
      0.0077 and p = 0.0004), respectively. After closure, an increase in skin
      perfusion were noted on day 5 in the treatment group (p = 0.0223). There was one
      case of wound dehiscence in the conventional dressing group. CONCLUSION: The
      incisional negative-pressure wound therapy has a positive effect over primary
      closed surgical defects by significantly reducing the amount of fluid collected
      by closed suction drains, allowing earlier removal of drains and enhancing the
      skin perfusion on the repaired skin. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 27879605
TI  - Discussion: Effects of Incisional Negative-Pressure Wound Therapy on Primary
      Closed Defects after Superficial Circumflex Iliac Artery Perforator Flap Harvest:
      Randomized Controlled Study.

PMID- 27879606
TI  - Improving Outcomes in Tendon Repair: A Critical Look at the Evidence for Flexor
      Tendon Repair and Rehabilitation.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Appreciate the variation and evolution of flexor tendon management 2. Know
      how to assess the patient who presents with a flexor tendon laceration. 3.
      Understand the biology of repairing flexor tendon lacerations. 4. Appreciate the
      technical challenges in flexor tendon repair relating to different zones. 5.
      Understand the rationale of postoperative hand therapy. 6. Have an overview of
      the types of secondary tendon surgery. BACKGROUND: Flexor tendon injury
      constitutes a considerable trauma workload for hand surgeons, and a vast amount
      of research is dedicated toward improving outcomes in tendon repair. This
      Continuing Medical Education article aims to provide an up-to-date evidence-based
      outline of flexor tendon surgery in the hand. METHODS: The authors reviewed the
      literature on flexor tendon repairs to include a balanced overview of the
      experimental and clinical research. For each section, the best levels of evidence
      were assessed in the context of past research to provide a comprehensive opinion
      on best management. RESULTS: The review highlights current trends in flexor
      tendon surgery, clinical assessment, anesthetic technique, surgical approach,
      repair technique, and rehabilitation. Carefully selected illustrations, figures,
      tables, and video have been used to supplement the findings of the review.
      CONCLUSIONS: Early active mobilization remains the only long-term proven strategy
      to improve outcomes. Incorporating intraoperative mobilization using "wide-awake"
      surgery could emerge to further improve tendon outcomes. Good surgical approach,
      meticulous surgery, up-to-date physiotherapy regimens, and patient education
      remain the cornerstone of obtaining best outcomes.

PMID- 27879607
TI  - #PlasticSurgery.
AB  - BACKGROUND: Social media use is growing inexorably, and there is public appetite
      for evidence-based information. Little is known about engagement by plastic
      surgeons with social media. The aim of this study was to examine posting about
      plastic surgery on Twitter, to best inform how board-certified plastic surgeons
      could use the hashtag #PlasticSurgery as a tool to educate patients and the
      public. METHODS: A prospective analysis of 2880 "tweets" containing the words
      "plastic surgery" was performed. The following were assessed: identity of author,
      use of the hashtag #PlasticSurgery, subject matter, whether link to study was
      provided, and whether posts by surgeons were self-promotional or educational.
      RESULTS: Social media posting about plastic surgery is dominated by the public,
      accounting for 70.6 percent of posts versus only 6.0 percent by plastic surgeons.
      Only 5.4 percent of all tweets contained the hashtag #PlasticSurgery, although
      almost half of those that did were by plastic surgeons. Of these, 61.3 percent of
      posts by plastic surgeons were about aesthetic surgery; additional posts were
      about basic science, patient safety, and reconstruction (13.9, 4.0, and 2.3
      percent, respectively). Eighteen scientific articles were referenced, with a link
      to the Journal site posted in two tweets. Of posts by plastic surgeons, 37.0
      percent were self-promotional. CONCLUSIONS: The American Society of Plastic
      Surgeons and its Journal have recognized that social media may be used to educate
      and engage. Board-certified plastic surgeons have a great opportunity to promote
      evidence-based plastic practice by means of #PlasticSurgery in the interests of
      supporting patients and the profession.

PMID- 27879608
TI  - E-Cigarettes and Potential Implications for Plastic Surgery.
AB  - The use of tobacco-based products, most notably cigarettes, is related directly
      to wound healing problems and poorer outcomes in plastic surgery. Current
      abstracts have highlighted the potential complications from nicotine,
      specifically following plastic surgery in patients who choose to smoke. Recently,
      products that use electricity to vaporize liquid nitrogen have been gaining
      popularity. New rules were recently proposed that would give the federal
      government authority over electronic cigarettes. However, the health-related
      issues surrounding e-cigarettes are still largely unknown or misunderstood. These
      issues also extend to their impact on surgical procedures, notably their effect
      on plastic surgical procedures that rely heavily on the vascularity of either the
      host wound bed or the replacement tissue.

PMID- 27879609
TI  - Medical Accreditation in the United States: What For?

PMID- 27879612
TI  - Limited Panniculectomy for Adult Buried Penis Repair.

PMID- 27879613
TI  - Reply: Limited Panniculectomy for Adult Buried Penis Repair.

PMID- 27879614
TI  - Getting a better look: Outcomes of laparoscopic versus transdiaphragmatic
      pericardial window for penetrating thoracoabdominal trauma at a Level I trauma
      center.
AB  - BACKGROUND: In penetrating thoracoabdominal trauma, it is necessary to evaluate
      both the pericardial fluid and the diaphragm directly. Transdiaphragmatic
      pericardial windows (TDWs) provide direct access to the pericardium and diaphragm
      but expose the patient to the risks of laparotomy. We hypothesize that
      transabdominal laparoscopic pericardial windows (LPWs) are a safe and effective
      alternative to TDWs in stable patients. METHODS: This is a retrospective
      observational study of stable patients with thoracoabdominal penetrating trauma
      at a level I trauma center between January 2007 and June 2015, comparing outcomes
      after TDW versus LPW. RESULTS: A total of 99 patients with penetrating trauma had
      a diagnostic pericardial window, 33 of which were laparoscopic. Stab wounds were
      most common (80, 80.8%) compared with gunshot wounds (19, 19.2%). Of 11 patients
      who had a positive pericardial window, 10 (90.9%) were associated with a cardiac
      injury. There was no difference in the ratio of positive pericardial windows for
      patients who had TDW versus LPW (8/66, 12.1% vs. 3/33, 9.1%; p = 0.651). One
      patient had a complication related to a negative pericardial window in the
      laparoscopic group. There was no difference in complication rates between TDW and
      LPW (p = 0.155). Mean length of stay was longer in TDW compared with LPW (12 vs.
      5 days, p = 0.046). One patient died during index admission in the TDW group, but
      there was no difference in mortality rates between TDW and LPW during the index
      admission (p = 0.477). Median length of follow-up was 29 days (range, 0-2,709).
      On long-term follow-up, there was also no difference in mortality rates between
      TDW and LPW (2/66, 3.0% vs. 2/33, 6.1%; p = 0.470). CONCLUSION: In
      hemodynamically stable patients with thoracoabdominal injuries, LPW is a safe and
      effective technique in evaluating both pericardial fluid and the diaphragm. LPW
      is a viable alternative to exploratory laparotomy and TDWs. LEVEL OF EVIDENCE:
      Therapeutic study, level IV.

PMID- 27879618
TI  - The Value of Detecting Asymptomatic Signs of Myocardial Ischemia in Patients With
      Coronary Artery Disease in Outpatient Cardiac Rehabilitation.
AB  - BACKGROUND: Electrocardiographic (ECG) monitored outpatient cardiac
      rehabilitation (OP-CR) is routinely performed following a variety of
      cardiovascular procedures and conditions. OBJECTIVE: The aim of this study is to
      determine if diagnostic-quality ECG monitoring in patients with coronary artery
      disease (CAD) during OP-CR is useful in identifying asymptomatic myocardial
      ischemia, resulting in change(s) in care or medical management. METHODS: A
      retrospective analysis of ECG monitoring was done on all OP-CR patients diagnosed
      with CAD (n = 1213) from January 2000 through June 2013. RESULTS: Nearly a
      quarter of the patients (24%; n = 288) displayed at least 1 mm of asymptomatic ST
      segment depression at 80 milliseconds after the J-point during at least 1 session
      of OP-CR. Of these patients, 57% had medical management change(s) compared with
      24% for those who did not show ECG changes suggesting ischemia (P < .0001). In
      patients with asymptomatic ischemia having medical management change(s), 84%
      resulted directly from OP-CR staff detection. Fewer patients diagnosed with
      myocardial infarction and coronary artery bypass graft surgery demonstrated ECG
      signs of ischemia, whereas more patients diagnosed with stable angina and
      percutaneous coronary interventions demonstrated ECG signs of ischemia.
      CONCLUSION: This study demonstrates that most patients with CAD showing
      asymptomatic ECG signs suggesting ischemia undergo medical management change(s)
      as a result of the finding. Diagnostic-quality ECG monitoring during OP-CR
      appears warranted in this population.

PMID- 27879619
TI  - Bloody Epiphora (Hemolacria) Years After Repair of Orbital Floor Fracture.
AB  - Surgical repair of orbital fractures with implants is a widely used treatment
      modality. While a variety of established complications are associated with this
      technique, most are directly understood and treated. Bloody epiphora is a finding
      with potentially ominous causes. The authors present a unique case of bloody
      epiphora, accompanied by orbital hemorrhage arising several years after orbital
      floor fracture repair, due to erosion of the nasolacrimal drainage system by a
      displaced implant combined with anticoagulation. The collection and evaluation of
      all protected patient health information was compliant with the regulations and
      conditions set forth in the Health Insurance Portability and Availability Act of
      1996.

PMID- 27879620
TI  - Recurrent Orbital Inflammation Mimicking Orbital Cellulitis Associated With
      Orbitopalpebral Venous Lymphatic Malformation.
AB  - An 8-year-old boy initially presented with an orbitopalpebral mass diagnosed
      clinically and radiologically as a low-flow diffuse venous lymphatic malformation
      involving the left upper eyelid and orbit. Over 8 months of follow up, he had 2
      acute episodes of severe orbital inflammation that warranted hospitalization and
      treatment with intravenous antibiotic, steroids and surgical debulking. After a
      third surgical excision, the lesion remained clinically stable.

PMID- 27879621
TI  - Online Ratings of ASOPRS Surgeons: What Do Your Patients Really Think of You?
AB  - PURPOSE: To characterize patient evaluations of American Society of Ophthalmic
      Plastic and Reconstructive Surgery (ASOPRS) surgeons on a popular online
      physician rating website in an effort to determine which factors play a role in
      determining the likelihood of a patient recommending an ASOPRS surgeon to family
      and friends. METHODS: After obtaining approval and access from Healthgrades.com,
      the website database was searched for 612 U.S.-based ASOPRS members using their
      name as published on http://www.asoprs.org/ as of May 2015. For each surgeon, the
      total number of ratings and average ratings were recorded under each category.
      The evaluator recommendation, defined as the response to the questions of
      "likelihood of recommending Dr. X to family and friends," constituted the main
      outcome measure. Variables from each surgeon were compared using unpaired t
      tests, with statistical significance set at p < 0.05. Correlations were analyzed
      using Spearman correlation (rs), with coefficients of greater than or equal to
      0.40 or less than or equal to -0.40 considered significant. RESULTS: Five-hundred
      nineteen members (85%) had at least 1 rating while 222 members (36%) had 10 or
      more ratings. The mean number of ratings for all rated members was 11.4 (range, 1
      77; standard deviation [SD] = 11.1) and mean evaluator recommendation score was
      4.16 (range, 1-5; SD = 0.79). There was a strong negative correlation between
      total wait time and evaluator recommendation score (rs = -0.409, p < 0.001). The
      average number of ratings and rating scores for all categories were not
      significantly different when comparing male with female members. University
      employed members had significantly fewer ratings (8.46; range, 1-52; SD = 9.3)
      compared with other members (11.9; range, 1-77; SD = 11.3) (p < 0.016). There
      were no differences in any other rating score when comparing those university
      employed members with other members. CONCLUSION: Online patient-reported
      evaluations of ASOPRS surgeons appear high in many categories. Long wait times
      correlate strongly with lower recommendation scores. Further study is required to
      determine how online patient reviews correlate to objective outcome measures, and
      how these reviews affect surgeon selection by patients.

PMID- 27879622
TI  - Ultrasound-Assisted Extraction, Centrifugation and Ultrafiltration: Multistage
      Process for Polyphenol Recovery from Purple Sweet Potatoes.
AB  - This work provides an evaluation of an ultrasound-assisted, combined extraction,
      centrifugation and ultrafiltration process for the optimal recovery of
      polyphenols. A purple sweet potato (PSP) extract has been obtained using
      ultrasonic circulating extraction equipment at a power of 840 W, a frequency of
      59 kHz and using water as solvent. Extract ultrafiltration, using
      polyethersulfone (PES), was carried out for the recovery of polyphenol, protein
      and anthocyanin. Pre-treatment, via the centrifugation of purple sweet potato
      extract at 2500 rpm over 6 min, led to better polyphenol recovery, with
      satisfactory protein removal (reused for future purposes), than PSP extract
      filtration without centrifugation. Results showed that anthocyanin was
      efficiently recovered (99%) from permeate. The exponential model fit well with
      the experimental ultrafiltration data and led to the calculation of the
      membrane's fouling coefficient. The optimization of centrifugation conditions
      showed that, at a centrifugation speed of 4000 rpm (1195* g) and duration of 7.74
      min, the optimized polyphenol recovery and fouling coefficient were 34.5% and
      29.5 m-1, respectively. The removal of proteins in the centrifugation process
      means that most of the anthocyanin content (90%) remained after filtration. No
      significant differences in the intensities of the HPLC-DAD-ESI-MS2 peaks were
      found in the samples taken before and after centrifugation for the main
      anthocyanins; peonidin-3-feruloylsophoroside-5-glucoside, peonidin-3-caffeoyl-p
      hydroxybenzoylsophoroside-5-glucoside, and peonidin-3-caffeoyl-feruloyl
      sophoroside-5-glucoside. This proves that centrifugation is an efficient method
      for protein removal without anthocyanin loss. This study considers this process
      an ultrasound-assisted extraction-centrifugation-ultrafiltration for purple sweet
      potato valorization in "green" technology.

PMID- 27879623
TI  - Dynamic Duos? Jamaican Fruit Bats (Artibeus jamaicensis) Do Not Show Prosocial
      Behavior in a Release Paradigm.
AB  - Once thought to be uniquely human, prosocial behavior has been observed in a
      number of species, including vampire bats that engage in costly food-sharing.
      Another social chiropteran, Jamaican fruit bats (Artibeus jamaicensis), have been
      observed to engage in cooperative mate guarding, and thus might be expected to
      display prosocial behavior as well. However, frugivory and hematophagy diets may
      impose different selection pressures on prosocial preferences, given that
      prosocial preferences may depend upon cognitive abilities selected by different
      ecological constraints. Thus, we assessed whether Jamaican fruit bats would
      assist a conspecific in an escape paradigm in which a donor could opt to release
      a recipient from an enclosure. The test apparatus contained two compartments-one
      of which was equipped with a sensor that, once triggered, released the trap door
      of the adjacent compartment. Sixty-six exhaustive pairs of 12 bats were tested,
      with each bat in each role, twice when the recipient was present and twice when
      absent. Bats decreased their behavior of releasing the trapdoor in both
      conditions over time, decreasing the behavior slightly more rapidly in the
      recipient absent condition. Bats did not release the door more often when
      recipients were present, regardless of the recipient; thus, there was no clear
      evidence of prosocial behavior.

PMID- 27879625
TI  - Towards Camera-LIDAR Fusion-Based Terrain Modelling for Planetary Surfaces:
      Review and Analysis.
AB  - In recent decades, terrain modelling and reconstruction techniques have increased
      research interest in precise short and long distance autonomous navigation,
      localisation and mapping within field robotics. One of the most challenging
      applications is in relation to autonomous planetary exploration using mobile
      robots. Rovers deployed to explore extraterrestrial surfaces are required to
      perceive and model the environment with little or no intervention from the ground
      station. Up to date, stereopsis represents the state-of-the art method and can
      achieve short-distance planetary surface modelling. However, future space
      missions will require scene reconstruction at greater distance, fidelity and
      feature complexity, potentially using other sensors like Light Detection And
      Ranging (LIDAR). LIDAR has been extensively exploited for target detection,
      identification, and depth estimation in terrestrial robotics, but is still under
      development to become a viable technology for space robotics. This paper will
      first review current methods for scene reconstruction and terrain modelling using
      cameras in planetary robotics and LIDARs in terrestrial robotics; then we will
      propose camera-LIDAR fusion as a feasible technique to overcome the limitations
      of either of these individual sensors for planetary exploration. A comprehensive
      analysis will be presented to demonstrate the advantages of camera-LIDAR fusion
      in terms of range, fidelity, accuracy and computation.

PMID- 27879624
TI  - Transcriptome Analysis Identifies Key Candidate Genes Mediating Purple Ovary
      Coloration in Asiatic Hybrid Lilies.
AB  - Lily tepals have a short lifespan. Once the tepals senesce, the ornamental value
      of the flower is lost. Some cultivars have attractive purple ovaries and fruits
      which greatly enhance the ornamental value of Asiatic hybrid lilies. However,
      little is known about the molecular mechanisms of anthocyanin biosynthesis in
      Asiatic hybrid lily ovaries. To investigate the transcriptional network that
      governs purple ovary coloration in Asiatic hybrid lilies, we obtained
      transcriptome data from green ovaries (S1) and purple ovaries (S2) of Asiatic
      "Tiny Padhye". Comparative transcriptome analysis revealed 4228 differentially
      expressed genes. Differential expression analysis revealed that ten unigenes
      including four CHS genes, one CHI gene, one F3H gene, one F3'H gene, one DFR
      gene, one UFGT gene, and one 3RT gene were significantly up-regulated in purple
      ovaries. One MYB gene, LhMYB12-Lat, was identified as a key transcription factor
      determining the distribution of anthocyanins in Asiatic hybrid lily ovaries.
      Further qPCR results showed unigenes related to anthocyanin biosynthesis were
      highly expressed in purple ovaries of three purple-ovaried Asiatic hybrid lilies
      at stages 2 and 3, while they showed an extremely low level of expression in
      ovaries of three green-ovaried Asiatic hybrid lilies during all developmental
      stages. In addition, shading treatment significantly decreased pigment
      accumulation by suppressing the expression of several unigenes related to
      anthocyanin biosynthesis in ovaries of Asiatic "Tiny Padhye". Lastly, a total of
      15,048 Simple Sequence Repeats (SSRs) were identified in 13,710 sequences, and
      primer pairs for SSRs were designed. The results could further our understanding
      of the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily
      ovaries.

PMID- 27879626
TI  - Smart Toys Designed for Detecting Developmental Delays.
AB  - In this paper, we describe the design considerations and implementation of a
      smart toy system, a technology for supporting the automatic recording and
      analysis for detecting developmental delays recognition when children play using
      the smart toy. To achieve this goal, we take advantage of the current commercial
      sensor features (reliability, low consumption, easy integration, etc.) to develop
      a series of sensor-based low-cost devices. Specifically, our prototype system
      consists of a tower of cubes augmented with wireless sensing capabilities and a
      mobile computing platform that collect the information sent from the cubes
      allowing the later analysis by childhood development professionals in order to
      verify a normal behaviour or to detect a potential disorder. This paper presents
      the requirements of the toy and discusses our choices in toy design, technology
      used, selected sensors, process to gather data from the sensors and generate
      information that will help in the decision-making and communication of the
      information to the collector system. In addition, we also describe the play
      activities the system supports.

PMID- 27879628
TI  - Carbon-Based Materials for Photo-Triggered Theranostic Applications.
AB  - Carbon-based nanomaterials serve as a type of smart material for photo-triggered
      disease theranostics. The inherent physicochemical properties of these
      nanomaterials facilitate their use for less invasive treatments. This review
      summarizes the properties and applications of materials including fullerene,
      nanotubes, nanohorns, nanodots and nanographenes for photodynamic nanomedicine in
      cancer and antimicrobial therapies. Carbon nanomaterials themselves do not
      usually act as photodynamic therapy (PDT) agents owing to the high
      hydrophobicity, however, when the surface is passivated or functionalized, these
      materials become great vehicles for PDT. Moreover, conjugation of carbonaceous
      nanomaterials with the photosensitizer (PS) and relevant targeting ligands
      enhances properties such as selectivity, stability, and high quantum yield,
      making them readily available for versatile biomedical applications.

PMID- 27879627
TI  - Dietary Intake, Body Composition, and Menstrual Cycle Changes during Competition
      Preparation and Recovery in a Drug-Free Figure Competitor: A Case Study.
AB  - Physique competitions are events in which competitors are judged on muscular
      appearance and symmetry. The purpose of this retrospective case study was to
      describe changes in dietary intake, body mass/composition, and the menstrual
      cycle during the 20-week competition preparation (PREP) and 20-week post
      competition recovery (REC) periods of a drug-free amateur female figure
      competitor (age = 26-27, BMI = 19.5 kg/m2). Dietary intake (via weighed food
      records) and body mass were assessed daily and averaged weekly. Body composition
      was estimated via Dual-energy X-ray absorptiometry (DXA) and 7-site skinfold
      measurements. Energy intake, body mass and composition, and energy availability
      decreased during the 20-week PREP period (changes of ~298 kcals, 5.1 kg, 6.5%
      body fat, and 5.4 kcal/kg fat free mass, respectively) and returned to baseline
      values by end of the 20-week REC period. Menstrual cycle irregularity was
      reported within the first month of PREP and the last menstruation was reported at
      week 11 of PREP. Given the potentially adverse health outcomes associated with
      caloric restriction, future, prospective cohort studies on the physiological
      response to PREP and REC are warranted in drug-free, female physique competitors.

PMID- 27879629
TI  - Erratum: Tahara, M., et al. Measles Virus Hemagglutinin Protein Epitopes: The
      Basis of Antigenic Stability. Viruses 2016, 8, 216.
AB  - The authors wish to make the following change to their paper [1].[...].

PMID- 27879631
TI  - Specialized Rehabilitation Programs for Children and Adolescents with Severe
      Disabling Chronic Pain: Indications, Treatment and Outcomes.
AB  - Children and adolescents with highly disabling chronic pain of high intensity and
      frequency are admitted to specialized pain rehabilitation programs. Some barriers
      to obtaining this specialized care include a lack of availability of treatment
      centers, a perceived social stigma and individual barriers such as socioeconomic
      status. Specialized rehabilitation programs for severe disabling chronic pain
      worldwide have similarities regarding admission criteria, structure and
      therapeutic orientation. They differ, however, regarding their exclusion criteria
      and program descriptions. The short- and long-term effectiveness of some
      rehabilitation programs is well documented. All countries should promote the
      establishment of future pediatric pain centers to improve the health care of
      children and adolescents suffering from severe chronic pain. Standardized
      reporting guidelines should be developed to describe treatments and outcomes to
      enable comparability across treatment centers.

PMID- 27879630
TI  - Recombinant Alpha, Beta, and Epsilon Toxins of Clostridium perfringens:
      Production Strategies and Applications as Veterinary Vaccines.
AB  - Clostridium perfringens is a spore-forming, commensal, ubiquitous bacterium that
      is present in the gastrointestinal tract of healthy humans and animals. This
      bacterium produces up to 18 toxins. The species is classified into five
      toxinotypes (A-E) according to the toxins that the bacterium produces: alpha,
      beta, epsilon, or iota. Each of these toxinotypes is associated with myriad
      different, frequently fatal, illnesses that affect a range of farm animals and
      humans. Alpha, beta, and epsilon toxins are the main causes of disease.
      Vaccinations that generate neutralizing antibodies are the most common
      prophylactic measures that are currently in use. These vaccines consist of
      toxoids that are obtained from C. perfringens cultures. Recombinant vaccines
      offer several advantages over conventional toxoids, especially in terms of the
      production process. As such, they are steadily gaining ground as a promising
      vaccination solution. This review discusses the main strategies that are
      currently used to produce recombinant vaccines containing alpha, beta, and
      epsilon toxins of C. perfringens, as well as the potential application of these
      molecules as vaccines for mammalian livestock animals.

PMID- 27879634
TI  - Expanding the Detection of Traversable Area with RealSense for the Visually
      Impaired.
AB  - The introduction of RGB-Depth (RGB-D) sensors into the visually impaired people
      (VIP)-assisting area has stirred great interest of many researchers. However, the
      detection range of RGB-D sensors is limited by narrow depth field angle and
      sparse depth map in the distance, which hampers broader and longer traversability
      awareness. This paper proposes an effective approach to expand the detection of
      traversable area based on a RGB-D sensor, the Intel RealSense R200, which is
      compatible with both indoor and outdoor environments. The depth image of
      RealSense is enhanced with IR image large-scale matching and RGB image-guided
      filtering. Traversable area is obtained with RANdom SAmple Consensus (RANSAC)
      segmentation and surface normal vector estimation, preliminarily. A seeded
      growing region algorithm, combining the depth image and RGB image, enlarges the
      preliminary traversable area greatly. This is critical not only for avoiding
      close obstacles, but also for allowing superior path planning on navigation. The
      proposed approach has been tested on a score of indoor and outdoor scenarios.
      Moreover, the approach has been integrated into an assistance system, which
      consists of a wearable prototype and an audio interface. Furthermore, the
      presented approach has been proved to be useful and reliable by a field test with
      eight visually impaired volunteers.

PMID- 27879636
TI  - Chiral Hypervalent, Pentacoordinated Phosphoranes.
AB  - This review presents synthetic procedures applied to the preparation of chiral
      (mainly optically active) pentacoordinated, hypervalent mono and bicyclic
      phosphoranes. The mechanisms of their stereoisomerization and their selected
      interconversions are also presented.

PMID- 27879635
TI  - A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue
      Engineering.
AB  - Biodegradable, stimuli-responsive polymers are essential platforms in the field
      of drug delivery and injectable biomaterials for application of bone tissue
      engineering. Various thermo-responsive hydrogels display water-based homogenous
      properties to encapsulate, manipulate and transfer its contents to the
      surrounding tissue, in the least invasive manner. The success of bioengineered
      injectable tissue modified delivery systems depends significantly on their
      chemical, physical and biological properties. Irrespective of shape and defect
      geometry, injectable therapy has an unparalleled advantage in which intricate
      therapy sites can be effortlessly targeted with minimally invasive procedures.
      Using material testing, it was found that properties of stimuli-responsive
      hydrogel systems enhance cellular responses and cell distribution at any site
      prior to the transitional phase leading to gelation. The substantially hydrated
      nature allows significant simulation of the extracellular matrix (ECM), due to
      its similar structural properties. Significant current research strategies have
      been identified and reported to date by various institutions, with particular
      attention to thermo-responsive hydrogel delivery systems, and their pertinent
      focus for bone tissue engineering. Research on future perspective studies which
      have been proposed for evaluation, have also been reported in this review,
      directing considerable attention to the modification of delivering natural and
      synthetic polymers, to improve their biocompatibility and mechanical properties.

PMID- 27879632
TI  - Fish Immunoglobulins.
AB  - The B cell receptor and secreted antibody are at the nexus of humoral adaptive
      immunity. In this review, we summarize what is known of the immunoglobulin genes
      of jawed cartilaginous and bony fishes. We focus on what has been learned from
      genomic or cDNA sequence data, but where appropriate draw upon protein,
      immunization, affinity and structural studies. Work from major aquatic model
      organisms and less studied comparative species are both included to define what
      is the rule for an immunoglobulin isotype or taxonomic group and what exemplifies
      an exception.

PMID- 27879637
TI  - Temperature-Triggered Switchable Helix-Helix Inversion of Poly(phenylacetylene)
      Bearing l-Valine Ethyl Ester Pendants and Its Chiral Recognition Ability.
AB  - A phenylacetylene containing the l-valine ethyl ester pendant (PAA-Val) was
      synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh4) to produce
      the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA
      Val showed a unique temperature-triggered switchable helix-sense in chloroform,
      while it was not observed in highly polar solvents, such as N,N'
      dimethylformamide (DMF). By heating the solution of PPAA-Val in chloroform, the
      sign of the CD absorption became reversed, but recovered after cooling the
      solution to room temperature. Even after six cycles of the heating-cooling
      treatment, the helix sense of the PPAA-Val's backbone was still switchable
      without loss of the CD intensity. The PPAA-Val was then coated on silica gel
      particles to produce novel chiral stationary phases (CSPs) for high-performance
      liquid chromatography (HPLC). These novel PPAA-Val based CSPs showed a high
      chiral recognition ability for racemic mandelonitrile (alpha = 2.18) and racemic
      trans-N,N'-diphenylcyclohexane-1,2-dicarboxamide (alpha = 2.60). Additionally,
      the one-handed helical cis-polyene backbone of PPAA-Val was irreversibly
      destroyed to afford PPAA-Val-H by heating in dimethyl sulfoxide (DMSO)
      accompanied by the complete disappearance of the Cotton effect. Although PPAA-Val
      H had the same l-valine ethyl ester pendants as its cis-isomer PPAA-Val, it
      showed no chiral recognition. It was concluded that the one-handed helical cis
      polyene backbone of PPAA-Val plays an important role in the chiral recognition
      ability.

PMID- 27879638
TI  - Structural Investigation of Cell Wall Xylan Polysaccharides from the Leaves of
      Algerian Argania spinosa.
AB  - Xylan-type polysaccharides were isolated from the leaves of Argania spinosa (L.)
      Skeels collected in the Tindouf area (southwestern Algeria). Xylan fractions were
      obtained by sequential alkaline extractions and purified on Sepharose CL-4B. The
      xylan structure was investigated by enzymatic hydrolysis with an endo-beta(1->4)
      xylanase followed by chromatography of the resulting fragments on Biogel P2,
      characterization by sugar analysis and matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS ). The results show
      that the A. spinosa xylan is composed of a beta-(1->4)-d-xylopyranose backbone
      substituted with 4-O-methyl-d-glucuronic acid and L-arabinose residues.

PMID- 27879640
TI  - New Homoisoflavanes, a New Alkaloid and Spirostane Steroids from the Roots of
      Herreria montevidensis Klotzsch ex Griseb. (Herreriaceae).
AB  - The roots of the South American vine Herreria montevidensis Klotzsch ex Griseb.
      (Herreriaceae) are used in traditional medicine by several Amerindian groups of
      the Paraguayan Chaco. Little is known on the chemistry of the plant, despite its
      widespread use across the South American Chaco. From the ethyl acetate/methanol
      1:1 extract of the roots, four new and one known homoisoflavanoid, two flavan
      derivatives, a stilbene, a new alkaloid, and three new and four known spirostane
      steroids were isolated. The corresponding structures were elucidated by
      spectroscopic and spectrometric means. The homoisoflavonoids of the plant are
      related to compounds isolated from the Dracaenaceae (formerly Agavaceae) sources
      of the Chinese crude drug Dragon's Blood. The new alkaloid is a novel skeleton
      that can be used as a chemical marker of Herreria. The spirostane steroids
      suggest chemotaxonomic relations with the Liliales. This is the first
      comprehensive report on the chemistry of a South American Herreria species.

PMID- 27879639
TI  - Disposable Amperometric Immunosensor for the Determination of Human P53 Protein
      in Cell Lysates Using Magnetic Micro-Carriers.
AB  - An amperometric magnetoimmunosensor for the determination of human p53 protein is
      described in this work using a sandwich configuration involving the covalent
      immobilization of a specific capture antibody onto activated carboxylic-modified
      magnetic beads (HOOC-MBs) and incubation of the modified MBs with a mixture of
      the target protein and horseradish peroxidase-labeled antibody (HRP-anti-p53).
      The resulting modified MBs are captured by a magnet placed under the surface of a
      disposable carbon screen-printed electrode (SPCE) and the amperometric responses
      are measured at -0.20 V (vs. an Ag pseudo-reference electrode), upon addition of
      hydroquinone (HQ) as a redox mediator and H2O2 as the enzyme substrate. The
      magnetoimmunosensing platform was successfully applied for the detection of p53
      protein in different cell lysates without any matrix effect after a simple sample
      dilution. The results correlated accurately with those provided by a commercial
      ELISA kit, thus confirming the immunosensor as an attractive alternative for
      rapid and simple determination of this protein using portable and affordable
      instrumentation.

PMID- 27879641
TI  - Hydrogen Induced Abrupt Structural Expansion at High Temperatures of a
      Ni32Nb28Zr30Cu10 Membrane for H2 Purification.
AB  - Ni-Nb-Zr amorphous membranes, prepared by melt-spinning, show great potential for
      replacing crystalline Pd-based materials in the field of hydrogen purification to
      an ultrapure grade (>99.999%). In this study, we investigate the temperature
      evolution of the structure of an amorphous ribbon with the composition
      Ni32Nb28Zr30Cu10 (expressed in atom %) by means of XRD and DTA measurements. An
      abrupt structural expansion is induced between 240 and 300  degrees C by
      hydrogenation. This structural modification deeply modifies the hydrogen sorption
      properties of the membrane, which indeed shows a strong reduction of the hydrogen
      capacity above 270  degrees C.

PMID- 27879643
TI  - Structures and Ribosomal Interaction of Ribosome-Inactivating Proteins.
AB  - Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and
      trichosanthin, are RNA N-glycosidases that depurinate a specific adenine residue
      (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved alpha-sarcin/ricin loop
      (alpha-SRL) of rRNA. RIPs are grouped into three types according to the number of
      subunits and the organization of the precursor sequences. RIPs are two-domain
      proteins, with the active site located in the cleft between the N- and C-terminal
      domains. It has been found that the basic surface residues of the RIPs promote
      rapid and specific targeting to the ribosome and a number of RIPs have been shown
      to interact with the C-terminal regions of the P proteins of the ribosome. At
      present, the structural basis for the interaction of trichosanthin and ricin-A
      chain toward P2 peptide is known. This review surveys the structural features of
      the representative RIPs and discusses how they approach and interact with the
      ribosome.

PMID- 27879642
TI  - Curcumin and Boswellia serrata Modulate the Glyco-Oxidative Status and Lipo
      Oxidation in Master Athletes.
AB  - BACKGROUND: Chronic intensive exercise is associated with a greater induction of
      oxidative stress and with an excess of endogenous advanced glycation end-products
      (AGEs). Curcumin can reduce the accumulation of AGEs in vitro and in animal
      models. We examined whether supplementation with curcumin and Boswellia serrata
      (BSE) gum resin for 3 months could affect plasma levels of markers of oxidative
      stress, inflammation, and glycation in healthy master cyclists. METHODS: Forty
      seven healthy male athletes were randomly assigned to Group 1, consisting of 22
      subjects given a Mediterranean diet (MD) alone (MD group), and Group 2 consisted
      of 25 subjects given a MD plus curcumin and BSE (curcumin/BSE group). Interleukin
      6 (IL-6), tumor necrosis factor-alpha (TNFalpha), high-sensitivity c-reactive
      protein (hs-CRP), total AGE, soluble receptor for AGE (sRAGE), malondialdehyde
      (MDA), plasma phospholipid fatty acid (PPFA) composition, and non-esterified
      fatty acids (NEFA) were tested at baseline and after 12 weeks. RESULTS: sRAGE,
      NEFA, and MDA decreased significantly in both groups, while only the curcumin/BSE
      group showed a significant decline in total AGE. Only the changes in total AGE
      and MDA differed significantly between the curcumin/BSE and MD groups.
      CONCLUSIONS: Our data suggest a positive effect of supplementation with curcumin
      and BSE on glycoxidation and lipid peroxidation in chronically exercising master
      athletes.

PMID- 27879644
TI  - Efficacy of Topical Application, Leaf Residue or Soil Drench of Blastospores of
      Isaria fumosorosea for Citrus Root Weevil Management: Laboratory and Greenhouse
      Investigations.
AB  - The efficacy of topical, leaf residue, and soil drench applications with Isaria
      fumosorosea blastospores (Ifr strain 3581) was assessed for the management of the
      citrus root weevil, Diaprepes abbreviatus (L.). Blastospores of Ifr were applied
      topically at a rate of 107 blastospores mL-1 on both the larvae and adults, and
      each insect stage was incubated in rearing cups with artificial diet at 25 
      degrees C, either in the dark or in a growth chamber under a 16 h photophase for
      2 weeks, respectively. Percent larval and adult mortality due to the infection of
      Ifr was assessed after 14 days as compared to untreated controls. Leaf residue
      assays were assessed by feeding the adults detached citrus leaves previously
      sprayed with Ifr (107 blastospores mL-1) in Petri dish chambers and then
      incubating them at 25  degrees C for 2-3 weeks. Efficacy of the soil drench
      applications was assessed on five larvae feeding on the roots of a Carrizo hybrid
      citrus seedling ~8.5-10.5 cm below the sterile sand surface in a single 16 cm *
      15.5 cm pot inside a second pot lined with plastic mesh to prevent escapees.
      Drench treatments per pot consisted of 100 mL of Ifr suspension (107 blastospores
      mL-1), flushed with 400, 900, or 1400 mL of water compared to 500, 1000, and 1500
      mL of water only for controls. The mean concentration of Ifr propagules as colony
      forming units per gram (CFUs g-1) that leached to different depths in the sand
      profile per treatment drench rate was also determined. Two weeks post-drenching
      of Ifr treatments, larvae were assessed for percent mortality, size differences,
      and effect of treatments in reducing feeding damage to the plant root biomass
      compared to the controls. Topical spray applications caused 13 and 19% mortality
      in larvae and adults after 7 days compared to none in the control after 14 days,
      respectively. Adults feeding on a single Ifr treated leaf for 24 h consumed less
      than the control, and resulted in 100% mortality 35 days post-treatment compared
      to 33% in the untreated control. Although offered fresh, untreated leaves after
      24 h, only adults in the control group consumed them. Ifr CFUs g-1 were isolated
      8.5-10.5 cm below the sand surface for the 1000 and 1500 mL drench rates only,
      resulting in 2%-4% larval mortality. For all the Ifr drench treatments, no
      differences were observed in percent larval mortality and size or the effect of
      treatments in reducing feeding damage to the plant root biomass compared to the
      controls. These results suggest that the foliar application of Ifr may be an
      efficient biocontrol strategy for managing adult populations of D. abbreviatus;
      potential alternative larval management strategies are discussed.

PMID- 27879645
TI  - Bio-Guided Isolation of Methanol-Soluble Metabolites of Common Spruce (Picea
      abies) Bark by-Products and Investigation of Their Dermo-Cosmetic Properties.
AB  - Common spruce (Picea abies L.) is a fast-growing coniferous tree, widely used in
      several countries for the production of sawn wood, timber and pulp. During this
      industrial exploitation, large quantities of barks are generated as waste
      materials. The aim of this study was the bio-guided investigation and the
      effective recovery of methanol-soluble metabolites of common spruce bark for the
      development of new dermo-cosmetic agents. The active methanol extract was
      initially fractionated by Centrifugal Partition Chromatography (CPC) using a
      triphasic solvent system in a step-gradient elution mode. All resulting fractions
      were evaluated for their antibacterial activity, antioxidant activity and their
      capability to inhibit tyrosinase, elastase and collagenase activity. In parallel,
      the chemical composition of each fraction was established by combining a 13C-NMR
      dereplication approach and 2D-NMR analyses. As a result, fourteen secondary
      metabolites corresponding to stilbene, flavonoid and phenolic acid derivatives
      were directly identified in the CPC fractions. A high amount (0.93 g) of E
      astringin was recovered from 3 g of crude extract in a single 125 min run. E
      Astringin significantly induced the tyrosinase activity while E-piceid,
      taxifolin, and taxifolin-3'-O-glucopyranoside exhibited significant anti
      tyrosinase activity. The above compounds showed important anti-collagenase and
      antimicrobial activities, thus providing new perspectives for potential
      applications as cosmetic ingredients.

PMID- 27879646
TI  - Integrating scFv into xMAP Assays for the Detection of Marine Toxins.
AB  - Marine toxins, such as saxitoxin and domoic acid are associated with algae blooms
      and can bioaccumulate in shell fish which present both health and economic
      concerns. The ability to detect the presence of toxin is paramount for the
      administration of the correct supportive care in case of intoxication;
      environmental monitoring to detect the presence of toxin is also important for
      prevention of intoxication. Immunoassays are one tool that has successfully been
      applied to the detection of marine toxins. Herein, we had the variable regions of
      two saxitoxin binding monoclonal antibodies sequenced and used the information to
      produce recombinant constructs that consist of linked heavy and light variable
      domains that make up the binding domains of the antibodies (scFv). Recombinantly
      produced binding elements such as scFv provide an alternative to traditional
      antibodies and serve to "preserve" monoclonal antibodies as they can be easily
      recreated from their sequence data. In this paper, we combined the anti-saxitoxin
      scFv developed here with a previously developed anti-domoic acid scFv and
      demonstrated their utility in a microsphere-based competitive immunoassay format.
      In addition to detection in buffer, we demonstrated equivalent sensitivity in
      oyster and scallop matrices. The potential for multiplexed detection using scFvs
      in this immunoassay format is demonstrated.

PMID- 27879649
TI  - Probabilistic Model Updating for Sizing of Hole-Edge Crack Using Fiber Bragg
      Grating Sensors and the High-Order Extended Finite Element Method.
AB  - This paper presents a novel framework for probabilistic crack size quantification
      using fiber Bragg grating (FBG) sensors. The key idea is to use a high-order
      extended finite element method (XFEM) together with a transfer (T)-matrix method
      to analyze the reflection intensity spectra of FBG sensors, for various crack
      sizes. Compared with the standard FEM, the XFEM offers two superior capabilities:
      (i) a more accurate representation of fields in the vicinity of the crack tip
      singularity and (ii) alleviation of the need for costly re-meshing as the crack
      size changes. Apart from the classical four-term asymptotic enrichment functions
      in XFEM, we also propose to incorporate higher-order functions, aiming to further
      improve the accuracy of strain fields upon which the reflection intensity spectra
      are based. The wavelength of the reflection intensity spectra is extracted as a
      damage sensitive quantity, and a baseline model with five parameters is
      established to quantify its correlation with the crack size. In order to test the
      feasibility of the predictive model, we design FBG sensor-based experiments to
      detect fatigue crack growth in structures. Furthermore, a Bayesian method is
      proposed to update the parameters of the baseline model using only a few
      available experimental data points (wavelength versus crack size) measured by one
      of the FBG sensors and an optical microscope, respectively. Given the remaining
      data points of wavelengths, even measured by FBG sensors at different positions,
      the updated model is shown to give crack size predictions that match well with
      the experimental observations.

PMID- 27879648
TI  - The Role of Deoxycytidine Kinase (dCK) in Radiation-Induced Cell Death.
AB  - Deoxycytidine kinase (dCK) is a key enzyme in deoxyribonucleoside salvage and the
      anti-tumor activity for many nucleoside analogs. dCK is activated in response to
      ionizing radiation (IR)-induced DNA damage and it is phosphorylated on Serine 74
      by the Ataxia-Telangiectasia Mutated (ATM) kinase in order to activate the cell
      cycle G2/M checkpoint. However, whether dCK plays a role in radiation-induced
      cell death is less clear. In this study, we genetically modified dCK expression
      by knocking down or expressing a WT (wild-type), S74A (abrogates phosphorylation)
      and S74E (mimics phosphorylation) of dCK. We found that dCK could decrease IR
      induced total cell death and apoptosis. Moreover, dCK increased IR-induced
      autophagy and dCK-S74 is required for it. Western blotting showed that the ratio
      of phospho-Akt/Akt, phospho-mTOR/mTOR, phospho-P70S6K/P70S6K significantly
      decreased in dCK-WT and dCK-S74E cells than that in dCK-S74A cells following IR
      treatment. Reciprocal experiment by co-immunoprecipitation showed that mTOR can
      interact with wild-type dCK. IR increased polyploidy and decreased G2/M arrest in
      dCK knock-down cells as compared with control cells. Taken together,
      phosphorylated and activated dCK can inhibit IR-induced cell death including
      apoptosis and mitotic catastrophe, and promote IR-induced autophagy through
      PI3K/Akt/mTOR pathway.

PMID- 27879647
TI  - Neuroprotective Strategies during Cardiac Surgery with Cardiopulmonary Bypass.
AB  - Aortocoronary bypass or valve surgery usually require cardiac arrest using
      cardioplegic solutions. Although, in principle, in a number of cases beating
      heart surgery (so-called off-pump technique) is possible, aortic or valve surgery
      or correction of congenital heart diseases mostly require cardiopulmonary arrest.
      During this condition, the heart-lung machine also named cardiopulmonary bypass
      (CPB) has to take over the circulation. It is noteworthy that the invention of a
      machine bypassing the heart and lungs enabled complex cardiac operations, but
      possible negative effects of the CPB on other organs, especially the brain,
      cannot be neglected. Thus, neuroprotection during CPB is still a matter of great
      interest. In this review, we will describe the impact of CPB on the brain and
      focus on pharmacological and non-pharmacological strategies to protect the brain.

PMID- 27879650
TI  - Posttraumatic Stress Disorder: Overview of Evidence-Based Assessment and
      Treatment.
AB  - Posttraumatic stress disorder (PTSD) is a chronic psychological disorder that can
      develop after exposure to a traumatic event. This review summarizes the
      literature on the epidemiology, assessment, and treatment of PTSD. We provide a
      review of the characteristics of PTSD along with associated risk factors, and
      describe brief, evidence-based measures that can be used to screen for PTSD and
      monitor symptom changes over time. In regard to treatment, we highlight commonly
      used, evidence-based psychotherapies and pharmacotherapies for PTSD. Among
      psychotherapeutic approaches, evidence-based approaches include cognitive
      behavioral therapies (e.g., Prolonged Exposure and Cognitive Processing Therapy)
      and Eye Movement Desensitization and Reprocessing. A wide variety of
      pharmacotherapies have received some level of research support for PTSD symptom
      alleviation, although selective serotonin reuptake inhibitors have the largest
      evidence base to date. However, relapse may occur after the discontinuation of
      pharmacotherapy, whereas PTSD symptoms typically remain stable or continue to
      improve after completion of evidence-based psychotherapy. After reviewing
      treatment recommendations, we conclude by describing critical areas for future
      research.

PMID- 27879652
TI  - Fluid Intake of Pregnant and Breastfeeding Women in Indonesia: A Cross-Sectional
      Survey with a Seven-Day Fluid Specific Record.
AB  - During pregnancy and lactation, the adequate intake (AI) for total water intake
      is increased. This cross-sectional survey aimed to assess Total Fluid Intake
      (TFI; sum of drinking water and all other fluids) of 300 pregnant and 300
      breastfeeding women in Indonesia. A seven-day fluid specific record was used to
      assess TFI. Mean TFI of pregnant and breastfeeding women were 2332 +/- 746 mL/day
      and 2525 +/- 843 mL/day, respectively. No significant difference in TFI between
      pregnancy trimesters was observed, while TFI of women breastfeeding for 12-24
      months postpartum (2427 +/- 955 mL/day) was lower than that of the two other
      groups (0-5 months: 2607 +/- 754 mL/day; 6-11 months: 2538 +/- 807 mL/day,
      respectively). Forty-two and 54% of the pregnant and breastfeeding subjects,
      respectively, did not reach the AI of water from fluids. These AI were actually
      known by only 14% and 23% of the pregnant and breastfeeding subjects. However,
      having the knowledge about the AI did not increase the odds of reaching the AI.
      Concluding that a high proportion of the pregnant and breastfeeding subjects did
      not reach the AI of water from fluid, it seems pertinent to further assess the
      fluid intake, as well as their hydration status, in other countries.

PMID- 27879651
TI  - Prediction of Protein-Protein Interactions by Evidence Combining Methods.
AB  - Most cellular functions involve proteins' features based on their physical
      interactions with other partner proteins. Sketching a map of protein-protein
      interactions (PPIs) is therefore an important inception step towards
      understanding the basics of cell functions. Several experimental techniques
      operating in vivo or in vitro have made significant contributions to screening a
      large number of protein interaction partners, especially high-throughput
      experimental methods. However, computational approaches for PPI predication
      supported by rapid accumulation of data generated from experimental techniques,
      3D structure definitions, and genome sequencing have boosted the map sketching of
      PPIs. In this review, we shed light on in silico PPI prediction methods that
      integrate evidence from multiple sources, including evolutionary relationship,
      function annotation, sequence/structure features, network topology and text
      mining. These methods are developed for integration of multi-dimensional
      evidence, for designing the strategies to predict novel interactions, and for
      making the results consistent with the increase of prediction coverage and
      accuracy.

PMID- 27879653
TI  - Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth.
AB  - Ellagic acid (EA) is a polyphenolic compound that can be found as a naturally
      occurring hydrolysis product of ellagitannins in pomegranates, berries, grapes,
      green tea and nuts. Previous studies have reported the antitumor properties of EA
      mainly using in vitro models. No data are available about EA influence on bladder
      cancer cell invasion of the extracellular matrix triggered by vascular
      endothelial growth factor-A (VEGF-A), an angiogenic factor associated with
      disease progression and recurrence, and tumor growth in vivo. In this study, we
      have investigated EA activity against four different human bladder cancer cell
      lines (i.e., T24, UM-UC-3, 5637 and HT-1376) by in vitro proliferation tests
      (measuring metabolic and foci forming activity), invasion and chemotactic assays
      in response to VEGF-A and in vivo preclinical models in nude mice. Results
      indicate that EA exerts anti-proliferative effects as a single agent and enhances
      the antitumor activity of mitomycin C, which is commonly used for the treatment
      of bladder cancer. EA also inhibits tumor invasion and chemotaxis, specifically
      induced by VEGF-A, and reduces VEGFR-2 expression. Moreover, EA down-regulates
      the expression of programmed cell death ligand 1 (PD-L1), an immune checkpoint
      involved in immune escape. EA in vitro activity was confirmed by the results of
      in vivo studies showing a significant reduction of the growth rate, infiltrative
      behavior and tumor-associated angiogenesis of human bladder cancer xenografts. In
      conclusion, these results suggest that EA may have a potential role as an adjunct
      therapy for bladder cancer.

PMID- 27879655
TI  - Phomopsichin A-D; Four New Chromone Derivatives from Mangrove Endophytic Fungus
      Phomopsis sp. 33.
AB  - Four new chromone derivatives, phomopsichins A-D (1-4), along with a known
      compound, phomoxanthone A (5), were isolated from the fermentation products of
      mangrove endophytic fungus Phomopsis sp. 33#. Their structures were elucidated
      based on comprehensive spectroscopic analysis coupled with single-crystal X-ray
      diffraction or theoretical calculations of electronic circular dichroism (ECD).
      They feature a tricyclic framework, in which a dihydropyran ring is fused with
      the chromone ring. Compounds 1-5 showed weak inhibitory activities on
      acetylcholinesterase as well as alpha-glucosidase, weak radical scavenging
      effects on 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as OH, and weak
      antimicrobial activities. Compounds 1-4 showed no cytotoxic activity against MDA
      MB-435 breast cancer cells. Their other bioactivities are worthy of further
      study, considering their unique molecular structures.

PMID- 27879654
TI  - Early Antipsychotic Treatment in Juvenile Rats Elicits Long-Term Alterations to
      the Dopamine Neurotransmitter System.
AB  - Prescription of antipsychotic drugs (APDs) to children has substantially
      increased in recent years. Whilst current investigations into potential long-term
      effects have uncovered some alterations to adult behaviours, further
      investigations into potential changes to neurotransmitter systems are required.
      The current study investigated potential long-term changes to the adult dopamine
      (DA) system following aripiprazole, olanzapine and risperidone treatment in
      female and male juvenile rats. Levels of tyrosine hydroxylase (TH),
      phosphorylated-TH (p-TH), dopamine active transporter (DAT), and D1 and D2
      receptors were measured via Western blot and/or receptor autoradiography.
      Aripiprazole decreased TH and D1 receptor levels in the ventral tegmental area
      (VTA) and p-TH levels in the prefrontal cortex (PFC) of females, whilst TH levels
      decreased in the PFC of males. Olanzapine decreased PFC p-TH levels and increased
      D2 receptor expression in the PFC and nucleus accumbens (NAc) in females only.
      Additionally, risperidone treatment increased D1 receptor levels in the
      hippocampus of females, whilst, in males, p-TH levels increased in the PFC and
      hippocampus, D1 receptor expression decreased in the NAc, and DAT levels
      decreased in the caudate putamen (CPu), and elevated in the VTA. These results
      suggest that early treatment with various APDs can cause different long-term
      alterations in the adult brain, across both treatment groups and genders.

PMID- 27879657
TI  - Screening for Mutations in the TBX1 Gene on Chromosome 22q11.2 in Schizophrenia.
AB  - A higher-than-expected frequency of schizophrenia in patients with 22q11.2
      deletion syndrome suggests that chromosome 22q11.2 harbors the responsive genes
      related to the pathophysiology of schizophrenia. The TBX1 gene, which maps to the
      region on chromosome 22q11.2, plays a vital role in neuronal functions.
      Haploinsufficiency of the TBX1 gene is associated with schizophrenia
      endophenotype. This study aimed to investigate whether the TBX1 gene is
      associated with schizophrenia. We searched for mutations in the TBX1 gene in 652
      patients with schizophrenia and 567 control subjects using a re-sequencing method
      and conducted a reporter gene assay. We identified six SNPs and 25 rare mutations
      with no association with schizophrenia from Taiwan. Notably, we identified two
      rare schizophrenia-specific mutations (c.-123G>C and c.-11delC) located at 5' UTR
      of the TBX1 gene. The reporter gene assay showed that c.-123C significantly
      decreased promoter activity, while c.-11delC increased promoter activity compared
      with the wild-type. Our findings suggest that the TBX1 gene is unlikely a major
      susceptible gene for schizophrenia in an ethnic Chinese population for Taiwan,
      but a few rare mutations in the TBX1 gene may contribute to the pathogenesis of
      schizophrenia in some patients.

PMID- 27879656
TI  - Fish Consumption and Age-Related Macular Degeneration Incidence: A Meta-Analysis
      and Systematic Review of Prospective Cohort Studies.
AB  - The association between fish consumption and risk of age-related macular
      degeneration (AMD) is still unclear. The aim of the current meta-analysis and
      systematic review was to quantitatively evaluate findings from observational
      studies on fish consumption and the risk of AMD. Relevant studies were identified
      by searching electronic databases (Medline and EMBASE) and reviewing the
      reference lists of relevant articles up to August, 2016. Prospective cohort
      studies that reported relative risks (RRs) and 95% confidence intervals (CIs) for
      the link between fish consumption and risk of AMD were included. A total of 4202
      cases with 128,988 individuals from eight cohort studies were identified in the
      current meta-analysis. The meta-analyzed RR was 0.76 (95% CI, 0.65-0.90) when any
      AMD was considered. Subgroup analyses by AMD stages showed that fish consumption
      would reduce the risk of both early (RR, 0.83; 95% CI, 0.72-0.96) and late (RR;
      0.76; 95% CI, 0.60-0.97) AMD. When stratified by the follow-up duration, fish
      consumption was a protective factor of AMD in both over 10 years (n = 5; RR,
      0.81; 95% CI, 0.67-0.97) and less than 10 years (n = 3; RR, 0.70; 95% CI, 0.51 to
      0.97) follow-up duration. Stratified analyses by fish type demonstrated that dark
      meat fish (RR, 0.68, 95% CI, 0.46-0.99), especially tuna fish (RR, 0.58; 95% CI,
      95% CI, 0.47-0.71) intake was associated with reduced AMD risk. Evidence of a
      linear association between dose of fish consumption and risk of AMD was
      demonstrated. The results of this meta-analysis demonstrated that fish
      consumption can reduce AMD risk. Advanced, well-designed, randomized clinical
      trials are required in order to validate the conclusions in this study.

PMID- 27879659
TI  - Innovative Alternative Technologies to Extract Carotenoids from Microalgae and
      Seaweeds.
AB  - Marine microalgae and seaweeds (microalgae) represent a sustainable source of
      various bioactive natural carotenoids, including beta-carotene, lutein,
      astaxanthin, zeaxanthin, violaxanthin and fucoxanthin. Recently, the large-scale
      production of carotenoids from algal sources has gained significant interest with
      respect to commercial and industrial applications for health, nutrition, and
      cosmetic applications. Although conventional processing technologies, based on
      solvent extraction, offer a simple approach to isolating carotenoids, they suffer
      several, inherent limitations, including low efficiency (extraction yield),
      selectivity (purity), high solvent consumption, and long treatment times, which
      have led to advancements in the search for innovative extraction technologies.
      This comprehensive review summarizes the recent trends in the extraction of
      carotenoids from microalgae and seaweeds through the assistance of different
      innovative techniques, such as pulsed electric fields, liquid pressurization,
      supercritical fluids, subcritical fluids, microwaves, ultrasounds, and high
      pressure homogenization. In particular, the review critically analyzes
      technologies, characteristics, advantages, and shortcomings of the different
      innovative processes, highlighting the differences in terms of yield,
      selectivity, and economic and environmental sustainability.

PMID- 27879661
TI  - Bamboo Classification Using WorldView-2 Imagery of Giant Panda Habitat in a Large
      Shaded Area in Wolong, Sichuan Province, China.
AB  - This study explores the ability of WorldView-2 (WV-2) imagery for bamboo mapping
      in a mountainous region in Sichuan Province, China. A large area of this place is
      covered by shadows in the image, and only a few sampled points derived were
      useful. In order to identify bamboos based on sparse training data, the sample
      size was expanded according to the reflectance of multispectral bands selected
      using the principal component analysis (PCA). Then, class separability based on
      the training data was calculated using a feature space optimization method to
      select the features for classification. Four regular object-based classification
      methods were applied based on both sets of training data. The results show that
      the k-nearest neighbor (k-NN) method produced the greatest accuracy. A
      geostatistically-weighted k-NN classifier, accounting for the spatial correlation
      between classes, was then applied to further increase the accuracy. It achieved
      82.65% and 93.10% of the producer's and user's accuracies respectively for the
      bamboo class. The canopy densities were estimated to explain the result. This
      study demonstrates that the WV-2 image can be used to identify small patches of
      understory bamboos given limited known samples, and the resulting bamboo
      distribution facilitates the assessments of the habitats of giant pandas.

PMID- 27879658
TI  - The Emergence of Pan-Cancer CIMP and Its Elusive Interpretation.
AB  - Epigenetic dysregulation is recognized as a hallmark of cancer. In the last 16
      years, a CpG island methylator phenotype (CIMP) has been documented in tumors
      originating from different tissues. However, a looming question in the field is
      whether or not CIMP is a pan-cancer phenomenon or a tissue-specific event. Here,
      we give a synopsis of the history of CIMP and describe the pattern of DNA
      methylation that defines the CIMP phenotype in different cancer types. We
      highlight new conceptual approaches of classifying tumors based on CIMP in a
      cancer type-agnostic way that reveal the presence of distinct CIMP tumors in a
      multitude of The Cancer Genome Atlas (TCGA) datasets, suggesting that this
      phenotype may transcend tissue-type specificity. Lastly, we show evidence
      supporting the clinical relevance of CIMP-positive tumors and suggest that a
      common CIMP etiology may define new mechanistic targets in cancer treatment.

PMID- 27879663
TI  - Queuing Time Prediction Using WiFi Positioning Data in an Indoor Scenario.
AB  - Queuing is common in urban public places. Automatically monitoring and predicting
      queuing time can not only help individuals to reduce their wait time and
      alleviate anxiety but also help managers to allocate resources more efficiently
      and enhance their ability to address emergencies. This paper proposes a novel
      method to estimate and predict queuing time in indoor environments based on WiFi
      positioning data. First, we use a series of parameters to identify the
      trajectories that can be used as representatives of queuing time. Next, we divide
      the day into equal time slices and estimate individuals' average queuing time
      during specific time slices. Finally, we build a nonstandard autoregressive (NAR)
      model trained using the previous day's WiFi estimation results and actual queuing
      time to predict the queuing time in the upcoming time slice. A case study
      comparing two other time series analysis models shows that the NAR model has
      better precision. Random topological errors caused by the drift phenomenon of
      WiFi positioning technology (locations determined by a WiFi positioning system
      may drift accidently) and systematic topological errors caused by the positioning
      system are the main factors that affect the estimation precision. Therefore, we
      optimize the deployment strategy during the positioning system deployment phase
      and propose a drift ratio parameter pertaining to the trajectory screening phase
      to alleviate the impact of topological errors and improve estimates. The WiFi
      positioning data from an eight-day case study conducted at the T3-C entrance of
      Beijing Capital International Airport show that the mean absolute estimation
      error is 147 s, which is approximately 26.92% of the actual queuing time. For
      predictions using the NAR model, the proportion is approximately 27.49%. The
      theoretical predictions and the empirical case study indicate that the NAR model
      is an effective method to estimate and predict queuing time in indoor public
      areas.

PMID- 27879660
TI  - Gold Nanoparticles for Diagnostics: Advances towards Points of Care.
AB  - The remarkable physicochemical properties of gold nanoparticles (AuNPs) have
      prompted developments in the exploration of biomolecular interactions with AuNP
      containing systems, in particular for biomedical applications in diagnostics.
      These systems show great promise in improving sensitivity, ease of operation and
      portability. Despite this endeavor, most platforms have yet to reach maturity and
      make their way into clinics or points of care (POC). Here, we present an overview
      of emerging and available molecular diagnostics using AuNPs for biomedical
      sensing that are currently being translated to the clinical setting.

PMID- 27879662
TI  - Retinol Dehydrogenases Regulate Vitamin A Metabolism for Visual Function.
AB  - The visual system produces visual chromophore, 11-cis-retinal from dietary
      vitamin A, all-trans-retinol making this vitamin essential for retinal health and
      function. These metabolic events are mediated by a sequential biochemical process
      called the visual cycle. Retinol dehydrogenases (RDHs) are responsible for two
      reactions in the visual cycle performed in retinal pigmented epithelial (RPE)
      cells, photoreceptor cells and Muller cells in the retina. RDHs in the RPE
      function as 11-cis-RDHs, which oxidize 11-cis-retinol to 11-cis-retinal in vivo.
      RDHs in rod photoreceptor cells in the retina work as all-trans-RDHs, which
      reduce all-trans-retinal to all-trans-retinol. Dysfunction of RDHs can cause
      inherited retinal diseases in humans. To facilitate further understanding of
      human diseases, mouse models of RDHs-related diseases have been carefully
      examined and have revealed the physiological contribution of specific RDHs to
      visual cycle function and overall retinal health. Herein we describe the function
      of RDHs in the RPE and the retina, particularly in rod photoreceptor cells, their
      regulatory properties for retinoid homeostasis and future therapeutic strategy
      for treatment of retinal diseases.

PMID- 27879666
TI  - Structural Analysis of Sortase A Inhibitors.
AB  - Bacterial sortases are cysteine transpeptidases that regulate the covalent
      linkage of several surface protein virulence factors in Gram-positive bacteria.
      Virulence factors play significant roles in adhesion, invasion of host tissues,
      biofilm formation and immune evasion, mediating the bacterial pathogenesis and
      infectivity. Therefore, sortases are emerging as important targets for the design
      of new anti-infective agents. We employed a computational study, based on
      structure derived descriptors and molecular fingerprints, in order to develop
      simple classification methods which could allow predicting low active or high
      active SrtA inhibitors. Our results indicate that a highly active SrtA inhibitor
      has a molecular weight ranging between 180 and 600, contains one up to four
      nitrogen atoms, up to three oxygen atoms and under 18 hydrogen atoms. Also the
      hydrogen acceptor number and the molecular flexibility, as assessed by the number
      of rotatable bounds, have emerged as the most relevant descriptors for SrtA
      affinity. The Bemis-Murcko scaffolding revealed favoured scaffolds as containing
      at least two ring structures bonded directly or merged in a condensed cycle. This
      data represent a valuable tool for identifying new potent SrtA inhibitors,
      potential anti-virulence agents targeted against Gram-positive bacteria,
      including multiresistant strains.

PMID- 27879665
TI  - Effects of Luteolin and Quercetin in Combination with Some Conventional
      Antibiotics against Methicillin-Resistant Staphylococcus aureus.
AB  - The present study was designed to evaluate the effects of flavonoids luteolin (L)
      and quercetin + luteolin (Q + L) in combination with commonly used antibacterial
      agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical
      isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of
      L and Q + L, as well as the MICs of flavonoids in combination with antibiotics
      were determined and results showed an increased activity of flavonoids with
      antibiotics. The synergistic, additive, or antagonistic relationships between
      flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and
      synergistic effects were observed for some antibiotic + flavonoid combinations.
      In addition, some combinations were also found to damage the bacterial
      cytoplasmic membrane, as assessed through potassium leakage assay. The effects of
      flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested,
      and no functional variation was detected in the coding region.

PMID- 27879664
TI  - Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7
      Cells.
AB  - Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from
      the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy
      for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have
      not been fully elucidated. In this study, we investigated the molecular
      mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated
      RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and
      pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in RAW264.7 cells stimulated
      with LPS. A reverse-transcription polymerase chain reaction assay and Western
      blot further confirmed that CTB inhibited the expression of inducible nitric
      oxide synthase, cyclooxygenase-2, TNF-alpha, and IL-1beta at the transcriptional
      level, and decreased the luciferase activities of activator protein (AP)-1
      reporter promoters. These data suggest that inhibition occurred at the
      transcriptional level. In addition, CTB blocked the activation of p38 mitogen
      activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular
      signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of
      MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our
      findings clearly show that CTB inhibits the production of inflammatory mediators
      by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be
      used as an anti-inflammatory agent.

PMID- 27879668
TI  - Structure-Functional Basis of Ion Transport in Sodium-Calcium Exchanger (NCX)
      Proteins.
AB  - The membrane-bound sodium-calcium exchanger (NCX) proteins shape Ca2+ homeostasis
      in many cell types, thus participating in a wide range of physiological and
      pathological processes. Determination of the crystal structure of an archaeal NCX
      (NCX_Mj) paved the way for a thorough and systematic investigation of ion
      transport mechanisms in NCX proteins. Here, we review the data gathered from the
      X-ray crystallography, molecular dynamics simulations, hydrogen-deuterium
      exchange mass-spectrometry (HDX-MS), and ion-flux analyses of mutants.
      Strikingly, the apo NCX_Mj protein exhibits characteristic patterns in the local
      backbone dynamics at particular helix segments, thereby possessing characteristic
      HDX profiles, suggesting structure-dynamic preorganization (geometric
      arrangements of catalytic residues before the transition state) of conserved
      alpha1 and alpha2 repeats at ion-coordinating residues involved in transport
      activities. Moreover, dynamic preorganization of local structural entities in the
      apo protein predefines the status of ion-occlusion and transition states, even
      though Na+ or Ca2+ binding modifies the preceding backbone dynamics nearby
      functionally important residues. Future challenges include resolving the
      structural-dynamic determinants governing the ion selectivity, functional
      asymmetry and ion-induced alternating access. Taking into account the structural
      similarities of NCX_Mj with the other proteins belonging to the Ca2+/cation
      exchanger superfamily, the recent findings can significantly improve our
      understanding of ion transport mechanisms in NCX and similar proteins.

PMID- 27879669
TI  - Synthesis of a Morpholino Nucleic Acid (MNA)-Uridine Phosphoramidite, and Exon
      Skipping Using MNA/2'-O-Methyl Mixmer Antisense Oligonucleotide.
AB  - In this study, we synthesised a morpholino nucleoside-uridine (MNA-U)
      phosphoramidite and evaluated the potential of a MNA-modified antisense
      oligonucleotide (AO) sequences to induce exon 23 skipping in mdx mouse myotubes
      in vitro towards extending the applicability of morpholino chemistry with other
      nucleotide monomers. We designed, synthesised, and compared exon skipping
      efficiencies of 20 mer MNA-modified 2'-O-methyl RNA mixmer AO on a
      phosphorothioate backbone (MNA/2'-OMePS) to the corresponding fully modified 2'-O
      methyl RNA AO (2'-OMePS) as a control. Our results showed that the MNA/2'-OMePS
      efficiently induced exon 23 skipping. As expected, the 2'-OMePS AO control
      yielded efficient exon 23 skipping. Under the applied conditions, both the AOs
      showed minor products corresponding to exon 22/23 dual exon skipping in low
      yield. As these are very preliminary data, more detailed studies are necessary;
      however, based on the preliminary results, MNA nucleotides might be useful in
      constructing antisense oligonucleotides.

PMID- 27879667
TI  - Biological Chemistry of Hydrogen Selenide.
AB  - There are no two main-group elements that exhibit more similar physical and
      chemical properties than sulfur and selenium. Nonetheless, Nature has deemed both
      essential for life and has found a way to exploit the subtle unique properties of
      selenium to include it in biochemistry despite its congener sulfur being 10,000
      times more abundant. Selenium is more easily oxidized and it is kinetically more
      labile, so all selenium compounds could be considered to be "Reactive Selenium
      Compounds" relative to their sulfur analogues. What is furthermore remarkable is
      that one of the most reactive forms of selenium, hydrogen selenide (HSe- at
      physiologic pH), is proposed to be the starting point for the biosynthesis of
      selenium-containing molecules. This review contrasts the chemical properties of
      sulfur and selenium and critically assesses the role of hydrogen selenide in
      biological chemistry.

PMID- 27879670
TI  - The Protective Effects of Icariin against the Homocysteine-Induced Neurotoxicity
      in the Primary Embryonic Cultures of Rat Cortical Neurons.
AB  - Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM),
      has been considered as a potential therapeutic agent for neurodegenerative
      diseases such as Alzheimer's disease (AD). Hyperhomocysteinaemia is a risk factor
      for AD and other associated neurological diseases. In this study we aim to
      investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity
      in primary embryonic cultures of rat cortical neurons. Our findings demonstrated
      that icariin might be able restore the cytoskeleton network damaged by Hcy
      through the modulation of acetyl-alpha-tubulin, tyrosinated-alpha-tubulin, and
      phosphorylation of the tubulin-binding protein Tau. In addition, icariin
      downregulated p-extracellular signal-regulated kinase (ERK) which is a kinase
      targeting tau protein. Furthermore, icariin effectively restored the
      neuroprotective protein p-Akt that was downregulated by Hcy. We also applied RT2
      Profiler PCR Arrays focused on genes related to AD and neurotoxicity to examine
      genes differentially altered by Hcy or icariin. Among the altered genes from the
      arrays, ADAM9 was downregulated 15 folds in cells treated with Hcy, but markedly
      restored by icariin. ADAM family, encoded alpha-secreatase, plays a protective
      role in AD. Overall, our findings demonstrated that icariin exhibits a strong
      neuroprotective function and have potential for future development for drug
      treating neurological disorders, such as AD.

PMID- 27879671
TI  - A Comparative Study of Enantioseparations of Nalpha-Fmoc Proteinogenic Amino
      Acids on Quinine-Based Zwitterionic and Anion Exchanger-Type Chiral Stationary
      Phases under Hydro-Organic Liquid and Subcritical Fluid Chromatographic
      Conditions.
AB  - The focus of this contribution is a comparative investigation of
      enantioseparations of 19 Nalpha-Fmoc proteinogenic amino acids on Quinine-based
      zwitterionic and anion-exchanger type chiral stationary phases employing hydro
      organic and polar-ionic liquid and subcritical fluid chromatographic conditions.
      Effects of mobile phase composition (including additives, e.g., water, basis and
      acids) and nature of chiral selectors on the chromatographic performances were
      studied at different chromatographic modes. Thermodynamic parameters of the
      temperature dependent enantioseparation results were calculated in the
      temperature range 5-50  degrees C applying plots of lnalpha versus 1/T. The
      differences in standard enthalpy and standard entropy for a given pair of
      enantiomers were calculated and served as a basis for comparisons. Elution
      sequence in all cases was determined, where a general rule could be observed,
      both in liquid and subcritical fluid chromatographic mode the d-enantiomers
      eluted before the L ones. In both modes, the principles of ion exchange
      chromatography apply.

PMID- 27879673
TI  - 4-Hydroxyisoleucine from Fenugreek (Trigonella foenum-graecum): Effects on
      Insulin Resistance Associated with Obesity.
AB  - Obesity and insulin resistance (IR) are interdependent multifactorial processes
      that cannot be understood separately. Obesity leads to systemic inflammation and
      increased levels of free fatty acids that provoke IR and lipotoxicity. At the
      same time, IR exacerbates adipose cell dysfunction, resulting in chronic
      inflammation and major lipotoxic effects on nonadipose tissues. 4
      Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from
      fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR
      related to obesity. 4-OHIle increases glucose-induced insulin release, and the
      insulin response mediated by 4-OHIle depends on glucose concentration. The
      beneficial effects observed are related to the regulation of blood glucose,
      plasma triglycerides, total cholesterol, free fatty acid levels, and the
      improvement of liver function. The mechanism of action is related to increased
      Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2,
      extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein
      kinase (MAPK), and nuclear factor (NF)-kappaB. Here, we present a review of the
      research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle
      in in vitro and in vivo models.

PMID- 27879672
TI  - Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor
      Cells (OPCs) via beta1 Integrin.
AB  - The guided migration of neural cells is essential for repair in the central
      nervous system (CNS). Oligodendrocyte progenitor cells (OPCs) will normally
      migrate towards an injury site to re-sheath demyelinated axons; however the
      mechanisms underlying this process are not well understood. Endogenous electric
      fields (EFs) are known to influence cell migration in vivo, and have been
      utilised in this study to direct the migration of OPCs isolated from neonatal
      Sprague-Dawley rats. The OPCs were exposed to physiological levels of electrical
      stimulation, and displayed a marked electrotactic response that was dependent on
      beta1 integrin, one of the key subunits of integrin receptors. We also observed
      that F-actin, an important component of the cytoskeleton, was re-distributed
      towards the leading edge of the migrating cells, and that this asymmetric
      rearrangement was associated with beta1 integrin function.

PMID- 27879675
TI  - Evaluation of Hyaluronic Acid Dilutions at Different Concentrations Using a
      Quartz Crystal Resonator (QCR) for the Potential Diagnosis of Arthritic Diseases.
AB  - The main objective of this article is to demonstrate through experimental means
      the capacity of the quartz crystal resonator (QCR) to characterize biological
      samples of aqueous dilutions of hyaluronic acid according to their viscosity and
      how this capacity may be useful in the potential diagnosis of arthritic diseases.
      The synovial fluid is viscous due to the presence of hyaluronic acid, synthesized
      by synovial lining cells (type B), and secreted into the synovial fluid thus
      making the fluid viscous. In consequence, aqueous dilutions of hyaluronic acid
      may be used as samples to emulate the synovial fluid. Due to the viscoelastic and
      pseudo-plastic behavior of hyaluronic acid, it is necessary to use the Rouse
      model in order to obtain viscosity values comparable with viscometer measures. A
      Fungilab viscometer (rheometer) was used to obtain reference measures of the
      viscosity in each sample in order to compare them with the QCR prototype
      measures.

PMID- 27879674
TI  - Transcriptome Analysis of mRNA and miRNA in Somatic Embryos of Larix leptolepis
      Subjected to Hydrogen Treatment.
AB  - Hydrogen is a therapeutic antioxidant that has been used extensively in clinical
      trials. It also acts as a bioactive molecule that can alleviate abiotic stress in
      plants. However, the biological effects of hydrogen in somatic embryos and the
      underlying molecular basis remain largely unknown. In this study, the
      morphological and physiological influence of exogenous H2 treatment during
      somatic embryogenesis was characterized in Larix leptolepis Gordon. The results
      showed that exposure to hydrogen increased the proportions of active pro
      embryogenic cells and normal somatic embryos. We sequenced mRNA and microRNA
      (miRNA) libraries to identify global transcriptome changes at different time
      points during H2 treatment of larch pro-embryogenic masses (PEMs). A total of
      45,393 mRNAs and 315 miRNAs were obtained. Among them, 4253 genes and 96 miRNAs
      were differentially expressed in the hydrogen-treated libraries compared with the
      control. Further, a large number of the differentially expressed mRNAs and miRNAs
      were related to reactive oxygen species (ROS) homeostasis and cell cycle
      regulation. We also identified 4399 potential target genes for 285 of the miRNAs.
      The differential expression data and the mRNA-miRNA interaction network described
      here provide new insights into the molecular mechanisms that determine the
      performance of PEMs exposed to H2 during somatic embryogenesis.

PMID- 27879677
TI  - Pulmonary Function and Incidence of Selected Respiratory Diseases Depending on
      the Exposure to Ambient PM10.
AB  - It is essential in pulmonary disease research to take into account traffic
      related air pollutant exposure among urban inhabitants. In our study, 4985 people
      were examined for spirometric parameters in the presented research which was
      conducted in the years 2008-2012. The research group was divided into urban and
      rural residents. Traffic density, traffic structure and velocity, as well as
      concentrations of selected air pollutants (CO, NO2 and PM10) were measured at
      selected areas. Among people who live in the city, lower percentages of predicted
      values of spirometric parameters were noticed in comparison to residents of rural
      areas. Taking into account that the difference in the five-year mean
      concentration of PM10 in the considered city and rural areas was over 17 MUg/m3,
      each increase of PM10 by 10 MUg/m3 is associated with the decline in FEV1 (forced
      expiratory volume during the first second of expiration) by 1.68%. These findings
      demonstrate that traffic-related air pollutants may have a significant influence
      on the decline of pulmonary function and the growing rate of respiratory
      diseases.

PMID- 27879678
TI  - New Thiazolyl-triazole Schiff Bases: Synthesis and Evaluation of the Anti-Candida
      Potential.
AB  - In the context of the dangerous phenomenon of fungal resistance to the available
      therapies, we present here the chemical synthesis of a new series of thiazolyl
      triazole Schiff bases B1-B15, which were in vitro assessed for their anti-Candida
      potential. Compound B10 was found to be more potent against Candida spp. when
      compared with the reference drugs Fluconazole and Ketoconazole. A docking study
      of the newly synthesized Schiff bases was performed, and results showed good
      binding affinity in the active site of co-crystallized Itraconazole-lanosterol
      14alpha-demethylase isolated from Saccharomyces cerevisiae. An in silico ADMET
      (absorption, distribution, metabolism, excretion, toxicity) study was done in
      order to predict some pharmacokinetic and pharmacotoxicological properties. The
      Schiff bases showed good drug-like properties. The results of in vitro anti
      Candida activity, a docking study and ADMET prediction revealed that the newly
      synthesized compounds have potential anti-Candida activity and evidenced the most
      active derivative, B10, which can be further optimized as a lead compound.

PMID- 27879676
TI  - Calcium Dyshomeostasis in Tubular Aggregate Myopathy.
AB  - Calcium is a crucial mediator of cell signaling in skeletal muscles for basic
      cellular functions and specific functions, including contraction, fiber-type
      differentiation and energy production. The sarcoplasmic reticulum (SR) is an
      organelle that provides a large supply of intracellular Ca2+ in myofibers. Upon
      excitation, it releases Ca2+ into the cytosol, inducing contraction of
      myofibrils. During relaxation, it takes up cytosolic Ca2+ to terminate the
      contraction. During exercise, Ca2+ is cycled between the cytosol and the SR
      through a system by which the Ca2+ pool in the SR is restored by uptake of
      extracellular Ca2+ via a specific channel on the plasma membrane. This channel is
      called the store-operated Ca2+ channel or the Ca2+ release-activated Ca2+
      channel. It is activated by depletion of the Ca2+ store in the SR by coordination
      of two main molecules: stromal interaction molecule 1 (STIM1) and calcium release
      activated calcium channel protein 1 (ORAI1). Recently, myopathies with a dominant
      mutation in these genes have been reported and the pathogenic mechanism of such
      diseases have been proposed. This review overviews the calcium signaling in
      skeletal muscles and role of store-operated Ca2+ entry in calcium homeostasis.
      Finally, we discuss the phenotypes and the pathomechanism of myopathies caused by
      mutations in the STIM1 and ORAI1 genes.

PMID- 27879679
TI  - Hydrostatin-TL1, an Anti-Inflammatory Active Peptide from the Venom Gland of
      Hydrophis cyanocinctus in the South China Sea.
AB  - Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine with intense pro
      inflammatory and immunomodulatory properties, and anti-TNF-alpha biologics are
      effective therapies for various inflammatory diseases such as inflammatory bowel
      disease (IBD) and sepsis. Snake venom, as a traditional Chinese medicine, has
      been used in the treatment of inflammatory diseases in China for centuries. In
      this research, we constructed a venom gland T7 phage display library of the sea
      snake Hydrophis cyanocinctus to screen bioactive compounds that antagonize TNF
      alpha and identified a novel nine-amino-acid peptide, termed hydrostatin-TL1 (H
      TL1). In enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance
      (SPR) analyses, H-TL1 inhibited the interaction between TNF-alpha and TNF
      receptor 1 (TNFR1). Further, H-TL1 attenuated the cytotoxicity of TNF-alpha in
      L929 cells as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) assay. H-TL1 also decreased the mRNA expression of TNF
      alpha/TNFR1 downstream targets and suppressed the phosphorylation of well
      characterized proteins of downstream signal transduction pathways in HEK-293
      cells. In vivo data demonstrated that H-TL1 protects animals against dextran
      sodium sulfate (DSS)-induced acute colitis and lipopolysaccharide (LPS)-induced
      acute shock. Given its significant anti-inflammatory activity in vitro and in
      vivo, H-TL1 is a potential peptide for the development of new agents to treat TNF
      alpha-associated inflammatory diseases.

PMID- 27879680
TI  - Stereoselective Alkane Oxidation with meta-Chloroperoxybenzoic Acid (MCPBA)
      Catalyzed by Organometallic Cobalt Complexes.
AB  - Cobalt pi-complexes, previously described in the literature and specially
      synthesized and characterized in this work, were used as catalysts in homogeneous
      oxidation of organic compounds with peroxides. These complexes contain pi
      butadienyl and pi-cyclopentadienyl ligands:
      [(tetramethylcyclobutadiene)(benzene)cobalt] hexafluorophosphate,
      [(C4Me4)Co(C6H6)]PF6 (1); diiodo(carbonyl)(pentamethylcyclopentadienyl)cobalt,
      Cp*Co(CO)I2 (2); diiodo(carbonyl)(cyclopentadienyl)cobalt, CpCo(CO)I2 (3);
      (tetramethylcyclobutadiene)(dicarbonyl)(iodo)cobalt, (C4Me4)Co(CO)2I (4);
      [(tetramethylcyclobutadiene)(acetonitrile)(2,2'-bipyridyl)cobalt]
      hexafluorophosphate, [(C4Me4)Co(bipy)(MeCN)]PF6 (5); bis[dicarbonyl(B
      cyclohexylborole)]cobalt, [(C4H4BCy)Co(CO)2]2 (6);
      [(pentamethylcyclopentadienyl)(iodo)(1,10-phenanthroline)cobalt]
      hexafluorophosphate, [Cp*Co(phen)I]PF6 (7); diiodo(cyclopentadienyl)cobalt,
      [CpCoI2]2 (8); [(cyclopentadienyl)(iodo)(2,2'-bipyridyl)cobalt]
      hexafluorophosphate, [CpCo(bipy)I]PF6 (9); and
      [(pentamethylcyclopentadienyl)(iodo)(2,2'-bipyridyl)cobalt] hexafluorophosphate,
      [Cp*Co(bipy)I]PF6 (10). Complexes 1 and 2 catalyze very efficient and
      stereoselective oxygenation of tertiary C-H bonds in isomeric
      dimethylcyclohexanes with MCBA: cyclohexanols are produced in 39 and 53% yields
      and with the trans/cis ratio (of isomers with mutual trans- or cis-configuration
      of two methyl groups) 0.05 and 0.06, respectively. Addition of nitric acid as co
      catalyst dramatically enhances both the yield of oxygenates and stereoselectivity
      parameter. In contrast to compounds 1 and 2, complexes 9 and 10 turned out to be
      very poor catalysts (the yields of oxygenates in the reaction with cis-1,2
      dimethylcyclohexane were only 5%-7% and trans/cis ratio 0.8 indicated that the
      oxidation is not stereoselective). The chromatograms of the reaction mixture
      obtained before and after reduction with PPh3 are very similar, which testifies
      that alkyl hydroperoxides are not formed in this oxidation. It can be thus
      concluded that the interaction of the alkanes with MCPBA occurs without the
      formation of free radicals. The complexes catalyze oxidation of alcohols with
      tert-butylhydroperoxide (TBHP). For example, tert-BuOOH efficiently oxidizes 1
      phenylethanol to acetophenone in 98% yield if compound 1 is used as a catalyst.

PMID- 27879681
TI  - Kuwanon G Preserves LPS-Induced Disruption of Gut Epithelial Barrier In Vitro.
AB  - Defects in the gut epithelial barrier have now been recognized to be responsible
      for diabetic endotoxemia. In everyday life, Mulberry leaf tea is widely used in
      Asian nations due to its proposed benefits to health and control of diabetes.
      Evidence indicates the potential role of Kuwanon G (KWG), a component from Morus
      alba L., on blocking the gut epithelial barrier. In lipopolysaccharides (LPS)
      damaged Caco-2 cells, it was found that KWG increased the viability of cells in a
      concentration-dependent manner. KWG administration significantly elevated the
      anti-oxidant abilities via increasing ratio of superoxidase dismutase
      (SOD)/malondialdehyde (MDA) and decreasing reactive oxygen species (ROS) within
      the cells. During KWG incubation, pro-inflammatory cytokines including
      interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha were significantly
      reduced, tight junction proteins including zonula occludens (ZO)-1, intercellular
      adhesion molecule (ICAM)-1 and Occludin were dramatically increased as detected
      by immunofluorescence assay, trans-epithelial electrical resistance was
      significantly increased and the transmission of albumin-fluorescein
      isothiocyanate (FITC) across the barrier was decreased. In conclusion, the
      present study demonstrated that KWG could ameliorate LPS-induced disruption of
      the gut epithelial barrier by increasing cell viability and tight junction
      between cells, and decreasing pro-inflammatory cytokines and oxidative damage.

PMID- 27879682
TI  - Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells
      through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic
      Apoptosis.
AB  - BACKGROUND: Due to the aggressive clinical behavior, poor outcome, and lack of
      effective specific targeted therapies, triple-negative breast cancer (TNBC) has
      currently been recognized as one of the most malignant types of tumors. In the
      present study, we investigated the cytotoxic effect of ziyuglycoside I, one of
      the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae,
      on the TNBC cell line MDA-MB-231. METHODS: The underlying molecular mechanism of
      the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with
      cell viability assay, flow cytometric analysis and Western blot. RESULTS:
      Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I
      resulted in a significant growth inhibitory effect on MDA-MB-231 cells.
      Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells
      in a dose-dependent manner. These effects were found to be partially mediated
      through the up-regulation of p53 and p21WAF1, elevated Bax/Bcl-2 ratio, and the
      activation of both intrinsic (mitochondrial-initiated) and extrinsic (Fas/FasL
      initiated) apoptotic pathways. Furthermore, the p53 specific siRNA attenuated
      these effects. CONCLUSION: Our study suggested that ziyuglycoside I-triggered MDA
      MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This
      suggests that ziyuglycoside I might be a potential drug candidate for treating
      TNBC.

PMID- 27879683
TI  - Synthesis and Evaluation of New Benzodioxole- Based Thiosemicarbazone Derivatives
      as Potential Antitumor Agents.
AB  - New benzodioxole-based thiosemicarbazone derivatives were synthesized and
      evaluated for their cytotoxic effects on A549 human lung adenocarcinoma, C6 rat
      glioma and NIH/3T3 mouse embryonic fibroblast cells. In order to examine the
      correlation between anticancer activity and cholinesterases, the compounds were
      evaluated for their inhibitory effects on AChE and BuChE. The most effective
      anticancer agents were investigated for their effects on DNA synthesis, apoptosis
      and mitochondrial membrane potential. 4-(1,3-Benzodioxol-5-yl)-1-([1,1'-biphenyl]
      4-ylmethylene)thiosemicarbazide (5) was identified as the most promising
      anticancer agent against C6 and A549 cell lines due to its inhibitory effects on
      C6 and A549 cells and low toxicity to NIH/3T3 cells. Compound 5 increased early
      and late apoptosis in A549 and C6 cells. Compound 5 also caused disturbance on
      mitochondrial membrane potential and showed DNA synthesis inhibitory activity in
      A549 and C6 cells. Compound 5 was investigated for SIRT1 inhibitory activity to
      provide mechanistic insight and for that purpose docking studies were also
      performed for this compound on SIRT1. On the other hand, compound 5 did not show
      any inhibitory activity against AChE and BuChE. This outcome pointed out that
      there is no relationship between anticancer activity of compound 5 and
      cholinesterases.

PMID- 27879685
TI  - Synthesis and Biological Evaluation of Benzimidazole Phenylhydrazone Derivatives
      as Antifungal Agents against Phytopathogenic Fungi.
AB  - A series of benzimidazole phenylhydrazone derivatives (6a-6ai) were synthesized
      and characterized by 1H-NMR, ESI-MS, and elemental analysis. The structure of 6b
      was further confirmed by single crystal X-ray diffraction as (E)-configuration.
      All the compounds were screened for antifungal activity against Rhizoctonia
      solani and Magnaporthe oryzae employing a mycelium growth rate method. Compound
      6f exhibited significant inhibitory activity against R. solani and M. oryzae with
      the EC50 values of 1.20 and 1.85 MUg/mL, respectively. In vivo testing
      demonstrated that 6f could effectively control the development of rice sheath
      blight (RSB) and rice blast (RB) caused by the above two phytopathogens. This
      work indicated that the compound 6f with a benzimidazole phenylhydrazone scaffold
      could be considered as a leading structure for the development of novel
      fungicides.

PMID- 27879687
TI  - Images from Bits: Non-Iterative Image Reconstruction for Quanta Image Sensors.
AB  - A quanta image sensor (QIS) is a class of single-photon imaging devices that
      measure light intensity using oversampled binary observations. Because of the
      stochastic nature of the photon arrivals, data acquired by QIS is a massive
      stream of random binary bits. The goal of image reconstruction is to recover the
      underlying image from these bits. In this paper, we present a non-iterative image
      reconstruction algorithm for QIS. Unlike existing reconstruction methods that
      formulate the problem from an optimization perspective, the new algorithm
      directly recovers the images through a pair of nonlinear transformations and an
      off-the-shelf image denoising algorithm. By skipping the usual optimization
      procedure, we achieve orders of magnitude improvement in speed and even better
      image reconstruction quality. We validate the new algorithm on synthetic
      datasets, as well as real videos collected by one-bit single-photon avalanche
      diode (SPAD) cameras.

PMID- 27879686
TI  - Goal Pursuit in Youth with Chronic Pain.
AB  - Children and adolescents frequently experience chronic pain that can disrupt
      their usual activities and lead to poor physical and emotional functioning. The
      fear avoidance model of pain with an emphasis on the maladaptive behaviors that
      lead to activity avoidance has guided research and clinical practice. However,
      this model does not take into consideration variability in responses to pain, in
      particular the active pursuit of goals despite pain. This review aims to
      introduce a novel conceptualization of children's activity engagement versus
      avoidance using the framework of goal pursuit. We propose a new model of Goal
      Pursuit in Pediatric Chronic Pain, which proposes that the child's experience of
      pain is modified by child factors (e.g., goal salience, motivation/energy, pain
      related anxiety/fear, and self-efficacy) and parent factors (e.g., parent
      expectations for pain, protectiveness behaviors, and parent anxiety), which lead
      to specific goal pursuit behaviors. Goal pursuit is framed as engagement or
      avoidance of valued goals when in pain. Next, we recommend that research in youth
      with chronic pain should be reframed to account for the pursuit of valued goals
      within the context of pain and suggest directions for future research.

PMID- 27879684
TI  - Role of Osteogenic Growth Peptide (OGP) and OGP(10-14) in Bone Regeneration: A
      Review.
AB  - Bone regeneration is a process that involves several molecular mediators, such as
      growth factors, which directly affect the proliferation, migration and
      differentiation of bone-related cells. The osteogenic growth peptide (OGP) and
      its C-terminal pentapeptide OGP(10-14) have been shown to stimulate the
      proliferation, differentiation, alkaline phosphatase activity and matrix
      mineralization of osteoblastic lineage cells. However, the exact molecular
      mechanisms that promote osteoblastic proliferation and differentiation are not
      completely understood. This review presents the main chemical characteristics of
      OGP and/or OGP(10-14), and also discusses the potential molecular pathways
      induced by these growth factors to promote proliferation and differentiation of
      osteoblasts. Furthermore, since these peptides have been extensively investigated
      for bone tissue engineering, the clinical applications of these peptides for bone
      regeneration are discussed.

PMID- 27879688
TI  - IEEE 802.11ah: A Technology to Face the IoT Challenge.
AB  - Since the conception of the Internet of things (IoT), a large number of promising
      applications and technologies have been developed, which will change different
      aspects in our daily life. This paper explores the key characteristics of the
      forthcoming IEEE 802.11ah specification. This future IEEE 802.11 standard aims to
      amend the IEEE 802.11 legacy specification to support IoT requirements. We
      present a thorough evaluation of the foregoing amendment in comparison to the
      most notable IEEE 802.11 standards. In addition, we expose the capabilities of
      future IEEE 802.11ah in supporting different IoT applications. Also, we provide a
      brief overview of the technology contenders that are competing to cover the IoT
      communications framework. Numerical results are presented showing how the future
      IEEE 802.11ah specification offers the features required by IoT communications,
      thus putting forward IEEE 802.11ah as a technology to cater the needs of the
      Internet of Things paradigm.

PMID- 27879690
TI  - Geographical and Temporal Variations in Female Breast Cancer Mortality in the
      Municipalities of Andalusia (Southern Spain).
AB  - The last published figures have shown geographical variations in mortality with
      respect to female breast cancer in European countries. However, national health
      policies need a dynamic image of the geographical variations within the country.
      The aim of this paper was to describe the spatial distribution of age-specific
      mortality rates from female breast cancer in the municipalities of Andalusia
      (southern Spain) and to analyze its evolution over time from 1981 to 2012. An
      ecological study was devised. Two spatio-temporal hierarchical Bayesian models
      were estimated. One of these was used to estimate the age-specific mortality rate
      for each municipality, together with its time trends, and the other was used to
      estimate the age-specific rate ratio compared with Spain as a whole. The results
      showed that 98% of the municipalities exhibited a decreasing or a flat mortality
      trend for all the age groups. In 2012, the geographical variability of the age
      specific mortality rates was small, especially for population groups below 65. In
      addition, more than 96.6% of the municipalities showed an age-specific mortality
      rate similar to the corresponding rate for Spain, and there were no identified
      significant clusters. This information will contribute towards a reflection on
      the past, present and future of breast cancer outcomes in Andalusia.

PMID- 27879689
TI  - Determinants, Health Problems, and Food Insecurity in Urban Areas of the Largest
      City in Cape Verde.
AB  - Urbanization processes are intertwined with nutritional transition because there
      is easier access to food of low nutritional quality at reduced prices, changing
      dietary patterns and leading to an increase of non-communicable chronic diseases.
      This study aims to understand the perceptions for high blood pressure, obesity,
      and alcoholism, describing some interactions of these dimensions in the problem
      of food security in the city of Praia. A qualitative study was carried out under
      the framework of the research project "UPHI-STAT: Urban Planning and Health
      Inequalities-moving from macro to micro statistics". Ten focus groups were
      conducted in three urban areas with distinct characteristics in the city of
      Praia, with a total of 48 participants. Participants reported frequent
      consumption of foods with poor nutritional quality, understanding the potential
      danger in terms of food security in the city of Praia. Easy access to and high
      levels of alcohol consumption, and poor quality of traditional drinks were
      mentioned by participants in the study areas. The impact of the economic
      situation on the possibility of access to safe and healthy options emerged as a
      differentiating factor.

PMID- 27879692
TI  - Development of an Earthquake Early Warning System Using Real-Time Strong Motion
      Signals.
AB  - As urbanization progresses worldwide, earthquakes pose serious threat to livesand
      properties for urban areas near major active faults on land or subduction
      zonesoffshore. Earthquake Early Warning (EEW) can be a useful tool for reducing
      earthquakehazards, if the spatial relation between cities and earthquake sources
      is favorable for suchwarning and their citizens are properly trained to respond
      to earthquake warning messages.An EEW system forewarns an urban area of
      forthcoming strong shaking, normally with afew sec to a few tens of sec of
      warning time, i.e., before the arrival of the destructive Swavepart of the strong
      ground motion. Even a few second of advanced warning time willbe useful for pre
      programmed emergency measures for various critical facilities, such asrapid
      transit vehicles and high-speed trains to avoid potential derailment; it will be
      alsouseful for orderly shutoff of gas pipelines to minimize fire hazards,
      controlled shutdown ofhigh-technological manufacturing operations to reduce
      potential losses, and safe-guardingof computer facilities to avoid loss of vital
      databases. We explored a practical approach toEEW with the use of a ground-motion
      period parameter tauc and a high-pass filtered verticaldisplacement amplitude
      parameter Pd from the initial 3 sec of the P waveforms. At a givensite, an
      earthquake magnitude could be determined from tauc and the peak ground
      motionvelocity (PGV) could be estimated from Pd. In this method, incoming strong
      motion acceleration signals are recursively converted to ground velocity and
      displacement. A Pwavetrigger is constantly monitored. When a trigger occurs, tauc
      and Pd are computed. Theearthquake magnitude and the on-site ground-motion
      intensity could be estimated and thewarning could be issued. In an ideal
      situation, such warnings would be available within 10sec of the origin time of a
      large earthquake whose subsequent ground motion may last fortens of seconds.

PMID- 27879691
TI  - Overt Primary Hypothyroidism in an Industrial Area in Sao Paulo, Brazil: The
      Impact of Public Disclosure.
AB  - Background: Primary hypothyroidism (PH) is the most common thyroid pathology.
      Purpose: to evaluate the impact of public disclosure of an unexpected number of
      PH cases on the frequency of patients seeking medical evaluation for
      endocrinological diseases. Methods: data on 6306 subjects (3356 living in the
      surroundings of a petrochemical complex and 2950 in a control region) were
      collected over a 15-year time span. Thyroid function was determined by serum
      levels of triiodothyronine, thyroxine, free thyroxine and thyrotrophin.
      Antithyroglobulin and antithyroperoxidase antibodies and sonographic scans of the
      thyroid were performed in all patients. The data were analyzed via log-linear
      models to compute odds and odds ratios. Results: An increasing trend in the odds
      of PH was detected along the observation period with greater slope in the study
      region than in the control region. The odds of PH in the post-disclosure period
      (2002 to 2004) are greater than the corresponding ones in the pre-disclosure
      period (1989 to 2001). Conclusions: This study shows that living in the
      surroundings of a petrochemical complex may be an important risk factor for PH
      for both adults and children. Furthermore, public disclosure of such risk factor
      contributes to the awareness of the problem and to the possibility of an early
      diagnosis.

PMID- 27879694
TI  - Wavelength Dependence of Photoinduced Microcantilever Bending in the UV-VIS
      Range.
AB  - Micromechanical devices such as microcantilevers (MC) respond to irradiationwith
      light by at least two different, photon-mediated processes, which induce MC
      bendingas a consequence of differential surface stress. The first and slow
      bending is due to theabsorption of photons, whose energy is transformed into heat
      and causes bending ofbimetallic microcantilevers due to thermal expansion. The
      second type of deflection is fastand caused by photons of sufficient energy to
      promote electrons across the Schottky barrierand thus create charge carriers,
      resulting in photoinduced stress that causes MC bending. Inthis study, the MC
      bending response to irradiation with light of wavelengths ranging from250 to 700
      nm was investigated. Measurements of the immediate mechanical response
      tophotoinduced stress as a function of the wavelength of incident light provide
      an avenue tothe determination of the cut-off wavelength/energy of the Schottky
      barrier in the MCdevices under investigation. For a gold coated Si3Ni4
      microcantilever we measured a cutoffwavelength of 1206 nm, which lies in the
      range of the literature value of 1100 nm.

PMID- 27879693
TI  - Cantilever Micro-rheometer for the Characterization of Sugar Solutions.
AB  - The volume required for the rheological characterization of fluids can
      beminimized by using micromechanical cantilevers as viscosity sensors. Here, a
      simplemeasurement tool for the characterization of sugar solutions is proposed.
      The sensorconsists of a micromechanical cantilever as used in an atomic force
      microscopy which isintegrated into a closed fluid handling system. Fluid
      properties are derived from an analysisof the power spectral density of the
      fluctuations of the cantilever deflection signal. The dataacquisition system is
      operated with standard consumer computer components, which limitsthe costs for
      the hardware. Measurements with different sugar solutions indicate that thesensor
      system provides reliable viscosity values for sugar concentrations as they occur
      inbiological systems. The viscosities of the sugar solutions could be evaluated
      with an errorsmaller than 5 %.

PMID- 27879695
TI  - Input-output Transfer Function Analysis of a Photometer Circuit Based on an
      Operational Amplifier.
AB  - In this paper an input-output transfer function analysis based on the
      frequencyresponse of a photometer circuit based on operational amplifier (op amp)
      is carried out. Opamps are universally used in monitoring photodetectors and
      there are a variety of amplifierconnections for this purpose. However, the
      electronic circuits that are usually used to carryout the signal treatment in
      photometer circuits introduce some limitations in theperformance of the
      photometers that influence the selection of the op amps and otherelectronic
      devices. For example, the bandwidth, slew-rate, noise, input impedance and
      gain,among other characteristics of the op amp, are often the performance
      limiting factors ofphotometer circuits. For this reason, in this paper a
      comparative analysis between twophotodiode amplifier circuits is carried out. One
      circuit is based on a conventional currentto-voltage converter connection and the
      other circuit is based on a robust current-to-voltageconverter connection. The
      results are satisfactory and show that the photodiode amplifierperformance can be
      improved by using robust control techniques.

PMID- 27879696
TI  - Changes in Spectral Properties, Chlorophyll Content and Internal Mesophyll
      Structure of Senescing Populus balsamifera and Populus tremuloides Leaves.
AB  - In this paper we compare leaf traits and spectral reflectance for sunlit
      andshaded leaves of Populus tremuloides and Populus balsamifera during
      autumnsenescence using information derived from an Analytical Spectral Devise
      (ASD) FullRange spectrometer. The modified simple ratio (mSR705) and modified
      normalizeddifference index (mND705) were effective in describing changes in
      chlorophyll contentover this period. Highly significant (P less than 0.01)
      correlation coefficients were found betweenthe chlorophyll indices (mSR705,
      mND705)) and chlorophyll a, b, total chlorophyll andchlorophyll a/b. Changes in
      mesophyll structure were better described by the plantsenescence reflectance
      index (PSRI) than by near-infrared wavebands. Overall, P.balsamifera exhibited
      lower total chlorophyll and earlier senescence than P. tremuloides.Leaves of P.
      balsamifera were also thicker, had a higher proportion of intercellular spacein
      the spongy mesophyll, and higher reflectance at 800 nm. Further research, using
      largersample sizes over a broader range of sites will extend our understanding of
      the spectraland temporal dynamics of senescence in P. tremuloides and P.
      balsamifera and will beparticularly useful if species differences are detectable
      at the crown level using remotelysensed imagery.

PMID- 27879697
TI  - Assessment of Evapotranspiration and Soil Moisture Content Across Different
      Scales of Observation.
AB  - The proper assessment of evapotranspiration and soil moisture content
      arefundamental in food security research, land management, pollution detection,
      nutrient flows,(wild-) fire detection, (desert) locust, carbon balance as well as
      hydrological modelling; etc.This paper takes an extensive, though not exhaustive
      sample of international scientificliterature to discuss different approaches to
      estimate land surface and ecosystem relatedevapotranspiration and soil moisture
      content. This review presents:(i) a summary of the generally accepted cohesion
      theory of plant water uptake andtransport including a shortlist of meteorological
      and plant factors influencing planttranspiration;(ii) a summary on
      evapotranspiration assessment at different scales of observation
      (sapflow,porometer, lysimeter, field and catchment water balance, Bowen
      ratio,scintillometer, eddy correlation, Penman-Monteith and related
      approaches);(iii) a summary on data assimilation schemes conceived to estimate
      evapotranspirationusing optical and thermal remote sensing; and(iv) for soil
      moisture content, a summary on soil moisture retrieval techniques atdifferent
      spatial and temporal scales is presented.Concluding remarks on the best available
      approaches to assess evapotranspiration and soilmoisture content with and
      emphasis on remote sensing data assimilation, are provided.

PMID- 27879699
TI  - Electronic Nose Based on Metal Oxide Semiconductor Sensors as an Alternative
      Technique for the Spoilage Classification of Red Meat.
AB  - The aim of the present study was to develop an electronic nose for the quality
      control of red meat. Electronic nose and bacteriological measurements are
      performed to analyse samples of beef and sheep meat stored at 4 degrees C for up
      to 15 days. Principal component analysis (PCA) and support vector machine (SVM)
      based classification techniques are used to investigate the performance of the
      electronic nose system in the spoilage classification of red meats. The
      bacteriological method was selected as the reference method to consistently train
      the electronic nose system. The SVM models built classified meat samples based on
      the total microbial population into "unspoiled" (microbial counts < 6 log10
      cfu/g) and "spoiled" (microbial counts >= 6 log10 cfu/g). The preliminary results
      obtained by the bacteria total viable counts (TVC) show that the shelf-life of
      beef and sheep meats stored at 4  degrees C are 7 and 5 days, respectively. The
      electronic nose system coupled to SVM could discriminate between unspoiled/
      spoiled beef or sheep meats with a success rate of 98.81 or 96.43 %,
      respectively. To investigate whether the results of the electronic nose
      correlated well with the results of the bacteriological analysis, partial least
      squares (PLS) calibration models were built and validated. Good correlation
      coefficients between the electronic nose signals and bacteriological data were
      obtained, a clear indication that the electronic nose system can become a simple
      and rapid technique for the quality control of red meats.

PMID- 27879700
TI  - Lightning Sensors for Observing, Tracking and Nowcasting Severe Weather.
AB  - Severe and extreme weather is a major natural hazard all over the world,
      oftenresulting in major natural disasters such as hail storms, tornados, wind
      storms, flash floods,forest fires and lightning damages. While precipitation,
      wind, hail, tornados, turbulence,etc. can only be observed at close distances,
      lightning activity in these damaging stormscan be monitored at all spatial
      scales, from local (using very high frequency [VHF]sensors), to regional (using
      very low frequency [VLF] sensors), and even global scales(using extremely low
      frequency [ELF] sensors). Using sensors that detect the radio wavesemitted by
      each lightning discharge, it is now possible to observe and track
      continuouslydistant thunderstorms using ground networks of sensors. In addition
      to the number oflightning discharges, these sensors can also provide information
      on lightningcharacteristics such as the ratio between intra-cloud and cloud-to
      ground lightning, thepolarity of the lightning discharge, peak currents, charge
      removal, etc. It has been shownthat changes in some of these lightning
      characteristics during thunderstorms are oftenrelated to changes in the severity
      of the storms. In this paper different lightning observingsystems are described,
      and a few examples are provided showing how lightning may beused to monitor storm
      hazards around the globe, while also providing the possibility ofsupplying short
      term forecasts, called nowcasting.

PMID- 27879701
TI  - Chemical Sensing Sensitivity of Long-Period Grating Sensor Enhanced by Colloidal
      Gold Nanoparticles.
AB  - A simple and effective method is proposed to improve spectral sensitivity
      anddetection limit of long period gratings for refractive index or chemical
      sensing, where thegrating surface is modified by a monolayer of colloidal gold
      nanoparticles. Thetransmission spectra and optical properties of gold nanospheres
      vary with the differentrefractive index of the environment near the surface of
      gold nanospheres. The sensorresponse of gold colloids increases linearly with
      solvents of increasing refractive index.The results for the measurement of
      sucrose and sodium chloride solutions are reported,which show that this type of
      sensor can provide a limiting resolution of ~10-3 to ~10-4 forrefractive indices
      in the range of 1.34 to 1.39 and a noticeable increase in detection limit
      ofrefractive index to external medium.

PMID- 27879698
TI  - Electrochemical Sensors Based on Organic Conjugated Polymers.
AB  - Organic conjugated polymers (conducting polymers) have emerged as
      potentialcandidates for electrochemical sensors. Due to their straightforward
      preparation methods,unique properties, and stability in air, conducting polymers
      have been applied to energystorage, electrochemical devices, memory devices,
      chemical sensors, and electrocatalysts.Conducting polymers are also known to be
      compatible with biological molecules in aneutral aqueous solution. Thus, these
      are extensively used in the fabrication of accurate,fast, and inexpensive
      devices, such as biosensors and chemical sensors in the medicaldiagnostic
      laboratories. Conducting polymer-based electrochemical sensors and biosensorsplay
      an important role in the improvement of public health and environment because
      rapiddetection, high sensitivity, small size, and specificity are achievable for
      environmentalmonitoring and clinical diagnostics. In this review, we summarized
      the recent advances inconducting polymer-based electrochemical sensors, which
      covers chemical sensors(potentiometric, voltammetric, amperometric) and
      biosensors (enzyme based biosensors,immunosensors, DNA sensors).

PMID- 27879702
TI  - Fabrication of a ZnO Pyroelectric Sensor.
AB  - This paper proposes a two-step radio frequency (RF) sputtering process to forma
      ZnO film for pyroelectric sensors. It is shown that the two-step sputtering
      process with alower power step followed by a higher power step can significantly
      improve the voltageresponsivity of the ZnO pyroelectric sensor. The improvement
      is attributed mainly to theformation of ZnO film with a strongly preferred
      orientation towards the c-axis.Furthermore, a nickel film deposited onto the
      uncovered parts of the ZnO film caneffectively improve the voltage responsivity
      at higher modulating frequencies since thenickel film can enhance the incident
      energy absorption of the ZnO layer.

PMID- 27879704
TI  - Application of Design of Experiment Method for Thrust Force Minimization in Step
      feed Micro Drilling.
AB  - Micro drilled holes are utilized in many of today's fabrication
      processes.Precision production processes in industries are trending toward the
      use of smaller holeswith higher aspect ratios, and higher speed operation for
      micro deep hole drilling. However,undesirable characteristics related to micro
      drilling such as small signal-to-noise ratios,wandering drill motion, high aspect
      ratio, and excessive cutting forces can be observedwhen cutting depth increases.
      In this study, the authors attempt to minimize the thrustforces in the step-feed
      micro drilling process by application of the DOE (Design ofExperiment) method.
      Taking into account the drilling thrust, three cutting parameters,feedrate, step
      feed, and cutting speed, are optimized based on the DOE method. Forexperimental
      studies, an orthogonal array L27(313) is generated and ANOVA (Analysis
      ofVariance) is carried out. Based on the results it is determined that the
      sequence of factorsaffecting drilling thrusts corresponds to feedrate, step-feed,
      and spindle rpm. Acombination of optimal drilling conditions is also identified.
      In particular, it is found in thisstudy that the feedrate is the most important
      factor for micro drilling thrust minimization.

PMID- 27879703
TI  - Enzyme-Linked Electrochemical Detection of PCR-Amplified Nucleotide Sequences
      Using Disposable Screen-Printed Sensors. Applications in Gene Expression
      Monitoring.
AB  - Electrochemical enzyme-linked techniques for sequence-specific DNA sensingare
      presented. These techniques are based on attachment of streptavidin
      alkalinephosphatase conjugate to biotin tags tethered to DNA immobilized at the
      surface ofdisposable screen-printed carbon electrodes (SPCE), followed by
      production andelectrochemical determination of an electroactive indicator, 1
      naphthol. Via hybridizationof SPCE surface-confined target DNAs with end
      biotinylated probes, highly specificdiscrimination between complementary and non
      complementary nucleotide sequences wasachieved. The enzyme-linked DNA
      hybridization assay has been successfully applied inanalysis of PCR-amplified
      real genomic DNA sequences, as well as in monitoring of planttissue-specific gene
      expression. In addition, we present an alternative approach involvingsequence
      specific incorporation of biotin-labeled nucleotides into DNA by primerextension.
      Introduction of multiple biotin tags per probe primer resulted in
      considerableenhancement of the signal intensity and improvement of the
      specificity of detection.

PMID- 27879705
TI  - Experimental Study on the Effects of Alumina Abrasive Particle Behavior in MR
      Polishing for MEMS Applications.
AB  - Recently, the magnetorheological (MR) polishing process has been examined asa new
      ultra-precision polishing technology for micro parts in MEMS applications. In
      theMR polishing process, the magnetic force plays a dominant role. This method
      uses MRfluids which contains micro abrasives as a polishing media. The objective
      of the presentresearch is to shed light onto the material removal mechanism under
      various slurryconditions for polishing and to investigate surface
      characteristics, including shape analysisand surface roughness measurement, of
      spots obtained from the MR polishing process usingalumina abrasives. A series of
      basic experiments were first performed to determine theoptimum polishing
      conditions for BK7 glass using prepared slurries by changing the
      processparameters, such as wheel rotating speed and electric current. Using the
      obtained results,groove polishing was then performed and the results are
      investigated. Outstanding surfaceroughness of Ra=3.8nm was obtained on the BK7
      glass specimen. The present resultshighlight the possibility of applying this
      polishing method to ultra-precision micro partsproduction, especially in MEMS
      applications.

PMID- 27879706
TI  - Advances in Remote Sensing for Oil Spill Disaster Management: State-of-the-Art
      Sensors Technology for Oil Spill Surveillance.
AB  - Reducing the risk of oil spill disasters is essential for protecting the
      environmentand reducing economic losses. Oil spill surveillance constitutes an
      important component ofoil spill disaster management. Advances in remote sensing
      technologies can help to identifyparties potentially responsible for pollution
      and to identify minor spills before they causewidespread damage. Due to the large
      number of sensors currently available for oil spillsurveillance, there is a need
      for a comprehensive overview and comparison of existingsensors. Specifically,
      this paper examines the characteristics and applications of differentsensors. A
      better understanding of the strengths and weaknesses of oil spill
      surveillancesensors will improve the operational use of these sensors for oil
      spill response andcontingency planning. Laser fluorosensors were found to be the
      best available sensor for oilspill detection since they not only detect and
      classify oil on all surfaces but also operate ineither the day or night. For
      example, the Scanning Laser Environmental AirborneFluorosensor (SLEAF) sensor was
      identified to be a valuable tool for oil spill surveillance.However, no single
      sensor was able to provide all information required for oil spillcontingency
      planning. Hence, combinations of sensors are currently used for oil
      spillsurveillance. Specifically, satellite sensors are used for preliminary oil
      spill assessmentwhile airborne sensors are used for detailed oil spill analysis.
      While satellite remote sensingis not suitable for tactical oil spill planning it
      can provide a synoptic coverage of theaffected area.

PMID- 27879707
TI  - Soil Moisture Profile Effect on Radar Signal Measurement.
AB  - The objective of this paper is to analyze the behaviour of a backscattered
      signalaccording to soil moisture depth over bare soils. Analysis based on
      experimental verticalmoisture profiles and ASAR/ENVISAT measurements has been
      carried out. A modifiedIEM model with three permittivity layers (0-1cm, 1-2cm, 2
      5cm) has been developed andused in this study. Results show a small effect of
      moisture profile on the backscatteredsignal (less than 0.5dB). However,
      measurements and simulations have provided a moredetailed insight into the
      behaviour of the radar signal and have shown that it was importantto consistently
      use the same protocol when performing ground truth measurements of soilmoisture.

PMID- 27879708
TI  - Application of Multiplexed FBG and PZT Impedance Sensors for Health Monitoring of
      Rocks.
AB  - Reliable structural health monitoring (SHM) including nondestructiveevaluation
      (NDE) is essential for safe operation of infrastructure systems.
      Effectivemonitoring of the rock components of civil infrastructures such as
      tunnels and cavernsremains challenging. The feasibility of employing smart
      optical fibre sensor (OFS) andpiezoelectric impedance sensor made up of lead
      zirconate titanate (PZT) forcomprehensive health monitoring of rocks, covering
      load history monitoring/retrieval aswell as damage assessment is presented in
      this paper. The rock specimens are subjected tocyclic loading and their
      conditions are continuously monitored using OFS and PZTsensors. OFS based
      multiplexed fibre Bragg grating (FBG) sensors are surface bonded onthe rock
      specimens. Their strain sensing performance is compared with the
      conventionalelectric strain gauges (ESGs). In addition, PZT patches are also
      bonded on the specimensto study the damage pattern during different loading
      cycles. Unlike the FBGs or ESGs,PZT patches are used as bi-functional sensors and
      actuators, enabling them to be efficientdetectors of incipient damages using the
      principle of electromechanical impedance. Theexperimental study demonstrated
      superior performance of these smart FBG and PZTimpedance sensors. This work is
      expected to be useful for SHM based NDE application ofrock structures such as
      caverns and tunnels.

PMID- 27879709
TI  - A Review on the Electrochemical Sensors and Biosensors Composed of Nanowires as
      Sensing Material.
AB  - The development and application of nanowires for electrochemical sensors and
      biosensors are reviewed in this article. Next generation sensor platforms will
      require significant improvements in sensitivity, specificity and parallelism in
      order to meet the future needs in variety of fields. Sensors made of nanowires
      exploit some fundamental nanoscopic effect in order to meet these requirements.
      Nanowires are new materials, which have the characteristic of low weight with
      extraordinary mechanical, electrical, thermal and multifunctional properties. The
      advantages such as size scale, aspect ratio and other properties of nanowires are
      especially apparent in the use of electrical sensors such as electrochemical
      sensors and in the use of field-effect transistors. The preparation methods of
      nanowires and their properties are discussed along with their advantages towards
      electrochemical sensors and biosensors. Some key results from each article are
      summarized, relating the concept and mechanism behind each sensor, with
      experimental conditions as well as their behavior at different conditions.

PMID- 27879710
TI  - Ad Hoc Modeling of Root Zone Soil Water with Landsat Imagery and Terrain and
      Soils Data.
AB  - Agricultural producers require knowledge of soil water at plant rooting
      depths,while many remote sensing studies have focused on surface soil water or
      mechanisticmodels that are not easily parameterized. We developed site-specific
      empirical models topredict spring soil water content for two Montana ranches.
      Calibration data sample sizeswere based on the estimated variability of soil
      water and the desired level of precision forthe soil water estimates. Models used
      Landsat imagery, a digital elevation model, and asoil survey as predictor
      variables. Our objectives were to see whether soil water could bepredicted
      accurately with easily obtainable calibration data and predictor variables and
      toconsider the relative influence of the three sources of predictor variables.
      Independentvalidation showed that multiple regression models predicted soil water
      with average error(RMSD) within 0.04 mass water content. This was similar to the
      accuracy expected basedon a statistical power test based on our sample size (n =
      41 and n = 50). Improvedprediction precision could be achieved with additional
      calibration samples, and rangemanagers can readily balance the desired level of
      precision with the amount of effort tocollect calibration data. Spring soil water
      prediction effectively utilized a combination ofland surface imagery, terrain
      data, and subsurface soil characterization data. Rancherscould use accurate
      spring soil water content predictions to set stocking rates. Suchmanagement can
      help ensure that water, soil, and vegetation resources are usedconservatively in
      irrigated and non-irrigated rangeland systems.

PMID- 27879711
TI  - Sensitivity of PZT Impedance Sensors for Damage Detection of Concrete Structures.
AB  - Piezoelectric ceramic Lead Zirconate Titanate (PZT) based electro
      mechanicalimpedance (EMI) technique for structural health monitoring (SHM) has
      been successfullyapplied to various engineering systems. However, fundamental
      research work on thesensitivity of the PZT impedance sensors for damage detection
      is still in need. In thetraditional EMI method, the PZT electro-mechanical (EM)
      admittance (inverse of theimpedance) is used as damage indicator, which is
      difficult to specify the effect of damage onstructural properties. This paper
      uses the structural mechanical impedance (SMI) extractedfrom the PZT EM
      admittance signature as the damage indicator. A comparison study on
      thesensitivity of the EM admittance and the structural mechanical impedance to
      the damages ina concrete structure is conducted. Results show that the SMI is
      more sensitive to the damagethan the EM admittance thus a better indicator for
      damage detection. Furthermore, this paperproposes a dynamic system consisting of
      a number of single-degree-of-freedom elementswith mass, spring and damper
      components to model the SMI. A genetic algorithm isemployed to search for the
      optimal value of the unknown parameters in the dynamic system.An experiment is
      carried out on a two-storey concrete frame subjected to base vibrations
      thatsimulate earthquake. A number of PZT sensors are regularly arrayed and bonded
      to the framestructure to acquire PZT EM admittance signatures. The relationship
      between the damageindex and the distance of the PZT sensor from the damage is
      studied. Consequently, thesensitivity of the PZT sensors is discussed and their
      sensing region in concrete is derived.

PMID- 27879712
TI  - Biosensor Techniques Used for Determination of Telomerase Activity in Cancer
      Cells.
AB  - Measuring telomerase activity has proven successful for the determination of
      cancer in malignant somatic cells. Early conventional methods for the detection
      of telomerase activity include in vitro analysis via a primer extension assay,
      and the telomeric repeat amplification protocol (TRAP) assay. TRAP incorporates
      the polymerase chain reaction (PCR) step to increase the sensitivity of a given
      sample. However, research suggests that the TRAP technique suffers from false
      negative results, caused by failure of its PCR step. Other limitations of TRAP
      include the post-PCR steps involving polyacrylamide gel electrophoresis which are
      time inefficient. Thus, various efforts have been made to eliminate the PCR step
      of TRAP by using a variety of biosensor detection devices. This review mainly
      focuses on these alternatives including: optical, electrochemical, magnetic, and
      nanowire conductive signaling techniques to measure the telomerase activity
      produced via label free biosensor assay-via biocatalytic labels involving
      beacons, DNAzyme, ferrocenyl-naphthalene diimides, avidin-alkaline phosphatase
      and semiconductor quantum dots (QDs). These biosensor techniques are sensitive
      and provide precise and rapid results in the detection of telomerase activity.

PMID- 27879713
TI  - A Review of Interface Electronic Systems for AT-cut Quartz Crystal Microbalance
      Applications in Liquids.
AB  - From the first applications of AT-cut quartz crystals as sensors in solutionsmore
      than 20 years ago, the so-called quartz crystal microbalance (QCM) sensor
      isbecoming into a good alternative analytical method in a great deal of
      applications such asbiosensors, analysis of biomolecular interactions, study of
      bacterial adhesion at specificinterfaces, pathogen and microorganism detection,
      study of polymer film-biomolecule orcell-substrate interactions, immunosensors
      and an extensive use in fluids and polymercharacterization and electrochemical
      applications among others. The appropriateevaluation of this analytical method
      requires recognizing the different steps involved andto be conscious of their
      importance and limitations. The first step involved in a QCMsystem is the
      accurate and appropriate characterization of the sensor in relation to
      thespecific application. The use of the piezoelectric sensor in contact with
      solutions stronglyaffects its behavior and appropriate electronic interfaces must
      be used for an adequatesensor characterization. Systems based on different
      principles and techniques have beenimplemented during the last 25 years. The
      interface selection for the specific application isimportant and its limitations
      must be known to be conscious of its suitability, and foravoiding the possible
      error propagation in the interpretation of results. This article presentsa
      comprehensive overview of the different techniques used for AT-cut quartz
      crystalmicrobalance in in-solution applications, which are based on the following
      principles:network or impedance analyzers, decay methods, oscillators and lock-in
      techniques. Theelectronic interfaces based on oscillators and phase-locked
      techniques are treated in detail,with the description of different
      configurations, since these techniques are the most used inapplications for
      detection of analytes in solutions, and in those where a fast sensorresponse is
      necessary.

PMID- 27879714
TI  - Validating Evapotranspiraiton Equations Using Bowen Ratio in New Brunswick,
      Maritime, Canada.
AB  - Three methods including the Penman-Monteith (PM), Priestley-Taylor (PT), and 1963
      Penman equation (PE) for calculating daily reference evapotranspiration (ETo)
      were evaluated in the Maritime region of Canada with the data collected from 2004
      to 2007. An automatically operated meteorological station located on the Potato
      Research Centre, Agriculture and Agri-Food Canada, Fredericton, New Brunswick,
      Canada, was used to collect required meteorological data for evapotranspiration
      modeling. A Bowen Ratio system (BR) was setup near the Environment Canada grade
      one weather station to provide evapotranspiration observations for the validation
      research of reference evapotranspiration models. The results showed that the
      prediction from each of the tested models had a certain degree of offset in
      comparison with the observations obtained by the BR method. All of the tested
      models slightly overestimated evapotranspiration compared to the BR system by 5
      14%, depending on the method. However, the PM generated a better fit to the
      pooled dataset while the PT produced the best prediction for the 2007 validation
      dataset. The PM generated the best estimation of evapotranspiration for year 2004
      during a inter-annual comparison. The BR revealed that the average daytime ET for
      the site was around 2.5 mm day-1(+/-0.1) averaged for Julian day 157-276 in 2004
      to 2006 and possible condensation was 0.16 mm day-1 for the same period. Crop
      coefficient (Kc) varied with different models, for example, 0.42 for the PM, 0.44
      for the PT, and 0.67 for the PE with a slight yearly variation. With this set of
      Kc values, a validation with additional dataset collected in 2007 indicated that
      all three equations achieved a good fit with observations using the above Kc
      values. The PT performed slightly better than the other two models. A single
      factor analysis did not show any statistically significant difference between
      predicted and measured ET. With a consideration of simplicity and application for
      scaling up to landscape, this research suggested that the PT is the preferable
      method for estimating ET values in this region.

PMID- 27879715
TI  - Study of Copper and Purine-Copper Complexes on Modified Carbon Electrodes by
      Cyclic and Elimination Voltammetry.
AB  - Using a paraffin impregnated graphite electrode (PIGE) and mercury
      modifiedpyrolytic graphite electrode with basal orientation (Hg-PGEb) copper(II)
      and Cu(II)-DNApurine base solutions have been studied by cyclic (CV) and linear
      sweep voltammetry(LSV) in connection with elimination voltammetry with linear
      scan (EVLS). In chlorideand bromide solutions (pH 6), the redox process of Cu(II)
      proceeded on PIGE with twocathodic and two anodic potentially separated signals.
      According to the eliminationfunction E4, the first cathodic peak corresponds to
      the reduction Cu(II) e- -> Cu(I) withthe possibility of fast disproportionation
      2Cu(I) -> Cu(II) Cu(0). The E4 of the secondcathodic peak signalized an electrode
      process controlled by a surface reaction. Theelectrode system of Cu(II) on Hg
      PGEb in borate buffer (pH 9.2) was characterized by onecathodic and one anodic
      peak. Anodic stripping voltammetry (ASV) on PIGE and cathodicstripping
      voltammetry (CSV) on Hg-PGEb were carried out at potentials where thereduction of
      copper ions took place and Cu(I)-purine complexes were formed. By usingASV and
      CSV in combination with EVLS, the sensitivity of Cu(I)-purine complexdetection
      was enhanced relative to either ASV or CSV alone, resulting in higher
      peakcurrents of more than one order of magnitude. The statistical treatment of CE
      data wasused to determine the reproducibility of measurements. Our results show
      that EVLS inconnection with the stripping procedure is useful for both
      qualitative and quantitativemicroanalysis of purine derivatives and can also
      reveal details of studied electrodeprocesses.

PMID- 27879716
TI  - Multi-instrumental Analysis of Tissues of Sunflower Plants Treated with Silver(I)
      Ions - Plants as Bioindicators of Environmental Pollution.
AB  - The aim of this work is to investigate sunflower plants response on stressinduced
      by silver(I) ions. The sunflower plants were exposed to silver(I) ions (0, 0.1,
      0.5,and 1 mM) for 96 h. Primarily we aimed our attention to observation of basic
      physiologicalparameters. We found that the treated plants embodied growth
      depression, coloured changes and lack root hairs. Using of autofluorescence of
      anatomical structures, such aslignified cell walls, it was possible to determine
      the changes of important shoot and rootstructures, mainly vascular bungles and
      development of secondary thickening. Thedifferences in vascular bundles
      organisation, parenchymatic pith development in the rootcentre and the reduction
      of phloem part of vascular bundles were well observable.Moreover with increasing
      silver(I) ions concentration the vitality of rhizodermal cellsdeclined;
      rhizodermal cells early necrosed and were replaced by the cells of
      exodermis.Further we employed laser induced breakdown spectroscopy for
      determination of spatialdistribution of silver(I) ions in tissues of the treated
      plants. The Ag is accumulated mainlyin near-root part of the sample. Moreover
      basic biochemical indicators of environmentalstress were investigated. The total
      content of proteins expressively decreased withincreasing silver(I) ions dose and
      the time of the treatment. As we compare the resultsobtained by protein analysis 
      the total protein contents in shoot as well as root parts - wecan assume on the
      transport of the proteins from the roots to shoots. This phenomenon canbe related
      with the cascade of processes connecting with photosynthesis. The
      secondbiochemical parameter, which we investigated, was urease activity. If we
      compared theactivity in treated plants with control, we found out that presence
      of silver(I) ions markedlyenhanced the activity of urease at all applied doses of
      this toxic metal. Finally we studiedthe effect of silver(I) ions on activity of
      urease in in vitro conditions.

PMID- 27879717
TI  - Lactoferrin Isolation Using Monolithic Column Coupled with Spectrometric or Micro
      Amperometric Detector.
AB  - Lactoferrin is a multifunctional protein with antimicrobial activity and others
      tohealth beneficial properties. The main aim of this work was to propose easy to
      usetechnique for lactoferrin isolation from cow colostrum samples. Primarily we
      utilizedsodium dodecyl sulphate - polyacrylamide gel electrophoresis for
      isolation of lactoferrinfrom the real samples. Moreover we tested automated
      microfluidic Experionelectrophoresis system to isolate lactoferrin from the
      collostrum sample. The welldeveloped signal of lactoferrin was determined with
      detection limit (3 S/N) of 20 ng/ml. Inspite of the fact that Experion is faster
      than SDS-PAGE both separation techniques cannotbe used in routine analysis.
      Therefore we have tested third separation technique, ionexchange chromatography,
      using monolithic column coupled with UV-VIS detector (LCUV-VIS). We optimized
      wave length (280 nm), ionic strength of the elution solution (1.5M NaCl) and flow
      rate of the retention and elution solutions (0.25 ml/min and 0.75
      ml/min.respectively). Under the optimal conditions the detection limit was
      estimated as 0.1 MUg/mlof lactoferrin measured. Using LC-UV-VIS we determined
      that lactoferrin concentrationvaried from 0.5 g/l to 1.1 g/l in cow colostrums
      collected in the certain time interval up to 72 hours after birth. Further we
      focused on miniaturization of detection device. We testedamperometric detection
      at carbon electrode. The results encouraged us to attempt tominiaturise whole
      detection system and to test it on analysis of real samples of humanfaeces,
      because lactoferrin level in faeces is closely associated with the inflammations
      ofintestine mucous membrane. For the purpose of miniaturization we employed
      thetechnology of printed electrodes. The detection limit of lactoferrin was
      estimated as 10MUg/ml measured by the screen-printed electrodes fabricated by us.
      The fabricatedelectrodes were compared with commercially available ones. It
      follows from the obtainedresults that the responses measured by commercial
      electrodes are app. ten times highercompared with those measured by the
      electrodes fabricated by us. This phenomenonrelates with smaller working
      electrode surface area of the electrodes fabricated by us(about 50 %) compared to
      the commercial ones. The screen-printed electrodes fabricatedby us were utilized
      for determination of lactoferrin faeces. Regarding to fact that sample offaeces
      was obtained from young and healthy man the amount of lactoferrin in sample
      wasunder the limit of detection of this method.

PMID- 27879719
TI  - Thermal Degradation, Mechanical Properties and Morphology of Wheat Straw Flour
      Filled Recycled Thermoplastic Composites.
AB  - Thermal behaviors of wheat straw flour (WF) filled thermoplastic compositeswere
      measured applying the thermogravimetric analysis and differential
      scanningcalorimetry. Morphology and mechanical properties were also studied using
      scanningelectron microscope and universal testing machine, respectively. Presence
      of WF inthermoplastic matrix reduced the degradation temperature of the
      composites. One for WFand one for thermoplastics, two main decomposition peaks
      were observed. Morphologicalstudy showed that addition of coupling agent improved
      the compatibility between WFs andthermoplastic. WFs were embedded into the
      thermoplastic matrix indicating improvedadhesion. However, the bonding was not
      perfect because some debonding can also be seenon the interface of WFs and
      thermoplastic matrix. In the case of mechanical properties ofWF filled recycled
      thermoplastic, HDPE and PP based composites provided similar tensileand flexural
      properties. The addition of coupling agents improved the properties
      ofthermoplastic composites. MAPE coupling agents performed better in HDPE while
      MAPPcoupling agents were superior in PP based composites. The composites produced
      with thecombination of 50-percent mixture of recycled HDPE and PP performed
      similar with theuse of both coupling agents. All produced composites provided
      flexural properties requiredby the ASTM standard for polyolefin-based plastic
      lumber decking boards.

PMID- 27879720
TI  - The Tradeoff Analysis for Remote Sensing Image Fusion Using Expanded Spectral
      Angle Mapper.
AB  - Image fusion is a useful tool in integrating a high-resolution panchromaticimage
      (HRPI) with a low-resolution multispectral image (LRMI) to produce a
      highresolutionmultispectral image (HRMI). To date, many image fusion techniques
      have beendeveloped to try to improve the spatial resolution of the LRMI to that
      of the HRPI with itsspectral property reliably preserved. However, many studies
      have indicated that thereexists a trade- off between the spatial resolution
      improvement and the spectral propertypreservation of the LRMI, and it is
      difficult for the existing methods to do the best in bothaspects. Based on one
      minimization problem, this paper mathematically analyzes thetradeoff in fusing
      remote sensing images. In experiment, four fusion methods are evaluatedthrough
      expanded spectral angle mapper (ESAM). Results clearly prove that all the
      testedmethods have this property.

PMID- 27879718
TI  - Cytotoxicity Investigation on Cultured Human Blood Cells Treated with Single-Wall
      Carbon Nanotubes.
AB  - The single-wall carbon nanotubes (SWCNTs) are one of the new materials ofemerging
      technologies. They are becoming increasingly studied for the possibleapplications
      in electronics, optics and biology. In particular, very promising fields
      ofapplication are the development of optical biosensors and the intracellular
      drug delivery.Nevertheless, there is a paucity of information on their
      toxicological properties and onpotential human health risk. In the present study
      the SWCNTs were investigated for thepossible induction of toxicity in human blood
      cells. Cell growth, viability, apoptosis andmetabolic activity were evaluated in
      proliferating human peripheral blood lymphocytes. Inun-stimulated human
      leukocytes primary DNA damage was also evaluated. SWCNTsconcentrations ranging
      from 1 to 50 MUg/ml were tested, and treatment duration varied from6 to 72 h, in
      accordance with the biological target investigated. A statistically
      significantdecrease in cell growth was found in cells treated with the highest
      concentrations (25 and50 MUg/ml). Such decrease was not associated to cell death
      or apoptosis, but it wasdemonstrated to be related to a decrease in metabolic
      activity, as assessed by resazurinassay. Moreover, treatments of 6 h with SWCNTs
      concentrations of 1, 5 and 10 MUg/mlfailed to induce primary DNA damage on the
      entire human leukocytes population.

PMID- 27879721
TI  - Spatially Explicit Large Area Biomass Estimation: Three Approaches Using Forest
      Inventory and Remotely Sensed Imagery in a GIS.
AB  - Forest inventory data often provide the required base data to enable the
      largearea mapping of biomass over a range of scales. However, spatially explicit
      estimates ofabove-ground biomass (AGB) over large areas may be limited by the
      spatial extent of theforest inventory relative to the area of interest (i.e.,
      inventories not spatially exhaustive), orby the omission of inventory attributes
      required for biomass estimation. These spatial andattributional gaps in the
      forest inventory may result in an underestimation of large areaAGB. The
      continuous nature and synoptic coverage of remotely sensed data have led totheir
      increased application for AGB estimation over large areas, although the use of
      thesedata remains challenging in complex forest environments. In this paper, we
      present anapproach to generating spatially explicit estimates of large area AGB
      by integrating AGBestimates from multiple data sources; 1. using a lookup table
      of conversion factors appliedto a non-spatially exhaustive forest inventory
      dataset (R2 = 0.64; RMSE = 16.95 t/ha), 2.applying a lookup table to unique
      combinations of land cover and vegetation densityoutputs derived from remotely
      sensed data (R2 = 0.52; RMSE = 19.97 t/ha), and 3. hybridmapping by augmenting
      forest inventory AGB estimates with remotely sensed AGB estimates where there are
      spatial or attributional gaps in the forest inventory data. Over our714,852 ha
      study area in central Saskatchewan, Canada, the AGB estimate generated fromthe
      forest inventory was approximately 40 Mega tonnes (Mt); however, the
      inventoryestimate represents only 51% of the total study area. The AGB estimate
      generated from theremotely sensed outputs that overlap those made from the forest
      inventory based approachdiffer by only 2 %; however in total, the remotely sensed
      estimate is 30 % greater (58 Mt)than the estimate generated from the forest
      inventory when the entire study area isaccounted for. Finally, using the hybrid
      approach, whereby the remotely sensed inputswere used to fill spatial gaps in the
      forest inventory, the total AGB for the study area wasestimated at 62 Mt. In the
      example presented, data integration facilitates comprehensiveand spatially
      explicit estimation of AGB for the entire study area.

PMID- 27879722
TI  - Review on Hydrogel-based pH Sensors and Microsensors.
AB  - Stimuli-responsive hydrogels are materials with great potential for development
      of active functionalities in fluidics and micro-fluidics. Based on the current
      state of research on pH sensors, hydrogel sensors are described qualitatively and
      quantitatively for the first time. The review introduces the physical background
      of the special properties of stimuli-responsive hydrogels. Following, transducers
      are described which are able to convert the non-electrical changes of the
      physical properties of stimuli-responsive hydrogels into an electrical signal.
      Finally, the specific sensor properties, design rules and general conditions for
      sensor applications are discussed.

PMID- 27879723
TI  - Using Monoclonal Antibody to Determine Lead Ions with a Localized Surface Plasmon
      Resonance Fiber-optic Biosensor.
AB  - A novel reflection-based localized surface plasmon resonance (LSPR) fiber-optic
      probe has been developed to determine the heavy metal lead ion concentration.
      Monoclonal antibody as the detecting probe containing massive amino groups to
      capture Pb(II)-chelate complexes was immobilized onto gold nanoparticle-modified
      optical fiber (NMAuOF). The optimal immobilizing conditions of monoclonal
      antibody on to the NMAuOF are 189 MUg/mL in pH7.4 PBS for 2 h at 25 degrees C.
      The absorbability of the functionalized NMAuOF sensor increases to 12.2 % upon
      changing the Pb(II)-EDTA level from 10 to 100 ppb with a detection limit of 0.27
      ppb. The sensor retains 92.7 % of its original activity and gives reproducible
      results after storage in 5% D-( )-Trehalose dehydrate solution at 4 degrees C for
      35 days. In conclusion, the monoclonal antibody-functionalized NMAuOF sensor
      shows a promising result for determining the concentration of Pb(II) with high
      sensitivity.

PMID- 27879724
TI  - Optimalization of Poly(neutral red) Coated-wire Electrode for Determination of
      Citrate in Soft Drinks.
AB  - This report presents an optimization of potentiometric measurements withcitrate
      selective electropolymerized poly(neutral red) electrodes. The optimal
      backgroundelectrolyte for these measurements is a TRIS buffer with nitrate at pH
      8.5. The electrodesdescribed here exhibit stable and reproducible near-Nernstian
      response to citrates with alow detection limit of 6 * 10-6 M. Electrodes
      polymerized from sulfuric acid andacetonitrile are compared in detail. Simple and
      sensitive method for quantification ofcitrate in real-life samples by
      potentiometry with poly(neutral red) electrodes arepresented. Data from
      potentiometric measurements of citrate are compared with
      capillaryelectrophoresis.

PMID- 27879725
TI  - Using Geospatial Information Technology in Natural Resources Management: The Case
      of Urban Land Management In West Africa.
AB  - In the past several decades, Lagos Metropolis emerged as one of the
      fastesturbanizing cities in the West African Sub-region. In the absence of a
      regular use ofgeospatial information management systems, limited effort had been
      made to keep track ofchanges in the natural environment in the rapidly growing
      city for policy making in landadministration. The ubiquitous energy radiated by
      the rapid urbanization rate in the areanot only created unprecedented
      consequences by diminishing the quality of theenvironment and natural resources
      but it raises serious implications for land managementin the region. The factors
      fuelling the land crisis in the area which are not far fetchedconsists of socio
      economic, ecological and policy elements. To tackle these issues in amega city,
      up-to-date knowledge would be required to capture and analyze landinformation
      trends. Such an effort will help manage the city's expansion as well
      asinfrastructure development through the right choices in planning and (spatial)
      designsusing the latest tools in geospatial technologies of Geographic
      Information Systems GIS)and remote sensing. This study investigates the spatial
      implications of the rapid expansionof metropolitan Lagos for land management
      using GIS and Remote sensing technology.The result of the research provides a
      valuable road map that can enable planners contributeto improved land
      administration necessary for effective management of natural resources.

PMID- 27879726
TI  - Integration of Multiple Data Sources to Simulate the Dynamics of Land Systems.
AB  - In this paper we present and develop a new model, which we have calledDynamics of
      Land Systems (DLS). The DLS model is capable of integrating multiple datasources
      to simulate the dynamics of a land system. Three main modules are incorporatedin
      DLS: a spatial regression module, to explore the relationship between land uses
      andinfluencing factors, a scenario analysis module of the land uses of a region
      during thesimulation period and a spatial disaggregation module, to allocate land
      use changes froma regional level to disaggregated grid cells. A case study on
      Taips County in North Chinais incorporated in this paper to test the
      functionality of DLS. The simulation results underthe baseline, economic priority
      and environmental scenarios help to understand the landsystem dynamics and
      project near future land-use trajectories of a region, in order tofocus
      management decisions on land uses and land use planning.

PMID- 27879727
TI  - Vertex Separators for Partitioning a Graph.
AB  - Finite Element Method (FEM) is a well known technique extensively studiedfor
      spatial and temporal modeling of environmental processes, weather
      predictioncomputations, and intelligent signal processing for wireless sensors.
      The need for hugecomputational power arising in such applications to simulate
      physical phenomenoncorrectly mandates the use of massively parallel computers to
      distribute the workloadevenly. In this study, a novel heuristic algorithm called
      Line Graph Bisection whichpartitions a graph via vertex separators so as to
      balance the workload amongst theprocessors and to minimize the communication
      overhead is proposed. The proposedalgorithm is proved to be computationally
      feasible and makes cost-effective parallelimplementations possible to speed up
      the solution process.

PMID- 27879728
TI  - Monitoring and Predicting Land-use Changes and the Hydrology of the Urbanized
      Paochiao Watershed in Taiwan Using Remote Sensing Data, Urban Growth Models and a
      Hydrological Model.
AB  - Monitoring and simulating urban sprawl and its effects on land-use patterns
      andhydrological processes in urbanized watersheds are essential in land-use and
      waterresourceplanning and management. This study applies a novel framework to the
      urbangrowth model Slope, Land use, Excluded land, Urban extent, Transportation,
      andHillshading (SLEUTH) and land-use change with the Conversion of Land use and
      itsEffects (CLUE-s) model using historical SPOT images to predict urban sprawl in
      thePaochiao watershed in Taipei County, Taiwan. The historical and predicted land
      use datawas input into Patch Analyst to obtain landscape metrics. This data was
      also input to theGeneralized Watershed Loading Function (GWLF) model to analyze
      the effects of futureurban sprawl on the land-use patterns and watershed
      hydrology. The landscape metrics ofthe historical SPOT images show that land-use
      patterns changed between 1990-2000. TheSLEUTH model accurately simulated
      historical land-use patterns and urban sprawl in thePaochiao watershed, and
      simulated future clustered land-use patterns (2001-2025). TheCLUE-s model also
      simulated land-use patterns for the same period and yielded historical trends in
      the metrics of land-use patterns. The land-use patterns predicted by the
      SLEUTHand CLUE-s models show the significant impact urban sprawl will have on
      land-usepatterns in the Paochiao watershed. The historical and predicted land-use
      patterns in thewatershed tended to fragment, had regular shapes and interspersion
      patterns, but wererelatively less isolated in 2001-2025 and less interspersed
      from 2005-2025 compared withland-use pattern in 1990. During the study, the
      variability and magnitude of hydrologicalcomponents based on the historical and
      predicted land-use patterns were cumulativelyaffected by urban sprawl in the
      watershed; specifically, surface runoff increasedsignificantly by 22.0% and
      baseflow decreased by 18.0% during 1990-2025. The proposedapproach is an
      effective means of enhancing land-use monitoring and management ofurbanized
      watersheds.

PMID- 27879729
TI  - Analysis of Urban-Rural Land-Use Change during 1995-2006 and Its Policy
      Dimensional Driving Forces in Chongqing, China.
AB  - This paper analyzes the urban-rural land-use change of Chongqing and its
      policydimensional driving forces from 1995 to 2006, using high-resolution Landsat
      TM(Thematic Mapper) data of 1995, 2000 and 2006, and socio-economic data from
      bothresearch institutes and government departments. The outcomes indicated that
      urban-ruralland-use change in Chongqing can be characterized by two major trends:
      First, thenon-agricultural land increased substantially from 1995 to 2006, thus
      causing agriculturalland especially farmland to decrease continuously. Second,
      the aggregation index of urbansettlements and rural settlements shows that local
      urban-rural development experienced aprocess of changing from aggregation (1995
      2000) to decentralization (2000-2006).Chongqing is a special area getting
      immersed in many important policies, which includethe establishment of the
      municipality directly under the Central Government, the buildingof Three Gorges
      Dam Project, the Western China Development Program and theGrain-for-Green
      Programme, and bring about tremendous influences on its land-usechange. By
      analyzing Chongqing's land-use change and its policy driving forces,
      someimplications for its new policy of 'Urban-rural Integrated Reform' are
      obtained. That ismore attentions need to be paid to curbing excessive and idle
      rural housing andconsolidating rural construction land, and to laying out a
      scientific land-use plan for its rural areas taking such rural land-use issues as
      farmland occupation and rural housing landmanagement into accounts, so as to
      coordinate and balance the urban-rural development.

PMID- 27879730
TI  - Micro Fluidic Channel Machining on Fused Silica Glass Using Powder Blasting.
AB  - In this study, micro fluid channels are machined on fused silica glass via powder
      blasting, a mechanical etching process, and the machining characteristics of the
      channels are experimentally evaluated. In the process, material removal is
      performed by the collision of micro abrasives injected by highly compressed air
      on to the target surface. This approach can be characterized as an integration of
      brittle mode machining based on micro crack propagation. Fused silica glass, a
      high purity synthetic amorphous silicon dioxide, is selected as a workpiece
      material. It has a very low thermal expansion coefficient and excellent optical
      qualities and exceptional transmittance over a wide spectral range, especially in
      the ultraviolet range. The powder blasting process parameters affecting the
      machined results are injection pressure, abrasive particle size and density,
      stand-off distance, number of nozzle scanning, and shape/size of the required
      patterns. In this study, the influence of the number of nozzle scanning, abrasive
      particle size, and pattern size on the formation of micro channels is
      investigated. Machined shapes and surface roughness are measured using a 3
      dimensional vision profiler and the results are discussed.

PMID- 27879731
TI  - Evanescent field Sensors Based on Tantalum Pentoxide Waveguides - A Review.
AB  - Evanescent field sensors based on waveguide surfaces play an important rolewhere
      high sensitivity is required. Particularly tantalum pentoxide (Ta2O5) is a
      suitablematerial for thin-film waveguides due to its high refractive index and
      low attenuation.Many label-free biosensor systems such as grating couplers and
      interferometric sensors aswell as fluorescence-based systems benefit from this
      waveguide material leading toextremely high sensitivity. Some biosensor systems
      based on Ta2O5 waveguides alreadytook the step into commercialization. This
      report reviews the various detection systems interms of limit of detection, the
      applications, and the suitable surface chemistry.

PMID- 27879732
TI  - Electroanalysis of NADH Using Conducting and Redox Active Polymer/Carbon
      Nanotubes Modified Electrodes-A Review.
AB  - Past few decades, conducting and redox active polymers play a critical role in
      the development of transducers for biosensing. It has been evidenced by
      increasing numerous reports on conducting and redox active polymers incorporated
      electrodes for assay of biomolcules. This review highlights the potential uses of
      electrogenerated polymer modified electrodes and polymer/carbon nanotubes
      composite modified electrodes for electroanalysis of reduced form of nicotinamide
      adenine dinuceltoide (NADH). In addition, carbon electrodes modified with organic
      and inorganic materials as modifier have been discussed in detail for the
      quantification of NADH based on mediator or mediator-less methods.

PMID- 27879733
TI  - Experimental-Numerical Comparison of the Cantilever MEMS Frequency Shift in
      presence of a Residual Stress Gradient.
AB  - The dynamic characterization of a set of gold micro beams by electrostatic
      excitation in presence of residual stress gradient has been studied
      experimentally. A method to determine the micro-cantilever residual stress
      gradient by measuring the deflection and curvature and then identifying the
      residual stress model by means of frequency shift behaviour is presented. A
      comparison with different numerical FEM models and experimental results has been
      carried out, introducing in the model the residual stress of the structures,
      responsible for an initial upward curvature. Dynamic spectrum data are measured
      via optical interferometry and experimental frequency shift curves are obtained
      by increasing the dc voltage applied to the specimens. A good correspondence is
      pointed out between measures and numerical models so that the residual stress
      effect can be evaluated for different configurations.

PMID- 27879734
TI  - Suitability of MEMS Accelerometers for Condition Monitoring: An experimental
      study.
AB  - With increasing demands for wireless sensing nodes for assets control and
      condition monitoring; needs for alternatives to expensive conventional
      accelerometers in vibration measurements have been arisen. Micro-Electro
      Mechanical Systems (MEMS) accelerometer is one of the available options. The
      performances of three of the MEMS accelerometers from different manufacturers are
      investigated in this paper and compared to a well calibrated commercial
      accelerometer used as a reference for MEMS sensors performance evaluation. Tests
      were performed on a real CNC machine in a typical industrial environmental
      workshop and the achieved results are presented.

PMID- 27879735
TI  - An Automatic Instrument to Study the Spatial Scaling Behavior of Emissivity.
AB  - In this paper, the design of an automatic instrument for measuring the
      spatialdistribution of land surface emissivity is presented, which makes the
      direct in situmeasurement of the spatial distribution of emissivity possible. The
      significance of this newinstrument lies in two aspects. One is that it helps to
      investigate the spatial scalingbehavior of emissivity and temperature; the other
      is that, the design of the instrumentprovides theoretical and practical
      foundations for the implement of measuring distributionof surface emissivity on
      airborne or spaceborne. To improve the accuracy of themeasurements, the
      emissivity measurement and its uncertainty are examined in a series ofcarefully
      designed experiments. The impact of the variation of target temperature and
      theenvironmental irradiance on the measurement of emissivity is analyzed as well.
      Inaddition, the ideal temperature difference between hot environment and cool
      environmentis obtained based on numerical simulations. Finally, the scaling
      behavior of surfaceemissivity caused by the heterogeneity of target is discussed.

PMID- 27879736
TI  - Parallel Algorithm for GPU Processing; for use in High Speed Machine Vision
      Sensing of Cotton Lint Trash.
AB  - One of the main hurdles standing in the way of optimal cleaning of cotton lint
      isthe lack of sensing systems that can react fast enough to provide the control
      system withreal-time information as to the level of trash contamination of the
      cotton lint. This researchexamines the use of programmable graphic processing
      units (GPU) as an alternative to thePC's traditional use of the central
      processing unit (CPU). The use of the GPU, as analternative computation platform,
      allowed for the machine vision system to gain asignificant improvement in
      processing time. By improving the processing time, thisresearch seeks to address
      the lack of availability of rapid trash sensing systems and thusalleviate a
      situation in which the current systems view the cotton lint either well before,
      orafter, the cotton is cleaned. This extended lag/lead time that is currently
      imposed on thecotton trash cleaning control systems, is what is responsible for
      system operators utilizing avery large dead-band safety buffer in order to ensure
      that the cotton lint is not undercleaned.Unfortunately, the utilization of a
      large dead-band buffer results in the majority ofthe cotton lint being over
      cleaned which in turn causes lint fiber-damage as well assignificant losses of
      the valuable lint due to the excessive use of cleaning machinery. Thisresearch
      estimates that upwards of a 30% reduction in lint loss could be gained through
      theuse of a tightly coupled trash sensor to the cleaning machinery control
      systems. Thisresearch seeks to improve processing times through the development
      of a new algorithm forcotton trash sensing that allows for implementation on a
      highly parallel architecture.Additionally, by moving the new parallel algorithm
      onto an alternative computing platform,the graphic processing unit "GPU", for
      processing of the cotton trash images, a speed up ofover 6.5 times, over
      optimized code running on the PC's central processing unit "CPU", wasgained. The
      new parallel algorithm operating on the GPU was able to process a 1024x1024image
      in less than 17ms. At this improved speed, the image processing system's
      performance should now be sufficient to provide a system that would be capable of
      realtimefeed-back control that is in tight cooperation with the cleaning
      equipment.

PMID- 27879737
TI  - An Integrated GIS-Expert System Framework for Live Hazard Monitoring and
      Detection.
AB  - In the context of hazard monitoring, using sensor web technology to monitor
      anddetect hazardous conditions in near-real-time can result in large amounts of
      spatial data thatcan be used to drive analysis at an instrumented site. These
      data can be used for decisionmaking and problem solving, however as with any
      analysis problem the success ofanalyzing hazard potential is governed by many
      factors such as: the quality of the sensordata used as input; the meaning that
      can be derived from those data; the reliability of themodel used to describe the
      problem; the strength of the analysis methods; and the ability toeffectively
      communicate the end results of the analysis. For decision makers to make use
      ofsensor web data these issues must be dealt with to some degree. The work
      described in thispaper addresses all of these areas by showing how raw sensor
      data can be automaticallytransformed into a representation which matches a
      predefined model of the problem context.This model can be understood by analysis
      software that leverages rule-based logic andinference techniques to reason with,
      and draw conclusions about, spatial data. These toolsare integrated with a well
      known Geographic Information System (GIS) and existinggeospatial and sensor web
      infrastructure standards, providing expert users with the toolsneeded to
      thoroughly explore a problem site and investigate hazards in any domain.

PMID- 27879738
TI  - Pyridine Vapors Detection by an Optical Fibre Sensor.
AB  - An optical fibre sensor has been implemented towards pyridine vapors detection;to
      achieve this, a novel vapochromic material has been used, which, in solid state,
      suffers achange in colour from blue to pink-white in presence of pyridine
      vapours. This complex isadded to a solution of PVC (Poly Vinyl Chloride), TBP
      (Tributylphosphate) andtetrahydrofuran (THF), forming a plasticized matrix; by
      dip coating technique, the sensingmaterial is fixed onto a cleaved ended optical
      fibre. The fabrication process was optimizedin terms of number of dips and
      dipping speed, evaluating the final devices by dynamicrange. Employing a
      reflection set up, the absorbance spectra and changes in the reflectedoptical
      power of the sensors were registered to determine their response. A linear
      relationbetween optical power versus vapor concentration was obtained, with a
      detection limit of 1ppm (v/v).

PMID- 27879739
TI  - Ocean Color Inferred from Radiometers on Low-Flying Aircraft.
AB  - The color of sunlight reflected from the ocean to orbiting visible radiometers
      hasprovided a great deal of information about the global ocean, after suitable
      corrections aremade for atmospheric effects. Similar ocean-color measurements can
      be made from a lowflyingaircraft to get higher spatial resolution and to obtain
      measurements under clouds.A different set of corrections is required in this
      case, and we describe algorithms to correctfor clouds and sea-surface effects. An
      example is presented and errors in the correctionsdiscussed.

PMID- 27879740
TI  - Micro Dot Patterning on the Light Guide Panel Using Powder Blasting.
AB  - This study is to develop a micromachining technology for a light guidepanel(LGP)
      mold, whereby micro dot patterns are formed on a LGP surface by a singleinjection
      process instead of existing screen printing processes. The micro powder
      blastingtechnique is applied to form micro dot patterns on the LGP mold surface.
      The optimalconditions for masking, laminating, exposure, and developing processes
      to form the microdot patterns are first experimentally investigated. A LGP mold
      with masked micro patternsis then machined using the micro powder blasting method
      and the machinability of themicro dot patterns is verified. A prototype LGP is
      test- injected using the developed LGPmold and a shape analysis of the patterns
      and performance testing of the injected LGP arecarried out. As an additional
      approach, matte finishing, a special surface treatment method,is applied to the
      mold surface to improve the light diffusion characteristics, uniformity
      andbrightness of the LGP. The results of this study show that the applied powder
      blastingmethod can be successfully used to manufacture LGPs with micro patterns
      by just singleinjection using the developed mold and thereby replace existing
      screen printing methods.

PMID- 27879741
TI  - Metallic Nanomaterials for Sensitivity Enhancement of Fluorescence Detection.
AB  - Utrasensitive detection of trace analytes by fluorescence benefits
      forfluorescence amplifying substrates. We review here our recent work concerned
      withunderstanding of enhancement mechanisms and formation of three such
      substrates: silverfractals, silver coated gold nanoparticles deposited on glass
      and fluorescence enhancinggold colloids.

PMID- 27879742
TI  - Networked Estimation with an Area-Triggered Transmission Method.
AB  - This paper is concerned with the networked estimation problem in which sensordata
      are transmitted over the network. In the event-driven sampling scheme known
      aslevel-crossing or send-on-delta, sensor data are transmitted to the estimator
      node if thedifference between the current sensor value and the last transmitted
      one is greater than agiven threshold. The event-driven sampling generally
      requires less transmission than thetime-driven one. However, the transmission
      rate of the send-on-delta method becomeslarge when the sensor noise is large
      since sensor data variation becomes large due to thesensor noise. Motivated by
      this issue, we propose another event-driven sampling methodcalled area-triggered
      in which sensor data are sent only when the integral of differencesbetween the
      current sensor value and the last transmitted one is greater than a
      giventhreshold. Through theoretical analysis and simulation results, we show that
      in the certaincases the proposed method not only reduces data transmission rate
      but also improvesestimation performance in comparison with the conventional event
      driven method.

PMID- 27879743
TI  - Improving Distributed Runoff Prediction in Urbanized Catchments with Remote
      Sensing based Estimates of Impervious Surface Cover.
AB  - The amount and intensity of runoff on catchment scale are strongly determinedby
      the presence of impervious land-cover types, which are the predominant cover
      types inurbanized areas. This paper examines the impact of different methods for
      estimatingimpervious surface cover on the prediction of peak discharges, as
      determined by a fullydistributed rainfall-runoff model (WetSpa), for the upper
      part of the Woluwe Rivercatchment in the southeastern part of Brussels. The study
      shows that detailed informationon the spatial distribution of impervious
      surfaces, as obtained from remotely sensed data,produces substantially different
      estimates of peak discharges than traditional approachesbased on expert judgment
      of average imperviousness for different types of urban land use.The study also
      demonstrates that sub-pixel estimation of imperviousness may be a
      usefulalternative for more expensive high-resolution mapping for rainfall-runoff
      modelling atcatchment scale.

PMID- 27879744
TI  - Generalized Split-Window Algorithm for Estimate of Land Surface Temperature from
      Chinese Geostationary FengYun Meteorological Satellite (FY-2C) Data.
AB  - On the basis of the radiative transfer theory, this paper addressed the estimate
      ofLand Surface Temperature (LST) from the Chinese first operational
      geostationarymeteorological satellite-FengYun-2C (FY-2C) data in two thermal
      infrared channels (IR1,10.3-11.3 MU m and IR2, 11.5-12.5 MU m ), using the
      Generalized Split-Window (GSW)algorithm proposed by Wan and Dozier (1996). The
      coefficients in the GSW algorithmcorresponding to a series of overlapping ranging
      of the mean emissivity, the atmosphericWater Vapor Content (WVC), and the LST
      were derived using a statistical regressionmethod from the numerical values
      simulated with an accurate atmospheric radiativetransfer model MODTRAN 4 over a
      wide range of atmospheric and surface conditions.The simulation analysis showed
      that the LST could be estimated by the GSW algorithmwith the Root Mean Square
      Error (RMSE) less than 1 K for the sub-ranges with theViewing Zenith Angle (VZA)
      less than 30 degrees  or for the sub-rangs with VZA less than 60 degrees and the
      atmospheric WVC less than 3.5 g/cm2 provided that the Land Surface
      Emissivities(LSEs) are known. In order to determine the range for the optimum
      coefficients of theGSW algorithm, the LSEs could be derived from the data in
      MODIS channels 31 and 32 provided by MODIS/Terra LST product MOD11B1, or be
      estimated either according tothe land surface classification or using the method
      proposed by Jiang et al. (2006); and theWVC could be obtained from MODIS total
      precipitable water product MOD05, or beretrieved using Li et al.' method (2003).
      The sensitivity and error analyses in term of theuncertainty of the LSE and WVC
      as well as the instrumental noise were performed. Inaddition, in order to compare
      the different formulations of the split-window algorithms,several recently
      proposed split-window algorithms were used to estimate the LST with thesame
      simulated FY-2C data. The result of the intercomparsion showed that most of
      thealgorithms give comparable results.

PMID- 27879745
TI  - A Grain Flow Model to Simulate Grain Yield Sensor Response.
AB  - The objective of this study was to develop a flow model for grain combinesbased
      on the laboratory and field response of an impact based grain flow sensor. The
      grainflow model developed in this study is of first order with constant
      coefficients. A computercode was written to solve the model and to simulate the
      response of a yield sensor whoseresponse had been determined previously for
      various types of flow rate inputs both in fieldand laboratory experiments. The
      computer program for the simulation can alsocompensate for the time delay. The
      simulation results of the theoretical model suited wellto the experimental data
      and showed that the model effectively shows the input-outputrelationship of grain
      flow through a grain combine. This model could be used for periodicflow signals
      acquired from grain yield sensors. It was concluded that the model postulatedin
      this study could be further developed to determine the grain yield entering the
      combineusing the outlet flow rate measured by a yield sensor.

PMID- 27879746
TI  - Preliminary Results on Design and Implementation of a Solar Radiation Monitoring
      System.
AB  - The paper presents a solar radiation monitoring system, using two
      scientificpyranometers and an on-line computer home-made data acquisition system.
      The firstpyranometer measures the global solar radiation and the other one, which
      is shaded,measure the diffuse radiation. The values of total and diffuse solar
      radiation arecontinuously stored into a database on a server. Original software
      was created for dataacquisition and interrogation of the created system. The
      server application acquires the datafrom pyranometers and stores it into a
      database with a baud rate of one record at 50seconds. The client-server
      application queries the database and provides descriptivestatistics. A web
      interface allow to any user to define the including criteria and to obtainthe
      results. In terms of results, the system is able to provide direct, diffuse and
      totalradiation intensities as time series. Our client-server application computes
      also derivateheats. The ability of the system to evaluate the local solar energy
      potential is highlighted.

PMID- 27879747
TI  - Laboratory Evaluation of Acoustic Backscatter and LISST Methods for Measurements
      of Suspended Sediments.
AB  - The limitation of traditional sampling method to provide detailed spatial
      andtemporal profiles of suspended sediment concentration has led to an interest
      in alternativedevices and methods based on scattering of underwater sound and
      light . In the presentwork, acoustic backscatter and LISST (the Laser In Situ
      Scattering Transmissometry)devices, and methodologies were given. Besides a
      laboratory study was conducted tocompare pumping methods for different sediment
      radiuses at the same concentration. Theglass spheres (ballotini) of three
      different radiuses of 115, 137 and 163 MUm were used toobtain suspension in the
      sediment tower at laboratory. A quite good agreement wasobtained between these
      methods and pumping results with the range at 60.6-94.2% forsediment
      concentration and 91.3-100% for radius measurements. These results and theother
      studies show that these methods have potential for research tools for
      sedimentstudies. In addition further studies are needed to determine the ability
      of these methods forsediment measurement under different water and sediment
      material conditions.

PMID- 27879748
TI  - A Perturbation Method for the 3D Finite Element Modeling of Electrostatically
      Driven MEMS.
AB  - In this paper, a finite element (FE) procedure for modeling electrostatically
      actu-ated MEMS is presented. It concerns a perturbation method for computing
      electrostatic fielddistortions due to moving conductors. The computation is split
      in two steps. First, an un-perturbed problem (in the absence of certain
      conductors) is solved with the conventional FEmethod in the complete domain.
      Second, a perturbation problem is solved in a reduced re-gion with an additional
      conductor using the solution of the unperturbed problem as a source.When the
      perturbing region is close to the original source field, an iterative computation
      maybe required. The developed procedure offers the advantage of solving sub
      problems in re-duced domains and consequently of benefiting from different
      problem-adapted meshes. Thisapproach allows for computational efficiency by
      decreasing the size of the problem.

PMID- 27879750
TI  - LQER: A Link Quality Estimation based Routing for Wireless Sensor Networks.
AB  - Routing protocols are crucial to self-organize wireless sensor networks
      (WSNs),which have been widely studied in recent years. For some specific
      applications, both energyaware and reliable data transmission need to be
      considered together. Historical link statusshould be captured and taken into
      account in making data forwarding decisions to achievethe data reliability and
      energy efficiency tradeoff. In this paper, a dynamic window concept(m, k) is
      presented to record the link historical information and a link quality estimation
      basedrouting protocol (LQER) are proposed, which integrates the approach of
      minimum hop fieldand (m, k). The performance of LQER is evaluated by extensive
      simulation experiments to bemore energy-aware, with lower loss rate and better
      scalability than MHFR [1] and MCR [2].Thus the WSNs with LQER get longer lifetime
      of networks and better link quality.

PMID- 27879749
TI  - Selective Chemical Labeling of Proteins with Small Fluorescent Molecules Based on
      Metal-Chelation Methodology.
AB  - Site-specific chemical labeling utilizing small fluorescent molecules is
      apowerful and attractive technique for in vivo and in vitro analysis of cellular
      proteins,which can circumvent some problems in genetic encoding labeling by large
      fluorescentproteins. In particular, affinity labeling based on metal-chelation,
      advantageous due to thehigh selectivity/simplicity and the small tag-size, is
      promising, as well as enzymaticcovalent labeling, thereby a variety of novel
      methods have been studied in recent years.This review describes the advances in
      chemical labeling of proteins, especially highlightingthe metal-chelation
      methodology.

PMID- 27879752
TI  - Effects of van der Waals Force and Thermal Stresses on Pull-in Instability of
      Clamped Rectangular Microplates.
AB  - We study the influence of von Karman nonlinearity, van der Waals force, and a
      athermal stresses on pull-in instability and small vibrations of
      electrostatically actuated mi-croplates. We use the Galerkin method to develop a
      tractable reduced-order model for elec-trostatically actuated clamped rectangular
      microplates in the presence of van der Waals forcesand thermal stresses. More
      specifically, we reduce the governing two-dimensional nonlineartransient boundary
      value problem to a single nonlinear ordinary differential equation. For thestatic
      problem, the pull-in voltage and the pull-in displacement are determined by
      solving apair of nonlinear algebraic equations. The fundamental vibration
      frequency corresponding toa deflected configuration of the microplate is
      determined by solving a linear algebraic equa-tion. The proposed reduced-order
      model allows for accurately estimating the combined effectsof van der Waals force
      and thermal stresses on the pull-in voltage and the pull-in deflectionprofile
      with an extremely limited computational effort.

PMID- 27879751
TI  - Influence of Cadmium(II) Ions and Brewery Sludge on Metallothionein Level in
      Earthworms (Eisenia fetida) - Bio- transforming of Toxic Wastes.
AB  - Metallothioneins belong to a group of intracellular, high molecular andcysteine
      rich proteins whose content in an organism increase with increasing
      concentrationof a heavy metal. The aim of this work was to apply the
      electrochemical analysis for theanalysis of metallothioneins in earthworms
      exposed to cadmium ions and brewery sludge.Here we utilized adsorptive transfer
      technique coupled with differential pulse voltammetryBrdicka reaction to
      determine metallothionein in different biological samples. By meansthis very
      sensitive technique it was possible to analyze metallothionein in
      concentrationsbelow 1 MUmol.l-1 with the standard deviation of 4-5%. We found out
      that the average MTlevel in the non-treated earthworms oscillated between 19 and
      48 MUmol.l-1. When weanalysed samples of earthworms treated by cadmium, we
      observed that the MT contentincreased with the exposition length and increase
      dose of cadmium ions. Finally, weattempted to study and compare the toxicity of
      the raw sludge and its leach by using ofearthworms. The raw brewery sludge caused
      the death of the earthworms quickly.Earthworms held in the presence of leach from
      brewery sludge increased their weight of147 % of their original weight because
      they ingested the nutrients from the sludge. Themetallothionein level changes
      markedly with increasing time of exposition and applieddose of toxic compound. It
      clearly follows from the obtained results that the MT synthesisis insufficient in
      the first hours of the exposition and increases after more than 24 h.

PMID- 27879753
TI  - Integrating Remote Sensing Data with Directional Two- Dimensional Wavelet
      Analysis and Open Geospatial Techniques for Efficient Disaster Monitoring and
      Management.
AB  - In Taiwan, earthquakes have long been recognized as a major cause oflandslides
      that are wide spread by floods brought by typhoons followed.
      Distinguishingbetween landslide spatial patterns in different disturbance regimes
      is fundamental fordisaster monitoring, management, and land-cover restoration. To
      circumscribe landslides,this study adopts the normalized difference vegetation
      index (NDVI), which can bedetermined by simply applying mathematical operations
      of near-infrared and visible-redspectral data immediately after remotely sensed
      data is acquired. In real-time disastermonitoring, the NDVI is more effective
      than using land-cover classifications generatedfrom remotely sensed data as land
      cover classification tasks are extremely time consuming.Directional two
      dimensional (2D) wavelet analysis has an advantage over traditionalspectrum
      analysis in that it determines localized variations along a specific direction
      whenidentifying dominant modes of change, and where those modes are located in
      multi-temporal remotely sensed images. Open geospatial techniques comprise a
      series ofsolutions developed based on Open Geospatial Consortium specifications
      that can beapplied to encode data for interoperability and develop an open
      geospatial service for sharing data. This study presents a novel approach and
      framework that uses directional 2Dwavelet analysis of real-time NDVI images to
      effectively identify landslide patterns andshare resulting patterns via open
      geospatial techniques. As a case study, this study analyzedNDVI images derived
      from SPOT HRV images before and after the ChiChi earthquake(7.3 on the Richter
      scale) that hit the Chenyulan basin in Taiwan, as well as images aftertwo large
      typhoons (Xangsane and Toraji) to delineate the spatial patterns of
      landslidescaused by major disturbances. Disturbed spatial patterns of landslides
      that followed theseevents were successfully delineated using 2D wavelet analysis,
      and results of patternrecognitions of landslides were distributed simultaneously
      to other agents using geographymarkup language. Real-time information allows
      successive platforms (agents) to work withlocal geospatial data for disaster
      management. Furthermore, the proposed is suitable fordetecting landslides in
      various regions on continental, regional, and local scales usingremotely sensed
      data in various resolutions derived from SPOT HRV, IKONOS, andQuickBird
      multispectral images.

PMID- 27879754
TI  - Improvement of Aptamer Affinity by Dimerization.
AB  - To increase the affinities of aptamers for their targets, we designed an
      aptamerdimer for thrombin and VEGF. This design is based on the avidity of the
      antibody, whichenables the aptamer to connect easily since it is a single-strand
      nucleic acid. In this study,we connected a 15-mer thrombin-binding aptamer with a
      29-mer thrombin-binding aptamer.Each aptamer recognizes a different part of the
      thrombin molecule, and the aptamer dimerhas a Kd value which is 1/10 of that of
      the monomers from which it is composed. Also, thedesigned aptamer dimer has
      higher inhibitory activity than the reported (15-mer) thrombin-inhibiting
      aptamer. Additionally, we connected together two identical aptamers
      againstvascular endothelial growth factor (VEGF165), which is a homodimeric
      protein. As in thecase of the anti-thrombin aptamer, the dimeric anti-VEGF
      aptamer had a much lower Kd value than that of the monomer. This study
      demonstrated that the dimerization of aptamerseffectively improves the affinities
      of those aptamers for their targets.

PMID- 27879755
TI  - QoS Challenges and Opportunities in Wireless Sensor/Actuator Networks.
AB  - A wireless sensor/actuator network (WSAN) is a group of sensors and actuators
      that are geographically distributed and interconnected by wireless networks.
      Sensors gather information about the state of physical world. Actuators react to
      this information by performing appropriate actions. WSANs thus enable cyber
      systems to monitor and manipulate the behavior of the physical world. WSANs are
      growing at a tremendous pace, just like the exploding evolution of Internet.
      Supporting quality of service (QoS) will be of critical importance for pervasive
      WSANs that serve as the network infrastructure of diverse applications. To spark
      new research and development interests in this field, this paper examines and
      discusses the requirements, critical challenges, and open research issues on QoS
      management in WSANs. A brief overview of recent progress is given.

PMID- 27879756
TI  - Integrated Electrochemical Analysis System with Microfluidic and Sensing
      Functions.
AB  - An integrated device that carries out the timely transport of solutions
      andconducts electroanalysis was constructed. The transport of solutions was based
      oncapillary action in overall hydrophilic flow channels and control by valves
      that operateon the basis of electrowetting. Electrochemical sensors including
      glucose, lactate,glutamic oxaloacetic transaminase (GOT), glutamic pyruvic
      transaminase (GPT), pH,ammonia, urea, and creatinine were integrated. An air gap
      structure was used for theammonia, urea, and creatinine sensors to realize a
      rapid response. To enhance thetransport of ammonia that existed or was produced
      by the enzymatic reactions, the pHof the solution was elevated by mixing it with
      a NaOH solution using a valve based onelectrowetting. The sensors for GOT and GPT
      used a freeze-dried substrate matrix torealize rapid mixing. The sample solution
      was transported to required sensing sites atdesired times. The integrated sensors
      showed distinct responses when a sample solutionreached the respective sensing
      sites. Linear relationships were observed between theoutput signals and the
      concentration or the logarithm of the concentration of theanalytes. An
      interferent, L-ascorbic acid, could be eliminated electrochemically in thesample
      injection port.

PMID- 27879757
TI  - Comparison of Remote Sensing Image Processing Techniques to Identify Tornado
      Damage Areas from Landsat TM Data.
AB  - Remote sensing techniques have been shown effective for large-scale damagesurveys
      after a hazardous event in both near real-time or post-event analyses. The
      paperaims to compare accuracy of common imaging processing techniques to detect
      tornadodamage tracks from Landsat TM data. We employed the direct change
      detection approachusing two sets of images acquired before and after the tornado
      event to produce a principalcomponent composite images and a set of image
      difference bands. Techniques in thecomparison include supervised classification,
      unsupervised classification, and object-oriented classification approach with a
      nearest neighbor classifier. Accuracy assessment isbased on Kappa coefficient
      calculated from error matrices which cross tabulate correctlyidentified cells on
      the TM image and commission and omission errors in the result. Overall,the Object
      oriented Approach exhibits the highest degree of accuracy in tornado
      damagedetection. PCA and Image Differencing methods show comparable outcomes.
      Whileselected PCs can improve detection accuracy 5 to 10%, the Object-oriented
      Approachperforms significantly better with 15-20% higher accuracy than the other
      two techniques.

PMID- 27879758
TI  - Imaging In Mice With Fluorescent Proteins: From Macro To Subcellular.
AB  - Whole-body imaging with fluorescent proteins has been shown to be a
      powerfultechnology with many applications in small animals. Brighter, red-shifted
      proteins can makewhole-body imaging even more sensitive due to reduced absorption
      by tissues and less scatter.For example, a new protein called Katushka has been
      isolated that is the brightest known proteinwith emission at wavelengths longer
      than 620 nm. This new protein offers potential for non-invasive whole-body macro
      imaging such as of tumor growth. For subcellular imaging, toobserve cytoplasmic
      and nuclear dynamics in the living mouse, cancer cells were labeled in thenucleus
      with green fluorescent protein and with red fluorescent protein in the cytoplasm.
      Thenuclear and cytoplasmic behavior of cancer cells in real time in blood vessels
      was imaged as theytrafficked by various means or adhered to the vessel surface in
      the abdominal skin flap. Duringextravasation, real-time dual-color imaging showed
      that cytoplasmic processes of the cancer cellsexited the vessels first, with
      nuclei following along the cytoplasmic projections. Both cytoplasmand nuclei
      underwent deformation during extravasation. Cancer cells trafficking in
      lymphaticvessels was also imaged. To noninvasively image cancer cell/stromal cell
      interaction in the tumormicroenvironment as well as drug response at the cellular
      level in live animals in real time, wedeveloped a new imageable three-color
      animal model. The model consists of GFP-expressingmice transplanted with the dual
      color cancer cells. With the dual-color cancer cells and a highlysensitive small
      animal imaging system, subcellular dynamics can now be observed in live mice
      inreal time. Fluorescent proteins thus enable both macro and micro imaging
      technology and thereby provide the basis for the new field of in vivo cell
      biology.

PMID- 27879759
TI  - Temporal Stability of Soil Moisture and Radar Backscatter Observed by the
      Advanced Synthetic Aperture Radar (ASAR).
AB  - The high spatio-temporal variability of soil moisture is the result of
      atmosphericforcing and redistribution processes related to terrain, soil, and
      vegetation characteristics.Despite this high variability, many field studies have
      shown that in the temporal domainsoil moisture measured at specific locations is
      correlated to the mean soil moisture contentover an area. Since the measurements
      taken by Synthetic Aperture Radar (SAR)instruments are very sensitive to soil
      moisture it is hypothesized that the temporally stablesoil moisture patterns are
      reflected in the radar backscatter measurements. To verify this hypothesis 73
      Wide Swath (WS) images have been acquired by the ENVISAT AdvancedSynthetic
      Aperture Radar (ASAR) over the REMEDHUS soil moisture network located inthe Duero
      basin, Spain. It is found that a time-invariant linear relationship is well
      suited forrelating local scale (pixel) and regional scale (50 km) backscatter.
      The observed linearmodel coefficients can be estimated by considering the
      scattering properties of the terrainand vegetation and the soil moisture scaling
      properties. For both linear model coefficients,the relative error between
      observed and modelled values is less than 5 % and thecoefficient of determination
      (R2) is 86 %. The results are of relevance for interpreting anddownscaling coarse
      resolution soil moisture data retrieved from active (METOP ASCAT)and passive
      (SMOS, AMSR-E) instruments.

PMID- 27879760
TI  - Dependence of Impedance of Embedded Single Cells on Cellular Behaviour.
AB  - Non-invasive single cell analyses are increasingly required for the
      medicaldiagnostics of test substances or the development of drugs and therapies
      on the single celllevel. For the non-invasive characterisation of cells,
      impedance spectroscopy whichprovides the frequency dependent electrical
      properties has been used. Recently,microfludic systems have been investigated to
      manipulate the single cells and tocharacterise the electrical properties of
      embedded cells. In this article, the impedance ofpartially embedded single cells
      dependent on the cellular behaviour was investigated byusing the microcapillary.
      An analytical equation was derived to relate the impedance ofembedded cells with
      respect to the morphological and physiological change ofextracellular interface.
      The capillary system with impedance measurement showed afeasibility to monitor
      the impedance change of embedded single cells caused bymorphological and
      physiological change of cell during the addition of DMSO. By fittingthe derived
      equation to the measured impedance of cell embedded at different negativepressure
      levels, it was able to extrapolate the equivalent gap and gap conductivity
      betweenthe cell and capillary wall representing the cellular behaviour.

PMID- 27879761
TI  - An Auto-Recognizing System for Dice Games Using a Modified Unsupervised Grey
      Clustering Algorithm.
AB  - In this paper, a novel identification method based on a machine vision system is
      proposed to recognize the score of dice. The system employs image processing
      techniques, and the modified unsupervised grey clustering algorithm (MUGCA) to
      estimate the location of each die and identify the spot number accurately and
      effectively. The proposed algorithms are substituted for manual recognition. From
      the experimental results, it is found that this system is excellent due to its
      good capabilities which include flexibility, high speed, and high accuracy.

PMID- 27879762
TI  - Application of GeoWEPP for Determining Sediment Yield and Runoff in the Orcan
      Creek Watershed in Kahramanmaras, Turkey.
AB  - The geo-spatial interface of the WEPP model called GeoWEPP uses digital geo
      referenced information integrated with the most common GIS tools to predict
      sedimentyield and runoff. The model determines where and when the sediment yield
      and runoffoccurs and locates possible deposition places. In this study, the
      sediment yield and runofffrom Orcan Creek watershed in Kahramanmaras region was
      estimated by using GeoWEPPmodel. To investigate the performance of the model, the
      sediment yield and runoff resultsfrom the GeoWEPP model were compared with the
      observed monthly data collected fromthe sample watershed. The average Root Mean
      Square Errors (RMSE) between observedand predicted average annual sediment yield
      and runoff were 2.96 and 8.43, respectively.The index of agreement was 0.98 and
      0.99 for sediment yield and runoff, respectively,which indicated that the model
      predictions provided good results.

PMID- 27879763
TI  - Using ASTER Imagery in Land Use/cover Classification of Eastern Mediterranean
      Landscapes According to CORINE Land Cover Project.
AB  - The satellite imagery has been effectively utilized for classifying land
      covertypes and detecting land cover conditions. The Advanced Spaceborne Thermal
      Emissionand Reflection Radiometer (ASTER) sensor imagery has been widely used in
      classificationprocess of land cover. However, atmospheric corrections have to be
      made by preprocessingsatellite sensor imagery since the electromagnetic radiation
      signals received by the satellitesensors can be scattered and absorbed by the
      atmospheric gases and aerosols. In this study,an ASTER sensor imagery, which was
      converted into top-of-atmosphere reflectance(TOA), was used to classify the land
      use/cover types, according to COoRdination ofINformation on the Environment
      (CORINE) land cover nomenclature, for an arearepresenting the heterogonous
      characteristics of eastern Mediterranean regions inKahramanmaras, Turkey. The
      results indicated that using the surface reflectance data ofASTER sensor imagery
      can provide accurate (i.e. overall accuracy and kappa values of83.2% and 0.79,
      respectively) and low-cost cover mapping as a part of inventory forCORINE Land
      Cover Project.

PMID- 27879764
TI  - Techno-Economic Analysis of Solar Water Heating Systems inTurkey.
AB  - In this study, solar water heater was investigated using meteorological and
      geographical data of 129 sites over Turkey. Three different collector types were
      compared in terms of absorber material (copper, galvanized sheet and selective
      absorber). Energy requirement for water heating, collector performances, and
      economical indicators were calculated with formulations using observed data.
      Results showed that selective absorbers were most appropriate in terms of
      coverage rate of energy requirement for water-heating all over Turkey. The prices
      of selective, copper and galvanized absorber type's heating systems in Turkey
      were 740.49, 615.69 and 490.89 USD, respectively. While payback periods (PBPs) of
      the galvanized absorber were lower, net present values (NPVs) of the selective
      absorber were higher than the rest. Copper absorber type collectors did not
      appear to be appropriate based on economical indicators.

PMID- 27879765
TI  - Road Asphalt Pavements Analyzed by Airborne Thermal Remote Sensing: Preliminary
      Results of the Venice Highway.
AB  - This paper describes a fast procedure for evaluating asphalt pavement surface
      defects using airborne emissivity data. To develop this procedure, we used
      airborne multispectral emissivity data covering an urban test area close to
      Venice (Italy).For this study, we first identify and select the roads' asphalt
      pavements on Multispectral Infrared Visible Imaging Spectrometer (MIVIS) imagery
      using a segmentation procedure. Next, since in asphalt pavements the surface
      defects are strictly related to the decrease of oily components that cause an
      increase of the abundance of surfacing limestone, the diagnostic absorption
      emissivity peak at 11.2MUm of the limestone was used for retrieving from MIVIS
      emissivity data the areas exhibiting defects on asphalt pavements surface.The
      results showed that MIVIS emissivity allows establishing a threshold that points
      out those asphalt road sites on which a check for a maintenance intervention is
      required. Therefore, this technique can supply local government authorities an
      efficient, rapid and repeatable road mapping procedure providing the location of
      the asphalt pavements to be checked.

PMID- 27879767
TI  - Fabrication of Biochips with Micro Fluidic Channels by Micro End-milling and
      Powder Blasting.
AB  - For microfabrications of biochips with micro fluidic channels, a large number of
      microfabrication techniques based on silicon or glass-based Micro-Electro
      Mechanical System (MEMS) technologies were proposed in the last decade. In recent
      years, for low cost and mass production, polymer-based microfabrication
      techniques by microinjection molding and micro hot embossing have been proposed.
      These techniques, which require a proper photoresist, mask, UV light exposure,
      developing, and electroplating as a preprocess, are considered to have some
      problems. In this study, we propose a new microfabrication technology which
      consists of micro end-milling and powder blasting. This technique could be
      directly applied to fabricate the metal mold without any preprocesses. The metal
      mold with micro-channels is machined by micro end-milling, and then, burrs
      generated in the end-milling process are removed by powder blasting. From the
      experimental results, micro end-milling combined with powder blasting could be
      applied effectively for fabrication of the injection mold of biochips with micro
      fluidic channels.

PMID- 27879766
TI  - Construction of a nrdA::luxCDABE Fusion and Its Use in Escherichia coli as a DNA
      Damage Biosensor.
AB  - The promoter of nrdA gene which is related with DNA synthesis was used to
      construct a DNA damage sensitive biosensor. A recombinant bioluminescent E. coli
      strain, BBTNrdA, harboring a plasmid with the nrdA promoter fused to the luxCDABE
      operon, was successfully constructed. Its response to various chemicals including
      genotoxic chemicals substantiates it as a DNA damage biosensor. In
      characterization, three different classes of toxicants were used: DNA damaging
      chemicals, oxidative stress chemicals, and phenolics. BBTNrdA only responded
      strongly to DNA damaging chemicals, such as nalidixic acid (NDA), mitomycin C
      (MMC), 1-methyl-1-nitroso-N-methylguanidine (MNNG), and 4-nitroquinoline N-oxide
      (4-NQO). In contrast, there were no responses from the oxidative stress chemicals
      and phenolics, except from hydrogen peroxide (H2O2) which is known to cause DNA
      damage indirectly. Therefore, the results of the study demonstrate that BBTNrdA
      can be used as a DNA damage biosensor.

PMID- 27879768
TI  - The Successive Projection Algorithm (SPA), an Algorithm with a Spatial Constraint
      for the Automatic Search of Endmembers in Hyperspectral Data.
AB  - Spectral mixing is a problem inherent to remote sensing data and results in
      fewimage pixel spectra representing "pure" targets. Linear spectral mixture
      analysis isdesigned to address this problem and it assumes that the pixel-to
      pixel variability in ascene results from varying proportions of spectral
      endmembers. In this paper we present adifferent endmember-search algorithm called
      the Successive Projection Algorithm (SPA).SPA builds on convex geometry and
      orthogonal projection common to other endmembersearch algorithms by including a
      constraint on the spatial adjacency of endmembercandidate pixels. Consequently it
      can reduce the susceptibility to outlier pixels andgenerates realistic
      endmembers.This is demonstrated using two case studies (AVIRISCuprite cube and
      Probe-1 imagery for Baffin Island) where image endmembers can bevalidated with
      ground truth data. The SPA algorithm extracts endmembers fromhyperspectral data
      without having to reduce the data dimensionality. It uses the spectralangle
      (alike IEA) and the spatial adjacency of pixels in the image to constrain the
      selectionof candidate pixels representing an endmember. We designed SPA based on
      theobservation that many targets have spatial continuity (e.g. bedrock
      lithologies) in imageryand thus a spatial constraint would be beneficial in the
      endmember search. An additionalproduct of the SPA is data describing the change
      of the simplex volume ratio between successive iterations during the endmember
      extraction. It illustrates the influence of a newendmember on the data structure,
      and provides information on the convergence of thealgorithm. It can provide a
      general guideline to constrain the total number of endmembersin a search.

PMID- 27879769
TI  - Range and Velocity Estimation of Moving Targets Using Multiple Stepped-frequency
      Pulse Trains.
AB  - Range and velocity estimation of moving targets using conventional
      steppedfrequencypulse radar may suffer from the range-Doppler coupling and the
      phasewrapping. To overcome these problems, this paper presents a new radar
      waveform namedmultiple stepped-frequency pulse trains and proposes a new
      algorithm. It is shown that byusing multiple stepped-frequency pulse trains and
      the robust phase unwrapping theorem(RPUT), both of the range-Doppler coupling and
      the phase wrapping can be robustlyresolved, and accordingly, the range and the
      velocity of a moving target can be accuratelyestimated.

PMID- 27879770
TI  - Amperometric Enzyme-based Gas Sensor for Formaldehyde: Impact of Possible
      Interferences.
AB  - In this work, cross-sensitivities and environmental influences on the
      sensitivityand the functionality of an enzyme-based amperometric sensor system
      for the directdetection of formaldehyde from the gas phase are studied. The
      sensor shows a linearresponse curve for formaldehyde in the tested range (0 - 15
      vppm) with a sensitivity of1.9 MUA/ppm and a detection limit of about 130 ppb.
      Cross-sensitivities by environmentalgases like CO2, CO, NO, H2, and vapors of
      organic solvents like methanol and ethanol areevaluated as well as temperature
      and humidity influences on the sensor system. The sensorshowed neither
      significant signal to CO, H2, methanol or ethanol nor to variations in
      thehumidity of the test gas. As expected, temperature variations had the biggest
      influence onthe sensor sensitivity with variations in the sensor signal of up to
      10 % of the signal for 5vppm CH2O in the range of 25 - 30  degrees C.

PMID- 27879773
TI  - Topographic Effects on the Surface Emissivity of a Mountainous Area Observed by a
      Spaceborne Microwave Radiometer.
AB  - A simulation study to understand the influence of topography on the
      surfaceemissivity observed by a satellite microwave radiometer is carried out. We
      analyze theeffects due to changes in observation angle, including the rotation of
      the polarization plane.A mountainous area in the Alps (Northern Italy) is
      considered and the information on therelief extracted from a digital elevation
      model is exploited. The numerical simulation refersto a radiometric image,
      acquired by a conically-scanning radiometer similar to AMSR-E,i.e., flying at 705
      km of altitude with an observation angle of 55 degrees . To single out the
      impacton surface emissivity, scattering of the radiation due to the atmosphere or
      neighboringelevated surfaces is not considered. C and X bands, for which
      atmospheric effects arenegligible, and Ka band are analyzed. The results indicate
      that the changes in the localobservation angle tend to lower the apparent
      emissivity of a radiometric pixel with respectto the corresponding flat surface
      characteristics. The effect of the rotation of thepolarization plane enlarges
      (vertical polarization), or attenuates (horizontal polarization)this decrease. By
      doing some simplifying assumptions for the radiometer antenna, theconclusion is
      that the microwave emissivity at vertical polarization is underestimated,whilst
      the opposite occurs for horizontal polarization, except for Ka band, for which
      bothunder- and overprediction may occur. A quantification of the differences with
      respect to aflat soil and an approximate evaluation of their impact on soil
      moisture retrieval areyielded.

PMID- 27879774
TI  - Three-Dimensional Transport Modeling for Proton Exchange Membrane(PEM) Fuel Cell
      with Micro Parallel Flow Field.
AB  - Modeling and simulation for heat and mass transport in micro channel are
      beingused extensively in researches and industrial applications to gain better
      understanding of thefundamental processes and to optimize fuel cell designs
      before building a prototype forengineering application. In this study, we used a
      single-phase, fully three dimensionalsimulation model for PEMFC that can deal
      with both anode and cathode flow field forexamining the micro flow channel with
      electrochemical reaction. The results show thathydrogen and oxygen were solely
      supplied to the membrane by diffusion mechanism ratherthan convection transport,
      and the higher pressure drop at cathode side is thought to becaused by higher
      flow rate of oxygen at cathode. And it is found that the amount of water
      incathode channel was determined by water formation due to electrochemical
      reaction pluselectro-osmotic mass flux directing toward the cathode side. And it
      is very important tomodel the back diffusion and electro-osmotic mass flux
      accurately since the two flux wasclosely correlated each other and greatly
      influenced for determination of ionic conductivityof the membrane which directly
      affects the performance of fuel cell.

PMID- 27879771
TI  - Assembling Amperometric Biosensors for Clinical Diagnostics.
AB  - Clinical diagnosis and disease prevention routinely require the assessment
      ofspecies determined by chemical analysis. Biosensor technology offers several
      benefits overconventional diagnostic analysis. They include simplicity of use,
      specificity for the targetanalyte, speed to arise to a result, capability for
      continuous monitoring and multiplexing,together with the potentiality of coupling
      to low-cost, portable instrumentation. This workfocuses on the basic lines of
      decisions when designing electron-transfer-based biosensorsfor clinical analysis,
      with emphasis on the strategies currently used to improve the deviceperformance,
      the present status of amperometric electrodes for biomedicine, and the trendsand
      challenges envisaged for the near future.

PMID- 27879775
TI  - Application of Electrostatic Extrusion - Flavour Encapsulation and Controlled
      Release.
AB  - The subject of this study was the development of flavour alginate
      formulationsaimed for thermally processed foods. Ethyl vanilline was used as the
      model flavourcompound. Electrostatic extrusion was applied for the encapsulation
      of ethyl vanilline inalginate gel microbeads. The obtained microbeads with
      approx. 10 % w/w of ethylvanilline encapsulated in about 2 % w/w alginate were
      uniformly sized spheres of about450 MUm. Chemical characterization by H-NMR
      spectroscopy revealed that the alginateused in this study had a high content (67
      %) of guluronic residues and was rich in GG diadblocks (FGG = 55%) and thus
      presented a high-quality immobilisation matrix. The thermalbehaviour of alginate
      beads encapsulating ethyl vanilline was investigated bythermogravimetric (TG) and
      differential scanning calorimetry measurements (TG-DSC)under heating conditions
      which mimicked usual food processing to provide informationabout thermal
      decomposition of alginate matrix and kinetics of aroma release. Two wellresolved
      weight losses were observed. The first one was in the 50-150  degrees C
      temperaturerange with the maximum at approx. 112  degrees C, corresponding to the
      dehydration of thepolymer network. The second loss in the 220-325  degrees C
      temperature range, with a maximumat ~ 247  degrees C corresponded to the release
      of vanilline. The obtained results indicate that up to230  degrees C most of the
      vanilline remained intacta, while prolonged heating at elevatedtemperatures led
      to the entire loss of the aroma compound.

PMID- 27879776
TI  - Amperometric Low-Potential Detection of Malic Acid Using Single-Wall Carbon
      Nanotubes Based Electrodes.
AB  - The electrocatalytical property of single-wall carbon nanotube (SWNT)modified
      electrode toward NADH detection was explored by cyclic voltammetry andamperometry
      techniques. The experimental results show that SWNT decrease theovervoltage
      required for oxidation of NADH (to 300 mV vs. Ag/AgCl) and this propertymake them
      suitable for dehydrogenases based biosensors. The behavior of the SWNTmodified
      biosensor for L-malic acid was studied as an example for dehydrogenasesbiosensor.
      The amperometric measurements indicate that malate dehydrogenase (MDH)can be
      strongly adsorbed on the surface of the SWNT-modified electrode to form
      anapproximate monolayer film. Enzyme immobilization in Nafion membrane can
      increasethe biosensor stability. A linear calibration curve was obtained for L
      malic acidconcentrations between 0.2 and 1mM.

PMID- 27879777
TI  - Synthesis and Characterization of Carbon Nitride Films for Micro Humidity
      Sensors.
AB  - Nano-structured carbon nitride (CNx) films were synthesized by a reactive
      RFmagnetron sputtering system with a DC bias under various deposition conditions,
      and theirphysical and electrical properties were investigated with a view to
      using them for microhumidity sensors. The FTIR spectra of the deposited films
      showed a C=N stretching bandin the range of 1600~1700 ?-1, depending on the
      amount of nitrogen incorporation. Thecarbon nitride films deposited on the Si
      substrate had a nano-structured surfacemorphology with a grain size of about 20
      nm, and their deposition rate was 1.5 MUm/hr. Thesynthesized films had a high
      electrical resistivity in the range of 108 to 108 omega.cm,depending on the
      deposition conditions. The micro humidity sensors showed a goodlinearity and low
      hysteresis between 5 ~ 95 %RH.

PMID- 27879772
TI  - Electrochemical Biosensors - Sensor Principles and Architectures.
AB  - Quantification of biological or biochemical processes are of utmost importance
      for medical, biological and biotechnological applications. However, converting
      the biological information to an easily processed electronic signal is
      challenging due to the complexity of connecting an electronic device directly to
      a biological environment. Electrochemical biosensors provide an attractive means
      to analyze the content of a biological sample due to the direct conversion of a
      biological event to an electronic signal. Over the past decades several sensing
      concepts and related devices have been developed. In this review, the most common
      traditional techniques, such as cyclic voltammetry, chronoamperometry,
      chronopotentiometry, impedance spectroscopy, and various field-effect transistor
      based methods are presented along with selected promising novel approaches, such
      as nanowire or magnetic nanoparticle-based biosensing. Additional measurement
      techniques, which have been shown useful in combination with electrochemical
      detection, are also summarized, such as the electrochemical versions of surface
      plasmon resonance, optical waveguide lightmode spectroscopy, ellipsometry, quartz
      crystal microbalance, and scanning probe microscopy. The signal transduction and
      the general performance of electrochemical sensors are often determined by the
      surface architectures that connect the sensing element to the biological sample
      at the nanometer scale. The most common surface modification techniques, the
      various electrochemical transduction mechanisms, and the choice of the
      recognition receptor molecules all influence the ultimate sensitivity of the
      sensor. New nanotechnology-based approaches, such as the use of engineered ion
      channels in lipid bilayers, the encapsulation of enzymes into vesicles,
      polymersomes, or polyelectrolyte capsules provide additional possibilities for
      signal amplification. In particular, this review highlights the importance of the
      precise control over the delicate interplay between surface nano-architectures,
      surface functionalization and the chosen sensor transducer principle, as well as
      the usefulness of complementary characterization tools to interpret and to
      optimize the sensor response.

PMID- 27879778
TI  - The Application of DNA-Biosensors and Differential Scanning Calorimetry to the
      Study of the DNA-Binding Agent Berenil.
AB  - The in situ DNA-damaging capacity of berenil (1) has been investigated usingan
      electrochemical approach employing double stranded (ds) DNA-modified glassy
      carbonelectrode biosensors. Electrochemical voltammetric sensing of damage caused
      by 1 todsDNA was monitored by the appearance of peaks diagnostic of the oxidation
      of guanineand adenine. When 1 was incorporated directly onto the biosensor
      surface, DNA damagecould be observed at concentrations of additive as low as 10
      MUM. In contrast, when thedsDNA-modified biosensor was exposed to 1, in acetate
      buffer solution, the method wasmuch less sensitive and DNA damage could be
      detected only in the presence of 100 MUMberenil. When mixed solutions of 1 and
      single stranded (ss) DNA, polyguanylic acid orpolyadenylic acid were submitted to
      voltammetric study, the oxidation signals of therespective bases decreased in a
      concentration-dependent manner and the major variation ofthe adenine current peak
      indicated preferential binding of 1 to adenine. The electrochemical results were
      in close agreement with those deriving from a differentialscanning calorimetric
      study of the DNA-berenil complex.

PMID- 27879781
TI  - Low-cost Sensors Based on the GMI Effect in Recycled Transformer Cores.
AB  - Sensors based on the giant magnetoimpedance (GMI) effect in silicon steelswere
      constructed. Strips of silicon steels (0.500 mm-thick, 35.0 mm-long) with
      widthsranging from 0.122 to 1.064 mm were cut from recycled transformer cores.
      Since amaximum GMI ratio of 300% and a maximum field sensitivity of 1.5%/Oe were
      observedin a 1.064 mm-wide sample at 200 kHz, the 1.064 mm-wide strips were
      chosen as sensingelements in a slot key switch, angular velocity sensor, current
      sensor and force sensor. Thesensing elements were integrated into electronic
      circuits and the changes in impedancewere monitored. Variations in voltage due to
      these changes were typically small and musttherefore be amplified by the
      electronic circuits. For the current sensor and force sensor,the variation in the
      voltage drop across the GMI sensing element had non-linear variationswith either
      current or force and a conversion formula from a computer program wastherefore
      needed. The performance of the systems was tested. These sensing systems
      werestable, highly sensitive, hysteresis-free and could be produced on a mass
      scale. Based ontheir GMI effect, the silicon steels are versatile alternative low
      cost sensors.

PMID- 27879779
TI  - Transgenic Plants as Sensors of Environmental Pollution Genotoxicity.
AB  - Rapid technological development is inevitably associated with manyenvironmental
      problems which primarily include pollution of soil, water and air. In manycases,
      the presence of contamination is difficult to assess. It is even more difficult
      toevaluate its potential danger to the environment and humans. Despite the
      existence ofseveral whole organism-based and cell-based models of sensing
      pollution and evaluationof toxicity and mutagenicity, there is no ideal system
      that allows one to make a quick andcheap assessment. In this respect, transgenic
      organisms that can be intentionally altered tobe more sensitive to particular
      pollutants are especially promising. Transgenic plantsrepresent an ideal system,
      since they can be grown at the site of pollution or potentiallydangerous sites.
      Plants are ethically more acceptable and esthetically more appealing thananimals
      as sensors of environmental pollution. In this review, we will discuss
      varioustransgenic plant-based models that have been successfully used for
      biomonitoringgenotoxic pollutants. We will also discuss the benefits and
      potential drawbacks of thesesystems and describe some novel ideas for the future
      generation of efficient transgenicphytosensors.

PMID- 27879780
TI  - Ground Based Ultraviolet Remote Sensing of Volcanic Gas Plumes.
AB  - Ultraviolet spectroscopy has been implemented for over thirty years to
      monitorvolcanic SO2 emissions. These data have provided valuable information
      concerningunderground magmatic conditions, which have been of utility in eruption
      forecastingefforts. During the last decade the traditionally used correlation
      spectrometers have beenupgraded with miniature USB coupled UV spectrometers,
      opening a series of exciting newempirical possibilities for understanding
      volcanoes and their impacts upon the atmosphere.Here we review these
      technological developments, in addition to the scientific insightsthey have
      precipitated, covering the strengths and current limitations of this approach.

PMID- 27879782
TI  - An Artificial Neural Network Approach for the Prediction of Absorption
      Measurements of an Evanescent Field Fiber Sensor.
AB  - This paper describes artificial neural network (ANN) based prediction of
      theresponse of a fiber optic sensor using evanescent field absorption (EFA). The
      sensingprobe of the sensor is made up a bundle of five PCS fibers to maximize the
      interaction ofevanescent field with the absorbing medium. Different
      backpropagation algorithms areused to train the multilayer perceptron ANN. The
      Levenberg-Marquardt algorithm, aswell as the other algorithms used in this work
      successfully predicts the sensor responses.

PMID- 27879783
TI  - SU-8 Cantilevers for Bio/chemical Sensing; Fabrication, Characterisation and
      Development of Novel Read-out Methods.
AB  - Here, we present the activities within our research group over the last five
      yearswith cantilevers fabricated in the polymer SU-8. We believe that SU-8 is an
      interestingpolymer for fabrication of cantilevers for bio/chemical sensing due to
      its simple processingand low Young's modulus. We show examples of different
      integrated read-out methodsand their characterisation. We also show that SU-8
      cantilevers have a reduced sensitivity tochanges in the environmental temperature
      and pH of the buffer solution. Moreover, weshow that the SU-8 cantilever surface
      can be functionalised directly with receptormolecules for analyte detection,
      thereby avoiding gold-thiol chemistry.

PMID- 27879784
TI  - Object-based Land Cover Classification and Change Analysis in the Baltimore
      Metropolitan Area Using Multitemporal High Resolution Remote Sensing Data.
AB  - Accurate and timely information about land cover pattern and change in urbanareas
      is crucial for urban land management decision-making, ecosystem monitoring
      andurban planning. This paper presents the methods and results of an object
      basedclassification and post-classification change detection of multitemporal
      high-spatialresolution Emerge aerial imagery in the Gwynns Falls watershed from
      1999 to 2004. TheGwynns Falls watershed includes portions of Baltimore City and
      Baltimore County,Maryland, USA. An object-based approach was first applied to
      implement the land coverclassification separately for each of the two years. The
      overall accuracies of theclassification maps of 1999 and 2004 were 92.3% and
      93.7%, respectively. Following theclassification, we conducted a comparison of
      two different land cover change detectionmethods: traditional (i.e., pixel-based)
      post-classification comparison and object-basedpost-classification comparison.
      The results from our analyses indicated that an objectbasedapproach provides a
      better means for change detection than a pixel based methodbecause it provides an
      effective way to incorporate spatial information and expertknowledge into the
      change detection process. The overall accuracy of the change mapproduced by the
      object-based method was 90.0%, with Kappa statistic of 0.854, whereasthe overall
      accuracy and Kappa statistic of that by the pixel-based method were 81.3%
      and0.712, respectively.

PMID- 27879785
TI  - A Fluorescent Sensor for Dinitrobenzoic Acid Based on a Cyanuric Acid and
      Xanthene Skeleton.
AB  - A new fluorescent sensor based on a dimethylxanthene skeleton has
      beensynthesized. Because of its oxyanion hole structure, this receptor includes a
      suitablecavity for the association of carboxylic acids. The receptor's
      fluorescence is quenchedupon addition of dinitrobenzoic acid.

PMID- 27879787
TI  - Multiscale Unsupervised Segmentation of SAR Imagery Using the Genetic Algorithm.
AB  - A valid unsupervised and multiscale segmentation of synthetic aperture radar(SAR)
      imagery is proposed by a combination GA-EM of the Expectation Maximization(EM)
      algorith with the genetic algorithm (GA). The mixture multiscale
      autoregressive(MMAR) model is introduced to characterize and exploit the scale-to
      scale statisticalvariations and statistical variations in the same scale in SAR
      imagery due to radar speckle,and a segmentation method is given by combining the
      GA algorithm with the EMalgorithm. This algorithm is capable of selecting the
      number of components of the modelusing the minimum description length (MDL)
      criterion. Our approach benefits from theproperties of the Genetic and the EM
      algorithm by combination of both into a singleprocedure. The population-based
      stochastic search of the genetic algorithm (GA) exploresthe search space more
      thoroughly than the EM method. Therefore, our algorithm enablesescaping from
      local optimal solutions since the algorithm becomes less sensitive to
      itsinitialization. Some experiment results are given based on our proposed
      approach, andcompared to that of the EM algorithms. The experiments on the SAR
      images show that theGA-EM outperforms the EM method.

PMID- 27879786
TI  - Schiff's Bases and Crown Ethers as Supramolecular Sensing Materials in the
      Construction of Potentiometric Membrane Sensors.
AB  - Ionophore incorporated PVC membrane sensors are well-established analyticaltools
      routinely used for the selective and direct measurement of a wide variety of
      differentions in complex biological and environmental samples. Potentiometric
      sensors have someoutstanding advantages including simple design and operation,
      wide linear dynamic range,relatively fast response and rational selectivity. The
      vital component of such plasticizedPVC members is the ionophore involved,
      defining the selectivity of the electrodes' complexformation. Molecular
      recognition causes the formation of many different supramolecules.Different types
      of supramolecules, like calixarenes, cyclodextrins and podands, have beenused as
      a sensing material in the construction of ion selective sensors. Schiff's bases
      andcrown ethers, which feature prominently in supramolecular chemistry, can be
      used assensing materials in the construction of potentiometric ion selective
      electrodes. Up to now,more than 200 potentiometric membrane sensors for cations
      and anions based on Schiff's bases and crown ethers have been reported. In this
      review cation binding and anioncomplexes will be described. Liquid membrane
      sensors based on Schiff's bases and crownethers will then be discussed.

PMID- 27879789
TI  - Applications of the Integrated High-Performance CMOS Image Sensor to Range
      Finders - from Optical Triangulation to the Automotive Field.
AB  - With their significant features, the applications of complementary metal
      oxidesemiconductor (CMOS) image sensors covers a very extensive range, from
      industrialautomation to traffic applications such as aiming systems, blind
      guidance, active/passiverange finders, etc. In this paper CMOS image sensor-based
      active and passive rangefinders are presented. The measurement scheme of the
      proposed active/passive rangefinders is based on a simple triangulation method.
      The designed range finders chieflyconsist of a CMOS image sensor and some light
      sources such as lasers or LEDs. Theimplementation cost of our range finders is
      quite low. Image processing software to adjustthe exposure time (ET) of the CMOS
      image sensor to enhance the performance oftriangulation-based range finders was
      also developed. An extensive series of experimentswere conducted to evaluate the
      performance of the designed range finders. From theexperimental results, the
      distance measurement resolutions achieved by the active rangefinder and the
      passive range finder can be better than 0.6% and 0.25% within themeasurement
      ranges of 1 to 8 m and 5 to 45 m, respectively. Feasibility tests onapplications
      of the developed CMOS image sensor-based range finders to the automotivefield
      were also conducted. The experimental results demonstrated that our range finders
      arewell-suited for distance measurements in this field.

PMID- 27879788
TI  - Carbon Nanotubes Based Glucose Needle-type Biosensor.
AB  - A novel needle-type biosensor based on carbon nanotubes is reported. Thebiosensor
      was prepared by packing a mixture of multi-wall carbon nanotubes
      (MWCNTs),graphite powder and glucose oxidase (Gox) freeze-dried powder into a
      glass capillary of 0.5mm inner diameter. The resulting amperometric biosensor was
      characterizedelectrochemically using amperometry in the presence of hydrogen
      peroxide and in thepresence of glucose. The glucose biosensor sensitivity was
      influenced by the glucoseoxidase concentration within the MWCNTs mixture. The
      optimized glucose needle-typebiosensor displayed better sensitivity and
      stability, and a detected range of up to 20 mM.Based on its favorable stability,
      the needle biosensor was first time used in real-timemonitoring system as a kind
      of online glucose detector. The decay of current response isless than 10% after
      24-hour continuous observation.

PMID- 27879790
TI  - Assessing Steady-state Fluorescence and PRI from Hyperspectral Proximal Sensing
      as Early Indicators of Plant Stress: The Case of Ozone Exposure.
AB  - High spectral resolution spectrometers were used to detect optical signals
      ofongoing plant stress in potted white clover canopies subjected to ozone
      fumigation. Thecase of ozone stress is used in this manuscript as a paradigm of
      oxidative stress. Steadystatefluorescence (Fs) and the Photochemical Reflectance
      Index (PRI) were investigatedas advanced hyperspectral remote sensing techniques
      able to sense variations in the excessenergy dissipation pathways occurring when
      photosynthesis declines in plants exposed to astress agent. Fs and PRI were
      monitored in control and ozone fumigated canopies during a21-day experiment
      together with the traditional Normalized Difference Vegetation Index(NDVI) and
      physiological measurements commonly employed by physiologists to describestress
      development (i.e. net CO2 assimilation, active fluorimetry, chlorophyll
      concentrationand visible injuries). It is shown that remote detection of an
      ongoing stress through Fs andPRI can be achieved in an early phase, characterized
      by the decline of photosynthesis. Onthe contrary, NDVI was able to detect the
      stress only when damage occurred. These resultsopen up new possibilities for
      assessment of plant stress by means of hyperspectral remotesensing.

PMID- 27879791
TI  - An Open Distributed Architecture for Sensor Networks for Risk Management.
AB  - Sensors provide some of the basic input data for risk management of natural
      andman-made hazards. Here the word 'sensors' covers everything from remote
      sensingsatellites, providing invaluable images of large regions, through
      instruments installed on theEarth's surface to instruments situated in deep
      boreholes and on the sea floor, providinghighly-detailed point-based information
      from single sites. Data from such sensors is used inall stages of risk
      management, from hazard, vulnerability and risk assessment in the preeventphase,
      information to provide on-site help during the crisis phase through to data toaid
      in recovery following an event. Because data from sensors play such an important
      part inimproving understanding of the causes of risk and consequently in its
      mitigation,considerable investment has been made in the construction and
      maintenance of highlysophisticatedsensor networks. In spite of the ubiquitous
      need for information from sensornetworks, the use of such data is hampered in
      many ways. Firstly, information about thepresence and capabilities of sensor
      networks operating in a region is difficult to obtain dueto a lack of easily
      available and usable meta-information. Secondly, once sensor networkshave been
      identified their data it is often difficult to access due to a lack of
      interoperability between dissemination and acquisition systems. Thirdly, the
      transfer and processing ofinformation from sensors is limited, again by
      incompatibilities between systems. Therefore,the current situation leads to a
      lack of efficiency and limited use of the available data thathas an important
      role to play in risk mitigation. In view of this situation, the
      EuropeanCommission (EC) is funding a number of Integrated Projects within the
      Sixth FrameworkProgramme concerned with improving the accessibility of data and
      services for riskmanagement. Two of these projects: 'Open Architecture and
      Spatial Data Infrastructure forRisk Management' (ORCHESTRA, http://www.eu
      orchestra.org/) and 'Sensors Anywhere'(SANY, http://sany-ip.eu/) are discussed in
      this article. These projects have developed anopen distributed information
      technology architecture and have implemented web servicesfor the accessing and
      using data emanating, for example, from sensor networks. Thesedevelopments are
      based on existing data and service standards proposed by
      internationalorganizations. The projects seek to develop the ideals of the EC
      directive INSPIRE(http://inspire.jrc.it), which was launched in 2001 and whose
      implementation began this year(2007), into the risk management domain. Thanks to
      the open nature of the architecture andservices being developed within these
      projects, they can be implemented by any interestedparty and can be accessed by
      all potential users. The architecture is based around a serviceorientedapproach
      that makes use of Internet-based applications (web services) whose inputsand
      outputs conform to standards. The benefit of this philosophy is that it is
      expected tofavor the emergence of an operational market for risk management
      services in Europe, iteliminates the need to replace or radically alter the
      hundreds of already operational ITsystems in Europe (drastically lowering costs
      for users), and it allows users and stakeholdersto achieve interoperability while
      using the system most adequate to their needs, budgets,culture etc. (i.e. it has
      flexibility).

PMID- 27879792
TI  - Development and Demonstration of Measurement-Time Efficient Methods for Impedance
      Spectroscopy of Electrode and Sensor Arrays.
AB  - The development of impedance-based array devices is hindered by a lack ofrobust
      platforms and methods upon which to evaluate and interrogate sensors. One
      aspectto be addressed is the development of measurement-time efficient techniques
      forbroadband impedance spectroscopy of large electrode arrays. The objective of
      this workwas to substantially increase the low frequency impedance measurement
      throughputcapability of a large channel count array analyzer by developing true
      parallel measurementmethods. The goal was achieved by Fourier transform-based
      analysis of simultaneouslyacquiredmulti-channel time-based current and voltage
      data. Efficacy and quantitativeanalysis of the parallel approach at frequencies
      less than ca. 10 Hz as well as a combinedsequential parallel approach for
      efficient broadband impedance spectroscopy over 5-orders of magnitude in
      frequency is demonstrated through complex impedancemeasurement of arrays
      consisting of up to 100 elements.

PMID- 27879793
TI  - Localization Algorithm Based on a Spring Model (LASM) for Large Scale Wireless
      Sensor Networks.
AB  - A navigation method for a lunar rover based on large scale wireless
      sensornetworks is proposed. To obtain high navigation accuracy and large
      exploration area, highnode localization accuracy and large network scale are
      required. However, thecomputational and communication complexity and time
      consumption are greatly increasedwith the increase of the network scales. A
      localization algorithm based on a spring model(LASM) method is proposed to reduce
      the computational complexity, while maintainingthe localization accuracy in large
      scale sensor networks. The algorithm simulates thedynamics of physical spring
      system to estimate the positions of nodes. The sensor nodesare set as particles
      with masses and connected with neighbor nodes by virtual springs. Thevirtual
      springs will force the particles move to the original positions, the node
      positionscorrespondingly, from the randomly set positions. Therefore, a blind
      node position can bedetermined from the LASM algorithm by calculating the related
      forces with the neighbornodes. The computational and communication complexity are
      O(1) for each node, since thenumber of the neighbor nodes does not increase
      proportionally with the network scale size.Three patches are proposed to avoid
      local optimization, kick out bad nodes and deal withnode variation. Simulation
      results show that the computational and communicationcomplexity are almost
      constant despite of the increase of the network scale size. The time consumption
      has also been proven to remain almost constant since the calculation steps
      arealmost unrelated with the network scale size.

PMID- 27879794
TI  - A New PC and LabVIEW Package Based System for Electrochemical Investigations.
AB  - The paper describes a new PC and LabVIEW software package based system
      forelectrochemical research. An overview of well known electrochemical methods,
      such aspotential measurements, galvanostatic and potentiostatic method, cyclic
      voltammetry andEIS is given. Electrochemical impedance spectroscopy has been
      adapted for systemscontaining large capacitances. For signal generation and
      recording of the response ofinvestigated electrochemical cell, a measurement and
      control system was developed, basedon a PC P4. The rest of the hardware consists
      of a commercially available AD-DA converterand an external interface for analog
      signal processing. The interface is a result of authorsown research. The software
      platform for desired measurement methods is LabVIEW 8.2package, which is regarded
      as a high standard in the area of modern virtual instruments. Thedeveloped system
      was adjusted, tested and compared with commercially available systemand ORCAD
      simulation.

PMID- 27879795
TI  - Estimation of the Total Atmospheric Water Vapor Content and Land Surface
      Temperature Based on AATSR Thermal Data.
AB  - The total atmospheric water vapor content (TAWV) and land surfacetemperature
      (LST) play important roles in meteorology, hydrology, ecology and some
      otherdisciplines. In this paper, the ENVISAT/AATSR (The Advanced Along-Track
      ScanningRadiometer) thermal data are used to estimate the TAWV and LST over the
      Loess Plateauin China by using a practical split window algorithm. The
      distribution of the TAWV isaccord with that of the MODIS TAWV products, which
      indicates that the estimation of thetotal atmospheric water vapor content is
      reliable. Validations of the LST by comparingwith the ground measurements
      indicate that the maximum absolute derivation, themaximum relative error and the
      average relative error is 4.0K, 11.8% and 5.0%respectively, which shows that the
      retrievals are believable; this algorithm can provide anew way to estimate the
      LST from AATSR data.

PMID- 27879796
TI  - Amperometric Determination of Sulfite by Gas Diffusion- Sequential Injection with
      Boron-Doped Diamond Electrode.
AB  - A gas diffusion sequential injection system with amperometric detection using
      aboron-doped diamond electrode was developed for the determination of sulfite. A
      gasdiffusion unit (GDU) was used to prevent interference from sample matrices for
      theelectrochemical measurement. The sample was mixed with an acid solution to
      generategaseous sulfur dioxide prior to its passage through the donor channel of
      the GDU. Thesulfur dioxide diffused through the PTFE hydrophobic membrane into a
      carrier solution of 0.1 M phosphate buffer (pH 8)/0.1% sodium dodecyl sulfate in
      the acceptor channel of theGDU and turned to sulfite. Then the sulfite was
      carried to the electrochemical flow cell anddetected directly by amperometry
      using the boron-doped diamond electrode at 0.95 V(versus Ag/AgCl). Sodium dodecyl
      sulfate was added to the carrier solution to preventelectrode fouling. This
      method was applicable in the concentration range of 0.2-20 mgSO32-/L and a
      detection limit (S/N = 3) of 0.05 mg SO32-/L was achieved. This method
      wassuccessfully applied to the determination of sulfite in wines and the
      analytical resultsagreed well with those obtained by iodimetric titration. The
      relative standard deviations forthe analysis of sulfite in wines were in the
      range of 1.0-4.1 %. The sampling frequency was65 h-1.

PMID- 27879797
TI  - An Approach for Measuring the Sorptive Behavior of Odorants Using a Multifunction
      Thermal Desorber Unit: Preliminary Tests on Reduced Sulfur Compounds.
AB  - In this study, the sorptive behavior of reduced sulfur compounds (RSC) was
      investigated using a combination of thermal desorber (TD) unit and gas
      chromatography (GC). To examine the sorptive properties of RSC on textile
      materials, two types of experiments were conducted under experimental conditions
      favorable for sorptive processes. In all the experiments, gaseous standards of
      hydrogen sulfide, methanethiol, dimethyl sulfide, and dimethyl disulfide were
      supplied to initiate the adsorption processes on textile pieces. The textile
      pieces were then forced to release those adsorbed RSC under a fixed condition. It
      was found that the extent of adsorption, if evaluated quantitatively, occurred at
      approximately 1/1000 to 1/100 of the level of RSC standards supplied originally
      to induce adsorption. It also indicated that RSC adsorption was affected very
      sensitively by the initial exposure durations to induce RSC adsorption with an
      exponential decrease in relative recovery (RR) values with increasing exposure
      time. The relative sorptive patterns, when compared between different RSCs, were
      affected most sensitively by such factors as molecular weight and/or physical
      contact conditions.

PMID- 27879798
TI  - High Sensitive Temperature Sensor Using a Liquid-core Optical Fiber with Small
      Refractive Index Difference Between Core and Cladding Materials.
AB  - An intensive temperature sensor based on a liquid-core optical fiber has been
      demonstrated for the measuring the temperature of the environment. The core of
      fiber is filled with a mixture of toluene and chloroform in order to make the
      refractive index of the liquid-core and the cladding of the fiber close. The
      experiment shows that a temperature sensitivity of about 5 dB/K and a tunable
      temperature range (from 20 oC to 60 oC) can be achieved. Based on the dielectric
      clad liquid core fiber model, a simulation was carried out and the calculated
      results were in good accord with the experimental measurement.

PMID- 27879799
TI  - Sensitive Detection of Haloperidol and Hydroxyzine at Multi-Walled Carbon
      Nanotubes-Modified Glassy Carbon Electrodes.
AB  - Haloperidol (i.e. HPD) and hydroxyzine (i.e. HXY), two effective and important
      tranquilizers with low redox activity, were found to generate an irreversible
      anodic peak at about +0.86 V (vs. SCE) or two anodic peaks at about +0.83 and
      +0.91 V in 0.05 M NaH2PO4-Na2HPO4 (pH=7.0) buffer solution with a multi-walled
      carbon nanotubes-modified glassy carbon electrode (i.e. MWNTs/GC), respectively.
      Their sensitive and quantitative measurement based on the first two anodic peaks
      was established under the optimum conditions. The anodic peak current was linear
      to HPD and HXY concentration from 1*10-7 to 2.5 *10-5 M and 5*10-8 to 2.5 *10-5
      M, the detection limits obtained were 8*10-9 and 5*10-9 M, separately. The
      modified electrode exhibited some excellent characteristics including easy
      regeneration, high stability, good reproducibility and selectivity. The method
      proposed was successfully applied to the detection of HPD and HXY in drug tablets
      and proved to be reliable compared with ultraviolet spectrophotometry. The
      modified electrode was characterized by electrochemical methods.

PMID- 27879800
TI  - Electrochemical Determination of Trace Sudan I Contamination in Chili Powder at
      Carbon Nanotube Modified Electrodes.
AB  - We have developed a simple, convenient and inexpensive voltammetric method for
      determining trace Sudan I contamination in chili powder, based on the catalyzed
      electrochemical reduction of Sudan I at the carbon nanotube modified electrode.
      Under optimized conditions, the method exhibited acceptable analytical
      performance in terms of linearity (over the concentration range 6.0*10-7 to
      7.5*10-5 M, r = 0.9967), detection limit (2.0*10-7 M) and reproducibility (RSD =
      4.6%, n=10, for 2.0*10-5 M Sudan I).

PMID- 27879801
TI  - Sensor Performance Requirements for the Retrieval of Atmospheric Aerosols by
      Airborne Optical Remote Sensing.
AB  - This study explores performance requirements for the retrieval of the atmospheric
      aerosol optical depth (AOD) by airborne optical remote sensing instruments.
      Independent of any retrieval techniques, the calculated AOD retrieval
      requirements are compared with the expected performance parameters of the
      upcoming hyperspectral sensor APEX at the reference wavelength of 550nm. The AOD
      accuracy requirements are defined to be capable of resolving transmittance
      differences of 0.01 to 0.04 according to the demands of atmospheric corrections
      for remote sensing applications. For the purposes of this analysis, the signal at
      the sensor level is simulated by radiation transfer equations. The resulting
      radiances are translated into the AOD retrieval sensitivity (Deltataulambdaaer )
      and compared to the available measuring sensitivity of the sensor (NE
      DeltaLlambdasensor). This is done for multiple signal-to-noise ratios (SNR) and
      surface reflectance values. It is shown that an SNR of 100 is adequate for AOD
      retrieval at 550nm under typical remote sensing conditions and a surface
      reflectance of 10% or less. Such dark surfaces require the lowest SNR values and
      therefore offer the best sensitivity for measuring AOD. Brighter surfaces with up
      to 30% reflectance require an SNR of around 300. It is shown that AOD retrieval
      for targets above 50% surface reflectance is more problematic with the current
      sensor performance as it may require an SNR larger than 1000. In general,
      feasibility is proven for the analyzed cases under simulated conditions.

PMID- 27879802
TI  - A Dynamic Range Expansion Technique for CMOS Image Sensors with Dual Charge
      Storage in a Pixel and Multiple Sampling.
AB  - A dynamic range expansion technique for CMOS image sensors with dual charge
      storage in a pixel and multiple sampling technique is presented. Each pixel
      contains a photodiode and a storage diode which is connected to the photodiode
      via a separation gate. The sensitivity of the signal charge in the storage diode
      can be controlled either by a separation gate which limits the charge to flow
      into the storage diode or by controlling the accumulation time in the storage
      diode. The operation of the sensitivity control with separation gate techniques
      is simulated and it is found that a blocking layer to the storage diode plays an
      important role for high controllability of sensitivity of the storage diode. A
      prototype chip for testing multiple short time accumulations is fabricated and
      measured.

PMID- 27879803
TI  - Assessment and Analysis of QuikSCAT Vector Wind Products for the Gulf of Mexico:
      A Long-Term and Hurricane Analysis.
AB  - The northern Gulf of Mexico is a region that has been frequently impacted in
      recent years by natural disasters such as hurricanes. The use of remote sensing
      data such as winds from NASA's QuikSCAT satellite sensor would be useful for
      emergency preparedness during such events. In this study, the performance of
      QuikSCAT products, including JPL's latest Level 2B (L2B) 12.5 km swath winds,
      were evaluated with respect to buoy-measured winds in the Gulf of Mexico for the
      period January 2005 to February 2007. Regression analyses indicated better
      accuracy of QuikSCAT's L2B DIRTH, 12.5 km than the Level 3 (L3), 25 km wind
      product. QuikSCAT wind data were compared directly with buoy data keeping a
      maximum time interval of 20 min and spatial interval of 0.1 degrees  (~10 km). R2
      values for moderate wind speeds were 0.88 and 0.93 for L2B, and 0.75 and 0.89 for
      L3 for speed and direction, respectively. QuikSCAT wind comparisons for buoys
      located offshore were better than those located near the coast. Hurricanes that
      took place during 2002-06 were studied individually to obtain regressions of
      QuikSCAT versus buoys for those events. Results show QuikSCAT's L2B DIRTH wind
      product compared well with buoys during hurricanes up to the limit of buoy
      measurements. Comparisons with the National Hurricane Center (NHC) best track
      analyses indicated QuikSCAT winds to be lower than those obtained by NHC,
      possibly due to rain contamination, while buoy measurements appeared to be
      constrained at high wind speeds. This study has confirmed good agreement of the
      new QuikSCAT L2B product with buoy measurements and further suggests its
      potential use during extreme weather conditions in the Gulf of Mexico.

PMID- 27879804
TI  - Electrooxidation and Determination of Dopamine Using a Nafion(r)-Cobalt
      Hexacyanoferrate Film Modified Electrode.
AB  - The electrocatalysis of dopamine has been studied using a cobalt hexacyanoferrate
      film (CoHCFe)-modified glassy carbon electrode. Using a rotating disk CoHCFe
      modified electrode, the reaction rate constant for dopamine was found to be 3.5 *
      105 cm3 mol-1 s-1 at a concentration of 5.0 * 10-5 mol L-1. When a Nafion(r) film
      is applied to the CoHCFe-modified electrode surface a high selectivity for the
      determination of dopamine over ascorbic acid was obtained. The analytical curve
      for dopamine presented linear dependence over the concentration range from 1.2 *
      10-5 to 5.0 * 10-4 mol L-1 with a slope of 23.5 mA mol-1 L and a linear
      correlation coefficient of 0.999. The detection limit of this method was 8.9 * 10
      6 mol L-1 and the relative standard deviation for five measurements of 2.5 * 10-4
      mol L-1 dopamine was 0.58%.

PMID- 27879805
TI  - A Novel Optical Fiber Sensor for Steel Corrosion in Concrete Structures.
AB  - Steel corrosion resulting from the penetration of chloride ions or carbon dioxide
      is a major cause of degradation for reinforced concrete structures,. The
      objective of the present investigation was to develop a low-cost sensor for steel
      corrosion, which is based on a very simple physical principle. The flat end of a
      cut optical fiber is coated with an iron thin film using the ion sputtering
      technique. Light is then sent into a fiber embedded in concrete and the reflected
      signal is monitored. Initially, most of the light is reflected by the iron layer.
      When corrosion occurs to remove the iron layer, a significant portion of the
      light power will leave the fiber at its exposed end, and the reflected power is
      greatly reduced. Monitoring of the reflected signal is hence an effective way to
      assess if the concrete environment at the location of the fiber tip may induce
      steel corrosion or not. In this paper, first the principle of the corrosion
      sensor and its fabrication are described. The sensing principle is then verified
      by experimental results. Sensor packaging for practical installation will be
      presented and the performance of the packaged sensors is assessed by additional
      experiments.

PMID- 27879806
TI  - Hardware and Software of a Bipolar Current Source Controlled by PC.
AB  - This paper describes a realization of a bipolar current source developed by the
      paper's authors. The source is intended for use in galvanic and other industrial
      plants, where a pulse-reverse current supply (with the desired shape in time) is
      required. A prototype of the device, which provides the outcome current intensity
      up to +/- 50 A, has been constructed. The hardware of the source consists of a
      Pentium IV PC, a commercial ADDA converter, an interface of authors' original
      construction as well as a current regulator. The application software is
      developed using a commercial packet LabView as the basis.

PMID- 27879807
TI  - Innovative Sensors for Environmental Monitoring in Museums.
AB  - Different physical and chemical factors, such as light, temperature, relative
      humidity, pollutants and so on, can affect works of art on display. Each factor
      does not act individually, but its effect can be enhanced or accelerated by the
      presence of other factors. Accordingly, an evaluation of the impact of the whole
      environment on art objects is recognized as an essential requirement for
      conservation purposes. To meet the most up-todate guidelines on preventive
      conservation, in recent years several scientific projects supported by the EC
      were aimed at developing innovative tools that could complement the standard
      methods for environmental monitoring in museums. These research projects produced
      a new generation of passive sensors that are capable of taking into account the
      overall environmental effects by mimicking in some way the behaviour of real
      works of art. The main goal of the present paper is to provide a survey of these
      sensors, which represent a new frontier in the environmental control in museums.
      Furthermore, the use of optical fibres, as both intrinsic sensors and devices for
      interrogating sensors, will also be illustrated, and examples of their use in the
      cultural heritage field will be reported.

PMID- 27879808
TI  - Role of Satellite Sensors in Groundwater Exploration.
AB  - Spatial as well as spectral resolution has a very important role to play in water
      resource management. It was a challenge to explore the groundwater and rainwater
      harvesting sites in the Aravalli Quartzite-Granite-Pegmatite Precambrian terrain
      of Delhi, India. Use of only panchromatic sensor data of IRS-1D satellite with
      5.8-meter spatial resolution has the potential to infer lineaments and faults in
      this hard rock area. It is essential to identify the location of interconnected
      lineaments below buried pediment plains in the hard rock area for targeting sub
      surface water resources. Linear Image Self Scanning sensor data of the same
      satellite with 23.5-meter resolution when merged with the panchromatic data has
      produced very good results in delineation of interconnected lineaments over
      buried pediment plains as vegetation anomaly. These specific locations of
      vegetation anomaly were detected as dark red patches in various hard rock areas
      of Delhi. Field investigation was carried out on these patches by resistivity and
      magnetic survey in parts of Jawaharlal Nehru University (JNU), Indira Gandhi
      national Open University, Research and Referral Hospital and Humayuns Tomb areas.
      Drilling was carried out in four locations of JNU that proved to be the most
      potential site with ground water discharge ranging from 20,000 to 30,000 liters
      per hour with 2 to 4 meters draw down. Further the impact of urbanization on
      groundwater recharging in the terrain was studied by generating Normalized
      difference Vegetation Index (NDVI) map which was possible to generate by using
      the LISS-III sensor of IRS-1D satellite. Selection of suitable sensors has
      definitely a cutting edge on natural resource exploration and management
      including groundwater.

PMID- 27879809
TI  - Monitoring the Effects of Forest Restoration Treatments on Post-Fire Vegetation
      Recovery with MODIS Multitemporal Data.
AB  - This study examines how satellite based time-series vegetation greenness data and
      phenological measurements can be used to monitor and quantify vegetation recovery
      after wildfire disturbances and examine how pre-fire fuel reduction restoration
      treatments impact fire severity and impact vegetation recovery trajectories.
      Pairs of wildfire affected sites and a nearby unburned reference site were chosen
      to measure the post-disturbance recovery in relation to climate variation. All
      site pairs were chosen in forested uplands in Arizona and were restricted to the
      area of the Rodeo-Chediski fire that occurred in 2002. Fuel reduction treatments
      were performed in 1999 and 2001. The inter-annual and seasonal vegetation
      dynamics before, during, and after wildfire events can be monitored using a time
      series of biweekly composited MODIS NDVI (Moderate Resolution Imaging
      Spectroradiometer - Normalized Difference Vegetation Index) data. Time series
      analysis methods included difference metrics, smoothing filters, and fitting
      functions that were applied to extract seasonal and inter-annual change and
      phenological metrics from the NDVI time series data from 2000 to 2007. Pre- and
      post-fire Landsat data were used to compute the Normalized Burn Ratio (NBR) and
      examine burn severity at the selected sites. The phenological metrics (pheno
      metrics) included the timing and greenness (i.e. NDVI) for the start, peak and
      end of the growing season as well as proxy measures for the rate of green-up and
      senescence and the annual vegetation productivity. Pre-fire fuel reduction
      treatments resulted in lower fire severity, which reduced annual productivity
      much less than untreated areas within the Rodeo-Chediski fire perimeter. The
      seasonal metrics were shown to be useful for estimating the rate of post-fire
      disturbance recovery and the timing of phenological greenness phases. The use of
      satellite time series NDVI data and derived pheno-metrics show potential for
      tracking vegetation cover dynamics and successional changes in response to
      drought, wildfire disturbances, and forest restoration treatments in fire
      suppressed forests.

PMID- 27879811
TI  - An Optical Tomography System Using a Digital Signal Processor.
AB  - The use of a personal computer together with a Data Acquisition System (DAQ) as
      the processing tool in optical tomography systems has been the norm ever since
      the beginning of process tomography. However, advancements in silicon fabrication
      technology allow nowadays the fabrication of powerful Digital Signal Processors
      (DSP) at a reasonable cost. This allows this technology to be used in an optical
      tomography system since data acquisition and processing can be performed within
      the DSP. Thus, the dependency on a personal computer and a DAQ to sample and
      process the external signals can be reduced or even eliminated. The DSP system
      was customized to control the data acquisition process of 16x16 optical sensor
      array, arranged in parallel beam projection. The data collected was used to
      reconstruct the cross sectional image of the pipeline conveyor. For image display
      purposes, the reconstructed image was sent to a personal computer via serial
      communication. This allows the use of a laptop to display the tomogram image
      besides performing any other offline analysis.

PMID- 27879812
TI  - Mangrove Forest Distributions and Dynamics in Madagascar (1975-2005).
AB  - Mangrove forests of Madagascar are declining, albeit at a much slower rate than
      the global average. The forests are declining due to conversion to other land
      uses and forest degradation. However, accurate and reliable information on their
      present distribution and their rates, causes, and consequences of change have not
      been available. Earlier studies used remotely sensed data to map and, in some
      cases, to monitor mangrove forests at a local scale. Nonetheless, a comprehensive
      national assessment and synthesis was lacking. We interpreted time-series
      satellite data of 1975, 1990, 2000, and 2005 using a hybrid supervised and
      unsupervised classification approach. Landsat data were geometrically corrected
      to an accuracy of +/- one-half pixel, an accuracy necessary for change analysis.
      We used a postclassification change detection approach. Our results showed that
      Madagascar lost 7% of mangrove forests from 1975 to 2005, to a present extent of
      ~2,797 km2. Deforestation rates and causes varied both spatially and temporally.
      The forests increased by 5.6% (212 km2) from 1975 to 1990, decreased by 14.3%
      (455 km2) from 1990 to 2000, and decreased by 2.6% (73 km2) from 2000 to 2005.
      Similarly, major changes occurred in Bombekota Bay, Mahajamba Bay, the coast of
      Ambanja, the Tsiribihina River, and Cap St Vincent. The main factors responsible
      for mangrove deforestation include conversion to agriculture (35%), logging
      (16%), conversion to aquaculture (3%), and urban development (1%).

PMID- 27879813
TI  - Application of DNA Hybridization Biosensor as a Screening Method for the
      Detection of Genetically Modified Food Components.
AB  - An electrochemical biosensor for the detection of genetically modified food
      components is presented. The biosensor was based on 21-mer single-stranded
      oligonucleotide (ssDNA probe) specific to either 35S promoter or nos terminator,
      which are frequently present in transgenic DNA cassettes. ssDNA probe was
      covalently attached by 5'-phosphate end to amino group of cysteamine self
      assembled monolayer (SAM) on gold electrode surface with the use of activating
      reagents - water soluble 1-ethyl-3(3'- dimethylaminopropyl)-carbodiimide (EDC)
      and N-hydroxy-sulfosuccinimide (NHS). The hybridization reaction on the electrode
      surface was detected via methylene blue (MB) presenting higher affinity to ssDNA
      probe than to DNA duplex. The electrode modification procedure was optimized
      using 19-mer oligoG and oligoC nucleotides. The biosensor enabled distinction
      between DNA samples isolated from soybean RoundupReady(r) (RR soybean) and non
      genetically modified soybean. The frequent introduction of investigated DNA
      sequences in other genetically modified organisms (GMOs) give a broad
      perspectives for analytical application of the biosensor.

PMID- 27879810
TI  - Electrochemical Sensors for Clinic Analysis.
AB  - Demanded by modern medical diagnosis, advances in microfabrication technology
      have led to the development of fast, sensitive and selective electrochemical
      sensors for clinic analysis. This review addresses the principles behind
      electrochemical sensor design and fabrication, and introduces recent progress in
      the application of electrochemical sensors to analysis of clinical chemicals such
      as blood gases, electrolytes, metabolites, DNA and antibodies, including basic
      and applied research. Miniaturized commercial electrochemical biosensors will
      form the basis of inexpensive and easy to use devices for acquiring chemical
      information to bring sophisticated analytical capabilities to the non-specialist
      and general public alike in the future.

PMID- 27879814
TI  - Relationship Between Remotely-sensed Vegetation Indices, Canopy Attributes and
      Plant Physiological Processes: What Vegetation Indices Can and Cannot Tell Us
      About the Landscape.
AB  - Vegetation indices (VIs) are among the oldest tools in remote sensing studies.
      Although many variations exist, most of them ratio the reflection of light in the
      red and NIR sections of the spectrum to separate the landscape into water, soil,
      and vegetation. Theoretical analyses and field studies have shown that VIs are
      near-linearly related to photosynthetically active radiation absorbed by a plant
      canopy, and therefore to light-dependent physiological processes, such as
      photosynthesis, occurring in the upper canopy. Practical studies have used time
      series VIs to measure primary production and evapotranspiration, but these are
      limited in accuracy to that of the data used in ground truthing or calibrating
      the models used. VIs are also used to estimate a wide variety of other canopy
      attributes that are used in Soil-Vegetation-Atmosphere Transfer (SVAT), Surface
      Energy Balance (SEB), and Global Climate Models (GCM). These attributes include
      fractional vegetation cover, leaf area index, roughness lengths for turbulent
      transfer, emissivity and albedo. However, VIs often exhibit only moderate, non
      linear relationships to these canopy attributes, compromising the accuracy of the
      models. We use case studies to illustrate the use and misuse of VIs, and argue
      for using VIs most simply as a measurement of canopy light absorption rather than
      as a surrogate for detailed features of canopy architecture. Used this way, VIs
      are compatible with "Big Leaf" SVAT and GCMs that assume that canopy carbon and
      moisture fluxes have the same relative response to the environment as any single
      leaf, simplifying the task of modeling complex landscapes.

PMID- 27879815
TI  - Assessment of the Spatial Co-registration of Multitemporal Imagery from Large
      Format Digital Cameras in the Context of Detailed Change Detection.
AB  - Large format digital camera (LFDC) systems are becoming more broadly available
      and regularly collect image data over large areas. Spectral and radiometric
      attributes of imagery from LFDC systems make this type of image data appropriate
      for semi-automated change detection. However, achieving accurate spatial co
      registration between multitemporal image sets is necessary for semi-automated
      change detection. This study investigates the accuracy of co-registration between
      multitemporal image sets acquired using the Leica Geosystems ADS40, Intergraph
      Z/I Imaging(r) DMC, and Vexcel UltraCam-D sensors in areas of gentle, moderate,
      and extreme terrain relief. Custom image sets were collected and orthorectified
      by imagery vendors, with guidance from the authors. Results indicate that imagery
      acquired by vendors operating LFDC systems may be coregistered with pixel or sub
      pixel level accuracy, even for environments with high terrain relief. Specific
      image acquisition and processing procedures facilitating this level of
      coregistration are discussed.

PMID- 27879817
TI  - Identification of Metals (Heavy and Radioactive) in Drinking Water by an Indirect
      Analysis Method Based on Scale Tests.
AB  - The analysis of water quality, regarding the content of metals, especially heavy
      and radioactive ones, has been carried out in an indirect way, by testing scale
      formed in a hot-water heater, using water from the water-supply network of the
      city of Belgrade - the district of New Belgrade. The determination of the
      composition and the structure of the scale has resulted in its complete
      identification, and its crystallochemical formula has been defined. It has
      unequivocally been established that the obtained results are within the tolerance
      boundary with the results acquired by a conventional analysis of water, when it
      is a matter of very low concentrations. The presence of radioactive elements of
      uranium and strontium in a scale sample has been found and the way of their
      penetrating its composition and structure has been explained. Applying the
      fractional extraction method, uranium has been established to be of an
      anthropogenic origin.

PMID- 27879816
TI  - Assessment of Diaphragm and External Intercostals Fatigue from Surface EMG using
      Cervical Magnetic Stimulation.
AB  - This study was designed: (1) to test the reliability of surface electromyography
      (sEMG) recording of the diaphragm and external intercostals contractions response
      to cervical magnetic stimulation (CMS), (2) to examine the amount and the types
      of inspiratory muscle fatigue that developed after maximum voluntary ventilation
      (MVV) maneuvers.Ten male college students without physical disability (22.1+/-2.0
      years old) participated in the study and each completed a control (quiet
      breathing) trial and a fatigue (MVV maneuvers) trial sequentially. In the quiet
      breathing trial, the subjects maintained quiet breathing for five minutes. The
      subjects performed five maximal static inspiratory efforts and received five CMS
      before and after the quiet breathing. In the MVV trial, subjects performed five
      maximal inspiratory efforts and received five CMS before, immediately after, and
      ten minutes after two sets of MVV maneuvers performed five minutes apart. Maximal
      inspiratory pressure (PImax), sEMG of diaphragm and external intercostals during
      maximal static inspiratory efforts and during CMS were recorded. In the quiet
      breathing trial, high intraclass correlation coefficients (ICC=0.95-0.99) were
      observed in all the variables. In the MVV trial, the PImax, the EMG amplitude and
      the median power frequency during maximal static inspiratory efforts
      significantly decreased in both the diaphragm and the external intercostals
      immediately after the MVV maneuvers (P0.05). It is concluded that the sEMG
      recordings of the diaphragm during maximal static inspiratory efforts and in
      response to CMS allow reproducible sequential assessment of diaphragm
      contractility. MVV maneuvers resulted in inspiratory muscles fatigue, possibly
      central fatigue.

PMID- 27879818
TI  - Olfaction-based Detection Distance: A Quantitative Analysis of How Far Away Dogs
      Recognize Tortoise Odor and Follow It to Source.
AB  - The use of detector dogs has been demonstrated to be effective and safe for
      finding Mojave desert tortoises and provides certain advantages over humans in
      field surveys. Unlike humans who rely on visual cues for target identification,
      dogs use primarily olfactory cues and can therefore locate targets that are not
      visually obvious. One of the key benefits of surveying with dogs is their
      efficiency at covering ground and their ability to detect targets from long
      distances. Dogs may investigate potential targets using visual cues but confirm
      the presence of a target based on scent. Everything that emits odor does so via
      vapor-phase molecules and the components comprising a particular scent are
      carried primarily though bulk movement of the atmosphere. It is the ability to
      search for target odor and then go to its source that makes dogs ideal for rapid
      target recognition in the field setting. Using tortoises as targets, we
      quantified distances that dogs detected tortoise scent, followed it to source,
      and correctly identified tortoises as targets. Detection distance data were
      collected during experimental trials with advanced global positioning system
      (GPS) technology and then analyzed using geographic information system (GIS)
      modeling techniques. Detection distances ranged from 0.5 m to 62.8 m for
      tortoises on the surface. We did not observe bias with tortoise size, age class,
      sex or the degree to which tortoises were handled prior to being found by the
      dogs. The methodology we developed to quantify olfaction-based detection distance
      using dogs can be applied to other targets that dogs are trained to find.

PMID- 27879819
TI  - Rapid Urbanization and Implications for Flood Risk Management in Hinterland of
      the Pearl River Delta, China: The Foshan Study.
AB  - The purpose of this paper is to examine the linkage between rapid urbanization
      and flood risk in the hinterlands of the Pearl River Delta, P.R. China. Foshan, a
      typical hinterland city in the Pearl River Delta region, was selected as a case
      study. Land use and cover change in Foshan during 1988-2003 was analyzed using
      remote sensing and geographic information system (GIS) techniques. Furthermore,
      analysis on historical hydrological data during 1962-2005 was performed. Results
      show that rapid urbanization has resulted in losses of farmland, forest and shrub
      since 1988. In addition, in order to compensate or offset the loss of farmland
      due to rapid urban expansion, more than 30 % of the forest and 20 % of the shrub
      areas were transformed into farmlands. Inevitably, both the urban and
      agricultural lands increased the pressure on the drainage systems. Furthermore,
      over the past decades human activities such as dredging up the floodways,
      excavating sand and building water facilities in the rivers, significantly
      changed the hydrological conditions, and therefore impaired the rivers' capacity
      to buffer floods. Lessons from the Foshan case implied that, in addition to
      natural processes, human activities driven by socio-economic factors should be
      considered responsible for the recently increasing level of flood risks. Both
      economically and environmentally, it is irrational and impractical to encourage
      encroachment of lands vulnerable to floods. It is also realistic and urgent to
      effectively prevent and control the adverse ecological consequences of
      urbanization and economic activities for building their wealth and prominence.

PMID- 27879820
TI  - Error and Performance Analysis of MEMS-based Inertial Sensors with a Low-cost GPS
      Receiver.
AB  - Global Navigation Satellite Systems (GNSS), such as the Global Positioning System
      (GPS), have been widely utilized and their applications are becoming popular, not
      only in military or commercial applications, but also for everyday life. Although
      GPS measurements are the essential information for currently developed land
      vehicle navigation systems (LVNS), GPS signals are often unavailable or
      unreliable due to signal blockages under certain environments such as urban
      canyons. This situation must be compensated in order to provide continuous
      navigation solutions. To overcome the problems of unavailability and
      unreliability using GPS and to be cost and size effective as well, Micro Electro
      Mechanical Systems (MEMS) based inertial sensor technology has been pushing for
      the development of low-cost integrated navigation systems for land vehicle
      navigation and guidance applications. This paper will analyze the
      characterization of MEMS based inertial sensors and the performance of an
      integrated system prototype of MEMS based inertial sensors, a low-cost GPS
      receiver and a digital compass. The influence of the stochastic variation of
      sensors will be assessed and modeled by two different methods, namely Gauss
      Markov (GM) and AutoRegressive (AR) models, with GPS signal blockage of different
      lengths. Numerical results from kinematic testing have been used to assess the
      performance of different modeling schemes.

PMID- 27879821
TI  - Airborne Laser Scanning Quantification of Disturbances from Hurricanes and
      Lightning Strikes to Mangrove Forests in Everglades National Park, USA.
AB  - Airborne light detection and ranging (LIDAR) measurements derived before and
      after Hurricanes Katrina and Wilma (2005) were used to quantify the impact of
      hurricanes and lightning strikes on the mangrove forest at two sites in
      Everglades National Park (ENP). Analysis of LIDAR measurements covering 61 and 68
      ha areas of mangrove forest at the Shark River and Broad River sites showed that
      the proportion of high tree canopy detected by the LIDAR after the 2005 hurricane
      season decreased significantly due to defoliation and breakage of branches and
      trunks, while the proportion of low canopy and the ground increased drastically.
      Tall mangrove forests distant from tidal creeks suffered more damage than lower
      mangrove forests adjacent to the tidal creeks. The hurricanes created numerous
      canopy gaps, and the number of gaps per square kilometer increased from about
      400~500 to 4000 after Katrina and Wilma. The total area of gaps in the forest
      increased from about 1~2% of the total forest area to 12%. The relative
      contribution of hurricanes to mangrove forest disturbance in ENP is at least 2
      times more than that from lightning strikes. However, hurricanes and lightning
      strikes disturb the mangrove forest in a related way. Most seedlings in lightning
      gaps survived the hurricane impact due to the protection of trees surrounding the
      gaps, and therefore provide an important resource for forest recovery after the
      hurricane. This research demonstrated that LIDAR is an effective remote sensing
      tool to quantify the effects of disturbances such as hurricanes and lightning
      strikes in the mangrove forest.

PMID- 27879822
TI  - An Electrochemical Detection of Metallothioneins at the Zeptomole Level in
      Nanolitre Volumes.
AB  - An Electrochemical Detection of Metallothioneins at the Zeptomole Level in
      Nanolitre VolumesWe report on improvement of the adsorptive transfer stripping
      technique (AdTS) coupled with the differential pulse voltammetry Brdicka reaction
      to determine a thiol-protein. The current technique has been unable to generate
      reproducible results when analyzing very low sample volumes (nanolitres). This
      obstacle can be overcome technically by modifying the current transfer technique
      including cooling step of the adsorbed analyte. We tested the technique on
      determination of a promising tumour disease marker protein called metallothionein
      (MT). The detection limit (3 S/N) of MT was evaluated as 500 zeptomoles per 500
      nL (1 pM) and the quantification limit (10 S/N) as 1,500 zeptomoles per 500 nL (3
      pM). Further, the improved AdTS technique was utilized to analyze blood serum
      samples from patients with breast cancer. Based on the results obtained it can be
      concluded that the improved technique can be used to detect a thiolprotein in
      very low sample volumes and can also prevent interferences during the washing and
      transferring step.

PMID- 27879823
TI  - Compound Cellular Imaging of Laser Scanning Confocal Microscopy by Using Gold
      Nanoparticles and Dyes.
AB  - Combining the scattered light of gold nanoparticles (GNPs) and the fluorescence
      of dye molecules, a compound cellular imaging of laser scanning confocal
      microscopy (LSCM) is obtained. The human breast cancer cell line (MDA-MB-435S,
      BCRC 60429) is used for experiment. These cells are incubated with a glucose
      medium containing GNPs for 26 hours, and then are stained by Prodium Iodide (PI)
      for their nuclei. By using a single laser to illuminate these cells and adjusting
      the ranges of two bandpass filters for the detection, the scattered light from
      the GNPs and the fluorescence of PI can be induced simultaneously, but be
      detected separately without crosstalk. Furthermore, a compound cellular image can
      be obtained by merging the two images of the expressions of GNP and PI together.
      From the TEM images of these cells, it is observed that GNPs are aggregated in
      the vesicles of the cytoplasm due to the cell's endocytosis. The aggregation of
      GNPs makes the surface plasmon resonance band of GNPs broadened, so that strong
      scattered light from GNPs can be generated by the illumination of different
      wavelength lasers (458, 488, 514, 561, and 633 nm).

PMID- 27879824
TI  - A Micromachined Capacitive Pressure Sensor Using a Cavity-Less Structure with
      Bulk-Metal/Elastomer Layers and Its Wireless Telemetry Application.
AB  - This paper reports a micromachined capacitive pressure sensor intended for
      applications that require mechanical robustness. The device is constructed with
      two micromachined metal plates and an intermediate polymer layer that is soft
      enough to deform in a target pressure range. The plates are formed of
      micromachined stainless steel fabricated by batch-compatible micro-electro
      discharge machining. A polyurethane roomtemperature- vulcanizing liquid rubber of
      38-MUm thickness is used as the deformable material. This structure eliminates
      both the vacuum cavity and the associated lead transfer challenges common to
      micromachined capacitive pressure sensors. For frequency-based interrogation of
      the capacitance, passive inductor-capacitor tanks are fabricated by combining the
      capacitive sensor with an inductive coil. The coil has 40 turns of a 127
      MUmdiameter copper wire. Wireless sensing is demonstrated in liquid by monitoring
      the variation in the resonant frequency of the tank via an external coil that is
      magnetically coupled with the tank. The sensitivity at room temperature is
      measured to be 23-33 ppm/KPa over a dynamic range of 340 KPa, which is shown to
      match a theoretical estimation. Temperature dependence of the tank is
      experimentally evaluated.

PMID- 27879826
TI  - Heavy Metal Concentrations in Soils and Factors Affecting Metal Uptake by Plants
      in the Vicinity of a Korean Cu-W Mine.
AB  - Heavy metal concentrations were measured in soils and plants in and around a
      copper-tungsten mine in southeast Korea to investigate the influence of past base
      metal mining on the surface environment. The results of chemical analysis
      indicate that the heavy metals in soils decreased with distance from the source,
      controlled mainly by water movement and topography. The metal concentrations
      measured in plant species generally decreased in the order; spring onions >
      soybean leaves > perilla leaves " red pepper > corn grains " jujube grains,
      although this pattern varied moderately between different elements. The results
      agree with other reports that metal concentrations in leaves are usually much
      higher than those in grain. Factors influencing the bioavailability of metals and
      their occurrences in crops were found as soil pH, cation exchange capacity,
      organic matter content, soil texture, and interaction among the target elements.
      It is concluded that total metal concentrations in soils are the main controls on
      their contents in plants. Soil pH was also an important factor. A stepwise linear
      multiple regression analysis was also conducted to identify the dominant factors
      influencing metal uptake by plants. Metal concentrations in plants were also
      estimated by computer-aided statistical methods.

PMID- 27879827
TI  - Personalization of Rule-based Web Services.
AB  - Nowadays Web users have clearly expressed their wishes to receive personalized
      services directly. Personalization is the way to tailor services directly to the
      immediate requirements of the user. However, the current Web Services System does
      not provide any features supporting this such as consideration of personalization
      of services and intelligent matchmaking. In this research a flexible,
      personalized Rule-based Web Services System to address these problems and to
      enable efficient search, discovery and construction across general Web documents
      and Semantic Web documents in a Web Services System is proposed. This system
      utilizes matchmaking among service requesters', service providers' and users'
      preferences using a Rule-based Search Method, and subsequently ranks search
      results. A prototype of efficient Web Services search and construction for the
      suggested system is developed based on the current work.

PMID- 27879828
TI  - Systems and Sensors for Debris-flow Monitoring and Warning.
AB  - Debris flows are a type of mass movement that occurs in mountain torrents. They
      consist of a high concentration of solid material in water that flows as a wave
      with a steep front. Debris flows can be considered a phenomenon intermediate
      between landslides and water floods. They are amongst the most hazardous natural
      processes in mountainous regions and may occur under different climatic
      conditions. Their destructiveness is due to different factors: their capability
      of transporting and depositing huge amounts of solid materials, which may also
      reach large sizes (boulders of several cubic meters are commonly transported by
      debris flows), their steep fronts, which may reach several meters of height and
      also their high velocities. The implementation of both structural and
      nonstructural control measures is often required when debris flows endanger
      routes, urban areas and other infrastructures. Sensor networks for debris-flow
      monitoring and warning play an important role amongst non-structural measures
      intended to reduce debris-flow risk. In particular, debris flow warning systems
      can be subdivided into two main classes: advance warning and event warning
      systems. These two classes employ different types of sensors. Advance warning
      systems are based on monitoring causative hydrometeorological processes
      (typically rainfall) and aim to issue a warning before a possible debris flow is
      triggered. Event warning systems are based on detecting debris flows when these
      processes are in progress. They have a much smaller lead time than advance
      warning ones but are also less prone to false alarms. Advance warning for debris
      flows employs sensors and techniques typical of meteorology and hydrology,
      including measuring rainfall by means of rain gauges and weather radar and
      monitoring water discharge in headwater streams. Event warning systems use
      different types of sensors, encompassing ultrasonic or radar gauges, ground
      vibration sensors, videocameras, avalanche pendulums, photocells, trip wires etc.
      Event warning systems for debris flows have a strong linkage with debris-flow
      monitoring that is carried out for research purposes: the same sensors are often
      used for both monitoring and warning, although warning systems have higher
      requirements of robustness than monitoring systems. The paper presents a
      description of the sensors employed for debris-flow monitoring and event warning
      systems, with attention given to advantages and drawbacks of different types of
      sensors.

PMID- 27879829
TI  - Absorbance Based Light Emitting Diode Optical Sensors and Sensing Devices.
AB  - The ever increasing demand for in situ monitoring of health, environment and
      security has created a need for reliable, miniaturised sensing devices. To
      achieve this, appropriate analytical devices are required that possess operating
      characteristics of reliability, low power consumption, low cost, autonomous
      operation capability and compatibility with wireless communications systems. The
      use of light emitting diodes (LEDs) as light sources is one strategy, which has
      been successfully applied in chemical sensing. This paper summarises the
      development and advancement of LED based chemical sensors and sensing devices in
      terms of their configuration and application, with the focus on transmittance and
      reflectance absorptiometric measurements.

PMID- 27879830
TI  - Inter-Comparison of ASTER and MODIS Surface Reflectance and Vegetation Index
      Products for Synergistic Applications to Natural Resource Monitoring.
AB  - Synergistic applications of multi-resolution satellite data have been of a great
      interest among user communities for the development of an improved and more
      effective operational monitoring system of natural resources, including
      vegetation and soil. In this study, we conducted an inter-comparison of two
      remote sensing products, namely, visible/near-infrared surface reflectances and
      spectral vegetation indices (VIs), from the high resolution Advanced Thermal
      Emission and Reflection Radiometer (ASTER) (15 m) and lower resolution Moderate
      Resolution Imaging Spectroradiometer (MODIS) (250 m - 500 m) sensors onboard the
      Terra platform. Our analysis was aimed at understanding the degree of radiometric
      compatibility between the two sensors' products due to sensor spectral bandpasses
      and product generation algorithms. Multiple pairs of ASTER and MODIS standard
      surface reflectance products were obtained at randomly-selected, globally
      distributed locations, from which two types of VIs were computed: the normalized
      difference vegetation index and the enhanced vegetation indices with and without
      a blue band. Our results showed that these surface reflectance products and the
      derived VIs compared well between the two sensors at a global scale, but subject
      to systematic differences, of which magnitudes varied among scene pairs. An
      independent assessment of the accuracy of ASTER and MODIS standard products, in
      which "in-house" surface reflectances were obtained using in situ Aeronet
      atmospheric data for comparison, suggested that the performance of the ASTER
      atmospheric correction algorithm may be variable, reducing overall quality of its
      standard reflectance product. Atmospheric aerosols, which were not corrected for
      in the ASTER algorithm, were found not to impact the quality of the derived
      reflectances. Further investigation is needed to identify the sources of
      inconsistent atmospheric correction results associated with the ASTER algorithm,
      including additional quality assessments of the ASTER and MODIS products with
      other atmospheric radiative transfer codes.

PMID- 27879825
TI  - Developments in the Field of Conducting and Non-conducting Polymer Based
      Potentiometric Membrane Sensors for Ions Over the Past Decade.
AB  - Many research studies have been conducted on the use of conjugated polymers in
      the construction of chemical sensors including potentiometric, conductometric and
      amperometric sensors or biosensors over the last decade. The induction of
      conductivity on conjugated polymers by treating them with suitable oxidizing
      agents won Heeger, MacDiarmid and Shirakawa the 2000 Nobel Prize in Chemistry.
      Common conjugated polymers are poly(acetylene)s, poly(pyrrole)s,
      poly(thiophene)s, poly(terthiophene)s, poly(aniline)s, poly(fluorine)s, poly(3
      alkylthiophene)s, polytetrathiafulvalenes, polynapthalenes, poly(p-phenylene
      sulfide), poly(p-phenylenevinylene)s, poly(3,4-ethylenedioxythiophene),
      polyparaphenylene, polyazulene, polyparaphenylene sulfide, polycarbazole and
      polydiaminonaphthalene. More than 60 sensors for inorganic cations and anions
      with different characteristics based on conducting polymers have been reported.
      There have also been reports on the application of non-conducting polymers
      (nCPs), i.e. PVC, in the construction of potentiometric membrane sensors for
      determination of more than 60 inorganic cations and anions. However, the leakage
      of ionophores from the membranes based on these polymers leads to relatively
      lower life times. In this article, we try to give an overview of Solid-Contact
      ISE (SCISE), Single-Piece ISE (SPISE), Conducting Polymer (CP)-Based, and also
      non-conducting polymer PVC-based ISEs for various ions which their difference is
      in the way of the polymer used with selective membrane. In SCISEs and SPISEs, the
      plasticized PVC containing the ionophore and ionic additives govern the
      selectivity behavior of the electrode and the conducting polymer is responsible
      of ion-to-electron transducer. However, in CPISEs, the conducting polymer layer
      is doped with a suitable ionophore which enhances the ion selectivity of the CP
      while its redox response has to be suppressed.

PMID- 27879831
TI  - Improving Empirical Mode Decomposition Using Support Vector Machines for
      Multifocus Image Fusion.
AB  - Empirical mode decomposition (EMD) is good at analyzing nonstationary and
      nonlinear signals while support vector machines (SVMs) are widely used for
      classification. In this paper, a combination of EMD and SVM is proposed as an
      improved method for fusing multifocus images. Experimental results show that the
      proposed method is superior to the fusion methods based on a-trous wavelet
      transform (AWT) and EMD in terms of quantitative analyses by Root Mean Squared
      Error (RMSE) and Mutual Information (MI).

PMID- 27879832
TI  - Estimation of Stand Type Parameters and Land Cover Using Landsat-7 ETM Image: A
      Case Study from Turkey.
AB  - Remote sensing has been considered a low-cost, large-area coverage forest
      information resource ideally suited to broad-scale forest inventory objectives.
      The objective of this study is to determine stand type parameters such as crown
      closure, development stage and stand types, and land cover obtained from Landsat
      7 ETM image and forest cover type map (stand type map). The research also focuses
      on classifying and mapping the stand parameters with the spatial analysis
      functions of GIS. In the study, stand parameters determined by forest cover type
      map and remote sensing methods were compared and contrasted to evaluate the
      potential use of the remote sensing methods. The result showed that development
      stage were estimated with Landsat 7 ETM image using supervised classification
      with a 0.89 kappa statistic value and 92% overall accuracy assessments. Among the
      features, development stages were the most successfully classified stand
      parameters in classification process. According to the spatial accuracy
      assessment results, development stages also had the highest accuracy of 72.2%. As
      can be seen in the results, spatial accuracy is lower than classification
      accuracy. Stand type had the lowest accuracy of 32.8. In conclusion, it could be
      stated that development stages, crown closure and land cover could be determined
      at an acceptable level using Landsat 7 ETM image. However, Landsat 7 ETM image do
      not provide means to map and monitor minor vegetation communities and stand types
      at stand level due to low spatial resolution. High resolution satellite images
      could be used either alone or with field survey data.

PMID- 27879833
TI  - Classifying Oriental Beech (Fagus orientalis Lipsky.) Forest Sites Using Direct,
      Indirect and Remote Sensing Methods: A Case Study from Turkey.
AB  - Determining the productivity of forest sites through various classification
      techniques is important for making appropriate forest management decisions.
      Forest sites were classified using direct and indirect (site index) and remote
      sensing (Landsat 7 ETM and Quickbird satellite image) methods. In the direct
      method, forest site classifications were assigned according to edafic (soil
      properties), climate (precipitation and temperature) and topographic (altitude,
      slope, aspect and landform) factors. Five different forest site classes (dry,
      moderate fresh, fresh, moist and highly moist) were determined. In the indirect
      method, the guiding curve was used to generate anamorphic site index (SI)
      equations resulting in three classes; good (SI=I-II), medium (SI=III) and poor
      (SI=IV-V). Forest sites were also determined with a remote sensing method (RSM)
      using supervised classification of Landsat 7 ETM and Quickbird satellite images
      with a 0.67 kappa statistic value and 73.3% accuracy assessments; 0.88 kappa
      statistic value and 90.7% accuracy assessments, respectively. Forest sites
      polygon themes obtained from the three methods were overlaid and areas in the
      same classes were computed with Geographic Information Systems (GIS). The results
      indicated that direct and SI methods were consistent as a 3% dry site (19.0 ha)
      was exactly determined by both the direct and SI methods as a site class IV.
      Comparison of SI and RMS methods indicated a small difference as the area was
      highly homogeneous and unmanaged. While 15.4 ha area (open and degraded areas)
      was not determined by SI but RSM. A 19.0 ha (100%) poor site was determined by
      the SI method, 14.9 ha (78%) poor site was in Landsat 7 ETM satellite image and
      17.4 ha (92%) poor site in Quickbird satellite image. The relationship between
      direct and SI methods were statistically analyzed using chi-square test. The test
      indicated a statistically significant relationships between forest sites
      determined by direct method and Quicbird satellite image (chi2 = 36.794; df = 16;
      p = 0.002), but no significant relationships with Landsat 7 ETM satellite image
      (chi2 = 22.291; df = 16; p = 0.134). Moderate association was found between SI
      method and direct method (chi2 = 16.724; df = 8; p = 0.033).

PMID- 27879834
TI  - Analyzing the Variation of Building Density Using High Spatial Resolution
      Satellite Images: the Example of Shanghai City.
AB  - Building density is an important issue in urban planning and land management. In
      the article, building coverage ratio (BCR) and floor area ratio (FAR) values
      extracted from high resolution satellite images were used to indicate buildings'
      stretching on the surface and growth along the third dimension within areas of
      interest in Shanghai City, P.R. China. The results show that the variation of FAR
      is higher than that of BCR in the inner circle, and that the newer commercial
      centers have higher FAR and lower BCR values, while the traditional commercial
      areas have higher FAR and BCR ratios. By comparing different residential areas,
      it was found that the historical "Shikumen" areas and the old residential areas
      built before 1980s have higher BCR and lower FAR, while the new residential areas
      have higher FAR and lower BCR, except for the villa areas. These results suggest
      that both older building areas and villa areas use land resources in an
      inefficient way, and therefore better planning and management of urban land are
      needed for those fast economic growing regions.

PMID- 27879835
TI  - A Special Fiber Optic Sensor for Measuring Wheel Loads of Vehicles on Highways.
AB  - This paper presents results from an investigation on a special optical fiber as a
      load sensor for application in Weigh-in-Motion (WIM) systems to measure wheel
      loads of vehicles traveling at normal speed on highways. The fiber used has a
      unique design with two concentric light guiding regions of different effective
      optical path lengths, which has the potential to enable direct measurement of
      magnitudes as well as locations of forces acting at multiple points along a
      single fiber. The optical characteristic of the fiber for intended sensing
      purpose was first assessed by a simple fiber bending experiment and by
      correlating the bend radii with the output light signal intensities. A simple
      laboratory load transmitting/fiber bending device was then designed and
      fabricated to appropriately bend the optical fiber under applied loads in order
      to make the fiber work as load sensor. The device with the optical fiber was
      tested under a universal loading machine and an actual vehicle wheel in the
      laboratory. The test results showed a good relationship between the magnitude of
      the applied load and the output optical signal changes. The results also showed a
      good correlation between the time delay between the inner and outer core light
      pulses and the distance of the applied load as measured from the output end of
      the fiber.

PMID- 27879836
TI  - Conductometric Microbiosensors for Environmental Monitoring.
AB  - This review presents the principles of conductometric measurements in ionic media
      and the equivalent electrical circuits of different designs for conductometric
      measurements. These types of measurements were first applied for monitoring
      biocatalytic reactions. The use of conductometric microtransducers is then
      presented and detailed in the case of pollutant detection for environmental
      monitoring. Conductometric biosensors have advantages over other types of
      transducers: they can be produced through inexpensive thinfilm standard
      technology, no reference electrode is needed and differential mode measurements
      allow cancellation of a lot of interferences. The specifications obtained for the
      detection of different pesticides, herbicides and heavy metal ions, based on
      enzyme inhibition, are presented as well as those obtained for the detection of
      formaldehyde, 4- chlorophenol, nitrate and proteins as markers of dissolved
      organic carbon based on enzymatic microbiosensors.

PMID- 27879837
TI  - Biomarkers of Contaminant Exposure in Chub (Leuciscus cephalus L.) -
      Biomonitoring of Major Rivers in the Czech Republic.
AB  - Biochemical analysis of organisms to assess exposure to environmental
      contaminants is of great potential use. Biochemical markers, specifically liver
      enzymes of the first and the second phase of xenobiotic transformation -
      cytochrome P450 (CYP 450), ethoxyresorufin-O-deethylase (EROD), glutathione-S
      transferase (GST) and tripeptide reduced glutathione (GSH) - were used to assess
      contamination of the aquatic environment at 12 locations near the mouths of major
      rivers in the Czech Republic. These rivers were the Luznice, Otava, Sazava,
      Berounka, Vltava, Labe, Ohre, Svratka, Dyje, Morava and Odra. The indicator
      species selected was the Chub (Leuciscus cephalus L.). The highest levels of CYP
      450 and EROD catalytic activity were found in livers of fish from the Labe
      (Obristvi) (0.32+/-0.10 nmol mg-1 protein and 1061.38+/-545.51 pmol min-1 mg-1
      protein, respectively). The highest levels of GST catalytic activity and GSH
      content were found in fish from the Otava (35.39+/-13.35 nmol min-1 mg-1 protein
      and 4.29+/-2.10 nmol GSH mg-1 protein, respectively). They were compared with
      levels of specific inductors of these biochemical markers in muscle. The results
      confirmed contamination of some river locations (Labe Obristvi, Svratka).

PMID- 27879838
TI  - Energy-efficient Organization of Wireless Sensor Networks with Adaptive
      Forecasting.
AB  - Due to the wide potential applications of wireless sensor networks, this topic
      has attracted great attention. The strict energy constraints of sensor nodes
      result in great challenges for energy efficiency. This paper proposes an energy
      efficient organization method. The organization of wireless sensor networks is
      formulated for target tracking. Target localization is achieved by collaborative
      sensing with multi-sensor fusion. The historical localization results are
      utilized for adaptive target trajectory forecasting. Combining autoregressive
      moving average (ARMA) model and radial basis function networks (RBFNs), robust
      target position forecasting is performed. Moreover, an energyefficient
      organization method is presented to enhance the energy efficiency of wireless
      sensor networks. The sensor nodes implement sensing tasks are awakened in a
      distributed manner. When the sensor nodes transfer their observations to achieve
      data fusion, the routing scheme is obtained by ant colony optimization. Thus,
      both the operation and communication energy consumption can be minimized.
      Experimental results verify that the combination of ARMA model and RBFN can
      estimate the target position efficiently and energy saving is achieved by the
      proposed organization method in wireless sensor networks.

PMID- 27879839
TI  - Temporal Variability Corrections for Advanced Microwave Scanning Radiometer E
      (AMSR-E) Surface Soil Moisture: Case Study in Little River Region, Georgia, U.S.
AB  - Statistical correction methods, the Cumulative Distribution Function (CDF)
      matching technique and Regional Statistics Method (RSM) are applied to adjust the
      limited temporal variability of Advanced Microwave Scanning Radiometer E (AMSR-E)
      data using the Common Land Model (CLM). The temporal variability adjustment
      between CLM and AMSR-E data was conducted for annual and seasonal periods for
      2003 in the Little River region, GA. The results showed that the statistical
      correction techniques improved AMSR-E's limited temporal variability as compared
      to ground-based measurements. The regression slope and intercept improved from
      0.210 and 0.112 up to 0.971 and -0.005 for the non-growing season. The R2 values
      also modestly improved. The Moderate Resolution Imaging Spectroradiometer (MODIS)
      Leaf Area Index (LAI) products were able to identify periods having an attenuated
      microwave brightness signal that are not likely to benefit from these statistical
      correction techniques.

PMID- 27879841
TI  - High Sensitivity MEMS Strain Sensor: Design and Simulation.
AB  - In this article, we report on the new design of a miniaturized strain
      microsensor. The proposed sensor utilizes the piezoresistive properties of doped
      single crystal silicon. Employing the Micro Electro Mechanical Systems (MEMS)
      technology, high sensor sensitivities and resolutions have been achieved. The
      current sensor design employs different levels of signal amplifications. These
      amplifications include geometric, material and electronic levels. The sensor and
      the electronic circuits can be integrated on a single chip, and packaged as a
      small functional unit. The sensor converts input strain to resistance change,
      which can be transformed to bridge imbalance voltage. An analog output that
      demonstrates high sensitivity (0.03mV/me), high absolute resolution (1MUe) and
      low power consumption (100MUA) with a maximum range of +/-4000MUe has been
      reported. These performance characteristics have been achieved with high signal
      stability over a wide temperature range (+/-50oC), which introduces the proposed
      MEMS strain sensor as a strong candidate for wireless strain sensing applications
      under harsh environmental conditions. Moreover, this sensor has been designed,
      verified and can be easily modified to measure other values such as force,
      torque...etc. In this work, the sensor design is achieved using Finite Element
      Method (FEM) with the application of the piezoresistivity theory. This design
      process and the microfabrication process flow to prototype the design have been
      presented.

PMID- 27879840
TI  - Pathogen Phytosensing: Plants to Report Plant Pathogens.
AB  - Real-time systems that provide evidence of pathogen contamination in crops can be
      an important new line of early defense in agricultural centers. Plants possess
      defense mechanisms to protect against pathogen attack. Inducible plant defense is
      controlled by signal transduction pathways, inducible promoters and cis
      regulatory elements corresponding to key genes involved in defense, and pathogen
      specific responses. Identified inducible promoters and cis-acting elements could
      be utilized in plant sentinels, or 'phytosensors', by fusing these to reporter
      genes to produce plants with altered phenotypes in response to the presence of
      pathogens. Here, we have employed cis-acting elements from promoter regions of
      pathogen inducible genes as well as those responsive to the plant defense signal
      molecules salicylic acid, jasmonic acid, and ethylene. Synthetic promoters were
      constructed by combining various regulatory elements supplemented with the
      enhancer elements from the Cauliflower mosaic virus (CaMV) 35S promoter to
      increase basal level of the GUS expression. The inducibility of each synthetic
      promoter was first assessed in transient expression assays using Arabidopsis
      thaliana protoplasts and then examined for efficacy in stably transgenic
      Arabidopsis and tobacco plants. Histochemical and fluorometric GUS expression
      analyses showed that both transgenic Arabidopsis and tobacco plants responded to
      elicitor and phytohormone treatments with increased GUS expression when compared
      to untreated plants. Pathogen-inducible phytosensor studies were initiated by
      analyzing the sensitivity of the synthetic promoters against virus infection.
      Transgenic tobacco plants infected with Alfalfa mosaic virus showed an increase
      in GUS expression when compared to mock-inoculated control plants, whereas
      Tobacco mosaic virus infection caused no changes in GUS expression. Further
      research, using these transgenic plants against a range of different pathogens
      with the regulation of detectable reporter gene could provide biological evidence
      to define the functional differences between pathogens, and provide new
      technology and applications for transgenic plants as phytosensors.

PMID- 27879842
TI  - CMOS Humidity Sensor System Using Carbon Nitride Film as Sensing Materials.
AB  - An integrated humidity sensor system with nano-structured carbon nitride film as
      humidity sensing material is fabricated by a 0.8 MUm analog mixed CMOS process.
      The integrated sensor system consists of differential humidity sensitive field
      effect transistors (HUSFET), temperature sensor, and operational amplifier. The
      process contains two poly, two metal and twin well technology. To form CNx film
      on Si3N4/Si substrate, plasma etching is performed to the gate area as well as
      trenches. CNx film is deposited by reactive RF magnetron sputtering method and
      patterned by the lift-off technique. The drain current is proportional to the
      dielectric constant, and the sensitivity is 2.8 ?/%RH.

PMID- 27879843
TI  - Multidirectional Scanning Model, MUSCLE, to Vectorize Raster Images with Straight
      Lines.
AB  - This paper presents a new model, MUSCLE (Multidirectional Scanning for Line
      Extraction), for automatic vectorization of raster images with straight lines.
      The algorithm of the model implements the line thinning and the simple
      neighborhood methods to perform vectorization. The model allows users to define
      specified criteria which are crucial for acquiring the vectorization process. In
      this model, various raster images can be vectorized such as township plans, maps,
      architectural drawings, and machine plans. The algorithm of the model was
      developed by implementing an appropriate computer programming and tested on a
      basic application. Results, verified by using two well known vectorization
      programs (WinTopo and Scan2CAD), indicated that the model can successfully
      vectorize the specified raster data quickly and accurately.

PMID- 27879844
TI  - Downscaling Thermal Infrared Radiance for Subpixel Land Surface Temperature
      Retrieval.
AB  - Land surface temperature (LST) retrieved from satellite thermal sensors often
      consists of mixed temperature components. Retrieving subpixel LST is therefore
      needed in various environmental and ecological studies. In this paper, we
      developed two methods for downscaling coarse resolution thermal infrared (TIR)
      radiance for the purpose of subpixel temperature retrieval. The first method was
      developed on the basis of a scale-invariant physical model on TIR radiance. The
      second method was based on a statistical relationship between TIR radiance and
      land cover fraction at high spatial resolution. The two methods were applied to
      downscale simulated 990-m ASTER TIR data to 90-m resolution. When validated
      against the original 90-m ASTER TIR data, the results revealed that both
      downscaling methods were successful in capturing the general patterns of the
      original data and resolving considerable spatial details. Further quantitative
      assessments indicated a strong agreement between the true values and the
      estimated values by both methods.

PMID- 27879845
TI  - Working Principle Simulations of a Dynamic ResonantWall Shear Stress Sensor
      Concept.
AB  - This paper discusses a novel dynamic resonant wall shear stress sensor concept
      based on an oscillating sensor operating near resonance. The interaction between
      the oscillating sensor surface and the fluid above it is modelled using the
      unsteady laminar boundary layer equations. The numerical experiment shows that
      the effect of the oscillating shear stress is well correlated by the Hummer
      number, the ratio of the steady shear force caused by the outside flow to the
      oscillating viscous force created by the sensor motion. The oscillating shear
      stress predicted by the fluid model is used in a mechanical model of the sensor
      to predict the sensor's dynamic motion. Static calibration curves for amplitude
      and frequency influences are predicted. These results agree with experimental
      results on some extent, and shows some expectation for further development of the
      dynamic resonant sensor concept.

PMID- 27879847
TI  - Intercomparison of Evapotranspiration Over the Savannah Volta Basin in West
      Africa Using Remote Sensing Data.
AB  - This paper compares evapotranspiration estimates from two complementary satellite
      sensors - NASA's Moderate Resolution Imaging Spectroradiometer (MODIS) and ESA's
      ENVISAT Advanced Along-Track Scanning Radiometer (AATSR) over the savannah area
      of the Volta basin in West Africa. This was achieved through solving for
      evapotranspiration on the basis of the regional energy balance equation, which
      was computationally-driven by the Surface Energy Balance Algorithm for Land
      algorithm (SEBAL). The results showed that both sensors are potentially good
      sources of evapotranspiration estimates over large heterogeneous landscapes. The
      MODIS sensor measured daily evapotranspiration reasonably well with a strong
      spatial correlation (R2=0.71) with Landsat ETM+ but underperformed with
      deviations up to ~2.0 mm day-1, when compared with local eddy correlation
      observations and the Penman-Monteith method mainly because of scale mismatch. The
      AATSR sensor produced much poorer correlations (R2=0.13) with Landsat ETM+ and
      conventional ET methods also because of differences in atmospheric correction and
      sensor calibration over land.

PMID- 27879846
TI  - Visible Genotype Sensor Array.
AB  - A visible sensor array system for simultaneous multiple SNP genotyping has been
      developed using a new plastic base with specific surface chemistry.
      Discrimination of SNP alleles is carried out by an allele-specific extension
      reaction using immobilized oligonucleotide primers. The 3'-ends of
      oligonucleotide primers are modified with a locked nucleic acid to enhance their
      efficiency in allelic discrimination. Biotin-dUTPs included in the reaction
      mixture are selectively incorporated into extending primer sequences and are
      utilized as tags for alkaline phosphatase-mediated precipitation of colored
      chemical substrates onto the surface of the plastic base. The visible
      precipitates allow immediate inspection of typing results by the naked eye and
      easy recording by a digital camera equipped on a commercial mobile phone. Up to
      four individuals can be analyzed on a single sensor array and multiple sensor
      arrays can be handled in a single operation. All of the reactions can be
      performed within one hour using conventional laboratory instruments. This visible
      genotype sensor array is suitable for "focused genomics" that follows
      "comprehensive genomics".

PMID- 27879848
TI  - Deployment of a Prototype Plant GFP Imager at the Arthur Clarke Mars Greenhouse
      of the Haughton Mars Project.
AB  - The use of engineered plants as biosensors has made elegant strides in the past
      decades, providing keen insights into the health of plants in general and
      particularly in the nature and cellular location of stress responses. However,
      most of the analytical procedures involve laboratory examination of the biosensor
      plants. With the advent of the green fluorescence protein (GFP) as a biosensor
      molecule, it became at least theoretically possible for analyses of gene
      expression to occur telemetrically, with the gene expression information of the
      plant delivered to the investigator over large distances simply as properly
      processed fluorescence images. Spaceflight and other extraterrestrial
      environments provide unique challenges to plant life, challenges that often
      require changes at the gene expression level to accommodate adaptation and
      survival. Having previously deployed transgenic plant biosensors to evaluate
      responses to orbital spaceflight, we wished to develop the plants and especially
      the imaging devices required to conduct such experiments robotically, without
      operator intervention, within extraterrestrial environments. This requires the
      development of an autonomous and remotely operated plant GFP imaging system and
      concomitant development of the communications infrastructure to manage dataflow
      from the imaging device. Here we report the results of deploying a prototype GFP
      imaging system within the Arthur Clarke Mars Greenhouse (ACMG) an autonomously
      operated greenhouse located within the Haughton Mars Project in the Canadian High
      Arctic. Results both demonstrate the applicability of the fundamental GFP
      biosensor technology and highlight the difficulties in collecting and managing
      telemetric data from challenging deployment environments.

PMID- 27879849
TI  - Relative Radiometric Normalization and Atmospheric Correction of a SPOT 5 Time
      Series.
AB  - Multi-temporal images acquired at high spatial and temporal resolution are an
      important tool for detecting change and analyzing trends, especially in
      agricultural applications. However, to insure a reliable use of this kind of
      data, a rigorous radiometric normalization step is required. Normalization can be
      addressed by performing an atmospheric correction of each image in the time
      series. The main problem is the difficulty of obtaining an atmospheric
      characterization at a given acquisition date. In this paper, we investigate
      whether relative radiometric normalization can substitute for atmospheric
      correction. We develop an automatic method for relative radiometric normalization
      based on calculating linear regressions between unnormalized and reference
      images. Regressions are obtained using the reflectances of automatically selected
      invariant targets. We compare this method with an atmospheric correction method
      that uses the 6S model. The performances of both methods are compared using 18
      images from of a SPOT 5 time series acquired over Reunion Island. Results
      obtained for a set of manually selected invariant targets show excellent
      agreement between the two methods in all spectral bands: values of the
      coefficient of determination (r2) exceed 0.960, and bias magnitude values are
      less than 2.65. There is also a strong correlation between normalized NDVI values
      of sugarcane fields (r2 = 0.959). Despite a relative error of 12.66% between
      values, very comparable NDVI patterns are observed.

PMID- 27879850
TI  - Relocating Sensor Nodes to Maximize Cumulative Connected Coverage in Wireless
      Sensor Networks.
AB  - In order to extend the availability of the wireless sensor network and to extract
      maximum possible information from the surveillance area, proper usage of the
      power capacity of the sensor nodes is important. Our work describes a dynamic
      relocation algorithm called MaxNetLife, which is mainly based on utilizing the
      remaining power of individual sensor nodes as well as properly relocating sensor
      nodes so that all sensor nodes can transmit the data they sense to the sink.
      Hence, the algorithm maximizes total collected information from the surveillance
      area before the possible death of the sensor network by increasing cumulative
      connected coverage parameter of the network. A deterministic approach is used to
      deploy sensor nodes into the sensor field where Hexagonal Grid positioning is
      used to address and locate each sensor node. Sensor nodes those are not planned
      to be actively used in the close future in a specific cell are preemptively
      relocated to the cells those will be in need of additional sensor nodes to
      improve cumulative connected coverage of the network. MaxNetLife algorithm also
      includes the details of the relocation activities, which include preemptive
      migration of the redundant nodes to the cells before any coverage hole occurs
      because of death of a sensor node. Relocation Model, Data Aggregation Model, and
      Energy model of the algorithm are studied in detail. MaxNetLife algorithm is
      proved to be effective, scalable, and applicable through simulations.

PMID- 27879852
TI  - Alpine Grassland Phenology as Seen in AVHRR, VEGETATION, and MODIS NDVI Time
      Series - a Comparison with In Situ Measurements.
AB  - This study evaluates the ability to track grassland growth phenology in the Swiss
      Alps with NOAA-16 Advanced Very High Resolution Radiometer (AVHRR) Normalized
      Difference Vegetation Index (NDVI) time series. Three growth parameters from 15
      alpine and subalpine grassland sites were investigated between 2001 and 2005:
      Melt-Out (MO), Start Of Growth (SOG), and End Of Growth (EOG).We tried to
      estimate these phenological dates from yearly NDVI time series by identifying
      dates, where certain fractions (thresholds) of the maximum annual NDVI amplitude
      were crossed for the first time. For this purpose, the NDVI time series were
      smoothed using two commonly used approaches (Fourier adjustment or alternatively
      Savitzky-Golay filtering). Moreover, AVHRR NDVI time series were compared against
      data from the newer generation sensors SPOT VEGETATION and TERRA MODIS. All
      remote sensing NDVI time series were highly correlated with single point ground
      measurements and therefore accurately represented growth dynamics of alpine
      grassland. The newer generation sensors VGT and MODIS performed better than
      AVHRR, however, differences were minor. Thresholds for the determination of MO,
      SOG, and EOG were similar across sensors and smoothing methods, which
      demonstrated the robustness of the results. For our purpose, the Fourier
      adjustment algorithm created better NDVI time series than the Savitzky-Golay
      filter, since latter appeared to be more sensitive to noisy NDVI time series.
      Findings show that the application of various thresholds to NDVI time series
      allows the observation of the temporal progression of vegetation growth at the
      selected sites with high consistency. Hence, we believe that our study helps to
      better understand largescale vegetation growth dynamics above the tree line in
      the European Alps.

PMID- 27879851
TI  - Assessment of Organophosphate and Carbamate Pesticide Residues in Cigarette
      Tobacco with a Novel Cell Biosensor.
AB  - The conventional analysis of pesticide residues in analytical commodities, such
      as tobacco and tobacco products is a labor intensive procedure, since it is
      necessary to cover a wide range of different chemicals, using a single procedure.
      Standard analysis methods include extensive sample pretreatment (with solvent
      extraction and partitioning phases) and determination by GC and HPLC to achieve
      the necessary selectivity and sensitivity for the different classes of compounds
      under detection. As a consequence, current methods of analysis provide a limited
      sample capacity. In the present study, we report on the development of a novel
      cell biosensor for detecting organophosphate and carbamate pesticide residues in
      tobacco. The sensor is based on neuroblastoma N2a cells and the measurement of
      changes of the cell membrane potential, according to the working principle of the
      Bioelectric Recognition Assay (BERA). The presence of pesticide residues is
      detected by the degree of inhibition of acetylcholine esterase (AChE). The sensor
      instantly responded to both the organophoshate pesticide chlorpyriphos and the
      carbamate carbaryl in a concentration-dependent pattern, being able to detect one
      part per billion (1 ppb). Additionally, tobacco leaf samples (in blended dry
      form) were analyzed with both the novel biosensor and conventional methods,
      according to a double-blind protocol. Pesticide residues in tobacco samples
      caused a considerable cell membrane hyperpolarization to neuroblastoma cells
      immobilized in the sensor, as indicated by the increase of the negative sensor
      potential, which was clearly distinguishable from the sensor's response against
      pesticide-free control samples. The observed response was quite reproducible,
      with an average variation of +5,6%. Fluorescence microscopy observations showed
      that treatment of the cells with either chlorpyrifos or carbaryl was associated
      with increased [Ca2+]cyt . The novel biosensor offers fresh perspectives for
      ultra-rapid, sensitive and low-cost monitoring of pesticide residues in tobacco
      as well as other food and agricultural commodities.

PMID- 27879854
TI  - Feature Extraction and Spatial Interpolation for Improved Wireless Location
      Sensing.
AB  - This paper proposes a new methodology to improve location-sensing accuracy in
      wireless network environments eliminating the effects of non-line-of-sight
      errors. After collecting bulks of anonymous location measurements from a wireless
      network, the preparation stage of the proposed methodology begins. Investigating
      the collected location measurements in terms of signal features and geometric
      features, feature locations are identified. After the identification of feature
      locations, the non-line-of-sight error correction maps are generated. During the
      real-time location sensing stage, each user can request localization with a set
      of location measurements. With respected to the reported measurements, the pre
      computed correction maps are applied. As a result, localization accuracy improves
      by eliminating the non-line-of-sight errors. A simulation result, assuming a
      typical dense urban environment, demonstrates the benefits of the proposed
      location sensing methodology.

PMID- 27879853
TI  - Molecularly Imprinted Polymers: Thermodynamic and Kinetic Considerations on the
      Specific Sorption and Molecular Recognition.
AB  - This article presents a work aiming at thermodynamically and kinetically
      interpreting the specific sorption and recognition by a molecularly imprinted
      polymer. Using Boc-L-Phe-OH as a template, the imprinted material was prepared.
      The result indicates that the prepared polymer can well discriminate the imprint
      species from its analogue (Boc-D-Phe-OH), so as to adsorb more for the former but
      less for the latter. Kinetic analysis indicates that this specific sorption, in
      nature, can be a result of a preferential promotion. The imprint within the
      polymer causes a larger adsorption rate for the template than for the analogue.
      Thermodynamic study also implies that the molecular induction from the specific
      imprint to the template is larger than to the analogue, which thus makes the
      polymer capable of preferentially alluring the template to bind.

PMID- 27879855
TI  - An Integrated MEMS Gyroscope Array with Higher Accuracy Output.
AB  - In this paper, an integrated MEMS gyroscope array method composed of two levels
      of optimal filtering was designed to improve the accuracy of gyroscopes. In the
      firstlevel filtering, several identical gyroscopes were combined through Kalman
      filtering into a single effective device, whose performance could surpass that of
      any individual sensor. The key of the performance improving lies in the optimal
      estimation of the random noise sources such as rate random walk and angular
      random walk for compensating the measurement values. Especially, the cross
      correlation between the noises from different gyroscopes of the same type was
      used to establish the system noise covariance matrix and the measurement noise
      covariance matrix for Kalman filtering to improve the performance further.
      Secondly, an integrated Kalman filter with six states was designed to further
      improve the accuracy with the aid of external sensors such as magnetometers and
      accelerometers in attitude determination. Experiments showed that three
      gyroscopes with a bias drift of 35 degree per hour could be combined into a
      virtual gyroscope with a drift of 1.07 degree per hour through the first-level
      filter, and the bias drift was reduced to 0.53 degree per hour after the second
      level filtering. It proved that the proposed integrated MEMS gyroscope array is
      capable of improving the accuracy of the MEMS gyroscopes, which provides the
      possibility of using these low cost MEMS sensors in high-accuracy application
      areas.

PMID- 27879856
TI  - Hemispheric Lateralization of Event-Related Brain Potentials in Different
      Processing Phases during Unimanual Finger Movements.
AB  - Previous functional MRI and brain electrophysiology studies have studied the left
      right differences during the tapping tasks and found that the activation of left
      hemisphere was more significant than that of right hemisphere. In this study, we
      wanted to delineate this lateralization phenomenon not only in the execution
      phase but also in other processing phases, such as early visual, pre-executive
      and post-executive phases. We have designed a finger-tapping task to delineate
      the left-right differences of event related potentials (ERPs) to right finger
      movement in sixteen right handed college students. The mean amplitudes of ERPs
      were analyzed to examine the left-right dominance of cortical activity in the
      phase of early visual process (75-120ms), pre-execution (175-260ms), execution
      (310-420ms) and post-execution (420-620ms). In the execution phase, ERPs at the
      left electrodes were significantly more pronounced than those at the right
      electrodes (F3 > F4, C3 > C4, P3 > P4, O1 > O2) under the situation without
      comparing the central electrodes (Fz, Cz, Pz, and Oz). No difference was found
      between left and right electrodes in other three phases except the C3 electrode
      still showed more dominant than C4 in the pre- and post-execution phase. In
      conclusion, the phenomenon of brain lateralization occur major in the execution
      phase. The central area also showed the lateralization in the pre- and post
      execution to demonstrate its unique lateralized contributions to unilateral
      simple finger movements.

PMID- 27879857
TI  - Modeling Spatio-Temporal Dynamics of Optimum Tilt Angles for Solar Collectors in
      Turkey.
AB  - Quantifying spatial and temporal variations in optimal tilt angle of a solar
      collector relative to a horizontal position assists in maximizing its performance
      for energy collection depending on changes in time and space. In this study,
      optimal tilt angles were quantified for solar collectors based on the monthly
      global and diffuse solar radiation on a horizontal surface across Turkey. The
      dataset of monthly average daily global solar radiation was obtained from 158
      places, and monthly diffuse radiation data were estimated using an empirical
      model in the related literature. Our results showed that high tilt angles during
      the autumn (September to November) and winter (December to February) and low tilt
      angles during the summer (March to August) enabled the solar collector surface to
      absorb the maximum amount of solar radiation. Monthly optimum tilt angles were
      estimated devising a sinusoidal function of latitude and day of the year, and
      their validation resulted in a high R2 value of 98.8%, with root mean square
      error (RMSE) of 2.06o.

PMID- 27879859
TI  - Using SPOT-5 HRG Data in Panchromatic Mode for Operational Detection of Small
      Ships in Tropical Area.
AB  - Nowadays, there is a growing interest in applications of space remote sensing
      systems for maritime surveillance which includes among others traffic
      surveillance, maritime security, illegal fisheries survey, oil discharge and sea
      pollution monitoring. Within the framework of several French and European
      projects, an algorithm for automatic ship detection from SPOT-5 HRG data was
      developed to complement existing fishery control measures, in particular the
      Vessel Monitoring System. The algorithm focused on feature-based analysis of
      satellite imagery. Genetic algorithms and Neural Networks were used to deal with
      the feature-borne information. Based on the described approach, a first prototype
      was designed to classify small targets such as shrimp boats and tested on
      panchromatic SPOT-5, 5-m resolution product taking into account the environmental
      and fishing context. The ability to detect shrimp boats with satisfactory
      detection rates is an indicator of the robustness of the algorithm. Still, the
      benchmark revealed problems related to increased false alarm rates on particular
      types of images with a high percentage of cloud cover and a sea cluttered
      background.

PMID- 27879858
TI  - Nanorobot Hardware Architecture for Medical Defense.
AB  - This work presents a new approach with details on the integrated platform and
      hardware architecture for nanorobots application in epidemic control, which
      should enable real time in vivo prognosis of biohazard infection. The recent
      developments in the field of nanoelectronics, with transducers progressively
      shrinking down to smaller sizes through nanotechnology and carbon nanotubes, are
      expected to result in innovative biomedical instrumentation possibilities, with
      new therapies and efficient diagnosis methodologies. The use of integrated
      systems, smart biosensors, and programmable nanodevices are advancing
      nanoelectronics, enabling the progressive research and development of molecular
      machines. It should provide high precision pervasive biomedical monitoring with
      real time data transmission. The use of nanobioelectronics as embedded systems is
      the natural pathway towards manufacturing methodology to achieve nanorobot
      applications out of laboratories sooner as possible. To demonstrate the practical
      application of medical nanorobotics, a 3D simulation based on clinical data
      addresses how to integrate communication with nanorobots using RFID, mobile
      phones, and satellites, applied to long distance ubiquitous surveillance and
      health monitoring for troops in conflict zones. Therefore, the current model can
      also be used to prevent and save a population against the case of some targeted
      epidemic disease.

PMID- 27879860
TI  - Analysis of Electromyographic Signals from Rats' Stomaches for Detection and
      Classification of Motility.
AB  - This paper presents the analysis of the electromyographic signals from rat
      stomaches to identify and classify contractions. The results were validated with
      both visual identification and an ultrasonic system to guarantee the reference.
      Some parameters were defined and associated to the energy of the signal in
      frequency domain and grouped in a P vector. The parameters were statistically
      analyzed and according to the results, an artificial neuronal network was
      designed to use the P vectors as inputs to classify the electrical signals
      related to the contraction conditions. A first approach classification was
      performed with and without contraction classes (CR and NCR), then the same
      database were subdivided in four classes: with induced contraction (ICR),
      spontaneous contraction (SCR), without contraction due a post mortem condition
      (PMR) or under physiological conditions (PNCR). In a two-class classifier,
      performance was 86%, 93% and 91% of detections for each electrogastromyografic
      (EGMG) signal from each of three pairs of electrodes considered. Because in the
      four-class classifier, enough data was not collected for the first pair, then a
      three-class classifier with 82% of performance was used. For the other two EGMG
      signals electrode pairs, performance was of 76% and 86% respectively. Based in
      the results, the analysis of P vectors could be used as a contraction detector in
      motility studies due to different stimuli in a rat model.

PMID- 27879861
TI  - Hydrologic Remote Sensing and Land Surface Data Assimilation.
AB  - Accurate, reliable and skillful forecasting of key environmental variables such
      as soil moisture and snow are of paramount importance due to their strong
      influence on many water resources applications including flood control,
      agricultural production and effective water resources management which
      collectively control the behavior of the climate system. Soil moisture is a key
      state variable in land surface-atmosphere interactions affecting surface energy
      fluxes, runoff and the radiation balance. Snow processes also have a large
      influence on land-atmosphere energy exchanges due to snow high albedo, low
      thermal conductivity and considerable spatial and temporal variability resulting
      in the dramatic change on surface and ground temperature. Measurement of these
      two variables is possible through variety of methods using ground-based and
      remote sensing procedures. Remote sensing, however, holds great promise for soil
      moisture and snow measurements which have considerable spatial and temporal
      variability. Merging these measurements with hydrologic model outputs in a
      systematic and effective way results in an improvement of land surface model
      prediction. Data Assimilation provides a mechanism to combine these two sources
      of estimation. Much success has been attained in recent years in using data from
      passive microwave sensors and assimilating them into the models. This paper
      provides an overview of the remote sensing measurement techniques for soil
      moisture and snow data and describes the advances in data assimilation techniques
      through the ensemble filtering, mainly Ensemble Kalman filter (EnKF) and Particle
      filter (PF), for improving the model prediction and reducing the uncertainties
      involved in prediction process. It is believed that PF provides a complete
      representation of the probability distribution of state variables of interests
      (according to sequential Bayes law) and could be a strong alternative to EnKF
      which is subject to some limitations including the linear updating rule and
      assumption of jointly normal distribution of errors in state variables and
      observation.

PMID- 27879862
TI  - PAU/GNSS-R: Implementation, Performance and First Results of a Real-Time Delay
      Doppler Map Reflectometer Using Global Navigation Satellite System Signals.
AB  - Signals from Global Navigation Satellite Systems (GNSS) were originally conceived
      for position and speed determination, but they can be used as signals of
      opportunity as well. The reflection process over a given surface modifies the
      properties of the scattered signal, and therefore, by processing the reflected
      signal, relevant geophysical data regarding the surface under study (land, sea,
      ice...) can be retrieved. In essence, a GNSS-R receiver is a multi-channel GNSS
      receiver that computes the received power from a given satellite at a number of
      different delay and Doppler bins of the incoming signal. The first approaches to
      build such a receiver consisted of sampling and storing the scattered signal for
      later post-processing. However, a real-time approach to the problem is desirable
      to obtain immediately useful geophysical variables and reduce the amount of data.
      The use of FPGA technology makes this possible, while at the same time the system
      can be easily reconfigured. The signal tracking and processing constraints made
      necessary to fully design several new blocks. The uniqueness of the implemented
      system described in this work is the capability to compute in real-time Delay
      Doppler maps (DDMs) either for four simultaneous satellites or just one, but with
      a larger number of bins. The first tests have been conducted from a cliff over
      the sea and demonstrate the successful performance of the instrument to compute
      DDMs in real-time from the measured reflected GNSS/R signals. The processing of
      these measurements shall yield quantitative relationships between the sea state
      (mainly driven by the surface wind and the swell) and the overall DDM shape. The
      ultimate goal is to use the DDM shape to correct the sea state influence on the L
      band brightness temperature to improve the retrieval of the sea surface salinity
      (SSS).

PMID- 27879863
TI  - Seasonal Effect on Tree Species Classification in an Urban Environment Using
      Hyperspectral Data, LiDAR, and an Object- Oriented Approach.
AB  - The objective of the current study was to analyze the seasonal effect on
      differentiating tree species in an urban environment using multi-temporal
      hyperspectral data, Light Detection And Ranging (LiDAR) data, and a tree species
      database collected from the field. Two Airborne Imaging Spectrometer for
      Applications (AISA) hyperspectral images were collected, covering the Summer and
      Fall seasons. In order to make both datasets spatially and spectrally compatible,
      several preprocessing steps, including band reduction and a spatial degradation,
      were performed. An object-oriented classification was performed on both images
      using training data collected randomly from the tree species database. The seven
      dominant tree species (Gleditsia triacanthos, Acer saccharum, Tilia Americana,
      Quercus palustris, Pinus strobus and Picea glauca) were used in the
      classification. The results from this analysis did not show any major difference
      in overall accuracy between the two seasons. Overall accuracy was approximately
      57% for the Summer dataset and 56% for the Fall dataset. However, the Fall
      dataset provided more consistent results for all tree species while the Summer
      dataset had a few higher individual class accuracies. Further, adding LiDAR into
      the classification improved the results by 19% for both fall and summer. This is
      mainly due to the removal of shadow effect and the addition of elevation data to
      separate low and high vegetation.

PMID- 27879864
TI  - On Line Disaster Response Community: People as Sensors of High Magnitude
      Disasters Using Internet GIS.
AB  - The Indian Ocean tsunami (2004) and Hurricane Katrina (2005) reveal the coming of
      age of the on-line disaster response community. Due to the integration of key
      geospatial technologies (remote sensing - RS, geographic information systems -
      GIS, global positioning systems - GPS) and the Internet, on-line disaster
      response communities have grown. They include the traditional aspects of disaster
      preparedness, response, recovery, mitigation, and policy as facilitated by
      governmental agencies and relief response organizations. However, the
      contribution from the public via the Internet has changed significantly. The on
      line disaster response community includes several key characteristics: the
      ability to donate money quickly and efficiently due to improved Internet security
      and reliable donation sites; a computer-savvy segment of the public that creates
      blogs, uploads pictures, and disseminates information - oftentimes faster than
      government agencies, and message boards to create interactive information
      exchange in seeking family members and identifying shelters. A critical and novel
      occurrence is the development of "people as sensors" - networks of government,
      NGOs, private companies, and the public - to build rapid response databases of
      the disaster area for various aspects of disaster relief and response using
      geospatial technologies. This paper examines these networks, their products, and
      their future potential.

PMID- 27879865
TI  - A Novel Modified Omega-K Algorithm for Synthetic Aperture Imaging Lidar through
      the Atmosphere.
AB  - The spatial resolution of a conventional imaging lidar system is constrained by
      the diffraction limit of the telescope's aperture. The combination of the lidar
      and synthetic aperture (SA) processing techniques may overcome the diffraction
      limit and pave the way for a higher resolution air borne or space borne remote
      sensor. Regarding the lidar transmitting frequency modulation continuous-wave
      (FMCW) signal, the motion during the transmission of a sweep and the reception of
      the corresponding echo were expected to be one of the major problems. The given
      modified Omega-K algorithm takes the continuous motion into account, which can
      compensate for the Doppler shift induced by the continuous motion efficiently and
      azimuth ambiguity for the low pulse recurrence frequency limited by the tunable
      laser. And then, simulation of Phase Screen (PS) distorted by atmospheric
      turbulence following the von Karman spectrum by using Fourier Transform is
      implemented in order to simulate turbulence. Finally, the computer simulation
      shows the validity of the modified algorithm and if in the turbulence the
      synthetic aperture length does not exceed the similar coherence length of the
      atmosphere for SAIL, we can ignore the effect of the turbulence.

PMID- 27879866
TI  - Wireless Network for Measurement of Whole-Body Vibration.
AB  - This article presents the development of a system integrated to a ZigBee network
      to measure whole-body vibration. The developed system allows distinguishing human
      vibrations of almost 400Hz in three axes with acceleration of almost 50g. The
      tests conducted in the study ensured the correct functioning of the system for
      the project's purpose.

PMID- 27879867
TI  - Near-Infrared Fluorescent Materials for Sensing of Biological Targets.
AB  - Near-infrared fluorescent (NIRF) materials are promising labeling reagents for
      sensitive determination and imaging of biological targets. In the near-infrared
      region biological samples have low background fluorescence signals, providing
      high signal to noise ratio. Meanwhile, near-infrared radiation can penetrate into
      sample matrices deeply due to low light scattering. Thus, in vivo and in vitro
      imaging of biological samples can be achieved by employing the NIRF probes. To
      take full advantage of NIRF materials in the biological and biomedical field, one
      of the key issues is to develop intense and biocompatible NIRF probes. In this
      review, a number of NIRF materials are discussed including traditional NIRF dye
      molecules, newly developed NIRF quantum dots and single-walled carbon nanotubes,
      as well as rare earth metal compounds. The use of some NIRF materials in various
      nanostructures is illustrated. The enhancement of NIRF using metal nanostructures
      is covered as well. The fluorescence mechanism and bioapplications of each type
      of the NIRF materials are discussed in details.

PMID- 27879869
TI  - Plant Species Recovery on a Compacted Skid Road.
AB  - This study was executed to determine the plant species of herbaceous cover in a
      skid road subjected to soil compaction due to timber skidding in a beech (Fagus
      orientalis Lipsky.) stand. Our previous studies have shown that ground based
      timber skidding destroys the soils extremely, and degradations on ecosystem
      because of the timber skidding limit recovery and growth of plant cover on skid
      roads. However, some plant species show healthy habitat, recovery and they can
      survive after the extreme degradation in study area. We evaluated composition of
      these plant species and their cover-abundance scales in 100 m x 3 m transect. 15
      plant species were determined belongs to 12 plant families and Liliaceae was the
      highest representative plant family. Smilax aspera L., Epimedium pubigerum (DC.)
      Moren et Decaisne, Carex distachya Desf. var. distachya Desf., Pteridium
      aquilinum (L.) Kuhn., Trachystemon orientalis (L.) G. Don, Hedera helix L. have
      the highest coverabundance scale overall of determined species on compacted skid
      road.

PMID- 27879870
TI  - The Landcover Impact on the Aspect/Slope Accuracy Dependence of the SRTM-1
      Elevation Data for the Humboldt Range.
AB  - The U.S. National Landcover Dataset (NLCD) and the U.S National Elevation Dataset
      (NED) (bare earth elevations) were used in an attempt to assess to what extent
      the directional and slope dependency of the Shuttle Radar Topography Mission
      (SRTM) finished digital elevation model is affected by landcover. Four landcover
      classes: forest, shrubs, grass and snow cover, were included in the study area
      (Humboldt Range in NW portion of Nevada, USA). Statistics, rose diagrams, and
      frequency distributions of the elevation differences (NED-SRTM) per landcover
      class per geographic direction were used. The decomposition of elevation
      differences on the basis of aspect and slope terrain classes identifies a) over
      estimation of elevation by the SRTM instrument along E, NE and N directions
      (negative elevation difference that decreases linearly with slope) while b)
      underestimation is evident towards W, SW and S directions (positive elevation
      difference increasing with slope). The aspect/slope/landcover elevation
      differences modelling overcome the systematic errors evident in the SRTM dataset
      and revealed vegetation height information and the snow penetration capability of
      the SRTM instrument. The linear regression lines per landcover class might
      provide means of correcting the systematic error (aspect/slope dependency)
      evident in SRTM dataset.

PMID- 27879871
TI  - A Low-Cost CMOS Programmable Temperature Switch.
AB  - A novel uncalibrated CMOS programmable temperature switch with high temperature
      accuracy is presented. Its threshold temperature Tth can be programmed by
      adjusting the ratios of width and length of the transistors. The operating
      principles of the temperature switch circuit is theoretically explained. A
      floating gate neural MOS circuit is designed to compensate automatically the
      threshold temperature Tth variation that results form the process tolerance. The
      switch circuit is implemented in a standard 0.35 MUm CMOS process. The
      temperature switch can be programmed to perform the switch operation at 16
      different threshold temperature Tths from 45-120 degrees C with a 5 degrees C
      increment. The measurement shows a good consistency in the threshold
      temperatures. The chip core area is 0.04 mm2 and power consumption is 3.1 MUA at
      3.3V power supply. The advantages of the temperature switch are low power
      consumption, the programmable threshold temperature and the controllable
      hysteresis.

PMID- 27879868
TI  - Utilizing of Adsorptive Transfer Stripping Technique Brdicka Reaction for
      Determination of Metallothioneins Level in Melanoma Cells, Blood Serum and
      Tissues.
AB  - In the paper we utilized the adsorptive transfer stripping differential pulse
      voltammetry Brdicka reaction for the determination of metallothioneins (MT) in
      melanoma cells, animal melanoma tissues (MeLiM miniature pig) and blood serum of
      patients with malignant melanoma. Primarily we attempted to investigate the
      influence of dilution of real sample on MT electrochemical response. Dilution of
      samples of 1 000 times was chosen the most suitable for determination of MT level
      in biological samples. Then we quantified the MT level in the melanoma cells, the
      animal melanoma tissues and the blood serum samples. The MT content in the cells
      varied within the range from 4.2 to 11.2 MUM. At animal melanoma tissues
      (melanomas localized on abdomen, back limb and dorsum) the highest content of MT
      was determined in the tumour sampled on the back of the animal and was nearly 500
      MUg of MTs per gram of a tissue. We also quantified content of MT in metastases,
      which was found in liver, spleen and lymph nodes. Moreover the average MT level
      in the blood serum samples from patients with melanoma was 3.0 +/- 0.8 MUM. MT
      levels determined at melanoma samples were significantly (p < 0.05) higher
      compared to control ones at cells, tissues and blood serum.

PMID- 27879872
TI  - Electrochemical Determination of Low Molecular Mass Thiols Content in Potatoes
      (Solanum tuberosum) Cultivated in the Presence of Various Sulphur Forms and
      Infected by Late Blight (Phytophora infestans).
AB  - In the present paper potato plants were cultivated in the presence of ammonium
      sulphate or elemental sulphur supplementation into the soil to reveal the effects
      of different sulphur forms on content of nitrogen, phosphorus, potassium,
      calcium, magnesium and sulphur, and yield of tubers. During the investigation of
      the influence of different sulphur forms on yield of potato tubers we did not
      observe significant changes. Average weight of tubers of control plants per one
      experimental pot was 355 g. Application of sulphur in both forms resulted in
      moderate potato tubers weight reduction per one experimental pot compared to
      control group; average value ranged from 320 to 350 g per one experimental pot.
      Further we treated the plants with two different supplementation of sulphur with
      cadmium(II) ions (4 mg of cadmium(II) acetate per kilogram of the soil). The
      significantly lowest cadmium content (p < 0.05) was determined in tissues of
      plants treated with the highest dosage of elemental sulphur (0.64 mg Cd/kg)
      compared to control plants (0.82 mg Cd/kg). We also aimed our attention on the
      cadmium content in proteins, lipids or soluble carbohydrates and ash. Application
      of sulphate as well as elemental sulphur resulted in significant cadmium content
      reduction in lipid fraction compared to control plants. In addition to this we
      quantified content of low molecular mass thiols in potatoes tissues. To determine
      the thiols content we employed differential pulse voltammetry Brdicka reaction.
      After twelve days of the treatment enhancing of thiols level was observed in all
      experimental groups regardless to applied sulphur form and its concentration.
      Finally we evaluated the effect of sulphur supplementation on Phytophora
      infestans infection of potato plants.

PMID- 27879873
TI  - Implantable Microimagers.
AB  - Implantable devices such as cardiac pacemakers, drug-delivery systems, and
      defibrillators have had a tremendous impact on the quality of live for many
      disabled people. To date, many devices have been developed for implantation into
      various parts of the human body. In this paper, we focus on devices implanted in
      the head. In particular, we describe the technologies necessary to create
      implantable microimagers. Design, fabrication, and implementation issues are
      discussed vis-a-vis two examples of implantable microimagers; the retinal
      prosthesis and in vivo neuro-microimager. Testing of these devices in animals
      verify the use of the microimagers in the implanted state. We believe that
      further advancement of these devices will lead to the development of a new method
      for medical and scientific applications.

PMID- 27879875
TI  - ASPIS, A Flexible Multispectral System for Airborne Remote Sensing Environmental
      Applications.
AB  - Airborne multispectral and hyperspectral remote sensing is a powerful tool for
      environmental monitoring applications. In this paper we describe a new system
      (ASPIS) composed by a 4-CCD spectral sensor, a thermal IR camera and a laser
      altimeter that is mounted on a flexible Sky-Arrow airplane. A test application of
      the multispectral sensor to estimate durum wheat quality is also presented.

PMID- 27879874
TI  - Signature Optical Cues: Emerging Technologies for Monitoring Plant Health.
AB  - Optical technologies can be developed as practical tools for monitoring plant
      health by providing unique spectral signatures that can be related to specific
      plant stresses. Signatures from thermal and fluorescence imaging have been used
      successfully to track pathogen invasion before visual symptoms are observed.
      Another approach for noninvasive plant health monitoring involves elucidating the
      manner with which light interacts with the plant leaf and being able to identify
      changes in spectral characteristics in response to specific stresses. To achieve
      this, an important step is to understand the biochemical and anatomical features
      governing leaf reflectance, transmission and absorption. Many studies have opened
      up possibilities that subtle changes in leaf reflectance spectra can be analyzed
      in a plethora of ways for discriminating nutrient and water stress, but with
      limited success. There has also been interest in developing transgenic
      phytosensors to elucidate plant status in relation to environmental conditions.
      This approach involves unambiguous signal creation whereby genetic modification
      to generate reporter plants has resulted in distinct optical signals emitted in
      response to specific stressors. Most of these studies are limited to laboratory
      or controlled greenhouse environments at leaf level. The practical translation of
      spectral cues for application under field conditions at canopy and regional
      levels by remote aerial sensing remains a challenge. The movement towards
      technology development is well exemplified by the Controlled Ecological Life
      Support System under development by NASA which brings together technologies for
      monitoring plant status concomitantly with instrumentation for environmental
      monitoring and feedback control.

PMID- 27879876
TI  - Opto-Electric Cellular Biosensor Using Optically Transparent Indium Tin Oxide
      (ITO) Electrodes.
AB  - Indium tin oxide (ITO) biosensors are used to perform simultaneous optical and
      electrical measurements in order to examine the dynamic cellular attachment,
      spreading, and proliferation of endothelial cells (ECs) as well as cytotoxic
      effects when exposed to cytochalasin D. A detailed description of the fabrication
      of these sensors is provided and their superior optical characteristics are
      qualitatively shown using four different microscopic images. Differential
      interference contrast microscopy (DICM) images were acquired simultaneously with
      micro-impedance measurements as a function of frequency and time. A digital image
      processing algorithm quantified the cell-covered electrode area as a function of
      time. In addition, cytotoxicity effects, produced by the toxic agent cytochalasin
      D, were examined using micro-impedance measurements, confocal microscopy images
      of stained actin-filaments, and interference reflection contrast microscopy
      (IRCM) capable of examining the bottom morphology of a cell. The results of this
      study show (1) the dynamic optical and electrical cellular characteristics using
      optically thin ITO biosensors; (2) qualitative agreement between cell-covered
      electrode area and electrical impedance during cellular attachment; (3) in vitro
      cytotoxicity detection of ECs due to 3 mM cytochalasin D. The present opto
      electric biosensor system is unique in that a simultaneous and integrated
      cellular analysis is possible for a variety of living cells.

PMID- 27879877
TI  - Environmental Harmony and Evaluation of Advertisement Billboards with Digital
      Photogrammetry Technique and GIS Capabilities: A Case Study in the City of
      Ankara.
AB  - Geographical Information Systems (GIS) have been gaining a growing interest in
      Turkey. Many local governments and public agencies have been struggling to set up
      such systems to serve the needs and meet public requirements. Urban life shelters
      the advertisement reality which is presented at various places, on vehicles,
      shops etc. in daily life. It can be said that advertisement is a part of daily
      life in urban area, especially in city centers. In addition, one of the main
      sources of revenue for municipalities comes from advertising and notices. The
      advertising sector provides a great level of income today. Therefore advertising
      is individually very important for local governments and urban management.
      Although it is valuable for local governments, it is also very important for
      urban management to place these advertisement signs and billboards in an orderly
      fashion which is pleasing to the eye. Another point related to this subject is
      the systematic control mechanism which is necessary for collecting taxes
      regularly and updating. In this paper, first practical meaning of notice and
      advertisement subject, problem definition and objectives are described and then
      legal support and daily practice are revised. Current practice and problems are
      mentioned. Possibilities of measuring and obtaining necessary information by
      using digital images and transferring them to spatial databases are studied. By
      this study, a modern approach was developed for urban management and
      municipalities by using information technology which is an alternative to current
      application. Criteria which provide environmental harmony such as urban beauty,
      colour, compatibility and safety were also evaluated. It was finally concluded
      that measuring commercial signs and keeping environmental harmony under control
      for urban beauty can be provided by Digital Photogrammetry (DP) technique and GIS
      capabilities which were studied with pilot applications in the city center of
      Ankara.

PMID- 27879878
TI  - Methods for Improving Image Quality and Reducing Data Load of NIR Hyperspectral
      Images.
AB  - Near Infrared Hyperspectral Imaging (NIRHSI) is an emerging technology platform
      that integrates conventional imaging and spectroscopy to attain both spatial and
      spectral information from an object. Two important problems in NIRHSI are those
      of data load and unserviceable pixels in the NIR sensor. Hyperspectral imaging
      experiments generate large amounts of data (typically > 50 MB per image), which
      tend to overwhelm the memory capacity of conventional computer systems. This
      inhibits the utilisation of NIRHSI for routine online industrial application. In
      general, approximately 1% of pixels in NIR detectors are unserviceable or 'dead',
      containing no useful information. While this percentage of pixels is
      insignificant for single wavelength imaging, the problem is amplified in NIRHSI,
      where > 100 wavelength images are typically acquired. This paper describes an
      approach for reducing the data load of hyperspectral experiments by using sample
      specific vector-to-scalar operators for real time feature extraction and a
      systematic procedure for compensating for 'dead' pixels in the NIR sensor. The
      feasibility of this approach was tested for prediction of moisture content in
      carrot tissue.

PMID- 27879879
TI  - Hyperspectral Sensor Data Capability for Retrieving Complex Urban Land Cover in
      Comparison with Multispectral Data: Venice City Case Study (Italy).
AB  - This study aims at comparing the capability of different sensors to detect land
      cover materials within an historical urban center. The main objective is to
      evaluate the added value of hyperspectral sensors in mapping a complex urban
      context. In this study we used: (a) the ALI and Hyperion satellite data, (b) the
      LANDSAT ETM+ satellite data, (c) MIVIS airborne data and (d) the high spatial
      resolution IKONOS imagery as reference. The Venice city center shows a complex
      urban land cover and therefore was chosen for testing the spectral and spatial
      characteristics of different sensors in mapping the urban tissue. For this
      purpose, an object-oriented approach and different common classification methods
      were used. Moreover, spectra of the main anthropogenic surfaces (i.e. roofing and
      paving materials) were collected during the field campaigns conducted on the
      study area. They were exploited for applying band-depth and sub-pixel analyses to
      subsets of Hyperion and MIVIS hyperspectral imagery. The results show that
      satellite data with a 30m spatial resolution (ALI, LANDSAT ETM+ and HYPERION) are
      able to identify only the main urban land cover materials.

PMID- 27879880
TI  - A SAR Observation and Numerical Study on Ocean Surface Imprints of Atmospheric
      Vortex Streets.
AB  - The sea surface imprints of Atmospheric Vortex Street (AVS) off Aleutian Volcanic
      Islands, Alaska were observed in two RADARSAT-1 Synthetic Aperture Radar (SAR)
      images separated by about 11 hours. In both images, three pairs of distinctive
      vortices shedding in the lee side of two volcanic mountains can be clearly seen.
      The length and width of the vortex street are about 60-70 km and 20 km,
      respectively. Although the AVS's in the two SAR images have similar shapes, the
      structure of vortices within the AVS is highly asymmetrical. The sea surface wind
      speed is estimated from the SAR images with wind direction input from Navy NOGAPS
      model. In this paper we present a complete MM5 model simulation of the observed
      AVS. The surface wind simulated from the MM5 model is in good agreement with SAR
      derived wind. The vortex shedding rate calculated from the model run is about 1
      hour and 50 minutes. Other basic characteristics of the AVS including propagation
      speed of the vortex, Strouhal and Reynolds numbers favorable for AVS generation
      are also derived. The wind associated with AVS modifies the cloud structure in
      the marine atmospheric boundary layer. The AVS cloud pattern is also observed on
      a MODIS visible band image taken between the two RADARSAT SAR images. An ENVISAT
      advance SAR image taken 4 hours after the second RADARSAT SAR image shows that
      the AVS has almost vanished.

PMID- 27879882
TI  - Detection of Simulated Defect Using IR Temperature Sensors and One Point Heating.
AB  - Infrared temperature sensors, simple device for temperature measurement, have
      been modified for the measurement of temperature distribution on the metal
      surface in a way of nondestructive detection of defects of the object. In this
      study, the IR sensor system is utilized for the defect detection in a cylinder
      with one point heating, and the performance of the system is examined with an
      aluminum cylinder having a simulated defect. In addition, a 3-D conduction
      equation is numerically solved to compare the computed temperature profile with
      the measured one. The experimental outcome indicates that the defect detection is
      readily available with the proposed device and the point heating is practical for
      the applications of the defect detection. It is also found that the measured
      temperature distribution is comparable to the computed result from the conduction
      equation.

PMID- 27879881
TI  - Non-Invasive Glucose Measurement by Use of Metabolic Heat Conformation Method.
AB  - A non-invasive glucose measurement system based on the method of metabolic heat
      conformation (MHC) is presented in this paper. This system consists of three
      temperature sensors, two humidity sensors, an infrared sensor and an optical
      measurement device. The glucose level can be deduced from the quantity of heat
      dissipation, blood flow rate of local tissue and degree of blood oxygen
      saturation. The methodology of the data process and the measurement error are
      also analyzed. The system is applied in a primary clinical test. Compared with
      the results of a commercial automated chemistry analyzer, the correlation
      coefficient of the collected data from the system is 0.856. Result shows that the
      correlation coefficient improves when the factor of heat dissipated by
      evaporation of the skin is added in. A non-invasive method of measuring the blood
      flow rate of local tissue by heat transmission between skin and contacted
      conductor is also introduced. Theoretical derivation and numerical simulation are
      completed as well. The so-called normalized difference mean (NDM) is chosen to
      express the quantity of the blood flow rate. The correlation coefficient between
      the blood flow rates by this method and the results of a Doppler blood flow meter
      is equal to 0.914.

PMID- 27879883
TI  - Optical Remote Sensing of Glacier Characteristics: A Review with Focus on the
      Himalaya.
AB  - The increased availability of remote sensing platforms with appropriate spatial
      and temporal resolution, global coverage and low financial costs allows for fast,
      semi-automated, and cost-effective estimates of changes in glacier parameters
      over large areas. Remote sensing approaches allow for regular monitoring of the
      properties of alpine glaciers such as ice extent, terminus position, volume and
      surface elevation, from which glacier mass balance can be inferred. Such methods
      are particularly useful in remote areas with limited field-based glaciological
      measurements. This paper reviews advances in the use of visible and infrared
      remote sensing combined with field methods for estimating glacier parameters,
      with emphasis on volume/area changes and glacier mass balance. The focus is on
      the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor
      and its applicability for monitoring Himalayan glaciers. The methods reviewed
      are: volumetric changes inferred from digital elevation models (DEMs), glacier
      delineation algorithms from multi-spectral analysis, changes in glacier area at
      decadal time scales, and AAR/ELA methods used to calculate yearly mass balances.
      The current limitations and on-going challenges in using remote sensing for
      mapping characteristics of mountain glaciers also discussed, specifically in the
      context of the Himalaya.

PMID- 27879884
TI  - SAR System for UAV Operation with Motion Error Compensation beyond the Resolution
      Cell.
AB  - This paper presents an experimental Synthetic Aperture Radar (SAR) system that is
      under development in the Universidad Politecnica de Madrid. The system uses
      Linear Frequency Modulated Continuous Wave (LFM-CW) radar with a two antenna
      configuration for transmission and reception. The radar operates in the
      millimeter-wave band with a maximum transmitted bandwidth of 2 GHz. The proposed
      system is being developed for Unmanned Aerial Vehicle (UAV) operation. Motion
      errors in UAV operation can be critical. Therefore, this paper proposes a method
      for focusing SAR images with movement errors larger than the resolution cell.
      Typically, this problem is solved using two processing steps: first, coarse
      motion compensation based on the information provided by an Inertial Measuring
      Unit (IMU); and second, fine motion compensation for the residual errors within
      the resolution cell based on the received raw data. The proposed technique tries
      to focus the image without using data of an IMU. The method is based on a
      combination of the well known Phase Gradient Autofocus (PGA) for SAR imagery and
      typical algorithms for translational motion compensation on Inverse SAR (ISAR).
      This paper shows the first real experiments for obtaining high resolution SAR
      images using a car as a mobile platform for our radar.

PMID- 27879885
TI  - Hardware Implementation of Multiple Fan Beam Projection Technique in Optical
      Fibre Process Tomography.
AB  - The main objective of this project is to implement the multiple fan beam
      projection technique using optical fibre sensors with the aim to achieve a high
      data acquisition rate. Multiple fan beam projection technique here is defined as
      allowing more than one emitter to transmit light at the same time using the
      switch-mode fan beam method. For the thirty-two pairs of sensors used, the 2
      projection technique and 4- projection technique are being investigated. Sixteen
      sets of projections will complete one frame of light emission for the 2
      projection technique while eight sets of projection will complete one frame of
      light emission for the 4-projection technique. In order to facilitate data
      acquisition process, PIC microcontroller and the sample and hold circuit are
      being used. This paper summarizes the hardware configuration and design for this
      project.

PMID- 27879886
TI  - Motion Compensation of Moving Targets for High Range Resolution Stepped-Frequency
      Radar.
AB  - High range resolution (HRR) profiling using stepped-frequency pulse trains
      suffers from range shift and the attenuation/dispersion of range profiles while
      the target of interest is moving. To overcome these two drawbacks, a new
      algorithm based on the maximum likelihood (ML) estimation is proposed in this
      paper. Without altering the conventional stepped-frequency waveform, this
      algorithm can estimate the target velocity and thereby compensate the phase
      errors caused by the target's motion. It is shown that the velocity can be
      accurately estimated and the range profile can be correctly reconstructed.

PMID- 27879887
TI  - A Two Dimensional Overlapped Subaperture Polar Format Algorithm Based on Stepped
      chirp Signal.
AB  - In this work, a 2-D subaperture polar format algorithm (PFA) based on
      steppedchirp signal is proposed. Instead of traditional pulse synthesis
      preprocessing, the presented method integrates the pulse synthesis process into
      the range subaperture processing. Meanwhile, due to the multi-resolution property
      of subaperture processing, this algorithm is able to compensate the space-variant
      phase error caused by the radar motion during the period of a pulse cluster.
      Point target simulation has validated the presented algorithm.

PMID- 27879888
TI  - Sensing and 3D Mapping of Soil Compaction.
AB  - Soil compaction is an important physical limiting factor for the root growth and
      plant emergence and is one of the major causes for reduced crop yield worldwide.
      The objective of this study was to generate 2D/3D soil compaction maps for
      different depth layers of the soil. To do so, a soil penetrometer was designed,
      which was mounted on the three-point hitch of an agricultural tractor, consisting
      of a mechanical system, data acquisition system (DAS), and 2D/3D imaging and
      analysis software. The system was successfully tested in field conditions,
      measuring soil penetration resistances as a function of depth from 0 to 40 cm at
      1 cm intervals. The software allows user to either tabulate the measured
      quantities or generate maps as soon as data collection has been terminated. The
      system may also incorporate GPS data to create geo-referenced soil maps. The
      software enables the user to graph penetration resistances at a specified
      coordinate. Alternately, soil compaction maps could be generated using data
      collected from multiple coordinates. The data could be automatically stratified
      to determine soil compaction distribution at different layers of 5, 10,...., 40
      cm depths. It was concluded that the system tested in this study could be used to
      assess the soil compaction at topsoil and the randomly distributed hardpan
      formations just below the common tillage depths, enabling visualization of
      spatial variability through the imaging software.

PMID- 27879889
TI  - Assessing the Potentialities of FORMOSAT-2 Data for Water and Crop Monitoring at
      Small Regional Scale in South-Eastern France.
AB  - Water monitoring at the scale of a small agricultural region is a key point to
      insure a good crop development particularly in South-Eastern France, where
      extreme climatic conditions result in long dry periods in spring and summer with
      very sparse precipitation events, corresponding to a crucial period of crop
      development. Remote sensing with the increasing imagery resolution is a useful
      tool to provide information on plant water status over various temporal and
      spatial scales. The current study focussed on assessing the potentialities of
      FORMOSAT-2 data, characterized by high spatial (8m pixel) and temporal
      resolutions (1-3 day/time revisit), to improve crop modeling and spatial
      estimation of the main land properties. Thirty cloud free images were acquired
      from March to October 2006 over a small region called Crau-Camargue in SE France,
      while numerous ground measurements were performed simultaneously over various
      crop types. We have compared two models simulating energy transfers between soil,
      vegetation and atmosphere: SEBAL and PBLs. Maps of evapotranspiration were
      analyzed according to the agricultural practices at field scale. These practices
      were well identified from FORMOSAT-2 images, which provided accurate input
      surface parameters to the SVAT models.

PMID- 27879890
TI  - Reflectance Modeling for Real Snow Structures Using a Beam Tracing Model.
AB  - It is important to understand reflective properties of snow, for example for
      remote sensing applications and for modeling of energy balances in snow packs. We
      present a method with which we can compare reflectance measurements and
      calculations for the same snow sample structures. Therefore, we first tomograph
      snow samples to acquire snow structure images (6 x 2 mm). Second, we calculated
      the sample reflectance by modeling the radiative transfer, using a beam tracing
      model. This model calculates the biconical reflectance (BR) derived from an
      arbitrary number of incident beams. The incident beams represent a diffuse light
      source. We applied our method to four different snow samples: Fresh snow,
      metamorphosed snow, depth hoar, and wet snow. The results show that (i) the
      calculated and measured reflectances agree well and (ii) the model produces
      different biconical reflectances for different snow types. The ratio of the
      structure to the wavelength is large. We estimated that the size parameter is
      larger than 50 in all cases we analyzed. Specific surface area of the snow
      samples explains most of the difference in radiance, but not the different
      biconical reflectance distributions. The presented method overcomes the
      limitations of common radiative transfer models which use idealized grain shapes
      such as spheres, plates, needles and hexagonal particles. With this method we
      could improve our understanding for changes in biconical reflectance distribution
      associated with changes in specific surface area.

PMID- 27879891
TI  - Measurement of Mechanical Properties of Cantilever Shaped Materials.
AB  - Microcantilevers were first introduced as imaging probes in Atomic Force
      Microscopy (AFM) due to their extremely high sensitivity in measuring surface
      forces. The versatility of these probes, however, allows the sensing and
      measurement of a host of mechanical properties of various materials. Sensor
      parameters such as resonance frequency, quality factor, amplitude of vibration
      and bending due to a differential stress can all be simultaneously determined for
      a cantilever. When measuring the mechanical properties of materials, identifying
      and discerning the most influential parameters responsible for the observed
      changes in the cantilever response are important. We will, therefore, discuss the
      effects of various force fields such as those induced by mass loading, residual
      stress, internal friction of the material, and other changes in the mechanical
      properties of the microcantilevers. Methods to measure variations in temperature,
      pressure, or molecular adsorption of water molecules are also discussed. Often
      these effects occur simultaneously, increasing the number of parameters that need
      to be concurrently measured to ensure the reliability of the sensors. We
      therefore systematically investigate the geometric and environmental effects on
      cantilever measurements including the chemical nature of the underlying
      interactions. To address the geometric effects we have considered cantilevers
      with a rectangular or circular cross section. The chemical nature is addressed by
      using cantilevers fabricated with metals and/or dielectrics. Selective chemical
      etching, swelling or changes in Young's modulus of the surface were investigated
      by means of polymeric and inorganic coatings. Finally to address the effect of
      the environment in which the cantilever operates, the Knudsen number was
      determined to characterize the molecule-cantilever collisions. Also bimaterial
      cantilevers with high thermal sensitivity were used to discern the effect of
      temperature variations. When appropriate, we use continuum mechanics, which is
      justified according to the ratio between the cantilever thickness and the grain
      size of the materials. We will also address other potential applications such as
      the ageing process of nuclear materials, building materials, and optical fibers,
      which can be investigated by monitoring their mechanical changes with time. In
      summary, by virtue of the dynamic response of a miniaturized cantilever shaped
      material, we present useful measurements of the associated elastic properties.

PMID- 27879892
TI  - Remote Sensing and Wetland Ecology: a South African Case Study.
AB  - Remote sensing offers a cost efficient means for identifying and monitoring
      wetlands over a large area and at different moments in time. In this study, we
      aim at providing ecologically relevant information on characteristics of
      temporary and permanent isolated open water wetlands, obtained by standard
      techniques and relatively cheap imagery. The number, surface area, nearest
      distance, and dynamics of isolated temporary and permanent wetlands were
      determined for the Western Cape, South Africa. Open water bodies (wetlands) were
      mapped from seven Landsat images (acquired during 1987 - 2002) using supervised
      maximum likelihood classification. The number of wetlands fluctuated over time.
      Most wetlands were detected in the winter of 2000 and 2002, probably related to
      road constructions. Imagery acquired in summer contained fewer wetlands than in
      winter. Most wetlands identified from Landsat images were smaller than one
      hectare. The average distance to the nearest wetland was larger in summer. In
      comparison to temporary wetlands, fewer, but larger permanent wetlands were
      detected. In addition, classification of non-vegetated wetlands on an Envisat
      ASAR radar image (acquired in June 2005) was evaluated. The number of detected
      small wetlands was lower for radar imagery than optical imagery (acquired in June
      2002), probably because of deterioration of the spatial information content due
      the extensive pre-processing requirements of the radar image. Both optical and
      radar classifications allow to assess wetland characteristics that potentially
      influence plant and animal metacommunity structure. Envisat imagery, however, was
      less suitable than Landsat imagery for the extraction of detailed ecological
      information, as only large wetlands can be detected. This study has indicated
      that ecologically relevant data can be generated for the larger wetlands through
      relatively cheap imagery and standard techniques, despite the relatively low
      resolution of Landsat and Envisat imagery. For the characterisation of very small
      wetlands, high spatial resolution optical or radar images are needed. This study
      exemplifies the benefits of integrating remote sensing and ecology and hence
      stimulates interdisciplinary research of isolated wetlands.

PMID- 27879893
TI  - Assessment of Unmanned Aerial Vehicles Imagery for Quantitative Monitoring of
      Wheat Crop in Small Plots.
AB  - This paper outlines how light Unmanned Aerial Vehicles (UAV) can be used in
      remote sensing for precision farming. It focuses on the combination of simple
      digital photographic cameras with spectral filters, designed to provide
      multispectral images in the visible and near-infrared domains. In 2005, these
      instruments were fitted to powered glider and parachute, and flown at six dates
      staggered over the crop season. We monitored ten varieties of wheat, grown in
      trial micro-plots in the South-West of France. For each date, we acquired
      multiple views in four spectral bands corresponding to blue, green, red, and near
      infrared. We then performed accurate corrections of image vignetting, geometric
      distortions, and radiometric bidirectional effects. Afterwards, we derived for
      each experimental micro-plot several vegetation indexes relevant for vegetation
      analyses. Finally, we sought relationships between these indexes and field
      measured biophysical parameters, both generic and date-specific. Therefore, we
      established a robust and stable generic relationship between, in one hand, leaf
      area index and NDVI and, in the other hand, nitrogen uptake and GNDVI. Due to a
      high amount of noise in the data, it was not possible to obtain a more accurate
      model for each date independently. A validation protocol showed that we could
      expect a precision level of 15% in the biophysical parameters estimation while
      using these relationships.

PMID- 27879894
TI  - Estimation of Actual Evapotranspiration by Remote Sensing: Application in
      Thessaly Plain, Greece.
AB  - Remote sensing can assist in improving the estimation of the geographical
      distribution of evapotranspiration, and consequently water demand in large
      cultivated areas for irrigation purposes and sustainable water resources
      management. In the direction of these objectives, the daily actual
      evapotranspiration was calculated in this study during the summer season of 2001
      over the Thessaly plain in Greece, a wide irrigated area of great agricultural
      importance. Three different methods were adapted and applied: the remotesensing
      methods by Granger (2000) and Carlson and Buffum (1989) that use satellite data
      in conjunction with ground meteorological measurements and an adapted FAO (Food
      and Agriculture Organisation) Penman-Monteith method (Allen at al. 1998), which
      was selected to be the reference method. The satellite data were used in
      conjunction with ground data collected on the three closest meteorological
      stations. All three methods, exploit visible channels 1 and 2 and infrared
      channels 4 and 5 of NOAA-AVHRR (National Oceanic and Atmospheric Administration -
      Advanced Very High Resolution Radiometer) sensor images to calculate albedo and
      NDVI (Normalised Difference Vegetation Index), as well as surface temperatures.
      The FAO Penman-Monteith and the Granger method have used exclusively NOAA-15
      satellite images to obtain mean surface temperatures. For the Carlson-Buffum
      method a combination of NOAA-14 and NuOmicronAlphaAlpha-15 satellite images was
      used, since the average rate of surface temperature rise during the morning was
      required. The resulting estimations show that both the Carlson-Buffum and Granger
      methods follow in general the variations of the reference FAO Penman-Monteith
      method. Both methods have potential for estimating the spatial distribution of
      evapotranspiration, whereby the degree of the relative agreement with the
      reference FAO Penman-Monteith method depends on the crop growth stage. In
      particular, the Carlson- Buffum method performed better during the first half of
      the crop development stage, while the Granger method performed better during the
      remaining of the development stage and the entire maturing stage. The parameter
      that influences the estimations significantly is the wind speed whose high values
      result in high underestimates of evapotranspiration. Thus, it should be studied
      further in future.

PMID- 27879895
TI  - Air Pollution Monitoring and Mining Based on Sensor Grid in London.
AB  - In this paper, we present a distributed infrastructure based on wireless sensors
      network and Grid computing technology for air pollution monitoring and mining,
      which aims to develop low-cost and ubiquitous sensor networks to collect real
      time, large scale and comprehensive environmental data from road traffic
      emissions for air pollution monitoring in urban environment. The main informatics
      challenges in respect to constructing the high-throughput sensor Grid are
      discussed in this paper. We present a twolayer network framework, a P2P e-Science
      Grid architecture, and the distributed data mining algorithm as the solutions to
      address the challenges. We simulated the system in TinyOS to examine the
      operation of each sensor as well as the networking performance. We also present
      the distributed data mining result to examine the effectiveness of the algorithm.

PMID- 27879896
TI  - DNA Extraction Systematics for Spectroscopic Studies.
AB  - Study of genetic material allows the comprehension the origin of the many
      biochemical changes that follow diseases, like cancer, promoting the development
      of early preventive inquiry and more efficient individual treatments. Raman
      spectroscopy can be an important tool in DNA study, since it allows probe
      molecular vibrations of genetic material in a fast way. The present work
      established a systematic way for extract DNA in suitable concentrations and
      structural integrity allowing studies by Raman spectroscopy or other
      spectroscopic technique, including bio-analytical sensors for probing genetic
      alterations.

PMID- 27879897
TI  - Free and Forced Rossby Waves in the Western South China Sea Inferred from Jason-1
      Satellite Altimetry Data.
AB  - Data from a subsurface mooring deployed in the western South China Sea shows
      clear intra-seasonal oscillations (ISO) at the period of 40~70 days. Analysis of
      remotelysensed sea surface height (SSH) anomalies in the same area indicates that
      these ISO signals propagate both eastward and westward. Time-longitude diagrams
      of ISO signals in SSH anomalies and wind-stress curl indicate that the eastward
      propagating SSH anomalies is forced by wind-stress curl. This is also confirmed
      by lag correlation between SSH anomalies and the wind-stress-curl index (wind
      stress curl averaged over 109.5oE -115oE and 12oN -13.5oN). Lag correlation of
      SSH anomaly suggests that the westward propagating signals are free Rossby waves.

PMID- 27879899
TI  - An Investigation on Micro-Raman Spectra and Wavelet Data Analysis for Pemphigus
      Vulgaris Follow-up Monitoring.
AB  - A wavelet multi-component decomposition algorithm has been used for data analysis
      of micro-Raman spectra of blood serum samples from patients affected by pemphigus
      vulgaris at different stages. Pemphigus is a chronic, autoimmune, blistering
      disease of the skin and mucous membranes with a potentially fatal outcome.
      Spectra were measured by means of a Raman confocal microspectrometer apparatus
      using the 632.8 nm line of a He-Ne laser source. A discrete wavelet transform
      decomposition method has been applied to the recorded Raman spectra in order to
      overcome problems related to low-level signals and the presence of noise and
      background components due to light scattering and fluorescence. This numerical
      data treatment can automatically extract quantitative information from the Raman
      spectra and makes more reliable the data comparison. Even if an exhaustive
      investigation has not been done in this work, the feasibility of the follow-up
      monitoring of pemphigus vulgaris pathology has been clearly proved with useful
      implications for the clinical applications.

PMID- 27879900
TI  - Disposable E-Tongue for the Assessment of Water Quality in Fish Tanks.
AB  - A disposable screen-printed e-tongue based on sensor array and pattern
      recognition that is suitable for the assessment of water quality in fish tanks is
      described. The characteristics of sensors fabricated using two kinds of sensing
      materials, namely (i) lipids (referred to as Type 1), and (ii) alternative
      electroactive materials comprising liquid ion-exchangers and macrocyclic
      compounds (Type 2) were evaluated for their performance stability, sensitivity
      and reproducibility. The Type 2 e-tongue was found to have better sensing
      performance in terms of sensitivity and reproducibility and was thus used for
      application studies. By using a pattern recognition tool i.e. principal component
      analysis (PCA), the e-tongue was able to discriminate the changes in the water
      quality in tilapia and catfish tanks monitored over eight days. E-tongues coupled
      with partial least squares (PLS) was used for the quantitative analysis of
      nitrate and ammonium ions in catfish tank water and good agreement were found
      with the ion-chromatography method (relative error, +/-1.04- 4.10 %).

PMID- 27879898
TI  - Using Electromyography to Detect the Weightings of the Local Muscle Factors to
      the Increase of Perceived Exertion During Stepping Exercise.
AB  - Rate of perceived exertion (RPE) is a clinically convenient indicator for
      monitoring exercise intensity in cardiopulmonary rehabilitation. It might not be
      sensitive enough for clinicians to determine the patients' physiological status
      because its association with the cardiovascular system and local muscle factors
      is unknown. This study used the electromyographic sensor to detect the local
      muscle fatigue and stabilization of patella, and analyzed the relationship
      between various local muscle and cardiovascular factors and the increase of RPE
      during stepping exercise, a common exercise program provided in cardiopulmonary
      rehabilitation. Ten healthy adults (4 males and 6 females) participated in this
      study. Each subject used their right bare foot to step up onto a 23-cm-high step
      at a constant speed until the RPE score reached 20. The RPE, heart rate (HR), and
      surface EMG of the rectus femoris (RF), vastus medialis, and vastus lateralis
      were recorded at 1-minute intervals during the stepping exercise. The generalized
      estimating equations (GEE) analysis indicated that the increase in RPE
      significantly correlated with the increase in HR, and decrease in median
      frequency (MF) of the EMG power spectrum of the RF. Experimental results suggest
      that the increase in RPE during stepping exercise was influenced by the
      cardiovascular status, localized muscle fatigue in the lower extremities. The
      weighting of the local muscle factors was more than half of the weighting of the
      cardiovascular factor.

PMID- 27879901
TI  - Flow-Injection Coulometric Detection Based on Ion Transfer and Its Application to
      the Determination of Chlorpromazine.
AB  - A flow-injection coulometric method for the determination of chlorpromazine based
      on ion transfer into a plasticized poly(vinyl chloride) (PVC) membrane, was
      developed. The detector used consists of a flow-through cell that incorporates a
      plasticized poly(vinyl chloride) (PVC) membrane which contains tetrabutylammonium
      tetraphenylborate as electrolyte. The membrane is located between the flowing
      solution and an inner aqueous electrolyte solution. Two pairs of electrodes, each
      pair formed by a reference electrode and a working electrode, are used, one pair
      in each solution. The potential between the reference electrodes was controlled
      by a four-electrode potentiostat with ohmic drop compensation. A potential step
      capable of producing the transfer of the chlorpromazine ion into the membrane was
      applied during the passage of a wide portion of sample plug through the cell and
      the corresponding quantity of the electricity was measured. In the selected
      conditions, a linear relationship was observed between the quantity of
      electricity and chlorpromazine concentrations over a range of 1x10-6 -1x10-4 M.
      The detection limit was 2 x 10-7 M. Good repeatability and between-day
      reproducibility was obtained. No interference was observed on the part of some
      common ions and pharmaceutical excipients. The method proposed was applied
      satisfactorily to the determination of chlorpromazine in pharmaceuticals and
      human urine.

PMID- 27879902
TI  - Fluorescent Indolizine-b-Cyclodextrin Derivatives for the Detection of Volatile
      Organic Compounds.
AB  - This paper presents the synthesis, the structural determination and the sensing
      capabilities toward Volatile Organic Compounds (VOCs) of a new class of
      fluorescent indolizine-cyclodextrin sensors. Two different pathways, both
      involving bipyridinium ylides and 6-amino-b-cyclodextrin, have been used to carry
      out the synthesis of these sensors. The macrocycle structures were dominantly
      established by 1H-NMR spectra and systematically studied by molecular modelling
      (MM3, AM1, AM1-COSMO methods). The sensing capabilities of the sensors were
      evaluated by emission of fluorescence, during the inclusion of the guest
      (adamantanol or aromatic derivatives) into the cyclodextrin (CD) host cavity. The
      host/guest complex formation was investigated by formation constant
      determinations, using experimental methods, coupled with theoretical calculations
      of formation energies using a specific docking procedure. Both experimental and
      theoretical results suggest that some compounds would make very attractive
      sensors for VOC detection. Some compounds could also be taken into consideration
      as biological markers.

PMID- 27879903
TI  - Dynamic Characteristics of Vertically Coupled Structures and the Design of a
      Decoupled Micro Gyroscope.
AB  - In a vertical type, vibratory gyroscope, the coupled motion between reference
      (driving) and sensing vibrations causes the zero-point output, which is the
      unwanted sensing vibration without angular velocity. This structural coupling
      leads to an inherent discrepancy between the natural frequencies of the reference
      and the sensing oscillations, causing curve veering in frequency loci. The
      coupled motion deteriorates sensing performance and dynamic stability. In this
      paper, the dynamic characteristics associated with the coupling phenomenon are
      theoretically analyzed. The effects of reference frequency and coupling factor on
      the rotational direction and amplitude of elliptic oscillation are determined.
      Based on the analytical studies on the coupling effects, we propose and fabricate
      a vertically decoupled vibratory gyroscope with the frequency matching.

PMID- 27879904
TI  - Sensor for Measuring Strain in Textile.
AB  - In this paper a stain sensor to measure large strain (80%) in textiles is
      presented. It consists of a mixture of 50wt-% thermoplastic elastomer (TPE) and
      50wt-% carbon black particles and is fiber-shaped with a diameter of 0.315mm. The
      attachment of the sensor to the textile is realized using a silicone film. This
      sensor configuration was characterized using a strain tester and measuring the
      resistance (extension-retraction cycles): It showed a linear resistance response
      to strain, a small hysteresis, no ageing effects and a small dependance on the
      strain velocity. The total mean error caused by all these effects was +/-5.5% in
      strain. Washing several times in a conventional washing machine did not influence
      the sensor properties. The paper finishes by showing an example application where
      21 strain sensors were integrated into a catsuit. With this garment, 27 upper
      body postures could be recognized with an accuracy of 97%.

PMID- 27879905
TI  - A Spatial-Spectral Approach for Visualization of Vegetation Stress Resulting from
      Pipeline Leakage.
AB  - Hydrocarbon leakage into the environment has large economic and environmental
      impact. Traditional methods for investigating seepages and their resulting
      pollution, such as drilling, are destructive, time consuming and expensive.
      Remote sensing is an efficient tool that offers a non-destructive investigation
      method. Optical remote sensing has been extensively tested for exploration of
      onshore hydrocarbon reservoirs and detection of hydrocarbons at the Earth's
      surface. In this research, we investigate indirect manifestations of pipeline
      leakage by way of visualizing vegetation anomalies in airborne hyperspectral
      imagery. Agricultural land-use causes a heterogeneous landcover; variation in red
      edge position between fields was much larger than infield red edge position
      variation that could be related to hydrocarbon pollution. A moving and growing
      kernel procedure was developed to normalzie red edge values relative to values of
      neighbouring pixels to enhance pollution related anomalies in the image.
      Comparison of the spatial distribution of anomalies with geochemical data
      obtained by drilling showed that 8 out of 10 polluted sites were predicted
      correctly while 2 out of 30 sites that were predicted clean were actually
      polluted.

PMID- 27879906
TI  - Comparative Analysis of EO-1 ALI and Hyperion, and Landsat ETM+ Data for Mapping
      Forest Crown Closure and Leaf Area Index.
AB  - In this study, a comparative analysis of capabilities of three sensors for
      mapping forest crown closure (CC) and leaf area index (LAI) was conducted. The
      three sensors are Hyperspectral Imager (Hyperion) and Advanced Land Imager (ALI)
      onboard EO-1 satellite and Landsat-7 Enhanced Thematic Mapper Plus (ETM+). A
      total of 38 mixed coniferous forest CC and 38 LAI measurements were collected at
      Blodgett Forest Research Station, University of California at Berkeley, USA. The
      analysis method consists of (1) extracting spectral vegetation indices (VIs),
      spectral texture information and maximum noise fractions (MNFs), (2) establishing
      multivariate prediction models, (3) predicting and mapping pixel-based CC and LAI
      values, and (4) validating the mapped CC and LAI results with field validated
      photo-interpreted CC and LAI values. The experimental results indicate that the
      Hyperion data are the most effective for mapping forest CC and LAI (CC mapped
      accuracy (MA) = 76.0%, LAI MA = 74.7%), followed by ALI data (CC MA = 74.5%, LAI
      MA = 70.7%), with ETM+ data results being least effective (CC MA = 71.1%, LAI MA
      = 63.4%). This analysis demonstrates that the Hyperion sensor outperforms the
      other two sensors: ALI and ETM+. This is because of its high spectral resolution
      with rich subtle spectral information, of its short-wave infrared data for
      constructing optimal VIs that are slightly affected by the atmosphere, and of its
      more available MNFs than the other two sensors to be selected for establishing
      prediction models. Compared to ETM+ data, ALI data are better for mapping forest
      CC and LAI due to ALI data with more bands and higher signal-to-noise ratios than
      those of ETM+ data.

PMID- 27879907
TI  - Impact of Spatial LAI Heterogeneity on Estimate of Directional Gap Fraction from
      SPOT-Satellite Data.
AB  - Directional gap probability or gap fraction is a basic parameter in the optical
      remote sensing modeling. Although some approaches have been proposed to estimate
      this gap probability from remotely sensed measurements, few efforts have been
      made to investigate the scaling effects of this parameter. This paper analyzes
      the scaling effect through aggregating the high-resolution directional gap
      probability (pixel size of 20 meters) estimated from leaf area index (LAI) images
      of VALERI database by means of Beer's law and introduces an extension of clumping
      index, C, to compensate the scaling bias. The results show that the scaling
      effect depends on both the surface heterogeneity and the nonlinearity degree of
      the retrieved function. Analytical expressions for the scaling bias of gap
      probability and C are established in function of the variance of LAI and the mean
      value of LAI in a coarse pixel. With the VALERI dataset, the study in this paper
      shows that relative scaling bias of gap probability increases with decreasing
      spatial resolution for most of land cover types. Large relative biases are found
      for most of crops sites and a mixed forest site due to their relative large
      variance of LAI, while very small biases occur over grassland and shrubs sites.
      As for C, it varies slowly in the pure forest, grassland and shrubs sites, while
      more significantly in crops and mixed forest.

PMID- 27879908
TI  - The Effect of Sea Surface Slicks on the Doppler Spectrum Width of a Backscattered
      Microwave Signal.
AB  - The influence of a surface-active substance (SAS) film on the Doppler spectrum
      width at small incidence angles is theoretically investigated for the first time
      for microwave radars with narrow-beam and knife-beam antenna patterns. It is
      shown that the requirements specified for the antenna system depend on the radar
      motion velocity. A narrow-beam antenna pattern should be used to detect slicks by
      an immobile radar, whereas radar with a knife-beam antenna pattern is needed for
      diagnostics from a moving platform. The study has revealed that the slick
      contrast in the Doppler spectrum width increases as the radar wavelength
      diminishes, thus it is preferable to utilize wavelengths not larger than 2 cm for
      solving diagnostic problems. The contrast in the Doppler spectrum width is
      generally weaker than that in the radar backscattering cross section; however,
      spatial and temporal fluctuations of the Doppler spectrum width are much weaker
      than those of the reflected signal power. This enables one to consider the
      Doppler spectrum as a promising indicator of slicks on water surface.

PMID- 27879910
TI  - An Assessment of the Altimetric Information Derived from Spaceborne SAR (RADARSAT
      1, SRTM3) and Optical (ASTER) Data for Cartographic Application in the Amazon
      Region.
AB  - Difficulties in acquiring a complete aerial photography coverage on a regular
      basis in the Brazilian Amazon due to adverse environmental conditions affect the
      quality of the national topographic database. As a consequence, topographic
      information is still poor, and when available needs to be up-dated or re-mapped.
      In this research, altimetric information derived from RADARSAT-1 (Fine and
      Standard modes), SRTM3 (3 arcseconds) and ASTER (band 3N-3B) was evaluated for
      topographic mapping in two sites located in the region: Serra dos Carajas
      (mountainous relief) and Tapajos National Forest (flat terrain). The quality of
      the information produced from Digital Elevation Models (DEMs) was evaluated
      regarding field altimetric measurements. Precise topographic field information
      acquired from Differential Global Positioning System (DGPS) was used as Ground
      Control Points (GCPs) for the modeling of the stereoscopic DEMs (RADARSAT- 1,
      ASTER) and as Independent Check Points (ICPs) for the calculation of accuracies
      of the products. The accuracies were estimated by comparison of the DEMs values
      and real elevation values given by ICPs. The analysis was performed following two
      approaches: (1) the use of Root Mean Square Error (RMSE) for the overall
      classification of the DEMs considering the Brazilian Map Accuracy Standards (PEC)
      limits and, (2) calculations of trend analysis and accuracy based on a
      methodology that takes into account computed discrepancies and standard
      deviations. The investigation has shown that for flat relief, the altimetric
      accuracy of SRTM3 and Fine RADARSAT-1 DEMs fulfilled the PEC requirements for
      1:100,000 A Class Map. However, for mountainous terrain, only the altimetry of
      SRTM3 and ASTER fulfilled these requirements. In addition, the performance of
      ASTER was slightly superior to SRTM3. However it is important to consider the
      difficulties in the acquisition of good stereo-pairs with optical data in the
      Amazon and the additional cost (GCPs) to produce ASTER DEMs. Despite showing
      systematic errors, the findings justify the usage of SRTM3 as a primary elevation
      source for semi-detailed topographic mapping in the region. It is suggested a
      combination of altimetry derived for SRTM3 and planimetry extracted from high
      resolution SAR (ALOS/PALSAR, TerraSARX, RADARSAT-2) or if available optical data
      for semi-detailed topographic mapping programs in the Brazilian Amazon, where
      terrain information is seldom available or presents low quality.

PMID- 27879909
TI  - Validation and Variation of Upper Layer Thickness in South China Sea from
      Satellite Altimeter Data.
AB  - Satellite altimeter data from 1993 to 2005 has been used to analyze the seasonal
      variation and the interannual variability of upper layer thickness (ULT) in the
      South China Sea (SCS). Base on in-situ measurements, the ULT is defined as the
      thickness from the sea surface to the depth of 16 degrees C isotherm which is
      used to validate the result derived from satellite altimeter data. In comparison
      with altimeter and in-situ derived ULTs yields a correlation coefficient of 0.92
      with a slope of 0.95 and an intercept of 6 m. The basin averaged ULT derived from
      altimeter is 160 m in winter and 171 m in summer which is similar to the in-situ
      measurements of 159 m in winter and 175 m in summer. Both results also show
      similar spatial patterns. It suggests that the sea surface height data derived
      from satellite sensors are usable for study the variation of ULT in the semi
      closed SCS. Furthermore, we also use satellite derived ULT to detect the
      development of eddy. Interannual variability of two meso-scale cyclonic eddies
      and one anticyclonic eddy are strongly influenced by El Nino events. In most
      cases, there are highly positive correlations between ULT and sea surface
      temperature except the periods of El Nino. During the onset of El Nino event, ULT
      is deeper when sea surface temperature is lower.

PMID- 27879911
TI  - Spatio-Temporal Modelling of Dust Transport over Surface Mining Areas and
      Neighbouring Residential Zones.
AB  - Projects focusing on spatio-temporal modelling of the living environment need to
      manage a wide range of terrain measurements, existing spatial data, time series,
      results of spatial analysis and inputs/outputs from numerical simulations. Thus,
      GISs are often used to manage data from remote sensors, to provide advanced
      spatial analysis and to integrate numerical models. In order to demonstrate the
      integration of spatial data, time series and methods in the framework of the GIS,
      we present a case study focused on the modelling of dust transport over a surface
      coal mining area, exploring spatial data from 3D laser scanners, GPS
      measurements, aerial images, time series of meteorological observations,
      inputs/outputs form numerical models and existing geographic resources. To
      achieve this, digital terrain models, layers including GPS thematic mapping, and
      scenes with simulation of wind flows are created to visualize and interpret coal
      dust transport over the mine area and a neighbouring residential zone. A
      temporary coal storage and sorting site, located near the residential zone, is
      one of the dominant sources of emissions. Using numerical simulations, the
      possible effects of wind flows are observed over the surface, modified by natural
      objects and man-made obstacles. The coal dust drifts with the wind in the
      direction of the residential zone and is partially deposited in this area. The
      simultaneous display of the digital map layers together with the location of the
      dominant emission source, wind flows and protected areas enables a risk
      assessment of the dust deposition in the area of interest to be performed. In
      order to obtain a more accurate simulation of wind flows over the temporary
      storage and sorting site, 3D laser scanning and GPS thematic mapping are used to
      create a more detailed digital terrain model. Thus, visualization of wind flows
      over the area of interest combined with 3D map layers enables the exploration of
      the processes of coal dust deposition at a local scale. In general, this project
      could be used as a template for dust-transport modelling which couples spatial
      data focused on the construction of digital terrain models and thematic mapping
      with data generated by numerical simulations based on Reynolds averaged Navier
      Stokes equations.

PMID- 27879912
TI  - Fabrication and Characterization of Silicon Micro-Funnels and Tapered Micro
      Channels for Stochastic Sensing Applications.
AB  - We present a simplified, highly reproducible process to fabricate arrays of
      tapered silicon micro-funnels and micro-channels using a single lithographic step
      with a silicon oxide (SiO2) hard mask on at a wafer scale. Two approaches were
      used for the fabrication. The first one involves a single wet anisotropic etch
      step in concentrated potassium hydroxide (KOH) and the second one is a combined
      approach comprising Deep Reactive Ion Etch (DRIE) followed by wet anisotropic
      etching. The etching is performed through a 500 mm thick silicon wafer, and the
      resulting structures are characterized by sharp tapered ends with a sub-micron
      cross-sectional area at the tip. We discuss the influence of various parameters
      involved in the fabrication such as the size and thickness variability of the
      substrate, dry and wet anisotropic etching conditions, the etchant composition,
      temperature, diffusion and micro-masking effects, the quality of the hard mask in
      the uniformity and reproducibility of the structures, and the importance of a
      complete removal of debris and precipitates. The presence of apertures at the tip
      of the structures is corroborated through current voltage measurements and by the
      translocation of DNA through the apertures. The relevance of the results obtained
      in this report is discussed in terms of the potential use of these structures for
      stochastic sensing.

PMID- 27879913
TI  - Computational Modeling of the Electrochemical System of Lipase Activity
      Detection.
AB  - This paper presents computational modeling of response kinetics of
      bioelectroanalytical system based on solid supported lipase substrate and lipase
      interaction. The model assumes that lipase substrate is formed by dripping and
      drying a small amount of the ethanol solution of 9-(5'
      ferrocenylpentanoyloxy)nonyl disulfide (FPONDS) and that lipase is capable of
      cleaving FPONDS ester bonds via hydrolysis mechanism. Two mathematical models
      have been developed and evaluated trough computational simulation series by
      comparing them to experimental data. The results of simulation demonstrate that a
      good fitting might be obtained only taking into account non-linear substrate wash
      off process.

PMID- 27879914
TI  - Comparing Different Approaches for Mapping Urban Vegetation Cover from Landsat
      ETM+ Data: A Case Study on Brussels.
AB  - Urban growth and its related environmental problems call for sustainable urban
      management policies to safeguard the quality of urban environments. Vegetation
      plays an important part in this as it provides ecological, social, health and
      economic benefits to a city's inhabitants. Remotely sensed data are of great
      value to monitor urban green and despite the clear advantages of contemporary
      high resolution images, the benefits of medium resolution data should not be
      discarded. The objective of this research was to estimate fractional vegetation
      cover from a Landsat ETM+ image with sub-pixel classification, and to compare
      accuracies obtained with multiple stepwise regression analysis, linear spectral
      unmixing and multi-layer perceptrons (MLP) at the level of meaningful urban
      spatial entities. Despite the small, but nevertheless statistically significant
      differences at pixel level between the alternative approaches, the spatial
      pattern of vegetation cover and estimation errors is clearly distinctive at
      neighbourhood level. At this spatially aggregated level, a simple regression
      model appears to attain sufficient accuracy. For mapping at a spatially more
      detailed level, the MLP seems to be the most appropriate choice. Brightness
      normalisation only appeared to affect the linear models, especially the linear
      spectral unmixing.

PMID- 27879915
TI  - Connecting Hazard Analysts and Risk Managers to Sensor Information.
AB  - Hazard analysts and risk managers of natural perils, such as earthquakes,
      landslides and floods, need to access information from sensor networks surveying
      their regions of interest. However, currently information about these networks is
      difficult to obtain and is available in varying formats, thereby restricting
      accesses and consequently possibly leading to decision-making based on limited
      information. As a response to this issue, state-of-the-art interoperable
      catalogues are being currently developed within the framework of the Group on
      Earth Observations (GEO) workplan. This article provides an overview of the
      prototype catalogue that was developed to improve access to information about the
      sensor networks surveying geological hazards (geohazards), such as earthquakes,
      landslides and volcanoes.

PMID- 27879916
TI  - A Lidar Point Cloud Based Procedure for Vertical Canopy Structure Analysis And 3D
      Single Tree Modelling in Forest.
AB  - A procedure for both vertical canopy structure analysis and 3D single tree
      modelling based on Lidar point cloud is presented in this paper. The whole area
      of research is segmented into small study cells by a raster net. For each cell, a
      normalized point cloud whose point heights represent the absolute heights of the
      ground objects is generated from the original Lidar raw point cloud. The main
      tree canopy layers and the height ranges of the layers are detected according to
      a statistical analysis of the height distribution probability of the normalized
      raw points. For the 3D modelling of individual trees, individual trees are
      detected and delineated not only from the top canopy layer but also from the sub
      canopy layer. The normalized points are resampled into a local voxel space. A
      series of horizontal 2D projection images at the different height levels are then
      generated respect to the voxel space. Tree crown regions are detected from the
      projection images. Individual trees are then extracted by means of a pre-order
      forest traversal process through all the tree crown regions at the different
      height levels. Finally, 3D tree crown models of the extracted individual trees
      are reconstructed. With further analyses on the 3D models of individual tree
      crowns, important parameters such as crown height range, crown volume and crown
      contours at the different height levels can be derived.

PMID- 27879917
TI  - Simultaneous Chronoamperometric Sensing of Ascorbic Acid and Acetaminophen at a
      Boron-Doped Diamond Electrode.
AB  - Cyclic voltammetry (CV) and chronoamperometry (CA) have been used to sense and
      determine simultaneously L-ascorbic acid (AA) and acetaminophen (AC) at a boron
      doped diamond electrode (BDDE) in a Britton-Robinson buffer solution. The
      calibration plots of anodic current peak versus concentration obtained from CV
      and CA data for both investigated compounds in single and di-component solutions
      over the concentration range 0.01 mM - 0.1 mM proved to be linear, with very good
      correlation parameters. Sensitivity values and RSD of 2-3% were obtained for
      various situations, involving both individual and simultaneous presence of AA and
      AC. The chronoamperometric technique associated with standard addition in
      sequential one step and/or two successive and continuous chronoamperograms at two
      characteristic potential levels represented a feasible option for the
      simultaneous determination of AA and AC in real sample systems such as
      pharmaceutical formulations. The average values indicated by the supplier were
      confirmed to a very close approximation from chronoamperomgrams by using several
      additions with the application of suitable current correction factors.

PMID- 27879918
TI  - Spatio-Temporal Analysis of Forest Fire Risk and Danger Using LANDSAT Imagery.
AB  - Computing fire danger and fire risk on a spatio-temporal scale is of crucial
      importance in fire management planning, and in the simulation of fire growth and
      development across a landscape. However, due to the complex nature of forests,
      fire risk and danger potential maps are considered one of the most difficult
      thematic layers to build up. Remote sensing and digital terrain data have been
      introduced for efficient discrete classification of fire risk and fire danger
      potential. In this study, two time-series data of Landsat imagery were used for
      determining spatio-temporal change of fire risk and danger potential in Korudag
      forest planning unit in northwestern Turkey. The method comprised the following
      two steps: (1) creation of indices of the factors influencing fire risk and
      danger; (2) evaluation of spatio-temporal changes in fire risk and danger of
      given areas using remote sensing as a quick and inexpensive means and determining
      the pace of forest cover change. Fire risk and danger potential indices were
      based on species composition, stand crown closure, stand development stage,
      insolation, slope and, proximity of agricultural lands to forest and distance
      from settlement areas. Using the indices generated, fire risk and danger maps
      were produced for the years 1987 and 2000. Spatio-temporal analyses were then
      realized based on the maps produced. Results obtained from the study showed that
      the use of Landsat imagery provided a valuable characterization and mapping of
      vegetation structure and type with overall classification accuracy higher than
      83%.

PMID- 27879919
TI  - Detecting Aquatic Vegetation Changes in Taihu Lake, China Using Multi-temporal
      Satellite Imagery.
AB  - We have measured the water quality and bio-optical parameters of 94 samples from
      Taihu Lake in situ and/or in the lab between June 10-18, 2007. A
      transparencyassisted decision tree was developed to more accurately divide the
      aquatic vegetation zone into a floating vegetation-dominated zone and a submerged
      vegetation-dominated zone, whose respective present biomass retrieval models were
      easily developed with an empirical approach because of the quasi-concurrence of
      ground field investigations with the satellite sensor flight over the lake. The
      significant quantitative relationships between the vegetation index NDVI
      (Normalized Difference Vegetation Index) of different images at different times
      were used to help develop the past biomass retrieval model on the basis of the
      present developed model. In Taihu Lake, the total covering area of aquatic
      vegetations decreased from 454.6 km2 in 2001 to 364.1 km2 in 2007.
      Correspondingly, the total biomass decreased from 489,000 tons in 2001 to 406,000
      tons in 2007, suggesting that a great change in the ecological environment has
      been taking place in Taihu Lake over this period.

PMID- 27879920
TI  - Chemical Characterization of Dew Water Collected in Different Geographic Regions
      of Poland.
AB  - The results of a dew monitoring program performed in Poland with the aim to
      outline the chemical composition of dew water in meteorological context are
      presented. Dew samples were collected from eight measurement stations from August
      2004 to November 2006. Taking into account the type of land use and
      characteristics of pollutant emission, sampling sites were divided into the
      following categories: rural, coastal urban and inland urban stations. Selected
      anions and cations as well as formaldehyde and sum of phenols were determined.
      The average TIC (Total Inorganic Ionic Content) values in dew samples ranged from
      0.83 to 3.93 between individual stations with 10.9 meq/L as the highest daily
      value of TIC measured. The average TIC values observed in dew at all stations
      were at a similar level (2.46 meq/L) when compared with hoarfrost (2.86 meq/L).
      However, these values were much higher in comparison with other kinds of
      atmospheric water like precipitation (wet only; 0.37 meq/L) or fog/cloud (1.01
      meq/L). The pH values of dew water ranged from 5.22 to 7.35 for urban coastal
      stations, from 5.67 to 8.02 for urban inland stations and from 4.16 to 8.76 for
      dew samples collected in the rural area. HCHO was found in 97 % of dew samples,
      with concentrations ranging from 0.010 to 5.40 meq/L. Excluding stations near the
      seashore, where the contribution of Na+ and Cl- increased, the most important
      ions were sulphates. A very low contribution of NO3- and noticeable increase of
      Ca2+ which were not observed in the case of precipitation and fog water, were
      typical in all stations. The contribution of ammonium ion was two times higher at
      rural stations as a result of agricultural ammonia emissions. The strongest
      correlations were noticed between the sum of acidifying anions SO42- + NO3- and
      Ca2+ ion for all urban and rural stations. A very strong correlation was also
      observed for Na+ and Cl- ions in urban coastal stations, as a natural consequence
      of the location of these stations close to the sea. It was proved that thermal
      stratification, direction of circulation and local breeze circulation control the
      atmospheric chemistry at ground level, where dew is formed. The highest TIC
      values at urban stations were associated with anticyclonic weather, while at
      rural sites with cyclonic weather situations. The chemistry of dew water in urban
      coastal stations was closely related to local breeze circulation in the warm
      season, mainly in the form of diurnal breeze causing a significant increase of
      the concentration of Na+ and Cl-ions. Thus, dew can be a good indicator of the
      atmospheric pollution level at a given site. Taking into account both high TIC
      values and the annual water equivalent estimated at around 50 mm, dew is a
      considerable factor of wet deposition, responsible for an additional 60 % of
      pollutant input into the ground when compared with precipitation.

PMID- 27879921
TI  - Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive
      Medication Alter Psychostimulant Behavior?
AB  - Neuromolecular Imaging (NMI) with novel biosensors enables the selective
      detection of neurotransmitters in vivo within seconds, on line and in real time.
      Biosensors remain in place for continuing studies over a period of months. This
      biotechnological advance is based on conventional electrochemistry; the
      biosensors detect neurotransmitters by electron transfer. Simply stated,
      biosensors adsorb electrons from each neurotransmitter at specific oxidation
      potentials; the current derived from electron transfer is proportional to
      neurotransmitter concentration. Selective electron transfer properties of these
      biosensors permit the imaging of neurotransmitters, metabolites and precursors.
      The novel BRODERICK PROBE(r) biosensors we have developed, differ in formulation
      and detection capabilities from biosensors/electrodes used in conventional
      electrochemistry/ voltammetry. In these studies, NMI, specifically, the BRODERICK
      PROBE(r) laurate biosensor images neurotransmitter signals within mesolimbic
      neuronal terminals, nucleus accumbens (NAc); dopamine (DA), serotonin (5-HT),
      homovanillic acid (HVA) and Ltryptophan (L-TP) are selectively imaged.
      Simultaneously, we use infrared photobeams to monitor open-field movement
      behaviors on line with NMI in the same animal subjects. The goals are to
      investigate integrated neurochemical and behavioral effects of cocaine and
      caffeine alone and co-administered and further, to use ketanserin to decipher
      receptor profiles for these psychostimulants, alone and co-administered. The
      rationale for selecting this medication is: ketanserin (a) is an antihypertensive
      and cocaine and caffeine produce hypertension and (b) acts at 5-HT2A/2C
      receptors, prevalent in NAc and implicated in hypertension and cocaine addiction.
      Key findings are: (a) the moderate dose of caffeine simultaneously potentiates
      cocaine's neurochemical and behavioral responses. (b) ketanserin simultaneously
      inhibits cocaine-increased DA and 5-HT release in NAc and open-field behaviors
      and (c) ketanserin inhibits 5-HT release in NAc and open-field behaviors produced
      by caffeine, but, surprisingly, acts to increase DA release in NAc. Importantly,
      the latter effect may be a possible adverse effect of the moderate dose of
      caffeine in hypertensive patients. Thus, an antihypertensive medication is shown
      here to play a role in inhibiting brain reward possibly via antihypertensive
      mechanisms at DA and 5-HT receptor subtypes within DA motor neurons. An
      explanatory note for the results obtained, is the role likely played by the G
      Protein Receptor Complex (GPRC) family of proteins. Empirical evidence shows that
      GPRC dimers, heteromers and heterotrimers may cause cross-talk between distinct
      signalling cascade pathways in the actions of cocaine and caffeine. Ligand
      directed functional selectivity, particularly for ketanserin, in addition to
      GPRCs, may also cause differential responses. The results promise new therapeutic
      strategies for drug addiction, brain reward and cardiovascular medicine.

PMID- 27879923
TI  - A Determination of Metallothionein in Larvae of Freshwater Midges (Chironomus
      riparius) Using Brdicka Reaction.
AB  - Among wide spectrum of biomolecules induced by various stress factors low
      molecular mass protein called metallothionein (MT) is suitable for assessment of
      the heavy metal environmental pollution. The aim of this work was to determine
      the metallothionein and total thiols content in larvae of freshwater midges
      (Chironomus riparius) sampled from laboratory exposure to cadmium(II) ions and
      from field studies using differential pulse voltammetry Brdicka reaction. Unique
      electrochemical instrument, stationary electrochemical analyser Autolab coupled
      with autosampler, was utilized for the analysis of the samples. The detection
      limit for MT was evaluated as 5 nM. The larvae exposed to two doses (50 ng/g or
      50 MUg/g) of cadmium(II) ions for fifteen days under laboratory controlled
      conditions were at the end of the exposure killed, homogenized and analysed. MT
      content in control samples was 1.2 MUM, in larvae exposed to 50 ng Cd/g it was
      2.0 MUM and in larvae exposed to 50 MUg Cd/g 2.9 MUM. Moreover at field study
      chironomid larvae as well as sediment samples have been collected from eight
      field sites with different levels of pollution by heavy. The metals content
      (chromium, nickel, copper, zinc, arsenic, molybdenum, cadmium, tin and lead) in
      the sediment and or MT content in the chironomid larvae were determined by
      inductively coupled plasma mass spectrometry or Brdicka reaction, respectively.

PMID- 27879922
TI  - Bacterial Biosensors for Measuring Availability of Environmental Pollutants.
AB  - Traditionally, pollution risk assessment is based on the measurement of a
      pollutant's total concentration in a sample. The toxicity of a given pollutant in
      the environment, however, is tightly linked to its bioavailability, which may
      differ significantly from the total amount. Physico-chemical and biological
      parameters strongly influence pollutant fate in terms of leaching, sequestration
      and biodegradation. Bacterial sensorreporters, which consist of living micro
      organisms genetically engineered to produce specific output in response to target
      chemicals, offer an interesting alternative to monitoring approaches. Bacterial
      sensor-reporters detect bioavailable and/or bioaccessible compound fractions in
      samples. Currently, a variety of environmental pollutants can be targeted by
      specific biosensor-reporters. Although most of such strains are still confined to
      the lab, several recent reports have demonstrated utility of bacterial sensing
      reporting in the field, with method detection limits in the nanomolar range. This
      review illustrates the general design principles for bacterial sensor-reporters,
      presents an overview of the existing biosensor-reporter strains with emphasis on
      organic compound detection. A specific focus throughout is on the concepts of
      bioavailability and bioaccessibility, and how bacteria-based sensing-reporting
      systems can help to improve our basic understanding of the different processes at
      work.

PMID- 27879924
TI  - Comparison of Mercury Distribution Between Liver and Muscle - A Biomonitoring of
      Fish from Lightly and Heavily Contaminated Localities.
AB  - Tissue samples from 1,117 fish of 25 species were collected from 1991 through
      1996 at 13 locations along the River Elbe. The principal indicator species were
      perch (Perca fluviatilis) (n=118), chub (Leuciscus cephalus L.) (n=113) and roach
      (Rutilus rutilus) (n=138). Mercury (Hg) concentrations in muscle and liver were
      determined by atomic absorption spectrometry. The liver/muscle index in three
      indicator species from heavily contaminated and lightly contaminated localities
      were significantly different. In fish from heavily contaminated localities, Hg
      was deposited preferentially in the liver (the depository for inorganic and
      organic forms of Hg), while in lightly contaminated areas, it was deposited
      preferentially in muscle.

PMID- 27879925
TI  - Development of Amperometric Hydrogen Peroxide Sensor Based on Horseradish
      Peroxidase-Immobilized Poly(Thiophene-co-EpoxyThiophene).
AB  - A modified electrode for hydrogen peroxide (H2O2) sensing was prepared via
      thiophene (Th) with epoxy group. Thiophene (EpoxyTh) with epoxy group was
      synthesized by reaction of 3-bromothiophene and glycidyl methacrylate (GMA) in
      acetonitrile according to Heck Reaction. The electrocopolymerization of Th and
      EpoxyTh was performed on the surface of indium tin oxide (ITO) electrode by
      cycling the potential between -1.0 and +2.5 V in mixture of thiophene (Th) and
      EpoxyTh. Poly(Th-co- EpoxyTh) grown onto the ITO electrode was successfully
      confirmed by SEM, AFM, and water contact angle analysis, respectively. Finally,
      the HRP was immobilized on the surface of poly(Th-co-EpoxyTh) electrode by
      covalent binding. The amperometric response of the HRP-immobilized poly(Th-co
      EpoxyTh) electrode for H2O2 was examined by cyclic voltammetry (CV). The HRP
      immobilized poly(Th-co-EpoxyTh) electrode showed linearity from 0.1 to 30 mM
      H2O2, good reproducibility, and long life time.

PMID- 27879926
TI  - A Methodology to Validate the InSAR Derived Displacement Field of the September
      7th, 1999 Athens Earthquake Using Terrestrial Surveying. Improvement of the
      Assessed Deformation Field by Interferometric Stacking.
AB  - The primary objective of this paper is the evaluation of the InSAR derived
      displacement field caused by the 07/09/1999 Athens earthquake, using as reference
      an external data source provided by terrestrial surveying along the Mornos river
      open aqueduct. To accomplish this, a processing chain to render comparable the
      leveling measurements and the interferometric derived measurements has been
      developed. The distinct steps proposed include a solution for reducing the
      orbital and atmospheric interferometric fringes and an innovative method to
      compute the actual InSAR estimated vertical ground subsidence, for direct
      comparison with the leveling data. Results indicate that the modeled deformation
      derived from a series of stacked interferograms, falls entirely within the
      confidence interval assessed for the terrestrial surveying data.

PMID- 27879927
TI  - Satellite Assessment of Bio-Optical Properties of Northern Gulf of Mexico Coastal
      Waters Following Hurricanes Katrina and Rita.
AB  - The impacts of major tropical storms events on coastal waters include sediment
      resuspension, intense water column mixing, and increased delivery of terrestrial
      materials into coastal waters. We examined satellite imagery acquired by the
      Moderate Resolution Imaging Spectroradiometer (MODIS) ocean color sensor aboard
      the Aqua spacecraft following two major hurricane events: Hurricane Katrina,
      which made landfall on 29 August 2005, and Hurricane Rita, which made landfall on
      24 September. MODIS Aqua true color imagery revealed high turbidity levels in
      shelf waters immediately following the storms indicative of intense resuspension.
      However, imagery following the landfall of Katrina showed relatively rapid return
      of shelf water mass properties to pre-storm conditions. Indeed, MODIS Aqua
      derived estimates of diffuse attenuation at 490 nm (K_490) and chlorophyll
      (chlor_a) from mid-August prior to the landfall of Hurricane Katrina were
      comparable to those observed in mid-September following the storm. Regions of
      elevated K_490 and chlor_a were evident in offshore waters and appeared to be
      associated with cyclonic circulation (cold-core eddies) identified on the basis
      of sea surface height anomaly (SSHA). Imagery acquired shortly after Hurricane
      Rita made landfall showed increased water column turbidity extending over a large
      area of the shelf off Louisiana and Texas, consistent with intense resuspension
      and sediment disturbance. An interannual comparison of satellite-derived
      estimates of K_490 for late September and early October revealed relatively lower
      levels in 2005, compared to the mean for the prior three years, in the vicinity
      of the Mississippi River birdfoot delta. In contrast, levels above the previous
      three year mean were observed off Texas and Louisiana 7-10 d after the passage of
      Rita. The lower values of K_490 near the delta could be attributed to relatively
      low river discharge during the preceding months of the 2005 season. The elevated
      levels off Texas and Louisiana were speculated to be due to the presence of fine
      grain sediment or dissolved materials that remained in the water column following
      the storm, and may also have been associated with enhanced phytoplankton biomass
      stimulated by the intense vertical mixing and offshore delivery of shelf water
      and associated nutrients. This latter view was supported by observations of high
      chlor_a in association with regions of cyclonic circulation.

PMID- 27879928
TI  - Integrating Physical and Topographic Information Into a Fuzzy Scheme to Map
      Flooded Area by SAR.
AB  - A flood mapping procedure based on a fuzzy sets theory has been developed. The
      method is based on the integration of Synthetic Aperture Radar (SAR) measurements
      with additional data on the inundated area, such as a land cover map and a
      digital elevation model (DEM). The information on land cover has allowed us to
      account for both specular reflection, typical of open water, and double bounce
      backscattering, typical of forested and urban areas. DEM has been exploited to
      include simple hydraulic considerations on the dependence of inundation
      probability on surface characteristics. Contextual information has been taken
      into account too. The proposed algorithm has been tested on a flood occurred in
      Italy on November 1994. A pair of ERS-1 images, collected before and after (three
      days later) the flood, has been used. The results have been compared with the
      data provided by a ground survey carried out when the flood reached its maximum
      extension. Despite the temporal mismatch between the survey and the post
      inundation SAR image, the comparison has yielded encouraging results, with the
      87% of the pixels correctly classified as inundated.

PMID- 27879929
TI  - Optical Algorithms at Satellite Wavelengths for Total Suspended Matter in
      Tropical Coastal Waters.
AB  - Is it possible to derive accurately Total Suspended Matter concentration or its
      proxy, turbidity, from remote sensing data in tropical coastal lagoon waters? To
      investigate this question, hyperspectral remote sensing reflectance, turbidity
      and chlorophyll pigment concentration were measured in three coral reef lagoons.
      The three sites enabled us to get data over very diverse environments:
      oligotrophic and sediment-poor waters in the southwest lagoon of New Caledonia,
      eutrophic waters in the Cienfuegos Bay (Cuba), and sediment-rich waters in the
      Laucala Bay (Fiji). In this paper, optical algorithms for turbidity are presented
      per site based on 113 stations in New Caledonia, 24 stations in Cuba and 56
      stations in Fiji. Empirical algorithms are tested at satellite wavebands useful
      to coastal applications. Global algorithms are also derived for the merged data
      set (193 stations). The performances of global and local regression algorithms
      are compared. The best one-band algorithms on all the measurements are obtained
      at 681 nm using either a polynomial or a power model. The best two-band
      algorithms are obtained with R412/R620, R443/R670 and R510/R681. Two three-band
      algorithms based on Rrs620.Rrs681/Rrs412 and Rrs620.Rrs681/Rrs510 also give fair
      regression statistics. Finally, we propose a global algorithm based on one or
      three bands: turbidity is first calculated from Rrs681 and then, if < 1 FTU, it
      is recalculated using an algorithm based on Rrs620.Rrs681/Rrs412. On our data
      set, this algorithm is suitable for the 0.2-25 FTU turbidity range and for the
      three sites sampled (mean bias: 3.6 %, rms: 35%, mean quadratic error: 1.4 FTU).
      This shows that defining global empirical turbidity algorithms in tropical
      coastal waters is at reach.

PMID- 27879930
TI  - Kernel Based Nonlinear Dimensionality Reduction and Classification for Genomic
      Microarray.
AB  - Genomic microarrays are powerful research tools in bioinformatics and modern
      medicinal research because they enable massively-parallel assays and simultaneous
      monitoring of thousands of gene expression of biological samples. However, a
      simple microarray experiment often leads to very high-dimensional data and a huge
      amount of information, the vast amount of data challenges researchers into
      extracting the important features and reducing the high dimensionality. In this
      paper, a nonlinear dimensionality reduction kernel method based locally linear
      embedding(LLE) is proposed, and fuzzy K-nearest neighbors algorithm which
      denoises datasets will be introduced as a replacement to the classical LLE's KNN
      algorithm. In addition, kernel method based support vector machine (SVM) will be
      used to classify genomic microarray data sets in this paper. We demonstrate the
      application of the techniques to two published DNA microarray data sets. The
      experimental results confirm the superiority and high success rates of the
      presented method.

PMID- 27879931
TI  - Determination of Lamotrigine in Pharmaceutical Preparations by Adsorptive
      Stripping Voltammetry Using Screen Printed Electrodes.
AB  - This paper describes a procedure that has been optimized for the determination of
      lamotrigine by Differential Pulse Adsorptive Stripping Voltammetry (DPAdSV) using
      carbon screen-printed electrodes (CSPE) and mercury coated carbon screen-printed
      electrodes. Selection of the experimental parameters was made using experimental
      design methodology. The detection limit found was 5.0 x 10-6 M and 2.0 x 10-6 M
      for the non modified and Hg modified CSPE, respectively. In terms of
      reproducibility, the precision of the above mentioned methods was calculated in
      %RSD values at 9.83% for CSPE and 2.73% for Hg-CSPE. The Hg-coated CSPEs
      developed in this work were successfully applied in the determination of
      lamotrigine in pharmaceutical preparations.

PMID- 27879932
TI  - On the Soil Roughness Parameterization Problem in Soil Moisture Retrieval of Bare
      Surfaces from Synthetic Aperture Radar.
AB  - Synthetic Aperture Radar has shown its large potential for retrieving soil
      moisture maps at regional scales. However, since the backscattered signal is
      determined by several surface characteristics, the retrieval of soil moisture is
      an ill-posed problem when using single configuration imagery. Unless accurate
      surface roughness parameter values are available, retrieving soil moisture from
      radar backscatter usually provides inaccurate estimates. The characterization of
      soil roughness is not fully understood, and a large range of roughness parameter
      values can be obtained for the same surface when different measurement
      methodologies are used. In this paper, a literature review is made that
      summarizes the problems encountered when parameterizing soil roughness as well as
      the reported impact of the errors made on the retrieved soil moisture. A number
      of suggestions were made for resolving issues in roughness parameterization and
      studying the impact of these roughness problems on the soil moisture retrieval
      accuracy and scale.

PMID- 27879933
TI  - Short-term Influences on Suspended Particulate Matter Distribution in the
      Northern Gulf of Mexico: Satellite and Model Observations.
AB  - Energetic meteorological events such as frontal passages and hurricanes often
      impact coastal regions in the northern Gulf of Mexico that influence geochemical
      processes in the region. Satellite remote sensing data such as winds from
      QuikSCAT, suspended particulate matter (SPM) concentrations derived from SeaWiFS
      and the outputs (sea level and surface ocean currents) of a nested navy coastal
      ocean model (NCOM) were combined to assess the effects of frontal passages
      between 23-28 March 2005 on the physical properties and the SPM characteristics
      in the northern Gulf of Mexico. Typical changes in wind speed and direction
      associated with frontal passages were observed in the latest 12.5 km wind product
      from QuikSCAT with easterly winds before the frontal passage undergoing
      systematic shifts in direction and speed and turning northerly, northwesterly
      during a weak and a strong front on 23 and 27 March, respectively. A quantitative
      comparison of model sea level results with tide gauge observations suggest better
      correlations near the delta than in the western part of the Gulf with elevated
      sea levels along the coast before the frontal passage and a large drop in sea
      level following the frontal passage on 27 March. Model results of surface
      currents suggested strong response to wind forcing with westward and onshore
      currents before the frontal passage reversing into eastward, southeastward
      direction over a six day period from 23 to 28 March 2005. Surface SPM
      distribution derived from SeaWiFS ocean color data for two clear days on 23 and
      28 March 2005 indicated SPM plumes to be oriented with the current field with
      increasing concentrations in nearshore waters due to resuspension and discharge
      from the rivers and bays and its seaward transport following the frontal passage.
      The backscattering spectral slope gamma, a parameter sensitive to particle size
      distribution also indicated lower gamma values (larger particles) in nearshore
      waters that decreased offshore (smaller particles). The use of both satellite and
      model results revealed the strong interactions between physical processes and the
      surface particulate field in response to the frontal passage in a large
      riverdominated coastal margin.

PMID- 27879934
TI  - Cross-Layer Adaptive Feedback Scheduling of Wireless Control Systems.
AB  - There is a trend towards using wireless technologies in networked control
      systems. However, the adverse properties of the radio channels make it difficult
      to design and implement control systems in wireless environments. To attack the
      uncertainty in available communication resources in wireless control systems
      closed over WLAN, a cross-layer adaptive feedback scheduling (CLAFS) scheme is
      developed, which takes advantage of the co-design of control and wireless
      communications. By exploiting crosslayer design, CLAFS adjusts the sampling
      periods of control systems at the application layer based on information about
      deadline miss ratio and transmission rate from the physical layer. Within the
      framework of feedback scheduling, the control performance is maximized through
      controlling the deadline miss ratio. Key design parameters of the feedback
      scheduler are adapted to dynamic changes in the channel condition. An eventdriven
      invocation mechanism for the feedback scheduler is also developed. Simulation
      results show that the proposed approach is efficient in dealing with channel
      capacity variations and noise interference, thus providing an enabling technology
      for control over WLAN.

PMID- 27879935
TI  - Detection of Carcinoembryonic Antigens Using a Surface Plasmon Resonance
      Biosensor.
AB  - Carcinoembryonic antigen (CEA) is an oncofoetal cell-surface glycoprotein that
      serves as an important tumor marker for colorectal and some other carcinomas. In
      this work, a CEA immunoassay using a surface plasmon resonance (SPR) biosensor
      has been developed. SPR could provide label-free, real-time detection with high
      sensitivity, though its ability to detect CEA in human serum was highly dependent
      on the analytical conditions employed. We investigated the influences of various
      analytical conditions including immobilization methods for anti-CEA antibody and
      composition of sensor surface on the selective and sensitive detection of CEA.
      The results show that anti-CEA antibody immobilized via Protein A or Protein G
      caused a large increase in the resonance signal upon injection of human serum due
      to the interactions with IgGs in serum, while direct covalent immobilization of
      anti-CEA antibody could substantially reduce it. An optimized protocol based on
      further kinetic analysis and the use of 2nd and 3rd antibodies for the sandwich
      assay allowed detecting spiked CEA in human serum as low as 25 ng/mL.
      Furthermore, a self-assembled monolayer of mixed ethylene-glycol terminated
      alkanethiols on gold was found to have a comparable ability in detecting CEA as
      CM5 with thick dextran matrix and C1 with short flat layer on gold.

PMID- 27879936
TI  - Protein Detection with Aptamer Biosensors.
AB  - Aptamers have been developed for different applications. Their use as new
      biological recognition elements in biosensors promises progress for fast and easy
      detection of proteins. This new generation of biosensor (aptasensors) will be
      more stable and well adapted to the conditions of real samples because of the
      specific properties of aptamers.

PMID- 27879937
TI  - A Fixed-Threshold Approach to Generate High-Resolution Vegetation Maps for IKONOS
      Imagery.
AB  - Vegetation distribution maps from remote sensors play an important role in urban
      planning, environmental protecting and related policy making. The normalized
      difference vegetation index (NDVI) is the most popular approach to generate
      vegetation maps for remote sensing imagery. However, NDVI is usually used to
      generate lower resolution vegetation maps, and particularly the threshold needs
      to be chosen manually for extracting required vegetation information. To tackle
      this threshold selection problem for IKONOS imagery, a fixed-threshold approach
      is developed in this work, which integrates with an extended Tasseled Cap
      transformation and a designed image fusion method to generate high-resolution (1
      meter) vegetation maps. Our experimental results are promising and show it can
      generate more accurate and useful vegetation maps for IKONOS imagery.

PMID- 27879938
TI  - Textile Pressure Sensor Made of Flexible Plastic Optical Fibers.
AB  - In this paper we report the successful development of pressure sensitive textile
      prototypes based on flexible optical fibers technology. Our approach is based on
      thermoplastic silicone fibers, which can be integrated into woven textiles. As
      soon as pressure at a certain area of the textile is applied to these fibers they
      change their cross section reversibly, due to their elastomeric character, and a
      simultaneous change in transmitted light intensity can be detected. We have
      successfully manufactured two different woven samples with fibers of 0.51 and
      0.98 mm diameter in warp and weft direction, forming a pressure sensitive matrix.
      Determining their physical behavior when a force is applied shows that pressure
      measurements are feasible. Their usable working range is between 0 and 30 N.
      Small drifts in the range of 0.2 to 4.6%, over 25 load cycles, could be measured.
      Finally, a sensor array of 2 x 2 optical fibers was tested for sensitivity,
      spatial resolution and light coupling between fibers at intersections.

PMID- 27879940
TI  - The Image Transceiver Device: Studies of Improved Physical Design.
AB  - The Image Transceiver Device (ITD) design is based on combining LCOS micro
      display, image processing tools and back illuminated APS imager in single CMOS
      chip [1]. The device is under development for Head-Mounted Display applications
      in augmented and virtual reality systems. The main issues with the present design
      are a high crosstalk of the backside imager and the need to shield the pixel
      circuitry from the photocharges generated in the silicon substrate. In this
      publication we present a modified, "deep p-well" ITD pixel design, which provides
      a significantly reduced crosstalk level, as well as an effective shielding of
      photo-charges for the pixel circuitry. The simulation performed using Silvaco
      software [ATLAS Silicon Device Simulator, Ray Trace and Light Absorption
      programs, Silvaco International, 1998] shows that the new approach provides high
      photo response and allows increasing the optimal thickness of the die over and
      above the 10-15 micrometers commonly used for back illuminated imaging devices,
      thereby improving its mechanical ruggedness following the thinning process and
      also providing a more efficient absorption of the long wavelength photons. The
      proposed deep p-well pixel structure is also a technology solution for the
      fabrication of high performance back illuminated CMOS image sensors.

PMID- 27879939
TI  - Electrochemical Sensing and Assessment of Parabens in Hydro- Alcoholic Solutions
      and Water Using a Boron-Doped Diamond Electrode.
AB  - In this paper, the electrochemical behaviour of several parabens preservatives,
      i.e. esters of p-hydroxybenzoic acid, methyl-, ethyl- and propyl-4
      hydroxybenzoates as methyl-, ethyl- and propyl-parabens (MB, EB, and PB), has
      been investigated at a commercial boron-doped diamond electrode (BDDE),
      especially in the anodic potential range, in both hydro-alcoholic and aqueous
      media. The cyclic voltammetric and chronoamperometric measurements yielded
      calibration plots with very good linearity (R2 between 0.990 and 0.998) and high
      sensitivity, useful for detection and analytical applications. The determination
      of the characteristics of individual compounds, of an "overall paraben index",
      the assessment of the stability and the saturation solubility in water, and the
      amperometric sensing and determination in double distilled, tap and river water
      matrix of the relatively slightly soluble investigated parabens have been carried
      out using electrochemical alternative. Estimated water solubility was correlated
      with the octanol-water partition coefficient. Several ideas regarding stability
      and persistence of the presumptive eco-toxic investigated preservatives in the
      environment or water systems have been adjacently discussed.

PMID- 27879941
TI  - Detection of Hidden Hostile/Terrorist Groups in Harsh Territories by Using
      Animals as Mobile Biological Sensors.
AB  - Terrorism is the greatest threat to national security and cannot be defeated by
      conventional military force alone. In critical areas such as Iraq, Afghanistan
      and Turkey, regular forces cannot reach these hostile/terrorist groups, the
      instigators of terrorism. These groups have a clear understanding of the relative
      ineffectiveness of counter-guerrilla operations and rely on guerrilla warfare to
      avoid major combat as their primary means of continuing the conflict with the
      governmental structures. In Internal Security Operations, detection of terrorist
      and hostile groups in their hiding places such as caves, lairs, etc. can only be
      achieved by professionally trained people such as Special Forces or intelligence
      units with the necessary experience and tools suitable for collecting accurate
      information in these often harsh, rugged and mountainous countries. To assist
      these forces, commercial micro-sensors with wireless interfaces could be utilized
      to study and monitor a variety of phenomena and environments from a certain
      distance for military purposes. In order to locate hidden terrorist groups and
      enable more effective use of conventional military resources, this paper proposes
      an active remote sensing model implanted into animals capable of living in these
      environments. By using these mobile sensor devices, improving communications for
      data transfer from the source, and developing better ways to monitor and detect
      threats, terrorist ability to carry out attacks can be severely disrupted.

PMID- 27879943
TI  - PAU/RAD: Design and Preliminary Calibration Results of a New L-Band Pseudo
      Correlation Radiometer Concept.
AB  - The Passive Advanced Unit (PAU) for ocean monitoring is a new type of instrument
      that combines in a single receiver and without time multiplexing, a polarimetric
      pseudo-correlation microwave radiometer at L-band (PAU-RAD) and a GPS
      reflectometer (PAU-GNSS/R). These instruments in conjunction with an infra-red
      radiometer (PAU-IR) will respectively provide the sea surface temperature and the
      sea state information needed to accurately retrieve the sea surface salinity from
      the radiometric measurements. PAU will consist of an array of 4x4 receivers
      performing digital beamforming and polarization synthesis both for PAU-RAD and
      PAU-GNSS/R. A concept demonstrator of the PAU instrument with only one receiver
      has been implemented (PAU-One Receiver or PAU-OR). PAU-OR has been used to test
      and tune the calibration algorithms that will be applied to PAU. This work
      describes in detail PAU-OR's radiometer calibration algorithms and their
      performance.

PMID- 27879942
TI  - ST Quartz Acoustic Wave Sensors with Sectional Guiding Layers.
AB  - We report the effect of removing a section of guiding layer from the propagation
      paths of ST-quartz Love wave sensors; this offers the ease of fabrication of a
      polymer guiding layer whilst retaining the native surface of the quartz which may
      then be used for the attachment of a sensitizing layer. Data is presented for the
      rigid and viscous loading, which indicates a small reduction in mass sensitivity
      compared to a Love wave device. Biosensing capabilities of these discontinuous
      'sectional' guiding layer devices are demonstrated using protein adsorption from
      solution.

PMID- 27879944
TI  - Nanobioengineering and Characterization of a Novel Estrogen Receptor Biosensor.
AB  - We constructed an original supramolecular assembly on a surface of sensor
      composed of an innovative combination of an engineered cytochrome b5 and a
      modified nucleic acid bound to a synthetic lipid hemimembrane. The protein/DNA
      block, called (PDNA) 2, was synthesized and purified before its immobilization
      onto a hybrid bilayer reconstituted on a gold surface. Surface plasmon resonance
      (SPR) and atomic force microscopy (AFM) were engaged in parallel on the same
      substrates in order to better understand dynamic events that occur at the surface
      of the biosensor. Good correlations were obtained in terms of specificity and
      reversibility. These findings allow us to present a first application of such
      biosensor in the study of the interaction processes between nuclear receptor and
      DNA.

PMID- 27879945
TI  - Multi-Source Remotely Sensed Data Combination: Projection Transformation Gap-Fill
      Procedure.
AB  - In this work a new gap-fill technique entitled projection transformation has been
      developed and used for filling missed parts of remotely sensed imagery. In
      general techniques for filling missed area of an image are broken down into three
      main categories: multi-source techniques that take the advantages of other data
      sources (e.g. using cloud free images to reconstruct the cloudy areas of other
      images); the second ones fabricate the gap areas using non-gapped parts of an
      image itself, this group of techniques are referred to as single-source gap-fill
      procedures; and third group contains methods that make up a combination of both
      mentioned techniques, therefore they are called hybrid gap-fill procedures. Here
      a new developed multi-source methodology called projection transformation for
      filling a simulated gapped area in the Landsat7/ETM+ imagery is introduced. The
      auxiliary imagery to filling the gaps is an earlier obtained L7/ETM+ imagery.
      Ability of the technique was evaluated from three points of view: statistical
      accuracy measuring, visual comparison, and post classification accuracy
      assessment. These evaluation indicators are compared to the results obtained from
      a commonly used technique by the USGS as Local Linear Histogram Matching (LLHM)
      [1]. Results show the superiority of our technique over LLHM in almost all
      aspects of accuracy.

PMID- 27879946
TI  - Integrating Remote Sensing Information Into A Distributed Hydrological Model for
      Improving Water Budget Predictions in Large-scale Basins through Data
      Assimilation.
AB  - This paper investigates whether remote sensing evapotranspiration estimates can
      be integrated by means of data assimilation into a distributed hydrological model
      for improving the predictions of spatial water distribution over a large river
      basin with an area of 317,800 km2. A series of available MODIS satellite images
      over the Haihe River basin in China are used for the year 2005.
      Evapotranspiration is retrieved from these 1*1 km resolution images using the
      SEBS (Surface Energy Balance System) algorithm. The physically-based distributed
      model WEP-L (Water and Energy transfer Process in Large river basins) is used to
      compute the water balance of the Haihe River basin in the same year. Comparison
      between model-derived and remote sensing retrieval basin-averaged
      evapotranspiration estimates shows a good piecewise linear relationship, but
      their spatial distribution within the Haihe basin is different. The remote
      sensing derived evapotranspiration shows variability at finer scales. An extended
      Kalman filter (EKF) data assimilation algorithm, suitable for non-linear
      problems, is used. Assimilation results indicate that remote sensing observations
      have a potentially important role in providing spatial information to the
      assimilation system for the spatially optical hydrological parameterization of
      the model. This is especially important for large basins, such as the Haihe River
      basin in this study. Combining and integrating the capabilities of and
      information from model simulation and remote sensing techniques may provide the
      best spatial and temporal characteristics for hydrological states/fluxes, and
      would be both appealing and necessary for improving our knowledge of fundamental
      hydrological processes and for addressing important water resource management
      problems.

PMID- 27879947
TI  - Cantilever measurements of surface stress, surface reconstruction, film stress
      and magnetoelastic stress of monolayers.
AB  - We review the application of cantilever-based stress measurements in surface
      science and magnetism. The application of thin (thickness appr. 0.1 mm) single
      crystalline substrates as cantilevers has been used successfully to measure
      adsorbate-induced surface stress changes, lattice misfit induced film stress, and
      magneto-elastic stress of ferromagnetic monolayers. Surface stress changes as
      small as 0.01 N/m can be readily measured, and this translates into a sensitivity
      for adsorbate-coverage well below 0.01 of one layer. Stress as large as several
      GPa, beyond the elasticity limits of high strength materials, is measured, and it
      is ascribed to the lattice misfit between film and substrate. Our results point
      at the intimate relation between surface stress and surface reconstruction,
      stress-induced structural changes in epitaxially strained films, and strain
      induced modifications of the magneto-elastic coupling in ferromagnetic
      monolayers.

PMID- 27879948
TI  - WITHDRAWN: Efficacy and local tolerability of different spray products in the
      treatment of mild to moderate acne of the back and chest. A controlled, 3-arm,
      assessor-blinded prospective trial.
AB  - AHEAD OF PRINT ARTICLE WITHDRAWN BY PUBLISHER.

PMID- 27879949
TI  - Single-center experience with vascular closure devices in real-world endovascular
      peripheral interventions.
AB  - BACKGROUND: The aim of the current study was to evaluate the efficacy and safety
      of vascular closure devices (VCDs) in non-cardiac endovascular interventions.
      METHODS: Retrospective analysis of consecutive patients submitted to endovascular
      interventions, with deployment of 2327 vascular closure devices. Demographic,
      clinical/periprocedural, post-operative, complication and reintervention data
      were reviewed. RESULTS: A total of 2107 patients (1409 [66.9%] men) were
      included. Perclose ProGlide(r) (Abbott Vascular) was employed 1683 times (72.3%),
      Angio-SealTM (St. Jude Medical Inc.) 463 (19.9%) and 181 (7.8%) Exoseal(r)
      (Cordis). Patients were 70.4+/-11 years old. Of all vascular approaches, 1794
      were retrograde (77.1%) and 533 antegrade (22.9%), with sheath size ranging from
      5 to 8 French. Overall success rate was 95.2% and did not significantly vary
      according to the device. Overall failure rate was 4.8%, with high puncture site,
      morbid obesity, previous total anticoagulation and severe calcification being
      related to worse efficiency results. Major complications occurred in 15 patients
      (0.6%). All patients were evaluated before discharge from the hospital, and were
      scheduled to return for ambulatory follow-up visits at 30 days postoperatively.
      Control duplex ultrasonography was performed on a regular basis, or within this
      period in case of clinical complain/signs. CONCLUSIONS: Vascular closure devices
      proved to be safe and effective in this study. Additional prospective randomized
      studies are recommended.

PMID- 27879950
TI  - Systematic review of follow-up compliance after endovascular abdominal aortic
      aneurysm repair.
AB  - INTRODUCTION: Lifelong surveillance after endovascular aortic aneurysm repair
      (EVAR) is recommended to monitor the effectiveness and durability of the
      treatment. The aim of this study was to assess patients' compliance with the
      follow-up imaging protocol, the presence of any factors associated with
      compliance and the potential influence of imaging-protocol adherence on outcomes.
      EVIDENCE ACQUISITION: MEDLINE, EMBASE, and Cochrane Central databases and key
      references were searched. EVIDENCE SYNTHESIS: One multicenter observational study
      (registry) and nine retrospective studies were identified reporting on EVAR
      surveillance compliance. The studies included 36,119 patients with mean age of
      76+/-3.1 years under mean follow-up ranging from 25 to 73 months. Most of them
      were males (51-89%), white (51-97.7%) and the majority of them were living over
      100 miles from the treatment center. The data were too heterogeneous to perform a
      meta-analysis. Incomplete follow-up and complete loss of follow-up were ranging
      from 15% to 65% and 22% to 56%, respectively. Advanced age, symptomatic or
      ruptured aneurysm, history of chronic diseases, and social-economic factors were
      associated with poor follow-up compliance. Five studies suggested that complete
      follow-up did not offer any survival benefit, while only one study suggested that
      incomplete follow-up was associated with higher fatal complication rates.
      CONCLUSIONS: Patients' compliance with follow-up protocol after EVAR is about
      50%. Several factors have been associated with this poor compliance, however
      there is lack of solid evidence to show that this poor compliance results in
      worse outcomes. Prospective studies focusing on follow-up adherence are needed in
      order to evaluate its impact on the outcomes.

PMID- 27879951
TI  - Multidisciplinary management of Spontaneous Spinal Infections: there is a
      correlation between timing, type of treatment and outcome? A multivariate
      analysis of an observational cohort study.
AB  - BACKGROUND: Spontaneous Spinal Infections SSI represent a rare and serious
      pathological entity. We've tried to study a correlation between type of
      treatment, timing of treatment and clinical outcome through a multivariate
      analysis of an observational cohort study with the aim to define what is the
      optimal clinico-therapeutic management. METHODS: We perform a retrospective
      observational cohort study on all consecutive patients observed in our Institute
      in a period of 13 years; From 2001 to 2014 we enrolled 50 consecutive patients
      with symptomatic spontaneous spinal infections (no previous surgery or recent
      infection in other site), confirmed with diagnostic imaging. The inclusion
      parameters were: diagnostic imaging, signs and symptoms positive for SSI, no
      history of recent infection or surgery. Of each parameter analyzed, we've
      calculated mean and standard deviation and when necessary correlation (rho),
      covariance and relation coefficient between type of treatment, timing of
      treatment and clinical outcome. RESULTS: Our results suggest that an increase of
      one day from the onset of symptoms and the start of therapy leads to an increase
      in the ODI scale both at 6 months than at 1 year, with a statistical relevance,
      so our experience shows a statistically significant correlation and a positive co
      variance between timing and outcome at 6 months and 1 year. CONCLUSIONS: SSI are
      rare, very difficult to diagnose and represent a significant clinical problem. If
      not properly managed, may lead to significant impact in the quality of life. The
      most relevant problem is not the treatment, conservative or surgical, but early
      diagnosis, so a careful physical, laboratory and imaging examination is
      fundamental, with an important help provided by isolation of the pathogen and
      histology. In our experience early diagnosis has a fundamental role. In the light
      of this, current treatment protocols may require a prompt and multidisciplinary
      management including infectivologists, neuroradiologists and spine surgeons.

PMID- 27879952
TI  - Allograft versus autograft in cervical and lumbar spinal fusions: an examination
      of operative time, length of stay, surgical site infection, and blood
      transfusions.
AB  - BACKGROUND: Autograft harvesting for spine arthrodesis has been associated with
      longer operative times and increased blood loss. Allograft compared to autograft
      in spinal fusions has not been studied in a multicenter cohort. METHODS: Patients
      enrolled in the ACS-NSQIP registry between 2012 and 2013 who underwent cervical
      or lumbar spinal fusion with either allograft or autograft through a separate
      incision were included for analysis. The primary outcomes of interest were
      operative time, length of stay, blood transfusion, and surgical site infection
      (SSI). RESULTS: A total of 6,790 and 6,718 patients received a cervical or lumbar
      spinal fusion, respectively. On unadjusted analysis in both cervical and lumbar
      cohorts, autograft was associated with increased rates of blood transfusion
      (cervical: 2.9% vs 1.0%, p<0.001; and lumbar: 21.0% vs 15.7%, p<0.001) and
      increased operative time (cervical: 167 vs 128 minutes, p<0.001; and lumbar: 226
      vs 204 minutes, p<0.001) relative to allograft. On multivariable analysis in both
      the cervical and lumbar cohorts, autograft was associated with increased odds of
      blood transfusion (cervical: OR 2.3, 95% CI 1.0-5.1; and lumbar: OR 1.3, 95% CI
      1.1-1.6) and longer operative times (cervical: 27.8 minutes, 95% CI 20.7-35.0;
      and lumbar: 25.4 minutes, 95% CI 17.7-33.1) relative to allograft. Autograft was
      not associated with either length of stay or SSI. CONCLUSIONS: In a multicenter
      cohort of patients undergoing cervical or lumbar spinal fusion, autograft was
      associated with increased rates of blood transfusion and increased operative time
      relative to allograft.

PMID- 27879953
TI  - Elective laminectomy and excision of the thoracic spine neoplasm: an evaluation
      of early outcomes.
AB  - BACKGROUND: Laminectomy plus excision of spinal neoplasms is commonly performed.
      The current study examines risk profiles associated with elective laminectomies
      of benign, malignant primary, and secondary/metastatic neoplasms of the thoracic
      spine. METHODS: Adult patients undergoing elective thoracic laminectomy and
      excision of spinal neoplasm were abstracted from ACS-NSQIP years 2011-2014.
      Patients were classified into three cohorts: benign primary, malignant primary,
      secondary/metastatic. Univariate and multivariable analyses compared operation
      time, early complications, hospital length of stay (HLOS), and discharge
      destination across cohorts. RESULTS: One-hundred sixty patients were included,
      aged 58.0+/-14.8-years. Mean operation time was 209.23+/-101.52 minutes and
      cohorts did not differ significantly on multivariable analysis. Mean HLOS was
      6.10+/-7.14 days and did not differ by cohort. Early complications were observed
      in 15.6% of patients; secondary/metastatic patients associated with increased
      odds of >1 unit of blood transfusion, but not overall complications. Failure to
      be discharged home occurred in 31.8% of patients (benign primary: 30.0%,
      malignant primary: 66.6%, secondary/metastatic: 10.5%; p<0.001). Malignant
      primary tumors associated with increased multivariable odds of failure to be
      discharged home (OR 3.63, 95% CI [1.09, 12.10], p=0.036). Tumor location
      (extradural, intradural/extramedullary, intramedullary) was not a significant
      predictor of outcomes. A higher number of concurrent fusions were observed for
      secondary/metastatic laminectomies (benign primary: 7.3%; malignant primary:
      5.5%; secondary/metastatic: 36.8%; p<0.001). CONCLUSIONS: Comparable performance
      on operation time and HLOS between neoplasm cohorts suggests broad indication of
      resectional laminectomies for elective treatment. Primary malignant thoracic
      spine tumors may require higher levels of early post-discharge care. Future
      studies are needed to confirm these findings.

PMID- 27879955
TI  - Hypobaric versus isobaric spinal levobupivacaine for total hip arthroplasty.
AB  - BACKGROUND: Spinal anesthesia (SA) in the lateral decubitus position is often
      used to perform total hip arthroplasty (THA). Hypobaric local anesthetic ensures
      enhanced and prolonged sensory and motor block in the involved side. The aim of
      this study was to compare the intraoperative anesthetic efficacy of hypobaric
      with isobaric levobupivacaine solutions for THA. METHODS: Forty patients
      scheduled to elective THA were allocated into two groups: isobaric
      levobupivacaine group (IL group) and hypobaric levobupivacaine group (HL group).
      All the patients were placed with the operative side uppermost on the surgical
      table and spinal anesthesia was performed with 4 mL (12.5 mg) of selected
      solution. The evolution of sensory and block on nondependent (operative) and
      dependent sides were checked. RESULTS: Regarding the nondependent side the onset
      times for maximal sensory block level in the in HL group was 17.8+/-1.1 minutes
      vs. 24.2+/-4.1 minutes in IL group. In HL group the onset time for motor block
      was 9.2+/-3.5 minutes vs. 15.6+/-5.4 minutes in IL group. The sensory regression
      time to L2 was significantly prolonged in HL group (192+/-30.3 minutes vs. 111+/
      13.4 min). After surgery in HL group the residual motor block degree was 2.4+/
      0.9 vs. 0.2+/-0.4 in IL group. CONCLUSIONS: In patients undergoing THA under
      spinal anesthesia 12.5 mg of hypobaric levobupivacaine, compared with the same
      dose of isobaric levobupivacaine, allow shorter onset time for sensory block and
      delayed regression of sensory and motor block in the nondependent side.

PMID- 27879954
TI  - Comparison of terminal extubation and terminal weaning as mechanical ventilation
      withdrawal in ICU patients.
AB  - BACKGROUND: Terminal extubation (TE) is applied in some Intensive Care Units
      (ICU) patients when a decision of withdrawal of mechanical ventilation is
      decided. Other units prefer terminal weaning (TW) with no removal of the
      endotracheal tube. We report our experience with these two procedures. METHODS:
      We conducted a retrospective study analyzing patients deceased in our ICU after a
      decision of life sustained therapy (LST) during the year 2013. TE was proposed to
      family members for patients presenting with two medical conditions: lack of
      vasoactive drugs (VAD) and SaO2>95% with a FIO2<50%. TW, defined by the reduction
      of oxygenation and/or the discontinuation of VAD, was proposed for patients
      receiving a FIO2>=50% and/or VAD. The two procedures were performed after
      obtaining a Cambridge Score-5 with sedatives. RESULTS: Sixty eight patients died
      after withdrawal of LST. TE was performed for 22 patients and TW for 46. There
      was no difference in mean age, mean length of ICU stay, cause of ICU admission
      and dose of sedatives used during withdrawal procedure between the two groups.
      All family members approved the decision of TE. In this group, family members of
      each patient were present in ICU room at time of death, while they were present
      at this moment for 32 (69.5%) patients with TW. CONCLUSIONS: In our Unit, TE is a
      practice largely approved by family members. This procedure does not require
      higher doses of sedatives and allows the nearest relatives to be present at time
      of death.

PMID- 27879956
TI  - Early tracheostomy in a case of toxic epidermal necrolysis with airways
      involvement.

PMID- 27879957
TI  - Use of the Sufentanil Sublingual Tablet System for postoperative pain relief in a
      patient with chronic liver disease.

PMID- 27879958
TI  - Six-year multicenter experience of standard endovascular treatment of critical
      limb ischemia in the era of drug-eluting devices.
AB  - BACKGROUND: There has been increasing evidence to support the endovascular-first
      approach in the treatment of below-the-knee (BTK) lesions. Plain old balloon
      angioplasty (POBA), with bailout bare-metal stent scaffolding in case of flow
      limiting dissection or recoil, have been considered the standard treatment of
      choice but industries are continually developing innovative equipment and
      dedicated technologies, such as drug-eluting platforms whose use is increasingly
      extended, despite significant costs and lack of high-quality evidence to support
      a well-established strategy. This study's objective was to analyze the 6-year
      results of "standard" endovascular treatment of BTK lesions in the era of drug
      eluting devices. METHODS: From August 2008 to February 2010, 21 French speaking
      European centers consecutively enrolled critical limb ischemia (CLI) patients
      with BTK lesions treated endovascularly into the Angioplastie Jambiere (ANJE)
      registry. Primary endpoint was 1-year limb salvage, a subgroup analysis was
      performed to compare POBA, bare nitinol stents and balloon-expandable stents
      (BESs). RESULTS: Of the 282 patients included (61.7%, men, mean age 75.8+/-10.0
      years), 53.5% were diabetic and 29.4% presented with chronic kidney disease. At 1
      year, complete wound healing was described in 187 patients (82.7%), the overall
      limb salvage rate was 94.0% with a survival rates of 89.2%. The primary and
      secondary patency rates were 84.5% and 91.7% respectively with significantly
      lower primary patency rates after stenting (80.6% vs. 87.6% after POBA; P=0.043).
      The rate of freedom from target lesion revascularization (TLR) was 86.3% with
      significantly lower rates after stenting (81.8% vs. 89.9% after POBA; P=0.01).
      The subgroup analysis showed no significant difference between nitinol stents,
      BESs and POBA in terms of limb salvage and survival rates, however, primary and
      secondary patency rates were significantly lower after BESs (primary and
      secondary patency rates of 84.0% after nitinol stents vs. 77.4% after BES vs.
      87.6% after POBA; P=0.012 and 93.0% vs. 77.4% vs. 87.6%; P=0.003, respectively),
      as well as freedom from TLR rates (82.3% vs. 81.2% vs. 89.9%; P=0.04).
      CONCLUSIONS: In the drug eluting era, the endovascular first approach of BTK
      lesions based on POBA with bailout spot stenting is feasible, affordable but most
      importantly remains effective and should be the first line strategy until the
      place of drug eluting stents is precisely defined.

PMID- 27879959
TI  - Balance versus resistance training on postural control in patients with
      Parkinson's disease: a randomized controlled trial.
AB  - BACKGROUND: Evidences have shown that physiotherapy programs may improve the
      balance of individuals with Parkinson's disease (PD), although it is not clear
      which specific exercise program is better. AIM: The aim of this study was to
      compare the effectiveness of balance versus resistance training on postural
      control measures in PD patients. DESIGN: Randomized controlled trial. SETTING:
      The study was conducted in a physiotherapy outpatient clinic of a university
      hospital. POPULATION: A total of 40 PD participants were randomly divided into
      two groups: balance training (BT) and resistance training (RT). METHODS: The BT
      group focused on balance training, functional independence and gait while the RT
      group performed resistance exercises emphasizing the lower limbs and trunk, both
      supervised by trained physiotherapists. Therapy sessions were held twice a week
      (at 60 minutes), totaling 24 sessions. The primary outcome was evaluated by force
      platform with center of pressure sway measures in different balance conditions
      and the secondary outcome was evaluated by Balance Evaluation Systems Test
      (BESTest) scale to determine the effects of the intervention on postural control.
      RESULTS: Significant improvement of postural control (pre vs. post 15.1 vs. 9.6
      cm2) was only reported in favor of BT group (d=1.17) for one-legged stand
      condition on force platform. The standardized mean difference between groups was
      significantly (P<0.02), with 36% of improvement for BT vs. 0.07% for RT on this
      condition. Significant improvement (P<0.05) was also observed in favor of BT (in
      mean 3.2%) for balance gains in some BESTest scores, when compared to RT group (
      0.98%). CONCLUSIONS: Postural control in Parkinson's disease is improved when
      training by a directional and specific balance program than a resistance training
      program. CLINICAL REHABILITATION IMPACT: Balance training is superior to
      resistance training in regard to improving postural control of individuals with
      PD. Gold standard instruments (high in cost and difficult to access) were used to
      assess balance, as well as scales with clinical applicability (low cost, easily
      acceptable, applicable and valid), which can guide the management of
      physiotherapists both in their decision-making and in clinical practice.

PMID- 27879960
TI  - Effectiveness of music-based interventions on motricity or cognitive functioning
      in neurological populations: a systematic review.
AB  - BACKGROUND: Motor and cognitive symptoms are frequent in persons with
      neurological disorders and often require extensive long-term rehabilitation.
      Recently, a variety of music-based interventions have been introduced into
      neurological rehabilitation as training tools. EVIDENCE ACQUISITION: This review
      aims to 1) describe and define music-based intervention modalities and content
      which are applied in experimental studies; and 2) describe the effects of these
      interventions on motor and/or cognitive symptoms in the neurological population.
      The databases PubMed and Web of Science were searched. Cited references of
      included articles where screened for potential inclusion. A systematic literature
      search up to 20th of June 2016 was conducted to include controlled trials and
      cohort studies that have used music-based interventions for >=3 weeks in the
      neurological population (in- and outpatients) targeting motor and/or cognitive
      symptoms. No limitations to publication date was set. EVIDENCE SYNTHESIS?
      Nineteen articles comprising thirteen randomized controlled trials (total
      participants Nexp=241, Nctrl=269), four controlled trials (Nexp=59, Nctrl=53) and
      two cohort studies (N.=27) were included. Fourteen studies were conducted in
      stroke, three in Parkinson's disease, and two in multiple sclerosis population.
      Modalities of music-based interventions were clustered into four groups:
      instrument-based, listening-based, rhythm-based, and multicomponent-based music
      interventions. Overall, studies consistently showed that music-based
      interventions had similar or larger effects than conventional rehabilitation on
      upper limb function (N.=16; fine motricity, hand and arm capacity, finger and
      hand tapping velocity/variability), mobility (N.=7; gait parameters), and
      cognition (N.=4; verbal memory and focused attention). CONCLUSIONS? Variety of
      modalities using music-based interventions has been identified and grouped into
      four clusters. Effects of interventions demonstrate an improvement in the domains
      assessed. Evidence is most available for improving motricity in stroke. More
      studies are warranted to investigate cognition as well as motor and cognition
      dysfunctions in combination. Instrument-based music interventions can improve
      fine motor dexterity and gross motor functions in stroke. Rhythm-based music
      interventions can improve gait parameters of velocity and cadence in stroke,
      Parkinson's disease and multiple sclerosis. Cognition in the domains of verbal
      memory and focused attention can improve after listening-based music
      interventions in stroke.

PMID- 27879961
TI  - Current aspects of pulmonary arterial hypertension and therapeutics.
AB  - The pulmonary arterial hypertension (PAH) patients have high rate of mortality
      due to right ventricle (or ventricular) (RV) failures. A lot of research work is
      being carried out in the area, however no treatment is available that could
      contrast the rise in mortality rates in PAH patients. beta1-adrenoceptor blockers
      (beta-blockers, BB) reduced mortality in left heart failure, but they do not
      explored much at clinical level. Recent studies suggest beta-blockers might be
      beneficial in PAH; however the mechanisms remain unknown. The present review
      article would put light on all these aspects of PAH along with latest ways for
      the management of PAH.

PMID- 27879962
TI  - Intestinal hormones, gut microbiota and non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the
      metabolic syndrome and has a complex pathophysiology with multiple pathways of
      development and progression implicated. Intestinal hormones regulate multiple
      biological functions and may play a role in the pathogenesis of non alcoholic
      fatty liver disease (NAFLD) by affecting food intake, body weight and insulin
      resistance. Bacterial products can affect the secretion of these hormones and
      thus have an effect on metabolism. Gut microbiota are normally involved in the
      intestinal energy harvest and their role has been increasingly been implicated in
      the pathogenesis of obesity and NAFLD. The intestinal hormone pathways as well as
      the intestinal microbiota populations are potential therapeutic targets in the
      management of NAFLD. We review the evidence on the associations of the intestinal
      hormones and gut microbiota in the development, progression and treatment of
      NAFLD.

PMID- 27879963
TI  - Hypogonadism and non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is more common in men than in women.
      Thus, it has been suggested that sex steroids do have a role in the development
      of NAFLD. The aim of the current paper is to illustrate the association between
      NAFLD and hypogonadism, by reviewing data derived from both human and animal
      studies. The prevalence of NAFLD is high in men with hypogonadism, including
      those with idiopathic hypogonadotropic hypogonadism (IHH), as well as in women in
      post-menopause, those under estrogen receptor antagonist treatment or women with
      Turner syndrome. Estrogens seem to play a pivotal role in hepatic lipid
      homeostasis, as demonstrated in animal models with diminished ovarian estrogens
      (i.e., ovariectomized mice) and low serum testosterone (T) concentration is
      independently associated with NAFLD. The elucidation of the exact role of sex
      steroids in NAFLD pathogenesis would create a unique opportunity to develop novel
      therapies to tackle NAFLD disease.

PMID- 27879964
TI  - Decreased levels of miR-34a and miR-217 act as predictor biomarkers of aggressive
      progression and poor prognosis in hepatocellular carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs) play key roles in tumor development and
      progression. The aim of this study was to explore the expression levels of miR
      34a and miR-217 in hepatocellular carcinoma (HCC) and to further investigate the
      clinicopathological and prognostic value of miR-34a and miR-217. METHODS: The
      expression levels of miR-34a and miR-217 were evaluated using quantitative real
      time PCR (qRT-PCR). Associations between these miRNAs expression and
      clinicopathological features were analyzed. Survival rate was determined with
      Kaplan-Meier and statistically analyzed with the log-rank method between groups.
      RESULTS: We found that miR-34a expression was significantly downregulated in HCC
      tissues (P<0.05). Reduced expression of miR-34a was associated with vascular
      invasion, and advanced TNM stage (P<0.05). Kaplan-Meier revealed that reduced
      expression of miR-34a was associated with poor overall survival (log-rank test,
      P<0.05). We found that miR-217 was downregulated in HCC tissues. Decreased
      expression of miR-217 was remarkably correlated vascular invasion, and advanced
      TNM stage (P<0.05). Kaplan-Meier analysis and log-rank test showed that HCC
      patients with low expression of miR-217 was associated with shorter overall
      survival than patients with high expression (log-rank test, P<0.05). CONCLUSIONS:
      Our data showed that downregulation of miR-34a and miR-217 was associated with
      HCC progression and both of them may act as tumor suppressor in HCC.

PMID- 27879965
TI  - Therapeutic approach to pediatric oral disorders.
AB  - The promotion of oral health in pediatrics stands as an institutional requirement
      in countries such as Italy where children's dental disorders still register a
      high incidence despite high levels of general health. Guidelines indicate the
      need to target a large age group and stress the relevance of parental education,
      whom pediatricians and dentists should address to. In this respect, teething is
      paradigmatic, due to the interactions between inflammation of the gingival
      mucosa, the possible associations with systemic symptoms as well as the
      psychological parental component. Teething products include: remedies used in
      folk medicine (chamomile and rose honey), whose clinical efficacy has not been
      proved; local anesthetics (lidocaine and benzocaine), easily absorbed by the oral
      mucosa and able to provide for a rapid, though short-lived relief; salicylates,
      prescribed by pediatricians in selected cases where the pain and inflammatory
      component is very high; systemic anti-inflammatory (paracetamol in elixir
      formulation), prescribed only in particularly serious cases, whereas they are
      sold over the counter in numerous countries; and - last but not least - film
      forming devices containing hyaluronic acid, whose efficacy has been clinically
      tested in various children disorders of the oral cavity, including teething.

PMID- 27879966
TI  - Andrological complications following retroperitoneal lymph node dissection for
      testicular cancer.
AB  - Retroperitoneal lymph node dissection (RPLND) is a fundamental surgical step in
      the treatment of testicular cancer. Nowadays, primary RPLND has partially lost
      its role in favour of active surveillance (for low risk stage I disease) and
      short cycle chemotherapy in non-seminomatous germ cell tumor (NSGCT). Conversely,
      post-chemotherapy RPLND (PC-RPLND) remains the standard treatment for residual
      masses after chemotherapy. In consideration of curability rate of testicular
      cancer and the life expectancy of testicular cancer survivors the identification
      and the prevention of andrological complications became fundamental. Erectile
      dysfunction (ED) is generally transitory and interests about 25% of patients,
      conversely retrograde ejaculation (RE) is definitive. Antegrade ejaculation is
      guaranteed by the sparing of at least one paravertebral sympathetic trunks and
      the postganglionic sympathetic fibers, which travel dorsal to the inferior vena
      cava and cross ventrally to the aorta. The maintenance of antegrade ejaculation
      can be obtained by a bilateral sparing of these fibers or by the modification of
      templates. In primary RPLND setting RE ranged between 2-6.7% and 1.2-61% in the
      major open and laparoscopic series respectively. In PC-RPLND series it ranged
      between 21-36% and 4-7.1% for open and laparoscopic approach respectively with
      the limitation of the restrictive indications of laparoscopic approach. The
      setting of this surgery and the importance of the oncological and functional
      outcomes that are pursued reinforced following the evidence that RPLND is a
      highly technical demanding procedure, whose best performances are achieved only
      when delivered in referral, high-volume centers.

PMID- 27879967
TI  - The influence of the medical treatment of LUTS on benign prostatic hyperplasia
      surgery: do we operate too late?
AB  - INTRODUCTION: The aim of this article is to systematically collect the available
      evidence on the influence of lower urinary tract symptoms (LUTS) medical
      treatment on benign prostatic hyperplasia (BPH) surgery. EVIDENCE ACQUISITION: A
      systematic literature search January 1990 until June 2016 was performed by
      combining the following MeSH terms: "lower urinary tract symptoms", "benign
      prostatic hyperplasia", "male", "medical treatment", "surgical treatment",
      "deferred/postponed treatment/intervention", "early intervention/treatment". Each
      article title and abstract was reviewed for relevance and appropriateness with
      regards to the topic of this review. EVIDENCE SYNTHESIS: The pharmacological
      treatment of LUTS is undoubtedly a successful story in the field of urology. Over
      the last two decades, the introduction of novel pharmaceutical agents has
      dramatically reduced the rate of BPH surgery interventions all over the world.
      Thus, nowadays, patients who undergo surgery are generally older, with more
      severe comorbidities and with larger prostates, theoretically requiring more
      challenging interventions. Nevertheless, the recent advances in surgical
      techniques and instruments have counterbalanced this unfavorable scenario and,
      overall, a non-pejorative trend has been observed in peri-/postoperative
      complications. On the other hand, evidence from the "pre-pharmacological
      treatment era" suggested that immediate BPH surgery might be the best option for
      patients at risk of severe BPH progression. Still, no clear-cut, shared criteria
      have yet been established to effectively identify these patients. CONCLUSIONS:
      Several questions remain unanswered regarding the role of medical treatment in
      BPH, and good-quality studies available on this topic are surprisingly rare. The
      evidence presented in this review supports the need for prospective comparative
      studies evaluating long-term LUTS/BPH pharmacological treatment versus an early
      surgical intervention, particularly using the emerging laser technologies.

PMID- 27879968
TI  - Can urinary indolylacroylglycine levels be used to determine whether children
      with autism will benefit from dietary intervention?
AB  - BACKGROUND: An increase in urinary indolyl-3-acryloylglycine (IAG) has been
      reported in children with autism spectrum disorders (ASD) who suffer with bowel
      problems in comparison to ASD children without gastrointestinal (GI) problems.
      The case for dietary intervention for ASD children with GI symptoms might be
      strengthened were such a difference to be autism-specific. METHODS: Quantitative
      analysis of urinary IAG levels was performed for 53 children on the autism
      spectrum and 146 age-matched controls. The parents of each child were asked to
      provide information on bowel symptoms experienced by the child and their eating
      habits over a period of 2 wk. RESULTS: We find no significant difference in
      urinary IAG levels between the ASD children with GI problems and ASD children
      without GI problems. Although we see some difference between ASD children with GI
      problems and controls in mainstream schools with GI problems, the difference
      between non-autistic children with other developmental disorders and controls in
      mainstream schools is more significant so that any difference is not autism
      specific. We find a strong correlation between bowel symptoms and diet problems
      in ASD children, especially idiosyncratic feeding behavior and we show that ASD
      children suffering from multiple bowel symptoms tend to be those who also have
      dietary problems. CONCLUSION: We found no evidence to support the hypothesis that
      children with ASD who suffer with bowel problems have increased levels of urinary
      IAG in comparison to children with ASD who do not have gastrointestinal problems.

PMID- 27879970
TI  - Mortality, hospital days and expenditures attributable to ambient air pollution
      from particulate matter in Israel.
AB  - BACKGROUND: Worldwide, ambient air pollution accounts for around 3.7 million
      deaths annually. Measuring the burden of disease is important not just for
      advocacy but also is a first step towards carrying out a full cost-utility
      analysis in order to prioritise technological interventions that are available to
      reduce air pollution (and subsequent morbidity and mortality) from industrial,
      power generating and vehicular sources. METHODS: We calculated the average
      national exposure to particulate matter particles less than 2.5 MUm (PM2.5) in
      diameter by weighting readings from 52 (non-roadside) monitoring stations by the
      population of the catchment area around the station. The PM2.5 exposure level was
      then multiplied by the gender and cause specific (Acute Lower Respiratory
      Infections, Asthma, Circulatory Diseases, Coronary Heart Failure, Chronic
      Obstructive Pulmonary Disease, Diabetes, Ischemic Heart Disease, Lung Cancer, Low
      Birth Weight, Respiratory Diseases and Stroke) relative risks and the national
      age, cause and gender specific mortality (and hospital utilisation which included
      neuro-degenerative disorders) rates to arrive at the estimated mortality and
      hospital days attributable to ambient PM2.5 pollution in Israel in 2015. We
      utilised a WHO spread-sheet model, which was expanded to include relative risks
      (based on more recent meta-analyses) of sub-sets of other diagnoses in two
      additional models. RESULTS: Mortality estimates from the three models were 1609,
      1908 and 2253 respectively in addition to 184,000, 348,000 and 542,000 days
      hospitalisation in general hospitals. Total costs from PM2.5 pollution (including
      premature burial costs) amounted to $544 million, $1030 million and $1749 million
      respectively (or 0.18 %, 0.35 % and 0.59 % of GNP). CONCLUSIONS: Subject to the
      caveat that our estimates were based on a limited number of non-randomly sited
      stations exposure data. The mortality, morbidity and monetary burden of disease
      attributable to air pollution from particulate matter in Israel is of sufficient
      magnitude to warrant the consideration of and prioritisation of technological
      interventions that are available to reduce air pollution from industrial, power
      generating and vehicular sources. The accuracy of our burden estimates would be
      improved if more precise estimates of population exposure were to become
      available in the future.

PMID- 27879971
TI  - TCR diversity - a universal cancer immunotherapy biomarker?
AB  - Sipuleucel-T was approved as a treatment for men with advanced metastatic,
      castration-resistant prostate cancer on the basis of improved survival in
      randomized clinical trials. A major challenge for this therapy, as well as other
      newer cancer immunotherapy agents, has been to identify markers that can identify
      patients who benefit from these therapies. In a recent manuscript by Sheikh and
      colleagues, the investigators evaluated changes in T cell clonality in the
      peripheral blood and tumors of patients treated with sipuleucel-T using next
      generation sequencing of T cell receptor Vbeta CDR3 sequences. Their findings are
      discussed in the context of this trial and other cancer immunotherapies.

PMID- 27879969
TI  - Factors associated with choice of approach for Group B streptococcus screening.
AB  - BACKGROUND: The crude rate of early-onset Group B streptococcus disease (EOGBS)
      in Israel has been consistently under 0.5 for 1000 live births for the past 8
      years. The Israeli Ministry of Health has adapted the risk factor based approach
      for preventing EOGBS and universal bacteriological screening for GBS is not
      recommended. In spite of this policy, there are indications that many pregnant
      women in Israel undergo bacteriological screening for GBS. The objective of this
      study is to assess the rate and characteristics of pregnant women who undergo
      screening for group B streptococcus (GBS) colonization in Israel. METHODS: Survey
      of expectant mothers who came to give birth in 29 delivery rooms throughout
      Israel during the month of July 2012 regarding GBS screening practice and
      demographics. RESULTS: A total of 2968 pregnant women participated in the
      assessment. Among them, 935 women (31.5 %) had been tested for GBS colonization.
      About 90 % of those women had no risk factors, only 542 women (60 %) underwent
      testing during the recommended gestational timing (35-37 weeks) and 23 % of the
      tested women reported being GBS carriers. GBS screening as part of the routine
      pregnancy follow- up was associated with: residence district, intermediate or
      high socioeconomic rank, being a member of certain health maintenance
      organization and being Jewish. Characteristics found to be significantly
      associated with being a GBS carrier were: low socioeconomic rank, and having a
      risk factor for GBS infection. CONCLUSIONS: A substantial number of pregnant
      women in Israel undergo screening for GBS colonization despite the national
      policy against universal screening. While GBS colonization was more prevalent in
      women of lower socioeconomic status, screening is done more often in those of
      higher socioeconomic status, suggesting unnecessary monetary expenses.

PMID- 27879972
TI  - Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti
      PD1 monoclonal antibody REGN2810.
AB  - BACKGROUND: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma
      (CSCC) share exposure to UV light as the dominant risk factor, and these tumors
      therefore harbor high mutation burdens. In other malignancies, high mutation
      burden has been associated with clinical benefit from therapy with antibodies
      directed against the Programmed Death 1 (PD-1) immune checkpoint receptor. Highly
      mutated tumors are more likely to express immunogenic tumor neoantigens that
      attract effector T cells, which can be unleashed by blockade of the PD-1 immune
      checkpoint. CASE PRESENTATIONS: This report describes a patient with metastatic
      BCC and a patient with metastatic CSCC who were treated with REGN2810, a fully
      human anti-PD-1 monoclonal antibody, in an ongoing phase 1 trial (NCT02383212).
      The CSCC patient has experienced an ongoing complete response (16+ months), and
      the BCC patient has experienced an ongoing partial response (12+ months).
      CONCLUSIONS: These case reports suggest that UV-associated skin cancers, beyond
      melanoma, are sensitive to PD-1 blockade. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT02383212. Registered 2 February 2015.

PMID- 27879973
TI  - Application of the Immunoscore as prognostic tool for hepatocellular carcinoma.
AB  - To date, the American Joint Committee on Cancer (AJCC) and the Union for
      International Cancer Control (UICC) tumor, nodes, metastasis (TNM) classification
      represents the standard system for evaluation of prognosis in solid tumors.
      However, the clinical outcome can be significantly different in patients with the
      same TNM stage. Therefore, many efforts have been made aiming to define new
      prognostic parameters. Indeed, analyses conducted in large cohorts of colorectal
      cancer patients emphasized the prognostic value of tumor-infiltrating
      lymphocytes, leading to the development of a prognostic score referred to as
      "Immunoscore". In this commentary, we recapitulate the study by Gabrielson and
      colleagues, recently published in Cancer Immunology Research, addressing the role
      of intratumoral CD3+ and CD8+ T cells as well as as prognostic markers for
      hepatocellular carcinoma. The authors demonstrate that Immunoscore represents a
      valuable prognostic marker in patients with hepatocellular carcinoma who have
      undergone primary tumor resection, supporting its application in a tumor setting
      other than colorectal cancer.

PMID- 27879974
TI  - Nivolumab dose selection: challenges, opportunities, and lessons learned for
      cancer immunotherapy.
AB  - BACKGROUND: Immuno-oncology (I-O) therapies target the host immune system,
      providing the potential to choose a uniform dose and schedule across tumor types.
      However, dose selection for I-O agents usually occurs early in clinical
      development and is typically based on tumor response, which may not fully
      represent the potential for improved overall survival. Here, we describe an
      integrated approach which incorporates clinical safety and efficacy data with
      data obtained from analyses of dose-/exposure-response (D-R/E-R) relationships,
      used to select a monotherapy dose for nivolumab, a programmed death-1 inhibitor,
      in clinical studies of different tumor types. METHODS: Dose was selected based on
      anti-tumor activity and safety data from a large phase 1b, open-label, dose
      escalation study of nivolumab at doses ranging from 0.1 to 10 mg/kg administered
      every 2 weeks (Q2W) in 306 patients with advanced malignancies, and quantitative
      analyses were performed to characterize D-R/E-R relationships for
      pharmacodynamic, safety, and efficacy endpoints. RESULTS: A maximum tolerated
      dose for nivolumab was not identified, and the safety profile was similar across
      tumor types and dose levels (0.1-10 mg/kg). Objective response rates (ORRs) were
      similar across doses in melanoma and renal cell carcinoma (RCC), while higher
      ORRs were observed in non-small cell lung cancer (NSCLC) at 3 mg/kg and 10 mg/kg
      versus 1 mg/kg. Peripheral receptor occupancy was saturated at doses >= 0.3
      mg/kg. In D-R/E-R analyses, a positive dose-dependent objective response trend
      was observed for each tumor type, but appeared to plateau at nivolumab doses of
      >= 1 mg/kg for melanoma and RCC, and at >= 3 mg/kg for NSCLC. Although there was
      no apparent relationship between tumor shrinkage rate and exposure, tumor
      progression rate appeared to decrease with increasing exposure up to a dose of 3
      mg/kg Q2W for NSCLC. CONCLUSIONS: Nivolumab monotherapy at 3 mg/kg Q2W provides
      unified dosing across tumor types. This dose and schedule has been validated in
      several phase II/III studies in which overall survival was an endpoint.
      Integrating D-R/E-R relationships with efficacy data and a safety profile that is
      unique to I-O therapy is a rational approach for dose selection of these agents.

PMID- 27879975
TI  - Metastatic Merkel cell carcinoma response to nivolumab.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine
      malignancy with limited treatment options. Several lines of evidence support the
      programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis as a likely
      contributor to immune evasion in MCC. CASE PRESENTATION: We report a case of a
      patient with metastatic MCC with a significant and durable response to nivolumab,
      a humanized IgG4 monoclonal anti-PD-1 antibody. CONCLUSION: Immunotherapy with PD
      1/PD-L1 inhibitors has become a rational and promising treatment option for MCC
      in the advanced or metastatic disease. Clinical trials are currently in progress
      to further evaluate these novel therapeutic agents.

PMID- 27879976
TI  - Correction: Downsizing the BAD BH3 peptide to small constrained alpha-helices
      with improved ligand efficiency.
AB  - Correction for 'Downsizing the BAD BH3 peptide to small constrained alpha-helices
      with improved ligand efficiency' by Nicholas E. Shepherd et al., Org. Biomol.
      Chem., 2016, DOI: 10.1039/c6ob02185a.

PMID- 27879980
TI  - Theory-based interventions for contraception.
AB  - BACKGROUND: The explicit use of theory in research helps expand the knowledge
      base. Theories and models have been used extensively in HIV-prevention research
      and in interventions for preventing sexually transmitted infections (STIs). The
      health behavior field uses many theories or models of change. However, many
      educational interventions addressing contraception have no explicit theoretical
      base. OBJECTIVES: To review randomized controlled trials (RCTs) that tested a
      theoretical approach to inform contraceptive choice and encourage or improve
      contraceptive use. SEARCH METHODS: To 1 November 2016, we searched for trials
      that tested a theory-based intervention for improving contraceptive use in
      PubMed, CENTRAL, POPLINE, Web of Science, ClinicalTrials.gov, and ICTRP. For the
      initial review, we wrote to investigators to find other trials. SELECTION
      CRITERIA: Included trials tested a theory-based intervention for improving
      contraceptive use. Interventions addressed the use of one or more methods for
      contraception. The reports provided evidence that the intervention was based on a
      specific theory or model. The primary outcomes were pregnancy and contraceptive
      choice or 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 unadjusted dichotomous outcomes, we calculated the
      Mantel-Haenszel odds ratio (OR) with 95% confidence interval (CI). Cluster
      randomized trials used various methods of accounting for the clustering, such as
      multilevel modeling. Most reports did not provide information to calculate the
      effective sample size. Therefore, we presented the results as reported by the
      investigators. We did not conduct meta-analysis due to varied interventions and
      outcome measures. MAIN RESULTS: We included 10 new trials for a total of 25. Five
      were conducted outside the USA. Fifteen randomly assigned individuals and 10
      randomized clusters. This section focuses on nine trials with high or moderate
      quality evidence and an intervention effect. Five based on social cognitive
      theory addressed preventing adolescent pregnancy and were one to two years long.
      The comparison was usual care or education. Adolescent mothers with a home-based
      curriculum had fewer second births in two years (OR 0.41, 95% CI 0.17 to 1.00).
      Twelve months after a school-based curriculum, the intervention group was more
      likely to report using an effective contraceptive method (adjusted OR 1.76 +/-
      standard error (SE) 0.29) and using condoms during last intercourse (adjusted OR
      1.68 +/- SE 0.25). In alternative schools, after five months the intervention
      group reported more condom use during last intercourse (reported adjusted OR
      2.12, 95% CI 1.24 to 3.56). After a school-based risk-reduction program, at three
      months the intervention group was less likely to report no condom use at last
      intercourse (adjusted OR 0.67, 95% CI 0.47 to 0.96). The risk avoidance group
      (abstinence-focused) was less likely to do so at 15 months (OR 0.61, 95% CI 0.45
      to 0.85). At 24 months after a case management and peer-leadership program, the
      intervention group reported more consistent use of hormonal contraceptives
      (adjusted relative risk (RR) 1.30, 95% CI 1.06 to 1.58), condoms (RR 1.57, 95% CI
      1.28 to 1.94), and dual methods (RR 1.36, 95% CI 1.01 to 1.85).Four of the nine
      trials used motivational interviewing (MI). In three studies, the comparison
      group received handouts. The MI group more often reported effective contraception
      use at nine months (OR 2.04, 95% CI 1.47 to 2.83). In two studies, the MI group
      was less likely to report using ineffective contraception at three months (OR
      0.31, 95% CI 0.12 to 0.77) and four months (OR 0.56, 95% CI 0.31 to 0.98),
      respectively. In the fourth trial, the MI group was more likely than a group with
      non-standard counseling to initiate long-acting reversible contraception (LARC)
      by one month (OR 3.99, 95% CI 1.36 to 11.68) and to report using LARC at three
      months (OR 3.38, 95% CI 1.06 to 10.71). AUTHORS' CONCLUSIONS: The overall quality
      of evidence was moderate. Trials based on social cognitive theory focused on
      adolescents and provided multiple sessions. Those using motivational interviewing
      had a wider age range but specific populations. Sites with low resources need
      effective interventions adapted for their settings and their typical clients.
      Reports could be clearer about how the theory was used to design and implement
      the intervention.

PMID- 27879981
TI  - Zinc supplementation for tinnitus.
AB  - BACKGROUND: Tinnitus is the perception of sound without external acoustic
      stimuli. Patients with severe tinnitus may have physical and psychological
      complaints and their tinnitus can cause deterioration in their quality of life.
      At present no specific therapy for tinnitus has been found to be satisfactory in
      all patients. In recent decades, a number of reports have suggested that oral
      zinc supplementation may be effective in the management of tinnitus. Since zinc
      has a role in cochlear physiology and in the synapses of the auditory system,
      there is a plausible mechanism of action for this treatment. OBJECTIVES: To
      evaluate the effectiveness and safety of oral zinc supplementation in the
      management of patients with tinnitus. SEARCH METHODS: The Cochrane ENT
      Information Specialist searched the ENT Trials Register; Central Register of
      Controlled Trials (CENTRAL 2016, Issue 6); PubMed; EMBASE; CINAHL; Web of
      Science; ClinicalTrials.gov; ICTRP and additional sources for published and
      unpublished trials. The date of the search was 14 July 2016. SELECTION CRITERIA:
      Randomised controlled trials comparing zinc supplementation versus placebo in
      adults (18 years and over) with tinnitus. DATA COLLECTION AND ANALYSIS: We used
      the standard methodological procedures recommended by Cochrane. Our primary
      outcome measures were improvement in tinnitus severity and disability, measured
      by a validated tinnitus-specific questionnaire, and adverse effects. Secondary
      outcomes were quality of life, change in socioeconomic impact associated with
      work, change in anxiety and depression disorders, change in psychoacoustic
      parameters, change in tinnitus loudness, change in overall severity of tinnitus
      and change in thresholds on pure tone audiometry. We used GRADE to assess the
      quality of the evidence for each outcome; this is indicated in italics. MAIN
      RESULTS: We included three trials involving a total of 209 participants. The
      studies were at moderate to high risk of bias. All included studies had
      differences in participant selection criteria, length of follow-up and outcome
      measurement, precluding a meta-analysis. The participants were all adults over 18
      years with subjective tinnitus, but one study conducted in 2013 (n = 109)
      included only elderly patients. Improvement in tinnitus severity and
      disabilityOnly the study in elderly patients used a validated instrument
      (Tinnitus Handicap Questionnaire) for this primary outcome. The authors of this
      cross-over study did not report the results of the two phases separately and
      found no significant differences in the proportion of patients reporting tinnitus
      improvement at four months of follow-up: 5% (5/93) versus 2% (2/94) in the zinc
      and placebo groups, respectively (risk ratio (RR) 2.53, 95% confidence interval
      (CI) 0.50 to 12.70; very low-quality evidence).None of the included studies
      reported any significant adverse effects. Secondary outcomesFor the secondary
      outcome change in tinnitus loudness, one study reported no significant difference
      between the zinc and placebo groups after eight weeks: mean difference in
      tinnitus loudness -9.71 dB (95% CI -25.53 to 6.11; very low-quality evidence).
      Another study also measured tinnitus loudness but used a 0- to 100-point scale.
      The authors of this second study reported no significant difference between the
      zinc and placebo groups after four months: mean difference in tinnitus loudness
      rating scores 0.50 (95% CI -5.08 to 6.08; very low-quality evidence).Two studies
      used unvalidated instruments to assess tinnitus severity. One (with 50
      participants) reported the severity of tinnitus using a non-validated scale (0 to
      7 points) and found no significant difference in subjective tinnitus scores
      between the zinc and placebo groups at the end of eight weeks of follow-up (mean
      difference (MD) -1.41, 95% CI -2.97 to 0.15; very low-quality evidence). A third
      trial (n = 50) also evaluated the improvement of tinnitus using a non-validated
      instrument (a 0 to 10 scale: 10 = severe and unbearable tinnitus). In this study,
      after eight weeks there was no difference in the proportion of patients with
      improvement in their tinnitus, 8.7% (2/23) treated with zinc versus 8% (2/25) of
      those who received a placebo (RR 1.09, 95% CI 0.17 to 7.10, very low-quality
      evidence).None of the included studies reported any of our other secondary
      outcomes (quality of life, change in socioeconomic impact associated with work,
      change in anxiety and depression disorders, change in psychoacoustic parameters
      or change in thresholds on pure tone audiometry). AUTHORS' CONCLUSIONS: We found
      no evidence that the use of oral zinc supplementation improves symptoms in adults
      with tinnitus.

PMID- 27879982
TI  - Resistance Band Exercises Reduce Depression and Behavioral Problems of Wheelchair
      Bound Older Adults with Dementia: A Cluster-Randomized Controlled Trial.
AB  - OBJECTIVES: To test the effects of a 15-month wheelchair-bound resistance band
      exercise program on depression and behavioral problems of wheelchair-bound older
      adults with dementia. DESIGN: Single-blind, cluster-randomized controlled trial
      with repeated measures. SETTING: Eight nursing homes in southern Taiwan.
      PARTICIPANTS: Wheelchair-bound nursing home older adults with dementia who
      participated voluntarily (N = 150) were cluster-randomized to two groups
      (experimental or control group); 127 completed the study (experimental: four
      nursing homes, n = 65; control: four nursing homes, n = 62). INTERVENTION: The
      resistance band exercises were conducted three times per week in 40-minute
      sessions in the following two sequences: volunteer-led sessions for the first 6
      months (Stage I) followed by DVD-guided sessions for the next 9 months (Stage
      II). MEASUREMENTS: Depression, as measured using the Cornell Scale for Depression
      in Dementia, and behavioral problems, as measured using the Clifton Assessment
      Procedures for the Elderly-Behavior Rating Scale, of participants were observed
      at six time points at 3-month intervals: pretest, two posttests at Stage I, and
      three posttests at Stage II. RESULTS: By the sixth month of the study,
      experimental group participants were significantly less depressed and had fewer
      behavioral problems than control group participants (all P < .05). These small
      but statistically significant differences persisted throughout the 9 months of
      the DVD-guided sessions (all P < .05). CONCLUSION: Volunteer-led sessions
      followed by DVD-guided sessions of resistance band exercise is effective and
      practical in institutional settings.

PMID- 27879983
TI  - Delirium: A Survey of Healthcare Professionals' Knowledge, Beliefs, and
      Practices.
AB  - OBJECTIVES: To evaluate knowledge, beliefs, and practices regarding delirium of
      physicians, nurse practitioners (NPs), and registered nurses (RNs). DESIGN:
      Anonymous cross-sectional paper survey. SETTING: New York metropolitan area
      tertiary care hospital. PARTICIPANTS: RNs, NPs, and physicians (N = 164).
      MEASUREMENTS: The survey assessed knowledge, beliefs, and practices regarding
      delirium and prior delirium or geriatric training. RESULTS: Of the 200 surveys
      distributed, 164 were completed (82% response rate). Of these, 61.7% were RNs,
      13.6% were NPs, and 20.7% were physicians. Mean participant age was 36.3. The
      majority (80.1%) were female; 56.5% were white, 18.1% Asian, 8.7% Hispanic, 8.0%
      black, and 8.7% other. Of the seven potential barriers to delirium screening
      assessed, the three most frequently reported were lack of conceptual
      understanding of delirium (48.0%), similarity of delirium and dementia (41.4%),
      and the fluctuating nature of delirium (38.1%). Physicians were more likely than
      NPs and RNs to report being confident in identifying delirium (P = .002) and to
      score higher on the delirium knowledge assessment (P < .001). Participants who
      received geriatrics training were significantly more likely than those who did
      not to be confident in identifying delirium (P = .005) and to score higher on
      overall delirium knowledge assessment (P = .003). CONCLUSION: Geriatric training
      is associated with more confidence in delirium screening and higher delirium
      knowledge scores. There is an urgent need to broaden the approach to delirium
      education of nurses and physicians caring for hospitalized older adults using
      comprehensive multidisciplinary geriatric educational models.

PMID- 27879985
TI  - Criterion Validity of a Frailty Index Derived from the Easycare Instrument.

PMID- 27879984
TI  - No End in Sight: Benzodiazepine Use in Older Adults in the United States.
AB  - OBJECTIVES: To establish the rate of new and continuation of benzodiazepine use
      in older adults seen by nonpsychiatrist physicians and to identify subpopulations
      at risk of new and continuation benzodiazepine use. DESIGN: Cross-sectional
      analysis. SETTING: National Ambulatory Medical Care Survey (2007-10).
      PARTICIPANTS: Adults visiting office-based nonpsychiatrist physicians (n =
      98,818) who were prescribed a benzodiazepine (new or continuation). MEASUREMENTS:
      Percentage of benzodiazepine visits of all outpatient encounters according to
      patient age and corresponding annual visit rate per 1,000 population. Analysis
      was then limited to adults aged 65 and older, demographic, clinical, and visits
      characteristics were used to compare visits of benzodiazepine users with those of
      nonusers and visits of continuation users with those of new users. RESULTS: The
      overall proportion of benzodiazepine visits ranged from 3.2% (95% confidence
      interval (CI) = 2.7-3.7) of those aged 18 to 34 to 6.6% (95% CI = 5.8-7.6) of
      those aged 80 and older, and the proportion of continuation visits increased with
      age, rising to 90.2% (95% CI = 86.2-93.1) of those aged 80 and older. The
      population-based visit rate ranged from 61.7 (95% CI = 50.7-72.7) per 1,000
      persons in the youngest adults to 463.7 (95% CI = 385.4-542.0) in those aged 80
      and older. Only 16.0% (95% CI = 13.5-18.8) of continuation users had any mental
      health diagnosis. Of all benzodiazepine users, fewer than 1% (95% CI = .4-1.8)
      were provided or referred to psychotherapy, and 10.0% (95% CI = 7. 2-13.3) were
      also prescribed an opioid. CONCLUSION: In the United States, few older adult
      benzodiazepine users receive a clinical mental health diagnosis, and almost none
      are provided or referred to psychotherapy. Prescribing to older adults continues
      despite decades of evidence documenting safety concerns, effective alternative
      treatments, and effective methods for tapering even chronic users.

PMID- 27879986
TI  - Anticholinergic Burden in Older Adults with Mild Cognitive Impairment.

PMID- 27879987
TI  - Ocular extramedullary myeloid leukaemia.

PMID- 27879988
TI  - Immune thrombocytopenia: a need for assisted suicide.

PMID- 27879989
TI  - CD274 (PD-L1)/PDCD1 (PD-1) expression in de novo and transformed diffuse large B
      cell lymphoma.

PMID- 27879990
TI  - Sequential chemotherapy followed by reduced-intensity conditioning and allogeneic
      haematopoietic stem cell transplantation in adult patients with relapse or
      refractory acute myeloid leukaemia: a survey from the Acute Leukaemia Working
      Party of EBMT.
AB  - This study analysed the outcome of 267 patients with relapse/refractory acute
      myeloid leukaemia (AML) who received sequential chemotherapy including
      fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning
      (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The
      transplants in 77 patients were from matched sibling donors (MSDs) and those in
      190 patients were from matched unrelated donors. Most patients (94.3%) were given
      anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD)
      of grades II-IV was 32.1% and that of chronic GVHD was 30.2%. The 3-year
      probability of non-relapse mortality (NRM) was 25.9%, that of relapse was 48.5%,
      that of GVHD-free and relapse-free survival (GRFS) was 17.8% and that of
      leukaemia-free survival (LFS) was 25.6%. In multivariate analysis, unrelated
      donor recipients more frequently had acute GVHD of grades II-IV [hazard ratio
      (HR) = 1.98, P = 0.017] and suffered less relapses (HR = 0.62, P = 0.01) than MSD
      recipients. Treatment with anti-T-cell antibodies reduced NRM (HR = 0.35, P =
      0.01) and improved survival (HR = 0.49, P = 0.01), GRFS (HR = 0.37, P = 0.0004)
      and LFS (HR = 0.46, P = 0.005). Thus, sequential chemotherapy followed by RIC
      HSCT and use of anti-T-cell antibodies seems promising in patients with
      refractory AML.

PMID- 27879991
TI  - Clients' Retrospective Accounts of Corrective Experiences in Psychotherapy: An
      International, Multisite Collaboration.
AB  - This article introduces a series of 4 original research reports that used varied
      qualitative methods for understanding an internationally diverse sample of
      clients' own accounts of corrective experiences (CEs), as they looked back on
      their completed psychotherapy. The basis for all studies, which were conducted
      across 4 different countries, was the Patients' Perceptions of Corrective
      Experiences in Individual Therapy (PPCEIT) semistructured interview protocol
      (Constantino, Angus, Friedlander, Messer, & Moertl, 2011). The PPCEIT interview
      assesses clients' retrospective accounts of aspects of self, other, and/or
      relationships that may have been corrected, and what they perceived as corrective
      experiences that facilitated such transformations. It also asks for specific,
      detailed examples of these accounts and experiences. Across all studies, the
      PPCEIT interview generated rich clinical material and resulting empirically
      generated themes that may inform clinical practice. After briefly defining the CE
      construct and highlighting a lack of research on clients' own accounts of such
      experiences, we describe the development of the PPCEIT interview (and provide the
      full interview manual and question protocol as appendices). We then summarize the
      foci of the culturally diverse reports in this series.

PMID- 27879992
TI  - Spleen hypofunction in eosinophilic gastrointestinal disease.

PMID- 27879993
TI  - Randomized clinical trial of preoperative skin antisepsis with chlorhexidine
      gluconate or povidone-iodine.
AB  - BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection
      (SSI); few trials have reported the superiority of any specific agent in clean
      contaminated abdominal surgery. This RCT was designed to compare the
      effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS:
      Consecutive patients who underwent clean-contaminated upper gastrointestinal or
      hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned
      randomly to either chlorhexidine gluconate or povidone-iodine. The primary
      endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints
      included causative organisms and risk factors for SSI. RESULTS: A total of 534
      patients were randomized; 31 (5.8 per cent) developed an SSI. There was no
      difference in the overall SSI rate in the chlorhexidine gluconate and povidone
      iodine groups: 15 of 267 (5.6 per cent) and 16 of 267 (6.0 per cent) respectively
      (P = 0.853). The most common causative organism was Enterococcus faecalis. In
      subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127,
      20.5 per cent) than upper gastrointestinal (2 of 204, 1.0 per cent) and hepatic
      (3 of 203, 1.5 per cent) resection. Both age (60 years and over) and type of
      incision were associated with the risk of SSI. CONCLUSION: No difference was
      detected between chlorhexidine gluconate and povidone-iodine antiseptics for
      prevention of SSI. Registration number: NCT01495117
      (http://www.clinicaltrials.gov).

PMID- 27879994
TI  - A new mutation of ANO6 in two familial cases of Scott syndrome.

PMID- 27879996
TI  - Microaggressions: An Approach to Understanding the Health of Workers in Long-Term
      Care Settings.

PMID- 27879995
TI  - EGFR gene copy number predicts response to anti-EGFR treatment in RAS wild type
      and RAS/BRAF/PIK3CA wild type metastatic colorectal cancer.
AB  - Anti-EGFR antibodies are used for the treatment of RAS wild type metastatic
      colorectal cancer. We previously showed that EGFR gene copy number (GCN) predicts
      response to anti-EGFR therapy in KRAS exon 2 wild type metastatic colorectal
      cancer. The aim of our study was to analyse the predictive role of EGFR GCN in
      RAS/BRAF/PIK3CA wild type metastatic colorectal cancer. The material included 102
      patients with KRAS exon 2 wild type metastatic colorectal cancer treated with
      anti-EGFR +/- cytotoxic therapy. Next generation sequencing was used for KRAS,
      NRAS, BRAF and PIK3CA gene mutation analyses. EGFR GCN was analysed by EGFR
      immunohistochemistry guided automated silver in situ hybridisation. Increased
      EGFR GCN (>=4.0) predicted a better response and prolonged progression free
      survival in anti-EGFR treated RAS/BRAF/PIK3CA wild type patients (Log-rank test,
      p = 0.0004). In contrast, survival of RAS/BRAF/PIK3CA wild type, EGFR GCN below
      4.0 patients did not differ from patients with mutant RAS, BRAF or PIK3CA. Our
      study indicates that EGFR GCN predicts anti-EGFR treatment efficacy in patients
      with RAS/BRAF/PIK3CA wt metastatic CRC. Tumours with EGFR GCN below 4.0 appear to
      be as refractory to anti-EGFR treatment as tumours with mutation in any of the
      RAS/RAF/PIK3CA pathway genes.

PMID- 27879998
TI  - Patients' Perceptions of Corrective Experiences in Naturalistically Delivered
      Psychotherapy.
AB  - Corrective experiences (CEs), which suggest transformative experience(s) for the
      psychotherapy patient, have a rich theoretical history; yet there is little
      empirical information on patients' own perceptions of what gets "corrected" from
      therapy, and what is "corrective" (i.e., the mechanisms driving the CE). To
      address this gap, we investigated 14 patients' posttreatment accounts of both CE
      elements in the context of naturalistically delivered individual psychotherapy,
      using a consensual qualitative research methodology. Extending prior research
      focused on patients' accounts of CEs while still engaged in treatment
      (Heatherington et al., 2012), the present results revealed that patients
      retrospectively identified an array of categories that were deemed corrected,
      such as positive changes in cognitions, interpersonal problems, self-concepts,
      symptoms, and behaviors. Patients also identified CEs that may have led to those
      shifts/transformations, including their therapist's actions (especially giving
      feedback), their own agentic actions (especially engaging in the therapeutic
      process), and the patient-therapist collaborative and engaged relationship.
      Clinical practice implications are discussed.

PMID- 27879997
TI  - A United Kingdom Immune Thrombocytopenia (ITP) Forum review of practice:
      thrombopoietin receptor agonists.

PMID- 27879999
TI  - Addendum to the British Committee for Standards in Haematology (BCSH): guidelines
      for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant, 2004
      (Br. J Haematol 2004,126,11-28) - response to Neisser-Svae and Heger.

PMID- 27880000
TI  - Reply to 'A phase II randomized controlled trial of nicotinamide for skin cancer
      chemoprevention in renal transplant recipients'.

PMID- 27880001
TI  - Oligomeric form of C-terminal-binding protein coactivates NeuroD1-mediated
      transcription.
AB  - The mechanism underlying transcriptional coactivation by the corepressor C
      terminal-binding protein (CtBP) is not established. We previously found that CtBP
      co-occupies several actively transcribed endocrine genes with the transcription
      factor NeuroD1 to paradoxically increase transcription by recruiting KDM1A and
      CoREST. While the importance of the oligomeric form of CtBP for corepression is
      well established, the role of oligomerization in transcriptional coactivation has
      received little attention. Here, we examined the importance of the oligomeric
      state of CtBP for coactivation of NeuroD1-dependent transcription by expressing a
      CtBP dimerization mutant in cells depleted of endogenous CtBP. Dimerization
      mutants failed to increase transcription or to associate with KDM1A and CoREST,
      suggesting that oligomeric, but not monomeric CtBP is required to recruit other
      proteins needed to activate transcription.

PMID- 27880002
TI  - Predictors and Outcomes of Growth Mixture Modeled Trajectories Across an Exposure
      Based PTSD Intervention With Veterans.
AB  - OBJECTIVES: Exposure-based psychotherapies for posttraumatic stress disorder
      (PTSD) are effective for many, but not all patients. It is important to determine
      for whom these treatments work and to examine predictors of success. METHOD: An 8
      week modified prolonged exposure (PE) treatment, including components of
      behavioral activation and reducing the number of imaginal exposure sessions, was
      administered to a sample of 231 Veterans (mean age = 45.7 years, standard
      deviation = 14.89). Growth mixture modeling was used to model PTSD symptom
      trajectories across the 8-week intervention and a postintervention appointment.
      Further, baseline demographics, social support, clinician-rated PTSD symptoms,
      anxiety, and depression were examined as predictors of trajectories. RESULTS:
      Three classes emerged, labeled responders (n = 35), nonresponders (n = 190), and
      immediate responders (n = 6). The only significant baseline difference between
      responders and nonresponders was higher anxiety symptoms in the nonresponders. At
      follow-up time points, there were higher levels of clinician-rated PTSD, anxiety,
      and depression symptoms and lower social support in the nonresponders compared to
      the responders. CONCLUSION: Findings suggest that modifying standard PE
      treatments by reducing imaginal exposure sessions while adding behavioral
      activation may not be advisable for most Veterans with PTSD.

PMID- 27880003
TI  - Association of Multimorbidity with Mortality and Healthcare Utilization in
      Chronic Kidney Disease.
AB  - OBJECTIVES: Chronic kidney disease (CKD) almost universally occurs in individuals
      with other medical problems. However, few studies have described CKD-related
      multimorbidity using a framework that identifies chronic conditions as concordant
      (having overlap in treatment goals) versus discordant (having opposing treatment
      recommendations) and unrelated (having no overlap, but contributing to complexity
      via different resource requirements). DESIGN: Retrospective cohort. SETTING:
      Veterans Affairs (VA) Medical Centers. PARTICIPANTS: VA patients (n = 821,334)
      ages 18-100 years with at least one outpatient visit and incident CKD defined as
      an estimated glomerular filtration rate <60 mL/min/1.73 m2 for at least 3 months
      between January 1, 2005 and December 31, 2008 after excluding prevalent CKD.
      MEASUREMENTS: We determined the associations of number of chronic conditions (1,
      2, 3, 4, 5, 6 or more) stratified by the presence of one or more
      discordant/unrelated conditions with mortality, hospitalizations and emergency
      department (ED) visits. RESULTS: There were 381,187 deaths over 6.8 median years
      of follow-up. Higher risks of death, hospitalization and ED visits were
      associated with higher number of chronic conditions, among those with and without
      discordant/unrelated conditions. However, the magnitudes of the associations were
      consistently larger when at least one discordant/unrelated condition was present.
      For example, compared to patients with one concordant condition, patients with
      six or more concordant conditions had an age-, race- and sex-adjusted hazard
      ratio (HR) for mortality of 1.72 (95% CI 1.64-1.80) whereas those with six or
      more conditions, at least one of which was discordant/unrelated, had a HR of 2.05
      (2.01-2.09) (P-interaction <0.001). CONCLUSIONS: The presence of one or more
      discordant/unrelated conditions was associated with increased risk for adverse
      health outcomes, beyond the effect of multimorbidity.

PMID- 27880005
TI  - S-nitrosoglutathione promotes cell wall remodelling, alters the transcriptional
      profile and induces root hair formation in the hairless root hair defective 6
      (rhd6) mutant of Arabidopsis thaliana.
AB  - Nitric oxide (NO) exerts pleiotropic effects on plant development; however, its
      involvement in cell wall modification during root hair formation (RHF) has not
      yet been addressed. Here, mutants of Arabidopsis thaliana with altered root hair
      phenotypes were used to assess the involvement of S-nitrosoglutathione (GSNO),
      the primary NO source, in cell wall dynamics and gene expression in roots induced
      to form hairs. GSNO and auxin restored the root hair phenotype of the hairless
      root hair defective 6 (rhd6) mutant. A positive correlation was observed between
      increased NO production and RHF induced by auxin in rhd6 and transparent testa
      glabra (ttg) mutants. Deposition of an epitope within rhamnogalacturonan-I
      recognized by the CCRC-M2 antibody was delayed in root hair cells (trichoblasts)
      compared with nonhair cells (atrichoblasts). GSNO, but not auxin, restored the
      wild-type root glycome and transcriptome profiles in rhd6, modulating the
      expression of a large number of genes related to cell wall composition and
      metabolism, as well as those encoding ribosomal proteins, DNA and histone
      modifying enzymes and proteins involved in post-translational modification. Our
      results demonstrate that NO plays a key role in cell wall remodelling in
      trichoblasts and suggest that it also participates in chromatin modification in
      root cells of A. thaliana.

PMID- 27880004
TI  - Causal relationships between neurons of the nucleus incertus and the hippocampal
      theta activity in the rat.
AB  - KEY POINTS: The nucleus incertus is a key node of the brainstem circuitry
      involved in hippocampal theta rhythmicity. Synchronisation exists between the
      nucleus incertus and hippocampal activities during theta periods. By the Granger
      causality analysis, we demonstrated a directional information flow between theta
      rhythmical neurons in the nucleus incertus and the hippocampus in theta-on
      states. The electrical stimulation of the nucleus incertus is also able to evoke
      a phase reset of the hippocampal theta wave. Our data suggest that the nucleus
      incertus is a key node of theta generation and the modulation network. ABSTRACT:
      In recent years, a body of evidence has shown that the nucleus incertus (NI), in
      the dorsal tegmental pons, is a key node of the brainstem circuitry involved in
      hippocampal theta rhythmicity. Ascending reticular brainstem system activation
      evokes hippocampal theta rhythm with coupled neuronal activity in the NI. In a
      recent paper, we showed three populations of neurons in the NI with differential
      firing during hippocampal theta activation. The objective of this work was to
      better evaluate the causal relationship between the activity of NI neurons and
      the hippocampus during theta activation in order to further understand the role
      of the NI in the theta network. A Granger causality analysis was run to determine
      whether hippocampal theta activity with sensory-evoked theta depends on the
      neuronal activity of the NI, or vice versa. The analysis showed causal
      interdependence between the NI and the hippocampus during theta activity, whose
      directional flow depended on the different neuronal assemblies of the NI. Whereas
      type I and II NI neurons mainly acted as receptors of hippocampal information,
      type III neuronal activity was the predominant source of flow between the NI and
      the hippocampus in theta states. We further determined that the electrical
      activation of the NI was able to reset hippocampal waves with enhanced theta-band
      power, depending on the septal area. Collectively, these data suggest that
      hippocampal theta oscillations after sensory activation show dependence on NI
      neuron activity, which could play a key role in establishing optimal conditions
      for memory encoding.

PMID- 27880006
TI  - Impairing both HMA4 homeologs is required for cadmium reduction in tobacco.
AB  - In tobacco, the heavy metal P1B-ATPases HMA4.1 and HMA4.2 function in root-to
      shoot zinc and cadmium transport. We present greenhouse and field data that
      dissect the possibilities to impact the two homeologous genes in order to define
      the best strategy for leaf cadmium reduction. In a first step, both genes were
      silenced using an RNAi approach leading to >90% reduction of leaf cadmium
      content. To modulate HMA4 function more precisely, mutant HMA4.1 and HMA4.2
      alleles of a Targeting Induced Local Lesions IN Genomes (TILLING) population were
      combined. As observed with RNAi plants, knockout of both homeologs decreased
      cadmium root-to-shoot transfer by >90%. Analysis of plants with segregating null
      and wild-type alleles of both homeologs showed that one functional HMA4 allele is
      sufficient to maintain wild-type cadmium levels. Plant development was affected
      in HMA4 RNAi and double knockout plants that included retarded growth, necrotic
      lesions, altered leaf morphology and increased water content. The combination of
      complete functional loss (nonsense mutation) in one homeologous HMA4 gene and the
      functional reduction in the other HMA4 gene (missense mutation) is proposed as
      strategy to limit cadmium leaf accumulation without developmental effects.

PMID- 27880007
TI  - Benefits from living together? Clades whose species use similar habitats may
      persist as a result of eco-evolutionary feedbacks.
AB  - Contents 66 I. 67 II. 68 III. 69 IV. 70 V. 73 VI. 75 VII. 77 78 References 78
      SUMMARY: Recent decades have seen declines of entire plant clades while other
      clades persist despite changing environments. We suggest that one reason why some
      clades persist is that species within these clades use similar habitats, because
      such similarity may increase the degree of co-occurrence of species within
      clades. Traditionally, co-occurrence among clade members has been suggested to be
      disadvantageous because of increased competition and enemy pressure. Here, we
      hypothesize that increased co-occurrence among clade members promotes mutualist
      exchange, niche expansion or hybridization, thereby helping species avoid
      population decline from environmental change. We review the literature and
      analyse published data for hundreds of plant clades (genera) within a well
      studied region and find major differences in the degree to which species within
      clades occupy similar habitats. We tentatively show that, in clades for which
      species occupy similar habitats, species tend to exhibit increased co-occurrence,
      mutualism, niche expansion, and hybridization - and rarely decline. Consistently,
      throughout the geological past, clades whose species occupied similar habitats
      often persisted through long time-spans. Overall, for many plant species, the
      occupation of similar habitats among fellow clade members apparently reduced
      their vulnerability to environmental change. Future research should identify when
      and how this previously unrecognized eco-evolutionary feedback operates.

PMID- 27880008
TI  - Head and neck surgical subspecialty training in Africa: Sustainable models to
      improve cancer care in developing countries.
AB  - BACKGROUND: Cancer poses a health crisis in the developing world where surgery is
      the mainstay of treatment for head and neck cancers. However, a shortage of
      surgeons with appropriate skills exists. How do we train head and neck surgeons
      in developing countries and avoid a brain drain? The ideal model provides
      appropriate affordable training leading to establishment of head and neck cancer
      centers that teach and train others. METHODS: Different head and neck surgery
      training models are presented based on the personal experiences of the authors.
      Surgical exposure of head and neck fellows in Cape Town and (potentially) in
      Nairobi is benchmarked against programs in the United States. RESULTS: Surgical
      exposure in Cape Town is equivalent to that in the United States, but more
      appropriate to a developing world setting. CONCLUSION: Training can be achieved
      in a number of ways, which may be complimentary. Fellowship training is possible
      in developing countries. (c) 2016 Wiley Periodicals, Inc. Head Neck 39: 605-611,
      2017.

PMID- 27880009
TI  - Antianginal Efficacy of Ivabradine/Metoprolol Combination in Patients With Stable
      Angina.
AB  - Medical treatment is the main clinical strategy for controlling patients with
      chronic stable angina and improving their quality of life (QoL). Ivabradine
      treatment on top of metoprolol decreases angina symptoms and improves QoL in
      patients with stable angina and coronary artery disease (CAD). This is a post hoc
      analysis (636 CAD patients given ivabradine/metoprolol free combination) of a
      prospective, noninterventional study that included 2403 patients with CAD and
      stable angina. Data were recorded at baseline at 1 and 4 months after inclusion.
      Patient QoL was assessed using the EQ-5D questionnaire. From baseline to study
      completion; ivabradine administration on top of metoprolol decreased heart rate
      (HR) from 80.8 +/- 9.6 to 64.2 +/- 6.2 bpm (P < 0.001). Mean number of angina
      attacks decreased from 2.0 +/- 2.0/wk to 0.2 +/- 0.6/wk (P < 0.001), whereas
      nitroglycerin consumption decreased from 1.4 +/- 1.9 times/wk to 0.1 +/- 0.4
      times/wk (P < 0.001). The percentage of patients in Canadian Cardiovascular
      Society angina class III to IV decreased from 15.4% to 1.9% (P < 0.001). The
      improvement of symptoms and angina class led to a significant 14.7-point increase
      in EQ-5D questionnaire score (P < 0.001). Patients with increased HR showed
      greater improvement (P = 0.001). Adherence to treatment during the entire trial
      was high (98%). Ivabradine combined with metoprolol significantly decreased
      angina symptoms and use of nitroglycerin in patients with stable angina and CAD,
      leading to improved QoL. The benefits observed with this combination explain the
      high rate of adherence to treatment.

PMID- 27880010
TI  - Abnormal baseline brain activity in Parkinson's disease with and without REM
      sleep behavior disorder: A resting-state functional MRI study.
AB  - PURPOSE: To investigate the differences in spontaneous brain activity between
      Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder
      (RBD), PD patients without RBD, and normal controls, which may shed new light on
      the neural mechanism of RBD. MATERIALS AND METHODS: Eighteen PD patients with
      RBD, 16 patients without RBD, and 19 age- and gender-matched normal controls
      underwent clinical assessment and functional magnetic resonance imaging (fMRI)
      with a 3.0T scanner. Resting-state fMRI scans were collected using an echo planar
      imaging sequence. Amplitude of low-frequency fluctuations (ALFF) were calculated
      to measure spontaneous brain activity in each subject. RESULTS: Compared with PD
      patients without RBD, patients with RBD exhibited significantly decreased ALFF
      values (P < 0.001, cluster level) in primary motor cortex extending to premotor
      cortex. Compared with normal controls, PD patients exhibited decreased ALFF
      values (P < 0.001, cluster level) in caudate and putamen (P < 0.001, cluster
      level), and increased ALFF values (P = 0.03, cluster level) in prefrontal cortex.
      CONCLUSION: The altered spontaneous brain activity in motor cortex may contribute
      to the pathogenesis of RBD in PD patients, which further supports the idea that
      the pathophysiology of RBD involves not only midbrain dysfunction but also
      cerebral cortex abnormalities. Our findings provide additional insight into the
      neural mechanism of RBD and may drive future research to develop better
      treatment. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. MAGN. RESON.
      IMAGING 2017;46:697-703.

PMID- 27880011
TI  - Shear Bond Strength of Repair Systems to New CAD/CAM Restorative Materials.
AB  - PURPOSE: To evaluate the bond strength of repair systems (Ceramic Repair,
      Clearfil Repair) to computer-aided design/computer-assisted machining (CAD/CAM)
      restorative materials (IPS e.max CAD, Vita Suprinity, Vita Enamic, Lava
      Ultimate). MATERIALS AND METHODS: Thermally aged CAD/CAM restorative material
      specimens (5000 cycles between 5 degrees C and 55 degrees C) were randomly
      divided into two groups according to the repair system: Ceramic Repair (37%
      phosphoric acid + Monobond-S + Heliobond + Tetric N Ceram) or Clearfil Repair
      (40% phosphoric acid + mixture of Clearfil Porcelain Bond Activator and Clearfil
      SE Bond Primer + Clearfil SE Bond + Filtek Z250). The resin composite was light
      cured on conditioned specimens. All specimens were stored in distilled water at
      37 degrees C for 24 hours and then additionally aged for 5000 thermal cycles. The
      shear bond strength test was performed using a universal testing machine (0.5
      mm/min). Two-way ANOVA was used to detect significance differences according to
      the CAD/CAM material and composite repair system factors. Subgroup analyses were
      conducted using the least significant difference post-hoc test. RESULTS: The
      results of two-way ANOVA indicated that bond strength values varied according to
      the restorative materials (p < 0.05). No significant differences were observed
      between the CAD/CAM restorative materials (p > 0.05), except in the Vita
      Suprinity group (p < 0.05). Moreover, no differences were observed between the
      repair systems. CONCLUSIONS: Both the Clearfil and Ceramic repair systems used in
      the study allow for successful repairs.

PMID- 27880012
TI  - Patterns of gene expression in developing embryos of Arabidopsis hybrids.
AB  - Hybrids between the Arabidopsis ecotypes C24 and Ler have high levels of hybrid
      vigour, or heterosis, in both biomass and seed yield. Heterosis can be detected
      throughout the development of the plant and in different tissues. We examined
      developing embryos and seeds of C24/Ler reciprocal hybrids with the aim of
      detecting the earliest time at which heterotic gene activity occurs. In the
      transcriptomes of 4-dap (days after pollination; dermatogen to globular) and 6
      dap (heart) embryos from both parents and hybrids, 95% of expressed genes were at
      the mid parent value (MPV) and 95% of the genes with single nucleotide
      polymorphisms between C24 and Ler retained the same relative allelic expression
      levels in the hybrids as existed in the parents. This included loci that had
      equivalent levels of transcription in the two parents, together with loci which
      had different levels of expression in the parents. Amongst the genes which did
      not have MPV expression levels in the hybrids (non-additively expressed genes),
      approximately 40 in the globular embryo stage and 89 in the heart embryo stage
      had altered levels of transcription in both reciprocal hybrids; these genes could
      contribute to the heterotic phenotype of the hybrid embryo. Many of the non
      additively expressed genes had expression levels that were shifted towards
      maternal levels of transcription, and these differed in the reciprocal hybrids.
      Allelic expression analysis indicated that most genes with altered allelic
      contributions in the hybrids had an increase in the expression level of the
      hybrid's maternal allele. Consistent with the maternal pattern of gene
      expression, embryo and seed also show maternally influenced phenotypes.

PMID- 27880013
TI  - On-Demand Release of Hydrosoluble Drugs from a Paramagnetic Porous Collagen-Based
      Scaffold.
AB  - The design of a collagen scaffold containing iron oxide nanostructures capped by
      a TiO2 (anatase) layer is reported. The TiO2 shell is proposed to perform a dual
      role: 1) as an innovative and biocompatible cross-linker agent, providing binding
      sites to the protein moiety, through the well-known TiO2 chemical affinity
      towards carboxyl groups, and 2) as a protective surface layer for the
      paramagnetic core against oxidation. Simultaneously, the presence of the
      nanostructures confers to the collagen gel sensitivity to an external stimulus;
      that is, the application of a magnetic field. The hybrid biomaterial was
      demonstrated to be nontoxic and is proposed as a smart scaffold for the release
      of bioactive compounds on demand. The tuneable release of a model protein
      (myoglobin) upon application of a magnetic field was investigated. Myoglobin was
      loaded in the microporous material and discharge was induced by consecutive
      magnet applications, leading to release of the protein with high spatio-temporal
      and dosage control.

PMID- 27880014
TI  - Inhibition of epithelial-mesenchymal transition by cetuximab via the EGFR-GEP100
      Arf6-AMAP1 pathway in head and neck cancer.
AB  - BACKGROUND: Despite improved survival by the addition of a monoclonal antibody
      against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or
      radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab
      by itself is not a potent antiproliferative agent against SCCHN. We aimed to
      elucidate working mechanism of cetuximab in SCCHN. METHODS: The effect of
      cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal
      transition, and signaling events downstream of the EGFR were investigated in 4
      SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a
      xenotransplant model. RESULTS: Cetuximab inhibited migration, invasion,
      epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR
      GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation.
      CONCLUSION: The improved survival by the addition of cetuximab is likely to be
      attributable to the antiepithelial-mesenchymal transition action of cetuximab via
      inhibiting EGFR-GEP100-Arf6-AMAP1 pathway. (c) 2016 Wiley Periodicals, Inc. Head
      Neck 39: 476-485, 2017.

PMID- 27880015
TI  - Bifunctional Molecular Photoswitches Based on Overcrowded Alkenes for Dynamic
      Control of Catalytic Activity in Michael Addition Reactions.
AB  - The emerging field of artificial photoswitchable catalysis has recently shown
      striking examples of functional light-responsive systems allowing for dynamic
      control of activity and selectivity in organocatalysis and metal-catalysed
      transformations. While our group has already disclosed systems featuring first
      generation molecular motors as the switchable central core, a design based on
      second generation molecular motors is lacking. Here, the syntheses of two
      bifunctionalised molecular switches based on a photoresponsive tetrasubstituted
      alkene core are reported. They feature a thiourea substituent as hydrogen-donor
      moiety in the upper half and a basic dimethylamine group in the lower half. This
      combination of functional groups offers the possibility for application of these
      molecules in photoswitchable catalytic processes. The light-responsive central
      cores were synthesized by a Barton-Kellogg coupling of the prefunctionalized
      upper and lower halves. Derivatization using Buchwald-Hartwig amination and
      subsequent introduction of the thiourea substituent afforded the target
      compounds. Control of catalytic activity in the Michael addition reaction between
      (E)-3-bromo-beta-nitrostyrene and 2,4-pentanedione is achieved upon irradiation
      of stable-(E) and stable-(Z) isomers of the bifunctional catalyst 1. Both isomers
      display a decrease in catalytic activity upon irradiation to the metastable
      state, providing systems with the potential to be applied as ON/OFF catalytic
      photoswitches.

PMID- 27880016
TI  - Reactions Catalysed by a Binuclear Copper Complex: Relay Aerobic Oxidation of N
      Aryl Tetrahydroisoquinolines to Dihydroisoquinolones with a Vitamin B1 Analogue.
AB  - N-Aryl tetrahydroisoquinolines were oxidised to dihydroisoquinolones through the
      relay catalysis of a binuclear paddle-wheel copper complex and a vitamin B1
      analogue with oxygen as oxidant. Mechanistic studies revealed that the copper
      catalyst oxidises amines to the corresponding iminium salts, which are then
      oxygenated to lactam products by catalysis of the vitamin B1 analogue.

PMID- 27880017
TI  - Comparison of the outcomes of free jejunal flap reconstructions of
      pharyngoesophageal defects in hypopharyngeal cancer and corrosive injury
      patients.
AB  - INTRODUCTION: Free jejunal flap is one of the optimal choices for restoring upper
      digestive tract. The purpose of this study was to introduce the treatment
      strategies and to compare the outcomes of free jejunal flap for
      pharyngoesophageal reconstruction between hypopharyngeal cancer and chemical
      corrosive injured esophagus. METHODS: From 2001 to 2012, patients who had been
      received esophageal reconstruction by free jejunal flap for pharyngoesophageal
      defect were divided into squamous cell carcinoma (SCC) group and corrosive
      chemical injury (CCI) group. All data on outcomes and complications including
      relevant radiographic investigations were collected retrospectively. RESULTS:
      Sixteen patients were in SCC group and 9 patients in CCI group underwent free
      jejunal flap reconstruction. Two cases of flap failure were noted in SCC group,
      and no flap failure in CCI group-the total failure rate was 8% (2/25 patients).
      In SCC group, 5 of 16 patients (31.3%) developed fistula; however, no fistula in
      CCI group. One patient in SCC group and 3 patients in CCI group developed
      esophageal strictures. Other than early stricture (stricture <1 year) which
      reached significant difference, all of other complications were not statistically
      significant between two groups. The average follow-up time was 42 months.
      CONCLUSIONS: Postoperative early stricture but lower fistula occurrence is
      expected in patients with corrosively injured esophagi. This helpful preliminary
      findings could not only early-check complication, but also better explanation and
      prepare were taken placed before operation.

PMID- 27880018
TI  - Drought-related secondary metabolites of barley (Hordeum vulgare L.) leaves and
      their metabolomic quantitative trait loci.
AB  - Determining the role of plant secondary metabolites in stress conditions is
      problematic due to the diversity of their structures and the complexity of their
      interdependence with different biological pathways. Correlation of metabolomic
      data with the genetic background provides essential information about the
      features of metabolites. LC-MS analysis of leaf metabolites from 100 barley
      recombinant inbred lines (RILs) revealed that 98 traits among 135 detected
      phenolic and terpenoid compounds significantly changed their level as a result of
      drought stress. Metabolites with similar patterns of change were grouped in
      modules, revealing differences among RILs and parental varieties at early and
      late stages of drought. The most significant changes in stress were observed for
      ferulic and sinapic acid derivatives as well as acylated glycosides of flavones.
      The tendency to accumulate methylated compounds was a major phenomenon in this
      set of samples. In addition, the polyamine derivatives hordatines as well as
      terpenoid blumenol C derivatives were observed to be drought related. The
      correlation of drought-related compounds with molecular marker polymorphisms
      resulted in the definition of metabolomic quantitative trait loci in the genomic
      regions of single-nucleotide polymorphism 3101-111 and simple sequence repeat
      Bmag0692 with multiple linkages to metabolites. The associations pointed to genes
      related to the defence response and response to cold, heat and oxidative stress,
      but not to genes related to biosynthesis of the compounds. We postulate that the
      significant metabolites have a role as antioxidants, regulators of gene
      expression and modulators of protein function in barley during drought.

PMID- 27880020
TI  - Reactions Catalysed by a Binuclear Copper Complex: Aerobic Cross Dehydrogenative
      Coupling of N-Aryl Tetrahydroisoquinolines.
AB  - Binuclear copper complex [{Cu(Sal)2 (NCMe)}2 ] (Sal=salicylate) was found to be
      an active catalyst for the aerobic oxidation of N-aryl tetrahydroisoquinolines to
      the corresponding iminium ions, which could be trapped by a wide range of
      nucleophiles to form coupled products. The reactions took place under 1 bar of O2
      at room temperature with 1 mol % of the copper catalyst being sufficient in most
      cases, and are considerably accelerated by catalytic chloride anions. Mechanistic
      studies show that the CuII dimer oxidizes the amine to the iminium ion, and this
      two-electron process requires O2 , whereby the resulting CuI is concomitantly
      reoxidised back to CuII . Various lines of evidence suggest that the oxidative
      coupling reaction is turnover-limited by the step of iminium formation, and it is
      this step that is promoted by the chloride anion. Since it is more efficient than
      and mechanistically distinct from the well-studied simple copper salts such as
      CuBr and CuCl2 , the binuclear copper catalyst provides a new tool for oxidative
      coupling reactions.

PMID- 27880019
TI  - Inferential and forward projection modeling to evaluate options for controlling
      invasive mammals on islands.
AB  - Successful pest-mammal eradications from remote islands have resulted in
      important biodiversity benefits. Near-shore islands can also serve as refuges for
      native biota but require ongoing effort to maintain low-pest or pest-free status.
      Three management options are available in the presence of reinvasion risk: (1)
      control-to-zero density, in which immigration may occur but reinvaders are
      removed; (2) sustained population suppression (to relatively low numbers); or (3)
      no action. Biodiversity benefits can result from options one and two. The
      management challenge is to make evidence-based decisions on the selection of an
      appropriate objective and to identify a financially feasible control strategy
      that has a high probability of success. This requires understanding the pest
      species population dynamics and how it will respond to a range of potential
      management strategies, each with an associated financial cost. We developed a two
      stage modeling approach that consisted of (1) Bayesian inferential modeling to
      estimate parameters for a model of pest population dynamics and control, and (2)
      a forward projection model to simulate a range of plausible management scenarios
      and quantify the probability of obtaining zero density within four years. We
      applied the model to an ongoing, six-year trapping program to control stoats
      (Mustela erminea) on Resolution Island, New Zealand. Zero density has not yet
      been achieved. Results demonstrate that management objectives were impeded by a
      combination of a highly fecund population, insufficient trap attractiveness, and
      a substantial proportion of the population that did not enter traps. Immigration
      is known to occur because the founding population arrived on the island by
      swimming from the mainland. However, immigration rate during this study was
      indistinguishable from zero. The forward projection modeling showed that control
      to-zero density was feasible but required greater than a two-fold budget increase
      to intensify the trapping rate relative to population growth. The two-stage
      modeling provides the foundation for a management program in which broad-scale
      trials of additional trapping effort or improved trap lures would test model
      predictions and increase our understanding of system dynamics.

PMID- 27880021
TI  - Engineering the expression level of cytosolic nucleoside diphosphate kinase in
      transgenic Solanum tuberosum roots alters growth, respiration and carbon
      metabolism.
AB  - Nucleoside diphosphate kinase (NDPK) is a ubiquitous enzyme that catalyzes the
      transfer of the gamma-phosphate from a donor nucleoside triphosphate to an
      acceptor nucleoside diphosphate. In this study we used a targeted metabolomic
      approach and measurement of physiological parameters to report the effects of the
      genetic manipulation of cytosolic NDPK (NDPK1) expression on physiology and
      carbon metabolism in potato (Solanum tuberosum) roots. Sense and antisense NDPK1
      constructs were introduced in potato using Agrobacterium rhizogenes to generate a
      population of root clones displaying a 40-fold difference in NDPK activity. Root
      growth, O2 uptake, flux of carbon between sucrose and CO2 , levels of reactive
      oxygen species and some tricarboxylic acid cycle intermediates were positively
      correlated with levels of NDPK1 expression. In addition, NDPK1 levels positively
      affected UDP-glucose and cellulose contents. The activation state of ADP-glucose
      pyrophosphorylase, a key enzyme in starch synthesis, was higher in antisense
      roots than in roots overexpressing NDPK1. Further analyses demonstrated that ADP
      glucose pyrophosphorylase was more oxidized, and therefore less active, in sense
      clones than antisense clones. Consequently, antisense NDPK1 roots accumulated
      more starch and the starch to cellulose ratio was negatively affected by the
      level of NDPK1. These data support the idea that modulation of NDPK1 affects the
      distribution of carbon between starch and cellulose biosynthetic pathways.

PMID- 27880022
TI  - Active commuting to school was inversely associated with academic achievement in
      primary but not secondary school students.
AB  - AIM: Physical activity has numerous benefits for children when it comes to
      academic achievements. This study determined whether active commuting - walking
      or cycling - to school, as a way of increasing total physical activity levels,
      was associated with academic achievements in students aged seven to 18 years.
      METHODS: A total of 2138 students participated in the study, which took place in
      the 2012/2013 academic year in three Spanish cities. We used a self-reported
      questionnaire to assess how the students travelled to and from school and their
      final school grades. RESULTS: We enrolled 489 primary schoolchildren and 1649
      secondary schoolchildren, with similar numbers of boys and girls. The primary
      schoolchildren who travelled to school by motorbike, car or bus had better grades
      for all the selected school subjects (p <= 0.009) than those who walked or
      cycled. No significant associations were found for secondary schoolchildren,
      except for mathematics and their grade point averages. All models were adjusted
      for sex, age and school. CONCLUSION: Active commuting to school was inversely
      associated with academic achievement in primary school students but not those at
      secondary school. Longitudinal and intervention studies are needed to further
      understand our findings.

PMID- 27880023
TI  - Effect of Cyclic Fatigue Tests on Aging and Their Translational Implications for
      Survival of All-Ceramic Tooth-Borne Single Crowns and Fixed Dental Prostheses.
AB  - PURPOSE: The objective of this systematic review was to elaborate the aging
      effect of cyclic fatigue tests on mechanical durability of all-ceramic single
      crowns and fixed dental prostheses (FDP). MATERIALS AND METHODS: Original
      scientific papers published in the MEDLINE (PubMed) database in English between
      01/01/1950 and 12/31/2013 on cyclic loading on all-ceramics were included in this
      systematic review. The following MeSH terms, search terms, and their combinations
      were used: "in vitro," "stress mechanical," "crowns," "denture, partial, fixed,"
      "dentistry," "fatigue," "all-ceramic," "zirconia," "fixed dental prosthesis,"
      "FDP," "bridges," and "cyclic loading." Two reviewers performed screening and
      analyzed the data. Only the studies that reported on both static fracture
      strength and static fracture after fatigue of all-ceramic single crowns and FDPs
      that allowed comparison of aging effect through cyclic loading were included.
      RESULTS: The selection process resulted in a final sample of 14 journal articles.
      In total, 9 articles were identified related to all-ceramic single crowns, 3 of
      which were on anterior and 6 on posterior crowns, and 5 articles on 3-unit FDPs,
      all of which were on posterior FDPs. Fatigue cycles varied between minimum of
      1000 to maximum 1,200,000 cycles for crowns and 10,000 to 2,000,000 cycles for 3
      unit FDPs. The applied force during cyclic loading varied between 20 to 300 N for
      single crowns and 49 to 200 N for 3-unit FDPs. For the 3-unit FDPs, fracture
      strength results showed slightly decreased values after cyclic loading (659 +/-
      182 to 2333 +/- 183 N) compared to static loading only (841 +/- 244 to 2434 +/-
      154 N). For crowns similar trends were not observed, but cyclic loading decreased
      the fracture strength in only some materials after cyclic loading (659 +/- 182 to
      2333 +/- 183 N) compared to static loading only (395 +/- 96 to 2726 N).
      CONCLUSIONS: An inclination for decreased static fracture strength could be
      observed after cyclic loading of all-ceramic single crowns and FDPs, but this was
      material specific. Due to the heterogeneity of data such as aging, loading
      conditions, and fewer experimental groups, statistical analysis could not be
      performed. Cyclic loading tests require more standardized guidelines for testing
      and reporting.

PMID- 27880024
TI  - Insect cold hardiness: the role of mitogen-activated protein kinase and Akt
      signalling in freeze avoiding larvae of the goldenrod gall moth, Epiblema
      scudderiana.
AB  - Larvae of the goldenrod gall moth, Epiblema scudderiana, use the freeze avoidance
      strategy of cold hardiness to survive the winter. Here we report that protein
      kinase-dependent signal transduction featuring mitogen-activated protein kinase
      (MAPK) signalling cascades (extracellular signal regulated kinase, c-jun N
      terminal kinase and p38 MAPK pathways) and the Akt (also known as protein kinase
      B, or PKB) pathway could be integral parts of the development of cold hardiness
      by E. scudderiana. We used Luminex technology to assess the protein levels and
      phosphorylation status of key components and downstream targets of those pathways
      in larvae in response to low temperature acclimation. The data showed that MAPK
      pathways (both total protein and phosphorylated MAPK targets) were inhibited
      after 5 degrees C acclimation, but not -15 degrees C exposure, as compared with
      the 15 degrees C control group. However, total heat shock protein 27 (HSP27)
      levels increased dramatically by ~12-fold in the -15 degrees C acclimated
      insects. Elevated HSP27 may facilitate anti-apoptotic mechanisms in an Akt
      dependent fashion. By contrast, both 5 and -15 degrees C acclimation produced
      signs of Akt pathway activation. In particular, the inhibitor phosphorylated
      Glycogen Synthase Kinase 3a (p-GSK3) levels remained high in cold-exposed larvae.
      Additionally, activation of the Akt pathway might also facilitate inhibition of
      apoptosis independently of GSK3. Overall, the current study indicates that both
      MAPK and Akt signal transduction may play essential roles in freeze avoidance by
      E. scudderiana.

PMID- 27880025
TI  - Attitudes towards decisions about extremely premature infants differed between
      Swiss linguistic regions in population-based study.
AB  - AIM: Studies have provided insights into the different attitudes and values of
      healthcare professionals and parents towards extreme prematurity. This study
      explored societal attitudes and values in Switzerland with regard to this patient
      group. METHODS: A nationwide trilingual telephone survey was conducted in the
      French-, German- and Italian-speaking regions of Switzerland to explore the
      general population's attitudes and values with regard to extreme prematurity.
      Swiss residents of 18 years or older were recruited from the official telephone
      registry using quota sampling and a logistic regression model assessed the
      influence of socio-demographic factors on end-of-life decision-making. RESULTS:
      Of the 5112 people contacted, 1210 (23.7%) participated. Of these 5% were the
      parents of a premature infant and 26% knew parents with a premature infant. Most
      participants (77.8%) highlighted their strong preference for shared decision
      making, and 64.6% said that if there was dissent then the parents should have the
      final word. Overall, our logistic regression model showed that regional
      differences were the most significant factors influencing decision-making.
      CONCLUSION: The majority of the Swiss population clearly favoured shared decision
      making. The context of sociocultural demographics, especially the linguistic
      region in which the decision-making took place, strongly influenced attitudes
      towards extreme prematurity and decision-making.

PMID- 27880027
TI  - A Simple Technique for Placing Extraoral Implants at an Optimal Position in
      Orbital Defects.
AB  - Translucent acrylic templates have been used to indicate implant positions for
      implant-retained extraoral prostheses; however, this procedure can be
      challenging, as the acrylic templates have to be positioned onto reflected skin
      flaps. The fabrication of an acrylic-based colorless template or duplicating an
      existing prosthesis can facilitate the location of extraoral implants. Spots can
      be created on templates to indicate the optimal position of the implants.
      Afterward, punching the skin to the bone with a very thick sharp needle or a
      small sharp bur will mark the desired implant position on the bone before
      reflecting the skin.

PMID- 27880026
TI  - The cryptic Cryptococcus.

PMID- 27880028
TI  - Effect of Different Surface Treatments on Bond Strength of Resin Cement to a
      CAD/CAM Restorative Material.
AB  - PURPOSE: To investigate the effects of various surface treatment methods on the
      shear bond strength of self-adhesive resin cement to a novel CAD/CAM hybrid
      ceramic material. MATERIALS AND METHODS: A novel hybrid ceramic restorative
      material (Vita Enamic) was used in this study. Sixty resin block specimens were
      prepared and separated into six groups for each surface treatment method (n =
      10); group 1: control group, no treatment applied; group 2: sandblasted by 30 MUm
      silicate-coated alumina particles (CoJet Sandblasting); group 3: 50 MUm Al2 O3
      sandblasting; group 4: 10% hydrofluoric acid; group 5: no surface treatment +
      universal adhesive (3M Single Bond Universal); group 6: 200 mJ, 10 Hz 2W
      Er,Cr:YSGG laser treatment. For each specimen, surface roughness measurements in
      noncontact mode were taken after the surface treatments using a portable surface
      texture-measuring machine. A self-adhesive resin cement (3M U200) was applied on
      every surface treated with the help of a cylindrical mold (2 * 4 mm) and was
      filled gradually. Shear bond strength was measured using a universal test
      machine, and one-way ANOVA and a Duncan test (p = 0.05) were used to analyze the
      data. RESULTS: Mean values of the shear bond strength varied between 7.75 and
      10.73 MPa. Bond strength values were enhanced by all surface treatment methods
      compared to the control group. The difference between group 5 and the control
      group (p < 0.05) was statistically significant, whereas there were no
      considerable differences between other treatment methods. CONCLUSION: Surface
      treatments of hybrid ceramic resin blocks could enhance the bond strength to
      resin cement; however, using Single Bond Universal without surface treatment
      showed a higher bond strength value.

PMID- 27880029
TI  - Hypertension, haematuria and renal functioning in haemophilia - a cross-sectional
      study in Europe.
AB  - BACKGROUND AND OBJECTIVES: This cross-sectional, epidemiological study sought to
      assess the prevalence and extent of potential risk factors for hypertension,
      particularly renal function related to haematuria and their associations in
      people with haemophilia. METHODOLOGY: Demographic and medical data were collected
      at a single time-point in patients with haemophilia over 40 years of age from 16
      European centres. Associations with diagnosis of hypertension were tested in
      univariate and multivariate analyses. RESULTS: We enrolled 532 patients (median
      age 52 years, range 40-98) with haemophilia A (n = 467) or haemophilia B (n =
      65). Haemophilia was severe (<0.01 IU mL-1 ) in 313 patients (59%). Hypertension
      was diagnosed in 239 patients (45%). In multivariate analyses, age and body mass
      index (BMI) were significantly and independently associated with hypertension
      (adjusted odds ratio (OR) 18.1, P < 0.001, in elderly patients and OR = 25.1, P <
      0.001, in patients with BMI >30 kg m-2 ). Estimated glomerular filtration rate
      (eGFR) <70 mL min-1 (OR = 2.7, P = 0.047) was significantly associated with
      hypertension, but mean eGFR was significantly higher for severe than mild
      haemophilia. Further variables with OR > 2.8 were diabetes (OR = 2.8, P = 0.04),
      coronary artery disease (OR = 3.3, P = 0.052) and family history of hypertension
      (OR = 4.4, P < 0.001). Neither severity of haemophilia nor history of haematuria
      was significantly associated with hypertension in univariate or multivariate
      analyses. CONCLUSION: As in the general population, age and BMI were major risk
      factors for hypertension in people with haemophilia. Renal dysfunction was
      associated with hypertension, but the prevalence of renal dysfunction was not
      extensive and furthermore not significantly correlated with haematuria. The
      associations of other variables with hypertension require further studies to
      confirm causal relationships over time.

PMID- 27880030
TI  - Osseointegrated implants into a variety of composite free flaps: A comparative
      analysis.
AB  - BACKGROUND: Significant oral function is often lost after surgical therapy for
      head and neck cancer. The use of osseointegrated implants for reconstruction in
      patients with head and neck surgery has shown to significantly improve the
      quality of life for these patients. Variable success rates range from 99% to 70%.
      METHODS: A retrospective audit of patient records was performed looking at
      cumulative survival of implants. Inclusion criteria were patients who were
      treated at 1 of 2 designated Australian Head and Neck Units and received oral
      osseointegrated implants. RESULTS: Fifty-nine patients were included for
      analysis. One hundred ninety-nine implants were placed into vascularized bone
      grafts (VBGs). There were 11 implant failures with an overall success rate of
      94.5%. There was 1 significant adverse outcome with a pathological fracture of a
      flap after implant placement. Implant success in scapula and iliac crest flaps
      was comparable to fibula flaps. CONCLUSION: Implants placed into VBGs have a
      reasonable success rate in well-selected patients. (c) 2016 Wiley Periodicals,
      Inc. Head Neck 39: 443-447, 2017.

PMID- 27880032
TI  - Zeolite-based, dry formulations for conservation and practical application of
      Paraburkholderia phytofirmans PsJN.
AB  - AIMS: Producing dry, zeolite-based granular and powder inoculants of the Gram
      negative, plant growth-promoting bacterium Paraburkholderia phytofirmans PsJN.
      Key aspects were maintenance of cell viability during desiccation and throughout
      storage at ambient conditions. METHODS AND RESULTS: Twenty additives and
      exopolysaccharide (EPS) produced by PsJN were screened for conserving cell
      viability of PsJN in air-drying and lyophilization. Suitable combinations (e.g.
      skimmed milk + air-drying) increased survival of PsJN up to 100 000-fold and
      maintained it for >7 months. EPS performed as good as skimmed milk during air
      drying, but was second-rank regarding shelf life. Combinations of zeolite,
      skimmed milk and gelatin as a film-forming agent were extruded and processed into
      granules and powders, both displaying relatively stable viability for over 4
      weeks at ambient conditions. Gelatin promoted brittleness of zeolite-based
      inoculants. CONCLUSIONS: Viability of highly sensitive PsJN was successfully
      conserved in dry formulations, taking into account the interplay between carrier,
      protectants, drying method and coating agent. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This is the first study to provide ways of maintaining viability of PsJN
      during desiccation stress and to investigate the applicability of its EPS as a
      protectant, thus ultimately facilitating successful plant inoculation especially
      under field conditions.

PMID- 27880031
TI  - Increased plasma soluble human leukocyte antigen-G in persistent wheezy infants.
AB  - BACKGROUND: Human leukocyte antigen (HLA)-G is a non-classical major
      histocompatibility complex class I antigen characterized by limited polymorphism
      in its coding region, unique tissue expression pattern in physiologic conditions
      and immunomodulatory properties. Recently, the level of soluble (s)HLA-G was
      found to be higher in atopic asthma and allergic rhinitis, but this remains to be
      clarified in wheezy infants. The aim of the present study was therefore to
      investigate sHLA-G in wheezy infants. METHODS: The subjects consisted of infants
      with persistent wheezing and positive modified asthma predictive index (mAPI; n =
      30; persistent group) and those with transient wheezing and negative mAPI (n =
      17; transient group). sHLA-G was measured in plasma using enzyme-linked
      immunosorbent assay. Total immunoglobulin E (IgE) and eosinophil count were
      measured, and skin testing was performed with a battery of 13 antigens with
      appropriate positive and negative controls. RESULTS: sHLA-G was significantly
      higher in the persistent wheezing (positive mAPI) group compared with the
      transient wheezing (negative mAPI) group (P = 0.008). There was no significant
      difference in peripheral blood eosinophil count and total IgE between the groups.
      CONCLUSIONS: The increased sHLA-G in infants with persistent wheeze suggests that
      sHLA-G may be able to be used to distinguish persistent from transient wheeze.
      Further comprehensive studies are needed on this topic.

PMID- 27880033
TI  - A comparative proteomic analysis reveals important proteins for the fertilization
      and early embryonic development of the oyster Crassostrea gigas.
AB  - Molluscan development involves important features that are important to
      understanding not only molluscan ontogeny but also animal evolution. To gain
      insight into the gamete proteome and protein function in fertilization and early
      development, we analyzed the proteomes of unfertilized oocytes and early embryos
      (2/4-cell stage) of the Pacific oyster, Crassostrea gigas. An oocyte reference
      map containing 116 protein spots, of which 69 were identified, revealed a high
      abundance of vitellogenin-derived protein spots. The differentially regulated
      protein spots during fertilization were screened using comparative proteomic
      approaches. In total, 18 differentially regulated protein spots were screened,
      and 15 of these were identified and divided into three groups. The proteins
      belonging to the first group function in energy supply and antioxidation and are
      proposed to ensure successful fertilization by regulating the levels of adenosine
      triphosphate, resisting oxidative stress, and preventing polyspermy. The proteins
      of the second group are associated with protein synthesis and modification,
      reflecting active protein synthesis after fertilization. The three proteins
      belonging to the final group are hypothesized to function in the regulation of
      embryonic development through the establishment of cell polarity and modulation
      of methylation reactions in nuclei. These results will enhance our knowledge of
      molluscan fertilization and development.

PMID- 27880034
TI  - Synthesis of Monoalkyl Glyceryl Ethers by Ring Opening of Glycidol with Alcohols
      in the Presence of Lewis Acids.
AB  - The present work deals with the production of monoalkyl glyceryl ethers (MAGEs)
      through a new reaction pathway based on the reaction of glycidol and alcohols
      catalyzed by Lewis acid-based catalysts. Glycidol is quantitatively converted
      with high selectivity (99 %) into MAGEs under very mild reaction conditions (80 
      degrees C and 0.01 mol % catalyst loading) in only 1 h using Al(OTf)3 or Bi(OTf)3
      as catalyst. The proposed method enhances the choice of possible green synthetic
      approaches for the production of value-added products such as MAGEs.

PMID- 27880035
TI  - Visible-Light-Promoted AuI to AuIII Oxidation in Triazol-5-ylidene Complexes.
AB  - Reaction of triazolium precursors [MIC(CH2 )n - H+ ]I- (n=1-3) with potassium
      hexamethyldisilazane (KHMDS) and AuCl(SMe2 ) generates the gold(I) complexes of
      the type MIC(CH2 )n ?AuI. Visible light exposure of the latter complexes promotes
      a spontaneous disproportionation process rendering gold(III) complexes of the
      type [{MIC(CH2 )n }2 ?AuI2 ]+ I- . Both the AuI and AuIII complex series were
      tested in the catalytic hydrohydrazination of terminal alkynes using hydrazine as
      nitrogen source.

PMID- 27880036
TI  - Protein-phosphotyrosine proteome profiling by superbinder-SH2 domain affinity
      purification mass spectrometry, sSH2-AP-MS.
AB  - Recently, "superbinder" SH2 domain variants with three amino acid substitutions
      (sSH2) were reported to have 100-fold or greater affinity for protein
      phosphotyrosine (pY) than natural SH2 domains. Here we report a protocol in which
      His-tagged Src sSH2 efficiently captures pY-peptides from protease-digested HeLa
      cell total protein extracts. Affinity purification of pY-peptides by this method
      shows little bias for pY-proximal amino acid sequences, comparable to that
      achieved by using antibodies to pY, but with equal or higher yield. Superbinder
      SH2 affinity purification mass spectrometry (sSH2-AP-MS) therefore provides an
      efficient and economical approach for unbiased pY-directed phospho-proteome
      profiling without the use of antibodies.

PMID- 27880037
TI  - Suppressed erythropoietin expression in a nitrofen-induced congenital
      diaphragmatic hernia.
AB  - BACKGROUND: Erythropoietin (EPO), an essential stimulator of erythropoiesis
      produced by the fetal liver, is important both in vascular remodeling and
      modulation of the endothelial response in the pulmonary vasculature. In addition,
      EPO guides alveolar development, along with retinoic acid (RA). EPO is a direct
      target of RA, and the retinoid pathway is altered in the nitrofen-induced
      congenital diaphragmatic hernia (CDH) model. In the present study, we tested the
      hypothesis that the synthesis of EPO is suppressed in a rat model of CDH.
      MATERIALS AND METHODS: Pregnant rats were treated with either nitrofen or vehicle
      on gestational day 9 (D9). Fetuses were sacrificed on D19 and D21 and divided
      into control and CDH groups. Immunohistochemistry and quantitative real-time
      polymerase chain reaction (RT-PCR) were performed to determine the expression of
      EPO in the fetal liver and kidney. We also estimated the expression of EPO
      receptor in the fetal lung. RESULTS: The relative EPO mRNA expression in the
      liver on D19 and in the kidney on D21 were significantly lower in the CDH group
      than in the controls (P = 0.0008 and P = 0.0064, respectively). In addition, the
      results of immunohistochemistry supported the findings from the RT-PCR analysis.
      No significant changes were noted in the expression pattern or EPO receptor
      levels in the fetal lungs of the CDH group compared to the controls. CONCLUSIONS:
      Our results reveal the suppressed EPO synthesis in the CDH fetus, which may
      contribute to the pathogenesis of lung hypoplasia and modification of pulmonary
      vasculature in the CDH rat model. Pediatr Pulmonol. 2017;52:606-615. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27880038
TI  - Excessive vomiting in pregnancy, active component service women, U.S. Armed
      Forces, 2005-2014.
AB  - Up to 80% of women experience some form of nausea and vomiting during pregnancy.
      However, in some women, nausea and vomiting can be excessive and require
      inpatient and/or outpatient treatment. Data were obtained on 149,071 live births
      from 116,510 service women from 1 January 2005 through 31 December 2014. A total
      of 19,175 of the service women with live births had pregnancies complicated by
      excessive vomiting in pregnancy (EVP) and accounted for 20,511 EVP cases (overall
      rate of 13.8%). Mild and severe hyperemesis gravidarum (HG) combined accounted
      for almost two-thirds of the total EVP cases. The slight increase observed in the
      annual rate of EVP between 2005 and 2014 was driven largely by the outpatient
      trend for mild HG. Together, mild and severe HG accounted for three-quarters of
      all hospital bed days for EVP. About one-third of the women with EVP-complicated
      pregnancies had two or more EVP-related medical encounters. A better awareness of
      this medical condition, severity of its symptoms, and their effect on a woman's
      functioning is needed to provide effective interventions that protect a woman's
      health-related functional status.

PMID- 27880039
TI  - Importance of external cause coding for injury surveillance: lessons from
      assessment of overexertion injuries among U.S. Army soldiers in 2014.
AB  - Injuries are a barrier to military medical readiness, and overexertion has
      historically been a leading mechanism of injury among active duty U.S. Army
      soldiers. Details are needed to inform prevention planning. The Defense Medical
      Surveillance System (DMSS) was queried for unique medical encounters among active
      duty Army soldiers consistent with the military injury definition and assigned an
      overexertion external cause code (ICD-9: E927.0-E927.9) in 2014 (n=21,891). Most
      (99.7%) were outpatient visits and 60% were attributed specifically to sudden
      strenuous movement. Among the 41% (n=9,061) of visits with an activity code (ICD
      9: E001-E030), running was the most common activity (n=2,891, 32%); among the 19%
      (n=4,190) with a place of occurrence code (ICD-9: E849.0-E849.9), the leading
      location was recreation/sports facilities (n=1,332, 32%). External cause codes
      provide essential details, but the data represented less than 4% of all injury
      related medical encounters among U.S. Army soldiers in 2014. Efforts to improve
      external cause coding are needed, and could be aligned with training on and
      enforcement of ICD-10 coding guidelines throughout the Military Health System.

PMID- 27880040
TI  - Acetaminophen overdoses, active component, U.S. Armed Forces, 2006-2015.
AB  - Acetaminophen, a drug commonly used to relieve pain and fever, is generally safe
      and effective when used as directed. However, acetaminophen overdose can cause
      serious adverse events, including liver damage and death. From 2006 through 2015,
      a total of 2,588 cases of acetaminophen overdose were identified in active
      component military members. Rates of acetaminophen overdose declined during this
      10-year surveillance period, from 2.2 cases per 10,000 person-years (p-yrs) in
      2006 to 1.2 cases per 10,000 p-yrs in 2015. Rates of overdose were higher among
      females, members of the Army, and service members younger than 25 years of age.
      Despite the apparent decline in acetaminophen overdose in the active component,
      continued surveillance is warranted to monitor this trend.

PMID- 27880041
TI  - Future Directions in Sleep and Developmental Psychopathology.
AB  - It is critical for psychologists to gain a better understanding about the
      intersection between sleep and developmental psychopathology. However, while many
      strive to answer the question of whether sleep causes developmental
      psychopathology, or vice versa, ultimately the relationship between sleep and
      developmental psychopathology is complex and dynamic. This article considers
      future directions in the field of clinical child and adolescent psychology that
      go beyond this mechanistic question, highlighting areas important to address for
      clinicians and researchers who strive to better understand how best to serve
      children and adolescents with developmental psychopathology. Questions are
      presented about what is normal in terms of sleep across development, the role of
      individual variability in terms of sleep needs and vulnerability to sleep loss,
      and how sleep may serve as a risk or resilience factor for developmental
      psychopathology, concluding with considerations for interventions.

PMID- 27880042
TI  - Morus Rubra Extract Induces Cell Cycle Arrest and Apoptosis in Human Colon Cancer
      Cells Through Endoplasmic Reticulum Stress and Telomerase.
AB  - Many studies have reported cytotoxic effects of different Morus species, but
      there have been only limited studies on the cytotoxic effect of Morus rubra. The
      aims of this study were to evaluate the cytotoxic effect of dimethyl sulfoxide
      extract of M. rubra and to investigate, for the first time, its probable
      cytotoxic activity in human colon cancer (WiDr) cells, together with the
      mechanism involved. The cytotoxic activity of extract was determined using MTT
      assay. The mechanism involved in the cytotoxic effect of extract was then
      evaluated in terms of apoptosis, and the cell cycle using flow cytometry,
      mitochondrial membrane potential (MMP) was investigated using the fluorometric
      method, and expression levels of telomerase and C/EBP homologous protein (CHOP)
      were investigated using reverse-transcription PCR (RT-PCR). M. rubra extract
      exhibited moderate selective cytotoxicity on colon cancer cells compared with
      fibroblast cells. Extract induced cell cycle arrest at the G1 phase and apoptosis
      via reduced MMP in WiDr cells. Additionally, M. rubra extract significantly
      repressed telomerase and induced CHOP expressions in WiDr cells. Our results
      demonstrate that targeting telomerase and endoplasmic reticulum stress represents
      a promising strategy in colon cancer therapy, and M. rubra may have considerable
      potential for development as a novel natural product-based anticancer agent.

PMID- 27880043
TI  - MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath
      Condensate in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by progressive and
      irreversible airflow limitation associated with chronic inflammation involving
      cytokines and metalloproteinases (MMPs). MMP-8, MMP-9 and neutrophil elastase
      (NE) are known to be implicated in COPD but the factors influencing activation
      and suppression remain unclear. This study aimed to compare MMP-8, MMP-9 and NE
      in the peripheral blood of COPD patients and controls and to likewise assess
      exhaled breath condensate (EBC) for these MMPs. Peripheral blood micro(mi)RNA139
      5p levels, which may regulate MMPs in COPD, were also measured. Blood and EBC
      were collected from COPD patients (stable and during exacerbations) and healthy
      controls. Expression of mRNA for MMP-8, MMP-9, NE and miRNA-139-5p expression in
      peripheral blood mononuclear cells (PBMCs) was measured using qRT-PCR. MMP-8, MMP
      9 and NE protein in plasma as well as MMP-8 and MMP-9 protein in EBC were
      analysed by enzyme-linked immunoassays. PBMCs from COPD patients showed greater
      expression of mRNA for MMP-8 (p = 0.0004), MMP-9 (p = 0.0023) and NE (p =
      0.0019). PBMC expression of mRNA for NE was significantly higher in COPD
      exacerbations compared to stable cases (p < 0.05). Expression of mRNA for MMP-9
      and NE correlated negatively with spirometry in patients (p < 0.05). Plasma from
      COPD patients showed greater levels of protein for MMP-8 (p = 0.003), MMP-9 (p =
      0.046) and NE (p = 0.018). MMP-8 protein levels were lower in the EBC of COPD
      patients (p < 0.0001). In PBMCs, enhanced expression of mRNA for MMP-9 and NE is
      associated with COPD and may correlate with disease severity and exacerbations.

PMID- 27880044
TI  - Tuberculosis, Airway Obstruction and Mortality in a Finnish Population.
AB  - There is little long-term follow-up data concerning the association between past
      pulmonary tuberculosis (TB), airway obstruction and mortality. We aimed to
      analyse a national health examination survey data from 6701 adult Finns
      undergoing spirometry between 1978 and 1980 (follow-up through 2013). We
      identified TB either through a disease history or by a TB-indicative scar on a
      chest x-ray. We specified obstruction using the lower limit of normal (LLN) and
      classified severity using the Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) stages 1-4. After adjusting for smoking and other confounders,
      past TB associated with obstruction. Compared to non-TB patients, the adjusted
      odds ratio (OR; 95% CI) of obstruction reached 2.21 (1.52-3.21) among patients
      with a scar recorded by one radiologist, 2.48 (1.63-3.78) when recorded by both
      radiologists and 4.59 (2.86-7.37) among patients with a disease history. Among
      those with neither past TB nor obstruction, with past TB only, with an
      obstruction only and with both, we found hazard ratios (HRs; 95% CIs) for
      subsequent mortality of 1.00 (reference), 1.11 (1.03-1.20), 1.62 (1.31-2.00) and
      1.77 (1.45-2.16), adjusted for age, gender, smoking, body mass index (BMI),
      physical activity, education and general health. In conclusion, past TB strongly
      determines obstruction, although on its own quite weakly predicts premature
      death. TB and obstruction combined predict an additive mortality pattern.

PMID- 27880045
TI  - Koelreuteria Formosana Extract Induces Growth Inhibition and Cell Death in Human
      Colon Carcinoma Cells via G2/M Arrest and LC3-II Activation-Dependent Autophagy.
AB  - Autophagy is a self-destructive process that degrades cytoplasmic constituents.
      In our previous study, Koelreuteria formosana ethanolic extract (KFEE), which is
      obtained from natural plants endemic to Taiwan, has inhibited cell metastasis in
      renal carcinoma cells. However, the anticancer effects of KFEE on colon cancer
      remain unclear. In this study, KFEE exerted a strong cytotoxic effect on DLD-1
      and COLO 205 human colorectal cancer cell lines. KFEE effectively inhibited
      cancer cell proliferation, induced G2/M-phase arrest associated with
      downregulaton of cyclin E, cyclin B and cdc25C and upregulation of p21, and
      induced cell death by activating autophagy but did not cause apoptotic cell
      death. Exposed KFEE cells showed increased levels of acridine orange, autophagic
      vacuoles, and LC3-II proteins, which are specific autophagic markers. Bcl-2, p
      Akt, and p-mTOR levels, which have been implicated in autophagic downregulation,
      were decreased after KFEE treatment. Autophagy inhibitor 3-methyladenosine and
      bafilomycin-A1 and genetic silencing of LC3 attenuated KFEE-induced growth
      inhibition. These findings suggested that KFEE causes cytostatic effect through
      autophagy. In xenograft studies, oral administration of KFEE had significantly
      inhibited the tumor growth in nude mice that had received subcutaneous injection
      of DLD-1 cells. KFEE is a promising candidate in phytochemical-based,
      mechanistic, and pathway-targeted cancer prevention strategies.

PMID- 27880046
TI  - Docosahexaenoic Acid-mediated Inhibition of Heat Shock Protein 90-p23 Chaperone
      Complex and Downstream Client Proteins in Lung and Breast Cancer.
AB  - The molecular chaperone, heat shock protein 90 (Hsp90), is a critical regulator
      for the proper folding and stabilization of several client proteins, and is a
      major contributor to carcinogenesis. Specific Hsp90 inhibitors have been designed
      to target the ATP-binding site in order to prevent Hsp90 chaperone maturation.
      The current study investigated the effects of docosahexaenoic acid (DHA; C22:6 n
      3) on Hsp90 function and downstream client protein expression. In vitro analyses
      of BT-474 human breast carcinoma and A549 human lung adenocarcinoma cell lines
      revealed dose-dependent decreases in intracellular ATP levels by DHA treatment,
      resulting in a significant reduction of Hsp90 and p23 association in both cell
      lines. Attenuation of the Hsp90-p23 complex led to the inhibition of Hsp90 client
      proteins, epidermal growth factor receptor 2 (ErbB2), and hypoxia-inducible
      factor 1alpha (HIF-1alpha). Similar results were observed when employing 2
      deoxyglucose (2-DG), confirming that DHA and 2-DG, both independently and
      combined, can disturb Hsp90 molecular chaperone function. In vivo A549 xenograft
      analysis also demonstrated decreased expression levels of Hsp90-p23 association
      and diminished protein levels of ErbB2 and HIF-1alpha in mice supplemented with
      dietary DHA. These data support a role for dietary intervention to improve cancer
      therapy in tumors overexpressing Hsp90 and its client proteins.

PMID- 27880047
TI  - Are Food Advertisements Promoting More Unhealthy Foods and Beverages over Time?
      Evidence from Three Swedish Food Magazines, 1995-2014.
AB  - Unhealthy food in advertising has been suggested as a mediator for the increase
      in diet-related illness. This study quantitatively investigates changes in food
      advertising between 1995 and 2014 in terms of food categories promoted,
      macronutrient content, and percentage of foods classified as heathy or unhealthy
      from a sample of 7,199 ads from three Swedish food magazines. With the exception
      of increased alcoholic beverage and decreased carbohydrate-rich-food promotion,
      no monotonic trends of increasingly unhealthy food advertisement are found. From
      these findings, it is argued that food magazine advertising is not a mediator of
      the adverse dietary trend.

PMID- 27880048
TI  - Using a Few Snapshots to Distinguish Mountains from Waves: Weak Factorial
      Invariance in the Context of Trait-State Research.
AB  - In this article, we show that the underlying dimensions obtained when factor
      analyzing cross-sectional data actually form a mix of within-person state
      dimensions and between-person trait dimensions. We propose a factor analytical
      model that distinguishes between four independent sources of variance: common
      trait, unique trait, common state, and unique state. We show that by testing
      whether there is weak factorial invariance across the trait and state factor
      structures, we can tackle the fundamental question first raised by Cattell; that
      is, are within-person state dimensions qualitatively the same as between-person
      trait dimensions? Furthermore, we discuss how this model is related to other
      trait-state factor models, and we illustrate its use with two empirical data
      sets. We end by discussing the implications for cross-sectional factor analysis
      and suggest potential future developments.

PMID- 27880049
TI  - Understanding clinicians' attitudes toward a mobile health strategy to childhood
      asthma management: A qualitative study.
AB  - OBJECTIVES: Mobile technology for childhood asthma can provide real-time data to
      enhance care. What real-time adherence information clinicians want, how they may
      use it, and if the data meet their clinical needs have not been fully explored.
      Our goal was to determine whether pediatric primary care and pulmonary clinicians
      believe if a sensor-based mobile intervention is useful in caring for patients
      with asthma. METHODS: We recruited participants from 3 urban, primary care and 1
      pulmonary practice from July to September 2015 in Hartford, CT. Forty-one
      participated in four focus groups, which included a demonstration of the
      technology. Participants were probed with open-ended questions on the type,
      frequency, and format of inter-visit patient information they found useful.
      RESULTS: 41 participants (mean age 49 (+/-13.7) years) were board-certified
      clinicians (41% MDs and 20% mid-level practitioners), practiced medicine on an
      average of 19 (+/-14) years, were primarily white (59%) and women (78%).
      Clinicians wanted 1) adherence to prescribed inhaler therapy and 2) data on
      inhaler technique. Clinicians wanted it at the time of a scheduled clinic visit
      but also wanted inter-visit alerts for excessive use of rescue therapy.
      Pulmonologists liked the mobile spirometer's provision of inter-visit lung
      function data; pediatricians did not share this view. Concerns with data accuracy
      were raised due to families who shared inhalers, access to smartphones, and
      protection of health information. CONCLUSIONS: Overall, clinicians view an asthma
      mobile health technology as enhancing the patient-centered medical home.
      Pediatric primary care clinicians and pulmonologists want different information
      from a mobile app.

PMID- 27880050
TI  - Stable State Proadrenomedullin Level in COPD Patients: A Validation Study.
AB  - In patients with stable COPD, proadrenomedullin (MR-proADM) has been shown to be
      a good predictor for mortality. This study aims to provide an external validation
      of earlier observed cut-off values used by Zuur-Telgen et al. and Stolz.et al. in
      COPD patients in stable state and at hospitalization for an acute exacerbation of
      COPD (AECOPD). From the COMIC cohort study we included 545 COPD patients with a
      blood sample obtained in stable state (n = 490) and/or at hospitalization for an
      AECOPD (n = 101). Time to death was compared between patients with MR-proADM cut
      off scores 0.71 and 0.75 nmol/L for stable state or 0.79 and 0.84 nmol/l for
      AECOPD. The predictive value of MR-proADM for survival was represented by the C
      statistic. Risk ratios were corrected for sex, age, BMI, presence of heart
      failure, and GOLD stage. Patients above the cut-off of 0.75 nmol/l had a 2-fold
      higher risk of dying than patient below this cut-off (95% CI: 1.20-3.41). The cut
      off of 0.71 nmol/l showed only a borderline significantly higher risk of 1.67
      (95% CI: 0.98-2.85). The corrected odds ratios for one-year mortality were 3.15
      (95% CI 1.15-8.64) and 3.70 (95% CI 1.18-11.6) in patients with MR-proADM levels
      above versus below the cut-off of respectively 0.75 and 0.71 nmol/l measured in
      stable state. MR-proADM levels in samples at hospitalization for an AECOPD were
      not predictive for mortality in this validation cohort. MR-proADM in stable state
      is a powerful predictor for mortality.

PMID- 27880051
TI  - Multimorbidities of asthma, allergies, and airway illnesses in childhood: Chance
      or not chance?
AB  - OBJECTIVES: We investigated patterns of multimorbidities among asthma, allergies,
      and respiratory illnesses in preschool children. We investigated multimorbidities
      of lifetime asthma, allergic rhinitis, eczema, food allergy, pneumonia, and ear
      infections; and multimorbidities of current (in the last year before the survey)
      wheeze, dry cough, rhinitis, eczema, and common cold during childhood. We further
      analyzed whether prevalences of these multimorbidities were due to chance.
      METHODS: A cross-sectional study was conducted in 72 kindergartens of Shanghai,
      China. Parents of preschool children were surveyed with a modified ISAAC
      questionnaire. Observed prevalences (OPs), expected prevalences (EPs), absolute
      excess comorbidities (AECs), and relative excess comorbidities (RECs) of various
      combinations of illnesses were calculated to indicate whether the combined
      illnesses were related. RESULTS: We analyzed questionnaires for children aged 4-6
      years, whose 13,335 questionnaires were the majority of the total 15,266 returned
      questionnaires (response rate: 85.3%). The studied illnesses were common. For
      children who had more than three lifetime or current illnesses, OPs tended to be
      higher than EPs. Most OPs and EPs were higher in boys than in girls, and were
      higher in children with a family history of atopy (FHA) than in children without
      FHA. AECs and RECs between boys and girls as well as between children with and
      without FHA were substantially different. CONCLUSIONS: Our findings suggest that
      multimorbidities among childhood asthma, allergies, and respiratory illnesses are
      likely not random, but rather share etiology. Specific patterns of childhood
      asthma multimorbidities perhaps differ between boys and girls and between
      children with and without FHA.

PMID- 27880052
TI  - Functional impact of different muscle localization techniques for Botulinum
      neurotoxin A injections in clinical routine management of post-stroke spasticity.
AB  - BACKGROUND: Treatment options for spasticity include intramuscular botulinum
      neurotoxin A (BoNT-A) injections. Both ultrasound (US) or electromyographic (EMG)
      guided BoNT-A injections are employed to isolate muscles. To date, most studies
      have included patients naive to BoNT-A or following a prolonged wash out phase.
      OBJECTIVE: To determine the impact of US/EMG guided BoNT-A injections on function
      in outpatients with spasticity receiving an established re-injection regime.
      METHODS: Thirty patients post-stroke were investigated in a single-blinded,
      randomized controlled trial using a cross-over design for the EMG and US and a
      parallel design for the control group. The Modified Ashworth (MAS), Disability
      Assessment (DAS), Quality of Life (EQ-5D), self-rating scale and Barthel Index
      were assessed pre- and post-BoNT-A injections of upper limb muscles by a to the
      injection technique blinded person. RESULTS: MAS improved in arm, finger and
      upper limb 4 weeks after BoNT-A treatment. The improvement showed no significant
      differences between the three injection techniques. Barthel Index, DAS and EQ-5D
      remained unchanged in all groups. CONCLUSIONS: This pilot study questions the
      impact of the instrumental guided injection techniques on everyday functionality
      in a routine clinical setting with established re-injection intervals. Larger
      trials are warranted with patients who are under long-term treatment on a regular
      basis.

PMID- 27880053
TI  - Disparities in emergency department visits in American children with asthma: 2006
      2010.
AB  - OBJECTIVE: This article was to examine the trends in emergency department (ED)
      visits for asthma among American children in 2006-2010 across sociodemographic
      factors, parental smoking status, and children's body weight status. METHODS: We
      analyzed 5,535 children aged 2-17 years with current asthma in the Asthma Call
      Back Survey in 2006-2010. Multivariate log binomial regression was used to
      examine the disparities of ED visits by demographics, socioeconomic status,
      parental smoking status, children's body weight status, and the level of asthma
      control. We controlled for average state-level air pollutants. Prevalence ratios
      (PRs) and 95% confidence intervals (CIs) were reported. RESULTS: Minority
      children with current asthma had higher risks of ED visits compared with white
      children in 2009 and 2010, e.g., the PR (95% CI) for black children in 2009 was
      3.64 (1.79, 7.41). Children who had current asthma and more highly educated
      parents experienced a higher risk of ED visits in 2007 (PRs [95% CI] = 2.15
      [1.02, 4.53] and 2.97 [1.29, 6.83] for children with some college or college
      graduated parents), but not significant in other years. Children with
      uncontrolled asthma were significantly more likely to visit the ED in 2008 (PRs
      [95% CI] = 2.79 [1.44, 5.41] and 6.96 [3.55, 13.64] for not-well-controlled and
      very poorly controlled children with asthma). CONCLUSIONS: Minority children with
      current asthma or children with uncontrolled asthma were more likely to visit EDs
      for asthma treatment. However, the disparities in ED visits across
      sociodemographics, health status, or asthma control vary in scale and
      significance across time. More research is needed to explain these differences.

PMID- 27880054
TI  - Elucidating the role of compression waves and impact duration for generating mild
      traumatic brain injury in rats.
AB  - BACKGROUND: In total, 3.8 million concussions occur each year in the US leading
      to acute functional deficits, but the underlying histopathologic changes that
      occur are relatively unknown. In order to improve understanding of acute injury
      mechanisms, appropriately designed pre-clinical models must be utilized. METHODS:
      The clinical relevance of compression wave injury models revolves around the
      ability to produce consistent histopathologic deficits. Mild traumatic brain
      injuries activate similar neuroinflammatory cascades, cell death markers and
      increases in amyloid precursor protein in both humans and rodents. Humans,
      however, infrequently succumb to mild traumatic brain injuries and, therefore,
      the intensity and magnitude of impacts must be inferred. Understanding
      compression wave properties and mechanical loading could help link the
      histopathologic deficits seen in rodents to what might be happening in human
      brains following concussions. RESULTS: While the concept of linking duration and
      intensity of impact to subsequent histopathologic deficits makes sense, numerical
      modelling of compression waves has not been performed in this context. In this
      interdisciplinary work, numerical simulations were performed to study the
      creation of compression waves in an experimental model. CONCLUSION: This work was
      conducted in conjunction with a repetitive compression wave injury paradigm in
      rats in order to better understand how the wave generation correlates with
      histopathologic deficits.

PMID- 27880055
TI  - Excessive daytime sleepiness in asthma: What are the risk factors?
AB  - OBJECTIVE: Previous studies have found that excessive daytime sleepiness (EDS) is
      a more common problem in asthmatic subjects than in the general population. The
      aim of this study was to investigate whether the prevalence of EDS is increased
      in asthmatic subjects and, if so, to analyse the occurrence of potential risk
      factors for EDS in asthmatics. METHODS: Cross-sectional epidemiological study. In
      2008, a postal questionnaire was sent out to a random sample of 45,000
      individuals aged 16-75 years in four Swedish cities. RESULTS: Of the 25,160
      persons who participated, 7.3% were defined as having asthma. The prevalence of
      EDS was significantly higher in asthmatic subjects (42.1% vs. 28.5%, p < 0.001)
      compared with non-asthmatic subjects. Asthma was an independent risk factor for
      EDS (adjusted OR 1.29) and the risk of having EDS increased with asthma severity.
      Risk factors for EDS in subjects with asthma included insomnia (OR, 3.87; 95% CI,
      3.10-4.84); chronic rhinosinusitis (OR, 2.00; 95% CI, 1.53-2.62); current smoking
      (OR, 1.60; 95% CI, 1.15-2.22) and obesity (OR, 1.53; 95% CI, 1.09-2.13).
      CONCLUSIONS: EDS is a common problem among subjects with asthma. Asthma is an
      independent risk factor for having EDS. Furthermore, subjects with asthma often
      have other risk factors for EDS, many of them potentially modifiable.

PMID- 27880057
TI  - Ankle plantarflexor spasticity is not differentially disabling for those who are
      weak following traumatic brain injury.
AB  - PRIMARY OBJECTIVES: The main aim of this study was to determine whether the
      presence of distal lower-limb spasticity had a greater impact on mobility for
      those who had greater levels of muscle paresis following traumatic brain injury
      (TBI). RESEARCH DESIGN: This was a cross-sectional cohort study of convenience.
      Seventy-five people attending physiotherapy for mobility limitations following
      TBI participated in this study. All participants had sustained a moderate-severe
      TBI and were grouped according to the presence or absence of ankle plantarflexor
      spasticity for comparison. MAIN OUTCOMES AND RESULTS: The primary outcome measure
      for mobility was self-selected walking speed and the primary outcome measure for
      muscle strength was hand-held dynamometry. Secondary outcome measures for
      mobility and muscle strength were the High-level Mobility Assessment Tool (HiMAT)
      and ankle power generation (APG) at push-off. Spasticity was quantified with the
      Modified Tardieu scale. Participants with ankle plantarflexor spasticity (Group
      2) had slower self-selected walking speeds. There was no statistically
      significant effect for Group and plantarflexor strength (p = 0.81). CONCLUSION:
      Although participants with ankle plantarflexor spasticity walked significantly
      slower than those without, the presence of ankle plantarflexor spasticity did not
      lead to greater mobility limitations for those who were weak.

PMID- 27880056
TI  - Bronchial biopsy and reactivity in patients with chest tightness relieved with
      bronchodilator.
AB  - OBJECTIVE: It has been hypothesized that some patients with chest tightness of
      unknown origin can be successfully treated with a bronchodilator and that they
      should be diagnosed with chest pain variant asthma. We conducted a prospective
      study to characterize newly diagnosed patients with chest tightness relieved with
      bronchodilator use and without characteristic bronchial asthma attacks. METHODS:
      Eleven patients were registered following recurrent positive responses of chest
      tightness to inhalation of a beta2-agonist. These patients underwent assessments
      of airway responsiveness to methacholine, bronchial biopsy and bronchial lavage
      under fiber-optic bronchoscopy before receiving treatment. RESULTS: For the
      patients with chest tightness relieved with bronchodilator use, the bronchial
      biopsy specimens exhibited significant increases in lymphocyte and macrophage
      infiltration (p < 0.05) and no significant increase in eosinophils (p = 0.2918)
      compared with the control subjects. The bronchial responsiveness to methacholine
      was increased in two of the patients with chest tightness, and it was not
      increased in seven; in addition, increased percentages of eosinophils were
      detected in bronchial lavage fluid (5% or more) from two patients, but no
      increase was detected in eight patients. CONCLUSIONS: We suspect that the chest
      tightness was induced by airway constriction in these patients, but further study
      is necessary to validate this hypothesis. We propose that the chest tightness
      relieved with bronchodilator use was attributed to airway constriction resulting
      from inflammation with lymphocytes and macrophages and/or that the chest
      tightness was directly attributed to airway inflammation. This clinical trial is
      registered at www.umin.ac.jp (UMIN13994 and UMIN 16741).

PMID- 27880058
TI  - Fish-Oil-Derived DHA-mediated Enhancement of Apoptosis in Acute Lymphoblastic
      Leukemia Cells is Associated with Accumulation of p53, Downregulation of
      Survivin, and Caspase-3 Activation.
AB  - In acute lymphoblastic leukemia (ALL), resistance to chemotherapy is associated
      with inactivation of p53 and upregulation of survivin. Thus, targeting the p53
      and survivin expression may provide an attractive strategy for ALL treatment. It
      has been shown that fish-oil-derived docosahexaenoic acid (DHA) activates several
      antitumorigenic mechanisms in tumor cells, but little is known regarding the role
      of DHA on modulating p53 and survivin expression in ALL cells. In this study, we
      investigated the alterations of the p53 and survivin expression and induction of
      apoptosis in DHA-treated Molt-4 cells that serve as a model for ALL cells. Molt-4
      cells were treated with 50, 100, 150, and 200 MUM DHA after which cell
      proliferation, survivin mRNA and protein levels, p53 protein level, caspase-3
      activation, and apoptotic rates were evaluated by different cellular and
      molecular techniques. After 48- and 72-h treatments with DHA at concentrations
      ranging from 50 to 200 MUM, cell proliferation rates were measured to be 80.5
      44.4%, and 73.4-14.4%, respectively, compared to untreated cells. We also found
      that treatment for 48 h with 200 MUM DHA resulted in 10.8- and 3.6-fold increase
      in p53 protein level and caspase-3 activation followed by 4.7-and 1.6-fold
      decrease in survivin mRNA and protein levels, respectively, compared to untreated
      cells. Treatment of cells with different concentrations of DHA dramatically
      increased the p53/survivin and caspase-3/survivin ratios by 2.8- to 16.9-fold and
      3.3 to 5.6-fold increases, respectively, compared to untreated cells. A decrease
      in the number of cells ranging from 16% to 70% and an increase in the number of
      apoptotic cells ranging from 9.3% to 93% was also observed with increasing DHA
      concentrations. In conclusion, p53 and survivin may provide promising targets of
      DHA in ALL cells and this compound with high proapoptotic capacity represents the
      possibility of its therapeutic application for ALL treatment.

PMID- 27880059
TI  - Repetition-lag memory training is feasible in patients with chronic stroke,
      including those with memory problems.
AB  - PRIMARY OBJECTIVE: Repetition-lag memory training was developed to increase
      individuals' use of recollection as opposed to familiarity in recognition memory.
      The goals of this study were to examine the feasibility of repetition-lag
      training in patients with chronic stroke and to explore whether the training
      might show suggestions of transfer to non-trained tasks. RESEARCH DESIGN: Quasi
      experimental. METHODS AND PROCEDURES: Patients (n = 17) took part in six
      repetition-lag training sessions and their gains on the training and non-trained
      tasks were compared to those of age-matched healthy controls (n = 30). MAIN
      OUTCOMES AND RESULTS: All but two patients completed the training, indicating
      that the method is feasible with a wide range of patients with stroke. The amount
      patients gained on the training task was similar to that of healthy controls
      (that is, the Group * Time interactions were by-and-large not significant),
      suggesting that patients with stroke might benefit to the same degree as healthy
      adults from this training. Both groups showed some indication of transfer to the
      non-trained backward digit span task and visuospatial memory. CONCLUSIONS: These
      findings show that repetition-lag memory training is a possible approach with
      patients with stroke to enhance recollection. Further research on the method's
      efficacy and effectiveness is warranted.

PMID- 27880060
TI  - Neurogenic pulmonary oedema complicating traumatic posterior fossa extradural
      haematoma: Case report and review.
AB  - INTRODUCTION: Pulmonary oedema is accumulation of fluid in the lung air spaces
      and interstitia. Neurogenic pulmonary oedema (NPE) is a potentially life
      threatening condition which has been noted in head injury, subarachnoid
      haemorrhage (SAH), intracerebral haemorrhage (ICH) and others. Timely management
      is crucial to achieve good outcome; however, no specific guidelines have been
      defined. METHODS: A 33-year female involved in a motor vehicular accident had a
      GCS of 14/15 and CT scan showed a moderate-sized unilateral posterior fossa
      extradural haematoma (PFEDH). She had sudden deterioration in her haemodynamic
      status with drop in sensorium 2 hours after admission. There was a copious amount
      of frothy secretions noted on intubation and she was diagnosed as having NPE.
      RESULTS: Sub-occiptial craneictomy (SOC) with haematoma evacuation was performed
      and was managed with PEEP mechanical ventilation post-operatively. Excellent
      outcome was obtained and was discharged with a GOS of 5. CONCLUSIONS: NPE is a
      poorly understood and uncommon complication of acute CNS injury and should be
      considered in any patient with acute respiratory distress in the setting of CNS
      injury. Reduction in ICP and supportive mechanical ventilation form the mainstay
      of management. Diagnosis of NPE remains challenging and more reliable diagnostic
      criteria need to be defined to identify such cases with greater frequency.

PMID- 27880061
TI  - The safety profile of monoclonal antibodies for chronic lymphocytic leukemia.
AB  - INTRODUCTION: Monoclonal antibodies (MoAbs), non-chemotherapeutic agents
      targeting the antigens present on chronic lymphocytic leukemia (CLL) lymphocytes,
      are being implemented increasingly more often as treatment options. Areas
      covered: This article reviews the similarities and differences in the structure,
      mechanism of action, efficacy and safety profile of commercially-available MoAbs
      and prevents new agents potentially useful for CLL treatment. Publications in
      English before June 2016 were surveyed on the MEDLINE database for articles.
      Proceedings of the American Society of Hematology held during the last five years
      were also included. Expert opinion: MoAbs, especially those targeting CD20, are
      highly effective biological options for first-line and salvage treatment of CLL,
      particularly in chemoimmunotherapy, and possibly also as maintenance therapy.
      Treatment with MoAbs is associated with reduced risk of such adverse events as
      cytopenias, infections and secondary neoplasias and is generally well tolerated.
      Depending on antibody type, the most common adverse events are usually transient
      and limited to grade 1 and 2 infusion-related reactions. In addition to
      commercially available MoAbs, several other antibodies exist which are targeted
      against different antigens studied in the clinical trials.

PMID- 27880062
TI  - The effect of vegetarian diets on iron status in adults: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Vegetarian diets exclude meat, seafood, and products containing these
      foods. Although the vegetarian lifestyle could lead to a better health status in
      adults, it may also bear risks for certain nutritional deficiencies. Cross
      sectional studies and narrative reviews have shown that the iron status of
      vegetarians is compromised by the absence of highly bioavailable haem-iron in
      meatless diets and the inhibiting effect of certain components present in plant
      foods on non-haem iron bioavailability. METHODS: The databases Pubmed, Scopus,
      Embase, and Cochrane CentralRegister of Controlled Trials were searched for
      studies comparing serum ferritin, as the major laboratory parameter for iron
      status of adult vegetarians with non-vegetarian control groups. A qualitative
      review was conducted as well as an inverse-variance random-effects meta-analysis
      to pool available data. In addition the effect of vegetarian diets according to
      gender was investigated with a subgroup analysis. The results were validated
      using a sensitivity analysis. RESULTS: A total of 27 cross-sectional studies and
      three interventional studies were selected for the systematic review. The meta
      analysis which combined data of 24 cross-sectional studies showed that adult
      vegetarians have significantly lower serum ferritin levels than their non
      vegetarian controls (-29.71 ug/L, 95% CI [-39.69, -19.73], p < 0.01). Inclusion
      of semi-vegetarian diets did not change the results considerably (-23.27 ug/L,
      95% CI [-29.77, -16.76], p < 0.01). The effects were more pronounced in men (
      61.88 ug/L, 95% CI [-85.59, -38.17], p < 0.01) than in both premenopausal women (
      17.70 MUg/L, 95% CI [-29.80, -5.60], p < 0.01) and all women (-13.50 MUg/L, 95%
      CI [-22.96, -4.04], p < 0.01), respectively. CONCLUSIONS: In conclusion our
      results showed that vegetarians are more likely to have lower iron stores
      compared with non-vegetarians. However, since high iron stores are also a risk
      factor for certain non-communicable diseases, such as type 2 diabetes, it is
      recommended that not only vegetarians but also non-vegetarians should regularly
      control their iron status and improve their diet regarding the content and
      bioavailability of iron by consuming more plants and less meat.

PMID- 27880063
TI  - Interactions between phytochemicals from fruits and vegetables: Effects on
      bioactivities and bioavailability.
AB  - The combinations of two or more phytochemicals bring about changes in the
      ultimate biological effects and/or the bioavailability of each component. A
      number of mixtures of pure bioactive compounds or phytochemical-containing plant
      extracts provide synergy with regard to antioxidant status, anti-inflammation,
      anti-cancer and chemoprevention of several oxidative stress and metabolic
      disorders in vitro. The biological activities of food phytochemicals depend upon
      their bioaccessibility and bioavailability which can be affected by the presence
      of other food components including other bioactive constituents. The interactions
      between phytochemicals during intestinal absorption could result in changes in
      the bioavailability of the compounds, which in turn affects the intensity of
      their bioactivities. This paper provides an overview of combined biological
      effects of phytochemical mixtures derived from fruits and vegetables with a focus
      on anti-oxidative, anti-inflammatory and anti-carcinogenic activities. The
      bioavailability impairment or enhancement caused by the co-consumption of dietary
      phytochemicals is also discussed. Finally, research gaps for future studies on
      phytochemical interactions are identified.

PMID- 27880064
TI  - A randomised controlled feasibility trial of Group Cognitive Behavioural Therapy
      for people with severe asthma.
AB  - OBJECTIVES: Evidence for the efficacy of Cognitive Behavioural Therapy (CBT) in
      asthma is developing but it is not known if this translates to benefits in severe
      asthma or if a group approach is acceptable to this patient group. This study
      aimed to assess the feasibility and acceptability of Group-CBT in severe asthma.
      METHOD: This was a two-centre, randomised controlled parallel group feasibility
      study. Eligible participants (patients with severe asthma and a clinically
      significant diagnosis of anxiety and/or depression - Hospital Anxiety and
      Depression Scale (HAD) score greater than 8 for the anxiety or depression sub
      scale) received Group-CBT in weekly sessions for eight consecutive weeks and
      usual care or usual care only. Follow-up was for 16 weeks and end points were:
      Asthma Quality of Life Questionnaire, Asthma Control Questionnaire, HAD, Dyspnoea
      12, EuroQual-5D and EuroQuol-VAS. RESULTS: 51 patients were randomised: 36% (51
      out of 140) consent rate and attrition at week 16 was 12. Screening logs
      indicated that study take-up was influenced by patients living long distances
      from the treatment centre and inability to commit to the weekly demands of the
      programme. Drop-out was higher in Group-CBT compared due to inability to commit
      to the weekly programme because of poor health. Participants who contributed to
      focus group discussions reported that Group-CBT contributed to a better
      understanding of their illness and related approaches to anxiety management and
      acceptance of their asthma condition. Although weekly face-to-face sessions were
      challenging, this was the preferred method of delivery for these participants.
      CONCLUSIONS: This feasibility study shows that Group-CBT warrants further
      investigation as a potentially promising treatment option for patients with
      severe asthma. It has been possible but not easy to recruit and retain the
      sample. Options for a less demanding intervention schedule, such as less frequent
      face-to-face visits and the use of web-based interventions, require careful
      consideration.

PMID- 27880065
TI  - Fluctuations in the emotional intelligence of therapy students during clinical
      placements: Implication for educators, supervisors, and students.
AB  - This study investigated the changes in emotional intelligence (EI) of
      occupational therapy, physiotherapy, and speech pathology students (therapy
      students). Clinical placements have multiple benefits including the development
      of interprofessional skills, enhancing practice skills and interpersonal skills.
      Higher EI competencies have been shown to have a positive impact on patient
      outcomes, teamwork skills, dealing with stress, and patient satisfaction. Data
      for this study were collected at two time points: before third-year therapy
      students commenced extended clinical placements (T1 with 261 students) and
      approximately 7 months later after students had completed one or more clinical
      placements (T2 with 109 students). EI was measured using the Emotional Quotient
      Inventory 2.0 (EQ-i2.0). Only one EI score, assertiveness, demonstrated a
      significant decline. No EI score showed a significant increase. A third or more
      of the students showed increases of five points or more in self-actualisation,
      emotional expression, independence, reality testing and optimism. However, of
      concern were the five EI scores where therapy students' EI scores decreased by
      more than five points: assertiveness (where 38% of students declined), problem
      solving (37%), impulse control (35%), self-actualisation (35%), and stress
      tolerance (33%). With EI scores declining for some students during clinical
      placements, there are implications for clinical supervisors and interprofessional
      facilitators as clinical performance may decline concurrently. There is a range
      of potential reasons that clinical placements could negatively influence the EI
      competencies of a therapy student, including poor clinical supervision, conflict
      between a student, and supervisor and failing a clinical placement. The research
      suggests that interprofessional facilitators and university educators might
      consider students undertaking EI tests before clinical placements.

PMID- 27880066
TI  - Features of KAT6B-related disorders in a patient with 10q22.1q22.3 deletion.
AB  - BACKGROUND: Blepharophimosis is a fixed reduction in the vertical distance
      between the upper and lower eyelids with short palpebral fissures. It is a rare
      facial malformation and is considered an important diagnostic feature in
      dysmorphic analysis. It is likely that many patients with blepharophimosis-mental
      retardation syndrome have submicroscopic chromosomal rearrangements, and the use
      of molecular karyotyping can narrow the known blepharophimosis-mental retardation
      critical regions or clarify the effect of the haploinsufficiency of the involved
      genes on the phenotype. MATERIALS AND METHODS: A female patient presented with
      bilateral blepharophimosis, ptosis, epicanthus inversus, telecanthus, low-set and
      small ears, other minor anomalies, hypotonia and psychomotor developmental delay.
      Metabolic investigations and array CGH analysis were performed. The results of
      molecular karyotyping were confirmed by real-time PCR analysis. RESULTS:
      Molecular karyotyping revealed a 5.2 Mb deletion in the 10q22.1q22.3 region. Real
      time PCR analysis of the proband and her parents confirmed the deletion in the
      proband and revealed its de novo origin. CONCLUSIONS: With ptosis, hypotonia, and
      developmental delay as the main diagnostic features of our patient, the effect of
      histone acetyltransferase-encoding KAT6B gene haploinsufficiency was suspected to
      have a significant role in determining the phenotype. Detailed clinical
      characterization of the patient provided additional information on the clinical
      manifestation of the 10q22 deletion.

PMID- 27880067
TI  - Cell proliferation downregulated by TGF-beta2-triggered G1/S checkpoint in
      clinical CAFs.
AB  - The metabolic reprogramming is indispensible for the fast growth of tumor cells.
      The metabolism of CAFs is reprogrammed to aerobic glycolysis too. However, it is
      not clear whether this metabolic reprogramming promotes the growth of CAFs
      themselves. In this study, we found that the proliferation rate of CAFs was
      slower than NAFs, which was determined by cell counting, BrdU assay and flow
      cytometry analysis. Moreover, we found TGF-beta signaling regulated cell growth
      of CAF through RNA-sequencing analysis and Western blot, which was further
      supported by the observation that TGF-beta2 was highly expressed in colon cancer
      tissues. In the end, we demonstrated that CAFs were critical to tumor cell
      proliferation, which was supported by the evidence of their close localization in
      clinical tumor tissue and tumor promoting effect in mice. In brief, our data have
      manifested that the proliferation rate is decreased in CAFs, which enable CAFs
      generate more intermediate metabolites to support tumor cells growth, suggesting
      CAFs is an ideal target for tumor therapy.

PMID- 27880068
TI  - Human hair-follicle associated pluripotent (hHAP) stem cells differentiate to
      cardiac-muscle cells.
AB  - We have previously demonstrated that nestin-expressing hair follicle-associated
      pluripotent (HAP) stem cells are located in the bulge area. HAP stem cells have
      been previously shown to differentiate to neurons, glial cells, keratinocytes,
      smooth-muscle cells, melanocytes and cardiac-muscle cells in vitro. Subsequently,
      we demonstrated that HAP stem cells could effect nerve and spinal cord
      regeneration in mouse models, differentiating to Schwann cells and neurons. In
      previous studies, we established an efficient protocol for the differentiation of
      cardiac-muscle cells from mouse HAP stem cells. In the present study, we isolated
      the upper part of human hair follicles containing human HAP (hHAP) stem cells.
      The upper parts of human hair follicles were suspended in DMEM containing 10% FBS
      where they differentiated to cardiac-muscle cells as well as neurons, glial
      cells, keratinocytes and smooth-muscle cells. This method is appropriate for
      future use with human hair follicles to produce hHAP stem cells in sufficient
      quantities for future heart, nerve and spinal cord regeneration in the clinic.

PMID- 27880069
TI  - Role of First-Trimester HbA1c as a Predictor of Adverse Obstetric Outcomes in a
      Multiethnic Cohort.
AB  - Context: Risk of obstetric complications increases linearly with rising maternal
      glycemia. Testing hemoglobin A1c (HbA1c) is an effective option to detect
      hyperglycemia, but its association with adverse pregnancy outcomes remains
      unclear. Emerging data sustain that an early HbA1c >=5.9% could act as a
      pregnancy risk marker. Objective: To determine, in a multiethnic cohort, whether
      an early >=5.9% HbA1c could be useful to identify women without diabetes mellitus
      at increased pregnancy risk. Design and Setting: A prospective study was
      conducted at Hospital del Mar, Barcelona, between April 2013 and September 2015.
      Patients and Intervention: A total of 1631 pregnant women had an HbA1c
      measurement added to their first antenatal blood tests and were screened for
      gestational diabetes mellitus at 24 to 28 weeks' gestation. Outcome Measures:
      Primary outcome was macrosomia. Secondary outcomes were preeclampsia, preterm
      birth, and cesarean section rate. Results: A total of 1228 pregnancies were
      included for outcome analysis. Women with HbA1c >=5.9% (n = 48) showed a higher
      rate of macrosomia (16.7% vs 5.9%, P = 0.008) and a tendency toward a higher rate
      of preeclampsia (9.32% vs 3.9%, P = 0.092). There were no statistically
      significant differences in other pregnancy outcomes. After adjusting for
      potential confounders, an HbA1c >=5.9% was independently associated with a 3-fold
      increased risk of macrosomia (95% confidence interval, 1.127 to 8.603, P = 0.028)
      and preeclampsia (95% confidence interval, 1.086 to 11.532, P = 0.036).
      Conclusions: In a multiethnic population, an early HbA1c >=5.9% measurement
      identifies women at high risk for poorer pregnancy outcomes independently of
      gestational diabetes mellitus diagnosis later in pregnancy. Further studies are
      required to establish cutoff points adapted to each ethnic group and to assess
      whether early detection and treatment are of benefit.

PMID- 27880070
TI  - Influence of Premature Mortality on the Link Between Type 2 Diabetes and Hip
      Fracture: The Fremantle Diabetes Study.
AB  - Context: Studies of hip fracture complicating diabetes have not considered the
      effect of premature mortality. Objective: The aim of our study was to determine
      influence of the competing risk of death on the association between type 2
      diabetes and hip fracture. Design: The study was designed as a longitudinal
      observational study. Setting: The study setting was an urban community. Patients:
      Participants included 1291 patients with type 2 diabetes (mean age 64.0 years)
      and 5159 matched residents without diabetes. Main Outcome Measures: Primary
      outcome measures were incident hip fracture hospitalizations and deaths. Hip
      fracture risk was assessed using proportional hazards and competing risk
      regression modeling. Results: During a mean of 14.1 years of follow-up, the
      incidence rate ratio for first hip fracture hospitalization in participants with
      vs without diabetes was 1.33 [95% confidence interval (CI), 1.05 to 1.68; P =
      0.013]. Type 2 diabetes was associated with a cause-specific hazard ratio (csHR)
      for hip fracture of 1.50 (95% CI, 1.19 to 1.89; P < 0.001) and a subdistribution
      hazard ratio (sdHR) of 1.21 (95% CI, 0.96 to 1.52; P = 0.11) after adjustment for
      age, sex, and comorbidities. In patients with diabetes, significant csHRs for
      incident hip fracture were male sex (protective), body mass index (protective),
      insulin use, and renal impairment. These variables, with increasing age, also had
      significant sdHRs. Conclusions: The diabetes-associated risk of hip fracture is
      attenuated after allowing for the competing risk of death. Risk factors for hip
      fracture in diabetes were those in reported in general population studies plus
      insulin use.

PMID- 27880071
TI  - Interplay of cis- and trans-regulatory mechanisms in the spliceosomal RNA
      helicase Brr2.
AB  - RNA helicase Brr2 is implicated in multiple phases of pre-mRNA splicing and thus
      requires tight regulation. Brr2 can be auto-inhibited via a large N-terminal
      region folding back onto its helicase core and auto-activated by a catalytically
      inactive C-terminal helicase cassette. Furthermore, it can be regulated in trans
      by the Jab1 domain of the Prp8 protein, which can inhibit Brr2 by intermittently
      inserting a C-terminal tail in the enzyme's RNA-binding tunnel or activate the
      helicase after removal of this tail. Presently it is unclear, whether these
      regulatory mechanisms functionally interact and to which extent they are
      evolutionarily conserved. Here, we report crystal structures of Saccharomyces
      cerevisiae and Chaetomium thermophilum Brr2-Jab1 complexes, demonstrating that
      Jab1-based inhibition of Brr2 presumably takes effect in all eukaryotes but is
      implemented via organism-specific molecular contacts. Moreover, the structures
      show that Brr2 auto-inhibition can act in concert with Jab1-mediated inhibition,
      and suggest that the N-terminal region influences how the Jab1 C-terminal tail
      interacts at the RNA-binding tunnel. Systematic RNA binding and unwinding studies
      revealed that the N-terminal region and the Jab1 C-terminal tail specifically
      interfere with accommodation of double-stranded and single-stranded regions of an
      RNA substrate, respectively, mutually reinforcing each other. Additionally, such
      analyses show that regulation based on the N-terminal region requires the
      presence of the inactive C-terminal helicase cassette. Together, our results
      outline an intricate system of regulatory mechanisms, which control Brr2
      activities during snRNP assembly and splicing.

PMID- 27880073
TI  - An interprofessional health assessment program in rural amateur sport.
AB  - Effective interprofessional learning (IPL) in multisectoral collaborations such
      as those linking health services within communities can provide an authentic
      experience for students and also appears to be the most effective way to achieve
      health changes in targeted population groups. The aim of this study was to
      facilitate the IPL of students at a rural university in a multisectoral health
      assessment programme and to promote health in players of rural amateur sport. Two
      rural rugby league teams took part in three pre-season health assessments
      conducted by general medical practitioners, practice nurses, and nursing,
      osteopathy, and exercise science students. The Readiness for Interprofessional
      Learning Scale questionnaire and a series of focus groups were used to evaluate
      participants' experiences of the programme. Results indicated that students saw
      the benefits for patients and 93% valued the opportunity to improve
      interprofessional communication, problem-solving and team skills. Some students
      felt they needed to learn more about their own professional role before learning
      about others, and instances of stereotyping were identified. The programme also
      enabled early detection of potential health risks and referral for medical care,
      management of musculoskeletal conditions, and health promotion. These health
      assessments would be readily transferred to other multisectoral sporting
      settings.

PMID- 27880072
TI  - Oncogenic KRAS and the EGFR loop in pancreatic carcinogenesis-A connection to
      licensing nodes.
AB  - EGFR signaling has a critical role in oncogenic KRAS-driven tumorigenesis of the
      pancreas, whereas it is dispensable in other organs. The complex signaling
      network engaged by oncogenic KRAS and its modulation by EGFR signaling, remains
      incompletely understood. In order to study early signaling events activated by
      oncogenic KRAS in the pancreas, we recently developed a novel model system based
      on murine primary pancreatic epithelial cells enabling the time-specific
      expression of mutant KrasG12D from its endogenous promoter. Here, we discuss our
      findings of a KrasG12D-induced autocrine EGFR loop, how this loop is integrated
      by the MYC oncogene, and point to possible translational implications.

PMID- 27880075
TI  - Holes in the Head: The Art and Archeology of Trepanation in Ancient Peru, by John
      W. Verano.

PMID- 27880074
TI  - What does the fruitless gene tell us about nature vs. nurture in the sex life of
      Drosophila?
AB  - The fruitless (fru) gene in Drosophila has been proposed to play a master
      regulator role in the formation of neural circuitries for male courtship
      behavior, which is typically considered to be an innate behavior composed of a
      fixed action pattern as generated by the central pattern generator. However,
      recent studies have shed light on experience-dependent changes and sensory-input
      guided plasticity in courtship behavior. For example, enhanced male-male
      courtship, a fru mutant "hallmark," disappears when fru-mutant males are raised
      in isolation. The fact that neural fru expression is induced by neural activities
      in the adult invites the supposition that Fru as a chromatin regulator mediates
      experience-dependent epigenetic modification, which underlies the neural and
      behavioral plasticity.

PMID- 27880077
TI  - Teriparatide Treatment in Elderly Patients With Sacral Insufficiency Fracture.
AB  - Context and Objective: Pain-related immobility because of insufficiency fractures
      may result in serious complications and a high mortality rate in senile patients
      with preexisting comorbidities. This study aimed to evaluate the efficacy of
      teriparatide in patients with sacral insufficiency fractures. Design, Setting,
      and Participants: This retrospective, case-controlled, single center study,
      performed from 2009 to 2014, included 41 patients who underwent radiographs,
      magnetic resonance imaging, and/or bone scans to document sacral insufficiency
      fractures. Intervention: The intervention involved teriparatide at a once-daily
      subcutaneous dose of 20 MUg within 2 days of hospital admission (21 patients).
      Twenty patients (control group) did not receive teriparatide. Main Outcome
      Measures: Functional outcome was assessed using a visual analog scale for pain
      and the time to mobilization. Pelvic anteroposterior radiographs were repeated at
      0, 1, 4, 8, 12, and 16 weeks until radiographic evidence of cortical bridging at
      the fracture site was confirmed. Results: From the date of admission to 4 weeks,
      the mean visual analog scale score improved between the 2 groups. The mean time
      to mobilization was 1.2 +/- 0.4 weeks in patients who received teriparatide
      treatment, compared with 2.0 +/- 0.3 weeks in controls (P < 0.001). At 8 weeks,
      all fractures in the teriparatide treatment group and 4 fractures in the control
      group had healed. Conclusions: In senile patients with preexisting comorbidities
      who have sacral insufficiency fractures, teriparatide treatment may achieve
      earlier pain reduction and mobilization and reduce healing time.

PMID- 27880076
TI  - Correlation of ultra-widefield fundus autofluorescence patterns with the
      underlying genotype in retinal dystrophies and retinitis pigmentosa.
AB  - PURPOSE: Ultra-widefield fundus autofluorescence (UW-FAF) allows the
      characterization of the peripheral retinal features of vitreoretinal diseases.
      The purpose of this study was to examine possible genotypic/phenotypic
      correlations of UW-FAF patterns in patients with a variety of retinal dystrophies
      and retinitis pigmentosa (RP). METHODS: An IRB-approved retrospective consecutive
      case series study was performed of genetically characterized retinal dystrophy or
      RP patients who underwent UW-FAF imaging. UW-FAF was performed with the Optos
      200Tx system. Clinical variables, genotypic analysis, and phenotypic
      characteristics were reviewed. RESULTS: Seventeen patients were identified who
      had identified mutations in retinal dystrophy or RP genes and who also had
      undergone UW-FAF. Three patients had X-linked RP with RPGR mutations. Six
      patients had autosomal dominant RP (four with RHO mutations and one with a PRPF31
      mutation, and one with RDS/PRPH2 mutation). Four patients had autosomal recessive
      RP (four with USH2A mutations). Three patients had Leber Congenital Amaurosis
      (LCA) with mutations including CRB1, CEP290, and RPGRIP1. Macular
      hyperautofluorescence was noted in all patients. A ring of hyperautofluorescence
      was clear in patients with RHO and USH2A mutations, and patients with USH2A
      mutations demonstrated a second ring of hyperautofluorescence. In the periphery,
      patients with RHO or RPGR mutations exhibited hyperautofluorescence with patchy
      areas of hypoautofluorescence. Patients with USH2A mutations had a distinctive
      pattern of diffuse and homogeneous peripheral hypoautofluorescence. CONCLUSION:
      UW-FAF may provide important information to facilitate diagnosis and further
      research is needed to better characterize this technology as an imaging biomarker
      for genotype association in retinal dystrophies and RP.

PMID- 27880078
TI  - Serine racemase is expressed in islets and contributes to the regulation of
      glucose homeostasis.
AB  - NMDA receptors (NMDARs) have recently been discovered as functional regulators of
      pancreatic beta-cell insulin secretion. While these excitatory receptor channels
      have been extensively studied in the brain for their role in synaptic plasticity
      and development, little is known about how they work in beta-cells. In neuronal
      cells, NMDAR activation requires the simultaneous binding of glutamate and a rate
      limiting co-agonist, such as D-serine. D-serine levels and availability in most
      of the brain rely on endogenous synthesis by the enzyme serine racemase (Srr).
      Srr transcripts have been reported in human and mouse islets but it is not clear
      whether Srr is functionally expressed in beta-cells or what its role in the
      pancreas might be. In this investigation, we reveal that Srr protein is highly
      expressed in primary human and mouse beta-cells. Mice with whole body deletion of
      Srr (Srr KO) show improved glucose tolerance through enhanced insulin secretory
      capacity, possibly through Srr-mediated alterations in islet NMDAR expression and
      function. We observed elevated insulin sensitivity in some animals, suggesting
      Srr metabolic regulation in other peripheral organs as well. Srr expression in
      neonatal and embryonic islets, and adult deficits in Srr KO pancreas weight and
      islet insulin content, point toward a potential role for Srr in pancreatic
      development. These data reveal the first evidence that Srr may regulate glucose
      homeostasis in peripheral tissues and provide circumstantial evidence that D
      serine may be an endogenous islet NMDAR co-agonist in beta-cells.

PMID- 27880080
TI  - Anchoring interprofessional education in undergraduate curricula: The Heidelberg
      story.
AB  - The ability of health professionals to collaborate effectively has significant
      potential impact on patient safety and quality-care outcomes, especially given
      the increasingly complex and dynamic clinical practice environments of today.
      Educators of the health professions are faced with an immediate challenge to
      adapt curricula and traditional teaching methods to ensure graduates are equipped
      with the necessary interprofessional competencies and (inter)professional values
      for their future practice. The World Health Organization's "Framework for action
      in interprofessional education (IPE) and collaborative practice" promotes IPE as
      a key strategy to enhance patient outcomes by preparing a "collaborative practice
      ready health workforce." Logistical and attitudinal barriers can hinder
      integration of IPE into curricula. Lessons learned through the implementation of
      a planned change to establish four interprofessional seminars (team
      communication, medical error communication, healthcare English, and small
      business management) at Heidelberg University Medical Faculty, Germany, are
      described. A key factor in successfully anchoring IPE seminars in the
      undergraduate curricula was the structured approach drawing on change management
      concepts.

PMID- 27880079
TI  - Relationship Between Gastric Emptying and Diurnal Glycemic Control in Type 1
      Diabetes Mellitus: A Randomized Trial.
AB  - Context: In type 1 diabetes (T1D), delayed gastric emptying (GE) may predispose
      to a mismatch between insulin delivery and glucose absorption. Previous studies
      evaluated, only partly, the relationship between delayed GE and postprandial, but
      not diurnal, glycemia. Objective: To assess the relationship between GE
      disturbances and glycemic control in T1D and the effects of accelerating GE on
      glycemic control. Design, Setting, and Participants: This was a randomized
      placebo-controlled trial in 30 patients with T1D on an insulin pump at an
      academic medical center. Intervention(s): GE was evaluated with a [13C]-Spirulina
      breath test at baseline (GEbaseline), during intravenous saline or erythromycin
      (2 or 3 mg/kg; GEiv), and after 7 days of oral erythromycin or placebo (GEoral).
      Weighed meals were provided throughout the study. Main Outcome Measure(s): These
      were GE and continuous glucose monitoring (CGM). Results: The baseline
      glycosylated hemoglobin was 7.6% +/- 0.8% (60 +/- 8.7 mmol/mol); 12 patients
      (40%) had delayed GE; faster GE was associated with a greater postprandial CGM
      based glucose, but slower GE was not associated with postprandial hypoglycemia
      (<70 mg/dL). Intravenous (3 mg/kg) but not oral erythromycin accelerated GE. The
      relationship between GE and glycemia differed between the postprandial periods
      and the entire day. After adjusting for carbohydrate intake and insulin
      consumption, faster GE was associated with more hyperglycemia during the
      postprandial period but lower glucose values across the entire study.
      Conclusions: In T1D, pharmacologically mediated acceleration of GE increases
      postprandial CGM-based glucose. In contrast, delayed GE is associated with
      greater CGM-based glucose values over the entire day.

PMID- 27880082
TI  - Perceived performance and impact of a non-physician-led interprofessional team in
      a trauma clinic setting.
AB  - Faced with the challenge of meeting the wide degree of post-discharge needs in
      their trauma population, the University of Pittsburgh Medical Center (UPMC)
      developed a non-physician-led interprofessional team to provide follow-up care at
      its UPMC Falk Trauma Clinic. We assessed this model of care using a survey to
      gauge team member perceptions of this model, and used clinic visit documentation
      to apply a novel approach to assessing how this model improves the care received
      by clinic patients. The high level of perceived team performance and cohesion
      suggests that this model has been successful thus far from a provider
      perspective. Patients are seen most frequently by audiologists, while
      approximately half of physical therapy and speech language therapy consults
      generate a new therapy referral, which is interpreted as a potential change in
      the patient's care trajectory. The broader message of this analysis is that a
      collaborative, non-hierarchical team model incorporating rehabilitative
      specialists, who often operate independently of one another, can be successful in
      this setting, where patients appear to have a strong and previously under
      attended need for rehabilitative intervention.

PMID- 27880081
TI  - An emerging role for IQGAP1 in tight junction control.
AB  - IQGAP1 is a scaffold protein involved in the assembly of adherens junctions. Our
      work has recently revealed a novel role for IQGAP1 in the regulation of tight
      junctions (TJ) through differential recruitment of claudins to the nascent TJ.
      Here, we discuss the potential mechanisms of this regulation, including IQGAP1
      effects on CDC42, and IQGAP1 interactions with sorting/trafficking molecules
      (e.g. Exo70). Given the many roles of IQGAP1 and the large number of interacting
      partners, we focus our discussion of these functions in the context of junction
      formation, trafficking, growth factor signaling and cancer. We also propose a
      potential role for IQGAP1 in regulating epithelial integrity and
      compartmentalized signaling in epithelia.

PMID- 27880083
TI  - How do parents and pediatricians arrive at the decision to immunize their
      children in the private sector? Insights from a qualitative study on rotavirus
      vaccination across select Indian cities.
AB  - Key debates on improving vaccination coverage tend to focus on factors that
      affect uptake in the public health system while ignoring the private sector that
      plays an important role in providing health services in any low or middle-income
      country setting. Using in-depth interviews, we explored factors that influenced
      the decision of parents as well as pediatricians working in the private sector
      across 8 Indian cities on whether their children should be vaccinated with a
      particular vaccine Pediatricians and their relationship with parents was an
      important factor that influenced the decision on whether parents vaccinated their
      children with a particular vaccine or not. The decision to recommend a vaccine is
      taken on the principle that it is better to be safe than sorry than on any
      objective assessment of whether a child requires a particular vaccine or not.
      Family members and social factors also played a major role in the decision
      making. According to some parents, vaccinating their child added an aspirational
      value to their growth. This is especially true of the newer vaccines that are
      considered optional in India. The cost of a vaccine did not come up as an
      inhibiting factor in the decision to vaccinate a child. Access to appropriate
      evidence was limited for both pediatricians and parents and evidence per se
      played a minimal role in the final decision to vaccinate a child or not. Far more
      important were the influences of factors such as relationship with the
      pediatrician, the role of decisions related to vaccination taken by people in the
      immediate social network.

PMID- 27880084
TI  - Corrigendum.

PMID- 27880085
TI  - Different forms of spirituality and heavy episodic drinking among college
      students.
AB  - OBJECTIVE: The current study examined prospective, bidirectional relationships
      between 3 measures of spirituality (Daily Spiritual Experiences, Positive
      Religious Coping, and Negative Religious Coping) and frequency of heavy episodic
      drinking. PARTICIPANTS: Three hundred ninety-one students attending a large,
      public university in the Midwest. METHODS: Electronic surveys assessing
      predictors of college alcohol use were sent to participants in the winter of
      their freshman and sophomore years. Structural equation modeling was used to
      analyze data. RESULTS: A latent factor comprised of Daily Spiritual Experiences
      and Positive Religious Coping (ie, "positive spirituality") was negatively
      related to future frequency of heavy episodic drinking. Negative Religious Coping
      was unrelated to heavy episodic drinking. Additionally, heavy episodic drinking
      did not prospectively predict any measures of spirituality. CONCLUSIONS: Data are
      supportive of continued efforts to integrate positive spirituality into
      interventions for collegiate heavy episodic drinking.

PMID- 27880087
TI  - Ethnic Disparities in Medicare Part D Satisfaction and Intention to Switch Plans.
AB  - Medicare Part D has been successful in providing affordable prescription drug
      coverage with relatively high levels of beneficiary reported satisfaction. We use
      nationally representative survey data to examine whether racial/ethnic
      disparities exist in reported Part D satisfaction and plan evaluations. Compared
      to non-Hispanic White Medicare beneficiaries, Hispanic beneficiaries are
      considerably more likely to report to switch to a new plan in the next year and,
      among beneficiaries auto-enrolled in a Part D plan, are less likely to be very
      satisfied with the currently enrolled plan. The findings of ethnic disparities in
      both Medicare Part D plan satisfaction and the intent to switch plans call for
      future quality and equity improvement efforts to address these disparities.

PMID- 27880086
TI  - Comparing the effects of Calendula officinalis and clotrimazole on vaginal
      Candidiasis: A randomized controlled trial.
AB  - This triple-blind trial examined the effects of Calendula officinalis vaginal
      cream on the treatment of vaginal Candidiasis (primary outcome) and sexual
      function (secondary outcome). Married women aged 18-45 years with vaginal
      Candidiasis (n = 150) were recruited from April to October 2014 and randomized
      into Calendula and clotrimazole groups, using 5-g vaginal cream every night for
      seven nights. Clinical and laboratory assessments were conducted at 10-15 and 30
      35 days after intervention and the female sexual function index was assessed at
      30-35 days. Six women were lost to follow-up. The frequency of testing negative
      for Candidiasis in the Calendula group was significantly lower at the first (49%
      vs. 74%; odds ratio (OR) 0.32; 95% confidence interval (CI) 0.16-0.67) but higher
      at the second (77% vs. 34%; OR 3.1; 95% CI 1.5-6.2) follow-up compared to the
      clotrimazole group. The frequency of most signs and symptoms were almost equal in
      the two groups at the first follow-up, but were significantly lower in the
      Calendula group at the second follow-up. Sexual function had almost equal
      significant improvement in both groups. Calendula vaginal cream appears to have
      been effective in the treatment of vaginal Candidiasis and to have a delayed but
      greater long-term effect compared to clotrimazole.

PMID- 27880089
TI  - The Human Right to Leisure in Old Age: Reinforcement of the Rights of an Aging
      Population.
AB  - The right to leisure is recognized as a human right under the 1948 United Nations
      Universal Declaration of Human Rights. The actual meaning and material content of
      this human right is subject to debate. The aim of this study is to examine the
      extent and the context to which this human right is specifically recognized with
      regard to older persons. Methodologically, this study textually analyzed 17
      different international older persons' human rights documents. The findings
      reveal that in the majority of these documents there is no reference to the right
      to leisure. In the remaining documents, the right to leisure is mostly referred
      to indirectly or in a narrow legal construction. These findings support the
      notion that despite the growing body of knowledge regarding the importance of
      meaningful leisure in old age-and its empowering and anti-ageist nature-this
      knowledge has not transformed into a legal human rights discourse.

PMID- 27880088
TI  - Lectio Divina: A Preliminary Evaluation of a Chaplaincy Program.
AB  - This participant outcome evaluation serves as a preliminary investigation into
      the effects of lectio divina, a chaplaincy service representing a form of focused
      Scripture reading. A sample of n = 19 patients who participated in this service
      at a Department of Veterans Affairs Medical Center in upstate New York was
      screened at baseline and 30-days follow-up using the Duke University Religion
      Index, Berg Spiritual Injury Scale, and a screening question for thoughts of
      harming self or others. These measures were used to assess the intended outcomes
      of enhanced religiosity, ameliorated spiritual injury, and decreased thoughts of
      violence. Data were collected through retrospective clinical chart reviews. The
      outcomes of enhanced religiosity or decreased thoughts of violence were not
      observed in this sample population. Ameliorated spiritual injury was observed in
      veterans with substantial engagement in lectio divina (>2 sessions) as well as
      those who endorsed thoughts of harming self or others.

PMID- 27880090
TI  - The Differential Impact of Alcohol and Interpersonal Violence on the Severity of
      Violent Traumatic Brain Injuries among American Indians.
AB  - Research shows connections between substance use and traumatic brain injury
      (TBI), high rates of substance use and interpersonal violence (IPV) in American
      Indians with TBI, and connections between IPV and TBI. This study assessed the
      effects of substance use at the time of a violent TBI and possible mediators such
      as American Indian race on injury severity (injury severity score [ISS]). A
      secondary data analysis of 3,351 individuals who experienced a TBI due to
      violence was conducted. American Indians with TBI were more likely to experience
      IPV (chi2 = 4.19; p = .04) and had significantly higher blood alcohol content
      level (BAC) scores (t = - 16.78; p = .000) than other racial groups. A regression
      model explained 27% of the variance in ISS. Significant interaction terms
      uncovered positive relationships between: (a) American Indian race and ISS when
      the injury aetiology was not IPV and BAC scores were lower than the legal limit,
      and (b) IPV and ISS when patients were not American Indian. Alcohol was
      negatively associated with ISS among American Indians, suggesting that BAC may
      impact individuals with TBI differentially as a function of race.

PMID- 27880091
TI  - Contextualizing urban living as a determinant of women's health in Jakarta,
      Indonesia.
AB  - Big cities can offer great opportunities for women to have a better life. At the
      same time, however, the physical and social environment in cities can negatively
      affect their health. We conducted focus groups with 24 women (aged 18-72 years)
      living in Jakarta, Indonesia from October to November 2014. Our aim was to elicit
      women's experiences of living in Jakarta, including their health and accessing
      health care. The most frequent health problems reported by women in this study
      were hypertension and arthritis. Women often gave priority to their family,
      particularly their children, over themselves and their own health. Discussants
      also thought that the city's physical and social conditions could affect their
      health, and that women were more prone to feel stress than men. The results of
      this study highlight the importance of addressing social determinants of health
      across the life course, including gender, to improve women's health status.
      Moreover, multi-sectoral collaboration at the municipal and national level is
      needed for urban planning to create better living conditions for women in the
      cities.

PMID- 27880092
TI  - Efficacy of zinc oxide nanoparticles in attenuating pancreatic damage in a rat
      model of streptozotocin-induced diabetes.
AB  - Zinc oxide nanoparticles (ZnO NPs) therapy is a promising strategy for treatment
      of several diseases. We aimed to investigate the therapeutic potential of ZnO NPs
      in ameliorating the histopathological and functional alterations in the pancreas
      of a rat model of streptozotocin-induced diabetes. Rats were randomized into
      control, diabetic and ZnO NPs-treated diabetic groups. Biochemical assays of
      blood glucose and serum insulin were performed. Pancreas specimens were processed
      for light and electron microscope examinations. ZnO NPs effectively reversed
      diabetes-induced pancreatic injury, as evidenced by the structural and
      ultrastructural improvement and confirmed by biochemical normalization of blood
      glucose and serum insulin.

PMID- 27880518
TI  - Association between workplace psychosocial factors and mental health in Black,
      Hispanic, and White women: Cross-sectional findings from the National Health
      Interview Survey.
AB  - Research evaluating the relation of workplace psychosocial factors to mental
      health among U.S. women of different racial/ethnic backgrounds is limited. This
      study investigated the relationship between work-related psychosocial factors and
      mental health among non-Hispanic Black, Hispanic, and non-Hispanic White women
      using data from the 2010 National Health Interview Survey. Independent variables
      of interest included job insecurity, workplace harassment, and work-family
      conflict (WFC). Multiple Poisson regression models were used to examine the
      associations between the outcome and independent variables. The prevalence of
      unfavorable mental health was highest among non-Hispanic Black women (36%)
      compared to Hispanic (34%) and non-Hispanic White (30%) women. A higher
      proportion of non-Hispanic Black women reported WFC compared to Hispanics and non
      Hispanic Whites (chi2 = 15.50, p < .01), while more Hispanics reported job
      insecurity (chi2 = 116.81, p < .01). Prevalence of workplace harassment did not
      differ significantly by race/ethnicity. Odds of unfavorable mental health were
      significantly higher for women reporting psychosocial work factors. Unexpectedly,
      a greater association between psychosocial work factors and unfavorable mental
      health was observed among non-Hispanic White women compared to non-White women;
      however, caution should be taken in interpreting these cross-sectional results.
      Future studies should investigate temporal associations and additional
      psychosocial variables that were not available for use in the current study.

PMID- 27880519
TI  - Special Issue: GTPases in trafficking, autophagy, and disease (FASEB SRC).

PMID- 27880619
TI  - Experiencing an Intimate Partner's Breast Cancer: Attachment, Caregiving, and
      Burden in Men.
AB  - OBJECTIVE: This study examined interrelationships among adult attachment
      orientations, caregiving, and caregiver burden in men of female partners with
      breast cancer, and tested whether caregiving patterns mediated associations
      between men's attachment orientations and their self-reported caregiver burden.
      METHOD: The participants were 124 male partners of women with breast cancer.
      These participants completed assessments related to attachment, caregiving, and
      caregiver burden. Path models examined the associations between constructs and
      tested mediational effects. RESULTS: Findings demonstrated significant
      associations between men's adult attachment orientations and their experience of
      caregiver burden. In addition, the maintenance of proximity in caregiving
      completely mediated the respective associations of attachment security and
      attachment avoidance to caregiver health problems, on one hand, and to the
      caregiver's self-esteem (e.g., another indicator for caregiver burden), on the
      other. Moreover, we found a direct effect of attachment avoidance on health
      problems. CONCLUSIONS: This study highlighted the importance of addressing adult
      attachment dispositions and caregiving to understanding the relational processes
      implicated in caregiver burden. The results support the conclusion that men's
      adult attachment orientations and caregiving patterns toward their female
      partners with breast cancer are relevant contributors to men's perceptions of
      caregiver burden.

PMID- 27880620
TI  - A Relational Model for the Intergenerational Transmission of Captivity Trauma: A
      23-Year Longitudinal Study.
AB  - OBJECTIVES: The aversive, long-term toll of war captivity and fathers' combat
      induced posttraumatic stress disorder (PTSD) on adult offspring's secondary
      traumatization (ST) has been recently exemplified. However, the study of
      potential mechanisms of the intergenerational transmission of trauma to offspring
      is still lacking. This prospective study aimed to assess the role of fathers'
      PTSD symptoms (PTSS), paternal parenting, and adult offspring's attachment
      insecurities in adult offspring's PTSS. METHOD: A sample of 124 Israeli father
      child dyads (80 ex-POW dyads and a comparison group of 44 veteran dyads)
      completed self-report measures. The fathers participated in three waves of
      measurements following the Yom Kippur War (T1: 1991, T2: 2003, T3: 2008), while
      the offspring took part in T4 (2013). RESULTS: Offspring of ex-POWs with PTSD at
      T3 reported more PTSS and higher levels of attachment insecurities than offspring
      of ex-POWs without PTSD and controls at T4. Fathers' proximity to the children
      and sensitivity to the children's needs were negatively related. Offspring's
      attachment insecurities were positively related to offspring's PTSS. Importantly,
      serial multiple mediation model results show that war captivity increased the
      level of the fathers' PTSD at T2 and T3, which in turn decreased the level of the
      fathers' parenting at T3, and thereby increased the level of offspring's
      attachment avoidance at T4, which by its own merit was related to higher levels
      of adult offspring's PTSS. CONCLUSIONS: The mechanisms of the intergenerational
      transmission of captivity-related trauma of veterans' PTSD and paternal
      parenting, through offspring's attachment insecurities and offspring's PTSS, was
      exemplified.

PMID- 27880621
TI  - The Dying Role: Its Relevance to Improved Patient Care.
AB  - SOCIETY is failing to meet the obligation it has to its dying members. Persons
      with terminal illnesses suffer isolation and neglect in hospitals, receive
      overzealous treatment by physicians, and are kept in ignorance of their situation
      by families and medical personnel. Evidence for these statements has come from
      observers of the medical care system and from dying patients themselves (Kubler
      Ross, 1969; Reynolds and Kalish, 1974; Sudnow, 1967). In the nineteenth century
      it was common for persons to die in the familiar environs of their homes,
      surrounded by grieving families from whom they parted in a meaningful manner
      (Blauner, 1966). Dying persons of today no longer fill a well-defined social
      role. Instead, the distinction between the roles of sick and dying persons has
      been lost and, in the resulting confusion, the care of dying people has suffered.
      The purpose of this article is to clarify the distinction between the dying and
      sick roles, identify the signs of existing role confusion, suggest ways in which
      this confusion may be corrected, and show how reestablishment of the dying role
      can result in improved care of dying people. The important part physicians play
      in defining sick and dying roles will be emphasized.

PMID- 27880622
TI  - Physicians' Understanding of the Dying Role: A Training Opportunity.

PMID- 27880623
TI  - The "Dying Role": Its Time Had Come.

PMID- 27880624
TI  - Suicidal Ideation Among Korean Elderly: Risk Factors and Population Attributable
      Fractions.
AB  - OBJECTIVES: The objective of this study was to investigate the risk factors of
      suicidal ideation and their population attributable fraction (PAF) in a
      representative sample of the elderly population in Korea. METHOD: We examined the
      data set from the Survey of Living Conditions and Welfare Needs of Korean Older
      Persons, which was conducted by the Korea Institute for Health and Social Affairs
      (KIHASA) in 2011. In that survey, 10,674 participants were randomly selected from
      those older than age 65. Simultaneous multivariate logistic regression was used
      to investigate the risk factors of suicidal ideation in terms of their
      sociodemographic and health-related variables. Subsequently, the PAF was
      calculated with adjustment for other risk factors. RESULTS: The weighted
      prevalences of depression and suicidal ideation were 30.3% and 11.2%,
      respectively. In multivariate analysis, factors significantly associated with
      decreased risk of suicidal ideation included old-old age (odds ratio [OR] = 0.66
      for 75 to 79 years, OR = 0.52 for 80 to 84 years, OR = 0.32 for older than 85
      years), economic status (OR = 0.59 for 5th quintile; more than US$25,700 per
      year), whereas those associated with increased risk included poor social support
      (OR = 1.28), currently smoking (OR = 1.42), sleep problems (OR = 1.74), chronic
      illness (OR = 1.40), poor subjective health (OR = 1.56), functional impairment
      (OR = 1.45), and depression (OR = 4.36). Depression was associated with a fully
      adjusted PAF of 45.7%, followed by chronic illness (19.4%), poor subjective
      health status (18.9%), sleep problems (14.1%), functional impairment (4.9%), poor
      social support (4.2%), and currently smoking (3.6%). CONCLUSIONS: Preventive
      strategies focused particularly on depression might reduce the impact of suicidal
      ideation in the elderly population. Also, specific mental health centers focused
      on the specific needs of the elderly population should be established to manage
      suicidal risk.

PMID- 27880625
TI  - Evolution of the Care of the Dying: From Paternalistic to Palliative Care.

PMID- 27880626
TI  - Psychological Sequelae of the 2013 Super Typhoon Haiyan Among Survivor
      Responders.
AB  - OBJECTIVE: Super Typhoon Haiyan (known as Yolanda in the Philippines), one of the
      strongest tropical cyclones recorded in history, made landfall in the Philippines
      in November 2013. This cross-sectional study examined the psychological impact of
      the typhoon and its aftermath, as well as the impact of individual typhoon
      related stressors among a group of survivor-responders. METHOD: A total of 192
      Filipino adult survivors who were also disaster-relief responders and 45
      unaffected disaster-relief responders (N = 237) completed a questionnaire that
      assessed their general psychological distress (GPD), symptoms of posttraumatic
      stress (PTS), and disaster experiences 1.5 to 4 months after the event. RESULTS:
      The disaster-exposed group was more distressed and suffered from more symptoms of
      PTS, but the prevalence of posttraumatic stress disorder (PTSD) was not
      statistically different between the two groups (7.9% versus 9.4%). Regression
      analysis revealed that financial instability (beta = .52), physical injury (beta
      = .21), and perceived life threat (beta = .17) were associated with GPD. Physical
      injury (beta = .20) and perceived life threat (beta = .20) were also associated
      with PTS symptoms. CONCLUSIONS: Although a marked difference in PTSD was not
      noted, the psychological impact of Super Typhoon Haiyan on survivor-responders in
      terms of nonspecific psychological distress and symptoms of PTS was considerable.
      Some typhoon-related stressors, including financial instability, physical injury,
      and perceived life threat, appear to be more detrimental to mental health than
      other stressors.

PMID- 27880627
TI  - Do We Need Rules for Dying?

PMID- 27880628
TI  - A Prescient View of Palliative Care by the Psychiatric Physician.

PMID- 27880630
TI  - The "Dying Role": A New Path, Already Well Trodden.

PMID- 27880629
TI  - Suicidal Ideation and Interpersonal Needs: Factor Structure of a Short Version of
      the Interpersonal Needs Questionnaire in an At-Risk Military Sample.
AB  - OBJECTIVE: The interpersonal-psychological theory of suicide posits that
      perceived burdensomeness (PB; i.e., the belief that others would be better off if
      one were dead) and thwarted belongingness (TB; i.e., the belief that one lacks
      meaningful social connections) are both necessary risk factors for the
      development of suicidal ideation. To test these relations, measures are needed
      that are well validated, especially in samples of at-risk adults. METHOD: The
      current study was designed to examine the factor structure of an eight-item
      version of the Interpersonal Needs Questionnaire (INQ) in a sample of 405 U.S.
      past and current military personnel (Mage = 31.57 years, SD = 7.28; 90.4% male)
      who endorsed either current suicidal ideation and/or a past suicide attempt.
      Analyses were conducted using confirmatory factor analysis (CFA). RESULTS: A
      bifactor model comprising a general factor, labeled interpersonal needs, and two
      specific factors, labeled PB and TB, fit the data best. The general factor
      captured a high proportion of overall variance (81.9%). In contrast, the TB
      factor captured only a modest amount of variance in items meant to capture this
      factor (59.1%) and the PB factor captured very little variance in items meant to
      capture this factor (13.5%). Further, only the interpersonal needs factor was
      associated with lifetime and past-week suicidal ideation as well as suicidal
      ideation frequency and duration. CONCLUSIONS: The current findings indicate that,
      for the INQ-8 in high-risk military personnel, a general interpersonal needs
      factor accounted for the relations PB and TB share with suicidal ideation.

PMID- 27880632
TI  - Burden of Multiple Chronic Conditions in Delaware, 2011-2014.
AB  - The objective of this study was to use data from the Behavioral Risk Factor
      Surveillance System (BRFSS) to examine the prevalence of multiple chronic
      conditions (MCC) by select sociodemographic groups and determine the prevalence
      of most common MCC dyads and triads among Delaware adults. Combined data for 2011
      through 2014 from BRFSS (n = 18,052) were analyzed to determine prevalence of
      MCC. Delaware adults were categorized as having 0, 1, 2, or 3 or more of the
      following diagnosed chronic conditions: angina, arthritis, asthma, cancer,
      chronic kidney disease, chronic obstructive pulmonary disease, diabetes, high
      blood pressure, high cholesterol, myocardial infarction (heart attack), obesity,
      or stroke. More than 65% of Delaware adults had at least 1 of the 12 selected
      chronic conditions. Furthermore, 36.8% of Delaware adults had MCC. The
      arthritis/obesity dyad and the arthritis/high blood pressure/high cholesterol
      triad were the 2 most prevalent MCC combinations. The findings of this study
      contribute information to the field of MCC research.

PMID- 27880633
TI  - Diversion Alert: 1-Year Evaluation Across Northern New England, 2013-2014.
AB  - This report describes Diversion Alert, a unique online tool aimed at reducing
      misuse and diversion of prescription drugs, and reports the results of a 1-year
      evaluation of Diversion Alert's impact in Maine. We used a quasi-experimental
      research design to compare survey data in Maine with those of neighboring states
      (New Hampshire and Vermont, 2013 and 2014). Compared with their counterparts in
      New Hampshire and Vermont who did not use Diversion Alert, prescribers and
      pharmacists in Maine who used Diversion Alert increased their communication with
      patients and other providers involved in their patients' care, became aware of
      patients arrested for prescription drugs possession or diversion, used best
      practices associated with prevention or detection of addiction and diversion more
      frequently, and attributed positive changes in their prescribing practices to
      Diversion Alert. In combination with other state and federal programs, Diversion
      Alert may be an effective tool to help prevent the misuse of opioid medications.

PMID- 27880634
TI  - Erratum, Vol. 13, November 3, 2016.
AB  - [This corrects the article DOI: 10.5888/pcd13.160212.].

PMID- 27880641
TI  - Molecular profiling optimizes the treatment of low-grade glioma.

PMID- 27880642
TI  - Lesion momentum as explanation for preoperative neurocognitive function in
      patients with malignant glioma.

PMID- 27880649
TI  - Corrigendum.

PMID- 27880640
TI  - The clinical use of stress echocardiography in non-ischaemic heart disease:
      recommendations from the European Association of Cardiovascular Imaging and the
      American Society of Echocardiography.
AB  - A unique and highly versatile technique, stress echocardiography (SE) is
      increasingly recognized for its utility in the evaluation of non-ischaemic heart
      disease. SE allows for simultaneous assessment of myocardial function and
      haemodynamics under physiological or pharmacological conditions. Due to its
      diagnostic and prognostic value, SE has become widely implemented to assess
      various conditions other than ischaemic heart disease. It has thus become
      essential to establish guidance for its applications and performance in the area
      of non-ischaemic heart disease. This paper summarizes these recommendations.

PMID- 27880650
TI  - Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step Evidence and
      Expert-Based Recommendations for Evaluation and Treatment: Part XI: Dementia.
AB  - : OBJECTIVE : To present the 11th in a series of articles designed to deconstruct
      chronic low back pain (CLBP) in older adults. The series presents CLBP as a
      syndrome, a final common pathway for the expression of multiple contributors
      rather than a disease localized exclusively to the lumbosacral spine. Each
      article addresses one of 12 important contributions to pain and disability in
      older adults with CLBP. This article focuses on dementia. METHODS: A modified
      Delphi technique was used to develop an algorithm for an approach to treatment
      for older adults living with CLBP and dementia. A panel of content experts on
      pain and cognition in older adults developed the algorithm through an iterative
      process. Though developed using resources available within Veterans Health
      Administration (VHA) facilities, the algorithm is applicable across all health
      care settings. A case taken from the clinical practice of one of the contributors
      demonstrates application of the algorithm. RESULTS: We present an evidence-based
      algorithm and biopsychosocial rationale to guide providers evaluating CLBP in
      older adults who may have dementia. The algorithm considers both subtle and overt
      signs of dementia, dementia screening tools to use in practice, referrals to
      appropriate providers for a complete a workup for dementia, and clinical
      considerations for persons with dementia who report pain and/or exhibit pain
      behaviors. A case of an older adult with CLBP and dementia is presented that
      highlights how an approach that considers the impact of dementia on verbal and
      nonverbal pain behaviors may lead to more appropriate and successful pain
      management. CONCLUSIONS: Comprehensive pain evaluation for older adults in
      general and for those with CLBP in particular requires both a medical and a
      biopsychosocial approach that includes assessment of cognitive function. A
      positive screen for dementia may help explain why reported pain severity does not
      improve with usual or standard-of-care pain management interventions. Pain
      reporting in a person with dementia does not always necessitate pain treatment.
      Pain reporting in a person with dementia who also displays signs of pain
      associated suffering requires concerted pain management efforts targeted to
      improving function while avoiding harm in these vulnerable patients.Key Words.
      Dementia; Chronic Pain; Low Back Pain; Lumbar; Primary Care.

PMID- 27880651
TI  - Durations of Opioid, Nonopioid Drug, and Behavioral Clinical Trials for Chronic
      Pain: Adequate or Inadequate?
AB  - OBJECTIVES: A recent US federal review and clinical guideline on opioids for
      chronic pain asserted that the literature contributes no evidence on efficacy
      because all trials had "inadequate duration." To explore the evidence, we
      examined durations of studies on opioid, nonopioid drug, and behavioral therapies
      for chronic pain. METHODS: We retrieved Cochrane reviews of anticonvulsants,
      antidepressants, NSAIDs, opioids, or behavioral interventions for chronic pain.
      We also examined all opioid treatment studies retrieved for the federal evidence
      report but excluded due to "inadequate duration." RESULTS: Of 378 Cochrane
      reviews retrieved, 72 evaluated one of the five therapies. Six of these 72 were
      excluded because they were proposals without data or investigated acute pain.
      Fourteen addressed multiple interventions, leaving 52 for analysis. We graphed
      numbers of trials vs duration for the five treatments reviewed in the Cochrane
      Library, compared with durations of opioid trials dropped from the federal
      evidence report. Most graphs were overdispersed Poisson distributions. Nearly all
      trials had active treatment durations of 12 weeks or less. CONCLUSIONS: No common
      nonopioid treatment for chronic pain has been studied in aggregate over longer
      intervals of active treatment than opioids. To dismiss trials as "inadequate" if
      their observation period is a year or less is inconsistent with current
      regulatory standards. The literature on major drug and nondrug treatments for
      chronic pain reveals similarly shaped distributions across modalities.
      Considering only duration of active treatment in efficacy or effectiveness
      trials, published evidence is no stronger for any major drug category or
      behavioral therapy than for opioids.

PMID- 27880653
TI  - New Research on Secondhand Smoke: Implications for Research and Practice.

PMID- 27880652
TI  - Characterization of Chronic Pain and Opioid Usage in Adult Sickle Cell Disease
      Patients Referred to a Comprehensive Pain Clinic.

PMID- 27880662
TI  - Preface.

PMID- 27880663
TI  - An introduction to antifungal stewardship.

PMID- 27880664
TI  - The current treatment landscape: the need for antifungal stewardship programmes.
AB  - There is increasing evidence supporting the need for antifungal stewardship (AFS)
      programmes in order to promote appropriate antifungal use, improve diagnosis and
      quality of care, and decrease the costs of antifungal treatment. AFS programmes
      delivered by experienced teams can be efficacious and cost effective. However,
      there are a variety of challenges often faced during the implementation of AFS
      programmes which can present barriers to their success. These can include lack of
      dedicated personnel, lack of investment in new diagnostic and prescription tools,
      and misperception by other physicians.

PMID- 27880666
TI  - The current management landscape: aspergillosis.
AB  - Diagnosing invasive aspergillosis (IA) has long been challenging due to the
      inability to culture the causal Aspergillus agent from blood or other body
      fluids. This shortcoming has fuelled an interest in non-culture-based diagnostic
      techniques such as the detection of galactomannan (GM) in blood and
      bronchoalveolar lavage fluid, the detection of 1,3-beta-d-glucan (BDG) in blood
      and the detection of Aspergillus DNA by PCR-based techniques. Past decades have
      witnessed important improvements in our understanding of the strengths and
      limitations of antigen assays and in the standardization of PCR-based DNA
      techniques. These assays are now being incorporated into care pathways and
      diagnostic algorithms; they help us to steward and monitor antifungal therapies
      and to predict treatment outcomes.

PMID- 27880665
TI  - The current treatment landscape: candidiasis.
AB  - The epidemiology of Candida species infection has changed over recent decades,
      influenced by local hospital-related factors, patient predisposing conditions and
      type of antifungal agents administered. A shift from Candida albicans as the
      predominant pathogen towards an increasing prevalence of the species Candida
      glabrata and Candida parapsilosis amongst critically ill patients has been
      documented. Changes in Candida species distribution may impact treatment
      recommendations due to differences in susceptibility to antifungal agents among
      species. Previous exposure to antifungal agents has likely contributed to this
      shift in species distribution. Another evolving epidemiological factor to
      consider is the global increase in antifungal resistance to certain antifungal
      drug types, which has been contributed to by the inappropriate use of these
      agents. Proposed management strategies to optimize treatment of patients with
      Candida infection include starting prompt 'early' antifungal therapy, early
      cessation of inappropriate therapy, using an adequate dose and duration of
      therapy and de-escalating treatment whenever possible. The implementation of
      institutional antifungal stewardship programmes has the potential to promote
      appropriate utilization of antifungal agents and to significantly improve the
      care of patients with Candida infection. However, a cultural change among
      healthcare providers and authorities is currently needed to improve antifungal
      use worldwide.

PMID- 27880667
TI  - The current treatment landscape: other fungal diseases (cryptococcosis,
      fusariosis and mucormycosis).
AB  - Compared with major invasive mycoses such as aspergillosis and candidiasis, the
      antifungal stewardship management strategies of other fungal diseases have
      different opportunities and considerations. Cryptococcosis, fusariosis and
      mucormycosis are globally prevalent invasive fungal diseases (IFDs), but are not
      currently included in antifungal prophylaxis guidelines for immunocompromised
      hosts. Since the implementation of biomarkers as part of diagnostic screening
      strategies, the concept of pre-emptive antifungal therapy has emerged for these
      IFDs. Management of cryptococcosis, the most common IFD worldwide, generally
      utilizes a pre-emptive or therapeutic strategy that does not involve prophylaxis
      or empirical antifungal treatment strategies. Antifungal stewardship outcomes for
      cryptococcosis may vary according to the availability of local resources.
      Invasive fusariosis, the second-most common form of non-Aspergillus mould
      infection among haematological malignancy patients, can be managed with pre
      emptive (or diagnostic-driven) approaches based on the monitoring of serum
      galactomannan (GM) antigen in increased-risk populations. The success of
      antimicrobial stewardship programmes in decreasing the burden of invasive
      fusariosis in selected patient populations depends on the development and
      implementation of rapid diagnostic strategies for early and appropriate
      administration of therapy. Mucormycosis may emerge as a breakthrough IFD in
      haematology or solid organ transplant recipients receiving antifungals that lack
      activity against Mucorales. The concept of pre-emptive antifungal therapy has
      thus arisen for mucormycosis in the haematology setting because of the recent
      availability of circulating Mucorales DNA measurement. These examples demonstrate
      the challenges of implementing antifungal stewardship programmes in areas with
      limited resources, as well as in IFDs that are difficult to diagnose and treat.

PMID- 27880668
TI  - The role of the multidisciplinary team in antifungal stewardship.
AB  - There are a variety of challenges faced in the management of invasive fungal
      diseases (IFD), including high case-fatality rates, high cost of antifungal drugs
      and development of antifungal resistance. The diagnostic challenges and poor
      outcomes associated with IFD have resulted in excessive empirical use of
      antifungals in various hospital settings, exposing many patients without IFD to
      potential drug toxicities as well as causing spiralling antifungal drug costs.
      Further complexity arises as different patient groups show marked variation in
      their risk for IFD, fungal epidemiology, sensitivity and specificity of
      diagnostic tests and the pharmacokinetics and pharmacodynamics of antifungal
      drugs. To address these issues and to ensure optimal management of IFD,
      specialist knowledge and experience from a range of backgrounds is required,
      which extends beyond the remit of most antibiotic stewardship programmes. The
      first step in the development of any antifungal stewardship (AFS) programme is to
      build a multidisciplinary team encompassing the necessary expertise in the
      management of IFD to develop and implement the AFS programme. The specific roles
      of the key individuals within the AFS team and the importance of collaboration
      are discussed in this article.

PMID- 27880669
TI  - Conclusion and future perspectives on antifungal stewardship.

PMID- 27880676
TI  - Editorial for Integrative and Comparative Biology.

PMID- 27880677
TI  - Neuroecology: Neural Mechanisms of Sensory and Motor Processes that Mediate
      Ecologically Relevant Behaviors: An Introduction to the Symposium.
AB  - What is Neuroecology? Animal behavior mediates many critical ecological processes
      that, in turn, have implications for the evolution of organismal interactions.
      Because the peripheral and central nervous systems ultimately control behavior,
      research in neuroecology seeks to link the neural basis of behavior with
      behavioral control of ecological interactions, and to determine how specific
      processes (e.g., environmental and genetic constraints, ecological and
      evolutionary forces) operating to alter nervous system function might constrain
      or facilitate adaptive behavior. Our goal for this symposium was to promote a
      general framework for neuroecology by exploring fundamental questions germane to
      this new area of research, and to develop a "toolbox" of techniques and
      approaches for addressing those questions. In the following series of papers, we
      provide a starting point for future work on neuroecology, including evolutionary
      context, the role of plasticity in shaping nervous system function and behavior,
      and an exploration of various sensorimotor systems that control ecological
      interactions. By promoting an integration of observational and experimental
      approaches at different levels of organization, we can reveal much about how the
      neural bases of behaviors influence interactions that occur under ecologically
      relevant contexts that would otherwise be impossible from isolated physiological,
      behavioral, or ecological components.

PMID- 27880678
TI  - Evidence for an Alternative Mechanism of Toxin Production in the Box Jellyfish
      Alatina alata.
AB  - Cubozoans (box jellyfish) have a reputation as the most venomous animals on the
      planet. Herein, we provide a review of cubozoan prey capture and digestion
      informed by the scientific literature. Like all cnidarians, box jellyfish
      envenomation originates from structures secreted within nematocyte post-Golgi
      vesicles called nematocysts. When tentacles come in contact with prey or would-be
      predators, a cocktail of toxins is rapidly deployed from nematocysts via a long
      spiny tubule that serves to immobilize the target organism. The implication has
      long been that toxin peptides and proteins making up the venom within the
      nematocyst capsule are secreted directly by nematocytes during nematogenesis.
      However, our combined molecular and morphological analysis of the venomous box
      jellyfish Alatina alata suggests that gland cells with possible dual roles in
      secreting toxins and toxic-like enzymes are found in the gastric cirri. These
      putative gland cell assemblages might be functionally important internally
      (digestion of prey) as well as externally (envenomation) in cubozoans. Despite
      the absence of nematocysts in the gastric cirri of mature A. alata medusae, this
      area of the digestive system appears to be the region of the body where venom
      implicated gene products are found in highest abundance, challenging the idea
      that in cnidarians venom is synthesized exclusively in, or nearby, nematocysts.
      In an effort to uncover evidence for a central area enriched in gland cells
      associated with the gastric cirri we provide a comparative description of the
      morphology of the digestive structures of A. alata and Carybdea box jellyfish
      species. Finally, we conduct a multi-faceted analysis of the gene ontology terms
      associated with venom-implicated genes expressed in the tentacle/pedalium and
      gastric cirri, with a particular emphasis on zinc metalloprotease homologs and
      genes encoding other bioactive proteins that are abundant in the A. alata
      transcriptome.

PMID- 27880686
TI  - Commentary: It takes more than one to tango: life course epidemiology and related
      approaches.

PMID- 27880687
TI  - Commentary: Developing the future: life course epidemiology, DOHaD and
      evolutionary medicine.

PMID- 27880685
TI  - The last two decades of life course epidemiology, and its relevance for research
      on ageing.

PMID- 27880688
TI  - Commentary: The value of life course epidemiology in low- and middle-income
      countries: an ageing perspective.

PMID- 27880689
TI  - Commentary: The course of life and life, of course: a commentary on Ben-Shlomo,
      Cooper and Kuh.

PMID- 27880690
TI  - Commentary: The use and misuse of life course models.

PMID- 27880691
TI  - Commentary: Incorporating concepts and methods from causal inference into life
      course epidemiology.

PMID- 27880692
TI  - Commentary: Value of the life course approach to the health care of older people.

PMID- 27880693
TI  - Commentary: Life course epidemiology: the past two decades and future directions.

PMID- 27880694
TI  - Commentary: Life course epidemiology embraces geroscience.

PMID- 27880695
TI  - The association of birth weight and infant growth with childhood autonomic
      nervous system activity and its mediating effects on energy-balance-related
      behaviours-the ABCD study.
AB  - BACKGROUND: The purpose of this study was to examine the association of birth
      weight and infant growth with childhood autonomic nervous system (ANS) activity
      and to assess whether ANS activity mediates the associations of birth weight and
      infant growth with energy-balance-related behaviours, including energy intake,
      satiety response, physical activity and screen time. METHODS: In 2089 children,
      we prospectively collected birth weight, infant growth defined as conditional
      weight and height gain between birth and 12 months and-at 5 years-indices of
      cardiac ANS activity and parent-reported energy-balance-related behaviours. A
      mediation analysis was conducted, based on MacKinnon's multivariate extension of
      the product-of-coefficients strategy. RESULTS: Birth weight and infant height
      gain were inversely associated with sympathetic, but not parasympathetic,
      activity at age 5. Infant weight gain was not associated with childhood ANS
      activity. Infant weight gain was predictive of increased childhood screen time
      and infant height gain of diminished childhood energy intake, but sympathetic
      activity did not mediate these associations. CONCLUSIONS: Low-birth-weight
      children have higher sympathetic activity, which is considered a risk factor for
      cardiovascular disease. Height gain in infancy seems to be beneficial for
      childhood sympathetic activity. However, sympathetic activity was no mediator of
      the associations of infant growth with childhood energy-balance-related
      behaviours. As individual differences in ANS activity predict increased risk of
      cardiovascular disease, these differences may offer insight into the early-life
      origins of chronic diseases and provide further basis for public health
      strategies to optimize birth weight and infant growth.

PMID- 27880696
TI  - Response to: Reliability and validity of telomere length measurements.

PMID- 27880701
TI  - In European public health we trust?

PMID- 27880702
TI  - The future of public health practice in Europe.

PMID- 27880703
TI  - ISIS? Crop failure? And no antibiotics? What training will we need for the future
      of public health.

PMID- 27880704
TI  - Voluntary home smoking ban: prevalence, trend and determinants in Italy.
AB  - To investigate voluntary home smoking bans, we analysed five nationally
      representative surveys on 15 175 adults conducted in Italy in 2011-2015. Overall,
      61% of Italians (69% of non-smokers and 32% of current smokers) adopted a
      complete home smoking ban. Although families with children more frequently live
      in smoke-free homes, still the majority of current smokers living with children
      admit smoking inside their homes. Complete home smoking bans are substantially
      increasing in Italy, and an acceleration of this trend is expected with the 2016
      implementation of a new tobacco control legislation aimed at decreasing the
      social acceptability of smoking.

PMID- 27880706
TI  - eComment. How can we be sure?

PMID- 27880707
TI  - eComment. Diagnostic intricacies and fortuitous treatment approaches for
      carbapenem-resistant Klebsiella pneumoniae.

PMID- 27880708
TI  - eReply. Diagnostic intricacies and fortuitous treatment approaches for carbapenem
      resistant Klebsiella pneumoniae.

PMID- 27880709
TI  - eComment. Resident surgical training in mitral valve surgery.

PMID- 27880712
TI  - First by Land, Then by Sea: Origins of Dietary Adaptations for Whales and
      Dolphins during Land to Sea Transition.

PMID- 27880716
TI  - Data-driven informatics tools targeting patients and providers.

PMID- 27880717
TI  - Health informatics: our domain, our challenge.

PMID- 27880711
TI  - Fine-Tuning Motile Cilia and Flagella: Evolution of the Dynein Motor Proteins
      from Plants to Humans at High Resolution.
AB  - The flagellum is a key innovation linked to eukaryogenesis. It provides motility
      by regulated cycles of bending and bend propagation, which are thought to be
      controlled by a complex arrangement of seven distinct dyneins in repeated
      patterns of outer- (OAD) and inner-arm dynein (IAD) complexes. Electron
      tomography showed high similarity of this axonemal repeat pattern across
      ciliates, algae, and animals, but the diversity of dynein sequences across the
      eukaryotes has not yet comprehensively been resolved and correlated with
      structural data. To shed light on the evolution of the axoneme I performed an
      exhaustive analysis of dyneins using the available sequenced genome data.
      Evidence from motor domain phylogeny allowed expanding the current set of nine
      dynein subtypes by eight additional isoforms with, however, restricted taxonomic
      distributions. I confirmed the presence of the nine dyneins in all eukaryotic
      super-groups indicating their origin predating the last eukaryotic common
      ancestor. The comparison of the N-terminal tail domains revealed a most likely
      axonemal dynein origin of the new classes, a group of chimeric dyneins in
      plants/algae and Stramenopiles, and the unique domain architecture and origin of
      the outermost OADs present in green algae and ciliates but not animals. The
      correlation of sequence and structural data suggests the single-headed class-8
      and class-9 dyneins to localize to the distal end of the axonemal repeat and the
      class-7 dyneins filling the region up to the proximal heterodimeric IAD. Tracing
      dynein gene duplications across the eukaryotes indicated ongoing diversification
      and fine-tuning of flagellar functions in extant taxa and species.

PMID- 27880718
TI  - Contribution of JAC to antimicrobial stewardship.
AB  - Antimicrobial stewardship programmes are increasingly being used to improve the
      quality of antimicrobial prescribing, with the dual aim of optimizing clinical
      outcomes and minimizing the emergence and spread of antimicrobial resistance. The
      Journal of Antimicrobial Chemotherapy (JAC) is celebrating its 40th anniversary
      and, as part of activities to commemorate this event, this article highlights the
      contribution of JAC to antimicrobial stewardship. Papers published in JAC have
      contributed to the evidence base for stewardship, have highlighted educational
      and behavioural change initiatives aimed at improving antibiotic prescribing
      practice, and have actively sought to foster the practice of antimicrobial
      stewardship amongst its readers.

PMID- 27880720
TI  - The impact of reproductive life on breast cancer risk in women with family
      history or BRCA mutation.
AB  - Reproductive history and exogenous hormonal exposures are acknowledged risk
      factors for breast cancer in the general population. In women at increased breast
      cancer risk for genetic predisposition or positive family history, data regarding
      these risk factors are limited or conflicting, and recommendations for these
      categories are unclear. We evaluated the characteristics of reproductive life in
      2522 women at increased genetic or familial breast cancer risk attending our
      Family Cancer Center. Breast cancers in BRCA mutation carriers were more likely
      to be hormone receptor negative, diagnosed at 35 years or before and multiple
      during the lifetime than tumors in women at increased familial risk, while the
      distribution of invasive cancers and HER2 positive tumors was similar in the
      different risk groups. At least one full-term pregnancy (HR 0.27; 95% CI 0.12
      0.58; p = 0.001), breastfeeding either less (HR 0.24; 95% CI 0.09-0.66; p =
      0.005) or more (HR 0.25; 95% IC 0.08-0.82; p = 0.022) than one year and late age
      at menopause (HR 0.10; 95% CI 0.01-0.82; p = 0.033) showed to be protective
      factors in BRCA mutation carriers, while in women at increased familial risk
      early age at first full-term pregnancy (HR 0.62; 95% IC 0.38-0.99; p = 0.048) and
      late menarche (HR 0.61; 95% CI 0.42-0.85; p = 0.004) showed to be the main
      protective factors. Finally, for the entire population, combined hormonal
      contraceptives demonstrated to do not increase breast cancer risk. The results of
      our study suggest that women at high familial risk and mutation carries develop
      tumors with different clinical-pathological characteristics and, consequently,
      are influenced by different protective and risk factors.

PMID- 27880721
TI  - Inhibition of HAX-1 by miR-125a reverses cisplatin resistance in laryngeal cancer
      stem cells.
AB  - Chemoresistance is a major obstacle in chemotherapy of laryngeal carcinoma.
      Recently, studies indicate that cancer stem cells are responsible for
      chemotherapy failure. In addition, microRNAs play important roles in tumor
      initiation, development and multidrug resistance. In the present study, we found
      that the expression of microRNA-125a was decreased in laryngeal carcinoma tissues
      and Hep-2 laryngeal cancer stem cells (Hep-2-CSCs). MicroRNA-125a gain-of
      function significantly increased the sensitivity of Hep-2-CSCs to cisplatin in
      vitro and in vivo. Combination with microRNA-125a mimics can decrease the half
      maximal inhibitory concentration of Hep-2-CSCs to cisplatin. Mechanically, we
      found that microRNA-125a reverses cisplatin resistance in Hep-2-CSCs by targeting
      Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1). Inhibition
      of HAX-1 by microRNA-125a significantly promotes the cisplatin-induced apoptosis
      in Hep-2-CSCs through mitochondrial pathway. In addition, multidrug resistance of
      Hep-2-CSCs to vincristine, etoposide and doxorubicin was greatly improved after
      the cells were transfected with microRNA-125a mimics. These dates strongly
      suggested the promotion of microRNA-125a/HAX-1 axis on chemotherapy of laryngeal
      carcinoma.

PMID- 27880723
TI  - Association between three functional microRNA polymorphisms (miR-499 rs3746444,
      miR-196a rs11614913 and miR-146a rs2910164) and breast cancer risk: a meta
      analysis.
AB  - Three functional microRNA polymorphisms (miR-499 rs3746444 A > G, miR-196a
      rs11614913 C > T and miR-146a rs2910164 G > C) have been reported to be
      associated with breast cancer (BC) risk. However, the results of the published
      studies are inconsistent. In order to obtain a more credible result, we conducted
      this meta-analysis. We searched PubMed, EMBASE and Web of Science databases to
      identify relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals
      (CIs) were used to assess the association. Thirty-eight eligible studies with
      17,417 cases and 18,988 controls were included in this meta-analysis. Our results
      showed that the rs3746444 was associated with an increased breast cancer risk in
      the four genetic models (G vs. A: OR = 1.17, P = 0.008; GG vs. AA: OR = 1.41, P <
      0.001; AG vs. AA: OR = 1.10, P = 0.036; GG+AG vs. AA: OR = 1.16, P = 0.001). In
      the subgroup analysis by ethnicity, significant correlation remained in Asians
      but not in Caucasians. For rs11614913, obvious decreased breast cancer risk was
      observed in Caucasian populations (T vs. C: OR = 0.93, P = 0.044). However, we
      couldn't detect an association between rs2910164 and breast cancer risk. This
      meta-analysis demonstrates that rs3746444 could increase breast cancer risk in
      Asians and in general populations, while rs11614913 could decrease the risk of
      breast cancer in Caucasians. The rs2910164 polymorphism has no association with
      breast cancer risk. More multicenter studies with larger sample sizes are
      required to verify our results.

PMID- 27880722
TI  - Deletion of 8p is an independent prognostic parameter in prostate cancer.
AB  - Deletion of chromosome 8p is the second most frequent genomic alteration in
      prostate cancer. To better understand its clinical significance, 8p deletion was
      analyzed by fluorescence in-situ hybridization on a prostate cancer tissue
      microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was
      linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456
      pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001).
      Deletions of 8p were detected in 25.5% of 1,653 Gleason <= 3 + 3, 36.6% of 3,880
      Gleason 3 + 4, 50.2% of 1,090 Gleason 4 + 3, and 51.1% of 354 Gleason >= 4 + 4
      tumors (P < 0,0001). 8p deletions were strongly linked to biochemical recurrence
      (P < 0.0001) independently from established pre- and postoperative prognostic
      factors (P = 0.0100). However, analysis of morphologically defined subgroups
      revealed, that 8p deletion lacked prognostic significance in subgroups with very
      good (Gleason <= 3 + 3, 3 + 4 with <= 5% Gleason 4) or very poor prognosis (pT3b,
      Gleason >= 8, pN1). 8p deletions were markedly more frequent in cancers with
      (53.5%) than without PTEN deletions (36.4%; P < 0,0001) and were slightly more
      frequent in ERG-positive (40.9%) than in ERG-negative cancers (34.7%, P < 0.0001)
      due to the association with the ERG-associated PTEN deletion. Cancers with
      8p/PTEN co-deletions had a strikingly worse prognosis than cancers with deletion
      of PTEN or 8p alone (P <= 0.0003). In summary, 8p deletion is an independent
      prognostic parameter in prostate cancer that may act synergistically with PTEN
      deletions. Even statistically independent prognostic biomarkers like 8p may have
      limited clinical impact in morphologically well defined high or low risk cancers.

PMID- 27880724
TI  - Hepatic resection after transarterial chemoembolization increases overall
      survival in large/multifocal hepatocellular carcinoma: a retrospective cohort
      study.
AB  - To investigate the prognosis of transarterial chemoembolization (TACE) followed
      by hepatic resection (HR) in large/multifocal hepatocellular carcinoma (HCC), the
      medical records of consecutive HCC patients who underwent TACE between January
      2006 and December 2010 were retrospectively analyzed. Patients who received TACE
      alone comprised the T group (61 patients), while those who received HR after TACE
      comprised the T+R group (49 patients). All the resections were successfully
      performed, and only one class V complication occurred. While liver function was
      altered from baseline within 1 week after HR, it recovered within 1 month.
      Overall survival (OS) of the T+R and T groups were compared, and sub-group
      analyses were performed based on baseline alpha-fetoprotein (AFP) levels, the
      reduction of AFP, and tumor response before HR. Overall survival (OS) in the T+R
      group was longer than in the T group (47.00 +/- 2.87 vs. 20.00 +/- 1.85 months, P
      < 0.001). OS in the T+R group with AFP reduction was less than 50%, and OS among
      those with a poor tumor response before HR did not differ from the T group (P >
      0.05). These patients may not benefit from the combined treatment. Our findings
      suggest HR after TACE is safe and effective for large/multifocal HCC, and
      prolongs OS when compared to TACE alone.

PMID- 27880725
TI  - Mouse Sirt3 promotes autophagy in AngII-induced myocardial hypertrophy through
      the deacetylation of FoxO1.
AB  - Sirt3, a mitochondrial NAD+-dependent histone deacetylase, is the only member
      proven to promote longevity in mammalian Sirtuin family. The processed short form
      of Sirt3 has been demonstrated to target many mediators of energy metabolism and
      mitochondrial stress adaptive program. Autophagy serves as a dynamic recycling
      mechanism and provides energy or metabolic substrates. Among the mechanisms
      triggered by cardiac stress, opinions vary as to whether autophagy is a
      protective or detrimental response. Here, by inducing the Sirt3-knockout mice to
      myocardial hypertrophy with chronic angiotensin II infusion for four weeks, we
      determined the role of Sirt3 in myocardial hypertrophy and autophagy. In this
      study, the Sirt3-knockout mice developed deteriorated cardiac function and
      impaired autophagy compared to wild-type mice. What's more, the overexpression of
      Sirt3 by lentivirus transfection attenuated cardiomyocytes hypertrophy by
      promoting autophagy. We further demonstrated that Sirt3 could bind to FoxO1 and
      activate its deacetylation. Sequentially, deacetylated FoxO1 translocates to the
      nucleus where it facilitates downstream E3 ubiquitin ligases such as Muscle RING
      Finger 1 (MuRF1) and muscle atrophy F-box (MAFbx, Atrogin1). Altogether, these
      results revealed that Sirt3 activation is essential to improve autophagy flux by
      reducing the acetylation modification on FoxO1, which in turn alleviates
      myocardial hypertrophy.

PMID- 27880727
TI  - Gold nanoparticles delivered miR-375 for treatment of hepatocellular carcinoma.
AB  - MiR-375 is a tumor suppressor miRNA that is downregulated in hepatocellular
      carcinoma (HCC). However, due to the lack of effective delivery strategies, miR
      375 replacement as a therapy for HCC has not been investigated. In the present
      study, we have developed a straightforward strategy to deliver miR-375 into HCC
      cells by assembling miR-375 mimics on the surface of AuNPs and forming AuNP-miR
      375 nanoparticles. AuNP-miR-375 exhibits high cellular uptake and preserves miR
      375's activities to suppress cellular proliferation, migration/invasion, and
      colony formation, and to induce apoptosis in HCC cells. Furthermore, AuNP
      delivered miR-375 efficiently downregulated its target genes through RNA
      interference. In primary and xenograft tumor mouse models, AuNP-miR-375 showed
      high tumor uptake, therapeutic efficacy, and no apparent toxicity to the host
      mice. In conclusion, our findings indicate that AuNPs is a reliable strategy to
      deliver miR-375 into HCC cells and tissue, and that AuNP-miR-375 has the
      potential in the clinic for treatment of unresectable HCC.

PMID- 27880726
TI  - Chrysophanic acid reduces testosterone-induced benign prostatic hyperplasia in
      rats by suppressing 5alpha-reductase and extracellular signal-regulated kinase.
AB  - Benign prostatic hyperplasia (BPH) is one of the most common chronic diseases in
      male population, of which incidence increases gradually with age. In this study,
      we investigated the effect of chrysophanic acid (CA) on BPH. BPH was induced by a
      4-week injection of testosterone propionate (TP). Four weeks of further injection
      with vehicle, TP, TP + CA, TP + finasteride was carried on. In the CA treatment
      group, the prostate weight was reduced and the TP-induced histological changes
      were restored as the normal control group. CA treatment suppressed the TP
      elevated prostate specific antigen (PSA) expression. In addition, 5alpha
      reductase, a crucial factor in BPH development, was suppressed to the normal
      level close to the control group by CA treatment. The elevated expressions of
      androgen receptor (AR), estrogen receptor alpha and steroid receptor coactivator
      1 by TP administration were also inhibited in the CA group when compared to the
      TP-induced BPH group. Then we evaluated the changes in three major factors of the
      mitogen-activated protein kinase chain during prostatic hyperplasia;
      extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and
      p38 mitogen-activated protein kinase (p38). While ERK was elevated in the process
      of BPH, JNK and p38 was not changed. This up-regulated ERK was also reduced as
      normal by CA treatment. Further in vitro studies with RWPE-1 cells confirmed TP
      induced proliferation and elevated AR, PSA and p-ERK were all reduced by CA
      treatment. Overall, these results suggest a potential pharmaceutical feature of
      CA in the treatment of BPH.

PMID- 27880728
TI  - Analysis of miRNA profiles identified miR-196a as a crucial mediator of aberrant
      PI3K/AKT signaling in lung cancer cells.
AB  - Hyperactivation of the PI3K/AKT pathway is observed in most human cancer
      including lung carcinomas. Here we have investigated the role of miRNAs as
      downstream targets of activated PI3K/AKT signaling in Non Small Cell Lung Cancer
      (NSCLC). To this aim, miRNA profiling was performed in human lung epithelial
      cells (BEAS-2B) expressing active AKT1 (BEAS-AKT1-E17K), active PI3KCA (BEAS
      PIK3CA-E545K) or with silenced PTEN (BEAS-shPTEN).Twenty-four differentially
      expressed miRNAs common to BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN
      cells were identified through this analysis, with miR-196a being the most
      consistently up-regulated miRNA. Interestingly, miR-196a was significantly
      overexpressed also in human NSCLC-derived cell lines (n=11) and primary lung
      cancer samples (n=28).By manipulating the expression of miR-196a in BEAS-2B and
      NCI-H460 cells, we obtained compelling evidence that this miRNA acts downstream
      the PI3K/AKT pathway, mediating some of the proliferative, pro-migratory and
      tumorigenic activity that this pathway exerts in lung epithelial cells, possibly
      through the regulation of FoxO1, CDKN1B (hereafter p27) and HOXA9.

PMID- 27880730
TI  - Loss of ZG16 is regulated by miR-196a and contributes to stemness and progression
      of colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most common malignant tumour and the
      leading cause of cancer-related mortality worldwide. Clarification of the
      mechanism that underlies CRC tumorigenesis and progression therefore is urgently
      needed ffor developing novel therapies. Through analysis of The Cancer Genome
      Atlas (TCGA) dataset, we identified an interesting gene, ZG16, which is
      significantly decreased in CRC samples compared to adjacent non-tumor tissues and
      associated with prognosis of patients. We found that the expression of ZG16
      correlated with CRC related genes which were regulated by APC/CTNNB1 pathway.
      Interestingly, the expression of ZG16 was negatively correlated with CRC stem
      cell marker, LGR5. Overexpression of ZG16 significantly inhibits growth and
      sphere formation of stem-like CRC cells. Moreover, we also identified an upstream
      regulator of ZG16, miR-196a, which was significantly overexpressed in CRC and
      promotes cell growth and stemness. In conclusion, this study demonstrated that
      loss of ZG16 is regulated by miR-196a and contributes to stemness and progression
      of CRC, which may provide a promising therapeutic strategy for advanced CRCs.

PMID- 27880729
TI  - LMO2 promotes tumor cell invasion and metastasis in basal-type breast cancer by
      altering actin cytoskeleton remodeling.
AB  - LMO2 is traditionally recognized as a pivotal transcriptional regulator during
      embryonic hematopoiesis and angionenesis, and its ectopic expression in T
      lymphocyte progenitors is closely correlated to the onset of acute T lymphocytic
      leukemia. However, recently studies revealed complicated expression features and
      dual functions of LMO2 on tumor behaviors in a variety of cancer types, including
      breast cancers. Basal-type breast cancer is one of the breast cancer subtypes and
      a prognostically unfavorable subtype among all breast cancers. Herein we found
      that in basal-type breast cancer specifically, high LMO2 expression was
      positively correlated with lymph node metastases in patients, promoted tumor cell
      migration and invasion and increased distant metastasis in SCID mice. Moreover,
      the novel function of LMO2 was achieved by its predominantly cytoplasmic location
      and interaction with cofilin1, which is a critical regulator in actin
      cytoskeleton dynamics. These findings suggest a subtype-dependent role of LMO2 in
      breast cancers and the potential of LMO2 as a subtype-specific biomarker for
      clinical practice.

PMID- 27880731
TI  - Smad4 in T cells plays a protective role in the development of autoimmune
      Sjogren's syndrome in the nonobese diabetic mouse.
AB  - We investigated the role of Smad4, a signaling molecule of the TGF-beta pathway,
      in T cells on the pathology of Sjogren's syndrome (SS) in nonobese diabetic (NOD)
      mice, an animal model of SS. T cell-specific Smad4-deleted (Smad4fl/fl,CD4-Cre;
      Smad4 tKO) NOD mice had accelerated development of SS compared with wild-type
      (Smad4+/+,CD4-Cre; WT) NOD mice, including increased lymphocyte infiltration into
      exocrine glands, decreased tear and saliva production, and increased levels of
      autoantibodies at 12 weeks of age. Activated/memory T cells and cytokine (IFN
      gamma, IL-17)-producing T cells were increased in Smad4 tKO NOD mice, however the
      proportion and function of regulatory T (Treg) cells were not different between
      Smad4 tKO and WT NOD mice. Effector T (Teff) cells from Smad4 tKO NOD mice were
      less sensitive than WT Teff cells to suppression by Treg cells. Th17
      differentiation capability of Teff cells was similar between Smad4 tKO and WT NOD
      mice, but IL-17 expression was increased under inducible Treg skewing conditions
      in T cells from Smad4 tKO NOD mice. Our results demonstrate that disruption of
      the Smad4 pathway in T cells of NOD mice increases Teff cell activation resulting
      in upregulation of Th17 cells, indicating that Smad4 in T cells has a protective
      role in the development of SS in NOD mice.

PMID- 27880733
TI  - An automated workflow for patient-specific quality control of contour
      propagation.
AB  - Contour propagation is an essential component of adaptive radiotherapy, but
      current contour propagation algorithms are not yet sufficiently accurate to be
      used without manual supervision. Manual review of propagated contours is time
      consuming, making routine implementation of real-time adaptive radiotherapy
      unrealistic. Automated methods of monitoring the performance of contour
      propagation algorithms are therefore required. We have developed an automated
      workflow for patient-specific quality control of contour propagation and
      validated it on a cohort of head and neck patients, on which parotids were
      outlined by two observers. Two types of error were simulated-mislabelling of
      contours and introducing noise in the scans before propagation. The ability of
      the workflow to correctly predict the occurrence of errors was tested, taking
      both sets of observer contours as ground truth, using receiver operator
      characteristic analysis. The area under the curve was 0.90 and 0.85 for the
      observers, indicating good ability to predict the occurrence of errors. This tool
      could potentially be used to identify propagated contours that are likely to be
      incorrect, acting as a flag for manual review of these contours. This would make
      contour propagation more efficient, facilitating the routine implementation of
      adaptive radiotherapy.

PMID- 27880735
TI  - Automatic 3D liver segmentation based on deep learning and globally optimized
      surface evolution.
AB  - The detection and delineation of the liver from abdominal 3D computed tomography
      (CT) images are fundamental tasks in computer-assisted liver surgery planning.
      However, automatic and accurate segmentation, especially liver detection, remains
      challenging due to complex backgrounds, ambiguous boundaries, heterogeneous
      appearances and highly varied shapes of the liver. To address these difficulties,
      we propose an automatic segmentation framework based on 3D convolutional neural
      network (CNN) and globally optimized surface evolution. First, a deep 3D CNN is
      trained to learn a subject-specific probability map of the liver, which gives the
      initial surface and acts as a shape prior in the following segmentation step.
      Then, both global and local appearance information from the prior segmentation
      are adaptively incorporated into a segmentation model, which is globally
      optimized in a surface evolution way. The proposed method has been validated on
      42 CT images from the public Sliver07 database and local hospitals. On the
      Sliver07 online testing set, the proposed method can achieve an overall score of
      [Formula: see text], yielding a mean Dice similarity coefficient of [Formula: see
      text], and an average symmetric surface distance of [Formula: see text] mm. The
      quantitative validations and comparisons show that the proposed method is
      accurate and effective for clinical application.

PMID- 27880732
TI  - Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy
      and induces ER stress to suppress myeloid-derived suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSCs) are immune suppressive cells that are
      hallmarks of human cancer. MDSCs inhibit cytotoxic T lymphocytes (CTLs) and NK
      cell functions to promote tumor immune escape and progression, and therefore are
      considered key targets in cancer immunotherapy. Recent studies determined a key
      role of the apoptosis pathways in tumor-induced MDSC homeostasis and it is known
      that ceramide plays a key role in regulation of mammalian cell apoptosis. In this
      study, we aimed to determine the efficacy and underlying molecular mechanism of
      ceramide in suppression of MDSCs. Treatment of tumor-bearing mice with LCL521, a
      lysosomotropic inhibitor of acid ceramidase, significantly decreased MDSC
      accumulation in vivo. Using a MDSC-like myeloid cell model, we determined that
      LCL521 targets lysosomes and increases total cellular C16 ceramide level.
      Although MDSC-like cells have functional apoptosis pathways, LCL521-induced MDSC
      death occurs in an apoptosis- and necroptosis-independent mechanism. LCL521
      treatment resulted in an increase in the number of autophagic vesicles,
      heterolysosomes and swollen ERs. Finally, concomitant inhibition of cathepsin B
      and cathepsin D was required to significantly decrease LCL521-induced cell death.
      Our observations indicate that LCL521 targets lysosomes to activate cathepsin B
      and cathepsin D, resulting in interrupted autophagy and ER stress that culminates
      in MDSC death. Therefore, a ceramidase inhibitor is potentially an effective
      adjunct therapeutic agent for suppression of MDSCs to enhance the efficacy of CTL
      based cancer immunotherapy.

PMID- 27880736
TI  - Experimental validation of a multi-energy x-ray adapted scatter separation
      method.
AB  - Both in radiography and computed tomography (CT), recently emerged energy
      resolved x-ray photon counting detectors enable the identification and
      quantification of individual materials comprising the inspected object. However,
      the approaches used for these operations require highly accurate x-ray images.
      The accuracy of the images is severely compromised by the presence of scattered
      radiation, which leads to a loss of spatial contrast and, more importantly, a
      bias in radiographic material imaging and artefacts in CT. The aim of the present
      study was to experimentally evaluate a recently introduced partial attenuation
      spectral scatter separation approach (PASSSA) adapted for multi-energy imaging.
      For this purpose, a prototype x-ray system was used. Several radiographic
      acquisitions of an anthropomorphic thorax phantom were performed. Reference
      primary images were obtained via the beam-stop (BS) approach. The attenuation
      images acquired from PASSSA-corrected data showed a substantial increase in local
      contrast and internal structure contour visibility when compared to uncorrected
      images. A substantial reduction of scatter induced bias was also achieved.
      Quantitatively, the developed method proved to be in relatively good agreement
      with the BS data. The application of the proposed scatter correction technique
      lowered the initial normalized root-mean-square error (NRMSE) of 45% between the
      uncorrected total and the reference primary spectral images by a factor of 9,
      thus reducing it to around 5%.

PMID- 27880737
TI  - Development and clinical introduction of automated radiotherapy treatment
      planning for prostate cancer.
AB  - To develop an automated radiotherapy treatment planning and optimization workflow
      to efficiently create patient specifically optimized clinical grade treatment
      plans for prostate cancer and to implement it in clinical practice. A two-phased
      planning and optimization workflow was developed to automatically generate 77Gy 5
      field simultaneously integrated boost intensity modulated radiation therapy (SIB
      IMRT) plans for prostate cancer treatment. A retrospective planning study (n  = 
      100) was performed in which automatically and manually generated treatment plans
      were compared. A clinical pilot (n  =  21) was performed to investigate the
      usability of our method. Operator time for the planning process was reduced to 
      <5 min. The retrospective planning study showed that 98 plans met all clinical
      constraints. Significant improvements were made in the volume receiving 72Gy
      (V72Gy) for the bladder and rectum and the mean dose of the bladder and the body.
      A reduced plan variance was observed. During the clinical pilot 20 automatically
      generated plans met all constraints and 17 plans were selected for treatment. The
      automated radiotherapy treatment planning and optimization workflow is capable of
      efficiently generating patient specifically optimized and improved clinical grade
      plans. It has now been adopted as the current standard workflow in our clinic to
      generate treatment plans for prostate cancer.

PMID- 27880734
TI  - The role of necrosis, acute hypoxia and chronic hypoxia in 18F-FMISO PET image
      contrast: a computational modelling study.
AB  - Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) is a
      promising technique for imaging tumour hypoxia, and a potential target for
      radiotherapy dose-painting. However, the relationship between FMISO uptake and
      oxygen partial pressure ([Formula: see text]) is yet to be quantified fully.
      Tissue oxygenation varies over distances much smaller than clinical PET
      resolution (<100 MUm versus  ~4 mm), and cyclic variations in tumour perfusion
      have been observed on timescales shorter than typical FMISO PET studies (~20 min
      versus a few hours). Furthermore, tracer uptake may be decreased in voxels
      containing some degree of necrosis. This work develops a computational model of
      FMISO uptake in millimetre-scale tumour regions. Coupled partial differential
      equations govern the evolution of oxygen and FMISO distributions, and a dynamic
      vascular source map represents temporal variations in perfusion. Local FMISO
      binding capacity is modulated by the necrotic fraction. Outputs include
      spatiotemporal maps of [Formula: see text] and tracer accumulation, enabling
      calculation of tissue-to-blood ratios (TBRs) and time-activity curves (TACs) as a
      function of mean tissue oxygenation. The model is characterised using
      experimental data, finding half-maximal FMISO binding at local [Formula: see
      text] of 1.4 mmHg (95% CI: 0.3-2.6 mmHg) and half-maximal necrosis at 1.2 mmHg
      (0.1-4.9 mmHg). Simulations predict a non-linear non-monotonic relationship
      between FMISO activity (4 hr post-injection) and mean tissue [Formula: see text]
      : tracer uptake rises sharply from negligible levels in avascular tissue, peaking
      at  ~5 mmHg and declining towards blood activity in well-oxygenated conditions.
      Greater temporal variation in perfusion increases peak TBRs (range 2.20-5.27) as
      a result of smaller predicted necrotic fraction, rather than fundamental
      differences in FMISO accumulation under acute hypoxia. Identical late FMISO
      uptake can occur in regions with differing [Formula: see text] and necrotic
      fraction, but simulated TACs indicate that additional early-phase information may
      allow discrimination of hypoxic and necrotic signals. We conclude that a robust
      approach to FMISO interpretation (and dose-painting prescription) is likely to be
      based on dynamic PET analysis.

PMID- 27880739
TI  - Estimation of cardiac motion in cine-MRI sequences by correlation transform
      optical flow of monogenic features distance.
AB  - Cine-MRI is widely used for the analysis of cardiac function in clinical routine,
      because of its high soft tissue contrast and relatively short acquisition time in
      comparison with other cardiac MRI techniques. The gray level distribution in
      cardiac cine-MRI is relatively homogenous within the myocardium, and can
      therefore make motion quantification difficult. To ensure that the motion
      estimation problem is well posed, more image features have to be considered. This
      work is inspired by a method previously developed for color image processing. The
      monogenic signal provides a framework to estimate the local phase, orientation,
      and amplitude, of an image, three features which locally characterize the 2D
      intensity profile. The independent monogenic features are combined into a 3D
      matrix for motion estimation. To improve motion estimation accuracy, we chose the
      zero-mean normalized cross-correlation as a matching measure, and implemented a
      bilateral filter for denoising and edge-preservation. The monogenic features
      distance is used in lieu of the color space distance in the bilateral filter.
      Results obtained from four realistic simulated sequences outperformed two other
      state of the art methods even in the presence of noise. The motion estimation
      errors (end point error) using our proposed method were reduced by about 20% in
      comparison with those obtained by the other tested methods. The new methodology
      was evaluated on four clinical sequences from patients presenting with cardiac
      motion dysfunctions and one healthy volunteer. The derived strain fields were
      analyzed favorably in their ability to identify myocardial regions with impaired
      motion.

PMID- 27880740
TI  - Beam angle selection incorporation of anatomical heterogeneities for pencil beam
      scanning charged-particle therapy.
AB  - In charged particle therapy with pencil beam scanning (PBS), localization of the
      dose in the Bragg peak makes dose distributions sensitive to lateral tissue
      heterogeneities. The sensitivity of a PBS plan to lateral tissue heterogeneities
      can be reduced by selecting appropriate beam angles. The purpose of this study is
      to develop a fast and accurate method of beam angle selection for PBS. The
      lateral tissue heterogeneity surrounding the path of the pencil beams at a given
      angle was quantified with the heterogeneity number representing the variation of
      the Bragg peak depth across the cross section of the beams using the stopping
      power ratio of body tissues with respect to water. To shorten the computation
      time, one-dimensional dose optimization was conducted along the central axis of
      the pencil beams as they were directed by the scanning magnets. The heterogeneity
      numbers were derived for all possible beam angles for treatment. The angles
      leading to the minimum mean heterogeneity number were selected as the optimal
      beam angle. Three clinical cases of head and neck cancer were used to evaluate
      the developed method. Dose distributions and their robustness to setup and range
      errors were evaluated for all tested angles, and their relation to the
      heterogeneity numbers was investigated. The mean heterogeneity number varied from
      1.2 mm-10.6 mm in the evaluated cases. By selecting a field with a low mean
      heterogeneity number, target dose coverage and robustness against setup and range
      errors were improved. The developed method is simple, fast, accurate and
      applicable for beam angle selection in charged particle therapy with PBS.

PMID- 27880738
TI  - An adaptive reconstruction algorithm for spectral CT regularized by a reference
      image.
AB  - The photon counting detector based spectral CT system is attracting increasing
      attention in the CT field. However, the spectral CT is still premature in terms
      of both hardware and software. To reconstruct high quality spectral images from
      low-dose projections, an adaptive image reconstruction algorithm is proposed that
      assumes a known reference image (RI). The idea is motivated by the fact that the
      reconstructed images from different spectral channels are highly correlated. If a
      high quality image of the same object is known, it can be used to improve the low
      dose reconstruction of each individual channel. This is implemented by maximizing
      the patch-wise correlation between the object image and the RI. Extensive
      numerical simulations and preclinical mouse study demonstrate the feasibility and
      merits of the proposed algorithm. It also performs well for truncated local
      projections, and the surrounding area of the region- of-interest (ROI) can be
      more accurately reconstructed. Furthermore, a method is introduced to adaptively
      choose the step length, making the algorithm more feasible and easier for
      applications.

PMID- 27880742
TI  - Probiotic Administration in Infants With Gastroschisis: A Pilot Randomized
      Placebo-Controlled Trial.

PMID- 27880741
TI  - OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CHORIORETINAL LESIONS DUE TO
      IDIOPATHIC MULTIFOCAL CHOROIDITIS.
AB  - PURPOSE: To evaluate the spectrum of macular chorioretinal lesions occurring in
      idiopathic multifocal choroiditis using optical coherence tomography angiography
      (OCTA) to evaluate those showing neovascular flow. METHODS: This was a
      descriptive, retrospective study of 18 eyes of 14 patients with multifocal
      choroiditis. Macular lesions were characterized as subretinal pigment epithelium,
      subretinal, or mixed and evaluated during active and presumed inactive states of
      multifocal choroiditis. Correlations between structural optical coherence
      tomography and OCTA were performed. In select cases, correlations between OCTA,
      fluorescein angiography, and fundus autofluorescence were evaluated. In 5 eyes,
      quantitative measurements of neovascular lesions were compared at baseline and
      following intravitreal anti-vascular endothelial growth factor therapy. RESULTS:
      Mean patient age was 48 years (SD: 13.8; 86% women). Optical coherence tomography
      angiography flow signatures consistent with neovascularization were identified in
      83% of eyes, including in 0% of subretinal pigment epithelium, 91% of subretinal,
      and 100% of mixed lesions. Lesions that did not demonstrate definitive signs of
      fluorescein angiography leakage were frequently found to have neovascularization
      using OCTA. There was no change in quantitative measurements of neovascular
      lesions after anti-vascular endothelial growth factor therapy (all tested
      variables P > 0.05). CONCLUSION: Optical coherence tomography angiography may be
      a useful imaging modality for understanding the pathophysiology of multifocal
      choroiditis and monitoring its clinical course.

PMID- 27880744
TI  - Notice to Readers: Final 2015 Reports of Nationally Notifiable Infectious
      Diseases and Conditions.
AB  - The table listed in this report on pages 1307-1321 presents finalized data, as of
      June 30, 2016, from the National Notifiable Diseases Surveillance System (NNDSS)
      for 2015. These data will be published in more detail in the Summary of
      Notifiable Infectious Diseases and Conditions - United States, 2015 (1). Because
      no cases were reported in the United States during 2015, the following diseases
      do not appear in this early release table: anthrax; dengue hemorrhagic fever;
      diphtheria; eastern equine encephalitis virus disease, nonneuroinvasive;
      poliomyelitis, paralytic; poliovirus infection, nonparalytic; severe acute
      respiratory syndrome-associated coronavirus disease (SARS-CoV); smallpox; western
      equine encephalitis virus disease, neuroinvasive and nonneuroinvasive; yellow
      fever; and viral hemorrhagic fevers.

PMID- 27880743
TI  - Ras-Association Domain Family 1 Isoform A (RASSF1A) Gene Polymorphism rs1989839
      is Associated with Risk and Metastatic Potential of Osteosarcoma in Young Chinese
      Individuals: A Multi-Center, Case-Control Study.
AB  - BACKGROUND The ras-association domain family 1 isoform A (RASSF1A) gene serves as
      a bona fide tumor suppressor gene. The polymorphisms in RASSF1A were previously
      reported to be associated with the risk of solid malignant tumors. We
      hypothesized herein that RASSF1A gene polymorphisms are involved in the risk and
      prognosis of osteosarcoma (OS). MATERIAL AND METHODS We recruited 279 young OS
      cases and 286 tumor-free controls from the east Chinese population. Five tagSNPs
      of RASSF1A gene (rs2236947A/C, rs2073497A/C, rs1989839C/T, rs72932987C/T, and
      rs4688728G/T) were genotyped. DNA was isolated from blood samples and then
      underwent PCR analysis for genotyping. RESULTS rs1989839C/T is an important
      predictor of osteosarcoma risk and outcome. The CT genotype of rs1989839 is
      highly related to elevated risk of osteosarcoma. Furthermore, rs1989839C/T is
      also associated with the Enneking stage of osteosarcoma and risk of lung
      metastasis. One of the other 4 SNPs, rs2236947A/C, shows a borderline
      significance in predicting osteosarcoma risk. CONCLUSIONS Our study is the first
      to prove that RASSF1A gene polymorphisms may potentially be predictive for
      osteosarcoma risk and prognosis.

PMID- 27880745
TI  - Announcement: National Family History Day - November 24, 2016.
AB  - In 2004, the U.S. Surgeon General declared that Thanksgiving would be National
      Family History Day, a day designed to encourage American families to learn about
      and create a written record of their family health history. Family history can
      identify those persons with a higher-than-average risk for many common diseases,
      such as heart disease, cancer, and type 2 diabetes. Having at least one first
      degree relative with a disease can increase a person's risk twofold or more (1).
      Family history is also a determinant of less common diseases like sickle cell
      disease and cystic fibrosis (1). Persons who might be at increased risk because
      of family history might benefit from screening or other interventions to prevent
      disease or detect it earlier.

PMID- 27880746
TI  - Notice to Readers: NNDSS Tables Have Updated "N" Indicators for 2015 and 2016.
AB  - CDC's National Notifiable Diseases Surveillance System (NNDSS) maintains and
      annually updates information about whether each Nationally Notifiable Infectious
      Condition (NNIC) is considered "reportable" (by health care providers, hospitals,
      laboratories, or other public health reporters) in each reporting jurisdiction.
      NNDSS personnel within the Division of Health Informatics and Surveillance
      performed assessments with each reporting jurisdiction to ascertain the
      reportable disease status of each NNIC for 2015 and 2016. NNICs that are not
      designated reportable are indicated with an "N"; NNICs that are reportable, but
      for which no cases were reported, are indicated with a "-" and NNICs that are
      reportable, but for which data are not available in a jurisdiction, are
      designated by either "U" or "NA." These designations are used in the annual MMWR
      Summary of Notifiable Diseases - United States and in the weekly MMWR Notifiable
      Diseases and Mortality Tables I and II of provisional NNDSS data.

PMID- 27880747
TI  - Announcement: Guidance for U.S. Laboratory Testing for Zika Virus Infection:
      Implications for Health Care Providers.
AB  - CDC has released updated guidance online for U.S. laboratory testing for Zika
      virus infection. The guidance is available at
      https://www.cdc.gov/zika/laboratories/lab-guidance.html. Frequently asked
      questions are addressed at https://www.cdc.gov/zika/laboratories/lab-guidance
      faq.html. This guidance updates recommendations for testing of specimens by U.S.
      laboratories for possible Zika virus infection. Major updates to the guidance
      with clinical implications for health care providers include the following.

PMID- 27880748
TI  - CDC Grand Rounds: Family History and Genomics as Tools for Cancer Prevention and
      Control.
AB  - Although many efforts in cancer prevention and control have routinely focused on
      behavioral risk factors, such as tobacco use, or on the early detection of
      cancer, such as colorectal cancer screening, advances in genetic testing have
      created new opportunities for cancer prevention through evaluation of family
      history and identification of cancer-causing inherited mutations. Through the
      collection and evaluation of a family cancer history by a trained health care
      provider, patients and families at increased risk for a hereditary cancer
      syndrome can be identified, referred for genetic counseling and testing, and make
      informed decisions about options for cancer risk reduction (1). Although
      hereditary cancers make up a small proportion of all cancers, the number of
      affected persons can be large, and the level of risk among affected persons is
      high. Two hereditary cancer syndromes for which public health professionals have
      worked to reduce the burden of morbidity and mortality are hereditary breast and
      ovarian cancer syndrome (HBOC) and Lynch syndrome.

PMID- 27880749
TI  - Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan
      African Countries, 2011-2015.
AB  - Pediatric human immunodeficiency virus (HIV) infection remains an important
      public health issue in resource-limited settings. In 2015, 1.4 million children
      aged <15 years were estimated to be living with HIV (including 170,000 infants
      born in 2015), with the vast majority living in sub-Saharan Africa (1). In 2014,
      150,000 children died from HIV-related causes worldwide (2). Access to timely HIV
      diagnosis and treatment for HIV-infected infants reduces HIV-associated
      mortality, which is approximately 50% by age 2 years without treatment (3). Since
      2011, the annual number of HIV-infected children has declined by 50%. Despite
      this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test
      for HIV (2), and in 2015, only 51% of children living with HIV received
      antiretroviral therapy (1). Access to services for early infant diagnosis of HIV
      (which includes access to testing for HIV-exposed infants and clinical diagnosis
      of HIV-infected infants) is critical for reducing HIV-associated mortality in
      children aged <15 years. Using data collected from seven countries supported by
      the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the
      provision of HIV testing services for early infant diagnosis was assessed. During
      2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed
      infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as
      recommended by the World Health Organization (WHO) increased in all seven
      countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi,
      South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for
      early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV
      positivity among those tested declined in all seven countries, with three
      countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda)
      reporting >50% decline. The most common challenges for access to testing for
      early infant diagnosis included difficulties in specimen transport, long
      turnaround time between specimen collection and receipt of results, and
      limitations in supply chain management. Further reductions in HIV mortality in
      children can be achieved through continued expansion and improvement of services
      for early infant diagnosis in PEPFAR-supported countries, including initiatives
      targeted to reach HIV-exposed infants, ensure access to programs for early infant
      diagnosis of HIV, and facilitate prompt linkage to treatment for children
      diagnosed with HIV infection.

PMID- 27880751
TI  - Abortion Surveillance - United States, 2013.
AB  - PROBLEM/CONDITION: Since 1969, CDC has conducted abortion surveillance to
      document the number and characteristics of women obtaining legal induced
      abortions in the United States. PERIOD COVERED: 2013. DESCRIPTION OF SYSTEM: Each
      year, CDC requests abortion data from the central health agencies of 52 reporting
      areas (the 50 states, the District of Columbia, and New York City). The reporting
      areas provide this information voluntarily. For 2013, data were received from 49
      reporting areas. For trend analysis, abortion data were evaluated from 47 areas
      that reported data every year during 2004-2013. Census and natality data,
      respectively, were used to calculate abortion rates (number of abortions per
      1,000 women) and ratios (number of abortions per 1,000 live births). RESULTS: A
      total of 664,435 abortions were reported to CDC for 2013. Of these abortions,
      98.2% were from the 47 reporting areas that provided data every year during 2004
      2013. Among these 47 reporting areas, the abortion rate for 2013 was 12.5
      abortions per 1,000 women aged 15-44 years, and the abortion ratio was 200
      abortions per 1,000 live births. From 2012 to 2013, the total number, rate, and
      ratio of reported abortions decreased 5%. From 2004 to 2013, the total number,
      rate, and ratio of reported abortions decreased 20%, 21%, and 17%, respectively.
      In 2013, all three measures reached their lowest level for the entire period of
      analysis (2004-2013). In 2013 and throughout the period of analysis, women in
      their 20s accounted for the majority of abortions and had the highest abortion
      rates; women in their 30s and older accounted for a much smaller percentage of
      abortions and had lower abortion rates. In 2013, women aged 20-24 and 25-29 years
      accounted for 32.7% and 25.9% of all abortions, respectively, and had abortion
      rates of 21.8 and 18.2 abortions per 1,000 women aged 20-24 and 25-29 years,
      respectively. In contrast, women aged 30-34, 35-39, and >=40 years accounted for
      16.8%, 9.2%, and 3.6% of all abortions, respectively, and had abortion rates of
      11.8, 7.0, and 2.5 abortions per 1,000 women aged 30-34 years, 35-39 years, and
      >=40 years, respectively. During 2004-2013, the decrease in abortion rates among
      adult women aged 20-39 years ranged from 8% to 27% across these age groups,
      whereas the abortion rate was stable for women aged >=40 years. In 2013,
      adolescents aged <15 and 15-19 years accounted for 0.3% and 11.4% of all
      abortions, respectively, and had abortion rates of 0.6 and 8.2 abortions per
      1,000 adolescents aged <15 and 15-19 years, respectively. From 2004 to 2013, the
      percentage of abortions accounted for by adolescents aged 15-19 years decreased
      31% and their abortion rate decreased 46%. These decreases were greater than the
      decreases for women in any older age group. In contrast to the percentage
      distribution of abortions and abortion rates by age, abortion ratios in 2013 and
      throughout the entire period of analysis were highest among adolescents and
      lowest among women aged 30-39 years. Abortion ratios decreased from 2004 to 2013
      for women in all age groups, except for adolescents aged <15 years. In 2013, the
      majority (66.0%) of abortions were performed by <=8 weeks' gestation, and nearly
      all (91.6%) were performed by <=13 weeks' gestation. Few abortions were performed
      between 14 and 20 weeks' gestation (7.1%) or at >=21 weeks' gestation (1.3%).
      From 2004 to 2013, the percentage of all abortions performed at <=13 weeks'
      gestation remained consistently high (>=91.5%) and among those performed at <=13
      weeks' gestation, the percentage performed at <=6 weeks' gestation increased 16%.
      In 2013, among the 43 reporting areas that included medical (nonsurgical)
      abortion on their reporting form, a total of 67.9% of abortions were performed by
      curettage at <=13 weeks' gestation, 22.2% were performed by early medical
      abortion (a nonsurgical abortion at <=8 weeks' gestation), and 8.6% were
      performed by curettage at >13 weeks' gestation; all other methods were uncommon.
      Among abortions performed at <=8 weeks' gestation that were eligible for early
      medical abortion on the basis of gestational age, 32.8% were completed by this
      method. From 2012 to 2013, the percentage of abortions reported as early medical
      abortions increased 5%. Deaths of women associated with complications from
      abortion for 2013 are being investigated as part of CDC's Pregnancy Mortality
      Surveillance System. In 2012, the most recent year for which data were available,
      four women were identified to have died as a result of complications from known
      legal induced abortion. No reported deaths were associated with known illegal
      induced abortion. INTERPRETATION: Among the 47 areas that reported data every
      year during 2004-2013, the decreases in the total number, rate, and ratio of
      reported abortions that occurred during 2009-2012 continued from 2012 to 2013,
      resulting in historic lows for all three measures of abortion. PUBLIC HEALTH
      ACTION: The data in this report can help program planners and policymakers
      identify groups of women with highest rates of abortion. Unintended pregnancy is
      the major contributor to abortion. Increasing access to and use of contraception,
      including the most effective methods, can reduce unintended pregnancies and
      further reduce the number of abortions performed in the United States.

PMID- 27880750
TI  - Notes from the Field: Clostridium perfringens Gastroenteritis Outbreak Associated
      with a Catered Lunch - North Carolina, November 2015.
AB  - During November 2015, the North Carolina Division of Public Health was notified
      by the Pitt County Health Department (PCHD) that approximately 40 persons who
      attended a catered company Thanksgiving lunch the previous day were ill with
      diarrhea and abdominal pain. The North Carolina Division of Public Health and
      PCHD worked together to investigate the source of illness and implement control
      measures. Within hours of notification, investigators developed and distributed
      an online survey to all lunch attendees regarding symptoms and foods consumed and
      initiated a cohort study. A case of illness was defined as abdominal pain or
      diarrhea in a lunch attendee with illness onset <24 hours after the event. Risk
      ratios (RRs) and 95% confidence intervals (CIs) were estimated for all menu
      items. Among 80 attendees, 58 (73%) completed the survey, including 44
      respondents (76%) who reported illnesses meeting the case definition; among
      these, 41 (93%) reported diarrhea, and 40 (91%) reported abdominal pain. There
      were no hospitalizations. Symptom onset began a median of 13 hours after lunch
      (range = 1-22 hours). Risk for illness among persons who ate turkey or stuffing
      (38 of 44; 86%), which were plated and served together, was significantly higher
      than risk for illness among those who did not eat turkey or stuffing (six of 14;
      43%) (RR = 2.02; 95% CI = 1.09-3.73).

PMID- 27880752
TI  - Progress Toward Poliomyelitis Eradication - Pakistan, January 2015-September
      2016.
AB  - Pakistan, Afghanistan, and Nigeria remain the only countries where endemic wild
      poliovirus type 1 (WPV1) transmission continues. This report describes the
      activities, challenges, and progress toward polio eradication in Pakistan during
      January 2015-September 2016 and updates previous reports (1,2). In 2015, a total
      of 54 WPV1 cases were reported in Pakistan, an 82% decrease from 2014. In 2016,
      15 WPV1 cases had been reported as of November 1, representing a 61% decrease
      compared with the 38 cases reported during the same period in 2015 (Figure 1).
      Among the 15 WPV1 cases reported in 2016, children aged <36 months accounted for
      13 cases; four of those children had received only a single dose of oral
      poliovirus vaccine (OPV). Seven of the 15 WPV1 cases occurred in the province of
      Khyber Pakhtunkhwa (KP), five in Sindh, two in the Federally Administered Tribal
      Areas (FATA), and one in Balochistan (3). During January-September 2016, WPV1 was
      detected in 9% (36 of 384) of environmental samples collected, compared with 19%
      (69 of 354) of samples collected during the same period in 2015. Rigorous
      implementation of the 2015-2016 National Emergency Action Plan (NEAP) (4),
      coordinated by the National Emergency Operations Center (EOC), has resulted in a
      substantial decrease in overall WPV1 circulation compared with the previous year.
      However, detection of WPV1 cases in high-risk areas and the detection of WPV1 in
      environmental samples from geographic areas where no polio cases are identified
      highlight the need to continue to improve the quality of supplemental
      immunization activities (SIAs),* immunization campaigns focused on vaccinating
      children with OPV outside of routine immunization services, and surveillance for
      acute flaccid paralysis (AFP). Continuation and refinement of successful program
      strategies, as outlined in the new 2016-2017 NEAP (5), with particular focus on
      identifying children missed by vaccination, community-based vaccination, and
      rapid response to virus identification are needed to stop WPV transmission.

PMID- 27880753
TI  - Notes from the Field: Community-Based Prevention of Rocky Mountain Spotted Fever 
      Sonora, Mexico, 2016.
AB  - Rocky Mountain spotted fever (RMSF), a life-threatening tickborne zoonosis caused
      by Rickettsia rickettsii, is a reemerging disease in Mexico (1,2). R. rickettsii
      is an intracellular bacterium that infects vascular endothelium and can cause
      multisystem organ failure and death in the absence of timely administration of a
      tetracycline-class antibiotic, typically doxycycline. Epidemic RMSF, as described
      in parts of Arizona and Mexico, is associated with massive local infestations of
      the brown dog tick (Rhiphicephalus sanguineus sensu lato) on domestic dogs and in
      peridomestic settings that result in high rates of human exposure; for example,
      during 2003-2012, in Arizona the incidence of RMSF in the three most highly
      affected communities was 150 times the U.S. national average (3,4). In 2015, the
      Mexico Ministry of Health (MOH) declared an epidemiologic emergency because of
      high and sustained rates of RMSF in several states in northern Mexico, including
      the state of Sonora. During 2004-2015, a total of 1,129 cases and 188 RMSF deaths
      were reported from Sonora (Sonora MOH, unpublished data, 2016). During 2009-2015,
      one impoverished community (community A) in Sonora reported 56 cases of RMSF
      involving children and adolescents, with a case-fatality rate of 40% (Sonora MOH,
      unpublished data, 2016). Poverty and lack of timely access to health services are
      risk factors for severe RMSF. Children are especially vulnerable to infection,
      because they might have increased contact with dogs and spend more time playing
      around spaces where ticks survive (5). In Sonora, case fatality rates for
      children aged <10 years can be as high as 30%, which is almost four times the
      aggregate case-fatality rate reported for the general population of the state
      (8%) (2), and 10-13 times higher than the case-fatality rate described for this
      age group in the United States (2.4%) (6).

PMID- 27880754
TI  - QuickStats: Percentage* of Adults Aged >=20 Years Who Ever Told A Doctor That
      They Had Trouble Sleeping,? by Age Group and Sex - National Health and Nutrition
      Examination Survey, 2013-2014.
AB  - In 2013-2014, 28.0% of U.S. adults reported that they had told a doctor or other
      health professional that they had trouble sleeping. A smaller percentage of
      adults aged 20-39 years (19.2%) reported having trouble sleeping compared with
      persons aged 40-59 years (32.8%) and >=60 years (33.2%). This pattern by age
      group was observed for both men and women, although larger percentages of women
      aged 40-59 years and >=60 years reported trouble sleeping compared with men in
      those age groups.

PMID- 27880756
TI  - Sub-ice-shelf sediments record history of twentieth-century retreat of Pine
      Island Glacier.
AB  - The West Antarctic Ice Sheet is one of the largest potential sources of rising
      sea levels. Over the past 40 years, glaciers flowing into the Amundsen Sea sector
      of the ice sheet have thinned at an accelerating rate, and several numerical
      models suggest that unstable and irreversible retreat of the grounding line-which
      marks the boundary between grounded ice and floating ice shelf-is underway.
      Understanding this recent retreat requires a detailed knowledge of grounding-line
      history, but the locations of the grounding line before the advent of satellite
      monitoring in the 1990s are poorly dated. In particular, a history of grounding
      line retreat is required to understand the relative roles of contemporaneous
      ocean-forced change and of ongoing glacier response to an earlier perturbation in
      driving ice-sheet loss. Here we show that the present thinning and retreat of
      Pine Island Glacier in West Antarctica is part of a climatically forced trend
      that was triggered in the 1940s. Our conclusions arise from analysis of sediment
      cores recovered beneath the floating Pine Island Glacier ice shelf, and constrain
      the date at which the grounding line retreated from a prominent seafloor ridge.
      We find that incursion of marine water beyond the crest of this ridge, forming an
      ocean cavity beneath the ice shelf, occurred in 1945 (+/-12 years); final
      ungrounding of the ice shelf from the ridge occurred in 1970 (+/-4 years). The
      initial opening of this ocean cavity followed a period of strong warming of West
      Antarctica, associated with El Nino activity. Thus our results suggest that, even
      when climate forcing weakened, ice-sheet retreat continued.

PMID- 27880755
TI  - [Spanish Adaptation of the 2016 European Guidelines on Cardiovascular Disease
      Prevention in Clinical Practice].
AB  - The VI European Guidelines for Cardiovascular Prevention recommend combining
      population and high-risk strategies with lifestyle changes as a cornerstone of
      prevention, and propose the SCORE function to quantify cardiovascular risk. The
      guidelines highlight disease specific interventions, and conditions as women,
      young people and ethnic minorities. Screening for subclinical atherosclerosis
      with noninvasive imaging techniques is not recommended. The guidelines
      distinguish four risk levels (very high, high, moderate and low) with therapeutic
      objectives for lipid control according to risk. Diabetes mellitus confers a high
      risk, except for subjects with type 2 diabetes with less than 10 years of
      evolution, without other risk factors or complications, or type 1 diabetes of
      short evolution without complications. The decision to start pharmacological
      treatment of arterial hypertension will depend on the blood pressure level and
      the cardiovascular risk, taking into account the lesion of target organs. The
      guidelines don't recommend antiplatelet drugs in primary prevention because of
      the increased bleeding risk. The low adherence to the medication requires
      simplified therapeutic regimes and to identify and combat its causes. The
      guidelines highlight the responsibility of health professionals to take an active
      role in advocating evidence-based interventions at the population level, and
      propose effective interventions, at individual and population level, to promote a
      healthy diet, the practice of physical activity, the cessation of smoking and the
      protection against alcohol abuse.

PMID- 27880757
TI  - Redefining the invertebrate RNA virosphere.
AB  - Current knowledge of RNA virus biodiversity is both biased and fragmentary,
      reflecting a focus on culturable or disease-causing agents. Here we profile the
      transcriptomes of over 220 invertebrate species sampled across nine animal phyla
      and report the discovery of 1,445 RNA viruses, including some that are
      sufficiently divergent to comprise new families. The identified viruses fill
      major gaps in the RNA virus phylogeny and reveal an evolutionary history that is
      characterized by both host switching and co-divergence. The invertebrate virome
      also reveals remarkable genomic flexibility that includes frequent recombination,
      lateral gene transfer among viruses and hosts, gene gain and loss, and complex
      genomic rearrangements. Together, these data present a view of the RNA virosphere
      that is more phylogenetically and genomically diverse than that depicted in
      current classification schemes and provide a more solid foundation for studies in
      virus ecology and evolution.

PMID- 27880758
TI  - Corrigendum: The Asian monsoon over the past 640,000 years and ice age
      terminations.

PMID- 27880760
TI  - Astronomy: A black hole changes its feeding habits.

PMID- 27880759
TI  - Cell biology: Double agents for mitochondrial division.

PMID- 27880761
TI  - Biological rhythms: Wild times.

PMID- 27880763
TI  - Inhibition of mTOR induces a paused pluripotent state.
AB  - Cultured pluripotent stem cells are a cornerstone of regenerative medicine owing
      to their ability to give rise to all cell types of the body. Although pluripotent
      stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically
      a transient state in vivo, lasting 2-3 days around the time of blastocyst
      implantation. The exception to this rule is embryonic diapause, a reversible
      state of suspended development triggered by unfavourable conditions. Diapause is
      a physiological reproductive strategy widely employed across the animal kingdom,
      including in mammals, but its regulation remains poorly understood. Here we
      report that the partial inhibition of mechanistic target of rapamycin (mTOR), a
      major nutrient sensor and promoter of growth, induces reversible pausing of mouse
      blastocyst development and allows their prolonged culture ex vivo. Paused
      blastocysts remain pluripotent and competent-able to give rise to embryonic stem
      (ES) cells and live, fertile mice. We show that both naturally diapaused
      blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions
      in mTOR activity, translation, histone modifications associated with gene
      activity and transcription. Pausing can be induced directly in cultured ES cells
      and sustained for weeks without appreciable cell death or deviations from cell
      cycle distributions. We show that paused ES cells display a remarkable global
      suppression of transcription, maintain a gene expression signature of diapaused
      blastocysts and remain pluripotent. These results uncover a new pluripotent stem
      cell state corresponding to the epiblast of the diapaused blastocyst and indicate
      that mTOR regulates developmental timing at the peri-implantation stage. Our
      findings have implications in the fields of assisted reproduction, regenerative
      medicine, cancer, metabolic disorders and ageing.

PMID- 27880764
TI  - Malaria Elimination Campaigns in the Lake Kariba Region of Zambia: A Spatial
      Dynamical Model.
AB  - As more regions approach malaria elimination, understanding how different
      interventions interact to reduce transmission becomes critical. The Lake Kariba
      area of Southern Province, Zambia, is part of a multi-country elimination effort
      and presents a particular challenge as it is an interconnected region of variable
      transmission intensities. In 2012-13, six rounds of mass test-and-treat drug
      campaigns were carried out in the Lake Kariba region. A spatial dynamical model
      of malaria transmission in the Lake Kariba area, with transmission and climate
      modeled at the village scale, was calibrated to the 2012-13 prevalence survey
      data, with case management rates, insecticide-treated net usage, and drug
      campaign coverage informed by surveillance. The model captured the spatio
      temporal trends of decline and rebound in malaria prevalence in 2012-13 at the
      village scale. Various interventions implemented between 2016-22 were simulated
      to compare their effects on reducing regional transmission and achieving and
      maintaining elimination through 2030. Simulations predict that elimination
      requires sustaining high coverage with vector control over several years. When
      vector control measures are well-implemented, targeted mass drug campaigns in
      high-burden areas further increase the likelihood of elimination, although drug
      campaigns cannot compensate for insufficient vector control. If infections are
      regularly imported from outside the region into highly receptive areas, vector
      control must be maintained within the region until importations cease.
      Elimination in the Lake Kariba region is possible, although human movement both
      within and from outside the region risk damaging the success of elimination
      programs.

PMID- 27880765
TI  - Mechanisms for Complex Chromosomal Insertions.
AB  - Chromosomal insertions are genomic rearrangements with a chromosome segment
      inserted into a non-homologous chromosome or a non-adjacent locus on the same
      chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number
      gains. Little is known about the molecular mechanisms of their formation. We
      identified 16 individuals with complex insertions among 56,000 individuals tested
      at Baylor Genetics using clinical array comparative genomic hybridization (aCGH)
      and fluorescence in situ hybridization (FISH). Custom high-density aCGH was
      performed on 10 individuals with available DNA, and breakpoint junctions were
      fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6
      individuals to glean insights into potential mechanisms of formation. We observed
      microhomologies and templated insertions at the breakpoint junctions, resembling
      the breakpoint junction signatures found in complex genomic rearrangements
      generated by replication-based mechanism(s) with iterative template switches. In
      addition, we analyzed 5 families with apparently balanced insertion in one parent
      detected by FISH analysis and found that 3 parents had additional small copy
      number variants (CNVs) at one or both sides of the inserting fragments as well as
      at the inserted sites. We propose that replicative repair can result in
      interchromosomal complex insertions generated through chromothripsis-like
      chromoanasynthesis involving two or three chromosomes, and cause a significant
      fraction of apparently balanced insertions harboring small flanking CNVs.

PMID- 27880762
TI  - Unexpected diversity in socially synchronized rhythms of shorebirds.
AB  - The behavioural rhythms of organisms are thought to be under strong selection,
      influenced by the rhythmicity of the environment. Such behavioural rhythms are
      well studied in isolated individuals under laboratory conditions, but free-living
      individuals have to temporally synchronize their activities with those of others,
      including potential mates, competitors, prey and predators. Individuals can
      temporally segregate their daily activities (for example, prey avoiding
      predators, subordinates avoiding dominants) or synchronize their activities (for
      example, group foraging, communal defence, pairs reproducing or caring for
      offspring). The behavioural rhythms that emerge from such social synchronization
      and the underlying evolutionary and ecological drivers that shape them remain
      poorly understood. Here we investigate these rhythms in the context of biparental
      care, a particularly sensitive phase of social synchronization where pair members
      potentially compromise their individual rhythms. Using data from 729 nests of 91
      populations of 32 biparentally incubating shorebird species, where parents
      synchronize to achieve continuous coverage of developing eggs, we report
      remarkable within- and between-species diversity in incubation rhythms. Between
      species, the median length of one parent's incubation bout varied from 1-19 h,
      whereas period length-the time in which a parent's probability to incubate cycles
      once between its highest and lowest value-varied from 6-43 h. The length of
      incubation bouts was unrelated to variables reflecting energetic demands, but
      species relying on crypsis (the ability to avoid detection by other animals) had
      longer incubation bouts than those that are readily visible or who actively
      protect their nest against predators. Rhythms entrainable to the 24-h light-dark
      cycle were less prevalent at high latitudes and absent in 18 species. Our results
      indicate that even under similar environmental conditions and despite 24-h
      environmental cues, social synchronization can generate far more diverse
      behavioural rhythms than expected from studies of individuals in captivity. The
      risk of predation, not the risk of starvation, may be a key factor underlying the
      diversity in these rhythms.

PMID- 27880768
TI  - Real-Time Control of an Articulatory-Based Speech Synthesizer for Brain Computer
      Interfaces.
AB  - Restoring natural speech in paralyzed and aphasic people could be achieved using
      a Brain-Computer Interface (BCI) controlling a speech synthesizer in real-time.
      To reach this goal, a prerequisite is to develop a speech synthesizer producing
      intelligible speech in real-time with a reasonable number of control parameters.
      We present here an articulatory-based speech synthesizer that can be controlled
      in real-time for future BCI applications. This synthesizer converts movements of
      the main speech articulators (tongue, jaw, velum, and lips) into intelligible
      speech. The articulatory-to-acoustic mapping is performed using a deep neural
      network (DNN) trained on electromagnetic articulography (EMA) data recorded on a
      reference speaker synchronously with the produced speech signal. This DNN is then
      used in both offline and online modes to map the position of sensors glued on
      different speech articulators into acoustic parameters that are further converted
      into an audio signal using a vocoder. In offline mode, highly intelligible speech
      could be obtained as assessed by perceptual evaluation performed by 12 listeners.
      Then, to anticipate future BCI applications, we further assessed the real-time
      control of the synthesizer by both the reference speaker and new speakers, in a
      closed-loop paradigm using EMA data recorded in real time. A short calibration
      period was used to compensate for differences in sensor positions and
      articulatory differences between new speakers and the reference speaker. We found
      that real-time synthesis of vowels and consonants was possible with good
      intelligibility. In conclusion, these results open to future speech BCI
      applications using such articulatory-based speech synthesizer.

PMID- 27880766
TI  - SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell
      Injury State during Lung Squamous Cell Carcinoma Pathogenesis.
AB  - Although cancers are considered stem cell diseases, mechanisms involving stem
      cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the
      second most common lung cancer, and its pathogenesis appears to hinge on changes
      in the stem cell behavior of basal cells in the bronchial airways. Basal cells
      are normally quiescent and differentiate into mucociliary epithelia. Smoking
      triggers a hyperproliferative response resulting in progressive premalignant
      epithelial changes ranging from squamous metaplasia to dysplasia. These changes
      can regress naturally, even with chronic smoking. However, for unknown reasons,
      dysplasias have higher progression rates than earlier stages. We used primary
      human tracheobronchial basal cells to investigate how copy number gains in SOX2
      and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of
      SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling,
      which is activated by smoking, to initiate the squamous injury response in basal
      cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K
      signaling levels are high during dysplasia, while SOX9 is not expressed. By
      contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and
      basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting
      proliferation and preventing squamous differentiation. Transient reduction in
      SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and
      drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification
      of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal
      cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the
      squamous injury response while precluding normal mucociliary differentiation.
      Surprisingly, we find that, although later in invasive carcinoma SOX9 is
      generally expressed at low levels, its expression is higher in a subset of SQCCs
      with less squamous identity and worse clinical outcome. We propose that early
      pathogenesis of most SQCCs involves stabilization of the squamous injury state in
      stem cells through copy number gains at 3q, with the pro-proliferative activity
      of SOX9 possibly being exploited in a subset of SQCCs in later stages.

PMID- 27880767
TI  - Distribution of Misfolded Prion Protein Seeding Activity Alone Does Not Predict
      Regions of Neurodegeneration.
AB  - Protein misfolding is common across many neurodegenerative diseases, with
      misfolded proteins acting as seeds for "prion-like" conversion of normally folded
      protein to abnormal conformations. A central hypothesis is that misfolded protein
      accumulation, spread, and distribution are restricted to specific neuronal
      populations of the central nervous system and thus predict regions of
      neurodegeneration. We examined this hypothesis using a highly sensitive assay
      system for detection of misfolded protein seeds in a murine model of prion
      disease. Misfolded prion protein (PrP) seeds were observed widespread throughout
      the brain, accumulating in all brain regions examined irrespective of
      neurodegeneration. Importantly, neither time of exposure nor amount of misfolded
      protein seeds present determined regions of neurodegeneration. We further
      demonstrate two distinct microglia responses in prion-infected brains: a novel
      homeostatic response in all regions and an innate immune response restricted to
      sites of neurodegeneration. Therefore, accumulation of misfolded prion protein
      alone does not define targeting of neurodegeneration, which instead results only
      when misfolded prion protein accompanies a specific innate immune response.

PMID- 27880770
TI  - Comment on Re-Analysis of Data by Terluin, de Boer and de Vet.

PMID- 27880769
TI  - Effects of Treatment of Treadmill Combined with Electro-Acupuncture on Tibia Bone
      Mass and Substance PExpression of Rabbits with Sciatic Nerve Injury.
AB  - The peripheral nervous system may play an important role in normal bone
      maintenance and remodeling. Substance P (SP) is a neuropeptide associated with
      bone loss and formation that may mediate the effects of the nervous system. The
      purpose of this study is to determine if treadmill running combined with electro
      acupuncture at Jiaji acupoints (Jiaji-EA) affects tibial bone mass and SP
      expression in rabbits with sciatic nerve injury. Twenty-four juvenile male New
      Zealand white rabbits were randomly assigned to one of 4 groups: sham injury
      control (sham), sciatic never crush control (SNCr), treadmill running
      (treadmill), and Jiaji-EA combined with treadmill running (ET group). The SNCr,
      treadmill, and ET groups all had an induced sciatic never crush injury of
      approximately 2mm. Control groups received no intervention; the treadmill and ET
      groups were trained by treadmill; the ET group also received Jiaji-EA. After the
      4 weeks of treatment, toe-spreading index (TSI), BMD, bone strength, and SP
      expression in the tibia were significantly lower in the nerve injury groups
      (SNCr, treadmill, and ET) compared to the sham groups (p<0.05). Treatment
      (treadmill and ET groups) increased all measures compared to the SNCr group
      (p<0.05). Further, TSI, BMD, bone strength, and SP expression in the ET group
      were higher than the treadmill group (p<0.05). Our results indicate that
      treadmill therapy combined with electro-acupuncture at Jiaji acupoints prevents
      bone loss in rabbit tibias after sciatic nerve injury. This may occur in two
      ways: indirectly in association with axon regeneration and directly via loading
      on the bone mediated through increased SP expression. This study provides
      important evidence for the clinical treatment of bone loss after peripheral nerve
      injury.

PMID- 27880771
TI  - Differences in Connection Strength between Mental Symptoms Might Be Explained by
      Differences in Variance: Reanalysis of Network Data Did Not Confirm Staging.
AB  - BACKGROUND: The network approach to psychopathology conceives mental disorders as
      sets of symptoms causally impacting on each other. The strengths of the
      connections between symptoms are key elements in the description of those symptom
      networks. Typically, the connections are analysed as linear associations (i.e.,
      correlations or regression coefficients). However, there is insufficient
      awareness of the fact that differences in variance may account for differences in
      connection strength. Differences in variance frequently occur when subgroups are
      based on skewed data. An illustrative example is a study published in PLoS One
      (2013;8(3):e59559) that aimed to test the hypothesis that the development of
      psychopathology through "staging" was characterized by increasing connection
      strength between mental states. Three mental states (negative affect, positive
      affect, and paranoia) were studied in severity subgroups of a general population
      sample. The connection strength was found to increase with increasing severity in
      six of nine models. However, the method used (linear mixed modelling) is not
      suitable for skewed data. METHODS: We reanalysed the data using inverse Gaussian
      generalized linear mixed modelling, a method suited for positively skewed data
      (such as symptoms in the general population). RESULTS: The distribution of
      positive affect was normal, but the distributions of negative affect and paranoia
      were heavily skewed. The variance of the skewed variables increased with
      increasing severity. Reanalysis of the data did not confirm increasing connection
      strength, except for one of nine models. CONCLUSIONS: Reanalysis of the data did
      not provide convincing evidence in support of staging as characterized by
      increasing connection strength between mental states. Network researchers should
      be aware that differences in connection strength between symptoms may be caused
      by differences in variances, in which case they should not be interpreted as
      differences in impact of one symptom on another symptom.

PMID- 27880772
TI  - T Cell Production of IFNgamma in Response to TLR7/IL-12 Stimulates Optimal B Cell
      Responses to Viruses.
AB  - Knowledge of the processes that underlie IgG subclass switching could inform
      strategies designed to counteract infections and autoimmunity. Here we show that
      TLR7 ligands induce subsets of memory CD4 and CD8 T cells to secrete interferon
      gamma (IFNgamma) in the absence of antigen receptor stimulation. In turn, TLR
      ligation and IFNgamma cause B cells to express the transcription factor, T-bet,
      and to switch immunoglobulin production to IgG2a/c. Absence of TLR7 in T cells
      leads to the impaired T-bet expression in B cells and subsequent inefficient
      IgG2a isotype switching both in vitro and during the infection with Friend virus
      in vivo. Our results reveal a surprising mechanism of antiviral IgG subclass
      switching through T-cell intrinsic TLR7/IL-12 signaling.

PMID- 27880773
TI  - Do Bird Friendly(r) Coffee Criteria Benefit Mammals? Assessment of Mammal
      Diversity in Chiapas, Mexico.
AB  - Biodiversity-friendly coffee certifications offer a viable way to protect
      wildlife habitat while providing a financial incentive to farmers. Most studies
      related to these certifications focus on avian habitat requirements and it is not
      known whether these standards also apply to other wildlife, such as mammals, that
      inhabit the coffee landscapes. We assessed the non-volant mammalian fauna and
      their associated habitat requirements in 23 sites representing forest, Bird
      Friendly(r) shade, conventional shade, and sun coffee habitats. We used Sherman
      trap-grids to measure small mammal abundance and richness, while camera traps
      were set for medium-sized and large mammals. We detected 17 species of mammals,
      representing 11 families. This preliminary study indicates that coffee farms in
      this region provide an important refuge for mammalian wildlife. Mammal species
      density ranked significantly higher in Bird Friendly(r) coffee sites than other
      coffee habitats, although there was no significant difference for species
      richness (using Chao2 estimator) among the habitat types. No significant
      difference was found in small mammal abundance among the habitat types. We found
      a higher species density of medium and large mammals in sites with larger, more
      mature shade trees associated with, but not required by Bird Friendly(r)
      certification standards. However, lower strata vegetation (5 cm to 1 m tall), the
      only vegetation parameter found to increase abundance and density for small
      mammals, is not specified in the Bird Friendly(r) standards. Our findings suggest
      that although the standards devised for avian habitat do benefit mammals, further
      study is needed on the requirements specific for mammals that could be included
      to enhance the coffee habitat for mammals that inhabit these coffee landscapes.

PMID- 27880774
TI  - Transmissibility of the Influenza Virus during Influenza Outbreaks and Related
      Asymptomatic Infection in Mainland China, 2005-2013.
AB  - We collected 2768 Influenza-like illness emergency public health incidents from
      April 1, 2005 to November 30, 2013reported in the Emergency Public Reporting
      System. After screening by strict inclusion and exclusion criteria, there were
      613 outbreaks analyzed with susceptible-exposed-infectious/asymptomatic-removed
      model in order to estimate the proportion of asymptomatic individuals (p) and the
      effective reproduction number (Rt). The relation between Rt and viral subtypes,
      regions, outbreak sites, populations, and seasons were analyzed. The mean values
      of p of different subtypes ranged from 0.09 to 0.15, but could be as high as up
      to 0.94. Different subtypes, provinces, regions, and sites of outbreak had
      statistically significantly different Rt. In particular, the southern region also
      manifested different Rt by affected population size and seasonality. Our results
      provide China and also the rest of the world a reference to understand
      characteristics of transmission and develop prevention and control strategies.

PMID- 27880775
TI  - How Many Kinds of Birds Are There and Why Does It Matter?
AB  - Estimates of global species diversity have varied widely, primarily based on
      variation in the numbers derived from different inventory methods of arthropods
      and other small invertebrates. Within vertebrates, current diversity metrics for
      fishes, amphibians, and reptiles are known to be poor estimators, whereas those
      for birds and mammals are often assumed to be relatively well established. We
      show that avian evolutionary diversity is significantly underestimated due to a
      taxonomic tradition not found in most other taxonomic groups. Using a sample of
      200 species taken from a list of 9159 biological species determined primarily by
      morphological criteria, we applied a diagnostic, evolutionary species concept to
      a morphological and distributional data set that resulted in an estimate of
      18,043 species of birds worldwide, with a 95% confidence interval of 15,845 to
      20,470. In a second, independent analysis, we examined intraspecific genetic data
      from 437 traditional avian species, finding an average of 2.4 evolutionary units
      per species, which can be considered proxies for phylogenetic species. Comparing
      recent lists of species to that used in this study (based primarily on
      morphology) revealed that taxonomic changes in the past 25 years have led to an
      increase of only 9%, well below what our results predict. Therefore, our
      molecular and morphological results suggest that the current taxonomy of birds
      understimates avian species diversity by at least a factor of two. We suggest
      that a revised taxonomy that better captures avian species diversity will enhance
      the quantification and analysis of global patterns of diversity and distribution,
      as well as provide a more appropriate framework for understanding the
      evolutionary history of birds.

PMID- 27880777
TI  - Avian Influenza Risk Surveillance in North America with Online Media.
AB  - The use of Internet-based sources of information for health surveillance
      applications has increased in recent years, as a greater share of social and
      media activity happens through online channels. The potential surveillance value
      in online sources of information about emergent health events include early
      warning, situational awareness, risk perception and evaluation of health
      messaging among others. The challenge in harnessing these sources of data is the
      vast number of potential sources to monitor and developing the tools to translate
      dynamic unstructured content into actionable information. In this paper we
      investigated the use of one social media outlet, Twitter, for surveillance of
      avian influenza risk in North America. We collected AI-related messages over a
      five-month period and compared these to official surveillance records of AI
      outbreaks. A fully automated data extraction and analysis pipeline was developed
      to acquire, structure, and analyze social media messages in an online context.
      Two methods of outbreak detection; a static threshold and a cumulative-sum
      dynamic threshold; based on a time series model of normal activity were evaluated
      for their ability to discern important time periods of AI-related messaging and
      media activity. Our findings show that peaks in activity were related to real
      world events, with outbreaks in Nigeria, France and the USA receiving the most
      attention while those in China were less evident in the social media data. Topic
      models found themes related to specific AI events for the dynamic threshold
      method, while many for the static method were ambiguous. Further analyses of
      these data might focus on quantifying the bias in coverage and relation between
      outbreak characteristics and detectability in social media data. Finally, while
      the analyses here focused on broad themes and trends, there is likely additional
      value in developing methods for identifying low-frequency messages,
      operationalizing this methodology into a comprehensive system for visualizing
      patterns extracted from the Internet, and integrating these data with other
      sources of information such as wildlife, environment, and agricultural data.

PMID- 27880776
TI  - Early Left Parietal Activity Elicited by Direct Gaze: A High-Density EEG Study.
AB  - Gaze is one of the most important cues for human communication and social
      interaction. In particular, gaze contact is the most primary form of social
      contact and it is thought to capture attention. A very early-differentiated brain
      response to direct versus averted gaze has been hypothesized. Here, we used high
      density electroencephalography to test this hypothesis. Topographical analysis
      allowed us to uncover a very early topographic modulation (40-80 ms) of event
      related responses to faces with direct as compared to averted gaze. This
      modulation was obtained only in the condition where intact broadband faces-as
      opposed to high-pass or low-pas filtered faces-were presented. Source estimation
      indicated that this early modulation involved the posterior parietal region,
      encompassing the left precuneus and inferior parietal lobule. This supports the
      idea that it reflected an early orienting response to direct versus averted gaze.
      Accordingly, in a follow-up behavioural experiment, we found faster response
      times to the direct gaze than to the averted gaze broadband faces. In addition,
      classical evoked potential analysis showed that the N170 peak amplitude was
      larger for averted gaze than for direct gaze. Taken together, these results
      suggest that direct gaze may be detected at a very early processing stage,
      involving a parallel route to the ventral occipito-temporal route of face
      perceptual analysis.

PMID- 27880779
TI  - A Mighty Claw: Pinching Force of the Coconut Crab, the Largest Terrestrial
      Crustacean.
AB  - Crustaceans can exert a greater force using their claws than many animals can
      with other appendages. Furthermore, in decapods, the chela is a notable organ
      with multifunctional roles. The coconut crab, Birgus latro, is the largest
      terrestrial crustacean and has a remarkable ability to lift weights up to
      approximately 30 kg. However, the pinching force of this crab's chelae has not
      been previously investigated. In the present study, we measured the pinching
      force of the chelae in 29 wild coconut crabs (33-2,120 g in body weight). The
      maximum force ranged from 29.4 to 1,765.2 N, and showed a strong positive
      correlation with body mass. Based on the correlation between pinching force and
      body weight, the force potentially exerted by the largest crab (4 kg weight)
      reported in a previous study would be 3300 N, which greatly exceeds the pinching
      force of other crustaceans as well as the bite force of most terrestrial
      predators. The mighty claw is a terrestrial adaptation that is not only a weapon,
      which can be used to prevent predator attack and inhibit competitors, but is also
      a tool to hunt other terrestrial organisms with rigid exteriors, aiding in these
      organisms to be omnivores.

PMID- 27880778
TI  - Colonizing the High Arctic: Mitochondrial DNA Reveals Common Origin of Eurasian
      Archipelagic Reindeer (Rangifer tarandus).
AB  - In light of current debates on global climate change it has become important to
      know more on how large, roaming species have responded to environmental change in
      the past. Using the highly variable mitochondrial control region, we revisit
      theories of Rangifer colonization and propose that the High Arctic archipelagos
      of Svalbard, Franz Josef Land, and Novaia Zemlia were colonized by reindeer from
      the Eurasian mainland after the last glacial maximum. Comparing mtDNA control
      region sequences from the three Arctic archipelagos showed a strong genetic
      connection between the populations, supporting a common origin in the past. A
      genetic connection between the three archipelagos and two Russian mainland
      populations was also found, suggesting colonization of the Eurasian high Arctic
      archipelagos from the Eurasian mainland. The age of the Franz Josef Land material
      (>2000 years before present) implies that Arctic indigenous reindeer colonized
      the Eurasian Arctic archipelagos through natural dispersal, before humans
      approached this region.

PMID- 27880780
TI  - Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison.
AB  - Yellowstone National Park is home to one of the only plains bison populations
      that have continuously existed on their present landscape since prehistoric times
      without evidence of domestic cattle introgression. Previous studies characterized
      the relatively high levels of nuclear genetic diversity in these bison, but
      little is known about their mitochondrial haplotype diversity. This study
      assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and
      found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78
      (+/- 0.06). Spatial analysis of these mitochondrial DNA (mtDNA) haplotypes did
      not detect geographic population subdivision (FST = -0.06, p = 0.76). However, we
      identified two independent and historically important lineages in Yellowstone
      bison by combining data from 65 bison (defined by 120 polymorphic sites) from
      across North America representing a total of 30 different mitochondrial DNA
      haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages
      represent descendants of the 22 indigenous bison remaining in central Yellowstone
      in 1902. The other mitochondrial DNA lineage represents descendants of the 18
      females introduced from northern Montana in 1902 to supplement the indigenous
      bison population and develop a new breeding herd in the northern region of the
      park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone
      bison helps uncover a historical context of park restoration efforts during the
      early 1900s, provides evidence against a hypothesized mitochondrial disease in
      bison, and reveals the signature of recent hybridization between American plains
      bison (Bison bison bison) and Canadian wood bison (B. b. athabascae). Our study
      demonstrates how mitochondrial DNA can be applied to delineate the history of
      wildlife species and inform future conservation actions.

PMID- 27880782
TI  - Correction: Systemic Delivery of Recombinant Brain Derived Neurotrophic Factor
      (BDNF) in the R6/2 Mouse Model of Huntington's Disease.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0064037.].

PMID- 27880781
TI  - Assessment of Blood Pressure Control among Hypertensive Patients in Southwest
      Ethiopia.
AB  - BACKGROUND: The rate of blood pressure control among hypertensive patients is
      poor and the reasons for poor control of blood pressure remain poorly understood
      globally. OBJECTIVE: To assess the rate of blood pressure control among adult
      hypertensive patients at Jimma University Specialized Hospital. MATERIALS AND
      METHODS: We conducted a hospital based cross sectional study among adult
      hypertensive patients at Jimma University Specialized Hospital hypertension
      clinic from March 4, 2015 to April 3, 2015. Data on sociodemographic
      characteristics of the participants and adherence to antihypertensive
      medication(s) were collected from patients by face to face interview using a
      pretested structured questionnaire. Comorbidities, antihypertensive medication(s)
      and blood pressure measurements were collected retrospectively from medical
      records. Medication adherence was assessed using Morisky's Medication Adherence
      Scale-8 score. We did the statistical analysis using chi-square test and binary
      logistic regression with level of alpha set at 0.05. Statistical significance was
      considered for variables with p<0.05. RESULTS: Out of 311 participants, 286
      patients were eligible and were studied. More than half, 154 (53.8%), of the
      participants were males. The mean age of the participants was 54.8+/- 12.6 years
      (range 26 to 94). The majority, 196 (68.53%), of the participants were taking
      more than one antihypertensive medication. More than one third (39.5%) of the
      participants were non adherent to their medication(s). The rate of blood pressure
      control was 50.3%. In a univariate logistic regression analyses, age >=65 years
      old (P = 0.008), physical inactivity (p<0.001), chat chewing (P<0.001), adding
      salt to food (P<0.001), and coffee use (P<0.001) are significantly associated
      with uncontrolled blood pressure. CONCLUSION: Almost half of the hypertensive
      patients on follow up had uncontrolled blood pressure. We recommend better health
      education and care of patients to improve the rate of blood pressure control at
      the hospital.

PMID- 27880783
TI  - Comparability of Point-of-Care versus Central Laboratory Hemoglobin Determination
      in Emergency Patients at a Supra-Maximal Care Hospital.
AB  - Fulfilling the requirements of point-of-care testing (POCT) training regarding
      proper execution of measurements and compliance with internal and external
      quality control specifications is a great challenge. Our aim was to compare the
      values of the highly critical parameter hemoglobin (Hb) determined with POCT
      devices and central laboratory analyzer in the highly vulnerable setting of an
      emergency department in a supra maximal care hospital to assess the quality of
      POCT performance. In 2548 patients, Hb measurements using POCT devices (POCT-Hb)
      were compared with Hb measurements performed at the central laboratory (Hb-ZL).
      Additionally, sub collectives (WHO anemia classification, patients with Hb <8
      g/dl and suprageriatric patients (age >85y.) were analyzed. Overall, the
      correlation between POCT-Hb and Hb-ZL was highly significant (r = 0.96, p<0.001).
      Mean difference was -0.44g/dl. POCT-Hb values tended to be higher than Hb-ZL
      values (t(2547) = 36.1, p<0.001). Standard deviation of the differences was 0.62
      g/dl. Only in 26 patients (1%), absolute differences >2.5g/dl occurred. McNemar's
      test revealed significant differences regarding anemia diagnosis according to WHO
      definition for male, female and total patients (? p<0.001; ? p<0.001, total
      p<0.001). Hb-ZL resulted significantly more often in anemia diagnosis. In samples
      with Hb<8g/dl, McNemar's test yielded no significant difference (p = 0.169). In
      suprageriatric patients, McNemar's test revealed significant differences
      regarding anemia diagnosis according to WHO definition in male, female and total
      patients (? p<0.01; ? p = 0.002, total p<0.001). The difference between Hb-ZL and
      POCT-Hb with Hb<8g/dl was not statistically significant (<8g/dl, p = 1.000).
      Overall, we found a highly significant correlation between the analyzed
      hemoglobin concentration measurement methods, i.e. POCT devices and at the
      central laboratory. The results confirm the successful implementation of the
      presented POCT concept. Nevertheless some limitations could be identified in
      anemic patients stressing the importance of carefully examining clinically
      implausible results.

PMID- 27880784
TI  - CDH1 Missense Variant c.1679C>G (p.T560R) Completely Disrupts Normal Splicing
      through Creation of a Novel 5' Splice Site.
AB  - Disease-causing germline mutations in CDH1 cause Hereditary Diffuse Gastric
      Cancer (HDGC). For patients who meet the HDGC screening criteria, the
      identification and classification of the sequence variants found in CDH1 are
      critical for risk management of patients. In this report, we describe a germline
      CDH1 c.1679C>G (p.T560R) variant identified in a 50 year old man who was
      diagnosed with gastric cancer with a strong family history of gastric cancer (one
      living brother was diagnosed with gastric cancer at 63 and another brother died
      of gastric cancer at 45). cDNA analysis, involving fragment analysis and cloning,
      indicated that the p.T560R mutation created a novel 5' splice donor site, which
      led to a novel transcript with a 32 nucleotide deletion in exon 11. This abnormal
      transcript putatively produces a truncated CDH1 protein (E-cadherin) of 575 amino
      acids instead of 882. We also demonstrated that the variant completely abolishes
      normal splicing as the mutant allele does not generate any normal transcript.
      Furthermore, the CDH1 c.1679C>G (p.T560R) variant segregated with gastric cancer
      in all three family members affected with gastric cancer in this family. These
      results support the conclusion that CDH1 c.1679C>G (p.T560R) variant is a
      pathogenic mutation and contributes to HDGC through disruption of normal
      splicing.

PMID- 27880786
TI  - Effects of Pile Driving on the Residency and Movement of Tagged Reef Fish.
AB  - The potential effects of pile driving on fish populations and commercial
      fisheries have received significant attention given the prevalence of pile
      driving occurring in coastal habitats throughout the world. Behavioral impacts of
      sound generated from these activities on fish typically have a greater area of
      influence than physical injury, and may therefore adversely affect a greater
      portion of the local population. This study used acoustic telemetry to assess the
      movement, residency, and survival of 15 sheepshead (Archosargus probatocephalus)
      and 10 grey snapper (Lutjanus griseus) in Port Canaveral, Florida, USA, in
      response to 35 days of pile driving at a wharf complex. No obvious signs of
      mortality or injury to tagged fish were evident from the data. Received sound
      pressure levels from pile strikes on the interior of the wharf, where reef fish
      primarily occur, were on average 152-157 dB re 1 MUPa (peak). No significant
      decrease in sheepshead daytime residency was observed during pile driving within
      the central portion of the wharf and area of highest sound exposure, and no major
      indicators of displacement from the exposure wharf with the onset of pile driving
      were observed. There was evidence of potential displacement from the exposure
      wharf that coincided with the start of pile driving observed for 2 out of 4 grey
      snapper, along with a decrease in daytime residency for a subset of this species
      with high site fidelity prior to the event. Results indicate that snapper may be
      more likely to depart an area of pile driving disturbance more readily than
      sheepshead, but were less at risk for behavioral impact given the lower site
      fidelity of this species.

PMID- 27880785
TI  - Individual Differences in Dynamic Functional Brain Connectivity across the Human
      Lifespan.
AB  - Individual differences in brain functional networks may be related to complex
      personal identifiers, including health, age, and ability. Dynamic network theory
      has been used to identify properties of dynamic brain function from fMRI data,
      but the majority of analyses and findings remain at the level of the group. Here,
      we apply hypergraph analysis, a method from dynamic network theory, to quantify
      individual differences in brain functional dynamics. Using a summary metric
      derived from the hypergraph formalism-hypergraph cardinality-we investigate
      individual variations in two separate, complementary data sets. The first data
      set ("multi-task") consists of 77 individuals engaging in four consecutive
      cognitive tasks. We observe that hypergraph cardinality exhibits variation across
      individuals while remaining consistent within individuals between tasks;
      moreover, the analysis of one of the memory tasks revealed a marginally
      significant correspondence between hypergraph cardinality and age. This finding
      motivated a similar analysis of the second data set ("age-memory"), in which 95
      individuals, aged 18-75, performed a memory task with a similar structure to the
      multi-task memory task. With the increased age range in the age-memory data set,
      the correlation between hypergraph cardinality and age correspondence becomes
      significant. We discuss these results in the context of the well-known finding
      linking age with network structure, and suggest that hypergraph analysis should
      serve as a useful tool in furthering our understanding of the dynamic network
      structure of the brain.

PMID- 27880787
TI  - Seasonal and Spatial Environmental Influence on Opisthorchis viverrini
      Intermediate Hosts, Abundance, and Distribution: Insights on Transmission
      Dynamics and Sustainable Control.
AB  - BACKGROUND: Opisthorchis viverrini (Ov) is a complex-life-cycle trematode
      affecting 10 million people in SEA (Southeast Asia). Human infection occurs when
      infected cyprinid fish are consumed raw or undercooked. Ov requires three hosts
      and presents two free-living parasitic stages. As a consequence Ov transmission
      and infection in intermediate and human hosts are strongly mediated by
      environmental factors and understanding how environmental variability influences
      intermediate host abundance is critical. The objectives of this study were 1) to
      document water parameters, intermediate hosts abundance and infection spatio
      temporal variation, 2) to assess their causal relationships and identify windows
      of transmission risk. METHODOLOGY/PRINCIPAL FINDINGS: Fish and snails were
      collected monthly for one year at 12 sites in Lawa Lake, an Ov-endemic region of
      Khon Kaen Province in Northeast Thailand. Physicochemical water parameters [pH,
      temperature (Tp), dissolved oxygen (DO), Salinity, electrical conductivity (EC),
      total dissolved solid (TDS), nitrite nitrogen (NO2-N), lead (Pb), total coliform
      bacteria (TCB) and fecal coliform bacteria (FCB)] were measured. Multivariate
      analyses, linear models and kriging were used to characterize water parameter
      variation and its influence on host abundance and infection prevalence. We found
      that sampling sites could be grouped in three clusters and discriminated along a
      nitrogen-salinity gradient where higher levels in the lake's southern region
      predicted higher Bithynia relative abundance (P<0.05) and lower snail and fish
      species diversity (P<0.05). Highest Bithynia abundance occurred during rainy
      season (P<0.001), independently of site influence. Cyprinids were the most
      abundant fish family and higher cyprinid relative abundance was found in areas
      with higher Bithynia relative abundance (P<0.05). Ov infection in snails was
      anecdotal while Ov infection in fish was higher in the southern region (P<0.001)
      at sites showing high FCB. CONCLUSIONS/SIGNIFICANCE: Our results indicate that
      water contamination and waterways configuration can influence freshwater
      communities' assemblages possibly creating ideal conditions for sustained
      transmission. Sustainable control may require a better appreciation of the
      system's ecology with wise governance and development planning particularly in
      the current context of SEA agricultural intensification and landscape
      modification.

PMID- 27880788
TI  - Micro-CT vs. Whole Body Multirow Detector CT for Analysing Bone Regeneration in
      an Animal Model.
AB  - OBJECTIVES: Compared with multirow detector CT (MDCT), specimen (ex vivo) micro
      CT (MUCT) has a significantly higher (~ 30 x) spatial resolution and is
      considered the gold standard for assessing bone above the cellular level.
      However, it is expensive and time-consuming, and when applied in vivo, the
      radiation dose accumulates considerably. The aim of this study was to examine
      whether the lower resolution of the widely used MDCT is sufficient to
      qualitatively and quantitatively evaluate bone regeneration in rats. METHODS:
      Forty critical-size defects (5mm) were placed in the mandibular angle of rats and
      covered with coated bioactive titanium implants to promote bone healing. Five
      time points were selected (7, 14, 28, 56 and 112 days). MUCT and MDCT were used
      to evaluate the defect region to determine the bone volume (BV), tissue mineral
      density (TMD) and bone mineral content (BMC). RESULTS: MDCT constantly achieved
      higher BV values than MUCT (10.73+/-7.84 mm3 vs. 6.62+/-4.96 mm3, p<0.0001) and
      consistently lower TMD values (547.68+/-163.83 mm3 vs. 876.18+/-121.21 mm3,
      p<0.0001). No relevant difference was obtained for BMC (6.48+/-5.71 mm3 vs.
      6.15+/-5.21 mm3, p = 0.40). BV and BMC showed very strong correlations between
      both methods, whereas TMD was only moderately correlated (r = 0.87, r = 0.90, r =
      0.68, p < 0.0001). CONCLUSIONS: Due to partial volume effects, MDCT overestimated
      BV and underestimated TMD but accurately determined BMC, even in small volumes,
      compared with MUCT. Therefore, if bone quantity is a sufficient end point, a
      considerable number of animals and costs can be saved, and compared with in vivo
      MUCT, the required dose of radiation can be reduced.

PMID- 27880789
TI  - Targeting Ruminative Thinking in Adolescents at Risk for Depressive Relapse:
      Rumination-Focused Cognitive Behavior Therapy in a Pilot Randomized Controlled
      Trial with Resting State fMRI.
AB  - : This pilot randomized control trial was designed to examine whether Rumination
      Focused Cognitive Behavior Therapy (RFCBT) reduces rumination and residual
      depressive symptoms among adolescents with a history of Major Depressive Disorder
      (MDD) who are at risk for relapse. We also examined whether these changes in
      symptoms were associated with changes in functional connectivity of the posterior
      cingulate cortex (PCC), a key node in the default mode network (DMN). Thirty
      three adolescents (ages 12-18) were randomized to eight weeks of RFCBT or an
      assessment only (AO) control. Twenty two adolescents successfully completed fMRI
      scans pre- and post-intervention. Adolescents were recruited from the clinic and
      community and met criteria for at least one previous episode of MDD and were
      currently in full or partial remission. An Independent Evaluator interviewed
      parent and child before and after the eight-week intervention. The left PCC (-5, 
      50, 36) seed was used to probe resting state functional connectivity of the DMN.
      Adolescents who received RFCBT demonstrated reduced rumination (F = -2.76, df =
      112, p < .01, 95% CI [-4.72,-0.80]) and self-report depression across eight weeks
      (F = -2.58, df = 113, p < .01, 95% CI [-4.21, -0.94]). Youth who received RFCBT
      also demonstrated significant decreases in connectivity between the left PCC and
      the right inferior frontal gyrus (IFG) and bilateral inferior temporal gyri
      (ITG). Degree of change in connectivity was correlated with changes in self
      report depression and rumination. These data suggest that rumination can be
      reduced over eight weeks and that this reduction is associated with parallel
      decreases in residual depressive symptoms and decreased functional connectivity
      of the left PCC with cognitive control nodes. These changes may enhance the
      ability of vulnerable youth to stay well during the transition to adulthood.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01905267.

PMID- 27880790
TI  - Integrating Maternal and Children's Oral Health Promotion into Nursing and
      Midwifery Practice- A Systematic Review.
AB  - BACKGROUND: Globally, oral diseases contribute to major disease problems and oral
      health disparities persistently exist amongst vulnerable population groups. Two
      contributory factors to these challenges are the shortage of dental practitioners
      and the characteristic separation between the medical and dental professions.
      Nurses and midwives, in particular, are in a potentially excellent position to
      assist in basic oral health services such as dental health education and
      intraoral screening. We aimed to assess the effectiveness of integrating
      promotion of oral health of young children and their mothers into nursing and
      midwifery practice. METHODS AND FINDINGS: Seven electronic databases including
      CENTRAL, EMBASE, MEDLINE, GLOBAL HEALTH, CINHAL, Scopus, and Web of Science were
      systematically searched whereas conference proceedings and theses were retrieved
      via PROQUEST. Only randomized, non-randomized trials and observational studies on
      preventive oral health programs delivered by nurses or midwives in healthcare
      settings or through home visits were included. Two investigators reviewed full
      text articles independently to decide on eligibility for inclusion. Quality
      assessment was done using Cochrane tool for risk of bias for randomized trials
      and Downs and Black assessment tool for all other studies. Out of 3162 retrieved
      records, twenty one trials on oral health interventions incorporated into
      standard nursing practice were reviewed. Eighteen programs reported significant
      positive outcomes including reduction in caries experience, better oral hygiene
      and dietary habits and increased rates of dental visits amongst young children as
      reported by their caregivers. CONCLUSIONS: Incorporating oral health promotion
      into nursing practice is a promising initiative for reducing oral health
      disparities by contributing to a downward trend in caries experience and
      increased access to dental care especially amongst the poor disadvantaged
      communities.

PMID- 27880791
TI  - Common Noctule Bats Are Sexually Dimorphic in Migratory Behaviour and Body Size
      but Not Wing Shape.
AB  - Within the large order of bats, sexual size dimorphism measured by forearm length
      and body mass is often female-biased. Several studies have explained this through
      the effects on load carrying during pregnancy, intrasexual competition, as well
      as the fecundity and thermoregulation advantages of increased female body size.
      We hypothesized that wing shape should differ along with size and be under
      variable selection pressure in a species where there are large differences in
      flight behaviour. We tested whether load carrying, sex differential migration, or
      reproductive advantages of large females affect size and wing shape dimorphism in
      the common noctule (Nyctalus noctula), in which females are typically larger than
      males and only females migrate long distances each year. We tested for univariate
      and multivariate size and shape dimorphism using data sets derived from wing
      photos and biometric data collected during pre-migratory spring captures in
      Switzerland. Females had forearms that are on average 1% longer than males and
      are 1% heavier than males after emerging from hibernation, but we found no sex
      differences in other size, shape, or other functional characters in any wing
      parameters during this pre-migratory period. Female-biased size dimorphism
      without wing shape differences indicates that reproductive advantages of big
      mothers are most likely responsible for sexual dimorphism in this species, not
      load compensation or shape differences favouring aerodynamic efficiency during
      pregnancy or migration. Despite large behavioural and ecological sex differences,
      morphology associated with a specialized feeding niche may limit potential
      dimorphism in narrow-winged bats such as common noctules and the dramatic
      differences in migratory behaviour may then be accomplished through plasticity in
      wing kinematics.

PMID- 27880792
TI  - Telomere Length and Survival of Patients with Hepatocellular Carcinoma in the
      United States.
AB  - BACKGROUND: Telomere shortening is an important molecular event in hepatocellular
      carcinoma (HCC) initiation; however, its role in HCC progression and prognosis is
      less clear. Our study aimed to examine the association of telomere length with
      survival of patients with HCC. METHODS: We measured telomere length in tumor and
      adjacent non-tumor tissues from 126 persons with HCC in the United States (U.S.)
      who were followed for mortality outcomes. Relative telomere length (RTL) was
      measured by a monochrome multiplex quantitative polymerase chain reaction assay.
      Multivariable Cox proportional hazards modeling was used to calculate hazard
      ratios (HRs) and 95% CIs for the association between telomere length and all
      cause mortality. We also examined associations between telomere length and
      patient characteristics using multiple linear regression. RESULTS: During a mean
      follow-up of 6.0 years, 79 deaths occurred among 114 individuals for whom
      survival data were available. The ratio of RTL in tumor relative to non-tumor
      tissue was greater for individuals with regional or distant stage tumors (0.97)
      than localized stage tumors (0.77), and for individuals with grade III or IV
      tumors (0.95) than grade II (0.88) or grade I (0.67) tumors. An RTL ratio >=1 was
      not associated with survival (HR 0.92, 95% CI 0.55, 1.55) compared to a ratio <1,
      after adjusting for age at diagnosis, sex, tumor stage and tumor size. Similarly,
      RTL in the tumor and non-tumor tissue, respectively, were not associated with
      survival. CONCLUSIONS: This U.S. based study found that telomeres may be longer
      in more aggressive HCCs. There was no evidence, however, that telomere length was
      associated with survival of patients with HCC. Future investigations are
      warranted to clarify the role of telomere length in HCC prognosis.

PMID- 27880793
TI  - Seed Quality Traits Can Be Predicted with High Accuracy in Brassica napus Using
      Genomic Data.
AB  - Improving seed oil yield and quality are central targets in rapeseed (Brassica
      napus) breeding. The primary goal of our study was to examine and compare the
      potential and the limits of marker-assisted selection and genome-wide prediction
      of six important seed quality traits of B. napus. Our study is based on a bi
      parental population comprising 202 doubled haploid lines and a diverse validation
      set including 117 B. napus inbred lines derived from interspecific crosses
      between B. rapa and B. carinata. We used phenotypic data for seed oil, protein,
      erucic acid, linolenic acid, stearic acid, and glucosinolate content. All lines
      were genotyped with a 60k SNP array. We performed five-fold cross-validations in
      combination with linkage mapping and four genome-wide prediction approaches in
      the bi-parental population. Quantitative trait loci (QTL) with large effects were
      detected for erucic acid, stearic acid, and glucosinolate content, blazing the
      trail for marker-assisted selection. Despite substantial differences in the
      complexity of the genetic architecture of the six traits, genome-wide prediction
      models had only minor impacts on the prediction accuracies. We evaluated the
      effects of training population size, marker density and phenotyping intensity on
      the prediction accuracy. The prediction accuracy in the independent and
      genetically very distinct validation set still amounted to 0.14 for protein
      content and 0.17 for oil content reflecting the utility of the developed
      calibration models even in very diverse backgrounds.

PMID- 27880794
TI  - Phylogeography of Crimean Congo Hemorrhagic Fever Virus.
AB  - Crimean Congo hemorrhagic fever virus (CCHFV) is one of the most severe viral
      zoonozes. It is prevalent throughout Africa, Asia and southern Europe. Limited
      availability of sequence data has hindered phylogeographic studies. The complete
      genomic sequence of all three segments of 14 Crimean Congo hemorrhagic fever
      virus strains isolated from 1958-2000 in Russia, Central Asia and Africa was
      identified. Each genomic segment was independently subjected to continuous
      Bayesian phylogeographic analysis. The origin of each genomic segment was traced
      to Africa about 1,000-5,000 years ago. The virus was first introduced to South
      and Central Asia in the Middle Ages, and then spread to China, India and Russia.
      Reverse transfers of genomic segments from Asia to Africa were also observed. The
      European CCHFV genotype V was introduced to Europe via the Astrakhan region in
      South Russia 280-400 years ago and subsequently gradually spread westward in
      Russia, to Turkey and the Balkans less than 150 years ago. Only a few
      recombination events could be suggested in S and L genomic segments, while
      segment reassortment was very common. The median height of a non-reassortant
      phylogenetic tree node was 68-156 years. There were reassortment events within
      the European CCHFV lineage, but not with viruses from other locations. Therefore,
      CCHFV in Europe is a recently emerged zoonosis that represents a spillover from
      the global gene pool.

PMID- 27880796
TI  - Foxn1[Cre] Expression in the Male Germline.
AB  - Foxn1 (forkhead box N1), also known as the nude gene or winged-helix nude (Whn),
      is a forkhead transcription factor thought to be restricted to keratinocytes in
      the skin and thymus. Consistent with this tissue distribution, spontaneous or
      targeted mutation of Foxn1 results in the absence of both hair and a thymus.
      Genetic manipulation of the Foxn1 locus thus represents a powerful tool for
      tissue specific gene control in the skin and thymus, and tools such as Cre
      recombinase under control of the Foxn1 locus are widely used for this purpose.
      Unexpectedly, we show that Foxn1[Cre] exhibits unexpected activity in male germ
      cells, resulting in ubiquitous targeting of loxP-flanked alleles in all tissues
      in offspring from Foxn1[Cre] expressing male mice. Inheritance of recombined loxP
      alleles occurs independently of Cre inheritance (i.e., offspring lacking Cre
      nonetheless exhibit recombined alleles), suggesting that Foxn1[Cre] induced
      recombination in male germ cells must occur prior to meiosis in diploid germ
      cells. Together with previously published data, our results show that Foxn1, and
      alleles under its control, are expressed in the pre-meiotic male germline,
      revealing a new tool for germline targeting of genes, and raising important
      concerns for gender selection when using Foxn1 regulatory elements.

PMID- 27880795
TI  - The Association of Fatty Acid Levels and Gleason Grade among Men Undergoing
      Radical Prostatectomy.
AB  - BACKGROUND: Epidemiological data suggest that omega-6 (omega-6) fatty acids (FAs)
      may be associated with cancer incidence and/or cancer mortality, whereas omega-3
      FAs are potentially protective. We examined the association of the ratio of omega
      6 to omega-3 FA (omega-6:omega-3) and individual FA components with pathological
      results among men with prostate cancer (PCa) undergoing radical prostatectomy.
      METHODS: Sixty-nine men were included in the study. Components of omega-6
      (linoleic acid (LA), arachidonic acid (AA), and dihomo-gamma-linolenic acid
      (DGLA)) and omega-3 (docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA))
      were analyzed by liquid chromatography/mass selective detector separation.
      Logistic regression analysis was performed to determine association of FA with
      pathological high grade (Gleason >=4+3) disease. RESULTS: The were 35 men with
      low grade disease (Gleason <=3+4) and 34 men with high grade disease. Men with
      low grade disease were significantly younger (58y vs 61y, p = 0.012) and had
      lower D'Amico clinical classification (p = 0.001) compared to men with high grade
      disease. There was no significant association of omega-6:omega-3 with high grade
      disease (OR 0.93, p = 0.78), however overall omega-6, omega-3, and individual
      components of omega-6 and omega-3 FAs except EPA were significantly associated
      with high grade disease (omega-6: OR 3.37, 95% CI: 1.27,8.98; LA: OR 3.33, 95%
      CI:1.24,8.94; AA: OR 2.93, 95% CI:1.24,6.94; DGLA: OR 3.21, 95% CI:1.28,8.04;
      omega-3: OR 3.47, 95% CI:1.22,9.83; DHA: OR 3.13, 95% CI:1.26,7.74). omega-6 and
      omega-3 FA components were highly correlated (Spearman rho = 0.77). CONCLUSION:
      Higher levels of individual components of omega-6 and omega-3FAs may be
      associated with higher-grade PCa. IMPACT: Studies into the causative
      factors/pathways regarding FAs and prostate carcinogenesis may prove a potential
      association with PCa aggressiveness.

PMID- 27880797
TI  - Regulation and Maintenance of an Adoptive T-Cell Dependent Memory B Cell Pool.
AB  - We investigated the ability of monoclonal B cells to restore primary and
      secondary T-cell dependent antibody responses in adoptive immune-deficient hosts.
      Priming induced B cell activation and expansion, AID expression, antibody
      production and the generation of IgM+IgG- and IgM-IgG+ antigen-experienced B-cell
      subsets that persisted in the lymphopenic environment by cell division. Upon
      secondary transfer and recall the IgM-IgG+ cells responded by the production of
      antigen-specific IgG while the IgM+ memory cells secreted mainly IgM and little
      IgG, but generated new B cells expressing germinal center markers. The recall
      responses were more efficient if the antigenic boost was delayed suggesting that
      a period of adaptation is necessary before the transferred cells are able to
      respond. Overall these findings indicate that reconstitution of a functional and
      complete memory pool requires transfer of all different antigen-experienced B
      cell subsets. We also found that the size of the memory B cell pool did not rely
      on the number of the responding naive B cells, suggesting autonomous homeostatic
      controls for naive and memory B cells. By reconstituting a stable memory B cell
      pool in immune-deficient hosts using a monoclonal high-affinity B cell population
      we demonstrate the potential value of B cell adoptive immunotherapy.

PMID- 27880798
TI  - Added Value of 3D Proton-Density Weighted Images in Diagnosis of Intracranial
      Arterial Dissection.
AB  - BACKGROUND: An early and reliable diagnosis of intracranial arterial dissection
      is important to reduce the risk of neurological complication. The purpose of this
      study was to assess the clinical usefulness of three-dimensional high-resolution
      MRI (3D-HR-MRI) including pre- and post-contrast T1-weighted volumetric isotropic
      turbo spin echo acquisition with improved motion-sensitized driven equilibrium
      preparation (3D-iMSDE-T1) and proton-density weighted image (3D-PD) in detecting
      dissection and to evaluate the added value of 3D-PD in diagnosing intracranial
      arterial dissection. METHODS: We retrospectively recruited patients who underwent
      3D-HR-MRI with clinical suspicion of arterial dissection. Among them, we selected
      patients who were diagnosed with definite dissection according to the Spontaneous
      Cervicocephalic Arterial Dissections Study criteria. For each patient, the
      presence of intimal flap, intramural hematoma, and vessel dilatation were
      evaluated independently by two neuroradiologists on each sequence. Interobserver
      agreement was assessed. RESULTS: Seventeen patients (mean age: 41 +/- 10 [SD]
      years; 13 men) were diagnosed with definite dissection. The intimal flaps were
      more frequently detected on 3D-PD (88.2%, 15/17) than on 3D-iMSDE-T1 (29.4%,
      5/17), and post-contrast 3D-iMSDE-T1 (35.3%, 6/17; P = 0.006 and P = 0.004,
      respectively). No significant difference was found in the detection rate of
      intramural hematomas (59-71%) and vascular dilatations (47%) on each sequence.
      Interobserver agreement for detection of dissection findings showed almost
      perfect agreement (k = 0.84-1.00), except for detection of intimal flaps on pre
      contrast 3D-iMSDE-T1 (k = 0.62). After addition of 3D-PD to pre- and post
      contrast 3D-iMSDE-T1, more patients were diagnosed with definite dissection with
      the initial MRI (88.2% vs. 47.1%; P = 0.039). CONCLUSIONS: The intimal flap might
      be better visualized on the 3D-PD sequence than the 3D-iMSDE-T1 sequences,
      allowing diagnosis of definite dissection without follow-up imaging.

PMID- 27880799
TI  - Treatment of Oral Biofilms by a D-Enantiomeric Peptide.
AB  - Almost all dental diseases are caused by biofilms that consist of multispecies
      communities. DJK-5, which is a short D-enantiomeric, protease-resistant peptide
      with broad-spectrum anti-biofilm activity, was tested for its effect on oral
      multispecies biofilms. Peptide DJK-5 at 10 MUg/mL effectively prevented the
      growth of these microbes in culture media in a time-dependent manner. In addition
      to the prevention of growth, peptide DJK-5 completely killed both Streptococcus
      mutans and Enterococcus faecalis suspended from biofilms after 30 minutes of
      incubation in liquid culture media. DJK-5 also led to the effective killing of
      microbes in plaque biofilm. The proportion of bacterial cells killed by 10 MUg/mL
      of DJK-5 was similar after 1 and 3 days, both exceeding 85%. DJK-5 was able to
      significantly prevent biofilm formation over 3 days (P = 0.000). After 72 hours
      of exposure, DJK-5 significantly reduced and almost completely prevented plaque
      biofilm production by more than 90% of biovolume compared to untreated controls
      (P = 0.000). The proportion of dead biofilm bacteria at the 10 MUg/mL DJK-5
      concentration was similar for 1- and 3-day-old biofilms, whereby >86% of the
      bacteria were killed. DJK-5 was also able to kill >79% and >85% of bacteria,
      respectively, after one-time and three brief treatments of 3-day-old biofilms.
      The combination of DJK-5 and chlorhexidine showed the best bacterial killing
      among all treatments, with ~83% and >88% of bacterial cells killed after 1 and 3
      minutes, respectively. No significant difference was found in the percentage of
      biofilm killing amongst three donor plaque samples after DJK-5 treatment. In
      particular, DJK-5 showed strong performance in inhibiting biofilm development and
      eradicating pre-formed oral biofilms compared to L-enantiomeric peptide 1018. DJK
      5 was very effective against oral biofilms when used alone or combined with
      chlorhexidine, and may be a promising agent for use in oral anti-biofilm
      strategies in the future.

PMID- 27880800
TI  - Minimal In Vivo Efficacy of Iminosugars in a Lethal Ebola Virus Guinea Pig Model.
AB  - The antiviral properties of iminosugars have been reported previously in vitro
      and in small animal models against Ebola virus (EBOV); however, their effects
      have not been tested in larger animal models such as guinea pigs. We tested the
      iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)
      1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral
      efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850
      mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three
      times daily, caused no adverse effects and were well tolerated. A pilot study
      treating infected animals three times within an 8 hour period was promising with
      1 of 4 infected NB-DNJ treated animals surviving and the remaining three showing
      improved clinical signs. MON-DNJ showed no protective effects when EBOV-infected
      guinea pigs were treated. On histopathological examination, animals treated with
      NB-DNJ had reduced lesion severity in liver and spleen. However, a second study,
      in which NB-DNJ was administered at equally-spaced 8 hour intervals, could not
      confirm drug-associated benefits. Neither was any antiviral effect of iminosugars
      detected in an EBOV glycoprotein pseudotyped virus assay. Overall, this study
      provides evidence that NB-DNJ and MON-DNJ do not protect guinea pigs from a
      lethal EBOV-infection at the dose levels and regimens tested. However, the one
      surviving animal and signs of improvements in three animals of the NB-DNJ treated
      cohort could indicate that NB-DNJ at these levels may have a marginal beneficial
      effect. Future work could be focused on the development of more potent
      iminosugars.

PMID- 27880801
TI  - AMPA Receptor Antagonist NBQX Decreased Seizures by Normalization of Perineuronal
      Nets.
AB  - Epilepsy is a serious brain disorder with diverse seizure types and epileptic
      syndromes. AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzoquinoxaline-2,3-dione (NBQX) attenuates spontaneous recurrent seizures in
      rats. However, the anti-epileptic effect of NBQX in chronic epilepsy model is
      poorly understood. Perineuronal nets (PNNs), specialized extracellular matrix
      structures, surround parvalbumin-positive inhibitory interneurons, and play a
      critical role in neuronal cell development and synaptic plasticity. Here, we
      focused on the potential involvement of PNNs in the treatment of epilepsy by
      NBQX. Rats were intraperitoneally (i.p.) injected with pentylenetetrazole (PTZ,
      50 mg/kg) for 28 consecutive days to establish chronic epilepsy models.
      Subsequently, NBQX (20 mg/kg, i.p.) was injected for 3 days for the observation
      of behavioral measurements of epilepsy. The Wisteria floribundi agglutinin (WFA)
      labeled PNNs were measured by immunohistochemical staining to evaluate the PNNs.
      The levels of three components of PNNs such as tenascin-R, aggrecan and neurocan
      were assayed by Western blot assay. The results showed that there are reduction
      of PNNs and decrease of tenascin-R, aggrecan and neurocan in the medial
      prefrontal cortex (mPFC) in the rats injected with PTZ. However, NBQX treatment
      normalized PNNs, tenascin-R, aggrecan and neurocan levels. NBQX was sufficient to
      decrease seizures through increasing the latency to seizures, decrease the
      duration of seizure onset, and reduce the scores for the severity of seizures.
      Furthermore, the degradation of mPFC PNNs by chondroitinase ABC (ChABC)
      exacerbated seizures in PTZ-treated rats. Finally, the anti-epileptic effect of
      NBQX was reversed by pretreatment with ChABC into mPFC. These findings revealed
      that PNNs degradation in mPFC is involved in the pathophysiology of epilepsy and
      enhancement of PNNs may be effective for the treatment of epilepsy.

PMID- 27880802
TI  - Algebraic Topology of Multi-Brain Connectivity Networks Reveals Dissimilarity in
      Functional Patterns during Spoken Communications.
AB  - Human behaviour in various circumstances mirrors the corresponding brain
      connectivity patterns, which are suitably represented by functional brain
      networks. While the objective analysis of these networks by graph theory tools
      deepened our understanding of brain functions, the multi-brain structures and
      connections underlying human social behaviour remain largely unexplored. In this
      study, we analyse the aggregate graph that maps coordination of EEG signals
      previously recorded during spoken communications in two groups of six listeners
      and two speakers. Applying an innovative approach based on the algebraic topology
      of graphs, we analyse higher-order topological complexes consisting of mutually
      interwoven cliques of a high order to which the identified functional connections
      organise. Our results reveal that the topological quantifiers provide new
      suitable measures for differences in the brain activity patterns and inter-brain
      synchronisation between speakers and listeners. Moreover, the higher topological
      complexity correlates with the listener's concentration to the story, confirmed
      by self-rating, and closeness to the speaker's brain activity pattern, which is
      measured by network-to-network distance. The connectivity structures of the
      frontal and parietal lobe consistently constitute distinct clusters, which extend
      across the listener's group. Formally, the topology quantifiers of the multi
      brain communities exceed the sum of those of the participating individuals and
      also reflect the listener's rated attributes of the speaker and the narrated
      subject. In the broader context, the presented study exposes the relevance of
      higher topological structures (besides standard graph measures) for
      characterising functional brain networks under different stimuli.

PMID- 27880804
TI  - Dietary Intake and Eating Behaviours of Obese New Zealand Children and
      Adolescents Enrolled in a Community-Based Intervention Programme.
AB  - OBJECTIVES: The aim of this study was to describe dietary intake and eating
      behaviours of obese children and adolescents, and also to determine how these
      differ in Indigenous versus non-Indigenous children at enrolment in an obesity
      programme. METHODS: Baseline dietary intake and eating behaviour records were
      assessed from those enrolled in a clinical unblinded randomised controlled trial
      of a multi-disciplinary intervention. The setting was a community-based obesity
      programme in Taranaki, New Zealand. Children or adolescents who were enrolled
      from January 2012 to August 2014, with a BMI >=98th percentile or >91st centile
      with weight-related comorbidities were eligible. RESULTS: 239 participants (45%
      Maori, 45% NZ Europeans, 10% other ethnicities), aged 5-17 years were assessed.
      Two-thirds of participants experienced hyperphagia and half were not satiated
      after a meal. Comfort eating was reported by 62% of participants, and daily
      energy intake was above the recommended guidelines for 54%. Fruit and vegetable
      intake was suboptimal compared with the recommended 5 servings per day (mean 3.5
      [SD = 1.9] servings per day), and the mean weekly breakfasts were less than the
      national average (5.9 vs 6.5; p<0.0001). Median sweet drink intake amongst Maori
      was twice that of NZ Europeans (250 vs 125 ml per day; p = 0.0002). CONCLUSIONS:
      There was a concerning prevalence of abnormal eating behaviours and significant
      differences in dietary intake between obese participants and their national
      counterparts. Ethnic differences between Indigenous and non-Indigenous
      participants were also present, especially in relation to sweet drink
      consumption. Eating behaviours, especially sweet drink consumption and
      fruit/vegetable intake need to be addressed.

PMID- 27880805
TI  - Feasibility of Quantification of Intracranial Aneurysm Pulsation with 4D CTA with
      Manual and Computer-Aided Post-Processing.
AB  - BACKGROUND AND PURPOSE: The analysis of the pulsation of unruptured intracranial
      aneurysms might improve the assessment of their stability and risk of rupture.
      Pulsations can easily be concealed due to the small movements of the aneurysm
      wall, making post-processing highly demanding. We hypothesized that the
      quantification of aneurysm pulsation is technically feasible and can be improved
      by computer-aided post-processing. MATERIALS AND METHODS: Images of 14 cerebral
      aneurysms were acquired with an ECG-triggered 4D CTA. Aneurysms were post
      processed manually and computer-aided on a 3D model. Volume curves and random
      noise-curves were compared with the arterial pulse wave and volume curves were
      compared between both post-processing modalities. RESULTS: The aneurysm volume
      curves showed higher similarity with the pulse wave than the random curves
      (Hausdorff-distances 0.12 vs 0.25, p<0.01). Both post-processing methods did not
      differ in intra- (r = 0.45 vs r = 0.54, p>0.05) and inter-observer (r = 0.45 vs r
      = 0.54, p>0.05) reliability. Time needed for segmentation was significantly
      reduced in the computer-aided group (3.9 +/- 1.8 min vs 20.8 +/- 7.8 min,
      p<0.01). CONCLUSION: Our results show pulsatile changes in a subset of the
      studied aneurysms with the final prove of underlying volume changes remaining
      unsettled. Semi-automatic post-processing significantly reduces post-processing
      time but cannot yet replace manual segmentation.

PMID- 27880806
TI  - Choroidal Round Hyporeflectivities in Geographic Atrophy.
AB  - PURPOSE: In geographic atrophy (GA), choroidal vessels typically appear on
      structural optical coherence tomography (OCT) as hyperreflective round areas with
      highly reflective borders. We observed that some GA eyes show choroidal round
      hyporeflectivities with highly reflective borders beneath the atrophy, and futher
      investigated the charcteristcs by comparing structural OCT, indocyanine green
      angiography (ICGA) and OCT angiography (OCT-A). METHODS: Round hyporeflectivities
      were individuated from a pool of patients with GA secondary to non-neovascular
      age-related macular degeneration consecutively presenting between October 2015
      and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute
      San Raffaele. Patients underwent a complete ophthalmologic examination including
      ICGA, structural OCT and OCT-A. The correspondence between choroidal round
      hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were
      analyzed. RESULTS: Fifty eyes of 26 consecutive patients (17 females and 9 males;
      mean age 76.8+/-6.2 years) with GA were included. Twenty-nine round
      hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21
      patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities
      showed constantly a hyperreflective border and a backscattering on structural
      OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non
      detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA
      area was greater in eyes with compared to eyes without round hyporeflectivities
      (9.30+/-5.74 and 5.57+/-4.48mm2, respectively; p = 0.01). CONCLUSIONS: Our
      results suggest that most round hyporeflectivities beneath GA may represent non
      perfused or hypo-perfused choroidal vessels with non-detectable flow.

PMID- 27880803
TI  - Wdr68 Mediates Dorsal and Ventral Patterning Events for Craniofacial Development.
AB  - Birth defects are among the leading causes of infant mortality and contribute
      substantially to illness and long-term disability. Defects in Bone Morphogenetic
      Protein (BMP) signaling are associated with cleft lip/palate. Many craniofacial
      syndromes are caused by defects in signaling pathways that pattern the cranial
      neural crest cells (CNCCs) along the dorsal-ventral axis. For example,
      auriculocondylar syndrome is caused by impaired Endothelin-1 (Edn1) signaling,
      and Alagille syndrome is caused by defects in Jagged-Notch signaling. The BMP,
      Edn1, and Jag1b pathways intersect because BMP signaling is required for ventral
      edn1 expression that, in turn, restricts jag1b to dorsal CNCC territory. In
      zebrafish, the scaffolding protein Wdr68 is required for edn1 expression and
      subsequent formation of the ventral Meckel's cartilage as well as the dorsal
      Palatoquadrate. Here we report that wdr68 activity is required between the 17
      somites and prim-5 stages, that edn1 functions downstream of wdr68, and that
      wdr68 activity restricts jag1b, hey1, and grem2 expression from ventral CNCC
      territory. Expression of dlx1a and dlx2a was also severely reduced in anterior
      dorsal and ventral 1st arch CNCC territory in wdr68 mutants. We also found that
      the BMP agonist isoliquiritigenin (ISL) can partially rescue lower jaw formation
      and edn1 expression in wdr68 mutants. However, we found no significant defects in
      BMP reporter induction or pSmad1/5 accumulation in wdr68 mutant cells or
      zebrafish. The Transforming Growth Factor Beta (TGF-beta) signaling pathway is
      also known to be important for craniofacial development and can interfere with
      BMP signaling. Here we further report that TGF-beta interference with BMP
      signaling was greater in wdr68 mutant cells relative to control cells. To
      determine whether interference might also act in vivo, we treated wdr68 mutant
      zebrafish embryos with the TGF-beta signaling inhibitor SB431542 and found
      partial rescue of edn1 expression and craniofacial development. While ISL
      treatment failed, SB431542 partially rescued dlx2a expression in wdr68 mutants.
      Together these findings reveal an indirect role for Wdr68 in the BMP-Edn1-Jag1b
      signaling hierarchy and dorso-anterior expression of dlx1a/2a.

PMID- 27880807
TI  - Human Genome-Wide RNAi Screen for Host Factors That Facilitate Salmonella
      Invasion Reveals a Role for Potassium Secretion in Promoting Internalization.
AB  - Salmonella enterica can actively invade the gastro-intestinal epithelium. This
      frequently leads to diarrheal disease, and also gives the pathogen access to
      phagocytes that can serve as vehicles for dissemination into deeper tissue. The
      ability to invade host cells is also important in maintaining the carrier state.
      While much is known about the bacterial factors that promote invasion, relatively
      little is known about the host factors involved. To gain insight into how
      Salmonella enterica serovar Typhimurium is able to invade normally non-phagocytic
      cells, we undertook a global RNAi screen with S. Typhimurium-infected human
      epithelial cells. In all, we identified 633 genes as contributing to bacterial
      internalization. These genes fall into a diverse group of functional categories
      revealing that cytoskeletal regulators are not the only factors that modulate
      invasion. In fact, potassium ion transport was the most enriched molecular
      function category in our screen, reinforcing a link between potassium and
      internalization. In addition to providing new insights into the molecular
      mechanisms underlying the ability of pathogens to invade host cells, all 633 host
      factors identified are candidates for new anti-microbial targets for treating
      Salmonella infections, and may be useful in curtailing infections with other
      pathogens as well.

PMID- 27880808
TI  - Natural Schistosoma mansoni Infection in the Wild Reservoir Nectomys squamipes
      Leads to Excessive Lipid Droplet Accumulation in Hepatocytes in the Absence of
      Liver Functional Impairment.
AB  - Schistosomiasis is a neglected tropical disease of a significant public health
      impact. The water rat Nectomys squamipes is one of the most important non-human
      hosts in the schistosomiasis mansoni transmission in Brazil, being considered a
      wild reservoir. Cellular mechanisms that contribute to the physiological
      adaptation of this rodent to the Schistosoma mansoni parasite are poorly
      understood. Here we identified, for the first time, that a hepatic steatosis, a
      condition characterized by excessive lipid accumulation with formation of lipid
      droplets (LDs) within hepatocytes, occurs in response to the natural S. mansoni
      infection of N. squamipes, captured in an endemic region. Significant increases
      of LD area in the hepatic tissue and LD numbers/hepatocyte, detected by
      quantitative histopathological and ultrastructural analyses, were paralleled by
      increased serum profile (total cholesterol and triglycerides) in infected
      compared to uninfected animals. Raman spectroscopy showed high content of
      polyunsaturated fatty acids (PUFAs) in the liver of both groups. MALDI-TOFF mass
      spectroscopy revealed an amplified pool of omega-6 PUFA arachidonic acid in the
      liver of infected animals. Assessment of liver functional activity by the levels
      of hepatic transaminases (ALT and AST) did not detect any alteration during the
      natural infection. In summary, this work demonstrates that the natural infection
      of the wild reservoir N. squamipes with S. mansoni elicits hepatic steatosis in
      the absence of liver functional harm and that accumulation of lipids, markedly
      PUFAs, coexists with low occurrence of inflammatory granulomatous processes,
      suggesting that lipid stores may be acting as a protective mechanism for dealing
      with the infection.

PMID- 27880810
TI  - A Global Model for Bankruptcy Prediction.
AB  - The recent world financial crisis has increased the number of bankruptcies in
      numerous countries and has resulted in a new area of research which responds to
      the need to predict this phenomenon, not only at the level of individual
      countries, but also at a global level, offering explanations of the common
      characteristics shared by the affected companies. Nevertheless, few studies focus
      on the prediction of bankruptcies globally. In order to compensate for this lack
      of empirical literature, this study has used a methodological framework of
      logistic regression to construct predictive bankruptcy models for Asia, Europe
      and America, and other global models for the whole world. The objective is to
      construct a global model with a high capacity for predicting bankruptcy in any
      region of the world. The results obtained have allowed us to confirm the
      superiority of the global model in comparison to regional models over periods of
      up to three years prior to bankruptcy.

PMID- 27880809
TI  - Molecular Analysis of Glucose-6-Phosphate Dehydrogenase Gene Mutations in
      Bangladeshi Individuals.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked human
      enzyme defect of red blood cells (RBCs). Individuals with this gene defect appear
      normal until exposed to oxidative stress which induces hemolysis. Consumption of
      certain foods such as fava beans, legumes; infection with bacteria or virus; and
      use of certain drugs such as primaquine, sulfa drugs etc. may result in lysis of
      RBCs in G6PD deficient individuals. The genetic defect that causes G6PD
      deficiency has been identified mostly as single base missense mutations. One
      hundred and sixty G6PD gene mutations, which lead to amino acid substitutions,
      have been described worldwide. The purpose of this study was to detect G6PD gene
      mutations in hospital-based settings in the local population of Dhaka city,
      Bangladesh. Qualitative fluorescent spot test and quantitative enzyme activity
      measurement using RANDOX G6PDH kit were performed for analysis of blood specimens
      and detection of G6PD-deficient participants. For G6PD-deficient samples, PCR was
      done with six sets of primers specific for G6PD gene. Automated Sanger sequencing
      of the PCR products was performed to identify the mutations in the gene. Based on
      fluorescence spot test and quantitative enzyme assay followed by G6PD gene
      sequencing, 12 specimens (11 males and one female) among 121 clinically suspected
      patient-specimens were found to be deficient, suggesting a frequency of 9.9% G6PD
      deficiency. Sequencing of the G6PD-deficient samples revealed c.C131G
      substitution (exon-3: Ala44Gly) in six samples, c.G487A substitution (exon
      6:Gly163Ser) in five samples and c.G949A substitution (exon-9: Glu317Lys) of
      coding sequence in one sample. These mutations either affect NADP binding or
      disrupt protein structure. From the study it appears that Ala44Gly and Gly163Ser
      are the most common G6PD mutations in Dhaka, Bangladesh. This is the first study
      of G6PD mutations in Bangladesh.

PMID- 27880812
TI  - Quantifying Risk for Anxiety Disorders in Preschool Children: A Machine Learning
      Approach.
AB  - Early childhood anxiety disorders are common, impairing, and predictive of
      anxiety and mood disorders later in childhood. Epidemiological studies over the
      last decade find that the prevalence of impairing anxiety disorders in preschool
      children ranges from 0.3% to 6.5%. Yet, less than 15% of young children with an
      impairing anxiety disorder receive a mental health evaluation or treatment. One
      possible reason for the low rate of care for anxious preschoolers is the lack of
      affordable, timely, reliable and valid tools for identifying young children with
      clinically significant anxiety. Diagnostic interviews assessing psychopathology
      in young children require intensive training, take hours to administer and code,
      and are not available for use outside of research settings. The Preschool Age
      Psychiatric Assessment (PAPA) is a reliable and valid structured diagnostic
      parent-report interview for assessing psychopathology, including anxiety
      disorders, in 2 to 5 year old children. In this paper, we apply machine-learning
      tools to already collected PAPA data from two large community studies to identify
      sub-sets of PAPA items that could be developed into an efficient, reliable, and
      valid screening tool to assess a young child's risk for an anxiety disorder.
      Using machine learning, we were able to decrease by an order of magnitude the
      number of items needed to identify a child who is at risk for an anxiety disorder
      with an accuracy of over 96% for both generalized anxiety disorder (GAD) and
      separation anxiety disorder (SAD). Additionally, rather than considering GAD or
      SAD as discrete/binary entities, we present a continuous risk score representing
      the child's risk of meeting criteria for GAD or SAD. Identification of a short
      question-set that assesses risk for an anxiety disorder could be a first step
      toward development and validation of a relatively short screening tool feasible
      for use in pediatric clinics and daycare/preschool settings.

PMID- 27880813
TI  - Transcranial Doppler-Based Surrogates for Cerebral Blood Flow: A Statistical
      Study.
AB  - It is commonly assumed that perfusion in a given cerebral territory can be
      inferred from Blood Flow Velocity (BFV) measurements in the corresponding stem
      artery. In order to test this hypothesis, we construct a cerebral blood flow
      (CBF) estimator based on transcranial Doppler (TCD) blood flow velocity and ten
      other easily available patient characteristics and clinical parameters. A total
      of 261 measurements were collected from 88 older patients. The estimator is based
      on local regression (Random Forest). Its performance is analyzed against baseline
      CBF from 3-D pseudocontinuous arterial spin labeling (pCASL) magnetic resonance
      imaging (MRI). Patient specific CBF predictions are of poor quality (r = 0.41 and
      p-value = 4.5 * 10-12); the hypothesis is thus not clearly supported by evidence.

PMID- 27880814
TI  - Health Care Professionals' Understandings of Cross-Cultural Interaction in End-of
      Life Care: A Focus Group Study.
AB  - OBJECTIVE: The academic debate on cross-cultural interaction within the context
      of end-of-life care takes for granted that this interaction is challenging.
      However, few empirical studies have actually focused on what health care
      professionals think about this interaction. This study aimed to explore health
      care professionals' understandings of cross-cultural interaction during end-of
      life care. METHODS: Sixty end-of-life care professionals were recruited from
      eleven care units in Sweden to take part in focus group interviews. These
      interviews were analyzed using qualitative content analysis. RESULTS: The health
      care professionals interviewed talked about cross-cultural interaction in end-of
      life care as interaction that brings about uncertainty, stress and frustration
      even though they had limited experience of this type of interaction. The focus
      group discussions brought attention to four specific challenges that they
      expected to meet when they care for patients with migrant backgrounds since they
      took for granted that they would have an ethno-cultural background that is
      different to their own. These challenges had to do with communication barriers,
      'unusual' emotional and pain expressions, the expectation that these patients'
      families would be 'different' and the anticipation that these patients and their
      families lack knowledge. At the core of the challenges in question is the idea
      that cross-cultural interaction means meeting "the unknown". In addition, the end
      of-life care professionals interviewed talked about patients whose backgrounds
      they did not share in homogenizing terms. It is against this backdrop that they
      worried about their ability to provide end-of-life care that is individualized
      enough to meet the needs of these patients. CONCLUSIONS: The study suggests that
      end-of-life care professionals who regard cross-cultural interaction in this
      manner could face actual challenges when caring for patients whose backgrounds
      they regard as "the unknown" since they anticipate a variety of challenges and do
      not seem confident enough that they can provide good quality care when cross
      cultural interaction is at stake.

PMID- 27880811
TI  - Oral Ondansetron versus Domperidone for Acute Gastroenteritis in Pediatric
      Emergency Departments: Multicenter Double Blind Randomized Controlled Trial.
AB  - The use of antiemetics for vomiting in acute gastroenteritis in children is still
      a matter of debate. We conducted a double-blind randomized trial to evaluate
      whether a single oral dose of ondansetron vs domperidone or placebo improves
      outcomes in children with gastroenteritis. After failure of initial oral
      rehydration administration, children aged 1-6 years admitted for gastroenteritis
      to the pediatric emergency departments of 15 hospitals in Italy were randomized
      to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg)
      or placebo. The primary outcome was the percentage of children receiving
      nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate
      statistical significance (and 98.6% CI were calculated) as a result of having
      carried out two interim analyses. 1,313 children were eligible for the first
      attempt with oral rehydration solution, which was successful for 832 (63.4%); 356
      underwent randomization (the parents of 125 children did not give consent): 118
      to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed
      intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in
      the domperidone and placebo groups, respectively. Ondansetron reduced the risk of
      intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20
      0.83) and domperidone (RR 0.47, 98.6% CI 0.23-0.97). No differences for adverse
      events were seen among groups. In a context of emergency care, 6 out of 10
      children aged 1-6 years with vomiting due to gastroenteritis and without severe
      dehydration can be managed effectively with administration of oral rehydration
      solution alone. In children who fail oral rehydration, a single oral dose of
      ondansetron reduces the need for intravenous rehydration and the percentage of
      children who continue to vomit, thereby facilitating the success of oral
      rehydration. Domperidone was not effective for the symptomatic treatment of
      vomiting during acute gastroenteritis.

PMID- 27880815
TI  - Validation of a Bayesian Adaptive Estimation Technique in the Stop-Signal Task.
AB  - The Stop Signal Task (SST), a commonly used measure of response inhibition, uses
      standard psychophysical methods to gain an estimate of the time needed to
      withhold a prepotent response. Under some circumstances, conventional forms of
      the SST are impractical to use because of the large number of trials necessary to
      gain a reliable estimate of the speed of inhibition. Here we applied to the SST
      an adaptive method for estimating psychometric parameters that can find reliable
      threshold estimates over a relatively small number of trials. The Psi adaptive
      staircase, which uses a Bayesian algorithm to find the most likely parameters of
      a psychophysical function, was used to estimate the critical stop signal delay at
      which the probability of successful response inhibition equals 0.5. Using
      computational modeling and adult participants, estimates of stop signal reaction
      time (SSRT) based on the Psi staircase were compared to estimates using the
      method of constant stimuli and a standard staircase method of adjustment. Results
      demonstrate that a reliable estimate of SSRT can be gained very quickly (20-30
      stop trials), making the method very useful for testing populations that cannot
      maintain concentration for long periods or for rapidly obtaining multiple SSRT
      estimates from healthy adult participants.

PMID- 27880816
TI  - Paradoxical Sleep Deprivation Causes Cardiac Dysfunction and the Impairment Is
      Attenuated by Resistance Training.
AB  - BACKGROUND: Paradoxical sleep deprivation activates the sympathetic nervous
      system and the hypothalamus-pituitary-adrenal axis, subsequently interfering with
      the cardiovascular system. The beneficial effects of resistance training are
      related to hemodynamic, metabolic and hormonal homeostasis. We hypothesized that
      resistance training can prevent the cardiac remodeling and dysfunction caused by
      paradoxical sleep deprivation. METHODS: Male Wistar rats were distributed into
      four groups: control (C), resistance training (RT), paradoxical sleep deprivation
      for 96 hours (PSD96) and both resistance training and sleep deprivation
      (RT/PSD96). Doppler echocardiograms, hemodynamics measurements, cardiac
      histomorphometry, hormonal profile and molecular analysis were evaluated.
      RESULTS: Compared to the C group, PSD96 group had a higher left ventricular
      systolic pressure, heart rate and left atrium index. In contrast, the left
      ventricle systolic area and the left ventricle cavity diameter were reduced in
      the PSD96 group. Hypertrophy and fibrosis were also observed. Along with these
      alterations, reduced levels of serum testosterone and insulin-like growth factor
      1 (IGF-1), as well as increased corticosterone and angiotensin II, were observed
      in the PSD96 group. Prophylactic resistance training attenuated most of these
      changes, except angiotensin II, fibrosis, heart rate and concentric remodeling of
      left ventricle, confirmed by the increased of NFATc3 and GATA-4, proteins
      involved in the pathologic cardiac hypertrophy pathway. CONCLUSIONS: Resistance
      training effectively attenuates cardiac dysfunction and hormonal imbalance
      induced by paradoxical sleep deprivation.

PMID- 27880817
TI  - Melissa officinalis Protects against Doxorubicin-Induced Cardiotoxicity in Rats
      and Potentiates Its Anticancer Activity on MCF-7 Cells.
AB  - Cardiotoxicity is a limiting factor of doxorubicin (DOX)-based anticancer
      therapy. Due to its beneficial effects, we investigated whether standardized
      extract of Melissa officinalis (MO) can attenuate doxorubicin-induced
      cardiotoxicity and can potentiate the efficacy of DOX against human breast cancer
      cells. MO was administered orally to male albino rats once daily for 10
      consecutive days at doses of 250, 500 and 750 mg/kg b.wt. DOX (15 mg/kg b.wt.
      i.p.) was administered on the 8th day. MO protected against DOX-induced leakage
      of cardiac enzymes and histopathological changes. MO ameliorated DOX-induced
      oxidative stress as evidenced by decreasing lipid peroxidation, protein oxidation
      and total oxidant capacity depletion and by increasing antioxidant capacity.
      Additionally, MO pretreatment inhibited inflammatory responses to DOX by
      decreasing the expressions of nuclear factor kappa-B, tumor necrosis factor-alpha
      and cyclooxygenase-2 and the activity of myeloperoxidase. MO ameliorated DOX
      induced apoptotic tissue damage in heart of rats. In vitro study showed that MO
      augmented the anticancer efficacy of DOX in human breast cancer cells (MCF-7) and
      potentiated oxidative damage and apoptosis. Thus, combination of DOX and MO may
      prove future cancer treatment protocols safer and more efficient.

PMID- 27880818
TI  - Merkel Cell Polyomavirus Small T Antigen Promotes Pro-Glycolytic Metabolic
      Perturbations Required for Transformation.
AB  - Merkel cell polyomavirus (MCPyV) is an etiological agent of Merkel cell carcinoma
      (MCC), a highly aggressive skin cancer. The MCPyV small tumor antigen (ST) is
      required for maintenance of MCC and can transform normal cells. To gain insight
      into cellular perturbations induced by MCPyV ST, we performed transcriptome
      analysis of normal human fibroblasts with inducible expression of ST. MCPyV ST
      dynamically alters the cellular transcriptome with increased levels of glycolytic
      genes, including the monocarboxylate lactate transporter SLC16A1 (MCT1).
      Extracellular flux analysis revealed increased lactate export reflecting elevated
      aerobic glycolysis in ST expressing cells. Inhibition of MCT1 activity suppressed
      the growth of MCC cell lines and impaired MCPyV-dependent transformation of IMR90
      cells. Both NF-kappaB and MYC have been shown to regulate MCT1 expression. While
      MYC was required for MCT1 induction, MCPyV-induced MCT1 levels decreased
      following knockdown of the NF-kappaB subunit RelA, supporting a synergistic
      activity between MCPyV and MYC in regulating MCT1 levels. Several MCC lines had
      high levels of MYCL and MYCN but not MYC. Increased levels of MYCL was more
      effective than MYC or MYCN in increasing extracellular acidification in MCC
      cells. Our results demonstrate the effects of MCPyV ST on the cellular
      transcriptome and reveal that transformation is dependent, at least in part, on
      elevated aerobic glycolysis.

PMID- 27880819
TI  - Risk Assessment of Patients Undergoing Transfemoral Aortic Valve Implantation
      upon Admission for Post-Interventional Intensive Care and Surveillance:
      Implications on Short- and Midterm Outcomes.
AB  - BACKGROUND: Several studies have found that standard risk scores inaccurately
      reflect risk in TAVI cohorts. The assessment of mortality risk upon post
      interventional ICU admission is important to optimizing clinical management. This
      study sought to determine outcomes and factors affecting mortality in patients
      admitted to the intensive care unit (ICU) after transcatheter aortic valve
      implantation (TAVI), and to analyze and compare the predictive values of SAPS II
      and EuroSCORE. METHODS AND FINDINGS: 214 consecutive patients treated with
      transfemoral TAVI (2006-2012) admitted to the ICU in an academic tertiary-care
      university hospital, were included in this retrospective data analysis. The
      overall 30-day mortality rate was 7%. Non-survivors at 30-days and survivors
      showed differences in the rates of catecholamine therapy upon ICU admission (93
      vs. 29%; p<0.001), stroke (20 vs. 1%;p<0.001), sepsis (27 vs. 2%;p<0.001), kidney
      injury (83 vs. 56%; log-rank p<0.001), catecholamine therapy (88 vs. 61%;log-rank
      p<0.001) and vascular complications (60 vs. 17%; p<0.001). Mean SAPS II score and
      predicted mortality were higher in non-survivors (38.1+/-7.0 vs. 29.9+/
      6.2;p<0.001 and 23.1+/-11.7 vs. 10.5+/-8.2;p<0.001, retrospectively), whereas the
      logistic EuroSCORE could not discriminate between the groups (p = 0.555). Among
      the biochemical parameters, the maximum values of creatinine, procalcitonin, and
      troponin I during the first 48 h after ICU admission were significantly higher in
      non-survivors. Multivariate analysis of baseline characteristics and
      complications associated with two-year mortality showed no significant results.
      CONCLUSIONS: The SAPS II is a good tool for estimating ICU mortality immediately
      after performing the TAVI procedure and provides valuable information for other
      known predictors of mortality.

PMID- 27880820
TI  - From Lab to Lake - Evaluation of Current Molecular Methods for the Detection of
      Infectious Enteric Viruses in Complex Water Matrices in an Urban Area.
AB  - Quantitative PCR methods are commonly used to monitor enteric viruses in the
      aquatic environment because of their high sensitivity, short reaction times and
      relatively low operational cost. However, conclusions for public health drawn
      from results of such molecular techniques are limited due to their inability to
      determine viral infectivity. Ethidium monoazide (EMA) and propidium monoazide
      (PMA) are capable to penetrate the damaged or compromised capsid of the
      inactivated viruses and bind to the viral nucleic acids. We assessed whether dye
      treatment is a suitable approach to improve the ability of qPCR to distinguish
      between infectious and non-infectious human adenovirus, enterovirus and rotavirus
      A in surface water of an urban river and sewage before and after UV disinfection.
      Like the gold standard of cell culture assays, pretreatment EMA-/PMA-qPCR
      succeeded in removing false positive results which would lead to an
      overestimation of the viral load if only qPCR of the environmental samples was
      considered. A dye pretreatment could therefore provide a rapid and relatively
      inexpensive tool to improve the efficacy of molecular quantification methods in
      regards to viral infectivity.

PMID- 27880821
TI  - Inhibition of the TGFbeta Pathway Enhances Retinal Regeneration in Adult
      Zebrafish.
AB  - In contrast to the mammalian retina, the zebrafish retina exhibits the potential
      for lifelong retinal neurogenesis and regeneration even after severe damage.
      Previous studies have shown that the transforming growth factor beta (TGFbeta)
      signaling pathway is activated during the regeneration of different tissues in
      the zebrafish and is needed for regeneration in the heart and the fin. In this
      study, we have investigated the role of the TGFbeta pathway in the N-methyl-N
      nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and
      regeneration in adult zebrafish. Immunohistochemical staining for phosphorylated
      Smad3 was elevated during retinal regeneration, and phosphorylated Smad3 co
      localized with proliferating cell nuclear antigen and glutamine synthetase,
      indicating TGFbeta pathway activation in proliferating Muller glia. Inhibiting
      the TGFbeta signaling pathway using a small molecule inhibitor (SB431542)
      resulted in accelerated recovery from retinal degeneration. Accordingly, we
      observed increased cell proliferation in the outer nuclear layer at days 3 to 8
      after MNU treatment. In contrast to the observations in the heart and the fin,
      the inhibition of the TGFbeta signaling pathway resulted in increased
      proliferation after the induction of retinal degeneration. A better understanding
      of the underlying pathways with the possibility to boost retinal regeneration in
      adult zebrafish may potentially help to stimulate such proliferation also in
      other species.

PMID- 27880823
TI  - Will Gay Sex-Seeking Mobile Phone Applications Facilitate Group Sex? A Cross
      Sectional Online Survey among Men Who Have Sex with Men in China.
AB  - INTRODUCTION: China is amidst a sexual revolution, with changing sexual practices
      and behaviors. Sex-seeking mobile phone applications (gay apps) that allow
      multiple people to meet up quickly may facilitate group sex. This study was
      therefore undertaken to evaluate group sex among Chinese MSM and to better
      understand factors associated with group sex. METHODS: An online survey was
      conducted from September-October 2014, collecting data on socio-demographics,
      sexual behaviors, use of gay apps and occurrence of group sex among Chinese MSM.
      Univariate and multivariable logistic regressions were used to compare group sex
      and non-group sex participants. RESULTS: Of the 1,424 MSM, the majority were
      under 30 years old (77.5%), unmarried (83.9%), and were gay apps users (57.9%).
      Overall, 141 (9.9%) participants engaged in group sex in the last 12 months.
      Multivariate analyses showed that men living with HIV, engaged in condomless anal
      intercourse with men, and used gay apps were more likely to engage in group sex,
      with adjusted ORs of 3.74 (95% CI 1.92-7.28), 2.88 (95% CI 2.00-4.16) and 1.46
      (95% CI: 1.00-2.13), respectively. Among gay app users, the likelihood of group
      sex increases with the number of sex partners and the number of sex acts with
      partners met through a gay app. CONCLUSIONS: Chinese MSM who engage in group sex
      are also more likely to engage in other risky sexual behaviors, and gay app use
      may facilitate group sex. Further research is needed among MSM who engage in
      group sex in order to target interventions and surveillance.

PMID- 27880822
TI  - Isolation of a Defective Prion Mutant from Natural Scrapie.
AB  - It is widely known that prion strains can mutate in response to modification of
      the replication environment and we have recently reported that prion mutations
      can occur in vitro during amplification of vole-adapted prions by Protein
      Misfolding Cyclic Amplification on bank vole substrate (bvPMCA). Here we
      exploited the high efficiency of prion replication by bvPMCA to study the in
      vitro propagation of natural scrapie isolates. Although in vitro vole-adapted
      PrPSc conformers were usually similar to the sheep counterpart, we repeatedly
      isolated a PrPSc mutant exclusively when starting from extremely diluted seeds of
      a single sheep isolate. The mutant and faithful PrPSc conformers showed to be
      efficiently autocatalytic in vitro and were characterized by different PrP
      protease resistant cores, spanning aa ~155-231 and ~80-231 respectively, and by
      different conformational stabilities. The two conformers could thus be seen as
      different bona fide PrPSc types, putatively accounting for prion populations with
      different biological properties. Indeed, once inoculated in bank vole the
      faithful conformer was competent for in vivo replication while the mutant was
      unable to infect voles, de facto behaving like a defective prion mutant. Overall,
      our findings confirm that prions can adapt and evolve in the new replication
      environments and that the starting population size can affect their evolutionary
      landscape, at least in vitro. Furthermore, we report the first example of
      "authentic" defective prion mutant, composed of brain-derived PrPC and
      originating from a natural scrapie isolate. Our results clearly indicate that the
      defective mutant lacks of some structural characteristics, that presumably
      involve the central region ~90-155, critical for infectivity but not for in vitro
      replication. Finally, we propose a molecular mechanism able to account for the
      discordant in vitro and in vivo behavior, suggesting possible new paths for
      investigating the molecular bases of prion infectivity.

PMID- 27880825
TI  - Can Simple Transmission Chains Foster Collective Intelligence in Binary-Choice
      Tasks?
AB  - In many social systems, groups of individuals can find remarkably efficient
      solutions to complex cognitive problems, sometimes even outperforming a single
      expert. The success of the group, however, crucially depends on how the judgments
      of the group members are aggregated to produce the collective answer. A large
      variety of such aggregation methods have been described in the literature, such
      as averaging the independent judgments, relying on the majority or setting up a
      group discussion. In the present work, we introduce a novel approach for
      aggregating judgments-the transmission chain-which has not yet been consistently
      evaluated in the context of collective intelligence. In a transmission chain, all
      group members have access to a unique collective solution and can improve it
      sequentially. Over repeated improvements, the collective solution that emerges
      reflects the judgments of every group members. We address the question of whether
      such a transmission chain can foster collective intelligence for binary-choice
      problems. In a series of numerical simulations, we explore the impact of various
      factors on the performance of the transmission chain, such as the group size, the
      model parameters, and the structure of the population. The performance of this
      method is compared to those of the majority rule and the confidence-weighted
      majority. Finally, we rely on two existing datasets of individuals performing a
      series of binary decisions to evaluate the expected performances of the three
      methods empirically. We find that the parameter space where the transmission
      chain has the best performance rarely appears in real datasets. We conclude that
      the transmission chain is best suited for other types of problems, such as those
      that have cumulative properties.

PMID- 27880827
TI  - Correction: E2F1 and TFDP1 Regulate PITX1 Expression in Normal and Osteoarthritic
      Articular Chondrocytes.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0165951.].

PMID- 27880824
TI  - Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a
      Polynuclear Pd-Spermine Agent.
AB  - The present work is aimed at evaluating the antitumour properties of a Pd(II)
      dinuclear complex with the biogenic polyamine spermine, by investigating: i) the
      anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with
      spermine (Pd2Spm); ii) the anti-proliferative activity of Pd2Spm against a triple
      negative human breast carcinoma (MDA-MB-231); and finally iii) the putative
      interaction mediated by combination of Pd2Spm with Docetaxel. Anti-invasive (anti
      angiogenic and anti-migratory) as well as anti-proliferative capacities were
      assessed, for different combination schemes and drug exposure times, using the
      CAM assay and VEGFR2 activity measurement, the MatrigelTM method and the SRB
      proliferation test. The results thus obtained evidence the ability of Pd2Spm to
      restrict angiogenesis and cell migration: Pd2Spm induced a marked inhibition of
      migration (43.8+/-12.2%), and a higher inhibition of angiogenesis (81.8+/-4.4%
      for total length values, at 4 MUM) as compared to DTX at the clinical dosage 4x10
      2 MUM (26.4+/-14.4%; n = 4 to 11). Combination of Pd2Spm/DTX was more effective
      as anti-invasive and anti-proliferative than DTX or Pd2Spm in sole
      administration, which is compatible with the occurrence of synergism: for the
      anti-angiogenic effect, IC50(Pd2Spm/DTX) = 0.5/0.5x10-2 MUM vs IC50(DTX) = 1.7x10
      2 MUM and IC50(Pd2Spm) = 1.6 MUM. In conclusion, the reported effects of Pd2Spm
      on angiogenesis, migration and proliferation showed that this compound is a
      promising therapeutic agent against this type of breast cancer. Moreover,
      combined administration of Pd2Spm and DTX was found to trigger a substantial
      synergetic effect regarding angiogenesis inhibition as well as anti-migratory and
      anti-proliferative activities reinforcing the putative use of Pd(II) complexes in
      chemotherapeutic regimens. This is a significant outcome, aiming at the
      application of these combined strategies towards metastatic breast cancer (or
      other type of resistant cancers), justifying further studies that include pre
      clinical trials.

PMID- 27880826
TI  - Social Monitoring Matters for Deterring Social Deviance in Stable but Not Mobile
      Socio-Ecological Contexts.
AB  - Previous research suggests that reputational concerns can incentivize cooperation
      and deter socially deviant behavior. The current research showed that social
      monitoring of information that has the potential to damage one's reputation has
      differential effects on deviant behavior in social-ecological environments that
      vary in level of mobility. Study 1 showed that residentially stable cities that
      employed more journalists-who can be regarded as social monitoring agents in a
      community-tended to have lower rates of violent crime than residentially stable
      cities that employed fewer journalists; by contrast, in residentially mobile
      cities, violent crime rates did not vary as a function of the number of
      journalists employed. In Study 2, we found that individual differences in
      perceptions of relational mobility moderated the effects of social monitoring on
      cheating in a die-under-cup game. Specifically, social monitoring cues reduced
      the likelihood of cheating but only among participants who perceived their
      immediate social environment to be low in relational mobility. The same results
      were replicated in Study 3, an experiment in which participants' perception of
      relational mobility was manipulated before completing an online maze game that
      allowed them to earn extra cash. In the low mobility condition, the percentage of
      participants who continued working on the mazes after reaching the time limit
      decreased as a function of social monitoring; however, this pattern was not
      observed in the high mobility condition. Together, our findings suggest that
      socioecological context matters for understanding effective mechanisms of social
      control.

PMID- 27880828
TI  - Metabolic Health in Relation to Body Size: Changes in Prevalence over Time
      between 1997-99 and 2008-11 in Germany.
AB  - OBJECTIVE: The study examined potential changes in the proportion of metabolic
      health according to body size categories over time and across strata of sex and
      age, varying definitions of metabolic health. METHODS: We analysed data from
      national health interview and examination surveys 1997-99 and 2008-11 for adults
      aged 18-79 years (GNHIES98: N = 6,565; DEGS1: 6,860). Metabolic health as defined
      by ATPIII criteria was examined across body mass index categories. The Plourde
      and Karelis criteria were applied in relation to abdominal obesity. RESULTS:
      Proportions of adults with metabolic health by body size categories were largely
      stable over time, except for an increasing proportion of metabolically healthy
      persons with pre-obesity and metabolically healthy women without abdominal
      obesity. In both surveys proportions of adults meeting ATPIII criteria ranged
      from approximately 30% among men and women with obesity, to about two thirds of
      those with pre-obesity to about 93% among those with normal weight. According to
      Plourde and Karelis criteria proportions ranged from almost 30% among men and
      women without abdominal obesity to less than 10% among those with abdominal
      obesity. Proportions were consistently higher among younger than older age groups
      and less consistently higher among women than men. CONCLUSIONS: Proportions of
      adults with metabolic health by body size categories were largely stable over
      time, except for an increasing proportion of metabolically healthy women without
      abdominal obesity. There is no evidence that metabolic health among adults with
      obesity increased in Germany over a period of ten years.

PMID- 27880829
TI  - Interleukin-15 (IL-15) Strongly Correlates with Increasing HIV-1 Viremia and
      Markers of Inflammation.
AB  - OBJECTIVE: IL-15 has been postulated to play an important role in HIV-1
      infection, yet there are conflicting reports regarding its expression levels in
      these patients. We sought to measure the level of IL-15 in a large, well
      characterised cohort of HIV-1 infected patients and correlate this with well
      known markers of inflammation, including CRP, D-dimer, sCD163 and sCD14. DESIGN
      AND METHODS: IL-15 levels were measured in 501 people (460 patients with HIV-1
      infection and 41 uninfected controls). The HIV-1 infected patients were divided
      into 4 groups based on viral load: <50 copies/ml, 51-10,000 copies/ml, 10,001
      100,000 copies/ml and >100,000 copies/ml. The Mann Whitney test (non-parametric)
      was used to identify significant relationships between different patient groups.
      RESULTS: IL-15 levels were significantly higher in patients with viral loads
      >100,000 copies/ml (3.02 +/- 1.53 pg/ml) compared to both uninfected controls
      (1.69 +/- 0.37 pg/ml, p<0.001) or patients with a viral load <50 copies/ml (1.59
      +/- 0.40 pg/ml (p<0.001). There was a significant correlation between HIV-1
      viremia and IL-15 levels (Spearman r = 0.54, p<0.001) and between CD4+ T cell
      counts and IL-15 levels (Spearman r = -0.56, p<0.001). CONCLUSIONS: IL-15 levels
      are significantly elevated in HIV-1 infected patients with viral loads >100,000
      copies/ml compared to uninfected controls, with a significant direct correlation
      noted between IL-15 and HIV-1 viremia and an inverse correlation between IL-15
      levels and CD4+ T cell counts. These data support a potential role for IL-15 in
      the pathogenesis of HIV-associated immune activation.

PMID- 27880830
TI  - Synonymous Co-Variation across the E1/E2 Gene Junction of Hepatitis C Virus
      Defines Virion Fitness.
AB  - Hepatitis C virus is a positive-sense single-stranded RNA virus. The gene
      junction partitioning the viral glycoproteins E1 and E2 displays concurrent
      sequence evolution with the 3'-end of E1 highly conserved and the 5'-end of E2
      highly heterogeneous. This gene junction is also believed to contain structured
      RNA elements, with a growing body of evidence suggesting that such structures can
      act as an additional level of viral replication and transcriptional control. We
      have previously used ultradeep pyrosequencing to analyze an amplicon library
      spanning the E1/E2 gene junction from a treatment naive patient where samples
      were collected over 10 years of chronic HCV infection. During this timeframe
      maintenance of an in-frame insertion, recombination and humoral immune targeting
      of discrete virus sub-populations was reported. In the current study, we present
      evidence of epistatic evolution across the E1/E2 gene junction and observe the
      development of co-varying networks of codons set against a background of a
      complex virome with periodic shifts in population dominance. Overtime, the number
      of codons actively mutating decreases for all virus groupings. We identify strong
      synonymous co-variation between codon sites in a group of sequences harbouring a
      3 bp in-frame insertion and propose that synonymous mutation acts to stabilize
      the RNA structural backbone.

PMID- 27880831
TI  - Assessment of Homonymous Recurrent Inhibition during Voluntary Contraction by
      Conditioning Nerve Stimulation.
AB  - In humans, the amount of spinal homonymous recurrent inhibition during voluntary
      contraction is usually assessed by using a peripheral nerve stimulation paradigm.
      This method consists of conditioning the maximal M-wave (SM stimulus) with prior
      reflex stimulation (S1), with 10 ms inter-stimulus interval (ISI). The decrease
      observed between unconditioned (S1 only) and conditioned (S1+SM) reflex size is
      then attributed to recurrent inhibition. However, during a voluntary contraction,
      a superimposed SM stimulation leads to a maximal M-wave followed by a voluntary
      (V) wave at similar latency than the H-reflex. This wave can therefore interfere
      with the conditioned H-reflex when two different stimulation intensities are used
      (S1 and SM), leading to misinterpretation of the data. The aim of the present
      study was to assess if conditioning V-wave response instead of H-reflex, by
      applying SM for both stimuli (test and conditioning), can be used as an index of
      recurrent inhibition. Conditioned and unconditioned responses of soleus and
      medial gastrocnemius muscles were recorded in twelve subjects at 25% and at 50%
      of maximal voluntary contraction at the usual ISI of 10 ms and an optimal inter
      stimulus of 15 ms determined upon M- and V-wave latencies. Conditioned H-reflex
      (obtained with S1+SM paradigm) was significantly lower than the unconditioned by
      ~30% on average, meaning that the amount of inhibition was 70%. This amount of
      recurrent inhibition was significantly lower at higher force level with both
      methods. Regardless of the level of force or the conditioning ISI, results
      obtained with V-wave conditioning (SM+SM) were similar at both force levels,
      linearly correlated and proportional to those obtained with H conditioning. Then,
      V-wave conditioning appears to be a reliable index of homonymous recurrent
      inhibition during voluntary contraction.

PMID- 27880832
TI  - Chronic Low-Calorie Sweetener Use and Risk of Abdominal Obesity among Older
      Adults: A Cohort Study.
AB  - INTRODUCTION: Low-calorie sweetener use for weight control has come under
      increasing scrutiny as obesity, especially abdominal obesity, remain entrenched
      despite substantial low-calorie sweetener use. We evaluated whether chronic low
      calorie sweetener use is a risk factor for abdominal obesity. PARTICIPANTS AND
      METHODS: We used 8268 anthropometric measurements and 3096 food diary records
      with detailed information on low-calorie sweetener consumption in all food
      products, from 1454 participants (741 men, 713 women) in the Baltimore
      Longitudinal Study of Aging collected from 1984 to 2012 with median follow-up of
      10 years (range: 0-28 years). At baseline, 785 were low-calorie sweetener non
      users (51.7% men) and 669 participants were low-calorie sweetener users (50.1%
      men). Time-varying low-calorie sweetener use was operationalized as the
      proportion of visits since baseline at which low-calorie sweetener use was
      reported. We used marginal structural models to determine the association between
      baseline and time-varying low-calorie sweetener use with longitudinal outcomes
      body mass index, waist circumference, obesity and abdominal obesity-with outcome
      status assessed at the visit following low-calorie sweetener ascertainment to
      minimize the potential for reverse causality. All models were adjusted for year
      of visit, age, sex, age by sex interaction, race, current smoking status, dietary
      intake (caffeine, fructose, protein, carbohydrate, and fat), physical activity,
      diabetes status, and Dietary Approaches to Stop Hypertension score as
      confounders. RESULTS: With median follow-up of 10 years, low-calorie sweetener
      users had 0.80 kg/m2 higher body mass index (95% confidence interval [CI], 0.17
      1.44), 2.6 cm larger waist circumference (95% CI, 0.71-4.39), 36.7% higher
      prevalence (prevalence ratio = 1.37; 95% CI, 1.10-1.69) and 53% higher incidence
      (hazard ratio = 1.53; 95% CI 1.10-2.12) of abdominal obesity than low-calorie
      sweetener non-users. CONCLUSIONS: Low-calorie sweetener use is independently
      associated with heavier relative weight, a larger waist, and a higher prevalence
      and incidence of abdominal obesity suggesting that low-calorie sweetener use may
      not be an effective means of weight control.

PMID- 27880833
TI  - Prioritizing Risk in Preparation for a Demonstration Project: A Mixed Methods
      Feasibility Study of Oral Pre-Exposure Prophylaxis (PREP) among Female Sex
      Workers in South India.
AB  - BACKGROUND: HIV prevalence among female sex workers (FSWs) in India remains well
      above the national average. Pre-exposure prophylaxis (PrEP), a new HIV prevention
      technology, may help to reduce HIV incidence, but there is a dearth of research
      that can inform the potential scale-up of PrEP in India. In partnership with
      Ashodaya Samithi, a local sex worker collective, we conducted a feasibility study
      to assess acceptance of a planned PrEP demonstration project, willingness to use
      PrEP, and recommendations for project roll-out among FSWs in southern Karnataka.
      METHODS: From January-April 2015, 6 focus group discussions, 47 in-depth
      interviews, and 427 interviewer-administered questionnaires were completed by
      female sex workers. All participants were 18 years of age or older and practiced
      sex work. Qualitative data were coded for key themes and emergent categories.
      Univariate descriptive analysis was employed to summarise the quantitative data.
      RESULTS: Qualitative. PrEP was described as an exciting new prevention technology
      that places control in the hands of FSWs and provides a "double safety" in
      combination with condom use. Participants expressed agreement that women who may
      experience more HIV risk in their occupational environments should be prioritized
      for enrollment into a demonstration project. Quantitative. 406 participants (95%)
      expressed interest in PrEP. Participants prioritized the inclusion of FSWs under
      the age of 25 (79%), those who do not use condoms when clients offer more money
      (58%), who do not consistently use condoms with regular partners (57%), who drink
      alcohol regularly (49%), and who do not use condoms consistently with clients
      (48%). DISCUSSION: This feasibility study indicated strong interest in PrEP and a
      desire to move forward with the demonstration project. Participants expressed
      their responses in terms of public health discourses surrounding risk, pointing
      to the importance of situating PrEP scale up within the trusted spaces of
      community-based organizations as a means of supporting PrEP uptake and adherence.

PMID- 27880834
TI  - Overexpressed Proteins in Hypervirulent Clade 8 and Clade 6 Strains of
      Escherichia coli O157:H7 Compared to E. coli O157:H7 EDL933 Clade 3 Strain.
AB  - Escherichia coli O157:H7 is responsible for severe diarrhea and hemolytic uremic
      syndrome (HUS), and predominantly affects children under 5 years. The major
      virulence traits are Shiga toxins, necessary to develop HUS and the Type III
      Secretion System (T3SS) through which bacteria translocate effector proteins
      directly into the host cell. By SNPs typing, E. coli O157:H7 was separated into
      nine different clades. Clade 8 and clade 6 strains were more frequently
      associated with severe disease and HUS. In this study, we aimed to identify
      differentially expressed proteins in two strains of E. coli O157:H7 (clade 8 and
      clade 6), obtained from cattle and compared them with the well characterized
      reference EDL933 strain (clade 3). Clade 8 and clade 6 strains show enhanced
      pathogenicity in a mouse model and virulence-related properties. Proteins were
      extracted and analyzed using the TMT-6plex labeling strategy associated with two
      dimensional liquid chromatography and mass spectrometry in tandem. We detected
      2241 proteins in the cell extract and 1787 proteins in the culture supernatants.
      Attention was focused on the proteins related to virulence, overexpressed in
      clade 6 and 8 strains compared to EDL933 strain. The proteins relevant
      overexpressed in clade 8 strain were the curli protein CsgC, a transcriptional
      activator (PchE), phage proteins, Stx2, FlgM and FlgD, a dienelactone hydrolase,
      CheW and CheY, and the SPATE protease EspP. For clade 6 strain, a high
      overexpression of phage proteins was detected, mostly from Stx2 encoding phage,
      including Stx2, flagellin and the protease TagA, EDL933_p0016, dienelactone
      hydrolase, and Haemolysin A, amongst others with unknown function. Some of these
      proteins were analyzed by RT-qPCR to corroborate the proteomic data. Clade 6 and
      clade 8 strains showed enhanced transcription of 10 out of 12 genes compared to
      EDL933. These results may provide new insights in E. coli O157:H7 mechanisms of
      pathogenesis.

PMID- 27880836
TI  - Towards the Automatic Classification of Avian Flight Calls for Bioacoustic
      Monitoring.
AB  - Automatic classification of animal vocalizations has great potential to enhance
      the monitoring of species movements and behaviors. This is particularly true for
      monitoring nocturnal bird migration, where automated classification of migrants'
      flight calls could yield new biological insights and conservation applications
      for birds that vocalize during migration. In this paper we investigate the
      automatic classification of bird species from flight calls, and in particular the
      relationship between two different problem formulations commonly found in the
      literature: classifying a short clip containing one of a fixed set of known
      species (N-class problem) and the continuous monitoring problem, the latter of
      which is relevant to migration monitoring. We implemented a state-of-the-art
      audio classification model based on unsupervised feature learning and evaluated
      it on three novel datasets, one for studying the N-class problem including over
      5000 flight calls from 43 different species, and two realistic datasets for
      studying the monitoring scenario comprising hundreds of thousands of audio clips
      that were compiled by means of remote acoustic sensors deployed in the field
      during two migration seasons. We show that the model achieves high accuracy when
      classifying a clip to one of N known species, even for a large number of species.
      In contrast, the model does not perform as well in the continuous monitoring
      case. Through a detailed error analysis (that included full expert review of
      false positives and negatives) we show the model is confounded by varying
      background noise conditions and previously unseen vocalizations. We also show
      that the model needs to be parameterized and benchmarked differently for the
      continuous monitoring scenario. Finally, we show that despite the reduced
      performance, given the right conditions the model can still characterize the
      migration pattern of a specific species. The paper concludes with directions for
      future research.

PMID- 27880835
TI  - Built Environment, Selected Risk Factors and Major Cardiovascular Disease
      Outcomes: A Systematic Review.
AB  - INTRODUCTION: Built environment attributes have been linked to cardiovascular
      disease (CVD) risk. Therefore, identifying built environment attributes that are
      associated with CVD risk is relevant for facilitating effective public health
      interventions. OBJECTIVE: To conduct a systematic review of literature to examine
      the influence of built environmental attributes on CVD risks. DATA SOURCE:
      Multiple database searches including Science direct, CINAHL, Masterfile Premier,
      EBSCO and manual scan of reference lists were conducted. INCLUSION CRITERIA:
      Studies published in English between 2005 and April 2015 were included if they
      assessed one or more of the neighborhood environmental attributes in relation
      with any major CVD outcomes and selected risk factors among adults. DATA
      EXTRACTION: Author(s), country/city, sex, age, sample size, study design, tool
      used to measure neighborhood environment, exposure and outcome assessments and
      associations were extracted from eligible studies. RESULTS: Eighteen studies met
      the inclusion criteria. Most studies used both cross-sectional design and
      Geographic Information System (GIS) to assess the neighborhood environmental
      attributes. Neighborhood environmental attributes were significantly associated
      with CVD risk and CVD outcomes in the expected direction. Residential density,
      safety from traffic, recreation facilities, street connectivity and high walkable
      environment were associated with physical activity. High walkable environment,
      fast food restaurants, supermarket/grocery stores were associated with blood
      pressure, body mass index, diabetes mellitus and metabolic syndrome. High density
      traffic, road proximity and fast food restaurants were associated with CVDs
      outcomes. CONCLUSION: This study confirms the relationship between neighborhood
      environment attributes and CVDs and risk factors. Prevention programs should
      account for neighborhood environmental attributes in the communities where people
      live.

PMID- 27880837
TI  - Rice Yield and the Fate of Fertilizer Nitrogen as Affected by Addition of
      Earthworm Casts Collected from Oilseed Rape Fields: A Pot Experiment.
AB  - The mechanism associated with improvement of soil nutritional status by oilseed
      rape crop, leading to better performance of rice crop, in rice-oilseed rape
      cropping systems is little known. The present study was aimed to test the
      hypothesis that earthworm casts produced during oilseed rape-growing season have
      positive effects on grain yield and fertilizer nitrogen (N) utilization in the
      subsequent flooded rice crop. A 15N-tracing pot experiment was conducted to
      determine the effects of earthworm casts collected from oilseed rape fields on
      yield attributes in rice and the fate of fertilizer N. Soil treated with
      earthworm casts (soil: earthworm casts = 4: 1, w/w) (EC1) produced 39% higher
      grain yield than soil only (EC0). EC1 had 18% more panicle number and 10% higher
      spikelet filling percentage than EC0. Aboveground biomass and harvest index were
      higher in EC1 than in EC0 by 20% and 15%, respectively. SPAD values in flag
      leaves were 10% and 22% higher under EC1 than EC0 at 15 and 20 days after
      heading, respectively. EC1 had 19% higher total N uptake and 18% higher
      physiological N-use efficiency than EC0. These positive effects of earthworm
      casts on yield attributes offset negative effects of decreasing N rate from 0.74
      g pot-1 (equivalent to the recommended field rate of 150 kg ha-1) to 0.44 g pot-1
      (equivalent to 60% of the recommended rate). Fertilizer N retention rate was 7%
      higher while fertilizer N loss rate was 6% lower in EC1 than in EC0. Our study
      suggests that earthworm casts produced during oilseed rape-growing season are
      expected to have the following benefits on the subsequent flooded rice system:
      (1) improving growth and physiological processes in rice plants and consequently
      increasing rice grain yield, and (2) increasing fertilizer N retention rate and
      hence decreasing fertilizer N loss rate and reducing environmental risk.

PMID- 27880839
TI  - Composite Sickles and Cereal Harvesting Methods at 23,000-Years-Old Ohalo II,
      Israel.
AB  - Use-wear analysis of five glossed flint blades found at Ohalo II, a 23,000-years
      old fisher-hunter-gatherers' camp on the shore of the Sea of Galilee, Northern
      Israel, provides the earliest evidence for the use of composite cereal harvesting
      tools. The wear traces indicate that tools were used for harvesting near-ripe
      semi-green wild cereals, shortly before grains are ripe and disperse naturally.
      The studied tools were not used intensively, and they reflect two harvesting
      modes: flint knives held by hand and inserts hafted in a handle. The finds shed
      new light on cereal harvesting techniques some 8,000 years before the Natufian
      and 12,000 years before the establishment of sedentary farming communities in the
      Near East. Furthermore, the new finds accord well with evidence for the earliest
      ever cereal cultivation at the site and the use of stone-made grinding
      implements.

PMID- 27880838
TI  - Detection of Endotoxin Contamination of Graphene Based Materials Using the TNF
      alpha Expression Test and Guidelines for Endotoxin-Free Graphene Oxide
      Production.
AB  - Nanomaterials may be contaminated with bacterial endotoxin during production and
      handling, which may confound toxicological testing of these materials, not least
      when assessing for immunotoxicity. In the present study, we evaluated the
      conventional Limulus amebocyte lysate (LAL) assay for endotoxin detection in
      graphene based material (GBM) samples, including graphene oxide (GO) and few
      layered graphene (FLG). Our results showed that some GO samples interfered with
      various formats of the LAL assay. To overcome this problem, we developed a TNF
      alpha expression test (TET) using primary human monocyte-derived macrophages
      incubated in the presence or absence of the endotoxin inhibitor, polymyxin B
      sulfate, and found that this assay, performed with non-cytotoxic doses of the GBM
      samples, enabled unequivocal detection of endotoxin with a sensitivity that is
      comparable to the LAL assay. FLG also triggered TNF-alpha production in the
      presence of the LPS inhibitor, pointing to an intrinsic pro-inflammatory effect.
      Finally, we present guidelines for the preparation of endotoxin-free GO,
      validated by using the TET.

PMID- 27880840
TI  - Modelling Carbon Emissions in Calluna vulgaris-Dominated Ecosystems when
      Prescribed Burning and Wildfires Interact.
AB  - A present challenge in fire ecology is to optimize management techniques so that
      ecological services are maximized and C emissions minimized. Here, we modeled the
      effects of different prescribed-burning rotation intervals and wildfires on
      carbon emissions (present and future) in British moorlands. Biomass-accumulation
      curves from four Calluna-dominated ecosystems along a north-south gradient in
      Great Britain were calculated and used within a matrix-model based on Markov
      Chains to calculate above-ground biomass-loads and annual C emissions under
      different prescribed-burning rotation intervals. Additionally, we assessed the
      interaction of these parameters with a decreasing wildfire return intervals. We
      observed that litter accumulation patterns varied between sites. Northern sites
      (colder and wetter) accumulated lower amounts of litter with time than southern
      sites (hotter and drier). The accumulation patterns of the living vegetation
      dominated by Calluna were determined by site-specific conditions. The optimal
      prescribed-burning rotation interval for minimizing annual carbon emissions also
      differed between sites: the optimal rotation interval for northern sites was
      between 30 and 50 years, whereas for southern sites a hump-backed relationship
      was found with the optimal interval either between 8 to 10 years or between 30 to
      50 years. Increasing wildfire frequency interacted with prescribed-burning
      rotation intervals by both increasing C emissions and modifying the optimum
      prescribed-burning interval for minimum C emission. This highlights the
      importance of studying site-specific biomass accumulation patterns with respect
      to environmental conditions for identifying suitable fire-rotation intervals to
      minimize C emissions.

PMID- 27880841
TI  - Association between Maternal Mortality and Cesarean Section: Turkey Experience.
AB  - BACKGROUND: To investigate the cesarean Section (C/S) rates and maternal
      mortality (MM) causes and its relation between 2002 and 2013. METHODS: Data were
      gathered from Turkish Ministry of Health and Istanbul Health Administration. The
      Annual Clinical Reports for 2002-2013 were reviewed and analyzed: C/Ss and
      maternal deaths in women who gave birth >=20 weeks between January 1, 2002, and
      December 31, 2013, in any hospital in Turkey and Istanbul. RESULTS: The major
      causes of MM were hemorrhage (20%), hypertensive disorders (18.2%), embolism
      (10.3%), cardiovascular conditions (9%), infection (8.5%), and other causes
      (10.4%). Overall, the average annual CS delivery rate was 46.4% in Istanbul and
      36.6% in Turkey. There was a significant increase in the CS rates in Istanbul and
      Turkey from 2008 to 2013 relative to those from 2002 to 2007 (p = 0.004). There
      was a statistically significant and inverse relationship (97.2%) between the MMR
      and CS rate from 2002 to 2013 in Turkey (p = 0.001). However, no significant
      relationship was detected between the MMR and CS rate from 2002 to 2013 in
      Istanbul (p > 0.05). There was a significant inverse correlation (66.3%) between
      the CS rate and peripartumhemorrhage in Turkey (p = 0.019) and there was a
      significant inverse correlation (66.5%) between the CS rate and
      peripartumhemorrhage(p = 0.018) in Istanbul between 2007 to 2013. There were no
      significant differences in ante-intrapartum haemorrhage bleeding (p > 0.05) or
      postpartum hemorrhage (p > 0.05) from 2007 to 2013. CONCLUSIONS: This study
      demonstrates that there was a inverse correlation between increased CS and
      maternal mortality rates during the previous decade in Turkey. Although cesarean
      rates increase excessively, it appears that improved health care facilities have
      a positive effect on MMRs in Turkey.

PMID- 27880842
TI  - A New Morphological Type of Volvox from Japanese Large Lakes and Recent
      Divergence of this Type and V. ferrisii in Two Different Freshwater Habitats.
AB  - Volvox sect. Volvox is characterized by having unique morphological
      characteristics, such as thick cytoplasmic bridges between adult somatic cells in
      the spheroids and spiny zygote walls. Species of this section are found from
      various freshwater habitats. Recently, three species of Volvox sect. Volvox
      originating from rice paddies and a marsh were studied taxonomically based on
      molecular and morphological data of cultured materials. However, taxonomic
      studies have not been performed on cultured materials of this section originating
      from large lake water bodies. We studied a new morphological type of Volvox sect.
      Volvox ("Volvox sp. Sagami"), using cultured materials originating from two large
      lakes and a pond in Japan. Volvox sp. Sagami produced monoecious sexual spheroids
      and may represent a new morphological species; it could be clearly distinguished
      from all previously described monoecious species of Volvox sect. Volvox by its
      small number of eggs or zygotes (5-25) in sexual spheroids, with short acute
      spines (up to 3 MUm long) on the zygote walls and elongated anterior somatic
      cells in asexual spheroids. Based on sequences of internal transcribed spacer
      (ITS) regions of nuclear ribosomal DNA (rDNA; ITS-1, 5.8S rDNA and ITS-2) and
      plastid genes, however, the Volvox sp. Sagami lineage and its sister lineage (the
      monoecious species V. ferrisii) showed very small genetic differences, which
      correspond to the variation within a single biological species in other
      volvocalean algae. Since V. ferrisii was different from Volvox sp. Sagami, by
      having approximately 100-200 zygotes in the sexual spheroids and long spines (6
      8.5 MUm long) on the zygote walls, as well as growing in Japanese rice paddies,
      these two morphologically distinct lineages might have diverged rapidly in the
      two different freshwater habitats. In addition, the swimming velocity during
      phototaxis of Volvox sp. Sagami spheroids originating from large lakes was
      significantly higher than that of V. ferrisii originating from rice paddies,
      suggesting adaptation of Volvox sp. Sagami to large water bodies.

PMID- 27880843
TI  - Highly Divergent Clostridium difficile Strains Isolated from the Environment.
AB  - Clostridium difficile is one of the most important human and animal pathogens.
      However, the bacterium is ubiquitous and can be isolated from various sources.
      Here we report the prevalence and characterization of C. difficile in less
      studied environmental samples, puddle water (n = 104) and soil (n = 79). C.
      difficile was detected in 14.4% of puddle water and in 36.7% of soil samples.
      Environmental strains displayed antimicrobial resistance patterns comparable to
      already published data of human and animal isolates. A total of 480 isolates were
      grouped into 34 different PCR ribotypes. More than half of these (52.9%; 18 of
      34) were already described in humans or animals. However, 14 PCR ribotypes were
      new in our PCR ribotype library and all but one were non-toxigenic. The
      multilocus sequence analysis of these new PCR ribotypes revealed that non
      toxigenic environmental isolates are phylogenetically distinct and belong to
      three highly divergent clades, two of which have not been described before. Our
      data suggest that environment is a potential reservoir of genetically diverse
      population of C. difficile.

PMID- 27880844
TI  - Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by
      Interfering with Collagen Metabolism.
AB  - PURPOSE: Therapeutic strategies that modulate ventricular remodeling can be
      useful after acute myocardial infarction (MI). In particular, statins may exert
      effects on molecular pathways involved in collagen metabolism. The aim of this
      study was to determine whether treatment with atorvastatin for 4 weeks would lead
      to changes in collagen metabolism and ventricular remodeling in a rat model of
      MI. METHODS: Male Wistar rats were used in this study. MI was induced in rats by
      ligation of the left anterior descending coronary artery (LAD). Animals were
      randomized into three groups, according to treatment: sham surgery without LAD
      ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day
      for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline
      solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic
      characteristics were obtained by a pressure-volume catheter. Hearts were removed,
      and the left ventricles were subjected to histologic analysis of the extents of
      fibrosis and collagen deposition, as well as the myocyte cross-sectional area.
      Expression levels of mediators involved in collagen metabolism and inflammation
      were also assessed. RESULTS: End-diastolic volume, fibrotic content, and myocyte
      cross-sectional area were significantly reduced in the atorvastatin compared to
      the control group. Atorvastatin modulated expression levels of proteins related
      to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote
      infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by
      lower expression levels of TLR4, IL-1, and NF-kB p50. CONCLUSION: Treatment with
      atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis,
      and left ventricular hypertrophy after MI in rats, perhaps in part through
      effects on collagen metabolism and inflammation. Atorvastatin may be useful for
      limiting ventricular remodeling after myocardial ischemic events.

PMID- 27880845
TI  - Central Sleep Apnoea Is Related to the Severity and Short-Term Prognosis of Acute
      Coronary Syndrome.
AB  - OBJECTIVE: To evaluate the relation of central sleep apnoea (CSA) to the severity
      and short-term prognosis of patients who experience acute coronary syndrome
      (ACS). METHODS: Observational study with cross-sectional and longitudinal
      analyses. Patients acutely admitted to participating hospitals because of ACS
      underwent respiratory polygraphy during the first 24 to 72 h. CSA was defined as
      an apnoea-hypopnoea index (AHI) >15 events*h-1 (>50% of central apnoeas). ACS
      severity (Killip class, ejection fraction, number of diseased vessels and peak
      plasma troponin) was evaluated at baseline, and short-term prognosis (length of
      hospitalization, complications and mortality) was evaluated at discharge.
      RESULTS: A total of 68 CSA patients (AHI 31+/-18 events*h-1, 64+/-12 years, 87%
      males) and 92 controls (AHI 7+/-5 events*h-1, 62+/-12 years, 84% males) were
      included in the analyses. After adjusting for age, body mass index, hypertension
      and smoking status, patients diagnosed with CSA spent more days in the coronary
      unit compared with controls (3.7+/-2.9 vs. 1.5+/-1.7; p<0.001) and had a worse
      Killip class (Killip I: 16% vs. 96%; p<0.001). No differences were observed in
      ejection fraction estimates. CONCLUSIONS: CSA patients exhibited increased ACS
      severity as indicated by their Killip classification. These patients had a worse
      prognosis, with longer lengths of stay in the coronary care units. Our results
      highlight the relevance of CSA in patients suffering ACS episodes and suggest
      that diagnosing CSA may be a useful strategy to improve the management of certain
      ACS patients.

PMID- 27880846
TI  - Potential Impacts of Climate Change on Native Plant Distributions in the Falkland
      Islands.
AB  - The Falkland Islands are predicted to experience up to 2.2 degrees C rise in mean
      annual temperature over the coming century, greater than four times the rate over
      the last century. Our study investigates likely vulnerabilities of a suite of
      range-restricted species whose distributions are associated with archipelago-wide
      climatic variation. We used present day climate maps calibrated using local
      weather data, 2020-2080 climate predictions from regional climate models, non
      climate variables derived from a digital terrain model and a comprehensive
      database on local plant distributions. Weighted mean ensemble models were
      produced to assess changes in range sizes and overlaps between the current range
      and protected areas network. Target species included three globally threatened
      Falkland endemics, Nassauvia falklandica, Nastanthus falklandicus and Plantago
      moorei; and two nationally threatened species, Acaena antarctica and Blechnum
      cordatum. Our research demonstrates that temperature increases predicted for the
      next century have the potential to significantly alter plant distributions across
      the Falklands. Upland species, in particular, were found to be highly vulnerable
      to climate change impacts. No known locations of target upland species or the
      southwestern species Plantago moorei are predicted to remain environmentally
      suitable in the face of predicted climate change. We identify potential refugia
      for these species and associated gaps in the current protected areas network.
      Species currently restricted to the milder western parts of the archipelago are
      broadly predicted to expand their ranges under warmer temperatures. Our results
      emphasise the importance of implementing suitable adaptation strategies to offset
      climate change impacts, particularly site management. There is an urgent need for
      long-term monitoring and artificial warming experiments; the results of this
      study will inform the selection of the most suitable locations for these. Results
      are also helping inform management recommendations for the Falkland Islands
      Government who seek to better conserve their biodiversity and meet commitments to
      multi-lateral environmental agreements.

PMID- 27880848
TI  - Genome-Scale Assessment of Age-Related DNA Methylation Changes in Mouse
      Spermatozoa.
AB  - DNA methylation plays important roles in the production and functioning of
      spermatozoa. Recent studies have suggested that DNA methylation patterns in
      spermatozoa can change with age, but the regions susceptible to age-related
      methylation changes remain to be fully elucidated. In this study, we conducted
      genome-scale DNA methylation profiling of spermatozoa obtained from C57BL/6N mice
      at 8 weeks (8w), 18 weeks (18w) and 17 months of age (17m). There was no
      substantial difference in the global DNA methylation patterns between 18w and 17m
      samples except for a slight increase of methylation levels in long interspersed
      nuclear elements in the 17m samples. We found that maternally methylated
      imprinting control regions (mICRs) and spermatogenesis-related gene promoters had
      5-10% higher methylation levels in 8w samples than in 18w or 17m samples.
      Analysis of individual sequence reads suggested that these regions were fully
      methylated (80-100%) in a subset of 8w spermatozoa. These regions are also known
      to be highly methylated in a subset of postnatal spermatogonia, which might be
      the source of the increased DNA methylation in 8w spermatozoa. Another possible
      source was contamination by somatic cells. Although we carefully purified the
      spermatozoa, it was difficult to completely exclude the possibility of somatic
      cell contamination. Further studies are needed to clarify the source of the small
      increase in DNA methylation in the 8w samples. Overall, our findings suggest that
      DNA methylation patterns in mouse spermatozoa are relatively stable throughout
      reproductive life.

PMID- 27880847
TI  - Activation of Both the Calpain and Ubiquitin-Proteasome Systems Contributes to
      Septic Cardiomyopathy through Dystrophin Loss/Disruption and mTOR Inhibition.
AB  - Cardiac dysfunction caused by the impairment of myocardial contractility has been
      recognized as an important factor contributing to the high mortality in sepsis.
      Calpain activation in the heart takes place in response to increased
      intracellular calcium influx resulting in proteolysis of structural and
      contractile proteins with subsequent myocardial dysfunction. The purpose of the
      present study was to test the hypothesis that increased levels of calpain in the
      septic heart leads to disruption of structural and contractile proteins and that
      administration of calpain inhibitor-1 (N-acetyl-leucinyl-leucinyl-norleucinal
      (ALLN)) after sepsis induced by cecal ligation and puncture prevents cardiac
      protein degradation. We also tested the hypothesis that calpain plays a role in
      the modulation of protein synthesis/degradation through the activation of
      proteasome-dependent proteolysis and inhibition of the mTOR pathway. Severe
      sepsis significantly increased heart calpain-1 levels and promoted ubiquitin and
      Pa28beta over-expression with a reduction in the mTOR levels. In addition, sepsis
      reduced the expression of structural proteins dystrophin and beta-dystroglycan as
      well as the contractile proteins actin and myosin. ALLN administration prevented
      sepsis-induced increases in calpain and ubiquitin levels in the heart, which
      resulted in decreased of structural and contractile proteins degradation and
      basal mTOR expression levels were re-established. Our results support the concept
      that increased calpain concentrations may be part of an important mechanism of
      sepsis-induced cardiac muscle proteolysis.

PMID- 27880850
TI  - Visual Enhancement of Illusory Phenomenal Accents in Non-Isochronous Auditory
      Rhythms.
AB  - Musical rhythms encompass temporal patterns that often yield regular metrical
      accents (e.g., a beat). There have been mixed results regarding perception as a
      function of metrical saliency, namely, whether sensitivity to a deviant was
      greater in metrically stronger or weaker positions. Besides, effects of metrical
      position have not been examined in non-isochronous rhythms, or with respect to
      multisensory influences. This study was concerned with two main issues: (1) In
      non-isochronous auditory rhythms with clear metrical accents, how would
      sensitivity to a deviant be modulated by metrical positions? (2) Would the
      effects be enhanced by multisensory information? Participants listened to
      strongly metrical rhythms with or without watching a point-light figure dance to
      the rhythm in the same meter, and detected a slight loudness increment. Both
      conditions were presented with or without an auditory interference that served to
      impair auditory metrical perception. Sensitivity to a deviant was found greater
      in weak beat than in strong beat positions, consistent with the Predictive Coding
      hypothesis and the idea of metrically induced illusory phenomenal accents. The
      visual rhythm of dance hindered auditory detection, but more so when the latter
      was itself less impaired. This pattern suggested that the visual and auditory
      rhythms were perceptually integrated to reinforce metrical accentuation, yielding
      more illusory phenomenal accents and thus lower sensitivity to deviants, in a
      manner consistent with the principle of inverse effectiveness. Results were
      discussed in the predictive framework for multisensory rhythms involving observed
      movements and possible mediation of the motor system.

PMID- 27880849
TI  - Loading Patterns of the Posterior Cruciate Ligament in the Healthy Knee: A
      Systematic Review.
AB  - BACKGROUND: The posterior cruciate ligament (PCL) is the strongest ligament of
      the knee, serving as one of the major passive stabilizers of the tibio-femoral
      joint. However, despite a number of experimental and modelling approaches to
      understand the kinematics and kinetics of the ligament, the normal loading
      conditions of the PCL and its functional bundles are still controversially
      discussed. OBJECTIVES: This study aimed to generate science-based evidence for
      understanding the functional loading of the PCL, including the anterolateral and
      posteromedial bundles, in the healthy knee joint through systematic review and
      statistical analysis of the literature. DATA SOURCES: MEDLINE, EMBASE and
      CENTRAL. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Databases were searched for
      articles containing any numerical strain or force data on the healthy PCL and its
      functional bundles. Studied activities were as follows: passive flexion, flexion
      under 100N and 134N posterior tibial load, walking, stair ascent and descent,
      body-weight squatting and forward lunge. METHOD: Statistical analysis was
      performed on the reported load data, which was weighted according to the number
      of knees tested to extract average strain and force trends of the PCL and
      identify deviations from the norms. RESULTS: From the 3577 articles retrieved by
      the initial electronic search, only 66 met all inclusion criteria. The results
      obtained by aggregating data reported in the eligible studies indicate that the
      loading patterns of the PCL vary with activity type, knee flexion angle, but
      importantly also the technique used for assessment. Moreover, different fibres of
      the PCL exhibit different strain patterns during knee flexion, with higher strain
      magnitudes reported in the anterolateral bundle. While during passive flexion the
      posteromedial bundle is either lax or very slightly elongated, it experiences
      higher strain levels during forward lunge and has a synergetic relationship with
      the anterolateral bundle. The strain patterns obtained for virtual fibres that
      connect the origin and insertion of the bundles in a straight line show similar
      trends to those of the real bundles but with different magnitudes. CONCLUSION:
      This review represents what is now the best available understanding of the
      biomechanics of the PCL, and may help to improve programs for injury prevention,
      diagnosis methods as well as reconstruction and rehabilitation techniques.

PMID- 27880851
TI  - Diagnostic Utility of Pleural Fluid Cell Block versus Pleural Biopsy Collected by
      Flex-Rigid Pleuroscopy for Malignant Pleural Disease: A Single Center
      Retrospective Analysis.
AB  - BACKGROUND: Some trials recently demonstrated the benefit of targeted treatment
      for malignant disease; therefore, adequate tissues are needed to detect the
      targeted gene. Pleural biopsy using flex-rigid pleuroscopy and pleural effusion
      cell block analysis are both useful for diagnosis of malignancy and obtaining
      adequate samples. The purpose of our study was to compare the diagnostic utility
      between the two methods among patients with malignant pleural disease with
      effusion. METHODS: Data from patients who underwent flex-rigid pleuroscopy for
      diagnosis of pleural effusion suspicious for malignancy at the National Cancer
      Center Hospital, Japan between April 2011 and June 2014 were retrospectively
      reviewed. All procedures were performed under local anesthesia. At least 150 mL
      of pleural fluid was collected by pleuroscopy, followed by pleural biopsies from
      the abnormal site. RESULTS: Thirty-five patients who were finally diagnosed as
      malignant pleural disease were included in this study. Final diagnoses of
      malignancy were 24 adenocarcinoma, 1 combined adeno-small cell carcinoma, and 7
      malignant pleural mesothelioma (MPM), and 3 metastatic breast cancer. The
      diagnostic yield was significantly higher by pleural biopsy than by cell block
      [94.2% (33/35) vs. 71.4% (25/35); p = 0.008]. All patients with positive results
      on cell block also had positive results on pleural biopsy. Eight patients with
      negative results on cell block had positive results on pleural biopsy (lung
      adenocarcinoma in 4, sarcomatoid MPM in 3, and metastatic breast cancer in 1).
      Two patients with negative results on both cell block and pleural biopsy were
      diagnosed was sarcomatoid MPM by computed tomography-guided needle biopsy and
      epithelioid MPM by autopsy. CONCLUSION: Pleural biopsy using flex-rigid
      pleuroscopy was efficient in the diagnosis of malignant pleural diseases. Flex
      rigid pleuroscopy with pleural biopsy and pleural effusion cell block analysis
      should be considered as the initial diagnostic approach for malignant pleural
      diseases presenting with effusion.

PMID- 27880853
TI  - Risk of Stroke after Herpes Zoster - Evidence from a German Self-Controlled Case
      Series Study.
AB  - BACKGROUND: Herpes zoster (HZ) is caused by reactivation of the latent varicella
      zoster virus (VZV). A severe complication of HZ is VZV vasculopathy which can
      result in ischemic or hemorrhagic stroke. The aims of our study were to assess
      the risk of stroke after the onset of HZ and to investigate the roles of stroke
      subtype, HZ location and the time interval between HZ onset and stroke. METHODS:
      A self-controlled case-series study was performed on a cohort of patients with
      incident stroke recorded in the German Pharmacoepidemiological Research Database
      (GePaRD), which covers about 20 million persons throughout Germany. We estimated
      adjusted incidence rate ratios (IRR) by comparing the rate of stroke in risk
      periods (i.e., periods following HZ) with the rate of stroke in control periods
      (i.e., periods without HZ) in the same individuals, controlling for both time
      invariant and major potentially time-variant confounders. RESULTS: The cohort
      included 124,462 stroke patients, of whom 6,035 (5%) had at least one HZ
      diagnosis identified in GePaRD either as main hospital discharge diagnosis or as
      HZ treated with antivirals. The risk of stroke was about 1.3 times higher in the
      risk periods 3 months after HZ onset, than in the control periods (IRR: 1.29; 95%
      confidence interval: 1.16-1.44). An elevated risk of similar magnitude was
      observed for ischemic and unspecified stroke, but a 1.5-fold higher risk was
      observed for hemorrhagic stroke. A slightly stronger effect on the risk of stroke
      was also observed during the 3 months after HZ ophthalmicus (HZO) onset (1.59;
      1.10-2.32). The risk was highest 3 and 4 weeks after HZ onset and decreased
      thereafter. CONCLUSIONS: Our study corroborates an increased risk of stroke after
      HZ, which is highest 3 to 4 weeks after HZ onset. The results suggest that the
      risk is more pronounced after HZO and is numerically higher for hemorrhagic than
      for ischemic stroke.

PMID- 27880852
TI  - Clinical Characteristics and Outcomes of Patients with High Ankle-Brachial Index
      from the IMPACT-ABI Study.
AB  - BACKGROUND: Reduced ankle-brachial index (ABI) is a predictor of cardiovascular
      events. However, the significance of high ABI remains poorly understood. This
      study aimed to assess the characteristics and outcomes of patients with high ABI.
      METHODS: The IMPACT-ABI study was a retrospective cohort study that enrolled and
      examined ABI in 3,131 patients hospitalized for cardiovascular disease between
      January 2005 and December 2012. From this cohort, 2,419 patients were identified
      and stratified into two groups: high ABI (> 1.4; 2.6%) and normal ABI (1.0-1.4;
      97.3%). The primary endpoint was the cumulative incidence of major adverse
      cardiovascular events (MACE), including cardiovascular-associated death,
      myocardial infarction, and stroke. RESULTS: Compared with the normal ABI group,
      patients in the high ABI group showed significantly lower body mass index (BMI)
      and hemoglobin level, but had higher incidence of chronic kidney disease and
      hemodialysis. Multivariate logistic regression analysis revealed that
      hemodialysis was the strongest predictor of high ABI (odds ratio, 6.18; 95%
      confidence interval (CI), 3.05-12.52; P < 0.001). During the follow-up (median,
      4.7 years), 172 cases of MACE occurred. Cumulative MACE incidence in patients
      with high ABI was significantly increased compared to that in those with normal
      ABI (32.5% vs. 14.5%; P = 0.005). In traditional cardiovascular risk factors
      adjusted multivariate Cox proportional hazard analysis, high ABI was an
      independent predictor of MACE (hazard ratio, 2.07; 95% CI, 1.02-4.20; P = 0.044).
      CONCLUSION: Lower BMI, chronic kidney disease, and hemodialysis are more frequent
      in patients with high ABI. Hemodialysis is the strongest predictor of high ABI.
      High ABI is a parameter that independently predicts MACE.

PMID- 27880855
TI  - The paradoxical pro- and antiangiogenic actions of resveratrol: therapeutic
      applications in cancer and diabetes.
AB  - Resveratrol, a polyphenol found in grapes, peanuts, and red wine, plays different
      roles in diseases such as cancer and diabetes. Existing information indicates
      that resveratrol provides cardioprotection, as evidenced by superior postischemic
      ventricular recovery, reduced myocardial infarct size, and decreased number of
      apoptotic cardiomyocytes associated with resveratrol treatment in animal models.
      Cardiovascular benefits are experienced in humans with routine but not acute
      consumption of red wine. In this concise review, the paradoxical pro- and
      antiangiogenic effects of resveratrol are described, and different roles for
      resveratrol in the formation of new blood vessels are explained through different
      mechanisms. It is hypothesized that the effects of resveratrol on different cell
      types are not only dependent on its concentration but also on the physical and
      chemical conditions surrounding cells. The findings discussed herein shed light
      on potential therapeutic proapoptotic and antiangiogenic applications of low-dose
      resveratrol treatment in the prevention and treatment of different diseases.

PMID- 27880856
TI  - Direct Analysis in Real-time Mass Spectrometry for Rapid Identification of
      Traditional Chinese Medicines with Coumarins as Primary Characteristics.
AB  - INTRODUCTION: The increasing popularity of traditional Chinese medicines (TCMs)
      necessitates rapid and reliable methods for controlling their quality. Direct
      analysis in real-time mass spectrometry (DART-MS) represents a novel approach to
      analysing TCMs. OBJECTIVE: To develop a quick and reliable method of identifying
      TCMs with coumarins as primary characteristics. METHODOLOGY: DART-MS coupled with
      ion trap mass spectrometry was employed to rapidly identify TCMs with coumarins
      as primary characteristics and to explore the ionisation mechanisms of simple
      coumarins, furocoumarins and pyranocoumarins in detail. With minimal sample
      pretreatment, mass spectra of Fraxini Cortex, Angelicae Pubescentis Radix,
      Peucedani Radix and Psoraleae Fructus samples were obtained within seconds. The
      operating parameters of the DART ion source (e.g. grid electrode voltage and
      ionisation gas temperature) were carefully investigated to obtain high-quality
      mass spectra. The mass spectra of samples and DART-MS/MS spectra of marker
      compounds were used to identify sample materials. RESULTS: Successful
      authentication was achieved by analysing the same materials of different origins.
      Some simple coumarins, furocoumarins and pyranocoumarins can be directly detected
      by DART-MS as marker compounds. CONCLUSION: Our results demonstrated that DART-MS
      can provide a rapid and reliable method for the identification of TCMs containing
      different configurations of coumarins; the method may also be applicable to other
      plants. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27880854
TI  - Increased Paternal Age at Conception Is Associated with Transcriptomic Changes
      Involved in Mitochondrial Function in Elderly Individuals.
AB  - The increased paternal age at conception (PAC) has been associated with autism
      spectrum disorder (ASD), schizophrenia and other neurodevelopmental disorders,
      thus raising questions that imply, potential health concerns in the offspring. As
      opposed to female oogonia, the male germ cells undergo hundreds of cell divisions
      during the fertile years. Thus, the advanced paternal age is associated with
      increase of point mutations in the male spermatogonia DNA, implying that this
      could be the major driving mechanism behind the paternal age effect observed in
      the offspring. In addition to replication errors, DNA replication fidelity and
      inefficient DNA repair machinery in the spermatogonia also contribute to the
      mutagenic load. Our study population consisted of 38 nonagenarians, participants
      in the Vitality 90+ Study, born in the year 1920 (women n = 25, men n = 13), for
      whom the parental birth dates were available. The gene expression profile of the
      study subjects was determined with HumanHT-12 v4 Expression BeadChip from
      peripheral blood mononuclear cells. We used Spearman's rank correlation to look
      for the associations of gene expression with paternal age at conception.
      Associated transcripts were further analyzed with GOrilla and IPA to determine
      enriched cellular processes and pathways. PAC was associated with the expression
      levels of 648 transcripts in nonagenarian subjects. These transcripts belonged to
      the process of mitochondrial translational termination and the canonical pathway
      of Mitochondrial dysfunction, more specifically of Oxidative phosphorylation. The
      observed systematic down-regulation of several mitochondrial respiratory chain
      components implies compromised function in oxidative phosphorylation and thus in
      the production of chemical energy.

PMID- 27880857
TI  - Conformational Flexibility of Limonene Oxide Studied By Microwave Spectroscopy.
AB  - Monoterpenoids are biogenic volatile organic compounds that play a major role in
      atmospheric chemistry by participating in the formation of aerosols. In this
      work, the monoterpenoid (R)-(+)-limonene oxide (C10 H16 O) was characterized in
      the gas phase by Fourier-transform microwave spectroscopy in a supersonic jet.
      Five conformers of limonene oxide, four equatorial and one axial considering the
      configuration of the isopropenyl group, were unambiguously identified from
      analysis of the rotational spectrum. The observed conformers include cis and
      trans forms, which are stabilized by a subtle balance of hydrogen bonds,
      dispersive interactions, and steric effects. Estimated conformational relative
      abundances surprisingly reveal that the abundance of the axial conformer is
      similar to that of some of the equatorial conformers. In addition, the potential
      energy surface was extensively explored by using density functional theory and ab
      initio methods.

PMID- 27880859
TI  - Clinical Education (2016/048).

PMID- 27880858
TI  - Precepting 101: Teaching Strategies and Tips for Success for Preceptors.
AB  - The current shortage of certified nurse-midwives and certified midwives willing
      to serve as preceptors for midwifery education programs limits the number of
      students accepted into education programs. Preceptors are an essential link
      between academic programs and clinical practice and are indispensable to the
      growth of the midwifery profession. Preceptors create a safe environment for
      learning and teach adult learners through a variety of clinical teaching
      strategies. Novice preceptors need training and support to learn a new role, and
      experienced preceptors desire continued support and training. Before starting,
      preceptors need to identify sources of support and mentoring as well as
      understand the academic program's expectations for the student. This article
      draws on the clinical education literature to describe approaches to teaching all
      types of students. Practical strategies for integrating all levels of students
      into busy clinical settings are identified. Two approaches for clinical teaching,
      the Five Minute Preceptor and SNAPPS, are discussed in detail. Strategies for
      providing effective feedback and approaches to student evaluation are provided.

PMID- 27880860
TI  - Precepting Challenge: Helping the Student Attain the Affective Skills of a Good
      Midwife.
AB  - Preparing students for a career in midwifery is a rewarding venture. The
      knowledge and techniques necessary to meet the requirements of a safe, beginning
      level practitioner are familiar to experienced midwives. It is common for
      students to achieve learning outcomes in the classroom (actual or virtual) but
      struggle in the clinical setting. Other students may struggle academically but
      perform smoothly and comfortably when they apply knowledge and skills in the
      clinical setting. The cognitive and psychomotor domains of learning are
      represented by a student's application of knowledge and performance of skills.
      Affective skills of caring and professionalism are equally important. Research
      that describes characteristics of what is considered a good midwife identifies
      affective characteristics associated with effective midwifery practice. By
      attending equally to all domains of learning, the preceptor can more effectively
      support the student in attainment of the skills, values, and beliefs that make a
      good midwife. This article focuses on the acquisition of affective skills by
      students in the clinical setting. When affective skills are well developed, they
      require little attention, but if they are not, the recognition and remediation
      can be a difficult task for the preceptor. Acquisition of affective skills in the
      realms of caring and professionalism are necessary for midwifery practice.
      Effective teaching techniques and knowledge of the affective domain enhance the
      preceptors' ability to evaluate and remediate deficiencies.

PMID- 27880861
TI  - Midwifing the Student: Creating an Effective Learning Environment.

PMID- 27880862
TI  - The Importance of Preceptors: Midwifing the Next Generation.

PMID- 27880863
TI  - Collaborative and Bidirectional Feedback Between Students and Clinical
      Preceptors: Promoting Effective Communication Skills on Health Care Teams.
AB  - Current literature on feedback suggests that clinical preceptors lead feedback
      conversations that are primarily unidirectional, from preceptor to student. While
      this approach may promote clinical competency, it does not actively develop
      students' competency in facilitating feedback discussions and providing feedback
      across power differentials (ie, from student to preceptor). This latter
      competency warrants particular attention given its fundamental role in effective
      health care team communication and its related influence on patient safety.
      Reframing the feedback process as collaborative and bidirectional, where both
      preceptors and students provide and receive feedback, maximizes opportunities for
      role modeling and skills practice in the context of a supportive relationship,
      thereby enhancing team preparedness. We describe an initiative to introduce these
      fundamental skills of collaborative, bidirectional feedback in the nurse
      midwifery education program at the University of California, San Francisco.

PMID- 27880865
TI  - Identifying and Addressing Problems for Student Progression in Midwifery Clinical
      Education.
AB  - Identifying challenges to progression for a health care profession student who is
      not meeting expectations in a busy clinical practice can be challenging yet can
      lead to assisting the student toward success. Preceptor preparation includes
      acquiring knowledge about the student's education program, understanding federal
      regulations designed to protect students, gathering background information about
      a student, learning to provide feedback, structuring the clinical experience, and
      completing student evaluations. Students in health care professions may have
      difficulties with cognitive, affective, or psychomotor learning, and the clinical
      preceptor can identify problems for student progression within these learning
      domains. Subsequently, specific solutions that are tailored to the individual
      student's needs can be developed, implemented, and evaluated. A structured
      evaluation of the student's performance by the clinical preceptor, in accordance
      with the education program's parameters, is essential. Through a structured
      process, preceptors can assist many students to achieve success, in spite of
      challenges. This article describes how the preceptor can prepare, identify the
      type(s) of problem(s), and develop learning solutions for students who are
      experiencing difficulties in clinical settings.

PMID- 27880867
TI  - Psittacine cognition: Individual differences and sources of variation.
AB  - Both the number and breadth of avian cognition studies have expanded in the past
      three decades. Parrots have a long history as subjects in avian cognition
      research. This paper summarizes results from a number of parrot species tested on
      basic learning, and physical & social cognitive processes, with an emphasis on
      individual differences. Early psittacine studies were aimed at demonstrating a
      particular cognitive ability existed in a given species. Because of this proof of
      capacity focus, early studies typically included only a single individual or a
      dyad of parrots. Existing reviews of parrot cognition tend to focus on a
      particular cognitive component in a single species, or even a single individual.
      Despite the narrow focus, results from increasing sample sizes show intraspecific
      variation across a variety of cognitive assessments and parrot species.
      Intraspecific variability in performance on cognitive tasks highlights the need
      for establishing a cognitive normal range for a given species and process. To
      accomplish this, large numbers of individuals need to be tested and non-cognitive
      sources of variability need to be controlled. Once species typical cognitive
      normal ranges are established, cognitive comparisons can be made between parrot
      species and between parrots and other taxa.

PMID- 27880866
TI  - TGF-beta1 stimulates movement of renal proximal tubular epithelial cells in a
      three-dimensional cell culture via an autocrine TGF-beta2 production.
AB  - TGF-betas are multifunctional cytokines, but their roles in human renal
      homeostasis are not fully understood. This study investigated the role of TGF
      beta1 in the movement of human renal proximal tubular epithelial cells (PTECs) in
      a three-dimensional (3D) model. HKC-8 cells, a human PTEC line, were grown in a
      3D collagen culture system. Cell movement was observed under a microscope. The
      gene expression was examined using PCR Arrays or qRT-PCR, and protein levels by
      Western blot. Here, we showed that the tight junction structure formed between
      adjacent cells of a HKC-8 cell colony in 3D cultures, and TGF-beta1 stimulated
      their movement, evidenced by the appearance of fingerlike pseudopodia in the
      leader cells at the edge of the colonies. The cell movement of these human PTECs
      was correlated with up-regulation of both MMP2 and MMP9 and down-regulation or
      inactivation of PLAUR and PTK2B. Analysis of TGF-beta signaling targets confirmed
      autocrine production of TGF-beta2 and its cleaving enzyme furin as well as SNAI1
      by TGF-beta1stimulation. Knockdown of TGF-beta2 expression disrupted TGF-beta1
      stimulated PTEC invasiveness, which was correlated with the down-regulation of
      MMP2 and MMP9. In conclusion, the activation of TGF-beta receptor autocrine
      signaling by up-regulated TGF-beta2 may play a pivotal role in TGF-beta1-induced
      human PTEC movement, which could be mediated at least by both MMP2 and MMP9.

PMID- 27880868
TI  - Origin and evolution of the metazoan non-coding regulatory genome.
AB  - Animals rely on genomic regulatory systems to direct the dynamic spatiotemporal
      and cell-type specific gene expression that is essential for the development and
      maintenance of a multicellular lifestyle. Although it is widely appreciated that
      these systems ultimately evolved from genomic regulatory mechanisms present in
      single-celled stem metazoans, it remains unclear how this occurred. Here, we
      focus on the contribution of the non-coding portion of the genome to the
      evolution of animal gene regulation, specifically on recent insights from non
      bilaterian metazoan lineages, and unicellular and colonial holozoan sister taxa.
      High-throughput next-generation sequencing, largely in bilaterian model species,
      has led to the discovery of tens of thousands of non-coding RNA genes (ncRNAs),
      including short, long and circular forms, and uncovered the central roles they
      play in development. Based on the analysis of non-bilaterian metazoan,
      unicellular holozoan and fungal genomes, the evolution of some ncRNAs, such as
      Piwi-interacting RNAs, correlates with the emergence of metazoan
      multicellularity, while others, including microRNAs, long non-coding RNAs and
      circular RNAs, appear to be more ancient. Analysis of non-coding regulatory DNA
      and histone post-translational modifications have revealed that some cis
      regulatory mechanisms, such as those associated with proximal promoters, are
      present in non-animal holozoans, while others appear to be metazoan innovations,
      most notably distal enhancers. In contrast, the cohesin-CTCF system for
      regulating higher-order chromatin structure and enhancer-promoter long-range
      interactions appears to be restricted to bilaterians. Taken together, most
      bilaterian non-coding regulatory mechanisms appear to have originated before the
      divergence of crown metazoans. However, differential expansion of non-coding RNA
      and cis-regulatory DNA repertoires in bilaterians may account for their increased
      regulatory and morphological complexity relative to non-bilaterians.

PMID- 27880872
TI  - Manganese showcase symposium.

PMID- 27880871
TI  - Spray-dried nanocrystals for a highly hydrophobic drug: Increased drug loading,
      enhanced redispersity, and improved oral bioavailability.
AB  - For a highly hydrophobic and drug, it is difficult to formulate and solidify its
      nanocrystals with high drug loading and good redispersity. In this study,
      Allisartan Isoproxil was used as a model drug, and SDS was tested in combination
      with sugar alcohols to improve the drug loading and redispersity for its spray
      dried nanocrystals, simultaneously. These spray-dried nanocrystals had high drug
      loading of 61.7% and good redispersity, which was mainly attributed to the
      addition of SDS. In addition, the nanocrystals were characterized by scanning
      electron microscopy, differential scanning calorimetry, X-ray power diffraction
      analysis, Fourier transform infrared spectroscopy and Raman spectroscopy. The
      results showed that Allisartan Isoproxil was unchanged in chemical structure, but
      was partially amorphous. Regarding the in vitro dissolution, the optimism
      formulation shown an increased dissolution compared with the bulk drug and
      aggregated nanocrystals. Importantly, the optimum formulation increased the oral
      bioavailability of crude ALS-3 for 4.73 times. In conclusion, we developed a
      method to solidify aqueous nanocrystals with increased drug loading, good
      redispersity and improved bioavailability for high hydrophobic drugs.

PMID- 27880873
TI  - Nurses' smoking habits and their professional smoking cessation practices. A
      systematic review and meta-analysis.
AB  - BACKGROUND: A better understanding of whether nurses' own smoking behaviours
      influence their engagement with smoking cessation interventions is needed. AIM:
      To establish whether the smoking status of nurses is associated with their
      professional smoking cessation practices. METHODS: Twelve electronic databases
      covering English and Spanish language publications from 01 Jan, 1996 to 25 Mar,
      2015 were systematically searched. Studies were included if they reported nurses'
      smoking cessation practices in relation to their personal smoking habits.
      Proportions of nurses' smoking status and smoking cessation practices were pooled
      across studies using random effects meta-analysis. RESULTS: Fifteen studies were
      included in this systematic review. Levels of reportedsmoking cessation
      interventions were generally low across the studies. The meta-analyses suggested
      that nurses' personal smoking status was not associated significantly with nurses
      always asking patients about their smoking, but nurses who smoked were 13% less
      likely to advise their patients to quit and 25% less likely to arrange smoking
      cessation follow-up. More intense interventions (assessing motivation and
      assisting) were not significantly associated with the smoking status of the
      nurse. CONCLUSIONS: The smoking status of nurses appears to have a negative
      impact in the delivery of smoking cessation practices. The overall level of
      nurses' engagement with the delivery of smoking cessation interventions requires
      attention if nurses are to be effective agents of smoking cessation.

PMID- 27880869
TI  - The impact of metagenomic interplay on the mosquito redox homeostasis.
AB  - Mosquitoes are exposed to oxidative challenges throughout their life cycle. The
      primary challenge comes from a blood meal. The blood digestion turns the midgut
      into an oxidative environment, which imposes pressure not only on mosquito
      fecundity and other physiological traits but also on the microbiota in the
      midgut. During evolution, mosquitoes have developed numerous oxidative defense
      mechanisms to maintain redox homeostasis in the midgut. In addition to
      antioxidants, SOD, catalase, and glutathione system, sufficient supply of the
      reducing agent, NADPH, is vital for a successful defense against oxidative
      stress. Increasing evidence indicates that in response to oxidative stress, cells
      reconfigure metabolic pathways to increase the generation of NADPH through NADP
      reducing networks including the pentose phosphate pathway and others. The
      microbial homeostasis is critical for the functional contributions to various
      host phenotypes. The symbiotic microbiota is regulated largely by the Duox-ROS
      pathway in Drosophila. In mosquitoes, Duox-ROS pathway, heme-mediated signaling,
      antimicrobial peptide production and C-type lectins work in concert to maintain
      the dynamic microbial community in the midgut. Microbial mechanisms against
      oxidative stress in this context are not well understood. Emerging evidence that
      microbial metabolites trigger host oxidative response warrants further study on
      the metagenomic interplay in an oxidative environment like mosquito gut
      ecosystem. Besides the classical Drosophila model, hematophagous insects like
      mosquitoes provide an alternative model system to study redox homeostasis in a
      symbiotic metagenomic context.

PMID- 27880874
TI  - Specialized hybrid learners resolve Rogers' paradox about the adaptive value of
      social learning.
AB  - Culture is considered an evolutionary adaptation that enhances reproductive
      fitness. A common explanation is that social learning, the learning mechanism
      underlying cultural transmission, enhances mean fitness by avoiding the costs of
      individual learning. This explanation was famously contradicted by Rogers (1988),
      who used a simple mathematical model to show that cheap social learning can
      invade a population without raising its mean fitness. He concluded that some
      crucial factor remained unaccounted for, which would reverse this surprising
      result. Here we extend this model to include a more complex environment and
      limited resources, where individuals cannot reliably learn everything about the
      environment on their own. Under such conditions, cheap social learning evolves
      and enhances mean fitness, via hybrid learners capable of specializing their
      individual learning. We then show that while spatial or social constraints hinder
      the evolution of hybrid learners, a novel social learning strategy, complementary
      copying, can mitigate these effects.

PMID- 27880875
TI  - Stable polymorphism of cooperators and punishers in a public goods game.
AB  - The role of punishment in the maintenance of cooperation has been emphasized
      recently. However, the maintenance of punishment is not an obvious consequence
      because punishment itself is also a public good; it is costly to perform and
      hence vulnerable to exploitation. For example, cooperative punishers, who help
      others and punish free riders, are disadvantageous in competition against pure
      cooperators, who cooperate but do not punish free riders. In addition, pure
      punishers, who do not help others but punish free riders, have been considered to
      be selfish in conventional models, because they do not perform cooperation.
      Instead, here we assume that performing either cooperation or punishment is
      sufficient to avoid accusation from others because not only cooperators but also
      pure punishers contribute to their society by reducing a threat of free riders.
      Under such an assumption, we analyzed the evolutionary dynamics of pure
      cooperators, pure punishers and free riders. We first showed that cooperation is
      never maintained in a well-mixed population. When the population is spatially
      structured, however, oscillatory rock-paper-scissors dynamics among those
      strategies appear. We further find that a stable polymorphism of the three
      strategies is attained when mutation is introduced. Our results indicate that
      cooperation and punishment can be stably maintained even when one cannot perform
      cooperation and punishment at the same time, and provide insights about the
      coexistence of cooperation and punishment in real societies.

PMID- 27880876
TI  - An integrative review of methylation at the serotonin transporter gene and its
      dialogue with environmental risk factors, psychopathology and 5-HTTLPR.
AB  - Gene-environment (G*E) interactions have largely been regarded as the root of
      many complex disorders, including several psychiatric disorders. In this regard,
      it has been hypothesized that epigenetic mechanisms may be the main mediators of
      such interactions. Of particular interest is the previously described interaction
      between psychosocial stress and genetic variability of the serotonin transporter
      gene (SLC6A4) in its polymorphic region 5-HTTLPR. Here we review the literature
      concerning SLC6A4 methylation in association with environmental, clinical or
      genetic variables. While SLC6A4 hypermethylation has typically been described to
      be independently associated with both early life stress and depressive disorders,
      only a few papers address whether methylation could mediate the interaction
      between stress and 5-HTTLPR in predicting psychopathological risk. Nevertheless,
      research preliminarily indicates a methylation-driven increased vulnerability of
      carriers of the short allele of 5-HTTLPR to psychiatric disorders when exposed to
      early stress or soon after exposure to stress.

PMID- 27880877
TI  - Association of the occurrence of Brazilian spotted fever and Atlantic rain forest
      fragmentation in the Sao Paulo metropolitan region, Brazil.
AB  - Brazilian Spotted Fever (BSF) is a zoonotic disease caused by the bacterium
      Rickettsia rickettsii. In the Sao Paulo Metropolitan Region (SPMR) it is
      transmitted by Amblyomma aureolatum ticks. In this region, annual lethality of
      the disease can reach 80% and spatial occurrence depends on environmental factors
      and more particularly on the presence and interaction of domestic and wild
      carnivores as well as the presence and characteristics of the remnant Atlantic
      Rain Forest patches. This study analyzed the association between forest
      fragmentation and its influence on the risk of occurrence of the disease in the
      human population. Domestic dogs tested for R. rickettsii antibodies in nine
      different areas under the influence of different patterns of Rain Forest
      fragmented landscapes and human occupancy. Landscape metrics were obtained by
      analyzing satellite images and high-resolution orthophotos. Principal component
      analysis (PCA) was used to determine among the different landscape variables the
      one that could best explain the data variance, and the results were tested
      against canine seroprevalence in order to address disease occurrence risk levels.
      From 270 canine samples, the seroprevalence ranged from 0 to 37%. PCA showed an
      inverse correlation between functionally connected large forest patches and the
      canine seroprevalence for R. rickettsii (p=0.030; Spearman's R=-0.683), while
      there was a positive correlation between forest border effect and canine
      seroprevalence (p=0.037; Spearman's R=- 0.909). The further attributed disease
      occurrence risk level supported the real spatial prevalence of the disease
      reported for the last eight years (p=0.023; Spearman's R=0.63). The results
      suggest an important relation of deforestation and fragmentation with the
      occurrence of BSF in the SPMR.

PMID- 27880878
TI  - Neurocysticercosis infection and disease-A review.
AB  - Neurocysticercosis (NCC) is the most common parasitic disease of the human
      central nervous system (CNS), a pleomorphic disease with a diverse array of
      clinical manifestations. The infection is pleomorphic and dependent on a complex
      range of interconnecting factors, including number and size of the cysticerci,
      their stage of development and localisation within the brain with resulting
      difficulties in accurate diagnosis and staging of the disease. This review
      examines the factors that contribute to the accurate assessment of NCC
      distribution and transmission that are critical to achieving robust disease
      burden calculations. Control and prevention of T. solium transmission should be a
      key priority in global health as intervention can reduce the substantial
      healthcare and economic burdens inflicted by both NCC and taeniasis. Surveillance
      systems need to be better established, including implementing obligatory
      notification of cases. In the absence of reliable estimates of its global burden,
      NCC will remain-along with other endemic zoonoses, of low priority in the eyes of
      funding agencies-a truly neglected disease.

PMID- 27880870
TI  - Formation and processing of DNA damage substrates for the hNEIL enzymes.
AB  - Reactive oxygen species (ROS) are harnessed by the cell for signaling at the same
      time as being detrimental to cellular components such as DNA. The genome and
      transcriptome contain instructions that can alter cellular processes when
      oxidized. The guanine (G) heterocycle in the nucleotide pool, DNA, or RNA is the
      base most prone to oxidation. The oxidatively-derived products of G consistently
      observed in high yields from hydroxyl radical, carbonate radical, or singlet
      oxygen oxidations under conditions modeling the cellular reducing environment are
      discussed. The major G base oxidation products are 8-oxo-7,8-dihydroguanine (OG),
      5-carboxamido-5-formamido-2-iminohydantoin (2Ih), spiroiminodihydantoin (Sp), and
      5-guanidinohydantoin (Gh). The yields of these products show dependency on the
      oxidant and the reaction context that includes nucleoside, single-stranded DNA
      (ssDNA), double-stranded DNA (dsDNA), and G-quadruplex DNA (G4-DNA) structures.
      Upon formation of these products in cells, they are recognized by the DNA
      glycosylases in the base excision repair (BER) pathway. This review focuses on
      initiation of BER by the mammalian Nei-like1-3 (NEIL1-3) glycosylases for removal
      of 2Ih, Sp, and Gh. The unique ability of the human NEILs to initiate removal of
      the hydantoins in ssDNA, bulge-DNA, bubble-DNA, dsDNA, and G4-DNA is outlined.
      Additionally, when Gh exists in a G4 DNA found in a gene promoter, NEIL-mediated
      repair is modulated by the plasticity of the G4-DNA structure provided by
      additional G-runs flanking the sequence. On the basis of these observations and
      cellular studies from the literature, the interplay between DNA oxidation and BER
      to alter gene expression is discussed.

PMID- 27880879
TI  - Arsenic levels among pregnant women and newborns in Canada: Results from the
      Maternal-Infant Research on Environmental Chemicals (MIREC) cohort.
AB  - Arsenic is a common environmental contaminant from both naturally-occurring and
      anthropomorphic sources and human exposure can be detected in various tissues.
      Its toxicity depends on many factors including the chemical form, valence state,
      bioavailability, metabolism and detoxification within the human body. Of
      paramount concern, particularly with respect to health effects in children, is
      the timing of exposure as the prenatal and early life periods are more
      susceptible to toxic effects. The Maternal-Infant Research on Environmental
      Chemicals (MIREC) cohort was established to obtain national-level biomonitoring
      data for approximately 2,000 pregnant women and their infants between 2008 and
      2011 from 10 Canadian cities. We measured total arsenic (As) in 1st and 3rd
      trimester maternal blood, umbilical cord blood, and infant meconium and speciated
      arsenic in 1st trimester maternal urine. Most pregnant women had detectable
      levels of total arsenic in blood (92.5% and 87.3%, respectively, for 1st and 3rd
      trimester); median difference between 1st and 3rd trimester was 0.1124ug/L
      (p<0.0001), but paired samples were moderately correlated (Spearman r=0.41,
      p<0.0001). Most samples were below the LOD for umbilical cord blood (50.9%) and
      meconium (93.9%). In 1st trimester urine samples, a high percentage (>50%) of
      arsenic species (arsenous acid (As-III), arsenic acid (As-V), monomethylarsonic
      acid (MMA), and arsenobetaine (AsB)) were also below the limit of detection,
      except dimethylarsinic acid (DMA). DMA (>85% detected) ranged from <LOD to 64.42
      (95th percentile: 11.99)ugAs/L. There was a weak but significant correlation
      between total arsenic in blood and specific gravity-adjusted DMA in urine
      (Spearman r=0.33, p<0.0001). Among this population of pregnant woman and
      newborns, levels of arsenic measured in blood and urine were lower than national
      population figures for Canadian women of reproductive age (20-39 years). In
      general, higher arsenic levels were observed in women who were older, foreign
      born (predominantly from Asian countries), and had higher education. Further
      research is needed to elucidate sources of exposure and factors that may
      influence arsenic exposure in pregnant women and children.

PMID- 27880880
TI  - Heartfelt embodiment: Changes in body-ownership and self-identification produce
      distinct changes in interoceptive accuracy.
AB  - Interoceptive and exteroceptive information are both essential for the
      construction and update of self-awareness. Whereas several studies have shown how
      interoceptive accuracy or cardiac feedback influences body-awareness, no studies
      have looked at the reverse effect, namely how exteroceptively-driven changes in
      body-ownership and self-identification can influence individuals' ability to
      detect internal bodily signals. We exposed participants to the Rubber Hand
      Illusion (Experiment 1) and to the Enfacement Illusion (Experiment 2), and tested
      how this change in the sense of body-ownership and self-identification affected
      their interoceptive accuracy (IAcc). The heartbeat-counting task was used to
      measure IAcc before the bodily illusions, and then the same task was interleaved
      with periods of visuo-tactile stimulation, during which synchronous and
      asynchronous multisensory stimulation was applied. We found that a change in body
      ownership significantly improved performance of participants with lower
      interoceptive accuracy. In contrast, a change in self-identification
      significantly decreased performance of participants with higher interoceptive
      accuracy. These results suggest that changes in different domains of self
      awareness can differentially impact individuals' ability to accurately detect
      signals arising from within the body, highlighting the distinct role that
      interoceptive signals play for different facets of bodily self-consciousness.

PMID- 27880881
TI  - Learning language from within: Children use semantic generalizations to infer
      word meanings.
AB  - One reason that word learning presents a challenge for children is because
      pairings between word forms and meanings are arbitrary conventions that children
      must learn via observation - e.g., the fact that "shovel" labels shovels. The
      present studies explore cases in which children might bypass observational
      learning and spontaneously infer new word meanings: By exploiting the fact that
      many words are flexible and systematically encode multiple, related meanings. For
      example, words like shovel and hammer are nouns for instruments, and verbs for
      activities involving those instruments. The present studies explored whether 3-
      to 5-year-old children possess semantic generalizations about lexical
      flexibility, and can use these generalizations to infer new word meanings: Upon
      learning that dax labels an activity involving an instrument, do children
      spontaneously infer that dax can also label the instrument itself? Across four
      studies, we show that at least by age four, children spontaneously generalize
      instrument-activity flexibility to new words. Together, our findings point to a
      powerful way in which children may build their vocabulary, by leveraging the fact
      that words are linked to multiple meanings in systematic ways.

PMID- 27880882
TI  - The regularity game: Investigating linguistic rule dynamics in a population of
      interacting agents.
AB  - Rules are an efficient feature of natural languages which allow speakers to use a
      finite set of instructions to generate a virtually infinite set of utterances.
      Yet, for many regular rules, there are irregular exceptions. There has been
      lively debate in cognitive science about how individual learners acquire rules
      and exceptions; for example, how they learn the past tense of preach is preached,
      but for teach it is taught. However, for most population or language-level models
      of language structure, particularly from the perspective of language evolution,
      the goal has generally been to examine how languages evolve stable structure, and
      neglects the fact that in many cases, languages exhibit exceptions to structural
      rules. We examine the dynamics of regularity and irregularity across a population
      of interacting agents to investigate how, for example, the irregular teach
      coexists beside the regular preach in a dynamic language system. Models show that
      in the absence of individual biases towards either regularity or irregularity,
      the outcome of a system is determined entirely by the initial condition. On the
      other hand, in the presence of individual biases, rule systems exhibit frequency
      dependent patterns in regularity reminiscent of patterns found in natural
      language. We implement individual biases towards regularity in two ways: through
      'child' agents who have a preference to generalise using the regular form, and
      through a memory constraint wherein an agent can only remember an irregular form
      for a finite time period. We provide theoretical arguments for the prediction of
      a critical frequency below which irregularity cannot persist in terms of the
      duration of the finite time period which constrains agent memory. Further, within
      our framework we also find stable irregularity, arguably a feature of most
      natural languages not accounted for in many other cultural models of language
      structure.

PMID- 27880883
TI  - Anti-proliferative and anti-inflammatory effects of 3beta,6beta,16beta
      Trihydroxylup-20(29)-ene on cutaneous inflammation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: 3beta,6beta,16beta-Trihydroxylup-20(29)-ene
      (TTHL) is a triterpene isolated from the flowers of Combretum leprosum, a plant
      used in folk medicine in the north of Brazil for the treatment of skin disorders.
      AIM OF THE STUDY: In the present study, TTHL was evaluated as a potential topical
      anti-inflammatory and anti-proliferative agent through in vivo and in vitro
      models. MATERIAL AND METHODS: Anti-inflammmatory and anti-proliferative effects
      of TTHL were assessed using Swiss mice in acute and chronic models of skin
      inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA) application. Anti
      proliferative activity was proved through in vitro experiments with the HaCaT
      human keratinocyte cell line. RESULTS: Treatment with TTHL inhibited inflammatory
      parameters such as oedema formation and cellular infiltration in acute and
      chronic models. In the chronic model, TTHL also inhibited epidermal
      hyperproliferation, as evidenced by reduction of epidermis thickness and
      proliferating cell nuclear antigen expression. The anti-proliferative effect was
      confirmed by the capability of TTHL in reducing the proliferation and inducing
      cell apoptosis of HaCaT cells. Suggesting a mechanism of action, TTHL showed
      activation of corticosteroid receptors, but without the induction of
      corticosteroid-related cutaneous side effects. CONCLUSION: Our results
      demonstrate consistent anti-inflammatory and anti-proliferative activity and
      assign TTHL as a valuable tool in the development of a new treatment for skin
      inflammatory and proliferative diseases, such as psoriasis.

PMID- 27880886
TI  - Hippocampal and diencephalic pathology in developmental amnesia.
AB  - Developmental amnesia (DA) is a selective episodic memory disorder associated
      with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the
      systemic impact of hypoxia-ischaemia, the resulting brain damage was previously
      reported to be largely limited to the hippocampus. However, the thalamus and the
      mammillary bodies are parts of the hippocampal-diencephalic network and are
      therefore also at risk of injury following hypoxic-ischaemic events. Here, we
      report a neuroimaging investigation of diencephalic damage in a group of 18
      patients with DA (age range 11-35 years), and an equal number of controls.
      Importantly, we uncovered a marked degree of atrophy in the mammillary bodies in
      two thirds of our patients. In addition, as a group, patients had mildly reduced
      thalamic volumes. The size of the anterior-mid thalamic (AMT) segment was
      correlated with patients' visual memory performance. Thus, in addition to the
      hippocampus, the diencephalic structures also appear to play a role in the
      patients' memory deficit.

PMID- 27880888
TI  - Evidence of a different landing strategy in subjects with chronic ankle
      instability.
AB  - The purpose of the study is to evaluate the discriminative validity of the
      multiple hop test (MHT) for chronic ankle instability (CAI). The dynamic postural
      control of 51 CAI subjects and 52 uninjured controls was assessed using the MHT.
      To evaluate dynamic postural control, the type and number of balance errors were
      analysed and the time to complete the MHT was measured. Between-group differences
      of time scores and balance errors, identified as being change-in-support strategy
      errors (CSS) or fixed-support strategy errors (FSS), were assessed. The area
      under curve of the outcomes was determined and likelihood ratios (LRs) were
      calculated based upon their most optimal cut off point. When compared to
      uninjured controls, CAI subjects needed significantly more time to perform the
      test (p<0.001) and made significantly more CSS errors (p<0.001). When 1 positive
      outcome (time score or CSS errors) was considered as a criterion, the LR+ was 2
      and the LR- 0.08. In the case of 2 positive outcomes (time score and CSS errors),
      the LR+ was 7.1 and the LR- 0.49. CAI subjects have an impaired dynamic postural
      control and rely on a different postural strategy to restore balance. The MHT has
      good discriminative validity for CAI.

PMID- 27880884
TI  - Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on
      a high fat and vitamin D3 induced rodent model of atherosclerosis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The Angong Niuhuang Pill (ANP) is a well known
      Chinese traditional therapeutic for the treatment for diseases affecting the
      Central Nervous System (CNS). Components of the ANP formulation, including Bovis
      Calculus Sativus, Pulvis Bubali Comus Concentratus, Moschus, Margarita,
      Cinnabaris, Realgar, Coptidis Rhizoma, Scutellariae Radix, Gardeniae Fructus,
      Curcumae Radix, and Bomeolum Syntheticum, have been used for the treatment of
      stroke, encephalitis and emergency meningitis across Asia, especially in China
      for hundreds of years. OBJECTIVE: The goal of this study was to investigate the
      anti-atherosclerosis and cardio-protective effects of ANP administration using a
      rodent model of atherosclerosis induced by a high fat and vitamin D3. METHODS:
      Specific Pathogen-Free (SPF) 78 male SD rats were randomly divided into a control
      group and 5 atherosclerotic model groups. The atherosclerotic groups were divided
      to receive either Simvastatin (SVTT, 0.005g/kg), Low-dose ANP (0.125g/kg), Medium
      dose ANP (0.25g/kg), and High-dose ANP (0.5g/kg). Following adaptive feeding for
      one week, atherosclerosis was induced and the atherosclerosis model was
      established. Experimental drugs (either simvastatin or ANP) or normal saline were
      administered intragastrically once daily for 9 weeks starting from the 8th week.
      A carotid artery ultrasound was performed at the 17th week to determine whether
      atherosclerosis had been induced. After the atherosclerosis model was
      successfully established, platelet aggregation rates, serum biochemical indices,
      apoptosis-related Bcl-2, Bax proteins levels in the heart were assayed.
      Pathological and histological analysis was completed using artery tissue from
      different experimental different groups to assess the effects of ANP. RESULTS:
      ANP significantly decreased aortic membrane thickness, the maximum platelet
      aggregation rates, and the ratio of low density lipoprotein cholesterol (LDL) to
      high density lipoprotein cholesterol (HDL). In addition, ANP significantly
      reduced serum contents of total cholesterol, low density lipoprotein,
      malondialdehyde, troponin I, high-sensitivity C-reactive protein, and lactate
      dehydrogenase. ANP markedly improved abnormal pathological conditions of the
      aorta and heart, and helped to prevent myocardial apoptosis. CONCLUSIONS: We have
      demonstrated that ANP has robust ant-atherosclerosis and cardio-protective
      effects on a high-fat and vitamin D3 - induced rodent model of atherosclerosis
      due to its antiplatelet aggregation, lipid regulatory, antioxidant, anti
      inflammatory and anti-apoptotic properties.

PMID- 27880887
TI  - De novo lead optimization of triazine derivatives identifies potent
      antimalarials.
AB  - Malaria is a life-threatening disease caused by Plasmodium parasites among which
      Plasmodium falciparum is the most deadly. Due to the widespread resistance of the
      current antimalarial drugs, intense research efforts are focused on
      identification of new and potent antimalarials. We report here, a structure based
      drug discovery strategy for design of a series of effective and novel triazine
      based antimalarials. The X-ray structure of P. falciparum methyl transferase
      (PfPMT) is used as a target as it is unique to the parasite. The triazine
      molecules designed and synthesized showed low micro-molar activity against
      malarial parasite cell lines. Molecular dynamics simulations on the PfPMT
      inhibitor complex shed light on the inhibition mechanism for further optimization
      of the lead compounds.

PMID- 27880889
TI  - Milk composition of free-ranging red hartebeest, giraffe, Southern reedbuck and
      warthog and a phylogenetic comparison of the milk of African Artiodactyla.
AB  - The composition of major nutrients and fatty acids of the milk of three species,
      red hartebeest, Southern reedbuck and warthog, and milk fatty acids of giraffe,
      that have not been published before, are reported, and together with the same
      parameters of 11 species previously published, were incorporated in a
      phylogenetic comparison. Unique properties of milk composition have been
      observed. Southern reedbuck milk seems to have a complex casein composition,
      similar to that of sheep. Milk composition varies between species. Although some
      differences may be ascribed to biological condition, such as stage of lactation,
      or ecological factors, such as availability of certain nutrients, the
      contribution by evolutionary history is not well documented and the emphasis is
      usually on the composition of the macro nutrients. Phylogenetic comparisons often
      lack representatives of multiple species of taxonomic groups and sub-groups. To
      date phylogenetic comparisons of milk composition have been carried out by using
      data from different publications. The problem with this approach is that the
      ecological factors cannot be completely ruled out. A statistical phylogenetic
      comparison by PCA between 15 species representing 7 different suborders, families
      or subfamilies of African Artiodactyla was carried out. The phylogenetic
      properties showed that the milk composition of the Bovinae, represented here by
      the subfamilies Bovini and Tragelaphini, differs from the other taxonomic groups,
      in that the Alcelaphinae had a high milk fat content of the medium chain length
      fatty acids C8-C12 (>17% of total fatty acids) and the Hippotraginae high amounts
      of oligosaccharides (>0.4%).

PMID- 27880891
TI  - A novel 3D in vitro metastasis model elucidates differential invasive strategies
      during and after breaching basement membrane.
AB  - Invasive breast cancer and other tumors of epithelial origin must breach a layer
      of basement membrane (BM) that surrounds the primary tumor before invading into
      the adjacent extracellular matrix. To analyze invasive strategies of breast
      cancer cells during BM breaching and subsequent invasion into a collagen I-rich
      extracellular matrix (ECM), we developed a physiologically relevant 3D in vitro
      model that recreates the architecture of a solid tumor with an intact,
      degradable, cell-assembled BM layer embedded in a collagen I environment. Using
      this model we demonstrate that while the BM layer fully prevents dissemination of
      non-malignant cells, cancer cells are capable of breaching it and invading into
      the surrounding collagen, indicating that the developed system recreates a
      hallmark of invasive disease. We demonstrate that cancer cells exhibiting
      individual invasion in collagen matrices preferentially adopt a specific mode of
      collective invasion when transmigrating a cell-assembled BM that is not observed
      in any other tested fibrillar, non-fibrillar, or composite ECM. Matrix-degrading
      enzymes are found to be crucial during BM breaching but not during subsequent
      invasion in the collagen matrix. It is further shown that multicellular
      transmigration of the BM is less susceptible to pharmacological MMP inhibition
      than multicellular invasion in composite collagen/basement membrane extract
      matrices. The newly developed in vitro model of metastasis allows 3D cancer cell
      invasion to be studied not only as a function of a particular tumor's genetics
      but also as a function of its heterogeneous environment and the different stages
      of invasion. As such, this model is a valuable new tool with which to dissect
      basic mechanisms of invasion and metastasis and develop new therapeutic
      approaches in a physiologically relevant, yet inexpensive and highly tunable, in
      vitro setting.

PMID- 27880890
TI  - Potential antidepressant and resilience mechanism revealed by metabolomic study
      on peripheral blood mononuclear cells of stress resilient rats.
AB  - Resilience is an active coping response to stress, which plays a very important
      role in major depressive disorder study. The molecular mechanisms underlying such
      resilience are poorly understood. Peripheral blood mononuclear cells (PBMCs) were
      promising objects in unveiling the underlying pathogenesis of resilience. Hereby
      we carried out successive study on PBMCs metabolomics in resilient rats of
      chronic unpredictable mild stress (CUMS) model. A gas chromatography-mass
      spectrometry (GC-MS) metabolomic approach coupled with principal component
      analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS
      DA) was used to detect differential metabolites in PBMCs of resilient rats.
      Ingenuity Pathways Analysis (IPA) was applied for pathway analysis. A set of
      differential metabolites including Malic acid, Ornithine, l-Lysine, Stigmasterol,
      Oleic acid, gamma-Tocopherol, Adenosine and N-acetyl-d-glucosamine were
      significantly altered in resilient rats, meanwhile promoting antidepressant
      research. As revealed by IPA that aberrant energy metabolism, HIFalpha signaling,
      neurotransmitter, O-GlcNAcylation and cAMP signaling cascade in peripheral might
      be evolved in the pathogenesis of coping mechanism. The GC-MS based metabolomics
      may contribute to better understanding of resilience, as well as shedding light
      on antidepressant discovery.

PMID- 27880892
TI  - Electrospinning versus microfluidic spinning of functional fibers for biomedical
      applications.
AB  - Micro- or nanofiber-based materials have extensive applications in biomedical
      fields due to their capability to mimic many aspects of physiological
      microenvironment in vivo. Fabricating micro- or nanofibers using biocompatible
      and biodegradable materials is becoming of great interest in the area of
      biomaterials and tissue engineering. Among the various technologies,
      electrospinning and microfluidic spinning are the two promising approaches to
      produce fibers at micro- and nano-scale. Choosing an appropriate spinning method
      is critical important for a specific application. Although some review papers on
      each spinning method have been published, a review comparing these two methods
      has not been reported yet. In this review, we present an overview of the two
      spinning methods including the spinning principle, their unique features and
      materials selections. Several applications of fibers spun by both methods,
      especially in tissue engineering, organ function regeneration and drug delivery
      are introduced. The current challenges, future directions and potential
      applications of these approaches are discussed as well.

PMID- 27880893
TI  - Postoperative outcomes and quality of life following hysterectomy by natural
      orifice transluminal endoscopic surgery (NOTES) compared to laparoscopy in women
      with a non-prolapsed uterus and benign gynaecological disease: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To critically appraise studies comparing benefits and harms in women
      with benign disease without prolapse undergoing hysterectomy by natural orifice
      transluminal endoscopic surgery (NOTES) versus laparoscopy. STUDY DESIGN: We
      followed the PRISMA guidelines. We searched MEDLINE, EMBASE and CENTRAL for
      randomised controlled trials (RCTs), controlled clinical trials (CCTs) and cohort
      studies comparing NOTES with laparoscopy assisted vaginal hysterectomy (LAVH) or
      total laparoscopic hysterectomy (TLH) in women bound to undergo removal of a non
      prolapsed uterus for benign disease. Two authors searched and selected studies,
      extracted data and assessed the risk of bias independently. Any disagreement was
      resolved by discussion or arbitration. RESULTS: We did not find RCTs but
      retrieved two retrospective cohort studies comparing NOTES with LAVH. The study
      quality as assessed by the Newcastle-Ottawa scale was acceptable. Both studies
      reported no conversions. The operative time in women treated by NOTES was shorter
      compared to LAVH: the mean difference (MD) was -22.04min (95% CI -28.00min to 
      16.08min; 342 women; 2 studies). There were no differences for complications in
      women treated by NOTES compared to LAVH: the risk ratio (RR) was 0.57 (95% CI
      0.17-1.91; 342 women; 2 studies). The length of stay was shorter in women treated
      by NOTES versus LAVH: the MD was -0.42days (95% CI -0.59days to -0.25days; 342
      women; 2 studies). There were no differences for the median VAS scores at 12h
      between women treated by NOTES (median 2, range 0-6) or by LAVH (median 2, range
      0-6) (48 women, 1 study). There were no differences in the median additional
      analgesic dose request in women treated by NOTES (median 0, range 0-6) or by LAVH
      (median 1, range 0-5) (48 women, 1 study). The hospital charges for treatment by
      NOTES were higher compared to LAVH: the mean difference was 137.00 ? (95% CI
      88.95-185.05 ?; 294 women; 1 study). CONCLUSIONS: At the present NOTES should be
      considered as a technique under evaluation for use in gynaecological surgery.
      RCTs are needed to demonstrate its effectiveness.

PMID- 27880894
TI  - Requirement for Dicer in Maintenance of Monosynaptic Sensory-Motor Circuits in
      the Spinal Cord.
AB  - In contrast to our knowledge of mechanisms governing circuit formation, our
      understanding of how neural circuits are maintained is limited. Here, we show
      that Dicer, an RNaseIII protein required for processing microRNAs (miRNAs), is
      essential for maintenance of the spinal monosynaptic stretch reflex circuit in
      which group Ia proprioceptive sensory neurons form direct connections with motor
      neurons. In postnatal mice lacking Dicer in proprioceptor sensory neurons, there
      are no obvious defects in specificity or formation of monosynaptic sensory-motor
      connections. However, these circuits degrade through synapse loss and retraction
      of proprioceptive axonal projections from the ventral spinal cord. Peripheral
      terminals are also impaired without retracting from muscle targets.
      Interestingly, despite these central and peripheral axonal defects,
      proprioceptive neurons survive in the absence of Dicer-processed miRNAs. These
      findings reveal that Dicer, through its production of mature miRNAs, plays a key
      role in the maintenance of monosynaptic sensory-motor circuits.

PMID- 27880895
TI  - p53 Regulates Progenitor Cell Quiescence and Differentiation in the Airway.
AB  - Mechanisms that regulate progenitor cell quiescence and differentiation in slowly
      replacing tissues are not fully understood. Here, we demonstrate that the tumor
      suppressor p53 regulates both proliferation and differentiation of progenitors in
      the airway epithelium. p53 loss decreased ciliated cell differentiation and
      increased the self-renewal and proliferative capacity of club progenitors,
      increasing epithelial cell density. p53-deficient progenitors generated a
      pseudostratified epithelium containing basal-like cells in vitro and putative
      bronchioalveolar stem cells in vivo. Conversely, an additional copy of p53
      increased quiescence and ciliated cell differentiation, highlighting the
      importance of tight regulation of p53 levels. Using single-cell RNA sequencing,
      we found that loss of p53 altered the molecular phenotype of progenitors and
      differentially modulated cell-cycle regulatory genes. Together, these findings
      reveal that p53 is an essential regulator of progenitor cell behavior, which
      shapes our understanding of stem cell quiescence during homeostasis and in cancer
      development.

PMID- 27880896
TI  - RNF166 Determines Recruitment of Adaptor Proteins during Antibacterial Autophagy.
AB  - Xenophagy is a form of selective autophagy that involves the targeting and
      elimination of intracellular pathogens through several recognition, recruitment,
      and ubiquitination events. E3 ubiquitin ligases control substrate selectivity in
      the ubiquitination cascade; however, systematic approaches to map the role of E3
      ligases in antibacterial autophagy have been lacking. We screened more than 600
      putative human E3 ligases, identifying E3 ligases that are required for adaptor
      protein recruitment and LC3-bacteria colocalization, critical steps in
      antibacterial autophagy. An unbiased informatics approach pinpointed RNF166 as a
      key gene that interacts with the autophagy network and controls the recruitment
      of ubiquitin as well as the autophagy adaptors p62 and NDP52 to bacteria.
      Mechanistic studies demonstrated that RNF166 catalyzes K29- and K33-linked
      polyubiquitination of p62 at residues K91 and K189. Thus, our study expands the
      catalog of E3 ligases that mediate antibacterial autophagy and identifies a
      critical role for RNF166 in this process.

PMID- 27880899
TI  - LC3C Contributes to Vpu-Mediated Antagonism of BST2/Tetherin Restriction on HIV-1
      Release through a Non-canonical Autophagy Pathway.
AB  - BST2 (bone marrow stromal antigen 2)/tetherin is a restriction factor of
      enveloped viruses, which blocks the release of viral particles. HIV-1 encodes
      proteins that antagonize this innate barrier, including the accessory protein
      Vpu. Here, we investigate whether the autophagy pathway and/or ATG proteins are
      hijacked by HIV-1 Vpu to circumvent BST2 restriction of viral release. We report
      that BST2 and Vpu are present in LC3-positive compartments. We found that Vpu
      selectively interacts with the ATG8 ortholog LC3C through the Vpu L63VEM66
      sequence. This sequence is required for Vpu to antagonize BST2 restriction. LC3C
      expression favors the removal of BST2 from the HIV-1 budding site, and thus HIV-1
      release in BST2-expressing cells. Additionally, ATG5 and beclin 1/ATG6, but not
      all the components of the autophagy pathway, act with LC3C to facilitate Vpu
      antagonism of BST2 restriction. Altogether, our data support the view that a non
      canonical autophagy pathway reminiscent of LC3-associated phagocytosis
      contributes to Vpu counteraction of BST2 restriction.

PMID- 27880898
TI  - HIV-1 Control by NK Cells via Reduced Interaction between KIR2DL2 and HLA
      C*12:02/C*14:03.
AB  - Natural killer (NK) cells control viral infection in part through the interaction
      between killer cell immunoglobulin-like receptors (KIRs) and their human
      leukocyte antigen (HLA) ligands. We investigated 504 anti-retroviral (ART)-free
      Japanese patients chronically infected with HIV-1 and identified two KIR/HLA
      combinations, KIR2DL2/HLA-C*12:02 and KIR2DL2/HLA-C*14:03, that impact
      suppression of HIV-1 replication. KIR2DL2+ NK cells suppressed viral replication
      in HLA-C*14:03+ or HLA-C*12:02+ cells to a significantly greater extent than did
      KIR2DL2- NK cells in vitro. Functional analysis showed that the binding between
      HIV-1-derived peptide and HLA-C*14:03 or HLA-C*12:02 influenced KIR2DL2+ NK cell
      activity through reduced expression of the peptide-HLA (pHLA) complex on the cell
      surface (i.e., reduced KIR2DL2 ligand expression), rather than through reduced
      binding affinity of KIR2DL2 to the respective pHLA complexes. Thus, KIR2DL2/HLA
      C*12:02 and KIR2DL2/HLA-C*14:03 compound genotypes have protective effects on
      control of HIV-1 through a mechanism involving KIR2DL2-mediated NK cell
      recognition of virus-infected cells, providing additional understanding of NK
      cells in HIV-1 infection.

PMID- 27880900
TI  - Tailored Tumor Immunogenicity Reveals Regulation of CD4 and CD8 T Cell Responses
      against Cancer.
AB  - CD4 and CD8 T cells play a pivotal role in controlling tumor growth. However, the
      interplay of both cell types and their role in tumor suppression still remain
      elusive. In this study, we investigated the regulation of CD4 and CD8 T cell
      responses to different classes of tumor-specific antigens in liver cancer mouse
      models. Tumors were induced in p19Arf-deficient mice by hydrodynamic injection of
      transposon plasmids encoding NrasG12V and pre-defined tumor antigens. This
      allowed for assessing the regulation of tumor-specific CD4 and CD8 T cell
      responses. We showed that MHC class I tumor immunogenicity was essential to
      trigger tumor-directed CD4 T cells. Tumor-specific CD8 T cell responses arose
      independently of CD4 T cells, but they required Th1-polarized CD4 T cells for
      efficient tumor suppression. Our results further indicate that the immune system
      is incapable of eliciting sufficient numbers of T cells directed against antigens
      derived from immunoedited tumors, which consequently leads to a lack of T-cell
      mediated tumor suppression in untreated hosts.

PMID- 27880897
TI  - Direct Probing of Germinal Center Responses Reveals Immunological Features and
      Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer.
AB  - Generating tier 2 HIV-neutralizing antibody (nAb) responses by immunization
      remains a challenging problem, and the immunological barriers to induction of
      such responses with Env immunogens remain unclear. Here, some rhesus monkeys
      developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2)
      whereas others did not. This was not because HIV Env trimers were immunologically
      silent because all monkeys made similar ELISA-binding antibody responses; the key
      difference was nAb versus non-nAb responses. We explored the immunological
      barriers to HIV nAb responses by combining a suite of techniques, including
      longitudinal lymph node fine needle aspirates. Unexpectedly, nAb development best
      correlated with booster immunization GC B cell magnitude and Tfh characteristics
      of the Env-specific CD4 T cells. Notably, these factors distinguished between
      successful and unsuccessful antibody responses because GC B cell frequencies and
      stoichiometry to GC Tfh cells correlated with nAb development, but did not
      correlate with total Env Ab binding titers.

PMID- 27880901
TI  - Stress Kinase GCN2 Controls the Proliferative Fitness and Trafficking of
      Cytotoxic T Cells Independent of Environmental Amino Acid Sensing.
AB  - GCN2 is one of four "stress kinases" that block translation by phosphorylating
      eIF2alpha. GCN2 is thought to bind uncharged tRNAs to "sense" amino acid
      availability. In mammals, myeloid cells expressing indoleamine dioxygenases
      locally deplete tryptophan, which is detected by GCN2 in T cells to cause
      proliferative arrest. GCN2-deficient T cells were reported to ectopically enter
      the cell cycle when tryptophan was limiting. Using GCN2-deficient strains crossed
      to T cell receptor (TCR) transgenic backgrounds, we found GCN2 is essential for
      induction of stress target genes such as CHOP. However, GCN2-deficient CD8+ T
      cells fail to proliferate in limiting tryptophan, arginine, leucine, lysine, or
      asparagine, the opposite of what previous studies concluded. In vitro and in vivo
      proliferation experiments show that GCN2-deficient CD8+ T cells have T cell
      intrinsic proliferative and trafficking defects not observed in CD4+ T cells.
      Thus, GCN2 is required for normal cytotoxic T cell function.

PMID- 27880904
TI  - LYVE1 Marks the Divergence of Yolk Sac Definitive Hemogenic Endothelium from the
      Primitive Erythroid Lineage.
AB  - The contribution of the different waves and sites of developmental hematopoiesis
      to fetal and adult blood production remains unclear. Here, we identify lymphatic
      vessel endothelial hyaluronan receptor-1 (LYVE1) as a marker of yolk sac (YS)
      endothelium and definitive hematopoietic stem and progenitor cells (HSPCs).
      Endothelium in mid-gestation YS and vitelline vessels, but not the dorsal aorta
      and placenta, were labeled by Lyve1-Cre. Most YS HSPCs and erythro-myeloid
      progenitors were Lyve1-Cre lineage traced, but primitive erythroid cells were
      not, suggesting that they represent distinct lineages. Fetal liver (FL) and adult
      HSPCs showed 35%-40% Lyve1-Cre marking. Analysis of circulation-deficient Ncx1-/-
      concepti identified the YS as a major source of Lyve1-Cre labeled HSPCs. FL
      proerythroblast marking was extensive at embryonic day (E) 11.5-13.5, but
      decreased to hematopoietic stem cell (HSC) levels by E16.5, suggesting that HSCs
      from multiple sources became responsible for erythropoiesis. Lyve1-Cre thus marks
      the divergence between YS primitive and definitive hematopoiesis and provides a
      tool for targeting YS definitive hematopoiesis and FL colonization.

PMID- 27880902
TI  - Forward Genetic Screens in Zebrafish Identify Pre-mRNA-Processing Pathways
      Regulating Early T Cell Development.
AB  - Lymphocytes represent basic components of vertebrate adaptive immune systems,
      suggesting the utility of non-mammalian models to define the molecular basis of
      their development and differentiation. Our forward genetic screens in zebrafish
      for recessive mutations affecting early T cell development revealed several major
      genetic pathways. The identification of lineage-specific transcription factors
      and specific components of cytokine signaling and DNA replication and/or repair
      pathways known from studies of immunocompromised mammals provided an evolutionary
      cross-validation of the screen design. Unexpectedly, however, genes encoding
      proteins required for pre-mRNA processing were enriched in the collection of
      mutants identified here. In both zebrafish and mice, deficiency of the splice
      regulator TNPO3 impairs intrathymic T cell differentiation, illustrating the
      evolutionarily conserved and cell-type-specific functions of certain pre-mRNA
      processing factors for T cell development.

PMID- 27880905
TI  - Semaphorin 3G Provides a Repulsive Guidance Cue to Lymphatic Endothelial Cells
      via Neuropilin-2/PlexinD1.
AB  - The vertebrate circulatory system is composed of closely related blood and
      lymphatic vessels. It has been shown that lymphatic vascular patterning is
      regulated by blood vessels during development, but its molecular mechanisms have
      not been fully elucidated. Here, we show that the artery-derived ligand
      semaphorin 3G (Sema3G) and the endothelial cell receptor PlexinD1 play a role in
      lymphatic vascular patterning. In mouse embryonic back skin, genetic inactivation
      of Sema3G or PlexinD1 results in abnormal artery-lymph alignment and reduced
      lymphatic vascular branching. Conditional ablation in mice demonstrates that
      PlexinD1 is primarily required in lymphatic endothelial cells (LECs). In vitro
      analyses show that Sema3G binds to neuropilin-2 (Nrp2), which forms a receptor
      complex with PlexinD1. Sema3G induces cell collapse in an Nrp2/PlexinD1-dependent
      manner. Our findings shed light on a molecular mechanism by which LECs are
      distributed away from arteries and form a branching network during lymphatic
      vascular development.

PMID- 27880903
TI  - miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor
      Editing during B Cell Maturation.
AB  - B cell development is a tightly regulated process dependent on sequential
      rearrangements of immunoglobulin loci that encode the antigen receptor. To
      elucidate the role of microRNAs (miRNAs) in the orchestration of B cell
      development, we ablated all miRNAs at the earliest stage of B cell development by
      conditionally targeting the enzymes critical for RNAi in early B cell precursors.
      Absence of any one of these enzymes led to a block at the pro- to pre-B cell
      transition due to increased apoptosis and a failure of pre-B cells to
      proliferate. Expression of a Bcl2 transgene allowed for partial rescue of B cell
      development, however, the majority of the rescued B cells had low surface
      immunoglobulin expression with evidence of ongoing light chain editing. Our
      analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT
      FOXO1 pathway that in turn controls Rag expression during B cell development.

PMID- 27880907
TI  - Tet3-Mediated DNA Demethylation Contributes to the Direct Conversion of
      Fibroblast to Functional Neuron.
AB  - The direct conversion of somatic cells to neurons by bypassing the multipotent
      cell state may be a powerful approach for personalized medicine. In addition to
      neuronal transcription factors and multiple small molecules, we find that
      epigenetic modification also contributes to the direct conversion of fibroblasts
      to neurons. Here, we show that Tet3, a DNA dioxygenase, can rapidly and
      efficiently convert fibroblasts directly into functional neurons. The induced
      neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and
      neuronal nuclei (NeuN). Gene expression profiles demonstrate distinct neuron
      specific gene clusters in iNs compared with primary neurons. Induced neurons
      display maturing firing patterns and form functional synapses. Additionally, we
      observe that the level of 5hmC in iNs gradually increases during the time course
      of transdifferentiation. These findings suggest that DNA demethylation may
      regulate direct lineage commitment, representing an avenue for investigating the
      process of transdifferentiation.

PMID- 27880906
TI  - Emergence of a Wave of Wnt Signaling that Regulates Lung Alveologenesis by
      Controlling Epithelial Self-Renewal and Differentiation.
AB  - Alveologenesis is the culmination of lung development and involves the correct
      temporal and spatial signals to generate the delicate gas exchange interface
      required for respiration. Using a Wnt-signaling reporter system, we demonstrate
      the emergence of a Wnt-responsive alveolar epithelial cell sublineage, which
      arises during alveologenesis, called the axin2+ alveolar type 2 cell, or
      AT2Axin2. The number of AT2Axin2 cells increases substantially during late lung
      development, correlating with a wave of Wnt signaling during alveologenesis.
      Transcriptome analysis, in vivo clonal analysis, and ex vivo lung organoid assays
      reveal that AT2sAxin2 promote enhanced AT2 cell growth during generation of the
      alveolus. Activating Wnt signaling results in the expansion of AT2s, whereas
      inhibition of Wnt signaling inhibits AT2 cell development and shunts alveolar
      epithelial development toward the alveolar type 1 cell lineage. These findings
      reveal a wave of Wnt-dependent AT2 expansion required for lung alveologenesis and
      maturation.

PMID- 27880908
TI  - Conditional Loss of Pten in Myogenic Progenitors Leads to Postnatal Skeletal
      Muscle Hypertrophy but Age-Dependent Exhaustion of Satellite Cells.
AB  - Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a
      quiescent (G0) state. Muscle injury not only activates SCs locally, but also
      alerts SCs in distant uninjured muscles via circulating factors. The resulting
      GAlert SCs are adapted to regenerative cues and regenerate injured muscles more
      efficiently, but whether they provide any long-term benefits to SCs is unknown.
      Here, we report that embryonic myogenic progenitors lacking the phosphatase and
      tensin homolog (Pten) exhibit enhanced proliferation and differentiation,
      resulting in muscle hypertrophy but fewer SCs in adult muscles. Interestingly,
      Pten null SCs are predominantly in the GAlert state, even in the absence of an
      injury. The GAlert SCs are deficient in self-renewal and subjected to accelerated
      depletion during regeneration and aging and fail to repair muscle injury in old
      mice. Our findings demonstrate a key requirement of Pten in G0 entry of SCs and
      provide functional evidence that prolonged GAlert leads to stem cell depletion
      and regenerative failure.

PMID- 27880909
TI  - Nfix Induces a Switch in Sox6 Transcriptional Activity to Regulate MyHC-I
      Expression in Fetal Muscle.
AB  - Sox6 belongs to the Sox gene family and plays a pivotal role in fiber type
      differentiation, suppressing transcription of slow-fiber-specific genes during
      fetal development. Here, we show that Sox6 plays opposite roles in MyHC-I
      regulation, acting as a positive and negative regulator of MyHC-I expression
      during embryonic and fetal myogenesis, respectively. During embryonic myogenesis,
      Sox6 positively regulates MyHC-I via transcriptional activation of Mef2C, whereas
      during fetal myogenesis, Sox6 requires and cooperates with the transcription
      factor Nfix in repressing MyHC-I expression. Mechanistically, Nfix is necessary
      for Sox6 binding to the MyHC-I promoter and thus for Sox6 repressive function,
      revealing a key role for Nfix in driving Sox6 activity. This feature is
      evolutionarily conserved, since the orthologs Nfixa and Sox6 contribute to
      repression of the slow-twitch phenotype in zebrafish embryos. These data
      demonstrate functional cooperation between Sox6 and Nfix in regulating MyHC-I
      expression during prenatal muscle development.

PMID- 27880910
TI  - CDK12 Inhibition Reverses De Novo and Acquired PARP Inhibitor Resistance in BRCA
      Wild-Type and Mutated Models of Triple-Negative Breast Cancer.
AB  - Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous
      recombination (HR)-deficient cancers, their utility is limited by acquired
      resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor
      of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent
      activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple
      negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs),
      dinaciclib ablates restored HR and reverses PARP inhibitor resistance.
      Additionally, we show that de novo resistance to PARP inhibition in BRCA1-mutated
      cell lines and a PDX derived from a PARP-inhibitor-naive BRCA1 carrier is
      mediated by residual HR and is reversed by CDK12 inhibition. Finally, dinaciclib
      augments the degree of response in a PARP-inhibitor-sensitive model, converting
      tumor growth inhibition to durable regression. These results highlight the
      significance of HR disruption as a therapeutic strategy and support the broad use
      of combined CDK12 and PARP inhibition in TNBC.

PMID- 27880911
TI  - USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by
      Deubiquitinating Histone H2B.
AB  - Decreased expression of the USP44 deubiquitinase has been associated with global
      increases in H2Bub1 levels during mouse embryonic stem cell (mESC)
      differentiation. However, whether USP44 directly deubiquitinates histone H2B or
      how its activity is targeted to chromatin is not known. We identified USP44 as an
      integral subunit of the nuclear receptor co-repressor (N-CoR) complex. USP44
      within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44
      impairs the repressive activity of the N-CoR complex. Chromatin
      immunoprecipitation (ChIP) experiments confirmed that USP44 recruitment reduces
      H2Bub1 levels at N-CoR target loci. Furthermore, high expression of USP44
      correlates with reduced levels of H2Bub1 in the breast cancer cell line MDA-MB
      231. Depletion of either USP44 or TBL1XR1 impairs the invasiveness of MDA-MB-231
      cells in vitro and causes an increase of global H2Bub1 levels. Our findings
      indicate that USP44 contributes to N-CoR functions in regulating gene expression
      and is required for efficient invasiveness of triple-negative breast cancer
      cells.

PMID- 27880912
TI  - CENP-A Is Dispensable for Mitotic Centromere Function after Initial
      Centromere/Kinetochore Assembly.
AB  - Human centromeres are defined by chromatin containing the histone H3 variant CENP
      A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete
      degradation of endogenous CENP-A, we now demonstrate that once the first steps of
      centromere assembly have been completed in G1/S, continued CENP-A binding is not
      required for maintaining kinetochore attachment to centromeres or for centromere
      function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly
      is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby
      producing defective kinetochores and failure of chromosome segregation. Without
      the continuing presence of CENP-A, CENP-B binding to alphoid DNA sequences
      becomes essential to preserve anchoring of CENP-C and the kinetochore to each
      centromere. Thus, there is a reciprocal interdependency of CENP-A chromatin and
      the underlying repetitive centromere DNA sequences bound by CENP-B in the
      maintenance of human chromosome segregation.

PMID- 27880913
TI  - mDia and ROCK Mediate Actin-Dependent Presynaptic Remodeling Regulating Synaptic
      Efficacy and Anxiety.
AB  - Here, we show neuronal inactivation-induced presynaptic remodeling and
      involvement of the mammalian homolog of Diaphanous (mDia) and Rho-associated
      coiled-coil-containing kinase (ROCK), Rho-regulated modulators of actin and
      myosin, in this process. We find that social isolation induces inactivation of
      nucleus accumbens (NAc) neurons associated with elevated anxiety-like behavior,
      and that mDia in NAc neurons is essential in this process. Upon inactivation of
      cultured neurons, mDia induces circumferential actin filaments around the edge of
      the synaptic cleft, which contract the presynaptic terminals in a ROCK-dependent
      manner. Social isolation induces similar mDia-dependent presynaptic contraction
      at GABAergic synapses from NAc neurons in the ventral tegmental area (VTA)
      associated with reduced synaptic efficacy. Optogenetic stimulation of NAc neurons
      rescues the anxiety phenotype, and injection of a specific ROCK inhibitor, Y
      27632, into the VTA reverses both presynaptic contraction and the behavioral
      phenotype. mDia-ROCK signaling thus mediates actin-dependent presynaptic
      remodeling in inactivated NAc neurons, which underlies synaptic plasticity in
      emotional behavioral responses.

PMID- 27880914
TI  - Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation,
      Memory Formation, and Genomic Structure of BDNF and Arc.
AB  - CCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure
      and regulates gene expression. Genetic studies have implicated mutations in CTCF
      in intellectual disabilities. However, the role of CTCF-mediated chromatin
      structure in learning and memory is unclear. We show that depletion of CTCF in
      postmitotic neurons, or depletion in the hippocampus of adult mice through viral
      mediated knockout, induces deficits in learning and memory. These deficits in
      learning and memory at the beginning of adulthood are correlated with impaired
      long-term potentiation and reduced spine density, with no changes in basal
      synaptic transmission and dendritic morphogenesis and arborization. Cognitive
      disabilities are associated with downregulation of cadherin and learning-related
      genes. In addition, CTCF knockdown attenuates fear-conditioning-induced
      hippocampal gene expression of key learning genes and loss of long-range
      interactions at the BDNF and Arc loci. This study thus suggests that CTCF
      dependent gene expression regulation and genomic organization are regulators of
      learning and memory.

PMID- 27880917
TI  - Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse
      Mitotic Regulators.
AB  - Reversible phosphorylation is a fundamental regulatory mechanism, intricately
      coordinated by kinases and phosphatases, two classes of enzymes widely disrupted
      in human disease. To better understand the functions of the relatively
      understudied phosphatases, we have used complementary affinity purification and
      proximity-based interaction proteomics approaches to generate a physical
      interactome for 140 human proteins harboring phosphatase catalytic domains. We
      identified 1,335 high-confidence interactions (1,104 previously unreported),
      implicating these phosphatases in the regulation of a variety of cellular
      processes. Systematic phenotypic profiling of phosphatase catalytic and
      regulatory subunits revealed that phosphatases from every evolutionary family
      impinge on mitosis. Using clues from the interactome, we have uncovered
      unsuspected roles for DUSP19 in mitotic exit, CDC14A in regulating microtubule
      integrity, PTPRF in mitotic retraction fiber integrity, and DUSP23 in centriole
      duplication. The functional phosphatase interactome further provides a rich
      resource for ascribing functions for this important class of enzymes.

PMID- 27880918
TI  - Adsorption of As(III) on porous hematite synthesized from goethite concentrate.
AB  - Arsenite (As(III)) is toxic in drinking water, which becomes an environmental
      concern worldwide. This work was to synthesize porous hematite through the
      calcination of natural goethite concentrate for As(III) adsorption, including
      adsorption kinetics, isotherms and the influence of pH and temperature. The
      calcination was performed at 300  degrees C for 180 min, producing porous
      hematite with large amount of micropores. The maximum adsorption capacity of
      As(III) on porous hematite was achieved at pH 6.0 and 25  degrees C, about 14.46
      mg g-1, compared with 2.965 mg g-1 on the original goethite concentrate. The
      improvement might be attributed to the formation of micropores and thus the
      increase in the surface area. Also, it was found that the adsorption was strongly
      pH dependent and reduced with increasing temperature. It is indicated that the
      low-cost porous hematite has great potential in As(III) removal from contaminated
      water.

PMID- 27880916
TI  - NRL-Regulated Transcriptome Dynamics of Developing Rod Photoreceptors.
AB  - Gene regulatory networks (GRNs) guiding differentiation of cell types and cell
      assemblies in the nervous system are poorly understood because of inherent
      complexities and interdependence of signaling pathways. Here, we report
      transcriptome dynamics of differentiating rod photoreceptors in the mammalian
      retina. Given that the transcription factor NRL determines rod cell fate, we
      performed expression profiling of developing NRL-positive (rods) and NRL-negative
      (S-cone-like) mouse photoreceptors. We identified a large-scale, sharp transition
      in the transcriptome landscape between postnatal days 6 and 10 concordant with
      rod morphogenesis. Rod-specific temporal DNA methylation corroborated gene
      expression patterns. De novo assembly and alternative splicing analyses revealed
      previously unannotated rod-enriched transcripts and the role of NRL in transcript
      maturation. Furthermore, we defined the relationship of NRL with other
      transcriptional regulators and downstream cognate effectors. Our studies provide
      the framework for comprehensive system-level analysis of the GRN underlying the
      development of a single sensory neuron, the rod photoreceptor.

PMID- 27880915
TI  - Blunted mGluR Activation Disinhibits Striatopallidal Transmission in Parkinsonian
      Mice.
AB  - The prevailing circuit model predicts that hyperactivity of the striatopallidal
      pathway and subsequently increased inhibition of external globus pallidus (GPe)
      neurons lead to the hypokinetic symptoms of Parkinson's disease (PD). It is
      believed that hyperactivity of the striatopallidal pathway is due to inactivity
      of dopamine receptors on the somatodendritic membrane of striatopallidal neurons,
      but the exact cellular underpinnings remain unclear. In this study, we show that
      mouse GPe astrocytes critically control ambient glutamate level, which in turn
      gates striatopallidal transmission via the activation of presynaptic metabotropic
      glutamate receptors. This presynaptic inhibition of striatopallidal transmission
      is diminished after the chronic loss of dopamine. Elevation of intracellular
      glutamate content in astrocytes restores the proper regulation of the
      striatopallidal input in PD models. These findings argue that astrocytes are key
      regulators of the striatopallidal synapse. Targeting this cell class may serve as
      an alternative therapeutic strategy for PD.

PMID- 27880920
TI  - Peroxidases from root exudates of Medicago sativa and Sorghum bicolor: Catalytic
      properties and involvement in PAH degradation.
AB  - Peroxidases from root exudates of sorghum (Sorghum bicolor L. Moench) and alfalfa
      (Medicago sativa L.) were purified and characterized, and their ability to
      oxidize native PAHs and PAH-derivatives was evaluated. The obtained data confirm
      that peroxidases are involved in the rhizosphere degradation of PAHs.
      Nondenaturing PAGE showed that the peroxidases of both plants were represented by
      a range of isoforms/isoenzymes (five to eight). Minor forms were lost during
      further purification, and as a result, the major anionic form from alfalfa root
      exudates and the major cationic form from those of sorghum were obtained. Both
      electrophoretically homogeneous peroxidases were monomeric proteins with a
      molecular weight of about 46-48 kDa. The pH optima and the main catalytic
      constants for the test substrates were determined. On the basis of their
      molecular and catalytic properties, the obtained enzymes were found to be typical
      plant peroxidases. Derivatives of PAHs and potential products of their microbial
      degradation (9-phenanthrol and 9,10-phenanthrenequinone), unlike the parent PAH
      (phenanthrene), inhibited the catalytic activity of the peroxidases, possibly
      indicating greater availability of the enzymes' active centers to these
      substances. Peroxidase-catalyzed decreases in the concentrations of a number of
      PAHs and their derivatives were observed. Sorghum peroxidase oxidized anthracene
      and phenanthrene, while alfalfa peroxidase oxidized only phenanthrene. 1-Hydroxy
      2-naphthoic acid was best oxidized by peroxidase of alfalfa. However, quinone
      derivatives of PAHs were unavailable to sorghum peroxidase, but were oxidized by
      alfalfa peroxidase. These results indicate that the major peroxidases from root
      exudates of alfalfa and sorghum can have a role in the rhizosphere degradation of
      PAHs.

PMID- 27880919
TI  - Activation of G protein-coupled receptor 30 by thiodiphenol promotes
      proliferation of estrogen receptor alpha-positive breast cancer cells.
AB  - Many studies have been shown that environmental estrogen bisphenol A (BPA) can
      activate nuclear receptor (estrogen receptor alpha, ERalpha) or membrane receptor
      (G-protein-coupled receptor, GPR30) in breast cancer cells and exerts genomic or
      nongenomic actions inducing cell proliferation. 4,4'-thiodiphenol (TDP) as one of
      BPA derivatives exhibits more potent estrogenic activity than BPA does. However,
      comparatively little is known about the ways in which TDP interferes with these
      signaling pathways and produces cell biological changes. This study evaluated the
      effect of TDP on cell viability, reactive oxygen species (ROS) formation, and
      intercellular calcium (Ca2+) fluctuation in MCF-7 breast cancer cells. The
      underlying molecular mechanism of cell proliferation induced by TDP was analyzed
      by examining the activation of ERalpha and GPR30-mediated phosphatidylinotidol 3
      kinase/protein kinase B (PI3K/AKT) and extracellular-signa1regulated kinase
      (ERK1/2) signaling pathways. The results showed that exposure to 0.1-10 MUM TDP
      for 24, 48, and 72 h significantly increased viability of MCF-7 cells. At the
      same concentration range, TDP exposure for 3 and 24 h markedly elevated ROS
      production and intracellular Ca2+ levels. In addition, 0.01-1 MUM TDP
      significantly increased the expression of ERalpha, GPR30, p-AKT and p-ERK1/2
      protein. Specific protein inhibitors blocked phosphorylation of ERK1/2 and AKT
      and decreased TDP-induced cell proliferation. These findings show that TDP
      activated the GPR30-PI3K/AKT and ERK1/2 pathways, and the resulting interaction
      with ERalpha stimulated MCF-7 cell proliferation. Our results indicate a novel
      mechanism through which TDP may exert relevant estrogenic action in ERalpha
      positive cancer cells.

PMID- 27880921
TI  - Determination of the gut retention of plastic microbeads and microfibers in
      goldfish (Carassius auratus).
AB  - Microplastics are ubiquitous pollutants in aquatic habitats and commonly found in
      the gut contents of fish yet relatively little is known about the retention of
      these particles by fish. In this study, goldfish were fed a commercial fish food
      pellet amended with 50 particles of one of two microplastics types, microbeads
      and microfibers. Microbeads were obtained from a commercial facial cleanser while
      microfibers were obtained from washed synthetic textile. Following consumption of
      the amended pellet, fish were allowed to feed to satiation on non-amended food
      followed by fasting for periods ranging from 1.5 h to 6 days. Fish sacrificed at
      different time points were dissected to remove gut contents and the digesta
      contents retention and microplastic retention was determined. Although a small
      number of microplastic particles were retained in fish GI-tracts after 6 days (0
      3 particles/50), the retention of microplastics was generally similar to the
      retention of bulk digesta contents. According to a breakpoint regression model
      fitted to digesta contents and microplastic particles, the 50% and 90% evacuation
      times were 10 h and 33.4 h, respectively. The results of this study indicate that
      neither microbeads nor microfibers are likely to accumulate within the gut
      contents of fish over successive meals.

PMID- 27880922
TI  - Genotoxicity induced by water and sediment samples from a river under the
      influence of brewery effluent.
AB  - Brewery effluents contain complex mixtures that are discharged into rivers.
      Therefore, it is necessary to evaluate the genotoxic potential of these
      effluents. The study evaluated the genotoxicity of surface water and sediment
      samples from the Jacui River in the state of Rio Grande do Sul, Brazil, which
      received effluents discharged from a brewery. The Salmonella/microsome test,
      Comet Assay and Micronucleus test on V79 cells, as well as the element profile
      (PIXE) and PAHs levels were used for this purpose. The surface water and sediment
      samples were collected in summer at three sites: 1 km upstream from the brewery
      discharge site (Site A); in front of the effluent discharge site, after chemical
      and biological treatment (Site B); about 1 km downstream from the discharge site
      (Site C). Only a sediment sample from Site A induced a mutagenic effect using the
      Salmonella/microsoma test (TA97a). All three sites presented genotoxicity (A, B
      and C), both for water and sediments using comet assay, and mutagenicity in the
      samples from Site B (surface water) and Site A and Site C (sediments) using the
      micronuclei tests. The results of PIXE and PAHs showed higher levels of elements
      for samples obtained from sites upstream and downstream from the effluent
      discharge. Environmental samples consist of complex mixtures of chemicals, and it
      is difficult to associate DNA damage with a specific element. This study showed
      that brewery effluent contains metals and PAHs that can induce in vitro
      genotoxicity under the conditions of this study.

PMID- 27880923
TI  - In situ speciation of uranium in treated acid mine drainage using the diffusion
      gradients in thin films technique (DGT).
AB  - The exchange membranes P81 and DE81 and Chelex-100 resin were used to perform in
      situ speciation of uranium in treated acid mine drainage at the Osamu Utsumi
      mining site, Pocos de Caldas city, Southeast Brazil. To investigate possible
      chemical modifications in the samples during analysis, the three ligands were
      deployed in situ and in a laboratory (in lab). The results obtained in situ were
      also compared to a speciation performed using Visual MINTEQ software. Chelex-100
      retained total labile U for a period of up to 48 h. The labile U fraction
      determined by Chelex 100 ranged from 107 +/- 6% to 147 +/- 44% in situ and from
      115 +/- 22% to 191 +/- 5% in lab. DE81 retained anionic U species up to 8 h, with
      labile fractions ranging from 37 +/- 2% to 76 +/- 3% in situ and 34 +/- 12% to
      180 +/- 17% in lab. P81 exhibited a lower efficiency in retaining U species, with
      concentrations ranging from 6+/- 2% to 19+/- 2% in situ and 3+/- 2% to 18+/- 2%
      in lab. The speciation obtained from MINTEQ suggests that the major U species
      were UO2OH+, UO2(OH)3-, UO2(OH)2(aq), Ca2UO2(CO3)3(aq), CaUO2(CO3)32-, UO2(CO3)22
      , and UO2(CO3)34-. This result is in accordance with the results obtained in
      situ. Differences concerning speciation and the total and soluble U
      concentrations were observed between the deployments performed in situ and in the
      laboratory, indicating that U speciation must be performed in situ.

PMID- 27880924
TI  - Pb2+ ions mobility perturbation by iron particles during electrokinetic
      remediation of contaminated soil.
AB  - Electrokinetic (EK) remediation is one of the most useful approaches for de
      contamination of soils. However, it is unclear that how and when the
      electrokinetic remediation gives advantages over other remediation techniques in
      soil. This study was designed to find the influence of Fe2+ particles on the
      mobility of Pb2+ ions, during electrokinetic remediation, in soil contaminated
      purposely by lead nitrate Pb(NO3)2. Two types of electrokinetic experiments were
      performed, by using iron and graphite electrodes. The Fe2+ ions from the iron
      electrodes, produced due to acidic environment in anode compartment, affected the
      mobility of lead particles by precipitating as Fe(OH)2. Fe2+ ions enhance the
      adsorption of lead ions in soil. The results show Fe2+ ions of lower ionic
      conductivity decreased mobility of other particles in soil. Electrokinetic
      remediation for up to 120 h with iron electrodes is shown to be less effective
      for removal of lead. In contrast, graphite electrodes were 15 times more
      effective in lead removal from soil.

PMID- 27880925
TI  - Developmental bisphenol A exposure impairs sperm function and reproduction in
      zebrafish.
AB  - The developmental and reproductive toxicity of bisphenol A (BPA) has been
      demonstrated in a variety of model systems. Zebrafish (Danio rerio) were
      waterborne-exposed to BPA during three different developmental stages: embryonic
      period:6 h post fertilization (hpf) to 5 months post fertilization (mpf); larval
      period: 6 days post fertilization (dpf) to 5 mpf; and sexually mature period: 3
      mpf to 5 mpf. Evaluations included F0 adult growth, reproduction parameters, and
      F1 offspring development. BPA exposure did not affect zebrafish growth in any of
      exposure groups. Testis weight was decreased only following the 6 hpf to 5 mpf
      0.001 MUM BPA exposure. The lowest effect level indicated by a reduction in sperm
      volume, density, motility, and velocity across a range of exposure durations was
      0.001 MUM, with all but sperm density significant for the longest exposure
      duration, which was also the only significant endpoint for the lowest exposure
      concentration in the 3-5 mpf exposure group. Nonmonotonic concentration-response
      curves were noted for all F0 reproductive endpoints for at least one of the two
      longest exposure durations. For the F1 offspring of fish exposed from 6 hpf to 5
      mpf, malformations and mortality were increased following 0.001 MUM BPA exposure,
      while egg production and fertilization were reduced in higher concentration
      treatment groups. Overall, BPA exposure during three different developmental
      periods impaired zebrafish reproductive development, with most significance
      changes found in the lowest concentration treatment groups. Genetic impacts on
      gamete development may underlie the secondary effects of reduced fertilization
      rate, embryonic mortality, and malformations.

PMID- 27880926
TI  - Release of heavy metals during long-term land application of sewage sludge
      compost: Percolation leaching tests with repeated additions of compost.
AB  - Leaching assessment procedures have been used to determine the leachability of
      heavy metals as input for evaluating the risk from sewage sludge compost land
      application. However, relatively little attention has been paid to understanding
      leaching from soils with repeated application of sewage sludge compost with
      elevated levels of heavy metals. In this paper, leaching assessment is extended
      to evaluate the potential leaching of heavy metals during repetitive application
      of composted sewage sludge to soils. Four cycling of compost additions and
      percolation leaching were conducted to investigate how leaching behavior of heavy
      metals changed with repeated additions of compost. Results showed that repetitive
      additions of compost to soil significantly increased the content of organic
      matter, which favored the formation of reducing condition due to improved
      microbial activities and oxygen consumption. Establishment of reducing conditions
      can enhance the leaching concentrations of As by approximately 1 order of
      magnitude, especially for the soil rich in organic matter. For Cd, Cr, Cu, and
      Pb, repeated additions of compost will cause accumulation in total contents but
      not enhancement in leaching concentrations. The infiltration following compost
      additions will leach out the mobile fraction and the residual fraction might not
      release in the next cycling of compost addition and infiltration. The cumulative
      release of Cd, Cr, Cu, and Pb accounted for less than 5% of the total contents
      during four times of compost applications.

PMID- 27880927
TI  - Very low risk ST-segment elevation myocardial infarction? It exists and may be
      easily identified.
AB  - BACKGROUND: Early discharge protocols have been proposed for ST-segment elevation
      myocardial infarction (STEMI) low risk patients despite the existence of few but
      significant cardiovascular events during mid-term follow-up. We aimed to identify
      a subgroup of patients among those considered low-risk in which prognosis would
      be particularly good. METHODS: We analyzed 30-day outcomes and long-term follow
      up among 1.111 STEMI patients treated with reperfusion therapy. RESULTS:
      Multivariate analysis identified seven variables as predictors of 30-day
      outcomes: Femoral approach; age>65; systolic dysfunction; postprocedural TIMI
      flow<3; elevated creatinine level>1.5mg/dL; stenosis of left-main coronary
      artery; and two or higher Killip class (FASTEST). A total of 228 patients
      (20.5%), defined as very low-risk (VLR), had none of these variables on
      admission. VLR group of patients compared to non-VLR patients had lower in
      hospital (0% vs. 5.9%; p<0.001) and 30-day mortality (0% vs. 6.25%: p<0.001).
      They also presented fewer in-hospital complications (6.6% vs. 39.7%; p<0.001) and
      30-day major adverse events (0.9% vs. 4.5%; p=0.01). Significant mortality
      differences during a mean follow-up of 23.8+/-19.4months were also observed (2.2%
      vs. 15.2%; p<0.001). The first VLR subject died 11months after hospital
      discharge. No cardiovascular deaths were identified in this subgroup of patients
      during follow-up. CONCLUSIONS: About a fifth of STEMI patients have VLR and can
      be easily identified. They have an excellent prognosis suggesting that 24-48h in
      hospital stay could be a feasible alternative in these patients.

PMID- 27880929
TI  - A complicated case of amyand's hernia involving a perforated appendix and its
      management using minimally invasive laparoscopic surgery: A case report.
AB  - INTRODUCTION: Amyand's hernia is a rare condition of inguinal hernia in which the
      appendix is incarcerated within the hernia sac through the internal ring.
      Complications include acute appendicitis and perforated appendicitis, which are
      rare in incidence, accounting for about 0.1% of cases.1 These complications prove
      a diagnostic challenge due to their vague clinical presentation and atypical
      laboratory and radiological findings. Until recently, open appendectomy was the
      mainstay of treatment. Laparoscopic surgery offers a less invasive approach to
      confirming a diagnosis and serving as a therapeutic tool in equivocal cases. CASE
      PRESENTATION: We report a case of a previously healthy 20-year-old male
      presenting with atypical signs and symptoms, as well as blood investigation
      results, and radiological findings of a perforated appendix within an Amyand's
      hernia. The patient was successfully managed using a minimally invasive
      laparoscopic appendectomy approach. DISCUSSION: Until recently, open appendectomy
      was considered the mainstay in the management of complicated Amyand's hernia.
      Laparoscopic surgery provides a new avenue for dealing with diagnostic
      uncertainty with advantages including faster recovery time, reduced hospital
      stay, and better quality of life. CONCLUSION: This case report highlights the
      concealing effects of an Amyand's hernia on a perforated appendix, the
      considerations required when an equivocal diagnosis present and the safe use of
      the minimally invasive laparoscopic surgery in the treatment of this rare
      condition.

PMID- 27880928
TI  - Determination of red blood cell fatty acid profiles: Rapid and high-confident
      analysis by chemical ionization-gas chromatography-tandem mass spectrometry.
AB  - Cellular fatty acid (FA) profiles have been acknowledged as biomarkers in various
      human diseases. Nevertheless, common FA analysis by gas chromatography mass
      spectrometry (GC-MS) requires long analysis time. Hence, there is a need for
      feasible methods for high throughput analysis in clinical studies. FA was
      extracted from red blood cells (RBC) and derivatized to fatty acid methyl esters
      (FAME). A method using gas chromatography tandem mass spectrometry (GC-MS/MS)
      with ammonia-induced chemical ionization (CI) was developed for the analysis of
      FA profiles in human RBC. We compared this method with classical single GC-MS
      using electron impact ionization (EI). The FA profiles of 703 RBC samples were
      determined by GC-MS/MS. In contrast to EI ammonia-induced CI resulted in adequate
      amounts of molecular ions for further fragmentation of FAME. Specific fragments
      for confident quantification and fragmentation were determined for 45 FA. The GC
      MS/MS method has a total run time of 9min compared to typical analysis times of
      up to 60min in conventional GC-MS. Intra and inter assay variations were <10% for
      all FA analyzed. Analysis of RBC FA composition revealed an age-dependent
      increase of the omega-3 eicosapentaenoic and docosahexaenoic acid, and a decline
      of the omega-6 linoleic acid with a corresponding rise of the omega-3 index. The
      combination of ammonia-induced CI and tandem mass spectrometry after GC
      separation allows for high-throughput, robust and confident analysis of FA
      profiles in the clinical laboratory.

PMID- 27880930
TI  - Lactate dehydrogenase is a prognostic indicator in patients with hepatocellular
      carcinoma treated by sorafenib: results from the real life practice in HBV
      endemic area.
AB  - PURPOSE: Lactate dehydrogenase (LDH), which was an indirect marker of hypoxia,
      was a potentially prognostic factor in several malignancies. There is a lack of
      evidence about the prognostic value of serum LDH level in patients with
      hepatocellular carcinoma (HCC) receiving sorafenib treatment from hepatitis B
      virus endemic areas. MATERIALS AND METHODS: A total of 119 HBV-related HCC
      patients treated by sorafenib from a Chinese center were included into the study.
      They were categorized into 2 groups according to the cut-off value of pre
      treatment LDH, which was determined by the time dependent receiver operating
      characteristics (ROC) curve for the overall survival. The prognostic value of LDH
      was evaluated. The relationships between LDH and other clinicopathological
      factors were also assessed. RESULTS: The cut-off value was 221 U/L. With a median
      follow up of 15 (range, 3-73) months, 91 patients reached the endpoint.
      Multivariate analysis proved that pre-treatment serum LDH level was an
      independent prognostic factor for both overall survival (OS) and progression-free
      survival (PFS). For patients whose pre-treatment LDH >= 221 U/L, increased LDH
      value after 3 months of sorafenib treatment predicted inferior OS and PFS. And
      patients with elevated pre-treatment LDH level predisposed to be featured with
      lower serum albumin, presence of macroscopic vascular invasion, advanced Child
      Pugh class, advanced T category, higher AFP, and higher serum total bilirubin.
      CONCLUSIONS: Serum LDH level was a potentially prognostic factor in HCC patients
      treated by sorafenib in HBV endemic area. More relevant studies with reasonable
      study design are needed to further strengthen its prognostic value.

PMID- 27880932
TI  - Lgr6+ stem cells and their progeny in mouse epidermis under regimens of exogenous
      skin carcinogenesis, and their absence in ensuing skin tumors.
AB  - Lgr6+ cells have been identified as a novel class of proliferating (Ki67+) stem
      cells in mouse epidermis. We investigated their response to UV exposure in Lgr6
      EGFP-Ires-CreERT2/R26R-LacZ haired and hairless mice and whether they become
      initiating cells of UV- or chemically induced skin tumors. UV overexposure erased
      Lgr6+ cells (EGFP+) from the interfollicular epidermis (IFE), but - as after
      wounding - they apparently repopulated the IFE from the hair follicles. Under sub
      sunburn chronic UV exposure, Lgr6+ cells and their progeny (LacZ+ after pulse of
      tamoxifen) diminished strongly in the IFE. Although the inter-tumoral IFE clearly
      showed Lgr6 progeny, none of the UV- or chemically induced tumors (n = 22 and 41,
      respectively) appeared to be clonal expansions of Lgr6+ stem cells; i.e. no Lgr6+
      cells or progeny in the proliferating tumor bulk. In checking for promoter
      methylation we found it to occur stochastically for the EGFP-Cre cassette. Lgr6
      mRNA measured by qPCR was found to be diminished in skin tumors (also in UV
      tumors from wt type mice). The ratio of Lgr6/Ki67 was significantly reduced,
      pointing at a loss of Lgr6+ cells from the proliferative pool. Our data show that
      Lgr6+ cells are not major tumor-initiating cells in skin carcinogenesis.

PMID- 27880931
TI  - An XIST-related small RNA regulates KRAS G-quadruplex formation beyond X
      inactivation.
AB  - X-inactive-specific transcript (XIST), a long non-coding RNA, is essential for
      the initiation of X-chromosome inactivation. However, little is known about other
      roles of XIST in the physiological process in eukaryotic cells. In this study,
      the bioinformatics approaches revealed XIST could be processed into a small non
      coding RNA XPi2. The XPi2 RNA was confirmed by a northern blot assay; its
      expression was gender-independent, suggesting the role of XPi2 was beyond X
      chromosome inactivation. The pull-down assay combined with LC-MS-MS identified
      two XPi2-associated proteins, nucleolin and hnRNP A1, connected to the formation
      of G-quadruplex. Moreover, the microarray data showed the knockdown of XPi2 down
      regulated the KRAS pathway. Consistently, we tested the expression of ten genes,
      including KRAS, which was correlated with a G-quadruplex formation and found the
      knockdown of XPi2 caused a dramatic decrease in the transcription level of KRAS
      among the ten genes. The results of CD/NMR assay also supported the interaction
      of XPi2 and the polypurine-polypyrimidine element of KRAS. Accordingly, XPi2 may
      stimulate the KRAS expression by attenuating G-quadruplex formation. Our present
      work sheds light on the novel role of small RNA XPi2 in modulating the G
      quadruplex formation which may play some essential roles in the KRAS- associated
      carcinogenesis.

PMID- 27880934
TI  - Tumors with unmethylated MLH1 and the CpG island methylator phenotype are
      associated with a poor prognosis in stage II colorectal cancer patients.
AB  - We previously developed a novel tumor subtype classification model for duodenal
      adenocarcinomas based on a combination of the CpG island methylator phenotype
      (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this
      model in stage II colorectal cancer (CRC) patients. Tumors were assigned to
      CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U,
      or CIMP-/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin
      production differed among the four patient subgroups, and CIMP+/MLH1-U tumors
      were more likely to have lymphovascular invasion and mucin production. Kaplan
      Meier analyses revealed differences in both disease-free survival (DFS) and
      overall survival (OS) among the four groups. In a multivariate analysis,
      CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS
      were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that
      tumor subtype classification based on the combination of CIMP and MLH1
      methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U
      tumors exhibit aggressive features and are associated with poor clinical
      outcomes.

PMID- 27880933
TI  - Immunological effects of nilotinib prophylaxis after allogeneic stem cell
      transplantation in patients with advanced chronic myeloid leukemia or
      philadelphia chromosome-positive acute lymphoblastic leukemia.
AB  - Allogeneic stem cell transplantation remains the standard treatment for resistant
      advanced chronic myeloid leukemia and Philadelphia chromosome-positive acute
      lymphoblastic leukemia. Relapse is the major cause of treatment failure in both
      diseases. Post-allo-SCT administration of TKIs could potentially reduce relapse
      rates, but concerns regarding their effect on immune reconstitution have been
      raised. We aimed to assess immune functions of 12 advanced CML and Ph+ ALL
      patients who received post-allo-SCT nilotinib. Lymphocyte subpopulations and
      their functional activities including T-cell response to mitogens, NK cytotoxic
      activity and thymic function, determined by quantification of the T cell receptor
      (TCR) excision circles (TREC) and TCR repertoire, were evaluated at several time
      points, including pre-nilotib-post-allo-SCT, and up to 365 days on nilotinib
      treatment. NK cells were the first to recover post allo-SCT. Concomitant to
      nilotinib administration, total lymphocyte counts and subpopulations gradually
      increased. CD8 T cells were rapidly reconstituted and continued to increase until
      day 180 post SCT, while CD4 T cells counts were low until 180-270 days post
      nilotinib treatment. T-cell response to mitogenic stimulation was not inhibited
      by nilotinib administration. Thymic activity, measured by TREC copies and surface
      membrane expression of 24 different TCR Vbeta families, was evident in all
      patients at the end of follow-up after allo-SCT and nilotinib treatment. Finally,
      nilotinib did not inhibit NK cytotoxic activity. In conclusion, administration of
      nilotinib post allo-SCT, in attempt to reduce relapse rates or progression of Ph+
      ALL and CML, did not jeopardize immune reconstitution or function following
      transplantation.

PMID- 27880936
TI  - Dietary grape seed proanthocyanidins (GSPs) improve weaned intestinal microbiota
      and mucosal barrier using a piglet model.
AB  - Proanthocyanidins have been suggested as an effective antibiotic alternative,
      however their mechanisms are still unknown. The present study investigated the
      effects of grape seed proanthocyanidins on gut microbiota and mucosal barrier
      using a weaned piglet model in comparison with colistin. Piglets weaned at 28 day
      were randomly assigned to four groups treated with a control ration, or
      supplemented with 250 mg/kg proanthocyanidins, kitasamycin/colistin, or 250 mg/kg
      proanthocyanidins and half-dose antibiotics, respectively. On day 28, the gut
      chyme and tissue samples were collected to test intestinal microbiota and barrier
      function, respectively. Proanthocyanidins treated piglets had better growth
      performance and reduced diarrhea incidence (P < 0.05), accompanied with decreased
      intestinal permeability and improved mucosal morphology. Gene sequencing analysis
      of 16S rRNA revealed that dietary proanthocyanidins improved the microbial
      diversity in ileal and colonic digesta, and the most abundant OTUs belong to
      Firmicutes and Bacteroidetes spp.. Proanthocyanidins treatment decreased the
      abundance of Lactobacillaceae, and increased the abundance of Clostridiaceae in
      both ileal and colonic lumen, which suggests that proanthocyanidins treatment
      changed the bacterial composition and distribution. Administration of
      proanthocyanidins increased the concentration of propionic acid and butyric acid
      in the ileum and colon, which may activate the expression of GPR41. In addition,
      dietary proanthocyanidins improved the antioxidant indices in serum and
      intestinal mucosa, accompanied with increasing expression of barrier occludin.
      Our findings indicated that proanthocyanidins with half-dose colistin was
      equivalent to the antibiotic treatment and assisted weaned animals in resisting
      intestinal oxidative stress by increasing diversity and improving balance of gut
      microbes.

PMID- 27880935
TI  - Evolutionary biologic changes of gut microbiota in an 'adenoma-carcinoma
      sequence' mouse colorectal cancer model induced by 1, 2-Dimethylhydrazine.
AB  - The molecular biological mechanisms underlying the evolutionary biologic changes
      leading to carcinogenesis remain unclear. The main objective of our study was to
      explore the evolution of the microbiota community and molecules related with CRC
      in the dynamic transition from normal colon epithelium to premalignant adenoma
      with the aid of an 'adenoma-carcinoma sequence' mouse CRC model induced by DMH.
      We generated a modified mouse CRC model induced by DMH for DNA sequences, and
      characterized the molecular networks. Data from 454 pyrosequencing of the V3- V5
      region of the 16S rDNA gene and immunohistochemical detection of APC, P53, K-RAS
      and BRAF genes were assessed with Principal coordinates, UniFrac, and Kruskal
      Wallis rank sum test. The inflammatory group showed enrichment of Bacteroidetes
      and Porphyromonadaceae (P < 0.01). OTUs affiliated with Firmicutes were enriched
      in the hyperproliferative group (P < 0.01). Rikenellaceae and Ruminococcaceae
      showed an increasing trend during the CRC process while the opposite pattern was
      observed for Prevotellaceaeand Enterobacteriaceae. OTUs related to Alistipes
      finegoldii were significantly increased during CRC development, P53, K-RAS and
      BRAF, were gradually increased (P < 0.05). Conversely, expression of APC was
      decreased during the course of development of CRC. Our results demonstrate that
      the biological evolutionary shift of gut microbiota, characterized by a gradual
      decrease in 'driver' bacteria and an increase in DNA damage-causing bacteria, is
      accompanied by tumor development in the CRC model. The synergistic actions of
      microbiota dysbiosis and effects of bacterial metabolites on related molecular
      events are proposed to contribute to the progression of CRC tumorigenesis.

PMID- 27880938
TI  - Pathologic stratification of operable lung adenocarcinoma using radiomics
      features extracted from dual energy CT images.
AB  - PURPOSE: To evaluate the usefulness of surrogate biomarkers as predictors of
      histopathologic tumor grade and aggressiveness using radiomics data from dual
      energy computed tomography (DECT), with the ultimate goal of accomplishing
      stratification of early-stage lung adenocarcinoma for optimal treatment. RESULTS:
      Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic
      regression analysis revealed i-uniformity and 97.5th percentile CT attenuation
      value as independent significant factors to stratify grade 2 or 3 from grade 1.
      The AUC value calculated from leave-one-out cross-validation procedure for
      discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514-1), 0.8610 (95% CI:
      0.7547-0.9672), and 0.8394 (95% CI: 0.7045-0.9743), respectively. MATERIALS AND
      METHODS: A total of 80 patients with 91 clinically and radiologically suspected
      stage I or II lung adenocarcinoma were prospectively enrolled. All patients
      underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography
      (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics
      were evaluated using a radiomics approach. Significant features for a tumor
      aggressiveness prediction model were extracted and used to calculate diagnostic
      performance for predicting all pathologic grades. CONCLUSIONS: Quantitative
      radiomics values from DECT imaging metrics can help predict pathologic
      aggressiveness of lung adenocarcinoma.

PMID- 27880937
TI  - Prognostic relevance of miRNA-155 methylation in anaplastic glioma.
AB  - The outcome of patients with anaplastic gliomas varies considerably depending on
      single molecular markers, such as mutations of the isocitrate dehydrogenase (IDH)
      genes, as well as molecular classifications based on epigenetic or genetic
      profiles. Remarkably, 98% of the RNA within a cell is not translated into
      proteins. Of those, especially microRNAs (miRNAs) have been shown not only to
      have a major influence on physiologic processes but also to be deregulated and
      prognostic in malignancies.To find novel survival markers and treatment options
      we performed unbiased DNA methylation screens that revealed 12 putative miRNA
      promoter regions with differential DNA methylation in anaplastic gliomas.
      Methylation of these candidate regions was validated in different independent
      patient cohorts revealing a set of miRNA promoter regions with prognostic
      relevance across data sets. Of those, miR-155 promoter methylation and miR-155
      expression were negatively correlated and especially the methylation showed
      superior correlation with patient survival compared to established
      biomarkers.Functional examinations in malignant glioma cells further cemented the
      relevance of miR-155 for tumor cell viability with transient and stable
      modifications indicating an onco-miRNA activity. MiR-155 also conferred
      resistance towards alkylating temozolomide and radiotherapy as consequence of
      nuclear factor (NF)kappaB activation.Preconditioning glioma cells with an
      NFkappaB inhibitor reduced therapy resistance of miR-155 overexpressing cells.
      These cells resembled tumors with a low methylation of the miR-155 promoter and
      thus mir-155 or NFkappaB inhibition may provide treatment options with a special
      focus on patients with IDH wild type tumors.

PMID- 27880940
TI  - EZH2 overexpression is associated with poor prognosis in patients with glioma.
AB  - Previous studies have investigated the prognostic value of enhancer of zeste
      homolog 2 (EZH2) expression in patients with glioma but conclude contradictory
      results. We aimed to comprehensively evaluate the prognostic role of EZH2 in
      glioma by meta-analysis. The databases of PubMed, Embase and Web of Science were
      searched. Hazard ratio (HR) and 95% confidence interval (CI) were combined to
      assess the association between EZH2 and overall survival (OS) as well as
      progression-free survival (PFS). Odd ratio (OR) and 95% CI were calculated to
      investigate the relevance of EZH2 on clinical factors. Six studies with 575
      patients were included for meta-analysis. The results showed that EZH2
      overexpression was correlated with poor OS (n = 6, HR = 2.23, 95% CI: 1.56-3.19,
      p < 0.001) and PFS (n = 3, HR = 2.23, 95% CI: 1.56-3.19, p < 0.001). Subgroup
      analysis showed that EZH2 had enhanced prognostic value in Asian patients, for
      WHO grade I-IV and when using immunohistochemistry (IHC) method. In addition,
      EZH2 was associated with KPS score < 80. No evidence of publication bias was
      found in this meta-analysis. In conclusion, the present study showed that EZH2
      was a potential prognostic marker for poor OS, PFS and lower KPS score in glioma
      patients.

PMID- 27880941
TI  - Upregulation of microRNA-524-5p enhances the cisplatin sensitivity of gastric
      cancer cells by modulating proliferation and metastasis via targeting SOX9.
AB  - Cisplatin-based chemotherapy is the most commonly used treatment regimen for
      gastric cancer (GC), however, the resistance to cisplatin represents the key
      limitation for the therapeutic efficacy. Aberrant expression of MiR-524-5p
      appears to be involves in tumorigenesis and chemoresistance. However, the
      mechanism by which miR-524-5p mediates effects of cisplatin treatment in GC
      remains poorly understood. Expressions of MiR-524-5p was detected in GC tissues
      and cell lines by qRT-PCR. Cell proliferation was observed by MTT assay; Cell
      migration was detected by transwell migration and invasion assay. The targeting
      protein of miR-524-5p was identified by luciferase reporter assay and western
      blot. We found that downregulation of miR-524-5p in GC tissues and cell lines. SC
      M1 and AZ521 cells resistant to cisplatin expressed low levels of miR-524-5p in
      comparison to the sensitive parental cells. Overexpression of miR-524-5p
      expression in SC-M1 and AZ521 cells inhibited cell proliferation, migration, and
      invasion, and conferred sensitivity to cisplatin-resistant GC cells.
      Subsequently, we identified SOX9 as a functional target protein of miR-524-5p and
      found that SOX9 overexpression could counteracts the chemosensitizing effects of
      miR-524-5p. These results provide novel insight into the regulation of GC
      tumorigenesis and progression by miRNAs. Restoration of miR-524-5p may have
      therapeutic potential against GC.

PMID- 27880939
TI  - Inhibition of the transcriptional repressor complex Bcl-6/BCoR induces
      endothelial sprouting but does not promote tumor growth.
AB  - The oncogenic potential of the transcriptional repressor Bcl-6 (B-cell lymphoma
      6) was originally discovered in non-Hodgkin patients and the soluble Bcl-6
      inhibitor 79-6 was developed to treat diffuse large B-cell lymphomas with
      aberrant Bcl-6 expression. Since we found Bcl-6 and its co-repressor BCoR (Bcl-6
      interacting co-repressor) to be regulated in human microvascular endothelium by
      colorectal cancer cells, we investigated their function in sprouting angiogenesis
      which is central to tumor growth. Based on Bcl-6/BCoR gene silencing we found
      that the transcriptional repressor complex in fact constitutes an endogenous
      inhibitor of vascular sprouting by supporting the stalk cell phenotype: control
      of Notch target genes (HES1, HEY1, DLL4) and cell cycle regulators (cyclin A and
      B1). Thus, when endothelial cells were transiently transfected with Bcl-6 and/or
      BCoR siRNA, vascular sprouting was prominently induced. Comparably, when the
      soluble Bcl-6 inhibitor 79-6 was applied in the mouse retina model of
      physiological angiogenesis, endothelial sprouting and branching were
      significantly enhanced. To address the question whether clinical treatment with
      79-6 might therefore have detrimental therapeutic effects by promoting tumor
      angiogenesis, mouse xenograft models of colorectal cancer and diffuse large B
      cell lymphoma were tested. Despite a tendency to increased tumor vessel density,
      79-6 therapy did not enhance tumor expansion. In contrast, growth of colorectal
      carcinomas was significantly reduced which is likely due to a combined 79-6
      effect on cancer cells and tumor stroma. These findings may provide valuable
      information regarding the future clinical development of Bcl-6 inhibitors.

PMID- 27880944
TI  - Opportunistic Salpingectomy Does Not Affect Ovarian Reserve or Surgical Outcomes
      in Patients Undergoing Laparoscopic Myomectomy.
AB  - OBJECTIVE: To determine whether opportunistic salpingectomy in patients
      undergoing laparoscopic myomectomy has any deleterious effects on ovarian reserve
      and surgical risk. STUDY DESIGN: We performed a retrospective review of patients
      who had no desire for future child bearing and who were undergoing laparoscopic
      myomectomy for symptomatic myomas at 4 institutions. Among them, 41 patients
      concurrently underwent opportunistic salpingectomy (the opportunistic
      salpingectomy group) and 65 patients did not undergo salpingectomy at the time of
      laparoscopic myomectomy (the no-salpingectomy group). The primary and secondary
      outcome measures were change of ovarian reserve determined by the rate of decline
      in the anti-Mullerian hormone (AMH) level from before surgery to 3 months post
      surgery, and surgical outcomes. RESULTS: Baseline characteristics were similar
      between groups. There were also no differences in surgical outcomes, such as
      operative time, operative bleeding, hospital stay, or complications between
      groups. The decline rate in AMH was 18.6% (interquartile range (IQR) 2.6-46.8%)
      in the opportunistic salpingectomy group and 10.4% (IQR 2.6-46.8%) in the no
      salpingectomy group, with no significant difference between groups (p = 0.593).
      CONCLUSION: Opportunistic salpingectomy at the time of laparoscopic myomectomy
      was not associated with negative effects on ovarian reserve or increased surgical
      risk.

PMID- 27880943
TI  - TP53 mutations, expression and interaction networks in human cancers.
AB  - Although the associations of p53 dysfunction, p53 interaction networks and
      oncogenesis have been widely explored, a systematic analysis of TP53 mutations
      and its related interaction networks in various types of human cancers is
      lacking. Our study explored the associations of TP53 mutations, gene expression,
      clinical outcomes, and TP53 interaction networks across 33 cancer types using
      data from The Cancer Genome Atlas (TCGA). We show that TP53 is the most
      frequently mutated gene in a number of cancers, and its mutations appear to be
      early events in cancer initiation. We identified genes potentially repressed by
      p53, and genes whose expression correlates significantly with TP53 expression.
      These gene products may be especially important nodes in p53 interaction networks
      in human cancers. This study shows that while TP53-truncating mutations often
      result in decreased TP53 expression, other non-truncating TP53 mutations result
      in increased TP53 expression in some cancers. Survival analyses in a number of
      cancers show that patients with TP53 mutations are more likely to have worse
      prognoses than TP53-wildtype patients, and that elevated TP53 expression often
      leads to poor clinical outcomes. We identified a set of candidate synthetic
      lethal (SL) genes for TP53, and validated some of these SL interactions using
      data from the Cancer Cell Line Project. These predicted SL genes are promising
      candidates for experimental validation and the development of personalized
      therapeutics for patients with TP53-mutated cancers.

PMID- 27880942
TI  - Acquired resistance to BRAF inhibition induces epithelial-to-mesenchymal
      transition in BRAF (V600E) mutant thyroid cancer by c-Met-mediated AKT
      activation.
AB  - Previously, the authors have identified that c-Met mediates reactivation of the
      PI3K/AKT pathway following BRAF inhibitor treatment in BRAF (V600E) mutant
      anaplastic thyroid cancer, thereby contributing to the acquired drug resistance.
      Therefore dual inhibition of BRAF and c-Met led to sustained treatment response,
      thereby maximizing the specific anti-tumor effect of targeted therapy. The
      present study goes one step further and aims to investigate the effect of
      acquired resistance of BRAF inhibitor on epithelial-to-mesenchymal transition
      (EMT) in BRAF mutant thyroid cancer cells and the effect of dual inhibition from
      combinatorial therapy. Two thyroid cancer cell lines, 8505C and BCPAP were
      selected and treated with BRAF inhibitor, PLX4032 and its effect on EMT were
      examined and compared. Further investigation was carried out in orthotopic
      xenograft mouse models. Unlike BCPAP cells, the BRAF inhibitor resistant 8505C
      cells showed increased expressions of EMT related markers such as vimentin, beta
      catenin, and CD44. The combinatorial treatment of PLX4032 and PHA665752, a c-Met
      inhibitor reversed EMT. Similar results were confirmed in vivo. c-Met-mediated
      reactivation of the PI3K/AKT pathway contributes to the drug resistance to
      PLX4032 in BRAF (V600E) mutant anaplastic thyroid cancer cells and further
      promotes tumor cell migration and invasion by upregulated EMT mechanism. Dual
      inhibition of BRAF and c-Met leads to reversal of EMT, suggesting a maximal
      therapeutic response.

PMID- 27880946
TI  - 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A
      Randomized Trial.
AB  - BACKGROUND: Vitamin D analogs and calcimimetics are used to manage secondary
      hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D
      analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic
      women, and hemodialysis patients. The safety and effectiveness of DP001
      suppressing PTH in dialysis patients previously managed with active vitamin D
      with or without a calcimimetic are presented. METHODS: A multicenter, randomized,
      double-blind study compared DP001 to placebo in hemodialysis patients with serum
      intact PTH (iPTH) >=300 pg/ml. The primary efficacy endpoint was the proportion
      of patients achieving 2 consecutive >=30% decreases in iPTH levels during the 12
      weeks of treatment. Calcium, phosphorus, calcium * phosphorus product and safety
      were also evaluated. The responses to DP001 were compared in patients previously
      treated with both active vitamin D and a calcimimetic to those previously on
      active vitamin D alone. RESULTS: Sixty-two patients were randomized (n = 34
      DP001; n = 28 placebo). At week 12, 78% of all DP001-treated patients and 7% of
      all placebo-treated patients achieved the primary endpoint (p < 0.0001); iPTH
      fell 45% in the DP001 group and increased 37% in the placebo group. No patient
      exceeded the safety threshold of 2 consecutively corrected serum calcium levels
      >=11.0 mg/dl. Patients previously on cinacalcet plus active vitamin D also
      responded to DP001 (n = 10) resulting in a 55% decrease in iPTH, while those on
      placebo (n = 9) increased by 70%. CONCLUSION: DP001 safely and effectively
      suppressed iPTH in hemodialysis patients with SHPT that were previously managed
      with active vitamin D alone or with a calcimimetic (www.clinicaltrials.gov,
      NCT01922843).

PMID- 27880945
TI  - Immunohistochemical Staining of Histological Fragments Derived from Salivary
      Gland Tumour Fine-Needle Biopsy Aspirates.
AB  - OBJECTIVES: The aim of this study was to describe a method for analysing
      histological fragments derived from fine- needle aspirate biopsy (FNAB) of
      salivary gland tumours (SGTs), and to evaluate the use of immunohistochemistry
      (IHC) on them. STUDY DESIGN: We reviewed all 509 FNAB pathology reports taken
      from SGTs at Helsinki University Hospital, Finland, between 1999 and 2009. In 51%
      of the cases (n = 209) "histo-fragments" had been obtained and 31 had been
      further analysed by IHC. Of these, 25 (81%) were available for review. We
      evaluated the benefit of IHC by relating its added value to the preoperative
      cytological diagnosis and its accuracy compared with the postoperative
      histological diagnosis. RESULTS: Most of the samples analysed by IHC were
      assigned a malignant diagnosis, with 12 different types of malignancy
      represented. IHC was advantageous in 76% of the cases. In the 108 studies using
      IHC in this series, antibodies to 36 different antigens were used. CONCLUSION:
      Analysis of histo-fragments in FNABs using IHC can be valuable in specific
      differential diagnostics and raises diagnostic accuracy in SGTs.

PMID- 27880949
TI  - Ecological and Behavioural Factors Influencing Territorial Call Rates for the
      Bolivian Titi Monkeys, Plecturocebus modestus and Plecturocebus olallae.
AB  - Primate territorial calls have been used to locate groups in censuses. Daily
      variations in call rates are a potential source of error in these studies. To
      obtain more accurate estimations of population density it is necessary to
      determine how much variation there is in group call rates and to identify the
      factors that influence them. We present data on the emission of territorial calls
      by two threatened and endemic titi monkeys in Bolivia: Plecturocebus olallae and
      P. modestus. We found interspecific differences in daily call rates (52% P.
      modestus and 33% P. olallae). Groups inhabiting more continuous forests vocalized
      more frequently than groups in fragmented forests, which might be linked to the
      higher abundance of groups in less fragmented forests. We found seasonal
      differences in call rates between species, with more frequent calling in P.
      modestus during the dry season, while P. olallae called more frequently in the
      rainy season. The study groups emitted territorial calls mostly from the central
      zones of their territories, suggesting they do not face intense spatial
      competition with neighbouring groups. Our results improve the general ecological
      knowledge on P. olallae and P. modestus, and can also be used to improve
      population abundance studies and ongoing conservation efforts.

PMID- 27880953
TI  - Deletion of TOP3B Is Associated with Cognitive Impairment and Facial Dysmorphism.
AB  - Deletions of different regions of chromosome 22q11 have been extensively
      characterized in the literature, with a recent review outlining common deletions
      with a standardized system proposed for classification and nomenclature. The
      genotype-phenotype relationships have not been sufficiently elucidated for these
      deletions, and it remains unclear which specific genes play the dominant roles in
      producing associated clinical features. Several deletions involve entirely
      distinct regions of chromosome 22q11 but do not overlap, suggesting that a number
      of different genes contribute to the clinical features. Studies of patients with
      small deletions involving only 1 or 2 genes may provide more convincing evidence
      for the impact of individual genes on the observed phenotype. In this case
      report, we present a 12-year-old female with autism, cognitive impairment,
      dysmorphic features, and behavioral concerns and a 268-kb deletion of chromosome
      22q11.22 including TOP3B, the only recognized disease-causing gene in the
      deletion. The mechanism of pathogenesis contributing significantly to our
      patient's clinical findings may relate to interaction between TOP3B and fragile X
      mental retardation protein (FMRP), an mRNA-binding protein that regulates
      translation and is altered in fragile X syndrome, a condition involving
      developmental delay, learning disability, and autism. All these features are
      recognized in our patient.

PMID- 27880954
TI  - The Protective Effect of Brown-, Gray-, and Blue-Tinted Lenses against Blue LED
      Light-Induced Cell Death in A2E-Laden Human Retinal Pigment Epithelial Cells.
AB  - A2E-laden ARPE-19 cells were exposed to a blue light to induce cytotoxicity, in
      order to investigate the protective effects of various tinted ophthalmic lenses
      against photo-induced cytotoxicity in human retinal pigment epithelial (RPE)
      cells laden with A2E, known to be among the etiologies of age-related macular
      degeneration (AMD). Different-colored tinted lenses with varying levels of tint
      and different filtering characteristics, such as polarized, blue-cut, and
      photochromatic lenses, were placed over the cells, and the protective efficacies
      thereof were evaluated by lactate dehydrogenase assay. When tinted lenses were
      placed over ARPE-19 cells, there were different reductions in cytotoxicity
      according to the colors and tint levels. The level of protection afforded by
      brown-tinted lenses was 6.9, 36.1, and 49% with a tint level of 15, 50, and 80%,
      respectively. For gray-tinted lenses, the protective effect was 16.3, 35, and
      43.4% for the corresponding degree of tint, respectively. In the case of blue
      tinted lenses, a protective effect of 20% was observed with 80% tinted lenses,
      but 15 and 50% tinted lenses provided no significant protection. In addition,
      photochromic lenses showed a protective effect but blue-cut lenses and polarized
      lenses provided no significant protection. Tinted lenses significantly reduced
      cytotoxicity in RPE cells irradiated with blue light. The protection was more
      efficient in lenses with a brown or gray tint than in blue-tinted lenses. Tinted
      glasses may provide significant protection against potential blue-light-induced
      photochemical and photo-oxidative damage in RPE cells.

PMID- 27880950
TI  - Protease-Activated Receptor 1 Contributes to Angiotensin II-Induced
      Cardiovascular Remodeling and Inflammation.
AB  - BACKGROUND: Angiotensin II (Ang II) plays an important role in cardiovascular
      disease. It also leads to the activation of coagulation. The coagulation protease
      thrombin induces cellular responses by activating protease-activated receptor 1
      (PAR-1). We investigated whether PAR-1 contributes to Ang II-induced
      cardiovascular remodeling and inflammation. METHODS AND RESULTS: PAR-1+/+ (wild
      type; WT) and PAR-1-/- mice were infused with Ang II (600 ng/kg/min) for up to 4
      weeks. In WT mice, this dose of Ang II did not cause a significant increase in
      blood pressure but it did cause pathological changes in both the aorta and the
      heart. Ang II infusion resulted in vascular remodeling of the aorta, demonstrated
      by a significant increase in medial wall thickening and perivascular fibrosis.
      Importantly, both parameters were significantly attenuated by PAR-1 deficiency.
      Furthermore, perivascular fibrosis around coronary vessels was reduced in Ang II
      treated PAR-1-/- mice compared to WT mice. In addition, PAR-1 deficiency
      significantly attenuated Ang II induction of inflammatory cytokines and
      profibrotic genes in the aortas compared to WT mice. Finally, PAR-1 deficiency
      had no effect on Ang II-induced heart hypertrophy. However, the heart function
      measured by fractional shortening was less impaired in PAR-1-/- mice than in WT
      mice. CONCLUSION: Our data indicate that PAR-1 plays a significant role in
      cardiovascular remodeling mediated by a blood pressure-independent action of Ang
      II.

PMID- 27880956
TI  - Contents Vol. 85, 2016.

PMID- 27880955
TI  - Long-Term Angiotensin II Receptor Blockade Limits Hypertension, Aortic
      Dysfunction, and Structural Remodeling in a Rat Model of Chronic Kidney Disease.
AB  - BACKGROUND/AIMS: Chronic kidney disease (CKD) is associated with large artery
      remodeling, endothelial dysfunction and calcification, with angiotensin II (Ang
      II) a known driver of these pathologies. We investigated long-term Ang II type 1
      receptor inhibition with valsartan on aortic function and structure in the Lewis
      polycystic kidney (LPK) rat model of CKD. METHODS: Mixed sex LPK and Lewis
      control (total n = 28) treated (valsartan 60 mg/kg/day p.o. from 4 to 18 weeks)
      and vehicle groups were studied. Functional responses to noradrenaline (NA),
      potassium chloride and endothelium-dependent and independent relaxations were
      investigated in vitro using acetylcholine hydrochloride (ACh) and sodium
      nitroprusside (SNP), respectively. Effects of the nitric oxide synthase (NOS)
      substrate L-arginine, NOS inhibitor L-NAME and cyclooxygenase inhibitor
      indomethacin on ACh responses were examined. RESULTS: In the LPK, valsartan
      reduced systolic blood pressure and urinary protein, ameliorated exaggerated
      sensitivity to NA, and normalized endothelium-dependent (ACh-Rmax; 91 +/- 7 vs.
      59 +/- 6%, p = 0.0001) and independent dysfunction (SNP-Rmax; 99 +/- 1 vs. 82 +/-
      7%, p = 0.040), as well as improving NO-dependent relaxation (Rmax; -51 +/- 6 vs.
      -26 +/- 9%, p = 0.008). Valsartan also reduced aortic wall hypertrophy, elastin
      disruption/fragmentation, calcification, media cystic degeneration, and levels of
      matrix metalloproteinase 9. CONCLUSIONS: This study highlights the role of Ang II
      in driving vascular manifestations of CKD and indicates that early treatment can
      significantly limit pathological changes.

PMID- 27880958
TI  - Factors Influencing Repair Outcomes of Vesicovaginal Fistula: A Retrospective
      Review of 139 Procedures.
AB  - INTRODUCTION: We aimed to report the outcomes of patients undergoing
      vesicovaginal fistula (VVF) repair to identify prognostic factors. MATERIALS AND
      METHODS: Patients who underwent VVF repair between January 2009 and October 2015
      were reviewed. Primary outcome was fistula closure at 3 months. RESULTS: A total
      of 123 patients and 139 procedures of VVF repair were reviewed. The overall
      success rate was 85.6%. There were no significant differences in age (p = 0.476),
      etiology (p = 0.900), fistula duration (p = 0.491) and number of repairs (p =
      0.509) between success and fail group. Moderate or severe perifistula fibrosis
      and multiple fistula were associated with failure in repair of fistula (70.8 vs.
      93.4%, p < 0.001; 62.5 vs. 88.6%, p = 0.005). No difference was seen in success
      rate of vaginal and abdominal approaches (86.0 vs. 85.0%, p = 0.800). Logistic
      regression analysis identified fistula number (p = 0.003) and perifistula
      fibrosis (p = 0.002) as 2 independent prognostic factors. Medium/large fistulas
      were 3.2 times more likely to fail in repair than small fistulas (OR 3.2, 95% CI
      0.95-10.6, p = 0.061). CONCLUSIONS: Fistula number and perifistula fibrosis were
      2 independent prognostic factors for fistula repair. Unsuccessful closure was
      more likely in medium/large VVF.

PMID- 27880957
TI  - Integrated Use of Lung Ultrasound and Chest X-Ray in the Detection of
      Interstitial Lung Disease.
AB  - BACKGROUND: Current data have shown that lung ultrasound (LUS) may be useful in
      the detection of interstitial lung disease (ILD) by the evaluation of B-lines,
      the sonographic marker of pulmonary interstitial syndrome. Nevertheless, no
      prospective study has compared LUS to chest X-ray (CXR) for ILD assessment, and
      there is no general agreement on the specific echographic diagnostic criteria for
      defining ILD. OBJECTIVES: The aims of this study were (1) to compare the accuracy
      of LUS and CXR in the detection of ILD using high-resolution CT (HRCT) as the
      gold standard and (2) to compare the accuracy of different echographic diagnostic
      criteria for ILD diagnosis. METHODS: LUS was performed on 104 patients undergoing
      HRCT for suspected ILD. In 49 patients, a CXR scan performed within 3 months of
      HRCT was analyzed. ILD was defined as the presence of >=5 B-lines in >=3 chest
      areas. A total B-line score (TBLS) was also calculated, as in previous studies.
      The observers evaluating LUS and CXR were blinded to the HRCT results and
      clinical data. RESULTS: On HRCT, ILD was assessed in 50 patients. CXR was
      specific (91%; 95% CI 80-100) but not sensitive (48%; 95% CI 28-67). Conversely,
      LUS showed high sensitivity (92%; 95% CI 84-99) and low specificity (79%; 95% CI
      69-90). Using a TBLS, sensitivity did not change, while specificity decreased.
      CONCLUSIONS: LUS could be a sensitive tool for ILD detection. CXR and LUS have
      different but complementary features, and their combined use could reduce the
      need for HRCT. The use of different diagnostic criteria for defining ILD does not
      affect sensitivity but influences specificity.

PMID- 27880959
TI  - Morphology and Ciliary Motion of the Middle Ear Mucosa of Neonatal and Adult
      Gerbils.
AB  - BACKGROUND/AIMS: Since the middle ear cavity plays an important role in middle
      ear effusion, the goal of this study is to examine the morphological and
      functional development of the middle ear mucosa in neonatal and adult gerbils.
      METHODS: Gerbils aged between postnatal day 1 (P1) and P26 were used for the
      experiments. The morphological development of the middle ear cavity was measured
      by using the celloidin embedding method and scanning electronic microscope.
      Ciliary motion was determined and calibrated by a photodiode-based measurement
      system. RESULTS: The area of the middle ear increased significantly from 0.42 +/-
      0.02 mm2 (n = 8) at P1 to 2.6 +/- 0.03 mm2 (n = 8) at P26. At P1, all regions
      were covered by densely populated ciliated cells. A significant reduction of the
      density of ciliated cells was found between P8 and P18 (p < 0.05). The beat
      frequency at P1 is not statistically different from that of P8 (p > 0.05).
      However, the beat frequency increased significantly between P8 and P18 (p <
      0.05). CONCLUSION: Middle ear mucosa underwent a significant change between P1
      and P18. The cilia morphology and function (ciliary motion) are fully mature at
      P18. This may explain the high incidence of middle ear effusion in the neonatal
      period in humans.

PMID- 27880960
TI  - Antifouling Activity towards Mussel by Small-Molecule Compounds from a Strain of
      Vibrio alginolyticus Bacterium Associated with Sea Anemone Haliplanella sp.
AB  - Mussels are major fouling organisms causing serious technical and economic
      problems. In this study, antifouling activity towards mussel was found in three
      compounds isolated from a marine bacterium associated with the sea anemone
      Haliplanella sp. This bacterial strain, called PE2, was identified as Vibrio
      alginolyticus using morphology, biochemical tests, and phylogenetic analysis
      based on sequences of 16S rRNA and four housekeeping genes (rpoD, gyrB, rctB, and
      toxR). Three small-molecule compounds (indole, 3-formylindole, and cyclo (Pro
      Leu)) were purified from the ethyl acetate extract of V. alginolyticus PE2 using
      column chromatography techniques. They all significantly inhibited byssal thread
      production of the green mussel Perna viridis, with EC50 values of 24.45 MUg/ml
      for indole, 50.07 MUg/ml for 3-formylindole, and 49.24 MUg/ml for cyclo (Pro
      Leu). Previous research on the antifouling activity of metabolites from marine
      bacteria towards mussels is scarce. Indole, 3-formylindole and cyclo (Pro-Leu)
      also exhibited antifouling activity against settlement of the barnacle Balanus
      albicostatus (EC50 values of 8.84, 0.43, and 11.35 MUg/ml, respectively) and the
      marine bacterium Pseudomonas sp. (EC50 values of 42.68, 69.68, and 39.05 MUg/ml,
      respectively). These results suggested that the three compounds are potentially
      useful for environmentally friendly mussel control and/or the development of new
      antifouling additives that are effective against several biofoulers.

PMID- 27880961
TI  - Characterization of Aspergillus sojae Isolated from Meju, Korean Traditional
      Fermented Soybean Brick.
AB  - Initially, we screened 18 Aspergillus sojae-like strains from Aspergillus spp.
      isolated from meju (Korean traditional fermented soybean brick) according to
      their morphological characteristics. Because members of Aspergillus section Flavi
      are often incorrectly identified because of their phylogenetic similarity, we re
      identified these strains at the morphological and molecular genetic levels.
      Fourteen strains were finally identified as A. sojae. The isolates produced
      protease and alpha-amylase with ranges of 2.66-10.64 and 21.53-106.73 unit/g
      initial dry substrate (U/g-IDS), respectively, which were equivalent to those of
      the koji (starter mold) strains employed to produce Japanese soy sauce. Among the
      isolates and Japanese koji strains, strains SMF 127 and SMF 131 had the highest
      leucine aminopeptidase (LAP) activities at 6.00 and 6.06 U/g-IDS, respectively.
      LAP plays an important role in flavor development because of the production of
      low-molecular-weight peptides that affect the taste and decrease bitterness. SMF
      127 and SMF 131 appeared to be non-aflatoxigenic because of a termination point
      mutation in aflR and the lack of the polyketide synthase gene found in other A.
      sojae strains. In addition, SMF 127 and SMF 131 were not cyclopiazonic acid (CPA)
      producers because of the deletion of maoA, dmaT, and pks/nrps, which are involved
      in CPA biosynthesis. Therefore, A. sojae strains such as SMF 127 and SMF 131,
      which have high protease and LAP activities and are free of safety issues, can be
      considered good starters for soybean fermentations, such as in the production of
      the Korean fermented soybean products meju, doenjang, and ganjang.

PMID- 27880963
TI  - Enhanced Production of Gamma-Aminobutyric Acid by Optimizing Culture Conditions
      of Lactobacillus brevis HYE1 Isolated from Kimchi, a Korean Fermented Food.
AB  - This study evaluated the effects of culture conditions, including carbon and
      nitrogen sources, L-monosodium glutamate (MSG), and initial pH, on gamma
      aminobutyric acid (GABA) production by Lactobacillus brevis HYE1 isolated from
      kimchi, a Korean traditional fermented food. L. brevis HYE1 was screened by the
      production analysis of GABA and genetic analysis of the glutamate decarboxylase
      gene, resulting in 14.64 mM GABA after 48 h of cultivation in MRS medium
      containing 1% (w/v) MSG. In order to increase GABA production by L. brevis HYE1,
      the effects of carbon and nitrogen sources on GABA production were preliminarily
      investigated via one-factor-at-a-time optimization strategy. As the results, 2%
      maltose and 3% tryptone were determined to produce 17.93 mM GABA in modified MRS
      medium with 1% (w/v) MSG. In addition, the optimal MSG concentration and initial
      pH were determined to be 1% and 5.0, respectively, resulting in production of
      18.97 mM GABA. Thereafter, response surface methodology (RSM) was applied to
      determine the optimal conditions of the above four factors. The results indicate
      that pH was the most significant factor for GABA production. The optimal culture
      conditions for maximum GABA production were also determined to be 2.14% (w/v)
      maltose, 4.01% (w/v) tryptone, 2.38% (w/v) MSG, and an initial pH of 4.74. In
      these conditions, GABA production by L. brevis HYE1 was predicted to be 21.44 mM
      using the RSM model. The experiment was performed under these optimized
      conditions, resulting in GABA production of 18.76 mM. These results show that the
      predicted and experimental values of GABA production are in good agreement.

PMID- 27880962
TI  - Production of Cellulases by Rhizopus stolonifer from Glucose-Containing Media
      Based on the Regulation of Transcriptional Regulator CRE.
AB  - Carbon catabolite repression is a crucial regulation mechanism in microorganisms,
      but its characteristic in Rhizopus is still unclear. We extracted a carbon
      regulation gene, cre, that encoded a carbon catabolite repressor protein (CRE)
      from Rhizopus stolonifer TP-02, and studied the regulation of CRE by real-time
      qPCR. CRE responded to glucose in a certain range, where it could significantly
      regulate part of the cellulase genes (eg, bg, and cbh2) without cbh1. In the
      comparison of the response of cre and four cellulase genes to
      carboxymethylcellulose sodium and a simple carbon source (lactose), the effect of
      CRE was only related to the concentration of reducing sugars. By regulating the
      reducing sugars to range from 0.4% to 0.6%, a glucose-containing medium with
      lactose as the inducer could effectively induce cellulases without the repression
      of CRE. This regulation method could potentially reduce the cost of enzymes
      produced in industries and provide a possible solution to achieve the large-scale
      synthesis of cellulases.

PMID- 27880964
TI  - Protective Effects of Standardized Siegesbeckia glabrescens Extract and Its
      Active Compound Kirenol against UVB-Induced Photoaging through Inhibition of
      MAPK/NF-kappaB Pathways.
AB  - Anti-photoaging effects of standardized Siegesbeckia glabrescens extract (SGE)
      and its major active compound kirenol were investigated using Hs68 human dermal
      fibroblasts and hairless mice, respectively. UVB-irradiated hairless mice that
      received oral SGE (600 mg/kg/day) showed reduced wrinkle formation and skinfold
      thickness compared with the UVB-irradiated control. Furthermore, SGE treatment
      increased the mRNA levels of collagen synthesis genes (COL1A1, COL3A1, COL4A1,
      and COL7A1) and activated antioxidant enzyme (catalase), while suppressing matrix
      metalloproteinase (MMP-2, -3, -9, and -13) expression. In Hs68 fibroblasts,
      kirenol also significantly suppressed MMP expression while increasing the
      expression of COL1A1, COL3A1, and COL7A1. Collectively, our data demonstrate that
      both SGE and kirenol attenuated UVB-induced photoaging in hairless mice and
      fibroblasts through inhibition of the mitogen-activated protein kinases and
      nuclear factor kappa B pathways, suggesting that SGE has potential to serve as a
      natural anti-photoaging nutraceutical.

PMID- 27880965
TI  - [Update in pediatric endoscopy].
AB  - Pediatric endoscopy is a good example of a multidiscipliniary approach. In many,
      but not all hospitals, endoscopy in pediatric patients is performed by
      conventional gastroenterologists and only in some centers by pediatric
      gastroenterologists. This is due to the fact that not as many pediatric
      gastroenterologists are available. Some of the centers are very experienced.
      There is only limited literature on pediatric endoscopy available. Therefore, an
      update may be relevant for both the adult and pediatric gastroenterologists. Here
      we describe current knowledge on endoscopic procedures in pediatric patients.

PMID- 27880966
TI  - Age-Dependency of Location of Epileptic Foci in "Continuous Spike-and-Waves
      during Sleep": A Parallel to the Posterior-Anterior Trajectory of Slow Wave
      Activity.
AB  - BACKGROUND: Epileptic encephalopathy with continuous spike-and-waves during sleep
      (CSWS) occurs during childhood and is characterized by an activation of spike
      wave complexes during slow wave sleep. The location of epileptic foci is
      variable, as is etiology. A relationship between the epileptic focus and age has
      been shown in various focal epilepsies following a posterior-anterior trajectory,
      and a link to brain maturation has been proposed. We hypothesize that in CSWS,
      maximal spike wave activity, corresponding to the epileptic focus, is related to
      age and shows a posterior-anterior evolution. FINDINGS: In a retrospective cross
      sectional study on CSWS (22 EEGs of 22 patients aged 3.1-13.5 years), the
      location of the epileptic focus is related to age and follows a posterior
      anterior course. Younger patients are more likely to have posterior foci than
      older ones. CONCLUSIONS: We propose that the posterior-anterior trajectory of
      maximal spike waves in CSWS might reflect maturational changes of maximal
      expression of sleep slow waves, which follow a comparable course. Epileptic spike
      waves, that is, "hyper-synchronized slow waves" may occur at the place where the
      highest and therefore most synchronized slow waves meet brain tissue with an
      increased susceptibility to synchronization.

PMID- 27880967
TI  - Early Prenatal MRI of Cervical "Abortive" Myelocystocele: Case Report and Review
      of the Literature.
AB  - Cervical abortive myelocistocele is a very rare congenital malformation. In this
      case report, we describe the prenatal magnetic resonance imaging (MRI) of such
      entity in a 20-week gestational age fetus, whose imaging features showed to be
      different from the only other previous prenatal report. We underscored the value
      of fetal MR for counseling and prognosis, especially when assessing the integrity
      of the spinal cord.

PMID- 27880968
TI  - Results of a New Treatment Concept for Concomitant Lesion of Medial Collateral
      Ligament in Patients with Rupture of Anterior Cruciate Ligament.
AB  - Anteromedial knee injury with rupture of anterior cruciate ligament (ACL) and
      concomitant lesion of medial collateral ligament (MCL) is common in athletes. No
      standardized treatment concept can be found within the literature. This study
      presents results of a new treatment concept for concomitant MCL lesions in
      patients with ACL rupture. In this study, 67 recreational athletes with ACL
      injury and concomitant MCL lesion were treated according to a distinct treatment
      concept. Patients were classified in six different types of concomitant MCL
      lesion depending on grade of MCL lesion and presence of anteromedial rotatory
      instability (AMRI). Final classification and surgical indication were determined
      6 weeks posttraumatic. All patients received ACL reconstruction. MCL was treated
      by surgical or conservative regime due to type of concomitant MCL lesion.
      International Knee Documentation Committee (IKDC), AMRI, and Lysholm scores were
      evaluated both preoperatively and after 6 weeks, 16 weeks, 12 months, and 18
      months postoperatively. All patients could be uniquely classified and treated
      according to the introduced treatment concept. AMRI was verifiable in patients
      with grade II and III MCL lesions. All patients showed good to excellent clinical
      results at the follow-up examinations. In all 67 patients (100%), the findings
      were graded as normal or nearly normal according to the IKDC knee examination
      form. Lysholm score averaged 93.9 at final follow-up. The introduced treatment
      concept showed good results on short-term outcome and provides a sufficient
      treatment strategy for concomitant MCL lesions in athletes with ACL rupture.

PMID- 27880969
TI  - The Prevalence of Cruciate Ligament and Meniscus Knee Injury in Young Adults and
      Associations with Gender, Body Mass Index, and Height a Large Cross-Sectional
      Study.
AB  - Anterior cruciate ligament and meniscal injuries are associated with secondary
      osteoarthrosis which may lead to functional impairment and economic burden. The
      prevalence of knee injury has not been studied in depth. Our purpose was to
      report the prevalence of knee ligament and meniscal injuries and their
      associations with gender, body mass index (BMI), and height in young adults and
      to characterize individuals with meniscal injuries who gained full recovery. A
      cross-sectional, population-based study was conducted. Information on the
      disability codes of knee ligament and meniscal injury according to the
      Regulations of Medical Fitness Determination was retrieved from a medical
      database containing records of young prerecruits into mandatory service. Logistic
      regression assessed the association between genders, BMI, and body height to knee
      injuries. A total of 825,187 subjects were included. Prevalence of knee injuries
      was 0.35%. Males had 2.2-fold more knee injuries than females. Increased BMI was
      associated with increased prevalence of knee injury in both genders, more
      significantly in females (overweight and obese females had an odds ratio of 1.406
      and 1.519, respectively, to suffer from concomitant meniscal and ligamentous knee
      injury). Being underweight was associated with a lower prevalence of knee injury.
      An above normal BMI was more significantly associated with meniscal and/or
      ligament injuries that did not fully recover (females > males). Body height was
      associated with isolated meniscal injury in both genders. We found an association
      between BMI, body height, and knee injury in both males and females. Higher body
      height and higher BMI might be risk factors for knee injuries. Higher BMI was
      associated with greater probability of disability coding. Meniscal and ligament
      injuries are more common among males.

PMID- 27880970
TI  - Total Knee Arthroplasty: What to Expect? A Survey of the Members of the Dutch
      Knee Society on Long-Term Recovery after Total Knee Arthroplasty.
AB  - The rate of satisfaction after total knee arthroplasty (TKA) is consistently
      reported around 80%, leaving one in five patients unsatisfied to some extent.
      Fulfillment of expectations is reported as the strongest predictor of treatment
      satisfaction. In this study, we aimed to evaluate what Dutch orthopedic surgeons
      assume are realistic expectations for recovery 1 year after TKA. We invited the
      members of the Dutch Knee Society (DKS) to fill out a web-based questionnaire.
      For expectation measurement, the validated Dutch version of the Hospital for
      Special Surgery (HSS) knee replacement expectations survey was used. A total of
      150 invitations were successfully sent; 84 orthopedic surgeons responded (56%).
      The overall HSS knee replacement expectation score was 66.0 (standard deviation,
      14.0) on a 0 to 100 scale. Most improvement was predicted for the items "pain
      relief" and "walking short distances." Expectations related to patients' ability
      to kneel or squat after TKA were scored poorly. To the opinion of the members of
      the DKS, after TKA improvement can be expected in domains of pain, function,
      activities, and psychological wellbeing. Return to normal is not likely to occur,
      especially in demanding physical activities.

PMID- 27880971
TI  - The Risk Factors of Postoperative Delirium after Total Knee Arthroplasty.
AB  - We investigated the results of delirium which developed after total knee
      arthroplasty (TKA) and the risk factors for delirium in the patients who are
      older than 65 years. From March 2008 to March 2012, we performed a retrospective
      study on 296 knees of 265 patients who were treated with TKA. They were divided
      into two groups: 216 patients without delirium and 49 patients diagnosed with
      delirium by psychiatry. We analyzed the risk factors into three categories:
      First, the preoperative factors including gender, age, body mass index (BMI),
      clinical and functional knee joint score (Knee Society Knee Score and Knee
      Society Function Score) and the number of underlying diseases and associations
      with each disease; Second, the operative factors including the anesthesia method,
      amount of blood loss, operating time, laboratory factors, and transfusion count;
      Third, the postoperative factors such as start time of walking and duration of
      hospital stay were analyzed. There were significant statistical difference
      between two groups just in age, history of dementia, cerebrovascular disease,
      difference of hemoglobin and albumin, start time of walking, and duration of
      hospital stay. The delirium after TKA delays the postoperative ambulation and
      extends the hospital stay, which causes functional and socioeconomic loss of
      patients. Therefore, the risk factors for delirium should be assessed and proper
      prevention and management should be conducted.

PMID- 27880972
TI  - Interferons-beta versus glatiramer acetate for relapsing-remitting multiple
      sclerosis.
AB  - BACKGROUND: Interferons-beta (IFNs-beta) and glatiramer acetate (GA) were the
      first two disease-modifying therapies (DMTs) approved 20 years ago for the
      treatment of multiple sclerosis (MS). DMTs' prescription rates as first or
      switching therapies and their costs have both increased substantially over the
      past decade. As more DMTs become available, the choice of a specific DMT should
      reflect the risk/benefit profile, as well as the impact on quality of life. As MS
      cohorts enrolled in different studies can vary significantly, head-to-head trials
      are considered the best approach for gaining objective reliable data when two
      different drugs are compared. The purpose of this systematic review is to
      summarise available evidence on the comparative effectiveness of IFNs-beta and GA
      on disease course through the analysis of head-to-head trials.This is an update
      of the Cochrane review 'Interferons-beta versus glatiramer acetate for relapsing
      remitting multiple sclerosis' (first published in the Cochrane Library 2014,
      Issue 7). OBJECTIVES: To assess whether IFNs-beta and GA differ in terms of
      safety and efficacy in the treatment of people with relapsing-remitting (RR) MS.
      SEARCH METHODS: We searched the Trials Register of the Cochrane Multiple
      Sclerosis and Rare Diseases of the CNS Group (08 August 2016) and the reference
      lists of retrieved articles. We contacted authors and pharmaceutical companies.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing directly IFNs
      beta versus GA in study participants affected by RRMS. DATA COLLECTION AND
      ANALYSIS: We used standard methodological procedures as expected by Cochrane.
      MAIN RESULTS: Six trials were included and five trials contributed to this review
      with data. A total of 2904 participants were randomly assigned to IFNs (1704) and
      GA (1200). The treatment duration was three years for one study, two years for
      the other four RCTs while one study was stopped early (after one year). The IFNs
      analysed in comparison with GA were IFN-beta 1b 250 mcg (two trials, 933
      participants), IFN-beta 1a 44 mcg (three trials, 466 participants) and IFN-beta
      1a 30 mcg (two trials, 305 participants). Enrolled participants were affected by
      active RRMS. All studies were at high risk for attrition bias. Three trials are
      still ongoing, one of them completed.Both therapies showed similar clinical
      efficacy at 24 months, given the primary outcome variables (number of
      participants with relapse (risk ratio (RR) 1.04, 95% confidence interval (CI)
      0.87 to 1.24) or progression (RR 1.11, 95% CI 0.91 to 1.35). However at 36
      months, evidence from a single study suggests that relapse rates were higher in
      the group given IFNs than in the GA group (RR 1.40, 95% CI 1.13 to 1.74, P value
      0.002).Secondary magnetic resonance imaging (MRI) outcomes analysis showed that
      effects on new or enlarging T2- or new contrast-enhancing T1 lesions at 24 months
      were similar (mean difference (MD) -0.15, 95% CI -0.68 to 0.39, and MD -0.14, 95%
      CI -0.30 to 0.02, respectively). However, the reduction in T2- and T1-weighted
      lesion volume was significantly greater in the groups given IFNs than in the GA
      groups (MD -0.58, 95% CI -0.99 to -0.18, P value 0.004, and MD -0.20, 95% CI 
      0.33 to -0.07, P value 0.003, respectively).The number of participants who
      dropped out of the study because of adverse events was similar in the two groups
      (RR 0.95, 95% CI 0.64 to 1.40).The quality of evidence for primary outcomes was
      judged as moderate for clinical end points, but for safety and some MRI outcomes
      (number of active T2 lesions), quality was judged as low. AUTHORS' CONCLUSIONS:
      The effects of IFNs-beta and GA in the treatment of people with RRMS, including
      clinical (e.g. people with relapse, risk to progression) and MRI (Gd-enhancing
      lesions) measures, seem to be similar or to show only small differences. When MRI
      lesion load accrual is considered, the effect of the two treatments differs, in
      that IFNs-beta were found to limit the increase in lesion burden as compared with
      GA. Evidence was insufficient for a comparison of the effects of the two
      treatments on patient-reported outcomes, such as quality-of-life measures.

PMID- 27880973
TI  - Immunopathogenesis of systemic lupus erythematosus and rheumatoid arthritis: the
      role of aberrant expression of non-coding RNAs in T cells.
AB  - Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs
      (lncRNAs), are RNA molecules that do not translate into protein. Both miRNAs and
      lncRNAs are known to regulate gene expression and to play an essential role in T
      cell differentiation and function. Both systemic lupus erythematosus (SLE), a
      prototypic systemic autoimmune disease, and rheumatoid arthritis (RA), a
      representative disease of inflammatory arthritis, are characterized by a complex
      dysfunction in the innate and adaptive immunity. T cells play a central role in
      cell-mediated immune response and multiple defects in T cells from patients with
      SLE and RA have been observed. Abnormality in T cell signalling, cytokine and
      chemokine production, T cell activation and apoptosis, T cell differentiation and
      DNA methylation that are associated closely with the aberrant expression of a
      number of miRNAs and lncRNAs have been implicated in the immunopathogenesis of
      SLE and RA. This review aims to provide an overview of the current state of
      research on the abnormal expression of miRNAs and lncRNAs in T cells and their
      roles in the immunopathogenesis of SLE and RA. In addition, by comparing the
      differences in aberrant expression of miRNAs and lncRNAs in T cells between
      patients with SLE and RA, controversial areas are highlighted that warrant
      further investigation.

PMID- 27880974
TI  - Deep sequencing of the TCR-beta repertoire of human forkhead box protein 3
      (FoxP3)+ and FoxP3- T cells suggests that they are completely distinct and non
      overlapping.
AB  - Maintenance of peripheral tolerance requires a balance between autoreactive
      conventional T cells (Tconv ) and thymically derived forkhead box protein 3
      (FoxP3)+ regulatory T cells (tTregs ). Considerable controversy exists regarding
      the similarities/differences in T cell receptor (TCR) repertoires expressed by
      Tconv and tTregs . We generated highly purified populations of human adult and
      cord blood Tconv and tTregs based on the differential expression of CD25 and
      CD127. The purity of the sorted populations was validated by intracellular
      staining for FoxP3 and Helios. We also purified an overlap group of CD4 T cells
      from adult donors to ensure that considerable numbers of shared clonotypes could
      be detected when present. We used deep sequencing of entire TCR-beta CDR3
      sequences to analyse the TCR repertoire of Tconv and tTregs . Our studies suggest
      that both neonatal and adult human Tconv and tTreg cells are, in fact, entirely
      distinct CD4 T cell lineages.

PMID- 27880975
TI  - RORgammat expression in Tregs promotes systemic lupus erythematosus via IL-17
      secretion, alteration of Treg phenotype and suppression of Th2 responses.
AB  - Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex
      and poorly understood immunopathogenesis. However, a pathogenic role for the T
      helper type 17 (Th17) axis was demonstrated by many studies, while regulatory T
      cells (Tregs ) were shown to mediate protection. Recently, we and others
      characterized a novel and independent T cell population expressing both the Treg
      characteristic transcription factor forkhead box protein 3 (FoxP3) and the Th17
      defining retinoic acid receptor-related orphan nuclear receptor gammat
      (RORgammat). Studies in a model of acute glomerulonephritis unveiled potent
      regulatory, but also proinflammatory, functions of RORgammat+ FoxP3+ Tregs . This
      bi-functional nature prompted us to suggest the name 'biTregs '. Importantly, the
      pathogenic biTreg effects were dependent upon expression of RORgammat. We thus
      aimed to evaluate the contribution of RORgammat+ FoxP3+ biTregs to pristane
      induced SLE and explored the therapeutic potential of interference with RORgammat
      activation. Our analyses revealed expansion of IL-17 producing biTregs in a
      distinctive time-course and organ-specific pattern, coincident with the
      development of autoimmunity and tissue injury. Importantly, specific ablation of
      RORgammat activation in endogenous biTregs resulted in significant amelioration
      of pristane-induced pulmonary vasculitis and lupus nephritis. As potential
      mechanisms underlying the observed protection, we found that secretion of IL-17
      by biTregs was abrogated completely in FoxP3Cre  * RORCfl/fl mice. Furthermore,
      Tregs showed a more activated phenotype after cell-specific inactivation of
      RORgammat signalling. Finally, and remarkably, biTregs were found to potently
      suppress anti-inflammatory Th2 immunity in a RORgammat-dependent manner. Our
      study thus identifies biTregs as novel players in SLE and advocates RORgammat
      directed interventions as promising therapeutic strategies.

PMID- 27880976
TI  - A novel quantitative microarray antibody capture assay identifies an extremely
      high hepatitis delta virus prevalence among hepatitis B virus-infected
      mongolians.
AB  - : Hepatitis delta virus (HDV) causes the most severe form of human viral
      hepatitis. HDV requires a hepatitis B virus (HBV) coinfection to provide HDV with
      HBV surface antigen envelope proteins. The net effect of HDV is to make the
      underlying HBV disease worse, including higher rates of hepatocellular carcinoma.
      Accurate assessments of current HDV prevalence have been hampered by the lack of
      readily available and reliable quantitative assays, combined with the absence of
      a Food and Drug Administration-approved therapy. We sought to develop a
      convenient assay for accurately screening populations and to use this assay to
      determine HDV prevalence in a population with abnormally high rates of
      hepatocellular carcinoma. We developed a high-throughput quantitative microarray
      antibody capture assay for anti-HDV immunoglobulin G wherein recombinant HDV
      delta antigen is printed by microarray on slides coated with a noncontinuous,
      nanostructured plasmonic gold film, enabling quantitative fluorescent detection
      of anti-HDV antibody in small aliquots of patient serum. This assay was then used
      to screen all HBV-infected patients identified in a large randomly selected
      cohort designed to represent the Mongolian population. We identified two
      quantitative thresholds of captured antibody that were 100% predictive of the
      sample either being positive on standard western blot or harboring HDV RNA
      detectable by real-time quantitative PCR. Subsequent screening of the HBV+ cohort
      revealed that a remarkable 57% were RNA+ and an additional 4% were positive on
      western blot alone. CONCLUSION: The quantitative microarray antibody capture
      assay's unique performance characteristics make it ideal for population
      screening; its application to the Mongolian HBV surface antigen-positive
      population reveals an apparent ~60% prevalence of HDV coinfection among these HBV
      infected Mongolian subjects, which may help explain the extraordinarily high rate
      of hepatocellular carcinoma in Mongolia. (Hepatology 2017;66:1739-1749).

PMID- 27880977
TI  - Bariatric surgery for nonalcoholic steatohepatitis: A clinical and cost
      effectiveness analysis.
AB  - : Nonalcoholic steatohepatitis (NASH) affects 2%-3% of the US population and is
      expected to become the leading indication for liver transplantation in the next
      decade. Bariatric surgery may be an effective but expensive treatment for NASH.
      Using a state-transition model, our analysis assessed the effectiveness and cost
      effectiveness of surgery to manage NASH. We simulated the benefits and harms of
      laparoscopic Roux-en-Y gastric bypass surgery in patients defined by weight class
      (overweight, mild obesity, moderate obesity, and severe obesity) and fibrosis
      stage (F0-F3). Comparators included intensive lifestyle intervention (ILI) and no
      treatment. Quality-adjusted life years (QALYs), costs, and incremental cost
      effectiveness ratios were calculated. Our results showed that surgery and ILI in
      obese patients (with F0-F3) increased QALYs by 0.678-2.152 and 0.452-0.618,
      respectively, compared with no treatment. Incremental cost-effectiveness ratios
      for surgery in all F0-F3 patients with mild, moderate, or severe obesity were
      $48,836/QALY, $24,949/QALY, and $19,222/QALY, respectively. In overweight
      patients (with F0-F3), surgery increased QALYs by 0.050-0.824 and ILI increased
      QALYs by 0.031-0.164. In overweight patients, it was cost-effective to reserve
      treatment only for F3 patients; the incremental cost-effectiveness ratios for
      providing surgery or ILI only to F3 patients were $30,484/QALY and $25,367/QALY,
      respectively. CONCLUSIONS: Surgery was both effective and cost-effective for
      obese patients with NASH, regardless of fibrosis stage; in overweight patients,
      surgery increased QALYs for all patients regardless of fibrosis stage, but was
      cost-effective only for patients with F3 fibrosis; our results highlight the
      promise of bariatric surgery for treating NASH and underscore the need for
      clinical trials in this area. (Hepatology 2017;65:1156-1164).

PMID- 27880978
TI  - Defining the relationship between farsenoid X receptor, hepatitis B virus X
      protein and hepatocellular carcinoma: It's complicated.

PMID- 27880979
TI  - Low-Dose Lipopolysaccharide Causes Biliary Injury by Blood Biliary Barrier
      Impairment in a Rat Hepatic Ischemia/Reperfusion Model.
AB  - This study explored whether bacterial endotoxins, in the form of
      lipopolysaccharides (LPS), could have an injurious effect on the biliary tract in
      conjunction with ischemia. A total of 64 rats were randomly assigned to 4 groups:
      sham operation (sham group), 1 mg/kg LPS intraperitoneal (LPS group), hepatic
      ischemia/reperfusion (IR; IR group), and IR combined with LPS (IR+LPS group).
      Following 1 or 6 hours of reperfusion, serum liver tests, bile duct histology,
      immunofluorescence microscopy (zonula occludens-1 [ZO-1]), bile composition (bile
      salts, phospholipids, lactate dehydrogenase), hepatic gene expression (bile salt
      transporters and inflammatory mediators), as well as serum and biliary cytokine
      concentrations were quantified and compared between the study groups. In
      addition, the integrity of the blood biliary barrier (BBB) was assayed in vivo
      using horseradish peroxidase (HRP). LPS administration induced severe small bile
      duct injury following 6 hours of reperfusion. Furthermore, total bile salts and
      bilirubin concentrations in serum were increased in the LPS groups compared with
      sham controls (LPS, + 3.3-fold and +1.9-fold; IR+LPS, + 3.8-fold and +1.7-fold,
      respectively). The BBB was impaired in the LPS groups as evidenced by elevated
      levels of HRP in bile (+4.9-fold), and decreased expression of claudin 1 (-6.7
      fold) and claudin 3 (-3.6-fold). LPS was found to be a potent inducer of small
      bile duct injury following hepatic ischemia and 6 hours of reperfusion. This
      injury was associated with increased permeability of the BBB and impaired hepatic
      bile salt clearance. Liver Transplantation 23 194-206 2017 AASLD.

PMID- 27880980
TI  - Impact of total body irradiation on successful neutrophil engraftment in
      unrelated bone marrow or cord blood transplantation.
AB  - Total body irradiation (TBI) has been thought to promote donor cell engraftment
      in allogeneic hematopoietic cell transplantation (HCT) from alternative donors.
      However, recent progress in HCT strategies may affect the clinical significance
      of TBI on neutrophil engraftment. With the use of a Japanese transplant registry
      database, we analyzed 3933 adult recipients (>15 y.o.) who underwent HCT between
      2006 and 2013 from an 8/8 HLA-matched unrelated bone marrow donor (MUD, n =
      1367), an HLA-mismatched unrelated bone marrow donor (MMUD, n = 1102), or
      unrelated cord blood (CBT, n = 1464). Conditioning regimens were divided into
      five groups: High-TBI-(>8Gy), Low-TBI- (<=8Gy), and no-TBI-myeloablative
      conditioning (MAC), and Low-TBI- and no-TBI-reduced-intensity conditioning (RIC).
      In both MUD and MMUD, neutrophil engraftment rate was >90% in each of the five
      conditioning groups, and TBI was not associated with prompt neutrophil
      engraftment in multivariate analyses. Conversely, in CBT, TBI regimens had a
      higher rate of day-30 neutrophil engraftment than no-TBI-regimens: 78% in High
      TBI-MAC, 83% in Low-TBI-MAC, and 76% in Low-TBI-RIC versus 65% in No-TBI-MAC, and
      68% in No-TBI-RIC (P < .001). Multivariate analyses in CBT demonstrated that TBI
      regimens were significantly associated with a higher rate of neutrophil
      engraftment. Subsequently focusing on CBT patients alone, TBI-regimens were
      significantly associated with a higher rate of neutrophil engraftment in patients
      who received CBT with a 4/6 or less HLA allele-match, or who had anti-HLA
      antibodies. In summary, TBI-regimens had no impact on neutrophil engraftment in
      the current practice of unrelated bone marrow transplantation. However, in CBT,
      TBI is still necessary to enhance engraftment.

PMID- 27880981
TI  - A novel glucagon-like peptide 1/glucagon receptor dual agonist improves
      steatohepatitis and liver regeneration in mice.
AB  - : Because nonalcoholic steatohepatitis (NASH) is associated with impaired liver
      regeneration, we investigated the effects of G49, a dual glucagon-like peptide
      1/glucagon receptor agonist, on NASH and hepatic regeneration. C57Bl/6 mice fed
      chow or a methionine and choline-deficient (MCD) diet for 1 week were divided
      into 4 groups: control (chow diet), MCD diet, chow diet plus G49, and M+G49 (MCD
      diet plus G49). Mice fed a high-fat diet (HFD) for 10 weeks were divided into
      groups: HFD and H+G49 (HFD plus G49). Following 2 (MCD groups) or 3 (HFD groups)
      weeks of treatment with G49, partial hepatectomy (PH) was performed, and all mice
      were maintained on the same treatment schedule for 2 additional weeks. Analysis
      of liver function, hepatic regeneration, and comprehensive genomic and metabolic
      profiling were conducted. NASH was ameliorated in the M+G49 group, manifested by
      reduced inflammation, steatosis, oxidative stress, and apoptosis and increased
      mitochondrial biogenesis. G49 treatment was also associated with replenishment of
      intrahepatic glucose due to enhanced gluconeogenesis and reduced glucose use
      through the pentose phosphate cycle and oxidative metabolism. Following PH, G49
      treatment increased survival, restored the cytokine-mediated priming phase, and
      enhanced the proliferative capacity and hepatic regeneration ratio in mice on the
      MCD diet. NASH markers remained decreased in M+G49 mice after PH, and glucose use
      was shifted to the pentose phosphate cycle and oxidative metabolism. G49
      administered immediately after PH was also effective at alleviating the
      pathological changes induced by the MCD diet. Benefits in terms of liver
      regeneration were also found in mice fed HFD and treated with G49. CONCLUSION:
      Dual-acting glucagon-like peptide-1/glucagon receptor agonists such as G49
      represent a novel therapeutic approach for patients with NASH and particularly
      those requiring PH. (Hepatology 2017;65:950-968).

PMID- 27880983
TI  - Pantoea ananatis: genomic insights into a versatile pathogen.
AB  - : Pantoea ananatis, a bacterium that is well known for its phytopathogenic
      characteristics, has been isolated from a myriad of ecological niches and hosts.
      Infection of agronomic crops, such as maize and rice, can result in substantial
      economic losses. In the last few years, much of the research performed on P.
      ananatis has been based on the sequencing and analysis of the genomes of strains
      isolated from different environments and with different lifestyles. In this
      review, we summarize the advances made in terms of pathogenicity determinants of
      phytopathogenic strains of P. ananatis and how this bacterium is able to adapt
      and survive in such a wide variety of habitats. The diversity and adaptability of
      P. ananatis can largely be attributed to the plasticity of its genome and the
      integration of mobile genetic elements on both the chromosome and plasmid.
      Furthermore, we discuss the recent interest in this species in various
      biotechnological applications. TAXONOMY: Domain Bacteria; Class
      Gammaproteobacteria; Family Enterobacteriaceae; genus Pantoea; species ananatis.
      DISEASE SYMPTOMS: Pantoea ananatis causes disease on a wide range of plants, and
      symptoms can range from dieback and stunted growth in Eucalyptus seedlings to
      chlorosis and bulb rotting in onions. DISEASE CONTROL: Currently, the only
      methods of control of P. ananatis on most plant hosts are the use of resistant
      clones and cultivars or the eradication of infected plant material. The use of
      lytic bacteriophages on certain host plants, such as rice, has also achieved a
      measure of success.

PMID- 27880982
TI  - Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with
      myeloproliferative neoplasms.
AB  - Splanchnic vein thrombosis (SVT) is one of the vascular complications of
      myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to
      evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and
      improving disease-related symptoms in patients with MPN-associated SVT. Patients
      diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and
      essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core
      study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and
      splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried
      JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients
      had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one
      had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well
      tolerated with hematological toxicities consistent with those of patients without
      SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment,
      spleen volume reduction >=35% by MRI was achieved by 6/21 (29%) patients, and a
      >=50% spleen length reduction by palpation at any time up to week 24 was obtained
      by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the
      spleen response by palpation. No significant effect of treatment on esophageal
      varices or in splanchnic circulation was observed. MPN-related symptoms,
      evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved
      significantly during the first 4 weeks and remained stable up to week 24. In
      conclusion, this trial shows that ruxolitinib is safe in patients with MPN
      associated SVT, and effective in reducing spleen size and disease-related
      symptoms.

PMID- 27880985
TI  - Daily pain in adults with sickle cell disease-a different perspective.
AB  - Previous reports demonstrated that patients with sickle cell disease (SCD)
      experience pain on more than half of the observed days. Yet, these high
      incidences do not seem to match observations in our population. In this
      prospective cohort study, we aimed to assess the frequency and characteristics of
      daily, self-reported pain among adult SCD patients in the Netherlands.
      Consecutive patients were enrolled during routine outpatient visits and followed
      up to 6 months. A total of 55 patients completed 5,982 diary observation days.
      Median age was 27 years (IQR 23-43). Patients reported SCD related pain on 17% of
      the observed days; on 13% of these days this pain was not defined as a painful
      crisis, while 3% was reported as a painful crisis but managed at home, and on 1%
      of the observed days patients were admitted to the hospital. Analgesics were used
      on 52% of days with pain with a relatively infrequent use of oral opioids (9% of
      pain days). This first European study on pain in SCD indicates that pain appears
      to be significantly less frequent in our population as compared to previous study
      cohorts from the United States, and may be more representative for current SCD
      populations in other Western countries. Besides a more widespread use of
      hydroxycarbamide in modern disease management, differences in organization and
      accessibility of healthcare between countries may also explain this discrepancy.

PMID- 27880984
TI  - Diffuse large B-cell lymphoma with primary treatment failure: Ultra-high risk
      features and benchmarking for experimental therapies.
AB  - The outcomes of patients with DLBCL and primary treatment failure (PTF) in the
      rituximab era are unclear. We analyzed 331 patients with PTF, defined as primary
      progression while on upfront chemoimmunotherapy (PP), residual disease at the end
      of upfront therapy (RD) or relapse < 6 months from end of therapy (early relapse;
      ER). Median age was 58 years and response to salvage was 41.7%. Two-year OS was
      18.5% in PP, 30.6% in RD and 45.5% in ER. The presence of PP, intermediate
      high/high NCCN-IPI at time of PTF or MYC translocation predicted 2-year OS of
      13.6% constituting ultra-high risk (UHR) features. Among the 132 patients who
      underwent autologous hematopoietic cell transplantation, 2-year OS was 74.3%,
      59.6% and 10.7% for patients with 0,1 and 2-3 UHR features respectively. Patients
      with PTF and UHR features should be prioritized for clinical trials with newer
      agents and innovative cellular therapy.

PMID- 27880986
TI  - Nutrients, amino acid, fatty acid and non-starch polysaccharide profile and in
      vitro digestibility of macadamia nut cake in swine.
AB  - The highly variable cost and limited availability of conventional feedstuffs make
      it imperative to explore alternative feedstuffs to be used in swine. Macadamia
      nut cake (MNC), a coproduct of the macadamia nut oil industry, has not been well
      studied. MNC was analyzed for its nutrient profile, gross energy (GE), fibers,
      amino acids and fatty acids content. Dry matter (DM) and GE digestibility of MNC
      in swine was determined using an in vitro model. On a DM basis, ash, crude
      protein, ether extract, NDF, ADF, lignin and GE were found to be 3.7, 25.5, 11.9,
      35.8, 28.0, 16.0% and 5581 kcal/kg, respectively. Total and soluble non-starch
      polysaccharide content were 32.2 and 11.8%, respectively. The concentration of
      lysine was found to be 0.7%. The DM and GE digestibility were found to be 75.7
      and 71.4%, respectively. Gross energy content of MNC is comparable with that of
      corn and higher than soybean meal, while protein content is twice as high as corn
      but lower than soybean meal. In conclusion, MNC is not merely a good source of
      protein and energy but also has fairly high digestibility in swine. Hence, it can
      be used as a viable alternative source of energy and protein in swine diets.

PMID- 27880988
TI  - Pioglitazone for advanced fibrosis in nonalcoholic steatohepatitis: New evidence,
      new challenges.

PMID- 27880987
TI  - Assessing surgical research at the teaching hospital level.
AB  - BACKGROUND: To undertake a comprehensive needs assessment to determine the
      baseline of surgical research activity at a tertiary referral hospital in Sydney,
      Australia. METHOD: The comprehensive needs assessment comprised three components:
      a retrospective audit of the hospital ethics committee records to identify
      surgical research activity; a survey of all 17 surgical departments about the
      availability of 10 potential research resources and a survey of surgical staff to
      ascertain perceptions of research culture at the organizational, team and
      individual levels. RESULTS: Of all research studies submitted to the hospital
      ethics committee in a 2-year period, only 9% were identified as surgical studies.
      Among the 17 surgical departments, there was wide variation in activity with only
      four defined as being 'research active'. On average, 52% of potential resources
      for surgical research were found to be in place within surgical departments. Only
      five departments were considered to be adequately research resourced (>=75%
      potential resources in place). Surgical research culture was rated 'moderate' at
      the organizational and team level, and 'low' at the individual level. Medical
      staff rated research capacity significantly higher at the team and individual
      levels compared to nursing staff. CONCLUSION: Collectively, the baseline results
      indicate there is considerable opportunity to enhance surgical research at the
      hospital level and to use this information to guide new and innovative approaches
      in the future.

PMID- 27880989
TI  - Validation of the prognostic value of histologic scoring systems in primary
      sclerosing cholangitis: An international cohort study.
AB  - : Histologic scoring systems specific for primary sclerosing cholangitis (PSC)
      are not validated. We recently determined the applicability and prognostic value
      of three histological scoring systems in a single PSC cohort. The aim of this
      study was to validate their prognostic use and reproducibility across a
      multicenter PSC cohort. Liver biopsies from PSC patients were collected from
      seven European institutions. Histologic scoring was performed using the Nakanuma,
      Ishak, and Ludwig scoring systems. Biopsies were independently scored by six
      liver pathologists for interobserver agreement. The prognostic value of clinical,
      biochemical, and all three histologic scoring systems on predicting composite
      endpoints 1 (PSC-related death and liver transplantation), 2 (liver
      transplantation), and 3 (liver-related events), was assessed using univariable
      and multivariable Cox proportional hazards modeling. A total of 119 PSC patients
      were identified, and the median follow-up was 142 months. During follow-up, 31
      patients died (20 PSC-related deaths), 31 patients underwent liver
      transplantation, and 35 patients experienced one or more liver-related events.
      All three staging systems were independent predictors of endpoints 2 and 3
      (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49
      6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17-3.57] for endpoint 3; Ishak
      system: HR, 1.55 [95% CI, 1.10-2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10
      1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19-5.80] for endpoint 2
      and HR, 2.06 [95% CI, 1.09-3.89] for endpoint 3). Only the Nakanuma staging
      system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22
      3.77). Interobserver agreement was moderate for Nakanuma stage (kappa = 0.56) and
      substantial for Nakanuma component fibrosis (kappa = 0.67), Ishak stage (kappa =
      0.64), and Ludwig stage (kappa = 0.62). CONCLUSION: We confirm the independent
      prognostic value and demonstrate for the first time the reproducibility of
      staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging
      systems. The Nakanuma staging system-incorporating features of chronic biliary
      disease-again showed the strongest predictive value. (Hepatology 2017;65:907
      919).

PMID- 27880990
TI  - Neurodegeneration and NLRP3 inflammasome expression in the anterior thalamus of
      SOD1(G93A) ALS mice.
AB  - Nowadays, amyotrophic lateral sclerosis (ALS) is considered as a multisystem
      disorder, characterized by a primary degeneration of motor neurons as well as
      neuropathological changes in non-motor regions. Neurodegeneration in subcortical
      areas, such as the thalamus, are believed to contribute to cognitive and
      behavioral abnormalities in ALS patients. In the present study, we investigated
      neurodegenerative changes including neuronal loss and glia pathology in the
      anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model
      for ALS. We detected massive dendrite swelling and neuronal loss in SOD1(G93A)
      animals, which was accompanied by a mild gliosis. Furthermore, misfolded SOD1
      protein and autophagy markers were accumulating in the AD. Since innate immunity
      and activation inflammasomes seem to play a crucial role in ALS, we examined
      protein expression of Nod-like receptor protein 3 (NLRP3), apoptosis-associated
      speck-like protein containing a caspase-1 recruitment domain (ASC) and the
      cytokine interleukin 1 beta (IL1beta) in AD glial cells and neurons. NLRP3 and
      ASC were significantly up-regulated in the AD of SOD1(G93A) mice. Finally, co
      localization studies revealed expression of NLRP3, ASC and IL1beta in neurons.
      Our study yielded two main findings: (i) neurodegenerative changes already occur
      at an early symptomatic stage in the AD and (ii) increased inflammasome
      expression may contribute to neuronal cell death. In conclusion,
      neurodegeneration in the anterior thalamus may critically account for cognitive
      changes in ALS pathology.

PMID- 27880991
TI  - Vascular complications in living donor liver transplantation at a high-volume
      center: Evolving protocols and trends observed over 10 years.
AB  - Vascular complications continue to have a devastating effect on liver
      transplantation recipients, even though their nature, incidence, and outcome
      might have actually changed with increasing experience and proficiency in high
      volume centers. The aim of this study was to analyze the trends observed in
      vascular complications with changing protocols in adult and pediatric living
      donor liver transplantation over 10 years in 2 time frames in terms of nature,
      incidence, and outcome. It is a retrospective analysis of 391 (group 1, January
      2006 to December 2010) and 741 (group 2, January 2011 to October 2013) patients.
      With a minimum follow-up of 2 years, incidence of hepatic artery thrombosis (HAT)
      in adults has reduced significantly from 2.2% in group 1 to 0.5% in group 2 (P =
      0.02). In group 2, nonsignificantly, more adult patients (75% with HAT) could be
      salvaged compared with only 25% patients in group 1 (P = 0.12). However, HAT in
      children had 100% mortality. Incidence of portal vein thrombosis (PVT) in
      complicated transplants in 2 eras remained the same (P = 0.2) and so has its
      mortality. The thrombosis rate of the neo-middle hepatic vein was significantly
      reduced in group 2 (P = 0.01). The incidence of HAT, particularly in adults, has
      decreased significantly though PVT has continued to puzzle surgeons in
      complicated transplants. In high-volume centers, increasing proficiency,
      technical modifications, early diagnosis, and multimodality of treatment is the
      key to decrease overall morbidity and mortality due to vascular complications.
      Liver Transplantation 23 457-464 2017 AASLD.

PMID- 27880992
TI  - Studies using concentric ring bifocal and peripheral add multifocal contact
      lenses to slow myopia progression in school-aged children: a meta-analysis.
AB  - PURPOSE: To evaluate the effect of soft contact lens with concentric ring bifocal
      and peripheral add multifocal designs on controlling myopia progression in school
      aged children. METHODS: We systematically searched MEDLINE, EMBASE, Cochrane
      Library and reference lists of included trials. Methodological quality of
      included trials was assessed using Jadad Scale and Newcastle-Ottawa Quality
      Assessment Scale items. RESULTS: We identified five randomised controlled trials
      (RCTs) and three cohort studies with a total of 587 myopic children. Compared
      with the control group, concentric ring bifocal soft contact lenses showed less
      myopia progression with a weighted mean difference (WMD) of 0.31 D (95% CI,
      0.05~0.57 D, p = 0.02) and less axial elongation with a WMD of -0.12 mm (95% CI,
      approximately -0.18 to -0.07 mm, p < 0.0001) at 12 months. Relative to the
      control group, peripheral add multifocal soft contact lenses showed less myopia
      progression with a WMD of 0.22 D (95% CI 0.14~0.31 D, p < 0.0001) and less axial
      elongation of -0.10 mm (95% CI -0.13~0.07 mm, p < 0.0001) at 12 months,
      respectively. The soft contact lenses with concentric ring bifocal and peripheral
      add multifocal designs produced additional myopia control rates of 30~38% for
      slowing myopia progression and 31~51% for lessening axial elongation within 24
      months. CONCLUSIONS: Both concentric ring bifocal and peripheral add multifocal
      soft contact lenses are clinically effective for controlling myopia in school
      aged children, with an overall myopia control rates of 30~50% over 2 years.
      Concentric ring bifocal soft contact lenses seem to have greater effect than
      peripheral add multifocal soft contact lenses.

PMID- 27880994
TI  - Isothiocyanates in Brassica: Potential Anti Cancer Agents
AB  - Isothiocyanates are naturally occurring small molecules that are formed from
      glucosinolate precursors ofcruciferous vegetables. Many isothiocyanates, both
      natural and synthetic, display anti-carcinogenic activitybecause they reduce
      activation of carcinogens and increase their detoxification. This minireview
      summarizesthe current knowledge on isothiocyanates and focuses on their role as
      potential anti-cancer agents.

PMID- 27880993
TI  - Clinical Factors Predictive of Metastases from Renal Cell Carcinomas
AB  - Background: Lymph node and distant metastases are known as the prognostic factor
      in renal cell carcinoma (RCC). Clinical parameters are needed to predict
      metastases preoperatively. The aim of this study was to assessclinical predictive
      factors for lymph node and distant metastases. Materials and Methods: We
      collected RCCdata from January 1995 until December 2015 at Cipto Mangunkusumo
      hospital in Jakarta. We only revieweddata that had renal cell carcinoma
      histopathology by operation or biopsy. Clinical information such as patientage,
      gender, hemoglobin (Hb), erythrocyte sedimentation rate (ESR), and tumor size
      (clinical T stage) werereviewed and analyzed by Chi-squre and logistic regression
      to establish clinical predictive value. Results: A totalof 102 patients were
      reviewed. There were 32 (31.4%) with lymph node metastases and 27 (26.5%) with
      distantmetastases. Age, Hb and clinical T staging were associated with nodal
      metastases. However, only Hb and clinicalT staging were found to be associated
      with distant metastases. By logistic regression, we found T3-4 in clinicalT-stage
      to be the only predictor of nodal metastases (OR 5.14; 1.87 - 14.09) and distant
      metastases (OR 3.42;1.27 - .9.23). Conclusions: Clinical T-stages of T3 and T4
      according to The AJCC TNM classification could beused as independent clinical
      predictive factors for lymph node or distant metastases in patients with RCC.

PMID- 27880995
TI  - Frequency of K-RAS and N-RAS Gene Mutations in Colorectal Cancers in Southeastern
      Iran
AB  - Background: K-RAS and N-RAS gene mutations cause resistance to treatment in
      patients with colorectalcancer. Based on this, awareness of mutation of these
      genes is considered a clinically important step towardsbetter diagnosis and
      appropriate treatment. Materials and Methods: Fifty paraffin-embedded blocks of
      colorectalcancer were obtained from Imam Reza Hospital of Birjand, Iran.
      Following DNA extraction, the sampleswere analyzed for common mutations of exons
      2, 3 and 4 of KRAS and NRAS genes using real time PCR andpyrosequencing. Results:
      According to this study, the prevalence of mutations was respectively 28% (14 out
      of50) and 2% (1 out of 50) in KRAS and NRAS genes. All the mutations were
      observed in patients >50 years old.Conclusions: Mutations were found in both KRAS
      and NRAS genes in colorectal cancers in Iranian patients.Determining the
      frequency of these mutations in each geographical region may be necessary to
      benefit fromtargeted cancer therapy.

PMID- 27880996
TI  - Oxidative Stress Induced Damage to Paternal Genome and Impact of Meditation and
      Yoga - Can it Reduce Incidence of Childhood Cancer?
AB  - Background: Sperm DNA damage is underlying aetiology of poor implantation and
      pregnancy rates but alsoaffects health of offspring and may also result in denovo
      mutations in germ line and post fertilization. This mayresult in complex
      diseases, polygenic disorders and childhood cancers. Childhood cancer like
      retinoblastoma (RB)is more prevalent in developing countries and the incidence of
      RB has increased more than three fold in India inthe last decade. Recent studies
      have documented increased incidence of cancers in children born to fathers
      whoconsume alcohol in excess and tobacco or who were conceived by assisted
      conception. The aetiology of childhoodcancer and increased disease burden in
      these children is lin ked to oxidative stress (OS) and oxidative DNAdamage( ODD)
      in sperm of their fathers. Though several antioxidants are in use to combat
      oxidative stress, theeffect of majority of these formulations on DNA is not
      known. Yoga and meditation cause significant decline inOS and ODD and aid in
      regulating OS levels such that reactive oxygen speues meditated signal
      transduction, geneexpression and several other physiological functions are not
      disrupted. Thus, this study aimed to analyze spermODD as a possible etiological
      factor in childhood cancer and role of simple life style interventions like yoga
      andmeditation in significantly decreasing seminal oxidative stress and oxidative
      DNA damage and thereby decreasingincidence of childhood cancers. Materials and
      Methods: A total of 131 fathers of children with RB (non-familialsporadic
      heritable) and 50 controls (fathers of healthy children) were recruited at a
      tertiary center in India.Sperm parameters as per WHO 2010 guidelines and reactive
      oxygen species (ROS), DNA fragmentation index(DFI), 8-hydroxy-2'-deoxy guanosine
      (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6months of
      intervention. We also examined the compliance with yoga and meditation practice
      and smoking statusat each follow-up. Results: The seminal mean ROS levels
      (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levelswere significantly higher in
      fathers of children with RB, as compared to controls and the relative mean
      telomerelength in the sperm was shorter. Levels of ROS were significantly reduced
      in tobacco users (p<0.05) as well as inalcoholics (p<0.05) after intervention.
      DFI reduced significantly (p<0.05) after 6 months of yoga and meditationpractice
      in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced
      significantly after 3months (p<0.05) and 6 months (p<0.05) of practice.
      Conclusions: Our results suggest that OS and ODD DNAmay contribute to the
      development of childhood cancer. This may be due to accumulation of oxidized
      mutagenicbase 8OHdG , and elevated MDA levels which results in MDA dimers which
      are also mutagenic, aberrantmethylation pattern, altered gene expression which
      affect cell proliferation and survival through activation oftranscription
      factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due
      to highlytruncatred DNA repair mechanisms all contribute to sperm genome
      hypermutability and persistant oxidativeDNA damage. Oxidative stress is also
      associated with genome wide hypomethylation, telomere shortening andmitochondrial
      dysfunction leading to genome hypermutability and instability. To the best of our
      knowledge, thisis the first study to report decline in OS and ODD and improvement
      in sperm DNA integrity following adoptionof meditation and yoga based life style
      modification.This may reduce disease burden in next generation andreduce
      incidence of childhood cancers.

PMID- 27880999
TI  - Current knowledge on the active form of Vitamin D synthesized in the skin and its
      effects on malignant melanoma.
AB  - The link between sunlight and skin cancer is a frequently discussed topic.
      However, ultraviolet radiation also induces the production of Vitamin D in the
      body. Keratinocytes and their ability to synthesize the active form of Vitamin D,
      which is consumed at the place of its origin in the skin, have a unique place in
      this discussion. We observe a remarkable sunshine-related paradox when we monitor
      the relationship between the dose of solar radiation and one type of skin cancer 
      malignant melanoma. Recent knowledge of the non-calcemic effects of Vitamin D,
      which include growth regulation, DNA repair, differentiation, apoptosis, membrane
      transport, metabolism, cell adhesion and oxidative stress, could help to further
      clarify this relationship. In this context, adjuvant Vitamin D therapy is
      currently being considered in patients with malignant melanoma, and this is
      expected to reduce tumor invasiveness and micrometastases and thus improve
      patient prognosis and reduce the risk of relapse.

PMID- 27880997
TI  - Efficacy of switching from adefovir to tenofovir in chronic hepatitis B patients
      who exhibit suboptimal responses to adefovir-based combination rescue therapy due
      to resistance to nucleoside analogues (SATIS study).
AB  - BACKGROUND/AIMS: It remains to be determined whether switching from adefovir
      (ADV) to tenofovir (TDF) provides better virological outcomes in patients
      exhibiting suboptimal responses to ADV plus nucleoside analogue (ADV+NA) therapy
      for NA-resistant chronic hepatitis B (CHB). METHODS: In this prospective trial,
      patients who showed partial responses (defined as serum hepatitis B virus [HBV]
      DNA >60 IU/mL) to ADV+NA therapy for NA resistance were randomly allocated to
      receive TDF plus NA (TDF+NA group, n=16) or to continue their current therapy
      (ADV+NA group, n=16). The primary end point was the proportion of patients with
      complete virological response (CVR, defined as serum HBV DNA <60 IU/mL) at 48
      weeks. RESULTS: The median age was 52 years (16 men), and 28 were positive for
      hepatitis B e antigen (HBeAg). The baseline characteristics did not differ
      significantly between the two groups. The proportion with CVR was significantly
      higher in the TDF+NA group than in the ADV+NA group at 24 weeks (81.3% vs. 25.0%,
      P=0.001) and 48 weeks (87.5% vs. 37.5%, P=0.002). Furthermore, a decrease in the
      serum HBV DNA level of >2log10 IU/mL was more likely in the TDF+NA group at both
      24 and 48 weeks (68.8% vs. 56.3%, P=0.014 vs. 81.3% vs. 56.3%, P=0.001,
      respectively). During the follow-up, the rate of HBeAg seroconversion was higher
      in the TDF+NA group than the ADV+NA group (12.5% vs. 6.25%, P=0.640), as was that
      for the hepatitis B surface antigen (6.25% vs. 0%, P=0.080). No serious adverse
      events due to antiviral agents occurred. CONCLUSION: In patients exhibiting
      suboptimal responses to ADV+NA therapy for NA-resistant CHB, switching from ADV
      to TDF might provide better virological outcomes.

PMID- 27881000
TI  - MicroRNA-584-3p reduces the vasculogenic mimicry of human glioma cells by
      regulating hypoxia-induced ROCK1 dependent stress fiber formation.
AB  - We report in this study that microRNA-584-3p (miR-584-3p) is related to the
      vasculogenic mimicry (VM) of human glioma cells. Unsurprisingly, the
      postoperative survival time was significantly prolonged in those glioma patients
      without VM phenomena compared with those with positive VM. miR-584-3p may
      function as a potent tumor suppressor by inhibiting VM of malignant glioma.
      However, the molecular mechanisms underlying these properties remain poorly
      understood. Our preliminary mechanistic studies revealed that miR-584-3p
      suppressed the VM by disturbing hypoxia-induced stress fiber formation and
      migration of glioma cells. Specifically, we defined ROCK1 as a potential
      functionally relevant target of miR-584-3p involved in this process in glioma
      cells. Our results demonstrate a tumor suppressor function for miR-584-3p in
      glioma, where it inhibits the VM of tumor cells by antagonizing hypoxia-induced
      ROCK1-dependent stress fiber formation. Our findings have potential implications
      for glioma gene therapy by targeting miR-584-3p and suggest that VM could
      represent a prognostic indicator for gliomas.

PMID- 27880998
TI  - Recurrent acute portal vein thrombosis in liver cirrhosis treated by rivaroxaban.
AB  - Cirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may
      aggravate portal hypertension, and it can lead to hepatic decompensation. The
      international guideline recommends for anticoagulation treatment to be maintained
      for at least 3 months in all patients with acute PVT. Low-molecular-weight
      heparin and changing to warfarin is the usual anticoagulation treatment. However,
      warfarin therapy is problematic due to a narrow therapeutic window and the
      requirement for frequent dose adjustment, which has prompted the development of
      novel oral anticoagulants for overcoming these problems. We report a 63-year-old
      female who experienced complete resolution of recurrent acute PVT in liver
      cirrhosis after treatment with rivaroxaban.

PMID- 27881001
TI  - Pathway crosstalk analysis in prostate cancer based on protein-protein network
      data.
AB  - Prostate cancer (PCa) is one of the major leading cause in men and no effective
      biomarkers or therapy have been approved for it to date. This study aimed to
      explore the molecular mechanisms and identify the potential molecular biomarkers
      of PCa. The microarray profile GSE38241 including 18 prostate cancer metastasis
      and 21 normal prostate samples was retrieved from the Gene Expression Omnibus
      (GEO) database. Differentially expressed genes (DEGs) were identified by Limma.
      DEGs functions were investigated by Gene Ontology (GO) and pathway enrichment
      analysis. Moreover, protein-protein interaction (PPI) network of DEGs was
      constructed, followed by functional analysis of modules. Additionally, pathway
      crosstalk network was constructed by integrating PPI network and Kyoto
      encyclopedia of genes and genomes (KEGG) pathways. Totally, 334 up - and 703 down
      regulated DEGs were identified. The functions of up-regulated DEGs were
      significantly enriched in GO terms of cell cycle phase and cell cycle process.
      While down-regulated DEGs mainly participated in actin filament-based process.
      Among these pathways in the pathway crosstalk network, T cell receptor signaling
      pathway, chemokine signaling pathways, endometrial cancer and glioma were found
      to play critical roles during PC progression. Cell division cycle 45 (CDC45),
      baculoviral IAP repeat containing 5 (BIRC5) and cell division cycle associated 5
      (CDCA5) may be useful markers for predicting tumor metastasis and therapeutic
      targets for the treatment of PCa patients. Moreover, the pathway crosstalk
      network provides the groundwork that targeting multiple pathways might be more
      effective than targeting one pathway alone.

PMID- 27881002
TI  - Expression of orphan GPR56 correlates with tumor progression in human epithelial
      ovarian cancer.
AB  - G protein-coupled receptor 56 (GPR56) has been demonstrated to be a significant
      prognostic predictor in several types of malignances, including melanoma,
      glioblastoma, breast cancer, colon cancer, and pancreatic cancer. GPR56 has a
      putative mucin-like extracellular domain, indicating functions for this receptor
      in the cell-cell interactions and triggering different downstream signaling
      pathways responsible for regulating cell survival, proliferation, adhesion, and
      migration. But the expression and clinical significance of GPR56 has not been
      elucidated in epithelial ovarian cancer (EOC). We detected GPR56 expression by
      immunohistochemistry in 110 samples of ovarian serous carcinoma to explore the
      correlation between its expression and clinicopathologic characteristics and
      overall survival. As the result, we found that GPR56 expression is significantly
      associated with advanced FIGO stage (P = 0.01) and positive lymph node invasion
      (P = 0.016), and it serves as an independent unfavorable prognostic factor
      through univariate and multivariate analysis. GPR56 knockdown could dramatically
      decrease the proliferation and invasion of epithelial ovarian cancer cells
      through down-regulating the RhoA-GTP level and up-regulating the E-cadherin
      level, which indicates GPR56 could promote the progression and invasion of EOC.
      In conclusion, GPR56 expression was demonstrated as an independent prognostic
      factor in EOC, suggesting that GPR56 may play an oncogenic role through the Rho
      and E-cadherin pathway and GPR56 could be a novel potential drug target in EOC.

PMID- 27881003
TI  - miR-508-5p acts as an anti-oncogene by targeting MESDC1 in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer associated
      mortality. Accumulating evidence has shown that microRNAs (miRNAs) act as
      critical factors for tumor recurrence and metastasis. MiR-508-5p has been
      reported as a down-regulated miRNA in the primary gastric cancer tissues.
      However, the role of miR-508-5p on HCC has not been well elucidated. In this
      study, we observed that miR-508-5p was downregulated in HCC tissues when compared
      to the non-tumorous tissues. We then demonstrated that overexpression of miR-508
      5p attenuated HepG2 cells proliferation and invasion and induced cell apoptosis
      in vitro. Furthermore, our further investigations revealed that mesoderm
      development candidate 1 (MESDC1) is a potential target of miR-508-5p, as well as
      miR-508-5p overexpression downregulated MESDC1 expression. Overexpression of
      MESDC1 promoted HepG2 cells migration, invasion and proliferation in vitro. In
      addition, miR-508-5p markedly suppressed the tumor growth in xenograft model,
      while MESDC1 promoted the tumor growth in xenograft model. This study provides
      new insight into molecular mechanisms that miR-508-5p acts as a tumor suppressor
      by targeting MESDC1 in HCC progression.

PMID- 27881004
TI  - Monitoring in real time the effect of TLX overexpression on proliferation and
      migration of C6 cells.
AB  - Orphan nuclear receptor TLX has been shown to play an essential role in
      regulating the self-renewal and proliferation of neural stem cells (NSCs).
      However, TLX overexpression in NSCs induces long-term NSC expansion and further
      leads to glioma initiation in mouse when combined with p53 mutations. Whether
      overexpression of TLX plays a role in glioma stem cell (GSC) proliferation and
      migration still remains largely unknown. In this study, we infected C6 cells, a
      special glioma cell line which is mainly composed of cancer stem cells(CSCs),
      with lentiviruses expressing GFP(LV-GFP) or GFP-T2A-TLX(LV-TLX) and then
      monitored cell proliferation and migration using the real-time analyzer system
      (RTCA, xCELLigence, Roche). We found that the cell index (CI) observed for the
      TLX overexpressing C6 cells showed a lower value than that of the LV-GFP
      transduced cells. And the MTT results correlated highly with the RTCA
      proliferation assessments. Furthermore, the expression of p21 was decreased while
      other downstream genes PTEN and p53 were not significantly changed in TLX
      overexpressing C6 cells . These findings strongly indicate that TLX
      overexpression has the ability to decrease the proliferating and migratory
      properties of C6 cells by targeting p21. Further, our results suggest that TLX
      overexpression may also have a similar inhibitory effect on GSC proliferation and
      migration.

PMID- 27881005
TI  - A microRNA expression signature as a predictor of survival for colon
      adenocarcinoma.
AB  - Colon cancer is a major cause of cancer mortality worldwide and most colon
      cancers are adenocarcinoma. MicroRNA (miRNA) expression signature has been shown
      to be able to predict progression and prognosis of various cancers. The aim of
      our study was to explore a novel signature of microRNA expression for predicting
      survival of colon adenocarcinoma patients. By analyzing the miRNA expression
      profiles and clinical information of 329 colon adenocarcinoma patients derived
      from The Cancer Genome Atlas database. 129 miRNAs were identified to be expressed
      differentially between the cancer and adjacent tissues. Among them, 27 miRNAs
      were found to be associated with the corresponding clinical characteristics of
      the patients. Furthermore, 7 miRNAs (let-7a-2, mir-32, mir-181a-1, mir-197, mir
      328, mir-505 and mir-652) were found to be significantly correlated with the
      patient survival. The risk established by the 7-miRNA signature we built was
      proved be an independent prognostic factor (Hazard ratio [HR] = 2.048; 95% CI =
      1.144-3.664; p, 0.016). In summary, our study identified miRNAs correlated with
      progression and prognosis of colon adenocarcinoma and built a 7-microRNA
      expression signature for prediction of the survival of the patients with colon
      adenocarcinoma.

PMID- 27881006
TI  - Decreased expression of MS4A12 inhibits differentiation and predicts early stage
      survival in colon cancer.
AB  - Lack of normal differentiation was considered as a common defect in cancer cells.
      MS4A12, a colon-specific gene, belongs to MS4A family that plays an important
      role in differentiation, proliferation and cell cycle regulation. The aim of the
      study was to investigate MS4A12 role in colon cancer cell differentiation and its
      prognostic value in colon cancer. We used sodium butyrate (BS) to set up
      differentiated model of colon cancer cell line LoVo. Cell differentiation was
      evaluated with ALP activity and E-cadherin. We used BS (4 mmol/L) inducing
      differentiation of LoVo cell and found after BS treated over 48h MS4A12 variant-1
      (one of MS4A12 gene transcripts) as well as ALP and E-cadherin of LoVo cells were
      all increased significantly. When silence MS4A12 variant-1, the elevation of ALP
      and E-cadherin in BS-treated cells were all inhibited. Besides, after silence
      MS4A12 variant-1, the cells showed significant resistances to BS function of
      induction cell cycle arrest and apoptosis. Survival analysis used GEO datasets
      GSE39582 and GSE38832 that include 681 distinct colon cancer samples. Log-rank
      test and Cox's proportional hazards regression were applied to analyzing single
      and multiple prognostic variables, respectively. In early stage colon cancer, the
      patients with low MS4A12 expression had a poor survival (HR=1.72; p=0.036), while
      in advanced stage colon cancer MS412 had little prognostic value (HR=0.89;
      p=0.601). These results indicated MS4A12 might relate to colon cancer cell
      differentiation and supposed to be a risk classification marker for early stage
      colon cancer.

PMID- 27881007
TI  - EGCG sensitizes human nasopharyngeal carcinoma cells to TRAIL-mediated apoptosis
      by activation NF-kappaB.
AB  - Aim of presented study was to investigate whether EGCG could sensitize TRAIL
      resistant NPC cells to TRAIL-mediated apoptosis. Three human NPC cell-lines CNE
      1, CNE-2, C666-1 and a non-transformed nasopharyngeal epithelium cell-line NP-69
      were treated with EGCG or/and TRAIL. The apoptosis and TRAIL receptors were
      determined by flow cytometric analysis. The protein expression was determined by
      western blotting. Mitochondrial transmembrane potential was dertemined by DiOC6
      (3). C666-1 cell-line was the only one that resistant to TRAIL and selected to be
      treated with EGCG. ECGC could sensitize C666-1 to TRAIL. Combinatorial treatments
      led to decrease expression of Bcl-XL, Bcl-2, FADD and FLIP and enhance activation
      of capase-3, -8, -9. The DiOC6 (3) negative cell rate was increased and p65 of NF
      kappaB, XIAP and survivin expression was reduced by the combination treatment.In
      summary, EGCG sensitizes NPC cells to TRAIL-mediated apoptosis via modulation of
      extrinsic and intrinsic apoptotic pathways and inhibition of NF-kappaB
      activation.

PMID- 27881008
TI  - miR-33a expression sensitizes Lgr5+ HCC-CSCs to doxorubicin via ABCA1.
AB  - Cancer stem cells (CSCs) are responsible for the unrestrained cell growth and
      chemo-resistance of malignant tumors. Reports about miR-33a in different type of
      cancer are limited, and it remains elusive whether there is a link between miR
      33a and chemo-resistance of CSCs. Here we report that Lgr5+ hepatocellular
      carcinoma (HCC) cells from primary tissues and cell lines behave similarly to
      CSCs and are chemo-resistant to doxorubicin. Significantly, reduced miR-33a
      expression is associated with the chemo-resistance of Lgr5+ HCC-CSCs, accompanied
      by an overexpression of ABCA1 which is identified as target of miR-33a by mainly
      using miRNA luciferase assay and western-blotting. We demonstrate that down
      regulation of miR-33a expression directly contributes to chemo-resistance of
      Lgr5+ HCC-CSCs, and restoring miR-33a expression sensitizes them to doxorubicin
      via apoptosis by mainly using TUNEL assay, soft agar colony formation assay and
      xenograft assay. Additionally, reduced miR-33a expression in HCC tissues is
      associated with chemo-response and poor patient survival, which suggests the
      therapeutic potential of miR-33a. In conclusion, our work indicates that ectopic
      miR-33a expression sensitizes Lgr5+ HCC-CSCs to doxorubicin via direct targeting
      ABCA1, which sheds new light on understanding the mechanism of chemo-resistance
      in HCC-CSCs and contributes to development of potential therapeutics against HCC.

PMID- 27881009
TI  - Late cardiac effect of anthracycline therapy in physically active breast cancer
      survivors - a prospective study.
AB  - The late-onset cardiotoxic effect of anthracycline is known, however the early
      detection and prevention of subclinical myocardial damage has not been fully
      understood yet. Besides medical therapy regular physical activities may also play
      a role in the prevention and reduction of side effects of chemotherapy. The aim
      of our present study was to detect the effect of regular physical activities on
      the diastolic function and on the symptoms of late heart failure in case of
      anthracycline chemotherapy. The prospective study included 55 female patients
      (age 31-65 year, average 49.5 years) with breast cancer and no cardiovascular
      risk factors. Proper cardiologic checkup included physical examination (blood
      pressure, pulse, etc.), ECG, standard echocardiography parameters (EF, LV
      dimensions etc.) and specific tissue Doppler (TDI) measurements. Symptoms of
      heart failure were also recorded. After five years of follow-up, symptoms of
      heart failure were evaluated again. Patients were assigned into two groups
      depending on their physical activity: 36 patients did perform regular physical
      activities (mean age 49.2 years) and 19 patients did not (average age 50.1
      years). There was no significant difference between the two groups in basic
      physiological or standard echocardiography parameters neither at the baseline nor
      at the later time points. Diastolic dysfunction (decreased E/A) was detected 6
      months after the beginning of the treatment (T2 time point) in both groups. In
      the inactive group this value fell below one however there was no significant
      difference (1.1+/-0.25 vs. 0.95+/-0.22). One year after the beginning of the
      treatment (T3) a significant difference could be detected between the two groups
      (1.05+/-0.28 vs. 0.86+/-0.25. P=0.038). Consistent change in diastolic function
      (Ea/Aa) could be detected with the more sensitive TDI (Tissue Doppler Imaging)
      measurements after treatments in both groups, especially in the septal segment
      (in the non active group the Ea/Aa decreased markedly but not significantly at T2
      - 1.1+/-0.55 vs. 0.81+/-0.44, and this difference became significant at T3 and 2
      years after treatment (T4), p=0.007 and p=0.065). The filling pressure (E/Ea)
      rose above 10 (p=0.09) in the non active group at T2; and it kept rising in both
      groups and became significant at T3 (p=0.012). Five years after the onset of the
      treatment symptoms of heart failure were less frequently reported in the
      physically active group than in the inactive one (19.45% vs. 68.42%). The data of
      our study show that the diastolic dysfunction of the left ventricle related to
      the anthracycline therapy became evident in the physically active group later and
      the symptoms of heart failure were less frequent than in the non active group
      after five years period. Enrollment in sport activities could be a good means for
      partial prevention in this group of patients. Cardiologic checkup at proper
      intervals plays a pivotal role in detection of possible cardiotoxicity. This is a
      strong indication for changes in the lifestyle of the patient and the treatment
      protocol alike.

PMID- 27881010
TI  - Down-regulated expression of Tim-3 promotes invasion and metastasis of colorectal
      cancer cells.
AB  - To explore how Tim-3 is expressed and how its expression influences invasion and
      metastasis of colorectal cancer (CRC) cells. A total of 188 CRC patients were
      prospectively collected for this study. Meanwhile, 135 normal controls were
      incorporated during the same period. Intestinal samples of the CRC radical
      cancerous tissues, paracancerous tissues ( 5.0 cm beyond the cancer tissue) were
      collected for the following experiment. Furthermore, peripheral venous blood
      samples (10 ml) were collected from each subject. Immunohistochemical analysis,
      quantitative real-time polymerase chain reaction (RT-qPCR) and western blot were
      performed for the detection of Tim-3 in different tissues. The
      immunohistochemical staining results showed that a positive Tim-3 signal was
      localized in the cytoplasm and nucleus, observed as yellow or brown granules. Tim
      3 was largely expressed in colon carcinoma tissues and normal colon mucosa
      tissues but was rarely expressed in the cell membrane. RT-qPCR results indicated
      that Tim-3 mRNA levels were significantly lower in CRC tissues than in
      paracancerous tissues and normal colon mucosa tissues. A trend of decreased Tim-3
      mRNA levels was also found in the paracancerous tissues compared with the normal
      colon mucosa tissues (all P < 0.05). Western blot results revealed reduced Tim-3
      protein expression in CRC tissues compared with normal colon mucosa tissues and
      paracancerous tissues, and Tim-3 protein expression was much lower in the
      paracancerous tissues than in the normal colon mucosa tissues (all P < 0.05).
      Furthermore, obviously lower Tim-3 mRNA levels were found in the poorly
      differentiated CRC patients and in those with lymph node metastasis and distant
      metastasis (all P < 0.05). Collectively, Tim-3 expression was mainly located in
      the cytoplasm and nucleus, showing down-regulated expression in colon carcinoma
      tissues compared with normal and paracancerous tissues. Reduced Tim-3 expression
      may promote CRC invasion and metastasis providing a medical reference for the
      treatment of CRC.

PMID- 27881011
TI  - Adjuvant chemotherapy with bevacizumab (i.p.) can prolong survival time of
      patients with advanced ovarian cancer after cytoreduction.
AB  - Objective To assess whether adjuvant chemotherapy with bevacizumab
      intraperitoneal (i.p.) is better than adjuvant chemotherapy with bevacizumab
      intravenous (i.v.) or adjuvant chemotherapy only for patients with advanced
      ovarian cancer after cytoreduction. Selected patients with advanced ovarian
      cancer after cytoreduction were divided into three groups depend on their will:
      adjuvant chemotherapy only; adjuvant chemotherapy combined with bevacizumab
      intravenous (i.v.); adjuvant chemotherapy combined with bevacizumab
      intraperitoneal (i.p.). Patients in three groups were given 4-6 cycles of
      treatment and followed up for 3 years. posttreatment outcome, longterm survival
      and side effects were prospectively recorded and analyzed. Disease control rate
      (DCR) of three groups are 73.3%, 90.0%, 93.3% respectively (P<0.05). Remission
      rate (RR) and DCR of patients with bevacizumab intraperitoneal (i.p.) are better
      than that of patients with bevacizumab intravenous (i.v.) (P<0.05). The mean
      progression free survival (PFS) of patients with bevacizumab intraperitoneal
      (i.p.) (15.34 months) was longer than patients with bevacizumab intravenous
      (i.v.) (13.19 months), and both of two were longer than that of patients with
      adjuvant chemotherapy only (9.60 months) (chi2=52.11, P<0.001). The mean overall
      survival (OS) of patients with bevacizumab intraperitoneal (i.p.) (17.32 months)
      is longer than that of patients with adjuvant chemotherapy only (13.55 months)
      and patients with bevacizumab intravenous (i.v.) (15.17 months) (chi2=75.01,
      P<0.001). Incidence of hypertension and arrhythmia of groups with bevacizumab are
      higher than that of patients with adjuvant chemotherapy only (P<0.05). Standard
      chemotherapy combined with bevacizumab is reliable, safe and feasible for
      advanced ovarian cancer after cytoreduction without severe adverse effects.
      Bevacizumab intraperitoneal perfusion is better than that intravenous drip.

PMID- 27881012
TI  - Elevated aspartate aminotransferase and monocyte counts predict unfavorable
      prognosis in patients with malignant pleural mesothelioma.
AB  - Limited biomarkers predicting prognosis of malignant pleural mesothelioma (MPM)
      have been identified. The present study aims to assess potential laboratory
      prognostic factors of MPM. We retrospectively reviewed the clinical data of 105
      patients with MPM. The overall survival and prognostic factors were assessed by
      Kaplan-Meier curves and Cox regression analysis. A receiver operating
      characteristic (ROC) curve analysis was performed to determine the optimal cut
      off values. The mean age of the 105 patients (62 men, 43 women) was 56.0 years.
      The major clinical presentations were dyspnea, cough and chest pain. The most
      common laboratory abnormalities were thrombocytosis and elevated monocyte count.
      Significant prognostic factors on univariate analysis were performance status
      (PS), serum albumin, aspartate aminotransferase (AST), lactate dehydrogenase
      (LDH), alkaline phosphatase (ALP), monocyte, platelet to lymphocyte ratio (PLR),
      lymphocyte to monocyte ratio (LMR) and treatment strategy. Multivariate analysis
      showed PS, AST, monocyte, and treatment strategy were statistically significant
      (p<0.05). Higher AST level and monocyte count were both related to the presence
      of anemia (p=0.001 and 0.010, respectively) and higher ALP level (p=0.049 and
      0.001, respectively). A higher AST level was also associated with higher alanine
      aminotransferase (ALT) and LDH level (p<0.05). A higher monocyte count was also
      correlated with male patients, higher white blood cell (WBC), platelet,
      neutrophil counts, lower red blood cell (RBC) and LMR counts (p<0.05). In
      conclusion, our data show that PS<2, normal AST level, lower monocyte count, and
      multimodality treatment are independent positive prognostic factors of MPM. The
      elevated AST and monocyte levels represent unfavorable prognostic biomarkers of
      MPM.

PMID- 27881013
TI  - FEAT expression correlates with tumor size, PR status, HER2 expression, Ki67
      index, and molecular subtype and predicts recurrence in breast cancer.
AB  - FEAT protein is uniformly overexpressed in a variety of human cancers but weakly
      expressed in normal tissue. FEAT has antiapoptotic activity and plays a role in
      carcinogenesis; however, the correlation between FEAT and clinicopathologic
      characteristics in cancer has not been reported. Our study explores the
      expression of FEAT protein and its clinicopathologic significance in breast
      cancer. We examined the expression of FEAT in tissues from 131 cases of breast
      cancer by immunohistochemistry and analyzed the correlation between FEAT
      expression and clinicopathologic parameters. The difference in FEAT expression
      between normal breast tissues and breast cancer tissues was also investigated.
      Finally, we analyzed the association between FEAT expression and disease-free
      survival or overall survival. Our data showed that FEAT was expressed in the
      cytoplasm. The expression of FEAT protein was significantly higher in breast
      cancer tissues than in normal breast tissues. Moreover, the expression of FEAT
      protein was higher in breast cancer with a larger tumor size (>2 cm), negative
      PR, positive HER2, or higher Ki67 index (>=14%) than in breast cancer with a
      smaller tumor size (<=2 cm), positive PR, negative HER2, or lower Ki67 index
      (<14%) (P<0.05). In addition, the expression of FEAT protein was associated with
      tumor size, PR status, HER2 expression, Ki67 index, and molecular subtype.
      Survival analysis showed that disease-free survival and overall survival were
      significantly shorter in breast cancer patients with high FEAT expression than in
      those with low expression of FEAT (P<0.05). COX regression analysis showed that
      FEAT was an independent prognostic factor for recurrence in breast cancer, but
      not for survival. In conclusion, FEAT may be a potential biomarker for recurrence
      of breast cancer.

PMID- 27881014
TI  - Prognostic significance of number of lymph node metastasis on survival in
      patients with pathological T3 esophageal carcinoma.
AB  - The aim of this study was to evaluate the impact of the number of metastatic
      lymph nodes (MLN) and other risk factors on survival in patients with
      pathological T3 (pT3) esophageal carcinoma who were treated by esophagectomy. We
      analyzed 70 patients who received primary curative resection for pT3 esophageal
      cancer from 1997 to 2011. The prognostic role of age, gender, tumor location,
      cell type, pathological lymph node status (pN), number of MLNs (<3 vs >=3),
      metastatic lymph node ratio (MLR), type of resection, local recurrence, and
      distant metastasis on overall survival (OS) were examined by univariate and
      multivariate analyses. Survival curves were calculated using Kaplan-Meier method
      and survival differences were assessed by log-rank test. A receiver operating
      characteristic analysis was used to determine the optimum cut-off point for the
      MLR. The median follow-up time was 42 (range, 8-128) months, and the 1-, 3- and 5
      year OS rates were 78.6%, 38.1%, and 22.5%, respectively. Tumor location, pN, the
      number of MLNs, local recurrence, and distant metastasis had a significant effect
      on OS in the univariate analysis. In the multivariate model, the number of MLNs
      (p=0.02; hazard ratio (HR), 2.1; 95% confidence interval (CI), 1.1-4.1) and
      distant metastasis (p=0.007; HR, 5.1; 95% CI, 1.5-16.8) were independent risk
      factors for OS. Patients with pT3 esophageal cancer who have 3 or more MLNs and
      distant metastasis have a poor OS, and this result can be used as a factor for
      better estimation of prognosis.

PMID- 27881015
TI  - Predictors of survival in patients with brain metastases from gastric cancer.
AB  - This study aims to identify predictors of survival and contribute to treatment
      personalization in patients with brain metastases from gastric cancer. Twelve
      patients received whole-brain radiotherapy (WBRT), four stereotactic radiosurgery
      and six neurosurgery plus WBRT. Treatment regimen, age, gender, Eastern
      Cooperative Oncology Group (ECOG) performance score, tumor site, number of brain
      metastases, extra-cranial metastases and interval between cancer diagnosis and
      brain metastases were evaluated for survival. On univariate analyses, more
      intensive treatment (p=0.003), ECOG-score 0-1 (p<0.001), cardiac location
      (p=0.025) and single brain metastasis (p=0.023) were associated with better
      survival. On multivariate analysis, ECOG-score maintained significance (p<0.001).
      Patients with all three positive factors on univariate analysis had a 12-month
      survival rate of 100%, patients with three negative factors a 3-month survival
      rate of 0%. Predictors of survival were identified that can guide physicians
      selecting personalized treatment approaches for patients with brain metastases
      from gastric cancer.

PMID- 27881016
TI  - Platelet count and mean platelet volume are associated with not only bone, soft
      tissue, and lymph node metastases but also with malignant pleural effusion in
      lung cancer patients.
AB  - An increased platelet count is often observed in lung cancer patients. Whether
      and how the platelets affect cancer progression have yet to be established. The
      aim of the study was to investigate the involvement of the platelet count and
      mean platelet volume (MPV) in the prognosis and progression of lung cancer
      patients. This retrospective study included 146 patients with newly diagnosed
      primary lung cancer. The platelet count and MPV were measured before invasive
      diagnostic procedures and treatment. These platelet indices, overall survival of
      the patients, and tumor metastases for each organ were analyzed. On Kaplan-Meier
      survival analysis, the overall survivals of patients with platelet counts <=
      244.0 * 109/L or MPV > 9.7 fL were longer than those of patients with platelet
      counts > 244.0 * 109/L or MPV <= 9.7 fL. Cox regression analysis showed that poor
      performance status, increased platelet count, and increased C-reactive protein
      were independent prognostic factors. The platelet indices were associated with
      metastases to bone, soft tissue, and lymph node, in addition to malignant pleural
      effusion. Increased platelet count and decreased MPV were unfavorable prognostic
      factors for patients with lung cancer, and they were involved in bone, soft
      tissue, and lymph node metastases and malignant pleural effusion.

PMID- 27881017
TI  - Association between interleukin-18 variants and prostate cancer in Slovak
      population.
AB  - Interleukin-18 (IL-18), pro-inflammatory cytokine, plays important role in
      antitumor immunity. Polymorphisms in the IL-18 gene may lead to its altered
      production/activity and such modulate susceptibility to prostate cancer. The aim
      of this study was to evaluate the relationship between the -607 and +105
      polymorphisms in the IL-18 gene and the risk of prostate cancer development and
      progression in Slovak population. The study was performed using 425 patients with
      prostate cancer, 270 patients with benign prostatic hyperplasia (BHP) and 263
      healthy male controls. The statistically significant association of the -607 AC
      genotype (OR = 2.24; p < 0.001), CC genotype (OR = 1.86; p = 0.006), as well as C
      allele (OR = 1.27; p = 0.033) with the higher risk of prostate cancer development
      was observed. No association of the IL-18 -607 polymorphism and BHP was detected.
      The subset analysis revealed the significant association of the -607 AC genotype
      (OR = 2.01; p = 0.008) with development of higher-grade carcinomas (Gleason score
      >=7) and the strong association of the -607 AC genotype (OR = 3.11; p < 0.001),
      CC genotype (OR = 2.96; p < 0.001) as well as C allele (OR = 1.51; p = 0.003)
      with the higher risk of prostate cancer development in the group of patients with
      PSA < 10 ng/ml. The -607 AC genotype was also connected with significantly higher
      IL-18 plasma concentrations. No association between the IL-18 +105 polymorphism
      and prostate cancer was observed. The analysis of the distribution of the -607
      and +105 haplotypes showed significant association of the - 607 C/ + 105 A and -
      607 C/ + 105 C haplotypes with the risk of prostate cancer. This study found that
      the IL-18 -607 promoter polymorphism could contribute to prostate cancer
      development in Slovak population. Its presence was also associated with
      development of higher-grade carcinomas and therefore may influences the prognosis
      and aggressiveness of the disease.

PMID- 27881018
TI  - A different prognostic value of BRAFV600E mutation positivity in various age
      groups of patients with papillary thyroid cancer.
AB  - The aim of the retrospective single-center study was to assess the prognostic
      value of BRAFV600E mutation positivity (BRAFV600E+) on disease
      persistence/recurrence in patients with papillary thyroid cancer (PTC). A total
      of 199 patients having had initial surgery with neck dissection in our hospital
      between 6/2009-6/2012 were included in the cohort. Excluded were patients with
      unifocal microcarcinoma <=1cm. BRAFV600E mutation was tested from formalin-fixed
      paraffin-embedded surgicaly removed tumors. All included patients were
      postoperatively treated with radioiodine. The median duration of follow-up was 43
      months, quartiles range 30 - 58 months. Variables included in the final model:
      BRAFV600E+, categorised age, sex, and high-risk status, or alternatively lymph
      node status. Based on differences in persistence/recurrence rates, patients were
      divided into three age categories (<35, 35-60, >=60). Multiple regression
      analysis showed a significant interaction between BRAFV600E+ and age, modifying
      the effect of BRAFV600E+ on persistence/recurrence. BRAFV600E+ in low-risk
      patients of any age and in high-risk middle-aged patients did not confer
      additional hazard compared with BRAFV600E mutation negative (BRAFV600E-) low-risk
      and BRAFV600E- high-risk patients, respectively. However, younger (<35 years) and
      older (>=60 years) high-risk BRAFV600E+ patients had 17.28 and 33.49-fold
      increased hazard of persistence/recurrence, respectively, compared with low-risk
      BRAFV600E- patients. The alternative model including lymph node status yielded
      similar results for the prognostic significance of BRAFV600E+ in younger and
      older patients. In conclusion, the prognostic value of BRAFV600E+ depends on high
      risk status and likely on age-associated factors. Such additional knowledge could
      change clinical decision-making in treatment modality.

PMID- 27881019
TI  - Comparative Analysis of Renal Functional Outcomes and Overall Survival of Elderly
      vs Nonelderly Patients Undergoing Radical Nephrectomy.
AB  - PURPOSE: To evaluate changes in renal function and overall survival in elderly vs
      nonelderly patients undergoing radical nephrectomy (RN) for renal masses.
      PATIENTS AND METHODS: We reviewed available records of 392 patients undergoing RN
      from 2008 through 2013. Patients were divided into elderly, defined as >=70 years
      old (n = 110), or nonelderly (n = 282) at the time of nephrectomy. The groups
      were compared for perioperative characteristics, renal functional outcomes, and
      overall survival. Standard Student's t-tests were used for continuous variables
      and Fischer's exact tests for categorical comparisons. Kaplan-Meier estimate
      models for survival were compared using log-rank tests. RESULTS: Elderly patients
      were more likely to have comorbidities. Preoperative estimated glomerular
      filtration rate (GFR) of elderly patients was significantly lower (65.6 vs 77.9
      mL/minute/1.73 m2, p = 0.0002), as was GFR at discharge (47.7 vs 57.2
      mL/minute/1.73 m2, p = 0.001) and at maximum follow-up (46.8 vs 57.4
      mL/minute/1.73 m2, p = 0.001). Of the patients with GFR >60 before surgery, de
      novo CKD stage III progression (defined as GFR <60) was detected in 74% of
      elderly and 53% nonelderly (odds ratio 2.47; 95% confidence interval 1.25-4.88; p
      = 0.01). Overall survival was not statistically different. When stratified for
      elderly and preoperative GFR <60, overall survival curves were not statistical
      different (log-rank test, p = 0.23). CONCLUSIONS: Elderly patients who undergo RN
      have worse renal functional outcomes. Following nephrectomy, these patients are
      at higher risk of CKD progression than nonelderly patients. However, there does
      not appear to be a difference in overall survival between cohorts, even when
      stratified for preoperative GFR <60. These findings should be considered during
      preoperative decision-making.

PMID- 27881021
TI  - Corrigendum.

PMID- 27881020
TI  - Cardiac function during resuscitation from hemorrhagic shock with polymerized
      bovine hemoglobin-based oxygen therapeutic.
AB  - Hemorrhage impairs myocardial contractile function and decreases oxygen delivery.
      This study investigates how polymerized bovine hemoglobin (PolyHb) solutions
      affect cardiac function after resuscitation from hemorrhagic shock (HS). Hamsters
      were hemorrhaged and resuscitated with PolyHb at 8.5 g/dL and 11.5 g/dL. Left
      ventricle (LV) function was assessed during shock and resuscitation using a
      miniaturize conductance catheter. PolyHb resuscitation had no beneficial effects
      in cardiac function; it increased cardiac afterload and systemic vascular
      resistance (SVR) of 46 and 116% for 8.5 and 11.5 g/dL, respectively. Study
      findings indicate that preclinical evaluation of cardiac function is essential to
      develop safe and efficacious alternatives to blood transfusion.

PMID- 27881022
TI  - Elevated serum YKL-40 levels in patients with Kawasaki disease.
AB  - CONTEXT: YKL-40 is an inflammatory biomarker for endothelial dysfunction that may
      have a role in Kawasaki disease (KD). OBJECTIVES: We investigated the association
      of serum YKL-40 levels with KD and established laboratory parameters for YKL-40
      levels and other inflammatory markers. METHODS: YKL-40 levels and other
      inflammatory markers of 23 KD patients, 9 disease control patients and 11 age
      matched healthy controls. RESULTS: YKL-40 concentration in the serum of KD
      patients significantly increased during the acute disease phase compared with
      those of disease controls and healthy controls. CONCLUSIONS: Increased YKL-40
      levels may provide a useful inflammatory marker for patients with KD.

PMID- 27881023
TI  - Impaired gallbladder function in patients after total gastrectomy.
AB  - BACKGROUND AND AIMS: The incidence of gallstones and gallbladder sludge is higher
      in patients after total gastrectomy than in general population. Formation of
      gallstones after gastrectomy is multifactorial. Here, we investigate the changes
      in gallbladder and biliary tract functions by cholescintygraphy and monitored
      changes in cholecystokinin (CCK) release in long-term survivors after total
      gastrectomy for gastric carcinoma. MATERIAL AND METHODS: Patients had undergone
      total gastrectomy for gastric carcinoma at least five years ago. The final study
      population consisted of 25 patients. RESULTS: Eight patients had undergone
      cholecystectomy before or at the time of gastrectomy. Gallstone formation was
      observed in seven of the remaining 17 patients during follow-up (41%). Maximum
      uptake of radioactivity and gallbladder maximum uptake was significantly delayed
      in the gastrectomy group than in the control group. There was no significant
      difference in CCK levels after the overnight fasting and at 60 minutes after
      stimulation among patients with or without stones in situ compared with healthy
      volunteers, but 30 minutes after the energy-rich drink patients had higher CCK
      levels than the control group. CONCLUSIONS: In gastrectomy patients, technetium
      isotope visualisation of the gallbladder and time for maximum activity was
      significantly delayed. This may indicate impaired gallbladder function. On the
      contrary, CCK release was not impaired.

PMID- 27881025
TI  - Autophagy-related protein 7 level in patients with ulcerative colitis.

PMID- 27881024
TI  - The use of atorvastatin for chronic subdural haematoma: a retrospective cohort
      comparison study.
AB  - Chronic subdural haematoma (CSDH) is a common neurosurgical condition. Burr-hole
      for drainage is an effective treatment. However, recurrence can be up to 8-33%
      and is associated with morbidities and mortalities. The underlying pathogenesis
      was postulated to be localised inflammation and pathological aberrant vessels
      formation. Atorvastatin, an HMG-CoA reductase inhibitor, is a type of lipid
      lowering medication. In animal studies and a preliminary clinical trial,
      Atorvastatin was shown to be effective in the treatment of CSDH. It was found to
      inhibit inflammation and promote vascular maturation at the neomembrane of CSDH.
      Our study aimed to investigate the efficacy of Atorvastatin in CSDH. During the
      study period from January to December 2014, Atorvastatin was used in 12 CSDH
      patients with Glasgow Coma Scale (GCS) 13-15 or Markwalder's Grading Scale (MGS)
      Grade 0-2. They were retrospectively compared with GCS- and MGS-matched controls
      who had not used statin. Improvement with haematoma resolution at 3 months was
      75% (9/12) for the Atorvastatin group, versus 42% (5/12) for the Control group (p
      = 0.0977). The risk of deterioration requiring burr-hole drainage was 16.7%
      (2/12) in the Atorvastatin group, versus 58.3% (7/12) in the Control group (p =
      0.0447). The Odds Ratio (OR) of deterioration requiring burr-hole drainage with
      Atorvastatin was 0.143 (95%CI: 0.021-0.958), which favours the use of
      Atorvastatin in CSDH (p = 0.0451). The Number needed to treat (NNT) was 2.4 (p =
      0.0447; 95%CI: 1.31-14.93). In conclusion, this retrospective cohort comparison
      study has shown that CSDH with Atorvastatin had a lower rate of deterioration and
      burr-hole drainage.

PMID- 27881026
TI  - Cholecystokinoma syndrome and diarrhea.

PMID- 27881028
TI  - Corrigendum.

PMID- 27881027
TI  - Is Robotic Partial Nephrectomy Safe for T3a Renal Cell Carcinoma? Experience of a
      High-Volume Center.
AB  - PURPOSE: To compare the oncological and functional outcomes of robotic partial
      nephrectomy (RPN) with radical nephrectomy (RN) in renal-cell carcinoma (RCC)
      cases with pT3a staging. PATIENTS AND METHODS: A retrospective analysis of our
      IRB-approved nephrectomy database from 2005 to 2015 was performed. RPN and RN
      cases with confirmed RCC and pT3a staging were matched. Preoperative variables,
      functional, and oncological outcomes were compared between the groups, as well as
      Kaplan-Meier estimated overall survival (OS), cancer-specific survival (CSS), and
      recurrence-free survival (RFS). A multivariable Cox proportional hazards
      regression model for overall mortality rate was generated to evaluate hazard
      ratios (HRs) of potential risk factors. RESULTS: Seventy patients with pT3a
      tumors composed each group. Preoperative variables were comparable between
      groups. The median follow-up time for the cohort was 20 (9-38) months and the
      renal function preservation was higher in the RPN group (86% vs 70%; p < 0.001).
      The estimated 3 years of OS (90% vs 84%; p = 0.42), CSS (94% vs 95%; p = 0.78),
      and RFS (95% vs. 100%; p = 0.06) were similar between RPN and RN groups,
      respectively. On multivariable Cox regression model, the presence of >=2
      aggressive tumor features was the only factor associated with increased risk of
      overall mortality rate (HR 4.01 95% confidence interval [1.13, 14.27)]; p =
      0.03). CONCLUSION: Patients with localized pT3a RCC treated with RPN had similar
      short-term oncological and better renal functional outcomes compared with similar
      cases treated by RN. In the minimally invasive robotic surgery era, renal masses
      suspicious for pathological T3a disease should not be a deterring factor for
      performing nephron-sparing surgery when technically feasible by skilled surgeons.

PMID- 27881029
TI  - Pemphigus herpetiformis-type drug reaction caused by erdosteine containing
      mucolytic in a child.
AB  - Drug-related pemphigus is very rare in children. Erdosteine is a thiol compound
      having mucoactive, antioxidant, anti-inflammatory, and antitussive effects and is
      reported to be safe for treatment of acute respiratory tract diseases in
      children. Herein, we report a 9-year-old boy presented with pemphigus
      herpetiformis associated with anti-desmoglein 1 antibodies due to erdosteine
      consumption.

PMID- 27881031
TI  - Cavitation enhances coagulated size during pulsed high-intensity focussed
      ultrasound ablation in an isolated liver perfusion system.
AB  - PURPOSE: To investigate whether cavitation enhances the degree of coagulation
      during pulsed high-intensity focussed ultrasound (HIFU) in an isolated liver
      perfusion system. METHODS: Isolated liver was treated by pulsed HIFU or
      continuous-wave HIFU with different portal vein flow rates. The cavitation
      emission during exposure was recorded, and real-time ultrasound images were used
      to observe changes in the grey scale. The coagulation size was measured and
      calculated. RESULTS: HIFU treatment led to complete coagulation necrosis and
      total cell destruction in the target regions. Compared to exposure at a duty
      cycle (DC) of 100%, the mean volumes of lesions induced by 6 s exposure at DCs of
      50% and 10% were significantly larger (P < .01) but were smaller at a DC of 5%.
      The necrosis volume was negatively related to the perfusion rate in the pulsed
      HIFU at a DC of 50% for exposure durations of 4 and 6 s, while the perfusion flow
      rate did not affect the necrosis volume for exposure durations of 1, 2 and 3 s.
      For increased perfusion flow rates, there was no significant decrease in the
      cavitation activity for the pulsed-HIFU (P > .05). For continuous-wave HIFU
      exposure, there was a significant decrease in the necrosis volume and cavitation
      activity for exposure times of 1, 2, 3, 4, and 6 s with increasing portal
      perfusion rates. CONCLUSION: Perfusion flow rates negatively influence cavitation
      activity and coagulation volume. Ablation is significantly enhanced during pulsed
      HIFU exposure compared with continuous-wave HIFU.

PMID- 27881030
TI  - The effect of tumor necrosis factor inhibitor therapy on the incidence of
      myocardial infarction in patients with psoriasis: a retrospective study.
AB  - BACKGROUND: Psoriasis has been shown to be associated with increased incidence of
      myocardial infarction (MI). The data on the effect of tumor necrosis factor (TNF)
      inhibitors on MI in psoriasis are scarce. OBJECTIVE: To evaluate the effect of
      TNF inhibitors on the risk of MI in psoriasis patients compared with methotrexate
      (MTX) and topical agents. METHODS: Data were obtained from the Electronic Health
      Records database of Farwaniya Hospital from psoriasis patients seen from January
      2008 to December 2014. Patients were categorized into TNF inhibitor, MTX and
      topical cohorts. RESULTS: The study included 4762 psoriasis patients. Both TNF
      inhibitor and MTX cohorts showed a statistically lower rate of MI compared with
      topical cohort. However, there was no statistically significant difference in MI
      rate between TNF inhibitor and MTX cohorts (P = .32). The probability of MI was
      lower in TNF inhibitor responders compared with non-responders (p = .001).
      CONCLUSIONS: The use of TNF inhibitors in psoriasis showed a significant
      reduction in the risk of MI compared with topical agents and a non-significant
      reduction compared with MTX. Responders to TNF inhibitor therapy showed a
      reduction in MI rate compared with non-responders.

PMID- 27881032
TI  - Clinical implications of assay specific differences in f-calprotectin when
      monitoring inflammatory bowel disease activity over time.
AB  - OBJECTIVE: With several faecal calprotectin (FC) assays on the market, it has
      been difficult to define a uniform threshold for discriminating between remission
      and active disease in patients with inflammatory bowel disease (IBD). We aimed to
      compare the results of different FC-assays in IBD patients, followed over time.
      MATERIAL AND METHODS: IBD patients provided faecal samples and reported clinical
      activity every third month prospectively over a two year period. FC was measured
      with two ELISA - (Buhlmann and Immunodiagnostik) and one automated
      fluoroimmunoassay (Phadia). RESULTS: In total, 13 patients provided 91 faecal
      samples. The median (IQR) concentration of FC was higher at active disease than
      at remission for all assays: Buhlmann 845 (1061-226) MUg/g versus 62 (224-39)
      MUg/g, Phadia 369 (975-122) MUg/g versus 11 (52-11) MUg/g, and Immundiagnostik
      135 (302-69) MUg/g versus 8 (56-4) MUg/g. The Buhlmann assay produced the largest
      absolute difference but the corresponding relative difference seemed to be more
      pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or
      the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the
      Buhlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the
      specificity for discriminating active disease from remission varied between
      assays (34-75%) when the cut-off 50 MUg/g was used, whereas the differences in
      sensitivity were less pronounced. CONCLUSIONS: Cross-comparisons revealed overall
      poor agreement between the assays as well as differences in the dynamics of FC.
      These findings suggest that standardisation of the method is needed to implement
      FC as a disease monitoring tool at large-scale.

PMID- 27881033
TI  - Early diabetes screening in obese women.
AB  - OBJECTIVE: To describe maternal characteristics related to early screening for
      diabetes in obese women and evaluate the benefits of early diabetes screening and
      diagnosis. STUDY DESIGN: Retrospective cohort of obese women (BMI >=30 kg/m2)
      without pregestational diabetes who delivered a singleton gestation between 2011
      and 2012. Maternal characteristics/demographics and maternal and neonatal
      outcomes were compared between women with early diabetes screening (<20 weeks)
      versus traditional screening. We additionally compared maternal and neonatal
      outcomes for women with an early versus traditional diabetes diagnosis. RESULTS:
      Of the 504 eligible women, 135 (26.8%) had early diabetes screening. Obese women
      with early screening were older, had a higher BMI, were more likely to have
      hypertension and neonates admitted to the NICU. Of women with early screening, 31
      (23%) were diagnosed early. Women with an early diagnosis of diabetes were more
      likely to require treatment with insulin (36% vs. 23%, p = 0.003). Women with an
      early diagnosis of diabetes were more likely to have neonates in the NICU (48%
      vs. 26%, p = 0.03). CONCLUSIONS: Early screening for diabetes was more common in
      older women with additional comorbidities. Obese women diagnosed via early
      screening were more likely to require medical treatment for diabetes, suggesting
      a value to early screening.

PMID- 27881034
TI  - Galanin in pregnancy: Is there an association with birth weight and gestational
      diabetes?
AB  - OBJECTIVE: To review the actions of galanin during pregnancy and to examine the
      existence of an association between galanin and birthweight as well as with
      gestational diabetes mellitus (GDM). RESULTS: Galanin concentrations in maternal
      circulation are similar in pregnant and nonpregnant status and have been
      correlated with body mass index (BMI). There is evidence of an association
      between birthweight and galanin concentrations in amniotic fluid during second
      trimester and galanin concentrations in umbilical cord at term. Moreover, there
      is a positive correlation between maternal galanin concentrations and existence
      of GDM. However, galanin concentrations in fetal circulation have not been
      correlated with neonatal fat mass. Neonatal galanin concentrations do not differ
      among uncomplicated pregnancies and those complicated by GDM or intrauterine
      growth retardation (IUGR). CONCLUSIONS: There is evidence for an association
      between galanin during pregnancy with birth weight and metabolic processes.
      Further studies are required in order to elucidate this role. Galanin could serve
      as a predictor of neonatal body weight, alternations of which contribute to the
      development of diseases during adulthood.

PMID- 27881035
TI  - The dangers of the bread clip - CT imaging and management: a case report.
AB  - Most ingested foreign objects pass the gastrointestinal tract without serious
      consequences. A particular foreign object has been described related to serious
      adverse events such as gastrointestinal bleeding and small bowel obstruction: a
      plastic bread clip. During the diagnostic phase the morphology of this item is
      not always recognized during ultrasonography or CT imaging. In this case report
      we describe the diagnosis and management of a patient with a small bowel
      perforation caused by ingestion of a bread clip.

PMID- 27881037
TI  - A Novel Gel Pad Laryngeal Ultrasound for Vocal Cord Evaluation.
AB  - BACKGROUND: Laryngeal ultrasound (LUS) is a new method for vocal cord evaluation
      in patients with risk of vocal cord palsy (VCP). However, the previously
      described LUS reportedly had a high failure rate of vocal cord visualization in
      male patients. A novel gel pad LUS was devised to overcome the limitations of the
      previous method. METHODS: A total of 482 (100 male) consecutive LUS and direct
      laryngoscopy examinations were performed in thyroidectomy and other neck surgery
      patients. The conventional LUS and gel pad LUS were used for all patients.
      Findings were independently cross-validated with direct laryngoscopy. RESULTS:
      The conventional LUS and gel pad LUS methods had a 93.4% and 99.0% visualization
      rate, respectively, with a sensitivity of 98.0% for both methods, and a
      specificity of 99.7% and 99.8%, respectively. Among the 482 patients, 51 patients
      had VCP and 91 patients had diffuse thyroid cartilage calcification interrupting
      LUS. CONCLUSION: The new gel pad LUS method significantly enhances the
      visualization of vocal cords in patients who have diffuse thyroid cartilage
      calcification interrupting LUS and, therefore, the overall efficacy of LUS as a
      perioperative diagnostic tool for VCP.

PMID- 27881036
TI  - Comparative proteomics analysis of spermary and ovary in Hyriopsis schlegelii.
AB  - We provide the first large-scale quantitative proteomics analysis in Hyriopsis
      schlegelii. To investigate the proteins expressed in the gonads, a quantitative
      proteomics approach has been utilized to analyze differentially expressed
      proteins between the spermary and ovary. In this study, we identified and
      quantified 2416 proteins in the gonads of Hyriopsis schlegelii. Of these, 559
      proteins showed significantly different expression between the spermary and
      ovary. Some specific proteins expressed in either the spermary or ovary were
      identified in Hyriopsis schlegelii. In addition, a series of proteins related to
      gametogenesis were also identified. Compared with previous reports, many proteins
      in Hyriopsis schlegelii identified here have different expression patterns
      between the spermary and ovary. The special hermaphroditism in Hyriopsis
      schlegelii may contribute to these inconsistent results. The provided proteomics
      data could be considered as a starting point for subsequent studies focusing on
      the proteins involved in sexual gland development and maturity.

PMID- 27881038
TI  - 'Enhance her pleasure - and your grip strength': Men's Health magazine and pseudo
      reciprocal pleasure.
AB  - This paper provides a snapshot of the Top Ten free, digital Men's Health magazine
      articles, accessed on a randomly selected day, that can be viewed as a
      collection; both a product for readership consumption and a construct of
      readership priorities. Through close textual analysis, we examine how discourses
      about masculinity, heterosex and consumerism have intersected to create a model
      of masculinity based on the discipline of male pleasure, which impacts on men's
      approach to female pleasure and gender dynamics. The analysis contributes to the
      developing research about the sexual and bodily discourses the magazine promotes
      and identifies a model of masculinity where men can 'have their cake and eat it';
      seeming to adhere to ideals of gender equality and reciprocity while retaining
      their traditional patriarchal position of producer/provider. They are encouraged
      to do so by approaching female orgasm as a product, which they can 'purchase'
      through adhering to Men's Health magazine's sexual advice and bodily labour at
      control, delay and discipline of their own pleasure and orgasm. We argue that
      this approach to sex disenfranchises men, and in turn their partners, of
      opportunities to access alternative models of embodied pleasure.

PMID- 27881039
TI  - Fludarabine, cyclophosphamide and lenalidomide in patients with
      relapsed/refractory chronic lymphocytic leukemia. A multicenter phase I-II GIMEMA
      trial.
AB  - The activity and safety of a regimen combining lenalidomide with fludarabine and
      cyclophosphamide (FC) was investigated in patients with relapsed/refractory (R/R)
      chronic lymphocytic leukemia (CLL). Treatment consisted of six monthly courses of
      the FC regimen combined with 14 days of lenalidomide given at the starting dose
      of 2.5 mg during course 1. The maximum tolerated dose of lenalidomide was 5 mg.
      Forty patients were assessed for response, 66% were IGHV unmutated, 45% showed
      deletion 11q or 17p. The overall response and complete remission rates were 62.5%
      and 22.5%, respectively, the median progression-free and overall survival (OS)
      were 19 and 45 months, respectively. Grade 3-4 granulocytopenia was observed in
      65% of cases, severe infections in 7.5%, the lenalidomide-related toxicity was
      mild. In conclusion, the results of this study demonstrate that low-dose
      lenalidomide associated with the FC schedule is an effective treatment for R/R
      patients with CLL, associated with an acceptable safety profile.

PMID- 27881040
TI  - A Single Dose of Docosahexaenoic Acid Increases the Functional Recovery Promoted
      by Rehabilitation after Cervical Spinal Cord Injury in the Rat.
AB  - Task-specific rehabilitation has been shown to promote functional recovery after
      acute spinal cord injury (SCI). Recently, the omega-3 polyunsaturated fatty acid,
      docosahexaenoic acid (DHA), has been shown to promote neuroplasticity after SCI.
      Here, we investigated whether the combination of a single bolus of DHA with
      rehabilitation can enhance the effect of DHA or rehabilitation therapy in adult
      injured spinal cord. We found enhanced functional improvement with DHA in
      combination with rehabilitation compared with either treatment alone in a rat
      cervical lateral hemisection SCI model. This behavioral improvement correlated
      with a significant sprouting of uninjured corticospinal and serotonergic fibers.
      We also observed that the greatest increase in the synaptic vesicle protein,
      synaptophysin, and the synaptic active zone protein, Bassoon, occurred in animals
      that received both DHA and rehabilitation. In summary, the functional,
      anatomical, and synaptic plasticity induced by task-specific rehabilitation can
      be further enhanced by DHA treatment. This study shows the potential beneficial
      effects of DHA combined with rehabilitation for the treatment of patients with
      SCI.

PMID- 27881041
TI  - Incidence and survival outcomes of chronic myelomonocytic leukemia in the United
      States.
AB  - Chronic myelomonocytic leukemia (CMML) is an aggressive neoplasm with sparse data
      on outcomes at a population level. Using Surveillance Epidemiology and End
      Results (SEER) database, we identified 2238 patients with CMML diagnosed in the
      period 2003-2013. We found that the disease incidence was significantly higher
      with advancing age and lower in females, Blacks, and Asian/pacific islanders.
      Median OS declined significantly with increasing age (age 20-39 - 25 months, age
      40-59 - 20 months, age 60-79 - 18 months, and age >=80 - 11 months, p < .01), but
      did not vary by gender or race. Median OS has improved in the period 2007-2013 as
      compared with 2003-2006 (17 months vs. 14 months, p < .01). In spite of advances
      in CMML biology and therapeutics, in general, the survival of CMML patients
      remains dismal. More effective therapies are needed to improve the outcomes of
      CMML.

PMID- 27881042
TI  - Correlation between spheno-occipital synchondrosis, dental age, chronological age
      and cervical vertebrae maturation in Turkish population: is there a link?
AB  - OBJECTIVE: To assess the correlation between third molar mineralization (TMM),
      spheno-occipital synchondrosis (SOS) fusion, chronologic age and cervical
      vertebrae maturation (CVM) for skeletal maturation. MATERIALS AND METHODS:
      Radiographs for 116 patients between 8 and 28 years were evaluated for age
      determination using mandibular TMM, SOS fusion and CVM. Spearman Correlation and
      Kappa test analyses were used to assess the relationship between variables and
      for intraobserver reliability. RESULTS: Strong correlation was found between
      chronological age and TMM for males (r = .802) and females (r = .842), very
      strong correlation was found between age and CVM for males (r = .812) and
      moderate for females (r = .449), it was strong between age and SOS fusion for
      males (r = .810) and females (r = .643). Correlation between TMM and SOS was
      found to be strong for males (r = .759) and moderate for females (r = .534), it
      was strong between TMM and CVM for males (r = .723) and weak for females (r =
      .371). Very strong correlation was found between CVM and SOS fusion for males (r
      = .851) and strong correlation for females (r = .618). CONCLUSION: Good
      correlation was found between the degrees of TMM, fusion of SOS and CVM in young
      Turkish population.

PMID- 27881043
TI  - Experimental research methods in orthopedics and trauma.

PMID- 27881045
TI  - Exploring unobserved heterogeneity in perinatal and neonatal mortality risks: The
      case of an Italian sharecropping community, 1900-39.
AB  - Previous researchers have found that traditional determinants explain only a
      limited part of the variation in perinatal and infant mortality at the family
      level. In the study reported in this paper, we explored the factors that make the
      perinatal/neonatal death risk more heterogeneous across families. We estimated
      logistic regressions with cluster random effects at the maternal level, using
      data from the Italian village of Granarolo from 1900 to 1939. We estimated the
      effects of selected predictors on perinatal/neonatal mortality and unexplained
      inter-family variation. We found that non-rural skilled and lower-skilled workers
      experienced higher perinatal and neonatal mortality risks. Unexplained
      heterogeneity at the maternal level was lower for women living in sharecropper
      families than for those in landless labourer and non-rural worker families.
      Unexplained perinatal and neonatal mortality components were also due to socio
      economic differences and were not necessarily related only to maternal biological
      features or shared genetic frailty.

PMID- 27881044
TI  - Promoting physical activity in hospitalized patients with mild ischemic stroke: a
      pilot study.
AB  - BACKGROUND: Patients with acute stroke spend most of their hospital day inactive.
      However, a method to promote physical activity (PA) in stroke has not been
      established. OBJECTIVE: To evaluate the effectiveness of promoting PA by
      enhancing self-efficacy in hospitalized patients with mild ischemic stroke.
      DESIGN: Pre-post interventional study. METHODS: Hospitalized patients with mild
      ischemic stroke who could walk without assistance were recruited. We measured the
      daily number of steps taken as the index of daily hospitalized PA using an
      accelerometer. At the baseline measurement, patients did not receive
      accelerometer-based feedback. To promote hospitalized PA, a physical therapist
      provided instruction on the self-monitoring approach and discussed PA targets,
      encouraged the patients to walk more, and instructed them on the importance of PA
      after stroke. We also measured self-efficacy for PA using an assessment tool at
      the baseline and during the intervention. RESULTS: Twenty-two patients (62.5
      years old, 68.2% men) were included. PA during the intervention was higher than
      that at the baseline measurement (5709.4 +/- 2236.1 vs. 2813.9 +/- 1511.9
      steps/day, p < 0.001). Self-efficacy for PA during the intervention was also
      higher than that at the baseline measurement (76.4 +/- 18.8 vs. 58.9 +/- 29.0
      points, p < 0.001). CONCLUSIONS: Promoting PA by enhancing self-efficacy may
      increase PA and self-efficacy for PA in hospitalized patients with mild ischemic
      stroke. The present results might provide new strategies of PA promotion in these
      hospitalized patients.

PMID- 27881046
TI  - Preparation and characterization of bee venom-loaded PLGA particles for sustained
      release.
AB  - Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by
      double emulsion-solvent evaporation, and characterized for a sustained-release
      system. Factors such as the type of organic solvent, the amount of bee venom and
      PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification
      method were considered. Physicochemical properties, including the encapsulation
      efficiency, drug loading, particle size, zeta-potential and surface morphology
      were examined by Fourier transform infrared (FT-IR) spectroscopy, differential
      scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee
      venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta
      potentials of the bee venom-loaded PLGA particles were negative owing to the
      PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated
      in the PLGA particles, indicated by the disappearance of the amine and amide
      peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA
      particles was intact. In vitro release of the bee venom from the bee venom-loaded
      PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded
      PLGA particles can help improve patients' quality of life by reducing the number
      of injections required.

PMID- 27881047
TI  - Cambodian boys' transitions into young adulthood: exploring the influence of
      societal and masculinity norms on young men's health.
AB  - A growing body of evidence focuses on the experiences of young men in low-income
      countries, including their health vulnerabilities. Much of this research has been
      conducted in sub-Saharan Africa, Asia and Latin America. Limited evidence exists
      on the norms influencing boys' transitions into young adulthood in Southeast
      Asia, and in Cambodia in particular. To help fill this gap, we conducted a
      comparative case study using participatory methods with 16-19-year-old young men
      in rural and urban Cambodia, and with the adults who intersect in their lives.
      Findings suggest that in line with their counterparts growing up elsewhere,
      Cambodian boys welcome becoming young men as a time of newly acquired adult roles
      and responsibilities, while some may experience growing up as a time of bodily
      change, burgeoning sexual feelings and limited sources of support and guidance.
      As a result, some may strive more intensely to conform to the alcohol use and
      violence modelled by the older men in their environments. Additional research is
      needed to better understand the vulnerabilities of boys' transition into young
      adulthood in Cambodia today, and how to prevent or reduce engagement with these
      more negative practices.

PMID- 27881049
TI  - Breaking the silence on abortion: the role of adult community abortion education
      in fostering resistance to norms.
AB  - Meanings of abortion in society are constructed within sociohistorical and
      gendered spaces and manifested through myriad discourses that impact on the
      perception and treatment of the issue in that society. In societies with powerful
      oppressive anti-abortion norms, such as Northern Ireland, little is known as to
      how these norms are resisted by the adult population. This study uses a
      Foucauldian feminist approach to show how resistance to religious and patriarchal
      norms can be fostered through adult community abortion education. This resistance
      is multi-faceted and bolstered by a lived experience discourse, which does not
      necessarily involve eschewing religious notions held within society.

PMID- 27881048
TI  - Accuracy of pre-treatment locoregional rectal cancer staging in a national
      improvement project.
AB  - BACKGROUND: The aim of this study was to assess the accuracy, particularly the
      predictive value, of locoregional clinical rectal cancer staging (cTN) and its
      variability in a national improvement project. METHODS: cTN stages and the
      distance between tumour and mesorectal fascia (MRF) were compared with
      histopathological findings in 1168 patients who underwent radical resection
      without neoadjuvant treatment. Data were registered prospectively from 2006 to
      2014. RESULTS: Agreement between clinical and histopathological TN stages was
      50%, independent of tumour location. Inter-hospital variability was within 99%
      prediction limits. Magnetic resonance imaging (MRI) was increasingly applied, but
      staging accuracy did not improve. Stage II-III was correctly predicted in 69% and
      pStage I was over-staged in 35%. The positive predictive value of endorectal
      ultrasonography (ERUS) for T1 lesions was 57%. MRI-based distances to MRF
      correlated poorly with the circumferential resection margin (r = 0.26). A
      negative resection margin was achieved in 91% when the distance to the MRF was >1
      mm. CONCLUSIONS: The accuracy of rectal cancer staging in general practice should
      be improved to avoid under- or overtreatment. Training and expert review of pre
      treatment MR imaging could be helpful. A second ERUS is justified when transanal
      local resection for early lesions is planned.

PMID- 27881050
TI  - Pharmaceutical Rejuvenation of Age-Associated Decline in Spatial Memory.
AB  - Spatial memory and cognition decline during aging. Montelukast, an FDA approved
      drug for the treatment of asthma, can restore spatial memory in old rats to
      levels similar to those of young animals. Treatment improves three hallmarks of
      aging in the brain: reducing microglial-mediated neuroinflammation, blood-brain
      barrier (BBB) permeability, and increasing neurogenesis in the hippocampus
      although not completely to youthful levels. Other aging-associated parameters,
      such as reduced synaptic density, are not affected, suggesting that anti-aging
      therapeutics may be further optimized. Montelukast targets leukotriene receptors
      GPR17 and CysLTR1 and appears to invert leukotriene signaling, converting an
      inflammatory signal into an anti-inflammatory signal. This acts as a dominant
      factor to overcome the dysfunctional effects of aging reportedly mediated, in
      part, by blood-borne factors such as beta-2 microglobulin that inhibit
      neurogenesis in the dentate gyrus of the hippocampus. The key mechanism for
      cognitive improvement by montelukast may be restoration of BBB integrity, which
      would presumably decrease the amount of deleterious blood-borne factors to enter
      the brain. Whether or not this hypothesis is true for montelukast, drugs that
      restore or maintain BBB integrity may be useful in combating age-related loss of
      cognitive function.

PMID- 27881052
TI  - Prognostic value of lactate dehydrogenase in Chinese patients with newly
      diagnosed transplant eligible multiple myeloma.

PMID- 27881054
TI  - Transition of Care for Patients with Diabetes.
AB  - BACKGROUND: Diabetes is a common chronic condition among adults that can
      complicate the transition from the hospital to the community. Hospital
      readmission is an important contributor to total medical expenditures and is an
      emerging indicator of quality of care. Failure to acknowledge diabetes transition
      of care is associated with increased emergency department visits and 30-day
      readmissions. METHODS: Literature review of transition of care models, sample
      tools and processes are presented. Updated guidelines and recommendations aiming
      to identify and address risk factors for readmission of patients with diabetes
      are provided. RESULTS: Increased attention has been given to different aspects of
      diabetes care in regards to discharge planning. This includes early initiation of
      a discharge plan identifying readmission risk factors at time of admission. In
      addition, involvement of patients, families, care givers, health care providers
      and institutions to establish transitional care. Utilization of hospital
      resources includes medication reconciliation, diabetes education, care
      coordination, discharge planning, follow up appointments and post discharge care.
      CONCLUSION: Addressing transition of care is not a choice but an important
      quality of care marker. The transition of care determines where patients with
      diabetes will follow up and how payers will remunerate hospitals for management
      of diabetes during hospitalization, discharge planning process and readmission
      rates. Different transition of care models have been identified, utilized and
      evaluated. However, more research needs to be done to establish standardized
      transitional care guidelines specific to this population.

PMID- 27881053
TI  - Oxytocin provides protection against diabetic polyneuropathy in rats.
AB  - PURPOSE: The aim of the present study is to investigate the protective effects of
      oxytocin (OT) on diabetic neuropathy (DNP) in rats. MATERIALS AND METHODS:
      Eighteen rats were used to induce diabetes using single dose streptozotocin (STZ,
      60 mg/kg). Diabetic DNP was verified by electromyography (EMG) and motor function
      test on 21st day following STZ injection. Six rats served as naive control group
      and received no drug (n = 6). Following EMG, diabetic rats were randomly divided
      into three groups and administered with either 1 ml/kg saline or 80 MUg/kg OT or
      160 MUg/kg OT intraperitoneally for four weeks. Then, EMG, motor function test,
      biochemical analysis (plasma lipid peroxides and glutathione), histological, and
      immunohistochemical analysis of sciatic nerves (bax, caspase 3, caspase 9, and
      NGF) were performed. RESULTS: Diabetic rats developed neuropathy, which was
      apparent from decreased compound muscle action potentials amplitudes and
      prolonged distal latency in saline-treated rats (p < 0.001) whereas 160 MUg/kg OT
      significantly improved EMG findings. OT treatment significantly lessened the
      thickening of perineural fibrosis when compared with saline group (p < 0.001).
      Besides, OT significantly reduced plasma lipid peroxides (p < 0.05) and increased
      glutathione levels in diabetic rats (p < 0.001). The sciatic nerves of saline
      treated rats showed considerable increase in bax, caspase 3 and caspase 8
      expressions (p < 0.001) while OT treatment significantly suppressed these
      apoptosis markers. Also, OT improved NGF expression in diabetic rats compared to
      saline group. CONCLUSION: Present results demonstrate that OT appears to
      alleviate harmful effects of hyperglycemia on peripheral neurons by suppressing
      inflammation, oxidative stress and apoptotic pathways.

PMID- 27881051
TI  - Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow
      Derived Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress
      T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways
      dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways
      dominating in humans. However, the immune suppressive pathways utilized by canine
      MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC)
      and adipose-derived MSC (Ad-MSC) been directly compared for their immune
      modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC
      were generated in vitro and their potency in suppressing T cell proliferation and
      cytokine production was compared, and differential gene expression. Mechanisms of
      T cells suppression were also investigated for both MSC types. We found that BM
      MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T
      cell activation. However, the two MSC types used both shared and distinct
      biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-beta
      signaling pathways and adenosine signaling to suppress T cell activation, whereas
      BM-MSC used cyclooxygenase, TGF-beta and adenosine signaling pathways to suppress
      T cell activation. These results indicate that canine MSC are distinct from human
      and rodent MSC terms of their immune suppressive pathways, relying primarily on
      cyclooxygenase and TGF-beta pathways for T cell suppression, rather than on NO or
      IDO-mediated pathways.

PMID- 27881055
TI  - Patents in Nanobiotechnology: A Cross Jurisdictional Approach.
AB  - BACKGROUND: Bionanomaterials create new opportunities for advancing medical
      sciences and diseases treatment in relation to human health care. Innovations in
      the use of such nanomaterials and nanodevices can lead to significant
      improvements in the use of drugs/devices. OBJECTIVE: The present study attempts
      to analyse patenting trends in different areas and compare the patentability
      criteria and the disclosure norms for nanobiotechnology inventions in countries
      such as US, EU and India in the field of diagnostics and therapeutics. METHOD:
      Nanobiotechnology patents were identified based on the search using IPC/CPC as
      well as keywords conducted on Relecura (a web-based patent and portfolio analysis
      platform). Growth of filing/ grants and by area was analysed. Comparative
      analysis of the patentability criteria was done to identify challenges in
      prosecution of nanobiotechnology applications. RESULT: US, China, followed by
      Europe are top patent filing countries in nanobiotechnology. Topic maps indicate
      medicinal preparations to be the major area of patenting. There is an increase in
      patenting in BRIC since 2000. The assessment of novelty, inventive step and
      specific disclosure norms in different jurisdictions related to nanobiotechnology
      inventions reveal challenges in patent prosecution. CONCLUSION: 79% of the
      overall nanobiotechnology patents are from the medicinal preparation area
      followed by a significant number in case of diagnostic and surgical applications.
      The upward trend in patenting indicates to the potential of inventions in the
      field of diagnostics. The development of objective and subjective criteria with
      respect to patentability indicates to elaborate patent office practice and
      prosecution in this area.

PMID- 27881056
TI  - Recent Patents on Proteasome Inhibitors of Natural Origin.
AB  - BACKGROUND: The proteasome is the major proteolytic site on the eukaryotic cell,
      degrading most of its short-lived or misfolded polypeptides. The ubiquitin
      proteasome pathway has been found to play a fundamental role in the development
      of several pathologies, from cancer to neurodegenerative diseases, or even
      retroviral infections. Nature remains a powerful source for the discovery of
      bioactive compounds. Recently, a number of molecules of natural origin, as well
      as natural product derivatives, have been described as proteasome inhibitors.
      Most of these molecules directly block one or more catalytic sites of the 20S
      proteasome, but some of them act upstream of proteolytic degradation, for
      instance, inhibiting the ubiquitin tagging process. OBJECTIVES: The present
      review focuses on recent patents on proteasome inhibitors of natural origin,
      their derivatives and synthetic routes to obtain such molecules, as well as their
      application as a tool in chemotherapy. CONCLUSION: With several of these
      modulators of the ubiquitin-proteasome system under clinical trials, we hope that
      the next few years lead to the development of new pharmaceutical drugs and
      characterization of new proteasome inhibitors of natural origin or inspiration.

PMID- 27881057
TI  - Recent Patents on Heat Shock Proteins Targeting Antibodies.
AB  - BACKGROUND: Heat shock proteins (Hsp) are major chaperone molecules that have
      recently emerged as cancer therapeutic targets owing to their involvement in
      tumor cell proliferation, differentiation, invasion and metastasis. High levels
      of extracellular Hsp90 and Hsp70 have been closely associated with a wide range
      of human cancers. Accumulating evidence suggests that the pharmacological
      inhibition of these molecules can play a pivotal role in non-surgical cancer
      treatment. Efforts have been taken to develop monoclonal antibodies (mAbs) and
      antibody fragments targeting extracellular Hsp90 and Hsp70, alone or conjugated
      with standard anticancer agents, to control several types of cancer, such as
      breast, colon, prostate or melanoma. OBJECTIVE: To provide an overview on the
      development of monoclonal antibodies and antibody fragments with capacity to bind
      Hsp90 and Hsp70, aiming at being used for cancer treatment. METHODS: A systematic
      review was performed using European Patent Office and Google patents databases.
      RESULTS: Based on the available literature and patents, we report the potential
      anticancer strategies based on these biological molecules. CONCLUSIONS: Supported
      by the recent developments in this field, Hsp targeting antibodies therapy may
      emerge for clinical use in the future for cancer patients, namely as antibody
      drug conjugates combining the specificity of these antibodies with the potency of
      cytotoxic drugs.

PMID- 27881058
TI  - The Relationship Between Systemic Lupus Erythematosus Activity and Persistent
      Positive Antiphospholipid Antibodies.
AB  - BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder,
      characterized by producing different auto-antibodies and multiorgan involvements.
      In this study we aimed to investigate the relationship between SLE activity and
      persistently positive antiphospholipid antibodies. OBJECTIVE/METHODS: Fifty-nine
      lupus patients (55 women and 4 men) who were assessed in two consecutive visits
      with 6 weeks interval were selected. Patients' clinical and laboratory data and
      serum antiphospholipid antibodies' values, were collected. Serum anticardiolipin
      antibodies and lupus anticoagulant were measured in two visits. The correlations
      between these antibodies with SLEDAI and with major organ involvements were
      assessed. We found that SLEDAI was significantly higher in persistently positive
      aPLs patients compared with persistently negative aPLs patients. A positive
      correlation between IgG-aCL antibody titer and SLEDAI at first visit (P=0.049)
      was also seen. RESULT AND CONCLUSION: The results showed that disease activity in
      SLE was associated with increased APAs and persistent positive antiphospholipid
      antibodies may indicate higher lupus disease activity.

PMID- 27881059
TI  - Natural Products with Antiplatelet Action.
AB  - BACKGROUND: Complex hemostatic mechanisms are involved in the pathophysiology of
      various diseases, including cardiovascular diseases. Among them, dysregulation of
      platelet activity is linked to the progression of atherosclerosis and mainly
      involves platelet aggregation and a decrease in blood flow in the vascular
      endothelium. The major platelet activation pathways mediated by agonists involve
      the arachidonic acid pathway, adenosine diphosphate pathway, serotonin pathway,
      nitric oxide pathway, and action of free radicals on molecules involved in
      platelet aggregation. These mechanisms have been widely studied and discussed
      because they are inhibited by the use of medicinal plants in complementary and
      alternative medicine, thus reducing platelet aggregation. RESULTS: Of the main
      plants discussed in this review, which have antiplatelet activity, some include
      saffron, garlic, green tea, St. John's wort, ginger, ginkgo biloba, ginseng, and
      guavirova. These herbal medicines have phytochemical components, which are
      directly related to the antiplatelet activity of the plant, such as flavonoids,
      curcumins, catechins, terpenoids, polyphenols, and saponins. While the majority
      of the medicinal plants mentioned here were native to the Asian continents, some
      are distributed worldwide, and found to a smaller extent throughout the American
      continent, European continent, Mediterranean, African continent, and the Middle
      East. CONCLUSION: This review showed that several plants and/or compounds exhibit
      anti-platelet activity, and are therefore potential research targets for
      developing drugs to treat diseases related to aggregation disorders.

PMID- 27881060
TI  - Hormones and Sarcopenia.
AB  - Sarcopenia is defined as the loss of muscle mass associated with a loss of muscle
      function, e.g., walking speed. A number of consensus definitions exist for
      sarcopenia with cut-off points being ethnically specific. A rapid screen test
      (SARC-F) is available and does not require different ethnic cut-off points.
      Sarcopenia leads to the development of frailty, disability and mortality. The
      prevalence of sarcopenia varies from 1-29% in community- dwelling and 14 to 33%
      in long-term care populations. Hormones play a role in the development of muscle
      mass and in the regulation of muscle strength. Testosterone appears to be the
      central hormone involved in the development of sarcopenia; it increases both
      muscle mass and activates satellite cells leading to increased muscle function.
      Growth hormone deficiency leads to the loss of muscle mass but not muscle
      strength. Lack of insulin or insulin resistance leads to accelerated development
      of sarcopenia. Vitamin D deficiency plays a role in the loss of muscle strength.
      A variety of other hormones appear to play minor roles in age-related alterations
      in muscle mass and function. At present, the treatment of sarcopenia is
      resistance exercise, leucine enriched essential amino acids or
      hydroxymethylbutyrate and vitamin D replacement.

PMID- 27881061
TI  - Traditional and Alternative Therapies for Refractory Angina.
AB  - Refractory angina (RFA) is an unfavourable condition that is characterized with
      persistent angina due to reversible myocardial ischemia in patients with coronary
      artery disease that remains uncontrollable despite an optimal combination of
      pharmacological agents and revascularization. Despite significant advances in
      revascularization techniques and agents used in pharmacological therapy, there is
      still a significant population suffering from RFA and the global prevalence is
      even increasing. Anti- anginal treatment and secondary risk-factor modification
      are the traditional approaches for this group of patients. Furthermore, now there
      is still a large number of alternative treatment options. In order to review
      traditional and alternative treatment strategies in patients with RFA, we
      searched Pubmed for articles in English using the search terms "pharmacological
      therapy, refractory angina", "alternative therapy, refractory angina" between
      inception to June 2016. We also went through separately for each alternative
      treatment modality on Pubmed. To identify further articles, we handsearched
      related citations in review articles and commentaries. We also included data from
      the European Society of Cardiology (2013), and the Canadian Society of
      Cardiology/ Canadian Pain Society (2012) guidelines. Data show that besides
      traditional pharmacological agents, such as nitrates, beta- blockers or calcium
      channel blockers, novel antiischemic drugs and if symptoms persist, several non-
      invasive and/ or invasive alternative strategies may be considered. Impact of
      some pharmacological agents, such as rho- kinase inhibitors, and novel
      alternative treatment modalities, such as coronary sinus reducers, stem cell
      therapy, gene and protein therapy, on outcomes are still under investigation.

PMID- 27881062
TI  - Antihypertensive Treatments in Patients Affected by Aortic Valve Stenosis.
AB  - Systemic hypertension and aortic valve stenosis (AVS) are both age-related
      diseases. Severe aortic stenosis affects ~2% to 5% of adults age > 65 years.
      Systemic hypertension is a frequent comorbidity in patients with AVS and is
      coexistent for a longer period of time before AVS is treated. Essential systemic
      hypertension, per se, plays an important role in the creation of lesions on the
      aortic side of the valve, the region of higher exposure to tension stress. The
      subsequent endothelial defect represents the principal site of inflammatory
      process and oxidative stress, leading to aortic sclerosis and calcification. In
      this review, we want to describe the pharmacological features of the common
      antihypertensive drugs, analysing the recent literature, in order to achieve
      useful and updated information about the best treatment of systemic hypertension
      in patients with concomitant severe aortic stenosis.

PMID- 27881063
TI  - Membrane Bioreactors for Pharmaceutical Applications: Optically Pure Enantiomers
      Production.
AB  - In biological systems, recognition at molecular level is governed by chiral
      interactions. Therefore, optical isomers have very different effect in natural
      systems. For example, one can have beneficial effect while the other can be very
      harmful. For these reasons, chiral drugs nowadays are mainly admitted in the
      optically pure form. Given these requirements, it is clear why demand for chiral
      drugs has grown dramatically and the singleenantiomer drug segment has become an
      important part of the overall pharmaceutical market. As a consequence, the
      development of new chiral separation techniques is a very hot topic in both
      academic research and industrial innovation. Membrane bioreactors have proven
      their feasibility in the production of optically pure enantiomers by combining
      enantiospecific biochemical reactions with mass transport through membranes. The
      principles and the applications of enantioselective membrane bioreactors in
      kinetic resolution for pharmaceutical applications will be discussed. Various
      membrane bioreactors configurations and operation mode will be illustrated. The
      type of enzymes utilized to produce chiral drugs or their intermediates will be
      also reported. Multistep syntheses, conducted in sequential reactions catalysed
      by spatially aligned biocatalysts, as promising technology for the synthesis of
      fine chemicals will be highlighted.

PMID- 27881065
TI  - Lipids at the Cross-road of Autoimmunity in Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central
      nervous system (CNS) characterized by demyelination and neurodegeneration, driven
      by a Th17/Th1-immune response, which afflicts mainly young women. Although MS
      causes are not completely known, it is notorious that the disease is
      characterized by an extended focal degradation of the myelin sheath, with
      ulterior axonal and neuronal damage. Lipid molecules play a main dual role in MS,
      both as target molecules of myelin destruction and as mediators of inflammation.
      Indeed, recent cumulative evidence suggests that abnormalities in the
      lipidbinding proteins of myelin and sphingolipid content that confer increased
      immunogenicity may underlie the autoimmune response against the myelin sheath.
      CNS is after all, the second organ richer in lipid content after adipose tissue.
      On the other hand, soluble factors called adipokines, secreted by adipose tissue,
      modulate inflammatory responses and contribute to metabolic dysfunction, which
      may be important in MS pathophysiology. Disability accumulation in MS patients is
      slow but persistent, often leading to a decreased mobility and physical activity,
      resulting in more weakness, fatigue and associated increased risk of the
      metabolic syndrome (MetS). In turn, MetS may trigger MS in susceptible
      individuals and is a bad prognostic factor. Here we review what are the facts
      linking lipids, MetS and MS, what we do not know yet, and what we should do to
      move this field forward.

PMID- 27881066
TI  - New Insights Emerging from Recent Investigations on Human Group II Pyridoxal 5'
      Phosphate Decarboxylases.
AB  - Aromatic amino acid, cysteine sulfinic acid, glutamate and histidine
      decarboxylases, belonging to group II of pyridoxal 5'-phosphate-dependent
      enzymes, catalyze the synthesis of dopamine/serotonin, hypotaurine, gamma
      aminobutyric acid and histamine, respectively. Considering that these reaction
      products are all essential bioactive molecules, group II decarboxylases have been
      long studied from an evolutionary, biochemical and pharmacological standpoint.
      Despite the fact that they all belong to a common fold-type, during evolution
      each decarboxylase has evolved unique structural elements responsible for its
      substrate specificity. Combining a literature update with bioinformatic analyses,
      this review focuses on some structural determinants shared by these enzymes
      revealing their intrinsic substrate specificity and highlighting the importance
      of some residues/regions for catalytic competence. In particular, two key
      structural features emerge: 1) a mobile catalytic loop, and 2) an open-to-close
      conformation accompanying the apo-holo transition. Drawing attention on these
      elements is crucial in correlating subtle structural modifications to functional
      properties for the understanding, at a molecular level of a pathological
      condition. This is corroborated by the increasingly important role played by
      these decarboxylases in several different pathological states (autoimmune
      diseases, type I diabetes, Parkinson's disease, aromatic amino acid decarboxylase
      deficiency, Tourette's syndrome and cholangiocarcinoma).

PMID- 27881064
TI  - Functional Foods for Health: The Interrelated Antioxidant and Anti-Inflammatory
      Role of Fruits, Vegetables, Herbs, Spices and Cocoa in Humans.
AB  - The health benefits of plant food-based diets could be related to both integrated
      antioxidant and antiinflammatory mechanisms exerted by a wide array of
      phytochemicals present in fruit, vegetables, herbs and spices. Therefore, there
      is mounting interest in identifying foods, food extracts and phytochemical
      formulations from plant sources which are able to efficiently modulate oxidative
      and inflammatory stress to prevent diet-related diseases. This paper reviews
      available evidence about the effect of supplementation with selected fruits,
      vegetables, herbs, spices and their extracts or galenic formulation on combined
      markers of redox and inflammatory status in humans.

PMID- 27881067
TI  - Emerging Nanocarriers-based Approaches to Diagnose and Red uce Vascular
      Inflammation in Atherosclerosis.
AB  - Exploitation of nanotechnology advances in the cardiovascular medicine has led to
      new approaches for the diagnosis and therapy of vascular inflammation associated
      to cardiovascular diseases. Innovative nanoparticles targeted to the main players
      in the arterial wall inflammation in atherosclerosis (i.e. inflammatory
      molecules, immune or resident cells) have been already developed to diagnose
      and/or reduce excessive vascular inflammation and is eagerly awaited that
      promising preclinical and early clinical results to boost the approval of the
      first nanocarrier in this field. This review discusses the challenges and the
      steps undertaken so far to produce powerful multifunctional nanoparticles capable
      of raising new scenarios for future precision medicine in atherosclerosis.

PMID- 27881068
TI  - Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory
      Hypothesis in Amyotrophic Lateral Sclerosis Revisited.
AB  - Research onto the pathogenesis of amyotrophic lateral sclerosis (ALS) has
      obtained notable gene discoveries, although, to date, only progress with regard
      to treatment has been very modest. Currently ALS is considered a multifactorial
      disease that presents diverse clinical presentations, ranging from a monogenic
      inherited disease to an autoimmune pathology, and develops with misfolded protein
      aggregation and neuroinflammation. An important factor related to ALS
      pathogenesis is the microglial activation associated with degenerative motor
      neurons. This activation leads to changes in the expression of a wide range of
      genes related to phagocytosis and inflammation, and to profound modifications in
      the dynamic interactions between neurons and glial cells. Overactivation and
      deregulation of microglial activity causes deleterious effects and leads to
      neuronal death. However, the involvement of microglia in non-inflammatory
      functions challenges our concept of neuroinflammation and opens up new
      possibilities for the study of the pathophysiological mechanisms of ALS. In this
      review we summarize the current knowledge on the adaptive interactions between
      neurons and microglia in ALS. We also discuss the hypothesis that controlling the
      extent of microglial activation and neuroinflammation may have clinical and
      therapeutic benefits for the condition.

PMID- 27881069
TI  - Anti-influenza Virus Effects of Catechins: A Molecular and Clinical Review.
AB  - Influenza infection and associated epidemics represent a serious public health
      problem. Several preventive and curative measures exist against its spread
      including vaccination and therapeutic agents such as neuraminidase inhibitors
      (e.g., oseltamivir, zanamivir, as well as peramivir and laninamivir, which are
      licensed in several countries) and adamantanes (e.g., amantadine and
      rimantadine). However, neuraminidase inhibitor- and adamantane- resistant viruses
      have been detected, whereas vaccines exhibit strain-specific effects and are
      limited in supply. Thus, new approaches are needed to prevent and treat influenza
      infections. Catechins, a class of polyphenolic flavonoids present in tea leaves,
      have been reported as potential anti-influenza virus agents based on experimental
      and clinical studies. (-)-epigallocatechin gallate (EGCG), a major and highly
      bioactive catechin, is known to inhibit influenza A and B virus infections in
      Madin-Darby canine kidney cells. Additionally, EGCG and other catechin compounds
      such as epicatechin gallate and catechin-5-gallate also show neuraminidase
      inhibitory activities as demonstrated via molecular docking. These catechins can
      bind differently to neuraminidase and might overcome known drug resistancerelated
      virus mutations. Furthermore, the antiviral effects of chemically modified
      catechin derivatives have also been investigated, and future structure-based drug
      design studies of catechin derivatives might contribute to improvements in
      influenza prevention and treatment. This review briefly summarizes probable
      mechanisms underlying the inhibitory effects of tea catechins against influenza
      infection and their clinical benefits on influenza prevention and treatment.
      Additionally, the great potential of tea catechins and their chemical derivatives
      as effective antiviral agents is described.

PMID- 27881070
TI  - Pregnancy-Specific beta1-Glycoproteins: Combined Biomarker Roles,
      Structure/Function Relationships and Implications for Drug Design.
AB  - BACKGROUND: Pregnancy specific beta1-glycoproteins (PSGs) have long been
      recognized as trophoblast quality and embryo viability markers. However,
      biological roles of PSGs remain obscure, and structure/function relationships to
      other feto-placental proteins as well as implications for drug design have not
      been reviewed. This review summarizes and discusses advances in 45-year studies
      of PSGs with focus on the latest achievements and the challenges for future
      investigations. METHODS: Literature search was performed to review the majority
      of recent PSG studies with emphasis on usage of high-throughput integrated
      proteomic profiling technologies, systems biology and bioinformatics approaches
      that enhance novel biomarker and drug target discovery as well as protein
      structure/activity analysis. RESULTS: Clinical significance and screening
      performance improved when PSG measurements were combined with those of other
      placenta-derived proteins: hCG, hPL, PAPP-A, and proMBP. Nevertheless, analysis
      of protein co-expression and co-localization data and the involvement of PSGs in
      protein interaction networks are being introduced to discover novel, specific and
      high-sensitive, gestational/cancer biomarkers. Despite biological roles of PSGs
      are not fully understood, there are evidences of that they exhibit
      immunomodulatory, antiinflammatory and proangiogenic effects. Investigation of
      structure/function relationships showed that PSGs may function in
      cooperative/coordinated manner with numerous regulatory proteins including alpha
      fetoprotein and transforming growth factors-beta; this is provided by the
      presence of conserved short linear motifs (SLiMs) such as RGD, PXXP and AFP14-20
      like (YXCX) ones. CONCLUSION: PSG-derived peptides may be used as a rationale to
      design novel drugs that mimic SLiMs involved in protein-protein interactions to
      inhibit domain-motif binding and to block cell signaling, and/or exert
      immunomodulatory, anti-inflammatory and proangiogenic effects.

PMID- 27881072
TI  - Patients with longstanding ulcerative colitis in remission do not have more
      irritable bowel syndrome-like symptoms than controls.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is more common in patients with
      ulcerative colitis (UC) than expected. The prevalence of IBS in patients with UC
      with longstanding disease is not known. We investigated the prevalence of IBS
      like symptoms in patients with UC in remission and longstanding disease in
      comparison to control subjects. METHODS: Sixty-eight patients with UC and 33
      patients with hereditary familiar colon cancer and who underwent colonoscopy
      surveillance were included. Faecal calprotectin (FC), Gastrointestinal Symptoms
      Rating Scale-Irritable Bowel Syndrome (GSRS-IBS) and Hospital Anxiety and
      Depression scale were fulfilled prior to endoscopy. UC in remission was define by
      steroid-free clinical remission, a Mayo Score <= 1 on endoscopy, a FC <= 200
      MUg/g and no significant active inflammation on colon biopsies. RESULTS: Fifty
      five UC patients met the criteria for being in remission. The median disease
      duration was 17 years. The patients with UC in remission tended to have lower
      scores on total GSRS-IBS score (6 vs 10.5; p = 0.062) and lower or equal scores
      on all specific IBS symptoms in comparison to controls. There was a moderate but
      significant correlation between diarrhoea scores and FC levels (in the span <=
      200 MUg/g) (rs 0.38; p = 0.004) in the UC in remission group. CONCLUSION:
      Patients with UC with longstanding disease and in remission do not have more IBS
      symptoms than controls. In UC patients in remission the FC level in the lower
      span showed a moderate correlation to symptoms of diarrhoea.

PMID- 27881073
TI  - Bilingualism in older Mexican-American immigrants is associated with higher
      scores on cognitive screening.
AB  - BACKGROUND: Bilingualism may protect against cognitive aging and delay the onset
      of dementia. However, studies comparing monolinguals and bilinguals on such
      metrics have produced inconsistent results complicated by confounding variables
      and methodological concerns. METHODS: We addressed this issue by comparing
      cognitive performance in a more culturally homogeneous cohort of older Spanish
      speaking monolingual (n = 289) and Spanish-English bilingual (n = 339) Mexican
      American immigrants from the Sacramento Longitudinal Study on Aging. RESULTS:
      After adjusting for demographic differences and depressive symptoms, both groups
      performed similarly at baseline on verbal memory but the bilingual group
      performed significantly better than the monolingual group on a cognitive
      screening test, the Modified Mini-Mental State Examination (3MS; p < 0.001).
      Group differences on the 3MS were driven by language/executive and
      language/praxis factors. Within the bilingual group, neither language of testing
      nor degree of bilingualism was significantly associated with 3MS or verbal memory
      scores. Amongst individuals who performed in the normal or better range on both
      tests at baseline and were followed for an average of 6 years, both monolinguals
      and bilinguals exhibited similar rates of cognitive decline on both measures.
      CONCLUSIONS: These findings suggest that bilingualism is associated with modest
      benefits in cognitive screening performance in older individuals in cross
      sectional analyses that persist across longitudinal analyses. The effects of
      bilingualism should be considered when cognitively screening is performed in
      aging immigrant populations.

PMID- 27881074
TI  - Changes of gonadotropin-releasing hormone receptor 2 during the anadromous
      spawning migration in Coilia nasus.
AB  - BACKGROUND: An increase in the activity of the pituitary-gonad axis (PG-axis) and
      gonad development are essential for the onset of spawning migration in teleosts.
      In the fish Coilia nasus, gonad development and spawning migration up the Yangtze
      River occurs by the end of each summer. We hypothesized that gonadotropin
      releasing hormones receptor 2 (GnRH-R2), which together produce a signal that
      interacts with the PG-axis, may help to regulate spawning migration processes.
      RESULTS: In this regard, we (1) characterized the gonadosomatic index (GSI) in
      the anadromous fish C. nasus; (2) analyzed the GnRH-R2 mRNA expression levels in
      ovary and brain, and concentrations in the serum; and (3) identified the GnRH-R2
      protein distribution in the brain and ovaries. We found strong relationships
      between all of these indices. CONCLUSIONS: The results indicate that GnRH-R2
      could act together to promote spawning during the anadromous migration. There is
      some evidence that the GnRH-R2 gene expression levels and protein distributions
      change in association with the migratory behavior.

PMID- 27881071
TI  - Genome-wide analyses of chitin synthases identify horizontal gene transfers
      towards bacteria and allow a robust and unifying classification into fungi.
AB  - BACKGROUND: Chitin, the second most abundant biopolymer on earth after cellulose,
      is found in probably all fungi, many animals (mainly invertebrates), several
      protists and a few algae, playing an essential role in the development of many of
      them. This polysaccharide is produced by type 2 glycosyltransferases, called
      chitin synthases (CHS). There are several contradictory classifications of CHS
      isoenzymes and, as regards their evolutionary history, their origin and diversity
      is still a matter of debate. RESULTS: A genome-wide analysis resulted in the
      detection of more than eight hundred putative chitin synthases in proteomes
      associated with about 130 genomes. Phylogenetic analyses were performed with
      special care to avoid any pitfalls associated with the peculiarities of these
      sequences (e.g. highly variable regions, truncated or recombined sequences, long
      branch attraction). This allowed us to revise and unify the fungal CHS
      classification and to study the evolutionary history of the CHS multigenic
      family. This update has the advantage of being user-friendly due to the
      development of a dedicated website ( http://wwwabi.snv.jussieu.fr/public/CHSdb ),
      and it includes any correspondences with previously published classifications and
      mutants. Concerning the evolutionary history of CHS, this family has mainly
      evolved via duplications and losses. However, it is likely that several
      horizontal gene transfers (HGT) also occurred in eukaryotic microorganisms and,
      even more surprisingly, in bacteria. CONCLUSIONS: This comprehensive multi
      species analysis contributes to the classification of fungal CHS, in particular
      by optimizing its robustness, consensuality and accessibility. It also highlights
      the importance of HGT in the evolutionary history of CHS and describes bacterial
      chs genes for the first time. Many of the bacteria that have acquired a chitin
      synthase are plant pathogens (e.g. Dickeya spp; Pectobacterium spp; Brenneria
      spp; Agrobacterium vitis and Pseudomonas cichorii). Whether they are able to
      produce a chitin exopolysaccharide or secrete chitooligosaccharides requires
      further investigation.

PMID- 27881075
TI  - Modelling microbial metabolic rewiring during growth in a complex medium.
AB  - BACKGROUND: In their natural environment, bacteria face a wide range of
      environmental conditions that change over time and that impose continuous
      rearrangements at all the cellular levels (e.g. gene expression, metabolism).
      When facing a nutritionally rich environment, for example, microbes first use the
      preferred compound(s) and only later start metabolizing the other one(s). A
      systemic re-organization of the overall microbial metabolic network in response
      to a variation in the composition/concentration of the surrounding nutrients has
      been suggested, although the range and the entity of such modifications in
      organisms other than a few model microbes has been scarcely described up to now.
      RESULTS: We used multi-step constraint-based metabolic modelling to simulate the
      growth in a complex medium over several time steps of the Antarctic model
      organism Pseudoalteromonas haloplanktis TAC125. As each of these phases is
      characterized by a specific set of amino acids to be used as carbon and energy
      source our modelling framework describes the major consequences of nutrients
      switching at the system level. The model predicts that a deep metabolic
      reprogramming might be required to achieve optimal biomass production in
      different stages of growth (different medium composition), with at least half of
      the cellular metabolic network involved (more than 50% of the metabolic genes).
      Additionally, we show that our modelling framework is able to capture metabolic
      functional association and/or common regulatory features of the genes embedded in
      our reconstruction (e.g. the presence of common regulatory motifs). Finally, to
      explore the possibility of a sub-optimal biomass objective function (i.e. that
      cells use resources in alternative metabolic processes at the expense of optimal
      growth) we have implemented a MOMA-based approach (called nutritional-MOMA) and
      compared the outcomes with those obtained with Flux Balance Analysis (FBA).
      Growth simulations under this scenario revealed the deep impact of choosing among
      alternative objective functions on the resulting predictions of fluxes
      distribution. CONCLUSIONS: Here we provide a time-resolved, systems-level scheme
      of PhTAC125 metabolic re-wiring as a consequence of carbon source switching in a
      nutritionally complex medium. Our analyses suggest the presence of a potential
      efficient metabolic reprogramming machinery to continuously and promptly adapt to
      this nutritionally changing environment, consistent with adaptation to fast
      growth in a fairly, but probably inconstant and highly competitive, environment.
      Also, we show i) how functional partnership and co-regulation features can be
      predicted by integrating multi-step constraint-based metabolic modelling with fed
      batch growth data and ii) that performing simulations under a sub-optimal
      objective function may lead to different flux distributions in respect to
      canonical FBA.

PMID- 27881076
TI  - Clustering of disulfide-rich peptides provides scaffolds for hit discovery by
      phage display: application to interleukin-23.
AB  - BACKGROUND: Disulfide-rich peptides (DRPs) are found throughout nature. They are
      suitable scaffolds for drug development due to their small cores, whose disulfide
      bonds impart extraordinary chemical and biological stability. A challenge in
      developing a DRP therapeutic is to engineer binding to a specific target. This
      challenge can be overcome by (i) sampling the large sequence space of a given
      scaffold through a phage display library and by (ii) panning multiple libraries
      encoding structurally distinct scaffolds. Here, we implement a protocol for
      defining these diverse scaffolds, based on clustering structurally defined DRPs
      according to their conformational similarity. RESULTS: We developed and applied a
      hierarchical clustering protocol based on DRP structural similarity, followed by
      two post-processing steps, to classify 806 unique DRP structures into 81
      clusters. The 20 most populated clusters comprised 85% of all DRPs.
      Representative scaffolds were selected from each of these clusters; the
      representatives were structurally distinct from one another, but similar to other
      DRPs in their respective clusters. To demonstrate the utility of the clusters,
      phage libraries were constructed for three of the representative scaffolds and
      panned against interleukin-23. One library produced a peptide that bound to this
      target with an IC50 of 3.3 MUM. CONCLUSIONS: Most DRP clusters contained members
      that were diverse in sequence, host organism, and interacting proteins,
      indicating that cluster members were functionally diverse despite having similar
      structure. Only 20 peptide scaffolds accounted for most of the natural DRP
      structural diversity, providing suitable starting points for seeding phage
      display experiments. Through selection of the scaffold surface to vary in phage
      display, libraries can be designed that present sequence diversity in
      architecturally distinct, biologically relevant combinations of secondary
      structures. We supported this hypothesis with a proof-of-concept experiment in
      which three phage libraries were constructed and panned against the IL-23 target,
      resulting in a single-digit MUM hit and suggesting that a collection of libraries
      based on the full set of 20 scaffolds increases the potential to identify
      efficiently peptide binders to a protein target in a drug discovery program.

PMID- 27881078
TI  - No rationale for 1 variable per 10 events criterion for binary logistic
      regression analysis.
AB  - BACKGROUND: Ten events per variable (EPV) is a widely advocated minimal criterion
      for sample size considerations in logistic regression analysis. Of three previous
      simulation studies that examined this minimal EPV criterion only one supports the
      use of a minimum of 10 EPV. In this paper, we examine the reasons for substantial
      differences between these extensive simulation studies. METHODS: The current
      study uses Monte Carlo simulations to evaluate small sample bias, coverage of
      confidence intervals and mean square error of logit coefficients. Logistic
      regression models fitted by maximum likelihood and a modified estimation
      procedure, known as Firth's correction, are compared. RESULTS: The results show
      that besides EPV, the problems associated with low EPV depend on other factors
      such as the total sample size. It is also demonstrated that simulation results
      can be dominated by even a few simulated data sets for which the prediction of
      the outcome by the covariates is perfect ('separation'). We reveal that different
      approaches for identifying and handling separation leads to substantially
      different simulation results. We further show that Firth's correction can be used
      to improve the accuracy of regression coefficients and alleviate the problems
      associated with separation. CONCLUSIONS: The current evidence supporting EPV
      rules for binary logistic regression is weak. Given our findings, there is an
      urgent need for new research to provide guidance for supporting sample size
      considerations for binary logistic regression analysis.

PMID- 27881077
TI  - Sex difference in EGFR pathways in mouse kidney-potential impact on the immune
      system.
AB  - BACKGROUND: Epidermal growth factor receptor (Egfr) has been the target of
      several drugs for cancers. The potential gender differences in genes in the Egfr
      axis have been suggested in humans and in animal models. Female and male mice
      from the same recombinant inbred (RI) strain have the same genomic components
      except the sex difference. A population of different RI mouse strains allows to
      conduct precise analysis of molecular pathways and regulation of Egfr between
      female and male mice. METHODS: The whole genome expression profiles of 70
      genetically diverse RI strains of mice were used to compare three major molecular
      aspects of Egfr gene: the relative expression levels, gene network and expression
      quantitative trait loci (eQTL) that regulate the expression of Egfr between
      female and male mice. RESULTS: Our data showed that there is a significant sex
      difference in the expression levels in kidney. A considerable number of genes in
      the gene network of Egfr are sex differentially expressed. The expression levels
      of Egfr in mice are statistical significant different between C57BL/6 J (B6) and
      DBA/2 J (D2) genotypes in male while no difference in female mice. The eQTLs that
      regulate the expression levels of Egfr between female and male mice are also
      different. Furthermore, the differential expression levels of Egfr showed
      significantly different correlations with two known biological traits between
      male and female mice. CONCLUSION: Overall there is a substantial sex difference
      in the Egfr pathways in mice. These data may have significant impact on drug
      target design, development, formulation, and dosage determinant for women and men
      in clinical trials.

PMID- 27881079
TI  - Detection of West Nile virus in wild birds in Tana River and Garissa Counties,
      Kenya.
AB  - BACKGROUND: West Nile fever virus is a zoonotic arboviral infection maintained in
      a sylvatic cycle involving mosquito vectors and birds. It is one the arboviruses
      whose geographical range is expanding because of climate and land use changes
      that enhance the densities of mosquitoes and promote mosquito-bird-human
      interactions. We carried out a survey to determine the reservoirs of WNV among
      wild birds in Tana River and Garissa counties, Kenya. METHODS: Blood samples were
      obtained from 361 randomly trapped wild birds. Using real-time polymerase chain
      reaction (PCR), all samples were screened for WNV using gene specific primer sets
      amplifying a portion of the E region of the genome encoding the envelope protein.
      RESULTS: Sixty five (65) out of 361 birds screened tested positive for WNV on
      real-time PCR assay. Sequencing of the selected positive samples reveals that the
      isolated WNV were most closely related to strains isolated from China (2011). A
      regression analysis indicated that sampling location influenced the occurrence of
      WNV while species, age, weight and sex of the birds did not have any effect.
      CONCLUSIONS: This study provides baseline information on the existing circulation
      of WNV in this region among wild bird reservoirs that could spill over to the
      human population and points to the need for implementation of surveillance
      programs to map the distribution of the virus among reservoirs. Awareness
      creation about West Nile fever in this region is important to improve its
      detection and management.

PMID- 27881082
TI  - Quality assurance of human papillomavirus (HPV) testing in the implementation of
      HPV primary screening in Norway: an inter-laboratory reproducibility study.
AB  - BACKGROUND: Human papillomavirus (HPV) testing as primary screening for cervical
      cancer is currently being implemented in Norway in a randomized controlled
      fashion, involving three laboratories. As part of the quality assurance programme
      of the implementation, an evaluation of the inter-laboratory reproducibility of
      the HPV test was initiated, to ensure satisfactory HPV test reliability in all
      three laboratories. METHODS: The HPV test used is the cobas 4800 HPV Test,
      detecting 14 high-risk types with individual HPV genotype results for HPV16 and
      HPV18. In addition to the three laboratories involved in the implementation, the
      Norwegian HPV reference laboratory was included as a fourth comparative
      laboratory. A stratified sample of 500 cervical liquid based cytology (LBC)
      samples was used in the evaluation, with an aim towards a high-risk HPV
      positivity of ~25%. Samples were collected at one laboratory, anonymized,
      aliquoted, and distributed to the other laboratories. RESULTS: Comparison of the
      test results of all four laboratories revealed a 95.6% agreement, an 86.3%
      positive agreement and a kappa value of 0.94 (95% CI 0.92-0.97). For negative
      cytology specimens, there was a 95.8% overall agreement, a 67.4% positive
      agreement, and a kappa value of 0.88 (95% CI 0.80-0.93). For abnormal cytology
      specimens, there was a 95.8% overall agreement, a 95.5% positive agreement, and a
      kappa value of 0.86 (95% CI 0.71-0.97). CONCLUSIONS: The study showed a high
      inter-laboratory reproducibility of HPV testing, implying satisfactory user
      performance and reliability in the laboratories involved in the implementation
      project. This is important knowledge and we recommend similar studies always to
      be performed prior to the introduction of new screening routines.

PMID- 27881080
TI  - Genotypic differences in intruder-evoked immediate early gene activation in male,
      but not female, vasopressin 1b receptor knockout mice.
AB  - BACKGROUND: The neuropeptide arginine vasopressin (Avp) modulates social
      behaviors via its two centrally expressed receptors, the Avp 1a receptor and the
      Avp 1b receptor (Avpr1b). Recent work suggests that, at least in mice, Avp
      signaling through Avpr1b within the CA2 region of the hippocampus is critical for
      normal aggressive behaviors and social recognition memory. However, this brain
      area is just one part of a larger neural circuit that is likely to be impacted in
      Avpr1b knockout (-/-) mice. To identify other brain areas that are affected by
      altered Avpr1b signaling, genotypic differences in immediate early gene
      activation, i.e. c-FOS and early growth response factor 1 (EGR-1), were
      quantified using immunocytochemistry following a single exposure to an intruder.
      RESULTS: In females, no genotypic differences in intruder-evoked c-FOS or EGR-1
      immunoreactivity were observed in any of the brain areas measured. In males,
      while there were no intruder-evoked genotypic differences in c-FOS
      immunoreactivity, genotypic differences were observed in EGR-1 immunoreactivity
      within the ventral bed nucleus of the stria terminalis and the anterior
      hypothalamus; with Avpr1b -/- males having less EGR-1 immunoreactivity in these
      regions than controls. CONCLUSIONS: These data are the first to identify specific
      brain areas that may be a part of a neural circuit that includes Avpr1b
      expressing cells in the CA2 region of the hippocampus. It is thought that this
      circuit, when working properly, plays a role in how an animal evaluates its
      social context.

PMID- 27881081
TI  - Phylogenetic distribution of plant snoRNA families.
AB  - BACKGROUND: Small nucleolar RNAs (snoRNAs) are one of the most ancient families
      amongst non-protein-coding RNAs. They are ubiquitous in Archaea and Eukarya but
      absent in bacteria. Their main function is to target chemical modifications of
      ribosomal RNAs. They fall into two classes, box C/D snoRNAs and box H/ACA
      snoRNAs, which are clearly distinguished by conserved sequence motifs and the
      type of chemical modification that they govern. Similarly to microRNAs, snoRNAs
      appear in distinct families of homologs that affect homologous targets. In
      animals, snoRNAs and their evolution have been studied in much detail. In plants,
      however, their evolution has attracted comparably little attention. RESULTS: In
      order to chart the phylogenetic distribution of individual snoRNA families in
      plants, we applied a sophisticated approach for identifying homologs of known
      plant snoRNAs across the plant kingdom. In response to the relatively fast
      evolution of snoRNAs, information on conserved sequence boxes, target sequences,
      and secondary structure is combined to identify additional snoRNAs. We identified
      296 families of snoRNAs in 24 species and traced their evolution throughout the
      plant kingdom. Many of the plant snoRNA families comprise paralogs. We also found
      that targets are well-conserved for most snoRNA families. CONCLUSIONS: The
      sequence conservation of snoRNAs is sufficient to establish homologies between
      phyla. The degree of this conservation tapers off, however, between land plants
      and algae. Plant snoRNAs are frequently organized in highly conserved spatial
      clusters. As a resource for further investigations we provide carefully curated
      and annotated alignments for each snoRNA family under investigation.

PMID- 27881083
TI  - Loss of maternal ANNEXIN A10 via a 34-kb deleted-type copy number variation is
      associated with embryonic mortality in Japanese Black cattle.
AB  - BACKGROUND: Conception is a fundamental trait for successful cattle reproduction.
      However, conception rates in Japanese Black cattle have been gradually declining
      over the last two decades. Although conception failures are mainly caused by
      embryonic mortality, the role of maternal genetic factors in the process remains
      unknown. Copy number variation (CNV), defined as large-scale genomic structural
      variants, contributes to several genetic disorders. To identify CNV associated
      with embryonic mortality in Japanese Black cattle, we evaluated embryonic
      mortality as a categorical trait with a threshold model and conducted a genome
      wide CNV association study for embryonic mortality using 791 animals. RESULTS: We
      identified a deleted-type CNV ranging from 378,127 to 412,061 bp on bovine
      chromosome 8, which was associated with embryonic mortality at 30-60 days after
      artificial insemination (AI). The CNV harbors exon 2 to 6 of ANNEXIN A10
      (ANXA10). Analysis of sequence traces from the CNV identified that 63 bp reads
      bridging the breakpoint were present on both sides of the CNV, indicating that
      the CNV was generated by non-allelic homologous recombination using the 63 bp
      homologous sequences. Western blot analysis showed that the CNV results in a null
      allele of ANXA10. This association was replicated using a sample population size
      of 2552 animals. To elucidate the function of ANXA10 in vivo, we generated Anxa10
      null mice using the CRISPR/Cas9 system. Crossbreeding experiments showed that
      litter size from crosses of both Anxa10 -/- and Anxa10 +/- females had fewer pups
      than did Anxa10 +/+ females, and embryos of Anxa10 -/- females died between
      implantation stages E4.5 and E12.5. These results indicate that loss of maternal
      Anxa10 causes embryonic mortality. CONCLUSIONS: This study identified a deleted
      type CNV encompassing ANXA10 in cows that was associated with embryonic mortality
      at 30-60 days after AI. Using a mouse model, we confirmed that litter sizes were
      smaller in crosses of both Anxa10 -/- and Anxa10 +/- females relative to those of
      wild females. These results indicate that ANXA10 is a maternal factor that is
      critical for embryo development.

PMID- 27881085
TI  - The Ebola Outbreak: Catalyzing a "Shift" in Global Health Governance?
AB  - BACKGROUND: As the 2014 Ebola virus disease outbreak (EVD) transitions to its
      post-endemic phase, its impact on the future of global public health,
      particularly the World Health Organization (WHO), is the subject of continued
      debate. Criticism of WHO's performance grew louder in the outbreak's wake,
      placing this international health UN-specialized agency in the difficult position
      of navigating a complex series of reform recommendations put forth by different
      stakeholders. Decisions on WHO governance reform and the broader role of the
      United Nations could very well shape the future landscape of 21st century global
      health and how the international community responds to health emergencies.
      DISCUSSION: In order to better understand the implications of the EVD outbreak on
      global health and infectious disease governance, this debate article critically
      examines a series of reports issued by four high-level commissions/panels
      convened to specifically assess WHO's performance post-Ebola. Collectively, these
      recommendations add increasing complexity to the urgent need for WHO reform, a
      process that the agency must carry out in order to maintain its legitimacy.
      Proposals that garnered strong support included the formation of an independent
      WHO Centre for Emergency Preparedness and Response, the urgent need to increase
      WHO infectious disease funding and capacity, and establishing better operational
      and policy coordination between WHO, UN agencies, and other global health
      partners. The recommendations also raise more fundamental questions about
      restructuring the global health architecture, and whether the UN should play a
      more active role in global health governance. Despite the need for a fully
      modernized WHO, reform proposals recently announced by WHO fail to achieve the
      "evolution" in global health governance needed in order to ensure that global
      society is adequately protected against the multifaceted and increasingly complex
      nature of modern public health emergencies. Instead, the lasting legacy of the
      EVD outbreak may be its foreshadowing of a governance "shift" in formal sharing
      of the complex responsibilities of global health, health security, outbreak
      response, and managing health emergencies to other international structures, most
      notably the United Nations. Only time will tell if the legacy of EVD will include
      a WHO that has the full support of the international community and is capable of
      leading human society in this brave new era of the globalization of infectious
      diseases.

PMID- 27881084
TI  - Assessing characteristics of RNA amplification methods for single cell RNA
      sequencing.
AB  - BACKGROUND: Recently, measurement of RNA at single cell resolution has yielded
      surprising insights. Methods for single-cell RNA sequencing (scRNA-seq) have
      received considerable attention, but the broad reliability of single cell methods
      and the factors governing their performance are still poorly known. RESULTS:
      Here, we conducted a large-scale control experiment to assess the transfer
      function of three scRNA-seq methods and factors modulating the function. All
      three methods detected greater than 70% of the expected number of genes and had a
      50% probability of detecting genes with abundance greater than 2 to 4 molecules.
      Despite the small number of molecules, sequencing depth significantly affected
      gene detection. While biases in detection and quantification were qualitatively
      similar across methods, the degree of bias differed, consistent with differences
      in molecular protocol. Measurement reliability increased with expression level
      for all methods and we conservatively estimate measurements to be quantitative at
      an expression level greater than ~5-10 molecules. CONCLUSIONS: Based on these
      extensive control studies, we propose that RNA-seq of single cells has come of
      age, yielding quantitative biological information.

PMID- 27881087
TI  - Intraspecific rearrangement of mitochondrial genome suggests the prevalence of
      the tandem duplication-random loss (TDLR) mechanism in Quasipaa boulengeri.
AB  - BACKGROUND: Tandem duplication followed by random loss (TDRL) is the most
      frequently invoked model to explain the diversity of gene rearrangements in
      metazoan mitogenomes. The initial stages of gene rearrangement are difficult to
      observe in nature, which limits our understanding of incipient duplication events
      and the subsequent process of random loss. Intraspecific gene reorganizations may
      represent intermediate states, and if so they potentially shed light on the
      evolutionary dynamics of TDRL. RESULTS: Nucleotide sequences in a hotspot of gene
      rearrangement in 28 populations of a single species of frog, Quasipaa boulengeri,
      provide such predicted intermediate states. Gene order and phylogenetic analyses
      support a single tandem duplication event and a step-by-step process of random
      loss. Intraspecific gene rearrangements are not commonly found through comparison
      of all mitochondrial DNA records of amphibians and squamate reptiles in GenBank.
      CONCLUSIONS: The intraspecific variation in Q. boulengeri provides insights into
      the rate of partial duplications and deletions within a mitogenome, and reveals
      that fixation and gene-distribution in mitogenomic reorganization is likely non
      adaptive.

PMID- 27881086
TI  - Lower-extremity resistance training on unstable surfaces improves proxies of
      muscle strength, power and balance in healthy older adults: a randomised control
      trial.
AB  - BACKGROUND: It is well documented that both balance and resistance training have
      the potential to mitigate intrinsic fall risk factors in older adults. However,
      knowledge about the effects of simultaneously executed balance and resistance
      training (i.e., resistance training conducted on unstable surfaces [URT]) on
      lower-extremity muscle strength, power and balance in older adults is
      insufficient. The objective of the present study was to compare the effects of
      machine-based stable resistance training (M-SRT) and two types of URT, i.e.,
      machine-based (M-URT) and free-weight URT (F-URT), on measures of lower-extremity
      muscle strength, power and balance in older adults. METHODS: Seventy-five healthy
      community-dwelling older adults aged 65-80 years, were assigned to three
      intervention groups: M-SRT, M-URT and F-URT. Over a period of ten weeks, all
      participants exercised two times per week with each session lasting ~60 min.
      Tests included assessment of leg muscle strength (e.g., maximal isometric leg
      extension strength), power (e.g., chair rise test) and balance (e.g., functional
      reach test), carried out before and after the training period. Furthermore,
      maximal training load of the squat-movement was assessed during the last training
      week. RESULTS: Maximal training load of the squat-movement was significantly
      lower in F-URT in comparison to M-SRT and M-URT. However, lower-extremity
      resistance training conducted on even and uneven surfaces meaningfully improved
      proxies of strength, power and balance in all groups. M-URT produced the greatest
      improvements in leg extension strength and F-URT in the chair rise test and
      functional reach test. CONCLUSION: Aside from two interaction effects, overall
      improvements in measures of lower-extremity muscle strength, power and balance
      were similar across training groups. Importantly, F-URT produced similar results
      with considerably lower training load as compared to M-SRT and M-URT. Concluding,
      F-URT seems an effective and safe alternative training program to mitigate
      intrinsic fall risk factors in older adults. TRIAL REGISTRATION: This trial has
      been registered with clinicaltrials.gov ( NCT02555033 ) on 09/18/2015.

PMID- 27881088
TI  - Perceived risk of tuberculosis infection among healthcare workers in Swaziland.
AB  - BACKGROUND: The incidence of tuberculosis (TB) in the Kingdom of Swaziland is
      extremely high. How healthcare workers (HCWs) in Swaziland perceive infection
      control (IC) measures for preventing TB transmission is unclear. This study aimed
      to determine perceived risk of TB infection in relation to IC measures among HCWs
      in three institutions of Swaziland. METHODS: A cross-sectional questionnaire
      survey was conducted in 2014. Demographic data and IC measures were collected
      from main and allied HCWs. RESULTS: In total, 186 HCWs (19 doctors, 99 nurses,
      and 68 allied HCWs) were enrolled. The multivariate logistic regression analyses
      revealed that nurses (OR = 39.87, 95% CI = 2.721-584.3) and other HCWs (OR
      =99.34, 95% CI = 7.469-1321) perceived a higher TB infection risk than did
      doctors. Moreover, HCWs working for <4 years at the TB department perceived a
      lower TB infection risk (OR = 0.099, 95% CI = 0.022-0.453). Availability of N95
      respirator masks (OR = 0.055, 95% CI = 0.005-0.586) and a designated sputum
      collection area (OR = 0.142, 95% CI = 0.037-0.545) also carried lower TB
      infection risks. CONCLUSION: This study depicts the current status of IC measures
      for TB infection in a high prevalence country. The results suggest that HCWs
      perceived a greater TB infection risk at inadequate environmental IC measures.

PMID- 27881089
TI  - Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A
      deficiency.
AB  - BACKGROUND: The WNT10A protein is critical for the development of ectodermal
      appendages. Variants in the WNT10A gene may be associated with a spectrum of
      ectodermal abnormalities including extensive tooth agenesis. METHODS: In seven
      patients with severe tooth agenesis we identified anomalies in primary dentition
      and additional ectodermal symptoms, and assessed WNT10A mutations by genetic
      analysis. RESULTS: Investigation of primary dentition revealed peg-shaped crowns
      of primary mandibular incisors and three individuals had agenesis of at least two
      primary teeth. The permanent dentition was severely affected in all individuals
      with a mean of 21 missing teeth. Primary teeth were most often present in
      positions were succedaneous teeth were missing. Furthermore, most existing molars
      had taurodontism. Light, brittle or coarse hair was reported in all seven
      individuals, hyperhidrosis of palms and soles in six individuals and nail
      anomalies in two individuals. The anomalies in primary dentition preceded most of
      the additional ectodermal symptoms. Genetic analysis revealed that all seven
      individuals were homozygous or compound heterozygous for WNT10A mutations
      resulting in C107X, E222X and F228I. CONCLUSIONS: We conclude that tooth agenesis
      and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of
      permanent dentition as well as ectodermal symptoms of varying severity may be
      predictors of bi-allelic WNT10A mutations of importance for diagnosis,
      counselling and follow-up.

PMID- 27881090
TI  - Genome-wide analysis of the TPX2 family proteins in Eucalyptus grandis.
AB  - BACKGROUND: The Xklp2 (TPX2) proteins belong to the microtubule-associated (MAP)
      family of proteins. All members of the family contain the conserved TPX2 motif,
      which can interact with microtubules, regulate microtubule dynamics or assist
      with different microtubule functions, for example, maintenance of cell morphology
      or regulation of cell growth and development. However, the role of members of the
      TPX family have not been studied in the model tree species Eucalyptus to date.
      Here, we report the identification of the members of the TPX2 family in
      Eucalyptus grandis (Eg) and analyse the expression patterns and functions of
      these genes. RESULTS: In present study, a comprehensive analysis of the plant
      TPX2 family proteins was performed. Phylogenetic analyses indicated that the
      genes can be classified into 6 distinct subfamilies. A genome-wide survey
      identified 12 members of the TPX2 family in the sequenced genome of Eucalyptus
      grandis. The basic genetic properties of the TPX2 family in Eucalyptus were
      analysed. Our results suggest that the TPX2 family proteins within different sub
      groups are relatively conserved but there are important differences between
      groups. Quantitative real-time PCR (qRT-PCR) was performed to confirm the
      expression levels of the genes in different tissues. The results showed that in
      the whole plant, the levels of EgWDL5 transcript are the highest, followed by
      those of EgWDL4. Compared with other tissues, the level of the EgMAP20 transcript
      is the highest in the root. Over-expression of EgMAP20 in Arabidopsis resulted in
      organ twisting. The cotyledon petioles showed left-handed twisting while the
      hypocotyl epidermal cells produced right-handed helical twisting. Finally,
      EgMAP20, EgWDL3 and EgWDL3L were all able to decorate microtubules. CONCLUSIONS:
      Plant TPX2 family proteins were systematically analysed using bioinformatics
      methods. There are 12 TPX2 family proteins in Eucalyptus. We have performed an
      initial characterization of the functions of several members of the TPX2 family.
      We found that the gene products are localized to the microtubule cytoskeleton.
      Our results lay the foundation for future efforts to reveal the biological
      significance of TPX2 family proteins in Eucalyptus.

PMID- 27881092
TI  - The relationship between in-hospital location and outcomes of care in patients
      diagnosed with dementia and/or delirium diagnoses: analysis of patient journey.
AB  - BACKGROUND: The discrepancy between the number of admissions and the allocation
      of hospital beds means that many patients admitted to hospital can be placed in
      units or wards other than that which specialise in the patient's primary health
      issue (home-ward). These patients are called 'outlier' patients. Risk factors and
      health system outcomes of hospital care for 'outlier' patients diagnosed with
      dementia and/or delirium are unknown. Therefore, the aim of this research was to
      examine patient journeys of people with dementia and/or delirium diagnoses, to
      identify risk factors for 'inlier' or 'outlier' status and patient or health
      system outcomes (consequences) of this status. METHODS: A retrospective,
      descriptive study compared patients who had dementia and/or delirium according to
      the proportion of time spent on the home ward i.e. 'inliers' or 'outliers'. Data
      from the patient journey database at Flinders Medical Centre (FMC), a public
      hospital in South Australia from 2007 and 2014 were extracted and analysed. The
      analysis was carried out on the patient journeys of people with a dementia and/or
      delirium diagnosis. RESULTS: When 6367 inpatient journeys with dementia and/or
      delirium within FMC were examined, the Emergency Department (ED) Length of Stay
      (LOS) after being admitted as inpatient was prolonged for 'outlier' patients
      compared to 'inlier' patients (OR: 1.068, 95% CI: 1.057-1.079, p = 0.000).
      However, the inpatient LOS for'outlier' patients was only marginally shorter than
      that of the 'inlier' patients (OR: 0.998, 95% CI: 0.998-0.998, p = 0.000). The
      chances of dying within 48 h of admission increased for 'outlier' patients (OR:
      1.973, 95% CI: 1.158-3.359, p = 0.012) and their Charlson co-morbidity Index was
      higher (OR: 1.059, 95% CI: 1.021-1.10, p = 0.002). Completion of discharge
      summaries within 2 days post-discharge for 'outlier' patients was compromised
      (OR: 1.754, 95% CI: 1.492-2.061, p = 0.000).Additionally, 'outlier' patients were
      more likely to be discharged to another hospital for other care types not offered
      at FMC (OR: 1.931, 95% CI: 1.559-2.391, p = 0.000). CONCLUSION: An examination of
      the patient journeys at FMC has determined that the health system outcomes for
      patients with dementia and/or delirium who are admitted outside of their home
      ward are affected by in-hospital location despite the homogenous nature of the
      study population.

PMID- 27881091
TI  - Conducting a large, multi-site survey about patients' views on broad consent:
      challenges and solutions.
AB  - BACKGROUND: As biobanks play an increasing role in the genomic research that will
      lead to precision medicine, input from diverse and large populations of patients
      in a variety of health care settings will be important in order to successfully
      carry out such studies. One important topic is participants' views towards
      consent and data sharing, especially since the 2011 Advanced Notice of Proposed
      Rulemaking (ANPRM), and subsequently the 2015 Notice of Proposed Rulemaking
      (NPRM) were issued by the Department of Health and Human Services (HHS) and
      Office of Science and Technology Policy (OSTP). These notices required that
      participants consent to research uses of their de-identified tissue samples and
      most clinical data, and allowing such consent be obtained in a one-time, open
      ended or "broad" fashion. Conducting a survey across multiple sites provides
      clear advantages to either a single site survey or using a large online database,
      and is a potentially powerful way of understanding the views of diverse
      populations on this topic. METHODS: A workgroup of the Electronic Medical Records
      and Genomics (eMERGE) Network, a national consortium of 9 sites (13 separate
      institutions, 11 clinical centers) supported by the National Human Genome
      Research Institute (NHGRI) that combines DNA biorepositories with electronic
      medical record (EMR) systems for large-scale genetic research, conducted a survey
      to understand patients' views on consent, sample and data sharing for future
      research, biobank governance, data protection, and return of research results.
      RESULTS: Working across 9 sites to design and conduct a national survey presented
      challenges in organization, meeting human subjects guidelines at each
      institution, and survey development and implementation. The challenges were met
      through a committee structure to address each aspect of the project with
      representatives from all sites. Each committee's output was integrated into the
      overall survey plan. A number of site-specific issues were successfully managed
      allowing the survey to be developed and implemented uniformly across 11 clinical
      centers. CONCLUSIONS: Conducting a survey across a number of institutions with
      different cultures and practices is a methodological and logistical challenge.
      With a clear infrastructure, collaborative attitudes, excellent lines of
      communication, and the right expertise, this can be accomplished successfully.

PMID- 27881094
TI  - Neutrophil-lymphocyte ratio is associated with arterial stiffness in patients
      with peritoneal dialysis.
AB  - BACKGROUND: Patients with peritoneal dialysis are in the persistent inflammation
      state and have elevated arterial stiffness. Neutrophil-lymphocyte ratio(NLR) is a
      new inflammatory marker in renal and cardiac disorders. Brachial-ankle pulse wave
      velocity (baPWV) is a non-invasive measurement, which is widely used as a
      surrogate marker of arterial stiffness. However, there is little evidence to show
      an association between NLR and baPWV in patients with peritoneal dialysis. The
      aim of this cross-section study was to investigate the relationship between NLR
      and arterial stiffness measured by baPWV in patients with peritoneal dialysis.
      METHODS: In this cross-section study, 101 patients with peritoneal dialysis were
      enrolled from January 2014 to June 2015. According to average baPWV level
      (1847.54 cm/s), the patients were categorized into two groups, low group and high
      group. baPWV, which reflects arterial stiffness, was calculated using the single
      point method. Clinical data were collected in details. NLR was calculated using
      complete blood count. Associations between NLR and baPWV were assessed using
      Pearson's correlation and linear regression analysis. RESULTS: The NLR was
      significantly lower in the low baPWV group than in the high baPWV group (p =
      0.03). There were positive correlations between baPWV and neutrophil count (r =
      0.24, p = 0.01) and NRL(r = 0.43, P < 0.01), and there was a negative correlation
      between baPWV and lymphocyte count (r = -0.23, p = 0.01). In addition, albumin,
      phosphorous and intact parathyroid hormone showed negative correlations with
      baPWV (r = -0.32, p < 0.01; r = -0.28, p < 0.01; r = -0.25, p = 0.01,
      respectively). Age and hsCRP showed positive correlations with baPWV (r = 0.47, p
      < 0.01; r = 0.25, p = 0.01). In multivariate analysis, NLR independently
      correlated with baPWV in patients with peritoneal dialysis (beta = 0.33, p <
      0.01), even after adjustment for various confounders. CONCLUSION: Our study
      suggests that NLR was an independently associated with arterial stiffness in
      patients with peritoneal dialysis. However, further prospective studies are
      needed to confirm cause-and-effect relationship between NLR and baPWV, and to
      investigate whether anti-inflammatory treatment could improve arterial stiffness
      in patients with peritoneal dialysis.

PMID- 27881093
TI  - Continuous quality improvement in nephrology: a systematic review.
AB  - BACKGROUND: Continuous quality improvement (CQI) has been successfully applied in
      business and engineering for over 60 years. While using CQI techniques within
      nephrology has received increased attention, little is known about where, and
      with what measure of success, CQI can be attributed to improving outcomes within
      nephrology care. This is particularly important as payors' focus on value-based
      healthcare and reimbursement is tied to achieving quality improvement thresholds.
      We conducted a systematic review of CQI applications in nephrology. METHODS:
      Studies were identified from PubMed, MEDLINE, Scopus, Web of Science, CINAHL,
      Google Scholar, ProQuest Dissertation Abstracts and sources of grey literature
      (i.e., available in print/electronic format but not controlled by commercial
      publishers) between January 1, 2004 and October 13, 2014. We developed a
      systematic evaluation protocol and pre-defined criteria for review. All citations
      were reviewed by two reviewers with disagreements resolved by consensus. RESULTS:
      We initially identified 468 publications; 40 were excluded as duplicates or not
      available/not in English. An additional 352 did not meet criteria for full review
      due to: 1. Not meeting criteria for inclusion = 196 (e.g., reviews, news
      articles, editorials) 2. Not nephrology-specific = 153, 3. Only available as
      abstracts = 3. Of 76 publications meeting criteria for full review, the majority
      [45 (61%)] focused on ESRD care. 74% explicitly stated use of specific CQI tools
      in their methods. The highest number of publications in a given year occurred in
      2011 with 12 (16%) articles. 89% of studies were found in biomedical and allied
      health journals and most studies were performed in North America (52%). Only one
      was randomized and controlled although not blinded. CONCLUSIONS: Despite calls
      for healthcare reform and funding to inspire innovative research, we found few
      high quality studies either rigorously evaluating the use of CQI in nephrology or
      reporting best practices. More rigorous research is needed to assess the
      mechanisms and attributes by which CQI impacts outcomes before there is further
      promotion of its use for improvement and reimbursement purposes.

PMID- 27881095
TI  - A regional consensus recommendation on brain atrophy as an outcome measure in
      multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease characterized
      by inflammatory and neurodegenerative processes leading to irreversible
      neurological impairment. Brain atrophy occurs early in the course of the disease
      at a rate greater than the general population. Brain volume loss (BVL) is
      associated with disability progression and cognitive impairment in patients with
      MS; hence its value as a potential target in monitoring and treating MS is
      discussed. METHODS: A group of MS neurologists and neuro-radiologists reviewed
      the current literature on brain atrophy and discussed the challenges in assessing
      and implementing brain atrophy measurements in clinical practice. The panel used
      a voting system to reach a consensus and the votes were counted for the proposed
      set of questions for cognitive and brain atrophy assessments. RESULTS: The panel
      of experts was able to identify recent studies, which demonstrated the
      correlation between BVL and future worsening of disability and cognition. The
      current evidence revealed that reduction of BVL could be achieved with different
      disease-modifying therapies (DMTs). BVL provided a better treatment and
      monitoring strategy when it is combined to the composite measures of "no evidence
      of disease activity" (NEDA). The panel recommended a set of cognitive assessment
      tools and MRI methods and software applications that may help in capturing and
      measuring the underlying MS pathology with high degree of specificity.
      CONCLUSION: BVL was considered to be a useful measurement to longitudinally
      assess disease progression and cognitive function in patients with MS. Brain
      atrophy measurement was recommended to be incorporated into the concept of NEDA.
      Consequently, a consensus recommendation was reached in anticipation for
      implementation of the use of cognitive assessment and brain atrophy measurements
      on a regional level.

PMID- 27881096
TI  - A step toward essential tremor gene discovery: identification of extreme
      phenotype and screening of HTRA2 and ANO3.
AB  - BACKGROUND: Essential tremor (ET) is characterized by a frequent family history.
      No monogenic form of ET has been identified. We aimed at exploring ET patients to
      identify distinct subgroups and facilitate the identification of ET genes. We
      tested for the presence of HTRA2 p.G399S, and ANO3 p. W490C, p. R484 W and p.
      S685G mutations. METHODS: Between June 2011 and November 2013, all consecutive
      patients suspected with ET were prospectively included in a prospective,
      monocentric study. Family history, age at onset (AAO), features of tremor,
      benefit of alcohol and drugs, electrophysiological recording findings were
      collected. Sanger sequencing was performed for HTRA2 and ANO3 mutations
      screening. RESULTS: Sixty eight patients were investigated. Fourteen diagnosed
      with psychogenic (5) or dystonic tremor (9) were excluded. Regarding the 54 ET
      patients, mean AAO was 48 years (6-77), and mean disease duration 15 years (1
      55). Bimodal distribution of AAO was consistent with phenotypic subgroups. In
      patients with AAO before 30 years, marked benefit of alcohol (p < 0.01) and ET
      family history (p < 0.01) were more frequent and the disease progression less
      severe (p < 0.0001). Neither HTRA2 nor ANO3 mutation were identified in our
      patients. CONCLUSIONS: Our data support that distinct ET phenotypic subgroups may
      be encountered. We recommend to study separately extreme phenotypes of ET,
      particularly autosomal dominant families with early AAO (<30 years) and marked
      benefit of alcohol, to facilitate the identification of ET genes.
      Electromyographic recording remains a support to distinguish ET from differential
      diagnosis. HTRA2 and ANO3 mutations are not common causes of ET.

PMID- 27881098
TI  - Genomic determination of minimum multi-locus sequence typing schemas to represent
      the genomic phylogeny of Mycoplasma hominis.
AB  - BACKGROUND: Mycoplasma hominis is an opportunistic human pathogen, associated
      with clinically diverse disease. Currently, there is no standardised method for
      typing M. hominis, which would aid in understanding pathogen epidemiology and
      transmission. Due to availability and costs of whole genome sequencing and the
      challenges in obtaining adequate M. hominis DNA, the use of whole genome sequence
      analysis to provide clinical guidance is unpractical for this bacterial species
      as well as other fastidious organisms. RESULTS: This study identified pan-genome
      set of 700 genes found to be present in four published reference genomes. A
      subset of 417 genes was identified to be core genome for 18 isolates and 1
      reference. Leave-one-out analysis of the core genes highlighted set of 48 genes
      that are required to recapture the original phylogenetic relationships observed
      using whole genome SNP analysis. Three 7-locus MLST schemas with high diversity
      index (97%) and low dN/dS ratios (0.1, 0.13, and 0.11) were derived that could be
      used to confer good discrimination between strains and could be of practical use
      in future studies direct on clinical specimens. CONCLUSIONS: The genes proposed
      in this study could be utilised to design a cost-effective and rapid PCR-based
      MLST assay that could be applied directly to clinical isolates, without prior
      isolation. This study includes additional genomic analysis revealing high levels
      of genetic heterogeneity among this species. This provides a novel and evidence
      based approach for the development of MLST schema that accurately represent
      genomic phylogeny for use in epidemiology and transmission studies.

PMID- 27881097
TI  - Ischaemic stroke and Clostridium septicum sepsis and meningitis in a patient with
      occult colon carcinoma - a case report and review of the literature.
AB  - BACKGROUND: Clostridium septicum is a rare cause of meningitis and brain abscess
      in children and adults. Gas production by the pathogen can lead to pneumocephalus
      and the overall mortality rate of Clostridium septicum CNS infection is as high
      as 74%. The most common entry site of the pathogen is the gastrointestinal tract.
      CASE PRESENTATION: We describe a 74-year-old man who presented with a left-sided
      cerebral infarction in the middle cerebral artery territory. In addition the
      patient showed signs of Systemic Inflammatory Response Syndrome and Disseminated
      Intravascular Coagulation. Examination of blood cultures and cerebrospinal fluid
      led to the diagnosis of sepsis and meningitis caused by Clostridium septicum.
      Despite appropriate antibiotic therapy the condition of the patient deteriorated
      rapidly and he died on day 2 after admission. Autopsy revealed a previously
      unknown adenocarcinoma of the colon ascendens as entry site of the pathogen.
      CONCLUSION: Clostridium septicum should be considered as potential pathogen in
      patients with sepsis and meningitis. Gram stain morphology in conjunction with
      severe sepsis can rapidly point into the direction of this pathogen. CNS
      infections manifest either as meningoencephalitis/cerebritis or as brain abscess.
      Entry site of the pathogen is almost uniquely the gastrointestinal tract. In
      adults more than 50% suffer from colorectal carcinoma, therefore survivors of
      Clostridium septicum infections should be examined for underlying occult
      colorectal malignancy.

PMID- 27881099
TI  - Predictors of HIV infection: a prospective HIV screening study in a Ugandan
      refugee settlement.
AB  - BACKGROUND: The instability faced by refugees may place them at increased risk of
      exposure to HIV infection. Nakivale Refugee Settlement in southwestern Uganda
      hosts 68,000 refugees from 11 countries, many with high HIV prevalence. We
      implemented an HIV screening program in Nakivale and examined factors associated
      with new HIV diagnosis. METHODS: From March 2013-November 2014, we offered free
      HIV screening to all clients in the Nakivale Health Center while they waited for
      their outpatient clinic visit. Clients included refugees and Ugandan nationals
      accessing services in the settlement. Prior to receiving the HIV test result,
      participants were surveyed to obtain demographic information including gender,
      marital status, travel time to reach clinic, refugee status, and history of prior
      HIV testing. We compared variables for HIV-infected and non-infected clients
      using Pearson's chi-square test, and used multivariable binomial regression
      models to identify predictors of HIV infection. RESULTS: During the HIV screening
      intervention period, 330 (4%) of 7766 individuals tested were identified as HIV
      infected. Refugees were one quarter as likely as Ugandan nationals to be HIV
      infected (aRR 0.27 [0.21, 0.34], p < 0.0001). Additionally, being female (aRR
      1.43 [1.14, 1.80], p = 0.002) and traveling more than 1 h to the clinic (aRR 1.39
      [1.11, 1.74], p = 0.003) increased the likelihood of being HIV-infected. Compared
      to individuals who were married or in a stable relationship, being
      divorced/separated/widowed increased the risk of being HIV-infected (aRR 2.41
      [1.88, 3.08], p < 0.0001), while being single reduced the risk (aRR 0.60 [0.41,
      0.86], p < 0.0001). Having been previously tested for HIV (aRR 0.59 [0.47, 0.74],
      p < 0.0001) also lowered the likelihood of being HIV-infected. CONCLUSIONS: In an
      HIV screening program in a refugee settlement in Uganda, Ugandan nationals are at
      higher risk of having HIV than refugees. The high HIV prevalence among clients
      seeking outpatient care, including Ugandan nationals and refugees, warrants
      enhanced HIV screening services in Nakivale and in the surrounding region.
      Findings from this research may be relevant for other refugee settlements in Sub
      Saharan Africa hosting populations with similar demographics, including the 9
      other refugee settlements in Uganda.

PMID- 27881100
TI  - High prevalence of non-steroidal anti-inflammatory drug use among acute kidney
      injury survivors in the southern community cohort study.
AB  - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and
      have been linked to acute kidney injury (AKI), chronic kidney disease (CKD) and
      cardiovascular disease (CVD). Patients who survive an AKI episode are at risk for
      future adverse kidney and cardiovascular outcomes. The objective of our study was
      to examine the prevalence and predictors of NSAID use among AKI survivors.
      METHODS: The Southern Community Cohort Study is a prospective study of low-income
      adults aged 40-79 in the southeastern US. Through linkage with Centers for
      Medicare and Medicaid Services, 826 participants with an AKI diagnosis (ICD-9
      584.5-584.9) at any age prior to cohort enrollment were identified. At baseline,
      data were collected on regular use of prescription and over-the-counter NSAIDs,
      as well as demographic, medical and other characteristics. Additional
      comorbidities were ascertained via linkage with CMS or the US Renal Data System.
      RESULTS: One hundred fifty-four AKI survivors (19%) reported regular NSAID use at
      cohort enrollment (52 prescription, 81 OTC, 21 both) and the percentage of NSAID
      users did not vary by time since AKI event. Over 58% of users were taking NSAIDS
      regularly both before and after their AKI event. Hypertension (83%), arthritis
      (71%), heart failure (44%), CKD (36%) and diabetes (35%) were prevalent among
      NSAID users. In a multivariable model, history of arthritis (OR: 3.00; 95% CI:
      1.92, 4.68) and acetaminophen use (OR: 2.43; 95% CI: 1.50, 3.93) were
      significantly associated with NSAID use, while prevalent CKD (OR: 0.63; 95% CI:
      0.41, 0.98) and diabetes (OR: 0.44; 95% CI: 0.29, 0.69) were significantly
      inversely associated. CONCLUSIONS: NSAID use among AKI survivors is common and
      highlights the need to understand physician and patient decision-making around
      NSAIDs and to develop effective strategies to reduce NSAID use in this vulnerable
      population.

PMID- 27881102
TI  - Associations of sedentary behavior and physical activity with physical
      measurements and dyslipidemia in school-age children: a cross-sectional study.
AB  - BACKGROUND: Physical activity and sedentary behavior are common factors
      influencing cardiovascular health. However, how school and leisure-time
      activity/sedentary behavior are associated with physical fitness and blood lipid
      levels in primary school children in consideration of gender disparity remains
      unclear. METHODS: Data was obtained from a health and nutrition survey on primary
      school children from nine areas in China. The association between physical
      activities/sedentary behaviors (school and leisure-time physical activity levels,
      screen time, and other sedentary behaviors) and anthropometric
      measurements/prevalence of dyslipidemia were examined by multilevel analysis (the
      individual level, class level, grade level, and investigation area level)
      adjusted for age, energy intake and family income. RESULTS: A total of 770
      participants (average age = 9.4 +/- 1.7 years) were included. Prevalence of
      dyslipidemia was 10.9%. Prevalence of dyslipidemia was associated with screen
      time in boys [OR = 3.04, 95% CI (1.24-7.45)] and inversely associated with
      leisure-time physical activity in boys [OR = 2.22, 95% CI (1.08-4.56)] and school
      time activity in girls [OR = 5.34, 95% CI (1.18-24.16)]. CONCLUSIONS: Physical
      activity-but not sedentary behavior-was significantly associated with
      dyslipidemia in both genders. Increasing leisure-time physical activity for boys
      and school-time physical activity for girls may be critical.

PMID- 27881101
TI  - Knowledge, barriers and facilitators of exercise in dialysis patients: a
      qualitative study of patients, staff and nephrologists.
AB  - BACKGROUND: Despite growing evidence on benefits of increased physical activity
      in hemodialysis (HD) patients and safety of intra-dialytic exercise, it is not
      part of standard clinical care, resulting in a missed opportunity to improve
      clinical outcomes in these patients. To develop a successful exercise program for
      HD patients, it is critical to understand patients', staff and nephrologists'
      knowledge, barriers, motivators and preferences for patient exercise. METHODS: In
      depth interviews were conducted with a purposive sample of HD patients, staff and
      nephrologists from 4 dialysis units. The data collection, analysis and
      interpretation followed Criteria for Reporting Qualitative Research guidelines.
      Using grounded theory, emergent themes were identified, discussed and organized
      into major themes and subthemes. RESULTS: We interviewed 16 in-center HD patients
      (mean age 60 years, 50% females, 63% blacks), 14 dialysis staff members (6
      nurses, 3 technicians, 2 dietitians, 1 social worker, 2 unit administrators) and
      6 nephrologists (50% females, 50% in private practice). Although majority of the
      participants viewed exercise as beneficial for overall health, most patients
      failed to recognize potential mental health benefits. Most commonly reported
      barriers to exercise were dialysis-related fatigue, comorbid health conditions
      and lack of motivation. Specifically for intra-dialytic exercise, participants
      expressed concern over safety and type of exercise, impact on staff workload and
      resistance to changing dialysis routine. One of the most important motivators
      identified was support from friends, family and health care providers. Specific
      recommendations for an intra-dialytic exercise program included building a
      culture of exercise in the dialysis unit, and providing an individualized
      engaging program that incorporates education and incentives for exercising.
      CONCLUSION: Patients, staff and nephrologists perceive a number of barriers to
      exercise, some of which may be modifiable. Participants desired an individualized
      intra-dialytic exercise program which incorporates education and motivation, and
      they provided a number of recommendations that should be considered when
      implementing such a program.

PMID- 27881103
TI  - Demonstration of early efficacy results of the delayed-release combination of
      doxylamine-pyridoxine for the treatment of nausea and vomiting of pregnancy.
AB  - BACKGROUND: Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting
      mothers. In April 2013 the FDA approved the delayed-release combination of
      doxylamine succinate and pyridoxine hydrochloride (Diclegis(r)) for NVP, based in
      part, on the results of a phase III randomized trial demonstrating the efficacy
      of this drug combination [study drug marketed under the trade name Diclectin(r)
      in Canada and Diclegis(r) in the United States] compared to placebo in pregnant
      women. Study drug dosing occurred for 14 days, which is substantially longer than
      what has been performed in similar studies. The objective of this study was to
      evaluate, through secondary analysis, whether the primary measure of efficacy can
      be demonstrated after five days of treatment. METHODS: Women suffering from NVP
      were randomized to receive Diclegis(r) (n = 131) or placebo (n = 125) for 14 days
      at doses ranging from two to four tablets a day, based on a pre-specified
      titration protocol. The primary efficacy endpoint was the change in the validated
      Pregnancy-Unique Quantification of Emesis (PUQE) score at baseline versus Day 15
      between Diclegis(r)-treated and placebo-treated women. For the present study, the
      change in PUQE score between baseline and Day 15 (end of the study) was compared
      to the changes observed for Days 3, 4, and 5. RESULTS: The use of delayed-release
      doxylamine succinate and pyridoxine hydrochloride tablets show improved NVP
      symptom control as compared to placebo on Days 3,4 and 5, with sustained efficacy
      until the end of the trial. CONCLUSION: A four day study drug dosing trial with
      Diclegis(r) is sufficient to document efficacy, as the results are similar to
      those achieved after 14 study drug dosing days. The benefit seen at the earlier
      time validates drug efficacy and minimizes the natural course of improvement.
      TRIAL REGISTRATION: CTR No. NCT006 14445 2007.

PMID- 27881104
TI  - Provider adherence to first antenatal care guidelines and risk of pregnancy
      complications in public sector facilities: a Ghanaian cohort study.
AB  - BACKGROUND: Guideline utilization aims at improvement in quality of care and
      better health outcomes. The objective of the current study was to determine the
      effect of provider complete adherence to the first antenatal care guidelines on
      the risk of maternal and neonatal complications in a low resource setting.
      METHODS: Women delivering in 11 health facilities in the Greater Accra region of
      Ghana were recruited into a cohort study. Their first antenatal visit records
      were reviewed to assess providers' adherence to the guidelines, using a thirteen
      point checklist. Information on their socio-demographic characteristics and
      previous pregnancy history was collected. Participants were followed up for 6
      weeks post-partum to complete data collection on outcomes. The incidence of
      maternal and neonatal complications was estimated. The effects of complete
      adherence on risk of maternal and neonatal complications were estimated and
      expressed as relative risks (RRs) with their 95% confidence intervals (CI)
      adjusted for a potential clustering effect of health facilities. RESULTS:
      Overall, 926 women were followed up to 6 weeks post-partum. Mean age (SD) of
      participants was 28.2 (5.4) years. Complete adherence to guidelines pertained to
      the care of 48.5% of women. Incidence of preterm deliveries, low birth weight,
      stillbirths and neonatal mortality were 5.3, 6.1, 0.4 and 1.4% respectively.
      Complete adherence to the guidelines decreased risk of any neonatal complication
      [0.72 (0.65-0.93); p = 0.01] and delivery complication [0.66 (0.44-0.99), p =
      0.04]. CONCLUSION: Complete provider adherence to antenatal care guidelines at
      first antenatal visit influences delivery and neonatal outcomes. While there is
      the need to explore and understand explanatory mechanisms for these observations,
      programs that promote complete adherence to guidelines will improve the pregnancy
      outcomes.

PMID- 27881105
TI  - Open, trusting relationships underpin safety in rural maternity a hermeneutic
      phenomenology study.
AB  - BACKGROUND: There are interwoven personal, professional and organisational
      relationships to be navigated in maternity in all regions. In rural regions
      relationships are integral to safe maternity care. Yet there is a paucity of
      research on how relationships influence safety and nurture satisfying experiences
      for rural maternity care providers and mothers and families in these regions.
      This paper draws attention to how these relationships matter. METHODS: This
      research is informed by hermeneutic phenomenology drawing on Heidegger and
      Gadamer. Thirteen participants were recruited via purposeful sampling and asked
      to share their experiences of rural maternity care in recorded unstructured in
      depth interviews. Participants were women and health care providers living and
      working in rural regions. Recordings were transcribed and data interpretively
      analysed until a plausible and trustworthy thematic pattern emerged. RESULTS:
      Throughout the data the relational nature of rural living surfaced as an
      interweaving tapestry of connectivity. Relationships in rural maternity are
      revealed in myriad ways: for some optimal relationships, for others feeling
      isolated, living with discord and professional disharmony. Professional
      misunderstandings undermine relationships. Rural maternity can become
      unsustainable and unsettling when relationships break down leading to unsafeness.
      CONCLUSIONS: This study reveals how relationships are an important and vital
      aspect to the lived-experience of rural maternity care. Relationships are founded
      on mutual understanding and attuned to trust matter. These relationships are
      forged over time and keep childbirth safe and enable maternity care providers to
      work sustainably. Yet hidden unspoken pre-understandings of individuals and
      groups build tension in relationships leading to discord. Trust builds healthy
      rural communities of practice within which everyone can flourish, feel accepted,
      supported and safe. This is facilitated by collaborative learning activities and
      open respectful communication founded on what matters most (safe positive
      childbirth) whilst appreciating and acknowledging professional and personal
      differences.

PMID- 27881106
TI  - A pragmatic randomised multi-centre trial of multifamily and single family
      therapy for adolescent anorexia nervosa.
AB  - BACKGROUND: Considerable progress has been made in recent years in developing
      effective treatments for child and adolescent anorexia nervosa, with a general
      consensus in the field that eating disorders focussed family therapy (often
      referred to as Maudsley Family Therapy or Family Based Treatment) currently
      offers the most promising outcomes. Nevertheless, a significant number do not
      respond well and additional treatment developments are needed to improve
      outcomes. Multifamily therapy is a promising treatment that has attracted
      considerable interest and we report the results of the first randomised
      controlled trial of multifamily therapy for adolescent anorexia nervosa. METHODS:
      The study was a pragmatic multicentre randomised controlled superiority trial
      comparing two outpatient eating disorder focussed family interventions -
      multifamily therapy (MFT-AN) and single family therapy (FT-AN). A total of 169
      adolescents with a DSM-IV diagnosis of anorexia nervosa or eating disorder not
      otherwise specified (restricting type) were randomised to the two treatments
      using computer generated blocks of random sizes to ensure balanced numbers in the
      trial arms. Independent assessors, blind to the allocation, completed evaluations
      at baseline, 3 months, 12 months (end of treatment) and 18 months. RESULTS: Both
      treatment groups showed clinically significant improvements with just under 60%
      achieving a good or intermediate outcome (on the Morgan-Russell scales) at the
      end of treatment in the FT-AN group and more than 75% in the MFT-AN group - a
      statistically significant benefit in favour of the multifamily intervention (OR =
      2.55 95%; CI 1.17, 5.52; p = 0.019). At follow-up (18 months post baseline) there
      was relatively little change compared to end of treatment although the difference
      in primary outcome between the treatments was no longer statistically
      significant. Clinically significant gains in weight were accompanied by
      improvements in mood and eating disorder psychopathology. Approximately half the
      patients in FT-AN and nearly 60% of those in MFT-AN had started menstruating.
      CONCLUSIONS: This study confirms previous research findings demonstrating the
      effectiveness of eating disorder focused family therapy and highlights the
      additional benefits of bringing together groups of families that maximises the
      use of family resources and mutual support leading to improved outcomes. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN11275465 ; Registered 29 January
      2007 (retrospectively registered).

PMID- 27881108
TI  - Study protocol for a non-inferiority trial of a blended smoking cessation
      treatment versus face-to-face treatment (LiveSmokefree-Study).
AB  - BACKGROUND: Smoking cessation can significantly reduce the risk of developing
      smoking-related diseases. Several face-to-face and web-based treatments have
      shown to be effective. Blending of web-based and face-to-face treatment is
      expected to improve smoking cessation treatment. The primary objective of this
      study is to compare the prolonged abstinence rate of the blended smoking
      cessation treatment with the face-to-face treatment. Secondary objectives are to
      assess the benefits of blended treatment in terms of cost effectiveness and
      patient satisfaction, and to identify mechanisms underlying successful smoking
      cessation. METHODS/DESIGN: This study will be a single-center randomized
      controlled non-inferiority-trial with parallel group design. Patients (n = 344)
      will be randomly assigned to either the blended or the face-to-face group. Both
      treatments will consist of ten sessions with equal content held within 6 months.
      In the blended treatment five out of ten sessions will be delivered online. The
      treatments will cover the majority of behavior change techniques that are
      evidence-based within smoking cessation counseling. All face-to-face sessions in
      both treatments will take place at the outpatient smoking cessation clinic of a
      hospital. The primary outcome parameter will be biochemically validated prolonged
      abstinence at 15 months from the start of the smoking cessation treatment.
      DISCUSSION: This RCT will be the first study to examine the effectiveness of a
      blended smoking cessation treatment. It will also be the first study to explore
      patient satisfaction, adherence, cost-effectiveness, and the clinically relevant
      influencing factors of a blended smoking cessation treatment. The findings of
      this RCT are expected to substantially strengthen the base of evidence available
      to inform the development and delivery of smoking cessation treatment. TRIAL
      REGISTRATION: Nederlands Trialregister NTR5113 . Registered 24 March 2015.

PMID- 27881107
TI  - Risk of repeated self-harm and associated factors in children, adolescents and
      young adults.
AB  - BACKGROUND: Repeated self-harm represents the single strongest risk factor for
      suicide. To date no study with full national coverage has examined the pattern of
      hospital repeated presentations due to self-harm among young people. METHODS:
      Data on consecutive self-harm presentations were obtained from the National Self
      Harm Registry Ireland. Socio-demographic and behavioural characteristics of
      individuals aged 10-29 years who presented with self-harm to emergency
      departments in Ireland (2007-2014) were analysed. Risk of long-term repetition
      was assessed using survival analysis and time differences between the order of
      presentations using generalised estimating equation analysis. RESULTS: The total
      sample comprised 28,700 individuals involving 42,642 presentations. Intentional
      drug overdose was the most prevalent method (57.9%). Repetition of self-harm
      occurred in 19.2% of individuals during the first year following a first
      presentation, of whom the majority (62.7%) engaged in one repeated act. Overall,
      the risk of repeated self-harm was similar between males and females. However, in
      the 20-24-year-old age group males were at higher risk than females. Those who
      used self-cutting were at higher risk for repetition than those who used
      intentional drug overdose, particularly among females. Age was associated with
      repetition only among females, in particular adolescents (15-19 years old) were
      at higher risk than young emerging adults (20-24 years old). Repeated self-harm
      risk increased significantly with the number of previous self-harm episodes. Time
      differences between first self-harm presentations were detected. Time between
      second and third presentation increased compared to time between first and second
      presentation among low frequency repeaters (patients with 3 presentations only
      within 1 year following a first presentation). The same time period decreased
      among high frequency repeaters (patients with at least 4 to more than 30
      presentations). CONCLUSION: Young people with the highest risk for repeated self
      harm were 15-19-year-old females and 20-24-year-old males. Self-cutting was the
      method associated with the highest risk of self-harm repetition. Time between
      first self-harm presentations represents an indicator of subsequent repetition.
      To prevent risk of repeated self-harm in young people, all individuals presenting
      at emergency departments due to self-harm should be provided with a risk
      assessment including psychosocial characteristics, history of self-harm and time
      between first presentations.

PMID- 27881109
TI  - Anti-tumor effects of Abnormal Savda Munziq on the transplanted cervical cancer
      (U27) mouse model.
AB  - BACKGROUND: Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has
      shown anti-tumour properties in vitro. it was showed that total flavonoids of
      ASMq could inhibit the proliferation and enhance the antioxidant ability of human
      cervix cancer HeLa cell. This study attempts to confirm these effects on the
      transplanted cervical cancer (U27) mouse model in vivo. METHODS: Forty eight
      Kunming mice were randomly divided in to six groups: normal control group
      (Control group), U27 tumor model group (Model group), cyclophosphamide
      administration group (CTX group),low-dose ASMq group (ASMq.L group), medium-dose
      ASMq group (ASMq.M group), and high-dose ASMq group (ASMq.H group). The five
      groups except normal control group transplanted with cervical cancer (U27) cells.
      We observed mice tumor inhibition rate and conducted the histopathological
      analysisUsing the western blot assay, the expression of TGF-beta1 and TNF-alpha
      protein in transplanted cervical cancer U27 tumor tissue were detected. RESULTS:
      The tumor inhibition rates of CTX group, ASMq.L group, ASMq.M group, and ASMq.H
      group were 72.21, 31.27, 60.53 and 51.94% respectively, has obvious antitumor
      effect. ASMq significantly promote the spleen tlymphocyte proliferation of
      transplanted cervical cancer U27 mice. Invasive growth and diffusion rate in
      tumor tissue were accelerate in the transplanted cervical cancer U27 model group.
      Tumor tissue necrosis of tumor cells are smaller in the medium, high dosage
      group. Compared with the U27 model group, the expression levels of TGF-beta1
      protein and TNF-alpha protein expression exhibited statistically significant
      decreased in the mice tumor tissues in the CTX administration group and the ASMq
      administration group. CONCLUSIONS: ASMq has some antitumor effects on U27 model
      mice in vivo, The effects are achieved not only by improving the immune function
      of U27 model mice, but also by inhibiting the expression levels of TGF-beta1
      protein while promoting the expression levels of TNF-alpha protein.

PMID- 27881110
TI  - Prevalence of chronic kidney disease in patients with chronic obstructive
      pulmonary disease: a systematic review and meta-analysis.
AB  - BACKGROUND: The incidence and prevalence of chronic kidney disease (CKD) continue
      to rise worldwide. Increasing age, diabetes, hypertension, and cigarette smoking
      are well-recognized risk factors for CKD. Chronic obstructive pulmonary disease
      (COPD) is characterized by chronic airway inflammation leading to airway
      obstruction and parenchymal lung destruction. Due to some of the common
      pathogenic mechanisms, COPD has been associated with increased prevalence of CKD.
      METHODS: Systematic review of medical literature reporting the incidence and
      prevalence of CKD in patients with COPD using the Cochrane Collaboration
      Methodology, and conduct meta-analysis to study the cumulative effect of the
      eligible studies. We searched Medline via Ovid, PubMed, EMBASE and ISI Web of
      Science databases from 1950 through May, 2016. We included prospective and
      retrospective observational studies that reported the prevalence of CKD in
      patients with COPD. RESULTS: Our search resulted in 19 eligible studies of which
      9 have been included in the meta-analysis. The definition of CKD was uniform
      across all the studies included in analysis. COPD was found to be associated with
      CKD in the included epidemiological studies conducted in many countries. Our meta
      analysis showed that COPD was found to be associated with a significantly
      increased prevalence of CKD (Odds Ratio [OR] = 2.20; 95% Confidence Interval [CI]
      1.83, 2.65). STUDY LIMITATIONS: Studies included are observational studies.
      However, given the nature of our research question there is no possibility to
      perform a randomized control trial. CONCLUSIONS: Patients with COPD have
      increased odds of developing CKD. Future research should investigate the
      pathophysiological mechanism behind this association, which may lead to better
      outcomes.

PMID- 27881111
TI  - Fluid signal changes around the knee on MRI are associated with increased volumes
      of subcutaneous fat: a case-control study.
AB  - BACKGROUND: Fluid in the subcutaneous fat is a common finding anterior to the
      knee on MRI. This may be caused by chronic low-grade shearing injuries in
      patients who are overweight. The purpose of this study was to determine if there
      is a difference in the amount of subcutaneous fat around the knee between
      patients with these appearances and controls. METHODS: This was a retrospective
      case-control study. Following a sample size calculation on pilot data, eighteen
      sequential patients demonstrating hyper-intense subcutaneous signal changes
      around the knee on fat-saturated T2-weighted MRI were identified from PACS (18
      females, mean age 45, range 31-62). Age and gender-matched patients without
      abnormal T2 MR signal changes were selected. Two observers independently drew
      regions of interest representing cross-sectional areas of bone and fat. The
      location of T2 signal hyper-intense lesions was characterized by consensus.
      RESULTS: Inter and intra-rater intraclass reproducibility was "excellent" (ICC >
      0.8). The mean cross-sectional area of bone for patients with T2 hyper-intense
      lesions was 31.79cm2 (SD 2.57) and for controls 30.11cm2 (SD 3.20) which was not
      significantly different (p = 0.09). The median cross-sectional area of fat for
      the study group was 62.29cm2 (IQR 57.1-66.5) and for controls was 32.77cm2 (IQR
      24.8-32.3) which was significantly different (p < 0.0001). Consensus agreement
      demonstrated all T2 hyper-intense lesions were anterior to the knee extensor
      mechanism. CONCLUSION: Subcutaneous fluid around the knee is associated with an
      increased amount of subcutaneous fat, anterior to the knee extensor mechanism.
      This may be caused by shearing injuries in fat with reduced elasticity associated
      with metabolic syndrome.

PMID- 27881112
TI  - Photoprotective potential in some medicinal plants used to treat skin diseases in
      Sri Lanka.
AB  - BACKGROUND: The constant exposure to solar ultraviolet radiation (UV) has a
      variety of harmful effects on human health. Although synthetic sunscreen products
      have been introduced as a preventive/therapeutic strategy, with the realization
      of their adverse side effects, the recent trend is to search for human friendly
      alternative formulations especially of plant origin. Therefore, the present study
      focuses on evaluation of photoprotective activity of aqueous extracts (1 mg/ml)
      of eleven medicinal plants in Sri Lanka that have been widely employed in
      traditional medicine as treatment options for various skin diseases and to
      improve the complexion. METHODS: For the determination of UV filtering potential
      of the extracts, UV absorption was measured and the sun protection factor (SPF)
      was calculated according the Mansur equation. The antioxidant activity was
      evaluated by DPPH and ABTS assays. RESULTS: Among the extracts, Atalantia
      ceylanica, Hibiscus furcatus, Leucas zeylanica, Mollugo cerviana, Olax zeylanica
      and Ophiorrhiza mungos have displayed SPF value >= 25, which are even higher than
      two commercial photoprotective creams used as reference compounds. L. zeylanica
      and O. mungos have displayed a high UV absorbance in 260-350 nm range indicating
      their potential of being broad spectrum sunscreens. In addition, the extract of
      O. mungos was found to be photostable, without any significant reduction in the
      SPF after exposure to direct solar radiation for 21 days. DPPH assay and the ABTS
      assay revealed that the extracts possess high antioxidant activity. CONCLUSION:
      The results of the present study suggest that the presence of secondary
      metabolites with antioxidant property could be responsible for the high UV
      absorbance. Our findings would offer an exciting avenue for further research
      towards the development of herbal cosmetics.

PMID- 27881113
TI  - Psychotherapy integration under scrutiny: investigating the impact of integrating
      emotion-focused components into a CBT-based approach: a study protocol of a
      randomized controlled trial.
AB  - BACKGROUND: This currently recruiting randomized controlled trial investigates
      the effects of integrating components of Emotion-Focused Therapy (EFT) into
      Psychological Therapy (PT), an integrative form of cognitive-behavioral therapy
      in a manner that is directly mirroring common integrative practice in the sense
      of assimilative integration. Aims of the study are to understand how both, an
      existing therapy approach as well as the elements to be integrated, are affected
      by the integration and to clarify the role of emotional processing as a mediator
      of therapy outcome. METHODS: A total of 130 adults with a diagnosed unipolar
      depressive, anxiety or adjustment disorder (seeking treatment at a psychotherapy
      outpatient clinic) are randomized to either treatment as usual (PT) with
      integrated emotion-focused components (TAU + EFT) or PT (TAU). Primary outcome
      variables are psychopathology and symptom severity at the end of therapy and at
      follow up; secondary outcome variables are interpersonal problems, psychological
      wellbeing, quality of life, attainment of individual therapy goals, and emotional
      competency. Furthermore, process variables such as the quality of the therapeutic
      relationship are studied as well as aptitude-treatment interactions. Variables
      are assessed at baseline, after 8 and 16 sessions, at the end of therapy, after
      25 +/- 3 sessions, and at 6, 12 and 36 month follow-up. Underlying mechanisms of
      change are investigated. Statistical analyses will be conducted using the
      appropriate multilevel approaches, mainly two-level regression and growth
      analysis. DISCUSSION: The results of this study will indicate whether the
      integration of emotion-focused elements into treatment as usual increases the
      effectiveness of Psychological Therapy. If advantages are found, which may be
      limited to particular variables or subgroups of patients, recommendations for a
      systematic integration, and caveats if also disadvantages are detected, can be
      formulated. On a more abstract level, a cognitive behavioral (represented by PT)
      and humanistic/experiential (represented by EFT) approach will be integrated. It
      must be emphasized that mimicking common practice in the development and
      continued education of psychotherapists, EFT is not integrated as a whole, but
      only elements of EFT that are considered particularly important, and can be
      trained in an 8-day training plus supervision of therapies. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02822443 , 22 June 2016, retrospectively registered.

PMID- 27881114
TI  - Hypersensitivity reactions to metal implants: laboratory options.
AB  - BACKGROUND: All implant compounds undergo an electrochemical process when in
      contact with biological fluids, as well as mechanical corrosion due to abrasive
      wear, with production of metal debris that may inhibit repair processes. None of
      the commonly-used methods can diagnose implant allergies when used singly,
      therefore a panel of tests should be performed on allergic patients as pre
      operative screening, or when a postoperative metal sensitisation is suspected.
      METHODS: We analysed patients with painful prostheses and subjects prone to
      allergies using the Patch Test in comparison with the Lymphocyte Transformation
      Test. Cytokine production was evaluated to identify prognostic markers for early
      diagnosis of aseptic loosening. Metal debris endocytosis and cytoskeletal
      rearrangement was visualised by confocal microscopy. RESULTS: Our results
      demonstrate that the Lymphocyte Transformation Test can identify patients who
      have a predisposition to develop allergic reactions and can confirm the diagnosis
      of hypersensitivity in patients with painful prostheses. The prevalence of a Th2
      cytokine pattern may be used to identify predisposition to the development of
      allergic diseases, while the selective presence of osteoclastogenic cytokines may
      be used as predictor of a negative outcome in patients with painful prosthesis.
      The hypothesis of the prognostic value of these cytokines as early markers of
      aseptic loosening is attractive, but its confirmation would require extensive
      testing. CONCLUSIONS: The Lymphocyte Transformation Test is the most suitable
      method for testing systemic allergies. We suggest that the combined use of the
      Patch Test and the Lymphocyte Transformation Test, associated with cytokine
      detection in selected patients, could provide a useful tool for preventive
      evaluation of immune reactivity in patients undergoing primary joint replacement
      surgery, and for clinical monitoring of the possible onset of a metal
      sensitization in patients with implanted devices.

PMID- 27881115
TI  - Intestinal polyparasitism with special emphasis to soil-transmitted helminths
      among residents around Gilgel Gibe Dam, Southwest Ethiopia: a community based
      survey.
AB  - BACKGROUND: One third of the world population is estimated to be infected with
      intestinal parasites. The most affected people are children and the poor people
      living in tropics and subtropics. Polyparasitism (the concurrent infection with
      multiple intestinal parasite species) is found to be the norm among the same
      population although accurate estimate of its magnitude is unknown. It was found
      that polyparasitism might have a greater impact on morbidity than single species
      infection which might also increase susceptibility to other infections.
      Therefore, this study aimed at determining the prevalence and distribution of
      intestinal polyparasitism with special emphasis on Soil-Transmitted Helminths
      (STH) among residents around Gilgel Gibe dam located in Jimma zone of Oromia
      regional state, Ethiopia. METHODS: A total of 1,021 participants were recruited
      in this study and provided stool samples for parasitological examination. Direct
      wet mount and Kato-Katz techniques were employed for stool examination. Pearson
      chi-square test was employed to assess the association of infection status and
      polyparasitism with gender and age group of the study participants. RESULTS: Five
      hundred thirty two individuals were infected with at least one parasite,
      providing the overall prevalence of 52.1%. Among positive individuals, 405
      (76.1%), 114 (21.4%), and 13 (2.5%) individuals were infected with only one, two
      and three species of parasites, respectively. The overall prevalence of
      intestinal polyparasitism observed among the study participants was 12.4%
      (127/1,021). The predominant STH was hookworm, with a prevalence of 44.1%.
      Hookworm and Ascaris lumbricoides were the most frequently recorded combination
      in cases of polyparasitic infection. The study revealed that there was no
      significant difference in the distribution of polyparasitism with regard to age
      group and sex of the study participants (p > 0.05). CONCLUSION: The study
      indicated the presence of high prevalence of parasites as well as distribution of
      polyparasitism in the area. Moreover, the detection of Schistosoma mansoni in the
      community living within close proximity of the newly constructed dam would be
      taken as an indication of future risk factor. Further investigation on the
      predictors of polyparasitism and the assessment of effects of polyparasitism on
      the population are needed. Finally, there is a need to undertake integrated
      control strategies which involve improved sanitation, health education and
      chemotherapy that targets the whole community instead of only certain segments of
      populations.

PMID- 27881116
TI  - Concurrent agreement between an anthropometric model to predict thigh volume and
      dual-energy X-Ray absorptiometry assessment in female volleyball players aged 14
      18 years.
AB  - BACKGROUND: A variety of performance outputs are strongly determined by lower
      limbs volume and composition in children and adolescents. The current study aimed
      to examine the validity of thigh volume (TV) estimated by anthropometry in late
      adolescent female volleyball players. Dual-energy X-ray absorptiometry (DXA)
      measures were used as the reference method. METHODS: Total and regional body
      composition was assessed with a Lunar DPX NT/Pro/MD+/Duo/Bravo scanner in a cross
      sectional sample of 42 Portuguese female volleyball players aged 14-18 years
      (165.2 +/- 0.9 cm; 61.1 +/- 1.4 kg). TV was estimated with the reference method
      (TV-DXA) and with the anthropometric method (TV-ANTH). Agreement between
      procedures was assessed with Deming regression. The analysis also considered a
      calibration of the anthropometric approach. RESULTS: The equation that best
      predicted TV-DXA was: -0.899 + 0.876 * log10 (body mass) + 0.113 * log10 (TV
      ANTH). This new model (NM) was validated using the predicted residual sum of
      squares (PRESS) method (R2PRESS = 0.838). Correlation between the reference
      method and the NM was 0.934 (95%CI: 0.880-0.964, Sy?x = 0.325 L). CONCLUSIONS: A
      new and accurate anthropometric method to estimate TV in adolescent female
      volleyball players was obtained from the equation of Jones and Pearson alongside
      with adjustments for body mass.

PMID- 27881117
TI  - Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein
      tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic
      application.
AB  - BACKGROUND: The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is
      one of the immunodominant autoantigens involved in the autoimmune attack to the
      beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete
      and original process for the production and recovery of the properly folded
      intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli
      GI698 and GI724 strains. We have also carried out the biochemical and
      immunochemical characterization of TrxIA-2icand design variants of non
      radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA
      2A). RESULTS: The main findings can be summarized in the following statements: i)
      TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ~ 10 mg of
      highly pure TrxIA-2ic/L of culture medium by a single step purification by
      affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could
      be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry,
      iii) TrxIA-2ic was properly identified by western blot and mass spectrometric
      analysis of proteolytic digestions (63.25 % total coverage), iv) excellent
      immunochemical behavior of properly folded full TrxIA-2ic was legitimized by
      inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian
      Type 1 Diabetic patients, v) great stability over time was found under proper
      storage conditions and vi) low cost and environmentally harmless ELISA methods
      for IA-2A assessment were developed, with colorimetric or chemiluminescent
      detection. CONCLUSIONS: E. coli GI724 strain emerged as a handy source of
      recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion
      protein, adequately validated and applicable to the development of innovative and
      cost-effective immunoassays for IA-2A detection in most laboratories.

PMID- 27881118
TI  - Electrolyte disorders and aging: risk factors for delirium in patients undergoing
      orthopedic surgeries.
AB  - BACKGROUND: At present, the exact mechanism of postoperative delirium has not
      been elucidated. The purpose of this study was to analyze the incidence of
      delirium in patients undergoing orthopedic surgeries and to explore possible
      related factors. METHODS: This is a retrospective study. We used 582 patients who
      had undergone orthopedic surgery between January 2011 and December 2014. The
      surgeries consisted of 155 cases of internal fixation for intertrochanteric
      fracture (IFIF), 128 cases of femoral head replacement (FHR), 169 cases of total
      hip arthroplasty (THA) and 130 cases of total knee arthroplasty (TKA). Among the
      582 patients, 75 developed postoperative delirium (an incidence of 12.9%). The
      demographics of the patients, which included age, gender, operation duration and
      blood loss, were statistically analyzed with univariate logistic regression
      analysis and then multivariate logistic regression. To investigate the influences
      of different electrolytes disorders for postoperative delirium, the Chi-square
      test was used. RESULTS: Multivariate logistic regression analysis indicated that
      postoperative delirium incidence in patients aged 70-79 years and in patients
      aged >=80 years was higher than that in patients aged <70 years, odds ratio (OR)
      values were 6.33 and 26.37, respectively. In addition, the incidence of
      postoperative delirium in the group of patients with electrolyte disorders was
      higher than that in the normal group (OR, 2.38). There were statistically
      significant differences between the delirium group and the non-delirium group in
      the incidences of the sodium and calcium disorders. CONCLUSIONS: Aging and
      postoperative electrolyte disorders (hyponatremia and hypocalcemia) are risk
      factors for postoperative delirium in patients undergoing orthopedic surgeries.

PMID- 27881119
TI  - Antibacterial and antifungal potentials of the solvents extracts from Eryngium
      caeruleum, Notholirion thomsonianum and Allium consanguineum.
AB  - BACKGROUND: Herbal medicines have long been used for various ailments in various
      societies and natural bioactive compounds are gaining more and more importance
      due to various factors. In this context, three plant species i.e., Eryngium
      caeruleum, Notholirion thomsonianum and Allium consanguineum have been aimed for
      the scientific verification of their purported traditional uses against various
      infectious diseases. METHODS: In this study, three plants were assayed for
      antibacterial and antifungal potentials. The antibacterial investigations were
      performed via well diffusion method and nutrient broth dilution method. The
      bacterial strains used in the study were Enterococcus faecalis, Proteus
      mirabilis, Escherichia coli, Salmonella typhi, Klebsiella pneumonia and
      Pseudomonas aeruginosa. The antifungal potential was investigated by dilution
      method of Muller-Hinton agar media of the plants' samples. The fungal strains
      used were Aspergillis fumigatus, Aspergillis flavus and Aspergillis niger.
      Ceftriaxone and nystatin were used as standard drugs in antibacterial and
      antifungal assays respectively. RESULTS: Different fractions from N. thomsonianum
      were tested against five bacterial strains while the samples from A.
      consanguineum and E. caeruleum were tested against six bacterial strains. All the
      samples exhibited prominent antibacterial activity against the tested strains.
      Overall, chloroform and ethyl acetate fractions were found most potent among the
      three plants' samples. N. thomsonianum excelled among the three plants in
      antibacterial activity. Similarly, in antifungal assay, N. thomsonianum exhibited
      strong antifungal activity against the fungal strains. The chloroform fraction
      displayed MFCs of 175.67 +/- 5.20***, 29.33 +/- 5.48*** and 63.00 +/- 4.93***
      MUg/ml against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger
      respectively. The whole study demonstrates that all the three plant species were
      active against tested bacterial and fungal strains. CONCLUSION: It can be
      concluded from our findings that N. thomsonianum, A. consanguineum and E.
      caeruleum have broad antibacterial and antifungal potentials. In all of the
      plants' samples, chloroform and ethyl acetate fractions were more active.
      Furthermore, being the potent samples, the chloroform and ethyl acetate fractions
      of these plants can be subjected to column chromatography for the isolation of
      more effective antimicrobial drugs.

PMID- 27881121
TI  - Knowledge is not enough to solve the problems - The role of diagnostic knowledge
      in clinical reasoning activities.
AB  - BACKGROUND: Clinical reasoning is a key competence in medicine. There is a lack
      of knowledge, how non-experts like medical students solve clinical problems. It
      is known that they have difficulties applying conceptual knowledge to clinical
      cases, that they lack metacognitive awareness and that higher level cognitive
      actions correlate with diagnostic accuracy. However, the role of conceptual,
      strategic, conditional, and metacognitive knowledge for clinical reasoning is
      unknown. METHODS: Medical students (n = 21) were exposed to three different
      clinical cases and instructed to use the think-aloud method. The recorded
      sessions were transcribed and coded with regards to the four different categories
      of diagnostic knowledge (see above). The transcripts were coded using the
      frequencies and time-coding of the categories of knowledge. The relationship
      between the coded data and accuracy of diagnosis was investigated with
      inferential statistical methods. RESULTS: The use of metacognitive knowledge is
      correlated with application of conceptual, but not with conditional and strategic
      knowledge. Furthermore, conceptual and strategic knowledge application is
      associated with longer time on task. However, in contrast to cognitive action
      levels the use of different categories of diagnostic knowledge was not associated
      with better diagnostic accuracy. CONCLUSIONS: The longer case work and the more
      intense application of conceptual knowledge in individuals with high
      metacognitive activity may hint towards reduced premature closure as one of the
      major cognitive causes of errors in medicine. Additionally, for correct case
      solution the cognitive actions seem to be more important than the diagnostic
      knowledge categories.

PMID- 27881120
TI  - A scoping review of medical professionalism research published in the Chinese
      language.
AB  - BACKGROUND: The Chinese Medical Doctors Association (CMDA) adopted the Charter of
      Medical Professionalism in the New Millennium (Charter) and published the Chinese
      Medical Doctor Declaration (Declaration). This is an important step to re
      building medical professionalism in China at a time when the commercialization of
      health care has led to a decline in physician accountability and public trust in
      the profession. In response, authors have begun to examine and promote medical
      professionalism in China. This study aims to present the key research themes,
      identify research gaps and offer recommendations from reviewing the increasing
      pool of Chinese-language literature on medical professionalism. METHODS: A
      scoping review of Chinese language papers was conducted using the China National
      Knowledge Infrastructure (including China Academic Journals Full-text Database,
      China Doctoral Dissertations Full-text Database, Masters' Theses Full-text
      Database, China Core Newspapers Full-text Database, and China Yearbooks Full-text
      Database) (CNKI) database. RESULTS: Four major research themes were identified in
      Chinese discourse: (1) teaching professionalism, (2) practicing professionalism,
      (3) conceptualizing professionalism and (4) assessing professionalism. Overall,
      authors were concerned with the cultivation of humanism in physicians and
      emphasized the importance of communication skills to improve the physician
      patient relationship in China. They explored the role of traditional Chinese
      values, such as Confucian and Taoist values, as well as the Communist Party's
      political values, in promoting professional behaviour. CONCLUSIONS: Authors
      demonstrate increasing interest in medical professionalism in China. The
      literature is of variable quality and further empirical studies are required in
      order to evaluate teaching interventions and guide professionalism assessment. A
      common professionalism framework is absent and could be developed with
      consideration to China's socio-cultural context.

PMID- 27881122
TI  - Using WeChat official accounts to improve malaria health literacy among Chinese
      expatriates in Niger: an intervention study.
AB  - BACKGROUND: Malaria is the main health risk for Chinese expatriates working in
      Niger. Health education is a recommended intervention for prevention of malaria
      among non-immune travellers and expatriate workers. It is urgent to develop an
      effective and feasible way for these populations to obtain information about the
      prevention and treatment of malaria. METHODS: An individually randomized,
      unblinded, controlled trial was used to evaluate the effectiveness of using
      WeChat official accounts for health education to improve malaria health literacy
      among Chinese expatriates in Niger. A total 1441 participants completed a
      baseline malaria health literacy questionnaire and were randomly assigned to an
      intervention or comparison group in a ratio of 1:1. From July to October 2014, 50
      malaria prevention and treatment messages were sent to the intervention group; 50
      health news messages were concurrently sent to the control group. Both groups
      completed the malaria health literacy questionnaire again 4 months after the
      start of the education intervention. A questionnaire addressing satisfaction with
      the health education programme was completed by the intervention group. Malaria
      morbidity data for 2013 and 2014 were also collected. RESULTS: At baseline,
      participant health literacy rates were 58.29, 62, 54, and 34% for skills,
      knowledge, practice, and attitude, respectively. After the intervention, rates
      for all four aspects of malaria literacy were above 70%. There was greater change
      in knowledge, attitude, practice, skills, and overall health literacy among the
      intervention group compared with the controls, with a statistically significant
      difference (p < 0.01). This was especially true for acquisition of malaria
      related knowledge, practice and attitude; comprehensive intervention practices;
      and, correct use of rapid diagnostic tests (p < 0.001). The reported malaria
      morbidity during the study period decreased from 23.72 to 15.40%. Participants
      reported high levels of satisfaction with the WeChat health education programme
      with over 80% stating that they would continue to follow the programme.
      CONCLUSIONS: The present health education intervention, via a WeChat official
      account, for the prevention and treatment of malaria among non-immune travellers
      and expatriate workers proved to be an effective, sustainable, feasible, and well
      accepted strategy for improving malaria health literacy among Chinese expatriates
      in Niger.

PMID- 27881123
TI  - Reflective practice and its role in facilitating creative responses to dilemmas
      within clinical communication - a qualitative analysis.
AB  - BACKGROUND: Good communication is a major factor in delivering high quality in
      care. Research indicates that current communication skills training alone might
      not sufficiently enable students to find context-specific creative solutions to
      individual complex personal and interpersonal challenges in the clinical context.
      This study explores medical students' experiences with real communication
      dilemmas in a facilitated group setting. The aims were to gain a better
      understanding of whether and, if so, how reflective practice can enhance
      students' ability to find creative individual solutions in difficult
      communication situations and to identify factors within the reflective setting
      that foster their creative competency. METHODS: Thematic content analysis was
      used to perform a secondary analysis of semi-structured interview data from a
      qualitative evaluation of a group reflective practice training for final-year
      medical students. The categories that arose from the iterative deductive
      inductive approach were analyzed in light of current scientific understandings of
      creativity. RESULTS: Reflection on real difficult clinical communication
      situations appears to increase medical students' ability to handle such
      situations creatively. Although group reflection on clinical dilemmas involving
      personal aspects can stir up emotions, participating students stated they had
      learned a cognitive process tool that enhanced their communicative competence in
      clinical practice. They also described changes in personal attitudes: they felt
      more able to persevere and to tolerate ambiguity, described themselves more open
      and self-efficient in such complex clinical communication situations and thus
      more motivated. Furthermore, they reported on factors that were essential in this
      process, such as reflection on current and real challenges, a group format with a
      trainer. CONCLUSIONS: Reflective practice providing a cognitive process tool and
      using real clinical challenges and trainer support in communication education may
      provide learners with the skills and attitudes to develop creativity in practice.
      Implementing reflection training in clinical communication education may increase
      students' overall communicative competency.

PMID- 27881124
TI  - Effects of variable practice on the motor learning outcomes in manual wheelchair
      propulsion.
AB  - BACKGROUND: Handrim wheelchair propulsion is a cyclic skill that needs to be
      learned during rehabilitation. It has been suggested that more variability in
      propulsion technique benefits the motor learning process of wheelchair
      propulsion. The purpose of this study was to determine the influence of variable
      practice on the motor learning outcomes of wheelchair propulsion in able-bodied
      participants. Variable practice was introduced in the form of wheelchair
      basketball practice and wheelchair-skill practice. Motor learning was
      operationalized as improvements in mechanical efficiency and propulsion
      technique. METHODS: Eleven Participants in the variable practice group and 12
      participants in the control group performed an identical pre-test and a post
      test. Pre- and post-test were performed in a wheelchair on a motor-driven
      treadmill (1.11 m/s) at a relative power output of 0.23 W/kg. Energy consumption
      and the propulsion technique variables with their respective coefficient of
      variation were calculated. Between the pre- and the post-test the variable
      practice group received 7 practice sessions. During the practice sessions
      participants performed one-hour of variable practice, consisting of five
      wheelchair-skill tasks and a 30 min wheelchair basketball game. The control group
      did not receive any practice between the pre- and the post-test. RESULTS:
      Comparison of the pre- and the post-test showed that the variable practice group
      significantly improved the mechanical efficiency (4.5 +/- 0.6% -> 5.7 +/- 0.7%)
      in contrast to the control group (4.5 +/- 0.6% -> 4.4 +/- 0.5%) (group x time
      interaction effect p < 0.001).With regard to propulsion technique, both groups
      significantly reduced the push frequency and increased the contact angle of the
      hand with the handrim (within group, time effect). No significant group * time
      interaction effects were found for propulsion technique. With regard to
      propulsion variability, the variable practice group increased variability when
      compared to the control group (interaction effect p < 0.001). CONCLUSIONS:
      Compared to a control, variable practice, resulted in an increase in mechanical
      efficiency and increased variability. Interestingly, the large relative
      improvement in mechanical efficiency was concomitant with only moderate
      improvements in the propulsion technique, which were similar in the control
      group, suggesting that other factors besides propulsion technique contributed to
      the lower energy expenditure.

PMID- 27881125
TI  - Enhanced expression of the stemness-related factors OCT4, SOX15 and TWIST1 in
      ectopic endometrium of endometriosis patients.
AB  - BACKGROUND: Current evidence suggests that endometrial-derived stem cells,
      spilled in the peritoneal cavity via retrograde menstruation, are key players in
      the establishment of endometriotic lesions. The aim of this study was to
      determine the presence and distribution of the stemness-related factors OCT4,
      SOX15, TWIST1 and DCAMLK1 in women with and without endometriosis. METHODS:
      Immunohistochemical analysis was used to determine stromal and epithelial
      expression of OCT4, SOX15, TWIST1 and DCAMLK1 in endometriosis patient (EP)
      endometrium (n = 69) and endometriotic tissue (n = 90) and in control endometrium
      (n = 50). Quantitative Real-Time PCR of OCT4, SOX15 TWIST1 and DCAMLK1 was
      performed in paired samples of EP endometrium and endometriotic tissue. Co
      immunofluorescence staining was performed for OCT4 and SOX15. For statistical
      analyses we used unpaired t-test, Fisher combination test and Spearman test. For
      paired analyses, paired t-test and McNemar test were used. RESULTS: We detected a
      significant correlation between the expression of the established stem cell
      marker OCT4 and the stemness-related markers SOX15 (p < 0.001) and TWIST1 (p =
      0.002) but not DCAMLK1. We showed a colocalization of SOX15 and OCT4 in
      epithelial and stromal cells of endometriotic tissue by coimmunofluorescence. A
      concordant expression of OCT4 and SOX15 in the same sample was observed in
      epithelial cells of the endometriotic tissue (71.7%). The expression of stemness
      related factors was not associated with proliferative or secretory phase of the
      menstrual cycle in endometriosis patients but was found to be differentially
      expressed during the menstrual cycle in the control group. Increased expression
      of epithelial OCT4, SOX15 and TWIST1 was detected in endometriotic tissue
      compared to EP endometrium in paired (p = 0.021, p < 0.001 and p < 0.001) and
      unpaired analysis (p = 0.040, p < 0.001 and p = 0.001). CONCLUSION: Our findings
      support the hypothesis that upregulation of stem cell-related factors contribute
      to the establishment of endometriotic lesions. TRIAL REGISTRATION: The study was
      approved by the institutional review board (545/2010 on 6th of May 2014) of the
      Medical University of Vienna (
      http://ethikkommission.meduniwien.ac.at/fileadmin/ethik/media/dokumente/register/
      lle_2010.pdf ).

PMID- 27881126
TI  - Initial evaluation of prospective cardiac triggering using photoplethysmography
      signals recorded with a video camera compared to pulse oximetry and
      electrocardiography at 7T MRI.
AB  - BACKGROUND: Accurate synchronization between magnetic resonance imaging data
      acquisition and a subject's cardiac activity ("triggering") is essential for
      reducing image artifacts but conventional, contact-based methods for this task
      are limited by several factors, including preparation time, patient
      inconvenience, and susceptibility to signal degradation. The purpose of this work
      is to evaluate the performance of a new contact-free triggering method developed
      with the aim to eventually replace conventional methods in non-cardiac imaging
      applications. In this study, the method's performance is evaluated in the context
      of 7 Tesla non-enhanced angiography of the lower extremities. METHODS: Our main
      contribution is a basic algorithm capable of estimating in real-time the phase of
      the cardiac cycle from reflection photoplethysmography signals obtained from skin
      color variations of the forehead recorded with a video camera. Instead of finding
      the algorithm's parameters heuristically, they were optimized using videos of the
      forehead as well as electrocardiography and pulse oximetry signals that were
      recorded from eight healthy volunteers in and outside the scanner, with and
      without active radio frequency and gradient coils. Based on the video
      characteristics, synthetic signals were generated and the "best available" values
      of an objective function were determined using mathematical optimization. The
      performance of the proposed method with optimized algorithm parameters was
      evaluated by applying it to the recorded videos and comparing the computed
      triggers to those of contact-based methods. Additionally, the method was
      evaluated by using its triggers for acquiring images from a healthy volunteer and
      comparing the result to images obtained using pulse oximetry triggering. RESULTS:
      During evaluation of the videos recorded inside the bore with active radio
      frequency and gradient coils, the pulse oximeter triggers were labeled in 62.5%
      as "potentially usable" for cardiac triggering, the electrocardiography triggers
      in 12.5%, and the proposed method's triggers in 62.5%. Evaluation of the
      angiography images demonstrated that under appropriate conditions the method is
      feasible to produce an image quality comparable to pulse oximetry. CONCLUSION: We
      conclude that cardiac triggering using the proposed method is technically
      feasible. However, for improved reliability the signal-to-noise ratio of the
      videos will have to be addressed by either replacing the camera sensor, improving
      the illumination, or by use of additional signal filtering techniques.

PMID- 27881127
TI  - Patient-reported outcome measures in patients with peripheral arterial disease: a
      systematic review of psychometric properties.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is generally associated with
      considerable morbidity and reduced quality of life. Patient-reported outcome
      measures (PROMs) provide important information about the burden of disease and
      impact of treatment in affected patients. OBJECTIVES: The objective of the review
      was to identify and appraise studies reporting the psychometric evaluation of
      PROMs administered to a specified population of patients with PAD with a view to
      recommending suitable PROMs. METHODS: A systematic review of peer-reviewed
      English language articles was undertaken to identify primary studies reporting
      psychometric properties of PROMs in English-speaking patients with various stages
      of PAD. Comprehensive searches were completed up until January 2015. Study
      selection, data extraction and quality assessment were undertaken independently
      by at least two researchers. Findings were presented as tabular and narrative
      summaries based on accepted guidance. RESULTS: Psychometric evaluation of 6
      generic and 7 condition-specific PROMs reported in 14 studies contributed data to
      the review. The frequently reported measure was the SF-36 (n = 11 studies);
      others included the Walking Impairment Questionnaire (n = 8 studies), EQ-5D (n =
      5 studies) and the Vascular Quality of Life Questionnaire (n = 3 studies).
      Studies included a diverse PAD population and varied in methodology, including
      approach to validation of PROMs. CONCLUSIONS: Various PROMs have been validated
      in patients with PAD but no study provided evidence of a full psychometric
      evaluation in the patient population. Careful selection is required to identify
      reliable and valid PROMs to use in clinical and research settings.

PMID- 27881128
TI  - Effect of intensive insulin treatment on plasma levels of lipoprotein-associated
      phospholipase A2 and secretory phospholipase A2 in patients with newly diagnosed
      type 2 diabetes.
AB  - BACKGROUND: China has the highest absolute disease burden of diabetes worldwide.
      For diabetic patients, diabetes-related vascular complications are major causes
      of morbidity and mortality. The roles of lipoprotein-associated phospholipase A2
      (Lp-PLA2) and secretory phospholipase A2 (sPLA2) as inflammatory markers have
      been recently evaluated in the pathogenesis of both diabetes and atherosclerosis.
      We aimed to determine the mechanism through which patients with newly diagnosed
      type 2 diabetes gain long-term vascular benefit from intensive insulin therapy by
      evaluating the change in Lp-PLA2 and sPLA2 levels after early intensive insulin
      treatment and its relevance with insulin resistance and pancreatic beta-cell
      function. METHODS: In total, 90 patients with newly diagnosed type 2 diabetes
      mellitus were enrolled. All patients received continuous subcutaneous insulin
      infusion (CSII) for approximately 2 weeks. Intravenous glucose-tolerance test
      (IVGTT) and oral glucose-tolerance test (OGTT) were performed, and plasma
      concentrations of Lp-PLA2 and sPLA2 were measured before and after CSII. RESULTS:
      Levels of Lp-PLA2 and sPLA2 were significantly higher in diabetic patients with
      macroangiopathy than in those without (P < 0.05). After CSII, the sPLA2 level
      decreased significantly in all diabetic patients (P < 0.05), while the Lp-PLA2
      level changed only in those with macroangiopathy (P < 0.05). The area under the
      curve of insulin in IVGTT and OGTT, the acute insulin response (AIR3-5), early
      phase of insulin secretion (DeltaIns30/DeltaG30), modified beta-cell function
      index, and homeostatic model assessment for beta-cell function (HOMA-beta)
      increased after treatment even when adjusted for the influence of insulin
      resistance (IR; P < 0.001). The HOMA-IR was lower after treatment, and the three
      other indicators adopted to estimate insulin sensitivity (ISIced, IAI, and
      QUICKI) were higher after treatment (P < 0.05). Correlation analysis showed that
      the decrease in the Lp-PLA2 and sPLA2 levels was positively correlated with a
      reduction in HOMA-IR after CSII (P < 0.05). Additionally, multiple linear
      regression analysis showed that Lp-PLA2 and sPLA2 independently correlated with
      HOMA-IR (P < 0.05). CONCLUSIONS: Lp-PLA2 and sPLA2 are closely related to insulin
      resistance and macroangiopathy in diabetic patients. Intensive insulin therapy
      might help improve IR and protect against diabetic macroangiopathy by influencing
      the Lp-PLA2 and sPLA2 levels. TRIAL REGISTRATION: ChiCTR-TRC-10001618 2010
      September 16.

PMID- 27881130
TI  - Electronic reminders to facilitate longitudinal care: a mixed-methods study in
      general practices.
AB  - BACKGROUND: Longitudinal, patient-centered care represents a challenge for
      general practitioners (GPs), and in this context, reminder systems can offer
      targeted support. This study aimed to identify details of such reminders: (1)
      contents of care addressed, (2) their mode of display in the electronic health
      record (EHR), (3) their visual appearance, (4) personnel responsibilities for
      editing and applying reminders, and (5) use of reminders for patient recall.
      METHODS: This mixed-methods study comprised (1) a cross-sectional survey among
      185 GP practices from a German university network, and (2) structured
      observations of reminder utilization in six practices based on a clinical
      vignette describing a multimorbid senior with 26 care needs. Descriptive
      statistics were performed for survey data. The practice observations were
      analyzed by portraying different types of reminders. RESULTS: Seventy-three of
      185 practices completed the survey (39.5%): 98.6% reported using reminders in the
      EHR. Frequent care contents addressed were allergies/adverse drug events (95.8%),
      preventive measures (93.1%), participation in disease management programs
      (87.5%), chronic diseases (75.0%), and upcoming vaccinations (68.1%). Practice
      observations showed a variety of mainly self-configured reminders. In a patients'
      EHR, information was displayed (1) compiled in a separate field, (2) scattered
      throughout the EHR, and/or (3) in a pop-up window. The visual appearance of
      electronic reminders varied: (1) colored fields with short text, (2) EHR entries
      and/or billing codes in pre-defined colors, (3) abbreviations within the
      treatment documentation, (4) symbols within the treatment documentation, (5)
      symbols linked to free text fields, and (6) traffic light schemes. Five practices
      self-designed reminders 'as needed'; one practice applied an EHR-embedded, pre
      defined reminder system. Practices used reminders for a mean of 13.3 of the 26
      aspects of care detailed in the clinical vignette (range: 9-21; standard
      deviation (SD): 4.3). Practices needed 20-35 min (mean: 27.5; SD: 6.1) to
      retrieve the information requested. CONCLUSIONS: Most GP practices use self
      designed, visual reminders for some aspects of care, yet data-based,
      sophisticated solutions are needed to improve longitudinal care. TRIAL
      REGISTRATION: German Clinical Trials Register, unique identifying number:
      DRKS00008777 (date of registration: 06/19/2015).

PMID- 27881129
TI  - Impact of dipeptidyl peptidase-4 inhibitors on serum adiponectin: a meta
      analysis.
AB  - BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated
      with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other
      cardiovascular risk factors such as insulin resistance. Therefore, low levels of
      adiponectin are associated with a higher risk for diabetes and cardiovascular
      disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the
      treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through
      interacting with DPP4 substrate and increase serum incretins such as glucagon
      like peptide-1 (GLP-1). The present study aimed to evaluate the effect of DPP4i
      on serum adiponectin in T2DM patients. METHODS: The PubMed, Embase, and Cochrane
      library databases were searched from inception to February 2016. Randomized
      controlled trials, evaluating the DPP4i (sitagliptin and vildagliptin) versus
      comparator (placebo or active-comparison), in T2DM patients with duration of >=
      12 weeks, were identified. Weighted differences in means of adiponectin levels
      were calculated by using a fixed or random-effects model. RESULTS: Ten randomized
      controlled trials, including 1,495 subjects, were identified. Compared with
      placebo, DPP4i (sitagliptin and vildagliptin) treatment significantly elevated
      adiponectin levels by 0.74 MUg/mL (95% confidence interval [CI], 0.45 to 1.03)
      relative to that using an active-comparison by 0.00 MUg/mL (95% CI, -0.57 to
      0.56). Compared with active-comparison, vildagliptin treatment increased
      adiponectin levels by 0.32 MUg/mL (95% CI, -0.01 to 0.65), whereas sitagliptin
      treatment decreased adiponectin levels by -0.24 MUg/mL (95% CI, -1.07 to 0.58).
      Trials examining effects of other DPP4i were not found. CONCLUSIONS: Sitagliptin
      and vildagliptin increased serum adiponectin levels and had no stronger effect
      than traditional oral antidiabetic drugs. Further trials with larger sample size
      are needed to confirm the results and investigate the association between serum
      adiponectin levels and treatment of other DPP-4 inhibitors. TRIAL REGISTRATION:
      Registration No in PROSPERO: CRD42016037399 .

PMID- 27881131
TI  - An evaluation of equity and equality in physical activity policies in four
      European countries.
AB  - BACKGROUND: There is strong research evidence on the importance of health equity
      and equality for wellbeing in societies. As chronic non-communicable diseases are
      widespread, the positive impact of physical activity (PA) on health has gained
      importance. However, PA at the population level is far from optimal. PA depends
      not only on individual factors, but also on policies for PA in sport, health,
      transport, education and other sectors, on social and cultural factors, and on
      the environment. Addressing health inequalities and inequities in PA promotion
      policies could benefit from policy development processes based on partnership and
      collaboration between various sectors, researchers, practitioners and policy
      makers (= cross-sectoral, evidence-informed policy making). The objective of this
      article is to describe how equity and equality was addressed in PA policies in
      four EU member states (Denmark, Finland, Romania and England), who were partners
      in the REPOPA project ( www.repopa.eu , EC/FP7/Health Research/GA 281532).
      METHODS: Content analysis of 14 PA policies and 61 interviews were undertaken
      between 2012 and 2013 with stakeholders involved in developing PA policies in
      partner countries. RESULTS: Even though specific population subgroups were
      mentioned in the policy documents analysed, they were not necessarily defined as
      vulnerable populations nor was there a mention of additional emphasis to support
      such groups from being marginalised by the policy due to inequity or inequality.
      There were no clear objectives and activities in the analysed policies suggesting
      commitment of additional resources in favour of such groups. Addressing equity
      and equality were often not included in the core aims of the policies analysed;
      these aspects were mentioned in the background of the policy documents analysed,
      without being explicitly stated in the aims or activities of the policies. In
      order to tackle health inequities and inequalities and their consequences on the
      health status of different population subgroups, a more instrumental approach to
      health equality and equity in PA promotion policies is needed. Policies should
      include aims to address health inequalities and inequities as fundamental
      objectives and also consider opportunities to allocate resources to reduce them
      for identified groups in this regard: the socially excluded, the remote, and the
      poor. CONCLUSIONS: The inclusion of aspects related to health inequalities and
      inequities in PA policies needs monitoring, evaluation and transparent
      accountability if we are to see the best gains in health of socially
      disadvantaged group. To tackle health inequities and inequalities governance
      structures need to take into consideration proportionate universalism. Thus, to
      achieve change in the social determinants of health, policy makers should pay
      attention to PA and proportionally invest for universal access to PA services. PA
      promotion advocates should develop a deeper awareness of political and policy
      structures and require more equity and equality in PA policies from those who
      they seek to influence, within specific settings for policy making and developing
      the policy agenda.

PMID- 27881132
TI  - Integrated safety and efficacy analysis of once-daily fluticasone furoate for the
      treatment of asthma.
AB  - BACKGROUND: Fluticasone furoate is a once-daily inhaled corticosteroid. This
      report provides an overview of safety and efficacy data that support the use of
      once-daily fluticasone furoate 100 MUg or 200 MUg in adult and adolescent asthma
      patients. METHODS: Fourteen clinical studies (six Phase II and eight Phase III)
      were conducted as part of the fluticasone furoate global clinical development
      programme in asthma. Safety data from 10 parallel-group, randomised, double-blind
      Phase II and III studies (including 3345 patients who received at least one dose
      of fluticasone furoate) were integrated to provide information on adverse events,
      withdrawals, laboratory assessments, vital signs and hypothalamic-pituitary
      adrenal axis function. The efficacy of once-daily fluticasone furoate was
      evaluated in all included studies. RESULTS: Once-daily fluticasone furoate 100
      MUg and 200 MUg safety profiles were consistent with those reported for other
      inhaled corticosteroids, and both doses consistently demonstrated efficacy versus
      placebo. In the integrated analysis, no dose-response relationship was observed
      for the overall incidence of adverse events and there were no significant effects
      of fluticasone furoate on hypothalamic-pituitary-adrenal axis function.
      CONCLUSION: Once-daily fluticasone furoate 100 MUg and 200 MUg had acceptable
      safety profiles and was efficacious in adult and adolescent patients with asthma.
      There was no evidence of cortisol suppression at studied doses. TRIAL
      REGISTRATIONS: GSK (NCT01499446/FFA20001, NCT00398645/FFA106783,
      NCT00766090/112202, NCT00603746/FFA109684, NCT00603278/FFA109685,
      NCT00603382/FFA109687, NCT01436071/115283, NCT01436110/115285,
      NCT01159912/112059, NCT01431950/114496, NCT01165138/HZA106827,
      NCT01086384/106837, NCT01134042/HZA106829 and NCT01244984/1139879).

PMID- 27881133
TI  - Alcohol and stroke: the splitters win again.
AB  - Study of the relationships of alcohol drinking and risk of stroke can readily
      become mired in the labyrinthine interactions of drinking categorizations, non
      linear associations, disparate cardiovascular conditions, and the heterogeneous
      types of stroke. This Commentary discusses the recent article by Larsson et al.
      (BMC Medicine 14:178, 2016). The authors split their material into separate meta
      analyses of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic
      stroke, finding disparate alcohol-stroke relationships. Our Commentary pursues
      the disparity theme, using the lumpers versus splitters paradigm to explore
      several aspects of this complex area.Please see related article:
      http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0721-4 .

PMID- 27881134
TI  - Low dose radiation risks for women surviving the a-bombs in Japan: generalized
      additive model.
AB  - BACKGROUND: Analyses of cancer mortality and incidence in Japanese A-bomb
      survivors have been used to estimate radiation risks, which are generally higher
      for women. Relative Risk (RR) is usually modelled as a linear function of dose.
      Extrapolation from data including high doses predicts small risks at low doses.
      Generalized Additive Models (GAMs) are flexible methods for modelling non-linear
      behaviour. METHODS: GAMs are applied to cancer incidence in female low dose
      subcohorts, using anonymous public data for the 1958 - 1998 Life Span Study, to
      test for linearity, explore interactions, adjust for the skewed dose
      distribution, examine significance below 100 mGy, and estimate risks at 10 mGy.
      RESULTS: For all solid cancer incidence, RR estimated from 0 - 100 mGy and 0 - 20
      mGy subcohorts is significantly raised. The response tapers above 150 mGy. At low
      doses, RR increases with age-at-exposure and decreases with time-since-exposure,
      the preferred covariate. Using the empirical cumulative distribution of dose
      improves model fit, and capacity to detect non-linear responses. RR is elevated
      over wide ranges of covariate values. Results are stable under simulation, or
      when removing exceptional data cells, or adjusting neutron RBE. Estimates of
      Excess RR at 10 mGy using the cumulative dose distribution are 10 - 45 times
      higher than extrapolations from a linear model fitted to the full cohort. Below
      100 mGy, quasipoisson models find significant effects for all solid, squamous,
      uterus, corpus, and thyroid cancers, and for respiratory cancers when age-at
      exposure > 35 yrs. Results for the thyroid are compatible with studies of
      children treated for tinea capitis, and Chernobyl survivors. Results for the
      uterus are compatible with studies of UK nuclear workers and the Techa River
      cohort. CONCLUSION: Non-linear models find large, significant cancer risks for
      Japanese women exposed to low dose radiation from the atomic bombings. The risks
      should be reflected in protection standards.

PMID- 27881135
TI  - Cat's whiskers (Orthosiphon stamineus) tea modulates arthritis pathogenesis via
      the angiogenesis and inflammatory cascade.
AB  - BACKGROUND: Orthosiphon stamineus is used traditionally to treat gout, arthritis,
      and inflammatory related conditions. The in vitro anti-inflammatory effects of
      the plant have been scientifically investigated. The goal of the present study
      was to evaluate the potential of the 50% ethanol extract of O. stamineus (EOS) to
      treat rheumatoid arthritis. METHODS: Anti-arthritic activity was assessed using
      the in vitro heat denaturation test and the (FCA)-induced arthritis model.
      Efficacy was assessed by measurements of paw edema and granulation, X-ray
      radiography, fluorescence molecular tomography (FMT), and histological
      evaluation. Levels of (TNF-alpha), interleukin-1 (IL-1), and (COX-1 and COX-2)
      were analyzed in vitro in lipopolysaccharide (LPS)-stimulated human macrophage
      (U937). TNF-alpha and IL-1 levels in the serum samples of arthritic rats were
      also measured using an ELISA kit. RESULTS: Treatment with EOS resulted in dose
      dependent inhibition of paw edema in acute and chronic models of inflammation. It
      also inhibited significantly the production of TNF-alpha, IL-1 COX-1, and COX-2
      in the LPS-stimulated U937 macrophages. EOS significantly suppressed FCA-induced
      paw edema as well as the serum levels of TNF-alpha and IL-1. X-rays of the
      synovial joint of the hind leg showed considerable improvement in joint integrity
      and recovery of tibia-talus bones from degeneration and osteoporotic lesions.
      Histology of proximal interphalangeal joints of EOS-treated animals showed
      obvious protection of cartilage and soft tissue. Finally, FMT analysis strongly
      supported the anti-arthritic effect of EOS. EOS had high phenolic and total
      flavonoid content as well as strong antioxidant activity. CONCLUSIONS: Results
      illustrated that the anti-arthritic properties of O. stamineus could be
      beneficial for prevention and management of rheumatoid arthritis and other
      chronic inflammatory disorders. Illustration of the Anti- arthritis efficacy of
      Orthosiphon Stamineus standardized extract.

PMID- 27881136
TI  - Community health workers adherence to referral guidelines: evidence from studies
      introducing RDTs in two malaria transmission settings in Uganda.
AB  - BACKGROUND: Many malaria-endemic countries have implemented national community
      health worker (CHW) programmes to serve remote populations that have poor access
      to malaria diagnosis and treatment. Despite mounting evidence of CHWs' ability to
      adhere to malaria rapid diagnostic tests (RDTs) and treatment guidelines, there
      is limited evidence whether CHWs adhere to the referral guidelines and refer
      severely ill children for further management. In southwest Uganda, this study
      examined whether CHWs referred children according to training guidelines and
      described factors associated with adherence to the referral guideline. METHODS: A
      secondary analysis was undertaken of data collected during two cluster-randomized
      trials conducted between January 2010 and July 2011, one in a moderate-to-high
      malaria transmission setting and the other in a low malaria transmission setting.
      All CHWs were trained to prescribe artemisinin-based combination therapy (ACT)
      and recognize symptoms in children that required immediate referral to the
      nearest health centre. Intervention arm CHWs had additional training on how to
      conduct an RDT; CHWs in the control arm used a presumptive diagnosis for malaria
      using clinical signs and symptoms. CHW treatment registers were reviewed to
      identify children eligible for referral according to training guidelines
      (temperature of >=38.5  degrees C), to assess whether CHWs adhered to the
      guidelines and referred them. Factors associated with adherence were examined
      with logistic regression models. RESULTS: CHWs failed to refer 58.8% of children
      eligible in the moderate-to-high transmission and 31.2% of children in the low
      transmission setting. CHWs using RDTs adhered to the referral guidelines more
      frequently than CHWs not using RDTs (moderate-to-high transmission: 50.1 vs
      18.0%, p = 0.003; low transmission: 88.5 vs 44.1%, p < 0.001). In both settings,
      fewer than 20% of eligible children received pre-referral treatment with rectal
      artesunate. Children who were prescribed ACT were very unlikely to be referred in
      both settings (97.7 and 73.3% were not referred in the moderate-to-high and low
      transmission settings, respectively). In the moderate-to-high transmission
      setting, day and season of visit were also associated with the likelihood of
      adherence to the referral guidelines, but not in the low transmission setting.
      CONCLUSIONS: CHW adherence to referral guidelines was poor in both transmission
      settings. However, training CHWs to use RDT improved correct referral of children
      with a high fever compared to a presumptive diagnosis using sign and symptoms. As
      many countries scale up CHW programmes, routine monitoring of reported data
      should be examined carefully to assess whether CHWs adhere to referral guidelines
      and take remedial actions where required.

PMID- 27881138
TI  - BoHV-4-based vector delivering Ebola virus surface glycoprotein.
AB  - BACKGROUND: Ebola virus (EBOV) is a Category A pathogen that is a member of
      Filoviridae family that causes hemorrhagic fever in humans and non-human
      primates. Unpredictable and devastating outbreaks of disease have recently
      occurred in Africa and current immunoprophylaxis and therapies are limited. The
      main limitation of working with pathogens like EBOV is the need for costly
      containment. To potentiate further and wider opportunity for EBOV prophylactics
      and therapies development, innovative approaches are necessary. METHODS: In the
      present study, an antigen delivery platform based on a recombinant bovine
      herpesvirus 4 (BoHV-4), delivering a synthetic EBOV glycoprotein (GP) gene
      sequence, BoHV-4-syEBOVgD106DeltaTK, was generated. RESULTS: EBOV GP was
      abundantly expressed by BoHV-4-syEBOVgD106DeltaTK transduced cells without
      decreasing viral replication. BoHV-4-syEBOVgD106DeltaTK immunized goats produced
      high titers of anti-EBOV GP antibodies and conferred a long lasting (up to 6
      months), detectable antibody response. Furthermore, no evidence of BoHV-4
      syEBOVgD106DeltaTK viremia and secondary localization was detected in any of the
      immunized animals. CONCLUSIONS: The BoHV-4-based vector approach described here,
      represents: an alternative antigen delivery system for vaccination and a proof of
      principle study for anti-EBOV antibodies generation in goats for potential
      immunotherapy applications.

PMID- 27881139
TI  - Next of kin's experiences of involvement during involuntary hospitalisation and
      coercion.
AB  - BACKGROUND: Norway has extensive and detailed legal requirements and guidelines
      concerning involvement of next of kin (NOK) during involuntary hospital treatment
      of seriously mentally ill patients. However, we have little knowledge about what
      happens in practice. This study explores NOK's views and experiences of
      involvement during involuntary hospitalisation in Norway. METHODS: We performed
      qualitative interviews-focus groups and individual-with 36 adult NOK to adults
      and adolescents who had been involuntarily admitted once or several times. The
      semi-structured interview guide included questions on experiences with and views
      on involvement during serious mental illness and coercion. RESULTS: Most of the
      NOK were heavily involved in the patient's life and illness. Their conceptions of
      involvement during mental illness and coercion, included many important aspects
      adding to the traditional focus on substitute decision-making. The overall
      impression was, with a few exceptions, that the NOK had experienced lack of
      involvement or had negative experiences as NOK in their encounters with the
      health services. Not being seen and acknowledged as important caregivers and co
      sufferers were experienced as offensive and could add to their feelings of guilt.
      Lack of involvement had as a consequence that vital patient information which the
      NOK possessed was not shared with the patient's therapists. CONCLUSIONS: Despite
      public initiatives to improve the involvement of NOK, the NOK in our study felt
      neglected, unappreciated and dismissed. The paper discusses possible reasons for
      the gap between public policies and practice which deserve more attention: 1. A
      strong and not always correct focus on legal matters. 2. Little emphasis on the
      role of NOK in professional ethics. 3. The organisation of health services and
      resource constraints. 4. A conservative culture regarding the role of next of kin
      in mental health care. Acknowledging these reasons may be helpful to understand
      deficient involvement of the NOK in voluntary mental health services.

PMID- 27881140
TI  - Early signs of multi-walled carbon nanotbues degradation in macrophages, via an
      intracellular pH-dependent biological mechanism; importance of length and
      functionalization.
AB  - BACKGROUND: Carbon nanotubes (CNT) can interact with the biological environment,
      which could participate in their associated toxicity. We recently demonstrated
      that pH is an important player of CNT fate inside macrophages. We wanted to
      further characterize such process, and therefore designed a study dedicated to
      decipher CNT biodegradation by macrophages, as a function of two major physico
      chemical properties in regard with nanotoxicology; length and degree of
      functionalization. To achieve our aim, we synthesized, following a single initial
      production process, four MWCNT differing in length and/or surface chemistry: S
      CNT (short), SF-CNT (short functionalized), L-CNT (long) and LF-CNT (long
      functionalized). RESULTS: Raman spectroscopy analysis performed on CNT recovered
      after exposure of RAW 264.7 macrophages for 6, 24, or 48 h demonstrate that CNT
      show early signs of biodegradation over time inside macrophages. The modulation
      of CNT length and functionalization, resulting in the modification of iron
      accessibility, both represent critical determinants of the biodegradation
      process; short pristine CNT were more prone to biodegradation than long CNT
      (pristine or functionalized), while short functionalized CNT were protected.
      Incubation of cells with Concanamycin completely prevents CNT from being
      modified, demonstrating that this biodegradation process is dependent on an
      intracellular pH-dependent mechanism. Interestingly, and despite evidence of
      degradation via Raman spectroscopy, the CNT length and diameter were not altered
      during the course of the study. CONCLUSIONS: In conclusion, our results identify
      a new mechanism of CNT biodegradation inside macrophages. This could give new
      insights for the understanding of CNT-associated toxicity, and represent
      important tools to develop safe(r)-by-design nanomaterials.

PMID- 27881137
TI  - Balancing the immune response in the brain: IL-10 and its regulation.
AB  - BACKGROUND: The inflammatory response is critical to fight insults, such as
      pathogen invasion or tissue damage, but if not resolved often becomes detrimental
      to the host. A growing body of evidence places non-resolved inflammation at the
      core of various pathologies, from cancer to neurodegenerative diseases. It is
      therefore not surprising that the immune system has evolved several regulatory
      mechanisms to achieve maximum protection in the absence of pathology. MAIN BODY:
      The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of
      the most important mechanisms evolved by many immune cells to counteract damage
      driven by excessive inflammation. Innate immune cells of the central nervous
      system, notably microglia, are no exception and produce IL-10 downstream of
      pattern recognition receptors activation. However, whereas the molecular
      mechanisms regulating IL-10 expression by innate and acquired immune cells of the
      periphery have been extensively addressed, our knowledge on the modulation of IL
      10 expression by central nervous cells is much scattered. This review addresses
      the current understanding on the molecular mechanisms regulating IL-10 expression
      by innate immune cells of the brain and the implications of IL-10 modulation in
      neurodegenerative disorders. CONCLUSION: The regulation of IL-10 production by
      central nervous cells remains a challenging field. Answering the many remaining
      outstanding questions will contribute to the design of targeted approaches aiming
      at controlling deleterious inflammation in the brain.

PMID- 27881142
TI  - Ethnoagroforestry: integration of biocultural diversity for food sovereignty in
      Mexico.
AB  - BACKGROUND: Documenting the spectrum of ecosystem management, the roles of
      forestry and agricultural biodiversity, TEK, and human culture for food
      sovereignty, are all priority challenges for contemporary science and society.
      Ethnoagroforestry is a research approach that provides a theoretical framework
      integrating socio-ecological disciplines and TEK. We analyze in this study
      general types of Agroforestry Systems of Mexico, in which peasants, small
      agriculturalist, and indigenous people are the main drivers of AFS and planning
      of landscape diversity use. We analyzed the actual and potential contribution of
      ethnoagroforestry for maintaining diversity of wild and domesticated plants and
      animals, ecosystems, and landscapes, hypothesizing that ethnoagroforestry
      management forms may be the basis for food sufficiency and sovereignty in Mexican
      communities, regions and the whole nation. METHODS: We conducted research and
      systematization of information on Mexican AFS, traditional agriculture, and
      topics related to food sovereignty from August 2011 to May 2015. We constructed
      the database Ethnoagroforestry based on information from our own studies, other
      databases, Mexican and international specialized journals in agroforestry and
      ethnoecology, catalogues and libraries of universities and research centers,
      online information, and unpublished theses. We analyzed through descriptive
      statistical approaches information on agroforestry systems of Mexico including
      148 reports on use of plants and 44 reports on use of animals. RESULTS: Maize,
      beans, squashes and chili peppers are staple Mesoamerican food and principal
      crops in ethnoagroforestry systems practiced by 21 cultural groups throughout
      Mexico (19 indigenous people) We recorded on average 121 +/- 108 (SD) wild and
      domesticated plant species, 55 +/- 27% (SD) of them being native species; 44 +/-
      23% of the plant species recorded provide food, some of them having also
      medicinal, firewood and fodder uses. A total of 684 animal species has been
      recorded (17 domestic and 667 wild species), mainly used as food (34%).
      CONCLUSIONS: Ethnoagroforestry an emergent research approach aspiring to
      establish bases for integrate forestry and agricultural diversity, soil, water,
      and cultural richness. Its main premise is that ethnoagroforestry may provide the
      bases for food sovereignty and sustainable ecosystem management.

PMID- 27881141
TI  - Analysis of epithelial-mesenchymal transition markers in the histogenesis of
      hepatic progenitor cell in HBV-related liver diseases.
AB  - BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs)
      remain unclear. This study aimed to investigate the involvement of epithelial
      mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver
      specimens from patients with HBV-related hepatitis and cirrhosis were
      investigated with double immunofluorescence labeling to detect antigens
      associated with HPCs and EMT. Ductular reactions were subjected to quantitative
      reverse transcription PCR following isolation by laser capture microdissection.
      Electron microscopic examination was performed to find an ultrastructural
      evidence of EMT. RESULTS: The number of EpCAM-positive HPCs was proportional to
      the disease severity. The S100A4 expression of HPCs was firstly observed in mild
      hepatitis and increased significantly in moderate hepatitis, but decreased in
      severe hepatitis and cirrhosis. The levels of MMP-2, Twist, and Snail increased
      in direct proportion to the number of HPCs. Some hepatocytes adjacent to portal
      tracts in cirrhosis showed positivity for MMP-2. Although CK7 and E-cadherin
      levels decreased in mild and moderate hepatitis, HPCs re-expressed both of them
      in severe hepatitis and cirrhosis. However, HPCs expressed neither vimentin nor
      alphaSMA. The relative mRNA expression levels of EpCAM and EMT-associated markers
      supported immunohistochemical results. Electron microscopic examination
      demonstrated the existence of intercellular junctions among HPCs, cholangiocytes,
      and intermediate hepatocyte-like cells. CONCLUSION: We provided preliminary
      evidence for the involvement of EMT in the histogenesis of HPCs from
      cholangiocytes in HBV-related liver diseases. HPCs may re-transdifferentiate into
      hepatocytes, and the differentiation direction depends, at least in part, on
      interactions between HPCs and the surrounding microenvironment, especially the
      non-resolving inflammation caused by HBV infection.

PMID- 27881143
TI  - Weekly versus every-three-weeks platinum-based chemoradiation regimens for head
      and neck cancer.
AB  - BACKGROUND: The majority of chemoradiation (CRT) trials for locally advanced head
      and neck squamous cell carcinoma (HNSCC) have relied on platinum-based
      chemotherapy regimens administered every-3-weeks. However, given the increased
      utilization of weekly platinum regimens, it remains unclear how different
      chemotherapy schedules compare regarding efficacy and toxicity. METHODS: We
      retrospectively identified 212 patients with HNSCC who were treated at a single
      academic medical center with concurrent platinum-based CRT given weekly (N = 68)
      or every-three-weeks (N = 144). JMP version 10 (SAS Institute) was used for
      statistical analysis. Discrete variables were compared with the chi-square test
      and differences in the medians were assessed using the Wilcoxon test. Survival
      curves were constructed using the Kaplan-Meier method and significance was
      assessed using the log rank test. For univariate analysis and multivariate
      analysis, we used Cox proportional hazard or logistic regression models to
      compare differences in survival or differences in categorical variables,
      respectively. RESULTS: Patients receiving weekly platinum regimens were more
      likely to be older (median age 61.4 vs. 55.5 y; P < .001), have high or very high
      Charlson comorbidity index (45.6% vs. 27.8%; P = .01), and receive carboplatin
      based chemotherapy (6.3% vs. 76.5%; P < .001). Weekly and every-3-week platinum
      regimens had similar locoregional control (HR 1.10; 95% CI 0.63-1.88; P = .72),
      progression-free survival (HR 1.13; 95% CI 0.75-1.69; P = .55), and overall
      survival (HR 1.11; 95% CI 0.64-1.86; P = .71). Every-3-weeks platinum regimens
      were associated with increased days of hospitalization (median: 3 days vs. 0
      days; P = .03) and acute kidney injury (AKI) during radiotherapy (50.0% vs.
      22.1%; P < .001). On multivariate analysis, AKI was significantly associated with
      every-3-weeks regimens (OR: 24.38; 95% CI 3.00-198.03; P = .003) and high
      comorbidity scores (OR: 2.74; 95% CI 2.15-5.99; P = .01). CONCLUSIONS: Our
      results suggest that every-3-weeks and weekly platinum-containing CRT regimens
      have similar disease control but weekly platinum regimens are associated with
      less acute toxicity.

PMID- 27881144
TI  - Comparison of treatment response, remission rate and drug adherence in
      polyarticular juvenile idiopathic arthritis patients treated with etanercept,
      adalimumab or tocilizumab.
AB  - BACKGROUND: Treatment response, remission rates and compliance in patients with
      polyarticular juvenile idiopathic arthritis (polyJIA) treated with adalimumab,
      etanercept, or tocilizumab were analyzed in clinical practice. METHODS: Data
      collected in the German BIKER registry were analyzed in patients with polyJIA who
      started treatment with approved biologics, adalimumab, etanercept or tocilizumab,
      from 2011 to 2015. Baseline patient characteristics, treatment response, safety
      and drug survival were compared. RESULTS: Two hundred thirty-six patient started
      adalimumab, 419 etanercept and 74 tocilizumab, with differences in baseline
      patient characteristics. Baseline Juvenile Disease Activity Score (JADAS)10 (mean
      +/- SD) in the adalimumab/etanercept/tocilizumab cohorts was 12.1+/-7.6, 13.8 +/-
      7.1 and 15.1 +/- 7.4, respectively (adalimumab vs etanercept, p = 0.01), and
      Childhood Health Assessment Questionnaire (CHAQ)-disability index scores was 0.43
      +/- 0.58, 0.59 +/- 0.6 and 0.63 +/- 0.55, respectively (adalimumab vs etanercept,
      p < 0.001). Uveitis history was more frequent in the adalimumab cohort (OR 5.73;
      p < 0.001). Balanced patients' samples were obtained by a generalized propensity
      score to adjust for baseline differences. Pediatric ACR30/50/70/90 criterion
      improvement after 3 months treatment was achieved by 68%/60%/42%/24% in the
      etanercept cohort, 67%/59%/43%/27% in the adalimumab cohort and 61%/52%/35%/26%
      in the tocilizumab cohort. At 24 months, JADAS minimal disease activity was
      achieved in 52.4%/61.3%/52.4% and JADAS remission in 27.9%/34.8%/27.9% patients
      in the adalimumab/etanercept/tocilizumab cohorts, respectively. Etanercept was
      used in 95.5% of patients as a first biologic, adalimumab in 50.8% and
      tocilizumab in 20.2%. There were no important differences in efficacy between
      first-line and second-line use of biologics. In total 60.4%/49.4%/31.1% patients
      discontinued adalimumab/etanercept/tocilizumab, respectively (HR for adalimumab
      1.67; p < 0.001; HR for tocilizumab 0.35; p = 0.001). Drug survival rates did not
      differ significantly in patients on biologic monotherapy compared with
      combination therapy with methotrexate. Over 4 years observation under
      etanercept/adalimumab/tocilizumab, 996/386/103 adverse events, and 148/119/26
      serious adverse events, respectively, were reported. CONCLUSIONS: In clinical
      practice, etanercept is most frequently used as first-line biologic.
      Adalimumab/etanercept/tocilizumab showed comparable efficacy toward polyJIA.
      Overall, tolerance was acceptable. Interestingly, compliance was highest with
      tocilizumab and lowest with adalimumab. This study provides the first indication
      for the comparison of different biologic agents in polyarticular JIA based on
      observational study data with all their weaknesses and demonstrates the need for
      well-controlled head-to-head studies for confirmation.

PMID- 27881146
TI  - Evaluation of a large healthy lifestyle program: informing program implementation
      and scale-up in the prevention of obesity.
AB  - BACKGROUND: The Healthy Lifestyle Program for women (HeLP-her) is a low
      intensity, self-management program which has demonstrated efficacy in preventing
      excess weight gain in women. However, little is known about the implementation,
      reach, and sustainability of low-intensity prevention programs in rural settings,
      where risk for obesity in women is higher than urban settings. We aimed to
      evaluate a low-intensity healthy lifestyle program delivered to women in a rural
      setting to inform development of effective community prevention programs.
      METHODS: A mixed method hybrid implementation and evaluation study, guided by the
      RE-AIM framework (addressing the Reach, Effectiveness, Adoption, Implementation,
      and Maintenance), was undertaken. Data collection tools included anthropometric
      measures, program checklists, questionnaires, and semi-structured interviews with
      participants and local stakeholders. The RE-AIM self-audit tool was applied to
      assess evaluation rigor. RESULTS: Six hundred and forty-nine women from 41
      relatively socio-economic disadvantaged communities in Australia participated:
      mean age 39.6 years (+/-SD 6.7) and body mass index of 28.8 kg/m2 (+/-SD 6.9). A
      between-group weight difference of -0.92 kg (95% CI -1.67 to -0.16) showed
      program effectiveness. Reach was broad across 41 towns with 62% of participants
      reporting influencing some of the health behaviors of their families. Strong
      implementation fidelity was achieved with good retention rates at 1 year (76%)
      and high participant satisfaction (82% of participants willing to recommend this
      program). Over 300 multi-level community partnerships were established supporting
      high adoption. Stakeholders reported potential capacity to implement and sustain
      the prevention program in resource poor rural settings, due to the low-intensity
      design and minimal resources required. CONCLUSIONS: Our comprehensive RE-AIM
      evaluation demonstrates that an evidence-based obesity prevention program can be
      successfully implemented in real-world settings. The program achieved broad
      reach, effectiveness, and satisfaction at the community and stakeholder level,
      revealing potential for program sustainability. The evaluation addressed
      implementation knowledge gaps to support future obesity prevention program scale
      up. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN
      12612000115831 [ http://www.anzctr.org.au/ ].

PMID- 27881145
TI  - Evaluation of efficacy and efficiency of a pragmatic intervention by a social
      worker to support informal caregivers of elderly patients (The ICE Study): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Medical progress and the lifestyle modification have prolonged life
      expectancy, despite the development of chronic diseases. Support and care for
      older subjects are often provided by a network of informal caregivers composed of
      family, friends and neighbors, who are essential in helping older persons to
      continue living at home. It has been shown that the extent and diversity of
      informal tasks may jeopardize the physical, mental and social wellbeing of
      caregivers. METHODS/DESIGN: The aim of the Informal Carers of Elderly cohort is
      to define, through a longitudinal study, profiles of caregivers of older patients
      with a diagnosis of one of the following diseases: cancer (breast, prostate,
      colorectal), neurodegenerative diseases (Parkinson's disease, Alzheimer's disease
      and similar diseases), neurovascular diseases (stroke), sensory diseases (age
      related macular degeneration (AMD)) and heart disease (heart failure). Patients
      must be at least 60 years old and living in the region of Burgundy-Franche-Comte
      (France). By following the different phases of the caregiving relationship from
      the announcement of the diagnosis, it will be possible to assess the quality of
      life of caregivers, coping strategies, levels of anxiety and depression, social
      support and the extent of their burden. We will also evaluate the efficacy and
      efficiency of the implementation of a pragmatic intervention by a social worker
      to help informal caregivers, through a randomized interventional trial nested in
      the cohort. Qualitative approaches aimed at studying the caregiver/patient
      relationship, and situations leading to breakdown of the caregiver relationship
      will be also undertaken. DISCUSSION: Through an analytical and longitudinal
      definition of profiles of informal caregivers, this study will gather detailed
      information on their life courses and their health trajectory by identifying
      consequences associated with the concept of their role as carers. In addition,
      the randomized interventional trial will explore the relevance of the
      implementation of a supportive intervention by a social worker to help
      caregivers. These data will help to identify strategies that could be used to
      improve the existing sources of aid and to propose new approaches to help
      caregivers. This study will provide the opportunity to identify the most relevant
      means of support adapted to caregivers, and provide an impulse for new health
      care policies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02626377 .
      Retrospectively registered on 9 December 2015. Protocol date/version: 23 October
      2014/version 2.

PMID- 27881147
TI  - p53 predominantly regulates IL-6 production and suppresses synovial inflammation
      in fibroblast-like synoviocytes and adjuvant-induced arthritis.
AB  - BACKGROUND: Dominant-negative somatic mutations of p53 has been identified in the
      synovium of patients with rheumatoid arthritis (RA), in which interleukin (IL)-6
      has been established as a pivotal inflammatory cytokine. The aim of this study
      was to clarify the significance of p53 in the longstanding inflammation in RA by
      modulating IL-6. METHODS: We established adjuvant-induced arthritis (AIA) in
      Lewis rats and treated them with p53 activator, and then analyzed the
      histopathology of the synovium and IL-6 expression. Human fibroblast-like
      synoviocytes (FLS) were cultured and transfected with p53-siRNA or transduced
      with adenovirus (Ad)-p53, and then assessed with MTT, TUNEL staining, and
      luciferase assay. IL-1beta, tumor necrosis factor (TNF)-alpha and IL-17 were used
      to stimulate FLS, and subsequent IL-6 expression as well as relevant signal
      pathways were explored. RESULTS: p53 significantly reduced synovitis as well as
      the IL-6 level in the AIA rats. It controlled cell cycle arrest and
      proliferation, but not apoptosis. Proinflammatory cytokines inhibited p53
      expression in FLS, while p53 significantly suppressed the production of IL-6.
      Furthermore, IL-6 expression in p53-deficient FLS was profoundly reduced by NF
      kappaB, p38, JNK, and ERK inhibitors. CONCLUSION: Our findings reveal a novel
      function of p53 in controlling inflammatory responses and suggest that p53
      abnormalities in RA could sustain and accelerate synovial inflammation mainly
      through IL-6. p53 may be a key modulator of IL-6 in the synovium and plays a
      pivotal role in suppressing inflammation by interaction with the signal pathways
      in RA-FLS. Interfering with the p53 pathway could therefore be an effective
      strategy to treat RA.

PMID- 27881149
TI  - Antipsychotic prescribing patterns during and after critical illness: a
      prospective cohort study.
AB  - BACKGROUND: Antipsychotics are used to treat delirium in the intensive care unit
      (ICU) despite unproven efficacy. We hypothesized that atypical antipsychotic
      treatment in the ICU is a risk factor for antipsychotic prescription at
      discharge, a practice that might increase risk since long-term use is associated
      with increased mortality. METHODS: After excluding patients on antipsychotics
      prior to admission, we examined antipsychotic use in a prospective cohort of ICU
      patients with acute respiratory failure and/or shock. We collected data on
      medication use from medical records and assessed patients for delirium using the
      Confusion Assessment Method for the ICU. Using multivariable logistic regression,
      we analyzed whether age, delirium duration, atypical antipsychotic use, and
      discharge disposition (each selected a priori) were independent risk factors for
      discharge on an antipsychotic. We also examined admission Acute Physiology and
      Chronic Health Evaluation (APACHE) II score, haloperidol use, and days of
      benzodiazepine use in post hoc analyses. RESULTS: After excluding 18 patients due
      to prior antipsychotic use and three who withdrew, we included 500 patients.
      Among 208 (42%) treated with an antipsychotic, median (interquartile range) age
      was 59 (49-69) years and APACHE II score was 26 (22-32), characteristics that
      were similar among antipsychotic nonusers. Antipsychotic users were more likely
      than nonusers to have had delirium (93% vs. 61%, p < 0.001). Of the 208
      antipsychotic users, 172 survived to hospital discharge, and 42 (24%) of these
      were prescribed an antipsychotic at discharge. Treatment with an atypical
      antipsychotic was the only independent risk factor for antipsychotic prescription
      at discharge (odds ratio 17.6, 95% confidence interval 4.9 to 63.3; p < 0.001).
      Neither age, delirium duration, nor discharge disposition were risk factors (p =
      0.11, 0.38, and 0.12, respectively) in the primary regression model, and post hoc
      analyses found APACHE II (p = 0.07), haloperidol use (p = 0.16), and days of
      benzodiazepine use (p = 0.31) were also not risk factors for discharge on an
      antipsychotic. CONCLUSIONS: In this study, antipsychotics were used to treat
      nearly half of all antipsychotic-naive ICU patients and were prescribed at
      discharge to 24% of antipsychotic-treated patients. Treatment with an atypical
      antipsychotic greatly increased the odds of discharge with an antipsychotic
      prescription, a practice that should be examined carefully during medication
      reconciliation since these drugs carry "black box warnings" regarding long-term
      use.

PMID- 27881148
TI  - Susceptibility profile and metabolic mechanisms involved in Aedes aegypti and
      Aedes albopictus resistant to DDT and deltamethrin in the Central African
      Republic.
AB  - BACKGROUND: Aedes aegypti and Ae. albopictus are the main epidemic vectors of
      dengue, chikungunya and Zika viruses worldwide. Their control during epidemics
      relies mainly on control of larvae and adults with insecticides. Unfortunately,
      loss of susceptibility of both species to several insecticide classes limits the
      efficacy of interventions. In Africa, where Aedes-borne viruses are of growing
      concern, few data are available on resistance to insecticides. To fill this gap,
      we assessed the susceptibility to insecticides of Ae. aegypti and Ae. albopictus
      populations in the Central African Republic (CAR) and studied the mechanisms of
      resistance. METHODS: Immature stages were sampled between June and September 2014
      in six locations in Bangui (the capital of CAR) for larval and adult bioassays
      according to WHO standard procedures. We also characterized DDT- and pyrethroid
      resistant mosquitoes molecularly and biochemically, including tests for the
      activities of nonspecific esterases (alpha and beta), mixed-function oxidases,
      insensitive acetylcholinesterase and glutathione S-transferases. RESULTS: Larval
      bioassays, carried out to determine the lethal concentrations (LC50 and LC95) and
      resistance ratios (RR50 and RR95), suggested that both vector species were
      susceptible to Bacillus thuringiensis var. israeliensis and to temephos.
      Bioassays of adults showed susceptibility to propoxur and fenitrothion, except
      for one Ae. albopictus population that was suspected to be resistant to
      fenithrothion. None of the Ae. aegypti populations was fully susceptible to DDT.
      Ae. albopictus presented a similar profile to Ae. aegypti but with a lower
      mortality rate (41%). Possible resistance to deltamethrin was observed among Ae.
      aegypti and Ae. albopictus, although some were susceptible. No kdr mutations were
      detected in either species; however, the activity of detoxifying enzymes was
      higher in most populations than in the susceptible Ae. aegypti strain, confirming
      decreased susceptibility to DDT and deltamethrin. CONCLUSION: These findings
      suggested that regular, continuous monitoring of resistance is necessary in order
      to select the most effective adulticides for arbovirus control in Bangui.

PMID- 27881150
TI  - A metadata schema for data objects in clinical research.
AB  - BACKGROUND: A large number of stakeholders have accepted the need for greater
      transparency in clinical research and, in the context of various initiatives and
      systems, have developed a diverse and expanding number of repositories for
      storing the data and documents created by clinical studies (collectively known as
      data objects). To make the best use of such resources, we assert that it is also
      necessary for stakeholders to agree and deploy a simple, consistent metadata
      scheme. METHODS: The relevant data objects and their likely storage are
      described, and the requirements for metadata to support data sharing in clinical
      research are identified. Issues concerning persistent identifiers, for both
      studies and data objects, are explored. RESULTS: A scheme is proposed that is
      based on the DataCite standard, with extensions to cover the needs of clinical
      researchers, specifically to provide (a) study identification data, including
      links to clinical trial registries; (b) data object characteristics and
      identifiers; and (c) data covering location, ownership and access to the data
      object. The components of the metadata scheme are described. CONCLUSIONS: The
      metadata schema is proposed as a natural extension of a widely agreed standard to
      fill a gap not tackled by other standards related to clinical research (e.g.,
      Clinical Data Interchange Standards Consortium, Biomedical Research Integrated
      Domain Group). The proposal could be integrated with, but is not dependent on,
      other moves to better structure data in clinical research.

PMID- 27881151
TI  - Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial):
      study protocol for a randomised trial.
AB  - BACKGROUND: Gonorrhoea is a common sexually transmitted infection which causes
      genital pain and discomfort; in women it can also lead to pelvic inflammatory
      disease and infertility, and in men to epididymo-orchitis. Current treatment is
      with ceftriaxone, but there is increasing evidence of antimicrobial resistance
      which is reducing its effectiveness against gonorrhoea. A small, but increasing,
      number of patients have already been found to have highly resistant strains of
      gonorrhoea which has been associated with clinical failure. This trial aims to
      determine whether gentamicin is not clinically worse than ceftriaxone in the
      treatment of gonorrhoea. METHODS/DESIGN: This is a blinded, two-arm, multicentre,
      noninferiority randomised trial. Patients are eligible if they are aged 16-70
      years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion
      criteria are: known concurrent sexually transmitted infection(s) (excluding
      chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection;
      contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or
      lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight
      under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding
      28 days. Randomisation is to receive a single intramuscular injection of either
      gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as
      standard treatment. The estimated sample size is 720 participants (noninferiority
      limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all
      infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post
      treatment. Secondary outcomes include clinical resolution of symptoms, frequency
      of adverse events, tolerability of therapy, relationship between clinical
      effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae,
      and cost-effectiveness. DISCUSSION: The options for future treatment of
      gonorrhoea are limited. Results from this randomised trial will demonstrate
      whether gentamicin is not clinically worse than ceftriaxone for the treatment of
      gonorrhoea. This will inform clinical practice and policy for the treatment of
      gonorrhoea when current therapy with cephalosporins is no longer effective, or is
      contraindicated. TRIAL REGISTRATION: International Standard Randomised Controlled
      Trial Number - ISRCTN51783227 , Registered on 18 September 2014. Current protocol
      version 2.0 17 June 2015.

PMID- 27881152
TI  - Fitness and mobility training in patients with Intensive Care Unit-acquired
      muscle weakness (FITonICU): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Critical illness myopathy (CIM) and polyneuropathy (CIP) are a common
      complication of critical illness. Both cause intensive-care-unit-acquired (ICU
      acquired) muscle weakness (ICUAW) which increases morbidity and delays
      rehabilitation and recovery of activities of daily living such as walking
      ability. Focused physical rehabilitation of people with ICUAW is, therefore, of
      great importance at both an individual and a societal level. A recent systematic
      Cochrane review found no randomised controlled trials (RCT), and thus no
      supporting evidence, for physical rehabilitation interventions for people with
      defined CIP and CIM to improve activities of daily living. Therefore, the aim of
      our study is to compare the effects of an additional physiotherapy programme with
      systematically augmented levels of mobilisation with additional in-bed cycling
      (as the parallel group) on walking and other activities of daily living.
      METHODS/DESIGN: We will conduct a prospective, rater-masked RCT of people with
      ICUAW with a defined diagnosis of CIM and/or CIP in our post-acute hospital. We
      will randomly assign patients to one of two parallel groups in a 1:1 ratio and
      will use a concealed allocation. One intervention group will receive, in addition
      to standard ICU treatment, physiotherapy with systematically augmented levels of
      mobilisation (five times per week, over 2 weeks; 20 min each session; with a
      total of 10 additional sessions). The other intervention group will receive, in
      addition to standard ICU treatment, in-bed cycle sessions (same number, frequency
      and treatment time as the intervention group). Standard ICU treatment includes
      sitting balance exercise, stretching, positioning, and sit-to-stand training, and
      transfer training to get out of bed, strengthening exercise (in and out of bed),
      and stepping and assistive standing exercises. Primary efficacy endpoints will be
      walking ability (defined as a Functional Ambulation Category (FAC) level of >=3)
      and the sum score of the Functional Status Score for the Intensive Care Unit (FSS
      ICU) (range 0-22 points) assessed by a blinded tester immediately after 2 weeks
      of additional therapy. Secondary outcomes will include assessment of sit-to-stand
      recovery, overall limb strength (Medical Research Council, MRC) and grip
      strength, the Physical Function for the Intensive Care Unit Test-Scored (PFIT-S),
      the EuroQol 5 Dimensions (EQ-5D) questionnaire and the Reintegration to Normal
      Living Index (RNL-Index) assessed by a blinded tester. We will measure primary
      and secondary outcomes with blinded assessors at baseline, immediately after 2
      weeks of additional therapy, and at 3 weeks and 6 months and 12 months after the
      end of the additional therapy intervention. Based on our sample size calculation
      108 patients will be recruited from our post-acute ICU in the next 3 to 4 years.
      DISCUSSION: This will be the first RCT comparing the effects of two physical
      rehabilitation interventions for people with ICUAW due to defined CIP and/or CIM
      to improve walking and other activities of daily living. The results of this
      trial will provide robust evidence for physical rehabilitation of people with CIP
      and/or CIP who often require long-term care. TRIAL REGISTRATION: We registered
      the study on 6 April 2016 before enrolling the first patient in the trial at the
      German Clinical Trials Register ( www.germanctr.de ) with the identifier
      DRKS00010269 . This is the first version of the protocol (FITonICU study
      protocol).

PMID- 27881153
TI  - Verification of TREX1 as a promising indicator of judging the prognosis of
      osteosarcoma.
AB  - BACKGROUND: The study aimed to explore the correlation between the expression of
      TREX1 and the metastasis and the survival time of patients with osteosarcoma as
      well as biological characteristics of osteosarcoma cells for the prognosis
      judgment of osteosarcoma. METHOD: The correlation between the expression of TREX1
      protein and the occurrence of pulmonary metastasis in 45 cases of osteosarcoma
      was analyzed. The CD133+ and CD133- cell subsets of osteosarcoma stem cells were
      sorted by the flow cytometry. The tumorsphere culture, clone formation, growth
      curve, osteogenic and adipogenic differentiation, tumor-formation ability in nude
      mice, sensitivity of chemotherapeutic drugs, and other cytobiology behaviors were
      compared between the cell subsets in two groups; the expressions of stem cell
      related genes Nanog and Oct4 were compared; The expressions of TREX1 protein and
      mRNA were compared between the cell subsets in two groups. The data was
      statistically analyzed. The measurement data between the two groups were compared
      using t test. The count data between the two groups were compared using chi 2
      test and Kaplan-Meier survival analysis. A P value <0.05 indicated that the
      difference was statistically significant. RESULTS: The expression of TREX1
      protein in patients with osteosarcoma in the metastasis group was significantly
      lower than that in the non-metastasis group. The difference was statistically
      significant (P < 0.05). Up to the last follow-up visit, the former average
      survival time was significantly lower than that of the latter, and the difference
      was statistically significant (P < 0.05). The expression of TREX1 in human
      osteosarcoma CD133+ cell subsets was significantly lower than that in CD133- cell
      subsets. Stemness-related genes Nanog and Oct4 were highly expressed in human
      osteosarcoma CD133+ cell subsets with lower expression of TREX1; the biological
      characteristics identification experiment showed that human CD133+ cell subsets
      with low TREX1 expression could form tumorspheres, the number of colony forming
      was more, the cell proliferation ability was strong, the osteogenic and
      adipogenic differentiation potential was big, the tumor-forming ability in nude
      mice was strong, and the sensibility of chemotherapeutics drugs on cisplatin was
      low. CONCLUSIONS: The expression of TREX1 may be related to metastasis in
      patients with osteosarcoma. The expression of TREX1 was closely related to the
      cytobiology characteristics of osteosarcoma stem cell. TREX1 can play an
      important role in the occurrence and development processes. And, TREX1 is
      expected to become an effective new index for the evaluation of the prognosis.

PMID- 27881155
TI  - Selective laser trabeculoplasty for early glaucoma: analysis of success
      predictors and adjusted laser outcomes based on the untreated fellow eye.
AB  - BACKGROUND: To identify success predictors and to study the role of the fellow
      untreated eye as a co-variable for adjustment of intraocular pressure (IOP)
      outcomes following selective laser trabeculoplasty (SLT) in early open-angle
      glaucoma (OAG) patients. METHODS: A case series was carried out. Patients with
      uncontrolled early OAG or ocular hypertension (inadequate IOP control requiring
      additional treatment) underwent SLT (one single laser session) performed by the
      same surgeon in a standardized fashion. The same preoperative medical regimen was
      maintained during follow-up for all patients. Post-treatment assessments were
      scheduled at week 1 and months 1, 2, and 3. In order to account for possible
      influence of IOP fluctuation on laser outcomes, post-laser IOP values of the
      treated eye of each patient were also analyzed adjusting for IOP changes (between
      visits variation) of the untreated fellow eye (adjusted analysis). Pre and post
      laser IOP values were compared using paired t-test. Factors associated with the
      magnitude of IOP reduction were investigated using multiple regression analysis.
      RESULTS: A total of 45 eyes of 45 patients were enrolled. Mean IOP was reduced
      from 20.8 +/- 5.1 to 14.9 +/- 2.9 mmHg at month 3 (p < 0.001). Adjusted success
      rate (defined as IOP reduction >= 20%) was 64% and mean percentage of IOP
      reduction was 23.1 +/- 14.3% at last follow-up visit. Considering unadjusted post
      laser IOP values, it was found a 20% greater absolute IOP reduction (median
      [interquartile range] 6 mmHg [4-7] vs 5 mmHg [3-7]; p = 0.04), with a success
      rate of 76%. Although baseline IOP was significantly associated with both
      adjusted and unadjusted post-laser IOP reduction, a stronger association was
      found when unadjusted IOP values were considered (p < 0.001 and R 2 = 0.35; p <
      0.001 and R 2 = 0.67, respectively). Age, mean deviation (MD) index, central
      corneal thickness and type of glaucoma were not significant predictors (p >=
      0.150). CONCLUSIONS: In this group of patients with early OAG or ocular
      hypertension, our short-term results confirmed SLT as a safe and effective
      alternative for IOP reduction. Although better outcomes were found in eyes with
      higher preoperative IOP, this effect was mitigated when results were adjusted to
      the fellow untreated eye (to the influence of between visits-IOP fluctuations).

PMID- 27881154
TI  - Targeted next generation sequencing identifies novel NOTCH3 gene mutations in
      CADASIL diagnostics patients.
AB  - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts
      and leukoencephalopathy (CADASIL) is a monogenic, hereditary, small vessel
      disease of the brain causing stroke and vascular dementia in adults. CADASIL has
      previously been shown to be caused by varying mutations in the NOTCH3 gene. The
      disorder is often misdiagnosed due to its significant clinical heterogeneic
      manifestation with familial hemiplegic migraine and several ataxia disorders as
      well as the location of the currently identified causative mutations. The aim of
      this study was to develop a new, comprehensive and efficient single assay
      strategy for complete molecular diagnosis of NOTCH3 mutations through the use of
      a custom next-generation sequencing (NGS) panel for improved routine clinical
      molecular diagnostic testing. RESULTS: Our custom NGS panel identified nine
      genetic variants in NOTCH3 (p.D139V, p.C183R, p.R332C, p.Y465C, p.C597W, p.R607H,
      p.E813E, p.C977G and p.Y1106C). Six mutations were stereotypical CADASIL
      mutations leading to an odd number of cysteine residues in one of the 34 NOTCH3
      gene epidermal growth factor (EGF)-like repeats, including three new typical
      cysteine mutations identified in exon 11 (p.C597W; c.1791C>G); exon 18 (p.C977G;
      c.2929T>G) and exon 20 (p.Y1106C; c.3317A>G). Interestingly, a novel missense
      mutation in the CACNA1A gene was also identified in one CADASIL patient. All
      variants identified (novel and known) were further investigated using in silico
      bioinformatic analyses and confirmed through Sanger sequencing. CONCLUSIONS: NGS
      provides an improved and effective methodology for the diagnosis of CADASIL. The
      NGS approach reduced time and cost for comprehensive genetic diagnosis, placing
      genetic diagnostic testing within reach of more patients.

PMID- 27881156
TI  - Klotho sensitive regulation of dendritic cell functions by vitamin E.
AB  - BACKGROUND: Dendritic cells (DCs) are the most potent professional antigen
      presenting cells for naive T cells to link innate and acquired immunity. Klotho,
      an anti-aging protein, participates in the regulation of Ca2+ dependent migration
      in DCs. Vitamin E (VitE) is an essential antioxidant to protect cells from damage
      and elicits its inhibitory effects on NF-kappaB-mediated inflammatory response.
      However, the roles of VitE on mouse DC functions and the contribution of klotho
      to those effects both are unknown. The present study explored the effects of VitE
      on klotho expression, maturation, ROS production and migration in DCs. METHODS:
      The mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone
      marrow-derived DCs (BMDCs). Cells were stimulated with LPS (100 ng/ml) in the
      presence or absence of VitE (500 uM). RT-PCR and immunoprecipitation methods were
      employed to determine klotho expression, ELISA to determine cytokine release,
      flow cytometry to analyze number of CD86+CD11c+ cells, the intracellular
      expression of cytokines and reactive oxygen species (ROS) production and a
      transwell migration assay to trace migration. RESULTS: Klotho transcript level
      and this hormone secretion in DC supernatant were enhanced by VitE treatment and
      further increased in the presence of NF-kappaB inhibitor Bay 11-7082 (10 uM).
      Moreover, VitE treatment inhibited IL-12p70 protein expression of, ROS
      accumulation in and CCL21-dependent migration of LPS-triggered mature DCs, these
      effects were reversed following klotho silencing. CONCLUSION: The up-regulation
      of klotho by VitE could contribute to the inhibitory effects of VitE on NF-kappaB
      mediated DC functional maturation. The events might contribute to
      immunotherapeutic effect of VitE on the pathophysiology of klotho-related
      disease.

PMID- 27881157
TI  - Plasma microRNAs are associated with acute exacerbation in idiopathic pulmonary
      fibrosis.
AB  - BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has high
      short-term mortality with unknown causes. To predict this malignant condition in
      clinics is challenging. In this study, we aim to demonstrate whether there are
      miRNAs that differ between AE-IPF and stable IPF, which may be served as reliable
      biomarker for AE-IPF prediction. METHODS: Human fibrotic-associated miRNAs arrays
      were designed to detect miRNAs expression in plasma of 3 AE-IPF patients, 3
      Stable-IPF (S-IPF) patients and 3 normal controls (NC). Differentially expressed
      miRNAs between AE-IPF and S-IPF patients were selected for further analyses. The
      validation studies were carried out in plasma of 12 AE-IPF patients, 45 S-IPF
      patients and 51 healthy control subjects. Signaling pathways and cellular
      processes interacted with validated miRNAs were predicted by DIANA-miRPath.
      RESULTS: According to the array analysis, 6 miRNAs showed differentiated
      expression between AE-IPF and S-IPF patients (P < 0.05). In the validation
      studies, let-7d-5p was decreased in S-IPF and further decreased in AE-IPF, when
      compared to NC (0.0003 +/- 0.0002 vs 0.003 +/- 0.002, P < 0.01 and 0.0007 +/-
      0.0005 vs 0.003 +/- 0.002, P < 0.01). While miR-25-3p was obviously decreased in
      S-IPF (0.0002 +/- 0.0001 vs 0.0003 +/- 0.0003, P < 0.01) but significantly
      increased in AE-IP (0.0023 +/- 0.002 vs 0.0003 +/- 0.0003, P < 0.01). In receiver
      operator characteristic (ROC) curve analysis, the areas under the curve (AUCs) of
      miR-25-3p and let-7d-5p were 0.83 and 0.75, respectively. The sensitivity at
      fixed specificity of 90% was improved from 50% to 66.7% when the two miRNAs were
      combined. The functional prediction of miRNAs suggested that the loss of anti
      fibrotic capacity and the gain of uncontrolled cell growth may be required in AE
      IPF pathogenesis. CONCLUSIONS: In conclusion, miR-25-3p and let-7d-5p in plasma
      were differentially expressed between AE-IPF and S-IPF. A combination of these
      two miRNAs may be a potential biomarker for AE-IPF from IPF.

PMID- 27881158
TI  - Evaluation of daily patient positioning for radiotherapy with a commercial 3D
      surface-imaging system (CatalystTM).
AB  - BACKGROUND: To report our initial clinical experience with the novel surface
      imaging system CatalystTM (C-RAD AB, Sweden) in connection with an Elekta Synergy
      linear accelerator for daily patient positioning in patients undergoing radiation
      therapy. METHODS: We retrospectively analyzed the patient positioning of 154
      fractions in 25 patients applied to thoracic, abdominal, and pelvic body regions.
      Patients were routinely positioned based on skin marks, shifted to the calculated
      isocenter position and treated after correction via cone beam CT which served as
      gold standard. Prior to CBCT an additional surface scan by the CatalystTM system
      was performed and compared to a reference surface image cropped from the planning
      CT to obtain shift vectors for an optimal surface match. These shift vectors were
      subtracted from the vectors obtained by CBCT correction to assess the theoretical
      setup error that would have occurred if the patients had been positioned using
      solely the CatalystTM system. The mean theoretical set up-error and its standard
      deviation were calculated for all measured fractions and the results were
      compared to patient positioning based on skin marks only. RESULTS: Integration of
      the surface scan into the clinical workflow did not result in a significant time
      delay. Regarding the entire group, the mean setup error by using skin marks only
      was 0.0 +/- 2.1 mm in lateral, -0.4 +/- 2.4 mm in longitudinal, and 1.1 +/- 2.6
      mm vertical direction. The mean theoretical setup error that would have occurred
      using solely the CatalystTM was -0.1 +/- 2.1 mm laterally, -1.8 +/- 5.4 mm
      longitudinally, and 1.4 +/- 3.2 mm vertically. No significant difference was
      found in any direction. For thoracic targets the mean setup error based on the
      CatalystTM was 0.6 +/- 2.6 mm laterally, -5.0 +/- 7.9 mm longitudinally, and 0.5
      +/- 3.2 mm vertically. For abdominal targets, the mean setup error was 0.3 +/-
      2.2 mm laterally, 2.6 +/- 1.8 mm longitudinally, and 2.1 +/- 5.5 mm vertically.
      For pelvic targets, the setup error was -0.9 +/- 1.5 mm laterally, -1.7 +/- 2.8
      mm longitudinally, and 1.6 +/- 2.2 mm vertically. A significant difference
      between CatalystTM and skin mark based positioning was only observed in
      longitudinal direction of pelvic targets. CONCLUSION: Optical surface scanning
      using CatalystTM seems potentially useful for daily positioning at least to
      complement usual imaging modalities in most patients with acceptable accuracy,
      although a significant improvement compared to skin mark based positioning could
      not be derived from the evaluated data. However, this effect seemed to be rather
      caused by the unexpected high accuracy of skin mark based positioning than by
      inaccuracy using the CatalystTM. Further on, surface registration in longitudinal
      axis seemed less reliable especially in pelvic localization. Therefore further
      prospective evaluation based on strictly predefined protocols is needed to
      determine the optimal scanning approaches and parameters.

PMID- 27881159
TI  - Identifying profiles of service users in housing services and exploring their
      quality of life and care needs.
AB  - BACKGROUND: Housing services aim to support people with mental illness in their
      daily life and recovery. As the level of recovery differs between service users,
      the quality of life and care needs also might vary. However, the type and amount
      of care and support that service users receive do not always match their
      recovery. In order to improve the quality of care, this study aims to explore
      whether subgroups of service users exist based on three dimensions of recovery
      and to examine and compare the quality of life and care needs of the persons in
      these subgroups. METHODS: Latent class analysis was performed with data from 263
      service users of housing services in the Netherlands. Classes were based on three
      variables: personal recovery (Mental Health Recovery Measure), social recovery
      (Social Functioning Scale), and clinical recovery (Brief Symptom Inventory).
      Subsequently, the quality of life (MANSA) and care needs (CANSAS) of the
      different classes were analysed by the use of descriptive and inferential
      statistics. RESULTS: Three classes could be distinguished. Class 1 (45%)
      comprised of people who score the highest of the three classes in terms of
      personal and social recovery and who experience the least number of symptoms.
      People in class 2 (44%) and class 3 (11%) score significantly lower on personal
      and social recovery, and they experience significantly more symptoms compared to
      class 1. The distinction between class 2 and 3 can be made on the significantly
      higher number of symptoms in class 3. All three classes differ significantly on
      quality of life and unmet needs. CONCLUSIONS: The quality of life of service
      users of housing services needs improvement, as even persons in the best
      recovered subgroup have a lower quality of life than the average population.
      Workers of housing services need to be aware of the recovery of a client and what
      his or her individual needs and goals are. Furthermore, better care (allocation)
      concerning mental and physical health and rehabilitation is needed. Care should
      be provided on all dimensions of recovery at the same time, therefore mental
      health care organisations should work together and integrate their services.
      TRIAL REGISTRATION: ISRCTN registry ISRCTN77355880 retrospectively registered
      05/07/2013.

PMID- 27881160
TI  - Distribution and patterning of non-communicable disease risk factors in
      indigenous Mbororo and non-autochthonous populations in Cameroon: cross sectional
      study.
AB  - BACKGROUND: Data on Non-Communicable Diseases (NCDs) among indigenous populations
      are needed for interventions to improve health care. We conducted a survey in
      2013 among rural indigenous Mbororo, Fulbe and other ethnic groups to determine
      the distribution of risk factors of NCDs in Cameroon. METHODS: We selected seven
      targets of NCD risk factors: tobacco use, alcohol use, diet (salt/sugar intake,
      vegetable/fruit consumption), raised blood pressure, raised blood glucose,
      physical inactivity and weight measures. The WHO STEPwise approach was used to
      collect data from 1921 consenting participants aged >=20 years. Prevalence of NCD
      risk factors was summarised by descriptive statistics. RESULTS: Underweight was
      widespread, Mbororo (50.8%) and Fulbe (37.2%). Increase in prevalence of six risk
      factors was observed among the Fulbe when compared to Mbororo. Participants aged
      20-39 years had low levels of physical activity, poor diet and higher levels of
      alcohol consumption (except Mbororo) and those aged >=40 years had higher
      prevalence of diabetes, hypertension, current smoking and overweight/obesity. Men
      and women differed in current smoking, occasional/daily alcohol consumption, pre
      hypertension and hypertension, continuous walking for at least ten minutes, and
      weight measures for Fulbe and Mbororo, p < 0.05. CONCLUSION: Distribution of NCD
      risk factors was high among settled Fulani (Fulbe) when compared to indigenous
      nomadic Fulani (Mbororo). Change from nomadic to settled life might be
      accompanied by higher prevalence of NCDs. This data should be used to develop
      intervention programmes to curb the rising burden of NCDs in rural indigenous and
      non-indigenous populations.

PMID- 27881161
TI  - Lower hypoxic ventilatory response in smokers compared to non-smokers during
      abstinence from cigarettes.
AB  - BACKGROUND: Carotid body O2-chemosensitivity determines the hypoxic ventilatory
      response (HVR) as part of crucial regulatory reflex within oxygen homeostasis.
      Nicotine has been suggested to attenuate HVR in neonates of smoking mothers.
      However, whether smoking affects HVR in adulthood has remained unclear and
      probably blurred by acute ventilatory stimulation through cigarette smoke. We
      hypothesized that HVR is substantially reduced in smokers when studied after an
      overnight abstinence from cigarettes i.e. after nicotine elimination. METHODS: We
      therefore determined the isocapnic HVR of 23 healthy male smokers (age 33.9 +/-
      2.0 years, BMI 24.2 +/- 0.5 kg m-2, mean +/- SEM) with a smoking history of >8
      years after 12 h of abstinence and compared it to that of 23 healthy male non
      smokers matched for age and BMI. RESULTS: Smokers and non-smokers were comparable
      with regard to factors known to affect isocapnic HVR such as plasma levels of
      glucose and thiols as well as intracellular levels of glutathione in blood
      mononuclear cells. As a new finding, abstinent smokers had a significantly lower
      isocapnic HVR (0.024 +/- 0.002 vs. 0.037 +/- 0.003 l min-1 %-1BMI-1, P = 0.002)
      compared to non-smokers. However, upon re-exposure to cigarettes the smokers' HVR
      increased immediately to the non-smokers' level. CONCLUSIONS: This is the first
      report of a substantial HVR reduction in abstinent adult smokers which appears to
      be masked by daily smoking routine and may therefore have been previously
      overlooked. A low HVR may be suggested as a novel link between smoking and
      aggravated hypoxemia during sleep especially in relevant clinical conditions such
      as COPD.

PMID- 27881162
TI  - Residence-related factors and psychological distress among evacuees after the
      Fukushima Daiichi nuclear power plant accident: a cross-sectional study.
AB  - BACKGROUND: Relocation following a disaster can impact the psychological well
      being of evacuees. This study investigated the associations between residence
      related factors and psychological distress among evacuees living in temporary
      housing after the Fukushima Daiichi Nuclear Power Plant accident. METHODS: Data
      from 525 participants living in temporary housing were collected. Associations
      between residence-related factors (frequent relocation, dissatisfaction with the
      residence, and plan to move to permanent housing) and psychological distress were
      measured. The psychological distress of evacuees was measured using the Japanese
      version of the 6-item Kessler scale (K6). We used a cut-off score of five to
      identify cases with psychological distress, the basis of Kessler's 6 items for
      psychological distress. RESULTS: Multivariate logistic regression analysis (n =
      418) showed that frequent relocation (OR = 2.05, 95% CI: 1.14-3.66, p = 0.016)
      and dissatisfaction with the residence (OR = 2.48, 95% CI: 1.60-3.83, p < 0.001)
      was significantly associated with psychological distress. After stratifying by
      gender, dissatisfaction with the residence was associated with psychological
      distress, and a plan to move to permanent housing was significantly associated
      with psychological distress in women (OR = 1.93, 95% CI: 1.03-3.63, p = 0.041).
      CONCLUSIONS: Frequent relocation and dissatisfaction with the residence were
      associated with psychological distress among evacuees following the Fukushima
      nuclear disaster. Evacuees should be provided with comfortable living spaces, and
      steps should be taken to reduce repeated relocation of evacuees. Thus, particular
      attention should be paid to women with a plan to move to permanent housing within
      this context.

PMID- 27881164
TI  - Administration of anti-receptor activator of nuclear factor-kappa B ligand
      (RANKL) antibody for the treatment of osteoporosis was associated with
      amelioration of hepatitis in a female patient with growth hormone deficiency: a
      case report.
AB  - BACKGROUND: Growth hormone deficiency (GHD) is associated with non-alcoholic
      fatty liver disease (NAFLD). A recent animal study showed that hepatocyte
      specific receptor activator of nuclear factor-kappa B (RANK) knockout mice had
      significantly lower liver fat content compared with control mice concomitant with
      a decrease in production of inflammatory cytokines such as tumor necrosis factor
      alpha (TNF-alpha) from hepatocytes and kupffer cells. The role of anti-RANK
      ligand (RANKL) antibody for osteoporosis on hepatitis in patients with aGHD is
      still unknown. CASE PRESENTATION: A forty-seven-year-old female patient was
      referred to our hospital to investigate chronic hepatitis caused by unknown
      etiology. She had past history of craniopharyngioma treated with craniotomy and
      post-surgical radiotherapy. She was for the first time diagnosed as
      panhypopituitarism including growth hormone deficiency and osteoporosis by
      endocrine examinations and bone mineral densitometry, respectively. In addition,
      non-alcoholic steatohepatitis (NASH) was histologically confirmed by liver biopsy
      in this time. Sixty mg anti-RANKL antibody, which was subcutaneously injected to
      treat the osteoporosis every six months after replacement of 5 mg hydrocortisone
      and 30 MUg oral desmopressin, rapidly decreased the levels of her liver enzymes
      (ALT and gammaGTP were 133 to 72 U/L and 284 to 99 U/L at 16 months after the
      beginning of the treatment, respectively). Additional amelioration of liver
      dysfunction was not observed after growth hormone replacement. CONCLUSIONS: The
      clinical course of the present case suggested that RANKL-RANK signaling may be a
      key pathological mechanism in establishment or development of NAFLD or NASH in
      patients with panhypopituitarism including GHD.

PMID- 27881163
TI  - Assessing the feasibility of a web-based domestic violence intervention using
      chronic disease frameworks: reducing the burden of 'treatment' and promoting
      capacity for action in women abused by a partner.
AB  - BACKGROUND: Domestic violence shares many features with chronic disease,
      including ongoing physical and mental health problems and eroded self-efficacy.
      Given the challenges around help-seeking for women experiencing domestic
      violence, it is essential that they be given support to 'self-manage' their
      condition. The growing popularity of web-based applications for chronic disease
      self-management suggests that there may be opportunities to use them as an
      intervention strategy for women experiencing domestic violence, however, as yet,
      little is known about whether this might work in practice. DISCUSSION: It is
      critical that interventions for domestic violence-whether web-based or otherwise
      promote agency and capacity for action rather than adding to the 'workload' of
      already stressed and vulnerable women. Although randomised controlled trials are
      vital to determine the effectiveness of interventions, robust theoretical
      frameworks can complement them as a way of examining the feasibility of
      implementing an intervention in practice. To date, no such frameworks have been
      developed for the domestic violence context. Consequently, in this paper we
      propose that it may be useful to appraise interventions for domestic violence
      using frameworks developed to help understand the barriers and facilitators
      around self-management of chronic conditions. Using a case study of an online
      healthy relationship tool and safety decision aid developed in Australia (I
      DECIDE), this paper adapts and applies two theories: Burden of Treatment Theory
      and Normalisation Process Theory, to assess whether the intervention might
      increase women's agency and capacity for action. In doing this, it proposes a new
      theoretical model with which the practical application of domestic violence
      interventions could be appraised in conjunction with other evaluation frameworks.
      This paper argues that theoretical frameworks for chronic disease are appropriate
      to assess the feasibility of implementing interventions for domestic violence in
      practice. The use of the modified Burden of Treatment/Normalisation Process
      Theory framework developed in this paper strengthens the case for I-DECIDE and
      other web-based applications as a way of supporting women experiencing domestic
      violence.

PMID- 27881165
TI  - Comparative analysis of four terpenoids in root and cortex of Tripterygium
      wilfordii Radix by different drying methods.
AB  - BACKGROUND: Tripterygium wilfordii Radix, a well-known traditional medicine in
      china which is used for treatment of inflammation, pain, tumor and immune
      regulation for centuries in china, accompany with the serious toxic side effects.
      This study was carried out for simultaneously analyzing the four main components
      (triptolide, triptophenolide, demethylzeylasteral and celastrol) in Tripterygium
      wilfordii Radix under different drying processes, which was important for
      reducing the toxicity and quality control of Tripterygium wilfordii Radix in
      future. METHODS: The terpenes were extracted by using ultrasonic method with
      ethyl acetate from root or cortex of Tripterygium wilfordii Radix, and the
      sensitive and rapid HPLC-PDA method was developed for simultaneous quantification
      of triptolide, triptophenolide, demethylzeylasteral and celastrol in root and
      cortex of Tripterygium wilfordii Radix for evaluation of the impacts by different
      drying processes. RESULTS: The four compounds in their respective determined
      arrange had good linearity of 0.9998?R2?0.9999 and the average recoveries were
      range from 94.69 to 100.28%, RSDs were within 0.27 to 2.42%, respectively. The
      contents of triptolide, triptophenolide, demethylzeylasteral and celastrol in
      different Tripterygium wilfordii Radix individuals were varied greatly at
      different drying temperatures. Under different temperatures, the contents of
      triptolide, triptophenolide, demethylzeylasteral, and celastrol were 37.94-70.31
      mg/g, 0-1.807 mg/g, 0.3513-9.205 mg/g, 3.202-15.31 mg/g, respectively. The
      suitable drying temperature of terpenoids in root of wild and cultivate are 80 
      degrees C and 60  degrees C, the suitable drying temperature of terpenoids in
      cortex is 40  degrees C. CONCLUSIONS: The method established is high sensitivity,
      accuracy, reliability and suitable for the simultaneous analysis of terpenoids in
      Tripterygium wilfordii Radix. The data provide a scientific basis and reference
      for the quality control of herb and preparations related to Tripterygium
      wilfordii Radix.

PMID- 27881167
TI  - Differing association of alcohol consumption with different stroke types: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Whether light-to-moderate alcohol consumption is protective against
      stroke, and whether any association differs by stroke type, is controversial. We
      conducted a meta-analysis to summarize the evidence from prospective studies on
      alcohol drinking and stroke types. METHODS: Studies were identified by searching
      PubMed to September 1, 2016, and reference lists of retrieved articles.
      Additional data from 73,587 Swedish adults in two prospective studies were
      included. Study-specific results were combined in a random-effects model.
      RESULTS: The meta-analysis included 27 prospective studies with data on ischemic
      stroke (25 studies), intracerebral hemorrhage (11 studies), and/or subarachnoid
      hemorrhage (11 studies). Light and moderate alcohol consumption was associated
      with a lower risk of ischemic stroke, whereas high and heavy drinking was
      associated with an increased risk; the overall RRs were 0.90 (95 % CI, 0.85-0.95)
      for less than 1 drink/day, 0.92 (95 % CI, 0.87-0.97) for 1-2 drinks/day, 1.08 (95
      % CI, 1.01-1.15) for more than 2-4 drinks/day, and 1.14 (95 % CI, 1.02-1.28) for
      more than 4 drinks/day. Light and moderate alcohol drinking was not associated
      with any hemorrhagic stroke subtype. High alcohol consumption (>2-4 drinks/day)
      was associated with a non-significant increased risk of both hemorrhagic stroke
      subtypes, and the relative risk for heavy drinking (>4 drinks/day) were 1.67 (95
      % CI, 1.25-2.23) for intracerebral hemorrhage and 1.82 (95 % CI, 1.18-2.82) for
      subarachnoid hemorrhage. CONCLUSION: Light and moderate alcohol consumption was
      inversely associated only with ischemic stroke, whereas heavy drinking was
      associated with increased risk of all stroke types with a stronger association
      for hemorrhagic strokes.

PMID- 27881168
TI  - Loss of porin function in dopaminergic neurons of Drosophila is suppressed by
      Buffy.
AB  - BACKGROUND: Mitochondrial porin, also known as the voltage-dependent anion
      channel (VDAC), is a multi-functional channel protein that shuttles metabolites
      between the mitochondria and the cytosol and implicated in cellular life and
      death decisions. The inhibition of porin under the control of neuronal Ddc-Gal4
      result in short lifespan and in an age-dependent loss in locomotor function,
      phenotypes that are strongly associated with Drosophila models of Parkinson
      disease. METHODS: Loss of porin function was achieved through exploitation of RNA
      interference while derivative lines were generated by homologous recombination
      and tested by PCR. The UAS/Gal4 expression system was exploited with directed
      expression in neurons achieved with the use of the Dopa decarboxylase and in the
      developing eye with the Glass multiple reporter transgenes. Statistical analyses
      for ageing assay employed Log rank (Mantel-Cox) test, climbing indices were
      fitted with a non-linear curve and confidence intervals compared at 95%.
      Biometric analysis of the eye phenotypes was obtained by unpaired student T-test.
      RESULTS: The expression of alpha-synuclein in neuronal populations that include
      dopamine producing neurons under the control of Ddc-Gal4 produces a robust
      Parkinson disease model, and results in severely reduced lifespan and locomotor
      dysfunction. In addition, the porin-induced phenotypes are greatly suppressed
      when the pro-survival Bcl-2 homologue Buffy is overexpressed in these neurons and
      in the developing eye adding to the cellular advantages of altered expression of
      this anti-apoptotic gene. When we co-expressed alpha-synuclein along with porin,
      it results in a decrease in lifespan and impaired climbing ability. This
      enhancement of the alpha-synuclein-induced phenotypes observed in neurons was
      demonstrated in the neuron rich eye, where the simultaneous co-expression of
      porin-RNAi and alpha-synuclein resulted in an enhanced eye phenotype, marked by
      reduced number of ommatidia and increased disarray of the ommatidia. CONCLUSIONS:
      The inhibition of porin in dopaminergic neurons among others result in reduced
      lifespan and age-dependent loss in climbing ability, phenotypes that are
      suppressed by the overexpression of the sole pro-survival Bcl-2 homologue Buffy.
      The inhibition of porin phenocopies Parkinson disease phenotypes in Drosophila,
      while the overexpression of Buffy can counteract these phenotypes to improve the
      overall "healthspan" of the organism.

PMID- 27881169
TI  - Spatiotemporal exposure modeling of ambient erythemal ultraviolet radiation.
AB  - BACKGROUND: Ultraviolet B (UV-B) radiation plays a multifaceted role in human
      health, inducing DNA damage and representing the primary source of vitamin D for
      most humans; however, current U.S. UV exposure models are limited in spatial,
      temporal, and/or spectral resolution. Area-to-point (ATP) residual kriging is a
      geostatistical method that can be used to create a spatiotemporal exposure model
      by downscaling from an area- to point-level spatial resolution using fine-scale
      ancillary data. METHODS: A stratified ATP residual kriging approach was used to
      predict average July noon-time erythemal UV (UVEry) (mW/m2) biennially from 1998
      to 2012 by downscaling National Aeronautics and Space Administration (NASA) Total
      Ozone Mapping Spectrometer (TOMS) and Ozone Monitoring Instrument (OMI) gridded
      remote sensing images to a 1 km spatial resolution. Ancillary data were
      incorporated in random intercept linear mixed-effects regression models. Modeling
      was performed separately within nine U.S. regions to satisfy stationarity and
      account for locally varying associations between UVEry and predictors. Cross
      validation was used to compare ATP residual kriging models and NASA grids to UV-B
      Monitoring and Research Program (UVMRP) measurements (gold standard). RESULTS:
      Predictors included in the final regional models included surface albedo, aerosol
      optical depth (AOD), cloud cover, dew point, elevation, latitude, ozone, surface
      incoming shortwave flux, sulfur dioxide (SO2), year, and interactions between
      year and surface albedo, AOD, cloud cover, dew point, elevation, latitude, and
      SO2. ATP residual kriging models more accurately estimated UVEry at UVMRP
      monitoring stations on average compared to NASA grids across the contiguous U.S.
      (average mean absolute error [MAE] for ATP, NASA: 15.8, 20.3; average root mean
      square error [RMSE]: 21.3, 25.5). ATP residual kriging was associated with
      positive percent relative improvements in MAE (0.6-31.5%) and RMSE (3.6-29.4%)
      across all regions compared to NASA grids. CONCLUSIONS: ATP residual kriging
      incorporating fine-scale spatial predictors can provide more accurate, high
      resolution UVEry estimates compared to using NASA grids and can be used in
      epidemiologic studies examining the health effects of ambient UV.

PMID- 27881166
TI  - Using the social amoeba Dictyostelium to study the functions of proteins linked
      to neuronal ceroid lipofuscinosis.
AB  - Neuronal ceroid lipofuscinosis (NCL), also known as Batten disease, is a
      debilitating neurological disorder that affects both children and adults.
      Thirteen genetically distinct genes have been identified that when mutated,
      result in abnormal lysosomal function and an excessive accumulation of ceroid
      lipofuscin in neurons, as well as other cell types outside of the central nervous
      system. The NCL family of proteins is comprised of lysosomal enzymes (PPT1/CLN1,
      TPP1/CLN2, CTSD/CLN10, CTSF/CLN13), proteins that peripherally associate with
      membranes (DNAJC5/CLN4, KCTD7/CLN14), a soluble lysosomal protein (CLN5), a
      protein present in the secretory pathway (PGRN/CLN11), and several proteins that
      display different subcellular localizations (CLN3, CLN6, MFSD8/CLN7, CLN8,
      ATP13A2/CLN12). Unfortunately, the precise functions of many of the NCL proteins
      are still unclear, which has made targeted therapy development challenging. The
      social amoeba Dictyostelium discoideum has emerged as an excellent model system
      for studying the normal functions of proteins linked to human neurological
      disorders. Intriguingly, the genome of this eukaryotic soil microbe encodes
      homologs of 11 of the 13 known genes linked to NCL. The genetic tractability of
      the organism, combined with its unique life cycle, makes Dictyostelium an
      attractive model system for studying the functions of NCL proteins. Moreover, the
      ability of human NCL proteins to rescue gene-deficiency phenotypes in
      Dictyostelium suggests that the biological pathways regulating NCL protein
      function are likely conserved from Dictyostelium to human. In this review, I will
      discuss each of the NCL homologs in Dictyostelium in turn and describe how future
      studies can exploit the advantages of the system by testing new hypotheses that
      may ultimately lead to effective therapy options for this devastating and
      currently untreatable neurological disorder.

PMID- 27881172
TI  - Eigenspace-based beamformer using oblique signal subspace projection for
      ultrasound plane-wave imaging.
AB  - BACKGROUND: The Eigenspace-based beamformers, by orthogonal projection of signal
      subspace, can remove a large part of the noise, and provide better imaging
      contrast upon the minimum variance beamformer. However, wrong estimate of signal
      and noise component may bring dark-spot artifacts and distort the signal
      intensity. The signal component and noise and interference components are
      considered uncorrelated in conventional eigenspace-based beamforming methods. In
      ultrasound imaging, however, signal and noise are highly correlated. Therefore,
      the oblique projection instead of orthogonal projection should be taken into
      account in the denoising procedure of eigenspace-based beamforming algorithm.
      METHODS: In this paper, we propose a novel eigenspace-based beamformer based on
      the oblique subspace projection that allows for consideration of the signal and
      noise correlation. Signal-to-interference-pulse-noise ratio and an eigen
      decomposing scheme are investigated to propose a new signal and noise subspaces
      identification. To calculate the beamformer weights, the minimum variance weight
      vector is projected onto the signal subspace along the noise subspace via an
      oblique projection matrix. RESULTS: We have assessed the performance of proposed
      beamformer by using both simulated software and real data from Verasonics system.
      The results have exhibited the improved imaging qualities of the proposed
      beamformer in terms of imaging resolution, speckle preservation, imaging
      contrast, and dynamic range. CONCLUSIONS: Results have shown that, in ultrasound
      imaging, oblique projection is more sensible and effective than orthogonal
      subspace projection. Better signal and speckle preservation could be obtained by
      oblique projection compare to orthogonal projection. Also shadowing artifacts
      around the hyperechoic targets have been eliminated. Implementation the new
      subspace identification has enhanced the imaging resolution of the minimum
      variance beamformer due to the increasing the signal power in direction of
      arrival. Also it has offered better sidelobe suppression and a higher dynamic
      range.

PMID- 27881170
TI  - Relationship of cardiometabolic parameters in non-smokers, current smokers, and
      quitters in diabetes: a systematic review and meta-analysis.
AB  - BACKGROUND: Smoking is associated with increased macrovascular and microvascular
      complications in people with diabetes. In addition to other concomitant vascular
      perturbations, it also seems to influence the cardiometabolic parameters, which
      may partly explain the accelerated rate of vascular complications in smokers with
      diabetes. While smoking cessation is advocated as a universal component of the
      management of diabetes, there is some anecdotal evidence that HbA1c could
      increase following smoking cessation. The aim of this review is to explore the
      relationship between smoking and its cessation on cardiometabolic parameters in
      diabetes. METHODS: Searches were conducted on Medline, EMBASE and CINAHL up to
      March 2016. After screening 6866 studies (Additional file 1), 14 observational
      studies with a total of 98,978 participants' with either type 1 or type 2
      diabetes were selected for review. Narrative synthesis and meta-analyses were
      carried out to explore the relationship between smoking and its cessation.
      RESULTS: Meta-analysis showed that the pooled mean difference of HbA1c between
      non-smokers and smokers was -0.61% (95% CI -0.88 to -0.33, p < 0.0001). The
      difference in LDL cholesterol between non-smokers and smokers was -0.11 mmol/l
      (95% CI -0.21 to -0.01, p = 0.04). The difference in HDL cholesterol between non
      smokers and smokers was 0.12 mmol/l (95% CI 0.08-0.15, p < 0.001). However, there
      was no statistically significant difference in blood pressure between the two
      groups. The difference in HbA1c between quitters and continued smokers was not
      statistically significant -0.10% (95% CI -0.42 to 0.21, p = 0.53). However, a
      narrative synthesis revealed that over a period of 10 years, the HbA1c was
      comparable between non-smokers and quitters. CONCLUSION: Non-smokers have a
      statistically significant lower HbA1c and more favourable lipid profile compared
      to smokers. Smoking cessation does not lead to an increase in HbA1c in long-term
      and may reduce vascular complications in diabetes by its favourable impact on
      lipid profile.

PMID- 27881171
TI  - Assessment of left atrial mechanical functions and atrial electromechanical delay
      in Juvenile idiopathic arthritis by tissue Doppler echocardiography.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is a systemic chronic
      inflammatory disease. Studies using tissue Doppler imaging (TDI) for the
      evaluation of cardiac functions of children with JIA are limited. Thus, this
      study was conducted to evaluate Left ventricular function, left atrial mechanical
      functions and atrial electromechanical delay in JIA. METHODS: This study was
      carried out as a across sectional study. A total of 34 patients with active JIA
      and 34 controls were included. Atrial electromechanical delay and left atrial
      (LA) mechanical functions in addition to systolic and diastolic left ventricular
      (LV) functions were measured by using conventional echocardiography and TDI.
      Assessment of disease activity was done using Juvenile arthritis disease activity
      score (JADAS-27). RESULTS: JIA patients had abnormal atrial electromechanical
      coupling as established from prolonged lateral mitral annulus (PA lateral),
      septal mitral annulus (PA septum), inter-atrial and intra-atrial
      electromechanical delays compared with healthy controls. Left ventricular filling
      abnormalities were found characterized by a reduced E/A ratio (1.07 +/- 0.56 vs.
      1.48 +/- 0.16, p = 0.01). E/Em was significantly higher in patients with JIA
      (7.58 +/- 1.79 vs. 4.74 +/- 1.45, p = 0.003) denoting impaired diastolic
      function. Left atrial mechanical functions assessment showed significantly
      decreased LA passive emptying fraction, increased LA active emptying fraction and
      LA total emptying volume in JIA patients (p = 0.01, p = 0.01, p = 0.03
      respectively). CONCLUSION: Atrial electromechanical coupling intervals, and LA
      mechanical functions were impaired which can be considered as an early form of
      subclinical cardiac involvement in JIA patients. Significant diastolic functional
      abnormalities exist in JIA.

PMID- 27881174
TI  - Juvenile arthritis caused by a novel FAMIN (LACC1) mutation in two children with
      systemic and extended oligoarticular course.
AB  - BACKGROUND: The pathophysiological origin of juvenile idiopathic arthritis (JIA)
      is largely unknown. However, individuals with presumably pathogenic mutations in
      FAMIN have been reported, associating this gene with a rare subtype of this
      disorder. FAMIN, that is formerly also referred to as LACC1 or C13orf31, has
      recently been shown to play a crucial role in immune-metabolic functions and is
      involved in regulation of inflammasome activation and promotion of ROS
      production. CASE PRESENTATION: We describe two siblings with severe familial
      forms of juvenile arthritis in which whole-exome-sequencing revealed a novel
      homozygous frameshift mutation (NM_153218.2:c.827delC . p.(T276fs*2) in FAMIN.
      CONCLUSIONS: The observation of a new deleterious mutation adds further evidence
      that pathogenic mutations in FAMIN are causal for a monogenic form of JIA.
      Furthermore the associated phenotype is not restricted to systemic JIA, but can
      also be found in other forms of familial juvenile arthritis.

PMID- 27881173
TI  - Walkability and walking for transport: characterizing the built environment using
      space syntax.
AB  - BACKGROUND: Neighborhood walkability has been shown to be associated with walking
      behavior. However, the availability of geographical data necessary to construct
      it remains a limitation. Building on the concept of space syntax, we propose an
      alternative walkability index, space syntax walkability (SSW). This study
      examined associations of the full walkability index and SSW with walking for
      transport (WT). METHODS: Data were collected in 2003-2004 from 2544 adults living
      in 154 Census Collection Districts (CCD) in Adelaide, Australia. Participants
      reported past week WT frequency. Full walkability (consisting of net residential
      density, intersection density, land use mix, and net retail area ratio) and SSW
      (consisting of gross population density and a space syntax measure of street
      integration) were calculated for each CCD using geographic information systems
      and space syntax software. Generalized linear models with negative binomial
      variance and logarithmic link functions were employed to examine the associations
      of each walkability index with WT frequency, adjusting for socio-demographic
      variables. RESULTS: Two walkability indices were closely correlated (rho = 0.76,
      p < 0.01). The associations of full walkability and SSW with WT frequency were
      positive, with regression coefficients of 1.12 (95% CI: 1.08, 1.17) and 1.14 (95%
      CI: 1.10, 1.19), respectively. CONCLUSIONS: SSW employs readily-available
      geographic data, yet is comparable to full walkability in its association with
      WT. The concept and methods of space syntax provide a novel approach to further
      understanding how urban design influences walking behaviors.

PMID- 27881175
TI  - Do emergency medicine journals promote trial registration and adherence to
      reporting guidelines? A survey of "Instructions for Authors".
AB  - BACKGROUND: The aim of this study was to evaluate the current state of two
      publication practices, reporting guidelines requirements and clinical trial
      registration requirements, by analyzing the "Instructions for Authors" of
      emergency medicine journals. METHODS: We performed a web-based data abstraction
      from the "Instructions for Authors" of the 27 Emergency Medicine journals
      catalogued in the Expanded Science Citation Index of the 2014 Journal Citation
      Reports and Google Scholar Metrics h5-index to identify whether each journal
      required, recommended, or made no mention of the following reporting guidelines:
      EQUATOR Network, ICMJE, ARRIVE, CARE, CONSORT, STARD, TRIPOD, CHEERS, MOOSE,
      STROBE, COREQ, SRQR, SQUIRE, PRISMA-P, SPIRIT, PRISMA, and QUOROM. We also
      extracted whether journals required or recommended trial registration. Authors
      were blinded to one another's ratings until completion of the data validation.
      Cross-tabulations and descriptive statistics were calculated using IBM SPSS 22.
      RESULTS: Of the 27 emergency medicine journals, 11 (11/27, 40.7%) did not mention
      a single guideline within their "Instructions for Authors," while the remaining
      16 (16/27, 59.3%) mentioned one or more guidelines. The QUOROM statement and SRQR
      were not mentioned by any journals whereas the ICMJE guidelines (18/27, 66.7%)
      and CONSORT statement (15/27, 55.6%) were mentioned most often. Of the 27
      emergency medicine journals, 15 (15/27, 55.6%) did not mention trial or review
      registration, while the remaining 12 (12/27, 44.4%) at least mentioned one of the
      two. Trial registration through ClinicalTrials.gov was mentioned by seven (7/27,
      25.9%) journals while the WHO registry was mentioned by four (4/27, 14.8%).
      Twelve (12/27, 44.4%) journals mentioned trial registration through any registry
      platform. DISCUSSION: The aim of this study was to evaluate the current state of
      two publication practices, reporting guidelines requirements and clinical trial
      registration requirements, by analyzing the "Instructions for Authors" of
      emergency medicine journals. In this study, there was not a single reporting
      guideline mentioned in more than half of the journals. This undermines efforts of
      other journals to improve the completeness and transparency of research
      reporting. CONCLUSIONS: Reporting guidelines are infrequently required or
      recommended by emergency medicine journals. Furthermore, few require clinical
      trial registration. These two mechanisms may limit bias and should be considered
      for adoption by journal editors in emergency medicine. TRIAL REGISTRATION:
      UMIN000022486.

PMID- 27881177
TI  - High IKZF1/3 protein expression is a favorable prognostic factor for survival of
      relapsed/refractory multiple myeloma patients treated with lenalidomide.
AB  - The aim of this study is to assess nucleoprotein expression of IKZF1/3 in
      patients with relapsed/refractory multiple myeloma (MM) who received lenalidomide
      based therapy and correlated them with their clinical outcomes. A total of 50
      patients diagnosed with MM were entered in the study with the median follow-up of
      86.4 months. By immunohistochemistry (IHC), IKZF1 and IKZF3 were expressed in 72
      and 58% of the cases, respectively. IKZF1 and IKZF3 expressions were associated
      with longer median progression free survival (P = 0.0029 and P < 0.0001) and
      overall survival (P = 0.0014 and P < 0.0001). IKZF3 expression also appears
      predicted a favorable response to the lenalidomide-based therapy.

PMID- 27881176
TI  - No midterm advantages in the middle term using small intestinal submucosa and
      human amniotic membrane in Achilles tendon transverse tenotomy.
AB  - BACKGROUND: The study was aimed to compare the effects of small intestinal
      submucosa (SIS) and human amniotic membrane (HAM) on Achilles tendon healing.
      METHODS: A total of 48 New Zealand white rabbits were divided into two groups. A
      full-thickness transverse tenotomy was made at the right leg of the rabbits.
      Then, the laceration site was wrapped with HAM (P/A group) or SIS (P/S group).
      The ultimate stress (US) and Young's modulus (E) of the tendons were detected for
      biomechanical analysis. Histological evaluation was performed using hematoxylin
      and eosin, immunohistochemical, and immunofluorescent stain. Expression of
      collagen I was detected by western blot analysis, and levels of inflammatory
      cytokines IL-1beta, IL-6, and TNF-alpha were measured. Finally, adhesion
      formation was evaluated. RESULTS: There were no significant differences in
      filamentous adhesion, cross-sectional areas of the laceration sites, levels of
      inflammatory response, and collagen type I expression between the P/A and P/S
      groups (p > 0.05). Compared with the P/A group, the US and E values were
      significantly higher in the P/S group at day 7 (p < 0.05) and at day 14 (p <
      0.05). In addition, vascularity was significantly higher in the P/S group than
      that in the P/A group at day 3 (p < 0.05), day 7 (p < 0.01), and day 9 (p <
      0.05). CONCLUSIONS: SIS showed superior biomechanical properties and
      neovascularization over HAM in treatment of Achilles tendon injury in the early
      stage of healing.

PMID- 27881178
TI  - Measuring stress in medical education: validation of the Korean version of the
      higher education stress inventory with medical students.
AB  - BACKGROUND: Medical students face a variety of stressors associated with their
      education; if not promptly identified and adequately dealt with, it may bring
      about several negative consequences in terms of mental health and academic
      performance. This study examined psychometric properties of the Korean version of
      the Higher Education Stress Inventory (K-HESI). METHODS: The reliability and
      validity of the K-HESI were examined in a large scale multi-site survey involving
      7110 medical students. The K-HESI, Beck Depression Inventory (BDI) and questions
      regarding quality of life (QOL) and self-rated physical health (SPH) were
      administered. RESULTS: Exploratory factor analysis of the K-HESI identified seven
      factors: Low commitment; financial concerns; teacher-student relationship;
      worries about future profession; non-supportive climate; workload; and
      dissatisfaction with education. A subsequent confirmatory factor analysis
      supported the 7-factor model. Internal consistency of the K-HESI was satisfactory
      (Cronbach's alpha = .78). Convergent validity was demonstrated by its positive
      association with the BDI. Known group validity was supported by the K-HESI's
      ability to detect significant differences on the overall and subscale scores of K
      HESI according to different levels of QOL and SPH. CONCLUSIONS: The K-HESI is a
      psychometrically valid tool that comprehensively assesses various relevant
      stressors related to medical education. Evidence-based stress management in
      medical education empirically guided by the regular assessment of stress using
      reliable and valid measure is warranted.

PMID- 27881179
TI  - Molecular evidence of Sarcocystis nesbitti in water samples of Tioman Island,
      Malaysia.
AB  - BACKGROUND: Sarcocystis are intracellular protozoan parasites that are
      characterised by their ability to invade muscle tissue and form intramuscular
      sarcocysts. A muscular sarcocystosis outbreak was reported by travellers
      returning from Tioman Island in 2011 and 2012 where Sarcocystis nesbitti was
      identified as the main cause. The source of the S. nesbitti that was involved has
      remained elusive, although water is hypothesised to be the main cause of
      transmission. A surveillance study was therefore undertaken in the northern
      regions of Tioman Island to identify the source of S. nesbitti by screening
      rivers, water tanks, wells and seawater. METHODS: Water samples were collected
      from rivers, water tanks, wells and seawater on Tioman Island over the course of
      April to October 2015. Water samples were indirectly screened for Sarcocystis
      species by obtaining sediment from respective water sources. PCR amplification of
      the 18S rRNA gene region was conducted to identify positive samples. Microscopy
      was used in an attempt to reappraise PCR results, but no sporocysts were detected
      in any of the samples. RESULTS: A total of 157 water samples were obtained and 19
      were positive for various Sarcocystis species. Through BLASTn and phylogenetic
      analysis, these species were found to be S. singaporensis, S. nesbitti,
      Sarcocystis sp. YLL-2013 and one unidentified Sarcocystis species. CONCLUSIONS:
      This is the first positive finding of S. nesbitti in water samples on Tioman
      Island, which was found in a water tank and in river water samples. This finding
      supports the hypothesis that water was a potential medium for the transmission of
      S. nesbitti during the outbreak. This will potentially identify areas in which
      preventive measures can be taken to prevent future outbreaks.

PMID- 27881180
TI  - Polypharmacy and adverse outcomes after hip fracture surgery.
AB  - BACKGROUND: We aimed to explore the effects of polypharmacy and specific drug
      classes on readmissions and mortality after hip surgery. METHODS: We analyzed
      data on 272 consecutive hip fracture patients (72.1% females; age 82 +/- 9 years)
      who underwent acute hip replacement. We collected detailed data on the
      pharmacological treatment upon admission and discharge. Patients were followed up
      over a period of 6 months after discharge using the Swedish National Hospital
      Discharge Register and the Swedish National Cause of Death Register. RESULTS:
      After 6 months, 86 patients (31.6%) were readmitted, while 36 patients (13.2%)
      died. The total number of medications upon discharge was predictive of
      rehospitalization (odds ratio (OR) 1.08, 95%CI 1.01-1.17, p = 0.030) but not
      predictive of mortality. The use of antiosteoporotic agents (OR 1.86, 95%CI 1.06
      3.26, p = 0.03), SSRIs (OR 1.90, 95%CI 1.06-3.42, p = 0.03), and eye drops (OR
      4.12, 95%CI 1.89-8.97, p = 0.0004) were predictive of rehospitalization.
      Treatment with vitamin K antagonists (OR 4.29, 95%CI 1.19-15.39, p = 0.026),
      thiazides (OR 4.10, 95%CI 1.30-12.91, p = 0.016), and tramadol (OR 2.84, 95%CI
      1.17-6.90, p = 0.021) predicted readmissions due to a new fall/trauma.
      CONCLUSIONS: The total number of medications, use of antiosteoporotic agents,
      SSRIs, and eye drops predicted rehospitalization after hip fracture surgery,
      while use of vitamin K antagonists, thiazides, and tramadol was associated with
      readmissions due to a traumatic fall. TRIAL REGISTRATION: Hip fractures and
      polypharmacy in the elderly. Stimulus Project for the Elderly 2009-2011 (Reg no
      2009-11-26). Swedish National Board of Health and Welfare.

PMID- 27881181
TI  - Efficacy of ULV and thermal aerosols of deltamethrin for control of Aedes
      albopictus in nice, France.
AB  - BACKGROUND: Ultra-low volume (ULV) insecticidal aerosols dispensed from vehicle
      mounted cold-foggers are widely considered the method of choice for control of
      Aedes aegypti and Ae. albopictus during outbreaks of dengue and chikungunya and,
      more recently, Zika. Nevertheless, their effectiveness has been poorly studied,
      particularly in Europe. Nearly all published studies of ULV efficacy are bio
      assays based on the mortality of caged mosquitoes. In our study we preferred to
      monitor the direct impact of treatments on the wild mosquito populations. This
      study was undertaken to evaluate the efficiency of the two widely used space
      spraying methods to control Ae. albopictus and Ae. aegypti. METHODS: We
      determined the susceptibility of local Ae. albopictus to deltamethrin by two
      methods: topical application and the "WHO Tube Test". We used ovitraps baited
      with hay infusion and adult traps (B-G Sentinel) baited with a patented
      attractant to monitor the mosquitoes in four residential areas in Nice, southern
      France. The impact of deltamethrin applied from vehicle-mounted ULV fogging
      machines was assessed by comparing trap results in treated vs untreated areas for
      5 days before and 5 days after treatment. Four trials were conducted at the
      maximum permitted application rate (1 g.ha-1). We also made two small-scale tests
      of the impact of the same insecticide dispensed from a hand-held thermal fogger.
      RESULTS: Susceptibility to the insecticide was high but there was no discernable
      change in the oviposition rate or the catch of adult female mosquitoes, nor was
      there any change in the parous rate. In contrast, hand-held thermal foggers were
      highly effective, with more than 90% reduction of both laid eggs and females.
      CONCLUSIONS: We believe that direct monitoring of the wild mosquito populations
      gives a realistic assessment of the impact of treatments and suggest that the
      lack of efficacy is due to lack of interaction between the target mosquitoes and
      the ULV aerosol. We discuss the factors that influence the effectiveness of both
      methods of spraying in the context of epidemic situations.

PMID- 27881182
TI  - Research: Prevalence of neural tube defects Khartoum, Sudan August 2014-July
      2015.
AB  - BACKGROUND: Neural tube defects (NTDs) are birth defects that results from
      failure of the neural tube to develop properly during early pregnancy. METHODS:
      We studied the prevalence of neural tube defects in newborns admitted to the NICU
      in Soba University and Omdurman Maternity hospitals, during the period 1st August
      2014 to 31st July 2015. A cross-sectional hospital based study, involved all
      newborns with any type of neural tube defect admitted to the NICU in the study
      area during the study period. Data was collected using a questionnaire reviewing
      the medical, social history and clinical examination. RESULTS: Out of the 36,785
      delivered newborns during the study period, the prevalence of NTDs was 2.8:1000.
      Females were 56 (54.4%) predominated males 47 (45.6%). History of neural tube
      defects was found in 11 (10.7%) of the affected newborns siblings. Sixty-eight
      (66%) of the studied mothers received folic acid during pregnancy with the
      current child, of those who received folic acid 66 (97.1%) started folic acid
      after conception, 36 (54.5%) in the first trimester and 39 (57.4%) had no regular
      intake of the folic acid. The types of NTDs include myelomeningocele 49 (47.6%),
      anencephaly 18 (17.5%), encephalocele 14 (13.6%), myelomeningocele and
      hydrocephalus 11 (10.7%) and meningocele 8 (7.8%). CONCLUSION: The prevalence of
      neural tube defects is 2.8:1000. Myelomeningocele is the commonest encountered
      NTD. The use of preconception folic acid needs to be advocated.

PMID- 27881183
TI  - Erratum to: Recurrent purpura due to alcohol-related Schamberg's disease and its
      association with serum immunoglobulins: a longitudinal observation of a heavy
      drinker.

PMID- 27881184
TI  - StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): study
      protocol for a randomised controlled clinical trial.
AB  - BACKGROUND: The standard of care for neovascular age-related macular degeneration
      (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs
      targeting vascular endothelial growth factor (VEGF). The most commonly used anti
      VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of
      the STAR trial is to determine if stereotactic radiotherapy can reduce the number
      of anti-VEGF injections that patients with nAMD require. METHODS/DESIGN: STAR is
      a multicentre, double-masked, randomised, sham-controlled clinical trial. It
      evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to
      deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols
      participants with chronic, active nAMD. Participants receive a single SRT
      treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of
      0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and
      ranibizumab is administered at the visit if retreatment criteria are met. The
      primary outcome is the number of pro re nata ranibizumab injections during the
      first 24 months. Secondary outcomes include visual acuity, lesion morphology,
      quality of life and safety. Additional visits occur at 36 and 48 months to
      inspect for radiation retinopathy. The target sample size of 411 participants
      (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5
      injections against ranibizumab monotherapy, at 90% power, and a significance
      level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to
      detect non-inferiority of visual acuity at a five-letter margin. The primary
      analyses will be by intention to treat. DISCUSSION: The safety and efficacy
      outcomes will help determine the role of SRT in the management of chronic, active
      nAMD. TRIAL REGISTRATION: International Standard Randomised Controlled Trial
      Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov:
      NCT02243878 . Registered on 17 September 2014.

PMID- 27881186
TI  - The social network around influenza vaccination in health care workers: a cross
      sectional study.
AB  - BACKGROUND: Influenza vaccination coverage remains low among health care workers
      (HCWs) in many health facilities. This study describes the social network defined
      by HCWs' conversations around an influenza vaccination campaign in order to
      describe the role played by vaccination behavior and other HCW characteristics in
      the configuration of the links among subjects. METHODS: This study used cross
      sectional data from 235 HCWs interviewed after the 2010/2011 influenza
      vaccination campaign at the Hospital Clinic of Barcelona (HCB), Spain. The study
      asked: "Who did you talk to or share some activity with respect to the seasonal
      vaccination campaign?" Variables studied included sociodemographic
      characteristics and reported conversations among HCWs during the influenza
      campaign. Exponential random graph models (ERGM) were used to assess the role of
      shared characteristics (homophily) and individual characteristics in the social
      network around the influenza vaccination campaign. RESULTS: Links were more
      likely between HCWs who shared the same professional category (OR 3.13, 95% CI =
      2.61-3.75), sex (OR 1.34, 95% CI = 1.09-1.62), age (OR 0.7, 95% CI = 0.63-0.78
      per decade of difference), and department (OR 11.35, 95% CI = 8.17-15.64), but
      not between HCWs who shared the same vaccination behavior (OR 1.02, 95% CI = 0.86
      1.22). Older (OR 1.26, 95% CI = 1.14-1.39 per extra decade of HCW) and vaccinated
      (OR 1.32, 95% CI = 1.09-1.62) HCWs were more likely to be named. CONCLUSIONS:
      This study finds that there is no homophily by vaccination status in whom HCWs
      speak to or interact with about a workplace vaccination promotion campaign. This
      result highlights the relevance of social network analysis in the planning of
      health promotion interventions.

PMID- 27881188
TI  - A barrier to medical treatment? British medical practitioners, medical appliances
      and the patent controversy, 1870-1920.
AB  - From the late nineteenth century onwards there emerged an increasingly diverse
      response to escalating patenting activity. Inventors were generally supportive of
      legislation that made patenting more accessible, while others, especially
      manufacturers, saw patenting culture as an impediment. The medical profession
      claimed that patenting represented 'a barrier to medical treatment' and was thus
      detrimental to the nation's health, yet, as I argue, the profession's development
      of strict codes of conduct forbidding practitioners from patenting resulted in
      rebellion from some members, who increasingly sought protection for their
      inventions. Such polarized opinions within the medical trade continue to affect
      current medical practice today.

PMID- 27881185
TI  - Melatonin and melatonin agonists to prevent and treat delirium in critical
      illness: a systematic review protocol.
AB  - BACKGROUND: Delirium is a syndrome characterized by acute fluctuations and
      alterations in attention and arousal. Critically ill patients are at particularly
      high risk, and those that develop delirium are more likely to experience poor
      clinical outcomes such as prolonged duration of ICU and hospital length of stay,
      and increased mortality. Melatonin and melatonin agonists (MMA) have the
      potential to decrease the incidence and severity of delirium through their
      hypnotic and sedative-sparing effects, thus improving health-related outcomes.
      The objective of this review is to synthesize the available evidence pertaining
      to the efficacy and safety of MMA for the prevention and treatment of ICU
      delirium. METHODS: We will search Ovid MEDLINE, Web of Science, EMBASE, PsycINFO,
      the Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL to
      identify studies evaluating MMA in critically ill populations. We will also
      search http://apps.who.int/trialsearch for ongoing and unpublished studies and
      PROSPERO for registered reviews. We will not impose restrictions on language,
      date, or journal of publication. Authors will independently screen for eligible
      studies using pre-defined criteria; data extraction from eligible studies will be
      performed in duplicate. The Cochrane Risk of Bias Scale and the Newcastle-Ottawa
      Scale will be used to assess the risk of bias and quality of randomized and non
      randomized studies, respectively. Our primary outcome of interest is delirium
      incidence, and secondary outcomes include duration of delirium, number of
      delirium- and coma-free days, use of physical and chemical (e.g., antipsychotics
      or benzodiazepines) restraints, duration of mechanical ventilation, ICU and
      hospital length of stay, mortality, long-term neurocognitive outcomes, hospital
      discharge disposition, and adverse events. We will use Review Manager (RevMan) to
      pool effect estimates from included studies. We will present results as relative
      risks with 95% confidence intervals for dichotomous outcomes and as mean
      differences, or standardized mean differences, for continuous outcomes.
      DISCUSSION: Current guidelines make no pharmacological recommendations for either
      the prevention or treatment of ICU delirium. This systematic review will
      synthesize the available evidence on the efficacy and safety of MMA for this
      purpose, thus potentially informing clinical decision-making and improving
      patient outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024713.

PMID- 27881187
TI  - Class solutions for SABR-VMAT for high-risk prostate cancer with and without
      elective nodal irradiation.
AB  - BACKGROUND: The purpose of this study is to find the optimal planning settings
      for prostate SABR-VMAT for high-risk prostate cancer patients irradiated to
      prostate only (PO) or prostate and pelvic lymph nodes (PPLN). METHODS: For 10
      patients, plans using 6MV flattened, flattening-filter-free (FFF) 6MV (6 F) and
      FFF 10MV (10 F) photon beams with full and partial arc arrangements were
      generated and compared. The prescribed dose was 40Gy to the prostate with 25Gy to
      the PLN in 5 fractions. Plans were then evaluated for PTV coverage, dose fall
      off, and OAR doses. The number of monitor units and the treatment delivery times
      were also compared. Statistical differences were evaluated using a paired sample
      Wilcoxon signed rank test with a significance level of 0.05%. RESULTS: A total of
      150 plans were generated for this study. Acceptable PO plans were obtained using
      single arcs, while two arcs were necessary for PPLN. All plans were highly
      conformal (CI >=1.3 and CN >=0.90) with no significant differences in the PTV
      dose coverage. 6MV plans required significantly longer treatment time and had
      higher dose spillage compared to FFF plans. Superior plans were obtained using 10
      F 300 degrees  partial arcs for PO with the lowest rectal dose, dose spillage and
      the shortest treatment times. For PPLN, 6 F and 10 F plans were equivalent.
      CONCLUSIONS: SABR-VMAT with FFF photon beams offers a clear benefit with respect
      to shorter treatment delivery times and reduced dose spillage. Class solutions
      using a single 10 F 300 degrees  arc for PO and two 10 F or 6 F partial 300
      degrees  arcs for PPLN are proposed.

PMID- 27881189
TI  - Pharmaceutical patenting and the transformation of American medical ethics.
AB  - The attitudes of physicians and drug manufacturers in the US toward patenting
      pharmaceuticals changed dramatically from the mid-nineteenth century to the mid
      twentieth. Formerly, physicians and reputable manufacturers argued that
      pharmaceutical patents prioritized profit over the advancement of medical
      science. Reputable manufactures refused to patent their goods and most physicians
      shunned patented products. However, moving into the early twentieth century,
      physicians and drug manufacturers grew increasingly comfortable with the idea of
      pharmaceutical patents. In 1912, for example, the American Medical Association
      dropped the prohibition on physicians holding medical patents. Shifts in wider
      patenting cultures therefore transformed the ethical sensibilities of physicians.

PMID- 27881190
TI  - Trace element concentration in organic and conventional milk: what are the
      nutritional implications of the recently reported differences? - CORRIGENDUM.

PMID- 27881191
TI  - Policies for healthy and sustainable edible oil consumption: a stakeholder
      analysis for Thailand.
AB  - OBJECTIVE: Palm oil is a cheap and versatile edible oil in widespread use as a
      food ingredient that has been linked to negative health and environmental
      outcomes. The current study aimed to understand the prospects for future health
      focused policy development to limit food use of palm oil and promote a greater
      diversity of oils in Thailand's food system. DESIGN: Eighteen semi-structured
      interviews were conducted with a range of stakeholders. The interviews probed
      views on the economic, health and environmental dimensions of the issue, the
      prospects for health-focused policy development and the policy development
      process. Transcripts were analysed using a health policy analytical framework.
      SETTING: Thailand. SUBJECTS: Stakeholders from a range of ministries, regulatory
      agencies, the private sector, non-governmental organizations and academia.
      RESULTS: There are several impediments to the emergence of strong regulation,
      including the primacy of economic considerations in setting policy, doubt and
      misperception about health implications and a complex regulatory environment with
      little space for health-related considerations. At the same time, some sections
      of the food industry producing food for domestic consumption are substituting
      palm with other oils on the basis of consumer health perceptions. CONCLUSIONS:
      Strong regulation to curb the growth of palm oil is unlikely to emerge soon.
      However, a long-term strategy can be envisaged that relies on greater policy
      support for other indigenous oils, strategic rebalancing towards the use of palm
      oil for biofuels and oleochemicals, and harnessing Thailand's food technology
      capabilities to promote substitution in food production in favour of oils with
      healthier fatty acid composition.

PMID- 27881192
TI  - Effect of a ceiling fan ventilation system on finishing young bulls' health,
      behaviour and growth performance.
AB  - This research aimed at assessing the effects of a ceiling fan ventilation system
      on health, feeding, social behaviour and growth response of finishing young bulls
      fattened indoors during a mild summer season. A total of 69 Charolais young bulls
      were housed in six pens without any mechanical ventilation system (Control) and
      in six pens equipped with ceiling fans. The experimental period lasted 98 days
      from June until mid-September 2014. Four experimental days were considered in
      order to assess the effect of the ventilation system under two different
      microclimatic conditions: 2 alert days at monthly interval with temperature
      humidity index (THI) between 75 and 78, and 2 normal days with THI?74. Health and
      behaviour of the bulls were evaluated through 8-h observation sessions starting
      after morning feed delivery. The study was carried out during a rather cool
      summer with a climate average THI of 68.9 and 4 days with average THI>75. Despite
      these mild climate conditions, ceiling fans lowered litter moisture and acted as
      a preventive measure for bulls' dirtiness (odd ratio=47.9; 95% CI 19.6 to 117.4).
      The risk of abnormal breathing was increased for Control bulls (odd ratio=40.7;
      95% CI 5.4 to 304.2). When exposed to alert THI conditions, respiration rate and
      panting scores increased and rumination duration dropped in Control bulls
      compared with bulls provided with a ceiling fan. During observations under alert
      THI, bulls spent less time eating, more time being inactive and consumed more
      water compared with normal THI conditions. Bulls' daily dry matter intake
      measured during the observation sessions decreased on alert compared with normal
      THI days (P<0.001) due to a drop of intake during the daylight hours. Ceiling fan
      treatment had no effect on bulls' growth performance or water consumption but
      these results most likely depended on the mild climate conditions. Ceiling fans
      proved to mitigate some of the negative effects of heat stress on bulls'
      behaviour (rumination, lying down and drinking water) and respiration rate,
      however. The lack of a significant improvement of bulls' growth response should
      not discourage beef farmers from using ceiling fans in indoor systems,
      considering the likely increase in frequency and intensity of heat waves in the
      planet's temperate areas induced by global warming.

PMID- 27881193
TI  - Message framing in the context of the national menu-labelling policy: a
      comparison of public health and private industry interests.
AB  - OBJECTIVE: We conducted a content analysis of public comments to understand the
      key framing approaches used by private industry v. public health sector, with the
      goal of informing future public health messaging, framing and advocacy in the
      context of policy making. DESIGN: Comments to the proposed menu-labelling policy
      were extracted from Regulations.gov and analysed. A framing matrix was used to
      organize and code key devices and themes. Documents were analysed using content
      analysis with Dedoose software. SETTING: Recent national nutrition-labelling
      regulations in the USA provide a timely opportunity to understand message framing
      in relation to obesity prevention and policy. SUBJECTS: We examined a total of
      ninety-seven documents submitted on behalf of organizations (private industry, n
      64; public health, n 33). RESULTS: Public health focused on positive health
      consequences of the policy, used a social justice frame and supported its
      arguments with academic data. Industry was more critical of the policy; it used a
      market justice frame that emphasized minimal regulation, depicted its members as
      small, family-run businesses, and illustrated points with humanizing examples.
      CONCLUSIONS: Public health framing should counter and consider engaging directly
      with non-health-related arguments made by industry. Public health should include
      more powerful framing devices to convey their messages, including metaphors and
      humanizing examples.

PMID- 27881194
TI  - Authority and ownership: the growth and wilting of medicine patenting in Georgian
      England.
AB  - Secret, owned, Georgian medicines were normally known as patent medicines, though
      few had a current patent. Up to 1830, just 117 medicines had been patented,
      whilst over 1,300 were listed for taxation as 'patent medicines'. What were the
      benefits of patenting? Did medicine patenting affect consumer perception, and how
      was this used as a marketing tool? What were the boundaries of medical patenting?
      Patents for therapeutic preparations provided an apparent government guarantee on
      the source and composition of widely available products, while the patenting of
      medical devices seems to have been used to grant a temporary monopoly for the
      inventor's benefit.

PMID- 27881195
TI  - The involvement of RUNX2 and SPARC genes in the bacterial chondronecrosis with
      osteomyelitis in broilers.
AB  - Economic losses due to an increase of leg disorders in broilers have become a
      major concern of the poultry industry. Despite the efforts to reduce skeletal
      abnormalities in chickens, insufficient progress has been made. Bacterial
      chondronecrosis with osteomyelitis (BCO) is one of the main disorders that affect
      bone integrity in broilers. However, the genetic pathways and genes involved in
      most bone problems, including BCO, remains unclear. In this study, femoral
      samples from male broilers with 45 days of age affected or not with BCO were used
      to compare the relative expression with a reverse transcription real time PCR
      approach of 13 candidate genes: SPP1 (osteopontin), TNFRSF11B (osteoprotegerin),
      SPARC (osteonectin), CALB1 (calbidin 1), CALM (Calmodulin 2), IBSP
      (sialoprotein), COL1A2 (collagen, type I, alpha 2), BMP2 (bone morphogenetic
      protein 2), BMP3 (bone morphogenetic protein 3), RANKL (kappa-B nuclear factor
      ligand), SMAD1 (SMAD family member 1), LEPR (leptin receptor) and RUNX2 (related
      transcription factor Runt 2). Differential expression test between affected and
      non-affected groups was performed using the REST software. The RUNX2 and SPARC
      genes were downregulated (P<0.05) in the affected group, with reduced expression
      of fourfold when compared with the non-affected group. This result indicates that
      the downregulation of RUNX2 and SPARC can contribute to an increased incidence of
      BCO in broilers.

PMID- 27881196
TI  - Assessment of Reading Precursors in Spanish-Speaking Children.
AB  - This study's purpose was to analyse basic reading processes in different age
      groups of Spanish-speaking children using confirmatory factor analysis (CFA) and
      regression analysis. Two hundred forty-five children (aged 4 years and 9 months,
      to 9 years and 7 months; 120 boys, 125 girls), native Spanish-speakers, were
      selected from schools in Madrid. All participants were in either their last year
      of preschool or the first three years of elementary school, depending on their
      age. Nine classic reading tasks were created and administered to measure three
      reading skills: word recognition, phonological awareness, and reading
      comprehension. The results of the CFA show that data fit to proposed model with a
      general reading factor based on these three reading skills chi2(27) = 29.03, p =
      .36, RMSEA = .02, 90% CIs [.0, .05], CFI = 1.0. The word recognition skills were
      the best at describing reading performance in preschool children (R 2 = .51 for
      word identification task); phonological awareness, especially rhyme
      identification task, discriminated well until second grade (R 2 = .60); and
      finally, reading comprehension, basically phrase completion task, were the best
      measure of reading performance in third grade (R 2 = .45).

PMID- 27881197
TI  - Acceptability and Necessity of Training for Optimal Personal Protective Equipment
      Use.
AB  - Healthcare workers routinely self-contaminate even when using personal protective
      equipment. Observations of donning/ doffing practices on inpatient units along
      with surveys were used to assess the need for a personal protective equipment
      training program. In contrast to low perceived risk, observed doffing behaviors
      demonstrate significant personal protective equipment technique deficits. Infect
      Control Hosp Epidemiol 2017;38:226-229.

PMID- 27881198
TI  - Practical Experience with Hole-Free Phase Plates for Cryo Electron Microscopy.
AB  - Phase plate (PP) imaging has proven to be valuable in transmission cryo electron
      microscopy of unstained, native-state biological specimens. Many PP types have
      been described, however until the recent implementation of the "hole-free" phase
      plate (HFPP), imaging has been challenging. We found the HFPP to be simple to
      construct and to set up in the transmission electron microscopy, but care in
      implementing automated data collection is needed. Performance may be variable,
      both initially and over time, thus it is important to monitor and evaluate image
      quality by observing the power spectrum. We found that while some HFPPs gave
      transfer to high resolution without CTF oscillation, most reached high resolution
      when operated with modest defocus.

PMID- 27881200
TI  - Sow-level risk factors for stillbirth of piglets in organic sow herds.
AB  - In Danish organic pig production, one-third of total born piglets die before
      weaning, and stillbirth has previously crudely been estimated to account for 27%
      of the total preweaning mortality. The objective of this study was to evaluate
      season, litter size, parity and body condition of the sow as risk factors for
      stillbirth in nine commercial Danish organic pig herds. The study was conducted
      over a 1-year period, and the data included registrations on 5170 farrowings with
      82 906 total born piglets. The average number of total born piglets per litter
      was 16.0, and the number of stillborn piglets per litter was 1.1. A significant
      effect of season was seen with an odds ratio for stillbirth of 1.15 during summer
      (May to August) compared with the remaining part of the year. A non-linear effect
      of litter size was seen where an increase in litter size from 11 to 16 resulted
      in an odds ratio of stillbirth of 1.11. An increase in litter size from 16 to 21
      resulted in an odds ratio of stillbirth of 1.45. A significant interaction
      between body condition and parity was present. In first parity sows, an increase
      in body condition score from 2 (thin) to 3 (moderate) and from 3 to 4 (fat)
      increased the probability of stillbirth with an odds ratio of 1.23 and 1.36,
      respectively. In sows with parity above 4, an increase in body condition score
      from 2 to 3 and from 3 to 4 decreases the probability of stillbirth with an odds
      ratio of 0.68 and 0.79, respectively. In conclusion, increasing litter size and
      being born during the summer months of May to August were found to be risk
      factors for stillbirth. Furthermore, an interaction between body condition and
      parity showed that thin sows with parity above 4 had a substantially increased
      risk of stillbirth compared with normal and fat sows with parity above 4. In
      contrast, for parity 1 sows risk of stillbirth was increased in fat sows.

PMID- 27881199
TI  - Intestinal permeability induced by lipopolysaccharide and measured by lactulose,
      rhamnose and mannitol sugars in chickens.
AB  - Increased intestinal permeability (IP) can lead to compromised health. Limited in
      vivo IP research has been conducted in chickens. The objectives of the current
      study were to develop a model of increased IP utilizing lipopolysaccharide (LPS
      Escherichia coli O55:B5) and to evaluate IP changes using the lactulose, mannitol
      and rhamnose (LMR) sugar permeability test. In addition, fluorescein
      isothiocyanate dextran (FITC-d), d-lactate, zonula occludens (ZO-1) and diamine
      oxidase (DAO) permeability tests were employed. Male Ross chickens were reared
      until day 14 on the floor in an animal care facility and then transferred to
      individual cages in three separate experiments. In each of experiments 1 and 2,
      36 chicks were randomly allocated to receive either saline (control) or LPS
      (n=18/group). Lactulose, mannitol and rhamnose sugar concentration in blood was
      measured at 0, 30, 60, 90, 120 and 180 min in experiment 1, at 60, 90 and 120 min
      in experiment 2 and at 90 min in experiment 3 (n=16/group). Lipopolysaccharide
      was injected intraperitoneally at doses of 0.5, 1 and 1 mg/kg BW in experiments
      1, 2 and 3, respectively, on days 16, 18 and 20, whereas control received sterile
      saline. On day 21, only birds in experiments 1 and 2 were fasted for 19.5 h.
      Chicks were orally gavaged with the LMR sugars (0.25 gL, 0.05 gM, 0.05 gR/bird)
      followed by blood collection (from the brachial vein) as per time point for each
      experiment. Only in experiment 3, were birds given an additional oral gavage of
      FITC-d (2.2 mg/ml per bird) 60 min after the first gavage. Plasma d-lactate, ZO-1
      and DAO concentrations were also determined by ELISA in experiment 3 (n=10).
      Administration of LPS did not affect IP as measured by the LMR sugar test
      compared with control. This was also confirmed by FITC-d and DAO levels in
      experiment 3 (P>0.05). The plasma levels of d-lactate were decreased (P<0.05).
      Plasma levels of ZO-1 were increased in the third experiment only and did not
      change in the first two experiments. Lipopolysaccharide at doses of 0.5 and 1
      mg/kg did not increase IP in this model system. In conclusion, the LMR sugar can
      be detected in blood 90 min after the oral gavage. Further studies are needed for
      the applicability of LMR sugars tests.

PMID- 27881202
TI  - Association between junk food consumption and fast-food outlet access near school
      among Quebec secondary-school children: findings from the Quebec Health Survey of
      High School Students (QHSHSS) 2010-11.
AB  - OBJECTIVE: We investigated the association between junk food consumption at
      lunchtime (JCL) and fast-food outlet access near school among secondary-school
      children in Quebec. DESIGN: A geographic information system database was used to
      characterize the food environment around a sub-sample of 374 public schools in
      which 26 655 students were enrolled. The outcome variable was JCL during the
      previous week, dichotomized into low JCL (none or once) v. high JCL (twice or
      more). Access to fast-food outlets near school was assessed using an existing
      database of fast-food outlets in Quebec. Covariates included student (age, sex
      and self-rated perceived health), family (familial status and parental education)
      and school (urban/rural status and deprivation) variables. Hierarchical logistic
      regression models were employed for analyses using PROC GLIMMIX of SAS version
      9.3. SETTING: Province of Quebec, Canada. SUBJECTS: We used data from the Quebec
      Health Survey of High School Students (QHSHSS) 2010-11, a survey of secondary
      school Quebec students. RESULTS: Exposure to two or more fast-food outlets within
      a radius of 750 m around schools was associated with a higher likelihood of
      excess JCL (OR=1.50; 95 % CI 1.28, 1.75), controlling for the characteristics of
      the students, their families and their schools. CONCLUSIONS: The food environment
      surrounding schools can constitute a target for interventions to improve food
      choices among secondary-school children living in the province of Quebec.
      Transforming environments around schools to promote healthy eating includes
      modifying zoning regulations that restrict access to fast-food outlets around
      schools.

PMID- 27881201
TI  - Review: Feeding conserved forage to horses: recent advances and recommendations.
AB  - The horse is a non-ruminant herbivore adapted to eating plant-fibre or forage
      based diets. Some horses are stabled for most or the majority of the day with
      limited or no access to fresh pasture and are fed preserved forage typically as
      hay or haylage and sometimes silage. This raises questions with respect to the
      quality and suitability of these preserved forages (considering production,
      nutritional content, digestibility as well as hygiene) and required quantities.
      Especially for performance horses, forage is often replaced with energy dense
      feedstuffs which can result in a reduction in the proportion of the diet that is
      forage based. This may adversely affect the health, welfare, behaviour and even
      performance of the horse. In the past 20 years a large body of research work has
      contributed to a better and deeper understanding of equine forage needs and the
      physiological and behavioural consequences if these are not met. Recent nutrient
      requirement systems have incorporated some, but not all, of this new knowledge
      into their recommendations. This review paper amalgamates recommendations based
      on the latest understanding in forage feeding for horses, defining forage types
      and preservation methods, hygienic quality, feed intake behaviour, typical
      nutrient composition, digestion and digestibility as well as health and
      performance implications. Based on this, consensual applied recommendations for
      feeding preserved forages are provided.

PMID- 27881203
TI  - Validation of the Spanish Version of the School Engagement Measure (SEM).
AB  - The scientific study of school engagement has recently been the subject of
      considerable interest in the field of educational psychology, and significant
      advances have been made in our knowledge of this construct. For instance, there
      is currently consensus in the scientific community that it is multifaceted, and
      has three dimensions: behavioral engagement, emotional engagement, and cognitive
      engagement. However, more advanced statistical analyses are needed to validate
      Spanish-language measures of school engagement, which this study proposes to do.
      The sample was comprised of 1,250 adolescents from Basque Country (49% boys, 51%
      girls) aged 12 to 15 years old (M = 13.72, SD = 1.09). The results of
      confirmatory factor analysis on the School Engagement Measure (Fredricks,
      Blumenfeld, Friedel, & Paris, 2005) supported a three-dimensional structure of
      school engagement (chi2 (100) = 676.93, p < .001; GFI = .931; CFI = .906; IFI =
      .907; SRMR = .058; RMSEA = .068). Reliability indexes were satisfactory, ranging
      from .83 to .94. Adequate evidence of concurrent validity was found for the
      variable perceived school performance (p < .01). The results are discussed from
      an educational perspective, and with an eye to future research.

PMID- 27881204
TI  - The Longitudinal Emergency Medical Technician (EMT) Attributes and Demographics
      Study (LEADS): The First 10 Years and a Look at Public Perception of Emergency
      Medical Services (EMS).
AB  - Crowe RP , Bentley MA , Levine R . The Longitudinal Emergency Medical Technician
      (EMT) Attributes and Demographics Study (LEADS): the first 10 years and a look at
      public perception of Emergency Medical Services (EMS). Prehosp Disaster Med.
      2016;31(Suppl. 1):s1-s6.

PMID- 27881205
TI  - Hepatitis C Post-Exposure Prophylaxis for Healthcare Personnel: Policy Analysis
      Among Philadelphia's Large Teaching Institutions.

PMID- 27881206
TI  - Ultra-low-density genotype panels for breed assignment of Angus and Hereford
      cattle.
AB  - Angus and Hereford beef is marketed internationally for apparent superior meat
      quality attributes; DNA-based breed authenticity could be a useful instrument to
      ensure consumer confidence on premium meat products. The objective of this study
      was to develop an ultra-low-density genotype panel to accurately quantify the
      Angus and Hereford breed proportion in biological samples. Medium-density
      genotypes (13 306 single nucleotide polymorphisms (SNPs)) were available on 54
      703 commercial and 4042 purebred animals. The breed proportion of the commercial
      animals was generated from the medium-density genotypes and this estimate was
      regarded as the gold-standard breed composition. Ten genotype panels (100 to 1000
      SNPs) were developed from the medium-density genotypes; five methods were used to
      identify the most informative SNPs and these included the Delta statistic, the
      fixation (F st) statistic and an index of both. Breed assignment analyses were
      undertaken for each breed, panel density and SNP selection method separately with
      a programme to infer population structure using the entire 13 306 SNP panel
      (representing the gold-standard measure). Breed assignment was undertaken for all
      commercial animals (n=54 703), animals deemed to contain some proportion of Angus
      based on pedigree (n=5740) and animals deemed to contain some proportion of
      Hereford based on pedigree (n=5187). The predicted breed proportion of all
      animals from the lower density panels was then compared with the gold-standard
      breed prediction. Panel density, SNP selection method and breed all had a
      significant effect on the correlation of predicted and actual breed proportion.
      Regardless of breed, the Index method of SNP selection numerically (but not
      significantly) outperformed all other selection methods in accuracy (i.e.
      correlation and root mean square of prediction) when panel density was ?300 SNPs.
      The correlation between actual and predicted breed proportion increased as panel
      density increased. Using 300 SNPs (selected using the global index method), the
      correlation between predicted and actual breed proportion was 0.993 and 0.995 in
      the Angus and Hereford validation populations, respectively. When SNP panels
      optimised for breed prediction in one population were used to predict the breed
      proportion of a separate population, the correlation between predicted and actual
      breed proportion was 0.034 and 0.044 weaker in the Hereford and Angus
      populations, respectively (using the 300 SNP panel). It is necessary to include
      at least 300 to 400 SNPs (per breed) on genotype panels to accurately predict
      breed proportion from biological samples.

PMID- 27881207
TI  - Perceived Stress and Social Adaptation of the Primary Caregivers of Children with
      Intellectual Disabilities.
AB  - The study aimed to explore whether McCubbin and Patterson's Double ABCX model of
      stress and adaptation can promote a better understanding of the impacts of social
      support, definition of the stressor and coping strategies on stress and
      adaptation of the primary caregivers of Intellectually Disabled (ID) children
      above and beyond the effects of other factors. Structured Interview Schedule,
      Perceived Stress Scale (Keya, 2006) and Social Adjustment Scale (Mahmuda &
      Parvin, 2005) were administered on 130 caregivers of ID children and 140
      caregivers of typically developing children recruited conveniently. Findings
      reveal that stress and adaptation of the caregivers of ID children were
      significantly positively associated (r = .429, p < .01). Significant variations
      in stress and adaptation of the caregivers of ID children were found in terms of
      children's disability types (F = 14.50, df = 4/120, p < .001 for stress; F =
      11.92, df = 4/120, p < .001 for adaptation) and severity of disability (F = 5.21,
      df = 1/120, p < .05 for stress; F = 11.14, df = 1/120, p < .01 for adaptation).
      Factors of the Double ABCX model of stress and adaptation created significant
      variations in stress (F = 17.94, df = 3/121, p < .001) and adaptation (F = 9.96,
      df = 3/121, p < .001) of the caregivers of ID children above and beyond the
      effects of other factors. The findings suggest that the Double ABCX model is
      valuable in understanding stress and adaptation of the primary caregivers of ID
      children.

PMID- 27881208
TI  - The West Africa Disaster Preparedness Initiative: Strengthening National
      Capacities for All-Hazards Disaster Preparedness.
AB  - OBJECTIVE: The Ebola outbreak demonstrated the need for improved disaster
      response throughout West Africa. The West Africa Disaster Preparedness Initiative
      was a training and assessment effort led by US Africa Command and partners to
      strengthen capacities among 12 West African partner nations (PNs). METHODS:
      Series of 3-week training sessions with representatives from each PN were held
      from 13 July through 20 November 2015 at the Kofi Annan International
      Peacekeeping Training Centre in Accra, Ghana. A team conducted Disaster
      Management Capabilities Assessments (DMCAs) for each PN, including a review of
      key data, a survey for leaders, and in-person interviews of key informants.
      RESULTS: All 12 PNs generated a national Ebola Preparedness and Response Plan and
      Emergency Operations Center standard operating procedures. DMCA metrics were
      generated for each PN. Top performers included Ghana, with a plan rated
      good/excellent, and Benin and Burkina Faso, which both achieved a satisfactory
      rating for their plans. More than 800 people from 12 nations were trained.
      CONCLUSION: PNs have improved disaster management capabilities and awareness of
      their strengths and weaknesses. The Economic Community of West African States has
      increased its lead role in this and future planned initiatives. (Disaster Med
      Public Health Preparedness. 2017;11:431-438).

PMID- 27881210
TI  - The role of a food policy coalition in influencing a local food environment: an
      Australian case study.
AB  - OBJECTIVE: To explore how an Australian rural food policy coalition acts to
      influence a local food environment, focusing specifically on its composition,
      functions and processes as well as its food-related strategies and policy
      outputs. DESIGN: A qualitative case study approach was undertaken. Three sources
      were used to triangulate data: eleven semi-structured in-depth interviews with
      coalition members, analysis of thirty-seven documents relating to the coalition
      and observation at one coalition meeting. Data were analysed using a thematic and
      constant comparison approach. Community Coalition Action Theory provided a
      theoretical framework from which to interpret findings. SETTING: Two rural local
      government areas on the south-eastern coast of Victoria, Australia. SUBJECTS:
      Eleven members of the food policy coalition. RESULTS: Five themes emerged from
      the data analysis. The themes described the coalition's leadership processes,
      membership structure, function to pool resources for food system advocacy, focus
      on collaborative cross-jurisdictional strategies and ability to influence policy
      change. CONCLUSIONS: This Australian case study demonstrates that with strong
      leadership, a small-sized core membership and focus on collaborative strategies,
      food policy coalitions may be a mechanism to positively influence local food
      environments.

PMID- 27881209
TI  - Genetic parameters for lameness, mastitis and dagginess in a multi-breed sheep
      population.
AB  - The objective of the present study was to quantify the extent of genetic
      variation in three health-related traits namely dagginess, lameness and mastitis,
      in an Irish sheep population. Each of the health traits investigated pose
      substantial welfare implications as well as considerable economic costs to
      producers. Data were also available on four body-related traits, namely body
      condition score (BCS), live weight, muscle depth and fat depth. Animals were
      categorised as lambs (<365 days old) or ewes (?365 days old) and were analysed
      both separately and combined. After edits, 39 315 records from 264 flocks between
      the years 2009 and 2015 inclusive were analysed. Variance components were
      estimated using animal linear mixed models. Fixed effects included contemporary
      group, represented as a three-way interaction between flock, date of inspection
      and animal type (i.e. lamb, yearling ewe (i.e. females ?365 days but <730 days
      old that have not yet had a recorded lambing) or ewe), animal breed proportion,
      coefficients of heterosis and recombination, animal gender (lambs only), animal
      parity (ewes only; lambs were assigned a separate 'parity') and the difference in
      age of the animal from the median of the respective parity/age group. An additive
      genetic effect and residual effect were both fitted as random terms with maternal
      genetic and non-genetic components also considered for traits of the lambs. The
      direct heritability of dagginess was similar across age groups (0.14 to 0.15),
      whereas the direct heritability of lameness ranged from 0.06 (ewes) to 0.12
      (lambs). The direct heritability of mastitis was 0.04. For dagginess, 13% of the
      phenotypic variation was explained by dam litter, whereas the maternal
      heritability of dagginess was 0.05. The genetic correlation between ewe and lamb
      dagginess was 0.38; the correlation between ewe and lamb lameness was close to
      zero but was associated with a large standard error. Direct genetic correlations
      were evident between dagginess and BCS in ewes and between lameness and BCS in
      lambs. The present study has demonstrated that ample genetic variation exists for
      all three health traits investigated indicating that genetic improvement is
      indeed possible.

PMID- 27881212
TI  - Building machines that learn and think like people.
AB  - Recent progress in artificial intelligence has renewed interest in building
      systems that learn and think like people. Many advances have come from using deep
      neural networks trained end-to-end in tasks such as object recognition, video
      games, and board games, achieving performance that equals or even beats that of
      humans in some respects. Despite their biological inspiration and performance
      achievements, these systems differ from human intelligence in crucial ways. We
      review progress in cognitive science suggesting that truly human-like learning
      and thinking machines will have to reach beyond current engineering trends in
      both what they learn and how they learn it. Specifically, we argue that these
      machines should (1) build causal models of the world that support explanation and
      understanding, rather than merely solving pattern recognition problems; (2)
      ground learning in intuitive theories of physics and psychology to support and
      enrich the knowledge that is learned; and (3) harness compositionality and
      learning-to-learn to rapidly acquire and generalize knowledge to new tasks and
      situations. We suggest concrete challenges and promising routes toward these
      goals that can combine the strengths of recent neural network advances with more
      structured cognitive models.

PMID- 27881211
TI  - Analytical Multimode Scanning and Transmission Electron Imaging and Tomography of
      Multiscale Structural Architectures of Sulfur Copolymer-Based Composite Cathodes
      for Next-Generation High-Energy Density Li-S Batteries.
AB  - Poly[sulfur-random-(1,3-diisopropenylbenzene)] copolymers synthesized via inverse
      vulcanization represent an emerging class of electrochemically active polymers
      recently used in cathodes for Li-S batteries, capable of realizing enhanced
      capacity retention (1,005 mAh/g at 100 cycles) and lifetimes of over 500 cycles.
      The composite cathodes are organized in complex hierarchical three-dimensional
      (3D) architectures, which contain several components and are challenging to
      understand and characterize using any single technique. Here, multimode
      analytical scanning and transmission electron microscopies and energy-dispersive
      X-ray/electron energy-loss spectroscopies coupled with multivariate statistical
      analysis and tomography were applied to explore origins of the cathode-enhanced
      capacity retention. The surface topography, morphology, bonding, and compositions
      of the cathodes created by combining sulfur copolymers with varying 1,3
      diisopropenylbenzene content and conductive carbons have been investigated at
      multiple scales in relation to the electrochemical performance and physico
      mechanical stability. We demonstrate that replacing the elemental sulfur with
      organosulfur copolymers improves the compositional homogeneity and compatibility
      between carbons and sulfur-containing domains down to sub-5 nm length scales
      resulting in (a) intimate wetting of nanocarbons by the copolymers at interfaces;
      (b) the creation of 3D percolation networks of conductive pathways involving
      graphitic-like outer shells of aggregated carbons;

PMID- 27881215
TI  - Birth of an 'Asian cool' reference genome: AK1.
AB  - The human reference genome, maintained by the Genome Reference Consortium, is
      conceivably the most complete genome assembly ever, since its first construction.
      It has continually been improved by incorporating corrections made to the
      previous assemblies, thanks to various technological advances. Many currently
      ongoing population sequencing projects have been based on this reference genome,
      heightening hopes of the development of useful medical applications of genomic
      information, thanks to the recent maturation of high-throughput sequencing
      technologies. However, just one reference genome does not fit all the populations
      across the globe, because of the large diversity in genomic structures and
      technical limitations inherent to short read sequencing methods. The recent
      success in de novo construction of the highly contiguous Asian diploid genome
      AK1, by combining single molecule technologies with routine sequencing data
      without resorting to traditional clone-by-clone sequencing and physical mapping,
      reveals the nature of genomic structure variation by detecting thousands of novel
      structural variations and by finally filling in some of the prior gaps which had
      persistently remained in the current human reference genome. Now it is expected
      that the AK1 genome, soon to be paired with more upcoming de novo assembled
      genomes, will provide a chance to explore what it is really like to use ancestry
      specific reference genomes instead of hg19/hg38 for population genomics. This is
      a major step towards the furthering of genetically-based precision medicine. [BMB
      Reports 2016; 49(12): 653-654].

PMID- 27881213
TI  - Impact and Limitations of the 2015 National Health and Safety Network Case
      Definition on Catheter-Associated Urinary Tract Infection Rates.
AB  - Application of the new 2015 NHSN definition of catheter-associated urinary tract
      infection (CAUTI) in intensive care units reduced CAUTI rates by ~50%, primarily
      due to exclusion of candiduria. This significant reduction in CAUTI rates
      resulting from the changes in the definition must be considered when evaluating
      effectiveness of CAUTI prevention programs. Infect Control Hosp Epidemiol
      2017;38:239-241.

PMID- 27881214
TI  - Zinc(II) ion promotes anti-inflammatory effects of rhSOD3 by increasing cellular
      association.
AB  - Recently, we demonstrated that superoxide dismutase 3 (SOD3) is a strong
      candidate for biomedicine. Anti-oxidant function of SOD3 was accomplished without
      cell penetration, and it inhibited the inflammatory responses via non-enzymatic
      functions. SOD3 has the heparin binding domain associating cell surface.
      Interestingly, we found that Zn2+ promotes transduction effects of recombinant
      human SOD3 (rhSOD3) by increasing uptake via the heparin binding domain (HBD). We
      demonstrated an uptake of rhSOD3 from media to cell lysate via HBD, resulting in
      an accumulation of rhSOD3 in the nucleus, which was promoted by the presence of
      Zn2+. This resulted in increased inhibitory effects of rhSOD3 on NF-kB and STAT3
      signals in the presence of Zn2+, which shows elevated association of rhSOD3 into
      the cells. These results suggest that an optimized procedure can help to enhance
      the inflammatory efficacy of rhSOD3, as a novel biomedicine. [BMB Reports 2017;
      50(2): 85-90].

PMID- 27881217
TI  - Erratum to: From cell senescence to age-related diseases: differential mechanisms
      of action of senescence-associated secretory phenotypes.

PMID- 27881216
TI  - Interacting network of Hippo, Wnt/beta-catenin and Notch signaling represses
      liver tumor formation.
AB  - Acquiring a selective growth advantage by breaking the proliferation barrier
      established by gatekeeper genes is a centrally important event in tumor
      formation. Removal of the mammalian Hippo kinase Mst1 and Mst2 in hepatocytes
      leads to rapid hepatocellular carcinoma (HCC) formation, indicating that the
      Hippo signaling pathway is a critical gatekeeper that restrains abnormal growth
      in hepatocytes. By rigorous genetic approaches, we identified an interacting
      network of the Hippo, Wnt/beta-catenin and Notch signaling pathways that control
      organ size and HCC development. We found that in hepatocytes, the loss of Mst1/2
      leads to the activation of Notch signaling, which forms a positive feedback loop
      with Yap/Taz (transcription factors controlled by Mst1/2). This positive feedback
      loop results in severe liver enlargement and rapid HCC formation. Blocking the
      Yap/Taz-Notch positive feedback loop by Notch inhibition in vivo significantly
      reduced the Yap/Taz activities, hepatocyte proliferation and tumor formation.
      Furthermore, we uncovered a surprising inhibitory role of Wnt/beta-catenin
      signaling to Yap/Taz activities, which are important in tumor initiation. Genetic
      removal of beta-catenin in the liver of the Mst1/2 mutants significantly
      accelerates tumoriogenesis. Therefore, Wnt/beta-catenin signaling, known for its
      oncogenic property, exerts an unexpected function in restricting Yap/Taz and
      Notch activities in HCC initiation. The molecular interplay between the three
      signaling pathways identified in our study provides new insights in developing
      novel therapeutic strategies to treat liver tumors. [BMB Reports 2017; 50(1): 1
      2].

PMID- 27881219
TI  - RANK/RANKL Expression Is Induced by Cardiac Surgical Operation.
AB  - BACKGROUND: Cardiac surgery provokes a systemic inflammatory response in any
      patient. This complex body reaction involves also RANK/RANKL molecules which have
      been recently identified as principal regulators of bone metabolism. AIMS: To
      follow the changes in the expression of RANK/RANKL molecules on innate immune
      cells of cardiac surgical patients. PATIENTS AND METHODS: Twenty-six patients
      undergoing cardiac surgical were assigned to undergo coronary artery bypass
      grafting using either cardiopulmonary bypass ("on-pump") or modified
      "miniinvasive on-pump". The expression of RANK/RANKL was performed by flow
      cytometry. RESULTS: Significantly increased expression of RANK on monocytes of
      "miniinvasive on-pump" patients was found at the 1st, the 3nd, and 7th
      postoperative days. The similar pattern was found also for monocyte RANKL
      expression. In addition, RANKL expression was significantly increased at the 3rd
      postoperative day in "on-pump" patient. No significant differences between
      "miniinvasive on-pump" and "on-pump" cardiac surgical patients were found.
      CONCLUSION: The expression of both RANK and RANKL molecules is significantly
      enhanced on monocytes of "miniinvasive on-pump" cardiac surgical patients.

PMID- 27881222
TI  - How Serious Is Threat of Radiological Terrorism?
AB  - Radiological terrorism (radioterrorism) is the deliberate use of radiological
      weapons. These weapons use radioactive materials to disperse and emit ionizing
      radiation. There are two classes of radiological weapons - radiological dispersal
      devices (RDD) and radiation emission devices (RED). These weapons would no cause
      massive numbers of dead. In most radiological attack scenarios, only few people
      may die immediately or shortly after exposure to the ionizing radiation.
      Nevertheless, many people could develop cancer within several years to decade
      after the radiological weapon attack. Such attack might spur panic and result in
      high economic costs because of the need for decontamination and possible tearing
      down and reconstruction of contaminated structures. Thus, radiological weapons
      may be considered rather weapons of mass disruption than weapons threating of
      human life.

PMID- 27881226
TI  - Semiinvasive Aspergillosis: A Diagnosis to Consider in a Seemingly
      Immunocompetent Patient with a Pulmonary Nodule, Haemoptysis and Structural Lung
      Disease.
AB  - Semiinvasive pulmonary aspergillosis is an indolent form of pulmonary
      aspergillosis, which is seen mainly in patients who are mildly immunocompromised
      with underlying chronic lung diseases. This syndrome is rare, and the available
      literature is based on case reports and small case series. We describe here a
      patient with a semiinvasive aspergillosis associated with a probable idiopathic
      pulmonary fibrosis.

PMID- 27881227
TI  - Large Doubly Septated Concha Bullosa: An Unusual Anatomic Variation.
AB  - Partial or total pneumatization of the middle turbinate is called concha bullosa.
      It's one of the most common anatomic variations of the lateral nasal wall. The
      exact reason of such pneumatization is not known. It can originate from the
      frontal recess, middle meatus, sinus lateralis or, less frequently, from the
      posterior ethmoid cells. Concha bullosa remains usually asymptomatic. However, an
      extensively pneumatized middle turbinate may constitute space-occupying mass, and
      thus, it may cause nasal obstruction. We report an extremely rare case of a
      patient with a large, doubly septated concha bullosa with four different sources
      of aeration.

PMID- 27881229
TI  - An Assembly of Anomalous Extensor Tendons of the Hand - Anatomical Description
      and Clinical Relevance.
AB  - Innumerable descriptions about variations in the pattern of extensor tendons are
      recorded in the literature. The dorsum of the hand in an adult male cadaver
      revealed an unusual pattern of extensor arrangement during a gross anatomical
      practical session. The extensor digitorum, extensor indicis and extensor digiti
      minimi tendons displayed a variant pattern. Extensor digitorum contributed
      tendons only to the middle and ring fingers, with junctura tendinum present
      between the extensor digitorum for the ring finger and extensor digiti minimi.
      Interestingly, an accessory muscle was observed arising from the common extensor
      origin passing to the index finger, in addition to the usual extensor indicis.
      The origin and insertion of extensor digiti minimi was as usual with an accessory
      slip contributed from the extensor carpi ulnaris to the proximal phalanx of the
      fifth finger. The plethora of variations in this region is of paramount
      importance for the reconstructive surgeon, who may utilize the accessory tendons
      to restore functional capacity of the fingers.

PMID- 27881230
TI  - Summer music and arts festivals as hot spots for measles transmission: experience
      from England and Wales, June to October 2016.
AB  - We report 52 cases of measles linked to music and arts festivals in England and
      Wales, between mid-June and mid-October 2016. Nearly half were aged 15 to 19
      years. Several individuals who acquired measles at one festival subsequently
      attended another festival while infectious, resulting in multiple interlinked
      outbreaks. Transmission within festivals resulted in a geographical spread of
      cases nationally as well as internationally, which presents particular challenges
      for measles control.

PMID- 27881231
TI  - Burkholderia pseudomallei gamma-carbonic anhydrase is strongly activated by amino
      acids and amines.
AB  - Activation of the gamma-class carbonic anhydrase (CAs, EC 4.2.1.1) from the
      pathogenic bacterium Burkholderia pseudomallei (BpsgammaCA) with a series of
      natural and non-natural amino acids and aromatic/heterocyclic amines has been
      investigated. The best BpsgammaCA activators were d-His, l-DOPA, d-Trp, 4-amino-l
      Phe, dopamine, 2-(2-aminoethyl)pyridine, 2-aminoethyl-piparazine/morpholine and l
      adrenaline, which showed activation constants ranging between 9 and 86nM. The
      least effective activators were l-His, l-Phe and 2-pyridyl-methylamine, with KAs
      in the range of 1.73-24.7MUM. As little is known about the role of gamma-CAs in
      the lifecycle and virulence of this saprophytic bacterium, this study may shed
      some light on such phenomena. This is the first CA activation study of a gamma-CA
      from a pathogenic bacterium, the only other such study being on the enzyme
      discovered in the archaeon Methanosarcina thermophila, Cam.

PMID- 27881232
TI  - Serum copper, zinc, and iron levels, and markers of carbohydrate metabolism in
      postmenopausal women with prediabetes and type 2 diabetes mellitus.
AB  - The objective of the present study was to evaluate serum level of copper, zinc,
      iron and metabolic parameters in postmenopausal women with diabetes. A total of
      413 postmenopausal women were enrolled in the current study. Women were divided
      into 4 groups with equal age and body mass index according to glycated hemoglobin
      (HbA1c) levels (<=5.5; 5.5-6.0; 6.0-6.5; >6.5%). Serum Fe, Cu, and Zn levels were
      assessed using inductively-coupled plasma mass-spectrometry. Blood HbA1c, serum
      glucose, insulin, C-reactive protein (CRP), ferritin, and ceruloplasmin (Cp) were
      assessed using commercial kits. Homeostatic model assessment insulin resistance
      (HOMA-IR) and transferrin (Tf) saturation were calculated. The obtained data
      demonstrate that every 0.5% increase in HbA1c levels from 5.5% is associated with
      a significant elevation of glucose, insulin, CRP, and HOMA-IR values. Diabetic
      patients were characterized by significantly higher Fe (11%), Cu (8%), and Zn
      (6%) levels as compared to the controls. At the same time, the overall trend to
      increased metal levels in association with HbA1c was detected only for Fe
      (p<0.05) and Cu (p<0.05). Serum ferritin levels in diabetic women was 3-fold
      higher than in the controls, whereas Tf saturation was decreased by 35%. Serum Cp
      levels were significantly increased by 19% in prediabetes, whereas in diabetic
      postmenopausal women no such increase was observed. A significant elevation of
      total metal concentration in diabetic subjects without a concomitant elevation of
      transport proteins may be indicative of increased levels of "free" Fe and Cu,
      known to be toxic.

PMID- 27881234
TI  - DENSpm overcame Bcl-2 mediated resistance against Paclitaxel treatment in MCF-7
      breast cancer cells via activating polyamine catabolic machinery.
AB  - PURPOSE: The Bcl-2 mediated resistance is one of the most critical obstacle in
      cancer therapy. Conventional chemotherapeutics such as Paclitaxel, a commonly
      used in the treatment of metastatic breast cancer, is not sufficient to overcome
      Bcl-2 mediated drug resistance mechanism. Thus, combinational drug regimes are
      favored by researchers to overcome resistance phenotype against drugs. N1,N11
      diethylnorspermine (DENSpm), a polyamine analogue, which is a promising drug
      candidate induced-cell cycle arrest and apoptosis in various cancer cells such as
      prostate, melanoma, colon and breast cancer cells via activated polyamine
      catabolism and reactive oxygen generation. Recent studies indicated the potential
      therapeutic role of DENSpm in phase I and II trials in breast cancer cases.
      Although the molecular targets of Paclitaxel in apoptotic cell death mechanism is
      well documented, the therapeutic effect of DENSpm and Paclitaxel in breast cancer
      cells has not been investigated yet. In this study, our aim was to determine the
      time dependent effect of DENSpm and Paclitaxel on apoptotic cell death via
      determination of polyamine metabolism related targets in wt and Bcl-2
      overexpressing MCF-7 breast cancer cells. RESULTS: In our experimental study,
      Paclitaxel decreased cell viability in dose-dependent manner within 24h. Co
      treatment of Paclitaxel (30nM) with DENSpm (20MUM) further increased the
      cytoxicity of Paclitaxel (30nM) compared to alone Paclitaxel (30nM) treatment in
      MCF-7 Bcl-2+ breast cancer cells. In addition, we determined that resistance
      against Paclitaxel-induced apoptotic cell death in Bcl-2 overexpressed MCF-7
      cells was overcome due to activation of polyamine catabolic pathway, which caused
      depletion of polyamines. CONCLUSIONS: DENSpm combinational treatment might
      increase the effect of low cytotoxic paclitaxel in drug-resistant breast cancer
      cases.

PMID- 27881233
TI  - Do people with schizophrenia experience more negative emotion and less positive
      emotion in their daily lives? A meta-analysis of experience sampling studies.
AB  - Research on emotion experience in response to valenced stimuli has consistently
      shown that people with schizophrenia have the capacity to experience emotion.
      Specifically, people with schizophrenia report similar experiences to both
      positive and negative emotion-eliciting stimuli as individuals without the
      disorder. However, it is less clear if people with schizophrenia experience
      similar levels of positive emotion and negative emotion outside of standardized
      laboratory contexts, as in their daily lives. One reliable method for assessing
      emotion experience in schizophrenia has been the Experience Sampling Method
      (ESM), or Ecological Momentary Assessment (EMA). Using the PRISMA guidelines for
      meta-analysis, we reviewed the literature for all studies that included people
      with and without schizophrenia, and that included a positive or negative emotion
      assessment during participants' daily lives. The current study is a meta-analysis
      of 12 EMA studies of emotion experience, which included a total of 619 people
      with schizophrenia and 730 healthy controls. Results indicate that people with
      schizophrenia consistently report more negative and less positive emotion than
      healthy control participants. These findings differ from laboratory-based
      studies, which may be due to several factors, including environmental
      differences, effects of the disorder that appear more clearly in daily life, or
      additional concerns, such as depression, which has been shown to be related to
      negative emotion in schizophrenia. Importantly, these findings are in line with
      questionnaire-based measures of emotion experience, lending some support for
      their use in research and clinical settings.

PMID- 27881236
TI  - Deferasirox pharmacokinetics evaluation in a woman with hereditary
      haemochromatosis and heterozygous beta-thalassaemia.
AB  - We present the deferasirox pharmacokinetics evaluation of a female patient on
      iron chelation, for the interesting findings from her genetic background
      (hereditary haemochromatosis and heterozygous beta-thalassaemia) and clinical
      history (ileostomy; iron overload from transfusions). Drug plasma concentrations
      were measured by an HPLC-UV validated method, before and after ileum resection.
      Area under deferasirox concentration curve over 24h (AUC) values were determined
      by the mixed log-linear rule, using Kinetica software. AUC was low also with high
      deferasirox dose as well as tolerability. Non invasive tissue iron quantification
      by magnetic resonance imaging or superconducting quantum interference device were
      prevented by a metal hip replacement. Good efficacy and normalisation of iron
      markers was obtained on long term. Therapeutic drug monitoring in patient in
      critical conditions may help to understand reasons for non response and set
      individualised treatment.

PMID- 27881235
TI  - Elucidating the role of the FoxO3a transcription factor in the IGF-1-induced
      migration and invasion of uveal melanoma cancer cells.
AB  - Uveal melanoma (UM) is the most common primary intraocular malignant tumor of
      adults. It has high mortality rate due to liver metastasis. However, the
      epidemiology and pathogenesis of liver metastasis in UM are not elucidated and
      there is no effective therapy available for preventing the development of this
      disease. IGF-1 is a growth factor involved in cell proliferation, malignant
      transformation and inhibition of apoptosis. In previous report, IGF-1 receptor
      was found to be highly expressed in UM and this was related to tumor prognosis.
      FoxO3a is a Forkhead box O (FOXO) transcription factor and a downstream target of
      the IGF-1R/PI3K/Akt pathway involved in a number of physiological and
      pathological processes including cancer. However, the role of FoxO3a in UM is
      unknown. In the present study, we investigated fundamental mechanisms in the
      growth, migration and invasion of UM and the involvement of FoxO3a. IGF-1
      increased the cell viability, invasion, migration and S-G2/M cell cycle phase
      accumulation of UM cells. Western blot analysis showed that IGF-1 led to
      activation of Akt and concomitant phosphorylation of FoxO3a. FoxO3a
      phosphorylation was associated with its translocation into the cytoplasm from the
      nucleus and its functional inhibition led to the inhibition of expression of Bim
      and p27, but an increase in the expression of Cyclin D1. The effects of IGF-1 on
      UM cells were reversed by LY294002 (a PI3K inhibitor) or Akt siRNA, and the
      overexpression of FoxO3a also attenuated basal invasion and migration of UM.
      Taken all together, these results suggest that inhibition of FoxO3a by IGF-1 via
      the PI3K/Akt pathway has an important role in IGF-1 induced proliferation and
      invasion of UM cells. These findings also support FoxO3a and IGF signaling may
      represent a valid target for investigating the development of new strategies for
      the treatment and prevention of the pathology of UM.

PMID- 27881237
TI  - Exposure to traffic-related air pollution and risk of development of childhood
      asthma: A systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: The question of whether children's exposure to traffic
      related air pollution (TRAP) contributes to their development of asthma is
      unresolved. We conducted a systematic review and performed meta-analyses to
      analyze the association between TRAP and asthma development in childhood. DATA
      SOURCES: We systematically reviewed epidemiological studies published until 8
      September 2016 and available in the Embase, Ovid MEDLINE (R), and Transport
      databases. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: We
      included studies that examined the association between children's exposure to
      TRAP metrics and their risk of 'asthma' incidence or lifetime prevalence, from
      birth to age 18years old. STUDY APPRAISAL AND SYNTHESIS METHODS: We extracted key
      characteristics of each included study using a predefined data items template and
      these were tabulated. We used the Critical Appraisal Skills Programme checklists
      to assess the validity of each included study. Where four or more independent
      risk estimates were available for a continuous pollutant exposure, we conducted
      overall and age-specific meta-analyses, and four sensitivity analyses for each
      summary meta-analytic exposure-outcome association. RESULTS: Forty-one studies
      met our eligibility criteria. There was notable variability in asthma
      definitions, TRAP exposure assessment methods and confounder adjustment. The
      overall random-effects risk estimates (95% CI) were 1.08 (1.03, 1.14) per 0.5*10
      5m-1 black carbon (BC), 1.05 (1.02, 1.07) per 4MUg/m3 nitrogen dioxide (NO2),
      1.48 (0.89, 2.45) per 30MUg/m3 nitrogen oxides (NOx), 1.03 (1.01, 1.05) per
      1MUg/m3 Particulate Matter <2.5MUm in diameter (PM2.5), and 1.05 (1.02, 1.08) per
      2MUg/m3 Particulate Matter <10MUm in diameter (PM10). Sensitivity analyses
      supported these findings. Across the main analysis and age-specific analysis, the
      least heterogeneity was seen for the BC estimates, some heterogeneity for the
      PM2.5 and PM10 estimates and the most heterogeneity for the NO2 and NOx
      estimates. LIMITATIONS, CONCLUSIONS AND IMPLICATION OF KEY FINDINGS: The overall
      risk estimates from the meta-analyses showed statistically significant
      associations for BC, NO2, PM2.5, PM10 exposures and risk of asthma development.
      Our findings support the hypothesis that childhood exposure to TRAP contributes
      to their development of asthma. Future meta-analyses would benefit from greater
      standardization of study methods including exposure assessment harmonization,
      outcome harmonization, confounders' harmonization and the inclusion of all
      important confounders in individual studies. SYSTEMATIC REVIEW REGISTRATION
      NUMBER: PROSPERO 2014: CRD42014015448.

PMID- 27881239
TI  - Extreme Methemoglobinemia After Topical Benzocaine: Recognition by Pulse
      Oximetry.

PMID- 27881238
TI  - Rational identification of natural organic compounds to target the intermolecular
      interaction between Foxm and DNA in colorectal cancer.
AB  - The oncogenic transcription factor forkhead box M (Foxm) is overexpressed in
      human colorectal cancer (CRC). Targeting the protein interaction with its cognate
      DNA has been established as an attractive approach to anti-CRC chemotherapy.
      State-of-the-art molecular dynamics (MD) simulations revealed that the Foxm
      adopts considerably different conformations to interact with and without its DNA
      partner; the holo conformation is tightly packed as a typical globulin
      configuration, whereas the apo form is locally unstructured that exhibits
      intrinsic disorder in DNA recognition helix, indicating that DNA binding can help
      the Foxm refolding. With this finding, the MD equilibrium structure of DNA-free
      Foxm was utilized to perform molecular docking virtual screening against a
      natural organic compound library. Consequently, six hit compounds were identified
      as potential small-molecule mediators of Foxm-DNA interaction; their binding
      affinities (KD) to Foxm DNA-binding domain were then determined to range between
      3.8 and 230MUM by using isothermal titration calorimetry. These compounds were
      suggested to recognize and stabilize the apo conformation of Foxm, thus shifting
      the binding reaction equilibrium of Foxm from DNA-bound to DNA-free states to
      disrupt the formation of Foxm-DNA adduct.

PMID- 27881240
TI  - Risk factors for fatal and non-fatal child maltreatment in families previously
      investigated by CPS: A case-control study.
AB  - The objective of this study was to identify individual, family and caregiver risk
      factors for serious child maltreatment, resulting in hospitalization or death,
      among children and families investigated by Child Protective Services (CPS). We
      conducted a matched case-control study of 234 children who sustained fatal or
      serious nonfatal maltreatment due to physical abuse or neglect and whose mother
      was named in a CPS investigation between 1999 and 2013. A total of 702 children
      and their caregivers were included in the study with 234 cases matched
      2:1,resulting in 468 controls. Data on potential risk factors were abstracted
      from three county administrative databases. Differences between cases and
      controls were calculated and multivariable conditional logistic regression was
      used to estimate risk models. Variables associated with increased risk for
      serious maltreatment included male child gender,younger caregivers, three or more
      children under the age of 5 living in the home, families in which a biologic
      child was not living with either parent, and scoring moderate or high on the
      Structured Decision Making Risk Tool(r). Caregiver involvement in intimate
      partner violence (IPV) and child enrollment in public health insurance appears to
      mitigate the risk of serious maltreatment.

PMID- 27881241
TI  - Complications after use of elastomeric pressure-indicating media at 24-hour
      follow-up visit for immediate maxillary complete removable dental prosthesis: A
      clinical report.
AB  - Various pressure-indicating media are available to assess the adaptation of the
      intaglio surface of a removable dental prosthesis at the insertion and follow-up
      appointments. This clinical report describes the use of an elastomer that entered
      the maxillary sinus through an undetected oroantral communication at the 24-hour
      follow-up for an immediate maxillary complete removable dental prosthesis. A
      Caldwell-Luc sinusotomy procedure was required to remove the material, and the
      patient required over 1 year of healing time before his reported symptoms
      resolved.

PMID- 27881242
TI  - Atmospheric degradation of the organothiophosphate insecticide - Pirimiphos
      methyl.
AB  - The gas phase atmospheric degradation of pirimiphos-methyl (a widely used
      organophosphate insecticide and acaricide in many European regions) has been
      investigated at the large outdoor European Photoreactor (EUPHORE) in Valencia,
      Spain. Its photolysis has been studied under sunlight conditions and its reaction
      rate constant with OH radicals was measured by the relative rate method. The
      reaction with ozone was also investigated. The tropospheric degradation of
      pirimiphos-methyl is controlled mainly by the OH radical reaction. The rate
      coefficient of the OH reaction with pirimiphos-methyl, k, was measured by a
      conventional relative rate technique, where aniline was taken as a reference. The
      resulting value of the OH reaction rate constant with pirimiphos-methyl was
      k=(1.14+/-0.2)*10-10cm3molecule-1s-1. The tropospheric lifetime of pirimiphos
      methyl with respect to the reaction with OH radicals was estimated to be around
      1.6h (283+/-10) K and atmospheric pressure. Significant aerosol formation was
      observed in the OH reaction with yields that ranged from 25 to 37%, and with
      particle diameters below 550nm. This therefore reveals a high human risk due to
      PM<1, without taking into account the chemical composition of the degradation
      products. SO2, glyoxal and other oxygenated and nitrogenated compounds were the
      main degradation products detected.

PMID- 27881243
TI  - Early stage papillary thyroid carcinoma in developing country scenario - A
      different perspective.

PMID- 27881244
TI  - Negotiation: How to Be Effective.
AB  - The art of successful negotiation is not as random or difficult as it might seem
      at first glance. Most negotiations end up with both sides receiving something of
      value as well as giving up something valuable in return. It has been said that
      the best negotiated outcomes occur when both parties walk away a bit disappointed
      or just a little bit happy. The goal of this short primer is to give some hints
      as to how to get a slightly better deal than the other party most of the time.
      There are several points to remember to be able to achieve such an outcome
      frequently.

PMID- 27881245
TI  - The TRANSPLANTEX initiative.
AB  - TRANSPLANTEX, a French "investment for the future" initiated consortium of
      leading transplant units and research laboratories across France and a number of
      European countries aims to unravel, through mainly high-throughput genomics (and
      other omics) analyses of donor and recipients, novel (a) non-HLA,
      histocompatibility antigens, whether inside, or outside the MHC; (b) pre/post
      transplantation biomarkers. This shall lead to our better understanding of the
      pathophysiology of (and eventually designing better therapeutics for) the graft
      versus-host disease in hematopoietic cell transplants and that of chronic graft
      rejection after kidney transplant. Industrial developments as well as innovative
      teaching initiatives are also integral part of this program. The present issue of
      Human Immunology aims to present a first snapshot of some of the research
      performed by TRANPLANTEX partners.

PMID- 27881246
TI  - Referral for Kidney Transplantation and Indicators of Quality of Dialysis Care: A
      Cross-sectional Study.
AB  - BACKGROUND: Dialysis facility performance measures to improve access to kidney
      transplantation are being considered. Referral of patients for kidney
      transplantation evaluation by the dialysis facility is one potential indicator,
      but limited data exist to evaluate whether referral is associated with existing
      dialysis facility quality indicators. STUDY DESIGN: Cross-sectional study.
      SETTING & PARTICIPANTS: 12,926 incident (July 2005 to September 2011) adult (aged
      18-69 years) patients treated at 241 dialysis facilities with complete quality
      indicator information from US national registry data linked to transplantation
      referral data from all 3 Georgia kidney transplantation centers. FACTORS:
      Facility performance on dialysis quality indicators (high, intermediate, and low
      tertiles). OUTCOME: Percentages of patients referred within 1 year of dialysis
      therapy initiation at dialysis facility. RESULTS: Overall, a median of 25.4% of
      patients were referred for kidney transplantation within 1 year of dialysis
      therapy initiation. Higher facility-level referral was associated with better
      performance with respect to standardized transplantation ratio (high, 28.6%;
      intermediate, 25.1%; and low, 22.9%; P=0.001) and percentage waitlisted (high,
      30.7%; intermediate, 26.8%; and low, 19.2%; P<0.001). Facility-level referral was
      not associated with indicators of quality of care associated with dialysis
      therapy initiation, including percentage of incident patients being informed of
      transplantation options. For most non-transplantation-related indicators of high
      quality care, including those capturing mortality, morbidity, and anemia
      management, better performance was not associated with higher facility-level
      transplantation referral. LIMITATIONS: Potential ecologic fallacy and residual
      confounding. CONCLUSIONS: Transplantation referral among patients at dialysis
      facilities does not appear to be associated with overall quality of dialysis care
      at the facility. Quality indicators related to kidney transplantation were
      positively associated with, but not entirely correspondent with, higher
      percentages of patients referred for kidney transplantation evaluation from
      dialysis facilities. These results suggest that facility-level referral, which is
      within the control of the dialysis facility, may provide information about the
      quality of dialysis care beyond current indicators.

PMID- 27881247
TI  - Pain Management in CKD: A Guide for Nephrology Providers.
AB  - Although pain is one of the most commonly experienced symptoms by patients with
      chronic kidney disease, it is under-recognized, the severity is underestimated,
      and the treatment is inadequate. Pain management is one of the general primary
      palliative care competencies for medical providers. This review provides
      nephrology providers with basic skills for pain management. These skills include
      recognition of types of pain (nociceptive and neuropathic) syndromes and
      appropriate history-taking skills. Through this history, providers can identify
      clinical circumstances in which specialist referral is beneficial, including
      those who are at high risk for addiction, at risk for adverse effects to
      medications, and those with complicated care needs such as patients with a
      limited prognosis. Management of pain begins with the development of a shared
      treatment plan, identification of appropriate medications, and continual follow
      up and assessment of efficacy and adverse effects. Through adequate pain
      management, providers can positively affect the health of individual patients and
      the performance of health care systems.

PMID- 27881249
TI  - The present scope of Biomineralization.

PMID- 27881248
TI  - Communication about HIV and death: Maternal reports of primary school-aged
      children's questions after maternal HIV disclosure in rural South Africa.
AB  - INTRODUCTION: Children's understanding of HIV and death in epidemic regions is
      under-researched. We investigated children's death-related questions post
      maternal HIV-disclosure. Secondary aims examined characteristics associated with
      death-related questions and consequences for children's mental health. METHODS:
      HIV-infected mothers (N = 281) were supported to disclose their HIV status to
      their children (6-10 years) in an uncontrolled pre-post intervention evaluation.
      Children's questions post-disclosure were collected by maternal report, 1-2 weeks
      post-disclosure. 61/281 children asked 88 death-related questions, which were
      analysed qualitatively. Logistic regression analyses examined characteristics
      associated with death-related questions. Using the parent-report Child Behaviour
      Checklist (CBCL), linear regression analysis examined differences in total CBCL
      problems by group, controlling for baseline. RESULTS: Children's questions were
      grouped into three themes: 'threats'; 'implications' and 'clarifications'.
      Children were most concerned about the threat of death, mother's survival, and
      prior family deaths. In multivariate analysis variables significantly associated
      with asking death-related questions included an absence of regular remittance to
      the mother (AOR 0.25 [CI 0.10, 0.59] p = 0.002), mother reporting the child's
      initial reaction to disclosure being "frightened" (AOR 6.57 [CI 2.75, 15.70]
      p=<0.001) and level of disclosure (full/partial) to the child (AOR 2.55 [CI 1.28,
      5.06] p = 0.008). Controlling for significant variables and baseline, all
      children showed improvements on the CBCL post-intervention; with no significant
      differences on total problems scores post-intervention (beta -0.096 SE1.366 t = 
      0.07 p = 0.944). DISCUSSION: The content of questions children asked following
      disclosure indicate some understanding of HIV and, for almost a third of
      children, its potential consequence for parental death. Level of maternal
      disclosure and stability of financial support to the family may facilitate or
      inhibit discussions about death post-disclosure. Communication about death did
      not have immediate negative consequences on child behaviour according to maternal
      report. CONCLUSION: In sub-Saharan Africa, given exposure to death at young ages,
      meeting children's informational needs could increase their resilience.

PMID- 27881250
TI  - Opportunistic Risk Screening for Type 2 Diabetes: Exploring of Application of
      Diabetes Risk Assessment Tool in Community Pharmacy in Australia and Thailand.
AB  - OBJECTIVE: To evaluate the feasibility of providing diabetes risk assessment at
      community pharmacy level in Australia and Thailand from organizational aspects.
      METHODS: The intervention study was conducted in eight community pharmacies in
      New South Wales, Australia, and six community pharmacies in Central Thailand.
      Diabetes risk assessment tools were applied to determine the risk of developing
      type 2 diabetes. An open-ended question was asked to solicit the willingness-to
      pay value for the service. A semistructured interview was conducted with
      participating pharmacists to solicit the perceived facilitators and barriers in
      providing the service. RESULTS: There were a total of 132 and 185 participants,
      with the ratio of participants in the three risk categories of low, intermediate,
      and high being 1:4:11 and 2:1:1.5 for Australia and Thailand, respectively. More
      Thai participants were willing to pay for the service (72.4% vs. 18.9%; P =
      0.0001). Pharmacists from both countries agreed that providing risk assessment
      would increase health awareness and assist in dampening the burden of disease. A
      major barrier is time and staff shortage. Support from the government and
      collaboration among health care providers were major facilitators from Thai
      pharmacists' perspective, whereas remuneration was a major facilitator from
      Australian pharmacists' perspective. CONCLUSIONS: Pharmacists in both countries
      agreed that this intervention would contribute to produce positive health
      benefits. Differences in advantages and barriers as well as in the proportion of
      consumers willing to pay for the service demonstrated that it is essential for
      pharmacists (particularly in developing countries) to be aware of the pitfalls of
      copying practice initiatives in developed countries without any consideration of
      the local health care environment.

PMID- 27881252
TI  - Pharmacoeconomic and Outcomes Research are steadily moving forward in Asia.

PMID- 27881251
TI  - Comparison of Health Care Utilization and Costs for Patients with Asthma by
      Severity and Health Insurance in Thailand.
AB  - BACKGROUND: To compare health care utilization and cost by asthma severity and
      type of health insurance in Thailand. METHODS: A retrospective cohort study using
      an electronic database was conducted in patients with asthma. Patients who were
      diagnosed with asthma from 2009 to 2011, had at least two subsequent health care
      encounters for asthma during the first six months after the first asthma
      diagnosis, and had at least 90 days of follow-up were included. The primary
      outcome was direct health care costs of inpatient and outpatient care. We
      compared outcomes between groups on the basis of a proxy of severity
      (mild/moderate severe asthma vs. high severe asthma) and type of health insurance
      using a multivariable generalized linear model. Covariates such as Patients'
      demographic characteristics, comorbidities, and concurrent medications were
      included in the model. RESULTS: Among 1982 patients included, the average age was
      40.3 +/- 24.0 years, with 60.7% being males. A total of 1936 patients had
      mild/moderate severe asthma, whereas 46 patients had high severe asthma. There
      were 1293 patients under the Universal Coverage Scheme, 264 patients under Social
      Security Insurance, and 626 patients under the Civil Servant Medical Benefit
      Scheme (CSMBS). The average annual cost per patient was $598 +/- $871. In
      adjusted analyses, the health care cost of patients with high severe asthma was
      $71 higher than that of patients with mild/moderate severe asthma (95% confidence
      interval $-131 to $274). The cost of patients under the CSMBS was $110 (95%
      confidence interval $29-$191) higher than that of patients under Universal
      Coverage Scheme. CONCLUSIONS: Health care costs of patients with asthma were
      substantial and were higher in patients with high severe asthma and patients
      under the CSMBS.

PMID- 27881253
TI  - Erratum.

PMID- 27881254
TI  - Health Technology Assessment, International Reference Pricing, and Budget Control
      Tools from China's Perspective: What Are the Current Developments and Future
      Considerations?
AB  - BACKGROUND: China is investing considerably in health care reforms to address
      issues in its health care system. An example is access to innovative drugs, which
      remains challenging because it is largely dependent on patient self-pay.
      Recognizing this, the government has invested considerably in its basic medical
      insurance. As health care expenditure increases, there are growing concerns on
      budget control. Several health policy tools have been discussed recently such as
      health technology assessment, international reference pricing, and hospital
      budget control tools, which can be viewed as addressing the affordability
      concerns of the government budget. China has also listed her health outcomes
      goals in "Healthy China 2020" initiative. OBJECTIVES: This article aimed to
      discuss the "fit-for-purpose" of these tools to address budget concerns and
      support China in reaching her health outcomes goals. METHODS: The findings are
      informed by a panel discussion at ISPOR Asia Pacific 2014, literature review, and
      authors' experience. This review looks at the current developments in China and
      the considerations and implications for using these tools by drawing experiences
      from countries where they are used. RESULTS: These tools are generally used in
      countries with advanced health care systems. China's health care spending is
      still below that of countries with advanced health care systems and below World
      Health Organization recommendation. CONCLUSIONS: China has not yet reached the
      "critical mass" necessary for the effective use of these tools. As China
      continues its health care reforms, increase in health care spending to balance
      the health needs of the population would be key.

PMID- 27881256
TI  - Cost-Effectiveness Analysis of the Self-Management Program for Thai Patients with
      Metabolic Syndrome.
AB  - BACKGROUND: Lifestyle modification programs are partly evaluated for their
      usefulness. OBJECTIVES: This study aimed to assess the cost-effectiveness and
      healthy lifestyle persistence of a self-management program (SMP) for patients
      with metabolic syndrome (MetS) in Thai health care settings. METHODS: A cost
      effectiveness analysis was performed on the basis of an intervention study of 90
      patients with MetS randomly allocated to the SMP and control groups. A Markov
      model with the Difference-in-Difference method was used to predict the lifetime
      costs from a societal perspective and quality-adjusted life-years (QALYs), of
      which 95% confidence intervals (CIs) were estimated by bootstrapping. The cost
      effectiveness analysis, along with healthy lifestyle persistence, was performed
      using the discount rate of 3% per annum. Parameter uncertainties were identified
      using one-way and probabilistic sensitivity analyses. RESULTS: The lifetime costs
      tended to decrease in both groups. The SMP could save lifetime costs (-2310 baht;
      95% CI -5960 to 1400) and gain QALYs (0.0098; 95% CI -0.0003 to 0.0190), compared
      with ordinary care. The probability of cost-effectiveness was 99.4% from the
      Monte-Carlo simulation, and the program was deemed cost-effective at dropout
      rates below 69% per year as determined by the threshold of 160,000 baht per QALY
      gained. The cost of macrovascular complications was the most influencing variable
      for the overall incremental cost-effectiveness ratio. CONCLUSIONS: The SMP
      provided by the health care settings is marginally cost-effective, and the
      persistence results support the implementation of the program to minimize the
      complications and economic burden of patients with MetS.

PMID- 27881255
TI  - Cost-Effectiveness Analysis of Ticagrelor and Prasugrel for the Treatment of
      Acute Coronary Syndrome.
AB  - BACKGROUND: In the management of Asian patients with acute coronary syndrome
      (ACS), the comparative cost-effectiveness of ticagrelor and prasugrel, referenced
      to generic clopidogrel, is unknown. OBJECTIVE: To assess the cost-effectiveness
      of ticagrelor and prasugrel as compared with generic clopidogrel in patients with
      ACS in Singapore. METHODS: A Markov model simulating a typical cohort of 62-year
      old patients with ACS was constructed from a patient's perspective over a
      lifetime horizon. Treatment effects and adverse events, including nonfatal
      myocardial infarction, major bleeding related to non-coronary artery bypass
      grafting, dyspnea, or death, were estimated from pivotal trials comparing
      clopidogrel with ticagrelor and prasugrel, respectively. Costs were estimated
      from a tertiary hospital with more than 1500 admissions for ACS per year.
      RESULTS: The incremental cost-effectiveness ratio (ICER) per life-year gained for
      ticagrelor was about three times more favorable than for prasugrel (Singapore
      dollar [SGD] 13,276 vs. SGD 38,809). The ICER per quality-adjusted life-year
      (QALY) for prasugrel and ticagrelor, however, was comparable at SGD 18,921 and
      SGD 18,647, respectively. Deterministic sensitivity analysis revealed that the
      ICER per QALY gained for prasugrel and ticagrelor was most sensitive to the
      hazard ratio of all-cause mortality and utility for dyspnea, respectively.
      Probabilistic sensitivity analysis demonstrated that compared with clopidogrel,
      the probabilities of prasugrel and ticagrelor being cost-effective are 87.1% and
      88.3% based on the willingness-to-pay value of SGD 65,000 (one time the gross
      domestic product per capita in Singapore). CONCLUSIONS: Ticagrelor is more cost
      effective than prasugrel in reducing all-cause mortality in patients with ACS.
      The cost-effectiveness of ticagrelor and prasugrel become similar, however, when
      accounting for the impact of dyspnea on QALY.

PMID- 27881257
TI  - Economic Burden of Osteoporotic Fracture of the Elderly in South Korea: A
      National Survey.
AB  - BACKGROUND: Osteoporotic fractures (OFs) in the elderly are common worldwide, and
      the predicted number of the aging population is increasing the burden of OF on
      health care systems. OBJECTIVES: To estimate the economic burden of OF in people
      older than 65 years in South Korea from a societal perspective. METHODS: National
      Health Insurance claim databases were used to analyze health care utilization and
      medical costs of OF in the Korean population (49 million). We identified medical
      claims records with a diagnosis of OF and estimated the costs from 2007 to 2011.
      RESULTS: From 2007 to 2011, there were 244,798 patients with at least one medical
      insurance claim related to OF. Most patients had a single fracture (80%), whereas
      20% of all patients had two or more. For fracture sites, vertebral fracture
      accounted for 75.6% of all fractures, followed by hip and wrist fractures. The
      societal cost of OF increased annually, from US $88.8 million in 2007 to US
      $149.3 million in 2011. Among the entire cost, the direct medical cost was US
      $134.9 million in 2011, which includes the cost of treatment (US $91.2 million)
      and long-term care (US $48.1 million). The direct nonmedical cost was US $9.9
      million in 2011. Costs associated with morbidity and mortality of OF were
      excluded. CONCLUSIONS: The economic burden associated with OF in elderly is
      expected to rise with the predicted increase in life expectancy and the number of
      elderly in South Korea. Therefore, effective management of the disease is
      necessary to reduce the growth in the economic burden of OF.

PMID- 27881258
TI  - Cost-Effectiveness Analysis of Tocilizumab in Comparison with Infliximab in
      Iranian Rheumatoid Arthritis Patients with Inadequate Response to tDMARDs: A
      Multistage Markov Model.
AB  - OBJECTIVES: To analyze the cost-effectiveness of two common treatment strategies
      in Iran, comparing infliximab plus methotrexate with tocilizumab plus
      methotrexate in patients with rheumatoid arthritis with inadequate response to
      traditional disease-modifying antirheumatic drugs. METHODS: A multistage Markov
      decision model was applied to assess the incremental cost-effectiveness ratio
      (ICER) of a tocilizumab-containing regimen versus an infliximab-containing
      regimen over a 5-year time period. In the case of no response, we assumed that
      patients switched to the next treatment (adalimumab, rituximab, or supportive
      care) in sequence for each strategy. We considered major cost items, such as
      direct medical costs and direct nonmedical costs, from a payer (patients and
      third-party payers) perspective. A deterministic sensitivity analysis was
      conducted to assess the robustness of the model results over the uncertainty of
      key parameters. RESULTS: In the base-case analysis, the ICER of the tocilizumab
      containing regimen was US $60,800 per quality-adjusted life-year as compared to
      the infliximab-containing regimen. In the sensitivity analysis, changes in the
      price of the drugs by generic substitution, in utility scores, and in discount
      rate did not change our overall conclusions. Among all inputs to the primary
      study and the sensitivity analyses, however, the price of tocilizumab had the
      most impact on the ICER. CONCLUSIONS: Although tocilizumab and methotrexate
      provide a larger gain in quality-adjusted life-years, their current price is
      quite high as compared with those of our other interventions. Therefore, a
      regimen containing tocilizumab is not cost-effective as compared with an
      infliximab-containing regimen for patients with rheumatoid arthritis in Iran.

PMID- 27881259
TI  - Lifestyle-Related Metabolic Disorders, Osteoporosis, and Fracture Risk in Asia: A
      Systematic Review.
AB  - BACKGROUND: The prevalence of both lifestyle-related metabolic disorders and
      osteoporosis is increasing in Asia. OBJECTIVES: To conduct a systematic review of
      the published literature to identify studies examining disorders of glucose and
      lipid metabolism (type 2 diabetes, hyperglycemia, hypercholesterolemia,
      hyperlipidemia, dyslipidemia, metabolic syndrome [MetS], and atherosclerosis) as
      risk factors for osteoporosis and fracture in Asian populations. Studies
      examining the relationship between metabolic disorders and bone mineral density
      (BMD) were also included. METHODS: EMBASE (including MEDLINE) and the Cochrane
      Library were searched. Studies conducted only within Asia, which reported
      multivariate analysis with a sample size of 200 or more subjects, were included.
      RESULTS: A total of 32 studies were included. All six studies examining diabetes
      and fracture found that subjects with diabetes had a significantly higher risk of
      fracture than did subjects without diabetes (risk estimate range 1.26-4.73). Two
      studies found that subjects with atherosclerosis had a significantly higher risk
      of fracture (risk estimate range 1.10-2.52). Studies consistently reported that
      MetS is likely associated with osteoporosis or decreased BMD in men but not
      women. No consistent association was found for diabetes and BMD, with studies
      reporting contrasting results. There was limited evidence investigating lipid
      metabolism and hyperglycemia and risk of fracture or bone loss in Asian
      populations. CONCLUSIONS: These findings suggest that diabetes is a risk factor
      for fracture in Asian populations. MetS may be associated with bone loss in Asian
      men and atherosclerosis associated with increased fractures; however, caution is
      needed interpreting these findings given limitations in study design.

PMID- 27881261
TI  - Registration and Reimbursement of New Cancer Medicines in Australia.

PMID- 27881260
TI  - The EQ-5D-5L is More Discriminative Than the EQ-5D-3L in Patients with Diabetes
      in Singapore.
AB  - OBJECTIVES: To compare the discriminative power of the five-level version of the
      EuroQol five-dimensional questionnaire (EQ-5D-5L [5L]) and its three-level
      version (EQ-5D-3L [3L]) in patients with diabetes in Singapore. METHODS: A
      consecutive sample of patients with type 2 diabetes mellitus (T2DM) self
      completed the two versions of the EQ-5D in the clinic. The 3L index score was
      calculated from the Singapore 3L value set, whereas the 5L index score was mapped
      from the 5L index score using an interim scoring. The discriminative power of the
      two EQ-5D indices was assessed in terms of their relative efficiency (RE) in
      differentiating patients with T2DM with and without one of eight clinical
      conditions. The efficiency of the two EQ-5D classification systems was evaluated
      using the Shannon's index (H') and in terms of ceiling effects. RESULTS: A total
      of 121 patients with T2DM provided data for this study. The 3L score was
      systematically higher than the 5L score for patients with T2DM with a condition
      and systematically lower for the patients without a condition, with the mean
      differences being 0.005 and -0.011, respectively. The 5L index score showed
      higher RE in seven of eight clinical conditions (mean RE 1.87). The 5L
      classification system had higher H' in all dimensions: mobility (1.17 vs. 0.70),
      self-care (0.57 vs. 0.41), usual activities (1.01 vs. 0.72), pain/discomfort
      (1.47 vs. 1.02), and anxiety/depression (1.36 vs. 1.10). The overall ceiling
      effects decreased from 47.9% (3L) to 38.8% (5L). CONCLUSIONS: The EQ-5D-5L is
      more discriminative than the EQ-5D-3L in patients with T2DM in Singapore,
      supporting the use of EQ-5D-5L in the population.

PMID- 27881262
TI  - Registration and Reimbursement of New Cancer Medicines in Australia-Response to
      Letter to the Editor by Michael Wonder.

PMID- 27881263
TI  - Utilities for Type 2 Diabetes Treatment-Related Attributes in a South Korean and
      Taiwanese Population.
AB  - OBJECTIVES: To elicit utilities associated with type 2 diabetes medication
      related attributes from South Korean and Taiwanese populations and to identify
      key drivers of preferences. METHODS: Data from 59 respondents from the general
      population in South Korea and Taiwan were analyzed. Respondents' preferences were
      elicited using a paper-based standard gamble questionnaire. Health states were
      designed to identify the utility or disutility of type 2 diabetes medication
      related attributes, including dose frequency, nausea/vomiting (hereafter referred
      to as nausea), and weight change. RESULTS: The mean utility for the basic health
      state (encompassing current body weight and no nausea) was 0.754 +/- 0.155 with
      weekly dose administration. Respondents showed a preference for weekly over daily
      administration (average increase in utility of 0.043 across all health states
      with weekly, vs. daily, administration). Nausea was associated with a decrease in
      utility (average decrease of -0.034 across all health states with, vs. without,
      nausea). Weight gain had little effect on utility (average decrease of 0.000 and
      0.001 across all health states with, vs. without, 3% and 5% gain, respectively),
      although weight loss was associated with a small increase in utility (average
      increase of 0.028 and 0.029 across all health states with, vs. without, 3% and 5%
      loss, respectively). CONCLUSIONS: Utilities associated with type 2 diabetes
      medication-related attributes were elicited from a general population sample from
      South Korea and Taiwan. Treatment-related attributes, in particular dose
      frequency and nausea, had a measurable effect on utility and should be considered
      when selecting treatment regimens for South Korean or Taiwanese patients with
      type 2 diabetes.

PMID- 27881265
TI  - Importance of Economic Evaluation in Health Care: An Indian Perspective.
AB  - Health economic studies provide information to decision makers for efficient use
      of available resources for maximizing health benefits. Economic evaluation is one
      part of health economics, and it is a tool for comparing costs and consequences
      of different interventions. Health technology assessment is a technique for
      economic evaluation that is well adapted by developed countries. The traditional
      classification of economic evaluation includes cost-minimization, cost
      effectiveness analysis, cost-utility analysis, and cost-benefit analysis. There
      has been uncertainty in the conduct of such economic evaluations in India, due to
      some hesitancy with respect to the adoption of their guidelines. The biggest
      challenge in this evolutionary method is lack of understanding of methods in
      current use by all those involved in the provision and purchasing of health care.
      In some countries, different methods of economic evaluation have been adopted for
      decision making, most commonly to address the question of public subsidies for
      the purchase of medicines. There is limited evidence on the impact of health
      insurance on the health and economic well-being of beneficiaries in developing
      countries. India is currently pursuing several strategies to improve health
      services for its population, including investing in government-provided services
      as well as purchasing services from public and private providers through various
      schemes. Prospects for future growth and development in this field are required
      in India because rapid health care inflation, increasing rates of chronic
      conditions, aging population, and increasing technology diffusion will require
      greater economic efficiency into health care systems.

PMID- 27881264
TI  - Quality of Life and Economic Burden of Respiratory Disease in Asia-Pacific-Asia
      Pacific Burden of Respiratory Diseases Study.
AB  - OBJECTIVES: Asia-Pacific Burden of Respiratory Diseases is a cross-sectional,
      observational study examining the burden of disease in adults with respiratory
      diseases across six countries. The aim of this study was to describe health care
      resource use (HCRU), work impairment, cost burden, and health-related quality of
      life (HRQOL) associated with respiratory disease in the Asia-Pacific. METHODS:
      Consecutive participants aged 18 years or older with a primary diagnosis of
      asthma, allergic rhinitis, chronic obstructive pulmonary disease, or
      rhinosinusitis were enrolled. Participants completed a survey detailing
      respiratory symptoms, HCRU, work productivity and activity impairment, and HRQOL.
      Locally sourced unit costs for each country were used in the calculation of total
      costs. RESULTS: The study enrolled 5250 patients. Overall, the mean annual cost
      for patients with a respiratory disease was US $4191 (SGD 8489) per patient. For
      patients who reported impairment at work, the mean annual cost was US $7315 (SGD
      10,244), with productivity loss being the highest cost component for all four
      diseases (US $6310 [SGD 9100]). On average, patients were impaired for one-third
      of their time at work and 5% of their work time missed because of respiratory
      disease, which resulted in a 36% reduction in productivity. Patients with a
      primary diagnosis of chronic obstructive pulmonary disease had the greatest
      impact on HRQOL. CONCLUSIONS: In the Asia-Pacific, respiratory diseases have a
      significant impact on HCRU and associated costs, along with work productivity.
      Timely and effective management of these diseases has the potential to reduce
      disease burden and health care costs and improve work productivity and HRQOL.

PMID- 27881266
TI  - Budget Impact Analysis of Peritoneal Dialysis versus Conventional In-Center
      Hemodialysis in Malaysia.
AB  - OBJECTIVES: To investigate the 5-year health care budget impact of variable
      distribution of adult patients treated with peritoneal dialysis (PD) and in
      center hemodialysis (ICHD) on government funding in Malaysia. METHODS: An Excel
      based budget impact model was constructed to assess dialysis-associated costs
      when changing dialysis modalities between PD and ICHD. The model incorporates the
      current modality distribution and accounts for Malaysian government dialysis
      payments and erythropoiesis-stimulating agent costs. Epidemiological data
      including dialysis prevalence, incidence, mortality, and transplant rates from
      the Malaysian renal registry reports were used to estimate the dialysis patient
      population for the next 5 years. The baseline scenario assumed a stable
      distribution of PD (8%) and ICHD (92%) over 5 years. Alternative scenarios
      included the prevalence of PD increasing by 2.5%, 5.0%, and 7.5% or decreasing 1%
      yearly over 5 years. All four scenarios were accompanied with commensurate
      changes in ICHD. RESULTS: Under the current best available cost information, an
      increase in the prevalent PD population from 8% in 2014 to 18%, 28%, or 38% in
      2018 is predicted to result in 5-year cumulative savings of Ringgit Malaysia (RM)
      7.98 million, RM15.96 million, and RM23.93 million, respectively, for the
      Malaysian government. If the prevalent PD population were to decrease from 8% in
      2014 to 4.0% by 2018, the total expenditure for dialysis treatments would
      increase by RM3.19 million over the next 5 years. CONCLUSIONS: Under the current
      cost information associated with PD and HD paid by the Malaysian government,
      increasing the proportion of patients on PD could potentially reduce dialysis
      associated costs in Malaysia.

PMID- 27881267
TI  - Cost-Utility Analysis of Human Papillomavirus Vaccination and Cervical Screening
      on Cervical Cancer Patient in Indonesia.
AB  - BACKGROUND: Although cervical cancer is a preventable disease, the clinical and
      economic burdens of cervical cancer are still substantial issues in Indonesia.
      OBJECTIVES: The main purpose of this study was to model the costs, clinical
      benefits, and cost-utility of both visual inspection with acetic acid (VIA)
      screening alone and human papillomavirus (HPV) vaccination in addition to VIA
      screening in Indonesia. METHODS: We developed a population-based Markov model,
      consisting of three health states (susceptible, cervical cancer, and death), to
      assess future costs, health effects, and the cost-utility of cervical cancer
      prevention strategies in Indonesia. We followed a cohort of 100,000 females 12 to
      100 years old and compared VIA screening alone with the addition of HPV
      vaccination on top of the screening to "no intervention." RESULTS: The
      implementation of VIA screening alone and in combination with HPV vaccination
      would reduce the cervical cancer incidence by 7.9% and 58.5%, corresponding to 25
      and 98 deaths avoided within the cohort of 100,000, respectively. We also
      estimated that HPV vaccination combined with VIA screening apparently yielded a
      lower incremental cost-effectiveness ratio at international dollar 1863/quality
      adjusted life-year (QALY), compared with VIA screening alone (I$3126/QALY). Both
      strategies could however be definitely labeled as very cost-effective
      interventions, based on a threshold suggested by the World Health Organization.
      The incremental cost-effectiveness ratio was sensitive to the discount rate,
      cervical cancer treatment costs, and quality of life as part of the QALY.
      CONCLUSIONS: The addition of HPV vaccination on top of VIA screening could be a
      cost-effective strategy in Indonesia even if relatively conservative assumptions
      are applied. This population-based model can be considered as an essential tool
      to inform decision makers on designing optimal strategies for cervical cancer
      prevention in Indonesia.

PMID- 27881268
TI  - Antithrombotic Therapy and Direct Medical Costs in Patients with Acute Coronary
      Syndrome in Shanghai, China.
AB  - BACKGROUND: Acute coronary syndrome (ACS) is a leading cause of morbidity and
      mortality worldwide. OBJECTIVES: To describe patient profile, treatment patterns,
      and disease burden for patients with ACS. METHODS: A retrospective descriptive
      cohort study was conducted. Data were obtained from electronic medical records
      from seven Shanghai medical centers. Patients with at least one primary diagnosis
      of ACS from 2006 to 2012 were included. Patient ACS-related antithrombotic
      medication use, laboratory tests, key comorbidities, health care utilization, and
      direct medical costs were examined. Log-linear regression was conducted to
      explore factors associated with total direct medical costs. RESULTS: The mean age
      for the 6601 patients included was 69.7 +/- 12.5 years, and most of the patients
      (73%) were men. Comorbidities included diabetes (18.2%), hypertension (21.2%),
      and hyperlipidemia (8.6%). Out of these, 6466 (98%) patients had been
      hospitalized for ACS with an average length of stay of 14.0 +/- 16.4 days per
      hospitalization. A total of 914 (13.8%) patients had emergency room visits. Of
      these, 93.5% received any antithrombotic therapy, including antiplatelet agents
      (92.7%) and anticoagulants (20.8%). ACS-related direct medical costs (in yuan
      renminbi [Y]) were Y18,421 +/- Y24,741 per hospitalization, including costs for
      medications (Y6,776) and laboratory tests (Y1,355), and Y2,894 +/- Y7,060 per
      outpatient visit, including costs for medications (Y620) and laboratory tests
      (Y464). The higher direct medical cost was associated significantly (P < 0.05)
      with age, being male, antiplatelet and anticoagulant use, and several comorbid
      disease states (diabetes, hyperlipidemia, hypertension, and chronic kidney
      disease). CONCLUSIONS: Antithrombotic therapeutic treatments were commonly used
      among patients with ACS in Shanghai, China. Higher treatment costs for patients
      with ACS in Shanghai, China, involved their antithrombotic medication use and key
      comorbidities.

PMID- 27881269
TI  - Value of Information in Asia: Concepts, Current Use, and Future Directions.
AB  - Health technology assessment is a form of health policy research that provides
      policymakers with information relevant to decisions about policy alternatives.
      Findings from cost-effectiveness analysis (CEA) are one of the important aspects
      of health technology assessment. Nevertheless, the more advanced method of value
      of information (VOI), which is recommended by the International Society for
      Pharmacoeconomics and Outcomes Research and Society for Medical Decision Making
      Modeling Good Research Practices Task Force, has rarely been applied in CEA
      studies in Asia. The lack of VOI in Asian CEA studies may be due to limited
      understanding of VOI methods and what VOI can and cannot help policy decision
      makers accomplish. This concept article offers audiences a practical primer in
      understanding the calculation, presentation, and policy implications of VOI. In
      addition, it provides a rapid survey of health technology assessment guidelines
      and literature related to VOI in Asia and discusses the future directions of VOI
      use in Asia and its potential barriers. This article will enable health
      economists, outcomes researchers, and policymakers in Asia to better understand
      the importance of VOI analysis and its implications, leading to the appropriate
      use of VOI in Asia.

PMID- 27881271
TI  - Cost-Effectiveness Analysis Expands its Reach Worldwide.

PMID- 27881270
TI  - Cost-Effectiveness of Screening and Treatment for Cervical Cancer in Tanzania:
      Implications for other Sub-Saharan African Countries.
AB  - OBJECTIVES: To compare the institutional cost per person of screening and
      treatment between two groups of patients-those screened and those not screened
      before treatment for cervical cancer at Ocean Road Cancer Institute (ORCI) in Dar
      es Salaam, Tanzania-and to perform a cost-effectiveness analysis of the ORCI
      cervical cancer screening program. METHODS: The study included 721 screened and
      333 unscreened patients treated at ORCI for cervical cancer from 2002 to 2011. We
      compared the cost of cervical cancer treatment per patient with life-years gained
      for patients screened at ORCI versus not screened. RESULTS: Patients with cancer
      were diagnosed at an earlier stage after participating in screening compared with
      nonparticipants. For example, 14.0% of stage I cancer patients had received
      screening by ORCI compared with 7.8% of unscreened cases. For stage IV cancer,
      these percentages were 1.4% and 6.9%, respectively. Average screening and
      treatment cost for patients receiving cancer screening ($2526) was higher than
      that for unscreened patients ($2482). However, we calculated an incremental cost
      effectiveness ratio of $219 per life-year gained from receiving cervical cancer
      screening compared with not being screened, and thus the ORCI screening program
      was highly cost-effective. Furthermore, the screening program was associated with
      averting 1.3 deaths from cervical cancer each year resulting from earlier
      diagnoses of cancer cases, with the incremental cost-effectiveness ratio of $4597
      per life saved. CONCLUSIONS: Although Sub-Saharan Africa faces substantial
      challenges in population health management, our study highlights the potential
      benefits from expanding access to regular cervical cancer screening for women in
      this region.

PMID- 27881272
TI  - The Impact of a Pricing Policy Change on Retail Prices of Medicines in Egypt.
AB  - OBJECTIVES: To describe the products with price changes and assess the impact of
      price changes on the products' price and affordability within the context of the
      Egyptian market. METHODS: A descriptive pre-post observational study was
      conducted. We selected March through June 2013 as the post-change observation
      period. A matching pre-change observation period, one year earlier, was selected
      to be consistent with potential seasonal variation in product use. RESULTS: It
      was found that 65.7% of the products with price changes were low-priced generic
      products. The overall average percent change in price was 24.7%. Before decree
      #499 implementation, the average affordability of the low-, medium-, and high
      priced products was 0.25 days' wage, 2 days' wage, and more than 100 days' wage,
      respectively. After the implementation, the cost increase for the low- and medium
      priced products was less than 0.1 days' wage, whereas the high-priced products'
      cost decreased by 11 days' wage. CONCLUSIONS: The policy change resulted in both
      price decreases and increases without substantive implications on affordability.

PMID- 27881273
TI  - The Effects of the New Methodology Application on the Method of Pricing of Drugs
      The Case of the Republic of Macedonia.
AB  - BACKGROUND: The introduction of a new methodology for the pricing of drugs by the
      Agency of Medicines of the Republic of Macedonia for the period 2012 to 2015
      resulted in a price reduction of 1386 drugs. OBJECTIVE: This pioneer study
      evaluated the effects of the price changes during this period of 4 years and the
      consequent effects on the sale quantities for the segmented Anatomical
      Therapeutic Chemical groups. METHODS: The drugs were grouped by the size of the
      reductions, by segmenting the drugs by generic names, and by the Anatomical
      Therapeutic Chemical classification, in which the quantities are grouped by
      generic names and the prices are calculated by average values for a period of 1
      year. RESULTS: Analysis of the relations between price changes and quantities
      sold showed that since the introduction of the new methodology the decrease in
      the prices pushed down the sales of the drugs. CONCLUSIONS: This article presents
      not only the market developments but also projects the tendencies, concluding
      clearly that focusing only on the price reduction of drugs and not on the
      implementation of the pharmacoeconomic studies is deviating the supply of drugs
      that are on the market and affecting their quality. The trends indicate that
      patients are using old-generation drugs, packaging forms that do not fully answer
      the market demand, and policies that significantly affect the suppliers. The
      presented analysis confirms that if the new methodology is only partially
      implemented and is not followed in full consideration of the pharmacoeconomic
      studies, negative consequences will also have an impact on regional
      pharmaceutical markets, which are benchmarking prices of drugs with the
      Macedonian market.

PMID- 27881274
TI  - Performance Assessment of the Juaboso District Office of the National Health
      Insurance Authority.
AB  - OBJECTIVES: To assess the performance of the National Health Insurance Authority
      (NHIA) in Ghana. METHODS: Using a thorough case study of the Juaboso District
      Office of the NHIA, this study assessed the community coverage rate, the annual
      expenditure and income, and the trend of claims payment for the period 2009 to
      2012 as well as factors influencing the level of patronage of the National Health
      Insurance Scheme. A self-administered structured questionnaire was used to gather
      data from the management of the scheme. Secondary data were also gathered from
      the scheme's audited financial statements. Informal discussions were held with
      the premium collectors and clients to throw more light on revenue generation
      challenges. RESULTS: The study found an increasing trend in the coverage rate on
      a yearly basis. Over the study period, the rate moved from 30.6 to 60.1,
      representing an increase of 96.7%. This shows that in terms of coverage rate, the
      Juaboso District Office of the NHIA is performing very well. The study also found
      that revenue has increased but the percentage rate of increase has decreased,
      compared with the coverage percentage rate. Expenditure has been on the rise,
      increasing by as much as 20.7% in 2011. Again, the study revealed a consistent
      year-on-year increase in the claims payment, consistent with the national trend.
      CONCLUSIONS: Constant clinical auditing of claims payments is required to ensure
      accountability. This would lead to transparency with regard to performance
      assessment of the claims. The findings have important implications for the
      effective management of the NHIA.

PMID- 27881276
TI  - The Development of the Romanian Scorecard HTA System.
AB  - OBJECTIVES: To present the characteristics of the scorecard health technology
      assessment (HTA) implemented since 2014 and to show the results of this HTA
      process by the end of 2015. METHODS: The health care context and the Romanian HTA
      legislation were studied while considering the reasons behind HTA introduction,
      the key stakeholders, and the HTA process as a whole. A critical appraisal was
      done covering public HTA reports and the decisions made by the Ministry of
      Health. RESULTS: The scorecard HTA model is in place from 2014 and is based on
      six criteria: France HTA decision, UK HTA decision, Germany HTA decision, the
      number of European Union countries with reimbursement, the development of a local
      real-world data study, and a budget impact assessment. By December 2015, more
      than 200 HTA dossiers were evaluated and the scorecard HTA results were reflected
      in three processes of the drug reimbursement list update. Consequently, 25 new
      drugs, 11 fixed-dose combinations, 2 new indications, and 4 orphan drugs received
      unconditional inclusion, and 5 drugs received conditional inclusion via
      commercial arrangements. Moreover, the scorecard system was used for delisting
      drugs: 16 were delisted and another 21 were moved to a lower level of
      reimbursement (20%). CONCLUSIONS: The implementation of the scorecard HTA started
      in 2014 using combined information from Romania and other countries. Although the
      scorecard HTA system makes no direct evaluation of the value of drugs,
      authorities consider it to be effective, being designed only to favor cost-saving
      drugs and to promote high discounts.

PMID- 27881275
TI  - The Living with Medicines Questionnaire: Translation and Cultural Adaptation into
      the Arabic Context.
AB  - BACKGROUND: The Living with Medicines Questionnaire (LMQ) was developed in
      English language to assess, from a patient's perspective, issues related to the
      burden resulting from the use of medicines. OBJECTIVES: To translate and
      culturally adapt the LMQ into the Arabic language and context. METHODS:
      Permission to translate the LMQ was obtained from the original developers, and a
      protocol for its translation and cultural adaptation was developed using the
      International Society for Pharmacoeconomics and Outcomes Research guidelines for
      the translation and cultural adaptation of patient-reported outcome measures. Two
      forward translations (from English into Arabic) were developed and compared to
      produce the first reconciled version, which was back-translated into English. The
      resulting English version was compared with the original questionnaire leading to
      the second reconciled version. The emerged Arabic questionnaire was then
      cognitively tested among purposively selected individuals to assess the
      linguistic and cultural equivalence, and produce the final Arabic version.
      RESULTS: Issues identified and related to cultural and conceptual equivalence of
      some terms were resolved by rewording some items in the tool. The translation
      process and cognitive debriefing exercise generated comments regarding the
      original tool's construct and its Arabic equivalent, which were communicated to
      the developers of the LMQ for their consideration while conducting further
      comparative studies. CONCLUSIONS: A culturally suitable translation of the LMQ
      was generated for potential use in research and clinical practice in Arabic
      speaking countries. Further validation of the developed Arabic version is
      recommended and planned.

PMID- 27881277
TI  - Impact of Health Policy Changes on Trends in the Pharmaceutical Market in Turkey.
AB  - BACKGROUND: The implementation phase of the Turkish Health Transformation Program
      (HTP) began in 2003, with the aim of organizing, financing, and delivering health
      care services effectively, efficiently, and equally. The HTP impacted all
      clinical and economic outcomes of health, including pharmaceutical sales, by
      improving access to health services. OBJECTIVES: To understand the impact of five
      selected major policy changes that made an impact on supply, demand, or price in
      the pharmaceutical market between 1998 and 2012. METHODS: Monthly sales data (in
      units and value in US $) of a total of 180 pharmaceuticals covering the period
      between 1998 and 2012 were used for statistical analysis. Five major policies
      that could affect health expenditures and the demand and supply of
      pharmaceuticals were selected and led by the Ministry of Health. A P value of
      less than 0.05 was considered as the cutoff value for statistical significance.
      RESULTS: There was a growing trend in pharmaceuticals value and units in years,
      possibly as a result of the HTP implementation. Supply- and demand-related
      policies had a negative impact on the trends for value, whereas the pricing
      policy had a positive impact. CONCLUSIONS: It could be said that the HTP had an
      impact on units for improved access to health care services. Although this access
      increased the consumption of pharmaceuticals in units, the policies implemented
      were successful in controlling pharmaceutical expenditures.

PMID- 27881278
TI  - Cost Burden of Severe Community-Acquired Rotavirus Gastroenteritis Requiring
      Hospitalization in the Czech Republic, Slovakia, Poland, and Hungary: A
      Retrospective Patient Chart Review.
AB  - OBJECTIVES: To provide valuable local data on the economic burden of rotavirus
      gastroenteritis (RVGE) for decision making on introduction of rotavirus
      vaccination in Central European countries. METHODS: We conducted a retrospective
      patient hospital chart review during the winter RVGE peak in the Czech Republic
      (n = 109), Hungary (n = 109), Poland, (n = 112), and Slovakia (n = 115) to
      estimate resource use and associated costs from the payer's perspective in
      children younger than 5 years with severe RVGE requiring hospitalization.
      Microcosting analysis was used to estimate the average costs of treating RVGE
      inpatients including pre- and posthospitalization costs. RESULTS: The average
      cost of treatment was ?476, ?316, ?741, and ?594 in the Czech Republic, Hungary,
      Poland, and Slovakia, respectively. Extrapolating these costs to the total number
      of RVGE hospitalizations gives annual cost estimates of ?2.1 million, ?1.5
      million, ?13.2 million, and ?1.5 million, respectively. The main component of
      expenditure in all the four countries is the hospital stay, but wide variation
      among countries was observed (total cost of treating RVGE in hospital was almost
      2.5-fold higher in Poland than in Hungary). In countries with diagnosis related
      group (DRG) costs available, the best agreement between real resource-use-driven
      costs and the DRG cost was found in the Czech Republic and Hungary, with
      differences of only ?22 and ?33, respectively. In Poland, the microcosting
      indicated higher overall costs incurred in hospital than the DRG cost, with a
      difference exceeding ?190. CONCLUSIONS: Hospitalization of children with RVGE
      represents a substantial economic burden for the national health systems in these
      countries.

PMID- 27881279
TI  - The Economic Impact of Cigarette Smoking on the Poor in Jordan.
AB  - OBJECTIVES: To examine the expenditure on cigarette smoking in Jordan and compare
      the costs with potential investments in food and other essential items. METHODS:
      Review of available statistics and calculations were performed to estimate the
      economic cost of cigarette smoking in the Hashemite Kingdom of Jordan. Data on
      tobacco use and on household expenditures were collected from the Hashemite
      Kingdom of Jordan official databases. Information on the percentage of adult male
      smokers in each income group was based on cross-sectional data from 804 adult
      smokers. The average daily expenditure on cigarettes by cigarette smokers was
      based on a sample selected using a multistage, geographically clustered design.
      An example of a balanced diet was constructed on the basis of the recommendations
      of the jointly published dietary guidelines of the US Department of Health and
      Human Services and the US Department of Agriculture. RESULTS: Cigarette smoking
      prevalence is the highest among the poorest, with the highest rate (57%) being
      among adult males with an income of 100 to 250 Jordanian dinars per month as
      compared with the prevalence rate of 14% among adult males with an income of 500
      Jordanian dinars or more per month. Our calculations show that the poorest 40% of
      adult males are 1.7 times more likely to smoke cigarettes than the richest 17% of
      adult males. The average poorest adult male cigarette smoker with an income of
      100 to 250 Jordanian dinars per month spends approximately 25 times more on
      cigarettes than on health, approximately 10 times more on cigarettes than on
      education, approximately 2.5 times more on cigarettes than on housing, and
      approximately 1.5 times more on cigarettes than on food. The amount spent on
      cigarettes could potentially add up to 115 calories of a balanced diet per capita
      daily or 850 calories of a balanced diet per average cigarette smoker daily.
      Smoking cost the country 1 billion Jordanian dinars in 2012, including money
      spent on tobacco and smoking-related diseases, which amounted to approximately 5%
      of the gross domestic product. These calculations underestimate the real cost of
      smoking because these do not include the loss in work productivity due to
      smoking, which can be substantial. CONCLUSIONS: Our positive analysis shows that
      by adopting policies that reduce cigarette use, Jordan would be able to achieve
      both short- and long-run economic gains that will disproportionally benefit the
      poorest. Normative analysis suggests that an increase in tobacco taxes is likely
      to be the most efficient policy tool to reduce cigarette smoking in Jordan.

PMID- 27881280
TI  - Global Budget for Cyprus' National Health System: The Promised Land or a No Man's
      Land?
AB  - BACKGROUND: Soaring health expenditures worldwide call for potent cost
      containment approaches. Global budgets have been used by several countries to
      harness their health expenditures by constraining the total payable amount to a
      predefined budget threshold. OBJECTIVES: Cyprus is vacillating on the use of a
      global budget for its National Health System; nevertheless, its attributes must
      be scrutinized to rule out potential adverse effects on quality of care and
      access of patients. The delegation of budget across providers is a context
      sensitive process and as such it must be based on historical data and performance
      incentives as well. CONCLUSIONS: A global budget is not a panacea, and
      consequently the enhancement of health system's performance, appropriateness
      assessment, and volume and capacity control measures are incumbent. A global
      budget demonstrates a higher complexity factor for pharmaceuticals, which
      mandates a thorough assessment of pharmaceuticals before their reimbursement and
      elaboration of measures to safeguard timely access to innovation.

PMID- 27881281
TI  - Value and Service Quality Assessment of the National Health Insurance Scheme in
      Ghana: Evidence from Ashiedu Keteke District.
AB  - BACKGROUND: Ghana introduced the National Health Insurance Scheme (NHIS) in 2003
      to provide financial access to health care for all residents. OBJECTIVES: This
      article analyzed claims reimbursement data of the NHIS to assess the value of the
      benefit package to the insured and responsiveness of the service to the financial
      needs of health services providers. METHODS: Medical claims data reported between
      January 1, 2010, and December 31, 2014, were retrieved from the database of
      Ashiedu Keteke District Office of the National Health Insurance Authority. The
      incurred claims ratio, promptness of claims settlements, and claims adjustment
      rate were analyzed over the 5-year period. RESULTS: In all, 644,663 medical
      claims with a cost of Ghana cedi (GHS) 11.8 million (US $3.1 million) were
      reported over the study period. The ratio of claims cost to contributions paid
      increased from 4.3 to 7.2 over the 2011-2013 period, and dropped to 5.0 in 2014.
      The proportion of claims settled beyond 90 days also increased from 26% to 100%
      between 2011 and 2014. Generally, the amount of claims adjusted was low; however,
      it increased consistently from 1% to about 4% over the 2011-2014 period. The
      reasons for claims adjustments included provision of services to ineligible
      members, overbilling of services, and misapplication of diagnosis related groups.
      CONCLUSIONS: There is increased value of the NHIS benefit package to subscribers;
      however, the scheme's responsiveness to the financial needs of health services
      providers is low. This calls for a review of the NHIS policy to improve financial
      viability and service quality.

PMID- 27881283
TI  - Cost-Effectiveness of Introducing Point-of-Care Test for Detection of Level of
      Glycogen Phosphorylase in Early Diagnostic Algorithm of Acute Coronary Syndrome.
AB  - BACKGROUND: The detection of specific biomarkers in the early phase of acute
      coronary syndrome (ACS) is important for the early diagnosis and appropriate
      management of patients with ACS. OBJECTIVES: To estimate the cost-effectiveness
      of introducing a diagnostic point-of-care (POC) test for determining the levels
      of glycogen phosphorylase BB isoform (GPBB) in a standard diagnostic algorithm
      for the early diagnosis of ACS within the health system of the Republic of
      Serbia. METHODS: The probabilistic decision-tree model was constructed for
      patients with nontraumatic chest pain comparing the use of standard diagnostic
      procedure, physical examination, and electrocardiogram monitoring with the use of
      a diagnostic test for the detection of the levels of specific biomarkers. The
      perspective of the health care services purchaser (the Republic Institute for
      Health Insurance, Serbia) was used in the model, and only direct costs were taken
      into account. The time horizon was set at one treatment episode of ACS, and the
      discount rate was not included because of the short length of the time horizon.
      RESULTS: Using the GPBB POC test in comparison with not using it in the early
      diagnosis of ACS results in a significant reduction in the cost per treatment
      episode (10,034.48 +/- 7,283.80 Serbian dinar [RSD]), increase in the number of
      survivors per 1000 treatment episodes (16 +/- 18), decrease in the number of
      hospitalizations per 1000 treatment episodes (104 +/- 44), and decrease in the
      number of performed coronarographies per 1000 treatment episodes (22 +/- 19). The
      costs per hospitalization avoided (incremental cost-effectiveness ratio) were 
      145,887.57 +/- 5,271.54 RSD, and the costs per coronarography avoided were 
      137,295.68 +/- 4,681.05 RSD. CONCLUSIONS: In the circumstances of limited health
      resources, reducing hospitalizations and decreasing unnecessary treatments and
      invasive diagnostic procedures by a GPBB POC test could be an effective way to
      improve the economic status of other Balkan countries with limited health care
      budgets.

PMID- 27881282
TI  - Measuring and Valuing Informal Care for Economic Evaluation of HIV/AIDS
      Interventions: Methods and Application in Malawi.
AB  - BACKGROUND: Economic evaluation studies often neglect the impact of disease and
      ill health on the social network of people living with HIV (PLHIV) and the wider
      community. An important concern relates to informal care requirements which, for
      some diseases such as HIV/AIDS, can be substantial. OBJECTIVES: To measure and
      value informal care provided to PLHIV in Malawi. METHODS: A modified diary that
      divided a day into natural calendar changes was used to measure informal care
      time. The monetary valuation was undertaken by using four approaches: opportunity
      cost (official minimum wage used to value caregiving time), modified opportunity
      cost (caregiver's reservation wage), willingness to pay (amount of money
      caregiver would pay for care), and willingness to accept (amount of money
      caregiver would accept for providing care to someone else) approaches. Data were
      collected from 130 caregivers of PLHIV who were accessing antiretroviral therapy
      from six facilities in Phalombe district in southeast Malawi. RESULTS: Of the 130
      caregivers, 62 (48%) provided informal care in the survey week. On average,
      caregivers provided care of 8 h/wk. The estimated monetary values of informal
      care provided per week were US $1.40 (opportunity cost), US $2.41 (modified
      opportunity cost), US $0.40 (willingness to pay), and US $2.07 (willingness to
      accept). CONCLUSIONS: Exclusion of informal care commitments may be a notable
      limitation of many applied economic evaluations. This work demonstrates that
      inclusion of informal care in economic evaluations in a low-income context is
      feasible.

PMID- 27881284
TI  - Perceived Risks Contra Benefits of Using Biosimilar Drugs in Ulcerative Colitis:
      Discrete Choice Experiment among Gastroenterologists.
AB  - BACKGROUND: In middle-income countries, access to biological therapy is limited
      in ulcerative colitis in terms of the number of patients and the length of
      therapy. Because of their cost advantages, biosimilars have the potential to
      improve access to therapy, but physicians have concerns toward their use because
      of the lack of evidence from randomized clinical trials. OBJECTIVES: To explore
      the preferences of gastroenterologists for biosimilar drugs in ulcerative colitis
      as well as to compare our results with results of previous studies on
      gastroenterologists' preferences toward biosimilars. METHODS: A discrete choice
      experiment was carried out involving 51 Hungarian gastroenterologists treating
      patients with inflammatory bowel disease in May 2014 with the following
      attributes: type of treatment (biosimilar/originator), severity of disease,
      availability of continuous medicine supply, and the stopping rule (whether the
      treatment is covered after 12 months). A conditional logit model was used to
      estimate the probabilities of choosing a given profile. RESULTS: According to the
      results, the stopping rule was the most important attribute. The type of
      treatment mattered only for patients already on biologicals. The probabilities of
      choosing the biosimilar option with all the benefits offered in the discrete
      choice experiment over the originator option under the present reimbursement
      conditions are 85% for new patients and 63% for patients already treated.
      CONCLUSIONS: Most gastroenterologists have concerns about using biosimilars.
      They, however, are willing to consider the use of biosimilars if they could
      reallocate the potential savings to provide their patients better access to
      biological treatment.

PMID- 27881285
TI  - Conventionally Fractionationed Volumetric Arc Therapy versus Hypofractionated
      Stereotactic Body Radiotherapy: Quality of Life, Side Effects, and Prostate
      Specific Antigen Kinetics in Localized Prostate Cancer.
AB  - OBJECTIVES: To compare conventionally fractionationed volumetric arc therapy
      (VMAT) and hypofractionated stereotactic body radiotherapy (SBRT) modalities in
      terms of prostate-specific antigen (PSA) kinetics, toxicity, and quality of life
      (QOL) in patients with localized prostate cancer. METHODS: Patients received
      radical radiotherapy as either 33.5 Gy/5 fr for SBRT or 75.6 Gy/35 fr for VMAT.
      International Prostate Symptom Score (IPSS) and European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer
      Module (QLQ-PR25) forms were used to assess QOL. RESULTS: Of the 48 patients (28
      in SBRT and 20 in VMAT) included in the study, 40 (20 in SBRT and 20 in VMAT)
      were evaluated for QOL status. PSA control rate was 100% and PSA nadir value was
      0.5 ng/dl in both arms during the median follow-up period of 23 months. The
      magnitude of PSA bounce was higher in the SBRT arm than in the VMAT arm (P =
      0.01). The PSA decline rate in the VMAT arm was higher than in the SBRT arm (P =
      0.028). Three (10.7%) patients treated with SBRT who had a history of
      transurethral resection of the prostate (TURP) experienced grade 3 urinary
      toxicity. No significant difference was observed concerning sexual activity and
      sexual functioning scores, whereas scores at 10.5 and 13.5 months were decreased
      in both arms. The SBRT and VMAT arms had similar urinary incontinence, bowel
      symptoms, and IPSS obstruction scores. The magnitude of increase in IPSS scores
      at treatment completion was higher in the VMAT arm than in the SBRT arm (P =
      0.046). The decrease in hormonal symptom scores at 4.5, 10.5, and 13.5 months was
      higher in the VMAT arm than in the SBRT arm (P = 0.007, 0.027, and 0.021,
      respectively). CONCLUSIONS: Both treatment modalities had similar effectiveness
      and provided acceptable outcomes in terms of toxicity and QOL. Grade 3 urinary
      toxicities might be eliminated with careful patient selection for SBRT.

PMID- 27881286
TI  - Renal adaptive changes and sodium handling in the fetal-to-newborn transition.
AB  - Appropriate fluid and electrolyte management is critical for optimal care of very
      low birth weight or sick infants. Delivery of such care requires an understanding
      of developmental changes in renal water and salt handling that occur with
      advancing gestational age as well as postnatal age. This review focuses on the
      principles of sodium homeostasis during fetal and postnatal life. The physiology
      of renal tubular transport mechanisms, as well as neurohumoral factors impacting
      renal tubular transport are highlighted. Clinical implications and guidelines to
      the provision of sodium to this vulnerable population are also discussed.

PMID- 27881287
TI  - Obesity with Comorbid Stress Urinary Incontinence in Women: A Narrative Review to
      Inform Dietetics Practice.
AB  - Stress urinary incontinence (SUI) is a common problem among women; clinical
      treatment guidelines include weight reduction as a strategy for controlling
      urinary leakage. The purpose of this review was to gather evidence on the
      association between obesity and SUI and to ascertain whether there are any
      special considerations for implementing medical nutrition therapy with community
      dwelling, obese, adult females with comorbid SUI. Five key findings emerged:
      epidemiologic studies consistently report statistically significant associations
      between obesity and SUI, randomized control trials found that weight loss appears
      to ameliorate SUI symptoms, the SUI-activity link may affect weight management,
      there is a potential interplay between SUI and the obesity-sleep connection, and
      dietary components are associated with the exacerbation of urinary symptoms. The
      pathogenesis of SUI and obesity-related contributions to urinary leakage is
      included in the introductory discussion. Lastly, insights on special
      considerations for implementing nutrition interventions with this population are
      offered.

PMID- 27881288
TI  - Internal anal sphincter: Clinical perspective.
AB  - OBJECTIVE: To summarise current knowledge of Internal anal sphincter. BACKGROUND:
      The internal anal sphincter (IAS) is the involuntary ring of smooth muscle in the
      anal canal and is the major contributor to the resting pressure in the anus.
      Structural injury or functional weakness of the muscle results in passive
      incontinence of faeces and flatus. With advent of new assessment and treatment
      modalities IAS has become an important topic for surgeons. This review was
      undertaken to summarise our current knowledge of internal anal sphincter and
      highlight the areas that need further research. METHOD: The PubMed database was
      used to identify relevant studies relating to internal anal sphincter. RESULTS:
      The available evidence has been summarised and advantages and limitations
      highlighted for the different diagnostic and therapeutic techniques. CONCLUSION:
      Our understanding of the physiology and pharmacology of IAS has increased greatly
      in the last three decades. Additionally, there has been a rise in diagnostic and
      therapeutic techniques specifically targeting the IAS. Although these are
      promising, future research is required before these can be incorporated into the
      management algorithm.

PMID- 27881289
TI  - A comparative study of the endoscopy-assisted transoral approach versus external
      approaches for the resection of large benign parapharyngeal space tumors.
AB  - OBJECTIVE: The advantages and limitations of the endoscopy-assisted transoral
      approach (EATA) and external approaches (EAs) in resection of parapharyngeal
      space tumors (PSTs) remain unclear. In our study, we compared the use of the EATA
      and the EAs for the resection of large, benign PSTs. STUDY DESIGN: Forty-four
      patients with PSTs were divided into the EATA and EA groups. The perioperative
      and postoperative outcomes of the patients were evaluated. RESULTS: All of the
      tumors were completely removed. However, the procedure was converted to an open
      procedure for four patients in the EATA group and for six patients in the EA
      group who required endoscopic assistance. The intraoperative blood loss, amount
      and duration of drainage, postoperative pain, total hospital stay, and cosmetic
      outcomes were superior in the EATA group (P < .05). CONCLUSIONS: Use of the EATA
      for resection of large, benign PSTs decreased the surgical invasiveness of the
      procedure and resulted in better aesthetic outcomes. However, use of the combined
      surgical approach allowed for improved access for the resection of PSTs.

PMID- 27881290
TI  - Mercury, eicosapentanoic acid and docosahexaenoic acid demonstrate limited effect
      on plasma paraoxonase-1 activity and blood pressure among avid seafood consumers
      in the Long Island Study of Seafood Consumption, NY, USA.
AB  - BACKGROUND AND AIM: Moderate fish consumption is recommended for prevention of
      coronary heart disease (CHD) as docosahexaenoic acid (DHA) and eicosapentaenoic
      acid (EPA) have known beneficial effects on risk factors such as reducing blood
      pressure (BP) and increasing paraoxonase-1 (PON-1) activity. However concomitant
      methylmercury (MeHg) exposure from fish consumption may mitigate these benefits
      and the net effect on BP and PON-1 activity has not been extensively studied in
      western populations consuming diverse seafood types. We studied the correlation
      between EPA, DHA and Hg levels with BP and PON-1 activity in a population of avid
      seafood consumers. METHODS: Two hundred and eighty-eight avid seafood consumers
      from Long Island, NY had blood samples drawn for total blood mercury (THg),
      plasma EPA and DHA levels, and plasma PON-1 activity. Average systolic blood
      pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were
      measured. RESULTS: Subjects' mean EPA+DHA was 4.9% total fatty acids, mean THg
      was 7.6mcg/L. Mean SBP was 122.5mmHg, mean DBP 70.3mmHg, mean PP 52.2mmHg and
      mean PON-1 activity 421.2U/L. THg was not associated with any of the BP measures
      in adjusted linear regression models; EPA+DHA was significantly inversely
      associated with PP (p=0.02). THg was associated with a significant increase in
      PON-1 activity (p=0.04), while EPA+DHA was associated with a significant decrease
      in PON-1 activity (p=0.007); although the size of the effects was small.
      CONCLUSIONS: Our findings suggest blood THg and serum DHA+EPA levels have limited
      relationship to BP and PON-1 activity, and may not be important modulators of
      these known CHD risk factors in this population of avid seafood consumers.

PMID- 27881291
TI  - Assessment of Carotid Plaque Inflammation in Diabetic and Nondiabetic Patients-An
      Exploratory Ultrasmall Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance
      Imaging Study.
AB  - BACKGROUND: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic
      resonance (MR) imaging enables the identification of inflammation within the
      atheroma, predominantly by USPIO uptake by macrophages present in atherosclerotic
      tissue. Diabetic patients, however, may have dysfunctional macrophage activity,
      which may affect utilization of USPIO in identifying plaque inflammation in this
      patient cohort. METHODS: Fifteen diabetic and fifteen nondiabetic patients
      underwent USPIO-enhanced carotid MR imaging using 1.5T MR system. Pre- and post
      USPIO carotid MR images were manually coregistered. The percentage decrease in
      the signal intensity after USPIO administration was calculated as a relative
      measure of the USPIO uptake. RESULTS: Diabetic and nondiabetic patients had
      comparable demographics and comorbidities. The mean global, maximum quadrant, and
      maximum slice changes showing change in relative signal intensity as a result of
      USPIO administration were comparable for the two patient cohorts (P > .05).
      CONCLUSIONS: USPIO can identify inflammatory burden with carotid atheroma in both
      diabetic and nondiabetic patients.

PMID- 27881293
TI  - Onset of psoriatic arthritis associated with multiple wasp stings.

PMID- 27881294
TI  - Comparison of outcomes with arthroscopic repair of acute-on-chronic within 6
      months and chronic rotator cuff tears.
AB  - BACKGROUND: The purpose of this study was to define preoperative and
      intraoperative findings of acute-on-chronic rotator cuff tears (RCTs). This study
      also compared the functional and clinical outcomes with acute-on-chronic RCTs and
      chronic RCTs. METHODS: This study was conducted between December 2007 and
      December 2013. An acute-on-chronic full-thickness RCT was diagnosed with
      preoperative and intraoperative findings on arthroscopy. The study group
      consisted of 36 patients with preoperative and intraoperative findings (surgery
      performed within 6 months of trauma) indicative of an acute-on-chronic RCT.
      Another 36 patients matched for age, sex, and tear size, who underwent
      arthroscopic rotator cuff repair after 6 months of onset of symptoms (chronic RCT
      group), were selected from our institution's database within the same time frame.
      Postoperative indirect magnetic resonance arthrogram was obtained 6 months after
      the repair, and rotator cuff integrity was graded according to the guidelines as
      described by Sugaya. Patients were evaluated using the visual analog scale for
      pain, American Shoulder and Elbow Surgeons Shoulder Assessment score, and
      Constant scores. Scores and measurements were obtained preoperatively and at 6,
      12, and 24 months after surgery. RESULTS: The clinical outcomes and range of
      motion recovery were better in the acute-on-chronic RCT group. Although
      statistically not significant, the acute-on-chronic RCT group's repair appeared
      closer to the complete repair and was associated with a lesser incidence of
      retear than the chronic RCT group. CONCLUSION: Early repair of an acute-on
      chronic full-thickness RCT results in a statistically and clinically superior
      improvement in outcomes compared with repairs of chronic RCTs.

PMID- 27881295
TI  - Measuring dose from radiotherapy treatments in the vicinity of a cardiac
      pacemaker.
AB  - This study investigated the dose absorbed by tissues surrounding artificial
      cardiac pacemakers during external beam radiotherapy procedures. The usefulness
      of out-of-field reference data, treatment planning systems, and skin dose
      measurements to estimate the dose in the vicinity of a pacemaker was also
      examined. Measurements were performed by installing a pacemaker onto an
      anthropomorphic phantom, and using radiochromic film and optically stimulated
      luminescence dosimeters to measure the dose in the vicinity of the device during
      the delivery of square fields and clinical treatment plans. It was found that the
      dose delivered in the vicinity of the cardiac device was unevenly distributed
      both laterally and anteroposteriorly. As the device was moved distally from the
      square field, the dose dropped exponentially, in line with out-of-field reference
      data in the literature. Treatment planning systems were found to substantially
      underestimate the dose for volumetric modulated arc therapy, helical tomotherapy,
      and 3D conformal treatments. The skin dose was observed to be either greater or
      lesser than the dose received at the depth of the device, depending on the
      treatment site, and so care should be if skin dose measurements are to be used to
      estimate the dose to a pacemaker. Square field reference data may be used as an
      upper estimate of absorbed dose per monitor unit in the vicinity of a cardiac
      device for complex treatments involving multiple gantry angles.

PMID- 27881296
TI  - Is New-Onset Diabetes After Kidney Transplantation Associated with Autosomal
      Dominant Polycystic Kidney Disease in Recipients of Kidney Transplants?
      Incomplete Methodologies were Employed.

PMID- 27881292
TI  - Innate immunity, hemostasis and matrix remodeling: PTX3 as a link.
AB  - Innate immunity is evolutionarily connected with hemostasis. PTX3 is an essential
      fluid-phase pattern recognition molecule of the innate immune system that acts as
      a functional ancestor of antibodies. PTX3 by interacting with defense collagens
      and fibrinogens amplifies effector functions of the innate immune system. At
      wound sites, PTX3 regulates the injury-induced thrombotic response and promotes
      wound healing by favoring timely fibrinolysis. Therefore, PTX3 interacts with
      ancestral domains conserved in innate immunity, hemostasis and extracellular
      matrix and exerts functions related to both antimicrobial resistance and tissue
      repair. These findings strengthen the connection between innate immune system and
      hemostasis, and suggest that recognition of microbes and extracellular matrix are
      evolutionarily conserved and integrated functions of the innate immune system.

PMID- 27881298
TI  - Engaging Patients and Clinicians in Establishing Research Priorities for
      Gestational Diabetes Mellitus.
AB  - OBJECTIVES: We involved patients and clinicians in Alberta, Canada, to establish
      research priorities in gestational diabetes mellitus (GDM), using an approach
      based on a model proposed by the James Lind Alliance (JLA). METHODS: We adapted
      the 4-step JLA process to engage women with GDM and clinicians to identify
      uncertainties about the management of GDM. Uncertainties were identified through
      a survey and a review of the clinical practice guidelines (CPG). Uncertainties
      were short-listed by a steering committee, followed by a 1-day facilitated
      workshop using a nominal group format and involving a similar number of patients
      and clinicians, who identified the top 10 research priorities. RESULTS: Across
      the various survey formats, 75 individuals submitted 389 uncertainties, the
      majority (44; 59%) coming from patients. We removed 9 questions as being out of
      scope or unclear, and 41 were identified on a review of CPG, resulting in a total
      of 421 uncertainties. After the priority setting process, the final top 10
      research priorities included questions about a simpler, more accurate and
      convenient screening test; risk factors for GDM; improving postpartum diabetes
      screening; the impact of GDM on the future health of the children; lifestyle
      challenges and mental health issues; safety, effectiveness and/or impact of diet
      and/or medication treatments; appropriate timing for delivery; and how care is
      provided, organized or communicated. CONCLUSIONS: These top 10 research
      priorities were informed through a comprehensive and transparent process
      involving women who have experienced GDM as well as clinicians, and they may be
      regarded as research priorities for GDM.

PMID- 27881297
TI  - A Randomized Controlled Clinical Trial Investigating the Effects of Omega-3 Fatty
      Acids and Vitamin E Co-Supplementation on Biomarkers of Oxidative Stress,
      Inflammation and Pregnancy Outcomes in Gestational Diabetes.
AB  - OBJECTIVES: Limited data are available for assessing the effects of omega-3 fatty
      acids and vitamin E co-supplementation on metabolic profiles and pregnancy
      outcomes in gestational diabetes (GDM). This study was designed to determine the
      effects of omega-3 fatty acids and vitamin E co-supplementation on biomarkers of
      oxidative stress, inflammation and pregnancy outcomes in women with GDM. METHODS:
      This randomized, double-blind, placebo-controlled clinical trial was conducted in
      60 patients with GDM who were not taking oral hypoglycemic agents. Patients were
      randomly allocated to intake either 1000 mg omega-3 fatty acids from flaxseed oil
      plus 400 IU vitamin E supplements (n=30) or placebo (n=30) for 6 weeks. Fasting
      blood samples were obtained from the women at the beginning of the study and
      after the 6-week intervention to quantify related markers. RESULTS: After 6 weeks
      of intervention, omega-3 fatty acids and vitamin E co-supplementation, compared
      with the placebo, resulted in a significant rise in total antioxidant capacity
      (TAC) (+187.5+/-224.9 vs. -32.5+/-136.1 mmol/L; p<0.001); nitric oxide (NO)
      (+5.0+/-7.7 vs. -12.0+/-28.0 umol/L; p=0.002) and a significant decrease in
      plasma malondialdehyde (MDA) concentrations (-0.1+/-0.9 vs. +0.6+/-1.4 umol/L;
      p=0.03). Co-supplementation with omega-3 fatty acids and vitamin E showed no
      detectable changes in plasma glutathione and serum high-sensitivity C-reactive
      protein levels. Joint omega-3 fatty acids and vitamin E supplementation resulted
      in lower incidences of hyperbilirubinemia in newborns (10.3% vs. 33.3%; p=0.03).
      CONCLUSIONS: Overall, omega-3 fatty acids and vitamin E co-supplementation for 6
      weeks in women with GDM had beneficial effects on plasma TAC, MDA and NO and on
      the incidence of the newborns' hyperbilirubinemia.

PMID- 27881299
TI  - Transient RNA-DNA Hybrids Are Required for Efficient Double-Strand Break Repair.
AB  - RNA-DNA hybrids are a major internal cause of DNA damage within cells, and their
      degradation by RNase H enzymes is important for maintaining genomic stability.
      Here, we identified an unexpected role for RNA-DNA hybrids and RNase H enzymes in
      DNA repair. Using a site-specific DNA double-strand break (DSB) system in
      Schizosaccharomyces pombe, we showed that RNA-DNA hybrids form as part of the
      homologous-recombination (HR)-mediated DSB repair process and that RNase H
      enzymes are essential for their degradation and efficient completion of DNA
      repair. Deleting RNase H stabilizes RNA-DNA hybrids around DSB sites and strongly
      impairs recruitment of the ssDNA-binding RPA complex. In contrast, overexpressing
      RNase H1 destabilizes these hybrids, leading to excessive strand resection and
      RPA recruitment and to severe loss of repeat regions around DSBs. Our study
      challenges the existing model of HR-mediated DSB repair and reveals a surprising
      role for RNA-DNA hybrids in maintaining genomic stability.

PMID- 27881300
TI  - Structure of the MIND Complex Defines a Regulatory Focus for Yeast Kinetochore
      Assembly.
AB  - Kinetochores connect centromeric nucleosomes with mitotic-spindle microtubules
      through conserved, cross-interacting protein subassemblies. In budding yeast, the
      heterotetrameric MIND complex (Mtw1, Nnf1, Nsl1, Dsn1), ortholog of the metazoan
      Mis12 complex, joins the centromere-proximal components, Mif2 and COMA, with the
      principal microtubule-binding component, the Ndc80 complex (Ndc80C). We report
      the crystal structure of Kluyveromyces lactis MIND and examine its partner
      interactions, to understand the connection from a centromeric nucleosome to a
      much larger microtubule. MIND resembles an elongated, asymmetric Y; two globular
      heads project from a coiled-coil shaft. An N-terminal extension of Dsn1 from one
      head regulates interactions of the other head, blocking binding of Mif2 and COMA.
      Dsn1 phosphorylation by Ipl1/Aurora B relieves this autoinhibition, enabling MIND
      to join an assembling kinetochore. A C-terminal extension of Dsn1 recruits Ndc80C
      to the opposite end of the shaft. The structure and properties of MIND show how
      it integrates phospho-regulatory inputs for kinetochore assembly and disassembly.

PMID- 27881301
TI  - Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C
      at Human Kinetochores.
AB  - Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle
      microtubules to promote chromosome segregation. The 10-subunit KMN assembly
      (comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and
      NDC80C) binds microtubules and regulates mitotic checkpoint function through
      NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to
      the chromosome-proximal domain of the kinetochore through a direct interaction
      with CENP-C. The structural basis for this crucial bridging function of MIS12C is
      unknown. Here, we report crystal structures of human MIS12C associated with a
      fragment of CENP-C and unveil the role of Aurora B kinase in the regulation of
      this interaction. The structure of MIS12:CENP-C complements previously determined
      high-resolution structures of functional regions of NDC80C and KNL1C and allows
      us to build a near-complete structural model of the KMN assembly. Our work
      illuminates the structural organization of essential chromosome segregation
      machinery that is conserved in most eukaryotes.

PMID- 27881303
TI  - The Serotonergic System Tracks the Outcomes of Actions to Mediate Short-Term
      Motor Learning.
AB  - To execute accurate movements, animals must continuously adapt their behavior to
      changes in their bodies and environments. Animals can learn changes in the
      relationship between their locomotor commands and the resulting distance moved,
      then adjust command strength to achieve a desired travel distance. It is largely
      unknown which circuits implement this form of motor learning, or how. Using whole
      brain neuronal imaging and circuit manipulations in larval zebrafish, we
      discovered that the serotonergic dorsal raphe nucleus (DRN) mediates short-term
      locomotor learning. Serotonergic DRN neurons respond phasically to swim-induced
      visual motion, but little to motion that is not self-generated. During prolonged
      exposure to a given motosensory gain, persistent DRN activity emerges that stores
      the learned efficacy of motor commands and adapts future locomotor drive for tens
      of seconds. The DRN's ability to track the effectiveness of motor intent may
      constitute a computational building block for the broader functions of the
      serotonergic system. VIDEO ABSTRACT.

PMID- 27881302
TI  - Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol
      Binding Pocket.
AB  - Tetraspanins comprise a diverse family of four-pass transmembrane proteins that
      play critical roles in the immune, reproductive, genitourinary, and auditory
      systems. Despite their pervasive roles in human physiology, little is known about
      the structure of tetraspanins or the molecular mechanisms underlying their
      various functions. Here, we report the crystal structure of human CD81, a full
      length tetraspanin. The transmembrane segments of CD81 pack as two largely
      separated pairs of helices, capped by the large extracellular loop (EC2) at the
      outer membrane leaflet. The two pairs of helices converge at the inner leaflet to
      create an intramembrane pocket with additional electron density corresponding to
      a bound cholesterol molecule within the cavity. Molecular dynamics simulations
      identify an additional conformation in which EC2 separates substantially from the
      transmembrane domain. Cholesterol binding appears to modulate CD81 activity in
      cells, suggesting a potential mechanism for regulation of tetraspanin function.

PMID- 27881305
TI  - Technique for soft tissue closure in surgeries for fixed implant-supported
      prostheses in the edentulous maxilla.
AB  - A technique is presented that can be used as a straightforward, quick, and
      minimally invasive solution to improve soft tissue closure for surgeries
      involving bone reduction for fixed implant-supported prostheses in the edentulous
      maxilla.

PMID- 27881306
TI  - A modified method for fabricating a radiographic stent with transparent occlusal
      registration material for implant placement.

PMID- 27881307
TI  - Effect of polishing procedures and hydrothermal aging on wear characteristics and
      phase transformation of zirconium dioxide.
AB  - STATEMENT OF PROBLEM: Yttria-stabilized zirconia used for the fabrication of
      crowns and fixed prostheses may require intraoral adjustments after placement and
      cementation. Grinding and polishing methods may result in changes in the surface
      characteristics of zirconia. PURPOSE: The purpose of this in vitro study was to
      assess the effect of polishing procedures on surface roughness, topographical and
      phase changes of zirconia, and wear of the opposing dentition. MATERIAL AND
      METHODS: Presintered and precut yttria-stabilized zirconia specimens (10*10*1 mm)
      were divided into 4 groups (control, Intensiv, Shofu, 3M ESPE) depending on the
      polishing method used to prepare the specimens. All tests were carried out in
      triplicate. The specimens were polished depending on the polishing regimen, while
      the control was left untreated. The specimens were thermocycled for 3000 cycles,
      with a temperature range of 5 degrees C to 55 degrees C. The surface roughness,
      elemental, and phase changes caused by polishing before and after thermocycling
      were assessed with surface profilometry, energy-dispersive spectroscopy, and x
      ray diffraction analysis. The wear on antagonist steatite balls was also measured
      after mastication simulation. Statistical analysis was performed using 1-way
      ANOVA and the Tukey post hoc test to perform multiple comparison tests
      (alpha=.05). RESULTS: The polishing procedures increased surface roughness (Ra)
      of yttria-stabilized zirconia from 0.52 for the control specimen to 0.73 for
      Intensiv, 0.70 for Shofu, and 0.70 for 3M ESPE (P<.05), which was reduced by
      thermocycling to 0.44 (control), 0.58 (Intensiv), and 0.58 (Shofu) (P<.001),
      while roughness remained unchanged for 3M ESPE specimens (0.75; P=.452). The
      deposition of aluminum when using Shofu abrasives and nickel in Intensiv was
      demonstrated. Phase changes were observed on the zirconia surface with formation
      of the monoclinic phase in all polishing methods. Specimen aging enhanced the
      surface phase changes and also induced compressive stresses in zirconia polished
      with Intensiv. The different polishing protocols did not affect the wear to the
      antagonist (P>.05). CONCLUSIONS: Polishing zirconia increased surface roughness
      and led to surface phase changes, but wear to the antagonist was not affected.

PMID- 27881304
TI  - Mitochondrial Sirtuin Network Reveals Dynamic SIRT3-Dependent Deacetylation in
      Response to Membrane Depolarization.
AB  - Mitochondrial sirtuins, SIRT3-5, are NAD+-dependent deacylases and ADP
      ribosyltransferases that are critical for stress responses. However, a
      comprehensive understanding of sirtuin targets, regulation of sirtuin activity,
      and the relationships between sirtuins remains a key challenge in mitochondrial
      physiology. Here, we employ systematic interaction proteomics to elucidate the
      mitochondrial sirtuin protein interaction landscape. This work reveals sirtuin
      interactions with numerous functional modules within mitochondria, identifies
      candidate sirtuin substrates, and uncovers a fundamental role for sequestration
      of SIRT3 by ATP synthase in mitochondrial homeostasis. In healthy mitochondria, a
      pool of SIRT3 binds ATP synthase, but upon matrix pH reduction with concomitant
      loss of mitochondrial membrane potential, SIRT3 dissociates. This release
      correlates with rapid deacetylation of matrix proteins, and SIRT3 is required for
      recovery of membrane potential. In vitro reconstitution experiments, as well as
      analysis of CRISPR/Cas9-engineered cells, indicate that pH-dependent SIRT3
      release requires H135 in the ATP5O subunit of ATP synthase. Our SIRT3-5
      interaction network provides a framework for discovering novel biological
      functions regulated by mitochondrial sirtuins.

PMID- 27881309
TI  - Survey of dentists to determine contemporary use of endodontic posts.
AB  - STATEMENT OF PROBLEM: Although the scientific literature provides sound decision
      making tools for the restoration of endodontically treated teeth, dentists have
      different opinions on the rationale for the use of endodontic posts (dowels) and
      selection of post systems. The decision to place a post is at times contrary to
      the literature. Updated information on the treatment of endodontically treated
      teeth among general dentists is lacking. PURPOSE: The purpose of this survey was
      to gain insight into the rationale for choice of endodontic posts and the
      different endodontic post systems currently used by dental practitioners. Post
      and core restorations distribute stress and replace missing tooth structure in
      endodontically treated teeth. Guidelines exist to help select post systems. With
      the advent of new materials, prefabricated posts have gained popularity among
      dentists. However, cast-metal post-and-core systems are still considered the gold
      standard. MATERIAL AND METHODS: Surveys were distributed to dentists attending
      continuing education meetings in the United States, Canada, Scotland, Ireland,
      and Greece. The questions addressed years of practice, specialty training, and
      brand, type, shape, and material of the endodontic post systems used. RESULTS:
      Descriptive statistical analysis was used to assess the percentage of
      respondents. Ninety-two percent of the participants were general practitioners
      with 25.94 +/-13.35 years of experience. The majority agreed upon using
      endodontic posts when insufficient coronal tooth structure remains and for stress
      distribution. Passive, parallel posts were the most commonly reported type and
      shape. With regard to post material, fiber posts were the most frequently used
      (72.2%), followed by prefabricated alloys (38.6%), cast-metal posts (33.9%),
      prefabricated titanium posts (30.1%), and stainless-steel posts (21.7%). For
      cementation, resin-modified glass ionomer (40%) was most frequently used,
      followed by self-adhesive resin (29.6%). CONCLUSIONS: The majority of the
      practitioners used fiber posts. This may be because, in terms of fracture, they
      compare favorably with cast-metal post and core, although little evidence in the
      literature validates this claim.

PMID- 27881308
TI  - Technique for transferring the path of insertion of a removable partial denture
      to a CAD-CAM-generated implant surgical template.
AB  - A technique is described that uses a surveyor, gutta percha points, and a
      computer-aided design and computer-aided manufacturing (CAD-CAM)-guided implant
      surgery system to predetermine and transfer the ideal angulation of the implant
      to be placed.

PMID- 27881310
TI  - Implant-retained skull prosthesis to cover a large defect of the hairy skull
      resulting from treatment of a basal cell carcinoma: A clinical report.
AB  - Skin carcinoma, particularly basal cell carcinoma, and its treatment can result
      in large defects of the hairy skull. A 53-year-old man is described who was
      surgically treated for a large basal cell carcinoma invading the skin and
      underlying tissue at the top of the hairy skull. Treatment consisted of resecting
      the tumor and external part of the skull bone. To protect the brain and to cover
      the defect of the hairy skull, an acrylic resin skull prosthesis with hair was
      designed to mask the defect. The skull prosthesis was retained on 8 extraoral
      implants placed at the margins of the defect in the skull bone. The patient was
      satisfied with the treatment outcome.

PMID- 27881311
TI  - A photoelastic and strain gauge comparison of two attachments for obturator
      prostheses.
AB  - STATEMENT OF PROBLEM: The rehabilitation of patients after a maxillectomy
      involves the use of an obturator to seal oral-nasal-sinus communication and to
      facilitate mastication, swallowing, and speech. PURPOSE: The purpose of this in
      vitro study was to evaluate different attachment systems used for implant
      retained obturators at dissipation loads and under shear forces. MATERIAL AND
      METHODS: Photoelastic models were fabricated with 3 external hexagon implants at
      the incisor, canine, and first molar regions. Subsequently, overdentures were
      made, and metal hooks were placed at the incisor and first molar regions to
      displace the prostheses in the vertical, anterior, and posterior directions, with
      a constant speed of 50 mm/min. A photoelastic model with an O-ring or bar-clip
      system was placed in a circular polariscope, and tested with a universal testing
      machine. The images were recorded and high-intensity fringes were counted using
      software. For strain gauge analysis, each strain gauge was placed horizontally at
      the mesial and distal sides of the implants. The registered strains were
      submitted to 2-way ANOVA (alpha=.05). RESULTS: The O-ring showed the lowest
      number of high-intensity fringes in photoelastic imaging, while the strain gauge
      analysis showed the lowest stress values in the bar-clip group (P=.007).
      CONCLUSIONS: The stress around titanium implant necks was more damaging to
      surrounding bone, while the bar-clip attachment system had a better biomechanical
      performance. The bar-clip presented the lowest strain values around the dental
      implants and few high-intensity fringes.

PMID- 27881312
TI  - Detachable cheek plumpers with different attachments for improving esthetics in a
      conventional complete denture: A clinical report.
AB  - Aging is associated with loss of teeth, resorption of the alveolar process, and
      reduced tonicity of the facial muscles, leading to sunken cheeks and an
      unesthetic appearance. Esthetics in patients in need of complete dentures can be
      improved with the help of cheek plumpers to support the cheeks. They are
      noninvasive and straightforward to fabricate. Despite the reported success with
      the sole use of maxillary cheek plumpers, in certain situations, maxillary cheek
      plumpers provide inadequate support to the cheeks, evident in the lower third of
      the face. This clinical report describes a technique for fabricating detachable
      mandibular and maxillary cheek plumpers with 2 different types of attachment
      mechanisms.

PMID- 27881313
TI  - Effect of internal hexagonal index on removal torque and tensile removal force of
      different Morse taper connection abutments.
AB  - STATEMENT OF PROBLEM: The maintenance of the mechanical stability of implant
      abutment connections is relevant to the clinical success of implant-supported
      restorations. However, the reduction in the conical area of abutments with an
      internal hexagonal index may result in a biomechanical disadvantage in Morse
      taper connections. PURPOSE: The purpose of this in vitro study was to evaluate
      the influence of an internal hexagonal index on the removal torque and tensile
      removal force of different Morse taper connection abutments submitted to
      thermomechanical cycling. MATERIAL AND METHODS: Forty Morse taper implants with
      their respective abutments were divided into 4 groups (n=10): straight abutment
      without index (PRNI); straight abutment with index (PRI); angled abutment without
      index (PANI); and angled abutment with index (PAI). Each abutment received an
      insertion torque of 15 Ncm, and the removal torque was recorded before and after
      thermomechanical cycling (106 cycles, 2 Hz, load of 130 N). After cycling, the
      groups were submitted to tensile testing at 0.5 mm/min under a load of 500 N
      until displacement of the abutment. A paired t test was performed for the
      intragroup analysis of removal torque before and after cycling and 2-way ANOVA
      followed by the Tukey Honestly Significant Difference (HSD) test was used for
      intergroup comparison (alpha=.05). RESULTS: Statistical analysis showed
      significant differences in intragroup removal torque values before compared with
      after thermomechanical cycling (P<.05). No statistically significant differences
      were found between the experimental groups in the removal torque of the
      prosthetic screw after cycling. The index factor (P=.028) was significant for
      tensile removal force. CONCLUSIONS: The type of abutment did not significantly
      influence the removal torque or tensile removal force after cycling. However, the
      presence of the internal hexagonal index significantly reduced the force
      necessary to dislodge the abutment from the implant.

PMID- 27881314
TI  - Orientation of handle for successful prosthetic treatment in patients with an
      anatomic compromise after a maxillectomy.
AB  - This clinical technique provides a key procedure for successful prosthetic
      treatment in patients with an anatomical compromise after a maxillectomy. When
      making a preliminary impression, the clinician must keep the handle of the stock
      tray parallel to the patient's interpupillary line extraorally to maintain the
      correct position of the tray and to make a record of the inclination of the
      occlusal plane. This simple consideration during this first step of making a
      preliminary impression can be an important guide for both dentists and dental
      technicians. Information about the correct positioning of the tray and the
      inclination of the occlusal plane obtained by using a stock tray handle will
      greatly reduce the stress experienced by dentists, dental technicians, and
      patients during the fabrication of the prosthesis and will ultimately lead to
      successful prosthetic treatment in patients with anatomic compromise resulting
      from a maxillectomy.

PMID- 27881315
TI  - CAD-CAM implant-supported fixed complete dental prosthesis with titanium milled
      molars: A clinical report.
AB  - Implant-supported fixed complete dental prostheses have been associated with a
      high implant success rate in long-term studies. However, they have also been
      associated with a high frequency of prosthetic complications. The most frequent
      and primary prosthetic complication has been the fracture or wear of the occlusal
      surface of acrylic resin teeth that are typically attached to a metal framework.
      The design of the framework in this clinical report involved the incorporation of
      metal occlusal surfaces for the posterior first molars to the framework. The
      titanium framework was fabricated with computer-aided design and computer-aided
      manufacturing (CAD-CAM) technology. The remaining teeth were restored in a
      conventional manner with acrylic resin denture teeth bonded to the titanium
      framework. This was expected to maintain the occlusal vertical dimension and also
      reduce the frequency of the primary complications associated with these
      prostheses.

PMID- 27881316
TI  - Effects of aqueous and acid-based coloring liquids on the hardness of zirconia
      restorations.
AB  - STATEMENT OF PROBLEM: The effects of the application of aqueous coloring liquids
      on the mechanical properties of zirconia have not yet been investigated. PURPOSE:
      The purpose of this in vitro study was to evaluate the effects of 3 different
      coloring techniques and the number of coloring liquid applications on the
      hardness of zirconia. MATERIAL AND METHODS: Eighty specimens were divided into 8
      groups (n=10); nonshaded zirconia, preshaded zirconia, acid-based coloring liquid
      zirconia, and aqueous coloring liquid zirconia (1, 3, 6). Vickers hardness was
      measured. Data were analyzed via 1-way and 2-way ANOVAs. Multiple comparisons
      were performed using a Scheffe test (alpha=.05). RESULTS: Statistically
      significant differences in hardness were found between acid-based coloring liquid
      zirconia and aqueous coloring liquid zirconia (P<.001). Increasing the number of
      coloring liquid applications decreased the hardness value of acid-based coloring
      liquid zirconia (P<.001) but had no effect on the hardness of aqueous coloring
      liquid zirconia (P>.05). CONCLUSIONS: Within the limitations of this study, the
      hardness of zirconia was influenced to differing degrees depending on coloring
      technique. The number of coloring liquid applications affected the hardness of
      zirconia colored with the acid-based coloring liquid but not the hardness of
      zirconia colored with the aqueous coloring liquid.

PMID- 27881317
TI  - An update on computer-engineered complete dentures: A systematic review on
      clinical outcomes.
AB  - STATEMENT OF PROBLEM: Reports on computer-engineered complete dentures (CECDs)
      continue to increase. Systematic reviews on clinical outcomes and applications
      associated with CECDs are lacking in the literature. PURPOSE: The purpose of this
      systematic review was to determine the clinical outcomes and applications of
      CECDs. MATERIAL AND METHODS: Electronic searches of the English literature from
      January 1984 to May 2016 were performed in MEDLINE and Cochrane databases, with
      the results enriched by hand searches and citation mining to address 2 relevant
      population intervention comparison outcome (PICO) questions: What are the
      clinical outcomes associated with CECDs? Are there specific applications and
      significant advantages for CECDs? RESULTS: A review of the selected articles on
      CECDs revealed significantly better retention and reduced clinical time for the
      milled CECDs compared with conventional complete dentures. An advantage
      associated with CECDs is the possibility of electronically archiving data using
      digital technology for rapid fabrication. Applications reported in the literature
      with CECDs were also identified. CONCLUSIONS: A positive trend was seen in the
      outcomes with CECDs, although patient selection might have also contributed to
      favorable outcomes. Significantly reduced clinical time, improved retention, and
      digital archiving were the main advantages associated with CECDs.

PMID- 27881318
TI  - Clinical characteristics of an allergic reaction to a polyether dental impression
      material.
AB  - Allergic and hypersensitivity reactions to dental impression materials may occur
      throughout dental treatment, with diverse manifestations from slight redness to
      severe pain and a burning mouth with total stomatitis. Patients are often unaware
      of these allergic reactions, which makes early identification of the cause almost
      impossible. In addition, symptoms usually begin after 24 hours and mostly in
      patients with a preexisting history of allergic responses. This report describes
      a patient with a suspected allergic reaction to a polyether dental impression
      material during prosthetic rehabilitation associated with a mandibular telescopic
      denture. Although instances of such occurrence are rare, clinicians need to be
      aware of these symptoms and select materials carefully for patients with a
      history of allergy.

PMID- 27881319
TI  - Influence of remaining tooth structure and restorative material type on stress
      distribution in endodontically treated maxillary premolars: A finite element
      analysis.
AB  - STATEMENT OF PROBLEM: How tooth preparation and material type affect the stress
      distribution of endodontically treated teeth restored with endocrowns remains
      unclear. PURPOSE: The purpose of this finite element (FE) study was to determine
      the influence of the quantity of remaining dental tissues and material type on
      stress distribution in endodontically treated maxillary premolars using 3
      dimensional FE analysis. MATERIAL AND METHODS: Five 3-dimensional FE models were
      constructed on the basis of the restorative methods used and the quantity of
      preserved tooth tissues: a sound maxillary premolar, an endodontically treated
      maxillary premolar restored with composite resin, and endodontically treated
      maxillary premolars restored with endocrowns with thicknesses of 1.0 mm, 2.0 mm,
      and 3.0 mm. The following endocrown materials were used: Paradigm MZ100, IPS
      Empress, IPS e.max CAD, and In-Ceram Zirconia. Stress distributions were analyzed
      under vertical and oblique loads. RESULTS: As the quantity of preserved dental
      tissues increased, the von Mises stress in dentin decreased, and the peak von
      Mises strain value of the cement layer increased. When the elastic modulus of the
      endocrown material increased, the von Mises stress in endocrown and dentin
      increased, and the peak von Mises strain value of the cement layer decreased.
      CONCLUSIONS: Although the conservative preparation of teeth for endocrowns is
      likely to protect the residual tooth structure, it may cause future cohesive
      bonding failure. An increase in the elastic modulus of the material may benefit
      the durability of bonding between the endocrown and the abutment tooth; however,
      it may cause fracture of the residual tooth structure.

PMID- 27881320
TI  - Fabrication of an unconventional bolus-type stent for a combined
      intraoral/extraoral defect treated with proton radiation therapy.
AB  - Customized intraoral devices help the radiation oncologist minimize the adverse
      effects of radiation and maximize the tumor control rate by keeping the anatomic
      structures in a consistent position during each fraction of radiation treatment.
      This article illustrates the fabrication of a bolus-type positioning device for a
      combined intraoral/extraoral defect treated with proton radiation therapy.

PMID- 27881321
TI  - A digital approach integrating facial scanning in a CAD-CAM workflow for complete
      mouth implant-supported rehabilitation of patients with edentulism: A pilot
      clinical study.
AB  - STATEMENT OF PROBLEM: Complete-mouth implant-supported rehabilitations are
      challenging because of the multiple surgical and prosthetic steps involved in
      clinical evaluations to assure passive prosthesis fit and optimal esthetic and
      functional outcomes. As a result, these rehabilitations are usually associated
      with substantial clinical time, patient discomfort, and high treatment cost.
      PURPOSE: The purpose of this pilot clinical study was to evaluate a novel digital
      approach integrating digital intraoral dental and extraoral facial scanning
      information to design and mill a computer-aided design and computer-aided
      manufacturing (CAD-CAM) implant-retained prosthesis for patients with complete
      edentulism. MATERIAL AND METHODS: Ten patients in need of complete-mouth
      rehabilitation were included in this pilot study. Digital intraoral records were
      obtained through optical scanning the duplicate interim prosthesis using a
      laboratory scanner, while digital extraoral records were obtained through facial
      scanning using an in-office scanner. The scanned impressions and occlusal records
      were used to create a virtual tooth arrangement, which was matched to the
      patient's 3-dimensional face scan to create a virtual clinical evaluation phase.
      After applying the necessary adjustments, the virtual arrangement was submitted
      to a CAM procedure where a 5-axis industrial milling machine was used to
      fabricate an interim prosthesis. RESULTS: Digital intraoral and extraoral records
      were integrated and used to fabricate CAD-CAM milled interim prostheses, which
      were inserted and assessed for clinical fit, occlusion/articulation, and
      esthetics. The prostheses remained in function for at least 6 months with no
      notable technical or biological complications except for 1 prosthesis that
      fractured. CONCLUSIONS: A novel digital workflow incorporating facial scanning in
      a CAD-CAM workflow was used to fully digitally design and mill 10 implant
      retained interim prostheses. More research is required to further develop and
      assess the accuracy and applicability of this approach.

PMID- 27881322
TI  - Layperson's preference regarding orientation of the transverse occlusal plane and
      commissure line from the frontal perspective.
AB  - STATEMENT OF PROBLEM: Facial asymmetries in features such as lip commissure and
      interpupillary plane canting have been described as common conditions affecting
      smile esthetics. When presented with these asymmetries, the clinician must choose
      the reference line with which to orient the transverse occlusal plane of the
      planned dental restorations. PURPOSE: The purpose of the online survey described
      in this study was to determine lay preferences regarding the transverse occlusal
      plane orientation in faces that display a cant of the commissure line viewed from
      the frontal perspective. MATERIAL AND METHODS: From a digitally created
      symmetrical facial model with the transverse occlusal plane and commissure line
      parallel to the interpupillary line (horizontal) and a model constructed in a
      previous study (control), a new facial model was created with 3 degrees of cant
      of the commissure line. Three digital tooth mountings were designed with
      different transverse occlusal plane orientations: parallel to the interpupillary
      line (A), parallel to the commissure line (B), and the mean angulation plane
      formed between the interpupillary and commissure line (C), resulting in a total
      of 4 images. All images, including the control, were organized into 6 pairs and
      evaluated by 247 selected laypersons through an online Web site survey. Each
      participant was asked to choose the more attractive face from each of the 6 pairs
      of images. RESULTS: The control image was preferred by 72.9% to 74.5% of the
      participants compared with the other 3 images, all of which represented a
      commissure line cant. Among the 3 pairs which represent a commissure line cant,
      59.1% to 61.1% preferred a transverse plane of occlusion cant (B and C) compared
      with a plane of occlusion parallel to the interpupillary, line and 61.1%
      preferred a plane of occlusion parallel to the commissure line (B) compared with
      the mean angulation plane (C). CONCLUSIONS: Laypeople prefer faces with a
      commissure line and transverse occlusal plane parallel to the horizontal plane or
      horizon. When faces present a commissure line cant, laypeople prefer a transverse
      occlusal plane with a similar and coincident cant.

PMID- 27881323
TI  - Celebrity smile esthetics assessment: Smile angulation.
AB  - STATEMENT OF PROBLEM: Whether deviations in the angulation discrepancy between
      the intercanine and interpupillary line significantly affect attractiveness is
      unknown. PURPOSE: The purpose of this prospective study was to quantify dental
      and facial esthetics to determine whether smile angulation discrepancies in
      individuals identified as having attractive smiles are smaller than those in the
      average population. MATERIAL AND METHODS: An Internet search for "best smile" and
      "celebrity" identified 108 celebrities (Test group). Photographs showing smiles
      within 10 degrees of a frontal view were gathered. In mannequin testing, small
      head rotation (<10 degrees) was found not to affect the measurements. Photographs
      of dental students were used for the control group. The angulation discrepancy
      between the intercanine and interpupillary line was measured using computer
      software. Groups were compared using the Mann-Whitney U test (alpha=.05).
      RESULTS: Usable photographs were obtained for 94 celebrities (62 women, 32 men)
      and were compared with photographs of 97 dental students (54 women, 43 men).
      Significant (P<.01) differences in angulation discrepancy were found, with
      celebrities having smaller mean angulation discrepancies (0.97 degrees) than
      dental students (1.33 degrees). The differences between men and women were not
      statistically significant (P>.05). CONCLUSIONS: Celebrities identified as having
      "best smile" had significantly smaller mean angulation discrepancies than the
      control group.

PMID- 27881324
TI  - Bacterial adhesion on direct and indirect dental restorative composite resins: An
      in vitro study on a natural biofilm.
AB  - STATEMENT OF PROBLEM: Both direct and indirect techniques are used for dental
      restorations. Which technique should be preferred or whether they are equivalent
      with respect to bacterial adhesion is unclear. PURPOSE: The purpose of this in
      vitro study was to determine the affinity of bacterial biofilm to dental
      restorative composite resins placed directly and indirectly. MATERIAL AND
      METHODS: Five direct composite resins for restorations (Venus Diamond, Adonis,
      Optifil, Enamel Plus HRi, Clearfil Majesty Esthetic) and 3 indirect composite
      resins (Gradia, Estenia, Signum) were selected. The materials were incubated in
      unstimulated whole saliva for 1 day. The biofilms grown were collected and their
      bacterial cells counted. In parallel, the composite resin surface morphology was
      analyzed with atomic force microscopy. Both bacterial cell count and surface
      topography parameters were subjected to statistical analysis (alpha=.05).
      RESULTS: Indirect composite resins showed significantly lower levels than direct
      composite resins for bacterial cell adhesion, (P<.001). No significant
      differences were observed within the direct composite resins (P>.05). However,
      within the indirect composite resins a significantly lower level was found for
      Gradia than Estenia or Signum (P<.01). A partial correlation was observed between
      composite resin roughness and bacterial adhesion when the second and particularly
      the third-order statistical moments of the composite resin height distributions
      were considered. CONCLUSIONS: Indirect dental restorative composite resins were
      found to be less prone to biofilm adhesion than direct composite resins. A
      correlation of bacterial adhesion to surface morphology exists that is described
      by kurtosis; thus, advanced data analysis is required to discover possible
      insights into the biologic effects of morphology.

PMID- 27881325
TI  - Influence of porcelain firing and cementation on the marginal adaptation of metal
      ceramic restorations prepared by different methods.
AB  - STATEMENT OF PROBLEM: Marginal adaptation plays an important role in the survival
      of metal-ceramic restorations. Porcelain firings and cementation may affect the
      adaptation of restorations. Moreover, conventional casting procedures and casting
      imperfections may cause deteriorations in the marginal adaptation of metal
      ceramic restorations. PURPOSE: The purpose of this in vitro study was to compare
      the marginal adaptation after fabrication of the framework, porcelain
      application, and cementation of metal-ceramic restorations prepared by using the
      conventional lost-wax technique, milling, direct metal laser sintering (DMLS),
      and LaserCUSING, a direct process powder-bed system. Alterations in the marginal
      adaptation of the metal frameworks during the fabrication stages and the
      precision of fabrication methods were evaluated. MATERIAL AND METHODS: Forty
      eight metal dies simulating prepared premolar and molar abutment teeth were
      fabricated to investigate marginal adaptation. They were divided into 4 groups
      (n=12) according to the fabrication method used (group C serving as the control
      group: lost-wax method; group M: milling method; group LS: DMLS method; group DP:
      direct process powder-bed method). Sixty marginal discrepancy measurements were
      recorded separately on each abutment tooth after fabrication of the framework,
      porcelain application, and cementation by using a stereomicroscope. Thereafter,
      each group was divided into 3 subgroups according to the measurements recorded in
      each fabrication stage: subgroup F (framework), subgroup P (porcelain
      application), and subgroup C (cementation). Data were statistically analyzed with
      univariate analysis of variance (followed by 1-way ANOVA and Tamhane T2 test
      (alpha=.05). RESULTS: The lowest marginal discrepancy values were observed in
      restorations prepared by using the direct process powder-bed method, and this was
      significantly different (P<.001) from the other methods. The highest marginal
      discrepancy values were recorded after the cementation procedure in all groups.
      CONCLUSIONS: The results showed that the direct process powder-bed method is
      quite successful in terms of marginal adaptation. The marginal discrepancy
      increased after porcelain application and cementation.

PMID- 27881327
TI  - Accuracy of impression scanning compared with stone casts of implant impressions.
AB  - STATEMENT OF PROBLEM: Accurate virtual implant models are a necessity for the
      fabrication of precisely fitting superstructures. PURPOSE: The purpose of this in
      vitro study was to evaluate different methods with which to build an accurate
      virtual model of a 3-dimensional implant in the oral cavity; this model would
      then be used for iterative computer-aided design and computer-aided manufacturing
      (CAD-CAM) procedures. MATERIAL AND METHODS: A titanium master model with 3
      rigidly connected implants was manufactured and digitized with a noncontact
      industrial scanner to obtain a virtual master model. Impressions of the master
      model with the implant position locators (IPL) were made using vinyl siloxanether
      material. The impressions were scanned (Impression scanning technique group). For
      the transfer technique and pick-up technique groups (each group n=20), implant
      analogs were inserted into the impression copings, impressions were made using
      polyether, and casts were poured in Type 4 gypsum. The IPLs were screwed into the
      analogs and scanned. To compare the virtual master model with each virtual test
      model, a CAD interactive software, ATOS professional, was applied. The Kruskal
      Wallis test was subsequently used to determine the overall difference between
      groups, with the Mann-Whitney U test used for pairwise comparisons. Through
      Bonferroni correction, the alpha-level was set to .017. RESULTS: The outcome
      revealed a significant difference among the 3 groups (P<.01) in terms of
      accuracy. With regard to total deviation, for all axes, the transfer technique
      generated the greatest divergence, 0.078 mm (+/-0.022), compared with the master
      model. Deviation with the pick-up technique was 0.041 mm (+/-0.009), with
      impression scanning generating the most accurate models with a deviation of 0.022
      mm (+/-0.007). CONCLUSIONS: The impression scanning method improved the precision
      of CAD-CAM-fabricated superstructures.

PMID- 27881326
TI  - Minimally invasive prosthetic restoration of posterior tooth loss with resin
      bonded, wing-retained, and inlay-retained fixed dental prostheses fabricated from
      monolithic zirconia: A clinical report of two patients.
AB  - The esthetics and biocompatibility of ceramic resin-bonded fixed dental
      prostheses (RBFDPs) are regarded as better than those of their metal ceramic
      counterparts. However, a high incidence of complications in the posterior arches
      of ceramic RBFDPs initiated a process of continuous and evolving design
      development. This clinical report describes 2 successful restorations of a
      missing posterior tooth with monolithic zirconia RBFDPs with 2 different retainer
      designs: retentively prepared adhesive wings and inlays.

PMID- 27881328
TI  - Immunostimulatory capacity of dental casting alloys on endotoxin responsiveness.
AB  - STATEMENT OF PROBLEM: Oral metal exposure has been associated with systemic and
      local adverse reactions, probably due to elemental release from the alloys.
      Although supraphysiological concentrations of salts from dentally applied metals
      can activate innate cells through TLR4 (Ni, Co, Pd) and TLR3 (Au), whether direct
      exposure to solid alloys can also trigger innate immune reactivity is still
      unknown. PURPOSE: The purpose of this in vitro study was to determine whether
      dental cast alloy specimens can activate innate cells and influence their
      responsiveness to bacterial endotoxin. MATERIAL AND METHODS: Human monocyte
      derived dendritic cells (MoDC) and THP-1 cells were cultured on top of different
      alloy specimens (Ni-Cr, Co-Cr, Pd-Cu, Pd-Ag, Ti-6Al-4V, amalgam, gold, and
      stainless steel) or in alloy-exposed culture medium with or without endotoxin
      (lipopolysaccharide [LPS]; Escherichia coli 055:B5). Interleukin-8 (IL-8)
      production was used as the parameter for innate stimulation and evaluated by
      enzyme-linked immunosorbent assay after 24 hours of culture. The statistical
      significance of the effects of various casting alloys on the secretion of IL-8
      was analyzed by using the nonparametric Wilcoxon rank sum test (alpha=.05).
      RESULTS: Dental cast alloys induced IL-8 production in MoDC and THP-1 cells, with
      Au and Pd-Cu providing the strongest stimulation. The alloy-exposed culture media
      tested contained sufficient stimulatory metal ions to induce detectable IL-8
      production in THP-1 cells, except for the Ni-Cr and stainless steel exposed
      media. Au and Pd-Cu alloys were also most effective in potentiating LPS
      responsiveness as measured by IL-8 production. CONCLUSIONS: Using an in vitro
      culture system to expose MoDC and THP-1 cells to different alloy specimens this
      study showed that contact with the solid alloys, in particular when they contain
      Pd or Au, can trigger innate immune responses and augment responsiveness to
      bacterial endotoxin.

PMID- 27881329
TI  - Oral features and computerized rehabilitation of a young patient with CHARGE
      syndrome using minimally invasive long-term interim CAD-CAM restorations.
AB  - Patients with CHARGE syndrome (where CHARGE stands for coloboma of the iris or
      retina, heart defects or cardiac malformations, atresia/stenosis of the choanae,
      retardation of growth and development, genital anomalies, and ear abnormalities)
      present several orofacial anomalies. Their treatment depends on the specific type
      of manifestation. To perform the complex oral rehabilitation and achieve a
      conservative, esthetic, and functional exploration of the definitive treatment
      goal, computer-aided design and computer-aided manufacturing (CAD-CAM) polymers
      can be used as long-term interim restorations. This article reports the treatment
      of a young patient with CHARGE syndrome combined with oral alterations. CAD-CAM
      polymers offer an intermediate treatment with satisfying esthetics and function
      at low biological cost until bone growth is completed. This period facilitates
      additional planning for the definitive restoration.

PMID- 27881330
TI  - Improved digital impressions of edentulous areas.

PMID- 27881331
TI  - In vitro assessment of retention and resistance failure loads of two preparation
      designs for maxillary anterior teeth.
AB  - STATEMENT OF PROBLEM: Parallel labiolingual walls and the preservation of the
      cingulum in anterior tooth preparations have been advocated. However, their
      contribution to retention and resistance form has not been evaluated. PURPOSE:
      The purpose of this in vitro study was to evaluate the retention and resistance
      failure loads of 2 preparation designs for maxillary anterior teeth. MATERIAL AND
      METHODS: Forty metal restorations were fabricated and paired with 40 cobalt
      chromium prepared tooth analogs. Twenty of the specimens had parallel
      buccolingual walls at the cervical part (group PBLW; the control group), whereas
      the remaining 20 had converging buccolingual walls (group CBLW; the experimental
      group). The restorations were cemented to the tooth analogs with a resin-modified
      glass ionomer luting agent. Ten specimens from each group were subjected to
      tensile loading with a universal testing machine; the rest were subjected to
      compression loading until failure. Descriptive statistics and the independent t
      test (alpha=.05) were used to determine the effect of failure loads in the tested
      groups. RESULTS: The independent t test revealed statistically significant
      differences between the tested groups in tensile loading (P<.001) and in
      compressive loading (P<.001). The PBLW group presented a higher tensile failure
      load than the CBLW. On the contrary, the PBLW group presented a smaller
      compression failure load than the CBLW. CONCLUSIONS: Parallelism of the
      buccolingual axial walls in anterior maxillary teeth increased the retention form
      but decreased the resistance form.

PMID- 27881332
TI  - [Herpes simplex virus-mediated RNA interference targeting vesicular glutamate
      transporter 3 attenuates tactile allodynia in mice].
AB  - OBJECTIVE: To construct a replication-deficient herpes simplex virus (HSV-1) for
      delivering a short hairpin RNA (shRNA) targeting vesicular glutamate transporter
      3 (VGLUT3) and observe its effect in alleviating allodynia in mice. METHODS: The
      recombinant HSV-1 vector carrying the shRNA targeting Vglut3 (HSV-1-shvglut3) was
      constructed and inoculated in the sciatic nerve in a mouse model of mechanical
      allodynia to test its analgesia effect. Mechanical allodynia and heat
      hypersensitivity of the mice were tested by von Frey filaments and Hargreaves'
      test, respectively. VGLUT3 expression in the dorsal root ganglion (DRG) was
      evaluated by immunohistochemistry and Western blotting. RESULTS: Following
      inoculation in the sciatic nerve, the HSV vector HSV-1-shvglut3 was retrogradely
      transported to the DRG. Mechanical withdraw thresholds of the mouse models
      receiving HSV-1-shvglut3 inoculation were reversed to nearly the baseline level,
      and VGLUT3 expression in the DRG was down-regulated 2 weeks after vector
      inoculation. The analgesic effect lasted for over 2 weeks in these mice without
      obvious systematic side effects or changes in heat hypersensitivity threshold.
      CONCLUSION: Vglut3 in the DRG is a promising therapeutic target for alleviating
      mechanical allodynia, and HSV-1 vector-mediated RNA interference is safe and
      efficient for inducing long-lasting analgesia after peripheral inoculation of the
      vector.

PMID- 27881333
TI  - [Role of pannexin 1 channels in cisplatin-induced apoptosis in I-10 cells].
AB  - OBJECTIVE: To investigate the role of pannexin 1 channels in cisplatin-induced
      apoptosis in I-10 cells and the mechanisms. METHODS: MTT assay was used to assess
      the cytotoxicity of cisplatin (DDP) in I-10 cells. Annexin V/PI double staining
      and Hoechst 33258 fluorescence staining were employed to detect early- and late
      stage apoptosis of the cells, respectively. Extracellular ATP level and
      intracellular IP3 level in the cells were detected using commercial detection
      kits. RESULTS: I-10 cells exposed to both CBX (a pannexin 1 channel inhibitor)
      and DDP showed a higher cell viability compared with the cells exposed to DDP
      alone (P<0.01). CBX significantly decreased cisplatin-induced early-stage
      apoptosis (P<0.001) and late-stage apoptosis (P<0.01), and cause obvious
      reductions in extracellular ATP and intracellular IP3 levels during cisplatin
      induced apoptosis (P<0.05). CONCLUSION: Pannexin 1 channels participate in
      cisplatin-induced apoptosis in I-10 cells possibly through the ATP/IP3 pathway.

PMID- 27881334
TI  - [Over-expression of receptor-interacting protein 140 in tumor-associated
      macrophages suppresses invasion and proliferation of hepatoma cells in vitro].
AB  - OBJECTIVE: To investigate the role of receptor-interacting protein 140 (RIP140)
      in tumor-associated macrophages (TAMs) in the invasion and proliferation of
      hepatoma cells in vitro. METHODS: Western blotting, qRT-PCR and flow cytometry
      were performed to examine the effects of lentivirus-mediated RIP140 over
      expression in mouse peritoneal macrophages (PMs). Western blotting, qRT-PCR and
      immunofluorescence staining were used to detect the expression of RIP140 in TAMs
      following stimulation of the PMs with hepatocellular carcinoma conditioned medium
      (HCM) for 24 h. The polarization index and the expression of NF-kappaB and IL-6
      were detected using qRT-PCR in TAMs in HCM-stimulated PMs with or without RIP140
      over-expression. Transwell assay and flow cytometry were used to estimate the
      cell invasion and apoptosis. HE staining and immunohistochemical staining were
      used to analyze the effects of RIP140-over-expressing macrophages on the growth
      and tumor formation of H22 cells in BALB/c nude mice. RESULTS: The lentivirus
      vector efficiently mediated RIP140 over-expression in mouse PMs. HCM stimulation
      significantly inhibited RIP140 expression in the TAMs and promoted their M2-like
      polarization. Over-expression of RIP140 in PMs suppressed the invasion and
      induced apoptosis of HCC cells. RIP140 over-expression inhibited HCM-induced M2
      polarization and the activation of NF-kappaB/IL-6 axis in the TAMs, and RIP140-
      overexpressing TAMs obviously suppressed the growth of H22 cell xenograft in nude
      mice. CONCLUSION: Over-expression of RIP140 in TAMs suppresses the growth and
      proliferation of hepatoma cells possibly by inhibiting M2 polarization of the
      TAMs.

PMID- 27881335
TI  - [Health Qigong Wuqinxi improves hydrogen proton magnetic resonance spectra in
      prefrontal cortex and hippocampus in college students with mild depression].
AB  - OBJECTIVE: To investigate the effects of health Qigong Wuqinxi exercise on mild
      depression in college students and analyze the changes in hydrogen proton
      magnetic resonance spectra (1H-MRS) in the prefrontal cortex and hippocampus
      after the exercise. METHODS: Fifty-eight volunteer college students, including 30
      with mild depression and 28 healthy students, were randomized into the
      intervention group and non-intervention group. The students in the intervention
      group were asked to practice health Qigong Wuqinxi training for 12 weeks and
      those in the non-intervention group did not engage in such training. For each
      subject, BECK Depression Self-reported questionnaire (BDI), Hamilton Depression
      rating scale (HAMD) score, and the metabolic parameters of 1H-MRS in the
      prefrontal cortex and hippocampus were evaluated before and after the
      intervention. RESULTS: Before the intervention, the scores of BDI and HAMD in the
      depression group were significantly higher than that in the control group
      (P<0.01), and were lowered obviously after the 12-week intervention (P<0.01).
      Compared with the control group, 1H-MRS in the depression group before
      intervention showed significantly increased NAA/Cr value in the left prefrontal
      cortex, Cho/Cr value in the bilateral hippocampus and the left frontal lobe, and
      Cho/Cr value of the left hippocampus and right frontal lobe (P<0.05) with
      significantly lowered NAA/Cho value in the bilateral prefrontal and Cho/NAA value
      in the right hippocampus (P<0.05). After 12 weeks of intervention, NAA/Cr value
      in the bilateral hippocampus and the NAA/Cho value in the right hippocampus were
      significantly lowered (P<0.05), and NAA/Cho value in the right prefrontal and
      Cho/NAA value in the right hippocampus were significantly increased (P<0.05) in
      the depression group. Before the intervention, Pearson correlation analysis
      showed that the scores of HAMD and BDI were positively correlated with Cho/Cr
      value in the hippocampus and NAA/Cr value in prefrontal lobe (P<0.01) and
      inversely with NAA/Cho in prefrontal lobe and Cho/NAA value in the hippocampus
      (P<0.05); after the intervention, the scores of HAMD and BDI were positively
      correlated with NAA/Cr value in the hippocampus and Cho/Cr value in the left
      hippocampus (P<0.05). CONCLUSION: Exercise of health Qigong Wuqinxi can reduce
      depression scale scores in patients with mild depression and improve the
      metabolic indexes (NAA/Cr and Cho/Cr values) in the prefrontal cortex and the
      hippocampus.

PMID- 27881336
TI  - [Outcome analysis of monozygotic twin pregnancy conceived by assisted
      reproductive techniques].
AB  - OBJECTIVE: To analyze the incidence, management, and outcomes of monozygotic twin
      (MZT) pregnancy conceived by assisted reproductive techniques (ART). METHODS: A
      retrospective analysis was performed of clinical pregnancies after in vitro
      fertilization and embryo transfer (IVF-ET) and introcytoplasmic sperm injection
      and embryo transfer (ICSI-ET) from January, 2010 to June 2015 at our center. We
      investigated the incidence, managements and outcomes of 94 MZT pregnancies.
      Comparison of the pregnancy outcomes was made between the expectantly managed MZT
      pregnancies, dizygotic twin (DZT) pregnancies, monozygotic (MZ)-triplet
      pregnancies with selective embryo reduction (SER) to 2 fetuses and 1 fetus, and
      non-MZ triplet pregnancies with SER to 2 fetuses. RESULTS: Ninety-four MZT
      pregnancies occurred in the total of 6257 clinical pregnancy cycles with an
      incidence of 1.5%. No significant difference was found in the incidence of MZT
      pregnancies between IVF and ICSI cycles or between fresh and thawed cycles
      (P>0.05). Of the 94 MZT pregnancies, 45 were MZT pregnancy cycles, 43 were MZ
      triplet pregnancy cycles, 3 were MZ-quadruplet pregnancy cycles and 3 were
      ectopic pregnancies. The expectantly managed MZT was associated with a
      significantly greater rate of miscarriage and malformation and a lower rate of
      live birth and term birth (P<0.05) in comparison with DZT pregnancy cycles that
      did not undergo SER. Similar outcomes were found between MZ-triplet pregnancies
      with SER to 2 fetuses and MZ-triplet pregnancies with SER to 1 fetus (P>0.05),
      and between MZ-triplets with SER to 2 fetuses and non-MZ triplet pregnancies with
      SER to 2 fetuses (P>0.05). CONCLUSION: ART is associated with a much higher
      incidence of MZT pregnancies than spontaneous conception. MZT pregnancies are at
      high risk of adverse outcomes, and reduction of MZT in multiple pregnancies may
      help to improve the outcomes.

PMID- 27881337
TI  - [Inhibitory effect of Mig-7 silencing by retrovirus-mediated shRNA on
      vasculogenic mimicry, invasion and metastasis of human hepatocellular carcinoma
      cells in vitro].
AB  - OBJECTIVE: To explore the inhibitory effect of migration-inducing gene 7 (Mig-7)
      gene silencing induced by retroviral-mediated small hairpin RNA (shRNA) on
      vasculogenic mimicry (VM), invasion and metastasis of human hepatocellular
      carcinoma (HCC) cells in vitro. METHODS: Two target sequences (Mig-7 shRNA-1 and
      Mig-7 shRNA-2) and one negative control sequence (Mig-7 shRNA-N) were
      synthesized. The recombinant retroviral vectors carrying Mig-7 shRNA were
      constructed, and HCC cell line MHCC-97H were transfected with Mig-7 shRNA-1, Mig
      7 shRNA-2, Mig-7 shRNA-N, or the empty vector, or treated with 125 ug/mL
      recombinant human endostatin (ES). Mig-7 expression in the treated cells was
      detected using semi-quantitative PCR and Western blotting. The inhibitory effect
      of Mig-7 silencing on VM formation was investigated in a 3-dimensional cell
      culture system; the changes in cell adhesion, invasion and migration were
      assessed with intercellular adhesion assay, Transwell invasion assay and
      Transwell migration assay, respectively. RESULTS: The expression of Mig-7 at both
      mRNA and protein levels decreased significantly, VM formation, invasion and
      metastasis were suppressed, while intercellular adhesion increased significantly
      in MHCC-97H cells in Mig-7 shRNA-1 and Mig-7 shRNA-2 groups (P<0.05); such
      changes were not observed in cells transfected with Mig-7 shRNA-N or the empty
      vector, nor in cells treated with ES. CONCLUSIONS: Mig-7 silencing by retroviral
      mediated shRNA significantly inhibits VM formation, invasion and metastasis and
      increases the intercellular adhesion of the HCC cells, while ES does not have
      such inhibitory effects.

PMID- 27881338
TI  - [Plasma metabonomics of Guifu Dihuang Wan in the treatment of yang deficiency].
AB  - OBJECTIVE: To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of
      yang deficiency and explore the underlying molecular mechanism. METHODS: Sixty
      two participants without diseases were randomized into control group (n=31) and
      experimental group (n=31) and were given lifestyle intervention additional GFDHW
      treatment for a month. NMR technology was used for metabonomics analysis.
      RESULTS: Intervention with GFDHW resulted in significantly decreased conversion
      scores of yang deficiency in the experimental group compared with the control
      group (P<0.005). The concentrations of lactate, valine, proline, arginine and 3
      hydroxybutyrate were increased in the plasma of yang-deficient subjects after
      lifestyle intervention. GFDHW treatment with lifestyle intervention significantly
      increased the concentrations of lactate, valine, proline, arginine and 3
      hydroxybutyrate and also the levels of alanine, glutamine, alpha glucose,
      isoleucine, betaine and propylene glycol. CONCLUSION: GFDHW treatment improves
      yang deficiency possibly by increasing the concentrations of alanine, glutamine,
      alpha glucose, isoleucine, betaine and propylene glycol and promoting energy
      metabolism of the body.

PMID- 27881339
TI  - [Comparison of TaqMan and Allglo probe in fluorescence quantitative RT-PCR
      detection of simian immunodeficiency virus].
AB  - OBJECTIVE: To compare the sensitivity and reproducibility of Allglo and TaqMan
      probe in the detection of simian immunodeficiency virus (SIV) using fluorescence
      quantitative RT-PCR (QPCR). METHODS: The reference sample of SIV was diluted to 6
      gradient concentrations; at each concentration 12 samples were tested to analyze
      the variations within batches, and each sample was tested for 12 times for
      analysis of variations between batches by QRT-PCR using TaqMan probe and Allglo
      probe. The results of QPCR using the two probes were analyzed with ABI7300 PCR
      system software. RESULTS: In QPCR using TaqMan and Allglo probe, the lower limit
      of sensitivity for SIV detection was both 50 copies/mL. Assessment of the
      reproducibility of the tests showed that the maximum and minimum coefficients of
      variation between batches were 0.63% and 0.33% with Allglo probe, respectively,
      as compared with 1.33% and 0.2% with TaqMan probe. The maximum and minimum
      coefficients of inter-batch variation was 1.77% and 0.95% with Allglo probe,
      respectively, as compared with 1.86% and 1.03% with TaqMan probe. CONCLUSION:
      Allglo probe shows a better performance then TaqMan probe in detection of SIV
      QPCR.

PMID- 27881340
TI  - [Expressions of Ras and Sos1 in epithelial ovarian cancer tissues and their
      clinical significance].
AB  - OBJECTIVE: To detect the expressions of Ras and Sos1 proteins in human epithelial
      ovarian cancer (EOC) tissues and explore their correlation with the
      clinicopathological features of the patients. METHODS: The expressions of Ras and
      Sos1 proteins were detected immunohistochemically in 62 EOC tissues, 5 borderline
      ovarian cancer tissues, 15 benign epithelial ovarian neoplasm tissues, and 18
      normal ovarian tissues. RESULTS: The EOC tissues showed significantly higher
      expression levels of both Ras and Sos1 than the other tissues tested (P<0.05). In
      EOC tissues, Ras and Sos1 proteins were expressed mostly on the cell membrane and
      in the cytoplasm. The expression level of Ras was correlated with pathological
      types of the tumor (P<0.05) and was the highest in serous cystadenomcarcinoma;
      Sos1 expression did not show significant correlation with the clinicopathological
      indexes of the patients. High expressions of both Ras and Sos1 proteins were
      associated with shorter progression-free survival of the patients, but this
      association was not statistically significant. CONCLUSIONS: Ras and Sos1 protein
      may participate in in the occurrence and development of EOC. The tissue-specific
      variation of Ras expression can lend support to a specific diagnosis of ovarian
      serous adenocarcinoma. The association of Ras and Sos1 protein expression with
      the tumor-free survival time of the patients awaits further investigation with a
      larger sample size.

PMID- 27881341
TI  - [Low-frequency pulsed electromagnetic fields promotes rat osteoblast
      differentiation in vitro through cAMP/PKA signal pathway].
AB  - OBJECTIVE: To study whether low-frequency pulsed electromagnetic fields promotes
      the differentiation of cultured rat osteoblasts through the cAMP/PKA signal
      pathway. METHODS: Rat calvarial osteoblasts isolated by enzyme digestion were
      exposed to 50 Hz 0.6 mT low-frequency pulsed electromagnetic field for varying
      lengths of time, and the concentration of cAMP and levels of phosphorylated PKA
      in the cells were assayed. In cells treated with DDA to inhibit the activity of
      adenylate cyclase, the changes of ALP activity and transcription of osteogenic
      gene were detected after exposure to low-frequency pulsed electromagnetic field.
      The changes of osteogenic gene transcription and protein expression were tested
      in the osteoblasts pretreated with KT5720 in response to low-frequency pulsed
      electromagnetic field exposure. RESULTS: The intracellular cAMP concentration in
      the cells increased significantly at 20 min during exposure to low-frequency
      pulsed electromagnetic field, began to decrease at 40 min during the exposure,
      and increased again after a 2-h exposure; the same pattern of variation was also
      observed in p-PKA level. Application of DDA and KT5720 pretreatment both
      suppressed the increase in ALP activity and osteogenic gene transcription induced
      by electromagnetic field exposure. CONCLUSION: Low- frequency pulsed
      electromagnetic field exposure improves the differentiation of cultured rat
      osteoblasts by activating cAMP/PKA signal pathway.

PMID- 27881342
TI  - [Factors affecting maternal physical activities: an analysis based on the
      structural equation modeling].
AB  - OBJECTIVE: To analyze the factors affecting maternal physical activities at
      different stages among pregnant women. METHODS: Self-designed questionnaires were
      used to investigate the physical activities of women in different stages,
      including 650 in the first, 650 in the second, and 750 in the third trimester of
      pregnancy. The factors affecting maternal physical activities were analyzed using
      the structural equation model that comprised 4 latent variables (attitude, norm,
      behavioral attention and behavior) with observed variables that matched the
      latent variables. RESULTS: The participants ranged from 18 to 35 years of age.
      The women and their husbands, but not their mothers or mothers-in-law, were all
      well educated. The caregiver during pregnancy was mostly the mother followed by
      the husband. For traveling, the women in the first, second and third trimesters
      preferred walking, bus, and personal escort, respectively; the main physical
      activity was walking in all trimesters, and the women in different trimester were
      mostly sedentary, a greater intensity of exercise was associated with less
      exercise time. Structural equation modeling (SEM) analysis showed that the
      physical activities of pregnant women was affected by behavioral intention (with
      standardized regression coefficient of 0.372); attitude and subjective norms
      affected physical activity by indirectly influencing the behavior intention
      (standardized regression coefficients of 0.140 and 0.669). CONCLUSIONS: The
      pregnant women in different stages have inappropriate physical activities with
      insufficient exercise time and intensity. The subjective norms affects the
      physical activities of the pregnant women by influencing their attitudes and
      behavior intention indirectly, suggesting the need of health education of the
      caregivers during pregnancy.

PMID- 27881343
TI  - [Surgical management of proximal anterior cerebral artery (A1) aneurysms].
AB  - OBJECTIVE: To review our experience in surgical management of proximal anterior
      cerebral artery (A1) aneurysms in 23 patients. METHODS: Between January, 2004 and
      December, 2014, 23 patients (1.6%) with A1 aneurysms diagnosed by CTA or DSA were
      treated surgically. The "3H" therapy was adopted for postoperative prevention of
      cerebrovascular spasm. All the patients were followed up and examined with
      cerebrovascular CTA at 6, 12, 48 and 60 months after the operation with their
      Glasgow Outcome Scale score recorded. RESULTS: The patients consisted of 15 men
      and 8 women with an age range of 16 to 72 years (mean 51.3 years). The average
      diameter of the aneurysms was 5.8 mm, ranging from 3.2 to 9.7 mm. Twenty-two
      saccular aneurysms were found in these patients; 21 patients presented with SAH
      and two had vascular malformation. All the A1 aneurysms were managed through the
      pterional approach, and the mean postoperative Glasgow Outcome Scale score was
      4.8. CONCLUSION: Thorough analysis of the angiographic data is essential for the
      diagnosis and treatment of A1 aneurysms. Preservation of the perforators and
      prevention of aneurysm rupture are critical during the surgery. Full exposure of
      the Sylvian fissure and temporary occlusion of the parent artery ensures safe and
      effective dissection of A1 aneurysms.

PMID- 27881344
TI  - [Value of urinary liver fatty acid-binding protein in assessing severity of brain
      trauma and predicting acute kidney injury].
AB  - OBJECTIVE: To assess the value of urinary liver-type fatty acid-binding protein
      (L-FABP) in early assessment of the severity of traumatic brain injury and in
      predicting the occurrence of acute kidney injury (AKI) following the brain
      injury. METHODS: Sixty-five patients with traumatic brain injury patients were
      divided into 4 groups according to their Glasgow coma scale (GCS) scores. Blood
      and urine samples were collected at 2, 6, 12, 24, 48 and 72 h after the injury to
      detect serum creatinine (SCr) level using biochemical analyzer and urinary L-FABP
      using enzyme-linked immunosorbent assay (ELISA), with samples from 15 healthy
      adults as controls. The correlations were analyzed among SCr, urinary L-FABP, GCS
      score upon admission and AKI occurrence. RESULTS: The patients with moderate to
      severe brain injuries showed significantly higher SCr and urinary L-FABP levels
      than the control group (P<0.05). GCS score of the patients was inversely
      correlated with the levels of SCr and urinary L-FABP (P<0.05), and the changes
      were more prominent in urinary L-FABP than in SCr. The incidence of AKI was
      21.54% in these patients. In patients with AKI, urinary L-FABP reached the peak
      level as soon as 6 h after the injury, as compared with 24 to 48 h when peak SCr
      level occurred. CONCLUSION: Urinary L-FABP can be used as a marker for early
      assessment of the severity of traumatic brain injury and for predicting the
      occurrence of AKI following the injury.

PMID- 27881345
TI  - [Extraction and identification of semen-derived exosomes using PEG6000].
AB  - OBJECTIVE: To extract and identify semen-derived exosome using PEG6000. METHODS:
      Exosomes were extracted from semen specimens from 6 healthy volunteers with step
      by-step centrifugations and ultracentrifugation prior to 8% PEG6000 enrichment.
      The extracted exosomes were characterized by transmission electron microscopy
      (TEM), nanoparticle tracking analysis (NTA) and Western blotting. RESULTS: The
      pellets obtained were round or elliptic membrane vesicles 30 to 150 nm in
      diameter with intact double membranes and contained low electron density
      material. The pellets expressed CD63, ALIX and TSG101 molecules but not calnexin
      that was expressed in sperm cells. CONCLUSION: The PEG6000-based method for
      extraction of exosomes from semen samples facilitates future studies of seminal
      exosomes.

PMID- 27881346
TI  - [Synergistic analgesic effect of choline and parecoxib sodium in mice and the
      mechanism].
AB  - OBJECTIVE: To investigate the synergistic analgesic effect of choline and
      parecoxib sodium and study its mechanism. METHODS: In male Kunming mice with
      acetic acid-induced writhing, the ED50 of choline and parecoxib sodium
      (administered via the tail vein at 2 h and 30 min before modeling, respectively)
      and their combined use were determined. In saline (control) group, ED50 choline
      (C) group, ED50 parecoxib sodium (P) group, and 1/2ED50 choline and parecoxib
      sodium (1/2[C+P]) group, blood samples were collected from the eyeball 10 min
      after intraperitoneal administration of acetic acid to detect the levels of IL-1,
      TNF-alpha, PGE2, NF-kappaB, and I-kappaB levels using ELISA kits. RESULTS: In the
      acetic acid-induced writhing model, the ED50 of choline and parecoxib sodium was
      8.64 and 6.33 mg/kg, and when combined, their ED50 was 2.13 and 1.56 mg/kg,
      respectively. The isobolograms of parecoxib sodium and choline showed that the
      measured ED50 of the two drugs combined was below the theoretical ED50 value
      (P<0.05) with a combination index (CI) of <0.9. Compared with the control group,
      C group, P group, and 1/2 (C+P) group all showed significantly lowered IL-1 and
      TNF-alpha levels (P<0.05), especially in 1/2 (C+P) group (P<0.05). PGE2 level was
      significantly lower in P group and 1/2 (C+P) group compared with the control
      group (P<0.05). NF-kappaB and I-kappaB levels were significantly lowered in C, P,
      and 1/2 (C+P) groups (P<0.05), and the reduction was the most obvious in 1/2
      (C+P) group (P<0.05). CONCLUSION: Choline and parecoxib sodium has a synergistic
      analgesic effect, and their interactions may involve the in vivo expression of NF
      kappaB.

PMID- 27881347
TI  - [Effect of rhynchophylline on behaviors of methamphetamine-dependent zebrafish
      and the mechanism].
AB  - OBJECTIVE: To observe the effect of rhynchophylline on methamphetamine-dependent
      zebrafish and explore the possible mechanism. METHODS: Zebrafish were divided
      into control group, amphetamine group, low- (50 mg/kg) and high (100 mg/kg)-dose
      rhynchophylline groups, and ketamine (150 mg/kg) group. Conditioned place
      preference (CPP) was induced in zebrafish with methamphetamine, and the staying
      time in the drug box and the tracking map of the zebrafish were observed with
      Noldus Ethovision XT system. The protein expressions of TH, NR2B and GLUR2 in the
      brain of zebrafish with CPP were detected with Western blotting. RESULTS:
      Compared with the control group, zebrafish in methamphetamine group showed
      significant variations in the staying time and swimming distance in the drug box
      after conditioning (P<0.05) with obvious alterations of NR2B, TH and GLUR2
      expressions in the brain (P<0.05). Treatment of methamphetamine-dependent
      zebrafish with high-dose rhynchophylline significantly reduced the variations in
      the staying time and swimming distance in the drug box (P<0.05) and in the
      expressions of NR2B, TH and GLUR2 in the brain (P<0.05). CONCLUSION:
      Rhynchophylline can inhibit methamphetamine dependence in zebrafish, the
      mechanism of which may involve the expressions of TH, NR2B and GLUR2 proteins in
      the brain.

PMID- 27881348
TI  - [Analysis of clinical factors correlating with osteoporosis in patients with type
      2 diabetes mellitus].
AB  - OBJECTIVE: To analyze the clinical factors that contribute to lowered bone
      mineral density (BMD) of the lumbar vertebrae in type 2 diabetic patients.
      METHODS: Forty type 2 diabetic patients with osteoporosis and 40 age- and gender
      matched healthy individuals, selected using propensity score method, were
      examined for BMD of the L1 to L4 vertebrae and the left femur. Age, gender,
      course of the disease, body mass index (BMI), fasting blood glucose, serum
      calcium, serum phosphate, urinary calcium, and urinary phosphate were compared
      between the two groups. RESULTS: BMD of the L1 to L4 vertebras was significantly
      lower in the diabetic group than in the healthy individuals (P<0.05). In the
      diabetic patients, BMD showed an obvious difference between male and female
      patients and was negatively correlated with the course of the disease but
      positively with BMI, fasting blood glucose, urinary calcium and urinary
      phosphate; BMD was not correlated with age, serum calcium or serum phosphate in
      these patients. CONCLUSION: Osteoporosis in type 2 diabetic patients is closely
      related with gender, BMI, course of the disease and poorly controlled glucose
      level.

PMID- 27881349
TI  - [Diagnosis of drowning by detecting gyrB and 16S rRNA genes of Aeromonas
      hydrophila using PCR-capillary electrophoresis].
AB  - OBJECTIVE: To establish a method for diagnosis of freshwater drowning by
      amplifying gyrB and 16S rRNA genes of Aeromonas hydrophila using PCR coupled with
      capillary electrophoresis (CE). METHODS: DNA samples were extracted from human,
      18 planktons (including Candida albicans, Aeromonas hydrophila, and 16 species of
      algae), and 30 cases of tissue samples (including the lung, liver, and kidney,
      all examined with microwave digestion-vacuum filtration-automated scanning
      electron microscopy) from human cadavers, including 28 freshwater drowning
      victims and 2 with natural death. The DNA samples were amplified with the primer
      AH (for gyrB gene) and primer Ah (for 16S rRNA gene), and the products were
      analyzed with CE. RESULTS: PCR amplification followed by CE yielded negative
      results for DNA of human, Candida albicans and 16 species of algae, whereas a
      positive result was found for Aeromonas hydrophila DNA with PCR products of 195
      bp (with primer AH) and 350 bp (with primer Ah). In the 28 drowning cases, the
      detection rates of Aeromonas hydrophila using primer AH were 96.4% in the lung
      tissue, 71.4% in the liver tissue, and 60.7% in the kidney, as compared with the
      rates of 75.0%, 42.9%, and 32.1% using primer Ah, respectively. The positive
      rates for Aeromonas hydrophila in the organs of the drowning victims were 82.1%
      and 53.6% with primer AH and primer Ah, respectively. The detection showed
      negative results in the 2 cases of natural deaths. The two primers produced
      significantly different detection rates of Aeromonas hydrophila (P<0.05).
      CONCLUSION: PCR coupled with CE for detecting gyrB gene of Aeromonas hydrophila
      has a high sensitivity in assisting a diagnosis of freshwater drowning. Detection
      of both the gyrB gene and 16S rRNA gene of Aeromonas hydrophila can yield more
      convincing evidence of the diagnosis of freshwater drowning.

PMID- 27881351
TI  - [Role of CaN-NFATc3 pathway in abdominal aorta restenosis following ballon
      dilatation in rats].
AB  - OBJECTIVE: To investegate the role of calcineurin (CaN) and its downstream
      nuclear factor of activated T-cells (NFATc3) in abdominal aorta restenosis
      following balloon dilatation in rats. METHODS: SD rats were randomly divided into
      sham-operated group, balloon group and cyclosporine A (CsA) group. The rats in
      the latter two groups were subjected to abdominal aorta injury with balloon
      dilatation, and those in CsA group were treated with CsA at the daily dose of
      12.5 mg/kg from 3 days before the surgery to the end of the experiment. Thirty
      days afer the injury, histological analysis of the arterial wall was carried out
      with HE staining and immunohistochemistry. The expressions of CaN and NFATc3 in
      the abdominal aortas were detected with rea1-time PCR, and serum concentration of
      MCP-1 was determined using enzyme-linked immunosorbent assay. RESULTS: Intimal
      hyperplasia with irregular thickness of the neointima was observed in the aorta
      of rats with ballon injury. In rats with CsA treatment, the area of the intimal
      layers and the ratio of the intimal to the medial layers were obviously lower
      than those in the balloon injury group (P<0.05). Compared to those in the sham
      operated group, the expressions of calcineurin protein and mRNA and NFATc3 mRNA
      in the arterial wall and serum level of MCP-1 increased significantly in the
      ballon injury group (P<0.05). CsA treatment significantly suppressed aorta
      restenosis and the alterations of CaN, NFATc3 and serum MCP-1 induced by ballon
      dilatation (P<0.05). CONCLUSIONS: CaN-NFATc3 signal transduction pathway mediates
      restenosis of rat abdominal aorta following ballon dilatation, and CsA can
      attenuate the restenosis by suppressing this pathway.

PMID- 27881350
TI  - [Geographical distribution of the Serum creatinine reference values of healthy
      adults].
AB  - OBJECTIVE: To explore the relationship between serum creatinine (Scr) reference
      values in healthy adults and geographic factors and provide evidence for
      establishing Scr reference values in different regions. METHODS: We collected 29
      697 Scr reference values from healthy adults measured by 347 medical facilities
      from 23 provinces, 4 municipalities and 5 autonomous regions. We chose 23
      geographical factors and analyzed their correlation with Scr reference values to
      identify the factors correlated significantly with Scr reference values.
      According to the Principal component analysis and Ridge regression analysis, two
      predictive models were constructed and the optimal model was chosen after
      comparison of the two model's fitting degree of predicted results and measured
      results. The distribution map of Scr reference values was drawn using the Kriging
      interpolation method. RESULTS: Seven geographic factors, including latitude,
      annual sunshine duration, annual average temperature, annual average relative
      humidity, annual precipitation, annual temperature range and topsoil (silt)
      cation exchange capacity were found to correlate significantly with Scr reference
      values. The overall distribution of Scr reference values featured a pattern that
      the values were high in the south and low in the north, varying consistently with
      the latitude change. CONCLUSION: The data of the geographic factors in a given
      region allows the prediction of the Scr values in healthy adults. Analysis of
      these geographical factors can facilitate the determination of the reference
      values specific to a region to improve the accuracy for clinical diagnoses.

PMID- 27881353
TI  - [Correlation of homocysteine with diabetic microangiopathy and the change after
      drug intervention].
AB  - OBJECTIVE: To explore the correlation of homocysteine with diabetic
      microangiopathy and the change after drug intervention. METHODS: A total of 200
      patients with type 2 diabetes were selected between January and December 2013.
      The patients were divide into group of no microvascular disease and group of
      microvascular lesion according to the complications. Blood lipid, blood glucose,
      renal function and serum homocysteine were deteced pre-treatment and after 6
      months treatment.A total of 100 cases of healthy subjects with physical
      examination over the same period were selected as control group according to the
      principle of age and gender matching. RESULTS: SBP, DBP, TG, TC, LDL, FBG, 2
      hPBG, HbA1, SUN, SCr and HCY in group of no microvascular disease and group of
      microvascular lesion were significantly higher than that in control
      group(P<0.01), while HDL were significantly lower(P<0.01); SBPDBP,SUN,SCr and HCY
      in group of microvascular lesion were significantly higher than that in group of
      no microvascular disease(P<0.01); Multi factor Logistic regression analysis
      showed blood pressure, urea nitrogen, serum creatinine and homocysteine levels
      are risk factors for microvascular complications in patients with diabetes
      mellitus; HCY after treatment were significantly lower than that before treatment
      in group of no microvascular disease and group of microvascular lesion
      than(P<0.01). CONCLUSION: High homocysteine levels are risk factor of diabetic
      microvascular disease, and the homocysteine levels can be reduced after
      treatment.

PMID- 27881352
TI  - [Efficacy and safety of drug-coated balloon angioplasty in treatment of lower
      extremity arterial occlusive disease: a meta-analysis of 11 trials].
AB  - OBJECTIVE: To evaluate the efficacy and safety of drug-coated balloon (DCB)
      angioplasty versus uncoated balloon (UCB) angioplasty in treatment of lower
      extremity arterial occlusive disease (LEAOD). METHODS: Randomized controlled
      trial comparing DCB and UCB angioplasty for treatment of LEAOD were searched in
      online databases. Literature screening and quality assessment was carried out
      according to the established inclusion criteria and exclusion criteria.
      Restenosis rate at 6 months after surgery, late lumen loss, target lesion
      revascularization rate, patency rate, mortality rate, and amputation rate at 1
      year after operation were compared between DCB group and UCB group using RevMan
      5.3 software. RESULTS: Eleven trials involving a total of 1853 patients with 2150
      lesions were included, with 1110 patients (1288 lesions) in DCB group and 743
      patients (862 lesions ) in UCB group. Meta-analysis showed that the restenosis
      rate at 6 months after the operation (15.2% vs 39.0%; OR: 0.28; 95%CI: 0.17 to
      0.48; P<0.00001), late lumen loss (range -0.05 to 0.56 vs 0.54 to 1.7; WMD: 
      0.57; 95%CI: -0.93 to -0.21), and target lesion revascularization rate at 1 year
      after operation (13.0% vs 28.1%; OR: 0.39; 95%CI: 0.23 to 0.64; P=0.0002) were
      significantly lower in DCB group than in UCB group. The patency rate at 1 year
      after the operation was significantly higher in DCB group than in UCB group
      (71.8% vs 52.9%; OR: 2.32; 95%CI: 1.21 to 4.43; P=0.001). The mortality rate
      (4.8% vs 5.0%; OR: 1.00; 95%CI: 0.62 to 1.63; P=0.99) and amputation rate at 1
      year after the operation (3.4% vs 2.9%; OR:1.41; 95%CI: 0.74 to 2.70; P=0.30) did
      not differ significantly between DCB and UCB group. CONCLUSION: DCB angioplasty
      is more effective than UCB angioplasty in endovascular treatment of LEAOD with
      similar treatment safety.

PMID- 27881354
TI  - [Analysis of immune suppression in patients with systemic lupus erythematosus
      complicated by herpes zoster virus infection].
AB  - OBJECTIVE: To explore the changes in cellular immune function and the safety of
      physical therapy in patients with systemic lupus erythematosus (SLE) complicated
      by herpes zoster (HZ) virus infection. Methods A retrospective analysis was
      conducted among 10 SLE pateints with HZ virus infection, with 30 SLE patients
      without HZ infection as the control group. The results of routine laboratory
      tests and T lymphocyte subset counts (before and during infection and after cure
      of infection) were compared between the two groups. RESULTS: The proportion of
      patients with significantly increased absolute neutrophil count and white blood
      cell count before HZ infection, and those with decreased lymphocyte percentage
      and elevated C-reactive protein during infection differed significantly between
      the two groups (P<0.05). Before HZ infection, the proportions of patients with
      increased CD3+%, decreased CD16+CD56+%, abnormal 4/8 ratio (P<0.01) and those
      with increased CD8+% and CD8+ count and decreased CD16+CD56+ count differed
      significantly between the two groups (P<0.05). During HZ infection, the
      proportion of patients with increased CD3+% and CD8+% and decreased CD4+% and 4/8
      ratio count (P<0.05) and those with decreased CD16+CD56+% and increased CD8+
      count differed significantly between the two groups (P<0.01). After cure of HZ
      infection, the proportion of patients with decreased CD16+CD56+% was
      significantly different between the two groups (P<0.01). The treatment time of HZ
      infection averaged 5?1.3 days with a cure rate of 100% postherpetic neuralgia
      occurred in none of the patients after the treatment. CONCLUSION: Patients with
      SLE complicated by HZ infection are in an immunosuppressive state, suggesting the
      need of monitoring T lymphocyte subsets in SLE treatment. The combined use of
      antiviral drugs and physical therapy can be safe and effective for treatment of
      SLE complicated by HZ infection.

PMID- 27881355
TI  - [Comparison of open versus laparoscopic surgeries for adrenal tumor: a meta
      analysis].
AB  - OBJECTIVE: To systematically review the effectiveness and safety of open and
      laparoscopic surgeries for treatment of adrenal tumors. METHODS: The online
      databases including CNKI, PUBMED, SinoMed, EBSCO, Springerlink, WanFang Data, and
      VIP were searched for clinical trials published from 1999 to 2016. A meta
      analysis was performed using RevMan 5.2 software. RESULTS: A total of 2340
      patients in 25 trials were included. The results of meta-analysis showed that
      laparoscopic surgery was better than open surgery in terms of intestinal function
      recovery time (OR=-0.96, 95%CI [-1.22, -0.70] P<0.000 01), hospitalization time
      (OR=-3.48, 95%CI [-4.13, -2.78], P<0.000 01), complications (OR=0.22, 95%CI
      [0.14, 0.35], P<0.0001), and volume of blood loss (OR=-104.77, 95%CI [-138.95, 
      70.60], P<0.000 01). There was no significant difference in the surgery cost
      between open and laparoscopic surgeries. CONCLUSION: Laparoscopic surgery is
      superior to open surgery for treatment of adrenal tumors for shorter intestinal
      function recovery time, surgery duration, and hospitalization time and less
      complications and blood loss.

PMID- 27881356
TI  - [Correlation analysis of G870A CCND1 gene polymorphism with digestive system
      tumors].
AB  - OBJECTIVE: To study the correlation of G870A CCND1 gene polymorphism and
      digestive system tumors. METHODS: From August 2010 to August 2014, 164 digestive
      system cancer patients (including 82 patients with gastric cancer and 82 with
      colorectal cancer) and 82 healthy subjects (control group) were examined with PCR
      restriction fragment length polymorphism (PCR-RFLP). The distribution of CCND1
      gene G870A frequency in the 3 groups and its association with tumor staging and
      grading were analyzed. RESULTS: The frequencies of the GG, GA and AA genotypes in
      G870A CCND1 gene loci in patients with gastric cancer and colorectal cancer
      differed significantly from those in the control group (P<0.05). G870A CCND1 gene
      polymorphism was closely associated with an increased risk of digestive system
      tumors (P<0.05). The GA and AA genotypes were associated with a significantly
      higher risk of digestive system cancer risk than the GG genotype (P<0.05), and
      their frequencies were significantly higher in patients with tumors of higher
      pathological grade and in those in advanced tumor stages (P<0.05). CONCLUSION:
      G870A CCND1 gene polymorphism is associated with the risk of digestive system
      tumors. The allele A is associated with an increased risk of digestive system
      tumors and correlated with the tumor differentiation and staging of the tumor.

PMID- 27881358
TI  - Development of a Mobile Phone App to Support Self-Monitoring of Emotional Well
      Being: A Mental Health Digital Innovation.
AB  - BACKGROUND: Emotional well-being is a primary component of mental health and well
      being. Monitoring changes in emotional state daily over extended periods is,
      however, difficult using traditional methodologies. Providing mental health
      support is also challenging when approximately only 1 in 2 people with mental
      health issues seek professional help. Mobile phone technology offers a
      sustainable means of enhancing self-management of emotional well-being.
      OBJECTIVE: This paper aims to describe the development of a mobile phone tool
      designed to monitor emotional changes in a natural everyday context and in real
      time. METHODS: This evidence-informed mobile phone app monitors emotional mental
      health and well-being, and it provides links to mental health organization
      websites and resources. The app obtains data via self-report psychological
      questionnaires, experience sampling methodology (ESM), and automated behavioral
      data collection. RESULTS: Feedback from 11 individuals (age range 16-52 years; 4
      males, 7 females), who tested the app over 30 days, confirmed via survey and
      focus group methods that the app was functional and usable. CONCLUSIONS:
      Recommendations for future researchers and developers of mental health apps to be
      used for research are also presented. The methodology described in this paper
      offers a powerful tool for a range of potential mental health research studies
      and provides a valuable standard against which development of future mental
      health apps should be considered.

PMID- 27881359
TI  - Feasibility and Effectiveness of Using Wearable Activity Trackers in Youth: A
      Systematic Review.
AB  - BACKGROUND: The proliferation and popularity of wearable activity trackers (eg,
      Fitbit, Jawbone, Misfit) may present an opportunity to integrate such technology
      into physical activity interventions. While several systematic reviews have
      reported intervention effects of using wearable activity trackers on adults'
      physical activity levels, none to date have focused specifically on children and
      adolescents. OBJECTIVE: The aim of this review was to examine the effectiveness
      of wearable activity trackers as a tool for increasing children's and
      adolescents' physical activity levels. We also examined the feasibility of using
      such technology in younger populations (age range 5-19 years). METHODS: We
      conducted a systematic search of 5 electronic databases, reference lists, and
      personal archives to identify articles published up until August 2016 that met
      the inclusion criteria. Articles were included if they (1) specifically examined
      the use of a wearable device within an intervention or a feasibility study; (2)
      included participants aged 5-19 years old; (3) had a measure of physical activity
      as an outcome variable for intervention studies; (4) reported process data
      concerning the feasibility of the device in feasibility studies; and (5) were
      published in English. Data were analyzed in August 2016. RESULTS: In total, we
      identified and analyzed 5 studies (3 intervention, 2 feasibility). Intervention
      delivery ranged from 19 days to 3 months, with only 1 study using a randomized
      controlled trial design. Wearable activity trackers were typically combined with
      other intervention approaches such as goal setting and researcher feedback. While
      intervention effects were generally positive, the reported differences were
      largely nonsignificant. The feasibility studies indicated that monitor comfort
      and design and feedback features were important factors to children and
      adolescents. CONCLUSIONS: There is a paucity of research concerning the
      effectiveness and feasibility of wearable activity trackers as a tool for
      increasing children's and adolescents' physical activity levels. While there are
      some preliminary data to suggest these devices may have the potential to increase
      activity levels through self-monitoring and goal setting in the short term, more
      research is needed to establish longer-term effects on behavior.

PMID- 27881357
TI  - Social Networking Sites, Depression, and Anxiety: A Systematic Review.
AB  - BACKGROUND: Social networking sites (SNSs) have become a pervasive part of modern
      culture, which may also affect mental health. OBJECTIVE: The aim of this
      systematic review was to identify and summarize research examining depression and
      anxiety in the context of SNSs. It also aimed to identify studies that complement
      the assessment of mental illness with measures of well-being and examine
      moderators and mediators that add to the complexity of this environment. METHODS:
      A multidatabase search was performed. Papers published between January 2005 and
      June 2016 relevant to mental illness (depression and anxiety only) were extracted
      and reviewed. RESULTS: Positive interactions, social support, and social
      connectedness on SNSs were consistently related to lower levels of depression and
      anxiety, whereas negative interaction and social comparisons on SNSs were related
      to higher levels of depression and anxiety. SNS use related to less loneliness
      and greater self-esteem and life satisfaction. Findings were mixed for frequency
      of SNS use and number of SNS friends. Different patterns in the way individuals
      with depression and individuals with social anxiety engage with SNSs are
      beginning to emerge. CONCLUSIONS: The systematic review revealed many mixed
      findings between depression, anxiety, and SNS use. Methodology has predominantly
      focused on self-report cross-sectional approaches; future research will benefit
      from leveraging real-time SNS data over time. The evidence suggests that SNS use
      correlates with mental illness and well-being; however, whether this effect is
      beneficial or detrimental depends at least partly on the quality of social
      factors in the SNS environment. Understanding these relationships will lead to
      better utilization of SNSs in their potential to positively influence mental
      health.

PMID- 27881360
TI  - An Observational Registry of Carotid Endarterectomy and Carotid Artery Stenting
      in Brazil: Study Protocol.
AB  - BACKGROUND: Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are
      alternative strategies for stroke prevention in patients with atherosclerotic
      carotid disease. CEA has been considered the first-line treatment for carotid
      stenosis worldwide, and the safety and efficacy of CAS compared to CEA remains in
      question. OBJECTIVE: The purpose of this study is to compare the practice and
      outcomes of CAS and CEA in a real-world setting within public university
      hospitals in Brazil. METHODS: This study will be a prospective 5-year analysis of
      treatment for atherosclerotic carotid stenosis with CEA and CAS performed at 5
      centers affiliated with the Vascular Study Group at public university hospitals
      in Brazil. The indications for the procedures will be determined by each
      surgeon's individual discretion, in accordance with preoperative risk evaluation.
      The primary outcome measures will be (1) any in-hospital stroke or death, and (2)
      any per-procedural stroke, death, or myocardial infarction (MI). Patients
      undergoing CEA in conjunction with cardiac surgery will be excluded from the
      study. Multivariate logistic regression will be performed to identify predictors
      of stroke or death in patients undergoing CEA and CAS. All tests of significance
      will be performed at the .05 level. This study was approved by the Committee of
      Ethics in Research at the University Hospital of Ribeirao Preto Medical School,
      and in all other participating institutions linked to National Research System
      and National Board of Health in Brazil (Process 15695/2011). RESULTS: This study
      is currently in the recruitment phase, and the final patient is expected to be
      enrolled by the end of 2018. We hope to recruit approximately 800 patients to the
      study. Analyses will focus on primary end points for patients that are allocated
      to each treatment group. During the per-procedural period, the occurrence of the
      primary end point components (stroke, MI, or death) for CAS and CEA will be
      analyzed for symptomatic or asymptomatic subjects. CONCLUSIONS: The analyses of
      the primary endpoints (and all others variables of the study) are expected to be
      published in 2019 in a peer reviewed journal, and results will be presented at
      scientific meetings, with summary results published online. This study will
      obtain new data related to the quality of treatment for carotid disease in Brazil
      at the primary training centers of future vascular surgeons, but the initial data
      that will be obtained and published (with the outcomes and complications) are
      restricted to the first 30 days postprocedure. This time restriction limits the
      comparison of the results that relate to the main goal of treatment, which is to
      decrease the risk of stroke over 5 years. The purpose of the study group is to
      continue the monitoring of patient records, and evaluate the follow-up data in
      the 5 years following the initial evaluation. This study protocol will contribute
      very significantly to improving the care of patients with carotid disease, in
      addition to qualifying the level of assistance provided in public university
      hospitals in the state of Sao Paulo, Brazil. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02538276;
      https://www.clinicaltrials.gov/ct2/show/NCT02538276 (Archived by WebCite at
      http://www.webcitation.org/6m7APnFLD).

PMID- 27881361
TI  - Older Veteran Digital Disparities: Examining the Potential for Solutions Within
      Social Networks.
AB  - BACKGROUND: Older adults typically have less access to the Internet than other
      age groups, and older Veterans may use the Internet even less due to economic and
      geographic reasons. OBJECTIVE: To explore solutions to this problem, our study
      examined older Veterans' reported ability to access technology through their
      close social ties. METHODS: Data were collected via mail survey from a sample of
      Veterans aged 65 years and older (N=266). RESULTS: Nearly half (44.0%, 117/266)
      of the sample reported having no Internet access. Yet, among those without
      current access, older Veterans reported having a median of 5 (IQR 7) close social
      ties with home Internet access. These older Veterans also reported that they
      would feel comfortable asking a median of 2 (IQR 4) social ties for help to
      access the Internet, and that a median of 2 (IQR 4) social ties would directly
      access the Internet for the older Veteran to help with health management.
      CONCLUSIONS: Findings suggest that even older Veterans without current Internet
      access have at least two social ties with home Internet who could be called upon
      for technology support. Thus, older Veterans may be willing to call upon these
      "surrogate seekers" for technology assistance and support in health management.
      This has implications for the digital divide, technology design, and health care
      policy.

PMID- 27881362
TI  - Should healthy people take a vitamin D supplement in winter months?

PMID- 27881364
TI  - Waheed Arian: Telemedicine pioneer.

PMID- 27881365
TI  - A musical about malignancy.

PMID- 27881366
TI  - What we know so far about the STPs.

PMID- 27881363
TI  - Association between prediabetes and risk of cardiovascular disease and all cause
      mortality: systematic review and meta-analysis.
AB  - OBJECTIVES:  To evaluate associations between different definitions of
      prediabetes and the risk of cardiovascular disease and all cause mortality.
      DESIGN:  Meta-analysis of prospective cohort studies. DATA SOURCES:  Electronic
      databases (PubMed, Embase, and Google Scholar). SELECTION CRITERIA:  Prospective
      cohort studies from general populations were included for meta-analysis if they
      reported adjusted relative risks with 95% confidence intervals for associations
      between the risk of composite cardiovascular disease, coronary heart disease,
      stroke, all cause mortality, and prediabetes. REVIEW METHODS:  Two authors
      independently reviewed and selected eligible studies, based on predetermined
      selection criteria. Prediabetes was defined as impaired fasting glucose according
      to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose
      5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L),
      impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L
      during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39
      47 mmol/mol : (5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%)
      according to the National Institute for Health and Care Excellence (NICE)
      guideline. The relative risks of all cause mortality and cardiovascular events
      were calculated and reported with 95% confidence intervals. RESULTS:  53
      prospective cohort studies with 1 611 339 individuals were included for analysis.
      The median follow-up duration was 9.5 years. Compared with normoglycaemia,
      prediabetes (impaired glucose tolerance or impaired fasting glucose according to
      IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite
      cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO,
      and impaired glucose tolerance, respectively), coronary heart disease (1.10,
      1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and
      all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39
      47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of
      composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart
      disease (1.15 and 1.28, respectively), but not with an increased risk of stroke
      and all cause mortality. CONCLUSIONS:  Prediabetes, defined as impaired glucose
      tolerance, impaired fasting glucose, or raised HbA1c, was associated with an
      increased risk of cardiovascular disease. The health risk might be increased in
      people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39
      mmol/mol.

PMID- 27881367
TI  - When is a point of view a conflict of interest?

PMID- 27881368
TI  - Where should the buck stop? Doctors taking the blame for system failure.

PMID- 27881369
TI  - NHS spent 8% more on medicines last year.

PMID- 27881370
TI  - Discussing and managing hematologic germ line variants.
AB  - With the introduction of genomic technologies, more hereditary cancer syndromes
      with hematologic malignancies are being described. Up to 10% of hematologic
      malignancies in children and adults may be the result of an underlying inherited
      genetic risk. Managing these patients with hereditary hematologic malignancies,
      including familial leukemia, remains a clinical challenge because there is little
      information about these relatively rare disorders. This article covers some of
      the issues related to the diagnosis and interpretation of variants associated
      with hereditary hematologic malignancies, including the importance of an accurate
      family history in interpreting genetic variants associated with disease. The
      challenges of screening other family members and offering the most appropriate
      early malignancy detection is also discussed. We now have a good opportunity to
      better define hereditary cancer syndromes with associated hematologic
      malignancies and contribute to clinically effective guidelines.

PMID- 27881371
TI  - Pure red cell aplasia.
AB  - Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic
      anemia with severe reticulocytopenia and marked reduction or absence of erythroid
      precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of
      PRCA. Acquired PRCA may be either a primary disorder or secondary to some other
      disorder or agent. Primary acquired PRCA is an autoimmune disorder that is
      frequently antibody-mediated. Myelodysplastic syndromes may also present with the
      morphologic appearance of PRCA. Secondary acquired PRCA may be associated with
      collagen vascular/autoimmune disorders such as systemic lupus erythematosus;
      lymphoproliferative disorders such as chronic lymphocytic leukemia or large
      granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma
      and other solid tumors; or a variety of other disorders, drugs, or toxic agents.
      The therapeutic approach to PRCA typically involves immunosuppression, but
      specific pathogenic subtypes are associated with specific therapeutic approaches.
      Cyclosporine A, with or without concurrent corticosteroids, appears to be the
      single most effective immunosuppressive agent.

PMID- 27881372
TI  - Should adults take vitamin D supplements to prevent disease?

PMID- 27881374
TI  - Integrating a novel concept of sentence optotypes into the RADNER Reading Charts.
AB  - PURPOSE: To add a new set of 24 sentence optotypes to the German version of the
      RADNER reading charts and to investigate whether sentences constructed based upon
      an optimised concept of sentence optotypes can be used together with the original
      38 sentences. METHODS: Twenty-eight optimised sentence optotypes were constructed
      based upon the concept of sentence optotypes as established for the RADNER
      Reading Charts, with words having the same number of characters and syllables
      being placed in the same positions. The best comparable sentences were
      statistically selected in 30 volunteers. Reading speed and the number of errors
      were determined. Validity was analysed in comparison to a 111-word long
      standardised paragraph and 7 of the 38 original sentence optotypes. RESULTS: The
      mean reading speed obtained with the 28 sentences was 192.30+/-26.69 words per
      minute (wpm), as compared with 192.47+/-25.32 wpm for the 7 original sentence
      optotypes and 165.28+/-20.82 wpm for the long paragraph; 24 of the 28 optimised
      sentences met our selection criteria for reading speed/time (mean reading speed:
      192.41+/-26.58). The mean number of reading errors was 0.10+/-0.30. The
      correlation between the 24 optimised sentence optotypes and the long paragraph
      was r=0.90. Reliability analyses yielded an overall Cronbach's alpha coefficient
      of 0.992. CONCLUSION: The 24 new sentence optotypes can be integrated into the
      existing set of 38 original sentences. Since all the statistical results obtained
      were similar to those of the original sentences, the best possible reliability
      had apparently already been achieved with the original sentence optotypes.

PMID- 27881375
TI  - A premenarcheal girl with urogenital bleeding.

PMID- 27881376
TI  - QUESTION 2: Is permissive hypercapnia beneficial to preterm infants?

PMID- 27881377
TI  - Oxygen saturation of children in Pakistan's high mountain pastoral communities.

PMID- 27881378
TI  - Cardiac arrest outcomes and the weekend effect.

PMID- 27881379
TI  - Art therapy with a child with pulmonary hypertension.

PMID- 27881380
TI  - Vulvar inflammation: a presentation of Crohn's disease.

PMID- 27881381
TI  - Two-Year Outcomes of a Randomized Trial Investigating a 6-Week Return to Full
      Weightbearing After Matrix-Induced Autologous Chondrocyte Implantation.
AB  - BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) has
      demonstrated encouraging outcomes in treating patients with knee cartilage
      defects. Postoperatively, the time required to attain full weightbearing (WB)
      remains conservative. HYPOTHESIS: We hypothesized that patients would have no
      significant clinical or radiological differences or graft complications after an
      8-week or 6-week return to full WB after MACI. STUDY DESIGN: Randomized
      controlled trial; Level of evidence, 1. METHODS: A total of 37 knees (n = 35
      patients) were randomly allocated to either an 8-week return to full WB that we
      considered current best practice based on the existing literature (CR group; n =
      19 knees) or an accelerated 6-week WB approach (AR group; n = 18 knees). Patients
      were evaluated preoperatively and at 1, 2, 3, 6, 12, and 24 months after surgery,
      using the Knee Injury and Osteoarthritis Outcome Score, 36-Item Short Form Health
      Survey, visual analog pain scale, 6-minute walk test, and active knee range of
      motion. Isokinetic dynamometry was used to assess peak knee extension and flexion
      strength and limb symmetry indices (LSIs) between the operated and nonoperated
      limbs. Magnetic resonance imaging (MRI) was undertaken to evaluate the quality
      and quantity of repair tissue as well as to calculate an MRI composite score.
      RESULTS: Significant improvements ( P < .05) were observed in all subjective
      scores, active knee flexion and extension, 6-minute capacity, peak knee extensor
      torque in the operated limb, and knee extensor LSI, although no group differences
      existed. Although knee flexor LSIs were above 100% for both groups at 12 and 24
      months after surgery, LSIs for knee extensor torque at 24 months were 93.7% and
      87.5% for the AR and CR groups, respectively. The MRI composite score and
      pertinent graft parameters significantly improved over time ( P < .05), with some
      superior in the AR group at 24 months. All patients in the AR group (100%)
      demonstrated good to excellent infill at 24 months, compared with 83% of patients
      in the CR group. Two cases of graft failure were observed, both in the CR group.
      At 24 months, 83% of patients in the CR group and 88% in the AR group were
      satisfied with the results of their MACI surgery. CONCLUSION: Patients in the AR
      group who reduced the length of time spent ambulating on crutches produced
      comparable outcomes up to 24 months, without compromising graft integrity.

PMID- 27881383
TI  - Clinical and Radiological Outcomes After Hamstring Anterior Cruciate Ligament
      Reconstructions: Comparison Between Fixed-Loop and Adjustable-Loop Cortical
      Suspension Devices.
AB  - BACKGROUND: Few studies have compared clinical and radiological outcomes after
      hamstring anterior cruciate ligament (ACL) reconstruction with fixed-loop and
      adjustable-loop cortical suspension devices. Purpose/Hypothesis: The purpose of
      this retrospective study was to compare clinical outcomes and tunnel widening
      after hamstring ACL reconstructions with fixed- and adjustable-loop cortical
      suspension devices. The hypothesis was that compared with femoral graft fixation
      with the fixed-loop device, fixation with the adjustable-loop device would show
      similar clinical outcomes and would result in less tunnel widening after
      hamstring ACL reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: A total of 117 consecutive patients underwent hamstring ACL
      reconstruction at a single institution. The fixed-loop cortical suspension device
      was used in 67 patients, and the adjustable-loop cortical suspension device was
      used in 50 patients. All patients were observed for a minimum of 2 years.
      Postoperative knee laxity was evaluated with the Lachman test, pivot-shift test,
      and KT-1000 arthrometer. Functional evaluations were performed by use of the
      Lysholm score and the Tegner activity scale. On anteroposterior (AP) and lateral
      radiographs, the measured diameters of the femoral tunnel at 1 year after surgery
      were compared with the diameter of the reamer used at surgery. The measured
      diameters of the tibial tunnel at 1 year after surgery were compared with those
      taken immediately after surgery. RESULTS: The mean KT-1000 arthrometer laxity
      measurement was 1.5 +/- 1.8 mm in the fixed-loop group and 1.2 +/- 2.3 mm in the
      adjustable-loop group ( P = .530). Results of postoperative knee laxity
      evaluations and functional outcomes from both groups showed no statistically
      significant differences. However, the fixed-loop group showed significantly
      better stability in the pivot-shift test than did the adjustable-loop group ( P =
      .018). On AP radiographs, the mean diameter of the femoral and tibial tunnels
      increased by 42.2% +/- 15.9% and 37.0% +/- 17.8%, respectively, in the fixed-loop
      group and by 43.0% +/- 15.4% and 36.8% +/- 18.2% in the adjustable-loop group. On
      lateral radiographs, the mean diameter of the femoral and tibial tunnels
      increased by 38.1% +/- 14.8% and 39.9% +/- 13.8%, respectively, in the fixed-loop
      group and by 35.8% +/- 12.2% and 38.1% +/- 21.0% in the adjustable-loop group. No
      significant differences were found between the 2 groups in postoperative femoral
      and tibial tunnel widening on AP radiographs ( P = .801 and .951, respectively)
      or lateral radiographs ( P = .422 and .621, respectively). CONCLUSION: Compared
      with femoral fixation by use of the fixed-loop device, femoral fixation by use of
      the adjustable-loop device showed similar clinical outcomes but did not reduce
      tunnel widening after hamstring ACL reconstructions.

PMID- 27881382
TI  - Early Changes in Knee Center of Rotation During Walking After Anterior Cruciate
      Ligament Reconstruction Correlate With Later Changes in Patient-Reported
      Outcomes.
AB  - BACKGROUND: Altered knee kinematics after anterior cruciate ligament injury and
      reconstruction (ACLR) have been implicated in the development of posttraumatic
      osteoarthritis (PTOA), leading to poor long-term clinical outcomes. PURPOSE: This
      study was conducted to determine (1) whether the average knee center of rotation
      (KCOR), a multidimensional metric of knee kinematics, of the ACL-reconstructed
      knee during walking differs from that of the uninjured contralateral knee; (2)
      whether KCOR changes between 2 and 4 years after surgery; and (3) whether early
      KCOR changes predict patient-reported outcomes 8 years after ACLR. STUDY DESIGN:
      Descriptive laboratory study. METHODS: Twenty-six human participants underwent
      gait analysis with calculation of bilateral KCOR during walking at 2 and 4 years
      after unilateral ACLR. Knee injury and Osteoarthritis Outcome Score (KOOS) and
      Lysholm score results were collected at 2, 4, and 8 years after ACLR in 13 of
      these participants. RESULTS: The ACL-reconstructed knee showed greater medial
      compartment motion because of pivoting about a more lateral KCOR ( P = .03) than
      the contralateral knee at 2 years. KCOR became less lateral over time ( P =
      .047), with values approaching those of the uninjured knee by 4 years ( P = .55).
      KCOR was also more anterior in the ACL-reconstructed knee at 2 years ( P = .02).
      Between 2 and 4 years, KCOR moved posteriorly in 16 (62%) and anteriorly in 10
      (38%) participants. Increasing the anterior position of KCOR in the ACL
      reconstructed knee from 2 to 4 years correlated with worsening clinical outcomes
      at 4 years (KOOS-Quality of Life, R2 = 0.172) and more strongly at 8 years
      (Lysholm score, R2 = 0.41; KOOS-Pain, R2 = 0.37; KOOS-Symptoms, R2 = 0.58; and
      KOOS-Quality of Life, R2 = 0.50). CONCLUSION: The observed changes to KCOR during
      walking between 2 and 4 years after ACLR show progressive improvement toward
      kinematic symmetry over the 2-year follow-up. The correlation between
      increasingly abnormal kinematics and worsening clinical outcomes years later in a
      subset of participants provides a potential explanation for the incidence of PTOA
      after ACLR.

PMID- 27881384
TI  - Excess Stress Fractures, Musculoskeletal Injuries, and Health Care Utilization
      Among Unfit and Overweight Female Army Trainees.
AB  - BACKGROUND: Musculoskeletal injuries are prevalent among military trainees and
      certain occupations. Fitness and body mass index (BMI) have been associated with
      musculoskeletal conditions, including stress fractures. HYPOTHESIS: The incidence
      of, and excess health care utilization for, stress fracture and non-stress
      fracture overuse musculoskeletal injuries during the first 6 months of service is
      higher among unfit female recruits. Those who exceeded body fat limits are at a
      greater risk of incident stress fractures, injuries, or health care utilization
      compared with weight-qualified recruits. STUDY DESIGN: Cohort study; Level of
      evidence, 3. METHODS: All applicants to the United States Army were required to
      take a preaccession fitness test during the study period (February 2005-September
      2006). The test included a 5-minute step test scored as pass or fail. BMI was
      recorded at application. There were 2 distinct comparisons made in this study:
      (1) between weight-qualified physically fit and unfit women and (2) between
      weight-qualified physically fit women and those who exceeded body fat limits. We
      compared the incidence of, and excess health care utilization for,
      musculoskeletal injuries, including stress fractures and physical therapy visits,
      during the first 183 days of military service. RESULTS: Among the weight
      qualified women, unfit participants had a higher non-stress fracture injury
      incidence and related excess health care utilization rate compared with fit
      women, with rate ratios of 1.32 (95% CI, 1.14-1.53) and 1.18 (95% CI, 1.10-1.27),
      respectively. Among fit women, compared with the weight-qualified participants,
      those exceeding body fat limits had higher rate ratios for non-stress fracture
      injury incidence and related excess health care utilization of 1.27 (95% CI, 1.07
      1.50) and 1.20 (95% CI, 1.11-1.31), respectively. Weight-qualified women who were
      unfit had a higher incidence of stress fractures and related excess health care
      utilization compared with fit women, with rate ratios of 1.62 (95% CI, 1.19-2.21)
      and 1.22 (95% CI, 1.10-1.36), respectively. Among fit women exceeding body fat
      limits, the stress fracture incidence and related excess health care utilization
      rate ratios were 0.79 (95% CI, 0.49-1.28) and 1.44 (95% CI, 1.20-1.72),
      respectively, compared with those who were weight qualified. CONCLUSION: The
      results indicate a significantly increased risk of musculoskeletal injuries,
      including stress fractures, among unfit recruits and an increased risk of non
      stress fracture musculoskeletal injuries among recruits who exceeded body fat
      limits. Once injured, female recruits who were weight qualified but unfit and
      those who were fit but exceeded body fat limits had increased health care
      utilization. These findings may have implications for military accession and
      training policies as downsizing of military services will make it more important
      than ever to optimize the health and performance of individual service members.

PMID- 27881385
TI  - Antihypertensive effects of peroxisome proliferator-activated receptor-beta/delta
      activation.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of ligand-activated transcription factors, which is
      composed of three members encoded by distinct genes: PPARalpha, PPARbeta/delta,
      and PPARgamma. The biological actions of PPARalpha and PPARgamma and their
      potential as a cardiovascular therapeutic target have been extensively reviewed,
      whereas the biological actions of PPARbeta/delta and its effectiveness as a
      therapeutic target in the treatment of hypertension remain less investigated.
      Preclinical studies suggest that pharmacological PPARbeta/delta activation
      induces antihypertensive effects in direct [spontaneously hypertensive rat (SHR),
      ANG II, and DOCA-salt] and indirect (dyslipemic and gestational) models of
      hypertension, associated with end-organ damage protection. This review summarizes
      mechanistic insights into the antihypertensive effects of PPARbeta/delta
      activators, including molecular and functional mechanisms. Pharmacological
      PPARbeta/delta activation induces genomic actions including the increase of
      regulators of G protein-coupled signaling (RGS), acute nongenomic vasodilator
      effects, as well as the ability to improve the endothelial dysfunction, reduce
      vascular inflammation, vasoconstrictor responses, and sympathetic outflow from
      central nervous system. Evidence from clinical trials is also examined. These
      preclinical and clinical outcomes of PPARbeta/delta ligands may provide a basis
      for the development of therapies in combating hypertension.

PMID- 27881386
TI  - PPARalpha augments heart function and cardiac fatty acid oxidation in early
      experimental polymicrobial sepsis.
AB  - : Children with sepsis and multisystem organ failure have downregulated leukocyte
      gene expression of peroxisome proliferator-activated receptor-alpha (PPARalpha),
      a nuclear hormone receptor transcription factor that regulates inflammation and
      lipid metabolism. Mouse models of sepsis have likewise demonstrated that the
      absence of PPARalpha is associated with decreased survival and organ injury,
      specifically of the heart. Using a clinically relevant mouse model of early
      sepsis, we found that heart function increases in wild-type (WT) mice over the
      first 24 h of sepsis, but that mice lacking PPARalpha (Ppara-/-) cannot sustain
      the elevated heart function necessary to compensate for sepsis pathophysiology.
      Left ventricular shortening fraction, measured 24 h after initiation of sepsis by
      echocardiography, was higher in WT mice than in Ppara-/- mice. Ex vivo working
      heart studies demonstrated greater developed pressure, contractility, and aortic
      outflow in WT compared with Ppara-/- mice. Furthermore, cardiac fatty acid
      oxidation was increased in WT but not in Ppara-/- mice. Regulatory pathways
      controlling pyruvate incorporation into the citric acid cycle were inhibited by
      sepsis in both genotypes, but the regulatory state of enzymes controlling fatty
      acid oxidation appeared to be permissive in WT mice only. Mitochondrial
      ultrastructure was not altered in either genotype indicating that severe
      mitochondrial dysfunction is unlikely at this stage of sepsis. These data suggest
      that PPARalpha expression supports the hyperdynamic cardiac response early in the
      course of sepsis and that increased fatty acid oxidation may prevent morbidity
      and mortality. NEW & NOTEWORTHY: In contrast to previous studies in septic shock
      using experimental mouse models, we are the first to demonstrate that heart
      function increases early in sepsis with an associated augmentation of cardiac
      fatty acid oxidation. Absence of peroxisome proliferator-activated receptor-alpha
      (PPARalpha) results in reduced cardiac performance and fatty acid oxidation in
      sepsis.

PMID- 27881387
TI  - Intrauterine growth restriction influences vascular remodeling and stiffening in
      the weanling rat more than sex or diet.
AB  - : Intrauterine growth restriction (IUGR) increases the incidence of adult
      cardiovascular disease (CVD). The sex-specific developmental mechanisms for IUGR
      induced and Western high-fat diet (HFD) modification of CVD remain poorly
      understood. We hypothesized a maternal HFD in the Sprague-Dawley rat would
      augment IUGR-induced CVD in the offspring through decreased cardiac function and
      increased extracellular matrix (ECM) remodeling and stiffness in a sex-specific
      manner. HFD or regular diet (Reg) was given from 5 wk before mating through
      postnatal day (PND) 21. IUGR was induced by uterine artery ligation at embryonic
      day 19.5 (term = 21.5 days). At PND 21, echocardiographic assessments were made
      and carotid arteries tested for vascular compliance using pressure myography.
      Arterial samples were quantified for ECM constituents or fixed for histologic
      evaluation. The insult of IUGR (IUGR + Reg and IUGR + HFD) led to increased
      mechanical stiffness in both sexes (P < 0.05). The combination of IUGR + HFD
      increased diastolic blood pressure 47% in males (M) and 35% in females (F)
      compared with the Con + Reg (P < 0.05). ECM remodeling in IUGR + HFD caused fewer
      (M = -29%, F = -24%) but thicker elastin bands (M = 18%, F = 18%) and increased
      total collagen (M = 49%, F = 34%) compared with Con + Reg arteries. Remodeling in
      IUGR + HFD males increased medial collagen and soluble collagen (P < 0.05).
      Remodeling in IUGR + HFD females increased adventitial collagen and wall
      thickness (P < 0.05) and decreased matrix metalloproteinase 2 (MMP-2), advanced
      glycosylation end products (AGE), and receptor AGE (RAGE; P < 0.05). In summary,
      both IUGR + Reg and IUGR + HFD remodel ECM in PND 21 rats. While IUGR + HFD
      increases blood pressure, IUGR but not HFD increases vascular stiffness
      suggesting a specific mechanism of vascular remodeling that can be targeted to
      limit future disease. NEW & NOTEWORTHY: We report intrauterine growth restriction
      (IUGR) increases vascular stiffening in both male and female rats through
      increased collagen content and altered elastin structure more than a high-fat
      diet (HFD) alone. Our study shows the importance of stiffness supporting the
      hypothesis that there are physiologic differences and potential windows for early
      intervention targeting vascular remodeling mechanisms.

PMID- 27881388
TI  - Hyperglycemia induces defective Ca2+ homeostasis in cardiomyocytes.
AB  - : Diabetes and other metabolic conditions characterized by elevated blood glucose
      constitute important risk factors for cardiovascular disease. Hyperglycemia
      targets myocardial cells rendering ineffective mechanical properties of the
      heart, but cellular alterations dictating the progressive deterioration of
      cardiac function with metabolic disorders remain to be clarified. In the current
      study, we examined the effects of hyperglycemia on cardiac function and myocyte
      physiology by employing mice with high blood glucose induced by administration of
      streptozotocin, a compound toxic to insulin-producing beta-cells. We found that
      hyperglycemia initially delayed the electrical recovery of the heart, whereas
      cardiac function became defective only after ~2 mo with this condition and
      gradually worsened with time. Prolonged hyperglycemia was associated with
      increased chamber dilation, thinning of the left ventricle (LV), and myocyte
      loss. Cardiomyocytes from hyperglycemic mice exhibited defective Ca2+ transients
      before the appearance of LV systolic defects. Alterations in Ca2+ transients
      involved enhanced spontaneous Ca2+ releases from the sarcoplasmic reticulum (SR),
      reduced cytoplasmic Ca2+ clearance, and declined SR Ca2+ load. These defects have
      important consequences on myocyte contraction, relaxation, and mechanisms of rate
      adaptation. Collectively, our data indicate that hyperglycemia alters
      intracellular Ca2+ homeostasis in cardiomyocytes, hindering contractile activity
      and contributing to the manifestation of the diabetic cardiomyopathy. NEW &
      NOTEWORTHY: We have investigated the effects of hyperglycemia on cardiomyocyte
      physiology and ventricular function. Our results indicate that defective Ca2+
      handling is a critical component of the progressive deterioration of cardiac
      performance of the diabetic heart.

PMID- 27881390
TI  - Dietary quality of the US child and adolescent population: trends from 1999 to
      2012 and associations with the use of federal nutrition assistance programs.
AB  - BACKGROUND: The state of the economy, changes in federal food assistance
      programs, and policies related to nutrition and the food supply in the United
      States may influence dietary quality in children and adolescents. OBJECTIVE: We
      investigated dietary quality trends from 1999 to 2012 in the US child and
      adolescent population and their associations with socioeconomic status and
      participation in federal food assistance programs. DESIGN: In this study, a
      nationally representative sample of 38,487 children and adolescents, aged 2-18 y,
      in the NHANES from 1999 to 2012 were included. Dietary information was collected
      with the use of a 24-h dietary recall. Dietary quality was measured with the use
      of the Healthy Eating Index 2010 (HEI-2010). RESULTS: The mean HEI-2010 increased
      significantly from 42.5 (95% CI: 41.2, 43.8) to 50.9 (95% CI: 50.0, 51.8) from
      1999 to 2012 (P-linear trend < 0.001). The reduction in empty calorie intake
      contributed to greater than one-third of this improvement in the total HEI-2010.
      We also observed significant increases in 9 other HEI-2010 component scores.
      However, the HEI-2010 component score for sodium decreased significantly, which
      reflected an increase in sodium consumption. We calculated the covariate-adjusted
      mean HEI-2010 score in subgroups that were defined by sociodemographic status and
      participation in nutrition assistance program at each NHANES cycle. Non-Hispanic
      black children and adolescents had a consistently lower HEI-2010 than that of
      other groups across all NHANES cycles. We observed a trend toward a lower HEI
      2010 in Supplemental Nutrition Assistance Program (SNAP) participants than in
      nonparticipants after the 2003-2004 cycle. We also observed a lower HEI-2010 in
      participants in the National School Lunch Program (NSLP) and the School Breakfast
      Program (SBP) than in nonparticipants. In general, participants in the Special
      Supplemental Nutrition Program for Women, Infants, and Children appeared to have
      a higher HEI-2010 than that of nonparticipants. CONCLUSIONS: Although HEI-2010
      scores in children and adolescents improved steadily, the overall dietary quality
      remained poor. Participants in the SNAP and participants in the National School
      Lunch Program, School Breakfast Program, or both have lower dietary quality than
      do nonparticipants. Future policy interventions are needed to continue
      improvement in dietary quality and to address disparities.

PMID- 27881389
TI  - Changes in skeletal muscle and organ size after a weight-loss intervention in
      overweight and obese type 2 diabetic patients.
AB  - BACKGROUND: The effect of a weight-loss intervention on the masses of lean
      tissues and organs in humans is not well known. OBJECTIVE: We studied the effects
      of a diet and exercise weight-loss intervention on skeletal muscle (SM) mass and
      selected organs over 2 y using MRI in overweight adults with type 2 diabetes.
      DESIGN: Participants were 53 women and 39 men [mean +/- SD: age 58 +/- 7 y; body
      mass index (BMI; in kg/m2) 32 +/- 3] enrolled in the Look AHEAD (Action for
      Health in Diabetes) trial and randomly assigned to an intensive lifestyle
      intervention (ILI) or diabetes support and education (DSE) on whom 2 y of data
      were collected. MRI-derived measurements of SM, heart, liver, kidney, spleen, and
      pancreas were acquired. RESULTS: Adjusted for baseline weight, height, age, sex,
      and ethnicity, the ILI group weighed (mean +/- SE) 6.6 +/- 0.7 kg less after 1 y
      and 5.2 +/- 0.7 kg less after 2 y, whereas the DSE group did not change
      significantly (-0.4 +/- 0.6 and -1.0 +/- 0.7 kg after 1 and 2 y, respectively; P
      interaction < 0.001). Total SM decreased in both groups during year 1 (-1.4 +/-
      0.2 kg; P < 0.001) with appendicular SM regained during year 2. Liver and spleen
      masses decreased in the ILI group (-0.12 +/- 0.02 and -0.006 +/- 0.003 kg,
      respectively) but were unchanged in the DSE group (0.00 +/- 0.02 and 0.004 +/-
      0.003 kg, respectively). Kidney mass decreased by 0.013 +/- 0.003 kg (P < 0.001)
      over 2 y in both groups. CONCLUSIONS: Decreases in liver (in Caucasians but not
      African Americans) and spleen were detected after a 6.2-kg weight reduction
      compared with a control group. SM and kidney mass decreased in both groups.
      Appendicular SM was regained during the second year whereas trunk SM was not. No
      evidence of a disproportionate loss of high-metabolic rate organs (heart, liver,
      kidney, spleen) compared with SM was found.

PMID- 27881392
TI  - Higher serum phenylalanine concentration is associated with more rapid telomere
      shortening in men.
AB  - BACKGROUND: Telomere length and telomere shortening are associated with age
      related health outcomes. Only a few studies have been able to longitudinally
      report on factors that are associated with changes in telomere length in an aging
      population. OBJECTIVE: We studied the longitudinal relation between telomere
      length, the change in telomere length, and circulating amino acids. DESIGN: A
      total of 812 subjects from the Helsinki Birth Cohort Study (born from 1934 to
      1944), who underwent 3 clinical visits during a 10-y interval that included
      measurements of cardiometabolic risk factors, were included in the study.
      Leukocyte telomere length (LTL) was measured with the use of quantitative real
      time polymerase chain reaction. Circulating branched-chain and aromatic amino
      acids (alanine, glycine, histidine, phenylalanine, leucine, isoleucine, valine,
      and tyrosine) were assessed with the use of high-throughput nuclear magnetic
      resonance spectroscopy. RESULTS: The relative +/- SD LTL at a mean age of 71 y
      was 0.79 +/- 0.27 in men and 0.89 +/- 0.35 in women (P < 0.001). Of the studied
      amino acids, the strongest inverse association was observed between the
      phenylalanine concentration that was measured 5 y earlier and the LTL. This
      finding was significant in men (P = 0.021) and remained significant after
      adjustment for multiple comparisons, but it was not significant in women (P =
      0.39). Longitudinally, the change in LTL over 10 y was inversely associated with
      the phenylalanine concentration in men (P = 0.007) but not in women (P = 0.58)
      after adjustment for baseline LTL, age, smoking, and percentage of body fat.
      CONCLUSIONS: The serum phenylalanine concentration is associated with telomere
      length and, therefore, potentially with the aging process. Because the
      associations reported are observational, no conclusions can be made regarding
      causality. Our findings support the hypothesis that cellular pathways that
      regulate aging are sex specific.

PMID- 27881391
TI  - The role of metabolism (and the microbiome) in defining the clinical efficacy of
      dietary flavonoids.
AB  - At a population level, there is growing evidence of the beneficial effects of
      dietary flavonoids on health. However, there is extensive heterogeneity in the
      response to increased intake, which is likely mediated via wide interindividual
      variability in flavonoid absorption and metabolism. Flavonoids are extensively
      metabolized by phase I and phase II metabolism (which occur predominantly in the
      gastrointestinal tract and liver) and colonic microbial metabolism. A number of
      factors, including age, sex, and genotype, may affect these metabolic processes.
      In addition, food composition and flavonoid source are likely to affect
      bioavailability, and emerging data suggest a critical role for the microbiome.
      This review will focus on the current knowledge for the main subclasses of
      flavonoids, including anthocyanins, flavonols, flavan-3-ols, and flavanones, for
      which there is growing evidence from prospective studies of beneficial effects on
      health. The identification of key factors that govern metabolism and an
      understanding of how the differential capacity to metabolize these bioactive
      compounds affect health outcomes will help establish how to optimize intakes of
      flavonoids for health benefits and in specific subgroups. We identify research
      areas that need to be addressed to further understand important determinants of
      flavonoid bioavailability and metabolism and to advance the knowledge base that
      is required to move toward the development of dietary guidelines and
      recommendations for flavonoids and flavonoid-rich foods.

PMID- 27881393
TI  - Food portion size and energy density evoke different patterns of brain activation
      in children.
AB  - BACKGROUND: Large portions of food promote intake, but the mechanisms that drive
      this effect are unclear. Previous neuroimaging studies have identified the brain
      reward and decision-making systems that are involved in the response to the
      energy density (ED) (kilocalories per gram) of foods, but few studies have
      examined the brain response to the food portion size (PS). OBJECTIVE: We used
      functional MRI (fMRI) to determine the brain response to food images that
      differed in PSs (large and small) and ED (high and low). DESIGN: Block-design
      fMRI was used to assess the blood oxygen level-dependent (BOLD) response to
      images in 36 children (7-10 y old; girls: 50%), which was tested after a 2-h
      fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole
      brain cluster-corrected analysis was used to compare BOLD activation for main
      effects of the PS, ED, and their interaction. Secondary analyses were used to
      associate BOLD contrast values with appetitive traits and laboratory intake from
      meals for which the portions of all foods were increased. RESULTS: Compared with
      small-PS cues, large-PS cues were associated with decreased activation in the
      inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were
      associated with increased activation in multiple regions (e.g., in the caudate,
      cingulate, and precentral gyrus) and decreased activation in the insula and
      superior temporal gyrus (P < 0.01 for all). A PS * ED interaction was shown in
      the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues
      compared with low-ED cues in the insula, declive, and precentral gyrus were
      negatively related to appetitive traits (P < 0.05). There were no associations
      between the brain response to the PS and either appetitive traits or intake.
      CONCLUSIONS: Cues regarding food PS may be processed in the lateral prefrontal
      cortex, which is a region that is implicated in cognitive control, whereas ED
      activates multiple areas involved in sensory and reward processing. Possible
      implications include the development of interventions that target decision-making
      and reward systems differently to moderate overeating.

PMID- 27881394
TI  - Total red meat intake of >=0.5 servings/d does not negatively influence
      cardiovascular disease risk factors: a systemically searched meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Observational associations between red meat intake and cardiovascular
      disease (CVD) are inconsistent. There are limited comprehensive analyses of
      randomized controlled trials (RCTs) that investigate the effects of red meat
      consumption on CVD risk factors. OBJECTIVE: The purpose of this systematically
      searched meta-analysis was to assess the effects of consuming >=0.5 or <0.5
      servings of total red meat/d on CVD risk factors [blood total cholesterol (TC),
      LDL cholesterol, HDL cholesterol, triglycerides, ratio of TC to HDL cholesterol
      (TC:HDL), and systolic and diastolic blood pressures (SBP and DBP,
      respectively)]. We hypothesized that the consumption of >=0.5 servings of total
      red meat/d would have a negative effect on these CVD risk factors. DESIGN: Two
      researchers independently screened 945 studies from PubMed, Cochrane Library, and
      Scopus databases and extracted data from 24 qualified RCTs. Inclusion criteria
      were 1) RCT, 2) subjects aged >=19 y, 3) consumption of >=0.5 or <0.5 total red
      meat servings/d [35 g (1.25 ounces)], and 4) reporting >=1 CVD risk factor. We
      performed an adjusted 2-factor nested ANOVA mixed-effects model procedure on the
      postintervention values of TC, LDL cholesterol, HDL cholesterol, TC:HDL
      cholesterol, triglycerides, SBP, and DBP; calculated overall effect sizes of
      change values; and used a repeated-measures ANOVA to assess pre- to
      postintervention changes. RESULTS: Red meat intake did not affect lipid
      lipoprotein profiles or blood pressure values postintervention (P > 0.05) or
      changes over time [weighted mean difference (95% CI): -0.01 mmol/L (-0.08, 0.06
      mmol/L), 0.02 mmol/L (-0.05, 0.08 mmol/L), 0.03 mmol/L (-0.01, 0.07 mmol/L), and
      0.04 mmol/L (-0.02, 0.10 mmol/L); -0.08 mm Hg (-0.26, 0.11 mm Hg); and -1.0 mm Hg
      (-2.4, 0.78 mm Hg) and 0.1 mm Hg (-1.2, 1.5 mm Hg) for TC, LDL cholesterol, HDL
      cholesterol, triglycerides, TC:HDL cholesterol, SBP, and DBP, respectively].
      Among all subjects, TC, LDL cholesterol, HDL cholesterol, TC:HDL cholesterol,
      triglycerides, and DBP, but not SBP, decreased over time (P < 0.05). CONCLUSIONS:
      The results from this systematically searched meta-analysis of RCTs support the
      idea that the consumption of >=0.5 servings of total red meat/d does not
      influence blood lipids and lipoproteins or blood pressures.

PMID- 27881395
TI  - Diet-induced weight loss improves not only cardiometabolic risk markers but also
      markers of vascular function: a randomized controlled trial in abdominally obese
      men.
AB  - BACKGROUND: Many trials assessing effects of dietary weight loss on vascular
      function have been performed without no-weight loss control groups and in
      individuals with obesity-related morbidities. Usually a limited set of vascular
      function markers has been investigated. OBJECTIVE: The objective of this study
      was to examine effects of diet-induced weight loss on various vascular function
      markers and differences between normal-weight and abdominally obese men at
      baseline and after weight reduction. DESIGN: Twenty-five healthy, normal-weight
      men (waist circumference: <94 cm) and 54 abdominally obese men (waist
      circumference: 102-110 cm) participated. Abdominally obese participants were
      randomly allocated to a dietary weight-loss or a no-weight loss control group.
      Individuals from the weight-loss group followed a calorie-restricted diet for 6
      wk to obtain a waist circumference <102 cm followed by a weight-maintenance
      period of 2 wk. The control group maintained their habitual diet and physical
      activity levels. The primary outcome was the change in brachial artery flow
      mediated vasodilation (FMD). RESULTS: Compared with the control group, FMD did
      not change in the weight-loss group, but carotid-to-femoral pulse wave velocity
      tended to decrease by 0.5 m/s (P = 0.065). The retinal arteriolar caliber
      increased by 5 MUm (P < 0.001) and the arteriolar-to-venular ratio by 0.02 (P <
      0.01). Soluble endothelial selectin and soluble intercellular adhesion molecule
      concentrations decreased (P < 0.001). Also, total cholesterol, low-density
      lipoprotein cholesterol, triacylglycerol, glucose, insulin, C-peptide,
      homeostasis model assessment of insulin resistance, and blood pressure improved
      (P < 0.05 for all variables). Except for FMD, these markers differed at baseline
      between normal-weight and abdominally obese men but became comparable after
      weight loss. CONCLUSIONS: In abdominally obese men, dietary weight loss targeting
      a waist circumference of <102 cm improved retinal microvascular caliber, plasma
      biomarkers of microvascular endothelial function, and the more conventional
      cardiometabolic risk markers. Aortic stiffness tended to decrease, but FMD was
      not changed. This trial was registered at clinicaltrials.gov as NCT01675401.

PMID- 27881396
TI  - Involvement of infiltrating macrophage-derived activin A in the progression of
      renal damage in MRL-lpr mice.
AB  - Lupus nephritis is a life-threatening complication of systemic lupus
      erythematosus (SLE). Various growth factors, cytokines, and chemokines are
      implicated in the development of SLE. However, the pathophysiological processes
      involved in the development of lupus nephritis still remain unclear. In this
      study, we examined the involvement of activin A, a member of the transforming
      growth factor beta (TGF-beta) superfamily, in the progression of renal damage in
      lupus-prone MRL-lpr mice. Activin A was not expressed in the kidneys of control
      MRL-MpJ mice but was detectable in perivascular infiltrating cluster of
      differentiation 68 (CD68)-positive cells in the kidneys of MRL-lpr mice. Urinary
      activin A, which was also absent in MRL-MpJ mice, was detectable in MRL-lpr mice
      from 16 wk onward. Urinary activin A levels were significantly correlated with
      the number of perivascular inflammatory cell layers, the number of crescentic
      glomeruli, and the percentage of Elastica van Gieson (EVG)-positive fibrotic
      areas, but not with urinary protein levels or serum activin A. When activin
      action was blocked in vivo by the intraperitoneal administration of an activin
      antagonist, follistatin, the number of crescentic glomeruli, percentage of EVG
      positive fibrotic areas, CD68-positive cell infiltration, and proteinuria were
      significantly reduced in a dose-dependent manner. These data suggest that
      infiltrating macrophage-derived activin A is involved in the progression of renal
      damage in MRL-lpr mice.

PMID- 27881397
TI  - A simple method to ensure homogeneous drug distribution during intrarenal
      infusion.
AB  - Intrarenal drug infusion plays an important role in renal experimental research.
      Laminar flow of the blood can cause streaming and inhomogeneous intrarenal
      distribution of infused drugs. We suggest a simple method to achieve a
      homogeneous intravascular distribution of drugs infused into the renal artery of
      anesthetized rats. The method employs a multiple sidehole catheter inserted into
      the renal artery, which enables an efficient drug mixing with the arterial blood.
      To verify the efficiency of this method, we use laser speckle imaging and renal
      artery flowmetry. The results show that, compared with the conventional single
      hole catheter, the multiple sidehole catheter provides a more uniform drug
      distribution and a homogenous vascular response on the surface of the kidney.

PMID- 27881398
TI  - Separate and shared sympathetic outflow to white and brown fat coordinately
      regulates thermoregulation and beige adipocyte recruitment.
AB  - White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and
      regulated by the sympathetic nervous system (SNS). It is not clear, however,
      whether there are shared or separate central SNS outflows to WAT and BAT that
      regulate their function. We injected two isogenic strains of pseudorabies virus,
      a retrograde transneuronal viral tract tracer, with unique fluorescent reporters
      into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian
      hamsters to define SNS pathways to both. To test the functional importance of SNS
      coordinated control of BAT and WAT, we exposed hamsters with denervated SNS
      nerves to IBAT to 4 degrees C for 16-24 h and measured core and fat temperatures
      and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in
      fat tissues. Overall, there were more SNS neurons innervating IBAT than IWAT
      across the neuroaxis. However, there was a greater percentage of singly labeled
      IWAT neurons in midbrain reticular nuclei than singly labeled IBAT neurons. The
      hindbrain had ~30-40% of doubly labeled neurons while the forebrain had ~25%
      suggesting shared SNS circuitry to BAT and WAT across the brain. The raphe
      nucleus, a key region in thermoregulation, had ~40% doubly labeled neurons.
      Hamsters with IBAT SNS denervation maintained core body temperature during acute
      cold challenge and had increased beige adipocyte formation in IWAT. They also had
      increased IWAT NETO, temperature, and UCP1 expression compared with intact
      hamsters. These data provide strong neuroanatomical and functional evidence of
      WAT and BAT SNS cross talk for thermoregulation and beige adipocyte formation.

PMID- 27881399
TI  - Intradermal administration of endothelin-1 attenuates endothelium-dependent and 
      independent cutaneous vasodilation via Rho kinase in young adults.
AB  - We recently showed that intradermal administration of endothelin-1 diminished
      endothelium-dependent and -independent cutaneous vasodilation. We evaluated the
      hypothesis that Rho kinase may be a mediator of this response. We also sought to
      evaluate if endothelin-1 increases sweating. In 12 adults (25 +/- 6 yr), we
      measured cutaneous vascular conductance (CVC) and sweating during 1) endothelium
      dependent vasodilation induced via administration of incremental doses of
      methacholine (0.25, 5, 100, and 2,000 mM each for 25 min) and 2) endothelium
      independent vasodilation induced via administration of 50 mM sodium nitroprusside
      (20-25 min). Responses were evaluated at four skin sites treated with either 1)
      lactated Ringer solution (Control), 2) 400 nM endothelin-1, 3) 3 mM HA-1077 (Rho
      kinase inhibitor), or 4) endothelin-1+HA-1077. Pharmacological agents were
      intradermally administered via microdialysis. Relative to the Control site,
      endothelin-1 attenuated endothelium-dependent vasodilation (CVC at 2,000 mM
      methacholine, 80 +/- 10 vs. 56 +/- 15%max, P < 0.01); however, this response was
      not detected when the Rho kinase inhibitor was simultaneously administered (CVC
      at 2,000 mM methacholine for Rho kinase inhibitor vs. endothelin-1 + Rho kinase
      inhibitor sites: 73 +/- 9 vs. 72 +/- 11%max, P > 0.05). Endothelium-independent
      vasodilation was attenuated by endothelin-1 compared with the Control site (CVC,
      92 +/- 13 vs. 70 +/- 14%max, P < 0.01). However, in the presence of Rho kinase
      inhibition, endothelin-1 did not affect endothelium-independent vasodilation (CVC
      at Rho kinase inhibitor vs. endothelin-1+Rho kinase inhibitor sites: 81 +/- 9 vs.
      86 +/- 10%max, P > 0.05). There was no between-site difference in sweating
      throughout (P > 0.05). We show that in young adults, Rho kinase is an important
      mediator of the endothelin-1-mediated attenuation of endothelium-dependent and 
      independent cutaneous vasodilation, and that endothelin-1 does not increase
      sweating.

PMID- 27881400
TI  - Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent
      of changes in body weight in female mice.
AB  - We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1)
      would have increased susceptibility to Western diet-induced "whitening" of brown
      adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT)
      and UCP1 knockout (UCP1-/-) mice, housed at 25 degrees C, were randomized to
      either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and
      1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy
      expenditure, spontaneous physical activity, weight gain, or visceral white AT
      mass. Despite similar susceptibility to weight gain compared with WT, UCP1-/-
      exhibited whitening of brown AT evidenced by a striking ~500% increase in mass
      and appearance of large unilocular adipocytes, increased expression of genes
      related to inflammation, immune cell infiltration, and endoplasmic
      reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit
      protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by
      Western diet (P < 0.05). UCP1-/- mice also developed liver steatosis and glucose
      intolerance, which was worsened by Western diet. Collectively, these findings
      demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown
      AT, glucose intolerance, and induces liver steatosis. Notably, the adverse
      metabolic manifestations of UCP1-/- were independent of changes in body weight,
      visceral adiposity, and energy expenditure. These novel findings uncover a
      previously unrecognized metabolic protective role of UCP1 that is independent of
      its already established role in energy homeostasis.

PMID- 27881401
TI  - Alterations of colonic function in the Winnie mouse model of spontaneous chronic
      colitis.
AB  - : The Winnie mouse, carrying a missense mutation in Muc2, is a model for chronic
      intestinal inflammation demonstrating symptoms closely resembling inflammatory
      bowel disease (IBD). Alterations to the immune environment, morphological
      structure, and innervation of Winnie mouse colon have been identified; however,
      analyses of intestinal transit and colonic functions have not been conducted. In
      this study, we investigated in vivo intestinal transit in radiographic studies
      and in vitro motility of the isolated colon in organ bath experiments. We
      compared neuromuscular transmission using conventional intracellular recording
      between distal colon of Winnie and C57BL/6 mice and smooth muscle contractions
      using force displacement transducers. Chronic inflammation in Winnie mice was
      confirmed by detection of lipocalin-2 in fecal samples over 4 wk and gross
      morphological damage to the colon. Colonic transit was faster in Winnie mice.
      Motility was altered including decreased frequency and increased speed of colonic
      migrating motor complexes and increased occurrence of short and fragmented
      contractions. The mechanisms underlying colon dysfunctions in Winnie mice
      included inhibition of excitatory and fast inhibitory junction potentials,
      diminished smooth muscle responses to cholinergic and nitrergic stimulation, and
      increased number of alpha-smooth muscle actin-immunoreactive cells. We conclude
      that diminished excitatory responses occur both prejunctionally and
      postjunctionally and reduced inhibitory purinergic responses are potentially a
      prejunctional event, while diminished nitrergic inhibitory responses are probably
      due to a postjunction mechanism in the Winnie mouse colon. Many of these changes
      are similar to disturbed motor functions in IBD patients indicating that the
      Winnie mouse is a model highly representative of human IBD. NEW & NOTEWORTHY:
      This is the first study to provide analyses of intestinal transit and whole colon
      motility in an animal model of spontaneous chronic colitis. We found that
      cholinergic and purinergic neuromuscular transmission, as well as the smooth
      muscle cell responses to cholinergic and nitrergic stimulation, is altered in the
      chronically inflamed Winnie mouse colon. The changes to intestinal transit and
      colonic function we identified in the Winnie mouse are similar to those seen in
      inflammatory bowel disease patients.

PMID- 27881404
TI  - Novel insights into fecal incontinence in men.
AB  - : Fecal incontinence (FI) in men is common, yet data on sex differences in
      clinical features, physiology, and treatment are scarce. Our aim was to provide
      insights into FI in males compared with females. Prospectively collected data
      from 73 men and 596 women with FI in a tertiary referral center were analyzed.
      Anorectal physiology, clinical characteristics, and outcome of instrumented
      biofeedback (BF) were recorded. Thirty-one men with FI proceeded to BF and were
      matched with 62 age-matched women with FI who underwent BF. Men with FI had
      higher resting, squeeze, and cough anal sphincter pressures (P < 0.001) and were
      more able to hold a sustained squeeze compared with women (P = 0.04). Men with FI
      had higher rectal pressure and less inadequate rectal pressure on strain and
      higher sensory thresholds (P < 0.05). Men, but not women, with isolated soiling
      had higher anal resting and squeeze pressures compared with those with overt FI
      (P < 0.05). Men were less likely to undergo BF when offered compared with women.
      Baseline symptom severity did not differ between the groups. In men, the absence
      of an organic cause for the FI and the presence of overt FI, but not isolated
      soiling, were correlated with improvement in patient satisfaction following BF.
      The outcomes of 50% reduction in FI episodes, physician assessment, symptoms, and
      quality of life scores after BF all significantly improved in men similarly to
      women. We conclude that men, compared with women, with FI have unique clinical
      features and physiology and are less likely to have investigations and treatment
      despite successful outcome with BF. Future studies to customize treatment in
      males and determine barriers to therapy are warranted. NEW & NOTEWORTHY: Fecal
      incontinence in men is common, yet data on sex differences in clinical features,
      physiology, and treatment are scarce. We provide evidence that men, compared with
      women, with fecal incontinence have unique clinical features and physiology and
      are less likely to have investigations and treatment despite successful outcome
      with anorectal biofeedback therapy.

PMID- 27881402
TI  - Maturity and age influence chief cell ability to transdifferentiate into
      metaplasia.
AB  - : The plasticity of gastric chief cells is exemplified by their ability to
      transdifferentiate into spasmolytic polypeptide-expressing metaplasia (SPEM)
      after parietal cell loss. We sought to determine if chief cell maturity is a
      limiting factor in the capacity to transdifferentiate. Mist1-/- mice, previously
      shown to form only immature chief cells, were treated with DMP-777 or L635 to
      study the capability of these immature chief cells to transdifferentiate into a
      proliferative metaplastic lineage after acute parietal cell loss. Mist1-/- mice
      treated with DMP-777 showed fewer chief cell to SPEM transitions. Mist1-/- mice
      treated with L635 demonstrated significantly fewer proliferative SPEM cells
      compared with control mice. Thus immature chief cells were unable to
      transdifferentiate efficiently into SPEM after acute parietal cell loss. To
      determine whether chief cell age affects transdifferentiation into SPEM, we used
      tamoxifen to induce YFP expression in chief cells of Mist1CreER/+;RosaYFP mice
      and subsequently treated the cells with L635 to induce SPEM at 1 to 3.5 mo after
      tamoxifen treatment. After L635 treatment to induce acute parietal cell loss, 43%
      of all YFP-positive cells at 1 mo posttamoxifen were SPEM cells, of which 44% of
      these YFP-positive SPEM cells were proliferative. By 2 mo after tamoxifen
      induction, only 24% of marked SPEM cells were proliferating. However, by 3.5 mo
      after tamoxifen induction, only 12% of marked chief cells transdifferentiated
      into SPEM and none were proliferative. Thus, as chief cells age, they lose their
      ability to transdifferentiate into SPEM and proliferate. Therefore, both
      functional maturation and age limit chief cell plasticity. NEW & NOTEWORTHY:
      Previous investigations have indicated that spasmolytic polypeptide-expressing
      metaplasia (SPEM) in the stomach arises from transdifferentiation of chief cells.
      Nevertheless, the intrinsic properties of chief cells that influence
      transdifferentiation have been largely unknown. We now report that the ability to
      transdifferentiate into SPEM is impaired in chief cells that lack full functional
      maturation, and as chief cells age, they lose their ability to
      transdifferentiate. Thus chief cell plasticity is dependent on both cell age and
      maturation.

PMID- 27881405
TI  - Effectiveness of individualized lung recruitment strategies at birth: an
      experimental study in preterm lambs.
AB  - Respiratory transition at birth involves rapidly clearing fetal lung liquid and
      preventing efflux back into the lung while aeration is established. We have
      developed a sustained inflation (SIOPT) individualized to volume response and a
      dynamic tidal positive end-expiratory pressure (PEEP) (open lung volume, OLV)
      strategy that both enhance this process. We aimed to compare the effect of each
      with a group managed with PEEP of 8 cmH2O and no recruitment maneuver (No-RM), on
      gas exchange, lung mechanics, spatiotemporal aeration, and lung injury in 127 +/-
      1 day preterm lambs. Forty-eight fetal-instrumented lambs exposed to antenatal
      steroids were ventilated for 60 min after application of the allocated strategy.
      Spatiotemporal aeration and lung mechanics were measured with electrical
      impedance tomography and forced-oscillation, respectively. At study completion,
      molecular and histological markers of lung injury were analyzed. Mean (SD)
      aeration at the end of the SIOPT and OLV groups was 32 (22) and 38 (15) ml/kg,
      compared with 17 (10) ml/kg (180 s) in the No-RM (P = 0.024, 1-way ANOVA). This
      translated into better oxygenation at 60 min (P = 0.047; 2-way ANOVA) resulting
      from better distal lung tissue aeration in SIOPT and OLV. There was no difference
      in lung injury. Neither SIOPT nor OLV achieved homogeneous aeration. Histological
      injury and mRNA biomarker upregulation were more likely in the regions with
      better initial aeration, suggesting volutrauma. Tidal ventilation or an SI
      achieves similar aeration if optimized, suggesting that preventing fluid efflux
      after lung liquid clearance is at least as important as fluid clearance during
      the initial inflation at birth.

PMID- 27881406
TI  - Enrichment of selective miRNAs in exosomes and delivery of exosomal miRNAs in
      vitro and in vivo.
AB  - Exosomes are nanovesicles secreted by cells and contain various molecules
      including protein, lipid, and DNA/RNA. They are crucial mediators of the
      intercellular communication and serve as promising vehicles for drug delivery and
      gene therapy. Recently, accumulating evidence suggests that microRNAs (miRNAs)
      may serve as new and potentially powerful targets for therapeutic interventions
      against various human diseases. However, steadily and effectively delivering
      miRNA mimics or inhibitors to target cells remains a major obstacle. To enhance
      the efficacy of exosome-mediated delivery of miRNA molecules, it is crucial to
      develop a convenient and efficient method to enrich specific miRNAs or antisense
      oligos in isolated exosomes. Here we report a novel method to prepare specific
      miRNA molecule-loaded exosomes. Using a modified calcium chloride-mediated
      transfection method, we successfully enhanced the designated miRNA mimics or
      inhibitors in isolated exosomes directly, instead of transfecting their mother
      cells. We also compared this method with direct transfection of exosomes using
      electroporation. Both methods confirmed that exosomes can serve as cargos to
      deliver a robustly increased amount of selected miRNA mimic(s) or inhibitor(s) to
      the recipient cells. Delivery of these miRNA molecule enriched-exosomes
      subsequently results in highly efficient overexpression or deletion of the
      designated miRNAs in the recipient cells both in vivo and in vitro. Additionally,
      we confirmed that exosome-delivered miRNA mimics or inhibitors are functional in
      the recipient cells. Collectively, we developed a novel protocol to conveniently
      manipulate exosomal miRNAs with high efficiency and successfully deliver the
      exosomal miRNA molecules to recipient cells.

PMID- 27881408
TI  - Fair vaccine pricing please, not random acts of charity.

PMID- 27881407
TI  - Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates
      LPS-induced acute lung injury.
AB  - Sakuranetin is the main isolate flavonoid from Baccharis retusa (Asteraceae)
      leaves and exhibits anti-inflammatory and antioxidative activities. Acute
      respiratory distress syndrome is an acute failure of the respiratory system for
      which effective treatment is urgently necessary. This study investigated the
      preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)
      induced acute lung injury (ALI) in mice. Animals were treated with intranasal
      sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours
      after ALI was induced, lung function, inflammation, macrophages population
      markers, collagen fiber deposition, the extent of oxidative stress, and the
      expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP-9 (TIMP
      1) and NF-kappaB were evaluated. The animals began to show lung alterations 6 h
      after LPS instillation, and these changes persisted until 24 h after LPS
      administration. Preventive and therapeutic treatment with sakuranetin reduced the
      neutrophils in the peripheral blood and in the bronchial alveolar lavage.
      Sakuranetin treatment also reduced macrophage populations, particularly that of
      M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte
      derived chemokines (IL-8 homolog) and NF-kappaB levels, collagen fiber formation,
      MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared
      with LPS animals treated with vehicle. Finally, sakuranetin treatment also
      reduced total protein, and the levels of TNF-alpha and IL-1beta in the lung. This
      study shows that sakuranetin prevented and reduced pulmonary inflammation induced
      by LPS. Because sakuranetin modulates oxidative stress, the NF-kappaB pathway,
      and lung function, it may constitute a novel therapeutic candidate to prevent and
      treat ALI.

PMID- 27881403
TI  - Irritable bowel syndrome: a gut microbiota-related disorder?
AB  - Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI)
      disorders. Despite its prevalence, the pathophysiology of IBS is not well
      understood although multiple peripheral and central factors are implicated.
      Recent studies suggest a role for alterations in gut microbiota in IBS.
      Significant advances in next-generation sequencing technology and bioinformatics
      and the declining cost have now allowed us to better investigate the role of gut
      microbiota in IBS. In the following review, we propose gut microbiota as a
      unifying factor in the pathophysiology of IBS. We first describe how gut
      microbiota can be influenced by factors predisposing individuals to IBS such as
      host genetics, stress, diet, antibiotics, and early life experiences. We then
      highlight the known effects of gut microbiota on mechanisms implicated in the
      pathophysiology of IBS including disrupted gut brain axis (GBA), visceral
      hypersensitivity (VH), altered GI motility, epithelial barrier dysfunction, and
      immune activation. While there are several gaps in the field that preclude us
      from connecting the dots to establish causation, we hope this overview will allow
      us to identify and fill in the voids.

PMID- 27881409
TI  - Intake of individual saturated fatty acids and risk of coronary heart disease in
      US men and women: two prospective longitudinal cohort studies.
AB  - OBJECTIVES:  To investigate the association between long term intake of
      individual saturated fatty acids (SFAs) and the risk of coronary heart disease,
      in two large cohort studies. DESIGN:  Prospective, longitudinal cohort study.
      SETTING:  Health professionals in the United States. PARTICIPANTS:  73 147 women
      in the Nurses' Health Study (1984-2012) and 42 635 men in the Health
      Professionals Follow-up Study (1986-2010), who were free of major chronic
      diseases at baseline. MAIN OUTCOME MEASURE:  Incidence of coronary heart disease
      (n=7035) was self-reported, and related deaths were identified by searching
      National Death Index or through report of next of kin or postal authority. Cases
      were confirmed by medical records review. RESULTS:  Mean intake of SFAs accounted
      for 9.0-11.3% energy intake over time, and was mainly composed of lauric acid
      (12:0), myristic acid (14:0), palmitic acid (16:0), and stearic acid (18:0; 8.8
      10.7% energy). Intake of 12:0, 14:0, 16:0 and 18:0 were highly correlated, with
      Spearman correlation coefficients between 0.38 and 0.93 (all P<0.001). Comparing
      the highest to the lowest groups of individual SFA intakes, hazard ratios of
      coronary heart disease were 1.07 (95% confidence interval 0.99 to 1.15;
      Ptrend=0.05) for 12:0, 1.13 (1.05 to 1.22; Ptrend<0.001) for 14:0, 1.18 (1.09 to
      1.27; Ptrend<0.001) for 16:0, 1.18 (1.09 to 1.28; Ptrend<0.001) for 18:0, and
      1.18 (1.09 to 1.28; Ptrend<0.001) for all four SFAs combined (12:0-18:0), after
      multivariate adjustment of lifestyle factors and total energy intake. Hazard
      ratios of coronary heart disease for isocaloric replacement of 1% energy from
      12:0-18:0 were 0.92 (95% confidence interval 0.89 to 0.96; P<0.001) for
      polyunsaturated fat, 0.95 (0.90 to 1.01; P=0.08) for monounsaturated fat, 0.94
      (0.91 to 0.97; P<0.001) for whole grain carbohydrates, and 0.93 (0.89 to 0.97;
      P=0.001) for plant proteins. For individual SFAs, the lowest risk of coronary
      heart disease was observed when the most abundant SFA, 16:0, was replaced. Hazard
      ratios of coronary heart disease for replacing 1% energy from 16:0 were 0.88 (95%
      confidence interval 0.81 to 0.96; P=0.002) for polyunsaturated fat, 0.92 (0.83 to
      1.02; P=0.10) for monounsaturated fat, 0.90 (0.83 to 0.97; P=0.01) for whole
      grain carbohydrates, and 0.89 (0.82 to 0.97; P=0.01) for plant proteins.
      CONCLUSIONS:  Higher dietary intakes of major SFAs are associated with an
      increased risk of coronary heart disease. Owing to similar associations and high
      correlations among individual SFAs, dietary recommendations for the prevention of
      coronary heart disease should continue to focus on replacing total saturated fat
      with more healthy sources of energy.

PMID- 27881410
TI  - TAZ activation drives fibroblast spheroid growth, expression of profibrotic
      paracrine signals, and context-dependent ECM gene expression.
AB  - Recent studies have implicated the Hippo pathway and its transcriptional
      effectors YAP and TAZ as necessary for fibroblast activation and tissue fibrosis.
      To test the specific and sufficient roles for TAZ in driving autonomous
      fibroblast activation, we cultured NIH3T3 fibroblasts expressing a doxycycline
      inducible nuclear-localized mutant of TAZ (TAZ4SA) in scaffold-free 3D hanging
      drop spheroids, or on matrices of specified mechanical rigidity. Control NIH3T3
      fibroblasts formed spheroids in hanging drop culture that remained stable and
      neither increased nor decreased in size significantly over 15 days. In contrast,
      TAZ4SA-transduced fibroblasts grew robustly in spheroid culture, and expressed
      enhanced levels of genes encoding profibrotic soluble factors connective tissue
      growth factor (CTGF), endothelin-1 (Et-1), and plasminogen activator inhibitor 1
      (PAI-1). However, TAZ4SA expression was unable to enhance expression of
      extracellular matrix (ECM)-encoding genes Col1a1, Col1a2, Col3a1, or Fn1 in
      spheroid culture. Micromechanical testing indicated that spheroids composed of
      either control or TAZ4SA-expressing cells were highly compliant and
      indistinguishable in mechanical properties. In fibroblasts cultured on 2D
      matrices of compliance similar to spheroids, TAZ4SA expression was able to
      enhance contractile force generation, but was unable to enhance ECM gene
      expression. In contrast, culture on stiff hydrogels potentiated TAZ4SA
      enhancement of ECM expression. TAZ4SA enhancement of Col1a1 expression on soft
      matrices was potentiated by TGF-beta1, while on stiff matrices it was abrogated
      by inhibition of myocardin-related transcription factor, demonstrating context
      dependent crosstalk of TAZ with these pathways. These findings demonstrate
      sufficiency of TAZ activation for driving fibroblast proliferation, contraction,
      and soluble profibrotic factor expression, and mechanical context-dependent
      crosstalk of TAZ with other pathways in regulating Col1a1 expression.

PMID- 27881411
TI  - Three distinct cell populations express extracellular matrix proteins and
      increase in number during skeletal muscle fibrosis.
AB  - Tissue extracellular matrix (ECM) provides structural support and creates unique
      environments for resident cells (Bateman JF, Boot-Handford RP, Lamande SR. Nat
      Rev Genet 10: 173-183, 2009; Kjaer M. Physiol Rev 84: 649-98, 2004). However, the
      identities of cells responsible for creating specific ECM components have not
      been determined. In striated muscle, the identity of these cells becomes
      important in disease when ECM changes result in fibrosis and subsequent increased
      tissue stiffness and dysfunction. Here we describe a novel approach to isolate
      and identify cells that maintain the ECM in both healthy and fibrotic muscle.
      Using a collagen I reporter mouse, we show that there are three distinct cell
      populations that express collagen I in both healthy and fibrotic skeletal muscle.
      Interestingly, the number of collagen I-expressing cells in all three cell
      populations increases proportionally in fibrotic muscle, indicating that all cell
      types participate in the fibrosis process. Furthermore, while some profibrotic
      ECM and ECM-associated genes are significantly upregulated in fibrotic muscle,
      the fibrillar collagen gene expression profile is not qualitatively altered. This
      suggests that muscle fibrosis in this model results from an increased number of
      collagen I-expressing cells and not the initiation of a specific fibrotic
      collagen gene expression program. Finally, in fibrotic muscle, we show that these
      collagen I-expressing cell populations differentially express distinct ECM
      proteins-fibroblasts express the fibrillar components of ECM, fibro/adipogenic
      progenitors cells differentially express basal laminar proteins, and skeletal
      muscle progenitor cells differentially express genes important for the satellite
      cell.

PMID- 27881412
TI  - Renin-angiotensin-aldosterone system inhibitors improve membrane stability and
      change gene-expression profiles in dystrophic skeletal muscles.
AB  - Angiotensin-converting enzyme inhibitors (ACEi) and mineralocorticoid receptor
      (MR) antagonists are FDA-approved drugs that inhibit the renin-angiotensin
      aldosterone system (RAAS) and are used to treat heart failure. Combined treatment
      with the ACEi lisinopril and the nonspecific MR antagonist spironolactone
      surprisingly improves skeletal muscle, in addition to heart function and
      pathology in a Duchenne muscular dystrophy (DMD) mouse model. We recently
      demonstrated that MR is present in all limb and respiratory muscles and functions
      as a steroid hormone receptor in differentiated normal human skeletal muscle
      fibers. The goals of the current study were to begin to define cellular and
      molecular mechanisms mediating the skeletal muscle efficacy of RAAS inhibitor
      treatment. We also compared molecular changes resulting from RAAS inhibition with
      those resulting from the current DMD standard-of-care glucocorticoid treatment.
      Direct assessment of muscle membrane integrity demonstrated improvement in
      dystrophic mice treated with lisinopril and spironolactone compared with
      untreated mice. Short-term treatments of dystrophic mice with specific and
      nonspecific MR antagonists combined with lisinopril led to overlapping gene
      expression profiles with beneficial regulation of metabolic processes and
      decreased inflammatory gene expression. Glucocorticoids increased apoptotic,
      proteolytic, and chemokine gene expression that was not changed by RAAS
      inhibitors in dystrophic mice. Microarray data identified potential genes that
      may underlie RAAS inhibitor treatment efficacy and the side effects of
      glucocorticoids. Direct effects of RAAS inhibitors on membrane integrity also
      contribute to improved pathology of dystrophic muscles. Together, these data will
      inform clinical development of MR antagonists for treating skeletal muscles in
      DMD.

PMID- 27881413
TI  - The Drosophila indirect flight muscle myosin heavy chain isoform is insufficient
      to transform the jump muscle into a highly stretch-activated muscle type.
AB  - Stretch activation (SA) is a delayed increase in force that enables high power
      and efficiency from a cyclically contracting muscle. SA exists in various degrees
      in almost all muscle types. In Drosophila, the indirect flight muscle (IFM)
      displays exceptionally high SA force production (FSA), whereas the jump muscle
      produces only minimal FSA We previously found that expressing an embryonic (EMB)
      myosin heavy chain (MHC) isoform in the jump muscle transforms it into a
      moderately SA muscle type and enables positive cyclical power generation. To
      investigate whether variation in MHC isoforms is sufficient to produce even
      higher FSA, we substituted the IFM MHC isoform (IFI) into the jump muscle.
      Surprisingly, we found that IFI only caused a 1.7-fold increase in FSA, less than
      half the increase previously observed with EMB, and only at a high Pi
      concentration, 16 mM. This IFI-induced FSA is much less than what occurs in IFM,
      relative to isometric tension, and did not enable positive cyclical power
      generation by the jump muscle. Both isometric tension and FSA of control fibers
      decreased with increasing Pi concentration. However, for IFI-expressing fibers,
      only isometric tension decreased. The rate of FSA generation was ~1.5-fold faster
      for IFI fibers than control fibers, and both rates were Pi dependent. We conclude
      that MHC isoforms can alter FSA and hence cyclical power generation but that
      isoforms can only endow a muscle type with moderate FSA Highly SA muscle types,
      such as IFM, likely use a different or additional mechanism.

PMID- 27881414
TI  - Enhanced Glucose Consumption and Organic Acid Production by Engineered
      Corynebacterium glutamicum Based on Analysis of a pfkB1 Deletion Mutant.
AB  - In the analysis of a carbohydrate metabolite pathway, we found interesting
      phenotypes in a mutant strain of Corynebacterium glutamicum deficient in pfkB1,
      which encodes fructose-1-phosphate kinase. After being aerobically cultivated
      with fructose as a carbon source, this mutant consumed glucose and produced
      organic acid, predominantly l-lactate, at a level more than 2-fold higher than
      that of the wild-type grown with glucose under conditions of oxygen deprivation.
      This considerably higher fermentation capacity was unique for the combination of
      pfkB1 deletion and cultivation with fructose. In the metabolome and transcriptome
      analyses of this strain, marked intracellular accumulation of fructose-1
      phosphate and significant upregulation of several genes related to the
      phosphoenolpyruvate:carbohydrate phosphotransferase system, glycolysis, and
      organic acid synthesis were identified. We then examined strains overexpressing
      several of the identified genes and demonstrated enhanced glucose consumption and
      organic acid production by these engineered strains, whose values were found to
      be comparable to those of the model pfkB1 deletion mutant grown with fructose. l
      Lactate production by the ppc deletion mutant of the engineered strain was 2,390
      mM (i.e., 215 g/liter) after 48 h under oxygen deprivation, which was a 2.7-fold
      increase over that of the wild-type strain with a deletion of ppc IMPORTANCE:
      Enhancement of glycolytic flux is important for improving microbiological
      production of chemicals, but overexpression of glycolytic enzymes has often
      resulted in little positive effect. That is presumably because the central carbon
      metabolism is under the complex and strict regulation not only transcriptionally
      but also posttranscriptionally, for example, by the ATP/ADP ratio. In contrast,
      we studied a mutant strain of Corynebacterium glutamicum that showed markedly
      enhanced glucose consumption and organic acid production and, based on the
      findings, identified several genes whose overexpression was effective in
      enhancing glycolytic flux under conditions of oxygen deprivation. These results
      will further understanding of the regulatory mechanisms of glycolytic flux and
      can be widely applied to the improvement of the microbial production of useful
      chemicals.

PMID- 27881415
TI  - Whole-Genome Relationships among Francisella Bacteria of Diverse Origins Define
      New Species and Provide Specific Regions for Detection.
AB  - : Francisella tularensis is a highly virulent zoonotic pathogen that causes
      tularemia and, because of weaponization efforts in past world wars, is considered
      a tier 1 biothreat agent. Detection and surveillance of F. tularensis may be
      confounded by the presence of uncharacterized, closely related organisms. Through
      DNA-based diagnostics and environmental surveys, novel clinical and environmental
      Francisella isolates have been obtained in recent years. Here we present 7 new
      Francisella genomes and a comparison of their characteristics to each other and
      to 24 publicly available genomes as well as a comparative analysis of 16S rRNA
      and sdhA genes from over 90 Francisella strains. Delineation of new species in
      bacteria is challenging, especially when isolates having very close genomic
      characteristics exhibit different physiological features-for example, when some
      are virulent pathogens in humans and animals while others are nonpathogenic or
      are opportunistic pathogens. Species resolution within Francisella varies with
      analyses of single genes, multiple gene or protein sets, or whole-genome
      comparisons of nucleic acid and amino acid sequences. Analyses focusing on single
      genes (16S rRNA, sdhA), multiple gene sets (virulence genes, lipopolysaccharide
      [LPS] biosynthesis genes, pathogenicity island), and whole-genome comparisons
      (nucleotide and protein) gave congruent results, but with different levels of
      discrimination confidence. We designate four new species within the genus;
      Francisella opportunistica sp. nov. (MA06-7296), Francisella salina sp. nov.
      (TX07-7308), Francisella uliginis sp. nov. (TX07-7310), and Francisella
      frigiditurris sp. nov. (CA97-1460). This study provides a robust comparative
      framework to discern species and virulence features of newly detected Francisella
      bacteria. IMPORTANCE: DNA-based detection and sequencing methods have identified
      thousands of new bacteria in the human body and the environment. In most cases,
      there are no cultured isolates that correspond to these sequences. While DNA
      based approaches are highly sensitive, accurately assigning species is difficult
      without known near relatives for comparison. This ambiguity poses challenges for
      clinical cases, disease epidemics, and environmental surveillance, for which
      response times must be short. Many new Francisella isolates have been identified
      globally. However, their species designations and potential for causing human
      disease remain ambiguous. Through detailed genome comparisons, we identified
      features that differentiate F. tularensis from clinical and environmental
      Francisella isolates and provide a knowledge base for future comparison of
      Francisella organisms identified in clinical samples or environmental surveys.

PMID- 27881416
TI  - Metagenomics of Two Severe Foodborne Outbreaks Provides Diagnostic Signatures and
      Signs of Coinfection Not Attainable by Traditional Methods.
AB  - : Diagnostic testing for foodborne pathogens relies on culture-based techniques
      that are not rapid enough for real-time disease surveillance and do not give a
      quantitative picture of pathogen abundance or the response of the natural
      microbiome. Powerful sequence-based culture-independent approaches, such as
      shotgun metagenomics, could sidestep these limitations and potentially reveal a
      pathogen-specific signature on the microbiome that would have implications not
      only for diagnostics but also for better understanding disease progression and
      pathogen ecology. However, metagenomics have not yet been validated for foodborne
      pathogen detection. Toward closing these gaps, we applied shotgun metagenomics to
      stool samples collected from two geographically isolated (Alabama and Colorado)
      foodborne outbreaks, where the etiologic agents were identified by culture
      dependent methods as distinct strains of Salmonella enterica subsp. enterica
      serovar Heidelberg. Metagenomic investigations were consistent with the culture
      based findings and revealed, in addition, the in situ abundance and level of
      intrapopulation diversity of the pathogen, the possibility of coinfections with
      Staphylococcus aureus, overgrowth of commensal Escherichia coli, and significant
      shifts in the gut microbiome during infection relative to reference healthy
      samples. Additionally, we designed our bioinformatics pipeline to deal with
      several challenges associated with the analysis of clinical samples, such as the
      high frequency of coeluting human DNA sequences and assessment of the virulence
      potential of pathogens. Comparisons of these results to those of other studies
      revealed that in several, but not all, cases of diarrheal outbreaks, the disease
      and healthy states of the gut microbial community might be distinguishable,
      opening new possibilities for diagnostics. IMPORTANCE: Diagnostic testing for
      enteric pathogens has relied for decades on culture-based techniques, but a total
      of 38.4 million cases of foodborne illness per year cannot be attributed to
      specific causes. This study describes new culture-independent metagenomic
      approaches and the associated bioinformatics pipeline to detect and type the
      causative agents of microbial disease with unprecedented accuracy, opening new
      possibilities for the future development of health technologies and diagnostics.
      Our tools and approaches should be applicable to other microbial diseases in
      addition to foodborne diarrhea.

PMID- 27881417
TI  - Analysis of Germination Capacity and Germinant Receptor (Sub)clusters of Genome
      Sequenced Bacillus cereus Environmental Isolates and Model Strains.
AB  - : Spore germination of 17 Bacillus cereus food isolates and reference strains was
      evaluated using flow cytometry analysis in combination with fluorescent staining
      at a single-spore level. This approach allowed for rapid collection of
      germination data under more than 20 conditions, including heat activation of
      spores, germination in complex media (brain heart infusion [BHI] and tryptone soy
      broth [TSB]), and exposure to saturating concentrations of single amino acids and
      the combination of alanine and inosine. Whole-genome sequence comparison revealed
      a total of 11 clusters of operons encoding germinant receptors (GRs): GerK, GerI,
      and GerL were present in all strains, whereas GerR, GerS, GerG, GerQ, GerX, GerF,
      GerW, and GerZ (sub)clusters showed a more diverse presence/absence in different
      strains. The spores of tested strains displayed high diversity with regard to
      their sensitivity and responsiveness to selected germinants and heat activation.
      The two laboratory strains, B. cereus ATCC 14579 and ATCC 10987, and 11 food
      isolates showed a good germination response under a range of conditions, whereas
      four other strains (B. cereus B4085, B4086, B4116, and B4153) belonging to
      phylogenetic group IIIA showed a very weak germination response even in BHI and
      TSB media. Germination responses could not be linked to specific (combinations
      of) GRs, but it was noted that the four group IIIA strains contained pseudogenes
      or variants of subunit C in their gerL cluster. Additionally, two of those
      strains (B4086 and B4153) carried pseudogenes in the gerK and gerRI (sub)clusters
      that possibly affected the functionality of these GRs. IMPORTANCE: Germination of
      bacterial spores is a critical step before vegetative growth can resume. Food
      products may contain nutrient germinants that trigger germination and outgrowth
      of Bacillus species spores, possibly leading to food spoilage or foodborne
      illness. Prediction of spore germination behavior is, however, very challenging,
      especially for spores of natural isolates that tend to show more diverse
      germination responses than laboratory strains. The approach used has provided
      information on the genetic diversity in GRs and corresponding subclusters encoded
      by B. cereus strains, as well as their germination behavior and possible
      associations with GRs, and it provides a basis for further extension of knowledge
      on the role of GRs in B. cereus (group member) ecology and transmission to the
      host.

PMID- 27881418
TI  - Environmental Pseudomonads Inhibit Cystic Fibrosis Patient-Derived Pseudomonas
      aeruginosa.
AB  - : Pseudomonas aeruginosa is an opportunistic pathogen which is evolving
      resistance to many currently used antibiotics. While much research has been
      devoted to the roles of pathogenic P. aeruginosa in cystic fibrosis (CF)
      patients, less is known of its ecological properties. P. aeruginosa dominates the
      lungs during chronic infection in CF patients, yet its abundance in some
      environments is less than that of other diverse groups of pseudomonads. Here, we
      sought to determine if clinical isolates of P. aeruginosa are vulnerable to
      environmental pseudomonads that dominate soil and water habitats in one-to-one
      competitions which may provide a source of inhibitory factors. We isolated a
      total of 330 pseudomonads from diverse habitats of soil and freshwater ecosystems
      and competed these strains against one another to determine their capacity for
      antagonistic activity. Over 900 individual inhibitory events were observed.
      Extending the analysis to P. aeruginosa isolates revealed that clinical isolates,
      including ones with increased alginate production, were susceptible to
      competition by multiple environmental strains. We performed transposon
      mutagenesis on one isolate and identified an ~14.8-kb locus involved in
      antagonistic activity. Only two other environmental isolates were observed to
      carry the locus, suggesting the presence of additional unique compounds or
      interactions among other isolates involved in outcompeting P. aeruginosa This
      collection of strains represents a source of compounds that are active against
      multiple pathogenic strains. With the evolution of resistance of P. aeruginosa to
      currently used antibiotics, these environmental strains provide opportunities for
      novel compound discovery against drug-resistant clinical strains. IMPORTANCE: We
      demonstrate that clinical CF-derived isolates of P. aeruginosa are susceptible to
      competition in the presence of environmental pseudomonads. We observed that many
      diverse environmental strains exhibited varied antagonistic profiles against a
      panel of clinical P. aeruginosa isolates, suggesting the presence of distinct
      mechanisms of inhibition among these ecological strains. Understanding the
      properties of these antagonistic events offers the potential for discoveries of
      antimicrobial compounds or metabolic pathways important to the development of
      novel treatments for P. aeruginosa infections.

PMID- 27881419
TI  - Oral Administration of a Select Mixture of Bacillus Probiotics Affects the Gut
      Microbiota and Goblet Cell Function following Escherichia coli Challenge in Newly
      Weaned Pigs of Genotype MUC4 That Are Supposed To Be Enterotoxigenic E. coli
      F4ab/ac Receptor Negative.
AB  - : Structural disruption of the gut microbiota and impaired goblet cell function
      are collateral etiologic factors in enteric diseases. Low, moderate, or high
      doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally
      administered to piglets of genotype MUC4 that are supposed to be F4-expressing
      enterotoxigenic Escherichia coli strain (F4+ ETEC) F4ab/ac receptor negative
      (i.e., MUC4-resistant piglets) for 1 week before F4+ ETEC challenge. The luminal
      contents were collected from the mucosa of the colon on day 8 after F4+ ETEC
      challenge. The BLS mix attenuated E. coli-induced expansion of Bacteroides
      uniformis, Eubacterium eligens, Acetanaerobacterium, and Sporobacter populations.
      Clostridium and Turicibacter populations increased following F4+ ETEC challenge
      in pigs pretreated with low-dose BLS mix. Lactobacillus gasseri and Lactobacillus
      salivarius populations increased after administration of BLS mix during E. coli
      infection. The beneficial effects of BLS mix were due in part to the expansion of
      certain Clostridium, Lactobacillus, and Turicibacter populations, with a
      corresponding increase in the number of goblet cells in the ileum via upregulated
      Atoh1 expression, in turn increasing MUC2 production and thus preserving the
      mucus barrier and enhancing host defenses against enteropathogenic bacteria.
      However, excessive BLS mix consumption may increase the risk for enteritis,
      partly through disruption of colonic microbial ecology, characterized by
      expansion of Proteobacteria and impaired goblet cell function in the ileum. Our
      findings suggest that oral administration of BLS mix reprograms the gut
      microbiota and enhances goblet cell function to ameliorate enteritis. IMPORTANCE:
      The present study is important for improving our understanding of the protective
      role of probiotics against Escherichia coli infection in piglets. Structural
      disruption of the gut microbiota and impaired goblet cell function are collateral
      etiologic factors in enteric diseases. In this study, low, moderate, or high
      doses of a Bacillus licheniformis-B. subtilis mixture (BLS mix) were orally
      administered to MUC4-resistant piglets for 1 week before the F4-expressing ETEC
      strain (F4+ ETEC) challenge. Our findings suggest that oral administration of BLS
      mix reprograms the gut microbiota and enhances goblet cell function to ameliorate
      enteritis.

PMID- 27881421
TI  - Common Variant in Glycoprotein Ia Increases Long-Term Adverse Events Risk After
      Coronary Artery Bypass Graft Surgery.
AB  - BACKGROUND: This study was aimed to investigate the clinical relevance between
      glycoprotein Ia (GPIA) rs1126643C/T polymorphism and the outcome of coronary
      artery disease after coronary artery bypass graft (CABG) surgery and explore the
      involved potential mechanisms. METHODS AND RESULTS: We genotyped GPIA rs1126643
      polymorphism of 1592 patients who underwent CABG and followed up for a median
      period of 72.8 months. Patients who are GPIA rs1126643 T-allele carriers have a
      higher major adverse cardiac or cerebrovascular events risk post-CABG than those
      who are CC homozygotes (hazard ratio [HR]=1.29; P=0.022). The clinical
      association between the risk allele (T) carriage and major adverse cardiac or
      cerebrovascular events was confirmed in another cohort study, which included 646
      CABG patients from various health centers across China. Meanwhile, rs1126643 T
      allele was also linked with increased risk of major adverse cardiac or
      cerebrovascular events (HR=1.73; P=0.019). To explore the underlying mechanisms,
      we prospectively recruited 131 coronary artery disease patients, assessed their
      platelet aggregation function, and focused on detecting their GPIA mRNA level and
      protein expression. Results showed that patients with rs1126643 T allele have
      elevated platelet aggregation activity (P=0.029) when protein expression is
      increased (P<0.001) and not affected by glycoprotein Ia mRNA level. CONCLUSIONS:
      The synonymous common variant, GPIA rs1126643, increases the long-term adverse
      events risk of CABG by augmenting GPIa protein expression and enhancing platelet
      aggregation function. This finding can serve as the implication of improving
      secondary prevention of CABG patients.

PMID- 27881422
TI  - Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic
      Syndrome: Relevance to Atherosclerosis.
AB  - BACKGROUND: The contribution of high-density lipoprotein to cardiovascular
      benefit is closely linked to its role in the cellular cholesterol efflux process;
      however, various clinical and biochemical variables are known to modulate the
      overall cholesterol efflux process. The aim of this study was to evaluate the
      extent to which clinical and biological anomalies associated with the
      establishment of the metabolic syndrome modulate cholesterol efflux capacity and
      contribute to development of atherosclerosis. METHODS AND RESULTS: This study
      involved patients (n=1202) displaying atherogenic dyslipidemia in primary
      prevention who were referred to our prevention center. Among these patients, 25%
      presented at least 3 criteria of the metabolic syndrome, as defined by the
      National Cholesterol Education Program Adult Treatment Panel III. We measured the
      capacity of 40-fold diluted serum to mediate cholesterol efflux from cholesterol
      loaded human THP-1 macrophages. Cholesterol efflux capacity was reduced
      progressively by 4% to 11% (P<0.0001) as a function of the increasing number of
      coexisting criteria for the metabolic syndrome from 1 to 5. This observation was
      primarily related to reductions in scavenger receptor class B member 1 and ATP
      binding cassette subfamily G member 1-dependent efflux. Multivariate analyses
      indicate that serum efflux capacity was significantly associated with established
      metabolic syndrome (odds ratio 0.45; 95% CI 0.28-0.72; P=0.009) independent of
      age, low-density lipoprotein cholesterol, status with regard to lipid-lowering
      therapy, smoking status, and alcohol consumption. CONCLUSIONS: Our study revealed
      that individual criteria of metabolic syndrome are closely related
      synergistically to cholesterol efflux capacity. In addition, established
      metabolic syndrome and cholesterol efflux capacity were independently associated
      with clinical features of atherosclerosis.

PMID- 27881420
TI  - Elongation of Long-Chain Fatty Acid Family Member 6 (Elovl6)-Driven Fatty Acid
      Metabolism Regulates Vascular Smooth Muscle Cell Phenotype Through AMP-Activated
      Protein Kinase/Kruppel-Like Factor 4 (AMPK/KLF4) Signaling.
AB  - BACKGROUND: Fatty acids constitute the critical components of cell structure and
      function, and dysregulation of fatty acid composition may exert diverging
      vascular effects including proliferation, migration, and differentiation of
      vascular smooth muscle cells (VSMCs). However, direct evidence for this
      hypothesis has been lacking. We investigated the role of elongation of long-chain
      fatty acid member 6 (Elovl6), a rate-limiting enzyme catalyzing the elongation of
      saturated and monounsaturated long-chain fatty acid, in the regulation of
      phenotypic switching of VSMC. METHODS AND RESULTS: Neointima formation following
      wire injury was markedly inhibited in Elovl6-null (Elovl6-/-) mice, and cultured
      VSMCs with siRNA-mediated knockdown of Elovl6 was barely responsive to PDGF-BB.
      Elovl6 inhibition induced cell cycle suppressors p53 and p21 and reduced the
      mammalian targets of rapamycin (mTOR) phosphorylation and VSMC marker expression.
      These changes are ascribed to increased palmitate levels and reduced oleate
      levels, changes that lead to reactive oxygen species (ROS) production and
      resulting AMP-activated protein kinase (AMPK) activation. Notably, Elovl6
      inhibition robustly induced the pluripotency gene Kruppel-like factor 4 (KLF4)
      expression in VSMC, and KLF4 knockdown significantly attenuated AMPK-induced
      phenotypic switching of VSMC, indicating that KLF4 is a bona fide target of AMPK.
      CONCLUSIONS: We demonstrate for the first time that dysregulation of Elovl6
      driven long-chain fatty acid metabolism induces phenotypic switching of VSMC via
      ROS production and AMPK/KLF4 signaling that leads to growth arrest and
      downregulation of VSMC marker expression. The modulation of Elovl6-mediated
      cellular processes may provide an intriguing approach for tackling
      atherosclerosis and postangioplasty restenosis.

PMID- 27881423
TI  - Association of Systemic Arterial Properties With Right Ventricular Morphology:
      The Multi-Ethnic Study of Atherosclerosis (MESA)-Right Ventricle Study.
AB  - BACKGROUND: Systemic arterial stiffness is recognized as a major contributor to
      development of left ventricular dysfunction and failure; however, the
      relationship of systemic arterial properties and the right ventricle (RV) is
      unknown. METHODS AND RESULTS: The associations between systemic arterial measures
      (total arterial compliance [TAC], systemic vascular resistance [SVR], and aortic
      augmentation index [AI]) and RV morphology (mass, end-systolic [RVESV] and end
      diastolic volume [RVEDV], and ejection fraction [RVEF]) were examined using data
      from the Multi-Ethnic Study of Atherosclerosis. All analyses were adjusted for
      anthropometric, demographic, and clinical variables and the corresponding left
      ventricular parameter. A total of 3842 subjects without clinical cardiovascular
      disease were included with a mean age of 61 years, 48% male, 39% non-Hispanic
      white, 25% Chinese-American, 23% Hispanic, and 13% black. RV measures were within
      normal range for age and sex. A 1-mL/mm Hg decrease in TAC was associated with
      3.9-mL smaller RVESV, 7.6-mL smaller RVEDV, and 2.4-g lower RV mass. A 5-Wood
      unit increase in SVR was associated with 0.6-mL decrease in RVESV, 1.7-mL
      decrease in RVEDV, and 0.4-g decrease in RV mass. A 1% increase in AI was
      associated with 0.2-mL decrease in RVEDV. We found significant effect
      modification by age, sex, and race for some of these relationships, with males,
      whites, and younger individuals having greater decreases in RV volumes and mass.
      CONCLUSIONS: Markers of increased systemic arterial load were associated with
      smaller RV volumes and lower RV mass in a population of adults without clinical
      cardiovascular disease.

PMID- 27881424
TI  - Temporal Reduction in Chronotropic Index Predicts Risk of Cardiovascular Death
      Among Healthy Middle-Aged Men: a 28-Year Follow-Up Study.
AB  - BACKGROUND: Chronotropic index is a standardized measure of heart rate (HR)
      increment during exercise that reflects the combined effects of age, resting HR,
      and physical fitness. Low chronotropic index has been reported to predict disease
      and death. We tested whether temporal change in chronotropic index over 7 years
      influenced risk of cardiovascular death through up to 28 years. METHODS AND
      RESULTS: Chronotropic index was calculated ([achieved maximal HR-resting HR]/[age
      predicted maximal HR-resting HR]) after a symptom-limited bicycle ECG exercise
      test in 1420 healthy men at 2 examinations 7 years apart, in 1972 and 1979.
      Events of cardiovascular death were registered by manual scrutiny of all
      participants' hospital charts and the Norwegian Cause of Death Registry. The
      participants were divided into quartiles of temporal change in chronotropic
      index, with quartile one having the most negative value. Cox proportional hazard
      regression models were used to estimate risks and adjusted for classical
      cardiovascular risk factors. Incidence of cardiovascular death was 310 (22%)
      during median of 21 years of follow-up. After multivariable adjustment, and
      comparison with quartile four (mean +0.11), quartiles one (-0.16), two (-0.04),
      and three (+0.02) were associated with hazard ratios 1.50 (95% CI 1.10-2.05),
      1.10 (0.79-1.53), and 1.04 (0.74-1.45) for cardiovascular death. Results remained
      robust also after exclusion of 31 participants with exercise ECG-induced signs of
      coronary ischemia. CONCLUSIONS: Temporal reduction in chronotropic index was
      associated with increased long-term risk of cardiovascular death and might be a
      clinically important predictor when assessing risk in healthy individuals over a
      longer time.

PMID- 27881425
TI  - Relationship Between Language Preference and Intravenous Thrombolysis Among Acute
      Ischemic Stroke Patients.
AB  - BACKGROUND: Approximately 20% of the US population primarily speaks a language
      other than English at home. Yet the effect of language preference on treatment of
      acute ischemic stroke (AIS) patients remains unknown. We aimed to evaluate the
      influence of language preference on AIS patients' receipt of intravenous (IV)
      thrombolysis. METHODS AND RESULTS: We analyzed data from 3894 AIS patients who
      participated in the American Heart Association "Get With The Guidelines(r)
      Stroke" program at our hospital from January 1, 2003 to April 30, 2014.
      Information included patients' language in which they preferred to receive
      medical care. We used descriptive statistics and stepwise logistic regression
      models to examine associations between patients' language preference and receipt
      of IV thrombolysis, adjusting for relevant covariates. A total of 306/3295 (9.3%)
      AIS patients preferred to speak a non-English language and represented 25
      different languages. Multivariable analyses adjusting for other socioeconomic
      factors showed that non-English-preferring patients were more likely than English
      preferring patients to receive IV thrombolysis (OR=1.64; CI=1.09-2.48; P=0.02).
      However, in models that also included age, sex, and initial NIH Stroke Scale,
      patients' language preference was no longer significant (OR 1.38; CI=0.88-2.15;
      P=0.16), but NIH Stroke Scale was strongly associated with receiving IV
      thrombolysis (OR=1.15 per point; CI=1.13-1.16; P<0.0001). CONCLUSIONS: Contrary
      to our hypothesis, non-English-preferring was not associated with lower rates of
      IV thrombolysis among AIS patients once initial stroke severity was accounted
      for.

PMID- 27881426
TI  - Contemporary Trends and Age-Specific Sex Differences in Management and Outcome
      for Patients With ST-Segment Elevation Myocardial Infarction.
AB  - BACKGROUND: Age- and sex-specific differences exist in the treatment and outcome
      of ST-elevation myocardial infarction (STEMI). We sought to describe age- and sex
      matched contemporary trends of in-hospital management and outcome of patients
      with STEMI. METHODS AND RESULTS: We analyzed data from 5 Italian nationwide
      prospective registries, conducted between 2001 and 2014, including consecutive
      patients with STEMI. All the analyses were age- and sex-matched, considering 4
      age classes: <55, 55 to 64, 65 to 74, and >=75 years. A total of 13 235 patients
      were classified as having STEMI (72.1% men and 27.9% women). A progressive shift
      from thrombolysis to primary percutaneous coronary intervention occurred over
      time, with a concomitant increase in overall reperfusion rates (P for trend
      <0.0001), which was consistent across sex and age classes. The crude rates of in
      hospital death were 3.2% in men and 8.4% in women (P<0.0001), with a significant
      increase over age classes for both sexes and a significant decrease over time for
      both sexes (all P for trend <0.01). On multivariable analysis, age (odds ratio
      1.09, 95% CI 1.07-1.10, P<0.0001) and female sex (odds ratio 1.44, 95% CI 1.07
      1.93, P=0.009) were found to be significantly associated with in-hospital
      mortality after adjustment for other risk factors, but no significant interaction
      between these 2 variables was observed (P for interaction=0.61). CONCLUSIONS:
      Despite a nationwide shift from thrombolytic therapy to primary percutaneous
      coronary intervention for STEMI affecting both sexes and all ages, women continue
      to experience higher in-hospital mortality than men, irrespective of age.

PMID- 27881427
TI  - Ischemic Stroke Rate Increases in Young Adults: Evidence for a Generational
      Effect?
AB  - BACKGROUND: The incidence rates of ischemic stroke and ST-segment elevation
      myocardial infarction (STEMI) have decreased significantly in the United States
      since 1950. However, there is evidence of flattening of this trend or increasing
      rates for stroke in patients younger than 50 years. The objective of this study
      was to examine the changes in incidence rates of stroke and STEMI using an age
      period-cohort model with statewide data from New Jersey. METHODS AND RESULTS: We
      obtained stroke and STEMI data for the years 1995-2014 from the Myocardial
      Infarction Data Acquisition System, a database of hospital discharges in New
      Jersey. Rates by age for the time periods 1994-1999, 2000-2004, 2005-2009, and
      2010-2014 were obtained using census estimates as denominators for each age group
      and period. The rate of stroke more than doubled in patients aged 35 to 39 years
      from 1995-1999 to 2010-2014 (rate ratio [RR], 2.47; 95% CI, 2.07-2.96
      [P<0.0001]). We also found increased rates of stroke in those aged 40 to 44, 45
      to 49, and 50 to 54 years. Strokes rates in those older than 55 years decreased
      during these time periods. Those born from 1945-1954 had lower age-adjusted rates
      of stroke than those born both in the prior 20 years and in the following 20
      years. STEMI rates, in contrast, decreased in all age groups and in each
      successive birth cohort. CONCLUSIONS: There appears to be a significant birth
      cohort effect in the risk of stroke, where patients born from 1945-1954 have
      lower age-adjusted rates of stroke compared with those born in earlier and later
      years.

PMID- 27881429
TI  - A review of validation strategies for computational drug repositioning.
AB  - Repositioning of previously approved drugs is a promising methodology because it
      reduces the cost and duration of the drug development pipeline and reduces the
      likelihood of unforeseen adverse events. Computational repositioning is
      especially appealing because of the ability to rapidly screen candidates in
      silico and to reduce the number of possible repositioning candidates. What is
      unclear, however, is how useful such methods are in producing clinically
      efficacious repositioning hypotheses. Furthermore, there is no agreement in the
      field over the proper way to perform validation of in silico predictions, and in
      fact no systematic review of repositioning validation methodologies. To address
      this unmet need, we review the computational repositioning literature and capture
      studies in which authors claimed to have validated their work. Our analysis
      reveals widespread variation in the types of strategies, predictions made and
      databases used as 'gold standards'. We highlight a key weakness of the most
      commonly used strategy and propose a path forward for the consistent analytic
      validation of repositioning techniques.

PMID- 27881430
TI  - A comprehensive review and comparison of different computational methods for
      protein remote homology detection.
AB  - Protein remote homology detection is one of the most fundamental and central
      problems for the studies of protein structures and functions, aiming to detect
      the distantly evolutionary relationships among proteins via computational
      methods. During the past decades, many computational approaches have been
      proposed to solve this important task. These methods have made a substantial
      contribution to protein remote homology detection. Therefore, it is necessary to
      give a comprehensive review and comparison on these computational methods. In
      this article, we divide these computational approaches into three categories,
      including alignment methods, discriminative methods and ranking methods. Their
      advantages and disadvantages are discussed in a comprehensive perspective, and
      their performance is compared on widely used benchmark data sets. Finally, some
      open questions in this field are further explored and discussed.

PMID- 27881432
TI  - What (not) to expect when classifying rare events.
AB  - When building classifiers, it is natural to require that the classifier correctly
      estimates the event probability (Constraint 1), that it has equal sensitivity and
      specificity (Constraint 2) or that it has equal positive and negative predictive
      values (Constraint 3). We prove that in the balanced case, where there is equal
      proportion of events and non-events, any classifier that satisfies one of these
      constraints will always satisfy all. Such unbiasedness of events and non-events
      is much more difficult to achieve in the case of rare events, i.e. the situation
      in which the proportion of events is (much) smaller than 0.5. Here, we prove that
      it is impossible to meet all three constraints unless the classifier achieves
      perfect predictions. Any non-perfect classifier can only satisfy at most one
      constraint, and satisfying one constraint implies violating the other two
      constraints in a specific direction. Our results have implications for
      classifiers optimized using g-means or F1-measure, which tend to satisfy
      Constraints 2 and 1, respectively. Our results are derived from basic probability
      theory and illustrated with simulations based on some frequently used
      classifiers.

PMID- 27881428
TI  - Genome, transcriptome and proteome: the rise of omics data and their integration
      in biomedical sciences.
AB  - Advances in the technologies and informatics used to generate and process large
      biological data sets (omics data) are promoting a critical shift in the study of
      biomedical sciences. While genomics, transcriptomics and proteinomics, coupled
      with bioinformatics and biostatistics, are gaining momentum, they are still, for
      the most part, assessed individually with distinct approaches generating
      monothematic rather than integrated knowledge. As other areas of biomedical
      sciences, including metabolomics, epigenomics and pharmacogenomics, are moving
      towards the omics scale, we are witnessing the rise of inter-disciplinary data
      integration strategies to support a better understanding of biological systems
      and eventually the development of successful precision medicine. This review cuts
      across the boundaries between genomics, transcriptomics and proteomics,
      summarizing how omics data are generated, analysed and shared, and provides an
      overview of the current strengths and weaknesses of this global approach. This
      work intends to target students and researchers seeking knowledge outside of
      their field of expertise and fosters a leap from the reductionist to the global
      integrative analytical approach in research.

PMID- 27881431
TI  - Predictive approaches for drug combination discovery in cancer.
AB  - Drug combinations have been proposed as a promising therapeutic strategy to
      overcome drug resistance and improve efficacy of monotherapy regimens in cancer.
      This strategy aims at targeting multiple components of this complex disease.
      Despite the increasing number of drug combinations in use, many of them were
      empirically found in the clinic, and the molecular mechanisms underlying these
      drug combinations are often unclear. These challenges call for rational,
      systematic approaches for drug combination discovery. Although high-throughput
      screening of single-agent therapeutics has been successfully implemented, it is
      not feasible to test all possible drug combinations, even for a reduced subset of
      anticancer drugs. Hence, in vitro and in vivo screening of a large number of drug
      combinations are not practical. Therefore, devising computational methods to
      efficiently explore the space of drug combinations and to discover efficacious
      combinations has attracted a lot of attention from the scientific community in
      the past few years. Nevertheless, in the absence of consensus regarding the
      computational approaches used to predict efficacious drug combinations, a
      plethora of methods, techniques and hypotheses have been developed to date, while
      the research field lacks an elaborate categorization of the existing
      computational methods and the available data sources. In this manuscript, we
      review and categorize the state-of-the-art computational approaches for drug
      combination prediction, and elaborate on the limitations of these methods and the
      existing challenges. We also discuss about the recent pan-cancer drug combination
      data sets and their importance in revising the available methods or developing
      more performant approaches.

PMID- 27881433
TI  - Multifaceted DMRT1 Reveals Additional Roles in Spermatogenesis.

PMID- 27881434
TI  - Zika related microcephaly may appear after birth, study finds.

PMID- 27881435
TI  - Healthcare comes to standstill in east Aleppo as last hospitals are destroyed.

PMID- 27881436
TI  - Knockdown of histidine-rich calcium-binding protein (HRC) suppresses liver
      fibrosis by inhibiting the activation of hepatic stellate cells.
AB  - The histidine-rich calcium-binding protein (HRC) is a regulator of Ca2+
      homeostasis and it plays a significant role in hepatocellular carcinoma (HCC)
      progression. However, the relationship between HRC and liver fibrogenesis is
      still unknown. Our data demonstrates that HRC was upregulated in fibrotic liver
      and activated hepatic stellate cells (HSCs). TGF-beta treatment increased alpha
      SMA and HRC expression dose-dependently in HSCs. Repression of HRC reduced alpha
      SMA, CTGF and collagen expression, and inhibited HSC proliferation and migration.
      In addition, we found that the anti-fibrosis effect of HRC knockdown was
      associated with endoplasmic reticulum (ER) stress. Silencing of HRC decreased the
      expression of ER stress and autophagy markers. Moreover, ER stress agonist
      thapsigargin (TG) enhanced, whereas ER stress antagonist 4-phenylbutyric acid (4
      PBA) alleviated HSCs activation and autophagy. In conclusion, these data indicate
      that depletion of HRC inhibited HSC activation through the ER stress pathway, and
      HRC may be a potential regulator of liver fibrosis.

PMID- 27881437
TI  - Casein kinase II is required for proper cell division and acts as a negative
      regulator of centrosome duplication in Caenorhabditis elegans embryos.
AB  - Centrosomes are the primary microtubule-organizing centers that orchestrate
      microtubule dynamics during the cell cycle. The correct number of centrosomes is
      pivotal for establishing bipolar mitotic spindles that ensure accurate
      segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle,
      one daughter per mother centriole, the process of which requires highly
      coordinated actions among core factors and modulators. Protein phosphorylation is
      shown to regulate the stability, localization and activity of centrosome
      proteins. Here, we report the function of Casein kinase II (CK2) in early
      Caenorhabditis elegans embryos. The catalytic subunit (KIN-3/CK2alpha) of CK2
      localizes to nuclei, centrosomes and midbodies. Inactivating CK2 leads to cell
      division defects, including chromosome missegregation, cytokinesis failure and
      aberrant centrosome behavior. Furthermore, depletion or inhibiting kinase
      activity of CK2 results in elevated ZYG-1 levels at centrosomes, restoring
      centrosome duplication and embryonic viability to zyg-1 mutants. Our data suggest
      that CK2 functions in cell division and negatively regulates centrosome
      duplication in a kinase-dependent manner.

PMID- 27881438
TI  - Ole1, fatty acid desaturase, is required for Atg9 delivery and isolation membrane
      expansion during autophagy in Saccharomyces cerevisiae.
AB  - Macroautophagy, a major degradation pathway of cytoplasmic components, is carried
      out through formation of a double-membrane structure, the autophagosome. Although
      the involvement of specific lipid species in the formation process remains
      largely obscure, we recently showed that mono-unsaturated fatty acids (MUFA)
      generated by stearoyl-CoA desaturase 1 (SCD1) are required for autophagosome
      formation in mammalian cells. To obtain further insight into the role of MUFA in
      autophagy, in this study we analyzed the autophagic phenotypes of the yeast
      mutant of OLE1, an orthologue of SCD1. Deltaole1 cells were defective in nitrogen
      starvation-induced autophagy, and the Cvt pathway, when oleic acid was not
      supplied. Defects in elongation of the isolation membrane led to a defect in
      autophagosome formation. In the absence of Ole1, the transmembrane protein Atg9
      was not able to reach the pre-autophagosomal structure (PAS), the site of
      autophagosome formation. Thus, autophagosome formation requires Ole1 during the
      delivery of Atg9 to the PAS/autophagosome from its cellular reservoir.

PMID- 27881439
TI  - Optimisation of high-quality total ribonucleic acid isolation from cartilaginous
      tissues for real-time polymerase chain reaction analysis.
AB  - OBJECTIVES: Studies which consider the molecular mechanisms of degeneration and
      regeneration of cartilaginous tissues are seriously hampered by problematic
      ribonucleic acid (RNA) isolations due to low cell density and the dense,
      proteoglycan-rich extracellular matrix of cartilage. Proteoglycans tend to co
      purify with RNA, they can absorb the full spectrum of UV light and they are
      potent inhibitors of polymerase chain reaction (PCR). Therefore, the objective of
      the present study is to compare and optimise different homogenisation methods and
      RNA isolation kits for an array of cartilaginous tissues. MATERIALS AND METHODS:
      Tissue samples such as the nucleus pulposus (NP), annulus fibrosus (AF),
      articular cartilage (AC) and meniscus, were collected from goats and homogenised
      by either the MagNA Lyser or Freezer Mill. RNA of duplicate samples was
      subsequently isolated by either TRIzol (benchmark), or the RNeasy Lipid Tissue,
      RNeasy Fibrous Tissue, or Aurum Total RNA Fatty and Fibrous Tissue kits. RNA
      yield, purity, and integrity were determined and gene expression levels of type
      II collagen and aggrecan were measured by real-time PCR. RESULTS: No differences
      between the two homogenisation methods were found. RNA isolation using the RNeasy
      Fibrous and Lipid kits resulted in the purest RNA (A260/A280 ratio), whereas
      TRIzol isolations resulted in RNA that is not as pure, and show a larger
      difference in gene expression of duplicate samples compared with both RNeasy
      kits. The Aurum kit showed low reproducibility. CONCLUSION: For the extraction of
      high-quality RNA from cartilaginous structures, we suggest homogenisation of the
      samples by the MagNA Lyser. For AC, NP and AF we recommend the RNeasy Fibrous
      kit, whereas for the meniscus the RNeasy Lipid kit is advised.Cite this article:
      M. Peeters, C. L. Huang, L. A. Vonk, Z. F. Lu, R. A. Bank, M. N. Helder, B.
      Zandieh Doulabi. Optimisation of high-quality total ribonucleic acid isolation
      from cartilaginous tissues for real-time polymerase chain reaction analysis. Bone
      Joint Res 2016;5:560-568. DOI: 10.1302/2046-3758.511.BJR-2016-0033.R3.

PMID- 27881440
TI  - Culturing bone marrow cells with dexamethasone and ascorbic acid improves
      osteogenic cell sheet structure.
AB  - OBJECTIVES: To assess the structure and extracellular matrix molecule expression
      of osteogenic cell sheets created via culture in medium with both dexamethasone
      (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone.
      METHODS: Osteogenic cell sheets were prepared by culturing rat bone marrow
      stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex,
      and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA
      expression were assessed in vitro, and the appearance of the cell sheets was
      observed after mechanical retrieval using a scraper. beta-tricalcium phosphate
      (beta-TCP) was then wrapped with the cell sheets from the four different groups
      and subcutaneously implanted into rats. RESULTS: After mechanical retrieval, the
      osteogenic cell sheets from the MEM, MEM with AscP, and MEM with Dex groups
      appeared to be fragmented or incomplete structures. The cell sheets cultured with
      Dex/AscP remained intact after mechanical retrieval, without any identifiable
      tears. Culture with Dex/AscP increased the mRNA and protein expression of
      extracellular matrix proteins and cell number compared with those of the other
      three groups. More bridging bone formation was observed after transplantation of
      the beta-TCP scaffold wrapped with cell sheets cultured with Dex/AscP, than in
      the other groups. CONCLUSIONS: These results suggest that culture with Dex/AscP
      improves the mechanical integrity of the osteogenic cell sheets, allowing
      retrieval of the confluent cells in a single cell sheet structure. This method
      may be beneficial when applied in cases of difficult tissue reconstruction, such
      as nonunion, bone defects, and osteonecrosis.Cite this article: M. Akahane, T.
      Shimizu, T. Kira, T. Onishi, Y. Uchihara, T. Imamura, Y. Tanaka. Culturing bone
      marrow cells with dexamethasone and ascorbic acid improves osteogenic cell sheet
      structure. Bone Joint Res 2016;5:569-576. DOI: 10.1302/2046-3758.511.BJR-2016
      0013.R1.

PMID- 27881441
TI  - Evaluation of the histological and mechanical features of tendon healing in a
      rabbit model with the use of second-harmonic-generation imaging and tensile
      testing.
AB  - OBJECTIVES: This study aimed to evaluate the histological and mechanical features
      of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging
      and tensile testing. MATERIALS AND METHODS: A total of eight male Japanese white
      rabbits were used for this study. The flexor digitorum tendons in their right leg
      were sharply transected, and then were repaired by intratendinous stitching. At
      four weeks post-operatively, the rabbits were killed and the flexor digitorum
      tendons in both right and left legs were excised and used as specimens for tendon
      healing (n = 8) and control (n = 8), respectively. Each specimen was examined by
      SHG imaging, followed by tensile testing, and the results of the two testing
      modalities were assessed for correlation. RESULTS: While the SHG light intensity
      of the healing tendon samples was significantly lower than that of the uninjured
      tendon samples, 2D Fourier transform SHG images showed a clear difference in
      collagen fibre structure between the uninjured and the healing samples, and among
      the healing samples. The mean intensity of the SHG image showed a moderate
      correlation (R2 = 0.37) with Young's modulus obtained from the tensile testing.
      CONCLUSION: Our results indicate that SHG microscopy may be a potential indicator
      of tendon healing.Cite this article: E. Hase, K. Sato, D. Yonekura, T.
      Minamikawa, M. Takahashi, T. Yasui. Evaluation of the histological and mechanical
      features of tendon healing in a rabbit model with the use of second-harmonic
      generation imaging and tensile testing. Bone Joint Res 2016;5:577-585. DOI:
      10.1302/2046-3758.511.BJR-2016-0162.R1.

PMID- 27881442
TI  - Saturated fat and heart disease.

PMID- 27881443
TI  - Exploitation of EP300 and CREBBP Lysine Acetyltransferases by Cancer.
AB  - p300 and CREB-binding protein (CBP), two homologous lysine acetyltransferases in
      metazoans, have a myriad of cellular functions. They exert their influence mainly
      through their roles as transcriptional regulators but also via nontranscriptional
      effects inside and outside of the nucleus on processes such as DNA replication
      and metabolism. The versatility of p300/CBP as molecular tools has led to their
      exploitation by viral oncogenes for cellular transformation and by cancer cells
      to achieve and maintain an oncogenic phenotype. How cancer cells use p300/CBP in
      their favor varies depending on the cellular context and is evident by the
      growing list of loss- and gain-of-function genetic alterations in p300 and CBP in
      solid tumors and hematological malignancies. Here, we discuss the biological
      functions of p300/CBP and how disruption of these functions by mutations and
      alterations in expression or subcellular localization contributes to the cancer
      phenotype.

PMID- 27881444
TI  - The Regulation of Cellular Functions by the p53 Protein: Cellular Senescence.
AB  - Transformed cells have properties that allow them to survive and proliferate
      inappropriately. These characteristics often arise as a result of mutations
      caused by DNA damage. p53 suppresses transformation by removing the proliferative
      or survival capacity of cells with DNA damage or inappropriate cell-cycle
      progression. Cellular senescence, marked by morphological and gene expression
      changes, is a critical component of p53-mediated tumor suppression. In response
      to stress, p53 can facilitate an arrest and senescence program in cells exposed
      to stresses such as DNA damage and oncogene activation, preventing
      transformation. Senescent cells are evident in precancerous adenoma-type lesions,
      whereas proliferating, malignant tumors have bypassed senescence, either by p53
      mutation or inactivation of the p53 pathway by other means. Tumors that have
      retained wild-type p53 often show a p53-mediated senescence response to
      chemotherapy. This response is actually detrimental in some tumor types, as
      senescent cells can drive relapse by persisting and producing cytokines and
      chemokines through an acquired secretory phenotype.

PMID- 27881445
TI  - Fostering 21st-Century Evolutionary Reasoning: Teaching Tree Thinking to
      Introductory Biology Students.
AB  - The ability to interpret and reason from Tree of Life (ToL) diagrams has become a
      vital component of science literacy in the 21st century. This article reports on
      the effectiveness of a research-based curriculum, including an instructional
      booklet, laboratory, and lectures, to teach the fundamentals of such tree
      thinking in an introductory biology class for science majors. We present the
      results of a study involving 117 undergraduates who received either our new
      research-based tree-thinking curriculum or business-as-usual instruction. We
      found greater gains in tree-thinking abilities for the experimental instruction
      group than for the business-as-usual group, as measured by performance on our
      novel assessment instrument. This was a medium size effect. These gains were
      observed on an unannounced test that was administered ~5-6 weeks after the
      primary instruction in tree thinking. The nature of students' postinstruction
      difficulties with tree thinking suggests that the critical underlying concept for
      acquiring expert-level competence in this area is understanding that any specific
      phylogenetic tree is a subset of the complete, unimaginably large ToL.

PMID- 27881446
TI  - Practical Strategies for Collaboration across Discipline-Based Education Research
      and the Learning Sciences.
AB  - Rather than pursue questions related to learning in biology from separate camps,
      recent calls highlight the necessity of interdisciplinary research agendas.
      Interdisciplinary collaborations allow for a complicated and expanded approach to
      questions about learning within specific science domains, such as biology.
      Despite its benefits, interdisciplinary work inevitably involves challenges. Some
      such challenges originate from differences in theoretical and methodological
      approaches across lines of work. Thus, aims at developing successful
      interdisciplinary research programs raise important considerations regarding
      methodologies for studying biology learning, strategies for approaching
      collaborations, and training of early-career scientists. Our goal here is to
      describe two fields important to understanding learning in biology, discipline
      based education research and the learning sciences. We discuss differences
      between each discipline's approach to biology education research and the benefits
      and challenges associated with incorporating these perspectives in a single
      research program. We then propose strategies for building productive
      interdisciplinary collaboration.

PMID- 27881447
TI  - CMKLR1 activation ex vivo does not increase proportionally to serum total
      chemerin in obese humans.
AB  - Prochemerin is the inactive precursor of the adipokine chemerin. Proteolytic
      processing is obligatory for the conversion of prochemerin into active chemerin
      and subsequent regulation of cellular processes via the chemokine-like receptor 1
      (CMKLR1). Elevated plasma or serum chemerin concentrations and differential
      processing of prochemerin have been reported in obese humans. The impact of these
      changes on CMKLR1 signalling in humans is unknown. The objective of this pilot
      study was to develop a cellular bioassay to measure CMKLR1 activation by chemerin
      present in human serum and to characterise how obesity modifies serum activation
      of CMKLR1 under fasted and fed conditions. Blood samples were collected from
      control (N = 4, BMI 20-25) and obese (N = 4, BMI >30) female subjects after an
      overnight fast (n = 2) and at regular intervals (n = 7) following consumption of
      breakfast over a period of 6 h. A cellular CMKLR1-luminescent reporter assay and
      a pan-chemerin ELISA were used to determine CMKLR1 activation and total chemerin
      concentrations, respectively. Serum total chemerin concentration (averaged across
      all samples) was higher in obese vs control subjects (17.9 +/- 1.8 vs 10.9 +/-
      0.5 nM, P < 0.05), but serum activation of CMKLR1 was similar in both groups. The
      CMKLR1 activation/total chemerin ratio was lower in obese vs control subjects
      (0.33 +/- 0.04 vs 0.58 +/- 0.05, P < 0.05). After breakfast, serum total chemerin
      or CMKLR1 activation did not differ from baseline values. In conclusion, the
      unexpected observation that obese serum activation of CMKLR1 did not match
      increased total chemerin concentrations suggests impaired processing to and/or
      enhanced degradation of active chemerin in serum of obese humans.

PMID- 27881448
TI  - Prion-Like Polymerization in Immunity and Inflammation.
AB  - The innate immune system relies on receptors that sense common signs of infection
      to trigger a robust host-defense response. Receptors such as RIG-I and NLRP3
      activate downstream adaptors mitochondrial antiviral signaling (MAVS) and
      apoptosis-associated speck-like protein (ASC), respectively, to propagate immune
      and inflammatory signaling. Recent studies have indicated that both MAVS and ASC
      form functional prion-like polymers to propagate immune signaling. Here, we
      summarize the biochemical, genetic, and structural studies that characterize the
      prion-like behavior of MAVS and ASC in their respective signaling pathways. We
      then discuss prion-like polymerization as an evolutionarily conserved mechanism
      of signal transduction in innate immunity in light of the similarity between the
      NLRP3-ASC, the NLRP3-ASC pathway in mammals, and the NWD2-HET-s pathway in fungi.
      We conclude by outlining the unique advantages to signaling through functional
      prions and potential future directions in the field.

PMID- 27881450
TI  - Glial Fibrillary Acidic Protein Serum Levels Distinguish between Intracerebral
      Hemorrhage and Cerebral Ischemia in the Early Phase of Stroke.
AB  - BACKGROUND: Recent studies have suggested that glial fibrillary acidic protein
      (GFAP) serum concentrations distinguish between intracerebral hemorrhage (ICH)
      and ischemic stroke (IS) shortly after symptom onset. In this prospective
      multicenter trial we validated GFAP in an independent patient cohort and assessed
      the quantitative relationship between GFAP release, bleeding size, and
      localization. METHODS: We included patients with a persistent neurological
      deficit (NIH Stroke Scale >=4) suggestive of stroke within 6 h of symptom onset.
      Blood samples were drawn at hospital admission. GFAP serum concentrations were
      measured using an electrochemiluminometric immunoassay. Primary endpoint was the
      final diagnosis established at hospital discharge (ICH, IS, or stroke mimic).
      RESULTS: 202 patients were included (45 with ICH, 146 with IS, 11 stroke mimics).
      GFAP concentrations were significantly higher in ICH than in IS patients [median
      (interquartile range) 0.16 MUg/L (0.04-3.27) vs 0.01 MUg/L (0.01-0.01), P
      <0.001]. A GFAP cutoff of 0.03 MUg/L provided a sensitivity of 77.8% and a
      specificity of 94.2% in distinguishing ICH from IS and stroke mimics [ROC
      analysis area under the curve 0.872 (95% CI, 0.802-0.942), P <0.001]. GFAP serum
      concentrations were positively correlated with ICH volume. Lobar ICH volumes were
      larger and thus associated with higher GFAP concentrations as compared to deep
      ICH. CONCLUSIONS: Serum GFAP was confirmed to be a biomarker indicating ICH in
      patients presenting with acute stroke symptoms. Very small ICH may be missed
      owing to less tissue destruction.

PMID- 27881451
TI  - Demystifying HDL Cholesterol-A "Human Knockout" to the Rescue?

PMID- 27881456
TI  - An older man with thoracic back pain.

PMID- 27881457
TI  - Voluntary euthanasia deaths in Quebec outstrip predictions by three to one.

PMID- 27881449
TI  - Primary Cilia and Mammalian Hedgehog Signaling.
AB  - It has been a decade since it was discovered that primary cilia have an essential
      role in Hedgehog (Hh) signaling in mammals. This discovery came from screens in
      the mouse that identified a set of genes that are required for both normal Hh
      signaling and for the formation of primary cilia. Since then, dozens of mouse
      mutations have been identified that disrupt cilia in a variety of ways and have
      complex effects on Hedgehog signaling. Here, we summarize the genetic and
      developmental studies used to deduce how Hedgehog signal transduction is linked
      to cilia and the complex effects that perturbation of cilia structure can have on
      Hh signaling. We conclude by describing the current status of our understanding
      of the cell-type-specific regulation of ciliogenesis and how that determines the
      ability of cells to respond to Hedgehog ligands.

PMID- 27881458
TI  - Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year
      randomized controlled clinical trial.
AB  - OBJECTIVE: Reduced bone mineral density (BMD) is seen in Turner syndrome (TS)
      with an increased risk of fractures, and body composition is characterized by
      increased body fat and decreased lean body mass. To evaluate the effect of two
      different doses of oral 17B-estradiol in young TS women on bone mineral density
      (BMD), biochemical markers of bone turnover and body composition with the
      hypothesis of a positive effect of the higher dose. DESIGN: A double-blind 5-year
      randomized controlled clinical trial. 20 young TS women participated. Inclusion
      criteria were diagnosis of TS, age 15-25 years and current treatment with 2 mg
      oral estradiol daily. METHODS: The low-dose (LD) group was administered 2 mg 17B
      estradiol/day orally and placebo, the high-dose (HD) group was administered 2 + 2
      mg 17B-estradiol/day orally. Main outcome measures were whole body and regional
      bone mineral density (BMD), lean body mass (LBM), fat mass (FM) measured yearly
      by DXA scan and resorptive and formative bone markers in serum. RESULTS: BMD,
      whole body and regional, increased over time with an attenuation toward the end
      of the study, and bone turnover markers decreased over time, both with no
      differences between the treatment groups (P = 0.2-0.9). LBM increased
      significantly more in the HD group (P = 0.02). FM remained stable in both groups.
      CONCLUSIONS: A steady increase in BMD over time in TS was found similar to
      healthy young women. The higher estrogen dose did not differentially affect BMD
      or bone markers. The positive effect on body composition may have long-ranging
      health benefits in TS.

PMID- 27881459
TI  - A typical sign on a plain knee radiograph.

PMID- 27881460
TI  - Plans for improving care are being derailed by hospital deficits, GP leader
      warns.

PMID- 27881462
TI  - Seven day service policy lacked transparency, review concludes.

PMID- 27881461
TI  - Lysosomal dysfunction disrupts presynaptic maintenance and restoration of
      presynaptic function prevents neurodegeneration in lysosomal storage diseases.
AB  - Lysosomal storage disorders (LSDs) are inherited diseases characterized by
      lysosomal dysfunction and often showing a neurodegenerative course. There is no
      cure to treat the central nervous system in LSDs. Moreover, the mechanisms
      driving neuronal degeneration in these pathological conditions remain largely
      unknown. By studying mouse models of LSDs, we found that neurodegeneration
      develops progressively with profound alterations in presynaptic structure and
      function. In these models, impaired lysosomal activity causes massive perikaryal
      accumulation of insoluble alpha-synuclein and increased proteasomal degradation
      of cysteine string protein alpha (CSPalpha). As a result, the availability of
      both alpha-synuclein and CSPalpha at nerve terminals strongly decreases, thus
      inhibiting soluble NSF attachment receptor (SNARE) complex assembly and synaptic
      vesicle recycling. Aberrant presynaptic SNARE phenotype is recapitulated in mice
      with genetic ablation of one allele of both CSPalpha and alpha-synuclein. The
      overexpression of CSPalpha in the brain of a mouse model of mucopolysaccharidosis
      type IIIA, a severe form of LSD, efficiently re-established SNARE complex
      assembly, thereby ameliorating presynaptic function, attenuating
      neurodegenerative signs, and prolonging survival. Our data show that
      neurodegenerative processes associated with lysosomal dysfunction may be
      presynaptically initiated by a concomitant reduction in alpha-synuclein and
      CSPalpha levels at nerve terminals. They also demonstrate that neurodegeneration
      in LSDs can be slowed down by re-establishing presynaptic functions, thus
      identifying synapse maintenance as a novel potentially druggable target for brain
      treatment in LSDs.

PMID- 27881466
TI  - Caloric restriction improves health-related quality of life in healthy normal
      weight and overweight individuals.

PMID- 27881467
TI  - EU to launch new antimicrobial resistance action plan.

PMID- 27881463
TI  - Sestrin-3 modulation is essential for therapeutic efficacy of cucurbitacin B in
      lung cancer cells.
AB  - Many purified compounds from dietary sources have been investigated for their
      anticancer activities. The main issue with most agents is their effectiveness at
      high doses which generally could not be delivered to humans through dietary
      consumption. Here, we observed that cucurbitacin B, a tetracyclic triterpenoid
      present in pumpkins, gourds and squashes, exhibits antiproliferative effects on
      human non-small cell lung cancer (NSCLC) cells at nanomolar concentrations.
      Treatment with cucurbitacin B (0.2-0.6 MUM; 24 h) was found to result in decrease
      in the viability of EGFR-wild type (A549 and H1792) and EGFR-mutant lung cancer
      cells (H1650 and H1975) and reduction in cell-colonies but had only minimal
      effect on normal human bronchial epithelial cells. Treatment with cucurbitacin B
      also caused inhibition of PI3K/mTOR and signal transducer and activator of
      transcription (STAT)-3 signaling along with simultaneous activation of AMPKalpha
      levels in both EGFR-wild type and EGFR-mutant lung cancer cells. Cucurbitacin B
      caused specific increase in the protein and mRNA expression of sestrin-3 in EGFR
      mutant lung cancer cells, but not in EGFR-wild type cells. Treatment with
      cucurbitacin B to sestrin-3 siRNA treated EGFR-mutant cells further amplified the
      decrease in cell-viability and caused more sustained G2-phase cell cycle arrest,
      suggesting that these effects are mediated partly through sestrin-3. We also
      found that sestrin-3 has a role in the induction of apoptosis by cucurbitacin B
      in both EGFR-wild type and EGFR-mutant lung cancer cells. These findings suggest
      novel mechanism by the modulation of sestrin-3 for the action of cucurbitacin B
      and suggest that it could be developed as an agent for therapy of NSCLC.

PMID- 27881468
TI  - Elevated ambient temperatures and risk of neural tube defects.
AB  - OBJECTIVES: The association between ambient heat and neural tube defects has
      received limited attention, despite imminent climate warming this century. We
      sought to determine the relationship between elevated outdoor temperatures during
      neurogenesis and risk of neural tube defects. METHODS: We carried out a
      retrospective cohort study of 887 710 fetuses between 3 and 4 weeks
      postconception from the months of April through September for 1988-2012 in
      Quebec, Canada. The exposure was maximum daily temperature and the outcome
      presence of neural tube defects at delivery. We estimated prevalence ratios (PR)
      and 95% CIs for the association between maximum temperature and neural tube
      defects in log-binomial regression models adjusted for maternal characteristics.
      RESULTS: Relative to 20 degrees C, exposure to temperatures of 30 degrees C was
      associated with risk of neural tube defects on day 5 (PR 1.56, 95% CI 1.04 to
      2.35) and day 6 (PR 1.49, 95% CI 1.00 to 2.21) of the 4th week postconception,
      during the time of neural tube closure. The trend was apparent for spina bifida
      and anencephalus/encephalocoele, the main subtypes of neural tube defects.
      Temperature during the 3rd week postconception was not associated with neural
      tube defects. CONCLUSIONS: Elevated ambient temperatures may be weakly associated
      with risk of neural tube defects during tube closure.

PMID- 27881469
TI  - The role of intersection and street design on severity of bicycle-motor vehicle
      crashes.
AB  - BACKGROUND: Safety concerns are a major barrier to cycling. Intersection and
      street design variables such as intersection angles and street width might
      contribute to the severity of crashes and the safety concerns. In this study we
      examined whether these design variables were associated with bicycle-motor
      vehicle crashes (BMVC) severity. METHODS: Using the geographical information
      system and latitudes/longitudes recorded by the police using a global positioning
      device, we extracted intersection angles, street width, bicycle facilities,
      posted speed limits and annual average daily traffic from 3266 BMVC data from New
      York City police records. Additional variables about BMVC, including age and sex
      of the bicyclist, time of the day, road surface conditions, road character,
      vehicle type and injury severity, were obtained from police reports. Injury
      severity was classified as severe (incapacitating or killed) or non-severe (non
      incapacitating, possible injury). The associations between injury severity and
      environment design variables were examined using multivariate log-binomial
      regression model. FINDINGS: Compared with crashes at orthogonal intersections,
      crashes at non-orthogonal intersections had 1.37 times (95% CI 1.05 to 1.80) and
      non-intersection street segments had 1.31 times (95% CI 1.01 to 1.70) higher risk
      of a severe injury. Crashes that involved a truck or a bus were twice as likely
      to result in a severe injury outcome; street width was not significantly
      associated with injury severity. CONCLUSION: Crashes at non-orthogonal
      intersections and non-intersection segments are more likely to result in higher
      injury severity. The findings can be used to improve road design and develop
      effective safety interventions.

PMID- 27881470
TI  - Modelling primary blast lung injury: current capability and future direction.
AB  - Primary blast lung injury frequently complicates military conflict and terrorist
      attacks on civilian populations. The fact that it occurs in areas of conflict or
      unpredictable mass casualty events makes clinical study in human casualties
      implausible. Research in this field is therefore reliant on the use of some form
      of biological or non-biological surrogate model. This article briefly reviews the
      modelling work undertaken in this field until now and describes the rationale
      behind the generation of an in silico physiological model.

PMID- 27881471
TI  - Selection Limits to Adaptive Walks on Correlated Landscapes.
AB  - Adaptation depends critically on the effects of new mutations and their
      dependency on the genetic background in which they occur. These two factors can
      be summarized by the fitness landscape. However, it would require testing all
      mutations in all backgrounds, making the definition and analysis of fitness
      landscapes mostly inaccessible. Instead of postulating a particular fitness
      landscape, we address this problem by considering general classes of landscapes
      and calculating an upper limit for the time it takes for a population to reach a
      fitness peak, circumventing the need to have full knowledge about the fitness
      landscape. We analyze populations in the weak-mutation regime and characterize
      the conditions that enable them to quickly reach the fitness peak as a function
      of the number of sites under selection. We show that for additive landscapes
      there is a critical selection strength enabling populations to reach high-fitness
      genotypes, regardless of the distribution of effects. This threshold scales with
      the number of sites under selection, effectively setting a limit to adaptation,
      and results from the inevitable increase in deleterious mutational pressure as
      the population adapts in a space of discrete genotypes. Furthermore, we show that
      for the class of all unimodal landscapes this condition is sufficient but not
      necessary for rapid adaptation, as in some highly epistatic landscapes the
      critical strength does not depend on the number of sites under selection;
      effectively removing this barrier to adaptation.

PMID- 27881472
TI  - An Unexpected Regulatory Cascade Governs a Core Function of the Drosophila PRC1
      Chromatin Protein Su(z)2.
AB  - Polycomb group (PcG) proteins are major chromatin-bound factors that can read and
      modify chromatin states to maintain gene silencing throughout development. Here
      we focus on a close homolog of the PcG protein Posterior sex combs to better
      understand how these proteins affect regulation. This homolog, called Suppressor
      2 of zeste [Su(z)2] is composed of two regions: the N-terminal homology region
      (HR), which serves as a hub for protein interactions, and the C-terminal region
      (CTR), which is believed to harbor the core activity of compacting chromatin.
      Here, we describe our classical genetic studies to dissect the structure of
      Su(z)2 Surprisingly, we found that the CTR is dispensable for viability.
      Furthermore, the core activity of Su(z)2 seems to reside in the HR instead of the
      CTR. Remarkably, our data also suggest a regulatory cascade between CTR and HR of
      Su(z)2, which, in turn, may help prioritize the myriad of PcG interactions that
      occur with the HR.

PMID- 27881473
TI  - Clinicopathological features of neoplasms with neuroendocrine differentiation
      occurring in the liver.
AB  - BACKGROUND/AIMS: We investigated the clinicopathological features of hepatic
      neuroendocrine tumours (NET) and neuroendocrine carcinoma (NEC), which remain
      largely unknown. MATERIAL AND METHODS: We examined 1235 tumours from 1048
      patients who had undergone curative hepatectomy for liver neoplasms at Kurume
      University Hospital. Pathological diagnoses were based on the 2010 WHO
      Classification of Tumours of the Digestive System. We performed immunostaining
      for hepatocyte markers (eg, hepatocyte paraffin (HepPar)-1), neuroendocrine
      markers (eg, chromogranin A (CGA)) and the proliferation marker (Ki-67). RESULTS:
      There were four cases of NET G2 (0.38%) and five of hepatic malignant tumours
      with an NEC component (HNEC) (0.48%). HNEC cases were classified into three
      types, that is, transitional, intermediate and separate types, according to their
      histological and immunohistochemical features. In the former two types, the NEC
      component intermingled with the moderately to poorly differentiated
      hepatocellular carcinoma (HCC) component or intermediate component consisting of
      tumour cells showing the colocalisation of CGA and HepPar-1. In the separate
      type, the NEC and poorly differentiated HCC components were present separately,
      whereas the sarcomatous HCC component was detected in the vicinity of the NEC
      component. Ki-67 labelling indices of the NET G2, HCC and NEC components of HNEC
      were 6.8%, 14.9% and 58.9%, respectively. CONCLUSIONS: Primary hepatic NET and
      NEC are very rare tumours. The NEC component in HNEC showed high proliferative
      activity and influenced patient prognoses.

PMID- 27881475
TI  - United we stand: big roles for small RNA gene clusters.
AB  - Prokaryotes and eukaryotes evolved relatively similar RNA-based molecular
      mechanisms to fight potentially deleterious nucleic acids coming from phages,
      transposons, or viruses. Short RNAs guide effector complexes toward their targets
      to be silenced or eliminated. These short immunity RNAs are transcribed from
      clustered loci. Unexpectedly and strikingly, bacterial and eukaryotic immunity
      RNA clusters share substantial functional and mechanistic resemblances in
      fighting nucleic acid intruders.

PMID- 27881474
TI  - Cancer Secretome May Influence BSP and DSP Expression in Human Salivary Gland
      Cells.
AB  - One of the biggest challenges in managing head and neck cancers, especially
      salivary gland cancers, is the identification of secreted biomarkers of the
      disease that can be evaluated noninvasively. A relevant source of enriched tumor
      markers could potentially be found in the tumor secretome. Although numerous
      studies have evaluated secretomes from various cancers, the influence of the
      cancer secretome derived from salivary gland cancers on the behavior of normal
      cells has not yet been elucidated. Our data indicate that secretome derived from
      salivary gland cancer cells can influence the expression of two potential
      biomarkers of oral cancer-namely, bone sialoprotein (BSP) and dentin sialoprotein
      (DSP)-in normal salivary gland cells. Using routine immunohistochemistry,
      immunofluorescence, and immunoblotting techniques, we demonstrate an enrichment
      of BSP and DSP in human salivary gland (HSG) cancer tissue, unique localizations
      of BSP and DSP in HSG cancer cells, and enriched expression of BSP and DSP in
      normal salivary gland cells exposed to a cancer secretome. The secretome domain
      of the cancer microenvironment could alter signaling cascades responsible for
      normal cell proliferation, migration, and invasion, thus enhancing cancer cell
      survival and the potential for cancer progression. The cancer secretome may be
      critical in maintaining and stimulating "cancer-ness," thus potentially promoting
      specific hallmarks of metastasis.

PMID- 27881477
TI  - Reconsidering the "Asphalt Identikit".
AB  - Background/Aim The "asphalt identikit" theory suggests that driving cessation
      inevitably leads to feelings of incompetence and dependency. This article
      challenges this proposition by investigating the driving-related possible selves
      of British older adults living in West London. Methods Thematic analysis of data
      from 19 of 39 interviews in which older adults participating in a larger study
      talked about driving in the context of their grocery shopping. Results Three
      themes were evident: "I can drive - that makes a huge difference," "Expecting to
      lose my license," and "I gave up my license." Discussion Driving cessation is not
      a dreaded possible self for all older adults. Older adults may use a variety of
      identity maintenance processes to retain their positive sense of self.
      Conclusions Mental well-being can be maintained during driving cessation by
      finding ways to compensate for the loss of a license and finding alternative ways
      of achieving hoped-for possible selves.

PMID- 27881476
TI  - Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels
      positively and negatively.
AB  - Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation
      and degradation of their precursors by terminal uridylyltransferases TUT4/7 and
      3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a
      also controls the production of neuro-specific miRNA-9 via a polyuridylation
      independent mechanism. Here we reveal that the sequences and structural
      characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of
      binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production.
      Finally, we show that the constitutive expression of untagged Lin28a during
      neuronal differentiation in vitro positively and negatively affects numerous
      other miRNAs. Our findings shed light on the role of Lin28a in differentiating
      cells and on the ways in which one RNA-binding protein can perform multiple roles
      in the regulation of RNA processing.

PMID- 27881480
TI  - Generation of Signs Within Semantic and Phonological Categories: Data from Deaf
      Adults and Children Who Use American Sign Language.
AB  - Two key areas of language development include semantic and phonological
      knowledge. Semantic knowledge relates to word and concept knowledge. Phonological
      knowledge relates to how language parameters combine to create meaning. We
      investigated signing deaf adults' and children's semantic and phonological sign
      generation via one-minute tasks, including animals, foods, and specific
      handshapes. We investigated the effects of chronological age, age of sign
      language acquisition/years at school site, gender, presence of a disability, and
      geographical location (i.e., USA and Puerto Rico) on participants' performance
      and relations among tasks. In general, the phonological task appeared more
      difficult than the semantic tasks, students generated more animals than foods,
      age, and semantic performance correlated for the larger sample of U.S. students,
      and geographical variation included use of fingerspelling and specific signs.
      Compared to their peers, deaf students with disabilities generated fewer semantic
      items. These results provide an initial snapshot of students' semantic and
      phonological sign generation.

PMID- 27881479
TI  - Barriers and Facilitators to Deaf Trauma Survivors' Help-Seeking Behavior:
      Lessons for Behavioral Clinical Trials Research.
AB  - Deaf individuals experience significant obstacles to participating in behavioral
      health research when careful consideration is not given to accessibility during
      the design of study methodology. To inform such considerations, we conducted an
      exploratory secondary analysis of a mixed-methods study that originally explored
      16 Deaf trauma survivors' help-seeking experiences. Our objective was to identify
      key findings and qualitative themes from consumers' own words that could be
      applied to the design of behavioral clinical trials methodology. In many ways,
      the themes that emerged were not wholly dissimilar from the general preferences
      of members of other sociolinguistic minority groups-a need for communication
      access, empathy, respect, strict confidentiality procedures, trust, and
      transparency of the research process. Yet, how these themes are applied to the
      inclusion of Deaf research participants is distinct from any other
      sociolinguistic minority population, given Deaf people's unique sensory and
      linguistic characteristics. We summarize our findings in a preliminary "Checklist
      for Designing Deaf Behavioral Clinical Trials" to operationalize the steps
      researchers can take to apply Deaf-friendly approaches in their empirical work.

PMID- 27881481
TI  - Emotion Understanding in Preschool Children with Mild-to-Severe Hearing Loss.
AB  - Deaf and hard of hearing school-aged children are at risk for delayed development
      of emotion understanding; however, little is known about this during the
      preschool years. We compared the level of emotion understanding in a group of 35
      4-5-year-old children who use hearing aids to that of 130 children with typical
      hearing. Moreover, we investigated the parents' perception of their child's level
      of emotion understanding. Children were assessed with the Test of Emotion
      Comprehension. Parents were presented with the same test and asked to guess what
      their child answered on each item. The results showed that children with hearing
      loss performed at the same level as typically hearing children, despite having
      lower vocabulary scores. Parents of children with hearing loss were more accurate
      in their estimations of their child's competence, and higher accuracy was
      associated with better emotion understanding. These findings may have
      implications for early intervention planning.

PMID- 27881482
TI  - The Significance of Deaf Identity for Psychological Well-Being.
AB  - Research has paid attention to how deaf identity affects life outcomes such as
      psychological well-being. However, studies are often carried out with small
      samples and without controlling for other variables. This study examined how
      different forms of identity-deaf, hearing, bicultural (deaf and hearing), and
      marginal (neither deaf nor hearing)-were associated with levels of psychological
      well-being and a number of other variables. The sample was 742 adults with
      hearing loss in Denmark. The study found that those with a deaf, hearing or
      bicultural identity had significantly higher levels of psychological well-being
      than those with a marginal identity. Further, it found that additional
      disability, educational level, and feeling discriminated against significantly
      and independently explained the degree of psychological well-being. Results are
      discussed here with respect to social identity theory and current deaf identity
      themes.

PMID- 27881483
TI  - Preliminary Evidence Assessing Social-Emotional Competences in Deaf and Hard of
      Hearing Infants and Toddlers Using a New Parent Questionnaire.
AB  - Social-emotional competences are an important developmental domain for deaf and
      hard of hearing (DHH) children and early diagnosis of problems is needed to
      ensure that DHH children receive appropriate support in this domain. In order to
      explore the usefulness of an instrument, which was recently developed for very
      young children, two studies in DHH infants and toddlers were conducted from
      Germany using the Social-Emotional Assessment/Evaluation Measure (Squires et al.
      (2013). Social-Emotional Assessment/Evaluation Measure (SEAM). Baltimore, ML:
      Brooks). Preliminary analysis of data obtained from a sample of 182 DHH children
      aged between 2 and 36 months (Study 1) suggests that it provides valid, reliable
      data and is suitable for use in practice. The data also corroborate well-known
      findings from other research in deaf education, in particular the role of
      parental responsivity for the development of social-emotional competences. Study
      2 documents the consistency of evaluations of 44 DHH children by their mothers
      and by early intervention providers using the scales. Overall, the results
      suggest that this new evaluation instrument has potential applications in deaf
      educational practice but further research is needed to demonstrate its full
      value.

PMID- 27881484
TI  - Cell-penetrating peptides recruit type A scavenger receptors to the plasma
      membrane for cellular delivery of nucleic acids.
AB  - Scavenger receptors (SRs) are a large family of multifunctional receptors that
      are involved in a range of physiologic and pathologic processes. The ability of
      class A scavenger receptors (SR-As) to bind anionic ligands facilitates the
      internalization of negatively charged cell-penetrating peptide (CPP)-nucleic acid
      nanocomplexes and thus makes them attractive targets for delivery of various
      nucleic acids. Recently, we demonstrated that SR-A3 and SR-A5 are recruited from
      intracellular membranes to the plasma membrane after incubation with PepFect 14
      splice-switching oligonucleotide complexes. Here, we examined the mechanisms
      responsible for translocation of SR-As to the cell surface. We demonstrate that,
      in addition to nanocomplexes, some amphipathic CPPs are able to induce
      externalization of SR-A3 and SR-A5, and this process requires the presence of
      calcium ions. Furthermore, translocation of SR-A3 and SR-A5 requires activity of
      phosphatidylinositol-3-kinase, intact actin cytoskeleton, and the presence of
      serum proteins in culture medium.-Juks, C., Lorents, A., Arukuusk, P., Langel,
      U., Pooga, M. Cell-penetrating peptides recruit type A scavenger receptors to the
      plasma membrane for cellular delivery of nucleic acids.

PMID- 27881485
TI  - Visualization of ligand-induced Gi-protein activation in chemotaxing cells.
AB  - Cell migration to chemoattractants is critically important in both normal
      physiology and the pathogenesis of many diseases. In GPCR-mediated chemotaxis,
      GPCRs transduce the gradient of an extracellular chemotactic ligand into
      intracellular responses via the activation of heterotrimeric G proteins. However,
      ligand-induced G-protein activation has not been directly imaged as yet in
      mammalian chemotaxing cells. We developed a Forster resonance energy transfer
      (FRET) probe, R10-Gi, by linking the Gi-protein alpha subunit to the regulator of
      G-protein signaling domain. The R10-Gi probe was coupled with a chemoattractant
      leukotriene B4 (LTB4) receptor 1 (BLT1) that induced the receptor to display a
      high-affinity ligand binding activity (Kd = 0.91 nM) in HEK293 cells. The R10-Gi
      probe exhibited an increased FRET signal in accord with the LTB4-dependent
      activation of Gi Furthermore, neutrophil-like differentiated human leukemia cell
      line 60 that expressed the intrinsic BLT1 displayed temporal Gi-protein
      activation in an area localized to the leading edge during chemotaxis in a
      shallow gradient of LTB4 These findings afford an opportunity to clarify the
      mechanisms underlying the subcellular regulation of Gi-protein activity, as well
      as GPCR-mediated ligand sensing, during chemotaxis in mammalian cells.-Masuda,
      K., Kitakami, J., Kozasa, T., Kodama, T., Ihara, S., Hamakubo, T. Visualization
      of ligand-induced Gi-protein activation in chemotaxing cells.

PMID- 27881486
TI  - Lysine 63 ubiquitination is involved in the progression of tubular damage in
      diabetic nephropathy.
AB  - The purpose of our study was to evaluate how hyperglycemia (HG) influences Lys63
      protein ubiquitination and its involvement in tubular damage and fibrosis in
      diabetic nephropathy (DN). Gene and protein expression of UBE2v1, a ubiquitin
      conjugating E2-enzyme variant that mediates Lys63-linked ubiquitination, and
      Lys63-ubiquitinated proteins increased in HK2 tubular cells under HG. Matrix
      assisted laser desorption/ionization-time of flight/tandem mass spectrometry
      identified 30 Lys63-ubiquitinated proteins, mainly involved in cellular
      organization, such as beta-actin, whose Lys63 ubiquitination increased under HG,
      leading to cytoskeleton disorganization. This effect was reversed by the
      inhibitor of the Ubc13/UBE2v1 complex NSC697923. Western blot analysis confirmed
      that UBE2v1 silencing in HK2 under HG, restored Lys63-beta-actin ubiquitination
      levels to the basal condition. Immunohistochemistry on patients with type 2
      diabetic (T2D) revealed an increase in UBE2v1- and Lys63-ubiquitinated proteins,
      particularly in kidneys of patients with DN compared with control kidneys and
      other nondiabetic renal diseases, such as membranous nephropathy. Increased Lys63
      ubiquitination both in vivo in patients with DN and in vitro, correlated with
      alpha-SMA expression, whereas UBE2v1 silencing reduced HG-induced alpha-SMA
      protein levels, returning them to basal expression. In conclusion, UBE2v1- and
      Lys63-ubiquitinated proteins increase in vitro under HG, as well as in vivo in
      T2D, is augmented in patients with DN, and may affect cytoskeleton organization
      and influence epithelial-to-mesenchymal transition. This process may drive the
      progression of tubular damage and interstitial fibrosis in patients with DN.
      Pontrelli, P., Conserva, F., Papale, M., Oranger, A., Barozzino, M., Vocino, G.,
      Rochetti, M. T., Gigante, M., Castellano, G., Rossini, M., Simone, S., Laviola,
      L., Giorgino, F., Grandaliano, G., Di Paolo, S., Gesualdo, L. Lysine 63
      ubiquitination is involved in the progression of tubular damage in diabetic
      nephropathy.

PMID- 27881487
TI  - Osteogenesis requires FAK-dependent collagen synthesis by fibroblasts and
      osteoblasts.
AB  - Focal adhesion kinase (FAK) is critical in adhesion-dependent signaling, but its
      role in osteogenesis in vivo is ill defined. We deleted Fak in fibroblasts and
      osteoblasts in Floxed-Fak mice bred with those expressing Cre-recombinase driven
      by 3.6-kb alpha1(I)-collagen promoter. Compared with wild-type (WT), conditional
      FAK-knockout (CFKO) mice were shorter (2-fold; P < 0.0001) and had crooked,
      shorter tails (50%; P < 0.0001). Microcomputed tomography analysis showed reduced
      bone volume (4-fold in tails; P < 0.0001; 2-fold in mandibles; P < 0.0001),
      whereas bone surface area/bone volume increased (3-fold in tails; P < 0.0001; 2.5
      fold in mandibles; P < 0.001). Collagen density and fiber alignment in
      periodontal ligament were reduced by 4-fold (P < 0.0001) and 30% (P < 0.05),
      respectively, in CFKO mice. In cultured CFKO osteoblasts, mineralization at d 7
      and mineralizing colony-forming units at d 21 were 30% (P < 0.0001) and >3-fold
      less than WT, respectively. Disruptions of FAK function in osteoblasts by
      conditional knockout, siRNA-knockdown, or FAK inhibitor reduced mRNA and protein
      expression of Runx2 (>30%), Osterix (>25%), and collagen-1 (2-fold). Collagen
      synthesis was abrogated in WT osteoblasts with Runx2 knockdown and in Fak-null
      fibroblasts transfected with an FAK kinase domain mutant or a kinase-impaired
      mutant (Y397F). These data indicate that FAK regulates osteogenesis through
      transcription factors that regulate collagen synthesis.-Rajshankar, D., Wang, Y.,
      McCulloch, C. A. Osteogenesis requires FAK-dependent collagen synthesis by
      fibroblasts and osteoblasts.

PMID- 27881488
TI  - An Opsonic Phagocytosis Assay for Plasmodium falciparum Sporozoites.
AB  - Plasmodium falciparum malaria remains the deadliest parasitic disease worldwide.
      Vaccines targeting the preerythrocytic sporozoite and liver stages have the
      potential to entirely prevent blood-stage infection and disease, as well as
      onward transmission. Sporozoite surface and secreted proteins are leading
      candidates for inclusion in a preerythrocytic stage-specific, antibody-based
      vaccine. Preclinical functional assays to identify humoral correlates of
      protection in vitro and to validate novel sporozoite protein targets for
      inclusion in multisubunit vaccines currently do not consider the interaction of
      sporozoite-targeting antibodies with other components of the immune system. Here,
      we describe the development of a simple flow cytometric assay to quantitatively
      assess the ability of antibodies directed against P. falciparum sporozoites to
      facilitate their phagocytosis. We demonstrate that this sporozoite opsonic
      phagocytosis assay (SOPA) is compatible with both monoclonal antibodies and human
      immune serum and can be performed using cryopreserved P. falciparum sporozoites.
      This simple, accessible assay will aid with the assessment of antibody responses
      to vaccination with Plasmodium antigens and their interaction with phagocytic
      cells of the immune system.

PMID- 27881490
TI  - New Micellar Electrokinetic Chromatographic Method for Analyzing Idebenone in
      Pediatric Formulations.
AB  - A novel, simple and reliable method based on micellar electrokinetic
      chromatography with ultraviolet detection was developed to analyze idebenone in a
      pediatric formulation. Idebenone is a synthetic short chain benzoquinone that
      acts as an electron carrier in the mitochondrial electron transport chain
      facilitating the production of adenosine triphosphate. It can be found in two
      different redox states that differ in their physiological properties. Idebenone
      has been investigated as a treatment in several neurological disorders like
      Friedreich's ataxia, Leber's hereditary optic neuropathy, mitochondrial
      encephalomyopathies and senile dementia. Accordingly, a micellar electrokinetic
      chromatography was employed to discriminate both redox forms. The final optimized
      system was validated in terms of selectivity, linearity (r2 0.992), limit of
      detection (0.5 ug/mL), limit of quantification (1.8 ug/mL), intra- and inter-day
      precision (RSD <= 2) and accuracy in terms of recovery studies (99.3-100.5%).
      Robustness was studied following a Plackett-Burman design. Finally, the validated
      system was applied to the analysis of idebenone in a pediatric formulation.

PMID- 27881489
TI  - Kinetics of Meningococcal Serogroup C-Specific Functional Antibody Levels Up to
      15 Years after a Single Immunization with a Meningococcal Serogroup C Conjugate
      Vaccine during Adolescence.
AB  - Adolescent vaccination is now considered the key factor for offering direct
      protection against meningococcal disease but also for reducing carriage and
      transmission and, in this way, establishing herd protection. This study estimated
      age-dependent patterns in functional meningococcal serogroup C (MenC) antibody
      kinetics after primary MenC conjugate (MenCC) vaccination in adolescents. Serum
      samples (n = 1,676) were drawn from 2006 to 2011 from individuals aged 9 to 18
      years at the time of primary MenCC vaccination in 2002. Functional antibody
      levels were measured with a serum bactericidal antibody assay (SBA) using rabbit
      complement. SBA titers gradually declined with time. Up to 9 years after primary
      vaccination, SBA titers were estimated to be higher in individuals who were aged
      13 to 18 years at priming than in those who were aged 9 to 10 years at priming.
      Based on a linear mixed model, the higher functional antibody levels with age
      seem to be due to the achievement of higher peak levels upon vaccination rather
      than to lower rates of decline. It is estimated that 35 to 50% of individuals who
      received a single primary MenCC vaccination at an age of 9 to 18 years in 2002
      will still have sufficient protective antibody levels 15 years later. Using a
      linear mixed model based on cohort data for a single dated serum sample per
      person, we were able to estimate the level of protection against MenC up to 15
      years after a single vaccination. The current study shows that analysis of
      antibody kinetics can be done using cross-sectional serology data and is
      therefore relevant for future serosurveillance studies.

PMID- 27881492
TI  - Determination of Common Adulterants in Herbal Medicine and Food Samples using
      Core-shell Column Coupled to Tandem Mass Spectrometry.
AB  - High-performance liquid chromatography coupled to tandem mass spectrometry was
      used to develop and validate a rapid method to qualitatively and quantitatively
      analyse 18 common adulterants in herbal medicine and food samples. Initially, the
      mobile phase composition was optimized in three different columns: core-shell,
      monolithic and standard 3.5-um-particle-size columns. The results show that the
      core-shell column provides the best separation. Moreover, the tandem mass
      spectrometry was optimized. The linear range for all adulterants was 0.5-500 MUg
      mL-1. Finally, the samples that were supplied by the Public Authority of Customer
      Protection, Ministry of Health, and those collected from the local market were
      analysed. The results indicate that 7 of 33 analysed samples contained
      adulterants. The adulterated samples mainly contain sildenafil, tadalafil or
      vardenafil. The concentrations of these three adulterants in the samples were
      0.18-39 wt%. This study is the first report in the Sultanate of Oman about
      adulteration in herbal medicine and food samples. The results clearly raise some
      concern and require proper plan of action to increase public awareness about this
      serious issue.

PMID- 27881491
TI  - Quantification of Paclitaxel and Polyaspartate Paclitaxel Conjugate in Beagle
      Plasma: Application to a Pharmacokinetic Study.
AB  - An LC-MS/MS method for the determination of polyaspartate paclitaxel conjugate
      (PASP-PTX) and paclitaxel (PTX) in dog plasma with cephalomannine (Internal
      Standard for PASP-PTX, IS-I) and clopidogrel bisulfate (Internal Standard for
      PTX, IS-II) as the internal standards was developed and validated. Plasma samples
      of PASP-PTX were extracted by ethyl acetate following the hydrolysis reaction,
      while protein precipitation was used for the extraction of PTX using
      acetonitrile. Analytes were separated by a CAPCELL PAK C18 MG II column using a
      gradient elution with the mobile phase (A) 5 mM ammonium containing 0.1% formic
      acid, and (B) acetonitrile. Quantification was performed by monitoring the m/z
      transitions of 286.2/105.0 for PASP-PTX, 264.2/83.0 for IS-I, 854.4/286.0 for
      PTX, and 322.1/184.1 for IS-II in the ESI positive mode. This method was
      validated in terms of specificity, linearity, precision, accuracy, and stability.
      The lower limit of quantification was 0.15 ug/mL for PASP-PTX and 0.01 ug/mL for
      PTX, and the calibration curves were linear over 0.15-300 ug/mL for PASP-PTX and
      over 0.01-10 ug/mL for PTX. The samples were stable under all the tested
      conditions. The method was successfully applied to study the pharmacokinetic
      profiles of PASP-PTX and PTX in beagles following intravenous administration of
      PASP-PTX.

PMID- 27881493
TI  - The Metabolic Profiling of Isorhamnetin-3-O-Neohesperidoside Produced by Human
      Intestinal Flora Employing UPLC-Q-TOF/MS.
AB  - Isorhamnetin-3-O-neohesperidoside is the major active substance of Puhuang, a
      traditional herb medicine widely used in clinical practice to tackle many chronic
      diseases. However, little is known about the interactions between this ingredient
      and intestinal flora. In this study, ultra-performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry together with
      automated data analysis software (MetabolynxTM) was used for analysis of the
      metabolic profile of isorhamnetin-3-O-neohesperidoside by the isolated human
      intestinal bacteria. The parent and three metabolites isorhamnetin-3-O-glucoside,
      isorhamnetin and quercetin were detected and identified based on the
      characteristics of their deprotonated molecules. These metabolites indicated that
      isorhamnetin-3-O-neohesperidoside was firstly deglycosylated to isorhamnetin-3-O
      glucoside and subsequently to the aglycone isorhamnetin, and the latter was
      demethylated to quercetin. The majority of bacteria such as Escherichia sp. 23
      were capable of converting isorhamnetin-3-O-neohesperidoside to considerable
      amounts of aglycone isorhamnetin and further to minor amounts of quercetin, while
      minor amounts of isorhamnetin-3-O-glucoside were detected in minority of
      bacterial samples such as Enterococcus sp. 30. The metabolic pathway and
      metabolites of isorhamnetin-3-O-neohesperidoside by the different human
      intestinal bacteria were firstly investigated. Furthermore, the metabolites of
      isorhamnetin-3-O-neohesperidoside might influence the effects of traditional herb
      medicines. Thus, our study is helpful to further unravel how isorhamnetin-3-O
      neohesperidoside and Puhuang work in vivo.

PMID- 27881494
TI  - A New UPLC Method with Chemometric Design-Optimization Approach for the
      Simultaneous Quantitation of Brimonidine Tartrate and Timolol Maleate in an Eye
      Drop Preparation.
AB  - A new ultra-performance liquid chromatography (UPLC) with photodiode array was
      proposed for the quantitation of Brimonidine Tartrate (BRI) and Timolol Maleate
      (TIM) in eye drop using experimental design and optimization methodology. A 33
      full factorial design was applied to uncover the effects of the selected factors
      and their interactions on the chromatographic response function for the
      optimization of experimental conditions in the development of a new UPLC method.
      As a result, the optimal chromatographic conditions giving a better separation
      and short analysis time were found to be 49.2 degrees C for column temperature;
      0.38 mL/min for flow rate and 56.7 % (v/v) for 0.1 M CH3COOH used in mobile
      phase. The elution of BRI and TIM was reported as 0.508 and 0.652 min within a
      short runtime of 1.5 min, respectively. Calibration graphs for BRI and TIM were
      obtained by the regression of the concentration on the peak area, which was
      detected at 246 and 298 nm, respectively. The method validation was performed by
      the analysis of the synthetic mixtures, intra-day and inter-day samples and
      standard addition samples. This study shows that the optimized and validated UPLC
      method is very promising and available for the quantification of BRI and TIM in
      an eye drop formulation.

PMID- 27881495
TI  - Extraction of Volatile Flavor Compounds From Tobacco Leaf Through a Low-Density
      Polyethylene Membrane.
AB  - A low-density polyethylene (LDPE) membrane pouch method was developed to extract
      volatile flavor compounds from tobacco leaf. Tobacco leaf suspended in water was
      enclosed in a pouch prepared from a LDPE membrane of specific gravity 0.92 g/cm3
      and 0.03 mm thickness and then extracted with diethyl ether. In comparison with
      direct solvent extraction, LDPE membrane excluded larger and higher boiling point
      compounds which could contaminate a gas chromatograph inlet and damage a column.
      Whilst being more convenient than a reduced-pressure steam distillation, it could
      extract volatile flavor compounds of wide range of molecular weight and polarity.
      Repeatabilities in the extracted amounts were ranged from 0.38% of 2.3-bipyridyl
      to 26% of beta-ionone, and average value of 39 compounds was 5.9%.

PMID- 27881496
TI  - Penetrating intracranial injury caused by an unusual home-made iron pyrotechnic
      device.
AB  - Herein, a potentially dangerous explosive home-made device used for fun and
      entertainment is described. It consists of two iron parts connected with a U
      shaped thick wire: a wedge about 8 cm in length, which fits into a hollow
      cylinder, filled with a small amount of nitre (the mineral form of potassium
      nitrate). Striking the device onto a hard surface creates a spark inside it,
      which burns the nitre, producing a very loud bang. We are in possession of such
      device in our forensic museum collection. We present a case from 1937 related to
      the use of this explosive home-made device. A boy was injured using it, as the
      wedge hit him in the left temporal region and entered his skull. The major
      initial consequence was a localised brain injury, without any bleeding. Delayed
      presentation resulted in intracranial infection - purulent meningitis due to open
      craniocerebral injury, which was the cause of death three months later. The
      potentially dangerous home-made explosive iron device presented here was in use
      mostly by children from the end of the 19th century until the early 1970s, when
      it was replaced with less dangerous and cheaper Chinese firecrackers and
      fireworks.

PMID- 27881497
TI  - Discovering and Developing Successful Cardiovascular Therapeutics: A Conversation
      With James N. Topper, MD, PhD.
AB  - Dr James (also known as Jamie) N. Topper, MD, PhD, serves as Managing General
      Partner at Frazier Healthcare Partners, where he leads the Life Science Venture
      practice. In 2011, and 2016, he was named to the Midas List of leading venture
      capitalists, and, in 2013, he was recognized by Forbes as one of the top 10
      healthcare investors. He has >25 years of experience working with entrepreneurs
      to found and build successful therapeutics-focused companies. Dr Topper holds a
      BS from the University of Michigan. He received an MD and PhD (in biophysics)
      from Stanford University School of Medicine. He completed postgraduate training
      in internal medicine and cardiovascular disease at the Brigham and Women's
      Hospital in Boston and is board certified in both disciplines.

PMID- 27881498
TI  - Association Between Emergency Department Closure and Treatment, Access, and
      Health Outcomes Among Patients With Acute Myocardial Infarction.

PMID- 27881499
TI  - Letter by Kothari Regarding Article, "Tropical Endomyocardial Fibrosis: Natural
      History, Challenges, and Perspectives".

PMID- 27881500
TI  - Response by Grimaldi et al to Letter Regarding Article, "Tropical Endomyocardial
      Fibrosis: Natural History, Challenges, and Perspectives".

PMID- 27881501
TI  - Letter by Gallucci and Storto Regarding Article, "Vascular Toxicities of Cancer
      Therapies: The Old and the New-An Evolving Avenue".

PMID- 27881502
TI  - Response by Herrmann et al to Letter Regarding Article, "Vascular Toxicities of
      Cancer Therapies: The Old and the New-An Evolving Avenue".

PMID- 27881503
TI  - The Preventive-Pill Paradox: How Shared Decision Making Could Increase
      Cardiovascular Morbidity and Mortality.

PMID- 27881504
TI  - Now That I Am a Hospital Executive.

PMID- 27881505
TI  - Prasugrel Versus Ticagrelor: Uncertainty Remains.

PMID- 27881506
TI  - Development and Evolution of a Hierarchical Clinical Composite End Point for the
      Evaluation of Drugs and Devices for Acute and Chronic Heart Failure: A 20-Year
      Perspective.
AB  - Traditional approaches to the assessment of new treatments for heart failure have
      generally evaluated individual components of the syndrome at fixed points in time
      or have relied on surrogate physiological measures that are poorly correlated
      with the clinical status of patients. Conventional time-to-event trials that
      focus on morbidity and mortality represent an important methodological advance,
      but they generally assign undue weight to clinical events of less importance and
      are insensitive to difference in functional capacity among individuals who do not
      experience a clinical event during follow-up. Twenty years ago, a hierarchical
      clinical composite was developed to address these limitations; it aims to assess
      the clinical course of patients as a physician would in practice by combining a
      symptomatic assessment of the patient at each visit with an evaluation of the
      clinical stability of the patient between visits. The composite does not generate
      a numeric score by summing arbitrarily assigned weights to certain symptoms or
      events; instead, the composite ranks relevant measures and outcomes according to
      clinical priority. In doing so, the clinical composite minimizes the biases
      created by noncompleting patients in the assessment of symptoms or exercise
      tolerance while expanding the range of patients who contribute to the treatment
      difference in a typical morbidity and mortality trial. When applied
      appropriately, the hierarchical clinical composite end point has reliably
      distinguished effective from ineffective treatments. The composite may have
      particular advantages in the evaluation of new devices and transcatheter
      interventions in chronic heart failure and of new drugs for acute heart failure.
      Recent modifications enhance its discriminant characteristics and its ability to
      accurately assess the efficacy of novel interventions for heart failure.

PMID- 27881507
TI  - Highlights of the 27th Great Wall International Congress of Cardiology.

PMID- 27881509
TI  - Ongoing Research Points to Key Role of Gut Microbes in Cardiovascular Health.

PMID- 27881510
TI  - Congenital Heart Defects and Risk of Epilepsy: A Population-Based Cohort Study.

PMID- 27881511
TI  - Sex-Discordant Blood Transfusions and Survival After Cardiac Surgery: A
      Nationwide Cohort Study.

PMID- 27881512
TI  - Letter by Sueta et al Regarding Article, "Urgent Need to Measure Effects of
      Direct Oral Anticoagulants".

PMID- 27881513
TI  - Response by Weitz and Eikelboom to Letter Regarding Article, "Urgent Need to
      Measure Effects of Direct Oral Anticoagulants".

PMID- 27881514
TI  - Letter by Dixon et al Regarding Article, "Watching Television and Risk of
      Mortality From Pulmonary Embolism Among Japanese Men and Women: The JACC Study
      (Japan Collaborative Cohort)".

PMID- 27881515
TI  - Response by Shirakawa and Iso to Letter Regarding Article, "Watching Television
      and Risk of Mortality From Pulmonary Embolism Among Japanese Men and Women: The
      JACC Study (Japan Collaborative Cohort)".

PMID- 27881516
TI  - Letter by Mascitelli and Goldstein Regarding Article, "Is Statin Monotherapy the
      Perfect Polypill?"

PMID- 27881517
TI  - Overview of phase IV clinical trials for postmarket drug safety surveillance: a
      status report from the ClinicalTrials.gov registry.
AB  - OBJECTIVE: Phase IV trials are often used to investigate drug safety after
      approval. However, little is known about the characteristics of contemporary
      phase IV clinical trials and whether these studies are of sufficient quality to
      advance medical knowledge in pharmacovigilance. We aimed to determine the
      fundamental characteristics of phase IV clinical trials that evaluated drug
      safety using the ClinicalTrials.gov registry data. METHODS: A data set of 19 359
      phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The
      characteristics of the phase IV trials focusing on safety only were compared with
      those evaluating both safety and efficacy. We also compared the characteristics
      of the phase IV trials in three major therapeutic areas (cardiovascular diseases,
      mental health and oncology). Multivariable logistic regression was used to
      evaluate factors associated with the use of blinding and randomisation. RESULTS:
      A total of 4772 phase IV trials were identified, including 330 focusing on drug
      safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV
      trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among
      these trials, 8.2% were terminated or withdrawn. Factors associated with the use
      of blinding and randomisation included the intervention model, clinical specialty
      and lead sponsor. CONCLUSIONS: Phase IV trials evaluating drug safety in the
      ClinicalTrials.gov registry were dominated by small trials that might not have
      sufficient power to detect less common adverse events. An adequate sample size
      should be emphasised for phase IV trials with safety surveillance as main task.

PMID- 27881519
TI  - Comparison of therapy persistence for fixed versus free combination
      antihypertensives: a retrospective cohort study.
AB  - OBJECTIVES: The aim of the study was to compare therapy persistence among
      patients who started with one of three drug regimens: a monotherapy, or
      combination therapy either as a fixed combination (ie, 'single pill') or as a
      free combination (ie, two separate antihypertensive agents). DESIGN: In a
      secondary data analysis, we used descriptive statistics and multivariate logistic
      regression to measure the effect of the three therapy regimens on therapy
      persistence over 4 years. SETTING: Prescription data from a large German
      statutory health insurance provider. PARTICIPANTS: All patients who started with
      a new antihypertensive therapy in 2007 or 2008 (n=8032) were included and
      followed for 4 years. PRIMARY OUTCOME MEASURE: Therapy persistence, defined as
      receiving a refill prescription no later than within 180 days. RESULTS: The
      persistence rates after 4 years were nearly identical among patients who started
      with a monotherapy (40.3%) or a fixed combination of two drugs (39.8%). However,
      significantly more patients who started with free-drug combinations remained
      therapy persistent (56.4%), resulting in an OR of 2.00 (95% CI 1.6 to 2.5;
      p<0.0001) for free combinations versus fixed combinations. This trend was
      observed in all age groups and for men and women. At the end of the study period,
      the number of different antihypertensive agents was still similar between
      patients who started with a fixed combination (2.41) and patients who started
      with a free combination (2.28). CONCLUSIONS: While single-pill combinations make
      it easier to take different drugs at once, the risk is high that these several
      substances are stopped at once. Therapy persistence was significantly better for
      patients who started with a free-drug combination without taking much fewer
      different antihypertensive drugs as those with a fixed combination.

PMID- 27881520
TI  - Is Olympic inspiration associated with fitness and physical activity in English
      schoolchildren? A repeated cross-sectional comparison before and 18 months after
      London 2012.
AB  - OBJECTIVES: To compare cardiovascular fitness and physical activity of
      schoolchildren 18 months after London 2012 according to Olympic 'inspiration'.
      DESIGN: A cross-sectional comparison between groups of schoolchildren categorised
      according to self-reported Olympic inspiration and a repeated cross-sectional
      comparison using data collected pre-2012. SETTING: Schools within a 50 km radius
      of the Olympic Park, Stratford, London. PARTICIPANTS: 931 students (10.0-15.9
      year-olds) attending 6 schools assessed in 2013 and 2014 (18 (range: 14-20)
      months after London 2012) and 733 students from the same schools assessed in 2008
      2009 (42 (range: 38-46) months before London 2012). PRIMARY OUTCOME MEASURES:
      Self-reported Olympic inspiration; cardiorespiratory fitness ([Formula: see text]
      mL/kg/min) assessed using the 20 m shuttle-run and self-reported physical
      activity. SECONDARY OUTCOMES MEASURES: Differences in [Formula: see text] before
      and after London 2012. RESULTS: 53% of children reported being inspired to try
      new sports or activities. Compared with those not inspired by the Games,
      [Formula: see text] was higher in boys (d=0.43) and girls (d=0.27), who continued
      to participate in activities at 18(14-20) months. This 45% of sample was also
      more physically active (boys, d=0.23; girls, d=0.38) than those not or only
      briefly inspired to participate in activities (boys, d=0.24; girls, d=0.21).
      Compared with pre-2012 values, [Formula: see text] was lower post-2012 in boys
      (d=0.37) and in girls (d=0.38). CONCLUSIONS: High levels of inspiration to
      participate in new activities reported following London 2012 and positive
      associations with fitness are encouraging. We cannot discount the possibility
      that inspired participants may have already been fitter and more active pre-2012.
      These associations must be interpreted in the context of the significant declines
      in fitness shown by our repeated cross-sectional comparison. Olympic host
      countries should employ longitudinal monitoring using objectively measured
      fitness and physical activity to provide evidence of health-related legacy.

PMID- 27881521
TI  - Is famine exposure during developmental life in rural Bangladesh associated with
      a metabolic and epigenetic signature in young adulthood? A historical cohort
      study.
AB  - OBJECTIVES: Famine exposure in utero can 'programme' an individual towards type 2
      diabetes and obesity in later life. We sought to identify, (1) whether
      Bangladeshis exposed to famine during developmental life are programmed towards
      diabetes and obesity, (2) whether this programming was specific to gestational or
      postnatal exposure windows and (3) whether epigenetic differences were associated
      with famine exposure. DESIGN: A historical cohort study was performed as part of
      a wider cross-sectional survey. Exposure to famine was defined through birth date
      and historical records and participants were selected according to: (A) exposure
      to famine in postnatal life, (B) exposure to famine during gestation and (C)
      unexposed. SETTING: Matlab, a rural area in the Chittagong division of
      Bangladesh. PARTICIPANTS: Young adult men and women (n=190) recruited to a
      historical cohort study with a randomised subsample included in an epigenetic
      study (n=143). OUTCOME MEASURES: Primary outcome measures of weight, body mass
      index and oral glucose tolerance tests (0 and 120 min glucose). Secondary outcome
      measures included DNA methylation using genome-wide and targeted analysis of
      metastable epialleles sensitive to maternal nutrition. RESULTS: More young adults
      exposed to famine in gestation were underweight than those postnatally exposed or
      unexposed. In contrast, more young adults exposed to famine postnatally were
      overweight compared to those gestationally exposed or unexposed. Underweight
      adults exposed to famine in gestation in utero were hyperglycaemic following a
      glucose tolerance test, and those exposed postnatally had elevated fasting
      glucose, compared to those unexposed. Significant differences in DNA methylation
      at seven metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA,
      EXD3) known to vary with gestational famine exposure were identified.
      CONCLUSIONS: Famine exposure in developmental life programmed Bangladeshi
      offspring towards diabetes and obesity in adulthood but gestational and postnatal
      windows of exposure had variable effects on phenotype. DNA methylation
      differences were replicated at previously identified metastable epialleles
      sensitive to periconceptual famine exposure.

PMID- 27881518
TI  - Study protocol for a randomised controlled trial of brief, habit-based, lifestyle
      advice for cancer survivors: exploring behavioural outcomes for the Advancing
      Survivorship Cancer Outcomes Trial (ASCOT).
AB  - INTRODUCTION: Positive health behaviours such as regular physical activity and a
      healthy diet have significant effects on cancer outcomes. There is a need for
      simple but effective behaviour change interventions with the potential to be
      implemented within the cancer care pathway. Habit-based advice encourages
      repetition of a behaviour in a consistent context so that the behaviour becomes
      increasingly automatic in response to a specific contextual cue. This approach
      therefore encourages long-term behaviour change and can be delivered through
      printed materials. 'Healthy Habits for Life' is a brief intervention based on
      habit theory, and incorporating printed materials plus a personally tailored
      discussion, that has been designed specifically for patients with a diagnosis of
      cancer. The aim of this trial was to test the effect of 'Healthy Habits for Life'
      on a composite health behaviour risk index (CHBRI) over 3 months in patients with
      a diagnosis of breast, colorectal or prostate cancer. METHOD AND ANALYSIS: A 2
      arm, individually randomised controlled trial in patients with breast, colorectal
      and prostate cancer. Patients will be recruited over 18 months from 7 National
      Health Service Trusts in London and Essex. Following baseline assessments and
      allocation to intervention or usual care, patients are followed up at 3 and 6
      months. The primary outcome will be change in CHBRI at 3 months. Maintenance of
      any changes over 6 months, and changes in individual health behaviours (including
      dietary intake, physical activity, alcohol consumption and smoking status) will
      also be explored. ETHICS AND DISSEMINATION: Ethical approval was obtained through
      the National Research Ethics Service Committee South Central-Oxford B via the
      Integrated Research Application System (reference number 14/SC/1369). Results of
      this study will be disseminated through peer-reviewed publications and scientific
      presentations. TRIAL REGISTRATION NUMBER: 17421871.

PMID- 27881522
TI  - Prevalence of papillomavirus in Brazil: a systematic review protocol.
AB  - INTRODUCTION: Human papillomavirus (HPV) infection is a cause of premalignant and
      malignant cancer in the lower genital and digestive tracts. In Brazil, there have
      been no prevalence studies that included a nationwide sample, and the prevalence
      of HPV has not been determined in many regions. METHODS: We will search the
      EMBASE, LILACS, MEDLINE, Web of Science and SciELO databases and previously
      published review articles to identify original research articles assessing HPV
      prevalence of the perineal (cervical, penile and anal) and oral areas. No
      exclusion criteria related to language or publication date will apply. 2
      reviewers will independently screen for eligibility and perform data extraction.
      Discrepancies will be resolved through consensus; the opinion of a third reviewer
      will be sought as necessary. Relevant measures and data about study and
      population characteristics will be extracted from the included studies. Where
      possible, study prevalence will be pooled using a random-effects meta-analysis.
      The methodological quality of the studies will be assessed using an adapted
      version of the NIH 'Quality Assessment Tool for Observational Cohort and Cross
      Sectional Studies'. The overall quality of evidence will be assessed using
      Grading of Recommendations Assessment, Development and Evaluation (GRADE). ETHICS
      AND DISSEMINATION: We expect to estimate the prevalence of perineal and oral HPV
      infection in the general population as well as the prevalence of HPV infection in
      individuals with premalignant and malignant lesions in Brazil and its 5
      geographic regions. This systematic review does not require ethical approval.
      TRIAL REGISTRATION NUMBER: CRD42016032751.

PMID- 27881524
TI  - Why articles are retracted: a retrospective cross-sectional study of retraction
      notices at BioMed Central.
AB  - OBJECTIVES: To assess why articles are retracted from BioMed Central journals,
      whether retraction notices adhered to the Committee on Publication Ethics (COPE)
      guidelines, and are becoming more frequent as a proportion of published articles.
      DESIGN/SETTING: Retrospective cross-sectional analysis of 134 retractions from
      January 2000 to December 2015. RESULTS: 134 retraction notices were published
      during this timeframe. Although they account for 0.07% of all articles published
      (190 514 excluding supplements, corrections, retractions and commissioned
      content), the rate of retraction is rising. COPE guidelines on retraction were
      adhered to in that an explicit reason for each retraction was given. However,
      some notices did not document who retracted the article (eight articles, 6%) and
      others were unclear whether the underlying cause was honest error or misconduct
      (15 articles, 11%). The largest proportion of notices was issued by the authors
      (47 articles, 35%). The majority of retractions were due to some form of
      misconduct (102 articles, 76%), that is, compromised peer review (44 articles,
      33%), plagiarism (22 articles, 16%) and data falsification/fabrication (10
      articles, 7%). Honest error accounted for 17 retractions (13%) of which 10
      articles (7%) were published in error. The median number of days from publication
      to retraction was 337.5 days. CONCLUSIONS: The most common reason to retract was
      compromised peer review. However, the majority of these cases date to March 2015
      and appear to be the result of a systematic attempt to manipulate peer review
      across several publishers. Retractions due to plagiarism account for the second
      largest category and may be reduced by screening manuscripts before publication
      although this is not guaranteed. Retractions due to problems with the data may be
      reduced by appropriate data sharing and deposition before publication. Adopting a
      checklist (linked to COPE guidelines) and templates for various classes of
      retraction notices would increase transparency of retraction notices in future.

PMID- 27881523
TI  - Effects of culture-sensitive adaptation of patient information material on
      usefulness in migrants: a multicentre, blinded randomised controlled trial.
AB  - OBJECTIVES: To evaluate the usefulness of culture-sensitive patient information
      material compared with standard translated material. DESIGN: Multicentre, double
      blind randomised controlled trial. SETTING: 37 primary care practices.
      PARTICIPANTS: 435 adult primary care patients with a migration background with
      unipolar depressive disorder or non-specific chronic low back pain were
      randomised. Patients who were unable to read in the language of their respective
      migration background were excluded. Sufficient data were obtained from 203 women
      and 106 men. The largest group was of Russian origin (202 patients), followed by
      those of Turkish (52), Polish (30) and Italian (25) origin. INTERVENTIONS:
      Intervention group: provision of culture-sensitive adapted material. CONTROL
      GROUP: provision of standard translated material. MAIN OUTCOME MEASURES: Primary
      outcome: patient-rated usefulness (USE) assessed immediately after patients
      received the material. SECONDARY OUTCOMES: patient-rated usefulness after 8 weeks
      and 6 months, symptoms of depression (PHQ-9), back pain (Back Pain Core Set) and
      quality of life (WHO-5) assessed at all time points. RESULTS: Usefulness was
      found to be significantly higher (t=1.708, one-sided p=0.04) in the intervention
      group (USE-score=65.08, SE=1.43), compared with the control group (61.43,
      SE=1.63), immediately after patients received the material, in the intention-to
      treat analysis, with a mean difference of 3.65 (one-sided 95% lower confidence
      limit=0.13). No significant differences were found for usefulness at follow-up
      (p=0.16, p=0.71). No significant effect was found for symptom severity in
      depression (p=0.95, p=0.66, p=0.58), back pain (p=0.40, p=0.45, p=0.32) or
      quality of life (p=0.76, p=0.86, p=0.21), either immediately after receiving the
      material, or at follow-up (8 weeks; 6 months). Patients with a lower level of
      dominant society immersion benefited substantially and significantly more from
      the intervention than patients with a high level of immersion (p=0.005).
      CONCLUSION: Cultural adaptation of patient information material provides benefits
      over high quality translations. Clinicians are encouraged to use culture
      sensitive material in their consultations, particularly with low-acculturated
      patients. TRIAL REGISTRATION NUMBER: German Register for Clinical Trials:
      DRKS00004241, Universal Trial Number: U1111-1135-8043, Results.

PMID- 27881525
TI  - Rationale and protocol for using a smartphone application to study autism
      spectrum disorders: SMARTAUTISM.
AB  - INTRODUCTION: Longitudinal studies on the evolution of autism spectrum disorder
      (ASD) symptoms are limited and have primarily used repeated measurements
      performed several months apart. However, measurements of changes in everyday life
      should more closely reflect the 'real life' of the patient and his or her family.
      We propose to study the child's ASD symptoms and their effect on the quality of
      life, psychological status and anxiety of the child's parents over a 6-month
      period using SMARTAUTISM, a smartphone application. METHOD AND ANALYSIS: This is
      a prospective, longitudinal, exploratory, open study with a 6-month follow-up
      period. Data will be recorded longitudinally over multiple weeks under natural
      conditions. The factors affecting the quality of life and anxiety of parents of
      children with ASD and the children's functional symptoms will be examined, and
      the feasibility of using a smartphone application designed for parents of ASD
      patients will be assessed. PRIMARY OBJECTIVE: Explore the evolution of a child's
      behaviour over 6 months and the (psychological and social) effects of these
      changes on the family. SECONDARY OBJECTIVE: Assess the feasibility of our
      application by examining the filling rate and application usage by parents for 6
      months. 100 families containing 1 child diagnosed with ASD will be included. At
      baseline, sociodemographic, psychiatric and medical data will be recorded. The
      correlations of the general epidemiological variables (primary outcome measure)
      will be evaluated via multivariate analysis. The application filling rate
      (relative to the ideal filling rate) will be used to assess the feasibility of
      the application (secondary outcome measure). ETHICS AND DISSEMINATION: The
      SMARTAUTISM study has the approval of the local ethics committee, and data
      security will be ensured via the use of encryption and a secure medical server.
      The use of this application will be proposed at autism resource centres across
      France.

PMID- 27881526
TI  - Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium: a
      study protocol.
AB  - INTRODUCTION: Cerebral venous thrombosis (CVT) is a rare cerebrovascular
      condition accounting for <1% of all stroke cases and mainly affects young adults.
      Its genetic aetiology is not clearly elucidated. METHODS AND ANALYSIS: To better
      understand the genetic basis of CVT, we have established an international biobank
      of CVT cases, Biorepository to Establish the Aetiology of Sinovenous Thrombosis
      (BEAST) which aims to recruit highly phenotyped cases initially of European
      descent and later from other populations. To date we have recruited 745 CVT cases
      from 12 research centres. As an initial step, the consortium plans to undertake a
      genome-wide association analysis of CVT using the Illumina Infinium
      HumanCoreExome BeadChip to assess the association and impact of common and low
      frequency genetic variants on CVT risk by using a case-control study design.
      Replication will be performed to confirm putative findings. Furthermore, we aim
      to identify interactions of genetic variants with several environmental and
      comorbidity factors which will likely contribute to improve the understanding of
      the biological mechanisms underlying this complex disease. ETHICS AND
      DISSEMINATION: BEAST meets all ethical standards set by local institutional
      review boards for each of the participating sites. The research outcomes will be
      published in international peer-reviewed open-access journals with high impact
      and visibility. The results will be presented at national and international
      meetings to highlight the contributions into improving the understanding of the
      mechanisms underlying this uncommon but important disease. This international DNA
      repository will become an important resource for investigators in the field of
      haematological and vascular disorders.

PMID- 27881527
TI  - Clinical factors associated with initiation of and persistence with ADP receptor
      inhibiting oral antiplatelet treatment after acute coronary syndrome: a
      nationwide cohort study from Finland.
AB  - OBJECTIVES: To study patient selection for and persistence with ADP receptor
      inhibiting oral antiplatelet (OAP) treatment after acute coronary syndrome (ACS).
      DESIGN: Observational, retrospective, cohort study linking real-life patient
      level register data. SETTING: Nationwide drug usage study using data of patients
      with ACS discharged from hospitals in Finland. PARTICIPANTS: The study population
      consisted of 54 416 patients (aged >=18 years) following hospital admission for
      unstable angina pectoris or myocardial infarction during 2009-2013. Patients were
      classified as either OAP or non-OAP users based on drug purchases within 7 days
      of discharge. OUTCOME MEASURES: Initiation of and a 12-month persistence with OAP
      medication. RESULTS: In total, 49% of patients with ACS received OAP treatment
      after hospital discharge. Women represented 40% of the population, but only 32%
      of them became OAP users (adjusted OR for initiation compared with men 0.8;
      p<0.001). Patients not treated with percutaneous coronary intervention (PCI),
      elderly and patients with dementia/Alzheimer's disease, atrial fibrillation or
      warfarin treatment were less likely to be treated with OAP. If initiated, they
      were less likely to complete the recommended 12 months' medication (adjusted risk
      increment >38% and p<0.001 for all). The OAP users showed good compliance with
      immediate initiation (92% within 1 day of discharge) and high mean medication
      possession rate (99%). Among OAP users, the usage of other secondary prevention
      drugs after ACS was more common than in non-OAP-treated patients (difference >20
      percentage points for each). CONCLUSIONS: Only half of the patients with ACS
      received guideline-recommended ADP receptor-inhibiting OAP treatment after
      hospital discharge, suggesting suboptimal treatment practices. Non-PCI-treated
      patients and patients with increased age, unstable angina, dementia or atrial
      fibrillation appear to have the highest risk of deficient treatment with OAPs.
      OAP users, however, showed good compliance during drug usage.

PMID- 27881528
TI  - Life-course socioeconomic status and breast and cervical cancer screening:
      analysis of the WHO's Study on Global Ageing and Adult Health (SAGE).
AB  - OBJECTIVES: Socioeconomic differences in screening have been well documented in
      upper-income countries; however, few studies have examined socioeconomic status
      (SES) over the life-course in relation to cancer screening in lower-income and
      middle-income countries. Here, we examine individual, parental and life-course
      SES differences in breast and cervical cancer screening among women in India,
      China, Mexico, Russia and South Africa. SETTING: Data from the WHO's Study on
      Global Ageing and Adult Health (SAGE) 2007-2008 data were used for survey
      weighted multivariable regression analysis. We examined the association between
      individual, parental and life-course SES in relation to breast and cervical
      cancer screening using education-based and employment-based measures of SES.
      PARTICIPANTS: 22 283 women aged 18-65 years, recruited from China, India, Mexico,
      Russia and South Africa. RESULTS: Having a college degree (OR 4.18; 95% CI 2.36
      to 7.40) increased the odds of breast cancer screening compared with no formal
      education. Women with higher parental SES were almost 10 times more likely to
      receive breast cancer screening (OR 9.84; 95% CI 1.75 to 55.5) compared with
      women with low parental SES. Stable higher life-course (OR 3.07; 95% CI 1.96 to
      4.79) increased breast cancer screening by threefold and increased cervical
      cancer screening by more than fourfold (OR 4.35; 95% CI 2.94 to 6.45); however,
      declining life-course SES was associated with reduced breast cancer screening (OR
      0.26; 95% CI 0.08 to 0.79) compared to low life-course SES. CONCLUSIONS: Higher
      individual, parental and life-course SES was positively associated with breast
      and cervical cancer screening, although education-based SES measures were
      stronger predictors of screening compared with employment-based measures.
      Improving knowledge of the benefits of cancer screening and integrating cancer
      screening into routine healthcare practice for low SES women are actionable
      strategies that may significantly improve screening rates in low-income and
      middle-income countries.

PMID- 27881529
TI  - Co-occurrence and clustering of health conditions at age 11: cross-sectional
      findings from the Millennium Cohort Study.
AB  - OBJECTIVES: To identify patterns of co-occurrence and clustering of 6 common
      adverse health conditions in 11-year-old children and explore differences by
      sociodemographic factors. DESIGN: Nationally representative prospective cohort
      study. SETTING: Children born in the UK between 2000 and 2002. PARTICIPANTS: 11
      399 11-year-old singleton children for whom data on all 6 health conditions and
      sociodemographic information were available (complete cases). MAIN OUTCOME
      MEASURES: Prevalence, co-occurrence and clustering of 6 common health conditions:
      wheeze; eczema; long-standing illness (excluding wheeze and eczema); injury;
      socioemotional difficulties (measured using Strengths and Difficulties
      Questionnaire) and unfavourable weight (thin/overweight/obese vs normal).
      RESULTS: 42.4% of children had 2 or more adverse health conditions (co
      occurrence). Co-occurrence was more common in boys and children from lower income
      households. Latent class analysis identified 6 classes: 'normative' (57.4%):
      'atopic burdened' (14.0%); 'socioemotional burdened' (11.0%); 'unfavourable
      weight/injury' (7.7%); 'eczema/injury' (6.0%) and 'eczema/unfavourable weight'
      (3.9%). As with co-occurrence, class membership differed by sociodemographic
      factors: boys, children of mothers with lower educational attainment and children
      from lower income households were more likely to be in the 'socioemotional
      burdened' class. Children of mothers with higher educational attainment were more
      likely to be in the 'normative' and 'eczema/unfavourable weight' classes.
      CONCLUSIONS: Co-occurrence of adverse health conditions at age 11 is common and
      is associated with adverse socioeconomic circumstances. Holistic, child focused
      care, particularly in boys and those in lower income groups, may help to prevent
      and reduce co-occurrence in later childhood and adolescence.

PMID- 27881531
TI  - Burnout prevalence in New Zealand's public hospital senior medical workforce: a
      cross-sectional mixed methods study.
AB  - OBJECTIVES: To explore the prevalence of, and associated factors contributing to
      burnout among senior doctors and dentists working in the New Zealand's public
      health system. DESIGN: Cross-sectional, mixed methods study. SETTING: New
      Zealand's 20 district health boards (DHBs). PARTICIPANTS: A total of 1487 of 3740
      senior doctors and dentists who are members of the Association of Salaried
      Medical Specialists working in DHBs were recruited (response rate 40%). PRIMARY
      AND SECONDARY OUTCOME MEASURES: Gender, age, self-rated health status, vocation
      and hours of work per week were obtained from an electronic questionnaire.
      Burnout was measured using the Copenhagen Burnout Inventory. Qualitative data
      taken from an open-ended comments section was coded using grounded theory and
      used for contextual data. RESULTS: The overall prevalence of high personal
      burnout was 50%. Women aged <40 years had 71% prevalence of high personal
      burnout. Prevalence of high work-related burnout and patient-related burnout was
      42% and 16%, respectively. Those working in emergency medicine and psychiatry had
      significantly higher mean work-related burnout than other specialties (p<0.001).
      On multivariate analysis, having fair or poor health status (OR 10.8, 95% CI 6.8
      to 17.1), working more than 14 consecutive hours (OR 1.43, 95% CI 1.12 to 1.82)
      and being a woman (OR 2.14, 95% CI 1.68 to 2.73) were independently associated
      with high personal and work-related burnout. Personal burnout rates decreased
      with age (age 30-39 OR 2.86, 95% CI 1.78 to 4.59, age 40-49 OR 2.45, 95% CI 1.70
      to 3.55, age 50-59 OR 1.70, 95% CI 1.17 to 2.46, compared with age>60).
      Qualitative data emphasised intense and unrelenting workloads, under-staffing,
      onerous on-call duties and frustrations with management as factors contributing
      to burnout. CONCLUSIONS: High burnout appears prevalent in New Zealand's senior
      doctors and dentists. Many attribute their feelings of burnout to work
      conditions. These findings may assist with understanding contributors to burnout
      and with developing strategies to ameliorate the high burnout found across this
      cohort.

PMID- 27881533
TI  - Seven Bacteriophages Isolated from the Female Urinary Microbiota.
AB  - Recent research has debunked the myth that urine is sterile, having uncovered
      bacteria within the bladders of healthy individuals. However, the identity,
      diversity, and putative roles of bacteriophages in the bladder are unknown. We
      report the draft genome sequences of seven bacteriophages isolated from microbial
      communities from adult female bladders.

PMID- 27881530
TI  - Menstrual cups and sanitary pads to reduce school attrition, and sexually
      transmitted and reproductive tract infections: a cluster randomised controlled
      feasibility study in rural Western Kenya.
AB  - OBJECTIVES: Conduct a feasibility study on the effect of menstrual hygiene on
      schoolgirls' school and health (reproductive/sexual) outcomes. DESIGN: 3-arm
      single-site open cluster randomised controlled pilot study. SETTING: 30 primary
      schools in rural western Kenya, within a Health and Demographic Surveillance
      System. PARTICIPANTS: Primary schoolgirls 14-16 years, experienced 3 menses, no
      precluding disability, and resident in the study area. INTERVENTIONS: 1
      insertable menstrual cup, or monthly sanitary pads, against 'usual practice'
      control. All participants received puberty education preintervention, and hand
      wash soap during intervention. Schools received hand wash soap. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Primary: school attrition (drop-out, absence);
      secondary: sexually transmitted infection (STI) (Trichomonas vaginalis, Chlamydia
      trachomatis, Neisseria gonorrhoea), reproductive tract infection (RTI) (bacterial
      vaginosis, Candida albicans); safety: toxic shock syndrome, vaginal
      Staphylococcus aureus. RESULTS: Of 751 girls enrolled 644 were followed-up for a
      median of 10.9 months. Cups or pads did not reduce school dropout risk
      (control=8.0%, cups=11.2%, pads=10.2%). Self-reported absence was rarely reported
      and not assessable. Prevalence of STIs in the end-of-study survey among controls
      was 7.7% versus 4.2% in the cups arm (adjusted prevalence ratio (aPR) 0.48, 0.24
      to 0.96, p=0.039), 4.5% with pads (aPR=0.62; 0.37 to 1.03, p=0.063), and 4.3%
      with cups and pads pooled (aPR=0.54, 0.34 to 0.87, p=0.012). RTI prevalence was
      21.5%, 28.5% and 26.9% among cup, pad and control arms, 71% of which were
      bacterial vaginosis, with a prevalence of 14.6%, 19.8% and 20.5%, per arm,
      respectively. Bacterial vaginosis was less prevalent in the cups (12.9%) compared
      with pads (20.3%, aPR=0.65, 0.44 to 0.97, p=0.034) and control (19.2%, aPR=0.67,
      0.43 to 1.04, p=0.075) arm girls enrolled for 9 months or longer. No adverse
      events were identified. CONCLUSIONS: Provision of menstrual cups and sanitary
      pads for ~1 school-year was associated with a lower STI risk, and cups with a
      lower bacterial vaginosis risk, but there was no association with school dropout.
      A large-scale trial on menstrual cups is warranted. TRIAL REGISTRATION:
      ISRCTN17486946; Results.

PMID- 27881532
TI  - Genome Sequence of Mycobacteriophage ErnieJ.
AB  - ErnieJ, a cluster C mycobacteriophage that infects Mycobacterium smegmatis
      mc2155, was recovered from soil in Washington, DC. Its genome is 153,243 bp in
      size and encodes 227 predicted proteins, 30 tRNAs, and one transfer-messenger RNA
      (tmRNA). Ten percent of the predicted proteins have homologs in phages that
      infect nonmycobacterial Actinobacteria.

PMID- 27881535
TI  - Draft Genome Sequence of the Fungus Penicillium solitum NJ1.
AB  - Penicillium solitum is one of the most prevalent species causing postharvest
      decay of pomaceous fruits during storage. Here, we report the draft genome of P.
      solitum strain NJ1, received as a transfer of a strain originally identified as
      P. griseofulvum by classical means.

PMID- 27881534
TI  - Genome Sequencing and Analysis of the Filamentous Fungus Penicillium sclerotiorum
      113, Isolated after Hurricane Sandy.
AB  - Penicillium sclerotiorum is a distinctive species within the genus Penicillium
      that usually produces vivid orange to red colonies, sometimes with colorful
      sclerotia. Here, we report the first draft genome sequence of P. sclerotiorum
      strain 113, isolated in 2013 in the aftermath of Hurricane Sandy from a flooded
      home in New Jersey.

PMID- 27881536
TI  - Complete Genome Sequence of Edwardsiella piscicida Isolate S11-285 Recovered from
      Channel Catfish (Ictalurus punctatus) in Mississippi, USA.
AB  - Edwardsiella piscicida is a recently described Gram-negative facultative anaerobe
      and an important pathogen to many wild and cultured fish species worldwide. Here,
      we report the complete and annotated genome of E. piscicida isolate S11-285
      recovered from channel catfish (Ictalurus punctatus), consisting of a chromosome
      of 3,923,603 bp and 1 plasmid.

PMID- 27881537
TI  - Complete Genome Sequence of Mycobacterium chimaera Strain AH16.
AB  - Mycobacterium chimaera is a nontuberculous mycobacterial species that causes
      cardiovascular, pulmonary, and postsurgical infections. Here, we report the first
      complete genome sequence of M. chimaera This genome is 6.33 Mbp, with a G+C
      content of 67.56%, and encodes 4,926 protein-coding genes, as well as 74 tRNAs,
      one ncRNA, and three rRNA genes.

PMID- 27881538
TI  - Near-Complete Genome Sequence of Thalassospira sp. Strain KO164 Isolated from a
      Lignin-Enriched Marine Sediment Microcosm.
AB  - Thalassospira sp. strain KO164 was isolated from eastern Mediterranean seawater
      and sediment laboratory microcosms enriched on insoluble organosolv lignin under
      oxic conditions. The near-complete genome sequence presented here will facilitate
      analyses into this deep-ocean bacterium's ability to degrade recalcitrant
      organics such as lignin.

PMID- 27881539
TI  - Coexistence of Fosfomycin and Colistin Resistance in Klebsiella pneumoniae: Whole
      Genome Shotgun Sequencing.
AB  - Resistance to colistin is a major threat that limits therapeutic choices for
      treating carbapenem-resistant Klebsiella pneumoniae infections. Herein, we report
      the draft genome sequences of two colistin-resistant K. pneumoniae isolates
      (BA41763 and B6753). The sequence data indicate that BA41763 and B6753 contain
      genomes of ~5.9 and 5.7 Mb in size with several plasmids.

PMID- 27881541
TI  - Whole-Genome Sequences of Two Manganese(II)-Oxidizing Bacteria, Bosea sp. Strain
      BIWAKO-01 and Alphaproteobacterium Strain U9-1i.
AB  - This report describes the whole-genome sequences of two Mn(II)-oxidizing
      bacteria, filamentous Mn oxide microparticle-forming Bosea sp. strain BIWAKO-01
      and alphaproteobacterium strain U9-1i.

PMID- 27881540
TI  - Genome Sequence of Salegentibacter salarius KCTC 12974, Isolated from a Marine
      Solar Saltern of the Yellow Sea in South Korea.
AB  - Salegentibacter salarius KCTC 12974 is isolated from a marine solar saltern of
      the Yellow Sea in South Korea. Here, we report the draft genome sequence of
      Salegentibacter salarius KCTC 12974. Various glycoside hydrolase genes in even
      numbers in the genome reflect the ecological adaption of KCTC 12974 to its
      habitat.

PMID- 27881543
TI  - First Report on the Draft Genome Sequences of Corynebacterium diphtheriae
      Isolates from India.
AB  - We report here the draft genome sequences of five Corynebacterium diphtheriae
      isolates of Indian origin. The C. diphtheriae isolates TH1141, TH510, TH1526,
      TH1337, and TH2031 belong to sequence type ST-50, ST-295, ST-377, ST-405, and ST
      405, with an average genome size of 2.5 Mbp.

PMID- 27881542
TI  - Draft Genome Sequences of Four Alteromonas macleodii Strains Isolated from Copper
      Coupons and Grown Long-Term at Elevated Copper Levels.
AB  - Alteromonas macleodii is a marine bacterium involved in the early stages of
      biofouling on ship hulls treated with copper as an antifouling agent. We report
      here the draft genome sequences of an A. macleodii strain isolated from copper
      coupons and three laboratory mutants grown long-term at elevated copper levels.

PMID- 27881544
TI  - Draft Genome Sequence of Lysinibacillus xylanilyticus SR-86.
AB  - Lysinibacillus xylanilyticus belongs to the family Bacillaceae and was first
      described in 2010 with the type strain L. xylanilyticus XDB9. It is able to both
      degrade xylan and use it as the sole carbon source. Here, we describe the 4.8-Mb
      genome of the strain L. xylanilyticus SR-86, which was isolated from organic
      waste.

PMID- 27881545
TI  - Complete Genome Sequence of the Probiotic Strain Lactobacillus salivarius LPM01.
AB  - Lactobacillus salivarius LPM01 (DSM 22150) is a probiotic strain able to improve
      health status in immunocompromised people. Here, we report its complete genome
      sequence deciphered by PacBio single-molecule real-time (SMRT) technology.
      Analysis of the sequence may provide insights into its functional activity and
      safety assessment.

PMID- 27881546
TI  - Draft Genome Sequences of Two "Haemophilus quentini" Isolates Recovered from Two
      Different Patients' Blood Cultures.
AB  - Here, we present the draft genome sequences of two strains (K068 and C860) of the
      genospecies "Haemophilus quentini" The isolates were recovered from blood
      cultures of a newborn neonate and an elderly patient with septicemia in Ontario,
      Canada.

PMID- 27881548
TI  - Draft Genome Sequence of Lactobacillus plantarum TL2766, a Strain with the
      Ability To Ferment Wakame.
AB  - The genome sequence of Lactobacillus plantarum TL2766, a strain with the ability
      to ferment wakame (Undaria pinnatifida), is described here. The reads were
      assembled into contigs, with a total size of 3,310,195 bp. The genome information
      will be useful for further specific genetic studies of this strain and for its
      biotechnological applications.

PMID- 27881547
TI  - Draft Genome Sequence of Salmonella enterica subsp. diarizonae Serovar
      61:k:1,5,(7) Strain CRJJGF_00165 (Phylum Gammaproteobacteria).
AB  - Here, we report a 4.78-Mb draft genome sequence of the Salmonella enterica subsp.
      diarizonae serovar 61:k:1,5,(7) strain CRJJGF_00165 [also called S. enterica
      subsp. IIIb serovar 61:k:1,5,(7) strain CRJJGF_00165], isolated from ground beef
      in 2007.

PMID- 27881549
TI  - Genome Sequence of Corynebacterium pseudotuberculosis Strain XH02 Isolated from a
      Boer Goat in Xuanhan, China.
AB  - We report here the genome sequence of Corynebacterium pseudotuberculosis strain
      XH02, isolated from a Boer goat in China. The genome consists of 2,357,671 bp,
      with a 52.18% G+C content, 2,263 coding sequences, 21 rRNAs, 49 tRNAs, and 44
      predicted pseudogenes.

PMID- 27881550
TI  - Draft Genome Sequence of Magnetovibrio blakemorei Strain MV-1, a Marine Vibrioid
      Magnetotactic Bacterium.
AB  - We report here the genome sequence of Magnetovibrio blakemorei MV-1, a marine
      vibrioid magnetotactic bacterium with a single polar flagellum. The current
      assembly consists of 91 contigs with a combined size of 3,638,804 bp (54.3% G+C
      content). This genome allows for further investigations of the molecular
      biomineralization mechanisms of magnetosome formation.

PMID- 27881551
TI  - Comparison of the Otto Bock solid ankle cushion heel foot with wooden keel to the
      low-cost CR-EquipementsTM solid ankle cushion heel foot with polypropylene keel:
      A randomized prospective double-blind crossover study assessing patient
      satisfaction and energy expenditure.
AB  - BACKGROUND: The International Committee of the Red Cross supports a worldwide
      program of prosthetic fitting and rehabilitation. In this context, a prosthetic
      foot was developed and widely distributed in least developed countries. STUDY
      DESIGN: Prospective, randomized, double-blind, controlled study. OBJECTIVE: To
      compare patient satisfaction and energy expenditure during ambulation between a
      low-cost prosthetic foot designed with a polypropylene keel (CR-EquipementsTM
      solid ankle cushion heel, International Committee of the Red Cross) to a well
      recognized solid ankle cushion heel foot with a wooden keel (solid ankle cushion
      heel foot, Otto Bock). METHODS: A total of 15 participants with unilateral
      transtibial amputation were evaluated using the two prosthetic feet in a
      randomized prospective double-blind crossover study. Main outcomes were patient
      satisfaction questionnaires (Satisfaction with Prosthesis Questionnaire and
      prosthetic foot satisfaction) and energy expenditure (oxygen consumption
      mL/kg/min, oxygen cost-mL/kg/m, and heart rate-bpm). RESULTS: There were no
      significant differences between the two prosthetic feet for satisfaction and
      energy expenditure. CONCLUSION: The low-cost solid ankle cushion heel foot with
      polypropylene keel provides comparable satisfaction and similar energy
      expenditure as the solid ankle cushion heel foot with wooden keel. Clinical
      relevance The results of this study support the application and widespread use of
      the CR-EquipementsTM solid ankle cushion heel foot. From a cost-effectiveness
      standpoint, patients are well satisfied and exhibit similar outcomes at a
      substantially lower cost.

PMID- 27881554
TI  - O PIONEERs! The Beginning of the End of Full-Dose Triple Therapy with Warfarin?

PMID- 27881553
TI  - Stage-Specific Transcriptome and Proteome Analyses of the Filarial Parasite
      Onchocerca volvulus and Its Wolbachia Endosymbiont.
AB  - : Onchocerciasis (river blindness) is a neglected tropical disease that has been
      successfully targeted by mass drug treatment programs in the Americas and small
      parts of Africa. Achieving the long-term goal of elimination of onchocerciasis,
      however, requires additional tools, including drugs, vaccines, and biomarkers of
      infection. Here, we describe the transcriptome and proteome profiles of the major
      vector and the human host stages (L1, L2, L3, molting L3, L4, adult male, and
      adult female) of Onchocerca volvulus along with the proteome of each parasitic
      stage and of its Wolbachia endosymbiont (wOv). In so doing, we have identified
      stage-specific pathways important to the parasite's adaptation to its human host
      during its early development. Further, we generated a protein array that, when
      screened with well-characterized human samples, identified novel diagnostic
      biomarkers of O. volvulus infection and new potential vaccine candidates. This
      immunomic approach not only demonstrates the power of this postgenomic discovery
      platform but also provides additional tools for onchocerciasis control programs.
      IMPORTANCE: The global onchocerciasis (river blindness) elimination program will
      have to rely on the development of new tools (drugs, vaccines, biomarkers) to
      achieve its goals by 2025. As an adjunct to the completed genomic sequencing of
      O. volvulus, we used a comprehensive proteomic and transcriptomic profiling
      strategy to gain a comprehensive understanding of both the vector-derived and
      human host-derived parasite stages. In so doing, we have identified proteins and
      pathways that enable novel drug targeting studies and the discovery of novel
      vaccine candidates, as well as useful biomarkers of active infection.

PMID- 27881552
TI  - Cardiac T-Tubule Microanatomy and Function.
AB  - Unique to striated muscle cells, transverse tubules (t-tubules) are membrane
      organelles that consist of sarcolemma penetrating into the myocyte interior,
      forming a highly branched and interconnected network. Mature t-tubule networks
      are found in mammalian ventricular cardiomyocytes, with the transverse components
      of t-tubules occurring near sarcomeric z-discs. Cardiac t-tubules contain
      membrane microdomains enriched with ion channels and signaling molecules. The
      microdomains serve as key signaling hubs in regulation of cardiomyocyte function.
      Dyad microdomains formed at the junctional contact between t-tubule membrane and
      neighboring sarcoplasmic reticulum are critical in calcium signaling and
      excitation-contraction coupling necessary for beat-to-beat heart contraction. In
      this review, we provide an overview of the current knowledge in gross morphology
      and structure, membrane and protein composition, and function of the cardiac t
      tubule network. We also review in detail current knowledge on the formation of
      functional membrane subdomains within t-tubules, with a particular focus on the
      cardiac dyad microdomain. Lastly, we discuss the dynamic nature of t-tubules
      including membrane turnover, trafficking of transmembrane proteins, and the life
      cycles of membrane subdomains such as the cardiac BIN1-microdomain, as well as t
      tubule remodeling and alteration in diseased hearts. Understanding cardiac t
      tubule biology in normal and failing hearts is providing novel diagnostic and
      therapeutic opportunities to better treat patients with failing hearts.

PMID- 27881555
TI  - Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing
      Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a
      Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy.
AB  - BACKGROUND: Patients with atrial fibrillation who undergo intracoronary stenting
      traditionally are treated with a vitamin K antagonist (VKA) plus dual
      antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding.
      We hypothesized that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy
      or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable
      impact on all-cause mortality and the need for rehospitalization. METHODS:
      Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized
      1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y12
      inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with
      stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group
      2); or the reference arm of dose-adjusted VKA daily with a similar DAPT
      stratification (group 3). The present post hoc analysis assessed the end point of
      all-cause mortality or recurrent hospitalization for an adverse event, which was
      further classified as the result of bleeding, a cardiovascular cause, or another
      cause blinded to treatment assignment. RESULTS: The risk of all-cause mortality
      or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95%
      confidence interval, 0.66-0.94; P=0.008 versus group 3; number needed to
      treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62
      0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3
      (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from
      bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus
      group 3], and group 3=12.4%) and all-cause death plus rehospitalization
      potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus
      group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced
      in the rivaroxaban arms compared with the VKA arm, but other forms of
      rehospitalization were not. CONCLUSIONS: Among patients with atrial fibrillation
      undergoing intracoronary stenting, administration of either rivaroxaban 15 mg
      daily plus P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus
      DAPT was associated with a reduced risk of all-cause mortality or recurrent
      hospitalization for adverse events compared with standard-of-care VKA plus DAPT.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01830543.

PMID- 27881556
TI  - Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral
      Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia.
AB  - BACKGROUND: The mechanisms underlying red blood cell (RBC)-mediated hypoxic
      vasodilation remain controversial, with separate roles for nitrite () and S
      nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce
      nitric oxide bioactivity within the microcirculation. To establish their relative
      contribution in vivo, we quantified arterial-venous concentration gradients
      across the human cerebral and femoral circulation at rest and during exercise, an
      ideal model system characterized by physiological extremes of O2 tension and
      blood flow. METHODS: Ten healthy participants (5 men, 5 women) aged 24+/-4
      (mean+/-SD) years old were randomly assigned to a normoxic (21% O2) and hypoxic
      (10% O2) trial with measurements performed at rest and after 30 minutes of
      cycling at 70% of maximal power output in hypoxia and equivalent relative and
      absolute intensities in normoxia. Blood was sampled simultaneously from the
      brachial artery and internal jugular and femoral veins with plasma and RBC nitric
      oxide metabolites measured by tri-iodide reductive chemiluminescence. Blood flow
      was determined by transcranial Doppler ultrasound (cerebral blood flow) and
      constant infusion thermodilution (femoral blood flow) with net exchange
      calculated via the Fick principle. RESULTS: Hypoxia was associated with a mild
      increase in both cerebral blood flow and femoral blood flow (P<0.05 versus
      normoxia) with further, more pronounced increases observed in femoral blood flow
      during exercise (P<0.05 versus rest) in proportion to the reduction in RBC
      oxygenation (r=0.680-0.769, P<0.001). Plasma gradients reflecting consumption
      (arterial>venous; P<0.05) were accompanied by RBC iron nitrosylhemoglobin
      formation (venous>arterial; P<0.05) at rest in normoxia, during hypoxia (P<0.05
      versus normoxia), and especially during exercise (P<0.05 versus rest), with the
      most pronounced gradients observed across the bioenergetically more active,
      hypoxemic, and acidotic femoral circulation (P<0.05 versus cerebral). In
      contrast, we failed to observe any gradients consistent with RBC SNO-Hb
      consumption and corresponding delivery of plasma S-nitrosothiols (P>0.05).
      CONCLUSIONS: These findings suggest that hypoxia and, to a far greater extent,
      exercise independently promote arterial-venous delivery gradients of
      intravascular nitric oxide, with deoxyhemoglobin-mediated reduction identified as
      the dominant mechanism underlying hypoxic vasodilation.

PMID- 27881558
TI  - The American Heart Association's New Institute for Precision Cardiovascular
      Medicine.

PMID- 27881557
TI  - Plasma Metabolomics Implicates Modified Transfer RNAs and Altered Bioenergetics
      in the Outcomes of Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a heterogeneous disorder
      with high mortality. METHODS: We conducted a comprehensive study of plasma
      metabolites using ultraperformance liquid chromatography mass spectrometry to
      identify patients at high risk of early death, to identify patients who respond
      well to treatment, and to provide novel molecular insights into disease
      pathogenesis. RESULTS: Fifty-three circulating metabolites distinguished well
      phenotyped patients with idiopathic or heritable PAH (n=365) from healthy control
      subjects (n=121) after correction for multiple testing (P<7.3e-5) and confounding
      factors, including drug therapy, and renal and hepatic impairment. A subset of 20
      of 53 metabolites also discriminated patients with PAH from disease control
      subjects (symptomatic patients without pulmonary hypertension, n=139). Sixty-two
      metabolites were prognostic in PAH, with 36 of 62 independent of established
      prognostic markers. Increased levels of tRNA-specific modified nucleosides (N2,N2
      dimethylguanosine, N1-methylinosine), tricarboxylic acid cycle intermediates
      (malate, fumarate), glutamate, fatty acid acylcarnitines, tryptophan, and
      polyamine metabolites and decreased levels of steroids, sphingomyelins, and
      phosphatidylcholines distinguished patients from control subjects. The largest
      differences correlated with increased risk of death, and correction of several
      metabolites over time was associated with a better outcome. Patients who
      responded to calcium channel blocker therapy had metabolic profiles similar to
      those of healthy control subjects. CONCLUSIONS: Metabolic profiles in PAH are
      strongly related to survival and should be considered part of the deep phenotypic
      characterization of this disease. Our results support the investigation of
      targeted therapeutic strategies that seek to address the alterations in
      translational regulation and energy metabolism that characterize these patients.

PMID- 27881559
TI  - Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived
      Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I
      Event Reducing in Ischemic Syndromes I).
AB  - BACKGROUND: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to
      increase high-density lipoprotein-mediated cholesterol efflux capacity and to
      regress atherosclerotic disease in animal and clinical studies. CSL112 is an
      infusible, plasma-derived apoA-I that has been studied in normal subjects or
      those with stable coronary artery disease. This study aimed to characterize the
      safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in
      patients with a recent acute myocardial infarction. METHODS: The AEGIS-I trial
      (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized,
      double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with
      myocardial infarction were stratified by renal function and randomized 1:1:1 to
      CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or
      placebo for 4 consecutive weekly infusions. Coprimary safety end points were
      occurrence of either a hepatic safety event (an increase in alanine transaminase
      >3 times the upper limit of normal or an increase in total bilirubin >2 times the
      upper limit of normal) or a renal safety event (an increase in serum creatinine
      >1.5 times the baseline value or a new requirement for renal replacement
      therapy). RESULTS: A total of 1258 patients were randomized, and 91.2% received
      all 4 infusions. The difference in incidence rates for an increase in alanine
      transaminase or total bilirubin between both CSL112 arms and placebo was within
      the protocol-defined noninferiority margin of 4%. Similarly, the difference in
      incidence rates for an increase in serum creatinine or a new requirement for
      renal replacement therapy was within the protocol-defined noninferiority margin
      of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol
      efflux similar to that achieved in patients with stable coronary artery disease.
      In regard to the secondary efficacy end point, the risk for the composite of
      major adverse cardiovascular events among the groups was similar. CONCLUSIONS:
      Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are
      feasible, well tolerated, and not associated with any significant alterations in
      liver or kidney function or other safety concern. The ability of CSL112 to
      acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112
      to reduce major adverse cardiovascular events needs to be assessed in an
      adequately powered phase 3 trial. CLINICAL TRIAL REGISTRATION: URL:
      https://clinicaltrials.gov. Unique identifier: NCT02108262.

PMID- 27881561
TI  - Reassessment of Cardiac Function and Implantable Cardioverter-Defibrillator Use
      Among Medicare Patients With Low Ejection Fraction After Myocardial Infarction.
AB  - BACKGROUND: Guidelines recommend that patients with low ejection fraction (EF)
      after myocardial infarction (MI) have their EF reassessed 40 days after MI for
      implantable cardioverter-defibrillator (ICD) candidacy. This study examines rates
      of EF reassessment and their association with 1-year ICD implantation in post-MI
      patients with low EF. METHODS: We examined rates of postdischarge EF reassessment
      and ICD implantation among 10 289 Medicare-insured patients >=65 years of age
      with an EF<=35% during the index MI admission from January 2007 through September
      2010 in ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes
      Network Registry-Get With The Guidelines). Multivariable Cox models tested the
      association between time-dependent EF reassessment and 1-year ICD implantation,
      stratified by revascularization status during the index MI admission. RESULTS:
      Among patients with EF <=35% during the index MI admission, 66.8% (95% confidence
      interval [CI], 65.9-67.8) had EF reassessment within the next year.
      Revascularized patients were more likely to have EF reassessment (76.9% [95% CI,
      75.8-78.0)] versus 53.7% [95% CI, 52.2-55.2]; P<0.001) and had shorter times to
      EF reassessment (median, 67 versus 84 days; P<0.001) than nonrevascularized
      patients. Among patients with EF reassessment, only 11% received an ICD within 1
      year. Reassessment of EF was associated with a higher likelihood of ICD
      implantation for both revascularized (unadjusted, 12.1% versus 2.4%, P<0.001;
      adjusted hazard ratio, 10.6, 95% CI, 7.7-14.8) and nonrevascularized (unadjusted,
      10.0% versus 1.7%, P<0.001; adjusted hazard ratio, 6.1, 95% CI, 4.1-9.2)
      patients. CONCLUSIONS: In US practice, EF reassessments are commonly performed
      among patients with MI with an initially reduced EF. Although 1-year EF
      reassessment is associated with increased likelihood of ICD implantation, 1-year
      ICD implantation rates remain very low even among patients with EF reassessment,
      regardless of revascularization status.

PMID- 27881560
TI  - Coronary Artery Calcium to Guide a Personalized Risk-Based Approach to Initiation
      and Intensification of Antihypertensive Therapy.
AB  - BACKGROUND: The use of atherosclerotic cardiovascular disease (ASCVD) risk to
      personalize systolic blood pressure (SBP) treatment goals is a topic of
      increasing interest. Therefore, we studied whether coronary artery calcium (CAC)
      can further guide the allocation of anti-hypertensive treatment intensity.
      METHODS: We included 3733 participants from the Multi-Ethnic Study of
      Atherosclerosis (MESA) with SBP between 120 and 179 mm Hg. Within subgroups
      categorized by both SBP (120-139 mm Hg, 140-159 mm Hg, and 160-179 mm Hg) and
      estimated 10-year ASCVD risk (using the American College of Cardiology/American
      Heart Assocation pooled-cohort equations), we compared multivariable-adjusted
      hazard ratios for the composite outcome of incident ASCVD or heart failure after
      further stratifying by CAC (0, 1-100, or >100). We estimated 10-year number
      needed-to-treat for an intensive SBP goal of 120 mm Hg by applying the treatment
      benefit recorded in meta-analyses to event rates within CAC strata. RESULTS: The
      mean age was 65 years, and 642 composite events took place over a median of 10.2
      years. In persons with SBP <160 mm Hg, CAC stratified risk for events. For
      example, among those with an ASCVD risk of <15% and who had an SBP of either 120
      to 139 mm Hg or 140 to 159 mm Hg, respectively, we found increasing hazard ratios
      for events with CAC 1 to 100 (1.7 [95% confidence interval, 1.0-2.6] or 2.0 [1.1
      3.8]) and CAC >100 (3.0 [1.8-5.0] or 5.7 [2.9-11.0]), all relative to CAC=0.
      There appeared to be no statistical association between CAC and events when SBP
      was 160 to 179 mm Hg, irrespective of ASCVD risk level. Estimated 10-year number
      needed-to-treat for a SBP goal of 120mmHg varied substantially according to CAC
      levels when predicted ASCVD risk <15% and SBP <160mmHg (eg, 10-year number-needed
      to-treat of 99 for CAC=0 and 24 for CAC>100, when SBP 120-139mm Hg). However, few
      participants with ASCVD risk <5% had elevated CAC. Furthermore, 10-year number
      needed-to-treat estimates were consistently low and varied less among CAC strata
      when SBP was 160 to 179 mm Hg or when ASCVD risk was >=15% at any SBP level.
      CONCLUSIONS: Combined CAC imaging and assessment of global ASCVD risk has the
      potential to guide personalized SBP goals (eg, choosing a traditional goal of 140
      or a more intensive goal of 120 mm Hg), particularly among adults with an
      estimated ASCVD risk of 5% to 15% and prehypertension or mild hypertension.

PMID- 27881562
TI  - Total Anomalous Pulmonary Venous Connection: The Current Management Strategies in
      a Pediatric Cohort of 768 Patients.
AB  - BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare form of
      congenital heart disease. This study describes current surgical treatment
      strategies and experiences in a cohort of patients from 2 congenital cardiac
      centers in Shanghai and Guangdong in China. METHODS: This retrospective study
      included 768 patients operated on between 2005 and 2014. Although most patients
      (n=690) underwent conventional repair, a sutureless technique was used in 10%
      (n=78) of cases. A multilevel mixed-effects parametric survival model and a
      competing-risk analysis were used to analyze associated risk factors for death
      and recurrent pulmonary venous obstruction (PVO), respectively. Kaplan-Meier
      analysis was used to analyze the overall survival. The Nelson-Aalen cumulative
      risk curve was used to compare distributions of time with recurrent PVO. RESULTS:
      The mean surgical age and weight were 214.9+/-39.2 days and 5.4+/-3.6 kg,
      respectively. Obstructed TAPVC (PVO) was documented in 192 (25%) of the 768
      patients. There were 38 intraoperative deaths and 13 late deaths. A younger age
      at the time of repair (P=0.001), mixed (P=0.004) and infracardiac (P=0.035)
      TAPVC, preoperative PVO (P=0.027), prolonged cardiopulmonary bypass time
      (P<0.001), and longer duration of ventilation (P=0.028) were associated with
      mortality. The median follow-up was 23.2 months (range; 1-112 months). Among the
      717 survivors, recurrent PVO was observed in 111 patients (15%). Associated risk
      factors for recurrent PVO included preoperative PVO (P<0.001), infracardiac TAPVC
      (P<0.001), mixed TAPVC (P=0.013), and prolonged cardiopulmonary bypass time
      (P<0.001). Sutureless technique was associated with a lower restenosis rate
      compared with conventional repair in patients with preoperative PVO (P=0.038),
      except in newborn patients (P=0.443). Reintervention for restenosis was performed
      in 24 patients. The function of most survivors (91%) was classified according to
      the New York Heart Association as functional class I or II. CONCLUSIONS: Surgical
      correction in patients with TAPVC with a biventricular anatomy can achieve an
      acceptable outcome. Risk factors such as a younger age at the time of repair,
      infracardiac and mixed TAPVC, and preoperative PVO were associated with a poorer
      prognosis.

PMID- 27881563
TI  - Conventional Versus Compression-Only Versus No-Bystander Cardiopulmonary
      Resuscitation for Pediatric Out-of-Hospital Cardiac Arrest.
AB  - BACKGROUND: Conventional cardiopulmonary resuscitation (CPR) (chest compression
      and rescue breathing) has been recommended for pediatric out-of-hospital cardiac
      arrest (OHCA) because of the asphyxial nature of the majority of pediatric
      cardiac arrest events. However, the clinical effectiveness of additional rescue
      breathing (conventional CPR) compared with compression-only CPR in children is
      uncertain. METHODS: This nationwide population-based study of pediatric OHCA
      patients was based on data from the All-Japan Utstein Registry. We included all
      pediatric patients who experienced OHCA in Japan from January 1, 2011, to
      December 31, 2012. The primary outcome was a favorable neurological state 1 month
      after OHCA defined as a Glasgow-Pittsburgh Cerebral Performance Category score of
      1 to 2 (corresponding to a Pediatric Cerebral Performance Category score of 1-3).
      Outcomes were compared with logistic regression with uni- and multivariable
      modeling in the overall cohort and for a propensity-matched subset of patients.
      RESULTS: A total of 2157 patients were included; 417 received conventional CPR,
      733 received compression-only CPR, and 1007 did not receive any bystander CPR.
      Among these patients, 213 (9.9%) survived with a favorable neurological status 1
      month after OHCA, including 108/417 (25.9%) for conventional, 68/733 (9.3%) for
      compression-only, and 37/1007 (3.7%) for no-bystander CPR. In unadjusted
      analyses, conventional CPR was superior to compression-only CPR in neurologically
      favorable survival (odds ratio [OR] 3.42, 95% confidence interval [CI] 2.45-4.76;
      P<0.0001), with a trend favoring conventional CPR that was no longer
      statistically significant after multivariable adjustment (ORadjusted 1.52, 95% CI
      0.93-2.49), and with further attenuation of the difference in a propensity
      matched subset (OR 1.20, 95% CI 0.81-1.77). Both conventional and compression
      only CPR were associated with higher odds for neurologically favorable survival
      compared with no-bystander CPR (ORadjusted 5.01, 95% CI 2.98-8.57, and ORadjusted
      3.29, 95% CI 1.93-5.71), respectively. CONCLUSIONS: In this population-based
      study of pediatric OHCA in Japan, both conventional and compression-only CPR were
      associated with superior outcomes compared with no-bystander CPR. Unadjusted
      outcomes with conventional CPR were superior to compression-only CPR, with the
      magnitude of difference attenuated and no longer statistically significant after
      statistical adjustments. These findings support randomized clinical trials
      comparing conventional versus compression-only CPR in children, with conventional
      CPR preferred until such controlled comparative data are available, and either
      method preferred over no-bystander CPR.

PMID- 27881564
TI  - Heart Failure Stages Among Older Adults in the Community: The Atherosclerosis
      Risk in Communities Study.
AB  - BACKGROUND: Although heart failure (HF) disproportionately affects older adults,
      little data exist regarding the prevalence of American College of
      Cardiology/American Heart Association HF stages among older individuals in the
      community. Additionally, the role of contemporary measures of longitudinal strain
      and diastolic dysfunction in defining HF stages is unclear. METHODS: HF stages
      were classified in 6118 participants in the Atherosclerosis Risk in Communities
      study (67-91 years of age) at the fifth study visit as follows: A (asymptomatic
      with HF risk factors but no cardiac structural or functional abnormalities), B
      (asymptomatic with structural abnormalities, defined as left ventricular
      hypertrophy, dilation or dysfunction, or significant valvular disease), C1
      (clinical HF without prior hospitalization), and C2 (clinical HF with earlier
      hospitalization). RESULTS: Using the traditional definitions of HF stages, only
      5% of examined participants were free of HF risk factors or structural heart
      disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and
      6% Stage C2. Worse HF stage was associated with a greater risk of incident HF
      hospitalization or death at a median follow-up of 608 days. Left ventricular (LV)
      ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively.
      Incorporation of longitudinal strain and diastolic dysfunction into the Stage B
      definition reclassified 14% of the sample from Stage A to B and improved the net
      reclassification index (P=0.028) and integrated discrimination index (P=0.016).
      Abnormal LV structure, systolic function (based on LV ejection fraction and
      longitudinal strain), and diastolic function (based on e', E/e', and left atrial
      volume index) were each independently and additively associated with risk of
      incident HF hospitalization or death in Stage A and B participants. CONCLUSIONS:
      The majority of older adults in the community are at risk for HF (Stages A or B),
      appreciably more compared with previous reports in younger community-based
      samples. LV ejection fraction is robustly preserved in at least two-thirds of
      older adults with prevalent HF (Stage C), highlighting the burden of HF with
      preserved LV ejection fraction in the elderly. LV diastolic function and
      longitudinal strain provide incremental prognostic value beyond conventional
      measures of LV structure and LV ejection fraction in identifying persons at risk
      for HF hospitalization or death.

PMID- 27881565
TI  - Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With
      Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial.
AB  - BACKGROUND: The long-term efficacy and safety of low-dose aspirin for primary
      prevention of cardiovascular events in patients with type 2 diabetes mellitus are
      still inconclusive. METHODS: The JPAD trial (Japanese Primary Prevention of
      Atherosclerosis With Aspirin for Diabetes) was a randomized, open-label, standard
      care-controlled trial examining whether low-dose aspirin affected cardiovascular
      events in 2539 Japanese patients with type 2 diabetes mellitus and without
      preexisting cardiovascular disease. Patients were randomly allocated to receive
      aspirin (81 or 100 mg daily; aspirin group) or no aspirin (no-aspirin group) in
      the JPAD trial. After that trial ended in 2008, we followed up with the patients
      until 2015, with no attempt to change the previously assigned therapy. Primary
      end points were cardiovascular events, including sudden death, fatal or nonfatal
      coronary artery disease, fatal or nonfatal stroke, and peripheral vascular
      disease. For the safety analysis, hemorrhagic events, consisting of
      gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites,
      were also analyzed. The primary analysis was conducted for cardiovascular events
      among patients who retained their original allocation (a per-protocol cohort).
      Analyses on an intention-to-treat cohort were conducted for hemorrhagic events
      and statistical sensitivity. RESULTS: The median follow-up period was 10.3 years;
      1621 patients (64%) were followed up throughout the study; and 2160 patients
      (85%) retained their original allocation. Low-dose aspirin did not reduce
      cardiovascular events in the per-protocol cohort (hazard ratio, 1.14; 95%
      confidence interval, 0.91-1.42). Multivariable Cox proportional hazard model
      adjusted for age, sex, glycemic control, kidney function, smoking status,
      hypertension, and dyslipidemia showed similar results (hazard ratio, 1.04; 95%
      confidence interval, 0.83-1.30), with no heterogeneity of efficacy in subgroup
      analyses stratified by each of these factors (all interaction P>0.05).
      Sensitivity analyses on the intention-to-treat cohort yielded consistent results
      (hazard ratio, 1.01; 95% confidence interval, 0.82-1.25). Gastrointestinal
      bleeding occurred in 25 patients (2%) in the aspirin group and 12 (0.9%) in the
      no-aspirin group (P=0.03), and the incidence of hemorrhagic stroke was not
      different between groups. CONCLUSIONS: Low-dose aspirin did not affect the risk
      for cardiovascular events but increased risk for gastrointestinal bleeding in
      patients with type 2 diabetes mellitus in a primary prevention setting. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00110448.

PMID- 27881566
TI  - Association of Bystander Cardiopulmonary Resuscitation and Survival According to
      Ambulance Response Times After Out-of-Hospital Cardiac Arrest.
AB  - BACKGROUND: Bystander-initiated cardiopulmonary resuscitation (CPR) increases
      patient survival after out-of-hospital cardiac arrest, but it is unknown to what
      degree bystander CPR remains positively associated with survival with increasing
      time to potential defibrillation. The main objective was to examine the
      association of bystander CPR with survival as time to advanced treatment
      increases. METHODS: We studied 7623 out-of-hospital cardiac arrest patients
      between 2005 and 2011, identified through the nationwide Danish Cardiac Arrest
      Registry. Multiple logistic regression analysis was used to examine the
      association between time from 911 call to emergency medical service arrival
      (response time) and survival according to whether bystander CPR was provided (yes
      or no). Reported are 30-day survival chances with 95% bootstrap confidence
      intervals. RESULTS: With increasing response times, adjusted 30-day survival
      chances decreased for both patients with bystander CPR and those without.
      However, the contrast between the survival chances of patients with versus
      without bystander CPR increased over time: within 5 minutes, 30-day survival was
      14.5% (95% confidence interval [CI]: 12.8-16.4) versus 6.3% (95% CI: 5.1-7.6),
      corresponding to 2.3 times higher chances of survival associated with bystander
      CPR; within 10 minutes, 30-day survival chances were 6.7% (95% CI: 5.4-8.1)
      versus 2.2% (95% CI: 1.5-3.1), corresponding to 3.0 times higher chances of 30
      day survival associated with bystander CPR. The contrast in 30-day survival
      became statistically insignificant when response time was >13 minutes (bystander
      CPR vs no bystander CPR: 3.7% [95% CI: 2.2-5.4] vs 1.5% [95% CI: 0.6-2.7]), but
      30-day survival was still 2.5 times higher associated with bystander CPR. Based
      on the model and Danish out-of-hospital cardiac arrest statistics, an additional
      233 patients could potentially be saved annually if response time was reduced
      from 10 to 5 minutes and 119 patients if response time was reduced from 7 (the
      median response time in this study) to 5 minutes. CONCLUSIONS: The absolute
      survival associated with bystander CPR declined rapidly with time. Yet bystander
      CPR while waiting for an ambulance was associated with a more than doubling of 30
      day survival even in case of long ambulance response time. Decreasing ambulance
      response time by even a few minutes could potentially lead to many additional
      lives saved every year.

PMID- 27881567
TI  - Importance of Assessing Cardiorespiratory Fitness in Clinical Practice: A Case
      for Fitness as a Clinical Vital Sign: A Scientific Statement From the American
      Heart Association.
AB  - Mounting evidence has firmly established that low levels of cardiorespiratory
      fitness (CRF) are associated with a high risk of cardiovascular disease, all
      cause mortality, and mortality rates attributable to various cancers. A growing
      body of epidemiological and clinical evidence demonstrates not only that CRF is a
      potentially stronger predictor of mortality than established risk factors such as
      smoking, hypertension, high cholesterol, and type 2 diabetes mellitus, but that
      the addition of CRF to traditional risk factors significantly improves the
      reclassification of risk for adverse outcomes. The purpose of this statement is
      to review current knowledge related to the association between CRF and health
      outcomes, increase awareness of the added value of CRF to improve risk
      prediction, and suggest future directions in research. Although the statement is
      not intended to be a comprehensive review, critical references that address
      important advances in the field are highlighted. The underlying premise of this
      statement is that the addition of CRF for risk classification presents health
      professionals with unique opportunities to improve patient management and to
      encourage lifestyle-based strategies designed to reduce cardiovascular risk.
      These opportunities must be realized to optimize the prevention and treatment of
      cardiovascular disease and hence meet the American Heart Association's 2020
      goals.

PMID- 27881568
TI  - Incident Type 2 Myocardial Infarction in a Cohort of Patients Undergoing Coronary
      or Peripheral Arterial Angiography.
AB  - BACKGROUND: Despite growing recognition of type 2 myocardial infarction (T2MI;
      related to supply/demand mismatch), little is known about its risk factors or its
      association with outcome. METHODS: A single-center cohort of patients undergoing
      coronary or peripheral angiography with or without intervention was prospectively
      enrolled and followed for incident type 1 and T2MI, and major adverse
      cardiovascular events (MACE, a composite of all-cause death, nonfatal myocardial
      infarction [MI], heart failure, stroke, transient ischemic attack, peripheral
      arterial complication, and cardiac arrhythmia), as well. T2MI was adjudicated
      using criteria from the Third Universal Definition of MI. Baseline
      characteristics, blood samples, and angiography information were obtained. Major
      end points subsequent to first MI were assessed using landmark analyses to
      compare the rates of first events only where everyone with a prior history of any
      MACE before MI were censored and adjusted for follow-up times. Cox proportional
      hazard models were used for time-to-event analyses with age and sex forced into
      all models and additional covariates evaluated by using the stepwise option for
      the selection. RESULTS: One thousand two hundred fifty-one patients were enrolled
      and followed for a median of 3.4 years. Of these patients, 152 (12.2%) had T2MI
      during follow-up; T2MI was frequently recurrent. Multivariable predictors of T2MI
      were older age, lower systolic blood pressure, history of coronary artery
      disease, heart failure, chronic obstructive pulmonary disease, diabetes mellitus,
      nitrate use, and elevated concentrations of glucose, N-terminal pro-B type
      natriuretic peptide, and cystatin C. Patients with T2MI had higher rates of
      subsequent adverse events than those without T2MI (per 100 person-years: MACE,
      53.7 versus 21.1, P<0.001; all-cause death, 23.3 versus 3.3, P<0.001;
      cardiovascular death, 17.5 versus 2.6, P<0.001; heart failure events, 22.4 versus
      7.4, P<0.001); these rates are similar to those seen in patients with type 1 MI.
      Incident diagnosis of T2MI strongly predicted risk for subsequent MACE (adjusted
      hazard ratio, 1.90; 95% confidence interval, 1.46-2.48; P<0.001), all-cause death
      (adjusted hazard ratio, 2.96; 95% confidence interval, 2.01-4.36; P<0.001), and
      cardiovascular death (adjusted hazard ratio, 2.16; 95% confidence interval, 1.36
      3.43; P=0.001). CONCLUSIONS: T2MI is common and associated with poor prognosis.
      Studies evaluating treatment strategies for management of T2MI are needed.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00842868.

PMID- 27881569
TI  - Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose
      Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy
      (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration
      Betrixaban).
AB  - BACKGROUND: Stroke is a morbid and potentially mortal complication among patients
      hospitalized with acute medical illness. The potential of extended-duration
      thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of
      stroke compared with standard-dose enoxaparin in this population was assessed in
      this retrospective APEX trial substudy (Acute Medically Ill Venous
      Thromboembolism Prevention With Extended Duration Betrixaban). METHODS:
      Hospitalized acutely medically ill subjects (n=7513) were randomized in a double
      dummy double-blind fashion to either extended-duration oral betrixaban (80 mg
      once daily for 35-42 days) or standard-dose subcutaneous enoxaparin (40 mg once
      daily for 10+/-4 days) for venous thromboprophylaxis. Stroke events were
      adjudicated by an independent, blinded event adjudication committee. RESULTS: The
      mean age of study participants was 76 years; 45% were male; 13% had had a stroke;
      and 45% had congestive heart failure. There were fewer all-cause strokes (0.54%
      versus 0.97%; relative risk [RR]=0.56; 95% confidence interval, 0.32-0.96;
      P=0.032; adjusted RR=0.43%; number needed to treat=233) and ischemic strokes
      (0.48% versus 0.91%; RR=0.53; 95% confidence interval, 0.30-0.94; P=0.026;
      adjusted RR=0.43%; number needed to treat=233) among patients treated with
      betrixaban versus enoxaparin through 77 days of follow-up. Among high-risk
      subjects, those with congestive heart failure or ischemic stroke as their index
      event, betrixaban reduced the risk of all-cause stroke (0.72% versus 1.48%;
      RR=0.49; 95% confidence interval, 0.26-0.90; P=0.019; adjusted RR=0.76%; number
      needed to treat=132) and ischemic stroke (0.63% versus 1.38%; RR=0.45; 95%
      confidence interval, 0.24-0.87; P=0.014; adjusted RR=0.75%; number needed to
      treat=134) compared with enoxaparin. CONCLUSIONS: Among hospitalized medically
      ill patients, extended-duration betrixaban significantly reduced all-cause stroke
      and ischemic stroke through 77 days of follow-up CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT01583218.

PMID- 27881570
TI  - Excess Cardiovascular Risk in Women Relative to Men Referred for Coronary
      Angiography Is Associated With Severely Impaired Coronary Flow Reserve, Not
      Obstructive Disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) fatality rates are higher for women than
      for men, yet obstructive coronary artery disease (CAD) is less prevalent in
      women. Coronary flow reserve (CFR), an integrated measure of large- and small
      vessel CAD and myocardial ischemia, identifies patients at risk for CVD death,
      but is not routinely measured in clinical practice. We sought to investigate the
      impact of sex, CFR, and angiographic CAD severity on adverse cardiovascular
      events. METHODS: Consecutive patients (n=329, 43% women) referred for invasive
      coronary angiography after stress testing with myocardial perfusion positron
      emission tomography and with left ventricular ejection fraction >40% were
      followed (median, 3.0 years) for a composite end point of major adverse
      cardiovascular events, including cardiovascular death and hospitalization for
      nonfatal myocardial infarction or heart failure. The extent and severity of
      angiographic CAD were estimated by using the CAD prognostic index, and CFR was
      quantified by using positron emission tomography. RESULTS: Although women in
      comparison with men had lower pretest clinical scores, rates of prior myocardial
      infarction, and burden of angiographic CAD (P<0.001), they demonstrated greater
      risk of CVD events, even after adjustment for traditional risk factors, imaging
      findings, and early revascularization (adjusted hazard ratio, 2.05; 95%
      confidence interval, 1.05-4.02; P=0.03). Impaired CFR was similarly present among
      women and men, but in patients with low CFR (<1.6, n=163), women showed a higher
      frequency of nonobstructive CAD, whereas men showed a higher frequency of
      severely obstructive CAD (P=0.002). After also adjusting for CFR, the effect of
      sex on outcomes was no longer significant. When stratified by sex and CFR, only
      women with severely impaired CFR demonstrated significantly increased adjusted
      risk of CVD events (P<0.0001, P for interaction=0.04). CONCLUSIONS: Women
      referred for coronary angiography had a significantly lower burden of obstructive
      CAD in comparison with men but were not protected from CVD events. Excess
      cardiovascular risk in women was independently associated with impaired CFR,
      representing a hidden biological risk, and a phenotype less amenable to
      revascularization. Impaired CFR, particularly absent severely obstructive CAD,
      may represent a novel target for CVD risk reduction.

PMID- 27881574
TI  - Global health, human rights and the challenge of neoliberal policies.

PMID- 27881575
TI  - INTEGRATE-HTA: adopting and implementing an integrated perspective on complex
      interventions.

PMID- 27881573
TI  - Intestinal Na+, K+, 2Cl- cotransporter 2 plays a crucial role in hyperosmotic
      transitions of a euryhaline teleost.
AB  - Euryhaline fishes, such as the red drum (Sciaenops ocellatus), must quickly
      transition between hyperosmotic and hypoosmotic physiological strategies. When
      freshwater individuals transition to seawater they are exposed to increased
      diffusive water loss and ion gain. To maintain osmoregulatory balance these
      animals must drink and absorb seawater through the intestine, followed by ion
      excretion at the gills. The ability of fishes to transition between strategies
      can limit the magnitude of osmotic shock that can be tolerated. Here, we
      demonstrate that red drum can tolerate direct transfer from freshwater to full
      strength seawater with marginal impacts on osmotic balance, as indicated by
      plasma and muscle ion concentration, as well as muscle water. Seawater transition
      is concurrent with a significant increase in intestinal fluid volume. Typical
      patterns of osmoregulatory plasticity were observed in the gill with increased
      expression of nkcc1 and cftr Expression changes in the anterior intestine were
      observed after 24 h for nkcc2 with smaller and later responses observed for
      slc26a3, slc26a6, and nbc Immunofluorescence staining demonstrated similar
      patterns of NKCC localization in freshwater and seawater intestines; however,
      reduced basolateral staining of V-type ATPase was observed in seawater.
      Electrophysiological preparations demonstrated that seawater fish had increased
      absorptive current in the anterior intestine, which was significantly reduced in
      the presence of 10 MUmol/L bumetanide. Overall, these results suggest that nkcc2
      plays a crucial role during hyperosmotic transitions, and may be a more important
      complement to the well-known bicarbonate secretion pathway than generally
      considered.

PMID- 27881576
TI  - Exploring men's perceptions of a community-based men's shed programme in England.
AB  - Background: Sheds have been used in Australia for decades as an intervention to
      try and promote 'health by stealth' among men by providing a social space for
      those who may be particularly vulnerable to poor mental health. Little is known
      about the impact of men's sheds in England. Methods: Members of 19 sheds from one
      local authority area were invited to participate in focus groups to explore their
      perceptions of their shed. In total, 32 men participated in five focus groups
      which were analysed using applied thematic analysis. Results: While some sheds
      run activities, the main driving factor of sheds was the social aspect, with many
      coming along for nothing more than a chat and a cup of tea, allowing men to
      recapture lost social networks from their working days. However, it was felt that
      there could be more formal links forged between individual groups, which may
      result in a better range of activities on offer. Conclusions: This study
      indicates that the shed can be an effective way of reducing social isolation in
      older men. However, further work is needed to understand what impact the shed has
      on physical and mental well-being.

PMID- 27881572
TI  - The roles of the Na+/K+-ATPase, NKCC, and K+ channels in regulating local
      sweating and cutaneous blood flow during exercise in humans in vivo.
AB  - Na+/K+-ATPase has been shown to regulate the sweating and cutaneous vascular
      responses during exercise; however, similar studies have not been conducted to
      assess the roles of the Na-K-2Cl co-transporter (NKCC) and K+ channels.
      Additionally, it remains to be determined if these mechanisms underpinning the
      heat loss responses differ with exercise intensity. Eleven young (24 +/- 4 years)
      males performed three 30-min semirecumbent cycling bouts at low (30% VO2peak),
      moderate (50% VO2peak), and high (70% VO2peak) intensity, respectively, each
      separated by 20-min recovery periods. Using intradermal microdialysis, four
      forearm skin sites were continuously perfused with either: (1) lactated Ringer
      solution (Control); (2) 6 mmol.L-1 ouabain (Na+/K+-ATPase inhibitor); (3) 10
      mmol.L-1 bumetanide (NKCC inhibitor); or (4) 50 mmol.L-1 BaCl2 (nonspecific K+
      channel inhibitor); sites at which we assessed local sweat rate (LSR) and
      cutaneous vascular conductance (CVC). Inhibition of Na+/K+-ATPase attenuated LSR
      compared to Control during the moderate and high-intensity exercise bouts (both P
      ? 0.01), whereas attenuations with NKCC and K+ channel inhibition were only
      apparent during the high-intensity exercise bout (both P <= 0.05). Na+/K+-ATPase
      inhibition augmented CVC during all exercise intensities (all P ? 0.01), whereas
      CVC was greater with NKCC inhibition during the low-intensity exercise only (P ?
      0.01) and attenuated with K+ channel inhibition during the moderate and high
      intensity exercise conditions (both P ? 0.01). We show that Na+/K+-ATPase, NKCC
      and K+ channels all contribute to the regulation of sweating and cutaneous blood
      flow but their influence is dependent on the intensity of dynamic exercise.

PMID- 27881577
TI  - The design and psychometric assessment of a child-friendly TPB-based
      questionnaire.
AB  - Background: Despite the popularity of the theory of planned behaviour (TPB), a
      lack of research assessing the efficacy of the model in understanding the health
      behaviour of children exists. The aim of this study was to develop and test a TPB
      based measure suitable for use with schoolchildren aged 9-10 years. Methods: A
      mixed-method sequential design was employed. In Phase 1, semi-structured focus
      group discussions were conducted to elicit the underlying beliefs specific to
      tooth brushing. Using content thematic analysis, the beliefs were identified and
      a TPB measure was developed. A repeated measures design was employed in Phase 2
      using test-retest reliability analysis in order to assess its psychometric
      properties. In all, 184 children completed the questionnaire. Results: The
      questionnaire proved to be reliable for assessing the tooth brushing beliefs of
      children. Pearson's product moment correlations were calculated for all of the
      TPB constructs, achieving substantial to almost perfect agreement levels,
      providing strong predictive power of the TPB. Conclusions: The design and
      development of the measure are described, which could serve as a guide to fellow
      researchers and health professionals interested in using theoretical models to
      investigate the health and well-being of children.

PMID- 27881579
TI  - An miRNA-DNMT1 Axis Is Involved in Azacitidine Resistance and Predicts Survival
      in Higher-Risk Myelodysplastic Syndrome and Low Blast Count Acute Myeloid
      Leukemia.
AB  - Purpose: Azacitidine inhibits DNA methyltransferases, including DNMT1, and is
      currently the standard of care for patients with higher-risk myelodysplastic
      syndrome (HRMDS) or low blast count acute myeloid leukemia (AML).Experimental
      Design: The expression of 754 miRNAs was compared in azacitidine-resistant and
      azacitidine-sensitive myelodysplastic syndrome cells. We investigated the role of
      differentially expressed miRNAs on DNMT1 expression and azacitidine resistance in
      vitro We next evaluated anti-DNMT1 miRNA expression in pretreatment bone marrow
      samples derived from 75 patients treated with azacitidine for HRMDS or
      AML.Results: Seven miRNAs, including 5 that in silico targeted the DNMT1 3' UTR,
      were repressed in azacitidine-resistant cells in which DNMT1 protein levels were
      significantly higher. Ectopic anti-DNMT1 miRNA expression decreased DNMT1
      expression and increased azacitidine sensitivity, whereas specific inhibition of
      endogenous anti-DNMT1 miRNAs increased DNMT1 expression and triggered azacitidine
      resistance. In patients treated with azacitidine, decreased expression of anti
      DNMT1 miRNAs was associated with poor outcome. miR-126* had the strongest
      prognostic impact. Patients with miR-126*low myelodysplastic syndrome had
      significantly lower response rates (P = 0.04) and higher relapse rates (P =
      0.03), as well as shorter progression-free (PFS; P = 0.004) and overall survival
      (OS; P = 0.004). Multivariate analysis showed that age, miR-126* expression, and
      revised International Prognostic Scoring System risk independently predicted PFS
      and OS. In 15 patient samples collected over time, decreased miRNA expression
      levels were associated with secondary resistance.Conclusions: A decreased
      expression of anti-DNMT1 miRNAs might account for azacitidine resistance in HRMDS
      and AML, and measuring miRNA expression before and during treatment might help
      predict primary or secondary azacitidine resistance. Clin Cancer Res; 23(12);
      3025-34. (c)2016 AACR.

PMID- 27881578
TI  - Cytoplasmic Cyclin E Predicts Recurrence in Patients with Breast Cancer.
AB  - Purpose: Low molecular weight cyclin E (LMW-E) detected by Western blot analysis
      predicts for reduced breast cancer survival; however, it is impractical for
      clinical use. LMW-E lacks a nuclear localization signal that leads to
      accumulation in the cytoplasm that can be detected by IHC. We tested the
      hypothesis that cytoplasmic staining of cyclin E can be used as a predictor of
      poor outcome in different subtypes of breast cancer using patient cohorts with
      distinct clinical and pathologic features.Experimental Design: We evaluated the
      subcellular localization of cyclin E in breast cancer specimens from 2,494
      patients from 4 different cohorts: 303 from a prospective study and 2,191 from
      retrospective cohorts [NCI, MD Anderson Cancer Center (MDA), and the United
      Kingdom (UK)]. Median follow-up times were 8.0, 10.1, 13.5, and 5.7 years,
      respectively.Results: Subcellular localization of cyclin E on IHC was associated
      with full-length (nuclear) and low molecular weight isoforms (cytoplasmic) of
      cyclin E on Western blot analysis. In multivariable analysis, cytoplasmic cyclin
      E staining was associated with the greatest risk of recurrence compared with
      other prognostic factors across all subtypes in three (NCI, MDA, and UK) of the
      cohorts. In the MDA cohort, cytoplasmic cyclin E staining outperformed Ki67 and
      all other variables as prognostic factors.Conclusions: Cytoplasmic cyclin E
      identifies patients with the highest likelihood of recurrence consistently across
      different patient cohorts and subtypes. These patients may benefit from
      alternative therapies targeting the oncogenic isoforms of cyclin E. Clin Cancer
      Res; 23(12); 2991-3002. (c)2016 AACR.

PMID- 27881581
TI  - Nivolumab in the Treatment of Hodgkin Lymphoma.
AB  - Despite an extensive immune infiltrate that is recruited to the tumor by
      malignant Reed-Sternberg cells in Hodgkin lymphoma, the antitumor immune response
      is ineffective and unable to eradicate the malignant cells. The ineffective
      immune response is in part due to PD-1 signaling that renders intratumoral immune
      cells anergic. Reed-Sternberg cells have been shown to upregulate expression of
      the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at
      chromosome 9p24.1 or Epstein-Barr virus infection, and these ligands suppress the
      function of PD-1+ intratumoral T cells. Blockade of PD-1 signaling has proven to
      be a highly successful therapeutic approach, and the use of the anti-PD-1 mAb
      nivolumab recently received accelerated approval by the FDA for patients with
      classical Hodgkin lymphoma that has relapsed or progressed after autologous stem
      cell transplant and posttransplantation brentuximab vedotin. Initial clinical
      trials using nivolumab in this patient population resulted in high response rates
      that were durable. Adverse events associated with nivolumab included immune
      mediated adverse reactions and infusion reactions, but these were well tolerated,
      allowing for continued nivolumab administration. Clinical trials are now in
      progress to test the use of nivolumab in combination with standard chemotherapy
      or with novel agents with a goal of improving the outcome of patients with
      Hodgkin lymphoma. Clin Cancer Res; 23(7); 1623-6. (c)2016 AACR.

PMID- 27881580
TI  - Disruption of Autophagic Degradation with ROC-325 Antagonizes Renal Cell
      Carcinoma Pathogenesis.
AB  - Purpose: Although autophagy plays important roles in malignant pathogenesis and
      drug resistance, there are few clinical agents that disrupt this pathway, and the
      potential therapeutic benefit of autophagy inhibition remains undetermined. We
      used medicinal chemistry approaches to generate a series of novel agents that
      inhibit autophagic degradation.Experimental Design: ROC-325 was selected as a
      lead compound for further evaluation. Comprehensive in vitro and in vivo studies
      were conducted to evaluate the selectivity, tolerability, and efficacy of ROC-325
      in preclinical models of renal cell carcinoma (RCC) with HCQ serving as a
      comparator. Markers of autophagy inhibition and cell death were evaluated in
      tumor specimens.Results: ROC-325 exhibited superior in vitro anticancer effects
      compared with the existing autophagy inhibitor hydroxychloroquine (HCQ) in 12
      different cancer cell lines with diverse genetic backgrounds. Focused studies of
      the mechanism of action and efficacy of ROC-325 in RCC cells showed that drug
      treatment induced hallmark characteristics of autophagy inhibition, including
      accumulation of autophagosomes with undegraded cargo, lysosomal deacidification,
      p62 stabilization, and disruption of autophagic flux. Subsequent experiments
      showed that ROC-325 antagonized RCC growth and survival in an ATG5/7-dependent
      manner, induced apoptosis, and exhibited favorable selectivity. Oral
      administration of ROC-325 to mice bearing 786-0 RCC xenografts was well
      tolerated, was significantly more effective at inhibiting tumor progression than
      HCQ, and inhibited autophagy in vivoConclusions: Our findings demonstrate that
      ROC-325 has superior preclinical anticancer activity compared with HCQ and
      support the clinical investigation of its safety and preliminary efficacy in
      patients with RCC and other autophagy-dependent malignancies. Clin Cancer Res;
      23(11); 2869-79. (c)2016 AACR.

PMID- 27881583
TI  - Acute oesophageal necrosis in a young man with cocaine and alcohol abuse.
AB  - We report a case of acute oesophageal necrosis (AEN) and non-occlusive mesenteric
      ischaemia in an otherwise healthy 30-year-old man with cocaine and alcohol abuse.
      Although cocaine might be expected more frequently to cause oesophageal necrosis
      through sympathomimetic vasoconstriction, this is only the second known case
      report of AEN in a patient with cocaine abuse. His symptoms at presentation
      included epigastric abdominal pain, haematemesis and generalised weakness. He
      developed moderate neutropenia and severe lactic acidosis. Treatment consisted of
      intravenous proton-pump inhibitors, granulocyte colony stimulating factor, broad
      spectrum antibiotics and ultimately exploratory laparotomy after his condition
      worsened. He died within 24 hours of presentation from a combination of systemic
      inflammatory response syndrome, acute respiratory distress syndrome and
      disseminated intravascular coagulation. AEN was discovered postmortem. We
      conclude that AEN should be suspected in any patient with haematemesis and
      substance abuse, and discovery of AEN should prompt a thorough evaluation for
      potentially lethal comorbid conditions.

PMID- 27881584
TI  - Tuberculosis presenting as a 'swollen calf'.
AB  - We report the case of an 83-year-old man who presented with swelling of his left
      lower leg. Subsequent investigations revealed that the swelling was due to a
      Mycobacterium tuberculosis abscess in the tibialis anterior muscle.

PMID- 27881585
TI  - Partial interhemispheric disconnection syndrome (P-IHDS) secondary to Marchiafava
      Bignami disease type B (MBD-B).
AB  - A 53-year-old man with a 35-year history of excessive alcohol intake presents to
      our neurology department with 4-year history of progressive neurocognitive
      deterioration and disconnection syndrome. MRI head demonstrates extensive
      demyelination of the corpus callosum (and of extracallosal sites as well),
      leading to a diagnosis of Marchiafava-Bignami disease. He was given treatment
      with vitamin B complex (including folate) and was assessed and managed by
      psychology, occupational therapy and physiotherapy with initial signs of
      improvement.

PMID- 27881582
TI  - The Expanding Role of the BCL6 Oncoprotein as a Cancer Therapeutic Target.
AB  - BCL6 was initially discovered as an oncogene in B-cell lymphomas, where it drives
      the malignant phenotype by repressing proliferation and DNA damage checkpoints
      and blocking B-cell terminal differentiation. BCL6 mediates its effects by
      binding to hundreds of target genes and then repressing these genes by recruiting
      several different chromatin-modifying corepressor complexes. Structural
      characterization of BCL6-corepressor complexes suggested that BCL6 might be a
      druggable target. Accordingly, a number of compounds have been designed to bind
      to BCL6 and block corepressor recruitment. These compounds, based on peptide or
      small-molecule scaffolds, can potently block BCL6 repression of target genes and
      kill lymphoma cells. In the case of diffuse large B-cell lymphomas (DLBCL), BCL6
      inhibitors are equally effective in suppressing both the germinal center B-cell
      (GCB)- and the more aggressive activated B-cell (ABC)-DLBCL subtypes, both of
      which require BCL6 to maintain their survival. In addition, BCL6 is implicated in
      an expanding scope of hematologic and solid tumors. These include, but are not
      limited to, B-acute lymphoblastic leukemia, chronic myeloid leukemia, breast
      cancer, and non-small cell lung cancer. BCL6 inhibitors have been shown to exert
      potent effects against these tumor types. Moreover, mechanism-based combinations
      of BCL6 inhibitors with other agents have yielded synergistic and often quite
      dramatic activity. Hence, there is a compelling case to accelerate the
      development of BCL6-targeted therapies for translation to the clinical setting.
      Clin Cancer Res; 23(4); 885-93. (c)2016 AACR.

PMID- 27881586
TI  - Iatrogenic parafoveal macular hole following Nd-YAG posterior hyaloidotomy for
      premacular haemorrhage.
AB  - Premacular sub-internal limiting membrane (sub-ILM) haemorrhage is a known cause
      of sudden profound loss of vision. Neodymium-doped yttrium aluminium garnet (ND
      YAG) posterior hyaloidotomy is an inexpensive, effective and safe treatment
      modality for rapid drainage of haemorrhage covering the macula. An 18-year-old
      male patient presented to us with a history of Nd-YAG posterior hyaloidotomy for
      Valsalva-related premacular bleed. At the posterior pole, a cavity formed by the
      detached ILM with a central defect in ILM-posterior hyaloid complex was evident.
      High-definition optical coherence tomography (HD-OCT) showed normal foveal
      contour with a parafoveal macular hole. Hence, good clinical judgement,
      appropriate positioning of hyaloidotomy and use of lowest possible energy level
      is the key to a successful and safe laser drainage of a premacular haemorrhage.

PMID- 27881587
TI  - PAI-1 polymorphism as a cause of severe high altitude associated arteriovenous
      thrombosis.
AB  - We present a 34-year-old man who developed disseminated intra-arterial and venous
      thrombosis following exposure to extreme high altitude. On evaluation, the
      patient was found to have thrombosis involving the aorta, bilateral iliac
      arteries and middle cerebral artery. On detailed evaluation for the cause of
      recurrent seizures, he was also found to have cerebral venous thrombosis of the
      superior sagittal sinus. The patient underwent amputation of 3 limbs due to
      gangrene. Procoagulant work up revealed increased plasminogen activator inhibitor
      1 activity with 4G/4G polymorphism. This case highlights the life-threatening and
      limb-threatening thrombosis secondary to a rare inherited thrombophilia on
      exposure to extreme high altitude.

PMID- 27881588
TI  - Glucocorticoids did not reverse type 1 diabetes mellitus secondary to
      pembrolizumab in a patient with metastatic melanoma.
AB  - Immune checkpoint inhibitors offer patients with advanced melanoma substantial
      improvements in survival. Unlike chemotherapy, immune checkpoint inhibitors such
      as ipilimumab and pembrolizumab cause unique immune-related adverse events
      (irAEs), including the development of endocrinopathies. We report a case of a man
      aged 60 years who developed diabetic ketoacidosis (DKA) following the use of
      pembrolizumab for the treatment of metastatic melanoma. He received four cycles
      of ipilimumab, before proceeding to pembrolizumab. Five weeks after initiating
      pembrolizumab, he presented in DKA with a pH of 7.0, bicarbonate of 7 mmol/L,
      blood glucose of 27 mmol/L and serum ketones of 5.9 mmol/L. Antibodies to
      glutamic acid decarboxylase (anti-GAD) and Islet antigen 2 (IA-2) were negative
      and C-peptide was low at 57 pmol/L (300-2350 pmol/L). There was no personal or
      family history of autoimmune conditions. Standard immunosuppression for irAEs was
      started using prednisolone in an attempt to salvage beta cell function but was
      unsuccessful. To the best of our knowledge, this is the first reported attempt at
      reversing pembrolizumab-induced type 1 diabetes using glucocorticoids.

PMID- 27881590
TI  - Pyopneumothorax secondary to Streptococcus milleri infection.
AB  - We report a case of a 46-year-old Malay woman with underlying hypothyroidism post
      thyroidectomy who presented with worsening breathlessness, orthopnoea, productive
      cough and left-sided pleuritic chest pain of 3 days duration. Chest X-ray on
      admission showed left-sided massive hydropneumothorax. Pleural tapping revealed
      empyema. A chest tube was inserted immediately. The culture of pleural fluid grew
      Streptococcus constellatus The patient was treated with antibiotics for a total
      of 6 weeks and underwent open thoracotomy and decortication during admission.
      Subsequently, her lung condition improved and there was no evidence of recurrence
      during follow-up.

PMID- 27881589
TI  - Metastatic melanoma after 23 years of primary ocular melanoma.
AB  - We describe a case of 52-year-old man who presented with an episode of tonic
      clonic seizures. He had right ocular melanoma 23 years ago with subsequent
      enucleation which was the standard treatment at that time. CT scans of the brain
      and of the thorax-abdomen-pelvis revealed widespread metastatic lesions in the
      brain, lung and liver. Further investigations including bronchoscopy with
      cytopathology uncovered that the metastatic disease was a recurrence of ocular
      melanoma. He received palliative radiotherapy and died 6 months later. Ocular
      melanoma is often associated with fulminant metastatic disease after a period of
      dormancy. Thus, despite successful treatment of the localised disease at initial
      presentation, an effort is needed for optimal long-term follow-up plan in order
      to improve survival in case of recurrence.

PMID- 27881591
TI  - Vernal keratoconjunctivitis: culmination of management using immunosuppression,
      surgical and prosthetic therapy over quarter century.
AB  - A 22-year-old male patient presented in 1988 with active vernal
      keratoconjunctivitis. He was treated with topical mast cell stabilisers and
      corticosteroids. Chronic inflammation despite topical treatment necessitated oral
      immunosuppressants. Active disease came under control with this; however, the
      patient gradually developed limbal stem cell deficiency. He underwent bilateral
      pannus resection with amniotic membrane transplantation that resulted in improved
      ocular surface. In 2007, patient was found to have significant bilateral
      posterior subcapsular cataracts and underwent bilateral cataract surgery with
      intraocular lens implantation with good visual outcome. In 2016, he was provided
      with scleral lens prosthetic device, which further improved vision. At last
      follow-up, more than 25 years after his initial visit, his visual acuity was
      20/25 in both eyes with a stable surface. With a comprehensive approach using
      immunosuppression, surgical therapy and scleral lens prosthetic device, chronic
      vernal keratoconjunctivitis can be well managed as illustrated in this case.

PMID- 27881592
TI  - The C-3alpha Epimer of 25-Hydroxycholecalciferol from Endogenous and Exogenous
      Sources Supports Normal Growth and Bone Mineral Density in Weanling Rats.
AB  - BACKGROUND: The C-3alpha epimer of 25-hydroxycholecalciferol [3-epi-25(OH)D3] is
      elevated in infants. OBJECTIVES: We tested whether increasing cholecalciferol
      intake results in a dose-response in plasma 3-epi-25(OH)D3 We also examined bone
      and mineral metabolism in response to 3-epi-25(OH)D3 treatment. METHODS: Sprague
      Dawley rats (4 wk old) were randomly assigned (n = 6/group of each sex) to AIN
      93G diets with cholecalciferol at 1 (control), 2, or 4 IU/g diet for objective 1
      and to diets with 3-epi-25(OH)D3 at 0.5 or 1 IU/g diet or 25
      hydroxycholecalciferol [25(OH)D3] at 0.5 IU/g diet for objective 2 for 8 wk.
      Measurements at weeks 0, 4, and 8 included body weight and length, plasma vitamin
      D metabolites, bone biomarkers, and bone mineral density determined by using dual
      energy X-ray absorptiometry. Lumbar vertebra 3 (L3) geometry and volumetric bone
      mineral density (vBMD) were measured using microcomputed tomography. Differences
      between groups were identified for males and females separately. RESULTS: Weight
      and food intake were not different between groups. Elevated plasma 3-epi-25(OH)D3
      was observed only in females in the 4 IU cholecalciferol/g diet group (mean +/-
      SD: 24.7 +/- 17.1 ng/mL), compared with the control group (5.3 +/- 1.4 ng/mL; P =
      0.001). By week 8, both male and female rats in the 3-epi-25(OH)D3 groups had
      >87% greater plasma 3-epi-25(OH)D3 concentrations relative to the 25(OH)D3
      reference group (P < 0.0001). At week 8 in males only, parathyroid hormone was
      significantly lower (P = 0.019) in both 3-epi-25(OH)D3 groups than in the
      25(OH)D3 group, and L3 total vBMD was higher (P = 0.004) in the 0.5 IU 3-epi
      25(OH)D3 group than in the 25(OH)D3 group. CONCLUSIONS: Endogenously generated 3
      epi-25(OH)D3 is more prominent in female than in male rats. Exogenous 3-epi
      25(OH)D3 was as effective as 25(OH)D3 in supporting bone mineral accretion in
      both sexes. It thus appears that 3-epi-25(OH)D3 has biological activity and
      should be further explored.

PMID- 27881595
TI  - Decisive Decisions on Production Compared with Market Strategies to Improve Diets
      in Rural Africa.

PMID- 27881593
TI  - Dairy Food Intake Is Associated with Reproductive Hormones and Sporadic
      Anovulation among Healthy Premenopausal Women.
AB  - BACKGROUND: Dairy food intake has been associated with infertility; however,
      little is known with regard to associations with reproductive hormones or
      anovulation. OBJECTIVE: We investigated whether intakes of dairy foods and
      specific nutrients were associated with reproductive hormone concentrations
      across the cycle and the risk of sporadic anovulation among healthy women.
      METHODS: We prospectively measured serum reproductive hormones <=8
      times/menstrual cycle for 2 cycles from 259 regularly menstruating women (mean
      age: 27.3 y). Dairy food intake was assessed via 24-h dietary recalls 4
      times/cycle. Dairy food intakes were assessed by 1) total and low- and high-fat
      dairy products; 2) dairy nutrients, including fat, lactose, calcium, and
      phosphorus; and 3) dairy foods, including milk, cheese, butter, cream, yogurt,
      and ice cream categories. Weighted linear mixed models were used to evaluate
      associations between dairy nutrients or food intakes and hormone concentrations.
      Modified Poisson regression models with robust error variance were used to
      evaluate anovulation. Models were adjusted for age, body mass index, race,
      physical activity, Mediterranean diet score, total energy, protein, fiber,
      caffeine, and other hormones. RESULTS: Each serving increase in total and low-
      and high-fat dairy foods and all increases in amounts of all dairy nutrients
      tested were associated with an ~5% reduction in serum estradiol concentrations
      but were not associated with anovulation. Total and high-fat dairy food intakes
      were positively associated with serum luteinizing hormone concentrations. We
      observed associations between intakes of >0 servings of yogurt (RR: 2.1; 95% CI:
      1.2, 3.7) and cream (RR: 1.8; 95% CI: 1.0, 3.2) and a higher risk of sporadic
      anovulation compared with no intake. CONCLUSIONS: Our study showed associations
      between increasing dairy food and nutrient intakes and decreasing estradiol
      concentrations as well as between cream and yogurt intakes and the risk of
      sporadic anovulation. These results highlight the potential role of dairy in
      reproductive function in healthy women.

PMID- 27881594
TI  - Hepatic Activity and Transcription of Betaine-Homocysteine Methyltransferase,
      Methionine Synthase, and Cystathionine Synthase in Periparturient Dairy Cows Are
      Altered to Different Extents by Supply of Methionine and Choline.
AB  - BACKGROUND: Compared with choline, Met enhances milk yield and feed intake, and
      elicits a better immuno-metabolic status in periparturient cows. It is unknown
      whether hepatic activity and transcription of betaine-homocysteine
      methyltransferase (BHMT), 5-methyltetrahydrofolate-homocysteine methyltransferase
      (MTR), and cystathionine beta-synthase (CBS) are responsive to Met and choline
      supply. OBJECTIVE: This study sought to characterize hepatic BHMT, MTR, and CBS
      transcription and activity in response to Met and choline supplementation.
      METHODS: Forty multiparous cows were used in a 2 * 2 factorial design from -21 d
      through 30 d around parturition to assess effects of dietary rumen-protected Met
      (0% or 0.08% dry matter basis) or rumen-protected choline (0 or 60 g . cow-1 . d
      1). Liver tissue obtained on days -10, 7, 20, and 30 was used for analyses.
      RESULTS: Met-supplemented cows had greater methionine adenosyltransferase 1A
      (MAT1A) (0.38 compared with 0.27; SEM = 0.05; P = 0.02) and
      phosphatidylethanolamine methyltransferase (PEMT) (0.74 compared with 0.58; SEM =
      0.08; P = 0.05) expression. Greater S-adenosylhomocysteine hydrolase (SAHH) (0.93
      compared with 0.74; SEM = 0.05; P = 0.01) and CBS (1.16 compared with 1.02; SEM =
      0.07; P = 0.04), as well as lower MTR activity (23.4 compared with 29.7 nmol
      product . h-1 . mg protein-1; SEM = 2.9; P = 0.04), also were detected in Met-
      but not choline-supplemented cows. Although BHMT and MTR expression and BHMT
      enzyme activity did not change (P > 0.05), MTR enzyme activity was lower in
      choline-supplemented cows (23.5 compared with 29.6 nmol product . h-1 . mg
      protein-1; SEM = 2.9; P = 0.05). CONCLUSIONS: These findings indicate that
      greater synthesis of phosphatidylcholine and antioxidants contribute to the
      better performance and immuno-metabolic status in Met-supplemented cows. Failure
      to generate a comparable amount of endogenous Met from choline could be one
      reason that choline-fed cows fail to achieve comparable performance and health
      benefits during the periparturient period.

PMID- 27881596
TI  - Combined Iron Deficiency and Low Aerobic Fitness Doubly Burden Academic
      Performance among Women Attending University.
AB  - BACKGROUND: Academic success is a key determinant of future prospects for
      students. Cognitive functioning has been related to nutritional and physical
      factors. Here, we focus on iron status and aerobic fitness in young-adult female
      students given the high rate of iron deficiency and declines in fitness reported
      in this population. OBJECTIVES: We sought to explore the combined effects of iron
      status and fitness on academic success and to determine whether these
      associations are mediated by cognitive performance. METHODS: Women (n = 105) aged
      18-35 y were recruited for this cross-sectional study. Data were obtained for
      iron biomarkers, peak oxygen uptake (VO2peak), grade point average (GPA),
      performance on computerized attention and memory tasks, and motivation and
      parental occupation. We compared the GPA of groups 1) with low compared with
      normal iron status, 2) among different fitness levels, and 3) by using a combined
      iron status and fitness designation. Mediation analysis was applied to determine
      whether iron status and VO2peak influence GPA through attentional and mnemonic
      function. RESULTS: After controlling for age, parental occupation, and
      motivation, GPA was higher in women with normal compared with low ferritin (3.66
      +/- 0.06 compared with 3.39 +/- 0.06; P = 0.01). In analyses of combined effects
      of iron status and fitness, GPA was higher in women with normal ferritin and
      higher fitness (3.70 +/- 0.08) than in those with 1) low ferritin and lower
      fitness (3.36 +/- 0.08; P = 0.02) and 2) low ferritin and higher fitness (3.44 +/
      0.09; P = 0.04). Path analysis revealed that working memory mediated the
      association between VO2peak and GPA. CONCLUSIONS: Low iron stores and low aerobic
      fitness may prevent female college students from achieving their full academic
      potential. Investigators should explore whether integrated lifestyle
      interventions targeting nutritional status and fitness can benefit cognitive
      function, academic success, and postgraduate prospects.

PMID- 27881597
TI  - Assessment of Regression Models for Adjustment of Iron Status Biomarkers for
      Inflammation in Children with Moderate Acute Malnutrition in Burkina Faso.
AB  - BACKGROUND: Biomarkers of iron status are affected by inflammation. In order to
      interpret them in individuals with inflammation, the use of correction factors
      (CFs) has been proposed. OBJECTIVE: The objective of this study was to
      investigate the use of regression models as an alternative to the CF approach.
      METHODS: Morbidity data were collected during clinical examinations with
      morbidity recalls in a cross-sectional study in children aged 6-23 mo with
      moderate acute malnutrition. C-reactive protein (CRP), alpha1-acid glycoprotein
      (AGP), serum ferritin (SF), and soluble transferrin receptor (sTfR) were measured
      in serum. Generalized additive, quadratic, and linear models were used to model
      the relation between SF and sTfR as outcomes and CRP and AGP as categorical
      variables (model 1; equivalent to the CF approach), CRP and AGP as continuous
      variables (model 2), or CRP and AGP as continuous variables and morbidity
      covariates (model 3) as predictors. The predictive performance of the models was
      compared with the use of 10-fold crossvalidation and quantified with the use of
      root mean square errors (RMSEs). SF and sTfR were adjusted with the use of
      regression coefficients from linear models. RESULTS: Crossvalidation revealed no
      advantage to using generalized additive or quadratic models over linear models in
      terms of the RMSE. Linear model 3 performed better than models 2 and 1.
      Furthermore, we found no difference in CFs for adjusting SF and those from a
      previous meta-analysis. Adjustment of SF and sTfR with the use of the best
      performing model led to a 17% point increase and <1% point decrease,
      respectively, in estimated prevalence of iron deficiency. CONCLUSION: Regression
      analysis is an alternative to adjust SF and may be preferable in research
      settings, because it can take morbidity and severity of inflammation into
      account. In clinical settings, the CF approach may be more practical. There is no
      benefit from adjusting sTfR. This trial was registered at www.controlled
      trials.com as ISRCTN42569496.

PMID- 27881598
TI  - The right pick: structural basis of snRNA selection by Gemin5.
AB  - Macromolecular complexes, rather than individual biopolymers, perform many
      cellular activities. Faithful assembly of these complexes in vivo is therefore a
      vital challenge of all cells, and its failure can have fatal consequences. To
      form functional complexes, cells use elaborate measures to select the "right"
      components and combine them into working entities. How assembly is achieved at
      the molecular level is unclear in many cases. Three groups (Jin and colleagues,
      pp. 2391-2403; Xu and colleagues, pp. 2376-2390; and Tang and colleagues in Cell
      Research) have now provided insights into how an assembly factor specifically
      recognizes substrate RNA molecules and enables their usage for assembly of Sm
      class uridine-rich small nuclear RNA-protein complexes.

PMID- 27881600
TI  - Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP
      assembly.
AB  - In cytoplasm, the survival of motor neuron (SMN) complex delivers pre-small
      nuclear RNAs (pre-snRNAs) to the heptameric Sm ring for the assembly of the ring
      complex on pre-snRNAs at the conserved Sm site [A(U)4-6G]. Gemin5, a WD40 protein
      component of the SMN complex, is responsible for recognizing pre-snRNAs. In
      addition, Gemin5 has been reported to specifically bind to the m7G cap. In this
      study, we show that the WD40 domain of Gemin5 is both necessary and sufficient
      for binding the Sm site of pre-snRNAs by isothermal titration calorimetry (ITC)
      and mutagenesis assays. We further determined the crystal structures of the WD40
      domain of Gemin5 in complex with the Sm site or m7G cap of pre-snRNA, which
      reveal that the WD40 domain of Gemin5 recognizes the Sm site and m7G cap of pre
      snRNAs via two distinct binding sites by respective base-specific interactions.
      In addition, we also uncovered a novel role of Gemin5 in escorting the truncated
      forms of U1 pre-snRNAs for proper disposal. Overall, the elucidated Gemin5
      structures will contribute to a better understanding of Gemin5 in small nuclear
      ribonucleic protein (snRNP) biogenesis as well as, potentially, other cellular
      activities.

PMID- 27881601
TI  - Structural basis for snRNA recognition by the double-WD40 repeat domain of
      Gemin5.
AB  - Assembly of the spliceosomal small nuclear ribonucleoparticle (snRNP) core
      requires the participation of the multisubunit SMN (survival of motor neuron)
      complex, which contains SMN and several Gemin proteins. The SMN and Gemin2
      subunits directly bind Sm proteins, and Gemin5 is required for snRNP biogenesis
      and has been implicated in snRNA recognition. The RNA sequence required for snRNP
      assembly includes the Sm site and an adjacent 3' stem-loop, but a precise
      understanding of Gemin5's RNA-binding specificity is lacking. Here we show that
      the N-terminal half of Gemin5, which is composed of two juxtaposed seven-bladed
      WD40 repeat domains, recognizes the Sm site. The tandem WD40 repeat domains are
      rigidly held together to form a contiguous RNA-binding surface. RNA-contacting
      residues are located mostly on loops between beta strands on the apical surface
      of the WD40 domains. Structural and biochemical analyses show that base-stacking
      interactions involving four aromatic residues and hydrogen bonding by a pair of
      arginines are crucial for specific recognition of the Sm sequence. We also show
      that an adenine immediately 5' to the Sm site is required for efficient binding
      and that Gemin5 can bind short RNA oligos in an alternative mode. Our results
      provide mechanistic understandings of Gemin5's snRNA-binding specificity as well
      as valuable insights into the molecular mechanism of RNA binding by WD40 repeat
      proteins in general.

PMID- 27881603
TI  - A protective role of IL-37 in cancer: a new hope for cancer patients.
AB  - IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico
      in 2000, significant advances in the understanding of its biology were made only
      in recent years. It is a member of the family with potent anti-inflammatory and
      immunosuppressive properties. It is produced as a precursor without a classic
      signal peptide. The precursor is cleaved into mature form in the cytoplasm by
      caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to
      the nucleus, and suppresses transcription of several proinflammatory genes. Both
      precursor and cleaved forms of IL-37 are secreted. They bind IL-18Ralpha chain
      (also used by IL-18 as a receptor subunit) and recruit Toll/IL-1R (TIR)-8 for
      transducing intracellular signaling. TIR-8 is a member of the IL-1 receptor
      family (IL-1RF) and was previously known as an orphan receptor. IL-37 suppresses
      activation of NF-kappaB and MAPK and activates Mer-PTEN-DOK pathway. It
      negatively regulates signaling mediated by TLR agonists, proinflammatory
      cytokines, and IL-1RF ligands. It also affects cell metabolism by inhibiting
      mTOR, GSK-3alpha/beta, and activating AMPK. Despite having the ability to dampen
      host's immune responses, the cytokine has been shown to exert antitumor effects,
      and it has been suggested that it may act as a prognostic marker in a variety of
      human cancers. Recent studies have suggested that IL-37 may represent a novel
      therapeutic tool in patients with cancer. In this review, we provide an overview
      of the cytokine biology, discuss recent advances made in unraveling its anti
      cancer effects, and suggest guidelines for future research.

PMID- 27881599
TI  - Undercover: gene control by metabolites and metabolic enzymes.
AB  - To make the appropriate developmental decisions or maintain homeostasis, cells
      and organisms must coordinate the expression of their genome and metabolic state.
      However, the molecular mechanisms that relay environmental cues such as nutrient
      availability to the appropriate gene expression response remain poorly
      understood. There is a growing awareness that central components of intermediary
      metabolism are cofactors or cosubstrates of chromatin-modifying enzymes. As such,
      their concentrations constitute a potential regulatory interface between the
      metabolic and chromatin states. In addition, there is increasing evidence for a
      direct involvement of classic metabolic enzymes in gene expression control. These
      dual-function proteins may provide a direct link between metabolic programing and
      the control of gene expression. Here, we discuss our current understanding of the
      molecular mechanisms connecting metabolism to gene expression and their
      implications for development and disease.

PMID- 27881602
TI  - N-terminal acetylation promotes synaptonemal complex assembly in C. elegans.
AB  - N-terminal acetylation of the first two amino acids on proteins is a prevalent
      cotranslational modification. Despite its abundance, the biological processes
      associated with this modification are not well understood. Here, we mapped the
      pattern of protein N-terminal acetylation in Caenorhabditis elegans, uncovering a
      conserved set of rules for this protein modification and identifying substrates
      for the N-terminal acetyltransferase B (NatB) complex. We observed an enrichment
      for global protein N-terminal acetylation and also specifically for NatB
      substrates in the nucleus, supporting the importance of this modification for
      regulating biological functions within this cellular compartment. Peptide
      profiling analysis provides evidence of cross-talk between N-terminal acetylation
      and internal modifications in a NAT substrate-specific manner. In vivo studies
      indicate that N-terminal acetylation is critical for meiosis, as it regulates the
      assembly of the synaptonemal complex (SC), a proteinaceous structure ubiquitously
      present during meiosis from yeast to humans. Specifically, N-terminal acetylation
      of NatB substrate SYP-1, an SC structural component, is critical for SC assembly.
      These findings provide novel insights into the biological functions of N-terminal
      acetylation and its essential role during meiosis.

PMID- 27881604
TI  - CD11d beta2 integrin expression on human NK, B, and gammadelta T cells.
AB  - The CD11d integrin is expressed on the cell surface of leukocytes that belong to
      the myeloid lineage, but its expression on lymphocytes remains unexplored. To
      test the hypothesis that CD11d is expressed on lymphocyte subsets, we employed a
      multicolor flow cytometry panel to identify CD11d expression on B, NK, CD4+ and
      CD8+ alphabeta T cells (alphabetaTc), and gammadelta T cells (gammadeltaTc) in
      human PBMC samples. CD11d was highly expressed on NK cells, B cells, and
      gammadeltaTc, but not alphabetaTc. CD11d expression was higher on freshly
      isolated gammadeltaTc compared with alphabetaTc from healthy donors, yet both
      inter- and intradonor variability was evident. Over time in primary culture, we
      consistently observed higher CD11d levels on gammadeltaTc compared with
      alphabetaTc from the same donor. Furthermore, CD11d expression on gammadeltaTc
      increased over time and correlated with levels of IL-2 supplementation. Of
      interest, a greater percentage of Vdelta1 gammadeltaTc expressed CD11d than did
      Vdelta2 gammadeltaTc, which suggested differential roles for this integrin that
      may segregate with gammadeltaTc subsets. These results expand the potential for
      CD11d to regulate lymphocyte migration and tissue retention, and illuminate the
      possibility of a previously unconsidered role for CD11d in leukocyte biology and
      disease.

PMID- 27881605
TI  - Monocytes and dendritic cells are the primary sources of interleukin 37 in human
      immune cells.
AB  - The interleukin (IL)-1 family member IL-37 is one of few anti-inflammatory
      cytokines, and it is capable of countering a broad spectrum of proinflammatory
      assaults. Although it is known that leukocytes are a major source of IL-37,
      knowledge on IL-37 production and secretion in specific immune cell types remains
      limited. Thus, we investigated IL-37 mRNA expression as well as protein
      production and secretion in human PBMCs. In PBMCs stimulated with agonists of
      Toll-like receptors (TLRs) 1-6 and 9, IL1F7 (the IL-37-encoding gene) was induced
      up to 9-fold, peaked at 6-8 h and returned to steady-state at 72 h. LPS-induced
      IL1F7 expression comprised isoforms b and c but not a and e Flow cytometry
      revealed that among IL-37+ PBMCs, monocytes predominated (81-91%), but T cells (6
      8%) and myeloid dendritic cells (mDCs, 1-2%) also contributed to the IL-37+
      leukocyte pool. Monocytes and mDCs, but not T cells, were capable of secreting IL
      37. Whereas monocytes and mDCs secreted IL-37 upon LPS stimulation, only mDCs
      also released IL-37 at steady-state. Among monocyte subsets, IL-37 was LPS
      inducible and secreted only in classical and, although less pronounced, in
      intermediate monocytes; secretion was observed as early as 3 h after stimulation.
      Overall, our data suggest that constitutive IL-37 secretion by mDCs may serve to
      maintain an anti-inflammatory milieu at steady state, whereas IL-37 is stored in
      monocytes to be available for rapid release upon inflammatory encounters, thus
      acting as a novel anti-inflammatory alarmin. These insights may prove important
      to advancing towards clinical use the protective functions of one of the most
      powerful anti-inflammatory mediators so far discovered.

PMID- 27881606
TI  - Mitochondria Protection after Acute Ischemia Prevents Prolonged Upregulation of
      IL-1beta and IL-18 and Arrests CKD.
AB  - The innate immune system has been implicated in both AKI and CKD. Damaged
      mitochondria release danger molecules, such as reactive oxygen species, DNA, and
      cardiolipin, which can cause NLRP3 inflammasome activation and upregulation of IL
      18 and IL-1beta It is not known if mitochondrial damage persists long after
      ischemia to sustain chronic inflammasome activation. We conducted a 9-month study
      in Sprague-Dawley rats after 45 minutes of bilateral renal ischemia. We detected
      glomerular and peritubular capillary rarefaction, macrophage infiltration, and
      fibrosis at 1 month. Transmission electron microscopy revealed mitochondrial
      degeneration, mitophagy, and deformed foot processes in podocytes. These changes
      progressed over the study period, with a persistent increase in renal cortical
      expression of IL-18, IL-1beta, and TGF-beta, despite a gradual decline in TNF
      alpha expression and macrophage infiltration. Treatment with a mitoprotective
      agent (SS-31; elamipretide) for 6 weeks, starting 1 month after ischemia,
      preserved mitochondrial integrity, ameliorated expression levels of all
      inflammatory markers, restored glomerular capillaries and podocyte structure, and
      arrested glomerulosclerosis and interstitial fibrosis. Further, helium ion
      microscopy vividly demonstrated the restoration of podocyte structure by SS-31.
      The protection by SS-31 was sustained for >=6 months after treatment ended, with
      normalization of IL-18 and IL-1beta expression. These results support a role for
      mitochondrial damage in inflammasome activation and CKD and suggest mitochondrial
      protection as a novel therapeutic approach that can arrest the progression of
      CKD. Notably, SS-31 is effective when given long after AKI and provides
      persistent protection after termination of drug treatment.

PMID- 27881608
TI  - Genetics of Diabetic Kidney Disease-From the Worst of Nightmares to the Light of
      Dawn?

PMID- 27881609
TI  - Epstein-Barr Virus in Nasopharyngeal Carcinoma of Guatemalan and Brazilian
      Patients.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr
      virus (EBV), particularly the undifferentiated nonkeratinizing subtype.
      Prevalence of EBV in NPC in countries such as Guatemala and Brazil has not been
      studied. METHODS: We analyzed 19 cases of NPC, 11 from Guatemala and 8 from
      Brazil, for the presence of EBV by in situ hybridization and
      immunohistochemistry. Additionally, 19 hyperplastic adenoids from children were
      analyzed for EBV by in situ hybridization, 12 from Guatemala and 7 from Brazil.
      RESULTS: All the NPC cases from Guatemala and 5 from Brazil were of the
      undifferentiated nonkeratinizing type. EBV-negative cases comprised 2
      keratinizing NPC and 1 differentiated nonkeratinizing NPC. All undifferentiated
      nonkeratinizing NPC from both samples showed intense positivity for EBER, while
      LMP-1 only focally and scarcely expressed. EBER was positive in 75% and 43% of
      the adenoids from Guatemala and Brazil, respectively. CONCLUSIONS: All
      undifferentiated nonkeratinizing NPC irrespective of origin from Guatemala or
      Brazil were highly associated with EBV.

PMID- 27881610
TI  - Primary Leiomyosarcoma of the Ovarian Vein: Case Report and Literature Review.
AB  - Primary leiomyosarcoma arising from the ovarian vein is extremely rare, with only
      10 cases reported in the literature. We report on a case of leiomyosarcoma of the
      left ovarian vein in a 67-year-old woman who presented with abdominal discomfort.
      Pelvic ultrasound revealed a large, solid, irregular mass in close relation to
      the left ovary. The patient subsequently underwent a total hysterectomy with
      bilateral salpingo-oophorectomy. Histologically, the tumor was composed of
      interlacing fascicles of spindle cells with abundant eosinophilic cytoplasm,
      hyperchromatic nuclei, and prominent nucleoli. Mitotic activity was high, with 24
      mitoses in 10 high-power fields. Areas of necrosis and hemorrhage were present
      within the tumor. Immunohistochemically, the tumor cells showed diffuse
      immunoreactivity for vimentin, muscle-specific actin, desmin, and caldesmon. The
      patient received chemotherapy postoperatively but subsequently developed
      disseminated metastatic disease (lung, liver, iliac lymph nodes, and peritoneum).
      Primary leiomyosarcomas arising from the ovarian vein are aggressive neoplasms,
      and the prognosis correlates with stage.

PMID- 27881607
TI  - Bicarbonate Balance and Prescription in ESRD.
AB  - The optimal approach to managing acid-base balance is less well defined for
      patients receiving hemodialysis than for those receiving peritoneal dialysis.
      Interventional studies in hemodialysis have been limited and inconsistent in
      their findings, whereas more compelling data are available from interventional
      studies in peritoneal dialysis. Both high and low serum bicarbonate levels
      associate with an increased risk of mortality in patients receiving hemodialysis,
      but high values are a marker for poor nutrition and comorbidity and are often
      highly variable from month to month. Measurement of pH would likely provide
      useful additional data. Concern has arisen regarding high-bicarbonate dialysate
      and dialysis-induced alkalemia, but whether these truly cause harm remains to be
      determined. The available evidence is insufficient for determining the optimal
      target for therapy at this time.

PMID- 27881611
TI  - Unusual Case of Amniotic Band Sequence.

PMID- 27881612
TI  - "What's Past Is Prologue": An Uncommon Thyroid Mass.

PMID- 27881613
TI  - Human Energy Field: A Concept Analysis.
AB  - The human energy field (HEF) as a phenomenon of interest across disciplines has
      gained increased attention over the 20th and 21st centuries. However, a concern
      has arisen that there is a lack of evidence to support the concept of the HEF as
      a phenomenon of interest to professional nurses and nursing practice. Using Chinn
      and Kramer's method of creating conceptual meaning, a concept analysis was
      conducted for the purpose of developing a conceptual definition of HEF. A
      systematic review of the literature using the CINAHL database yielded a total of
      81 articles and text sources that were determined to be relevant to the concept
      analysis. The HEF is defined as a luminous field of energy that comprises a
      person, extends beyond the physical body, and is in a continuous mutual process
      with the environmental energy field. It is a vital energy that is a continuous
      whole and is recognized by its unique pattern; it is dynamic, creative,
      nonlinear, unpredictable, and flows in lower and higher frequencies. The balanced
      HEF is characterized by flow, rhythm, symmetry, and gentle vibration.

PMID- 27881614
TI  - Performance Characteristics of a New Consensus Commercial Kit for Hepatitis D
      Virus RNA Viral Load Quantification.
AB  - Hepatitis D virus (HDV) is responsible for fulminant hepatitis and liver failure
      and accelerates evolution toward cirrhosis and hepatocellular carcinoma in
      hepatitis B virus (HBV)-infected patients. To date, treatment relies upon long
      term administration of pegylated alpha-interferon with a sustained virological
      response in 30% of the patients. Very recently, new, promising anti-HDV therapies
      have been developed and are already being used in clinical trials. HDV RNA viral
      load (HDVL) monitoring must be an integral part of the management of the infected
      patients. However, HDV genus is characterized by a high genetic variability into
      eight genotypes (HDV-1 to -8), and most available in-house or commercial assays
      are useful for only a limited subset of genotypes. Results of a comparison of the
      performance of a new kit for HDVL quantification with the consensus in-house
      assay of the French National Reference Laboratory for HDV developed in 2005 are
      reported here. A total of 611 clinical samples of all HDV genotypes with various
      HDVL values, including several consecutive samples over several years from 36
      patients, were studied. A specificity, sensitivity, and reproducibility
      evaluation was conducted using HDV-positive clinical samples, hepatitis A, B, C
      and E (HAV, HBV, HCV, and HEV, respectively) and HIV mono-infected samples, and
      the WHO HDV RNA international standard. Overall results were strictly comparable
      between the two assays (median difference, 0.07 log IU/ml), with high diagnosis
      precision and capacity. In summary, this new kit showed high performance in
      detection/quantification of HDVL, regardless of the genotype of the infecting
      strain used, and seems to be a suitable tool for patient management.

PMID- 27881615
TI  - Superiority of Digital Reverse Transcription-PCR (RT-PCR) over Real-Time RT-PCR
      for Quantitation of Highly Divergent Human Rhinoviruses.
AB  - Human rhinoviruses (HRV) comprise 3 species representing more than 150 genotypes.
      As an important human respiratory pathogen, molecular detection is an
      indispensable tool for diagnosis and surveillance. However, the sequence
      diversity of HRV genotypes poses challenges for developing robust molecular
      methods that detect all genotypes with equal efficiencies. This study compares
      the accuracies of reverse transcription-quantitative PCR (RT-qPCR) and reverse
      transcription-digital PCR (RT-dPCR) for quantifying HRV RNA using genotype
      specific primers and probes and a consensus primer/probe set targeting the 5'
      noncoding region of HRV. When using consensus primers and probes for the
      quantification of HRV, RT-dPCR outperformed RT-qPCR by consistently and
      accurately quantifying HRV RNAs across more genotype groups, despite the presence
      of up to 2 target-sequence mismatches within the primer or probe binding region.
      Because it does not rely on amplification efficiency, which can be affected by
      sequence mismatches in primer/probe binding regions, RT-dPCR may be the optimal
      molecular method for future HRV quantification studies and for quantitating other
      viruses with high sequence diversity.

PMID- 27881616
TI  - Performance of Vitek 2 for Antimicrobial Susceptibility Testing of Acinetobacter
      baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia with Vitek 2
      (2009 FDA) and CLSI M100S 26th Edition Breakpoints.
AB  - The performances of Vitek 2 AST-GN69 and AST-XN06 cards were compared to Clinical
      and Laboratory Standards Institute (CLSI) reference broth microdilution (BMD) for
      99 isolates of Pseudomonas aeruginosa, 26 Acinetobacter baumannii isolates, and
      11 Stenotrophomonas maltophilia isolates. In total, 15 antimicrobials were
      evaluated, with 11 for P. aeruginosa, 14 for A. baumannii, and 2 for S.
      maltophilia Categorical agreement (CA) was assessed using both Vitek 2
      breakpoints and 2016 CLSI M100S 26th edition breakpoints. The essential agreement
      values for P. aeruginosa, A. baumannii, and S. maltophilia were 99.5%, 99.2%, and
      100%, respectively. The CA values for P. aeruginosa, A. baumannii, and S.
      maltophilia were 94.1%, 92.7%, and 95.5%, respectively, by the Vitek 2
      breakpoints, and 93.4%, 92.3%, and 95.5%, respectively, by the CLSI breakpoints.
      Overall, the Vitek 2 performance was comparable to that of BMD using both Vitek 2
      breakpoints and 2016 CLSI M100S 26th edition breakpoints. Improved performance
      was noted for the reformulated piperacillin-tazobactam and imipenem found on the
      AST-GN69 card, with no very major or major errors noted when using the CLSI
      breakpoints.

PMID- 27881617
TI  - Can Multidrug-Resistant Candida auris Be Reliably Identified in Clinical
      Microbiology Laboratories?

PMID- 27881618
TI  - Simultaneous Screening and Quantification of Basic, Neutral and Acidic Drugs in
      Blood Using UPLC-QTOF-MS.
AB  - An analytical method using ultra performance liquid chromatography (UPLC)
      quadrupole time-of-flight mass spectrometry (QTOF-MS) was developed and validated
      for the targeted toxicological screening and quantification of commonly used
      pharmaceuticals and drugs of abuse in postmortem blood using 100 uL sample. It
      screens for more than 185 drugs and metabolites and quantifies more than 90
      drugs. The selected compounds include classes of pharmaceuticals and drugs of
      abuse such as: antidepressants, antipsychotics, analgesics (including narcotic
      analgesics), anti-inflammatory drugs, benzodiazepines, beta-blockers,
      amphetamines, new psychoactive substances (NPS), cocaine and metabolites.
      Compounds were extracted into acetonitrile using a salting-out assisted liquid
      liquid extraction (SALLE) procedure. The extracts were analyzed using a Waters
      ACQUITY UPLC coupled with a XEVO QTOF mass spectrometer. Separation of the
      analytes was achieved by gradient elution using Waters ACQUITY HSS C18 column
      (2.1 mm x 150 mm, 1.8 MUm). The mass spectrometer was operated in both positive
      and negative electrospray ionization modes. The high-resolution mass spectrometry
      (HRMS) data was acquired using a patented Waters MSE acquisition mode which
      collected low and high energy spectra alternatively during the same acquisition.
      Positive identification of target analytes was based on accurate mass
      measurements of the molecular ion, product ion, peak area ratio and retention
      times. Calibration curves were linear over the concentration range 0.05-2 mg/L
      for basic and neutral analytes and 0.1-6 mg/L for acidic analytes with the
      correlation coefficients (r2) > 0.96 for most analytes. The limits of detection
      (LOD) were between 0.001-0.05 mg/L for all analytes. Good recoveries were
      achieved ranging from 80% to 100% for most analytes using the SALLE method. The
      method was validated for sensitivity, selectivity, accuracy, precision,
      stability, carryover and matrix effects. The developed method was tested on a
      number of authentic forensic samples producing consistent results that correlated
      with results obtained from other validated methods.

PMID- 27881619
TI  - Accumulation and Determination of Phenylethanolamine A Residue in Hair of Swine
      and Sheep.
AB  - The present study proposed the use of liquid chromatography-tandem mass
      spectrometry to detect the novel beta-agonist phenylethanolamine A (PEA) in
      incurred hair samples of swine and sheep and to assess its accumulation for
      residue monitoring. The method showed good percent recoveries ranging from 93.2%
      to 102% and good coefficient of variation at <15%. The experiment was conducted
      in swine (24 treated and 4 controls) and sheep (3 treated and 1 control). PEA
      concentration was determined in hair during the treatment. High residue
      concentrations were present in hair as early as Day 24 (14.8 +/- 3.6 and 25.8 +/-
      7.6 ng/g) and Day 21 (23.4 +/- 6.6 ng/g) for swine and sheep; these residues
      persisted until withdrawal on Days 14 and 21. Results showed high PEA
      accumulation in hair, thereby indicating the use of hair as a matrix in the
      control of PEA abuse in farm animals.

PMID- 27881620
TI  - Catching Fakes: New Markers of Urine Sample Validity and Invalidity.
AB  - Urine drug testing is common for workplace drug testing, prescription management,
      emergency medicine and the criminal justice system. Unsurprisingly, with the
      significant consequences based upon the results of urine drug testing, a donor in
      need of concealing the contents of their sample is highly motivated to cheat the
      process. Procedures and safeguards ensuring sample validity are well known, and
      include measuring sample temperature at the time of collection, and laboratory
      measurements of creatinine, specific gravity and pH. Synthetic urine samples are
      available and are designed to deceive all aspects of urine drug testing,
      including validity testing. These samples are sophisticated enough to contain
      biological levels of creatinine, and are at a physiological pH and specific
      gravity. The goal of our research was to develop new procedures designed to
      distinguish authentic samples from masquerading synthetic samples. We aimed to
      identify substances in commercial synthetic urines not expected to be present in
      a biological sample distinguishing fake specimens. Additionally, we aimed to
      identify and employ endogenous compounds in addition to creatinine for
      identifying biological samples. We successfully identified two compounds present
      in synthetic urines that are not present in biological samples and use them as
      markers of invalidity. Four new endogenous markers for validity were successfully
      evaluated. Validity assessment was further aided by monitoring metabolites of
      nicotine and caffeine. When the method was applied to patient samples, 2% of
      samples were identified as inconsistent with natural urine samples, even though
      they met the current acceptance criteria for creatinine, pH and specific gravity.

PMID- 27881621
TI  - Unusual Case of Drug-Facilitated Sexual Assault using Chloroform.
AB  - Despite its well-known sedative properties, chloroform is rarely used for drug
      facilitated sexual assault (DFSA) as its administration cannot be achieved
      without the victim's knowledge: we report an unusual case of DFSA using this
      solvent. A 26-year-old woman declared that her partner get her to sleep using
      chloroform the previous night. When she waked up at 3 am, her hands were tied.
      She immediately suspected violence and sexual penetration. Toxicological blood
      screening using a liquid chromatography-electrospray coupled tandem mass
      spectrometry method highlighted the presence of bamifylline and theophylline, two
      therapeutics of asthma. A screening method for volatile substances using a
      headspace-gas chromatography coupled with mass spectrometry method showed (i) the
      presence of chloroform in blood at a concentration subsequently estimated at 580
      ug/L using an external calibration, and (ii) chloroform traces on a piece of a
      scarf brought by the patient and suspected to have been used to put her to sleep.
      These results were consistent with an exposure to chloroform by inhalation and
      demonstrate that there is no limit in the use of chemical weapons in DFSA.

PMID- 27881622
TI  - Stability of 21 Cocaine, Opioid and Benzodiazepine Drug Analytes in Spiked
      Meconium at Three Temperatures.
AB  - In this study, the stability of 21 cocaine, opioid and benzodiazepine analytes in
      spiked meconium was investigated at three storage temperatures: 4 degrees C, room
      temperature (RT), and 37 degrees C (body temperature). The drugs/metabolites
      included were hydrocodone, hydromorphone, codeine, morphine, 6-acetylmorphine (6
      AM), oxycodone, oxymorphone, cocaine, cocaethylene, benzoylecgonine, m
      hydroxybenzoylecgonine, diazepam, oxazepam, temazepam, nordiazepam,
      chlordiazepoxide, lorazepam, alprazolam, alpha-hydroxyalprazolam, clonazepam, 7
      aminoclonazepam, midazolam, alpha-hydroxymidazolam and zolpidem. Drug testing was
      performed using mass spectrometry methods that were validated for clinical use.
      After 2 weeks of storage, a substantial loss was observed in the concentrations
      of 7-aminoclonazepam (48.4% at 4 degrees C and 71.5% at RT), and chlordiazepoxide
      (59.5% at RT). A slight decrease was observed in the concentrations of alprazolam
      (20.9% at 4 degrees C), clonazepam (24.5% at 4 degrees C), chlordiazepoxide
      (23.5% at 4 degrees C), midazolam (20.8% at 4 degrees C), nordiazepam (22.8% at
      RT), and alpha-hydroxyalprazolam (20.7% at 4 degrees C). At 37 degrees C, the
      concentrations of chlordiazepoxide, 7-aminoclonazepam, lorazepam, oxazepam,
      nordiazepam and temazepam decreased by 81.4%, 86.8%, 56.5%, 59.9%, 45.4% and
      31.7%, respectively, after 2 weeks. 6-AM was observed to be unstable regardless
      of storage temperatures. For morphine, a 33.3% increase at 4 degrees C and a
      23.4% increase at RT were observed after 2 weeks, respectively, possibly due to 6
      AM degradation, while no changes >=20% were observed at 37 degrees C. All other
      analytes were stable up to 2 weeks at all three storage temperatures
      (concentration changes <20%). The stability of select drug analytes in authentic
      clinical meconium specimens was consistent with that observed in spiked meconium.
      In conclusion, some drugs in meconium may not be stable for long periods of time.
      Sample storage conditions are an important consideration in the context of
      detection windows and interpreting drug-testing results in meconium. To the best
      of our knowledge, this is the first stability study of cocaine, opioids and
      benzodiazepines in meconium concerning the effects of storage temperatures.

PMID- 27881623
TI  - Comparison of three infertility-specific measures in men and women going through
      assisted reproductive technology treatment.
AB  - We compared the psychometric properties of COMPI Fertility Problem Stress Scales,
      Fertility Problem Inventory, and Fertility Quality of Life Tool in 293 patients
      enrolled for assisted reproductive technology. COMPI Fertility Problem Stress
      Scales and Fertility Problem Inventory subscales presented higher internal
      consistency. COMPI Fertility Problem Stress Scales differentiated best between
      its domains. Fertility Problem Inventory revealed better concurrent validity.
      Fertility Quality of Life Tool presented better fit. While discrimination for
      depression was similar between measures, Fertility Quality of Life Tool was
      better at discriminating anxiety. Results suggest that while all compared
      measures are reliable and valid in assessing the psychosocial adjustment to
      infertility, the choice of measure should be based according to the assessment
      goals.

PMID- 27881624
TI  - An acceptance and commitment therapy self-help intervention for carers of
      patients in palliative care: Protocol of a feasibility randomised controlled
      trial.
AB  - Undertaking a caregiving role at end of life can have enduring psychological
      consequences for carers, including poor adjustment in bereavement. Acceptance and
      commitment therapy-based interventions have demonstrated effectiveness in helping
      people cope with a range of life challenges. This article presents the protocol
      of a feasibility randomised controlled trial of an acceptance and commitment
      therapy self-help intervention for psychological distress and grief in carers of
      patients in palliative care. We will assess feasibility and acceptability of the
      trial procedures and intervention as well as preliminary effectiveness of the
      intervention on carer well-being outcomes.

PMID- 27881625
TI  - Age-related changes in skeletal muscle function: the sum of the parts could be
      greater than the whole.

PMID- 27881626
TI  - Reply to Venturelli and colleagues.

PMID- 27881627
TI  - Sleep-related hypermotor epilepsy: Long-term outcome in a large cohort.
AB  - OBJECTIVE: To assess the long-term outcome of sleep-related hypermotor epilepsy
      (SHE). METHODS: We retrospectively reconstructed a representative cohort of
      patients diagnosed with SHE according to international diagnostic criteria, sleep
      related seizures >=75% and follow-up >=5 years. Terminal remission (TR) was
      defined as a period of >=5 consecutive years of seizure freedom at the last
      follow-up. We used Kaplan-Meier estimates to calculate the cumulative time
      dependent probability of TR and to generate survival curves. Univariate and
      multivariate Cox regression analyses were performed. RESULTS: We included 139
      patients with a 16-year median follow-up (2,414 person-years). The mean age at
      onset was 13 +/- 10 years. SHE was sporadic in 86% of cases and familial in 14%;
      16% of patients had underlying brain abnormalities. Forty-five percent of
      patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only
      in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR
      group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in
      remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10,
      20, and 30 years from inclusion. At univariate analysis, any underlying brain
      disorder (any combination of intellectual disability, perinatal insult,
      pathologic neurologic examination, and brain structural abnormalities) and
      seizures in wakefulness were more frequent among the NTR group (p = 0.028; p =
      0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95%
      confidence interval 1.26-14.05, p = 0.020) and typical SHE (hazard ratio 2.76,
      95% confidence interval 1.31-5.85, p = 0.008) were associated with TR.
      CONCLUSIONS: Our data show a poor prognosis of SHE after a long-term follow-up.
      Its outcome is primarily a function of the underlying etiology.

PMID- 27881628
TI  - Normative reference values for strength and flexibility of 1,000 children and
      adults.
AB  - OBJECTIVE: To establish reference values for isometric strength of 12 muscle
      groups and flexibility of 13 joint movements in 1,000 children and adults and
      investigate the influence of demographic and anthropometric factors. METHODS: A
      standardized reliable protocol of hand-held and fixed dynamometry for isometric
      strength of ankle, knee, hip, elbow, and shoulder musculature as well as
      goniometry for flexibility of the ankle, knee, hip, elbow, shoulder, and cervical
      spine was performed in an observational study investigating 1,000 healthy male
      and female participants aged 3-101 years. Correlation and multiple regression
      analyses were performed to identify factors independently associated with
      strength and flexibility of children, adolescents, adults, and older adults.
      RESULTS: Normative reference values of 25 strength and flexibility measures were
      generated. Strong linear correlations between age and strength were identified in
      the first 2 decades of life. Muscle strength significantly decreased with age in
      older adults. Regression modeling identified increasing height as the most
      significant predictor of strength in children, higher body mass in adolescents,
      and male sex in adults and older adults. Joint flexibility gradually decreased
      with age, with little sex difference. Waist circumference was a significant
      predictor of variability in joint flexibility in adolescents, adults, and older
      adults. CONCLUSIONS: Reference values and associated age- and sex-stratified z
      scores generated from this study can be used to determine the presence and extent
      of impairments associated with neuromuscular and other neurologic disorders,
      monitor disease progression over time in natural history studies, and evaluate
      the effect of new treatments in clinical trials.

PMID- 27881630
TI  - Corrigendum.
AB  - Chen, Jen-Hao, Linda J. Waite, and Diane S. Lauderdale. 2015. "Marriage,
      Relationship Quality, and Sleep among U.S. Older Adults." Journal of Health and
      Social Behavior 56(3): 356-77. (Original DOI: 10.1177/0022146515594631).

PMID- 27881632
TI  - Editorial Acknowledgment of Ad Hoc Reviewers.

PMID- 27881629
TI  - Risk of fractures after stroke: Results from the Ontario Stroke Registry.
AB  - OBJECTIVE: To determine the risk of fractures after stroke. METHODS: Using the
      Ontario Stroke Registry, we identified a population-based sample of consecutive
      patients seen in the emergency department or hospitalized with stroke (n =
      23,751) or TIA (n = 11,240) at any of 11 stroke centers in Ontario, Canada, and
      discharged alive between July 1, 2003, and March 31, 2012. We compared the risk
      of low-trauma fractures in patients with stroke vs those with TIA using
      propensity score methods to adjust for differences in baseline factors. Secondary
      analyses compared fracture risk poststroke with that in age-/sex-matched controls
      without stroke or TIA (n = 23,751) identified from the Ontario Registered Persons
      Database. RESULTS: The 2-year rate of fracture was 5.7% in those with stroke
      compared to 4.8% in those with TIA (adjusted cause-specific hazard ratio [aHR]
      for those with stroke vs TIA 1.32; 95% confidence interval [CI] 1.19-1.46) and
      4.1% in age-/sex-matched controls (aHR for those with stroke vs controls 1.47;
      95% CI 1.35-1.60). In the cohort with stroke, factors associated with fractures
      were older age, female sex, moderate stroke severity, prior fractures or falls,
      and preexisting osteoporosis, rheumatoid arthritis, hyperparathyroidism, and
      atrial fibrillation. CONCLUSIONS: Stroke is associated with an increased risk of
      low-trauma fractures. Individuals with stroke and additional risk factors for
      fractures may benefit from targeted screening for low bone mineral density and
      initiation of treatment for fracture prevention.

PMID- 27881633
TI  - Photo Quiz: A 4-Year-Old Boy Vomits on His Sister.

PMID- 27881634
TI  - The Brief Case: Neonatal Meningitis Caused by Listeria monocytogenes Diagnosed by
      Multiplex Molecular Panel.

PMID- 27881635
TI  - Commutability of the World Health Organization International Standard for Human
      Cytomegalovirus: Standard or Assay.

PMID- 27881636
TI  - Reply to "Commutability of the World Health Organization International Standard
      for Human Cytomegalovirus: Standard or Assay".

PMID- 27881637
TI  - Closing the Brief Case: Neonatal Meningitis Caused by Listeria monocytogenes
      Diagnosed by Multiplex Molecular Panel.

PMID- 27881638
TI  - Answer to December 2016 Photo Quiz.

PMID- 27881640
TI  - Polymer-based material containing calcium phosphate particles functionalized with
      a dimethacrylate monomer for use in restorative dentistry.
AB  - Dicalcium phosphate dihydrate particles functionalized with triethyleneglycol
      dimethacrylate were synthesized and added to a photocurable mixture of bisphenol
      A glycidyl dimethacrylate and triethyleneglycol dimethacrylate with the purpose
      of developing a resin composite capable of releasing calcium and phosphate ions
      to foster dental remineralization. Particle functionalization would minimize the
      deleterious effect of adding low cohesive strength nano-structured particles with
      no chemical interaction with the organic matrix on the material's mechanical
      properties. The results showed that calcium release over 28 days was not impaired
      by particle functionalization. A statistically significant 32% increase in
      strength was recorded with the use of functionalized dicalcium phosphate
      dihydrate in comparison to the material containing non-functionalized particles.
      However, the strength of the unfilled resin was not matched by the composite with
      functionalized particles. Elastic modulus increased with particle incorporation,
      regardless of functionalization. Degree of conversion and optical properties
      (total transmittance and color change/DeltaE) of the resin-based materials were
      not affected by the addition of dicalcium phosphate dihydrate particles
      (functionalized or not).

PMID- 27881639
TI  - Enhancement of osseointegration by direct coating of rhBMP-2 on target-ion
      induced plasma sputtering treated SLA surface for dental application.
AB  - Owing to the excellent bioactive properties of recombinant human bone
      morphogenetic proteins (rhBMPs), dentistry considers them as a fascinating
      adjuvant alternative for enhancing bone regeneration and bone-to-implant junction
      in the early implantation stages. However, stable loading and delivery efficiency
      of rhBMPs on the implant surfaces involve major concerns because of the harsh
      wearing condition under load during implantation. In this study, to achieve
      successful rhBMP-2 delivery, a nanoporous surface structure is introduced on the
      sandblasting with large grit and acid-etching (SLA)-treated titanium (Ti) surface
      via the tantalum (Ta) target-ion induced plasma sputtering (TIPS) technique.
      Unlike oxidation-induced surface nanoporous fabrications on a Ti surface, TIPS
      treated surfaces provide excellent structural unity of the nanoporous structure
      with the substrate due to their etching-based fabrication mechanism. SLA/TIPS
      treated Ti exhibits distinct nanoporous structures on the microscale surface
      geometry and better hydrophilicity compared with SLA-treated Ti. A sufficiently
      empty nanoporous surface structure combined with the hydrophilic property of
      SLA/TIPS-treated Ti facilitates the formation of a thick and uniform coating
      layer of rhBMP-2 on the surface without any macro- and microcoagulation. Compared
      with the SLA-treated Ti surface, the amount of coated rhBMP-2 increases up to 63%
      on the SLA/TIPS-treated Ti surface. As a result, the in vitro pre-osteoblast cell
      response of the SLA/TIPS-treated Ti surface, especially cell adhesion and
      differentiation behaviors, improves remarkably. A bone-regenerating direct
      comparison between the rhBMP-2-coated SLA-treated and SLA/TIPS-treated Ti is
      conducted on a defective dog mandible model. After 8 weeks of implantation
      surgery, SLA/TIPS-treated Ti with rhBMP-2 exhibits a better degree of contact
      area for the implanted bone, which mineralizes new bones around the implant.
      Quantitative results of bone-in-contact ratio and new bone volume also show
      significantly higher values for the SLA/TIPS-treated Ti with the rhBMP-2
      specimen. These results confirm that an SLA/TIPS-treated surface is a suitable
      rhBMP-2 carrier for a dental implant to achieve early and strong osseointegration
      of Ti dental implants.

PMID- 27881641
TI  - Folic acid-conjugated soybean protein-based nanoparticles mediate efficient
      antitumor ability in vitro.
AB  - In this study, soy protein isolate was hydrolyzed by compound enzymes to give
      aqueous soy protein with low molecular weights. Folic acid modified and free soy
      protein nanoparticles were successfully prepared by a desolvation method as
      target-specific drug delivery, respectively. Ultraviolet spectrophotometry
      demonstrated that folic acid was successfully grafted onto soy protein. The shape
      and size of folic acid modified soy protein nanoparticles were detected by
      transmission electron microscopy, scanning electron microscope, and dynamic light
      scattering. In addition, a series of characteristics including kinetic stability,
      pH stability, and time stability were also performed. Doxorubicin was
      successfully loaded into folic acid modified soy protein nanoparticles, and the
      encapsulation and loading efficiencies were 96.7% and 23%, respectively.
      Doxorubicin-loaded folic acid modified soy protein nanoparticles exhibited faster
      drug release rate than soy protein nanoparticles in PBS solution (pH = 5). The
      tumor penetration and antitumor experiments were done using three-dimensional
      multicellular tumor spheroids as the in vitro model. The results proved that
      folic acid modified soy protein nanoparticles display higher penetration and
      accumulation than soy protein nanoparticles, therefore possessing efficient
      growth inhibitory ability against multicellular tumor spheroids.

PMID- 27881642
TI  - Clinoptilolite/PCL-PEG-PCL composite scaffolds for bone tissue engineering
      applications.
AB  - The aim of this study was to prepare and characterize highly porous
      clinoptilolite/poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon
      caprolactone) composite scaffolds. Scaffolds with different clinoptilolite
      contents (10% and 20%) were fabricated with reproducible solvent-free powder
      compression/particulate leaching technique. The scaffolds had interconnective
      porosity in the range of 55-76%. Clinoptilolite/poly(epsilon-caprolactone)
      poly(ethylene glycol)-poly(epsilon-caprolactone) scaffolds showed negligible
      degradation within eight weeks and displayed less water uptake and higher
      bioactivity than poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon
      caprolactone) scaffolds. The presence of clinoptilolite improved the mechanical
      properties. Highest compressive strength (5.6 MPa) and modulus (114.84 MPa) were
      reached with scaffold group containing 20% clinoptilolite. In vitro protein
      adsorption capacity of the scaffolds was also higher for
      clinoptilolite/poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon
      caprolactone) scaffolds. These scaffolds had 0.95 mg protein/g scaffold
      adsorption capacity and also higher osteoinductivity in terms of enhanced ALP,
      OSP activities and intracellular calcium deposition. Stoichiometric apatite
      deposition (Ca/P=1.686) was observed during cellular proliferation analysis with
      human fetal osteoblasts cells. Thus, it can be suggested that
      clinoptilolite/poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon
      caprolactone) composite scaffolds could be promising carriers for enhancement of
      bone regeneration in bone tissue engineering applications.

PMID- 27881643
TI  - Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated
      alpha-Tubulin Enhances Viral Replication.
AB  - : Viral inclusion bodies (IBs), or replication factories, are unique structures
      generated by viral proteins together with some cellular proteins as a platform
      for efficient viral replication, but little is known about the mechanism
      underlying IB formation and fusion. Our previous study demonstrated that the
      interaction between the nucleoprotein (N) and phosphoprotein (P) of human
      parainfluenza virus type 3 (HPIV3), an enveloped virus with great medical impact,
      can form IBs. In this study, we found that small IBs can fuse with each other to
      form large IBs that enhance viral replication. Furthermore, we found that
      acetylated alpha-tubulin interacts with the N-P complex and colocalizes with IBs
      of HPIV3 but does not interact with the N-P complex of human respiratory
      syncytial virus or vesicular stomatitis virus and does not colocalize with IBs of
      human respiratory syncytial virus. Most importantly, enhancement of alpha-tubulin
      acetylation using the pharmacological inhibitor trichostatin A (TSA), RNA
      interference (RNAi) knockdown of the deacetylase enzymes histone deacetylase 6
      (HDAC6) and sirtuin 2 (SIRT2), or expression of alpha-tubulin acetyltransferase 1
      (alpha-TAT1) resulted in the fusion of small IBs into large IBs and effective
      viral replication. In contrast, suppression of acetylation of alpha-tubulin by
      overexpressing HDAC6 and SIRT2 profoundly inhibited the fusion of small IBs and
      viral replication. Our findings offer previously unidentified mechanistic
      insights into the regulation of viral IB fusion by acetylated alpha-tubulin,
      which is critical for viral replication. IMPORTANCE: Inclusion bodies (IBs) are
      unique structures generated by viral proteins and some cellular proteins as a
      platform for efficient viral replication. Human parainfluenza virus type 3
      (HPIV3) is a nonsegmented single-stranded RNA virus that mainly causes lower
      respiratory tract disease in infants and young children. However, no vaccines or
      antiviral drugs for HPIV3 are available. Therefore, understanding virus-host
      interactions and developing new antiviral strategies are increasingly important.
      Acetylation on lysine (K) 40 of alpha-tubulin is an evolutionarily conserved
      modification and plays an important role in many cellular processes, but its role
      in viral IB dynamics has not been fully explored. To our knowledge, our findings
      are the first to show that acetylated alpha-tubulin enhances viral replication by
      regulating HPIV3 IB fusion.

PMID- 27881644
TI  - Suppression of Adenovirus Replication by Cardiotonic Steroids.
AB  - : The dependence of adenovirus on the host pre-RNA splicing machinery for
      expression of its complete genome potentially makes it vulnerable to modulators
      of RNA splicing, such as digoxin and digitoxin. Both drugs reduced the yields of
      four human adenoviruses (HAdV-A31, -B35, and -C5 and a species D conjunctivitis
      isolate) by at least 2 to 3 logs by affecting one or more steps needed for genome
      replication. Immediate early E1A protein levels are unaffected by the drugs, but
      synthesis of the delayed protein E4orf6 and the major late capsid protein hexon
      is compromised. Quantitative reverse transcription-PCR (qRT-PCR) analyses
      revealed that both drugs altered E1A RNA splicing (favoring the production of 13S
      over 12S RNA) early in infection and partially blocked the transition from 12S
      and 13S to 9S RNA at late stages of virus replication. Expression of multiple
      late viral protein mRNAs was lost in the presence of either drug, consistent with
      the observed block in viral DNA replication. The antiviral effect was dependent
      on the continued presence of the drug and was rapidly reversible. RIDK34, a
      derivative of convallotoxin, although having more potent antiviral activity, did
      not show an improved selectivity index. All three drugs reduced metabolic
      activity to some degree without evidence of cell death. By blocking adenovirus
      replication at one or more steps beyond the onset of E1A expression and prior to
      genome replication, digoxin and digitoxin show potential as antiviral agents for
      treatment of serious adenovirus infections. Furthermore, understanding the
      mechanism(s) by which digoxin and digitoxin inhibit adenovirus replication will
      guide the development of novel antiviral therapies. IMPORTANCE: Despite human
      adenoviruses being a common and, in some instances, life-threating pathogen in
      humans, there are few well-tolerated therapies. In this report, we demonstrate
      that two cardiotonic steroids already in use in humans, digoxin and digitoxin,
      are potent inhibitors of multiple adenovirus species. A synthetic derivative of
      the cardiotonic steroid convallotoxin was even more potent than digoxin and
      digitoxin when tested with HAdV-C5. These drugs alter the cascade of adenovirus
      gene expression, acting after initiation of early gene expression to block viral
      DNA replication and synthesis of viral structural proteins. These findings
      validate a novel approach to treating adenovirus infections through the
      modulation of host cell processes.

PMID- 27881645
TI  - Phylogenetic Diversity of Koala Retrovirus within a Wild Koala Population.
AB  - : Koala populations are in serious decline across many areas of mainland
      Australia, with infectious disease a contributing factor. Koala retrovirus (KoRV)
      is a gammaretrovirus present in most wild koala populations and captive colonies.
      Five subtypes of KoRV (A to E) have been identified based on amino acid sequence
      divergence in a hypervariable region of the receptor binding domain of the
      envelope protein. However, analysis of viral genetic diversity has been conducted
      primarily on KoRV in captive koalas housed in zoos in Japan, the United States,
      and Germany. Wild koalas within Australia have not been comparably assessed. Here
      we report a detailed analysis of KoRV genetic diversity in samples collected from
      18 wild koalas from southeast Queensland. By employing deep sequencing we
      identified 108 novel KoRV envelope sequences and determined their phylogenetic
      diversity. Genetic diversity in KoRV was abundant and fell into three major
      groups; two comprised the previously identified subtypes A and B, while the third
      contained the remaining hypervariable region subtypes (C, D, and E) as well as
      four hypervariable region subtypes that we newly define here (F, G, H, and I). In
      addition to the ubiquitous presence of KoRV-A, which may represent an exclusively
      endogenous variant, subtypes B, D, and F were found to be at high prevalence,
      while subtypes G, H, and I were present in a smaller number of animals.
      IMPORTANCE: Koala retrovirus (KoRV) is thought to be a significant contributor to
      koala disease and population decline across mainland Australia. This study is the
      first to determine KoRV subtype prevalence among a wild koala population, and it
      significantly expands the total number of KoRV sequences available, providing a
      more precise picture of genetic diversity. This understanding of KoRV subtype
      prevalence and genetic diversity will be important for conservation efforts
      attempting to limit the spread of KoRV. Furthermore, KoRV is one of the only
      retroviruses shown to exist in both endogenous (transmitted vertically to
      offspring in the germ line DNA) and exogenous (horizontally transmitted between
      infected individuals) forms, a division of fundamental evolutionary importance.

PMID- 27881646
TI  - Activation and Inactivation of Primary Human Immunodeficiency Virus Envelope
      Glycoprotein Trimers by CD4-Mimetic Compounds.
AB  - : Human immunodeficiency virus type 1 (HIV-1) entry into cells is mediated by the
      viral envelope glycoproteins (Env), a trimer of three gp120 exterior
      glycoproteins, and three gp41 transmembrane glycoproteins. The metastable Env is
      triggered to undergo entry-related conformational changes when gp120 binds
      sequentially to the receptors, CD4 and CCR5, on the target cell. Small-molecule
      CD4-mimetic compounds (CD4mc) bind gp120 and act as competitive inhibitors of
      gp120-CD4 engagement. Some CD4mc have been shown to trigger Env prematurely,
      initially activating Env function, followed by rapid and irreversible
      inactivation. Here, we study CD4mc with a wide range of anti-HIV-1 potencies and
      demonstrate that all tested CD4mc are capable of activating as well as
      inactivating Env function. Biphasic dose-response curves indicated that the
      occupancy of the protomers in the Env trimer governs viral activation versus
      inactivation. One CD4mc bound per Env trimer activated HIV-1 infection. Envs with
      two CD4mc bound were activated for infection of CD4-negative, CCR5-positive
      cells, but the infection of CD4-positive, CCR5-positive cells was inhibited.
      Virus was inactivated when all three Env protomers were occupied by the CD4mc,
      and gp120 shedding from the Env trimer was increased in the presence of some
      CD4mc. Env reactivity and the on rates of CD4mc binding to the Env trimer were
      found to be important determinants of the potency of activation and entry
      inhibition. Cross-sensitization of Env protomers that do not bind the CD4mc to
      neutralization by an anti-V3 antibody was not evident. These insights into the
      mechanism of antiviral activity of CD4mc should assist efforts to optimize their
      potency and utility. IMPORTANCE: The trimeric envelope glycoproteins of human
      immunodeficiency virus type 1 (HIV-1) mediate virus entry into host cells.
      Binding to the host cell receptors, CD4 and CCR5, triggers changes in the
      conformation of the HIV-1 envelope glycoprotein trimer important for virus entry.
      Small-molecule CD4-mimetic compounds inhibit HIV-1 infection by multiple
      mechanisms: (i) direct blockade of the interaction between the gp120 exterior
      envelope glycoprotein and CD4; (ii) premature triggering of conformational
      changes in the envelope glycoproteins, leading to irreversible inactivation; and
      (iii) exposure of cryptic epitopes to antibodies, allowing virus neutralization.
      The consequences of the binding of the CD4-mimetic compound to the HIV-1 envelope
      glycoproteins depends upon how many of the three subunits of the trimer are bound
      and upon the propensity of the envelope glycoproteins to undergo conformational
      changes. Understanding the mechanistic factors that influence the activity of CD4
      mimetic compounds can help to improve their potency and coverage of diverse HIV-1
      strains.

PMID- 27881647
TI  - Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of
      Nitric Oxide Production.
AB  - : Enteric caliciviruses in the genera Norovirus and Sapovirus are important
      pathogens that cause severe acute gastroenteritis in both humans and animals.
      Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are
      known to play important roles in the modulation of both the host response to
      infection and the replicative cycles of several viruses. However, the precise
      mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication
      remains largely unknown. In this study, infection with porcine sapovirus (PSaV)
      strain Cowden, the only cultivable virus within the genus Sapovirus, markedly
      increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with
      only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells
      with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or
      small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced
      PGE2 production, as well as PSaV replication. Expression of the viral proteins
      VPg and ProPol was associated with activation of the COX/PGE2 pathway. We
      observed that pharmacological inhibition of COX-2 dramatically increased NO
      production, causing a reduction in PSaV replication that could be restored by
      inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine
      ester. This study identified a pivotal role for the COX/PGE2 pathway in the
      regulation of NO production during the sapovirus life cycle, providing new
      insights into the life cycle of this poorly characterized family of viruses. Our
      findings also reveal potential new targets for treatment of sapovirus infection.
      IMPORTANCE: Sapoviruses are among the major etiological agents of acute
      gastroenteritis in both humans and animals, but little is known about sapovirus
      host factor requirements. Here, using only cultivable porcine sapovirus (PSaV)
      strain Cowden, we demonstrate that PSaV induced the vitalization of the
      cyclooxygenase (COX) and prostaglandin E2 (PGE2) pathway. Targeting of COX-1/2
      using nonsteroidal anti-inflammatory drugs (NSAIDs) such as the COX-1/2 inhibitor
      indomethacin and the COX-2-specific inhibitors NS-398 and celecoxib or siRNAs
      targeting COXs, inhibited PSaV replication. Expression of the viral proteins VPg
      and ProPol was associated with activation of the COX/PGE2 pathway. We further
      demonstrate that the production of PGE2 provides a protective effect against the
      antiviral effector mechanism of nitric oxide. Our findings uncover a new
      mechanism by which PSaV manipulates the host cell to provide an environment
      suitable for efficient viral growth, which in turn can be a new target for
      treatment of sapovirus infection.

PMID- 27881648
TI  - Modeling Severe Fever with Thrombocytopenia Syndrome Virus Infection in Golden
      Syrian Hamsters: Importance of STAT2 in Preventing Disease and Effective
      Treatment with Favipiravir.
AB  - : Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne
      disease endemic in parts of Asia. The etiologic agent, SFTS virus (SFTSV; family
      Bunyaviridae, genus Phlebovirus) has caused significant morbidity and mortality
      in China, South Korea, and Japan, with key features of disease being intense
      fever, thrombocytopenia, and leukopenia. Case fatality rates are estimated to be
      in the 30% range, and no antivirals or vaccines are approved for use for
      treatment and prevention of SFTS. There is evidence that in human cells, SFTSV
      sequesters STAT proteins in replication complexes, thereby inhibiting type I
      interferon signaling. Here, we demonstrate that hamsters devoid of functional
      STAT2 are highly susceptible to as few as 10 PFU of SFTSV, with animals generally
      succumbing within 5 to 6 days after subcutaneous challenge. The disease included
      marked thrombocytopenia and inflammatory disease characteristic of the condition
      in humans. Infectious virus titers were present in the blood and most tissues 3
      days after virus challenge, and severe inflammatory lesions were found in the
      spleen and liver samples of SFTSV-infected hamsters. We also show that SFTSV
      infection in STAT2 knockout (KO) hamsters is responsive to favipiravir treatment,
      which protected all animals from lethal disease and reduced serum and tissue
      viral loads by 3 to 6 orders of magnitude. Taken together, our results provide
      additional insights into the pathogenesis of SFTSV infection and support the use
      of the newly described STAT2 KO hamster model for evaluation of promising
      antiviral therapies. IMPORTANCE: Severe fever with thrombocytopenia syndrome
      (SFTS) is an emerging viral disease for which there are currently no therapeutic
      options or available vaccines. The causative agent, SFTS virus (SFTSV), is
      present in China, South Korea, and Japan, and infections requiring medical
      attention result in death in as many as 30% of the cases. Here, we describe a
      novel model of SFTS in hamsters genetically engineered to be deficient in a
      protein that helps protect humans and animals against viral infections. These
      hamsters were found to be susceptible to SFTSV and share disease features
      associated with the disease in humans. Importantly, we also show that SFTSV
      infection in hamsters can be effectively treated with a broad-spectrum antiviral
      drug approved for use in Japan. Our findings suggest that the new SFTS model will
      be an excellent resource to better understand SFTSV infection and disease as well
      as a valuable tool for evaluating promising antiviral drugs.

PMID- 27881649
TI  - The Many Faces of the Flavivirus NS5 Protein in Antagonism of Type I Interferon
      Signaling.
AB  - The vector-borne flaviviruses cause severe disease in humans on every inhabited
      continent on earth. Their transmission by arthropods, particularly mosquitoes,
      facilitates large emergence events such as witnessed with Zika virus (ZIKV) or
      West Nile virus in the Americas. Every vector-borne flavivirus examined thus far
      that causes disease in humans, from dengue virus to ZIKV, antagonizes the host
      type I interferon (IFN-I) response by preventing JAK-STAT signaling, suggesting
      that suppression of this pathway is an important determinant of infection. The
      most direct and potent viral inhibitor of this pathway is the nonstructural
      protein NS5. However, the mechanisms utilized by NS5 from different flaviviruses
      are often quite different, sometimes despite close evolutionary relationships
      between viruses. The varied mechanisms of NS5 as an IFN-I antagonist are also
      surprising given that the evolution of NS5 is restrained by the requirement to
      maintain function of two enzymatic activities critical for virus replication, the
      methyltransferase and RNA-dependent RNA polymerase. This review discusses the
      different strategies used by flavivirus NS5 to evade the antiviral effects of IFN
      I and how this information can be used to better model disease and develop
      antiviral countermeasures.

PMID- 27881650
TI  - Mechanism of Enhanced HIV Restriction by Virion Coencapsidated Cytidine
      Deaminases APOBEC3F and APOBEC3G.
AB  - : The APOBEC3 (A3) enzymes, A3G and A3F, are coordinately expressed in CD4+ T
      cells and can become coencapsidated into HIV-1 virions, primarily in the absence
      of the viral infectivity factor (Vif). A3F and A3G are deoxycytidine deaminases
      that inhibit HIV-1 replication by inducing guanine-to-adenine hypermutation
      through deamination of cytosine to form uracil in minus-strand DNA. The effect of
      the simultaneous presence of both A3G and A3F on HIV-1 restriction ability is not
      clear. Here, we used a single-cycle infectivity assay and biochemical analyses to
      determine if coencapsidated A3G and A3F differ in their restriction capacity from
      A3G or A3F alone. Proviral DNA sequencing demonstrated that compared to each A3
      enzyme alone, A3G and A3F, when combined, had a coordinate effect on
      hypermutation. Using size exclusion chromatography, rotational anisotropy, and in
      vitro deamination assays, we demonstrate that A3F promotes A3G deamination
      activity by forming an A3F/G hetero-oligomer in the absence of RNA which is more
      efficient at deaminating cytosines. Further, A3F caused the accumulation of
      shorter reverse transcripts due to decreasing reverse transcriptase efficiency,
      which would leave single-stranded minus-strand DNA exposed for longer periods of
      time, enabling more deamination events to occur. Although A3G and A3F are known
      to function alongside each other, these data provide evidence for an A3F/G hetero
      oligomeric A3 with unique properties compared to each individual counterpart.
      IMPORTANCE: The APOBEC3 enzymes APOBEC3F and APOBEC3G act as a barrier to HIV-1
      replication in the absence of the HIV-1 Vif protein. After APOBEC3 enzymes are
      encapsidated into virions, they deaminate cytosines in minus-strand DNA, which
      forms promutagenic uracils that induce transition mutations or proviral DNA
      degradation. Even in the presence of Vif, footprints of APOBEC3-catalyzed
      deaminations are found, demonstrating that APOBEC3s still have discernible
      activity against HIV-1 in infected individuals. We undertook a study to better
      understand the activity of coexpressed APOBEC3F and APOBEC3G. The data
      demonstrate that an APOBEC3F/APOBEC3G hetero-oligomer can form that has unique
      properties compared to each APOBEC3 alone. This hetero-oligomer has increased
      efficiency of virus hypermutation, raising the idea that we still may not fully
      realize the antiviral mechanisms of endogenous APOBEC3 enzymes. Hetero
      oligomerization may be a mechanism to increase their antiviral activity in the
      presence of Vif.

PMID- 27881651
TI  - Alternative Polyadenylation of Human Bocavirus at Its 3' End Is Regulated by
      Multiple Elements and Affects Capsid Expression.
AB  - : Alternative processing of human bocavirus (HBoV) P5 promoter-transcribed RNA is
      critical for generating the structural and nonstructural protein-encoding mRNA
      transcripts. The regulatory mechanism by which HBoV RNA transcripts are
      polyadenylated at proximal [(pA)p] or distal [(pA)d] polyadenylation sites is
      still unclear. We constructed a recombinant HBoV infectious clone to study the
      alternative polyadenylation regulation of HBoV. Surprisingly, in addition to the
      reported distal polyadenylation site, (pA)d, a novel distal polyadenylation site,
      (pA)d2, which is located in the right-end hairpin (REH), was identified during
      infectious clone transfection or recombinant virus infection. (pA)d2 does not
      contain typical hexanucleotide polyadenylation signal, upstream elements (USE),
      or downstream elements (DSE) according to sequence analysis. Further study showed
      that HBoV nonstructural protein NS1, REH, and cis elements of (pA)d were
      necessary and sufficient for efficient polyadenylation at (pA)d2. The distance
      and sequences between (pA)d and (pA)d2 also played a key role in the regulation
      of polyadenylation at (pA)d2. Finally, we demonstrated that efficient
      polyadenylation at (pA)d2 resulted in increased HBoV capsid mRNA transcripts and
      protein translation. Thus, our study revealed that all the bocaviruses have
      distal poly(A) signals on the right-end palindromic terminus, and alternative
      polyadenylation at the HBoV 3' end regulates its capsid expression. IMPORTANCE:
      The distal polyadenylation site, (pA)d, of HBoV is located about 400 nucleotides
      (nt) from the right-end palindromic terminus, which is different from those of
      bovine parvovirus (BPV) and canine minute virus (MVC) in the same genus whose
      distal polyadenylation is located in the right-end stem-loop structure. A novel
      polyadenylation site, (pA)d2, was identified in the right-end hairpin of HBoV
      during infectious clone transfection or recombinant virus infection. Sequence
      analysis showed that (pA)d2 does not contain typical polyadenylation signals, and
      the last 42 nt form a stem-loop structure which is almost identical to that of
      MVC. Further study showed that NS1, REH, and cis elements of (pA)d are required
      for efficient polyadenylation at (pA)d2. Polyadenylation at (pA)d2 enhances
      capsid expression. Our study demonstrates alternative polyadenylation at the 3'
      end of HBoV and suggests an additional mechanism by which capsid expression is
      regulated.

PMID- 27881652
TI  - Inhibition of Human Cytomegalovirus pUL89 Terminase Subunit Blocks Virus
      Replication and Genome Cleavage.
AB  - : The human cytomegalovirus terminase complex cleaves concatemeric genomic DNA
      into unit lengths during genome packaging and particle assembly. This process is
      an attractive drug target because cleavage of concatemeric DNA is not required in
      mammalian cell DNA replication, indicating that drugs targeting the terminase
      complex could be safe and selective. One component of the human cytomegalovirus
      terminase complex, pUL89, provides the endonucleolytic activity for genome
      cleavage, and the domain responsible is reported to have an RNase H-like fold. We
      hypothesize that the pUL89 endonuclease activity is inhibited by known RNase H
      inhibitors. Using a novel enzyme-linked immunosorbent assay (ELISA) format as a
      screening assay, we found that a hydroxypyridonecarboxylic acid compound,
      previously reported to be an inhibitor of human immunodeficiency virus RNase H,
      inhibited pUL89 endonuclease activity at low-micromolar concentrations. Further
      characterization revealed that this pUL89 endonuclease inhibitor blocked human
      cytomegalovirus replication at a relatively late time point, similarly to other
      reported terminase complex inhibitors. Importantly, this inhibitor also prevented
      the cleavage of viral genomic DNA in infected cells. Taken together, these
      results substantiate our pharmacophore hypothesis and validate our ligand-based
      approach toward identifying novel inhibitors of pUL89 endonuclease. IMPORTANCE:
      Human cytomegalovirus infection in individuals lacking a fully functioning immune
      system, such as newborns and transplant patients, can have severe and
      debilitating consequences. The U.S. Food and Drug Administration-approved anti
      human cytomegalovirus drugs mainly target the viral polymerase, and resistance to
      these drugs has appeared. Therefore, anti-human cytomegalovirus drugs from novel
      targets are needed for use instead of, or in combination with, current polymerase
      inhibitors. pUL89 is a viral ATPase and endonuclease and is an attractive target
      for anti-human cytomegalovirus drug development. We identified and characterized
      an inhibitor of pUL89 endonuclease activity that also inhibits human
      cytomegalovirus replication in cell culture. pUL89 endonuclease, therefore,
      should be explored as a potential target for antiviral development against human
      cytomegalovirus.

PMID- 27881653
TI  - MicroRNA 373 Facilitates the Replication of Porcine Reproductive and Respiratory
      Syndrome Virus by Its Negative Regulation of Type I Interferon Induction.
AB  - : MicroRNAs (miRNAs) play an important role in the regulation of immune
      responses. Previous studies have indicated that dysregulating the miRNAs leads to
      the immunosuppression of porcine reproductive and respiratory syndrome virus
      (PRRSV). However, it is not clear how PRRSV regulates the expression of host
      miRNA, which may lead to immune escape or promote the replication of the virus.
      The present work suggests that PRRSV upregulated the expression of miR-373
      through elevating the expression of specificity protein 1 (Sp1) in MARC-145
      cells. Furthermore, this work demonstrated that miR-373 promoted the replication
      of PRRSV, since miR-373 was a novel negative miRNA for the production of beta
      interferon (IFN-beta) by targeting nuclear factor IA (NFIA), NFIB, interleukin-1
      receptor-associated kinase 1 (IRAK1), IRAK4, and interferon regulatory factor 1
      (IRF1). We also found that both NFIA and NFIB were novel proteins for inducing
      the production of IFN-beta, and both of them could inhibit the replication of
      PRRSV. In conclusion, PRRSV upregulated the expression of miR-373 by elevating
      the expression of Sp1 and hijacked the host miR-373 to promote the replication of
      PRRSV by negatively regulating the production of IFN-beta. IMPORTANCE: PRRSV
      causes one of the most economically devastating diseases of swine, and there is
      no effective method for controlling PRRSV. It is not clear how PRRSV inhibits the
      host's immune response and induces persistent infection. Previous studies have
      shown that PRRSV inhibited the production of type I IFN, and the treatment of
      type I IFN could efficiently inhibit the replication of PRRSV, so it will be
      helpful to design new methods of controlling PRRSV by understanding the molecular
      mechanism by which PRRSV modulated the production of IFN. The current work shows
      that miR-373, upregulated by PRRSV, promotes PRRSV replication, since miR-373
      impaired the production of IFN-beta by targeting NFIA, NFIB, IRAK1, IRAK4, and
      IRF1, and both NFIA and NFIB were antiviral proteins to PRRSV. In conclusion,
      this paper revealed a novel mechanism of PRRSV that impaired the production of
      type I IFN by upregulating miR-373 expression in MARC-145 cells.

PMID- 27881654
TI  - Identification of New World Quails Susceptible to Infection with Avian Leukosis
      Virus Subgroup J.
AB  - : The J subgroup of avian leukosis virus (ALV-J) infects domestic chickens,
      jungle fowl, and turkeys. This virus enters the host cell through a receptor
      encoded by the tvj locus and identified as Na+/H+ exchanger 1. The resistance to
      avian leukosis virus subgroup J in a great majority of galliform species has been
      explained by deletions or substitutions of the critical tryptophan 38 in the
      first extracellular loop of Na+/H+ exchanger 1. Because there are concerns of
      transspecies virus transmission, we studied natural polymorphisms and
      susceptibility/resistance in wild galliforms and found the presence of tryptophan
      38 in four species of New World quails. The embryo fibroblasts of New World
      quails are susceptible to infection with avian leukosis virus subgroup J, and the
      cloned Na+/H+ exchanger 1 confers susceptibility on the otherwise resistant host.
      New World quails are also susceptible to new avian leukosis virus subgroup J
      variants but resistant to subgroups A and B and weakly susceptible to subgroups C
      and D of avian sarcoma/leukosis virus due to obvious defects of the respective
      receptors. Our results suggest that the avian leukosis virus subgroup J could be
      transmitted to New World quails and establish a natural reservoir of circulating
      virus with a potential for further evolution. IMPORTANCE: Since its spread in
      broiler chickens in China and Southeast Asia in 2000, ALV-J remains a major
      enzootic challenge for the poultry industry. Although the virus diversifies
      rapidly in the poultry, its spillover and circulation in wild bird species has
      been prevented by the resistance of most species to ALV-J. It is, nevertheless,
      important to understand the evolution of the virus and its potential host range
      in wild birds. Because resistance to avian retroviruses is due particularly to
      receptor incompatibility, we studied Na+/H+ exchanger 1, the receptor for ALV-J.
      In New World quails, we found a receptor compatible with virus entry, and we
      confirmed the susceptibilities of four New World quail species in vitro We
      propose that a prospective molecular epidemiology study be conducted to identify
      species with the potential to become reservoirs for ALV-J.

PMID- 27881655
TI  - Porcine Reproductive and Respiratory Syndrome Virus nsp1alpha Inhibits NF-kappaB
      Activation by Targeting the Linear Ubiquitin Chain Assembly Complex.
AB  - : Linear ubiquitination, a newly discovered posttranslational modification, is
      catalyzed by the linear ubiquitin chain assembly complex (LUBAC), which is
      composed of three subunits: one catalytic subunit HOIP and two accessory
      molecules, HOIL-1L and SHARPIN. Accumulating evidence suggests that linear
      ubiquitination plays a crucial role in innate immune signaling and especially in
      the activation of the NF-kappaB pathway by conjugating linear polyubiquitin
      chains to NF-kappaB essential modulator (NEMO, also called IKKgamma), the
      regulatory subunit of the IKK complex. Porcine reproductive and respiratory
      syndrome virus (PRRSV), an Arterivirus that has devastated the swine industry
      worldwide, is an ideal model to study the host's disordered inflammatory
      responses after viral infection. Here, we found that LUBAC-induced NF-kappaB and
      proinflammatory cytokine expression can be inhibited in the early phase of PRRSV
      infection. Screening the PRRSV-encoded proteins showed that nonstructural protein
      1alpha (nsp1alpha) suppresses LUBAC-mediated NF-kappaB activation and its CTE
      domain is required for the inhibition. Mechanistically, nsp1alpha binds to
      HOIP/HOIL-1L and impairs the interaction between HOIP and SHARPIN, thus reducing
      the LUBAC-dependent linear ubiquitination of NEMO. Moreover, PRRSV infection also
      blocks LUBAC complex formation and NEMO linear-ubiquitination, the important step
      for transducing NF-kappaB signaling. This unexpected finding demonstrates a
      previously unrecognized role of PRRSV nsp1alpha in modulating LUBAC signaling and
      explains an additional mechanism of immune modulation by PRRSV. IMPORTANCE:
      Porcine reproductive and respiratory syndrome (PRRS) is one of the most important
      veterinary infectious diseases in countries with intensive swine industries. PRRS
      virus (PRRSV) infection usually suppresses proinflammatory cytokine expression in
      the early stage of infection, whereas it induces an inflammatory storm in the
      late stage. However, precisely how the virus is capable of doing so remains
      obscure. In this study, we found that by blocking the interaction of its
      catalytic subunit HOIP and accessory molecule SHARPIN, PRRSV can suppress NF
      kappaB signal transduction in the early stage of infection. Our findings not only
      reveal a novel mechanism evolved by PRRSV to regulate inflammatory responses but
      also highlight the important role of linear ubiquitination modification during
      virus infection.

PMID- 27881656
TI  - Infectious Bursal Disease Virus Activates c-Src To Promote alpha4beta1 Integrin
      Dependent Viral Entry by Modulating the Downstream Akt-RhoA GTPase-Actin
      Rearrangement Cascade.
AB  - : While the entry of infectious bursal disease virus (IBDV) is initiated by the
      binding of the virus to the two major receptors integrin and HSP90, the signaling
      events after receptor binding and how they contribute to virus entry remain
      elusive. We show here that IBDV activates c-Src by inducing the phosphorylation
      of the Y416 residue in c-Src both in DF-1 chicken fibroblasts and in vivo in the
      bursa of Fabricius from specific-pathogen-free (SPF) chickens. Importantly,
      inactivated IBDV fails to stimulate c-Src Y416 phosphorylation, and a very
      virulent IBDV strain induces a much higher level of c-Src Y416 phosphorylation
      than does an attenuated strain. Inhibition of c-Src activation by an Src kinase
      inhibitor or expression of a c-Src dominant negative mutant results in a
      significant decrease in the internalization of IBDV but has little effect on
      virus adhesion. Furthermore, short hairpin RNA (shRNA) downregulation of
      integrin, either the alpha4 or beta1 subunit, but not HSP90 remarkably attenuates
      IBDV-induced c-Src Y416 phosphorylation, resulting in a decrease in IBDV
      internalization but not virus adhesion. Moreover, interestingly, inhibition of
      either c-Src downstream of the phosphatidylinositol 3-kinase (PI3K)/Akt-RhoA
      signaling cascade or actin rearrangement leads to a significant decrease in IBDV
      internalization irrespective of the IBDV-induced high levels of c-Src
      phosphorylation. Cumulatively, our results suggest a novel feed-forward model
      whereby IBDV activates c-Src for benefiting its cell entry via an integrin
      mediated pathway by the activation of downstream PI3K/Akt-RhoA signaling and
      cytoskeleton actin rearrangement. IMPORTANCE: While IBDV-caused immunosuppression
      is highly related to viral invasion, the molecular basis of the cellular entry of
      IBDV remains elusive. In this study, we demonstrate that IBDV activates c-Src by
      inducing the phosphorylation of the Y416 residue in c-Src to promote virus
      internalization but not virus adhesion. The ability to induce the level of c-Src
      Y416 phosphorylation correlates with the pathogenicity of an IBDV strain. IBDV
      induced c-Src Y416 activation is alpha4beta1 integrin but not HSP90 dependent and
      involves the activation of the downstream PI3K/Akt-RhoA GTPase-actin
      rearrangement cascade. Thus, our findings provide new insights into the IBDV
      infection process and the potential for c-Src as a candidate target for the
      development of IBDV therapeutic drugs.

PMID- 27881657
TI  - The Crystal Structure of the Fifth Scavenger Receptor Cysteine-Rich Domain of
      Porcine CD163 Reveals an Important Residue Involved in Porcine Reproductive and
      Respiratory Syndrome Virus Infection.
AB  - : Porcine reproductive and respiratory syndrome (PRRS) has become an economically
      critical factor in swine industry since its worldwide spread in the 1990s.
      Infection by its causative agent, PRRS virus (PRRSV), was proven to be mediated
      by an indispensable receptor, porcine CD163 (pCD163), and the fifth scavenger
      receptor cysteine-rich domain (SRCR5) is essential for virus infection. However,
      the structural details and specific residues of pCD163 SRCR5 involved in
      infection have not been defined yet. In this study, we prepared recombinant
      pCD163 SRCR5 in Drosophila melanogaster Schneider 2 (S2) cells and determined its
      crystal structure at a high resolution of 2.0 A. This structure includes a
      markedly long loop region and shows a special electrostatic potential, and these
      are significantly different from those of other members of the scavenger receptor
      cysteine-rich superfamily (SRCR-SF). Subsequently, we carried out structure-based
      mutational studies to identify that the arginine residue at position 561 (Arg561)
      in the long loop region is important for PRRSV infection. Further, we showed
      Arg561 probably takes effect on the binding of pCD163 to PRRSV during virus
      invasion. Altogether the current work provides the first view of the CD163 SRCR
      domain, expands our knowledge of the invasion mechanism of PRRSV, and supports a
      molecular basis for prevention and control of the virus. IMPORTANCE: PRRS has
      caused huge economic losses to pig farming. The syndrome is caused by PRRSV, and
      PRRSV infection has been shown to be mediated by host cell surface receptors. One
      of them, pCD163, is especially indispensable, and its SRCR5 domain has been
      further demonstrated to play a significant role in virus infection. However, its
      structural details and the residues involved in infection are unknown. In this
      study, we determined the crystal structure of pCD163 SRCR5 and then carried out
      site-directed mutational studies based on the crystal structure to elucidate
      which residue is important. Our work not only provides structural information on
      the CD163 SRCR domain for the first time but also indicates the molecular
      mechanism of PRRSV infection and lays a foundation for future applications in
      prevention and control of PRRS.

PMID- 27881658
TI  - Porcine Reproductive and Respiratory Syndrome Virus Antagonizes JAK/STAT3
      Signaling via nsp5, Which Induces STAT3 Degradation.
AB  - : Signal transducer and activator of transcription 3 (STAT3) is a pleiotropic
      signaling mediator of many cytokines, including interleukin-6 (IL-6) and IL-10.
      STAT3 is known to play critical roles in cell growth, proliferation,
      differentiation, immunity and inflammatory responses. The objective of this study
      was to determine the effect of porcine reproductive and respiratory syndrome
      virus (PRRSV) infection on the STAT3 signaling since PRRSV induces a weak
      protective immune response in host animals. We report here that PRRSV infection
      of MARC-145 cells and primary porcine pulmonary alveolar macrophages led to
      significant reduction of STAT3 protein level. Several strains of both PRRSV type
      1 and type 2 led to a similar reduction of STAT3 protein level but had a minimal
      effect on its transcripts. The PRRSV-mediated STAT3 reduction was in a dose
      dependent manner as the STAT3 level decreased, along with incremental amounts of
      PRRSV inocula. Further study showed that nonstructural protein 5 (nsp5) of PRRSV
      induced the STAT3 degradation by increasing its polyubiquitination level and
      shortening its half-life from 24 h to ~3.5 h. The C-terminal domain of nsp5 was
      shown to be required for the STAT3 degradation. Moreover, the STAT3 signaling in
      the cells transfected with nsp5 plasmid was significantly inhibited. These
      results indicate that PRRSV antagonizes the STAT3 signaling by accelerating STAT3
      degradation via the ubiquitin-proteasomal pathway. This study provides insight
      into the PRRSV interference with the JAK/STAT3 signaling, leading to perturbation
      of the host innate and adaptive immune responses. IMPORTANCE: The typical
      features of immune responses in PRRSV-infected pigs are delayed onset and low
      levels of virus neutralizing antibodies, as well as weak cell-mediated immunity.
      Lymphocyte development and differentiation rely on cytokines, many of which
      signal through the JAK/STAT signaling pathway to exert their biological effects.
      Here, we discovered that PRRSV antagonizes the JAK/STAT3 signaling by inducing
      degradation of STAT3, a master transcription activator involved in multiple
      cellular processes and the host immune responses. The nsp5 protein of PRRSV is
      responsible for the accelerated STAT3 degradation. The PRRSV-mediated
      antagonizing STAT3 could lead to suppression of a broad spectrum of cytokines and
      growth factors to allow virus replication and spread in host animals. This may be
      one of the reasons for the PRRSV interference with the innate immunity and its
      poor elicitation of protective immunity. This finding provides insight into PRRSV
      pathogenesis and its interference with the host immune responses.

PMID- 27881660
TI  - The Norovirus NS3 Protein Is a Dynamic Lipid- and Microtubule-Associated Protein
      Involved in Viral RNA Replication.
AB  - : Norovirus (NoV) infections are a significant health burden to society, yet the
      lack of reliable tissue culture systems has hampered the development of
      appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived
      from murine NoV (MNV), is intimately associated with the MNV replication complex
      and the viral replication intermediate double-stranded RNA (dsRNA). We observed
      that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus
      (NV) induced the formation of distinct vesicle-like structures that did not
      colocalize with any particular protein markers to cellular organelles but
      localized to cellular membranes, in particular those with a high cholesterol
      content. Both proteins also showed some degree of colocalization with the
      cytoskeleton marker beta-tubulin. Although the distribution of MNV and NV NS3s
      were similar, NV NS3 displayed a higher level of colocalization with the Golgi
      apparatus and the endoplasmic reticulum (ER). However, we observed that although
      both proteins colocalized in membranes counterstained with filipin, an indicator
      of cholesterol content, MNV NS3 displayed a greater association with flotillin
      and stomatin, proteins known to associate with sphingolipid- and cholesterol-rich
      microdomains. Utilizing time-lapse epifluorescence microscopy, we observed that
      the membrane-derived vesicular structures induced by MNV NS3 were highly motile
      and dynamic in nature, and their movement was dependent on intact microtubules.
      These results begin to interrogate the functions of NoV proteins during virus
      replication and highlight the conserved properties of the NoV NS3 proteins among
      the seven Norovirus genogroups. IMPORTANCE: Many mechanisms involved in the
      replication of norovirus still remain unclear, including the role for the NS3
      protein, one of seven nonstructural viral proteins, which remains to be
      elucidated. This study reveals that murine norovirus (MNV) NS3 is intimately
      associated with the viral replication complex and dsRNA. We observed that the NS3
      proteins of both MNV and Norwalk virus (NV) induce prominent vesicular structures
      and that this formation is dependent on microtubules and cellular cholesterol.
      Thus, this study contributes to our understanding of protein function within
      different Norovirus genogroups and expands a growing knowledge base on the
      interaction between positive-strand RNA [(+)RNA] viruses and cellular membranes
      that contribute to the biogenesis of virus-induced membrane organelles. This
      study contributes to our understanding of viral protein function and the ability
      of a viral protein to recruit specific cellular organelles and lipids that enable
      replication.

PMID- 27881659
TI  - Glycosylphosphatidylinositol-Anchored Anti-HIV scFv Efficiently Protects CD4 T
      Cells from HIV-1 Infection and Deletion in hu-PBL Mice.
AB  - : Despite success in viral inhibition and CD4 T cell recovery by highly active
      antiretroviral treatment (HAART), HIV-1 is still not curable due to the
      persistence of the HIV-1 reservoir during treatment. One patient with acute
      myeloid leukemia who received allogeneic hematopoietic stem cell transplantation
      from a homozygous CCR5 Delta32 donor has had no detectable viremia for 9 years
      after HAART cessation. This case has inspired a field of HIV-1 cure research
      focusing on engineering HIV-1 resistance in permissive cells. Here, we employed a
      glycosylphosphatidylinositol (GPI)-scFv X5 approach to confer resistance of human
      primary CD4 T cells to HIV-1. We showed that primary CD4 T cells expressing GPI
      scFv X5 were resistant to CCR5 (R5)-, CXCR4 (X4)-, and dual-tropic HIV-1 and had
      a survival advantage compared to control cells ex vivo In a hu-PBL mouse study,
      GPI-scFv X5-transduced CD4 T cells were selected in peripheral blood and lymphoid
      tissues upon HIV-1 infection. Finally, GPI-scFv X5-transduced CD4 T cells, after
      being cotransfused with HIV-infected cells, showed significantly reduced viral
      loads and viral RNA copy numbers relative to CD4 cells in hu-PBL mice compared to
      mice with GPI-scFv AB65-transduced CD4 T cells. We conclude that GPI-scFv X5
      modified CD4 T cells could potentially be used as a genetic intervention against
      both R5- and X4-tropic HIV-1 infections. IMPORTANCE: Blocking of HIV-1 entry is
      one of most promising approaches for therapy. Genetic disruption of the HIV-1
      coreceptor CCR5 by nucleases in T cells is under 2 clinical trials and leads to
      reduced viremia in patients. However, the emergence of viruses using the CXCR4
      coreceptor is a concern for therapies applying single-coreceptor disruption.
      Here, we report that HIV-1-permissive CD4 T cells engineered with GPI-scFv X5 are
      resistant to R5-, X4-, or dual-tropic virus infection ex vivo In a preclinical
      study using hu-PBL mice, we show that CD4 T cells were protected and that GPI
      scFv X5-transduced cells were selected in HIV-1-infected animals. Moreover, we
      show that GPI-scFv X5-transduced CD4 T cells exerted a negative effect on virus
      replication in vivo We conclude that GPI-scFv X5-modified CD4 T cells could
      potentially be used as a genetic intervention against both R5- and X4-tropic HIV
      1 infections.

PMID- 27881661
TI  - Par3 integrates Tiam1 and phosphatidylinositol 3-kinase signaling to change
      apical membrane identity.
AB  - Pathogens can alter epithelial polarity by recruiting polarity proteins to the
      apical membrane, but how a change in protein localization is linked to polarity
      disruption is not clear. In this study, we used chemically induced dimerization
      to rapidly relocalize proteins from the cytosol to the apical surface. We
      demonstrate that forced apical localization of Par3, which is normally restricted
      to tight junctions, is sufficient to alter apical membrane identity through its
      interactions with phosphatidylinositol 3-kinase (PI3K) and the Rac1 guanine
      nucleotide exchange factor Tiam1. We further show that PI3K activity is required
      upstream of Rac1, and that simultaneously targeting PI3K and Tiam1 to the apical
      membrane has a synergistic effect on membrane remodeling. Thus, Par3 coordinates
      the action of PI3K and Tiam1 to define membrane identity, revealing a signaling
      mechanism that can be exploited by human mucosal pathogens.

PMID- 27881662
TI  - The polycystins are modulated by cellular oxygen-sensing pathways and regulate
      mitochondrial function.
AB  - Autosomal dominant polycystic kidney disease is caused by mutations in the genes
      encoding polycystin-1 (PC1) and polycystin-2 (PC2), which form an ion channel
      complex that may mediate ciliary sensory processes and regulate endoplasmic
      reticulum (ER) Ca2+ release. Loss of PC1 expression profoundly alters cellular
      energy metabolism. The mechanisms that control the trafficking of PC1 and PC2, as
      well as their broader physiological roles, are poorly understood. We found that
      O2 levels regulate the subcellular localization and channel activity of the
      polycystin complex through its interaction with the O2-sensing prolyl hydroxylase
      domain containing protein EGLN3 (or PHD3), which hydroxylates PC1. Moreover,
      cells lacking PC1 expression use less O2 and show less mitochondrial Ca2+ uptake
      in response to bradykinin-induced ER Ca2+ release, indicating that PC1 can
      modulate mitochondrial function. These data suggest a novel role for the
      polycystins in sensing and responding to cellular O2 levels.

PMID- 27881663
TI  - Periodic actin structures in neuronal axons are required to maintain
      microtubules.
AB  - Axons are cable-like neuronal processes wiring the nervous system. They contain
      parallel bundles of microtubules as structural backbones, surrounded by regularly
      spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an
      evolutionarily conserved, ubiquitous, highly ordered feature of axons, the
      function of PMS is unknown. Here we studied PMS abundance, organization, and
      function, combining versatile Drosophila genetics with superresolution microscopy
      and various functional readouts. Analyses with 11 actin regulators and three
      actin-targeting drugs suggest that PMS contains short actin filaments that are
      depolymerization resistant and sensitive to spectrin, adducin, and nucleator
      deficiency, consistent with microscopy-derived models proposing PMS as
      specialized cortical actin. Upon actin removal, we observed gaps in microtubule
      bundles, reduced microtubule polymerization, and reduced axon numbers, suggesting
      a role of PMS in microtubule organization. These effects become strongly enhanced
      when carried out in neurons lacking the microtubule-stabilizing protein Short
      stop (Shot). Combining the aforementioned actin manipulations with Shot
      deficiency revealed a close correlation between PMS abundance and microtubule
      regulation, consistent with a model in which PMS-dependent microtubule
      polymerization contributes to their maintenance in axons. We discuss potential
      implications of this novel PMS function along axon shafts for axon maintenance
      and regeneration.

PMID- 27881665
TI  - Local pulsatile contractions are an intrinsic property of the myosin 2A motor in
      the cortical cytoskeleton of adherent cells.
AB  - The role of nonmuscle myosin 2 (NM2) pulsatile dynamics in generating contractile
      forces required for developmental morphogenesis has been characterized, but
      whether these pulsatile contractions are an intrinsic property of all actomyosin
      networks is not known. Here we used live-cell fluorescence imaging to show that
      transient, local assembly of NM2A "pulses" occurs in the cortical cytoskeleton of
      single adherent cells of mesenchymal, epithelial, and sarcoma origin, independent
      of developmental signaling cues and cell-cell or cell-ECM interactions. We show
      that pulses in the cortical cytoskeleton require Rho-associated kinase- or myosin
      light chain kinase (MLCK) activity, increases in cytosolic calcium, and NM2
      ATPase activity. Surprisingly, we find that cortical cytoskeleton pulses
      specifically require the head domain of NM2A, as they do not occur with either
      NM2B or a 2B-head-2A-tail chimera. Our results thus suggest that pulsatile
      contractions in the cortical cytoskeleton are an intrinsic property of the NM2A
      motor that may mediate its role in homeostatic maintenance of tension in the
      cortical cytoskeleton of adherent cells.

PMID- 27881664
TI  - Lipid disequilibrium disrupts ER proteostasis by impairing ERAD substrate glycan
      trimming and dislocation.
AB  - The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment
      of the secretory proteome. Proteins that fail to achieve their native
      conformation are retained in the ER and targeted for clearance by ER-associated
      degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent
      delivery of substrates to the 26S proteasome for proteolysis. Recent findings
      indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a
      fatty acid analogue, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a
      role for LDs in ERAD. However, whether LDs are involved in the ERAD process
      remains an outstanding question. Using chemical and genetic approaches to disrupt
      diacylglycerol acyltransferase (DGAT)-dependent LD biogenesis, we provide
      evidence that LDs are dispensable for ERAD in mammalian cells. Instead, our
      results suggest that triacsin C causes global alterations in the cellular lipid
      landscape that disrupt ER proteostasis by interfering with the glycan trimming
      and dislocation steps of ERAD. Prolonged triacsin C treatment activates both the
      IRE1 and PERK branches of the unfolded protein response and ultimately leads to
      IRE1-dependent cell death. These findings identify an intimate relationship
      between fatty acid metabolism and ER proteostasis that influences cell viability.

PMID- 27881668
TI  - Restoration of thermoregulation after exercise.
AB  - Performing exercise, especially in hot conditions, can heat the body, causing
      significant increases in internal body temperature. To offset this increase,
      powerful and highly developed autonomic thermoregulatory responses (i.e., skin
      blood flow and sweating) are activated to enhance whole body heat loss; a
      response mediated by temperature-sensitive receptors in both the skin and the
      internal core regions of the body. Independent of thermal control of heat loss,
      nonthermal factors can have profound consequences on the body's ability to
      dissipate heat during exercise. These include the activation of the body's
      sensory receptors (i.e., baroreceptors, metaboreceptors, mechanoreceptors, etc.)
      as well as phenotypic factors such as age, sex, acclimation, fitness, and chronic
      diseases (e.g., diabetes). The influence of these factors extends into recovery
      such that marked impairments in thermoregulatory function occur, leading to
      prolonged and sustained elevations in body core temperature. Irrespective of the
      level of hyperthermia, there is a time-dependent suppression of the body's
      physiological ability to dissipate heat. This delay in the restoration of
      postexercise thermoregulation has been associated with disturbances in
      cardiovascular function which manifest most commonly as postexercise hypotension.
      This review examines the current knowledge regarding the restoration of
      thermoregulation postexercise. In addition, the factors that are thought to
      accelerate or delay the return of body core temperature to resting levels are
      highlighted with a particular emphasis on strategies to manage heat stress in
      athletic and/or occupational settings.

PMID- 27881666
TI  - How and why intralumenal membrane fragments form during vacuolar lysosome fusion.
AB  - Lysosomal membrane fusion mediates the last step of the autophagy and endocytosis
      pathways and supports organelle remodeling and biogenesis. Because fusogenic
      proteins and lipids concentrate in a ring at the vertex between apposing
      organelle membranes, the encircled area of membrane can be severed and
      internalized within the lumen as a fragment upon lipid bilayer fusion. How or why
      this intralumenal fragment forms during fusion, however, is not entirely clear.
      To better understand this process, we studied fragment formation during homotypic
      vacuolar lysosome membrane fusion in Saccharomyces cerevisiae Using cell-free
      fusion assays and light microscopy, we find that GTPase activation and trans
      SNARE complex zippering have opposing effects on fragment formation and verify
      that this affects the morphology of the fusion product and regulates transporter
      protein degradation. We show that fragment formwation is limited by stalk
      expansion, a key intermediate of the lipid bilayer fusion reaction. Using
      electron microscopy, we present images of hemifusion diaphragms that form as
      stalks expand and propose a model describing how the fusion machinery regulates
      fragment formation during lysosome fusion to control morphology and protein
      lifetimes.

PMID- 27881667
TI  - A mechanistic physicochemical model of carbon dioxide transport in blood.
AB  - : A number of mathematical models have been produced that, given the Pco2 and Po2
      of blood, will calculate the total concentrations for CO2 and O2 in blood.
      However, all these models contain at least some empirical features, and thus do
      not represent all of the underlying physicochemical processes in an entirely
      mechanistic manner. The aim of this study was to develop a physicochemical model
      of CO2 carriage by the blood to determine whether our understanding of the
      physical chemistry of the major chemical components of blood together with their
      interactions is sufficiently strong to predict the physiological properties of
      CO2 carriage by whole blood. Standard values are used for the ionic composition
      of the blood, the plasma albumin concentration, and the hemoglobin concentration.
      All Km values required for the model are taken from the literature. The
      distribution of bicarbonate, chloride, and H+ ions across the red blood cell
      membrane follows that of a Gibbs-Donnan equilibrium. The system of equations that
      results is solved numerically using constraints for mass balance and
      electroneutrality. The model reproduces the phenomena associated with CO2
      carriage, including the magnitude of the Haldane effect, very well. The
      structural nature of the model allows various hypothetical scenarios to be
      explored. Here we examine the effects of 1) removing the ability of hemoglobin to
      form carbamino compounds; 2) allowing a degree of Cl- binding to deoxygenated
      hemoglobin; and 3) removing the chloride (Hamburger) shift. The insights gained
      could not have been obtained from empirical models. NEW & NOTEWORTHY: This study
      is the first to incorporate a mechanistic model of chloride-bicarbonate exchange
      between the erythrocyte and plasma into a full physicochemical model of the
      carriage of carbon dioxide in blood. The mechanistic nature of the model allowed
      a theoretical study of the quantitative significance for carbon dioxide transport
      of carbamino compound formation; the putative binding of chloride to deoxygenated
      hemoglobin, and the chloride (Hamburger) shift.

PMID- 27881669
TI  - Aerobic exercise in humans mobilizes HSCs in an intensity-dependent manner.
AB  - : Hematopoietic stem and progenitor cells are necessary to maintain, repair, and
      reconstitute the hematopoietic blood cell system. Mobilization of these cells
      from bone marrow to blood can be greatly increased under certain conditions, one
      such being exercise. The purpose of this study was to identify the importance of
      exercise intensity in hematopoietic mobilization, to better understand the
      mobilization kinetics postexercise, and to determine if exercise is capable of
      mobilizing several specific populations of hematopoietic cells that have clinical
      relevance in a transplant setting. Healthy individuals were exercised on a cycle
      ergometer at 70% of their peak work rate (WRpeak) until volitional fatigue and at
      30% of their WRpeak work matched to the 70% WRpeak bout. Blood was collected
      before, immediately post, and 10, 30, and 60 min postexercise. Total blood cells,
      hematocrit, and mononuclear cells isolated by density gradient centrifugation
      were counted. Specific populations of hematopoietic stem cells were analyzed by
      flow cytometry. Mononuclear cells, CD34+, CD34+/CD38-, CD34+/CD110+, CD3
      /CD16+/CD56+, CD11c+/CD123-, and CD11c-/CD123+ cells per millilter of blood
      increased postexercise. Overall, the 70% WRpeak exercise group showed greater
      mobilization immediately postexercise, while there was no observable increase in
      mobilization in the work matched 30% WRpeak exercise group. Mobilization of
      specific populations of hematopoietic cells mirrored changes in the general
      mobilization of mononuclear cells, suggesting that exercise serves as a
      nonspecific mobilization stimulus. Evidently, higher intensity exercise is
      capable of mobilizing hematopoietic cells to a large extent and immediately
      postexercise is an ideal time point for their collection. NEW & NOTEWORTHY: Here
      we demonstrate for the first time that mobilization of hematopoietic stem cells
      (HSCs) through exercise is intensity dependent, with the greatest mobilization
      occurring immediately after high-intensity exercise. As well, we show that
      exercise is a general stimulus for mobilization: increases in specific HSC
      populations are reliant on general mononuclear cell mobilization. Finally, we
      demonstrate no differences in mobilization between groups with different aerobic
      fitness.

PMID- 27881670
TI  - The effect of alternate-day caloric restriction on the metabolic consequences of
      8 days of bed rest in healthy lean men: a randomized trial.
AB  - : Physical activity and alternate-day fasting/caloric restriction may both
      ameliorate aspects of the metabolic syndrome, such as insulin resistance,
      visceral fat mass accumulation, and cognitive impairment by overlapping
      mechanisms. The purpose of this study was to test the hypothesis that alternate
      day caloric restriction (ADCR) with overall energy balance would reduce insulin
      resistance and accumulation of visceral fat, in addition to improving cognitive
      functions, after 8 consecutive days in bed. Healthy, lean men (n = 20) were
      randomized to 1) 8 days of bed rest with three daily isoenergetic meals (control
      group, n = 10); and 2) 8 days of bed rest with 25% of total energy requirements
      every other day and 175% of total energy requirements every other day (ADCR
      group). Oral glucose tolerance testing, dual-energy X-ray absorptiometry (DXA)
      scans, magnetic resonance imaging of the abdomen and brain, Vo2max, and tests for
      cognitive function were performed before and after bed rest. In addition, daily
      fasting blood samples and 24-h glucose profiles by continuous glucose monitoring
      system were assessed during the 8 days of bed rest period. Bed rest induced
      insulin resistance, visceral fat accumulation, and worsening of mood. No positive
      effects emerged from ADCR on these negative health outcomes. Compared with the
      control group, ADCR was associated with improved and steadier glycemic control on
      fasting days and higher glycemic fluctuation and indexes of insulin resistance on
      overeating days. In contrast to our hypothesis, the metabolic impairment induced
      by 8 days of bed rest was not counteracted by ADCR with overall energy balance.
      NEW & NOTEWORTHY: Alternate-day caloric restriction without overall energy
      reduction does not ameliorate the metabolic impairment induced in lean men by 8
      days of bed rest.

PMID- 27881671
TI  - Sex-based difference in Achilles peritendinous levels of matrix
      metalloproteinases and growth factors after acute resistance exercise.
AB  - Several recent investigations have demonstrated that the ability of various
      tendons to alter structural and functional properties in response to exercise are
      muted in women compared with men. We hypothesize that this disparity between men
      and women may be due to a reduced tendon production of key mediators of tendon
      extracellular matrix (ECM) remodeling in response to mechanical loading, e.g.,
      exercise. Using microdialysis before and after an acute bout of resistance
      exercise, we evaluated Achilles peritendinous levels of insulin-like growth
      factor-1 (IGF-1) and interleukin-6 (IL-6), which have both been shown to increase
      tendon collagen synthesis. Additionally, the matrix remodeling enzymes matrix
      metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-1
      (TIMP-1) were also evaluated. IGF-1 levels were elevated (P < 0.05) to a similar
      extent in men and women after 3 h of exercise but remained elevated at 4 h in
      only women. IL-6 levels were ~4-fold greater after exercise in both men and women
      (P < 0.05). MMP-2 levels increased to a similar extent (~2-3-fold) in men and
      women (P < 0.05). In contrast, MMP-9 increased with exercise but only in men (P <
      0.05). Last, TIMP-1 levels also increased (P < 0.05) with exercise in men and
      women but the increase was more prolonged in women. In conclusion, we observed
      modest sex differences in tendon release of MMP-9, TIMP-1, and IGF-1 after acute
      resistance exercise. If such differences persist throughout a chronic exercise
      training, they may contribute to the reduced ability of women to adapt to
      exercise compared with men.NEW & NOTEWORTHY In this investigation we utilized
      microdialysis of the peritendinous Achilles to evaluate potential differences
      between men and women in tendon production of key regulators of extracellular
      matrix remodeling. We demonstrate that a modest sex-specific difference exists in
      peritendinous levels of several key extracellular matrix modulators after an
      acute bout of resistance exercise.

PMID- 27881672
TI  - Mineralocorticoid Receptor Deficiency in Macrophages Inhibits Atherosclerosis by
      Affecting Foam Cell Formation and Efferocytosis.
AB  - Mineralocorticoid receptor (MR) has been considered as a potential target for
      treating atherosclerosis. However, the cellular and molecular mechanisms are not
      completely understood. We aim to explore the functions and mechanisms of
      macrophage MR in atherosclerosis. Atherosclerosis-susceptible LDLRKO chimeric
      mice with bone marrow cells from floxed control mice or from myeloid MR knock-out
      (MRKO) mice were generated and fed with high cholesterol diet. Oil red O staining
      showed that MRKO decreased atherosclerotic lesion area in LDLRKO mice. In another
      mouse model of atherosclerosis, MRKO/APOEKO mice and floxed control/APOEKO mice
      were generated and treated with angiotensin II. Similarly, MRKO inhibited the
      atherosclerotic lesion area in APOEKO mice. Histological analysis showed that
      MRKO increased collagen coverage and decreased necrosis and macrophage
      accumulation in the lesions. In vitro results demonstrated that MRKO suppressed
      macrophage foam cell formation and up-regulated the expression of genes involved
      in cholesterol efflux. Furthermore, MRKO decreased accumulation of apoptotic
      cells and increased effective efferocytosis in atherosclerotic lesions. In vitro
      study further revealed that MRKO increased the phagocytic index of macrophages
      without affecting their apoptosis. In conclusion, MRKO reduces high cholesterol-
      or angiotensin II-induced atherosclerosis and favorably changes plaque
      composition, likely improving plaque stability. Mechanistically, MR deficiency
      suppresses macrophage foam cell formation and up-regulates expression of genes
      related to cholesterol efflux, as well as increases effective efferocytosis and
      phagocytic capacity of macrophages.

PMID- 27881673
TI  - Sortilin 1 Modulates Hepatic Cholesterol Lipotoxicity in Mice via Functional
      Interaction with Liver Carboxylesterase 1.
AB  - The liver plays a key role in cholesterol metabolism. Impaired hepatic
      cholesterol homeostasis causes intracellular free cholesterol accumulation and
      hepatocyte injury. Sortilin 1 (SORT1) is a lysosomal trafficking receptor that
      was identified by genome-wide association studies (GWAS) as a novel regulator of
      cholesterol metabolism in humans. Here we report that SORT1 deficiency protected
      against cholesterol accumulation-induced liver injury and inflammation in mice.
      Using an LC-MS/MS-based proteomics approach, we identified liver carboxylesterase
      1 (CES1) as a novel SORT1-interacting protein. Mechanistic studies further showed
      that SORT1 may regulate CES1 lysosomal targeting and degradation and that SORT1
      deficiency resulted in higher liver CES1 protein abundance. Previous studies have
      established an important role of hepatic CES1 in promoting intracellular
      cholesterol mobilization, cholesterol efflux, and bile acid synthesis.
      Consistently, high cholesterol atherogenic diet-challenged Sort1 knock-out mice
      showed less hepatic free cholesterol accumulation, increased bile acid synthesis,
      decreased biliary cholesterol secretion, and the absence of gallstone formation.
      SORT1 deficiency did not alter hepatic ceramide and fatty acid metabolism in high
      cholesterol atherogenic diet-fed mice. Finally, knockdown of liver CES1 in mice
      markedly increased the susceptibility to high cholesterol diet-induced liver
      injury and abolished the protective effect against cholesterol lipotoxicity in
      Sort1 knock-out mice. In summary, this study identified a novel SORT1-CES1 axis
      that regulates cholesterol-induced liver injury, which provides novel insights
      that improve our current understanding of the molecular links between SORT1 and
      cholesterol metabolism. This study further suggests that therapeutic inhibition
      of SORT1 may be beneficial in improving hepatic cholesterol homeostasis in
      metabolic and inflammatory liver diseases.

PMID- 27881674
TI  - A Gastrointestinal Calpain Complex, G-calpain, Is a Heterodimer of CAPN8 and
      CAPN9 Calpain Isoforms, Which Play Catalytic and Regulatory Roles, Respectively.
AB  - Calpains (CAPN) are a family of Ca2+-dependent cysteine proteases that regulate
      various cellular functions by cleaving diverse substrates. Of the 15 mammalian
      calpains, CAPN8 and CAPN9 are two that are expressed predominantly in the
      gastrointestinal tract, where they interact to form a protease complex, termed G
      calpain. However, because native G-calpain exhibits a highly restricted
      expression pattern, it has never been purified, and the interactions between
      CAPN8 and CAPN9 have not been characterized. Here, we clarified the molecular
      nature of G-calpain by using recombinant proteins and transgenic mice expressing
      FLAG-tagged CAPN8 (CAPN8-FLAG). Recombinant mouse CAPN8 and CAPN9 co-expressed in
      eukaryotic expression systems exhibited the same mobility as native mouse G
      calpain in Blue Native-PAGE gels, and CAPN8-FLAG immunoprecipitation from stomach
      homogenates of the transgenic mice showed that CAPN9 was the only protein that
      associated with CAPN8-FLAG. These results indicated that G-calpain is a
      heterodimer of CAPN8 and CAPN9. In addition, active recombinant G-calpain was
      expressed and purified using an in vitro translation system, and the purified
      protease exhibited enzymatic properties that were comparable with that of calpain
      2. We found that an active-site mutant of CAPN8, but not CAPN9, compromised G
      calpain's substrate cleavage activity, and that the N-terminal helix region of
      CAPN8 and the C-terminal EF-hands of CAPN8 and CAPN9 were involved in CAPN8/9
      dimerization. Furthermore, CAPN8 protein in Capn9-/- mice was almost completely
      lost, whereas CAPN9 was only partially lost in Capn8-/- mice. Collectively, these
      results demonstrated that CAPN8 and CAPN9 function as catalytic and chaperone
      like subunits, respectively, in G-calpain.

PMID- 27881675
TI  - The Intestinal Copper Exporter CUA-1 Is Required for Systemic Copper Homeostasis
      in Caenorhabditis elegans.
AB  - Copper plays key catalytic and regulatory roles in biochemical processes
      essential for normal growth, development, and health. Defects in copper
      metabolism cause Menkes and Wilson's disease, myeloneuropathy, and cardiovascular
      disease and are associated with other pathophysiological states. Consequently, it
      is critical to understand the mechanisms by which organisms control the
      acquisition, distribution, and utilization of copper. The intestinal enterocyte
      is a key regulatory point for copper absorption into the body; however, the
      mechanisms by which intestinal cells transport copper to maintain organismal
      copper homeostasis are poorly understood. Here, we identify a mechanism by which
      organismal copper homeostasis is maintained by intestinal copper exporter
      trafficking that is coordinated with extraintestinal copper levels in
      Caenorhabditis elegans Specifically, we show that CUA-1, the C. elegans homolog
      of ATP7A/B, localizes to lysosome-like organelles (gut granules) in the intestine
      under copper overload conditions for copper detoxification, whereas copper
      deficiency results in a redistribution of CUA-1 to basolateral membranes for
      copper efflux to peripheral tissues. Worms defective in gut granule biogenesis
      exhibit defects in copper sequestration and increased susceptibility to toxic
      copper levels. Interestingly, however, a splice isoform CUA-1.2 that lacks a
      portion of the N-terminal domain is targeted constitutively to the basolateral
      membrane irrespective of dietary copper concentration. Our studies establish that
      CUA-1 is a key intestinal copper exporter and that its trafficking is regulated
      to maintain systemic copper homeostasis. C. elegans could therefore be exploited
      as a whole-animal model system to study regulation of intra- and intercellular
      copper trafficking pathways.

PMID- 27881677
TI  - Basigin Interacts with Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 as a
      Second Erythrocyte Receptor to Promote Parasite Growth.
AB  - Elucidating the molecular mechanisms of the host-parasite interaction during red
      cell invasion by Plasmodium is important for developing newer antimalarial
      therapeutics. Recently, we have characterized a Plasmodium vivax tryptophan-rich
      antigen PvTRAg38, which is expressed by its merozoites, binds to host
      erythrocytes, and interferes with parasite growth. Interaction of this parasite
      ligand with the host erythrocyte occurs through its two regions present at amino
      acid positions 167-178 (P2) and 197-208 (P4). Each region recognizes its own
      erythrocyte receptor. Previously, we identified band 3 as the chymotrypsin
      sensitive erythrocyte receptor for the P4 region, but the other receptor, binding
      to P2 region, remained unknown. Here, we have identified basigin as the second
      erythrocyte receptor for PvTRAg38, which is resistant to chymotrypsin. The
      specificity of interaction between PvTRAg38 and basigin was confirmed by direct
      interaction where basigin was specifically recognized by P2 and not by the P4
      region of this parasite ligand. Interaction between P2 and basigin is stabilized
      through multiple amino acid residues, but Gly-171 and Leu-175 of P2 were more
      critical. These two amino acids were also critical for parasite growth. Synthetic
      peptides P2 and P4 of PvTRAg38 interfered with the parasite growth independently
      but had an additive effect if combined together indicating involvement of both
      the receptors during red cell invasion. In conclusion, PvTRAg38 binds to two
      erythrocyte receptors basigin and band 3 through P2 and P4 regions, respectively,
      to facilitate parasite growth. This advancement in our knowledge on molecular
      mechanisms of host-parasite interaction can be exploited to develop therapeutics
      against P. vivax malaria.

PMID- 27881676
TI  - Cytoplasmic Localization of Proline, Glutamic Acid, Leucine-rich Protein 1
      (PELP1) Induces Breast Epithelial Cell Migration through Up-regulation of
      Inhibitor of kappaB Kinase epsilon and Inflammatory Cross-talk with Macrophages.
AB  - Cytoplasmic localization of proline, glutamic acid, leucine-rich protein 1
      (PELP1) is observed in ~40% of women with invasive breast cancer. In mouse
      models, PELP1 overexpression in the mammary gland leads to premalignant lesions
      and eventually mammary tumors. In preliminary clinical studies, cytoplasmic
      localization of PELP1 was seen in 36% of women at high risk of developing breast
      cancer. Here, we investigated whether cytoplasmic PELP1 signaling promotes breast
      cancer initiation in models of immortalized human mammary epithelial cells
      (HMECs). Global gene expression analysis was performed on HMEC lines expressing
      vector control, PELP1-wt, or mutant PELP1 in which the nuclear localization
      sequence was altered, resulting in cytoplasmic localization of PELP1 (PELP1
      cyto). Global gene expression analysis identified that PELP1-cyto expression in
      HMECs induced NF-kappaB signaling pathways. Western blotting analysis of PELP1
      cyto HMECs showed up-regulation of inhibitor of kappaB kinase epsilon
      (IKKepsilon) and increased phosphorylation of the NF-kappaB subunit RelB. To
      determine whether secreted factors produced by PELP1-cyto HMECs promote
      macrophage activation, THP-1 macrophages were treated with HMEC-conditioned
      medium (CM). PELP1-cyto CM induced changes in THP-1 gene expression as compared
      with control cell CM. Double conditioned medium (DCM) from the activated THP-1
      cells was then applied to HMECs to determine whether paracrine signaling from
      PELP1-cyto-activated macrophages could in turn promote migration of HMECs. PELP1
      cyto DCM induced robust HMEC migration, which was reduced in DCM from PELP1-cyto
      HMECs expressing IKKepsilon shRNA. Our findings suggest that cytoplasmic
      localization of PELP1 up-regulates pro-tumorigenic IKKepsilon and secreted
      inflammatory signals, which through paracrine macrophage activation regulates the
      migratory phenotype associated with breast cancer initiation.

PMID- 27881678
TI  - Evolutionary Adaptation of the Essential tRNA Methyltransferase TrmD to the
      Signaling Molecule 3',5'-cAMP in Bacteria.
AB  - The nucleotide signaling molecule 3',5'-cyclic adenosine monophosphate (3',5'
      cAMP) plays important physiological roles, ranging from carbon catabolite
      repression in bacteria to mediating the action of hormones in higher eukaryotes,
      including human. However, it remains unclear whether 3',5'-cAMP is universally
      present in the Firmicutes group of bacteria. We hypothesized that searching for
      proteins that bind 3',5'-cAMP might provide new insight into this question.
      Accordingly, we performed a genome-wide screen and identified the essential
      Staphylococcus aureus tRNA m1G37 methyltransferase enzyme TrmD, which is
      conserved in all three domains of life as a tight 3',5'-cAMP-binding protein.
      TrmD enzymes are known to use S-adenosyl-l-methionine (AdoMet) as substrate; we
      have shown that 3',5'-cAMP binds competitively with AdoMet to the S. aureus TrmD
      protein, indicating an overlapping binding site. However, the physiological
      relevance of this discovery remained unclear, as we were unable to identify a
      functional adenylate cyclase in S. aureus and only detected 2',3'-cAMP but not
      3',5'-cAMP in cellular extracts. Interestingly, TrmD proteins from Escherichia
      coli and Mycobacterium tuberculosis, organisms known to synthesize 3',5'-cAMP,
      did not bind this signaling nucleotide. Comparative bioinformatics, mutagenesis,
      and biochemical analyses revealed that the highly conserved Tyr-86 residue in E.
      coli TrmD is essential to discriminate between 3',5'-cAMP and the native
      substrate AdoMet. Combined with a phylogenetic analysis, these results suggest
      that amino acids in the substrate binding pocket of TrmD underwent an adaptive
      evolution to accommodate the emergence of adenylate cyclases and thus the
      signaling molecule 3',5'-cAMP. Altogether this further indicates that S. aureus
      does not produce 3',5'-cAMP, which would otherwise competitively inhibit an
      essential enzyme.

PMID- 27881679
TI  - The Shigella Virulence Factor IcsA Relieves N-WASP Autoinhibition by Displacing
      the Verprolin Homology/Cofilin/Acidic (VCA) Domain.
AB  - Shigella flexneri is a bacterial pathogen that invades cells of the
      gastrointestinal tract, causing severe dysentery. Shigella mediates intracellular
      motility and spreading via actin comet tail formation. This process is dependent
      on the surface-exposed, membrane-embedded virulence factor IcsA, which recruits
      the host actin regulator N-WASP. Although it is clear that Shigella requires N
      WASP for this process, the molecular details of this interaction and the
      mechanism of N-WASP activation remain poorly understood. Here, we show that co
      expression of full-length IcsA and the Shigella membrane protease IcsP yields
      highly pure IcsA passenger domain (residues 53-758). We show that IcsA is
      monomeric and describe the solution structure of the passenger domain obtained by
      small-angle X-ray scattering (SAXS) analysis. The SAXS-derived models suggest
      that IcsA has an elongated shape but, unlike most other autotransporter proteins,
      possesses a central kink revealing a distinctly curved structure. Pull-down
      experiments show direct binding of the IcsA passenger domain to both the WASP
      homology 1 (WH1) domain and the GTPase binding domain (GBD) of N-WASP and no
      binding to the verprolin homology/cofilin/acidic (VCA) region. Using fluorescence
      polarization experiments, we demonstrate that IcsA binding to the GBD region
      displaces the VCA peptide and that this effect is synergistically enhanced upon
      IcsA binding to the WH1 region. Additionally, domain mapping of the IcsA
      interaction interface reveals that different regions of IcsA bind to the WH1 and
      GBD domains of N-WASP. Taken together, our data support a model where IcsA and N
      WASP form a tight complex releasing the N-WASP VCA domain to recruit the host
      cell machinery for actin tail formation.

PMID- 27881680
TI  - Structures and Short Linear Motif of Disordered Transcription Factor Regions
      Provide Clues to the Interactome of the Cellular Hub Protein Radical-induced Cell
      Death1.
AB  - Intrinsically disordered protein regions (IDRs) lack a well defined three
      dimensional structure but often facilitate key protein functions. Some
      interactions between IDRs and folded protein domains rely on short linear motifs
      (SLiMs). These motifs are challenging to identify, but once found they can point
      to larger networks of interactions, such as with proteins that serve as hubs for
      essential cellular functions. The stress-associated plant protein radical-induced
      cell death1 (RCD1) is one such hub, interacting with many transcription factors
      via their flexible IDRs. To identify the SLiM bound by RCD1, we analyzed the IDRs
      in three protein partners, DREB2A (dehydration-responsive element-binding protein
      2A), ANAC013, and ANAC046, considering parameters such as disorder, context,
      charges, and pI. Using a combined bioinformatics and experimental approach, we
      have identified the bipartite RCD1-binding SLiM as (DE)X(1,2)(YF)X(1,4)(DE)L,
      with essential contributions from conserved aromatic, acidic, and leucine
      residues. Detailed thermodynamic analysis revealed both favorable and unfavorable
      contributions from the IDRs surrounding the SLiM to the interactions with RCD1,
      and the SLiM affinities ranged from low nanomolar to 50 times higher Kd values.
      Specifically, although the SLiM was surrounded by IDRs, individual intrinsic
      alpha-helix propensities varied as shown by CD spectroscopy. NMR spectroscopy
      further demonstrated that DREB2A underwent coupled folding and binding with alpha
      helix formation upon interaction with RCD1, whereas peptides from ANAC013 and
      ANAC046 formed different structures or were fuzzy in the complexes. These
      findings allow us to present a model of the stress-associated RCD1-transcription
      factor interactome and to contribute to the emerging understanding of the
      interactions between folded hubs and their intrinsically disordered partners.

PMID- 27881682
TI  - Stabilization of luciferase from Renilla reniformis using random mutations.
AB  - We expressed luciferase (RLuc) from Renilla reniformis in Escherichia coli RLuc
      was purified using a Ni-NTA column and subsequently characterized. It was
      unstable in acidic solutions and at 30 degrees C. To increase the stability of
      RLuc, the Rluc gene was randomly mutated using error-prone polymerase chain
      reaction. E. coli harboring the mutated gene was screened by detecting
      luminescence on a plate containing the substrate coelenterazine at 34 degrees C.
      Three mutants, i.e. N264SS287P, N178D and F116LI137V, were obtained. The
      solubilities and specific activities of these mutants were higher than those of
      the wild type. Furthermore, the N264SS287P mutant maintained stability at a
      temperature approximately 5 degrees C higher than that of the wild type, while
      denaturation of the F116LI137V mutant started at a temperature that was 5 degrees
      C lower than the wild type, and ended at a temperature that was 7 degrees C
      higher. We examined the obtained mutations using thermal shift assays and a
      computer program Coot in this study.

PMID- 27881681
TI  - A Novel Regulatory Mechanism of Type II Collagen Expression via a SOX9-dependent
      Enhancer in Intron 6.
AB  - Type II collagen alpha1 is specific for cartilaginous tissues, and mutations in
      its gene are associated with skeletal diseases. Its expression has been shown to
      be dependent on SOX9, a master transcription factor required for chondrogenesis
      that binds to an enhancer region in intron 1. However, ChIP sequencing revealed
      that SOX9 does not strongly bind to intron 1, but rather it binds to intron 6 and
      a site 30 kb upstream of the transcription start site. Here, we aimed to
      determine the role of the novel SOX9-binding site in intron 6. We prepared
      reporter constructs that contain a Col2a1 promoter, intron 1 with or without
      intron 6, and the luciferase gene. Although the reporter constructs were not
      activated by SOX9 alone, the construct that contained both introns 1 and 6 was
      activated 5-10-fold by the SOX9/SOX5 or the SOX9/SOX6 combination in transient
      transfection assays in 293T cells. This enhancement was also observed in rat
      chondrosarcoma cells that stably expressed the construct. CRISPR/Cas9-induced
      deletion of intron 6 in RCS cells revealed that a 10-bp region of intron 6 is
      necessary both for Col2a1 expression and SOX9 binding. Furthermore, SOX9, but not
      SOX5, binds to this region as demonstrated in an electrophoretic mobility shift
      assay, although both SOX9 and SOX5 bind to a larger 325-bp fragment of intron 6
      containing this small sequence. These findings suggest a novel mechanism of
      action of SOX5/6; namely, the SOX9/5/6 combination enhances Col2a1 transcription
      through a novel enhancer in intron 6 together with the enhancer in intron 1.

PMID- 27881683
TI  - Rational design of glycoengineered interferon-beta analogs with improved
      aggregation state: experimental validation.
AB  - Recombinant human interferon-beta (rhIFN-beta) used clinically has lower efficacy
      than expected due to protein instabilities such as aggregation. Increasing
      molecular stability, glycoengineering has been used to improve clinical efficacy
      for a number of therapeutics; however, often labor-intensive trail-and-error
      approaches are used to identify additional glycosylation sites. In this study two
      rhIFN-beta analogs with one additional glycosylation site, L6T and S75N,
      identified by a rational in silico approach, were characterized. These rhIFN-beta
      analogs were synthesized in parallel with a Chinese hamster ovary (CHO) codon
      optimized natural human IFN-beta (Opt-IFN-beta) and expressed in CHO cells using
      the same expression system. The molecular weights for both analogs were observed
      to be higher than Opt-IFN-beta, consistent with hyper-glycosylation. The in vitro
      biological assay showed the hyper-glycosylated analogs and the Opt-IFN-beta had
      similar activity. The aggregation studies demonstrated that both analogs had
      lower tendencies to aggregate compared to the Opt-IFN-beta. These experimental
      studies validate the in silico strategy to predict suitable glycosylation sites
      that would be glycosylated, while maintaining biological function. Moreover, this
      work describes hyper-glycosylated rhIFN-beta analogs with improved solubility
      (i.e. lower aggregation). These findings, together with the rational in silico
      design, will allow us to increase protein glycosylation with the goal to enhance
      therapeutic efficacy.

PMID- 27881684
TI  - Conformational flexibility of an anti-IL-13 DARPin?.
AB  - Designed ankyrin repeat proteins (DARPin(r)) are artificial non-immunoglobulin
      binding proteins with potential applications as therapeutic molecules. DARPin 6G9
      binds interleukin-13 with high affinity and blocks the signaling pathway and as
      such is promising for the treatment of asthma and other atopic diseases. The
      crystal structures of DARPin 6G9 in the unbound form and in complex with IL-13
      were determined at high resolution. The DARPin competes for the same epitope as
      the IL-13 receptor chain 13Ralpha1 but does not interfere with the binding of the
      other receptor chain, IL-4Ralpha. Analysis of multiple copies of the DARPin
      molecule in the crystal indicates the conformational instability in the N
      terminal cap that was predicted from molecular dynamics simulations. Comparison
      of the DARPin structures in the free state and in complex with IL-13 reveals a
      concerted movement of the ankyrin repeats upon binding resulted in the opening of
      the binding site. The induced-fit mode of binding employed by DARPin 6G9 is very
      unusual for DARPins since they were designed as particularly stable and rigid
      molecules. This finding shows that DARPins can operate by various binding
      mechanisms and suggests that some flexibility in the scaffold may be an
      advantage.

PMID- 27881685
TI  - Generation of camelid VHH bispecific constructs via in-cell intein-mediated
      protein trans-splicing.
AB  - Production of various combinations of bispecific variable domain of heavy chain
      of heavy chain-only antibody (VHH) constructs to evaluate their therapeutic
      potential usually requires several gene-engineering steps. Here, we present an
      alternative method of creating bispecific VHH constructs in vivo through protein
      trans-splicing (PTS) reaction; this method may reduce the number of gene
      manipulation steps required. As a proof-of-concept, we constructed a bispecific
      antibody (bsAb) containing an anti-epidermal growth factor receptor VHH and anti
      green fluorescent protein VHH, and we evaluated and confirmed its bispecificity.
      We also tested antibody labeling by fluorescent protein tagging using the PTS
      reaction. Compared with the conventional gene construction method, bsAb
      construction via PTS is a promising alternative approach for generating multiple
      bsAb combinations.

PMID- 27881686
TI  - In Their Own Words: Exploring Family Pathways to Housing Instability.
AB  - Housing instability threatens the health and well-being of millions of families
      across the United States, yet little is known about the characteristics or
      housing trajectories of at-risk families. To address this gap in our
      understanding of family risk for housing instability and homelessness, we
      undertook a qualitative descriptive study utilizing a convenience sample of 16
      mothers recruited from a housing service agency living in Detroit and receiving
      emergency services to avoid homelessness. Participants completed the Brief
      Patient Health Questionnaire (PHQ), then narrated their life events and reasons
      for housing instability and disclosed desired interventions for homelessness
      prevention. Data analysis reveals that women experienced high rates of previously
      undisclosed trauma, broken family relationships, early parenting
      responsibilities, social isolation, and system failures that contributed to
      recurrent episodes of housing instability. We argue that housing instability is a
      symptom of multiple chronic underlying issues that need more than a temporary
      financial patch.

PMID- 27881687
TI  - Bilateral cisternal abducens nerve involvement with ophthalmoplegic migraine.

PMID- 27881688
TI  - Is it time to rethink treatment of early psychosis?

PMID- 27881689
TI  - Acute Type A Aortic Dissection Treated Using a Tubular Stent-Graft in the
      Ascending Aorta and a Multibranched Stent-Graft in the Aortic Arch.
AB  - PURPOSE: To describe the combined use of a tubular stent-graft for the ascending
      aorta and an inner-branched arch stent-graft for patients with acute type A
      aortic dissection. TECHNIQUE: The technique to deploy these modular, custom-made
      stent-grafts is demonstrated in 2 patients with acute DeBakey type I aortic
      dissections and significant comorbidities precluding open surgery. Both emergent
      procedures were made possible by the availability of suitable devices
      manufactured for elective repair in other patients. After preliminary carotid
      subclavian bypass, a long Lunderquist guidewire was introduced from the right
      femoral artery to the left ventricle for delivery of the Zenith Ascend and Zenith
      Branched Arch Endovascular Grafts under inflow occlusion. Bridging stent-grafts
      were delivered to the innominate and left common carotid arteries to connect to
      the 2 inner branches; the left subclavian artery was occluded. Both cases were
      technically successful and resulted in exclusion of the false lumen in the
      ascending aorta. The operating and fluoroscopy times did not exceed those of
      comparable elective procedures. The patients were rapidly extubated shortly after
      the procedure and without serious immediate complications. One patient survived
      11 months with a satisfactory repair; the other succumbed to complications of
      recurrent pneumonia after 23 days. CONCLUSION: Endovascular treatment of patients
      with acute type A aortic dissection using a combination of tubular and branched
      stent-grafts in the ascending aorta is feasible and offers an alternative
      strategy to open surgery.

PMID- 27881690
TI  - Acceptability of Outpatient Ready-To-Use Food-Based Protocols in HIV-Infected
      Senegalese Children and Adolescents Within the MAGGSEN Cohort Study.
AB  - OBJECTIVES: To assess the acceptability of ready-to-use food (RUF)-based
      outpatient protocols in HIV-infected children and adolescents with severe acute
      malnutrition (SAM) and moderate acute malnutrition (MAM). METHODS: Plumpy Nut and
      Plumpy Sup were supplied every 2 weeks and prescribed by weight to SAM and MAM
      children, respectively. Forty-three children, 24 MAM and 19 SAM, were enrolled.
      Organoleptic appreciation, feeding modalities, and perceptions surrounding RUF
      were recorded at week 2. Sachets were counted to measure adherence throughout the
      study. RESULTS: Median age was 12.2 years (interquartile range: 9.3-14.8), and
      91% were on antiretroviral treatment. Overall, 80%, 76%, 68%, and 68% of children
      initially rated RUF color, taste, smell, and mouth feeling as good. However,
      feelings of disgust, refusal to eat, fragmentation of intake, self-stigma, and
      sharing within the household were commonly reported. Eighteen MAM and 7 SAM
      experienced weight recovery. Recovery duration was 54 days (31-90) in MAM versus
      114 days (69-151) in SAM children ( P = .02). Their rate of RUF consumption
      compared to amount prescribed was approximately 50% from week 2 to week 10. Nine
      failed to gain weight or consume RUF and were discontinued for clinical
      management, and 9 dropped out due to distance to the clinic. CONCLUSION: Initial
      RUF acceptability was satisfactory. More than half the children had successful
      weight recovery, although adherence to RUF prescription was suboptimal. However,
      further research is needed to propose therapeutic foods with improved
      palatability, alternative and simpler intervention design, and procedures for
      continuous and tailored psychosocial support in this vulnerable population. TRIAL
      REGISTRATION: NCT01771562 (Current Controlled Trials).

PMID- 27881691
TI  - A Mobile Application for Wound Assessment and Treatment: Findings of a User
      Trial.
AB  - The D+Wound Solution is a mobile phone application (app) that assists users in
      the assessment and treatment of the wound. The app has 6 components for
      assessment: need for debridement, infection control, revascularization, and
      exudate control; whether it is chronic; and finally, the top surface of the skin.
      These components are named D.I.R.E.C.T. The app makes you review these components
      as an algorithm to provide a reasonable solution for dressing. It is designed to
      understand the status of the wound and provide a practical treatment idea for
      wound care providers. A total of 118 nurses were divided into 2 groups,
      designated as experienced and less-experienced groups, and surveyed. Both groups
      found the app to be helpful in making a treatment plan. However, the less
      experienced group found it to be significantly more useful in assessing the wound
      ( P = .026) but difficult to understand the logic. The experienced group found
      the logic to be significantly easier to understand ( P = .018) and had
      significantly higher similarities ( P = .015) in treatment protocols compared
      with the less-experienced group. We may conclude that this app has a logical
      algorithm resembling experienced wound caregivers and is more useful in the less
      experienced group.

PMID- 27881693
TI  - Outcomes of Rivaroxaban Use in Patients With Sickle Cell Disease.

PMID- 27881694
TI  - Transdiaphragmatic pericardiectomy in dogs.
AB  - In patients with recurrent pericardial effusions, pericardiectomy is indicated.
      The purpose of this study was to describe a transdiaphragmatic approach for
      subtotal pericardiectomy in dogs and to evaluate its feasibility. In total, 20
      canine cadavers weighing less than 10 kg (group S) and 20 weighing more than 20
      kg (group L) were used. Within each group, half underwent a subphrenic
      pericardiectomy via an intercostal approach and half via a transdiaphragmatic
      approach. For each approach and within each weight group, the percentage of
      resected pericardium was calculated and compared. Additionally, a case series of
      nine consecutive client-owned dogs that underwent a transdiaphragmatic
      pericardiectomy for pericardial effusion was reported. Exposure of pericardium
      and associated phrenic nerves was excellent in cadavers and clinical patients. In
      group S, the percentage of resected pericardium was not significantly different
      between the two approaches. In group L, on the other hand, the percentage of
      resected pericardium was lower with the transdiaphragmatic approach compared with
      the intercostal approach (P=0.001). In the clinical patients, no intraoperative
      complications were encountered and no recurrence of pericardial effusion was
      seen. Subtotal pericardiectomy via a transdiaphragmatic approach is
      straightforward and a safe surgical procedure to obtain permanent pericardial
      drainage in small and large breed dogs.

PMID- 27881692
TI  - Monitoring of Urate-Lowering Therapy Among US Veterans Following the 2012
      American College of Rheumatology Guidelines for Management of Gout.
AB  - BACKGROUND: With the prevalence of and hospitalizations for gout increasing,
      optimizing care for patients with gout is imperative. The 2012 American College
      of Rheumatology gout guidelines emphasize that timely monitoring is key to
      achieving serum urate (SUA) goals. Few studies have examined this metric
      following the 2012 update, and to our knowledge, none have examined a veteran
      population. OBJECTIVE: To evaluate adherence to urate-lowering therapy (ULT)
      monitoring guidelines in a veteran population. METHODS: This is a single-center,
      multisite, retrospective chart review of US veterans receiving ULT for gout
      within the VA (Veterans Affairs) Tennessee Valley Healthcare System from January
      1, 2013, to June 30, 2015. The primary end point was percentage of patients with
      a SUA within 6 months of initial xanthine oxidase inhibitor prescription.
      Secondary end points included percentage of patients with SUA <6 mg/dL and
      percentage of patients with uptitration following SUA above goal. RESULTS: A
      total of 601 patients met inclusion criteria for the study; after application of
      exclusion criteria, 505 were analyzed. Of these, 295 patients (58%) did not have
      a SUA drawn within 6 months, and 162 patients (32%) reached the end of the study
      period without SUA measured. Of 226 patients with SUA above goal on initial
      check, 64 (28%) had timely dose adjustment, whereas 143 patients (63%) had no
      adjustment. A total of 161 patients (32%) had a SUA at goal within the study
      period. CONCLUSIONS: Rates of ULT monitoring at a major VA medical center were
      suboptimal, and improved adherence to guideline recommendations is needed.

PMID- 27881695
TI  - Application of sonoelastography for evaluating the stiffness of equine
      superficial digital flexor tendon during healing.
AB  - Sonoelastography can assess the inner stiffness of tissues. Sonoelastographic
      evaluation of injured equine superficial digital flexor tendons (SDFTs) is
      considered to be useful for assessing the stiffness of a lesion even during late
      stage rehabilitation. The purpose of this study was to investigate and compare
      the sonoelastographic appearance of injured SDFTs over time from the onset of the
      injury. Eighteen horses were classified into three groups according to the length
      of time from injury onset: group A, within two weeks after injury; group B,
      approximately five months after injury; and group C, approximately nine months
      after injury. Longitudinal and transverse images of all injured SDFTs were
      obtained using grey-scale ultrasonography and sonoelastography. Grey-scale and
      sonoelastographic images were evaluated by two observers using echogenicity
      grading and colour-grading systems, respectively. The authors evaluated the
      interobserver agreement and compared the grades among the three groups. The
      results indicated almost perfect interobserver agreement. Significant differences
      were found in the sonoelastography among the three groups, whereas no significant
      difference was found in the grey-scale ultrasonography between groups B and C.
      Sonoelastography is a feasible and useful modality to evaluate the equine injured
      SDFTs in vivo and to distinguish between them among the different phases even
      during the chronic phase.

PMID- 27881696
TI  - Preliminary survey of lamb losses (black loss) in Highland sheep flocks.

PMID- 27881697
TI  - Adult Day Services Outcomes: Delphi Review of an Integrated Participant
      Assessment System
AB  - Adult day services (ADS) aim to help elders age in place, but evidence of impact
      on participants lags behind caregiver research. To play a larger role in the
      continuum of care, ADS participant outcomes should regularly be documented with
      standard measures. We conducted a Delphi review of one integrated participant
      assessment system. Capturing physical, mental, and cognitive health indicators
      and activity engagement of typical ADS participants (i.e., frail elders eligible
      for nursing home placement), experts evaluated the system on instrument validity,
      relevance, and application. Practitioners and researchers completed multiple
      assessments of the system's instruments and alternatives. Finally, panelists
      addressed the potential benefits and challenges of system adoption by ADS
      providers. Panelists concurred that such a system would benefit individuals,
      families, and providers; concerns related to cost and staffing requirements and
      appropriateness for distinct client populations. A refined system can reveal best
      practices to enhance ADS service delivery and participant outcomes.

PMID- 27881698
TI  - Effects of Electrolyte Replacement Protocol Implementation in a Medical Intensive
      Care Unit.
AB  - PURPOSE: To evaluate the effects of electrolyte replacement protocol (ERP)
      implementation in the medical intensive care unit (MICU) setting. We hypothesized
      that a protocol would reduce the time of replacement dose administration and
      increase provider satisfaction with the process of electrolyte replacement.
      METHODS: This was a retrospective review of electronic medical record data before
      and after implementation of a standardized ERP in an 18-bed military tertiary
      care MICU. RESULTS: Median time from abnormal laboratory result to time of
      documented dose administration for potassium decreased from 180 to 98 minutes ( P
      < .01), phosphorus decreased from 190 to 135 minutes ( P < .01), calcium
      decreased from 95 to 61 minutes ( P < .01), and magnesium decreased from 155 to
      149 minutes ( P < .01). Overall, there was a significant reduction in time to
      electrolyte repletion from 146 to 98 minutes ( P < .01) for all electrolytes.
      Nursing satisfaction for autonomy, timeliness, effectiveness, and the need to
      seek orders was all improved ( P < .01), and physicians saved 4.4
      minutes/patient/day ( P = .04). CONCLUSIONS: Electrolyte replacement protocols
      can be safely implemented in the MICU and reduce the time from abnormal
      laboratory result to electrolyte replacement dose administration. They can
      improve provider satisfaction and reduce physician time with the process of
      electrolyte replacement.

PMID- 27881699
TI  - Multicenter Experience of Surgical Explantation of Carotid Stents for Recurrent
      Stenosis.
AB  - OBJECTIVE: A significant cohort of patients who have undergone carotid artery
      stenting (CAS) will have in-stent restenosis (ISR). The optimal management of
      symptomatic or severe ISR remains poorly defined. The purpose of this study was
      to describe the indications, treatment, and mid- to long-term outcomes of
      patients undergoing CAS explantation for ISR. METHODS: All patients undergoing
      internal carotid artery stent explantation with carotid artery reconstruction at
      Mayo Clinic Rochester, Dartmouth-Hitchcock Medical Center, and Beth-Israel
      Deaconess Medical Center from 2003 to 2013 were retrospectively reviewed.
      Isolated common carotid artery stents were excluded. Demographics, comorbidities,
      indications for explantation, operative details, and perioperative and
      postoperative outcomes were reviewed. RESULTS: Over the study interval, a total
      of 971 patients underwent carotid stenting across the 3 centers. Of these, 8
      patients ultimately underwent CAS explantation with carotid artery
      reconstruction. Mean age was 69 years and 5 patients were male. Index stent
      placement was for symptomatic stenosis in 4 patients, asymptomatic restenosis
      after endarterectomy in 2 patients, asymptomatic high lesion in 1 patient, and
      asymptomatic critical stenosis in 1 patient. Indications for explantation were
      symptomatic ISR in 4 patients and asymptomatic severe ISR in 4 patients. Method
      of repair was stent explantation and patch angioplasty in 5 and en bloc carotid
      resection with bypass in 3 patients. There were no perioperative neurologic
      events or cranial nerve injuries. At a mean follow-up of 38.7 months, there were
      2 late disabling ipsilateral strokes (14.4 months and 19.1 months). CONCLUSION: A
      significant cohort of patients who have undergone CAS will have ISR. Although
      excellent perioperative results after surgical explantation can be obtained, this
      patient subgroup remains at risk for late neurologic events. Appropriate patient
      selection and diligent long-term follow-up are mandated to obtain optimal
      outcomes.

PMID- 27881700
TI  - Veno-venous ECMO as a safe bridge to recovery in a patient with severe peripartum
      cardiomyopathy - learning from errors.
AB  - Peripartum cardiomyopathy (PPCM) is a rare disorder of unknown etiology and
      pathogenesis. The most important tool for diagnostic confirmation is
      transthoracic echocardiography. The recommended management of PPCM in pregnancy
      is summarized by the European Society of Cardiology Heart Failure Guidelines. Few
      data exist on the treatment of patients with fulminant PPCM and the need for
      extracorporeal membrane oxygenation (ECMO) in this context. We report on a young
      multiparous woman with cardiogenic shock caused by severe PPCM who was
      successfully, but atypically, supported with veno-venous ECMO as a bridge to
      recovery immediately after the birth of her third child.

PMID- 27881701
TI  - Externally visible thrombus partially predicts internal thrombus deposition in
      extracorporeal membrane oxygenators.
AB  - AIM: We sought to quantify the location and volume of thrombus in used hollow
      fiber membrane oxygenators and correlate the volume of thrombus with patient
      demographics, flow characteristics and anticoagulation parameters. METHODS:
      Hollow-fiber membrane oxygenators (Quadrox D, Maquet, Rastatt, Germany) were
      collected after clinical use in ECMO circuits and divided into sections. Each
      section was digitally imaged and analyzed using ImageJ software. The location and
      total volume (cm3) of thrombus was calculated for different sections. In an
      effort to predict thrombus formation, we correlated thrombus volume with possible
      aggravating and mitigating variables. RESULTS: We collected 41 oxygenators from
      27 patients. Twenty-seven (66%) were configured in the veno-venous mode and 14
      (34%) in the veno-arterial mode. The median duration of use was 131 hours
      (interquartile range 61-214 hours). Eighteen (44%) were removed when the patient
      recovered, six (15%) were removed after withdrawal of care and seventeen (41%)
      were exchanged. The median volume of thrombus was 11.4 cm3 (interquartile range
      2.2-44.5 cm3). CONCLUSIONS: A multivariable linear regression model suggested
      that the combination of median flow, configuration of ECMO and visible thrombus
      partially predicted internal thrombus volume (adjusted R2=0.39).

PMID- 27881703
TI  - Semaphorin 4C Protects against Allergic Inflammation: Requirement of Regulatory
      CD138+ Plasma Cells.
AB  - The regulatory properties of B cells have been studied in autoimmune diseases;
      however, their role in allergic diseases is poorly understood. We demonstrate
      that Semaphorin 4C (Sema4C), an axonal guidance molecule, plays a crucial role in
      B cell regulatory function. Mice deficient in Sema4C exhibited increased airway
      inflammation after allergen exposure, with massive eosinophilic lung infiltrates
      and increased Th2 cytokines. This phenotype was reproduced by mixed bone marrow
      chimeric mice with Sema4C deficient only in B cells, indicating that B
      lymphocytes were the key cells affected by the absence of Sema4C expression in
      allergic inflammation. We determined that Sema4C-deficient CD19+CD138+ cells
      exhibited decreased IL-10 and increased IL-4 expression in vivo and in vitro.
      Adoptive transfer of Sema4c-/- CD19+CD138+ cells induced marked pulmonary
      inflammation, eosinophilia, and increased bronchoalveolar lavage fluid IL-4 and
      IL-5, whereas adoptive transfer of wild-type CD19+CD138+IL-10+ cells dramatically
      decreased allergic airway inflammation in wild-type and Sema4c-/- mice. This
      study identifies a novel pathway by which Th2-mediated immune responses are
      regulated. It highlights the importance of plasma cells as regulatory cells in
      allergic inflammation and suggests that CD138+ B cells contribute to cytokine
      balance and are important for maintenance of immune homeostasis in allergic
      airways disease. Furthermore, we demonstrate that Sema4C is critical for optimal
      regulatory cytokine production in CD138+ B cells.

PMID- 27881702
TI  - Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming
      CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and
      Protection by T-Dependent Influenza Vaccine.
AB  - Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown.
      We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum
      hydroxide (Alum) adjuvant (MPL+Alum) in inducing immunity after immunization of
      CD4 knockout (CD4KO) and wild-type (WT) mice with T-dependent influenza vaccine.
      MPL+Alum adjuvant mediated IgG isotype-switched Abs, IgG-secreting cell
      responses, and protection in CD4KO mice, which were comparable to those in WT
      mice. In contrast, Alum adjuvant effects were dependent on CD4+ T cells. MPL+Alum
      adjuvant was effective in recruiting monocytes and neutrophils as well as in
      protecting macrophages from Alum-mediated cell loss at the injection site in
      CD4KO mice. MPL+Alum appeared to attenuate MPL-induced inflammatory responses in
      WT mice, likely improving the safety. Additional studies in CD4-depleted WT mice
      and MHC class II KO mice suggest that MHC class II+ APCs contribute to providing
      alternative B cell help in the CD4-deficient condition in the context of MPL+Alum
      adjuvanted vaccination.

PMID- 27881704
TI  - Generation of a Novel HLA Class I Transgenic Mouse Model Carrying a Knock-in
      Mutation at the beta2-Microglobulin Locus.
AB  - We generated a series of monochain HLA class I knock-in (KI) mouse strains, in
      which a chimeric HLA class I molecule (alpha1/alpha2 domain of HLA-A*0201, HLA
      A*0301, HLA-A*2402, or HLA-A*3101 and alpha3 domain of H-2Db) was covalently
      linked with 15 aa to human beta2-microglobulin (beta2m) and introduced into the
      endogenous mouse beta2m locus. In homozygous KI mice, mouse beta2m gene
      disruption resulted in loss of the endogenous H-2 class I molecules and reduction
      in the peripheral CD8+ T cell population that was partially restored by monochain
      HLA class I expression. A gene dosage-dependent expression of HLA, similar to
      that in human PBMCs, was detected in heterozygous and homozygous HLA KI mice.
      Upon vaccination with various virus epitopes, HLA-restricted, epitope-specific
      CTLs were induced in HLA KI mice, similar to the response in the commonly used
      HLA transgenic mice. Importantly, the CTL responses induced in heterozygous KI
      mice were similar to those in homozygous KI mice. These results suggest that
      coexpression of H-2 class I does not affect HLA-restricted CTL responses in HLA
      KI mice, which differs from the situation reported for monochain HLA Tg * beta2m
      /- mice. Furthermore, we generated double KI mice harboring two different HLA
      (HLA-A*2402 and HLA-A*0301) KI alleles, which showed a CTL response against both
      HLA-A24 and HLA-A3 epitopes when immunized with a mixture of both peptides. These
      results indicated that this HLA class I KI mouse model provides powerful research
      tools not only for the study of HLA class I-restricted CTL responses, but also
      for preclinical vaccine evaluation.

PMID- 27881706
TI  - IL1R9 Is Evolutionarily Related to IL18BP and May Function as an IL-18 Receptor.
AB  - The IL-1 families of ligands and receptors exhibit similarity of coding
      sequences, protein structures, and chromosomal positions, suggesting that they
      have arisen via duplication of ancestral genes. Within these families there is
      selectivity in ligand-receptor interactions as well as promiscuity. IL-18 and its
      receptor are members of these families. IL-18 is recognized as binding to the
      protein products of the IL18R1 and IL18RAP genes, and with high affinity to a
      separate IL-18 binding protein (IL-18BP). However, IL-18BP is anomalous, as it
      exhibits little resemblance to IL-18R proteins. Additionally, IL-18 is produced
      in the brain in medial habenula neurons, which project IL-18-containing axons to
      the interpeduncular nucleus. However, there is a lack of focal IL-18R expression
      in their terminal field. Given these anomalies, we hypothesized that another
      receptor for IL-18 may exist, and that IL18BP is evolutionarily related to this
      receptor. We examined Ensembl and National Center for Biotechnology Information
      databases to identify available IL18BP records (n = 86 species) and show through
      bioinformatics approaches that across mammalian species with IL18BP genes, IL
      18BP is consistently most similar to IL-1R9 (IL-1R accessory protein-like 2),
      another member of the IL-1R family. IL-1R9 and the related IL-1R8, but not other
      IL-1R family members, exhibit an amino acid sequence similar to binding site A of
      human and viral IL-18BPs. Conserved intron/exon boundaries, protein structure,
      and key binding site amino acids suggest that IL18BP and IL1R9 are evolutionarily
      related, and that IL-1R9 and IL-1R8 may bind IL-18.

PMID- 27881705
TI  - Essential Role of mTORC1 in Self-Renewal of Murine Alveolar Macrophages.
AB  - Alveolar macrophages (AMphi) have the capacity of local self-renewal through
      adult life; however, mechanisms that regulate AMphi self-renewal remain poorly
      understood. We found that myeloid-specific deletion of Raptor, an essential
      component of the mammalian/mechanistic target of rapamycin complex (mTORC)1,
      resulted in a marked decrease of this population of cells accompanying altered
      phenotypic features and impaired phagocytosis activity. We demonstrated further
      that Raptor/mTORC1 deficiency did not affect AMphi development, but compromised
      its proliferative activity at cell cycle entry in the steady-state as well as in
      the context of repopulation in irradiation chimeras. Mechanically, mTORC1 confers
      AMphi optimal responsiveness to GM-CSF-induced proliferation. Thus, our results
      demonstrate an essential role of mTORC1 for AMphi homeostasis by regulating
      proliferative renewal.

PMID- 27881707
TI  - A CD80-Biased CTLA4-Ig Fusion Protein with Superior In Vivo Efficacy by
      Simultaneous Engineering of Affinity, Selectivity, Stability, and FcRn Binding.
AB  - Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with
      enhanced pharmacokinetic profiles could yield improved therapies with the
      potential of higher efficacy and greater convenience to patients. In this study,
      to our knowledge, we have, for the first time, used in vitro evolution to
      simultaneously optimize CTLA4 affinity and stability. We selected for improved
      binding to both ligands, CD80 and CD86, and screened as dimeric Fc fusions
      directly in functional assays to identify variants with stronger suppression of
      in vitro T cell activation. The majority of CTLA4 molecules showing the largest
      potency gains in primary in vitro and ex vivo human cell assays, using PBMCs from
      type 1 diabetes patients, had significant improvements in CD80, but only modest
      gains in CD86 binding. We furthermore observed different potency rankings between
      our lead molecule MEDI5265, abatacept, and belatacept, depending on which type of
      APC was used, with MEDI5265 consistently being the most potent. We then created
      fusions of both stability- and potency-optimized CTLA4 moieties with human Fc
      variants conferring extended plasma t1/2 In a cynomolgus model of T cell
      dependent Ab response, the CTLA4-Ig variant MEDI5265 could be formulated at >100
      mg/ml for s.c. administration and showed superior efficacy and significantly
      prolonged serum t1/2 The combination of higher stability and potency with
      prolonged pharmacokinetics could be compatible with very infrequent, s.c. dosing
      while maintaining a similar level of immune suppression to more frequently and
      i.v. administered licensed therapies.

PMID- 27881708
TI  - IL-35 Suppresses Lipopolysaccharide-Induced Airway Eosinophilia in EBI3-Deficient
      Mice.
AB  - EBI3 functions as the subunit of immune-regulatory cytokines, such as IL-27 and
      IL-35, by pairing with p28 and p35, respectively. We treated wild-type and EBI3
      deficient mice with intratracheal administration of LPS and obtained
      bronchoalveolar lavage fluid (BALF) 24 h later. Although neutrophils were the
      predominant cells in BALF from both groups of mice, eosinophils were highly
      enriched and there was increased production of eosinophil-attracting chemokines
      CCL11 and CCL24 in BALF of EBI3-deficient mice. The bronchial epithelial cells
      and alveolar macrophages were the major producers of CCL11 and CCL24. Because no
      such increases in eosinophils were seen in BALF of p28/IL-27-deficient mice or
      WSX-1/IL-27Ralpha subunit-deficient mice upon intratracheal stimulation with LPS,
      we considered that the lack of IL-35 was responsible for the enhanced airway
      eosinophilia in EBI3-deficient mice. In vitro, IL-35 potently suppressed
      production of CCL11 and CCL24 by human lung epithelial cell lines treated with
      TNF-alpha and IL-1beta. IL-35 also suppressed phosphorylation of STAT1 and STAT3
      and induced suppressor of cytokine signaling 3. In vivo, rIL-35 dramatically
      reduced LPS-induced airway eosinophilia in EBI3-deficient mice, with concomitant
      reduction of CCL11 and CCL24, whereas neutralization of IL-35 significantly
      increased airway eosinophils in LPS-treated wild-type mice. Collectively, our
      results suggest that IL-35 negatively regulates airway eosinophilia, at least in
      part by reducing the production of CCL11 and CCL24.

PMID- 27881710
TI  - The Role of Hedonic Behavior in Reducing Perceived Risk.
AB  - Understanding how human populations naturally respond to and cope with risk is
      important for fields ranging from psychology to public health. We used
      geophysical and individual-level mobile-phone data (mobile-apps,
      telecommunications, and Web usage) of 157,358 victims of the 2013 Ya'an
      earthquake to diagnose the effects of the disaster and investigate how
      experiencing real risk (at different levels of intensity) changes behavior.
      Rather than limiting human activity, higher earthquake intensity resulted in
      graded increases in usage of communications apps (e.g., social networking,
      messaging), functional apps (e.g., informational tools), and hedonic apps (e.g.,
      music, videos, games). Combining mobile data with a field survey ( N = 2,000)
      completed 1 week after the earthquake, we use an instrumental-variable approach
      to show that only increases in hedonic behavior reduced perceived risk. Thus,
      hedonic behavior could potentially serve as a population-scale coping and
      recovery strategy that is often missing in risk management and policy
      considerations.

PMID- 27881711
TI  - Mitochondrial fusion: Reaching the end of mitofusin's tether.
AB  - In this issue, Qi et al. (2016. J. Cell Biol
      https://doi.org/10.1083/jcb.201609019) provide structural insights into the
      mechanisms of mitochondrial outer membrane fusion by investigating the structure
      of mitofusin 1 (MFN1). This work proposes a new model to explain the important
      and elusive process of MFN-mediated mitochondrial fusion.

PMID- 27881712
TI  - Astrocytic TLR4 at the crossroads of inflammation and seizure susceptibility.
AB  - Astrocytes have been implicated in epilepsy development, but their contribution
      is under debate. In this issue, Shen et al. (2016. J. Cell Biol.
      https://doi.org/10.1083/jcb.201605046) demonstrate that early postnatal
      inflammatory stimuli activate toll-like receptor 4 signaling in astrocytes and
      promote excitatory synaptogenesis, thereby increasing seizure susceptibility in
      young and adult mice.

PMID- 27881709
TI  - Relationship Between Metformin Use and Recurrence and Survival in Patients With
      Resected Stage III Colon Cancer Receiving Adjuvant Chemotherapy: Results From
      North Central Cancer Treatment Group N0147 (Alliance).
AB  - BACKGROUND: Preclinical and epidemiological data suggest that metformin might
      have antineoplastic properties against colon cancer (CC). However, the effect of
      metformin use on patient survival in stage III CC after curative resection is
      unknown. The survival outcomes were comparable regardless of the duration of
      metformin use. PATIENTS AND METHODS: Before randomization to FOLFOX (folinic
      acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with
      stage III CC enrolled in the N0147 study completed a questionnaire with
      information on diabetes mellitus (DM) and metformin use. Cox models were used to
      assess the association between metformin use and disease-free survival (DFS),
      overall survival (OS), and the time to recurrence (TTR), adjusting for clinical
      and/or pathological factors. RESULTS: Of the 1,958 patients, 1,691 (86%) reported
      no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM
      without metformin use (8%). The adjuvant treatment arms were pooled, because
      metformin use showed homogeneous effects on outcomes across the two arms. Among
      the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95%
      confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49;
      p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for
      the metformin users compared with the nonusers after adjusting for tumor and
      patient factors. The survival outcomes were comparable regardless of the duration
      of metformin use (<1, 1-5, 6-10, >=11 years) before randomization (ptrend = .64
      for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects
      were observed between metformin use and KRAS, BRAF mutation status, tumor site,
      T/N stage, gender, or age. CONCLUSIONS: Patients with stage III CC undergoing
      adjuvant chemotherapy who used metformin before the diagnosis of CC experienced
      DFS, OS, and TTR similar to those for non-DM patients and DM patients without
      metformin use. IMPLICATIONS FOR PRACTICE: The present study did not find any
      relationship between metformin use or its duration and disease-free survival,
      time to recurrence, and overall survival in a large cohort of patients with
      resected stage III colon cancer receiving adjuvant FOLFOX (folinic acid,
      fluorouracil, oxaliplatin)-based chemotherapy. This relationship was not modified
      by KRAS or BRAF mutation or DNA mismatch repair status. Metformin use did not
      increase or decrease the likelihood of chemotherapy-related grade 3 or higher
      adverse events.

PMID- 27881713
TI  - GTSE1 tunes microtubule stability for chromosome alignment and segregation by
      inhibiting the microtubule depolymerase MCAK.
AB  - The dynamic regulation of microtubules (MTs) during mitosis is critical for
      accurate chromosome segregation and genome stability. Cancer cell lines with
      hyperstabilized kinetochore MTs have increased segregation errors and elevated
      chromosomal instability (CIN), but the genetic defects responsible remain largely
      unknown. The MT depolymerase MCAK (mitotic centromere-associated kinesin) can
      influence CIN through its impact on MT stability, but how its potent activity is
      controlled in cells remains unclear. In this study, we show that GTSE1, a protein
      found overexpressed in aneuploid cancer cell lines and tumors, regulates MT
      stability during mitosis by inhibiting MCAK MT depolymerase activity. Cells
      lacking GTSE1 have defects in chromosome alignment and spindle positioning as a
      result of MT instability caused by excess MCAK activity. Reducing GTSE1 levels in
      CIN cancer cell lines reduces chromosome missegregation defects, whereas
      artificially inducing GTSE1 levels in chromosomally stable cells elevates
      chromosome missegregation and CIN. Thus, GTSE1 inhibition of MCAK activity
      regulates the balance of MT stability that determines the fidelity of chromosome
      alignment, segregation, and chromosomal stability.

PMID- 27881714
TI  - A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by
      shedding CRIPTO.
AB  - Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the
      cell membrane by GPI cleavage. In this study, we report a novel GPI-processing
      enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6
      (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell
      surface. CRIPTO, a GPI-AP, which plays critical roles in early embryonic
      development by acting as a Nodal coreceptor, is a highly sensitive substrate of
      PGAP6, whereas CRYPTIC, a close homologue of CRIPTO, is not sensitive. CRIPTO
      processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which
      is further cleaved by phospholipase D. CRIPTO shed by PGAP6 was active as a
      coreceptor in Nodal signaling, whereas cell-associated CRIPTO activity was
      reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects
      in early embryonic development, particularly in the formation of the anterior
      posterior axis, which are common features with Cripto knockout embryos. These
      results suggest PGAP6 plays a critical role in Nodal signaling modulation through
      CRIPTO shedding.

PMID- 27881715
TI  - S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1
      mediated biological functions: calcium flux and S1PR1 internalization.
AB  - HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and
      the S1P in HDL reportedly mediates several HDL-associated biological effects and
      signaling pathways. The HDL receptor, SR-BI, as well as the cell surface
      receptors for S1P (S1PRs) may be involved partially and/or completely in these
      HDL-induced processes. Here we investigate the nature of the HDL-stimulated
      interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment
      complementation assay and confocal microscopy. In both primary rat aortic
      vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles
      increased intracellular calcium concentration, which was mediated by S1PR1.
      Mechanistic studies performed in HEK293 cells showed that incubation of cells
      with HDL led to an increase in the physical interaction between the SR-BI and
      S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant
      HDL (rHDL) particles formed in vitro with S1P incorporated into the particle
      initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did
      not, suggesting that S1P transported in HDL can selectively activate S1PR1. In
      conclusion, these data suggest that S1P in HDL stimulates the transient
      interaction between SR-BI and S1PRs that can activate S1PRs and induce an
      elevation in intracellular calcium concentration.

PMID- 27881716
TI  - Influence of route of administration and lipidation of apolipoprotein A-I peptide
      on pharmacokinetics and cholesterol mobilization.
AB  - apoA-I, apoA-I mimetic peptides, and their lipid complexes or reconstituted high
      density lipoprotein (HDL) have been studied as treatments for various
      pathologies. However, consensus is lacking about the best method for
      administration, by intravenous (IV) or intraperitoneal (IP) routes, and
      formulation, as an HDL particle or in a lipid-free form. The objective of this
      study was to systematically examine peptide plasma levels, cholesterol
      mobilization, and lipoprotein remodeling in vivo following administration of
      lipid-free apoA-I peptide (22A) or phospholipid reconstituted 22A-sHDL by IV and
      IP routes. The mean circulation half-life was longer for 22A-sHDL (T1/2 = 6.27 h)
      than for free 22A (T1/2 = 3.81 h). The percentage of 22A absorbed by the vascular
      compartment after the IP dosing was ~50% for both 22A and 22A-sHDL. The strongest
      pharmacologic response came from IV injection of 22A-sHDL, specifically a 5.3
      fold transient increase in plasma-free cholesterol (FC) level compared with 1.3-
      and 1.8-fold FC increases for 22A-IV and 22A-sHDL-IP groups. Addition of either
      22A or 22A-sHDL to rat plasma caused lipoprotein remodeling and appearance of a
      lipid-poor apoA-I. Hence, both the route of administration and the formulation of
      apoA-I peptide significantly affect its pharmacokinetics and pharmacodynamics.

PMID- 27881717
TI  - Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial
      dysfunction.
AB  - 1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in
      the plasma of patients with type 2 diabetes and hereditary sensory and autonomic
      neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very
      similar, suggesting the involvement of deoxySLs in the pathology of both
      diseases. However, very little is known about the biology of these lipids and the
      underlying pathomechanism. We synthesized an alkyne analog of 1-deoxysphinganine
      (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and
      localization of deoxySLs. Our results indicate that the metabolism of these
      lipids is restricted to only some lipid species and that they are not converted
      to canonical sphingolipids or fatty acids. Furthermore, exogenously added alkyne
      doxSA [(2S,3R)-2-aminooctadec-17-yn-3-ol] localized to mitochondria, causing
      mitochondrial fragmentation and dysfunction. The induced mitochondrial toxicity
      was also shown for natural doxSA, but not for sphinganine, and was rescued by
      inhibition of ceramide synthase activity. Our findings therefore indicate that
      mitochondrial enrichment of an N-acylated doxSA metabolite may contribute to the
      neurotoxicity seen in diabetic neuropathy and HSAN1. Hence, we provide a
      potential explanation for the characteristic vulnerability of peripheral nerves
      to elevated levels of deoxySLs.

PMID- 27881718
TI  - Variations in vibrissal geometry across the rat mystacial pad: base diameter,
      medulla, and taper.
AB  - Many rodents tactually sense the world through active motions of their vibrissae
      (whiskers), which are regularly arranged in rows and columns (arcs) on the face.
      The present study quantifies several geometric parameters of rat whiskers that
      determine the tactile information acquired. Findings include the following. 1) A
      meta-analysis of seven studies shows that whisker base diameter varies with arc
      length with a surprisingly strong dependence on the whisker's row position within
      the array. 2) The length of the whisker medulla varies linearly with whisker
      length, and the medulla's base diameter varies linearly with whisker base
      diameter. 3) Two parameters are required to characterize whisker "taper": radius
      ratio (base radius divided by tip radius) and radius slope (the difference
      between base and tip radius, divided by arc length). A meta-analysis of five
      studies shows that radius ratio exhibits large variability due to variations in
      tip radius, while radius slope varies systematically across the array. 4) Within
      the resolution of the present study, radius slope does not differ between the
      proximal and distal segments of the whisker, where "proximal" is defined by the
      presence of the medulla. 5) Radius slope of the medulla is offset by a constant
      value from radius slope of the proximal portion of the whisker. We conclude with
      equations for all geometric parameters as functions of row and column
      position.NEW & NOTEWORTHY Rats tactually explore their world by brushing and
      tapping their whiskers against objects. Each whisker's geometry will have a large
      influence on its mechanics and thus on the tactile signals the rat obtains. We
      performed a meta-analysis of seven studies to generate equations that describe
      systematic variations in whisker geometry across the rat's face. We also
      quantified the geometry of the whisker medulla. A database provides access to
      geometric parameters of over 500 rat whiskers.

PMID- 27881720
TI  - Contextual effects of noise on vocalization encoding in primary auditory cortex.
AB  - : Robust auditory perception plays a pivotal function for processing behaviorally
      relevant sounds, particularly with distractions from the environment. The
      neuronal coding enabling this ability, however, is still not well understood. In
      this study, we recorded single-unit activity from the primary auditory cortex
      (A1) of awake marmoset monkeys (Callithrix jacchus) while delivering conspecific
      vocalizations degraded by two different background noises: broadband white noise
      and vocalization babble. Noise effects on neural representation of target
      vocalizations were quantified by measuring the responses' similarity to those
      elicited by natural vocalizations as a function of signal-to-noise ratio. A
      clustering approach was used to describe the range of response profiles by
      reducing the population responses to a summary of four response classes (robust,
      balanced, insensitive, and brittle) under both noise conditions. This clustering
      approach revealed that, on average, approximately two-thirds of the neurons
      change their response class when encountering different noises. Therefore, the
      distortion induced by one particular masking background in single-unit responses
      is not necessarily predictable from that induced by another, suggesting the low
      likelihood of a unique group of noise-invariant neurons across different
      background conditions in A1. Regarding noise influence on neural activities, the
      brittle response group showed addition of spiking activity both within and
      between phrases of vocalizations relative to clean vocalizations, whereas the
      other groups generally showed spiking activity suppression within phrases, and
      the alteration between phrases was noise dependent. Overall, the variable single
      unit responses, yet consistent response types, imply that primate A1 performs
      scene analysis through the collective activity of multiple neurons. NEW &
      NOTEWORTHY: The understanding of where and how auditory scene analysis is
      accomplished is of broad interest to neuroscientists. In this paper, we
      systematically investigated neuronal coding of multiple vocalizations degraded by
      two distinct noises at various signal-to-noise ratios in nonhuman primates. In
      the process, we uncovered heterogeneity of single-unit representations for
      different auditory scenes yet homogeneity of responses across the population.

PMID- 27881719
TI  - Neuronal pattern separation of motion-relevant input in LIP activity.
AB  - In various regions of the brain, neurons discriminate sensory stimuli by
      decreasing the similarity between ambiguous input patterns. Here, we examine
      whether this process of pattern separation may drive the rapid discrimination of
      visual motion stimuli in the lateral intraparietal area (LIP). Starting with a
      simple mean-rate population model that captures neuronal activity in LIP, we show
      that overlapping input patterns can be reformatted dynamically to give rise to
      separated patterns of neuronal activity. The population model predicts that a key
      ingredient of pattern separation is the presence of heterogeneity in the response
      of individual units. Furthermore, the model proposes that pattern separation
      relies on heterogeneity in the temporal dynamics of neural activity and not
      merely in the mean firing rates of individual neurons over time. We confirm these
      predictions in recordings of macaque LIP neurons and show that the accuracy of
      pattern separation is a strong predictor of behavioral performance. Overall,
      results propose that LIP relies on neuronal pattern separation to facilitate
      decision-relevant discrimination of sensory stimuli.NEW & NOTEWORTHY A new
      hypothesis is proposed on the role of the lateral intraparietal (LIP) region of
      cortex during rapid decision making. This hypothesis suggests that LIP alters the
      representation of ambiguous inputs to reduce their overlap, thus improving
      sensory discrimination. A combination of computational modeling, theoretical
      analysis, and electrophysiological data shows that the pattern separation
      hypothesis links neural activity to behavior and offers novel predictions on the
      role of LIP during sensory discrimination.

PMID- 27881721
TI  - Using noise to shape motor learning.
AB  - : Each of our movements is selected from any number of alternative movements.
      Some studies have shown evidence that the central nervous system (CNS) chooses to
      make the specific movements that are least affected by motor noise. Previous
      results showing that the CNS has a natural tendency to minimize the effects of
      noise make the direct prediction that if the relationship between movements and
      noise were to change, the specific movements people learn to make would also
      change in a predictable manner. Indeed, this has been shown for well-practiced
      movements such as reaching. Here, we artificially manipulated the relationship
      between movements and visuomotor noise by adding noise to a motor task in a novel
      redundant geometry such that there arose a single control policy that minimized
      the noise. This allowed us to see whether, for a novel motor task, people could
      learn the specific control policy that minimized noise or would need to employ
      other compensation strategies to overcome the added noise. As predicted, subjects
      were able to learn movements that were biased toward the specific ones that
      minimized the noise, suggesting not only that the CNS can learn to minimize the
      effects of noise in a novel motor task but also that artificial visuomotor noise
      can be a useful tool for teaching people to make specific movements. Using noise
      as a teaching signal promises to be useful for rehabilitative therapies and
      movement training with human-machine interfaces. NEW & NOTEWORTHY: Many theories
      argue that we choose to make the specific movements that minimize motor noise.
      Here, by changing the relationship between movements and noise, we show that
      people actively learn to make movements that minimize noise. This not only
      provides direct evidence for the theories of noise minimization but presents a
      way to use noise to teach specific movements to improve rehabilitative therapies
      and human-machine interface control.

PMID- 27881724
TI  - Spectrum Reconstruction of a Spatially Modulated Fourier Transform Spectrometer
      Based on Stepped Mirrors.
AB  - Based on the basic configuration and interference principle of a static step
      mirror-based Fourier transform spectrometer, an image segmentation method is
      proposed to obtain a one-dimensional interferogram. The direct current component
      of the interferogram is fit using the least squares (LS) method and is
      subsequently removed. An empirical-mode decomposition-method-based high-pass
      filter is constructed to denoise the spectrum and enhance the spectral resolution
      simultaneously. Several experiments were performed and the spectrum is
      reconstructed based on these methods. The spectrum resolution is 81 cm-1 at 2254
      cm-1.

PMID- 27881723
TI  - Intraspinal microstimulation and diaphragm activation after cervical spinal cord
      injury.
AB  - Intraspinal microstimulation (ISMS) using implanted electrodes can evoke
      locomotor movements after spinal cord injury (SCI) but has not been explored in
      the context of respiratory motor output. An advantage over epidural and direct
      muscle stimulation is the potential of ISMS to selectively stimulate components
      of the spinal respiratory network. The present study tested the hypothesis that
      medullary respiratory activity could be used to trigger midcervical ISMS and
      diaphragm motor unit activation in rats with cervical SCI. Studies were conducted
      after acute (hours) and subacute (5-21 days) C2 hemisection (C2Hx) injury in
      adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to
      trigger a 250-ms train stimulus (100 Hz, 100-200 MUA) to the ventral C4 spinal
      cord, targeting the phrenic motor nucleus. After both acute and subacute injury,
      genioglossus EMG activity effectively triggered ISMS and activated diaphragm
      motor units during the inspiratory phase. The ISMS paradigm also evoked short
      term potentiation of spontaneous inspiratory activity in the previously paralyzed
      hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ~70% of
      the C2Hx animals. We conclude that medullary inspiratory output can be used to
      trigger cervical ISMS and diaphragm activity after SCI. Further refinement of
      this method may enable "closed-loop-like" ISMS approaches to sustain ventilation
      after severe SCI.NEW & NOTEWORTHY We examined the feasibility of using
      intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke
      diaphragm activity ipsilateral to acute and subacute hemisection of the upper
      cervical spinal cord of the rat. This proof-of-concept study demonstrated the
      efficacy of diaphragm activation, using an upper airway respiratory EMG signal to
      trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and
      advanced postinjury intervals.

PMID- 27881725
TI  - TATA Box Insertion Provides a Selection Mechanism Underpinning Adaptations to Fe
      Deficiency.
AB  - Intraspecific genetic variation is essential for the responses and adaption of
      plants to evolutionary challenges, such as changing environmental conditions. The
      development of the Earth's aerobic atmosphere has increased the demand for iron
      (Fe) in organisms, and Fe deficiency has become a limiting environmental factor
      for plant growth. Here, we demonstrate that genus Malus adapt to Fe deficiency
      through modification of the Iron-Regulated Transporter1 (IRT1) promoter.
      Specifically, an IRT1 mutant allele with a TATA-box insertion in the promoter
      region upstream of the coding region exhibited increased IRT1 expression. The
      altered IRT1 promoter is responsible for enhancing Fe uptake. Increasing the
      number of synthetic repeat TATA-boxes correlates with increased promoter
      activity. Furthermore, we demonstrate that the insertion of the TATA-box
      correlates with an increase in transcriptional activation via specific binding of
      the transcription factor IID (MDP0000939369). Taken together, these results
      indicate that an allelic insertion of a TATA-box in a gene promoter has allowed
      apple to adapt to the selective pressure posed by Fe deficiency. More broadly,
      this study reveals a new mechanism for enhancing gene expression to help plants
      adapt to different environments, providing new insights into molecular genetic
      divergence in plants.

PMID- 27881722
TI  - Maintenance of neuronal size gradient in MNTB requires sound-evoked activity.
AB  - The medial nucleus of the trapezoid body (MNTB) is an important source of
      inhibition during the computation of sound location. It transmits fast and
      precisely timed action potentials at high frequencies; this requires an efficient
      calcium clearance mechanism, in which plasma membrane calcium ATPase 2 (PMCA2) is
      a key component. Deafwaddler (dfw2J ) mutant mice have a null mutation in PMCA2
      causing deafness in homozygotes (dfw2J /dfw2J ) and high-frequency hearing loss
      in heterozygotes (+/dfw2J ). Despite the deafness phenotype, no significant
      differences in MNTB volume or cell number were observed in dfw2J homozygous
      mutants, suggesting that PMCA2 is not required for MNTB neuron survival. The MNTB
      tonotopic axis encodes high to low sound frequencies across the medial to lateral
      dimension. We discovered a cell size gradient along this axis: lateral neuronal
      somata are significantly larger than medially located somata. This size gradient
      is decreased in +/dfw2J and absent in dfw2J /dfw2J The lack of acoustically
      driven input suggests that sound-evoked activity is required for maintenance of
      the cell size gradient. This hypothesis was corroborated by selective elimination
      of auditory hair cell activity with either hair cell elimination in Pou4f3 DTR
      mice or inner ear tetrodotoxin (TTX) treatment. The change in soma size was
      reversible and recovered within 7 days of TTX treatment, suggesting that
      regulation of the gradient is dependent on synaptic activity and that these
      changes are plastic rather than permanent.NEW & NOTEWORTHY Neurons of the medial
      nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons
      within the auditory brain stem. The MNTB is topographically organized, with low
      sound frequencies encoded laterally and high frequencies medially. We discovered
      a cell size gradient along this axis: lateral neurons are larger than medial
      neurons. The absence of this gradient in deaf mice lacking plasma membrane
      calcium ATPase 2 suggests an activity-dependent, calcium-mediated mechanism that
      controls neuronal soma size.

PMID- 27881726
TI  - Systems Genetics Identifies a Novel Regulatory Domain of Amylose Synthesis.
AB  - A deeper understanding of the regulation of starch biosynthesis in rice (Oryza
      sativa) endosperm is crucial in tailoring digestibility without sacrificing grain
      quality. In this study, significant association peaks on chromosomes 6 and 7 were
      identified through a genomewide association study (GWAS) of debranched starch
      structure from grains of a 320 indica rice diversity panel using genotyping data
      from the high-density rice array. A systems genetics approach that interrelates
      starch structure data from GWAS to functional pathways from a gene regulatory
      network identified known genes with high correlation to the proportion of amylose
      and amylopectin. An SNP in the promoter region of Granule Bound Starch Synthase I
      was identified along with seven other SNPs to form haplotypes that discriminate
      samples into different phenotypic ranges of amylose. A GWAS peak on chromosome 7
      between LOC_Os07g11020 and LOC_Os07g11520 indexed by a nonsynonymous SNP mutation
      on exon 5 of a bHLH transcription factor was found to elevate the proportion of
      amylose at the expense of reduced short-chain amylopectin. Linking starch
      structure with starch digestibility by determining the kinetics of cooked grain
      amylolysis of selected haplotypes revealed strong association of starch structure
      with estimated digestibility kinetics. Combining all results from grain quality
      genomics, systems genetics, and digestibility phenotyping, we propose target
      haplotypes for fine-tuning starch structure in rice through marker-assisted
      breeding that can be used to alter the digestibility of rice grain, thus offering
      rice consumers a new diet-based intervention to mitigate the impact of nutrition
      related noncommunicable diseases.

PMID- 27881727
TI  - A Tightly Regulated Genetic Selection System with Signaling-Active Alleles of
      Phytochrome B.
AB  - Selectable markers derived from plant genes circumvent the potential risk of
      antibiotic/herbicide-resistance gene transfer into neighboring plant species,
      endophytic bacteria, and mycorrhizal fungi. Toward this goal, we have engineered
      and validated signaling-active alleles of phytochrome B (eYHB) as plant-derived
      selection marker genes in the model plant Arabidopsis (Arabidopsis thaliana). By
      probing the relationship of construct size and induction conditions to optimal
      phenotypic selection, we show that eYHB-based alleles are robust substitutes for
      antibiotic/herbicide-dependent marker genes as well as surprisingly sensitive
      reporters of off-target transgene expression.

PMID- 27881730
TI  - Breast Cancer, Breastfeeding, and Mastectomy: A Call for More Research.

PMID- 27881729
TI  - Brazilian Immigrant Mothers' Beliefs and Practices Related to Infant Feeding: A
      Qualitative Study.
AB  - BACKGROUND: Exclusive breastfeeding for the first 6 months of life and timely
      introduction of appropriate solid foods are important determinants of weight
      status in infancy and later life stages. Disparities in obesity rates among young
      children suggest that maternal feeding practices during the first 2 years of life
      may contribute to these disparities. Brazilians are a growing immigrant group in
      the United States, yet little research has focused on parental beliefs and
      behaviors affecting the health of Brazilian immigrant children in the United
      States. Research aim: This study aimed to explore beliefs and infant-feeding
      practices of Brazilian immigrant mothers in the United States. METHODS: Focus
      group discussions were conducted with Brazilian immigrant mothers. Transcripts
      were analyzed using thematic analysis and themes categorized using the
      socioecological model. RESULTS: Twenty-nine immigrant Brazilian mothers
      participated in the study. Analyses revealed that all participants breastfed
      their infants. The majority initiated breastfeeding soon after childbirth.
      However, most mothers did not exclusively breastfeed. They used formula and human
      milk concomitantly. Family and culture influenced mothers' infant-feeding beliefs
      and practices in early introduction of solid foods. CONCLUSION: As the number of
      children in the United States growing up in families of immigrant parents
      increases, understanding influences on Brazilian immigrant mothers' infant
      feeding practices will be important to the development of effective interventions
      to promote healthy infant feeding and weight status among Brazilian children.
      Interventions designed for Brazilian immigrant families should incorporate an
      understanding of social context, family, and cultural factors to develop health
      promotion messages tailored to the needs of this ethnic group.

PMID- 27881728
TI  - A DII Domain-Based Auxin Reporter Uncovers Low Auxin Signaling during Telophase
      and Early G1.
AB  - A sensitive and dynamically responsive auxin signaling reporter based on the DII
      domain of the INDOLE-3-ACETIC ACID28 (IAA28, DII) protein from Arabidopsis
      (Arabidopsis thaliana) was modified for use in maize (Zea mays). The DII domain
      was fused to a yellow fluorescent protein and a nuclear localization sequence to
      simplify quantitative nuclear fluorescence signal. DII degradation dynamics
      provide an estimate of input signal into the auxin signaling pathway that is
      influenced by both auxin accumulation and F-box coreceptor concentration. In
      maize, the DII-based marker responded rapidly and in a dose-dependent manner to
      exogenous auxin via proteasome-mediated degradation. Low levels of DII-specific
      fluorescence corresponding to high endogenous auxin signaling occurred near
      vasculature tissue and the outer layer and glume primordia of spikelet pair
      meristems and floral meristems, respectively. In addition, high DII levels were
      observed in cells during telophase and early G1, suggesting that low auxin
      signaling at these stages may be important for cell cycle progression.

PMID- 27881731
TI  - Factors Distinguishing Positive Deviance Among Low-Income African American Women:
      A Qualitative Study on Infant Feeding.
AB  - BACKGROUND: Positive deviant individuals practice beneficial behaviors in spite
      of having qualities characterizing them as high risk for unhealthy behaviors.
      OBJECTIVE: This study aimed to identify and understand factors distinguishing low
      income African American women who breastfeed the longest (positive deviants) from
      those who breastfeed for a shorter duration or do not breastfeed. METHODS: Seven
      mini-focus groups on infant-feeding attitudes and experiences were conducted with
      25 low-income African American women, grouped by infant-feeding practice.
      Positive deviants, who had breastfed for 4 months or more, were compared with
      formula-feeding participants who had only formula fed their babies and short-term
      breastfeeding participants who had breastfed for 3 months or less. RESULTS:
      Positive deviant women had more schooling, higher income, breastfeeding
      intention, positive breastfeeding and unfavorable formula-feeding attitudes,
      higher self-efficacy, positive hospital and Special Supplemental Nutrition
      Program for Women, Infants, and Children experiences, more exclusive
      breastfeeding, and greater comfort breastfeeding in public. Short-term
      breastfeeding women varied in breastfeeding intention and self-efficacy, seemed
      to receive insufficient professional breastfeeding support, and supplemented
      breastfeeding with formula. Some showed ambivalence, concern with unhealthy
      behaviors, and discomfort with breastfeeding in public. Formula-feeding women
      intended to formula feed, feared breastfeeding, thought their behaviors were
      incompatible with breastfeeding, were comfortable with and found formula
      convenient, and received strong support to formula feed. CONCLUSION: Tapping into
      the strengths of positive deviants; tailoring interventions to levels of general
      and breastfeeding self-efficacy; increasing social, institutional, and community
      supports; and removing inappropriate formula promotion may offer promising
      strategies to increase breastfeeding among low-income African American women.

PMID- 27881732
TI  - Metronomic chemotherapy prevents therapy-induced stromal activation and induction
      of tumor-initiating cells.
AB  - Although traditional chemotherapy kills a fraction of tumor cells, it also
      activates the stroma and can promote the growth and survival of residual cancer
      cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host
      response induced by chemotherapy could substantially improve therapeutic outcome
      and patient survival. In this study, resistance to treatment and metastasis has
      been attributed to expansion of stem-like tumor-initiating cells (TICs).
      Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human
      desmoplastic cancers and orthotopic tumor xenografts revealed that traditional
      maximum-tolerated dose chemotherapy, regardless of the agents used, induces
      persistent STAT-1 and NF-kappaB activity in carcinoma-associated fibroblasts.
      This induction results in the expression and secretion of ELR motif-positive
      (ELR+) chemokines, which signal through CXCR-2 on carcinoma cells to trigger
      their phenotypic conversion into TICs and promote their invasive behaviors,
      leading to paradoxical tumor aggression after therapy. In contrast, the same
      overall dose administered as a low-dose metronomic chemotherapy regimen largely
      prevented therapy-induced stromal ELR+ chemokine paracrine signaling, thus
      enhancing treatment response and extending survival of mice carrying desmoplastic
      cancers. These experiments illustrate the importance of stroma in cancer therapy
      and how its impact on treatment resistance could be tempered by altering the
      dosing schedule of systemic chemotherapy.

PMID- 27881733
TI  - Lysosomal trafficking regulator Lyst links membrane trafficking to toll-like
      receptor-mediated inflammatory responses.
AB  - Subcellular compartmentalization of receptor signaling is an emerging principle
      in innate immunity. However, the functional integration of receptor signaling
      pathways into membrane trafficking routes and its physiological relevance for
      immune responses is still largely unclear. In this study, using Lyst-mutant beige
      mice, we show that lysosomal trafficking regulator Lyst links endolysosomal
      organization to the selective control of toll-like receptor 3 (TLR3)- and TLR4
      mediated proinflammatory responses. Consequently, Lyst-mutant mice showed
      increased susceptibility to bacterial infection and were largely resistant to
      endotoxin-induced septic shock. Mechanistic analysis revealed that Lyst
      specifically controls TLR3- and TLR4-induced endosomal TRIF (TIR domain
      containing adapter-inducing interferon beta) signaling pathways. Loss of
      functional Lyst leads to dysregulated phagosomal maturation, resulting in a
      failure to form an activation-induced Rab7+ endosomal/phagosomal compartment.
      This specific Rab7+ compartment was further demonstrated to serve as a major site
      for active TRIF signaling events, thus linking phagosomal maturation to specific
      TLR signaling pathways. The immunoregulatory role of Lyst on TLR signaling
      pathways was confirmed in human cells by CRISPR/Cas9-mediated gene inactivation.
      As mutations in LYST cause human Chediak-Higashi syndrome, a severe
      immunodeficiency, our findings also contribute to a better understanding of human
      disease mechanisms.

PMID- 27881735
TI  - Therapy-activated stromal cells can dictate tumor fate.
AB  - In this issue of JEM, Chan et al. describe a novel way by which an
      investigational form of chemotherapy known as low-dose metronomic chemotherapy
      can inhibit tumor growth, which also has therapeutic implications for targeting
      tumor-initiating cells (TICs), the tumor stroma, and chemokine receptors, as well
      as invasion and metastasis.

PMID- 27881734
TI  - NLRP2 controls age-associated maternal fertility.
AB  - Nucleotide-binding domain and leucine-rich repeat (NLR) proteins are well-known
      for their key roles in the immune system. Ectopically expressed NLRP2 in
      immortalized cell lines assembles an inflammasome and inhibits activation of the
      proinflammatory transcription factor NF-kappaB, but the physiological roles of
      NLRP2 are unknown. Here, we show that Nlrp2-deficient mice were born with
      expected Mendelian ratios and that Nlrp2 was dispensable for innate and adaptive
      immunity. The observation that Nlrp2 was exclusively expressed in oocytes led us
      to explore the role of Nlrp2 in parthenogenetic activation of oocytes.
      Remarkably, unlike oocytes of young adult Nlrp2-deficient mice, activated oocytes
      of mature adult mice developed slower and largely failed to reach the blastocyst
      stage. In agreement, we noted strikingly declining reproductive rates in vivo
      with progressing age of female Nlrp2-deficient mice. This work identifies Nlrp2
      as a critical regulator of oocyte quality and suggests that NLRP2 variants with
      reduced activity may contribute to maternal age-associated fertility loss in
      humans.

PMID- 27881736
TI  - Reactive oxygen species drive evolution of pro-biofilm variants in pathogens by
      modulating cyclic-di-GMP levels.
AB  - The host immune system offers a hostile environment with antimicrobials and
      reactive oxygen species (ROS) that are detrimental to bacterial pathogens,
      forcing them to adapt and evolve for survival. However, the contribution of
      oxidative stress to pathogen evolution remains elusive. Using an experimental
      evolution strategy, we show that exposure of the opportunistic pathogen
      Pseudomonas aeruginosa to sub-lethal hydrogen peroxide (H2O2) levels over 120
      generations led to the emergence of pro-biofilm rough small colony variants
      (RSCVs), which could be abrogated by l-glutathione antioxidants. Comparative
      genomic analysis of the RSCVs revealed that mutations in the wspF gene, which
      encodes for a repressor of WspR diguanylate cyclase (DGC), were responsible for
      increased intracellular cyclic-di-GMP content and production of Psl
      exopolysaccharide. Psl provides the first line of defence against ROS and
      macrophages, ensuring the survival fitness of RSCVs over wild-type P. aeruginosa
      Our study demonstrated that ROS is an essential driving force for the selection
      of pro-biofilm forming pathogenic variants. Understanding the fundamental
      mechanism of these genotypic and phenotypic adaptations will improve treatment
      strategies for combating chronic infections.

PMID- 27881737
TI  - RANKL/RANK: from bone loss to the prevention of breast cancer.
AB  - RANK and RANKL, a receptor ligand pair belonging to the tumour necrosis factor
      family, are the critical regulators of osteoclast development and bone
      metabolism. Besides their essential function in bone, RANK and RANKL have also
      been identified as the key factors for the formation of a lactating mammary gland
      in pregnancy. Mechanistically, RANK and RANKL link the sex hormone progesterone
      with stem cell expansion and proliferation of mammary epithelial cells. Based on
      their normal physiology, RANKL/RANK control the onset of hormone-induced breast
      cancer through the expansion of mammary progenitor cells. Recently, we and others
      were able to show that RANK and RANKL are also critical regulators of BRCA1
      mutation-driven breast cancer. Currently, the preventive strategy for BRCA1
      mutation carriers includes preventive mastectomy, associated with wide-ranging
      risks and psychosocial effects. The search for an alternative non-invasive
      prevention strategy is therefore of paramount importance. As our work strongly
      implicates RANK and RANKL as key molecules involved in the initiation of BRCA1
      associated breast cancer, we propose that anti-RANKL therapy could be a feasible
      preventive strategy for women carrying BRCA1 mutations, and by extension to other
      women with high risk of breast cancer.

PMID- 27881738
TI  - Human selenoprotein P and S variant mRNAs with different numbers of SECIS
      elements and inferences from mutant mice of the roles of multiple SECIS elements.
AB  - Dynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1)
      mRNAs to specify selenocysteine instead of termination involves two 3' UTR
      structural elements (SECIS) and is regulated by selenium availability. In
      addition to the previously known human Sepp1 mRNA poly(A) addition site just 3'
      of SECIS 2, two further sites were identified with one resulting in 10-25% of the
      mRNA lacking SECIS 2. To address function, mutant mice were generated with either
      SECIS 1 or SECIS 2 deleted or with the first UGA substituted with a serine codon.
      They were fed on either high or selenium-deficient diets. The mutants had very
      different effects on the proportions of shorter and longer product Sepp1 protein
      isoforms isolated from plasma, and on viability. Spatially and functionally
      distinctive effects of the two SECIS elements on UGA decoding were inferred. We
      also bioinformatically identify two selenoprotein S mRNAs with different 5'
      sequences predicted to yield products with different N-termini. These results
      provide insights into SECIS function and mRNA processing in selenoprotein isoform
      diversity.

PMID- 27881741
TI  - Correction to 'Identification of the critical residues responsible for
      differential reactivation of the triosephosphate isomerases of two trypanosomes'.

PMID- 27881739
TI  - The functional readthrough extension of malate dehydrogenase reveals a
      modification of the genetic code.
AB  - Translational readthrough gives rise to C-terminally extended proteins, thereby
      providing the cell with new protein isoforms. These may have different properties
      from the parental proteins if the extensions contain functional domains. While
      for most genes amino acid incorporation at the stop codon is far lower than 0.1%,
      about 4% of malate dehydrogenase (MDH1) is physiologically extended by
      translational readthrough and the actual ratio of MDH1x (extended protein) to
      'normal' MDH1 is dependent on the cell type. In human cells, arginine and
      tryptophan are co-encoded by the MDH1x UGA stop codon. Readthrough is controlled
      by the 7-nucleotide high-readthrough stop codon context without contribution of
      the subsequent 50 nucleotides encoding the extension. All vertebrate MDH1x is
      directed to peroxisomes via a hidden peroxisomal targeting signal (PTS) in the
      readthrough extension, which is more highly conserved than the extension of
      lactate dehydrogenase B. The hidden PTS of non-mammalian MDH1x evolved to be more
      efficient than the PTS of mammalian MDH1x. These results provide insight into the
      genetic and functional co-evolution of these dually localized dehydrogenases.

PMID- 27881742
TI  - Association of Abnormal Metatarsal Parabola With Second Metatarsophalangeal Joint
      Plantar Plate Pathology.
AB  - BACKGROUND: Plantar plate pathology is common, yet it is unclear whether, and to
      what extent, the length of the second metatarsal contributes to this problem.
      METHODS: We conducted a retrospective case-control (1:2) study to examine
      radiographic risk factors for plantar plate tears. One hundred patients (age 55.7
      +/- 12.3 years) with plantar plate injuries and 200 healthy controls (age 56.3 +/
      11.3 years) were included. Cases were defined as patients with nonacute,
      isolated, plantar plate pathology of the second metatarsophalangeal joint
      confirmed by intraoperative inspection at a single foot and ankle specialty
      practice from June 1, 2007, to January 31, 2014. Patients presenting for pain
      outside of the forefoot served as the control group. Controls were matched on age
      (+/-2 years), gender, and year of presentation. Weight-bearing foot x-rays were
      assessed for several predetermined angular relationships by a single rater.
      Conditional logistic regression was used to identify risk factors for plantar
      plate injury. RESULTS: A long second metatarsal, defined as a metatarsal
      protrusion index less than -4 mm, was the only significant risk factor for
      plantar plate pathology in both the univariate and multivariable analyses
      (multivariate odds ratio 2.5 [95% confidence interval 1.8 to 3.3], P = .002).
      CONCLUSION: We found that a long second metatarsal was a risk factor for
      developing second metatarsophalangeal joint plantar plate tears. This knowledge
      may aid foot and ankle surgeons when contemplating the need for second metatarsal
      shortening osteotomies (eg, Weil osteotomy) during plantar plate surgery and when
      deciding on the amount of shortening for second metatarsal osteotomies. LEVEL OF
      EVIDENCE: Level III, retrospective comparative study.

PMID- 27881740
TI  - Peripheral self-reactivity regulates antigen-specific CD8 T-cell responses and
      cell division under physiological conditions.
AB  - T-cell identity is established by the expression of a clonotypic T-cell receptor
      (TCR), generated by somatic rearrangement of TCRalpha and beta genes. The
      properties of the TCR determine both the degree of self-reactivity and the
      repertoire of antigens that can be recognized. For CD8 T cells, the relationship
      between TCR identity-hence reactivity to self-and effector function(s) remains to
      be fully understood and has rarely been explored outside of the H-2b haplotype.
      We measured the affinity of three structurally distinct CD8 T-cell-derived TCRs
      that recognize the identical H-2 Ld-restricted epitope, derived from the Rop7
      protein of Toxoplasma gondii We used CD8 T cells obtained from mice generated by
      somatic cell nuclear transfer as the closest approximation of primary T cells
      with physiological TCR rearrangements and TCR expression levels. First, we
      demonstrate the common occurrence of secondary rearrangements in endogenously
      rearranged loci. Furthermore, we characterized and compared the response of Rop7
      specific CD8 T-cell clones upon Toxoplasma gondii infection as well as effector
      function and TCR signalling upon antigenic stimulation in vitro Antigen
      independent TCR cross-linking in vitro uncovered profound intrinsic differences
      in the effector functions between T-cell clones. Finally, by assessing the degree
      of self-reactivity and comparing the transcriptomes of naive Rop7 CD8 T cells, we
      show that lower self-reactivity correlates with lower effector capacity, whereas
      higher self-reactivity is associated with enhanced effector function as well as
      cell cycle entry under physiological conditions. Altogether, our data show that
      potential effector functions and basal proliferation of CD8 T cells are set by
      self-reactivity thresholds.

PMID- 27881743
TI  - Intralocus sexual conflict and insecticide resistance.
AB  - The BA allele of the Drosophila cytochrome P450 gene Cyp6g1 confers resistance to
      a range of insecticides. It is also subject to intralocus sexual conflict when
      introgressed into the Canton-S background, whose collection predates the
      widespread use of insecticides. In this genetic background, the allele confers a
      pleiotropic fitness benefit to females but a cost to males, and exhibits little
      sexual dimorphism in conferred insecticide resistance. It is unclear whether
      these sexually antagonistic effects also exist in current populations that have
      naturally evolved with insecticides, where genetic modifiers that offset male
      costs might be expected to evolve. Here, we explore these issues using Drosophila
      melanogaster caught recently from an Australian population in which the BA allele
      naturally segregates. While we find increased fecundity in insecticide-resistant
      BA females and no consistent evidence of fitness costs in males, experimental
      evolution indicates balancing selection at the locus. We suggest that this
      apparent discrepancy may be due to reduced investment in reproduction in
      resistant males. Our results at the population level are consistent with previous
      work, and suggest that individual-level fitness assays do not always capture
      sexually antagonistic fitness effects that emerge in a population context.

PMID- 27881744
TI  - Directional selection effects on patterns of phenotypic (co)variation in wild
      populations.
AB  - Phenotypic (co)variation is a prerequisite for evolutionary change, and
      understanding how (co)variation evolves is of crucial importance to the
      biological sciences. Theoretical models predict that under directional selection,
      phenotypic (co)variation should evolve in step with the underlying adaptive
      landscape, increasing the degree of correlation among co-selected traits as well
      as the amount of genetic variance in the direction of selection. Whether either
      of these outcomes occurs in natural populations is an open question and thus an
      important gap in evolutionary theory. Here, we documented changes in the
      phenotypic (co)variation structure in two separate natural populations in each of
      two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional
      selection. In populations where selection was strongest (those of T. alpinus), we
      observed changes, at least for one population, in phenotypic (co)variation that
      matched theoretical expectations, namely an increase of both phenotypic
      integration and (co)variance in the direction of selection and a re-alignment of
      the major axis of variation with the selection gradient.

PMID- 27881745
TI  - Natural bounds on herbivorous coral reef fishes.
AB  - Humans are an increasingly dominant driver of Earth's biological communities, but
      differentiating human impacts from natural drivers of ecosystem state is crucial.
      Herbivorous fish play a key role in maintaining coral dominance on coral reefs,
      and are widely affected by human activities, principally fishing. We assess the
      relative importance of human and biophysical (habitat and oceanographic) drivers
      on the biomass of five herbivorous functional groups among 33 islands in the
      central and western Pacific Ocean. Human impacts were clear for some, but not
      all, herbivore groups. Biomass of browsers, large excavators, and of all
      herbivores combined declined rapidly with increasing human population density,
      whereas grazers, scrapers, and detritivores displayed no relationship. Sea
      surface temperature had significant but opposing effects on the biomass of
      detritivores (positive) and browsers (negative). Similarly, the biomass of
      scrapers, grazers, and detritivores correlated with habitat structural
      complexity; however, relationships were group specific. Finally, the biomass of
      browsers and large excavators was related to island geomorphology, both peaking
      on low-lying islands and atolls. The substantial variability in herbivore
      populations explained by natural biophysical drivers highlights the need for
      locally appropriate management targets on coral reefs.

PMID- 27881746
TI  - Neotropical wrens learn new duet rules as adults.
AB  - Although song development in songbirds has been much studied as an analogue of
      language development in humans, the development of vocal interaction rules has
      been relatively neglected in both groups. Duetting avian species provide an ideal
      model to address the acquisition of interaction rules as duet structure involves
      time and pattern-specific relationships among the vocalizations from different
      individuals. In this study, we address the development of the most striking
      properties of duets: the specific answering rules that individuals use to link
      their own phrase types to those of their partners (duet codes) and precise
      temporal coordination. By performing two removal experiments in canebrake wrens
      (Cantorchilus zeledoni), we show that individuals use a fixed phrase repertoire
      to create new phrase pairings when they acquire a new partner. Furthermore,
      immediately after pairing, individuals perform duets with poor coordination and
      poor duet code adherence, but both aspects improve with time. These results
      indicate that individuals need a learning period to be able to perform well
      coordinated duets that follow a consistent duet code. We conclude that both duet
      coordination and duet code adherence are honest indicators of pair-bond duration.

PMID- 27881748
TI  - Rates of change in climatic niches in plant and animal populations are much
      slower than projected climate change.
AB  - Climate change may soon threaten much of global biodiversity. A critical question
      is: can species undergo niche shifts of sufficient speed and magnitude to persist
      within their current geographic ranges? Here, we analyse niche shifts among
      populations within 56 plant and animal species using time-calibrated trees from
      phylogeographic studies. Across 266 phylogeographic groups analysed, rates of
      niche change were much slower than rates of projected climate change (mean
      difference > 200 000-fold for temperature variables). Furthermore, the absolute
      niche divergence among populations was typically lower than the magnitude of
      projected climate change over the next approximately 55 years for relevant
      variables, suggesting the amount of change needed to persist may often be too
      great, even if these niche shifts were instantaneous. Rates were broadly similar
      between plants and animals, but especially rapid in some arthropods, birds and
      mammals. Rates for temperature variables were lower at lower latitudes, further
      suggesting that tropical species may be especially vulnerable to climate change.

PMID- 27881747
TI  - Inbreeding parents should invest more resources in fewer offspring.
AB  - Inbreeding increases parent-offspring relatedness and commonly reduces offspring
      viability, shaping selection on reproductive interactions involving relatives and
      associated parental investment (PI). Nevertheless, theories predicting selection
      for inbreeding versus inbreeding avoidance and selection for optimal PI have only
      been considered separately, precluding prediction of optimal PI and associated
      reproductive strategy given inbreeding. We unify inbreeding and PI theory,
      demonstrating that optimal PI increases when a female's inbreeding decreases the
      viability of her offspring. Inbreeding females should therefore produce fewer
      offspring due to the fundamental trade-off between offspring number and PI.
      Accordingly, selection for inbreeding versus inbreeding avoidance changes when
      females can adjust PI with the degree that they inbreed. By contrast, optimal PI
      does not depend on whether a focal female is herself inbred. However, inbreeding
      causes optimal PI to increase given strict monogamy and associated biparental
      investment compared with female-only investment. Our model implies that
      understanding evolutionary dynamics of inbreeding strategy, inbreeding
      depression, and PI requires joint consideration of the expression of each in
      relation to the other. Overall, we demonstrate that existing PI and inbreeding
      theories represent special cases of a more general theory, implying that
      intrinsic links between inbreeding and PI affect evolution of behaviour and
      intrafamilial conflict.

PMID- 27881749
TI  - Vive la resistance: genome-wide selection against introduced alleles in invasive
      hybrid zones.
AB  - Evolutionary and ecological consequences of hybridization between native and
      invasive species are notoriously complicated because patterns of selection acting
      on non-native alleles can vary throughout the genome and across environments.
      Rapid advances in genomics now make it feasible to assess locus-specific and
      genome-wide patterns of natural selection acting on invasive introgression within
      and among natural populations occupying diverse environments. We quantified
      genome-wide patterns of admixture across multiple independent hybrid zones of
      native westslope cutthroat trout and invasive rainbow trout, the world's most
      widely introduced fish, by genotyping 339 individuals from 21 populations using
      9380 species-diagnostic loci. A significantly greater proportion of the genome
      appeared to be under selection favouring native cutthroat trout (rather than
      rainbow trout), and this pattern was pervasive across the genome (detected on
      most chromosomes). Furthermore, selection against invasive alleles was consistent
      across populations and environments, even in those where rainbow trout were
      predicted to have a selective advantage (warm environments). These data
      corroborate field studies showing that hybrids between these species have lower
      fitness than the native taxa, and show that these fitness differences are due to
      selection favouring many native genes distributed widely throughout the genome.

PMID- 27881750
TI  - Experimental evidence that honeybees depress wild insect densities in a flowering
      crop.
AB  - While addition of managed honeybees (Apis mellifera) improves pollination of many
      entomophilous crops, it is unknown if it simultaneously suppresses the densities
      of wild insects through competition. To investigate this, we added 624 honeybee
      hives to 23 fields of oilseed rape (Brassica napus L.) over 2 years and made sure
      that the areas around 21 other fields were free from honeybee hives. We
      demonstrate that honeybee addition depresses the densities of wild insects
      (bumblebees, solitary bees, hoverflies, marchflies, other flies, and other flying
      and flower-visiting insects) even in a massive flower resource such as oilseed
      rape. The effect was independent of the complexity of the surrounding landscape,
      but increased with the size of the crop field, which suggests that the effect was
      caused by spatial displacement of wild insects. Our results have potential
      implications both for the pollination of crops (if displacement of wild
      pollinators offsets benefits achieved by adding honeybees) and for conservation
      of wild insects (if displacement results in negative fitness consequences).

PMID- 27881751
TI  - Artificial selection on male genitalia length alters female brain size.
AB  - Male harassment is a classic example of how sexual conflict over mating leads to
      sex-specific behavioural adaptations. Females often suffer significant costs from
      males attempting forced copulations, and the sexes can be in an arms race over
      male coercion. Yet, despite recent recognition that divergent sex-specific
      interests in reproduction can affect brain evolution, sexual conflict has not
      been addressed in this context. Here, we investigate whether artificial selection
      on a correlate of male success at coercion, genital length, affects brain anatomy
      in males and females. We analysed the brains of eastern mosquitofish (Gambusia
      holbrooki), which had been artificially selected for long or short gonopodium,
      thereby mimicking selection arising from differing levels of male harassment. By
      analogy to how prey species often have relatively larger brains than their
      predators, we found that female, but not male, brain size was greater following
      selection for a longer gonopodium. Brain subregion volumes remained unchanged.
      These results suggest that there is a positive genetic correlation between male
      gonopodium length and female brain size, which is possibly linked to increased
      female cognitive ability to avoid male coercion. We propose that sexual conflict
      is an important factor in the evolution of brain anatomy and cognitive ability.

PMID- 27881752
TI  - Female monkeys use both the carrot and the stick to promote male participation in
      intergroup fights.
AB  - Group-level cooperation often poses a social dilemma in which joint action may be
      difficult to achieve. Theoretical models and experimental work on humans show
      that social incentives, such as punishment of defectors and rewarding of
      cooperators, can promote cooperation in groups of unrelated individuals. Here, we
      demonstrate that these processes can operate in a non-human animal species, and
      be used to effectively promote the production of a public good. We took advantage
      of the fact that intergroup fights in vervet monkeys (Chlorocebus aethiops
      pygerythrus) are characterized by episodes of intergroup aggression with pauses
      in-between. During pauses, females selectively groomed males that had
      participated in the previous aggressive episode, but aggressed male group members
      that had not. In subsequent (i.e. future) episodes, males who had received either
      aggression or grooming participated above their personal base-line level.
      Therefore, female-male aggression and grooming both appear to function as social
      incentives that effectively promote male participation in intergroup fights.
      Importantly, females stood to gain much from recruiting males as the probability
      of winning intergroup fights was dependent on the number of active participants,
      relative to the number of fighters in the opposing group. Furthermore, females
      appear to maximize the benefits gained from recruiting males as they primarily
      used social incentives where and when high-quality food resources, which are the
      resources primarily limiting to female fitness, were at stake.

PMID- 27881753
TI  - How can we estimate natural selection on endocrine traits? Lessons from
      evolutionary biology.
AB  - An evolutionary perspective can enrich almost any endeavour in biology, providing
      a deeper understanding of the variation we see in nature. To this end,
      evolutionary endocrinologists seek to describe the fitness consequences of
      variation in endocrine traits. Much of the recent work in our field, however,
      follows a flawed approach to the study of how selection shapes endocrine traits.
      Briefly, this approach relies on among-individual correlations between endocrine
      phenotypes (often circulating hormone levels) and fitness metrics to estimate
      selection on those endocrine traits. Adaptive plasticity in both endocrine and
      fitness-related traits can drive these correlations, generating patterns that do
      not accurately reflect natural selection. We illustrate why this approach to
      studying selection on endocrine traits is problematic, referring to work from
      evolutionary biologists who, decades ago, described this problem as it relates to
      a variety of other plastic traits. We extend these arguments to evolutionary
      endocrinology, where the likelihood that this flaw generates bias in estimates of
      selection is unusually high due to the exceptional responsiveness of hormones to
      environmental conditions, and their function to induce adaptive life-history
      responses to environmental variation. We end with a review of productive
      approaches for investigating the fitness consequences of variation in endocrine
      traits that we expect will generate exciting advances in our understanding of
      endocrine system evolution.

PMID- 27881754
TI  - Neuroendocrine correlates of sex-role reversal in barred buttonquails.
AB  - Sex differences in brain structure and behaviour are well documented among
      vertebrates. An excellent model exploring the neural mechanisms of sex
      differences in behaviour is represented by sex-role-reversed species. In the
      majority of bird species, males compete over access to mates and resources more
      strongly than do females. It is thought that the responsible brain regions are
      therefore more developed in males than in females. Because these behaviours and
      brain regions are activated by androgens, males usually have increased
      testosterone levels during breeding. Therefore, in species with sex-role
      reversal, certain areas of the female brain should be more developed or steroid
      hormone profiles should be sexually reversed. Here, I studied circulating hormone
      levels and gene expression of steroid hormone receptors and aromatase in a
      captive population of barred buttonquails (Turnix suscitator). While females
      performed courtship and agonistic behaviours, there was no evidence for sexually
      reversed hormone profiles. However, I found female-biased sex differences in gene
      expression of androgen receptors in several hypothalamic and limbic brain regions
      that were already in place at hatching. Such sex differences are not known from
      non-sex-role-reversed species. These data suggest that increased neural
      sensitivity to androgens could be involved in the mechanisms mediating sex-role
      reversed behaviours.

PMID- 27881756
TI  - A combinatorial approach to angiosperm pollen morphology.
AB  - Angiosperms (flowering plants) are strikingly diverse. This is clearly expressed
      in the morphology of their pollen grains, which are characterized by enormous
      variety in their shape and patterning. In this paper, I approach angiosperm
      pollen morphology from the perspective of enumerative combinatorics. This
      involves generating angiosperm pollen morphotypes by algorithmically combining
      character states and enumerating the results of these combinations. I use this
      approach to generate 3 643 200 pollen morphotypes, which I visualize using a
      parallel-coordinates plot. This represents a raw morphospace. To compare real
      world and theoretical morphologies, I map the pollen of 1008 species of
      Neotropical angiosperms growing on Barro Colorado Island (BCI), Panama, onto this
      raw morphospace. This highlights that, in addition to their well-documented
      taxonomic diversity, Neotropical rainforests also represent an enormous reservoir
      of morphological diversity. Angiosperm pollen morphospace at BCI has been filled
      mostly by pollen morphotypes that are unique to single plant species. Repetition
      of pollen morphotypes among higher taxa at BCI reflects both constraint and
      convergence. This combinatorial approach to morphology addresses the complexity
      that results from large numbers of discrete character combinations and could be
      employed in any situation where organismal form can be captured by discrete
      morphological characters.

PMID- 27881757
TI  - Correction to 'High evolutionary constraints limited adaptive responses to past
      climate changes in toad skulls'.

PMID- 27881755
TI  - Unravelling Darwin's entangled bank: architecture and robustness of mutualistic
      networks with multiple interaction types.
AB  - Trying to unravel Darwin's entangled bank further, we describe the architecture
      of a network involving multiple forms of mutualism (pollination by animals, seed
      dispersal by birds and plant protection by ants) and evaluate whether this multi
      network shows evidence of a structure that promotes robustness. We found that
      species differed strongly in their contributions to the organization of the multi
      interaction network, and that only a few species contributed to the structuring
      of these patterns. Moreover, we observed that the multi-interaction networks did
      not enhance community robustness compared with each of the three independent
      mutualistic networks when analysed across a range of simulated scenarios of
      species extinction. By simulating the removal of highly interacting species, we
      observed that, overall, these species enhance network nestedness and robustness,
      but decrease modularity. We discuss how the organization of interlinked
      mutualistic networks may be essential for the maintenance of ecological
      communities, and therefore the long-term ecological and evolutionary dynamics of
      interactive, species-rich communities. We suggest that conserving these keystone
      mutualists and their interactions is crucial to the persistence of species-rich
      mutualistic assemblages, mainly because they support other species and shape the
      network organization.

PMID- 27881758
TI  - Cardiac rehabilitation following an acute coronary syndrome: Trends in referral,
      predictors and mortality outcome in a multicenter national registry between years
      2006-2013: Report from the Working Group on Cardiac Rehabilitation, the Israeli
      Heart Society.
AB  - Background Utilization of cardiac rehabilitation is suboptimal. The aim of the
      study was to assess referral trends over the past decade, to identify predictors
      for referral to a cardiac rehabilitation program, and to evaluate the association
      with one-year mortality in a large national registry of acute coronary syndrome
      patients. Design and methods Data were extracted from the Acute Coronary Syndrome
      Israeli Survey national surveys between 2006-2013. A total of 6551 patients
      discharged with a diagnosis of acute coronary syndrome were included. Results
      Referral to cardiac rehabilitation following an acute coronary syndrome increased
      from 38% in 2006 to 57% in 2013 ( p for trend < 0.001). Multivariate modeling
      identified the following independent predictors for non-referral: 2006 survey,
      older age, female sex, past stroke, heart or renal failure, prior myocardial
      infarction, minority group, and lack of in-hospital cardiac rehabilitation center
      (all p < 0.01). Kaplan-Meier survival analyses showed one-year survival rates of
      97% vs 92% in patients referred for cardiac rehabilitation as compared to those
      not referred (log-rank p < 0.01). Multivariate analysis showed that referral for
      cardiac rehabilitation was associated with a 27% mortality risk reduction at one
      year follow-up ( p = 0.03). Consistently, a 32% lower one-year mortality risk was
      evident in a propensity score matched group of 3340 patients (95% confidence
      interval 0.48-0.95, p = 0.02). Conclusions Over the past decade there was a
      significant increase in cardiac rehabilitation referral following an acute
      coronary syndrome. However, cardiac rehabilitation is still under-utilized in
      important high-risk subsets of this population. Patients referred to cardiac
      rehabilitation have a lower adjusted mortality risk.

PMID- 27881759
TI  - Effects of sea ice cover on satellite-detected primary production in the Arctic
      Ocean.
AB  - The influence of decreasing Arctic sea ice on net primary production (NPP) in the
      Arctic Ocean has been considered in multiple publications but is not well
      constrained owing to the potentially large errors in satellite algorithms. In
      particular, the Arctic Ocean is rich in coloured dissolved organic matter (CDOM)
      that interferes in the detection of chlorophyll a concentration of the standard
      algorithm, which is the primary input to NPP models. We used the quasi-analytic
      algorithm (Lee et al 2002 Appl. Opti. 41, 5755-5772. (doi:10.1364/AO.41.005755))
      that separates absorption by phytoplankton from absorption by CDOM and detrital
      matter. We merged satellite data from multiple satellite sensors and created a 19
      year time series (1997-2015) of NPP. During this period, both the estimated
      annual total and the summer monthly maximum pan-Arctic NPP increased by about
      47%. Positive monthly anomalies in NPP are highly correlated with positive
      anomalies in open water area during the summer months. Following the earlier ice
      retreat, the start of the high-productivity season has become earlier, e.g. at a
      mean rate of -3.0 d yr-1 in the northern Barents Sea, and the length of the high
      productivity period has increased from 15 days in 1998 to 62 days in 2015. While
      in some areas, the termination of the productive season has been extended, owing
      to delayed ice formation, the termination has also become earlier in other areas,
      likely owing to limited nutrients.

PMID- 27881760
TI  - Changes in composition and abundance of functional groups of arctic fungi in
      response to long-term summer warming.
AB  - We characterized fungal communities in dry and moist tundra and investigated the
      effect of long-term experimental summer warming on three aspects of functional
      groups of arctic fungi: richness, community composition and species abundance.
      Warming had profound effects on community composition, abundance, and, to a
      lesser extent, on richness of fungal functional groups. In addition, our data
      show that even within functional groups, the direction and extent of response to
      warming tend to be species-specific and we recommend that studies on fungal
      communities and their roles in nutrient cycling take into account species-level
      responses.

PMID- 27881762
TI  - Bacteria facilitate prey retention by the pitcher plant Darlingtonia californica.
AB  - Bacteria are hypothesized to provide a variety of beneficial functions to plants.
      Many carnivorous pitcher plants, for example, rely on bacteria for digestion of
      captured prey. This bacterial community may also be responsible for the low
      surface tensions commonly observed in pitcher plant digestive fluids, which might
      facilitate prey capture. I tested this hypothesis by comparing the physical
      properties of natural pitcher fluid from the pitcher plant Darlingtonia
      californica and cultured 'artificial' pitcher fluids and tested these fluids'
      prey retention capabilities. I found that cultures of pitcher leaves' bacterial
      communities had similar physical properties to raw pitcher fluids. These
      properties facilitated the retention of insects by both fluids and hint at a
      previously undescribed class of plant-microbe interaction.

PMID- 27881761
TI  - Where in the air? Aerial habitat use of nocturnally migrating birds.
AB  - The lower atmosphere (i.e. aerosphere) is critical habitat for migrant birds.
      This habitat is vast and little is known about the spatio-temporal patterns of
      distribution and abundance of migrants in it. Increased human encroachment into
      the aerosphere makes understanding where and when migratory birds use this
      airspace a key to reducing human-wildlife conflicts. We use weather surveillance
      radar to describe large-scale height distributions of nocturnally migrating birds
      and interpret these distributions as aggregate habitat selection behaviours of
      individual birds. As such, we detail wind cues that influence selection of flight
      heights. Using six radars in the eastern USA during the spring (2013-2015) and
      autumn (2013 and 2014), we found migrants tended to adjust their heights
      according to favourable wind profit. We found that migrants' flight altitudes
      correlated most closely with the altitude of maximum wind profit; however,
      absolute differences in flight heights and height of maximum wind profit were
      large. Migrants tended to fly slightly higher at inland sites compared with
      coastal sites during spring, but not during autumn. Migration activity was
      greater at coastal sites during autumn, but not during spring. This
      characterization of bird migration represents a critical advance in our
      understanding of migrant distributions in flight and a new window into habitat
      selection behaviours.

PMID- 27881763
TI  - The effects of tradition on problem solving by two wild populations of bearded
      capuchin monkeys in a probing task.
AB  - The effects of culture on individual cognition have become a core issue among
      cultural primatologists. Field studies with wild populations provide evidence on
      the role of social cues in the ontogeny of tool use in non-human primates, and on
      the transmission of such behaviours over generations through socially biased
      learning. Recent experimental studies have shown that cultural knowledge may
      influence problem solving in wild populations of chimpanzees. Here, we present
      the results from a field experiment comparing the performance of bearded capuchin
      monkeys (Sapajus libidinosus) from two wild savannah populations with distinct
      toolkits in a probing task. Only the population that already exhibited the
      customary use of probing tools succeeded in solving the new problem, suggesting
      that their cultural repertoire shaped their approach to the new task. Moreover,
      only this population, which uses stone tools in a broader range of contexts,
      tried to use them to solve the problem. Social interactions can affect the
      formation of learning sets and they affect the performance of the monkeys in
      problem solving. We suggest that behavioural traditions affect the ways non-human
      primates solve novel foraging problems using tools.

PMID- 27881764
TI  - Zebrafish embryonic development is induced by carp sperm.
AB  - Haploid gynogenetic screens increase the efficiency of forward genetic screens
      and linkage analysis in fish. Typically, UV-irradiated zebrafish sperm is used to
      activate zebrafish oocytes for haploid screens. We describe the use of UV
      irradiated common carp sperm to activate haploid gynogenetic zebrafish
      development. Carp * zebrafish hybrids are shown to have a characteristic set of
      features during embryonic development and exhibit functional development of
      several tissues (muscle, heart and nervous system). Hybrids become inviable past
      the embryonic stages. This technique eliminates the possibility of incompletely
      irradiated zebrafish spermatozoa contaminating haploid progenies. While
      developing this protocol, one unique zebrafish female was identified which, upon
      insemination with UV-irradiated carp spermatozoa, repeatedly displayed
      spontaneous diploidization of the maternal chromosomes in her offspring.

PMID- 27881765
TI  - Improved homeothermy and hypothermia in African lions during gestation.
AB  - Mammals use endogenously produced heat to maintain a high and relatively constant
      core body temperature (Tb). How they regulate their Tb during reproduction might
      inform us as to what thermal conditions are necessary for optimal development of
      offspring. However, few studies have measured Tb in free-ranging animals for
      sufficient periods of time to encounter reproductive events. We measured Tb
      continuously in six free-ranging adult female African lions (Panthera leo) for
      approximately 1 year. Lions reduced the 24 h amplitude of Tb by about 25% during
      gestation and decreased mean 24 h Tb by 1.3 +/- 0.1 degrees C over the course of
      the gestation, reducing incidences of hyperthermia (Tb > 39.5 degrees C). The
      observation of improved homeothermy during reproduction may support the parental
      care model (PCM) for the evolution of endothermy, which postulates that
      endothermy arose in birds and mammals as a consequence of more general selection
      for parental care. According to the PCM, endothermy arose because it enabled
      parents to better control incubation temperature, leading to rapid growth and
      development of offspring and thus to fitness benefits for the parents. Whether
      the precision of Tb regulation in pregnant lions, and consequently their
      reproductive success, will be influenced by changing environmental conditions,
      particularly hotter and drier periods associated with climate change, remains to
      be determined.

PMID- 27881766
TI  - Bridging the gap: parkour athletes provide new insights into locomotion
      energetics of arboreal apes.
AB  - The tree canopy is an energetically challenging environment to traverse. Along
      with compliant vegetation, gaps in the canopy can prove energetically costly if
      they force a route-extending detour. Arboreal apes exhibit diverse locomotion
      strategies, including for gap crossing. Which one they employ in any given
      scenario may be influenced by the energy costs to do so, which are affected by
      the details of the immediate environment in combination with their body size.
      Measuring energetics of arboreal apes is not tractable; thus our knowledge in
      this area is limited. We devised a novel, custom-made experimental set-up to
      record the energy expenditure of parkour athletes tree-swaying, jumping and
      vertical climbing. The latter strategy was vastly more expensive, indicating that
      when energy economy is the focus arboreal apes will prioritize routes that limit
      height changes. Whether tree-swaying or jumping was most economical for the
      athletes depended upon interactions between tree stiffness, the distance to
      cross, number of tree-sways required and their own mass. Updated analysis of
      previous interspecific correlations suggests that whether the relative costs to
      vertical climb are size-invariant across primate species is complicated by
      details of the climbing context.

PMID- 27881767
TI  - Daylight saving time can decrease the frequency of wildlife-vehicle collisions.
AB  - Daylight saving time (DST) could reduce collisions with wildlife by changing the
      timing of commuter traffic relative to the behaviour of nocturnal animals. To
      test this idea, we tracked wild koalas (Phascolarctos cinereus) in southeast
      Queensland, where koalas have declined by 80% in the last 20 years, and compared
      their movements with traffic patterns along roads where they are often killed.
      Using a simple model, we found that DST could decrease collisions with koalas by
      8% on weekdays and 11% at weekends, simply by shifting the timing of traffic
      relative to darkness. Wildlife conservation and road safety should become part of
      the debate on DST.

PMID- 27881769
TI  - Sex in Context: Limitations of Animal Studies for Addressing Human Sex/Gender
      Neurobehavioral Health Disparities.
AB  - Many brain and behavioral disorders differentially affect men and women. The new
      National Institutes of Health requirement to include both male and female animals
      in preclinical studies aims to address such health disparities, but we argue that
      the mandate is not the best solution to this problem. Sex differences are highly
      species-specific, tied to the mating system and social ecology of a given species
      or even strain of animal. In many cases, animals poorly replicate male-female
      differences in brain-related human diseases. Sex/gender disparities in human
      health have a strong sociocultural component that is intimately entangled with
      biological sex and challenging to model in animals. We support research that
      investigates sex-related variables in hypothesis-driven studies of animal brains
      and behavior. However, institutional policies that require sex analysis and give
      it special salience over other sources of biological variance can distort
      research. We caution that the costly imposition of sex analysis on nearly all
      animal research entrenches the presumption that human brain and behavioral
      differences are largely biological in origin and overlooks the potentially more
      powerful social, psychological, and cultural contributors to male-female
      neurobehavioral health gaps.

PMID- 27881768
TI  - Considering Sex as a Biological Variable Will Be Valuable for Neuroscience
      Research.
AB  - The recently implemented National Institutes of Health policy requiring that
      grant applicants consider sex as a biological variable in the design of basic and
      preclinical animal research studies has prompted considerable discussion within
      the neuroscience community. Here, we present reasons to be optimistic that this
      new policy will be valuable for neuroscience, and we suggest some ways for
      neuroscientists to think about incorporating sex as a variable in their research.

PMID- 27881770
TI  - Enhancing Remyelination through a Novel Opioid-Receptor Pathway.

PMID- 27881771
TI  - Visualizing Local Protein Synthesis and Its Modulation by FMRP and Visual
      Experience.

PMID- 27881772
TI  - Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic
      Target for Alzheimer's Disease Treatment.
AB  - : Mushroom dendritic spine structures are essential for memory storage and the
      loss of mushroom spines may explain memory defects in aging and Alzheimer's
      disease (AD). The stability of mushroom spines depends on stromal interaction
      molecule 2 (STIM2)-mediated neuronal-store-operated Ca2+ influx (nSOC) pathway,
      which is compromised in AD mouse models, in aging neurons, and in sporadic AD
      patients. Here, we demonstrate that the Transient Receptor Potential Canonical 6
      (TRPC6) and Orai2 channels form a STIM2-regulated nSOC Ca2+ channel complex in
      hippocampal mushroom spines. We further demonstrate that a known TRPC6 activator,
      hyperforin, and a novel nSOC positive modulator, NSN21778 (NSN), can stimulate
      activity of nSOC pathway in the spines and rescue mushroom spine loss in both
      presenilin and APP knock-in mouse models of AD. We further show that NSN rescues
      hippocampal long-term potentiation impairment in APP knock-in mouse model. We
      conclude that the STIM2-regulated TRPC6/Orai2 nSOC channel complex in dendritic
      mushroom spines is a new therapeutic target for the treatment of memory loss in
      aging and AD and that NSN is a potential candidate molecule for therapeutic
      intervention in brain aging and AD. SIGNIFICANCE STATEMENT: Mushroom dendritic
      spine structures are essential for memory storage and the loss of mushroom spines
      may explain memory defects in Alzheimer's disease (AD). This study demonstrated
      that Transient Receptor Potential Canonical 6 (TRPC6) and Orai2 form stromal
      interaction molecule 2 (STIM2)-regulated neuronal-store-operated Ca2+ influx
      (nSOC) channel complex in hippocampal synapse and the resulting Ca2+ influx is
      critical for long-term maintenance of mushroom spines in hippocampal neurons. A
      novel nSOC-positive modulator, NSN21778 (NSN), rescues mushroom spine loss and
      synaptic plasticity impairment in AD mice models. The TRPC6/Orai2 nSOC channel
      complex is a new therapeutic target and NSN is a potential candidate molecule for
      therapeutic intervention in brain aging and AD.

PMID- 27881774
TI  - Interactions Between SNAP-25 and Synaptotagmin-1 Are Involved in Vesicle Priming,
      Clamping Spontaneous and Stimulating Evoked Neurotransmission.
AB  - : Whether interactions between synaptotagmin-1 (syt-1) and the soluble NSF
      attachment protein receptors (SNAREs) are required during neurotransmission is
      debated. We examined five SNAP-25 mutations designed to interfere with syt-1
      interactions. One mutation, D51/E52/E55A, targeted negative charges within region
      II of the primary interface (Zhou et al., 2015); two mutations targeted region I
      (D166A and D166/E170A) and one mutation targeted both (D51/E52/E55/D166A). The
      final mutation (D186/D193A) targeted C-terminal residues not expected to interact
      with syt-1. An in vitro assay showed that the region I, region II, and region
      I+II (D51/E52/E55/D166A) mutants markedly reduced the attachment between syt-1
      and t-SNARE-carrying vesicles in the absence of phosphatidylinositol 4,5
      bisphosphate [PI(4,5)P2]. In the presence of PI(4,5)P2, vesicle attachment was
      unaffected by mutation. When expressed in Snap-25-null mouse autaptic neurons,
      region I mutations reduced the size of the readily releasable pool of vesicles,
      whereas the region II mutation reduced vesicular release probability. Combining
      both in the D51/E52/E55/D166A mutation abrogated evoked release. These data point
      to a division of labor between region I (vesicle priming) and region II (evoked
      release). Spontaneous release was disinhibited by region I mutations and found to
      correlate with defective complexin (Cpx) clamping in an in vitro fusion assay,
      pointing to an interdependent role of synaptotagmin and Cpx in release clamping.
      Mutation in region II (D51/E52/E55A) also unclamped release, but this effect
      could be overcome by synaptotagmin overexpression, arguing against an obligatory
      role in clamping. We conclude that three synaptic release functions of syt-1,
      vesicle priming, spontaneous release clamping, and evoked release triggering,
      depend on direct SNARE complex interaction. SIGNIFICANCE STATEMENT: The function
      of synaptotagmin-1 (syt-1):soluble NSF attachment protein receptor (SNARE)
      interactions during neurotransmission remains unclear. We mutated SNAP-25 within
      the recently identified region I and region II of the primary synaptotagmin:SNARE
      interface. Using in vitro assays and rescue experiments in autaptic neurons, we
      show that interactions within region II of the primary interface are necessary
      for synchronized calcium-triggered release, whereas region I is involved in
      vesicle priming. Spontaneous release was disinhibited by region I mutation and
      found to correlate with defective complexin (Cpx) clamping in vitro, pointing to
      an interdependent role of synaptotagmin and Cpx in release clamping. Therefore,
      vesicle priming, clamping spontaneous release, and eliciting evoked release are
      three different functions of syt-1 that involve different interaction modes with
      the SNARE complex.

PMID- 27881775
TI  - A Biophysical Model for Cytotoxic Cell Swelling.
AB  - : We present a dynamic biophysical model to explain neuronal swelling underlying
      cytotoxic edema in conditions of low energy supply, as observed in cerebral
      ischemia. Our model contains Hodgkin-Huxley-type ion currents, a recently
      discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active
      KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts
      changes in ion gradients and cell swelling during ischemia of various severity or
      channel blockage with realistic timescales. We theoretically substantiate
      experimental observations of chloride influx generating cytotoxic edema, while
      sodium entry alone does not. We show a tipping point of Na+/K+-ATPase
      functioning, where below cell volume rapidly increases as a function of the
      remaining pump activity, and a Gibbs-Donnan-like equilibrium state is reached.
      This precludes a return to physiological conditions even when pump strength
      returns to baseline. However, when voltage-gated sodium channels are temporarily
      blocked, cell volume and membrane potential normalize, yielding a potential
      therapeutic strategy. SIGNIFICANCE STATEMENT: Cytotoxic edema most commonly
      results from energy shortage, such as in cerebral ischemia, and refers to the
      swelling of brain cells due to the entry of water from the extracellular space.
      We show that the principle of electroneutrality explains why chloride influx is
      essential for the development of cytotoxic edema. With the help of a biophysical
      model of a single neuron, we show that a tipping point of the energy supply
      exists, below which the cell volume rapidly increases. We simulate realistic time
      courses to and reveal critical components of neuronal swelling in conditions of
      low energy supply. Furthermore, we show that, after transient blockade of the
      energy supply, cytotoxic edema may be reversed by temporary blockade of Na+
      channels.

PMID- 27881773
TI  - Novel Roles for the Insulin-Regulated Glucose Transporter-4 in Hippocampally
      Dependent Memory.
AB  - : The insulin-regulated glucose transporter-4 (GluT4) is critical for insulin-
      and contractile-mediated glucose uptake in skeletal muscle. GluT4 is also
      expressed in some hippocampal neurons, but its functional role in the brain is
      unclear. Several established molecular modulators of memory processing regulate
      hippocampal GluT4 trafficking and hippocampal memory formation is limited by both
      glucose metabolism and insulin signaling. Therefore, we hypothesized that
      hippocampal GluT4 might be involved in memory processes. Here, we show that, in
      male rats, hippocampal GluT4 translocates to the plasma membrane after memory
      training and that acute, selective intrahippocampal inhibition of GluT4-mediated
      glucose transport impaired memory acquisition, but not memory retrieval. Other
      studies have shown that prolonged systemic GluT4 blockade causes insulin
      resistance. Unexpectedly, we found that prolonged hippocampal blockade of glucose
      transport through GluT4-upregulated markers of hippocampal insulin signaling
      prevented task-associated depletion of hippocampal glucose and enhanced both
      working and short-term memory while also impairing long-term memory. These
      effects were accompanied by increased expression of hippocampal AMPA GluR1
      subunits and the neuronal GluT3, but decreased expression of hippocampal brain
      derived neurotrophic factor, consistent with impaired ability to form long-term
      memories. Our findings are the first to show the cognitive impact of brain GluT4
      modulation. They identify GluT4 as a key regulator of hippocampal memory
      processing and also suggest differential regulation of GluT4 in the hippocampus
      from that in peripheral tissues. SIGNIFICANCE STATEMENT: The role of insulin
      regulated glucose transporter-4 (GluT4) in the brain is unclear. In the current
      study, we demonstrate that GluT4 is a critical component of hippocampal memory
      processes. Memory training increased hippocampal GluT4 translocation and memory
      acquisition was impaired by GluT4 blockade. Unexpectedly, whereas long-term
      inhibition of GluT4 impaired long-term memory, short-term memory was enhanced.
      These data further our understanding of the molecular mechanisms of memory and
      have particular significance for type 2 diabetes (in which GluT4 activity in the
      periphery is impaired) and Alzheimer's disease (which is linked to impaired brain
      insulin signaling and for which type 2 diabetes is a key risk factor). Both
      diseases cause marked impairment of hippocampal memory linked to hippocampal
      hypometabolism, suggesting the possibility that brain GluT4 dysregulation may be
      one cause of cognitive impairment in these disease states.

PMID- 27881776
TI  - Time Is Not Space: Core Computations and Domain-Specific Networks for Mental
      Travels.
AB  - : Humans can consciously project themselves in the future and imagine themselves
      at different places. Do mental time travel and mental space navigation abilities
      share common cognitive and neural mechanisms? To test this, we recorded fMRI
      while participants mentally projected themselves in time or in space (e.g., 9
      years ago, in Paris) and ordered historical events from their mental perspective.
      Behavioral patterns were comparable for mental time and space and shaped by self
      projection and by the distance of historical events to the mental position of the
      self, suggesting the existence of egocentric mapping in both dimensions.
      Nonetheless, self-projection in space engaged the medial and lateral parietal
      cortices, whereas self-projection in time engaged a widespread parietofrontal
      network. Moreover, while a large distributed network was found for spatial
      distances, temporal distances specifically engaged the right inferior parietal
      cortex and the anterior insula. Across these networks, a robust overlap was only
      found in a small region of the inferior parietal lobe, adding evidence for its
      role in domain-general egocentric mapping. Our findings suggest that mental
      travel in time or space capitalizes on egocentric remapping and on distance
      computation, which are implemented in distinct dimension-specific cortical
      networks converging in inferior parietal lobe. SIGNIFICANCE STATEMENT: As humans,
      we can consciously imagine ourselves at a different time (mental time travel) or
      at a different place (mental space navigation). Are such abilities domain
      general, or are the temporal and spatial dimensions of our conscious experience
      separable? Here, we tested the hypothesis that mental time travel and mental
      space navigation required the egocentric remapping of events, including the
      estimation of their distances to the self. We report that, although both
      remapping and distance computation are foundational for the processing of the
      temporal and spatial dimensions of our conscious experience, their
      neuroanatomical implementations were clearly dissociable and engaged distinct
      parietal and parietofrontal networks for mental space navigation and mental time
      travel, respectively.

PMID- 27881779
TI  - Allergic Inflammation Leads to Neuropathic Pain via Glial Cell Activation.
AB  - : Allergic and atopic disorders have increased over the past few decades and have
      been associated with neuropsychiatric conditions, such as autism spectrum
      disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can
      occur in patients with atopic disorder; however, the relationship between
      allergic inflammation and neuropathic pain, and the underlying mechanism, remains
      to be established. We studied whether allergic inflammation affects the spinal
      nociceptive system. We found that mice with asthma, atopic dermatitis, or atopic
      diathesis had widespread and significantly more activated microglia and astroglia
      in the spinal cord than those without atopy, and displayed tactile allodynia.
      Microarray analysis of isolated microglia revealed a dysregulated phenotype
      showing upregulation of M1 macrophage markers and downregulation of M2 markers in
      atopic mice. Among the cell surface protein genes, endothelin receptor type B
      (EDNRB) was most upregulated. Immunohistochemical analysis revealed that EDNRB
      expression was enhanced in microglia and astroglia, whereas endothelin-1, an
      EDNRB ligand, was increased in serum, lungs, and epidermis of atopic mice. No
      EDNRA expression was found in the spinal cord. Expression of FBJ murine
      osteosarcoma viral oncogene homolog B was significantly higher in the dorsal horn
      neurons of asthma mice than nonatopic mice. The EDNRB antagonist BQ788 abolished
      glial and neural activation and allodynia. We found increased serum endothelin-1
      in atopic patients with myelitis and neuropathic pain, and activation of spinal
      microglia and astroglia with EDNRB upregulation in an autopsied case. These
      results suggest that allergic inflammation induces diffuse glial activation,
      influencing the nociceptive system via the EDNRB pathway. SIGNIFICANCE STATEMENT:
      The prevalence of allergic disorders has markedly increased over the past few
      decades. Allergic disorders are associated with neuropsychiatric conditions;
      however, the relationship between allergic inflammation and CNS complications is
      unknown. A peculiar myelitis presenting with persistent neuropathic pain has been
      reported in patients with allergic disorders. We studied how atopy exerts
      substantial influence on the nociceptive system. We found that mice with allergic
      disorders had severe allodynia with activated astroglia and microglia, and showed
      marked upregulation of endothelin-1 (ET-1) receptor type B (EDNRB) in the spinal
      cord. A selective EDNRB antagonist prevented allodynia and glial activation. Our
      findings suggest a novel mechanism whereby atopy induces glial activation and
      neuropathic pain via an ET-1/EDNRB pathway.

PMID- 27881778
TI  - Attentive Motion Discrimination Recruits an Area in Inferotemporal Cortex.
AB  - : Attentional selection requires the interplay of multiple brain areas.
      Theoretical accounts of selective attention predict different areas with
      different functional properties to support endogenous covert attention. To test
      these predictions, we devised a demanding attention task requiring motion
      discrimination and spatial selection and performed whole-brain imaging in macaque
      monkeys. Attention modulated the early visual cortex, motion-selective dorsal
      stream areas, the lateral intraparietal area, and the frontal eye fields. This
      pattern of activation supports early selection, feature-based, and biased
      competition attention accounts, as well as the frontoparietal theory of
      attentional control. While high-level motion-selective dorsal stream areas did
      not exhibit strong attentional modulation, ventral stream areas V4d and the
      dorsal posterior inferotemporal cortex (PITd) did. The PITd in fact was,
      consistently across task variations, the most significantly and most strongly
      attention-modulated area, even though it did not exhibit signs of motion
      selectivity. Thus the recruitment of the PITd in attention tasks involving
      different kinds of motion analysis is not predicted by any theoretical account of
      attention. These functional data, together with known anatomical connections,
      suggest a general and possibly critical role of the PITd in attentional
      selection. SIGNIFICANCE STATEMENT: Attention is the key cognitive function that
      selects sensory information relevant to the current goals, relegating other
      information to the shadows of consciousness. To better understand the neural
      mechanisms of this interplay between sensory processing and internal cognitive
      state, we must learn more about the brain areas supporting attentional selection.
      Here, to test theoretical accounts of attentional selection, we used a novel task
      requiring sustained attention to motion. We found that, surprisingly, among the
      most strongly attention-modulated areas is one that is neither selective for the
      sensory feature relevant for current goals nor one hitherto thought to be
      involved in attentional control. This discovery suggests a need for an extension
      of current theoretical accounts of the brain circuits for attentional selection.

PMID- 27881777
TI  - Temporal Profiling of Astrocyte Precursors Reveals Parallel Roles for Asef during
      Development and after Injury.
AB  - : Lineage development is a stepwise process, governed by stage-specific
      regulatory factors and associated markers. Astrocytes are one of the principle
      cell types in the CNS and the stages associated with their development remain
      very poorly defined. To identify these stages, we performed gene-expression
      profiling on astrocyte precursor populations in the spinal cord, identifying
      distinct patterns of gene induction during their development that are strongly
      correlated with human astrocytes. Validation studies identified a new cohort of
      astrocyte-associated genes during development and demonstrated their expression
      in reactive astrocytes in human white matter injury (WMI). Functional studies on
      one of these genes revealed that mice lacking Asef exhibited impaired astrocyte
      differentiation during development and repair after WMI, coupled with compromised
      blood-brain barrier integrity in the adult CNS. These studies have identified
      distinct stages of astrocyte lineage development associated with human WMI and,
      together with our functional analysis of Asef, highlight the parallels between
      astrocyte development and their reactive counterparts associated with injury.
      SIGNIFICANCE STATEMENT: Astrocytes play a central role in CNS function and
      associated diseases. Yet the mechanisms that control their development remain
      poorly defined. Using the developing mouse spinal cord as a model system, we
      identify molecular changes that occur in developing astrocytes. These molecular
      signatures are strongly correlated with human astrocyte expression profiles and
      validation in mouse spinal cord identifies a host of new genes associated with
      the astrocyte lineage. These genes are present in reactive astrocytes in human
      white matter injury, and functional studies reveal that one of these genes, Asef,
      contributes to reactive astrocyte responses after injury. These studies identify
      distinct stages of astrocyte lineage development and highlight the parallels
      between astrocyte development and their reactive counterparts associated with
      injury.

PMID- 27881782
TI  - Consolidation of Goal-Directed Action Depends on MAPK/ERK Signaling in Rodent
      Prelimbic Cortex.
AB  - : The prelimbic prefrontal cortex (PL) has consistently been found to be
      necessary for the acquisition of goal-directed actions in rodents. Nevertheless,
      the specific cellular processes underlying this learning remain unknown. We
      assessed changes in learning-related expression of mitogen-activated protein
      kinase/extracellular signal-related kinase (MAPK/ERK1/2) phosphorylation (pERK)
      in layers 2-3 and 5-6 of the anterior and posterior PL and in the population of
      neurons projecting to posterior dorsomedial striatum (pDMS), also implicated in
      goal-directed learning. Rats were given either a single session of training to
      press a lever for a pellet reward or yoked reward deliveries without instrumental
      training and assessed 5 or 60 min after training for pERK expression. Relative to
      yoked training, instrumental training produced an increase in pERK expression in
      all regions of the PL both at 5 and 60 min, and this was accompanied by an
      increase in nuclear pERK expression in the posterior PL in rats given
      instrumental training. pDMS-projecting neurons showed a transient increase in
      pERK expression in posterior layer 5-6 projection neurons after 5 min, and a
      delayed increase in anterior layer 2-3 neurons after 60 min, suggesting that ERK
      expression in the PL is necessary for the consolidation of goal-directed
      learning. Consistent with this claim, we found that rats trained on two lever
      press actions for distinct outcomes and then infused with the MEK inhibitor
      PD98059 into the PL immediately after training failed to acquire specific action
      outcome associations, suggesting that persistent pERK signaling in the PL is
      necessary for goal-directed learning. SIGNIFICANCE STATEMENT: The prelimbic
      cortex is implicated in goal-directed learning in rodents; however, it is unclear
      whether it is involved in the consolidation of this learning, and what cellular
      processes are involved. We used pERK as a marker of activity-related synaptic
      plasticity to assess learning-induced changes in distinct layers and neuronal
      populations of the prelimbic prefrontal cortex (PL). Training produced long
      lasting upregulation of pERK throughout the PL and specifically within neurons
      that project to the pDMS, another region critical for goal-directed learning.
      Next, we demonstrated that pERK signaling in the PL was necessary for the
      consolidation of goal-directed learning. Together, these results indicate that
      instrumental training induces ERK signaling in distinct layers and populations in
      the PL and this signaling underlies the consolidation of goal-directed learning.

PMID- 27881780
TI  - Negative Allosteric Modulation of mGluR5 Partially Corrects Pathophysiology in a
      Mouse Model of Rett Syndrome.
AB  - : Rett syndrome (RTT) is caused by mutations in the gene encoding methyl-CpG
      binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here,
      we report a test of the hypothesis of shared pathophysiology of RTT and fragile
      X, another monogenic cause of autism and intellectual disability. In fragile X,
      the loss of the mRNA translational repressor FMRP leads to exaggerated protein
      synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that
      mGluR5- and protein-synthesis-dependent synaptic plasticity were similarly
      altered in area CA1 of Mecp2 KO mice. CA1 pyramidal cell-type-specific, genome
      wide profiling of ribosome-bound mRNAs was performed in wild-type and Mecp2 KO
      hippocampal CA1 neurons to reveal the MeCP2-regulated "translatome." We found
      significant overlap between ribosome-bound transcripts overexpressed in the Mecp2
      KO and FMRP mRNA targets. These tended to encode long genes that were
      functionally related to either cytoskeleton organization or the development of
      neuronal connectivity. In the Fmr1 KO mouse, chronic treatment with mGluR5
      negative allosteric modulators (NAMs) has been shown to ameliorate many mutant
      phenotypes by correcting excessive protein synthesis. In Mecp2 KO mice, we found
      that mGluR5 NAM treatment significantly reduced the level of overexpressed
      ribosome-associated transcripts, particularly those that were also FMRP targets.
      Some Rett phenotypes were also ameliorated by treatment, most notably hippocampal
      cell size and lifespan. Together, these results suggest a potential mechanistic
      link between MeCP2-mediated transcription regulation and mGluR5/FMRP-mediated
      protein translation regulation through coregulation of a subset of genes relevant
      to synaptic functions. SIGNIFICANCE STATEMENT: Altered regulation of synaptic
      protein synthesis has been hypothesized to contribute to the pathophysiology that
      underlies multiple forms of intellectual disability and autism spectrum disorder.
      Here, we show in a mouse model of Rett syndrome (Mecp2 KO) that metabotropic
      glutamate receptor 5 (mGluR5)- and protein-synthesis-dependent synaptic
      plasticity are abnormal in the hippocampus. We found that a subset of ribosome
      bound mRNAs was aberrantly upregulated in hippocampal CA1 neurons of Mecp2 KO
      mice, that these significantly overlapped with FMRP direct targets and/or SFARI
      human autism genes, and that chronic treatment of Mecp2 KO mice with an mGluR5
      negative allosteric modulator tunes down upregulated ribosome-bound mRNAs and
      partially improves mutant mice phenotypes.

PMID- 27881781
TI  - Blocking the Interaction between EphB2 and ADDLs by a Small Peptide Rescues
      Impaired Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's
      Disease.
AB  - : Soluble amyloid-beta (Abeta) oligomers, also known as Abeta-derived diffusible
      ligands (ADDLs), are thought to be the key pathogenic factor in Alzheimer's
      disease (AD), but there is still no effective treatment for preventing or
      reversing the progression of the disease. Targeting NMDA receptor trafficking and
      regulation is a new strategy for early treatment of AD. Abeta oligomers have been
      found to bind to the fibronectin (FN) type III repeat domain of EphB2 to trigger
      EphB2 degradation, thereby impairing the normal functioning of NMDA receptors and
      resulting in cognitive deficits. Here, we identified for the first time the
      interaction sites of the EphB2 FN domain with ADDLs by applying the peptide array
      method to design and synthesize four candidate peptides (Pep21, Pep25, Pep32, and
      Pep63) that might be able to block the EphB2-ADDL interaction. Among them, Pep63
      was found to be the most effective at inhibiting the binding between EphB2 and
      ADDLs. We found that Pep63 not only rescued the ADDL-induced depletion of EphB2-
      and GluN2B-containing NMDA receptors from the neuronal surface in cultured
      hippocampal neurons, but also improved impaired memory deficits in APPswe/PS1dE9
      (APP/PS1) transgenic mice and the phosphorylation and surface expression of
      GluN2B-containing NMDA receptors in cultures. Together, these results suggest
      that blocking the EphB2-ADDL interaction by small interfering peptides may be a
      promising strategy for AD treatment. SIGNIFICANCE STATEMENT: Alzheimer's disease
      (AD) is an age-dependent neurodegenerative disorder and amyloid beta-derived
      diffusible ligands (ADDLs) play a key role in triggering the early cognitive
      deficits that constitute AD. ADDLs may bind EphB2 and alter NMDA receptor
      trafficking and synaptic plasticity. Here, we identified the interaction sites of
      the EphB2 FN domain with ADDLs for the first time to develop a small (10 aa)
      peptide (Pep63) capable of blocking the EphB2-ADDL interaction. We found that
      Pep63 not only rescued the ADDL-induced depletion of EphB2 and GluN2B-containing
      NMDA receptors from the neuronal surface in cultured hippocampal neurons, but
      also improved impaired memory deficits in APPswe/PS1dE9 (APP/PS1) transgenic
      mice. Our results suggest that blocking the EphB2-ADDL interaction with Pep63 may
      be a promising strategy for AD treatment.

PMID- 27881783
TI  - Multivariate Brain Prediction of Heart Rate and Skin Conductance Responses to
      Social Threat.
AB  - : Psychosocial stressors induce autonomic nervous system (ANS) responses in
      multiple body systems that are linked to health risks. Much work has focused on
      the common effects of stress, but ANS responses in different body systems are
      dissociable and may result from distinct patterns of cortical-subcortical
      interactions. Here, we used machine learning to develop multivariate patterns of
      fMRI activity predictive of heart rate (HR) and skin conductance level (SCL)
      responses during social threat in humans (N = 18). Overall, brain patterns
      predicted both HR and SCL in cross-validated analyses successfully (rHR = 0.54,
      rSCL = 0.58, both p < 0.0001). These patterns partly reflected central stress
      mechanisms common to both responses because each pattern predicted the other
      signal to some degree (rHR->SCL = 0.21 and rSCL->HR = 0.22, both p < 0.01), but
      they were largely physiological response specific. Both patterns included
      positive predictive weights in dorsal anterior cingulate and cerebellum and
      negative weights in ventromedial PFC and local pattern similarity analyses within
      these regions suggested that they encode common central stress mechanisms.
      However, the predictive maps and searchlight analysis suggested that the patterns
      predictive of HR and SCL were substantially different across most of the brain,
      including significant differences in ventromedial PFC, insula, lateral PFC, pre
      SMA, and dmPFC. Overall, the results indicate that specific patterns of cerebral
      activity track threat-induced autonomic responses in specific body systems.
      Physiological measures of threat are not interchangeable, but rather reflect
      specific interactions among brain systems. SIGNIFICANCE STATEMENT: We show that
      threat-induced increases in heart rate and skin conductance share some common
      representations in the brain, located mainly in the vmPFC, temporal and
      parahippocampal cortices, thalamus, and brainstem. However, despite these
      similarities, the brain patterns that predict these two autonomic responses are
      largely distinct. This evidence for largely output-measure-specific regulation of
      autonomic responses argues against a common system hypothesis and provides
      evidence that different autonomic measures reflect distinct, measurable patterns
      of cortical-subcortical interactions.

PMID- 27881784
TI  - Low Somatic Sodium Conductance Enhances Action Potential Precision in Time-Coding
      Auditory Neurons.
AB  - : Auditory nerve fibers encode sounds in the precise timing of action potentials
      (APs), which is used for such computations as sound localization. Timing
      information is relayed through several cell types in the auditory brainstem that
      share an unusual property: their APs are not overshooting, suggesting that the
      cells have very low somatic sodium conductance (gNa). However, it is not clear
      how gNa influences temporal precision. We addressed this by comparing bushy cells
      (BCs) in the mouse cochlear nucleus with T-stellate cells (SCs), which do have
      normal overshooting APs. BCs play a central role in both relaying and refining
      precise timing information from the auditory nerve, whereas SCs discard precise
      timing information and encode the envelope of sound amplitude. Nucleated-patch
      recording at near-physiological temperature indicated that the Na current density
      was 62% lower in BCs, and the voltage dependence of gNa inactivation was 13 mV
      hyperpolarized compared with SCs. We endowed BCs with SC-like gNa using two
      electrode dynamic clamp and found that synaptic activity at physiologically
      relevant rates elicited APs with significantly lower probability, through
      increased activation of delayed rectifier channels. In addition, for two near
      simultaneous synaptic inputs, the window of coincidence detection widened
      significantly with increasing gNa, indicating that refinement of temporal
      information by BCs is degraded by gNa Thus, reduced somatic gNa appears to be an
      adaption for enhancing fidelity and precision in time-coding neurons.
      SIGNIFICANCE STATEMENT: Proper hearing depends on analyzing temporal aspects of
      sounds with high precision. Auditory neurons that specialize in precise temporal
      information have a suite of unusual intrinsic properties, including
      nonovershooting action potentials and few sodium channels in the soma. However,
      it was not clear how low sodium channel availability in the soma influenced the
      temporal precision of action potentials initiated in the axon initial segment. We
      studied this using dynamic clamp to mimic sodium channels in the soma, which
      yielded normal, overshooting action potentials. Increasing somatic sodium
      conductance had major negative consequences: synaptic activity evoked action
      potentials with lower fidelity, and the precision of coincidence detection was
      degraded. Thus, low somatic sodium channel availability appears to enhance
      fidelity and temporal precision.

PMID- 27881785
TI  - Attenuation of Responses to Self-Generated Sounds in Auditory Cortical Neurons.
AB  - : Many of the sounds that we perceive are caused by our own actions, for example
      when speaking or moving, and must be distinguished from sounds caused by external
      events. Studies using macroscopic measurements of brain activity in human
      subjects have consistently shown that responses to self-generated sounds are
      attenuated in amplitude. However, the underlying manifestation of this phenomenon
      at the cellular level is not well understood. To address this, we recorded the
      activity of neurons in the auditory cortex of mice in response to sounds
      generated by their own behavior. We found that the responses of auditory cortical
      neurons to these self-generated sounds were consistently attenuated, compared
      with the same sounds generated independently of the animals' behavior. This
      effect was observed in both putative pyramidal neurons and in interneurons and
      was stronger in lower layers of auditory cortex. Downstream of the auditory
      cortex, we found that responses of hippocampal neurons to self-generated sounds
      were almost entirely suppressed. Responses to self-generated optogenetic
      stimulation of auditory thalamocortical terminals were also attenuated,
      suggesting a cortical contribution to this effect. Further analyses revealed that
      the attenuation of self-generated sounds was not simply due to the nonspecific
      effects of movement or behavioral state on auditory responsiveness. However, the
      strength of attenuation depended on the degree to which self-generated sounds
      were expected to occur, in a cell-type-specific manner. Together, these results
      reveal the cellular basis underlying attenuated responses to self-generated
      sounds and suggest that predictive processes contribute to this effect.
      SIGNIFICANCE STATEMENT: Distinguishing self-generated from externally generated
      sensory input poses a fundamental problem for behaving organisms. Our study in
      mice shows for the first time that responses of auditory cortical neurons are
      attenuated to sounds generated manually by the animals' own behavior. This effect
      is distinct from the nonspecific effect of behavioral activity on auditory
      responsiveness that has previously been reported and its magnitude is modulated
      by the probability with which self-generated sounds occur, suggesting an
      underlying predictive process. We also reveal how this effect varies across cell
      types and cortical layers. These findings lay a foundation for studying
      impairments in the processing of self-generated sounds, which are observed in
      psychiatric illness, in animal disease models.

PMID- 27881787
TI  - Sensory and Working Memory Representations of Small and Large Numerosities in the
      Crow Endbrain.
AB  - : Neurons in the avian nidopallium caudolaterale (NCL), an endbrain structure
      that originated independently from the mammalian neocortex, process visual
      numerosities. To clarify the code for number in this anatomically distinct
      endbrain area in birds, neuronal responses to a broad range of numerosities were
      analyzed. We recorded single-neuron activity from the NCL of crows performing a
      delayed match-to-sample task with visual numerosities as discriminanda. The
      responses of >20% of randomly selected neurons were modulated significantly by
      numerosities ranging from one to 30 items. Numerosity-selective neurons showed
      bell-shaped tuning curves with one of the presented numerosities as preferred
      numerosity regardless of the physical appearance of the items. The resulting
      labeled-line code exhibited logarithmic compression obeying the Weber-Fechner law
      for magnitudes. Comparable proportions of selective neurons were found, not only
      during stimulus presentation, but also in the delay phase, indicating a dominant
      role of the NCL in numerical working memory. Both during sensory encoding and
      memorization of numerosities in working memory, NCL activity predicted the crows'
      number discrimination performance. These neuronal data reveal striking
      similarities across vertebrate taxa in their code for number despite convergently
      evolved and anatomically distinct endbrain structures. SIGNIFICANCE STATEMENT:
      Birds are known for their capabilities to process numerical quantity. However,
      birds lack a six-layered neocortex that enables primates with numerical
      competence. We aimed to decipher the neuronal code for numerical quantity in the
      independently and distinctly evolved endbrain of birds. We recorded the activity
      of neurons in an endbrain association area termed nidopallium caudolaterale (NCL)
      from crows that assessed and briefly memorized numerosities from one to 30 dots.
      We report a neuronal code for sensory representation and working memory of
      numerosities in the crow NCL exhibiting several characteristics that are
      surprisingly similar to the ones found in primates. Our data suggest a common
      code for number in two different vertebrate taxa that has evolved based on
      convergent evolution.

PMID- 27881789
TI  - Correction: Utevsky et al., "Precuneus Is a Functional Core of the Default-Mode
      Network".

PMID- 27881788
TI  - Brain Network Mechanisms Underlying Motor Enhancement by Transcranial Entrainment
      of Gamma Oscillations.
AB  - : Gamma and beta oscillations are routinely observed in motor-related brain
      circuits during movement preparation and execution. Entrainment of gamma or beta
      oscillations via transcranial alternating current stimulation (tACS) over primary
      motor cortex (M1) has opposite effects on motor performance, suggesting a causal
      role of these brain rhythms for motor control. However, it is largely unknown
      which brain mechanisms characterize these changes in motor performance brought
      about by tACS. In particular, it is unclear whether these effects result from
      brain activity changes only in the targeted areas or within functionally
      connected brain circuits. Here we investigated this issue by applying gamma-band
      and beta-band tACS over M1 in healthy humans during a visuomotor task and
      concurrent functional magnetic resonance imaging (fMRI). Gamma tACS indeed
      improved both the velocity and acceleration of visually triggered movements,
      compared with both beta tACS and sham stimulation. Beta tACS induced a numerical
      decrease in velocity compared with sham stimulation, but this was not
      statistically significant. Crucially, gamma tACS induced motor performance
      enhancements correlated with changed BOLD activity in the stimulated M1.
      Moreover, we found frequency- and task-specific neural compensatory activity
      modulations in the dorsomedial prefrontal cortex (dmPFC), suggesting a key
      regulatory role of this region in motor performance. Connectivity analyses
      revealed that the dmPFC interacted functionally with M1 and with regions within
      the executive motor system. These results suggest a role of the dmPFC for motor
      control and show that tACS-induced behavioral changes not only result from
      activity modulations underneath the stimulation electrode but also reflect
      compensatory modulation within connected and functionally related brain networks.
      More generally, our results illustrate how combined tACS-fMRI can be used to
      resolve the causal link between cortical rhythms, brain systems, and behavior.
      SIGNIFICANCE STATEMENT: Recent research has suggested a causal role for gamma
      oscillations during movement preparation and execution. Here we combine
      transcranial alternating current stimulation (tACS) with functional magnetic
      resonance imaging (fMRI) to identify the neural mechanisms that accompany motor
      performance enhancements triggered by gamma tACS over the primary motor cortex.
      We show that the tACS-induced motor performance enhancements correlate with
      changed neural activity in the stimulated area and modulate, in a frequency- and
      task-specific manner, the neural activity in the dorsomedial prefrontal cortex.
      This suggests a regulatory role of this region for motor control. More generally,
      we show that combined tACS-fMRI can elucidate the causal link between brain
      oscillations, neural systems, and behavior.

PMID- 27881786
TI  - Neuronal Dysfunction in iPSC-Derived Medium Spiny Neurons from Chorea
      Acanthocytosis Patients Is Reversed by Src Kinase Inhibition and F-Actin
      Stabilization.
AB  - : Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by
      red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell
      membrane disturbances based on depolymerized cortical actin and an elevated Lyn
      kinase activity in erythrocytes from ChAc patients were identified. How this
      contributes to the mechanism of neurodegeneration is still unknown. To gain
      insight into the pathophysiology, we established a ChAc patient-derived induced
      pluripotent stem cell model and an efficient differentiation protocol providing a
      large population of human striatal medium spiny neurons (MSNs), the main target
      of neurodegeneration in ChAc. Patient-derived MSNs displayed enhanced neurite
      outgrowth and ramification, whereas synaptic density was similar to controls.
      Electrophysiological analysis revealed a pathologically elevated synaptic
      activity in ChAc MSNs. Treatment with the F-actin stabilizer phallacidin or the
      Src kinase inhibitor PP2 resulted in the significant reduction of disinhibited
      synaptic currents to healthy control levels, suggesting a Src kinase- and actin
      dependent mechanism. This was underlined by increased G/F-actin ratios and
      elevated Lyn kinase activity in patient-derived MSNs. These data indicate that F
      actin stabilization and Src kinase inhibition represent potential therapeutic
      targets in ChAc that may restore neuronal function. SIGNIFICANCE STATEMENT:
      Chorea-acanthocytosis (ChAc) is a fatal neurodegenerative disease without a known
      cure. To gain pathophysiological insight, we newly established a human in vitro
      model using skin biopsies from ChAc patients to generate disease-specific induced
      pluripotent stem cells (iPSCs) and developed an efficient iPSC differentiation
      protocol providing striatal medium spiny neurons. Using patch-clamp
      electrophysiology, we detected a pathologically enhanced synaptic activity in
      ChAc neurons. Healthy control levels of synaptic activity could be restored by
      treatment of ChAc neurons with the F-actin stabilizer phallacidin and the Src
      kinase inhibitor PP2. Because Src kinases are involved in bridging the membrane
      to the actin cytoskeleton by membrane protein phosphorylation, our data suggest
      an actin-dependent mechanism of this dysfunctional phenotype and potential
      treatment targets in ChAc.

PMID- 27881791
TI  - Measuring Substance Use Among System-Involved IPV Survivors: A Research Note.
AB  - This research note presents findings from a qualitative study exploring female,
      system-involved intimate partner violence (IPV) survivors' perspectives on
      substance use disclosure in the context of research studies. The study sample
      includes 22 women who completed a court- and/or child protective services (CPS)
      mandated IPV parenting program. Analyses revealed three key areas of
      participants' perspectives on substance use assessment and disclosure: (a)
      administration setting/format and measurement clarity, (b) administrator
      characteristics, and (c) repercussions due to breach of confidentiality. Findings
      from the current study offer insights into barriers for survivors reporting their
      substance use and suggestions for researchers seeking to assess substance use
      among this population.

PMID- 27881792
TI  - ESTIMATES OF RADIATION DOSES TO THE SKIN FOR PEOPLE CAMPED AT WALLATINNA DURING
      THE UK TOTEM 1 ATOMIC WEAPONS TEST.
AB  - A group of Aboriginal people was camped at Wallatinna in South Australia, ~170 km
      downwind from Emu Field, where an atomic test (the Totem 1 test) was carried out
      at 07.00 on 15 October 1953 local time (21.30 on 14 October 1953 GMT (Greenwich
      Mean Time)). They left the camp ~24 hours later. These people stated that a
      phenomenon that has become known as a 'black mist' rolled through their camp site
      ~5 hours after detonation and that some of them subsequently became sick,
      displaying skin reddening and nausea. They feared that the sickness was a result
      of exposure to high levels of radiation. The purpose of this paper is to
      determine if these people could have received ionising radiation doses high
      enough to cause the symptoms displayed. The methodology used for the dose
      estimates is described in the paper. The exposure modes considered were external
      exposure due to the passage of a contaminated plume over the camp site,
      inhalation of material from this plume, external exposure from material deposited
      on the ground as the plume passed, and consumption of contaminated food and
      water. The contaminants considered in the airborne cloud and the ground plume
      were fission products and unburnt plutonium from the nuclear detonation, and
      neutron activation products caused by vaporisation of the tower used to position
      the weapon. The source was approximated by a line source. An upper estimate of
      the effective doses received is ~4 mSv, which is well below the level at which
      acute radiation effects are observed. This estimate is consistent with earlier
      assessments, which did not consider inhalation of the contribution from neutron
      activation products.

PMID- 27881793
TI  - A cytogenetic biomonitoring of industrial radiographers occupationally exposed to
      low levels of ionizing radiation by using cbmn assay.
AB  - Industrial radiography is the process of using either gamma-emitting radionuclide
      sources or X-ray machines to examine the safety of industrial materials. The
      average annual effective dose in industrial radiography is one of the highest
      among radiation workers. The aim of this study was to investigate the cytogenetic
      effects of ionizing radiation in the peripheral blood lymphocytes of 60
      industrial radiographers and 40 non-exposed individuals as the control group by
      using cytokinesis-block micronucleus (CBMN) assay. Totally, the frequencies of
      micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) were
      significantly higher in the industrial radiographers than in the controls (p =
      0.000). The mean MN frequency per 1000 binucleated cells in the industrial
      radiographers with last 5-y radiation dose of >100 mSv was significantly higher
      than those with <=100 mSv (34.81 +/- 12.70/00 vs. 26.33 +/- 7.940/00, p = 0.024).
      The effect of age was observed in the control group and subjects with the age of
      >30 y showed significantly higher MN frequency compared with the subjects with
      the age of <=30 y (9.45 +/- 3.710/00 vs. 6.81 +/- 3.050/00, p = 0.02). No obvious
      trend of increased MN as a function of either duration of employment or age or
      smoking status was observed in the industrial radiographers. The results show the
      increased levels of cytogenetic damages in the industrial radiographers. Even the
      workers exposed to the permissible doses are subjected to elevated frequencies of
      DNA damages. These findings confirm the importance of cytogenetic biomonitoring
      program beside physical dosimetry, surveying radiation safety of equipment and
      periodic training of workers for improvement of safety and radiation protection.

PMID- 27881794
TI  - First Map of Residential Indoor Radon Measurements in Azerbaijan.
AB  - This article describes results of the first measurements of indoor radon
      concentrations in Azerbaijan, including description of the methodology and the
      mathematical and statistical processing of the results obtained. Measured radon
      concentrations varied considerably: from almost radon-free houses to around 1100
      Bq m-3. However, only ~7% of the total number of measurements exceeded the
      maximum permissible concentrations. Based on these data, maps of the distribution
      of volumetric activity and elevated indoor radon concentrations in Azerbaijan
      were created. These maps reflect a mosaic character of distribution of radon and
      enhanced values that are confined to seismically active areas at the intersection
      of an active West Caspian fault with sub-latitudinal faults along the Great and
      Lesser Caucasus and the Talysh mountains. Spatial correlation of radon and
      temperature behavior is also described. The data gathered on residential indoor
      radon have been integrated into the European Indoor Radon Map.

PMID- 27881796
TI  - Isolated digital necrotizing fasciitis: an unusual presentation.

PMID- 27881795
TI  - Microdosimetric Measurements in Gamma and neutron Fields with a Tissue Equivalent
      Proportional Counter Based on a Gas Electron Multiplier.
AB  - A multi-element tissue-equivalent proportional counter (TEPC), based on a single
      gas electron multiplier (GEM) foil of standard geometry, has been constructed
      with 16 cylindrical sensitives volumes. In this article, the design of this novel
      counter is described and first microdosimetric measurements are presented. To
      study the response of the GEM-TEPC to both low and high linear energy transfer
      radiation fields, the microdosimetric spectra due to a 137Cs gamma-ray source and
      to fast neutrons from 7Li(d,n)8Be reaction have been measured using pure propane
      gas at low pressure, in order to simulate a tissue site of about 1 um equivalent
      size. The comparison with spectra measured with a spherical TEPC and with a mini
      TEPC demonstrates promising properties for application of the GEM-TEPC for
      microdosimetric applications.

PMID- 27881797
TI  - Deterioration of Vestibular Cells in Labyrinthitis.
AB  - OBJECTIVE: To quantitatively assess the effect of serous labyrinthitis,
      suppurative labyrinthitis, and labyrinthitis ossificans on vestibular hair cells,
      dark cells, and transitional cells. METHODS: We examined human temporal bone
      specimens with serous labyrinthitis, suppurative labyrinthitis, and labyrinthitis
      ossificans, then compared them with age-matched control groups without
      labyrinthitis. We evaluated the density of type I and II vestibular hair cells,
      dark cells, and transitional cells in the peripheral sensorial organs. RESULTS:
      The mean density of type I vestibular hair cells in the maculae of the saccule
      significantly differed between the serous labyrinthitis group and its control
      group. The loss of type I and II vestibular hair cells in all of the peripheral
      sensorial organs was significantly higher in the suppurative labyrinthitis group
      than in its control group. The mean density of dark cells in the lateral and
      posterior semicircular canals was significantly lower in the suppurative
      labyrinthitis group than in its control group. The mean density of type I and II
      vestibular hair cells, dark cells, and transitional cells was significantly lower
      in the labyrinthitis ossificans group than in its control group. CONCLUSION: The
      loss of vestibular hair cells and degenerative changes in dark cells and
      transitional cells could affect vestibular function in patients with
      labyrinthitis.

PMID- 27881798
TI  - Acclimation of leaf water status and stem hydraulics to drought and tree
      neighbourhood: alternative strategies among the saplings of five temperate
      deciduous tree species.
AB  - Adjustment in leaf water status parameters and modification in xylem structure
      and functioning can be important elements of a tree's response to continued water
      limitation. In a growth trial with saplings of five co-occurring temperate broad
      leaved tree species (genera Fraxinus, Acer, Carpinus, Tilia and Fagus) conducted
      in moist or dry soil, we compared the drought acclimation in several leaf water
      status and stem hydraulic parameters. Considering the extremes in the species
      responses, Fraxinus excelsior L. improved its leaf tissue hydration in the dry
      treatment through osmotic, elastic and apoplastic adjustment while Fagus
      sylvatica L. solely modified its xylem anatomy, which resulted in increased
      embolism resistance at the cost of hydraulic efficiency. Our results demonstrate
      the contrasting response strategies of coexisting tree species and how variable
      trait plasticity among species can be. The comparison of plants grown either in
      monoculture or in five-species mixture showed that the neighbouring species
      diversity can significantly influence a tree's hydraulic architecture and leaf
      water status regulation. Droughted Carpinus betulus L. (and to a lesser extent,
      Acer pseudoplatanus L.) plants developed a more efficient stem hydraulic system
      in heterospecific neighbourhoods, while that of F. sylvatica was generally more
      efficient in conspecific than heterospecific neighbourhoods. We conclude that co
      occurring tree species may develop a high diversity of drought-response
      strategies, and exploring the full diversity of trait characteristics requires
      synchronous study of acclimation at the leaf and stem (and possibly also the
      root) levels, and consideration of physiological as well as morphological and
      anatomical modifications.

PMID- 27881799
TI  - Water-deficit and fungal infection can differentially affect the production of
      different classes of defense compounds in two host pines of mountain pine beetle.
AB  - Bark beetles are important agents of tree mortality in conifer forests and their
      interaction with trees is influenced by host defense chemicals, such as
      monoterpenes and phenolics. Since mountain pine beetle (Dendroctonus ponderosae
      Hopkins) has expanded its host range from lodgepole pine (Pinus contorta Doug. ex
      Loud. (var. latifolia Engelm.))-dominated forests to the novel jack pine (Pinus
      banksiana Lamb.) forests in western Canada, studies investigating the jack pine
      suitability as a host for this beetle have exclusively focused on monoterpenes,
      and whether phenolics affect jack pine suitability to mountain pine beetle and
      its symbiotic fungus Grosmannia clavigera is unknown. We investigated the
      phenolic and monoterpene composition in phloem and foliage of jack and lodgepole
      pines, and their subsequent change in response to water deficit and G. clavigera
      inoculation treatments. In lodgepole pine phloem, water deficit treatment
      inhibited the accumulation of both the total and richness of phenolics, but had
      no effect on total monoterpene production or richness. Fungal infection also
      inhibited the total phenolic production and had no effect on phenolic or
      monoterpene richness, but increased total monoterpene synthesis by 71%. In jack
      pine phloem, water deficit treatment reduced phenolic production, but had no
      effect on phenolic or monoterpene richness or total monoterpenes. Fungal
      infection did not affect phenolic or monoterpene production. Lesions of both
      species contained lower phenolics but higher monoterpenes than non-infected
      phloem in the same tree. In both species, richness of monoterpenes and phenolics
      was greater in non-infected phloem than in lesions. We conclude that monoterpenes
      seem to be a critical component of induced defenses against G. clavigera in both
      jack and lodgepole pines; however, a lack of increased monoterpene response to
      fungal infection is an important evolutionary factor defining jack pine
      suitability to the mountain pine beetle invasion in western Canada.

PMID- 27881800
TI  - Genetic stability of physiological responses to defoliation in a eucalypt and
      altered chemical defence in regrowth foliage.
AB  - Defoliation may initiate physiological recovery and chemical defence mechanisms
      that allow a plant to improve fitness after damage. Such responses may result in
      changes in plant resource allocation that influence growth and foliar chemistry.
      In this study, we investigated the nature and stability of the defoliation
      response of juvenile plants from three divergent populations of Eucalyptus
      globulus Labill. A partial defoliation treatment that removed all upper crown
      leaves and the apical buds was applied to plants sourced from eight families from
      each of three populations representing contrasting chemical resistance to
      mammalian herbivory. Growth, photosynthetic rate and chlorophyll content were
      assessed pre-defoliation and periodically up to 12 weeks post-defoliation. The
      content of key plant primary and secondary metabolites was assessed pre
      defoliation, at 12 weeks post-defoliation in the old foliage (positioned below
      the point of defoliation) and in the new foliage of the control plants and
      regrowth (from axillary buds) on the defoliated plants. There were clear
      treatment impacts on physiological responses, growth and foliar chemical traits,
      but despite significant constitutive differences in physiology, growth and
      chemistry the three E. globulus populations did not vary in their response to
      foliage loss. Distinct physiological responses to defoliation were observed with
      treatment plants showing significant up-regulation of photosynthetic rate and
      increased chlorophyll content in the old foliage remaining in the lower crown.
      There was a significant increase in the concentrations of a number of foliar
      chemical compounds in the regrowth arising from previously dormant axillary buds
      compared with new growth derived from apical meristems. There were changes in
      biomass allocation; defoliated plants had increased branching and leaf biomass,
      with changes in regrowth morphology to increase light capture. This study argues
      for multiple responses of E. globulus juveniles to defoliation involving apical
      bud loss, including elevated chemical defences matched with increased growth.
      From a chemical defence perspective, these responses create an enhanced chemical
      mosaic to the herbivore, with leaves remaining after partial browsing potentially
      being more palatable than the regrowth. This study demonstrates the multiple
      independent strategies plants may use to respond to partial defoliation and
      emphasizes the dynamic interplay between growth and defence in the recovery
      response.

PMID- 27881801
TI  - (In)validating experimentally derived knowledge about influenza A defective
      interfering particles.
AB  - A defective interfering particle (DIP) in the context of influenza A virus is a
      virion with a significantly shortened RNA segment substituting one of eight full
      length parent RNA segments, such that it is preferentially amplified. Hence, a
      cell co-infected with DIPs will produce mainly DIPs, suppressing infectious virus
      yields and affecting infection kinetics. Unfortunately, the quantification of
      DIPs contained in a sample is difficult because they are indistinguishable from
      standard virus (STV). Using a mathematical model, we investigated the standard
      experimental method for counting DIPs based on the reduction in STV yield
      (Bellett & Cooper, 1959, Journal of General Microbiology 21, 498-509
      (doi:10.1099/00221287-21-3-498)). We found the method is valid for counting DIPs
      provided that: (i) an STV-infected cell's co-infection window is approximately
      half its eclipse phase (it blocks infection by other virions before it begins
      producing progeny virions), (ii) a cell co-infected by STV and DIP produces less
      than 1 STV per 1000 DIPs and (iii) a high MOI of STV stock (more than 4 PFU per
      cell) is added to perform the assay. Prior work makes no mention of these
      criteria such that the method has been applied incorrectly in several
      publications discussed herein. We determined influenza A virus meets these
      criteria, making the method suitable for counting influenza A DIPs.

PMID- 27881802
TI  - Elongated magnetite nanoparticle formation from a solid ferrous precursor in a
      magnetotactic bacterium.
AB  - Magnetotactic bacteria are aquatic microorganisms that intracellularly mineralize
      ferrimagnetic nanoparticles enabling the cells to align with the geomagnetic
      field. The bacteria produce a magnetic mineral of species-specific phase
      (magnetite Fe(II)Fe(III)2O4 or greigite Fe(II)Fe(III)2S4), size, morphology and
      particle assembly. Several species produce crystals of unusual elongated particle
      shapes, which break the symmetry of the thermodynamically favoured isometric
      morphology. Such morphologies are thought to affect domain size and orientation
      of the internal magnetization. Therefore, they are interesting study objects to
      develop new synthetic strategies for the morphological control of nanoparticles.
      We investigate the formation of such irregularly shaped nanomagnets in the
      species Desulfovibrio magneticus RS-1. In contrast to previously described
      organisms, this bacterium accumulates iron predominantly as Fe(II) rather than
      Fe(III) consistent with an alternative oxidative biomineralization route.
      Further, using high-resolution electron microscopy, we observe an epitaxial
      relationship between precursor and the final mineral phase supporting the notion
      of a solid-state transformation pathway. The precursor is likely a green rust
      previously thought to convert to magnetite only by dissolution and re
      precipitation. Our findings represent a novel observation in the interconversion
      of iron (oxyhydr)oxide materials and suggest that solid-state growth processes
      could be required to produce irregularly shaped, elongated magnetite
      nanocrystals.

PMID- 27881803
TI  - Inferring animal social networks and leadership: applications for passive
      monitoring arrays.
AB  - Analyses of animal social networks have frequently benefited from techniques
      derived from other disciplines. Recently, machine learning algorithms have been
      adopted to infer social associations from time-series data gathered using remote,
      telemetry systems situated at provisioning sites. We adapt and modify existing
      inference methods to reveal the underlying social structure of wide-ranging
      marine predators moving through spatial arrays of passive acoustic receivers.
      From six months of tracking data for grey reef sharks (Carcharhinus
      amblyrhynchos) at Palmyra atoll in the Pacific Ocean, we demonstrate that some
      individuals emerge as leaders within the population and that this behavioural
      coordination is predicted by both sex and the duration of co-occurrences between
      conspecifics. In doing so, we provide the first evidence of long-term, spatially
      extensive social processes in wild sharks. To achieve these results, we
      interrogate simulated and real tracking data with the explicit purpose of drawing
      attention to the key considerations in the use and interpretation of inference
      methods and their impact on resultant social structure. We provide a modified
      translation of the GMMEvents method for R, including new analyses quantifying the
      directionality and duration of social events with the aim of encouraging the
      careful use of these methods more widely in less tractable social animal systems
      but where passive telemetry is already widespread.

PMID- 27881804
TI  - Upgrading of automobile shredder residue via innovative granulation process
      'ReGran'.
AB  - Stricter regulatory requirements concerning end-of-life vehicles and rising
      disposal costs necessitate new ways for automobile shredder residue utilisation.
      The shredder granulate and fibres, produced by the VW-SICON-Process, have a high
      energy content of more than 20 MJ kg-1, which makes energy recovery an
      interesting possibility. Shredder fibres have a low bulk density of 60 kg m-3,
      which prevents efficient storing and utilisation as a refuse-derived fuel. By
      mixing fibres with plastic-rich shredder granulate and heating the mixture,
      defined granules can be produced. With this 'ReGran' process, the bulk density
      can be enhanced by a factor of seven by embedding shredder fibres in the
      partially melted plastic mass. A minimum of 26-33 wt% granulate is necessary to
      create enough melted plastic. The process temperature should be between 240 
      degrees C and 250  degrees C to assure fast melting while preventing extensive
      outgassing. A rotational frequency of the mixing tool of 1000 r min-1 during
      heating and mixing ensures a homogenous composition of the granules. During
      cooling, lower rotational frequencies generate bigger granules with particles
      sizes of up to 60 mm at 300 r min-1. To keep outgassing to a minimum, it is
      suggested to melt shredder granulate first and then add shredder fibres. Adding
      coal, wood or tyre fluff as a third component reduces chlorine levels to less
      than 1 wt%. The best results can be achieved with tyre fluff. In combination with
      the VW-SICON-Process, ReGran produces a solid recovered fuel or 'design fuel'
      tailored to the requirements of specific thermal processes.

PMID- 27881805
TI  - Corrosion resistance and biological activity of TiO2 implant coatings produced in
      oxygen-rich environments.
AB  - The physical and chemical properties of bio-titanium alloy implant surfaces play
      an important role in their corrosion resistance and biological activity. New
      turning and turning-rolling processes are presented, employing an oxygen-rich
      environment in order to obtain titanium dioxide layers that can both protect
      implants from corrosion and also promote cell adhesion. The surface topographies,
      surface roughnesses and chemical compositions of the sample surfaces were
      obtained using scanning electron microscopy, a white light interferometer, and
      the Auger electron spectroscopy, respectively. The corrosion resistance of the
      samples in a simulated body fluid was determined using electrochemical testing.
      Biological activity on the samples was also analyzed, using a vitro cell culture
      system. The results show that compared with titanium oxide layers formed using a
      turning process in air, the thickness of the titanium oxide layers formed using
      turning and turning-rolling processes in an oxygen-rich environment increased by
      4.6 and 7.3 times, respectively. Using an oxygen-rich atmosphere in the rolling
      process greatly improves the corrosion resistance of the resulting samples in a
      simulated body fluid. On samples produced using the turning-rolling process,
      cells spread quickly and exhibited the best adhesion characteristics.

PMID- 27881806
TI  - How do gloves affect cutaneous sensibility in medical practice? Two new applied
      tests.
AB  - In order to quantify the effect of medical gloves on tactile performance, two new
      Simulated Medical Examination Tactile Tests (SMETT) have been developed to
      replicate the tactile and haptic ability required in medical examinations: the
      'Bumps' test and the 'Princess and the Pea' (P&P) test. A pilot study was carried
      out using 30-40 subjects for each test in order to investigate the suitability of
      the tests for medical glove evaluation. Tests were performed with latex and
      nitrile examination gloves and without gloves. Following the tests, small-scale
      studies were carried out to investigate the effect of various design parameters,
      such as material stiffness and tactile exploration method. In the 'Bumps' test,
      subjects performed significantly better in the ungloved condition, and there were
      'almost significant' differences between the gloves, with the thinner latex
      gloves performing better than the thicker nitrile gloves. Both finger orientation
      and surface lubrication were found to have a significant effect on results,
      indicating that these need to be clearly defined in the test procedure. In the
      'P&P' test, no significant effect of hand condition was found, suggesting that
      haptic sensing is less affected by medical gloves than cutaneous sensibility.
      Other factors such as material stiffness, technique and test orientation had a
      more significant effect. The SMETT 'Bumps' test has potential as a clinical
      manual performance evaluation tool and may be used to evaluate the relative
      effects of different gloves. The SMETT 'P&P' test is a valid measure of haptic or
      tactile performance, but should not be used in glove evaluation. Both tests could
      have further applications, such as in the assessment of neurological impairment
      or aptitude testing for potential surgeons.

PMID- 27881807
TI  - Sarcopenia Is Highly Prevalent in Older Medical Patients With Mobility
      Limitation.
AB  - BACKGROUND: The association of sarcopenia with disability with ambulatory status
      is uncertain because most studies have targeted people who could walk
      independently. This study explored the prevalence of sarcopenia regardless of
      ambulatory status and the impact of ambulatory status on sarcopenia. MATERIALS
      AND METHODS: In total, 778 consecutive patients, aged >=65 years and admitted to
      a hospital, were enrolled. Ambulatory status was divided into 4 grades according
      to mobility as described in the Barthel index. Sarcopenia was defined as a loss
      of appendicular muscle mass index (AMI) with bioelectrical impedance and
      decreased muscle strength with handgrip strength (HGS); cutoff values were
      adopted from the Asian Working Group for Sarcopenia. RESULTS: The mean patient
      age was 83.2 +/- 8.3 years; 37.8% were male patients. Mobility limitation was
      associated with higher age, underweight body mass index, malnourishment, and
      comorbidities (all P < .001). AMI and HGS gradually decreased with declining
      ambulatory status ( P < .001). The prevalence of sarcopenia in the independent
      walk, walk with help, wheelchair, and immobile groups was 57.9%, 76.1%, 89.4%,
      and 91.7%, respectively. AMI prevalence declined and sarcopenia drastically
      increased in patients who were unable to walk independently compared with those
      who could walk independently ( P < .001). Multivariate regression analyses showed
      that mobility limitation was an independent indicator of decreasing AMI and
      sarcopenia after adjustment for confounders. CONCLUSION: Patients with dependent
      ambulatory status experienced a higher prevalence of sarcopenia compared with
      those with ambulation; in addition, decline in ambulatory status was an
      independent indicator for the presence of sarcopenia after adjustment for
      potential confounders.

PMID- 27881808
TI  - Jellyfish-Like Accessory Mitral Valve Tissue Causing Near-Collapse in a Young
      Child.
AB  - Accessory mitral valve tissue (AMVT) causing left ventricular outflow tract
      obstruction (LVOTO) is rare. We report a case of AMVT causing severe LVOTO
      resulting in acutely progressive symptoms of near-collapse. Urgent surgical
      resection eliminated the patient's life-threatening symptoms. AMVT should be
      considered among potential LVOTO diagnoses, and early surgical intervention may
      be required.

PMID- 27881809
TI  - Situs Inversus Totalis: Single-Stage Anatomic Repair of Complex Congenital Heart
      Disease.
AB  - Transposition of the great arteries occurs rarely in patients with mirror image
      dextrocardia and situs inversus, while the combination with severe coarctation of
      the descending aorta (CoA) makes the anatomy even more unusual. Therefore, it is
      not surprising that a case with such unusual and complicated anatomy presents
      unique problems when a primary definitive correction is attempted. We report a
      patient with situs inversus totalis and complex congenital heart disease
      including transposition of the great arteries and severe CoA who underwent
      successful complete, single-stage, anatomic correction.

PMID- 27881810
TI  - An Unusual Case of Raghib Defect and Double-Orifice Tricuspid Valve.
AB  - Raghib defect and double-orifice tricuspid valve are two rare congenital heart
      defects. We report a case of a 42-year-old man with both Raghib defect and DOTV.
      The patient underwent reroofing of the coronary sinus with an intra-atrial baffle
      and annuloplasty of the tricuspid and mitral valves via median sternotomy.

PMID- 27881811
TI  - Perceived Social Support and Physical Activity Among Patients With Coronary
      Artery Disease.
AB  - Adherence to recommended physical activity after a cardiac event is important to
      prevent cardiac recurrence. Social support from peers and family is known to
      improve self-care in chronic illnesses, including cardiovascular disease.
      However, the relationship between social support from health care providers and
      physical activity among patients with coronary artery disease remains unclear.
      This cross-sectional study aimed to identify the relationship between perceived
      social support from health care providers and physical activity among patients
      with stable coronary artery disease. The study included 237 patients with stable
      coronary artery disease attending an outpatient clinic. Hierarchical linear
      regression found that perceived social support explained 12% of variance in
      physical activity, F(14, 222) = 7.37, p < .001. In addition, self-efficacy
      partially mediated the relationships between perceived social support and
      physical activity. Abundant support from health care providers plays a key role
      in promoting physical activity among patients with stable coronary artery
      disease.

PMID- 27881812
TI  - Pruritic nodular secondary syphilis in a 61-year-old man with HIV infection.
AB  - The typical finding in secondary syphilis stage is a generalized non-pruritic
      maculopapular eruption. We report a case of secondary syphilis in an HIV-infected
      patient presenting with pruritic crusted nodules showing numerous eosinophils on
      the histopathological examination.

PMID- 27881813
TI  - Perspectives of US and Australian Hand Therapists About Pediatric Hand
      Transplantation.
AB  - INTRODUCTION: Pediatric hand transplantation (PHT), an investigational therapy,
      was recently performed in the United States. RESEARCH QUESTIONS: Perspectives of
      hand therapists about PHT patient selection (inclusion and exclusion criteria),
      team configuration, patient assent, and patient compliance were explored. DESIGN:
      Quantitative survey. We used a research ethics committee-approved 18-question e
      link anonymous questionnaire to survey members of the American Society of Hand
      Therapists and the Australian (AU) Hand Therapy Association for their
      perspectives on PHT. RESULTS: All surveyed hand therapists work with children (n
      = 18 Australia [AU], n = 85 United States) and some had been involved in adult
      hand transplant rehabilitation (28% AU, 21% United States; P = .543, not
      significant (NS)). The US and AU therapists differ regarding their opinions on
      multidisciplinary team membership, smoking as an exclusion criterion, and risk of
      posttransplant rehabilitation noncompliance. DISCUSSION: This research opens a
      dialogue on the clinical and ethical complexity of PHT, including team
      configuration, inclusion/exclusion criteria, the assent process, and
      rehabilitation access/compliance. Furthermore, international perspectives are
      informative as they highlight funding and access issues and can potentially guide
      global professional society policy.

PMID- 27881814
TI  - Chronic Norovirus Infections in Cardiac Transplant Patients.
AB  - Norovirus is a common self-limiting gastrointestinal infection, but in transplant
      recipients, symptoms can last for months and result in serious health
      complications. As there is currently no established treatment for chronic
      norovirus infection in transplant patients, management has been directed at
      symptom control, trial of various antivirals, and ultimately reductions in
      immunosuppression. We present 3 cases of chronic norovirus infection in cardiac
      transplant patients to illustrate various approaches to diagnosis, the prolonged
      nature of disease symptoms, and treatment options. When managing a transplant
      recipient with chronic diarrhea, considering a broad differential as well as
      maintaining a high suspicion for infectious etiologies is key. A stepwise
      approach to management includes termination of diarrhea-causing medications,
      trials of nitazoxanide and immunoglobulin, and reductions in immunosuppressive
      therapies. Although brief discontinuation of immunosuppression is often required
      to achieve symptom, graft rejection is often a complication.

PMID- 27881815
TI  - Investigation of Eligible Picture Categories for Use as Environmental Cues in
      Dementia-Sensitive Environments.
AB  - OBJECTIVES: Environmental cues, such as pictures, could be helpful in improving
      room-finding and wayfinding abilities among older patients. The aim of this study
      was to identify picture categories that are preferred and easily remembered by
      older patients and cognitively impaired patients and which therefore might be
      suitable for use as environmental cues in acute care settings. METHODS: Twelve
      pictures were presented to a sample of older patients ( n = 37). The pictures
      represented different categories: familiarity (familiar vs. unfamiliar), type of
      shot (close-up vs. wide shot), and picture content (nature vs. animal vs. urban).
      We tested the patients' votes of preference and abilities to identify and
      immediately recall pictures. Cognitively impaired patients ( n = 14) were
      assessed by the abbreviated mental test and the mini mental state examination and
      were compared with patients without cognitive impairments ( n = 23) using a
      repeated measures analysis of variance. RESULTS: The results showed a main effect
      of familiarity on positive vote and recall of pictures. The absence of
      interaction effects of familiarity and group indicated an overall impact of
      familiarity on the sample. Within cognitively impaired patients, a significant
      difference in recall of picture content between urban (20%) and animal (9%) was
      found. CONCLUSIONS: Pictures, which patients were able to relate to in terms of
      familiarity and the characteristics urban and nature, seem to be suitable for use
      as environmental cues. Besides functioning as such, we assume, based on
      literature, that pictures could further enhance the ambiance or serve as prompts
      for communication and interaction.

PMID- 27881817
TI  - Photoacoustic imaging sounds the alarm on liver fibrosis.

PMID- 27881816
TI  - Hypothermia-treated neonates with hypoxic-ischemic encephalopathy: Optimal timing
      of quantitative ADC measurement to predict disease severity.
AB  - To determine the optimal time window for MR imaging with quantitative ADC
      measurement in neonatal HIE after hypothermia treatment, a retrospective review
      was performed on consecutive hypothermia-treated term neonates with HIE, with an
      initial and follow-up MR imaging within the first two weeks of life. Three
      neuroradiologists categorized each set of MR imaging as normal, mild, moderate or
      severe HIE based on a consensus review of the serial imaging. The lowest ADC
      values from the white matter, corpus callosum, and basal ganglia/thalamus were
      measured. The ADC values between mild-moderate and severe HIE were compared using
      a Student's t-test over a range of different time windows. A total of 33 MR
      imaging examinations were performed on 16 neonates that included three normal,
      four mild, five moderate, and four severe HIE. The time window of 3-10 days
      showed a statistically significant decrease in ADC value in severe HIE compared
      to mild-moderate HIE in all three locations, respectively: white matter 0.5 +/-
      0.22 versus 0.83 +/- 0.27 ( p value 0.01), corpus callosum 0.69 +/- 0.19 versus
      0.91 +/- 0.17 ( p value 0.01), and basal ganglia/thalamus 0.63 +/- 0.16 versus
      0.98 +/- 0.06 ( p value <0.01). The range of 3-10 days is the optimal time window
      for MR imaging with quantitative ADC after hypothermia treatment.

PMID- 27881818
TI  - Bugs clogging your arteries? Take an anti-B2 shot.

PMID- 27881819
TI  - Sweet signals and diabetes: Carbohydrate-binding proteins contribute to insulin
      resistance.

PMID- 27881820
TI  - Biomaterials-based biologic burst release builds better bone.

PMID- 27881821
TI  - NIH's transformative opportunities for the behavioral and social sciences.

PMID- 27881823
TI  - Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation.
AB  - Ion channels are desirable therapeutic targets, yet ion channel-directed drugs
      with high selectivity and few side effects are still needed. Unlike small
      molecule inhibitors, antibodies are highly selective for target antigens but
      mostly fail to antagonize ion channel functions. Nanobodies-small, single-domain
      antibody fragments-may overcome these problems. P2X7 is a ligand-gated ion
      channel that, upon sensing adenosine 5'-triphosphate released by damaged cells,
      initiates a proinflammatory signaling cascade, including release of cytokines,
      such as interleukin-1beta (IL-1beta). To further explore its function, we
      generated and characterized nanobodies against mouse P2X7 that effectively
      blocked (13A7) or potentiated (14D5) gating of the channel. Systemic injection of
      nanobody 13A7 in mice blocked P2X7 on T cells and macrophages in vivo and
      ameliorated experimental glomerulonephritis and allergic contact dermatitis. We
      also generated nanobody Dano1, which specifically inhibited human P2X7. In
      endotoxin-treated human blood, Dano1 was 1000 times more potent in preventing IL
      1beta release than small-molecule P2X7 antagonists currently in clinical
      development. Our results show that nanobody technology can generate potent,
      specific therapeutics against ion channels, confirm P2X7 as a therapeutic target
      for inflammatory disorders, and characterize a potent new drug candidate that
      targets P2X7.

PMID- 27881822
TI  - Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric
      posterior fossa ependymomas.
AB  - Childhood posterior fossa (PF) ependymomas cause substantial morbidity and
      mortality. These tumors lack recurrent genetic mutations, but a subset of these
      ependymomas exhibits CpG island (CpGi) hypermethylation [PF group A (PFA)],
      implicating epigenetic alterations in their pathogenesis. Further, histological
      grade does not reliably predict prognosis, highlighting the importance of
      developing more robust prognostic markers. We discovered global H3K27me3
      reduction in a subset of these tumors (PF-ve ependymomas) analogous to H3K27M
      mutant gliomas. PF-ve tumors exhibited many clinical and biological similarities
      with PFA ependymomas. Genomic H3K27me3 distribution showed an inverse
      relationship with CpGi methylation, suggesting that CpGi hypermethylation drives
      low H3K27me3 in PF-ve ependymomas. Despite CpGi hypermethylation and global
      H3K27me3 reduction, these tumors showed DNA hypomethylation in the rest of the
      genome and exhibited increased H3K27me3 genomic enrichment at limited genomic
      loci similar to H3K27M mutant gliomas. Combined integrative analysis of PF-ve
      ependymomas with H3K27M gliomas uncovered common epigenetic deregulation of
      select factors that control radial glial biology, and PF radial glia in early
      human development exhibited reduced H3K27me3. Finally, H3K27me3 immunostaining
      served as a biomarker of poor prognosis and delineated radiologically invasive
      tumors, suggesting that reduced H3K27me3 may be a prognostic indicator in PF
      ependymomas.

PMID- 27881824
TI  - Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic
      ossification.
AB  - Fibrodysplasia ossificans progressiva (FOP), a congenital heterotopic
      ossification (HO) syndrome caused by gain-of-function mutations of bone
      morphogenetic protein (BMP) type I receptor ACVR1, manifests with progressive
      ossification of skeletal muscles, tendons, ligaments, and joints. In this
      disease, HO can occur in discrete flares, often triggered by injury or
      inflammation, or may progress incrementally without identified triggers. Mice
      harboring an Acvr1R206H knock-in allele recapitulate the phenotypic spectrum of
      FOP, including injury-responsive intramuscular HO and spontaneous articular,
      tendon, and ligament ossification. The cells that drive HO in these diverse
      tissues can be compartmentalized into two lineages: an Scx+ tendon-derived
      progenitor that mediates endochondral HO of ligaments and joints without
      exogenous injury, and a muscle-resident interstitial Mx1+ population that
      mediates intramuscular, injury-dependent endochondral HO. Expression of
      Acvr1R206H in either lineage confers aberrant gain of BMP signaling and
      chondrogenic differentiation in response to activin A and gives rise to mutation
      expressing hypertrophic chondrocytes in HO lesions. Compared to Acvr1R206H,
      expression of the man-made, ligand-independent ACVR1Q207D mutation accelerates
      and increases the penetrance of all observed phenotypes, but does not abrogate
      the need for antecedent injury in muscle HO, demonstrating the need for an injury
      factor in addition to enhanced BMP signaling. Both injury-dependent intramuscular
      and spontaneous ligament HO in Acvr1R206H knock-in mice were effectively
      controlled by the selective ACVR1 inhibitor LDN-212854. Thus, diverse phenotypes
      of HO found in FOP are rooted in cell-autonomous effects of dysregulated ACVR1
      signaling in nonoverlapping tissue-resident progenitor pools that may be
      addressed by systemic therapy or by modulating injury-mediated factors involved
      in their local recruitment.

PMID- 27881827
TI  - Limitations in interpreting assessment of depression in patients with advanced
      cancer.

PMID- 27881825
TI  - Effects of a gut pathobiont in a gnotobiotic mouse model of childhood
      undernutrition.
AB  - To model how interactions among enteropathogens and gut microbial community
      members contribute to undernutrition, we colonized gnotobiotic mice fed
      representative Bangladeshi diets with sequenced bacterial strains cultured from
      the fecal microbiota of two 24-month-old Bangladeshi children: one healthy and
      the other underweight. The undernourished donor's bacterial collection contained
      an enterotoxigenic Bacteroides fragilis strain (ETBF), whereas the healthy
      donor's bacterial collection contained two nontoxigenic strains of B. fragilis
      (NTBF). Analyses of mice harboring either the unmanipulated culture collections
      or systematically manipulated versions revealed that ETBF was causally related to
      weight loss in the context of its native community but not when introduced into
      the healthy donor's community. This phenotype was transmissible from the dams to
      their offspring and was associated with derangements in host energy metabolism
      manifested by impaired tricarboxylic acid cycle activity and decreased acyl
      coenzyme A utilization. NTBF reduced ETBF's expression of its enterotoxin and
      mitigated the effects of ETBF on the transcriptomes of other healthy donor
      community members. These results illustrate how intraspecific (ETBF-NTBF) and
      interspecific interactions influence the effects of harboring B. fragilis.

PMID- 27881826
TI  - A soft, wearable microfluidic device for the capture, storage, and colorimetric
      sensing of sweat.
AB  - Capabilities in health monitoring enabled by capture and quantitative chemical
      analysis of sweat could complement, or potentially obviate the need for,
      approaches based on sporadic assessment of blood samples. Established sweat
      monitoring technologies use simple fabric swatches and are limited to basic
      analysis in controlled laboratory or hospital settings. We present a collection
      of materials and device designs for soft, flexible, and stretchable microfluidic
      systems, including embodiments that integrate wireless communication electronics,
      which can intimately and robustly bond to the surface of the skin without
      chemical and mechanical irritation. This integration defines access points for a
      small set of sweat glands such that perspiration spontaneously initiates routing
      of sweat through a microfluidic network and set of reservoirs. Embedded chemical
      analyses respond in colorimetric fashion to markers such as chloride and
      hydronium ions, glucose, and lactate. Wireless interfaces to digital image
      capture hardware serve as a means for quantitation. Human studies demonstrated
      the functionality of this microfluidic device during fitness cycling in a
      controlled environment and during long-distance bicycle racing in arid, outdoor
      conditions. The results include quantitative values for sweat rate, total sweat
      loss, pH, and concentration of chloride and lactate.

PMID- 27881828
TI  - "Hope for the best, prepare for the worst": A qualitative interview study on
      parents' needs and fears in pediatric advance care planning.
AB  - BACKGROUND: Pediatric advance care planning is advocated by healthcare providers
      because it may increase the chance that patient and/or parent wishes are
      respected and thus improve end-of-life care. However, since end-of-life decisions
      for children are particularly difficult and charged with emotions, physicians are
      often afraid of addressing pediatric advance care planning. AIM: We aimed to
      investigate parents' views and needs regarding pediatric advance care planning.
      DESIGN: We performed a qualitative interview study with parents of children who
      had died from a severe illness. The interviews were analyzed by descriptive and
      evaluation coding according to Saldana. SETTING/PARTICIPANTS: We conducted semi
      structured interviews with 11 parents of 9 children. Maximum variation was sought
      regarding the child's illness, age at death, care setting, and parent gender.
      RESULTS: Parents find it difficult to engage in pediatric advance care planning
      but consider it important. They argue for a sensitive, individualized, and
      gradual approach. Hope and quality of life issues are primary. Parents have many
      non-medical concerns that they want to discuss. Written advance directives are
      considered less important, but medical emergency plans are viewed as necessary in
      particular cases. Continuity of care and information should be improved through
      regular pediatric advance care planning meetings with the various care providers.
      Parents emphasize the importance of a continuous contact person to facilitate
      pediatric advance care planning. CONCLUSION: Despite a need for pediatric advance
      care planning, it is perceived as challenging. Needs-adjusted content and process
      and continuity of communication should be a main focus in pediatric advance care
      planning. Future research should focus on strategies that facilitate parent
      engagement in pediatric advance care planning to increase the benefit for the
      families.

PMID- 27881829
TI  - Biomechanical Comparison of Fixation Devices for First Metatarsocuneiform Joint
      Arthrodesis.
AB  - : Common surgical treatment of first tarsal-metatarsal arthritis is by first
      metatarsocuneiform joint arthrodesis. While crossed-screw and locking plate
      fixation are the most widely used methods, a novel construct was designed to
      alleviate soft tissue irritation while still providing stable fixation. Using
      anatomic first metatarsal and medial cuneiform composites, we compared 3
      arthrodesis implants (crossed-screw, dorsal locking plate, and IO Fix) under 2
      cyclic bending loading scenarios (cantilever and 4-point bending). Additionally,
      the optimal orientation (plantar-dorsal or dorsal-plantar) of the IO Fix
      construct was determined. Failure load, diastasis, joint space angle, and axial
      and angular stiffness were determined. Both crossed-screw fixation and the IO Fix
      constructs experienced significantly higher failure loads than the dorsal locking
      plate during both loading scenarios. Additionally, they had lower plantar
      diastasis and joint space angle at failure than the plate. Moreover, the plantar
      dorsal IO Fix construct was significantly stiffer than the crossed-screw during
      cantilever bending. Finally, the plantar-dorsal orientation of the IO Fix device
      had higher failure load and lower diastasis and angle at failure than in the
      dorsal-plantar orientation. The results suggest that the IO Fix system can reduce
      motion at the interfragmentary site and ensure compression for healing comparable
      to that of the crossed-screw fixation. LEVELS OF EVIDENCE: Level V: Bench
      testing.

PMID- 27881830
TI  - Repair of Chronic Achilles Ruptures Has a High Incidence of Venous
      Thromboembolism.
AB  - BACKGROUND: Despite the low incidence of deep vein thrombosis (DVT) in foot and
      ankle surgery, some authors report a high incidence of symptomatic DVT following
      Achilles tendon rupture. The purpose of this study was to identify DVT risk
      factors inherent to Achilles tendon repair to determine which patients may
      benefit from prophylaxis. METHODS: One hundred and thirteen patient charts were
      reviewed following elective and nonelective Achilles tendon repair. For elective
      repair of insertional or noninsertional Achilles tendinopathy, parameters
      examined included lateral versus prone positioning and the presence versus
      absence of a flexor hallucis longus transfer. For nonelective repair, acute
      Achilles tendon ruptures were compared to chronic Achilles tendon ruptures.
      RESULTS: Of 113 Achilles tendon repairs, 3 venous thromboembolism (VTE) events
      (2.65%) occurred including 2 pulmonary emboli (1.77%). Seventeen of these repairs
      were chronic Achilles tendon ruptures, and all 3 VTE events (17.6%) occurred
      within this subgroup. Elevated body mass index was associated with VTE in
      patients with chronic Achilles ruptures although this did not reach significance
      ( P = .064). No VTE events were reported after repair of 28 acute tendon ruptures
      or after 68 elective repairs of tendinopathy. Two patients with misdiagnosed
      partial Achilles tendon tears were excluded because they experienced a VTE event
      3 weeks and 5 weeks after injury, prior to surgery. CONCLUSION: In our
      retrospective review, chronic Achilles ruptures had a statistically significant
      higher incidence of VTE compared with acute Achilles ruptures ( P = .048) or
      elective repair ( P = .0069). Pharmaceutical anticoagulation may be considered
      for repair of chronic ruptures. Repair of acute ruptures and elective repair may
      not warrant routine prophylaxis due to a lower incidence of VTE. LEVELS OF
      EVIDENCE: Prognostic, Level III: Case Control Study.

PMID- 27881831
TI  - The Effect of Suture Anchor Insertion Angle on Calcaneus Pullout Strength:
      Challenging the Deadman's Angle.
AB  - BACKGROUND: Refractory cases of Achilles tendinopathy amenable to surgery may
      include reattachment of the tendon using suture anchors. However, there is
      paucity of information describing the optimal insertion angle to maximize the
      tendon footprint and anchor stability in the calcaneus. The purpose of this
      investigation is to compare the fixation strength of suture anchors inserted at
      90 degrees  and 45 degrees  (the Deadman's angle) relative to the primary
      compressive trabeculae of the calcaneus. METHODS: A total of 12 matched pairs of
      adult cadaveric calcanei were excised and potted to approximate their alignment
      in vivo. Each pair was implanted with 5.5-mm bioabsorbable suture anchors placed
      either perpendicular (90 degrees ) or oblique (45 degrees ) to the primary
      compressive trabeculae. A tensile load was applied until failure of anchor
      fixation. Differences in failure load and stiffness between anchor fixation
      angles were determined by paired t-tests. RESULTS: No significant differences
      were detected between perpendicular and oblique suture anchor insertion relative
      to primary compressive trabeculae in terms of load to failure or stiffness.
      CONCLUSION: This investigation suggests that the fixation strength of suture
      anchors inserted perpendicular to the primary compression trabeculae and at the
      Deadman's angle are possibly comparable. LEVELS OF EVIDENCE: Biomechanical
      comparison study.

PMID- 27881832
TI  - Hematogenous Calcaneal Osteomyelitis in Children.
AB  - : Osteomyelitis in children commonly affects long bones such as the femur, tibia,
      and humerus. There have been relatively few documented studies of osteomyelitis
      at unusual locations, such as the calcaneus. The objective of this study is to
      systematically review information on the diagnostic and treatment methods of
      calcaneal osteomyelitis as well as associated complications. Methods included
      research database searches using primarily PubMed and EMBASE databases. Results
      of the review show no clear approach to diagnosis and treatment of calcaneal
      osteomyelitis in children. Clinical presentation of refusal to bear weight was
      the most common clinical symptom. Magnetic resonance imaging was 100% diagnostic
      in studies that used this modality, compared with X-rays, which were 14%-71.4%
      diagnostic. Blood cultures were diagnostic in 27% to 55% of cases, and
      erythrocyte sedimentation rate was elevated in 79% to 97% of cases. Methicillin
      sensitive Staphylococcus aureus was the most common cultured organism. Treatment
      involved either antibiotics alone or in combination with surgical
      debridement/evacuation. Penicillin, penicillin derivatives, cephalosporins,
      clindamycin, and chloramphenicol were the most commonly used antibiotics, with
      duration varying from 5 days to 10 weeks. The most common complication was
      recurrent osteomyelitis. LEVELS OF EVIDENCE: III.

PMID- 27881834
TI  - An unusual case of repeated splenectomy: traumatic rupture of an accessory spleen
      in a previously splenectomized patient.
AB  - : The traumatic rupture of an accessory spleen is a very rare condition and only
      few cases have been reported in the literature. We describe the case of a 51-year
      old man undergone splenectomy for trauma several years before, who developed
      hemoperitoneum due to a laceration of a voluminous accessory spleen, following an
      accidental two-meter fall. As a conservative management of the injury was not
      possible, an accessory splenectomy was then required. Thus, a briefly review of
      the literature about this uncommon topic was perfomed. KEY WORDS: Accessory
      spleen, Laparotomy, Trauma.

PMID- 27881833
TI  - Apixaban for treatment of embolic stroke of undetermined source (ATTICUS
      randomized trial): Rationale and study design.
AB  - Rationale Optimal secondary prevention of embolic stroke of undetermined source
      is not established. The current standard in these patients is acetylsalicylic
      acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation.
      Aim The ATTICUS randomized trial is designed to determine whether the factor Xa
      inhibitor apixaban administered within 7 days after embolic stroke of
      undetermined source, is superior to acetylsalicylic acid for prevention of new
      ischemic lesions documented by brain magnetic resonance imaging within 12 months
      after index stroke. Design Prospective, randomized, blinded, parallel-group, open
      label, German multicenter phase III trial in approximately 500 patients with
      embolic stroke of undetermined source. A key inclusion criterion is the presence
      or the planned implantation of an insertable cardiac monitor. Patients are 1:1
      randomized to apixaban or acetylsalicylic acid and treated for a 12-month period.
      It is an event-driven trial aiming for core-lab adjudicated primary outcome
      events. Study outcomes The primary outcome is the occurrence of at least one new
      ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging
      and/or axial DWI magnetic resonance imaging at 12 months when compared with the
      baseline magnetic resonance imaging. Key secondary outcomes are the combination
      of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism;
      combination of MACE including recurrent stroke, myocardial infarction, and
      cardiovascular death and combination of major and clinically relevant non-major
      bleeding defined according to ISTH, and change of cognitive function and quality
      of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined
      source is caused by embolic disease and associated with a high risk of recurrent
      ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will
      investigate the impact of atrial fibrillation detected by insertable cardiac
      monitor and the effects of early anticoagulation with apixaban compared with
      antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic
      lesion after embolic stroke of undetermined source.

PMID- 27881835
TI  - Leptospirosis-Associated Severe Pulmonary Hemorrhagic Syndrome with Lower Back
      Pain as an Initial Symptom.
AB  - BACKGROUND Leptospirosis is a zoonosis transmitted through urine of infected
      animals. Symptoms range from mild influenza-like symptoms to severe pulmonary
      hemorrhagic syndrome (SPHS); the latter are often fatal. The serogroup
      distribution in Denmark has changed from 1988 to 2012, with Icterohaemorrhagiae
      and Sejroe now being predominant. CASE REPORT A 45-year-old Danish woman living
      in an area endemic for Hanta virus, without prior medical history, was admitted
      because of lower back pain radiating to the left hip, fever, headache, nausea,
      and malaise. Two weeks before admission she had been bitten by a mouse or a rat.
      Blood tests revealed raised white cells and CRP, electrolyte imbalances, raised
      creatinine, low thrombocytes, and a slightly decreased clotting factor (II, VII,
      and X). Treatment with broad-spectrum intravenous antibiotics and supporting
      therapy was initiated very quickly. Eight hours after admission she died from
      respiratory failure where severe hemoptysis was observed. Leptospiral DNA was
      later detected in a urine sample. CONCLUSIONS This case represents leptospirosis
      with severe pulmonary hemorrhagic syndrome. In spite of immediate treatment with
      broad-spectrum antibiotics, the patient died a few hours after hospital
      admission.

PMID- 27881836
TI  - Relationship Between Lesions in Adenomatous Polyp-Dysplasia-Colorectal Cancer
      Sequence and Neutrophil-to-Lymphocyte Ratio.
AB  - BACKGROUND The aim of our study was to evaluate all lesions in the adenoma
      dysplasia-cancer sequence of the colon and to examine whether the neutrophil-to
      lymphocyte ratio (NLR) can distinguish polyps indicating dysplasia and cancer.
      MATERIAL AND METHODS A total of 397 patients who had colonoscopic polypectomy
      between January 2010 and December 2014 were included in our retrospective study.
      The patients were divided into four groups: patients with hyperplastic polyps,
      patients with adenomatous polyps, patients with dysplasia, and patients with
      cancer. The NLR was calculated as a simple ratio indicating the relationship
      between counts of absolute neutrophil and absolute lymphocyte. RESULTS The NLR
      increased in line with the adenomatous polyp-dysplasia-cancer sequence, with the
      highest ratio established among cancer patients (2.05 (0.27-10), 2.34 (0.83
      14.70) and 3.25 (0.81-10.0), respectively). The NLR was significantly higher
      among cancer patients than among patients with adenomatous polyps and
      hyperplastic polyps (p values were 0.001 and 0.004, respectively). The lymphocyte
      count of cancer patients was prominently lower when compared to those in groups
      with adenomatous polyps and hyperplastic polyps (p values were 0.001 and 0.003,
      respectively). The NLR was found to be significantly higher in patients with
      polyps larger than 10 mm [2.71 (0.90-14.70)] when compared to those with polyps
      smaller than 10 mm [2.28 (0.27-11.67)] (p<0.001). With the NLR threshold set at
      2.20, it was possible to predict cancerous polyps with a sensitivity of 71.4% and
      a specificity of 52.5% (AUC: 0.665, 95% CI: 0.559-0.772, p=0.001). CONCLUSIONS
      NLR is a cheap, universally available, simple and reliable test that can help
      predict cancerous polyps. It can be used as a non-invasive test for monitoring
      polyps.

PMID- 27881837
TI  - Systemic and mucosal immune responses following oral adenoviral delivery of
      influenza vaccine to the human intestine by radio controlled capsule.
AB  - There are several benefits of oral immunization including the ability to elicit
      mucosal immune responses that may protect against pathogens that invade through a
      mucosal surface. Our understanding of human immune biology is hampered by the
      difficulty in isolating mucosal cells from humans, and the fact that animal
      models may or may not completely mirror human intestinal immunobiology. In this
      human pharmacodynamic study, a novel adenovirus vector-based platform expressing
      influenza hemagglutinin was explored. We used radio-controlled capsules to
      deliver the vaccine to either the jejunum or the ileum. The resulting immune
      responses induced by immunization at each of the intestinal sites were
      investigated. Both intestinal sites were capable of inducing mucosal and systemic
      immune responses to influenza hemagglutinin, but ileum delivery induced higher
      numbers of antibody secreting cells of IgG and IgA isotypes, increased mucosal
      homing B cells, and higher number of vaccine responders. Overall, these data
      provided substantial insights into human mucosal inductive sites, and aided in
      the design and selection of indications that could be used with this oral vaccine
      platform.

PMID- 27881838
TI  - Fabrication of Ion-Shaped Anisotropic Nanoparticles and their Orientational
      Imaging by Second-Harmonic Generation Microscopy.
AB  - Ion beam shaping is a novel and powerful tool to engineer nanocomposites with
      effective three-dimensional (3D) architectures. In particular, this technique
      offers the possibility to precisely control the size, shape and 3D orientation of
      metallic nanoparticles at the nanometer scale while keeping the particle volume
      constant. Here, we use swift heavy ions of xenon for irradiation in order to
      successfully fabricate nanocomposites consisting of anisotropic gold nanoparticle
      that are oriented in 3D and embedded in silica matrix. Furthermore, we
      investigate individual nanorods using a nonlinear optical microscope based on
      second-harmonic generation (SHG). A tightly focused linearly or radially
      polarized laser beam is used to excite nanorods with different orientations. We
      demonstrate high sensitivity of the SHG response for these polarizations to the
      orientation of the nanorods. The SHG measurements are in excellent agreement with
      the results of numerical modeling based on the boundary element method.

PMID- 27881840
TI  - A combined linkage and association strategy identifies a variant near the GSTP1
      gene associated with BMI in the Mexican population.
AB  - Obesity is a major public health concern in Mexico and worldwide. Although the
      estimated heritability is high, common variants identified by genome-wide
      association studies explain only a small proportion of this heritability. A
      combination of linkage and association strategies could be a more robust and
      powerful approach to identify other obesity-susceptibility variants. We thus
      sought to identify novel genetic variants associated with obesity-related traits
      in the Mexican population by combining these methods. We performed a genome-wide
      linkage scan for body mass index (BMI) and other obesity-related phenotypes in 16
      Mexican families using the Sequential Oligogenic Linkage Analysis Routines
      Program. Associated single-nucleotide polymorphisms (SNPs) were tested for
      associations in an independent cohort. Two suggestive BMI-linkage peaks
      (logarithm of odds ?1.5) were observed at chromosomal regions 11q13 and 13q22.
      Only rs614080 in the 11q13 region was significantly associated with BMI and
      related traits in these families. This association was also significant in an
      independent cohort of Mexican adults. Moreover, this variant was significantly
      associated with GSTP1 gene expression levels in adipose tissue. In conclusion,
      the rs614080 SNP near the GSTP1 gene was significantly associated with BMI and
      GSTP1 expression levels in the Mexican population.

PMID- 27881839
TI  - A polymorphism in human MR1 is associated with mRNA expression and susceptibility
      to tuberculosis.
AB  - The MR1 antigen-presenting system is conserved among mammals and enables T cells
      to recognize small molecules produced by bacterial pathogens, including
      Mycobacterium tuberculosis (M.tb). However, it is not known whether MR1-mediated
      antigen presentation is important for protective immunity against mycobacterial
      disease. We hypothesized that genetic control of MR1 expression correlates with
      clinical outcomes of tuberculosis infection. We performed an MR1 candidate gene
      association study and identified an intronic single-nucleotide polymorphism
      (rs1052632) that was significantly associated with susceptibility to tuberculosis
      in a discovery and validation cohort of Vietnamese adults with tuberculosis.
      Stratification by site of disease revealed that rs1052632 genotype GG was
      strongly associated with the development of meningeal tuberculosis (odds
      ratio=2.99; 95% confidence interval (CI) 1.64-5.43; P=0.00006). Among patients
      with meningeal disease, absence of the G allele was associated with an increased
      risk of death (hazard ratio=3.86; 95% CI 1.49-9.98; P=0.005). Variant annotation
      tools using public databases indicate that rs1052632 is strongly associated with
      MR1 gene expression in lymphoblastoid cells (P=0.004) and is located within a
      transcriptional enhancer in epithelial keratinocytes. These data support a role
      for MR1 in the pathogenesis of human tuberculosis by revealing that rs1052632 is
      associated with MR1 gene expression and susceptibility to tuberculosis in
      Vietnam.

PMID- 27881841
TI  - Novel and recurrent XYLT1 mutations in two Turkish families with Desbuquois
      dysplasia, type 2.
AB  - Desbuquois dysplasia (DBQD) is an autosomal recessive skeletal disorder
      characterized by growth retardation, joint laxity, short extremities, and
      progressive scoliosis. DBQD is classified into two types based on the presence
      (DBQD1) or absence (DBQD2) of characteristic hand abnormalities. CANT1 mutations
      have been reported in both DBQD1 and DBQD2. Recently, mutations in the gene
      encoding xylosyltransferase 1 (XYLT1) were identified in several families with
      DBQD2. In this study, we performed whole-exome sequencing in two Turkish families
      with DBQD2. We found a novel and a recurrent XYLT1 mutation in each family. The
      patients were homozygous for the mutations. Our results further support that
      XYLT1 is responsible for a major subset of DBQD2.

PMID- 27881842
TI  - The investigation of the origin of Southern Tunisians using HLA genes.
AB  - The south of Tunisia is characterized by marked ethnic diversity, highlighted by
      the coexistence of native Berbers with Blacks, Jews and Arab-speaking
      populations. Despite this heterogeneity, genetic anthropology studies
      investigating the origin of current Southern Tunisians were rarely reported. We
      examined human leukocyte antigen (HLA) class I (A, B) and class II (DRB1, DQB1)
      gene profiles of 250 unrelated Southern Tunisians, and compared them with those
      of Arab-speaking communities, along with Mediterranean and sub-Sahara African
      populations using genetic distances, neighbor-joining dendrograms, correspondence
      and haplotype analysis. In total, 137 HLA alleles were detected, which comprised
      32 HLA-A, 52 HLA-B, 32 DRB1 and 21 DQB1 alleles. The most frequent alleles were
      HLA-A*02:01(18.02%), HLA-B*50:01 (9.11%), HLA-DRB1*07:01 (22.06%) and HLA
      DQB1*02:01 (17.21%). All pairs of HLA loci show significant linkage
      disequilibrium. The four loci depict negative Fnd (the normalized deviate of the
      homozygosity) values indicating an overall trend to balancing selection. Southern
      Tunisians appear to be closely related to others Tunisian populations including
      Berbers, North Africans and Iberians. On the contrary, Southern Tunisians were
      distinct from Palestinian, Lebanese and Jordanian Middle Eastern Arab-speaking
      population, despite the deep Arab incursions and Arabization that affected
      Southern Tunisia. In addition, Southern Tunisians were distant from many sub
      Saharan communities, evidenced by genetic distance analysis. Collectively, this
      indicates a limited genetic contribution of Arab invasion and Black caravans on
      the makeup of Southern Tunisian gene pool.

PMID- 27881843
TI  - Comparison of exome-based HLA class I genotyping tools: identification of
      platform-specific genotyping errors.
AB  - Accurate human leukocyte antigen (HLA) genotyping is critical in studies
      involving the immune system. Several algorithms to estimate HLA genotypes from
      whole-exome data were developed. We compared the accuracy of seven algorithms,
      including Optitype, Polysolver and PHLAT, as well as investigated patterns and
      possible causes of miscalls using 12 clinical samples and 961 individuals from
      the 1000 Genomes Project. Optitype showed the highest accuracy of 97.2% for HLA
      class I alleles at the second field resolution, followed by 94.0% in Polysolver
      and 85.6% in PHLAT. In Optitype, 34 (21.1%) of 161 miscalls were across different
      serological types, and common miscalls were HLA-A*26:01 to HLA-A*25:01, HLA
      B*45:01 to HLA-B*44:15 and HLA-C*08:02 to HLA-C*05:01 with error rates of 4.1%,
      10.0% and 4.1%, respectively. In Polysolver, 193 (55.9%) of 345 miscalls occurred
      across different serological alleles, and a specific pattern of genotyping error
      from HLA-A*25:01 to HLA-A*26:01 was observed in 93.3% of HLA-A*25:01 carriers,
      due to dropping of HLA-A*25:01 sequence reads during the extraction process of
      HLA reads. In PHLAT, 147 (59.8%) of 246 miscalls in HLA-A were due to erroneous
      assignment of multiple alleles to either HLA-A*01:22 or HLA-A*01:81. These
      results suggest that careful considerations needed to be taken when using exome
      based HLA class I genotyping data and applying these results in clinical
      settings.

PMID- 27881844
TI  - Wide-Field Detected Fourier Transform CARS Microscopy.
AB  - We present a wide-field imaging implementation of Fourier transform coherent anti
      Stokes Raman scattering (wide-field detected FT-CARS) microscopy capable of
      acquiring high-contrast label-free but chemically specific images over the full
      vibrational 'fingerprint' region, suitable for a large field of view. Rapid
      resonant mechanical scanning of the illumination beam coupled with highly
      sensitive, camera-based detection of the CARS signal allows for fast and direct
      hyperspectral wide-field image acquisition, while minimizing sample damage.
      Intrinsic to FT-CARS microscopy, the ability to control the range of time-delays
      between pump and probe pulses allows for fine tuning of spectral resolution,
      bandwidth and imaging speed while maintaining full duty cycle. We outline the
      basic principles of wide-field detected FT-CARS microscopy and demonstrate how it
      can be used as a sensitive optical probe for chemically specific Raman imaging.

PMID- 27881845
TI  - Prevalence of overweight and malnutrition among ethnic minority children and
      adolescents in China, 1991-2010.
AB  - This study aimed to determine the trends in prevalence of childhood overweight
      and malnutrition in a large Chinese ethnic minority population from 1991 to 2010.
      In the Chinese National Survey on Students' Constitution and Health from 1991 to
      2010, multistage stratified sampling was conducted in the series of cross
      sectional studies. Participants were 7-18-year-old students randomly selected by
      sex and region, and included Han and 26 ethnic minorities. During the survey
      period, the overall prevalence of overweight increased from 5.8% to 13.5%, and
      malnutrition trend increased from 3.6% to 4.1% in ethnic minority children and
      adolescents. Moreover, Korean and Mongol children were more likely than Han
      children to be obese (Korean: RR = 1.52; 95% CI: 1.48-1.56; Mongol: RR = 1.24;
      95% CI: 1.20-1.28). Among these minorities, the Dongxiang and Li children were
      more likely to be malnourished (Li: RR = 1.47; 95% CI: 1.37-1.57; Dongxiang: RR =
      1.45; 95% CI: 1.34-1.58). Shui, Khalkhas, Lisu, and Monguor children were less
      likely to be overweight and malnourished compared with the Hans. The prevalence
      of overweight among ethnicities increased yearly while that for malnutrition has
      fluctuated over the past few decades.

PMID- 27881846
TI  - Naturally Occurring Fc-Dependent Antibody From HIV-Seronegative Individuals
      Promotes HIV-Induced IFN-alpha Production.
AB  - A majority of adults without HIV infection and with a low risk of HIV-exposure
      have plasma IgG antibodies that enhance the rate and magnitude of HIV-induced
      interferon alpha (IFN-alpha) production. Fc-dependent IgG-HIV complexes induce
      IFN-alpha rapidly and in high titers in response to HIV concentrations that are
      too low to otherwise stimulate an effective IFN-alpha response. IFN-alpha
      promoting antibody (IPA) counters HIV-specific inhibition of IFN-alpha
      production, and compensates for the inherent delay in IFN-alpha production common
      to HIV infection and other viruses. Naturally occurring IPA has the potential to
      initiate a potent IFN-alpha response early in the course of HIV mucosal invasion
      in time to terminate infection prior to the creation of a pool of persistently
      infected cells. The current study adds IPA as a mediator of an Fc-dependent
      antiviral state capable of preventing HIV infection.

PMID- 27881847
TI  - Epigenetic regulation of L-type voltage-gated Ca2+ channels in mesenteric
      arteries of aging hypertensive rats.
AB  - Accumulating evidence has shown that epigenetic regulation is involved in
      hypertension and aging. L-type voltage-gated Ca2+ channels (LTCCs), the dominant
      channels in vascular myocytes, greatly contribute to arteriole contraction and
      blood pressure (BP) control. We investigated the dynamic changes and epigenetic
      regulation of LTCC in the mesenteric arteries of aging hypertensive rats. LTCC
      function was evaluated by using microvascular rings and whole-cell patch-clamp in
      the mesenteric arteries of male Wistar-Kyoto rats and spontaneously hypertensive
      rats at established hypertension (3 month old) and an aging stage (16 month old),
      respectively. The expression of the LTCC alpha1C subunit was determined in the
      rat mesenteric microcirculation. The expression of miR-328, which targets alpha1C
      mRNA, and the DNA methylation status at the promoter region of the alpha1C gene
      (CACNA1C) were also determined. In vitro experiments were performed to assess
      alpha1C expression after transfection of the miR-328 mimic into cultured vascular
      smooth muscle cells (VSMCs). The results showed that hypertension superimposed
      with aging aggravated BP and vascular remodeling. Both LTCC function and
      expression were significantly increased in hypertensive arteries and
      downregulated with aging. miR-328 expression was inhibited in hypertension, but
      increased with aging. There was no significant difference in the mean DNA
      methylation of CACNA1C among groups, whereas methylation was enhanced in the
      hypertensive group at specific sites on a CpG island located upstream of the gene
      promoter. Overexpression of miR-328 inhibited the alpha1C level of cultured VSMCs
      within 48 h. The results of the present study indicate that the dysfunction of
      LTCCs may exert an epigenetic influence at both pre- and post-transcriptional
      levels during hypertension pathogenesis and aging progression. miR-328 negatively
      regulated LTCC expression in both aging and hypertension.

PMID- 27881849
TI  - Are diuretic additives fit for uncontrolled hypertensive patients receiving
      telmisartan and amlodipine treatment?

PMID- 27881848
TI  - Expression and methylation of circulating microRNA-510 in essential hypertension.
AB  - Hypertension (HTN) is one of the most common emerging disease in developing
      countries. It alters endothelial cell structure and function, resulting in
      several diseases, such as cardiovascular disease, peripheral vasculopathy,
      cerebrovascular disease and nephropathy. Although much progress has been made in
      researching HTN in recent years, early diagnosis and treatment of HTN are not yet
      satisfactory, and progression control/treatment is still poor. MicroRNAs are well
      known regulators of the physiological and developmental processes of HTN. Our
      results revealed that miR-510 was upregulated in blood samples from HTN patients,
      whereas no significant differences were observed in the control samples.
      Methylation analyses corroborated the miR-510 upregulation in patient samples.
      These results suggested that miR-510 can be used as a novel biomarker for
      diagnosis and as a new therapeutic target for HTN.

PMID- 27881850
TI  - Relationship between asymptomatic intra-cranial lesions and brachial-ankle pulse
      wave velocity in coronary artery disease patients without stroke.
AB  - Little is known about the significance of asymptomatic intra-cranial lesions
      (ICL) identified by brain MRI in coronary artery disease (CAD) patients. Silent
      cerebral lesions are suggested to be associated with arterial stiffness in
      healthy subjects. We investigated whether subclinical ICL are associated with
      arterial stiffness and the prognosis in CAD patients without medical history of
      cerebrovascular diseases. We recruited CAD patients who required percutaneous
      coronary intervention (PCI), did not meet exclusion criteria, and agreed with MRI
      before PCI. Subjects were divided into two groups according to the presence of
      ICL of cerebral microbleeds or lacunar infarction. Arterial stiffness was
      evaluated by brachial-ankle pulse wave velocity (baPWV). Clinical outcome was
      defined as a composite of cardiovascular death, non-fatal myocardial infarction,
      stroke, unstable angina and heart failure. In total, 149 patients underwent brain
      MRI. Patients with ICL (n=55) had significantly higher baPWV than those without
      ICL (1591-2204 vs. 1450-1956 cm per sec; P=0.009). A multivariate analysis showed
      that male sex (odds ratio (OR), 3.15; 95% confidence interval (CI), 1.38-7.20;
      P=0.006) and baPWV (OR, 1.001; 95% CI, 1.000-1.002; P=0.023) were predictors of
      ICL. In total, 12 patients experienced a cardiovascular event. The Kaplan-Meier
      analysis indicated a significantly higher incidence of cardiovascular events in
      patients with ICL (log-rank test: P=0.018). Multivariate Cox proportional hazards
      analyses indicated that ICL finding was a significant predictor of clinical
      outcome (hazard ratio, 3.41; 95% CI, 1.02-11.5; P=0.047). Patients with
      subclinical ICL had a higher baPWV and worse prognoses than those without ICL.

PMID- 27881852
TI  - Macrophage-derived exosomes induce inflammatory factors in endothelial cells
      under hypertensive conditions.
AB  - Hypertension is one of the most important cardiovascular risk factors and results
      in macrophage infiltration of blood vessels. However, how macrophages coordinate
      inflammatory responses with endothelial cells (ECs) remains unclear. In this
      study, we investigated whether exosomes upregulate the expression of inflammatory
      factors in ECs under hypertensive conditions. Hypertension was induced in rats by
      continuous infusion of angiotensin II (Ang II). Exosomes were purified from rat
      serum by density gradient and ultracentrifugation and used to stimulate human
      coronary artery ECs (HCAECs). Moreover, the interactions between HCAECs and
      exosomes from human THP-1-derived macrophages were analyzed. Administration of
      Ang II enhanced the expression of CD68, a macrophage marker, in rat hearts,
      suggesting enhanced infiltration of macrophages. In addition, the expression of
      intracellular adhesion molecule-1 (ICAM1) and plasminogen activator inhibitor-1
      (PAI-1), a proinflammatory factor, was increased in hypertensive rat hearts
      compared with control rats. CD68 protein expression and an increase in the
      expression of some exosome markers were detected in exosomes from hypertensive
      rat serum. Moreover, the exosomes upregulated the expression levels of ICAM1 and
      PAI-1 in HCAECs. The level of miR-17, a negative regulator of ICAM1 expression,
      was markedly decreased in exosomes from hypertensive rat serum compared with
      exosomes from control rats. Interestingly, Ang II-stimulated THP-1-derived
      exosomes also enhanced the expression of ICAM1 and PAI-1 and contained reduced
      levels of miR-17 compared with exosomes from unstimulated cells. These results
      suggest that inflammation of ECs under hypertensive conditions is caused, at
      least in part, by macrophage-derived exosomes.

PMID- 27881851
TI  - Relationships between 24-h blood pressure variability and 24-h central arterial
      pressure, pulse wave velocity and augmentation index in hypertensive patients.
AB  - Twenty-four-h blood pressure variability (BPV) predicts cardiovascular
      complications in hypertension, but its association with pulse wave indices
      (central arterial pressure, pulse wave velocity (PWV) and augmentation index
      (AIx)) is poorly understood. In the present study, we assessed the degree of the
      effect of 24-h BPV on 24-h pulse wave indices. Brachial blood pressure was
      measured non-invasively over the 24 h with an electronic, oscillometric,
      automated device (BPLab) in 661 uncomplicated treated or untreated hypertensive
      patients. Digitalized oscillometric waveforms were analyzed with a validated
      algorithm to obtain pulse wave indices. Twenty-four-h BPV was calculated as the
      unweighted (SDu) or weighted s.d. (SDw) of the mean blood pressure or as the
      average real variability (ARV). Twenty-four-h systolic BPV showed a direct and
      significant relationship with the central arterial systolic pressure (r=0.28 SDu,
      r=0.40 SDw, r=0.34 ARV), PWV (r=0.10 SDu, r=0.21 SDw, r=0.19 ARV) and AIx (r=0.17
      SDu, r=0.27 SDw, r=0.23 ARV). After adjustment for age, sex, body mass index,
      antihypertensive treatment and 24-h systolic blood pressure, the relationship
      lost some power but was still significant for all measures, except for the AIx.
      Pulse wave indices were higher in patients with high BPV than in those with low
      BPV: after adjustment, these differences were abolished for the AIx. The
      diastolic BPV showed a weak association with the pulse wave indices. In
      conclusion, in hypertensive patients, 24-h systolic BPV is moderately and
      independently associated with 24-h central arterial pressure and stiffness.

PMID- 27881853
TI  - Relationship between 24-h urine sodium/potassium ratio and central aortic
      systolic blood pressure in hypertensive patients.
AB  - Studies evaluating the relationship between measured 24-h urine sodium (24HUNa),
      potassium (24HUK) and aortic blood pressure (BP) are rare, and no such study has
      been performed with an Asian population. We evaluated the relationship between
      24HUNa, 24HUK, casual BP, 24-h ambulatory BP and aortic BP by analyzing data from
      524 participants with valid 24-h urine collection, 24-h ambulatory BP and central
      BP measurements (mean age 48.1+/-9.8 years, 193 men). Hypertension was defined as
      a 24-h ambulatory BP ?130/80 mm Hg or current treatment for hypertension (n=219).
      The participants with hypertension and high 24HUNa (mean 210.5+/-52.0 mmol  per
      day, range 151.0-432.0) showed higher 24-h systolic (P=0.037) and diastolic BP
      (P=0.037) and aortic systolic BP (AoSBP, P=0.038) than the participants with
      hypertension and low 24HUNa (mean 115.7+/-25.0 mmol per day, range 45.6-150.0),
      adjusted for confounders. The participants with hypertension and a high ratio of
      24HUNa and 24HUK (24HUNa/24HUK, mean 4.03+/-1.00, range 2.93-7.96) had higher
      AoSBP than the participants with hypertension and a low 24HUNa/24HUK ratio (mean
      2.13+/-0.54, range 0.53-2.91), adjusted for confounders (P=0.026). The
      participants with hypertension demonstrated a significant linear relationship
      between AoSBP and 24HUNa/24HUK ratio that was independent of 24HUNa, according to
      the multiple regression analysis (P=0.047). In hypertensive patients,
      24HUNa/24HUK was positively and more strongly related to AoSBP compared with
      24HUNa alone. The result indicates that high sodium and low potassium intake may
      increase the subsequent risk of cardiovascular disease by elevating AoSBP.

PMID- 27881855
TI  - CRF and the nucleus incertus: a node for integration of stress signals.

PMID- 27881854
TI  - The neural and computational bases of semantic cognition.
AB  - Semantic cognition refers to our ability to use, manipulate and generalize
      knowledge that is acquired over the lifespan to support innumerable verbal and
      non-verbal behaviours. This Review summarizes key findings and issues arising
      from a decade of research into the neurocognitive and neurocomputational
      underpinnings of this ability, leading to a new framework that we term controlled
      semantic cognition (CSC). CSC offers solutions to long-standing queries in
      philosophy and cognitive science, and yields a convergent framework for
      understanding the neural and computational bases of healthy semantic cognition
      and its dysfunction in brain disorders.

PMID- 27881857
TI  - Depressive symptoms, body composition and bone mass in young adults: a
      prospective cohort study.
AB  - BACKGROUND: An association between depression and obesity is well recognised, but
      longitudinal studies of depressive symptoms in adolescents as a predictor of body
      composition are lacking. OBJECTIVE: We examined depressive symptoms at age 14, 17
      and 20 years as predictors of lean, fat and bone mass at age 20 years in a birth
      cohort. SUBJECTS/METHODS: In 1161 participants (569 females) in the Western
      Australia Pregnancy Cohort (Raine) Study, depressive symptoms were assessed using
      the Beck Depression Inventory for Youth at age 14 and 17 years, and the
      Depression, Anxiety and Stress Scale 21 at age 20 years. Participants were
      further classified into two trajectories using latent class analysis:
      no/transient and persistent/recurrent depression. At age 20 years, lean body mass
      (LBM), fat body mass (FBM) and total body bone mass were measured by dual-energy
      X-ray absorptiometry. RESULTS: In females, accounting for age and lifestyle
      factors, depression scores at age 14 and 20 years were positively associated with
      body weight, body mass index (BMI), FBM and % FBM (r=0.110-0.184, P<0.05) but
      negatively correlated with % LBM (r=-0.120, P<0.05) at age 20 years. Females in
      the persistent/recurrent depression trajectory (n=99) had significantly higher
      body weight (+5.1 kg), BMI (+1.8 kg m-2), FBM (+3.9 kg) and % FBM (+2.2%) and
      significantly lower % LBM (-2.2%) at age 20 years than those with no/transient
      depression (n=470; all P<0.05). In males, depression scores at age 17 and 20
      years were negatively associated with LBM but not weight or BMI, and depression
      trajectory was not a predictor of body composition at age 20 years. Depression
      scores and trajectories did not predict bone mass in either males or females.
      CONCLUSIONS: Depressive symptoms and persistent/recurrent depression in
      adolescence are predictors of greater adiposity at age 20 years in females, but
      not males, but do not predict bone mass in either gender.

PMID- 27881858
TI  - Safety and efficacy of bariatric surgery in patients with advanced fibrosis.
AB  - BACKGROUND: Bariatric surgery is performed safely in non-alcoholic fatty liver
      disease (NAFLD) patients with minimal fibrosis (stage 1-2). However, the safety
      and potential benefits of bariatric surgery for NAFLD with advanced fibrosis
      (stage 3-4) remain unclear. This study was designed to compare the safety and
      efficacy of bariatric surgery in patients with biopsy proven advanced fibrosis to
      those with minimal fibrosis. METHODS: All patients who underwent bariatric
      surgery between 2005 and 2014 and had evidence of NAFLD with fibrosis score 3-4
      (advanced fibrosis) based on the staging system defined by Kleiner et al. on
      intraoperative liver biopsy were included and compared with patients who had
      fibrosis score 1-2 (minimal fibrosis). The groups were compared for length of
      hospital stay after bariatric surgery and incidence of postoperative
      complications over a follow-up period of 1 year. An improvement in hepatic
      function tests before and 1 year after surgery was used as a parameter to
      evaluate for NAFLD improvement. RESULTS: Ninety-nine patients with F3-4 (group 1)
      and 198 patients with F1-2 (group 2) were included. Mean age (51.9 vs 50.1 years)
      and body mass index (46.4 vs 46.5 kg m-2) were similar in the two groups. Median
      serum aspartate aminotransferase (43  vs 30 U l-1; normal 10-40 U l-1) and
      alanine aminotransferase (40.5 vs 34 U l-1; normal 10-50 U l-1) were
      significantly higher in group 1 and improved 1 year after surgery. Median length
      of hospital stay after surgery was higher in group 1 than that in group 2 (4 days
      vs 3 days; P-value=0.002). The proportion of patients developing postoperative
      complications over 1 year was similar in both groups (36.4% vs 32.8%; P
      value=0.54). CONCLUSIONS: Advanced fibrosis does not increase the risk of
      developing postoperative complications in medically optimized patients undergoing
      bariatric surgery. Improvement in serum transaminase levels suggests a reduction
      in hepatic necroinflammatory activity following bariatric surgery.

PMID- 27881861
TI  - Regenerative medicine: Engineered iPSCs for cartilage repair.

PMID- 27881856
TI  - Stress, glucocorticoids and memory: implications for treating fear-related
      disorders.
AB  - Glucocorticoid stress hormones are crucially involved in modulating mnemonic
      processing of emotionally arousing experiences. They enhance the consolidation of
      new memories, including those that extinguish older memories, but impair the
      retrieval of information stored in long-term memory. As strong aversive memories
      lie at the core of several fear-related disorders, including post-traumatic
      stress disorder and phobias, the memory-modulating properties of glucocorticoids
      have recently become of considerable translational interest. Clinical trials have
      provided the first evidence that glucocorticoid-based pharmacotherapies aimed at
      attenuating aversive memories might be helpful in the treatment of fear-related
      disorders. Here, we review important advances in the understanding of how
      glucocorticoids mediate stress effects on memory processes, and discuss the
      translational potential of these new conceptual insights.

PMID- 27881860
TI  - In-situ restoration of one-stage partial nitritation-anammox process deteriorated
      by nitrate build-up via elevated substrate levels.
AB  - The one-stage partial nitritation and anammox process (PN/A) has been a promising
      microbial process to remove ammonia from wastewater especially with low
      carbon/nitrogen ratio. The main breakdown was the deterioration caused by
      overgrowth of nitrite oxidizing bacteria (NOB) resulting effluent nitrate build
      up in the PN/A process. This study presented an in-situ restoring strategy for
      suppressing NOB activity in a one-stage granular PN/A system deteriorated over 2
      months, using elevated concentrations of substrates (ammonia and nitrite) under
      limited dissolved oxygen level. The results showed that the NOB activity was
      successfully suppressed after 56 days of restoration, and finally the ratio of
      produced nitrate/consumed ammonium was reduced from 36.8% to 7%. On day 66 the
      nitrogen removal rate obtained as 1.2 kg N/(m3.d). The high FA level (5-40 mg/L)
      and low dissolved oxygen (<0.13 mg/L) were responsible for NOB suppression. From
      quantitative PCR (qPCR) analysis, after this restoration, anammox bacteria had a
      widely growth, and AOB stay stable, but Nitrospira increase and Nitrobacter
      declined. High amount of NOB was still persistent in the granules, which was not
      easy to wash-out and threaten the deammonification performance.

PMID- 27881862
TI  - Rheumatoid arthritis: IL-23 assists the transition from autoimmunity to
      inflammatory disease.

PMID- 27881863
TI  - Epidemiology: The effects of AIDS on the prevalence of rheumatic diseases.

PMID- 27881859
TI  - Friends and social contexts as unshared environments: a discordant sibling
      analysis of obesity- and health-related behaviors in young adolescents.
AB  - OBJECTIVE: This study examines the contribution of best friends' weight and the
      peer social context (time spent alone versus with friends) as sources of unshared
      environment associated with variability in weight and health behaviors among
      weight-discordant siblings. METHODS: Pairs of same-sex biologic siblings (N=40
      pairs; ages 13-17) were originally recruited as part of a study evaluating
      putative factors contributing to differences in adiposity among weight-discordant
      siblings. Siblings were asked to bring their best friends to the laboratory and
      siblings and friends' height and weight were objectively measured. Siblings also
      completed multi-pass dietary recalls to assess energy intake and sugar sweetened
      beverage (SSB) consumption. Siblings' physical activity was measured using
      accelerometry. Experience sampling methodology was used to assess sedentary
      behaviors/screen time and the number of occasions siblings spent alone and in the
      presence of friends. Multilevel models were used to estimate the relationships
      between predictors (best friends' zBMI, time spent alone or with friends) and
      outcomes (siblings' zBMI and obesity-related health behaviors). RESULTS: Best
      friends' zBMI was the best predictor of participants' zBMI, even when controlling
      for child's birth weight. Best friends' weight (zBMI) further predicted
      participants' SSB intake and time engaged in sedentary behaviors. Being active
      with friends was positively associated with participants' overall physical
      activity, whereas spending time alone was negatively associated with
      accelerometer counts regardless of siblings' adiposity. CONCLUSIONS: A friends'
      weight and the social context are unshared environmental factors associated with
      variability in adiposity among biologically-related weight-discordant siblings.

PMID- 27881865
TI  - Bandicoot fossils and DNA elucidate lineage antiquity amongst xeric-adapted
      Australasian marsupials.
AB  - Bandicoots (Peramelemorphia) are a unique order of Australasian marsupials whose
      sparse fossil record has been used as prima facie evidence for climate change
      coincident faunal turnover. In particular, the hypothesized replacement of
      ancient rainforest-dwelling extinct lineages by antecedents of xeric-tolerant
      extant taxa during the late Miocene (~10 Ma) has been advocated as a broader
      pattern evident amongst other marsupial clades. Problematically, however, this is
      in persistent conflict with DNA phylogenies. We therefore determine the pattern
      and timing of bandicoot evolution using the first combined morphological + DNA
      sequence dataset of Peramelemorphia. In addition, we document a remarkably
      archaic new fossil peramelemorphian taxon that inhabited a latest Quaternary
      mosaic savannah-riparian forest ecosystem on the Aru Islands of Eastern
      Indonesia. Our phylogenetic analyses reveal that unsuspected dental homoplasy and
      the detrimental effects of missing data collectively obscure stem bandicoot
      relationships. Nevertheless, recalibrated molecular clocks and multiple ancestral
      area optimizations unanimously infer an early diversification of modern xeric
      adapted forms. These probably originated during the late Palaeogene (30-40 Ma)
      alongside progenitors of other desert marsupials, and thus occupied seasonally
      dry heterogenous habitats long before the onset of late Neogene aridity.

PMID- 27881864
TI  - Mass spectrometry imaging: a novel technology in rheumatology.
AB  - Mass spectrometry imaging (MSI) is used to determine the relative abundance and
      spatial distribution of biomolecules such as peptides, proteins, lipids and other
      organic compounds in tissue sections by their molecular masses. This technique
      provides a sensitive and label-free approach for high-resolution imaging, and is
      currently used in an increasing number of biomedical applications such as
      biomarker discovery, tissue classification and drug monitoring. Owing to
      technological advances in the past 5 years in diverse MSI strategies, this
      technology is expected to become a standard tool in clinical practice and
      provides information complementary to that obtained using existing methods. Given
      that MSI is able to extract mass-spectral signatures from pathological tissue
      samples, this technique provides a novel platform to study joint-related tissues
      affected by rheumatic diseases. In rheumatology, MSI has been performed on
      articular cartilage, synovium and bone to increase the understanding of articular
      destruction and to characterize diagnostic and prognostic biomarkers for
      osteoarthritis, rheumatoid arthritis and osteoporosis. In this Review, we provide
      an overview of MSI technology and of the studies in which joint tissues have been
      analysed by use of this methodology. This approach might increase knowledge of
      rheumatic pathologies and ultimately prompt the development of targeted
      strategies for their management.

PMID- 27881866
TI  - "Hearing faces and seeing voices": Amodal coding of person identity in the human
      brain.
AB  - Recognizing familiar individuals is achieved by the brain by combining cues from
      several sensory modalities, including the face of a person and her voice. Here we
      used functional magnetic resonance (fMRI) and a whole-brain, searchlight multi
      voxel pattern analysis (MVPA) to search for areas in which local fMRI patterns
      could result in identity classification as a function of sensory modality. We
      found several areas supporting face or voice stimulus classification based on
      fMRI responses, consistent with previous reports; the classification maps
      overlapped across modalities in a single area of right posterior superior
      temporal sulcus (pSTS). Remarkably, we also found several cortical areas, mostly
      located along the middle temporal gyrus, in which local fMRI patterns resulted in
      identity "cross-classification": vocal identity could be classified based on fMRI
      responses to the faces, or the reverse, or both. These findings are suggestive of
      a series of cortical identity representations increasingly abstracted from the
      input modality.

PMID- 27881868
TI  - Seed sojourn and fast viability loss constrain seedling production of a prominent
      riparian protection plant Salix variegata Franch.
AB  - Salix variegata Franch, a prominent plant applied in riparian shelter vegetation
      in Three Gorges reservoir region of China, produces many seeds every year but
      generates only a few or no seedlings. Whether the low seedling production of S.
      variegata is caused by seed sterility or by rapid loss of seed viability remains
      unknown. We investigated the sojourn time of mature seeds in capsules produced in
      early, mid, and late reproductive season and the germinability of mature seeds
      fresh or stored after different period of time. The sojourn time of seeds in
      capsules was 2.89, 3.95, and 4.72 days in early, mid, and late reproductive
      season, respectively. The maximal germination percentage of non-stored fresh
      seeds produced in early, mid, and late reproductive season was 93.33%, 78.67%,
      and 40%, respectively, which indicates mature seeds were not sterile. The longest
      viability-retaining time of seeds produced in early, mid, and late reproductive
      season was only 8, 16, 16 days, respectively, indicating that mature seeds of S.
      variegata lost viability very rapidly. Mature seeds possessed good viability, but
      their rapid viability loss caused the low seedling production and hampered the
      population growth of S. variegata in the riparian area of Three Gorges reservoir
      region.

PMID- 27881867
TI  - Endothelial cell colony forming units derived from malignant breast diseases are
      resistant to tumor necrosis factor-alpha-induced apoptosis.
AB  - Mobilisation of endothelial progenitor cells (EPCs) from the bone marrow is a
      crucial step in the formation of de novo blood vessels, and levels of peripheral
      blood EPCs have been shown to be elevated in certain malignant states. Using flow
      cytometry and a Hill-based colony forming unit (CFU) assay, the present study
      indicated that higher levels of CD34 and vascular endothelial growth factor
      receptor 2 (VEGFR2) double-positive EPCs, as well as increased formation of
      endothelial cell colony-forming units (EC-CFUs) are associated with benign and
      malignant breast diseases, providing possible indicators for breast disease
      detection. Gene expression profiles revealed a genetic difference between CD34+
      VEGFR2+ EPCs and EC-CFUs. Decreased expression of tumour necrosis factor receptor
      2 (TNFR2) signalling-related genes and inhibition of tumour necrosis factor (TNF)
      induced signalling were demonstrated in EC-CFUs derived from patients with
      malignant breast disease in comparison with those from healthy controls.
      Interestingly, our data provided the first evidence that EC-CFUs derived from
      patients with malignant breast disease were resistant to TNF-alpha-induced
      apoptosis, indicating a plausible target for future therapeutic interventions.

PMID- 27881869
TI  - Netrin-1-Induced Stem Cell Bioactivity Contributes to the Regeneration of Injured
      Tissues via the Lipid Raft-Dependent Integrin alpha6beta4 Signaling Pathway.
AB  - Netrin-1 (Ntn-1) is a multifunctional neuronal signaling molecule; however, its
      physiological significance, which improves the tissue-regeneration capacity of
      stem cells, has not been characterized. In the present study, we investigate the
      mechanism by which Ntn-1 promotes the proliferation of hUCB-MSCs with regard to
      the regeneration of injured tissues. We found that Ntn-1 induces the
      proliferation of hUCB-MSCs mainly via Inalpha6beta4 coupled with c-Src. Ntn-1
      induced the recruitment of NADPH oxidases and Rac1 into membrane lipid rafts to
      facilitate ROS production. The Inalpha6beta4 signaling of Ntn-1 through ROS
      production is uniquely mediated by the activation of SP1 for cell cycle
      progression and the transcriptional occupancy of SP1 on the VEGF promoter.
      Moreover, Ntn-1 has the ability to induce the F-actin reorganization of hUCB-MSCs
      via the Inalpha6beta4 signaling pathway. In an in vivo model, transplantation of
      hUCB-MSCs pre-treated with Ntn-1 enhanced the skin wound healing process, where
      relatively more angiogenesis was detected. The potential effect of Ntn-1 on
      angiogenesis is further verified by the mouse hindlimb ischemia model, where the
      pre-activation of hUCB-MSCs with Ntn-1 significantly improved vascular
      regeneration. These results demonstrate that Ntn-1 plays an important role in the
      tissue regeneration process of hUCB-MSC via the lipid raft-mediated Inalpha6beta4
      signaling pathway.

PMID- 27881870
TI  - Antibody-antigen kinetics constrain intracellular humoral immunity.
AB  - During infection with non-enveloped viruses, antibodies stimulate immunity from
      inside cells by activating the cytosolic Fc receptor TRIM21. This intracellular
      humoral response relies on opsonized viral particles reaching the cytosol intact
      but the antigenic and kinetic constraints involved are unknown. We have solved
      the structure of a potent TRIM21-dependent neutralizing antibody in complex with
      human adenovirus 5 hexon and show how these properties influence immune activity.
      Structure-guided mutagenesis was used to generate antibodies with 20,000-fold
      variation in affinity, on-rates that differ by ~50-fold and off-rates by >175
      fold. Characterization of these variants during infection revealed that TRIM21
      dependent neutralization and NFkappaB activation was largely unaffected by on
      rate kinetics. In contrast, TRIM21 antiviral activity was exquisitely dependent
      upon off-rate, with sub-MUM affinity antibodies nevertheless unable to stimulate
      signaling because of fast dissociation kinetics. These results define the
      antibody properties required to elicit an efficient intracellular immune response
      during viral infection.

PMID- 27881871
TI  - Diagnosis and relapse: cytogenetically normal acute myelogenous leukemia without
      FLT3-ITD or MLL-PTD.

PMID- 27881873
TI  - Induction of iron excess restricts malignant plasma cells expansion and
      potentiates bortezomib effect in models of multiple myeloma.

PMID- 27881874
TI  - Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis.
AB  - We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal
      hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A
      (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment.
      Diagnostic, complete remission (CR) and relapse samples were sequenced for 34
      leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH
      was found in 40 patients (23%) and was associated with clonal hematopoiesis of
      indeterminate potential years before AML, older age, secondary AML and more
      frequent MDS-type co-mutations (TET2, RUNX1 and EZH2). In 82% of AML patients
      with LM-CH, the preleukemic clone was refractory to chemotherapy and was the
      founding clone for relapse. Both LM-CH and non-LM-CH MRD-positive AML patients
      who achieved CR had a high risk of relapse after 10 years (75% and 75%,
      respectively) compared with patients without clonal hematopoiesis in CR with
      negative MRD (27% relapse rate). Long-term survival of patients with LM-CH was
      only seen after allogeneic hematopoietic stem cell transplantation (HSCT). We
      define AML patients with LM-CH as a distinct high-risk group of AML patients that
      can be identified at diagnosis through mutation analysis in T cells and should be
      considered for HSCT.

PMID- 27881872
TI  - In vitro and in vivo assessment of direct effects of simulated solar and galactic
      cosmic radiation on human hematopoietic stem/progenitor cells.
AB  - Future deep space missions to Mars and near-Earth asteroids will expose
      astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray
      (GCR) radiation, and likely one or more solar particle events (SPEs). Given the
      inherent radiosensitivity of hematopoietic cells and short latency period of
      leukemias, space radiation-induced hematopoietic damage poses a particular threat
      to astronauts on extended missions. We show that exposing human hematopoietic
      stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated
      high-energy protons and iron ions leads to the following: (1) introduces
      mutations that are frequently located within genes involved in hematopoiesis and
      are distinct from those induced by gamma-radiation; (2) markedly reduces in vitro
      colony formation; (3) markedly alters engraftment and lineage commitment in vivo;
      and (4) leads to the development, in vivo, of what appears to be T-ALL.
      Sequential exposure to protons and iron ions (as typically occurs in deep space)
      proved far more deleterious to HSC genome integrity and function than either
      particle species alone. Our results represent a critical step for more accurately
      estimating risks to the human hematopoietic system from space radiation,
      identifying and better defining molecular mechanisms by which space radiation
      impairs hematopoiesis and induces leukemogenesis, as well as for developing
      appropriately targeted countermeasures.

PMID- 27881875
TI  - Loss of p300 accelerates MDS-associated leukemogenesis.
AB  - The role that changes in DNA methylation and histone modifications have in human
      malignancies is poorly understood. p300 and CREB-binding protein (CBP), two
      distinct but highly homologous lysine acetyltransferases, are mutated in several
      cancers, suggesting their role as tumor suppressors. In the current study, we
      found that deletion of p300, but not CBP, markedly accelerated the leukemogenesis
      ofNup98-HoxD13 (NHD13) transgenic mice, an animal model that phenotypically
      copies human myelodysplastic syndrome (MDS). p300 deletion restored the ability
      of NHD13 expressing hematopoietic stem and progenitor cells (HSPCs) to self-renew
      in vitro, and to expand in vivo, with an increase in stem cell symmetric self
      renewal divisions and a decrease in apoptosis. Furthermore, loss of p300, but not
      CBP, promoted cytokine signaling, including enhanced activation of the MAPK and
      JAK/STAT pathways in the HSPC compartment. Altogether, our data indicate that
      p300 has a pivotal role in blocking the transformation of MDS to acute myeloid
      leukemia, a role distinct from that of CBP.

PMID- 27881876
TI  - The efficacy of high-throughput sequencing and target enrichment on charred
      archaeobotanical remains.
AB  - The majority of archaeological plant material is preserved in a charred state.
      Obtaining reliable ancient DNA data from these remains has presented challenges
      due to high rates of nucleotide damage, short DNA fragment lengths, low
      endogenous DNA content and the potential for modern contamination. It has been
      suggested that high-throughput sequencing (HTS) technologies coupled with DNA
      enrichment techniques may overcome some of these limitations. Here we report the
      findings of HTS and target enrichment on four important archaeological crops
      (barley, grape, maize and rice) performed in three different laboratories,
      presenting the largest HTS assessment of charred archaeobotanical specimens to
      date. Rigorous analysis of our data - excluding false-positives due to background
      contamination or incorrect index assignments - indicated a lack of endogenous DNA
      in nearly all samples, except for one lightly-charred maize cob. Even with target
      enrichment, this sample failed to yield adequate data required to address
      fundamental questions in archaeology and biology. We further reanalysed part of
      an existing dataset on charred plant material, and found all purported endogenous
      DNA sequences were likely to be spurious. We suggest these technologies are not
      suitable for use with charred archaeobotanicals and urge great caution when
      interpreting data obtained by HTS of these remains.

PMID- 27881877
TI  - Exercise training attenuates renovascular hypertension partly via RAS- ROS-
      glutamate pathway in the hypothalamic paraventricular nucleus.
AB  - Exercise training (ExT) has been reported to benefit hypertension; however, the
      exact mechanisms involved are unclear. We hypothesized that ExT attenuates
      hypertension, in part, through the renin-angiotensin system (RAS), reactive
      oxygen species (ROS), and glutamate in the paraventricular nucleus (PVN). Two
      kidney, one-clip (2K1C) renovascular hypertensive rats were assigned to sedentary
      (Sed) or treadmill running groups for eight weeks. Dizocilpine (MK801), a
      glutamate receptor blocker, or losartan (Los), an angiotensin II type1 receptor
      (AT1-R) blocker, were microinjected into the PVN at the end of the experiment. We
      found that 2K1C rats had higher mean arterial pressure (MAP) and renal
      sympathetic nerve activity (RSNA). These rats also had excessive oxidative stress
      and overactivated RAS in PVN. Eight weeks of ExT significantly decreased MAP and
      RSNA in 2K1C hypertensive rats. ExT inhibited angiotensin-converting enzyme
      (ACE), AT1-R, and glutamate in the PVN, and angiotensin II (ANG II) in the
      plasma. Moreover, ExT attenuated ROS by augmenting copper/zinc superoxide
      dismutase (Cu/Zn-SOD) and decreasing p47phox and gp91phox in the PVN. MK801or Los
      significantly decreased blood pressure in rats. Together, these findings suggest
      that the beneficial effects of ExT on renovascular hypertension may be, in part,
      through the RAS-ROS-glutamate pathway in the PVN.

PMID- 27881880
TI  - Spintronics.

PMID- 27881879
TI  - SCOUT: simultaneous time segmentation and community detection in dynamic
      networks.
AB  - Many evolving complex real-world systems can be modeled via dynamic networks. An
      important problem in dynamic network research is community detection, which finds
      groups of topologically related nodes. Typically, this problem is approached by
      assuming either that each time point has a distinct community organization or
      that all time points share a single community organization. The reality likely
      lies between these two extremes. To find the compromise, we consider community
      detection in the context of the problem of segment detection, which identifies
      contiguous time periods with consistent network structure. Consequently, we
      formulate a combined problem of segment community detection (SCD), which
      simultaneously partitions the network into contiguous time segments with
      consistent community organization and finds this community organization for each
      segment. To solve SCD, we introduce SCOUT, an optimization framework that
      explicitly considers both segmentation quality and partition quality. SCOUT
      addresses limitations of existing methods that can be adapted to solve SCD, which
      consider only one of segmentation quality or partition quality. In a thorough
      evaluation, SCOUT outperforms the existing methods in terms of both accuracy and
      computational complexity. We apply SCOUT to biological network data to study
      human aging.

PMID- 27881878
TI  - Gene regulatory networks in neural cell fate acquisition from genome-wide
      chromatin association of Geminin and Zic1.
AB  - Neural cell fate acquisition is mediated by transcription factors expressed in
      nascent neuroectoderm, including Geminin and members of the Zic transcription
      factor family. However, regulatory networks through which this occurs are not
      well defined. Here, we identified Geminin-associated chromatin locations in
      embryonic stem cells and Geminin- and Zic1-associated locations during neural
      fate acquisition at a genome-wide level. We determined how Geminin deficiency
      affected histone acetylation at gene promoters during this process. We integrated
      these data to demonstrate that Geminin associates with and promotes histone
      acetylation at neurodevelopmental genes, while Geminin and Zic1 bind a shared
      gene subset. Geminin- and Zic1-associated genes exhibit embryonic nervous system
      enriched expression and encode other regulators of neural development. Both
      Geminin and Zic1-associated peaks are enriched for Zic1 consensus binding motifs,
      while Zic1-bound peaks are also enriched for Sox3 motifs, suggesting co
      regulatory potential. Accordingly, we found that Geminin and Zic1 could
      cooperatively activate the expression of several shared targets encoding
      transcription factors that control neurogenesis, neural plate patterning, and
      neuronal differentiation. We used these data to construct gene regulatory
      networks underlying neural fate acquisition. Establishment of this molecular
      program in nascent neuroectoderm directly links early neural cell fate
      acquisition with regulatory control of later neurodevelopment.

PMID- 27881882
TI  - Depletion region surface effects in electron beam induced current measurements.
AB  - Electron beam induced current (EBIC) is a powerful characterization technique
      which offers the high spatial resolution needed to study polycrystalline solar
      cells. Current models of EBIC assume that excitations in the p-n junction
      depletion region result in perfect charge collection efficiency. However we find
      that in CdTe and Si samples prepared by focused ion beam (FIB) milling, there is
      a reduced and nonuniform EBIC lineshape for excitations in the depletion region.
      Motivated by this, we present a model of the EBIC response for excitations in the
      depletion region which includes the effects of surface recombination from both
      charge-neutral and charged surfaces. For neutral surfaces we present a simple
      analytical formula which describes the numerical data well, while the charged
      surface response depends qualitatively on the location of the surface Fermi level
      relative to the bulk Fermi level. We find the experimental data on FIB-prepared
      Si solar cells is most consistent with a charged surface, and discuss the
      implications for EBIC experiments on polycrystalline materials.

PMID- 27881881
TI  - Spintronic Nanodevices for Bioinspired Computing.
AB  - Bioinspired hardware holds the promise of low-energy, intelligent, and highly
      adaptable computing systems. Applications span from automatic classification for
      big data management, through unmanned vehicle control, to control for biomedical
      prosthesis. However, one of the major challenges of fabricating bioinspired
      hardware is building ultra-high-density networks out of complex processing units
      interlinked by tunable connections. Nanometer-scale devices exploiting spin
      electronics (or spintronics) can be a key technology in this context. In
      particular, magnetic tunnel junctions (MTJs) are well suited for this purpose
      because of their multiple tunable functionalities. One such functionality, non
      volatile memory, can provide massive embedded memory in unconventional circuits,
      thus escaping the von-Neumann bottleneck arising when memory and processors are
      located separately. Other features of spintronic devices that could be beneficial
      for bioinspired computing include tunable fast nonlinear dynamics, controlled
      stochasticity, and the ability of single devices to change functions in different
      operating conditions. Large networks of interacting spintronic nanodevices can
      have their interactions tuned to induce complex dynamics such as synchronization,
      chaos, soliton diffusion, phase transitions, criticality, and convergence to
      multiple metastable states. A number of groups have recently proposed bioinspired
      architectures that include one or several types of spintronic nanodevices. In
      this paper, we show how spintronics can be used for bioinspired computing. We
      review the different approaches that have been proposed, the recent advances in
      this direction, and the challenges toward fully integrated spintronics
      complementary metal-oxide-semiconductor (CMOS) bioinspired hardware.

PMID- 27881883
TI  - Aquatic methane dynamics in a human-impacted river-floodplain of the Danube.
AB  - River-floodplain systems are characterized by changing hydrological connectivity
      and variability of resources delivered to floodplain water bodies. Although the
      importance of hydrological events has been recognized, the effect of flooding on
      CH4 concentrations and emissions from European, human-impacted river-floodplains
      is largely unknown. This study evaluates aquatic concentrations and emissions of
      CH4 from a highly modified, yet partly restored river-floodplain system of the
      Danube near Vienna (Austria). We covered a broad range of hydrological
      conditions, including a 1-yr flood event in 2012 and a 100-yr flood in 2013. Our
      findings demonstrate that river-floodplain waters were supersaturated with CH4,
      hence always serving as a source of CH4 to the atmosphere. Hydrologically
      isolated habitats in general have higher concentrations and produce higher fluxes
      despite lower physically defined velocities. During surface connection, however,
      CH4 is exported from the floodplain to the river, suggesting that the main
      channel serves as an "exhaust pipe" for the floodplain. This mechanism was
      especially important during the 100-yr flood, when a clear pulse of CH4 was
      flushed from the floodplain with surface floodwaters. Our results emphasize the
      importance of floods differing in magnitude for methane evasion from river
      floodplains; 34% more CH4 was emitted from the entire system during the year with
      the 100-yr flood compared to a hydrologically "normal" year. Compared to the main
      river channel, semiisolated floodplain waters were particularly strong sources of
      CH4. Our findings also imply that the predicted increased frequency of extreme
      flooding events will have significant consequences for methane emission from
      river-floodplain systems.

PMID- 27881884
TI  - Towards a standard for the dynamic measurement of pressure based on laser
      absorption spectroscopy.
AB  - We describe an approach for creating a standard for the dynamic measurement of
      pressure based on the measurement of fundamental quantum properties of molecular
      systems. From the linewidth and intensities of ro-vibrational transitions we plan
      on making an accurate determination of pressure and temperature. The goal is to
      achieve an absolute uncertainty for time-varying pressure of 5 % with a
      measurement rate of 100 kHz, which will in the future serve as a method for the
      traceable calibration of pressure sensors used in transient processes. To
      illustrate this concept we have used wavelength modulation spectroscopy (WMS),
      due to inherent advantages over direct absorption spectroscopy, to perform rapid
      measurements of carbon dioxide in order to determine the pressure. The system
      records the full lineshape profile of a single ro-vibrational transition of CO2
      at a repetition rate of 4 kHz and with a systematic measurement uncertainty of 12
      % for the linewidth measurement. A series of pressures were measured at a rate of
      400 Hz (10 averages) and from these measurements the linewidth was determined
      with a relative uncertainty of about 0.5 % on average. The pressures measured
      using WMS have an average difference of 0.6 % from the absolute pressure measured
      with a capacitance diaphragm sensor.

PMID- 27881885
TI  - Acyclic nucleoside phosphonates containing the amide bond.
AB  - ABSTRACT: To study the influence of a linker rigidity and donor-acceptor
      properties, the P-CH2-O-CHR- fragment in acyclic nucleoside phosphonates (e.g.,
      acyclovir, tenofovir) was replaced by the P-CH2-HN-C(O)- residue. The respective
      phosphonates were synthesized in good yields by coupling the straight chain of
      omega-aminophosphonates and nucleobase-derived acetic acids with EDC. Based on
      the 1H and 13C NMR data, the unrestricted rotation within the methylene and 1,2
      ethylidene linkers in phosphonates from series a and b was confirmed. For
      phosphonates containing 1,3-propylidene (series c) fragments, antiperiplanar
      disposition of the bulky O,O-diethylphosphonate and substituted amidomethyl
      groups was established. The synthesized ANPs P-X-HNC(O)-CH2B (X = CH2, CH2CH2,
      CH2CH2CH2, CH2OCH2CH2) appeared inactive in antiviral assays against a wide
      variety of DNA and RNA viruses at concentrations up to 100 MUM while marginal
      antiproliferative activity (L1210 cells, IC50 = 89 +/- 16 MUM and HeLa cells,
      IC50 = 194 +/- 19 MUM) was noticed for the analog derived from (5-fluorouracyl-1
      yl)acetic acid and O,O-diethyl (2-aminoethoxy)methylphosphonate. GRAPHICAL
      ABSTRACT: 

PMID- 27881887
TI  - Changes in Sexuality, Body Image and Health Related Quality of Life in Patients
      Treated for Hematologic Malignancies: A Longitudinal Study.
AB  - Longitudinal studies exploring sexuality, body image and health-related quality
      of life (HRQoL) are lacking in patients treated with chemo- or chemoimmuno
      therapy for hematologic malignancies. The aim was to describe and explore changes
      in sexuality, body image and HRQoL in patients treated for hematologic
      malignancies, from baseline until 6 months after treatment. Twenty patients above
      45 years (median age 62) treated for DLBCL, CLL or AML participated. Data were
      collected at baseline, 1- and 6-months after treatment by means of three
      instruments: SAQ-S, BIS and EORTC QLQ-C30. The results showed that patients'
      sexuality was negatively affected 1 month after treatment, but after 6 months the
      patient reported scores had returned almost entirely to baseline scores. Body
      image was slight negatively affected after 1 month and after 6 months, 50 %
      reported that body image was not affected at all. Regarding HRQoL, patients
      reported gradually improved scores during the study period. Regression analysis
      showed that changes in sexuality and body image seemed to influence changes in
      HRQoL. This study has shown changes in sexuality, body image and HRQoL over time
      in patients above age 45 treated for hematologic malignancies. One month after
      treatment all three areas becomes negatively affected, and thereafter the
      patients' scores recovered to a great extent regarding these issues within 6
      months. Sexuality and body image seem to be important aspects of HRQoL for these
      patients and need to be integrated in the cancer rehabilitation during and after
      treatment.

PMID- 27881890
TI  - Co-management as a Catalyst: Pathways to Post-colonial Forestry in the Klamath
      Basin, California.
AB  - Co-management frameworks are intended to facilitate sustainable resource
      management and more equitable power sharing between state agencies and Indigenous
      communities. However, there is significant debate about who benefits from co
      management in practice. This article addresses two competing perspectives in the
      literature, which alternately portrays co-management as an instrument for co
      optation or for transformation. Through a case study of co-management
      negotiations involving the Karuk Tribe and the U.S. Forest Service in the Klamath
      Basin of Northern California, this study examines how Indigenous communities use
      co-management to build greater equity in environmental decision-making, despite
      its limitations. The concept of pivot points is developed to describe how
      Indigenous communities like the Karuk Tribe are simultaneously following existing
      state policies and subverting them to shift federal forest management. The pivot
      point analytic demonstrates one mechanism by which communities are addressing
      Indigenous self-determination goals and colonial legacies through environmental
      policy and management.

PMID- 27881888
TI  - Effects of Ramipril and Telmisartan on Plasma Concentrations of Low Molecular
      Weight and Protein Thiols and Carotid Intima Media Thickness in Patients with
      Chronic Kidney Disease.
AB  - Hypertension, a common feature in chronic kidney disease (CKD), is an independent
      risk factor for CKD progression and cardiovascular disease. Although inhibitors
      of the renin-angiotensin system (RAS) exert salutary effects on blood pressure
      control and proteinuria in CKD patients, their activity towards traditional and
      novel oxidative markers is largely unknown. We studied the effects of 6-month
      treatment with telmisartan versus a combination of telmisartan and ramipril on
      plasma concentrations of low molecular mass (LMW, including homocysteine and
      cysteine) and protein thiols (PSH) plasma concentration and their relationships
      with carotid intima media thickness (IMT), in 24 hypertensive CKD patients (age
      60 +/- 12 years, 8 females and 16 males). Pretreatment PSH concentrations were
      independently associated with IMT (r = -0.42, p = 0.039). Neither treatment
      affected plasma LMW thiols, in both reduced and total form. By contrast, both
      treatments increased PSH plasma concentrations and reduced IMT, although
      significant differences were only observed in the combined treatment group. Our
      results suggest that the beneficial effects of combined RAS inhibitor treatment
      on IMT in hypertensive CKD patients may be mediated by a reduction of oxidative
      stress markers, particularly PSH.

PMID- 27881886
TI  - Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American
      Ophthalmological Society Thesis).
AB  - PURPOSE: To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number
      variations (ie, gene duplications and triplications) in the pathophysiology of
      various open-angle glaucomas. METHODS: In previous studies, we discovered that
      copy-number variations in the TBK1 gene are associated with normal-tension
      glaucoma. Here, we investigated the prevalence of copy-number variations in
      cohorts of patients with other open-angle glaucomas-juvenile-onset open-angle
      glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and
      steroid-induced glaucoma (n=79)-using a quantitative polymerase chain reaction
      assay. RESULTS: No TBK1 gene copy-number variations were detected in patients
      with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced
      glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225
      exfoliation glaucoma patients. CONCLUSIONS: TBK1 gene copy-number variations
      (gene duplications and triplications) have been previously associated with normal
      tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1
      copy-number variation in a patient with exfoliation glaucoma, which is the first
      example of a TBK1 mutation in a glaucoma patient with a diagnosis other than
      normal-tension glaucoma. A broader phenotypic range may be associated with TBK1
      copy-number variations, although mutations in this gene are most often detected
      in patients with normal-tension glaucoma.

PMID- 27881889
TI  - Expression of CAF-Related Proteins Is Associated with Histologic Grade of Breast
      Phyllodes Tumor.
AB  - Purpose. The purpose of this study was to investigate the expression of cancer
      associated fibroblast- (CAF-) related proteins and the implications in breast
      phyllodes tumor (PT). Methods. Tissue microarrays of 194 PT cases (151 benign PT,
      27 borderline PT, and 16 malignant PT) were constructed. We performed
      immunohistochemical staining for CAF-related proteins (podoplanin, prolyl 4
      hydroxylase, FAPalpha, S100A4, PDGFR alpha/beta, and NG2) and analyzed the
      results according to clinicopathologic parameters. Results. Expression of
      PDGFRalpha and PDGFRbeta in the stromal component increased with increasing
      histologic grade of PT (p = 0.003 and p = 0.034, resp.). Among clinicopathologic
      parameters, only expression of FAPalpha in stroma was associated with distant
      metastasis (p = 0.002). In univariate analysis, stromal expression of PDGFRalpha
      was associated with shorter overall survival (p = 0.002). In Cox multivariate
      analysis, stromal overgrowth and PDGFRalpha stromal positivity were associated
      with shorter overall survival (p = 0.006 and p = 0.050, resp.). Furthermore,
      expression of PDGFRbeta in stroma was associated with shorter overall survival in
      patients with malignant PT (p = 0.041). Conclusion. Stromal expression of
      PDGFRalpha and PDGFRbeta increased with increasing histologic grade of PT. In
      addition, PDGFR stromal positivity was associated with shorter overall survival.
      These results suggest that CAFs are associated with breast PT progression.

PMID- 27881892
TI  - Income Inequality, Income, and Internet Searches for Status Goods: A Cross
      National Study of the Association Between Inequality and Well-Being.
AB  - Is there a positive association between a nation's income inequality and concerns
      with status competition within that nation? Here we use Google Correlate and
      Google Trends to examine frequency of internet search terms and find that people
      in countries in which income inequality is high search relatively more frequently
      for positional brand names such as Prada, Louis Vuitton, or Chanel. This tendency
      is stronger among well-developed countries. We find no evidence that income alone
      is associated with searches for positional goods. We also present evidence that
      the concern with positional goods does not reflect non-linear effects of income
      on consumer spending, either across nations or (extending previous findings that
      people who live in unequal US States search more for positional goods) within the
      USA. It is concluded that income inequality is associated with greater concerns
      with positional goods, and that this concern is reflected in internet searching
      behaviour.

PMID- 27881891
TI  - Smaller Saami Herding Groups Cooperate More in a Public Goods Experiment.

PMID- 27881893
TI  - What Predicts Adolescent Delinquent Behavior in Hong Kong? A Longitudinal Study
      of Personal and Family Factors.
AB  - Using four waves of data from Secondary 1 to Secondary 4 (N = 3328 students at
      Wave 1), this study examined the development of delinquent behavior and its
      relationships with economic disadvantage, family non-intactness, family quality
      of life (i.e., family functioning) and personal well-being (i.e., positive youth
      development) among Hong Kong adolescents. Individual growth curve models revealed
      that delinquent behavior increased during this period, and adolescents living in
      non-intact families (vs. intact families) reported higher initial levels of
      delinquent behavior while those living in poor families (vs. non-poor families)
      showed a greater increase in delinquent behavior. In addition, with the
      demographic factors controlled, the initial levels of family quality of life and
      personal well-being were negatively associated with the initial level of
      delinquent behavior, but positively associated with the growth rate of delinquent
      behavior. Regression analyses showed that family quality of life and personal
      well-being were related to the overall delinquent behavior concurrently at Wave
      4. However, Wave 1 family quality of life and personal well-being did not predict
      Wave 4 delinquent behavior with the initial level of delinquent behavior
      controlled. Lastly, we discussed the role of economic disadvantage and family non
      intactness as risk factors and family functioning and positive youth development
      as protective well-being factors in the development of adolescent well-being
      indexed by delinquent behavior.

PMID- 27881894
TI  - Competition-related factors directly influence preferences for facial cues of
      dominance in allies.
AB  - ABSTRACT: Alliance formation is a critical dimension of social intelligence in
      political, social and biological systems. As some allies may provide greater
      "leverage" than others during social conflict, the cognitive architecture that
      supports alliance formation in humans may be shaped by recent experience, for
      example in light of the outcomes of violent or non-violent forms intrasexual
      competition. Here we used experimental priming techniques to explore this issue.
      Consistent with our predictions, while men's preferences for dominant allies
      strengthened following losses (compared to victories) in violent intrasexual
      contests, women's preferences for dominant allies weakened following losses
      (compared to victories) in violent intrasexual contests. Our findings suggest
      that while men may prefer dominant (i.e. masculine) allies following losses in
      violent confrontation in order to facilitate successful resource competition,
      women may "tend and befriend" following this scenario and seek support from
      prosocial (i.e. feminine) allies and/or avoid the potential costs of dominant
      allies as long-term social partners. Moreover, they demonstrate facultative
      responses to signals related to dominance in allies, which may shape sex
      differences in sociality in light of recent experience and suggest that
      intrasexual selection has shaped social intelligence in humans. SIGNIFICANCE
      STATEMENT: Although alliance formation is an important facet of social
      intelligence in political and biological systems, we know relatively little about
      the cognitive processes involved in social preferences for allies. As recent
      experience may alter the leverage provided by different social partners, here we
      tested whether preferences for facial cues to dominance-prosociality (masculinity
      femininity) alter in light of recent experience of violent and economic contests
      for status. Our findings demonstrate sex-specific responses to these facial cues.
      While men's preferences for facial cues related to dominance in allies strengthen
      following losses (compared to wins) in violent contests, women's preferences for
      facial cues related to dominance in allies weaken following losses (compared to
      wins) in violent contests. These findings suggest that intrasexual selection, in
      part, has shaped the evolution of social intelligence in humans as revealed in
      flexibility in social preferences for allies.

PMID- 27881896
TI  - Dynamic habitat corridors for marine predators; intensive use of a coastal
      channel by harbour seals is modulated by tidal currents.
AB  - ABSTRACT: Previous studies have found that predators utilise habitat corridors to
      ambush prey moving through them. In the marine environment, coastal channels
      effectively act as habitat corridors for prey movements, and sightings of
      predators in such areas suggest that they may target these for foraging. Unlike
      terrestrial systems where the underlying habitat structure is generally static,
      corridors in marine systems are in episodic flux due to water movements created
      by tidal processes. Although these hydrographic features can be highly complex,
      there is generally a predictable underlying cyclic tidal pattern to their
      structure. For marine predators that must find prey that is often patchy and
      widely distributed, the underlying temporal predictability in potential foraging
      opportunities in marine corridors may be important drivers in their use. Here, we
      used data from land-based sightings and 19 harbour seals (Phoca vitulina) tagged
      with high-resolution GPS telemetry to investigate the spatial and temporal
      distribution patterns of seals in a narrow tidal channel. These seals showed a
      striking pattern in their distribution; all seals spent a high proportion of
      their time around the narrowest point of the channel. There was also a
      distinctive tidal pattern in the use of the channel; sightings of seals in the
      water peaked during the flood tide and were at a minimum during the ebb tide.
      This pattern is likely to be related to prey availability and/or foraging
      efficiency driven by the underlying tidal pattern in the water movements through
      the channel. SIGNIFICANCE STATEMENT: To maximise foraging efficiency, predators
      often make use of narrow constrictions in habitat to intercept prey using these
      corridors for movement. In the marine environment, narrow channels may act as
      corridors, and sightings of predators suggest that they may target these for
      foraging. Despite this, there is little information on how individual predators
      use such areas. Here, we investigate how individual harbour seals use a narrow
      coastal channel subject to strong tidal currents; results showed that seals spent
      the majority of their time at the narrowest point of the channel foraging during
      peak tidal currents. This highlights the importance of narrow channels for marine
      predators and suggests that this usually wide-ranging predator may restrict its
      geographic range to forage in the channel as a result of increased prey
      availability and/or foraging efficiency driven by water movements through the
      narrow corridor.

PMID- 27881895
TI  - State-dependent behavior and alternative behavioral strategies in brown trout
      (Salmo trutta L.) fry.
AB  - ABSTRACT: Animals generally adjust their behavior in response to bodily state
      (e.g., size and energy reserves) to optimize energy intake in relation to
      mortality risk, weighing predation probability against the risk of starvation.
      Here, we investigated whether brown trout Salmo trutta adjust their behavior in
      relation to energetic status and body size during a major early-life selection
      bottleneck, when fast growth is important. Over two consecutive time periods (P1
      and P2; 12 and 23 days, respectively), food availability was manipulated, using
      four different combinations of high (H) and low (L) rations (i.e., HH, HL, LH,
      and LL; first and second letter denoting ration during P1 and P2, respectively).
      Social effects were excluded through individual isolation. Following the
      treatment periods, fish in the HL treatment were on average 15-21 % more active
      than the other groups in a forced open-field test, but large within-treatment
      variation provided only weak statistical support for this effect. Furthermore,
      fish on L-ration during P2 tended to be more actively aggressive towards their
      mirror image than fish on H-ration. Body size was related to behavioral
      expression, with larger fish being more active and aggressive. Swimming activity
      and active aggression were positively correlated, forming a behavioral syndrome
      in the studied population. Based on these behavioral traits, we could also
      distinguish two behavioral clusters: one consisting of more active and aggressive
      individuals and the other consisting of less active and aggressive individuals.
      This indicates that brown trout fry adopt distinct behavioral strategies early in
      life. SIGNIFICANCE STATEMENT: This paper provides information on the state
      dependence of behavior in animals, in particular young brown trout. On the one
      hand, our data suggest a weak energetic state feedback where activity and
      aggression is increased as a response to short term food restriction. This
      suggests a limited scope for behavioral alterations in the face of starvation. On
      the other hand, body size is linked to higher activity and aggression, likely as
      a positive feedback between size and dominance. The experiment was carried out
      during the main population survival bottleneck, and the results indicate that
      growth is important during this stage, as 1) behavioral compensation to increase
      growth is limited, and 2) growth likely increases the competitive ability.
      However, our data also suggests that the population separates into two clusters,
      based on combined scores of activity and aggression (which are positively linked
      within individuals). Thus, apart from an active and aggressive strategy, there
      seems to be another more passive behavioral strategy.

PMID- 27881897
TI  - Elevated reproduction does not affect telomere dynamics and oxidative stress.
AB  - ABSTRACT: Oxidative stress and telomere dynamics are considered to be powerful
      biomarkers quantifying a potential trade-off between current reproduction and
      self-maintenance. Recent studies confirmed the negative impact of elevated
      reproduction on telomeres, but the evidence for the cost of reproduction in terms
      of oxidative stress remains equivocal. In order to induce reproductive costs, we
      experimentally manipulated reproductive effort by increasing brood size in
      captive zebra finches (Taeniopygia guttata) and additionally challenged all birds
      by a low ambient temperature to facilitate detection of these costs. We were not
      able to show any negative effects of elevated reproductive effort on telomere
      dynamics and oxidative stress among parents, although brood enlargement was
      effective in terms of total mass and number of fledged young. Interestingly,
      irrespective of brood size treatment, we found a significant increase in
      antioxidant capacity at peak breeding while oxidative damage did not change with
      time. Our results may suggest that reproduction, instead of generating costs, may
      stimulate physiological functions promoting self-maintenance in terms of higher
      protection against free radicals. Possibly, opportunistic breeders such as zebra
      finches may not impede their future performance for the sake of current
      reproduction. SIGNIFICANCE STATEMENT: This study interrogates a molecular
      background behind one of the most intriguing trade-offs that potentially occurs
      between self-maintenance and reproduction. We manipulated breeding effort in
      zebra finches to understand if the cost of reproduction can be mediated by
      telomere dynamics and oxidative stress. In our study system, we did not detect
      the direct reproductive costs in terms of parental oxidative damage and telomere
      loss; instead, these costs were paid by the offspring in terms of their inhibited
      growth rate. Moreover, we found that entering into the reproductive state
      strongly stimulated self-maintenance by increasing antioxidant capacity in
      parents. Our results emphasize that current reproductive success is not always
      prioritized over investment in body maintenance preventing the oxidative cost of
      reproduction.

PMID- 27881898
TI  - Chromosomal Localization and Contribution of Three Homoeologous Genes to
      Biosynthesis of Cytosolic Aspartate Aminotransferase in Common Wheat.
AB  - Chromosomal localization of the three homoeologous genes encoding cytosolic
      aspartate aminotransferase in common wheat (Triticum aestivum cv. Chinese Spring,
      2n = 6x = 42, AABBDD) was specified to: 3AL (0.42/0.61), 3BL (0.38/0.41) and 3DL
      (0.23/0.81) by a comparative zymographic analysis of the enzymatic activities in
      deletion lines. It was also attempted to precisely explain the nature of the
      relationship between a number of genes encoding alpha and beta subunits and a
      distribution of staining intensity of cytosolic aspartate aminotransferase
      allozyme activity bands using aneuploid lines of common wheat with modified third
      pair of homoeologous chromosomes from genomes A, B and D, on which the genes
      encoding subunit alpha (genome A) and beta (genome B and D) are localized. The
      highest consistency between the experimental results and the theoretical
      distributions was achieved by substituting values of alpha = 0.57 and beta = 0.43
      in a theoretical model. These results demonstrate that the individual
      participation of the diploid genome A in the biosynthesis of the cytosolic
      aspartate aminotransferase allozymes subunits is greater than the individual
      participation of the diploid genomes B and D.

PMID- 27881900
TI  - Organizational Conspiracy Beliefs: Implications for Leadership Styles and
      Employee Outcomes.
AB  - PURPOSE: Belief in conspiracy theories about societal events is widespread among
      citizens. The extent to which conspiracy beliefs about managers and supervisors
      matter in the micro-level setting of organizations has not yet been examined,
      however. We investigated if leadership styles predict conspiracy beliefs among
      employees in the context of organizations. Furthermore, we examined if such
      organizational conspiracy beliefs have implications for organizational commitment
      and turnover intentions. DESIGN/METHODOLOGY/APPROACH: We conducted a survey among
      a random sample of the US working population (N = 193). FINDINGS: Despotic,
      laissez-faire, and participative leadership styles predicted organizational
      conspiracy beliefs, and the relations of despotic and laissez-faire leadership
      with conspiracy beliefs were mediated by feelings of job insecurity. Furthermore,
      organizational conspiracy beliefs predicted, via decreased organizational
      commitment, increased turnover intentions. IMPLICATIONS: Organizational
      conspiracy beliefs matter for how employees perceive their leaders, how they feel
      about their organization, and whether or not they plan to quit their jobs. A
      practical implication, therefore, is that it would be a mistake for managers to
      dismiss organizational conspiracy beliefs as innocent rumors that are harmless to
      the organization. ORIGINALITY/VALUE: Three novel conclusions emerge from this
      study. First, organizational conspiracy beliefs occur frequently among employees.
      Second, participative leadership predicts decreased organizational conspiracy
      beliefs; despotic and laissez-faire leadership predict increased organizational
      conspiracy beliefs due to the contribution of these destructive leadership styles
      to an insecure work environment. Third, organizational conspiracy beliefs harm
      organizations by influencing employee commitment and, indirectly, turnover
      intentions.

PMID- 27881901
TI  - Applicant Personality and Procedural Justice Perceptions of Group Selection
      Interviews.
AB  - PURPOSE: We investigated how job applicants' personalities influence perceptions
      of the structural and social procedural justice of group selection interviews
      (i.e., a group of several applicants being evaluated simultaneously). We
      especially addressed trait interactions between neuroticism and extraversion (the
      affective plane) and extraversion and agreeableness (the interpersonal plane).
      DESIGN/METHODOLOGY/APPROACH: Data on personality (pre-interview) and justice
      perceptions (post-interview) were collected in a field study among job applicants
      (N = 97) attending group selection interviews for positions as teachers in a
      Norwegian high school. FINDINGS: Interaction effects in hierarchical regression
      analyses showed that perceptions of social and structural justice increased with
      levels of extraversion among high scorers on neuroticism. Among emotionally
      stable applicants, however, being introverted or extraverted did not matter to
      justice perceptions. Extraversion did not impact on the perception of social
      justice for applicants low in agreeableness. Agreeable applicants, however,
      experienced the group interview as more socially fair when they were also
      extraverted. IMPLICATIONS: The impact of applicant personality on justice
      perceptions may be underestimated if traits interactions are not considered.
      Procedural fairness ratings for the group selection interview were high, contrary
      to the negative reactions predicted by other researchers. There was no indication
      that applicants with desirable traits (i.e., traits predictive of job
      performance) reacted negatively to this selection tool. ORIGINALITY/VALUE:
      Despite the widespread use of interviews in selection, previous studies of
      applicant personality and fairness reactions have not included interviews. The
      study demonstrates the importance of previously ignored trait interactions in
      understanding applicant reactions.

PMID- 27881899
TI  - The Comparatively Proteomic Analysis in Response to Cold Stress in Cassava
      Plantlets.
AB  - Cassava (Manihot esculenta Crantz) is a tropical root crop and sensitive to low
      temperature. However, it is poorly to know how cassava can modify its metabolism
      and growth to adapt to cold stress. An investigation aimed at a better
      understanding of cold-tolerant mechanism of cassava plantlets was carried out
      with the approaches of physiology and proteomics in the present study. The
      principal component analysis of seven physiological characteristics showed that
      electrolyte leakage (EL), chlorophyll content, and malondialdehyde (MDA) may be
      the most important physiological indexes for determining cold-resistant abilities
      of cassava. The genome-wide proteomic analysis showed that 20 differential
      proteins had the same patterns in the apical expanded leaves of cassava SC8 and
      Col1046. They were mainly related to photosynthesis, carbon metabolism and energy
      metabolism, defense, protein synthesis, amino acid metabolism, signal
      transduction, structure, detoxifying and antioxidant, chaperones, and DNA-binding
      proteins, in which 40 % were related with photosynthesis. The remarkable
      variation in photosynthetic activity and expression level of peroxiredoxin is
      closely linked with expression levels of proteomic profiles. Moreover, analysis
      of differentially expressed proteins under cold stress is an important step
      toward further elucidation of mechanisms of cold stress resistance.

PMID- 27881902
TI  - Temperature-Dependent Oxygen Effect on NMR D-[Formula: see text] Relaxation
      Diffusion Correlation of n-Alkanes.
AB  - Nuclear magnetic resonance (NMR) diffusion-relaxation correlation experiments (D
      [Formula: see text]) are widely used for the petrophysical characterisation of
      rocks saturated with petroleum fluids both in situ and for laboratory analyses.
      The encoding for both diffusion and relaxation offers increased fluid typing
      contrast by discriminating fluids based on their self-diffusion coefficients,
      while relaxation times provide information about the interaction of solid and
      fluid phases and associated confinement geometry (if NMR responses of pure fluids
      at particular temperature and pressure are known). Petrophysical interpretation
      of D-[Formula: see text] correlation maps is typically assisted by the "standard
      alkane line"-a relaxation-diffusion correlation valid for pure normal alkanes and
      their mixtures in the absence of restrictions to diffusing molecules and effects
      of internal gradients. This correlation assumes fluids are free from paramagnetic
      impurities. In situations where fluid samples cannot be maintained at air-free
      state the diffusion-relaxation response of fluids shift towards shorter
      relaxation times due to oxygen paramagnetic relaxation enhancement.
      Interpretation of such a response using the "standard alkane line" would be
      erroneous and is further complicated by the temperature-dependence of oxygen
      solubility for each component of the alkane mixture. We propose a diffusion
      relaxation correlation suitable for interpretation of low-field NMR D-[Formula:
      see text] responses of normal alkanes and their mixtures saturating rocks over a
      broad temperature range, in equilibrium with atmospheric air. We review and where
      necessary revise existing viscosity-relaxation correlations. Findings are applied
      to diffusion-relaxation dependencies taking into account the temperature
      dependence of oxygen solubility and solvent vapour pressure. The effect is
      demonstrated on a partially saturated carbonate rock.

PMID- 27881903
TI  - Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in
      3T3-L1 Adipocytes through an Inhibition of NFkappaB.
AB  - In an obese state, Toll-like receptor-4 (TLR-4) upregulates proinflammatory
      adipokines secretion including monocyte chemotactic protein-1 (MCP-1) in adipose
      tissue. In contrast, G-protein coupled receptor 120 (GPR120) mediates antiobesity
      effects. The aim of this study was to determine the signaling pathway by which
      Forskolin (FK), a cyclic adenosine monophosphate- (cAMP-) promoting agent causing
      positive changes in body composition in overweight and obese adult men, affects
      MCP-1 and GPR120 expression during an inflammatory response induced by
      lipopolysaccharide (LPS) in adipocytes, such as in an obese state. 3T3-L1 cells
      differentiated into adipocytes (DC) were stimulated with LPS in the absence or
      presence of FK and inhibitors of TLR-4 and inhibitor of kappa B (IkappaBalpha).
      In DC, LPS increased MCP-1, TLR-4, and nuclear factor-kappaB1 (NFkappaB1) mRNA
      levels, whereas it decreased GPR120 mRNA levels. In DC, FK inhibited the LPS
      induced increase in MCP-1, TLR-4, and NFkappaB1 mRNA levels and the LPS-induced
      decrease in GPR120 mRNA. BAY11-7082 and CLI-095 abolished these LPS-induced
      effects. In conclusion, FK inhibits LPS-induced increase in MCP-1 mRNA levels and
      decrease in GPR120 mRNA levels in adipocytes and may be a potential treatment for
      inflammation in obesity. Furthermore, TLR-4-induced activation of NFkappaB may be
      involved in the LPS-induced regulation of these genes.

PMID- 27881905
TI  - Qualitative longitudinal analysis of symptoms in patients with primary and
      metastatic brain tumours.
AB  - Primary and metastatic brain tumour patients are treated with surgery, radiation
      therapy and chemotherapy. Such treatments often result in short- and long-term
      symptoms that impact cognitive, emotional and physical function. Therefore,
      understanding the transition of symptom burden over time is important for guiding
      treatment and follow-up of brain tumour patients with symptom-specific
      interventions. We describe the use of a hidden Markov model with person-specific
      random effects for the temporal pattern of symptom burden. Clinically relevant
      covariates are also incorporated in the analysis through the use of generalized
      linear models.

PMID- 27881904
TI  - Long Noncoding RNAs in Metabolic Syndrome Related Disorders.
AB  - Ribonucleic acids (RNAs) are very complex and their all functions have yet to be
      fully clarified. Noncoding genes (noncoding RNA, sequences, and pseudogenes)
      comprise 67% of all genes and they are represented by housekeeping noncoding RNAs
      (transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), and small
      nucleolar RNA (snoRNA)) that are engaged in basic cellular processes and by
      regulatory noncoding RNA (short and long noncoding RNA (ncRNA)) that are
      important for gene expression/transcript stability. In this review, we summarize
      data concerning the significance of long noncoding RNAs (lncRNAs) in metabolic
      syndrome related disorders, focusing on adipose tissue and pancreatic islands.

PMID- 27881906
TI  - Genetic and immunohistochemical analysis of HSPA5 in mouse and human retinas.
AB  - PURPOSE: Photoreceptor degenerative diseases are among the leading causes of
      vision loss. Although the causative genetic mutations are often known, mechanisms
      leading to photoreceptor degeneration remain poorly defined. We have previously
      demonstrated that the photoreceptor membrane-associated protein XAP-1 antigen is
      a product of the HSPA5 gene. In this study, we used systems genetic methods,
      statistical modeling, and immunostaining to identify and analyze candidate genes
      that modulate Hspa5 expression in the retina. METHODS: Quantitative trait locus
      (QTL) mapping was used to map the genomic region that regulates Hspa5 in the
      cross between C57BL/6J X DBA/2J mice (BXD) genetic reference panel. The stepwise
      refinement of candidate genes was based on expression QTL mapping, gene
      expression correlation analyses (direct and partial), and analysis of regional
      sequence variants. The subcellular localization of candidate proteins and HSPA5
      in mouse and human retinas was evaluated by immunohistochemistry. Differences in
      the localization of extracellular HSPA5 were assessed between healthy human donor
      and atrophic age-related macular degeneration (AMD) donor eyes. RESULTS: In the
      eyes of healthy mice, extracellular HSPA5 was confined to the area around the
      cone photoreceptor outer segments. Mapping variation in Hspa5 mRNA expression
      levels in the retina revealed a statistically significant trans-acting expression
      QTL (eQTL) on Chromosome 2 (Chr 2) and a suggestive locus on Chr 15. Sulf2 on Chr
      2 was the strongest candidate gene based on partial correlation analysis, Pearson
      correlation with Hspa5, expression levels in the retina, a missense variant in
      exon 14, and its reported function in the extracellular matrix and
      interphotoreceptor matrix. SULF2 is localized to the rod and cone photoreceptors
      in both human and mouse retinas. In human retinas with no pathology,
      extracellular HSPA5 was localized around many cones within the macular area. In
      contrast, fewer HSPA5-immunopositive cones were observed in the retinas from AMD
      donors. CONCLUSIONS: We identified Sulf2 as a candidate gene modulating the Hspa5
      expression in the retina. The preferential loss of HSPA5 in the
      interphotoreceptor matrix around cone photoreceptors in atrophic AMD retinas
      opens up new avenues for exploring the changes in interphotoreceptor matrix (IPM)
      that are associated with macular disease.

PMID- 27881908
TI  - Functional study of two biochemically unusual mutations in GUCY2D Leber
      congenital amaurosis expressed via adenoassociated virus vector in mouse retinas.
AB  - PURPOSE: To test, in living photoreceptors, two mutations, S248W and R1091x, in
      the GUCY2D gene linked to Leber congenital amaurosis 1 (LCA1) that fail to
      inactivate the catalytic activity of a heterologously expressed retinal membrane
      guanylyl cyclase 1 (RetGC1). METHODS: GUC2YD cDNA constructs coding for wild-type
      human (hWT), R1091x, and S248W GUCY2D under the control of the human rhodopsin
      kinase promoter were expressed in Gucy2e-/-Gucy2f-/- knockout (GCdKO) mouse
      retinas, which lack endogenous RetGC activity. The constructs were delivered via
      subretinally injected adenoassociated virus (AAV) vector in one eye, leaving the
      opposite eye as the non-injected negative control. After testing with
      electroretinography (ERG), the retinas extracted from the AAV-treated and control
      eyes were used in guanylyl cyclase activity assays, immunoblotting, and anti
      RetGC1 immunofluorescence staining. RESULTS: Cyclase activity in retinas treated
      with either hWT or R1091x GUCY2D transgenes was similar but was undetectable in
      the S248W GUCY2D-treated retinas, which starkly contrasts their relative
      activities when heterologously expressed in human embryonic kidney (HEK293)
      cells. Rod and cone ERGs, absent in GCdKO, appeared in the hWT and R1091x GUCY2D
      injected eyes, while the S248W mutant failed to restore scotopic ERG response and
      enabled only rudimentary photopic ERG response. The hWT and R1091x GUCY2D
      immunofluorescence was robust in the rod and cone outer segments, whereas the
      S248W was detectable only in the sparse cone outer segments and sporadic
      photoreceptor cell bodies. Robust RetGC1 expression was detected with
      immunoblotting in the hWT and R1091x-treated retinas but was marginal at best in
      the S248W GUCY2D retinas, despite the confirmed presence of the S248W GUCY2D
      transcripts. CONCLUSIONS: The phenotype of S248W GUCY2D in living retinas did not
      correlate with the previously described normal biochemical activity of this
      mutant when heterologously expressed in non-photoreceptor cell culture. This
      result suggests that the S248W mutation contributes to LCA1 by hampering the
      expression, processing, and/or cellular transport of GUCY2D, rather than its
      enzymatic properties. In contrast, the effective restoration of rod and cone
      function by R1091x GUCY2D is paradoxical and does not explain the severe loss of
      vision typical for LCA1 associated with that mutant allele.

PMID- 27881909
TI  - Comparison of choroidal thickness measurements between spectral-domain OCT and
      swept-source OCT in normal and diseased eyes.
AB  - PURPOSE: Sub-foveal choroidal thickness (SFCT) is affected in many ocular
      diseases. The aim of this study was to compare SFCT measurements between Topcon
      3D 2000 spectral-domain optical coherence tomography (SD-OCT) and Topcon swept
      source OCT (SS-OCT), with different laser wavelengths, in normal and diseased
      populations. MATERIALS AND METHODS: This was a prospective, cross-sectional,
      noninterventional study including 27 normal volunteers and 27 participants with
      retinal disease. OCT scans were performed sequentially and under standardized
      conditions using both SD-OCT and SS-OCT. The OCT scans were evaluated by two
      independent graders. Paired t-tests and intraclass correlation coefficients
      (ICCs) were used to assess the statistically significant difference between SFCT
      measurements as measured by the two devices. RESULTS: Mean SFCT measurements for
      all 54 participants were 264.9+/-103.1 MUm using SD-OCT (range: 47-470 MUm) and
      278.5+/-110.5 MUm using SS-OCT (range: 56-502 MUm), with an inter-device ICC of
      0.850. Greater variability was noted in the diseased eyes. Inter-device ICCs were
      0.870 (95% CI; 0.760-0.924) and 0.840 (95% CI; 0.654-0.930) for normal and
      diseased eyes, respectively. However, the difference was not statistically
      significant (P=0.132). CONCLUSION: Both machines reliably measure SFCT. Larger
      studies are needed to confirm these findings.

PMID- 27881907
TI  - Retinal safety of intravitreal rtPA in healthy rats and under excitotoxic
      conditions.
AB  - PURPOSE: Intravitreal recombinant tissue plasminogen activator (rtPA) is used off
      label for the surgical management of submacular hemorrhage, a severe complication
      of neovascular age-related macular degeneration. rtPA is approved for coronary
      and cerebral thrombolysis. However, in ischemic stroke rtPA is known to increase
      excitotoxic neural cell death by interacting with the N-methyl-D-aspartate (NMDA)
      receptor. We therefore investigated the retinal toxicity of rtPA in healthy rats
      and in a model of NMDA-induced retinal excitotoxicity. METHODS: First, rtPA at
      three different doses (2.16 ug/5 ul, 0.54 ug/5 ul, and 0.27 ug/5 ul) or vehicle
      (NaCl 0.9%) was injected intravitreally in healthy rat eyes. Electroretinograms
      (ERGs) were performed at 24 h or 7 days. Annexin V-fluorescein isothiocyanate
      (FITC)-labeled apoptotic retinal ganglion cells (RGCs) were counted on
      flatmounted retinas at 24 h or 7 days. Next, NMDA + vehicle or NMDA + rtPA (0.27
      ug/5 ul) was injected intravitreally to generate excitotoxic conditions.
      Apoptotic annexin V-FITC-labeled RGCs and surviving Brn3a-labeled RGCs were
      quantified on flatmounted retinas and radial sections, 18 h after treatment.
      RESULTS: In healthy rat eyes, the number of apoptotic RGCs was statistically
      significantly increased 24 h after the administration of rtPA at the highest dose
      (2.16 ug/5 ul; p = 0.0250) but not at the lower doses of 0.54 and 0.27 ug/5 ul (p
      = 0.36 and p = 0.20), compared to vehicle. At day 7, there was no difference in
      the apoptotic RGC count between the rtPA- and vehicle-injected eyes (p = 0.70, p
      = 0.52, p = 0.11). ERG amplitudes and implicit times were not modified at 24 h or
      7 days after injection of any tested rtPA doses, compared to the baseline.
      Intravitreal administration of NMDA induced RGC death, but under these
      excitotoxic conditions, coadministration of rtPA did not increase the number of
      dead RGCs (p = 0.70). Similarly, the number of surviving RGCs on the flatmounted
      retinas and retinal sections did not differ between the eyes injected with NMDA +
      vehicle and NMDA + rtPA (p = 0.59 and p = 0.67). CONCLUSIONS: At low clinical
      equivalent doses corresponding to 25 ug/0.1 ml in humans, intravitreal rtPA is
      not toxic for healthy rat retinas and does not enhance NMDA-induced
      excitotoxicity. Vitreal equivalent doses >=200 ug/0.1 ml should be avoided in
      patients, due to potential RGC toxicity.

PMID- 27881910
TI  - Low-dose modified-release prednisone in axial spondyloarthritis: 3-month efficacy
      and tolerability.
AB  - BACKGROUND: Oral glucocorticoids (GCs) have been shown to be effective in
      reducing the inflammatory symptoms of rheumatoid arthritis, but their use is not
      supported by evidence in spondyloarthritis (SpA). Modified-release (MR) oral
      prednisone taken at bedtime has been shown to be more effective than immediate
      release prednisone taken in the morning. The efficacy of low-dose MR prednisolone
      in patients with SpA is unknown. PATIENTS AND METHODS: This single-center cohort
      study retrospectively assessed the effectiveness and safety of 12-week low-dose
      MR prednisone (5 mg daily, bedtime administration) in GC-naive adult patients
      with symptomatic axial SpA. A 50% improvement of the Bath Ankylosing Spondylitis
      Disease Activity Index (BASDAI) or a final BASDAI score of <4 according to
      disease activity at baseline was chosen as the primary outcome parameter after MR
      prednisone. RESULTS: Fifty-seven patients were evaluated; of them, 41 had an
      active disease (BASDAI score of >=4) at baseline. MR prednisone significantly
      reduced BASDAI (from 5.5+/-2.6 to 3.0+/-2.8, P<0.001) as well as inflammatory
      symptoms, pain, fatigue and morning stiffness. The overall response rate after MR
      prednisone was 52.6% (53.7% in patients with active SpA and 50.0% in patients
      with low-active disease; nonsignificant). At multivariable analysis, none of the
      considered clinical findings independently predicted the response to MR
      prednisone in subjects with active SpA. Overall, seven patients (11.8%) had
      nonserious adverse drug reactions after MR prednisone. CONCLUSION: In patients
      with symptomatic SpA and naive to GCs, low-dose MR prednisone reduced the
      symptoms and clinical indexes of disease activity and showed a positive safety
      profile.

PMID- 27881911
TI  - Systematic review and meta-analysis of randomized controlled trials on Wenxin
      keli.
AB  - OBJECTIVE: The aim of the study was to evaluate the effectiveness, safety, and
      cost associated with Wenxin keli in the treatment of cardiovascular diseases
      based on meta-analysis. METHODS: The terms "Wenxin keli" and "Wenxin" were used
      as the search terms in the PubMed, ProQuest, Springer, the Cochrane Library, CNKI
      (China National Knowledge Infrastructure), VIP (Chinese Scientific Journals
      Database), and Wan fang electronic databases (from January 2000 to October 2015).
      Relevant print journals and conference papers were also searched. Studies on
      randomized controlled trials (RCTs) of Wenxin keli used in the treatment of
      cardiovascular diseases were screened, and its indications were classified. Meta
      analysis of these studies was conducted using the RevMan 5.2 software. RESULTS: A
      total of 49 RCTs (n=4,610) were included, 29 of which focused on arrhythmia,
      seven on angina, seven on heart failure, two on viral myocarditis, and four on
      menopausal syndrome. Analysis of the therapeutic indications of Wenxin keli
      showed that it was comparatively more curative and effective than other available
      treatments for cardiovascular diseases. CONCLUSION: Wenxin keli showed better
      clinical efficacy in the treatment of arrhythmia, angina, and heart failure;
      however, more high-quality evidence is needed to support its use in the clinical
      setting.

PMID- 27881913
TI  - Effectiveness of the Vital Aging program to promote active aging in Mexican older
      adults.
AB  - INTRODUCTION: Aging is not only a population phenomenon but also an experience
      and an individual reality. Vital Aging(r) is a program that considers active
      aging as the lifelong adaptation process of maximizing health and independence,
      physical and cognitive functioning, positive affect regulation and control, and
      social engagement. Through its different versions and editions, it has
      demonstrated being an effective program to promote active aging. The aim of this
      study is to determine the effectiveness of the "face-to-face" and "combined"
      versions of the program to promote active aging in Mexican older adults trial.
      METHODS: Seventy-six older adults aged 60 years and over participated in a quasi
      experimental study and were recruited in a senior center to participate in the
      two experimental conditions: Vital Aging face-to-face (VA-FF) (n=35) and Vital
      Aging combined (VA-C; multimedia/face-to-face) (n=15), and the remaining 26
      adults were assigned to a control group. Pretest and posttest assessments were
      performed after the theoretical-practical intervention. Mean differences and size
      effects were calculated for estimating the effect of the program. RESULTS: At the
      end of the study, participants showed improvements in the active aging outcome
      measures. Positive effects were observed in the frequency of intellectual,
      cultural - artistic, and social activities, perceptions of aging, satisfaction
      with social relationships, and self-efficacy for aging. Additionally, those who
      participated in VA-FF showed better memory performance, meta-memory, and a trend
      to report less memory problems, while older persons in VA-C showed a trend to
      have better life satisfaction. No effects were observed in physical activity,
      frequency of social relationships, and subjective health. CONCLUSION: Findings
      show that the Vital Aging program in face-to-face and combined versions
      encourages active aging in Mexican older persons. These results are in general
      similar to those found in editions performed in Spain, revealing its consistency
      as a cross-cultural practical initiative for promoting active aging.

PMID- 27881912
TI  - Assessing the feasibility and quality of shared decision making in China:
      evaluating a clinical encounter intervention for Chinese patients.
AB  - BACKGROUND: The aim of this study was to evaluate the feasibility of using the
      Statin Choice decision aid to have discussions about starting a statin medication
      for cardiovascular risk reduction in Chinese patients with stable coronary artery
      diseases. METHODS: A prospective, pilot study of the Statin Choice decision aid
      in two teaching hospitals in Northern China was conducted. A total of seven
      clinicians were enrolled and underwent a 12-hour, group-based, in-person training
      on shared decision making (SDM) and the Statin Choice decision aid. Then, these
      clinicians used the Statin Choice decision aid in patients during a clinical
      encounter. A total of 86 patients aged 40-80 years, who had stable angina, were
      enrolled. All clinical encounters were video recorded. A team of three
      researchers viewed and scored all the encounter recordings to evaluate the SDM
      process and fidelity to the intervention using the OPTION scale and Fidelity
      scale, respectively. All the patients were followed up for 12 months to record
      adherence to statin and any major adverse cardiac events (MACEs). RESULTS: The
      average scores on the OPTION normalized score and Fidelity scale were 21 (range,
      3-32; out of a possible, 48) and 10 (range, 6-10; out of a possible, 10),
      respectively. This suggested that Chinese clinicians who were using Statin Choice
      in their patients were able to exhibit behaviors consistent with SDM at a level
      that is similar to that reported in Western countries. After SDM, the statin
      adherence was 94.5% (69/73), and the proportion of MACEs was 2.9% (2/69).
      CONCLUSION: Using an encounter decision aid developed in the US, it was feasible
      to implement SDM in a referral cardiology practice in Mainland China. Further
      work to ensure that the encounter aid is pertinent to the Chinese population and
      that SDM is tested in at-risk patients could contribute to the implementation of
      SDM across Mainland China.

PMID- 27881914
TI  - Habitual cocoa intake reduces arterial stiffness in postmenopausal women
      regardless of intake frequency: a randomized parallel-group study.
AB  - Arterial stiffness is substantially higher in postmenopausal than in
      premenopausal women. Daily cocoa intake has been shown to reduce central arterial
      stiffness in health adults, regardless of age; however, the effect of cocoa
      intake frequency on arterial stiffness in postmenopausal women remains unclear.
      Therefore, the purpose of this study was to investigate the effects of cocoa
      intake frequency on arterial stiffness in postmenopausal women. A total of 26
      postmenopausal women (mean age +/- standard deviation 64+/-12 years) were
      randomly assigned to two groups with different cocoa-intake frequencies: one
      group ingested 17 g of cocoa once daily except on Sundays (every-day group,
      n=13), and the other ingested 17 g of cocoa twice daily every other day (every
      other-day group, n=13). These intake regimens were maintained in both groups for
      12 weeks. Carotid-femoral pulse-wave velocity and femoral-ankle pulse-wave
      velocity were measured in both groups at baseline and again at the end of the 12
      week study period. Compared to baseline, both pulse-wave velocities had
      significantly decreased after the 12-week study period in both groups (P<0.05).
      However, no significant difference in degree of change was observed between the
      two groups. Although this study did not include a sedentary control group, these
      results suggest that regardless of frequency, habitual cocoa intake reduces
      central and peripheral arterial stiffness in postmenopausal women.

PMID- 27881915
TI  - COPD care delivery pathways in five European Union countries: mapping and health
      care professionals' perceptions.
AB  - BACKGROUND: COPD is among the leading causes of chronic morbidity and mortality
      in the European Union with an estimated annual economic burden of ?25.1 billion.
      Various care pathways for COPD exist across Europe leading to different responses
      to similar problems. Determining these differences and the similarities may
      improve health and the functioning of health services. OBJECTIVE: The aim of this
      study was to compare COPD patients' care pathway in five European Union countries
      including England, Ireland, the Netherlands, Greece, and Germany and to explore
      health care professionals' (HCPs) perceptions about the current pathways.
      METHODS: HCPs were interviewed in two stages using a qualitative, semistructured
      email interview and a face-to-face semistructured interview. RESULTS: Lack of
      communication among different health care providers managing COPD and
      comorbidities was a common feature of the studied care pathways. General
      practitioners/family doctors are responsible for liaising between different
      teams/services, except in Greece where this is done through pulmonologists.
      Ireland and the UK are the only countries with services for patients at home to
      shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited
      resources, and poor patient engagement as issues in the current pathways.
      Furthermore, no specified role exists for pharmacists and informal carers.
      CONCLUSION: Service and professional integration between care settings using a
      unified system targeting COPD and comorbidities is a priority. Better
      communication between health care providers, establishing a clear role for
      informal carers, and enhancing patients' engagement could optimize current care
      pathways resulting in a better integrated system.

PMID- 27881917
TI  - Preparation and characterization of novel chitosan-protamine nanoparticles for
      nucleus-targeted anticancer drug delivery.
AB  - It is well known that most anticancer drugs commonly show high toxicity to the
      DNA of tumor cells and exert effects by combining with the DNA or associated
      enzymes in the nucleus. Most developed drugs are first delivered into the
      cytoplasm and then transferred to the nucleus through the membrane pores.
      Sometimes, the transportation of drugs from cytoplasm to nucleus is not efficient
      and often results in poor therapeutic effects. In this study, we developed
      special and novel nanoparticles (NPs) made of chitosan and protamine for targeted
      nuclear capture of drugs to enhance anticancer effects. The anticancer effects of
      nuclear targeted-delivery of drugs in NPs were also evaluated by investigating
      cytotoxicity, cellular uptake mechanism, and cell apoptosis on cells. Chitosan
      protamine NPs were characterized by good drug entrapment, sustained release,
      small average particle size, low polydispersity index, and high encapsulation
      efficiency; and accomplished the efficient nuclear delivery of fluorouracil (5
      Fu). Compared with free 5-Fu and 5-Fu-loaded chitosan NPs, treatment of A549
      cells and HeLa cells with 5-Fu-loaded chitosan-protamine NPs showed the highest
      cytotoxicity and further induced the significant apoptosis of cells. In addition,
      5-Fu-loaded chitosan-protamine NPs exhibited the best efficiency in inhibiting
      tumor growth than the other three formulations. 5-Fu-loaded chitosan-protamine
      NPs enhanced antitumor efficacy through the targeted nuclear capture of drugs and
      showed promising potential as a nanodelivery system for quickly locating drugs in
      the nucleus of cells.

PMID- 27881916
TI  - Osseointegration of nanohydroxyapatite- or nano-calcium silicate-incorporated
      polyetheretherketone bioactive composites in vivo.
AB  - Polyetheretherketone (PEEK) exhibits appropriate biomechanical strength as well
      as good biocompatibility and stable chemical properties but lacks bioactivity and
      cannot achieve highly efficient osseointegration after implantation.
      Incorporating bioceramics into the PEEK matrix is a feasible approach for
      improving its bioactivity. In this study, nanohydroxyapatite (n-HA) and nano
      calcium silicate (n-CS) were separately incorporated into PEEK to prepare n
      HA/PEEK and n-CS/PEEK biocomposites, respectively, using a compounding and
      injection-molding technique, and the in vitro degradation characteristics were
      evaluated. Discs with a diameter of 8 mm were inserted in 8 mm full-thickness
      cranial defects in rabbits for 4 and 8 weeks, and implantation of pure PEEK was
      used as the control. Three-dimensional microcomputed tomography, histological
      analysis, fluorescence microscopy of new bone formation, and scanning electron
      microscopy were used to evaluate the osseointegration performance at the
      bone/implant interface. The results of the in vitro degradation study
      demonstrated that degradation of n-CS on the surface of n-CS/PEEK could release
      Ca and Si ions and form a porous structure. In vivo tests revealed that both n
      CS/PEEK and n-HA/PEEK promoted osseointegration at the bone/implant interface
      compared to PEEK, and n-CS/PEEK exhibited higher bone contact ratio and more new
      bone formation compared with those of n-HA/PEEK, implying that n-CS/PEEK
      possessed a stronger ability to promote osseointegration. These two PEEK
      biocomposites are promising materials for the preparation of orthopedic or
      craniofacial implants.

PMID- 27881918
TI  - Sex differences in the course of schizophrenia across diverse regions of the
      world.
AB  - This study explores sex differences in the outcomes of patients with
      schizophrenia (clinical/functional remission and recovery) across diverse regions
      of the world (Northern Europe, Southern Europe, Central and Eastern Europe, Latin
      America, East Asia, and North Africa and the Middle East). Data (n=16,380 for
      this post hoc analysis) were taken from the World-Schizophrenia Health Outcomes
      Study. In most regions, females had a later age at first service contact for
      schizophrenia, a lower level of overall/negative symptom severity, lower rates of
      alcohol/substance abuse and paid employment, and higher percentages of having a
      spouse/partner and independent living. Overall, females had slightly higher rates
      of clinical remission (58.0% vs 51.8%), functional remission (22.8% vs 16.0%),
      and recovery (16.5% vs 16.0%) at 36 months (P<0.001 for all). This pattern was
      consistently observed in Southern Europe and Northern Europe even after
      controlling for baseline sex differences, but not in other regions. In Central
      and Eastern Europe, rates of clinical remission were higher in females at 36
      months, but those of functional remission and recovery were similar between males
      and females. The opposite was observed for Latin America. In East Asia, sex
      differences were rarely observed for these outcomes. Finally, in North Africa and
      the Middle East, sex differences in these outcomes were pronounced only in
      regression analyses. These regional variations shed light on the importance of
      psychosocial and cultural factors and their effects on sex in the prognosis of
      schizophrenia.

PMID- 27881919
TI  - Posttraumatic stress and depression in Yazidi refugees.
AB  - AIM: The aim of this investigation was to determine the frequency of mental
      pathologies in children and adolescents of the Yazidi minority group who
      immigrated to Turkey from Iraq. The refugees were asked about preventive and risk
      factors that occurred before and after their immigration. SUBJECTS AND METHODS:
      The sample comprised 55 children and adolescents (30 males and 25 females) who
      were Yazidi refugees and had settled in the Uckuyular, Oguz, Onbasi, and Ugurca
      villages of Batman, Turkey. The study was conducted 9 months after the refugees
      had immigrated. The participants were evaluated in their native language through
      a semistructured interview titled "Reliability and Validity of Schedule for
      Affective Disorders and Schizophrenia for School-Age Children - Present and
      Lifetime Version - Turkish Version". A sociodemographic form was prepared so that
      investigators could understand their traumatic experiences before and after the
      migration and their current social conditions. All the interviews were conducted
      in the participants' native language without the help of translators. The
      investigators filled out the sociodemographic forms. RESULTS: Posttraumatic
      stress disorder (PTSD) was detected in 20 children (36.4%), depression in 18
      (32.7%), nocturnal enuresis in six (10.9%), and anxiety in four (7.3%). The
      following factors were found to be associated with depression: witnessing
      violence and/or death, being a girl, having older parents, being the elder child,
      and having multiple siblings (P<0.05). Risk factors for PTSD, depression, and
      comorbid conditions included witnessing violence and/or death (P<0.05). Four
      participants were observed to have both PTSD and depression (7.3%). CONCLUSION:
      Most of the refugee children had experienced serious traumatic events in their
      home country. PTSD, depression, and comorbid mental problems are frequently seen
      in refugee children.

PMID- 27881921
TI  - The occurrence and predictive factors of sleep paralysis in university students.
AB  - The aim of the present study was to assess the occurrence and predictive factors
      of sleep paralysis (SP) in Czech university students. Our sample included 606
      students who had experienced at least one episode of SP. The participants
      completed an online battery of questionnaires involving questionnaires focused on
      describing their sleep habits and SP episodes, the 18-item Boundary Questionnaire
      (BQ-18), the Modified Tellegen Absorption Scale (MODTAS), the Dissociative
      Experience Scale Taxon, the Beck Depression Inventory II and the State-Trait
      Anxiety Inventory. The strongest predictive factor for the frequency of SP
      episodes was nightmares. The strongest predictive factor for the intensity of
      fear was dream occurrences. In our study sample, SP was more common in women than
      in men. Those who scored higher in BQ-18 experienced more often pleasant episodes
      of SP and those who scored higher in MODTAS were more likely to experience SP
      accompanied with hallucinations. While 62% of respondents answered that their SP
      was accompanied by intense fear, 16% reported that they experienced pleasant
      feelings during SP episodes. We suggest that not only the known rapid eye
      movement sleep dysregulation but also some personality variables may contribute
      to the characteristics of SP.

PMID- 27881920
TI  - Altered spontaneous brain activity pattern in patients with high myopia using
      amplitude of low-frequency fluctuation: a resting-state fMRI study.
AB  - OBJECTIVE: Many previous reports have demonstrated significant neural anatomy
      changes in the brain of high myopic (HM) patients, whereas the spontaneous brain
      activity changes in the HM patients at rest are not well studied. Our objective
      was to use amplitude of low-frequency fluctuation (ALFF) method to investigate
      the changes in spontaneous brain activity in HM patients and their relationships
      with clinical features. METHODS: A total of 38 patients with HM (17 males and 21
      females) and 38 healthy controls (HCs) (17 males and 21 females) closely matched
      in age, sex, and education underwent resting-state functional magnetic resonance
      imaging scans. The ALFF method was used to assess local features of spontaneous
      brain activity. The relationship between the mean ALFF signal values in many
      brain regions and the clinical features in HM patients was calculated by
      correlation analysis. RESULTS: Compared with HCs, the HM patients had
      significantly lower ALFF in the right inferior and middle temporal gyrus, left
      middle temporal gyrus, left inferior frontal gyrus/putamen, right inferior
      frontal gyrus/putamen/insula, right middle frontal gyrus, and right inferior
      parietal lobule and higher ALFF values in the bilateral midcingulate cortex, left
      postcentral gyrus, and left precuneus/inferior parietal lobule. However, no
      relationship was found between the mean ALFF signal values of the different areas
      and the clinical manifestations in HM. CONCLUSION: The HM patients were affected
      with brain dysfunction in many regions, which may indicate the presence of
      neurobiological changes involving deficits in language understanding and
      attentional control in HM patients.

PMID- 27881922
TI  - Effectiveness of etofenamate for treatment of knee osteoarthritis: a randomized
      controlled trial.
AB  - The intramuscular application of etofenamate in the treatment of knee
      osteoarthritis was not observed in the existing English language literature. The
      objectives of this study were to compare the efficacy of etofenamate versus
      hyaluronic acid (HA) in reducing joint pain and functional improvement for mild
      to moderate knee osteoarthritis. The patients were randomly divided into
      etofenamate (n=29) and HA (n=30) groups. Intramuscular etofenamate injection was
      administered as a series of seven intramuscular injections at intervals of 1 day.
      Intra-articular HA injection was administered as a series of three intra
      articular injections at intervals of 1 week. Clinical evaluation was made before
      the first injection and again both 6 and 12 months after the last injection. The
      evaluation consisted of patient-assessed pain on a visual analog scale (VAS) and
      on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
      Statistical significance was found for the etofenamate group when comparing
      preinjection with 12 months postinjection VAS scores (P<0.05). Statistical
      significance was also found for the HA group when comparing preinjection with 12
      months postinjection VAS and WOMAC scores (P<0.05). However, there was no
      significant difference between the etofenamate and HA groups in terms of VAS or
      WOMAC scores measured at 12 months after injection (P>0.05). Results from this
      study indicated that, etofenamate treatment was not significantly more effective
      than HA treatment. However, both methods were effective and successful in
      treating knee osteoarthritis.

PMID- 27881923
TI  - Predictive value of serum uric acid in hospitalized adolescents and adults with
      acute asthma.
AB  - BACKGROUND: High serum uric acid (sUA) is an indicator of oxidative stress and is
      linked to tissue hypoxia in asthma. The objective of this case series was to
      investigate the prognostic role of sUA in patients with acute asthma
      exacerbations and the link between sUA and spirometric lung tests. PATIENTS AND
      METHODS: This cross-sectional observational study included 120 patients with
      acute asthma exacerbations and 120 controls, categorized according to peak
      expiratory flow rate into moderate, and severe and life-threatening asthma. On
      admission, a detailed history was obtained and investigations were carried out
      regarding oxygen saturation (SaO2), arterial blood gas, spirometry, sUA, number
      of asthma exacerbations, smoking status, history of previous hospitalization,
      intensive care unit admission, and mechanical ventilation. RESULTS: The current
      study revealed higher sUA in asthmatic patients compared with healthy subjects
      and in severe asthma patients compared with moderate asthma patients (P<0.001). A
      positive correlation of sUA with asthma severity, number of asthma exacerbations
      and smoking index (r=0.6, 0.42 and 0.29, respectively, P<0.001) and a negative
      correlation of sUA with SaO2, partial pressure of arterial oxygen (PaO2), percent
      predicted forced vital capacity, percent predicted forced expiratory volume
      (FEV%) and peak expiratory flow rate percent of predicted (PEFR%; r=-0.48, -0.29,
      -0.44, -0.44 and -0.66, respectively, P<0.001) were observed. Degree of asthma
      severity, number of asthma exacerbations, and smoking index were significant
      predictors of high sUA (R2=0.43, P<0.001) in multiple linear regression model 1.
      SaO2 and PEFR% were significant predictors of high uric acid (R2=0.50, P<0.001)
      in model 2. The sensitivity and specificity of sUA in predicting severity of
      asthma at the cutoff point of 6.3 mg/dL were 80% and 90%, respectively. The odds
      ratios of sUA, number of asthma exacerbations, and asthma duration were 5.4, 1.95
      and 1.3, respectively. CONCLUSION: sUA may be a useful marker of predictive value
      of severity of asthma exacerbations.

PMID- 27881924
TI  - Rodent models of diabetic nephropathy: their utility and limitations.
AB  - Diabetic nephropathy is the most common cause of end-stage renal disease.
      Therefore, novel therapies for the suppression of diabetic nephropathy must be
      developed. Rodent models are useful for elucidating the pathogenesis of diseases
      and testing novel therapies, and many type 1 and type 2 diabetic rodent models
      have been established for the study of diabetes and diabetic complications.
      Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type
      1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice
      that overexpress calmodulin in pancreatic beta-cells serve as a genetic model of
      type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats,
      Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats
      serve as rodent models of type 2 diabetes. An animal model of diabetic
      nephropathy should exhibit progressive albuminuria and a decrease in renal
      function, as well as the characteristic histological changes in the glomeruli and
      the tubulointerstitial lesions that are observed in cases of human diabetic
      nephropathy. A rodent model that strongly exhibits all these features of human
      diabetic nephropathy has not yet been developed. However, the currently available
      rodent models of diabetes can be useful in the study of diabetic nephropathy by
      increasing our understanding of the features of each diabetic rodent model.
      Furthermore, the genetic background and strain of each mouse model result in
      differences in susceptibility to diabetic nephropathy with albuminuria and the
      development of glomerular and tubulointerstitial lesions. Therefore, the
      validation of an animal model reproducing human diabetic nephropathy will
      significantly facilitate our understanding of the underlying genetic mechanisms
      that contribute to the development of diabetic nephropathy. In this review, we
      focus on rodent models of diabetes and discuss the utility and limitations of
      these models for the study of diabetic nephropathy.

PMID- 27881925
TI  - Efficacy and tolerability balance of oxycodone/naloxone and tapentadol in chronic
      low back pain with a neuropathic component: a blinded end point analysis of
      randomly selected routine data from 12-week prospective open-label observations.
AB  - OBJECTIVE: To evaluate the benefit-risk profile (BRP) of oxycodone/naloxone (OXN)
      and tapentadol (TAP) in patients with chronic low back pain (cLBP) with a
      neuropathic component (NC) in routine clinical practice. METHODS: This was a
      blinded end point analysis of randomly selected 12-week routine/open-label data
      of the German Pain Registry on adult patients with cLBP-NC who initiated an index
      treatment in compliance with the current German prescribing information between
      1st January and 31st October 2015 (OXN/TAP, n=128/133). Primary end point was
      defined as a composite of three efficacy components (>=30% improvement of pain,
      pain-related disability, and quality of life each at the end of observation vs
      baseline) and three tolerability components (normal bowel function, absence of
      either central nervous system side effects, and treatment-emergent adverse event
      [TEAE]-related treatment discontinuation during the observation period) adopted
      to reflect BRP assessments under real-life conditions. RESULTS: Demographic as
      well as baseline and pretreatment characteristics were comparable for the
      randomly selected data sets of both index groups without any indicators for
      critical selection biases. Treatment with OXN resulted formally in a BRP
      noninferior to that of TAP and showed a significantly higher primary end point
      response vs TAP (39.8% vs 25.6%, odds ratio: 1.93; P=0.014), due to superior
      analgesic effects. Between-group differences increased with stricter response
      definitions for all three efficacy components in favor of OXN: >=30%/>=50%/>=70%
      response rates for OXN vs TAP were seen for pain intensity in 85.2%/67.2%/39.1%
      vs 83.5%/54.1%/15.8% (P= ns/0.031/<0.001), for pain-related disability in
      78.1%/64.8%/43.8% vs 66.9%/50.4%/24.8% (P=0.043/0.018/0.001), and for quality of
      life in 76.6%/68.0%/50.0% vs 63.9%/54.1%/34.6% (P=0.026/0.022/0.017). Overall,
      OXN vs TAP treatments were well tolerated, and proportions of patients who either
      maintained a normal bowel function (68.0% vs 72.2%), reported no central nervous
      system side effects (91.4% vs 89.5%), or completed the 12-week evaluation period
      without any TEAE-related treatment discontinuations (93.0% vs 92.5%) were similar
      for both index medications (P= ns for each comparison). CONCLUSION: In daily
      practice, the BRP of OXN proved to be noninferior to that of TAP in patients with
      cLBP-NC, but showed a superior efficacy if stricter analgesic response
      definitions were evaluated.

PMID- 27881926
TI  - Improving pain care through implementation of the Stepped Care Model at a
      multisite community health center.
AB  - PURPOSE: Treating pain in primary care is challenging. Primary care providers
      (PCPs) receive limited training in pain care and express low confidence in their
      knowledge and ability to manage pain effectively. Models to improve pain outcomes
      have been developed, but not formally implemented in safety net practices where
      pain is particularly common. This study evaluated the impact of implementing the
      Stepped Care Model for Pain Management (SCM-PM) at a large, multisite Federally
      Qualified Health Center. METHODS: The Promoting Action on Research Implementation
      in Health Services framework guided the implementation of the SCM-PM. The
      multicomponent intervention included: education on pain care, new protocols for
      pain assessment and management, implementation of an opioid management dashboard,
      telehealth consultations, and enhanced onsite specialty resources. Participants
      included 25 PCPs and their patients with chronic pain (3,357 preintervention and
      4,385 postintervention) cared for at Community Health Center, Inc. Data were
      collected from the electronic health record and supplemented by chart reviews.
      Surveys were administered to PCPs to assess knowledge, attitudes, and confidence.
      RESULTS: Providers' pain knowledge scores increased to an average of 11% from
      baseline; self-rated confidence in ability to manage pain also increased. Use of
      opioid treatment agreements and urine drug screens increased significantly by
      27.3% and 22.6%, respectively. Significant improvements were also noted in
      documentation of pain, pain treatment, and pain follow-up. Referrals to
      behavioral health providers for patients with pain increased by 5.96% (P=0.009).
      There was no significant change in opioid prescribing. CONCLUSION: Implementation
      of the SCM-PM resulted in clinically significant improvements in several quality
      of pain care outcomes. These findings, if sustained, may translate into improved
      patient outcomes.

PMID- 27881927
TI  - Appearance of fetal pain could be associated with maturation of the
      mesodiencephalic structures.
AB  - Fetal pain remains a controversial subject both in terms of recognizing its
      existence and the time-frame within which it appears. This article investigates
      the hypothesis that pain perception during development is not related to any
      determined structures of the central nervous system (CNS), on the contrary, the
      process of perception could be made with any structure satisfying conditions that
      the perception of pain is the organization, identification, and interpretation of
      sensory information in order to represent and understand the environment.
      According to this definition, chronic decerebrate and decorticate experimental
      animals, anencephalic, and hydranencephalic patients demonstrate that the basic,
      most general, appropriate interaction with the environment can be achieved with a
      functional mesodiencephalon (brain stem, and diencephalon) as the hierarchically
      highest structure of the CNS during development. In intact fetuses, this
      structure shows signs of sufficient maturation starting from the 15th week of
      gestation. Bearing in mind the dominant role of the reticular formation of the
      brain stem, which is marked by a wide divergence of afferent information, a sense
      of pain transmitted through it is diffuse and can dominate the overall perception
      of the fetus. The threshold for tactile stimuli is lower at earlier stages of
      gestation. The pain inhibition mechanisms are not sufficiently developed during
      intrauterine development, which is another factor that leads to increased
      intensity of pain in the fetus. As a conclusion it could be proposed that the
      fetus is exposed to rudimentary painful stimuli starting from the 15th gestation
      week and that it is extremely sensitive to painful stimuli.

PMID- 27881929
TI  - Rasch analysis of the Western Ontario Osteoarthritis of the Shoulder index - the
      Danish version.
AB  - PURPOSE: The Western Ontario Osteoarthritis of the Shoulder (WOOS) index is a
      disease-specific, patient-reported, 19-question survey that measures the quality
      of life among patients with osteoarthritis (OA). The purpose of this study was to
      validate the Danish version of WOOS for OA and fractures (FRs) using modern test
      theory. PATIENTS AND METHODS: The study included 1,987 arthroplasties in 1,943
      patients that were reported to the Danish Shoulder Arthroplasty Register between
      2006 and 2011. These included 847 OA and 1,140 FR cases. RESULTS: Principal
      component analysis indicated the unidimensionality of WOOS. The person
      reliabilities showed a floor-ceiling effect, indicating that a dichotomy was the
      best fit for the WOOS scale. For OA, WOOS showed good reliability (item and
      person reliability of 0.98 and 0.76) and good targeting, with a person mean of 
      0.56 logits. FR also showed good targeting (person mean of -0.08) and good
      reliability (item and person reliabilities of 1.00 and 0.86, respectively). All
      WOOS items fit well with the OA sample except items 5 and 6 (pertaining to
      grinding and the influence of weather). In addition, item 6 showed signs of
      degrading the scale with an outfit mean square of 2.46. Only item 6 showed a
      misfit for FR with no sign of scale degradation. The residual principal component
      analysis confirmed the unidimensionality of FR but not OA. Six items displayed
      clinically significant differential item functioning between OA and FR.
      CONCLUSION: Rasch analysis showed that WOOS had a good fit with the Rasch model
      when used as a dichotomous scale for OA and FR. However, the results were valid
      only when WOOS was divided into two categories with a threshold of 950 (50% of
      the maximum score). For the use of WOOS in future clinical research, we recommend
      that a dichotomous score be reported as a measure of clinical failure in OA and
      FR.

PMID- 27881928
TI  - Internet use and addiction among medical students of Universiti Sultan Zainal
      Abidin, Malaysia.
AB  - BACKGROUND: The use of Internet has now become indispensable, and the technology
      has revolutionized the medical education and practice worldwide. Currently,
      medical students and professionals have an enormous opportunity to keep them
      always updated with the exponential growth of knowledge because of potential
      progression of Internet throughout the world that enables them to become a
      lifelong learner. Internet addiction is a widespread phenomenon among students
      and academicians at universities in Malaysia. Students use the Internet for
      recreational purpose and personal and professional development. The Internet has
      become an integral part of day-to-day life of the university students, including
      medical students. The aim of the present study was to examine the Internet use
      and addiction among students of Universiti Sultan Zainal Abidin, Malaysia.
      METHODS: This was a cross-sectional study in which a questionnaire, Internet
      Addiction Diagnostic Questionnaire, developed by the Center for Internet
      Addiction, USA, was used. One hundred forty-nine medical students of Universiti
      Sultan Zainal Abidin participated in this study. Data were analyzed using
      Statistical Package for the Social Sciences software. RESULTS: The mean scores
      were 44.9+/-14.05 and 41.4+/-13.05 for male and female participants,
      respectively, which indicated that both the genders were suffering from mild
      Internet addiction. CONCLUSION: This study shows almost similar level of Internet
      usage among medical students irrespective of their socioeconomic background, with
      no statistically significant (p>0.05) differences, except among the years of
      study (p=0.007). Overall, from the research data and having worked with this
      cohort very closely, Universiti Sultan Zainal Abidin medical students can be
      labeled as wonted and recurring users of the Internet. Nevertheless, it is very
      difficult to define as Internet addicts or pathological users of the Internet
      because of small sample size and cross-sectional study.

PMID- 27881931
TI  - Proposed learning strategies of medical students in a clinical rotation in
      obstetrics and gynecology: a descriptive study.

PMID- 27881930
TI  - Psychological consequences of childhood obesity: psychiatric comorbidity and
      prevention.
AB  - Childhood obesity is one of the most serious public health challenges of the 21st
      century with far-reaching and enduring adverse consequences for health outcomes.
      Over 42 million children <5 years worldwide are estimated to be overweight (OW)
      or obese (OB), and if current trends continue, then an estimated 70 million
      children will be OW or OB by 2025. The purpose of this review was to focus on
      psychiatric, psychological, and psychosocial consequences of childhood obesity
      (OBy) to include a broad range of international studies. The aim was to establish
      what has recently changed in relation to the common psychological consequences
      associated with childhood OBy. A systematic search was conducted in MEDLINE, Web
      of Science, and the Cochrane Library for articles presenting information on the
      identification or prevention of psychiatric morbidity in childhood obesity.
      Relevant data were extracted and narratively reviewed. Findings established
      childhood OW/OBy was negatively associated with psychological comorbidities, such
      as depression, poorer perceived lower scores on health-related quality of life,
      emotional and behavioral disorders, and self-esteem during childhood. Evidence
      related to the association between attention-deficit/hyperactivity disorder
      (ADHD) and OBy remains unconvincing because of various findings from studies. OW
      children were more likely to experience multiple associated psychosocial problems
      than their healthy-weight peers, which may be adversely influenced by OBy stigma,
      teasing, and bullying. OBy stigma, teasing, and bullying are pervasive and can
      have serious consequences for emotional and physical health and performance. It
      remains unclear as to whether psychiatric disorders and psychological problems
      are a cause or a consequence of childhood obesity or whether common factors
      promote both obesity and psychiatric disturbances in susceptible children and
      adolescents. A cohesive and strategic approach to tackle this current obesity
      epidemic is necessary to combat this increasing trend which is compromising the
      health and well-being of the young generation and seriously impinging on
      resources and economic costs.

PMID- 27881932
TI  - Bayesian analysis of heterogeneous treatment effects for patient-centered
      outcomes research.
AB  - Evaluation of heterogeneity of treatment effect (HTE) is an essential aspect of
      personalized medicine and patient-centered outcomes research. Our goal in this
      article is to promote the use of Bayesian methods for subgroup analysis and to
      lower the barriers to their implementation by describing the ways in which the
      companion software beanz can facilitate these types of analyses. To advance this
      goal, we describe several key Bayesian models for investigating HTE and outline
      the ways in which they are well-suited to address many of the commonly cited
      challenges in the study of HTE. Topics highlighted include shrinkage estimation,
      model choice, sensitivity analysis, and posterior predictive checking. A case
      study is presented in which we demonstrate the use of the methods discussed.

PMID- 27881933
TI  - New bis(azobenzocrown)s with dodecylmethylmalonyl linkers as ionophores for
      sodium selective potentiometric sensors.
AB  - Novel biscrowns 1 and 2 were synthesized from 13-membered azobenzocrown ethers
      containing bromoalkylenoxy chains in para position relative to the azo group. The
      synthesized diester molecules are dodecylmethylmalonic acid derivatives differing
      by the linker length. The synthesized compounds have the potential of being used
      as sodium ionophores in ion-selective electrodes. They were characterized and
      used as ionophores in classic and miniature, solid contact (screen-printed and
      glassy carbon) membrane ion-selective electrodes. Compound 3, a similar monoester
      derivative of 13-membered azobenzocrown, was synthesized and used in membrane
      electrodes for comparison. Lipophilicity of new ionophores was determined by TLC.
      Lipophilicity of bis(azobenzocrown)s was found to be within the range of logPTLC
      = 12-13. It was observed that the particularly important selectivity coefficients
      logKNa,K determined for new electrodes, being logKNa,K = -2.5 and -2.6 (SSM, 0.1
      M), are better than those of the electrodes featuring seven out of the nine
      commercially available sodium ionophores. It was concluded that the ionophore 1
      creates, in acetone, with sodium iodide, complex of 1:1 stoichiometry (sandwich
      complex) with stability constant (logK) ca. 3.0.

PMID- 27881934
TI  - Modeling biological gradient formation: combining partial differential equations
      and Petri nets.
AB  - Both Petri nets and differential equations are important modeling tools for
      biological processes. In this paper we demonstrate how these two modeling
      techniques can be combined to describe biological gradient formation. Parameters
      derived from partial differential equation describing the process of gradient
      formation are incorporated in an abstract Petri net model. The quantitative
      aspects of the resulting model are validated through a case study of gradient
      formation in the fruit fly.

PMID- 27881935
TI  - Hair diseases: a big problem on a small surface.
AB  - Civilizational progress initially contributes to the problem of hair loss and
      then to alopecia as regards both frequency and therapeutic dilemmas. The work
      presents trichological problems which occur more rarely, i.e. drug-induced,
      anagen and telogen alopecia, congenital and acquired structural hair disorders,
      psychic disturbances concerning the hair as well as the hair during menopause.
      Then, the article briefly describes contagious (infectious) diseases as well as
      diseases with inflammatory etiology which are accompanied by exfoliation and
      (frequently) pruritus. Finally, alopecia cicatricans is discussed. Alopecia
      areata and androgenetic alopecia are omitted herein because they occur more often
      and will be described in another work. Any disproportions and upset balance
      concerning correct functioning of mechanisms within the scalp hair system are the
      evidence of pathologies.

PMID- 27881936
TI  - Autologous fat transfer to the subcutaneous tissue in the context of breast
      reconstructive procedures.
AB  - Autologous fat transfer (AFT) is an appropriate technique for aesthetic
      rejuvenation of the face, aesthetic enhancement of hands, correction of the
      facial appearance in various disorders and constitutes a surgical alternative of
      treatment of numerous breast deformities ranging from distorting posttraumatic
      scars, post-eczema lesions, post-burn deformities to partial or total breast
      reconstruction. Our work is aimed to familiarize dermatologists with the
      technique of harvesting and implanting the aspirate of adipose cells in patients
      consulted for deformities of the breast. In addition, the review summarizes the
      most common applications of AFT in the breast reconstructive procedures. In
      summary, AFT is an oncologically safe, relatively complication-free, minimally
      invasive surgical technique, which can be used to correct a wide range of
      deformities, which are commonly seen by dermatologists, in the area of the face,
      trunk and extremities. The procedure can correct a wide range of breast
      deformities, from contour or single quadrant deformities up to the state after
      mastectomy.

PMID- 27881937
TI  - "Better do not touch" and other superstitions concerning melanoma: the cross
      sectional web-based survey.
AB  - INTRODUCTION: To the authors' best knowledge, there are no data regarding the
      prevalence of superstitions concerning melanoma among internet users. AIM: To
      evaluate the prevalence and identify reasons for superstitions associated with
      excision of pigmented skin lesions as well as to assess the frequency of this
      procedure. MATERIAL AND METHODS: Readers of the scientific portal were invited to
      complete a fully anonymous e-questionnaire. After collection of questionnaires
      (5,154) and eliminating incomplete ones, 4,919 surveys were analysed. RESULTS: A
      total of 4,104 (83.4%) respondents have been aware that the total surgical
      excision is the only efficient way of melanoma treatment. This familiarity was
      related to increased skin cancer awareness but was not linked to regular skin
      self-examination. Over half of the surveyed agreed that "it is better not to
      touch naevi". Moreover, 3,510 (71.3%) individuals believed that naevi located in
      "harmed places" may turn into melanoma. CONCLUSIONS: Superstitions associated
      with surgical treatment of melanoma are widespread. Conducting educational
      campaigns is necessary, particularly among young people, whose dangerous tanning
      behaviours are important risk factors for melanoma occurrence in their later
      life.

PMID- 27881938
TI  - Are interleukin-15 and -22 a new pathogenic factor in pustular palmoplantar
      psoriasis?
AB  - INTRODUCTION: Pustular palmoplantar psoriasis (PPP) is a rare type of psoriasis
      affecting mainly distal parts of the limbs. Despite numerous theories about
      etiology of PPP, the pathogenesis still remains unclear. Recent data indicate
      that interleukin (IL)-15, IL-17 and IL-22 enhance a proinflammatory response in
      certain skin inflammatory diseases such as psoriasis and atopic dermatitis. There
      is also evidence that anti-endomysial (anti-EMA) and anti-gliadin (AGA)
      antibodies are engaged in PPP development. AIM: To assess IL-15, IL-17, IL-22
      serum levels and evaluate the presence of anti-endomysial and anti-gliadin
      antibodies in patients with PPP. MATERIAL AND METHODS: The study group consisted
      of 20 females of the mean age of 51.8 suffering from PPP. Additionally 29 healthy
      individuals, age and sex matched, served as controls. ELISA was performed to
      evaluate serum IL-15, IL-17, IL-22 concentrations while an indirect
      immunofluorescence test (IIF) was used to determine anti-EMA and AGA presence.
      RESULTS: The mean value of IL-15 and IL-22 serum concentrations was significantly
      higher in the study group than in the control group (IL-15: 6.48 vs. 4.88 pg/ml;
      IL-22: 81.47 vs. 4.90 pg/ml, respectively; p < 0.05 for all comparisons). The IL
      17 serum level in the study group was higher when compared to the control group
      (2.0 vs. 0.75 pg/ml), however the results were not statistically significant (p =
      0.26). There were no anti-EMA and AGA antibodies detected, both in the control
      and study group. CONCLUSIONS: The results obtained may suggest involvement of IL
      15 and IL-22 in the pathogenesis of PPP.

PMID- 27881940
TI  - The ischemia modified albumin and mean platelet volume levels in patients with
      Behcet's disease.
AB  - INTRODUCTION: Behcet's disease (BD) is a chronic inflammatory disorder with
      endothelial dysfunction. Ischemia-modified albumin (IMA) is a marker used in the
      detection of diseases associated with oxidative stress, vascular endothelial cell
      dysfunction and ischemia. Mean platelet volume (MPV) signifies the platelet
      function and activity. AIM: To show whether MPV and IMA are useful in revealing
      the oxidative stress and the risk of thrombosis in patients with BD. MATERIAL AND
      METHODS: Twenty-six patients with BD and 28 healthy volunteers as a control group
      over 18 years of age were included in the study. Serum IMA and MPV levels were
      analyzed in both groups. RESULTS: The mean MPV values were identified as 0.86 +/
      0.15 and 0.82 +/-0.08 (in the BD and control groups, respectively; p = 0.188) and
      the mean IMA values were 9.39 +/-0.73 and 9.17 +/-1.09 (in the BD and control
      groups, respectively; p = 0.275). There were no statistically significant
      differences between the groups. The IMA values of BD patients who were in the
      active phase were significant as compared to inactive BD patients and control
      groups (p = 0.041). The IMA and MPV values of the thrombotic patients, non
      thrombotic patients and control groups were not significant. CONCLUSIONS:
      Ischemia-modified albumin may be a helpful marker of possible complications
      during an active period of BD.

PMID- 27881939
TI  - Can pregnancy-associated plasma protein-A be a marker for the assessment of
      atherosclerosis risk in patients with chronic plaque psoriasis?
AB  - INTRODUCTION: Psoriasis is an immune-mediated chronic inflammatory dermatosis.
      Several studies have shown that patients with psoriasis have a much greater risk
      of cardiovascular diseases than the normal population. The chronic inflammation
      observed in psoriasis is thought to have a role in the development of
      atherosclerosis and vascular endothelial injury. AIM: To examine serum pregnancy
      associated plasma protein-A (PAPP-A) levels, which has been regarded as a marker
      of early stage atherosclerosis in patients with psoriasis that do not have
      concurrent conventional cardiovascular risk markers. MATERIAL AND METHODS: Forty
      one patients diagnosed with a chronic plaque type of psoriasis and 42 equally
      matched healthy volunteers were included in this study. The PAPP-A levels were
      compared between patient and control groups and the association between PAPP-A
      levels and disease duration and severity were evaluated in the patient group.
      RESULTS: Statistically, serum PAPP-A levels were significantly higher in the
      psoriasis group than in the control group (p = 0.015). Serum PAPP-A levels were
      found to be positively correlated with severity (p = 0.036, r = 0.329) and
      duration (p = 0.014, r = 0.269) of the disease. CONCLUSIONS: As a marker of early
      stage atherosclerosis, PAPP-A levels were elevated in the psoriasis group and
      were correlated with disease duration and severity. This elevation reveals the
      presence of atherosclerosis in patients with psoriasis. Further studies are
      needed to confirm the use of PAPP-A as an available and inexpensive screening
      test and cardiovascular risk assessment for all centers.

PMID- 27881941
TI  - Erythrocyte zinc level in patients with atopic dermatitis and its relation to
      SCORAD index.
AB  - INTRODUCTION: Atopic dermatitis (AD) is a chronic, pruritic inflammatory disease,
      characterized by a relapsing-remitting course. The pathogenesis of atopic
      dermatitis is not completely understood, although the disorder appears to result
      from the complex interaction between immune abnormalities, genetic and
      environmental factors. Trace elements are essential for normal functioning of the
      immune system. AIM: To determine zinc levels in serum and erythrocytes of
      patients with AD using an atomic absorption spectrometric technique and to
      investigate the relationship between those levels and disease activity. MATERIAL
      AND METHODS: Sixty-seven patients and 49 controls were enrolled into the study.
      The disease severity of AD patients was determined according to the Scoring
      Atopic Dermatitis (SCORAD) index. We measured zinc levels in serum and
      erythrocytes by the atomic absorption spectrophotometric technique. RESULTS:
      Erythrocyte zinc levels were significantly lower in AD patients than in the
      control group (p < 0.001), whereas serum zinc levels did not differ between the
      groups (p = 0.148). In the AD patient group there was a negative correlation
      between the SCORAD score and erythrocyte zinc levels (r = -0.791; p < 0.001).
      CONCLUSIONS: The negative relationship between disease severity and erythrocyte
      zinc levels might suggest an immunopathological link between AD progression and
      intracellular zinc metabolism.

PMID- 27881942
TI  - Allergic rhinitis, bronchial asthma and other allergies in patients with
      Alzheimer's disease: unnoticed issue.
AB  - INTRODUCTION: Allergic diseases are becoming more prevalent in elderly patients.
      Allergic diseases have been observed in patients with Alzheimer's disease (AD).
      The prevalence of atopic bronchial asthma, allergic rhinitis and atopic
      dermatitis was analyzed in such elderly Polish population. AIM: Analysis of the
      presence of allergic diseases in the patients with AD in Poland, including
      asthma, allergic rhinoconjunctivitis and atopic dermatitis. MATERIAL AND METHODS:
      The recruitment of subjects with AD was conducted at 6 sites representative of
      Polish rural and urban areas, and 1060 subjects with a mean age of 69.2 +/-5.1
      years were screened. Medical examinations, an original questionnaire, skin prick
      testing for common aeroallergens and appropriate serum-specific IgE assays were
      performed. RESULTS: Probable atopy was diagnosed in 234 (22.1%) analyzed
      patients, including 127 women (21.5% of women) and 234 men (22.8% of men). The
      average prevalence associated with age and sex in this population for bronchial
      asthma was 2.9%, atopic dermatitis/eczema was 0.6%, seasonal allergic rhinitis
      was 6.6%, perennial allergic rhinitis was 11.1% and polymorphous atopic disease
      was 4.4%. The most frequent positive results were recorded for the following
      allergens: mixed grass, Dermatophagoides pteronyssinus, Dermatophagoides farinae
      and Alternaria. CONCLUSIONS: One-fifth of diagnosed patients with AD have
      allergic disease requiring treatment.

PMID- 27881943
TI  - Number and size of acquired melanocytic nevi and affecting risk factors in cases
      admitted to the dermatology clinic.
AB  - INTRODUCTION: The size and number of acquired melanocytic nevi (AMN) and presence
      of dysplastic nevi are the leading risk factors that should be recognized in the
      development of malignant melanoma. AIM: To evaluate AMN and risk factors in the
      development of AMN in all age groups admitted to a dermatology outpatient clinic.
      MATERIAL AND METHODS: Four hundred and twelve patients who were admitted to the
      dermatology outpatient clinic for any dermatological symptom and who accepted to
      participate in the study were randomly included in the study. For each case,
      background-family history and dermatological findings were recorded. All AMN
      observed in the patients were dermatoscopically examined. RESULTS: The presence
      of more than 50 nevi was significantly higher in males, in individuals who had a
      history of sunburn and smokers. The number of nevi that were 5 mm and below was
      found to be higher in individuals who regularly sunbathed their face/body, in
      individuals using sunscreen, in individuals who had a history of sunburn, smokers
      and alcohol users. The number of nevi that were above 5 mm was higher in smokers.
      The total dermatoscopy score between 4.75 and 5.45 was found to be higher in
      individuals who had more than 50 nevi, in individuals exposed to more than one
      chemical substance and in alcohol users. CONCLUSIONS: When determining the
      patient's risk factors, factors such as the patient's sunbathing habits and
      chemical substance exposure features should be taken into consideration besides
      the number and size of nevi.

PMID- 27881944
TI  - -2518 A/G MCP-1 but not -403 G/A RANTES gene polymorphism is associated with
      enhanced risk of basal cell carcinoma.
AB  - INTRODUCTION: Polymorphic variants of MCP-1 and RANTES genes and their protein
      serum levels have been implicated in the increased risk and severity of several
      malignancies. However, the subject has not been explored in basal cell carcinoma
      (BCC) patients so far. AIM: To investigate the association between monocyte
      chemoattractant protein 1 (MCP-1) (-2518 A/G) and RANTES (-403 G/A) polymorphism
      and risk and clinical course of BCC. MATERIAL AND METHODS: The study group
      consisted of 150 unrelated patients with BCC and 140 healthy, unrelated, age- and
      sex-matched volunteers. The polymorphisms were analysed using the amplification
      refractory mutation system polymerase chain reaction method (ARMS-PCR) and single
      specific primer-polymerase chain reaction (SSP-PCR). Serum cytokine levels were
      measured with ELISA. RESULTS: The presence of the MCP-1 -2518 GG genotype was
      statistically more frequent in BCC patients and it increased the risk of BCC (OR
      = 2.63, p = 0.003). Genotype -330 GG was statistically more common in patients
      with less advanced tumours (OR = 2.8, p = 0.017). Monocyte chemoattractant
      protein 1 serum level was statistically higher with GG genotype. In the BCC group
      MCP-1 serum levels were decreased. Neither polymorphic variants of RANTES nor the
      chemokine serum concentration differed significantly between the study groups.
      CONCLUSIONS: These findings suggest that -2518 A/G MCP-1 polymorphism may be
      involved in BCC pathogenesis.

PMID- 27881945
TI  - Difficult management of a patient with pr10 related anaphylaxis.

PMID- 27881946
TI  - Atypical clinical presentation of lichen planus bullous in a systemic sclerosis
      patient.

PMID- 27881947
TI  - Elastosis perforans serpiginosa: a review of the literature and our own
      experience.

PMID- 27881948
TI  - Reproducibility and Bias in Healthy Brain Segmentation: Comparison of Two Popular
      Neuroimaging Platforms.
AB  - We evaluated and compared the performance of two popular neuroimaging processing
      platforms: Statistical Parametric Mapping (SPM) and FMRIB Software Library (FSL).
      We focused on comparing brain segmentations using Kirby21, a magnetic resonance
      imaging (MRI) replication study with 21 subjects and two scans per subject
      conducted only a few hours apart. We tested within- and between-platform
      segmentation reliability both at the whole brain and in 10 regions of interest
      (ROIs). For a range of fixed probability thresholds we found no differences
      between-scans within-platform, but large differences between-platforms. We have
      also found very large differences between- and within-platforms when probability
      thresholds were changed. A randomized blinded reader study indicated that: (1)
      SPM and FSL performed well in terms of gray matter segmentation; (2) SPM and FSL
      performed poorly in terms of white matter segmentation; and (3) FSL slightly
      outperformed SPM in terms of CSF segmentation. We also found that tissue class
      probability thresholds can have profound effects on segmentation results. We
      conclude that the reproducibility of neuroimaging studies depends on the
      neuroimaging software-processing platform and tissue probability thresholds. Our
      results suggest that probability thresholds may not be comparable across
      platforms and consistency of results may be improved by estimating a probability
      threshold correspondence function between SPM and FSL.

PMID- 27881949
TI  - Neural Mechanisms of the Transformation from Objective Value to Subjective
      Utility: Converting from Count to Worth.
AB  - When deciding, we aim to choose the "best" possible outcome. This is not just
      selection of the option that is the most numerous or physically largest, as
      options are translated from objective value (count) to subjective value (worth or
      utility). We localized the neural instantiation of the value-to-utility
      transformation to the dorsal anterior midcingulate cortex (daMCC), with
      independent replication. The daMCC encodes the context-specific information
      necessary to convert from count to worth. This encoding is not simply a
      representation of utility or preference, but the interaction of the two.
      Specifically, the relationship of brain activation to value is dependent on
      individual preference, with both positive and negative slopes across the
      population depending on whether each individual's preference results in
      enhancement or diminishment of the valuation. For a given value, across
      participants, enhanced daMCC activation corresponds to diminished subjective
      valuation, deactivation to enhanced subjective valuation, and non-modulated
      activation with non-modulated subjective valuation. Further, functional
      connectivity analyses identified brain regions (positive connectivity with the
      inferior frontal gyrus and negative connectivity with the nucleus accumbens)
      through which contextual information may be integrated into the daMCC and allow
      for outputs to modulate valuation signals. All analyses were replicated through
      an independent within-study replication, with initial testing in the gains domain
      and replication in the intermixed and mirrored losses trials. We also present and
      discuss an ancillary finding: we were unable to identify parametric value signals
      for losses through whole-brain analyses, and ROI analyses of the vmPFC presented
      non-modulation across loss value levels. These results identify the neural locus
      of the value-to-utility transformation, and provide a specific computational
      function for the daMCC in the production of subjective valuation through the
      integration of value, context, and preferences.

PMID- 27881950
TI  - A New Approach of Modified Submerged Patch Clamp Recording Reveals Interneuronal
      Dynamics during Epileptiform Oscillations.
AB  - Highlights Simultaneous epileptiform LFPs and single-cell activity can be
      recorded in the membrane chamber.Interneuron firing can be linked to epileptiform
      high frequency activity.Fast ripples, unique to chronic epilepsy, can be modeled
      in ex vivo tissue from TeNT-treated rats. Traditionally, visually-guided patch
      clamp in brain slices using submerged recording conditions has been required to
      characterize the activity of individual neurons. However, due to limited oxygen
      availability, submerged conditions truncate fast network oscillations including
      epileptiform activity. Thus, it is technically challenging to study the
      contribution of individual identified neurons to fast network activity. The
      membrane chamber is a submerged-style recording chamber, modified to enhance
      oxygen supply to the slice, which we use to demonstrate the ability to record
      single-cell activity during in vitro epilepsy. We elicited epileptiform activity
      using 9 mM potassium and simultaneously recorded from fluorescently labeled
      interneurons. Epileptiform discharges were more reliable than in standard
      submerged conditions. During these synchronous discharges interneuron firing
      frequency increased and action potential amplitude progressively decreased. The
      firing of 15 interneurons was significantly correlated with epileptiform high
      frequency activity (HFA; ~100-500 Hz) cycles. We also recorded epileptiform
      activity in tissue prepared from chronically epileptic rats, treated with
      intrahippocampal tetanus neurotoxin. Four of these slices generated fast ripple
      activity, unique to chronic epilepsy. We showed the membrane chamber is a
      promising new in vitro environment facilitating patch clamp recordings in acute
      epilepsy models. Further, we showed that chronic epilepsy can be better modeled
      using ex vivo brain slices. These findings demonstrate that the membrane chamber
      facilitates previously challenging investigations into the neuronal correlates of
      epileptiform activity in vitro.

PMID- 27881952
TI  - Tissue-type Plasminogen Activator (tPA) Modulates the Postsynaptic Response of
      Cerebral Cortical Neurons to the Presynaptic Release of Glutamate.
AB  - Tissue-type plasminogen activator (tPA) is a serine proteinase released by the
      presynaptic terminal of cerebral cortical neurons following membrane
      depolarization (Echeverry et al., 2010). Recent studies indicate that the release
      of tPA triggers the synaptic vesicle cycle and promotes the exocytosis (Wu et
      al., 2015) and endocytic retrieval (Yepes et al., 2016) of glutamate-containing
      synaptic vesicles. Here we used electron microscopy, proteomics, quantitative
      phosphoproteomics, biochemical analyses with extracts of the postsynaptic density
      (PSD), and an animal model of cerebral ischemia with mice overexpressing neuronal
      tPA to study whether the presynaptic release of tPA also has an effect on the
      postsynaptic terminal. We found that tPA has a bidirectional effect on the
      composition of the PSD of cerebral cortical neurons that is independent of the
      generation of plasmin and the presynaptic release of glutamate, but depends on
      the baseline level of neuronal activity and the extracellular concentrations of
      calcium (Ca2+). Accordingly, in neurons that are either inactive or incubated
      with low Ca2+ concentrations tPA induces phosphorylation and accumulation in the
      PSD of the Ca2+/calmodulin-dependent protein kinase IIalpha (pCaMKIIalpha),
      followed by pCaMKIIalpha-mediated phosphorylation and synaptic recruitment of
      GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors. In contrast, in neurons with previously increased baseline levels of
      pCaMKIIalpha in the PSD due to neuronal depolarization in vivo or incubation with
      high concentrations of either Ca2+ or glutamate in vitro, tPA induces
      pCaMKIIalpha and pGluR1 dephosphorylation and their subsequent removal from the
      PSD. We found that these effects of tPA are mediated by synaptic N-methyl-D
      aspartate (NMDA) receptors and cyclin-dependent kinase 5 (Cdk5)-induced
      phosphorylation of the protein phosphatase 1 (PP1) at T320. Our data indicate
      that by regulating the pCaMKIIalpha/PP1 balance in the PSD tPA acts as a
      homeostatic regulator of the postsynaptic response of cerebral cortical neurons
      to the presynaptic release of glutamate.

PMID- 27881954
TI  - Editorial: Structural and Functional Organisation of the Prefrontal Cortex.

PMID- 27881951
TI  - Neuronal Gene Targets of NF-kappaB and Their Dysregulation in Alzheimer's
      Disease.
AB  - Although, better known for its role in inflammation, the transcription factor
      nuclear factor kappa B (NF-kappaB) has more recently been implicated in synaptic
      plasticity, learning, and memory. This has been, in part, to the discovery of its
      localization not just in glia, cells that are integral to mediating the
      inflammatory process in the brain, but also neurons. Several effectors of
      neuronal NF-kappaB have been identified, including calcium, inflammatory
      cytokines (i.e., tumor necrosis factor alpha), and the induction of experimental
      paradigms thought to reflect learning and memory at the cellular level (i.e.,
      long-term potentiation). NF-kappaB is also activated after learning and memory
      formation in vivo. In turn, activation of NF-kappaB can elicit either suppression
      or activation of other genes. Studies are only beginning to elucidate the
      multitude of neuronal gene targets of NF-kappaB in the normal brain, but research
      to date has confirmed targets involved in a wide array of cellular processes,
      including cell signaling and growth, neurotransmission, redox signaling, and gene
      regulation. Further, several lines of research confirm dysregulation of NF-kappaB
      in Alzheimer's disease (AD), a disorder characterized clinically by a profound
      deficit in the ability to form new memories. AD-related neuropathology includes
      the characteristic amyloid beta plaque formation and neurofibrillary tangles.
      Although, such neuropathological findings have been hypothesized to contribute to
      memory deficits in AD, research has identified perturbations at the cellular and
      synaptic level that occur even prior to more gross pathologies, including
      transcriptional dysregulation. Indeed, synaptic disturbances appear to be a
      significant correlate of cognitive deficits in AD. Given the more recently
      identified role for NF-kappaB in memory and synaptic transmission in the normal
      brain, the expansive network of gene targets of NF-kappaB, and its dysregulation
      in AD, a thorough understanding of NF-kappaB-related signaling in AD is warranted
      and may have important implications for uncovering treatments for the disease.
      This review aims to provide a comprehensive view of our current understanding of
      the gene targets of this transcription factor in neurons in the intact brain and
      provide an overview of studies investigating NF-kappaB signaling, including its
      downstream targets, in the AD brain as a means of uncovering the basic
      physiological mechanisms by which memory becomes fragile in the disease.

PMID- 27881953
TI  - Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions.
AB  - Brain networks, localized or brain-wide, exist only at the cellular level, i.e.,
      between specific pre- and post-synaptic neurons, which are connected through
      functionally diverse synapses located at specific points of their cell membranes.
      "Connectomics" is the emerging subfield of neuroanatomy explicitly aimed at
      elucidating the wiring of brain networks with cellular resolution and a
      quantified accuracy. Such data are indispensable for realistic modeling of brain
      circuitry and function. A connectomic analysis, therefore, needs to identify and
      measure the soma, dendrites, axonal path, and branching patterns together with
      the synapses and gap junctions of the neurons involved in any given brain circuit
      or network. However, because of the submicron caliber, 3D complexity, and high
      packing density of most such structures, as well as the fact that axons
      frequently extend over long distances to make synapses in remote brain regions,
      creating connectomic maps is technically challenging and requires multi-scale
      approaches, Such approaches involve the combination of the most sensitive cell
      labeling and analysis methods available, as well as the development of new ones
      able to resolve individual cells and synapses with increasing high-throughput. In
      this review, we provide an overview of recently introduced high-resolution
      methods, which researchers wanting to enter the field of connectomics may
      consider. It includes several molecular labeling tools, some of which
      specifically label synapses, and covers a number of novel imaging tools such as
      brain clearing protocols and microscopy approaches. Apart from describing the
      tools, we also provide an assessment of their qualities. The criteria we use
      assess the qualities that tools need in order to contribute to deciphering the
      key levels of circuit organization. We conclude with a brief future outlook for
      neuroanatomic research, computational methods, and network modeling, where we
      also point out several outstanding issues like structure-function relations and
      the complexity of neural models.

PMID- 27881955
TI  - Response: Commentary: Perceptual learning in autism: over-specificity and
      possible remedies.

PMID- 27881957
TI  - The Effects of Excitatory and Inhibitory Social Cues on Cocaine-Seeking Behavior.
AB  - Social partners influence the likelihood of using drugs, developing a substance
      use disorder and relapse to drug use after a period of abstinence. Preclinical
      studies report that social cues influence the acquisition of cocaine use, the
      escalation of cocaine use over time, and the compulsive patterns of cocaine use
      that emerge during an extended binge. The purpose of this study was to examine
      the effects of social cues on the reinstatement of cocaine-seeking behavior after
      a period of abstinence. Male rats were obtained at weaning, assigned to triads
      (three rats/cage), reared to adulthood and implanted with intravenous catheters.
      Rats from each triad were then assigned to one of three conditions: (1) test rats
      were trained to self-administer cocaine and were tested for reinstatement; (2)
      cocaine partners were trained to self-administer cocaine and were predictive of
      response-contingent cocaine delivery; and (3) abstinent partners were not given
      access to cocaine and were predictive of extinction. The test rats alternated
      social partners every 5 days for 20 days such that responding was reinforced with
      cocaine in the presence of the cocaine partner (S+) for 10 days and not
      reinforced with cocaine in the presence of the abstinent partner (S-) for 10
      days. Responding of the test rats was then extinguished over 7 days under
      isolated conditions. Tests of reinstatement were then conducted in the presence
      of the cocaine partner and abstinent partner under extinction conditions. Neither
      social partner reinstated responding relative to that observed on the final day
      of extinction; however, responding was greater in the presence of the cocaine
      partner (S+) than the abstinent partner (S-) during the reinstatement test. These
      data fail to demonstrate that a social partner reinstates cocaine-seeking
      behavior after a period of abstinence, but they do indicate that social partners
      can serve as either excitatory or inhibitory discriminative stimuli to influence
      drug-seeking responses.

PMID- 27881956
TI  - Ovarian Sex Hormones Modulate Compulsive, Affective and Cognitive Functions in A
      Non-Induced Mouse Model of Obsessive-Compulsive Disorder.
AB  - There is currently a lack of understanding of how surgical menopause can
      influence obsessions, compulsions and associated affective and cognitive
      functions in female obsessive-compulsive disorder (OCD) patients. Early menopause
      in women due to surgical removal of ovaries not only causes dramatic hormonal
      changes, but also may induce affective and cognitive disorders. Here, we tested
      if surgical removal of ovaries (ovariectomy, OVX), which mimics surgical
      menopause in humans, would result in exacerbation of compulsive, affective and
      cognitive behaviors in mice strains that exhibit a spontaneous compulsive-like
      phenotype. Female mice from compulsive-like BIG, non-compulsive SMALL and
      randomly-bred Control strains were subjected to OVX or sham-surgery. After 7 days
      animals were tested for nest building and marble burying to measure compulsive
      like behavior. The elevated plus maze and open field tests measured anxiety-like
      behaviors, while memory was assessed by the novel object recognition. Acute OVX
      resulted in exacerbation of compulsive-like and anxiety-like behaviors in
      compulsive-like BIG mice. No significant effects of OVX were observed for the non
      compulsive SMALL and Control strains. Object recognition memory was impaired in
      compulsive-like BIG female mice compared to the Control mice, without an effect
      of OVX on the BIG mice. We also tested whether 17 beta-estradiol (E2) or
      progesterone (P4) could reverse the effects of OVX. E2, but not P4, attenuated
      the compulsive-like behaviors in compulsive-like BIG OVX female mice. The actions
      of the sex steroids on anxiety-like behaviors in OVX females were strain and
      behavioral test dependent. Altogether, our results indicate that already existing
      compulsions can be worsened during acute ovarian deprivation concomitant with
      exacerbation of affective behaviors and responses to hormonal intervention in OVX
      female mice can be influenced by genetic background.

PMID- 27881959
TI  - Effective Connectivity within the Mesocorticolimbic System during Resting-State
      in Cocaine Users.
AB  - Objective: Although effective connectivity between brain regions has been
      examined in cocaine users during tasks, no effective connectivity study has been
      conducted on cocaine users during resting-state. In the present functional
      magnetic resonance imaging study, we examined effective connectivity in resting
      brain, between the brain regions within the mesocorticolimbic dopamine system,
      implicated in reward and motivated behavior, while the chronic cocaine users and
      controls took part in a resting-state scan by using a spectral Dynamic causal
      modeling (spDCM) approach. Method: As part of a study testing cocaine cue
      reactivity in cocaine users (Ray et al., 2015b), 20 non-treatment seeking cocaine
      smoking (abstinent for at least 3 days) and 17 control participants completed a
      resting state scan and an anatomical scan. A mean voxel-based time series data
      extracted from four key brain areas (ventral tegmental area, VTA; nucleus
      accumbens, NAc; hippocampus, medial frontal cortex) within the mesocorticolimbic
      dopamine system during resting-state from the cocaine and control participants
      were used as input to the spDCM program to generate spDCM analysis outputs.
      Results: Compared to the control group, the cocaine group had higher effective
      connectivity from the VTA to NAc, hippocampus and medial frontal cortex. In
      contrast, the control group showed a higher effective connectivity from the
      medial frontal cortex to VTA, from the NAc to medial frontal cortex, and on the
      hippocampus self-loop. Conclusions: The present study is the first to show that
      during resting-state in abstaining cocaine users compared to controls, the VTA
      initiates an enhanced effective connectivity to NAc, hippocampus and medial
      frontal cortex areas within the mesocorticolimbic dopamine system, the brain's
      reward system. Future studies of effective connectivity analysis during resting
      state may eventually be used to monitor treatment outcome.

PMID- 27881958
TI  - Motor Cortex Neurostimulation Technologies for Chronic Post-stroke Pain:
      Implications of Tissue Damage on Stimulation Currents.
AB  - Background: Central post stroke pain (CPSP) is a highly refractory syndrome that
      can occur after stroke. Primary motor cortex (M1) brain stimulation using
      epidural brain stimulation (EBS), transcranial magnetic stimulation (TMS), and
      transcranial direct current stimulation (tDCS) have been explored as potential
      therapies for CPSP. These techniques have demonstrated variable clinical
      efficacy. It is hypothesized that changes in the stimulating currents that are
      caused by stroke-induced changes in brain tissue conductivity limit the efficacy
      of these techniques. Methods: We generated MRI-guided finite element models of
      the current density distributions in the human head and brain with and without
      chronic focal cortical infarctions during EBS, TMS, and tDCS. We studied the
      change in the stimulating current density distributions' magnitude, orientation,
      and maxima locations between the different models. Results: Changes in electrical
      properties at stroke boundaries altered the distribution of stimulation currents
      in magnitude, location, and orientation. Current density magnitude alterations
      were larger for the non-invasive techniques (i.e., tDCS and TMS) than for EBS.
      Nonetheless, the lesion also altered currents during EBS. The spatial shift of
      peak current density, relative to the size of the stimulation source, was largest
      for EBS. Conclusion: In order to maximize therapeutic efficiency,
      neurostimulation trials need to account for the impact of anatomically disrupted
      neural tissues on the location, orientation, and magnitude of exogenously applied
      currents. The relative current-neuronal structure should be considered when
      planning stimulation treatment, especially across techniques (e.g., using TMS to
      predict EBS response). We postulate that the effects of altered tissue properties
      in stroke regions may impact stimulation induced analgesic effects and/or lead to
      highly variable outcomes during brain stimulation treatments in CPSP.

PMID- 27881960
TI  - Testing the Limits of Skill Transfer for Scrabble Experts in Behavior and Brain.
AB  - We investigated transfer of the skills developed by competitive Scrabble players.
      Previous studies reported superior performance for Scrabble experts on the
      lexical decision task (LDT), suggesting near transfer of Scrabble skills. Here we
      investigated the potential for far transfer to a symbol decision task (SDT); in
      particular, transfer of enhanced long-term working memory for vertically
      presented stimuli. Our behavioral results showed no evidence for far transfer.
      Despite years of intensive practice, Scrabble experts were no faster and no more
      accurate than controls in the SDT. However, our fMRI and EEG data from the SDT
      suggest that the neural repertoire that Scrabble experts develop supports task
      performance even outside of the practiced domain, in a non-linguistic context.
      The regions engaged during the SDT were different across groups: controls engaged
      temporal-frontal regions, whereas Scrabble experts engaged posterior visual and
      temporal-parietal regions. In Scrabble experts, activity related to Scrabble
      skill (anagramming scores) included regions associated with visual-spatial
      processing and long-term working memory, and overlapped with regions previously
      shown to be associated with Scrabble expertise in the near transfer task (LDT).
      Analysis of source waveforms within these regions showed that participants with
      higher anagramming scores had larger P300 amplitudes, potentially reflecting
      greater working memory capacity, or less variability in the participants who
      performed the task more efficiently. Thus, the neuroimaging results provide
      evidence of brain transfer in the absence of behavioral transfer, providing new
      clues about the consequences of long-term training associated with competitive
      Scrabble expertise.

PMID- 27881962
TI  - Cigarette Smoking-Induced Cardiac Hypertrophy, Vascular Inflammation and Injury
      Are Attenuated by Antioxidant Supplementation in an Animal Model.
AB  - Background: Cardiovascular diseases are the leading causes of morbidity and
      mortality worldwide. Cigarette smoking remains a global health epidemic with
      associated detrimental effects on the cardiovascular system. In this work, we
      investigated the effects of cigarette smoke exposure on cardiovascular system in
      an animal model. The study then evaluated the effects of antioxidants (AO),
      represented by pomegranate juice, on cigarette smoke induced cardiovascular
      injury. This study aims at evaluating the effect of pomegranate juice
      supplementation on the cardiovascular system of an experimental rat model of
      smoke exposure. Methods: Adult rats were divided into four different groups:
      Control, Cigarette smoking (CS), AO, and CS + AO. Cigarette smoke exposure was
      for 4 weeks (5 days of exposure/week) and AO group received pomegranate juice
      while other groups received placebo. Assessment of cardiovascular injury was
      documented by assessing different parameters of cardiovascular injury mediators
      including: (1) cardiac hypertrophy, (2) oxidative stress, (3) expression of
      inflammatory markers, (4) expression of Bradykinin receptor 1 (Bdkrb1),
      Bradykinin receptor 2 (Bdkrb2), and (5) altered expression of
      fibrotic/atherogenic markers [(Fibronectin (Fn1) and leptin receptor (ObR))].
      Results: Data from this work demonstrated that cigarette smoke exposure induced
      cardiac hypertrophy, which was reduced upon administration of pomegranate in CS +
      AO group. Cigarette smoke exposure was associated with elevation in oxidative
      stress, significant increase in the expression of IL-1beta, TNFalpha, Fn1, and
      ObR in rat's aorta. In addition, an increase in aortic calcification was observed
      after 1 month of cigarette smoke exposure. Furthermore, cigarette smoke induced a
      significant up regulation in Bdkrb1 expression level. Finally, pomegranate
      supplementation exhibited cardiovascular protection assessed by the above
      findings and partly contributed to ameliorating cardiac hypertrophy in cigarette
      smoke exposed animals. Conclusion: Findings from this work showed that cigarette
      smoking exposure is associated with significant cardiovascular pathology such as
      cardiac hypertrophy, inflammation, pro-fibrotic, and atherogenic markers and
      aortic calcification in an animal model as assessed 1 month post exposure.
      Antioxidant supplementation prevented cardiac hypertrophy and attenuated
      indicators of atherosclerosis markers associated with cigarette smoke exposure.

PMID- 27881961
TI  - Functional Connectivity of Child and Adolescent Attention Deficit Hyperactivity
      Disorder Patients: Correlation with IQ.
AB  - Attention deficit hyperactivity disorder (ADHD) is a pervasive neuropsychological
      disorder that affects both children and adolescents. Child and adolescent ADHD
      patients exhibit different behavioral symptoms such as hyperactivity and
      impulsivity, but not much connectivity research exists to help explain these
      differences. We analyzed openly accessible resting-state functional magnetic
      resonance imaging (rs-fMRI) data on 112 patients (28 child ADHD, 28 adolescent
      ADHD, 28 child normal control (NC), and 28 adolescent NC). We used group
      independent component analysis (ICA) and weighted degree values to identify
      interaction effects of age (child and adolescent) and symptom (ADHD and NC) in
      brain networks. The frontoparietal network showed significant interaction effects
      (p = 0.0068). The frontoparietal network is known to be related to hyperactive
      and impulsive behaviors. Intelligence quotient (IQ) is an important factor in
      ADHD, and we predicted IQ scores using the results of our connectivity analysis.
      IQ was predicted using degree centrality values of networks with significant
      interaction effects of age and symptom. Actual and predicted IQ scores
      demonstrated significant correlation values, with an error of about 10%. Our
      study might provide imaging biomarkers for future ADHD and intelligence studies.

PMID- 27881964
TI  - Corrigendum: Bioassay-Guided Isolation of Sesquiterpene Coumarins from Ferula
      narthex Bioss: A New Anticancer Agent.
AB  - [This corrects the article on p. 26 in vol. 7, PMID: 26909039.].

PMID- 27881963
TI  - Angiogenesis Inhibitors for the Treatment of Hepatocellular Carcinoma.
AB  - Background: Angiogenesis inhibitors have become an important therapeutic approach
      in the treatment of hepatocellular carcinoma (HCC) patients. The therapeutic
      inhibition of angiogenesis of Sorafenib in increasing overall survival of
      patients with HCC is a fundamental element of the treatment of this disease.
      Considering the heterogeneous aspects of HCC and to boost therapeutic efficacy,
      prevail over drug resistance and lessen toxicity, adding antiangiogenic drugs to
      antiblastic chemotherapy (AC), radiation therapy or other targeted drugs have
      been evaluated. The matter is additionally complicated by the combination of
      antiangiogenesis with further AC or biologic drugs. To date, no planned approach
      to understand which patients are more responsive to a given type of
      antiangiogenic treatment is available. Conclusion: Large investments in the
      clinical research are essential to improve treatment response and minimize
      toxicities for patients with HCC. Future investigations will need to focus on
      utilizing patterns of genetic information to classify HCC into groups that
      display similar prognosis and treatment sensitivity, and combining targeted
      therapies with AC producing enhanced anti-tumor effect. In this review the
      current panel of available antiangiogenic therapies for the treatment of HCC have
      been analyzed. In addition current clinical trials are also reported herein.

PMID- 27881967
TI  - The Composer's Program Note for Newly Written Classical Music: Content and
      Intentions.
AB  - In concerts of western classical music the provision of a program note is a
      widespread practice dating back to the 18th century and still commonly in use.
      Program notes tend to inform listeners and performers about historical context,
      composer biographical details, and compositional thinking. However, the scant
      program note research conducted to date reveals that program notes may not foster
      understanding or enhance listener enjoyment as previously assumed. In the case of
      canonic works, performers and listeners may already be familiar with much of the
      program note information. This is not so in the case of newly composed works,
      which formed the basis of the exploratory study reported here. This article
      reports the views of 17 living contemporary composers on their writing of program
      notes for their own works. In particular, the study sought to understand the
      intended recipient, role and the content of composer-written program notes.
      Participating composers identified three main roles for their program notes: to
      shape a performer's interpretation of the work; to guide, engage or direct the
      listener and/or performer; and as collaborative mode of communication between the
      composer, performer, and listener. For some composers, this collaboration was
      intended to result in "performative listening" in which listeners were actively
      engaged in bringing each composition to life. This was also described as a form
      of empathy that results in the co-construction of the musical experience.
      Overall, composers avoided giving too much personal information and they provided
      performers with more structural information. However, composers did not agree on
      whether the same information should be provided to both performers and listeners.
      Composers' responses problematize the view of a program note as a simple
      statement from writer to recipient, indicating instead a more complex set of
      relations at play between composer, performer, listener, and the work itself.
      These relations are illustrated in a model. There are implications for program
      note writers and readers, and for educators. Future research might seek to
      enhance understanding of program notes, including whether the written program
      note is the most effective format for communications about music.

PMID- 27881966
TI  - The Effect of Implicit Preferences on Food Consumption: Moderating Role of Ego
      Depletion and Impulsivity.
AB  - Ego depletion has been found to moderate the effect of implicit preferences on
      food consumption, such that implicit preferences predict consumption only under a
      depleted state. The present study tested how trait impulsivity impacts the effect
      of implicit preferences on food consumption in a depleted condition. Trait
      impulsivity was measured by means of self-report and a stop signal task. Results
      showed that both self-reported impulsivity and behavioral impulsivity moderated
      the 'depletion and then eating according to implicit preferences' effect, albeit
      in different ways. Participants high in self-reported impulsivity and low in
      behavioral impulsivity were more vulnerable to the effect of depletion on eating.
      The implications of these results for extant theories are discussed. Future
      research is needed to verify whether or not trait impulsivity is associated with
      vulnerability to depletion across different self-control domains.

PMID- 27881968
TI  - Influences on and Measures of Unintentional Group Synchrony.
AB  - Many instances of large-scale coordination occur in real-life social situations
      without the explicit awareness of the individuals involved. While the majority of
      research to date has examined dyadic interactions - those between two individuals
      - during intentional or deliberate coordination, the present review surveys the
      handful of recent studies investigating behavioral and physiological synchrony
      across groups of more than two people when coordination was not an explicit goal.
      Both minimal (e.g., visual information, shared location) and naturalistic (e.g.,
      choir voice section, family relationship) group interactions appear to promote
      unintentional group synchrony although they have so far only been studied
      separately. State differences in unintentional group synchrony, or the relative
      presence of coordination in various conditions, have tended to be assessed
      differently, such as using correlation-type relationships, compared to its
      temporal dynamics, or changes over time in the degree of coordination, which
      appear to be best captured using phase differences. Simultaneously evaluating
      behavioral, physiological, and social responses as well systematically comparing
      different synchrony measures could further our understanding of the influences on
      and measures of group synchrony, allowing us to move away from studying
      individual persons responding to static laboratory stimuli and toward
      investigating collective experiences in natural, dynamic social interactions.

PMID- 27881965
TI  - Fundamental Role of Methylenetetrahydrofolate Reductase 677 C -> T Genotype and
      Flavin Compounds in Biochemical Phenotypes for Schizophrenia and Schizoaffective
      Psychosis.
AB  - The Mental Health Biomarker Project (2010-2016) explored variables for psychosis
      in schizophrenia and schizoaffective disorder. Blood samples from 67, highly
      characterized symptomatic cases and 67 gender and age matched control
      participants were analyzed for methyl tetrahydrofolate reductase (MTHFR) 677C ->
      T gene variants and for vitamin B6, B12 and D, folate, unbound copper, zinc
      cofactors for enzymes in the methylation cycle, and related catecholamine
      pathways. Urine samples were analyzed for indole-catecholamines, their
      metabolites, and oxidative-stress marker, hydroxylpyrolline-2-one (HPL). Rating
      scales were Brief Psychiatric Rating Scale, Positive and Negative Syndrome Scale,
      Global Assessment of Function scale, Clinical Global Impression (CGI) score, and
      Social and Occupational Functioning Assessment Scale (SOFAS). Analysis used
      Spearman's correlates, receiver operating characteristics and structural equation
      modeling (SEM). The correlative pattern of variables in the overall participant
      sample strongly implicated monoamine oxidase (MAO) enzyme inactivity so the
      significant role of MAO's cofactor flavin adenine nucleotide and its precursor
      flavin adenine mononucleotide (FMN) within the biochemical pathways was
      investigated and confirmed as 71% on SEM of the total sample. Splitting the data
      sets for MTHFR 677C -> T polymorphism variants coding for the MTHFR enzyme,
      discovered that biochemistry variables relating to the wild-type enzyme differed
      markedly in pattern from those coded by the homozygous variant and that the
      hereozygous-variant pattern resembled the wild-type-coded pattern. The MTHFR 677C
      -> T-wild and -heterozygous gene variants have a pattern of depleted vitamin
      cofactors characteristic of flavin insufficiency with under-methylation and
      severe oxidative stress. The second homozygous MTHFR 677TT pattern related to
      elevated copper:zinc ratio and a vitamin pattern related to flavin sufficiency
      and risk of over-methylation. The two gene variants and their different
      biochemical phenotypes govern findings in relationship to case-identification,
      illness severity, duration of illness, and functional disability in schizophrenia
      and schizoaffective psychosis, and establish a basis for trials of gene-guided
      precision treatment for the management of psychosis.

PMID- 27881969
TI  - A Self-Reference Effect on Memory for People: We Are Particularly Good at
      Retrieving People Named Like Us.
AB  - In the present study, it was evaluated whether one's own name may produce a self
      reference bias in memory for people. Results from Experiment 1 indicated that, in
      a verbal fluency task, participants recalled a greater number of known (familiar
      or famous) people with the same first name as their own than did paired
      participants, and vice versa. In the first experiment, paired participants knew
      each other but were not close. Experiment 2 examined whether this self-reference
      effect would still occur when the comparison target was a close other. This
      experiment showed that such a self-reference bias also occurred even when the
      paired persons were close (partners or very good friends). Overall the present
      paper describes a new naturalistic case of the self-reference effect.

PMID- 27881970
TI  - The Potential of Virtual Reality for the Investigation of Awe.
AB  - The emotion of awe is characterized by the perception of vastness and a need for
      accommodation, which can include a positive and/or negative valence. While a
      number of studies have successfully manipulated this emotion, the issue of how to
      elicit particularly intense awe experiences in laboratory settings remains. We
      suggest that virtual reality (VR) is a particularly effective mood induction tool
      for eliciting awe. VR provides three key assets for improving awe. First, VR
      provides users with immersive and ecological yet controlled environments that can
      elicit a sense of "presence," the subjective experience of "being there" in a
      simulated reality. Further, VR can be used to generate complex, vast stimuli,
      which can target specific theoretical facets of awe. Finally, VR allows for
      convenient tracking of participants' behavior and physiological responses,
      allowing for more integrated assessment of emotional experience. We discussed the
      potential and challenges of the proposed approach with an emphasis on VR's
      capacity to raise the signal of reactions to emotions such as awe in laboratory
      settings.

PMID- 27881971
TI  - Familial Longevity Is Not Associated with Major Differences in the Hypothalamic
      Pituitary-Gonadal Axis in Healthy Middle-Aged Men.
AB  - CONTEXT: A trade-off between fertility and longevity possibly exists. The
      association of the male hypothalamic-pituitary-gonadal (HPG) axis with familial
      longevity has not yet been investigated. OBJECTIVE: To study 24-h hormone
      concentration profiles of the HPG axis in men enriched for familial longevity and
      controls. DESIGN: We frequently sampled blood over 24 h in 10 healthy middle-aged
      male offspring of nonagenarian participants from the Leiden Longevity Study
      together with 10 male age-matched controls. Individual 24-h luteinizing hormone
      (LH) and testosterone concentration profiles were analyzed by deconvolution
      analyses to estimate secretion parameters. Furthermore, the temporal relationship
      between LH and testosterone was assessed by cross-correlation analysis. We used
      (cross-)approximate entropy to quantify the strength of feedback and/or
      feedforward control of LH and testosterone secretion. RESULTS: Mean [95%
      confidence interval (CI)] total LH secretion of the offspring was 212 (156-268)
      U/L/24 h, which did not differ significantly (p = 0.51) from the total LH
      secretion of controls [186 (130-242) U/L/24 h]. Likewise, mean (95% CI) total
      testosterone secretion of the offspring [806 (671-941) nmol/L/24 h] and controls
      [811 (676-947) nmol/L/24 h] were similar (p = 0.95). Other parameters of LH and
      testosterone secretion were also not significantly different between offspring
      and controls. The temporal relationship between LH and testosterone and the
      strength of feedforward/feedback regulation within the HPG axis were similar
      between offspring of long-lived families and controls. CONCLUSION: This
      relatively small study suggests that in healthy male middle-aged participants,
      familial longevity is not associated with major differences in the HPG axis.
      Selection on both fertility and health may in part explain the results.

PMID- 27881972
TI  - Multilocus Sequence Typing Analysis of Carbapenem-Resistant Acinetobacter
      baumannii in a Chinese Burns Institute.
AB  - Acinetobacter baumannii is a leading pathogen responsible for nosocomial
      infections. The emergence of carbapenem-resistant A. baumannii (CRAB) has left
      few effective antibiotics for clinicians to use. To investigate the temporal
      evolutionary relationships among CRAB strains, we collected 248 CRAB isolates
      from a Chinese burns institute over 3 years. The prevalence of the OXA-23 gene
      was detected by polymerase chain reaction. Multilocus sequence typing was used to
      type the CRAB strains and eBURST was used to analyze their evolutionary
      relationships. Wound surfaces (41%), sputa (24%), catheters (15%), and bloods
      (14%) were the four dominant isolation sources. Except for minocycline (33.5%)
      and sulbactam/cefoperazone (74.6%), these CRAB strains showed high resistance
      rates (>90%) to 16 tested antibiotics. The 248 isolates fall into 26 sequence
      types (STs), including nine known STs and 17 unknown STs. The majority (230/248)
      of these isolates belong to clonal complex 92 (CC92), including eight isolates
      belonging to seven unreported STs. A new CC containing 11 isolates grouped into
      four new STs was identified. The OXA-23 gene was detected at high prevalence
      among the CRAB isolates and the prevalence rate among the various STs differed.
      The majority of the isolates displayed a close evolutionary relationship,
      suggesting that serious nosocomial spreading and nosocomial infections of CRAB
      have occurred in the burn unit. In conclusion, the main CC for CRAB in this
      Chinese burn unit remained unchanged during the 3-year study period, and a new CC
      was identified. CC92 was the dominant complex, and more attention should be
      directed toward monitoring the new CC we have identified herein.

PMID- 27881973
TI  - Livestock-Associated Methicillin Resistant Staphylococcus aureus (LA-MRSA) Clonal
      Complex (CC) 398 Isolated from UK Animals belong to European Lineages.
AB  - In recent years, there has been an increase in the number of livestock-associated
      methicillin resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398
      recovered from S. aureus isolated animals in the UK. To determine possible
      origins of 12 LA-MRSA CC398 isolates collected after screening more than a
      thousand S. aureus animal isolates from the UK between 2013 and 2015, whole
      genome sequences (WGS) of CC398 European, including UK, and non-European isolates
      from diverse animal hosts were compared. Phylogenetic reconstruction applied to
      WGS data to assess genetic relatedness of all 89 isolates, clustered the 12 UK
      CC398 LA-MRSA within the European sub-lineages, although on different nodes;
      implicating multiple independent incursions into the UK, as opposed to a single
      introduction followed by clonal expansion. Three UK isolates from healthy pigs
      and one from turkey clustered within the cassette chromosome recombinases ccr C
      S. aureus protein A (spa)-type t011 European sub-lineage and three UK isolates
      from horses within the ccrA2B2 t011 European sub-lineage. The remaining UK
      isolates, mostly from pigs, clustered within the t034 European lineage. Presence
      of virulence, antimicrobial (AMR), heavy metal (HMR), and disinfectant (DR)
      resistance genes were determined using an in-house pipeline. Most, including UK
      isolates, harbored resistance genes to >=3 antimicrobial classes in addition to
      beta-lactams. HMR genes were detected in most European ccrC positive isolates,
      with >80% harboring czrC, encoding zinc and cadmium resistance; in contrast ~60%
      ccrC isolates within non-European lineages and 6% ccrA2B2 isolates showed this
      characteristic. The UK turkey MRSA isolate did not harbor phiAVbeta avian
      prophage genes (SAAV_2008 and SAAV_2009) present in US MSSA isolates from turkey
      and pigs. Absence of some of the major human-associated MRSA toxigenic and
      virulence genes in the UK LA-MRSA animal isolates was not unexpected. Therefore,
      we can conclude that the 12 UK LA-MRSA isolates collected in the past 2 years
      most likely represent separate incursions into the UK from other European
      countries. The presence of zinc and cadmium resistance in all nine food animal
      isolates (pig and poultry), which was absent from the 3 horse isolates may
      suggest heavy metal use/exposure has a possible role in selection of some MRSA.

PMID- 27881974
TI  - The Microbiome and Occurrence of Methanotrophy in Carnivorous Sponges.
AB  - As shown by recent studies, filter-feeding sponges are known to host a wide
      variety of microorganisms. However, the microbial community of the non-filtering
      carnivorous sponges (Porifera, Cladorhizidae) has been the subject of less
      scrutiny. Here, we present the results from a comparative study of the
      methanotrophic carnivorous sponge Cladorhiza methanophila from a mud volcano-rich
      area at the Barbados Accretionary Prism, and five carnivorous species from the
      Jan Mayen Vent Field (JMVF) at the Arctic Mid-Ocean Ridge. Results from 16S rRNA
      microbiome data indicate the presence of a diverse assemblage of associated
      microorganisms in carnivorous sponges mainly from the Gamma- and
      Alphaproteobacteria, Flavobacteriaceae, and Thaumarchaeota. While the abundance
      of particular groups varied throughout the dataset, we found interesting
      similarities to previous microbiome results from non-carnivorous deep sea
      sponges, suggesting that the carnivorous sponges share characteristics of a
      previously hypothesized putative deep-sea sponge microbial community.
      Chemolithoautotrophic symbiosis was confirmed for C. methanophila through a
      microbial community with a high abundance of Methylococcales and very light
      isotopic delta13C and delta15N ratios (-60 to -660/00/3.5 to 5.20/00) compared to
      the other cladorhizid species (-22 to -240/00/8.5 to 10.50/00). We provide
      evidence for the presence of putative sulfur-oxidizing Gammaproteobacteria in the
      arctic cladorhizids; however, delta13C and delta15N signatures did not provide
      evidence for significant chemoautotrophic symbiosis in this case, and the
      slightly higher abundance of cladorhizids at the JMVF site compared to the nearby
      deep sea likely stem from an increased abundance of prey rather than a more
      direct vent association. The phylogenetic position of C. methanophila in relation
      to other carnivorous sponges was established using a three-gene phylogenetic
      analysis, and it was found to be closely related to other non-methanotrophic
      Cladorhiza species with a similar morphology included in the dataset, suggesting
      a recent origin for methanotrophy in this species. C. methanophila remains the
      only known carnivorous sponge with a strong, chemolithoautotrophic symbiont
      association, and methanotrophic symbiosis does not seem to be a widespread
      property within the Cladorhizidae.

PMID- 27881975
TI  - Membrane Complexes of Syntrophomonas wolfei Involved in Syntrophic Butyrate
      Degradation and Hydrogen Formation.
AB  - Syntrophic butyrate metabolism involves the thermodynamically unfavorable
      production of hydrogen and/or formate from the high potential electron donor,
      butyryl-CoA. Such redox reactions can occur only with energy input by a process
      called reverse electron transfer. Previous studies have demonstrated that
      hydrogen production from butyrate requires the presence of a proton gradient, but
      the biochemical machinery involved has not been clearly elucidated. In this
      study, the gene and enzyme systems involved in reverse electron transfer by
      Syntrophomonas wolfei were investigated using proteomic and gene expression
      approaches. S. wolfei was grown in co-culture with Methanospirillum hungatei or
      Dehalococcoides mccartyi under conditions requiring reverse electron transfer and
      compared to both axenic S. wolfei cultures and co-cultures grown in conditions
      that do not require reverse electron transfer. Blue native gel analysis of
      membranes solubilized from syntrophically grown cells revealed the presence of a
      membrane-bound hydrogenase, Hyd2, which exhibited hydrogenase activity during in
      gel assays. Bands containing a putative iron-sulfur (FeS) oxidoreductase were
      detected in membranes of crotonate-grown and butyrate grown S. wolfei cells. The
      genes for the corresponding hydrogenase subunits, hyd2ABC, were differentially
      expressed at higher levels during syntrophic butyrate growth when compared to
      growth on crotonate. The expression of the FeS oxidoreductase gene increased when
      S. wolfei was grown with M. hungatei. Additional membrane-associated proteins
      detected included FoF1 ATP synthase subunits and several membrane transporters
      that may aid syntrophic growth. Furthermore, syntrophic butyrate metabolism can
      proceed exclusively by interspecies hydrogen transfer, as demonstrated by growth
      with D. mccartyi, which is unable to use formate. These results argue for the
      importance of Hyd2 and FeS oxidoreductase in reverse electron transfer during
      syntrophic butyrate degradation.

PMID- 27881976
TI  - The Roles of Alpha-Momorcharin and Jasmonic Acid in Modulating the Response of
      Momordica charantia to Cucumber Mosaic Virus.
AB  - Alpha-momorcharin (alpha-MMC) is a type-I ribosome inactivating protein with a
      molecular weight of 29 kDa that is found in Momordica charantia, and has been
      shown to be effective against a broad range of human viruses as well as having
      anti-tumor activities. However, the role of endogenous alpha-MMC under viral
      infection and the mechanism of the anti-viral activities of alpha-MMC in plants
      are still unknown. To study the effect of alpha-MMC on plant viral defense and
      how alpha-MMC increases plant resistance to virus, the M. charantia-cucumber
      mosaic virus (CMV) interaction system was investigated. The results showed that
      the alpha-MMC level was positively correlated with the resistance of M. charantia
      to CMV. alpha-MMC treatment could alleviate photosystem damage and enhance the
      ratio of glutathione/glutathione disulfide in M. charantia under CMV infection.
      The relationship of alpha-MMC and defense related phytohormones, and their roles
      in plant defense were further investigated. alpha-MMC treatment led to a
      significant increase of jasmonic acid (JA) and vice versa, while there was no
      obvious relevance between salicylic acid and alpha-MMC. In addition, reactive
      oxygen species (ROS) were induced in alpha-MMC-pretreated plants, in a similar
      way to the ROS burst in JA-pretreated plants. The production of ROS in both
      ibuprofen (JA inhibitor) and (alpha-MMC+ibuprofen)-pretreated plants was reduced
      markedly, leading to a greater susceptibility of M. charantia to CMV. Our results
      indicate that the anti-viral activities of alpha-MMC in M. charantia may be
      accomplished through the JA related signaling pathway.

PMID- 27881977
TI  - Different Virus-Derived siRNAs Profiles between Leaves and Fruits in Cucumber
      Green Mottle Mosaic Virus-Infected Lagenaria siceraria Plants.
AB  - RNA silencing is an evolutionarily conserved antiviral mechanism, through which
      virus-derived small interfering RNAs (vsiRNAs) playing roles in host antiviral
      defense are produced in virus-infected plant. Deep sequencing technology has
      revolutionized the study on the interaction between virus and plant host through
      the analysis of vsiRNAs profile. However, comparison of vsiRNA profiles in
      different tissues from a same host plant has been rarely reported. In this study,
      the profiles of vsiRNAs from leaves and fruits of Lagenaria siceraria plants
      infected with Cucumber green mottle mosaic virus (CGMMV) were comprehensively
      characterized and compared. Many more vsiRNAs were present in infected leaves
      than in fruits. vsiRNAs from both leaves and fruits were mostly 21- and 22-nt in
      size as previously described in other virus-infected plants. Interestingly,
      vsiRNAs were predominantly produced from the viral positive strand RNAs in
      infected leaves, whereas in infected fruits they were derived equally from the
      positive and negative strands. Many leaf-specific positive vsiRNAs with lengths
      of 21-nt (2058) or 22-nt (3996) were identified but only six (21-nt) and one (22
      nt) positive vsiRNAs were found to be specific to fruits. vsiRNAs hotspots were
      only present in the 5'-terminal and 3'-terminal of viral positive strand in
      fruits, while multiple hotspots were identified in leaves. Differences in GC
      content and 5'-terminal nucleotide of vsiRNAs were also observed in the two
      organs. To our knowledge, this provides the first high-resolution comparison of
      vsiRNA profiles between different tissues of the same host plant.

PMID- 27881979
TI  - Cationic Nanostructures against Foodborne Pathogens.

PMID- 27881978
TI  - The Oxidosqualene Cyclase from the Oomycete Saprolegnia parasitica Synthesizes
      Lanosterol as a Single Product.
AB  - The first committed step of sterol biosynthesis is the cyclisation of 2,3
      oxidosqualene to form either lanosterol (LA) or cycloartenol (CA). This is
      catalyzed by an oxidosqualene cyclase (OSC). LA and CA are subsequently converted
      into various sterols by a series of enzyme reactions. The specificity of the OSC
      therefore determines the final composition of the end sterols of an organism.
      Despite the functional importance of OSCs, the determinants of their specificity
      are not well understood. In sterol-synthesizing oomycetes, recent bioinformatics,
      and metabolite analysis suggest that LA is produced. However, this catalytic
      activity has never been experimentally demonstrated. Here, we show that the OSC
      of the oomycete Saprolegnia parasitica, a severe pathogen of salmonid fish, has
      an uncommon sequence in a conserved motif important for specificity. We present
      phylogenetic analysis revealing that this sequence is common to sterol
      synthesizing oomycetes, as well as some plants, and hypothesize as to the
      evolutionary origin of some microbial sequences. We also demonstrate for the
      first time that a recombinant form of the OSC from S. parasitica produces LA
      exclusively. Our data pave the way for a detailed structural characterization of
      the protein and the possible development of specific inhibitors of oomycete OSCs
      for disease control in aquaculture.

PMID- 27881981
TI  - TCR/pMHC Interaction: Phenotypic Model for an Unsolved Enigma.
AB  - TCR-pMHC interaction is the keystone of the adaptive immune response. This
      process exhibits an impressive capacity of speed, sensitivity, and discrimination
      that allows detecting foreign pMHCs at very low concentration among much more
      abundant self-pMHC ligands. However, and despite over three decades of intensive
      research, the mechanisms by which this remarkable discrimination and sensitivity
      is attained remain controversial. In kinetic proofreading mechanisms (KPR), an
      increase of specificity occurs by reducing the sensitivity. To overcome this
      difficulty, more elaborate models including feedback processes or induced
      rebinding have been incorporated into the KPR scheme. Here a new approach based
      on the assumption that the proofreading chain behaves differently for foreign-
      and self-pMHC complexes has been integrated into a phenotypic model in which the
      complexes responsible for T cell activation stabilize (for foreign peptides) or
      weaken (for foreign peptides), resulting in a dramatic increase in sensitivity
      and specificity. Stabilization and destabilization of complexes may be caused by
      conformational changes, rebinding, or any other process leading to variations in
      the dissociation rate constants of the complexes transmitting the activation. The
      numerical solution and the analytical expression for the steady-state response as
      a function of koff(i) (i = 0, 1, ..., N, where C0, C1, ..., CN are the complexes
      in the proofreading chain) are provided. The activation chain speeds up, and
      larger increases in sensitivity and discrimination are obtained if the rate of
      activation along the proofreading chain increases for foreign pMHCs and decreases
      for self-ligands. Experimental implications and comparison with current models
      are discussed.

PMID- 27881980
TI  - Comparative Genomics of DNA Recombination and Repair in Cyanobacteria:
      Biotechnological Implications.
AB  - Cyanobacteria are fascinating photosynthetic prokaryotes that are regarded as the
      ancestors of the plant chloroplast; the purveyors of oxygen and biomass for the
      food chain; and promising cell factories for an environmentally friendly
      production of chemicals. In colonizing most waters and soils of our planet,
      cyanobacteria are inevitably challenged by environmental stresses that generate
      DNA damages. Furthermore, many strains engineered for biotechnological purposes
      can use DNA recombination to stop synthesizing the biotechnological product.
      Hence, it is important to study DNA recombination and repair in cyanobacteria for
      both basic and applied research. This review reports what is known in a few
      widely studied model cyanobacteria and what can be inferred by mining the
      sequenced genomes of morphologically and physiologically diverse strains. We show
      that cyanobacteria possess many E. coli-like DNA recombination and repair genes,
      and possibly other genes not yet identified. E. coli-homolog genes are unevenly
      distributed in cyanobacteria, in agreement with their wide genome diversity. Many
      genes are extremely well conserved in cyanobacteria (mutMS, radA, recA, recFO,
      recG, recN, ruvABC, ssb, and uvrABCD), even in small genomes, suggesting that
      they encode the core DNA repair process. In addition to these core genes, the
      marine Prochlorococcus and Synechococcus strains harbor recBCD (DNA
      recombination), umuCD (mutational DNA replication), as well as the key SOS genes
      lexA (regulation of the SOS system) and sulA (postponing of cell division until
      completion of DNA reparation). Hence, these strains could possess an E. coli-type
      SOS system. In contrast, several cyanobacteria endowed with larger genomes lack
      typical SOS genes. For examples, the two studied Gloeobacter strains lack alkB,
      lexA, and sulA; and Synechococcus PCC7942 has neither lexA nor recCD.
      Furthermore, the Synechocystis PCC6803 lexA product does not regulate DNA repair
      genes. Collectively, these findings indicate that not all cyanobacteria have an
      E. coli-type SOS system. Also interestingly, several cyanobacteria possess
      multiple copies of E. coli-like DNA repair genes, such as Acaryochloris marina
      MBIC11017 (2 alkB, 3 ogt, 7 recA, 3 recD, 2 ssb, 3 umuC, 4 umuD, and 8 xerC),
      Cyanothece ATCC51142 (2 lexA and 4 ruvC), and Nostoc PCC7120 (2 ssb and 3 xerC).

PMID- 27881983
TI  - High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs:
      Characteristics, Functions, and Regulation.
AB  - High endothelial venules (HEVs) and lymphatic vessels (LVs) are essential for the
      function of the immune system, by providing communication between the body and
      lymph nodes (LNs), specialized sites of antigen presentation and recognition.
      HEVs bring in naive and central memory cells and LVs transport antigen, antigen
      presenting cells, and lymphocytes in and out of LNs. Tertiary lymphoid organs
      (TLOs) are accumulations of lymphoid and stromal cells that arise and organize at
      ectopic sites in response to chronic inflammation in autoimmunity, microbial
      infection, graft rejection, and cancer. TLOs are distinguished from primary
      lymphoid organs - the thymus and bone marrow, and secondary lymphoid organs
      (SLOs) - the LNs, spleen, and Peyer's patches, in that they arise in response to
      inflammatory signals, rather than in ontogeny. TLOs usually do not have a capsule
      but are rather contained within the confines of another organ. Their structure,
      cellular composition, chemokine expression, and vascular and stromal support
      resemble SLOs and are the defining aspects of TLOs. T and B cells, antigen
      presenting cells, fibroblast reticular cells, and other stromal cells and
      vascular elements including HEVs and LVs are all typical components of TLOs. A
      key question is whether the HEVs and LVs play comparable roles and are regulated
      similarly to those in LNs. Data are presented that support this concept,
      especially with regard to TLO HEVs. Emerging data suggest that the functions and
      regulation of TLO LVs are also similar to those in LNs. These observations
      support the concept that TLOs are not merely cellular accumulations but are
      functional entities that provide sites to generate effector cells, and that their
      HEVs and LVs are crucial elements in those activities.

PMID- 27881984
TI  - Gene Discovery and Advances in Finger Millet [Eleusine coracana (L.) Gaertn.]
      Genomics-An Important Nutri-Cereal of Future.
AB  - The rapid strides in molecular marker technologies followed by genomics, and next
      generation sequencing advancements in three major crops (rice, maize and wheat)
      of the world have given opportunities for their use in the orphan, but highly
      valuable future crops, including finger millet [Eleusine coracana (L.) Gaertn.].
      Finger millet has many special agronomic and nutritional characteristics, which
      make it an indispensable crop in arid, semi-arid, hilly and tribal areas of India
      and Africa. The crop has proven its adaptability in harsh conditions and has
      shown resilience to climate change. The adaptability traits of finger millet have
      shown the advantage over major cereal grains under stress conditions, revealing
      it as a storehouse of important genomic resources for crop improvement. Although
      new technologies for genomic studies are now available, progress in identifying
      and tapping these important alleles or genes is lacking. RAPDs were the default
      choice for genetic diversity studies in the crop until the last decade, but the
      subsequent development of SSRs and comparative genomics paved the way for the
      marker assisted selection in finger millet. Resistance gene homologs from NBS-LRR
      region of finger millet for blast and sequence variants for nutritional traits
      from other cereals have been developed and used invariably. Population structure
      analysis studies exhibit 2-4 sub-populations in the finger millet gene pool with
      separate grouping of Indian and exotic genotypes. Recently, the omics
      technologies have been efficiently applied to understand the nutritional
      variation, drought tolerance and gene mining. Progress has also occurred with
      respect to transgenics development. This review presents the current
      biotechnological advancements along with research gaps and future perspective of
      genomic research in finger millet.

PMID- 27881982
TI  - Milestones of Hematopoietic Stem Cell Transplantation - From First Human Studies
      to Current Developments.
AB  - Since the early beginnings, in the 1950s, hematopoietic stem cell transplantation
      (HSCT) has become an established curative treatment for an increasing number of
      patients with life-threatening hematological, oncological, hereditary, and
      immunological diseases. This has become possible due to worldwide efforts of
      preclinical and clinical research focusing on issues of transplant immunology,
      reduction of transplant-associated morbidity, and mortality and efficient
      malignant disease eradication. The latter has been accomplished by potent graft
      versus-leukemia (GvL) effector cells contained in the stem cell graft. Exciting
      insights into the genetics of the human leukocyte antigen (HLA) system allowed
      improved donor selection, including HLA-identical related and unrelated donors.
      Besides bone marrow, other stem cell sources like granulocyte-colony stimulating
      mobilized peripheral blood stem cells and cord blood stem cells have been
      established in clinical routine. Use of reduced-intensity or non-myeloablative
      conditioning regimens has been associated with a marked reduction of non
      hematological toxicities and eventually, non-relapse mortality allowing older
      patients and individuals with comorbidities to undergo allogeneic HSCT and to
      benefit from GvL or antitumor effects. Whereas in the early years, malignant
      disease eradication by high-dose chemotherapy or radiotherapy was the ultimate
      goal; nowadays, allogeneic HSCT has been recognized as cellular immunotherapy
      relying prominently on immune mechanisms and to a lesser extent on non-specific
      direct cellular toxicity. This chapter will summarize the key milestones of HSCT
      and introduce current developments.

PMID- 27881986
TI  - The Parenchyma of Secondary Xylem and Its Critical Role in Tree Defense against
      Fungal Decay in Relation to the CODIT Model.
AB  - This review examines the roles that ray and axial parenchyma (RAP) plays against
      fungal pathogens in the secondary xylem of wood within the context of the CODIT
      model (Compartmentalization of Decay in Trees), a defense concept first conceived
      in the early 1970s by Alex Shigo. This model, simplistic in its design, shows how
      a large woody perennial is highly compartmented. Anatomical divisions in place at
      the time of infection or damage, (physical defense) alongside the 'active'
      response by the RAP during and after wounding work together in forming boundaries
      that function to restrict air or decay spread. The living parenchyma cells play a
      critical role in all of the four walls (differing anatomical constructs) that the
      model comprises. To understand how living cells in each of the walls of CODIT
      cooperate, we must have a clear vision of their complex interconnectivity from a
      three-dimensional perspective, along with knowledge of the huge variation in ray
      parenchyma (RP) and axial parenchyma (AP) abundance and patterns. Crucial
      patterns for defense encompass the symplastic continuum between both RP and AP
      and the dead tissues, with the latter including the vessel elements, libriform
      fibers, and imperforate tracheary elements (i.e., vasicentric and vascular
      tracheids). Also, the heartwood, a chemically altered antimicrobial non-living
      substance that forms the core of many trees, provides an integral part of the
      defense system. In the heartwood, dead RAP can play an important role in defense,
      depending on the genetic constitution of the species. Considering the array of
      functions that RAP are associated with, from capacitance, through to storage, and
      long-distance water transport, deciding how their role in defense fits into this
      suite of functions is a challenge for plant scientists, and likely depends on a
      range of factors. Here, we explore the important role of RAP in defense against
      fungal pathogens and the trade-offs involved from a viewpoint for structure
      function relations, while also examining how fungi can breach the defense system
      using an array of enzymes in conjunction with the physically intrusive hyphae.

PMID- 27881985
TI  - Pollen Aquaporins: The Solute Factor.
AB  - In the recent years, the biophysical properties and presumed physiological role
      of aquaporins (AQPs) have been expanded to specialized cells where water and
      solute exchange are crucial traits. Complex but unique processes such as stomatal
      movement or pollen hydration and germination have been addressed not only by
      identifying the specific AQP involved but also by studying how these proteins
      integrate and coordinate cellular activities and functions. In this review, we
      referred specifically to pollen-specific AQPs and analyzed what has been assumed
      in terms of transport properties and what has been found in terms of their
      physiological role. Unlike that in many other cells, the AQP machinery in mature
      pollen lacks plasma membrane intrinsic proteins, which are extensively studied
      for their high water capacity exchange. Instead, a variety of TIPs and NIPs are
      expressed in pollen. These findings have altered the initial understanding of
      AQPs and water exchange to consider specific and diverse solutes that might be
      critical to sustaining pollen's success. The spatial and temporal distribution of
      the pollen AQPs also reflects a regulatory mechanism that allowing a properly
      adjusting water and solute exchange.

PMID- 27881988
TI  - Identification of a Solanum pennellii Chromosome 4 Fruit Flavor and Nutritional
      Quality-Associated Metabolite QTL.
AB  - A major resource for tomato quality improvement and gene discovery is the
      collection of introgression lines (ILs) of cultivated Solanum lycopersicum that
      contain different, defined chromosomal segments derived from the wild tomato
      relative, S. pennellii. Among these lines, IL4-4, in which the bottom of S.
      lycopersicum (cv. M82) chromosome 4 is replaced by the corresponding S. pennellii
      segment, is altered in many primary and secondary metabolites, including many
      related to fruit flavor and nutritional quality. Here, we provide a comprehensive
      profile of IL4-4 ripe fruit metabolites, the transcriptome and fine mapping of
      sub-ILs. Remarkably, out of 327 quantified metabolites, 185 were significantly
      changed in IL4-4 fruit, compared to the control. These altered metabolites
      include volatile organic compounds, primary and secondary metabolites. Partial
      least squares enhanced discriminant analysis of the metabolite levels among sub
      ILs indicated that a genome region encompassing 20 putative open reading frames
      is responsible for most of the metabolic changes in IL4-4 fruit. This work
      provides comprehensive insights into IL4-4 fruit biochemistry, identifying a
      small region of the genome that has major effects on a large and diverse set of
      metabolites.

PMID- 27881987
TI  - Microscopic and Molecular Characterization of the Prehaustorial Resistance
      against Wheat Leaf Rust (Puccinia triticina) in Einkorn (Triticum monococcum).
AB  - Puccinia triticina f. sp. tritici (Eriks.), the causal agent of leaf rust, causes
      substantial yield losses in wheat production. In wheat many major leaf rust
      resistance genes have been overcome by virulent races. In contrast, the
      prehaustorial resistance (phr) against wheat leaf rust detected in the diploid
      wheat Einkorn (Triticum monoccocum var. monococcum) accession PI272560 confers
      race-independent resistance against isolates virulent on accessions harboring
      resistance genes located on the A-genome of Triticum aestivum. Phr in PI272560
      leads to abortion of fungal development during the formation of haustorial mother
      cells and to increased hydrogen peroxide concentration in comparison to the
      susceptible accession 36554 (Triticum boeoticum ssp. thaoudar var. reuteri).
      Increased peroxidase and endochitinase activity was detected in PI272560 within 6
      h after inoculation (hai). Comparative transcriptome profiling using Massive
      Analysis of cDNA Ends (MACE) in infected and non-infected leaves detected 14220
      differentially expressed tags in PI272560 and 15472 in accession 36554. Of these
      2908 and 3004, respectively, could be assigned to Gene Ontology (GO) categories
      of which 463 were detected in both accessions and 311 were differentially
      expressed between the accessions. In accordance with the concept of non-host
      resistance in PI272560, genes with similarity to peroxidases, chitinases, beta
      1,3-glucanases and other pathogenesis-related genes were up-regulated within the
      first 8 hai, whereas up-regulation of such genes was delayed in 36554. Moreover,
      a Phosphoribulokinase gene contributing to non-host resistance in rice against
      stripe rust was exclusively expressed in the resistant accession PI272560. Gene
      expression underpinned physiological and phenotypic observations at the site of
      infection and are in accordance with the concept of non-host resistance.

PMID- 27881990
TI  - Allometric Trajectories and "Stress": A Quantitative Approach.
AB  - The term "stress" is an important but vague term in plant biology. We show
      situations in which thinking in terms of "stress" is profitably replaced by
      quantifying distance from functionally optimal scaling relationships between
      plant parts. These relationships include, for example, the often-cited one
      between leaf area and sapwood area, which presumably reflects mutual dependence
      between sources and sink tissues and which scales positively within individuals
      and across species. These relationships seem to be so basic to plant functioning
      that they are favored by selection across nearly all plant lineages. Within a
      species or population, individuals that are far from the common scaling patterns
      are thus expected to perform negatively. For instance, "too little" leaf area
      (e.g., due to herbivory or disease) per unit of active stem mass would be
      expected to incur to low carbon income per respiratory cost and thus lead to
      lower growth. We present a framework that allows quantitative study of phenomena
      traditionally assigned to "stress," without need for recourse to this term. Our
      approach contrasts with traditional approaches for studying "stress," e.g.,
      revealing that small "stressed" plants likely are in fact well suited to local
      conditions. We thus offer a quantitative perspective to the study of phenomena
      often referred to under such terms as "stress," plasticity, adaptation, and
      acclimation.

PMID- 27881989
TI  - The Contrasting Effects of Elevated CO2 on TYLCV Infection of Tomato Genotypes
      with and without the Resistance Gene, Mi-1.2.
AB  - Elevated atmospheric CO2 typically enhances photosynthesis of C3 plants and
      alters primary and secondary metabolites in plant tissue. By modifying the
      defensive signaling pathways in host plants, elevated CO2 could potentially
      affect the interactions between plants, viruses, and insects that vector viruses.
      R gene-mediated resistance in plants represents an efficient and highly specific
      defense against pathogens and herbivorous insects. The current study determined
      the effect of elevated CO2 on tomato plants with and without the nematode
      resistance gene Mi-1.2, which also confers resistance to some sap-sucking insects
      including whitefly, Bemisia tabaci. Furthermore, the subsequent effects of
      elevated CO2 on the performance of the vector whiteflies and the severity of
      Tomato yellow leaf curl virus (TYLCV) were also determined. The results showed
      that elevated CO2 increased the biomass, plant height, and photosynthetic rate of
      both the Moneymaker and the Mi-1.2 genotype. Elevated CO2 decreased TYLCV disease
      incidence and severity for Moneymaker plants but had the opposite effect on Mi
      1.2 plants whether the plants were agroinoculated or inoculated via B. tabaci
      feeding. Elevated CO2 increased the salicylic acid (SA)-dependent signaling
      pathway on Moneymaker plants but decreased the SA-signaling pathway on Mi-1.2
      plants when infected by TYLCV. Elevated CO2 did not significantly affect B.
      tabaci fitness or the ability of viruliferous B. tabaci to transmit virus
      regardless of plant genotype. The results indicate that elevated CO2 increases
      the resistance of Moneymaker plants but decreases the resistance of Mi-1.2 plants
      against TYLCV, whether the plants are agroinoculated or inoculated by the vector.
      Our results suggest that plant genotypes containing the R gene Mi-1.2 will be
      more vulnerable to TYLCV and perhaps to other plant viruses under elevated CO2
      conditions.

PMID- 27881991
TI  - Dissecting Long-Term Adjustments of Photoprotective and Photo-Oxidative Stress
      Acclimation Occurring in Dynamic Light Environments.
AB  - Changes in light intensity directly affect the performance of the photosynthetic
      apparatus. Light energy absorbed in excess of cells' needs leads to production of
      reactive oxygen species and photo-oxidative damage. Excess light in both constant
      and dynamic environments induces photoprotective acclimation in plants. Distinct
      sets of signals and regulatory mechanisms are involved in acclimatory adjustment
      of photoprotection and photosynthesis under constant and dynamic (fluctuating)
      light conditions. We are still far away from drawing a comprehensive picture of
      acclimatory signal transduction pathways, particularly in dynamic environments.
      In this perspective article, we propose the use of Arabidopsis plants that
      produce H2O2 in chloroplasts (GO plants) under atmospheric CO2 levels as a tool
      to study the mechanisms of long-term acclimation to photo-oxidative stress. In
      our opinion there are new avenues to future investigations on acclimatory
      adjustments and signal transduction occurring in plants under dynamic light
      environments.

PMID- 27881994
TI  - Quality of pharmacy services and regulatory compliance.

PMID- 27881992
TI  - Molecular Mapping and QTL for Expression Profiles of Flavonoid Genes in Brassica
      napus.
AB  - Flavonoids are secondary metabolites that are extensively distributed in the
      plant kingdom and contribute to seed coat color formation in rapeseed. To
      decipher the genetic networks underlying flavonoid biosynthesis in rapeseed, we
      constructed a high-density genetic linkage map with 1089 polymorphic loci
      (including 464 SSR loci, 97 RAPD loci, 451 SRAP loci, and 75 IBP loci) using
      recombinant inbred lines (RILs). The map consists of 19 linkage groups and covers
      2775 cM of the B. napus genome with an average distance of 2.54 cM between
      adjacent markers. We then performed expression quantitative trait locus (eQTL)
      analysis to detect transcript-level variation of 18 flavonoid biosynthesis
      pathway genes in the seeds of the 94 RILs. In total, 72 eQTLs were detected and
      found to be distributed among 15 different linkage groups that account for 4.11%
      to 52.70% of the phenotypic variance atrributed to each eQTL. Using a genetical
      genomics approach, four eQTL hotspots together harboring 28 eQTLs associated with
      18 genes were found on chromosomes A03, A09, and C08 and had high levels of
      synteny with genome sequences of A. thaliana and Brassica species. Associated
      with the trans-eQTL hotspots on chromosomes A03, A09, and C08 were 5, 17, and 1
      genes encoding transcription factors, suggesting that these genes have essential
      roles in the flavonoid biosynthesis pathway. Importantly, bZIP25, which is
      expressed specifically in seeds, MYC1, which controls flavonoid biosynthesis, and
      the R2R3-type gene MYB51, which is involved in the synthesis of secondary
      metabolites, were associated with the eQTL hotspots, and these genes might thus
      be involved in different flavonoid biosynthesis pathways in rapeseed. Hence,
      further studies of the functions of these genes will provide insight into the
      regulatory mechanism underlying flavonoid biosynthesis, and lay the foundation
      for elaborating the molecular mechanism of seed coat color formation in B. napus.

PMID- 27881995
TI  - Pattern of initial clinical manifestations of systemic lupus erythematosus in a
      tertiary care hospital.
AB  - OBJECTIVE: To determine the pattern of initial clinical manifestations of
      Systemic Lupus Erythematosus (SLE) and to compare these features with those
      recorded elsewhere in Pakistan. METHODS: This cross-sectional, descriptive study
      was performed in the Department of Rheumatology, Fatima Memorial Hospital,
      Lahore, Pakistan, from November 2015 to January 2016. Sixty one patients of SLE
      diagnosed as per ACR (American College of Rheumatology) 1982 revised criteria,
      were enrolled. The patients were evaluated for the initial clinical
      manifestations of SLE. The information was collected on a specially designed
      proforma and analyzed by using SPSS version 17. RESULTS: Out of 61 patients, 49
      (80.3%) were females and 12 (19.7%) males, showing a female to male ratio of 4:1.
      The mean age of patients was 26.2 +/- 7.9 years. Fatigue was the most common
      presenting feature in 56 (91.8%) patients, followed by joint pains in 55 (90.2%)
      and fever in 54 (88.5%). Renal involvement was found in 46 (75.4%). Comparison of
      these presenting features was made with other studies carried out in Northern
      Pakistan (Islamabad) and in central Punjab (Pakistan). There were statistically
      significant differences in fever, fatigue and arthritis between our patients and
      the other two above mentioned study groups. However, comparison of renal
      manifestations showed significant difference only with Islamabad study, and not
      with previous study from central Punjab. CONCLUSION: In this study, majority of
      patients presented with combination of fatigue, fever, rash and arthritis. Almost
      three-fourth of patients had renal manifestations at initial presentation.
      Therefore, it is important for clinicians to have high index of suspicion for
      SLE, when patients present with above symptoms.

PMID- 27881993
TI  - Transcriptome Analysis and Identification of Genes Associated with Floral
      Transition and Flower Development in Sugar Apple (Annona squamosa L.).
AB  - Sugar apple (Annona squamosa L.) is a semi-deciduous subtropical tree that
      progressively sheds its leaves in the spring. However, little information is
      available on the mechanism involved in flower developmental pattern. To gain a
      global perspective on the floral transition and flower development of sugar
      apple, cDNA libraries were prepared independently from inflorescent meristem and
      three flowering stages. Illumina sequencing generated 107,197,488 high quality
      reads that were assembled into 71,948 unigenes, with an average sequence length
      of 825.40 bp. Among the unigenes, various transcription factor families involved
      in floral transition and flower development were elucidated. Furthermore, a Kyoto
      Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that
      unigenes exhibiting differential expressions were involved in various
      phytohormone signal transduction events and circadian rhythms. In addition, 147
      unigenes exhibiting sequence similarities to known flowering-related genes from
      other plants were differentially expressed during flower development. The
      expression patterns of 20 selected genes were validated using quantitative-PCR.
      The expression data presented in our study is the most comprehensive dataset
      available for sugar apple so far and will serve as a resource for investigating
      the genetics of the flowering process in sugar apple and other Annona species.

PMID- 27881996
TI  - Quality of drug stores: Storage practices & Regulatory compliance in Karachi,
      Pakistan.
AB  - OBJECTIVE: To assess and evaluate the drug storage quality and regulatory
      compliance among privately operated drug stores of Karachi Pakistan. METHODS: A
      cross-sectional survey of drug stores located in Karachi was conducted from May
      to December 2013. A total of 1003 drug stores that were involved in the sales,
      purchase and dispensing of pharmaceutical products were approached by non
      probability purposive sampling technique, and the information was collected using
      a close ended, structured questionnaire. RESULTS: Out of 1003 drug stores
      inspected only 4.1%(n=41) were found compliant to regulatory requirements. Most
      of the stores 74.9%(n=752) were selling general items along with the drugs. Only
      12%(n=124) stores were having qualified person working on the store, out of which
      33% were pharmacist. 47.4%(n=400) of the stores had drug sales license displayed
      in the premises and 33.4%(n=282) of the stores had expired drug sales license.
      11.4%(n=94) stores were found selling vaccines without proper refrigerator and
      only 11.7% stores had the power backup for the refrigerator. Only 40.2%(n=403) of
      stores were protected from direct sunlight and 5.4%(n=54) having air conditioning
      in the premises. CONCLUSION: The regulatory compliance of majority of the drug
      stores operated privately in different areas of Karachi is below standard. Only a
      few drugs stores have adequate facilities to protect the drugs from extreme
      temperature, sunlight and provision of refrigeration. Very few of the drug stores
      carry out drug sales under the supervision of qualified pharmacist. There is a
      dire need to improve the storage practices in the drug stores by complying with
      the regulatory standards/laws as specified by the Drug Regulatory Authority of
      Pakistan.

PMID- 27881997
TI  - Relationship of anthropometric measures with Knee Osteoarthritis in diabetes
      mellitus.
AB  - OBJECTIVE: To determine the frequency of knee osteoarthritis in adult patients
      with Diabetes mellitus and its association with body mass index (BMI) in kg/m2
      and waist circumference (WC). METHODS: This is a cross-sectional comparative
      study at a tertiary hospital based in an industrial area of Karachi. Patient
      population comprised of all adult diabetic subjects. Clinical and demographic
      data was obtained with detailed musculoskeletal examination on all patients. BMI
      and WC were measured as kg/m2 and cm respectively. Data was analyzed on SPSS
      version 15. RESULTS: A total of 413 subjects were recruited. Among them diabetic
      and non-diabetic subjects were 210 and 203 respectively. Mean age of diabetics
      was 50.7+-10.2 years as compared to non-diabetic subjects i.e. 49.5+-10.5 years.
      Proportion of male subjects was 72(34.3%) and 71(35.0) respectively in both
      groups. Mean duration of diabetes was 6.2 years. Frequency of knee osteoarthritis
      (OA) was found to be 52(24.8%) and 54(26.6%) in diabetic and non-diabetic
      respectively. Among the diabetic group 6 (18%) subjects with OA had normal BMI
      (18.5-22.9) whereas 4 (16%) were overweight (BMI 23-24.9) and 41(27.5%) were
      obese(BMI >=25). Near 98% (n=51) of the diabetic patients with OA had high waist
      circumference. Females (n= 42, 31.1%) were more frequent than males (n=9, 16%) in
      the diabetic subjects with OA and a higher WC. CONCLUSION: Both diabetic and non
      diabetic group did not show any difference in the frequency of knee OA. However,
      frequency of knee OA showed a significant difference between overweight and obese
      category of BMI.WC appears as a strong predictor of knee osteoarthritis.

PMID- 27881998
TI  - A comparative study on the effects of MRI- and CT-guided interventional therapies
      on uterine fibroids.
AB  - OBJECTIVE: To compare the effects of MRI- and CT-guided interventional therapies
      on uterine fibroids. METHODS: A total of 280 patients with uterine fibroids who
      were treated in our hospital from August 2008 to February 2014 were selected and
      divided into a treatment group and a control group by random draw (n=140). The
      control group and the treatment group were subjected to CT- and MRI-guided
      interventional therapies for uterine artery embolization. RESULTS: After three
      months of treatment, 94.3% and 92.9% of heavy menstrual bleeding and pelvic
      pressure of the treatment group were relieved respectively, which were similar to
      those of the control group (92.9% and 92.1% respectively) (P>0.05). The two
      groups had similar uterine and fibroid sizes before treatment, which were all
      significantly decreased after treatment (P<0.05) when the treatment group had
      significantly smaller uteri and fibroids than the control group did (P<0.05). The
      serum follicle-stimulating hormone, luteinizing hormone, estradiol levels,
      arterial resistive indices and endometrial thicknesses of the two groups were
      similar before treatment, which were significantly increased after treatment
      (P<0.05). Meanwhile, the values of the two groups became significantly different
      (P<0.05). The treatment group was also significantly less prone to complications
      such as fever, vaginal bleeding and hematuria than the control group after
      treatment (P<0.05). CONCLUSION: Interventional therapy, especially that guided by
      MRI, can be performed accurately and safely by mildly affecting the ovary and by
      promoting the recovery of uterine artery blood flow and endometrial thickness.

PMID- 27881999
TI  - Contraceptive failure with Copper T380A intrauterine device (IUD): A single
      tertiary center experience.
AB  - OBJECTIVE: The objective of this study was to assess the risk factors of
      pregnancy with Copper (Cu)T380A IUD and pregnancy outcomes. METHODS: A
      retrospective study evaluating the risk factors and pregnancy outcomes of 81
      patients who conceived with CuT380A IUD in situ. RESULTS: Four ectopic
      pregnancies and 77 intrauterine pregnancies were detected. Twenty-six pregnancies
      (33.76%, 26/77) were terminated according to maternal desire. Twenty-five
      patients (32.46%, 25/77) whose IUDs were removed constituted the Removed IUD
      Group, and the remaining 26 patients constituted IUD Left in situ Group. Term
      pregnancy rates (76% vs. 20.8%, p=0.002) were significantly higher in the Removed
      IUD Group compared with the IUD Left in situ Group. Abortion rates (16% vs.
      53.84%, p=0.008) were detected significantly higher in the IUD Left in situ
      Group. CONCLUSION: The main result of our study was that pregnancy with CuT380A
      in situ is a significant risk factor for adverse perinatal outcome. Adjusting the
      scheduled follow-ups for checking the IUD seems to be important in order to
      prevent accidental pregnancy.

PMID- 27882000
TI  - Study on risk factors (predisposing factors) for poor diabetes control during
      Hajj (1436/2015) in people with diabetes.
AB  - BACKGROUND AND OBJECTIVE: Each year millions of Muslims perform pilgrimage to
      Makkah, Saudi Arabia. It is particularly stressful during the peak five days,
      when all rituals have to be performed at specific periods of time at different
      sites. Poor diabetes control in people with diabetes predisposes to morbidity and
      increases risk of acute complications. We wanted to see how well their blood
      glucose control was before coming to Hajj and whether they were aware, about self
      management of Diabetes and what were reasons for hospital admissions. METHOD: We
      performed an observational prospective study, based on questionnaire. Sixty one
      patients were enrolled after taking informed consent. Patients included in the
      study were known or newly diagnosed diabetics who were admitted to KAMC between
      1st and 30th Zil'Hajj. RESULTS: Of the total 61 patients, 16 were newly
      diagnosed, (not known diabetic, before), while 45 were known diabetics. Among
      known diabetics, about 77% patients had poor diabetes control on admission, 72%
      did not bring glucometer, about 55% received diabetic education before coming to
      Makkah; 37% were doing SMBG occasionally and only 22% were aware that more
      frequent SMBG required during illness. CONCLUSIONS: Most people in our study
      population suffered from poor glycemic control before coming to Hajj. A
      significant number were unaware of their diagnosis. The most significant risk
      factor in our study was a lack of knowledge about self-management of diabetes and
      Hajj specific management.

PMID- 27882001
TI  - Psychiatric symptoms and pregnancy distress in subsequent pregnancy after
      spontaneous abortion history.
AB  - OBJECTIVES: Spontaneous abortion is one of the most important complications of
      pregnancy with short and long adverse psychological effects on women. This study
      assesses the implications of a spontaneous abortion history has on women's
      psychiatric symptoms and pregnancy distress in subsequent pregnancy less than one
      years after spontaneous abortion. METHODS: A case-control study was conducted on
      pregnant women of Babol city from September 2014 to May 2015. In this study, 100
      pregnant women with spontaneous abortion history during a year ago and 100
      pregnant women without spontaneous abortion history were enrolled. All the
      participants in two groups completed the Symptom Checklist-90-Revised (SCL-90-R),
      and pregnancy Distress Questionnaire (PDQ). RESULTS: Women with spontaneous
      abortion history had significantly higher mean of many subscales of SCL-90
      (depression, anxiety, somatization, obsessive-compulsiveness, interpersonal
      sensitivity, psychoticism, hostility, paranoid, and Global Severity Index) more
      than women without spontaneous abortion history. Also, women with spontaneous
      abortion history had significantly higher mean of two subscales of PDQ concerns
      about birth and the baby, concerns about emotions and relationships) and total
      PDQ more than women without spontaneous abortion history. CONCLUSION: Pregnant
      women with less than a year after spontaneous abortion history are at risk of
      psychiatric symptoms and pregnancy distress more than controls. This study
      supports those implications for planning the post spontaneous abortion
      psychological care for women, especially women who wanted to be pregnant during
      12 month after spontaneous abortion.

PMID- 27882002
TI  - A simple integrated primary health care based model for detection of diabetic
      retinopathy in resource-limited settings in Pakistani population.
AB  - OBJECTIVE: To find out prevalence of Diabetic Retinopathy in general population
      of three districts in Pakistan. METHODS: A community based cross-sectional survey
      was conducted in three large districts of Pakistan namely Rawalpindi in Punjab,
      Peshawar in Khyber Pakhtoonkhwa and Hyderabad in Sindh between January 2013 and
      August 2015. Lady Health Workers identified individuals at high risk for diabetes
      based on pre-defined criteria. High risk population was tested for dysglycemia.
      Fundoscopic evaluation for evidence of DR was performed in all individuals with a
      random blood glucose >190mg/dl. Individuals with the evidence of DR were referred
      to affiliated tertiary care ophthalmology departments. RESULTS: A total of 42,629
      individuals reported at the project sites and 63% (n=26,859) were female. Fifty
      one percent (n=21,989) individuals met high risk criteria. Out of these 21,989
      individuals, dysglycemia was found in 3,869 (17.6%). Fundoscopy showed evidence
      of DR in 1,042 (27%) individuals. Amongst high risk population, dysglycemia was
      significantly more common in females as compared to males. The frequency of DR in
      dysglycemic patients was comparable across both gender groups. CONCLUSION: The
      prevalence of DR in Pakistani population is alarmingly high. This preventable
      cause of blindness is largely undiagnosed in our population and a simple
      integrated model based on primary health care facilities can help identify and
      treat a large population of DR patients.

PMID- 27882003
TI  - Risk factors for deep venous thrombosis of lower limbs in postoperative
      neurosurgical patients.
AB  - OBJECTIVES: To detect the risk factors for deep venous thrombosis (DVT) in
      patients after neurosurgery. METHODS: Three hundred and seventy-six patients
      treated in the department of neurosurgery of our hospital from February 2013 to
      November 2015 were reviewed retrospectively. The clinical data including age,
      gender, hospital stay, operation time, occupation type, hypertension, coronary
      heart disease, diabetes, smoking status, drinking status, postoperative
      exercises, malignant tumor, and postoperative hormone or dehydrating agent were
      collected. RESULTS: In this study, 52 patients were included in the DVT group and
      295 patients in the Non-DVT group. There was significant difference in age,
      hypertension, occupation type, malignant tumors, operation time, smoking status,
      and postoperative exercises between the two groups (p<0.05). However, there was
      no significant difference in gender, drinking status, coronary heart disease,
      diabetes, hospital stay, and postoperative hormone or dehydrating agent (p>0.05).
      In multivariate analysis, age, malignant tumor, hypertension were independent
      risk factors, while physical labour and postoperative exercises were protective
      factor for DVT. CONCLUSION: The postoperative patients with older age, malignant
      tumor or hypertension should be paid high attention to prevent DVT, and
      postoperative exercises should be selected as precautionary measures.

PMID- 27882004
TI  - Efficacy and safety of transepithelial collagen cross linking for progressive
      keratoconus.
AB  - OBJECTIVE: To evaluate the efficacy and safety of transepithelial (TE) collagen
      cross-linking (CXL) in patients with progressive keratoconus (KC). METHODS: This
      Quasi Experimental Study was conducted at PNS Shifa Naval Hospital, Karachi from
      June 2015 to June 2016. Sixty eyes of 32 patients who underwent TE CXL for
      progressive KC from June 2015 to June 2016 were analysed to ascertain efficacy
      and safety of TE CXL procedure. Statistical analysis of the data was done using
      SPSS version 17.0. RESULTS: Twenty eight (87.5%) patients underwent TE CXL
      bilaterally, while 4 (12.5%) underwent unilateral CXL. Mean change in
      astigmatism, Maximum simulated Keratometry value (Kmax), Spherical equivalent
      (SE) and Central Corneal Thickness (CCT) were -0.67+/-0.35D, 1.28+/-0.64D, 
      0.58+/-0.17D and 0.40+/-7.58um respectively, from baseline. Mean gain in lines on
      Snellen's visual acuity chart was 1.13+/-0.83 lines. Changes in astigmatism, Kmax
      and SE were statistically significant (p<0.001), while change in CCT was not
      statistically significant. The procedure had excellent safety profile, with no
      major complication till 6 months follow up period. CONCLUSION: TE CXL is a safe
      and effective procedure with statistically significant reduction in corneal
      astigmatism, Kmax and SE with reasonable gain in Snellen's visual acuity.

PMID- 27882005
TI  - Can blood and semen presepsin levels in males predict pregnancy in couples
      undergoing intra-cytoplasmic sperm injection?
AB  - OBJECTIVE: To determine whether semen and plasma presepsin values measured in men
      with normozoospermia and oligoasthenospermia undergoing invitro-fertilization
      would be helpful in predicting ongoing pregnancy and live birth. METHODS: Group-I
      was defined as patients who had pregnancy after treatment and Group-II comprised
      those with no pregnancy. Semen and blood presepsin values were subsequently
      compared between the groups. Parametric comparisons were performed using
      Student's t-test, and non-parametric comparisons were conducted using the Mann
      Whitney U test. RESULTS: There were 42 patients in Group-I and 72 in Group-II. In
      the context of successful pregnancy and live birth, semen presepsin values were
      statistically significantly higher in Group-I than in Group-II (p= 0.004 and p=
      0.037, respectively). The most appropriate semen presepsin cut-off value for
      predicting both ongoing pregnancy and live birth was calculated as 199 pg/mL.
      Accordingly, their sensitivity was 64.5% to 59.3%, their specificity was 57.0% to
      54.2%, and their positive predictive value was 37.0% to 29.6%, respectively;
      their negative predictive value was 80.4% in both instances. CONCLUSION: Semen
      presepsin values could be a new marker that may enable the prediction of
      successful pregnancy and/or live birth. Its negative predictive values are
      especially high.

PMID- 27882006
TI  - Framingham risk score in impaired glucose tolerant population: A sub analysis of
      Diabetes Prevention and Awareness Program of Pakistan.
AB  - OBJECTIVE: To assess the 10-year risk of coronary artery disease (CAD) in
      subjects with impaired glucose tolerance (IGT) using Framingham risk score.
      METHODS: Data for this study was collected from Diabetes Prevention and Awareness
      Program. Primary prevention team visited different primary health care centers,
      factories, service organizations and offices within Karachi, Pakistan. IGT was
      diagnosed according to World Health Organization criteria after taking informed
      consent. Information regarding social-demography, dietary habits and physical
      activities were obtained by a designed questionnaire on one-to-one based
      interview. Framingham risk score (FRS) was used to assess risk of developing CAD.
      RESULTS: A total of 315 subjects with IGT were recruited for the study. Mean age
      of subjects was 44.1 +/- 9.8 years and mean BMI was 27.3 +/- 5.0 kg/m2. Overall,
      31.4% of the participants were at risk of having CAD. Males were 6.4 times and
      hypertensive subjects were 2.44 times more likely to have CAD in next 10 years.
      CONCLUSION: According to the findings of the study, male and hypertensive IGT
      subjects were more likely to develop CAD in next 10 years. Community based
      awareness programs are needed to educate people regarding healthy lifestyle in
      order to reduce the risk of IGT and CAD.

PMID- 27882007
TI  - Therapeutic effects of sequential chemoradiotherapy with pemetrexed and cisplatin
      on locally advanced laryngeal cancer.
AB  - OBJECTIVE: To explore the therapeutic effects of sequential chemoradiotherapy
      with pemetrexed and cisplatin on locally advanced laryngeal cancer (LALC).
      METHODS: Fifty LALC patients who were treated in our hospital between January
      2010 and January 2012 were selected and randomly divided into an observation
      group and a control group (n=25). The two groups were given conventional
      radiotherapy in the same manner, before which two cycles of chemotherapy were
      performed. The observation group intravenously infused with 500 mg/m2 pemetrexed
      on d1 and 25 mg/m2 cisplatin on d1-3, with 28 days as a cycle. The control group
      was intravenously infused with 25 mg/m2 cisplatin on d1-3 and 400 mg/m2
      fluorouracil, with 28 days as a cycle. The short-term effects and adverse
      reactions of both groups were observed after treatment, and their survival was
      observed by follow-up for five years. RESULTS: The response rate was 84% (21/25)
      in the observation group and 64% (16/25) in the control group, between which the
      difference was statistically significant (P<0.05). The differences in the
      incidence rates of short-term adverse reactions such as grade III-IV
      gastrointestinal reactions and bone marrow suppression were not statistically
      significant between PC regimen (pemetrexed combined with cisplatin) and PF
      regimen (cisplatin combined with fluorouracil) (P>0.05). The incidence of long
      term adverse reactions such as grade III-IV laryngeal edemas, laryngeal cartilage
      inflammation and laryngeal cartilage necrosis showed no significant differences
      between the two groups (P>0.05). The median survival was 3.3 years after PC
      chemotherapy and 2.8 years after PF chemotherapy, between which the difference
      was not statistically significant (P>0.05). The levels of serum tumor markers
      significantly decreased after PC and PF treatments compared with those before
      (P<0.05). CONCLUSION: Combining PC chemotherapy with radiotherapy has
      satisfactory short-term therapeutic effects on LALC, and the resulting adverse
      effects can be tolerated. Therefore, this strategy is worthy of promotion and
      application in clinical practice.

PMID- 27882008
TI  - Increase in activity of Na+, K+-ATPase by Porphyrin compounds as treatment for
      Dysnatremias caused by Diabetes Mellitus.
AB  - OBJECTIVE: The aim of this study was to test the action of Porphyrin compounds,
      Tetraphenylporphine sulfonate (TPPS), 5,10,15,20-Tetrakis (4-sulfonatophenyl)
      porphyrinato Iron(III) Chloride (FeTPPS) and 5,10,15,20-Tetrakis (4
      sulfonatophenyl) porphyrinato Iron(III) nitrosyl Chloride (FeNOTPPS), on Na+, K+ 
      ATPase of cell membrane of erythrocytes. METHODS: Enzymatic assays, measuring the
      amount of inorganic phosphate produced, were used to estimate the activity of
      Na+, K+-ATPase. RESULTS: The results show that Porphyrin compounds exert an
      insulin-like effect on Na+, K+-ATPase. They act by increasing the activity of the
      membrane-bound enzyme. CONCLUSION: All the three Porphyrin compounds increased
      the activity of erythrocyte Na+, K+-ATPase. The exact mechanism of action of
      these compounds is not clear.

PMID- 27882009
TI  - Functional and structural abnormalities of the kidney and urinary tract in
      severely malnourished children - A hospital based study.
AB  - OBJECTIVES: The association of malnutrition and systemic diseases like chronic
      kidney disease (CKD) is well known. Various urinary tract abnormalities may be
      associated with malnutrition. So objective of current study was to determine the
      frequency of functional and structural urinary tract abnormalities in severely
      malnourished children admitted in Nutritional Rehabilitation Unit (NRU) of a
      tertiary care facility, Karachi. METHODS: This descriptive cases series of 78
      children was conducted in NRU from October 2014 - March 2015. All newly admitted
      children aged 2-60 months, diagnosed as Severe Acute Malnutrition (SAM) were
      studied and children with known kidney and urinary tract disorders were excluded.
      Detailed history, examination and investigations like serum creatinine,
      ultrasound kidney and urinary tract in addition to routine tests for SAM, were
      done. A proforma was used to collect demographic data, clinical history, physical
      findings, and radio-imaging and biochemical investigations. Glomerular filtration
      rate (GFR) was calculated using Schwartz equation. Data was analyzed using
      descriptive statistics. RESULTS: Among 78 children, male to female ratio was
      equal. Mean age was 18+/-15.53 months and majority (79.48%) of children were
      below 24 months. Majority (82%) of children with SAM had marasmus whereas 18% had
      edematous malnutrition. Out of 78, 57 (73%) children had either functional
      (80.7%) and or structural (19.3%) abnormalities whereas 21(36.84%) had normal
      functional and structural status. Most common functional abnormality was
      subnormal GFR (<90ml/min/1.73 m2) found in all 46 children. Functional
      abnormities were more common in children below 24 months. Other functional
      disorders were Bartter syndrome, renal tubular acidosis and urinary tract
      infection (UTI) found in two cases each. Common structural abnormalities were
      echogenic kidneys (n=4, 36%), hydronephrosis (n=3, 27%), hypoplastic kidneys
      (n=3, 27%) and calculi (n=1, 9%). Subnormal GFR was also found in all cases with
      structural abnormalities. UTI was observed exclusively in two children among 11
      with structural abnormalities. CONCLUSION: A high frequency of functional
      abnormalities and noticeable proportion of structural abnormalities of urinary
      tract were detected in children with SAM. Current finding suggest that
      multicenter study at national level may be undertaken to generate better data
      about prevalence of renal diseases in SAM.

PMID- 27882010
TI  - Short-term clinical effect of conformal radiotherapy combined with tegafur
      gimeracil oteracil potassium in treating recurrent esophagus cancer.
AB  - OBJECTIVE: To observe clinical effects of three-dimensional conformal
      radiotherapy combined with Tegafur Gimeracil Oteracil Potassium chemotherapy in
      the treatment of patients with recurrent esophagus cancer. METHODS: One hundred
      and twelve senile patients who suffered from esophagus cancer were selected and
      randomly divided into two groups, namely, observation group (56 cases) and
      control group (56 cases). The observation group adopted three-dimensional
      conformal radiotherapy combined with Tegafur Gimeracil Oteracil Potassium
      chemotherapy and the control group adopted three-dimensional conformal
      radiotherapy only. RESULTS: All patients completed the treatment, with good
      compliance. Effective rate of the observation group was 82.1%, which was
      significantly higher than the control group (67.9%), and the difference was
      statistically significant (P<0.05). Main toxic and side effects of patients of
      two groups were radiation esophagitis, gastrointestinal reaction, hematologic
      toxicities and radiative skin reaction. Differences of incidence rates of all
      types of toxic and side effects were not statistically significant (P>0.05). The
      one-year and two-year survival rates of patients of the observation group were
      80.4% and 53.6%, respectively, while the control group was 55.4% and 30.4%;
      differences between two groups were statistically significant (P<0.05).
      CONCLUSION: Three-dimensional conformal radiotherapy combined with Tegafur
      Gimeracil Oteracil Potassium chemotherapy has definite curative effect in
      treating patients with recurrent esophagus cancer and can improve survival rate
      of patients, without increasing adverse reaction.

PMID- 27882011
TI  - Better prognostic marker in ICU - APACHE II, SOFA or SAP II!
AB  - OBJECTIVES: This study was designed to determine the comparative efficacy of
      different scoring system in assessing the prognosis of critically ill patients.
      METHODS: This was a retrospective study conducted in medical intensive care unit
      (MICU) and high dependency unit (HDU) Medical Unit III, Civil Hospital, from
      April 2012 to August 2012. All patients over age 16 years old who have fulfilled
      the criteria for MICU admission were included. Predictive mortality of APACHE II,
      SAP II and SOFA were calculated. Calibration and discrimination were used for
      validity of each scoring model. RESULTS: A total of 96 patients with equal gender
      distribution were enrolled. The average APACHE II score in non-survivors
      (27.97+8.53) was higher than survivors (15.82+8.79) with statistically
      significant p value (<0.001). The average SOFA score in non-survivors (9.68+4.88)
      was higher than survivors (5.63+3.63) with statistically significant p value
      (<0.001). SAP II average score in non-survivors (53.71+19.05) was higher than
      survivors (30.18+16.24) with statistically significant p value (<0.001).
      CONCLUSION: All three tested scoring models (APACHE II, SAP II and SOFA) would be
      accurate enough for a general description of our ICU patients. APACHE II has
      showed better calibration and discrimination power than SAP II and SOFA.

PMID- 27882012
TI  - Individualized supervised resistance training during nebulization in adults with
      cystic fibrosis.
AB  - BACKGROUND & OBJECTIVE: Since dyspnea limits exercise adherence and intensity in
      cystic fibrosis (CF) patients, engaging in resistance training (RT), which causes
      less dyspnea than other exercise modalities, while using nebulizers could not
      only overcome this barrier, but also enhance long-term adaptations to treatment.
      The objective of this study was to examine the effects of RT during nebulization
      on spirometry, anthropometry, chest wall excursion, respiratory muscle strength
      and health-related quality of life (HRQOL). METHODS: Fourteen male and female CF
      patients were assigned to a four-week, 20-minute, 5-day per week proof-of-concept
      RT group (RTG) (n=7) or non-exercising control group (CON) (n=7), with 3 CON
      patients later dropping out of the study. Patients performed whole body exercises
      for 3 sets of 10 reps using resistance bands, since such bands have previously
      demonstrated a greater effect on functional exercise capacity than conventional
      RT in lung patients. RESULTS: The RTG displayed significant (p<=0.05) increases
      in FEV1, FEV1/FVC, latissimusdorsi strength, pectoralis major clavicular portion
      strength, pectoralis major sternocostal portion strength and emotional and
      digestion HRQOL domains, while decreasing pectoralis minor strength on the left
      and social, body image and respiration HRQOL domains. CONCLUSION: This small
      scale proof-of-concept investigation demonstrates the multiple and simultaneous
      benefits of RT during nebulization in CF patients. The improvements in pulmonary
      measures are particularly promising especially since this study only made use of
      a four-week experimental period. This study provides an important alternative,
      time-saving treatment for the CF patient that does not add to the treatment
      burden of CF patients.

PMID- 27882013
TI  - Effect of half adult dose of oral Rifampicin (300mg) in patients with idiopathic
      central serous chorioretinopathy.
AB  - OBJECTIVES: To evaluate the effect of half adult dose of oral Rifampicin on mean
      change in best corrected visual acuity and central macular thickness in patients
      with central serous chorioretinopathy. METHODS: Thirty-eight eyes of 31 patients
      with idiopathic central serous chorioretinopathy (CSCR) were registered. Unaided
      Visual acuity, best corrected visual acuity was documented and detailed slit lamp
      examination along with dilated ophthalmoscopy was performed. All subjects were
      treated with oral Rifampicin 300 mg (half adult dose) daily for 03 months.
      Patients underwent a complete ocular and systemic examination as well as central
      macular thickness (CMT) measurement by optical coherence tomography (OCT) every
      month after starting treatment until four months. Fundus fluorescein angiography
      (FFA) was performed in recurrent cases. Liver function tests were carried out
      prior to the treatment and during follow up period. RESULTS: A total of 38 eyes
      of 31 patients (24 males, 07 females) were included in the study. Mean age of
      patients was 36.16+/-3.19 years (range 30-44). Mean best corrected visual acuity
      (BCVA) before treatment was 0.56+/-0.11 and improved to 0.47+/-0.14 at 04 weeks
      (P<0.001) of treatment. The mean CMT at the time of presentation was 494.39+/
      96.29 um and was decreased to 306.90+/-50.71 um after 04 weeks of treatment
      (P<0.001). The mean induced reduction in CMT was 187.48+/-122 um (P<0.001) while
      that in BCVA 0.41+/-0.16 at 04 weeks of treatment (P<0.001). Liver function tests
      were within normal range before and after the treatment. CONCLUSION: Half adult
      dose rifampicin (300mg) is effective and safe in treatment of central serous
      chorioretinopathy without causing any systemic imbalance.

PMID- 27882014
TI  - Expression of Treg/Th17 cells as well as related cytokines in patients with
      inflammatory bowel disease.
AB  - OBJECTIVE: To investigate the expressions of peripheral regulatory T cells (Treg)
      and T helper cells (Th17) as well as related cytokines in peripheral blood of
      patients with inflammatory bowel disease (IBD). METHODS: One hundred four cases
      of IBD patients admitted in our hospital were selected for this study. One
      hundred cases of people receiving healthy physical examination were included in
      the control group in the corresponding period. The levels of CD4+CD25+Treg and
      Th17 subsets were analyzed in peripheral blood of two groups using flow
      cytometry. The expressions of IL-10, TGF-beta1, IL-17 and IL-23 mRNA and protein
      were detected using real-time fluorescence quantitative PCR and ELISA. RESULTS:
      Compared with the control group, the proportion of Treg in peripheral blood was
      decreased significantly in observation group (P<0.05), the proportion of Th17
      cells was increased significantly (P<0.05), and Treg/Th17 was decreased
      significantly (P<0.05). Compared with the control group, the expressions of IL-10
      and TGF-beta1 mRNA and protein in peripheral blood of patients were significantly
      down-regulated in observation group, while the expressions of Th17 cytokines IL
      17 and IL-23 mRNA and protein were significantly increased (P<0.05). CONCLUSION:
      The proportion of Th17 and increased cytokine level suggested the inflammatory
      level was higher in IBD patients. The down regulations of Treg and cytokine
      suggested that the immunosuppression function was down-regulated in IBD patients,
      and the disproportionality might be one of the mechanisms of IBD.

PMID- 27882015
TI  - Are serum eosinophilic cationic protein levels of toll collectors affected by
      diesel exhaust exposure?
AB  - OBJECTIVE: There are few studies on the diesel exhaust particulates (DEP) /
      eosinophilic cationic protein (ECP) level relationship. This study aimed to
      detect ECP levels in a highly DE exposed group, named as toll collectors.
      METHODS: In a cross-sectional study, levels of serum ECP, rates of respiratory
      symptoms, mean levels of respiratory functions, smoking status, and variations in
      peak expiratory flow (PEF) during weekends and working days were compared for 68
      toll collectors (TC) (range of age, 24-48 years) and 28 controls (range of age,
      25-61 years). All subjects in the study group were men. RESULTS: No significant
      difference was observed in terms of symptoms and smoking rates between the toll
      collectors and control group. The number of toll collectors [12/68 (17.7%) vs
      1/28 (3.5%)] with diurnal PEF variability in the working period was higher than
      that of controls (p=0.058). Mean ECP level of toll collectors was higher than
      that of controls (32.8 vs 21.4 ng/L), but the difference was not significant.
      Mean ECP levels were higher in subjects experiencing diurnal PEF variability
      during work and off-work periods (34.9 vs 28.3 ng/L, p=0.410). CONCLUSIONS:
      Serial PEF measurements combined with serum ECP measurements did not add a new
      tool to detect the sensitivity of workers dealing with DE. Much more diesel
      exhaust exposed workers should be included to search for cheap and available
      methods when evaluating airway.

PMID- 27882016
TI  - Sacrohysteropexy performed as uterus conserving surgery for pelvic organ
      prolapse: Review of case files.
AB  - OBJECTIVE: To assess the outcome and safety of sacrohysteropexy as uterus
      conserving surgery for pelvic organ prolapse in young women and to assess
      patients' satisfaction with the procedure. METHODS: This is a case series of
      patients operated at Sind Government Lyari General Hospital and Civil Hospital
      Karachi, between January, 2007 to October, 2015. Data of the patients who had
      sacrohysteropexy were reviewed. Complications during surgery and post-operative
      period including haemorrhage, visceral injury, paralytic ileus and peritonitis
      were studied. Success of procedure, need of blood transfusion, hospital stay and
      condition on discharge and six weeks follow-up were noted. Data were analyzed
      using SPSS version 16. Mean +/- SD was calculated for numerical, while
      frequencies were computed for categorical variables. RESULTS: Data of 60 patients
      were reviewed. Early post-operative success was 100%. Duration of surgery was
      less than two hours in 57 (95%) patients. Blood loss was negligible in majority
      of cases. Out of all 60 cases, 52 (86.7%) did not suffer any complication. One
      patient had ureteric injury, while one patient sustained bowel injury. Two
      patients had paralytic ileus. Four patients suffered from abdominal wound
      infection. All patients were managed satisfactorily. Mean duration of stay in
      hospital was four days. Upon follow up 96.7% patients were satisfied with results
      of operative procedure. Sixteen (26.7%) patients complained of backache on follow
      up visit. CONCLUSION: This review concludes that sacrohysteropexy was successful
      in all cases in early post-operative period. It is a safe procedure and should be
      considered as an option for the treatment of pelvic organ prolapse in young
      women, in whom uterine conservation is required.

PMID- 27882017
TI  - Clinical effect of peripherally inserted central catheters based on modified
      seldinger technique under guidance of vascular ultrasound.
AB  - OBJECTIVE: To observe and analyze the application effect of ultrasound-guided
      modified Seldinger technique (MST) in Peripherally Inserted Central Catheter
      (PICC) catheterization. METHODS: Two hundred patients treated with PICC
      catheterization from January 2013 to December 2015 were selected and randomly
      divided into two groups, namely, observation group and control group. The
      observation group adopted ultrasound-guided MST for catheterization while the
      control group applied traditional puncture technique for catheterization. Then
      efficacy of catheterization, success rate of catheterization and incidence rates
      of complications were compared between two groups. RESULTS: Various indicators of
      catheterization effects of the observation group were better than those of the
      control group, and the differences were statistically significant (P<0.05); one
      time success rate of puncture and catheterization of the observation group was
      both higher than the control group (P<0.05);. Moreover, the incidence of puncture
      points bleeding, phlebitis and thrombus were all lower than those of the control
      group (P<0.05). CONCLUSION: Implementing PICC catheterization based on ultrasound
      guided modified Seldinger puncture technique can increase success rate of
      puncture, improve the effect of catheterization, lower incidence rate of adverse
      effects of catheterization and improve satisfaction and comfort level of
      patients.

PMID- 27882018
TI  - Role of bevacizumab in the prevention of early postoperative haemorrhage after 25
      gauge microincision vitrectomy surgery.
AB  - OBJECTIVE: To evaluate the effect of preoperative intravitreal bevacizumab
      injection on the incidence of postoperative haemorrhage and visual prognosis, in
      patients undergoing 25-gauge micro incision vitrectomy surgery (MIVS) for
      diabetic vitreous haemorrhage. METHODS: One hundred and twenty two eyes of 122
      patients of diabetic retinopathy of both genders and aged over 18 years, who
      presented with non-resolving vitreous haemorrhage were enrolled for this study.
      All patients received an intravitreal injection of 1.25 mg/0.05 mL bevacizumab
      (Avastin) which was followed one week later by 25-gauge sutureless micro incision
      vitrectomy surgery. Main outcomes measured were best corrected visual acuity
      (BCVA) assessed with logMAR and post-operative vitreous haemorrhage. Follow ups
      were up to six months post-operatively. IBM SPSS 21 was used for data analysis.
      RESULT: A total of 122 patients were included; 78 (63.9%) males and 44 (36.1%)
      females. Mean age at the time of surgery was 51.4 +/- 13.66 years. The mean
      preoperative BCVA was 1.64 +/- 0.427 logMAR which improved to 0.57 +/- 0.253
      logMAR at 12 months post-operatively (p-value < 0.001). Recurrent vitreous
      haemorrhage was seen in four patients (3.28%). one1 week before 25-gauge
      vitrectomy helps to reduce the incidence of early post-vitrectomy haemorrhage in
      diabetic patients.

PMID- 27882019
TI  - Plasma BNP level combined with surgical Apgar score to predict operative major
      cardiac adverse events in malignant obstructive jaundice patients.
AB  - OBJECTIVE: To investigate the predictive effect of major adverse cardiac events
      (MACE) in malignant obstructive jaundice (OJ) patients using plasma brain
      natriuretic peptide (BNP) level and surgical Apgar scoring (SAS) system. METHODS:
      Forty one malignant OJ patients undergoing surgical treatments were studied at a
      single center. Pre-and postoperative plasma BNP level, total bilirubin (TBil) and
      data of cardiac function (HR, CVP, CI, LVEF%) were detected, the SAS was
      calculated during the surgery, the relationship of both plasma BNP level and SAS
      with MACE after surgery was analyzed. RESULTS: Thirteen patients out of 41
      (31.71%) experienced MACE without cardiac death. OJ patients had a higher plasma
      BNP level than baseline before operation (191.61+/-105.76 pg/ml VS 175 pg/ml,
      P<0.05), the cardiac function data was improved (CVP: t=4.761, p=0.000; CI:
      t=3.539, p=0.001; LVEF%: t=3.632, p=0.001) after the operation. Patients with
      lower SAS had increasing incidence of MACE after surgery. CONCLUSION: Malignant
      OJ patients with higher preoperative BNP level and lower surgical Apgar score
      were identified at high risk of MACE after surgery.

PMID- 27882020
TI  - Vision screening in children: Is 7-9 years of age a threshold for visual
      impairment?
AB  - OBJECTIVE: The present study aimed to assess the prevalence of decreased visual
      acuity, strabismus, and spectacle wear in children aged 5 to 13 years. METHODS: A
      cross-sectional study was performed in primary education schools. A total of 1938
      participants, including 940 females (48.5%) and 998 males (51.5%) with a mean age
      8.96 +/- 2.31 (5-13 years old), were screened. The comparisons were performed
      with gender, age, and age groups. The children attended to vision screening were
      assigned to three age groups as 5-6 years, 7-9 years, and 10-13 years. RESULTS:
      The prevalence of the parameters was detected as decreased visual acuity 12.4%,
      strabismus 2.2%, and spectacle wear 6.9%. The prevalence of decreased visual
      acuity was significantly higher in girls and in children aged 7-9 years old (p =
      0.013, p < 0.001). The prevalence of spectacle wear was significantly higher in
      girls and in children aged 7-9 years old (p = 0.019, p < 0.001). There was a
      visual acuity decrease in 33 of 106 (31.1%) children despite wearing own
      spectacle. There was no significant difference among three age groups for
      strabismus. CONCLUSION: Increased prevalence of decreased visual acuity, as well
      as the higher frequency of spectacle wear in children at ages of 7-9 years old
      may point out a threshold for visual impairment.

PMID- 27882021
TI  - Compressive strength and the effect of duration after photo-activation among dual
      cure bulk fill composite core materials.
AB  - OBJECTIVES: To assess compressive strength and effect of duration after
      photoactivation on the compressive strength of different dual cure bulk fill
      composites. METHODS: Seventy-two disc shaped (4x10mm) specimens were prepared
      from three dual cure bulk fill materials, ZirconCore (ZC) (n=24), MulticCore Flow
      (MC) (n=24) and Luxacore Dual (LC) (n=24). Half of the specimens in each material
      were tested for failure loads after one hour [MC1 (n=12), LC1 (n=12) & ZC1
      (n=12)] and the other half in 7 days [MC7 (n=12), LC7 (n=12), ZC7 (n=12)] from
      photo-polymerization using the universal testing machine at a cross-head speed of
      0.5 cm/minutes. Compressive strength was calculated using the formula
      UCS=4f/pid2. Compressive strengths among different groups were compared using
      analysis of variance (ANOVA) and Tukey's multiple comparisons test. RESULTS:
      Maximum and minimum compressive strengths were observed in ZC7 (344.14+/-19.22)
      and LC1 (202.80+/-15.52) groups. Specimens in LC1 [202.80 (15.52)] showed
      significantly lower compressive strength as compared to MC1 [287.06 (15.03)]
      (p<0.01) and ZC1 [276.82 (11.51)] (p<0.01). ZC7 [344.14 (19.22)] specimens showed
      significantly higher (p<0.01) compressive strengths compared to LC7 [324.56
      (19.47)] and MC7 [315.26 (12.36)]. Compressive strengths among all three
      materials were significantly higher (p<0.01) at 7 days as compared to one hour.
      CONCLUSIONS: Bulk fill material with Zr nano-hybrid filler (ZC) showed high
      compressive strength compared to MC and LC. Increasing the post photo-activation
      duration (from one hour to 7 days) significantly improves the compressive
      strengths of dual cure bulk fill material.

PMID- 27882022
TI  - Association of rs1800668 polymorphism in glutathione peroxidase- 1 gene and risk
      of rheumatoid arthritis in Pakistani population.
AB  - OBJECTIVE: To investigate the role of glutathione peroxidase 1 (GPX1) C/T
      polymorphism (rs1800668) in modulating the chances of Rheumatoid arthritis (RA)
      in Pakistani population. METHODS: A total of 400 individuals including 200
      controls and 200 patients of RA, were genotyped. Detection of rs1800668
      polymorphism was carried out using PCR based amplification strategy (allele
      specific). RESULTS: The results for Hardy Weinberg Equilibrium (HWE) indicated
      that the allele frequencies for GPX1 polymorphism were not deviant from HWE in
      whole population under observation. The statistical analysis indicated that
      significant association existed between rs1800668 polymorphism and RA (p<0.01).
      CT genotype increased the risk of RA development by 1.8582 times (OR: 1.8582; 95%
      CI 1.2154 to 2.8409). CC genotype was found to have protective effect against the
      disease development (OR: 0.5133; 95% CI 0.3403 to 0.7742) while TT genotype was
      found to have association with RA development but the risk level was marginal
      (OR: 1.5319; 95% CI 0.6124 to 3.8322). CONCLUSION: The present finding suggests
      the importance of GPX1 C/T polymorphism (rs1800668) in development of RA in
      Pakistani population. The protective role of CC genotype against the development
      of RA in local population was also observed.

PMID- 27882023
TI  - Effects of bisoprolol in combination with trimetazidine on the treatment of heart
      failure and concomitant chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To evaluate the effects of bisoprolol combined with trimetazidine on
      the treatment of heart failure patients having concomitant chronic obstructive
      pulmonary disease (COPD); in comparison with control group treated with standard
      therapy only. METHODS: A total of 120 heart failure patients having concomitant
      COPD were selected and randomly divided into a control group and a treatment
      group according to different treatment methods (n=60). The control group was
      given continuous low flow oxygen inhalation and inotropic agents, and their
      cardiac stress was also reduced. The treatment group was treated with bisoprolol
      fumarate and trimetazidine in addition to treatment for COPD. For all patients,
      blood gas analysis and parameters reflecting cardiac function were measured
      respectively before and after treatment. The respiratory symptoms (cough, sputum,
      polypnea, gasp, dyspnea), limitation of motion (daily life, household duties,
      entertainment, sports), disease impacts (social contact, emotion, anxiety) and
      St. George's Respiratory Questionnaire (SGRQ) total scores were observed using
      SGRQ. RESULTS: The oxygen partial pressure (PaO2) and partial pressure of carbon
      dioxide (PaCO2) of the treatment group after treatment were significantly
      different from those before treatment. After treatment, peak E, E/A and IVEF were
      increased by 41%, 44% and 16% respectively, but peak A, LVPWT/mm and IVST/mm were
      significantly reduced. The differences in the respiratory symptoms, limitation of
      motion, disease impacts and SGRQ total scores were statistically significant
      compared with those before treatment (P<0.05) and those of the control group
      (P<0.05). CONCLUSION: Combining bisoprolol with trimetazidine in the treatment of
      heart failure complicating COPD can effectively improve blood gas indices, left
      ventricular systolic and diastolic functions and the quality of life, thereby
      alleviating clinical symptoms.

PMID- 27882024
TI  - Outcomes of first line chemotherapy in patients with chronic lymphocytic
      leukemia.
AB  - OBJECTIVE: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease in terms
      of survival with and without treatment. Many chemo and immunotherapeutic agents
      are available to treat this indolent disease. Aim of this study was to determine
      the outcomes of patients with chronic lymphocytic leukemia treated with different
      available chemotherapeutic regimens. METHODS: All patients with diagnosis of CLL
      from 2008 to 2013 were included. Data were collected from hospital information
      system. Objective response rate (ORR) in terms of complete or partial response
      (CR, PR), stable or progressive disease (SD, PD), overall survival (OS), and
      progression free survival (PFS) were calculated. RESULTS: Fifty seven patients
      were included; 42 (74%) male and 15 (26%) were female. Patients with Binet stage
      A 10 (18%); B 20 (35%) and C were 27(47%). Median age was 50.9 years. Forty six
      (80%) were treated and 11(20%) remained on watch and wait. Treatment indications
      were B symptoms 14 (30%), symptomatic nodal disease 18(39%), thrombocytopenia
      4(9%), anemia 7(15%) and doubling of lymphocyte count 3 (7%). Chemotherapy
      regimens used were FC in 38 (83%), FCR 5(11%), chlorambucil 2(4%) and CVP in
      1(2%) patient. Twenty two (56%) patients had CR, 13(33%) PR, 3(7.6 %) SD, and
      1(2.5%) had PD. ORR was 89%. Median PFS was 23.1 months and median 3 years OS was
      55%. CONCLUSION: Majority of patients was in a relatively younger age group and
      presented with advanced stage disease requiring treatment. Small number of
      patients received rituximab due to cost. PFS and OS are comparable with published
      literature.

PMID- 27882025
TI  - No inhalation in combination with high frequency ventilation treatment in the
      treatment of neonatal severe respiratory failure.
AB  - OBJECTIVE: To discuss over NO inhalation (iNO) in combination with high frequency
      ventilation treatment in relieving clinical symptoms and respiratory state of
      patients with neonatal severe respiratory failure. METHODS: Ninety newborns with
      severe respiratory failure who received treatment in our hospital were selected
      for this study. They were divided into research group and control group according
      to visiting time. Patients in the control group were given conventional treatment
      in combination with high-frequency oscillatory ventilation, while patients in the
      research group were given iNO for treatment additionally besides the treatment
      the same as the control group. Changes of respiratory function indexes and
      arterial blood gas indexes of patients in the two groups were compared.
      Mechanical ventilation time, time of oxygen therapy and the length of hospital
      stay were recorded. Besides, postoperative outcome and the incidence of
      complications were analyzed. RESULTS: After treatment, the level of PaO2 of both
      groups significantly improved, and respiratory function indexes such as partial
      pressure of carbon dioxide in artery (PaCO2), oxygenation index (OI), fraction of
      inspiration O2 (FiO2) and mean arterial pressure (MAP) decreased (P<0.05); the
      improvement of various indexes of the research group was more obvious than that
      of the control group (P<0.05). Mechanical ventilation time, oxygen therapy time
      and the length of hospital stay of the research group was much shorter than those
      of the control group. The incidence of complications in the two groups had no
      statistically significant difference (P>0.05), but the clinical outcome of the
      research group was better than that of the control group. CONCLUSION: NO
      inhalation in combination with high frequency ventilation for treating neonatal
      severe respiratory failure is effective in improving blood gas index and
      respiratory function, enhance cure rate, and reduce the incidence of
      complications and mortality; hence it is safe and effective and worth clinical
      promotion.

PMID- 27882026
TI  - Reflection of medical error highlighted on media in Turkey: A retrospective
      study.
AB  - OBJECTIVE: This study was performed with the aim of identifying how news on
      medical errors have be transmitted, and how the types, reasons, and conclusions
      of medical errors have been reflected to by the media in Turkey. METHODS: A
      content analysis method was used in the study, and in this context, the data for
      the study was acquired by scanning five newspapers with the top editions on the
      national basis between the years 2012 and 2015 for the news about medical errors.
      Some specific selection criteria was used for the scanning of resulted news, and
      116 news items acquired as a result of all the eliminations. RESULTS: According
      to the results of the study; the vast majority of medical errors (40.5%)
      transmitted by the news resulted from the negligence of the medical staff. The
      medical errors were caused by physicians in the ratio of 74.1%, they most
      commonly occurred in state hospitals (31.9%). Another important result of the
      research was that medical errors resulted in either patient death to a large
      extent (51.7%), or permanent damage and disability to patients (25.0%).
      CONCLUSION: The news concerning medical errors provided information about the
      types, causes, and the results of these medical errors. It also reflected the
      media point of view on the issue. The examination of the content of the medical
      errors reported by the media were important which calls for appropriate
      interventions to avoid and minimize the occurrence of medical errors by improving
      the healthcare delivery system.

PMID- 27882027
TI  - Visual outcome of laser treatment in diabetic macular edema: Study from an Urban
      Diabetes Care Center.
AB  - OBJECTIVE: To determine the visual outcome of laser treatment in clinically
      significant macular edema. METHODS: This interventional and qausi experimental
      study was carried out at Diabetic Association of Pakistan (DAP) during January
      2011 and December 2012. Approval was taken from Research Ethical Committee of
      Isra Postgraduate Institute of Ophthalmology. Records of 925 eyes of 464 patients
      with "Clinical Significant macular edema" (CSME), treated with laser
      photocoagulation were analyzed. Best-corrected visual acuity (BCVA) at the time
      of presentation and at the last follow up, minimum of one year and maximum of 45
      months was recorded and compared. SPSS version 20.0 was used to analyze the data.
      RESULTS: Diabetic retinopathy was found in 20.3% (1777) of 8742 diabetic
      attending DAP Hospital" amongst whom 39.6% (705) had Sight threatening diabetic
      retinopathy. Laser was advised in 96.4% (680) individuals, accepted by 70.5%
      (480) individuals. Amongst 960 eyes of 480 patients who accepted laser, 925 eyes
      had clinically significant macular edema and 35 eyes had PDR who are not included
      in this study. Amongst 925 eyes with CSME, Grid laser was done in 913 eyes (99%)
      and focal laser was done in 12 eyes (1%). After a follow up of 12 to 45 months,
      it was found that best corrected visual acuity had declined in 2.4% (22) eyes,
      stabilized in 67% (619) eyes and improved in 30.7% (284) eyes. One line
      improvement on Snellen's chart was fond in 21.3% (197) eyes, 2 lines in 8% (74)
      eyes, 3 lines in 1.2% (12) eyes and 4 lines in one (0.1%) eye with p-value of
      0.000. CONCLUSION: Laser therapy is an effective treatment in
      stabilizing/improving the vision in diabetic macular edema particularly at those
      centers where only Argon Laser is available and OCF, FFA facilities do not exist.

PMID- 27882028
TI  - Patient-specific depth of endotracheal intubation-from anthropometry to the Touch
      and Read Method.
AB  - OBJECTIVE: Knowledge of accurate airway length (AL) enables safer placement of
      the endotracheal tube (ETT) in the trachea. Our objective was to check the safety
      of a new formula (Touch and Read method) to determine ETT depth. METHODS: AL was
      measured in 176 patients. Patients were divided into a normal group (AL >25 cm in
      men, >23 cm in women) and a risk group (AL <=25 cm in men, <=23cm in women). A
      control test (Conventional method) was performed in which the ETT was secured at
      a depth of 23 cm from the central incisor in men and 21 cm in women. In the
      experimental test (Touch and Read method), the ETT was secured at a depth equal
      to the distance from the angle of the mouth to the epiglottis tip plus 12.5 cm in
      men and 11.5 cm in women. The mean distance from the tube tip to the carina and
      that from the vocal cords to tube cuff were compared between the control and
      experimental tests in each group. RESULTS: The two distances were similar between
      control and experimental tests in the normal group, but differed in the risk
      group (Women: mean distance from tube tip to carina, 1.2 cm and from vocal cords
      to cuff, 2.7 cm [control test]; 1.9 and 2.0 cm, respectively [experimental test].
      Men: 0.7 and 3.5 cm, respectively [control test]; 2.0 and 2.3 cm, respectively
      [experimental test]). CONCLUSION: Touch and Read method enables safer placement
      of the ETT in the trachea than the conventional method in the risk group.

PMID- 27882029
TI  - Effects of comprehensive rehabilitation training in combination with multi-mode
      analgesia on body function recovery after tumor-type knee replacement.
AB  - OBJECTIVE: To discuss the significance of comprehensive rehabilitation training
      combined with multimodal analgesia (MMA) for the early knee function recovery of
      patients with knee bone tumor who underwent prosthesis replacement operation.
      METHODS: Sixty patients with knee bone tumor who underwent prosthesis replacement
      operation were selected and randomly divided into two groups according to
      rehabilitation training and postoperative analgesic methods, namely, observation
      group and control group, 30 cases in each group. The control group was treated
      with symptomatic treatment (drugs were given based on pain before and after
      surgery) and continuous passive motion (CPM) functional training, while the
      observation group was treated with comprehensive rehabilitation training combined
      with MMA. The compliance of patients in the two groups was compared and the first
      time off-bed activity time was recorded. Recovery conditions of wounds were
      observed, and recovery conditions of limb functions after operations were
      evaluated. RESULTS: The compliance of patients in the observation group was
      significantly higher than that in the control group, and the difference was
      statistically significant (P<0.05). The first-time off-bed activity time of
      patients of the observation group was earlier than that of the control group. The
      wound recovery condition of the observation group 7 days after operation was
      better compared to that of the control group, and the difference between two
      groups two weeks after operation was not statistically significant. The Hospital
      for special surgery knee (HSS) score and evaluation result of range of motion
      (ROM) of knees of the observation group were both better than those of the
      control group in different periods after operation, and the differences were
      statistically significant (P<0.05). CONCLUSION: Comprehensive rehabilitation
      training combined with MMA can improve the compliance of patients and help
      patients off bed earlier, and remarkably promote the early recovery of knee
      functions; hence it deserves to be promoted clinically.

PMID- 27882030
TI  - Association between 25-Hydroxy Vitamin D and volumetric breast density via a
      fully automated software VolparaTM in the reproductive age group.
AB  - OBJECTIVE: To determine the association between serum 25 hydroxyvitamin D levels
      and percent breast density among asymptomatic premenopausal women. METHODS:
      Hundred asymptomatic, pre-menopausal women who visited the General Surgery Breast
      Clinic, Patel Hospital, Karachi, Pakistan between 3rd March and 10th November,
      2015 were included in this study. The serum 25 (OH)D and calcium levels were
      measured and mammographic density (MD) was assessed using automated volumetric
      breast density software, Volpara Research (algorithm version 1.5.1, Volpara
      solutions Ltd, Wellington, NZ) on the same day. The volumetric breast density
      (VBD) was categorized as; VG1: 0% - 4.5 %; VG2: 4.6% - 7.5%; VG3: 7.6% - 15.5%
      and VG4 >15.5%. Mean serum 25(OH)D and calcium levels were compared across the
      four volumetric breast density categories. The percent volumetric density was
      also correlated with anthropometric measurements and other related variables.
      RESULTS: No significant difference was found in mean serum 25 (OH)D level across
      the four groups (15.87 Vs. 12.40 Vs. 8.99 Vs. 9.68; p-value = 0.106). The percent
      VBD were found significantly negatively correlated with age (r = - 0.365; p-value
      = 0.001), weight (r = - 0.575; p-value = 0.001), height (r = - 0.197; p-value =
      0.049), and BMI (r = - 0.519; p-value = 0.001). The serum Vitamin D, and calcium
      levels were not found significantly correlated with percent VBD (p-value > 0.05).
      CONCLUSION: No significant association exists between serum 25(OH)D level and
      breast density.

PMID- 27882031
TI  - Diagnostic value and disease evaluation significance of abdominal ultrasound
      inspection for neonatal necrotizing enterocolitis.
AB  - OBJECTIVE: To summarize abdominal plain X-rays and ultrasound characteristics of
      144 cases of Neonatal Necrotizing Enterocolitis (NEC) and to analyze diagnostic
      value and disease evaluation significance of abdominal ultrasound inspection for
      NEC. METHODS: Clinical data of 144 NEC patients were retrospectively analyzed
      from February 2014 to December 2015. The patients were divided into suspected NEC
      group (N=74) and confirmed NEC group (N=70) according to amended Bell-NEC
      classification and diagnostic criteria. Meanwhile, we divided them into internal
      medicine treatment group (N=95) and surgery/death group (N=49) according to
      clinical prognosis and took records of their clinical manifestations, laboratory
      inspection results and abdominal plain X-rays and ultrasound characteristics.
      RESULTS: For confirmed NEC group, the detection rate of portal venous gas (PVG)
      and dilatation of intestine by abdominal ultrasound was obviously higher than by
      plain X-rays (P<0.05). Abdominal ultrasound inspection revealed that the
      incidence rate of dilatation of intestine, bowel wall thickening and ascites
      (acoustic transmission difference) of the surgery/death group was higher than
      that of the internal medicine treatment group by comparing risk ratio (RR) and
      95% confidence interval (CI) of RR; the difference was statistically significant
      (P<0.05). The abdominal plain X-rays inspection only showed the result that
      dilatation of intestine and free intraperitoneal air was more often found in the
      surgery/death group (P<0.05). CONCLUSION: Compared with abdominal plain X-rays,
      abdominal ultrasound has certain clinical value and offers more advantages in
      some aspects; therefore, it can be considered as the reference index in
      prediction of clinical prognosis.

PMID- 27882032
TI  - Effect of socio-cultural factors on spontaneous abortion in Burdur, Turkey: A
      population based case-control study.
AB  - OBJECTIVE: To determine the sociocultural factors that have effect on spontaneous
      abortion in Burdur, Turkey. METHODS: Study was designed as case-control study.
      The case group consist of 257 women whose pregnancies ended with spontaneous
      abortion. The control group consisted of 514 women whose pregnancy continued
      since 22 weeks and more during the study. Chi-square, and backward LR logistic
      regression were utilized in analyses. RESULTS: In multifactorial-analyses it was
      determined that four factors (educational status of women, employment status of
      women, exposure to physical violence and non-receipt of ANC) created independent
      risk on spontaneous abortions. CONCLUSIONS: Pregnant women with these risk
      factors should be followed up more frequently and in a more qualified way in
      primary and secondary and tertiary health institutions.

PMID- 27882033
TI  - Comparison of parameters of bone profile and homocysteine in physically active
      and non-active postmenopausal females.
AB  - BACKGROUND AND OBJECTIVES: Optimal physical activity is important in attaining a
      peak bone mass. Physically active women have better bone mineral density and
      reduce fracture risk as compared to females living a sedentary life. The
      objective of this study was to compare parameters of bone profile and serum
      homocysteine levels in physically active and non-active postmenopausal females.
      METHODS: In this cross sectional study postmenopausal females between 50-70 years
      of age were recruited and divided into two groups: Physically inactive (n=133)
      performing light physical activity and Physically active (n=34) performing
      moderate physical activity. Physical activity (in metabolic equivalents), bone
      mineral density and serum homocysteine levels were assessed. Spearman's rho
      correlation was applied to observe correlations. Two independent sample t test
      and Mann Whitney U test were applied to compare groups. P-value <= 0.05 was taken
      statistically significant. RESULTS: Parameters of bone profile were significantly
      higher and serum homocysteine levels were significantly lower in postmenopausal
      females performing moderate physical activity as compared to females performing
      light physical activity. Homocysteine was not significantly related to T-score
      and Z-score in both groups. CONCLUSION: Improving physical activity could be
      beneficial for improving the quality of bone, decreasing fracture risk and
      decreasing serum homocysteine levels.

PMID- 27882034
TI  - Therapeutic effects of mifepristone combined with Gestrinone on patients with
      endometriosis.
AB  - OBJECTIVE: To evaluate the clinical therapeutic effects of mifepristone combined
      with gestrinone on patients with endometriosis. METHODS: A total of 150
      endometriotic patients treated in our hospital between January 2014 and December
      2015 were randomly divided into a control group and a treatment group (n=75). The
      control group began to orally take gestrinone capsules on the second day after
      menstruation started (2.5 mg/time, twice/week). The treatment group orally took
      mifepristone tablets (12.5 mg/time, once/day), and the dosage and administration
      of gestrinone capsules were the same as those of the control group. After 24
      weeks of consecutive treatment, the clinical therapeutic effects of the two
      groups were assessed, and the pelvic symptom score, clinical sign score, serum
      sex hormone levels and pregnancy outcomes were compared. RESULTS: The total
      effective rates of control and treatment groups were 77.3% and 90.7%
      respectively, between which the difference was statistically significant
      (P<0.05). After treatment, the scores of pelvic symptoms (dysmenorrhea,
      dyspareunia, pelvic pain) and clinical signs (pelvic tenderness, induration)
      significantly reduced (P<0.05). Each score of the treatment group decreased more
      significantly than that of the control group did (P<0.05). The serum follicle
      hormone, luteinizing hormone, estrogen and progesterone levels were significantly
      lower than those before treatment (P<0.05). Each level of the treatment group
      dropped more significantly than that of the control group did (P<0.05). The
      pregnancy rates in the 6th and 12th months of follow-up were 28.0% and 13.3% in
      the control group respectively, and 42.7% and 29.3% in the treatment group
      respectively. Such rates of the two groups were significantly different at each
      follow-up time point (P<0.05). CONCLUSION: Mifepristone combined with gestrinone
      had satisfactory clinical therapeutic effects on endometriosis by reducing
      hormone levels and improving pregnancy outcomes. Therefore, this regimen is
      worthy of promotion and application in clinical practice.

PMID- 27882035
TI  - Problem solving, loneliness, depression levels and associated factors in high
      school adolescents.
AB  - OBJECTIVES: To determine problem solving, loneliness, depression levels and
      associated factors in high school adolescents. METHODS: This cross-sectional
      study was conducted in a city west of Turkey (Bursa) in a public high school and
      the population was 774 and the sampling was 394 students. Students to be included
      in the study were selected using the multiple sampling method. A personal
      Information Form with 23 questions, Problem Solving Inventory (PSI), Loneliness
      Scale (UCLA), Beck Depression Inventory (BDI) were used as data collection tools
      in the study. Basic statistical analyses, t-test, Kruskall Wallis-H, One Way
      Anova and Pearson Correlation test were used to evaluate the data. Necessary
      permissions were obtained from the relevant institution, students, parents and
      the ethical committee. RESULTS: The study found significant differences between
      "problem solving level" and family type, health assessment, life quality and
      mothers', fathers' siblings' closeness level; between "loneliness level" and
      gender, family income, health assessment, life quality and mothers', fathers',
      siblings' closeness level; between "depression level" and life quality, family
      income, fathers' closeness level. CONCLUSION: Unfavorable socio-economic and
      cultural conditions can have an effect on the problem solving, loneliness and
      depression levels of adolescents. Providing structured education to adolescents
      at risk under school mental health nursing practices is recommended.

PMID- 27882036
TI  - Molecular epidemiology and clinical features of Hepatitis C Virus (HCV) in
      epidemic areas of Interior Sindh, Pakistan.
AB  - OBJECTIVE: Highly variable genome of HCV and high prevalence in many geographical
      areas made it necessary to conduct local population studies. This study has been
      conducted to show HCV parameters along with clinical features in the local
      population of interior Sindh, province of Pakistan. METHODS: Present study was
      conducted in from August 2010 to November 2015 in the rural areas of Sindh,
      Pakistan. All the 31560 screened samples selected for the study were tested by
      second Generation Enzyme Linked Immunosorbent Assay (ELISA Biokit 480&96).
      RESULTS: Total 31560 people were screened for HCV and out of these 13.67% (n=
      4314) HCV infected patients. When 4314 samples of patients were examined; the
      anti-HCV was significantly higher in males 2814 (14.98%) than in females 1500
      (11.74%) with P value = 0.06. The age of the patients ranged from 18 to 65 years.
      Out of 4314 HCV samples, 3020 (70%) were of Genotype 3a, 237(5.5%) of Genotype
      2a, 108 (2.5%) of Genotype- 1a, 216 (5%) of Genotype 1b, 237 (5.5%) of Genotype
      3b and 43 (1%) of Genotype 4. Additionally, 108 (2.5%) had co-infection and 345
      (8%) samples showed no result -designated as untypable by the genotyping.
      CONCLUSION: This study showed that HCV is most frequently reported disease with
      genotype 3a being the most prevalent genotype.

PMID- 27882037
TI  - Uniportal video-assisted thoracoscopic lobectomy: An alternative surgical method
      for pulmonary carcinoma.
AB  - OBJECTIVES: To explore the effects and feasibility of single-port video-assisted
      thoracic surgery (VATS) on lobectomy for pulmonary carcinoma. METHODS: A total of
      67 patients were enrolled in this study, in which 21 patients were treated by
      single-port VATS (Sing-port Group) and 46 patients by double-port VATS (Double
      port Group). Blood loss, duration of thoracic drainage, length of post-operative
      hospital stay and post-operative pain ratings were compared between the two
      groups. RESULTS: No significant difference existed in blood loss, duration of
      thoracic drainage and length of postoperative hospital stay between the two
      groups. However, Post-operative pain was significantly reduced in Single-port
      Group compared to Double-port Group. CONCLUSION: Single-port VATS was totally
      feasible with reduced post-operative pain and good looking appearance.

PMID- 27882038
TI  - Alzheimer and vascular dementia in the elderly patients.
AB  - OBJECTIVES: To find out the frequency of Alzheimer's and Vascular dementia in the
      elderly patients. METHODS: This cross sectional descriptive study was conducted
      in Department of Medicine, Ziauddin Hospital Karachi from 1st October 2013 to
      31st March 2014. Patients with symptoms of dementia for more than 6 months
      duration, and Mini Mental State Examination score <24 were included in this
      study. Patients who fell in category of dementia were assessed for duration of
      symptoms. Patients underwent CT scan of brain. Patients with generalized atrophy
      of brain on CT scanning of brain were labeled as Alzheimer's dementia, while
      patients with ischemic or hemorrhagic stroke on CT scan of brain were labeled as
      vascular dementia. RESULTS: Four hundred twenty two patients were included in
      this study. There were 232 (54.98 %) male and 190 (45.02 %) were female. The mean
      age +/- SD of the patients was 72.58+/-5.34 years (95% CI: 72.07 to 73.09),
      similarly average duration of symptoms was 10.14+/-2.85 months. About 18.96% of
      patients were illiterate, 32.23% were matric, 28.44% were intermediate and 20.33%
      were graduate and post graduate. Hypertension and diabetes were the commonest co
      morbid i.e. 81.3% and 73.7%, hyperlipedimia and smoking were 38.2% and 45%
      respectively. Frequency of Alzheimer's disease and vascular dementia in the
      elderly was observed in 3.79% (16/422) and 2.61% (11/422) cases. CONCLUSION: A
      good number of patients, 27 out of 422, in this hospital based study were
      suffering from Alzheimer's disease and vascular dementia. Early detection and
      prompt treatment can reduce the burden of the disease in our population.

PMID- 27882040
TI  - A New Model of Master of Philosophy in Physiological Sciences.
AB  - The objectives of Master of Philosophy (MPhil) in Physiological Sciences are: 1)
      to describe the new ways in which anatomy, biochemistry and physiology on one
      hand, and microbiology, pathology and pharmacology on other hand meet their
      functional requirements through multidisciplinary integrated concepts; 2) to
      elucidate relationships between cell biology, molecular biology and molecular
      genetics by connecting dots of how cell functions are driven by molecules and
      being controlled by genes. This forms the basis of cell, molecular and genetics
      [CMG] module upon which 7 multidisciplinary modules of Physiological Sciences
      follow; 3) these 24 credit hours provide the physiological basis for PhD studies
      as well as faculty development to enhance learning abilities of medical student;
      4) the modules constitute Cardio- Respiratory Physiological Sciences, GI and
      Renal Physiological Sciences, Neurosciences, Endo-Reproductive Physiological
      Sciences.; 5) it has integrated microbiology, pathology and pharmacology in a
      unique way through CMG of microbes leading to associated pathology and mechanisms
      of prescribed drugs; 6) it has additional synopsis and thesis friendly course
      work leading to comprehensive examinations; 7) the year two deals with research
      work of 6 credit hours leading to defense of thesis; 8) The MPhil in
      Physiological Sciences is fundamentally different from what is being offered
      elsewhere. It prepares and offers a good spring board to dovetail PhD studies as
      well as faculty and institutional development. This is the first study that deals
      with innovative programmes in research, learning and education in the field of
      physiological sciences. This broad-based MPhil would make its recipients
      competent, critical, confident and productive learner. This is a completely
      unique design of a curriculum that has no comparable examples elsewhere. Our
      mission is to educate graduate students in the field of Physiological Sciences
      such that they have a complete grasp over the broad-based integrated concepts of
      basic health sciences. Upon completion of their education, the students will be
      able to use the duality of imagination and skepticism. Hence, the students will
      contribute to their fields by unfolding their creative energy.

PMID- 27882039
TI  - Pediatric tooth extractions under sedoanalgesia.
AB  - OBJECTIVE: The present study aims to evaluate intravenous ketamine and inhalation
      sedation in children, their unwanted side-effects and surgeon satisfaction.
      METHODS: In this study, data of 922 children aged between 1-18 who underwent
      tooth extraction under sedoanalgesia in our department between September 2015
      January 2016 were gathered and anesthesia approaches, unwanted side effects and
      surgical satisfaction was investigated. Postoperative recovery emergence
      agitation or delirium was evaluated with Watcha Behavior Scale (WBS). RESULTS:
      Patients were grouped and compared according to acceptance of intravenous line
      placement (Group-1) or not (Group- 2). Group 1 received intravenous ketamine
      anesthesia (n=822), Group 2 received inhalation anesthesia with sevoflurane
      (n=100). Number of patients, age, weight and gender was significantly different
      in two groups. When side effects were investigated nausea was observed in 30
      patients (3.6%), skin rashes were observed in 26 patients (3.2%) in Group-1 while
      skin rashes were observed in one patient (1%) in Group 2. 95% of surgeons
      reported intravenous anesthesia, 18% of surgeons reported inhalation anesthesia
      to be the anesthesia of choice. Emergence of postoperative recovery agitation
      (WBS>=3) was observed more frequent in Group 2 (p<0.05) than Group 1. CONCLUSION:
      Ketamine, which has analgesic, hypnotic and amnestic effects and which does not
      alter pharyngeal and laryngeal reflexes thus minimizes aspiration possibility, is
      a safe and effective anesthetic agent for tooth extractions of the pediatric
      population under sedoanalgesia.

PMID- 27882041
TI  - Resolution of pleura-peritoneal fistula via transient daytime ambulatory
      peritoneal dialysis regime (DAPD) - 8 years follow up.
AB  - Pleural effusion or hydrothorax is a relatively rare but well-recognized
      complication associated with peritoneal dialysis (PD). We describe the successful
      long term resolution of a patient who developed pleural effusions after starting
      continuous ambulatory peritoneal dialysis (CAPD), by altering the PD prescription
      to normal volume daytime ambulatory peritoneal dialysis (DAPD) transiently before
      resuming the usual CAPD exchanges four months later. After 8 years of follow up,
      there is no sign of recurrence of the effusion. Normal volume DAPD present as an
      attractive alternative and cheap method for resolution of pleura-peritoneal
      fistula.

PMID- 27882042
TI  - Treatment of persistent congenital chylothorax with intrapleural injection of
      sapylin in infants.
AB  - Test the therapeutic efficacy of Sapylin in resolving persistent Congenital
      Chylothorax (CC) in four infants who failed to respond to conservative medical
      therapy including Erythromycin and/or Octreotide management. All cases were cured
      and have no adverse reactions during follow-up. The result shows Sapylin is
      effective in reducing chylous production.

PMID- 27882043
TI  - Why cannot a beta-lactamase gene be detected using an efficient molecular
      diagnostic method?
AB  - OBJECTIVE: Fast detection of beta-lactamase (bla) genes can minimize the spread
      of antibiotic resistance. Although several molecular diagnostic methods have been
      developed to detect limited bla gene types, these methods have significant
      limitations, such as their failure to detect almost all clinically available bla
      genes. We have evaluated a further refinement of our fast and accurate molecular
      method, developed to overcome these limitations, using clinical isolates.
      METHODS: We have recently developed the efficient large-scale bla detection
      method (large-scaleblaFinder) that can detect bla gene types including almost all
      clinically available 1,352 bla genes with perfect specificity and sensitivity.
      Using this method, we have evaluated a further refinement of this method using
      clinical isolates provided by International Health Management Associates, Inc.
      (Schaumburg, Illinois, USA). Results were interpreted in a blinded manner by
      researchers who did not know any information on bla genes harbored by these
      isolates. RESULTS: With only one exception, the large-scaleblaFinder detected all
      bla genes identified by the provider using microarray and multiplex PCR. In one
      of the Escherichia coli test isolates, a blaDHA-1 gene was detected using the
      multiplex PCR assay but it was not detected using the large-scaleblaFinder.
      CONCLUSION: The truncation of a blaDHA-1 gene is an important reason for an
      efficient molecular diagnostic method (large-scaleblaFinder) not to detect the
      bla gene.

PMID- 27882044
TI  - The importance of rehabilitation concerning upper extremity amputees: A
      Systematic review.
AB  - OBJECTIVE: To evaluate and point out the importance of prosthetic rehabilitation
      of upper extremity. METHODS: A systematic literature search was performed to
      identify studies concerning prosthetic rehabilitation in upper extremity. The
      PRISMA Statement 2009 was used to establish the study and the methodological
      quality was assessed. RESULTS: The literature search identified 620 studies. Of
      these 620, 9 studies fulfilled the inclusion criteria and were included for data
      extraction. The studies pointed out the upper limb prosthetic rehabilitation
      protocols consist of general exercise programme, motor tasks, phantom exercises,
      Muscle Training System, edema control, functional activities, signal
      strengthening, prosthetic education exercises, neuromuscular reeducation, virtual
      image and virtual reality exercises. CONCLUSIONS: The current systematic
      literature review has shown that the prosthetic rehabilitation seems promising
      especially for upper extremity amputees.

PMID- 27882045
TI  - Comparison of BISAP, Ranson, MCTSI, and APACHE II in Predicting Severity and
      Prognoses of Hyperlipidemic Acute Pancreatitis in Chinese Patients.
AB  - In recent years, with the developing of living standard, hyperlipidemia becomes
      the second major reason of acute pancreatitis. It is important to predict the
      severity and prognosis at early stage of hyperlipidemic acute pancreatitis
      (HLAP). We compared the BISAP, Ranson, MCTSI, and APACHE II scoring system in
      predicting MSAP and SAP, local complications, and mortality of HLAP. A total of
      326 diagnosed hyperlipidemic acute pancreatitis patients from August 2006 to July
      2015 were studied retrospectively. Our result showed that all four scoring
      systems can be used to predict the severity, local complications, and mortality
      of HLAP. Ranson did not have significant advantage in predicting severity and
      prognosis of HLAP compared to other three scoring systems. APACHE II was the best
      in predicting severity of HLAP, but it had shortcoming in predicting local
      complications. MCTSI had outstanding performance in predicting local
      complications, but it was poor in predicting severity and mortality. BISAP score
      had high accuracy in assessment of severity, local complications, and mortality
      of HLAP, but the accuracy still needs to be improved in the future.

PMID- 27882047
TI  - Perioperative Elevation in Cell-Free DNA Levels in Patients Undergoing Cardiac
      Surgery: Possible Contribution of Neutrophil Extracellular Traps to Perioperative
      Renal Dysfunction.
AB  - Background. This study aimed to determine the perioperative change in serum
      double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil
      extracellular trap concentration in samples from patients undergoing cardiac
      surgery and to analyze a relationship between serum dsDNA concentrations and
      perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples
      that were collected during a previously conducted, prospective, multicenter,
      observational study were measured. Eighty patients undergoing elective cardiac
      surgery were studied. Serum samples were collected at baseline, immediately after
      surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration
      was significantly increased from baseline (median, 398 ng/mL [interquartile
      range, 372-475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437-682
      ng/mL], p < 0.001), and they were reduced by POD-1 (median, 323 ng/mL [256-436
      ng/mL]). The difference in serum creatinine concentration between baseline and
      POD-1 was correlated with dsDNA concentration on POD-1 (rs = 0.61, p < 0.001).
      Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is
      elevated postoperatively. Prolonged elevation in dsDNA concentration is
      correlated with perioperative renal dysfunction. Further large-scale studies are
      needed to determine the relationship between serum concentration of circulating
      dsDNA and perioperative renal dysfunction.

PMID- 27882046
TI  - The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing
      Cholangitis in Childhood.
AB  - Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease
      characterized by chronic inflammation of the biliary tree resulting in liver
      fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of
      PSC is based on clinical, laboratory, image, and histological findings. A
      biochemical profile of mild to severe chronic cholestasis can be observed.
      Endoscopic retrograde cholangiography is the golden standard method for
      diagnosis, but magnetic resonance cholangiography is currently also considered a
      first-line method of investigation. Differences in clinical and laboratory
      findings were observed in young patients, including higher incidence of overlap
      syndromes, mostly with autoimmune hepatitis, higher serum levels of
      aminotransferases and gamma-glutamyl transferase, and lower incidence of serious
      complications as cholangiocarcinoma. In spite of the detection of several HLA
      variants as associated factors in large multicenter cohorts of adult patients,
      the exact role and pathways of these susceptibility genes remain to be determined
      in pediatric population. In addition, the literature supports a role for an
      altered immune response to pathogens in the pathogenesis of PSC. This phenomenon
      contributes to abnormal immune system activation and perpetuation of the
      inflammatory process. In this article, we review the role of immune and genetic
      factors in the pathogenesis of PSC in pediatric patients.

PMID- 27882049
TI  - Different Effects of Myoinositol plus Folic Acid versus Combined Oral Treatment
      on Androgen Levels in PCOS Women.
AB  - Recently, myoinositol (myo-ins) and folic acid combination has gained an
      important role for treating Polycystic Ovary Syndrome (PCOS), in addition to
      combined oral contraceptives (COC). We aimed to examine myo-ins effects on anti
      Mullerian hormone (AMH) levels and compare them with those ones obtained
      administering COC. In this prospective study, 137 PCOS patients, diagnosed
      according to Rotterdam criteria and admitted to the Reproductive Endocrinology
      and Infertility Outpatient Clinic at Dokuz Eylul University (Izmir, Turkey), were
      included. After randomization to COC (n = 60) and myo-ins (n = 77) arms,
      anthropometric measurements, blood pressure, Modified Ferriman Gallwey scores
      were calculated. Biochemical and hormonal analysis were performed, and LH/FSH and
      Apo B/A1 ratios were calculated. Data analysis was carried out in demographically
      and clinically matched 106 patients (COC = 54; myo-ins = 52). After 3-month
      treatment, increase in HDL and decreases in LH and LH/FSH ratio were
      statistically more significant only in COC group when compared with baseline (in
      both cases p > 0.05). In myo-ins group, fasting glucose, LDL, DHEAS, total
      cholesterol, and prolactin levels decreased significantly (for all p < 0.05).
      Progesterone and AMH levels, ovarian volume, ovarian antral follicle, and total
      antral follicle counts lessened significantly in both groups (for all p < 0.05).
      In PCOS treatment, MYO is observed more effective in reductions of total ovarian
      volume and AMH levels.

PMID- 27882048
TI  - Pattern and Epidemiology of Poisoning in the East African Region: A Literature
      Review.
AB  - The establishment and strengthening of poisons centres was identified as a
      regional priority at the first African regional meeting on the Strategic Approach
      to International Chemicals Management (SAICM) in June 2006. At this meeting, the
      possibility of a subregional poisons centre, that is, a centre in one country
      serving multiple countries, was suggested. The WHO Headquarters following
      consultation with counterparts at the WHO Regional Office for Africa (AFRO) and
      the SAICM Africa Regional Focal Point successfully submitted a proposal to the
      SAICM Quick Start Programme (QSP) Trust Fund Committee for a feasibility study
      into a subregional poisons centre in the Eastern Africa subregion. However,
      before such a study could be conducted it was deemed necessary to carry out a
      literature review on the patterns and epidemiology of poisoning in this region so
      as to inform the feasibility study. The current paper presents the results of
      this literature review. The literature search was done in the months of June and
      July 2012 by two independent reviewers with no language or publication date
      restrictions using defined search terms on PUBMED. After screening, the eventual
      selection of articles for review and inclusion in this study was done by a third
      reviewer.

PMID- 27882050
TI  - Thyroid Stimulating Hormone Is Increased in Hypertensive Patients with
      Obstructive Sleep Apnea.
AB  - Purpose. To evaluate alteration in serum TSH in hypertensives with OSA and its
      relation with cardiometabolic risk factors. Methods. 517 hypertensives were cross
      sectionally studied. OSA was determined by polysomnography and thyroid function
      by standard methods. Results. OSA was diagnosed in 373 hypertensives (72.15%).
      Prevalence of subclinical hypothyroidism was significantly higher in OSA
      hypertensives than in non-OSA ones (15.0% versus 6.9%, P = 0.014). Serum LnTSH in
      hypertensives with severe OSA was significantly higher (0.99 +/- 0.81 versus 0.74
      +/- 0.77 MUIU/mL, P < 0.05) than in those without OSA. AHI, LSaO2, ODI3, and ODI4
      were independently associated with serum TSH for those aged 30-65 years. Dividing
      subjects into four groups as TSH < 1.0 MUIU/mL, 1.0 <= THS <= 1.9 MUIU/mL, 1.91
      <= TSH < 4.5 MUIU/mL, and TSH >= 4.5 MUIU/mL, only 26.3% of OSA subjects
      exhibited TSH between 1.0 and 1.9 MUIU/mL, significantly less than non-OSA
      subjects (26.3% versus 38.2%, P = 0.01). DBP and serum LDL-c elevated with TSH
      increasing and were only significantly higher in TSH >= 4.5 MUIU/mL group than in
      1.0 <= TSH <= 1.9 MUIU/mL group (96.32 +/- 14.19 versus 92.31 +/- 12.86 mmHg; P =
      0.040; 0.99 +/- 0.60 versus 0.87 +/- 0.34 mmol/L, P = 0.023). Conclusion. OSA
      might be a risk factor for increased TSH even within reference range in
      hypertensive population.

PMID- 27882051
TI  - Glycated Hemoglobin Levels in Patients with Decompensated Cirrhosis.
AB  - Introduction. Aim of this study is to determine if HbA1c levels are a reliable
      predictor of glycemic control in patients with decompensated cirrhosis. Methods.
      200 unique patients referred for liver transplantation at University of
      Tennessee/Methodist University Transplant Institute with a HbA1c result were
      included. Three glucose levels prior to the "measured" A1c (MA1c) were input into
      an HbA1c calculator from the American Diabetes Association website to determine
      the "calculated" A1c (CA1c). The differences between MA1c and CA1c levels were
      computed. Patients were divided into three groups: group A, difference of <0.5;
      group B, 0.51-1.5; and group C, >1.5. Results. 97 (49%) patients had hemoglobin
      A1c of less than 5%. Discordance between calculated and measured HbA1c of >0.5%
      was seen in 47% (n = 94). Higher level of discordance of greater than >1.5 was in
      12% of patients (n = 24). Hemoglobin was an independent predictor for higher
      discordance (odds ratio 0.77 95%, CI 0.60-0.99, and p value 0.04). HbA1c was an
      independent predictor of occurrence of HCC (OR 2.69 955, CI 1.38-5.43, and p
      value 0.008). Conclusion. HbA1c is not a reliable predictor of glycemic control
      in patients with decompensated cirrhosis, especially in those with severe anemia.

PMID- 27882052
TI  - Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male
      Children: Preliminary Data.
AB  - Myoinositol and D-chiro inositol, which are inositol isomers, have been shown to
      possess insulin-mimetic properties and to improve insulin resistance, especially
      in women with polycystic ovary syndrome. However, it has not been determined if
      this relationship exists also in children. Based on these previous findings, we
      hypothesized that inositol could be effective in improving insulin sensitivity in
      children with insulin resistance. To evaluate this hypothesis, we administered
      both inositol formulations before carrying out an oral glucose tolerance test
      (OGTT) in a group of obese insulin-resistant male children with high basal
      insulin levels and compared the values obtained with an OGTT previously conducted
      without inositol, in the same group, with unchanged BMI. Our results confirm that
      myoinositol and D-chiro inositol acutely reduce insulin increase after glucose
      intake mainly in children with high basal insulin level.

PMID- 27882053
TI  - Hypoxia-Inducible Factor-1alpha Expression in Indonesian Laryngeal Squamous Cell
      Carcinoma Patients.
AB  - Objectives. This research aimed to determine the association between hypoxia
      inducible factor-1alpha (HIF-1alpha) expression and laryngeal squamous cell
      carcinoma clinical stage. Methods. We retrospectively analyzed paraffin-embedded
      tissue from 47 laryngeal squamous cell carcinoma (LSCC) patients from 2011 to
      2014. HIF-1alpha expression was analyzed by immunohistochemistry using an anti
      HIF-1alpha mouse monoclonal antibody. The association between HIF-1alpha
      expression and clinical stage was analyzed using the chi square test. Results.
      The glottis was the predominant site of laryngeal squamous cell carcinoma
      occurrence, and 43/47 (91.5%) patients presented at an advanced stage. Of the
      advanced stage patients, 27/43 stained positive for HIF-1alpha expression and
      16/43 stained negative. Of the early stage patients, 2/4 stained positive for HIF
      1alpha expression and 2/4 stained negative. Statistical analysis did not
      demonstrate significant association of HIF-1alpha expression. Conclusion. There
      was no statistically significant association between HIF-1alpha expression and
      the clinical stage or histological differentiation of LSCC.

PMID- 27882054
TI  - Risk of Cancer among Commercially Insured HIV-Infected Adults on Antiretroviral
      Therapy.
AB  - The objective of this study was to explore the cancer incidence rates among HIV
      infected persons with commercial insurance who were on antiretroviral therapy and
      compare them with those rates in the general population. Paid health insurance
      claims for 63,221 individuals 18 years or older, with at least one claim with a
      diagnostic code for HIV and at least one filled prescription for an
      antiretroviral medication between January 1, 2006, and September 30, 2012, were
      obtained from the LifeLink(r) Health Plan Claims Database. The expected number of
      cancer cases in the general population for each gender-age group (<30, 30-39, 40
      49, 50-59, and >60 years) was estimated using incidence rates from the
      Surveillance Epidemiology and End Results (SEER) program. Standardized incidence
      ratios (SIRs) were estimated using their 95% confidence intervals (CIs). Compared
      to the general population, incidence rates for HIV-infected adults were elevated
      (SIR, 95% CI) for Kaposi sarcoma (46.08; 38.74-48.94), non-Hodgkin lymphoma
      (4.22; 3.63-4.45), Hodgkin lymphoma (9.83; 7.45-10.84), and anal cancer (30.54;
      25.62-32.46) and lower for colorectal cancer (0.69; 0.52-0.76), lung cancer
      (0.70; 0.54, 0.77), and prostate cancer (0.54; 0.45-0.58). Commercially insured,
      treated HIV-infected adults had elevated rates for infection-related cancers, but
      not for common non-AIDS defining cancers.

PMID- 27882056
TI  - Pediatric Isolated Sinonasal Schwannoma: A New Case Report and Literature Review.
AB  - Schwannomas of the paranasal sinus are uncommon. Less than 4% of schwannomas
      involve the nasal cavity and paranasal sinuses, even less in the pediatric age
      group. A case of schwannoma arising in maxillary sinus in a 2.5-year-old Chinese
      boy is reported. The basis for discussion of this case is the exceptional rarity
      of sinonasal schwannoma in pediatric patients.

PMID- 27882055
TI  - Determinants of Patient Delay in Seeking Diagnosis and Treatment among Moroccan
      Women with Cervical Cancer.
AB  - Introduction. This study sought to investigate potential determinants of patient
      delay among Moroccan women with cervical cancer. Methods. A cross-sectional study
      was conducted from June 2014 to June 2015 at the National Institute of Oncology
      in Rabat. Data were collected using questionnaire among patients with cervical
      cancer locally advanced or metastatic (stages IIA-IVB). Medical records were
      abstracted to complete clinical information. An interval longer than 90 days
      between discovery of initial symptoms and presentation to a provider was defined
      as a patient delay. Results. Four hundred and one patients with cervical cancer
      enrolled in this study. The mean age was 52.4 years (SD = 11.5). 53.6% were
      illiterate. Abnormal vaginal bleeding was identified for 65.8% of patients. 60.1%
      were diagnosed at stages IIA-IIB. 55.4% were found having patient delay. The
      regression analyses showed the association between literacy (p < 0.001), distance
      of the place of the first consultation (p = 0.031), abnormal vaginal bleeding as
      an earlier symptom (p < 0.001), stage at diagnosis (p < 0.03), knowledge of
      symptoms (p < 0.001), knowledge of causes (p = 0.008), and practice of
      gynecological exam during the last three years (p = 0.018) and the patient delay.
      Conclusion. Educational messages should aim at increasing awareness of cervical
      cancer, assisting women in symptom recognition, and encouraging earlier
      presentation.

PMID- 27882057
TI  - Robotic Assisted Laparoscopic Prostatectomy Performed after Previous Suprapubic
      Prostatectomy.
AB  - Operative management of prostate cancer in a patient who has undergone previous
      open suprapubic simple prostatectomy poses a unique surgical challenge. Herein,
      we describe a case of intermediate risk prostate cancer in a man who had
      undergone simple prostatectomy ten years prior to presentation. The patient was
      found to have Gleason 7 prostate cancer on MRI fusion biopsy of the prostate for
      elevated PSA and underwent an uncomplicated robot assisted laparoscopic radical
      prostatectomy.

PMID- 27882059
TI  - Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy.
AB  - Epilepsy is one of the most widespread serious neurological disorders, and an
      aetiological explanation has not been fully identified. In recent decades, a
      growing body of evidence has highlighted the influential role of autoimmune
      mechanisms in the progression of epilepsy. The hygiene hypothesis draws people's
      attention to the association between gut microbes and the onset of multiple
      immune disorders. It is also believed that, in addition to influencing digestive
      system function, symbiotic microbiota can bidirectionally and reversibly impact
      the programming of extraintestinal pathogenic immune responses during
      autoimmunity. Herein, we investigate the concept that the diversity of
      parasitifer sensitivity to commensal microbes and the specific constitution of
      the intestinal microbiota might impact host susceptibility to epilepsy through
      promotion of Th17 cell populations in the central nervous system (CNS).

PMID- 27882061
TI  - The Long-Term Outcomes for Patients with Budd-Chiari Syndrome Caused by Behcet's
      Disease: A Case Series on the Results, from Cirrhosis to Death.
AB  - BACKGROUND: Budd-Chiari syndrome, which is a rare complication of Behcet's
      disease, carries a high mortality rate. OBJECTIVES: The aim of the study was to
      present our long-term follow up experience with patients suffering from Budd
      Chiari syndrome due to Behcet's disease. METHODS: The records of 402 patients
      with Behcet's disease were evaluated retrospectively. To facilitate detection of
      the long-term complications caused by Budd-Chiari syndrome, the patients were
      evaluated via physical examinations, laboratory tests, imaging modalities, and
      endoscopy results. RESULTS: The data for 402 patients diagnosed with Behcet's
      disease, who were followed up at our hospital over 16 years, were analyzed
      retrospectively. Five of these 402 patients (1.2%) were diagnosed as having Budd
      Chiari syndrome. The patients with Budd-Chiari syndrome were aged between 23 and
      54, and all five were male. The interval between the onset of Behcet's disease
      and the development of Budd-Chiari syndrome ranged from 1 to 8 years. All the
      patients had combined venous occlusion (affecting the hepatic vein and inferior
      vena cava). Portal venous thrombosis was detected in only one patient (Case 1),
      who died 1 month after the diagnosis of Budd-Chiari syndrome. The survival time
      for the other four patients after the diagnosis of Budd-Chiari syndrome ranged
      from 4 to 16 years. During the long-term follow-up, hepatic masses were detected
      via radiological surveillance in Case 3 (in the form of large regenerative
      nodules) and Case 4 (nodular regenerative hyperplasia and cirrhosis).
      CONCLUSIONS: In our study, portal venous thrombosis was detected in the patient
      who died during the acute period only. A study including large numbers of Budd
      Chiari-syndrome patients with Behcet's disease and portal venous thrombosis would
      be helpful to determine the prognostic significance of portal venous thrombosis
      in Budd-Chiari-syndrome patients with Behcet's disease. In addition, patients
      should be monitored regularly for the development of hepatic masses via a long
      term surveillance program.

PMID- 27882060
TI  - Simple and Reliable Method to Quantify the Hepatitis B Viral Load and Replicative
      Capacity in Liver Tissue and Blood Leukocytes.
AB  - BACKGROUND: A functional cure of chronic hepatitis B (CHB) is feasible, but a
      clear view of the intrahepatic viral dynamics in each patient is needed.
      Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the
      viral genome in infected cells, and represents the ideal marker of parenchymal
      colonization. Its relationships with easily accessible peripheral parameters need
      to be elucidated in order to avoid invasive procedures in patients. OBJECTIVES:
      The goal of this study was to design, set up, and validate a reliable and
      straightforward method for the quantification of the cccDNA and total DNA of the
      hepatitis B virus (HBV) in a variety of clinical samples. PATIENTS AND METHODS:
      Clinical samples from a cohort of CHB patients, including liver biopsies in some,
      were collected for the analysis of intracellular HBV molecular markers using
      novel molecular assays. RESULTS: A plasmid construct, including sequences from
      the HBV genome and from the human gene hTERT, was generated as an isomolar multi
      standard for HBV quantitation and normalization to the cellular contents. The
      specificity of the real-time assay for the cccDNA was assessed using Dane
      particles isolated on a density gradient. A comparison of liver tissue from 6
      untreated and 6 treated patients showed that the treatment deeply reduced the
      replicative capacity (total DNA/cccDNA), but had limited impact on the
      parenchymal colonization. The peripheral blood mononuclear cells (PBMCs) and
      granulocytes from the treated and untreated patients were also analyzed.
      CONCLUSIONS: A straightforward method for the quantification of intracellular HBV
      molecular parameters in clinical samples was developed and validated. The
      widespread use of such versatile assays could better define the prognosis of CHB,
      and allow a more rational approach to time-limited tailored treatment strategies.

PMID- 27882058
TI  - Cyclooxygenase-2: A Role in Cancer Stem Cell Survival and Repopulation of Cancer
      Cells during Therapy.
AB  - Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that catalyses the
      synthesis of prostanoids, including prostaglandin E2 (PGE2), a major mediator of
      inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is
      associated with progressive tumour growth, as well as resistance of cancer cells
      to conventional chemotherapy and radiotherapy. These therapies are often
      delivered in multiple doses, which are spaced out to allow the recovery of normal
      tissues between treatments. However, surviving cancer cells also proliferate
      during treatment intervals, leading to repopulation of the tumour and limiting
      the effectiveness of the treatment. Tumour cell repopulation is a major cause of
      treatment failure. The central dogma is that conventional chemotherapy and
      radiotherapy selects resistant cancer cells that are able to reinitiate tumour
      growth. However, there is compelling evidence of an active proliferative
      response, driven by increased COX-2 expression and downstream PGE2 release, which
      contribute to the repopulation of tumours and poor patient outcome. In this
      review, we will examine the evidence for a role of COX-2 in cancer stem cell
      biology and as a mediator of tumour repopulation that can be molecularly targeted
      to overcome resistance to therapy.

PMID- 27882063
TI  - Design, Construction and Evaluation of 1a/JFH1 HCV Chimera by Replacing the
      Intergenotypic Variable Region.
AB  - BACKGROUND: The E2 glycoprotein is an important encoded hepatitis C virus (HCV)
      protein that contains three different variable regions. OBJECTIVES: The aim of
      the present study was to construct an HCV 1a/JFH1 chimeric virus by replacing the
      intergenotypic variable region (igVR) fragment of the highly variable region of
      the E2 gene of the Japanese Fulminant hepatitis genotype 2a JFH1 virus with a
      similar region of HCV genotype 1a. This chimera was produced as a model virus
      with the ability to be cultured. We analyzed the adapted virus and the variations
      of nucleic acids within it. METHODS: Specific primers were designed for the igVR
      of HCV genotype 1a followed by the overlap-PCR method for the synthesis of the
      desired DNA fragment. The amplified igVR-1a chimera gene and pFL-J6/JFH were
      digested by KpnI and BsiWI restriction enzymes, and the fragment was ligated into
      pFL-J6/JFH. The recombinant vector was transformed into Escherichia coli JM109
      strain competent cells. All clones were confirmed by colony PCR using specific
      primers, and the confirmed recombinant vector was sequenced. The recombinant
      vector was targeted for RNA synthesis by T7 RNA polymerase enzyme. RNA
      transfection was performed in the Huh7.5 cell line. Virus production in several
      passages and the evaluated viral load were studied using quantitative real-time
      PCR and ELISA methods. After 30 passages, the RNA virus was extracted and cloned
      in PCDNA3.1 vector, and was then sequenced. RESULTS: Quantitative real-time PCR
      results showed 11,292,514 copies/mL of chimeric virus production in cell culture.
      The virus production was confirmed using ELISA, which showed a virus core
      production of 808.2 pg/mL. The results of cloning and sequencing showed that some
      of the nucleic acids in the chimera virus were changed, affecting the viral
      behavior in the cell culture. CONCLUSIONS: Real-time PCR and ELISA showed high
      levels of production of 1a/JFH1 chimeric HCV in the Huh7.5 cell culture. The
      constructed virus can be used for future studies, including the development of
      new HCV drugs and vaccines.

PMID- 27882062
TI  - Genotyping and Mutation Pattern in the Overlapping MHR Region of HBV Isolates in
      Southern Khorasan, Eastern Iran.
AB  - BACKGROUND: Hepatitis B virus, with 8 known distinct genotypes, is one of the
      most serious health problems which results to liver injuries. The surface gene of
      Hepatitis B virus completely overlaps with the polymerase gene. Mutations in the
      RT gene result in changes in the overlapping hepatitis B surface antigen.
      OBJECTIVES: The present study aimed to evaluate the genotypes and prevalence of
      mutations in a segment of S and RT gene in HBV isolates in Southern Khorasan,
      Iran. METHODS: This was a population-based study comprising 5,235 randomized
      samples for HBV screening. A nested-polymerase chain reaction (PCR) test was
      followed by direct sequencing, and the sequences blast with present sequences of
      NCBI database for genotyping. Alignment and phylogenic analysis was performed
      using MEGA-6 software, and mutation pattern of this segment was finally surveyed
      in Bioedit software. RESULTS: The mean age was 39.07 +/- 14.04 years, with 52.2%
      female and 47.8% male. All isolates belonged to HBV genotype D, sub-genotype D1.
      The most amino acid substitutions of surface protein were Q129H (34.42%) and
      A168V (8.2%), other escape mutants observed in this study were P127L/T, S117G,
      T125M, S143L, D144E and E164D. In the RT gene, Q149K was the most frequently
      identified amino acid substitution (9.83%), followed by L122F (8.19%), N118D/T
      (6.55%), L157M (4.91%), and H124Y (3.27%). CONCLUSIONS: This finding represents
      an ongoing dominancy of HBV genotype D in Eastern Iran, corresponding to other
      parts of Iran. There were a lot of variations in the S gene leading to an escape
      mutation, some of which affected the corresponding area of the RT region.

PMID- 27882064
TI  - The Evaluation and Comparison of Transcriptionally Targeted Noxa and Puma Killer
      Genes to Initiate Apoptosis Under Cancer-Specific Promoter CXCR1 in
      Hepatocarcinoma Gene Therapy.
AB  - BACKGROUND: Cancerous cells proliferate as fast as possible without a proper
      surveillance system. This rapid cell division leads to enormous mutation rates,
      which help a tumor establish. OBJECTIVES: This study evaluated the potential of
      inducing apoptosis using Noxa and Puma in a hepatocarcinoma cell line. METHODS:
      The current study generated two recombinant lentiviruses, pLEX-GCN and pLEX-GCP,
      bearing Noxa and Puma, respectively. Transduction of both genes to
      hepatocarcinoma (HepG2) was verified using fluorescent microscopic analysis,
      western blotting, and quantitative real-time polymerase chain reaction (PCR). To
      evaluate the potential of Noxa and Puma to initiate apoptosis, a caspase-9 real
      time, MTT assay, and a 4', 6-diamidino-2-phenylindole (DAPI) reagent were
      performed to stain apoptotic cells. RESULTS: The data verified successful
      transduction to HepG2 and HEK293T. Higher relative expression of Noxa and Puma
      rather than the untransduced cell line showed these genes are expressed more in
      HepG2 in comparison to HEK293T. The results of the real-time PCR, MTT assay, and
      DAPI reagent illustrated that higher cells initiated apoptosis following Puma
      transduction rather than Noxa. CONCLUSIONS: In this approach, the suicide gene
      was transferred to transformed cells and ignited apoptosis to exterminate them.
      Puma is a more potent killer gene and has higher capabilities to start intrinsic
      apoptosis pathway.

PMID- 27882065
TI  - Hepatic Alveolar Hydatid Cyst: A Brief Review of Published Cases from Iran in the
      Last 20 Years.
AB  - CONTEXT: Echinococcus multilocularis is the cause of alveolar hydatid disease,
      which most commonly involves the liver in more than 90% of cases. This disease is
      endemic in northern Iran. However, there are very few published cases from Iran.
      In this article, we will review all of the published cases of hepatic alveolar
      echinococcosis from Iran regarding all aspects, including clinical, paraclinical,
      and treatment protocols. EVIDENCE ACQUISITION: In this brief review, the
      published cases of hepatic Alveolar Echinococcosis (AE) from Iran were retrieved
      for review via a search in PubMed, Scopus, Google Scholar, IranMedex, scientific
      information database (SID), Magiran, and Irandoc (1995 - 2015) using the keywords
      Echinococcus multilocularis and Iran, Alveolar hydatid cyst and Iran, liver and
      Alveolar hydatid cyst and Iran, and Hepatic alveolar hydatid cyst and Iran. The
      following inclusion criteria were employed: 1, articles must be written in
      English or Farsi; 2, articles must have been published between 1995 and 2015; 3)
      cases must have been confirmed by pathological diagnosis. RESULTS: There were 24
      published cases of liver-involved alveolar hydatid cyst from Iran. The disease
      was more common in young- to middle-aged women in northeast Iran. The most common
      presenting signs and symptoms were abdominal pain with hepatomegaly and liver
      mass. Most of the patients were treated by surgery and albendazole. The few
      unresectable liver masses were treated by medical therapy. No liver
      transplantation for this disease was reported from Iran. CONCLUSIONS: Hepatic
      alveolar hydatid cyst should be considered one of the important differential
      diagnoses of liver masses, especially in endemic areas of the world.

PMID- 27882066
TI  - Bioinformatic Analysis of Codon Usage and Phylogenetic Relationships in Different
      Genotypes of the Hepatitis C Virus.
AB  - BACKGROUND: The hepatitis C virus (HCV) has six major genotypes. The purpose of
      this study was to phylogenetically investigate the differences between the
      genotypes of HCV, and to determine the types of amino acid codon usage in the
      structure of the virus in order to discover new methods for treatment regimes.
      METHODS: The codon usage of the six genotypes of the HCV nucleotide sequence was
      investigated through the online application available on the website Gene
      Infinity. Also, phylogenetic analysis and the evolutionary relationship of HCV
      genotypes were analyzed with MEGA 7 software. RESULTS: The six genotypes of HCV
      were divided into two groups based on their codon usage properties. In the first
      group, genotypes 1 and 5 (74.02%), and in the second group, genotypes 2 and 6
      (72.43%) were shown to have the most similarity in terms of codon usage. Unlike
      the results with respect to determining the similarity of codon usage, the
      phylogenetic analysis showed the closest resemblance and correlation between
      genotypes 1 and 4. The results also showed that HCV has a GC (guanine-cytosine)
      abundant genome structure and prefers codons with GC for translation.
      CONCLUSIONS: Genotypes 1 and 4 demonstrated remarkable similarity in terms of
      genome sequences and proteins, but surprisingly, in terms of the preferred codons
      for gene expression, they showed the greatest difference. More studies are
      therefore needed to confirm the results and select the best approach for
      treatment of these genotypes based on their codon usage properties.

PMID- 27882068
TI  - Transplantation of Deceased Donor Livers With Elevated Levels of Serum
      Transaminases at Shiraz Transplant Center.
AB  - BACKGROUND: The current organ shortage has prompted the use of marginal organs.
      We conducted this retrospective study to present our experience with
      transplanting deceased donor livers with elevated levels of serum transaminases
      and to explain whether elevated levels of serum transaminases in donors affect
      allograft function and survival of the recipients. METHODS: Data of deceased
      donor livers and patients, who underwent liver transplantation from March 2013 to
      March 2015 at Shiraz center for organ transplantation, was reviewed. Liver donors
      with aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) level
      of more than 500 IU/l and their related recipients were considered as the case
      group (n = 24) and the others were considered as the control group (n = 834).
      RESULTS: In the case group, the medians of levels of serum AST and ALT of donors
      were 834 +/- 425 IU/L (range: 250 - 2285) and 507 +/- 367 IU/L (range: 100 -
      1600), respectively. Recipients were followed for a median of 13.6 +/- 9 months
      (range: 7 - 28.4). Post-transplant complications were acute rejection (n = 5),
      infection (n = 3), portal vein thrombosis (n = 3), bile duct stricture (n = 1),
      and hepatic artery stenosis (n = 1). The one-year survival rate of the patients
      was 91.7%. Demographics, post-transplant complications and one-year survival
      rates were not significantly different between the two study groups. CONCLUSIONS:
      Transplanting deceased donor livers with markedly elevated liver enzymes may be
      an acceptable choice for expanding the donor pool.

PMID- 27882067
TI  - Bioinformatic Identification of Rare Codon Clusters (RCCs) in HBV Genome and
      Evaluation of RCCs in Proteins Structure of Hepatitis B Virus.
AB  - BACKGROUND: Hepatitis B virus (HBV) as an infectious disease that has nine
      genotypes (A - I) and a 'putative' genotype J. OBJECTIVES: The aim of this study
      was to identify the rare codon clusters (RCC) in the HBV genome and to evaluate
      these RCCs in the HBV proteins structure. METHODS: For detection of protein
      family accession numbers (Pfam) in HBV proteins, the UniProt database and Pfam
      search tool were used. Protein family accession numbers is a comprehensive and
      accurate collection of protein domains and families. It contains annotation of
      each family in the form of textual descriptions, links to other resources and
      literature references. Genome projects have used Pfam extensively for large-scale
      functional annotation of genomic data; Pfam database is a large collection of
      protein families, each represented by multiple sequence alignments and hidden
      Markov models (HMMs). The Pfam search tools are databases that identify Pfam of
      proteins. These Pfam IDs were analyzed in Sherlocc program and the location of
      RCCs in HBV genome and proteins were detected and reported as translated EMBL
      nucleotide sequence data library (TrEMBL) entries. The TrEMBL is a computer
      annotated supplement of SWISS-PROT that contains all the translations of European
      molecular biology laboratory (EMBL) nucleotide sequence entries not yet
      integrated in SWISS-PROT. Furthermore, the structures of TrEMBL entries proteins
      were studied in the PDB database and 3D structures of the HBV proteins and
      locations of RCCs were visualized and studied using Swiss PDB Viewer software(r).
      RESULTS: The Pfam search tool found nine protein families in three frames.
      Results of Pfams studies in the Sherlocc program showed that this program has not
      identified RCCs in the external core antigen (PF08290) and truncated HBeAg gene
      (PF08290) of HBV. By contrast, the RCCs were identified in gene of hepatitis core
      antigen (PF00906 and the residues 224 - 234 and 251 - 255), large envelope
      protein S (PF00695 and the residues 53-56 and 70 - 84), X protein (PF00739 and
      the residues 10 - 24, 29 - 83, 95 - 99. 122 - 129, 139 - 143), DNA polymerase
      (viral) N-terminal domain (PF00242 and the residues 59 - 62, 214 - 217, 407 -
      413) and protein P (Pf00336 and the residues 225 - 228). In HBV genome, seven
      RCCs were identified in the gene area of hepatitis core antigen, large envelope
      protein S and DNA polymerase, while protein structures of TrEMBL entries
      sequences found in Sherlocc program outputs were not complete. CONCLUSIONS: Based
      on the location of detected RCCs in the structure of HBV proteins, it was found
      that these RCCs may have a critical role in correct folding of HBV proteins and
      can be considered as drug targets. The results of this study provide new and deep
      perspectives about structure of HBV proteins for further researches and designing
      new drugs for treatment of HBV.

PMID- 27882069
TI  - Hepatitis C and G Virus Infection Prevalence Among Hemodialysis Patients and
      Associated Risk Factors in the Hormozgan Province of Southern Iran.
AB  - BACKGROUND: Infection with blood-borne viruses including hepatitis C (HCV) and
      hepatitis G (HGV) viruses is a substantial health problem. Varying prevalences of
      these infections in different studies reflect the role of predisposing risk
      factors in different countries or even different regions of a country.
      OBJECTIVES: The objective of the present survey was to assess the prevalences of
      HCV and HGV virus infections among hemodialysis (HD) patients in Bandar Abbas,
      Hormozgan, Iran, 2015. METHODS: A total of 149 subjects with chronic renal
      failure undergoing HD at Shahid Mohammadi hospital in the Hormozgan province of
      southern Iran from January 1, 2015 to March 31, 2015 were evaluated for anti-HCV
      and antibodies against HGV E2 glycoprotein by census sampling method. Thereafter,
      all of the specimens were evaluated for molecular assays using polymerase chain
      reaction (PCR) and other techniques. Investigated data were recorded for each
      participant in a pre-designed data collection sheet. All statistical analyses
      were conducted using the Statistical Package for the Social Sciences (SPSS)
      version 19 for Windows by t-test and chi-square test (chi2). RESULTS: The mean
      age of patients was 56.23 +/- 12.35 years (minimum age 18, maximum age 85). Both
      kinds of assays determined that five (3.36%) patients were HCV positive, whereas
      no HGV positives were diagnosed. The prevalence of HCV is associated with longer
      duration of HD (P value = 0.008), history of blood transfusion (P value = 0.037)
      and drug addiction (P value = 0.035). CONCLUSIONS: History of drug addiction
      and/or blood transfusion and longer duration of HD treatment were the main risk
      factors determining the prevalence of HCV infection in the Hormozgan province of
      southern Iran in 2015. However, the values observed in the present investigation
      reflect the effective management techniques imposed by healthcare authorities and
      relevant organizations in recent years.

PMID- 27882070
TI  - Serological Patterns and Molecular Characterization of Occult Hepatitis B Virus
      Infection among Blood Donors.
AB  - BACKGROUND: Hepatitis B infections, characterized by the presence of a viral
      genome without detectable hepatitis B surface antigen (HBsAg; Occult hepatitis B
      infection [OBI]), have been reported recently. OBJECTIVES: We performed
      serological and molecular characterization of OBI among blood donors at Jiangsu
      province blood center during years 2013 and 2014. METHODS: All donor samples were
      routinely screened by double enzyme-linked immunosorbent assay (ELISA) for
      hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus
      (HIV), Treponema pallidum (TP), and alanine aminotransferase (ALT). Single
      reactive, nonreactive, and ALT-elevated samples were pooled or resolved by
      nucleic acid testing (NAT). Seromarkers were examined in HBsAg-/DNA+ samples.
      After 1 to 12 months of follow up, seromarkers were screened again to verify OBI
      samples. RESULTS: We studied 157119 samples from blood donors. A total of 154397
      ELISA nonreactive donor samples were identified, and HBV DNA was detected in 81
      samples; no samples were positive for HIV or HCV RNA. Hepatitis B virus viral
      loads in most donors were less than 20 - 200 IU/mL. There was only one HBsAg
      positive sample. Eighty HBsAg-/DNA+ samples were evaluated further. Of these
      samples, 85% (68/80) were reactive for anti-HBc and 36.2% (29/800) were reactive
      for anti-HBc and anti-HBs; 11.3% (9/80) did not have any detectable serological
      markers. Twenty-nine donors were followed up. One was HBsAg ELISA positive, and
      of six seronegative donors, all had anti-HBc and anti-HBs, but were negative for
      DNA. Samples were HBV genotypes B, C and D. Mutations in the S region of HBV DNA
      included S114T, G119R, P120S, T125M, C139Y, T140I, C147W, T148A, A159V/G, E164D,
      V168A, and R169C. CONCLUSIONS: Overall, we found that OBI was rare, but that the
      prevalence of OBI was slightly higher in Jiangsu than in other areas of China.

PMID- 27882071
TI  - Pigmentation Effect of Rice Bran Extracted Minerals Comprising Soluble Silicic
      Acids.
AB  - Our investigation focused on identifying melanogenesis effect of soluble minerals
      in rice bran ash extract (RBE) which include orthosilicic acid (OSA). Melanocytes
      were apparently normal in terms of morphology. It was, however, shown that they
      were stressed a little in the RBE and OSA added media in aspect of LDH activity.
      Melanin synthesis and intracellular tyrosinase activity were increased by
      treatment of RBE which is similar to that of OSA. The Western blotting results
      showed that TRP-1, tyrosinase, and MITF expression levels were 2-3 times higher
      in the OSA and RBE groups compared to the control group which promoted melanin
      synthesis through CREB phosphorylation. Moreover, histology and
      immunohistochemistry were shown to have similar result to that of protein
      expression. As a result, minerals which comprise orthosilicic acid has the
      potential to promote melanogenesis and both RBE and OSA have similar cell
      viability, protein expression, and immunostaining results, suggesting that RBE
      comprises specific minerals which promote melanin synthesis through increasing of
      MITF and CREB phosphorylation. Therefore, RBE could be used as a novel
      therapeutic approach to combat melanin deficiency related diseases by stimulating
      melanocytes via its soluble Si and mineral components.

PMID- 27882072
TI  - Radix Astragali Stimulates p38 MARK Phosphorylation in Pediatric Patients with
      beta-Thalassemia.
AB  - A previous study conducted by our group demonstrated that Radix Astragali
      compounded with Codonopsis pilosula and Plastrum testudinis was effective in
      treating pediatric beta-thalassemia in a randomized, controlled clinical trial.
      However, the mechanism of action that underpins this treatment remains to be
      elucidated. Blood was collected from patients participating in this clinical
      trial and nucleated red blood cell-enriched mononuclear cells were isolated to
      facilitate the extraction of RNA and protein. RT-PCR was used to monitor the
      expression of globin genes and p38 MAPK, and total and phosphorylated p38 MAPK
      expression was assessed using Western blot analysis. Expression of alpha-, beta-,
      and Agamma-globin mRNAs was not significantly affected following treatment with
      R. Astragali or the compounded formulation. However, Ggamma-globin mRNA levels
      increased significantly in both treatment groups (when compared with pretreatment
      levels) following 12 weeks of treatment. Moreover, posttreatment Ggamma-globin
      expression was significantly higher in both treatment groups compared with the
      control group. Although neither p38 MAPK mRNA nor protein levels were affected by
      the treatments, posttreatment phosphorylation of p38 MAPK was significantly
      increased in the R. Astragali and compounded formulation groups compared with the
      control group. These data suggest that the molecular mechanisms that underpin the
      efficacious use of R. Astragali (and its compounded formulation) in pediatric
      beta-thalassemia treatment facilitate the induction of Ggamma-globin expression
      following activation of p38 MAPK.

PMID- 27882073
TI  - Standard versus Abdominal Lifting and Compression CPR.
AB  - Background. This study compared outcomes of abdominal lifting and compression
      cardiopulmonary resuscitation (ALP-CPR) with standard CPR (STD-CPR). Materials
      and Methods. Patients with cardiac arrest seen from April to December 2014 were
      randomized to receive standard CPR or ALP-CPR performed with a novel abdominal
      lifting/compression device. The primary outcome was return of spontaneous
      circulation (ROSC). Results. Patients were randomized to receive ALP-CPR (n = 40)
      and STD-CPR (n = 43), and the groups had similar baseline characteristics. After
      CPR, 9 (22.5%) and 7 (16.3%) patients in the ALP-CPR and STD-CPR groups,
      respectively, obtained ROSC. At 60 minutes after ROSC, 7 (77.8%) and 2 (28.6%)
      patients, respectively, in the ALP-CPR and STD-CPR groups survived (P = 0.049).
      Patients in the ALP-CPR group had a significantly higher heart rate and lower
      mean arterial pressure (MAP) than those in the STD-CPR group (heart rate: 106.8
      versus 79.0, P < 0.001; MAP: 60.0 versus 67.3 mm Hg, P = 0.003). The
      posttreatment PCO2 was significantly lower in ALP-CPR group than in STD-CPR group
      (52.33 versus 58.81, P = 0.009). PO2 was significantly increased after ALP-CPR
      (45.15 to 60.68, P < 0.001), but it was not changed after STD-CPR. PO2 after CPR
      was significantly higher in the ALP-CPR group (60.68 versus 44.47, P < 0.001).
      There were no differences between genders and for patients who are > 65 or <= 65
      years of age. Conclusions. The abdominal lifting and compression cardiopulmonary
      resuscitation device used in this study is associated with a higher survival rate
      after ROSC than standard CPR.

PMID- 27882074
TI  - Survival Prediction and Feature Selection in Patients with Breast Cancer Using
      Support Vector Regression.
AB  - The Support Vector Regression (SVR) model has been broadly used for response
      prediction. However, few researchers have used SVR for survival analysis. In this
      study, a new SVR model is proposed and SVR with different kernels and the
      traditional Cox model are trained. The models are compared based on different
      performance measures. We also select the best subset of features using three
      feature selection methods: combination of SVR and statistical tests, univariate
      feature selection based on concordance index, and recursive feature elimination.
      The evaluations are performed using available medical datasets and also a Breast
      Cancer (BC) dataset consisting of 573 patients who visited the Oncology Clinic of
      Hamadan province in Iran. Results show that, for the BC dataset, survival time
      can be predicted more accurately by linear SVR than nonlinear SVR. Based on the
      three feature selection methods, metastasis status, progesterone receptor status,
      and human epidermal growth factor receptor 2 status are the best features
      associated to survival. Also, according to the obtained results, performance of
      linear and nonlinear kernels is comparable. The proposed SVR model performs
      similar to or slightly better than other models. Also, SVR performs similar to or
      better than Cox when all features are included in model.

PMID- 27882075
TI  - In Silico Evaluation of the Potential Antiarrhythmic Effect of Epigallocatechin-3
      Gallate on Cardiac Channelopathies.
AB  - Ion channels are transmembrane proteins that allow the passage of ions according
      to the direction of their electrochemical gradients. Mutations in more than 30
      genes encoding ion channels have been associated with an increasingly wide range
      of inherited cardiac arrhythmias. In this line, ion channels become one of the
      most important molecular targets for several classes of drugs, including
      antiarrhythmics. Nevertheless, antiarrhythmic drugs are usually accompanied by
      some serious side effects. Thus, developing new approaches could offer added
      values to prevent and treat the episodes of arrhythmia. In this sense, green tea
      catechins seem to be a promising alternative because of the significant effect of
      Epigallocatechin-3-Gallate (E3G) on the electrocardiographic wave forms of guinea
      pig hearts. Thus, the aim of this study was to evaluate the benefits-risks
      balance of E3G consumption in the setting of ion channel mutations linked with
      aberrant cardiac excitability phenotypes. Two gain-of-function mutations, Nav1.5
      p.R222Q and Nav1.5-p.I141V, which are linked with cardiac hyperexcitability
      phenotypes were studied. Computer simulations of action potentials (APs) show
      that 30 MUM E3G reduces and suppresses AP abnormalities characteristics of these
      phenotypes. These results suggest that E3G may have a beneficial effect in the
      setting of cardiac sodium channelopathies displaying a hyperexcitability
      phenotype.

PMID- 27882076
TI  - Redox dependent metabolic shift in Clostridium autoethanogenum by extracellular
      electron supply.
AB  - BACKGROUND: Microbial electrosynthesis is a novel approach that aims at shifting
      the cellular metabolism towards electron-dense target products by extracellular
      electron supply. Many organisms including several acetogenic bacteria have been
      shown to be able to consume electrical current. However, suitable hosts for
      relevant industrial processes are yet to be discovered, and major knowledge gaps
      about the underlying fundamental processes still remain. RESULTS: In this paper,
      we present the first report of electron uptake by the Gram-positive, ethanol
      producing acetogen, Clostridium autoethanogenum. Under heterotrophic conditions,
      extracellular electron supply induced a significant metabolic shift away from
      acetate. In electrically enhanced fermentations on fructose, acetate production
      was cut by more than half, while production of lactate and 2,3-butanediol
      increased by 35-fold and threefold, respectively. The use of mediators with
      different redox potential revealed a direct dependency of the metabolic effect on
      the redox potential at which electrons are supplied. Only electrons delivered at
      a redox potential low enough to reduce ferredoxin caused the reported effect.
      CONCLUSIONS: Production in acetogenic organisms is usually challenged by cellular
      energy limitations if the target product does not lead to a net energy gain as in
      the case of acetate. The presented results demonstrate a significant shift of
      carbon fluxes away from acetate towards the products, lactate and 2,3-butanediol,
      induced by small electricity input (~0.09 mol of electrons per mol of substrate).
      This presents a simple and attractive method to optimize acetogenic fermentations
      for production of chemicals and fuels using electrochemical techniques. The
      relationship between metabolic shift and redox potential of electron feed gives
      an indication of possible electron-transfer mechanisms and helps to prioritize
      further research efforts.

PMID- 27882078
TI  - Debridement in chronic osteomyelitis with benign osteopetrosis: A case report.
AB  - Osteopetrosis is a rare bone disease caused by metabolic imbalances as a result
      of genetic mutations. For instance, autosomal dominant osteopetrosis is caused by
      a missense mutation of the C1CN7 gene. This was first reported in 1904 and is
      thought to be caused by osteoclastic dysfunction and an impaired bone resorption
      ability. An accumulation of cortical bone mass during the remodeling of the
      medullary bone may increase the bone density and give rise to a hard marble
      consistency. Osteopetrosis can be divided into benign and malignant forms;
      however, no curative treatment exists for benign osteopetrosis. The management of
      complications, such as chronic osteomyelitis and fractures, serves a key role in
      influencing the patient survival rates. Previous studies have demonstrated that a
      combined treatment of hyperbaric oxygen (HBO) lavage for debridement of the
      necrotic region and high-dose systemic antibiotics may be effective in the
      management of osteopetrosis. The present study reported a case of chronic
      mandible osteomyelitis and fistula occurring in association with maxillary
      sinusitis, who was successfully treated by through nasal endoscopy, using
      repeated flushing and cleaning every 2 weeks as a form of debridement, in the
      absence of high-dose antibiotics and HBO.

PMID- 27882079
TI  - Overexpression of caveolin-1 reduces Taxol resistance in human osteosarcoma cells
      by attenuating PI3K-Akt-JNK dependent autophagy.
AB  - Caveolin-1 (CAV-1), which is an oncoprotein and a tumor suppressor, is highly
      expressed in normal osteoblasts. Although researchers have investigated its role
      in human osteosarcoma, the mechanism of caveolin-1 action in osteosarcoma remains
      unknown. In the present study, Saos-2 and U-2 OS cells were cultured with a
      continuous induction protocol of gradually increasing Taxol concentration for 6
      months to establish drug-resistant cell lines. CAV-1 expression levels in
      osteosarcoma cells were detected via western blotting and quantitative polymerase
      chain reaction. CAV-1 knockdown was achieved using a short hair-pin RNA
      lentivirus vector, and cell viability was analyzed by MTT assay. The effect of
      caveolin-1 on autophagy was investigated, and the downregulation of caveolin-1
      and increased autophagy was identified in Taxol-resistant osteosarcoma cells. In
      addition, the results of the present study demonstrated that downregulation of
      caveolin-1 promotes autophagy and induces osteosarcoma cell resistance to Taxol.
      Notably, overexpression of CAV-1 resensitized drug-resistant cells to Taxol via
      declined autophagy. In conclusion, CAV-1 was demonstrated to be downregulated in
      Taxol-resistant osteosarcoma cells, and overexpression of CAV-1 in human
      osteosarcoma cells suppressed Taxol resistance by attenuating PI3K-Akt-JNK
      dependent autophagy. The present findings suggest that further investigation into
      CAV-1's role in Taxol resistance is warranted. In the future, detection of CAV-1
      may be used as an indicator to evaluate the treatment and prognosis of patients
      with osteosarcoma.

PMID- 27882077
TI  - Potential protective effects of autophagy activated in MPP+ treated astrocytes.
AB  - Astrocytes, which have various important functions, have previously been
      associated with Parkinsons disease (PD), particularly in 1-methyl-4
      phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the
      enzymatic activity of monoamine oxidase B, which is predominantly located in
      astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an
      evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs
      in response to various types of stress, including starvation and oxidative
      stress. Lithium treatment has previously been shown to induce autophagy in
      astrocytes by inhibiting the enzyme inositol monophosphatase, which may aid in
      the treatment of neurodegenerative diseases, including Huntington's disease, in
      which the toxic protein is an autophagy substrate. Therefore, using western
      blotting and MTT assay, the present study aimed to investigate the protective
      effects of lithium-induced autophagy against astrocyte injury caused by MPP+
      treatment, as well as the potential underlying mechanisms. The results of the
      present study suggested that lithium was able to induce autophagy in astrocytes
      treated with MPP+, and this likely occurred via activation of the
      phosphoinositide 3-kinase/AKT pathway.

PMID- 27882080
TI  - A novel KRT5 mutation associated with generalized severe epidermolysis bullosa
      simplex in a 2-year-old Chinese boy.
AB  - Mutations in keratin 5 (KRT5) or KRT14 genes are responsible for the most severe
      form of epidermolysis bullosa simplex (EBS), which is EBS generalized severe (EBS
      gen sev). To date, only four pathogenic mutations (p.Arg165Ser and p.Lys199Asn in
      KRT5; p.Arg125Cys and p.Arg125His in KRT14) have been reported to be responsible
      for EBS-gen sev in the Chinese population. In the present study, a 2-year-old
      Chinese boy was clinically suspected to suffer from EBS, and thus Sanger
      sequencing was performed in the extracted genomic DNA samples from the patient,
      his parents and 100 healthy controls. A novel de novo heterozygous missense
      mutation c.503A>G (p.Glu168Gly) located at the N-terminal end segment of the 1A
      domain in KRT5 was identified by molecular analysis. In silico analysis tools
      were used to predict the pathogenicity of the novel missense mutation. A
      diagnosis of EBS-gen sev was thus confirmed according to the clinical
      presentations and molecular results.

PMID- 27882081
TI  - Effects of different sutures on fibrosis and wound healing in a rabbit model of
      corneal wounds.
AB  - The aim of the study was to investigate wound healing and scar formation in
      rabbit corneal lamellar wounds repaired with simple interrupted sutures (SIS) or
      horizontal mattress sutures (HMS). Two parallel 'I'-shaped lamellar cornea wounds
      were created in one eye of 40 white New Zealand rabbits, while 5 uninjured
      rabbits were sacrificed to serve as normal controls. One side of the wounds, in
      the test rabbits, was closed with SIS, while the other side was treated with HMS.
      Ten days later, the stitches were removed under anesthesia. The animals were
      sacrificed on days 14 and 21, and months 3 and 6 after the suturing surgery, and
      corneal samples were subjected to histological and immunofluorescent studies:
      alpha-smooth muscle actin (alpha-SMA) and vimentin were used to detect
      myofibroblasts and fibroblasts, respectively, and collagen type I and III was
      used to detect extracellular matrix (ECM) deposition. Relevant mRNA levels were
      assessed by quantitative polymerase chain reaction (qPCR) to elucidate the
      differences in wound healing and formation of fibrosis. Macroscopic and
      hematoxylin and eosin staining observations showed that the two sides of the
      wounds developed the most prominent fibrotic tissue on day 21. The
      immunofluorescence and qPCR results showed that HMS wounds produced increased
      alpha-SMA, vimentin and collagen type III compared to the SIS wounds on day 14 or
      21. The collagen type I expression showed no distinctive difference in SIS and
      HMS wounds. In conclusion, corneal lamellar wounds treated with SIS developed
      less fibrotic-related proteins and related mRNA in the early stages of wound
      healing than wounds treated with HMS. Although differences were not distinct
      after 3 months, the results of the present study suggest a benefit in choosing
      SIS over HMS, as at least the initial fibrotic process seems more benign with
      SIS. Corneal wounds should be carefully sutured, ensuring the tissue is well
      aligned.

PMID- 27882082
TI  - Early identification of hypoxic-ischemic encephalopathy by combination of
      magnetic resonance (MR) imaging and proton MR spectroscopy.
AB  - Brain damage following a perinatal hypoxic-ischemic encephalopathy (HIE) can be
      diagnosed by different techniques. The aim of the present study was to combine
      magnetic resonance (MR) imaging with proton MR spectroscopy in HIE diagnosis and
      to evaluate their correlation with outcome. A prospective observational cohort
      study was performed between February 2012 and February 2013. Consecutive
      newborns, 24 full-term neonates with HIE (mild to moderate and severe group) and
      5 normal neonates, were included. Two sequential MR studies were performed; a
      conventional MR imaging for observation in T1 weighted image (WI) and T2WI, and
      proton MR spectroscopy for observation in the left or right basal ganglia and
      thalamus. MR images were assessed and scored by two neuroradiologists who were
      blinded to the clinical condition of the infants. The mild to moderate group
      (n=13) and severe group (n=11) were similar in the visualization of punctate
      hyperintensity lesions on T1WI and brain edema on T2WI. The differences of N
      acetylaspartate/creatine (Cr), choline/Cr and lactate/Cr in the basal ganglia and
      thalamus in the HIE group were significantly different (P<0.05) compared with the
      control group, while no significant difference was identified between the mild to
      moderate and severe group (P>0.05). In conclusion, MR spectroscopy is a
      complementary tool for the diagnosis of HIE.

PMID- 27882084
TI  - Staged bilateral single-port thoracoscopic lung volume reduction surgery: A
      report of 11 cases.
AB  - The aim of the present study was to investigate the feasibility and efficacy of
      staged bilateral single-port thoracoscopic lung volume reduction surgery (LVRS)
      for patients with chronic obstructive pulmonary emphysema (COPE). Eleven male
      patients with a mean age of 60.27+/-12.11 years with bilateral COPE and bullae
      were admitted to the Department of Thoracic Surgery, Xuzhou Central Hospital from
      January 2013 to June 2014. The patients underwent staged bilateral single-port
      thoracoscopic LVRS. The hyperinflated bullae were resected using endoscopic
      staplers (Endo-GIA), followed by continuous suture and biological glue for
      reinforcement of the margin. In addition, pulmonary function, blood gas assay, 6
      min walk distance (6MWD) and life quality evaluated by a short form 36-item
      health survey questionnaire (SF-36) were recorded before and after LVRS,
      respectively. All the patients survived after surgery. The chest tube drainage
      time was 9.09+/-1.31 days and postoperative hospital stay was 15.73+/-2.75 days,
      with 5 cases of persistent air leakage and 7 cases of pulmonary infection which
      were finally cured. The patients were followed up for 3 to 12 months, and the
      pulmonary function, partial pressure of oxygen (pO2), 6MWD and life quality after
      unilateral or bilateral LVRS were improved compared to these parameters before
      surgery. However, there was no significant difference between unilateral and
      bilateral LVRS in terms of life quality. In conclusion, staged bilateral single
      port thoracoscopic LVRS may improve the short-term life quality of patients with
      COPE.

PMID- 27882083
TI  - Dimethyloxaloylglycine increases bone repair capacity of adipose-derived stem
      cells in the treatment of osteonecrosis of the femoral head.
AB  - Mesenchymal stem cells have been widely studied to promote local bone
      regeneration of osteonecrosis of the femoral head (ONFH). Previous studies
      observed that dimethyloxaloylglycine (DMOG) enhanced the angiogenic and
      osteogenic activity of mesenchymal stem cells by activating the expression of
      hypoxia inducible factor-1alpha (HIF-1alpha), thereby improving the bone repair
      capacity of mesenchymal stem cells. In the present study, it was investigated
      whether DMOG could increase the bone repair capacity of adipose-derived stem
      cells (ASCs) in the treatment of ONFH. Western blot analysis was performed to
      detect HIF-1alpha protein expression in ASCs treated with different
      concentrations of DMOG. The results showed DMOG enhanced HIF-1alpha expression in
      ASCs in a dose-dependent manner at least for 7 days. Furthermore, DMOG-treated
      ASCs were transplanted into the necrotic area of a rabbit model of ONFH to treat
      the disease. Four weeks later, micro-computed tomography (CT) quantitative
      analysis showed that 58.8+/-7.4% of the necrotic area was regenerated in the DMOG
      treated ASCs transplantation group, 45.5+/-3.4% in normal ASCs transplantation
      group, 25.2+/-2.8% in only core decompression group and 10.6+/-2.6% in the
      untreated group. Histological analysis showed that transplantation of DMOG
      treated ASCs clearly improved the bone regeneration of the necrotic area compared
      with the other three groups. Micro-CT and immunohistochemical analysis
      demonstrated the revasculation of the necrotic area were also increased
      significantly in the DMOG-treated ASC group compared with the control groups.
      Thus, it is hypothesized that DMOG could increase the bone repair capacity of
      ASCs through enhancing HIF-1alpha expression in the treatment of ONFH.

PMID- 27882085
TI  - Knockdown of KLK11 inhibits cell proliferation and increases oxaliplatin
      sensitivity in human colorectal cancer.
AB  - It has been reported that kallikrein 11 (KLK11) is crucially involved in the
      development and progression of various types of cancer. However, the molecular
      mechanisms that underlie the involvement of KLK11 in aberrant colorectal cancer
      (CRC) cell growth remain largely unclear. The aim of the present study was to
      investigate the role of KLK11 and the effects of KLK11 on oxaliplatin (L-OHP)
      chemosensitivity by knocking down KLK11 in LOVO and HCT-8 cells. Loss-of-function
      assays revealed KLK11 inhibition significantly inhibited growth and induced
      apoptosis of CRC cells in vitro. Notably, further experiments found that
      knockdown of KLK11 expression increased the L-OHP chemosensitivity of CRC cells.
      KLK11 inhibition of increased L-OHP-induced apoptosis may be associated with
      activation of caspase-3 cleavage and the apoptosis signaling pathway. The present
      results indicated that KLK11 may be an potential target of interest for future
      research into therapies for CRC.

PMID- 27882086
TI  - Effects of the short-term application of pantoprazole combined with aspirin and
      clopidogrel in the treatment of acute STEMI.
AB  - The aim of the present study was to determine the effects of the short-term
      application of pantoprazole on the co-treatment of acute ST-segment elevation
      myocardial infarction (STEMI) with aspirin and clopidogrel. A total of 207 acute
      patients showing primary symptoms of STEMI, who received successful emergent
      percutaneous coronary intervention treatment during hospitalization were randomly
      divided into two groups. In the test group proton pump inhibitors (PPIs), the
      patients were treated with a combination of aspirin and clopidogrel and
      pantoprazole, while those in the control group were treated only with aspirin and
      clopidogrel. Gastrointestinal bleeding events and major adverse cardiac events
      (MACEs) were observed in the two groups. Gastrointestinal bleeding events of the
      two groups mostly occurred within the first week of hospitalization, although the
      incidence in the PPIs group was significantly higher than that in the control
      group (p<0.05). However, no significant difference was observed for the incidence
      of MACEs between the two groups (p>0.05). In conclusion, the results of the
      present study have shown that the short-term application of pantoprazole combined
      with aspirin and clopidogrel does not increase the incidence of MACEs in patients
      with acute STEMI, reduces the risk of gastrointestinal bleeding, and is thus
      worth promoting clinically, particularly for high-risk groups.

PMID- 27882087
TI  - Increased apoptosis rate of human decidual cells and cytotrophoblasts in patients
      with recurrent spontaneous abortion as a result of abnormal expression of CDKN1A
      and Bax.
AB  - In the present study, we analyzed the proliferation and apoptosis of trophoblasts
      and human decidual cells in patients with recurrent spontaneous abortion and the
      related cellular pathway mechanism. Thirty-four patients with recurrent abortion
      and 30 healthy pregnant women undergoing planned artificial abortion were
      selected. The trophoblast and decidual cells were collected by negative pressure
      aspiration technique. TUNEL method was used to detect the apoptosis rate.
      Immunohistochemical method was used for detection of TP53 protein. Quantitative
      real-time PCR was used for detection of the relative expression level of CDKN1A
      and Bax mRNA. It was found that the cell apoptosis rate in the recurrent
      miscarriage group was significantly increased and the expression levels of TP53
      protein, CDKN1A and Bax mRNA were also significantly increased (p<0.05). In
      conclusion, the trophoblast and decidual cells of patients with recurrent
      abortion were obviously apoptotic, which was probably related to abnormal
      expression of the CDKN1A and Bax genes mediated by TP53 protein through cellular
      pathways.

PMID- 27882088
TI  - Study on the resistance mechanism via outer membrane protein OprD2 and metal beta
      lactamase expression in the cell wall of Pseudomonas aeruginosa.
AB  - The aim of the present study was to evaluate the imipenem-resistant mechanism via
      the outer membrane protein (OMP) OprD2 and metal beta-lactamase expression in the
      cell wall of Pseudomonas aeruginosa. The Pseudomonas aeruginosa was clinically
      separated and validated by VITEK-2 full-automatic bacteria analyzer. Drug
      resistance, sensitive antibiotics and minimum inhibitory concentration (MIC) were
      tested using the drug sensitivity analysis system. The phenotype positive strains
      of MBL genes were screened using the Kirby-Bauer diffusion method by adding metal
      ion-chelating agent EDTA on the imipenem susceptibility paper. IMP-1, VIM-1 and
      SPM metaloenzyme genes were tested by polymerase chain reaction (PCR)-telomeric
      repeat amplification protocol (TRAP). The OMP OprD2 genes were tested by PCR
      TRAP, and the protein expression was tested using western blot analysis. The
      location of OMP OprD2 was confirmed using the sodium salicylate inhibition test.
      The results showed that 80 portions (40%) of MBL-positive strains were screened
      out of 200 specimens. Imipenem-resistant Pseudomonas aeruginosa (IRPA) and MIC
      values were significantly higher than quality control bacteria and control
      bacteria (P<0.05). A total of 35 cases with IMP-1 positive, 20 with VIM-1
      positive, 16 with SPM positive, 5 with 2 positive genes and 4 with 3 positive
      genes were screened among MBL positive strains. A total of 150 portions (75%) of
      OprD2 deficiencies were screened from 200 specimens. The standard strains and
      sensitive strains showed OprD2 protein bands at 45 kDa while no OprD2 protein
      bands appeared in OprD2 deficiency strains. It was in accordance with gene
      detection. In conclusion, OMP OprD2 deficiency and MBL phenotype positivity may
      be important mechanisms of IRPA.

PMID- 27882089
TI  - Gender impact on the correlation between thyroid function and serum lipids in
      patients with differentiated thyroid cancer.
AB  - The present study aimed to explore the association between thyroid stimulating
      hormone (TSH) and serum lipids in patients with differentiated thyroid cancer
      (DTC), with a focus on the risk of hyperlipidemia between different genders. The
      study included 352 DTC patients who were ready to receive I-131 therapy as well
      as 352 matched normal controls. In the DTC group, 157 patients were monitored for
      TSH and lipid parameters prior to and after 1 month of thyroxine therapy. Results
      were analyzed using t-tests, Pearson bivariate correlation and binary logistic
      regression analyses. All participants were divided into 3 subgroups according to
      TSH levels: Subgroup 1 (normal TSH level), subgroup 2 (TSH between 5 and 30
      uIU/ml), and subgroup 3 (TSH >30 uIU/ml). Serum total cholesterol (TC),
      triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels were
      significantly higher in the DTC group than in the control group. The levels of
      these parameters decreased after thyroxine therapy and significant positive
      correlations were observed between TSH and TC, and TG and LDL-C in both genders.
      Binary logistic regression demonstrated that female DTC patients had higher risks
      of developing hyperlipidemia than male patients, and these risks increased when
      TSH increased. For example, the odds ratios (ORs) of high TC in subgroup 2 were
      3.30 in males and 4.60 in females, respectively. However, in subgroup 3, the ORs
      were 9.40 in males and 13.12 in females, respectively. The results of the present
      study showed that after thyroidectomy, the risk of dyslipidemia markedly
      increased in DTC patients. More importantly, female patients had a higher risk
      than male patients.

PMID- 27882090
TI  - Clinical treatment of malignant hyperthermia in three cases.
AB  - Malignant hyperthermia (MH) is a rare life threatening inherited disorder that is
      triggered by drugs used for general anesthesia in susceptible persons. The
      symptoms include rapid increase of body temperature and severe muscle
      contractions. The present study includes 3 cases of MH and highlights the timely
      identification of symptoms for rescuing the patient. In case I, a 7-year-old male
      child underwent surgery with ketamine at a dose of 250 mg. After 4 h of
      operation, the child went through convulsions, high fever and succumbed within a
      few hours. High fever was not detected in a timely manner, which is one of the
      main symptoms of MH. In case II, a 12-year-old male child had convulsions and
      high fever after simple surgery caused by MH. Once confirmed, immediate measures
      were taken to lower the body temperature and the child was rescued. In case III,
      a male 57-year-old was admitted to hospital due to paraplegia. The patient
      underwent more critical conditions once symptoms of MH appeared. Additionally,
      antidote dantrolene was unavailable in the first and third case; thus, the
      progression of disease was not alleviated although active symptomatic and
      supportive treatment were employed.

PMID- 27882091
TI  - Exendin-4 antagonizes Abeta1-42-induced attenuation of spatial learning and
      memory ability.
AB  - beta-amyloid protein (Abeta) accumulation in cerebral centers involved in
      cognition and memory is a pivotal pathological feature of Alzheimer's disease
      (AD). The onset process of type 2 diabetes mellitus (T2DM) has a number of
      similarities compared with AD. Thus, it is hypothesized that the pharmacological
      therapy employed for the treatment of T2DM may help to prevent and ameliorate the
      symptoms of AD. This study demonstrated that Exendin-4, which is a glucagon-like
      peptide-1 analogue which is used as a therapeutic drug for T2DM, markedly
      antagonized Abeta fragment-induced attenuation of spatial learning and memory
      ability, as indicated by a Morris water maze experiment. In addition, we
      investigated the potential underlying electrophysiological and molecular
      mechanisms. The results indicate that Exendin-4 rescued long-term potentiation
      from Abeta1-42-induced damage in the rat hippocampal CA1 region in vivo, and
      antagonized Abeta1-42-induced reduction of cyclic adenosine monophosphate and
      phosphorylated-cAMP response element-binding protein in rat hippocampal tissue
      using ELISA and western blot analysis, respectively. Thus, the results of the
      present study provide theoretical support for the application of Exendin-4 for
      improving AD.

PMID- 27882093
TI  - Atherosclerotic coronary artery disease: The accuracy of measures to diagnose
      preclinical atherosclerosis.
AB  - Different methods can be used to diagnose early pre-clinical stage
      atherosclerosis. The present study was carried out to evaluate the efficiency of
      these methods. Measures including carotid intima-media thickness (CIMT), pulse
      wave velocity (PWV), and coronary calcium score (CCS) were evalutated for the
      detection of coronary artery disease (CAD). We studied the clinical and
      biochemical profiles of individuals with non-CAD and CAD to assess measures of
      pre-clinical atherosclerosis. The association between CIMT, PWV and CCS on the
      one hand, and the coronary atherosclerosis on the other, was studied. In total,
      150 cases of cardiovascular disease (CVD) participated in the present study and
      were subjected to computed tomographic (CT) coronary angiography to divide them
      into non-CAD (n=100) and CAD (n=50) groups. The patients were also subjected to
      pre-clinical atherosclerosis tests (CIMT, PWV and CCS). CAD patients had higher
      CIMT values on both sides (right side, 0.74+/-0.09 vs. 0.62+/-0.12 mm; left side,
      0.78+/-0.16 vs. 0.64+/-0.19 mm; and average, 0.76+/-0.12 vs. 0.63+/-0.14 mm; all
      P-values <0.01). These patients also had significantly higher brachial-ankle PWV
      (baPWV) on left side (1638.8+/-372.9 vs. 1498.6+/-339.8 cm/sec, P<0.001). The
      overall CCS was significantly increased in CAD patients as compared to the
      patients without CAD (117.8+/-118.6 vs. 8.6+/-18.3, P<0.001). In conclusion, the
      present study showed that among different measures of preclinical
      atherosclerosis, CCS had the best diagnostic accuracy. However, the combination
      of CIMT and baPWV had an excellent negative predictive value for atherosclerotic
      coronary vascular disease.

PMID- 27882092
TI  - The influence of exendin-4 intervention on -obese diabetic mouse blood and the
      pancreatic tissue immune microenvironment.
AB  - The aim of the study was to determine the influence of exendin-4 intervention on
      non-obese diabetic (NOD) mouse blood and the pancreatic tissue immune
      microenvironment. A total of 40 clean NOD mice were used in the study and
      randomly divided into 4 groups (n=10/group). The first group was blank control
      group D with normal saline intervention, and with different doses of exendin,
      i.e.,-4 2, 4 and 8 ug/kg/day. The three remaining groups were: i) Low-dose group
      A; ii) medium-dose group B; and iii) high-dose group C. Mice in the four groups
      went through intervention for 8 weeks. Their mass and blood glucose levels were
      tested each week. After 8 weeks, the mice were sacrificed, and mouse serum
      samples were reserved. The ELISA method was used to test peripheral blood (PB),
      IL-2, IFN-gamma and IL-10 levels. Pancreatic samples were created.
      Immunohistochemistry was used to observe the infiltration degree of mouse
      pancreatitis and the local expression state of pancreatic IL-10. Mouse pancreatic
      tissues were suspended in pancreatic cell suspension. Flow cytometry was used to
      test the state of T-cell subsets CD4 and CD25. Mouse pancreatitis in control
      group D was mainly at grade 2and 3. Under a light microscope, it was observed
      that pancreatic cell morphology was in disorder, and the size and quantity of the
      pancreas was small. Mouse pancreatitis in the exendin-4 low-dose group A, medium
      dose group B and high-dose group C was mainly at grade 0 and 1. Under a light
      microscope, it was observed that pancreatic cell morphology improved, the
      infiltration degree of lymphocyte was improved and pancreatic islet size was
      restored somewhat. Additionally, a few brownish granules were identified within
      the pancreatic sample cells in control group D. There were many brownish granules
      with deep color within the pancreatic sample cells in exendin-4 low-dose group A,
      medium-dose group B and high-dose group C. IL-10 immunohistochemistry scores in
      the low-dose group A, medium-dose group B and high-dose group C were 3.82+/-0.72,
      4.34+/-0.86 and 4.81+/-0.94, respectively, and were higher than the score of
      2.25+/-0.63 in control group D. CD4+CD25+T-cell proportions in mouse pancreatic
      tissues of low-dose group A, medium-dose group B and high-dose group C were 5.31,
      5.53 and 5.74%, respectively, which were higher than that of the CD4+CD25+T-cell
      proportion (1.62% in control group D). The CD4+CD25high T-cell proportion in
      CD4+T-cells in group A, B and C increased. Compared with control group D, serum
      IL-10 levels in the exendin-4 low-dose group A, medium-dose group B and high-dose
      group C increased (P<0.05), while levels of IL-2 and IFN-gamma decreased
      (P<0.05). Additionally, the difference of serum IL-10, IL-2 and IFN-gamma levels
      in the low-dose group A, medium-dose group B and high-dose group C was of
      statistical significance (P<0.05). Exendin-4 intervention can increase quantities
      of CD4 and CD8+T cells in NOD mouse pancreases, with PB IL-10 expression and
      local expression of IL-10 in pancreatic tissues. It also can inhibit the
      expression of serum IL-2 and IFN-gamma, regulate the organism immune
      microenvironment and prevent diabetes. CD4+CD25high T cells increase in NOD tumor
      infiltration lymphocytes mediated by exendin-4 intervention, which may be related
      to the fact that exendin-4 inhibits the lethal effect of CD8+T cells through
      contact among cells and eventually exerts immunosuppressive effect.

PMID- 27882094
TI  - The protective and hemodynamic effects of dexmedetomidine on hypertensive
      cerebral hemorrhage patients in the perioperative period.
AB  - The aim of the present study was to analyze the protective and hemodynamic
      effects of dexmedetomidine in hypertensive cerebral hemorrhage (HCH) patients
      during perioperative period. In total, 50 HCH patients were selected and randomly
      divided into two groups, one group was administered with dexmedetomidine and the
      other groups with midazolam. The mean arterial pressure (MAP), heart rate (HR)
      and blood oxygen saturation (SpO2) were monitored in the two groups of patients
      before and during the operation. The MAP, HR, SpO2 and PETCO2 recorded 5 min
      after admission into the operation room was considered T1, the same parameters
      recorded 10 min after drug administration were considered T2, just after starting
      the operation were considered T3 and 30 min after start of operation were
      considered T4. The preoperative sedation and analgesia were evaluated by the
      Ramsay scoring method and the neuron-specific enolase (NSE) and S100 protein
      (S100beta) were estimated using ELISA. The patients of the midazolam group
      experienced mild respiratory depression during the period of sedation. Levels of,
      MAP, HR and PETCO2 were significantly increased whereas SPO2 was decreased
      (P<0.05). The MAP, HR, SPO2 and PETCO2 were stable during the period of sedation
      (P>0.05). The plasma concentrations of epinephrine and norepinephrine at T1 were
      similar in the two groups (P>0.05), but decreased after drug administration. This
      decrease was more prominent in the dexmedetomidine group patients (P<0.05) than
      midazolam group patients. The epinephrine and norepinephrine concentrations just
      after starting operation (T3) were higher than the basal level (T1) in the
      midazolam group, but close to the basal level in the dexmedetomidine group
      (P<0.05). The serum concentration of NSE and S100beta in the two groups showed no
      difference (P>0.05) at the end of operation (T5), but after 24 h of operation
      (T7) NSE and S100beta in the dexmedetomidine group were significantly lower
      compared to the midazolam group (P<0.05). In conclusion, the administration of
      dexmedetomidine for patients with HCH during perioperative period is safe and
      serves as an effective sedative, without causing respiratory depression and does
      not influence stable haemodynamics with certain brain protective effect.

PMID- 27882095
TI  - Effect of acupoint catgut embedding therapy combined with Chinese medicine for
      nourishing the kidneys and promoting blood circulation and improving blood
      glucose and lipid levels as well as the pregnancy rate in obese PCOS patients
      with infertility.
AB  - In this study, we explored the effect of acupoint catgut embedding combined with
      Chinese medicine for nourishing kidney and promoting blood circulation as well as
      improving the glucose and lipid levels and pregnancy rate in obese polycystic
      ovary syndrome (PCOS) patients with infertility. A total of 62 obese patients
      with PCOS were randomly divided into three groups, 21 of whom were treated with
      acupoint catgut embedding combined with Chinese medicine, another 21 with catgut
      embedding therapy, and 20 only with Chinese medicine. We compared the improvement
      of clinical symptoms and the glucose and lipid levels in the three groups three
      months after surgery. We found that the effective rate of obesity treatment, body
      mass index and waist-to-hip ratio of acupuncture-drug group and catgut embedding
      group were significantly lower than those of the Chinese medicine group (P<0.05).
      A comparison between the acupuncture-drug group and catgut embedding group was
      not statistically significant (P>0.05). The triglyceride (TG) and high-density
      lipoprotein cholesterol (HDL) levels of the three groups were significantly
      decreased and increased, respectively, following treatment, with the total
      cholesterol (TC) level being decreased significantly only in the acupuncture-drug
      group (P<0.05), and the LDL level showing no significant difference (P>0.05). The
      fast insulins, HOMA-IR, TG, TC levels and periodic cancellation rate of the
      acupuncture-drug group was significantly reduced compared to those of the catgut
      embedding group and Chinese medicine group after treatment, whereas the HDL
      levels, periodic ovulation rate and clinical pregnancy rate were higher (P<0.05).
      However, a comparison between Chinese medicine group and catgut embedding group
      was not statistically significant (P>0.05). The incidence rate of luteinized
      unruptured follicle and ovarian hyper-stimulation syndrome of the three groups
      showed no statistical difference (P>0.05). In conclusion, the study has shown
      that acupoint catgut embedding therapy combined with Chinese medicine for
      nourishing the kidneys and promoting blood circulation and improving blood
      glucose and lipid levels as well as the pregnancy rate in obese PCOS patients
      with infertility is useful.

PMID- 27882096
TI  - Association between clusterin gene polymorphism rs11136000 and late-onset
      Alzheimer's disease susceptibility: A review and meta-analysis of case-control
      studies.
AB  - The present study aimed to evaluate the association between rs11136000 in
      clusterin (CLU) and late-onset Alzheimer's disease (LOAD) by meta-analysis.
      Several databases including PubMed, EMbase, CBMdisc and CMCC were searched for
      relevant case-control studies based on defined selection criteria. Odds ratios
      (OR) and 95% confidence interval (CI) of the rs11136000 genotype and allele
      distribution were analyzed with RevMan and Stata software. The control population
      and heterogeneity between populations were examined in the selected studies using
      the Hardy-Weinberg equilibrium. Overall OR among the frequencies of the genotype
      and allele in both patients with AD and controls was estimated using fixed or
      random effect models. The summary of the OR and 95% CI were then analyzed to
      obtain the effects across the studies. Publication bias was examined using a
      funnel plot, Egger's test and Begg's test, and a Fail-safe Number (Nfs). A total
      of 20 reports were used. The summary OR for studies in the Caucasian population
      with a frequency of TT+TC/CC genotype and T/C allele at rs11136000 locus in CLU
      were 0.79 (95% CI, 0.73-0.86; P<0.00001) and 0.87 (95% CI, 0.85-0.90; P<0.00001).
      The summary OR for the studies conducted in the Asian population were 0.90 (95%
      CI, 0.81-0.99; P=0.04) and 0.87 (95% CI, 0.81-0.93; P<0.0001). The summary OR in
      other mixed ethnic groups with regards to the frequency of T/C allele was 0.82
      (95% CI, 0.68-0.99; P=0.04). These results demonstrated the presence of a
      statistically significant difference in LOAD susceptibility between individuals
      with the T allele CLU rs11136000 polymorphism and those without. The studies
      conducted in populations of African descent or Hispanics showed no statistically
      significant difference. Negligible publication bias was present, with Nfs being
      750.604. In summary, polymorphism rs11136000 in the CLU gene may contribute to
      susceptibility to LOAD, and the presence of the T allele may reduce the risk of
      LOAD in Caucasian and Asian populations. However, no definitive association was
      found between the presence of the CLU rs11136000 polymorphism and LOAD in
      populations of African or Hispanic descent.

PMID- 27882097
TI  - Effect of a paclitaxel-eluting metallic stent on rabbit esophagus.
AB  - The use of self-expanding metallic stents (SEMS) is the current treatment of
      choice for malignant gastrointestinal obstructions. A paclitaxel-eluting metallic
      SEMS (PEMS) may have an antitumor effect on esophageal tissue. PEMS with 10%
      paclitaxel or conventional SEMS were inserted into the lower esophagus of
      rabbits. Following the insertion of the stents for 1, 2, 4 and 6 weeks, the
      rabbits were sacrificed and the status of the stent insertion was examined, as
      well as any macroscopic or microscopic mucosal changes in the esophageal tissue.
      All the rabbits survived until death without any complications. No migration
      following stent insertion occurred. The number of cases with proximal obstruction
      increased in a time-dependent manner, and no significant difference was observed
      between the two groups. Gross histological examination showed similar tissue
      reaction to the stents at 1, 2 and 4 weeks, and inflammatory cell infiltrating
      was higher in the SEMS group at 1 and 2 weeks. However, inflammatory cell
      infiltration was markedly higher in the PEMS group at 4 and 6 weeks. Food-intake
      and weight were similar in the two groups. The results of the present study
      demonstrated that PEMS may serve as a safe alternative treatment strategy for
      esophageal obstruction. Furthermore, PEMS may inhibit the tumor growth of the
      esophageal wall through inflammatory infiltration and targeted drug delivery. A
      tumor model will be required in the future for evaluating the prognosis of
      patients with advanced esophageal carcinoma.

PMID- 27882098
TI  - Validation of a novel sleep-monitoring system for diagnosing obstructive sleep
      apnea: A comparison with polysomnography.
AB  - Overnight polysomnography (PSG) is currently the gold standard for diagnosing
      obstructive sleep apnea (OSA); however, it is time-consuming, expensive and
      uncomfortable for the patient. A micromovement sensitive mattress (MSM) sleep
      monitoring system was developed as an alternative to PSG, however, there has yet
      to be a study verifying the accuracy of diagnosing OSA with this device.
      Therefore, the present study assessed the validity of the MSM sleep-monitoring
      system. Chinese Han participants who were suspected of having OSA were recruited
      between June 2013 and June 2014. The MSM sleep-monitoring system and PSG were
      utilized simultaneously overnight on each subject. The apnea-hypopnea index (AHI)
      was measured by the MSM sleep-monitoring system (AHIMSM) and compared with that
      determined by PSG (AHIPSG), revealing a significant correlation between the two
      values (r=0.97, P<0.001). Bland-Altman plots also indicated good agreement (97%)
      between MSM and PSG. Using an AHIPSG cut-off of >=5, >=15 and >=30 events/h, the
      sensitivity (specificity) of detecting an AHIMSM of >=5, >=15, and >=30 events/h
      were 94.9 (100%), 89.9 (96.9%) and 90.3% (94.9%), respectively. The areas under
      the receiver operating characteristic curve, which were used to differentiate an
      AHIPSG of >=5, >=15 and >=30 events/h in clinically diagnosed OSA, were 0.984,
      0.982 and 0.980, respectively. Thus, the MSM sleeping system may accurately
      diagnose OSA in the Chinese Han population. Further community-based studies with
      larger sample sizes are warranted to confirm the validity of this MSM sleeping
      system.

PMID- 27882099
TI  - Correlations of smoking with cumulative total dust exposure and cumulative
      abnormal rate of pulmonary function in coal-mine workers.
AB  - The present study aimed to investigate the correlation of smoking with cumulative
      total dust exposure (CTE) and cumulative abnormal rate of pulmonary function in
      coal-mine workers. A total of 376 coal-mine workers were recruited as the
      observational group, while 179 healthy workers in other industries were selected
      as the control group. All the workers underwent pulmonary function testing to
      determine their forced vital capacity (FVC), forced expiratory volume in 1 second
      (FEV1) and FEV1/FVC, in order to compare the abnormal pulmonary function between
      the two groups. A markedly higher number of smokers was observed in the
      observational group (200/376, 53.19%) when compared with the control group
      (72/179, 40.22%). In smokers, the abnormal rate of pulmonary function in the
      observational group (102/200, 51.00%) was evidently higher compared with that in
      the control group (19/72, 26.39%), whereas no significant difference was detected
      between the two groups of non-smokers (P=0.077). In addition, FVC, FEV1 and
      FEV1/FVC of the observational group were found to be lower compared with those in
      the control group, in both the smoking and non-smoking subgroups. In the smoking
      subgroup, FVC and FEV1 in subjects working at the coal mine for different number
      of years showed significant differences (all P<0.05), whereas comparison of
      FEV1/FVC in workers with different working durations showed no significant
      difference (P=0.169). However, in the non-smoking subgroup, the comparison of
      FVC, FEV1 and FEV1/FVC in different working duration groups also showed no
      significant difference (all P>0.05). Furthermore, FVC, FEV1 and FEV1/FVC in
      smoking coal-mine workers were negatively correlated with the dust-exposure
      working duration (P<0.05). CTE was also positively correlated with cumulative
      abnormal rate of pulmonary function in the smoking and non-smoking subgroups,
      while FEV1 was negatively correlated with CTE in the smoking subgroup (P=0.009).
      In conclusion, smoking is an important risk factor for the damage of pulmonary
      function in coal-mine workers, and it is positively correlated with dust-exposure
      time and CTE in these individuals.

PMID- 27882100
TI  - Optimization and validation of the protocol used to analyze the taste of
      traditional Chinese medicines using an electronic tongue.
AB  - Tools to define the active ingredients and flavors of Traditional Chinese
      Medicines (TCMs) are limited by long analysis times, complex sample preparation
      and a lack of multiplexed analysis. The aim of the present study was to optimize
      and validate an electronic tongue (E-tongue) methodology to analyze the
      bitterness of TCMs. To test the protocol, 35 different TCM concoctions were
      measured using an E-tongue, and seven replicate measurements of each sample were
      taken to evaluate reproducibility and precision. E-tongue sensor information was
      identified and classified using analysis approaches including least squares
      support vector machine (LS-SVM), support vector machine (SVM), discriminant
      analysis (DA) and partial least squares (PLS). A benefit of this analytical
      protocol was that the analysis of a single sample took <15 min for all seven
      sensors. The results identified that the LS-SVM approach provided the best
      bitterness classification accuracy (binary classification accuracy, 100%; ternary
      classification accuracy, 89.66%). The E-tongue protocol developed showed good
      reproducibility and high precision within a 6 h measurement cycle. To the best of
      our knowledge, this is the first study of an E-tongue being applied to assay the
      bitterness of TCMs. This approach could be applied in the classification of the
      taste of TCMs, and serve important roles in other fields, including foods and
      beverages.

PMID- 27882101
TI  - Effects of dexpanthenol on acetic acid-induced colitis in rats.
AB  - While the pathogenesis of acetic acid (AA)-induced colitis is unclear, reactive
      oxygen species are considered to have a significant effect. The aim of the
      present study was to elucidate the therapeutic potential of dexpanthenol (Dxp) on
      the amelioration of colitis in rats. Group I (n=8; control group) was
      intrarectally administered 1 ml saline solution (0.9%); group II [n=8; AA] was
      administered 4% AA into the colon via the rectum as a single dose for three
      consecutive days; group III (n=8; AA + Dxp) was administered AA at the same
      dosage as group II from day 4, and a single dose of Dxp was administered
      intraperitoneally; and group IV (n=8; Dxp) was administered Dxp similarly to
      Group III. Oxidative stress and colonic damage were assessed via biochemical and
      histologic examination methods. AA treatment led to an increase in oxidative
      parameters and a decrease in antioxidant systems. Histopathological examination
      showed that AA treatment caused tissue injury and increased caspase-3 activity in
      the distal colon and triggered apoptosis. Dxp treatment caused biochemical and
      histopathological improvements, indicating that Dxp may have an anti-oxidant
      effect in colitis; therefore, Dxp may be a potential therapeutic agent for the
      amelioration of IBD.

PMID- 27882102
TI  - Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus
      infected cervical cancer cells.
AB  - In order to evaluate the potential application value of cidofovir (CDV) in the
      prevention of human papillomavirus (HPV) infection and treatment of cervical
      cancer, the inhibitory effect of CDV on the proliferation of HPV 18-positive HeLa
      cells in cervical cancer was preliminarily investigated, using cisplatin (DDP) as
      a positive control. An MTT assay was used to analyze the effects of CDV and DDP
      on HeLa cell proliferation. In addition, clone formation assay and Giemsa
      staining were used to examine the extent of HeLa cell apoptosis caused by CDV and
      DDP. Flow cytometry was also used to detect the shape and size of apoptotic cells
      following propidium iodide staining, while western blot analysis identified the
      expression levels of of E6 and p53 proteins in HeLa cells. A cell climbing
      immunofluorescence technique was used to locate the subcellular position of p53
      in HeLa cells. The results demonstrated that CDV and DDP inhibited the
      proliferation of HeLa cells in a concentration- and time-dependent manner. Flow
      cytometry showed that CDV and DDP treatments resulted in cell arrest in the S
      phase, and triggered programmed cell death. Furthermore, western blot analysis
      revealed that CDV and DDP inhibited E6 protein expression and activated p53
      expression in HeLa cells. Finally, the immunofluorescence results indicated that
      CDV and DDP inhibited the nuclear export of p53 by E6 protein, which is required
      for degradation of endogenous p53 by MDM2 and human papilloma virus E6. In
      conclusion, CDV and DDP inhibited HeLa cell proliferation in a concentration- and
      time-dependent manner, reduced the expression of E6 protein, and reinstated p53
      protein activity. Thus, CDV regulates cell cycle arrest and apoptosis, and may be
      a potential cervical cancer therapeutic strategy.

PMID- 27882103
TI  - Identification of proteins suppressing the functions of oncogenic phosphatase of
      regenerating liver 1 and 3.
AB  - The phosphatase of regenerating liver (PRL) family, including PRL-1, PRL-2, and
      PRL-3, comprises protein tyrosine phosphatases whose deregulation is associated
      with the tumorigenesis and metastasis of many types of cancer. However, the
      underlying mechanism is poorly understood. In this study, aiming to increase
      understanding of the molecular mechanisms underlying the functions of PRL-1 and
      PRL-3, a yeast two-hybrid system was employed to screen for their interacting
      proteins. Alignment with the NCBI BLAST database revealed 12 interactive
      proteins: Synaptic nuclear envelope protein 2, emerin, mannose 6-phosphate
      receptor-binding protein 1, low-density lipoprotein receptor-related protein 10,
      Rab acceptor 1, tumor protein D52-like 2, selectin P ligand (SELPLG), guanylate
      binding protein 1, transmembrane and ubiquitin-like domain-containing 2,
      NADH:ubiquinone oxidoreductase subunit B8, syndecan 4 and FK506-binding protein 8
      (FKBP8). These proteins are associated with cell proliferation, apoptosis, immune
      response, cell fate specification and metabolic process in biological process
      categories, and involved in various signaling pathways, including Alzheimer's
      disease, Parkinson's disease, Huntington's disease, hypertrophic cardiomyopathy
      and cell adhesion molecules. Interactions of PRL-1 with the prey proteins SELPLG
      and FKBP8 were confirmed by immunoprecipitation or immunostaining. Furthermore,
      SELPLG and FKBP8 suppressed PRL-1- or PRL-3-mediated p53 activity. Identification
      of the proteins interacting with PRL family proteins may provide valuable
      information to better understand the mechanism of PRL-mediated signal
      transduction in cancer and other diverse diseases.

PMID- 27882104
TI  - Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to
      severe ulcerative colitis.
AB  - One of the primary targets of the clinical treatment of ulcerative colitis (UC)
      is to repair the damaged colonic mucosa. Mesenchymal stem cells (MSCs) have
      therapeutic potential in regenerative medicine due to their differentiation
      capacity and their secretion of numerous bioactive molecules. The present study
      describes a clinical trial (trial registration no. NCT01221428) investigating the
      safety and therapeutic effect of MSCs derived from human umbilical cord on
      moderate to severe UC. Thirty-four patients with UC were included in group I and
      treated with MSC infusion in addition to the base treatment, and thirty-six
      patients were in group II and treated with normal saline in addition to the base
      treatment. One month after therapy, 30/36 patients in group I showed good
      response, and diffuse and deep ulcer formation and severe inflammatory mucosa
      were improved markedly. During the follow up, the median Mayo score and histology
      score in group I were decreased while IBDQ scores were significantly improved
      compared with before treatment and group II (P<0.05). Compared with group II,
      there were no evident adverse reactions after MSC infusion in any of the patients
      in group I, and no chronic side effects or lingering effects appeared during the
      follow-up period. In conclusion, MSC infusion might be a useful and safe therapy
      for treating UC.

PMID- 27882106
TI  - Evaluation of CRRT effects on pyemic secondary AKI by serum cartilage
      glycoprotein 39 and Annexin A1.
AB  - The aim of the present study was to examine the effects of continuous renal
      replacement therapy (CRRT) on pyemic secondary acute kidney injury (AKI) by serum
      cartilage glycoprotein 39 (YKL-40) and Annexin A1. From October, 2013 to October,
      2015, 45 pyemic secondary AKI cases and 40 pyemic non-secondary AKI cases were
      selected for the present study. There were also 35 cases of physical examination
      volunteers. The serum YKL-40 and Annexin A1 levels were compared. CRRT was
      applied to pyemic secondary AKI patients and based on the obtained results the
      patients were divided into the success and failure groups. YKL-40, Annexin A1, hs
      CRP, creatinine and urea nitrogen levels after 1, 6, 12, 24, 48 and 72 h of AKI
      were measured. The YKL-40 and Annexin A1 levels in the pyemic secondary AKI group
      were significantly higher than those in other two groups and differences were
      statistically significant (P<0.05). There was no statistically significant
      difference regarding time period for applying CRRT in the success and failure
      groups (P>0.05). The peak level of YKL-40 and Annexin A1 in the success group
      decreased more rapidly compared to the failure group and the difference was
      statistically significant (P<0.05). When the differences in creatinine and urea
      nitrogen levels at different time points were compared between the success and
      failure groups, no statistical significance was observed (P>0.05). However, the
      success group showed a significantly lower level compared to the failure group at
      72 h. Comparisons for other time periods showed no statistical significance
      (P>0.05). Thus, the serum cartilage glycoprotein 39 and Annexin A1 level were
      able to predict the clinical effects of CRRT on pyemic secondary AKI.

PMID- 27882105
TI  - A pilot study of perioperative esmolol for myocardial protection during on-pump
      cardiac surgery.
AB  - The protective effects of preprocedural esmolol on myocardial injury and
      hemodynamics have not, to date, been investigated in patients who were scheduled
      for cardiac surgeries under a cardiopulmonary bypass (CPB). A pilot randomized
      controlled trial was performed at The First Affiliated Hospital of Dalian Medical
      University (Dalian, China). Patients scheduled for elective open-heart surgeries
      under CBP were included, and were randomized to esmolol and control groups. For
      patients in the esmolol groups, intravenous esmolol (70 ug/kg/min) was
      administered at the time of incision until CPB was performed. For patients
      assigned to the control group, equal volumes of 0.9% saline were administered.
      Markers of myocardial injury and hemodynamic parameters were observed until 12 h
      post surgery. A total of 24 patients were included in the present study. No
      significant differences in hemodynamic parameters, including the central venous
      pressure and heart rate, were detected between patients in the two groups during
      the perioperative period or within the first 12 h post-surgery (P>0.05), except
      for the mean arterial pressure, which was higher in the esmolol group compared
      with the control group at 5 and 12 h post-surgery (P<0.05). However, the serum
      level of cardiac troponin I was higher in patients of the control group compared
      with those of the esmolol group during the preoperative period (P<0.05). Although
      creatinine kinase was significantly different at T2 between the two groups, its
      MB isoenzyme was not significantly different between the groups (P>0.05). In
      addition, administration of esmolol was not associated with an increased risk for
      severe complications and adverse events in these patients. In conclusion,
      preoperative esmolol may be an effective and safe measure of myocardial
      protection for patients who undergo elective cardiac surgeries under CBP.

PMID- 27882107
TI  - Effects of sitagliptin as initial therapy in newly diagnosed elderly type 2
      diabetics: A randomized controlled study.
AB  - The objective of this study was to investigate the characteristics of blood
      glycemic excursion, incretins and pancreatic hormone secretion in elderly people
      with newly diagnosed type 2 diabetes mellitus (T2DM) and to study the effects of
      sitagliptin on glycemic excursion in these subjects. A total of 129 newly
      diagnosed T2DM patients were enrolled in the study from March 2012 to August
      2013. Clinical data, serum incretin, pancreatic hormone and continuous glucose
      monitoring data were collected. Among these subjects, elderly patients (NEDM)
      randomly received metformin combined with sitagliptin phosphate or glimepiride
      for 24 weeks. The blood glucose, glycosylated hemoglobin A1c (GHbA1c), serum
      incretins and pancreatic hormone levels were determined. During the oral glucose
      tolerance test (OGTT), 30 min insulin and C-peptide levels, 120 min insulin
      levels and ratio of the increases of insulin and blood glucose levels after 30
      min of sugar loading (?Ins30/?Glu30) were significantly lower in elderly patients
      than in middle-aged patients (P<0.05). In addition, the glucagon elevation at 30
      min was higher and the glucagon-like peptide-1 (GLP-1) at 30 min was lower in the
      elderly patients (P<0.05). Glucose excursion indices, including the standard
      deviation of the average blood glucose, intraday mean average glucose excursions
      (MAGE), and mean of daily differences (MODD), were significantly higher in the
      elderly patients (P<0.05). During the OGTT, insulin, C-peptide and ?Ins30/?Glu30
      results at 30 min and GLP-1 levels at 120 min in NEDM subjects were significantly
      increased (P<0.05) and glucagon levels at 30 min was significantly lower after
      sitagliptin treatment (P<0.05) compared with glimepiride. Moreover, MAGE and MODD
      were significantly lower in the sitagliptin group after treatment compared to
      those in the glimepiride group (P<0.05). No severe hypoglycemia or cardiovascular
      diseases were observed. Strong blood glucose excursions occur in elderly patients
      with newly diagnosed T2DM. Sitagliptin phosphate combined with metformin
      effectively and safely improves glycemic excursion and carbohydrate metabolism in
      NEDM patients by promoting the first phase of insulin and incretin secretion and
      inhibiting glucagon secretion of.

PMID- 27882108
TI  - Effects of piezosurgery in accelerating the movement of orthodontic alveolar bone
      tooth of rats and the expression mechanism of BMP-2.
AB  - The aim of the study was to investigate the effects of piezosurgery in
      accelerating the movement of orthodontic alveolar bone tooth of rats and the
      expression mechanism of bone morphogenetic protein-2 (BMP-2). Adult male Wistar
      rats (n=30), with an age range of 14-15 weeks, and an average weight of 250+/-16
      g were used. The animals were randomly divided into the control and observation
      groups. The rats in the control group were injected with 25-dihydroxyvitamin
      (1,25-dihydroxycholecalciferol) into their dental ligament. The rats in the
      observation group were placed with an orthodontic device between the first molar
      and central incisor in the maxillary. On the first day after animal treatment,
      piezosurgery stimulation was performed on the first molar in maxillary. The
      changes of the movement distance of the first molar and gum surface temperature
      on days 1, 3, 5, 7 and 14 were then compared. Immunohistochemical staining was
      performed to detect the expression of BMP-2 of periodontal tissue in the tension
      side of the first molar. Tooth movement distance in the observation group on days
      5, 7 and 14 was significantly longer than that in the control group (p<0.05). The
      gum surface temperature of the observation group was elevated to some extent,
      peaking after 20 min. BMP-2 mRNA and protein levels in the observation group were
      significantly higher than those of the control group at days 3, 5, 7 and 14
      (p<0.05). In conclusion, piezosurgery may significantly accelerate the movement
      of orthodontic alveolar bone tooth of rats and be associated with an increasing
      BMP-2 expression.

PMID- 27882109
TI  - Excisional keratectomy combined with focal cryotherapy and amniotic membrane
      inlay for recalcitrant filamentary fungal keratitis: A retrospective comparative
      clinical data analysis.
AB  - The aim of the present study was to investigate the efficacy of a novel surgical
      intervention, excisional keratectomy combined with focal cryotherapy and amniotic
      membrane inlay (EKCAI), for the treatment of recalcitrant filamentary fungal
      keratitis. A retrospective analysis was performed of patients who underwent
      excisional keratectomy combined with conjunctival flap inlay (EKCFI), EKCAI or
      therapeutic penetrating keratoplasty (TPK) from January 2006 to January 2011.
      Recalcitrance was determined as being unresponsive to standard medical antifungal
      therapy for at >=1 week. Outcome measures among the three intervention modalities
      were compared. A total of 128 patients had a follow-up of >=1 year after the
      primary intervention. The success rates of interventions at 1-year follow-up were
      58.33% in the EKCFI group, 88.37% in the EKCAI group and 93.44% in the TPK group
      (P<0.0002). The preoperative visual acuity of the three groups were similar
      (P=0.6458), while the postoperative best-corrected visual acuity (BCVA) of
      patients without recurrence was significantly different among the three groups 3
      months after surgery. The best postoperative BCVA was found in the TPK group,
      while the worst was in the EKCFI group. In conclusion, EKCAI does not require
      donor cornea, is straightforward surgically, and has a favorable success rate
      compared with EKCFI.

PMID- 27882110
TI  - Intermittent fasting is neuroprotective in focal cerebral ischemia by minimizing
      autophagic flux disturbance and inhibiting apoptosis.
AB  - Previous studies have demonstrated that autophagy induced by caloric restriction
      (CR) is neuroprotective against cerebral ischemia. However, it has not been
      determined whether intermittent fasting (IF), a variation of CR, can exert
      autophagy-related neuroprotection against cerebral ischemia. Therefore, the
      neuroprotective effect of IF was evaluated over the course of two weeks in a rat
      model of focal cerebral ischemia, which was induced by middle cerebral artery
      occlusion and reperfusion (MCAO/R). Specifically, the role of autophagy
      modulation as a potential underlying mechanism for this phenomenon was
      investigated. It was demonstrated that IF reduced infarct volume and brain edema,
      improved neurobehavioral deficits, and rescued neuronal loss after MCAO/R.
      Furthermore, neuronal apoptosis was decreased by IF in the rat cortex. An
      increase in the number of autophagosomes (APs) was demonstrated in the cortices
      of IF-treated rats, using immunofluorescence staining and transmission electron
      microscopy. Using immunoblots, an IF-induced increase was detected in microtubule
      associated protein 1 light chain 3 (LC3)-II, Rab7, and cathepsin D protein
      levels, which corroborated previous morphological studies. Notably, IF reduced
      the accumulation of APs and p62, demonstrating that IF attenuated the MCAO/R
      induced disturbance of autophagic flux in neurons. The findings of the present
      study suggest that IF-induced neuroprotection in focal cerebral ischemia is due,
      at least in part, to the minimization of autophagic flux disturbance and
      inhibition of apoptosis.

PMID- 27882111
TI  - Complete prefrontal lobe isolation surgery for recurrent epilepsy: A case report.
AB  - Epileptogenic focus resection is less effective for the treatment of frontal lobe
      epilepsy compared with temporal lobe epilepsy. However, there is currently a lack
      of effective therapeutic options for patients with frontal lobe epilepsy who are
      unsuitable for epileptogenic focus resection (such patients with epileptogenic
      foci in one frontal lobe in which the precise epileptic foci cannot be
      determined), or who experience recurrent epilepsy following epileptogenic focus
      resection. The present study reports a patient with frontal lobe epilepsy who
      underwent successful frontal lobe isolation surgery following a previous
      unsuccessful epileptogenic focus resection surgery. To ensure complete isolation
      of the prefrontal lobe, the surgery included division of the anterior commissure
      and the anterior part of the corpus callosum. The patient was followed-up for 16
      months. Although the follow-up electroencephalogram presented a number of sharp
      waves on the affected side, the patient did not experience any seizures. The
      results suggest that prefrontal lobe isolation is an effective method of treating
      frontal lobe epilepsy, as division of the anterior commissure and the anterior
      part of the corpus callosum ensures disconnection of the prefrontal lobe from
      other regions of the brain.

PMID- 27882112
TI  - Diagnostic value of high-frequency ultrasound and magnetic resonance imaging in
      early rheumatoid arthritis.
AB  - Early diagnosis and management improve the outcome of patients with rheumatoid
      arthritis (RA). The present study explored the application of high-frequency
      ultrasound (US) and magnetic resonance imaging (MRI) in the detection of early
      RA. Thirty-nine patients (20 males and 19 females) diagnosed with early RA were
      enrolled in the study. A total of 1,248 positions, including 858 hand joints and
      390 tendons, were examined by high-frequency US and MRI to evaluate the presence
      of bone erosion, bone marrow edema (BME), synovial proliferation, joint effusion,
      tendinitis and tendon sheath edema. The imaging results of the above
      abnormalities, detected by US, were compared with those identified using MRI. No
      statistically significant overall changes were observed between high-frequency US
      and MRI in detecting bone erosion [44 (5.1%) vs. 35 (4.1%), respectively;
      P>0.05], tendinitis [18 (4.6%) vs. 14 (1.5%), respectively; P>0.05] and tendon
      sheath edema [37 (9.5%) vs. 30 (7.7%), respectively; P>0.05]. Significant
      differences were observed between high-frequency US and MRI with regards to the
      detection of synovial proliferation [132 (15.4%) vs. 66 (7.7%), respectively;
      P<0.05] and joint effusion [89 (10.4%) vs. 52 (6.1%), respectively; P<0.05]. In
      addition, significant differences were identified between the detection of BME
      using MRI compared with high-frequency US (5.5 vs. 0%, respectively; P<0.05). MRI
      and high-frequency US of the dominant hand and wrist joints were comparably
      sensitive to bone erosion, tendinitis and tendon sheath edema. However, MRI was
      more sensitive in detecting bone marrow edema in early RA, while US was more
      sensitive in the evaluation of joint effusion and synovial proliferation. In
      conclusion, US and MRI are promising for the detection and diagnosis of
      inflammatory activity in patients with RA.

PMID- 27882113
TI  - Peripheral neuropathy outcomes and efficacy of subcutaneous bortezomib when
      combined with thalidomide and dexamethasone in the treatment of multiple myeloma.
AB  - Due to the safety, convenience and efficacy of subcutaneous administration of
      bortezomib (scBor), it is becoming increasingly common to treat multiple myeloma
      (MM) using this treatment method. The current retrospective study suggested a
      lower incidence of peripheral neuropathy (PN) outcomes and superior efficacy
      following treatment with scBor combined with thalidomide and dexamethasone (VTD)
      in MM when compared with intravenous Bor (ivBor) treatment. The data of 81
      patients from the Affiliated Hospital of Nantong University between September
      2011 and February 2014 were analyzed, including 37 scBor and 44 ivBor patients
      administered a median (range) of 5.5 (3-8) and 6 (3-10) chemotherapy cycles,
      respectively. Adverse events (AEs) were assessed according to the National Cancer
      Institute (NCI) Common Terminology Criteria for AEs, and response and progression
      were assessed by the International Myeloma Working Group criteria. Evidence of
      histopathology using transmission electron microscopy (TEM) was obtained from an
      in vivo model of adult Sprague Dawley (SD) rats. Following bortezomib-based VTD
      chemotherapy, patients had achieved very good partial remission or demonstrated
      no significant difference between the scBor and ivBor treatment groups (75.6 vs.
      84.1%, respectively; P=0.350). The 1-year progression-free survival (83.8 vs.
      84.1%, scBor vs. ivBor; P=0.921) and 1-year overall survival (OS) (91.9 vs.
      90.9%, respectively; P=0.926) were also similar. PN rates of all the NCI grades
      were 51.3 and 61.3% (P=0.371); grade >=2, 35.1 and 56.8% (P=0.052); and grade
      >=3, 32.7 and 20.5% (P=0.015) in the subcutaneous and intravenous treatment
      groups, respectively, which suggests that severe PN may be less common following
      scBor treatment. There were no severe injection site reactions in the scBor
      treated group. The incidence of adverse events were comparable between the two
      groups, including thrombocytopenia, anemia, fatigue and gastrointestinal symptoms
      such as nausea and vomiting. Furthermore, TEM images of the SD rat sciatic nerves
      revealed that all rats suffered PN to varying degrees, except the control group,
      and that the PN of ivBor-treated rats (in the presence and the absence of
      thalidomide) was more severe than that of scBor-treated rats. It was concluded
      that a subcutaneous dose of bortezomib of 1.3 mg/m2 may result in a lower
      incidence and severity of PN, with equivalent efficacy, as a component of
      combination VTD chemotherapy.

PMID- 27882114
TI  - APC2 and CYP1B1 methylation changes in the bone marrow of acute myeloid leukemia
      patients during chemotherapy.
AB  - Aberrant promoter DNA methylation is a major mechanism of leukemogenesis in
      hematologic malignancies, including acute myeloid leukemia (AML). However, the
      association between promoter methylation with chemotherapeutic outcomes remains
      unknown. In the present study, bone marrow samples were collected prior to and
      following chemotherapy in 30 AML patients. Methylation-specific polymerase chain
      reaction technology was used to examine the promoter methylation status of
      adenomatous polyposis col 2 (APC2) and cytochrome P450 family 1 subfamily B
      polypeptide 1 (CYP1B1). The results revealed no change in the methylation status
      of the APC2 promoter in patients following various chemotherapy regimens.
      However, the methylation status of the CYP1B1 promoter changed in response to 6
      different chemotherapy regimens. AML patients of the M3 subtype displayed an
      induction of the CYP1B1 promoter methylation levels more frequently (57.1%) than
      patients affected by the other subtypes (M1: 33.3%; M2: 12.5%; M4: 16.7%; M5: 0%
      and M6: 0%). In addition, a higher frequency of male patients (4/13) exhibited
      modulation of the CYP1B1 promoter methylation status compared with female
      patients (3/17). Furthermore, of five AML patients with a poor prognosis, two
      exhibited changes leading to CYP1B1 hypomethylation and two leading to CYP1B1
      hypermethylation. By contrast, three other patients exhibited hypermethylation
      changes along with remission. This may be explained by the different chemotherapy
      regimens used to treat these patients or by other unknown factors. The present
      study revealed that CYP1B1 promoter methylation was induced during chemotherapy,
      whereas the APC2 promoter remained hemimethylated. Furthermore, the changes in
      CYP1B1 methylation were dependent on the AML subtypes and the gender of the
      patients.

PMID- 27882115
TI  - Retrospective analysis of seven breast tuberculosis cases.
AB  - The present study aimed to evaluate the demographic data, diagnostic methods,
      therapeutic regimens and duration of therapy in 7 breast tuberculosis (BTB)
      cases. The data of BTB cases treated between January 2006 and December 2013 were
      retrospectively evaluated, with a total of 648 tuberculosis (TB) cases recorded
      during the 8-year period. Among these cases, 296 patients (50%) suffered from
      pulmonary TB, 278 (43%) from non-pulmonary TB and 45 (7%) from PTB plus NPTB. In
      total, 7 BTB were diagnosed, which constituted 1.08% (7/648) of all TB cases and
      2.51% (7/278) of all NPTB cases. The mean age of patients was 34+/-9.46 years,
      with no pregnant or lactating women. Bilateral breast involvement was detected in
      only 1 case, while all cases had a BCG scar, and obtained a mean tuberculin skin
      test (TST) result of 14.28+/-6.79 mm (range, 7-26 mm). The symptoms included
      presence of a mass, tenderness, pain, swelling and fluctuation in the breast,
      with or without discharging sinuses. In 1 case, history of contact with TB was
      found. All patients were newly-diagnosed BTB cases, with no other organ
      involvement. Upon histopathological examination of breast tissue, granulomatous
      inflammation with typical caseous necrosis was observed in 1 case, non-caseous
      necrosis inflammation was detected in 2 cases, granulomatous inflammation was
      observed in 3 cases, and mastitis and fat necrosis inflammation was observed in 1
      case. Acid-fast bacilli (AFB) staining was positive in only 2 cases, and all
      patient were treated with anti-TB drugs with a successful outcome and no
      recurrence. In conclusion, BTB is a rare form of TB and the present retrospective
      study reported 7 cases of BTB along with the results of histopathological
      examination, microbiological examination and treatment. TB must be considered
      when there is presence of breast masses presenting with tenderness, pain,
      swelling and fluctuation, with or without discharging sinuses.

PMID- 27882116
TI  - In vitro and in vivo assessment of high-dose vitamin C against murine tumors.
AB  - Vitamin C is widely used in clinical settings and is well known for its safety.
      Previous studies have shown the efficacy of intravenous vitamin C; however,
      intratumoral delivery of vitamin C has yet to be attempted. In the present study,
      the biological effects of high-dose vitamin C on tumor cells were investigated in
      vitro by using the MTT assay and flow cytometry. When administered in vitro, high
      dose vitamin C inhibited the proliferation of murine colon and breast cancer
      cells, and induced tumor cell apoptosis. Cytotoxicity of vitamin C was partially
      reversed by N-acetyl-cysteine at a relatively low dosage. In addition,
      synergistic anti-tumor effects of vitamin C and cisplatin were observed. In vivo,
      intratumoral delivery of vitamin C delayed tumor growth in murine solid tumor
      models. Considering its low toxicity and availability, the present study
      indicates that vitamin C may be a novel therapeutic method for patients with
      advanced tumors.

PMID- 27882117
TI  - Glycitin regulates osteoblasts through TGF-beta or AKT signaling pathways in bone
      marrow stem cells.
AB  - The aim of the present study was to examine the effect of glycitin on the
      regulation of osteoblasts from bone marrow stem cells (BMSCs) through
      transforming growth factor (TGF)-beta or protein kinase B (AKT) signaling
      pathways. BMSCs were extracted from New Zealand white rabbits and used to analyze
      the effect of glycitin on BMSCs. BMSCs were cleared using xylene and observed via
      light microscopy. BMSCs were subsequently induced with glycitin (0.01, 0.5, 1, 5
      and 10 uM) for 7 days, and stained with Oil Red O. The mechanism of action of
      glycitin on BMSCs was investigated, in which contact with collagen type I (Col
      I), alkaline phosphatase (ALP), TGF-beta and AKT was studied. Firstly, BMSCs
      appeared homogeneously mazarine blue, and which showed that BMSCs were successful
      extracted. Administration of glycitin increased cell proliferation and promoted
      osteoblast formation from BMSCs. Furthermore, glycitin activated the gene
      expression of Col I and ALP in BMSCs. Notably, glycitin suppressed protein
      expression of TGF-beta and AKT in BMSCs. These results indicated that glycitin
      may regulate osteoblasts through TGF-beta or AKT signaling pathways in BMSCs.

PMID- 27882118
TI  - Atypical Miyoshi distal myopathy: A case report.
AB  - Five distinct predominant distal myopathies have been identified with discrete
      clinical and genetic patterns. Miyoshi myopathy (MM; early adult-onset, type 2)
      is a subtype of dysferlinopathy. Furthermore, MM is the most common form of
      autosomal recessive distal myopathy. MM is typically characterized by muscular
      weakness, initially affecting the gastrocnemius or soleus muscle from the late
      teens or early adulthood. The present study reports a case of MM that was
      confirmed by pathological and immunohistochemical methods, in addition to a
      review of the relevant literature. A 37-year-old male patient presented with
      muscular weakness in the left foot. This clinical manifestation was not typical
      of MM, and the patient was initially diagnosed with inflammatory myopathy. He was
      treated with dexamethasone at a dose of 10 mg for 5 days followed by gradual
      tapering, following which the symptoms were alleviated; however, the pathology,
      immunohistochemistry and electromyography eventually confirmed the diagnosis of
      MM. The treatment was then terminated and the patient was discharged. The present
      study further supports the underlying heterogeneity in atypical MM-like
      phenotypes. Dysferlin protein deficiency can be identified by pathological
      examination. The pathology of dysferlinopathy is characterized by changes of
      muscular dystrophy. Inflammatory cellular infiltration is a relatively common
      finding in the muscle biopsies from numerous patients with dysferlinopathy.
      Therefore, the detection of dysferlin deficiency or marked reduction on the
      sarcolemma using immunohistochemical staining is important for the diagnosis of
      dysferlinopathy.

PMID- 27882119
TI  - Bactericidal effect of plasma jet with helium flowing through 3% hydrogen
      peroxide against Enterococcus faecalis.
AB  - The aim of the present study was to assess the antimicrobial activity of plasma
      jet with helium (He) flowing through 3% hydrogen peroxide in root canals infected
      with Enterococcus faecalis. A total of 42 single-rooted anterior teeth were
      prepared, sterilized, inoculated with an E. faecalis suspension and incubated for
      7 days. Next, the teeth were randomly divided into six experimental groups
      (including groups treated by plasma jet with or without He for different time
      durations) and one control group treated without plasma. The number of surviving
      bacteria in each canal was determined by counting the colony forming units
      (CFU)/ml on nutrient agar plates. The results indicated that statistically
      significant reduction in CFU/ml (P<0.005) existed for all treatment groups
      relative to the control group. The greatest reductions in CFU/ml were observed
      for Group 3 (7.027 log unit reduction) and Group 2 (6.237 log unit reduction),
      which were treated by plasma jet sterilization with He flowing through 3%
      hydrogen peroxide for 4 min or for 2 min, respectively. In addition, the
      reduction in Group 3 was significantly greater compared with that in Group 2 or
      in the groups treated by plasma jet sterilization without He flowing through 3%
      hydrogen peroxide for 1, 2 or 4 min. In conclusion, plasma jet with or without He
      flowing through 3% hydrogen peroxide can effectively sterilized root canals
      infected with E. faecalis and should be considered as an alternative method for
      root canal disinfection in endodontic treatments.

PMID- 27882120
TI  - Lutetium 177-DOTA-TATE therapy for esthesioneuroblastoma: A case report.
AB  - Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare
      malignant tumor that accounts for 3% of all tumors of the nasal cavity. The
      incidence of ENB is 0.4 cases per million in the general population, and the most
      common symptoms are nasal obstruction and epistaxis. Previous studies have
      indicated the presence of somatostatin receptors in this tumor type. Common
      treatment strategies for ENB include resection and adjuvant radiotherapy and/or
      chemotherapy (combined treatment); however, the rate of recurrence is high.
      Treatment of neuroendocrine tumors using radionuclides bound to somatostatin
      analogues is well established in clinical practice. However, a standard and
      effective therapeutic approach has not been reported for ENB. The current study
      described the case of a 74-year-old female with numerous recurrences of ENB
      following multiple treatments and without possibility of resection. The patient
      was treated with the radiolabeled-somatostatin analogue, 177Lutetium-DOTA
      octreotate (177Lu-DOTA-TATE), which successfully controlled the disease. This
      suggests that 177Lu-DOTA-TATE is a potential treatment for ENB and may represent
      an effective alternative and novel therapeutic strategy for this disease.

PMID- 27882121
TI  - Stress-induced cardiomyopathy following infection of the upper respiratory tract
      in an elderly female patient: A case report.
AB  - Stress-induced cardiomyopathy (SIC), also known as takotsubo cardiomyopathy
      (TTC), is a relatively newly-described condition, which has been increasingly
      reported in the literature. It is characterized by acute onset of symptoms and
      electrocardiogram changes mimicking myocardial infarction, with transient but
      completely reversible left ventricular (LV) dysfunction. SIC commonly occurs
      following physical or emotional stress. The present study discusses the case of a
      68-year-old female patient who had suffered from infection of the upper
      respiratory tract for 10 days before admission to the hospital with symptoms of
      chest stuffiness and dyspnea that persisted for 2 days. Coronary angiography
      showed normal coronary artery function, while LV angiography demonstrated
      systolic apical ballooning. Based on these observed characteristics, the patient
      was diagnosed with SIC and was successfully treated.

PMID- 27882122
TI  - Gan-Dan-Liang-Yi-Tang alleviates p-chlorophenylalanine-induced insomnia through
      modification of the serotonergic and immune system.
AB  - Gan-Dan-Liang-Yi-Tang (GDLYT) is a Traditional Chinese Medicine that has been
      historically used for the treatment of insomnia. However, investigations into its
      pharmacological ingredients and the mechanism underlying its sedative and
      hypnotic effects remain limited. The present study reported the detailed
      mechanisms underlying the sedative and hypnotic effects of GDLYT. Kunming mice
      were administered GDLYT at various sub-hypnotic doses, which underwent sodium
      pentobarbital treatment test, pentetrazole induced convulsant studies and p
      chlorophenylalanine (PCPA) induced insomnia model. Potentiated hypnotic and
      sedative effects in mice was studied, and also the changes in related
      neurotransmitter and immune factors were evaluated. The results suggested that
      GDLYT possessed weak sedative effects on pentetrazole-induced convulsive activity
      in normal mice at a dose of 1.3 mg/kg, with an increase in sleep onset in
      subhypnotic dose of sodium pentobarbital-treated mice. GDLYT was also able to
      alleviate insomnia induced by PCPA in the rodent models, and increased 5
      hydroxytryptamine levels in the prefrontal cortex, hippocampus, hypothalamus and
      corpus striatum of PCPA-treated rats. Furthermore, the hypnotic effects of GDLYT
      were modified, which allowed for PCPA-induced immune system changes, including
      increased interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-2 expression
      levels. The results of the present study indicated that GDLYT induced sedative
      and hypnotic bioactivity by regulating serotonergic activity in the central
      nervous system and immune system.

PMID- 27882123
TI  - Obesity in relation to oral health behaviors: An analysis of the Korea National
      Health and Nutrition Examination Survey 2008-2010.
AB  - Obesity is reported to be associated with an increased incidence and prevalence
      of periodontal disease. The present study aimed to evaluate the relationship
      between oral health behaviors and obesity in South Korean adults. Data from the
      Korea National Health and Nutrition Examination Survey between 2008 and 2010 was
      used to assess this and a total of 15,666 participants were included in the
      analysis performed. Oral behaviors, including the time of day and rate of tooth
      brushing, and usage of secondary oral products, were considered in this analysis.
      Obesity was defined using the following three methods: Body mass index, waist
      circumference and percentage body fat (PBF). Hierarchical multivariable logistic
      regression analyses were performed to determine the association of oral health
      behavior with obesity after adjusting for possible confounding variables. The
      frequency of daily tooth brushing and usage of secondary oral products was lower
      in individuals with obesity, irrespective of the method used to define obesity.
      Conversely, the risk of general obesity, abdominal obesity and high PBF was
      higher in individuals with a lower daily frequency of tooth brushing and usage of
      secondary oral products.

PMID- 27882124
TI  - (5R)-5-hydroxytriptolide (LLDT-8) prevents collagen-induced arthritis through
      OPG/RANK/RANKL signaling in a rat model of rheumatoid arthritis.
AB  - (5R)-5-hydroxytriptolide (LLDT-8) extracts from Tripterygium have anti
      inflammatory, antineoplastic and immunity adjustment functions. The present study
      used a collagen-induced arthritis (CIA) model to evaluate whether LLDT-8 prevents
      collagen-induced arthritis, and investigated the signaling underlying this. Male
      Sprague-Dawley rats were induced to generate CIA, mimicking rheumatoid arthritis
      (RA). The presence of arthritis was determined using RA progression scores. The
      inflammatory cytokines interleukin (IL)-1beta, IL-6 and nuclear factor-kappaB
      were detected using enzyme-linked immunosorbent assay kits. Induced nitric oxide
      synthase (iNOS) and matrix metalloprotease (MMP)-13 protein expression were
      measured using western blot analysis. Lastly, reverse transcription-quantitative
      polymerase chain reaction was used to evaluate osteoprotegerin (OPG) and receptor
      activator of nuclear factor kappaB (RANK) gene expression. LLDT-8 improved RA
      progression scores and reduced the incidence and severity of CIA. Furthermore,
      LLDT-8 administration inhibited collagen-induced inflammation and iNOS protein
      expression in arthritic rats. The current data indicated that MMP-13 production
      was suppressed and OPG/RANKL expression was increased by LLDT-8 treatment in the
      arthritic rat. The present results suggest that LLDT-8 attenuates CIA through
      OPG/RANK/RANK ligand signaling in a rat model of RA.

PMID- 27882125
TI  - Protective effect of higenamine ameliorates collagen-induced arthritis through
      heme oxygenase-1 and PI3K/Akt/Nrf-2 signaling pathways.
AB  - Existing in Ranunculaceae Aconitum and tomato, with the chemical name 1
      phydroxybenzyl-1,2,3,4-tetrahy-droisoquinoline, higenamine is widely distributed
      in China. Higenamine's anti-inflammatory, antioxidant and anti-apoptotic effects
      have been identified in previous studies. The present study attempted to
      determine the protective effect of higenamine against collagen-induced arthritis
      through heme oxygenase-1 (HO-1) and PI3K/Akt/Nrf-2 signaling pathways. A type II
      collagen (CII)-induced arthritis (CIA) model was established and clinical
      arthritis scores were used to appraise the curative effect of higenamine.
      Inflammatory reactions, oxidative damage and caspase-3/9 activation were detected
      using specific ELISA kits. In addition, western blotting was used to evaluate the
      expression of HO-1, Akt and Nrf-2 protein in CII-induced CIA mice. In CII-induced
      CIA mice, the clinical arthritis scores, inflammatory reactions, oxidation damage
      and caspase-3/9 activation were increased and activated. The results demonstrated
      that treatment with higenamine significantly reduced the elevation of clinical
      arthritis scores (P<0.01), and suppressed the promotion of inflammatory
      reactions, oxidation damage and caspase-3/9 activation. Furthermore, higenamine
      significantly increased HO-1 protein expression (P<0.01) and upregulated the
      PI3K/Akt/Nrf-2 signal pathway in CII-induced CIA mice. Collectively, it is
      concluded that higenamine protects against CII-induced CIA through the induction
      of HO-1 and the upregulation of the PI3K/Akt/Nrf-2 signaling pathway. In
      conclusion, higenamine may be a beneficial drug for protecting against CIA.

PMID- 27882126
TI  - Anticancer activities of alkaloids extracted from the Ba lotus seed in human
      nasopharyngeal carcinoma CNE-1 cells.
AB  - To investigate the anticancer activities of alkaloids from the Ba lotus seed
      (BLSA) in human nasopharyngeal carcinoma (NPC) CNE-1 cells, an MTT assay, flow
      cytometry, reverse transcription-polymerase chain reaction and western blotting
      were performed. BLSA was found to significantly reduce CNE-1 cell proliferation
      in a dose-dependent manner at all concentrations compared with the control
      (P<0.05). In addition, flow cytometry analysis identified that BLSA treatment
      significantly increased the sub-G1 content in CNE-1 cells (P<0.05). Following
      BLSA treatment, the mRNA and protein levels of a number of apoptosis-related
      factors, such as caspase family members (caspase-3, -8 and -9), B-cell lymphoma
      (Bcl)-2-associated X protein, Fas and Fas ligand were significantly increased
      compared with the control (P<0.05). This was accompanied by a significant
      decrease in anti-apoptotic Bcl-2 and Bcl-extra large protein expression compared
      with the control (P<0.05). Furthermore, BLSA treatment was determined to modulate
      CNE-1 cell expression of nuclear factor (NF)-kappaB and NF-kappaB inhibitor
      alpha. The results of the present study indicate that BLSA has anticancer
      activity through inducing cellular apoptosis. In addition, these results suggest
      that BLSA can be used as a therapeutic agent in NPC.

PMID- 27882127
TI  - Evaluation of the efficacy of steroid therapy on acute liver failure.
AB  - The effects of corticosteroids in the treatment of patients with acute or
      subacute liver failure (ALF or SALF) are controversial. The aims of the present
      study were to evaluate the efficacy of corticosteroids in improving spontaneous
      survival (SS) rate in patients with ALF and SALF, and to determine the groups
      with the highest rates of response to, and the most effective timing of,
      corticosteroid administration. A retrospective analysis was performed of all
      patients with ALF and SALF who were hospitalized in the Department of Infectious
      Diseases, Southwest Hospital, Chongqing, China from 2000-2012. The most common
      result of this was SS. A total of 238 patients were studied, including 73
      patients with ALF (n=34 steroids, n=39 no steroids) and 165 patients with SALF
      (n=21 steroids, n=144 no steroids). Corticosteroids improved rates of SS in
      patients with liver failure (steroids vs. no steroids, 38.2 vs. 20.2%; P=0.011),
      including patients with ALF (steroids vs. no steroids, 29.4 vs. 5.1%; P=0.013)
      and with SALF (steroids vs. no steroids, 52.4 vs. 24.3%; P=0.013), patients with
      viruses (steroids vs. no steroids, 32.4 vs. 14.1%; P=0.042) and patients without
      viruses (steroids vs. no steroids, 50.0 vs. 24.1%; P=0.043). SS rates were
      extremely low for patients with coma grade 4 or Model for End-stage Liver Disease
      (MELD) scores >=35 (2.2 vs. 11.8%; P=0.180). A significantly improved rate of SS
      associated with steroid use was observed among patients who had alanine
      aminotransferase (ALT) levels >=30 * the upper limit of normal and coma grade <4
      and MELD scores <35 (65.0 vs. 17.4%; P=0.002). SS associated with steroid use was
      significantly higher in patients with an illness duration <=2 weeks compared with
      patients with an illness duration >2 weeks (51.4 vs. 15.0%; P=0.010).
      Corticosteroids improved the prognosis of patients with ALF and SALF. The highest
      rates of response were observed in patients with a lower MELD score and coma
      grade but who had extremely high ALT levels. The most effective treatment time
      was within 2 weeks of the onset of symptoms.

PMID- 27882128
TI  - MicroRNA-145 sensitizes cervical cancer cells to low-dose irradiation by
      downregulating OCT4 expression.
AB  - Poor elucidation of the mechanisms involved in regulating the radiosensitivity of
      cancers prevents the extensive application of low-dose radiotherapy in clinical
      settings. The present study was conducted to investigate the role of microRNA-145
      (miR-145) in the modulation of cervical cancer cell radiosensitivity, as well as
      to identify the underlying target of miR-145 during this process. Cervical cancer
      tera cells were initially exposed to doses of radiation between 1 and 6 Gy before
      the assessments of the cell viability and apoptosis rate. Irradiation at dose of
      1 Gy was screened as optimum dose and used in subsequent experiments. A dual
      luciferase reporter assay was performed to demonstrate that octamer-binding
      transcription factor 4 (OCT4) is a target of miR-145 in cervical cancer.
      Consequently, OCT4 was suggested to be a target of miR-145, as a dual luciferase
      vector that was ligated to a fragment corresponding to the predicted target site
      of miR-145 in OCT4 3'-UTR showed an 83% reduction in fluorescence. Following
      exposure to 1 Gy irradiation, tera cells transfected with miR-145 mimics, which
      showed downregulation of OCT4 and cyclin D1, had lower cell viability and cell
      migration rate and higher apoptosis rate compared to non-transfected cells.
      However, the co-transfection of miR-145 mimics and OCT4 expression vector
      restored OCT4 and cyclin D1 expression levels and made no significant difference
      in terms of cell viability, cell migration rate and apoptosis rate. The present
      results indicate that miR-145 increases the radiosensitivity of cervical cancer
      cells by silencing OCT4, that cyclin D1 is putatively under the positive
      regulation of OCT4 and mediates miR-145 function.

PMID- 27882129
TI  - Whole-genome resequencing of 100 healthy individuals using DNA pooling.
AB  - With the advent of next-generation sequencing technology, the cost of sequencing
      has significantly decreased. However, sequencing costs remain high for large
      scale studies. In the present study, DNA pooling was applied as a cost-effective
      strategy for sequencing. The sequencing results for 100 healthy individuals
      obtained via whole-genome resequencing and using DNA pooling are presented in the
      present study. In order to minimise the likelihood of systematic bias in
      sampling, paired-end libraries with an insert size of 500 bp were prepared for
      all samples and then subjected to whole-genome sequencing using four lanes for
      each library and resulting in at least a 30-fold haploid coverage for each
      sample. The NCBI human genome build37 (hg19) was used as a reference genome for
      the present study and the short reads were aligned to the reference genome
      achieving 99.84% coverage. In addition, the average sequencing depth was 32.76.
      In total, ~3 million single-nucleotide polymorphisms were identified, of which
      99.88% were in the NCBI dbSNP database. Furthermore, ~600,000 small
      insertion/deletions, 500,000 structure variants, 5,000 copy number variations and
      13,000 single nucleotide variants were identified. According to the present
      study, the whole genome has been sequenced for a small sample subjects from
      southern China for the first time. Furthermore, new variation sites were
      identified by comparing with the reference sequence, and new knowledge of the
      human genome variation was added to the human genomic databases. Furthermore, the
      particular distribution regions of variation were illustrated by analyzing
      various sites of variation, such as single-nucleotide polymorphisms.

PMID- 27882130
TI  - The use of expanded polytetrafluoroethylene in depressed deformities of the face.
AB  - Expanded polytetrafluoroethylene (ePTFE) has been extensively used for facial
      soft tissue augmentation procedures, and is regarded as safe and reliable and
      suitable as a permanent implant. This implant is generally used in the lower
      third of the face for lips filling, nasal augmentation, nasolabial folds and chin
      augmentation, and rarely for congenital or acquired depressed deformities of the
      face. The aim of the present study was to assess the effects of ePTFE in
      congenital or acquired depressed deformities of the face. From September, 2008 to
      January, 2014, 26 patients were implanted with the material ePTFE to correct
      depressed deformities of the face. The average age at operation was 23.2 years,
      with a range of 17-45 years. The depressed deformities were lateralized. The
      follow-up period was 6-18 months (average 9 months). The etiologies of the
      depressed deformities included stable hemifacial atrophy (3 cases), craniofacial
      microsomia (13 cases), bony depression after trauma (8 cases), and other unclear
      reasons (2 cases). The operations were performed under local anesthesia. ePTFE
      was inserted in different tissue planes that varied among the different
      subanatomical areas in the face: beneath the superficial temporal fascia in the
      temporal area, and on the surface of the superficial musculoaponeurotic system in
      the zygomatic area, cheek and mandibular area. All of the patients were followed
      up. Most of the patients [25 of 26 patients (96.2%)] were satisfied with the
      results, while 1 patient (3.8%) was not satisfied for incomplete correction of
      the depressed deformity. In conclusion, aside from lipofilling and a free flap
      transfer, the results showed that ePTFE was an alternative treatment for facial
      depressed deformity.

PMID- 27882131
TI  - Role of peptidylarginine deiminase type 4 in gastric cancer.
AB  - Peptidylarginine deiminase type 4 (PADI4) post-translationally converts
      peptidylarginine to citrulline, appearing to be overexpressed in numerous
      carcinomas. The current study aimed to investigate the expression of PADI4 in
      gastric cancer tissues and its effect on the biological activities of SGC-7901
      and AGS tumor cell lines. The expression of PADI4 was determined in gastric
      cancer and normal gastric mucosa tissues using western blot analysis and reverse
      transcription-quantitative polymerase chain reaction. Gastric cancer cell lines
      were divided into the following groups: Mock group (subjected to transfection
      reagent); negative group [subjected to small interfering RNA (siRNA)
      transfection]; PADI4 siRNA group (subjected to PADI4 siRNA transfection); 5
      fluorouracil (5-Fu) group (subjected to 5-Fu); and 5-Fu + siRNA transfection
      group (subjected to 5-Fu and PADI4 siRNA transfection). The effects of silencing
      PADI4 with the above measures on the proliferation and invasion of SGC-7901 and
      AGS cells were determined by MTT and Transwell chamber assays. In addition,
      propidium iodide staining was performed to detect the effects of PADI4 on the
      cell cycle. A significant increase in the expression of PADI4 mRNA in gastric
      cancer tissue compared with normal mucosa tissue was identified (P<0.05). The
      proliferation and invasion of SGC-7901 and AGS cells were significantly decreased
      in the PADI4 siRNA group. Furthermore, flow cytometry DNA analysis revealed that
      silencing PADI4 resulted in significant S phase arrest and marked decrease of
      cells in the G2/M phase. PADI4 siRNA coupled with 5-Fu significantly enhanced its
      inhibitory effect on the proliferation of gastric cancer cells. In conclusion,
      PADI4 demonstrated high expression in gastric cancer and served an important role
      in the biological activities of gastric cancer cells involving cell
      proliferation, invasion and cell cycle. As a result, PADI4 may be a valid cancer
      susceptibility gene and potential target for cancer therapy.

PMID- 27882132
TI  - Silencing of Wnt5a prevents interleukin-1beta-induced collagen type II
      degradation in rat chondrocytes.
AB  - Osteoarthritis (OA) is a joint disease, and few treatments to date have been able
      to delay OA progression. The degradation of collagen type II (COL2) in the
      cartilage matrix is an important initiating factor for OA progression; the
      upregulation of Wnt5a protein activates COL2 degradation. In the present study,
      small interfering RNA of Wnt-5a was delivered by a lentiviral vector (LV-Wnt5a
      RNAi) to silence Wnt-5a mRNA and prevent COL2 degradation. To determine the
      function of LV-Wnt5a-RNAi, the OA chondrocyte model (OA-like chondrocytes) were
      constructed using interleukin (IL)-1beta. Detected using reverse transcription
      quantitative polymerase chain reaction (RT-qPCR), Wnt-5a mRNA in the OA-like
      chondrocytes were upregulated in a time-dependent manner, indicating that OA-like
      chondrocytes were successfully constructed. The bioactivity of OA-like
      chondrocytes was determined using Live-Dead staining, and the result illustrated
      that the OA-like chondrocytes stimulated with IL-1beta for 6 h remained viable,
      and these were used in Wnt5a silencing. The OA-like chondrocytes were divided
      into three groups: Group I, cultivated with common medium; group II, cultivated
      with common medium supplemented with empty lentiviral vector; group III,
      cultivated with common medium supplemented with LV-Wnt5a-RNAi. The efficiency of
      LV-Wnt5a-RNAi transfection was determined using fluorescence microscopy, the
      result of which indicated that LV-Wnt5a-RNAi could efficiently be transfected
      into the OA-like chondrocytes. The LV-Wnt5a-RNAi efficiency for the Wnt5a mRNA
      silencing was determined using RT-qPCR. The result illustrated that the mRNA of
      Wnt5a in group III was significantly lower in group I compared with that in group
      II (P<0.05), indicating that the LV-Wnt5a-RNAi could successfully silence Wnt5a
      mRNA. To further verify whether the silencing of Wnt5a mRNA could prevent COL2
      degradation, western blotting and immunohistochemical analyses were performed.
      The results demonstrated that COL2 in group III was significantly higher compared
      with that in groups I and II (P<0.05), which illustrated that the silencing of
      Wnt5a mRNA could prevent COL2 degradation. In conclusion, LV-Wnt5a-RNAi was
      formed successfully and could efficiently silence Wnt5a mRNA expressed by OA-like
      chondrocytes. In addition, the silencing of Wnt5a mRNA could prevent the
      degradation of COL2 in OA-like chondrocytes, confirming that LV-Wnt5a-RNAi may be
      used as a novel tool for OA treatment.

PMID- 27882134
TI  - Expression of neutrophil gelatinase-associated lipocalin in low osmolar contrast
      induced nephropathy in rats and the effect of N-acetylcysteine.
AB  - Serum creatinine (Scr), which is a conventional indicator of contrast-induced
      nephropathy (CIN), is unable to reflect the damage of kidney promptly. The
      present study aimed to investigate the value of neutrophil gelatinase-associated
      lipocalin (NGAL) in kidney and serum of CIN rats to observe whether NGAL can be
      used as a superior indicator of CIN. Furthermore, N-acetylcysteine (NAC) was used
      to assess its effect on CIN. A total of 120 adult male Sprague Dawley rats were
      randomly divided into four groups (n=30/group): CIN rats (CIN), normal rats
      treated with NAC (NAC), CIN rats treated with NAC (NAC+CIN) and the control group
      (CON). Serum Scr and NGAL values were measured at 2, 12, 24, 48 and 72 h
      following the procedure. Immunohistochemistry and western blot analysis were used
      to detect NGAL within the kidney tissue. Hematoxylin and eosin staining were used
      to access the renal injury score. Oxidative stress within the kidney was analyzed
      via malondialdehyde (MDA) and superoxide dismutase (SOD). The level of NGAL in
      the serum and tissue of the CIN group increased significantly 2 h after the
      procedure (P<0.05). However, the Scr value did not exhibit a significantly change
      until 48 h later. Based on the renal injury scores, NAC reduced the kidney damage
      caused by the contrast. NAC treatment was associated with a decrease in SOD
      levels and an increase in MDA. These findings suggested that NGAL was a superior
      indicator of CIN than Scr, as NGAL was able to detect kidney damage much earlier.
      Furthermore, NAC treatment inhibited oxidative stress, thus protecting against
      CIN.

PMID- 27882133
TI  - Effects of forced swimming stress on thyroid function, pituitary thyroid
      stimulating hormone and hypothalamus thyrotropin releasing hormone expression in
      adrenalectomy Wistar rats.
AB  - In order to study the impact that is imposed on the hypothalamic-pituitary
      thyroid (HPT) axis of adrenalectomy male Wistar rats by stress caused by
      swimming, the blood level of triiodothyronine (T3), thyroxine (T4) and thyroid
      stimulating hormone (TSH), the expression of TSHbeta mRNA at the pituitary and
      thyrotropin releasing hormone (TRH) expression at the paraventricular nucleus
      (PVN) were measured. A total of 50 male Wistar rats of 6-8 weeks of age and with
      an average weight of 190-210 grams were randomly divided into the following two
      groups: The surgical (without adrenal glands) and non-surgical (adrenalectomy)
      group. These two groups were then divided into the following five groups,
      according to the time delay of sacrifice following forced swim (10 min, 2 h, 12 h
      and 24 h) and control (not subjected to swimming) groups. A bilateral
      adrenalectomy animal model was established. Serum TSH in the blood was
      measurement by chemiluminescent immunoassay, and cerebrum tissue were excised for
      the measurement of TRH expression using an immunohistochemistry assay. In
      addition, pituitaries were excised for the extraction of total RNA. Finally,
      reverse transcription-quantitative polymerase chain reaction was performed for
      quantitation of TSHbeta. Following swimming, the serum T3, T4 and TSH, the
      TSHbeta mRNA expression levels in the pituitary and the TRH expression in the PVN
      of the surgical group were gradually increased. In the non-surgical group, no
      significant differences were observed in the serum T3, T4 and TSH levels compared
      with the control group. The TSHbeta mRNA expression at the pituitary showed a
      similar result. Furthermore, the TRH expression at PVN was gradually increased
      and stress from swimming could increase the blood T4, T3 and TSH levels, TSHbeta
      mRNA expression at the pituitary and TRH expression at the PVN in adrenalectomy
      Wistar rats. Moreover, the index in the surgical group changed significantly
      compared with the non-surgical group. In conclusion, the results suggest that
      there is a positive correlation between stress from forced swimming and the
      variation of the HPT axis.

PMID- 27882135
TI  - Protective effect of eNOS overexpression against ischemia/reperfusion injury in
      small-for-size liver transplantation.
AB  - Ischemia/reperfusion (I/R) injury can occur during small-for-size liver
      transplantation, resulting in delayed graft function and decreased long-term
      graft survival. The aim of the present study was to evaluate the effects of
      genetic overexpression of endothelial nitric oxide synthase (eNOS) in protecting
      hepatocytes against I/R injury in a rat model of small-for-size liver
      transplantation. L02 liver cells were transfected with the eNOS gene using an
      adenovirus (Ad-eNOS). eNOS expression was detected using quantitative polymerase
      chain reaction and western blot analysis. To evaluate the effect of eNOS
      overexpression, L02 cells were placed in a hypoxic environment for 12 h and
      immediately transferred to an oxygen-enriched atmosphere. For in vivo testing,
      rats pretreated with Ad-eNOS or control underwent small-for-size liver
      transplantation. At 6 h after reperfusion, the bile quantity, serum transaminase
      and nitric oxide (NO) levels, and histological outcomes were evaluated. Cell
      apoptosis was assessed by flow cytometry or TUNEL assay. In vitro, Ad-eNOS
      prevented apoptosis in L02 cells with an increase in the level of NO in culture
      supernatant. In vivo, Ad-eNOS pre-treatment significantly increased bile
      production, improved abnormal transaminase levels, diminished apoptosis among
      liver cells, and decreased hepatocellular damage at 6 h after I/R injury. The
      eNOS-mediated renal protective effects might be associated with the
      downregulation of tumor necrosis factor-alpha and a reduction in macrophage
      activation in the early stage of reperfusion in small-for-size liver allografts.
      eNOS-derived NO production significantly attenuates hepatic I/R injury. Thus,
      eNOS overexpression constitutes a promising therapeutic approach to prevent liver
      I/R injury following small-for-size liver transplantation.

PMID- 27882137
TI  - Von Willebrand factor and coagulation factor VIII in Moyamoya disease associated
      with Graves' disease: A case report.
AB  - The present study reported the case of a Chinese boy who was diagnosed with
      Moyamoya disease (MMD) associated with Graves' disease (GD). An overactivation of
      von Willebrand factor (vWF) and coagulation factor VIII (FVIII) was identified in
      the plasma of the patient. Thiamazole and metoprolol treatment was thus
      administrated. After 2 months of treatment, the patient's thyroid function
      returned to normal and the neurological symptoms improved gradually. At the same
      time, the activities of vWF and FVIII were depressed. During the 20-month follow
      up, information regarding the neurological symptoms, cerebrovascular imaging,
      thyroid function, thyroid autoantibodies and coagulation parameters was
      collected. High levels of thyroid autoantibodies persisted throughout the follow
      up period, while other coagulation parameters remained in the normal range. In
      conclusion, considering the vital role of vWF and FVIII in vascular diseases, it
      is hypothesized that these two factors may serve an important role in the
      occurrence of GD associated with MMD.

PMID- 27882136
TI  - Accuracy of contrast-enhanced ultrasound compared with conventional ultrasound in
      acute pancreatitis: Diagnosis and complication monitoring.
AB  - Contrast-enhanced ultrasound (CEUS) has been used for diagnosing acute
      pancreatitis (AP), particularly severe acute pancreatitis (SAP). However, the
      diagnostic difference between CEUS and conventional ultrasonography (CUS) for AP
      and SAP has not been reported. The aim of the present study was to investigate
      the diagnostic accuracy of CUS and CEUS for AP. A total of 196 patients
      clinically diagnosed with AP were selected. All patients underwent CUS, CEUS and
      contrast-enhanced computed tomography (CECT) within 72 h. CECT was considered the
      gold standard. Pancreatic size, peripancreatic fluid collection (PPFC) and
      splenic vessel complications were the variables observed by CUS and CEUS. The
      differences in the variables among the three methods were analyzed using the chi2
      test and statistical analysis software. Significant differences in pancreatic
      size, PPFC and splenic vessel complications in AP were observed between CEUS and
      CUS (P<0.05). chi2 test results indicated that CEUS significantly differed from
      CUS in terms of having a higher diagnostic accuracy for AP and SAP (P<0.05). The
      results indicate that CEUS is a reliable method for the diagnosis and monitoring
      of AP and SAP, and may be substituted for CECT.

PMID- 27882138
TI  - Impact of ethyl pyruvate on Adriamycin-induced cardiomyopathy in rats.
AB  - Ethyl pyruvate (EP), a derivative of pyruvic acid, is known to have protective
      effects against ischemic cardiomyopathy and other disorders. However, little is
      known about its role in Adriamycin (ADR)-induced cardiomyopathy. The present
      study was designed to investigate the impact of EP on ADR-induced cardiomyopathy
      in an animal model. Sixty male Sprague-Dawley (SD) rats were divided into four
      groups: Normal control, EP, ADR and ADR + EP groups (n=15/group). Rats in the ADR
      and ADR + EP groups were treated with ADR (2.5 mg/kg/week intraperitoneally) for
      6 weeks. From the eighth week, rats in the EP and ADR + EP groups received EP via
      gastric lavage at a dose of 50 mg/kg/day for 30 days. After completing the EP
      treatment, cardiac function was assessed by echocardiography and then rats were
      sacrificed. Hearts were harvested for subsequent analysis. Compared with rats in
      the normal control and EP groups (without ADR treatment), rats in the ADR and ADR
      + EP groups showed significant impairments in terms of cardiac function,
      apoptosis, severe oxidative stress and fibrosis in the heart. However, these
      impairments were alleviated by EP treatment in the ADR + EP group. Upon EP
      treatment, cardiac function was significantly improved. The levels of oxidative
      stress, fibrosis and apoptosis in the myocardial tissues were also significantly
      reduced. These findings indicated that EP treatment attenuated, at least
      partially, ADR-induced cardiomyopathy in rats.

PMID- 27882139
TI  - The association between the levels of CRP, IL-10, PLA2, Fbg and prognosis in
      traumatic fracture of lower limb.
AB  - The aim of the present study was to examine changes of sera levels of C-reactive
      protein (CRP), interleukin-10 (IL-10), phospholipase A2 (PLA2) and fibrinogen
      beta polypeptide chain gene (Fbg) in patients with traumatic fracture of lower
      limb, and to evaluate their association with prognosis. The changes in sera
      levels of CRP, IL-10, PLA2 and Fbg were observed at the time of injury, 24 h, and
      5 and 7 days after surgery in 90 patients with traumatic fracture of lower limb.
      In addition, 50 cases, who presented for health examination, were included as the
      normal controls. The expression of sera levels of CRP, IL-10, PLA2 and Fbg in
      patients with traumatic fracture of lower limb, was markedly higher than that in
      the normal controls prior to surgery (P<0.05). The concentration of CRP
      significantly increased within 24 h after emergency, but decreased gradually as
      the wound healed, compared to the controls. Pre- and postoperative IL-10 levels
      increased within 24 h and then decreased gradually. The level of PLA2 in patients
      before and after surgery was increased, and then decreased gradually. The level
      of Fbg in patients with trauma was increased after 24 h and then decreased, and
      increased gradually. The correlation of serum CRP and IL-10 levels (r=0.634,
      P<0.05), and that of PLA2 and IL-10 levels (r=0.617, P<0.05) were positive. In
      conclusion, the expression of CRP, IL-10, PLA2 and Fbg levels in traumatic
      fracture of lower limb markedly increased and was closely associated with
      prognosis. CRP, IL-10, PLA2 and Fbg levels may therefore serve as useful indexes
      in determining the progression and prognosis of patients with traumatic fracture
      of lower limb.

PMID- 27882140
TI  - Hydroxyethyl starch resuscitation downregulate pro-inflammatory cytokines in the
      early phase of severe acute pancreatitis: A retrospective study.
AB  - In the present study, we investigated the effects of hydroxyethyl starch (HES)
      130/0.4 on serum pro-inflammatory variables, immunologic variables, fluid balance
      (FB)-negative(-) rate and renal function in severe acute pancreatitis (SAP)
      patients. From October, 2007 to November, 2008, a total of 120 SAP patients were
      enrolled in this retrospective study. Fifty-nine patients in the HES group
      received 6% HES 130/0.4 combined with crystalloid solution for fluid
      resuscitation (HES group). In the control group, 61 patients received only
      crystalloid solution after admission. Interleukin (IL)-1, IL-6, IL-8 and tumor
      necrosis factor (TNF)-alpha levels in serum were measured on days 1, 2, 4 and 8.
      The peripheral blood CD4+CD8+ T lymphocyte rates, serum BUN and Cr values were
      also measured on days 1, 4 and 8. Patients with FB(-) rates were recorded from
      day 1 to 8. Interaction term analysis (hospital stay and fluid resuscitation
      methods) based on mixed-effects regression model revealed significantly lower
      levels of IL-1 and TNF-alpha in the HES group compared with the control group.
      The difference in curve's risk ratio was not significant for IL-6, CD4+CD8+ T
      lymphocyte rate, BUN and Cr values (P>0.05). In the HES group, we detected a
      significantly higher rate of patients with FB(-) from day 4 to 8 (P<0.05). Thus,
      HES 130/0.4 resuscitation could decrease the IL-1 and IL-8 levels, shorten the
      duration of positive FB, and preserve the patient's immune status as well as
      renal function during the early phase of SAP.

PMID- 27882142
TI  - Multicenter study on the prognosis associated with respiratory support for
      children with acute hypoxic respiratory failure.
AB  - The objective of the present study was to explore the factors influencing the
      outcomes related to respiratory support of children with acute hypoxic
      respiratory failure (AHRF) in 30 hospitals. This was a non-controlled prospective
      and collaborative multicenter clinical study conducted from June, 2010 to May,
      2011 (each hospital for 12 consecutive months). Children aged from 29 days to 6
      years and who met the diagnostic standards of AHRF were enrolled as subjects for
      the study. After patients were enrolled, general parameters including disease
      diagnosis, treatment and prognosis were recorded. Then we analyzed the
      differences in prognosis and respiratory therapy of patients with AHRF. During
      the study period, 13,906 cases of AHRF were admitted among the 30 hospitals,
      accounting for 75.3% of the total number of patients with AHRF. The proportion in
      different hospitals ranged from 16 to 98%. A total of 492 children with hypoxic
      respiratory failure were admitted among the 30 hospitals. The prevalence rate was
      3.54%, and the incidence of AHRF in each hospital was 4.54%. Tidal volume and
      respiratory support treatment were compared with the results from a 2006 study,
      and the differences were statistically significant in positive end-expiratory
      pressure (5 vs. 4, P=0.018), fraction of inspire O2 (0.5 vs. 0.4, P<0.001),
      pressure of artery O2 (70 vs. 60 mmHg, P<0.001) and peak inspiratory pressure (20
      vs. 24 cm H2Omicron, P<0.001). In conclusion, academic background and the level
      of regional economic development are factors which influence the prognosis of
      children with AHRF. On the basis of unapparent differences between academic
      background and the level of regional economic development, there is a substantial
      difference in the prognosis from different forms of respiratory support
      management for AHRF. Therefore, it is essential to develop respiratory support
      and the level of critical management of pediatric intensive care units.

PMID- 27882141
TI  - Clinical study on local application of low-dose insulin for promoting wound
      healing after operation for deep burns.
AB  - Transplanted free skin flaps are often needed to treat deep burns; their
      survival, however, is less than optimal. This study examined whether local low
      dose insulin injections can promote flap survival and wound healing after
      surgery. A total of 165 patients who underwent free skin flap transplantation for
      simple deep burns were enrolled in the study and divided into 5 groups of 33
      patients each: Blank control group (no local subcutaneous drug injections),
      saline control group (saline injections), low-dose insulin group (0.5 units
      regular insulin injections), medium-dose group (1.0 units regular insulin
      injections) and high-dose group (2.0 units regular insulin injections). Wound
      healing and flap survival conditions were assessed and compared among groups. The
      best wound healing rate found was that of the low-dose insulin injection group
      where all the parameters measured improved significantly: The healing time was
      shorter; the blood flow volume, the flap survival, the number of fibroblasts and
      new vessels increased; the re-epithelialization occurred faster; the infiltration
      of inflammatory cells was reduced; the expression levels of heat shock protein
      90, vascular endothelial growth factor, transforming growth factor-beta and
      interleukin-1 were higher; and the plasma glucose levels only fluctuated
      slightly. The results clearly demonstrate that a local low-dose insulin regime
      after flap transplantation can accelerate the healing time and improve the
      surgical outcome without exerting detrimental secondary effects on the glucose
      plasma level of deep burn patients.

PMID- 27882143
TI  - Expression of connexin 43, ion channels and Ca2+-handling proteins in rat
      pulmonary vein cardiomyocytes.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to
      be triggered by ectopic beats, originating primarily in the myocardial sleeves
      surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac
      arrhythmias remain unclear. To investigate this, frozen sections of heart and
      lung tissue from adult rats without arrhythmia were obtained in different planes,
      stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43),
      caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4
      (HCN4), Nav1.5, Kir2.1, and the calcium handling proteins
      sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (SERCA2a) and ryanodine
      receptor 2 (RyR2). Transverse sections offered the best view of the majority of
      the PVs in the tissue samples. Cx43 was observed to be expressed throughout the
      atria, excluding the sinoatrial and atrioventricular nodes, and in the myocardial
      sleeves of the PVs. In contrast, HCN4 was only expressed in the sinoatrial and
      atrioventricular nodes. The immunodensity of Cav3, Nav1.5, Kir2.1, SERCA2a and
      RyR2 in the PVs imaged was similar to that in atria. The results suggest that in
      the absence of arrhythmia, the investigated molecular properties of the ion
      channels of rat PV cardiomyocytes resemble those of the working myocardium. This
      indicates that ectopic beats originating in the myocardial sleeves of the PVs
      occur only under pathological conditions.

PMID- 27882144
TI  - Effect of cyclosporin A intervention on the immunological mechanisms of coronary
      heart disease and restenosis.
AB  - The present study aimed to investigate the effect of cyclosporin A (CSA)
      intervention on the immunological mechanisms underlying coronary heart disease
      (CHD) and restenosis (RS) in rabbits. A total of 48 rabbits were randomly divided
      into normal control (N), N + CSA, CHD model, CHD + CSA, RS model and RS + CSA
      groups. Rabbits in the respective groups received different treatments prior to
      sacrifice at the end of week 12. Iliac arteries were harvested from the rabbits
      for morphological analysis and to determine the mRNA and protein expression
      levels of cluster of differentiation (CD) 40/CD40 ligand (CD40L), CD134/CD134
      ligand (CD134L) and inflammatory factors, including matrix metalloproteinase
      (MMP)-1, MMP-9, vascular cell adhesion protein (VCAM)-1, interleukin (IL)-6 and
      tumor necrosis factor (TNF)-alpha, by reverse transcription-quantitative
      polymerase chain reaction and immunohistochemical staining. As compared with the
      N group, the mRNA expression levels of MMP-9, VCAM-1 and TNF-alpha were
      significantly increased in the CHD and RS groups (P<0.05), but were significantly
      decreased in the groups with CSA intervention, as compared with those without CSA
      intervention (P<0.05). Conversely, there were no significant differences in the
      expression levels of MMP-1 and IL-6 among the six groups, although a decreasing
      trend of IL-6 expression was observed following intervention with CSA.
      Furthermore, there were significant differences in the mRNA and protein
      expression levels of CD40/CD40L and CD134/CD134L among the N, CHD and RS groups
      (P<0.05), and between the groups with and without CSA intervention. The present
      study demonstrated that CSA intervention exerted beneficial effects on CHD and
      RS, and further studies are required to investigate the mechanisms underlying the
      effects of CSA on CHD.

PMID- 27882145
TI  - microRNA-22 attenuates myocardial ischemia-reperfusion injury via an anti
      inflammatory mechanism in rats.
AB  - Previous studies have reported that microRNA-22 (miR-22) may be implicated in
      ischemia-reperfusion (I/R)-induced myocardial injury. Our previously published
      data also demonstrated that miR-22 may protect against myocardial I/R injury via
      anti-apoptosis in rats by targeting cAMP response element-binding protein binding
      protein (CBP). However, the specific function of miR-22 in myocardial I/R injury
      is far from fully elucidated. The present study was designed to investigate
      another cardioprotective signaling mechanism of miR-22 in myocardial I/R injury.
      A total of 40 adult male Sprague-Dawley rats were randomly divided into four
      equal groups (n=10): Sham, myocardial I/R, myocardial I/R with adenovirus
      expressing scramble miRNA (Ad-Scramble) and myocardial I/R with adenovirus
      expressing miR-22 (Ad-miR-22) groups. Besides the Sham operation group, the
      remaining three groups were artificially afflicted with coronary occlusion for 30
      min and subsequently reperfused for 4 h. A light microscope was used to observe
      structural changes in the myocardium; reverse transcription polymerase chain
      reaction was used to measure the miR-22 mRNA expression level; the myocardial
      infarct size was analyzed by the Evans Blue/triphenyltetrazolium chloride double
      staining; and p38 mitogen-activated protein kinase (MAPK), CBP, c-Jun-activator
      protein (AP)-1 and phospho (p)-c-Jun-AP-1 expression protein levels were detected
      by a western blot. Furthermore, ELISA was used to measure the levels of TNF-alpha
      and IL-6 in the myocardium. The results demonstrated that adenovirus-mediated miR
      22 overexpression markedly reduced p38 MAPK, CBP, c-Jun-AP-1, p-c-Jun-AP-1
      expression levels concomitant with an improvement in myocardial injury, including
      smaller infarct size, reduced release of creatine kinase, lactate dehydrogenase
      and proinflammation mediators (tumor necrosis factor-alpha and interleukin-6).
      These findings suggest that miR-22 has a protective effect on myocardial I/R
      injury. This protection mechanism, at least in part, is due to its anti
      inflammatory function via the suppression of the p38 MAPK/CBP/c-Jun-AP-1
      signaling pathway.

PMID- 27882146
TI  - Pulmonary histoplasmosis in a immunocompetent patient: A case report and
      literature review.
AB  - In the present study, the case of a 54-year-old male patient diagnosed with
      pulmonary histoplasmosis is reported, with the aim to increase the understanding
      of the disease characteristics and thereby facilitate the diagnosis and treatment
      of pulmonary histoplasmosis. Clinical manifestations, diagnosis, treatment and
      clinical outcomes of the present case of pulmonary histoplasmosis were described.
      In addition, 76 histoplasmosis patients with complete clinical data were reviewed
      by searching the literature for relevant studies published during 1990 and 2015.
      The disease was mainly manifested as cough in the present case, while imaging
      examination detected a lump shadow in the right lung, accompanied by exudative
      lesions. Initially, the patient was suspected to have bacterial pneumonia, but
      subsequently the diagnosis of pulmonary histoplasmosis was confirmed by lung
      biopsy. The symptoms were alleviated following itraconazole treatment. The
      patient was physically stable and had no recurrence during the subsequent follow
      up period. In conclusion, pulmonary histoplasmosis is characterized by non
      specific clinical and imaging manifestations, and lung tissue biopsy or
      respiratory pathogen culture are regarded as the diagnostic gold standards.
      Individualized antifungal medication should be administered based upon the
      patients' situation in terms of dosage and duration.

PMID- 27882147
TI  - Molecular profiling of a simple rat model of open tibial fractures with hematoma
      and periosteum disruption.
AB  - Bone fractures are a worldwide public health concern. Therefore, improving
      understanding of the bone healing process at a molecular level, which could lead
      to the discovery of potential therapeutic targets, is important. In the present
      study, a model of open tibial fractures with hematoma disruption, periosteal
      rupture and internal fixation in 6-month-old male Wistar rats was established, in
      order to identify expression patterns of key genes and their protein products
      throughout the bone healing process. A tibial shaft fracture was produced using
      the three-point bending technique, the hematoma was drained through a 4-mm
      incision on the medial aspect of the tibia and the fracture stabilized by
      inserting a needle into the medullary canal. Radiographs confirmed that the
      induced fractures were diaphyseal and this model was highly reproducible (kappa
      inter-rater reliability, 0.82). Rats were sacrificed 5, 14, 21, 28 and 35 days
      post-fracture to obtain samples for histological, immunohistochemical and
      molecular analysis. Expression of interleukin-1beta (Il-1beta), transforming
      growth factor-beta2 (Tgf-beta2), bone morphogenetic protein-6 (Bmp-6), bone
      morphogenetic protein-7 (Bmp-7) and bone gamma-carboxyglutamic acid-containing
      protein (Bglap) genes was determined by reverse transcription quantitative
      polymerase chain reaction and protein expression was evaluated by
      immunohistochemistry, while histological examination allowed characterization of
      the bone repair process. Il-1beta showed a biphasic expression, peaking 5 and 28
      days post-fracture. Expression of Tgf-beta2, Bmp-6 and Bmp-7 was restricted to
      the period 21 days post-fracture. Bglap expression increased gradually, peaking
      21 days post-fracture, although it was expressed in all evaluated stages. Protein
      expression corresponded with the increased expression of their corresponding
      genes. In conclusion, a clear and well-defined expression pattern of the
      evaluated genes and proteins was observed, where their maximal expression
      correlated with their known participation in each stage of the bone healing
      process.

PMID- 27882149
TI  - Combination of endogenous neural stem cell mobilization and lithium chloride
      treatment for hydrocephalus following intraventricular hemorrhage.
AB  - As there are multiple factors causing hydrocephalus subsequent to
      intraventricular hemorrhage (IVH), it is difficult to achieve the best treatment
      effect using a single drug alone. In the present study, the protective effect of
      combination treatment with granulocyte-colony stimulating factor (G-CSF) and
      lithium chloride against hydrocephalus after IVH was investigated. A total of 130
      adult male Sprague-Dawley rats were divided into five groups, including the IVH
      control, G-CSF treatment, lithium chloride treatment, combination treatment and
      sham surgery groups. An IVH rat model was established in order to examine the
      effect of combination treatment on hydrocephalus incidence. A TUNEL assay was
      performed to detect neuronal apoptosis in the five groups. In addition, the
      protein expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X
      protein (Bax) were detected by western blot analysis. The differentiation of
      nerve cells in the brain tissue obtained from the five rat groups was also
      determined with double immunofluorescence staining. The results demonstrated that
      administration of G-CSF or lithium chloride alone was able to only partly relieve
      the incidence of hydrocephalus after IVH. By contrast, combination treatment with
      G-CSF and lithium chloride significantly attenuated the development of
      hydrocephalus following IVH. TUNEL assay showed that neuronal apoptosis was
      significantly reduced by the combination treatment with G-CSF and lithium
      chloride. Furthermore, the expression of Bcl-2 was upregulated, whereas Bax
      expression was downregulated in the combination treatment group. The results also
      detected the highest expression of BrdU/GFAP, BrdU/NeuN and BrdU/PSA-NCAM in the
      combination treatment group. In conclusion, the combination of endogenous neural
      stem cell mobilization (using G-CSF) and lithium chloride treatment resulted in
      highly reduced incidence of hydrocephalus after IVH by inhibiting neuronal
      apoptosis.

PMID- 27882148
TI  - Toll-like receptor 4 gene is associated with recurrent spontaneous miscarriage in
      Uygur and Han women in Xinjiang.
AB  - Toll-like receptor 4 (TLR4), a recently identified vertebrate receptor, serves a
      pivotal role in immune responses. The aim of the present study was to investigate
      the association between the human TLR4 gene and recurrent spontaneous miscarriage
      (RSM). A total of 306 RSM patents and 306 age-matched controls were genotyped for
      four single-nucleotide polymorphisms (SNPs) of the human TLR4 gene (rs1927914,
      rs1927911, rs4986790 and rs4986791). Data were analyzed for Uygur and Han women
      separately using a haplotype-based case-control study. There were significant
      differences between the distributions of rs1927914, rs1927911 and rs4986790 SNPs
      between RSM patients and the controls (P=0.001, P<0.001 and P=0.015,
      respectively) were identified in Uygur women, and significant differences between
      the distributions of the rs1927914 and rs1927911 SNPs between RSM patients and
      the controls (P<0.001 and P<0.001, respectively) were identified in Han women.
      Results of the logistic regression analysis indicated that rs1927914, rs1927911
      and rs4986790 SNPs were significantly higher in the RSM patients compared with
      the control individuals (P=0.012, P=0.024 and P=0.035, respectively) in Uygur
      women. Furthermore, significantly higher frequency was noted for the A-G-G
      haplotype (SNP1-SNP2-SNP3) (P=0.016) in RSM patients compared with the controls
      in Uygur women. The results indicate that rs1927914, rs1927911, rs4986790 and the
      A-G-G haplotype (SNP1-SNP2-SNP3) of the human TLR4 gene may be genetic markers
      for RSM in Uygur women, while rs1927914 and rs1927911 SNPs of the human TLR4 gene
      are most likely associated with RSM in Han women in Xinjiang.

PMID- 27882150
TI  - Effect of stromal cell-derived factor-1 on myocardial apoptosis and cardiac
      function recovery in rats with acute myocardial infarction.
AB  - The aim of the study was to investigate the effect of stromal cell-derived factor
      1 (SDF-1) on myocardial apoptosis and cardiac function recovery in rats with
      acute myocardial infarction (AMI) and the mechanism of the Toll-like receptor
      (TLR)-4/nuclear factor-kappaB (NF-kappaB) signaling pathway. A total of 64
      healthy male F344 rats were randomly divided into the sham operation, model, SDF
      1 intervention and SDF-1 antibody groups, with 16 rats in each group. The method
      of Olivette was used to establish the AMI model by ligation of the left anterior
      descending artery. Day 1 after establishing the animal model, the rats in the SDF
      1 intervention group were injected with 10 ul recombinant SDF-1 (400 ng/ml) in
      five regions including the myocardial infarction area and the four surrounding
      areas. The rats in the model group were injected with 10 ul normal saline
      including the myocardial infarction area and the four surrounding areas, and
      those in the SDF-1 antibody group were injected with 1 ml SDF-1 antibody (2
      ug/ml). Four rats were sacrificed after 1, 3, 7 and 14 days after the
      intervention, and the analysis was carried out. TUNEL in situ labeled apoptotic
      cells were used for cell counting, and immunohistochemical staining was performed
      to measure vascular density. The animal echocardiographic measurement was for the
      left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic
      diameter (LVESd), left ventricular fractional shortening (FS) and ejection
      fraction (EF) values. The results showed that the number of apoptotic cells in
      the SDF-1 treatment group was significantly lower than those in the other groups
      at each time-point. The vessel densities in the 3-14 days were significantly
      greater than those in other groups. At each time-point, the LVEDd and LVESd
      values were smaller compared with the model group, but greater than the sham
      operation group and decreased over time. FS and EF values were higher than those
      in the model group at each time-point, but less than those of the sham operation
      group and increased over time. The expression levels of TLR-4 and NF-kappaB at
      each time-point were significantly higher than those of the remaining groups
      (p<0.05). In conclusion, SDF-1 is capable of decreasing the apoptosis of cardiac
      muscle cells in AMI, promoting angiogenesis and improving cardiac function, which
      may be associated with the activation of the TLR-4/NF-kappaB signaling pathway.

PMID- 27882152
TI  - Clinical and molecular study of a pediatric patient with sodium taurocholate
      cotransporting polypeptide deficiency.
AB  - The human solute carrier family 10 member 1 (SLC10A1) gene encodes sodium
      taurocholate cotransporting polypeptide (NTCP), the principal transporter of
      conjugated bile salts from the plasma into hepatocytes. Although the function of
      NTCP has been studied extensively and a number of SLC10A1 variations have been
      identified in humans, information regarding NTCP deficiency is limited. To date,
      only one patient with NTCP deficiency has been described; however, in the present
      study a pediatric patient who experienced intractable and striking
      hypercholanemia is presented. Analysis of the SLC10A1 gene in the patient
      revealed a homozygous p.Ser267Phe (c.800C>T) variation, which proved to be a
      single-nucleotide polymorphism (SNP) in the allele frequency of 4.7% of healthy
      controls. This variation involved a conserved amino acid residue on the
      orthologous alignment that was predicted to be 'disease-causing' by functional
      analysis using a number of bioinformatic tools. Next generation sequencing was
      performed; however, no other genetic causes were identified that would affect the
      bile acid homeostasis in the patient. Moreover, an adult, with the same genotype
      as the pediatric patient, was identified for the first time as experiencing mild
      hypercholanemia. The molecular and clinical findings in the present study
      suggest, for the first time, that there is an association between p.Ser267Phe SNP
      and hypercholanemia, and this information may be used to clinically identify NTCP
      deficiency worldwide.

PMID- 27882151
TI  - Effects of cytomegalovirus infection on the prognosis of inflammatory bowel
      disease patients.
AB  - The aim of the present study was to investigate the effects of cytomegalovirus
      (CMV) infection on the prognosis of inflammatory bowel disease (IBD). Various
      databases were searched using a combination of keywords associated with CMV
      infection and IBD. Subsequent to the selection of relevant studies in line with
      strict inclusion and exclusion criteria, a meta-analysis was conducted using the
      Stata 12.0 software. A total of 195 studies were initially retrieved, including
      28 studies in Chinese and 167 in English. Following the exclusion of unsuitable
      studies, 7 cohort studies with 374 IBD patients were included in the meta
      analysis. The results of the present study identified significant differences
      between patients with and without CMV infection regarding the disease duration of
      IBD [standardized mean difference, -0.81; 95% confidence interval (CI), -1.19 to 
      0.43; P<0.001], the efficacy of corticosteroid therapy [relative risk (RR), 1.24;
      95% CI, 1.02-1.49; P=0.029], the colectomy rate (RR, 2.13; 95% CI, 1.03-4.40;
      P=0.042) and the incidence of severe IBD (RR, 1.32; 95% CI, 1.04-1.67; P=0.022).
      Considering the IBD onset area, patients with CMV infection may have higher
      susceptibility to pancolitis (RR, 1.31; 95% CI; 1.01-1.72; P=0.045); however, no
      difference in susceptibility to left-sided IBD was observed between patients with
      or without CMV infection (RR, 0.97; 95% CI, 0.72-1.30; P=0.828). In conclusion,
      CMV infection may be associated with the disease duration, efficacy of
      corticosteroid therapy, colectomy rate, severe IBD incidence and disease location
      of IBD; thus, the presence of CMV infection may be considered as an important
      biomarker for determining the prognosis of IBD.

PMID- 27882153
TI  - Petroleum ether extract of Chenopodium album L. prevents cell growth and induces
      apoptosis of human lung cancer cells.
AB  - Chenopodium album L. is a common edible herb distributed in China that has been
      used as a traditional Chinese medicine for antiviral, antifungal, anti
      inflammatory and cancer treatment. However, to the best of our knowledge no
      previous reports have investigated its the function of its phytochemical extracts
      in lung cancer cells. The purpose of the present study was to assess the
      anticancer activities of the phytochemical extracts of C. album L. on human non
      small cell lung cancer A549 cells. The present findings demonstrated that the
      petroleum ether (PE) extract of C. album L. exhibited significant growth
      inhibitory effects on A549 with an IC50 value of 33.31+/-2.79 ug/ml. As
      determined by MTT and colony formation assays, its growth inhibitory effects were
      dose- and time-dependent. Furthermore, PE extract-treated A549 cells exhibited
      dose-dependent cell growth arrest at the G1 phase of the cell cycle and cell
      apoptosis was induced. These results provide useful data on the anticancer
      activities of C. album L. in human lung cancer and demonstrated the novel
      possibilities of this plant in developing lung cancer therapies.

PMID- 27882155
TI  - Clinical value of diagnosing aortico-left ventricular tunnel by echocardiography.
AB  - In order to assess the clinical value of echocardiography in the diagnosis of
      aortico-left ventricular tunnel (ALVT) the echocardiographic data and clinical
      manifestations of six patients with ALVT were analyzed in the present study.
      Based on the results, a comprehensive study was conducted regarding 147 cases
      from related documents. Six patients were confirmed with ALVT by surgery. The
      echocardiographic images of the patients revealed an abnormal communication
      beginning in the ascending aorta above the coronary arteries, bypassing the
      aortic valve, and ending in the left ventricle. The color Doppler flow imaging
      showed a high-speed to- and -fro flow with or without the involvement of the
      aortic valve. According to Hovaguimian type casting, there were two cases of type
      I, two cases of type III, one case of type IV, and one case of type II
      (postoperative recanalization). Of the 153 cases reported, the accuracy rate of
      the ultrasound diagnosis was 79.6%, the misdiagnosis rate was 17.1%, and the
      missed diagnostic rate was 3.3%. In conclusion, echocardiography is the preferred
      method for non-invasive preoperative diagnosis of the ALVT and can accurately
      describe the type and involvement of the cardiac structure.

PMID- 27882154
TI  - Kai-Xin-San, a traditional Chinese medicine formulation, exerts antidepressive
      and neuroprotective effects by promoting pCREB upstream pathways.
AB  - Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for
      the treatment of emotion-related disease. However, the underlying mechanism
      remains largely unknown. The present study aimed to examine whether phospho-cAMP
      response element-binding protein (pCREB) and upstream components, such as
      extracellular signal-regulated kinase (ERK), phospho-ERK (pERK),
      phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase
      kinase 3beta (GSK3beta) and pGSK3beta are associated with the antidepressive
      effect of KXS. In total, 24 male Wistar rats were randomly divided into three
      groups, including control (n=8, no treatment), induced with chronic unpredictable
      mild stress (CMS) (n=8), and CMS rats treated with KXS at dosage of 370 mg/kg/day
      orally. Primary hippocampal neuronal cultures were prepared from Wistar rats for
      cell survival and proliferation assays. In KXS rats, increased protein expression
      levels of pCREB, BDNF and tyrosine receptor kinase B (TrkB) were observed in the
      hippocampus and prefrontal cortex, compared with the CMS model group.
      Furthermore, increased expression levels of ERK, pERK, PI3K, Akt, and GSK3beta
      were also detected in the hippocampus and prefrontal cortex of KXS-treated rats
      compared with CMS model rats and in primary hippocampal neuronal cells treated
      with KXS. These results suggest that pCREB and upstream components, including
      TrkB/ERK/CREB and TrkB/PI3 K/CREB, may contribute to the antidepressive effect
      induced by KXS. Further studies are required to confirm these findings.

PMID- 27882156
TI  - Clinical effects of joint application of beta-sodium aescinate and mannitol in
      treating early swelling after upper limb trauma surgery.
AB  - The aim of the present study was to examine the clinical merits of joint
      application of beta-sodium aescinate and mannitol for the treatment of early
      swelling of upper limb trauma after surgery. We verified whether the expression
      of serum aquaporin 1 (AQP-1) was involved in swelling mechanism. A total of 102
      patients with swelling after upper limb trauma surgery were enrolled into the
      study and divided randomly into 3 groups (n=34 cases per group). Group A was
      treated with beta-sodium aescinate; group B was treated with with mannitol and
      group C was treated with both beta-sodium aescinate and mannitol. The expression
      level of AQP-1, and clinical effects and complications before and after treatment
      were comparedS. The time of swelling subsidence in group C was significantly
      shorter than that of the other two groups and differences were statistically
      significant (P<0.05). The recovery ratio and total efficiency in group C were
      significantly higher than those in other two groups and differences were
      statistically significant (P<0.05). Three and seven days after treatment, the AQP
      1 levels in group A and group C were decreased and AQP-1 level decreased further
      with time. Differences of comparison within groups were statistically significant
      (P<0.05), although the differences of comparison between the groups showed no
      statistical significance (P>0.05). We also compared the AQP-1 level in group B
      before and after treatment, and the differences were not statistically
      significant (P>0.05). When the complication incidence in the 3 groups was
      compared, no statistical significance was detected (P>0.05). We concluded that
      the joint use of beta-sodium aescinate and mannitol in treating early swelling
      after upper limb trauma surgery produced satisfactory outcomes. This might be
      related to reduction of the AQP-1 level.

PMID- 27882157
TI  - Analysis of real-time three dimensional transesophageal echocardiography in the
      assessment of left atrial appendage function in patients with atrial
      fibrillation.
AB  - The aim of the study was to examine changes in left atrial appendage volume (LAA
      V) in patients with non-valvular atrial fibrillation (AF) using real-time three
      dimensional transesophageal echocardiography (RT3D-TEE) and evaluate the
      prediction value on the high risk of thrombosis of LAA. Using RT3D-TEE we
      measured: i) LAA peak empty velocity (LAA-PEV), ii) LAA-V including LAA end
      diastolic volume (LAA-EDV) and end-systolic volume (LAA-ESV). We also calculated
      LAA ejection fraction (LAA-EF). RT3D-TEE was applied in 20 control cases and 74
      patients with non-valvular AF. According to the presence of thrombosis, 74
      patients were divided into the no thrombosis group (NTH group, n=52) and
      thrombosis group (TH group, n=22). Our results showed that there were significant
      differences in LAA-V and LAA-EF values in different groups (P<0.05). LAA-EDV
      moderately correlated with LAA-PEV (r=-0.531, P<0.001) while LAA-ESV demonstrated
      a strong correlation with LAA-PEV (r=-0.741, P<0.001). LAA-EF also showed a
      strong correlation with LAA-PEV (r=0.693, P<0.001). Through receiver operating
      characteristic (ROC) curves, the cut-off values of LAA-EDV and LAA-ESV in
      thrombosis of LAA were 18.45 and 9.69 ml, respectively. RT3D-TEE effectively
      evaluated the LAA-V, LAA-PEV and LAA-EF parameters, and proved to be valuable in
      the process of evaluation of thrombosis of LAA.

PMID- 27882158
TI  - Functional characterization of human umbilical cord-derived mesenchymal stem
      cells for treatment of systolic heart failure.
AB  - Congestive heart failure (HF) is a leading cause of morbidity and mortality
      worldwide. Although advances in medical therapy, mechanical support and heart
      transplantation have been made, almost half of all patients with HF succumb to
      the disease within five years of the initial diagnosis. Therefore, treatment
      methods need to be identified to restore the structure and function of cardiac
      muscle. Three patients with HF caused by ischemic cardiomyopathy received human
      umbilical cord-derived mesenchymal stem cell (HUC-MSC) intravenous infusion were
      included in the present study. Two patients demonstrated a 65.1% increase in left
      ventricular ejection fraction (LVEF) at the end of 3 months, which was maintained
      increasing 47.8% at the end of 12 months post-HUC-MSC intravenous infusion. LVEF
      of patient 1 decreased slowly in the observation period. This LVEF improvement
      was associated with significant improvements in the clinical parameters of the
      New York Heart Association class, and six-minute walk test in the coupled time.
      The third patient showed significant improvement in the six-minute walk test at
      the end of 12 months, while the other parameters did not change obviously. There
      were no severe adverse events during and post-HUC-MSC transplantation. During
      follow-up, no other immunosuppressive drugs were used. In conclusion, HUC-MSC
      therapy is a reasonable salvage treatment in HF. Future large-scale randomized
      clinical trials are likely to be designed to elucidate the efficacy of the HUC
      MSC transplantation therapy on HF.

PMID- 27882159
TI  - National trends for open and endovascular repair of aneurysms in Korea: 2004
      2013.
AB  - The introduction of endovascular aneurysm repair has led to a dramatic decline in
      open aneurysm repair. The aim of this report was to evaluate Korean national
      trends for the treatment of aneurysms. A serial, cross-sectional study of time
      trends of patients who underwent aneurysm repair between 2004 and 2013 was
      conducted. Data from the Health Insurance Review and Assessment Service were used
      to evaluate the trends of aneurysm repair in the Korean population and to analyze
      the trends of open and endovascular aneurysm repair among Medicare beneficiaries.
      A linear-by-linear association was performed to determine alterations in the
      rates at which these aneurysm repair techniques were performed. A total of 32,130
      patients underwent aneurysm repair between 2004 and 2013. The proportion of
      patients who underwent open repair decreased from 94.0% in 2004 to 54.9% in 2013;
      whereas the proportion of patients who underwent endovascular repair increased
      from 6.0% in 2004 to 45.1% in 2013. During the study period, the number of
      patients undergoing endovascular repair of aortic aneurysms significantly
      increased from 82 to 1,396 (relative risk, 16.17; 95% confidence interval: 12.94
      20.21). Endovascular repair of abdominal aortic aneurysms (AAAs)overtook open
      repair between 2010 and 2011. The frequency of open aneurysm repair increased 1.2
      fold, with an overall downward trend. The prevalence of endovascular repair
      markedly increased 15.3-fold. These findings indicated that, in Korea, the
      endovascular repair of AAAs overtook open repair as the most common technique
      between 2010 and 2011.

PMID- 27882160
TI  - Disseminated nocardiosis caused by Nocardia otitidiscaviarum in an
      immunocompetent host: A case report and literature review.
AB  - The aim of the present study was to summarize the clinical characteristics of
      nocardiosis caused by Nocardia otitidiscaviarum in order to improve the knowledge
      of nocardiosis. A case of dissemination nocardiosis caused by N. otitidiscaviarum
      in an immunocompetent host is reported and the associated literature reviewed.
      Informed consent for publication of this case report was provided by the patient.
      The present patient was a young immunocompetent man suffering from disseminated
      nocardiosis induced by infection with N. otitidiscaviarum. Following a poor
      response to beta-lactam antibiotic, a combination of sulfonamide with minocycline
      was administered, which successfully ameliorated the symptoms. Previous studies
      published in English were retrieved from PubMed with 'Nocardia otitidiscaviarum'
      used as the search keyword. A total of 23 articles were retrieved from the PubMed
      database, supporting the assertion that N. otitidiscaviarum is a rare Nocardia
      species. Among these 23 cases, there were 11 cases of lymphocutaneous (48%), 5 of
      pulmonary (22%), 2 of brain (9%) and 1 of pyothorax (4%) infection, and 4 cases
      of disseminated infections (17%). Analysis of the immune state of these patients
      demonstrated that 9 were immunocompetent (39%), 7 of whom had cutaneous
      infections (30%) with a predominant history of trauma (6/7), and 14 were
      immunosuppressed, 9 of whom were treated with prednisolone. Microbiology and
      histopathology were necessary in all cases for definite diagnosis. Among the 13
      cases who underwent drug susceptibility testing, 10 cases were sensitive to
      trimethoprim-sulfamethoxazole (TMP-SMX) and 12 cases were sensitive to
      aminoglycoside. In conclusion, although N. otitidiscaviarum is one of the less
      commonly isolated species of Nocardia, it is capable of inducing localized or
      disseminated infection, even in an immunocompetent host. The majority of cases
      respond well to TMP-SMX and aminoglycoside, but the therapeutic action of
      cephalosporin is weak. Identification of bacteria and drug sensitivity tests for
      Nocardia is critical for guiding clinical treatment.

PMID- 27882161
TI  - Potential diagnostic role of diffusion tensor imaging in early-stage
      osteonecrosis of the femoral head.
AB  - The present study aimed to explore the potential diagnostic role of diffusion
      tensor magnetic resonance imaging (DTI) in the early stage of modified
      corticosteroid-induced osteonecrosis of the femoral head (ONFH). A total of 20
      beagles were randomly classified (1:1) into either an experimental group (LM),
      which were intramuscularly injected with lipopolysaccharide (LPS) and
      methylprednisolone (MPS) on three consecutive days, or control (CON) group, which
      were injected with saline. Magnetic resonance imaging (MRI) and DTI were
      performed at pre-induction and 8 and 12 weeks post-induction. Apparent diffusion
      coefficient (ADC) values in the range of interest in the femoral head were
      quantified using DTI. Proximal femora were examined for ONFH at 8 and 12 weeks.
      The results demonstrated that ONFH developed in four beagles at 8 weeks and in
      six beagles at 12 weeks, whereas no ONFH was detected in the CON group. No
      abnormalities were detected by MRI and DTI, and no mortality occurred. In beagles
      with ONFH in the LM group, the ADC values were 4.7+/-0.2*10-4 and 4.8+/-0.3*10-4
      mm2/sec at 8 and 12 weeks, respectively, which were significantly increased
      compared with the CON group (2.5+/-0.3*10-4 and 2.4+/-0.3*10-4 mm2, respectively)
      and the LM group without ONFH (2.6+/-0.4*10-4 and 2.4+/-0.3*10-4 mm2,
      respectively) (P<0.05). The results of the present study indicated that
      intramuscular injection of LPS and MPS may lead to early-stage ONFH in beagles.
      As such, the detection of locally elevated ADC values in the femoral head may aid
      in the early diagnosis of ONFH.

PMID- 27882162
TI  - Evaluation of the health-related quality of life using the 36-item short form
      health survey in patients with chronic hepatitis C receiving pegylated
      interferon/ribavirin/telaprevir triple treatment.
AB  - The rate of sustained virologic response (SVR) has increased in patients with
      chronic hepatitis C (CHC; genotype 1) since triple treatment with pegylated
      interferon (PEG-IFN), ribavirin (RBV) and telaprevir (TVR) was included in
      Japanese health insurance. However, side effects such as high-grade anemia and
      skin disorders means it is important to investigate the extent to which quality
      of life (QOL) is maintained during treatment. The impact on health-related (HR)
      QOL, as a result of TVR-based triple treatment was investigated long-term (48
      weeks) in 34 patients (18 men, 16 women) following TVR-based triple treatment,
      using the 36-item short form health survey (SF-36). While scores for physical
      health were significantly lower during treatment, an improvement was seen in
      patients who showed complete response to treatment from 12 weeks following
      treatment (P<0.05). HRQOL improved significantly following completion of TVR
      based triple treatment in these complete-responders, with higher scores compared
      with those prior to treatment. Anemia and skin symptoms appeared frequently
      during treatment and scores for physical health dropped. Particular care needs to
      be taken in regards to the management of side effects during TVR treatment.
      Further evaluations using the SF-36 may help in controlling doses to achieve SVR.

PMID- 27882163
TI  - Insulin-induced autoimmune syndrome: A case report.
AB  - Insulin autoimmune syndrome (IAS) is a disease characterized by hyperinsulinemic
      hypoglycemia associated with autoantibodies against endogenous insulin. A 56-year
      old man was admitted to Ningbo First Hospital for the treatment of spontaneous
      hypoglycemia. He was found to have elevated fasting insulin level (>1,000 mIU/l)
      and presence of insulin autoantibodies, and after appropriate workup, was
      diagnosed with IAS. After treating with prednisone for 2 months, his insulin
      level started decreasing. In patients with repeated hypoglycemia, IAS should be
      considered in the differential diagnosis. Prednisone may be effective for the
      treatment of hypoglycemia in patients with IAS.

PMID- 27882164
TI  - Inflammatory bowel disease in Chinese children: A retrospective analysis of 49
      cases.
AB  - To present study reports the clinical characteristics, diagnosis and management
      of pediatric patients with inflammatory bowel disease (IBD) in China. Clinical
      records of 49 pediatric patients with IBD at Fudan University Children's Hospital
      (Shanghai, China) between July 2001 and May 2012 were reviewed. Of 49 patients
      (30 males and 19 females), 8 patients had ulcerative colitis (UC) and 41 patients
      had Crohn's disease (CD). The mean age was 10.4 years in patients with UC and
      10.1 years in patients with CD. The percentages of patients with UC with
      abdominal pain, diarrhea or rectal bleeding were 62.5, 100 and 87.5%,
      respectively, and that of CD patients were 75.6, 61 and 39%, respectively.
      Patients with UC were underweight (37.5%), and had oral ulcers (12.5%) and
      arthritis (12.5%), and patients with CD were underweight (34.1%), and had oral
      ulcers (26.8%), anal fistulas (22%) and arthritis (19.5%). Patients with CD had a
      higher proportion of immunoglobulin G, C-reactive protein and erythrocyte
      sedimentation rate compared with patients with UC. Histologic lesions of patients
      with UC were primarily located in the sigmoid colon (75%), transverse colon (50%)
      or pan-colon (50%), and in patients with CD they were located in the distal ileum
      (51.2%), ileocecum (58.5%) or upper gastrointestinal tract (41.5%). All patients
      underwent colonoscopies and 13 underwent double-balloon enteroscopies. Standard
      treatment for IBD, including corticosteroids, 5-aminosalicylate, and
      immunosuppressants (6-mercaptopurine and azathioprine), were administered to all
      patients. In addition 3 patients were treated with infliximab and 10 patients
      were treated with thalidomide. Comprehensive assessment of clinical, laboratory,
      endoscopic, and pathohistological data will benefit the timely diagnosis of IBD.

PMID- 27882165
TI  - Emodin inhibits migration and invasion of MHCC-97H human hepatocellular carcinoma
      cells.
AB  - Emodin, an anthraquinone derivative from the root and rhizome of Rheum palmatum
      L., was found to have antitumor effects in different types of cancer by
      regulating multi-molecular targets. The aim of the present study was to explore
      the effect of emodin on the migration and invasion of MHCC-97H human
      hepatocellular carcinoma cells and the underlying molecular mechanisms. Firstly,
      it was demonstrated that emodin can inhibit cell proliferation and induce
      apoptosis of cells in a time- and dose-dependent manner, using a MTT assay and
      flow cytometry, respectively. However, when emodin concentration was <50 umol/l,
      it had little effect on the inhibition of proliferation or the induction of
      apoptosis. Then, it was observed that emodin can significantly suppress cell
      migration and invasion with a treatment dose <50 umol/l compared with the control
      (P<0.05), which was not attributed to a decrease in cell number. Further study
      demonstrated that emodin significantly suppressed the expression levels of matrix
      metalloproteinase (MMP)-2 and MMP-9 compared with the control, which may be
      mediated by the activation of the p38 mitogen-activated protein kinases (MAPK)
      signaling pathway and suppression of extracellular signal regulated kinase
      (ERK)/MAPK and phosphatidylinositol 3-kinase/Akt signaling pathways. Therefore,
      the present study, for the first time, used MHCC-97H cells, which have the high
      potential of malignant invasion, to demonstrate that emodin may inhibit cell
      migration and invasion.

PMID- 27882166
TI  - Galanin receptor 2 mediates antifibrogenic effects of galanin on hepatic stellate
      cells.
AB  - Galanin is an endogenous factor involved in the negative regulation of the
      biological effects of leptin in bioenergetic metabolism. Leptin promotes
      fibrogenic effects in hepatic stellate cells (HSCs), however, little is known
      about the effects of galanin on HSCs. In the present study, the biological
      functions of galanin and its receptors (GalRs) in HSCs were investigated using
      cell culture in vitro. It was found that galanin and GalR3 mRNA are expressed in
      quiescent and activated HSCs. GalR2 expression was undetectable in quiescent HSCs
      but was markedly induced in activated HSCs. In the HSC-T6 cell line, which is an
      activated rat HSC cell line, treatment with 100 nmol/l galanin significantly
      inhibited cell proliferation. It also inhibited transforming growth factor (TGF)
      beta1 and alpha-smooth muscle actin (SMA) expression and upregulated peroxisome
      proliferator-activated receptor (PPAR)-gamma expression. Following the knockdown
      of GalR2 by specific small interfering RNA, the activation of GalR3 by galanin
      does not influence these effects of galanin on HSCs. However, activation of GalR2
      alone by galanin following the knockdown of GalR3 inhibits HSC proliferation and
      TGF-beta1 and alpha-SMA expression, in addition to inducing PPAR-gamma
      expression. These data suggest that galanin inhibits HSC activation and
      suppresses the profibrogenic features of these cells, and these effects might be
      mediated by GalR2. Thus, galanin is a potential endogenous factor in the
      inhibition of liver fibrosis.

PMID- 27882167
TI  - Expression and functions of the STAT3-SCLIP pathway in chronic myeloid leukemia
      cells.
AB  - Chronic myeloid leukemia (CML) is a blood cell cancer with increased
      proliferation of granulocytes. Signal transducers and activators of transcription
      3 (STAT3) is an important regulator of CML. To investigate the possible
      downstream factors of STAT3 and gain more insight into CML-related pathways, this
      study focused on the superior cervical ganglia protein 10-like protein (SCLIP, or
      SCG 10-like protein) and analyzed the functions of the STAT3-SCLIP pathway. The
      effects of STAT3 phosphorylation on SCLIP expression were examined by western
      blotting. Specific small interfering RNA (siRNA) was then used to knockdown SCLIP
      in the CML cell line K562 and the expression changes of STAT3 and factors further
      downstream, namely Bcl-2 and cyclin E1, were detected by RT-qPCR. Cell viability
      and apoptosis were also analyzed following the knockdown of SCLIP. Results showed
      a positive association between the phosphorylation of STAT3 and the expression of
      SCLIP. Knockdown of SCLIP inhibited the viability and induced the apoptosis of
      K562 cells. Knockdown of SCLIP did not affect the expression of STAT3 mRNA but
      downregulated the mRNA levels of Bcl-2 and cyclin E1. In conclusion, the results
      indicate that SCLIP is a direct downstream factor of STAT3, regulates Bcl-2 and
      cyclin E1 and mediates the viability and apoptosis of CML cells. Consisting of at
      least these four factors, the STAT3-SCLIP pathway might play critical roles in
      the regulation of CML. These data provided a more profound understanding of CML
      related pathways.

PMID- 27882168
TI  - Monozygotic twins with infantile neuroaxonal dystrophy: A case report and
      literature review.
AB  - Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease with
      early onset. PLA2G6 gene mutations have been identified in the majority
      individuals with INAD. In future, molecular diagnosis of INAD will replace the
      invasive biopsies used previously. In the present report, monozygotic male twins
      with INAD were referred The Children's Hospital (Zhejiang University School of
      Medicine, Zhejiang, China) at fifteen months old for delayed development. The
      older brother was found to have developmental stagnation when he was 6 months
      old. The patient could not stand securely without support, and had poor eye
      tracking and listening ability. Magnetic resonance imaging (MRI) of the patient's
      brain revealed cerebellar atrophy and electromyography identified signs of
      peripheral neuropathy. The younger brother displayed similar clinical features
      and findings. Two different phospholipase A2 group VI (PLA2G6; 22q13.1) gene
      mutations were detected in the twins by DNA sequencing. The results of the
      present study indicate that neurogenetic disease should be considered when child
      patients present with idiopathic developmental stagnation, particularly when
      similar cases have appeared in the same family. In addition, INAD should be
      considered as a possible diagnosis when the patient has developmental delay of
      the central and peripheral nerves. In the future, molecular genetic testing will
      be the primary method of INAD diagnosis, enabling better prevention of this
      genetic disease.

PMID- 27882170
TI  - Acute encephalitis with refractory, repetitive partial seizures: A case report
      and literature review.
AB  - A male 46 year-old patient was admitted to the Emergency Intensive Care Unit of
      Qinghai Provincial People's Hospital (Xining, China) in December 2008 with
      complaints of a headache and fever that had lasted for three days. In addition,
      the patient had experienced two general convulsions accompanied with
      consciousness disorders for 7 h. Although the patient's clinical manifestations,
      laboratory tests and cerebrospinal fluid examinations were consistent with
      numerous features associated with acute encephalitis, the patient's clinical
      course was different to that of acute encephalitis, and the prognosis was poor.
      The clinical course of the patient fully complied with the diagnostic criteria of
      acute encephalitis with refractory, repetitive partial seizures (AERRPS), as
      follows: i) The acute phase of encephalitis lasted >2 weeks; ii) partial seizures
      accompanied with general seizures occurred throughout the acute and convalescent
      course; iii) frequent seizures, a number of which resulted in a sustained state,
      were more prominent in the acute phase; iv) seizures were difficult to control;
      and v) known viral encephalitis and systemic metabolic disorders were excluded
      from the diagnosis. Based on previous reports and the present study, it can be
      concluded that AERRPS does not respond to the majority of anti-epileptic drugs,
      and while high-dose phenobarbital was effective in the current study, it was not
      able to fully control the focal and general seizures. Despite this, phenobarbital
      is required for maintenance in the recovery phase.

PMID- 27882169
TI  - Efficacy of mesenchymal stem cells in treating patients with osteoarthritis of
      the knee: A meta-analysis.
AB  - To assess the clinical efficacy and safety of mesenchymal stem cell (MSC)
      treatment for osteoarthritis of the knee (KOA), a systematic electronic
      literature search was performed on PubMed, EMBASE and Web of Science. Studies
      published in English from the earliest record to December 2014 were searched
      using the following keywords: Cartilage defect, cartilage repair, osteoarthritis,
      KOA, stem cells, MSCs, bone marrow concentrate (BMC), adipose-derived mesenchymal
      stem cells, synovial-derived mesenchymal stem cells and peripheral blood-derived
      mesenchymal stem cells. The effect sizes of selected studies were determined by
      extracting pain scores from the visual analog scale and functional changes from
      International Knee Documentation Committee and Lysholm and Western Ontario and
      McMaster Universities Osteoarthritis Index before and after MSCs or reference
      treatments at 3, 6, 12, and 24 months. The factors were analyzed and the outcomes
      were modified after comparing the MSC group pooled values with the pretreatment
      baseline or between different treatment arms. A systematic search identified 18
      clinical trials on this topic, including 10 single-arm prospective studies, four
      quasi-experimental studies and four randomized controlled trials that used BMCs
      to treat 565 patients with KOA in total. MSC treatment in patients with KOA
      showed continual efficacy for 24 months compared with their pretreatment
      condition. Effectiveness of MSCs was improved at 12 and 24 months post-treatment,
      compared with at 3 and 6 months. No dose-responsive association in the MSCs
      numbers was demonstrated. However, patients with arthroscopic debridement,
      activation agent or lower degrees of Kellgren-Lawrence grade achieved improved
      outcomes. MSC application ameliorated the overall outcomes of patients with KOA,
      including pain relief and functional improvement from basal evaluations,
      particularly at 12 and 24 months after follow-up.

PMID- 27882171
TI  - Role of microRNA-141 in colorectal cancer with lymph node metastasis.
AB  - The present study aimed to investigate the role of microRNA (miR)-141 in the
      pathogenesis of colorectal cancer (CRC). In total, 58 CRC patients were included
      in the present study. The mRNA and protein expression levels of mitogen-activated
      protein kinase 4 (MAP4K4) were detected by reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The
      miRNA-141 expression was measured by RT-qPCR, while serum MAP4K4 content was
      detected by enzyme-linked immunosorbent assay. Natural killer (NK) cells and T
      cells in peripheral blood were detected by flow cytometry. The results indicated
      that the mRNA and protein expression levels of MAP4K4 were significantly elevated
      in the tumor tissues, lymph nodes (P<0.01) and serum (P<0.05) in CRC.
      Furthermore, the expression levels of MAP4K4 in CRC patients with lymph node
      metastasis were higher compared with those in patients without metastasis.
      Bioinformatics analysis revealed that MAP4K4 may be the target gene of miRNA-141.
      The expression levels of miRNA-141 in the tumor tissues, lymph nodes and serum
      were significantly decreased in CRC patients, with a more evident decline in
      cases with lymph node metastasis. In addition, the percentage of NK, CD3+ T and
      CD4+ T cells was significantly decreased, whilst the number of CD8+ T cells was
      significantly increased, in the peripheral blood in CRC. The present results
      showed that miRNA-141 was downregulated in CRC, which increased the expression
      levels of MAP4K4 and altered the anti-tumor response, further increasing the
      proliferation, invasion and metastasis of the tumors. These findings may
      contribute to improving the current understanding of the pathogenesis of CRC, and
      lead to the development of therapies involving miRNA-141.

PMID- 27882172
TI  - Downregulated miR-486-5p acts as a tumor suppressor in esophageal squamous cell
      carcinoma.
AB  - microRNAs (miRNAs/miRs) are crucial regulators of gene expression at the post
      translational level through promoting mRNA degradation or the repression of
      translation of target genes. miRs have been confirmed to serve a dominant role in
      tumor biology. miR-486-5p has been ascertained to be involved in non-small-cell
      lung cancer, breast cancer and hepatocellular carcinoma; however, the expression
      and function of miR-486-5p in esophageal squamous cell carcinoma (ESCC) has yet
      to be elucidated. The present study aimed to analyze the expression levels of miR
      486-5p in ESCC tissues and paired normal adjacent tissues, and determine the
      effects of miR-486-5p on esophageal cancer cells using MTT, wound scratch and
      apoptosis assays. The current results showed that miR-486-5p was significantly
      downregulated in ESCC specimens. Ectopic expression of miR-486-5p by synthetic
      mimics reduced cell proliferation and migration and induced increased cell
      apoptosis. The results indicated miR-486-5p may function as a tumor suppressor in
      ESCC. The present study demonstrated that miR-486-5p was downregulated in ESCC
      and served a anti-oncogene role in ESCC via affecting cellular migration.

PMID- 27882173
TI  - Anti-human fibroblast growth factor-21 monoclonal antibody preparation,
      characterization and analysis of in vitro bioactivity.
AB  - Human fibroblast growth factor 21 (hFGF-21) is involved in numerous metabolic
      processes and elevated hFGF-21 levels are associated with many metabolic
      diseases. However, the role hFGF-21 serves in the metabolic system is not fully
      understood. A humanized anti-hFGF-21 monoclonal antibody (mAb) would provide a
      novel method for further investigations into the role hFGF-21 serves in the
      metabolic system and related diseases, which may reveal therapeutic targets for
      future treatment of these diseases. The present study aimed to prepare an anti
      hFGF-21 mAb, followed by identification of its characteristics and bioactivity in
      vitro. The results of the present study identified that the anti-hFGF-21 mAb
      (clone 2D8) produced had good specificity, had an immunoglobulin isotype of IgG2b
      and a titer of 1:1.024*106. hFGF-21 was screened for epitopes using fluorescence
      activated cell sorting, which revealed a specific 15 amino acid sequence
      (YQSEAHGLPLHLPGN) that the anti-hFGF-21 mAb recognized. In vitro bioactivity of
      anti-hFGF-21 was determined using a glucose uptake assay and by measuring the
      expression of glucose transporter 1 (GLUT1) messenger RNA (mRNA) in 3T3-L1
      adipocytes. This revealed that hFGF-21-dependent glucose uptake and GLUT1 mRNA
      expression were negatively correlated with increasing levels of the anti-hFGF-21
      mAb tested, and that hFGF-21 activity could be overcome by increasing
      concentrations of the mAb, demonstrating that the mAb has hFGF-21-neutralizing
      activity in vitro.

PMID- 27882175
TI  - Tea polyphenols protect against ischemia/reperfusion-induced liver injury in mice
      through anti-oxidative and anti-apoptotic properties.
AB  - Tea polyphenols (TPs), which are derived from tea extracts, are a class of
      chemicals containing polyphenol hydroxyls that have been observed to have strong
      anti-oxidative properties. Previous studies have demonstrated that TP can protect
      against hepatic ischemia/reperfusion (I/R) injury; however, the underlying
      mechanism remains unknown. In the present study, the mechanism underlying TPs
      protective effects against I/R-induced liver damage was investigated, focusing on
      its anti-oxidative and anti-apoptotic bioactivities. C57BL/6 mice were used to
      establish a hepatic I/R-induced injury model, and liver injury was analyzed using
      a biochemical assay. The results from the current study demonstrated that the
      serum expression levels of aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) were significantly increased in mice following hepatic I/R
      injury, while the ratio of hepatic glutathione (GSH)/oxidized GSH (GSSG) was
      reduced, indicating that liver damage had occurred. In mice that were orally
      administered with TP (50 mg/kg) 1 h prior to I/R-induced injury, the extent of
      liver injury was significantly attenuated. It was also observed that I/R injury
      significantly decreased the mRNA and protein expression levels of cytokine
      inducible nitric oxide synthase in liver tissues, and this was also attenuated by
      pretreatment with TP. Furthermore, pretreatment with TP significantly attenuated
      the I/R-induced increase in liver cell apoptosis, and the expression level and
      activity of pro-apoptotic proteins in the liver, indicating that I/R-induced
      liver cell apoptosis is inhibited by TP. In conclusion, the results in the
      present study suggest that TP protects against hepatic I/R-induced injury by
      inhibiting I/R-induced oxidative damage and liver cell apoptosis.

PMID- 27882174
TI  - Reduction of p38 mitogen-activated protein kinase and cyclooxygenase-2 signaling
      by isoflurane inhibits proliferation and apoptosis evasion in human
      papillomavirus-infected laryngeal papillomas.
AB  - Human laryngeal papilloma (LP) is a human papillomavirus-induced hyperplastic
      tumor of the respiratory tract, which is characterized by rapid growth and
      apoptosis resistance. Isoflurane (ISO) inhibits proliferation and elicits
      apoptosis in cancer cells. The results of the present study found that the mRNA
      and protein levels of cyclooxygenase-2 (COX2) were higher in LP tissues than in
      normal laryngeal samples, and prostaglandin E2 (PGE2) production was increased in
      LP cells, as determined by quantitative polymerase chain reaction, western blot
      and radioimmunoassay analyses. Notably, the increase in COX2 and PGE2 levels was
      significantly abrogated in the ISO-treated LP cells. The inhibitory effects of
      ISO on COX2 expression and activity depended on the inactivation of p38 mitogen
      activated protein kinase (MAPK) in LP cells. By inhibiting the COX2 activity of
      LP cells, ISO treatment markedly suppressed cell viability and proliferation, as
      determined using Cell Counting Kit-8, flow cytometry and 5-ethynyl-20
      deoxyuridine incorporation assays. Furthermore, ISO treatment promoted cell
      apoptosis, as demonstrated by flow cytometry, nucleosomal fragmentation and
      caspase-3 activity assays. Collectively, the present results suggest that COX2 is
      critical in the progression of LP, and ISO is a potential agent for LP therapy by
      impeding p38 MAPK/COX2 signaling.

PMID- 27882176
TI  - Effect of the interaction between atorvastatin and selective serotonin reuptake
      inhibitors on the blood redox equilibrium.
AB  - Cardiovascular disease and depression often occur simultaneously in the same
      patient. Long-term polypharmacotherapy can lead to drug-induced oxidative stress.
      Data concerning the effects of concomitant treatment with atorvastatin and
      selective serotonin reuptake inhibitors (SSRIs) are lacking. The aim of the
      present study was to examine oxidative stress parameters in the blood of rats
      after 28 days treatment with atorvastatin combined with fluoxetine or paroxetine.
      The study was carried out on male Wistar rats weighing 200-250 g. Aqueous
      solutions of atorvastatin (10 mg/kg), fluoxetine (10 mg/kg) and paroxetine (10
      mg/kg) were injected once a day for 28 days, separately or concomitantly. The
      activity of glutathione peroxidase (GPX) was determined in the whole blood,
      whereas the activity of glutathione reductase (GR) and the total antioxidant
      status (TAS) were determined in the serum. The results demonstrated that
      concomitant administration of atorvastatin with fluoxetine caused an increase in
      the GPX activity and the TAS. Atorvastatin administered to rats with paroxetine
      increased the activities of GPX and GR. In the groups of rats receiving
      atorvastatin or SSRIs separately, no statistically significant changes in the
      investigated parameters were observed. The changes that were detected may
      indicate an increase in endogenous antioxidant levels during the concomitant
      application of atorvastatin with SSRIs and thus a drug-drug interaction having an
      effect on the blood redox equilibrium.

PMID- 27882177
TI  - Catechol-O-methyltransferase promoter hypomethylation is associated with the risk
      of coronary heart disease.
AB  - Catechol-O-methyltransferase (COMT) gene variation is known to be associated with
      the risk of acute coronary events. The purpose of the present study was to
      investigate the contribution of COMT promoter methylation towards the risk of
      coronary heart disease (CHD). COMT methylation was evaluated in 48 CHD cases and
      48 well-matched non-CHD controls using bisulfite pyrosequencing technology. The
      results demonstrated that CHD cases had a significantly lower level of
      methylation at COMT CpG3 sites compared with the controls (33.77+/-5.71 vs.
      36.42+/-5.00%; P=0.018). Further analysis, according to gender, showed that CpG3
      methylation was associated with CHD in males (P=0.038) but not in females
      (P=0.253), suggesting that there is a gender disparity in the association between
      COMT methylation and CHD. In conclusion, it was determined that COMT CpG3
      hypomethylation is associated with an increased risk of CHD in males.

PMID- 27882178
TI  - Modulatory effects of feeding pregnant and lactating mice Rhodiola kirilowii
      extracts on the immune system of offspring.
AB  - Plants of Rhodiola genus are medicinal herbs that have a number of therapeutic
      properties, including anti-inflammatory and immunomodulatory activity. The
      present study aimed to determine whether the use Rhodiola kirilowii as an
      immunostimulant during pregnancy has an adverse effect on the development of the
      offspring immune system. Following mating, pregnant mice were placed in three
      groups that were fed during pregnancy and lactation with R. kirilowii aqueous
      extract (RKW; 20 mg/kg), R. kirilowii 50% hydro-alcoholic extract (RKW-A; 20
      mg/kg) or water (control group), receiving water. Following birth, offspring were
      given six weeks to develop prior to evaluation of their immune system.
      Morphometric and morphological examination of the spleen did not reveal any
      abnormalities or differences between the experimental and control groups.
      However, both RKW and RKW-A splenic lymphocytes presented a diminished
      proliferative response to concanavalin A. RKW spleen lymphocytes demonstrated
      increased metabolic activity following phytohaemagglutinin (PHA) stimulation,
      which was associated with a higher percentage of cluster of differentiation 4
      positive spleen cells and lower interleukin-17a (IL-17a) serum concentration. The
      RKW-A group exhibited a diminished proliferative response of spleen lymphocytes
      to PHA and lipopolysaccharide (LPS), and increased serum concentrations of IL-10
      and tumor necrosis factor-alpha (TNF-alpha). The progeny of mice fed with RKW-A
      extract demonstrated a significantly lower level of anti-SRBC antibody following
      immunization compared with progeny of the control (P=0.0305) and RKW (P=0.0331)
      groups. In conclusion, caution is recommended in the use of RKW and RKW-A
      extracts as immunostimulants in pregnancy.

PMID- 27882179
TI  - Acroosteolysis in systemic sclerosis: An insight into hypoxia-related
      pathogenesis.
AB  - Acro-osteolysis, or bony resorption of the terminal digital tufts, is a well
      recognized, but under-researched, feature of systemic sclerosis. The mechanisms
      that disturbs local homeostatic balance of bone formation and resorption in favor
      of osteoclast activation and pathological bone loss remain to be established.
      Vascular alterations and reduced capillary density impair tissue oxygenation in
      systemic sclerosis, and the resulting hypoxia might contribute directly to the
      disease progression. In this paper we summarize the current evidence for hypoxia
      as the common pathophysiological denominator of digital vasculopathy and enhanced
      osteoclastic activity in systemic sclerosis-associated acroosteolysis. The
      hypoxia-inducible transcription factor HIF-1alpha and VEGF signaling has a
      critical role in regulating osteoclastic bone-resorption and angiogenesis, and
      increased osteoclastogenesis and higher VEGF levels may contribute to
      acroosteolysis in systemic sclerosis. The cells of the osteoblast lineage also
      have important roles in angiogenic-osteogenic coupling. The research in this
      field might help limiting the disability associated with the disease.

PMID- 27882180
TI  - Concentrations of fetuin-A, osteoprotegerin and alpha-Klotho in patients with
      alcoholic liver cirrhosis.
AB  - The aim of the present study was to evaluate the concentrations of fetuin-A,
      osteoprotegerin (OPG) and alpha-Klotho protein in patients with alcoholic
      cirrhosis at different stages of the disease, and to demonstrate that fetuin-A,
      osteoprotegin and alpha-Klotho may be used as markers of the severity of
      cirrhosis. A total of 54 patients with alcoholic liver cirrhosis treated in
      various hospitals in the Lublin region of Poland were randomly enrolled. The
      control group consisted of 18 healthy individuals without liver disease, who did
      not drink alcohol. Serum levels of fetuin-A, OPG and alpha-Klotho were measured
      by ELISA kits. Levels of fetuin-A were significantly reduced in patients with
      alcoholic liver cirrhosis compared with the control group. OPG levels were higher
      in patients with alcoholic liver cirrhosis than in the controls, whereas the
      levels of alpha-Klotho were comparable in the cirrhosis and control groups. No
      statistically significant differences in the concentrations of fetuin-A, OPG and
      alpha-Klotho protein were demonstrated according to type of liver cirrhosis. The
      findings of the present study revealed a significant negative correlation between
      the level of alpha-Klotho protein and C-reactive protein in the patients with
      alcoholic liver cirrhosis. Concentrations of fetuin-A were lower, whereas those
      of OPG were higher, in the alcoholic liver cirrhosis group compared with the
      control group. Fetuin-A, OPG and alpha-Klotho may not be good indicators of liver
      cirrhosis severity. In conclusion, fetuin-A and OPG may be used in the diagnosis
      of liver cirrhosis.

PMID- 27882181
TI  - Angiogenin is upregulated during the alloreactive immune response and has no
      effect on the T-cell expansion phase, whereas it affects the contraction phase by
      inhibiting CD4+ T-cell apoptosis.
AB  - Under growth conditions, angiogenin is translocated into the nucleus, where it
      enhances ribosomal RNA transcription, facilitating increased protein synthesis
      and cellular proliferation. During stress conditions, angiogenin is sequestered
      in the cytoplasm, where it cleaves transfer RNA (tRNA) to produce tRNA-derived,
      stress-induced small RNAs (tiRNAs) that inhibit global protein synthesis, but
      increase the translation of anti-apoptotic factors. In the present study, the
      role of angiogenin in the human alloreactive immune response was evaluated using
      mixed lymphocyte reactions (MLRs) and neamine, an inhibitor of angiogenin nuclear
      translocation. In MLRs, angiogenin production was significantly (P<0.001)
      increased compared with resting peripheral blood mononuclear cells. The addition
      of neamine had no effect on cell proliferation, but did significantly (P<0.001)
      increase expression of Bcl-2-associated X protein and protein levels of activated
      caspase-3 in CD4+ T-cells isolated from the MLRs, indicating that angiogenin
      reduces apoptosis. In conclusion, angiogenin is upregulated during the
      alloreactive immune response, in which it does not affect the T-cell expansion
      phase, but inhibits the T-cell contraction phase by protecting against CD4+ T
      cell apoptosis.

PMID- 27882182
TI  - Disease progression in Chinese patients with hepatitis C virus RNA-positive
      infection via blood transfusion.
AB  - The majority of patients with hepatitis C virus (HCV) in China were infected via
      blood transfusion prior to the year 1996. In this systematic retrospective cohort
      study, disease progression in 804 consecutive patients with transfusion-acquired
      HCV is investigated. In addition, the occurrence of compensated cirrhosis,
      decompensated cirrhosis and hepatocellular carcinoma (HCC) is analyzed among
      these patients, along with the risk factors for disease progression. Patients
      with cirrhosis or HCC were classified as the serious development group (SD group)
      and the remaining patients with chronic hepatitis were classified as the
      hepatitis group (H group). Significant differences were found between the two
      groups in age at the time of infection, duration of infection and age at the time
      of observation. SD group patients were significantly older at the time of
      transfusion (33.73 vs. 23.56 years; P<0.001), with a significantly longer mean
      duration of HCV infection (21.88 vs. 21.15 years; P=0.029) compared with that in
      the H group. Male gender and age at the time of transfusion were significant risk
      factors for HCC (OR=2.48, P=0.031 and OR=1.07, P=0.002, respectively). Age was a
      significant risk factor for disease progression in older Chinese patients with
      transfusion-acquired HCV, and there were significant differences in the
      prevalence of compensated cirrhosis, decompensated cirrhosis and HCC between the
      age groups (P<0.001), suggesting that more patients with HCV may develop
      cirrhosis or HCC in their third and fourth decades of infection. Results of the
      present study will be helpful for predicting disease progression in Chinese
      patients with HCV infected via blood transfusion.

PMID- 27882183
TI  - Psychiatric symptoms and limb tremors associated with central pontine
      myelinolysis: A case of alcoholism without hyponatremia.
AB  - Central pontine myelinolysis (CPM), also known as osmotic demyelination syndrome,
      is a rare demyelinating disorder characterized by the loss of myelin in the
      center of the basis pontis. In this case report, an alcoholic patient with CPM
      and acquired demyelinating lesion of the basis pontis is described. The patient
      is a 70 year-old woman who presented with intermittent psychiatric symptoms and
      limb tremors following two months of alcohol abuse. During admission, magnetic
      resonance imaging (MRI) revealed hyperintensity on T2 weighted images and fluid
      attenuated inversion-recovery imaging in the central pons without contrast
      enhancement. The patient's symptoms gradually improved following conservative
      treatment with vitamins B1 and B12. The one month follow-up MRI showed a
      significant reduction of the pontine injury.

PMID- 27882185
TI  - Erratum: Carcinoma-like nonfunctional pheochromocytoma in the right adrenal
      gland: A case report.
AB  - [This corrects the article DOI: 10.3892/ol.2016.4776.].

PMID- 27882186
TI  - Erratum: Oncogenic role of the Notch pathway in primary liver cancer (Review).
AB  - [This corrects the article DOI: 10.3892/ol.2016.4609.].

PMID- 27882184
TI  - Phosphorylation of osteopontin has proapoptotic and proinflammatory effects on
      human knee osteoarthritis chondrocytes.
AB  - The aim of the present study was to investigate the effects of phosphorylated
      osteopontin (p-OPN) on apoptosis and pro-inflammatory cytokine expression in
      human knee osteoarthritis (OA) chondrocytes. Human knee OA chondrocytes obtained
      from patients who underwent total knee arthroplasty were treated with p-OPN, OPN
      or buffer. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR)
      and western blot analysis were used to assess the expression levels of
      proinflammatory factors, including interleukin (IL)-1beta, tumor necrosis factor
      (TNF)-alpha, IL-6 and nuclear factor (NF)-kappaB. Apoptosis of human knee OA
      chondrocytes was detected by Annexin V-fluorescein isothiocyanate/propidium
      iodide flow cytometry. Compared with the controls, chondrocytes treated with OPN
      exhibited higher mRNA and protein expression levels of proinflammatory factors
      (IL-1beta, TNF-alpha, IL-6 and NF-kappaB), and a higher percentage of apoptotic
      chondrocytes. Furthermore, chondrocytes treated with p-OPN exhibited the highest
      mRNA and protein expression levels of proinflammatory factors (IL-1beta, TNF
      alpha, IL-6, NF-kappaB) and the highest percentage of apoptotic chondrocytes. p
      OPN induces chondrocyte apoptosis and proinflammatory factor release, which
      suggests that p-OPN may contribute to OA pathogenesis, and inhibition of p-OPN
      may provide a novel effective strategy to slow or halt OA progression.

PMID- 27882188
TI  - Determinants of translation ambiguity: A within and cross-language comparison.
AB  - Ambiguity in translation is highly prevalent, and has consequences for second
      language learning and for bilingual lexical processing. To better understand this
      phenomenon, the current study compared the determinants of translation ambiguity
      across four sets of translation norms from English to Spanish, Dutch, German and
      Hebrew. The number of translations an English word received was correlated across
      these different languages, and was also correlated with the number of senses the
      word has in English, demonstrating that translation ambiguity is partially
      determined by within-language semantic ambiguity. For semantically-ambiguous
      English words, the probability of the different translations in Spanish and
      Hebrew was predicted by the meaning-dominance structure in English, beyond the
      influence of other lexical and semantic factors, for bilinguals translating from
      their L1, and translating from their L2. These findings are consistent with
      models postulating direct access to meaning from L2 words for moderately
      proficient bilinguals.

PMID- 27882187
TI  - Child, Teacher and Parent Perceptions of the FRIENDS Classroom-Based Universal
      Anxiety Prevention Programme: A Qualitative Study.
AB  - School-based mental health prevention programmes can be effective but their
      adoption within schools will depend on their social acceptability. We report a
      qualitative evaluation summarising the views of children (115), parents (20) and
      school staff (47) about a universal school-based anxiety prevention programme
      FRIENDS. This study was conducted as part of a large scale randomised controlled
      trial (n = 1362) involving 40 schools in the UK providing primary education to
      children aged 7-11. Reported overall experience of the programme was very
      positive, with all three major components of the cognitive behaviour therapy
      programme (emotional, cognitive, and behavioural) being accepted well and
      understood by children. The programme was considered to be enjoyable and valuable
      in teaching children important skills, particularly emotional regulation and
      coping. Children provided examples of using the skills learned during FRIENDS to
      manage their emotions and solve problems. However, teachers were concerned that
      the programme overlapped with the current school curriculum, required additional
      time and almost half were unable to identify any tangible changes in the
      children's behaviour. Whilst this paper provides evidence to support the social
      validity of the FRIENDS anxiety prevention programme, the concerns raised by
      teachers question the longer-term sustainability of the programme.

PMID- 27882189
TI  - Successful Treatment of Resistant Hypertension by Means of Chronic Renal Artery
      Occlusion Revascularization in a Fragile Patient.
AB  - BACKGROUND: Renal artery stenosis is a common cause of secondary hypertension
      refractory to medical therapy. Percutaneous angioplasty along with metallic stent
      placement has been described as an effective treatment for revascularization of
      the renal artery. CASE REPORT: A 54-year-old woman affected by paranoid
      schizophrenia with a history of hypertension and chronic renal failure due to
      renal artery occlusion was treated by endovascular recanalization and stent
      placement that resulted in improvement of renal function and control of
      hypertension. Laboratory studies 4 months after the revascularization revealed
      blood creatinine decrease gradually from 8.57 mg/dL to 3 mg/dL. CONCLUSIONS:
      Revascularization with stenting has proven to be a safe and effective procedure
      in the treatment of total renal artery occlusion which also led to a significant
      relief at a psychological level.

PMID- 27882190
TI  - Family Sources of Sexual Health Information, Primary Messages, and Sexual
      Behavior of At-Risk, Urban Adolescents.
AB  - BACKGROUND: Sources of sexual health information exert strong influence on
      adolescents' sexual behavior. PURPOSE: The current study was undertaken to
      understand how family serve as sexual information sources, the messages
      adolescents recall from family, and how family learning experiences affect sexual
      behavior among at-risk adolescents. METHODS: Individual interviews were conducted
      with 69 teens, ages 15-18 years, from an alternative high school and a juvenile
      correctional facility to capture adolescents' early sexual health learning
      experiences involving family and evaluate their association with teens' recent
      sexual behavior. Sexual learning narratives were compared among gender and sexual
      experience groups. RESULTS: Many participants identified family as sexual health
      information sources. Primary messages recalled: risks of sex, protection, and
      relationship advice. Many adolescents portrayed learning experiences as negative,
      cautionary, lacking detail and not always balanced with positive messages.
      Participants who reported four or more sexual risks were the only group to
      identify pornography as a sexual health information source. Participants who
      reported fewer than four sexual risks were most likely to identify family sexual
      health information sources. DISCUSSION: Participants identified family members as
      sources of sexual health information, with variations by gender.
      Negative/cautionary messages require teens to seek additional sexual information
      elsewhere (primarily friends/media). Males, in particular, appear to often lack
      familial guidance/education. TRANSLATION TO HEALTH EDUCATION PRACTICE: Sexual
      health messages should be tailored to adolescents' needs for practical and sex
      positive guidance regarding mechanics of sex and formation of healthy
      relationships, and balanced with cautions regarding negative consequences.

PMID- 27882192
TI  - Next-Generation Antibody-Drug Conjugates (ADCs) for Cancer Therapy.

PMID- 27882193
TI  - Expanding the Reach of Antibody-Drug Conjugates.
AB  - Antibody-drug conjugates (ADCs) represent an emerging new paradigm in cancer
      therapy. The approval of two ADCs has spurred considerable interest in this area
      of research, and over 55 ADCs are currently in clinical testing. In order to
      improve the clinical success rate of ADC therapy, all three components of the
      ADC: the antibody, linker, and payload have to be optimized. While considerable
      improvements have been made in antibody properties and target selection,
      medicinal chemistry efforts have lagged behind, and there is a significant need
      for innovation in linker design and payloads.

PMID- 27882191
TI  - Protective Effects of Hydrogen Sulfide in the Ageing Kidney.
AB  - Aims. The study aimed to examine whether hydrogen sulfide (H2S) generation
      changed in the kidney of the ageing mouse and its relationship with impaired
      kidney function. Results. H2S levels in the plasma, urine, and kidney decreased
      significantly in ageing mice. The expression of two known H2S-producing enzymes
      in kidney, cystathionine gamma-lyase (CSE) and cystathionine-beta-synthase (CBS),
      decreased significantly during ageing. Chronic H2S donor (NaHS, 50 MUmol/kg/day,
      10 weeks) treatment could alleviate oxidative stress levels and renal tubular
      interstitial collagen deposition. These protective effects may relate to
      transcription factor Nrf2 activation and antioxidant proteins such as HO-1,
      SIRT1, SOD1, and SOD2 expression upregulation in the ageing kidney after NaHS
      treatment. Furthermore, the expression of H2S-producing enzymes changed with
      exogenous H2S administration and contributed to elevated H2S levels in the ageing
      kidney. Conclusions. Endogenous hydrogen sulfide production in the ageing kidney
      is insufficient. Exogenous H2S can partially rescue ageing-related kidney
      dysfunction by reducing oxidative stress, decreasing collagen deposition, and
      enhancing Nrf2 nuclear translocation. Recovery of endogenous hydrogen sulfide
      production may also contribute to the beneficial effects of NaHS treatment.

PMID- 27882194
TI  - Optimization of Tubulysin Antibody-Drug Conjugates: A Case Study in Addressing
      ADC Metabolism.
AB  - As part of our efforts to develop new classes of tubulin inhibitor payloads for
      antibody-drug conjugate (ADC) programs, we developed a tubulysin ADC that
      demonstrated excellent in vitro activity but suffered from rapid metabolism of a
      critical acetate ester. A two-pronged strategy was employed to address this
      metabolism. First, the hydrolytically labile ester was replaced by a carbamate
      functional group resulting in a more stable ADC that retained potency in cellular
      assays. Second, site-specific conjugation was employed in order to design ADCs
      with reduced metabolic liabilities. Using the later approach, we were able to
      identify a conjugate at the 334C position of the heavy chain that resulted in an
      ADC with considerably reduced metabolism and improved efficacy. The examples
      discussed herein provide one of the clearest demonstrations to-date that site of
      conjugation can play a critical role in addressing metabolic and PK liabilities
      of an ADC. Moreover, a clear correlation was identified between the
      hydrophobicity of an ADC and its susceptibility to metabolic enzymes.
      Importantly, this study demonstrates that traditional medicinal chemistry
      strategies can be effectively applied to ADC programs.

PMID- 27882195
TI  - Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate
      Pyrrolobenzodiazepine Dimer Payload.
AB  - Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of
      antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent
      antitumor activity with desirable physicochemical properties such as favorable
      hydrophobicity and improved conjugation characteristics. One of the reactive
      imines was capped with a cathepsin B-cleavable valine-alanine linker. A robust
      synthetic route was developed to allow the production of tesirine on clinical
      scale, employing a flexible, convergent strategy. Tesirine was evaluated in vitro
      both in stochastic and engineered ADC constructs and was confirmed as a potent
      and versatile payload. The conjugation of tesirine to anti-DLL3 rovalpituzumab
      has resulted in rovalpituzumab-tesirine (Rova-T), currently under evaluation for
      the treatment of small cell lung cancer.

PMID- 27882196
TI  - Linker Immolation Determines Cell Killing Activity of Disulfide-Linked
      Pyrrolobenzodiazepine Antibody-Drug Conjugates.
AB  - Disulfide bonds could be valuable linkers for a variety of therapeutic
      applications requiring tunable cleavage between two parts of a molecule (e.g.,
      antibody-drug conjugates). The in vitro linker immolation of beta-mercaptoethyl
      carbamate disulfides and DNA alkylation properties of associated payloads were
      investigated to understand the determinant of cell killing potency of anti-CD22
      linked pyrrolobenzodiazepine (PBD-dimer) conjugates. Efficient immolation and
      release of a PBD-dimer with strong DNA alkylation properties were observed
      following disulfide cleavage of methyl- and cyclobutyl-substituted disulfide
      linkers. However, the analogous cyclopropyl-containing linker did not immolate,
      and the associated thiol-containing product was a poor DNA alkylator. As
      predicted from these in vitro assessments, the related anti-CD22 ADCs showed
      different target-dependent cell killing activities in WSU-DLCL2 and BJAB cell
      lines. These results demonstrate how the in vitro immolation models can be used
      to help design efficacious ADCs.

PMID- 27882197
TI  - Site-Specific Tandem Knoevenagel Condensation-Michael Addition To Generate
      Antibody-Drug Conjugates.
AB  - Expanded ligation techniques are sorely needed to generate unique linkages for
      the growing field of functionally enhanced proteins. To address this need, we
      present a unique chemical ligation that involves the double addition of a
      pyrazolone moiety with an aldehyde-labeled protein. This ligation occurs via a
      tandem Knoevenagel condensation-Michael addition. A pyrazolone reacts with an
      aldehyde to generate an enone, which undergoes subsequent attack by a second
      pyrazolone to generate a bis-pyrazolone species. This rapid and facile ligation
      technique is performed under mild conditions in the absence of catalyst to
      generate new architectures that were previously inaccessible via conventional
      ligation reactions. Using this unique ligation, we generated three site
      specifically labeled antibody-drug conjugates (ADCs) with an average of four
      drugs to one antibody. The in vitro and in vivo efficacies along with
      pharmacokinetic data of the site-specific ADCs are reported.

PMID- 27882198
TI  - Design, Synthesis, and Cytotoxic Evaluation of Novel Tubulysin Analogues as ADC
      Payloads.
AB  - The tubulysin class of natural products has attracted much attention from the
      medicinal chemistry community due to its potent cytotoxicity against a wide range
      of human cancer cell lines, including significant activity in multidrug-resistant
      carcinoma models. As a result of their potency, the tubulysins have become an
      important tool for use in targeted therapy, being widely pursued as payloads in
      the development of novel small molecule drug conjugates (SMDCs) and antibody-drug
      conjugates (ADCs). A structure-based and parallel medicinal chemistry approach
      was applied to the synthesis of novel tubulysin analogues. These efforts led to
      the discovery of a number of novel and potent cytotoxic tubulysin analogues,
      providing a framework for our simultaneous report, which highlights the discovery
      of tubulysin-based ADCs, including use of site-specific conjugation to address in
      vivo stability of the C-11 acetate functionality.

PMID- 27882199
TI  - Straightforward Glycoengineering Approach to Site-Specific Antibody
      Pyrrolobenzodiazepine Conjugates.
AB  - Antibody-drug conjugates (ADCs) have become a powerful platform to deliver
      cytotoxic agents selectively to cancer cells. ADCs have traditionally been
      prepared by stochastic conjugation of a cytotoxic drug using an antibody's native
      cysteine or lysine residues. Through strategic selection of the mammalian
      expression host, we were able to introduce azide-functionalized glycans onto a
      homogeneously glycosylated anti-EphA2 monoclonal antibody in one step.
      Conjugation with an alkyne-bearing pyrrolobenzodiazepine dimer payload (SG3364)
      using copper-catalyzed click chemistry yielded a site-specific ADC with a drug-to
      antibody ratio (DAR) of four. This ADC was compared with a glycoengineered DAR
      two site-specific ADC, and both were found to be highly potent against EphA2
      positive human prostate cancer cells in both an in vitro cytotoxicity assay and a
      murine tumor xenograft model.

PMID- 27882200
TI  - Calcification in Globus Pallidus and Putamen of Multiple Sclerosis Patients
      Versus Healthy Subjects Using Quantitative Susceptibility Mapping.
AB  - BACKGROUND: Calcification has been well reported in basal ganglia and it grows
      rapidly in globus pallidus (GP) followed by putamen (PUT) and caudate nucleus
      because of their high metabolic rate and displays high susceptibility effects.
      Therefore, the current study focused on magnetic susceptibility effect of calcium
      content in normal and diseased tissue due to metabolic changes. OBJECTIVES: To
      evaluate calcium content in GP and PUT structures of multiple sclerosis (MS)
      patients versus healthy subjects using quantitative susceptibility mapping.
      PATIENTS AND METHODS: We compared 10 MS patients with mean age of 48.3 years
      (standard deviation [SD]=11.89) with 10 healthy subjects with mean age of 39.6
      years (SD=11.52). Scanning of subjects was performed with high resolution
      (0.5*0.5*2 mm3) using susceptibility weighted imaging sequence on 3 Tesla (Trio
      Siemens, Erlangen, Germany). Data was processed in homemade SPIN software to
      produce susceptibility mapping. Threshold was set in healthy subjects to detect
      calcium content in PUT and GP structures. RESULTS: Magnetic susceptibility(x) of
      calcium content was assessed by number of pixels induced by GP and PUT in MS
      patients as well as healthy subjects. Two sample t-test was used to assess the
      difference between susceptibilities of GP and PUT of MS patients (P = 0.06, P >
      0.05). Susceptibilities of GP and PUT also showed P = 0.3 in healthy subjects.
      One way analysis of variance was used to assess the difference of
      susceptibilities in four variables of both populations. Insignificant results (P
      = 0.7, P > 0.05) were found among four variables. There was no statistically
      significant difference between magnetic susceptibilities of both populations.
      CONCLUSION: Statistical analysis of susceptibilities of MS patients versus
      healthy subjects found no excess deposition of calcium content in deep gray
      matter of MS patients. Calcification may not be considered as a biomarker of
      prognosis in MS.

PMID- 27882201
TI  - A Case of Fibrovascular Polyp of the Stomach: Sonographic and Computed
      Tomographic Findings.
AB  - Fibrovascular polyps are rare, pedunculated, tumor-like lesions that are usually
      found in the esophagus; occurrence in the stomach is very rare. To our knowledge,
      sonographic and CT findings of a fibrovascular polyp in the stomach have never
      been reported. Here, we report a case of a fibrovascular polyp that was
      identified in the gastric antrum and prolapsed into the duodenal bulb. Sonography
      revealed a hyperechoic polypoid mass in the gastric antrum, which prolapsed into
      the duodenal bulb upon a change in the patient's position. CT also revealed a
      pedunculated polypoid mass with an inner fatty component.

PMID- 27882202
TI  - Computed Tomography Colonography Phantom: Construction, Validation and Literature
      Review.
AB  - BACKGROUND: Several dedicated computed tomography (CT) colonography phantoms have
      been described previously. OBJECTIVES: To compare their pros and cons and
      describe the construction of a dedicated phantom that can be easily manufactured.
      MATERIALS AND METHODS: We found 15 different phantom designs by literature search
      and compared their advantages and disadvantages based on their description and
      images. We tested various materials for density and mechanical properties and
      constructed a phantom from polypropylene pipes (30 mm and 50 mm in diameter, 52
      cm in length). Haustral folds were created by heat shaping and 39 intermediate
      sessile polyps with a target size of 6-10 mm and two flat lesions were created
      from silicone. Nine polyps were attached to a fold. The model was placed in a 30
      cm barrel filled with water to simulate attenuation of human body. Attenuation of
      polyps was compared to intermediate polyps found in patients. RESULTS: None of
      the earlier colonic phantoms found in the literature incorporated all the
      properties that would ensure both reproducibility and validity of the model
      (including a rigid wall, density of the wall and polyps similar to human colon,
      at least two levels of distension and durability). In the present phantom, the
      average size of sessile polyps was 8.6 +/- 0.9 mm and their density was 53 +/- 24
      HU. We found no significant difference in polyp density between simulated polyps
      in the phantom and polyps in human subjects (P = 0.70). All polyps, with the
      exception of one flat lesion, were detected by computer aided detection.
      CONCLUSION: We constructed and validated a CT colonography phantom with correct
      density allowing performance of reproducible experiments.

PMID- 27882203
TI  - Effectiveness of Emotion Regulation Training on the Reduction of Craving in Drug
      Abusers.
AB  - BACKGROUND: Emotion regulation appears to provide individuals with a doubled
      ability to avoid drug relapse and assists with the control of temptation to
      reuse, which is a type of tendency-avoidance conflict. The present study aims to
      investigate the effect of Gross model-based emotion regulation training on the
      reduction of craving beliefs in drug-addicted people. METHODS: The present study
      was a quasi-experimental design. This was a pre- and post-test design that
      consisted of control and experimental groups. The study population comprised all
      addicted individuals who visited addiction treatment clinics in Marivan, Iran.
      About 30 drug-addicted individuals by the random selection method were chosen.
      Participants were randomly assigned to either the experimental or control groups.
      Results were analyzed by univariate covariance analysis. FINDINGS: Gross model
      based emotion regulation training reduced signs and beliefs associated with
      temptation in drug-addicted people (P < 0.05). CONCLUSION: Considering the
      present study's findings, we recommend that addiction treatment centers teach
      strategies of emotion regulation to drug-addicted people by establishing
      workshops with the intent to reduce temptation signs.

PMID- 27882204
TI  - Comparison of Quantitative and Qualitative Dermatoglyphic Characteristics of
      Opium Addicts with Healthy Individuals.
AB  - BACKGROUND: Recreational drugs have a significant impact on the lives of drug
      users, their close families andfriends, as well as their society. Social,
      psychological, biological, and genetic factors could make a personmore prone to
      using recreational drugs. Finger and A-B ridges (dermatoglyphics) are formed
      during the firstand second trimesters of fetal development, under the influence
      of environmental and genetic factors. Theaim of our study was to investigate and
      evaluate a possible link between dermatoglyphics and opium usage. METHODS: The
      pattern of dermatoglyphics - finger and A-B prints - obtained from a group of
      opium users(121 patients) was compared to those obtained from a group of opium
      non-users (121 patients) from Birjand,Iran. The results were analyzed using chi
      square, t and Mann-Whitney tests. FINDINGS: The results showed that although A-B
      ridges of palms and fingers in our study group were highercompared to the control
      group, there was no significant difference between these groups. The only
      significantdifference was the fingerprint patterns of the left ring finger in the
      study group, which lacked the arch patternand had less loop patterns. The
      dominant type of fingerprint in the left ring finger was the whorl. In ouropium
      user group, the arch and loop fingerprint patterns were heterogeneous and
      significantly different incomparison with the control group (P < 0.01).
      CONCLUSION: These findings suggest that a genetic factor may increase the
      predisposition to recreational drugusage. Further research is required to confirm
      this possible impact of genetic factors on the addiction process.

PMID- 27882205
TI  - Sleep Disorders in Methadone Maintenance Treatment Volunteers and Opium-dependent
      Patients.
AB  - BACKGROUND: The relationship between substance use and sleep is bidirectional.
      Substance use directly causessleep disturbances, and sleep problems are a
      critical factor in substance-use relapse. METHODS: This study evaluated sleep
      disorders in 65 methadone maintenance treatment (MMT) patients, and61 opium
      dependent patients who did not receive any treatment between September 2011 and
      July 2012 inKermanshah, Iran. Both groups filled out the Pittsburgh Sleep Quality
      Index (PSQI) and Global SleepAssessment Questionnaire (GSAQ). FINDINGS: Sleep
      disorders were remarkably similar in both groups: 78.5% of MMT patients and 87.7%
      ofopium-dependent patients suffered from sleep problems. Sleep disorders in the
      opium-dependent groupwere remarkably higher and more prominent. CONCLUSION:
      Compared to opium, MMT does not have as many negative effects on sleep and is
      more effectivein mitigating sleep problems.

PMID- 27882206
TI  - Willingness to Receive Treatment for Hepatitis C among Injecting Drug Users on
      Methadone Program: Implications for Education and Treatment.
AB  - BACKGROUND: Hepatitis C virus (HCV) is common among people who inject drugs
      (PWID) on methadoneprogram in Iran (Persia). However, a few PWID on methadone
      program report willingness to receive HCVtreatment. This study aimed to assess
      the factors which were associated with willingness to receive HCVtreatment in a
      group of PWID on methadone program in Iran. METHODS: We surveyed 187 PWID at
      seven drops in centers in Tehran, Iran. Details of demographiccharacteristics,
      drug use, injection, HCV, and drug treatment history were collected using a 25
      itemquestionnaire. Participants were serologically tested for the current status
      of HCV. FINDINGS: The study found that 28.3% of the participants were HCV
      seropositive. In total, 49.1% of theparticipants reported unwillingness to
      receive HCV treatment. Awareness of current HCV status [odds ratio(OR) = 3.43;
      95% confidence interval (CI): 1.33-7.26; P < 0.050]; adequate knowledge of HCV
      treatmentcenters in the community (OR = 3.9; 95% CI: 1.24-5.38; P < 0.050);
      participation in an educational programon HCV (OR = 2.9; 95% CI: 2.33-8.56; P <
      0.001) and recent participation in the meetings of self-helpgroups (OR = 4.6; 95%
      CI: 3.43-9.33; P < 0.001) were significantly associated with current willingness
      toreceive HCV treatment. CONCLUSION: The study results indicate that awareness of
      HCV status and the provision of adequate HCVeducation via different information
      centers can be associated with an increased willingness for HCVtreatment among
      PWID on methadone program. Conducting more research is suggested to assess
      theefficacy of educational programs and self-help groups in facilitating HCV
      treatment among PWID onmethadone program.

PMID- 27882207
TI  - Living with Addicted Men and Codependency: The Moderating Effect of Personality
      Traits.
AB  - BACKGROUND: This study aimed to determine the moderating effect of personality
      traits on the relationship between living with an addicted man and codependency.
      METHODS: We selected 140 women (70 wives of addicted men and 70 wives of non
      addicted men) through convenience sampling method and asked them to complete
      Spann-Fischer Codependency Scale and NEO-Five Factor Inventory. FINDINGS:
      Codependency score was significantly higher among addicted men's wives. In
      addition, for these women, there was a strong positive correlation between
      codependency and neuroticism as well. Multiple regression analysis confirmed the
      significant interaction effects of being an addict's wife and personality traits
      of neuroticism, openness and agreeableness on codependency. CONCLUSION: Not all
      addicts' wives experienced codependency; women with a high level of neuroticism
      and low level of openness and agreeableness were more vulnerable to the stress of
      living with an addict and to codependency.

PMID- 27882209
TI  - Marketed New Drug Delivery Systems for Opioid Agonists/Antagonists
      Administration: A Rapid Overview.
AB  - Novel drug delivery systems for controlled-release of opioid agonists as a long
      time painkillers or opioid antagonists for opium, heroin, and alcohol addiction
      are under development or in clinical use today. In this article, the field of
      "new drug delivery systems" is momentarily reviewed from the viewpoint of the
      marketed opioid agonists/antagonists dosage forms today.

PMID- 27882208
TI  - Maternal Separation and the Risk of Drug Abuse in Later Life.
AB  - Maternal separation (MS) is defined as the termination of the continuity of
      mother-child relationship after the relationship is established. Although MS and
      maternal deprivation are different in terms of their definitions, these two terms
      are usually used interchangeably. This review aims to investigate the effect of
      MS on drug intake in adulthood. It has been proved that animal models are helpful
      in evaluating the effects of MS on drug intake risk in adulthood. There are
      relatively acceptable studies in this field on some drugs such as morphine,
      ethanol, and cocaine. However, very few animal studies, or even no animal study,
      have been conducted on some other drugs. The majority of these studies have
      considered MS as a risk factor for drug intake in adulthood. Different mechanisms
      are proposed for this phenomenon. Brain reward pathways are one of the main
      exploratory pathways of this process. Despite the importance of the issue, no
      human study with a specific concentration on investigating the relationship
      between MS and drug abuse in later life was found. Causal studies are warranted
      on humans to investigate the effect of MS on drug intake in later life.

PMID- 27882210
TI  - Factors Affecting Hookah Smoking Trend in the Society: A Review Article.
AB  - BACKGROUND: An increase in hookah smoking is considered to be a serious health
      problem in societies withdifferent cigarette smoking patterns. Thus, determinants
      of increase in this behavior are needed to beidentified. This study aimed to
      review the articles related to the causes of hookah smoking in the society.
      METHODS: This study reviewed the scientific references of authentic databases and
      journals, including Web ofScience, PubMed, Iranian Databases, Elsevier, Embase,
      Scopus, MEDLINE, CINAHL, CDC, and WorldHealth Organization (WHO). Overall, 84
      scientific studies conducted during 1990-2015 were collected. FINDINGS: Several
      studies on the prevalence of smoking hookah and its associated factors in the
      societysuggested that numerous factors played a role in interest in smoking
      hookah. The most common reasons forindividuals' inclination to smoke hookah were
      positive viewpoints toward smoking hookah, wrong beliefsabout its low risks,
      presumed lack of addiction, social acceptance, ease of access, wrong cultural
      habits, andregulative weakness. CONCLUSION: Evidence indicated that a large
      spectrum of individual and social factors was effective in variouslevels of
      hookah consumption. Besides, it seems that single-component interventions and
      those solely basedon individual factors could not result in effective prevention.
      On the other hand, interventions based onecological approaches are suggested in
      this regard. Overall, it is essential to focus on the exclusion of
      positiveviewpoints toward hookah, develop the ability to say "no," relaxation,
      and resistance against temptations tosmoke hookah, culturalization, and
      regulation of strong laws.

PMID- 27882211
TI  - Novel perspectives on the role of the human microbiota in regenerative medicine
      and surgery.
AB  - Plastic surgery is transitioning from a fine craftsmanship to a regenerative
      science. In wound healing, the role of microorganisms is no longer considered to
      be just counteracting, but also promoting. Furthermore, host-microbe interactions
      are essential for numerous aspects of normal mammalian physiology, from metabolic
      activity to immune homeostasis. Each area of the human body hosts a unique
      microbial community, and the composition of microbiota is dependent on the host,
      age and the anatomical area, and it changes according to the characteristics of
      the microenvironment. Every squared centimeter of skin contains ~1 billion
      bacteria. The majority of microorganisms of the skin are commensal or temporary
      passing members. Skin flora mechanisms interacting or influencing the human
      physical skin barrier are not well defined. Resident skin bacteria provide the
      first line of defence against potentially dangerous pathogens and produce small
      molecules that influence their microbial neighbours. Furthermore, the microbiota
      activates and assists innate immunity and influences adaptive immunity. Various
      types of immune and non-immune cells contribute to wound healing. The
      proliferative phase of wound healing is inversely proportional to the extent of
      the post-traumatic inflammatory reaction. Topical bacterial lipopolysaccharide
      application markedly affects wound healing by accelerating the resolution of
      inflammation, increasing macrophage infiltration, enhancing collagen synthesis
      and altering the secretion of mediators involved in skin regeneration. Various
      studies have investigated the biological contents of thermal spring waters, and
      their anti-inflammatory and immune protective roles. In addition, the
      regenerative properties of thermal spring waters were analysed in an experimental
      animal wound model. The areas treated with thermal water healed faster than the
      areas treated with conventional dressings, and exhibited a collagen and elastic
      fiber network comparable with the normal skin. Thus, the microbial environment
      may be considered as a potential tool in regenerative medicine and surgery.

PMID- 27882212
TI  - Resveratrol and exercise.
AB  - Although it is recommended for a healthy lifestyle, moderate exercise is known to
      lead to oxidative stress, inflammation and muscle injury. Hence there are efforts
      to develop dietary strategies to counter the oxidative stress caused by physical
      activity. Recently, there has been an interest in the capability of resveratrol
      (RES) to modulate physical performance and prevent oxidative stress. Despite the
      inconsistency among reports regarding the topic, it has been suggested that RES
      delays fatigue by hindering lipid peroxidation. It is hypothesized that RES
      administration produces favorable effects on hepatic cell rejuvenation, exerts a
      regulatory effect on glucose metabolism, and preserves liver glycogen reserves
      that are diminished during physical activity. Consequently, there is a growing
      interest in the association between RES and exercise. The aim of the current
      review is to interpret the association between RES and exercise.

PMID- 27882213
TI  - Endometriosis research using capture microdissection techniques: Progress and
      future applications.
AB  - Endometriosis is a common gynecological disease with high prevalence, while its
      etiology and pathophysiology have remained to be fully elucidated. Previous
      evidence suggested that this disorder may be in part or completely of somatic
      origin. However, traditional endometrial samples may not be ideal for
      investigation, as target cells, including epithelial and stromal cells, in
      endometriotic lesions are too sparse to be analyzed. Recently, capture
      microdissection techniques have been used to overcome these limitations and
      eliminate tissue heterogeneity in endometriosis research. Therefore, the present
      review summarized the alterations in epithelial and stromal cells in
      endometriosis tissues isolated through capture microdissection, outlined recent
      progress and provided directions for future investigation of the pathogenesis of
      endometriosis.

PMID- 27882214
TI  - Efficacy and safety of different doses of evolocumab in reducing low-density
      lipoprotein cholesterol levels: A meta-analysis.
AB  - Evolocumab has been considered as an efficacious, safe and promising therapeutic
      modality for hypercholesterolemia and is associated with cardiovascular diseases.
      The efficacy and safety of two different doses of evolocumab were evaluated and
      the safety of evolocumab was compared with that of a placebo and ezetimibe.
      PubMed and EMBASE databases were searched and randomized controlled trials that
      examined the effect and safety of evolomucab compared with a placebo and
      ezetimibe were retrieved. Two authors independently performed article reviews and
      study quality evaluations. Odds ratios (ORs) were calculated using a fixed or
      random-effects model [95% confidence intervals (CIs)]. In the direct comparison,
      a significant reduction was observed in the muscle-associated events compared
      with ezetimibe [OR=0.54 (95% CI, 0.31-0.93); P (Z)=0.03, P (Q)=0.43, I2=0%]. In
      the adjusted indirect comparison of evolocumab 140 mg Q2W vs. evolocumab 420 mg
      Q4W, no significant differences in efficacy [OR=1.04 (95% CI, 0.55-1.99); P
      (Z)=0.90] or adverse events [OR=1.08 (95% CI, 0.66-1.74); P (Z)=0.76] were
      identified. The funnel plots of these direct comparison studies indicated that
      there was no publication bias. The results of this meta-analysis demonstrate that
      evolocumab significantly reduced low-density lipoprotein cholesterol levels, and
      no difference was noted between evolocumab 140 mg Q2W and evolocumab 420 mg Q4W.
      Furthermore, evolocumab had fewer muscle-associated events than ezetimibe.

PMID- 27882215
TI  - Epigenetic changes in peripheral leucocytes as biomarkers in intrauterine growth
      retardation rat.
AB  - Epigenetics plays an important role in the fetal origins of adult disease.
      Intrauterine growth retardation (IUGR) can cause increased histone acetylation of
      the endothelin-1 (ET-1) gene from pulmonary vascular endothelial cells or the
      whole lung tissue and persist into later life, likely resulting in increased risk
      of pulmonary hypertension or asthma later in life. However, little is known
      regarding the correlation of epigenetic changes between specific tissue and
      peripheral leucocytes. In the present study, an IUGR rat model was established by
      maternal nutrient restriction. Peripheral blood leucocytes were isolated to
      detect the ET-1 expression level. Chromatin immunoprecipitation was used to
      analyze histone modification of the ET-1 gene promoter. The ET-1 protein
      expression of leucocytes from the 1-week IUGR group was similar to that from the
      1-week control group. ET-1 protein expression of leucocytes from 10-week IUGR
      rats was obviously higher than that of the other groups (P<0.05). The levels of
      acetylated histone H3 in the ET-1 promoter of leucocytes from the 1-week IUGR
      rats were significantly higher than those from the age-matched control group
      (P=0.004). Furthermore, the trends continued <=10 weeks after birth. In
      conclusion, epigenetic modifications of leucocytes can in part reflect the
      epigenetic changes of lung tissue in IUGR rats. Epigenetics of peripheral
      leucocytes may be used as a biomarker for predicting the risk of the development
      of disease, and may be used as a surrogate to investigate the subsequent
      development of pulmonary vascular disease or asthma.

PMID- 27882216
TI  - Intake of kale suppresses postprandial increases in plasma glucose: A randomized,
      double-blind, placebo-controlled, crossover study.
AB  - Kale (Brassica oleracea var. acephala), a vegetable in the family Brassicaceae,
      has beneficial effects on health, including hypoglycemic effects. In our previous
      study with a limited number of subjects, intake of kale-containing food at a dose
      of 14 g decreased postprandial plasma glucose levels. In the present study, the
      effective dose of kale-containing food was investigated in a randomized, double
      blind, placebo-controlled, crossover trial. The trial was conducted on 42
      Japanese subjects aged 21-64 years with fasting plasma glucose levels of <=125
      mg/dl and 30-min postprandial plasma glucose levels of 140-187 mg/dl. The
      subjects consumed placebo or kale-containing food [7 or 14 g; low-dose (active-L)
      or high-dose (active-H) kale, respectively] together with a high-carbohydrate
      meal. At 30-120 min after the test meal intake, the plasma levels of glucose and
      insulin were determined. The postprandial plasma glucose levels in subjects with
      intake of active-L or active-H were significantly lower than those in subjects
      with intake of placebo, with the maximum plasma concentration (Cmax; 163+/-24
      mg/dl for active-L and 162+/-23 mg/dl for active-H compared with 176+/-26 mg/dl
      for placebo [values presented as means +/- standard deviation (SD); P<0.01]. The
      area under the plasma glucose concentration-time curve for 0-2 h (AUC0-2 h)
      values (means +/- SD) were significantly lower for active-L (268+/-43 mg/h/dl)
      and active-H (266+/-42 mg/h/dl) than for the placebo (284+/-43 mg/h/dl; P<0.05).
      No significant differences were identified in the postprandial plasma insulin
      levels between the three conditions. No adverse events associated with intake of
      either dose of kale were observed. Our findings suggest that intake of kale
      suppresses postprandial increases in plasma glucose levels at a single dose of 7
      g, and that a dose as high as 14 g is safe.

PMID- 27882217
TI  - Multiple effects of Xihuang pill aqueous extract on the Hs578T triple-negative
      breast cancer cell line.
AB  - The management of triple-negative breast cancer (TNBC) is challenging due to the
      aggressive behavior, lack of therapeutic options and relatively poor prognosis.
      Xihuang pill (XHP) is a well-known Traditional Chinese Medicine with anticancer
      activity. The aim of the present study was to investigate whether the aqueous
      extract of XHP (AEXHP) has anti-proliferative activity against the Hs578T TNBC
      cell line, and to elucidate its molecular mechanisms of action. First, an MTT
      assay was used to evaluate the anti-proliferative activity of AEXHP on the Hs578T
      cell line; furthermore, the cell cycle distribution, mitochondrial membrane
      potential and apoptotic rate were determined by flow cytometry, and western blot
      analysis was used to assess the expression of apoptosis and cell cycle regulatory
      proteins to investigate the mechanisms of action. The results revealed that the
      cell viability was significantly inhibited by AEXHP in a dose- and time-dependent
      manner. Apoptosis and mitochondrial membrane potential loss were detected, and
      after treatment with 4, 8 and 12 mg/ml AEXHP for 24 h, cleaved caspase-3 was 1.70
      , 1.81- and 1.84-fold of that of the control, while procaspase-3, procaspase-8,
      cleaved caspase-8, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)
      and the Bcl-2/Bax ratio were not significantly affected. Cell cycle analysis
      revealed that treatment with AEXHP led to S-phase arrest of Hs578T cells.
      Furthermore, AEXHP treatment resulted in decreased expression of cyclin A and
      cyclin dependent kinase 2 (CDK2), and increased expression of cyclin E and
      p21Cip1, as compared to the control group. In conclusion, the viability of Hs578T
      cells was significantly inhibited by AEXHP in a dose- and time-dependent manner,
      the likely mechanisms of which being induction of apoptosis, probably via the
      intrinsic, Bcl-2-independent pathway, and cell cycle arrest in S phase due to
      decreased expression of cyclin A and CDK2, and increased expression of cyclin E
      and p21Cip1.

PMID- 27882218
TI  - Adenovirus co-expressing CD40 ligand and interleukin (IL)-2 contributes to
      maturation of dendritic cells and production of IL-12.
AB  - The aim of the present study was to construct a chimeric adenovirus (Ad)5/F35 co
      expressing human CD4O ligand (CD4OL) and interleukin (IL)-2 (Ad5/F35 CD40L-IL-2).
      The infection efficiency to human monocyte-derived dendritic cells (Mo-DCs),
      expression of genes, phenotype changes and IL-12 production of Mo-DC by Ad5/F35
      CD40L-IL-2 were investigated. CD40L and IL-2 from total RNA extracted from human
      peripheral blood mononuclear cells (PBMCs) were cloned by reverse transcription
      polymerase chain reaction and used to construct Ad5/F35 CD40L-IL-2. The infection
      efficiency, expression of CD40L, and phenotype changes of Mo-DC infected with
      Ad5/F35 CD40L-IL-2 were analyzed using flow cytometry. The quantities of IL-2 and
      IL-12 in the supernatants of Mo-DC following infection of Ad5/F35 CD40L-IL-2 were
      measured by enzyme-linked immunosorbent assay. The CD40L and IL-2 genes were
      successfully cloned and the Ad5/F35 CD40L-IL-2 was constructed. Ad5/F35 CD40L-IL
      2 efficiently infected Mo-DCs with an infection efficiency of >75%, and the
      infected Mo-DCs expressed CD40L and secreted IL-2. The expression levels of
      cluster of differentiation (CD)80, CD86, CD40, and human leukocyte antigen
      antigen D related on Mo-DC were moderate; however, CD83 was low prior to
      infection of Ad5/F35 CD40L-IL-2. Those molecules, particularly CD83, were
      markedly upregulated 24 h after the infection. Increasing quantities of IL-12 in
      the supernatants were detected subsequent to infection at different time points
      in a time-dependent manner. Thus, Ad5/F35 CD40L-IL-2 efficiently infected human
      Mo-DCs and its products, CD40L and IL-2, were subsequently expressed. In
      addition, infection with Ad5/F35 CD40L-IL-2 stimulated the maturation of Mo-DC
      and high levels of IL-12 production.

PMID- 27882219
TI  - CYP2D6 gene polymorphisms in Brazilian patients with breast cancer treated with
      adjuvant tamoxifen and its association with disease recurrence.
AB  - At present, there is controversy regarding the efficacy of tamoxifen in breast
      cancer patients who are carriers of cytochrome P450 2D6 (CYP2D6) gene
      polymorphisms, in terms of recurrence and overall survival. Thus, the aim of the
      present study was to investigate the association of the CYP2D6 *4, *10 and *17
      gene polymorphisms with breast cancer recurrence in a Brazilian population. The
      cohort comprised 40 receptor-positive breast cancer patients without recurrence
      and 40 with distant recurrence. A 3-ml sample of peripheral blood was collected
      from each patient to determine the presence of the *4, *10 and *17 single
      nucleotide polymorphisms of the CYP2D6 gene by quantitative polymerase chain
      reaction analysis. There was no statistically significant difference between the
      two groups regarding the polymorphism frequency (P=0.246). The results revealed
      that intermediate metabolizers occurred in 5% of patients without recurrence and
      in 15% of those with distant recurrence. Poor metabolizers occurred in only 1
      patient (2.5%) per group, and there was no significant difference between the
      groups (P=0.789). The present study concluded that the CYP2D6 gene polymorphism
      in women with hormone-sensitive breast cancer treated with tamoxifen was not
      associated with disease recurrence.

PMID- 27882221
TI  - Overexpression of suppressor of IKBKE 1 is associated with vincristine resistance
      in colon cancer cells.
AB  - In a previous study, the suppressor of IKBKE 1 expression level was confirmed to
      be higher in vincristine (VCR)-resistant HCT-8 (HCT-8/V) colon cancer cells than
      in non-VCR-resistant HCT-8 cells. In the current study, IKBKE 1 expression in VCR
      resistant colon cancer cells was investigated further. HCT-8 and HCT-8/V human
      colon cancer cells were used, and polymerase chain reaction (PCR) primers were
      designed to amplify the IKBKE 1 gene. Fluorescence reverse transcription
      quantitative PCR (RT-qPCR) was performed to detect differences in IKBKE 1
      expression between sensitive and drug-resistant colon cancer cell lines. Western
      blotting was performed to further observe IKBKE 1 expression. Based on the RT
      qPCR and western blot results, IKBKE 1 expression was observed to be markedly
      higher in the HCT-8/V cells, and this difference was significant (P<0.05). Thus,
      IKBKE 1 expression was identified to be associated with the resistance of colon
      cancer cells to VCR.

PMID- 27882220
TI  - Effects of blueberries on migration, invasion, proliferation, the cell cycle and
      apoptosis in hepatocellular carcinoma cells.
AB  - The aim of the present study was to investigate the effects of blueberry
      consumption on the migration, invasion, proliferation, cell cycle and apoptosis
      in human hepatocellular carcinoma (HCC) cells, in order to provide clinical
      treatment and prevention strategies for liver cancer using anticancer therapeutic
      agents. Rabbiteye blueberry was prepared as fresh juice and fed to rats at low,
      moderate and high dosages (25, 50 and 100%, respectively) by daily gastric
      gavage. Seven days later, the rats were sacrificed and the blood serum was
      obtained for co-culture with HEPG2 cells. The MTT assay was used for detecting
      cell proliferation, Transwell assay was performed for migration and invasion
      evaluation, and cell cycle and apoptosis were assessed by flow cytometry. After
      co-culturing with the blood serum of rats that were fed different dosages of
      blueberry juice, the inhibition rate of HEPG2 cells in the three groups was
      significantly lower than that in the control group at 48 and 72 h (P<0.05). The
      number of migrated and transmembrane HEPG2 cells in the three groups was
      significantly lower than that in the control group at 48 and 72 h (P<0.05). The
      number of migrated HEPG2 cells in the high dosage group was significantly lower
      than that in the low dosage group at 48 h, and the numbers of migrated HEPG2
      cells in the high and moderate dosage groups were significantly lower than that
      in the low dosage group at 72 h (P<0.05). The number of transmembrane HEPG2 cells
      in the high dosage group was significantly lower than that in the low dosage
      group at 48 h (P<0.05). The numbers of HEPG2 cells at the G2/M stage in the three
      groups were significantly lower than that in the control group, and the number of
      HEPG2 cells in the high dosage group was significantly lower than that in the low
      dosage group, at 48 and 72 h (P<0.05). The apoptosis rate in the three groups was
      significantly higher than that in the control group, and the apoptosis rate in
      the high dosage group was significantly higher than that in the low dosage group
      at 48 and 72 h (P<0.05). Thus, blueberries may facilitate the clinical treatment
      of HCC, providing a novel therapeutic and prevention strategy for HCC as an
      anticancer therapeutic agent.

PMID- 27882222
TI  - Gastroprotective effects of arctigenin of Arctium lappa L. on a rat model of
      gastric ulcers.
AB  - In the present study, the gastroprotective effects of arctigenin of Fructus
      Arctii were evaluated and the possible underlying mechanisms of action were
      elucidated. Arctigenin (high-performance liquid chromatography purity, >99.0%)
      was isolated and purified from the seeds of Arctium lappa L. The anti-ulcerogenic
      activity of arctigenin against ulcers induced by absolute ethanol and acetic acid
      was evaluated in a Sprague-Dawley rat model. In addition, the antioxidant
      activity was assessed by measuring malondialdehyde (MDA) levels in an ethanol
      induced model and the anti-inflammatory effects were assessed by measuring five
      factors in an acetic acid-induced model. In the ethanol-induced model, arctigenin
      inhibited gastric lesions in a dose-dependent manner, by 53.04, 53.91 and 64.43%
      at doses of 0.05, 0.15 and 0.45 mg/kg, respectively. In addition, arctigenin
      reduced MDA (P<0.01) and increased superoxide dismutase (P<0.01) levels in serum
      when compared with the vehicle group. The lesion index induced by acetic acid was
      significantly inhibited by all doses of arctigenin (0.05, 0.15 and 0.45 mg/kg;
      P<0.01) in comparison to the vehicle group and in a dose-dependent manner. In
      addition, it was shown that the expression levels of tumor necrosis factor-alpha,
      interleukin-6 (IL-6), IL-10 and C-reactive protein were significantly decreased
      (P<0.05) in the arctigenin group compared with the vehicle group. Thus, the
      current study indicated that arctigenin exerted anti-ulcer activity, which may be
      associated with its reduction in oxidative and inflammatory damage. All the
      results indicate that arctigenin may be used as an effective therapeutic agent to
      prevent gastric ulcers.

PMID- 27882223
TI  - Hepatitis B patients exhibiting mild alanine aminotransferase elevation: A
      comparative analysis of treatment with and without Bicyclol tablets.
AB  - The aim of the present study was to analyze the medicinal effect of Bicyclol
      tablets on patients with chronic hepatitis B (CHB) and concomitant mild alanine
      aminotransferase (ALT) elevation (40-80 IU/l). A retrospective cohort study,
      which included patients from the hospital information system (HIS; established by
      the Chinese Academy of Medical Sciences) viral hepatitis database comprised of 18
      third-grade class A hospitals in China, was performed. Patients were divided into
      an exposed group (administered with Bicyclol tablets) and a non-exposed group (no
      administration of Bicyclol tablets). The CHB patients that exhibited mild ALT
      elevation provided the curative effect analysis data set, and the patients with
      viral hepatitis who underwent more than two creatinine/hemoglobin/leucocyte
      examinations served as the safety analysis data set. The factors influencing ALT
      normalization rate were analyzed and the safety of Bicyclol tablets was assessed.
      In total, 82 pairs of patients were included in the curative effect analysis, and
      single factor analysis revealed that the ALT normalization rate of the exposed
      group was statistically significantly higher than that of the non-exposed group
      (P=0.040) for patients with mild ALT elevation. After adjusting for patient age,
      gender, baseline ALT levels, state of illness upon admission, pattern of
      hospitalization, hospitalization days and drug combination, the odds ratio (95%
      confidence interval) of the ALT normalization rate of the exposed group was 2.156
      (1.103-4.215) when compared with the non-exposed group. During treatment, the
      occurrence rates of creatinine/hemoglobin/leucocyte level abnormalities of the
      exposed group, which were included in the safety analysis were statistically
      significantly lower than those of the non-exposed group (P<0.05). These findings
      indicate that Bicyclol tablets improve the ALT normalization rate of CHB patients
      exhibiting mild ALT elevation.

PMID- 27882224
TI  - Correlation between serum parathyroid hormone levels and coronary artery
      calcification in patients without renal failure.
AB  - The aim of the present study was to investigate the correlation between serum
      parathyroid hormone (PTH) levels and coronary artery calcification (CAC) in
      patients without renal failure, as well as to determine independent risk factors
      of CAC score (CACS). A total of 157 patients who underwent coronary computed
      tomography angiographic examination at the 101th Hospital of the People's
      Liberation Army between December 2013 and February 2015 were retrospectively
      evaluated. The correlation between PTH levels and CACS was determined using a
      Pearson correlation analysis. A receiver operating characteristic (ROC) curve was
      drawn to determine the best cutoff PTH level for prediction of CAC. The
      independent association between serum PTH levels and CAC was analyzed by using a
      logistic regression analysis model with the response variable Be binary class.
      The results revealed that PTH levels in patients in the CAC group were
      significantly higher than those of patients in the non-calcification group. PTH
      levels were positively correlated with CACS (r=0.288, P<0.001). The ROC curve
      suggested that a PTH level of >=31.05 pg/ml was the best cut-off point for the
      prediction of CAC, with a sensitivity of 80.88%, specificity of 60.67% and an
      area under the curve of 0.761. After including predictive factors for CAC
      (gender, age, smoking status, diabetes, hypertension, hyperlipidemia, body mass
      index, glomerular filtration rate and calcium, phosphorus, calcium-phosphorus
      product, magnesium, PTH, total cholesterol, low-density lipoprotein cholesterol,
      triglyceride, high-density lipoprotein cholesterol and C-reactive protein
      levels), the odds ratio of the serum PTH levels regarding the prediction of CAC
      was 1.050 (95% confidence interval, 1.027-1.074; P<0.001). In conclusion, the
      present study suggested that serum PTH levels are correlated with CAC in patients
      without renal failure and may thus be used as a reliable predictor of CAC.

PMID- 27882225
TI  - Carbonated soft drinks alter hepatic cytochrome P450 isoform expression in Wistar
      rats.
AB  - The aim of the current study was to examine the effects of chronic consumption of
      soft drinks (SDs) on hepatic oxidative stress and cytochrome P450 enzymes (CYPs)
      expression in the livers of Wistar rats. For 3 consecutive months, the rats had
      free access to three different soft drinks, Coca-Cola, Pepsi-Cola and 7-UP. The
      rats were subsequently compared with control group rats that had consumed water.
      Blood and hepatic tissue samples were assayed for the changes in antioxidants,
      liver function biomarkers and hepatic gene expression for different isoforms of
      hepatic CYP. The results indicated that SD consumption (SDC) decreased serum
      antioxidant levels and increased malondialdehyde secretion, and increased liver
      biomarkers (glutamate pyruvate transaminase and glutamate oxaloacetate). SD
      induced alterations in mRNA expression of hepatic antioxidants and cytochrome
      isoforms. The expression of peroxidase, catalase, CYP1A2, CYP3A2 and CYP2C11 in
      the liver were upregulated following SDC. By contrast, CYP2B1 was downregulated
      after 3 months of SDC in liver tissue samples. Thus, the present findings
      indicate that SDs induced oxidative stress in the liver of Wistar rats and for
      the first time, to the best of our knowledge, indicate that SDC disrupts hepatic
      CYP enzymes that may affect drug metabolism. Therefore, drug-dosing programs
      should be carefully designed to take these novel findings into consideration for
      the treatment of diseases.

PMID- 27882226
TI  - Effect of dehydration heat exposure on thoracic aorta reactivity in rats.
AB  - The aim of the present study was to investigate the effect of one week
      dehydration heat exposure on thoracic aorta reactivity in rats. Eighteen Male
      Sprague-Dawley rats were randomly divided into 3 groups (n=6 each group): Control
      group (CN), heat exposure group (HE), dehydration heat exposure group (DHE). The
      CN group was exposed to a room temperature of 24 degrees C, while the HE and DHE
      groups were exposed to a heat temperature of 32 degrees C. After 7 days of heat
      exposure, the heart rate and blood pressure of the rats were measured, and the
      noradrenaline (NA)-induced contraction on the aorta rings was measured by tension
      recording. The average contents of malondialdehyde (MDA) and superoxide dismutase
      (SOD) in serum were detected using ELISA. The expression of apoptotic genes in
      the thoracic aorta was measured using RT-PCR. Compared with CN, the heart rate in
      the HE and DHE groups had a tendency to become retarded, but there was no
      significant difference (P>0.05). In the HE group, the systolic blood pressure
      (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) of the
      rats were significantly higher than that of the CN (P<0.05). In the DHE group,
      the SBP of rats was significantly higher than that of the CN (P<0.05), while the
      SBP, DBP, and MAP of the rats were decreased compared to the rats in the HE
      group, although there was no statistical significance (P>0.05). In the HE and DHE
      groups, the NA-induced contraction on the rats thoracic aorta ring was larger
      than that of the CN (P<0.05), albeit there was no significant difference between
      the HE and DHE groups (P>0.05). The serum SOD content decreased in the HE and DHE
      groups, however, the reduction was significant only in the DHE group (P<0.05).
      The content of MDA in serum was significantly increased in the DHE group
      (P<0.05). The expression of BAX was significantly upregulated whereas Bcl2
      expression was decreased in the DHE group (P<0.05). The results showed that a
      high temperature was harmful to the body, especially in the case of lack of food
      and water. Additionally, the heat exposure elevated blood pressure, and increased
      arterial reactivity, which were related to the elevated production of MDA, led to
      the impaired production of SOD, and an increase of cell apoptosis. These findings
      are useful to understand the influence of dehydrated heat exposure on the
      vascular function, and they provide certain theoretical and experimental guidance
      for protection under high temperature.

PMID- 27882227
TI  - G2691A and C2491T mutations of factor V gene and pre-disposition to myocardial
      infarction in Morocco.
AB  - Coagulation factor Leiden mutation has been described as a common genetic risk
      factor for venous thrombosis; however, this mutation was reported to be
      practically absent in an African population. Recently, a novel non-sense mutation
      in the gene encoding factor V has been associated with the risk of occurrence of
      cardio-cerebrovascular diseases such as stroke and venous thrombosis. The aim of
      the present study was to investigate whether the factor V Leiden (FVL) and C2491T
      non-sense mutations are associated with the risk of developing myocardial
      infarction. Genotyping of FVL and C2491T FV was performed using the polymerase
      chain reaction restriction fragment length polymorphism method on a sample of 100
      patients with myocardial infarction as well as 211 controls. In the study
      population, the frequency of the FVL mutation was practically zero. However, with
      regard to the C2491T mutation, the TT genotype was associated with an increased
      risk of myocardial infarction [odds ratio (OR)=3.16, 95% confidence interval
      (CI): 1.29-7.71, P=0.03]. A significant association between the C2491T FV
      mutation and the risk of myocardial infarction was identified using recessive
      (OR=2.74, 95% CI: 1.14-6.58, P=0.04), dominant (OR=1.85, 95% CI: 1.13-3.04,
      P=0.02) and additive (OR=1.88, 95% CI: 1.25-2.80, P=0.004) models. Furthermore, a
      positive correlation was found between the presence of the C2491T FV mutation and
      hypertension (P=0.02), which is associated with myocardial infarction. In
      conclusion, the results of the present study suggested that the C2491T non-sense
      mutation of the FV gene may be a risk factor for myocardial infarction in a
      Moroccan population.

PMID- 27882228
TI  - Oxymatrine inhibits microglia activation via HSP60-TLR4 signaling.
AB  - Oxymatrine (OMT) is an alkaloid extracted from Sophora flavescens, which has
      broad anti-inflammatory, antitumor and immunosuppressant actions. However, the
      underlying molecular mechanisms have remained elusive. Heat shock protein 60
      (HSP60) has recently been shown to have an important role in autoimmune
      reactions. The present study aimed to investigate whether OMT exerts its anti
      inflammatory effects by inhibiting microglial activation and examined the role of
      HSP60 in this process. Western blot analysis and ELISA showed that OMT decreased
      the expression and release of HSP60 by LPS-activated BV2 cells. The expression of
      heat shock factor 1, the transcription factor of HSP60, was also suppressed by
      OMT. Extracellular HSP60 has been previously indicated to induce microglial
      apoptosis through the Toll-like receptor (TLR)-4 pathway. Flow cytometric
      analysis demonstrated that LPS treatment induced apoptosis of BV2 cells, which
      was inhibited by OMT in parallel with inhibition of LPS-induced expression of TLR
      4. Furthermore, OMT was shown to suppress the levels of myeloid differentiation
      factor (MYD)88, nuclear factor (NF)-kappaB, caspase-3, inducible nitric oxide
      synthase, tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6. In light
      of these results, it was concluded that OMT may exert its neuroprotective effects
      via HSP60/TLR-4/MYD88/NF-kappaB signaling pathways to inhibit microglial
      activation. OMT may therefore offer substantial therapeutic potential for
      treating neurodegenerative diseases associated with microglial activation.

PMID- 27882229
TI  - Risk factors for osteoporosis in patients with end-stage liver disease.
AB  - Patients with end-stage liver disease (ESLD) were evaluated and their clinical
      features were compared with the aim of identifying risk factors for osteoporosis.
      Seventy-nine patients with ESLD were enrolled in the current study. Bone mineral
      density (BMD) was assessed by dual-energy X-ray absorptiometry and compared with
      clinical features in patients with ESLD. BMD was identified to be significantly
      correlated with body mass index (r=0.430; P=0.001) and inversely correlated with
      total bile acid (r=-0.228; P=0.049) and urine N-telopeptide type I
      collagen/creatinine ratio (r=-0.280; P=0.024). Patients with osteoporosis were
      significantly older (osteoporosis vs. no osteoporosis, 63.0 vs. 56.0 years;
      P<0.05) and had higher values for total bile acid (osteoporosis vs. no
      osteoporosis, 306.0 vs. 129.1 umol/l; P<0.05) and corrected calcium [osteoporosis
      vs. no osteoporosis, 9.85 (8.7-10.7) vs. 9.70 (8.8-10.6) mg/dl; P<0.05]. In
      multivariate analysis, age (beta=-0.015+/-0.06; P=0.009) and total bile acid
      (beta=-0.001+/-0.0001; P=0.041) were identified as independent factors for
      osteoporosis. Finally, the risk score for osteoporosis was defined as follows:
      Risk score=1.78-0.001 * total bile acid-(0.16 * age). The area under the receiver
      operating characteristic (ROC) curve risk score for osteoporosis is 0.778. Thus,
      the risk scores calculated in the present study may be used to predict
      osteoporosis in patients with ESLD.

PMID- 27882230
TI  - Evaluation of interferon-induced transmembrane protein-3 (IFITM3) rs7478728 and
      rs3888188 polymorphisms and the risk of pulmonary tuberculosis.
AB  - The current study aimed to examine the possible association between the
      interferon-induced transmembrane protein-3 (IFITM3) gene polymorphisms and risk
      of pulmonary tuberculosis (PTB) in a sample population. This case-control study
      was conducted on 188 PTB patients and 169 healthy subjects. The rs7478728 and
      rs3888188 variants of IFITM3 were genotyped using polymerase chain reaction
      restriction fragment length polymorphism. The findings showed no significant
      association between rs7478728 polymorphism and risk of PTB. Regarding rs3888188
      polymorphism, the TG genotype as well as G allele significantly increased the
      risk of PTB [odds ratio (OR)=2.48, 95% confidence interval (CI): 1.42-4.53;
      P=0.002, and OR=2.26, 95% CI: 1.33-3.86; P=0.003, respectively]. In conclusion,
      the findings revealed that rs3888188 polymorphism increased the risk of PTB in a
      sample of Iranian population. Additional investigation with larger sample sizes
      and different ethnicities are needed to verify our findings.

PMID- 27882231
TI  - Organic cation transporter 6 directly confers resistance to anticancer platinum
      drugs.
AB  - Organic cation transporters (OCTs) of the solute carrier family 22 have a
      critical role in the cellular uptake of anticancer platinum drugs. Recently, we
      found that a decreased OCT6 expression is associated with a reduced intracellular
      uptake of cisplatin (CDDP), and concomitant resistance to CDDP. In the present
      study, we examined whether OCTs directly confer resistance to another platinum
      drug, oxaliplatin (L-OHP). To address this, we used parental lung cancer cell
      lines, PC-14 and SBC3; L-OHP-resistant sublines, PC-14/L-OHP and SBC3/L-OHP; and
      one CDDP-resistant subline PC-14/CDDP, to examine the relationships between the
      expression of OCTs and intracellular platinum drug concentration or platinum drug
      resistance. The two L-OHP-resistant sublines showed cross resistance to CDDP and
      L-OHP, and a decreased expression of OCT6. The intracellular accumulation of L
      OHP in PC-14/L-OHP cells was reduced compared with the parental cells. The
      findings suggested that a reduced OCT6 expression confers platinum drug
      resistance in the sublines by decreasing the uptake of platinum drugs. Using the
      PC-14/CDDP cell line engineered to overexpress OCT6, we confirmed that the
      intracellular L-OHP concentration was increased concomitantly with OCT6
      overexpression compared with the parental cell line. Additionally, OCT6 was
      expressed in a screening panel of lung and colon cancer tissues and matched
      normal control tissues. Taken together with the previous results, the present
      findings indicate that OCT6 is directly involved in platinum drug resistance by
      mediating platinum drug uptake in cancer cells.

PMID- 27882233
TI  - High-dose rate brachytherapy for local recurrent adenoid cystic carcinoma of the
      tongue base following postoperative external beam radiotherapy.
AB  - Adenoid cystic carcinoma is a rare neoplasm commonly originating from the minor
      salivary glands. The clinical findings typical of this tumor include slow growth,
      perineural invasion and high frequency of local recurrence. In this study, a
      patient presented with a tongue base lesion that was treated with surgical
      excision and additional postoperative external beam radiotherapy. However, local
      recurrence occurred 8 months after radiotherapy. If recurrence occurs after
      radiation therapy, total glossectomy should be considered. However, the patient
      refused re-operation and, considering the patient's age, brachytherapy was used
      to ensure organ preservation. Complete remission was achieved following
      brachytherapy, without serious side effects. There has been no progression of the
      lesion during a follow-up period of 2 years.

PMID- 27882232
TI  - Metastatic gastric cancer to the female genital tract.
AB  - Metastases to the female genital tract from gastric cancer are rare, but they
      significantly worsen the prognosis of such patients. The potential routes for
      metastasis to the female genital tract from gastric cancer include hematogenous
      spread, lymphatic spread and surface implantation. The rate of lymphatic
      metastasis to the ovary from gastric cancer has been reported to be higher
      compared with that from colorectal cancer. Uterine or Fallopian tube metastases
      are usually secondary to ovarian metastases, which are typically identified prior
      to the detection of gastric cancer in half of all synchronous cases, with
      complaints of abdominal distention, pain, palpable mass, or abnormal uterine
      bleeding. The prognosis of patients with female genital tract metastases from
      gastric cancer is extremely poor, and is worse compared with that of other
      primary sites, such as the breast and colorectum. In the past, surgical
      intervention in such patients consisted mainly of palliative resection to relieve
      the symptoms associated with a sizeable pelvic mass. However, recent
      retrospective studies based on a relatively small number of patients have
      reported that surgical tumor debulking plus chemotherapy may improve the
      prognosis of patients with metastatic ovarian cancer originating from gastric
      cancer.

PMID- 27882234
TI  - Dysgerminoma developing from an ectopic ovary in a patient with WAGR syndrome: A
      case report.
AB  - WAGR syndrome is caused by an 11p13 deletion and includes Wilms' tumor, aniridia,
      genitourinary anomalies and mental retardation. We encountered a case of a
      dysgerminoma originating in an ectopic ovary in a woman with WAGR syndrome. Our
      patient was a 24-year-old nulliparous woman who was diagnosed with WAGR syndrome.
      The patient had undergone left nephrectomy for a Wilms' tumor and postoperative
      chemotherapy at the age of 7 months. She also had a history of glaucoma surgery
      in both eyes, and was followed up at the Department of Pediatrics for diabetes
      mellitus, hypertension, liver dysfunction and hyperuricemia. The patient was
      investigated for oliguria and had elevated levels of blood urea nitrogen (45
      mg/dl) and creatinine (5.4 mg/dl); she was admitted to the hospital with acute
      renal failure and a computed tomography scan revealed a pelvic tumor with a long
      axis of 10 cm that was obstructing the right ureter. Following insertion of a
      ureteral stent, the tumor was removed. The tumor had developed in the
      retroperitoneal space independent of the ovaries. The right adnexa were normal.
      The tumor was histopathologically diagnosed as dysgerminoma. Follicles were found
      in part of the tumor; it was thus hypothesized that the tumor developed from an
      ectopic ovary. The patient was administered etoposide after surgery, and has been
      recurrence-free for 4 years since treatment.

PMID- 27882235
TI  - Intraoperative molecular analysis of sentinel lymph nodes following neoadjuvant
      chemotherapy in patients with clinical node negative breast cancer: An
      institutional study.
AB  - Sentinel lymph node biopsy (SLNB) is an accurate, safe method for determining the
      axillary lymph node status. However, insufficient evidence exists to support the
      recommendation of SLNB in patients who have had neoadjuvant chemotherapy (NAC) to
      downsize tumours and allow for breast conservation surgery. The present study
      aimed to use molecular approaches to evaluate the feasibility and accuracy of
      SLNB in patients treated with NAC prior to SLN mapping and surgery. A total of 50
      consecutive patients with operable invasive breast carcinomas who had received
      prior NAC were assessed using the one-step nucleic acid amplification (OSNA)
      method. The rate of SLN identification was 100%. The OSNA assay showed that 29
      patients (58%) were negative for SLN and 21 patients (42%) were positive. In 19
      of these 21 patients (90.48%), the SLN was the only positive lymph node. No
      axillary lymph nodes metastases were observed in patients with isolated tumour
      cells or with micrometastases. The OSNA assay is a highly sensitive, specific and
      reproducible diagnostic technique that can be used to analyse SLNs following NAC.
      The total tumoral load may assist with predicting additional non-SLN metastases.

PMID- 27882236
TI  - Improved survival with double platinum therapy transcatheter arterial infusion
      using cisplatin and transcatheter arterial chemoembolization using miriplatin for
      BCLC-B hepatocellular carcinoma.
AB  - Transcatheter arterial chemoembolization (TACE) is the standard therapy for
      Barcelona Clinic Liver Cancer (BCLC) classification intermediate stage B
      hepatocellular carcinoma (HCC). However, other transcatheter methods, such as
      transcatheter arterial infusion (TAI), also play an important role in the
      treatment of advanced HCC. Although it has been reported that TAI with a high
      concentration of a fine-powder formulation of cisplatin (DDP-H) reduced
      intrahepatic recurrence and improved survival, the combined use of TAI with DDP-H
      and TACE has not yet been investigated. The aim of this study was to evaluate
      which TACE chemotherapeutic agent in combination with DDP-H TAI contributes more
      to improved survival in BCLC-B HCC. Survival was analyzed in 55 patients who
      underwent DDP-H TAI and TACE for BCLC-B HCC. The patients were classified into
      two groups; Epirubicin was used as the TACE agent in 29 patients, whereas
      miriplatin was used in 26 patients. The cumulative survival rates at 1 and 2
      years were 66.4 and 36.0% in the epirubicin and 95.8 and 61.30% in the miriplatin
      group, respectively. Survival time was significantly prolonged in the miriplatin
      group compared with that in the epirubicin group. Multivariate analysis
      identified Child-Pugh classification and up-to-seven criteria as factors
      affecting survival. In addition, the selection of miriplatin as the TACE
      chemoagent was the treatment factor that most significantly affected survival.
      Thus, double-platinum therapy with DDP-H TAI and miriplatin TACE may be a useful
      treatment strategy for improving survival in BCLC-B HCC patients.

PMID- 27882237
TI  - Autologous tumor immunizing devascularization of an invasive colorectal cancer: A
      case report and literature review.
AB  - Colorectal cancer is the third most common cancer. Approximately 20% of patients
      have at the time of presentation metastasized colorectal cancer, which is
      incurable in ~80% of cases. The present case report describes a typical case
      diagnosed with an advanced invasive colorectal adenocarcinoma, with two suspect
      hypodense lesions in the liver, as revealed by sonography. Judged inoperable for
      a curative outcome by radical resection, the patient was treated with a novel
      surgical technique based on stimulating the immune system, termed 'autologous
      tumor immunizing devascularization' (ATID). The tumor was isolated from its
      surroundings by ligature of arteries and veins, and subsequently the completely
      devascularized tumor was left in situ. The distal part of the rectum was closed,
      and a stoma was made from the proximal part of the colon. Following ATID, the
      stressing pathophysiological condition of the completely isolated tumor provoked
      a generalized cellular immune response, which led to the elimination of the
      devascularized tumor and distant lesions without causing sepsis. The patient did
      not experience any serious side-effects following the operation, and refused any
      adjuvant chemo- and/or radiotherapy. To date, the patient has no complaints and
      remains in good health after the ATID intervention, already more than 14 years.
      The present case study provides a typical demonstration of the clinical safety of
      ATID, and also indicates both the immunizing and the curative potential of the
      method.

PMID- 27882238
TI  - Large uterine pyomyoma in a perimenopausal female: A case report and review of 50
      reported cases in the literature.
AB  - Pyomyoma is a rare complication, which withoug antibiotics or surgical
      intervention, may cause sepsis and mortality. The present study reported a case
      of large uterine pyomyoma in a perimenopausal female. A 53-year-old multigravida
      woman was referred to the Department of Obstetrics and Gynecology (Wakayama
      Medical University, Wakayama, Japan) due to progressive abdominal distension. The
      patient presented with anemia gravis, severe inflammatory reaction and cachexia.
      Computed tomography revealed a large unilocular mass, 50 cm in size, with an
      irregular surface and thickened wall, occupying the entire abdomen. Following
      antibiotic medication, the patient underwent a total abdominal hysterectomy and
      bilateral salpingo-oophorectomy. Intraoperative findings demonstrated a solid
      tumor arising from the back of the uterine body. A total of 12 liters of
      purulent, malodorous fluid was drained from the tumor. The resected mass was 50
      cm in size and 13.5 kg in weight. Cultures of the pus revealed the presence of
      Streptococcus agalactiae. Pathological findings revealed suppurative leiomyoma
      with no malignancy. Large pyomyoma is difficult to distinguish from a
      gynecological malignant tumor types, particularly in perimenopausal women with
      non-specific clinical presentation. Although pyomyoma is a benign tumor, care
      must be taken to discriminate these from large abdominal tumors.

PMID- 27882239
TI  - Desmoplastic fibroma of the distal tibia: A case report of a minimally invasive
      histological diagnosis.
AB  - Desmoplastic fibroma (DF) is a benign, rare fibroblastic intraosseous neoplasm
      histologically resembling a desmoid soft tissue tumor. Although classified as
      benign, DF frequently exhibits an aggressive behavior, has a moderate-to-high
      recurrence rate, and often causes pathological fractures and extensive bone
      destruction. This case report presents an incidentally detected DF of the tibia,
      which was diagnosed using a minimally invasive approach. A 36-year-old African
      female patient was referred to the Department of Diagnostic Imaging of
      Arcispedale Santa Maria Nuova-IRCCS (Reggio Emilia, Italy), to be examined by a
      computed tomography scan on an outpatient basis, after an x-ray examination of
      the tibia, which was performed after an injury to exclude the presence of a
      fracture, revealed a hyperlucency of unknown origin. The aim of this study was to
      discuss the clinical, histological, immunohistochemical and radiographic
      characteristics of this rare neoplasm, with a focus on image-guided bone biopsy.

PMID- 27882240
TI  - T2-based temperature monitoring in bone marrow for MR-guided focused ultrasound.
AB  - BACKGROUND: Current clinical protocols for MR-guided focused ultrasound (MRgFUS)
      treatment of osseous lesions, including painful bone metastases and osteoid
      osteomas, rely on measurement of the temperature change in adjacent muscle to
      estimate the temperature of the bone. The goal of this study was to determine if
      T2-based thermometry could be used to monitor the temperature change in bone
      marrow during focused ultrasound ablation of bone lesions. METHODS: We
      investigated the dependence of T2 on temperature in ex vivo bovine yellow bone
      marrow at 3T and studied the influence of acquisition parameters on the T2
      measurements. We examined if T2 changes in red bone marrow caused by the ablation
      of ex vivo trabecular bone were reversible and measured the patterns of heating
      and tissue damage. The technique was validated during the ablation of intact ex
      vivo bone samples and an in vivo animal model. RESULTS: Results of the
      calibration experiment showed a linear relationship (7 ms/ degrees C) between T2
      change and temperature and could be used to quantify the temperature during
      heating of up to 60  degrees C. During trabecular bone ablation, we observed a
      linear relationship (5.7 ms per  degrees C) between T2 and temperature during the
      heating stage of the experiment. After cool down, there was residual T2 elevation
      (~35 ms) in the ablated area suggesting irreversible tissue changes. In ex vivo
      and in vivo cortical bone ablation experiments, we observed an increase in T2
      values in the marrow adjacent to the intersection of the cortical bone and the
      beam path. The in vivo experiment showed excellent correspondence between the
      area of T2 elevation in marrow during the ablation and the resulting non
      enhancing area in the post-contrast images. CONCLUSIONS: In this study, we have
      demonstrated that T2-based thermometry can be used in vivo to measure the heating
      in the marrow during bone ablation. The ability to monitor the temperature within
      the bone marrow allowed more complete visualization of the heat distribution into
      the bone, which is important for local lesion control.

PMID- 27882241
TI  - Immune Profile of Honduran Schoolchildren with Intestinal Parasites: The Skewed
      Response against Geohelminths.
AB  - Soil-transmitted helminth infections typically induce a type-2 immune response
      (Th2), but no immunoepidemiological studies have been undertaken in Honduras, an
      endemic country where the main control strategy is children's annual deworming.
      We aimed to characterize the immune profile of Honduran schoolchildren harbouring
      these parasitoses. Demographic and epidemiological data were obtained through a
      survey; nutritional status was assessed through anthropometry; intestinal
      parasites were diagnosed by formol-ether and Kato-Katz; and blood samples were
      collected to determine immunological markers including Th1/Th2 cytokines, IgE,
      and eosinophil levels. A total of 225 children participated in the study, all of
      whom had received deworming during the national campaign five months prior to the
      study. Trichuriasis and ascariasis prevalence were 22.2% and 20.4%, respectively.
      Stunting was associated with both age and trichuriasis, whereas ascariasis was
      associated with sex and household conditions. Helminth infections were strongly
      associated with eosinophilia and hyper-IgE as well as with a Th2-polarized
      response (increased levels of IL-13, IL-10, and IL4/IFN-gamma ratios and
      decreased levels of IFN-gamma). Pathogenic protozoa infections were associated
      with a Th1 response characterized by elevated levels of IFN-gamma and decreased
      IL10/IFN-gamma ratios. Even at low prevalence levels, STH infections affect
      children's nutrition and play a polarizing role in their immune system.

PMID- 27882242
TI  - Development of a Loop Mediated Isothermal Amplification for Diagnosis of Ascaris
      lumbricoides in Fecal Samples.
AB  - Ascaris lumbricoides is a nematode parasite that causes the common tropical
      infection ascariasis in humans. It is also considered among the neglected
      tropical diseases. Diagnosis relies mainly on microscopy-based methods which are
      laborious, are limited by low sensitivity, and require high expertise. We have
      developed a loop mediated isothermal amplification (LAMP) for diagnosis of
      ascariasis in fecal samples, based on the first internal transcribed (ITS-1)
      spacer region of the ribosomal DNA. We used Primer Explorer V4 software to design
      primers. Ascaris adult and ova were obtained from naturally infected school
      children, whose parents/guardians gave consent for their participation in the
      study. Genomic DNA was extracted using alkaline lysis method and amplified by
      LAMP at 63 degrees C for 45 minutes. LAMP products were visualized by naked eyes
      after adding SYBR Green dye and also on agarose gel. LAMP successfully and
      reliably detected Ascaris DNA from a single egg and in fecal samples. The assay
      specifically detected Ascaris DNA without amplifying DNA from ova of other
      parasites which commonly coexist with A. lumbricoides in feces. The developed
      LAMP assay has great potential for use in ascariasis diagnosis at the point of
      care and in low infection intensity situation that characterize control and
      elimination campaigns.

PMID- 27882243
TI  - Glaukos iStent inject(r) Trabecular Micro-Bypass Implantation Associated with
      Cataract Surgery in Patients with Coexisting Cataract and Open-Angle Glaucoma or
      Ocular Hypertension: A Long-Term Study.
AB  - Purpose. To evaluate the long-term efficacy and safety of the iStent inject
      device (Glaukos Corporation, Laguna Hills, CA) combined with phacoemulsification
      in patients with coexistent cataract and open-angle glaucoma or ocular
      hypertension (OHT). Methods. A prospective, uncontrolled, nonrandomized,
      interventional case series study was conducted in patients with both mild or
      moderate open-angle glaucoma or OHT and cataract. Patients underwent cataract
      surgery along with the implant of two iStent inject devices. Outcome measures
      were intraocular pressure (IOP), topical hypotensive medications required, and
      best-corrected visual acuity (BCVA). Results. 20 patients were enrolled. Mean
      follow-up was 47.4 +/- 18.46 months. Mean baseline IOP was 19.95 +/- 3.71 mmHg
      with medication and 26 +/- 3.11 mmHg after washout. Mean end-follow-up IOP was
      16.25 +/- 1.99 mmHg, representing an IOP decrease of 36.92%, 9.74 +/- 3.14 mmHg
      (P < 0.001), from baseline washout IOP. The mean number of medications was
      significantly reduced from 1.3 +/- 0.66 to 0.75 +/- 0.79 (P = 0.017). 45% of
      patients were medication-free by the end of follow-up. Mean log?MAR BCVA improved
      significantly from 0.42 +/- 0.16 to 0.18 +/- 0.16 (P < 0.001). No complications
      of surgery were observed. Conclusion. The iStent inject device combined with
      cataract surgery served to significantly reduce both IOP and medication use in
      the long term in patients with coexistent open-angle glaucoma or ocular
      hypertension (OHT) and cataract.

PMID- 27882244
TI  - Evaluation of Peripapillary Nerve Fiber Layer after Dexamethasone Implantation
      (Ozurdex) in Branch Retinal Vein Occlusions.
AB  - Purpose. To evaluate the peripapillary retinal nerve fiber layer (RNFL)
      thicknesses of patients treated with intravitreal Ozurdex implant due to branch
      retinal vein occlusion (BRVO) related macular edema (ME). Methods. Thirty-three
      eyes of 33 patients treated with Ozurdex implant due to ME associated with BRVO
      were included in the study. Ophthalmic examinations including determination of
      best corrected visual acuity (BCVA), measurement of intraocular pressure (IOP),
      and central macular thickness (CMT) and peripapillary RNFL assessment with
      optical coherence tomography (OCT) were performed before the injection of Ozurdex
      implant and during the 6-month follow-up period after the injection. Results. The
      mean age was 55.2 +/- 7.4 (range: 40-68) years. The BCVAs were significantly
      increased and CMTs were significantly decreased at month 3 and month 6 visits
      compared to baseline values. The mean IOP was significantly increased from
      baseline at day 1, week 1, and month 1 visits (p1 = 0.008, p2 = 0.018, and p3 =
      0.022, resp.). The average and inferior quadrant peripapillary RNFL thicknesses
      were significantly reduced at month 6 control visit compared to baseline values
      (both p < 0.001). Conclusions. Ozurdex implant improved the BCVA and reduced the
      CMT in the eyes with RVO related ME. However, IOP elevations occurred within the
      first month after the injection and the average and inferior quadrant RNFL
      thinning was found six months after the injection. Further controlled studies are
      warranted.

PMID- 27882245
TI  - Ocular Biocompatibility of Poly-N-Isopropylacrylamide (pNIPAM).
AB  - Purpose. To study the safety of intravitreal injections of poly-N
      isopropylacrylamide (pNIPAM) tissue adhesive in rabbit eyes. Methods. Twelve
      study rabbits received an intravitreal injection of 0.1 mL 50% pNIPAM in the
      right eye. Follow-up examinations included color fundus photography, fundus
      fluorescein angiography (FA), optical coherence tomography (OCT), and
      electroretinography (ERG). Subsequent to the last follow-up assessment, the
      rabbits were sacrificed and histopathological study on the scleral incision sites
      was performed. Results. All study animals developed mild to moderate levels of
      inflammatory reaction in the conjunctiva, anterior chamber, and the anterior
      vitreous during the first month of follow-up. After this period, the level of the
      inflammatory reaction progressively decreased and completely disappeared after
      the third month of follow-up. The lens and cornea remained clear during the
      entire follow-up period. OCT and FA did not show areas of retinal damage or
      neovascularization. Histological and ERG studies of eyes injected with pNIPAM
      demonstrated absence of retinal toxicity. Conclusion. Intravitreal injections of
      pNIPAM were nontoxic in this animal study, and pNIPAM may be safe to be used as a
      bioadhesive in certain retinal diseases.

PMID- 27882246
TI  - The Impact of Perceived Stress and Coping Adequacy on the Health of Nurses: A
      Pilot Investigation.
AB  - Stress and coping abilities influence the health and work performance of nurses.
      However, little is known about the combined influence of stress perception and
      perceived coping adequacy and its impact on the health of nurses. This study
      examined the relationship between stress, coping, and the combined influences of
      perceived stress and coping abilities on health and work performance. A valid and
      reliable questionnaire was completed by 120 nurses in a Midwestern hospital in
      the USA. In general, the nurses were not healthy: 92% had moderate-to-very high
      stress levels; 78% slept less than 8 hours of sleep per night; 69% did not
      exercise regularly; 63% consumed less than 5 servings of fruits and vegetables
      per day; and 22% were classified as binge drinkers. When confronted with
      workplace stress, 70% of nurses reported that they consumed more junk food and
      63% reported that they consumed more food than usual as a way of coping. Nurses
      in the "high stress/poor coping" group had the poorest health outcomes and
      highest health risk behaviors compared to those in other groups. The combined
      variables of perceived stress and perceived coping adequacy influenced the health
      of nurses. Therefore, worksite health promotion programs for nurses should focus
      equally on stress reduction, stress management, and the development of healthy
      coping skills.

PMID- 27882248
TI  - Successful Interventional Management for Pulmonary Arterial Injury Secondary to
      Pacemaker Implantation.
AB  - Subclavian vein puncture is a relatively fast and safe technique to access the
      right heart for placement of pacemaker leads. Hemothorax related to injury of the
      pulmonary artery (PA) is a rare complication of subclavian vein access but can be
      life-threatening. We report a case of hemothorax occurring after subclavian vein
      puncture for pacemaker implantation. No cases of transcatheter arterial
      embolization for PA injury secondary to pacemaker implantation have been
      reported. Understanding of this rare complication after pacemaker implantation
      along with its specific clinical presentation may lead to early diagnosis and
      intervention.

PMID- 27882247
TI  - Living on the Edge: Social Exclusion and the Receipt of Informal Care in Older
      People.
AB  - Older people have been identified as being at risk of social exclusion. However,
      despite the fact that care is commonly required in later life and the majority of
      that care is provided by informal carers, a connection between social exclusion
      and informal care-receipt has rarely been considered. The aim of this study was
      to examine how informal care-receipt is related to social exclusion. A face-to
      face questionnaire survey on social exclusion and informal care-receipt was
      carried out among older people (n = 1255) living in Barnsley, United Kingdom.
      Multivariable analyses examined the association between social exclusion and
      categories of informal care-receipt: care-receiver; assurance-receiver;
      nonreceiver with no need; and nonreceiver with need. Compared to being a
      nonreceiver with no need, participants were more likely to be care-receivers or
      assurance-receivers if they had higher levels of social exclusion. The highest
      level of social exclusion, however, was found in nonreceivers with need. Despite
      a lack of informal care and support, formal practical support and personal care
      were also low in this latter group. Findings are discussed in relation to the
      conceptualisation of care-receipt and how contact with medical services could be
      an opportunity for identification and appropriate referral of nonreceivers with
      need.

PMID- 27882249
TI  - Surviving All Odds: A Unique Case of Multiple Congenital Unruptured Sinus of
      Valsalva Aneurysms Involving Both Left and Right Coronary Sinuses with
      Biventricular Dysfunction and Heart Block.
AB  - Aneurysms of the sinus of Valsalva are very uncommon, with an incidence ranging
      from 0.1 to 3.5% of all congenital heart defects. Very few cases have been
      reported in the literature that presented with involvement of two or more
      sinuses. We report a case of 27-year-old male with a history of exertional
      breathlessness of one-month duration. After complete evaluation using
      transesophageal echocardiography (TEE) and multiple detector computed tomography
      (MDCT) scanning, the patient was diagnosed to have large congenital unruptured
      sinus of Valsalva aneurysms involving both left and right coronary sinuses with
      extension into the interventricular septum. The patient also displayed second
      degree heart block (Mobitz type 2) and biventricular dysfunction. The patient was
      managed successfully. We present the case with an aim to highlight the management
      challenges including intraoperative and postoperative complications that are
      associated with unruptured sinus of Valsalva aneurysms of >=2 sinuses.

PMID- 27882250
TI  - Apical Revascularization after Delayed Tooth Replantation: An Unusual Case.
AB  - The aim of this paper is to present the clinical and radiological outcome of the
      treatment involving a delayed tooth replantation after an avulsed immature
      permanent incisor, with a follow-up of 1 year and 6 months. An 8-year-old boy was
      referred after dental trauma that occurred on the previous day. The permanent
      maxillary right central incisor (tooth 11) had been avulsed. The tooth was hand
      held during endodontic therapy and an intracanal medication application with
      calcium hydroxide-based paste was performed. An apical plug with mineral trioxide
      aggregate (MTA) was introduced into the apical portion of the canal. When the
      avulsed tooth was replanted with digital pressure, a blood clot had formed within
      the socket, which moved the MTA apical plug about 2 mm inside of the root canal.
      These procedures developed apical revascularization, which promoted a successful
      endodontic outcome, evidenced by apical closure, slight increase in root length,
      and absence of signs of external root resorption, during a follow-up of 1 year
      and 6 months.

PMID- 27882251
TI  - Bilateral Numb Chin Syndrome as the Initial Presentation of Burkitt's
      Lymphoma/Leukemia: A Report of Two Cases and Review of the Literature.
AB  - Numb chin syndrome, also known as mental nerve neuropathy, is a rare sensory
      neuropathy characterized by paresthesia and hypoesthesia in the area supplied by
      the mental nerve and its branches. This syndrome may be the first symptom of
      underlying malignancy or the first sign of recurrence and metastasis in patients
      with preexisting cancer. In this article, we present two cases with bilateral
      numb chin syndrome as the first manifestation of Burkitt's lymphoma/leukemia and
      review the relevant literature. Numb chin syndrome should be considered as a
      warning sign and raise the suspicion for an underlying malignancy. Bilateral
      involvement is especially hazardous and must not be underestimated. In fact, an
      astute neurologist and internist who realizes that chin numbness is a potentially
      significant symptom can then exclude serious underlying malignancies. Standard
      diagnostic protocol with different modalities of imaging based on the
      availability and experience of the radiology team should be mandatory. High index
      of suspicion should be practiced to avoid delay in diagnosis and progression of
      the underlying malignancy.

PMID- 27882252
TI  - Sjogren's Syndrome Complicated by Myeloid/Natural Killer Cell Precursor Acute
      Leukemia: Case Report and Review of the Literature.
AB  - We report a case of Sjogren's syndrome (SS) complicated by myeloid/natural killer
      (NK) cell precursor acute leukemia (M/NKPAL). A 75-year-old woman with a previous
      SS history for 2 years was routinely treated. Peripheral blood progenitor cells
      were increased, and subsequent bone marrow cell morphology examination showed the
      presence of acute myeloid leukemia type M4. However, flow cytometry analysis
      revealed that CD7/CD56/CD33/CD34/HLA-DR/cCD3 were all positive and
      myeloperoxidase- (MPO-) specific staining, other T cells, NK cells, and myeloid
      markers were all negative. Clonal T-cell receptor (TCR)beta/TCRgamma/TCRdelta
      gene rearrangements and Epstein-Barr virus (EBV) were negative. The diagnosis of
      M/NKPAL was therefore confirmed. Unfortunately, this patient did not receive
      chemotherapy and later died of acute left heart failure and respiratory failure.
      SS complication with M/NKPAL is relatively rare. Combined with the relevant
      literatures, our study offers new insights into the clinical characteristics,
      pathological features, possible pathogenesis, and differential diagnosis of this
      rare disease.

PMID- 27882253
TI  - Candida glabrata Pneumonia in a Patient with Chronic Obstructive Pulmonary
      Disease.
AB  - Pneumonia remains an important cause of morbidity and mortality among infectious
      diseases. Streptococcus pneumoniae and viruses are the most common cause of
      pneumonia. Candidiasis in such patients has been associated with haemodialysis,
      fungal colonization, exposure to broad-spectrum antibiotics, intensive care unit
      (ICU) hospitalization, and immunocompromised patients. The most common cause of
      infection is C. albicans. The case presented here is of a 66-year-old male
      patient diagnosed with C. glabrata. The patient suffered from chronic obstructive
      pulmonary disease.

PMID- 27882254
TI  - Nicolau Syndrome due to Penicillin Injection: A Report of 3 Cases without Long
      Term Complication.
AB  - Nicolau syndrome (NS) or livedo-like dermatitis is a rare complication of
      injection of various medications such as penicillin. The pathophysiology of this
      events is not clear, but some hypotheses are suggested, such as sympathetic nerve
      stimulation, embolic occlusion, inflammation, or mechanical injury. In this paper
      we report 3 cases of NS following benzathine penicillin. Clinical symptoms
      improved in 2 cases during 2-month follow-up, but one of them had a residual
      necrosis in the distal phalanges of the toes.

PMID- 27882255
TI  - Tip of an Iceberg: Skull Fracture as an Adult Presentation of
      Encephalocraniocutaneous Lipomatosis.
AB  - The severity of seizures presenting to the emergency department ranges from
      benign to life threatening. There are also a wide number of possible etiologies.
      Computed tomography (CT) emergency imaging may be required at presentation to
      elucidate a possible cause and assess signs of intracranial trauma. This case
      describes a serious seizure episode in a young man while on holiday. A CT brain
      showed a skull fracture as a consequence of seizure-related head trauma but
      unexpectedly there were image findings consistent with encephalocraniocutaneous
      lipomatosis. The important radiological features of encephalocraniocutaneous
      lipomatosis and a differential diagnosis are presented.

PMID- 27882256
TI  - EEG-Triggered Functional Electrical Stimulation Therapy for Restoring Upper Limb
      Function in Chronic Stroke with Severe Hemiplegia.
AB  - We report the therapeutic effects of integrating brain-computer interfacing
      technology and functional electrical stimulation therapy to restore upper limb
      reaching movements in a 64-year-old man with severe left hemiplegia following a
      hemorrhagic stroke he sustained six years prior to this study. He completed 40 90
      minute sessions of functional electrical stimulation therapy using a custom-made
      neuroprosthesis that facilitated 5 different reaching movements. During each
      session, the participant attempted to reach with his paralyzed arm repeatedly.
      Stimulation for each of the movement phases (e.g., extending and retrieving the
      arm) was triggered when the power in the 18 Hz-28 Hz range (beta frequency range)
      of the participant's EEG activity, recorded with a single electrode, decreased
      below a predefined threshold. The function of the participant's arm showed a
      clinically significant improvement in the Fugl-Meyer Assessment Upper Extremity
      (FMA-UE) subscore (6 points) as well as moderate improvement in Functional
      Independence Measure Self-Care subscore (7 points). The changes in arm's function
      suggest that the combination of BCI technology and functional electrical
      stimulation therapy may restore voluntary motor function in individuals with
      chronic hemiplegia which results in severe upper limb deficit (FMA-UE <= 15), a
      population that does not benefit from current best-practice rehabilitation
      interventions.

PMID- 27882258
TI  - Dysmorphic Facial Features and Other Clinical Characteristics in Two Patients
      with PEX1 Gene Mutations.
AB  - Peroxisomal disorders are a group of genetically heterogeneous metabolic diseases
      related to dysfunction of peroxisomes. Dysmorphic features, neurological
      abnormalities, and hepatic dysfunction can be presenting signs of peroxisomal
      disorders. Here we presented dysmorphic facial features and other clinical
      characteristics in two patients with PEX1 gene mutation. Follow-up periods were
      3.5 years and 1 year in the patients. Case I was one-year-old girl that presented
      with neurodevelopmental delay, hepatomegaly, bilateral hearing loss, and visual
      problems. Ophthalmologic examination suggested septooptic dysplasia. Cranial
      magnetic resonance imaging (MRI) showed nonspecific gliosis at subcortical and
      periventricular deep white matter. Case II was 2.5-year-old girl referred for
      investigation of global developmental delay and elevated liver enzymes.
      Ophthalmologic examination findings were consistent with bilateral nystagmus and
      retinitis pigmentosa. Cranial MRI was normal. Dysmorphic facial features
      including broad nasal root, low set ears, downward slanting eyes, downward
      slanting eyebrows, and epichantal folds were common findings in two patients.
      Molecular genetic analysis indicated homozygous novel IVS1-2A>G mutation in Case
      I and homozygous p.G843D (c.2528G>A) mutation in Case II in the PEX1 gene.
      Clinical findings and developmental prognosis vary in PEX1 gene mutation. Kabuki
      like phenotype associated with liver pathology may indicate Zellweger spectrum
      disorders (ZSD).

PMID- 27882257
TI  - A Hormonally Active Malignant Struma Ovarii.
AB  - Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at
      least 50% thyroid tissue. Less than 8% of struma ovarii cases present with
      clinical and biochemical evidence of thyrotoxicosis due to ectopic production of
      thyroid hormone and only 5% undergo malignant transformation into a papillary
      thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid
      carcinoma developing within a struma ovarii have been reported in the literature.
      We report the case of a 36-year-old woman who presented with clinical signs and
      symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a
      thyroid hormone-producing, malignant struma ovarii.

PMID- 27882259
TI  - Right Lung Agenesis with Tracheal Stenosis due to Complete Tracheal Rings and
      Postpneumonectomy Like Syndrome Treated with Tissue Expander Placement.
AB  - Congenital lung agenesis is an extremely rare condition with an estimated
      prevalence of 34 in 1,000,000 live births. It is often associated with other
      congenital malformations of the skeletal, cardiovascular, urogenital, and
      gastrointestinal systems. We discuss the case of a 5-month-old who presented with
      increasing stridor over 1 month. Imaging revealed right lung agenesis, complete
      dextromalposition of heart, and compression of distal trachea. An intrathoracic
      saline tissue expander was placed which marked improved distal tracheal stenosis.
      In patients who are symptomatic it becomes imperative to perform surgeries to
      increase survival as was the case in this patient.

PMID- 27882260
TI  - Intrascrotal Collection in an Acute Pancreatitis: A Case Report and Review of the
      Literature.
AB  - Context. An inguinoscrotal swelling occurring during an acute pancreatitis is
      very rare. Case Report. We report a case of right inguinoscrotal swelling
      appearing in connection with an interstitial edematous acute pancreatitis. We
      have noticed a spontaneous complete reduction of the right inguinoscrotal
      swelling after 10 days. Conclusion. The management of a scrotal swelling should
      be the least invasive possible method but also the most complete possible method
      to avoid unnecessary interventions. The exclusion of a pathology that could
      affect the vital prognosis of the testis remains the absolute priority. An acute
      scrotum swelling must be carried out by the clinical management by a professional
      and must be completed with an ultrasonography of the scrotum. Despite all that,
      if the original etiology of the acute scrotum remains unknown, an abdominopelvic
      CT scan could provide more details and so could offer a different diagnosis of
      exclusion, different from the diagnosis of acute idiopathic scrotal edema (AISE).
      This rare complication of acute pancreatitis reported could be mistaken for a
      more common pathology. If that complication is identified, it will not require a
      surgical intervention if there is a correct management of the acute pancreatitis
      which could justify a broader CT scan.

PMID- 27882261
TI  - Prevalence of Hepatitis C Virus Seropositivity and Its Impact on Coronary Artery
      Disease among Egyptian Patients Referred for Coronary Angiography.
AB  - Background. We tested the prevalence and impact of HCV seropositivity among
      Egyptian patients referred for coronary angiography. Subjects and Methods. This
      cross-sectional study was conducted in Zagazig University hospitals including 509
      patients scheduled for elective coronary angiography between June 2013 and June
      2014. By taking full history on admission, laboratory workup including HCV Ab,
      echocardiography study, and coronary angiography, we calculated the mean number
      of coronary artery lesions and the mean number of affected coronary artery
      vessels for all patients. The severity of the coronary lesions was estimated
      using the Gensini score. Results. HCV seropositive patients referred for coronary
      angiography were about 30.3% (which is greater than the prevalence of HCV
      seropositivity among general population in Egypt), patients proved to have CAD
      who are HCV antibody positive had more severe coronary lesions than in
      seronegative one (p < 0.05), and patients proved to have CAD who are HCV antibody
      positive had comparable prevalence of cardiovascular risk factors as seronegative
      patients except for diabetes and hypertension which are more prevalent in
      seronegative patients (p < 0.05). Conclusion. Prevalence of HCV antibody positive
      patients referred for coronary angiography was about 30.3%, and CAD patients who
      are HCV antibody positive had more severe coronary lesions and less prevalence of
      diabetes and hypertension than HCV antibody negative.

PMID- 27882262
TI  - Knowledge of Stroke Risk Factors among Stroke Survivors in Nigeria.
AB  - Background. Knowledge of stroke risk factors is expected to reduce the incidence
      of stroke-whether first-ever or recurrent. This study examined knowledge of
      stroke risk factors and its determinants among stroke survivors. Methods. A cross
      sectional survey of consenting stroke survivors at two physiotherapy facilities
      in Nigeria was carried out. Sociodemographic and clinical data were obtained and
      knowledge of stroke risk factors (defined as the ability to mention at least one
      correct risk factor) was assessed using open-ended questionnaire. Data were
      treated with descriptive statistics and logistic regression analysis. Results.
      Sixty-nine stroke survivors (male = 72.5%; mean +/- SD age = 49.7 +/- 10.6 years)
      participated in the study. Thirty-four (49.4%) participants had knowledge of
      stroke risk factors. Only educational level was significantly associated with
      knowledge and participants with tertiary educational qualification were about 48
      times (odds ratio = 48.5; CI = 7.6-309.8; P < 0.0001) more likely to be
      knowledgeable than those with no education. Conclusion. Less than half of the
      participants had knowledge of stroke risk factors. Participants with tertiary
      education were significantly more knowledgeable than those with lower educational
      qualifications. Effective means of educating stroke survivors on stroke risk
      factors should be identified and adopted.

PMID- 27882263
TI  - Electrochemical Study of Carbon Nanotubes/Nanohybrids for Determination of Metal
      Species Cu2+ and Pb2+ in Water Samples.
AB  - The use of nanomaterials, such as nanoparticles and nanotubes, for
      electrochemical detection of metal species has been investigated as a way of
      modifying electrodes by electrochemical stripping analysis. The present study
      develops a new methodology based on a comparative study of nanoparticles and
      nanotubes with differential pulse anodic stripping voltammetry (DPASV) and
      examines the simultaneous determination of copper and lead. The glassy carbon
      electrode modified by gold nanoparticles demonstrated increased sensitivity and
      decreased detection limits, among other improvements in analytical performance
      data. Under optimized conditions (deposition potential -0.8 V versus Ag/AgCl;
      deposition time, 300 s; resting time, 10 s; pulse amplitude, 50 mV; and voltage
      step height, 4 mV), the detection limits were 0.2279 and 0.3321 ppb,
      respectively, for determination of Pb2+ and Cu2+. The effects of cations and
      anions on the simultaneous determination of metal ions do not exhibit significant
      interference, thereby demonstrating the selectivity of the electrode for
      simultaneous determination of Pb2+ and Cu2+. The same method was also used to
      determine Cu2+ in water samples.

PMID- 27882264
TI  - Observation of Strong Reflection of Electron Waves Exiting a Ballistic Channel at
      Low Energy.
AB  - Wave scattering by a potential step is a ubiquitous concept. Thus, it is
      surprising that theoretical treatments of ballistic transport in nanoscale
      devices, from quantum point contacts to ballistic transistors, assume no
      reflection even when the potential step is encountered upon exiting the device.
      Experiments so far seem to support this even if it is not clear why. Here we
      report clear evidence of coherent reflection when electron wave exits the channel
      of a nanoscale transistor and when the electron energy is low. The observed
      behavior is well described by a simple rectangular potential barrier model which
      the Schrodinger's equation can be solved exactly. We can explain why reflection
      is not observed in most situations but cannot be ignored in some important
      situations. Our experiment also represents a direct measurement of electron
      injection velocity - a critical quantity in nanoscale transistors that is widely
      considered not measurable.

PMID- 27882265
TI  - Blood Derived Induced Pluripotent Stem Cells (iPSCs): Benefits, Challenges and
      the Road Ahead.
AB  - Since the creation of induced Pluripotent Stem Cells (iPSCs) ten years ago,
      hundreds of publications have demonstrated their considerable impact on disease
      modeling and therapy. In this commentary, we will summarize key milestones,
      benefits and challenges in the iPSC field. Furthermore, we will highlight blood
      as an effective and easily accessible source for patient-specific iPSCs
      derivation in the context of work done in our laboratory and others.

PMID- 27882266
TI  - Community Interventions to Improve Cooking Skills and Their Effects on Confidence
      and Eating Behaviour.
AB  - PURPOSE OF REVIEW: Community-based interventions aiming to improve cooking skills
      are a popular strategy to promote healthy eating. We reviewed current evidence on
      the effectiveness of these interventions on different confidence aspects and
      fruit and vegetable intake. RECENT FINDINGS: Evaluation of cooking programmes
      consistently report increased confidence in cooking skills in adults across
      different age groups and settings. The effectiveness of these programmes on
      modifying eating behaviour is less consistent, but small increases in self
      reported consumption of fruit and vegetables are also described. Lack of large
      samples, randomization and control groups and long-term evaluation are
      methodological limitations of the evidence reviewed. SUMMARY: Cooking skill
      interventions can have a positive effect on food literacy, particularly in
      improving confidence on cooking and fruit and vegetable consumption, with
      vulnerable, low-socieconomic groups gaining more benefits. Consistency across
      study designs, delivery and evaluation of outcomes both at short and long terms
      are warranted to draw clearer conclusions on how cooking programmes are
      contributing to improve diet and health.

PMID- 27882269
TI  - Concomitant Lumbar Stenosis and Aortic Pseudoaneurysm: A Case Report.
AB  - Aortic pseudoaneurysm can create a constellation of symptoms that can mimic
      lumbar back pain. There are rare but well-documented reports of aortic pathology
      (aneurysms, pseudoaneurysms, and chronic contained aneurysm ruptures) eroding
      into the vertebral column causing neural compression. We report a case of a
      rapidly progressive aortic pseudoaneurysm in a patient with pre-existing lumbar
      spine pathology which had the potential for catastrophic intraoperative bleeding
      during a minimally invasive surgery (MIS) using the transforaminal lumbar
      interbody fusion (TLIF) technique. Postoperatively, the patient's radicular pain
      resolved but her back pain remained. Further workup identified the pseudoaneurysm
      and the patient subsequently underwent open vascular repair. In this report, we
      highlight a lesser known mimicker of lumbar back pain.

PMID- 27882267
TI  - Microvesicles as Vehicles for Tissue Regeneration: Changing of the Guards.
AB  - PURPOSE OF REVIEW: Microvesicles (MVs) have been recognised as mediators of stem
      cell function, enabling and guiding their regenerative effects. RECENT FINDINGS:
      MVs constitute one unique size class of extracellular vesicles (EVs) directly
      shed from the cell plasma membrane. They facilitate cell-to-cell communication
      via intercellular transfer of proteins, mRNA and microRNA (miRNA). MVs derived
      from stem cells, or stem cell regulatory cell types, have proven roles in tissue
      regeneration and repair processes. Their role in the maintenance of healthy
      tissue function throughout the life course and thus in age related health span
      remains to be elucidated. SUMMARY: Understanding the biogenesis and mechanisms of
      action of MVs may enable the development of cell-free therapeutics capable of
      assisting in tissue maintenance and repair for a variety of age-related
      degenerative diseases. This review critically evaluates recent work published in
      this area and highlights important new findings demonstrating the use of MVs in
      tissue regeneration.

PMID- 27882270
TI  - Impact of Race/Ethnicity on Pain Management Outcomes in a Community-Based
      Teaching Hospital Following Inpatient Palliative Care Consultation.
AB  - OBJECTIVE: To examine race/ethnicity differences in pain management outcomes
      following inpatient palliative care consultation. METHODS: We conducted a
      retrospective study based on data from a community-based teaching hospital in
      Fresno, CA, USA, from April 2014 to July 2015. One hundred sixty-one patients
      with life-limiting diagnoses and palliative care pain-related consultations were
      included. The patients were categorized into four racial groups: Caucasians,
      African-Americans, Hispanics, and Asians/Others. Demographics and baseline pain
      scores using the Visual Analogue Scale (VAS) were obtained. The outcome measures
      included the length of stay, time to consult, and pain scores at admission, 24
      hours before the consultation, 24-48 hours after consultation, and at discharge.
      RESULTS: The initial median pain scores were not significantly different between
      the groups, however, the Asians had slightly higher pain scores compared to the
      other groups. African-Americans, Caucasians, and Hispanics had significant
      differences in pain outcomes after consultation compared to 24 hours prior to
      consultation (p = 0.01, p < 0.01 and p = 0.02, respectively). Caucasians and
      Hispanics had significant differences in pain outcomes after palliative
      consultation compared to initial admission assessment (p < 0.01). The differences
      between discharge and admission pain scores were significant only for Asians,
      Caucasians, and Hispanics (p = 0.04, p < 0.01, p < 0.01, respectively) but not
      African-Americans. There were no significant pain score differences across the
      racial groups following consultations. CONCLUSION: There were no significant
      differences in pain reduction amongst the racial groups, suggesting that pain can
      adequately be managed in individual racial groups after inpatient palliative care
      consultations.

PMID- 27882268
TI  - Long-Term Culture of Intestinal Cell Progenitors: An Overview of Their
      Development, Application, and Associated Technologies.
AB  - PURPOSE OF REVIEW: Long-term culture of adult progenitor cells in 3D is a
      recently emerging technology that inhabits the space between 2D cell lines and
      organ slice culture. RECENT FINDINGS: Adaptations to defined media components in
      the wake of advances in ES and iPS cell culture has led to the identification of
      conditions that maintained intestinal cell progenitors in culture. These
      conditions retain cellular heterogeneity of the normal or tumour tissue, and the
      cultures have been shown to be genetically stable, such that substantial biobanks
      are being created from patient derived material. This coupled with advances in
      analytical tools has generated a field, characterized by the term "organoid
      culture", that has huge potential for advancing drug discovery, regenerative
      medicine, and furthering the understanding of fundamental intestinal biology.
      SUMMARY: In this review, we describe the approaches available for the long-term
      culture of intestinal cells from normal and diseased tissue, the current
      challenges, and how the technology is likely to develop further.

PMID- 27882271
TI  - The Hidden Culprit in a Massive Episode of Hematemesis: A Dieulafoy's Lesion.
AB  - A Dieulafoy's lesion is described as a tortuous, dilated aberrant submucosal
      vessel that can penetrate through the mucosa and rupture spontaneously, resulting
      in severe gastrointestinal bleeding. The lesion is most commonly found in the
      proximal stomach. Historically, it has had up to an 80% mortality rate because of
      its tendency to cause intermittent but severe bleeding and diagnostic challenges.
      We report a case of a young male with recurrent severe upper gastrointestinal
      bleeding with extensive prior investigations failing to reveal the source of
      bleeding. Computed tomography angiography of the abdomen correctly identified
      Dieulafoy's lesion of the stomach, and it was subsequently confirmed and
      successfully treated with interventional radiology (IR)-guided mesenteric
      angiography and embolization.

PMID- 27882272
TI  - The Impact of Wearable Device Enabled Health Initiative on Physical Activity and
      Sleep.
AB  - OBJECTIVES: The Personal Health Management Study (PHMS) is an assessment of the
      effect of a voluntary employee-facing health initiative using a commercially
      available wearable device implemented among 565 employees of Boehringer Ingelheim
      Pharmaceuticals, Inc. The results of the initiative on physical activity
      (measured as steps) and sleep is reported. METHODS: This was a 12-month,
      prospective, single-cohort intervention study using a wearable activity-measuring
      device tracking steps and sleep (entire study period) and a system of health
      promoting incentives (first nine months of study period). The findings from the
      first nine study months are reported. RESULTS: The mixed model repeated measures
      approach was used to analyze the data. There was no significant difference in
      steps between the first month (7915.6 mean steps per person per day) and the last
      month (7853.4 mean steps per person per day) of the intervention. However, there
      was a seasonal decline in steps during the intervention period from fall to
      winter, followed by an increase in steps from winter to spring. In contrast,
      sleep tended to increase steadily throughout the study period, and the number of
      hours slept during the last month (7.52 mean hours per person per day) of the
      intervention was significantly greater than the number of hours slept during the
      first month (7.16 mean hours per person per day). CONCLUSIONS: The impact of the
      initiative on physical activity and sleep differed over the period of time
      studied. While physical activity did not change between the first and last month
      of the intervention, the number of hours slept per night increased significantly.
      Although seasonal changes and study-device habituation may explain the pattern of
      change in physical activity, further evaluation is required to clarify the
      reasons underlying the difference in the impact of the initiative on the dynamics
      of steps and sleep.

PMID- 27882273
TI  - Rural Medical Education in New Zealand.
AB  - Despite a large number of yearly medical graduates, rural New Zealand is faced
      with a scarcity of practicing physicians. Opportunities to learn and practice in
      rural settings start at the undergraduate level and extend to practicing
      physicians. There are a number of different programs available to facilitate
      rural medical education for all students and physicians. These programs will be
      discussed in this article.

PMID- 27882274
TI  - Mechanics of Wound Closure: Emerging Tape-Based Wound Closure Technology vs.
      Traditional Methods.
AB  - To date, there is still a lack of understanding of how wound closure methods
      perform comparatively under daily bodily movement during the course of healing
      and how they affect the mechanics of healing. The present study is a first step
      in understanding and objectively quantifying the gap. The study provides both a
      new method of metrology for noninvasive evaluation of skin mechanics at the onset
      of wound healing and an emerging tape-based wound closure technology. The latter
      shows better performance with respect to commonly used staples and sutures,
      holding the wound intact and providing uniform mechanical support across the
      incision.

PMID- 27882275
TI  - A Case of an Enigmatic Pulmonary Infiltrate.
AB  - The differential diagnosis of a pulmonary mass in an immunosuppressed host with a
      history of cancer is broad and includes malignant, infectious and inflammatory
      etiologies. Mycobacterium avium complex (MAC) is a rare cause of opportunistic
      infection in susceptible individuals that can present as either localized or
      disseminated disease. On radiologic studies, the pulmonary disease can manifest
      as heterogeneous linear or nodular densities, a mass-like lesion, or thin-walled
      cavitary lesions. We present the case of pulmonary MAC in a patient with a
      history of lung cancer requiring lobectomy, and splenic lymphoma being treated
      with chemotherapy, presenting with extreme fatigue and a fludeoxyglucose (FDG)
      avid mass on positron emission tomography-computed tomography (PET-CT). The
      patient had a CT-guided biopsy of the mass that demonstrated non-caseating
      granulomas followed by a right middle lobe transbronchial biopsy that upon
      histologic examination revealed mild acute and chronic inflammation, and
      necrotizing caseating granulomas. The acid-fast culture of bronchoalveolar lavage
      showed the growth of acid-fast bacilli that were identified by deoxyribonucleic
      acid (DNA) probe as Mycobacterium avium complex. We discuss the typical
      radiological manifestations of MAC as well as the role of immunosuppression and B
      cell-depleting therapy from the predisposition to infection.

PMID- 27882276
TI  - Isolated Non-Traumatic Bilateral Coronoid Process Fracture of the Mandible.
AB  - Isolated bilateral fractures of the coronoid processes of the mandible occurred
      in this patient without any significant trauma. The definite etiology of this
      case is unknown, but possible causes or contributing factors may include acute
      reflex contraction of the patient's temporalis muscles leading to bilateral
      stress fractures, coronoid process hyperplasia, or the patient's long-term use of
      omeprazole. The planned treatment for this patient included pain control with
      Mobic and tramadol and splint fabrication followed by arch bar placement with
      training elastics for six weeks.

PMID- 27882278
TI  - Heat transfer analysis of underground U-type heat exchanger of ground source heat
      pump system.
AB  - BACKGROUND: Ground source heat pumps is a building energy conservation technique.
      The underground buried pipe heat exchanging system of a ground source heat pump
      (GSHP) is the basis for the normal operation of an entire heat pump system.
      METHODS: Computational-fluid-dynamics (CFD) numerical simulation software, ANSYS
      FLUENT17.0 have been performed the calculations under the working conditions of a
      continuous and intermittent operation over 7 days on a GSHP with a single-well,
      single-U and double-U heat exchanger and the impact of single-U and double-U
      buried heat pipes on the surrounding rock-soil temperature field and the impact
      of intermittent operation and continuous operation on the outlet water
      temperature. CONCLUSIONS: The influence on the rock-soil temperature is
      approximately 13 % higher for the double-U heat exchanger than that of the single
      U heat exchanger. The extracted energy of the intermittent operation is 36.44
      kw.h higher than that of the continuous mode, although the running time is lower
      than that of continuous mode, over the course of 7 days. The thermal interference
      loss and quantity of heat exchanged for unit well depths at steady-state
      condition of 2.5 De, 3 De, 4 De, 4.5 De, 5 De, 5.5 De and 6 De of sidetube
      spacing are detailed in this work. The simulation results of seven working
      conditions are compared. It is recommended that the side-tube spacing of double-U
      underground pipes shall be greater than or equal to five times of outer diameter
      (borehole diameter: 180 mm).

PMID- 27882277
TI  - Effect of silver nanoparticles on the standard soil arthropod Folsomia candida
      (Collembola) and the eukaryote model organism Saccharomyces cerevisiae.
AB  - BACKGROUND: Because of their antimicrobial properties, silver nanoparticles
      (AgNPs) have been widely used and have come into contact with the environment. In
      the present work, an effect of AgNPs on a standard soil organism, Folsomia
      candida, was studied (in comparison to silver nitrate) focusing on molecular and
      cellular alterations as ecotoxicological endpoints. RESULTS: At the molecular
      level, an up-regulation of metallothionein-containing protein (MTC) mRNA in AgNP
      treated groups indicated toxic heavy metal stress effects caused by the release
      of silver ions from AgNPs, which is similar to animal groups treated with silver
      nitrate. Alteration of the steady-state level of glutathione S-transferase (GST)
      mRNA was detected in animal treated with AgNPs and AgNO3. At the cellular level,
      the relation between GST activity and the size of the glutathione (GSH) was
      examined. Change of GST activity from different animal groups was not
      significant, whereas the GSH pool (reduced and oxidized forms) decreased with
      increasing concentration of AgNPs. In order to obtain direct evidence whether
      AgNPs cause oxidative stress, treated animals were incubated with the non
      fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). A
      fluorescence signal was observed in both AgNPs- and AgNO3-treated groups pointing
      to the production of reactive species (RS). Since RS formation in F.candida is
      difficult to quantify, yeast strain BY4742 (wild-type) and mutants lacking of
      oxidative stress-related protective enzymes were exploited as a further eukaryote
      model organism. AgNPs and AgNO3 were found to also affect growth of yeast and
      induced oxidative stress. CONCLUSIONS: An effect of AgNPs on Collembola and yeast
      strains is similar to the one from AgNO3. However, AgNPs is less toxic due to the
      slow release of silver ions. In summary, the toxic effect of AgNPs on F. candida
      is caused by the combination of the release of silver ions from AgNPs and the
      formation of reactive species.

PMID- 27882280
TI  - Existence of common fixed point and best proximity point for generalized
      nonexpansive type maps in convex metric space.
AB  - Here, we extend the notion of (E.A.) property in a convex metric space defined by
      Kumar and Rathee (Fixed Point Theory Appl 1-14, 2014) by introducing a new class
      of self-maps which satisfies the common property (E.A.) in the context of convex
      metric space and ensure the existence of common fixed point for this newly
      introduced class of self-maps. Also, we guarantee the existence of common best
      proximity points for this class of maps satisfying generalized non-expansive type
      condition. We furnish an example in support of the proved results.

PMID- 27882279
TI  - Research on the water-entry attitude of a submersible aircraft.
AB  - BACKGROUND: The water entry of a submersible aircraft, which is transient, highly
      coupled, and nonlinear, is complicated. After analyzing the mechanics of this
      process, the change rate of every variable is considered. A dynamic model is
      build and employed to study vehicle attitude and overturn phenomenon during water
      entry. Experiments are carried out and a method to organize experiment data is
      proposed. The accuracy of the method is confirmed by comparing the results of
      simulation of dynamic model and experiment under the same condition. RESULTS:
      Based on the analysis of the experiment and simulation, the initial attack angle
      and angular velocity largely influence the water entry of vehicle. Simulations of
      water entry with different initial and angular velocities are completed, followed
      by an analysis, and the motion law of vehicle is obtained. To solve the problem
      of vehicle stability and control during water entry, an approach is proposed by
      which the vehicle sails with a zero attack angle after entering water by
      controlling the initial angular velocity. With the dynamic model and optimization
      research algorithm, calculation is performed, and the optimal initial angular
      velocity of water-entry is obtained. CONCLUSIONS: The outcome of simulations
      confirms that the effectiveness of the propose approach by which the initial
      water-entry angular velocity is controlled.

PMID- 27882281
TI  - The computation of confidence intervals for the state parameters of power
      systems.
AB  - BACKGROUND: In the past few decades, a significant volume of work has been
      carried out on various aspects of the state estimation problem to estimate an
      optimum state vector of the power system. This problem has been focused on, in
      previous studies regarding the computational efficiency and numerical robustness
      in view to find point estimates for system state parameters. This current
      investigation, constructed confidence intervals for the unknown state parameters
      of the system. The research indicates that confidence intervals can yield
      addition useful information about the estimated parameters. METHODS: The feasible
      interval estimates for the system state parameters have been modelled in this
      study by considering the random uncertainty in the processing measurements. The
      statistical assumptions of the measurement errors have been utilized to
      characterize the probabilistic behavior of the estimated parameters in terms of
      confidence intervals. The Gauss-Newton algorithm has been adopted for maximizing
      the likelihood function of the processing measurements and obtaining the
      confidence intervals. RESULTS: The usage of the confidence intervals was
      demonstrated through Monte Carlo experiments on a real dataset of the 6-bus and
      IEEE 14-bus power systems for both small and large sample sizes. The confidence
      intervals were constructed for the test networks for the sample of measurements
      18, 28, 44 and 68 based on the redundancy ratio R. The proposed interval
      estimates outperformed for the sample sizes of 28 in the 6 bus and 68 in the IEEE
      14-bus systems, respectively. The poor performance for the constructed interval
      estimates have been reported even for the large sample sizes in the existence of
      contaminated measurements. CONCLUSIONS: The results of the study show that the
      method is effective and practically applicable in the state estimation of a power
      system. The constructed confidence intervals for the system state parameters
      adequately perform for the lager sample size. However, the existence of the gross
      errors in the processing measurements had severe effect on the performance of the
      proposed interval estimates.

PMID- 27882283
TI  - Blocks in cycles and k-commuting permutations.
AB  - We introduce and study k-commuting permutations. One of our main results is a
      characterization of permutations that k-commute with a given permutation. Using
      this characterization, we obtain formulas for the number of permutations that k
      commute with a permutation [Formula: see text], for some cycle types of [Formula:
      see text]. Our enumerative results are related with integer sequences in "The On
      line Encyclopedia of Integer Sequences", and in some cases provide new
      interpretations for such sequences.

PMID- 27882282
TI  - Preliminary study on biology and feeding capacity of Chelisoches morio
      (Fabricius) (Dermaptera:Chelisochidae) on Tirathaba rufivena (Walker).
AB  - BACKGROUND: Chelisoches morio (Fabricius) (Dermaptera:Chelisochidae) is an
      important predator of Tirathaba rufivena (Walker) (Lepidoptera:Pyralidae). For
      better use of the natural enemy, a biological study on C. morio was conducted,
      particularly its developmental duration, survival, fecundity and sex ratio. And
      the feeding capacity of C. morio against T. rufivena was also studied under
      laboratory conditions. RESULTS: The biological study on C. morio was revealed
      that female adults usually lay eggs in egg masses. The number of eggs per female
      averaged 140.17 eggs, and the incubation period was 7.50 days. The duration of
      nymphal development included four instars. The immature period was 83.95 days.
      The longevity of males and females was 58.60 and 93.55 days, respectively. The
      results from the study on the feeding capacity of C. morio using T. rufivena as
      food revealed that C. morio adults could consume 11.08, 7.87, 7.09, 6.82 and 5.89
      first-to-fifth-instar T. rufivena larvae, respectively. CONCLUSIONS: C. morio
      showed a huge amount of predation on this pest at all larval stages, implying a
      significant potential for the use of C. morio in controlling T. rufivena.

PMID- 27882284
TI  - Soft normed rings.
AB  - Molodtsov introduced the concept of soft sets, which can be seen as a new
      mathematical tool for dealing with uncertainty. In this paper, we initiate the
      study of soft normed rings by soft set theory. The notions of soft normed rings,
      soft normed ideals, soft complete normed rings are introduced and also several
      related properties and examples are given.

PMID- 27882285
TI  - Reliability of digital reactor protection system based on extenics.
AB  - After the Fukushima nuclear accident, safety of nuclear power plants (NPPs) is
      widespread concerned. The reliability of reactor protection system (RPS) is
      directly related to the safety of NPPs, however, it is difficult to accurately
      evaluate the reliability of digital RPS. The method is based on estimating
      probability has some uncertainties, which can not reflect the reliability status
      of RPS dynamically and support the maintenance and troubleshooting. In this
      paper, the reliability quantitative analysis method based on extenics is proposed
      for the digital RPS (safety-critical), by which the relationship between the
      reliability and response time of RPS is constructed. The reliability of the RPS
      for CPR1000 NPP is modeled and analyzed by the proposed method as an example. The
      results show that the proposed method is capable to estimate the RPS reliability
      effectively and provide support to maintenance and troubleshooting of digital RPS
      system.

PMID- 27882286
TI  - Technical application for inspection sampling for repairable systems in an
      economic system.
AB  - In this article we develop a model for determining the appropriate level of
      inspection sampling for any manufacturing process. The model is useful for
      manufacturers, who naturally are concerned with profits and therefore with
      minimizing the cost of production. The model design aims to reduce total
      manufacturing cost and has general applicability to various manufacturing
      operations. The model considers the interests of consumers, who wish to minimize
      the cost of production while simultaneously ensuring the final product is of high
      quality. The cost parameters for production, the acceptance test, and admissible
      strategy are applied in the model. The cost components are formulated along with
      the minimization of the expected cost, and we used the repairable systems to
      guarantee the maintenance and sustainability of the economic system. We also
      discuss the assumptions and their appropriateness, as well as the application of
      the model to burn-in of system components.

PMID- 27882287
TI  - Oscillation and asymptotic properties of a class of second-order Emden-Fowler
      neutral differential equations.
AB  - We consider a class of second-order Emden-Fowler equations with positive and
      nonpositve neutral coefficients. By using the Riccati transformation and
      inequalities, several oscillation and asymptotic results are established. Some
      examples are given to illustrate the main results.

PMID- 27882288
TI  - Using Benefit-Cost Analysis to Scale Up Early Childhood Programs through Pay-for
      Success Financing.
AB  - Increasing access to high-quality preschool programs is a high priority at local,
      state, and federal levels. Recently, two initiatives to expand preschool
      programming in Illinois and Utah have used funds from private investors to scale
      up existing programs. Private-sector social impact investors provide funding to
      nonprofit or public preschool providers to increase the number of children
      served. If the measured outcomes from preschool participation meet pre-determined
      goals, then the estimated government cost savings arising from these preschool
      interventions are used to repay the investors. Social impact investing with a
      "Pay for Success" contract can help budget-constrained governments expand proven
      or promising preventive interventions without the need to increase taxes. Cost
      benefit analysis plays a crucial role in helping to identify which social,
      educational or health interventions are suitable for this type of innovative
      financing. Cost-benefit analysts are needed to design the structure of the
      success payments that the government will make to the private investors. This
      paper describes social impact borrowing as a new method for financing public
      services, outlines the contribution of cost-benefit analysis, and discusses the
      innovative use of social impact financing to promote scaling up of the evidence
      based Child Parent Centers and other early childhood programs.

PMID- 27882289
TI  - Integrated assembly and motion planning using regrasp graphs.
AB  - This paper presents an integrated assembly and motion planning system to
      recursively find the assembly sequence and motions to assemble two objects with
      the help of a horizontal surface as the supporting fixture. The system is
      implemented in both assembly level and motion level. In the assembly level, the
      system checks all combinations of the assembly sequences and gets a set of
      candidates. Then, for each candidate assembly sequence, the system incrementally
      builds regrasp graphs and performs recursive search to find a pick-and-place
      motion in the motion level to manipulate the base object as well as to assemble
      the other object to the base. The system integrates the candidate assembly
      sequences computed in the assembly level incrementally and recursively with graph
      searching and motion planning in the motion level and plans the assembly
      sequences and motions integratedly for assembly tasks. Both simulation and real
      world experiments are performed to demonstrate the efficacy of the integrated
      planning system.

PMID- 27882290
TI  - Mast Cell Interaction with Neutrophils in Human Gastric Carcinomas:
      Ultrastructural Observations.
AB  - Aim. The role of mast cells in cell-cell immune interactions has received
      increasing attention, although their functional interaction with neutrophils
      still remains to be clarified in tumors. The aim of the present study was to
      investigate the association between mast cells and neutrophils in a series of
      gastric carcinomas (GC). Patients and Methods. 52 surgically resected GC
      specimens were routinely processed for both light and electron microscopy. Only
      cases showing both mast cells and neutrophils in the tumor stroma were considered
      in the analysis. Results. Only 9 GC (M : F = 5 : 4; age range: 50-82 years)
      showed both mast cells and neutrophils in the tumor stroma. At ultrathin
      sections, we identified heterotypic aggregation and intermingling of mast cells
      and neutrophils. Mast cells had mature phenotype and showed full complement of
      granules with homogeneous, scroll, particle, and mixed pattern. In addition, we
      found normal-appearing or early apoptosis showing neutrophils. Conclusion. Our
      histological findings showed the likely interaction between mast cells and
      neutrophils in GC. We hypothesize that the granular content of mast cells may be
      released in small quantity through a mechanism called "kiss-and-run fusion,"
      which is alternative to well-known massive anaphylactic or piecemeal
      degranulation.

PMID- 27882291
TI  - Comparison of body mass index, waist circumference, and waist to height ratio in
      the prediction of hypertension and diabetes mellitus: Filipino-American women
      cardiovascular study.
AB  - The relative ability of three obesity indices to predict hypertension (HTN) and
      diabetes (DM) and the validity of using Asian-specific thresholds of these
      indices were examined in Filipino-American women (FAW). Filipino-American women
      (n = 382), 40-65 years of age were screened for hypertension (HTN) and diabetes
      (DM) in four major US cities. Body mass index (BMI), waist circumference (WC) and
      waist circumference to height ratio (WHtR) were measured. ROC analyses determined
      that the three obesity measurements were similar in predicting HTN and DM (AUC:
      0.6-0.7). The universal WC threshold of >= 35 in. missed 13% of the hypertensive
      patients and 12% of the diabetic patients. The Asian WC threshold of >= 31.5 in.
      increased detection of HTN and DM but with a high rate of false positives. The
      traditional BMI >= 25 kg/m2 threshold missed 35% of those with hypertension and
      24% of those with diabetes. The Asian BMI threshold improved detection but
      resulted in a high rate of false positives. The suggested WHtR cut-off of >= 0.5
      missed only 1% of those with HTN and 0% of those with DM. The three obesity
      measurements had similar but modest ability to predict HTN and DM in FAW. Using
      Asian-specific thresholds increased accuracy but with a high rate of false
      positives. Whether FAW, especially at older ages, should be encouraged to reach
      these lower thresholds needs further investigation because of the high false
      positive rates.

PMID- 27882292
TI  - Muscular strength and endurance and cardio-metabolic health in disadvantaged
      Hispanic children from the U.S.
AB  - The predictive relationship between muscular strength and endurance and cardio
      metabolic health, independent from aerobic fitness, is not clear in disadvantaged
      Hispanic children. The purpose of this study was to examine the predictive
      relationship between muscular strength and endurance and clustered cardio
      metabolic risk, controlling for aerobic fitness, in Hispanic children from low
      income schools. Participants were 320 Hispanic children (Mean age = 10.1 +/- 1.1
      years; 164 girls, 156 boys) recruited during the 2014-2015 and 2015-2016 academic
      years from five low-income schools from the state of Utah in the U.S. Muscular
      strength and endurance was assessed using the push-up and curl-up tests and
      estimated VO2 Peak was calculated from the Progressive Aerobic Cardiovascular
      Endurance Run. A clustered metabolic syndrome composite score (MetS) was
      calculated from cardio-metabolic health measurements consisting of HDL
      cholesterol, triglycerides, waist circumference, blood glucose, and mean arterial
      pressure (MAP). Multi-level general linear mixed effects models were used to
      examine the predictive relationship between muscular strength and endurance and
      MetS, controlling for the effect of aerobic fitness and the clustering of
      children within classrooms and schools. Children who were in the middle and upper
      tertiles for muscular strength and endurance associated with a lower (more
      favorable) MetS score (middle tertile: beta = - 2.59, 95% C.I. [- 4.23, - 0.95],
      p < 0.05; upper tertile: beta = - 1.57, 95% C.I. [- 3.20, - 0.16], p < 0.05). The
      results suggest that higher levels of muscular strength and endurance relate to
      lower cardio-metabolic risk, independent of aerobic fitness, in Hispanic children
      from low-income schools.

PMID- 27882293
TI  - Using mammograms to predict preventive health services behavior and mortality in
      women.
AB  - This study examined whether mammography receipt was associated with mortality due
      to causes other than breast cancer, hypothesizing that mammography screening was
      a proxy for the predisposition to seek preventive health behaviors. Using data on
      89,574 women from the 2000 National Health Interview Survey and National Death
      Index, a discrete-time hazard model estimated the mortality from any cause except
      breast cancer as a function of screening status. Receiving a mammogram was
      associated with a 24% reduction in the likelihood of death all causes except
      breast cancer. These odds were reduced to 21.1% when demographic and
      socioeconomic variables are added and reduced further to 20.9% when health
      resource variables were added. The final adjusted model shows that women who
      received a mammogram had reduced their probability of death by 20%. These results
      suggest women who undergo mammograms may be more likely to seek other preventive
      health services or engage in healthy behaviors that affect mortality. While the
      use of mammograms to predict breast cancer mortality merits further
      consideration, if a proxy for a woman's predisposition for additional preventive
      screenings, encouraging mammography may be a pivotal pathway for preventing
      mortality due to other causes for women.

PMID- 27882294
TI  - Cough and fever in an immigrant adolescent with abnormal chest X-ray.
AB  - Tuberculosis (TB) remains a leading cause of death from infectious disease
      worldwide with 80,000 pediatric deaths annually. Disease caused by Mycobacterium
      tuberculosis (Mtb) is usually asymptomatic in pediatric patients and resolves
      after completion of standard therapy with isoniazid (INH). Rare reports document
      children greater than 10 years of age in endemic regions developing adult type
      cavitary disease, an infectious pulmonary tuberculosis lesion. This is a notable
      case of post-infectious pulmonary TB disease with adult type cavitation in an
      immigrant adolescent, which developed even after completing standard therapy with
      INH. With increasing immigration of refugees from endemic regions into the United
      States, the Center for Disease Control implemented standardized testing and
      treatment of TB. However even with identification of disease, many immigrants may
      not seek treatment or complete therapy given lack of health insurance, and poor
      access to health care. This case of a 14 year old adolescent with post primary
      cavitary TB highlights the importance of directly observed therapy (DOT) and
      medication compliance. Perhaps as noteworthy, this case also emphasizes the need
      for pediatricians to recognize the impact on public health and the potential for
      spread of active TB within schools and the community especially in pulmonary
      cavitary lesion.

PMID- 27882295
TI  - Neuroanatomical correlates of childhood apraxia of speech: A connectomic
      approach.
AB  - Childhood apraxia of speech (CAS) is a paediatric speech sound disorder in which
      precision and consistency of speech movements are impaired. Most children with
      idiopathic CAS have normal structural brain MRI. We hypothesize that children
      with CAS have altered structural connectivity in speech/language networks
      compared to controls and that these altered connections are related to functional
      speech/language measures. Whole brain probabilistic tractography, using
      constrained spherical deconvolution, was performed for connectome generation in
      17 children with CAS and 10 age-matched controls. Fractional anisotropy (FA) was
      used as a measure of connectivity and the connections with altered FA between CAS
      and controls were identified. Further, the relationship between altered FA and
      speech/language scores was determined. Three intra-hemispheric/interhemispheric
      subnetworks showed reduction of FA in CAS compared to controls, including left
      inferior (opercular part) and superior (dorsolateral, medial and orbital part)
      frontal gyrus, left superior and middle temporal gyrus and left post-central
      gyrus (subnetwork 1); right supplementary motor area, left middle and inferior
      (orbital part) frontal gyrus, left precuneus and cuneus, right superior occipital
      gyrus and right cerebellum (subnetwork 2); right angular gyrus, right superior
      temporal gyrus and right inferior occipital gyrus (subnetwork 3). Reduced FA of
      some connections correlated with diadochokinesis, oromotor skills, expressive
      grammar and poor lexical production in CAS. These findings provide evidence of
      structural connectivity anomalies in children with CAS across specific brain
      regions involved in speech/language function. We propose altered connectivity as
      a possible epiphenomenon of complex pathogenic mechanisms in CAS which need
      further investigation.

PMID- 27882296
TI  - White matter abnormalities at a regional and voxel level in focal and generalized
      epilepsy: A systematic review and meta-analysis.
AB  - OBJECTIVE: Since the introduction of diffusion tensor imaging, white matter
      abnormalities in epilepsy have been studied extensively. However, the affected
      areas reported, the extent of abnormalities and the association with relevant
      clinical parameters are highly variable. We aimed to obtain a more consistent
      estimate of white matter abnormalities and their association with clinical
      parameters in different epilepsy types. METHODS: We systematically searched for
      differences in white matter fractional anisotropy and mean diffusivity, at
      regional and voxel level, between people with epilepsy and healthy controls. Meta
      analyses were used to quantify the directionality and extent of these
      differences. Correlations between white matter differences and age of epilepsy
      onset, duration of epilepsy and sex were assessed with meta-regressions. RESULTS:
      Forty-two studies, with 1027 people with epilepsy and 1122 controls, were
      included with regional data. Sixteen voxel-based studies were also included.
      People with temporal or frontal lobe epilepsy had significantly decreased
      fractional anisotropy (Delta -0.021, 95% confidence interval -0.026 to -0.016)
      and increased mean diffusivity (Delta0.026 * 10-3 mm2/s, 0.012 to 0.039) in the
      commissural, association and projection white matter fibers. White matter was
      much less affected in generalized epilepsy. White matter changes in people with
      focal epilepsy correlated with age at onset, epilepsy duration and sex.
      SIGNIFICANCE: This study provides a better estimation of white matter changes in
      different epilepsies. Effects are particularly found in people with focal
      epilepsy. Correlations with the duration of focal epilepsy support the hypothesis
      that these changes are, at least partly, a consequence of seizures and may
      warrant early surgery. Future studies need to guarantee adequate group sizes, as
      white matter differences in epilepsy are small.

PMID- 27882299
TI  - Application of target capture sequencing of exons and conserved non-coding
      sequences to 20 inbred rat strains.
AB  - We report sequence data obtained by our recently devised target capture method
      TargetEC applied to 20 inbred rat strains. This method encompasses not only all
      annotated exons but also highly conserved non-coding sequences shared among
      vertebrates. The total length of the target regions covers 146.8 Mb. On an
      average, we obtained 31.7 * depth of target coverage and identified 154,330 SNVs
      and 24,368 INDELs for each strain. This corresponds to 470,037 unique SNVs and
      68,652 unique INDELs among the 20 strains. The sequence data can be accessed at
      DDBJ/EMBL/GenBank under accession number PRJDB4648, and the identified variants
      have been deposited at http://bioinfo.sls.kyushu
      u.ac.jp/rat_target_capture/20_strains.vcf.gz.

PMID- 27882297
TI  - Disrupted functional connectivity affects resting state based language
      lateralization.
AB  - Pre-operative assessment of language localization and lateralization is critical
      to preserving brain function after lesion or epileptogenic tissue resection. Task
      fMRI (t-fMRI) has been extensively and reliably used to this end, but resting
      state fMRI (rs-fMRI) is emerging as an alternative pre-operative brain mapping
      method that is independent of a patient's ability to comply with a task. We
      sought to evaluate if language lateralization obtained from rs-fMRI can replace
      standard assessment using t-fMRI. In a group of 43 patients scheduled for pre
      operative fMRI brain mapping and 17 healthy controls, we found that existing
      methods of determining rs-fMRI lateralization by considering interhemispheric and
      intrahemispheric functional connectivity are inadequate compared to t-fMRI when
      applied to the language network. We determined that this was attributable to
      widespread but nuanced disturbances in the functional connectivity of the
      language network in patients. We found changes in interhemispheric and
      intrahemispheric functional connectivity that were dependent on lesion location,
      and particularly impacted patients with lesions in the left temporal lobe. We
      then tested whether a simpler measure of functional connectivity to the language
      network has a better relation to t-fMRI based language lateralization.
      Remarkably, we found that functional connectivity between the language network
      and the frontal pole, and superior frontal gyrus, as well as the supramarginal
      gyrus, significantly correlated to task based language lateralization indices in
      both patients and healthy controls. These findings are consistent with prior work
      with epilepsy patients, and provide a framework for evaluating language
      lateralization at rest.

PMID- 27882300
TI  - No light at the end of the tunnel... an unfortunate case of varicella-associated
      progressive outer retinal necrosis in a patient with neglected HIV infection.

PMID- 27882302
TI  - Pyonephrosis and pyocystis.

PMID- 27882298
TI  - High frequency oscillations and high frequency functional network characteristics
      in the intraoperative electrocorticogram in epilepsy.
AB  - OBJECTIVE: High frequency oscillations (HFOs; > 80 Hz), especially fast ripples
      (FRs, 250-500 Hz), are novel biomarkers for epileptogenic tissue. The
      pathophysiology suggests enhanced functional connectivity within FR generating
      tissue. Our aim was to determine the relation between brain areas showing FRs and
      'baseline' functional connectivity within EEG networks, especially in the high
      frequency bands. METHODS: We marked FRs, ripples (80-250 Hz) and spikes in the
      electrocorticogram of 14 patients with refractory temporal lobe epilepsy. We
      assessed 'baseline' functional connectivity in epochs free of epileptiform events
      within these recordings, using the phase lag index. We computed the Eigenvector
      Centrality (EC) per channel in the FR and gamma band network. We compared EC
      between channels that did or did not show events at other moments in time.
      RESULTS: FR-band EC was higher in channels with than without spikes. Gamma-band
      EC was lower in channels with ripples and FRs. CONCLUSIONS: We confirmed previous
      findings of functional isolation in the gamma-band and found a first proof of
      functional integration in the FR-band network of channels covering presumed
      epileptogenic tissue. SIGNIFICANCE: 'Baseline' high-frequency network parameters
      might help intra-operative recognition of epileptogenic tissue without the need
      for waiting for events. These findings can increase our understanding of the
      'architecture' of epileptogenic networks and help unravel the pathophysiology of
      HFOs.

PMID- 27882301
TI  - Prolonged shedding of Chikungunya virus in semen and urine: A new perspective for
      diagnosis and implications for transmission.
AB  - We report the presence of Chikungunya (CHIKV) RNA in the blood, urine and semen
      during the acute phase of the disease in an adult with a dual infection with
      Dengue virus type 3. The patient, a 25 yr-old man from Salvador, Brazil, reported
      a 6-day duration of high fever, arthralgia, myalgia, headache and
      photophobia.Blood and semen specimens were positive for CHIKV in the first
      collected samples; semen and urine specimens were positive for CHIKV after 30
      days of symptoms onset. DENV-3 RNA was positive in blood specimen when first
      collected 6 days after the initiation of symptoms.We describe for the first time
      the presence of CHIKV RNA in urine and semen for an extended period of time and
      we address the possible implications of these findings for diagnosis and
      transmission dynamics.

PMID- 27882303
TI  - Ovarian-like differentiation in eutopic and ectopic endometrioses with aberrant
      FSH receptor, INSL3 and GATA4/6 expression.
AB  - Endometriosis, the hormone-dependent extrauterine dissemination of endometrial
      tissue outside the uterus, affects 5-15% of women of reproductive age.
      Pathogenesis remains poorly understood as well as the estrogen production by
      endometriotic tissue yielding autocrine growth. Estrogens (E2) are normally
      produced by the ovaries. We investigated whether aberrant "ovarian-like"
      differentiation occurred in endometriosis. 69 women, with (n = 38) and without (n
      = 31) histologically proven endometriosis were recruited. Comparative RT-qPCR was
      performed on 20 genes in paired eutopic and ectopic lesions, together with
      immunohistochemistry. Functional studies were performed in primary cultures of
      epithelial endometriotic cells (EEC). A broaden ovarian-like differentiation was
      found in half eutopic and all ectopic endometriosis with aberrant expression of
      transcripts and protein for the transcription factors GATA4 and GATA6 triggering
      ovarian differentiation, for the FSH receptor (FSHR) and the ovarian hormone
      INSL3. Like in ovaries the FSHR induced aromatase, the key enzyme in E2
      production, and vascular factors in EEC. The LH receptor (LHR) was also
      aberrantly expressed in a subset of ectopic endometriosis (21%) and induced
      strongly androgen-synthesizing enzymes and INSL3 in EEC, as in ovaries, as well
      as endometriotic cell growth. The ERK pathway mediates signaling by both
      hormones. A positive feedback loop occurred through FSHR and LHR-dependent
      induction of GATA4/6 in EEC, as in ovaries, enhancing the production of the
      steroidogenic cascade. This work highlights a novel pathophysiological mechanism
      with a broadly ovarian pattern of differentiation in half eutopic and all ectopic
      endometriosis. This study provides new tools that might improve the diagnosis of
      endometriosis in the future.

PMID- 27882304
TI  - Metabolic and adaptive immune responses induced in mice infected with tissue
      dwelling nematode Trichinella zimbabwensis.
AB  - Tissue-dwelling helminths are known to induce intestinal and systemic
      inflammation accompanied with host compensatory mechanisms to counter balance
      nutritional and metabolic deficiencies. The metabolic and immune responses of the
      host depend on parasite species and tissues affected by the parasite. This study
      investigated metabolic and immuno-inflammatory responses of mice infected with
      tissue-dwelling larvae of Trichinella zimbabwensis and explored the relationship
      between infection, metabolic parameters and Th1/Th17 immune responses. Sixty (60)
      female BALB/c mice aged between 6 to 8 weeks old were randomly assigned into T.
      zimbabwensis-infected and control groups. Levels of Th1 (interferon-gamma) and
      Th17 (interleukin-17) cytokines, insulin and blood glucose were determined as
      well as measurements of body weight, food and water intake. Results showed that
      during the enteric phase of infection, insulin and IFN-gamma levels were
      significantly higher in the Trichinella infected group accompanied with a
      reduction in the trends of food intake and weight loss compared with the control
      group. During systemic larval migration, trends in food and water intake were
      significantly altered and this was attributed to compensatory feeding resulting
      in weight gain, reduced insulin levels and increased IL-17 levels. Larval
      migration also induced a Th1/Th17 derived inflammatory response. It was concluded
      that T. zimbabwensis alters metabolic parameters by instigating host compensatory
      feeding. Furthermore, we showed for the first time that non-encapsulated T.
      zimbabwensis parasite plays a role in immunomodulating host Th1/Th17 type
      responses during chronic infection.

PMID- 27882305
TI  - Splenophrenic portosystemic shunt in dogs with and without portal hypertension:
      can acquired and congenital porto-caval connections coexist?
AB  - The possible existence of the same pattern of porto-caval connection in dogs
      having a single congenital portosystemic shunt (CPSS) and in dogs having multiple
      acquired portosystemic shunt (MAPSS) secondary to portal hypertension (PH) was
      evaluated. Retrospective evaluation of all CT examinations of patients having
      portosystemic shunt (PSS) was performed in a 4-year time period. All anomalous
      porto-caval connections were assessed for anatomical pattern and compared with
      published veterinary literature. Records of 25 dogs were reviewed. 16 dogs had a
      single CPSS (CPSS group), and 9 dogs had multiple acquired PSS secondary to PH
      (APSS group). The splenophrenic shunt pattern was found in 3 dogs of the CPSS
      group as a single congenital anomaly without PH and in 2 dogs of the APSS group
      associated with MAPSS and ascites due to different hepatic diseases causing PH.
      These findings corroborate two hypotheses: 1) Splenophrenic PSS should be
      considered as a classical CPSS but if this is not sufficient to alleviate a PH
      developed after birth because of eventual hepatic or portal diseases, in this
      case ascites and acquired portal collaterals may develop. In this case, MAPSS and
      CPSS may coexist. 2) The pattern of splenophrenic PSS, classically described
      among CPSS, may develop as acquired portal collateral in dogs with PH and it
      should also be included in the category of APSS. These preliminary findings may
      be helpful in reconsidering the classical haemodynamics of porto-caval diseases,
      enrich the classification of APSS in dogs and refine the imaging evaluation of
      patients with PH.

PMID- 27882307
TI  - Metabolic Imaging in Prostate Cancer: Where We Are.
AB  - In recent years, the development of diagnostic methods based on metabolic imaging
      has been aimed at improving diagnosis of prostate cancer (PCa) and perhaps at
      improving therapy. Molecular imaging methods can detect specific biological
      processes that are different when detected within cancer cells relative to those
      taking place in surrounding normal tissues. Many methods are sensitive to tissue
      metabolism; among them, positron emission tomography (PET) and magnetic resonance
      spectroscopic imaging (MRSI) are widely used in clinical practice and clinical
      research. There is a rich literature that establishes the role of these metabolic
      imaging techniques as valid tools for the diagnosis, staging, and monitoring of
      PCa. Until recently, European guidelines for PCa detection still considered both
      MRSI/MRI and PET/CT to be under evaluation, even though they had demonstrated
      their value in the staging of high risk PCa, and in the restaging of patients
      presenting elevated prostatic-specific antigen levels following radical treatment
      of PCa, respectively. Very recently, advanced methods for metabolic imaging have
      been proposed in the literature: multiparametric MRI (mpMRI), hyperpolarized
      MRSI, PET/CT with the use of new tracers and finally PET/MRI. Their detection
      capabilities are currently under evaluation, as is the feasibility of using such
      techniques in clinical studies.

PMID- 27882308
TI  - Prognostic Impact of Autophagy Biomarkers for Cutaneous Melanoma.
AB  - Prognosis and survival for malignant melanoma is highly dependent on early
      diagnosis and treatment. While the American Joint Committee on Cancer (AJCC)
      criterion provides a means of staging melanomas and guiding treatment approaches,
      it is unable to identify the risk of disease progression of early stage tumors or
      provide reliable stratification for novel adjuvant therapies. The demand for
      credible prognostic/companion biomarkers able to identify high-risk melanoma
      subgroups as well as guide more effective personalized/precision-based therapy is
      therefore of paramount importance. Autophagy, the principle lysosomal-mediated
      process for the degradation/recycling of cellular debris, is a hot topic in
      cancer medicine, and observations of its deregulation in melanoma have brought
      its potential as a prognostic biomarker to the forefront of current research. Key
      regulatory proteins, including Atg8/microtubule-associated light chain 3 (LC3)
      and BECN1 (Beclin 1), have been proposed as potential prognostic biomarkers.
      However, given the dynamic nature of autophagy, their expression in vitro does
      not translate to their use as a prognostic biomarker for melanoma in vivo. We
      have recently identified the expression levels of Sequestosome1/SQSTM1 (p62) and
      activating molecule in Beclin 1-regulated autophagy protein 1 (AMBRA1) as novel
      independent prognostic biomarkers for early stage melanomas. While increasing
      followed by subsequent decreasing levels of p62 expression reflects the
      paradoxical role of autophagy in melanoma, expression levels additionally define
      a novel prognostic biomarker for AJCC stage II tumors. Conversely, loss of AMBRA1
      in the epidermis overlying primary melanomas defines a novel prognostic biomarker
      for AJCC stage I tumors. Collectively, the definition of AMBRA1 and p62 as
      prognostic biomarkers for early stage melanomas provides novel and accurate means
      through which to identify tumors at risk of disease progression, facilitating
      earlier patient therapeutic intervention and stratification tools for novel
      personalized therapeutic approaches to improve clinical outcome.

PMID- 27882309
TI  - Enhanced fold recognition using efficient short fragment clustering.
AB  - The main structure aligner in the CCP4 Software Suite, SSM (Secondary Structure
      Matching) has a limited applicability on the intermediate stages of the structure
      solution process, when the secondary structure cannot be reliably computed due to
      structural incompleteness or a fragmented mainchain. In this study, we describe a
      new algorithm for the alignment and comparison of protein structures in CCP4,
      which was designed to overcome SSM's limitations but retain its quality and
      speed. The new algorithm, named GESAMT (General Efficient Structural Alignment of
      Macromolecular Targets), employs the old idea of deriving the global structure
      similarity from a promising set of locally similar short fragments, but uses a
      few technical solutions that make it considerably faster. A comparative
      sensitivity and selectivity analysis revealed an unexpected significant
      improvement in the fold recognition properties of the new algorithm, which also
      makes it useful for applications in the structural bioinformatics domain. The new
      tool is included in the CCP4 Software Suite starting from version 6.3.

PMID- 27882306
TI  - Personalized Proteomics: The Future of Precision Medicine.
AB  - Medical diagnostics and treatment has advanced from a one size fits all science
      to treatment of the patient as a unique individual. Currently, this is limited
      solely to genetic analysis. However, epigenetic, transcriptional, proteomic,
      posttranslational modifications, metabolic, and environmental factors influence a
      patient's response to disease and treatment. As more analytical and diagnostic
      techniques are incorporated into medical practice, the personalized medicine
      initiative transitions to precision medicine giving a holistic view of the
      patient's condition. The high accuracy and sensitivity of mass spectrometric
      analysis of proteomes is well suited for the incorporation of proteomics into
      precision medicine. This review begins with an overview of the advance to
      precision medicine and the current state of the art in technology and
      instrumentation for mass spectrometry analysis. Thereafter, it focuses on the
      benefits and potential uses for personalized proteomic analysis in the diagnostic
      and treatment of individual patients. In conclusion, it calls for a synthesis
      between basic science and clinical researchers with practicing clinicians to
      design proteomic studies to generate meaningful and applicable translational
      medicine. As clinical proteomics is just beginning to come out of its infancy,
      this overview is provided for the new initiate.

PMID- 27882310
TI  - Minimal invasive horizontal ridge augmentation using subperiosteal tunneling
      technique.
AB  - BACKGROUND: The goal of this study was to retrospectively evaluate the prognosis
      of minimal invasive horizontal ridge augmentation (MIHRA) technique using small
      incision and subperiosteal tunneling technique. METHODS: This study targeted 25
      partially edentulous patients (10 males and 15 females, mean age 48.8 +/- 19.7
      years) who needed bone graft for installation of the implants due to alveolar
      bone deficiency. The patients took the radiographic exam, panoramic and
      periapical view at first visit, and had implant fixture installation surgery. All
      patients received immediate or delayed implant surgery with bone graft using U
      shaped incision and tunneling technique. After an average of 2.8 months, the
      prosthesis was connected and functioned. The clinical prognosis was recorded by
      observation of the peri-implant tissue at every visit. A year after restoration,
      the crestal bone loss around the implant was measured by taking the follow-up
      radiographs. One patient took 3D-CT before bone graft, after bone graft, and 2
      years after restoration to compare and analyze change of alveolar bone width.
      RESULTS: This study included 25 patients and 39 implants. Thirty eight implants
      (97.4 %) survived. As for postoperative complications, five patients showed minor
      infection symptoms, like swelling and tenderness after bone graft. The other one
      had buccal fenestration, and secondary bone graft was done by the same technique.
      No complications related with bone graft were found except in these patients. The
      mean crestal bone loss around the implants was 0.03 mm 1 year after restoration,
      and this was an adequate clinical prognosis. A patient took 3D-CT after bone
      graft, and the width of alveolar bone increased 4.32 mm added to 4.6 mm of former
      alveolar bone width. Two years after bone graft, the width of alveolar bone was
      8.13 mm, and this suggested that the resorption rate of bone graft material was
      18.29 % during 2 years. CONCLUSIONS: The bone graft material retained within a
      pouch formed using U-shaped incision and tunneling technique resulted with a few
      complications, and the prognosis of the implants placed above the alveolar bone
      was adequate.

PMID- 27882311
TI  - Retrospective clinical study of an implant with a sandblasted, large-grit, acid
      etched surface and internal connection: analysis of short-term success rate and
      marginal bone loss.
AB  - BACKGROUND: The purpose of this retrospective study was to evaluate the clinical
      utility of an implant with a sandblasted, large-grit, acid-etched (SLA) surface
      and internal connection. METHODS: Six patients who received dental implants in
      the Department of Oral and Maxillofacial Surgery, Chonnam National University
      Dental Hospital, were analyzed by factors influencing the success rate and
      marginal bone loss. Factors included patient's age, sex, implant installation
      site, whether bone graft was done, type of bone graft materials, approaching
      method if sinus lift was done, and the size of the fixture. In addition, the
      marginal bone loss was analyzed by using a radiograph. RESULTS: All implants were
      successful, and the cumulative survival rate was 100 %. Average marginal bone
      loss of 6 months after the installation was 0.52 mm and 20 months after the
      functional loading was 1.06 mm. Total marginal bone resorption was 1.58 mm on
      average. There was no statistically significant difference in mesial and distal
      marginal bone loss. CONCLUSIONS: The short-term clinical success rate of the
      implant with an SLA surface and internal connection was satisfactory. Moreover,
      the marginal bone loss was also consistent with the implant success criteria.

PMID- 27882312
TI  - Supernumerary nostril: a case report.
AB  - BACKGROUND: Supernumerary nostril is a congenital anomaly that contains
      additional nostril with or without accessory cartilage. These rare congenital
      nasal deformities result from embryological defects. Since 1906, Lindsay (Trans
      Pathol Soc Lond. 57:329-330, 1906) has published the first research of bilateral
      supernumerary nostrils, and only 34 cases have been reported so far in the
      English literature. CASE PRESENTATION: A 1-year-old female baby was brought to
      our department group for the treatment of an accessory opening above the left
      nostril which had been presented since her birth. Medical history was non
      specific and her birth was normal. The size of a supernumerary nostril was about
      0.2 cm diameter and connected to the left nostril. The right one was normal.
      Minimal procedure was operated for the anomaly. After 1 year, rhinoplasty was
      performed for the nostril asymmetry. CONCLUSIONS: At 1 year follow-up, the
      functional and cosmetic result was satisfactory. In this case, it is important
      that we have early preoperative diagnosis. Also, it is desirable that we should
      perform a corrective surgery as soon as possible for the patient's psychosocial
      growth.

PMID- 27882313
TI  - Experiences in Tick Control by Acaricide in the Traditional Cattle Sector in
      Zambia and Burkina Faso: Possible Environmental and Public Health Implications.
AB  - Livestock, especially cattle, play a paramount role in agriculture production
      systems, particularly in poor countries throughout the world. Ticks and tick
      borne diseases (TBDs) have an important impact on livestock and agriculture
      production in sub-Saharan Africa. The authors review the most common methods used
      for the control of ticks and TBDs. Special emphasis is given to the direct
      application of acaricides to the host animals. The possible environmental and
      public health adverse effects (i.e., risks for the workers, residues in the
      environment and in food products of animal origin) are mentioned. The authors
      present two case studies, describing different field experiences in controlling
      ticks in two African countries. In Zambia (Southern Africa), a strategic dipping
      regime was used to control Rhipicephalus appendiculatus ticks, vectors of
      theileriosis, a deadly disease affecting cattle in the traditional livestock
      sector in Southern Province. The dipping regime adopted allowed to reduce the
      tick challenge and cattle mortally rate and, at the same time, to employ less
      acaricide as compared to the intensive dipping used so far, without disrupting
      the building-up of enzootic stability. In Burkina Faso (West Africa), where
      dipping was never used for tick control, an acaricide footbath was employed as an
      alternative method to the traditional technique used locally (portable manual
      sprayers). This was developed from field observations on the invasion/attachment
      process of the Amblyomma variegatum ticks - vector of cowdriosis - on the animal
      hosts, leading to a control method aimed to kill ticks temporarily attached to
      the interdigital areas before their permanent attachment to the predilection
      sites. This innovative method has been overall accepted by the local farmers. It
      has the advantage of greatly reducing costs of treatments and has a minimal
      environmental impact, making footbath a sustainable and replicable method,
      adoptable also in other West African countries. Although the two methods
      described, developed in very different contexts, are not comparable - if public
      health and environmental implications are taken into account, if a balance among
      efficacy of the control method(s), cost-effectiveness and sustainability is
      reached - a way forward for the implementation of a One Health strategy can be
      set.

PMID- 27882314
TI  - The Role of Pharmacists in Preventing Falls among America's Older Adults.
AB  - Falls are the leading cause of both fatal and non-fatal injuries in people aged
      65 years and older and can lead to significant costs, injuries, functional
      decline, and reduced quality of life. While certain medications are known to
      increase fall risk, medication use is a modifiable risk factor. Pharmacists have
      specialized training in medication management and can play an important role in
      fall prevention. Working in a patient-centered team-based approach, pharmacists
      can collaborate with the primary care providers to reduce fall risk. They can
      screen for fall risk, review and optimize medication therapy, recommend vitamin
      D, and educate patients and caregivers about ways to prevent falls. To help
      health-care providers implement fall prevention, the Centers for Disease Control
      and Prevention developed the Stopping Elderly Accidents, Deaths, and Injuries
      (STEADI) initiative. Based on the established clinical guidelines, STEADI
      provides members of the health-care team, including pharmacists, with the tools
      and resources they need to manage their older patients' fall risk. These tools
      are being adapted to specifically advance the roles of pharmacists in reviewing
      medications, identifying those that increase fall risk, and communicating those
      risks with patients' primary care providers. Through a multidisciplinary
      approach, pharmacists along with other members of the health-care team can better
      meet the needs of America's growing older adult population and reduce falls.

PMID- 27882316
TI  - A lncRNA Perspective into (Re)Building the Heart.
AB  - Our conception of the human genome, long focused on the 2% that codes for
      proteins, has profoundly changed since its first draft assembly in 2001. Since
      then, an unanticipatedly expansive functionality and convolution has been
      attributed to the majority of the genome that is transcribed in a cell
      type/context-specific manner into transcripts with no apparent protein coding
      ability. While the majority of these transcripts, currently annotated as long non
      coding RNAs (lncRNAs), are functionally uncharacterized, their prominent role in
      embryonic development and tissue homeostasis, especially in the context of the
      heart, is emerging. In this review, we summarize and discuss the latest advances
      in understanding the relevance of lncRNAs in (re)building the heart.

PMID- 27882318
TI  - Sialendoscopy and Combined Minimally Invasive Treatment for Large Parotid Stones.
AB  - Sialendoscopy (SE) represents nowadays one of the standard diagnostic and
      therapeutic procedures in the treatment of major salivary glands lithiasis. We
      know from experience that it is successful only in small percentage of patients,
      when used in monotherapy. However, it represents an indispensable part of all of
      the combined minimally invasive gland-preserving treatment techniques, the
      success rate of which is around 90%. In this work, we focused on the role of
      sialendoscopy in the treatment of patients with larger inflamed fixed stones in
      glandula parotis. We conducted a total of 364 sialendoscopy procedures in 332
      patients on our site. We have confirmed lithiasis as a cause of salivary gland
      obstruction in 246 (74%) patients. In 9 patients there was larger, single, or
      multiple inflamed fixed lithiasis of glandula parotis. In this subgroup of
      patients endoscopically assisted sialolithectomy from external mini-incision has
      become the method of choice. In 9 of the 9 (100%) cases we have achieved complete
      elimination of stones, and in 8 of the 9 (89%) cases we have achieved complete
      elimination of complaints. Sialoendoscopically assisted sialolithectomy of
      glandula parotis from external mini-incision has proved to be highly effective
      technique to eliminate stones with minimal complications.

PMID- 27882319
TI  - The Impact of Endometriosis on the Health of Women 2016.

PMID- 27882317
TI  - Bacterial RNA Polymerase-DNA Interaction-The Driving Force of Gene Expression and
      the Target for Drug Action.
AB  - DNA-dependent multisubunit RNA polymerase (RNAP) is the key enzyme of gene
      expression and a target of regulation in all kingdoms of life. It is a complex
      multifunctional molecular machine which, unlike other DNA-binding proteins,
      engages in extensive and dynamic interactions (both specific and nonspecific)
      with DNA, and maintains them over a distance. These interactions are controlled
      by DNA sequences, DNA topology, and a host of regulatory factors. Here, we
      summarize key recent structural and biochemical studies that elucidate the fine
      details of RNAP-DNA interactions during initiation. The findings of these studies
      help unravel the molecular mechanisms of promoter recognition and open complex
      formation, initiation of transcript synthesis and promoter escape. We also
      discuss most current advances in the studies of drugs that specifically target
      RNAP-DNA interactions during transcription initiation and elongation.

PMID- 27882315
TI  - Septin Mutations in Human Cancers.
AB  - Septins are GTP-binding proteins that are evolutionarily and structurally related
      to the RAS oncogenes. Septin expression levels are altered in many cancers and
      new advances point to how abnormal septin expression may contribute to the
      progression of cancer. In contrast to the RAS GTPases, which are frequently
      mutated and actively promote tumorigenesis, little is known about the occurrence
      and role of septin mutations in human cancers. Here, we review septin missense
      mutations that are currently in the Catalog of Somatic Mutations in Cancer
      (COSMIC) database. The majority of septin mutations occur in tumors of the large
      intestine, skin, endometrium and stomach. Over 25% of the annotated mutations in
      SEPT2, SEPT4, and SEPT9 belong to large intestine tumors. From all septins, SEPT9
      and SEPT14 exhibit the highest mutation frequencies in skin, stomach and large
      intestine cancers. While septin mutations occur with frequencies lower than 3%,
      recurring mutations in several invariant and highly conserved amino acids are
      found across different septin paralogs and tumor types. Interestingly, a
      significant number of these mutations occur in the GTP-binding pocket and septin
      dimerization interfaces. Future studies may determine how these somatic mutations
      affect septin structure and function, whether they contribute to the progression
      of specific cancers and if they could serve as tumor-specific biomarkers.

PMID- 27882320
TI  - MediterrAsian Diet Products That Could Raise HDL-Cholesterol: A Systematic
      Review.
AB  - Background. High HDL-cholesterol (HDL-C) values are negatively correlated with
      cardiovascular diseases. This review analyses the effect of the supplementation
      with various Mediterranean diet products (artichoke, bergamot, and olive oil) and
      Asian diet products (red yeast rice) on the HDL-C value in dyslipidemic subjects.
      Methods. A systematic review has been done involving all the English written
      studies published from the 1st of January 1958 to the 31st of March 2016.
      Results. The results of this systematic review indicate that the dietary
      supplementation with red yeast rice, bergamot, artichoke, and virgin olive oil
      has promising effects on the increase of HDL-C serum levels. The artichoke leaf
      extract and virgin olive oil appear to be particularly interesting, while
      bergamot extract needs further research and the effect of red yeast rice seems to
      be limited to patients with previous myocardial infarction. Conclusions. Various
      MediterrAsian diet products or natural extracts may represent a potential
      intervention treatment to raise HDL-C in dyslipidemic subjects.

PMID- 27882321
TI  - MicroRNAs in Coronary Heart Disease: Ready to Enter the Clinical Arena?
AB  - Coronary artery disease (CAD) and its complication remain the leading cause of
      mortality in industrialized countries despite great advances in terms of
      diagnosis, prognosis, and treatment options. MicroRNAs (miRNAs), small noncoding
      RNAs, act as posttranscriptional gene expression modulators and have been
      implicated as key regulators in several physiological and pathological processes
      linked to CAD. Circulating miRNAs have been evaluated as promising novel
      biomarkers of CAD, acute coronary syndromes, and acute myocardial infarction,
      with prognostic implications. Several challenges related to technical aspects,
      miRNAs normalization, drugs interaction, and quality reporting of statistical
      multivariable analysis of the miRNAs observational studies remain unresolved.
      MicroRNA-based therapies in cardiovascular diseases are not ready yet for human
      trials but definitely appealing. Through this review we will provide clinicians
      with a concise overview of the pros and cons of microRNAs.

PMID- 27882323
TI  - Effect of Methionine Restriction on Bone Density and NK Cell Activity.
AB  - Methionine restriction (MR) is proven to increase the lifespan; and it also
      affects the bone density and the innate immune system. The aim of this study is
      to explore the effect of methionine restriction on bone density and natural
      killer (NK) cells. C57BL/6J mice were subjected to either basal diet (BD,
      containing 0.80% methionine) or methionine-restricted diet (containing 0.14%
      methionine). Mice with MR diet displayed reduced bone mass and decrease in the
      cytotoxicity of NK from the spleen, compared to BD animals. Also, mice with MR
      diet had an inferior body weight (P < 0.05) and higher plasma levels of
      adiponectin and FGF21 (P < 0.05) but lower concentrations of leptin and IGF-1 (P
      < 0.05). Overall, the investigation shows that methionine affects bone density
      and NK cell cytotoxicity.

PMID- 27882322
TI  - Identification of Species of Nontuberculous Mycobacteria Clinical Isolates from 8
      Provinces of China.
AB  - Pulmonary diseases caused by nontuberculous mycobacteria (NTM) are increasing in
      incidence and prevalence worldwide. In this study, we identified NTM species of
      the clinical isolates from 8 provinces in China, in order to preliminarily
      provide some basic scientific data in the different species and distribution of
      NTM related to pulmonary disease in China. A total of 523 clinical isolates from
      patients with tuberculosis (TB) diagnosed clinically from 2005 to 2012 were
      identified to the species using conventional and molecular methods, including
      multilocus PCR, rpoB and hsp65 PCR-PRA, hsp65, rpoB, and 16S-23S internal
      transcribed spacer region sequencing. The isolates were identified into 3
      bacterium genera, including NTM, Gordonia bronchialis, and Nocardia farcinica,
      and, for the 488 NTM isolates, 27 species were identified. For all the 27 species
      of NTM which were found to cause pulmonary infections in humans, the most
      prevalent species was M. intracellulare, followed by M. avium and M. abscessus.
      And seven other species were for the first time identified in patients with TB in
      China. NTM species identification is very important for distinguishing between
      tuberculosis and NTM pulmonary diseases, and the species diversity drives the
      creation of diverse and integrated identification methods with higher accuracy
      and efficacy.

PMID- 27882324
TI  - Studies on the Ecological Adaptability of Growing Rice with Floating Bed on the
      Dilute Biogas Slurry.
AB  - This study aimed to explore the ecological adaptability and the possibility of
      growing rice with floating bed on the dilute biogas slurry. The results of the
      experiments show that the growth stage, rice plant height, and rice yield and
      quality were significantly affected by multiple dilutions; rice plants cultivated
      with 45 multiple dilutions had better ecological adaptability than others. In the
      45 multiple dilutions' group, the yield of rice was 13.3 g/bucket (8 rice
      plants), milled rice rate was 63.1%, and the content of crude protein in the rice
      was 6.3%. The concentrations of heavy metals in the rice cultivated with 30
      multiple dilutions' slurry, such as total lead, cadmium, mercury, chromium, and
      arsenic, were all below the national standard. The study shows that it is
      possible and safe to cultivate rice plants with no soil but diluted biogas
      slurry. In the experiments, the yield, milled rice rate, and crude protein of the
      rice cultivated with slurry were not as much as those of rice cultivated with
      regular way in soil. This study provides the basic theoretical support for the
      development of biogas projects and the potential achievement of organic farming
      in special agricultural facilities and circular economy.

PMID- 27882325
TI  - Identification of Hot Spots in Protein Structures Using Gaussian Network Model
      and Gaussian Naive Bayes.
AB  - Residue fluctuations in protein structures have been shown to be highly
      associated with various protein functions. Gaussian network model (GNM), a simple
      representative coarse-grained model, was widely adopted to reveal function
      related protein dynamics. We directly utilized the high frequency modes generated
      by GNM and further performed Gaussian Naive Bayes (GNB) to identify hot spot
      residues. Two coding schemes about the feature vectors were implemented with
      varying distance cutoffs for GNM and sliding window sizes for GNB based on
      tenfold cross validations: one by using only a single high mode and the other by
      combining multiple modes with the highest frequency. Our proposed methods
      outperformed the previous work that did not directly utilize the high frequency
      modes generated by GNM, with regard to overall performance evaluated using F1
      measure. Moreover, we found that inclusion of more high frequency modes for a GNB
      classifier can significantly improve the sensitivity. The present study provided
      additional valuable insights into the relation between the hot spots and the
      residue fluctuations.

PMID- 27882326
TI  - Ventricular Fibrillation-Induced Cardiac Arrest Results in Regional Cardiac
      Injury Preferentially in Left Anterior Descending Coronary Artery Territory in
      Piglet Model.
AB  - Objective. Decreased cardiac function after resuscitation from cardiac arrest
      (CA) results from global ischemia of the myocardium. In the evolution of
      postarrest myocardial dysfunction, preferential involvement of any coronary
      arterial territory is not known. We hypothesized that there is no preferential
      involvement of any coronary artery during electrical induced ventricular
      fibrillation (VF) in piglet model. Design. Prospective, randomized controlled
      study. Methods. 12 piglets were randomized to baseline and electrical induced VF.
      After 5 min, the animals were resuscitated according to AHA PALS guidelines.
      After return of spontaneous circulation (ROSC), animals were observed for an
      additional 4 hours prior to cardiac MRI. Data (mean +/- SD) was analyzed using
      unpaired t-test; p value <= 0.05 was considered statistically significant.
      Results. Segmental wall motion (mm; baseline versus postarrest group) in segment
      7 (left anterior descending (LAD)) was 4.68 +/- 0.54 versus 3.31 +/- 0.64, p =
      0.0026. In segment 13, it was 3.82 +/- 0.96 versus 2.58 +/- 0.82, p = 0.02. In
      segment 14, it was 2.42 +/- 0.44 versus 1.29 +/- 0.99, p = 0.028. Conclusion.
      Postarrest myocardial dysfunction resulted in segmental wall motion defects in
      the LAD territory. There were no perfusion defects in the involved segments.

PMID- 27882327
TI  - Migration of BTEX and Biodegradation in Shallow Underground Water through Fuel
      Leak Simulation.
AB  - To provide more reasonable references for remedying underground water, fuel leak
      was simulated by establishing an experimental model of a porous-aquifer sand tank
      with the same size as that of the actual tank and by monitoring the underground
      water. In the tank, traditional gasoline and ethyl alcohol gasoline were poured.
      This study was conducted to achieve better understanding of the migration and
      distribution of benzene, toluene, ethyl benzene, and xylene (BTEX), which are
      major pollutants in the underground water. Experimental results showed that,
      compared with conventional gasoline, the content peak of BTEX in the mixture of
      ethyl alcohol gasoline appeared later; BTEX migrated along the water flow
      direction horizontally and presented different pollution halos; BTEX also
      exhibited the highest content level at 45 cm depth; however, its content declined
      at the 30 and 15 cm depths vertically because of the vertical dispersion effect;
      the rise of underground water level increased the BTEX content, and the
      attenuation of BTEX content in underground water was related to the
      biodegradation in the sand tank, which mainly included biodegradation with
      oxygen, nitrate, and sulfate.

PMID- 27882328
TI  - Genomic Analysis of a Marine Bacterium: Bioinformatics for Comparison,
      Evaluation, and Interpretation of DNA Sequences.
AB  - A total of five highly related strains of an unidentified marine bacterium were
      analyzed through their short genome sequences (AM260709-AM260713). Genome-to
      Genome Distance (GGDC) showed high similarity to Pseudoalteromonas haloplanktis
      (X67024). The generated unique Quick Response (QR) codes indicated no identity to
      other microbial species or gene sequences. Chaos Game Representation (CGR) showed
      the number of bases concentrated in the area. Guanine residues were highest in
      number followed by cytosine. Frequency of Chaos Game Representation (FCGR)
      indicated that CC and GG blocks have higher frequency in the sequence from the
      evaluated marine bacterium strains. Maximum GC content for the marine bacterium
      strains ranged 53-54%. The use of QR codes, CGR, FCGR, and GC dataset helped in
      identifying and interpreting short genome sequences from specific isolates. A
      phylogenetic tree was constructed with the bootstrap test (1000 replicates) using
      MEGA6 software. Principal Component Analysis (PCA) was carried out using EMBL-EBI
      MUSCLE program. Thus, generated genomic data are of great assistance for
      hierarchical classification in Bacterial Systematics which combined with
      phenotypic features represents a basic procedure for a polyphasic approach on
      unambiguous bacterial isolate taxonomic classification.

PMID- 27882329
TI  - An Entropy-Based Position Projection Algorithm for Motif Discovery.
AB  - Motif discovery problem is crucial for understanding the structure and function
      of gene expression. Over the past decades, many attempts using consensus and
      probability training model for motif finding are successful. However, the most
      existing motif discovery algorithms are still time-consuming or easily trapped in
      a local optimum. To overcome these shortcomings, in this paper, we propose an
      entropy-based position projection algorithm, called EPP, which designs a
      projection process to divide the dataset and explores the best local optimal
      solution. The experimental results on real DNA sequences, Tompa data, and ChIP
      seq data show that EPP is advantageous in dealing with the motif discovery
      problem and outperforms current widely used algorithms.

PMID- 27882330
TI  - ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured
      Cardiomyocytes.
AB  - Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are
      present in various organs and involved in metabolizing aldehydes that are
      biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH
      isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced
      upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition
      of ALDH leads to the accumulation of unmetabolized 4HNE and consequently
      exacerbates injury in cells subjected to high glucose stress. H9C2 cardiomyocyte
      cell lines were pretreated with 10 MUM disulfiram (DSF), an inhibitor of ALDH2 or
      vehicle (DMSO) for 2 hours, and then subjected to high glucose stress {33 mM D
      glucose (HG) or 33 mM D-mannitol as an osmotic control (Ctrl)} for 24 hrs. The
      decrease in ALDH2 activity with DSF pretreatment was higher in HG group when
      compared to Ctrl group. Increased 4HNE adduct formation with DSF pretreatment was
      higher in HG group compared to Ctrl group. Pretreatment with DSF leads to
      potentiated HG-induced cell death in cultured H9C2 cardiomyocytes by lowering
      mitochondrial membrane potential. Our results indicate that ALDH2 activity is
      important in preventing high glucose induced cellular dysfunction.

PMID- 27882333
TI  - mHealth and eHealth for Obesity and Types 2 and 1 Diabetes.

PMID- 27882332
TI  - C-Peptide Levels Predict the Effectiveness of Dipeptidyl Peptidase-4 Inhibitor
      Therapy.
AB  - Background. Our aim was to define the conditions that affect therapeutic success
      when dipeptidyl peptidase-4 (DPP-4) inhibitor is added to metformin monotherapy.
      Materials and Methods. We reviewed the medical records of 56 patients who had
      received DPP-4 inhibitor as an add-on to metformin monotherapy and evaluated
      their response in the first year of therapy. Fasting blood glucose (FBG), HbA1c,
      C-peptide, and weight of the patients were recorded at 3-month intervals during
      the first year of treatment. Results. Patients who added DPP-4 inhibitor to
      metformin monotherapy had significant weight loss (P = 0.004) and FBG and HbA1c
      levels were significantly lowered during the first 6 months (both P < 0.001).
      Baseline levels of C-peptide were predictive for success of the treatment (P =
      0.02), even after correction for confounding factors, for example, age, gender,
      or BMI (P = 0.03). Duration of diabetes was not a predictor of response to
      treatment (P = 0.60). Conclusion. Our study demonstrates that in patients having
      inadequate glycemic control, the addition of a DPP-4 inhibitor as a second oral
      agent to metformin monotherapy provides better glycemic control, protects beta
      cell reserves, and does not cause weight gain. These effects depend on baseline C
      peptide levels.

PMID- 27882331
TI  - Ectopic Fat Deposition on Insulin Sensitivity: Correlation of Hepatocellular
      Lipid Content and M Value.
AB  - Purpose. This study aimed to explore the relationship among insulin sensitivity
      and ectopic fat depots in participants with different glucose status. Methods.
      Fifty-nine men and women were enrolled in this study: 29 with normal glucose
      tolerance (NGT), 17 with impaired glucose tolerance (IGT), and 13 with type 2
      diabetes mellitus (T2DM). All participants underwent a hyperinsulinemic
      euglycemic clamp to assess the insulin sensitivity index (M value) and magnetic
      resonance imaging to measure the hepatocellular lipid content (HCL), skeletal
      muscle fat content including intramyocellular lipid (IMCL) and extramyocellular
      lipid (EMCL) of tibialis anterior (ta), and soleus muscle (sol). Results. The M
      value of NGT group was higher than those of IGT and T2DM groups (P = 0.001).
      Participants with T2DM had the highest HCL and IMCL (ta) compared with those in
      NGT and IGT groups (P = 0.001). The M value had an inverse relationship with HCL
      (r = -0.789, P = 0.001), IMCL (sol) (r = -0.427, P = 0.002), and IMCL (ta) (r = 
      0.419, P = 0.002). Stepwise linear regression analysis showed that HCL
      (standardized beta = -0.416; P = 0.001) had an independent relationship with M
      value. Conclusions. Hepatocellular lipid content deposition happens earlier than
      skeletal muscle fat deposition. HCL is an independent risk factor for insulin
      resistance and may be used to evaluate the risk of developing T2DM as a
      noninvasive marker of insulin sensitivity index.

PMID- 27882336
TI  - Progressive insulin-derived amyloidosis in a patient with type 2 diabetes.
AB  - Here, we report a case of insulin-derived amyloidosis in the lower abdomen. The
      mass continued to develop even after the patient ceased injecting insulin into
      the mass. Histological examination led to a diagnosis of insulin-derived
      amyloidosis. Excision is preferable in cases of insulin-derived amyloidosis if
      patient's condition permits.

PMID- 27882335
TI  - ID(ealizing) control of adult subventricular zone neural stem/precursor cell
      differentiation for CNS regeneration.
AB  - The adult central nervous system (CNS) was considered a comparatively static
      tissue with little cell turnover. It is now well established that there is more
      plasticity than previously thought and that astrocytes act as neural
      stem/precursor cells (NSPCs) in the subventricular zone (SVZ). The discovery that
      these NSPCs can give rise to a limited number of new neurons, reactive astrocytes
      and oligodendrocytes contributing to brain repair in CNS disease, has raised
      hopes toward harnessing these cells for therapeutic interventions. Here, we will
      discuss the transcriptional control of adult NSPC differentiation into astrocytes
      in CNS disease focusing on the helix-loop-helix transcription factor protein
      family. In our recent study, we reported that elevated BMP-2 levels are
      translated into an increase in Id3 expression in adult NSPC subpopulations after
      cortical injury. Id3 then heterodimerizes with the basic helix-loop-helix
      transcription factor E47 and releases the E47-mediated repression of astrocyte
      specific gene expression. Consequently, adult NSPCs preferentially differentiate
      into astrocytes. We believe that understanding the in vivo differentiation
      potential and the molecular underpinnings of NSPCs in the adult mammalian brain
      will help us to evaluate their contributions to brain repair and may lead to new
      concepts in treating human CNS diseases.

PMID- 27882337
TI  - Dataset on species incidence, species richness and forest characteristics in a
      Danish protected area.
AB  - The data presented in this article are related to the research article entitled
      "Restoring hydrology and old-growth structures in a former production forest:
      Modelling the long-term effects on biodiversity" (A. Mazziotta, J. Heilmann
      Clausen, H. H.Bruun, O. Fritz, E. Aude, A.P. Tottrup) [1]. This article describes
      how the changes induced by restoration actions in forest hydrology and structure
      alter the biodiversity value of a Danish forest reserve. The field dataset is
      made publicly available to enable critical or extended analyses.

PMID- 27882334
TI  - Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor
      Microenvironment.
AB  - Our knowledge and understanding of the tumor microenvironment (TME) have been
      recently expanded with the recognition of the important role of innate lymphoid
      cells (ILC). Three different groups of ILC have been described based on their
      ability to produce cytokines that mediate the interactions between innate and
      adaptive immune cells in a variety of immune responses in infection, allergy, and
      autoimmunity. However, recent evidence from experimental models and clinical
      studies has demonstrated that ILC contribute to the mechanisms that generate
      suppressive or tolerant environments that allow tumor regression or progression.
      Defining the complex network of interactions and crosstalk of ILC with other
      immune cells and understanding the specific contributions of each type of ILC
      leading to tumor development will allow the manipulation of their function and
      will be important to develop new interventions and therapeutic strategies.

PMID- 27882338
TI  - Naturalistic rapid deceleration data: Drivers aged 75 years and older.
AB  - The data presented in this article are related to the research manuscript
      "Predictors of older drivers' involvement in rapid deceleration events", which
      investigates potential predictors of older drivers' involvement in rapid
      deceleration events including measures of vision, cognitive function and driving
      confidence (A. Chevalier et al., 2016) [1]. In naturalistic driving studies such
      as this, when sample size is not large enough to allow crashes to be used to
      investigate driver safety, rapid deceleration events may be used as a surrogate
      safety measure. Naturalistic driving data were collected for up to 52 weeks from
      182 volunteer drivers aged 75-94 years (median 80 years, 52% male) living in the
      suburban outskirts of Sydney. Driving data were collected using an in-vehicle
      monitoring device. Accelerometer data were recorded 32 times per second and
      Global Positioning System (GPS) data each second. To measure rapid deceleration
      behavior, rapid deceleration events (RDEs) were defined as having at least one
      data point at or above the deceleration threshold of 750 milli-g (7.35 m/s2). All
      events were constrained to a maximum 5 s duration. The dataset provided with this
      article contains 473 events, with a row per RDE. This article also contains
      information about data processing, treatment and quality control. The methods and
      data presented here may assist with planning and analysis of future studies into
      rapid deceleration behaviour using in-vehicle monitoring.

PMID- 27882339
TI  - Surface plasmon resonance biosensing of the monomer and the linked dimer of the
      variants of protein G under mass transport limitation.
AB  - This article presented the data related to the research article entitled
      "Calibration-free concentration analysis for an analyte prone to self
      association" (H. Imamura, S. Honda, 2017) [1]. The data included surface plasmon
      resonance (SPR) responses of the variants of protein G with different masses
      under mass transport limitation. The friction factors of the proteins analyzed by
      an ultracentrifugation were recorded. Calculation of the SPR response of the
      proteins was also described.

PMID- 27882340
TI  - Data on early postoperative changes in aqueous monocyte chemoattractant protein-1
      levels after phacoemulsification.
AB  - The data presented in this article are related to the research article entitled
      "Elevated levels of monocyte chemoattractant protein-1 in the aqueous humor after
      phacoemulsification" (M. Kawai, T. Inoue, M. Inatani, N. Tsuboi, K. Shobayashi,
      A. Matsukawa, A. Yoshida, H, 2012) [1]. The mean (+/-SE) aqueous MCP-1 levels
      (pg/ml) were 31.2+/-12.5, 1931.2+/-910.7, 2172.2+/-1015.7, 3315.4 +/-1535.8,
      3015.9 +/-914.4, 2709.0 +/-738.7, 72.8 +/-26.9, and 207.1+/-62.9 at 0, 3, 6, 12,
      24, 48, 168, and 720 h after phacoemulsification, respectively. The
      immunohistochemical analysis showed a number of MCP-1 positive inflammatory cells
      in the anterior chamber and conjunctiva. There were some MCP-1 positive cells in
      the corneal endothelium.

PMID- 27882341
TI  - Using MRI to predict future adverse cardiac remodelling in a male mouse model of
      myocardial infarction.
AB  - BACKGROUND: Mice are frequently used in research to examine outcomes of
      myocardial infarction (MI) and to investigate therapeutic interventions at an
      early pre-clinical stage. The MI model is generated by surgically occluding a
      major coronary artery, but natural variation in murine coronary anatomy can
      generate variable outcomes that will inevitably affect the accuracy of such
      investigations. The aim of this study was to use MRI to derive the most sensitive
      early variable that could be used to predict subsequent adverse cardiac
      remodelling in a male mouse model of MI. METHODS: Using a longitudinal study
      design, heart structure and function were evaluated using cardiac MRI at one week
      following surgical MI to generate the early measurements and again at four weeks,
      when the scar had matured. The primary variables measured at week one were left
      ventricular volumes at end systole (LV-ESV) and at end diastole (LV-EDV), infarct
      size, LV-cardiac mass, and ejection fraction (EF). RESULTS: Univariate and
      multiple regression analyses showed that LV-ESV at one week following MI could be
      used to accurately predict various parameters of adverse LV remodelling at four
      weeks post-MI. However, the highest correlation was between LV-ESV at one week
      following MI and LV-EDV at four weeks (r = 0.99; p < 0.0001), making LV-ESV at
      one week a valuable predictor variable of future adverse ventricular remodelling
      after MI. CONCLUSION: Using MRI to determine LV-ESV at an early stage following
      MI enables a more robust analysis of potential therapeutic interventions to
      ameliorate adverse cardiac remodelling.

PMID- 27882342
TI  - The Impact of Duodenal Diverticuli and the Execution of Endoscopic Retrograde
      Cholangiopancreaticography.
AB  - Introduction. Duodenal diverticuli alter the anatomy of the papillary region and
      can make an ERCP difficult. Aim. To study the outcome of ERCP in cases of
      duodenal diverticuli. Patients and Methods. Consecutive ERCPs in a period of 24
      years were included. Endoscopy reports were studied for presence of diverticuli.
      Success of the procedure and findings were noted. Clinical records were searched
      for clinical presentation of the patient. Patients without duodenal diverticuli
      were used as comparison. Results. 2795 procedures were done in 2092 patients. Of
      these, 211 (10%) had diverticuli. Diverticuli occurred significantly more often
      in women (p < 0.001). ERCP was significantly more often inconclusive in cases of
      a diverticulum, 12.8% versus 6.3%, p < 0.001. In cases of a successful ERCP,
      patients with diverticuli showed more often no abnormalities in the bile duct,
      26% versus 17%, p < 0.001. In 64% of cases, the reason for ERCP was cholestasis.
      There was no significant difference in presence of stones or cholangitis. Biliary
      pancreatitis was seen more often in patients without diverticuli, 4.4% versus
      1.4%, p = 0.04. This was also the case for malignancies, 18.5% versus 6.6%, p <
      0.001. Conclusion. It is concluded that duodenal diverticuli can be responsible
      for cholestasis. Presence of a diverticulum in the duodenum makes the ERCP
      procedure more complex.

PMID- 27882343
TI  - Proapoptotic protein Bim attenuates estrogen-enhanced survival in
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a progressive lung disease that primarily
      affects young women. Genetic evidence suggests that LAM cells bearing TSC2
      mutations migrate to the lungs, proliferate, and cause cystic remodeling. The
      female predominance indicates that estrogen plays a critical role in LAM
      pathogenesis, and we have proposed that estrogen promotes LAM cell metastasis by
      inhibition of anoikis. We report here that estrogen increased LAM patient-derived
      cells' resistance to anoikis in vitro, accompanied by decreased accumulation of
      the proapoptotic protein Bim, an activator of anoikis. The resistance to anoikis
      was reversed by the proteasome inhibitor, bortezomib. Treatment of LAM patient
      derived cells with estrogen plus bortezomib promoted anoikis compared with
      estrogen alone. Depletion of Bim by siRNA in TSC2-deficient cells resulted in
      anoikis resistance. Treatment of mice with bortezomib reduced estrogen-promoted
      lung colonization of TSC2-deficient cells. Importantly, molecular depletion of
      Bim by siRNA in Tsc2-deficient cells increased lung colonization in a mouse
      model. Collectively, these data indicate that Bim plays a key role in estrogen
      enhanced survival of LAM patient-derived cells under detached conditions that
      occur with dissemination. Thus, targeting Bim may be a plausible future treatment
      strategy in patients with LAM.

PMID- 27882344
TI  - SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and
      destabilizes kidney podocyte adhesion.
AB  - The repulsive guidance cue SLIT2 and its receptor ROBO2 are required for kidney
      development and podocyte foot process structure, but the SLIT2/ROBO2 signaling
      mechanism regulating podocyte function is not known. Here we report that a
      potentially novel signaling pathway consisting of SLIT/ROBO Rho GTPase activating
      protein 1 (SRGAP1) and nonmuscle myosin IIA (NMIIA) regulates podocyte adhesion
      downstream of ROBO2. We found that the myosin II regulatory light chain (MRLC), a
      subunit of NMIIA, interacts directly with SRGAP1 and forms a complex with
      ROBO2/SRGAP1/NMIIA in the presence of SLIT2. Immunostaining demonstrated that
      SRGAP1 is a podocyte protein and is colocalized with ROBO2 on the basal surface
      of podocytes. In addition, SLIT2 stimulation inhibits NMIIA activity, decreases
      focal adhesion formation, and reduces podocyte attachment to collagen. In vivo
      studies further showed that podocyte-specific knockout of Robo2 protects mice
      from hypertension-induced podocyte detachment and albuminuria and also partially
      rescues the podocyte-loss phenotype in Myh9 knockout mice. Thus, we have
      identified SLIT2/ROBO2/SRGAP1/NMIIA as a potentially novel signaling pathway in
      kidney podocytes, which may play a role in regulating podocyte adhesion and
      attachment. Our findings also suggest that SLIT2/ROBO2 signaling might be a
      therapeutic target for kidney diseases associated with podocyte detachment and
      loss.

PMID- 27882345
TI  - Institutional implementation of clinical tumor profiling on an unselected cancer
      population.
AB  - BACKGROUND. Comprehensive genomic profiling of a patient's cancer can be used to
      diagnose, monitor, and recommend treatment. Clinical implementation of tumor
      profiling in an enterprise-wide, unselected cancer patient population has yet to
      be reported. METHODS. We deployed a hybrid-capture and massively parallel
      sequencing assay (OncoPanel) for all adult and pediatric patients at our combined
      cancer centers. Results were categorized by pathologists based on actionability.
      We report the results for the first 3,727 patients tested. RESULTS. Our cohort
      consists of cancer patients unrestricted by disease site or stage. Across all
      consented patients, half had sufficient and available (>20% tumor) material for
      profiling; once specimens were received in the laboratory for pathology review,
      73% were scored as adequate for genomic testing. When sufficient DNA was
      obtained, OncoPanel yielded a result in 96% of cases. 73% of patients harbored an
      actionable or informative alteration; only 19% of these represented a current
      standard of care for therapeutic stratification. The findings recapitulate those
      of previous studies of common cancers but also identify alterations, including in
      AXL and EGFR, associated with response to targeted therapies. In rare cancers,
      potentially actionable alterations suggest the utility of a "cancer-agnostic"
      approach in genomic profiling. Retrospective analyses uncovered contextual
      genomic features that may inform therapeutic response and examples where
      diagnoses revised by genomic profiling markedly changed clinical management.
      CONCLUSIONS. Broad sequencing-based testing deployed across an unselected cancer
      cohort is feasible. Genomic results may alter management in diverse scenarios;
      however, additional barriers must be overcome to enable precision cancer medicine
      on a large scale. FUNDING. This work was supported by DFCI, BWH, and the National
      Cancer Institute (5R33CA155554 and 5K23CA157631).

PMID- 27882347
TI  - ML372 blocks SMN ubiquitination and improves spinal muscular atrophy pathology in
      mice.
AB  - Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease and
      one of the leading inherited causes of infant mortality. SMA results from
      insufficient levels of the survival motor neuron (SMN) protein, and studies in
      animal models of the disease have shown that increasing SMN protein levels
      ameliorates the disease phenotype. Our group previously identified and optimized
      a new series of small molecules, with good potency and toxicity profiles and
      reasonable pharmacokinetics, that were able to increase SMN protein levels in SMA
      patient-derived cells. We show here that ML372, a representative of this series,
      almost doubles the half-life of residual SMN protein expressed from the SMN2
      locus by blocking its ubiquitination and subsequent degradation by the
      proteasome. ML372 increased SMN protein levels in muscle, spinal cord, and brain
      tissue of SMA mice. Importantly, ML372 treatment improved the righting reflex and
      extended survival of a severe mouse model of SMA. These results demonstrate that
      slowing SMN degradation by selectively inhibiting its ubiquitination can improve
      the motor phenotype and lifespan of SMA model mice.

PMID- 27882346
TI  - Epigenetic regulation of macrophage polarization and inflammation by DNA
      methylation in obesity.
AB  - Obesity is associated with increased classically activated M1 adipose tissue
      macrophages (ATMs) and decreased alternatively activated M2 ATMs, both of which
      contribute to obesity-induced inflammation and insulin resistance. However, the
      underlying mechanism remains unclear. We find that inhibiting DNA methylation
      pharmacologically using 5-aza-2'-deoxycytidine or genetically by DNA
      methyltransferase 1 (DNMT1) deletion promotes alternative activation and
      suppresses inflammation in macrophages. Consistently, mice with myeloid DNMT1
      deficiency exhibit enhanced macrophage alternative activation, suppressed
      macrophage inflammation, and are protected from obesity-induced inflammation and
      insulin resistance. The promoter and 5'-untranslated region of peroxisome
      proliferator-activated receptor gamma1 (PPARgamma1) are enriched with CpGs and
      are epigenetically regulated. The saturated fatty acids stearate and palmitate
      and the inflammatory cytokine TNF-alpha significantly increase, whereas the TH2
      cytokine IL-4 significantly decreases PPARgamma1 promoter DNA methylation.
      Accordingly, inhibiting PPARgamma1 promoter DNA methylation pharmacologically
      using 5-aza-2'-deoxycytidine or genetically by DNMT1 deletion promotes macrophage
      alternative activation. Our data therefore establish DNA hypermethylation at the
      PPARgamma1 promoter induced by obesity-related factors as a critical determinant
      of ATM proinflammatory activation and inflammation, which contributes to insulin
      resistance in obesity.

PMID- 27882348
TI  - Humanized neuronal chimeric mouse brain generated by neonatally engrafted human
      iPSC-derived primitive neural progenitor cells.
AB  - The creation of a humanized chimeric mouse nervous system permits the study of
      human neural development and disease pathogenesis using human cells in vivo.
      Humanized glial chimeric mice with the brain and spinal cord being colonized by
      human glial cells have been successfully generated. However, generation of
      humanized chimeric mouse brains repopulated by human neurons to possess a high
      degree of chimerism have not been well studied. Here we created humanized
      neuronal chimeric mouse brains by neonatally engrafting the distinct and highly
      neurogenic human induced pluripotent stem cell (hiPSC)-derived rosette-type
      primitive neural progenitors. These neural progenitors predominantly
      differentiate to neurons, which disperse widely throughout the mouse brain with
      infiltration of the cerebral cortex and hippocampus at 6 and 13 months after
      transplantation. Building upon the hiPSC technology, we propose that this
      potentially unique humanized neuronal chimeric mouse model will provide profound
      opportunities to define the structure, function, and plasticity of neural
      networks containing human neurons derived from a broad variety of neurological
      disorders.

PMID- 27882349
TI  - The airway epithelium undergoes metabolic reprogramming in individuals at high
      risk for lung cancer.
AB  - The molecular determinants of lung cancer risk remain largely unknown. Airway
      epithelial cells are prone to assault by risk factors and are considered to be
      the primary cell type involved in the field of cancerization. To investigate risk
      associated changes in the bronchial epithelium proteome that may offer new
      insights into the molecular pathogenesis of lung cancer, proteins were identified
      in the airway epithelial cells of bronchial brushing specimens from risk
      stratified individuals by shotgun proteomics. Differential expression of selected
      proteins was validated by parallel reaction monitoring mass spectrometry in an
      independent set of individual bronchial brushings. We identified 2,869 proteins,
      of which 312 proteins demonstrated a trend in expression. Pathway analysis
      revealed enrichment of carbohydrate metabolic enzymes in high-risk individuals.
      Glucose consumption and lactate production were increased in human bronchial
      epithelial BEAS2B cells treated with cigarette smoke condensate for 7 months.
      Increased lipid biosynthetic capacity and net reductive carboxylation were
      revealed by metabolic flux analyses of [U-13C5] glutamine in this in vitro model,
      suggesting profound metabolic reprogramming in the airway epithelium of high-risk
      individuals. These results provide a rationale for the development of potentially
      new chemopreventive strategies and selection of patients for surveillance
      programs.

PMID- 27882351
TI  - Activity of NaV1.2 promotes neurodegeneration in an animal model of multiple
      sclerosis.
AB  - Counteracting the progressive neurological disability caused by neuronal and
      axonal loss is the major unmet clinical need in multiple sclerosis therapy.
      However, the mechanisms underlying irreversible neuroaxonal degeneration in
      multiple sclerosis and its animal model experimental autoimmune encephalomyelitis
      (EAE) are not well understood. A long-standing hypothesis holds that the
      distribution of voltage-gated sodium channels along demyelinated axons
      contributes to neurodegeneration by increasing neuroaxonal sodium influx and
      energy demand during CNS inflammation. Here, we tested this hypothesis in vivo by
      inserting a human gain-of-function mutation in the mouse NaV1.2-encoding gene
      Scn2a that is known to increase NaV1.2-mediated persistent sodium currents. In
      mutant mice, CNS inflammation during EAE leads to elevated neuroaxonal
      degeneration and increased disability and lethality compared with wild-type
      littermate controls. Importantly, immune cell infiltrates were not different
      between mutant EAE mice and wild-type EAE mice. Thus, this study shows that
      increased neuronal NaV1.2 activity exacerbates inflammation-induced
      neurodegeneration irrespective of immune cell alterations and identifies NaV1.2
      as a promising neuroprotective drug target in multiple sclerosis.

PMID- 27882352
TI  - Quantitative evaluation of the antiretroviral efficacy of dolutegravir.
AB  - The second-generation HIV-1 integrase strand transfer inhibitor (InSTI)
      dolutegravir (DTG) has had a major impact on the treatment of HIV-1 infection.
      Here we describe important but previously undetermined pharmacodynamic parameters
      for DTG. We show that the dose-response curve slope, which indicates
      cooperativity and is a major determinant of antiviral activity, is higher for DTG
      than for first-generation InSTIs. This steepness does not reflect inhibition of
      multiple steps in the HIV-1 life cycle, as is the case for allosteric integrase
      inhibitors and HIV-1 protease inhibitors. We also show that degree of
      independence, a metric of interaction favorability between antiretroviral drugs,
      is high for DTG and nucleoside reverse transcriptase inhibitors. Finally, we
      demonstrate poor selective advantage for HIV-1 bearing InSTI resistance
      mutations. Selective advantage, which incorporates both the magnitude of
      resistance conferred by a mutation and its fitness cost, explains the high
      genetic barrier to DTG resistance. Together, these parameters provide an
      explanation for the remarkable clinical success of DTG.

PMID- 27882350
TI  - Plasma vesicle miRNAs for therapy response monitoring in Hodgkin lymphoma
      patients.
AB  - BACKGROUND. Cell-free circulating nucleic acids, including 22-nt microRNAs
      (miRNAs), represent noninvasive biomarkers for treatment response monitoring of
      cancer patients. While the majority of plasma miRNA is bound to proteins, a
      smaller, less well-characterized pool is associated with extracellular vesicles
      (EVs). Here, we addressed whether EV-associated miRNAs reflect metabolic disease
      in classical Hodgkin lymphoma (cHL) patients. METHODS. With standardized size
      exclusion chromatography (SEC), we isolated EV-associated extracellular RNA
      (exRNA) fractions and protein-bound miRNA from plasma of cHL patients and healthy
      subjects. We performed a comprehensive small RNA sequencing analysis and
      validation by TaqMan qRT-PCR for candidate discovery. Fluorodeoxyglucose-PET (FDG
      PET) status before treatment, directly after treatment, and during long-term
      follow-up was compared directly with EV miRNA levels. RESULTS. The plasma EV
      miRNA repertoire was more extensive compared with protein-bound miRNA that was
      heavily dominated by a few abundant miRNA species and was less informative of
      disease status. Purified EV fractions of untreated cHL patients and tumor EVs had
      enriched levels of miR24-3p, miR127-3p, miR21-5p, miR155-5p, and let7a-5p
      compared with EV fractions from healthy subjects and disease controls. Serial
      monitoring of EV miRNA levels in patients before treatment, directly after
      treatment, and during long-term follow-up revealed robust, stable decreases in
      miRNA levels matching a complete metabolic response, as observed with FDG-PET.
      Importantly, EV miRNA levels rose again in relapse patients. CONCLUSION. We
      conclude that cHL-related miRNA levels in circulating EVs reflect the presence of
      vital tumor tissue and are suitable for therapy response and relapse monitoring
      in individual cHL patients. FUNDING. Cancer Center Amsterdam Foundation (CCA
      2013), Dutch Cancer Society (KWF-5510), Technology Foundation STW (STW
      Perspectief CANCER-ID).

PMID- 27882353
TI  - Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors.
AB  - Clinical monitoring of adoptive T cell transfer (ACT) utilizes serial blood
      analyses to discern T cell activity. While useful, these data are 1-dimensional
      and lack spatiotemporal information related to treatment efficacy or toxicity. We
      utilized a human genetic reporter, somatostatin receptor 2 (SSTR2), and PET, to
      quantitatively and longitudinally visualize whole-body T cell distribution and
      antitumor dynamics using a clinically approved radiotracer. Initial evaluations
      determined that SSTR2-expressing T cells were detectable at low densities with
      high sensitivity and specificity. SSTR2-based PET was applied to ACT of chimeric
      antigen receptor (CAR) T cells targeting intercellular adhesion molecule-1, which
      is overexpressed in anaplastic thyroid tumors. Timely CAR T cell infusions
      resulted in survival of tumor-bearing mice, while later infusions led to uniform
      death. Real-time PET imaging revealed biphasic T cell expansion and contraction
      at tumor sites among survivors, with peak tumor burden preceding peak T cell
      burden by several days. In contrast, nonsurvivors displayed unrelenting increases
      in tumor and T cell burden, indicating that tumor growth was outpacing T cell
      killing. Thus, longitudinal PET imaging of SSTR2-positive ACT dynamics enables
      prognostic, spatiotemporal monitoring with unprecedented clarity and detail to
      facilitate comprehensive therapy evaluation with potential for clinical
      translation.

PMID- 27882355
TI  - Cullin-3 mutation causes arterial stiffness and hypertension through a vascular
      smooth muscle mechanism.
AB  - Cullin-3 (CUL3) mutations (CUL3Delta9) were previously identified in hypertensive
      patients with pseudohypoaldosteronism type-II (PHAII), but the mechanism causing
      hypertension and whether this is driven by renal tubular or extratubular
      mechanisms remains unknown. We report that selective expression of CUL3Delta9 in
      smooth muscle acts by interfering with expression and function of endogenous
      CUL3, resulting in impaired turnover of the CUL3 substrate RhoA, increased RhoA
      activity, and augmented RhoA/Rho kinase signaling. This caused vascular
      dysfunction and increased arterial pressure under baseline conditions and a
      marked increase in arterial pressure, collagen deposition, and vascular stiffness
      in response to a subpressor dose of angiotensin II, which did not cause
      hypertension in control mice. Inhibition of total cullin activity increased the
      level of CUL3 substrates cyclin E and RhoA, and expression of CUL3Delta9
      decreased the level of the active form of endogenous CUL3 in human aortic smooth
      muscle cells. These data indicate that selective expression of the Cul3Delta9
      mutation in vascular smooth muscle phenocopies the hypertension observed in
      Cul3Delta9 human subjects and suggest that mutations in CUL3 cause human
      hypertension in part through a mechanism involving smooth muscle dysfunction
      initiated by a loss of CUL3-mediated degradation of RhoA.

PMID- 27882354
TI  - Bcl-2-associated athanogene 3 protects the heart from ischemia/reperfusion
      injury.
AB  - Bcl-2-associated athanogene 3 (BAG3) is an evolutionarily conserved protein
      expressed at high levels in the heart and the vasculature and in many cancers.
      While altered BAG3 expression has been associated with cardiac dysfunction, its
      role in ischemia/reperfusion (I/R) is unknown. To test the hypothesis that BAG3
      protects the heart from reperfusion injury, in vivo cardiac function was measured
      in hearts infected with either recombinant adeno-associated virus serotype 9
      expressing (rAAV9-expressing) BAG3 or GFP and subjected to I/R. To elucidate
      molecular mechanisms by which BAG3 protects against I/R injury, neonatal mouse
      ventricular cardiomyocytes (NMVCs) in which BAG3 levels were modified by
      adenovirus expressing (Ad-expressing) BAG3 or siBAG3 were exposed to
      hypoxia/reoxygenation (H/R). H/R significantly reduced NMVC BAG3 levels, which
      were associated with enhanced expression of apoptosis markers, decreased
      expression of autophagy markers, and reduced autophagy flux. The deleterious
      effects of H/R on apoptosis and autophagy were recapitulated by knockdown of BAG3
      with Ad-siBAG3 and were rescued by Ad-BAG3. In vivo, treatment of mice with rAAV9
      BAG3 prior to I/R significantly decreased infarct size and improved left
      ventricular function when compared with mice receiving rAAV9-GFP and improved
      markers of autophagy and apoptosis. These findings suggest that BAG3 may provide
      a therapeutic target in patients undergoing reperfusion after myocardial
      infarction.

PMID- 27882357
TI  - The influence of delta formation mechanism on geotechnical property sequence of
      the late Pleistocene-Holocene sediments in the Mekong River Delta.
AB  - The aim of the study was to characterize a variety of microstructure development
      levels and geotechnical property sequences of the late Pleistocene-Holocene
      deposits in the Mekong River delta (MRD), and the paper furthermore discusses the
      influences of delta formation mechanisms on them. The survey associated the
      geotechnical engineering and the sedimentary geology of the late Pleistocene
      Holocene deposits at five sites and also undifferentiated Pleistocene sediments.
      A cross-section which was rebuilt in the delta progradation-direction and between
      the Mekong and Bassac rivers represents the stratigraphy. Each sedimentary unit
      was formed under a different delta formation mechanism and revealed a typical
      geotechnical property sequence. The mechanical behaviors of the sediment
      succession in the tide-dominated delta with significant fluvial-activity and
      material source tend to be more cohesionless soils and strengths than those in
      the tide- and wave-dominated delta and even the coast. The particular tendency of
      the mechanical behavior of the deposit succession can be reasonably estimated
      from the delta formation mechanism. The characteristics of the clay minerals from
      the Mekong River produced the argillaceous soil which does not have extremely
      high plasticity. The microstructure development-levels are low to very high
      indicating how to choose hydraulic conductivity value, k, for estimating
      overconsolidation ratio, OCR, by the piezocone penetration tests (CPTU). The OCR
      of sediments in the delta types strangely change with depth but none less than 1.
      The post-depositional processes significantly influenced the microstructure
      development, particularly the dehydrating and oxidizing processes.

PMID- 27882356
TI  - Intra-osseous Co-transplantation of CD34-selected Umbilical Cord Blood and
      Mesenchymal Stromal Cells.
AB  - Human mesenchymal stromal cells (MSC) have been shown to support the growth and
      differentiation of hematopoietic stem cells (HSC). We hypothesized that intra
      osseous (IO) co-transplantation of MSC and umbilical cord blood (UCB) may be
      effective in improving early HSC engraftment, as IO transplantation has been
      demonstrated to enhance UCB engraftment in NOD SCID-gamma (NSG) mice. Following
      non-lethal irradiation (300rads), 6 groups of NSG mice were studied: 1)
      intravenous (IV) UCB CD34+ cells, 2) IV UCB CD34+ cells and MSC, 3) IO UCB CD34+
      cells, 4) IO UCB CD34+ cells and IO MSC, 5) IO UCB CD34+ cells and IV MSC, and 6)
      IV UCB CD34+ and IO MSC. Analysis of human-derived CD45+, CD3+, and CD19+ cells 6
      weeks following transplant revealed the highest level of engraftment in the IO
      UCB plus IO MSC cohort. Bone marrow analysis of human CD13 and CD14 markers
      revealed no significant difference between cohorts. We observed that IO MSC and
      UCB co-transplantation led to superior engraftment of CD45+, CD3+ and CD19+
      lineage cells in the bone marrow at 6 weeks as compared with the IV UCB cohort
      controls. Our data suggests that IO co-transplantation of MSC and UCB facilitates
      human HSC engraftment in NSG mice.

PMID- 27882358
TI  - Monofloral honeys by Sicilian black honeybee (Apis mellifera ssp. sicula) have
      high reducing power and antioxidant capacity.
AB  - Thirty samples from thirteen Sicilian monofloral honeys by the local black
      honeybee, and two honeydew honeys, were studied to assess phenol content,
      reducing power and antioxidant capacity as well as correlations among these
      parameters. Honeys from Apiaceae showed the highest phenol amount and capacity to
      reduce ferric ion and stable chemical radicals, whereas honeys from Leguminosae
      the lowest. All honeys were active against myoglobin-derived radicals usually
      formed in red meat after storage and/or heating and significant correlation (p =
      0.023) was found between flavonoid content and deactivation rate of this radical.
      Dill > almond > tangerine > thistle > sulla honeys inhibited formation of
      lipoperoxides in either iron/ascorbate or azoinitiator -induced membrane lipid
      oxidation, whereas eucalyptus honey was mostly effective in the metal-dependent
      model. Honeys by black honeybee possess remarkable reducing power and antioxidant
      potential against radicals of interest in dietary foodstuffs.

PMID- 27882359
TI  - Determination of the exchange constant of Tb0.3Dy0.7Fe2 by broadband
      ferromagnetic resonance spectroscopy.
AB  - We present measurements of the exchange stiffness D and the exchange constant A
      of a sputtered 80 nm Tb0.3Dy0.7Fe2 film. Using a broadband ferromagnetic
      resonance setup in a wide frequency range from 10 GHz to 50 GHz, multiple
      perpendicular standing spin-wave resonances were observed with the external
      static magnetic field applied in-plane. The field corresponding to the strongest
      resonance peak at each frequency is used to determine the effective
      magnetization, the g-factor and the Gilbert damping. Furthermore, the dependence
      of spin-wave mode on field-position is observed for several frequencies. The
      analysis of spin-wave resonance spectra at multiple frequencies allows precise
      determination of the exchange stiffness D = (2.79 +/- 0.02) * 10-17 T . m2 for an
      80 nm thick film. From this value, we calculated the exchange constant A = (9.1
      +/- 0.1) pJ . m-1.

PMID- 27882361
TI  - A versatile ferrocene-containing material as a p-type charge generation layer for
      high-performance full color tandem OLEDs.
AB  - A novel p-type charge generation material, DPAF, composed of a ferrocene core and
      a bis(biphenyl)amino group is designed and synthesized for application to tandem
      OLED devices. This molecular design not only enhances the thermal properties of
      ferrocene and the hole mobility, but also maintains its electrochemical
      stability. The red, green, and blue tandem OLEDs all give excellent device
      performance with low efficiency roll-off by using n-type C60 and p-type DPAFs as
      charge generation layers.

PMID- 27882360
TI  - Static and Dynamic Predictors of Foot Progression Angle in Individuals with and
      without Diabetes Mellitus and Peripheral Neuropathy.
AB  - INTRODUCTION: Foot progression angle (FPA) is a predictor of elevated regional
      plantar stresses and loads, which are indicators of dermal injury risk in
      individuals with diabetes mellitus and peripheral neuropathy (DMPN). FPA accounts
      for 15-45% of the variance in plantar stresses and loads in adults with DMPN.
      However, the biomechanical factors underlying an "out-toeing" gait pattern in
      this clinical population have not been examined. The primary purpose of this
      study was to identify static and dynamic predictors of foot progression angle
      magnitude in adults with and without DMPN. METHODS: Thirty-three adults with and
      12 adults without diabetes mellitus participated. Hip rotation, ankle
      dorsiflexion, and resting calcaneal stance position were measured using a
      standard goniometer. Kinematic and kinetic data were collected during walking.
      RESULTS AND DISCUSSION: Static predictor variables did not significantly predict
      foot progression angle magnitude using multiple regression analysis. Of the
      dynamic predictor variables, thigh and shank lateral rotation accounted for 37%
      of foot progression angle variance (p<.01). CONCLUSIONS: Our results show that
      dynamic measures of external rotation of proximal segments (thigh, shank) during
      gait are strong predictors of foot progression angle. Static measures of limited
      joint mobility and joint position do not predict foot progression angle. These
      findings suggest that targeting the thigh and shank rotation using verbal or
      tactile cueing may be a potential strategy when trying to alter walking movement
      patterns towards decreasing external (lateral) FPA to minimize risk of elevated
      regional plantar stresses in adults with DMPN at risk for ulceration.

PMID- 27882362
TI  - Tuning of chain chirality by interchain stacking forces and the structure
      property relationship in coordination systems constructed by meridional FeIII
      cyanide and MnIII Schiff bases.
AB  - We synthesized six Fe(iii)-Mn(iii) bimetallic compounds by self-assembling the
      newly developed mer-Fe cyanide PPh4[Fe(Clqpa)(CN)3].H2O (1) and
      PPh4[Fe(Brqpa)(CN)3].H2O (2) with Mn Schiff base Mn(5-Xsalen)+ cations. These
      compounds include [Fe(Xqpa)(CN)3][Mn(5-Ysalen)].pMeOH.qH2O [qpaH2 = N-(quinolin-8
      yl)picolinamide; salen = N,N'-ethylenebis(salicylideneiminato) dianion; X = Cl, Y
      = H (3); X = Cl, Y = Br (4); X = Br, Y = H (5); X = Br, Y = F (6); X = Br, Y = Cl
      (7); X = Br, Y = Br (8)]. When precursor 1 was used, compounds 3 and 4 were
      isolated to give a dinuclear entity and a linear chain structure, respectively.
      The reaction of precursor 2 with the Schiff bases afforded four linear Fe(iii)
      Mn(iii) chain complexes. Chain chirality with P- and M-helicity emerges in 4, 7,
      and 8, while 5 exhibits chain helicity opposite to the previous chain complexes
      and 6 presents no chain helicity. Such a structural feature is heavily dependent
      on the interchain pi-pi contacts and the Fe precursor bridging unit. Chiral
      induction from a local ethylenediamine link of Y-salen is propagated over the
      chain via noncovalent pi-pi interactions. All the bimetallic compounds show
      antiferromagnetic interactions transmitted by the cyanide linkage. A field
      induced metamagnetic transition is involved in 4, 7, and 8, while a field-induced
      two-step transition is evident in 6. From a magnetostructural viewpoint, the
      coupling constant is primarily governed by the Mn-Nax-Cax angle (ax = axial) in
      the bimetallic chain complexes composed of mer-Fe(iii) tricyanides, although the
      torsion angle plays a role.

PMID- 27882363
TI  - Transition metal complex directed lead bromides with tunable structures and
      visible light driven photocatalytic properties.
AB  - With similar transition metal (TM) complex cations as structural directing agents
      (SDAs), six new hybrid lead bromides were synthesized and structurally
      characterized as [Co(2,2-bipy)3]2{[Co(2,2-bipy)]3Pb7Br24} (1), [Co(2,2
      bipy)2Br]PbBr3 (2), [TM(phen)3]Pb2Br6 (TM = Co (3) and Ni (4)), [Co(2,2
      bipy)3]Pb3Br9 (5) and [Co(2,2-bipy)3]Pb5Br13.CH3CN (6) with distinct structural
      types from zero-dimensional (0D) unit, one-dimensional (1D) chain to two
      dimensional (2D) layer. Compound 1 contains the 0D {[Co(bipy)]3Pb7Br24}4- units
      built from the [Pb7Br24] ring attached by three unsaturated [Co(2,2-bipy)]2+
      complexes via Co-Br bonds. Under the direction actions of different SDAs,
      compounds 2 and 3-4 contain two different types of [Pb2Br6]4- chains based on the
      same octahedral [PbBr6] units but with distinct connecting manners, respectively.
      Using the same [Co(2,2-bipy)3]3+ as SDA, compound 5 reveals a 1D [Pb3Br9]3-
      double chain, whereas compound 6 features a 2D complex [Pb5Br13]3- layer. The
      UV/vis diffuse-reflectance measurements reveal that the title compounds feature
      tunable band gaps of 1.70-2.29 eV. Under the visible light irradiation, sample 6
      exhibits efficient and stable photocatalytic degradation activities over organic
      pollutants, which mainly originates from the multi-electronic effects of the TM
      complex cations. A possible photocatalytic mechanism is also proposed based on
      the radical trapping experiments and electronic band structural calculations.

PMID- 27882364
TI  - Regioselective, cascade [3+2] annulation of beta-naphthols (resorcinols) with Z
      enoate propargylic alcohols: a novel entry for the synthesis of complex
      naphtho(benzo)furans.
AB  - An acid promoted, unprecedented cascade [3+2] annulation strategy for the
      synthesis of complex naphtho- and benzofurans is reported. An alkoxyfuranylallene
      intermediate (generated from Z-enoate propargylic alcohols via a Meyer-Schuster
      rearrangement) was employed as the 1,2-bis-electrophile and beta-naphthols
      (phenols) as 1,3-bisnucleophiles. This strategy represents the first cascade and
      metal free process for the synthesis of naphthofurans and benzofurans from
      propargylic alcohols. A very broad substrate scope was observed. The synthesized
      naphtho- and benzofurans were efficiently transformed into the frameworks of the
      bioactive natural products amycofuran and frondosin B.

PMID- 27882366
TI  - A highly active and stable palladium catalyst on a g-C3N4 support for direct
      formic acid synthesis under neutral conditions.
AB  - Graphitic carbon nitride (g-C3N4) is applied as a support of the Pd catalyst for
      direct HCOOH synthesis by CO2 hydrogenation under neutral conditions. The high
      CO2 affinity of g-C3N4 is responsible for the enhanced catalytic activity and
      stability relative to the inert support such as a carbon nanotube.

PMID- 27882365
TI  - Highly efficient three-component coupling reaction catalysed by atomically
      precise ligand-protected Au38(SC2H4Ph)24 nanoclusters.
AB  - The catalytic potential of atomically precise quantum-sized gold nanoclusters
      (Au38(SC2H4Ph)24) is explored for the three-component coupling of an aldehyde, an
      alkyne and an amine to synthesize propargylamines. A high catalytic efficiency
      with a very low loading (0.01 mol%) is achieved. Furthermore, the synergistic
      effect of the electron-deficient surface (i.e. Audelta+, 0 < delta+ < 1) and the
      electron-rich Au23 core of the ligand-protected nanoclusters is critical for this
      catalytic reaction.

PMID- 27882367
TI  - Copper(i)-NHC complexes as NHC transfer agents.
AB  - This report presents the recent advances in the use of copper(i)-NHC (NHC = N
      heterocyclic carbene) complexes as transmetallating agents enabling the transfer
      of NHCs to a wide range of transition metals. The synthesis of these carbene
      transfer reagents is also discussed.

PMID- 27882369
TI  - Regio- and stereo-selective polymerization of 1,3-butadiene catalyzed by
      phosphorus-nitrogen PN3-pincer cobalt(ii) complexes.
AB  - A new family of cobalt complexes (CoCl2-H, CoCl2-Me, CoCl2-iPr, CoBr2-H, CoBr2
      Me, CoBr2-iPr, CoI2-H, CoI2-Me, and CoI2-iPr) supported by a PN3 ligand (6-(N,N'
      di-t-butylphosphino)-2-pyrazol-yl-aminopyridine) have been prepared and fully
      characterized by FT-IR, elemental analysis, and X-ray analysis. The X-ray
      analysis reveals a trigonal bipyramidal conformation in the solid state for all
      representative complexes, CoCl2-H, CoBr2-H, CoBr2-iPr and CoI2-Me. The cobalt
      center is chelated by the PN3 ligand through the pyridinyl nitrogen, the pyrazol
      nitrogen and the phosphorus donor, with a long Co-P bond distance indicating a
      labile character. On activation with AlEt2Cl, Al2Et3Cl3, MAO, [Ph3C]+[B(C6F5)4]
      /AliBu3 or AliBu3, cis-1,4 selective butadiene polymerization was achieved with
      up to 98.6% selectivity. The polymerization results show that the cis-1,4
      selectivity is influenced by the steric hindrance, increasing with the bulkiness
      of the substituent groups (CoX2-iPr > CoX2-Me > CoX2-H) at the 3,5-positions of
      the pyrazole moiety, together with a slight decrease in activity. The activity
      changes in the order CoCl2L ~ CoBr2L > CoI2L (for the same ligand L) when MAO is
      used as the activator, while the high level of cis-1,4 selectivity is maintained.
      It is possible to switch the selectivity from cis-1,4 to syndiotactic-1,2 by
      adding PPh3.

PMID- 27882368
TI  - An unusual co-crystal [(MU2-dcpm)Ag2(MU2-O2CH)(eta2-NO3)]2.[(MU2-dcpm)2Ag4(MU2
      NO3)4] and its connection to the selective decarboxylation of formic acid in the
      gas phase.
AB  - ESI/MS of an acetonitrile solution containing a mixture of AgNO3 : 
      bis(dicyclohexylphosphino)methane (dcpm, L) : NaO2CH in a molar ratio of 2 : 1 :
      1 gave an abundant peak due to [LAg2(O2CH)]+ and a minor peak assigned as
      [L2Ag4(O2CH)3]+. When this acetonitrile solution was frozen and layered with
      diethyl ether and left undisturbed for six days, crystalline material suitable
      for X-ray crystallography was identified and separated from amorphous solids.
      Single crystal X-ray diffraction revealed an unusual co-crystal consisting of two
      discrete tetranuclear silver clusters [(MU2-dcpm)Ag2(MU2-O2CH)(eta2-NO3)]2.[(MU2
      dcpm)2Ag4(MU2-NO3)4]. While all of the coordinated formates in [LAg2(O2CH)]+ and
      [L2Ag4(O2CH)3]+ can be decarboxylated in the gas-phase under conditions of
      collision induced dissociation, only the hydride [LAg2(H)]+ thus formed reacts
      with formic acid via protonation and liberation of H2 to regenerate to formate,
      thereby closing a catalytic cycle for the selective decomposition of formic acid.

PMID- 27882370
TI  - Anti-obesity effects of Arctii Fructus (Arctium lappa) in white/brown adipocytes
      and high-fat diet-induced obese mice.
AB  - Arctii Fructus is traditionally used in oriental pharmacies as an anti
      inflammatory medicine. Although several studies have shown its anti-inflammatory
      effects, there have been no reports on its use in obesity related studies. In
      this study, the anti-obesity effect of Arctii Fructus was investigated in high
      fat diet (HFD)-induced obese mice, and the effect was confirmed in white and
      primary cultured brown adipocytes. Arctii Fructus inhibited weight gain and
      reduced the mass of white adipose tissue in HFD-induced obese mice. Serum levels
      of triglyceride and LDL-cholesterol were reduced, and HDL-cholesterol was
      increased in the Arctii Fructus treated group. In 3T3-L1 cells, a water extract
      (WAF) and 70% EtOH extract (EtAF) of Arctii Fructus significantly inhibited
      adipogenesis and suppressed the expression of proliferator-activated receptor
      gamma and CCAAT/enhancer-binding protein alpha. In particular, EtAF activated the
      phosphorylation of AMP-activated protein kinase. On the other hand, uncoupling
      protein 1 and peroxisome proliferator-activated receptor gamma coactivator 1
      alpha, known as brown adipocytes specific genes, were increased in primary
      cultured brown adipocytes by WAF and EtAF. This study shows that Arctii Fructus
      prevents the development of obesity through the inhibition of white adipocyte
      differentiation and activation of brown adipocyte differentiation which suggests
      that Arctii Fructus could be an effective therapeutic for treating or preventing
      obesity.

PMID- 27882371
TI  - Anti-hyperlipidemia and antioxidant activities of Amygdalus pedunculata seed oil.
AB  - This study attempts to evaluate the beneficial effects of Amygdalus pedunculata
      seed oil (AO) on the lipid profile and antioxidant status of high-fat fed rats
      and d-galactose (d-gal)-induced oxidative mice. The anti-hyperlipidemia effects
      of AO were evaluated. AO supplementation (2%, 4%, and 8%) for three weeks
      significantly decreased the total cholesterol (TC), triglyceride (TG), and low
      density lipoprotein (LDL) levels and increased the high-density lipoprotein (HDL)
      levels in the high fat diet rats unlike in the model group. The antioxidant
      activities of AO were determined in the d-gal-injected mice. Results showed that
      AO (2%, 4%, and 8%) enhanced the activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-Px), as well as lowered the levels of alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde
      (MAD) in the liver of d-gal-injected mice. Compared with olive oil (OO) and
      rapeseed oil (RSO), the results of tests indicated that AO lowered the
      hyperlipidemia risk factors by improving plasma antioxidant defenses and lipid
      profiles.

PMID- 27882372
TI  - Highly efficient nitrogen chelated ruthenium carbene metathesis catalysts.
AB  - A series of nitrogen chelated ruthenium carbene metathesis catalysts containing
      an N-heterocyclic carbene (NHC) and a carbonyl group have been developed and
      their catalytic activities for olefin metathesis reactions were investigated. The
      X-ray structure of the [(H2IMes)(Cl)2Ru]C(H)CH2[p-F(C6H3)NC(CF3)(C(O)OCH2CH3)]
      complex shows that the carbonyl oxygen of the ester and the imine nitrogen are
      both coordinated to the Ru metal to give an octahedral structure. The catalytic
      activity of these ruthenium carbene complexes for olefin metathesis reactions was
      tested. Some of the complexes bearing electron withdrawing groups had high
      initiation rates. These complexes exhibited excellent performance for both ring
      closing metathesis and cross metathesis.

PMID- 27882373
TI  - Arylamino radical complexes of ruthenium and osmium: dual radical counter in a
      molecule.
AB  - Radical and non-radical ruthenium and osmium complexes of 1-amino-9,10
      anthraquinone (AqNH2), which is defined as a molecule of dual radical counter,
      are disclosed. 1-Amido-9,10-anthraquinone (AqNH-) complexes of the types trans
      [RuII(AqNH-)(PPh3)2(CO)Cl] (1), trans-[OsII(AqNH-)(PPh3)2(CO)Br] (2) and trans
      [RuIII(AqNH-)(PPh3)2Cl2] (3) were isolated. AqNH- of 1-3 is redox active and
      undergoes oxidation reversibly at +(0.05-0.35) V to the 1-amino-9,10
      anthraquinone radical (AqNH) and reduction at -(0.86-1.60) V to the 1-amido-9,10
      anthrasemiquinonate anion radical (AqNHSQ2-). The reaction of 2 with I2 in CH2Cl2
      afforded a crystalline AqNH complex of the type trans
      [OsII(AqNH)(PPh3)2(CO)Br]+I5-.1/2I2 (2+I5-.1/2I2). AqNH and AqNHSQ2- complexes of
      the types trans-[RuII(AqNH)(PPh3)2(CO)Cl]+ (1+), trans-[RuIII(AqNH)(PPh3)2Cl2]+
      (3+), trans-[RuII(AqNHSQ2-)(PPh3)2(CO)Cl]- (1-) and trans-[OsII(AqNHSQ2
      )(PPh3)2(CO)Br]- (2-) were generated chemically/electrochemically in solution.
      The electronic states of the complexes were authenticated by single crystal X-ray
      structure determinations of 1, 2.5/4 toluene, 3 and 2+I5-.1/2I2, EPR spectroscopy
      and density functional theory (DFT) calculations. AqNH instigates a 2c-3e ppi-dpi
      interaction and the length in 2+I5-.1/2I2, 1.978(5) A, is relatively shorter than
      the OsII-NHAq- length, 2.037(2) A, while the Aq-NH bond, 1.365(8) A, is longer
      than the Aq-NH- bond, 1.328(3) A. DFT calculations predicted that the atomic spin
      is delocalized over the ligand backbone (1+, 56%) particularly in one of the p
      orbitals of the nitrogen and the metal atoms of the 1+ and 2+ ions, while the
      spin is dominantly localized on the anthraquinone fragment of the 1- and 2- ions.
      TD DFT calculations were employed to elucidate the origins of the lower energy
      absorption bands of the neutral complexes. Hypsochromic shifts of the UV-vis-NIR
      absorption maximum during 1->1+, 2->2+ and 3->3+ conversions were recorded by
      spectroelectrochemical measurements.

PMID- 27882374
TI  - Cancer-associated venous thromboembolism: Burden, mechanisms, and management.
AB  - Venous thromboembolism (VTE) is a significant health problem in the general
      population but especially in cancer patients. In this review, we discuss the
      epidemiology and burden of the disease, the pathophysiology of cancer-associated
      VTE, and the clinical treatment options for both primary prevention and acute
      treatment. Overall, the development of VTE in cancer patients is related to
      increases in morbidity, mortality, and medical costs. However, the incidence of
      cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia,
      comorbidities, performance status, history of venous diseases), tumour-related
      factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g.
      surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive
      treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes)
      and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for
      the risk of VTE in cancer patients and have been used to enhance risk
      stratification. Evidence suggests that cancer itself is associated with a state
      of hypercoagulability, driven in part by the release of procoagulant factors,
      such as tissue factor, from malignant tissue as well as by inflammation-driven
      activation of endothelial cells, platelets, and leukocytes. In general, low
      molecular-weight heparin (LWMH) monotherapy is the standard of care for the
      management of cancer-associated VTE, as vitamin K antagonists are less effective
      in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially
      promising treatment option for cancer patients with VTE, but recommendations
      concerning the routine use of DOACs should await head-to-head studies with LMWH.

PMID- 27882375
TI  - Risk factors for intracranial haemorrhage in patients with pulmonary embolism
      treated with thrombolytic therapy Development of the PE-CH Score.
AB  - Pulmonary embolism (PE) is a major cause of morbidity and mortality world-wide,
      and the use of thrombolytic therapy has been associated with favourable clinical
      outcomes in certain patient subsets. These potential benefits are counterbalanced
      by the risk of bleeding complications, the most devastating of which is
      intracranial haemorrhage (ICH). We retrospectively evaluated 9703 patients from
      the 2003-2012 nationwide in-patient sample database (NIS) who received
      thrombolytics for PE. All patients with ICH during the PE hospitalisation were
      identified and a clinical risk score model was developed utilizing demographics
      and comorbidities. The dataset was divided 1:1 into derivation and validation
      cohorts. During 2003-2012, 176/9705 (1.8 %) patients with PE experienced ICH
      after thrombolytic use. Four independent prognostic factors were identified in a
      backward logistic regression model, and each was assigned a number of points
      proportional to its regression coefficient: pre-existing Peripheral vascular
      disease (1 point), age greater than 65 years (Elderly) (1 point), prior
      Cerebrovascular accident with residual deficit (5 points), and prior myocardial
      infarction (Heart attack) (1 point). In the derivation cohort, scores of 0, 1, 2
      and >= 5 points were associated with ICH risks of 1.2 %, 1.9 %, 2.4 % and 17.8 %,
      respectively. Rates of ICH were similar in the validation cohort. The C-statistic
      for the risk score was 0.65 (0.61-0.70) in the derivation cohort and 0.66 (0.60
      0.72) in the validation cohort. A novel risk score, derived from simple clinical
      historical elements was developed to predict ICH in PE patients treated with
      thrombolytics.

PMID- 27882376
TI  - Plasma levels of the anti-coagulation protein C and the risk of ischaemic heart
      disease. A Mendelian randomisation study.
AB  - Protein C is an environmentally modifiable anticoagulant, which protects against
      venous thrombosis, whether it also protects against ischaemic heart disease is
      unclear, based on observational studies and relatively small genetic studies. It
      was our study aim to clarify the role of protein C in ischaemic heart disease.
      The risk of coronary artery disease/myocardial infarction (CAD/MI) was assessed
      according to genetically predicted protein C in very large studies. Associations
      with lipids and diabetes were similarly assessed to rule out effects via
      traditional cardiovascular disease risk factors. Separate sample instrumental
      variable analysis with genetic instruments (Mendelian randomisation) was used to
      obtain an unconfounded estimate of the association of protein C (based on
      (rs867186 (PROCR), rs3746429 (EDEM2), rs7580658 (inter/PROC)) with CAD/MI in an
      extensively genotyped case (n=64374)-control (n=130681) study, CARDIoGRAMplusC4D.
      Associations with lipids and diabetes were similarly assessed using the Global
      Lipids Genetics Consortium Results (n=196,475) and the DIAbetes Genetics
      Replication And Meta-analysis case (n=34,380)-control (n=114,981) study.
      Genetically predicted protein C was negatively associated with CAD/MI, odds ratio
      (OR) 0.85 ug/ml, 95 % confidence interval 0.80 to 0.90, but had no such negative
      association with lipids or diabetes. Results were similar for the SNP rs867186
      functionally relevant to protein C, and including additional potentially
      pleiotropic SNPs (rs1260326 (GCKR), rs17145713 (BAZ1B) and rs4321325 (CYP27C1)).
      In conclusion, protein C may protect against CAD/MI. Whether environmental or
      dietary items that raise protein C protect against ischaemic cardiovascular
      disease by that mechanism should be investigated.

PMID- 27882378
TI  - Eastern Health Alliance Scientific Meeting 2016. Transitions of Care. Singapore,
      10-12 November 2016. Proceedings and abstracts.

PMID- 27882379
TI  - Alexandra Health Forum in conjunction with AH Nursing Fest 2014. Healthcare
      Beyond Limits: Transcending People, Place and Time. Singapore, 6-8 November 2014.
      Proceedings and abstracts.

PMID- 27882377
TI  - Alexandra Health Forum in conjunction with AH Nursing Fest. Healthcare for the
      Future: Shifting Paradigms for Population, Patients and Professionals. Singapore,
      25-27 August 2016. Proceedings and abstracts.

PMID- 27882380
TI  - Alexandra Health Forum in conjunction with AH Nursing Fest 2012. Integrative Care
      towards Better Patient Outcome. Singapore, 30 August-1 September 2012.
      Proceedings and abstracts.

PMID- 27882381
TI  - Alexandra Health Research Forum 2011. New Frontiers: Translating research into
      clinical practice. Singapore, 18-19 February 2011. Proceedings and abstracts.

PMID- 27882382
TI  - 6th KKH Annual Scientific Meeting 2011. Academic Excellence Towards Better
      Healthcare for Women and Children. Singapore, 15-16 July 2011. Proceedings and
      abstracts.

PMID- 27882383
TI  - Becker Naevus Syndrome of the Lower Body: One Case and Review of the Literature.
AB  - Becker naevus syndrome is a rare epidermal naevus syndrome defined by the co
      occurrence of a Becker naevus with various cutaneous, muscular and skeletal
      anomalies. In the majority of cases, abnormalities exclusively consist of
      ipsilateral hypoplasia of the breast, areola and/or nipple in addition to the
      naevus. Here, we report on a 42-year-old woman with an extensive Becker naevus
      reaching from the left buttock to the left calf verified on histological
      examination. In addition, there was marked hypoplasia of the fatty tissue of the
      left thigh confirmed by magnetic resonance imaging in contrast to hyperplasia of
      the fatty tissue of the left gluteal area. Underlying muscles and bones were not
      affected. There was no difference in leg lengths. In addition, we review and
      discuss the features of Becker naevus syndrome with emphasis on 10 reported cases
      with involvement of the lower body.

PMID- 27882384
TI  - Prevalence of Mycoplasma genitalium Infection and Relationship with Symptoms
      Among Adults Attending a Sexual Health Centre.

PMID- 27882385
TI  - A Role for Neuregulin-1 in Promoting Keloid Fibroblast Migration via ErbB2
      mediated Signaling.
AB  - Keloid disease is a fibroproliferative tumour characterised by aggressive local
      invasion, evident from a clinically and histologically active migrating margin.
      During combined laser capture microdissection and microarray analysis-based in
      situ gene expression profiling, we identified upregulation of the polypeptide
      growth factor neuregulin-1 (NRG1) and ErbB2 oncogene in keloid margin dermis,
      leading to the hypothesis that NRG1 contributed to keloid margin migration
      through ErbB2-mediated signalling. The aim of this study was to probe this
      hypothesis through functional in vitro studies. Exogenous NRG1 addition to keloid
      and normal skin fibroblasts altered cytokine expression profiles, significantly
      increased in vitro migration and keloid fibroblast Src and protein tyrosine
      kinase 2 (PTK2/FAK) gene expression. ErbB2 siRNA knockdown attenuated both keloid
      fibroblast migration and Src/PTK2 expression, which were not recovered following
      NRG1 administration, suggesting the NRG1/ErbB2/Src/PTK2 signaling pathway may be
      a novel regulator of keloid fibroblast migration, and representing a potential
      new therapeutic target.

PMID- 27882386
TI  - Factors Associated with Receiving Biologics or Classic Systemic Therapy for
      Moderate-to-Severe Psoriasis: Evidence from the PSONET Registries.

PMID- 27882387
TI  - Bacterial Colonization in Hidradenitis Suppurativa/Acne Inversa: A Cross
      sectional Study of 50 Patients and Review of the Literature.
AB  - It is unclear whether bacterial colonization in hidradenitis suppurativa/acne
      inversa (HS) comprises a primary cause, triggering factor or secondary phenomenon
      of the disease pathogenesis. Furthermore, the connection between certain
      bacterial species, the disease severity and its localization is unknown.
      Bacterial species were isolated from HS lesions to reveal a potential correlation
      with localization and disease severity. Ninety swab tests were prospectively
      obtained from 90 HS lesions of 50 consecutive patients. The material was cultured
      under aerobic and anaerobic conditions. The identified species were statistically
      correlated with Hurley stage and localization of the lesions. The most prevalent
      isolates were reported. Hurley stage significantly correlated with disease
      localization. Particular bacterial species were associated with "extended"
      disease and Hurley III stage with the detection of both aerobic and anaerobic
      bacteria and with a higher number of species. The presence of bacterial species
      is dependent on the local milieu, which correlates with the localization of the
      disease, its clinical manifestations and its extension.

PMID- 27882388
TI  - Sudden Onset of an Itchy Papular Eruption: A Quiz.

PMID- 27882389
TI  - Linear IgA Bullous Dermatosis Associated with Immunoglobulin Light-chain
      Amyloidosis.

PMID- 27882390
TI  - [Highest level of clinical competence for endovascular interventions].

PMID- 27882391
TI  - [Palliative care for patients with Turkish or Arabic migration background in
      Lower Saxony : A survey from palliative care professionals' perspective].
AB  - BACKGROUND AND OBJECTIVES: People with a migration background (MB) are an
      important part of German society. If and how they use specialised palliative care
      (SPC) has not been studied. We aimed to assess the current SPC for patients with
      Turkish or Arabic MB (the largest group of immigrants in Germany with a shared
      ascribed culture) from the point of view of healthcare professionals (HCP) in
      Lower Saxony. METHOD: All HCPs in institutions providing SPC (n = 90) were
      invited to participate in an anonymous online survey which contained closed and
      open questions about care for this patient group, characteristics of the last
      patient with Turkish or Arabic MB they cared for, and resources and strategies to
      care for these patients. The survey was analysed using descriptive statistics and
      qualitative content analysis. RESULTS: Fifty-five HCPs in SPC participated,
      mostly nurses aged between 40 and 60 years. One fifth had not cared for a patient
      with Turkish or Arabic MB during the last 12 months. Given their local
      population, 84.6% estimated that they cared for a lower number of patients than
      would be representative. In care, problems with communication as well as
      difficulties to interact with and manage families, and in organising and planning
      care were most prevalent. Only 21% of participants had access to interpreters.
      DISCUSSION: Patients with Turkish or Arabic MB seem to be underrepresented in
      SPC. The high rate of communication problems highlights the necessity of reliable
      and accessible interpreter services. Most difficulties were of psychosocial
      nature, showing how important the holistic approach of SPC is in caring for
      terminally ill patients with Turkish or Arabic MB.

PMID- 27882392
TI  - [The special requirements of old age in terms of dying].
AB  - It is expected that the rising average life expectancy will leave ever more
      people with chronic progressive diseases of the body and brain. This then means
      not only having to deal with increasingly longer periods of care, but also
      possibly distinct neurocognitive disorders in the years prior to death and dying.
      The aim of this study is to report epidemiological data on the causes of death,
      as well as on the places of death. In addition, the attitudes and behaviour
      towards death and dying, as well as the different places of death will be
      discussed. Expecting support in the process of dying, as well as factors that
      have a more conducive effect on the internal processing of dying, are mentioned.
      At the same time, the attitudes and behaviours in respect of the accompaniment of
      dying people, which can be seen in the staff in clinical inpatient facilities,
      are addressed. Personal intense grappling with dying and death actually has a
      positive effect on these behaviours and attitudes. Finally, the contribution
      turns to the question of to what extent the theory of compression of morbidity
      may be perceived as valid, especially in view of the rising average life
      expectancy. It is emphasised that chronic diseases, even when no functional loss
      is present, place not only great demands on the patient, but also on the care
      system and financial resources. Furthermore, it is demonstrated that frailty can
      often cause mental disorders. Specific requirements with a view to the care of
      people with dementia are given.

PMID- 27882395
TI  - ?

PMID- 27882394
TI  - [Economic aspects of oncological esophageal surgery : Centralization is
      essential].
AB  - The incidence of esophageal carcinoma has increased in recent years in Germany.
      The aim of this article is a discussion of the economic aspects of oncological
      esophageal surgery within the German diagnosis-related groups (DRG) system
      focusing on the association between minimum caseload requirements and outcome
      quality as well as costs. The margins for the DRG classification G03A are low and
      quickly exhausted if complications determine the postoperative course. A current
      study using nationwide German hospital discharge data proved a significant
      difference in hospital mortality between clinics with and without achieving the
      minimum caseload requirements for esophagectomy. Data from the USA clearly showed
      that besides patient-relevant parameters, the caseload of a surgeon is relevant
      for the cost of treatment. Such cost-related analyses do not exist in Germany at
      present. Scientific validation of reliable minimum caseload numbers for
      oncological esophagectomy is desirable in the future.

PMID- 27882393
TI  - [Medical activities by nonmedical personnel : The way to the madhouse or a
      calculated risk?]

PMID- 27882396
TI  - Athina Markou's contributions to treatment development for mental illnesses: a
      perspective.

PMID- 27882397
TI  - Reply by L. Maffioli.

PMID- 27882400
TI  - [Questionnaire study for patients with low-risk prostate cancer : Therapy
      decision and coping strategies after a diagnosis of low-risk prostate cancer
      (COPCa) - study AP 91/15 from the AUO].

PMID- 27882398
TI  - Supine position and REM dependence in obstructive sleep apnea : Critical model
      considerations.
AB  - BACKGROUND: When considering supine position and REM dependence, many studies
      refer to the traditional definition in which obstructive sleep apnea (OSA)
      severity is at least doubled in the corresponding position/sleep stage
      (Cartwright index). The lack of consideration of the time spent in that
      particular sleep situation can lead to clinical bias. PATIENTS AND METHODS: Two
      cohorts of patients with at least moderate OSA were analyzed retrospectively for
      anthropometric associations and correlations with OSA severity. One group
      consisted of 48 patients diagnosed using a polygraph, and the other group of 222
      patients underwent polysomnography. First, the conventional Cartwright index was
      used, and a modified index was later applied to integrate the relative time
      component for REM sleep and the supine position. RESULTS: Less than a fifth of
      the patients fulfilled the classic conditions for supine position or REM sleep
      dependency. There were no definitive cut-offs in the classic or modified
      Cartwright index with regard to daytime sleepiness. Both indices show there was a
      correlation between OSA severity and being overweight. CONCLUSION: The modified
      Cartwright index allowed us to identify borderline cases that were characterized
      by a very low or high amount of time spent in the supine position or REM sleep
      situation. Therapy effects that could have been biased only by varying amounts of
      time spent in the supine position could be better controlled for. Future studies
      will possibly include various other ratios besides the previously accepted 2:1
      ratio when different statistical parameters are considered, such as the reduction
      of OSA severity or therapy adherence.

PMID- 27882399
TI  - [Circadian rhythm : Influence on Epworth Sleepiness Scale score].
AB  - BACKGROUND: The Epworth Sleepiness Scale (ESS) is frequently used to determine
      daytime sleepiness in patients with sleep-disordered breathing. It is still
      unclear whether different levels of alertness induced by the circadian rhythm
      influence ESS score. OBJECTIVE: The aim of this study is to investigate the
      influence of circadian rhythm-dependent alertness on ESS performance. MATERIALS
      AND METHODS: In a monocentric prospective noninterventional observation study, 97
      patients with suspected sleep-disordered breathing were investigated with respect
      to daytime sleepiness in temporal relationship to polysomnographic examination
      and treatment. The Karolinska Sleepiness Scale (KSS) and the Stanford Sleepiness
      Scale (SSS) served as references for the detection of present sleepiness at three
      different measurement times (morning, noon, evening), prior to and following a
      diagnostic polysomnography night as well as after a continuous positive airway
      pressure (CPAP) titration night (9 measurements in total). The KSS, SSS, and ESS
      were performed at these times in a randomized order. RESULTS: The KSS and SSS
      scores revealed a circadian rhythm-dependent curve with increased sleepiness at
      noon and in the evening. Following a diagnostic polysomnography night, the scores
      were increased compared to the measurements prior to the night. After the CPAP
      titration night, sleepiness in the morning was reduced. KSS and SSS reflect the
      changes in alertness induced by the circadian rhythm. The ESS score war neither
      altered by the intra-daily nor by the inter-daily changes in the level of
      alertness. CONCLUSION: According to the present data, the ESS serves as a
      reliable instrument to detect the level of daytime sleepiness independently of
      the circadian rhythm-dependent level of alertness.

PMID- 27882402
TI  - [Diseases of connective tissue in IgG4-associated autoimmune diseases].
AB  - The IgG4-associated diseases of connective tissue are caused by allergen-mediated
      autoimmune processes. The retroperitoneum, mesentery and mediastinum as well as
      other less common localizations, such as the neck, orbit and periarticular
      connective tissue can be affected. Inflammatory fibrosis is initially dominated
      by a lymphocytic and plasma cell-rich infiltrate and later by cell-poor storiform
      fibrosis. Stenosis and occlusion of vessels, ureters and intestines can cause
      severe complications. Computed tomography (CT) and magnetic resonance imaging
      (MRI) can be implemented in the diagnostic algorithm to narrow the differential
      diagnosis, delineate the distribution of fibrosis and reveal complications.

PMID- 27882401
TI  - [Antibiotic prophylaxis for transrectal prostate biopsy].

PMID- 27882403
TI  - [Radiological dose and metadata management].
AB  - This article describes the features of management systems currently available in
      Germany for extraction, registration and evaluation of metadata from radiological
      examinations, particularly in the digital imaging and communications in medicine
      (DICOM) environment. In addition, the probable relevant developments in this area
      concerning radiation protection legislation, terminology, standardization and
      information technology are presented.

PMID- 27882404
TI  - Reduced trans-mitral A-wave velocity predicts the presence of wild-type
      transthyretin amyloidosis in elderly patients with left ventricular hypertrophy.
AB  - Wild-type transthyretin amyloidosis (ATTRwt) is often overlooked in elderly
      patients with left ventricular hypertrophy (LVH). Impaired atrial function, in
      addition to ventricular diastolic dysfunction, is one of the hallmarks of cardiac
      amyloidosis. Here, we assessed the hypothesis that atrial function evaluated by A
      velocity in pulse Doppler echocardiography is useful to differentiate ATTRwt in
      elderly patients with LVH. We analyzed 133 consecutive patients who underwent
      tissue biopsy to rule out infiltrative cardiomyopathy in our institute. We
      excluded patients younger than 50 years, without LVH (LV thickness was less than
      12 mm), with other types of cardiac amyloidosis and patients with chronic atrial
      fibrillation, and analyzed remaining 51 patients (ATTRwt: 16, non-ATTRwt: 35).
      ATTRwt patients were significantly older and had advanced heart failure compared
      with non-ATTRwt group. In echocardiography, E/A, E/e', and relative wall
      thickness was significantly higher in ATTRwt group than non-ATTRwt group. A
      velocity was significantly decreased in ATTRWT group compared with non-ATTRwt
      group (40.8 +/- 20.8 vs. 78.7 +/- 28.2 cm/s, p = 0.0001). Multivariate logistic
      analysis using eight forced inclusion models identified trans-mitral Doppler A
      wave velocity was more significant factor of cardiac amyloidosis in ATTRwt. In
      receiver operating characteristic (ROC) analysis, the area under the curve (AUC)
      for A-wave velocity in discrimination between ATTRwt and non-ATTRwt were 0.86 (CI
      0.76-0.96, p < 0.001). The cut-off value was 62.5 cm/s, and it yielded the best
      combination of sensitivity (69.7%) and specificity (87.5%) for prediction of
      amyloidosis. We concluded that reduced A-velocity predicts the presence of ATTRwt
      in elderly patients with LVH in sinus rhythm.

PMID- 27882405
TI  - Outcomes of laparoscopic surgery in pathologic T4 colon cancers compared to those
      of open surgery.
AB  - INTRODUCTION: Despite the oncologic safety of laparoscopic surgery in colon
      cancer management, laparoscopy is not regarded as a standard treatment for T4
      colon cancer. The aim of this study was to investigate the short-term and long
      term oncologic outcomes of laparoscopic surgery in patients with locally advanced
      colon cancer. MATERIAL AND METHOD: From March 2003 to June 2013, a total of 109
      consecutive patients with proven pathologic T4 colon cancer were enrolled. These
      patients were divided into the laparoscopy group (LG, n = 52) and the open group
      (OG, n = 57). Perioperative and long-term oncologic outcomes were compared
      between the two groups. RESULTS: In the LG, open conversion occurred in four
      patients (7.6%). Combined resection was less commonly performed in the LG (13.5%)
      than in the OG (36.8%, P = 0.005). Operation time was similar between the two
      groups. In the LG, blood loss (129 mL vs. 437 mL, P < 0.001) and overall
      complication rate (13.5 vs. 36.8%, P = 0.005) were lower and length of hospital
      stay was shorter (median 7 vs. 17 days, P < 0.001) than in the OG. The 5-year
      overall survival rate was 60.7% for the LG and 61.9% for the OG (P = 0.817).
      Local recurrence-free survival did not differ between the groups (88.9% in LG vs.
      88.1% in OG, P = 0.725). CONCLUSION: Considering the benefits of early recovery
      and similar oncologic outcomes, laparoscopic surgery in T4 colon cancer could be
      a viable option in selected patients.

PMID- 27882406
TI  - Bowel perforation after liver transplantation for biliary atresia: a
      retrospective study of care in the transition from children to adulthood.
AB  - PURPOSE: We evaluated the outcomes of liver transplantation (LT) in pediatric and
      adult patients with biliary atresia (BA). We focused on bowel perforation after
      LT (BPLT) as the most common surgical complication and analyzed its risk factors.
      METHODS: This was a retrospective analysis of 70 BA patients who underwent LT.
      The patients were divided into three groups according to the timing of LT: within
      the first year of age (Group A), between 1 and 12 years of age (Group B), and
      after 12 years of age (Group C). The outcomes of LT and the clinical
      presentations of BPLT were compared. The surgical variables of patients with and
      without BPLT were analyzed to assess the risk factors. RESULTS: The timing of LT
      did not affect patient survival. The incidence of BPLT was significantly higher
      in Group C. In Group C, BPLT progressed to severe peritonitis. No cases of BPLT
      associated mortality were observed. A multivariate analysis revealed that a
      prolonged operative time for LT was an independent risk factor (p = 0.03).
      CONCLUSION: The clinical course after transplantation was complicated after
      adolescence. BPLT should be strongly suspected and relaparotomy should be
      performed in a timely manner for patients undergoing LT after adolescence.

PMID- 27882408
TI  - [Evidence-based recommendations on diagnostics and therapy of axial
      spondyloarthritis : S3 guidelines of the German Society of Rheumatology (DGRh) in
      cooperation with the Association of the Scientific Medical Societies in Germany
      (AWMF)].
AB  - The clinical course of axial spondyloarthritis (SpA) is variable and
      characterized by chronic back pain and extraspinal manifestations, such as
      asymmetrical arthritis, dactylitis and enthesitis. Extra-articular manifestations
      in the eyes (anterior uveitis), skin (psoriasis) and intestines (chronic
      inflammatory bowel disease) are also frequent manifestations in patients with
      SpA. Due to the heterogeneity of disease manifestations and the partial
      concentration on structural alterations in the sacroiliac joints visible in X-ray
      images, the diagnosis is often delayed for many years. An important step in the
      direction of improved early recognition of axial SpA was establishment of the
      Assessment of SpondyloArthritis International Society (ASAS) classification
      criteria published in 2009, which focused on the initally deep-seated back pain
      and chronicity in relatively young patients as well as the importance of magnetic
      resonance imaging and HLA B 27 determination in the early stages of the disease.
      In order to achieve the foundations for an effective and timely therapy of
      affected patients, in 2014 on the initiative of the German Society of
      Rheumatology, S3 guidelines on axial SpA including Bechterew's disease and early
      forms were formulated in cooperation with other specialist societies. This
      article gives an overview of the contents of the S3 guidelines on axial SpA.

PMID- 27882407
TI  - A novel system for correcting large-scale chromosomal aberrations: ring
      chromosome correction via reprogramming into induced pluripotent stem cell
      (iPSC).
AB  - Approximately 1 in 500 newborns are born with chromosomal abnormalities that
      include trisomies, translocations, large deletions, and duplications. There is
      currently no therapeutic approach for correcting such chromosomal aberrations in
      vivo or in vitro. When we attempted to produce induced pluripotent stem cell
      (iPSC) models from patient-derived fibroblasts that contained ring chromosomes,
      we found that the ring chromosomes were eliminated and replaced by duplicated
      normal copies of chromosomes through a mechanism of uniparental isodisomy
      (Bershteyn et al. 2014, Nature 507:99). The discovery of this previously
      unforeseen system for aberrant chromosome correction during reprogramming enables
      us for the first time to model and understand this process of cell-autonomous
      correction of ring chromosomes during human patient somatic cell reprograming to
      iPSCs. This knowledge could lead to a potential therapeutic strategy to correct
      common large-scale chromosomal aberrations, termed "chromosome therapy".

PMID- 27882410
TI  - A review of recent evidence relating to sugars, insulin resistance and diabetes.
AB  - The potential impact on health of diets rich in free sugars, and particularly
      fructose, is of major concern. The focus of this review is the impact of these
      sugars on insulin resistance and obesity, and the associated risk of developing
      type 2 diabetes. Much of the concern is focussed on specific metabolic effects of
      fructose, which are argued to lead to increased fat deposition in the liver and
      skeletal muscle with subsequent insulin resistance and increased risk of
      diabetes. However, much of the evidence underpinning these arguments is based on
      animal studies involving very large intakes of the free sugars. Recent human
      studies, in the past 5 years, provide a rather different picture, with a clear
      dose response link between fructose intake and metabolic changes. In particular,
      the most marked effects are observed when a high sugars intake is accompanied by
      an excess energy intake. This does not mean that a high intake of free sugars
      does not have any detrimental impact on health, but rather that such an effect
      seems more likely to be a result of the high sugars intake increasing the chances
      of an excessive energy intake rather than it leading to a direct detrimental
      effect on metabolism.

PMID- 27882409
TI  - The pivotal role of abscisic acid signaling during transition from seed
      maturation to germination.
AB  - Seed maturation and germination are two continuous developmental processes that
      link two distinct generations in spermatophytes; the precise genetic control of
      these two processes is, therefore, crucially important for the survival of the
      next generation. Pieces of experimental evidence accumulated so far indicate that
      a concerted action of endogenous signals and environmental cues is required to
      govern these processes. Plant hormone abscisic acid (ABA) has been suggested to
      play a predominant role in directing seed maturation and maintaining seed
      dormancy under unfavorable environmental conditions until antagonized by
      gibberellins (GA) and certain environmental cues to allow the commencement of
      seed germination when environmental conditions are favorable; therefore, the
      balance of ABA and GA is a major determinant of the timing of seed germination.
      Due to the advent of new technologies and system biology approaches, molecular
      studies are beginning to draw a picture of the sophisticated genetic network that
      drives seed maturation during the past decade, though the picture is still
      incomplete and many details are missing. In this review, we summarize recent
      advances in ABA signaling pathway in the regulation of seed maturation as well as
      the transition from seed maturation to germination, and highlight the importance
      of system biology approaches in the study of seed maturation.

PMID- 27882411
TI  - Mercury Concentrations in Feathers of Adult and Nestling Osprey (Pandion
      haliaetus) from Coastal and Freshwater Environments of Florida.
AB  - We determined mercury (Hg) concentrations in feathers of osprey (Pandion
      haliaetus), both nestlings (n = 95) and adults (n = 110), across peninsular
      Florida and the Florida Keys during February-August 2014. Feathers plucked from
      nestlings, aged 3-7 weeks, contained Hg concentrations that ranged from 0.338 to
      45.79 mg/kg and averaged 6.92 +/- 7.58 mg/kg (mean +/- 1SD). Feathers shed from
      adults contained significantly higher concentrations ranging from 0.375 to 93.65
      mg/kg, with an average of 17.8 +/- 16.1 mg/kg. These levels were in the upper
      range of previously reported feather Hg concentrations of osprey and clearly show
      that Florida continues to have Hg hotspots that are elevated compared with many
      other regions. While these concentrations did not exceed levels previously
      reported in osprey from heavily Hg contaminated areas that showed no evidence of
      reproductive impairments, we cannot rule out potential individual-level effects
      to highly exposed nestlings after fledging. Mercury concentrations in nestlings
      were highest in coastal habitats of Collier and Monroe counties, where ongoing
      declines in osprey populations also have been documented.

PMID- 27882412
TI  - Impact of attention deficit hyperactivity disorder therapy on fracture risk in
      children treated in German pediatric practices.
AB  - : Two thousand eight hundred ninety-four children and adolescents treated by 243
      pediatricians were analyzed. Patients receiving attention deficit hyperactivity
      disorder (ADHD) medications were at a lower risk of fractures than patients
      without ADHD medications. The strongest impact was in the age group of 6-9 years.
      Finally, there was a significant association between therapy duration and
      fracture risk. INTRODUCTION: The aim of this study was to analyze the impact of
      ADHD therapy on fracture risk in children treated by German pediatricians.
      METHODS: Children and adolescents initially diagnosed with ADHD and fractures
      between 2010 and 2015 were identified by 243 pediatricians. In this nested case
      control study, each ADHD case with a fracture was matched (1:1) to an ADHD
      control without a fracture for age, gender, index year, and physician. In total,
      2894 individuals were available for analysis. The main outcome of the study was
      the risk of fracture as a function of ADHD therapy. Multivariate logistic
      regression models were created to determine the effect of ADHD therapy on the
      risk of fracture in the entire population and in three age-specific subgroups.
      RESULTS: Patients receiving ADHD medications were at a lower risk of fracture
      than patients without ADHD medications (OR = 0.61). The impact of ADHD therapy on
      the risk of fracture was stronger in the age group of 6-9 years (OR = 0.41) than
      in the age groups of 10-13 years (OR = 0.68) and 14-17 years (OR = 0.74).
      Finally, a significant correlation was found between therapy duration and
      fracture risk (OR = 0.71 per month). CONCLUSION: ADHD therapy was associated with
      a decrease in the risk of fracture in children and adolescents treated by German
      pediatricians.

PMID- 27882413
TI  - Double-bundle anterior cruciate ligament reconstruction is superior to single
      bundle reconstruction in terms of revision frequency: a study of 22,460 patients
      from the Swedish National Knee Ligament Register.
AB  - PURPOSE: Studies comparing single- and double-bundle anterior cruciate ligament
      (ACL) reconstructions often include a combined analysis of anatomic and non
      anatomic techniques. The purpose of this study was to compare the revision rates
      between single- and double-bundle ACL reconstructions in the Swedish National
      Knee Ligament Register with regard to surgical variables as determined by the
      anatomic ACL reconstruction scoring checklist (AARSC). METHODS: Patients from the
      Swedish National Knee Ligament Register who underwent either single- or double
      bundle ACL reconstruction with hamstring tendon autograft during the period 2007
      2014 were included. The follow-up period started with primary ACL reconstruction,
      and the outcome measure was set as revision surgery. An online questionnaire
      based on the items of the AARSC was used to determine the surgical technique
      implemented in the single-bundle procedures. These were organized into subgroups
      based on surgical variables, and the revision rates were compared with the double
      bundle ACL reconstruction. Hazard ratios (HR) with 95% confidence interval (CI)
      was calculated and adjusted for confounders by Cox regression. RESULTS: A total
      of 22,460 patients were included in the study, of which 21,846 were single-bundle
      and 614 were double-bundle ACL reconstruction. Double-bundle ACL reconstruction
      had a revision frequency of 2.0% (n = 12) and single-bundle 3.2% (n = 689).
      Single-bundle reconstruction had an increased risk of revision surgery compared
      with double-bundle [adjusted HR 1.98 (95% CI 1.12-3.51), p = 0.019]. The subgroup
      analysis showed a significantly increased risk of revision surgery in patients
      undergoing single-bundle with anatomic technique using transportal drilling
      [adjusted HR 2.51 (95% CI 1.39-4.54), p = 0.002] compared with double-bundle ACL
      reconstruction. Utilizing a more complete anatomic technique according to the
      AARSC lowered the hazard rate considerably when transportal drilling was
      performed but still resulted in significantly increased risk of revision surgery
      compared with double-bundle ACL reconstruction [adjusted HR 1.87 (95% CI 1.04
      3.38), p = 0.037]. CONCLUSIONS: Double-bundle ACL reconstruction is associated
      with a lower risk of revision surgery than single-bundle ACL reconstruction.
      Single-bundle procedures performed using transportal femoral drilling technique
      had significantly higher risk of revision surgery compared with double-bundle.
      However, a reference reconstruction with transportal drilling defined as a more
      complete anatomic reconstruction reduces the risk of revision surgery
      considerably. LEVEL OF EVIDENCE: III.

PMID- 27882414
TI  - Systemic endothelial function measured by flow-mediated dilation is impaired in
      patients with urolithiasis.
AB  - Some in vitro and animal studies have shown endothelial dysfunction in
      hyperoxaluria models indicating its role in pathogenesis of urolithiasis and
      relation to CVD. The aim of this study was to investigate endothelial function in
      patients with urolithiasis in relation to urinary stone risk factors and
      metabolic parameters. A total of 120 subjects without any known CVD (60 with
      urolithiasis and 60 healthy subjects) were included into study. Fasting blood and
      24-h urine samples were collected to study metabolic parameters (glucose and
      lipids) and urine stone risk factors (oxalate, citrate, uric acid, and calcium,
      pH). Endothelial function was assessed as flow-mediated dilation (FMD) at the
      brachial artery. Age, sex, and body mass index were similar in patients and
      controls. Of urine stone risk factors, oxalate and citrate were higher in
      patients than controls. Fasting blood glucose, total LDL cholesterol, and
      triglyceride were higher, and HDL cholesterol was lower in patients than
      controls. Although within normal limits systolic blood pressure was higher in
      patient group, patients with urolithiasis had a lower %FMD than controls. Percent
      FMD was negatively correlated with urinary oxalate/creatinine ratio (p = 0.019, r
      = -0.315), calcium/creatinine ratio (p = 0.0001, r = -0.505) age (p < 0.001, r = 
      0.694), BMI (p < 0.001, r = -0.838), total cholesterol (p < 0.001, r = -0.559),
      and triglyceride (p < 0.001, r = -0.529). Urine oxalate/creatinine ratio was
      positively correlated with age (p = 0.01, r = 0.327) and calcium/creatinine ratio
      with BMI (p = 0.001, r = 0.410). This is the first study demonstrating
      endothelial dysfunction in human subjects with urolithiasis. This indicates a
      possible predictive role of urolithiasis in future development of cardiovascular
      diseases.

PMID- 27882415
TI  - Laparoscopic Repair for Perforated Peptic Ulcer: A Retrospective Study.
AB  - BACKGROUNDS: The incidence of patients presenting with perforated peptic ulcers
      (PPU) has decreased during the last decades. At the same time, a laparoscopic
      approach to this condition has been adopted by increased number of surgeons. The
      aim of this study was to evaluate the early postoperative results of the
      laparoscopic treatment of perforated peptic ulcer performed in eight Romanian
      surgical centers with extensive experience in laparoscopic surgery. METHODS:
      Between 2009 and 2013, 297 patients with perforated peptic ulcer were operated in
      the eight centers participating in this retrospective study. The patients' charts
      were reviewed for demographics, surgical procedure, complications and short-term
      outcomes. RESULTS: Boey score of 0 was found in 122 patients (41.1%), Boey 1 in
      169 (56.9%), Boey 3 in 6 (2.0%). For 145 (48.8%) patients, primary suture repair
      was performed, in 146 (49.2%) primary suture repair with omentopexy. There were 6
      (2.0%) conversions to open surgery. The operative time was between 25 and 120
      min, with a mean of 68 min. Two (0.7%) deaths were noted. Mean hospital stay was
      5.5 days, ranges 3-25 days. Postoperative complications included: 7 (2.4%)
      superficial surgical site infections, 5 (1.6%) cardiovascular, 3 (1.0%)
      pulmonary, 2 (0.7%) duodenal leakages, 3 (1.0%) deep space infections and 1
      (0.3%) upper digestive hemorrhage. CONCLUSIONS: This study shows that the
      laparoscopic approach for PPU is feasible; the procedure is safe, with no
      increased risk of duodenal fistulae or residual intraperitoneal abscesses. We now
      consider the laparoscopic approach for PPU as the "gold standard" in patients
      with Boey score 0 or 1.

PMID- 27882417
TI  - Adrenal Injuries: Historical Facts and Modern Truths.
AB  - BACKGROUND: Prior to the advent of whole body computed tomography, injuries of
      the adrenal gland were almost exclusively identified on postmortem examinations
      and were associated with severe injury. Recent literature has continued to
      identify an association between adrenal injuries and high ISS. The purpose of
      this study was to assess the influence of adrenal trauma on ISS and mortality
      while controlling for potential confounding factors. METHODS: A 15-year
      retrospective review for all adrenal gland injuries from a Level 1 Trauma
      Center's Trauma Registry was performed. Based on the characteristics of that
      patient population, the same Trauma Registry was then queried for case-matched
      patients, and the two groups compared to assess the influence of adrenal gland
      injuries on mortality. RESULTS: Seventy-two patients with adrenal injuries were
      identified and compared to 1026 case-matched patients. The adrenal gland injury
      was not a contributing factor in any of the study group mortalities. The mean ISS
      for the adrenal gland injured group was higher than the overall Registry ISS
      (18.7 vs 10.6) but almost identical to the ISS of patients case matched for
      abdominal injuries. CONCLUSION: Case-matched analysis based on multiple clinical
      variables demonstrates that the ISS of patients with adrenal gland injuries were
      similar to the ISS of patients with other injuries to the abdominal region and
      were in fact associated with a 0.02% decrease in mortality.

PMID- 27882416
TI  - Toward More Efficient Surveillance of Barrett's Esophagus: Identification and
      Exclusion of Patients at Low Risk of Cancer.
AB  - BACKGROUND: Endoscopic surveillance of Barrett's esophagus (BE) is probably not
      cost-effective. A sub-population with BE at increased risk of high-grade
      dysplasia (HGD) or esophageal adenocarcinoma (EAC) who could be targeted for cost
      effective surveillance was sought. METHODS: The outcome for BE surveillance from
      2003 to 2012 in a structured program was reviewed. Incidence rates and incidence
      rate ratios for developing HGD or EAC were calculated. Risk stratification
      identified individuals who could be considered for exclusion from surveillance. A
      health-state transition Markov cohort model evaluated the cost-effectiveness of
      focusing on higher-risk individuals. RESULTS: During 2067 person-years of follow
      up of 640 patients, 17 individuals progressed to HGD or EAC (annual IR 0.8%).
      Individuals with columnar-lined esophagus (CLE) >=2 cm had an annual IR of 1.2%
      and >8-fold increased relative risk of HGD or EAC, compared to CLE <2 cm [IR
      0.14% (IRR 8.6, 95% CIs 4.5-12.8)]. Limiting the surveillance cohort after the
      first endoscopy to individuals with CLE >=2 cm, or dysplasia, followed by a
      further restriction after the second endoscopy-exclusion of patients without
      intestinal metaplasia-removed 296 (46%) patients, and 767 (37%) person-years from
      surveillance. Limiting surveillance to the remaining individuals reduced the
      incremental cost-effectiveness ratio from US$60,858 to US$33,807 per quality
      adjusted life year (QALY). Further restrictions were tested but failed to improve
      cost-effectiveness. CONCLUSIONS: Based on stratification of risk, the number of
      patients requiring surveillance can be reduced by at least a third. At a
      willingness-to-pay threshold of US$50,000 per QALY, surveillance of higher-risk
      individuals becomes cost-effective.

PMID- 27882418
TI  - Compliance with Guidelines of Enhanced Recovery After Surgery in Elderly Patients
      Undergoing Gastrectomy.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) aims at expediting
      postoperative recovery by implementing specific strategies in perioperative
      management. However, the tolerance to such fast-tracking protocols is under
      debate, especially in elderly patients. We aimed to investigate rate of
      compliance with the main ERAS guidelines in elderly gastrectomy patients.
      METHODS: Using data for 168 gastric cancer patients who underwent ERAS after
      gastrectomy as part of Clinical Trial NCT01653496, we calculated the rates of
      compliance with nine main ERAS guidelines and compared the compliance rates of
      elderly (>=70 years) and non-elderly (<70 years) patients. Surgical outcomes and
      fulfillment of criteria for postoperative discharge were also compared. RESULTS:
      The study included 55 elderly and 113 non-elderly patients. There were no
      significant differences between these groups of patients with respect to
      operative techniques and tumor stage. Except for restricted intravenous fluid
      administration, the patients in both groups showed very high compliance rates
      (>90%) for every ERAS guideline. Notably, the overall compliance rates did not
      differ significantly between the groups. Postoperatively, the mean time to
      fulfillment of discharge criteria was slightly longer for elderly patients (4.7
      vs. 4.2 days, p = 0.005), but there were no significant differences between the
      groups with respect to the incidence of postoperative complications, length of
      hospitalization, and readmission rate. CONCLUSION: Compliance of the medically
      and physically fit elderly patients with the main ERAS guidelines is comparable
      to that of non-elderly patients, and such protocols can be safely applied to
      elderly patients without significant modification.

PMID- 27882419
TI  - Pleural Effusion After Hepatectomy for Hepatocellular Carcinoma: Risk Factor
      Analyses and Its Impact on Oncological Outcomes.
AB  - BACKGROUND: Although posthepatectomy pleural effusion (PHPE) is a commonly
      observed phenomenon, its precise etiology and the impact of its emergence on
      oncological outcomes have still unknown. The aim of the current study was to
      retrospectively investigate risk factors for PHPE and its impact on oncological
      outcomes of hepatocellular carcinoma (HCC). METHODS: Medical records of 330
      patients who underwent primary curative hepatectomy for HCC were reviewed. All
      330 patients had CT around day 7 after hepatectomy, and the emergence of PHPE on
      CT was examined. Presumed 38 risk factors for the emergence of PHPE and already
      known 9 risk factors together with PHPE for HCC recurrence and patient death
      after hepatectomy were analyzed. RESULTS: The overall incidence of PHPE was 54.5%
      (180/330). One hundred seventy-nine and 38 out of the 180 patients had right
      sided PHPE and left-sided PHPE, respectively. The independent risk factors for
      right-sided PHPE were hepatitis B or C back ground, lower preoperative white
      blood cell count, larger intraoperative blood loss, longer operation time,
      subcostal incision, and longer total inflow occlusion time, while the only
      independent risk factor for left-sided PHPE was longer operation time. Left-sided
      PHPE was testified to be one of the independent risk factors not only for HCC
      recurrence but also for patient death. CONCLUSIONS: Although the cause of PHPE
      after hepatectomy might be multifactorial, the emergence of left-sided PHPE is a
      portent of worse oncological outcomes after curative hepatectomy for HCC and
      patients with left-sided PHPE need close follow-ups.

PMID- 27882420
TI  - The Clinical Indications for Limited Surgery of Intraductal Papillary Mucinous
      Neoplasms of the Pancreas.
AB  - BACKGROUND: There are many reports about limited surgery for intraductal
      papillary mucinous neoplasms (IPMNs) of the pancreas. However, there is no
      consensus on limited surgery for IPMNs. The primary objective of this study was
      to define the clinical indications for limited surgery for IPMNs. METHODS: The
      data of 98 patients who underwent curative resections for IPMN were
      retrospectively analyzed. IPMNs were classified into four different pathological
      grades: low-grade dysplasia (LGD), intermediate-grade dysplasia (IGD), high-grade
      dysplasia (HGD), and invasive carcinoma (Inv-IPMN). Inv-IPMNs were divided into
      T1a, T1b, and T1c or over T1c (>=T1c). Based on preoperative radiological
      findings, IPMNs were stratified into the three groups using the 2012
      International Consensus Guidelines: worrisome features, high-risk stigmata (HRS),
      and others. RESULTS: There were no positive lymph node cases and no recurrent
      cases of LGDs, IGDs, and HGDs. On the other hand, positive lymph node cases in
      T1a, T1b, and >=T1c were seen in 37.5, 20, and 22.2% of cases, respectively. The
      recurrence rates of T1a, T1b, and >=T1c were 50, 40, and 55.6%, respectively. Of
      the HRS cases, 30 (73.2%) were malignant and 25 (61%) were Inv-IPMN. HRS showed
      sensitivity of 92.6%, specificity of 77.5%, and accuracy of 81.6% to identify Inv
      IPMN by preoperative imaging. CONCLUSIONS: Limited surgery such as parenchyma
      sparing pancreatectomy should be avoided for all cases of Inv-IPMNs, because
      every Inv-IPMN including T1a has the potential for lymph node metastasis and
      recurrence. HRS had high preoperative diagnostic ability for predicting Inv-IPMN.
      For cases that meet HRS criteria, pancreatectomy with lymphadenectomy is needed,
      and limited surgery should be withheld.

PMID- 27882421
TI  - Invasive meningococcal disease-induced myocarditis in critically ill adult
      patients: initial presentation and long-term outcome.

PMID- 27882422
TI  - Predictors of Pharmacological Therapy of Ectopic Atrial Tachycardia in Children.
AB  - Ectopic atrial tachycardia (EAT) is a relatively common type of supraventricular
      tachycardia in the pediatric population, and it can be resistant to
      antiarrhythmic drugs and lead to tachycardia-induced cardiomyopathy (TIC) if not
      properly managed. The purpose of this study was to determine the predictors of
      the response to pharmacological therapy in children with EAT. From January 2009
      to April 2014, 115 children were admitted to our hospital with a diagnosis of EAT
      and placed on antiarrhythmic drugs. We examined the clinical history, response to
      therapy, and follow-up of the children. The incidence of TIC secondary to EAT was
      22.6% (n = 26) in children. Incessant EAT accounted for 44.3% of all patients.
      Control of EAT with antiarrhythmic therapy was achieved in 73.9% (n = 85) of the
      children. The combination of sotalol and propafenone performed well in
      controlling EAT in children [complete control in 35 (49.3%) of 71]. The mean time
      of conversion to sinus rhythm was 24 days, and the mean duration of therapy was
      11 months in children with resolution. Multivariate predictors of the control of
      EAT were age at presentation (OR 0.289, P = 0.038) and tachycardia type (OR
      0.276, P = 0.006). TIC occurs in 22.6% of children with EAT. Incessant EAT is
      more frequently complicated by TIC. Independent factors associated with a good
      response to pharmacological therapy include a younger age at presentation and non
      incessant tachycardia in children with EAT.

PMID- 27882423
TI  - Cardio-Ankle Vascular Index (CAVI) and Plasma Transforming Growth Factor-beta1
      (TGF-beta1) Level Correlate with Aortopathy in Adults with Repaired Tetralogy of
      Fallot.
AB  - It is challenging to evaluate aortopathy in congenital heart disease using
      conventional investigations such as brachial-ankle pulse wave velocity (baPWV).
      Therefore, we evaluated the cardio-ankle vascular index (CAVI), a dimension of
      the ascending aorta and plasma transforming growth factor-beta1 (TGF-beta1)
      level, in order to find novel noninvasive parameters of aortopathy in adults with
      repaired tetralogy of Fallot (TOF). Prospectively, we enrolled 42 consecutive
      adults with TOF (28 patients with repaired TOF were not on ARB, 8 patients with
      repaired TOF on ARB, 6 patients with no repair or only palliative repair) and 20
      age-matched healthy controls. We measured CAVI, baPWV, plasma TGF-beta1 level and
      a diameter of the ascending aorta using echocardiography. The mean age of
      repaired TOF without ARB were 31.9 +/- 9.1 years. An aortic diameter of the
      ascending aorta, CAVI, and plasma TGF-beta1 level were significantly higher in
      repaired TOF without ARB than those in controls, whereas baPWV did not differ. On
      a univariate analysis, CAVI, plasma TGF-beta1 level and Rastelli procedure were
      important factors for an aortic diameter of the ascending aorta (r = 0.56, P <
      0.01, r = 0.59, P < 0.01, r = 0.39, P < 0.05, respectively) in this population.
      There was no significant correlation with age, baPWV, NT-pro brain natriuretic
      peptide (BNP), repair age, shunt duration, aortic regurgitation or right aortic
      arch. On the other hand, patients with unrepaired or palliative TOF, who had
      obvious volume overload, showed no significant correlation with CAVI, baPWV or
      plasma TGF-beta1 level. CAVI and plasma TGF-beta1 level, not baPWV, correlate to
      aortopathy in adults with repaired TOF.

PMID- 27882424
TI  - Influence of Transplant Center Procedural Volume on Survival Outcomes of Heart
      Transplantation for Children Bridged with Mechanical Circulatory Support.
AB  - Transplant center expertise improves survival after heart transplant (HTx) but it
      is unknown whether center expertise ameliorates risk associated with mechanical
      circulatory support (MCS) bridge to transplantation. This study investigated
      whether center HTx volume reduced survival disparities among pediatric HTx
      patients bridged with extracorporeal membrane oxygenation (ECMO), left
      ventricular assist device (LVAD), or no MCS. Patients <=18 years of age receiving
      first-time HTx between 2005 and 2015 were identified in the United Network of
      Organ Sharing registry. Center volume was the total number of HTx during the
      study period, classified into tertiles. The primary outcome was 1 year post
      transplant survival, and MCS type was interacted with center volume in Cox
      proportional hazards regression. The study cohort included 4131 patients, of whom
      719 were supported with LVAD and 230 with ECMO. In small centers (<=133 HTx over
      study period), patients bridged with ECMO had increased post-transplant mortality
      hazard compared to patients bridged with LVAD (HR 0.29, 95% CI 0.12, 0.71; p =
      0.006) and patients with no MCS (HR 0.33, 95% CI 0.19, 0.57; p < 0.001).
      Interactions of MCS type with medium or large center volume were not
      statistically significant, and the same differences in survival by MCS type were
      observed in medium- or large-volume centers (136-208 or >=214 HTx over the study
      period). Post-HTx survival disadvantage of pediatric patients bridged with ECMO
      persisted regardless of transplant program volume. The role of institutional ECMO
      expertise outside the transplant setting for improving outcomes of ECMO bridge to
      HTx should be explored.

PMID- 27882425
TI  - Assessment of regional emphysema, air-trapping and Xenon-ventilation using dual
      energy computed tomography in chronic obstructive pulmonary disease patients.
AB  - OBJECTIVES: To compare the parenchymal attenuation change between
      inspiration/expiration CTs with dynamic ventilation change between xenon wash-in
      (WI) inspiration and wash-out (WO) expiration CTs. METHODS: 52 prospectively
      enrolled COPD patients underwent xenon ventilation dual-energy CT during WI and
      WO periods and pulmonary function tests (PFTs). The parenchymal attenuation
      parameters (emphysema index (EI), gas-trapping index (GTI) and air-trapping index
      (ATI)) and xenon ventilation parameters (xenon in WI (Xe-WI), xenon in WO (Xe-WO)
      and xenon dynamic (Xe-Dyna)) of whole lung and three divided areas (emphysema,
      hyperinflation and normal) were calculated on virtual non-contrast images and
      ventilation images. Pearson correlation, linear regression analysis and one-way
      ANOVA were performed. RESULTS: EI, GTI and ATI showed a significant correlation
      with Xe-WI, Xe-WO and Xe-Dyna (EI R = -.744, -.562, -.737; GTI R = -.621, -.442, 
      .629; ATI R = -.600, -.421, -.610, respectively, p < 0.01). All CT parameters
      showed significant correlation with PFTs except forced vital capacity (FVC).
      There was a significant difference in GTI, ATI and Xe-Dyna in each lung area (p <
      0.01). CONCLUSIONS: The parenchymal attenuation change between
      inspiration/expiration CTs and xenon dynamic change between xenon WI- and WO-CTs
      correlate significantly. There are alterations in the dynamics of xenon
      ventilation between areas of emphysema. KEY POINTS: * The xenon ventilation
      change correlates with the parenchymal attenuation change. * The xenon
      ventilation change shows the difference between three lung areas. * The
      combination of attenuation and xenon can predict more accurate PFTs.

PMID- 27882426
TI  - Dual-energy CT of the brain: Comparison between DECT angiography-derived virtual
      unenhanced images and true unenhanced images in the detection of intracranial
      haemorrhage.
AB  - OBJECTIVE: To evaluate the diagnostic performance of virtual non-contrast (VNC)
      images in detecting intracranial haemorrhages (ICHs). METHODS: Sixty-seven
      consecutive patients with and 67 without ICH who underwent unenhanced brain CT
      and DECT angiography were included. Two radiologists independently evaluated VNC
      and true non-contrast (TNC) images for ICH presence and type. Inter-observer
      agreement for VNC and TNC image evaluation was calculated. Sensitivity and
      specificity of VNC images for ICH detection were calculated using Fisher's exact
      test. VNC and TNC images were compared for ICH extent (qualitatively and
      quantitatively) and conspicuity assessment. RESULTS: On TNC images 116 different
      haemorrhages were detected in 67 patients. Inter-observer agreement ranged from
      0.98-1.00 for TNC images and from 0.86-1.00 for VNC images. VNC sensitivity
      ranged from 0.90-1, according to the different ICH types, and specificity from
      0.97-1. Qualitatively, ICH extent was underestimated on VNC images in 11.9% of
      cases. Haemorrhage volume did not show statistically significant differences
      between VNC and TNC images. Mean haemorrhage conspicuity was significantly lower
      on VNC images than on TNC images for both readers (p < 0.001). CONCLUSION: VNC
      images are accurate for ICH detection. Haemorrhages are less conspicuous on VNC
      images and their extent may be underestimated. KEY POINTS: * VNC images represent
      a reproducible tool for detecting ICH. * ICH can be identified on VNC images with
      high sensitivity and specificity. * Intracranial haemorrhages are less
      conspicuous on VNC images than on TNC images. * Intracranial haemorrhages extent
      may be underestimated on VNC images.

PMID- 27882427
TI  - Improved MDCT monitoring of pelvic myeloma bone disease through the use of a
      novel longitudinal bone subtraction post-processing algorithm.
AB  - PURPOSE: To evaluate the diagnostic performance of a novel CT post-processing
      software that generates subtraction maps of baseline and follow-up CT
      examinations in the course of myeloma bone lesions. MATERIALS AND METHODS: This
      study included 61 consecutive myeloma patients who underwent repeated whole-body
      reduced-dose MDCT at our institution between November 2013 and June 2015. CT
      subtraction maps classified a progressive disease (PD) vs. stable disease
      (SD)/remission. Bone subtraction maps (BSMs) only and in combination with 1-mm
      (BSM+) source images were compared with 5-mm axial/MPR scans. RESULTS:
      Haematological response categories at follow-up were: complete remission (n = 9),
      very good partial remission (n = 2), partial remission (n = 17) and SDh (n = 19)
      vs. PDh (n = 14). Five-millimetre CT scan yielded PD (n = 14) and SD/remission (n
      = 47) whereas bone subtraction + 1-mm axial scans (BSM+) reading resulted in PD
      (n = 18) and SD/remission (n = 43). Sensitivity/ specificity/accuracy for 5-mm/1
      mm/BSM(alone)/BSM + in "lesion-by-lesion" reading was 89.4 %/98.9 %/98.3 %/ 99.5
      %; 69.1 %/96.9 %/72 %/92.1 % and 83.8 %/98.4 %/92.1 %/98.3 %, respectively. The
      use of BSM+ resulted in a change of response classification in 9.8 % patients (n
      = 6) from SD to PD. CONCLUSION: BSM reading is more accurate for monitoring
      myeloma compared to axial scans whereas BSM+ yields similar results with 1-mm
      reading (gold standard) but by significantly reduced reading time. KEY POINTS: *
      CT evaluation of myeloma bone disease using a longitudinal bone subtraction post
      processing algorithm. * Bone subtraction post-processing algorithm is more
      accurate for assessment of therapy. * Bone subtraction allowed improved and more
      efficient detection of myeloma bone lesions. * Post-processing tool demonstrating
      a change in response classification in 9.8 % patients (all showing PD). * Reading
      time could be substantially shortened as compared to regular CT assessment.

PMID- 27882428
TI  - Progression of noncalcified and calcified coronary plaque by CT angiography in
      SLE.
AB  - Premature coronary artery disease remains the major cause of late death in
      systemic lupus erythematosus (SLE). Coronary artery calcium (CAC) represents an
      advanced stage of atherosclerosis, whereas noncalcified coronary atherosclerotic
      plaque (NCP) typically is more prone to trigger acute coronary events. The aim of
      this study was to assess the stability of NCP over time and identify factors
      associated with changes in NCP in patients with SLE. CT coronary angiography and
      calcium scanning were performed at baseline and follow-up in thirty-six SLE
      patients. Duration between baseline and follow-up NCP assessment ranged from 2 to
      8 years. CAC was quantified by the Agatston score and classified as none, low (1
      99), moderate (100-299) or high calcium score (300 and above). NCP was quantified
      based on a previously validated score and classified as none, low (<0.5) or high
      (0.5+). SLE disease activity was quantified using the SELENA-SLEDAI and physician
      global assessment indices. To assess the association between quantitative
      clinical variables and changes in NCP, adjusting for time, we used linear
      regression models. The group of 36 SLE patients were 75% females, 75% Caucasians,
      17% African-Americans, 8% other ethnicities. The mean age of patients was 46.6
      years. For NCP, 17/36 (47%) of the patients switched qualitative NCP class (none,
      low, high) between baseline and follow-up, whereas for CAC only 3/35 (9%)
      switched qualitative class. Increasing years between assessments were associated
      with an increase in NCP (P = 0.038). The proportion of time on immunosuppressants
      was associated with a decrease in NCP (P = 0.06). Calcified coronary plaque
      levels remained relatively stable over a period of 2-8 years. Noncalcified
      coronary plaque levels were more variable. Use of immunosuppressive drugs
      appeared to be protective against noncalcified coronary plaque progression.

PMID- 27882429
TI  - Endovascular Management of Recurrent Spontaneous Hemarthrosis After Arthroplasty.
AB  - PURPOSE: Recurrent spontaneous hemarthrosis is an infrequent but debilitating
      late complication of joint replacement, affecting up to 1.6% of patients with
      arthroplasty of the affected joint. Repeated episodes of bleeding result in an
      inflammatory cascade that further propagates bleeding events. Open and
      arthroscopic synovectomy are often performed when conservative treatments fail.
      Transarterial embolization is increasingly utilized as a less invasive option;
      however, its role is not widely established. We performed a systematic literature
      review to report the safety and efficacy of transarterial embolization in
      treating recurrent hemarthrosis in the setting of prior arthroplasty. MATERIALS
      AND METHODS: A systematic review was conducted in accordance with the Preferred
      Reporting Items for Systematic Review and Meta-Analysis guidelines. A structured
      search was performed in PubMed, Web of Science, Embase, and SCOPUS databases of
      patients undergoing embolization for recurrent hemarthrosis after arthroplasty.
      Patients immediately post-operative, those embolized at first bleeding episode,
      and those with hemophilia were excluded. Demographic data, clinical information,
      angiographic findings, treatment, and outcomes were tabulated. RESULTS: The
      search identified 119 titles of which 24 were deemed relevant, comprising 91
      patients undergoing 99 embolization procedures. Mean time from prosthesis
      implantation was 32.2 months. Technical success was 99%. Mean follow-up time was
      24.9 months. There were 10 recurrences (10%). Two cases were complicated by joint
      infection requiring arthroplasty revision. CONCLUSIONS: Transarterial
      embolization for recurrent spontaneous hemarthrosis may be safe and effective in
      patients having undergone arthroplasty of the affected joint.

PMID- 27882432
TI  - Microclimatic conditions of Lasius flavus ant mounds.
AB  - Like other organisms, ants require suitable microclimatic conditions for their
      development. Thus, ant species inhabiting colder climates build nest mounds that
      rise above the soil surface, presumably to obtain heating from solar radiation.
      Although some ant species construct mounds of organic materials, which generate
      substantial heat due to microbial metabolism, Lasius flavus mounds consists
      mostly of soil, not organic material. The use of artificial shading in the
      current study demonstrated that L. flavus depends on direct solar radiation to
      regulate the temperature in its mound-like nests. Temperatures were much lower in
      shaded mounds than in unshaded mounds and were likely low enough in shaded mounds
      to reduce ant development and reproduction. In areas where L. flavus and similar
      ants are undesirable, they might be managed by shading.

PMID- 27882430
TI  - Identification of cardiovascular risk factors associated with bone marrow cell
      subsets in patients with STEMI: a biorepository evaluation from the CCTRN TIME
      and LateTIME clinical trials.
AB  - Autologous bone marrow mononuclear cell (BM-MNC) therapy for patients with ST
      segment elevation myocardial infarction (STEMI) has produced inconsistent
      results, possibly due to BM-MNC product heterogeneity. Patient-specific
      cardiovascular risk factors (CRFs) may contribute to variations in BM-MNC
      composition. We sought to identify associations between BM-MNC subset frequencies
      and specific CRFs in STEMI patients. Bone marrow was collected from 191 STEMI
      patients enrolled in the CCTRN TIME and LateTIME trials. Relationships between BM
      MNC subsets and CRFs were determined with multivariate analyses. An assessment of
      CRFs showed that hyperlipidemia and hypertension were associated with a higher
      frequency of CD11b+ cells (P = 0.045 and P = 0.016, respectively). In addition,
      we found that females had lower frequencies of CD11b+ (P = 0.018) and CD45+CD14+
      (P = 0.028) cells than males, age was inversely associated with the frequency of
      CD45+CD31+ cells (P = 0.001), smoking was associated with a decreased frequency
      of CD45+CD31+ cells (P = 0.013), glucose level was positively associated with the
      frequency of CD45+CD3+ cells, and creatinine level (an indicator of renal
      function) was inversely associated with the frequency of CD45+CD3+ cells (P =
      0.015). In conclusion, the frequencies of monocytic, lymphocytic, and angiogenic
      BM-MNCs varied in relation to patients' CRFs. These phenotypic variations may
      affect cell therapy outcomes and might be an important consideration when
      selecting patients for and reviewing results from autologous cell therapy trials.

PMID- 27882433
TI  - Reply to communications by Fu et al. international journal of biometeorology.
AB  - Temperature sensitivity of plant phenology (ST) is a determining factor of as to
      what degree climate change impacts on plant species. Fu et al . (Int J
      Biometeorol 60:1611-1613, 2016) claimed that long long-term linear trends mask
      phenological shifts. However, the decreased and increased ST was both found in
      warming scenarios. The conceptual scheme telling the nonlinear relationship
      between spring temperature and leaf unfolding date proposed by Fu et al . (Int J
      Biometeorol 60:1611-1613, 2016) cannot be supported by observation data across
      Europe. Therefore, linking declined ST to climate warming is misleading, and
      future ST changes are more uncertain than they suggested.

PMID- 27882431
TI  - Diagnostic value of conventional chest radiography in intrathoracic goiters
      retrospective analysis of 2570 patients.
AB  - PURPOSE: Since intrathoracic goiters (IG), either cervico-mediastinal goiters
      (CMGs) or mediastinal nodules (MNs), can lead to sternotomies and/or evitable
      reoperations, their detection is mandatory before thyroid surgery. A systematic
      screening by CT scan or MRI is not conceivable because of their expensiveness. We
      tested if conventional chest radiography (CCR) could remain a good screening tool
      for IG before thyroid surgery. METHODS: In this retrospective study (2554
      patients), CCR usefulness was evaluated in relation with patients' complaints,
      clinical examination, neck US, and anatomical and surgical findings. RESULTS:
      CMGs (n = 67) and MNs (n = 42) were symptomatic in 10 and 5 patients,
      respectively. Clinical examination or neck US suspected their existence in 25 and
      13 and 45 and 17 patients, respectively. Among the 50 IG detected by CCR (42 CMGs
      and 8 MNs), 4 CMGs and 2 MNs were missed by clinical examination or neck US. CCR
      failed to detect IG in 59 patients (54%): 25 CMGs (37%) and 34 MNs (80%). Twenty
      eight IG (9 CMGs and 19 MNs) were discovered during surgery. CCR resulted in
      false positive in 88 out of 2445 patients (3.5%). CCR potentially avoided
      reoperation in two patients (a maximum saving of 6160 ?, whereas the total cost
      of CCR was 54,895 ?). CONCLUSIONS: CCR should not be used routinely for the
      preoperative detection of IG. Surgeons should preferably use clinical examination
      or neck US and directly perform CT scan when a mediastinal extension is
      suspected.

PMID- 27882434
TI  - New locality record for Haplorchoides mehrai and possible interactions with
      Opisthorchis viverrini metacercariae in cyprinid fishes in Northeast Thailand.
AB  - Metacercariae of Opisthorchis viverrini, a carcinogenic liver fluke, and
      Haplorchoides sp., a trematode maturing in catfish, are commonly found in
      cyprinid fish, the second intermediate hosts of both flukes. However, the
      specific identity of Haplorchoides sp. in Thailand and a precise assessment of
      the effects of co-infections with O. viverrini have never been clarified.
      Therefore, we aimed to identify the species of Haplorchoides and to investigate
      possible interactions of the two trematode species in cyprinid fishes. Based on
      the morphology and morphometry of the cercaria, metacercaria, and adult stages,
      the Haplorchoides species found was identified as Haplorchoides mehrai Pande and
      Shukla 1976. Thailand is formally recorded as a new locality for H. mehrai, where
      naturally infected hosts include the snail Melanoides tuberculata (first
      intermediate host), the cyprinid fishes Hampala dispar, Cyclocheilichthys apogon,
      Puntius leiacanthus, Labiobarbus burmanicus, and Cirrhina jullieni (second
      intermediate hosts), and a catfish, Mystus nemurus (definitive host). The co
      infection rates of O. viverrini and H. mehrai were significantly associated with
      fish species and fish body region (P < 0.001), with an overall significantly
      higher average intensity of H. mehrai (126.26 metacercariae/fish) than that of O.
      viverrini (18.02 metacercariae/fish). Further work is required to demonstrate the
      extent and mechanisms of possible interactions between these trematode species in
      the fish host. These data may provide a better understanding of O. viverrini
      transmission dynamics, and help design integrated control interventions.

PMID- 27882436
TI  - A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits
      tumor cell invasion and potentiates the apoptotic effect of TNFalpha by
      abrogating NF-kappaB activation cascade.
AB  - Condensed-bicyclic 4,6-substituted1,2,4-triazolo-1,3,4-thiadiazole derivatives
      (CBTT) have been shown to possess a wide spectrum of pharmacological activities.
      In this study, several novel CBTT derivatives were synthesized and investigated
      for their possible role as anti-neoplastic agents. The anti-proliferative effect
      of various CBTT derivatives was analyzed against tumor cell lines by (3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. One of the
      potential CBTT derivative, 5-(3-(2,3-dichlorophenyl)-[1,2,4]triazolo[3,4
      b][1,3,4]thiadiazol-6-yl)flurobenzonitrile (DTTF) was found to be the most potent
      against cervical cancer SiHa cells and exhibited minimal effect against normal
      cells. Molecular docking analysis indicated that transcription factor NF-kappaB
      was one of the potential molecular targets modulated by DTTF. Specifically, the
      drug blocked the TNFalpha-induced phosphorylation of upstream IkappaBalpha kinase
      in a time-dependent manner leading to the suppression of NF-kappaB activation and
      nuclear translocation. DTTF also potentiated the apoptotic effect of TNFalpha, as
      well as significantly inhibited migration and invasion of tumor cells. Overall,
      these findings indicate a potential novel role and mechanism(s) of action of DTTF
      as an anticancer agent against diverse malignancies.

PMID- 27882435
TI  - A new anatomical classification of the bronchial arteries based on the spatial
      relationships to the esophagus and the tracheobronchus.
AB  - PURPOSE: To reveal the patterns of the mediastinal course of the bronchial
      arteries (BAs). METHODS: The BAs were dissected to determine the positional
      relationships of their mediastinal courses with the tracheobronchus and the
      esophagus in 72 adult cadavers. RESULTS: The mediastinal courses of the 227 BAs
      found in this study were classified into 4 types. There were 61 and 163 BAs
      passing the right side (Type I) and the left side (Type II reaching dorsal
      surface (n = 98), or Type III reaching ventral surface (n = 65) of the
      tracheobronchus) of the esophagus, respectively. Three BAs originated from the
      subclavian artery (Type IV). All Type I BAs were right BAs, whereas 91.8% of the
      Type II BAs were left BAs. However, 43.1 and 56.9% of the Type III BAs were the
      right and left BAs, respectively. CONCLUSION: The classification of the
      mediastinal course of the BAs determined by the spatial relationships to the
      tracheobronchus and the esophagus may be clinically useful, because each category
      of this classification can be determined during esophagectomy and indicates
      whether the BA is a right or left BA.

PMID- 27882437
TI  - Cavernous sinus syndrome due to neurosarcoidosis in adolescence: a diagnosis not
      to be missed.

PMID- 27882439
TI  - Obstetric and perinatal outcome of babies born from sperm selected by MACS from a
      randomized controlled trial.
AB  - PURPOSE: The purpose of this study is to assess outcomes after magnetic-activated
      cell sorting (MACS) technology on obstetric and perinatal outcomes compared with
      those achieved after swim up from randomized controlled trial. METHODS: This is a
      two-arm, unicentric, prospective, randomized, and triple-blinded trial and has a
      total of 237 infertile couples, between October 2010 and January 2013. A total of
      65 and 66 newborns from MACS and control group, respectively, were described.
      RESULTS: MACS had no clinically relevant adverse effects on obstetric and
      perinatal outcomes. No differences were found for obstetric problems including
      premature rupture of membranes 6.1% (CI95% 0-12.8) vs. 5.9% (CI95% 0-12.4), 1st
      trimester bleeding 28.6% (CI95% 15.9-41.2) vs. 23.5% (CI95% 11.9-35.1), invasive
      procedures as amniocentesis 2.0% (CI95% 0-5.9) vs. 3.9% (CI95% 0-9.2), diabetes
      14.3% (CI95% 4.5-24.1) vs. 9.8% (CI95% 1.6-17.9), anemia 6.1% (CI95% 0-12.8) vs.
      5.9%(CI95% 0-12.4), 2nd and 3rd trimesters 10.2% (CI95% 1.7-18.7) vs. 5.9% (CI95%
      0-12.4), urinary tract infection 8.2% (CI95% 0.5-15.9) vs. 3.9% (CI95% 0-9.2),
      pregnancy-induced hypertension 6.1% (CI95% 0-12.8) vs. 15.7% (CI95% 5.7-25.7),
      birth weight (g) 2684.10 (CI95% 2499.48-2868.72) vs. 2676.12 (CI95% 2499.02
      2852.21), neonatal height (cm) 48.3 (CI95% 47.1-49.4) vs. 46.5 (CI95% 44.6-48.4),
      and gestational cholestasis 0%(CI95% 0-0) vs. 3.9% (CI95% 0-9.2), respectively,
      in MACS group compared with control group. CONCLUSIONS: Our data suggest that
      MACS technology does not increase or decrease Powered by Editorial Manager(r) and
      ProduXion Manager(r) from Aries Systems Corporation adverse obstetric and
      perinatal outcomes in children conceived when this technology was performed,
      being the largest randomized control trial with live birth reported results with
      MACS.

PMID- 27882438
TI  - Histochemical examination of systemic administration of eldecalcitol combined
      with guided bone regeneration for bone defect restoration in rats.
AB  - The aim of this experiment was to elucidate the histological alterations after
      systemic administration of eldecalcitol (ELD) combined with guided bone
      regeneration during the restoration of bone defect healing in rats. The femurs of
      8-week-old Wister rats were used to generate bone defect models. The defect was
      covered with a collagen membrane, and ELD group was administrated with
      eldecalcitol (50 ng/kg body weight) intragastrically once every other day. Femora
      were harvested at 1, 2, 4 and 8 weeks post-surgery. Decalcify tissue slices were
      made and used for histological and immunohistochemical examination. Bone
      biomarkers of RANKL, OPG and osteocalcin (OCN) were detected by western blot. The
      results revealed that the system administration of ELD could improve new bone
      formation demonstrated by the increased bone volume/tissue volume ratio and
      accelerated mineralization. ELD suppressed osteoclastic bone resorption by
      reducing the number of osteoclasts, decreasing the expression of cathepsin-K and
      the ratio of RANKL/OPG at the early stage of bone defect restoration (1 and 2
      weeks) and upregulating OCN expression at the later stage of bone defect healing
      (4 and 8 weeks). These data suggested that systemic administration of
      eldecalcitol accelerated bone formation and promoted bone maturation by
      decreasing bone resorption and promoting bone mineralization during bone defect
      restoration.

PMID- 27882440
TI  - Hemodynamic changes in a middle cerebral artery aneurysm at follow-up times
      before and after its rupture: a case report and a review of the literature.
AB  - Hemodynamic parameters play a significant role in the development of cerebral
      aneurysms. Parameters such as wall shear stress (WSS) or velocity could change in
      time and may contribute to aneurysm growth and rupture. However, the hemodynamic
      changes at the rupture location remain unclear because it is difficult to obtain
      data prior to rupture. We analyzed a case of a ruptured middle cerebral artery
      (MCA) aneurysm for which we acquired imaging data at three time points, including
      at rupture. A patient with an observed MCA aneurysm was admitted to the emergency
      department with clinical symptoms of a subarachnoid hemorrhage. During three
      dimensional (3D) digital subtraction angiography (DSA), the aneurysm ruptured
      again. Imaging data from two visits before rupture and this 3D DSA images at the
      moment of rupture were acquired, and computational fluid dynamic (CFD)
      simulations were performed. Results were used to describe the time-dependent
      changes of the hemodynamic variables associated with rupture. Time-dependent
      hemodynamic changes at the rupture location were characterized by decreased WSS
      and flow velocity magnitude. The impingement jet in the dome changed its position
      in time and the impingement area at follow-up moved near the rupture location.
      The results suggest that the increased WSS on the dome and increased low wall
      shear stress area (LSA) and decreased WSS on the daughter bleb with slower flow
      and slow vortex may be associated with rupture. CFD performed during the follow
      up period may be part of diagnostic tools used to determine the risk of aneurysm
      rupture.

PMID- 27882441
TI  - Regioselective synthesis and biological studies of novel 1-aryl-3, 5-bis (het)
      aryl pyrazole derivatives as potential antiproliferative agents.
AB  - Pyrazole moiety represents an important category of heterocyclic compound in
      pharmaceutical and medicinal chemistry. The novel 1-aryl-3, 5-bis (het) aryl
      pyrazole derivatives were synthesized with complementary regioselectivity. The
      chemical structures were confirmed by IR, 1H NMR, 13C NMR, and mass spectral
      analysis. The chemical entities were screened in various cancer cell lines to
      assess their cell viability activity. Results showed that the compound 3-(1-(4
      bromophenyl)-5-phenyl-1H-pyrazol-3-yl) pyridine (5d) possessed maximum cytotoxic
      effect against breast cancer and leukemic cells. The cytotoxicity was confirmed
      by live-dead cell assay and cell cycle analysis. Mitochondrial membrane
      potential, Annexin V-FITC staining, DNA fragmentation, Hoechst staining, and
      western blot assays revealed the ability of compound 5d to induce cell death by
      activating apoptosis in cancer cells. Thus, the present study demonstrates that
      compound 5d could be an attractive chemical entity for the development of small
      molecule inhibitors for treatment of leukemia and breast cancer.

PMID- 27882442
TI  - The effects of zofenopril on cardiac function and pro-oxidative parameters in the
      streptozotocin-induced diabetic rat heart.
AB  - Diabetes mellitus is a chronic condition that continues to increase in both
      incidence and prevalence. Renin-Angiotensin-Aldosterone System is one of the main
      modulators of chronic hyperglycaemia and, thus, its influence on tissues.
      Hyperglycaemia-induced oxidative stress is an important factor in diabetic
      cardiomyopathy. The present study was carried out on 24 adult male Wistar albino
      rats (8-week-old and with body masses of 190 +/- 10 g). We evaluated the
      influence of acute administration of zofenopril on ex vivo myocardial function
      from rats with streptozotocin-induced diabetes mellitus, with a special emphasis
      on cardiodynamic and oxidative stress parameters in diabetic rat hearts. Rats
      were divided randomly into two groups (12 animals per group): control non
      diabetic animals (C) were healthy rats perfused with 1.5 uM of zofenopril, and
      STZ-treated diabetic animals (DM) were diabetic animals perfused with 1.5 uM of
      zofenopril 4 weeks after the induction of diabetes. Our results demonstrated that
      diabetic rats are characterized by a depressed cardiac performance and that
      oxidative markers are related to alterations in cardiac function in rats with 4
      weeks of STZ-induced diabetes. Additionally, the use of zofenopril as a
      monotherapy slightly diminished cardiac damage induced by chronic hyperglycaemia.
      However, long-term follow-up intervention trials are necessary to fully
      demonstrate the benefit of zofenopril in this context. A challenge for future
      investigations will be to identify the effects of chronic administration or
      combination therapy with angiotensin-converting enzyme inhibitors in various
      models of diabetes.

PMID- 27882443
TI  - Gut Microbiota and Autism: Key Concepts and Findings.
AB  - There is an emerging body of evidence linking the intestinal microbiota with
      autism spectrum disorders (ASD). Studies have demonstrated differences in the
      composition of gut bacteria between children with ASD and controls. Certain
      intestinal bacteria have been observed in abundance and may be involved in the
      pathogenesis of ASD; including members of the Clostridium and Sutterella genus.
      Evidence from animal models suggest that certain microbial shifts in the gut may
      produce changes consistent with the clinical picture of autism, with proposed
      mechanisms including toxin production, aberrations in fermentation
      processes/products, and immunological and metabolic abnormalities. In this
      article, we review studies examining the relationship between intestinal bacteria
      and ASD, and discuss bacterial species that may be implicated and proposed
      mechanisms.

PMID- 27882444
TI  - Genomic characterization of a wild-bird-origin pigeon paramyxovirus type 1 (PPMV
      1) first isolated in the northwest region of China.
AB  - Pigeon paramyxovirus type-1(PPMV-1) is an enzootic in pigeon flocks and causes
      severe economic losses in the poultry industry in many countries. A PPMV-1
      isolate, abbreviated as PPMV-1/QL-01/CH/15, was isolated from a great spotted
      woodpecker in the northwest region of China in 2015. The complete genome was
      sequenced, and the results showed that the virus genome was 15,192 nt in length,
      in the gene arrangement 3'-NP-P-M-F-HN-L-5'. Several amino acid mutations were
      identified in the functional domains of the F and HN proteins. The pathogenicity
      index of the isolate was evaluated, and the mean death time (MDT) was 72 h and
      the intracerebral pathogenicity index (ICPI) was 0.925, indicating that this
      isolate was mesogenic. Sequencing results showed that it had a virulent Newcastle
      disease virus cleavage motif 112R-R-Q-K-R-F117 at the fusion protein cleavage
      site. Morbidity and mortality were 70% and 50%, after inoculation of pigeons,
      whereas this virus was nonpathogenic in chickens. Different immune responses of
      pigeons and chickens were induced in vivo, which led to different HI serum
      antibody titers. The results of phylogenetic and evolutionary distance analysis
      showed that this PPMV-1 strain belonged to sub-genotype VIa in class II. To our
      knowledge, this is the first identification and analysis of PPMV-1 co-circulation
      among wild birds and domestic pigeon flocks in China. The data from this study
      highlight the important role of wild birds in the dissemination of PPMV-1 and
      provide useful references for improving our understanding of the distribution and
      evolution of PPMV-1 in China.

PMID- 27882446
TI  - Impact of the size and number of swollen joints on serum C-reactive protein level
      and erythrocyte sedimentation rate in rheumatoid arthritis: a cross-sectional
      study in Japan.
AB  - No studies have yet reported the influence of swelling in individual joints on
      serum C-reactive protein and erythrocyte sedimentation rate. To examine this
      association, we used data from the NinJa registry, the largest registry of
      rheumatoid arthritis patients in Japan. Sixty-six palpable joints were
      categorized by size into three groups (small, medium-sized, and knees) with
      surface area cutoffs of 10 and 100 cm2. Of 10,720 cases registered in NinJa in
      2012, 8444 cases with either no swollen joints or swelling limited to one joint
      size category were analyzed. Groups with larger numbers of swollen joints showed
      higher levels of both markers in each joint-size category. Groups with larger
      swollen joints had higher levels of both markers compared with groups with the
      same number of (smaller) swollen joints. Linear regression revealed that the
      increments of C-reactive protein (mg/dL/joint) and erythrocyte sedimentation rate
      (mm/1 h/joint) were 0.056 and 0.89, 0.24 and 5.0, and 0.46 and 8.9 for small and
      medium-sized joints and knee joints, respectively. The levels of systemic
      inflammation markers increased with the involvement of larger and/or more joints.
      These results were successfully illustrated by the use of large-scale data, which
      eliminated wide intragroup scattering of the marker values.

PMID- 27882445
TI  - Enhanced dietary formulation to mitigate winter thermal stress in gilthead sea
      bream (Sparus aurata): a 2D-DIGE plasma proteome study.
AB  - Low water temperatures during winter are common in farming of gilthead sea bream
      in the Mediterranean. This causes metabolic disorders that in extreme cases can
      lead to a syndrome called "winter disease." An improved immunostimulatory
      nutritional status might mitigate the effects of this thermal metabolic stress. A
      trial was set up to assess the effects of two different diets on gilthead sea
      bream physiology and nutritional state through plasma proteome and metabolites.
      Four groups of 25 adult gilthead sea bream were reared during winter months,
      being fed either with a control diet (CTRL) or with a diet called "winter feed"
      (WF). Proteome results show a slightly higher number of proteins upregulated in
      plasma of fish fed the WF. These proteins are mostly involved in the immune
      system and cell protection mechanisms. Lipid metabolism was also affected, as
      shown both by plasma proteome and by the cholesterol plasma levels. Overall, the
      winter feed diet tested seems to have positive effects in terms of fish condition
      and nutritional status, reducing the metabolic effects of thermal stress.

PMID- 27882447
TI  - Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly
      Impaired Spatial Cognition at Juvenile-Age.
AB  - Inhalation anesthetics facilitate surgical procedures in millions of children
      each year. However, animal studies demonstrate that exposure to the inhalation
      anesthetic isoflurane may cause neuronal cell death in developing brains. The
      long-term cytotoxic effects of sevoflurane, the most popular pediatric
      anesthetic, have not been compared with isoflurane. Thus, this study was designed
      to compare the effects of equipotent doses of these two anesthetics on neonatal
      long-term neurotoxicity. Postnatal 7-day-old (P7) C57/BL male mice were exposed
      to 1.5% isoflurane or 2.2% sevoflurane 2 h a day for 3 days. Non-anesthetized
      mice served as controls. The effects of anesthesia on learning and memory were
      assessed using the Morris Water Maze (MWM) at Postnatal days 30 (P30) and P60
      respectively. The hippocampal content of N-methyl-D-aspartate receptor subunits
      (NMDA), brain-derived neurotrophic factor (BDNF), and synaptophysin (Syn) were
      determined by Western Blot. Neuron structure and apoptosis were assessed via
      Nissl and TUNEL staining, respectively. The isoflurane group exhibited cognitive
      impairment at P30. Repeated inhalation of isoflurane or sevoflurane caused
      different degrees of apoptosis and damaged hippocampal neurons in neonatal mice,
      particularly isoflurane. In neonatal mice, repeated exposure to isoflurane, but
      not sevoflurane, caused spatial cognitive impairments in juvenile mice. Our
      findings suggest that isoflurane induces significantly greater neurodegeneration
      than an equipotent minimum alveolar concentration of sevoflurane.

PMID- 27882449
TI  - Diametrical relationship between gray and white matter volumes in autism spectrum
      disorder and schizophrenia.
AB  - Autism spectrum disorders and schizophrenia have been variously characterized as
      separate nosological entities with overlapping deficits in social cognition or
      diametrical extremes of a phenotypic continuum. This study aimed to determine how
      these models apply to comparative morphometric data. MRI scans of the brain were
      obtained in 49 subjects with schizophrenia, 20 subjects with autism and 39
      healthy controls. Images were parcellated into 40 Brodmann areas and entered into
      repeated-measures ANOVA for between-group comparison of global and localized gray
      and white matter volumes. A pattern of lower gray mater volumes and greater white
      matter volumes was found in subjects with schizophrenia in comparison to subjects
      with autism. For both gray and white matter, this pattern was most pronounced in
      regions associated with motor-premotor and anterior frontal cortex, anterior
      cingulate, fusiform, superior and middle temporal gyri. Patient groups tended to
      diverge from healthy controls in opposite directions, with greater-than-normal
      gray matter volumes and lower-than-normal white matter volumes in subjects with
      autism and reversed patterns in subjects with schizophrenia. White matter
      reductions in subjects with autism were seen in posterior frontal lobe and along
      the cingulate arch. Normal hemispheric asymmetry in the temporal lobe was effaced
      in subjects with autism and schizophrenia, especially in the latter. Nearly
      identical distribution of changes and diametrically divergent volumetry suggest
      that autism and schizophrenia may occupy opposite extremes of the same cognitive
      continuum.

PMID- 27882450
TI  - In Memoriam: Dr. Beverly Evans-Britt.

PMID- 27882451
TI  - Competency by design: when opportunity stops knocking.

PMID- 27882452
TI  - Are we at risk of losing the soul of medicine?

PMID- 27882454
TI  - Portraying the Effect of Calcium-Binding Proteins on Cytosolic Calcium
      Concentration Distribution Fractionally in Nerve Cells.
AB  - Nerve cells like neurons and astrocytes in central nervous system (CNS) take part
      in the signaling process which means the transformation of the information from
      one cell to another via signals. The signaling process is affected by various
      external parameters like buffers calcium-binding proteins, voltage-gated calcium
      channel. In the present paper, the role of buffers in the cytoplasmic calcium
      concentration distribution is shown. The elicitation in calcium concentration is
      due to the presence of lower amount calcium-binding proteins which can be shown
      graphically. The mathematical model is designed by keeping in mind the
      physiological condition taking place in CNS of mammalian brain. The thing to be
      noted here is that the more elicitation in the calcium concentration distribution
      results in the cell death which finally give neurodegenerative disease to the
      mammalian brain. The present paper gives a glimpse of Parkinson's diseases in
      particular. Computational results are performed in Wolfram Mathematica 9.0 and
      simulated on core(TM) i5-3210M CPU @ 2.50 GHz processing speed and 4 GB memory.
      It is found that the different types of buffer like ethylene glycol-bis([Formula:
      see text]-aminoethyl ether)-N,N,N',N'-tetraacetic acid, 1,2-bis(o
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and calmodulin have noteworthy
      effect at different fractions of time.

PMID- 27882448
TI  - Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.
AB  - Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity
      depends on NAD+ levels and thus on the cellular metabolic status. SIRTs regulate
      energy metabolism and mitochondrial function. They orchestrate the stress
      response and damage repair. Through these functions sirtuins modulate the course
      of aging and affect neurodegenerative diseases. SIRTSs interact with multiple
      signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases
      (PARPs) another class of NAD+-dependent post-translational protein modifiers. The
      cross-talk between SIRTs TFs and PARPs is a highly promising research target in a
      number of brain pathologies. This review describes updated results on sirtuins in
      brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of
      mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus
      and in cytosol, respectively. The involvement of SIRTs in regulation of insulin
      like growth factor signaling in the brain during aging and in Alzheimer's disease
      was also focused. Moreover, we analyze the mechanism(s) and potential
      significance of interactions between SIRTs and several TFs in the regulation of
      cell survival and death. A critical view is given on the application of SIRT
      activators/modulators in therapy of neurodegenerative diseases.

PMID- 27882453
TI  - [Implementation of a proactive integrated primary care program for frail older
      people: from science to evidence-based practice].
AB  - BACKGROUND: Multimorbidity, functional impairment and frailty among community
      dwelling older people are causing increasing complexity in primary care. A
      proactive integrated primary care approach is therefore essential. Between
      October 2014-2015, an evidence-based proactive care program for frail older
      people was implemented in the region Noord-West Veluwe en Zeewolde, the
      Netherlands. This study evaluated the feasibility of the implementation, having a
      strong focus on the collaboration between the medical and social domain. METHODS:
      Using a mixed-methods design we evaluated several process indicators. Data were
      obtained from electronic routine medical record data within primary care,
      questionnaires, and interviews with older adults. The questionnaires provided
      information regarding the expectations and experiences towards the program and
      were sent to health care professionals at baseline and six months follow-up.
      Stakeholders from various domains were asked to fill in the questionnaire at
      baseline and twelve months follow-up. Interviews were conducted to explore the
      experiences of older adults with the program. Regional work groups were set up in
      each municipality to enhance the interdisciplinary and domain transcending
      collaboration. RESULTS: The proactive primary care program was implemented in 42
      general practices who provided care to 7904 older adults aged 75 years or older.
      A total of 101 health care professionals and 44 stakeholders filled in the
      questionnaires. The need for better structure and interdisciplinary cooperation
      seemed widespread among the participants. The implementation resulted in a
      positive significant change in the demand for a better regional healthcare
      framework (34% p <= .001) among health care professionals, and the needs for
      transparency regarding the possibilities for referral improved (27% , p = .009).
      Half of the participants reported that the regional collaboration has been
      improved after the implementation. Health care professionals and stakeholders
      gained increased attention and awareness of frail elderly in their area compared
      to before the implementation. Older people and their caregivers were positive
      about the proactive approach. The nurses reported that the screenings
      questionnaire was too lengthy and therefore time consuming. CONCLUSIONS: The
      implementation of the proactive primary care approach in daily practice was
      feasible. A strong interdisciplinary collaboration was realized. The program was
      easily adapted to the local context.

PMID- 27882455
TI  - Memory consolidation effects on memory stabilization and item integration in
      older adults.
AB  - This study examined the differential effects of aging on consolidation processes
      that strengthen newly acquired memory traces in veridical form (memory
      stabilization) versus consolidation processes that are responsible for
      integrating these memory traces into an existing body of knowledge (item
      integration). Older adults learned 13 nonwords and were tested on their memory
      for the nonwords, and on whether these nonwords impacted upon processing of
      similar-sounding English words immediately and 24 hours later. Participants
      accurately recognized the nonwords immediately, but showed significant decreases
      in delayed recognition and recall. In comparison, the nonwords impacted upon
      processing of similar-sounding words only in the delayed test. Together, these
      findings suggest that memory consolidation processes may be more evident in item
      integration than memory stabilization processes for new declarative memories in
      older adults.

PMID- 27882456
TI  - Action potential influences spatial perception: Evidence for genuine top-down
      effects on perception.
AB  - The action-specific account of spatial perception asserts that a perceiver's
      ability to perform an action, such as hitting a softball or walking up a hill,
      impacts the visual perception of the target object. Although much evidence is
      consistent with this claim, the evidence has been challenged as to whether
      perception is truly impacted, as opposed to the responses themselves. These
      challenges have recently been organized as six pitfalls that provide a framework
      with which to evaluate the empirical evidence. Four case studies of action
      specific effects are offered as evidence that meets the framework's high bar, and
      thus that demonstrates genuine perceptual effects. That action influences spatial
      perception is evidence that perceptual and action-related processes are
      intricately and bidirectionally linked.

PMID- 27882459
TI  - Analysis of Proliferation of Melanoma Cells and Mesenchymal Stem Cells in Co
      Culture and Contribution of Experimental Conditions into Interpretation of the
      Results.
AB  - A series of experiments on co-culturing of Mel IL melanoma cells and mesenhymal
      stem cells showed that these cells do not influence proliferation of each other,
      but we observed weaker adhesion of stromal stem cells to plastic in cocultures
      where with melanoma cells were grown on mesenhymal stem cells feeder. Cell
      proliferation was also considerably influenced by experimental conditions, which
      should be taken into account for correct interpretation of obtained results. The
      principles of experiments on co-culturing of cancer and stromal cells are
      formulated that take into account the most important factors influencing cell
      behavior and minimize the probability of artifact results. It was concluded that
      co-culturing conditions cells significantly affect the experimental results and
      can be the source of conflicting conclusions on mutual influence of stromal and
      cancer cells in vitro.

PMID- 27882458
TI  - Personal Identity Development in Hispanic Immigrant Adolescents: Links with
      Positive Psychosocial Functioning, Depressive Symptoms, and Externalizing
      Problems.
AB  - The present study was designed to examine trajectories of personal identity
      coherence and confusion among Hispanic recent-immigrant adolescents, as well as
      the effects of these trajectories on psychosocial and risk-taking outcomes.
      Personal identity is extremely important in anchoring young immigrants during a
      time of acute cultural change. A sample of 302 recently immigrated (5 years or
      less in the United States at baseline) Hispanic adolescents (Mage = 14.51 years
      at baseline; SD = 0.88 years, range 14-17) from Miami and Los Angeles (47 %
      girls) completed measures of personal identity coherence and confusion at the
      first five waves of a six-wave longitudinal study; and reported on positive
      psychosocial functioning, depressive symptoms, and externalizing problems at
      baseline and at Time 6. Results indicated that identity coherence increased
      linearly across time, but that there were no significant changes in confusion
      over time and no individual differences in confusion trajectories. Higher
      baseline levels of, and improvements in, coherence predicted higher levels of
      self-esteem, optimism, and prosocial behavior at the final study timepoint.
      Higher baseline levels of confusion predicted lower self-esteem, greater
      depressive symptoms, more aggressive behavior, and more rule breaking at the
      final study timepoint. These results are discussed in terms of the importance of
      personal identity for Hispanic immigrant adolescents, and in terms of
      implications for intervention.

PMID- 27882460
TI  - Development of a Specific Substrate-Inhibitor Panel (Liver-on-a-Chip) for
      Evaluation of Cytochrome P450 Activity.
AB  - We developed a cytochrome P450 substrate-inhibitor panel for preclinical in vitro
      evaluation of drugs in a 3D histotypical microfluidic cell model of human liver
      (liver-on-a-chip technology). The concentrations of substrates and inhibitors
      were optimized to ensure reliable detection of the principal metabolites by HPLC
      mass-spectroscopy. The selected specific substrate-inhibitor pairs, namely
      bupropion/2-phenyl-2-(1-piperidinyl)propane) for evaluation of CYP2B6B activity,
      tolbutamide/sulfaphenazole for CYP2C9, omeprazole/(+)-N-benzylnirvanol for
      CYP2C19, and testosterone/ketoconazole for CYP3A4, enable reliable evaluation of
      the drug metabolism pathway. In contrast to animal models characterized by
      species-specific expression profile and activity of cytochrome P450 isoforms, our
      in vitro model reflects the metabolism of human hepatocytes in vivo.

PMID- 27882461
TI  - Migration and Proliferative Activity of Mesenchymal Stem Cells in 3D Polylactide
      Scaffolds Depends on Cell Seeding Technique and Collagen Modification.
AB  - We analyzed viability of mesenchymal stem cells seeded by static and dynamic
      methods to highly porous fibrous 3D poly-L-lactide scaffolds with similar
      physical and chemical properties, but different spatial organization modified
      with collagen. Standard collagen coating promoted protein adsorption on the
      scaffold surface and improved adhesive properties of 100 MU-thick scaffolds.
      Modification of 600-MU scaffolds with collagen under pressure increased
      proliferative activity of mesenchymal stem cells seeded under static and dynamic
      (delivery of 100,000 cells in 10 ml medium in a perfusion system at a rate of 1
      ml/min) conditions by 47 and 648%, respectively (measured after 120-h culturing
      by MTT test). Dynamic conditions provide more uniform distribution of collagen on
      scaffold fibers and promote cell penetration into 3D poly-L-lactide scaffolds
      with thickness >600 MU.

PMID- 27882457
TI  - Cytomegalovirus Vaccines: Current Status and Future Prospects.
AB  - Congenital human cytomegalovirus (HCMV) infection can result in severe and
      permanent neurological injury in newborns, and vaccine development is accordingly
      a major public health priority. HCMV can also cause disease in solid organ
      transplant (SOT) and hematopoietic stem-cell transplant (HSCT) recipients, and a
      vaccine would be valuable in prevention of viremia and end-organ disease in these
      populations. Currently there is no licensed HCMV vaccine, but progress toward
      this goal has been made in recent clinical trials. A recombinant HCMV
      glycoprotein B (gB) vaccine has been shown to have some efficacy in prevention of
      infection in young women and adolescents, and has provided benefit to HCMV
      seronegative SOT recipients. Similarly, DNA vaccines based on gB and the
      immunodominant T-cell target, pp65 (ppUL83), have been shown to reduce viremia in
      HSCT patients. This review provides an overview of HCMV vaccine candidates in
      various stages of development, as well as an update on the current status of
      ongoing clinical trials. Protective correlates of vaccine-induced immunity may be
      different for pregnant woman and transplant patients. As more knowledge emerges
      about correlates of protection, the ultimate licensure of HCMV vaccines may
      reflect the uniqueness of the target populations being immunized.

PMID- 27882462
TI  - Proliferative Potential of Cardiomyocytes in Hypertrophic Cardiomyopathy:
      Correlation with Myocardial Remodeling.
AB  - Proliferating Ki-67+ cardiomyocytes were detected in the interventricular septum
      myocardium of adult patients with hypertrophic cardiomyopathy. In the same
      patients, the severity of hypertrophy and the degree of cardiomyocyte
      differentiation were assessed by the content of myofibrils, ultrastructural
      morphology, and the pattern of connexin 43-containing gap junction distribution.
      Adult Ki-67+ cardiomyocytes containing sarcomeric alpha-actin (sarc alpha-act+)
      in the sarcoplasm (diameter 23.9+/-6.9 MU) were detected in the myocardium of
      patients with hypertrophic cardiomyopathy; their relative content varied from 2
      to 3084 cells per 1 million cardiomyocytes. Small early differentiating Ki
      67+/sarc alpha-act+ cardiomyocytes with a thin cytoplasm layer (diameter 5.9+/
      1.7 MU) constituted from 3 to 2262 cells per 1 million cardiomyocytes. These
      cells were found in the myocardium with the most pronounced structural changes:
      hypertrophy of cardiomyocytes with signs of their partial dedifferentiation.

PMID- 27882463
TI  - The Use of Technetium-99m for Intravital Tracing of Transplanted Multipotent
      Stromal Cells.
AB  - We studied the possibility of in vivo tracing of multipotent mesenchymal stromal
      cells labeled with a radiophermaceutic preparation based on metastable isotope
      Technetium-99m and injected to rats with modeled traumatic brain injury.
      Accumulation of labeled cells occurred primarily in the liver and lungs. The
      cells distribution in internal organs greatly varied depending on the
      administration route. Cell injection into the carotid artery led to their
      significant accumulation in the damaged brain hemisphere, while intravenous
      injection was followed by diffuse cell distribution in all brain structures.
      Scintigraphy data were confirmed by magnetic resonance imaging and histological
      staining of cells. Visualization of stem cells labeled with Technetium-99m-based
      preparation by scintigraphy is an objective and highly informative method
      allowing real-time in vivo cell tracing in the body.

PMID- 27882464
TI  - Analysis of Reparative Activity of Platelet Lysate: Effect on Cell Monolayer
      Recovery In Vitro and Skin Wound Healing In Vivo.
AB  - Platelet lysate prepared from donor platelet concentrate and pooled according to
      a developed technique stimulates migration of multipotent mesenchymal stromal
      cells of the human adipose tissue and promotes healing of the monolayer defect in
      cultures of human fibroblasts and multipotent mesenchymal stromal cells in vitro
      in concentrations close those of fetal calf serum (5-10%). Lysate of platelets
      from platelet-rich rat blood plasma stimulated healing of the skin defect by
      promoting epithelialization and granulation tissue formation. The regenerative
      properties of platelet lysate in vivo increased with increasing its
      concentration.

PMID- 27882465
TI  - Colonization by Staphylococcus aureus of Nano-Structured Fluorinated Surfaces,
      Formed by Different Methods of Ion-Plasma Technology.
AB  - Colonization of fluorinated surfaces produced by ion-plasma technology by
      Staphylococcus aureus was studied by scanning electron microscopy and surface
      energy analysis. It was shown that the intensity of colonization was determined
      by the surface relief and fluorine content. Formation of nanostructured surfaces
      accompanied by a sharp decrease in the surface energy prevented adhesion of
      Staphylococcus aureus cells to the fluorine-containing surface.

PMID- 27882466
TI  - Frequency of 3' VNTR Polymorphism in the Dopamine Transporter Gene SLC6A3 in
      Humans Predisposed to Antisocial Behavior.
AB  - Predisposition to antisocial behavior can be related to the presence of certain
      polymorphic variants of genes encoding dopaminergic system proteins. We studied
      the frequencies of allele variants and genotypes of variable number tandem repeat
      polymorphism in 3' untranslated region (3' VTNR) of the dopaminergic transporter
      SLC6A3 gene in Caucasian men committed socially dangerous violent and non-violent
      crimes. Alleles with 9 and 10 repeats were most frequent in both the control
      group and group of men predisposed to antisocial behavior. At the same time, the
      10/10 genotype was more frequently observed in the group of men prone to
      antisocial non-violent behavior. Hence, the presence of certain variants of 3'
      VTNR polymorphism of SLC6A3 gene in men is associated with predisposition to
      certain forms of antisocial behavior.

PMID- 27882467
TI  - Are there keystone mycorrhizal fungi associated to tropical epiphytic orchids?
AB  - In epiphytic orchids, distinctive groups of fungi are involved in the symbiotic
      association. However, little is known about the factors that determine the
      mycorrhizal community structure. Here, we analyzed the orchid mycorrhizal fungi
      communities associated with three sympatric Cymbidieae epiphytic tropical orchids
      (Cyrtochilum flexuosum, Cyrtochilum myanthum, and Maxillaria calantha) at two
      sites located within the mountain rainforest of southern Ecuador. To characterize
      these communities at each orchid population, the ITS2 region was analyzed by
      Illumina MiSeq technology. Fifty-five mycorrhizal fungi operational taxonomic
      units (OTUs) putatively attributed to members of Serendipitaceae,
      Ceratobasidiaceae and Tulasnellaceae were identified. Significant differences in
      mycorrhizal communities were detected between the three sympatric orchid species
      as well as among sites/populations. Interestingly, some mycorrhizal OTUs
      overlapped among orchid populations. Our results suggested that populations of
      studied epiphytic orchids have site-adjusted mycorrhizal communities structured
      around keystone fungal species. Interaction with multiple mycorrhizal fungi could
      favor orchid site occurrence and co-existence among several orchid species.

PMID- 27882468
TI  - Discrete element modelling of sediment falling in water.
AB  - The Discrete Element Method (DEM) is a discrete, particle-based method commonly
      used in studies involving granular media, e.g. sediment transport, and
      geomechanics. It is heavily dependent on particle properties, and one important
      component is the force model, which relates the relative positions and velocities
      of the simulated particles to the forces they experience. In this paper we model
      a collection of lightly compacted granular material, released at a short distance
      above a flat base in a quiescent fluid --similar to the process whereby sediment
      tailings are released back into the sea during nodule harvesting. We employ
      different typical force models, and consider how their varying components affect
      the simulated outcome. The results are compared with a physical experiment of
      similar dimensions. We find that a realistic simulation is achieved when the
      force model considers the local solid fraction in the drag force, and
      incorporates the hydrodynamic effect of neighbouring particles. The added mass
      effect increases the accuracy of the outcome, but does not contribute
      significantly in a qualitative sense.

PMID- 27882469
TI  - Influence of the SSO/ASTRO Margin Reexcision Guidelines on Costs Associated with
      Breast-Conserving Surgery.
AB  - BACKGROUND: The reported reexcision rates vary significantly for patients with
      invasive breast cancer undergoing breast-conserving surgery (BCS). This
      variability is a function of both the positive pathologic margin rate and the
      interpretation of an adequate pathologic margin. The influence of the SSO/ASTRO
      margin guidelines on reexcision rates and the potential cost savings is of
      interest from both quality and health economics perspectives. METHODS: A
      retrospective analysis of all patients undergoing BCS during a 3-year period
      (January 1, 2010-December 31, 2012) was performed. The reexcision rate and the
      pathologic margin status were assessed to determine the number of patients with
      pathologic negative margins who underwent reexcision. A decision analysis using
      previously published case costing information was used to determine the potential
      savings associated with avoidance of reoperation for patients meeting guidelines
      criteria. RESULTS: The analysis included 512 patients who underwent attempted BCS
      for invasive breast cancer. Reoperations occurred for 25% (126/512) of the BCS
      cohort, but this rate could potentially be decreased to 16% (44/512) if these
      guidelines were applied. Based on our cost model, application of the guidelines
      would provide a potential cost savings of $698 (95% confidence interval $523
      $893) per patient undergoing attempted BCS in our population. CONCLUSIONS:
      Adherence to the SSO-ASTRO guidelines could prevent one-third of reoperations
      among patients undergoing BCS. This would result in significant cost savings to
      the health care system while avoiding unnecessary operations. Use of guidelines
      has the potential to improve the quality of care provided to patients.

PMID- 27882470
TI  - Comparison of Detrusor Muscle Sampling Rate in Monopolar and Bipolar
      Transurethral Resection of Bladder Tumor: A Randomized Trial.
AB  - PURPOSE: Our aim was to investigate the detrusor muscle sampling rate after
      monopolar versus bipolar transurethral resection of bladder tumor (TURBT).
      METHODS: This was a single-center, prospective, randomized, phase III trial on
      monopolar versus bipolar TURBT. Baseline patient characteristics, disease
      characteristics and perioperative outcomes were compared, with the primary
      outcome being the detrusor muscle sampling rate in the TURBT specimen.
      Multivariate logistic regression analyses on detrusor muscle sampling were
      performed. RESULTS: From May 2012 to December 2015, a total of 160 patients with
      similar baseline characteristics were randomized to receive monopolar or bipolar
      TURBT. Fewer patients in the bipolar TURBT group required postoperative
      irrigation than patients in the monopolar TURBT group (18.7 vs. 43%; p = 0.001).
      In the whole cohort, no significant difference in the detrusor muscle sampling
      rates was observed between the bipolar and monopolar TURBT groups (77.3 vs.
      63.3%; p = 0.057). In patients with urothelial carcinoma, bipolar TURBT achieved
      a higher detrusor muscle sampling rate than monopolar TURBT (84.6 vs. 67.7%; p =
      0.025). On multivariate analyses, bipolar TURBT (odds ratio [OR] 2.23, 95%
      confidence interval [CI] 1.03-4.81; p = 0.042) and larger tumor size (OR 1.04,
      95% CI 1.01-1.08; p = 0.022) were significantly associated with detrusor muscle
      sampling in the whole cohort. In addition, bipolar TURBT (OR 2.88, 95% CI 1.10
      7.53; p = 0.031), larger tumor size (OR 1.05, 95% CI 1.01-1.10; p = 0.035), and
      female sex (OR 3.25, 95% CI 1.10-9.59; p = 0.033) were significantly associated
      with detrusor muscle sampling in patients with urothelial carcinoma. CONCLUSIONS:
      There was a trend towards a superior detrusor muscle sampling rate after bipolar
      TURBT. Further studies are needed to determine its implications on disease
      recurrence and progression.

PMID- 27882472
TI  - The Role of Venous and Arterial Resection in Pancreatic Cancer Surgery.
AB  - Pancreatic cancer continues to carry a dismal prognosis with the majority of
      patients presenting at advanced stages of disease. Complete surgical resection
      remains essential for prolonging survival and increasing the possibility of cure.
      However, few patients will be resectable at diagnosis, with a significant portion
      presenting with borderline or locally advanced disease. The addition of vascular
      resection and reconstruction at the time of pancreatectomy enables expansion of
      the patient population able to undergo resection with curative intent and achieve
      tumor-free margins. This review provides an overview of the literature regarding
      the role of venous and arterial resection in the treatment of pancreatic cancer,
      with a focus on outcomes including survival, morbidity, and mortality.

PMID- 27882471
TI  - Fra-1 Regulates the Expression of HMGA1, Which is Associated with a Poor
      Prognosis in Human Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: The expression of Fos-related antigen 1 (Fra-1) affects tumor
      progression, migration, and invasion. In this study, we identified the genes
      regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC). METHODS: We
      constructed Fra-1 knockdown models via the transfection of small interfering RNA
      (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in
      the knockdown models were analyzed using a microarray and a Biobase Upstream
      Analysis, while the expression levels of the candidate genes in the primary
      tumors of surgical specimens obtained from ESCC patients were determined using
      real-time polymerase chain reaction (PCR) and immunohistochemical staining. The
      clinicopathological features were then analyzed. RESULTS: The Biobase Upstream
      Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant
      gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1
      was revealed in subsequent chromatin immunoprecipitation PCR experiments.
      Patients with a positive HMGA1 expression had a poor prognosis, and a
      multivariate analysis demonstrated a positive HMGA1 expression to be a
      significant independent prognostic factor. CONCLUSION: HMGA1 is regulated by Fra
      1 in ESCC, and the HMGA1 expression is significantly associated with a poor
      prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a
      practical treatment strategy against ESCC in the future.

PMID- 27882474
TI  - Effects of CCK-8 and Cystathionine gamma-Lyase/Hydrogen Sulfide System on Acute
      Lung Injury in Rats.
AB  - Acute lung injury (ALI) is mainly characterized by diffusive injuries to lung
      epithelium and increased permeability of alveolar-capillary membranes caused by
      various factors, which leads to pulmonary edema and pulmonary closure.
      Lipopolysaccharide (LPS), which is the main component of the cell wall of gram
      negative bacteria, is one of the most important factors causing pulmonary
      infection and ALI. More and more reports have indicated that hydrogen sulfide
      (H2S) is closely correlated with ALI and has anti-inflammation function, while
      the specific mechanism needs further investigation. Cholecystokinin-octapeptide
      (CCK-8), which is an important endogenous functional fragment belonging to CCK
      family, participates in anti-inflammatory and anti-endotoxic shock (ES). Whether
      CCK-8 plays important roles in curing ALI also needs further investigation.
      Herein, we concluded that CCK-8 alleviated the ALI induced by LPS via regulating
      the catalytic activity of cystathionine gamma-lyase (CSE) and the formation of
      H2S. This work provides new medicine-designed target for clinical doctor to
      prevent and cure ALI.

PMID- 27882476
TI  - A German Sexological Perspective on Male Chronophilias.

PMID- 27882473
TI  - Foxp3, Regulatory T Cell, and Autoimmune Diseases.
AB  - Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance
      to autologous components and maintains immune system homeostasis. The abnormal
      function of Tregs is relevant to the pathogenesis of systemic lupus erythematosus
      (SLE), rheumatoid arthritis (RA), and other autoimmune diseases. Therefore,
      therapeutic modulation of Tregs could be a potent means of treating autoimmune
      diseases. Human Tregs are diverse, however, and not all of them have
      immunosuppressive effects. Forkhead box P3 (Foxp3), a pivotal transcription
      factor of Tregs that is crucial in maintaining Treg immunosuppressive function,
      can be expressed heterogeneously or unstably across Treg subpopulations. Insights
      into modulating Treg differentiation on the level of DNA transcription or protein
      modification may improve the success of Treg modifying immunotherapies. In this
      review, we will summarize three main prospects: the regulatory mechanism of
      Foxp3, the influence on Foxp3 and Tregs in autoimmune diseases, then finally, how
      Tregs can be used to treat autoimmune diseases.

PMID- 27882477
TI  - Sexual Fantasy and Masturbation Among Asexual Individuals: An In-Depth
      Exploration.
AB  - Human asexuality is generally defined as a lack of sexual attraction. We used
      online questionnaires to investigate reasons for masturbation, and explored and
      compared the contents of sexual fantasies of asexual individuals (identified
      using the Asexual Identification Scale) with those of sexual individuals. A total
      of 351 asexual participants (292 women, 59 men) and 388 sexual participants (221
      women, 167 men) participated. Asexual women were significantly less likely to
      masturbate than sexual women, sexual men, and asexual men. Asexual women were
      less likely to report masturbating for sexual pleasure or fun than their sexual
      counterparts, and asexual men were less likely to report masturbating for sexual
      pleasure than sexual men. Both asexual women and men were significantly more
      likely than sexual women and men to report that they had never had a sexual
      fantasy. Of those who have had a sexual fantasy, asexual women and men were
      significantly more likely to endorse the response "my fantasies do not involve
      other people" compared to sexual participants, and consistently scored each
      sexual fantasy on a questionnaire as being less sexually exciting than did sexual
      participants. When using an open-ended format, asexual participants were more
      likely to report having fantasies about sexual activities that did not involve
      themselves, and were less likely to fantasize about topics such as group sex,
      public sex, and having an affair. Interestingly, there was a large amount of
      overlap between sexual fantasies of asexual and sexual participants. Notably,
      both asexual and sexual participants (both men and women) were equally likely to
      fantasize about topics such as fetishes and BDSM.

PMID- 27882475
TI  - The Spatio-Temporal Expression Profiles of CD4 + T Cell Differentiation and
      Function-Related Genes During EAE Pathogenesis.
AB  - Multiple sclerosis is a CD4+ T cell-mediated autoimmune disease of the central
      nervous system. The unbalance of the cytokines and transcription factors critical
      for CD4+ T cell differentiation and function is probably the main reason that
      causes MS. We detected the mRNA expression changes of key cytokines and
      transcription factors which are critical for Th1, Th2, Th17, and Treg cell
      differentiation and function in different tissues during EAE pathogenesis. We
      fund that each gene not only has its own featured expression changes, but also
      has interaction with one another, which composes a network of immunity.
      Understanding the roles of key cytokines and transcription factors in these
      processes will help to understand disease pathogenesis and supply indications for
      disease therapy.

PMID- 27882479
TI  - Albendazole Microcrystal Formulations Based on Chitosan and Cellulose
      Derivatives: Physicochemical Characterization and In Vitro Parasiticidal Activity
      in Trichinella spiralis Adult Worms.
AB  - The oral route has notable advantages to administering dosage forms. One of the
      most important questions to solve is the poor solubility of most drugs which
      produces low bioavailability and delivery problems, a major challenge for the
      pharmaceutical industry. Albendazole is a benzimidazole carbamate extensively
      used in oral chemotherapy against intestinal parasites, due to its extended
      spectrum activity and low cost. Nevertheless, the main disadvantage is the poor
      bioavailability due to its very low solubility in water. The main objective of
      this study was to prepare microcrystal formulations by the bottom-up technology
      to increase albendazole dissolution rate, in order to enhance its antiparasitic
      activity. Thus, 20 novel microstructures based on chitosan, cellulose
      derivatives, and poloxamer as a surfactant were produced and characterized by
      their physicochemical properties and in vitro biological activity. To determine
      the significance of type and concentration of polymer, and presence or absence of
      surfactant in the crystals, the variables area under the curve, albendazole
      microcrystal solubility, and drug released (%) at 30 min were analyzed with a
      three-way ANOVA. This analysis indicated that the microcrystals made with
      hydroxyethylcellulose or chitosan appear to be the best options to optimize oral
      absorption of the active pharmaceutical ingredient. The in vitro evaluation of
      anthelmintic activity on adult forms of Trichinella spiralis identified system
      S10A as the most effective, of choice for testing therapeutic efficacy in vivo.

PMID- 27882478
TI  - Unexpected hosts: imaging parasitic diseases.
AB  - Radiologists seldom encounter parasitic diseases in their daily practice in most
      of Europe, although the incidence of these diseases is increasing due to
      migration and tourism from/to endemic areas. Moreover, some parasitic diseases
      are still endemic in certain European regions, and immunocompromised individuals
      also pose a higher risk of developing these conditions. This article reviews and
      summarises the imaging findings of some of the most important and frequent human
      parasitic diseases, including information about the parasite's life cycle,
      pathophysiology, clinical findings, diagnosis, and treatment. We include malaria,
      amoebiasis, toxoplasmosis, trypanosomiasis, leishmaniasis, echinococcosis,
      cysticercosis, clonorchiasis, schistosomiasis, fascioliasis, ascariasis,
      anisakiasis, dracunculiasis, and strongyloidiasis. The aim of this review is to
      help radiologists when dealing with these diseases or in cases where they are
      suspected. Teaching Points * Incidence of parasitic diseases is increasing due to
      migratory movements and travelling. * Some parasitic diseases are still endemic
      in certain regions in Europe. * Parasitic diseases can have complex life cycles
      often involving different hosts. * Prompt diagnosis and treatment is essential
      for patient management in parasitic diseases. * Radiologists should be able to
      recognise and suspect the most relevant parasitic diseases.

PMID- 27882481
TI  - Assessment criteria for vitamin D deficiency/insufficiency in Japan: proposal by
      an expert panel supported by the Research Program of Intractable Diseases,
      Ministry of Health, Labour and Welfare, Japan, the Japanese Society for Bone and
      Mineral Research and the Japan Endocrine Society [Opinion].
AB  - Vitamin D is indispensable for the maintenance of bone and mineral health.
      Inadequate vitamin D action increases the risk for various
      musculoskeletal/mineral events including fracture, fall, secondary
      hyperparathyroidism, diminished response to antiresorptives,
      rickets/osteomalacia, and hypocalcemia. Its most common cause in recent years is
      vitamin D deficiency/insufficiency, clinically defined by a low serum 25
      hydroxyvitamin D [25(OH)D] level. Guidelines for vitamin D
      insufficiency/deficiency defined by serum 25(OH)D concentrations have been
      published all over the world. In Japan, however, the information on the
      associations between serum 25(OH)D and bone and mineral disorders has not been
      widely shared among healthcare providers, partly because its measurement had not
      been reimbursed with national medical insurance policy until August 2016. We have
      set out to collect and analyze Japanese data on the relationship between serum
      25(OH)D concentration and bone and mineral events. Integrating these domestic
      data and published guidelines worldwide, here, we present the following
      assessment criteria for vitamin D sufficiency/insufficiency/deficiency using
      serum 25(OH)D level in Japan. (1) Serum 25(OH)D level equal to or above 30 ng/ml
      is considered to be vitamin D sufficient. (2) Serum 25(OH)D level less than 30
      ng/ml but not less than 20 ng/ml is considered to be vitamin D insufficient. (3)
      Serum 25(OH)D level less than 20 ng/ml is considered to be vitamin D deficient.
      We believe that these criteria will be clinically helpful in the assessment of
      serum 25(OH)D concentrations and further expect that they will form a basis for
      the future development of guidelines for the management of vitamin D
      deficiency/insufficiency.

PMID- 27882480
TI  - Phenotype, biochemical features, genotype and treatment outcome of pyridoxine
      dependent epilepsy.
AB  - We report treatment outcome of eleven patients with pyridoxine-dependent epilepsy
      caused by pathogenic variants in ALDH7A1 (PDE-ALDH7A1). We developed a clinical
      severity score to compare phenotype with biochemical features, genotype and
      delays in the initiation of pyridoxine. Clinical severity score included 1)
      global developmental delay/ intellectual disability; 2) age of seizure onset
      prior to pyridoxine; 3) current seizures on treatment. Phenotype scored 1-3 =
      mild; 4-6 = moderate; and 7-9 = severe. Five patients had mild, four patients had
      moderate, and two patients had severe phenotype. Phenotype ranged from mild to
      severe in eight patients (no lysine-restricted diet in the infantile period) with
      more than 10-fold elevated urine or plasma alpha-AASA levels. Phenotype ranged
      from mild to moderate in patients with homozygous truncating variants and from
      moderate to severe in patients with homozygous missense variants. There was no
      correlation between severity of the phenotype and the degree of alpha-AASA
      elevation in urine or genotype. All patients were on pyridoxine, nine patients
      were on arginine and five patients were on the lysine-restricted diet. 73% of the
      patients became seizure free on pyridoxine. 25% of the patients had a mild
      phenotype on pyridoxine monotherapy. Whereas, 100% of the patients, on the lysine
      restricted diet initiated within their first 7 months of life, had a mild
      phenotype. Early initiation of lysine-restricted diet and/or arginine therapy
      likely improved neurodevelopmental outcome in young patients with PDE-ALDH7A1.

PMID- 27882482
TI  - Immobilization and Stabilization of Beta-Xylosidases from Penicillium
      janczewskii.
AB  - beta-Xylosidases are critical for complete degradation of xylan, the second main
      constituent of plant cell walls. A minor beta-xylosidase (BXYL II) from
      Penicillium janczewskii was purified by ammonium sulfate precipitation (30%
      saturation) followed by DEAE-Sephadex chromatography in pH 6.5 and elution with
      KCl. The enzyme presented molecular weight (MW) of 301 kDa estimated by size
      exclusion chromatography. Optimal activity was observed in pH 3.0 and 70-75 
      degrees C, with higher stability in pH 3.0-4.5 and half-lives of 11, 5, and 2 min
      at 65, 70, and 75  degrees C, respectively. Inhibition was moderate with Pb+2 and
      citrate and total with Cu+2, Hg+2, and Co+2. Partially purified BXYL II and BXYL
      I (the main beta-xylosidase from this fungus) were individually immobilized and
      stabilized in glyoxyl agarose gels. At 65  degrees C, immobilized BXYL I and BXYL
      II presented half-lives of 4.9 and 23.1 h, respectively, therefore being 12.3
      fold and 33-fold more stable than their unipuntual CNBr derivatives (reference
      mimicking soluble enzyme behaviors). During long-term incubation in pH 5.0 at 50 
      degrees C, BXYL I and BXYL II glyoxyl derivatives preserved 85 and 35% activity
      after 25 and 7 days, respectively. Immobilized BXYL I retained 70% activity after
      10 reuse cycles of p-nitrophenyl-beta-D-xylopyranoside hydrolysis.

PMID- 27882483
TI  - Effect of CO2 Concentration on Growth and Biochemical Composition of Newly
      Isolated Indigenous Microalga Scenedesmus bajacalifornicus BBKLP-07.
AB  - Photosynthetic mitigation of CO2 through microalgae is gaining great importance
      due to its higher photosynthetic ability compared to plants, and the biomass can
      be commercially exploited for various applications. CO2 fixation capability of
      the newly isolated freshwater microalgae Scenedesmus bajacalifornicus BBKLP-07
      was investigated using a 1-l photobioreactor. The cultivation was carried at
      varying concentration of CO2 ranging from 5 to 25%, and the temperature and light
      intensities were kept constant. A maximum CO2 fixation rate was observed at 15%
      CO2 concentration. Characteristic growth parameters such as biomass productivity,
      specific growth rate, and maximum biomass yield, and biochemical parameters such
      as carbohydrate, protein, lipid, chlorophyll, and carotenoid were determined and
      discussed. It was observed that the effect of CO2 concentration on growth and
      biochemical composition was quite significant. The maximum biomass productivity
      was 0.061 +/- 0.0007 g/l/day, and the rate of CO2 fixation was 0.12 +/- 0.002
      g/l/day at 15% CO2 concentration. The carbohydrate and lipid content were maximum
      at 25% CO2 with 26.19 and 25.81% dry cell weight whereas protein, chlorophyll,
      and carotenoid contents were 32.89% dry cell weight, 25.07 MUg/ml and 6.15 MUg/ml
      respectively at 15% CO2 concentration.

PMID- 27882484
TI  - Diagnostic challenge of Diamond-Blackfan anemia in mothers and children by whole
      exome sequencing.
AB  - Diamond-Blackfan anemia (DBA) is a pure red cell aplasia that arises from
      defective ribosomal proteins (RPs). Patients with this rare ribosomopathy present
      with neonatal anemia and occasional dysmorphism. Clinical heterogeneity and
      clusters of causative RP genes hamper the diagnosis and perinatal management. We
      report three mother-and-child pairs of anemia who were finally diagnosed by whole
      exome sequencing. Each pair showed distinct disease severity and response to
      anemia treatment. Only one mother had the diagnostic dysmorphism, including short
      stature, webbed neck, and thenar hypoplasia. This mother had a frame-shift
      mutation of RPL11 (exon 3, c.58_59del). Her infant showed transient neonatal
      anemia, but had no mutations of RP genes. The other mother-child pairs had a
      missense mutation of RPS19 (exon 4, c.185G>A), and a splicing error of RPS7 (exon
      3, c.76-1G>T), respectively. Other than the reported mutations, there were no
      variants in genes significantly associated with anemia. Our results suggested
      that whole-exome sequencing (WES) is effective for achieving a prompt and correct
      diagnosis of human ribosomopathy.

PMID- 27882485
TI  - Pharmacodynamics of T cell function for monitoring pharmacologic
      immunosuppression after allogeneic hematopoietic stem cell transplantation.
AB  - Information on pharmacodynamic monitoring after allogeneic hematopoietic cell
      transplantation (allo-SCT) to evaluate individual responses to immunosuppressive
      drugs is scarce. We studied the relationship between a panel of pharmacodynamic
      markers monitored during the first 3 months after transplant and the occurrence
      of graft-versus-host disease (GVHD). Lymphocyte activation assessed by
      intracellular ATP concentration in CD4+ T cells, a high percentage of CD8+
      effector T cells, and a low percentage of CD4+ regulatory T (Treg) cells
      correlated significantly with GVHD. A cutoff value of 0.5 for the CD8+ effector
      T/Treg ratio provided the most accurate diagnosis of GVHD (sensitivity 58.8%,
      specificity 91%). These pharmacodynamic markers may provide an efficient
      complement to standard pharmacokinetic monitoring of immunosuppressive drugs
      after allo-SCT.

PMID- 27882486
TI  - VEP analysis methods in children with optic nerve hypoplasia: relationship to
      visual acuity and optic disc diameter.
AB  - PURPOSE: Assessing vision in young children with optic nerve hypoplasia (ONH) is
      challenging due to multi-directional infantile nystagmus, the range of optic
      nerve loss, and cognitive delay. This study examined visual evoked potential
      (VEP) responses and averaging techniques in children with ONH. The assumption is
      that EEG epochs with inconsistent temporal phase would be associated with
      nystagmus, signal reduction due to axon loss, and visual inattention. METHODS: A
      retrospective chart review was performed on 44 children (average age 2.2 years;
      SD 1.9). Optic disc diameter was estimated by ophthalmoscopy. Visual function was
      measured under binocular viewing and then compared to the eye with the larger
      optic disc to exclude secondary amblyopia. Visual acuity was measured by Teller
      cards or by recognition optotypes, and both measures were converted into log
      minimum angle of resolution (logMAR). VEPs were recorded to onset/offset of
      horizontal gratings and to reversing checkerboards. Signal-to-noise ratios (SNRs)
      were estimated from phase consistency across epochs in the Fourier domain. VEPs
      were also averaged after (1) correction of epochs for phase shifts across a
      limited bandwidth, or (2) selection of only epochs showing phase consistency.
      RESULTS: Optic disc diameter, logMAR, VEP amplitudes, and VEP SNR were all
      significantly inter-correlated. Optic disc diameter correlated best with VEP SNR
      (Spearman rho = 0.82; p < 0.001). Age-corrected logMAR correlated with optic disc
      diameter and VEP SNR (Spearman rho = -0.695 and 0.70, respectively; p < 0.001).
      VEP latency poorly correlated with optic disc diameter or logMAR. Correction of
      phase shifts or selection of epochs based on phase consistency significantly
      increased VEP amplitude and SNR for children with optic disc diameters <1000
      microns. Correction of phase inconsistency did not improve the correlation of VEP
      parameters with optic disc diameter or with logMAR. CONCLUSIONS: In ONH, the size
      of the optic nerve is correlated with VEP SNR and logMAR. The results imply a
      direct relationship between the reduction in optic nerve axons and generalized
      reduction in visual function. Our calculation of VEP SNR provides objective
      assessment of optic nerve function that is independent of subjective scoring of
      VEP peaks.

PMID- 27882487
TI  - Delivery of Small Interfering RNA to Inhibit Vascular Endothelial Growth Factor
      in Zebrafish Using Natural Brain Endothelia Cell-Secreted Exosome Nanovesicles
      for the Treatment of Brain Cancer.
AB  - Although small interfering RNA (siRNA) holds great therapeutic promise, its
      delivery to the disease site remains a paramount obstacle. In this study, we
      tested whether brain endothelial cell-derived exosomes could deliver siRNA across
      the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from
      brain endothelial bEND.3 cell culture media and vascular endothelial growth
      factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection
      reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry
      staining studies indicated that wild-type exosomes significantly increased the
      uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells,
      decreased fluorescence intensity was observed in the cells treated with the
      tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0.05). In
      the transport study, exosomes also enhanced the permeability of rhodamine 123 in
      a co-cultured monolayer of brain endothelial bEND.3 cell and astrocyte.
      Inhibition at the expression of VEGF RNA and protein levels was observed in
      glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs.
      Imaging results showed that exosome delivered more siRNAs across the BBB in
      Tg(fli1:GFP) zebrafish. In a xenotransplanted brain tumor model, exosome
      delivered VEGF siRNAs decreased the fluorescence intensity of labeled cancer
      cells in the brain of zebrafish. Brain endothelial cell-derived exosomes could be
      potentially used as a natural carrier for the brain delivery of exogenous siRNA.

PMID- 27882488
TI  - Quantification of motion of the thoracic aorta after ascending aortic repair of
      type-A dissection.
AB  - PURPOSE: To quantify cardiac and respiratory deformations of the thoracic aorta
      after ascending aortic graft repair. METHODS: Eight patients were scanned with
      cardiac-resolved computed tomography angiography during inspiratory/expiratory
      breath-holds. Aortic centerlines and lumen were extracted to compute the
      arclength, curvature, angulation, and cross-section shape. RESULTS: From systole
      to diastole, the angle of graft [Formula: see text] arch increased by
      2.4[Formula: see text] +/- 1.8[Formula: see text] (P < 0.01) and the angle of
      arch [Formula: see text] descending aorta decreased by 2.4[Formula: see text] +/-
      2.6[Formula: see text] (P < 0.05), while the effective diameter of the proximal
      arch decreased by 2.4 +/- 1.9% (P < 0.01), a greater change than those of the
      graft or distal arch (P < 0.05). From inspiration to expiration, the angle of
      graft [Formula: see text] arch increased by 2.8[Formula: see text] +/-
      2.6[Formula: see text] (P < 0.02) with the peak curvature increase (P < 0.05).
      Shorter graft length was correlated with greater cardiac-induced graft [Formula:
      see text] arch angulation, and longer graft length was correlated with greater
      respiratory-induced arch [Formula: see text] descending aorta angulation (R
      [Formula: see text] 0.50). CONCLUSION: The thoracic aorta changed curvature and
      angulation with cardiac and respiratory influences, driven by aortic root and
      arch motion. The thoracic aortic geometry and deformation are correlated with the
      ascending aortic graft length.

PMID- 27882490
TI  - Defining the Field of Behavioral Medicine: A Collaborative Endeavor.
AB  - PURPOSE: To respond to comments on our proposal for an update of the definition
      and scope of behavioral medicine. METHODS: We identify common themes in the
      comments and provide a response. RESULTS: We discuss the relationship of
      behavioral medicine to other disciplines and fields, the scope of behavioral
      medicine, and issues related to the application of behavioral medicine.
      CONCLUSION: Based on the comments of our esteemed colleagues and our reflection
      on those comments, we now offer the following refined definition and scope of
      behavioral medicine. 'Behavioral medicine can be defined as the field
      characterized by the collaboration among multiple disciplines concerned with the
      development and integration of biomedical and behavioral knowledge relevant to
      health and disease, and the application of this knowledge to prevention, health
      promotion, diagnosis, treatment, rehabilitation, and care. The scope of
      behavioral medicine extends from bio-behavioral mechanisms (i.e. the interaction
      among biomedical, psychological, social, societal, cultural and environmental
      processes related to health and disease), to clinical diagnosis and intervention,
      and to public health'. We propose to use this refined definition and scope as the
      starting point for seeking further input from the ISBM member societies.

PMID- 27882489
TI  - Psychological Distress Mediates the Effect of Alexithymia on 2-Year Change in HIV
      Viral Load.
AB  - PURPOSE: Individuals with trait alexithymia (AL) display poor cognitive
      assimilation of thoughts, feelings, and emotions. This may result in the
      persistence of stress, anxiety, and depressive disorders. The cumulative effect
      of this psychological distress is also linked clinical markers of human
      immunodeficiency virus (HIV) disease progression. This study examines the
      indirect effect of AL on HIV viral load as a function of baseline levels and
      change in psychological distress. METHODS: N = 123 HIV positive adults aged 37.9
      +/- 9.2 years provided blood samples for HIV-1 viral RNA and CD4 T lymphocytes
      along with self-reported stress, anxiety, and depression every 6 months for 2
      years. A second-order conditional latent growth model was used to represent
      baseline and 2-year change in cumulative levels of psychological distress and to
      test the indirect effect of baseline levels of trait AL on change in HIV-1 viral
      load through this latent measure. RESULTS: AL was associated with baseline and
      latent change in psychological distress. Furthermore, baseline psychological
      distress predicted 2-year change in HIV-1 viral RNA after controlling for viral
      load at baseline. Altogether, trait AL had a significant indirect effect on
      change in viral load (beta = 0.16, p = 0.03) as a function of baseline levels of
      distress. CONCLUSION: Identification and communication of thoughts, feelings, and
      emotions are important for long-term psychological adaptation in HIV. Greater
      psychological distress, in turn, allows for persistence of peripheral viral
      replication.

PMID- 27882491
TI  - Influence of phosphorous fertilization on copper phytoextraction and antioxidant
      defenses in castor bean (Ricinus communis L.).
AB  - Application of fertilizers to supply appropriate nutrients has become an
      essential agricultural strategy for enhancing the efficiency of phytoremediation
      in heavy metal contaminated soils. The present study was conducted to investigate
      the beneficial effects of three types of phosphate fertilizers (i.e., oxalic acid
      activated phosphate rock (APR), Ca(H2PO4)2, and NaH2PO4) in the range of 0-600 mg
      P kg-1 soil, on castor bean growth, antioxidants [antioxidative enzymes and
      glutathione (GSH)], and Cu uptake. Results showed that with the addition of
      phosphorus fertilizers, the dry weight of castor bean and the Cu concentration in
      roots increased significantly, resulting in increased Cu extraction. The
      phosphorus concentration in both shoots and roots was increased as compared with
      the control, and the Ca(H2PO4)2 treatment had the greatest effect. Application of
      APR, NaH2PO4, and Ca(H2PO4)2 reduced the malondialdehyde (MDA) content, and the
      activity of the two antioxidant enzymes superoxide dismustase (SOD, EC 1.15.1.1)
      and catalase (CAT, EC 1.11.1.6) in the leaves of castor bean. GSH concentration
      in leaves increased with the increasing levels of phosphorus applied to soil as
      well as the accumulation of phosphorus in shoots, compared to the control. These
      results demonstrated that the addition of phosphorus fertilizers can enhance the
      resistance of castor bean to Cu and increase the Cu extraction efficiency of the
      plant from contaminated soils.

PMID- 27882492
TI  - Distribution of As, Cd, and Pb in seafood in Southern China and their oral
      bioavailability in mice.
AB  - The distribution of the toxic elements As, Cd, and Pb in nine different types of
      seafood from Shenzhen, China, was investigated by using inductively coupled
      plasma mass spectrometry (ICP-MS). The results revealed that the concentrations
      of arsenic (As) in fish (Lutjanus erythropterus, Paralichthys olivaceus) and in
      bivalve (Meretrix meretrix) and cadmium (Cd) in scallop (Argopecten irradians)
      exceed the limits established by food safety regulations in China and EU
      (European Union). Furthermore, the bioavailability of As, Cd, and lead (Pb) in
      mice after 20-day oral ingestion of Crassostrea rivularis was investigated, and
      the total rate of absorption of toxic elements in samples from the liver and
      kidney tissues and blood was determined. The results of this in vivo trial
      indicated that the oral bioavailability of As, Cd, and Pb was approximately 0.33,
      0.45, and 0.74%, respectively.

PMID- 27882493
TI  - Environmental status of groundwater affected by chromite ore processing residue
      (COPR) dumpsites during pre-monsoon and monsoon seasons.
AB  - Chromite ore processing residue (COPR) is generated by the roasting of chromite
      ores for the extraction of chromium. Leaching of carcinogenic hexavalent chromium
      (Cr(VI)) from COPR dumpsites and contamination of groundwater is a key
      environmental risk. The objective of the study was to evaluate Cr(VI)
      contamination in groundwater in the vicinity of three COPR disposal sites in
      Uttar Pradesh, India, in the pre-monsoon and monsoon seasons. Groundwater samples
      (n = 57 pre-monsoon, n = 70 monsoon) were taken in 2014 and analyzed for Cr(VI)
      and relevant hydrochemical parameters. The site-specific ranges of Cr(VI)
      concentrations in groundwater were <0.005 to 34.8 mg L-1 (Rania), <0.005 to 115
      mg L-1 (Chhiwali), and <0.005 to 2.0 mg L-1 (Godhrauli). Maximum levels of Cr(VI)
      were found close to the COPR dumpsites and significantly exceeded safe drinking
      water limits (0.05 mg L-1). No significant dependence of Cr(VI) concentration on
      monsoons was observed.

PMID- 27882495
TI  - Occurrence, profiles, and ecological risks of polybrominated diphenyl ethers in
      mangrove sediments of Shantou, China.
AB  - Surface sediments were collected from three mangrove wetlands (Yifeng Xi,
      Shuanghan, and Su'ai Wan) in Shantou coastal zone of South China to investigate
      spatial distributions of polybrominated diphenyl ethers (PBDEs). The results
      demonstrate that PBDEs were detected in all the samples, indicating their
      widespread occurrence in coastal sediments of the studied area. Sigma9PBDEs
      (defined as the sum of nine targeted PBDE congeners except BDE-209) and BDE-209
      are in the range of 2.3 to 11.5 and 16.7 to 58.2 ng/g, respectively. BDE-209 is
      the dominant PBDE congener in all sediment samples. The sediment concentrations
      of ?9PBDEs and BDE-209 among the three wetlands decrease in the order of Su'ai
      Wan > Shuanghan > Yifeng Xi. The concentrations of ?9PBDEs are higher in mangrove
      sediments than in mudflats, but no obvious regularity can be found on the
      correlation between mangrove species and PBDE levels in sediments. The contents
      of total organic carbon are moderately correlated with BDE-209 concentrations in
      sediments but not with ?9PBDE concentrations. The samples collected from
      different locations show slightly different composition profiles except BDE-209,
      with BDE-100 and BDE-47 being the pre-dominated congeners. The mudflats exhibit
      higher abundances of tri- to hexa-substituted congeners than the mangrove
      sediments. Ecological risk assessment demonstrates that the surface sediments
      from Shantou may pose a potential ecological risk of exposure to sediment
      dwelling organisms.

PMID- 27882494
TI  - Role of Rhizophagus irregularis in alleviating cadmium toxicity via improving the
      growth, micro- and macroelements uptake in Phragmites australis.
AB  - Arbuscular mycorrhizal (AM) fungi have been used to alleviate heavy metal stress
      on plant growth and uptake of micro- and macroelements. A greenhouse pot
      experiment was conducted to verify the effects of AM fungus Rhizophagus
      irregularis on the growth, physiological characteristics, total Cd, and element
      uptake of Phragmites australis under different Cd stress (in the range of 0-20 mg
      L-1). The results showed that the symbiosis could effectively alleviate Cd
      toxicity with greater root biomass, higher photosynthesis rate, and lower levels
      of malonaldehyde (MDA) and proline than non-mycorrhizal plants could. However,
      reduced transpiration rate (Tr) and stomatal conductance (g s) indicated R.
      irregularis protected host plants from Cd stress (>=5 mg L-1) via the stomatal
      closure. Although micro- and macroelements displayed differently in the presence
      of Cd, higher concentrations were still detected in mycorrhizal plants in
      contrast to non-mycorrhizal plants. Moreover, step multiple regression
      significantly demonstrated Pnmax, stem diameter (Sd), and g s were the important
      factors with regard to total Cd uptake in the symbiosis, but Mn affected to non
      mycorrhizal plants. These results suggested R. irregularis could alleviate the
      competition between Mn and Cd by altering plant physiology. This work clearly
      demonstrated that R. irregularis can be able to support P. australis growth
      better even though under high Cd stress (>1 mg L-1), suggesting its good
      potential for practical use in high Cd-contaminated areas.

PMID- 27882496
TI  - Biomarkers in Tubifex tubifex for the metalaxyl and metalaxyl-M toxicity
      assessment in artificial sediment.
AB  - Efficacy and potential environmental risks should be considered when applying
      enantiopure pesticides. In this study, Tubifex tubifex and its oxidative stress
      biomarkers were assessed for the toxicity of metalaxyl and metalaxyl-M in
      sediment. The toxicity assessment was conducted with artificial sediment and
      reconstituted water. Five test concentrations (from 0 to 100 mg/kg) were set for
      the short-term (4 days) exposure. The long-term (28 days) exposure was conducted
      with the environmental concentration (from 0.5 to 5 mg/kg). For the short-term
      exposure, the increase of superoxide dismutase (SOD) activity was observed, and a
      clear concentration-response relationship was found in the metalaxyl treatments.
      The decrease of catalase (CAT) and glutathione peroxidase (GPx) activity could be
      caused by oxidative stress. The decrease of glutathione (GSH) content and the
      increase of glutathione-S-transferase (GST) might be due to antioxidation defense
      and detoxification mechanisms. The increase of malondialdehyde (MDA) might be due
      to the saturation of antioxidant systems and the accumulation and toxicity of
      contaminations. In the long-term exposure, the changes of biomarkers in T.
      tubifex reflected the oxidative stress and detoxification metabolisms. GSH and
      the related enzymes were important in detoxification processes and involved in
      the oxidative stress in toxicity mechanism. The long-term direct contact bioassay
      is sensitive and appropriate to reflect the lower concentration of contaminants.

PMID- 27882499
TI  - MD simulation of high-resolution X-ray structures reveals post-translational
      modification dependent conformational changes in HSF-DNA interaction.

PMID- 27882498
TI  - Parent Training Programs for Ethnic Minorities: a Meta-analysis of Adaptations
      and Effect.
AB  - This meta-analysis focuses on parent training programs for ethnic minority
      families and reports on (i) the adaptation of program content and (ii) the
      process that informs these adaptations. Relevant studies are reviewed to
      determine the adaptations made and the impact of the adaptations on parenting and
      child outcomes. Studies were eligible for inclusion if they enrolled
      predominantly ethnic minority parents with children aged 0-12 years, used a
      randomized controlled trial design with post-intervention assessments, focused on
      group-based parent training programs and on prevention of parenting problems, and
      reported parenting behavior outcomes. A total of 18 studies were included in the
      analysis. The results show that parent training programs targeting ethnic
      minority parents have a small but significant effect on improving parenting
      behavior (k = 18, Cohen's d = 0.30), child outcomes (k = 16, Cohen's d = 0.13),
      and parental perspectives (k = 8, Cohen's d = 0.19). Most of the programs made
      adaptations related to surface and deep structure sensitivity. Programs with
      cultural adaptations, especially deep structure sensitivity (k = 7, Cohen's d =
      0.54), are more effective in improving parenting behavior. Because only a third
      of the included studies provided details on the processes that guided the
      adaptations made, additional studies are needed to provide information on the
      process of adaptation; this will enable others to learn from the procedures that
      can be undertaken to culturally adapt interventions.

PMID- 27882497
TI  - Soluble TLR2 and 4 concentrations in cerebrospinal fluid in HIV/SIV-related
      neuropathological conditions.
AB  - HIV in the central nervous system (CNS) mainly infects microglial cells which are
      known to express toll-like receptors (TLRs). This paper aimed to study the role
      of soluble TLR2 (sTLR2), sTLR4, and other inflammatory markers in cerebrospinal
      fluid (CSF) in HIV/Simian immunodeficiency virus (SIV)-related neurological
      sequelae. We determined sTLR2 and sTLR4 levels in CSF and serum/plasma of SIV
      infected rhesus macaques with and without neurological sequelae, as well as in
      HIV-infected patients with and without cognitive impairments and Alzheimer's
      disease (AD) patients and matched controls. CSF cytokines and chemokines levels
      were analyzed in macaques as markers of neuroinflammation, while neopterin and
      S100B CSF concentrations were measured in HIV-infected patients as microglial and
      astrocyte marker, respectively. We found detectable levels of sTLR2 and sTLR4 in
      CSF of macaques and humans. Furthermore, CSF sTLR2 and sTLR4 concentrations were
      higher in SIV-infected macaques with neurological sequelae compared to those
      without neurological complications (p = 0.0003 and p = 0.0006, respectively). CSF
      IL-8 and monocyte chemoattractant protein-1 (MCP-1) levels were elevated in
      macaques with neurological sequelae, and a positive correlation was found between
      CSF levels of sTLR2/4 and IL-8 and MCP-1. Also in humans, elevated CSF sTLR4
      levels were found in HIV-infected patients with cognitive impairments compared to
      HIV-infected patients with normal cognition (p = 0.019). Unlike CSF S100B levels,
      neopterin correlated positively with sTLR2 and sTLR4. No difference was found in
      plasma and CSF sTLR2 and sTLR4 levels between AD patients and control subjects (p
      = 0.26). In conclusion, CSF sTLR2 and sTLR4 may play a role in HIV/SIV-related
      neuroinflammation and subsequent neuropathology.

PMID- 27882501
TI  - A review of a GP registrar-run mobile health clinic for homeless people.
AB  - BACKGROUND: Homeless people have excessively high morbidity and mortality rates,
      yet they face barriers accessing primary care. A mobile health clinic, staffed by
      GP registrars, was developed to provide services to homeless people, particularly
      rough sleepers and sex workers. AIM: The aims were to improve access to primary
      care and to challenge the stereotypes and prejudices of GP registrars through
      direct contact with homeless people. DESIGN AND SETTING: This was a qualitative
      study; questionnaires were completed on the mobile health clinic and two focus
      groups were conducted. METHODS: All service users were asked to complete a
      questionnaire over a 3 month period. Two focus groups were conducted with 6 and
      14 GP registrars who had worked on the bus. RESULTS: There was an 80% response
      rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no
      way to access the free primary care to which they are entitled. Had the clinic
      not been available, over half would not have sought further treatment and 16%
      would have gone to an Emergency Department. Ninety-one percent of users rated the
      service 10/10. The focus groups found that GP registrars who worked on the mobile
      health clinic had decreased negative stereotypes, increased empathy, and more
      knowledge of homeless issues. Furthermore, they intended to ensure that homeless
      people will not face discrimination in their future practice. CONCLUSION: A GP
      Registrar-run Mobile Health Clinic achieved its aims of improving access to
      primary care for rough sleepers and sex workers, and challenging stereotypes of
      GP Registrars.

PMID- 27882502
TI  - Institutional Responsibility and the Flawed Genomic Biomarkers at Duke
      University: A Missed Opportunity for Transparency and Accountability.
AB  - When there have been substantial failures by institutional leadership in their
      oversight responsibility to protect research integrity, the public should demand
      that these be recognized and addressed by the institution itself, or the funding
      bodies. This commentary discusses a case of research failures in developing
      genomic predictors for cancer risk assessment and treatment at a leading
      university. In its review of this case, the Office of Research Integrity, an
      agency within the US Department of Health and Human Services, focused their
      report entirely on one individual faculty member and made no comment on the
      institution's responsibility and its failure to provide adequate oversight and
      investigation. These actions missed an important opportunity to emphasize the
      institution's critical responsibilities in oversight of research integrity and
      the importance of institutional transparency and accountability.

PMID- 27882500
TI  - Heart rate acceleration runs and deceleration runs in patients with obstructive
      sleep apnea syndrome.
AB  - PURPOSE: This study aimed to explore the patterns of heart rate acceleration runs
      and deceleration runs in patients with obstructive sleep apnea syndrome and to
      investigate the influence of apnea events on this pattern. METHODS: The 6-h
      electrocardiography results of patients who were referred for overnight
      polysomnography were retrospectively analyzed. The frequencies of heart rate
      acceleration runs and deceleration runs of different lengths were calculated for
      each patient and compared among patients with obstructive sleep apnea syndrome of
      varying degrees of severity, between patients with obstructive sleep apnea on and
      off continuous positive airway pressure, and between two matched groups of
      patients with idiopathic central sleep apnea and obstructive sleep apnea.
      RESULTS: A total of 231 patients were enrolled. Patients with severe obstructive
      sleep apnea exhibited significantly increased frequencies of long acceleration
      and deceleration runs after multivariate adjustment, while no significant
      differences were observed in the frequencies of short runs. Thirty-nine
      obstructive sleep apnea patients who were treated with continuous positive airway
      pressure showed a significant decrease in the frequency of long deceleration runs
      and a decreasing trend in the frequency of long acceleration runs. Patients with
      idiopathic pure central sleep apnea exhibited no significant changes in the
      frequencies of acceleration and deceleration runs after they were placed on
      continuous positive airway pressure. CONCLUSIONS: The distributions of heart rate
      acceleration and deceleration runs are related to the severity of obstructive
      sleep apnea. Long runs are more closely related to obstructive respiratory
      events, while short runs do not appear to be related to these events.

PMID- 27882503
TI  - Proving that China has a Profession of Engineering: A Case Study in
      Operationalizing a Concept Across a Cultural Divide.
AB  - This article assumes that a profession is a number of individuals in the same
      occupation voluntarily organized to earn a living by openly serving a moral ideal
      in a morally-permissible way (a discipline) beyond what law, market, morality,
      and public opinion would otherwise require. Our question is whether the concept
      of profession (so defined) may have a far wider range than the term, so that, for
      example, pointing out that a certain language lacks a word for "profession" in
      our sense, is not enough to show that those who speak the language also lack the
      concept. We believe the survey of 71 Chinese reported here begins to answer that
      question. This article has four parts. The first describes who was interviewed,
      how, when, and so on. The second describes some important features of the
      survey's questions, explaining how the questions track the concept of profession.
      The third part reports and interprets the results relevant to our question. The
      forth defends a tentative answer to the question with which we began-arguing the
      survey supports the claim that China has a profession of engineering. This
      article should serve as a "proof of concept", that is, a model for similar
      studies around the world both of engineering and of other occupations thought to
      be professions.

PMID- 27882505
TI  - Antitumor immunity and advances in cancer immunotherapy.

PMID- 27882504
TI  - Media Portrayal of a Landmark Neuroscience Experiment on Free Will.
AB  - The concept of free will has been heavily debated in philosophy and the social
      sciences. Its alleged importance lies in its association with phenomena
      fundamental to our understandings of self, such as autonomy, freedom, self
      control, agency, and moral responsibility. Consequently, when neuroscience
      research is interpreted as challenging or even invalidating this concept, a
      number of heated social and ethical debates surface. We undertook a content
      analysis of media coverage of Libet's et al.'s (Brain 106(Pt 3):623-642, 1983)
      landmark study, which is frequently interpreted as posing a serious challenge to
      the existence of free will. Media descriptions of Libet et al.'s experiment
      provided limited details about the original study. Overall, many media articles
      reported that Libet et al.'s experiments undermined the existence of free will,
      despite acknowledging that several methodological limitations had been identified
      in the literature. A propensity to attribute greater credibility than warranted
      to neurobiological explanations could be at stake.

PMID- 27882506
TI  - Cosmetics Use-Related Adverse Events and Determinants Among Jigjiga Town
      Residents, Eastern Ethiopia.
AB  - INTRODUCTION: Non-medicated cosmetics use is very common among the Ethiopian
      population. However, little is known about these products' related adverse
      events. The aim of this study was to assess the prevalence and determinants of
      cosmetics-related adverse events among Jigjiga Town residents, Eastern Ethiopia.
      METHODS: A community-based cross-sectional study design was conducted in May and
      June 2014. Semi-structured interviews were used to collect cosmetics use pattern
      and related adverse events. For assessing determinants, logistic regression was
      used and statistical significance was set at p < 0.05. RESULTS: Overall, 600
      participants were approached with a 93% response rate. Ninety-three percent (n =
      521) of them reported the use of cosmetics at least once within 2 weeks prior to
      this study, and of these, 229 (44%) used traditional herbal cosmetics along with
      modern cosmetics. A total of 342 (61%) reported experiencing adverse events of
      which the most common reported were: allergic reactions, 149 (36%); the
      appearance of acne, 66 (16%); and hirsutism, 52 (12.5%). The occurrence of
      cosmetics-related adverse events were significantly associated with the number of
      cosmetics used per day, the frequency of use, mixing of different types of
      cosmetics together, and mixing of cosmetics with water or saliva. CONCLUSION: A
      higher proportion of cosmetic users reported experiencing at least one adverse
      event. The number of cosmetic products and frequency of use were important
      predictors for experiencing adverse events. This implies the need to consider
      safety concerns related to cosmetic use. Approaches to address such issues may
      include awareness creation programs and promoting the concept of cosmetovigilance
      among cosmetic sellers, users, and other stakeholders.

PMID- 27882508
TI  - Regional early development and eruption of permanent teeth: case report.
AB  - BACKGROUND: Early development and eruption of permanent teeth are rarely reported
      in scientific literature. Early eruption of permanent teeth has been reported to
      occur due to local factors such as trauma or dental abscesses in primary teeth,
      and in systemic conditions. Congenital diffuse infiltrating facial lipomatosis
      (CDIFL) is a rare condition that belongs to a group of lipomatosis tumours. In
      this disorder, the mature adipocytes invade adjacent soft and hard tissues in the
      facial region. Accelerated tooth eruption is one of the dental anomalies
      associated with CDIFL. CASE REPORT: A 3-year-old boy presented with a swelling of
      the lower lip localised early development and eruption of permanent teeth and
      dental caries involving many primary teeth. TREATMENT: The planned treatment
      included biopsy of the swollen lower lip to confirm the diagnosis, surgical
      reduction and reconstruction of lip aesthetics. The management of the carious
      primary teeth included preventative and comprehensive dental care and
      extractions. These procedures were completed under general anaesthesia due to the
      child's young age and poor cooperation. The lip biopsy showed features of CDIFL
      such as the presence of infiltrating adipose tissue, prominent number of nerve
      bundles and thickened vessels. FOLLOW-UP: The high recurrence rate of CDIFL
      mandates long-term monitoring during the facial growth period of the child.
      Follow-up care by the paediatric dentist and maxillofacial surgeon has been
      required to manage all aspects of this congenital malformation. CONCLUSION: This
      rare disorder has many implications affecting child's facial aesthetics,
      psychological well being, developing occlusion and risk of dental caries. A multi
      disciplinary approach is needed for management of this condition.

PMID- 27882507
TI  - Plant phenological observations in rural and industrial central Italy areas.
AB  - The physiological stress caused by particular pollution conditions can result in
      phenological phase shifts that can include a block in vegetative or reproductive
      development. The main aim of the present study was to determine and analyse the
      mean development trends of some winter deciduous species in comparison to the
      climate tendencies, as calculated within two phenological gardens in the Arezzo
      and Perugia areas of central Italy. Moreover, a phenological comparison between
      the guide species of the two phenological gardens, one located in an industrial
      area, and the other in a farming area, was carried out. The phenological
      evidences showed significant phase displacements for the common guide species
      present in both the gardens which however may be explained by the meteorological
      performances above all in the Perugia not polluted area. In these terms, there
      were no evident phenological effects on the plants from the industrial area
      pollutants in the Arezzo garden. Moreover, also the temperature reduction
      tendencies at the end of spring not influenced significantly the phenological
      behaviours of the plant species not inducing them toward a predictable delay of
      reproductive and adult leaves phases.

PMID- 27882509
TI  - What's Important to the Patient? Informational Needs of Patients Making Decisions
      About Hepatitis C Treatment.
AB  - BACKGROUND AND OBJECTIVES: Multiple treatment options with direct-acting
      antivirals are now available for hepatitis C virus (HCV). Study aims were to
      understand (1) the informational topics patients want to have to make informed
      treatment decisions; (2) the importance patients place on each topic; and (3) the
      topics patients prioritize as most important. METHODS: We used a mixed-methods
      study of two samples recruited from an academic liver center. Participants were
      not currently on treatment. Sample I (n = 45) free listed all informational
      topics deemed important to decision making. Raw responses were coded into several
      broad and subcategories. Sample II (n = 38) rated the importance of the
      subcategories from Sample I and ranked their highest priorities on two surveys,
      one containing topics for which sufficient research existed to inform patients
      ('static'), and the other containing topics that would require additional
      research. RESULTS: The topics listed by Sample I fell into six broad categories
      with 17 total subcategories. The most oft-cited informational topics were harms
      of treatment (100%), treatment benefits (62%), and treatment regimen details
      (84%). Sample II rated 16 of 17 subcategories as "pretty important' or "extremely
      important". Sample II prioritized (1) viral cure, (2) long-term survival, and (3)
      side effects on the survey of topics requiring additional research, and (1) liver
      disease, (2) lifestyle changes, and (3) medication details on the second survey
      of the most important static topics patients needed. CONCLUSIONS: Patients
      weighed several informational topics to make an informed decision about HCV
      treatment. These findings lay the groundwork for future patient-centered outcomes
      research in HCV and patient-provider communication to enhance patients' informed
      decision making regarding direct-acting antiviral treatment options.

PMID- 27882510
TI  - Planned Treatment of Advanced Metastatic Disease with Completion Ablation After
      Hepatic Resection.
AB  - PURPOSE: The aim of this study is to describe a modified treatment strategy with
      image-guided percutaneous ablation after hepatic resection as a completion method
      to surgical eradication of liver metastases ("completion ablation [CA]").
      METHODS: We conducted a retrospective analyses of patients who underwent CA
      within 180 days from the liver surgical resection to eradicate liver metastases
      present on the pre-surgical cross-sectional imaging or identified during
      intraoperative ultrasound that were not resected due to various reasons. Lesions
      treated with CA were evaluated for local tumor progression (LTP). Patients were
      evaluated for hepatic- and overall-recurrence-free survivals (hepatic-RFS and
      overall-RFS, respectively) and overall survival (OS). RESULTS: Sixteen patients
      (10 females; median age 55 years, range 28-69) underwent CA of 21 lesions (median
      size 8 mm, range 6 to 22). Indications for the use of CA were small future liver
      remnant in 10 (63%), inability to identify the lesion during surgical exploration
      in 3 (19%), and technical difficulty of resection in 3 (19%) patients. No liver
      related complications were recorded following the surgical resection or the CA
      procedures. Primary and secondary CA efficacy rates were 95 and 100%,
      respectively. LTP was 0% at a median clinical follow-up of 27 months (range 4.0
      108 months). Five-year hepatic-RFS, overall-RFS, and OS were 36, 16, and 51%,
      respectively. CONCLUSION: The use of CA as a complement to surgical resection is
      safe and effective. Such approach could potentially expand the surgical candidacy
      for patients with limited liver functional reserve and reduce postoperative
      morbidity and mortality in this selected patient population with more advanced
      disease.

PMID- 27882514
TI  - A Gay Couple Meets Their Mormon Doctor.

PMID- 27882511
TI  - Over 700 Whipples for Pancreaticobiliary Malignancies: Postoperative Morbidity Is
      an Additional Negative Prognostic Factor for Distal Bile Duct Cancer.
AB  - BACKGROUND: Distal cholangiocarcinomas and pancreatic cancers both arise from
      pancreaticobiliary epithelium. Despite their common origin, there is a possible
      discrepancy in outcome. We analysed the surgical, pathological and survival
      outcome of resected distal cholangiocarcinoma compared with pancreatic cancer.
      METHODS: All cases of resected distal cholangiocarcinoma and pancreatic cancer
      from 1998 to 2014 were extracted from our database. Outcomes were compared.
      RESULTS: There were 54 (7.6%) cases of cholangiocarcinoma and 656 (92.4%)
      pancreatic cancer. Cholangiocarcinoma showed lower T and N stage, lymphatic and
      perineural invasion (p < 0.05), worse surgical outcome (p < 0.05) and less access
      to adjuvant therapy if compared with pancreatic cancer (72.7 vs. 83.1%, p =
      0.05). Both showed a similar disease-specific survival (35 vs. 29 months, p =
      0.3). Independent predictors of prognosis for pancreatic cancer were resection
      margin, grading, perineural invasion, T and N status, whereas for
      cholangiocarcinoma were grading and occurrence of POPF. CONCLUSION: Considering a
      large cohort of resected periampullary cancers, cholangiocarcinoma is extremely
      rare. An earlier diagnosis is associated with better pathological predictors of
      outcome but increased postoperative morbidity compared to pancreatic cancer,
      particularly POPF. Consequent decrease in the access to adjuvant therapy for
      complicated cholangiocarcinoma might explain why survival is as poor as for
      pancreatic cancer.

PMID- 27882512
TI  - Linear-Stapled Side-to-Side Esophagojejunostomy with Hand-Sewn Closure of the
      Common Enterotomy After Prophylactic and Therapeutic Total Gastrectomy.
AB  - After total gastrectomy, anastomosis-related complications such as leak or
      stricture can be highly morbid. Between July 2005 and December 2015, a linear
      stapled side-to-side esophagojejunostomy with hand-sewn closure of the common
      enterotomy (modified Orringer technique) was used for Roux-en-Y reconstruction
      after prophylactic total gastrectomy in 22 germline CDH1 mutation carriers and
      after therapeutic total gastrectomy in 18 patients diagnosed with gastric
      adenocarcinoma. All operations were performed by the same surgeon. No patient in
      either cohort developed a clinically evident anastomotic leak, one patient (2.5%)
      developed a contained radiographic leak that healed without intervention, and one
      patient (2.5%) developed an anastomotic stricture treated by endoscopic
      dilatation 7 months after operation. These rates were lower than radiographic
      leak and stricture rates in a comparison group of 32 patients who received a
      completely hand-sewn esophagojejunostomy (6.3 and 3.1%, respectively). Here, we
      describe how to perform the linear-stapled esophagojejunostomy anastomosis.

PMID- 27882513
TI  - Comparison of clinico-microbiological profile and treatment outcome of in-house
      and referred post cataract surgery endophthalmitis in a tertiary care center in
      South India.
AB  - BACKGROUND: The purpose of the study is to compare the clinico-microbiological
      profile and treatment outcome of in-house vs referred cases of post cataract
      surgery endophthalmitis in a tertiary eye care facility in South India. METHODS:
      The clinical records of 50 culture-positive cases each of in-house (group A) and
      referred (group B) post cataract surgery endophthalmitis were analyzed. The
      management protocol was similar in both groups. RESULTS: The time to report to
      the institute was longer in group B (group B 13.63 [+/-11.67; 95% CI, 9.95-17.31]
      days; group A 6.83 [+/-7.61; 95% CI, 4.57-9.09] days; P = 0.002). The average
      inflammatory scores in presentation were comparable (group A 17.85 +/- 5.83;
      group B 18.18 +/- 7.35; P = 0.243). The final visual outcome was clinically
      superior in group A (>=20/200-group A 60.42% and group B 44%, P = 0.11; <=20/400
      group A 37.5% and group B 52%, P = 0.62), but statistically not significant.
      There were more gram-positive organisms in group A (62% vs 38%; P = 0.027) and
      more gram-negative organisms in group B (52% vs 24%; P = 0.007). Gram-positive
      bacteria were mostly sensitive to vancomycin (95.24% to 96.67%), but gram
      negative bacteria were partly sensitive to ceftazidime (58.33% to 64%).
      CONCLUSIONS: One could suspect gram-negative infection more often in the referred
      cases of endophthalmitis. While vancomycin could continue to be the antibiotic of
      choice in gram-positive bacteria, specific antibiotic following due sensitivity
      for gram-negative bacteria should replace the empiric use of ceftazidime.

PMID- 27882515
TI  - Collaborative Care for Anxiety: What's Inside the Black Box and How Can It Be
      Improved?

PMID- 27882517
TI  - Cost Effectiveness of Apixaban versus Warfarin or Aspirin for Stroke Prevention
      in Patients with Atrial Fibrillation: A Greek Perspective.
AB  - BACKGROUND: Strokes attributed to atrial fibrillation (AF) represent a major
      cause of adult disability and a great burden to society and healthcare systems.
      OBJECTIVES: Our objective was to assess the cost effectiveness of apixaban, a
      direct acting oral anticoagulant (DOAC), versus warfarin or aspirin for patients
      with AF in the Greek healthcare setting. METHODS: We used a previously published
      Markov model to simulate clinical events for patients with AF treated with
      apixaban, the vitamin K antagonist (VKA) warfarin, or aspirin. Clinical events
      (ischemic and hemorrhagic stroke, intracranial hemorrhage, other major bleed,
      clinically relevant non-major bleed, myocardial infarction, and cardiovascular
      [CV] hospitalizations) were modeled using efficacy data from the ARISTOTLE and
      AVERROES clinical trials. The cohort's baseline characteristics also sourced from
      these trials. Among VKA-suitable patients, 64.7% were men with a mean age of 70
      years and average CHADS2 (cardiac failure, hypertension, age, diabetes, stroke2)
      score of 2.1, whereas 58.5% of VKA-unsuitable patients were men with a mean age
      of 70 years and a CHADS2 score of 2.0. A panel of experts (cardiologists and
      internists) provided information on the resource use associated with the
      management of AF. Cost calculations reflect the local clinical setting and a
      third-party payer perspective (?, discounted at 3%). RESULTS: Based on a
      simulation of 1000 VKA-suitable patients over a lifetime horizon, the use of
      apixaban versus warfarin resulted in 26 fewer strokes and systemic embolisms in
      total, 65 fewer bleeds, 41 fewer myocardial infarctions, and 29 fewer CV-related
      deaths, with an incremental cost-effectiveness ratio (ICER) of ?14,478/quality
      adjusted life-year (QALY). For VKA-unsuitable patients, apixaban versus aspirin
      resulted in 72 fewer strokes and systemic embolisms and 57 fewer CV-related
      deaths, with an ICER of ?7104/QALY. Sensitivity analyses indicated that results
      were robust. CONCLUSIONS: Based on the present analysis, apixaban represents a
      cost-effective treatment option versus warfarin and aspirin for the prevention of
      stroke in patients with AF from a Greek healthcare payer perspective over a
      lifetime horizon.

PMID- 27882516
TI  - Risk of medication overuse headache across classes of treatments for acute
      migraine.
AB  - BACKGROUND: The most commonly prescribed medications used to treat migraine
      acutely are single analgesics, ergots, opioids, and triptans. Due to varying
      mechanisms of action across drug classes, there is reason to believe that some
      classes may be less likely than others to elicit Medication Overuse Headache
      (MOH) than others. We therefore aimed to determine whether certain classes of
      acute migraine drugs are more likely to elicit MOH than others. METHODS: A
      comprehensive systematic literature was conducted to identify studies of varying
      designs that reported on MOH within the considered treatment classes. Only
      studies that reported MOH according to the International Classification of
      Headache Disorders (ICHD) were considered. Since no causal comparative design
      studies were identified; data from prevalence studies and surveys were retrieved.
      Prevalence-based relative risks between treatment classes were calculated by
      integrating both medication overuse and medication use from published studies.
      For each pair wise comparison, pooled relative risks were calculated as the
      inverse variance weighted average. RESULTS: A total of 29 studies informed the
      relative risk between treatment classes, all of which reported country-specific
      data. Five studies reported country-specific medication use data. For triptans
      versus analgesics the study relative risks generally favored triptans. The pooled
      relative risk was 0.65 (i.e., relative risk reduction of 35 %). For ergots versus
      analgesics, a similar trend was observed in favor of ergots with a relative risk
      of 0.41. For triptans versus ergots, the direction of effect was mixed, and the
      pooled relative risk was 1.07. Both triptans and ergots appeared favorable when
      compared to opioids, with pooled relative risks of 0.35 and 0.76, respectively.
      However, the evidence was limited for these comparisons. Analgesics and opioids
      also appeared to yield similar risk of MOH (pooled relative risk 1.09).
      CONCLUSION: Our study suggests that in patients receiving acute migraine
      treatment, analgesics and opioids are associated with a higher risk of developing
      MOH compared with other treatments. These findings provide incentive for better
      monitoring of use of analgesics and opioids for treating acute migraine, and
      suggest possible clinical preference for use of so-called "migraine-specific"
      treatments, that is, triptans and ergots.

PMID- 27882518
TI  - Residents' and Fellows' Knowledge and Attitudes About Eating Disorders at an
      Academic Medical Center.
AB  - OBJECTIVE: This study examined physician residents' and fellows' knowledge of
      eating disorders and their attitudes toward patients with eating disorders.
      METHODS: Eighty physicians across disciplines completed a survey. The response
      rate for this survey across disciplines was 64.5 %. RESULTS: Participants
      demonstrated limited knowledge of eating disorders and reported minimal comfort
      levels treating patients with eating disorders. Psychiatry discipline (p =
      0.002), eating disorder experience (p = 0.010), and having >=4 eating disorder
      continuing medical education credits (p = 0.037) predicted better knowledge of
      anorexia nervosa but not bulimia nervosa. Psychiatry residents (p = 0.041), and
      those who had treated at least one eating disorder patient (p = 0.006), reported
      significantly greater comfort treating patients with eating disorders.
      CONCLUSION: These results suggest that residents and fellows from this sample may
      benefit from training to increase awareness and confidence necessary to treat
      patients with eating disorders. Sufficient knowledge and comfort are critical
      since physicians are often the first health care provider to have contact with
      patients who have undiagnosed eating disorders.

PMID- 27882519
TI  - Integration of Basic and Clinical Science in the Psychiatry Clerkship.
AB  - OBJECTIVE: Integration of basic and clinical science is a key component of
      medical education reform, yet best practices have not been identified. The
      authors compared two methods of basic and clinical science integration in the
      psychiatry clerkship. METHODS: Two interventions aimed at integrating basic and
      clinical science were implemented and compared in a dementia conference: flipped
      curriculum and coteaching by clinician and physician-scientist. The authors
      surveyed students following each intervention. Likert-scale responses were
      compared. RESULTS: Participants in both groups responded favorably to the
      integration format and would recommend integration be implemented elsewhere in
      the curriculum. Survey response rates differed significantly between the groups
      and student engagement with the flipped curriculum video was limited.
      CONCLUSIONS: Flipped curriculum and co-teaching by clinician and physician
      scientist are two methods of integrating basic and clinical science in the
      psychiatry clerkship. Student learning preferences may influence engagement with
      a particular teaching format.

PMID- 27882521
TI  - Listening: An Underlying Competency in Psychiatry Education.

PMID- 27882520
TI  - App Use in Psychiatric Education: A Medical Student Survey.
AB  - OBJECTIVE: The objective of the study is to understand and appraise app use by
      medical students during their clerkships. METHODS: Following Creighton University
      IRB approval, a voluntary and anonymous paper-based, 15-question survey was
      distributed to third-year medical students. Data were analyzed using Microsoft
      Excel. RESULTS: Of 112 medical students available, 76.7% (86) participated in the
      survey. All participants owned a smartphone or tablet with 84.9% using Apple iOS,
      followed by 12.8% using Android platform. Students reported using the fewest
      number of apps during surgery, psychiatry, and obstetrics and gynecology
      clerkships. The largest number of apps were used during the internal medicine
      rotation (70.3%). The three most popular apps were Epocrates, UpToDate, and
      UWorld. The most common uses for these apps were as references during the
      clerkship, followed by improving knowledge, and test taking. Perceived major
      benefits included accessibility (96% of student respondents) and interactivity
      (39.5%). Common apps used during the psychiatry clerkship included UpToDate
      (71%), Epocrates (51%), and Medscape (43%). Despite less frequent app use during
      their psychiatry clerkship, 90% felt there was a utility for educational apps in
      psychiatric education. CONCLUSIONS: Consistent with the previous literature on
      medical students preferring educational apps, students suggest developers focus
      on question bank-type apps, followed by clinical support-focused and self
      directed case-based learning apps for psychiatry clerkship learning. Educators
      should factor these modes of educational delivery into future educational app
      development. This survey shows a high degree of smartphone and tablet use among
      medical students, and they attest to mobile phone app utility in psychiatric
      education.

PMID- 27882522
TI  - The Early Career Psychiatrist and the Psychotherapeutic Identity.

PMID- 27882523
TI  - Simulation in Undergraduate Psychiatry: Exploring the Depth of Learner
      Engagement.
AB  - OBJECTIVES: Simulation-based methodologies are increasingly used in undergraduate
      medical education to expand students' exposure to complex clinical scenarios.
      Engagement of students in these simulation-based methodologies is a key
      determinant of their success in learning. Thus, the authors conducted a
      systematic review to (1) identify simulation methods in use within the
      undergraduate psychiatry curriculum and (2) assess learner engagement using these
      methods. METHODS: Following a PRISMA methodology, the authors searched MEDLINE,
      ERIC, and PsychINFO databases from 1977 to 2015. Studies applying simulation in
      undergraduate psychiatric education were reviewed. The depth of learner
      engagement was assessed using Kolb's four-stage learning cycle. RESULTS: Of 371
      publications identified, 63 met all the inclusion criteria: 48 used standardized
      patients and 16 used online or virtual learning case modules. Only one study used
      high fidelity mannequins. Three studies satisfied multiple stages in Kolb's
      Learning Cycle, including a single study that addressed all four domains.
      CONCLUSIONS: Despite the varied uses of simulation across other health
      disciplines, there were few novel or innovative uses of simulation in
      undergraduate psychiatric education since the last review in 2008. Expanding on
      the use of simulation to improve communication, build empathy, and decrease
      stigma in psychiatry is essential given the relevance to all facets of medical
      practice. Given the complexity of psychiatry, simulation interventions should
      extend beyond communication scenarios. Medical students need more opportunities
      to reflect and debrief on simulation experiences and integrate learning into new
      contexts. Faculty development should focus on these novel approaches to
      simulation to deeply engage learners and enhance outcomes.

PMID- 27882524
TI  - Clinical recognition of acute aortic dissections: insights from a large single
      centre cohort study.
AB  - AIMS: Acute aortic dissection (AD) requires immediate treatment, but is a
      diagnostic challenge. We studied how often AD was missed initially, which
      patients were more likely to be missed and how this influenced patient management
      and outcomes. METHODS: A retrospective cohort study including 200 consecutive
      patients with AD as the final diagnosis, admitted to a tertiary hospital between
      1998 and 2008. The first differential diagnosis was identified and patients with
      and without AD included were compared. Characteristics associated with a lower
      level of suspicion were identified using multivariable logistic regression, and
      Cox regression was used for survival analyses. Missing data were imputed.
      RESULTS: Mean age was 63 years, 39% were female and 76% had Stanford type A
      dissection. In 69% of patients, AD was included in the first differential
      diagnosis; this was less likely in women (adjusted relative risk [aRR]: 0.66, 95%
      CI: 0.44-0.99), in the absence of back pain (aRR: 0.51, 95% CI: 0.30-0.84), and
      in patients with extracardiac atherosclerosis (aRR: 0.64, 95% CI: 0.43-0.96).
      Absence of AD in the differential diagnosis was associated with the use of more
      imaging tests (1.8 vs. 2.3, p = 0.01) and increased time from admission to
      surgery (1.8 vs. 10.1 h, p < 0.01), but not with a difference in the adjusted
      long-term all-cause mortality (hazard ratio: 0.76, 95% CI: 0.46-1.27).
      CONCLUSION: Acute aortic dissection was initially not suspected in almost one
      third of patients, this was more likely in women, in the absence of back pain and
      in patients with extracardiac atherosclerosis. Although the number of imaging
      tests was higher and time to surgery longer, patient outcomes were similar in
      both groups.

PMID- 27882526
TI  - Reconciling change blindness with long-term memory for objects.
AB  - How can we reconcile remarkably precise long-term memory for thousands of images
      with failures to detect changes to similar images? We explored whether people can
      use detailed, long-term memory to improve change detection performance. Subjects
      studied a set of images of objects and then performed recognition and change
      detection tasks with those images. Recognition memory performance exceeded change
      detection performance, even when a single familiar object in the postchange
      display consistently indicated the change location. In fact, participants were no
      better when a familiar object predicted the change location than when the
      displays consisted of unfamiliar objects. When given an explicit strategy to
      search for a familiar object as a way to improve performance on the change
      detection task, they performed no better than in a 6-alternative recognition
      memory task. Subjects only benefited from the presence of familiar objects in the
      change detection task when they had more time to view the prechange array before
      it switched. Once the cost to using the change detection information decreased,
      subjects made use of it in conjunction with memory to boost performance on the
      familiar-item change detection task. This suggests that even useful information
      will go unused if it is sufficiently difficult to extract.

PMID- 27882525
TI  - Genotyping and Persistence of Candida albicans from Pregnant Women with
      Vulvovaginal Candidiasis.
AB  - OBJECTIVE: To study Candida albicans genotypes using RAPD and their
      susceptibility to fluconazole in healthy pregnant women and in vulvovaginal
      candidiasis (VVC) patients after topical treatment with clotrimazole. METHODS:
      Vaginal swabs were collected at t = 0 and t = 1 (1 month later) in pregnant women
      (control group, n = 33), and before (t = 0), at 1 month (t = 1) and at 2 months
      (t = 2) after clotrimazole treatment in pregnant women with VVC. RESULTS: Candida
      albicans was isolated in 30% of healthy pregnant women and 80% of patients with
      VVC. A high genetic heterogeneity was observed in C. albicans genotypes between
      individuals. In patients with VVC, topical antifungal treatment with clotrimazole
      was clinically effective, but only in a 62% C. albicans was eradicated. In
      patients in which C. albicans was not eradicated, this microorganism persisted
      for 1 or 2 months after the antifungal treatment. The persistent colonies were
      not associated with a specific genotype, but they were associated with higher
      MICs in comparison with colonies isolated from the control group. CONCLUSIONS:
      Therapy with topical clotrimazole, despite a good clinical outcome, could not
      eradicate completely C. albicans allowing the persistence of genotypes, with
      higher MICs to fluconazole. More studies with higher number of patients are
      needed to validate this preliminary finding.

PMID- 27882527
TI  - Diclofenac-Induced Allergic Contact Dermatitis: A Series of Four Patients.
AB  - Allergic contact dermatitis is an immune-mediated antigen-specific skin reaction
      to an allergenic chemical that corresponds to a delayed-type hypersensitivity
      response (type IV reaction). Allergic contact dermatitis should be suspected when
      skin lesions are localized to the site of previous applications of the culprit
      drug. Lesions appear after re-exposure in susceptible persons, with delayed onset
      (more than 24 h after exposure). The gold standard for diagnosis is patch
      (epicutaneous) testing; identification and removal of any potential causal agents
      is crucial. Diclofenac sodium 1% topical gel contains active (diclofenac sodium)
      and inactive ingredients. It is a widely used non-steroidal anti-inflammatory
      drug, known to cause allergic contact dermatitis, and especially photoallergic
      contact reactions. We present four cases of diclofenac-sodium-induced allergic
      contact dermatitis, diagnosed based on clinical grounds: intensively itchy
      eczematous lesions on the sites of drug application after several days of
      treatment. No allergic history and no other drug intake were reported by the
      patients. The application of diclofenac sodium 1% topical gel was strictly
      forbidden in all cases; potent topical steroids proved to be effective in all
      cases within 2 weeks of therapy. Patch tests were performed in all cases with
      European standard battery, with patients' own diclofenac sodium 1% topical gels
      and with diclofenac sodium 1% in petrolatum 3 weeks after completion of local
      steroid therapy. Readings were done after 48 h (Day 2) and 72 h (Day 3) and
      proved to be positive only to patients' diclofenac sodium 1% topical gel and
      diclofenac sodium 1% in petrolatum. No sun exposure was allowed during the
      testing, and any other treatments were forbidden.

PMID- 27882529
TI  - QTL Mapping of Grain Quality Traits Using Introgression Lines Carrying Oryza
      rufipogon Chromosome Segments in Japonica Rice.
AB  - BACKGROUND: Improved eating quality is a major breeding target in japonica rice
      due to market demand. Consequently, quantitative trait loci (QTL) for glossiness
      of cooked rice and amylose content associated with eating quality have received
      much research focus because of their importance in rice quality. RESULTS: In this
      study, QTL associated with 12 grain quality traits were identified using 96
      introgression lines (IL) of rice developed from an interspecific cross between
      the Korean elite O. sativa japonica cultivar 'Hwaseong' and O. rufipogon over 7
      years. QTL analyses indicated that QTL qDTH6 for heading date, detected on
      chromosome 6 is associated with variance in grain traits. Most QTLs detected in
      this study clustered near the qDTH6 locus on chromosome 6, suggesting the effect
      of qDTH6. O. rufipogon alleles negatively affected grain quality traits except
      for a few QTLs, including qGCR9 for glossiness of cooked rice on chromosome 9. To
      characterize the effect of the O. rufipogon locus harboring qGCR9, four lines
      with a single but different O. rufipogon segment near qGCR9 were compared to
      Hwaseong. Three lines (O. rufipopgon ILs) having O. rufipogon segment between
      RM242 and RM245 in common showed higher glossiness of cooked rice than Hwaseong
      and the other line (Hwaseong IL), indicating that qGCR9 is located in the 3.4-Mb
      region between RM242 and RM245. Higher glossiness of cooked rice conferred by the
      O. rufipogon allele might be associated with protein content considering that
      three lines had lower protein content than Hwaseong (P < 0.1). These three O.
      rufipogon ILs showed higher yield than Hwaseong and Hwaseong IL due to increase
      in spikelets per panicle and grain weight indicating the linkage of qGCR9 and
      yield component QTLs. CONCLUSION: The qGCR9 locus is of particular interest
      because of its independence from other undesirable grain quality traits in O.
      rufipogon. SSR markers linked to qGCR9 can be used to develop high-quality
      japonica lines and offer a starting point for map-based cloning of genes
      underlying this trait. To our knowledge, this is the first report to map a
      beneficial QTL for glossiness of cooked rice from a wild rice, O. rufipogon.

PMID- 27882528
TI  - An Empirical Comparison of the EQ-5D-5L, DEMQOL-U and DEMQOL-Proxy-U in a Post
      Hospitalisation Population of Frail Older People Living in Residential Aged Care.
AB  - OBJECTIVE: To empirically compare the measurement properties of the DEMQOL-U and
      DEMQOL-Proxy-U instruments to the EQ-5D-5L and its proxy version (CEQ-5D-5L) in a
      population of frail older people living in residential aged care in the post
      hospitalisation period following a hip fracture. METHODS: A battery of
      instruments to measure health-related quality of life (HRQoL), cognition, and
      clinical indicators of depression, pain and functioning were administered at
      baseline and repeated at 4 weeks' follow-up. Descriptive summary statistics were
      produced and psychometric analyses were conducted to assess the levels of
      agreement, convergent validity and known group validity between clinical
      indicators and HRQoL measures. RESULTS: There was a large divergence in mean (SD)
      utility scores at baseline for the EQ-5D-5L and DEMQOL-U [EQ-5D-5L mean 0.21
      (0.19); DEMQOL-U mean 0.79 (0.14)]. At 4 weeks' follow-up, there was a marked
      improvement in EQ-5D-5L scores whereas DEMQOL-U scores had deteriorated. [EQ-5D
      5L mean 0.45 (0.38); DEMQOL-U mean 0.58 (0.38)]. The EQ-5D and CEQ-5D-5L were
      more responsive to the physical recovery trajectory experienced by frail older
      people following surgery to repair a fractured hip, whereas the DEMQOL-U and
      DEMQOL-Proxy-U appeared more responsive to the changes in delirium and dementia
      symptoms often experienced by frail older people in this period. CONCLUSIONS:
      This study presents important insights into the HRQoL of a relatively under
      researched population of post-hospitalisation frail older people in residential
      care. Further research should investigate the implications for economic
      evaluation of self-complete versus proxy assessment of HRQoL and the choice of
      preference-based instrument for the measurement and valuation of HRQoL in older
      people exhibiting cognitive decline, dementia and other co-morbidities.

PMID- 27882530
TI  - Effect of Dispersion Method on Stability and Dielectric Strength of Transformer
      Oil-Based TiO2 Nanofluids.
AB  - Dispersion stability of nanoparticles in the liquid media is of great importance
      to the utilization in practice. This study aims to investigate the effects of
      mechanical dispersion method on the dispersibility of functionalized TiO2
      nanoparticles in the transformer oil. Dispersion methods, including stirring,
      ultrasonic bath, and probe processes, were systematically tested to verify their
      versatility for preparing stable nanofluid. The test results reveal that the
      combination of ultrasonic bath process and stirring method has the best
      dispersion efficiency and the obtained nanofluid possesses the highest AC
      breakdown strength. Specifically, after aging for 168 h, the size of
      nanoparticles in the nanofluid prepared by the combination method has no obvious
      change, while those obtained by the other three paths are increased obviously.

PMID- 27882531
TI  - Solution-Processed Hybrid Light-Emitting Devices Comprising TiO2 Nanorods and WO3
      Layers as Carrier-Transporting Layers.
AB  - The goal of this research is to prepare inverted light-emitting devices with
      improved performance by combining titanium dioxide (TiO2) nanorods and tungsten
      trioxide (WO3) layer. TiO2 nanorods with different lengths were established
      directly on the fluorine-doped tin oxide (FTO) substrates by the hydrothermal
      method. The prepared TiO2 nanorods with lengths shorter than 200 nm possess
      transmittance higher than 80% in the visible range. Inverted light-emitting
      devices with the configuration of FTO/TiO2 nanorods/ionic PF/MEH
      PPV/PEDOT:PSS/WO3/Au were constructed. The best device based on 100-nm-height
      TiO2 nanorods achieved a max brightness of 4493 cd/m2 and current efficiency of
      0.66 cd/A, revealing much higher performance compared with those using TiO2
      compact layer or nanorods with longer lengths as electron-transporting layers.

PMID- 27882533
TI  - A novel RAD21 variant associated with intrafamilial phenotypic variation in
      Cornelia de Lange syndrome - review of the literature.
AB  - In a patient with CdLS (IV.16) we identifed a novel single basepair deletion
      (c.704delG) in RAD21, which encodes a cohesin pathway protein. The variant is
      predicted to result in a premature stop codon [p.(Ser235Ilefs*19)] and hereby
      would have a deleterious effect. RAD21 variants have previously been described
      only in five cases with cohesinopathies (b). Notably, the deletion was found in
      the mother and the two aunts of the index patient, and none of them had been
      suspected of having CdLS or a cohesinopathy prior to this study (a). The index
      patient can be classified as mild CdLS, but the other family members do not
      fulfill the diagnostic criteria of CdLS. This study together with previous
      reports suggests incomplete penetrance associated with RAD21 variants and these
      individuals may therefore be underdiagnosed.

PMID- 27882532
TI  - Alemtuzumab Use in Clinical Practice: Recommendations from European Multiple
      Sclerosis Experts.
AB  - Alemtuzumab (LemtradaTM) is a humanized monoclonal antibody approved in more than
      50 countries. Within the European Union, alemtuzumab is indicated for the
      treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS)
      with active disease defined by clinical or imaging features; in the USA, the
      indication states that alemtuzumab should generally be reserved for the treatment
      of patients with relapsing forms of multiple sclerosis who have had an inadequate
      response to two or more disease-modifying therapies (DMTs). In clinical trials,
      alemtuzumab demonstrated efficacy in treatment-naive patients with active RRMS
      and those relapsing on prior DMTs, with a consistent and manageable safety and
      tolerability profile. The European Union indication provides physicians with
      significant flexibility regarding treatment decisions, affording the opportunity
      for individualized treatment. Thus, alemtuzumab may be an appropriate treatment
      choice across a broad range of patients with RRMS, including, for example,
      treatment-naive patients with active disease, patients with highly active
      disease, or for patients relapsing on prior DMTs. There are several
      practicalities to consider when using alemtuzumab, including the unique dosing
      regimen, administered via intravenous infusion on 5 consecutive days at baseline
      and on 3 consecutive days 12 months later, and as-needed retreatment (3
      consecutive days at least 12 months after the last course) in cases of disease
      recurrence. Additionally, routine monthly monitoring is required for up to 48
      months after the last infusion to promptly identify potentially serious
      autoimmune adverse events. Given these considerations, it is beneficial to gain
      insight into how alemtuzumab is being used in the real-world clinical setting.
      Here, we report recommendations from European multiple sclerosis experts
      regarding best practices for alemtuzumab treatment, including management of
      adverse events and compliance with ongoing safety monitoring requirements.

PMID- 27882534
TI  - Digest: Hybridizing in a big way.

PMID- 27882535
TI  - Evaluation of three unchannelled videolaryngoscopes and the Macintosh
      laryngoscope in patients with a simulated difficult airway: a randomised,
      controlled trial.
AB  - This prospective randomised, controlled trial compares the performance of three
      unchannelled videolaryngoscopes (KingVisionTM , AirtraqTM , A.P. AdvanceTM MAC)
      and the standard Macintosh laryngoscope. With ethics committee approval and
      written informed consent, 480 patients were included. A difficult airway was
      created with a cervical collar, limiting mouth opening and neck movement. Primary
      outcome was first-attempt orotracheal intubation success. Overall success,
      laryngeal view, intubation difficulty scale, handling, intubation times and side
      effects were secondary outcomes. First-attempt success rates were: KingVision 90%
      (95% CI 83-94%), Airtraq 82% (74-88%), A.P. Advance MAC 49% (40-58%), Macintosh
      44% (35-53%; p < 0.001). The 95% confidence interval of first-attempt success
      rate was thus below 90% for all devices, but the KingVision and the Airtraq
      performed better than the A.P. Advance MAC and the Macintosh laryngoscope. Also,
      performance was better with the KingVision and the Airtraq in terms of overall
      success, laryngeal view, intubation difficulty scale and quality of view.
      Problems with tube advancement were a frequent cause of intubation failure. In
      summary, the KingVision and the Airtraq performed better than the A.P. Advance
      MAC and the Macintosh laryngoscope. Success rates of the unchannelled KingVision
      and Airtraq were similar to those of their channelled versions reported
      previously, indicating that performance largely depends on blade design rather
      than the presence of a channel for tube advancement.

PMID- 27882536
TI  - BRCA1 and BRCA2 mutation testing in Cyprus; a population based study.
AB  - This paper presents the largest study in Cyprus evaluating the frequency and
      distribution of BRCA1/2 mutations in a high risk patient cohort. Deleterious
      mutations in the BRCA1/2 genes were identified in 68 of the 527 patients tested
      (13%). It is of interest that a quarter of those tested positive, did not have an
      extensive family history of breast/ovarian cancer but were diagnosed with early
      onset breast cancer, ovarian cancer under the age of 60 or triple negative breast
      cancer. The spectrum of mutations identified in our patient cohort is different
      compared to other Mediterranean countries. Furthermore, several of the mutations
      detected are novel and have not been identified in other ethnic populations. This
      highlights the importance of operating a national reference center for cancer
      genetic diagnosis which offers services tailored to the needs of the Cypriot
      population.

PMID- 27882537
TI  - Neurochemical and behavioural effects of hypidone hydrochloride (YL-0919): a
      novel combined selective 5-HT reuptake inhibitor and partial 5-HT1A agonist.
AB  - BACKGROUND AND PURPOSE: Our previous studies revealed that hypidone hydrochloride
      (YL-0919), which acts as a selective 5-HT (serotonin) reuptake inhibitor (SSRI)
      and displays partial 5-HT1A receptor agonist properties, exerts a significant
      antidepressant effect in various animal models. The aim of present research was
      to further investigate the pharmacology of YL-0919. EXPERIMENTAL APPROACH: We
      first investigated the target profile of YL-0919 using [35 S]-GTPgammaS binding
      and microdialysis. To determine whether the 5-HT or noradrenergic systems are
      involved in the antidepressant-like effect of YL-0919, the 5-hydroxytryptophan (5
      HTP)-induced head-twitch test and antagonism with a high dose of apomorphine were
      performed. Using the learned helplessness paradigm, the novelty suppressed
      feeding test, the Vogel-type conflict and elevated plus-maze test, we further
      verified the antidepressant-like and anxiolytic-like effects of YL-0919. The
      effects of YL-0919 on hippocampal long-term potentiation (LTP) and sexual
      behaviour were also evaluated. KEY RESULTS: Data from the present study
      demonstrated that YL-0919 displays partial 5-HT1A receptor agonist properties,
      producing a greater impact on extracellular 5-HT levels than a conventional SSRI
      (fluoxetine), as well as significant antidepressant and anxiolytic effects.
      Furthermore, YL-0919 treatment rapidly influenced the synaptic plasticity
      (enhancing LTP) of rats. Finally, at doses close to those producing
      antidepressant-like effects, YL-0919 did not result in a marked inhibition of
      sexual function. CONCLUSIONS AND IMPLICATIONS: These data suggest that YL-0919 is
      probably a fast-onset potent antidepressant with few side effects.

PMID- 27882539
TI  - In vitro suppression of two different stop codons.
AB  - Proteins play a crucial role in all living organisms, with the 20 natural amino
      acids as their building blocks. Unnatural amino acids are synthetic derivatives
      of these natural building blocks. These amino acids have unique chemical or
      physical properties as a result of their specific side chain residues. Their
      incorporation into proteins through ribosomal translation in response to one of
      the stop codons has opened a new way to manipulate and study proteins by enabling
      new functionalities, thus expending the genetic code. Different unnatural amino
      acids have different functionalities, hence, the ability to incorporate two
      different unnatural amino acids, in response to two different stop codons into
      one protein is a useful tool in protein manipulation. This ability has been
      achieved previously only in in vivo translational systems, however, with limited
      functionality. Herein, we report the incorporation of two different unnatural
      amino acids in response to two different stop codons into one protein, utilizing
      a cell-free protein synthesis system. Biotechnol. Bioeng. 2017;114: 1065-1073.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27882538
TI  - Gene therapy with mesenchymal stem cells expressing IFN-beta ameliorates
      neuroinflammation in experimental models of multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: Recombinant IFN-beta is one of the first-line treatments
      in multiple sclerosis (MS), despite its lack of efficacy in some patients. In
      this context, mesenchymal stem cells (MSCs) represent a promising therapeutic
      alternative due to their immunomodulatory properties and multipotency. Moreover,
      by taking advantage of their pathotropism, these cells can be genetically
      modified to be used as carriers for delivering or secreting therapeutic drugs
      into injured tissues. Here, we report the therapeutic effect of systemic delivery
      of adipose-derived MSCs (AdMSCs), transduced with the IFN-beta gene, into mice
      with experimental autoimmune encephalomyelitis (EAE). EXPERIMENTAL APPROACH:
      Relapsing-remitting and chronic progressive EAE were induced in mice. Cells were
      injected i.v. Disease severity, inflammation and tissue damage were assessed
      clinically, by flow cytometry of spleens and histopathological evaluation of the
      CNS respectively. KEY RESULTS: Genetic engineering did not modify the biological
      characteristics of these AdMSCs (morphology, growth rate, immunophenotype and
      multipotency). Furthermore, the transduction of IFN-beta to AdMSCs maintained
      and, in some cases, enhanced the functional properties of AdMSCs by ameliorating
      the symptoms of MS in EAE models and by decreasing indications of peripheral and
      central neuro-inflammation. CONCLUSION AND IMPLICATIONS: Gene therapy was found
      to be more effective than cell therapy in ameliorating several clinical
      parameters in both EAE models, presumably due to the continuous expression of IFN
      beta. Furthermore, it has significant advantages over AdMSC therapy, and also
      over systemic IFN-beta treatment, by providing long-term expression of the
      cytokine at therapeutic concentrations and reducing the frequency of injections,
      while minimizing dose-limiting side effects.

PMID- 27882540
TI  - Does size matter? Examining the drivers of mammalian vocalizations.
AB  - Previous studies of the vocalization frequencies of mammals have suggested that
      it is either body mass or environment that drives these frequencies. Using 193
      species across the globe from the terrestrial and aquatic environments and a
      model selection approach, we identified that the best-supported model for minimum
      and maximum frequencies for vocalization included both body mass and environment.
      The minimum frequencies of vocalizations of species from all environments
      retained the influence of body mass. For maximum frequency however, aquatic
      species are released from such a trend with body mass having little constraint on
      frequencies. Surprisingly, phylogeny did not have a strong impact on the
      evolution of the maximum frequency of mammal vocalizations, largely due to the
      pinniped species divergence of frequency from their carnivoran relatives. We
      demonstrate that the divergence of signal frequencies in mammals has arisen from
      the need to adapt to their environment.

PMID- 27882541
TI  - Prediction of difficult mask ventilation using a systematic assessment of risk
      factors vs. existing practice - a cluster randomised clinical trial in 94,006
      patients.
AB  - We compared implementation of systematic airway assessment with existing practice
      of airway assessment on prediction of difficult mask ventilation. Twenty-six
      departments were cluster-randomised to assess eleven risk factors for difficult
      airway management (intervention) or to continue with their existing airway
      assessment (control). In both groups, patients predicted as a difficult mask
      ventilation and/or difficult intubation were registered in the Danish Anaesthesia
      Database, with a notational summary of airway management. The trial's primary
      outcome was the respective incidence of unpredicted difficult and easy mask
      ventilation in the two groups. Among 94,006 patients undergoing mask ventilation,
      the incidence of unpredicted difficult mask ventilation in the intervention group
      was 0.91% and 0.88% in the control group; (OR) 0.98 (95% CI 0.66-1.44), p = 0.90.
      The incidence of patients predicted difficult to mask ventilate, but in fact
      found to be easy ('falsely predicted difficult') was 0.64% vs. 0.35%
      (intervention vs. control); OR 1.56 (1.01-2.42), p = 0.045. In the intervention
      group, 86.3% of all difficult mask ventilations were not predicted, compared with
      a higher proportion 91.2% in the control group, OR 0.61 (0.41-0.91), p = 0.016.
      The systematic intervention did not alter the overall incidence of unpredicted
      difficult mask ventilations, but of the patients who were found to be difficult
      to mask ventilate, the proportion predicted was higher in the intervention group
      than in the control group. However, this was at a 'cost' of increasing the number
      of mask ventilations falsely predicted to be difficult.

PMID- 27882542
TI  - A novel gain-of-function mutation in ORAI1 causes late-onset tubular aggregate
      myopathy and congenital miosis.
AB  - We present three members of an Italian family affected by tubular aggregate
      myopathy (TAM) and congenital miosis harboring a novel missense mutation in
      ORAI1. All patients had a mild, late onset TAM revealed by asymptomatic creatine
      kinase (CK) elevation and congenital miosis consistent with a Stormorken-like
      Syndrome, in the absence of thrombocytopathy. Muscle biopsies showed classical
      histological findings but ultrastructural analysis revealed atypical tubular
      aggregates (TAs). The whole body muscle magnetic resonance imaging (MRI) showed a
      similar pattern of muscle involvement that correlated with clinical severity. The
      lower limbs were more severely affected than the scapular girdle, and thighs were
      more affected than legs. Molecular analysis revealed a novel c.290C>G (p.S97C)
      mutation in ORAI1 in all affected patients. Functional assays in both human
      embryonic kidney (HEK) cells and myotubes showed an increased rate of Ca2+ entry
      due to a constitutive activation of the CRAC channel, consistent with a 'gain-of
      function' mutation. In conclusion, we describe an Italian family harboring a
      novel heterozygous c.290C>G (p.S97C) mutation in ORAI1 causing a mild- and late
      onset TAM and congenital miosis via constitutive activation of the CRAC channel.
      Our findings extend the clinical and genetic spectrum of the ORAI1-related TAM.

PMID- 27882543
TI  - Sampling for Patient Exit Interviews: Assessment of Methods Using Mathematical
      Derivation and Computer Simulations.
AB  - OBJECTIVE: (1) To evaluate the operational efficiency of various sampling methods
      for patient exit interviews; (2) to discuss under what circumstances each method
      yields an unbiased sample; and (3) to propose a new, operationally efficient, and
      unbiased sampling method. STUDY DESIGN: Literature review, mathematical
      derivation, and Monte Carlo simulations. PRINCIPAL FINDINGS: Our simulations show
      that in patient exit interviews it is most operationally efficient if the
      interviewer, after completing an interview, selects the next patient exiting the
      clinical consultation. We demonstrate mathematically that this method yields a
      biased sample: patients who spend a longer time with the clinician are
      overrepresented. This bias can be removed by selecting the next patient who
      enters, rather than exits, the consultation room. We show that this sampling
      method is operationally more efficient than alternative methods (systematic and
      simple random sampling) in most primary health care settings. CONCLUSION: Under
      the assumption that the order in which patients enter the consultation room is
      unrelated to the length of time spent with the clinician and the interviewer,
      selecting the next patient entering the consultation room tends to be the
      operationally most efficient unbiased sampling method for patient exit
      interviews.

PMID- 27882544
TI  - Prospective evaluation of the Ages and Stages Questionnaire 3rd Edition in very
      low-birthweight infants.
AB  - AIM: To evaluate the predictive and concurrent diagnostic agreement of the Ages
      and Stages Questionnaire 3rd Edition (ASQ-3) with the Bayley Scales of Infant and
      Toddler Development 3rd Edition (Bayley-III) in infants born preterm and very-low
      birthweight (PT/VLBW; <=1250g). METHOD: We evaluated 141 PT/VLBW infants (68
      males, 73 females) born at the KK Women's and Children's Hospital between January
      2010 and December 2011, to determine predictive and concurrent diagnostic
      agreement between the ASQ-3 at 9, 12, 18, and 24 months corrected age and Bayley
      III at 24 months. Cut-offs on the ASQ-3 at 24 months were estimated by receiver
      operating characteristic curves. RESULTS: Sixty (43%) and 25 (18%) failed in any
      domain of the ASQ-3 and Bayley-III (<70) respectively. A negative predictive
      value (NPV) >98% was achieved for the motor domain from 9 months, and >90% for
      the communication domain and the overall results at 24 months. Optimal referral
      ASQ-3 score at 24 months to achieve 100% NPV was 243. INTERPRETATION: In PT/VLBW
      infants, ASQ-3 screening at 24 months can reduce the need for costly psychometric
      assessments in children with normal results. Clinicians can be assured of normal
      motor development at 9 months using the ASQ-3, but should continue to screen
      children on other domains.

PMID- 27882545
TI  - Low abundant soil bacteria can be metabolically versatile and fast growing.
AB  - The abundance of species is assumed to depend on their life history traits, such
      as growth rate and resource specialization. However, this assumption has not been
      tested for bacteria. Here we investigate how abundance of soil bacteria relates
      to slow growth and substrate specialization (oligotrophy) vs. fast growth and
      substrate generalization (copiotrophy). We collected 47 saprotrophic soil
      bacterial isolates of differing abundances and measured their growth rate and the
      ability to use a variety of single carbon sources. Opposite to our expectation,
      there was no relationship between abundance in soil and the measured growth rate
      or substrate utilization profile (SUP). However, isolates with lower growth rates
      used fewer substrates than faster growing ones supporting the assumption that
      growth rate may relate to substrate specialization. Interestingly, growth rate
      and SUP were correlated with phylogeny, rather than with abundance in soil. Most
      markedly, Gammaproteobacteria on average grew significantly faster and were able
      to use more substrates than other bacterial classes, whereas Alphaproteobacteria
      were growing relatively slowly and used fewer substrates. This finding suggests
      that growth and substrate utilization are phylogenetically deeply conserved. We
      conclude that growth rate and substrate utilization of soil bacteria are not
      general determinants of their abundance. Future studies on explaining bacterial
      abundance need to determine how other factors, such as competition, predation and
      abiotic factors may contribute to rarity or abundance in soil bacteria.

PMID- 27882547
TI  - Molecular characterization of PI*Q0la palma , a new alpha-1-antitrypsin null
      allele that combines two defective genetic variants.

PMID- 27882546
TI  - Human gingival fibroblasts induced and differentiated into vascular endothelial
      like cells.
AB  - A novel method for repair of vascular disease, mechanical damage, and tissue
      rebuilding is urgently required. Vascular endothelial cells (VECs) play an
      essential role in vascular rebuilding and vasotransplantation. In the present
      study, human gingival fibroblasts (HGFs) were cultured and induced into
      endothelial-like cells in vitro in order to confirm that HGFs with stem cell
      properties possessed the potential for differentiation into endothelial-like
      cells. The epithelium was extracted from normal human gingiva consisting of
      epithelium and connective tissue, which was isolated from patients. The
      identification of HGFs and induced endothelial-like cells were confirmed by flow
      cytometry, reverse transcription polymerase chain reaction (RT-PCR),
      immunocytochemical stain (ICS), and immunofluorescence stain (ISA). The
      morphology of human gingival fibroblasts with 8 ng/mL VEGF165 induced for
      different periods of days were observed by inverted microscope. Before induction,
      flow cytometry analysis showed that HGFs were positive for vimentin, but negative
      for CD31. RT-PCR, ICS, and ISA showed vimentin, S100A4, alpha-SMA, collagen III,
      and S100A4 were specifically expressed in these fibroblast cells. After
      induction, ICS showed induced vascular endothelial-like cells were positive for
      CD34 and CD31; ISA showed cells induced were positive for vWF and E-cadherin; RT
      PCR results demonstrated that tie2 was specifically expressed in the cells
      induced. Flow cytometry analysis of the transformation efficiency from HGFs to
      endothelial-like cells. In conclusion, we found that HGFs possessed capacity for
      being induced and differentiated into vessel endothelial-like cells with typical
      and specific morphological, ultrastructural, and immunological characters of
      endothelial-like cells by induction with VEGF.

PMID- 27882548
TI  - Making a Bad Diagnosis Worse? Suspect Drug Management of Urinary Incontinence in
      Persons with Dementia.

PMID- 27882549
TI  - Digest: Mechanisms of assortative mating and ecological speciation.

PMID- 27882551
TI  - Digest: Fitness gains in guppies support evolution's role in coexistence.

PMID- 27882552
TI  - Trends and the utilization of transoral robotic surgery with neck dissection in
      New York State.
AB  - OBJECTIVES: The timing of neck dissection (ND) in relation to transoral robotic
      surgery (TORS) is controversial. This study identifies local practice patterns
      and economic and social access disparities during adoption of TORS. STUDY DESIGN:
      We analyzed utilization patterns of TORS and ND using the New York Statewide
      Planning and Research Cooperative System all-payer administrative database.
      Statewide head and neck cancer incidence from the Centers for Disease Control and
      Prevention (Bethesda, MD) was used to control for overall cancer incidence.
      METHODS: Patient demographic, insurer, and institutional information of patients
      aged >= 18 (n = 225) years from 2008 to 2012 were evaluated. Temporal trends were
      analyzed with Poisson regression models for counts. RESULTS: Transoral robotic
      surgery was used in 386 procedures, and 58.3% involved ND (n = 225). Concurrent
      ND was most frequent (n = 173), followed by staged TORS then ND (n = 44) and
      staged ND preceding TORS (n = 8). Caucasians were more likely than
      Blacks/Hispanics to undergo TORS (P = 0.03). Medicare (26.2%) and Medicaid (2.7%)
      payers comprised a minority of patients compared to those commercially insured
      (70.2%). Only 20% of patients received care outside a major urban center, and
      these patients were more likely to undergo staged procedures, P = 0.02. Staged
      procedures resulted in higher mean hospital charges (P = 0.02). CONCLUSION:
      Concurrent TORS + ND, the most common practice in New York, is more cost
      effective. Patients without commercial insurance, patients in racial minorities,
      or patients residing outside major urban centers may be targeted to improve care
      access disparities with respect to minimally invasive TORS technology. LEVEL OF
      EVIDENCE: 2c. Laryngoscope, 127:1571-1576, 2017.

PMID- 27882550
TI  - Investigating interactions between epicardial adipose tissue and cardiac
      myocytes: what can we learn from different approaches?
AB  - : Heart disease is a major cause of morbidity and mortality throughout the world.
      Some cardiovascular conditions can be modulated by lifestyle factors such as
      increased exercise or a healthier diet, but many require surgical or
      pharmacological interventions for their management. More targeted and less
      invasive therapies would be beneficial. Recently, it has become apparent that
      epicardial adipose tissue plays an important role in normal and pathological
      cardiac function, and it is now the focus of considerable research. Epicardial
      adipose tissue can be studied by imaging of various kinds, and these approaches
      have yielded much useful information. However, at a molecular level, it is more
      difficult to study as it is relatively scarce in animal models and, for practical
      and ethical reasons, not always available in sufficient quantities from patients.
      What is needed is a robust model system in which the interactions between
      epicardial adipocytes and cardiac myocytes can be studied, and physiologically
      relevant manipulations performed. There are drawbacks to conventional culture
      methods, not least the difficulty of culturing both cardiac myocytes and
      adipocytes, each of which has special requirements. We discuss the benefits of a
      three-dimensional co-culture model in which in vivo interactions can be
      replicated. LINKED ARTICLES: This article is part of a themed section on
      Molecular Mechanisms Regulating Perivascular Adipose Tissue - Potential
      Pharmacological Targets? To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.20/issuetoc.

PMID- 27882553
TI  - Malignant otitis externa hospitalizations: Analysis of patient characteristics.
AB  - OBJECTIVES/HYPOTHESIS: Malignant otitis externa (MOE) is a rare disorder that is
      not well studied in the inpatient setting. The Nationwide Inpatient Sample (NIS)
      database was utilized to analyze characteristics and predischarge outcomes of
      hospitalized MOE patients. METHODS: MOE hospitalizations were identified in the
      2002 to 2013 NIS. Patient demographics, length of hospital stay, hospital
      charges, concomitant diagnoses, treatment-related procedures, complications, and
      in-hospital mortality rates were examined, with comparisons made among age
      cohorts and between diabetes mellitus (DM) and non-DM groups. RESULTS: A total of
      8,300 cases of inpatient MOE were identified, with elderly DM patients
      compromising 22.7% of cases. Compared to adults, elderly patients had more
      inpatient procedures, longer hospitalizations (6.0 vs. 4.3 days), higher hospital
      charges ($26,712 vs. $19,047) (all P < 0.001), greater odds of in-hospital
      complications, and in-hospital mortality (odds ratio 14.435, 95% confidence
      interval 5.313-39.220). Adult/elderly patients with DM had more comorbidities,
      longer hospital stays (5.5 vs. 4.0 days), and higher hospital charges ($25,118
      vs. $17,039) (all P < 0.001) than non-DM patients. However, DM was not associated
      with greater in-hospital mortality rates (0.6% vs. 0.5%; P = 0.640). Compared to
      the adult/elderly cohort, pediatric patients had higher rates of nonelective
      admissions (19.8% vs. 14.5%), shorter hospital stays (2.9 vs. 4.9 days), and
      lower hospital charges ($8,876 vs. $21,672) (all P < 0.05). CONCLUSION: Elderly
      diabetic patients made up a smaller fraction of hospitalized MOE cases than
      anticipated. Elderly patients had greater in-hospital complications and
      mortality. Diabetes mellitus in adult/elderly patients was not associated with
      increased mortality. Pediatric patients fared well with low complications rates
      and no instances of in-hospital mortality. LEVEL OF EVIDENCE: 2C. Laryngoscope,
      127:2328-2336, 2017.

PMID- 27882554
TI  - Study of heat-moisture treatment of potato starch granules by chemical surface
      gelatinization.
AB  - BACKGROUND: Native potato starch was subjected to heat-moisture treatment (HMT)
      at 12%, 15%, 18%, 21%, and 24% of moisture content at 110  degrees C for 1 h, and
      the effects on morphology, structure, and thermal and physicochemical properties
      were investigated. To reveal the internal structure, 30% and 50% of the granular
      surface were removed by chemical surface gelatinization in concentrated LiCl
      solution. RESULTS: At moisture contents of 12% and 15%, HTM reduced the
      gelatinization temperatures and relative crystallinity of the starches, while at
      moisture contents of 21% and 24 % both increased. The alterations on morphology,
      X-ray pattern, physicochemical properties, and increase of amylose content were
      more intense with the increase of moisture content of HMT. CONCLUSION: The
      removal of granular layers showed that the changes promoted by HMT occur
      throughout the whole granule and were pronounced at the core or peripheral
      region, depending of the moisture content applied during HMT. (c) 2016 Society of
      Chemical Industry.

PMID- 27882555
TI  - A randomized controlled pilot study of VO2 max testing: a potential model for
      measuring relative in vivo efficacy of different red blood cell products.
AB  - BACKGROUND: Randomized trials, for example, RECESS, comparing "young" (median, 7
      day) versus "middle-aged" (median, 28-day) red blood cells (RBCs), showed no
      difference in outcome. These data are important; however, they do not inform us
      about the safety and effectiveness of the oldest RBCs, which some patients
      receive. It may not be feasible to conduct a clinical trial randomizing patients
      to receive the oldest blood. Therefore, we propose strenuous exercise (VO2 max
      testing) as a model to study the relative efficacy to increase oxygen delivery to
      tissue of different RBC products, for example, extremes of storage duration.
      STUDY DESIGN AND METHODS: In this pilot study, eight healthy subjects had 2 units
      of leukoreduced RBCs collected by apheresis in AS-3 using standard methods.
      Subjects were randomized to receive both (2) units of their autologous RBCs at
      either 7 or 42 days after blood collection. VO2 max testing on a cycle ergometer
      was performed 2 days before (Monday) and 2 days after (Friday) the transfusion
      visit (Wednesday). This design avoids confounding effects on intravascular volume
      from the 2-unit blood transfusion. The primary outcome was the difference in VO2
      max between Friday and Monday (delta VO2 max). RESULTS: VO2 max increased more in
      the 7-day RBC arm (8.7 +/- 6.9% vs. 1.9 +/- 6.5%, p = 0.202 for comparison
      between arms). Exercise duration (seconds) increased in the 7-day RBC arm (8.4 +/
      1.7%) but actually decreased in the 42-day arm (-2.6 +/- 3.6%, p = 0.002).
      CONCLUSIONS: This pilot study suggests that VO2 max testing has potential as a
      rigorous and quantitative in vivo functional assay of RBC function. Our
      preliminary results suggest that 42-day RBCs are inferior to 7-day RBCs at
      delivering oxygen to tissues.

PMID- 27882556
TI  - 3D analysis of the movements of the laryngeal cartilages during singing.
AB  - OBJECTIVE: The vocal range of untrained singers rarely exceeds one and a half
      octaves, but professional singers have a range of at least two and a half
      octaves. The aim of this study was to better understand the muscle and cartilage
      movements responsible for the control of vocal pitch in singing. STUDY DESIGN:
      Prospective study. METHODS: We recruited 49 female professional singers (25
      sopranos and 24 altos) and analyzed laryngeal three-dimensional images derived
      from high-resolution computed tomography scans obtained at the mean speaking
      fundamental frequency (F0) and at one (F1) and two octaves (F2) above this pitch.
      RESULTS: From F0 to F1, the only observable movement was a backward cricoid
      tilting caused by the cricothyroid muscles (CTMs), leading to vocal fold
      stretching. Above F1, a medial rotation and inward rocking of the arytenoid
      cartilages was observed, caused by the lateral cricothyroid muscles (LCAMs) and
      leading to inferior displacement of the vocal process of the arytenoid cartilage,
      and thus to further vocal fold stretching. CONCLUSION: Trained singers achieve
      the first octave of pitch elevation by simple cricothyroid approximation. Further
      pitch elevation necessitates a complex movement of the arytenoids, first by CTM
      contraction and second by LCAM contraction. LEVEL OF EVIDENCE: 4. Laryngoscope,
      127:1639-1643, 2017.

PMID- 27882557
TI  - Laboratory-scale milling of whole-durum flour quality: effect of mill
      configuration and seed conditioning.
AB  - BACKGROUND: Research was conducted to develop a laboratory milling procedure to
      make whole-durum flour. An ultracentrifugal mill was evaluated by determining the
      effect of mill configuration and seed conditioning on particle size distribution
      and quality of whole-wheat flour. RESULTS: Particle size of whole-wheat flour
      decreased as screen aperture decreased from 1000 to 250 um; as rotor speed
      increased from 6000 to 18 000 rpm; and as seed conditioning moisture content
      decreased from 150 to 90 g kg-1 . Feed rate during milling did not affect
      particle size distribution. Starch damage decreased as screen aperture increased;
      as rotor speed increased from 6000 to12 000 rpm; and as seed conditioning
      moisture content decreased from 150 to 90 g kg-1 . Flour temperature varied with
      milling parameters but did not exceed 34  degrees C. CONCLUSION: An
      ultracentrifugal mill configured with a rotor speed of 12 000 rpm, screen
      aperture of 250 um, and seed conditioning moisture of 90 g kg-1 resulted in a
      fine whole-wheat flour where 82% of particles were <150 um, starch damage was 59
      g kg-1 , and flour temperature was below 35  degrees C. (c) 2016 Society of
      Chemical Industry.

PMID- 27882559
TI  - Lipiodol does not affect the tissue distribution of intravenous doxorubicin
      infusion in pigs.
AB  - OBJECTIVES: In liver cancer treatment, lipiodol is used as a pharmaceutical
      excipient to improve delivery of the cytostatic drug doxorubicin (DOX). As DOX
      and its metabolite doxorubicinol (DOXol) cause serious off-target adverse
      effects, we investigated the effects of drug-free lipiodol or ciclosporin (CsA)
      on the tissue distribution (Kp ) of DOX and DOXol in relevant pig tissues.
      METHODS: Four treatment groups (TI-TIV) all received an intravenous DOX solution
      at 0 and 200 min. Before the second dose, the pigs received a portal vein
      infusion of saline (TI), lipiodol (TII), CsA (TIII) or lipiodol and CsA (TIV).
      After 6 h, the pigs were euthanised, and liver, kidney, heart and intestine
      samples were collected and analysed. KEY FINDINGS: The tissue DOX concentrations
      were highest in the kidney (TI-TIV). All the investigated tissues showed
      extensive DOX Kp . Lipiodol had no effect on the Kp of DOX to any of the tissues.
      However, the tissue concentrations of DOX were increased by CsA (in liver, kidney
      and intestine, P < 0.05). CONCLUSION: Lipiodol injected into the portal vein does
      not affect the tissue distribution of DOX and DOXol.

PMID- 27882560
TI  - A Computer Prescribing Order Entry-Clinical Decision Support system designed for
      neonatal care: results of the 'preselected prescription' concept at the bedside.
AB  - WHAT IS KNOWN: The neonatal intensive care units (NICUs) are at the highest risk
      of drug dose error of all hospital wards. NICUs also have the most complicated
      prescription modalities. The computerization of the prescription process is
      currently recommended to decrease the risk of preventable adverse drug effects
      (pADEs) in NICUs. However, Computer Prescribing Order Entry-Clinical Decision
      Support (C.P.O.E./C.D.S.) systems have been poorly studied in NICUs, and their
      technical compatibility with neonatal specificities has been limited. OBJECTIVES:
      We set up a performance study of the preselected prescription of drugs for
      neonates, which limited the role of the prescriber to choosing the drugs and
      their indications. METHODS: A single 29 bed neonatal ward used this neonatal
      C.P.O.E./C.D.S. system for all prescriptions of all hospitalized newborns over an
      18-month period. The preselected prescription of drugs was based on the
      indication, gestational age, body weight and post-natal age. The therapeutic
      protocols were provided by a formulary reference (330 drugs) that had been
      specifically designed for newborns. The preselected prescription also gave
      complete information about preparation and administration of drugs by nurses. The
      prescriber was allowed to modify the preselected prescription but alarms provided
      warning when the prescription was outside the recommended range. The main
      clinical characteristics and all items of each line of prescription were stored
      in a data warehouse, thus enabling this study to take place. RESULTS: Seven
      hundred and sixty successive newborns (from 24 to 42 weeks' gestation) were
      prescribed 52 392 lines of prescription corresponding to 65 drugs; About 30.4% of
      neonates had at least one out of licensed prescription; A prescription out of the
      recommended range for daily dose was recorded for 1.0% of all drug prescriptions.
      WHAT IS NEW?: The C.P.O.E./C.D.S. systems can currently provide a complete
      preselected prescription in NICUs according to dose rules, which are specific to
      newborns and also comply with local specificities (therapeutic protocols and
      formulation of drugs). The role of the prescriber is limited to the choice of
      drugs and their indications. The prescriber still retains the possibility of
      modifying each item of the prescription, with all other prescription items being
      calculated by the C.P.O.E. system. In these conditions, the prescribers rarely
      modified the preselected prescription and the rate of out of range prescription
      was low. A multicentric study is required to confirm and extend these
      observations. CONCLUSIONS: This study showed the feasibility of preselected
      prescription in NICUs and a low rate of out of range prescriptions. The
      preselected prescription could play a key role in lowering the dose error rate in
      NICUs.

PMID- 27882561
TI  - Linear regression and correlation.

PMID- 27882558
TI  - Effects of voice-sparing cricotracheal resection on phonation in women.
AB  - INTRODUCTION: Individuals with idiopathic subglottic stenosis (SGS) are at risk
      for voice disorders prior to and following surgical management. This study
      examined the nature and severity of voice disorders in patients with SGS before
      and after a revised cricotracheal resection (CTR) procedure designed to minimize
      adverse effects on voice function. METHOD: Eleven women with idiopathic SGS
      provided presurgical and postsurgical audio recordings. Voice Handicap Index
      (VHI) scores were also collected. Cepstral, signal-to-noise, periodicity, and
      fundamental frequency (F0 ) analyses were undertaken for connected speech and
      sustained vowel samples. Listeners made auditory-perceptual ratings of overall
      quality and monotonicity. RESULTS: Paired samples statistical analyses revealed
      that mean F0 decreased from 215 Hz (standard deviation [SD] = 40 Hz) to 201 Hz
      (SD = 65 Hz) following surgery. In general, VHI scores decreased after surgery.
      Voice disorder severity based on the Cepstral Spectral Index of Dysphonia
      (KayPentax, Montvale, NJ) for sustained vowels decreased (improved) from 41 (SD =
      41) to 25 (SD = 21) points; no change was observed for connected speech. Semitone
      SD (2.2 semitones) did not change from pre- to posttreatment. Auditory-perceptual
      ratings demonstrated similar results. CONCLUSION: These preliminary results
      indicate that this revised CTR procedure is promising in minimizing adverse voice
      effects while offering a longer-term surgical outcome for SGS. Further research
      is needed to determine causal factors for pretreatment voice disorders, as well
      as to optimize treatments in this population. LEVEL OF EVIDENCE: 4. Laryngoscope,
      127:2085-2092, 2017.

PMID- 27882562
TI  - The development and validation of a high-throughput LC-MS/MS method for the
      analysis of endogenous beta-hydroxy-beta-methylbutyrate in human plasma.
AB  - A high-throughput, sensitive, and rugged liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method for the rapid quantitation of beta-hydroxy-beta
      methylbutyrate (HMB) in human plasma has been developed and validated for routine
      use. The method uses 100 MUL of plasma sample and employs protein precipitation
      with 0.1% formic acid in methanol for the extraction of HMB from plasma. Sample
      extracts were analyzed using LC-MS/MS technique under negative mode electrospray
      ionization conditions. A 13 C-labeled stable isotope internal standard was used
      to achieve accurate quantitation. Multiday validation was conducted for
      precision, accuracy, linearity, selectivity, matrix effect, dilution integrity
      (2*), extraction recovery, freeze-thaw sample stability (three cycles), benchtop
      sample stability (6 h and 50 min), autosampler stability (27 h) and frozen
      storage sample stability (146 days). Linearity was demonstrated between 10 and
      500 ng/mL. Inter-day accuracies and coefficients of variation (CV) were 91.2-98.1
      and 3.7-7.8%, respectively. The validated method was proven to be rugged for
      routine use to quantify endogenous levels of HMB in human plasma obtained from
      healthy volunteers.

PMID- 27882563
TI  - Iranian nursing students' perspectives on transition to professional identity: a
      qualitative study.
AB  - AIM: To explore Iranian nursing students' transition to professional identity.
      BACKGROUND: Professional identity is an important outcome of nursing education
      that has not been fully explored in the Iranian nursing education system.
      INTRODUCTION: Professional identity is a significant factor influencing the
      development of nursing education and practice. The transition of nursing students
      to professional identity is the main concern of nursing education and fundamental
      prerequisite for policymaking and planning in the field of nursing education.
      METHODS: This was a qualitative content analysis study. In-depth unstructured
      interviews were held with 35 Iranian bachelor's degree nursing students recruited
      through purposive sampling. The interviews were transcribed verbatim and analysed
      using content analysis. FINDINGS: The data analysis led to the development of
      four themes and 15 categories: 'satisfaction with professional practice
      (attending clinical settings and communicating with patients, the feeling of
      being beneficial)'; 'personal development (growing interest in nursing, feeling
      competent in helping others, changing character and attitude shift towards
      patients)'; 'professional development (realizing the importance of nursing
      knowledge, appreciating professional roles, a changing their understanding of
      nursing and the meaning it)'; and 'attaining professional commitment (a tendency
      to present oneself as a nurse, attempting to change oneself, other students and
      the public image of nursing)'. DISCUSSION: Development of professional identity
      is a continual process of transition. The greatest transition occurred in the
      last year of the programme. CONCLUSION: Nursing students experienced transition
      to PI through gaining satisfaction with professional practice, undergoing
      personal and professional development and developing a professional commitment.
      IMPLICATIONS FOR NURSING AND HEALTH POLICY: Educational policymakers can use our
      findings for developing strategies that facilitate and support nursing students'
      transition to professional identity.

PMID- 27882564
TI  - Processing black mulberry into jam: effects on antioxidant potential and in vitro
      bioaccessibility.
AB  - BACKGROUND: Black mulberries (Morus nigra) were processed into jam on an
      industrialised scale, including the major steps of: selection of frozen black
      mulberries, adding glucose-fructose syrup and water, cooking, adding citric acid
      and apple pectin, removing seeds, and pasteurisation. Qualitative and
      quantitative determinations of antioxidants in black mulberry samples were
      performed using spectrophotometric methods, as well as HPLC- and LC-QTOF-MS-based
      measurements. These analyses included the determination of total polyphenolic
      content, % polymeric colour, total and individual anthocyanin contents,
      antioxidant capacity, and in vitro bioaccessibility in processing samples.
      RESULTS: Jam processing led to a significant reduction in total phenolics (88%),
      total flavonoids (89%), anthocyanins (97%), and antioxidant capacity (88-93%) (P
      < 0.05). Individual anthocyanin contents, determined using HPLC analysis, also
      showed a significant decrease (~99% loss). In contrast, % recovery of
      bioaccessible total phenolics, anthocyanins, and antioxidant capacity (ABTS
      assay) increased after jam processing (16%, 12%, and 37%, respectively).
      CONCLUSION: Fruit processing resulted in losses of polyphenols, anthocyanins, and
      antioxidant capacity of black mulberry jam. Optimisation of food processing could
      help to protect the phenolic compounds in fruits which might be helpful for the
      food industry to minimise the antioxidant loss and improve the final product
      quality. (c) 2016 Society of Chemical Industry.

PMID- 27882565
TI  - Tanshinone IIA attenuates Abeta25-35 -induced spatial memory impairment via
      upregulating receptors for activated C kinase1 and inhibiting autophagy in
      hippocampus.
AB  - OBJECTIVES: Tanshinone IIA (Tan IIA) may exert significant protective effects
      against the neurotoxicity induced by beta-amyloid protein (Abeta). This study was
      designed to investigate the possible neuroprotective mechanism of Tan IIA on
      Abeta25-35 -induced spatial memory impairment in mice. METHODS: After 3 weeks of
      preventive treatment (Tan IIA or oil), all male Kunming mice were subjected to
      Abeta25-35 (10 MUl, intracerebroventricularly (i.c.v.)) to establish the spatial
      memory impairment model. The Morris water maze (MWM), haematoxylin and eosin
      staining, real-time PCR and Western blot were performed to determine the ability
      of spatial memory, neuronal damage and expression of extracellular signal
      regulated kinase (ERK), receptors for activated C kinase1 (RACK1) and autophagy
      related genes. Additionally, ShRACK1 was used to decrease the level of RACK1 in
      the hippocampus to test Beclin1 in hippocampus by real-time PCR and Western blot.
      KEY FINDINGS: Tanshinone IIA (Tan IIA, 80 mg/kg) administration notably protected
      mice from Abeta25-35 -induced spatial memory impairment and neurotoxicity,
      increased pERK/ERK and the expression of RACK1, and reduced the elevated levels
      of BECLIN1 and LC3-II/I in the hippocampus. In addition, ShRACK1 i.c.v markedly
      upregulated BECLIN1 level, but not altered Beclin1 mRNA expression in the
      hippocampus. CONCLUSIONS: Tanshinone IIA may exert neuroprotective effects via
      upregulating RACK1 and inhibiting autophagy in the hippocampus of mice.

PMID- 27882567
TI  - Autoantibodies Directed Against the Endothelin A Receptor in Patients With Benign
      Prostatic Hyperplasia.
AB  - BACKGROUND: Over-stimulation of G-protein coupled receptors (GPCRs) such as
      alpha1-adrenergic, muscarinic, endothelin, and AT1 receptors is considered to
      drive benign prostatic hyperplasia (BHP) which is often associated with lower
      urinary tract syndrome (LUTS). However, in addition to physiologic GPCR ligands,
      there is a new class of autoantibodies called functional autoantibodies that
      target the same GPCRs (GPCR-AABs) for over-stimulation, thus, presenting
      pathogenic potency. We hypothesize that patients with BPH/LUTS could carry GPCR
      AABs representing potential targets for treatment. METHODS: GPCR-AABs were
      identified, quantified, and characterized in the serum from 20 patients (aged 55
      82 years, median 71 years) with BPH using the bioassay of spontaneously beating
      cultured neonatal rat cardiomyocytes. RESULTS: A sum of 60% of the patients were
      positive for agonistic autoantibodies directed against the endothelin A receptor
      (ETA-AABs). ETA-AABs were associated with the IgG 1 subclass, targeted an epitope
      located on the second extracellular receptor loop and their agonistic activity
      could be neutralized by the aptamer BC007. CONCLUSIONS: Agonistic ETA-AABs could
      via uncontrolled over-boarding endothelin A receptor stimulation-contribute to
      the pathogenesis of BPH/LUTS. The in vitro demonstrated ETA-AAB neutralization by
      the aptamer BC007 could open the door for a new treatment strategy in patients
      with BPH/LUTS. Prostate 77:458-465, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27882566
TI  - Angiotensin-converting enzyme inhibitory and antioxidant peptides from digestion
      of larvae and pupae of Asian weaver ant, Oecophylla smaragdina, Fabricius.
AB  - BACKGROUND: Mixed larvae and pupae of weaver ant (Oecophylla smaragdina) are
      widely used as an important food ingredient in regions of Thailand. They have
      high nutritional values and comprise 53% protein and 13% lipid. Peptides derived
      from food proteins have been shown to possess biological activities. RESULTS:
      Peptides derived from pepsin and trypsin digestion of these weaver ant larvae and
      pupae were purified based on angiotensin-converting enzyme (ACE) inhibitory and
      antioxidant activities, and their amino acid sequences were identified by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). In silico docking of peptides
      with ACE successfully predicted the inhibitory peptides as confirmed by their
      chemical synthesis. Two peptides with sequences of FFGT and LSRVP showed IC50
      values for ACE inhibition of 19.5 +/- 1.7 and 52.7 +/- 4.0 umol L-1 ,
      respectively. In addition, one potent antioxidant peptide with a sequence of
      CTKKHKPNC showed IC50 values of 48.2 +/- 2.1 umol L-1 for DPPH assay and 38.4 +/-
      0.2 umol L-1 for ABTS assay, respectively. CONCLUSION: These results indicate
      that proteins from larvae and pupae of weaver ants are potential sources of
      peptides with anti-ACE and antioxidation bioactivities. (c) 2016 Society of
      Chemical Industry.

PMID- 27882568
TI  - The evolution of weak standards: the case of the Swedish rheumatology quality
      registry.
AB  - Research in sociology suggests that the effects of standards are not nearly as
      straightforward or as homogenising as they first appear. The present study
      extends these insights by demonstrating how even standards designed simply to
      collect data can produce extensive and unanticipated effects in medical fields as
      their uses evolve across actors and contexts. We draw on an embedded case study
      exploring the multifaceted consequences of the use of a practice-driven voluntary
      documentation standard: the Swedish rheumatology quality registry from 1995-2014.
      Data collection included document analysis; 100 interviews with specialists,
      patients and stakeholders in the field; fieldwork; and observations of physician
      patient encounters. Our findings show that the scope and influence of the
      registry increased over time, and that this standard and its evolution
      contributed to changes in rheumatologist clinical practice, research practice,
      and governmental practice. These findings suggest that even initially 'weak',
      voluntary forms of standardisation can generate far-reaching and unpredictable
      consequences for the performance and delivery of care as well as for the
      development of a medical field. Future work about how standards can contribute
      both to uniformity and diversity is warranted.

PMID- 27882570
TI  - Ultrastructural and biomolecular detection of Rickettsiales-like organisms in
      tissues of rainbow trout with Red Mark Syndrome.
AB  - Red mark syndrome (RMS) and US strawberry disease (US SD) are skin disorders
      affecting rainbow trout farmed in Europe and USA. The disease etiology has not
      yet been established. In spite of specific investigations, identifying Rickettsia
      like organism (RLO)- and Midichloria-like organism (MLO)-related DNA in affected
      individuals, these pathogens have never been observed. We performed histological,
      ultrastructural and biomolecular analysis on skin and spleen samples of trout
      with RMS. Examination by TEM revealed the presence of intracytoplasmic
      microorganisms resembling Rickettsiales within macrophages, fibroblasts and
      erythrocytes. The microorganisms were oval or short rod shaped (400-800 nm in
      length and 100-200 nm in width) and often showed a cell wall similar to Gram
      negative bacteria. PCR analysis for Rickettsiales supported these findings: 53%
      of affected trout were positive by both PCR and TEM The primers RiFCfw-RiFCrev
      were used to anneal both the RLO 16S DNA sequence and the MLO 16S DNA sequence.
      For this reason, and in agreement with previous studies confirming the presence
      of Rickettsiales-related DNA in trout with RMS, we assume that TEM detected
      microorganisms morphologically consistent with bacteria belonging to
      Rickettsiales order and could be considered as possible causative agents of RMS.

PMID- 27882569
TI  - Selective reduction in the expression of UGTs and SULTs, a novel mechanism by
      which piperine enhances the bioavailability of curcumin in rat.
AB  - Curcumin (CUR) is known to exert numerous health-promoting effects in
      pharmacological studies, but its low bioavailability hinders the development of
      curcumin as a feasible therapeutic agent. Piperine (PIP) has been reported to
      enhance the bioavailability of curcumin, but the underlying mechanism remains
      poorly understood. In an attempt to find the mechanism by which piperine enhances
      the bioavailability of curcumin, the dosage ratio (CUR: PIP) and pre-treatment
      with piperine were hypothesized as key factors for improving the bioavailability
      in this combination. Therefore, combining curcumin with piperine at various dose
      ratios (1:1 to 100:1) and pre-dosing with piperine (0.5-8 h prior to curcumin)
      were designed to investigate their contributions to the pharmacokinetic
      parameters of curcumin in rats and their effects on the expression of UGT and
      SULT isoforms. It was shown that the Cmax and AUC0-t of curcumin were slightly
      increased by 1.29 and 1.67 fold at a ratio of 20:1, while curcumin exposure was
      enhanced significantly in all the piperine pre-treated rats (0.5-8 h), peaking at
      6 h (a 6.09-fold and 5.97-fold increase in Cmax and AUC0-t , p < 0.01),
      regardless of the unchanged t1/2 and Tmax . Also observed was a time-dependent
      inhibition of the hepatic expression of UGT1A6, 1A8, SULT1A1, 1A3, and the
      colonic expression of UGT1A6 that occurred within 6 h of piperine pre-treatment
      but was reversed at 8 h, which correlated with the changes in curcumin exposure.
      Similarly, the inhibitory effect of piperine on most of the UGTs and SULTs are
      time-dependent in Caco-2 and HepG2 cells. It is concluded that piperine pre
      treatment time-dependently improves the bioavailability of curcumin through the
      reversible and selective inhibition of UGTs and SULTs. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27882571
TI  - A note on statistical repeatability and study design for high-throughput assays.
AB  - Characterizing the technical precision of measurements is a necessary stage in
      the planning of experiments and in the formal sample size calculation for optimal
      design. Instruments that measure multiple analytes simultaneously, such as in
      high-throughput assays arising in biomedical research, pose particular challenges
      from a statistical perspective. The current most popular method for assessing
      precision of high-throughput assays is by scatterplotting data from technical
      replicates. Here, we question the statistical rationale of this approach from
      both an empirical and theoretical perspective, illustrating our discussion using
      four example data sets from different genomic platforms. We demonstrate that such
      scatterplots convey little statistical information of relevance and are
      potentially highly misleading. We present an alternative framework for assessing
      the precision of high-throughput assays and planning biomedical experiments. Our
      methods are based on repeatability-a long-established statistical quantity also
      known as the intraclass correlation coefficient. We provide guidance and software
      for estimation and visualization of repeatability of high-throughput assays, and
      for its incorporation into study design. (c) 2016 The Authors. Statistics in
      Medicine Published by John Wiley & Sons Ltd.

PMID- 27882572
TI  - A paired comparison of thawed and liquid plasma.
AB  - BACKGROUND: To make plasma readily available to treat major hemorrhage, some
      centers are internationally using either thawed plasma (TP) or "never-frozen"
      liquid plasma (LP). Despite the routine use of both, there are limited data
      comparing the two. The hemostatic properties of LP were evaluated and compared to
      TP in a paired study. STUDY DESIGN AND METHODS: Two ABO-matched plasma units were
      pooled and split to produce 1 unit for LP and 1 unit for TP. Samples of TP and
      LP, stored at 2 to 6 degrees C, were tested for a range of coagulation factors,
      thrombin generation, and rotational thromboelastometry. An additional 119 units
      of LP were collected and analyzed for markers of contact activation (S-2302
      cleavage) and cellular content. RESULTS: LP and TP were compared, up to 7 days of
      storage, with results showing no difference in the rate of change over time for
      any variable measured. When compared to Day 5, LP on Day 7 showed no difference
      for any factors measured; however, on Day 11 Factor (F)II, FV, FVII, and protein
      S (activity) were lower. Analysis of 119 LP units showed that 26 of 119 (22%)
      exhibited cold-induced contact activation by Day 28. CONCLUSION: LP and TP were
      comparable in terms of hemostatic variables up to 7 days of storage. Decreasing
      coagulation factor activity along with an increased activation risk during
      storage of LP needs to be balanced against availability to supply and clinical
      need when considering using LP with more than 7 days of storage.

PMID- 27882574
TI  - Inter- and intra-operator variability in the analysis of packed cell volume.
AB  - OBJECTIVES: To identify whether inter- and intra-operator variability occurs in
      the measurement of canine packed cell volume and, if so, at which stage these
      errors occur. MATERIALS AND METHODS: Undergraduate veterinary students and
      veterinary surgeons were recruited to measure the packed cell volumes of three
      samples in duplicate. Measurements from each sample were confirmed by one author,
      and it was then ascertained whether the error was made in the capillary
      preparation or reading. RESULTS: Data were obtained from 44 students and 11 vets.
      A total of 25% of students made errors associated with inadequate mixing; 23%
      students and 9% of vets made errors consistent with incorrect reading. There was
      also less intra-operator variation in values within the vet group (0.027 from the
      mean) in comparison to the student group (-0.21 from the mean). A total of 68.2%
      of students and 91% of vets filled the capillary tubes outwith World Health
      Organisation standards of two-thirds to three-quarters full. CLINICAL
      SIGNIFICANCE: Packed cell volume measurement is extremely useful when measuring
      erythroid mass, but it is crucial that the results upon which decisions are made
      are accurate and precise in order to manage these cases appropriately. Operator
      variation is a significant factor and must be addressed by proper training and
      following standard operating procedures.

PMID- 27882575
TI  - Influence of the dipolar interactions on the relative stability in spin crossover
      systems.
AB  - Molecules exhibiting a spin-crossover transition have been proposed for a number
      of applications such as molecular switches, spintronic tunable interfaces, and
      single molecule gates. Both the rational design of new spin-crossover systems and
      the improvement of the properties of the already existing ones require a
      theoretical understanding of the relative energy of the high (HS) and low spin
      state (LS) molecules in the solid-state. This has proved to be very challenging
      so far. Here, we shed some light on the importance of considering the symmetry
      and the geometry of the crystallographic cell to correctly evaluate the influence
      of the dipolar interactions on the relative energies of the molecular complex in
      both different spin states. Moreover, in the case of Fe(SCN)2 (phen)2 dipolar
      interactions are found to play an important role for the stabilization of the LS
      complex. (c) 2016 Wiley Periodicals, Inc.

PMID- 27882573
TI  - Effects of nurse work environment on job dissatisfaction, burnout, intention to
      leave.
AB  - BACKGROUND: The nursing shortage is a critical issue in many countries. High
      turnover rates among nurses is contributing to the shortage, and job
      dissatisfaction, intention to leave, and burnout have been identified as some of
      the predictors of nurse turnover. A well-established body of evidence
      demonstrates that the work environment for nurses influences nurse job
      dissatisfaction, intention to leave, and burnout, but there never has been a
      study undertaken in Thailand to investigate this relationship. OBJECTIVES: To
      investigate how work environment affects job dissatisfaction, burnout, and
      intention to leave among nurses in Thailand. METHODS: The study used a cross
      sectional survey to collect data from 1351 nurses working in 43 inpatient units
      in five university hospitals across Thailand. The participants completed the
      Practice Environment Scale of the Nursing Work Index, the Maslach Burnout
      Inventory, and measures of job dissatisfaction and intention to leave. Logistical
      regression models assessed the association between work environment and nurse
      reported job dissatisfaction, burnout, and intent to leave. RESULTS: Nurses
      working in university hospitals with better work environments had significantly
      less job dissatisfaction, intention to leave, and burnout. CONCLUSION: The nurse
      work environment is a significant feature contributing to nurse retention in Thai
      university hospitals. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Improving the
      work environment for nurses may lead to lower levels of job dissatisfaction,
      intention to leave, and burnout. Focusing on these nurse outcomes can be used as
      a strategy to retain nurses in the healthcare system. Addressing the challenges
      of poor work environments requires coordinated action from policymakers and
      health managers.

PMID- 27882576
TI  - Looking and listening for learning in arts- and humanities-based creations.
AB  - CONTEXT: The arts and humanities are gradually gaining a foothold in health
      professions education as a means of supporting the development of future
      clinicians who are compassionate, critical and reflexive thinkers, while also
      strengthening clinical skills and practices that emphasise patient-centredness,
      collaboration and interprofessional practices. Assignments that tap into trainee
      creativity are increasingly used both to prepare learners for the demands of
      clinical work and to understand the personal and professional challenges learners
      face in these contexts. Health professions educators need methods for
      interpreting these creations in order to understand each learner's expressions.
      This paper describes two theoretical frameworks that can be used to understand
      trainees' unique learning experiences as they are expressed in arts- and
      humanities-based creations. METHODS: The authors introduce the philosophical
      underpinnings and interpretation procedures of two theoretical frameworks that
      enable educators to 'hear' and 'see' the multilayered expressions embedded within
      arts- and humanities-based student creations: Gilligan's Listening Guide and
      Kress and van Leeuwen's approach to visual rhetoric. To illustrate how these
      frameworks can be used, the authors apply them to two creative summaries that
      learners made as part of a humanities-informed, interprofessional education
      intervention that took place in a non-acute-care teaching hospital. The
      interpretations of two creative summaries, a poem and a pair of paintings,
      highlight how applying these theoretical frameworks can offer important insights
      into learners' experiences. CONCLUSIONS: This cross-cutting edge paper describes
      how the Listening Guide and visual rhetoric can help health professions educators
      listen to and read the arts- and humanities-based creative expressions made by
      learners. Insights gained from these interpretations can advance the
      understanding of students' personal experiences in different learning
      environments and can inform curriculum development.

PMID- 27882577
TI  - Sesamoid bones in tuatara (Sphenodon punctatus) investigated with X-ray
      microtomography, and implications for sesamoid evolution in Lepidosauria.
AB  - Sesamoids bones are small intra-tendinous (or ligamentous) ossifications found
      near joints and are often variable between individuals. Related bones, lunulae,
      are found within the menisci of certain joints. Several studies have described
      sesamoids and lunulae in lizards and their close relatives (Squamata) as
      potentially useful characters in phylogenetic analysis, but their status in the
      extant outgroup to Squamata, tuatara (Sphenodon), remains unclear. Sphenodon is
      the only living rhynchocephalian, but museum specimens are valuable and difficult
      to replace. Here, we use non-destructive X-ray microtomography to investigate the
      distribution of sesamoids and lunulae in 19 Sphenodon specimens and trace the
      evolution of these bones in Lepidosauria (Rhynchocephalia + Squamata). We find
      adult Sphenodon to possess a sesamoid and lunula complement different from any
      known squamate, but also some variation within Sphenodon specimens. The
      penultimate phalangeal sesamoids and tibial lunula appear to mineralize prior to
      skeletal maturity, followed by mineralization of a sesamoid between metatarsal I
      and the astragalocalcaneum (MTI-AC), the palmar sesamoids, and tibiofemoral
      lunulae around attainment of skeletal maturity. The tibial patella, ulnar, and
      plantar sesamoids mineralize late in maturity or variably. Ancestral state
      reconstruction indicates that the ulnar patella and tibiofemoral lunulae are
      synapomophies of Squamata, and the palmar sesamoid, tibial patella, tibial
      lunula, and MTI-AC may be synapomorphies of Lepidosauria. J. Morphol. 278:62-72,
      2017. (c)(c) 2016 Wiley Periodicals,Inc.

PMID- 27882578
TI  - Creative art and medical student development: a qualitative study.
AB  - OBJECTIVES: Although many medical schools include arts-based activities in their
      curricula, empirical evidence is lacking regarding how the creation of art might
      impact medical students and their professional development. We used a qualitative
      research design in order to understand this process. METHODS: We conducted and
      analysed interviews with 16 medical students who had created and presented
      original artwork in the context of a required narrative-based undergraduate
      medical education programme. Teams of students collaborated to create
      interpretive projects based on common themes arising from conversations with
      individuals with chronic illness and their families. Open-ended questions were
      utilised to explore the conceptualisation and presentation of the projects, the
      dynamics of teamwork and the meaning(s) they might have for the students'
      professional development. We identified themes using repeated contextual reading
      of the transcripts, which also enhanced accuracy of the interpretations and
      ensured saturation of themes. RESULTS: Several major themes and sub-themes were
      identified. The creation of art led to a sense of personal growth and
      development, including reflection on past life experiences, self-discovery and an
      awareness of art as a creative outlet. Students also reported an enhanced sense
      of community and the development of skills in collaboration. Lastly, students
      reflected on the human dimensions of illness and medical care and identified an
      enhanced awareness of the experience of those with illness. CONCLUSIONS: A
      programme involving the creation of art based on stories of illness encouraged
      students' explorations of conceptions of the self, family and society, as well as
      illness and medical care, while enhancing the development of a collaborative and
      patient-centred worldview. Creative art can be a novel educational tool to
      promote a reflective, humanistic medical practice.

PMID- 27882579
TI  - Learner : preceptor ratios for practice-based learning across health disciplines:
      a systematic review.
AB  - CONTEXT: Practice-based learning is a cornerstone of developing clinical and
      professional competence in health disciplines. Practice-based learning systems
      have many interacting components, but a key facet is the number of learners per
      preceptor. Different learner : preceptor ratios may have unique benefits and pose
      unique challenges for participants. This is the first comprehensive systematic
      review of the topic. Our research questions were: What are the benefits and
      challenges of each learner : preceptor ratio in practice-based learning from the
      perspectives of the learners, preceptors, patients and stakeholder organisations
      (i.e. the placing and health care delivery organisations)? Are any ratios
      superior to others with respect to these characteristics and perspectives?
      METHODS: Qualitative systematic review of published English-language literature
      since literature database inception, including multiple health disciplines.
      RESULTS: Seventy-three articles were included in this review. Eight learner :
      preceptor ratio arrangements were identified involving nursing, physiotherapy,
      occupational therapy, pharmacy, dietetics, speech and language therapy, and
      medicine. Each arrangement offers unique benefits and challenges from the
      perspectives of learners, preceptors, programmes and health care delivery
      organisations. Patient perspectives were absent. Despite important advantages of
      each ratio for learners, preceptors and organisations, some of which may be
      profession specific, the 2 : 1 and 2+ : 2+ learner : preceptor ratios appear to
      be most likely to successfully balance the needs of all stakeholders.
      CONCLUSIONS: Regardless of the learner : preceptor ratio chosen for its expected
      benefits, our results illuminate challenges that can be anticipated and managed.
      Patient perspectives should be incorporated into future studies of learner :
      preceptor ratios.

PMID- 27882580
TI  - When I say ... sociomateriality.

PMID- 27882581
TI  - Achieved good response of S-1 and docetaxel combination chemotherapy in two
      patients with metastatic extramammary Paget's disease.

PMID- 27882582
TI  - Hormonal treatment with transdermal testosterone in patients with male accessory
      gland inflammation (MAGI): Effects on sperm parameters.
AB  - Recently, it has been reported that treatment with testosterone (T) could have
      favourable effects on prostate inflammation; however, the data appear
      inconsistent. The main evidences concern experimental studies, and there is lower
      information obtainable from clinical studies. This study was conducted on
      patients with diagnosis of male accessory gland infection (MAGI) and a
      concomitant hormonal condition of acquired hypergonadotropic hypogonadism and has
      evaluated the effects on sperm parameters of the administration of a transdermal
      formulation of T gel for 3 months. The treated patients showed a significantly
      increased percentage of spermatozoa with normal form and progressive motility (p
      < .05 vs baseline), a significant reduction of CD45pos leucocytes in the semen (p
      < .05 vs baseline) and finally a significant increase of the seminal
      concentrations of zinc, fructose and alpha-glucosidase (p < .05 vs baseline)
      identified as key parameters associated to secretory function of the male
      accessory glands. The results of this study suggest the use of transdermal T in
      hypogonadal patients with MAGI for favourable effects on sperm parameters.

PMID- 27882584
TI  - When I say ... chief complaint.

PMID- 27882583
TI  - How clinical medical students perceive others to influence their self-regulated
      learning.
AB  - OBJECTIVES: Undergraduate medical students are prone to struggle with learning in
      clinical environments. One of the reasons may be that they are expected to self
      regulate their learning, which often turns out to be difficult. Students' self
      regulated learning is an interactive process between person and context, making a
      supportive context imperative. From a socio-cultural perspective, learning takes
      place in social practice, and therefore teachers and other hospital staff present
      are vital for students' self-regulated learning in a given context. Therefore, in
      this study we were interested in how others in a clinical environment influence
      clinical students' self-regulated learning. METHODS: We conducted a qualitative
      study borrowing methods from grounded theory methodology, using semi-structured
      interviews facilitated by the visual Pictor technique. Fourteen medical students
      were purposively sampled based on age, gender, experience and current clerkship
      to ensure maximum variety in the data. The interviews were transcribed verbatim
      and were, together with the Pictor charts, analysed iteratively, using constant
      comparison and open, axial and interpretive coding. RESULTS: Others could
      influence students' self-regulated learning through role clarification, goal
      setting, learning opportunities, self-reflection and coping with emotions. We
      found large differences in students' self-regulated learning and their
      perceptions of the roles of peers, supervisors and other hospital staff. Novice
      students require others, mainly residents and peers, to actively help them to
      navigate and understand their new learning environment. Experienced students who
      feel settled in a clinical environment are less susceptible to the influence of
      others and are better able to use others to their advantage. CONCLUSIONS:
      Undergraduate medical students' self-regulated learning requires context-specific
      support. This is especially important for more novice students learning in a
      clinical environment. Their learning is influenced most heavily by peers and
      residents. Supporting novice students' self-regulated learning may be improved by
      better equipping residents and peers for this role.

PMID- 27882585
TI  - Clinicopathological significance of a solid component in papillary thyroid
      carcinoma.
AB  - AIMS: Solid variant of papillary thyroid carcinoma (SVPTC) is characterized by a
      solid component (SC) involving more than 50% of the tumour with the preservation
      of the classical cytological features of papillary thyroid carcinoma (PTC).
      However, the clinical significance of SC in PTC has been rarely examined. Herein,
      we investigated retrospectively the clinicopathological features of PTC with
      various degrees (10-85%) of SC (PTCSC). METHODS AND RESULTS: Patients with PTCSC
      (n = 27) were stratified into SC-major (SC > 50% of the tumour) and SC-minor (SC
      < 49%) groups. The clinicopathological parameters were compared to the well
      differentiated PTC (WPTC) group (n = 47). Both SC-minor (n = 18) and SC-major (n
      = 9) groups had increased incidence of a large-sized tumour, extracapsular
      extension and a high recurrence rate, compared to WPTC. Disease-free survival
      (DFS) of both SC-minor and SC-major was shorter than that of WPTC (P = 0.035 and
      P = 0.016, respectively). Overall survival was similar among all the groups.
      Univariate analysis revealed that SC was associated significantly with a
      recurrence rate (P = 0.018). Using multivariate analysis, SC appeared to be
      associated with a recurrence rate with borderline significance (P = 0.055).
      CONCLUSIONS: Our findings indicate that the presence of SC in PTC, regardless of
      the proportion, is associated with adverse clinical parameters and a shorter DFS.

PMID- 27882587
TI  - "Pushing the Button While Pushing the Argument": Motor Priming of Abstract Action
      Language.
AB  - In a behavioral study we analyzed the influence of visual action primes on
      abstract action sentence processing. We thereby aimed at investigating mental
      motor involvement during processes of meaning constitution of action verbs in
      abstract contexts. In the first experiment, participants executed either
      congruous or incongruous movements parallel to a video prime. In the second
      experiment, we added a no-movement condition. After the execution of the
      movement, participants rendered a sensibility judgment on action sentence
      targets. It was expected that congruous movements would facilitate both concrete
      and abstract action sentence comprehension in comparison to the incongruous and
      the no-movement condition. Results in Experiment 1 showed a concreteness effect
      but no effect of motor priming. Experiment 2 revealed a concreteness effect as
      well as an interaction effect of the sentence and the movement condition. The
      findings indicate an involvement of motor processes in abstract action language
      processing on a behavioral level.

PMID- 27882588
TI  - Clinical and epidemiological analysis in 149 cases of rhododendrol-induced
      leukoderma.
AB  - Rhododendrol-induced leukoderma is an acquired depigmentation that develops
      mainly at the contact site after repeated use of skin-whitening cosmetics
      containing rhododendrol. In most cases, cessation of further depigmentation or
      occurrence of repigmentation is observed after discontinuing the use of
      cosmetics. However, some patients develop vitiligo vulgaris through the spread of
      depigmentation into the non-exposed areas. Our study aims to investigate the
      patient-specific factors that may affect the extent of depigmentation or
      repigmentation, as well as development of vitiligo vulgaris. The degree of
      depigmentation of the face, neck and hands where exposed to rhododendrol was
      scored using photographs over time. The relationships between depigmentation
      score at first visit/improvement rate of depigmentation score and patient
      demographics were evaluated and three important clinical observations were made.
      First, repigmentation of the face was superior compared with that of the hands
      and neck, suggesting a possible role for the migration and differentiation of
      melanocyte stem cells from hair follicles, as a mechanism of repigmentation.
      Second, the intensity of rhododendrol exposure did not contribute to differences
      in the severity of depigmentation. This suggested a possibility of underlying
      genetic susceptibility to melanocyte cytotoxicity or immune reaction. Third,
      depigmentation score at first visit and past history of atopic dermatitis were
      significantly high in patients who developed vitiligo vulgaris. This suggested
      that severe chemical damage of melanocytes by rhododendrol leads to a higher risk
      of developing vitiligo vulgaris through the possible involvement of an immune
      reaction. These clinical observations may help to further understand the
      pathogenesis of rhododendrol-induced leukoderma.

PMID- 27882590
TI  - Non-pigmented basal cell carcinoma occurring within a widespread vitiliginous
      lesion.

PMID- 27882591
TI  - More than a coincidence? Cholesterol crystal embolization in the unaffected
      abdominal skin.

PMID- 27882589
TI  - Attenuation of the cyproterone acetate-induced testicular hypofunction by a novel
      nutraceutical lycopene: a genomic approach.
AB  - This study was designed to explore the cyproterone acetate (CPA)-induced
      andrological hypofunction and its correction by oral administration of lycopene.
      In this concern, spermatogenic, biochemical, histological and genomic profiles
      were studied. Cyproterone acetate administration for 1 month helped to develop
      infertile model rats. A significant recovery was noted in sperm motility, sperm
      count, sperm viability, hypo-osmotic swelling tail-coiled spermatozoa; activities
      of testicular ?5 , 3beta-hydroxysteroid dehydrogenase (HSD), 17beta-HSD, catalase
      (CAT) and superoxide dismutase (SOD); and levels of conjugated diene (CD),
      malondialdehyde (MDA), testicular cholesterol and serum testosterone after the
      administration of lycopene at 1.5 mg/0.5 ml Tween-80/100 g body weight/day for
      last 1 month to infertile model rats. Simultaneously, qRT-PCR study of Bax, Bcl
      2, caspase-3, ?5 , 3beta-HSD and 17beta-HSD genes in testicular tissue showed a
      significant rectification towards the control in CPA-pre-treated cum CPA-lycopene
      cotreated rats. Side-by-side histological and histometric studies showed a
      significant correction in qualitative analysis of spermatogenesis and
      seminiferous tubular diameter (STD) in CPA-pre-treated cum CPA-lycopene-cotreated
      rats. Lycopene showed outstanding efficacy in the management of CPA-induced
      testicular hypofunction with special reference to correction in oxidative stress
      induced testicular apoptosis at genomic level.

PMID- 27882592
TI  - Ureterorenoscopy with stenting and its effect on male sexual function: A
      controlled randomised prospective study.
AB  - Seventy-two male patients, who were included in this study, underwent
      ureteroscopic stone surgery (study group). Forty-two healthy males were enrolled
      as control group. Changes in sexual function were evaluated using International
      Index of Erectile Function questionnaire in pre-operative, first and third
      postoperative terms. Overall satisfaction in relation to the age, operation time,
      presence of stents, body mass index, educational status, previous operations,
      International Index of Erectile Function score, International Prostate Symptom
      Score, Quality of Life, income status, Male Sexual Health Questionnaire, stone
      free rates and Beck's depression scale were evaluated. Erectile and ejaculatory
      functions, quality of life and lower urinary tract symptoms were negatively
      affected due to ureteroscopic stone surgery, while educational status,
      psychogenic aspect and income status remained stable. In conclusion,
      ureteroscopic stone surgery with JJ catheterisation seems to have a progressively
      decreasing negative effect on male sexual function and whenever possible,
      stenting should be avoided. If JJ stenting is necessary, patients should be
      informed that they may experience sexual dysfunction at least for 3 months and if
      stenting proves necessary the indwelling should be kept as short as possible.

PMID- 27882586
TI  - Efficacy and safety of dose escalation of infliximab therapy in Japanese patients
      with psoriasis: Results of the SPREAD study.
AB  - Although infliximab is approved for psoriasis, its efficacy is reduced over time
      in some patients. The aim of this phase III trial is to evaluate efficacy and
      safety of infliximab dose escalation in Japanese psoriasis patients with loss of
      efficacy to standard-dose therapy. Patients with plaque psoriasis, psoriatic
      arthritis, pustular psoriasis or psoriatic erythroderma who showed loss of
      efficacy to standard-dose therapy received infliximab dose escalation (10 mg/kg
      every 8 weeks) from weeks 0 to 32. Loss of efficacy was defined as not
      maintaining 50% reduction in the Psoriasis Area and Severity Index (PASI 50)
      after achieving PASI 75. Efficacy and safety were evaluated up to week 40. Fifty
      one patients received dose escalation and 43 completed the study. PASI 75 and
      median improvement rate of PASI score at week 40 were 44% and 70.0%,
      respectively, showing efficacy in skin symptoms. Efficacies in quality of life,
      nail psoriasis and joint pain were also obtained. Median serum infliximab level
      increased from less than 0.1 to 1.1 MUg/mL from weeks 0 to 40, showing positive
      correlation between efficacy and serum infliximab level at week 40. Favorable
      efficacy was observed in patients with detectable serum infliximab levels (>=0.1
      MUg/mL) at baseline. Incidences of adverse events, serious adverse events,
      serious infections and serious infusion reactions were 92%, 10%, 4% and 0%,
      respectively. No marked difference was observed in both efficacy and safety among
      psoriasis types. No new safety concerns were observed. Infliximab dose escalation
      was effective and well-tolerated in psoriasis patients with loss of efficacy to
      standard-dose therapy, suggesting that dose escalation may be a useful
      therapeutic option for these patients.

PMID- 27882593
TI  - Can colleagues', patients' and supervisors' assessments predict successful
      completion of postgraduate medical training?
AB  - BACKGROUND: Workplace-based assessments (WPBAs) are widely used in postgraduate
      training programmes internationally. WPBAs can function as both an assessment and
      an educational tool. Although some WPBAs are a mandatory requirement of approved
      curricula (as in the UK), little previous research has explored the extent to
      which such assessments are associated with adverse outcomes in postgraduate
      training. The present study examines whether the assessment element of
      Multisource Feedback, Patient Satisfaction Questionnaire and Educational
      Supervisors Review ratings can indicate if a trainee is likely to experience
      difficulty in successfully completing their planned training programme (i.e. fail
      one of their licensing assessments or need additional training time). METHODS:
      Data were collected for trainees undergoing a General Practice specialty training
      placement in Health Education East Midlands (UK). Multivariate analyses were used
      to examine the predictive validity of the WPBAs and the outcome measures (n = 327
      to 329) and t-tests to calculate whether there were significant differences in
      performance between trainees who received low versus high WPBA ratings (t = 4.03
      to 10.27, p < 0.01). RESULTS: Multisource Feedback, Patient Satisfaction
      Questionnaire and Educational Supervisor's Review ratings were significantly
      correlated with subsequent performance in licensing exams (r = 0.14 to 0.47, p <
      0.01), and in addition explained significant variance in the likelihood of
      requiring additional training time (15.6% to 25.6%, p < 0.01). CONCLUSIONS: Based
      on the findings, we assert that Multisource Feedback, Patient Satisfaction
      Questionnaire and Educational Supervisor's Review ratings have validity for
      predicting performance during training and are thus a useful tool for identifying
      trainees who are more likely to experience difficulty and could benefit from
      early additional support.

PMID- 27882594
TI  - "Cuts in Action": A High-Density EEG Study Investigating the Neural Correlates of
      Different Editing Techniques in Film.
AB  - In spite of their striking differences with real-life perception, films are
      perceived and understood without effort. Cognitive film theory attributes this to
      the system of continuity editing, a system of editing guidelines outlining the
      effect of different cuts and edits on spectators. A major principle in this
      framework is the 180 degrees  rule, a rule recommendation that, to avoid
      spectators' attention to the editing, two edited shots of the same event or
      action should not be filmed from angles differing in a way that expectations of
      spatial continuity are strongly violated. In the present study, we used high
      density EEG to explore the neural underpinnings of this rule. In particular, our
      analysis shows that cuts and edits in general elicit early ERP component
      indicating the registration of syntactic violations as known from language,
      music, and action processing. However, continuity edits and cuts-across the line
      differ from each other regarding later components likely to be indicating the
      differences in spatial remapping as well as in the degree of conscious awareness
      of one's own perception. Interestingly, a time-frequency analysis of the
      occipital alpha rhythm did not support the hypothesis that such differences in
      processing routes are mainly linked to visual attention. On the contrary, our
      study found specific modulations of the central mu rhythm ERD as an indicator of
      sensorimotor activity, suggesting that sensorimotor networks might play an
      important role. We think that these findings shed new light on current
      discussions about the role of attention and embodied perception in film
      perception and should be considered when explaining spectators' different
      experience of different kinds of cuts.

PMID- 27882595
TI  - Children's Representation and Imitation of Events: How Goal Organization
      Influences 3-Year-Old Children's Memory for Action Sequences.
AB  - Children's imitation of adults plays a prominent role in human cognitive
      development. However, few studies have investigated how children represent the
      complex structure of observed actions which underlies their imitation. We
      integrate theories of action segmentation, memory, and imitation to investigate
      whether children's event representation is organized according to veridical
      serial order or a higher level goal structure. Children were randomly assigned to
      learn novel event sequences either through interactive hands-on experience (Study
      1) or via storybook (Study 2). Results demonstrate that children's representation
      of observed actions is organized according to higher level goals, even at the
      cost of representing the veridical temporal ordering of the sequence. We argue
      that prioritizing goal structure enhances event memory, and that this mental
      organization is a key mechanism of social-cognitive development in real-world,
      dynamic environments. It supports cultural learning and imitation in ecologically
      valid settings when social agents are multitasking and not demonstrating one
      isolated goal at a time.

PMID- 27882596
TI  - Core Intuitions About Persons Coexist and Interfere With Acquired Christian
      Beliefs About God.
AB  - This study tested the hypothesis that in the minds of adult religious adherents,
      acquired beliefs about the extraordinary characteristics of God coexist with,
      rather than replace, an initial representation of God formed by co-option of the
      evolved person concept. In three experiments, Christian religious adherents were
      asked to evaluate a series of statements for which core intuitions about persons
      and acquired Christian beliefs about God were consistent (i.e., true according to
      both [e.g., "God has beliefs that are true"] or false according to both [e.g.,
      "All beliefs God has are false"]) or inconsistent (i.e., true on intuition but
      false theologically [e.g., "God has beliefs that are false"] or false on
      intuition but true theologically [e.g., "All beliefs God has are true"]).
      Participants were less accurate and slower to respond to inconsistent versus
      consistent statements, suggesting that the core intuitions both coexisted
      alongside and interfered with the acquired beliefs (Experiments 1 and 2). In
      Experiment 2 when responding under time pressure participants were
      disproportionately more likely to make errors on inconsistent versus consistent
      statements than when responding with no time pressure, suggesting that the
      resolution of interference requires cognitive resources the functioning of which
      decreases under cognitive load. In Experiment 3 a plausible alternative
      interpretation of these findings was ruled out by demonstrating that the response
      accuracy and time differences on consistent versus inconsistent statements occur
      for God-a supernatural religious entity-but not for a natural religious entity (a
      priest).

PMID- 27882598
TI  - Kaposi's varicelliform eruption presenting with extensive skin lesions and
      sepsis.

PMID- 27882597
TI  - Morphological analyses in fragility of pili torti with Bjornstad syndrome.
AB  - Pili torti is an extremely rare hair phenotype characterized by short length of
      hairs with hair shafts being easily broken. However, the mechanism of fragility
      in pili torti is unclear. In this study, we examined the underlying morphological
      features responsible for pili torti formation using transmission electron
      microscopy (TEM). We used pili torti samples from a patient with Bjornstad
      syndrome and normal hairs from a healthy subject as a comparison. The macroscopic
      morphological features of the samples agreed with the results of a previous study
      showing that pili torti is twisted, flattened, thin and with partial
      trichorrhexis. Young's modulus of the samples was lower than that of normal
      hairs. Because the cross-sectional area of the pili torti samples was also
      smaller than that of normal hairs, it was clarified that the tensile strength of
      pili torti is 2.1-times lower than that of normal hair. Assessment of
      morphological features by TEM showed that the cuticle layers of the samples had
      wavy shapes with different thicknesses. Additionally, the cortex in the samples
      showed loose keratin intermediate filaments (IF). Our results suggested that
      these abnormalities in pili torti had already occurred below the infundibulum.
      Thus, the weakness of pili torti in tensile strength is thought to result from
      loose IF because of dysformation of disulfide bonds.

PMID- 27882599
TI  - 46,XX males: a case series based on clinical and genetics evaluation.
AB  - 46,XX male sex reversal syndrome is one of the rarest sex chromosomal
      aberrations. The presence of SRY gene on one of the X chromosomes is the most
      frequent cause of this syndrome. Based on Y chromosome profile, there are SRY
      positive and SRY-negative forms. The purpose of our study was to report first
      case series of Iranian patients and describe the different clinical appearances
      based on their genetic component. From the 8,114 azoospermic and severe
      oligozoospermic patients referred to Royan institute, we diagnosed 57 cases as
      sex reversal patients. Based on the endocrinological history, we performed
      karyotyping, SRY and AZF microdeletion screening. Patients had a female
      karyotype. According to available hormonal reports of 37 patients, 16 cases had
      low levels of testosterone (43.2%). On the other hand, 15 males were SRY positive
      (90.2%), while they lacked the spermatogenic factors encoding genes on Yq.
      Commencing the testicular differentiation in males, the SRY gene is considered to
      be very important in this process. Due to homogeneous results of karyotyping and
      AZF deletion, there are both positive and negative SRY cases that show similar
      sex reversal phenotypes. Evidences show that there could be diverse phenotypic
      differences that could be raised from various reasons.

PMID- 27882601
TI  - Case of pigmented epithelioid melanocytoma affecting the thumbnail.

PMID- 27882600
TI  - Muscular fitness and metabolic and inflammatory biomarkers in adolescents:
      Results from LabMed Physical Activity Study.
AB  - This study aimed to evaluate the associations between muscular fitness and
      inflammatory biomarkers and to investigate the relationship between muscular
      fitness and selected clustered inflammatory biomarkers in adolescents. This is a
      cross-sectional analysis with 529 adolescents (267 girls) aged 12-18 years.
      Handgrip strength and standing long jump tests assessed MF. Continuous scores of
      clustered inflammatory biomarkers (sum of Z-scores of C-reactive protein [CRP],
      C3, C4, fibrinogen, and leptin); metabolic risk factor (MRF) score (sum of Z
      scores of SBP, triglycerides, ratio total cholesterol [TC]/HDL, HOMA-IR, and
      waist circumference [WC]) were computed. Regression analyses showed an inverse
      association between muscular fitness score (beta=-.204; P<.021) and clustered
      score of inflammatory biomarkers, adjusted for age, sex, pubertal stage,
      socioeconomic status, adherence to the Mediterranean diet, cardiorespiratory
      fitness (CRF), MRF score, and body fat. Analysis of covariance showed that
      adolescents with an adverse inflammatory profile with low levels of muscular
      fitness exhibit the poorest MRF score (F3,525 =6.461; P<.001), adjusted for age,
      sex, pubertal stage, socioeconomic status, adherence to the Mediterranean diet,
      CRF, and body fatness. The inflammatory state seems to explain a significant part
      of the highest MRF score and in adolescents with high inflammatory status and low
      muscular strength.

PMID- 27882603
TI  - Establishment and characterization of a cell population derived from a
      dentigerous cyst.
AB  - BACKGROUND: Dentigerous cyst (DC) occurs in approximately 20% of jaw cysts, being
      the second major common odontogenic cyst, after radicular cyst. This oral lesion
      has the ability to destroy maxillary bones and could be the origin of several
      odontogenic tumors. However, molecules implicated in its pathogenesis as well as
      those involved in its neoplastic transformation remain unknown. Here, we
      established a cell population derived from a DC as an in vitro model for the
      study of this oral lesion. METHODS: Cell culture was performed from a DC from a
      44-year-old male. Cells were cultured at 37 degrees C in DMEM/F12 medium
      containing 10% fetal bovine serum. Expression of epithelial markers was analyzed
      by Western blot and immunofluorescence. Ultrastructural characterization was
      carried out by transmission electron microscopy. Conditioned media were obtained
      and characterized by zymography and Western blot. RESULTS: Cells showed spindle
      shaped morphology, but they express epithelial markers, such as cytokeratins and
      the odontogenic ameloblast-associated protein. The ultrastructural analysis
      showed well-formed desmosomes present in adhering contiguous cells, confirming
      the epithelial lineage of this cell population. Cells also contain several
      vesicles adjacent to plasma membrane, suggesting an active secretion. Indeed, the
      analysis of the conditioned medium revealed the presence of several secreted
      proteins, among them the matrix metalloproteinase-2. CONCLUSIONS: Our work
      provides a useful model to identify the molecular mechanisms involved in the
      pathogenesis of DC.

PMID- 27882602
TI  - The resveratrol derivatives trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene and
      trans-2,4',5-trihydroxystilbene decrease oxidative stress and prolong lifespan in
      Caenorhabditis elegans.
AB  - OBJECTIVES: Resveratrol (trans-3,4',5-trihydroxystilbene (1)) was previously
      shown to extend the lifespan of different model organisms. However, its
      pharmacological efficiency is controversially discussed. Therefore, the
      bioactivity of four newly synthesized stilbenes (trans-3,5-dimethoxy-4-fluoro-4'
      hydroxystilbene (3), trans-4'-hydroxy-3,4,5-trifluorostilbene (4), trans-2,5
      dimethoxy-4'-hydroxystilbene (5), trans-2,4',5-trihydroxystilbene (6)) was
      compared to (1) and pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene (2)) in
      the established model organism Caenorhabditis elegans. METHODS: Trolox equivalent
      antioxidant capacity (TEAC), 2',7'-dichlorofluorescein (DCF), thermotolerance
      assays, C. elegans lifespan analyses. KEY FINDINGS: All compounds exert a strong
      in-vitro radical scavenging activity (6 > 1 > 5 > 2 = 3 = 4), but in vivo, only
      (3) and (6) reduce reactive oxygen species (ROS) accumulation. Furthermore, (3)
      and (6) increased the mobility of aged nematodes and prolonged their mean
      lifespans, while these compounds decreased the thermal stress resistance. Using
      daf-16 (FoxO), skn-1 (Nrf2) and sir-2.1 (sirtuin) loss-of-function mutant
      strains, the in vivo antioxidant effects of compounds (3) and (6) were abolished,
      showing the necessity of these evolutionary highly conserved factors. However,
      short-time treatment with stilbenes (3) and (6) did not modulate the cellular
      localization of the transcription factors DAF-16 and SKN-1. CONCLUSION: In
      contrast to resveratrol, the synthetic stilbene derivatives (3) and (6) increase
      the lifespan of C. elegans, rendering them promising candidates for
      pharmacological anti-ageing purposes.

PMID- 27882604
TI  - The "Dog Bone Technique" A Novel Easy and Safe Catheter Maneuver for Aortic Arch
      and Coarctation Stenting.
AB  - BACKGROUND: Various techniques are described to facilitate stable stent
      implantation in aortic arch stenosis or coarctation. We describe an alternative
      technique, which due to its unique appearance during stent implantation, we have
      named "Dog Bone Technique" (DBT). TECHNIQUE: The stent/balloon assembly is placed
      across the stenosis, the long sheath is retrieved to uncover the distal 20-50% of
      the stent. The balloon is inflated with the pressure inflator just to expand
      slightly the stent. Thereafter the sheath is pulled back and the proximal end is
      uncovered and partially inflated; therewith the assembly takes the typical "dog
      bone" shape before complete inflation and final positioning. Repositioning of the
      stent and control angiography is possible at each time of this procedure.
      RESULTS: Between 1/2010 and 12/2014 we implanted 91 stents in 87 patients (mean
      age 20.2 years). About 71 patients had native or re-coarctation and 16 patients
      had transverse aortic arch stenosis. In 38 patients (44%) a pharmacological
      exercise test with Orciprenaline was performed during implantation resulting in
      high-cardiac output. In none of the patients reduction of cardiac output by
      adenosine or a rapid pacing of the right ventricle was required for stable stent
      implantation. All stents were implanted in the targeted position using this
      single balloon technique. There were no acute or short-term complications
      detected. CONCLUSION: DBT is a safe and feasible technique for aortic stent
      implantation even at high-cardiac output. Other additional techniques for stent
      placement are not necessary to obtain a stable final position in the target
      region.

PMID- 27882605
TI  - Placebo in sports nutrition: a proof-of-principle study involving caffeine
      supplementation.
AB  - We investigated the effects of supplement identification on exercise performance
      with caffeine supplementation. Forty-two trained cyclists (age 37 +/- 8 years,
      body mass [BM] 74.3 +/- 8.4 kg, height 1.76 +/- 0.06 m, maximum oxygen uptake
      50.0 +/- 6.8 mL/kg/min) performed a ~30 min cycling time-trial 1 h following
      either 6 mg/kgBM caffeine (CAF) or placebo (PLA) supplementation and one control
      (CON) session without supplementation. Participants identified which supplement
      they believed they had ingested ("caffeine", "placebo", "don't know") pre- and
      post-exercise. Subsequently, participants were allocated to subgroups for
      analysis according to their identifications. Overall and subgroup analyses were
      performed using mixed-model and magnitude-based inference analyses. Caffeine
      improved performance vs PLA and CON (P <= 0.001). Correct pre- and post-exercise
      identification of caffeine in CAF improved exercise performance (+4.8 and +6.5%)
      vs CON, with slightly greater relative increases than the overall effect of
      caffeine (+4.1%). Performance was not different between PLA and CON within
      subgroups (all P > 0.05), although there was a tendency toward improved
      performance when participants believed they had ingested caffeine post-exercise
      (P = 0.06; 87% likely beneficial). Participants who correctly identified placebo
      in PLA showed possible harmful effects on performance compared to CON. Supplement
      identification appeared to influence exercise outcome and may be a source of bias
      in sports nutrition.

PMID- 27882606
TI  - 50-Fold EQE Improvement up to 6.27% of Solution-Processed All-Inorganic
      Perovskite CsPbBr3 QLEDs via Surface Ligand Density Control.
AB  - Solution-processed CsPbBr3 quantum-dot light-emitting diodes with a 50-fold
      external quantum efficiency improvement (up to 6.27%) are achieved through
      balancing surface passivation and carrier injection via ligand density control
      (treating with hexane/ethyl acetate mixed solvent), which induces the coexistence
      of high levels of ink stability, photoluminescence quantum yields, thin-film
      uniformity, and carrier-injection efficiency.

PMID- 27882607
TI  - Fear of failure, psychological stress, and burnout among adolescent athletes
      competing in high level sport.
AB  - The purpose of this study was to investigate fear of failure in highly
      competitive junior athletes and the association with psychological stress and
      burnout. In total 258 athletes (152 males and 108 females) ranged in age from 15
      to 19 years (M = 17.4 years, SD = 1.08) participated. Athletes competed in
      variety of sports including both team and individual sports. Results showed in a
      variable-oriented approach using regression analyses that one dimension, fear of
      experiencing shame and embarrassment had a statistically significant effect on
      perceived psychological stress and one dimension of burnout, reduced sense of
      accomplishment. However, adopting a person-oriented approach using latent class
      analysis, we found that athletes with high levels of fear failure on all
      dimensions scored high on burnout. We also found another class with high scores
      on burnout. These athletes had high scores on the individual-oriented dimensions
      of fear of failure and low scores on the other oriented fear of failure
      dimensions. The findings indicate that fear of failure is related to burnout and
      psychological stress in athletes and that this association is mainly associated
      with the individual-oriented dimensions of fear of failure.

PMID- 27882608
TI  - About the in vivo quantitation of skin anisotropy.
AB  - BACKGROUND/PURPOSE: Human skin anisotropy is difficult to quantify. The
      Cutiscan(r) , is allegedly, the first biometrical system to provide information
      on the elastic and viscoelastic properties, as well as on anisotropy and
      directionality of the human skin in vivo. Thus, this study aims to contribute to
      characterize this new device and its applicability, and to compare its behavior
      with two other well-known devices-the Cutometer(r) and the Reviscometer(r) .
      METHODS: Measurements were conducted with each device in three different
      anatomical sites (forehead, forearm and leg) of 20 female volunteers engaged
      after informed consent. The participants in the study were aged 19-73 years (mean
      age 37 +/- 18.7 years old), and were divided in two groups (n = 10), based on
      their age - Group I, mean age 22 +/- 1.3 years; Group II, mean age 52 +/- 13.7
      years. RESULTS: All devices were useful tools to explore the anatomical and the
      age dependant changes in biomechanical terms, showing different discriminative
      capacities. Interesting correlations were established between the variables
      provided by the equipment. CONCLUSION: The Cutiscan(r) descriptors delivered
      excellent relationships with those from Cutometer(r) and Reviscometer(r) , while
      providing more detailed information about skin anisotropy through a full 360
      degrees  analysis.

PMID- 27882609
TI  - The Application of a Small-Molecule-Based Ternary Memory Device in Transient
      Thermal-Probing Electronics.
AB  - A small-molecule-based ternary memory device is used in transient thermal-probing
      electronics. The PYAE-based memory device is featured with three electrical
      transition signals ("0," "1," and "2"), while the heated PYAE-based device is
      only characterized by two electrical transition signals ("1" and "2"). The
      organic layer of the used devices can be recovered and reused.

PMID- 27882610
TI  - Guiding Cell Attachment in 3D Microscaffolds Selectively Functionalized with Two
      Distinct Adhesion Proteins.
AB  - The combination of three different photoresists into a single direct laser
      written 3D microscaffold permits functionalization with two bioactive full-length
      proteins. The cell-instructive microscaffolds consist of a passivating framework
      equipped with light activatable constituents featuring distinct protein-binding
      properties. This allows directed cell attachment of epithelial or fibroblast
      cells in 3D.

PMID- 27882612
TI  - Relationship between geometry of the extensor mechanism of the knee and risk of
      anterior cruciate ligament injury.
AB  - The complex inter-segmental forces that are developed across an extended knee by
      body weight and contraction of the quadriceps muscle group transmits an
      anteriorly directed force on the tibia that strain the anterior cruciate ligament
      (ACL). We hypothesized that a relationship exists between geometry of the knees
      extensor mechanism and the risk of sustaining a non-contact ACL injury. Geometry
      of the extensor mechanism was characterized using MRI scans of the knees of 88
      subjects that suffered their first non-contact ACL injury and 88 matched control
      subjects with normal knees that were on the same team. The orientation of the
      patellar tendon axis was measured relative to the femoral flexion-extension axis
      to determine the extensor moment arm (EMA), and relative to tibial long axis to
      measure coronal patellar tendon angle (CPTA) and sagittal patellar tendon angle
      (SPTA). Associations between these parameters and ACL injury risk were tested
      with and without adjustment for flexion and internal rotation position of the
      tibia relative to the femur during MRI data acquisition. After adjustment for
      internal rotation position of the tibia relative to the femur there were no
      associations between EMA, CPTA, and SPTA and risk of suffering an ACL injury.
      However, increased internal rotation position of the tibia relative to the femur
      was significantly associated with increased risk of ACL injury in female athletes
      both in univariate analysis (Odds Ratio = 1.16 per degree of internal rotation of
      the tibia, p = 0.002), as well as after adjustment for EMA, CPTA, and SPTA.: (c)
      2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 35:965-973, 2017.

PMID- 27882611
TI  - Chronic lactate supplementation does not improve blood buffering capacity and
      repeated high-intensity exercise.
AB  - Since there is conflicting data on the buffering and ergogenic properties of
      calcium lactate (CL), we investigated the effect of chronic CL supplementation on
      blood pH, bicarbonate, and high-intensity intermittent exercise performance.
      Sodium bicarbonate (SB) was used as a positive control. Eighteen athletes
      participated in this double-blind, placebo-controlled, crossover, fully
      counterbalanced study. All participants underwent three different treatments:
      placebo (PL), CL, and SB. The dose was identical in all conditions: 500 mg/kg BM
      divided into four daily individual doses of 125 mg/kg BM, for five consecutive
      days, followed by a 2-7-day washout period. On the fifth day of supplementation,
      individuals undertook four 30-s Wingate bouts for upper body with 3-min recovery
      between bouts. Total mechanical work (TMW) for the overall protocol and for the
      initial (1st+2nd) and final (3rd+4th) bouts was determined at each session. Blood
      pH, bicarbonate, and lactate levels were determined at rest, immediately and 5
      min after exercise. CL supplementation did not affect performance (P > 0.05 for
      the overall TMW as well for initial and final bouts), nor did it affect blood
      bicarbonate and pH prior to exercise. SB supplementation improved performance by
      2.9% for overall TMW (P = 0.02) and 5.9% in the 3rd+4th bouts (P = 0001).
      Compared to the control session, SB also promoted higher increases in blood
      bicarbonate than CL and PL (+0.03 +/- 0.04 vs +0.009 +/- 0.02 and +0.01 +/- 0.03,
      respectively). CL supplementation was not capable of enhancing high-intensity
      intermittent performance or changing extracellular buffering capacity challenging
      the notion that this dietary supplement is an effective buffering agent.

PMID- 27882613
TI  - Improvements of Procedural Results With a New-Generation Self-Expanding
      Transfemoral Aortic Valve Prosthesis in Comparison to the Old-Generation Device.
AB  - OBJECTIVES: In this study, we compare procedural results of our first Evolut R
      (Medtronic, Minneapolis, MN, USA) implantations with the last CoreValve
      implantations. Main endpoints include paravalvular regurgitation, major vascular
      complications, stroke, and pacemaker implantation. BACKGROUND: The evolution of
      transcatheter aortic valve replacement (TAVR) was possible due to various
      technical improvements, leading to better periprocedural and long-term outcome.
      The newly designed Evolut R valve has the potential to further improve TAVR's
      performance. METHODS: We retrospectively analyzed our first 100 consecutive
      patients who received the Evolut R valve with the last 100 consecutive patients
      who received the CoreValve prosthesis between July 2013 and February 2016. Only
      patients treated with a 26 mm or 29 mm bioprosthesis were included. RESULTS: No
      significant differences in patient characteristics were noticed. Both angiography
      and echocardiography after TAVR showed significantly higher rates of "none or
      trace" regurgitation in the Evolut R group (angiography: 67% Evolut R vs. 29.3%
      CoreValve; P < 0.001; echocardiography: 68% Evolut R vs. 46.5% CoreValve; P <
      0.05). No significant differences were seen in 30-day mortality (7% CoreValve vs.
      1% Evolut R), stroke rates (3% CoreValve vs. 2% Evolut R), pacemaker implantation
      rates (24% CoreValve vs. 23% Evolut R), and major vascular complications (6%
      CoreValve vs. 1% Evolut R). Implantations were significantly higher with the
      Evolut R prosthesis. CONCLUSIONS: TAVR with the new Evolut R resulted in
      significantly lower paravalvular regurgitation. This may be due to redesigned
      cell geometry and higher precision during implantations, as well as the ability
      to resheath a malpositioned valve.

PMID- 27882614
TI  - alpha-Ketoglutarate dehydrogenase complex moonlighting: ROS signalling added to
      the list: An Editorial highlight for 'Reductions in the mitochondrial enzyme
      alpha-ketoglutarate dehydrogenase complex in neurodegenerative disease -
      beneficial or detrimental?'
AB  - Read the highlighted article 'Reductions in the mitochondrial enzyme alpha
      ketoglutarate dehydrogenase complex in neurodegenerative disease - beneficial or
      detrimental?' on page 823.

PMID- 27882615
TI  - Development of Glassy Bicontinuous Cubic Liquid Crystals for Solid Proton
      Conductive Materials.
AB  - Glassy bicontinuous cubic liquid crystals are developed to be a matrix having a
      hydrophilic infinite periodic minimal surface (IPMS). They function as a scaffold
      for water, leading to the formation of a 3D continuous hydrogen-bonding network
      of water molecules along the IPMS. This material design is advantageous for
      developing novel electrolytes with rigidity and high proton conductivity.

PMID- 27882616
TI  - Defect-Resistant Radiative Performance of m-Plane Immiscible Al1-x Inx N
      Epitaxial Nanostructures for Deep-Ultraviolet and Visible Polarized Light
      Emitters.
AB  - Planar vacuum-fluorescent-display devices emitting polarized UV-C, blue, and
      green light are demonstrated using immiscible Al1-x Inx N nanostructures grown in
      nonpolar m-directions. Despite the presence of high concentration of nonradiative
      recombination centers, the Al1-x Inx N nanostructures emit polarized light with
      the luminescence lifetimes of 22-32 ps at 300 K. This defect-resistant radiative
      performance suggests supernormal localized characteristics of electron-hole
      pairs.

PMID- 27882617
TI  - Heritability estimates of muscle strength-related phenotypes: A systematic review
      and meta-analysis.
AB  - The purpose of this study was to clarify the heritability estimates of human
      muscle strength-related phenotypes (H2 -msp). A systematic literature search was
      conducted using PubMed (through August 22, 2016). Studies reporting the H2 -msp
      for healthy subjects in a sedentary state were included. Random-effects models
      were used to calculate the weighted mean heritability estimates. Moreover,
      subgroup analyses were performed based on phenotypic categories (eg, grip
      strength, isotonic strength, jumping ability). Sensitivity analyses were also
      conducted to investigate potential sources of heterogeneity of H2 -msp, which
      included age and sex. Twenty-four articles including 58 measurements were
      included in the meta-analysis. The weighted mean H2 -msp for all 58 measurements
      was 0.52 (95% confidence intervals [CI]: 0.48-0.56), with high heterogeneity (I2
      =91.0%, P<.001). Subgroup analysis showed that the heritability of isometric grip
      strength, other isometric strength, isotonic strength, isokinetic strength,
      jumping ability, and other power measurements was 0.56 (95% CI: 0.46-0.67), 0.49
      (0.47-0.52), 0.49 (0.32-0.67), 0.49 (0.37-0.61), 0.55 (0.45-0.65), and 0.51 (0.31
      0.70), respectively. The H2 -msp decreased with age (P<.05). In conclusion, our
      results indicate that the influence of genetic and environmental factors on
      muscle strength-related phenotypes is comparable. Moreover, the role of
      environmental factors increased with age. These findings may contribute toward an
      understanding of muscle strength-related phenotypes.

PMID- 27882618
TI  - Whole genome sequencing analysis of the cutaneous pathogenic yeast Malassezia
      restricta and identification of the major lipase expressed on the scalp of
      patients with dandruff.
AB  - Malassezia species are opportunistic pathogenic fungi that are frequently
      associated with seborrhoeic dermatitis, including dandruff. Most Malassezia
      species are lipid dependent, a property that is compensated by breaking down host
      sebum into fatty acids by lipases. In this study, we aimed to sequence and
      analyse the whole genome of Malassezia restricta KCTC 27527, a clinical isolate
      from a Korean patient with severe dandruff, to search for lipase orthologues and
      identify the lipase that is the most frequently expressed on the scalp of
      patients with dandruff. The genome of M. restricta KCTC 27527 was sequenced using
      the Illumina MiSeq and PacBio platforms. Lipase orthologues were identified by
      comparison with known lipase genes in the genomes of Malassezia globosa and
      Malassezia sympodialis. The expression of the identified lipase genes was
      directly evaluated in swab samples from the scalps of 56 patients with dandruff.
      We found that, among the identified lipase-encoding genes, the gene encoding
      lipase homolog MRES_03670, named LIP5 in this study, was the most frequently
      expressed lipase in the swab samples. Our study provides an overview of the
      genome of a clinical isolate of M. restricta and fundamental information for
      elucidating the role of lipases during fungus-host interaction.

PMID- 27882620
TI  - Temperature and Thickness Dependences of the Anisotropic In-Plane Thermal
      Conductivity of Black Phosphorus.
AB  - The anisotropic basal-plane thermal conductivities of thin black phosphorus
      obtained from a new four-probe measurement exhibit much higher peak values at low
      temperatures than previous reports. First principles calculations reveal the
      important role of crystal defects and weak thickness dependence that is opposite
      to the case of graphene and graphite due to the absence of reflection symmetry in
      puckered phosphorene.

PMID- 27882619
TI  - In Operando Mechanism Analysis on Nanocrystalline Silicon Anode Material for
      Reversible and Ultrafast Sodium Storage.
AB  - The electrochemical mechanism of nanocrystalline silicon anode in sodium ion
      batteries is first studied via in operando Raman and in operando X-ray
      diffraction. An irreversible structural conversion from crystalline silicon to
      amorphous silicon takes place during the initial cycles, leading to ultrafast
      reversible sodium insertion in the newly generated amorphous silicon.
      Furthermore, an optimized silicon/carbon composite has been developed to further
      improve its electrochemical performance.

PMID- 27882621
TI  - YouTube as a source for parents' education on early childhood caries.
AB  - BACKGROUND: Patients can and do search the Internet for information on various
      health-related topics. YouTubeTM is one popular website they may consult. AIM: To
      examine the quality of information offered by YouTubeTM for patients seeking
      information on early childhood caries (ECC). DESIGN: YouTubeTM was searched for
      videos on ECC. The usefulness of selected videos in providing adequate
      information about ECC was evaluated using a 13-point usefulness score. The
      guidelines of the American Academy of Pediatric Dentistry were used for
      benchmarking. RESULTS: Most videos were uploaded by healthcare professionals
      (60%, n = 18). Videos had generally low usefulness scores (mean: 5.1 +/- 2.9;
      range: 1-11). An average YouTubeTM video on ECC was viewed two times/day (range:
      0.07-34.4 views/day). Less useful videos ranked early on the viewing list, and
      viewer's interactions with videos were not affected significantly by their
      usefulness. CONCLUSION: YouTubeTM should not be used as a trusted site for
      educating patients on ECC.

PMID- 27882622
TI  - Black Phosphorus Nanosheet-Based Drug Delivery System for Synergistic
      Photodynamic/Photothermal/Chemotherapy of Cancer.
AB  - A black phosphorus (BP)-based drug delivery system for synergistic
      photodynamic/photothermal/chemotherapy of cancer is constructed. As a 2D
      nanosheet, BP shows super high drug loading capacity and pH-/photoresponsive drug
      release. The intrinsic photothermal and photodynamic effects of BP enhance the
      antitumor activities. The synergistic photodynamic/photothermal/chemotherapy
      makes BP-based drug delivery system a multifunctional nanomedicine platform.

PMID- 27882624
TI  - Fluorographene Modified by Grignard Reagents: A Broad Range of Functional
      Nanomaterials.
AB  - Fluorographene is the youngest stoichiometric derivative of graphene; hence, its
      reactivity is only poorly explored. Compared to graphene, the significantly
      higher reactivity of C-F bonds makes this material a suitable platform for a
      large number of chemical modifications. Fluorographene is also the only member of
      the halographene family that can be prepared in the stoichiometric composition
      (C1 F1 ). Herein, the chemical modification of fluorographene with Grignard
      reagents, which are well known in organic synthesis for the formation of new C-C
      bonds, is presented. The reaction with alkyl magnesium bromides led to successful
      modification of fluorographene with ethyl, vinyl, ethynyl and propargyl groups.
      Chemical characterisation showed the presence of covalently bonded functional
      groups in a high concentration exceeding one functional group per C6 motif. The
      reactivity of Grignard reagents with fluorographene decreased from ethyl to
      ethynyl. The terminal carbon-carbon triple bonds were used for click reactions
      with organic azides leading to the formation of triazole rings. These findings
      open up a broad spectrum of opportunities for simple and robust modification of
      graphene by chemical reactions proceeding at room temperature under mild
      conditions. These results have major application potential in sensing, biomedical
      and energy-related applications.

PMID- 27882623
TI  - Concise Review: Stem Cell-Based Treatment of Pelizaeus-Merzbacher Disease.
AB  - Pelizaeus-Merzbacher disease (PMD) is an X-linked disorder caused by mutation in
      the proteolipid protein-1 (PLP1) gene, which encodes the proteolipid protein of
      myelinating oligodendroglia. PMD exhibits phenotypic variability that reflects
      its considerable genotypic heterogeneity, but all forms of the disease result in
      central hypomyelination, associated in most cases with early neurological
      dysfunction, progressive deterioration, and ultimately death. PMD may present as
      a connatal, classic and transitional forms, or as the less severe spastic
      paraplegia type 2 and PLP-null phenotypes. These disorders are most often
      associated with duplications of the PLP1 gene, but can also be caused by coding
      and noncoding point mutations as well as full or partial deletion of the gene. A
      number of genetically-distinct but phenotypically-similar disorders of
      hypomyelination exist which, like PMD, lack any effective therapy. Yet as
      relatively pure CNS hypomyelinating disorders, with limited involvement of the
      PNS and relatively little attendant neuronal pathology, PMD and similar
      hypomyelinating disorders are attractive therapeutic targets for neural stem cell
      and glial progenitor cell transplantation, efforts at which are now underway in a
      number of research centers. Stem Cells 2017;35:311-315.

PMID- 27882626
TI  - Spectrophotometric color analysis of maxillary permanent central incisors in a
      pediatric population: a preliminary study.
AB  - BACKGROUND: Although several studies have reported the color distribution of
      maxillary central incisors and the effects of age and gender, a reliable database
      of the color of newly erupted teeth with open apices and the effect of the root
      development stage on tooth color shades do not currently exist. AIM: The purpose
      of this in vivo study was to perform a spectrophotometric color analysis of
      maxillary permanent central incisors based on apical developmental stage, age,
      and gender groups. DESIGN: A total of 734 maxillary permanent central incisors
      from 367 children aged 7-18 years who have fully erupted, intact, unrestored,
      vital right and left maxillary central incisors were evaluated. The patients were
      divided into nine groups, according to the root development stage and age.
      Digital images were quantified by non-contact spectrophotometry to determine the
      tooth color. Each tooth's color shade and L*, a*, and b* values were recorded.
      The L*, a*, and b* values were analyzed statistically with a multivariate
      analysis of variance test, and the color shades were analyzed with chi-square
      tests at the alpha = 0.05 level. RESULTS: The most common general tooth shade,
      for both genders, was A2. A statistically significant difference was found
      between the 7- to 12-year-old and 13- to 18-year-old age groups in the general
      tooth shade and its L* value in the overall, cervical, middle, and incisal sites
      (P < 0.05). CONCLUSION: There is a strong relationship between the apical
      developmental stages of the teeth and the L* values.

PMID- 27882625
TI  - Review of high-risk features of cutaneous squamous cell carcinoma and
      discrepancies between the American Joint Committee on Cancer and NCCN Clinical
      Practice Guidelines In Oncology.
AB  - Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from
      epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily
      treated without further complication, some behave more aggressively and carry a
      poor prognosis. These "high-risk" cutaneous SCCs commonly originate in the head
      and neck and have an increased tendency toward recurrence, local invasion, and
      distant metastasis. Factors for high-risk cutaneous SCC include large size (>2
      cm), a deeply invasive lesion (>2 mm), incomplete excision, high
      grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion,
      immunosuppression, and high-risk anatomic locations. Both the National
      Comprehensive Cancer Network(r) (NCCN(r) ) and the American Joint Committee on
      Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The
      purpose of this article was to review the high-risk features included in these
      guidelines, as well as their notable discrepancies and omissions. We also provide
      a brief overview of current prophylactic measures, surgical options, and adjuvant
      therapies for high-risk cutaneous SCC. (c) 2016 Wiley Periodicals, Inc. Head Neck
      39: 578-594, 2017.

PMID- 27882627
TI  - Small Photoblinking Semiconductor Polymer Dots for Fluorescence Nanoscopy.
AB  - Two types of small photoblinking Pdots with high brightness, strong
      photostability, and favorable biocompatibility, are designed. Super-resolution
      optical fluctuation imaging is achieved using these Pdots. Imaging of subcellular
      structures demonstrates that these small photoblinking Pdots are outstanding
      probes for fast, long-term super-resolution fluorescence imaging.

PMID- 27882628
TI  - The influence of testicular microlithiasis on the outcomes of in vitro
      fertilisation in a Chinese Han population.
AB  - To investigate the influence of testicular microlithiasis (TM) on the outcomes of
      in vitro fertilisation (IVF), we retrospectively reviewed the ultrasonography
      results of the TM patients who underwent IVF treatment in our hospital. They were
      classified as classic-TM (CTM) or limited-TM (LTM) comparing with patients
      without TM (Non-TM). Semen parameters, rates of fertilisation, normal
      fertilisation, good embryos and clinical pregnancy were analysed. The Non-TM
      group showed higher percentage of morphologically normal spermatozoa than the CTM
      or LTM group (4.08 +/- 2.07 versus 3.40 +/- 2.00 versus 3.04 +/- 1.66, p = .003)
      while the other general semen parameters were comparable. The LTM group showed
      higher rate of fertilisation than the CTM group (85.10% versus 81.12%, p = .044).
      Moreover, the rates of normal fertilisation of Non-TM (62.47%) and LTM (66.32%)
      group were significantly higher than the CTM (58.02%) group (p = .027 and p =
      .001 respectively). There were 333 embryo transfer cycles in total (including 222
      fresh and 111 frozen). The overall clinical pregnancy rate was 54.95%, 58.33% and
      64.12% in the group of CTM, LTM and Non-TM respectively. However, no
      statistically significant difference was obtained (p = .326). Our results suggest
      that TM may have influence on the IVF outcomes. The extent of microlithiasis
      correlates inversely with the rates of fertilisation and normal fertilisation.

PMID- 27882629
TI  - Average-Cost Pricing and Dynamic Selection Incentives in the Hospital Sector.
AB  - This study investigates dynamic incentives to select patients for hospitals that
      are remunerated according to a prospective payment system of the diagnosis
      related group (DRG) type. Using a model with patients differing in severity
      within a DRG, we show that price dynamics depend on the extent of hospital
      altruism and the relation between patients' severity and benefit. Upwards and
      downwards price movements over time are both possible. In a steady state, DRG
      prices are unlikely to give optimal incentives to treat patients. Depending on
      the level of altruism, too few or too many patients are treated. DRG pricing may
      also give incentives to treat low-severity patients even though high-severity
      patients should be treated. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27882630
TI  - Workplace stress, burnout and coping: a qualitative study of the experiences of
      Australian disability support workers.
AB  - Disability support workers (DSWs) are the backbone of contemporary disability
      support services and the interface through which disability philosophies and
      policies are translated into practical action. DSWs often experience workplace
      stress and burnout, resulting in a high turnover rate of employees within the non
      professional disability service workforce. The full implementation of the
      National Disability Insurance Scheme in Australia is set to intensify the current
      challenges of attracting and retaining DSWs, as the role becomes characterised by
      greater demands, ambiguity and conflict. The aim of this study was to explore
      DSWs' perceptions of enjoyable and challenging aspects of disability support
      work, sources of stress and burnout and the strategies they use to cope when
      these issues arise. Twelve DSWs workers providing support for adults living with
      intellectual and physical disabilities were interviewed. Thematic analysis
      revealed a superordinate theme of 'Balance' comprising three sub-themes:
      'Balancing Negatives and Positives', 'Periods of Imbalance', and 'Strategies to
      Reclaim Balance'. Participants spoke of the rewarding and uplifting times in
      their job such as watching a client learn new skills and being shown
      appreciation. These moments were contrasted by emotionally and physically
      draining aspects of their work, including challenging client behaviour, earning a
      low income, and having limited power to make decisions. Participants described
      periods of imbalance, wherein the negatives of their job outweighed the
      positives, resulting in stress and sometimes burnout. Participants often had to
      actively seek support and tended to rely on their own strategies to manage
      stress. Findings suggest that organisational support together with workplace
      interventions that support DSWs to perceive the positive aspects of their work,
      such as acceptance and mindfulness-based approaches, may help to limit
      experiences of stress and burnout. The further development and evaluation of
      emotion-focused workplace therapies, and interventions that consider
      organisational (macro) factors is suggested.

PMID- 27882631
TI  - Adolescents' inhibitory control: keep it cool or lose control.
AB  - Inhibitory control (i.e., the ability to resist automatisms, temptations,
      distractions, or interference and to adapt to conflicting situations) is a
      determinant of cognitive and socio-emotional development. In light of the
      discrepancies of previous findings on the development of inhibitory control in
      affectively charged contexts, two important issues need to be addressed. We need
      to determine (a) whether cool inhibitory control (in affectively neutral
      contexts) and hot inhibitory control (in affectively charged contexts) follow the
      same developmental pattern and (b) the degree of specificity of these two types
      of inhibitory control at different ages. Thus, in the present study, we
      investigated the developmental patterns of cool and hot inhibitory control and
      the degree of specificity of these abilities in children, adolescents and adults.
      Typically developing children, adolescents, and adults performed two Stroop-like
      tasks: an affectively neutral one (Cool Stroop task) and an affectively charged
      one (Hot Stroop task). In the Cool Stroop task, the participants were asked to
      identify the ink color of the words independent of color that the words named; in
      the Hot Stroop task, the participants were asked to identify the emotional
      expression of a face independent of the emotion named by a simultaneously
      displayed written word. We found that cool inhibitory control abilities develop
      linearly with age, whereas hot inhibitory control abilities follow a quadratic
      developmental pattern, with adolescents displaying worse hot inhibitory control
      abilities than children and adults. In addition, cool and hot inhibitory control
      abilities were correlated in children but not in adolescents and adults. The
      present study suggests (a) that cool and hot inhibitory control abilities develop
      differently from childhood to adulthood - i.e., that cool inhibition follows a
      linear developmental pattern and hot inhibition follows an adolescent-specific
      pattern - and (b) that they become progressively more domain-specific with age.

PMID- 27882632
TI  - Rocking the boat: does perfect rowing crew synchronization reduce detrimental
      boat movements?
AB  - In crew rowing, crew members need to mutually synchronize their movements to
      achieve optimal crew performance. Intuitively, poor crew coordination is often
      deemed to involve additional boat movements such as surge velocity fluctuations,
      heave, pitch, and roll, which would imply lower efficiency (eg, due to increased
      hydrodynamic drag). The aim of this study was to investigate this alleged
      relation between crew coordination and boat movements at different stroke rates.
      Fifteen crews of two rowers rowed in a double scull (ie, a two-person boat) at
      18, 22, 26, 30, and 34 strokes per minute. Oar angles (using potentiometers) and
      movements of the boat (using a three-axial accelerometer-gyroscope sensor) were
      measured (200 Hz). Results indicated that crew synchronization became more
      consistent with stroke rate, while surge, heave, and pitch fluctuations
      increased. Further, within each stroke rate condition, better crew
      synchronization was related to less roll of the boat, but increased fluctuations
      regarding surge, heave, and pitch. Together this demonstrates that while better
      crew synchronization relates to enhanced lateral stability of the boat, it
      inevitably involves more detrimental boat movements and hence involves lower
      biomechanical efficiency.

PMID- 27882635
TI  - A bilingual advantage in 54-month-olds' use of referential cues in fast mapping.
AB  - Research has demonstrated a bilingual advantage in how young children use
      referential cues such as eye gaze and pointing gesture to locate an object or to
      categorize objects. This study investigated the use of referential cues (i.e. eye
      gaze) in fast mapping in three groups of children that differed in their language
      exposure. One hundred and seven 54-month-old children who were English
      monolinguals (n = 28), English-Mandarin bilinguals (n = 48), and English-Mandarin
      bilinguals with exposure to a third language (i.e. trilinguals, n = 31) were
      assessed with a word learning task using two types of test - a referent test and
      a mutual exclusivity test. During the task, following the gaze of an adult
      speaker was needed to be able to indicate the correct referent of a novel word at
      test. All three groups of children demonstrated successful word learning in
      explicit selection of and implicit looking time toward the target object during
      testing. However, bilingual and trilingual children outperformed their
      monolingual peers in both types of test when they were asked to explicitly select
      the correct objects. These findings suggest positive effects of bilingualism on
      children's use of referential cues in fast mapping.

PMID- 27882633
TI  - Tailoring Renal Clearance and Tumor Targeting of Ultrasmall Metal Nanoparticles
      with Particle Density.
AB  - Identifying key factors that govern the in vivo behavior of nanomaterials is
      critical to the clinical translation of nanomedicines. Overshadowed by size-,
      shape-, and surface-chemistry effects, the impact of the particle core density on
      clearance and tumor targeting of inorganic nanoparticles (NPs) remains largely
      unknown. By utilizing a class of ultrasmall metal NPs with the same size and
      surface chemistry but different densities, we found that the renal-clearance
      efficiency exponentially increased in the early elimination phase while passive
      tumor targeting linearly decreased with a decrease in particle density. Moreover,
      lower-density NPs are more easily distributed in the body and have shorter
      retention times in highly permeable organs than higher-density NPs. The density
      dependent in vivo behavior of metal NPs likely results from their distinct
      margination in laminar blood flow, which opens up a new path for precise control
      of nanomedicines in vivo.

PMID- 27882634
TI  - Attachment and couple satisfaction as predictors of expressed emotion in women
      facing breast cancer and their partners in the immediate post-surgery period.
AB  - OBJECTIVES: To investigate expressed emotion (EE) in couples facing breast cancer
      in the immediate post-surgery period. EE may be predictive of psychological
      disturbances that hinder both partners' capacities to cope with the stress of the
      disease. Severity of the disease, attachment tendencies, and couple satisfaction
      were tested as predictors of EE. DESIGN: The design was cross-sectional. Couples
      (N = 61) were interviewed 2 weeks after the women's breast surgery. METHODS:
      Expressed emotion was assessed in women and in partners with the Five-Minute
      Speech Sample, with a focus on overt and covert criticisms. Self-reported EE,
      attachment tendencies, and couple satisfaction were assessed with questionnaires.
      Hierarchical regression analyses were performed to test the predictors and
      possible interactions between them. RESULTS: Both partners expressed overt and
      covert criticisms; women expressed more overt criticisms than did their partners.
      Cancer stage was inversely related to the number of overt criticisms in women and
      to the number of covert criticisms in partners. Regression analyses showed that
      in women, higher attachment anxiety and lower couple satisfaction were positive
      predictors of overt criticisms; in partners, a higher cancer stage was a negative
      predictor of overt and covert criticisms. CONCLUSIONS: Practitioners should pay
      attention to the couple relationship in breast cancer. EE is most likely to
      appear when the cancer stage is low, showing that even when the medical prognosis
      is optimal, relational and emotional disturbances may occur. Statement of
      contribution What is already known on this subject? The couple relationship is of
      paramount importance in breast cancer. Expressed emotion (EE) is related to
      negative individual and relational psychological outcomes in psychiatric and
      somatic diseases. Expressed emotion has not yet been studied in the context of
      breast cancer. What does this study add? Expressed emotion is present in breast
      cancer situations, especially when the cancer stage is low. There was more EE in
      women than in their partners. Cancer stage, attachment tendencies, and couple
      satisfaction are predictors of EE.

PMID- 27882636
TI  - Fear of knowledge: Clinical hypotheses in diagnostic and prognostic reasoning.
AB  - Patients are interested in receiving accurate diagnostic and prognostic
      information. Models and reasoning about diagnoses have been extensively
      investigated from a foundational perspective; however, for all its importance,
      prognosis has yet to receive a comparable degree of philosophical and
      methodological attention, and this may be due to the difficulties inherent in
      accurate prognostics. In the light of these considerations, we discuss a
      considerable body of critical thinking on the topic of prognostication and its
      strict relations with diagnostic reasoning, pointing out the distinction between
      nosographic and pathophysiological types of diagnosis and prognosis, underlying
      the importance of the explication and explanation processes. We then distinguish
      between various forms of hypothetical reasoning applied to reach diagnostic and
      prognostic judgments, comparing them with specific forms of abductive reasoning.
      The main thesis is that creative abduction regarding clinical hypotheses in
      diagnostic process is very unlikely to occur, whereas this seems to be often the
      case for prognostic judgments. The reasons behind this distinction are due to the
      different types of uncertainty involved in diagnostic and prognostic judgments.

PMID- 27882637
TI  - Transplantation-associated thrombotic microangiopathy isolated to a congenital
      anomaly of the lung.
AB  - TA-TMA is a post-hematopoietic stem cell transplant complication with clinical
      features of hemolytic anemia and thrombocytopenia. A 26-month-old child who had
      had an allogeneic transplant for treatment of DBA developed severe TA-TMA with
      heavy red blood cell and platelet transfusion dependence. Incidentally, he was
      found to have a lung sequestration. TA-TMA resolved and transfusion dependence
      resolved after resection of the sequestration. The finding suggests the
      malformation vasculature was selectively vulnerable to the trigger of TA-TMA
      raising perhaps a clue to basic pathophysiology of TA-TMA and/or vascular
      malformations.

PMID- 27882638
TI  - Anxiety symptoms prior to a prostate cancer diagnosis: Associations with
      knowledge and openness to treatment.
AB  - AIM: Research suggests that anxiety may be a common response to a cancer
      diagnosis, but research is needed to examine anxiety before diagnosis. Anxiety
      before diagnosis may relate to the comprehension of relevant health information
      or openness to potential treatments. This study examined anxiety and these
      outcomes in men who were waiting to learn of a prostate cancer diagnosis.
      OBJECTIVES: One goal of this study was to determine whether anxiety would
      increase as men came closer to learning the results of their prostate cancer
      biopsy. Another goal was to test whether anxiety was associated with knowledge
      about prostate cancer or openness to different treatments. METHODS: Men (N = 265)
      who were facing a prostate cancer diagnosis were surveyed at two time points.
      Time 1 occurred at the time of biopsy, and Time 2 occurred immediately before men
      received their biopsy result. At each time point, men reported their anxiety
      about prostate cancer and their biopsy result. At Time 2, they completed a
      knowledge test of information about prostate cancer and reported their openness
      to different potential treatments. RESULTS: Anxiety symptoms increased as men
      came closer to learning their diagnosis. Also, higher anxiety was associated with
      lower knowledge and greater openness to particular treatments like surgery.
      Interactions showed that when anxiety increased from Time 1 to Time 2, having
      high or low knowledge mattered less to treatment openness. CONCLUSION: Waiting
      for a cancer diagnosis is an important time period in which anxiety may increase
      and relate to information processing and openness to treatments. Statement of
      contribution What is already known on this subject? Men undergoing prostate
      cancer screening have been found to experience high and low levels of anxiety.
      Research has shown that negative emotions like anxiety are common following a
      cancer diagnosis, but little research has examined emotions right before
      diagnosis. Anxiety has been associated with information processing and motivation
      to engage in preventive behaviours. What does this study add? Applies and tests a
      theoretical idea related to how anxiety may change as one approaches personally
      relevant threatening health feedback. Shows relationships between changes in
      anxiety and knowledge in the context of waiting for actual health feedback.
      Associates increased anxiety in the prostate cancer context with knowledge and
      openness to different treatments.

PMID- 27882639
TI  - Imaging the Atomic Position of Light Cations in a Porous Network and the
      Europium(III) Ion Exchange Capability by Aberration-Corrected Electron
      Microscopy.
AB  - In the present work, ETS-10 microporous titanosilicate has been synthesized and
      its structure characterized by means of powder XRD and aberration corrected
      scanning transmission electron microscopy (Cs -corrected STEM). For the first
      time, sodium ions have been imaged sitting inside the 7-membered rings. The ion
      exchange capability has been tested by the inclusion of rare earth metals (Eu, Tb
      and Gd) to produce a luminescent material which has been studied by atomic
      resolution Cs -corrected STEM. The data produced has allowed unambiguous imaging
      of light atoms in a microporous framework as well as determining the cationic
      metal positions for the first time, providing evidence of the importance of
      advanced electron microscopy methods for the study of the local environment of
      metals within zeolitic supports providing unique information of both systems
      (guest and support) at the same time.

PMID- 27882641
TI  - Hydrogen-Permeable Tubular Membrane Reactor: Promoting Conversion and Product
      Selectivity for Non-Oxidative Activation of Methane over an Fe(c)SiO2 Catalyst.
AB  - Non-oxidative methane conversion over Fe(c)SiO2 catalyst was studied for the
      first time in a hydrogen (H2 ) permeable tubular membrane reactor. The membrane
      reactor is composed of a mixed ionic-electronic SrCe0.7 Zr0.2 Eu0.1 O3-delta thin
      film (~20 MUm) supported on the outer surface of a one-end capped porous SrCe0.8
      Zr0.2 O3-delta tube. Significant improvement in CH4 conversion was achieved upon
      H2 removal from the membrane reactor compared to that in a fixed-bed reactor. The
      Fe(c)SiO2 catalyst in the H2 permeable membrane reactor demonstrated a stable ~30
      % C2+ single-pass yield, with up to 30 % CH4 conversion and 99 % selectivity to
      C2 (ethylene and acetylene) and aromatic (benzene and naphthalene) products, at
      the tested conditions. The selectivity towards C2 or aromatics was manipulated
      purposely by adding H2 into or removing H2 from the membrane reactor feed and
      permeate gas streams.

PMID- 27882640
TI  - Physiological markers of exercise capacity and lung disease severity in cystic
      fibrosis.
AB  - BACKGROUND AND OBJECTIVE: Peak aerobic capacity (VO2 peak) is an important
      outcome measure in cystic fibrosis (CF), but measurement is not widely available
      and can be influenced by patient motivation, pain and fatigue. Alternative
      markers of disease severity would be helpful. Neural respiratory drive, measured
      using parasternal intercostal muscle electromyography (EMGpara), reflects the
      load to capacity balance of the respiratory system and provides a composite
      measure of pulmonary function impairment in CF. The aim of the study was to
      investigate the relationship between exercise capacity, EMGpara and established
      measures of pulmonary function in clinically stable adult CF patients. METHODS:
      Twenty CF patients (12 males, median (range) age: 22.3 (17.0-43.1) years)
      performed the 10-m incremental shuttle walk test (ISWT) maximally with
      contemporaneous measures of aerobic metabolism. EMGpara was recorded from second
      intercostal space at rest and normalized using peak electromyogram activity
      obtained during maximum respiratory manoeuvres and expressed as EMGpara%max
      (EMGpara expressed as a percentage of maximum). RESULTS: VO2 peak was strongly
      correlated with ISWT distance (r = 0.864, P < 0.0001). Lung gas transfer (TL CO)
      % predicted was best correlated with VO2 peak (r = 0.842, P < 0.0001) and ISWT
      distance (r = 0.788, P < 0.0001). EMGpara%max also correlated with VO2 peak (
      0.757, P < 0.0001), while the relationships between exercise outcome measures and
      forced expiratory volume in 1 s (FEV1 ) % predicted and forced vital capacity
      (FVC) % predicted were less strong. A TL CO% predicted of <70.5% was the
      strongest predictor of VO2 peak <32 mL/min/kg (area under the curve (AUC): 0.96,
      100% sensitivity, 83.3% specificity). ISWT distance and EMGpara%max also
      performed well, with other pulmonary function variables demonstrating poorer
      predictive ability. CONCLUSION: TL CO% predicted and EMGpara%max relate strongly
      to exercise performance markers in CF and may provide alternative predictors of
      lung disease progression.

PMID- 27882642
TI  - Identifying mechanisms of change in a conversation therapy for aphasia using
      behaviour change theory and qualitative methods.
AB  - BACKGROUND: Conversation therapy for aphasia is a complex intervention comprising
      multiple components and targeting multiple outcomes. UK Medical Research Council
      (MRC) guidelines published in 2008 recommend that in addition to measuring the
      outcomes of complex interventions, evaluation should seek to clarify how such
      outcomes are produced, including identifying the hypothesized mechanisms of
      change. AIMS: To identify mechanisms of change within a conversation therapy for
      people with aphasia and their partners. Using qualitative methods, the study
      draws on behaviour change theory to understand how and why participants make
      changes in conversation during and after therapy. METHODS & PROCEDURES: Data were
      derived from 16 participants (eight people with aphasia; eight conversation
      partners) who were recruited to the Better Conversations with Aphasia research
      project and took part in an eight session conversation therapy programme. The
      dataset consists of in-therapy discussions and post-therapy interviews, which are
      analysed using Framework Analysis. OUTCOMES & RESULTS: Seven mechanisms of
      conversational behaviour change are identified and linked to theory. These show
      how therapy can activate changes to speakers' skills and motivation for using
      specific behaviours, and to the conversational opportunities available for
      strategy use. CONCLUSIONS & IMPLICATIONS: These clinically relevant findings
      offer guidance about the processes involved in producing behavioural change via
      conversation therapy. A distinction is made between the process involved in
      motivating change and that involved in embedding change. Differences are also
      noted between the process engaged in reducing unhelpful behaviour and that
      supporting new uses of compensatory strategies. Findings are expected to have
      benefits for those seeking to replicate therapy's core processes both in clinical
      practice and in future research.

PMID- 27882643
TI  - Micelles, Bicelles, and Nanodiscs: Comparing the Impact of Membrane Mimetics on
      Membrane Protein Backbone Dynamics.
AB  - Detergents are often used to investigate the structure and dynamics of membrane
      proteins. Whereas the structural integrity seems to be preserved in detergents
      for many membrane proteins, their functional activity is frequently compromised,
      but can be restored in a lipid environment. Herein we show with per-residue
      resolution that while OmpX forms a stable beta-barrel in DPC detergent micelles,
      DHPC/DMPC bicelles, and DMPC nanodiscs, the pico- to nanosecond and micro- to
      millisecond motions differ substantially between the detergent and lipid
      environment. In particular for the beta-strands, there is pronounced dynamic
      variability in the lipid environment, which appears to be suppressed in micelles.
      This unexpected complex and membrane-mimetic-dependent dynamic behavior indicates
      that the frequent loss of membrane protein activity in detergents might be
      related to reduced internal dynamics and that membrane protein activity
      correlates with lipid flexibility.

PMID- 27882644
TI  - Sleep-wake cycle phenotypes in young people with familial and non-familial mood
      disorders.
AB  - OBJECTIVES: Converging evidence identifies that the offspring of parents with
      bipolar disorder (BD), individuals at clinical high risk of BD, and young people
      with recent onset BD may differ from other clinical cases or healthy controls in
      terms of sleep-wake profiles. However, it is possible that these differences may
      reflect current mental state, subtype of mood disorder, or familial traits. This
      study aimed to determine objective and subjective sleep-wake profiles in
      individuals aged 15-25 years with a current major depressive episode, in relation
      to familial traits. METHODS: Frequency matching was employed to ensure that each
      individual with a confirmed family history of BD (FH+) could be compared to four
      controls who did not have a familial mood disorder (FH-). Pre-selected objective
      actigraphy and subjective Pittsburgh Sleep Quality Index (PSQI) ratings were
      compared using one-way analysis of variance (ANOVA) and applying the Benjamini
      Hochberg (BH) correction for false discoveries. RESULTS: The sample comprised 60
      individuals with a mean age of 19 years. The FH+ (n=12) and FH- groups (n=48)
      differed on three key sleep parameters: mean sleep duration on week nights
      (P=.049), variability in waking after sleep onset (P=.038), and daily
      disturbances (PSQI dimension of sleep disturbance and daytime dysfunction;
      P=.01). CONCLUSIONS: The sleep profiles we identified in this study, especially
      the daily disturbances phenotype, provide support for research into
      endophenotypes for BD. Also, the findings may offer the opportunity for more
      tailored, personalized interventions that target specific components of the sleep
      wake cycle in individuals with a family history of BD.

PMID- 27882645
TI  - Long-term lithium treatment increases intracellular and extracellular brain
      derived neurotrophic factor (BDNF) in cortical and hippocampal neurons at
      subtherapeutic concentrations.
AB  - OBJECTIVES: The putative neuroprotective effects of lithium treatment rely on the
      fact that it modulates several homeostatic mechanisms involved in the
      neurotrophic response, autophagy, oxidative stress, inflammation, and
      mitochondrial function. Lithium is a well-established therapeutic option for the
      acute and long-term management of bipolar disorder and major depression. The aim
      of this study was to evaluate the effects of subtherapeutic and therapeutic
      concentrations of chronic lithium treatment on brain-derived neurotrophic factor
      (BDNF) synthesis and secretion. METHODS: Primary cultures of cortical and
      hippocampal neurons were treated with different subtherapeutic (0.02 and 0.2 mM)
      and therapeutic (2 mM) concentrations of chronic lithium treatment in cortical
      and hippocampal cell culture. RESULTS: Lithium treatment increased the
      intracellular protein expression of cortical neurons (10% at 0.02 mM) and
      hippocampal neurons (28% and 14% at 0.02 mM and 0.2 mM, respectively).
      Extracellular BDNF of cortical neurons increased 30% and 428% at 0.02 and 0.2 mM,
      respectively and in hippocampal neurons increased 44% at 0.02 mM. CONCLUSION: The
      present study indicates that chronic, low-dose lithium treatment up-regulates
      BDNF production in primary neuronal cell culture.

PMID- 27882646
TI  - SymB and SymC, two membrane associated proteins, are required for Epichloe
      festucae hyphal cell-cell fusion and maintenance of a mutualistic interaction
      with Lolium perenne.
AB  - Cell-cell fusion in fungi is required for colony formation, nutrient transfer and
      signal transduction. Disruption of genes required for hyphal fusion in Epichloe
      festucae, a mutualistic symbiont of Lolium grasses, severely disrupts the host
      interaction phenotype. They examined whether symB and symC, the E. festucae
      homologs of Podospora anserina self-signaling genes IDC2 and IDC3, are required
      for E. festucae hyphal fusion and host symbiosis. Deletion mutants of these genes
      were defective in hyphal cell fusion, formed intra-hyphal hyphae, and had
      enhanced conidiation. SymB-GFP and SymC-mRFP1 localize to plasma membrane, septa
      and points of hyphal cell fusion. Plants infected with DeltasymB and DeltasymC
      strains were severely stunted. Hyphae of the mutants colonized vascular bundles,
      were more abundant than wild type in the intercellular spaces and formed intra
      hyphal hyphae. Although these phenotypes are identical to those previously
      observed for cell wall integrity MAP kinase mutants no difference was observed in
      the basal level of MpkA phosphorylation or its cellular localization in the
      mutant backgrounds. Both genes contain binding sites for the transcription factor
      ProA. Collectively these results show that SymB and SymC are key components of a
      conserved signaling network for E. festucae to maintain a mutualistic symbiotic
      interaction within L. perenne.

PMID- 27882648
TI  - Culture and its influences on dental education.
AB  - INTRODUCTION: Culture is an important factor influencing how students develop
      learning and how educators provide support to students. The aim of this paper is
      to explore a concept of national European cultures, and relationships between
      culture and educational practice with the intention of helping the dental
      profession gain a better understanding of effective teaching and learning in
      dentistry. CONTENT: Culture represents the collective behaviours, values and
      beliefs of people in a society. How people react to education is partly explained
      by culture. Students utilise different culturally based strategies to develop
      learning. We apply Hofstede's model to explore European cultures and implications
      for dental education and educational practice. Most Western students possess
      assimilating learning styles enabling them to learn effectively in student
      centred contexts while most Eastern students have accommodating learning styles
      and are more familiar with teacher-centred learning. Eastern students may need to
      adapt their approach to learning to better benefit from student-centred learning.
      CONCLUSION: Culture influences students' learning and educational practice.
      Dental educators should be aware of such influences and provide support that
      acknowledges students' different cultural backgrounds. Cultural competence is
      fundamental for effective teaching and learning in dentistry.

PMID- 27882647
TI  - Host and tissue variations overshadow the response of boreal moss-associated
      fungal communities to increased nitrogen load.
AB  - Human activity has more than doubled the amount of nitrogen entering the global
      nitrogen cycle, and the boreal forest biome is a nitrogen-limited ecosystem
      sensitive to nitrogen load perturbation. Although bryophyte-associated microbes
      contribute significantly to boreal forest ecosystem function, particularly in
      carbon and nitrogen cycling, little is known about their responses to
      anthropogenic global change. Amplicon pyrosequencing of the ITS2 region of rDNA
      was used to investigate how fungal communities associated with three bryophyte
      species responded to increased nitrogen loads in a long-term fertilization
      experiment in a boreal Picea abies forest in southern Norway. Overall, OTU
      richness, community composition and the relative abundance of specific ecological
      guilds were primarily influenced by host species identity and tissue type.
      Although not the primary factor affecting fungal communities, nitrogen addition
      did impact the abundance of specific guilds of fungi and the resulting overall
      community composition. Increased nitrogen loads decreased ectomycorrhizal
      abundance, with Amphinema, Cortinarius, Russula and Tylospora OTUs responding
      negatively to fertilization. Pathogen abundance increased with fertilization,
      particularly in the moss pathogen Eocronartium. Saprophytic fungi were both
      positively and negatively impacted by the nitrogen addition, indicating a complex
      community level response. The overshadowing of the effects of increased nitrogen
      loads by variation related to host and tissue type highlights the complexity of
      bryophyte-associated microbial communities and the intricate nature of their
      responses to anthropogenic global change.

PMID- 27882649
TI  - Impact of male condition on his spermatophore and consequences for female
      reproductive performance in the Glanville fritillary butterfly.
AB  - In butterflies, male reproductive success is highly related to the quality and
      the size of the spermatophore transferred to the female. The spermatophore is a
      capsule produced by the male during copulation, which in many species contains
      sperm in addition to a nuptial gift, and which is digested by the female after
      copulation. The nuptial gift may contribute to egg production and offspring
      quality, and in some cases also to female body maintenance. The production of the
      spermatophore, however, represents a cost for the male and, in polyandrous
      species, ejaculates are sometimes allocated adaptively across matings.
      Nonetheless, although the ecological factors affecting the reproductive success
      of female butterflies have been the topic of numerous studies, little information
      exists on the factors affecting males' contribution to reproduction, and the
      indirect impacts on female fecundity and fitness. We used the Glanville
      fritillary butterfly, Melitaea cinxia (Linnaeus, 1758) (Nymphalidae), in order to
      assess variation in male allocation to matings. In this species, smaller males
      produce smaller spermatophores, but variation in spermatophore size is not
      correlated with female reproductive success. We show that spermatophore size
      increases with male age at first mating, decreases with mating frequency and
      adult food-deprivation, and is not influenced by developmental food-limitation.
      The length of copulation period does not influence the spermatophore size nor
      influences the polyandrous mating behavior in this species. Male contribution to
      his spermatophore size is clearly influenced by his condition and adult-resource
      at the time of mating. Despite this variation, spermatophore size does not seem
      to have a direct impact on female reproductive output or mating behavior.

PMID- 27882650
TI  - A qualitative assessment of West Virginia pharmacist activities and attitude in
      diabetes management.
AB  - AIMS AND OBJECTIVES: The role of pharmacists in chronic disease state management
      has been shown to significantly improve patient health outcomes and reduce
      overall health care costs. The current study is designed to assess the roles and
      attitudes of West Virginia (WV) pharmacists toward diabetes, evaluate services
      provided, address pharmacist clinical understanding and training, and demonstrate
      the challenges that limit pharmacists ability to deliver an efficient disease
      state management. METHODS: We invited 435 preceptors affiliated with the
      University of Charleston School of Pharmacy to participate in the study using
      Qualtrics online survey software. The survey was divided into sections related to
      pharmacists, practice environment, pharmacist's roles in diabetes management, and
      challenges faced that limit their ability to deliver effective care to diabetic
      patients. Data were analyzed using 1-way analysis of variance, and a P value
      <=.05 was considered statistically significant. RESULTS: Of all eligible invited
      preceptors, 104 accessed the online survey based on the Qualtrics tracking tool,
      while 58 participated in the survey with a 56% response rate. Generally, WV
      pharmacists have positive attitudes regarding the provision of primary activities
      related to drug use and its associated problems. However, we report that WV
      pharmacists are less involved in providing education or recommendations regarding
      diabetes-associated risk factors such as nephropathy, retinopathy, foot care, and
      gastroparesis. In addition, the majority of pharmacists indicated that they face
      many challenges related to patient and the practice site environment that limit
      their ability to provide optimum diabetes patient care services. CONCLUSION:
      Despite the mounting evidence that pharmacists can improve diabetic patient
      outcomes while significantly reducing overall costs, WV pharmacists are less
      involved in providing education or counseling in a variety of areas related to
      disease state management. In addition, identifying pharmacist challenges provides
      significant information for future planning toward improving diabetic patient
      care.

PMID- 27882651
TI  - PANDAS in otolaryngology.

PMID- 27882652
TI  - Embryonic developmental process governing the conspicuousness of body stripes and
      blue tail coloration in the lizard Plestiodon latiscutatus.
AB  - The combination of body stripes and vivid blue tail color has independently
      evolved in different lizard families. To understand how and when lizards
      developed this coloration, we microscopically compared the embryonic development
      of pigment cells in two island populations of Plestiodon latiscutatus that
      exhibit either striped and blue tailed or inconspicuously striped and blue tailed
      juveniles, based on the newly determined 12 normal developmental stages of
      embryos from shortly after egg laying to just before hatching. We focus on the
      role of the melanophores in the body stripe and the role of iridophore
      morphotypes in the extent of blue tail coloration. The melanophore density in the
      black background region was higher in lizards with vivid stripes than in lizards
      with drab stripes. Iridophores started to fill the dermal space that was not yet
      occupied by melanophores, which resulted in a higher iridophore density in
      stripes than in the inter-stripe regions. We also discovered that iridophores
      with thin platelets reflecting blue structural coloration appeared at a specific
      region in the tail at stage 11. The position of the tail where iridophores
      emerged coincided with the boundary area separating anterior brown and green
      colored tail from posterior blue colored tail after hatching.

PMID- 27882654
TI  - Digital technologies as truth-bearers in health care.
AB  - In this paper, we explore the idea of digital technologies as truth-bearers in
      health care and argue that devices like SenseCam, which facilitate reflection and
      memory recall, have a potentially vital role in healthcare situations when
      questions of veracity are at stake (e.g., when best interest decisions are being
      made). We discuss the role of digital technologies as truth-bearers in the
      context of nursing people with dementia, as this is one area of health care in
      which the topic of truth-telling has been hotly debated. People with dementia
      have been excluded from research studies and decisions that affect their lives
      because they are not regarded as truth-bearers-that is, as being capable of
      giving truthful accounts of their experiences. Also, considerable research has
      focused on the ethics of lying to and deceiving people with dementia. Given their
      increasing prominence in healthcare settings, there has been surprisingly little
      discussion of what role digital technologies might play in relation to these
      questions of truth and deception. Drawing on theories from science and technology
      studies (STS), we explore their possible future role in some of the truth-making
      processes of health care. In particular, we discuss the potential value of
      constraints on use of SenseCam to support the accounts of people with dementia as
      part of their care.

PMID- 27882653
TI  - Synkinesis in Bell's palsy in a randomised controlled trial.
AB  - OBJECTIVES: To study the development of synkinesis in Bell's palsy. Frequency,
      severity, gender aspects and predictors were analysed. DESIGN: Data from the
      randomised controlled Scandinavian Bell's palsy trial including 829 patients.
      MAIN OUTCOME MEASURES: Frequency and severity of synkinesis at 12 months were the
      main outcome measures. Mean Sunnybrook synkinesis scores, voluntary movement
      scores and composite scores between 6 and 12 months were compared. RESULTS: In
      743 patients with a 12-month follow-up, synkinesis frequency was 21.3%. There was
      no gender difference. Synkinesis was moderate to severe in 6.6% of patients.
      Those with synkinesis at 6 months had a synkinesis score of 4.1 (+/-2.8 sd),
      which increased to 4.7 (+/-3.2) (P = 0.047) at 12 months (n = 93). Sunnybrook
      composite score at 1 month was the best predictor for synkinesis development with
      receiver operating characteristics and area under the curve (AUC) 0.87. Risk for
      synkinesis increased with a lower Sunnybrook composite score. Furthermore, at 1
      month, symmetry of voluntary movement had higher predictive value for synkinesis
      than resting symmetry with AUC 0.87 and 0.77, respectively. Gentle eye closure
      and open-mouth smile were the only independent significant predictive items (AUC
      0.86). CONCLUSIONS: Moderate-to-severe synkinesis was present in 6.6% of
      patients. The mean synkinesis score increased between 6 and 12 months, and
      outcome should therefore be evaluated after at least 12 months. Sunnybrook
      composite score and symmetry of voluntary movement at 1 month were good
      predictors for synkinesis.

PMID- 27882655
TI  - Situated technology in reproductive health care: Do we need a new theory of the
      subject to promote person-centred care?
AB  - Going through reproductive experiences (especially pregnancy and childbirth) in
      contemporary Western societies almost inevitably involves interaction with
      medical practitioners and various medical technologies in institutional context.
      This has important consequences for women as embodied subjects. A critical
      appraisal of these consequences-coming dominantly from feminist scholarship
      relied on a problematic theory of both technology and the subject, which are in
      contemporary approaches no longer considered as given, coherent and well
      individualized wholes, but as complex constellations that are locally situated
      and that can only be described empirically. In this study, we will be relying on
      the developments in phenomenological theory to reconceptualize women as
      technologically mediated embodied subjects and on the new paradigms in philosophy
      of technology and STS to reconstruct medical technology as situated-with the aim
      of reconceptualizing their relationship and exploring different possibilities for
      the mediating role of medical technology. It will be argued that technologization
      of female reproductive processes and alienating consequences for women are not
      necessary or directly interrelated. The role of technology varies from case to
      case and depends mainly on the nontechnological and relational aspects of
      institutional context, in which medical practitioners play a decisive role.

PMID- 27882656
TI  - Targeting Cancer with PCPA-Drug Conjugates: LSD1 Inhibition-Triggered Release of
      4-Hydroxytamoxifen.
AB  - Targeting cancer with small molecule prodrugs should help overcome problems
      associated with conventional cancer-targeting methods. Herein, we focused on
      lysine-specific demethylase 1 (LSD1) to trigger the controlled release of
      anticancer drugs in cancer cells, where LSD1 is highly expressed. Conjugates of
      the LSD1 inhibitor trans-2-phenylcyclopropylamine (PCPA) were used as novel
      prodrugs to selectively release anticancer drugs by LSD1 inhibition. As PCPA-drug
      conjugate (PDC) prototypes, we designed PCPA-tamoxifen conjugates 1 a and 1 b,
      which released 4-hydroxytamoxifen in the presence of LSD1 in vitro. Furthermore,
      1 a and 1 b inhibited the growth of breast cancer cells by the simultaneous
      inhibition of LSD1 and the estrogen receptor without exhibiting cytotoxicity
      toward normal cells. These results demonstrate that PDCs provide a useful prodrug
      method that may facilitate the selective release of drugs in cancer cells.

PMID- 27882657
TI  - Using a semi-conductor sequencing-based panel for genotyping of HPV-positive and
      HPV-negative oropharyngeal cancer: a retrospective pilot study.
AB  - OBJECTIVES: The aim of this study was to assess the feasibility of testing
      actionable mutations in small amounts of formalin-fixed paraffin-embedded
      material in multiple genes of the receptor tyrosine kinase pathway and to
      determine the frequency of these mutations in human papillomavirus (HPV)-positive
      and HPV-negative oropharyngeal cancer (OPC). DESIGN: A retrospective pilot study
      was performed. SETTING: In OPC, no predictive markers for response to epidermal
      growth factor receptor inhibition are known. Therefore, identifying predictive
      biomarkers is of utmost importance, but is often hampered by the small amount of
      tumour material available. PARTICIPANTS: We included the archival material of 45
      OPC, all treated with concomitant chemoradiotherapy between 2003 and 2010. MAIN
      OUTCOME MEASURES: Besides the HPV status, we assessed mutations using a gene
      panel that targets 16 genes in the receptor tyrosine kinase pathway and six other
      genes. The polymerase chain reaction required only 10 ng DNA. RESULTS: In total,
      42 of the 45 biopsies have been successfully analysed. In total 20 of 42 samples
      were HPV-positive and 22 of 42 were HPV-negative. In the receptor tyrosine kinase
      pathway, mutations in PIK3CA were most frequently identified. A TP53 mutation was
      identified in one HPV-positive sample and in 13 HPV-negative samples.
      Additionally, three mutations in three different genes were found. CONCLUSIONS:
      We evaluated an assay to identify mutations in the receptor tyrosine kinase
      pathway. As only small amounts of formalin-fixed paraffin-embedded material are
      sufficient for reliable analysis, this test opens up new possibilities for
      personalised medicine.

PMID- 27882658
TI  - Access to clinical trials for adolescents with soft tissue sarcomas: Enrollment
      in European pediatric Soft tissue sarcoma Study Group (EpSSG) protocols.
AB  - BACKGROUND: Adolescents with cancer are enrolled in clinical trials at far lower
      rates than children. This report compares the number of adolescents (15-19-year
      olds) and children (0-14-year-olds) enrolled in the protocols of the European
      pediatric Soft tissue sarcoma Study Group (EpSSG) with the number of cases
      expected to occur. METHODS: The observed-to-expected (O/E) ratio was detected in
      the EpSSG countries contributing most of the cases, that is, Italy, France,
      Spain, the Netherlands, United Kingdom, and Ireland. The observed cases included
      patients enrolled in any of the EpSSG protocols from October 2008 to October
      2015, when all EpSSG protocols were open in these countries. The number of
      expected cases was calculated from the incidence rates estimated throughout the
      RARECAREnet database in the countries' population-based cancer registries.
      RESULTS: In the countries considered, 2,118 cases aged 0-19 years were enrolled
      in the EpSSG trials from 2008 to 2015: 82.8% were children and 17.2% were
      adolescents. The O/E ratio was 0.30 among patients 15-19 years old, as opposed to
      0.64 for those 0-14 years old. The O/E ratio differed for the different subtypes:
      in adolescents, it was 0.64 and 0.18 for rhabdomyosarcoma (RMS) and non
      rhabdomyosarcoma soft tissue sarcomas (NRSTS), respectively; in children, it was
      0.77 and 0.50, respectively. The O/E ratios differed across the countries
      considered. CONCLUSIONS: Adolescents were less well represented than children on
      the EpSSG protocols, with better enrolment for RMS than for NRSTS for all age
      groups.

PMID- 27882660
TI  - Pediatric Dermatology Photoquiz: An Enlarging Facial Papule.

PMID- 27882659
TI  - Interventions for women who have a caesarean birth to increase uptake and
      duration of breastfeeding: A systematic review.
AB  - Rates of breastfeeding uptake are lower after a caesarean birth than vaginal
      birth, despite caesarean rates increasing globally over the past 30 years, and
      many high-income countries reporting overall caesarean rates of above 25%. A
      number of factors are likely to be associated with women's infant feeding
      decisions following a caesarean birth such as limited postoperative mobility,
      postoperative pain, and ongoing management of medical complications that may have
      triggered the need for a caesarean birth. The aim of this systematic review was
      to evaluate evidence of interventions on the initiation and duration of any and
      exclusive breastfeeding among women who had a planned or unplanned caesarean
      birth. Seven studies, presenting quantitative and qualitative evidence, published
      in the English language from January 1994 to February 2016 were included. A
      limited number of interventions were identified relevant to women who had had a
      caesarean birth. These included immediate or early skin-to-skin contact, parent
      education, the provision of sidecar bassinets when rooming-in, and use of breast
      pumps. Only one study, an intervention that included parent education and
      targeted breastfeeding support, increased initiation and continuation of
      breastfeeding, but due to methodological limitations, findings should be
      considered with caution. There is a need to better understand the impact of
      caesarean birth on maternal physiological, psychological, and physical recovery,
      the physiology of lactation and breastfeeding and infant feeding behaviors if
      effective interventions are to be implemented.

PMID- 27882662
TI  - Painful Pustular Groin Eruption in a Teenage Boy.

PMID- 27882661
TI  - Solitary Tumor on the Palm of a Young Boy.

PMID- 27882664
TI  - Discolored Fingertip and Dysesthesia of the Fingers in a 9-year-old Girl.

PMID- 27882663
TI  - Persistent Neck Rash in a 9-Year-Old Child.

PMID- 27882665
TI  - Subcutaneous Nodules and Stubby Hands.

PMID- 27882666
TI  - Painful Nodules on an Infant's Feet.

PMID- 27882667
TI  - Social Awareness Within Reach-Lessons from Pediatric Contact Dermatitis.

PMID- 27882670
TI  - Facial Eruption in a 5-year-Old Child with Acute Lymphoblastic Leukemia.

PMID- 27882668
TI  - Drug Reaction with Eosinophilia and Systemic Symptoms or Herpes Virus Infection:
      Author's Reply.

PMID- 27882671
TI  - Patient Perspectives: What is alopecia areata?

PMID- 27882672
TI  - Genotyping for CYP2D6 in Patients with Infantile Hemangiomas Refractory to
      Topical Timolol.

PMID- 27882674
TI  - Case Report of Focal Epithelial Hyperplasia (Heck's Disease) with Polymerase
      Chain Reaction Detection of Human Papillomavirus 13.

PMID- 27882673
TI  - Voluminous Mass within the Oral Cavity in a Healthy Newborn.

PMID- 27882675
TI  - Calibration of the TonoVet and Tono-Pen Vet tonometers in the porcine eye.
AB  - OBJECTIVE: The pig has an increasingly important role in ocular drug delivery
      models, but the most accurate tonometer in this species is unknown. The purpose
      of this study was to evaluate the accuracy of TonoVet and Tono-Pen Vet tonometers
      in the ex vivo porcine eye. PROCEDURE: Four freshly enucleated normal porcine
      eyes were cannulated with two 25-gauge needles; one connected via tubing to a
      mercury manometer calibrated continuous physiologic recorder and the other
      connected to a reservoir of lactated Ringer's solution on an adjustable stand.
      Triplicate IOP readings were taken with the TonoVet and then the Tono-Pen Vet at
      5, 10, 15, 20, 25, 30, 35, 40, 50, 60, 70, 80 mmHg. RESULTS: Linear regression
      showed strong linear trends for both the TonoVet (r2 = 0.969) and Tono-Pen Vet
      (r2 = 0.983). The TonoVet slightly underestimated IOP at lower pressures and
      slightly overestimated IOP at higher pressures (y = 1.092x - 4.0, where y =
      tonometer reading, x = manometer reading, and 4.0 = intercept). The Tono-Pen Vet
      consistently underestimated IOP (y = 0.773x - 2.1). These differences were
      statistically significant (P = <0.001, one-way repeated-measures ANOVA).
      CONCLUSION: As in other species, both the TonoVet and Tono-Pen Vet tonometers do
      not measure true IOP in the porcine eye; however, the TonoVet more closely
      approximated true IOP in the normal porcine eye than the Tono-Pen Vet and may be
      the tonometer of choice for this species.

PMID- 27882676
TI  - Highly selective coextraction of rhodamine B and dibenzyl phthalate based on high
      density dual-template imprinted shells on silica microparticles.
AB  - A simple one-pot approach based on molecularly imprinted polymer shells dispersed
      on the surface of silica for simultaneous determination of rhodamine B and
      dibenzyl phthalate (DBzP) has been developed. Highly dense molecularly imprinted
      polymer shells were formed in the mixture of acetonitrile and toluene by the
      copolymerization of methacrylic acid and ethylene glycol dimethacrylate, as well
      as two templates, rhodamine B and dibenzyl phthalate, directed by the vinyl end
      groups functional monolayer at surface silica microspheres after 3
      methacryloxypropyl trimethoxysilane modification. The obtained imprinted polymer
      shells showed large average pore diameter (102.5 nm) and about 100 nm shell
      thickness. The imprinted particles also showed high imprinting factor (alphaRhB =
      3.52 and alphaDBzP = 3.94), rapid binding kinetics, and excellent selective
      affinity capacity for rhodamine B and dibenzyl phthalate containing another three
      competitors in mixed solution. Moreover, the imprinted particles coupled with
      ultra high performance liquid chromatography was successfully applied to
      simultaneous analysis of rhodamine B and dibenzyl phthalate in two spiked
      beverage samples with average recoveries in the range of 88.0-93.0% for rhodamine
      B and 84.0-92.0% for dibenzyl phthalate with the relative standard deviation
      lower than 5.1%.

PMID- 27882677
TI  - Utility of endobronchial ultrasound-guided transbronchial needle aspiration in
      diagnosing non-specific inflammatory intrathorcacic lymphadenitis.
AB  - BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) has emerged as a minimally invasive technique for
      diagnosing intrathoracic malignancies and some benignancies; however, there are
      no data available on the utility of EBUS-TBNA for the diagnosis of non-specific
      inflammatory intrathoracic lymphadenitis. METHODS: A prospective analysis was
      performed from 104 patients with enlarged lymphadenopathy suspected of non
      specific lymphadenitis referred for EBUS-TBNA between October 2009 and March
      2012. Rapid on-site cytological evaluation was not adopted. Microbiological tests
      were carried out in all patients. Patients were excluded from the study if there
      was other diagnosis being defined. RESULTS: One hundred ninety-one lesions were
      aspirated in 94 patients with enlarged mediastinal/hilar lymph nodes within reach
      of EBUS-TBNA, which were diagnosed as non-specific intrathorcacic lymphadenitis
      by pathology and clinical follow-up. According to EBUS-TBNA pathologies, 94
      patients were categorized into four kinds: (i) inflammatory cell infiltrates
      and/or noncaseating necrosis in 38 cases; (ii) granuloma formed by epithelioid
      cells and/or fiber hyperplasia in 13 cases; (iii) lymph node tissue/lymphocyte
      without obvious abnormal lesions in 41 cases; (iv) inadequate sample in 2 cases.
      Bacterial and/or fungal smears and cultures were carried out in all 94 patients
      (100%), with pathogens being found in 4 (4.3%) cases. All patients (100%)
      underwent acid-fast staining and culture for mycobacterium tuberculosis to
      exclude tuberculosis. No procedure-related complication was observed.
      CONCLUSIONS: EBUS-TBNA can provide pathological and microbiological evidences for
      diagnosing non-specific inflammatory intrathoracic lymphadenopathy, and it is a
      safe and effective first-line investigation for ruling out malignancies and other
      benign diseases.

PMID- 27882679
TI  - Circulation of Porcine Parvovirus Types 1 through 6 in Serum Samples Obtained
      from Six Commercial Polish Pig Farms.
AB  - Porcine parvoviruses are small non-enveloped DNA viruses, very resistant to
      inactivation, and ubiquitous in the global pig population. Porcine parvovirus
      type 1 (PPV1) has been known since the 1960s and is a major causative agent of
      reproductive failure in breeding herds. During the last decade, several new
      parvoviruses have been identified in pigs by molecular methods and have been
      consecutively designated as PPV2 through PPV6. Epidemiology data for these
      viruses are limited, and the impact of these newly recognized parvoviruses on
      pigs is largely unknown. To further generate knowledge on the distribution of
      PPVs in pigs, a total of 247 serum samples were collected from six commercial
      Polish pig farms during 2013-2015 and tested by PCR assays and ELISAs. The pigs
      ranged from two to 18 weeks of age at sample collection. Breeding herds supplying
      the investigated farms were routinely vaccinated against PPV1. While all growing
      pig samples were negative for PPV1 DNA, young pigs were frequently negative for
      PPV1 antibodies and seroconversion to PPV1 was commonly seen at 9-10 weeks of
      age. The PPV2 antibody detection was highest in young pigs (2-6-week-old) and
      decreased in older pigs indicating passively acquired antibodies. The DNA
      prevalence rates in the serum samples analysed were 19% for PPV2, 7.7% for PPV3,
      2.4% for PPV4, 4.0% for PPV5 and 6.1% for PPV6. Most PPV DNA-positive samples
      were identified in 9- to 18-week-old pigs with no obvious association with
      disease on the farm. All recently emerging PPV genotypes were detected in Polish
      farms. Similar to previous reports in other pig populations, PPV2 was the most
      frequent PPV genotype circulating in Poland.

PMID- 27882680
TI  - Reconciling conceptualisations of the body and person-centred care of the older
      person with cognitive impairment in the acute care setting.
AB  - In this article, we sought reconciliation between the "body-as-representation"
      and the "body-as-experience," that is, how the body is represented in discourse
      and how the body of older people with cognitive impairment is experienced. We
      identified four contemporary "technologies" and gave examples of these to show
      how they influence how older people with cognitive impairment are often
      represented in acute care settings. We argued that these technologies may be
      mediated further by discourses of ageism and ableism which can potentiate either
      the repressive or productive tendencies of these technologies resulting in either
      positive or negative care experiences for the older person and/or their carer,
      including nurses. We then provided examples from research of embodied experiences
      of older people with dementia and of how nurses and other professionals utilized
      their inter-bodily experiences to inform acts of caring. The specificity and
      individuality of these experiences were more conducive to positive care
      experiences. We conclude the article by proposing that the act of caring is one
      way nurses seek to reconcile the "body-as-representation" with the "body-as
      experience" to mitigate the repressive effects of negative ageism and ableism.
      The act of caring, we argue, is the essence of caring enacted through the
      provision of person-centred care which evokes nurses to respond appropriately to
      the older person's "otherness," their "variation of being" while enabling them to
      enact a continuation of themselves and their own version of normality.

PMID- 27882678
TI  - A molecular transmission network of recent hepatitis C infection in people with
      and without HIV: Implications for targeted treatment strategies.
AB  - Combining phylogenetic and network methodologies has the potential to better
      inform targeted interventions to prevent and treat infectious diseases. This
      study reconstructed a molecular transmission network for people with recent
      hepatitis C virus (HCV) infection and modelled the impact of targeting directly
      acting antiviral (DAA) treatment for HCV in the network. Participants were
      selected from three Australian studies of recent HCV from 2004 to 2014. HCV
      sequence data (Core-E2) from participants at the time of recent HCV detection
      were analysed to infer a network by connecting pairs of sequences whose
      divergence was <=.03 substitutions/site. Logistic regression was used to identify
      factors associated with connectivity. Impact of targeting HCV DAAs at both HIV co
      infected and random nodes was simulated (1 million replicates). Among 236
      participants, 21% (n=49) were connected in the network. HCV/HIV co-infected
      participants (47%) were more likely to be connected compared to HCV mono-infected
      participants (16%) (OR 4.56; 95% CI; 2.13-9.74). Simulations targeting DAA HCV
      treatment to HCV/HIV co-infected individuals prevented 2.5 times more onward
      infections than providing DAAs to randomly selected individuals. Results
      demonstrate that genetic distance-based network analyses can be used to identify
      characteristics associated with HCV transmission, informing targeted prevention
      and treatment strategies.

PMID- 27882681
TI  - General practice consultations, diagnostic investigations, and prescriptions in
      the year preceding a lung cancer diagnosis.
AB  - Patterns of general practice utilization in the period before lung cancer (LC)
      diagnosis may provide new knowledge to ensure timelier and earlier diagnosis of
      LC. This study aimed to explore the prediagnostic activity in general practice in
      the year preceding LC diagnosis. The activity was compared to a matched
      comparison group. We compared LC patients with different stage, and patients with
      and without chronic obstructive pulmonary disease (COPD). Using Danish registers,
      we performed a population-based matched cohort study including lung cancer
      patients (n = 34,017) and matched comparison subjects (n = 340,170). During
      months 12 to 1 prior to diagnosis, 92.6% of LC patients and 88.4% of comparison
      subjects had one or more contacts with general practice. 13.0% of LC patients and
      3.3% of comparison subjects had two or more X-rays. 20.8% of LC patients and 8.5%
      of comparison subjects had two or more first-time antibiotics prescriptions. The
      incidence rate ratio for having a contact to general practice was similar for LC
      patients with localized disease compared to LC patients with metastatic disease.
      LC patients with COPD had more frequent contacts, lung functions tests, X-rays,
      and prescriptions than COPD patients without lung cancer, but not as pronounced
      as compared to patients without COPD. There was a significant increase in
      healthcare seeking and diagnostic activity in the year prior to a LC diagnosis,
      regardless of stage at diagnosis. COPD may mask the symptoms of LC. This
      indicates the presence of a "diagnostic time window" and a potential for more
      timely diagnosis of LC based on clinical signs and symptoms.

PMID- 27882683
TI  - Persistent Hydrogen Production by the Photo-Assisted Microbial Electrolysis Cell
      Using a p-Type Polyaniline Nanofiber Cathode.
AB  - A microbial electrolysis cell, though considered as a promising, environmentally
      friendly technology for hydrogen production, suffers from concomitant production
      of methane. The high hydrogen/methane ratio at the initial operation stage
      decreases with time. Here we report for the first time the photoassisted
      microbial electrolysis cell (MEC) for persistent hydrogen production using
      polyaniline nanofibers as a cathode. Under 0.8 V external bias and laboratory
      fluorescent light illumination in a single-chamber MEC, continuous hydrogen
      production from acetate at a rate of 1.78 mH2 3  m-3  d-1 with 79.2 % overall
      hydrogen recovery was achieved with negligible methane formation for six months.
      Energy efficiencies based on input electricity as well as input electricity plus
      substrate were 182 and 66.2 %, respectively. This was attributed to the p-type
      semiconductor characteristics of polyaniline nanofibers in which photoexcited
      electrons are used to reduce protons at the surface and holes are reduced with
      electrons originating from acetate oxidation at the anode. This method can be
      extended to microbial wastewater treatment for hydrogen production.

PMID- 27882684
TI  - Transformation of Cellulose into Nonionic Surfactants Using a One-Pot Catalytic
      Process.
AB  - Alkyl glucosides surfactants are synthesized by a cascade process that involves
      the methanolysis of cellulose into methyl glucosides followed by the
      transacetalization with n-octanol. The first step was performed using methanol as
      solvent and acid catalysts (such as, inorganic acids, heteropolyacids,
      ionexchange resins, or modified carbon materials). Subsequently, long-chain alkyl
      glucosides are obtained in the second step by transacetalization, which involves
      the reaction of methyl glucosides with a fatty alcohol using the same acid
      catalyst. The overall process was performed under mild conditions. Amorphous
      sulfonated carbon catalyst achieved the best results for the complete conversion
      of cellulose in methanol at 200  degrees C with methyl alpha,beta
      glucopyranosides yields higher than 80 %. Moreover, this material containing -SO3
      H groups is ideal to perform the second step to obtain octyl and decyl glucosides
      in yields higher than 73 % at 120  degrees C. In addition, the sulfonated carbon
      catalyst (C-SO3 H) can be reused with only a slightly decrease of its activity
      after four consecutive cycles.

PMID- 27882682
TI  - Prevalence of Equine Hepacivirus Infections in France and Evidence for Two Viral
      Subtypes Circulating Worldwide.
AB  - Like hepatitis C virus (HCV) in humans, the newly identified equine hepacivirus
      (NPHV) displays a predominating liver tropism that may evolve into chronic
      infections. The genomes of the two viruses share several organizational and
      functional features and are phylogenetically closest amongst the Hepacivirus
      genus. A limited amount of data is available regarding the spread of hepacivirus
      infections in horses. In this study, we asked whether in a more representative
      sample the prevalence and distribution of NPHV infections in France would
      resemble that reported so far in other countries. A total of 1033 horses sera
      from stud farms throughout France were analysed by qRT-PCR to determine the
      prevalence of ongoing NPHV infections and viral loads; in positive samples,
      partial sequences of NPHV's genome (5'UTR, NS3 and NS5B genes) were determined.
      Serum concentrations of biliary acids, glutamate dehydrogenase (GLDH) and L-gamma
      glutamyl transferase (gamma-GT) were measured for most horses. We detected NPHV
      infections in 6.2% of the horses, a prevalence that reached 8.3% in thoroughbreds
      and was significantly higher than in other breeds. The presence of circulating
      virus was neither significantly associated with biological disturbances nor with
      clinical hepatic impairment. Our phylogenetic analysis was based on both
      neighbour-joining and maximum-likelihood approaches. Its result shows that, like
      almost everywhere else in the world so far, two major groups of NPHV strains
      infect French domestic horses. Based on genetic distances, we propose a
      classification into two separate NPHV subtypes. Viral loads in the serum of
      horses infected by the main subtype were, in average, four times higher than in
      those infected by the second subtype. We hypothesize that amino acid
      substitutions in the palm domain of NS5B between NPHV subtypes could underlie
      viral phenotypes that explain this result.

PMID- 27882685
TI  - Elective ambulatory blood pressure monitoring to diagnose masked hypertension
      after kidney transplantation: are we ready for that?

PMID- 27882686
TI  - Ensuring adequate immunizations among pediatric liver transplant recipients: A
      team approach.

PMID- 27882687
TI  - Pediatric organ donation rates-going beyond registry data.

PMID- 27882688
TI  - Changing expectations for Fontan patient survival after heart transplantation.

PMID- 27882689
TI  - Is a reduction in cystometric bladder capacity in anuric infants post-renal
      transplant really no big deal?

PMID- 27882690
TI  - The complexities of homozygous familial hypercholesterolemia management.

PMID- 27882691
TI  - Image-guided fine-needle aspiration cytology and flow cytometry phenotyping of
      neck lymphadenopathy for the diagnosis of recurrent lymphoma.
AB  - OBJECTIVE: In patients with a history of lymphoma, each lymphadenopathy should be
      carefully evaluated. The aims of this study were to evaluate (i) the usefulness
      of high-resolution ultrasonography (US), US-guided fine-needle aspiration
      cytology (FNAC) and flow cytometry phenotyping (FCP) together in the diagnosis of
      recurrent lymphoma and (ii) whether these tools were independent predictors of
      correct results. DESIGN: Retrospective cohort study with stepwise forward
      logistic regression analysis of results. SETTING: Tertiary referral centre.
      PARTICIPANTS: A total of 151 patients with a history of lymphoma who developed a
      cervical mass during follow-up. METHODS: On neck US, a lymphadenopathy was shown
      in 129 (85.4%) patients (median age 57 years, range 18-78 years), and US-guided
      FNAC combined with FCP were immediately performed. All patients had surgical
      excision and subsequent histological examination of the enlarged node(s), to
      establish lymphoma subclassification. RESULTS: Final histology confirmed
      recurrence in 82 (63.6%) patients. According to the logistic regression analysis,
      FNAC and FCP were independent predictors of correct results (P = 0.009 and 0.028,
      respectively) and did not interfere with each other. The sensitivity, specificity
      and accuracy of the combination of all of the tools were 98.8%, 100% and 99.2%,
      respectively, and the area under the receiver operating characteristic curve was
      0.902 (95% CI: 0.797-0.986). CONCLUSION: This minimally invasive procedure is
      easily performed and should be recommended for all patients with cervical
      lymphadenopathy and a history of lymphoma, avoiding the need of core-biopsy or
      surgical excision if recurrence was excluded.

PMID- 27882692
TI  - Current progress on microRNAs-based therapeutics in neurodegenerative diseases.
AB  - MicroRNAs (miRNAs)-based therapy has recently emerged as a promising strategy in
      the treatments of neurodegenerative diseases. Thus, in this review, the most
      recent and important challenges and advances on the development of miRNA
      therapeutics for brain targeting are discussed. In particular, this review
      highlights current knowledge and progress in the field of manufacturing,
      recovery, isolation, purification, and analysis of these therapeutic
      oligonucleotides. Finally, the available miRNA delivery systems are reviewed and
      an analysis is presented in what concerns to the current challenges that have to
      be addressed to ensure their specificity and efficacy. Overall, it is intended to
      provide a perspective on the future of miRNA-based therapeutics, focusing the
      biotechnological approach to obtain miRNAs. WIREs RNA 2017, 8:e1409. doi:
      10.1002/wrna.1409 For further resources related to this article, please visit the
      WIREs website.

PMID- 27882694
TI  - Fused Bicyclic Caspase-1 Inhibitors Assembled by Copper-Free Strain-Promoted
      Alkyne-Azide Cycloaddition (SPAAC).
AB  - Challenges exist in the development of potent and selective small-molecule
      inhibitors against caspase-1. Herein, by making use of the copper-free strain
      promoted alkyne-azide cycloaddition (SPAAC) reaction between difluorinated
      cyclooctynes (DIFOs) and various azide-containing compounds, we showed for the
      first time that potential caspase-1 inhibitors could be rapidly synthesized. The
      resulting fused bicyclic compounds structurally resembled the central portion (P2
      -P3 ) of Pralnacasan (a well-known small molecule caspase-1 inhibitor), with
      diversity at the P4 -position of the parental inhibitor conveniently installed
      from the azide component. Since our SPAAC-assembled inhibitor library was
      synthesized by using a copper-free bioorthogonal chemistry, the resulting 52
      membered library (2 DIFOs*26 azides) was immediately ready for subsequent cell
      based screening for rapid identification of potential cell-permeable hits capable
      of effectively inhibiting endogenous caspase-1 activities. C1FS, a recently
      reported fluorogenic two-photon probe, which possesses improved live-cell imaging
      sensitivity against endogenous caspase-1, was used both in vitro and in LPS/ATP
      induced macrophages (a well-established caspase-1-activated cell model) to screen
      against selected compounds from the above-mentioned library, leading to
      subsequent discovery of a novel caspase-1 inhibitor named b7-b.

PMID- 27882693
TI  - Direct Transformation of HMF into 2,5-Diformylfuran and 2,5-Dihydroxymethylfuran
      without an External Oxidant or Reductant.
AB  - The selective transformation of 5-hydroxymethylfurfural (HMF) to valuable 2,5
      diformylfuran (DFF) and 2,5-dihydroxymethylfuran (DHMF) is highly desirable but
      remains a great challenge owing to its tendency to over-oxidation and over
      reduction. In this work, HMF is directly converted into DFF and DHMF without
      external oxidant or reductant through a Meerwein-Ponndorf-Verley-Oppenauer (MPVO)
      reaction. In such a MPVO process, HMF is used as both oxidant and reductant and
      DFF and DHMF are simultaneously produced with a 1:1 molar ratio in the presence
      of a Lewis acid catalyst. Under high initial HMF concentration, a HMF conversion
      of up to 44.7 % can be reached within 1 h. Moreover, this atom-efficient
      transformation route for HMF also provides a promising protocol for the crude
      separation of DHMF products from DFF products, owing to the lower solubility of
      DHMF compared to DFF in acetonitrile.

PMID- 27882695
TI  - Effects of polyethylene glycol and a synthetic ice blocker during vitrification
      of immature porcine oocytes on survival and subsequent embryo development.
AB  - We evaluated the effects of polyethylene glycol (PEG) and Supercool X-1000 (SC)
      as supplements during the vitrification of immature cumulus-enclosed porcine
      oocytes in a solution based on 17.5% ethylene glycol + 17.5% propylene glycol.
      After warming, the oocytes were subjected to in vitro maturation, fertilization
      and embryo culture. In Experiment 1, equilibration and vitrification solutions
      were supplemented with or without 2% (w/v) PEG (PEG+ and PEG-, respectively). The
      survival rate, cleavage and blastocyst development were similar between PEG+ and
      PEG- groups; however, all values were lower than those in the non-vitrified
      control. In Experiment 2, vitrification solution was supplemented with or without
      1% (v/v) SC (SC+ and SC-, respectively). The percentages of survival and
      blastocyst development were similar between SC+ and SC- groups but lower than
      those in the non-vitrified control. The percentage of cleavage in the SC- group
      was significantly lower than the control and the SC+ groups, which were in turn
      similar to one another. In both experiments, the cell numbers in blastocysts were
      not significantly different among the non-vitrified and vitrified groups. In
      conclusion, PEG did not improve oocyte survival and embryo development, whereas
      SC improved the ability of surviving oocytes to cleave but not to develop into
      blastocysts.

PMID- 27882697
TI  - Biomechanical properties of an implanted engineered tubular gut-sphincter
      complex.
AB  - Neuromuscular diseases of the gut alter the normal motility patterns. Although
      surgical intervention remains the standard treatment, preservation of the
      sphincter attached to the rest of the gut is challenging. The present study aimed
      to evaluate a bioengineered gut-sphincter complex following its subcutaneous
      implantation for 4 weeks in rats. Engineered innervated human smooth muscle
      sheets and innervated human sphincters with a predefined alignment were placed
      around tubular scaffolds to create a gut-sphincter complex. The engineered
      complex was subcutaneously implanted in the abdomen of the rats for 4 weeks. The
      implanted tissues were vascularized. In vivo manometry revealed luminal pressure
      at the gut and the sphincter zone. Tensile strength, elongation at break and
      Young's modulus of the engineered complexes were similar to those of native rat
      intestine. Histological and immunofluorescence assays showed maintenance of
      smooth muscle circular alignment in the engineered tissue, maintenance of smooth
      muscle contractile phenotype and innervation of the smooth muscle. Electrical
      field stimulation induced relaxation of the smooth muscle of both the sphincter
      and the gut parts. Relaxation was partly inhibited by nitric oxide inhibitor
      indicating nitrergic contribution to relaxation. The present study has
      demonstrated for the first time a successfully developed and subcutaneously
      implanted a tubular human-derived gut-sphincter complex. The sphincteric part of
      Tubular Gut-Sphincter Complex (TGSC) maintained the basal tone characteristic of
      a native sphincter. The gut part also maintained its specific neuromuscular
      characteristics. The results of this study provide a promising therapeutic
      approach to restore gut continuity and motility. Copyright (c) 2016 John Wiley &
      Sons, Ltd.

PMID- 27882698
TI  - The cellular and molecular basis of cnidarian neurogenesis.
AB  - Neurogenesis initiates during early development and it continues through later
      developmental stages and in adult animals to enable expansion, remodeling, and
      homeostasis of the nervous system. The generation of nerve cells has been
      analyzed in detail in few bilaterian model organisms, leaving open many questions
      about the evolution of this process. As the sister group to bilaterians,
      cnidarians occupy an informative phylogenetic position to address the early
      evolution of cellular and molecular aspects of neurogenesis and to understand
      common principles of neural development. Here we review studies in several
      cnidarian model systems that have revealed significant similarities and
      interesting differences compared to neurogenesis in bilaterian species, and
      between different cnidarian taxa. Cnidarian neurogenesis is currently best
      understood in the sea anemone Nematostella vectensis, where it includes
      epithelial neural progenitor cells that express transcription factors of the soxB
      and atonal families. Notch signaling regulates the number of these neural
      progenitor cells, achaete-scute and dmrt genes are required for their further
      development and Wnt and BMP signaling appear to be involved in the patterning of
      the nervous system. In contrast to many vertebrates and Drosophila, cnidarians
      have a high capacity to generate neurons throughout their lifetime and during
      regeneration. Utilizing this feature of cnidarian biology will likely allow
      gaining new insights into the similarities and differences of embryonic and
      regenerative neurogenesis. The use of different cnidarian model systems and their
      expanding experimental toolkits will thus continue to provide a better
      understanding of evolutionary and developmental aspects of nervous system
      formation. WIREs Dev Biol 2017, 6:e257. doi: 10.1002/wdev.257 For further
      resources related to this article, please visit the WIREs website.

PMID- 27882696
TI  - Fetuin-A (alpha 2HS glycoprotein) modulates growth, motility, invasion, and
      senescence in high-grade astrocytomas.
AB  - Glioblastomas (high-grade astrocytomas) are highly aggressive brain tumors with
      poor prognosis and limited treatment options. In the present studies, we have
      defined the role of fetuin-A, a liver-derived multifunctional serum protein, in
      the growth of an established glioblastoma cell line, LN229. We hereby demonstrate
      that these cells synthesize ectopic fetuin-A which supports their growth in
      culture in the absence of serum. We have demonstrated that a panel of tissue
      microarray (TMA) of glioblastomas also express ectopic fetuin-A. Knocking down
      fetuin-A using shRNA approach in LN229, significantly reduced their in vitro
      growth as well as growth and invasion in vivo. The fetuin-A knockdown subclones
      of LN229 (A and D) also had reduced motility and invasive capacity. Treatment of
      LN229 cells with asialofetuin (ASF), attenuated their uptake of labeled fetuin-A,
      and induced senescence in them. Interestingly, the D subclone that had ~90%
      reduction in ectopic fetuin-A, underwent senescence in serum-free medium which
      was blunted in the presence of purified fetuin-A. Uptake of labeled exosomes was
      attenuated in fetuin-A knockdown subclones A and D. Taken together, the studies
      demonstrate the impact of fetuin-A as significant node of growth, motility, and
      invasion signaling in glioblastomas that can be targeted for therapy.

PMID- 27882699
TI  - Controlled Retention and Release of Biomolecular Transport Systems Using Shape
      Changing Polymer Bilayers.
AB  - Biomolecular transport systems based on cytoskeletal filaments and motor proteins
      have become promising tools for a wide range of nanotechnological applications.
      In this paper, we report control of such transport systems using substrates with
      switchable shape. We demonstrate this approach on the example of microtubules
      gliding on surfaces of self-folding polymer bilayers with adsorbed kinesin
      motors. The polymer bilayers are able to undergo reversible transitions between
      flat and tube-like shapes that allow the externally controlled retention and
      release of gliding microtubules. The demonstrated approach, based on surfaces
      with reconfigurable topography, opens broad perspectives to control biomolecular
      transport systems for bioanalytical and sensing applications, as well as for the
      construction of subcellular compartments in the field of synthetic biology.

PMID- 27882700
TI  - Effects of lapatinib or trastuzumab, alone and in combination, in human epidermal
      growth factor receptor 2-positive breast cancer: a meta-analysis of randomized
      controlled trials.
AB  - This meta-analysis compared the efficiency and safety of lapatinib and
      trastuzumab, alone or in combination, administered with neoadjuvant chemotherapy
      in patients with human epidermal growth factor receptor 2 (HER2)-positive breast
      cancer. For dichotomous variables, the relative risk ratio (RR) and 95%
      confidence interval (CI) were used to investigate outcome measures: pathological
      complete response (pCR), neutropenia, diarrhea, dermatologic toxicity, and
      congestive heart failure (CHF). Eight randomized controlled trials of 2350
      participants (837 receiving lapatinib, 913 trastuzumab, and 555 combination
      therapy) were selected to compare the efficiency and safety of lapatinib to
      trastuzumab. A significant difference was found between lapatinib and trastuzumab
      for pCR (RR = 0.82, 95% CI: 0.73-0.93; Z = 3.00; P = 0.003). In six studies, a
      significant difference was found between trastuzumab and combination therapy for
      pCR (RR = 1.33, 95% CI: 1.18-1.50; Z = 4.70; P < 0.00001), diarrhea (RR = 14.59,
      95% CI: 7.69-27.67; Z = 8.20; P < 0.00001), and dermatologic toxicity (RR = 3.10,
      95% CI: 1.61-5.96; Z = 3.39; P = 0.007), but none was found for neutropenia (RR =
      1.38, 95% CI: 0.82-2.31; Z = 1.22; P = 0.22) or CHF (RR = 0.14, 95% CI: 0.02
      1.17; Z = 1.02; P = 0.07). Combination therapy compared to trastuzumab alone
      increases the pCR rate of HER2-positive breast cancer patients with no additional
      cardiac events. Trastuzumab, which is still the first-line therapy in breast
      cancer, increases the pCR rate more than lapatinib.

PMID- 27882701
TI  - Landscape-scale spatial abundance distributions discriminate core from random
      components of boreal lake bacterioplankton.
AB  - Aquatic bacterial communities harbour thousands of coexisting taxa. To meet the
      challenge of discriminating between a 'core' and a sporadically occurring
      'random' component of these communities, we explored the spatial abundance
      distribution of individual bacterioplankton taxa across 198 boreal lakes and
      their associated fluvial networks (188 rivers). We found that all taxa could be
      grouped into four distinct categories based on model statistical distributions
      (normal like, bimodal, logistic and lognormal). The distribution patterns across
      lakes and their associated river networks showed that lake communities are
      composed of a core of taxa whose distribution appears to be linked to in-lake
      environmental sorting (normal-like and bimodal categories), and a large fraction
      of mostly rare bacteria (94% of all taxa) whose presence appears to be largely
      random and linked to downstream transport in aquatic networks (logistic and
      lognormal categories). These rare taxa are thus likely to reflect species sorting
      at upstream locations, providing a perspective of the conditions prevailing in
      entire aquatic networks rather than only in lakes.

PMID- 27882702
TI  - Frequency-dependent selection for rare genotypes promotes genetic diversity of a
      tropical palm.
AB  - Negative frequency-dependent selection among species is a key driver of community
      diversity in natural systems, but the degree to which negative frequency
      dependent selection shapes patterns of survival and genetic diversity within
      species is poorly understood. In a 5-year field experiment, we show that
      seedlings of a tropical palm with rare genotypes had a pronounced survival
      advantage over seedlings with common genotypes, with effect sizes comparable to
      that of light availability. This 'rare genotype advantage' led to an increase in
      population-wide genetic diversity among seedlings compared to null expectations,
      as predicted by negative frequency-dependent selection, and increased
      reproductive success in adult trees with rare genotypes. These results suggest
      that within-species negative frequency-dependent selection of genotypes can shape
      genetic variation on ecologically relevant timescales in natural systems and may
      be a key, overlooked source of non-random mortality for tropical plants.

PMID- 27882703
TI  - Species pools, community completeness and invasion: disentangling diversity
      effects on the establishment of native and alien species.
AB  - Invasion should decline with species richness, yet the relationship is
      inconsistent. Species richness, however, is a product of species pool size and
      biotic filtering. Invasion may increase with richness if large species pools
      represent weaker environmental filters. Measuring species pool size and the
      proportion realised locally (completeness) may clarify diversity-invasion
      relationships by separating environmental and biotic effects, especially if
      species' life-history stage and origin are accounted for. To test these
      relationships, we added seeds and transplants of 15 native and alien species into
      29 grasslands. Species pool size and completeness explained more variation in
      invasion than richness alone. Although results varied between native and alien
      species, seed establishment and biotic resistance to transplants increased with
      species pool size, whereas transplant growth and biotic resistance to seeds
      increased with completeness. Consequently, species pools and completeness
      represent multiple independent processes affecting invasion; accounting for these
      processes improves our understanding of invasion.

PMID- 27882704
TI  - Evolutionary consequences of ecological factors: pollinator reliability predicts
      mating-system traits of a perennial plant.
AB  - The reproductive-assurance hypothesis predicts that mating-system traits will
      evolve towards increased autonomous self-pollination in plant populations
      experiencing unreliable pollinator service. We tested this long-standing
      hypothesis by assessing geographic covariation among pollinator reliability,
      outcrossing rates, heterozygosity and relevant floral traits across populations
      of Dalechampia scandens in Costa Rica. Mean outcrossing rates ranged from 0.16 to
      0.49 across four populations, and covaried with the average rates of pollen
      arrival on stigmas, a measure of pollinator reliability. Across populations,
      genetically based differences in herkogamy (anther-stigma distance) were
      associated with variation in stigmatic pollen loads, outcrossing rates and
      heterozygosity. These observations are consistent with the hypothesis that, when
      pollinators are unreliable, floral traits promoting autonomous selfing evolve as
      a mechanism of reproductive assurance. Extensive covariation between floral
      traits and mating system among closely related populations further suggests that
      floral traits influencing mating systems track variation in adaptive optima
      generated by variation in pollinator reliability.

PMID- 27882705
TI  - Erratum for Arguello et al. (2016).

PMID- 27882707
TI  - A ripple effect: Reshaping culture through gerontological nursing.

PMID- 27882706
TI  - High frequency of potential interactions between direct-acting antivirals and
      concomitant therapy in HIV/hepatitis C virus-coinfected patients in clinical
      practice.
AB  - OBJECTIVES: The aim of the study was to analyse the frequency and degree of
      potential drug-drug interactions (DDIs) between direct-acting antivirals (DAAs)
      and concomitant medication used by HIV/hepatitis C virus (HCV)-coinfected
      patients, including antiretroviral therapy (ART) and other drugs. METHODS: All
      patients with HIV infection and viraemic HCV genotype 1, 3 or 4 coinfection
      attending a tertiary care centre in Spain (November 2014 to November 2015) were
      included in the study. DDIs were classified as major, i.e. drugs should not be co
      administered, or minor, i.e. close monitoring, dosage alteration or change in
      timing may be required if drugs are co-administered, following the http://www.hep
      druginteractions.org database recommendations. RESULTS: A total of 244 patients
      were included in the study, of whom 224 (92%) were previous injecting drug users.
      Major DDIs were found for: paritaprevir-r/ombitasvir plus dasabuvir (3D), in 60
      (44%) of 138 individuals with genotype 1; paritaprevir-r/ombitasvir (2D), in 22
      (37%) of 60 individuals with genotype 4; sofosbuvir/ledipasvir (SOF/LDV), in four
      (2%) of 198 patients with genotype 1 or 4; simeprevir (SMV) plus SOF, in 160
      (81%) of 198 patients with genotype 1 or 4; daclatasvir (DCV) plus SOF, in seven
      (3%) of 244 patients with genotype 1, 3 or 4 (P < 0.001). Minor DDIs were found
      for: 3D, in 123 (89%) individuals with genotype 1; 2D, in 52 (87%) individuals
      with genotype 4; SOF/LDV, in 154 (78%) patients with genotype 1 or 4; SMV plus
      SOF, in 129 (65%) patients with genotype 1 or 4; DCV plus SOF, in 149 (61%)
      patients with genotype 1, 3 or 4 (P < 0.001). CONCLUSIONS: Drug-drug interactions
      between DAAs and ART or other commonly prescribed medications are frequently
      found among HIV/HCV-coinfected patients. Potential major and minor DDIs are more
      frequent with 3D, 2D and SMV plus SOF regimens.

PMID- 27882708
TI  - OBITUARY to Professor Jan Reed former editor IJOPN.

PMID- 27882709
TI  - Using a tracheal stent for conservative management of speaking valve-associated
      tracheo-oesophageal fistula.

PMID- 27882710
TI  - John Porter Book Prize Lecture: Bringing the Social Back In-On the Integration of
      Muslim Immigrants and the Jurisprudence of Muslim Minorities.
AB  - In much of the academic debate on the integration of Muslims into Western liberal
      democracies, Islam is often treated as one or the sole independent variable in
      the lives of Muslims. Offering to view Islam-or the understanding of Islam among
      Muslims-as the dependent variable, The Muslim Question in Canada discusses the
      influence of socioeconomic forces in shaping the Muslim immigrants' opinions,
      modes of thinking, and even interpretations of their faith. Drawing on this
      general approach, which is introduced and developed in the book using a variety
      of both quantitative and qualitative data, this article focuses on a school of
      thought within the Islamic jurisprudence known as fiqh al-aqalliyyat al-Muslema
      (the jurisprudence of Muslim minorities). The premise of the jurisprudence of
      Muslim minorities is that the lived realities of Muslims who reside in non-Muslim
      countries are so fundamentally different from those of the Muslim-majority
      nations that traditional Islamic jurisprudence cannot offer meaningful solutions
      for their problems. Therefore, there is a need to establish an entirely different
      jurisprudential approach centered around the lives of the Muslim minorities. The
      purpose of the bulk of jurisprudential theorization efforts in this line of
      reasoning is to facilitate the lives of the Muslim minorities; as well, they aim
      to create a foundation for the moral obligations of Muslims toward non-Muslims in
      such environments. I argue that a crucial element that triggers such a
      development is the existence of a positive relationship between Muslims and non
      Muslims in immigrant-receiving countries. Souvent au sein des debats sur
      l'integration des Musulmans dans des democraties liberales de l'Ouest, l'Islam
      est traite comme un ou le seul enjeu dans la vie des fideles. The Muslim Question
      in Canada examine l'Islam ou la comprehension de l'Islam chez les Musulmans comme
      un enjeu dependent et aborde l'influence des forces socio-economiques sur les
      opinons des immigrants musulmans ainsi que sur leurs modes de pensee et meme sur
      la maniere dont ils interpretent leur foi. Inspire par cette approche, que l'on
      presente et developpe dans le livre, et qui se sert de donnees a la fois
      quantitatives et qualitatives, cet article se concentre sur une ecole de pensee a
      l'interieur de la jurisprudence islamique, connue sous le nom de fiqh al
      aqalliyyat al-Muslema (la jurisprudence des minorites musulmanes). La premisse de
      la jurisprudence des minorites musulmanes est que les realites vecues par les
      Musulmans qui vivent dans des pays non-musulmans sont au fond tellement
      differentes de celles de la majorite musulmane que la jurisprudence
      traditionnelle ne presente pas de solutions pertinentes pour resoudre leurs
      problemes. Ainsi, il faut etablir une approche jurisprudentielle totalement
      differente, axee sur la vie des minorites musulmanes. L'objectif de la plupart
      des efforts au niveau de la theorisation de la jurisprudence qui adoptent cette
      vision est de rendre la vie des minorites musulmanes plus facile. Ces efforts
      tentent aussi de faire en sorte que les Musulmans ressentent une certaine
      obligation morale envers les non-Musulmans dans ces environnements. J'avance ici
      que l'aspect qui declenche un tel developpement est le rapport positif entre les
      Musulmans et les non-Musulmans dans les pays qui recoivent des immigrants.

PMID- 27882711
TI  - Reconciliation in the Context of Settler-Colonial Gender Violence: "How Do We
      Reconcile with an Abuser?"

PMID- 27882712
TI  - In Memoriam: Thelma McCormack 1921 to 2016 Professor Emerita, Sociology, York.

PMID- 27882713
TI  - CRS Symposium on Reconciling Indigenous-Settler Relations in Canada: Whose Voice
      Counts?

PMID- 27882715
TI  - Factors Influencing Church Choice: An Exploration of Responses from New Attendees
      at Growing Canadian Mainline Churches.
AB  - Seventy new attendees of growing Mainline Protestant churches in Canada agreed to
      be interviewed regarding what attracted them to, and kept them at, their current
      congregation. A variety of responses revealed that, in part, the new attendees
      were drawn to their Mainline Protestant church by aspects of Conservative
      Protestant theology. Contemporary theories of group membership are used to
      explore the links between Conservative Protestant theology, group cohesion, and,
      to a lesser extent, church growth. Soixante-dix nouveaux participants provenant
      d'une eglise protestante traditionnelle au Canada en croissance ont accepte
      d'etre interviewes au sujet des caracteristiques qui les ont attires et qui les
      ont gardes a leur congregation actuelle. Une variete de reponses a demontre que,
      en partie, les nouveaux participants ont ete attires par leur eglise protestante
      traditionnelle par les aspects de la theologie protestante conservatrice. Les
      theories contemporaines de l'appartenance au groupe sont utilisees pour explorer
      les liens entre la theologie protestante conservatrice, la cohesion du groupe, et
      dans une moindre mesure, la croissance de l'eglise.

PMID- 27882716
TI  - Toward a Sociology of the Reconciliation of Conflicting Desires.
AB  - Desire-based research provides people and communities the opportunity to share
      their dreams and hopes for a better future. However, conflicting desires are
      difficult to reconcile. We suggest that sociological research to understand
      conflicting desires is required to support reconciliation work by Indigenous and
      non-Indigenous people in Canada. Our contribution begins by identifying much of
      current and past sociological research about Indigenous people and communities as
      damaged-centered, that is, identifying problems and obstacles in the hope that
      the knowledge will lead to change. This model of social change is flawed. We
      believe that most Canadians desire justice for Indigenous peoples while at the
      same time desiring land and access to resources, desires that deny that justice.
      How we as a society reconcile these desires will determine the extent to which
      true justice for Indigenous peoples will be achieved. We propose a sociology of
      the reconciliation of conflicting desires and suggest some practical ways that
      this type of research could move forward.

PMID- 27882717
TI  - Is it Homophobia or Homoppression?

PMID- 27882719
TI  - Mediating the Space Between: Voices of Indigenous Youth and Voices of Educators
      in Service of Reconciliation.

PMID- 27882718
TI  - Catching Up or Falling Behind? Continuing Wealth Disparities for Immigrants to
      Canada by Region of Origin and Cohort.
AB  - This paper investigates wealth disparities among first-generation immigrants
      using data from the 2012 Survey of Financial Security. We apply logistic and
      linear regression models to estimate disparities in homeownership and household
      equivalent net worth by immigrant status, region of origin, and time since
      arrival. By focusing on immigrant families from different regions who entered
      Canada at different points in time, this research applies theories related to
      assimilation, human capital, and structural barriers to wealth. Our findings
      demonstrate that even though many immigrant families transition into
      homeownership and grow their wealth over time, certain first-generation immigrant
      groups continue to experience wealth disparities many years after their arrival
      to Canada. In particular, immigrant families from African, Asian, and Middle
      Eastern countries experienced the largest wealth gaps. Cet article examine les
      disparites de richesse entre les immigrants de premiere generation en utilisant
      les donnees de l'Enquete 2012 sur la securite financiere. Nous appliquons des
      modeles de regression logistique et lineaire pour estimer les disparites dans la
      propriete et valeur nette des menages equivalente par le statut d'immigrant, la
      region d'origine, et le temps ecoule depuis leur arrivee. En se concentrant sur
      les familles d'immigrants de differentes regions qui sont entres au Canada a
      differents points dans le temps, cette recherche applique les theories liees a
      l'assimilation, le capital humain, et les obstacles structurels a la richesse.
      Nos resultats demontrent que meme si de nombreuses familles d'immigrants
      transition vers la propriete et de croitre leur richesse au fil du temps,
      certains groupes d'immigrants de premiere generation continuent d'eprouver des
      disparites de richesse de nombreuses annees apres leur arrivee au Canada. En
      particulier, les familles d'immigrants d'Afrique, d'Asie, et les pays du Moyen
      Orient ont connu les plus grands ecarts de richesse.

PMID- 27882720
TI  - Using Our Good Minds to Foster Reconciliation: A Story of Optimism.

PMID- 27882723
TI  - An In-Depth Understanding of Biomass Recalcitrance Using Natural Poplar Variants
      as the Feedstock.
AB  - In an effort to better understand the biomass recalcitrance, six natural poplar
      variants were selected as feedstocks based on previous sugar release analysis.
      Compositional analysis and physicochemical characterizations of these poplars
      were performed and the correlations between these physicochemical properties and
      enzymatic hydrolysis yield were investigated. Gel permeation chromatography (GPC)
      and 13 C  solid state NMR were used to determine the degree of polymerization
      (DP) and crystallinity index (CrI) of cellulose, and the results along with the
      sugar release study indicated that cellulose DP likely played a more important
      role in enzymatic hydrolysis. Simons' stain revealed that the accessible surface
      area of substrate significantly varied among these variants from 17.3 to 33.2 mg
      g-1biomass as reflected by dye adsorption, and cellulose accessibility was shown
      as one of the major factors governing substrates digestibility. HSQC and 31 P NMR
      analysis detailed the structural features of poplar lignin variants. Overall,
      cellulose relevant factors appeared to have a stronger correlation with glucose
      release, if any, than lignin structural features. Lignin structural features,
      such as a phenolic hydroxyl group and the ratio of syringyl and guaiacyl (S/G),
      were found to have a more convincing impact on xylose release. Low lignin
      content, low cellulose DP, and high cellulose accessibility generally favor
      enzymatic hydrolysis; however, recalcitrance cannot be simply judged on any
      single substrate factor.

PMID- 27882722
TI  - Designed inhibitor for nuclear localization signal of polo-like kinase 1 induces
      mitotic arrest.
AB  - Polo-like kinase 1 (Plk1), a member of polo-like kinase family, regulates
      multiple essential steps of the cell cycle progression. Plk1 is overexpressed in
      multiple cancer cell lines and considered to be a prime anticancer target. Plk1
      accumulates in the nucleus during S and G2 phases by its bipartite nuclear
      localization signal (NLS) sequence, which is crucial for Plk1 regulation during
      normal cell cycle progression. Here, through combined computational and
      experimental studies, we identified compound D110, which inhibits Plk1 kinase
      activity with an IC50 of 85 nm and blocks the nuclear localization of Plk1 during
      S and G2 phases. D110-treated cancer cells were arrested at mitosis with
      monopolar spindle, indicating the inhibition of the Plk1 kinase activity in cell.
      As D110 interacts with both the ATP site and the NLS in Plk1, it demonstrates
      good selectivity toward Plk2 and Plk3. The strategy of simultaneously inhibiting
      kinase activity and its subcellular translocations offers a novel approach for
      selective kinase inhibitor design.

PMID- 27882721
TI  - Survival of patients with metastatic leiomyosarcoma: the MD Anderson Clinical
      Center for targeted therapy experience.
AB  - Advanced stage leiomyosarcoma (LMS) is incurable with current systemic antitumor
      therapies. Therefore, there is clinical interest in exploring novel therapeutic
      regimens to treat LMS. We reviewed the medical records of 75 consecutive patients
      with histologically confirmed metastatic LMS, who had been referred to the
      Clinical Center for Targeted Therapy at MD Anderson Cancer Center. To lay the
      foundation for potential phase I trials for the treatment of advanced LMS, we
      analyzed tumor response and survival outcome data. The frequent hotspot gene
      aberrations that we observed were the TP53 mutation (65%) and RB1 loss/mutation
      (45%) detected by Sequenom or next-generation sequencing. Among patients treated
      with gene aberration-related phase I trial therapy, the median progression-free
      survival was 5.8 months and the median overall survival was 15.9 months,
      significantly better than in patients without therapy (1.9 months, P = 0.001; and
      8.7 months, P = 0.013, respectively). Independent risk factors that predicted
      shorter overall survival included hemoglobin <10 g/dL, body mass index <30 kg/m2
      , serum albumin <3.5 g/dL, and neutrophil above upper limit of normal. The median
      survivals were 19.9, 7.6, and 0.9 months for patients with 0, 1 or 2, and >=3 of
      the above risk factors, respectively (P < 0.001). A prognostic scoring system
      that included four independent risk factors might predict survival in patients
      with metastatic LMS who were treated in a phase I trial. Gene aberration-related
      therapies led to significantly better clinical benefits, supporting that further
      exploration with novel mechanism-driven therapeutic regimens is warranted.

PMID- 27882724
TI  - Efficacy and safety of darbepoetin alfa initiated at hemoglobin <=10 g/dL in
      patients with stage IV cancer and chemotherapy-induced anemia.
AB  - Data on efficacy and safety of darbepoetin alfa (DA) administered at hemoglobin
      (Hb) <=10 g/dL are limited. In this analysis, we examined DA's efficacy and
      safety in patients with Stage IV cancers and chemotherapy-induced anemia (CIA)
      initiated on DA at Hb <=10 g/dL. Data for patients with Stage IV cancers and CIA
      and who initiated DA at Hb <=10 g/dL were extracted from three phase 3 trials
      identified in a central database of Amgen-sponsored DA studies in CIA. Efficacy
      outcomes were assessed by achievement of Hb increases of >=1 g/dL and >=2 g/dL
      and red blood cell (RBC) or whole blood transfusion requirements. Data were
      analyzed for all patients with baseline Hb <=10 g/dL, and by the subgroups of
      patients with baseline Hb >=9 to <=10 g/dL versus <9 g/dL. Crude and Kaplan-Meier
      proportions of patients who experienced each outcome and time (days) to each
      outcome were summarized by treatment. Meta-analysis (fixed-effects inverse
      variance model) was performed to compare outcomes for DA versus placebo. Safety
      was assessed by occurrence of adverse events. Data from 213 patients were
      analyzed: DA, n = 115; placebo, n = 98. More patients in the DA versus the
      placebo subgroup achieved Hb increase of >=1 g/dL (72% vs. 36%; HR: 2.92, 95% CI:
      1.95, 4.39) and >=2 g/dL (44% vs. 18%; HR: 2.98, 95% CI: 1.71, 5.21) during the
      first 12 treatment weeks. Median times to Hb increase of >=1 g/dL and >=2 g/dL
      were 36 days and 78 days for DA, respectively. RBC or whole blood transfusions
      were less common in patients in the DA versus the placebo subgroup (24% vs. 45%;
      HR: 0.44, 95% CI: 0.27, 0.73). No new safety issues were reported. Our results
      confirm that DA use in patients with Stage IV cancer and CIA is more effective
      than placebo at increasing Hb levels and at reducing transfusion needs when DA
      treatment is initiated at Hb <=10 g/dL.

PMID- 27882727
TI  - Advances in neurological research and practice.

PMID- 27882725
TI  - Analysis of risk factors to predict communicating hydrocephalus following gamma
      knife radiosurgery for intracranial schwannoma.
AB  - Communicating hydrocephalus (HCP) in vestibular schwannomas (VS) after gamma
      knife radiosurgery (GKRS) has been reported in the literature. However, little
      information about its incidence and risk factors after GKRS for intracranial
      schwannomas is yet available. The objective of this study was to identify the
      incidence and risk factors for developing communicating HCP after GKRS for
      intracranial schwannomas. We retrospectively reviewed a total of 702 patients
      with intracranial schwannomas who were treated with GKRS between January 2002 and
      December 2015. We investigated patients' age, gender, tumor origin, previous
      surgery history, tumor volume, marginal radiation dose, and presence of tumor
      control to identify associations with communicating HCP following GKRS. To make
      predictive models of communicating HCP, we performed Cox regression analyses and
      constructed a decision tree for risk factors. In total, 29 of the 702 patients
      (4.1%) developed communicating HCP following GKRS, which required ventriculo
      peritoneal (VP) shunt surgery. Multivariate analyses indicated that age (P =
      0.0011), tumor origin (P = 0.0438), and tumor volume (P < 0.0001) were
      significant predictors of communicating HCP in patients with intracranial
      schwannoma after GKRS. Using machine-learning methods, we fit an optimal
      predictive model. We found that developing communicating HCP following GKRS was
      most likely if the tumor was vestibular origin and had a volume >=13.65 cm3 .
      Communicating HCP is not a rare complication of GKRS for intracranial
      schwannomas. Under specific conditions, communicating HCP following GKRS is
      warranted for this patient group, and this patient group should be closely
      followed up.

PMID- 27882730
TI  - Corrigendum.

PMID- 27882729
TI  - Minocycline-induced human herpesvirus 6 encephalomyelitis with drastically
      disseminated contrast-enhanced lesions.

PMID- 27882726
TI  - The high expression instead of mutation of p53 is predictive of overall survival
      in patients with esophageal squamous-cell carcinoma: a meta-analysis.
AB  - Esophageal squamous-cell carcinoma (ESCC) is one of the deadliest cancers where
      biomarkers are needed for assist guiding management. We performed a meta-analysis
      to clarify the prognostic value of p53 high expression and TP53 mutations, which
      remain controversial for decades in patients with ESCC. We searched PubMed, Ovid
      MEDLINE, Embase, and Current Contents Connect to identify studies published
      between January 1990 and February 2016 of esophageal cancer populations that
      measured p53 expression and/or mutation status and reported hazard ratios (HRs),
      or adequate data for estimation of HRs for survival for p53-defined subgroups. We
      calculated pooled HR and 95% confidence interval (CI) using a random-effects
      model. A total of 56 eligible studies including 6537 patients were identified.
      The p53 high expression was associated with reduced survival (HR: 1.35, 95% CI:
      1.21-1.50, I2  = 42%). In subgroup analyses, a greater prognostic effect was
      observed in those studies that reported survival for pure ESCC cohorts and were
      assessed at low risk of bias (HR: 1.46, 95% CI: 1.29-1.65, I2  = 8%). Patients
      with ESCC and p53 high expression have reduced overall survival, and this effect
      is independent of tumor stage and greater than that of TP53 mutations.

PMID- 27882731
TI  - Reproducibility of corrected QT interval in pediatric genotyped long QT syndrome.
AB  - Reproducibility of corrected QT interval (QTc), especially QTc after exercise,
      has not been thoroughly investigated. We reviewed charts of pediatric patients
      who underwent treadmill-exercise stress testing without medication multiple times
      within 1 year. In patients with long-QT syndrome (LQTS; n = 22), the discrepancy
      in QTc between two treadmill exercise stress tests using Fridericia's formula was
      14 +/- 12 ms at rest, 13 +/- 12 ms 4 min after exercise, with a maximum of 14 +/-
      12 ms after exercise. There was no statistically significant difference in QTc
      between the two tests. Intraclass correlation coefficients (ICC) were 0.84, 0.85,
      and 0.85, respectively. In controls (n = 13), the discrepancy in QTc was 18 +/-
      12 ms at rest, 14 +/- 7 ms 4 min after exercise, with a maximum of 14 +/- 9 ms
      after exercise. There was no significant difference in QTc between the two tests.
      ICC were 0.78, 0.80, and 0.80, respectively. QTc calculated using Bazett's
      formula also showed high reproducibility. Reproducibility of QTc in children is
      high at rest and after exercise.

PMID- 27882732
TI  - Double pancreatic tumors in an adolescent: Imaging features.
AB  - Insulinoma is generally identified as a single tumor and seldom occurs in
      children or adolescents. A 14-year-old girl with difficulty in waking was found
      to have hyperinsulinemic hypoglycemia. On abdominal ultrasonography two
      hypoechoic masses (8 and 12 mm in diameter) were seen in the pancreatic body: the
      larger mass was hypervascular, whereas the smaller one was hypovascular. Contrast
      enhanced computed tomography showed enhancement of the larger mass, but did not
      delineate the smaller mass. On fat-suppressed T1-weighted magnetic resonance
      imaging, the larger mass was hypointense, but the smaller mass was hyperintense.
      Pathologically, the larger tumor was normal density, insulin positive, and rich
      in vascularity, whereas the smaller tumor was high density, insulin negative, and
      poor in vascularity. The present case suggests that difficulty waking should be
      considered as a potential etiology in insulinoma, and multiple suspected
      pancreatic insulinomas should be evaluated using a combination of imaging
      modalities to characterize each tumor.

PMID- 27882733
TI  - Anomalous origin of the right coronary artery: First familial cases in Asia.
AB  - Congenital coronary artery abnormalities may cause sudden death, particularly in
      athletes. Two siblings, aged 10 and 9 years, respectively, were diagnosed with
      anomalous origin of the right coronary artery on multi-detector computed
      tomography (MDCT). The right coronary artery arose from the left coronary cusp,
      and was wedged between the aorta and pulmonary artery. This was also noted on
      cardiac ultrasonography (UCG), but in general this might not be seen on
      electrocardiography at rest. Although the surgical indications are unclear in the
      case of unproven ischemia, early recognition of the condition may reduce risk of
      the cardiac events during exercise. The majority of proximal coronary artery
      anomalies can be screened for on UCG, and confirmed on MDCT, which yields more
      precise clinical details and is less invasive than angiography. This is the first
      report of familial cases of anomalous origin of the right coronary artery in
      Asia.

PMID- 27882734
TI  - Novel mutations in SH3TC2 in a young Japanese girl with Charcot-Marie-Tooth
      disease type 4C.
AB  - Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive
      demyelinating form of CMT characterized clinically by early onset and severe
      spinal deformities, and is caused by mutations in SH3TC2. We describe the case of
      a 10-year-old Japanese girl diagnosed with CMT4C. The patient developed
      progressive foot deformities such as marked pes cavus and ankle contracture, with
      mild muscle weakness in both legs, and generalized areflexia. On
      electrophysiological studies, motor nerve conduction velocity ranged from 22.3
      m/s in the tibial nerve to 48.2 m/s in the median nerve. Sensory nerve conduction
      velocity ranged from 30.3 m/s in the sural nerve to 52.8 m/s in the median nerve.
      Sequence analysis of candidate genes identified two novel heterozygous mutations,
      c.229C>T and c.2775G>A, in SH3TC2. The patient was diagnosed as having CMT4C with
      novel mutations, making this the first documented Japanese pediatric case.

PMID- 27882735
TI  - Education activities improve detection of growth abnormalities in young children.

PMID- 27882736
TI  - Crystalline nephropathy caused by tosufloxacin.
AB  - A 14-year-old girl was treated for 3 days with tosufloxacin (450 mg twice a day)
      for acute bronchitis and then developed acute kidney injury. Renal ultrasound
      showed enlarged kidneys without hydronephrosis. Urinalysis indicated drug crystal
      casts (2-3/HPF), consistent with drug-induced crystalline nephropathy. The
      patient recovered gradually with i.v. hydration and discontinuation of
      tosufloxacin, leading to the diagnosis of tosufloxacin crystalline nephropathy.
      Medical practitioners should be aware that crystalline nephropathy can occur in
      pediatric patients receiving tosufloxacin.

PMID- 27882737
TI  - Neonatal bowel strangulation: Rare presentation of congenital diaphragmatic
      hernia.
AB  - We report a case of congenital diaphragmatic hernia (CDH) with perinatal bowel
      strangulation requiring intestinal resection. Ten hours after birth, the newborn
      started to be lethargic and developed bilious emesis. X-ray documented distended
      loops of bowel with air fluid levels in the abdomen and a gasless, non
      homogeneous opacity of the left hemithorax, a right mediastinal shift and loss of
      the sharp left hemidiaphram line. On gastrographin enema the left colon was above
      the adjacent left diaphragm. Emergency surgery was performed at 16 h of age. The
      entire small bowel appeared reddish and compromised. After 24 h, second-look
      laparotomy was performed and only 25 cm of small bowel were viable. The
      postoperative period was uneventful. Neonatal bowel strangulation in CDH should
      be taken into account when estimating postnatal morbidity and mortality and, even
      if CDH treatment is not an emergency procedure, if gastrointestinal symptoms
      prevail over respiratory symptoms, surgery should be carried out without delay.

PMID- 27882738
TI  - Schistosoma haematobium infection is associated with increased urine foam.
AB  - We compared urine microscopy and dipstick results for urine foam from 59 children
      in a Schistosoma haematobium-endemic area in a blinded manner. The sensitivity
      and specificity, respectively, for diagnosing S. haematobium compared with
      microscopy was: 74% and 72% for the shake test; 61% and 97% for microscopic
      hematuria; and 43% and 83% for proteinuria. When >17 eggs/10 mL urine was
      detected on microscopy, the sensitivity and specificity, respectively, were: 100%
      and 72% for the shake test; 90% and 97% for microscopic hematuria; and 80% and
      83% for proteinuria. Urine foam height >34 mL was significantly more likely to
      have S. haematobium eggs detected on microscopy (P = 0.001) than urine foam <=34
      mL, indicating that S. haematobium-infected urine is associated with increased
      urine foam.

PMID- 27882739
TI  - Familial acute necrotizing encephalopathy without RANBP2 mutation: Poor outcome.
AB  - Most childhood cases of acute necrotizing encephalopathy (ANE) involve neither
      family history nor recurrence. ANE occasionally occurs, however, as a familial
      disorder or recurs in Caucasian patients. A mutation of RAN-binding protein 2
      (RANBP2) has been discovered in more than one half of familial or recurrent ANE
      patients. In contrast, there has been no report of this mutation in East Asia.
      Here, we report the first sibling cases of typical ANE in Japan, with poor
      outcome. DNA analysis of genes associated with ANE or other encephalopathies,
      including RANBP2 and carnitine palmitoyl transferase II (CPT2), indicated neither
      mutations nor disease-related polymorphisms. On literature review, recurrent or
      familial ANE without the RANBP2 mutation has a more severe outcome and greater
      predilection for male sex than that with the RANBP2 mutation. This suggests that
      there are unknown gene mutations linked to ANE.

PMID- 27882741
TI  - Bacteremia induced by Bifidobacterium breve in a newborn with cloacal exstrophy.
AB  - Bifidobacterium breve is an effective probiotic agent used in the field of
      neonatology. Although B. breve has been considered safe, a case of B. breve
      bacteremia has been reported. The pathogenic mechanism underlying the bacteremia
      is unknown. Herein, we report a second case of B. breve bacteremia that developed
      in a neonate with multiple abdominal organ anomalies. Following surgical repair
      immediately after birth, B. breve treatment was started. After 1 week, the infant
      developed B. breve bacteremia following the onset of adhesive ileus. The
      bacteremia was thought to have been associated with an intestinal obstruction. A
      pediatric culture bottle is theoretically unsuitable for incubating B. breve
      because B. breve is an obligate anaerobic bacterium. It was, however, cultured
      from pediatric culture bottles in the present case, suggesting that pediatric
      culture bottles may be useful for procuring B. breve and for determining
      antimicrobial susceptibility for screening purposes in neonatal patients.

PMID- 27882740
TI  - Sporadic pseudohypoparathyroidism type-1b with asymptomatic hypocalcemia.
AB  - Pseudohypoparathyroidism type 1b (PHP-1b) is usually diagnosed on various
      symptoms of hypocalcemia. Previous studies reported a few cases of autosomal
      dominant pattern PHP-1b identified on familial analysis with asymptomatic
      hypocalcemia. Herein we report the case of a 6-year-old male patient with
      sporadic PHP-1b incidentally detected on preoperative examination. He had neither
      characteristic findings of Albright hereditary osteodystrophy nor evidence of
      tetany. Sporadic PHP-1b was diagnosed on the basis of clinical observation and
      laboratory examination. In addition, genetic testing using methylation-specific
      multiplex ligation-dependent probe amplification indicated broad methylation
      abnormalities and confirmed the sporadic form of PHP-1b. Sporadic PHP-1b might
      often be overlooked when diagnosis is done simply on definitive clinical
      features. To avoid this, DNA sequencing and methylation analysis should be
      performed even in the absence of definitive clinical features.

PMID- 27882742
TI  - Esophageal adenocarcinoma and Barrett esophagus in a neurologically impaired
      teenager.
AB  - Esophageal adenocarcinoma (EAC) accompanied by Barrett esophagus (BE) is rare in
      patients younger than 20 years old. EAC in the upper esophagus is also rare. We
      report a rare case of EAC with BE that developed in the upper esophagus after
      chronic, untreated gastroesophageal reflux disease in a neurologically impaired
      teenager. A 19-year-old neurologically impaired man underwent endoscopy for
      evaluation of dysphagia and vomiting, and was diagnosed with EAC with BE. He
      underwent transthoracic esophagectomy, extensive lymph node dissection, and
      cervical esophagogastric anastomosis, but the prognosis was poor. Pathology
      indicated poorly differentiated adenocarcinoma with BE.

PMID- 27882743
TI  - Congenital nephrotic syndrome with a novel NPHS1 mutation.
AB  - Congenital nephrotic syndrome of the Finnish type (CNF) is a rare autosomal
      recessive disorder. The incidence of CNF is relatively high in Finland but
      considerably lower in other countries. We encountered a male newborn with CNF,
      associated with compound heterozygous mutations in nephrosis 1, congenital,
      Finnish type (NPHS1). The patient was admitted to hospital as a preterm infant.
      Physical and laboratory findings fulfilled the diagnostic criteria of nephrotic
      syndrome, and were compatible with a diagnosis of CNF, but there was no family
      history of the disease. On genetic analysis of NPHS1 a paternally derived
      heterozygous frame-shift mutation caused by an 8 bp deletion, resulting in a stop
      codon in exon 16 (c.2156-2163 delTGCACTGC causing p.L719DfsX4), and a novel,
      maternally derived nonsense mutation in exon 15 (c.1978G>T causing p.E660X) were
      identified. Early genetic diagnosis of CNF is important for proper clinical
      management and appropriate genetic counseling.

PMID- 27882744
TI  - Transpalpebral exenteration in cattle: a retrospective study of 115 cases.
AB  - OBJECTIVE: To describe the indications for exenteration and complications
      associated with the procedure. ANIMALS STUDIED: 115 cattle. PROCEDURES: Medical
      records of cattle presented for unilateral exenteration evaluated at the
      University of California, Davis Veterinary Medical Teaching Hospital from January
      1985 through December 2015 were reviewed. RESULTS: Median (range) age at
      presentation for all cattle was 6 (0.2-30) years. The most prevalent (80.9%)
      indication for exenteration was squamous cell carcinoma (SCC). Cattle >5 years
      had higher odds (OR = 11.2, 95% CI, 2.8-45.8) for undergoing exenteration due to
      SCC compared to cattle <=5 years. Herefords had higher odds (OR = 4.6, 95% CI,
      1.5-14.6) for undergoing exenteration for SCC compared to other breeds. Holsteins
      had higher odds (OR = 140.7, 95% CI, 7.5-2644) for undergoing exenteration for
      retrobulbar lymphoma compared to other breeds. Complications following
      exenteration were reported in 15 cases (13.0%). The postsurgical complications
      were orbital abscesses (6/15), recurrence of SCC (5/15), wound dehiscence (3/15),
      and excessive hemorrhage (1/15). Median (range) time to occurrence of
      postsurgical complications was 19 (5-205) days. There was no significant
      association (P > 0.05) between ocular diagnosis, age, anesthetic technique or the
      suture pattern used to close the skin postsurgically, and occurrence of
      postsurgical complications. CONCLUSIONS: Early clinical diagnosis of SCC by
      owners and veterinarians may prevent the need for exenteration. Owners should be
      made aware of the possible postsurgical complications following exenteration in
      cattle.

PMID- 27882745
TI  - [Comparison of perinatal mortality in Slovak Republic in the years 2007-2009 and
      in the years 2010-2012].
AB  - OBJECTIVE: Comparison of perinatal mortality in Slovak Republic in the years 2007
      2009 and in the years 2010-2012. DESIGN: Epidemiological perinatal nation-wide.
      SETTING: 1st Department of Gynaecology and Obstetrics School of Medicine,
      Comenius University and University Hospital, Bratislava, Slovak Republic.
      METHODS: The analysis of selected perinatal data prospectively collected in the
      years 2007-2009 and in the years 2010-2012. RESULTS: In the year 2007 there were
      63 maternity hospitals, 51,146 deliveries and that of live births 51,650 in
      Slovak Republic. In the years 2010-2012 decreased the number of maternity
      hospitals, total number of deliveries and that of live births from 57 to 55, from
      55,362 to 54,996 and from 55,901 to 55,643 respectively. Preterm deliveries rate
      increased from 7.4 to 7.7% and multiple pregnancies rate from 1.4% to 1.5% in the
      years 2010-2012 compared to years 2007-2009. Perinatal mortality rate decreased
      from 6.2 in the year 2007 to 5.1 per 1,000 still and live births in the year
      2012. During the years 2007-2012 stillbirth participate in perinatal mortality
      64%, low birth weight 65% and severe congenital anomalies 19%. Transport in utero
      to perinatal centres decreased in the years 2007-2012. It was from 64% to 56% for
      infants with very low birth weight and from 75% to 70% for infants with extremely
      low birth weight. CONCLUSION: In the year 2012 Slovak perinatology reach the best
      result in perinatal mortality rate 5.1 (0.51%). Centralisation of high-risk
      pregnancies, transport in utero very low birth weight infants, prenatal detection
      of severe congenital abnormalities and obstetric and neonatal intensive care
      units equipment need still to be improved in Slovak Republic.

PMID- 27882746
TI  - [Technique of pelvic and paraaortic lymphadenectomy].
AB  - OBJECTIVE: Overview of classification, anatomical conditions, methods and
      complications of pelvic and paraaortic lymph-node dissection. DESIGN: Review
      article. SETTING: Department of Obstetrics and Gynecology, General Faculty
      Hospital and 1st Medical Faculty, Charles University, Prague. MATERIALS AND
      METHODS: Lymphadenectomy is classified according to its extent into sentinel
      lymph-node biopsy, debulking, sampling and systematic procedure and according to
      approach into extraperitoneal or transperitoneal procedure. The most complex
      variant is systematic pelvic and paraaortic lymph-node dissection, which requires
      removal of fatty-lymphatic tissue from anatomically strictly defined areas.
      Procedure can be performed from laparotomy, laparoscopically or robotically.
      RESULTS: The main objective criterium of systematic procedure is the number of
      harvested nodes. The most common complications comprise bleeding and lymphocele
      formation. CONCLUSIONS: Pelvic and paraaortic lymphadenectomy represent basic
      component of surgical management in majority of gynecological cancers. The
      knowledge of extent, different techniques and ability to solve complications
      represents essential skill in gynecological oncology.

PMID- 27882747
TI  - [Present properties of ultrasound diagnostics in urogynecology].
AB  - OBJECTIVE: The review article describes properties of sonography diagnostics in
      urogynecology. DESIGN: Review article. SETTING: Department of Obstetrics and
      Gynaecology, Faculty of Medicine and Dentistry, Palacky University in Olomouc.
      MATERIAL AND METHODS: The review of sonography methods in urogynecology, their
      practical use for low urinary tract dysfunctions diagnostics, monitoring of
      surgical therapy effect and diagnostics of complications. CONCLUSION:
      Ultrasonography is inseparable part of urogynaecology examination, it is imaging
      method of the first choice to determine the exact diagnosis and indication for
      therapy, evaluation of postoperative conditions and solution of complications.

PMID- 27882749
TI  - [Severe immune thrombocytopenia diagnosed in pregnancy].
AB  - OBJECTIVE: The aim of this article is present a patient with severe immune
      thrombocytopenia in pregnancy. DESIGN: Case report. SETTING: Department of
      Obstetrics and Gynecology, University Hospital Olomouc, Faculty of Medicine,
      Palacky Univerzity Olomouc. CASE REPORT: Presents a patient with immune
      thrombocytopenia diagnosed in pregnancy. Severe thrombocytopenia was diagnosed
      incidentally. CONCLUSION: Severe immune thrombocytopenia is rare and substantial
      complication in pregnancy. In pregnancy is important cooperation between
      obstetritians and hematologists, in time of delivery neonatologists and
      anesthesiologists.

PMID- 27882748
TI  - [Application of the concetrations ratio of soluble receptor tyrosine kinase type
      1, and placental growth factor for short-term prediction and diagnosis of
      preeclampsia].
AB  - OBJECTIVE: Bring a comprehensive overview of the available information about
      applications of the concetration ratio of soluble receptor tyrosine kinase type 1
      (sFlt-1), and placental growth factor for short-term prediction and diagnosis of
      preeclampsia. DESIGN: Overview study. SETTINGS: Department of Midwifery, Faculty
      of Health Sciences, Olomouc; Department of Clinical Biochemistry, University
      Hospital Olomouc; Department of Obstetrics and Gynecology, University Hospital
      Olomouc; Department of Obstetrics and Gynecology, 2nd Faculty of Medicine,
      Charles University in Prague and Motol University Hospital. METHODS: Analysis of
      literary sources and databases Ovid, Medline (2001-2016). CONCLUSION:
      Preeclampsia is a multisystem disease with not fully understood etiology. This
      disease occurs in 2-5% of pregnant women. Preeclampsia is one of the main causes
      of global maternal and perinatal morbidity and mortality. It manifests itself as
      a newborn hypertension and proteinuria after 20 weeks of pregnancy in previously
      normotensive women. The only effective treatment is the delivery of the child.
      Diagnosis of preeclampsia comprises measuring blood pressure and proteinuria.
      These indicators have low diagnostic sensitivity and specificity. In
      preeclampsia, there is a decrease of serum levels of placental growth factor
      (PlGF). Soluble receptor tyrosine kinase type 1 (sFlt-1) is an antagonist of
      PlGF. Increased levels of sFlt-1 in proportion to the reduced level of PlGF are
      associated with an increased risk of preeclampsia. The sFlt-1/PlGF ratio can be a
      better predictive marker in the diagnosis of pre-eclampsia after 20 weeks of
      gestation.

PMID- 27882750
TI  - [Heart-attack in pregnancy].
AB  - OBJECTIVE: To describe hear-attack on crystal meth addicted pregnant woman.
      DESIGN: Case report. CONCLUSION: Acute heart-attack during pregnancy means
      unexpected obstetric complication. The consequences could be fatal for the mother
      and the fetus. Although good delivery management and treatment could reduce
      morbidity and mortality to a minimum.

PMID- 27882751
TI  - [Septic shock in pregnancy on the basis of an acute pyelonephritis].
AB  - OBJECTIVE: According to the World Health Organisation, sepsis is one of the four
      main causes of pregnancy-related mortality worldwide, together with hemorrhage,
      hypertensive disease and abortion. The main goal of this paper is an analysis of
      one case of septic shock in pregnancy. DESIGN: A case report. SETTING: Department
      of Obstetrics and Gynaecology of the First Faculty of Medicine and General
      Teaching Hospital, Prague. METHODS AND RESULTS: Authors would like to draw
      attention to the pitfalls of diagnosis and treatment of septic shock which
      developed in 25th week of pregnancy on the basis of pyelonephritis due to E.
      coli. CONCLUSIONS: Early diagnosis of sepsis and an interdisciplinary co
      operation are the main prerequisities for successful treatment.

PMID- 27882752
TI  - [Bronchopulmonary sequestration].
AB  - OBJECTIVE: To describe the case of prenatal diagnosis of bronchopulmonary
      sequestration and compelete spontaneous antenatal regresion of the lesion.
      DESIGN: Case report and review of the literature. SETTING: Complex Cancer Center
      Novy Jicin, Department of Obstetrics and Gynecology Palacky University Hospital
      Olomouc. CASE REPORT: We describe the case reports about the complete regression
      of a quite large bronchopulmonary sequestration during pregnancy. CONCLUSION:
      Bronchopulmonary sequestration is usually diagnosed in mid-trimester ultrasound
      fetal anomaly scan. In case of other fetal abnormalities are present the
      counceling by medical geneticist should be completed. In most cases complete
      spontaneous antenatal regresion of the lesion occur and the fetal surgery should
      be considered in adverse prognostic findings until 30 gestational weeks.

PMID- 27882753
TI  - [Hemangioblastoma cerebellum during pregnancy].
AB  - OBJECTIVE: Authors describe a case of woman in the age of 27 years, 36th+0 week
      of pregnancy, who was hospitalized for headache and vomittin. Magnestic resonance
      showed the cystic expansion in the left hemisphere of cerebellum with the
      overpressure in the IV. ventricle and wiht the beginning obstructive
      hydrocephalus. STUDY TYPE: Case report. SETTING: Hospital of Uherske Hradiste,
      Inc., Gynecology and Maternity Department. METHOD: Own observation.

PMID- 27882754
TI  - [Fetal alloimmune thrombocytopenia in pregnant woman with anti-HPA-1a
      antibodies].
AB  - OBJECT: Description of the pregnancy in patient with anti-HPA-1a antibodies.
      DESIGN: Case report. SETTING: Department of Obstetrics and Gynaecology, 2nd
      Faculty of Medicine, Charles University in Prague and Motol University Hospital.
      CASE REPORT: Report of cases of neonatal alloimune thrombocytopenia in a patient
      with proven anti-HPA 1a antibodies. The immunization developed during the first
      pregnancy, accompanied with fetal thrombocytopenia which recurred in every
      subsequent pregnancy with greater severity. None of the neonates was affected by
      intracranial hemorrhage.

PMID- 27882755
TI  - Prague 1337, the first successful caesarean section in which both mother and
      child survived may have occurred in the court of John of Luxembourg, King of
      Bohemia.
AB  - OBJECTIVE: An interdisciplinary historical-medical study, analysis of historical
      sources, and critical interpretation of the indirect evidence surrounding the
      childbirth of Beatrice of Bourbon, the second wife of the Bohemian King John of
      Luxembourg. STUDY TYPE: A material-based study founded on a comparative analysis
      of available private and public sources, particularly surviving letters, and
      narrative sources. The conclusions are reached based on a textual interpretation
      according to historical methods. SETTINGS: Department of Obstetrics and
      Gynecology of the First Faculty of Medicine of Charles University and General
      University Hospital in Prague. METHODS AND RESULTS: Until the second half of the
      19th century, medical knowledge of antiseptics and anesthesia was lacking, and
      techniques for cleaning wounds and staunching bleeding were primitive.Because no
      effective anesthetics were known before that time, people did not know how to
      perform painless abdominal surgery. There are a very few credible reports of
      caesarean sections performed on living women as early as the 17th century.
      However, before the 19th century, a caesarean section meant almost certain death
      for the mother, with related mortality as high as 90%. If the woman did not die
      of stress from the pain of the abdominal surgery, then she usually died of either
      bleeding or later of sepsis. However, there is some indirect evidence that the
      first caesarean section that was survived by both the mother and child was
      performed in Prague in 1337. The mother was Beatrice of Bourbon (1318-1383), the
      second wife of the King of Bohemia John of Luxembourg (1296-1346). Beatrice gave
      birth to the kings son Wenceslaus I (1337-1383), later the duke of Luxembourg,
      Brabant, and Limburg, and who became the half brother of the later King of
      Bohemia and Holy Roman Emperor, Charles IV (1316-1378). CONCLUSIONS: From a
      historical analysis based on the indirect evidence, it is not possible to
      unequivocally determine whether a caesarean section that was survived by both the
      mother and child was actually performed in the 14th century. From a medical
      standpoint in the context of all the known surrounding circumstances, however,
      this rare event could indeed have taken place.

PMID- 27882756
TI  - [The use of selective progesterone receptor modulators in the treatment of
      myomas].
AB  - OBJECTIVE: To summarize the knowledge of the effect of selective progesterone
      receptor modulators and their use in the treatment of myomas in women of
      childbearing age and in perimenopause. DESIGN: Review articleResults: Long-term
      treatment with ulipristal acetate maximizes its effectiveness, it helps to
      achieve faster bleeding control and increases the number of patients with fibroid
      volume reduction of more than 50%. Ulipristal acetate is the most effective drug
      in the medical treatment of myomas and its use will change the approach to
      surgical treatment.

PMID- 27882758
TI  - [Vulvar squamous precancerous lesions History and current state of the topic].
AB  - This review article discribes the genesis and development of vulvar squamous
      precancerous lesions terminology and discusses the consensus of the International
      Society for the Study of Vulvovaginal Disease, the American Society for
      Colposcopy and Cervical Pathology, College of American Pathologists and the World
      Health Organization on the current terminology. The article describes the
      different types of vulvar squamous precancerous lesions, according to their
      etiology, incidence and malignant potential.

PMID- 27882757
TI  - [Contribution of sentinel lymph-node biopsy to treatment of locally advanced
      stages of cervical cancers].
AB  - OBJECTIVE: Usage of sentinel lymph-node (SLN) concept in locally advanced
      cervical cancers might help to individualise management. According to SLN status
      could be patients refered to neoadjuvant chemotherapy (NAC) with subsequent
      surgery or to primary chemoradiation. The aim of our study was to evaluate
      sensitivity of SLN detection in locally advanced cervical cancers and to assess
      the impact of NAC on frequency of their metastatic involvement. DESIGN:
      Retrospective clinical study. SETTING: Department of Obstetrics and Gynecology,
      General Faculty Hospital and 1st Medical Faculty, Charles University, Prague.
      MATERIALS AND METHODS: Included were patients with cervical cancer stages FIGO
      IB1 (> 3 cm), IB2, IIA2 and selected cases of stages IIB with incipient
      parametrial involvement. Patients were distributed into two different protocols -
      patients in group NAC-SLN were refered to radical hysterectomy with SLN biopsy
      after 3 cycles of NAC, other patients (group SLN) underwent SLN biopsy and NAC
      was administered only in SLN-negative cases. RESULTS: Altogether 101 patients
      were included (group SLN = 62, group NAC-SLN = 39). Detection of SLN in whole
      cohort reached 90.1% per patient and 68.3% bilaterally. No differences were found
      between SLN group and NAC-SLN group in frequency of per patient SLN detection
      (90.3% vs 89.7%) and bilateral detection (69.4% vs 66.7%). Prevalence of
      macrometastases, micrometastases and ITC in the SLN group was 37.1% (23/62),
      11.3% (7/62) and 8.1% (5/62), respectively. In the NAC-SLN group macrometastases
      in SLN were detected in 17.9% (7/39) patients, in 1 patient was detected
      micrometastis in SLN and no patient had ITC. Difference in frequency of
      metastases in SLN was significant (p = 0,013). No patient had progressed during
      NAC, complete response was seen in 15.1% (11/73) patients and reduction of tumour
      volume > 30% in 84.9% (62/73) patients. CONCLUSIONS: Detection of SLN in locally
      advanced cervical cancers reached comparable results to early stages. NAC did not
      influence frequency of SLN detection, but it significantly decreased prevalence
      of metastatic SLN involvement.

PMID- 27882759
TI  - [Management of care of HIV-positive pregnant women in the period 1996-2014].
AB  - OBJECTIVE: The evaluation of multidisplinary care about HIV positive pregnant
      women in the Czech Republic. DESIGN: Review. SETTINGS: Gynekologicko-porodnicka
      klinika 1. LF UK a Nemocnice na Bulovce, Praha. METHODS: The vertical
      transmission of HIV infection from mother to fetus occurs most often during
      birth, still 1-2% of HIV-positive pregnant women will transfer the virus
      transplacenta. Due to careful screening for HIV during pregnancy, counselling,
      combination antiretroviral (cART) therapy, childbirth planning and its
      performance by C-section there appears a significant decrease of the virus
      transmission to the fetus, its occurrence is around 2%. If the HIV infection is
      detected in the context of screening for sexually transmitted infections (STIs),
      we begin with combined antiretroviral therapy (cART) depending on the level of
      viremia and CD4 as soon as possible. All HIV-positive pregnancies are tested for
      possible coinfection with hepatitis C. Since the first application of the
      antiretroviral treatment, the therapy is applies throughout the duration of the
      pregnancy. The labours of the HIV- positive women in the Czech Republic are
      scheduled. The primary choice is a caesarean section during the 38th week of
      pregnancy. CONCLUSION: From 1996-2014 the HIV positive status at 18 months of
      child age was confirmed in 4 cases in the Czech Republic. Three children were
      born to mothers whose HIV status was unknown at the time of the birth. Thanks to
      strict adherence to the interdisciplinary care, HIV positive woman have a chance
      to deliver a HIV-negative newborn and the risk of the transmission of the virus
      is significantly low.

PMID- 27882760
TI  - [Surgical treatment of endometriomas and ovarian reserve].
AB  - OBJECTIVE: To present an overview of affect an ovarian reserve in women after
      laparoscopic surgery for ovarian endometriosis. SUBJECT: Review. SETTING:
      Department of Obstetric and Gynecology, Hospital Kyjov; Department of Obstetric
      and Gynecology, University Hospital, Brno. METHODS: Summary of the results of
      recent studies. RESULTS: The decrease in ovarian reserve has been detected in 8
      of 9 evaluated studies, specifically in one retrospective study, six prospective
      studies and in one systematic review, the results of the meta-analysis don't
      prove the reduction of ovarian reserve after the surgery for endometrioma,
      reduced ovarian reserve evaluated by the antral follicle count has been proven in
      the affect ovary before the surgery. CONCLUSION: Endometriosis is among the most
      frequent benign gynecological diseases, affecting the women in reproductive age.
      Laparoscopic surgery techniques are currently the method of choice in the
      treatment of endometriotic ovarian cysts. Excision of endometriotic cyst is
      associated with significant reduction in ovarian reserve. The women with previous
      surgery of endometrioma have significantly fewer mature oocytes capable of
      fertilization, the ovarian response to stimulation is reduced and the number of
      live births is lower.

PMID- 27882761
TI  - [Paraneoplastic neurological syndromes in gynecological malignancies].
AB  - OBJECTIVE: The demonstration of life-threatening paraneoplastic syndrome with
      dominant neurological symptomatology in germinal ovarian malignancy. DESIGN:
      Literature review with case report. SETTING: Department of Gynecology and
      Obstetrics, Faculty of Medicine Masaryk University and University Hospital Brno.
      METHODS: The review outlines the issue of paraneoplastic syndromes. It describes
      the etiopathogenesis, the range of clinical symptoms, the diagnostic and
      therapeutic possibilities, along with a relevant case study which focuses on the
      paraneoplastic neurological symptoms in malignant germinal ovarian tumor.
      CONCLUSION: Although paraneoplastic symptomatology is rather rare, it constitutes
      an important part of the clinical picture of malignant tumors. In a number of
      cases, the paraneoplastic neurological syndrome (PNNS) symptoms precede the
      actual tumor diagnosis. The awareness of this connection can thus be important in
      early diagnostics, which in turn can significantly affect a patients prognosis.
      Another important benefit of familiarity with the symptoms of neurological
      paraneoplasia is the fact that some PNNS are associated with specific tumors.
      Interdisciplinary cooperation is necessary in the case of PNNS for early tumor
      diagnostics. Treatment of the primary tumor is the key in diagnosed malignancies.
      With effective oncological treatment, adequate regression of paraneoplastic
      symptoms can be observed.

PMID- 27882762
TI  - [The possibility of antepartal prevention of episiotomy and perineal tears during
      delivery].
AB  - OBJECTIVE: To determine the effect of antepartal methods on the prevention of
      birth injuries in primiparous women. DESIGN: Retrospective study. SETTING:
      Nemocnice Cesky Krumlov, a.s. METHODS: Between February 2014 and November 2015
      were 315 primiparous women questioned after a vaginal delivery on the use of
      methods of birth injury prevention (vaginal dilatators EPI-NO and Aniball,
      perineal massage, natural methods - raspberry-leaf tea or linseed).
      Consecutively, the rates of intact perineum, perineal tears and episiotomies
      among respective methods were compared with the control group using no preventive
      method. The effects of the methods were tested on the occurrence of spontaneous
      or vaginal operative delivery. RESULTS: There was a significantly higher number
      of women with intact perineum after the use of vaginal dilatators (43.1% vs.14.1%
      in control group (p < 0.001). We also found a significant reduction of
      episiotomies in this group (29.3% vs. 57.7%, p < 0.001). There was no significant
      effect of perineal massage, raspberry-leaf tea or linseed on perineum injury
      prevention. A lower occurrence of vaginal operative delivery was also confirmed
      in the group of women using vaginal dilatators (p = 0.02). CONCLUSION:
      Significant benefit of the use of the antepartal vaginal dilatators in the
      reduction of birth injuries was shown as well as of the occurrence of vaginal
      operative delivery.

PMID- 27882763
TI  - Effect of systemic enzymotherapy on Cesarean section scar healing.
AB  - OBJECTIVES: The aim of our study was to monitor changes in the healing of
      Caesarean section scars in patients using systemic enzymotherapy in comparison
      with patients not treated with systemic enzymotherapy (Wobenzym). METHODS: A
      prospective cohort study was conducted in 60 primiparous women delivered by CS.
      We compared the following outcomes: scar thickness after the Caesarean section,
      dehiscence risk coefficient (DRC), severity of the Caesarean section scar defect,
      uterine cavity dilation, post-operative pain, C-reactive protein level and
      febrility. RESULTS: The scar thickness 6 weeks after CS was significantly greater
      in the group of patients taking Wobenzym (7.1+/-0.9 mm; mean +/- SD) than in the
      patients without Wobenzym (5.3+/-0.7 mm) (p = 0.01). Severe Caesarean section
      scar defects were observed in 1/30 (3.3%) Wobenzym users and in 5/30 (16.7%)
      patients who did not use Wobenzym, with no statistically significant difference
      (p = 0.195). CONCLUSION: Despite the percentage of patients with a severe CS scar
      defect being apparently lower in the group treated with Wobenzym, the difference
      did not reach statistical significance due to the small size of the study
      population.

PMID- 27882764
TI  - [Acute pancreatitis in pregnancy, complicated by rupture of aneurysm of artery
      lienalis].
AB  - OBJECTIVE: We present a case of pregnant woman with acute pacreatitis in 38th
      week comlicated by acute rupture of aneurysm of artery lienalis. DESIGN: Case
      report. SETTING: Department of Gynaecology and Obstetrics, Faculty Hospital and
      Palacky University, Olomouc. CASE REPORT: 28-years-old primipara in 38th week of
      gestation was admitted to our department for acute pancreatitis caused by
      gallstones. Subsequent conservative treatment was complicated by rupture of
      aneurysm of lienal artery and haemorrhagic shock. Urgent caesarean section was
      performed with two subsequent revisions and peroperative 5l of blood loss.
      Operation was followed by intensive anesthesiology-resuscitate care of ARDS,
      gradual realimentation and conservative care of acute pancreatitis. Patient was
      discharged in good condition 20th day. CONCLUSION: Acute pancreatitis is rare in
      pregnancy. In severe and complicated cases maternal and perinatal morbidity and
      mortality may be elevated, despite early diagnosis and intensive treatment.

PMID- 27882765
TI  - [Spontaneus delivery after two previous caesarean sections - case report].
AB  - OBJECTIVE: To demonstrate the higher risk of the uterine dehiscence/rupture in
      spontaneously delivering women with scared uterus. DESIGN: Case report. SETTING:
      Department of Obstetrics and Gynecology, General Teaching Hospital in Prague and
      First Medical School, Charles University. CASE REPORT: We demonstrate the risk of
      uterine dehiscence on the example of 36 year-old woman with two previous
      caesarean sections who decided to give birth spontaneously. CONCLUSION: The scars
      on uterus are the risk factor for uterine dehiscence and rupture. In present, the
      rising number of caesarean sections leads to increasing number of women with
      scars on uterus. Despite the potential risk of scars on the uterus, small number
      of women with history of surgery on uterus plans to give birth spontaneously. We
      demonstrate the higher risk of the uterine dehiscence after spontaneous delivery
      in woman with history of two caesarean sections and successful conservative
      therapy.

PMID- 27882766
TI  - [Rupture of focal nodular hyperplasia in the 37th week of pregnanacy - case
      report].
AB  - OBJECTIVE: We describe a case of spontaneous hepatic rupture associated with
      undiagnosed focal nodular hyperplasia of a patient in the third trimester of
      pregnancy. Additionally, we provide a brief review of literature. DESIGN: Case
      report. SETTING: Department of Obstetrics and Gynaecology, 2nd Faculty of
      Medicine, Charles University in Prague and Motol University Hospital, Prague.
      RESULTS: We report the case of a 29 year old patient with otherwise physiological
      pregnancy, who was hospitalized with pain in left hypochondrium. The patient
      experienced painful respiration, increasing in intensity in supine position. The
      possibility of lung embolism was considered and ruled out. Based on a suspected
      haemoperitoneum, caesarean section was performed. During the inspection of
      peritoneal cavity a ruptured tumor on the liver was identified. Histological
      examination showed focal nodular hyperplasia. CONCLUSION: Focal nodular
      hyperplasia is a benign liver lesion. Complications involving rupture or bleeding
      are very rare. 17 cases of hepatic rupture associated with focal nodular
      hyperplasia were described in published reports with only one case related to
      pregnancy. Our case emphasizes the importance of a close cooperation between a
      gynaecologist, radiologist and surgeon.

PMID- 27882767
TI  - [Traumatic symphyseal rupture by vaginal delivery,report of a rare case].
AB  - OBJECTIVE: This case report draw attention symphysis pubic dysfunction and injury
      pelvic girdle by vaginal delivary (in our case compliated by dystokia shoulders),
      mainly its diagnostic, prediction and treatment. DESIGN: Case report. SETTING:
      Department of Obstetrics and Gynecology. Hospital Ceska Lipa. CASE REPORT: We
      report a case of a 31 years old woman, who gave birth for the second time with
      rupture of symphysis after delivery. Childbirth was complited by dystokia
      shoulders and patient was treated with external fixator. CONCLUSION: Pregnancy is
      a time of many physiological changes, these changes impact the musculosceletal
      system, which can develop a variety of problems, such es back pain, separation of
      the pelvic bones, transient osteoporosis and tendonitis. Effective management of
      treatment remains difficult to determine because of a variation in reported
      occurence rates and symptomatology. The most of cases are solved conservatively.
      This case report is extreme case of birth injury pelvic skeleton and it was
      necessary for surgery with an external fixator.This cases should be not to
      underestimate it and to treat it in interdisciplinary cooperation.

PMID- 27882768
TI  - [Adrenocortical oncocytoma presenting as Cushing's syndrome in pregnancy with
      spontaneous postpartum uterine rupture].
AB  - OBJECTIVE: The description of rare case of the Cushings syndrome in pregnancy
      resulting in the spontaneous rupture of uterus. DESIGNS: A case report. SETTING:
      Department of Gynecology and Obstetrics, 1st Medical Faculty of Charles
      University and Hospital Na Bulovce. CASE REPORT: The authors report the case of a
      33 year old woman, who was admitted to the clinic in 30th week of pregnancy for
      elevated blood pressure and hypokalemia. Arterial hypertension was corrected with
      the combination of Vasocardin and Dopegyt. In 36th week of pregnancy the patient
      was admitted to the hospital with premature rupture of membranes. In less than
      sixteen hours the patient spontaneously gave birth to a healthy girl.
      Subsequently the patient suffered from abdominal pain. CT scan showed
      haemoperitoneum and a right adrenal mass and the surgical revision was performed.
      During the surgery uterine rupture was identified and the patient uderwent
      abdominal hysterectomy. Based on the endocrinological examination the diagnosis
      of Cushings syndrome was made. Three months after the delivery she underwent
      laparoscopic right adrenalectomy. Histological examination revealed
      adrenocortical oncocytoma. CONCLUSION: Cushings syndrome is rare in pregnancy and
      misdiagnosis is common. Symptoms mimic pregnancy complications. The disease is
      often diagnosed with delay even after delivery. The sonography and magnetic
      resonance are dominant imaging methods. Laboratory diagnosis is difficult due to
      pregnancy related changes. In spite of rarity of Cushings syndrome in pregnancy
      we should think about it in terms of the differential diagnosis of hypertension,
      diabetes, dysbalance of mineralogram and typical cushingoid habitus.

PMID- 27882769
TI  - [Current issues of reproductive medicine in the Czech Republic].
AB  - INTRODUCTION: During the 25th symposium of assisted reproduction in Brno was
      lunch time organised as the lunch table discussion on the selected topics of
      assisted reproduction. More than 150 specialists reviewed themes related to
      gynecology and embryology.Discussed topics: Lunch table discussion covered the
      following topics: (1) Cross-border health care in assisted reproduction; (2)
      Indication for PGS (preimplantation genetic screening) in the context of actual
      information; (3) Does ovarian stimulation belong to the ambulance of registering
      gynecologists? (4) Therapy with clomifen - only for IVF specialists? (5) How and
      with whom should psychological support be directed during IVF? (6) Stimulation in
      women with low ovarian reserve; (7) Is basic semen analyses sufficient? (8) Time
      lapse systems as relevant markers of embryonic development; (9) How to be
      oriented with choices of media and consumables in the IVF lab, and (10) "Freeze
      All" - is this new trend in cryopreservation suitable for all? CONCLUSIONS: Panel
      conclusions were presented during the afternoon session, which had great
      attendance, featured lively commentary, and produced some definitive consensus.
      Certain issues remained inconclusive, and these matters will be the subject of
      further discussion in the future. Specific summation of all deductions is
      presented in this paper.

PMID- 27882770
TI  - Focal therapy as primary treatment for localized prostate cancer: definition,
      needs and future.
AB  - Focal therapy (FT) may offer a promising treatment option in the field of low to
      intermediate risk localized prostate cancer. The aim of this concept is to
      combine minimal morbidity with cancer control as well as maintain the possibility
      of retreatment. Recent advances in MRI and targeted biopsy has improved the
      diagnostic pathway of prostate cancer and increased the interest in FT. However,
      before implementation of FT in routine clinical practice, several challenges are
      still to overcome including patient selection, treatment planning, post-therapy
      monitoring and definition of oncologic outcome surrogates. In this article,
      relevant questions regarding the key steps of FT are critically discussed and the
      main available energy modalities are analyzed taking into account their
      advantages and unmet needs.

PMID- 27882771
TI  - Functional marine metagenomic screening for anti-quorum sensing and anti-biofilm
      activity.
AB  - Quorum sensing (QS), a cell-to-cell communication process, entails the production
      of signaling molecules that enable synchronized gene expression in microbial
      communities to regulate myriad microbial functions, including biofilm formation.
      QS disruption may constitute an innovative approach to the design of novel
      antifouling and anti-biofilm agents. To identify novel quorum sensing inhibitors
      (QSI), 2,500 environmental bacterial artificial chromosomes (BAC) from uncultured
      marine planktonic bacteria were screened for QSI activity using soft agar
      overlaid with wild type Chromobacterium violaceum as an indicator. Of the BAC
      library clones, 7% showed high QSI activity (>40%) against the indicator
      bacterium, suggesting that QSI is common in the marine environment. The most
      active compound, eluted from BAC clone 14-A5, disrupted QS signaling pathways and
      reduced biofilm formation in both Pseudomonas aeruginosa and Acinetobacter
      baumannii. The mass spectra of the active BAC clone (14-A5) that had been
      visualized by thin layer chromatography was dominated by a m/z peak of 362.1.

PMID- 27882773
TI  - The acquisition of initial consonant clusters in German-speaking 2-year-olds.
AB  - PURPOSE: The aim of this study was to explore cluster acquisition in typically
      developing German-speaking 2-year-olds. METHOD: Data from four cross-sectional
      studies (n = 145, aged 2;00-2;11) and one eight-month longitudinal study were
      analysed (n = 6, aged 2;01-2;04). Two different percentages of consonant clusters
      correct were calculated to allow a more detailed analysis. RESULT: Findings
      showed that the majority of children produced clusters, although they could not
      be considered to be fully acquired. Correct production significantly correlated
      with age. Only /gl/ and /kl/ were shown to be phonetically and phonemically
      acquired (75% criterion) in the older age group. Three-element clusters were
      acquired at the same time as 2-element clusters and /?/-clusters were acquired to
      the same or larger extent as non-/?/ clusters when fronting/backing of /?/ was
      accepted. Younger children produced more reductions than simplifications but this
      effect was less strong for the /?/-clusters. Developmental realisation patterns
      varied depending on cluster type. Inter- and intra-individual developmental
      patterns could be observed which changed depending on the time of testing.
      CONCLUSION: Findings on cluster acquisition in 2-year-old German-speaking
      children revealed language-specific differences but also similarities in
      comparison with results from other languages. All but two children produced
      clusters. However, individual variation between children was high.

PMID- 27882775
TI  - Association between availability of care providers and healthcare utilizations
      among adults with asthma.
AB  - BACKGROUND: Limited accessibility to providers may delay appropriate control of
      asthma exacerbations. The objective of our study is to estimate the contributors
      to the hospital/emergency department (ED) visits among adults with asthma
      focusing on the availability of healthcare providers. METHODS: We conducted a
      pooled cross-sectional analysis using the 2011-2013 Asthma Call-Back Survey
      linked with 2012-2016 Area Health Resource Files. We employed multivariable
      logistic regression with dichotomous outcomes of hospitalization and ED visits.
      Key covariates were the availability of county-level healthcare provider
      variables per 100,000 persons such as the number of lung disease specialists
      (including pulmonary care specialists, and allergy and immunology specialists),
      the number of hospitals, the number of safety-net facilities including rural
      health centers (RHCs) and federally qualified health centers (FQHCs), and the
      number of primary care physicians (PCPs). RESULTS: Among 25,621 adults,
      proportions of hospital visits and ED visits were 3.3% and 13.2%, respectively.
      An additional RHC reduced by 3% the odds of having an ED visit (odds ratio [OR] =
      0.97, p = .004). Patients with cost barriers to seeing a PCP were 60% (OR = 1.60,
      p = .028) more likely to have a hospital visit than those without. In addition,
      patients with cost barriers to seeing a specialist were 90% (OR = 1.90, p = .007)
      and 111% (OR = 2.11, p = .001) more likely to have a hospital visit and ED visit,
      respectively, than those without. CONCLUSIONS: Hospital and ED visits among
      adults with asthma are partially related to the availability of providers, and
      more related to financial barriers. Therefore, financial support for the
      vulnerable asthma population might be a target for policy makers interested in
      reducing hospitalizations and ED visits.

PMID- 27882774
TI  - Usefulness of copeptin as a potential biomarker in TBE.
AB  - OBJECTIVE: The aim of the study was to evaluate the usefulness of copeptin for
      differentiation of hyponatremia in the course of tick-borne encephalitis (TBE)
      and for being a prognostic marker of the severity of TBE. MATERIALS AND METHODS:
      One hundred and fourteen patients with TBE were included in the study. The
      control group consisted of 62 patients diagnosed with viral meningitis. RESULTS:
      Copeptin concentration did not differ in patients with hyponatremia and
      normonatremia. Urinary sodium excretion to plasma copeptin (copeptin/UNa
      Secretion) ratio was significantly lower in Syndrome of Inappropriate
      Antidiuretic Hormone (SIADH) Secretion patients than in patients with
      hyponatremia of other origin. Mean copeptin concentration in TBE patients was
      higher than in control group (VM) patients. There were no differences between
      patients with severe and mild course of TBE. CONCLUSIONS: Copeptin/UNa ratio may
      be used as a potential biomarker of SIADH in patients with TBE. Copeptin
      concentration is significantly higher in patients with TBE than in viral
      meningitis of other origin, especially in patients aged 18-34 and >49 years old.
      Copeptin does not differentiate TBE of mild and severe course.

PMID- 27882772
TI  - miRNAs differentially expressed by next-generation sequencing in cord blood buffy
      coat samples of boys and girls.
AB  - AIM: Differences in children's development and susceptibility to diseases and
      exposures have been observed by sex, yet human studies of sex differences in
      miRNAs are limited. MATERIALS & METHODS: The genome-wide miRNA expression was
      characterized by sequencing-based EdgeSeq assay in cord blood buffy coats from 89
      newborns, and 564 miRNAs were further analyzed. RESULTS: Differential expression
      of most miRNAs was higher in boys. Neurodevelopment, RNA metabolism and metabolic
      ontology terms were enriched among miRNA targets. The majority of upregulated
      miRNAs (86%) validated by nCounter maintained positive-fold change values;
      however, only 21% reached statistical significance by false discovery rate.
      CONCLUSION: Accounting for host factors like sex may improve the sensitivity of
      epigenetic analyses for epidemiological studies in early childhood.

PMID- 27882777
TI  - Real-time visual activity feedback for physical activity improvement in breast
      and colon cancer patients.
AB  - The study aims to evaluate the effects and feasibility of a biofeedback device
      for physical activity (PA) improvement in breast and colon cancer patients. Daily
      PA of 19 cancer patients was measured by accelerometry (ActiGraph, GT1 M).
      Additionally, patients wore a motion sensor with real-time visual activity
      feedback (ActiSmile). Counts per minutes (cpm) and moderate to vigorous physical
      activity (MVPA) were calculated and patients' activity data were compared to PA
      of 20 age-matched healthy controls. Baseline PA of patients was lower compared to
      controls. Following visual real-time feedback cancer patients increased cpm by
      21% (p = .002) and MVPA by 9% (p = .007) compared to baseline measurement. PA
      levels in cancer patients obtained with visual feedback became almost equal
      compared to age-matched healthy controls: cpm (301; IQR 170 vs. 299; IQR 111),
      MVPA (36; IQR 23 vs. 41; IQR 25 min/day). Activity biofeedback seems to be
      feasible to induce changes in patients' PA behaviour.

PMID- 27882776
TI  - Benefits of long-term therapy with nucleos(t)ide analogues in treatment-naive
      patients with chronic hepatitis B.
AB  - OBJECTIVE: To assess the benefits of long-term nucleos(t)ide analogue (NA)
      therapy in reducing the severity and progression of liver disease in treatment
      naive patients with chronic hepatitis B (CHB). SCOPE: As complications of CHB,
      such as hepatic decompensation and hepatocellular carcinoma (HCC), take a long
      time to develop in patients with less advanced disease, the long-term benefits of
      NA therapy in such patients are more difficult to prove than short- or medium
      term benefits. Thus, the recent literature was reviewed to evaluate the impact of
      NA therapy on the long-term outcomes of treatment-naive CHB patients. METHODS: A
      literature search of the MEDLINE/PubMed database was undertaken to identify
      studies published since 2010 of the long-term use of NAs with high potency and
      low drug resistance profiles in treatment-naive CHB patients. A total of 22
      studies were identified, many of which were retrospective analyses or case
      control studies, as well as three meta-analyses and one systematic review.
      RESULTS: Analysis of the retrieved studies showed that long-term NA therapy in
      treatment-naive CHB patients did prevent or delay the occurrence of
      complications, including hepatic decompensation, HCC, and liver-related death, in
      comparison with no treatment. However, it did not completely eliminate the risk
      of these complications, particularly in those with cirrhosis. Although long-term
      NA therapy improved the clinical status of patients with decompensated cirrhosis,
      the risk of cirrhotic complications including HCC, liver transplantation, and
      liver-related mortality remained significant in comparison with those with
      compensated cirrhosis. CONCLUSIONS: Long-term administration is generally advised
      in all CHB patients treated with NAs because of the high rates of virological and
      clinical relapse after stopping therapy. The findings of this analysis lend
      support to the choice of highly potent agents with a low drug resistance profile
      to maximize viral suppression in CHB patients and halt or delay progression to
      end-stage liver disease.

PMID- 27882778
TI  - Traditional medicine preparations and health risks: time to revisit their
      regulatory status.

PMID- 27882780
TI  - Solid lipid nanoparticles and nanostructured lipid carrier-based nanotherapeutics
      in treatment of psoriasis: a comparative study.
AB  - BACKGROUND: The present work focuses on the development of ultra-small solid
      lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) encapsulating
      cyclosporine and calcipotriol, further incorporated into gel, increasing their
      penetration through the skin. RESEARCH DESIGN AND METHODS: Developed SLN and NLC
      were characterized regarding particle size, zeta potential, %entrapment
      efficiency and dispersed into carbopol 934P-NF gel. Gel was further characterized
      for rheological behavior and spreadability. Ex vivo dermatokinetic by tape
      stripping method, in vitro efficacy on HaCaT cell lines and in vivo efficacy on
      imiquimod induced psoriatic model in mice were evaluated. RESULTS: Ultra-small
      (size<100 nm) particles were formed with high entrapment efficiency and spherical
      morphology. Ex vivo dermatokinetic studies revealed deeper and confined drug
      penetration of lipid formulation gel in epidermal layers as compared to free
      drug. In vitro study on HaCaT cell lines depicted higher uptake and high efficacy
      owing to decrease in cell viability for NLC. The anti-psoriatic efficacy in
      BALB/c mice (evaluated on basis of cytokine levels and skin morphology)
      highlighted potential of drug-loaded NLC significantly higher as compared to drug
      loaded SLN and marketed formulation Betagel. CONCLUSIONS: The study demonstrated
      that NLC gel had higher efficacy in psoriatic management and hold promise for
      further exploration.

PMID- 27882779
TI  - Ipilimumab: from preclinical development to future clinical perspectives in
      melanoma.
AB  - The arsenal for the treatment of metastatic melanoma is limited. A new approach
      to therapy using checkpoint blockade has improved overall survival in this
      patient population. Ipilimumab a CTLA-4 monoclonal antibody is a first in class
      drug that has pioneered this revolution. In this review, the authors provide an
      account of the different stages that led to the development of ipilimumab, its
      approval in the clinical setting for the treatment of advanced melanoma and
      ongoing investigations of combinatorial immune therapy.

PMID- 27882781
TI  - Age-related epigenetic drift and phenotypic plasticity loss: implications in
      prevention of age-related human diseases.
AB  - Aging is considered as one of the most important developmental processes in
      organisms and is closely associated with global deteriorations of epigenetic
      markers such as aberrant methylomic patterns. This altered epigenomic state,
      referred to 'epigenetic drift', reflects deficient maintenance of epigenetic
      marks and contributes to impaired cellular and molecular functions in aged cells.
      Epigenetic drift-induced abnormal changes during aging are scantily repaired by
      epigenetic modulators. This inflexibility in the aged epigenome may lead to an
      age-related decline in phenotypic plasticity at the cellular and molecular levels
      due to epigenetic drift. This perspective aims to provide novel concepts for
      understanding epigenetic effects on the aging process and to provide insights
      into epigenetic prevention and therapeutic strategies for age-related human
      disease.

PMID- 27882782
TI  - Lidocaine 5% medicated plaster for localized neuropathic pain in thoracic
      surgical patients.
AB  - CONTEXT: Neuropathic pain is a common and distressing symptom in thoracic
      surgical patients. When it consistently presents with measurable sensory changes
      in a circumscribed area, neuropathic pain can be diagnosed as localized
      neuropathic pain (LNP). OBJECTIVE: The purpose of this study was to report the
      efficacy of lidocaine 5% medicated plaster (Lido5%P) in the treatment of LNP in
      thoracic surgical patients. METHODS: We retrospectively reviewed the records of
      sixteen cancer and noncancer thoracic patients treated with Lido5%P for LNP.
      Patients had been assessed before and during treatment with standardized forms
      and questionnaires for pain intensity, sleep quality, drug dosages and adverse
      events. RESULTS: Treatment with Lido5%P yielded a significant and lasting
      improvement in pain symptomatology. In oncological patients as an add-on therapy,
      Lido5%P improved pain intensity and sleep quality, and delayed opioid dose
      escalation. In non-oncological patients as monotherapy or in association with
      antineuropathic drugs, Lido5%P attenuated LNP. No local or systemic adverse
      events were recorded. CONCLUSIONS: Lido5%P was effective in relieving thoracic
      LNP, and was well tolerated.

PMID- 27882784
TI  - Improving the resilience of the healthcare workforce.
AB  - Emeritus Professor Alan Glasper, from the University of Southampton, discusses
      government strategies to ensure a future healthcare workforce that is sustainable
      and does not rely on overseas recruitment.

PMID- 27882783
TI  - Communication about sex and HPV among Puerto Rican mothers and daughters.
AB  - OBJECTIVE: Although opportunities to vaccinate against human papillomavirus (HPV)
      are available, vaccination rates in Puerto Rico remain low. Communication between
      parents and adolescents about sexual topics may influence decisions about HPV
      vaccination uptake, particularly among young women; yet, few studies have
      addressed this issue. This qualitative study explored Puerto Rican mothers' and
      daughters' communication on sex-related topics, and HPV, including the HPV
      vaccine. DESIGN: Thirty participants, including 9 mothers and 21 daughters,
      participated in seven focus groups. Participants were divided into groups of
      mothers and daughters, and further stratified by vaccination status. Transcripts
      were analyzed using a modified grounded theory approach to identify emergent
      themes. RESULTS: Focus group data revealed four main themes: (1) limited parent
      daughter communication about sex-related topics; (2) daughters' discomfort
      discussing sex-related topics with their parents; (3) parental focus on
      abstinence; and, (4) limited parent-daughter communication about HPV and the HPV
      vaccine. CONCLUSION: Although daughters in this study struggled with feelings of
      embarrassment, invasion of privacy, encouragement of abstinence, and the fear of
      parents' reaction to them being sexually active prior to marriage, they also
      recognized the need to increase the parent-daughter communication about sex
      related topics including HPV and the HPV vaccine. Educational efforts should
      target both daughters and parents to increase communication skills and self
      efficacy and to enable them to discuss sexual health in open and nonjudgmental
      conversations.

PMID- 27882785
TI  - Ineligibility criteria and the authorisation of deprivations of liberty in
      hospitals.
AB  - Richard Griffith, Senior Lecturer in Health Law at Swansea University, highlights
      the problem of confusion over the circumstances in which a person can be subject
      to a deprivation of liberty safeguards authorisation.

PMID- 27882786
TI  - Managing clinical negligence litigation and costs in the NHS.
AB  - John Tingle, Reader in Health Law, Nottingham Trent University, discusses recent
      Government proposals to improve NHS maternity services and make changes to
      litigation and patient safety investigation procedures.

PMID- 27882787
TI  - Nurses' views on workplace wellbeing programmes.
AB  - Workplace stress is prevalent among nurses. Healthcare employers have implemented
      complementary and alternative therapies (CATs) for relaxation and stress
      management within workplace wellbeing programmes. In-depth interviews were
      conducted with 12 registered nurses to explore the perceptions and experiences of
      nurses towards accessing CATs in and outside the workplace. Interviews were audio
      recorded and transcribed verbatim. Data were analysed using conventional,
      qualitative thematic techniques. Themes identified were 'perceptions of
      complementary and alternative therapies for stress management' and 'engagement
      with workplace wellness schemes'. CATs have a role within workplace wellbeing
      programmes and nurses are not averse to accessing them, although there are
      barriers to access that need to be addressed.

PMID- 27882788
TI  - Why we need more research into interprofessional education.
AB  - Interprofessional education (IPE) has long been considered an important means of
      improving communication and interaction between health professionals and of
      addressing patient safety concerns. This study aimed to explore whether a high
      fidelity (HF) simulator could enhance a postgraduate IPE session on team-working
      and communication skills. A convenience sample of six doctors and six nurses, all
      recently qualified and working in an acute care setting, participated in teams of
      one nurse and one doctor in a typical clinical case scenario using a HF
      simulator. Pre-and post-test questionnaires and two focus groups were used to
      gather views on the IPE session. All of the participants agreed that all aspects
      of the IPE activity-the HF simulation, the scenarios and the debriefing-were
      'effective' in attracting and retaining interest and attention. Future larger
      scale research needs a more objective approach, such as a consideration of
      patient-related impact and outcomes.

PMID- 27882789
TI  - Advising patients on nutrition and healthy eating.
AB  - This article looks at the current UK guidelines for a healthy diet for the
      general population and considers the current debates and changes within that
      advice and how they may affect health outcomes. It is impossible to read a
      newspaper, magazine or social media article without being exposed to dietary
      advice, nutritional research or the latest diet craze. It is essential that
      nurses are able to advise their patients on research-based UK guidelines for a
      healthy diet, and be able to respond to patient questions on diet-related
      matters, ensuring the information they give is not based on current media opinion
      or celebrity views. This paper summarises the evidence found within current
      guidelines to help nurses ensure their practice is evidence based. This will help
      meet the requirements of the Nursing and Midwofery Council's (2015) Code,
      including delivering fundamentals of care and being able to practise in line with
      best available evidence.

PMID- 27882791
TI  - Ending transgender bias.

PMID- 27882790
TI  - Using health psychology to help patients: promoting healthy choices.
AB  - This article describes behaviour change techniques that nurses can use to help
      individual patients to make and stick to healthy choices. These include helping
      patients to set goals that are specific, measureable, achievable, relevant and
      timely (SMART), promoting self-monitoring and providing feedback and motivational
      interviewing. The process for delivering these techniques is described and the
      evidence for them discussed. Simply providing brief advice and follow up can lead
      to behaviour change, even in people who have not expressed a desire to change.
      The techniques are designed to be brief and feasible to use in routine practice.
      Using them can help nurses to apply the NHS policy of Making Every Contact Count
      so that their patients achieve long-term benefit.

PMID- 27882792
TI  - Smoke-free hospital site conversations: how nurses can initiate change.
AB  - Smoking tobacco continues to be the world's most preventable cause of death and
      disability with over six trillion cigarettes sold each year. Patients, visitors
      and health professionals who smoke on hospital sites present a challenge to the
      effectiveness of public health messages. Health professionals who ignore 'No
      smoking' hospital/clinic signage, and avoid smoking-cessation activity, help to
      sustain the perception that smoking is tolerated. Case studies, with a focus on
      lung cancer and chronic obstructive pulmonary disease (COPD), are used to
      illustrate how nurses can 'seed' the idea of hospitals becoming smoke-free,
      provide brief interventions and support patients, carers and colleagues to make
      that change.

PMID- 27882793
TI  - Encouraging positive interactions in dementia care.

PMID- 27882794
TI  - Assessment and management of the septic patient: part 2.
AB  - Sepsis has gained increasing publicity in recent years, and there is now a strong
      focus of clinical education and training following the Surviving Sepsis Campaign.
      The assessment and management of a septic patients is far from simple and
      requires a systematic approach in both identifying and managing the condition.
      This second part explores sepsis care bundles and the research that underpins
      each of the interventions. These discussions will enable nurses to understand why
      each component of the sepsis care bundle is important and thus enable them to
      rapidly prioritise care, as early effective interventions have been shown to
      optimise patient outcomes.

PMID- 27882795
TI  - Mental health and wellbeing: focus on men's health.
AB  - All nurses have a responsibility to ensure that they actively promote both mental
      and physical health and wellbeing. This article aims to bring together current
      thinking and evidence about nursing and men's mental health promotion. Key areas
      of concern outlined are the high rate of suicide in men, the expression of
      depression in men and the problems of masculinity when related to seeking help
      for mental health. The article highlights the importance of language and the
      normalising of distressing feelings when working with men and suggests that
      nurses need to recognise how men can experience depression differently, actively
      identify and address suicidal thinking, and provide gender-sensitive
      interventions. Additionally, nurses working with men need to demonstrate 'male
      positive' values and offer future-focused and action-oriented interventions (such
      as solution-focused, coaching or cognitive behavioural therapy approaches) that
      contribute to a sense of agency, promote hope and are more engaging for many men.

PMID- 27882796
TI  - Technology-enhanced learning in transnational higher education.
AB  - Some university schools of nursing in Australia and the UK have developed
      collaborative links with Malaysia to deliver part-time Transnational Higher
      Education (TNHE) post-registration top-up nursing degree courses. It enables
      nurses trained to diploma level to upgrade to a degree qualification. The views
      of 18 Malaysian nurses who had studied with one Australian and two UK TNHE
      universities were explored using a hermeneutic phenomenological approach.
      Participants recruited via convenience and snowball sampling methods were
      interviewed in English and Bahasa Malaysia (Malaysian language). Thematic
      analysis were used to analyse data. Findings indicated nurses' frustration with
      technology-enhanced teaching and learning and a lack of support throughout the
      programme. Although nurses developed confidence in using computer technology,
      they remained disappointed with the level of academic support. The data and some
      useful strategies outlined provide important insights for TNHE providers, the
      Malaysian Nursing Board and private hospital employers to consider for enhancing
      nurses learning and experiences.

PMID- 27882797
TI  - Reforming referral procedures.
AB  - Sam Foster, Chief Nurse at Heart of England NHS Foundation Trust, considers how
      fitness to practise referrals could be streamlined to increase efficiency and
      reduce delays in decisions being made.

PMID- 27882799
TI  - Skint, Shaken Yet Still Caring-highlighting hardship.
AB  - Cavell Nurses' Trust has recently published a report looking at nurses'
      experiences of hardship, both financial and emotional, and discusses the findings
      as well as the support available for nurses going through difficult times.

PMID- 27882798
TI  - Reflections on nurse education: past, present and future.
AB  - Janet Scammell, Associate Professor (Nursing), Bournemouth University, reflects
      on the changes in nursing that she has seen since beginning her nursing career 40
      years ago.

PMID- 27882800
TI  - Development of sorafenib-related side effects in patients diagnosed with advanced
      hepatocellular carcinoma treated with sorafenib: a systematic-review and meta
      analysis of the impact on survival.
AB  - Introduction: Clinical markers to predict the benefit from sorafenib in patients
      diagnosed with hepatocellular carcinoma (HCC) are lacking. A meta-analysis
      exploring the impact of development of sorafenib-related side effects on survival
      was conducted. Areas covered: Eligible studies included all clinical studies
      reporting on the survival/toxicity relationship in sorafenib-treated HCC
      patients. Data sources included Pub-Med, the Cochrane Controlled Trials Register,
      and Google scholar. After exclusion of ineligible studies, 16 studies were
      included in the analysis. Pooled hazard ratio (HR) for overall survival (OS) for
      patients developing diarrhoea vs. patients who did not was 0.42 (95% confidence
      interval (CI): 0.30-0.60; p < 0.00001); pooled HR for patients developing
      hypertension vs. those who did not was 0.46 (95% CI: 0.30-0.70; p = 0.0003);
      pooled HR for patients developing hand foot skin reaction vs. those who did not
      was 0.47 (95% CI: 0.35-0.62; p < 0.00001); pooled HR for OS for all types of skin
      toxicities was 0.51 (95% CI: 0.36-0.72; p = 0.0002); while pooled HR for OS for a
      combination of selected side effects (hypertension, HFS and diarrhoea) was 0.38
      (95% CI: 0.30-0.48; p < 0.00001). No information was available regarding the
      impact of thyroid dysfunction or proteinuria. Expert commentary: This analysis of
      data demonstrated that the occurrence of sorafenib-related side effects (such as
      diarrhoea, hypertension and skin toxicities) is associated with a better OS in
      sorafenib-treated HCC patients.

PMID- 27882801
TI  - Rapid assessment of the reactogenicity of a 2016-2017 seasonal influenza vaccine:
      results from a feasibility study.
AB  - BACKGROUND: The European Medicines Agency (EMA) calls for a strategy for enhanced
      safety surveillance of seasonal influenza vaccines. OBJECTIVE: We assessed the
      feasibility of collecting reactogenicity data within one month of the start of
      the vaccination campaign in Belgium. METHODS: One hundred subjects aged 18 to 65
      years who had received inactivated seasonal influenza vaccine in occupational
      setting were enrolled. For 7 days after vaccination, subjects received a daily
      SMS with a link to a web-based questionnaire where reactogenicity events and
      their severity were solicited. RESULTS: Data collection was completed by October
      13th, 2016, before the peak of the vaccination campaign in Belgium. 68% of
      participants reported a local reaction and 65% a general reaction; 51% reported
      both a local and a general reaction. CONCLUSION: Here we show that it has been
      possible to collect reactogenicity data in adults for enhanced safety
      surveillance in Belgium in a timely manner. The observed reactogenicity is higher
      compared to previous observations for this vaccine measured in clinical trials.

PMID- 27882803
TI  - Parental cardiac response in the context of pediatric acute pain: current
      knowledge and future directions.

PMID- 27882802
TI  - The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).
AB  - Background and purpose - To achieve a common understanding when dealing with long
      bone fractures in children, the AO Pediatric Comprehensive Classification of Long
      Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation,
      we present the most relevant fracture patterns in the upper extremities of a
      representative population of children classified according to the PCCF. Patients
      and methods - We included children and adolescents (0-17 years old) diagnosed
      with 1 or more long bone fractures between January 2009 and December 2011 at the
      university hospitals in Bern and Lausanne (Switzerland). Patient charts were
      retrospectively reviewed and fractures were classified from standard radiographs.
      Results - Of 2,292 upper extremity fractures in 2,203 children and adolescents,
      26% involved the humerus and 74% involved the forearm. In the humerus, 61%, and
      in the forearm, 80% of single distal fractures involved the metaphysis. In
      adolescents, single humerus fractures were more often epiphyseal and diaphyseal
      fractures, and among adolescents radius fractures were more often epiphyseal
      fractures than in other age groups. 47% of combined forearm fractures were distal
      metaphyseal fractures. Only 0.7% of fractures could not be classified within 1 of
      the child-specific fracture patterns. Of the single epiphyseal fractures, 49%
      were Salter-Harris type-II (SH II) fractures; of these, 94% occurred in
      schoolchildren and adolescents. Of the metaphyseal fractures, 58% showed an
      incomplete fracture pattern. 89% of incomplete fractures affected the distal
      radius. Of the diaphyseal fractures, 32% were greenstick fractures. 24 Monteggia
      fractures occurred in pre-school children and schoolchildren, and 2 occurred in
      adolescents. Interpretation - The pattern of pediatric fractures in the upper
      extremity can be comprehensively described according to the PCCF. Prospective
      clinical studies are needed to determine its clinical relevance for treatment
      decisions and prognostication of outcome.

PMID- 27882805
TI  - Free radical formation in chloramphenicol heated at different temperatures and
      the best thermal sterilization conditions - application of EPR spectroscopy and
      UV spectrophotometry.
AB  - Free radicals in thermally treated chloramphenicol were examined by electron
      paramagnetic resonance (EPR) spectroscopy. The parameters and shape of EPR
      spectra were analysed and free radical concentrations were obtained in the tested
      drug samples. Chloramphenicol was thermally sterilized at pharmacopeia
      conditions: 100  degrees C (120 min). Sterilization was also carried out at
      different conditions, 110  degrees C (60 min) and 120  degrees C (30 min), for
      comparison with pharmacopeia settings. Microbiological analysis was performed on
      the samples to confirm sterility. The aim of this work was to determine the
      concentration of free radicals in chloramphenicol following thermal sterilization
      at pharmacopeia conditions and compare this with other sets of conditions [110 
      degrees C (60 min) and 120  degrees C (30 min)]. The best conditions of thermal
      sterilization are determined as those that kill microorganisms and produce the
      lowest amounts of free radicals in this drug. It was concluded that the optimal
      temperatures and times for the thermal sterilization of chloramphenicol are 100 
      degrees C and 120 min and 110  degrees C and 60 min. A temperature of 120 
      degrees C coupled with a heating time of 30 min was rejected for thermal
      sterilization because of the high amount of free radicals produced by the drug
      samples.

PMID- 27882804
TI  - A comparison of high frequency chest wall oscillation and intrapulmonary
      percussive ventilation for airway clearance in pediatric patients with
      tracheostomy.
AB  - OBJECTIVES: The aim of this study was to compare two modes of airway clearance,
      the intrapulmonary percussive ventilation system (IPV) to high frequency chest
      wall oscillation system (HFCWO) in medically complex pediatric patients with
      tracheostomy requiring long term care. METHODS: This was a single center,
      retrospective study comparing the number of respiratory illnesses, lower
      respiratory tract infections (LRTI), utilization of bronchodilator and systemic
      steroids, and respiratory illnesses requiring acute care hospitalizations. A
      total of 8 tracheostomy dependent patients between the ages of 1-22 years were
      included for a 2-year study period. Each patient was used as their own control.
      During the period studied, the only variable in the medical regimen was the
      modality used for airway clearance. A Poisson regression model and generalized
      estimating equations were used to compare pre and post rates and to account for
      the correlation of count data from the same individual. Additionally, the paired
      differences (post-pre) for each event count were computed to provide the median
      and range of reductions in event rates while using intrapulmonary percussive
      ventilation system device. The non-parametric wilcoxon signed-rank test employed
      to determine whether the results from the Poisson model were consistently
      observed regardless of method of analysis. RESULTS: The total number of
      respiratory illnesses were reduced from 32 per year on HFCWO therapy to 15 per
      year on IPV system therapy (p < 0.001). The total number of LRTI requiring
      antibiotic use were decreased from 15 per year to 6 per year (p = 0.01), use of
      bronchodilator treatments were reduced from 53 to 21 (p < 0.001) and utilization
      of systemic steroids were reduced from 12 to 4 on IPV (p = 0.003). Numbers of
      hospitalizations to acute care facilities were reduced from 8 to 3
      hospitalizations during the period of IPV use for airway clearance (p = 0.003).
      CONCLUSION: This study suggests that airway clearance by IPV therapy could be
      more effective and beneficial in providing airway clearance in specific subsets
      of the medically complex pediatric population.

PMID- 27882806
TI  - Comorbidity as a predictor of overall survival in prostate cancer patients
      treated with external beam radiotherapy combined with HDR brachytherapy boosts.
AB  - BACKGROUND: The risk stratification currently applied prior to curative treatment
      for localized prostate cancer (PC) does not take into account comorbidity or age.
      Therefore, we investigated the impact of comorbidity on overall survival (OS) in
      PC patients treated with external beam radiotherapy (EBRT) and high-dose rate
      (HDR) brachytherapy boost. MATERIAL AND METHODS: At a single center, 611
      consecutive patients diagnosed with localized PC from 1998 to 2004 underwent
      definitive EBRT (50 Gy) and HDR brachytherapy boosts (2 * 10 Gy) combined with
      neoadjuvant total androgen blockade. Comorbidity was assessed with the Charlson
      comorbidity score. The impact of risk factors on OS and disease-free survival
      (DFS) was calculated using Cox proportional hazard ratios. Risk groups were
      defined as follows: low-risk PC: PSA <10, WHO grade 1 and T stage 1; high-risk
      PC: PSA >20 and/or WHO grade 3 and/or T stage 3a; intermediate-risk PC
      representing patients who did not fit either the low- or high-risk PC group.
      RESULTS: Mean age in the study cohort was 66.4 years, and 51% of the patients
      reported some degree of comorbidity. Divided into risk groups 8.2% were
      categorized as low-risk, 64% as intermediate-risk and 27.8% as high-risk PC.
      Overall 10-year survival was 72.2%, and 89% of the patients were relapse-free. In
      the univariate and multivariate analyses using Cox proportional hazard ratios,
      age, comorbidity and T stage were statistically significant predictors of OS:
      hazard ratios 1.56, 1.44 and 1.2 (p-values .002, .04 and .05), respectively. WHO
      grade, PSA at diagnosis, T stage and comorbidity were also significant predictors
      of DFS (p-values .0001, .0001, .009 and .003, respectively). CONCLUSION:
      Comorbidity assessed with the Charlson score predicts OS in patients with
      localized PC treated with curative intent using combined EBRT and HDR
      brachytherapy boost, and should be considered when making decisions before
      radical treatment.

PMID- 27882807
TI  - JARID1/KDM5 demethylases as cancer targets?

PMID- 27882808
TI  - No degeneration found in focal cartilage defects evaluated with dGEMRIC at 12
      year follow-up.
AB  - Background and purpose - The natural history of focal cartilage defects (FCDs) is
      still unresolved, as is the long-term cartilage quality after cartilage surgery.
      It has been suggested that delayed gadolinium-enhanced magnetic resonance imaging
      of cartilage (dGEMRIC) is a biomarker of early OA. We aimed to quantitatively
      evaluate the articular cartilage in knees with FCDs, 12 years after arthroscopic
      diagnosis. Patients and methods - We included 21 patients from a cohort of
      patients with knee pain who underwent arthroscopy in 1999. Patients with a full
      thickness cartilage defect, stable knees, and at least 50% of both their menisci
      intact at baseline were eligible. 10 patients had cartilage repair performed at
      baseline (microfracture or autologous chondrocyte implantation), whereas 11
      patients had either no additional surgery or simple debridement performed. Mean
      follow-up time was 12 (10-13) years. The morphology and biochemical features were
      evaluated with dGEMRIC and T2 mapping. Standing radiographs for Kellgren and
      Lawrence (K&L) classification of osteoarthritis (OA) were obtained. Knee function
      was assessed with VAS, Tegner, Lysholm, and KOOS. Results - The dGEMRIC showed
      varying results but, overall, no increased degeneration of the injured knees.
      Degenerative changes (K&L above 0) were, however, evident in 13 of the 21 knees.
      Interpretation - The natural history of untreated FCDs shows large dGEMRIC
      variations, as does the knee articular cartilage of surgically treated patients.
      In this study, radiographic OA changes did not correlate with cartilage quality,
      as assessed with dGEMRIC.

PMID- 27882809
TI  - Mechanisms of cell uptake, inflammatory potential and protein corona effects with
      gold nanoparticles.
AB  - AIM: To assess inflammation, cellular uptake and endocytic mechanisms of gold
      nanoparticles (AuNP) in human epidermal keratinocytes with and without a protein
      corona. MATERIALS & METHODS: Human epidermal keratinocytes were exposed to 40 and
      80 nm AuNP with lipoic acid, polyethylene glycol (PEG) and branched
      polyethyleneimine (BPEI) coatings with and without a protein corona up to 48 h.
      Inhibitors were selected to characterize endocytosis. RESULTS & CONCLUSION: BPEI
      AuNP showed the greatest uptake, while PEG-AuNP had the least. Protein coronas
      decreased uptake and affected their mechanism. AuNP uptake was energy-dependent,
      except for 40 nm lipoic-AuNP. Most AuNP were internalized by clathrin and lipid
      raft-mediated endocytosis, except for 40 nm PEG was by raft/noncaveolae mediated
      endocytosis. Coronas inhibited caveolae-mediated-endocytosis with lipoic acid and
      BPEI-AuNP and altered 40 nm PEG-AuNP from raft/noncaveolae to clathrin.
      Inflammatory responses decreased with a plasma corona. Results suggest protein
      coronas significantly affect cellular uptake and inflammatory responses of AuNP.

PMID- 27882812
TI  - Should we be treating lower risk myelofibrosis patients with a JAK2 inhibitor?
AB  - INTRODUCTION: Myelofibrosis (MF) is a Philadelphia chromosome-negative
      myeloproliferative neoplasm that is associated with debilitating constitutional
      symptoms, progressive splenomegaly, and cytopenias. Ruxolitinib, a JAK1/2
      inhibitor, is currently the only drug approved for the treatment of patients with
      intermediate or high risk MF. There is rationale and even limited clinical data
      supporting the use of ruxolitinib in lower risk patients, although this has not
      yet been validated in a randomized controlled trial. Areas covered: We examine
      rationale for using ruxolitinib in lower risk MF patients, including survival
      data from COMFORT-I and COMFORT-II, specific patient populations that may derive
      clinical benefit, and the future impact of molecular analysis on risk
      stratification and treatment. Additionally, we consider the potential risks
      associated with earlier intervention with ruxolitinib therapy. Expert commentary:
      Although there exists rationale for the use of JAK2 inhibitor therapy in lower
      risk MF patients, we eagerly await the results of an ongoing randomized
      controlled trial addressing this question before recommending wider use in the
      community setting.

PMID- 27882810
TI  - What has changed in the prevalence of hypertension in dialyzed children during
      the last decade?
AB  - BACKGROUND: Hypertension very often accompanies progression of chronic kidney
      disease (CKD) in children. A cross-sectional analysis of hypertension prevalence
      in dialyzed children in Poland was designed with a comparison with the data
      previously recorded 10 years earlier. METHODS: Two cohorts of children were
      analyzed: 59 subjects dialyzed in 2013, and 134 children from the previous study
      performed in 2003 that were reevaluated according to the current methodology. The
      incidence of hypertension (defined by SDS of sBP or dBP >1.64), clinical data,
      medical history, dialysis modalities and selected biochemical parameters of
      dialysis adequacy were analyzed. RESULTS: The prevalence of hypertension
      increased from 64% in 2003 to 78% in 2013. The efficacy of antihypertensive
      treatment remained unsatisfactory (61% proper BP control). Preservation of
      residual urine output and strict fluid balance may prevent development of
      hypertension in children on dialysis. CONCLUSIONS: Despite the higher awareness
      of hypertension and its complications in dialyzed children, the incidence of this
      entity has increased during the last decade, with the percentage of undertreated
      patients comparable to that observed 10 years ago. Thus, more attention should be
      paid to therapy efficacy in this population to prevent further damage to the
      cardiovascular system and to decrease morbidity.

PMID- 27882811
TI  - The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).
AB  - Background and purpose - To achieve a common understanding when dealing with long
      bone fractures in children, the AO Pediatric Comprehensive Classification of Long
      Bone Fractures (AO PCCF) was introduced in 2007. As part of its final validation,
      we present the most relevant fracture patterns in the lower extremities of a
      representative population of children classified according to the PCCF. Patients
      and methods - We included patients up to the age of 17 who were diagnosed with 1
      or more long bone fractures between January 2009 and December 2011 at either of 2
      tertiary care university hospitals in Switzerland. Patient charts were
      retrospectively reviewed. Results - More lower extremity fractures occurred in
      boys (62%, n = 341). Of 548 fractured long bones in the lower extremity, 25%
      involved the femur and 75% the lower leg. The older the patients, the more
      combined fractures of the tibia and fibula were sustained (adolescents: 50%, 61
      of 123). Salter-Harris (SH) fracture patterns represented 66% of single
      epiphyseal fractures (83 of 126). Overall, 74 of the 83 SH patterns occurred in
      the distal epiphysis. Of all the metaphyseal fractures, 74 of 79 were classified
      as incomplete or complete. Complete oblique spiral fractures accounted for 57% of
      diaphyseal fractures (120 of 211). Of all fractures, 7% (40 of 548) were
      classified in the category "other", including 29 fractures that were identified
      as toddler's fractures. 5 combined lower leg fractures were reported in the
      proximal metaphysis, 40 in the diaphysis, 26 in the distal metaphysis, and 8 in
      the distal epiphysis. Interpretation - The PCCF allows classification of lower
      extremity fracture patterns in the clinical setting. Re-introduction of a
      specific code for toddler's fractures in the PCCF should be considered.

PMID- 27882813
TI  - Dietary zinc modifies diabetic-induced renal pathology in rats.
AB  - This study was conducted to investigate how far dietary zinc (Zn) modifies the
      histomorphological alterations induced by diabetes in rat kidneys. The animals
      were divided into negative control group (10 rats). Diabetes was induced in
      thirty animals by streptozotocin. After confirming diabetes, the animals were
      divided into three groups (n = 10). Group II served as the positive control group
      (fed on standard diet), group III was fed on Zn deficient diet, and group IV was
      fed on Zn supplemented diet. Caspase-3 immune staining was used to estimate the
      caspase activity. Stereological procedures were used to measure the quantity of
      the immune stain and the surface area of the Bowman's space. The renal cortices
      of group II rats revealed apparent widening of Bowman's spaces with few apoptotic
      figures. The filtration barrier showed thickening of the basement membrane. The
      proximal convoluted tubules showed patchy loss of the apical microvilli with
      swollen mitochondria. The distal convoluted tubules revealed area of irregular
      basal enfolding. The picture was aggravated by Zn deficiency in group III besides
      areas of cortical interstitial fibrosis. The histopathological alterations were
      minimal in the cortices of group IV. A significant increase of the Bowman's space
      surface area in group II and IV while decrease in group III compared with group
      I. The expression of Caspase-3 density was significantly increased in group II
      and III compared with group I while in group IV was non significant. In
      conclusion, dietary Zn modulated renal cortical changes caused by diabetes in
      rats.

PMID- 27882814
TI  - The AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF).
AB  - Background and purpose - The AO Pediatric Comprehensive Classification of Long
      Bone Fractures (PCCF) describes the localization and morphology of fractures, and
      considers severity in 2 categories: (1) simple, and (2) multifragmentary. We
      evaluated simple and multifragmentary fractures in a large consecutive cohort of
      children diagnosed with long bone fractures in Switzerland. Patients and methods 
      Children and adolescents treated for fractures between 2009 and 2011 at 2
      tertiary pediatric surgery hospitals were retrospectively included. Fractures
      were classified according to the AO PCCF. Severity classes were described
      according to fracture location, patient age and sex, BMI, and cause of trauma.
      Results - Of all trauma events, 3% (84 of 2,730) were diagnosed with a
      multifragmentary fracture. This proportion was age-related: 2% of
      multifragmentary fractures occurred in school-children and 7% occurred in
      adolescents. In patients diagnosed with a single fracture only, the highest
      percentage of multifragmentation occurred in the femur (12%, 15 of 123). In
      fractured paired radius/ulna bones, multifragmentation occurred in 2% (11 of
      687); in fractured paired tibia/fibula bones, it occurred in 21% (24 of 115),
      particularly in schoolchildren (5 of 18) and adolescents (16 of 40). In a
      multivariable regression model, age, cause of injury, and bone were found to be
      relevant prognostic factors of multifragmentation (odds ratio (OR) > 2).
      Interpretation - Overall, multifragmentation in long bone fractures in children
      was rare and was mostly observed in adolescents. The femur was mostly affected in
      single fractures and the lower leg was mostly affected in paired-bone fractures.
      The clinical relevance of multifragmentation regarding growth and long-term
      functional recovery remains to be determined.

PMID- 27882816
TI  - Long-term studies of treatments for type 2 diabetes.
AB  - There is a relative lack of long-term data for individual glucose-lowering
      therapies for the treatment of type 2 diabetes mellitus. A systematic search of
      published literature reporting data of approximately >=3 years of follow-up from
      randomized controlled trials and their extensions was conducted. Trials to
      evaluate the efficacy and/or safety of glucose-lowering drugs currently approved
      for the treatment of adults with type 2 diabetes were included. Search results
      included long-term published data for traditional oral glucose-lowering drugs,
      insulin, alpha-glucosidase inhibitors, and incretin-based therapies. In general,
      results indicated that the short-term risk/benefit profile of these therapies is
      in line with longer-term evaluations. Individual results from these trials are
      reviewed in this report. These findings support the use of approved drug classes
      for longer-term treatment of type 2 diabetes.

PMID- 27882815
TI  - Approaches to developing fast release pellets via wet extrusion-spheronization.
AB  - Microcrystalline cellulose (MCC) is widely regarded as the excellent choice to
      manufacture pellets via wet extrusion-spheronisation (ES) process due to its
      excellent water uptake capability, water holding capacity, desirable rheological
      properties, cohesiveness and plasticity etc. Nevertheless, in spite of all these
      advantages, limitations associated with the application of MCC also have been
      reported. The most prevailing limitation is prolonged or incomplete drug release
      profile due to the lack of disintegration as pellet contracts significantly
      during the drying process, especially when in combination with poorly soluble
      drug at a high level. This characteristic limits the application of MCC in
      immediate release formulations. Over the years, many approaches have been tried
      to overcome this disadvantage, such as modifying MCC, incorporation of
      superdisintegrant, increasing the porosity of pellet, partial or complete
      substitution for MCC, enhancing the solubility of poorly soluble drug (e.g. solid
      dispersion, self-emulsifying drug-delivery system), etc. In this review, we will
      provide an updated and integrated discussion of current approaches to prepare
      fast release pellets via wet ES.

PMID- 27882818
TI  - Comparison of lumbosacral transforaminal epidural steroid injection techniques in
      terms of radiation safety.
AB  - AIM: To investigate the difference in radiation exposure to the patients between
      oblique and posteroanterior view, initial approach techniques in fluoroscopy
      guided lumbosacral transforaminal epidural steroid injections. PATIENTS &
      METHODS: Total amount of Kerma area product, elapsed time of the procedure and
      fluoroscopy time were obtained from medical records retrospectively. RESULTS: 28
      patients were included in each group. Fluoroscopy time was significantly lower in
      group 1, but there was no statistically significant difference in terms of
      procedure time and Kerma area product. CONCLUSION: Radiation risk does not change
      between these approaches.

PMID- 27882817
TI  - H2S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF
      beta1 expression.
AB  - Nephropathy develops in many patients with type 1 diabetes mellitus (T1DM).
      However, the specific mechanisms and therapies remain unclear. For this purpose
      we investigated the effects of hydrogen sulfide (H2S) on renal fibrosis in
      streptozotocin (STZ) induced diabetic rats and its underlying mechanisms.
      Experimental rats were randomly divided into four groups: Control group (normal
      rats), DM group (diabetes rats), DM + NaHS group [diabetes rats treated with
      sodium hydrosulfide (NaHS)], and NaHS group (normal rats treated with NaHS). The
      diabetic models were established by intraperitoneal injection of STZ. The NaHS
      treated rats were injected with NaHS as an exogenous donor of H2S. At the same
      time, control group and DM group were administrated with equal doses of normal
      saline (NS). After eight weeks, the rats' urine samples were collected to measure
      the renal hydroxyproline content by basic hydrolysis method with a hydroxyproline
      detection kit. Collagen I and III content was detected by immunohistochemical
      method, and the pathology morphology of kidney was analyzed by Masson staining.
      Protein expressions of transforming growth factor beta 1 (TGF-beta1), ERK1/2,
      TIMP1, TIMP2, MMP-2, MMP-7, MMP-8, MMP-11, and MMP-14 were assessed by western
      blotting. The results showed that significant fibrosis occurred in the kidney of
      diabetes rats. NaHS treatment downregulated TGF-beta1, ERK1/2, TIMP1, TIMP2, MMP
      2, MMP-7, MMP-8, MMP-11, and MMP-14 expressions in the kidney of these diabetes
      rats (p<.01). This result suggests that NaHS treatment could attenuate renal
      fibrosis by TGF-beta1 signaling, and its mechanisms may be correlated with ERK1/2
      expression and modulation of MMPs/TIMPs expression. Therefore, H2S may provide a
      promising option for defensing against diabetic renal fibrosis through TGF-beta1
      signaling, equilibrating the balance between profibrotic and antifibrotic
      mediators.

PMID- 27882819
TI  - Cross-cultural adaptation of the assistive technology device - Predisposition
      assessment (ATD PA) for use in Brazil (ATD PA Br).
AB  - PURPOSE: The purpose of this study is to conduct a cross-cultural adaptation of
      the Assistive Technology Device Predisposition Assessment (ATD PA) for use in
      Brazil. METHOD: The selection of the Assistive Technology Device Predisposition
      Assessment (ATD PA) was determined by previous literature reviews of articles
      published in 2014 and 2016 in six databases with the terms "assistive device" or
      "assistive technology" or "self-help device" combined with "evidence-based
      practice" or "framework" or "measurement scale" or "model and outcome
      assessment". This review indicated that the conceptual model of Assistive
      Technology (AT) most discussed in the literature was the Matching Person and
      Technology (MPT) model, and this finding determined the selection of ATD PA as an
      assessment within the MPT portfolio of measures. The procedures for cross
      cultural adaptation were as follows: Equivalence of Concept, Semantic and
      Operational. Five experts were asked to translate 725 items and these
      translations were evaluated and a high level of agreement was demonstrated.
      RESULTS: The Portuguese version, Avaliacao de Tecnologia Assistiva -
      Predisposicao ao Uso - ATD PA Br, was derived from the original version in
      English (ATD PA). CONCLUSION: The ATD PA Br will support professionals and people
      with disabilities in Brazil to better select AT devices according to the clients'
      needs. Implications for rehabilitation Provides a systematic way of selecting
      assistive technology devices for the use of individuals with disabilities
      according to the Brazilian reality. A systematic way of selecting the assistive
      technology that can help decrease the abandonment of the assistive technology
      use. The use of the Matching Person and Technology theorical model and of the
      assessment ATD PA Br is essential to guide the researches and clinical practice
      in Brazil.

PMID- 27882821
TI  - A description of assistive technology sources, services and outcomes of use in a
      number of African settings.
AB  - : Purpose statement: The article explores assistive technology sources, services
      and outcomes in South Africa, Namibia, Malawi and Sudan. METHODS: A survey was
      done in purposively selected sites of the study countries. Cluster sampling
      followed by random sampling served to identify 400-500 households (HHs) with
      members with disabilities per country. A HH questionnaire and individual
      questionnaire was completed. Country level analysis was limited to descriptive
      statistics. RESULTS: Walking mobility aids was most commonly bought/provided
      (46.3%), followed by visual aids (42.6%). The most common sources for assistive
      technology were government health services (37.8%), "other" (29.8%), and private
      health services (22.9%). Out of the participants, 59.3% received full information
      in how to use the device. Maintenance was mostly done by users and their families
      (37.3%). Devices helped a lot in 73.3% of cases and improved quality of life for
      67.9% of participants, while 39.1% experienced functional difficulties despite
      the devices. CONCLUSION: Although there is variation between the study settings,
      the main impression is that of fragmented or absent systems of provision of
      assistive technology. Implications for rehabilitation Provision of assistive
      technology and services varied between countries, but the overall impression was
      of poor provision and fragmented services. The limited provision of assistive
      technology for personal care and handling products is of concern as many of these
      devices requires little training and ongoing support while they can make big
      functional differences. Rural respondents experienced more difficulties when
      using the device and received less information on use and maintenance of the
      device than their urban counterparts. A lack of government responsibility for
      assistive device services correlated with a lack of information and/or training
      of participants and maintenance of devices.

PMID- 27882820
TI  - Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to
      docetaxel in patients with previously treated, locally advanced or metastatic non
      small cell lung cancer.
AB  - BACKGROUND: The primary objective of this study was to compare the progression
      free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway
      modulator AXL1717 (AXL) and patients treated with docetaxel (DCT). MATERIAL AND
      METHODS: The study was conducted at 19 study centers in five countries. A total
      of 99 patients with previously treated, locally advanced or metastatic non-small
      cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma
      (AC) subtypes in need of additional treatment were randomized and treated with
      either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as
      75 mg/m2 in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for
      each NSCLC subtype. Patients were treated in the primary study treatment period
      for a maximum of four treatment cycles. RESULTS: The 12-week PFS rate, median PFS
      and overall survival (OS), as well Kaplan-Meier hazard ratio for PFS and OS, did
      not show any statistically significant differences between the treatment groups.
      For the primary endpoint, the AXL group had a lower percentage of patients
      (25.9%) who were progression-free at Week 12 as compared to the DCT group
      (39.0%), although the difference was not statistically significant. The most
      notable difference in the incidence of treatment emergent adverse effects (TEAEs)
      was the lower incidence of treatment-related grade 3/4 neutropenia in patients
      treated with AXL. CONCLUSION: These results suggest neither of the treatments to
      be superior of the other when treating locally advanced or metastatic NSCLC.
      Considering the lower incidence of grade 3/4 neutropenia in the AXL group this
      treatment warrants further research.

PMID- 27882822
TI  - A protective role for herpes simplex virus type-1-specific humoral immunity in
      Alzheimer's Disease.

PMID- 27882823
TI  - The transparency of published health technology assessment-based recommendations
      on pharmaceutical reimbursement in Poland.
AB  - BACKGROUND: The appropriate access to public information is very important for
      healthcare system stakeholders. The goal of this study was to examine how the
      execution of the formally existing right to public information on the HTA-based
      recommendations on reimbursement of new health technologies from public funds has
      been changing in Poland. METHODS: All recommendations published within two
      predefined equal periods of time between 2013 and 2015 were analyzed. The
      gathered data was subjected to statistical analysis. RESULTS: The frequency and
      intensity of censoring the published HTA-based recommendations on the
      pharmaceutical reimbursement has diminished. The text readability and clarity of
      message has improved, although the degree of decisiveness of the recommendations
      has dropped. CONCLUSION: The positive changes in the public communication policy
      should be continued. The transparency of the HTA-based recommendations should be
      increased further in some areas in the future.

PMID- 27882824
TI  - Simultaneous recovery of phosphorus and potassium as magnesium potassium
      phosphate from synthetic sewage sludge effluent.
AB  - Bench-scale experiments were performed to investigate simultaneous recovery of
      phosphorus and potassium from synthetic sewage sludge effluent as crystals of
      magnesium potassium phosphate (MPP or struvite-(K), MgKPO4.6H2O). The optimal pH
      of MPP formation was 11.5. A phosphorus level of at least 3 mM and K:P molar
      ratio over 3 were necessary to form MPP, which showed higher content rate of
      phosphorus and potassium in precipitate. MPP crystallization was confirmed by
      analysing the precipitates using a scanning electron microscope-energy dispersive
      X-ray spectroscopy (SEM-EDX) apparatus and an X-ray Diffractometer (XRD).
      Inhibition of MPP crystallization by iron and aluminium was confirmed by
      precipitation experiments and SEM-EDX analysis. Potassium ratio against magnesium
      in precipitate decreased for iron concentrations greater than over 0.2 mM and
      aluminium concentrations over 0.05 mM.

PMID- 27882825
TI  - Validity and reliability of a low-cost digital dynamometer for measuring
      isometric strength of lower limb.
AB  - Lower limb isometric strength is a key parameter to monitor the training process
      or recognise muscle weakness and injury risk. However, valid and reliable methods
      to evaluate it often require high-cost tools. The aim of this study was to
      analyse the concurrent validity and reliability of a low-cost digital dynamometer
      for measuring isometric strength in lower limb. Eleven physically active and
      healthy participants performed maximal isometric strength for: flexion and
      extension of ankle, flexion and extension of knee, flexion, extension, adduction,
      abduction, internal and external rotation of hip. Data obtained by the digital
      dynamometer were compared with the isokinetic dynamometer to examine its
      concurrent validity. Data obtained by the digital dynamometer from 2 different
      evaluators and 2 different sessions were compared to examine its inter-rater and
      intra-rater reliability. Intra-class correlation (ICC) for validity was excellent
      in every movement (ICC > 0.9). Intra and inter-tester reliability was excellent
      for all the movements assessed (ICC > 0.75). The low-cost digital dynamometer
      demonstrated strong concurrent validity and excellent intra and inter-tester
      reliability for assessing isometric strength in the main lower limb movements.

PMID- 27882826
TI  - Investigation of the binding interaction between estazolam and bovine serum
      albumin: multi-spectroscopic methods and molecular docking technique.

PMID- 27882827
TI  - Creating a framework for data sharing in cochlear implant research.
AB  - OBJECTIVES: To summarize the development process of a national database that was
      designed to facilitate communication and collaboration, improve care, and create
      a framework for aggregate data sharing in cochlear implant (CI) research.
      METHODS: A group of nationally represented, multidisciplinary CI providers
      cooperated to define a standard set of data elements to incorporate into a
      database built by them in association with a group of computer scientists and
      software designers. CI centers across the USA, then, joined the non-profit
      Auditory Implant Initiative to use the database for their own clinical purposes
      and to help contribute to the national de-identified dataset for research and
      analytics. RESULTS: Approximately 12 months after the full release of the
      database, clinical information on 373 patients has been entered from 17 different
      CI centers representing 61 hearing professionals. A blend of six academic, seven
      private, and four non-profit CI centers participated in this phase of the data
      sharing network. DISCUSSION: The adoption of a single, standardized database by
      17 centers throughout the USA has begun a framework for data sharing in CI
      research. Future steps include (1) expanding adoption, (2) scaling the database
      to include more patients, (3) streamlining the legal hurdles required for
      adoption, and (4) integrating the database with other software platforms (e.g.
      electronic health records, processors). CONCLUSION: A standardized clinical
      outcomes database that is utilized by a growing network of CI centers can help
      strengthen research through aggregate data sharing.

PMID- 27882828
TI  - Morinda citrifolia mitigates rotenone-induced striatal neuronal loss in male
      Sprague-Dawley rats by preventing mitochondrial pathway of intrinsic apoptosis.
AB  - OBJECTIVES: Parkinson disease (PD) is a neurodegenerative disorder affecting
      mainly the motor system, as a result of death of dopaminergic neurons in the
      substantia nigra pars compacta. The present scenario of research in PD is
      directed to identify novel molecules that can be administered individually or co
      administered with L-Dopa to prevent the L-Dopa-Induced Dyskinesia (LID) like
      states that arise during chronic L-Dopa administration. Hence, in this study, we
      investigated whether Morinda citrifolia has therapeutic effects in rotenone
      induced Parkinson's disease (PD) with special reference to mitochondrial
      dysfunction mediated intrinsic apoptosis. METHODS: Male Sprague-Dawley rats were
      stereotaxically infused with rotenone (3 ug in both SNPc and VTA) and co-treated
      with the ethyl acetate extract of Morinda citrifolia and levodopa. RESULTS: The
      results revealed that rotenone-induced cell death was reduced by MCE treatment as
      measured by decline in the levels of pro-apoptotic proteins. Moreover, MCE
      treatment significantly augmented the levels of anti-apoptotic Bcl2 and blocks
      the release of cytochrome c, thereby alleviating the rotenone-induced
      dopaminergic neuronal loss, as evidenced by tyrosine hydroxylase (TH)
      immunostaining in the striatum. DISCUSSION: Taken together, the results suggest
      that Morinda citrifolia may be beneficial for the treatment of neurodegenerative
      diseases like PD.

PMID- 27882829
TI  - The effects of heat stress on a number of hematological parameters and levels of
      thyroid hormones in foundry workers.
AB  - The objective of this research was to determine the effects of heat stress on
      some hematological parameters and thyroid hormones among foundry workers. This
      study was performed on 25 heat-acclimated subjects while 10 office workers were
      selected as the control group. Wet bulb globe temperature (WBGT) was determined
      to estimate the heat stress. Blood sampling was conducted before and after the
      daily work shift. The mean value of the WBGT index was 35  degrees C. The levels
      of plasma osmolality (p = 0.04) and white blood cells (p = 0.03) in the case
      group (before exposure to heat) were significantly higher than those in control
      group. No significant differences were observed between the average levels of T3
      (p = 0.79) and T4 (p = 0.17) hormones between two groups. A positive relationship
      was found between the variation of some hematological parameters and thyroid
      hormones with WBGT index and air temperature.

PMID- 27882830
TI  - Adherence to Disease-Modifying Therapies for Multiple Sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a neurological degenerative chronic
      condition without cure. However, long-term disease-modifying therapies (DMTs)
      help reduce the severity of MS symptoms. Adherence to DMTs is key to their
      success. Several studies have analyzed what makes patients adherent to their
      DMTs. As new DMTs have entered the market, few studies have analyzed factors of
      adherence using all currently available DMTs. OBJECTIVE: To analyze different
      factors of adherence to DMTs for MS, in particular how the type of DMT affects
      adherence. METHODS: This retrospective cohort study used enrollment and claims
      data from an upper Midwest health plan in the United States between 2011 and
      2013. Patients entered the study if they had any medical claim with an MS
      diagnosis and used only 1 DMT during the study time frame. Medication possession
      ratios (MPRs) were computed as the fraction of days with medication supplied
      during the year; patients with MPRs of 0.8 or higher were considered adherent.
      Multivariate probit models with patient-specific random effects were estimated,
      with controls for demographic characteristics, type of DMT, health plan type, and
      measures of health status. RESULTS: Patients aged over 45 years were between 13.7
      to 18.6 percentage points more likely to be adherent than younger patients. Women
      had a 5.5 percentage-point lower probability of being adherent than men. Patients
      using self-injectable DMTs with injection site reactions as the most likely side
      effect were 9.1 percentage points less likely to be adherent than patients using
      oral, infusible, and other self-injectable DMTs. Patients with depression had a
      5.5 percentage-point lower probability of being adherent. These results were
      robust to changes in controls for type of plan and neighborhood socioeconomic
      characteristics. CONCLUSIONS: This study found statistically significant
      differences in adherence to DMTs by age, sex, type of DMT, and a depression
      diagnosis. DISCLOSURES: TEVA provided funding for this study and had the option
      to review the manuscript. The authors retained autonomy in the determination of
      the final content of this work. Study concept and design were contributed by
      Carlin, Anderson, and Higuera. Data interpretation was primarily performed by
      Higuera and Carlin, along with Anderson. The manuscript was written and revised
      by Higuera, Carlin, and Anderson.

PMID- 27882831
TI  - Quantifying Differences in Health Care Consumption for the Management of Multiple
      Sclerosis Within Privately and Publicly Insured Health Care Programs.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic and debilitating disease of the
      central nervous system that affects more than 570,000 persons in the United
      States and 2.3 million worldwide. Since most individuals experience initial
      symptoms between the ages of 20 and 40 years, MS can have a significant effect on
      health care consumption, quality of life, productivity, and employment over the
      long-term disease course. Opportunities exist to better understand how benefit
      design and other nonclinical factors can affect health care delivery and
      associated costs. OBJECTIVE: To observe and report variances in health care
      consumed for the treatment of MS in patients enrolled in privately (commercial)
      and publicly (Medicaid) funded health insurance programs. METHODS: In a
      retrospective analysis using Havas Gemini's proprietary MS Benchmarks Disease
      Modeling Process and IMS LifeLink Health Plan Claims and Longitudinal
      Prescriptions databases, integrated medical and pharmacy claims data were
      analyzed to select patients with a diagnosis of MS during the 2012 calendar year.
      Comorbidities were determined using ICD-9-CM codes present on medical claims.
      Prescription drug use was evaluated by pharmacy claims and drug-specific billing
      codes. RESULTS: 19,984 patients with MS were identified-18,269 from commercial
      payers and 1,715 from Medicaid. Although total annual costs related to the care
      of MS for the groups reflected a relatively small difference ($31,107 commercial;
      $33,344 Medicaid), costs associated with specific service categories varied
      greatly. Pharmacy costs were considerably less in the Medicaid group; however,
      inpatient and emergency room costs were as much as 5 times higher. Overall use of
      disease-modifying treatments (DMTs) in the Medicaid group was seen in 32.5% of
      patients and 52.1% in the commercial patient group. Thus, lower pharmacy costs in
      the Medicaid group were possibly related to lesser use of DMTs among that group
      of patients. CONCLUSIONS: This analysis illustrates that notable variances exist
      in consumption of health care resources between patients enrolled in privately
      and publicly funded health care programs. These variances may have additional
      implications relating to outcomes specific to MS. DISCLOSURES: Funding for this
      study was contributed by Biogen. The preparation, writing, revision, and approval
      of this manuscript were conducted in collaboration with Pill, who is employed by
      Havas Gemini. Livingston, Fay, and Wells are employed by and own stock in Biogen.
      Iyer was employed with Biogen at the time of the study. Study concept and design
      were contributed by Livingston, Fay, and Iyer, along with Pill and Wells.
      Livingston, Fay, and Pill collected the data, along with Iyer and Wells. Data
      interpretation was performed by Livingston, Fay, and Iyer, along with Pill and
      Wells. The manuscript was written by Livingston, Fay, and Wells, along with Pill
      and Iyer, and revised by Fay, Wells, and Pill, along with Livingston and Iyer.

PMID- 27882832
TI  - Geographic Variation in the Quality and Cost of Care for Patients with Rheumatoid
      Arthritis.
AB  - BACKGROUND: There is considerable push to improve value in health care by
      simultaneously increasing quality while lowering or containing costs. However,
      for diseases that are best treated with comparatively expensive treatments, such
      as rheumatoid arthritis (RA), there could be tension between these aims. In this
      study, we measured geographic variation in quality, access, and cost for patients
      with RA, a disease with effective but costly specialty treatments. OBJECTIVE: To
      assess the geographic differences in the quality, access, and cost of care for
      patients with RA. METHODS: Using large claims databases covering the period
      between 2008 and 2014, we measured quality of care metrics by metropolitan
      statistical areas (MSAs) for patients with RA. Quality measures included use of
      disease-modifying antirheumatic drugs (DMARDs) and tuberculosis (TB) screening
      before initiating biologic DMARD therapy. Access to care measures included
      measured detection and the share of patients with RA who visited a
      rheumatologist. Regression models were used to control for differences in patient
      demographics and health status across MSAs. RESULTS: For the 501,376 patients
      diagnosed with RA, in the average MSA 64.1% of RA patients received a DMARD, and
      29.6% of RA patients initiating a biologic DMARD appropriately received a TB
      screening. Only 17% (73/430) of MSAs comprised the top 2 Medicare Advantage star
      ratings for DMARD use. Measured detection was 0.59% (IQR = 0.47%-0.71%; CV =
      0.355) on average, and 57.6% (IQR = 48%-69%; CV = 0.341) of RA patients visited a
      rheumatologist. MSAs with the highest DMARD use spent $26,724 (in 2015 U.S.
      dollars) annually treating patients with RA, $5,428 more (P < 0.001) than low
      DMARD-use MSAs, largely because of higher pharmacy cost ($5,090 vs. $7,610, P <
      0.001). However, MSAs with higher DMARD use had lower RA-related inpatient cost
      ($1,890 vs. $2,342, P = 0.024). CONCLUSIONS: There were significant geographic
      variations in the quality of care received by patients with RA, although quality
      was poor in most areas. Fewer than 1 in 5 MSAs could be considered high quality
      based on patient DMARD use. Access to specialist care may be an issue, since just
      over half of patients with RA visited a rheumatologist annually. Efforts to
      incentivize better quality of care holds promise in terms of unlocking value for
      patients, but for some diseases, this approach may result in higher costs.
      DISCLOSURES: The research reported in this manuscript was supported by AbbVie
      through consulting fees paid to Precision Health Economics (PHE). AbbVie and PHE
      collaborated to develop the study design and protocol. AbbVie and PHE
      participated in the interpretation of data, review, and approval of the
      manuscript. Shafrin and Shim are employed by PHE. Ganguli and Sanchez Gonzalez
      are employed by AbbVie. Seabury reports consulting fees from PHE. The results
      from this study were presented in poster form at the Academy of Managed Care
      Pharmacy's 2015 Annual Meeting and Expo; April 7-10, 2015; San Diego, California,
      and at the Academy of Managed Care Pharmacy's 2016 Annual Meeting and Expo; April
      19-22, 2016; San Francisco, California. Study concept and design were contributed
      primarily by Shafrin, along with Ganguli and Seabury. Shafrin and Shim took the
      lead in data collection, and data interpretation was performed by Ganguli,
      Sanchez Gonzalez, Seabury, and Shafrin. The manuscript was written primarily by
      Shafrin, along with Shim and Seabury, and revised primarily by Ganguli, along
      with Sanchez Gonzalez and Seabury.

PMID- 27882833
TI  - Evaluation of Real-World Experience with Tofacitinib Compared with Adalimumab,
      Etanercept, and Abatacept in RA Patients with 1 Previous Biologic DMARD: Data
      from a U.S. Administrative Claims Database.
AB  - BACKGROUND: Real-world data comparing tofacitinib with biologic disease-modifying
      antirheumatic drugs (bDMARDs) are limited. OBJECTIVE: To compare characteristics,
      treatment patterns, and costs of patients with rheumatoid arthritis (RA)
      receiving tofacitinib versus the most common bDMARDs (adalimumab [ADA],
      etanercept [ETN], and abatacept [ABA]) following a single bDMARD in a U.S.
      administrative claims database. METHODS: This study was a retrospective cohort
      analysis of patients aged >= 18 years with an RA diagnosis (ICD-9-CM codes 714.0x
      714.4x; 714.81) and 1 previous bDMARD filling >= 1 tofacitinib or bDMARD claim in
      the Truven MarketScan Commercial and Medicare Supplemental claims databases
      (November 1, 2012-October 31, 2014). Monotherapy was defined as absence of
      conventional synthetic DMARDs within 90 days post-index. Persistence was
      evaluated using a 60-day gap. Adherence was assessed using proportion of days
      covered (PDC). RA-related total, pharmacy, and medical costs were evaluated in
      the 12-month pre- and post-index periods. Treatment patterns and costs were
      adjusted using linear models including a common set of clinically relevant
      variables of interest (e.g., previous RA treatments), which were assessed
      separately using t-tests and chi-squared tests. RESULTS: Overall, 392 patients
      initiated tofacitinib; 178 patients initiated ADA; 118 patients initiated ETN;
      and 191 patients initiated ABA. Tofacitinib patients were older versus ADA
      patients (P = 0.0153) and had a lower proportion of Medicare supplemental
      patients versus ABA patients (P = 0.0095). Twelve-month pre-index bDMARD use was
      greater in tofacitinib patients (77.6%) versus bDMARD cohorts (47.6%-59.6%).
      Tofacitinib patients had greater 12-month pre-index RA-related total costs versus
      bDMARD cohorts (all P < 0.0001) and greatest index use of monotherapy (P = 0.0080
      vs. ABA). A similar (all P > 0.10) proportion of patients were persistent with
      tofacitinib (42.6%) versus ADA (37.6%), ETN (42.4%), and ABA (43.5%). Mean PDC
      was 0.55 for tofacitinib versus 0.57 (ADA), 0.59 (ETN), and 0.44 (ABA; P =
      0.0003). Adjusted analyses generated similar findings to the unadjusted treatment
      patterns. Tofacitinib had lower adjusted 12-month post-index mean RA-related
      total costs ($23,568) versus ADA ($29,278; P < 0.0001), ETN ($26,885; P =
      0.0248), and ABA ($30,477; P < 0.0001). CONCLUSIONS: In this study, tofacitinib
      was more commonly used as monotherapy and yielded at least comparable persistence
      and adherence with lower adjusted mean RA-related total costs versus ADA, ETN,
      and ABA. Further analysis is warranted given the greater 12-month pre-index
      bDMARD use and RA-related costs for tofacitinib versus bDMARDs. DISCLOSURES: This
      study was sponsored by Pfizer. Harnett, Gerber, Gruben, Koenig, and Chen are
      employees and shareholders of Pfizer. Some data reported in this manuscript have
      been previously presented at the Academy of Managed Care Nexus 2015; Orlando,
      Florida; October 26-29, 2015, and was submitted in abstract form to the European
      League Against Rheumatism Congress; London, United Kingdom; June 8-11, 2016. All
      authors were involved in the conception and design of this study. Harnett and
      Gruben were involved in data collection and analysis. All authors interpreted the
      data, critically reviewed and revised the manuscript, and read and approved the
      final manuscript.

PMID- 27882834
TI  - AMCP Partnership Forum: Navigating Innovations in Diabetes Care.
AB  - : New developments that provide opportunities to enhance cost-effective diabetes
      care include advances in the pharmacologic treatment of diabetes, new drug
      delivery devices, innovations in patient management strategies, contracting
      strategies that incentivize effective interventions, and mobile health
      technologies. Payers must carefully consider the utility of these advances when
      making coverage decisions and designing benefits. To engage national stakeholders
      in a discussion about how to utilize innovations in diabetes care to optimize
      patient outcomes, the Academy of Managed Care Pharmacy organized the Partnership
      Forum on Navigating Innovations in Diabetes Care in Arlington, Virginia, on July
      19-20, 2016. The forum explored current trends and advances in diabetes
      treatments and engaged in discussions about how organizations can leverage these
      emerging options to develop strategies that improve coordination of care and
      patient outcomes, while managing limited health resources. Additionally,
      stakeholders were tasked with identifying gaps in evidence that hinder decision
      making around novel therapies and other advances that are of direct relevance to
      managed care organizations. DISCLOSURES: The AMCP Partnership Forum on Navigating
      Innovations in Diabetes Care and the development of this proceedings document
      were supported by Boehringer Ingelheim, Lilly, Dexcom, Insulet Corporation,
      Intarcia Therapeutics, and Merck.

PMID- 27882835
TI  - Health Care Costs for Patients with Heart Failure Escalate Nearly 3-Fold in Final
      Months of Life.
AB  - BACKGROUND: Heart failure (HF) is a severe chronic disease with growing
      prevalence and health care burden as well as high mortality. End-of-life cost
      data for patients with HF may inform disease and medication therapy management.
      OBJECTIVES: To (a) characterize a real-world sample of patients with HF who died;
      (b) estimate health care costs for 6 months and semiannually for 24 months,
      before death; and (c) examine associations between patient characteristics and
      predeath health care costs. METHODS: This was a retrospective study of commercial
      and Medicare Advantage with Part D (MAPD) enrollees (aged >= 18 years), using
      data from a large national health plan. Included patients had evidence of HF
      during January 1, 2009-December 31, 2013, based on >= 1 inpatient hospitalization
      or >= 2 noninpatient encounters with diagnosis code for HF and evidence of
      mortality during July 1, 2009-December 31, 2013. Demographic data, comorbidities,
      guideline-directed HF-related outpatient pharmacotherapy (HFRx), and predeath
      health care costs (all-cause and HF-related) were described. A generalized linear
      model examined associations between all-cause health care costs (months 6 and 1
      previous to death) and specific patient characteristics. RESULTS: Of 48,026
      identified patients, mean age was 77.9 years; 52.8% were female; 93.0% were MAPD
      enrolled; 92.5% had Quan-Charlson comor-bidity score >= 3; and about one quarter
      (26.0%) had no evidence of HFRx. Over the last 6 months of life, monthly all
      cause total cost increased 3.2-fold for MAPD enrollees and 2.8-fold for
      commercial enrollees, although pharmacy cost decreased slightly (0.8-fold for
      both plan types). Cumulative 6-month all-cause medical cost was $37,186 for MAPD
      enrollees and $143,363 for commercial enrollees (68.8% and 73.2% due to
      hospitalization, respectively), and cumulative HF-related medical cost was
      $20,794 for MAPD enrollees and $78,440 for commercial enrollees (88.8% and 95.3%
      due to hospitaliza-tion, respectively). Over the last 24 months, semiannual all
      cause total cost increased 3.2-fold for MAPD enrollees and 4.5-fold for
      commercial enroll-ees, although pharmacy cost increased only slightly (1.1-fold
      and 1.3-fold, respectively). Based on multivariable analysis, factors associated
      with higher risk of incurring a cost increase between month 6 and month 1 before
      death included older age (75-84 years: cost ratio [CR] = 1.33, P < 0.001; 226585
      years: CR = 1.43, P < 0.001), comorbid coronary heart disease (CR = 1.12, P =
      0.003), and no evidence of HFRx (CR = 1.48, P < 0.001). CONCLUSIONS: Patients
      with HF experienced >= 2.8-fold increase in monthly all-cause total cost over the
      last 6 months of life, which was driven by hospitalization. Although MAPD
      enrollees incurred greater cost increases, cumulative costs were higher for
      commercial enrollees. After multivariable adjustment, older age, comorbid
      coronary heart disease, and no evidence of HFRx were among factors associated
      with higher risk of cost increase over the last 6 months of life. Study findings
      provide predeath cost information that should be useful in value assessments of
      innovative HF interventions and highlight impact of HFRx on predeath health care
      costs.

PMID- 27882836
TI  - Comparison of Pharmacist and Physician Managed Annual Medicare Wellness Services.
AB  - BACKGROUND: Medicare Annual Wellness Visits (AWV) are a benefit provided for
      Medicare beneficiaries to increase focus on wellness and preventive measures.
      Pharmacists can conduct AWVs, which offers a potential avenue for outpatient
      revenue generation. PROGRAM DESCRIPTION: To compare a composite of interventions
      and screenings and revenue generated by a pharmacist with those made by a
      physician during a subsequent AWV. A report generated through the electronic
      health record was used to determine AWVs conducted by a pharmacist or 3
      participating physicians from December 2013 to March 2016, including revenue
      generated. Through electronic chart review, documentation was accessed to
      quantify and categorize the number and types of referrals, health advice,
      laboratory tests, procedures, vaccinations, and screenings that were recommended
      during each patient's AWV. OBSERVATIONS: The pharmacist performed 19 subsequent
      visits, and the 3 physicians performed 89 subsequent visits. Overall, the
      composite of interventions and screenings was significantly higher in the
      pharmacist group than the physician group (P = 0.03). More interventions were
      made in the areas of health advice (P = 0.020), vaccine recommendations (P =
      0.009), and screenings in the pharmacist group (P < 0.001). The physicians
      ordered significantly more laboratory tests per visit (P < 0.001). The pharmacist
      was reimbursed on average $105 per visit versus $99 per visit for the physicians.
      IMPLICATIONS: Pharmacist-provided AWVs are at least comparable to those provided
      by physicians and offer an additional access point for valuable services for
      Medicare beneficiaries. DISCLOSURES: There was no financial contribution to this
      study. Riche reports participation in the Speaker's Bureau for Merck and the
      Speaker's Bureau and Advisory Board for Novo Nordisk. The authors have no other
      conflicts of interest to report pertinent to this research. This data has not
      been previously published in any other location. Richie, Sewell, Malinowski,
      Jackson, and Fleming were involved in study design and manuscript
      preparation/approval. Jackson was involved in data collection, and Richie and
      Sewell were involved in data collection and data analysis. Sewell and Richie had
      full access to all the data in the study and take responsibility for the
      integrity of the data and the accuracy of the data analysis.

PMID- 27882837
TI  - Determining Multiple Sclerosis Phenotype from Electronic Medical Records.
AB  - BACKGROUND: Multiple sclerosis (MS), a central nervous system disease in which
      nerve signals are disrupted by scarring and demyelination, is classified into
      phenotypes depending on the patterns of cognitive or physical impairment
      progression: relapsing-remitting MS (RRMS), primary-progressive MS (PPMS),
      secondary-progressive MS (SPMS), or progressive-relapsing MS (PRMS). The
      phenotype is important in managing the disease and determining appropriate
      treatment. The ICD-9-CM code 340.0 is uninformative about MS phenotype, which
      increases the difficulty of studying the effects of phenotype on disease.
      OBJECTIVE: To identify MS phenotype using natural language processing (NLP)
      techniques on progress notes and other clinical text in the electronic medical
      record (EMR). METHODS: Patients with at least 2 ICD-9-CM codes for MS (340.0)
      from 1999 through 2010 were identified from nationwide EMR data in the Department
      of Veterans Affairs. Clinical experts were interviewed for possible keywords and
      phrases denoting MS phenotype in order to develop a data dictionary for NLP. For
      each patient, NLP was used to search EMR clinical notes, since the first MS
      diagnosis date for these keywords and phrases. Presence of phenotype-related
      keywords and phrases were analyzed in context to remove mentions that were
      negated (e.g., "not relapsing-remitting") or unrelated to MS (e.g., "RR" meaning
      "respiratory rate"). One thousand mentions of MS phenotype were validated, and
      all records of 150 patients were reviewed for missed mentions. RESULTS: There
      were 7,756 MS patients identified by ICD-9-CM code 340.0. MS phenotype was
      identified for 2,854 (36.8%) patients, with 1,836 (64.3%) of those having just 1
      phenotype mentioned in their EMR clinical notes: 1,118 (39.2%) RRMS, 325 (11.4%)
      PPMS, 374 (13.1%) SPMS, and 19 (0.7%) PRMS. A total of 747 patients (26.2%) had 2
      phenotypes, the most common being 459 patients (16.1%) with RRMS and SPMS. A
      total of 213 patients (7.5%) had 3 phenotypes, and 58 patients (2.0%) had 4
      phenotypes mentioned in their EMR clinical notes. Positive predictive value of
      phenotype identification was 93.8% with sensitivity of 94.0%. CONCLUSIONS:
      Phenotype was documented for slightly more than one third of MS patients, an
      important but disappointing finding that sets a limit on studying the effects of
      phenotype on MS in general. However, for cases where the phenotype was
      documented, NLP accurately identified the phenotypes. Having multiple phenotypes
      documented is consistent with disease progression. The most common
      misidentification was because of ambiguity while clinicians were trying to
      determine phenotype. This study brings attention to the need for care providers
      to document MS phenotype more consistently and provides a solution for capturing
      phenotype from clinical text. DISCLOSURES: This study was funded by Anolinx and
      F. Hoffman-La Roche. Nelson serves as a consultant for Anolinx. Kamauu is owner
      of Anolinx, which has received multiple research grants from pharmaceutical and
      biotechnology companies. LaFleur has received a Novartis grant for ongoing work.
      The views expressed in this article are those of the authors and do not
      necessarily reflect the position or policy of the Department of Veterans Affairs
      or the U.S. government. Study concept and design were contributed by Butler,
      LaFleur, Kamauu, DuVall, and Nelson. DuVall collected the data, and
      interpretation was performed by Nelson, DuVall, and Kamauu, along with Butler,
      LaFleur, and Knippenberg. The manuscript was written primarily by Nelson, along
      with Knippenberg and assisted by the other authors, and revised by Knippenberg,
      Nelson, and DuVall, along with the other authors.

PMID- 27882838
TI  - A Pragmatic Randomized Trial Comparing Telephone-Based Enhanced Pharmacy Care and
      Usual Care to Support Smoking Cessation.
AB  - BACKGROUND: Smoking is the leading preventable cause of death, and tobacco
      control professionals continue to make progress in cessation efforts. Pharmacists
      can assist smokers seeking to quit by offering counseling on smoking cessation
      pharmacotherapies. Pragmatic randomized trials are useful for investigating
      practical questions about an intervention's risks, benefits, and costs in routine
      clinical practice. OBJECTIVE: To evaluate an enhanced pharmacy care (EPC) program
      involving personalized pharmacist-provided telephone counseling for supporting
      prescription smoking cessation medications compared with usual care (UC).
      METHODS: Cigarette smokers filling a newly prescribed smoking cessation
      pharmacotherapy and with pharmacy benefits managed by Express Scripts were
      recruited. Qualified subjects were randomized 1:1 to EPC and UC. Subjects in EPC
      received 3 telephone-counseling sessions from specialist pharmacists during the
      early course of the study, while subjects in UC did not receive any counseling
      sessions. Study outcomes were collected through telephone contact and using the
      Express Scripts prescription database. The primary outcome assessed the 1-week
      point prevalence (PP) of smoking abstinence at the end of the trial (week 12).
      Secondary outcomes included 4-week PP at week 12 and adherence, evaluated by
      proportion of days covered (PDC), to prescribed smoking cessation
      pharmacotherapies. RESULTS: There were 1,017 randomized subjects. Among them,
      1,002 subjects were included in the analysis, and 513 were randomized into EPC
      and 489 into UC. Baseline demographics, smoking history, and prescribed smoking
      cessation pharmacotherapies were comparable. Varenicline and nicotine replacement
      therapy (NRT) were most frequently prescribed for smoking cessation. In EPC,
      46.0% received all 3 counseling sessions; 29.4% received 2 sessions; and 14.6%
      received 1 session. Overall, 353 subjects in EPC and 383 subjects in UC completed
      the week 12 assessment. In the analysis for 1-week PP of smoking abstinence at
      week 12, the percentage of abstainers in EPC was numerically higher than in UC
      (42.3% vs. 38.2%) with OR = 1.24, 95% CI = 0.96-1.61. It was not statistically
      significant. Adherence to prescription smoking cessation medication was
      significantly higher in EPC versus UC (49.7% vs. 45.6%; P = 0.033). CONCLUSIONS:
      This study evaluated whether a telephone-based pharmacy care program, provided by
      pharmacists and designed to support attempted quitters, improved quitting and
      increased adherence over usual care. The findings suggest that an enhanced
      program may benefit smokers by increasing prescription smoking cessation
      medication adherence. Future research should explore this program's effect on
      smokers who are compliant, based on insights on quitting provided by the post hoc
      analyses and limitations of the current study design. DISCLOSURES: This study was
      sponsored by Pfizer. Gong, Baker, Zou, Bruno, Jumadilova, and Lawrence are
      employees and stockholders of Pfizer. Wilson and Ewel are employees of United
      BioSource Corporation, which received funding from Pfizer for conducting this
      study and for the development of this manuscript. Study concept and design were
      contributed by Gong, Bruno, and Ewel, with assistance from Jumadilova, Lawrence,
      and Zou. Gong, Jumadilova, Lawrence, and Ewel collected the data. Data
      interpretation was performed by Baker, Zou, and Wilson, assisted by Gong,
      Lawrence, and Ewel. The manuscript was written by Baker, Ewel, and Gong, with
      assistance from the other authors, and revised by Baker, Wilson, Zou, and Gong,
      with assistance from Bruno and Jumadilova.

PMID- 27882839
TI  - Real-World Drug Costs of Treating Hepatitis C Genotypes 1-4 with Direct-Acting
      Antivirals: Initiating Treatment at Fibrosis 0-2 and 3-4.
AB  - BACKGROUND: Direct-acting antivirals (DAA) for the treatment of hepatitis C virus
      (HCV) have drastically improved outcomes but are also very costly. For this
      reason, priority for treatment is often given to patients with a higher fibrosis
      score at baseline by payers and providers rather than treating all eligible
      patients. Simulation studies have suggested that waiting to treat patients until
      fibrosis 3-4 may be more costly and result in worse outcomes; however, real-world
      implications are unknown. OBJECTIVE: To determine drug costs and outcomes for
      treating hepatitis C in patients with fibrosis scores of 0-2 and 3-4 at baseline
      in a real-world ambulatory care setting. METHODS: A total of 322 patients at 36
      clinical sites in Massachusetts with HCV genotype 1-4 and a prescription for at
      least 1 DAA medication between May 2011 and October 2015 were included.
      Retrospective and prospective chart reviews were completed by the primary
      investigator. Data were collected through April 2016. The primary outcome for the
      study was to determine the mean drug cost per sustained virologic response (SVR)
      achieved for patients with fibrosis scores of 0-2 and 3-4. Drug costs were
      calculated using average wholesale price and only included the cost of HCV
      medications, not for adjunctive medications, blood work, hospitalizations,
      anticipated complications, or any other projected medical costs. RESULTS: The
      mean +/- SD (median) drug cost per patient was $130,391 +/- 46,787 (113,400) and
      completed treatment duration was 15.0 +/- 8.9 (12) weeks. The mean drug cost per
      SVR was $155,662 for all patients with a mean drug cost per SVR of $122,452 and
      $178,401 for patients with fibrosis scores of 0-2 and 3-4, respectively. SVR
      rates were 83.5% (269/322) for all patients and 92.2% (107/116) and 78.6%
      (162/206) for patients with fibrosis scores of 0-2 and 3-4, respectively.
      Ledipasvir/ sofosbuvir; sofosbuvir + ribavirin; ledipasvir/sofosbuvir +
      ribavirin; sofos-buvir + interferon + ribavirin; boceprevir + interferon +
      ribavirin; sofosbu-vir + simeprevir; and telaprevir + interferon + ribavirin had
      a mean drug cost per SVR of $123,559; $153,347; $157,969; $184,800; $248,640;
      $251,550; and $373,333; respectively. CONCLUSIONS: Real-world knowledge about
      outcomes and drug costs may influence future decisions. Further studies are
      needed to evaluate emerging treatment options and to reflect changes in treatment
      guidelines. DISCLOSURES: No outside funding supported this study. The authors
      report no conflicts of interest. Data in this study were presented as a poster at
      the ASHP Midyear Clinical Meeting; New Orleans, Louisiana; December 9, 2015; at
      the Massachusetts Society of Health-System Pharmacists Annual Meeting; Newton,
      Massachusetts; April 12, 2016; and at Eastern States Conference for Pharmacy
      Residents and Preceptors; Hershey, Pennsylvania; May 2, 2016. Study concept and
      design was primarily contributed by Bach, along with Zaiken. Bach took the lead
      in data collection, data interpretation, and preparation of the manuscript, along
      with Zaiken.

PMID- 27882840
TI  - A Comparison of Health Care Resource Utilization and Costs for Patients with
      Allergic Rhinitis on Single-Product or Free-Combination Therapy of Intranasal
      Steroids and Intranasal Antihistamines.
AB  - BACKGROUND: Allergic rhinitis (AR) is a common condition that can be treated with
      a number of different therapies. Treatments such as intranasal antihistamines
      (INAs) and intranasal steroids (INSs) are widely used by AR patients. For some
      allergy sufferers, a combination of therapies, specifically an INA and an INS, is
      required to address their symptoms. A new treatment, the formulation of
      azelastine hydrochloride and fluticasone pro-pionate used as a single spray (MP
      AzeFlu), has become available for AR patients who need both types of treatment.
      In this regard, the comparison with the alternative concomitant use of INAs and
      INSs is of interest. The current study examines the health care resource
      utilization and costs for each cohort. OBJECTIVE: To examine the resource
      utilization and costs associated with AR for patients treated with MP-AzeFlu or
      concurrent therapy with single-ingredient INA and INS sprays (free-combination
      therapy). METHODS: A retrospective administrative claims study for commercially
      insured patients from a large U.S. health plan was performed. Patients with an AR
      diagnosis and a prescription claim for MP-AzeFlu or free-combination therapy
      between September 1, 2012, and September 30, 2013, were identified. Patients were
      aged at least 12 years at index date (first prescription fill for intranasal
      therapy) and were required to have 12 months pre-index and 6 months post-index of
      continuous enrollment. Health care resource utilization and costs were assessed
      for the post-index period. The cohorts were adjusted on baseline demographic and
      clinical characteristics using inverse propensity treatment weights. Other
      covariates, prescriber specialty, product switching during the post-index period,
      and pre-index total costs were included in the regression models measuring
      outcomes. One clinical characteristic of interest was the presence of asthma as
      comorbidity. A subset analysis of AR patients with asthma was also performed.
      RESULTS: All-cause-related pharmacy fills as well as pharmacy, medical, and total
      costs were significantly reduced by using MP-AzeFlu (N = 810) instead of the free
      combination of drugs (N = 726). For AR-related health care resource utilization,
      the MP-AzeFlu cohort had significantly fewer pharmacy fills than the free
      combination cohort (1.01 and 1.17, respectively; P < 0.001) with no significant
      difference in outpatient services and specialist visits (P = 0.139 and P = 0.117,
      respectively). Six-month AR-related pharmacy and total costs were significantly
      lower (P < 0.001 and P = 0.001) for the MP-AzeFlu cohort ($128 and $334,
      respectively) than the free-combination cohort ($268 and $458, respectively).
      There was no statistically significant difference in AR-related medical costs
      between the 2 cohorts (P = 0.454). For the subcohort of AR patients with asthma,
      the MP-AzeFlu cohort had lower 6-month asthma resource utilization and costs than
      the free-combination cohort. CONCLUSIONS: These findings suggest that, for AR
      patients needing INAs and INSs, the single-spray formulation MP-AzeFlu had better
      economic outcomes than for patients who rely on the free combination of these
      agents. MP-AzeFlu also appears to keep asthma-related utilization and costs down
      for those AR patients who also suffer from asthma. Potential explanations for
      these findings are explored. DISCLOSURES: This study was funded by Meda
      Pharmaceuticals. Authors were either employed by Meda Pharmaceuticals or received
      consulting fees from Meda Pharmaceuticals. Comprehensive Health Insights and
      Sedaghat received funding from Meda Pharmaceuticals as a consultant to
      participate in this study. Dufour and Caldwell-Tarr are employees of
      Comprehensive Health Insights. Harrow is currently employed by TESARO. This study
      was conceived by Harrow, Dufour, and Caldwell-Tarr. All authors contributed to
      the design of the study. Dufour took the lead in data collection, along with
      Caldwell-Tarr, and data interpretion was performed by Harrow, along with the
      other authors. Analyses were performed by Dufour. The manuscript was written and
      revised by all authors.

PMID- 27882841
TI  - Association of a Controlled Substance Scoring Algorithm with Health Care Costs
      and Hospitalizations: A Cohort Study.
AB  - BACKGROUND: Patients often misuse a combination of prescription drugs including
      opioids; however, the relationship between a controlled substance (CS) score and
      health outcomes is unknown. OBJECTIVE: To examine the association between a CS
      scoring algorithm and health care use, specifically total cost of care,
      hospitalizations, and emergency room (ER) visits. METHODS: This analysis was a
      retrospective cohort study using administrative claims data from a large U.S.
      health insurer. Included in the analysis were 999,852 members with a minimum CS
      score of 2.5 in the fourth quarter (4Q) of 2012, who were continuously enrolled
      from January 1, 2012, to December 31, 2013, and who were aged 18 years or older.
      A CS score was calculated using 4Q 2012 (3 months) prescription claims data and
      divided into 3 components: (1) number of CS claims, (2) number of unique
      pharmacies and unique prescribers, and (3) evidence of increasing CS use. The
      primary outcomes were total cost of care (pharmacy and medical costs), all-cause
      hospitalizations, and ER visits in 2013. We also quantified what a 1-point change
      in CS score meant for the primary outcomes. RESULTS: 47% of members had a CS
      score of 2.5, indicating a single CS claim, and 51% of members had a score
      between 3 and less than 12. The remaining 2% (20,858 members) had a score of 12
      or more. There was a statistically significant and consistently increasing
      association between the 4Q 2012 CS score and hospitalizations, ER visits, and
      total costs of care in 2013. A 1-point change in CS score was associated with a
      $1,488 change in total cost of care, 0.9% change in the hospitalization rate, and
      1.5% change in the ER visit rate. CONCLUSIONS: There is a linear association
      between increasing CS score and negative health outcomes. Insurers should
      consider interventions to lower member CS scores. DISCLOSURES: This study was
      funded internally by Prime Therapeutics. Starner, Qiu, and Gleason are employees
      of Prime Therapeutics, a pharmacy benefits management company. Karaca-Mandic is
      an employee of the University of Minnesota and did not receive any compensation
      related to this work. The results of this study were presented as a poster at the
      Academy of Managed Care Pharmacy's 27th Annual Meeting and Expo; San Diego,
      California; April 7-10, 2015. Study concept and design were contributed by
      Starner, Gleason, and Qiu. Qiu took the lead in data collection, assisted by
      Starner and Gleason. Data interpretation was performed by all the authors.
      Starner primarily wrote and revised the manuscript, along with the other authors.

PMID- 27882842
TI  - Activating concepts by activating experiential traces: investigations with a
      series of anagram solution tasks.
AB  - According to the experiential-simulations view of language, words automatically
      activate experiential traces that stem from the reader's interactions with their
      referents. Here, we focus on the corresponding influence in the opposite
      direction. By means of an anagram-solving task we investigated whether activating
      spatial experiential traces would activate the corresponding concepts, which in
      turn facilitates access to associated words. Participants solved anagrams of
      nouns associated with the ocean or the sky (e.g. dolphin = " dplhion" or cloud =
      " cdulo"). In six experiments we provided additional context information such as
      positional information (presenting the anagram at the top or the bottom of the
      screen), or pictorial information that either matched the ocean and sky theme or
      not, or both positional and pictorial information. Anagrams were solved faster
      when the position of the anagram was congruent with the location of the noun's
      referent in the real world, but only when presented on the background of an ocean
      sky picture. Thus, activating experiential traces indeed seems to activate
      related concepts but positional information alone is not enough to find
      facilitation in an anagram solving task. Rather what is needed is a whole set of
      traces that sufficiently narrow down the number of related concepts.

PMID- 27882843
TI  - Somatic symptom disorder treated with electroconvulsive therapy.
AB  - Somatic symptom disorder (SSD) is a challenging condition to treat with chronic
      pain, a common and disabling symptom. We present a patient who received
      electroconvulsive therapy (ECT) for SSD with significant improvement in pain and
      gastrointestinal symptoms. We also present a brief literature review of similar
      cases treated with ECT. Preliminary evidence suggests that ECT should be
      considered for treatment of SSD comorbid with major depressive disorder, when
      standard treatments fail. Further research is needed to clarify whether ECT can
      be used for SSD without associated depression.

PMID- 27882844
TI  - Effect of glycosylation on hydration behavior at the ice-binding surface of the
      Ocean Pout type III antifreeze protein: a molecular dynamics simulation.
AB  - Antifreeze proteins (AFPs), found in certain vertebrates, plants, fungi and
      bacteria have the ability to permit their survival in subzero environments by
      thermal hysteresis mechanism. However, the exact mechanism of ice growth
      inhibition is still not clearly understood. Here, four long explicit molecular
      dynamics (MD) simulations have been carried out at two different temperatures
      (277 and 298 K) with and without glycan to study the conformational rigidity of
      the Ocean pout type III antifreeze protein in aqueous medium and the structural
      arrangements of water molecules hydrating its ice-binding surface. It is found
      that irrespective of the temperature the ice-binding surface (IBS) of the protein
      is relatively more rigid than its non ice-binding surface (NonIBS) in its native
      and glycosylated form. Hydrophilic residues N14, T18 and Q44 are essential to
      antifreeze activity. Radial distribution, density distribution function and
      nearest neighbor orientation plots with respect to individual two surfaces
      confirm that density of water molecule near these binding surface in native and
      glycosylated form are relatively more than the nonbinding surface. The
      glycosylated form shows a strong peak than the native one. From rotational auto
      correlation function of water molecules around ice-binding sites, it is prominent
      that with increase in temperature, strong interaction between the water oxygen
      and the hydrogen bond acceptor group on the protein-binding surface decreases.
      This provides a possible molecular reason behind the ice-binding activity of
      ocean pout at the prism plane of ice.

PMID- 27882846
TI  - The Partington Prize 2017.

PMID- 27882845
TI  - The Englishing of Medieval Alchemy.

PMID- 27882855
TI  - No evidence for age-related differences in item-method directed forgetting of
      emotional words.
AB  - Research indicates that people can intentionally forget, but it is less clear how
      ageing and emotion interact with this ability. The present research investigated
      item-method directed forgetting of negative, neutral, and positive words in young
      (20-35 years), young-old (60-74 years), and old-old (75-89 years) adults.
      Although old-old adults showed overall reduced memory compared to young and young
      old adults, all three age groups showed intentional forgetting. Moreover,
      intentional forgetting was not affected by the valence of the word in any of the
      three age groups. These findings suggest that younger and older adults can
      intentionally forget information that is neutral or emotional in nature. The
      present study's results extend previous research by showing that this ability is
      preserved in very old age.

PMID- 27882856
TI  - Validation of semantic illusions independent of anomaly detection: evidence from
      eye movements.
AB  - Several theorists have argued that readers fail to detect semantic anomalies
      during reading, and that these effects are indicative of "shallow processing"
      behaviours. Previous studies of semantic anomalies such as the Moses illusion
      have focused primarily on explicit detection tasks. In the present study, we
      examined participants' eye movements as they read true/false statements that were
      non-anomalous, or contained a semantic anomaly that was either high- or low
      related to the correct information. Analyses of reading behaviours revealed that
      only low-related detected anomalies resulted in initial processing difficulty,
      but both detected and undetected anomalies, regardless of whether they were high-
      or low-related, resulted in delayed processing difficulty. The results extend
      previous findings on semantic anomalies and are discussed in terms of the RI-Val
      model of text processing.

PMID- 27882857
TI  - Learning from observation, feedback, and intervention in linear and non-linear
      task environments.
AB  - This multiple-cue judgment study investigates whether we can manipulate the
      judgment strategy and increase accuracy in linear and non-linear cue-criterion
      environments just by changing the training mode. Three experiments show that
      accuracy in simple linear additive task environments are improved with feedback
      training and intervention training, while accuracy in complex multiplicative
      tasks are improved with observational training. The observed interaction effect
      suggests that the training mode invites different strategies that are adjusted as
      a function of experience to the demands from the underlying cue-criterion
      structure. Thus, feedback and the intervention training modes invite cue
      abstraction, an effortful but successful strategy in combination with simple
      linear task structures, and observational training invites exemplar memory
      processes, a simple but successful strategy in combination with complex non
      linear task structures. The study discusses adaptive cognition and the
      implication of the different training modes across a life span and for clinical
      populations.

PMID- 27882858
TI  - Longitudinal associations of parental and peer influences with physical activity
      during adolescence: findings from the COMPASS study.
AB  - INTRODUCTION: To examine temporal variations in parental and peer influences on
      adolescent physical activity (PA) and whether these variations predicted changes
      in PA. METHODS: We analyzed data from Years 1, 2 and 3 of the COMPASS study.
      Participants were 22 909 students in Grades 9 to 12 (mean age [years] = 15.42 +/-
      1.12, 46% boys, 85% White), who had completed the following survey items on 2 or
      more consecutive occasions: age, sex, grade, race/ethnicity, moderate-to-vigorous
      physical activity (MVPA), parental encouragement and parental instrumental
      support for PA, and number of active peers. We used a linear-mixed model to
      investigate longitudinal effects of parental and peer influences on changes in
      square-root transformed average MVPA. We used a generalized-estimating-equations
      (GEE) model to investigate compliance with Canadian PA guidelines for youth.
      These models included parental encouragement, instrumental support and number of
      active peers as time-varying predictors, adjusting for sociodemog raphic factors
      and grade as covariates, and accounting for the clustering within children and
      schools. RESULTS: We found that adolescents perceived significantly less parental
      encouragement and instrumental support and reported fewer active peers as they
      got older. In addition, the adjusted models suggest that, for a one-unit increase
      in the score of parental encouragement, parental instrumental support and number
      of active peers, average MVPA significantly increased by 0.22 units, 0.23 units
      and 0.16 units, respectively. For the same one-unit increase, adjusted odds of an
      adolescent complying with the PA guidelines increased by 9%, 4% and 6%,
      respectively. CONCLUSION: Promoting parental support and facilitating the
      formation and maintenance of a physically active friendship network may play an
      important role in attenuating declines in PA during adolescence.

PMID- 27882860
TI  - Is child sexual abuse declining in Canada? Results from nationally representative
      retrospective surveys.
AB  - INTRODUCTION: Numerous data sources suggest a decline in child sexual abuse (CSA)
      in the United States since the early 1990s. Some evidence also indicates that an
      earlier period of higher CSA incidence began following World War II. This study
      examines prevalence estimates of sexual abuse reported retrospectively as having
      occurred in childhood (ChSA) in two nationally representative surveys of the
      Canadian population. METHODS: Data are from 13 931 respondents aged 18 to 76
      years from the 2004/2005 Canadian Gender, Alcohol, and Culture: An International
      Study (GENACIS), and from 22 169 household residents aged 18 years or older who
      participated in the 2012 Canadian Community Health Survey-Mental Health (CCHS
      MH). We present inter- and intrasurvey comparisons of ChSA prevalence specific to
      sex and age groups. RESULTS: Findings from both surveys suggest a decline in CSA
      since 1993, consistent with declines observed in the United States. Results also
      suggest that 1946 to 1992 was a period of higher risk of CSA, relative to the
      period before 1946. The evidence was more robust for women. CONCLUSION: Evidence
      of a decline in CSA in Canada since the early 1990s is encouraging, given the
      long-term debilitating effects with which it is associated. Continued monitoring
      is critical. The long-term negative effects associated with CSA underscore the
      importance of continuing to move from lower risk to zero risk.

PMID- 27882861
TI  - Status report - Public Health 2016: time for a cultural shift in the field of
      public health.
AB  - Public Health 2016, the Canadian Public Health Association's annual conference,
      was held from June 13 to 16, 2016, in Toronto, Canada, and showcased a wide
      variety of public health issues that fostered considerable discussion at the
      conference and on social media. The four plenary sessions, while on seemingly
      disparate topics including technology, violence prevention, racism and harm
      reduction, all revealed the need for a cultural shift in the field of public
      health that acknowledges and addresses the broader inequities that influence the
      health and well-being of populations. They also highlighted some of the key
      challenges that society faces in achieving the UN Sustainable Development Goals
      released in 2015.

PMID- 27882859
TI  - Suicide and self-inflicted injury hospitalizations in Canada (1979 to 2014/15).
AB  - INTRODUCTION: The purpose of this paper is to describe the trends and patterns of
      self-inflicted injuries, available from Canadian administrative data between 1979
      and 2014/15, in order to inform and improve suicide prevention efforts. METHODS:
      Suicide mortality and hospital separation data were retrieved from the Public
      Health Agency of Canada (PHAC) holdings of Statistics Canada's Canadian Vital
      Statistics: Death Database (CVS:D) (1979 to 2012); Canadian Socio-Economic
      Information Management System (CANSIM 2011, 2012); the Hospital Morbidity
      Database (HMDB) (1994/95 to 2010/11); and the Discharge Abstract Database
      (2011/12 to 2014/15). Mortality and hospitalization counts and rates were
      reported by sex, 5-year age groups and method. RESULTS: The Canadian suicide rate
      (males and females combined, all ages, age-sex standardized rate) has decreased
      from 14.4/100 000 (n = 3355) in 1979 to 10.4/100 000 (n = 3926) in 2012, with an
      annual percent change (APC) of -1.2% (95% CI: -1.3 to -1.0). However, this trend
      was not observed in both sexes: female suicide rates stabilized around 1990,
      while male rates continued declining over time-yet males still accounted for
      75.7% of all suicides in 2012. Suffocation (hanging and strangulation) was the
      primary method of suicide (46.9%) among Canadians of all ages in 2012, followed
      by poisoning at 23.3%. In the 2014/15 fiscal year, there were 13 438
      hospitalizations in Canada (excluding Quebec) associated with self-inflicted
      injuries-over 3 times the number of suicides. Over time females have displayed
      consistently higher rates of hospitalization for self-inflicted injury than
      males, with 63% of the total. Poisoning was reported as the most frequent means
      of self-inflicted harm in the fiscal year 2014/15, at 86% of all
      hospitalizations. CONCLUSION: Suicides and self-inflicted injuries continue to be
      a serious - but preventable - public health problem that requires ongoing
      surveillance.

PMID- 27882862
TI  - Milk and dairy products: good or bad for human health? An assessment of the
      totality of scientific evidence.
AB  - BACKGROUND: There is scepticism about health effects of dairy products in the
      public, which is reflected in an increasing intake of plant-based drinks, for
      example, from soy, rice, almond, or oat. OBJECTIVE: This review aimed to assess
      the scientific evidence mainly from meta-analyses of observational studies and
      randomised controlled trials, on dairy intake and risk of obesity, type 2
      diabetes, cardiovascular disease, osteoporosis, cancer, and all-cause mortality.
      RESULTS: The most recent evidence suggested that intake of milk and dairy
      products was associated with reduced risk of childhood obesity. In adults, intake
      of dairy products was shown to improve body composition and facilitate weight
      loss during energy restriction. In addition, intake of milk and dairy products
      was associated with a neutral or reduced risk of type 2 diabetes and a reduced
      risk of cardiovascular disease, particularly stroke. Furthermore, the evidence
      suggested a beneficial effect of milk and dairy intake on bone mineral density
      but no association with risk of bone fracture. Among cancers, milk and dairy
      intake was inversely associated with colorectal cancer, bladder cancer, gastric
      cancer, and breast cancer, and not associated with risk of pancreatic cancer,
      ovarian cancer, or lung cancer, while the evidence for prostate cancer risk was
      inconsistent. Finally, consumption of milk and dairy products was not associated
      with all-cause mortality. Calcium-fortified plant-based drinks have been included
      as an alternative to dairy products in the nutrition recommendations in several
      countries. However, nutritionally, cow's milk and plant-based drinks are
      completely different foods, and an evidence-based conclusion on the health value
      of the plant-based drinks requires more studies in humans. CONCLUSION: The
      totality of available scientific evidence supports that intake of milk and dairy
      products contribute to meet nutrient recommendations, and may protect against the
      most prevalent chronic diseases, whereas very few adverse effects have been
      reported.

PMID- 27882863
TI  - Porphyromonas gingivalis suppresses adaptive immunity in periodontitis,
      atherosclerosis, and Alzheimer's disease.
AB  - Porphyromonas gingivalis, a keystone pathogen in chronic periodontitis, has been
      found to associate with remote body organ inflammatory pathologies, including
      atherosclerosis and Alzheimer's disease (AD). Although P. gingivalis has a
      plethora of virulence factors, much of its pathogenicity is surprisingly related
      to the overall immunosuppression of the host. This review focuses on P.
      gingivalis aiding suppression of the host's adaptive immune system involving
      manipulation of cellular immunological responses, specifically T cells and B
      cells in periodontitis and related conditions. In periodontitis, this bacterium
      inhibits the synthesis of IL-2 and increases humoral responses. This reduces the
      inflammatory responses related to T- and B-cell activation, and subsequent IFN
      gamma secretion by a subset of T cells. The T cells further suppress upregulation
      of programmed cell death-1 (PD-1)-receptor on CD+cells and its ligand PD-L1 on
      CD11b+-subset of T cells. IL-2 downregulates genes regulated by immune response
      and induces a cytokine pattern in which the Th17 lineage is favored, thereby
      modulating the Th17/T-regulatory cell (Treg) imbalance. The suppression of IFN
      gamma-stimulated release of interferon-inducible protein-10 (IP-10) chemokine
      ligands [ITAC (CXCL11) and Mig (CXCL9)] by P. gingivalis capsular serotypes
      triggers distinct T cell responses and contributes to local immune evasion by
      release of its outer membrane vesicles. In atherosclerosis, P. gingivalis reduces
      Tregs, transforms growth factor beta-1 (TGFbeta-1), and causes imbalance in the
      Th17 lineage of the Treg population. In AD, P. gingivalis may affect the blood
      brain barrier permeability and inhibit local IFN-gamma response by preventing
      entry of immune cells into the brain. The scarcity of adaptive immune cells in AD
      neuropathology implies P. gingivalis infection of the brain likely causing
      impaired clearance of insoluble amyloid and inducing immunosuppression. By the
      effective manipulation of the armory of adaptive immune suppression through a
      plethora of virulence factors, P. gingivalis may act as a keystone organism in
      periodontitis and in related systemic diseases and other remote body inflammatory
      pathologies.

PMID- 27882864
TI  - Patient participation in palliative care decisions: An ethnographic discourse
      analysis.
AB  - The participation of patients in making decisions about their care is especially
      important towards the end of life because palliative care decisions involve
      extensive uncertainty and are heavily influenced by personal values. Yet, there
      is a scarcity of studies directly observing clinical interactions between
      palliative patients and their health care providers. In this study, we aimed to
      understand how patient participation in palliative care decisions is constructed
      through discourse in a community hospital-based palliative care team. This
      qualitative study combined ethnographic observations of a palliative care team
      with discourse analysis. Eighteen palliative care patients with cancer diagnoses,
      six family physicians, and two nurses were involved in the study. Multiple
      interactions were observed between each patient and health care providers over
      the course of 1 year, for a total of 101 consultations, 24 of which were audio
      recorded. The analysis consisted in looking for the interpretive repertoires
      (i.e., familiar lines of argument used to justify actions) that were used to
      justify patient participation in decision-making during clinical interactions, as
      well as exploring their implications for decision roles and end-of-life care.
      Patients and their health care providers seldom addressed their decision-making
      roles explicitly. Rather, they constructed patient participation in palliative
      care decisions in a covert manner. Four interpretive repertoires were used to
      justify patient participation: (1) exposing uncertainty, (2) co-constructing
      patient preferences, (3) affirming patient autonomy, and finally (4) upholding
      the authority of health care providers. The results demonstrate how patients and
      health care providers used these arguments to negotiate their respective roles in
      decision-making. In conclusion, patients and health care providers used a variety
      of interpretive repertoires to covertly negotiate their roles in decision-making,
      and to legitimize decisions that shaped patients' dying trajectories. Discourse
      analysis encourages awareness of the role of language in either promoting or
      hindering patient participation in decision-making.

PMID- 27882865
TI  - Community perceptions on domestic violence against pregnant women in Nepal: a
      qualitative study.
AB  - BACKGROUND: Globally, knowledge of health sector options to respond to domestic
      violence during pregnancy is increasing, but this topic is under-investigated in
      Nepal. This gap affects the provision of adequate antenatal care services and
      understanding of factors that influence women's willingness and ability to use
      available services. It is critical to know more about the social norms in a
      community that promote and prevent women experiencing domestic violence from
      seeking antenatal care. OBJECTIVE: To explore community perceptions of domestic
      violence against pregnant women. METHODS: A qualitative study was conducted in
      Dhulikhel municipality, involving 41 men and 76 women in 12 focus group
      discussions in different gender and family role separated groups. The interviews
      were recorded, transcribed in verbatim, and analyzed using content analysis. A
      socio-ecological model was used as a theoretical framework to illustrate linkages
      between individual, relationship, community, and societal influences on
      perceptions of domestic violence during pregnancy. RESULTS: The community
      recognized different forms of violence during pregnancy threatening women's
      physical and psychological health and presenting obstacles to seeking antenatal
      care. Some types of culturally specific violence were considered particularly
      harmful, such as pressure to give birth to sons, denial of food, and forcing
      pregnant women to do hard physical work during pregnancy, which may leave
      daughters-in-law vulnerable to domestic violence in extended families. A culture
      where violence is normalized and endurance and family reconciliation are promoted
      above individual health was perceived to cause women to tolerate and accept the
      situation. Participants suggested actions and strategies to address continuing
      violence, which indicated a societal transition toward increased awareness and
      changing attitudes and practices. CONCLUSIONS: Domestic violence during pregnancy
      needs to be addressed at different levels in Nepal, where women are often
      dependent on others for access to health care. Social norms were perceived to be
      shifting toward reduced acceptance of violence against women, but restrictions on
      women's life options, movement, and decision-making authority were still
      considered impediments to pregnant women's health.

PMID- 27882866
TI  - The performance of community health workers in the management of multiple
      childhood infectious diseases in Lira, northern Uganda - a mixed methods cross
      sectional study.
AB  - BACKGROUND: Community health workers (CHWs) have the potential to reduce child
      mortality by improving access to care, especially in remote areas. Uganda has one
      of the highest child mortality rates globally. Moreover, rural areas bear the
      highest proportion of this burden. The optimal performance of CHWs is critical.
      In this study, we assess the performance of CHWs in managing malaria, pneumonia,
      and diarrhea in the rural district of Lira, in northern Uganda. DESIGNS: A cross
      sectional mixed methods study was undertaken to investigate the performance of
      393 eligible CHWs in the Lira district of Uganda. Case scenarios were conducted
      with a medical officer observing CHWs in their management of children suspected
      of having malaria, pneumonia, or diarrhea. Performance data were collected using
      a pretested questionnaire with a checklist used by the medical officer to score
      the CHWs. The primary outcome, CHW performance, is defined as the ability to
      diagnose and treat malaria, diarrhea, and pneumonia appropriately. Participants
      were described using a three group performance score (good vs. moderate vs.
      poor). A binary measure of performance (good vs. poor) was used in multivariable
      logistic regression to show an association between good performance and a range
      of independent variables. The qualitative component comprised seven key informant
      interviews with experts who had informed knowledge with regard to the
      functionality of CHWs in Lira district. RESULTS: Overall, 347 CHWs (88.3%) had
      poor scores in managing malaria, diarrhea, and pneumonia, 26 (6.6%) had moderate
      scores, and 20 (5.1%) had good scores. The factors that were positively
      associated with performance were secondary-level education (adjusted odds ratio
      [AOR] 2.72; 95% confidence interval [CI] 1.50-4.92) and meeting with supervisors
      in the previous month (AOR 2.52; 95% CI 1.12-5.70). Those factors negatively
      associated with CHW performance included: serving 100-200 households (AOR 0.24;
      95% CI 0.12-0.50), serving more than 200 households (AOR 0.22; 95% CI 0.10-0.48),
      and an initial training duration lasting 2-3 days (AOR 0.13; 95% CI 0.04-0.41).
      The qualitative findings reinforced the quantitative results by indicating that
      refresher training, workload, and in-kind incentives were important determinants
      of performance. CONCLUSIONS: The performance of CHWs in Lira was inadequate.
      There is a need to consider pre-qualification testing before CHWs are appointed.
      Providing ongoing support and supervision, and ensuring that CHWs have at least
      secondary education can be helpful in improving their performance. Health system
      managers also need to ensure that the CHWs' workload is moderated as work
      overload will reduce performance. Finally, although short training programs are
      beneficial to some degree, they are not sufficient and should be followed up with
      regular refresher training.

PMID- 27882867
TI  - Subtyping of Cryptosporidium cuniculus and genotyping of Enterocytozoon bieneusi
      in rabbits in two farms in Heilongjiang Province, China.
AB  - Cryptosporidium spp. and Enterocytozoon bieneusi are two prevalent opportunistic
      pathogens in humans and animals. Currently, few data are available on genetic
      characterization of both pathogens in rabbits in China. The aim of the present
      study was to understand prevalence and genetic characterization of
      Cryptosporidium spp. and E. bieneusi in rabbits. We collected 215 fecal samples
      from 150 Rex rabbits and 65 New Zealand White rabbits on two different farms in
      Heilongjiang Province, China. Cryptosporidium spp. and E. bieneusi were tested by
      polymerase chain reaction (PCR) and sequencing the partial small subunit of
      ribosomal DNA (SSU rDNA) and the internal transcribed spacer (ITS) region of
      rDNA, respectively. Cryptosporidium was detected in 3.3% (5/150) of Rex rabbits
      and 29.2% (19/65) of New Zealand White rabbits. All the 24 Cryptosporidium
      isolates were identified as C. cuniculus. Enterocytozoon bieneusi was only found
      in 14.7% (22/150) of Rex rabbits. Five known genotypes: CHN-RD1 (n = 12), D (n =
      3), Type IV (n = 2), Peru6 (n = 1), and I (n = 1), and three novel ones CHN-RR1
      to CHN-RR3 (one each) were detected. By analyzing the 60-kDa glycoprotein (gp60)
      gene sequences of C. cuniculus isolates, three subtypes were obtained: VbA28 (n =
      2), VbA29 (n = 16), and VbA32 (n = 3). All these three C. cuniculus subtypes were
      reported previously in humans. Four known E. bieneusi genotypes have been found
      to be present in humans. The three novel ones fell into zoonotic group 1. The
      results suggest zoonotic potential of C. cuniculus and E. bieneusi isolates in
      rabbits.

PMID- 27882868
TI  - Seroprevalence of Toxoplasma gondii infection and risk factors in domestic sheep
      in Henan province, central China.
AB  - Sheep are highly susceptible to infections with Toxoplasma gondii and play a
      major role in the transmission of toxoplasmosis to humans. In the present study,
      779 serum samples from sheep were collected from Henan province, central China
      from March 2015 to May 2016, and antibodies to T. gondii were detected by
      modified agglutination test (MAT). The overall seroprevalence of T. gondii in
      sheep was 12.71% (99/779). The risk factors significantly associated with T.
      gondii seroprevalence were the geographical origin, age, presence of cats, and
      the rearing system. This is the first report of T. gondii infection in sheep in
      Henan province, central China, and of an association of seropositivity to T.
      gondii with risk factors.

PMID- 27882869
TI  - Aerotaxis in the closest relatives of animals.
AB  - As the closest unicellular relatives of animals, choanoflagellates serve as
      useful model organisms for understanding the evolution of animal
      multicellularity. An important factor in animal evolution was the increasing
      ocean oxygen levels in the Precambrian, which are thought to have influenced the
      emergence of complex multicellular life. As a first step in addressing these
      conditions, we study here the response of the colony-forming choanoflagellate
      Salpingoeca rosetta to oxygen gradients. Using a microfluidic device that allows
      spatio-temporal variations in oxygen concentrations, we report the discovery that
      S. rosetta displays positive aerotaxis. Analysis of the spatial population
      distributions provides evidence for logarithmic sensing of oxygen, which enhances
      sensing in low oxygen neighborhoods. Analysis of search strategy models on the
      experimental colony trajectories finds that choanoflagellate aerotaxis is
      consistent with stochastic navigation, the statistics of which are captured using
      an effective continuous version based on classical run-and-tumble chemotaxis.

PMID- 27882872
TI  - Editorial: What's new this month?

PMID- 27882871
TI  - Single synapse evaluation of the postsynaptic NMDA receptors targeted by evoked
      and spontaneous neurotransmission.
AB  - Recent studies indicate that within individual synapses spontaneous and evoked
      release processes are segregated and regulated independently. In the hippocampus,
      earlier electrophysiological recordings suggested that spontaneous and evoked
      glutamate release can activate separate groups of postsynaptic NMDA receptors
      with limited overlap. However, it is still unclear how this separation of NMDA
      receptors is distributed across individual synapses. In a previous paper (Reese
      and Kavalali, 2015) we showed that NMDA receptor mediated spontaneous
      transmission signals to the postsynaptic protein translation machinery through
      Ca2+-induced Ca2+ release. Here, we show that in rat hippocampal neurons although
      spontaneous and evoked glutamate release driven NMDA receptor mediated Ca2+
      transients often occur at the same synapse, these two signals do not show
      significant correlation or cross talk.

PMID- 27882873
TI  - sQUIZ your knowledge! Purulent painful plaques on a teenager's leg.

PMID- 27882875
TI  - sQUIZ your knowledge! Perianal ulcers in an immunocompromised patient.

PMID- 27882870
TI  - Large-scale remodeling of a repressed exon ribonucleoprotein to an exon
      definition complex active for splicing.
AB  - Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon
      definition phase of spliceosome assembly, but the assembly steps leading to an
      exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We
      found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP
      binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa
      nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an
      active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1
      modulated changes in exon RNP composition. The active early complex formed in the
      absence of PTBP1 proceeded to assemble an EDC with the eviction of hnRNP
      proteins, the late recruitment of SR proteins, and binding of the U2 snRNP. These
      results demonstrate that during early stages of splicing, exon RNP complexes are
      highly dynamic with many proteins failing to bind during PTBP1 arrest.

PMID- 27882874
TI  - An intermediate vascular tumour between kaposiform hemangioendothelioma and
      tufted angioma with regression of the skin lesion.

PMID- 27882876
TI  - Successful treatment of a cutaneous ulcer due to cholesterol crystal embolization
      with topical basic fibroblast growth factor.

PMID- 27882877
TI  - Dermpath & Clinic: Drug-induced Sweet syndrome.

PMID- 27882878
TI  - And next... Adnexa: Intraoperative dermatoscopy in the assessment of longitudinal
      melanonychia.

PMID- 27882880
TI  - Quantification of methanol in the presence of ethanol by selected ion flow tube
      mass spectrometry.
AB  - The quantification of trace compounds in alcoholic beverages is a useful means to
      both investigate the chemical basis of beverage flavor and to facilitate quality
      control during the production process. One compound of interest is methanol
      which, due to it being toxic, must not exceed regulatory limits. The analysis of
      headspace gases is a desirable means to do this since it does not require direct
      sampling of the liquid material. One established means to conduct headspace
      analysis is selected ion flow tube mass spectrometry (SIFT-MS). The high
      concentration of ethanol present in the headspace of alcoholic drinks complicates
      the analysis, however, via reacting with the precursor ions central to this
      technique. We therefore investigated whether methanol could be quantified in the
      presence of a large excess of ethanol using SIFT-MS. We found that methanol
      reacted with ionized ethanol to generate product ions that could be used to
      quantify methanol concentrations and used this technique to quantify methanol in
      beverages containing different quantities of ethanol. We conclude that SIFT-MS
      can be used to quantify trace compounds in alcoholic beverages by determining the
      relevant reaction chemistry.

PMID- 27882879
TI  - Treatment of chronic spontaneous urticaria with an inadequate response to H1
      antihistamines: an expert opinion.
AB  - Chronic spontaneous urticaria (CSU) is characterized by the sudden, continuous or
      intermittent appearance of pruritic wheals (hives), angioedema, or both for six
      weeks or more, with no known specific trigger. The international
      EAACI/GA2LEN/EDF/WAO urticaria guideline advises standard-dose, second-generation
      H1-antihistamines as first-line therapy. However, H1-antihistamine treatment
      leads to absence of symptoms in fewer than 50% of patients. Updosing of second
      generation H1-antihistamines (up to fourfold) as recommended by the
      EAACI/GA2LEN/EDF/WAO urticaria guideline as second-line therapy, can improve
      response, but many patients remain symptomatic. Definitions of response are often
      subjective and a consensus is needed regarding appropriate treatment targets.
      There is also an unmet need for biomarkers to assess CSU severity and activity
      and to predict treatment response. The EAACI/GA2LEN/EDF/WAO urticaria guideline
      recommends add-on omalizumab, ciclosporin A (CsA), or montelukast third-line
      treatment in patients with an inadequate response to high-dose H1-antihistamines.
      Omalizumab is currently the only licensed systemic biologic for use in CSU. Both
      omalizumab and CsA are effective third-line CSU treatments; montelukast appears
      to have lower efficacy in this setting. Omalizumab carries a label warning for
      anaphylaxis, although no cases of anaphylaxis were reported in the phase III
      trials of omalizumab in CSU and it is generally well tolerated in patients with
      CSU. Omalizumab arguably has a better safety profile than CsA.

PMID- 27882881
TI  - The mechanism of alkene elimination from protonated toluenesulphonamides
      generated by electrospray ionisation.
AB  - The positive ion electrospray mass spectra of a range of sulphonamides of general
      structure CH3C6H4SO2NHR1 [R1 = CnH2n+1 (n = 1-7), CnH2n-1 (n = 3, 4), C6H5,
      C6H5CH2 and C6H5CH(CH3)] and CH3C6H4SO2NR1R2 [R1, R2 = CnH2n+1 (n = 1-8)] are
      reported and discussed. The protonated sulphonamides derived from saturated
      primary and secondary aliphatic amines generally fragment to only a limited
      extent unless energised by collision. Two general fragmentations are observed:
      firstly, elimination of an alkene, CnH2n, obtained by hydrogen abstraction from
      one of the CnH2n+1 alkyl groups on nitrogen; secondly, cleavage to form
      CH3C6H4SO2+. The mechanism by which an alkene is lost has been probed by studying
      the variation of the intensity of the [M + H - CnH2n]+ signal with the structure
      of the alkyl substituent(s) on nitrogen and by monitoring the competition between
      the loss of different alkenes from protonated unsymmetrical sulphonamides in
      which two different alkyl groups are attached to nitrogen. This fragmentation is
      favoured by branching of the alkyl group at the carbon atom directly attached to
      nitrogen, thus suggesting that it involves a mechanism in which the stability of
      the cation obtained by stretching the bond connecting the nitrogen atom to the
      alkyl group is critical. This interpretation also explains the competition
      between alkene elimination and cleavage to form CH3C6H4SO2+ (and, in some cases,
      cleavage to form C6H5CH2+ or [C6H5CHCH3]+).

PMID- 27882882
TI  - Electrospray ionization-collision-induced dissociation-tandem mass spectrometry
      study of lead complexes with deprotonated nucleobases.
AB  - The complexes between the lead cation and deprotonated nucleobases (and
      deprotonated nucleosides) are studied by using electrospray ionization-collision
      induced dissociation-tandem mass spectrometry. It has been found that the
      deprotonated N9 atom is not the site of lead cation attachment. In ions [A - H +
      Pb]+ and [C - H + Pb]+, the lead cation is coordinated by the adenine N1 atom and
      cytosine  N3 atom and interaction between the lead cation and deprotonated amino
      groups seems very likely. Deprotonated thymine shows a higher affinity toward
      lead cation than deprotonated uracil. In the lead-nucleoside complexes lead
      cation interacts with a sugar moiety.

PMID- 27882883
TI  - Electrospray ionization tandem mass spectrometric study of protonated and alkali-
      cationized alpha/epsilon-hybrid peptides: differentiation of a pair of dipeptide
      positional isomers.
AB  - A new class of Boc-N-protected hybrid peptides derived from L- Ala and epsilon6
      Caa (L-Ala = L-Alanine, Caa = C-linked carboamino acid derived from D-xylose)
      have been studied by positive ion electrospray ionization (ESI) ion-trap tandem
      mass spectrometry (MS/MS). MSn spectra of protonated and alkali-cationized hybrid
      peptides produce characteristic fragmentation involving the peptide backbone, the
      tert-butyloxycarbonyl (Boc) group, and the side chain. The dipeptide positional
      isomers are differentiated by the collision-induced dissociation (CID) of the
      protonated and alkali-cationized peptides. The CID of [M + H]+ ion of Boc-NH-L
      Ala-epsilon-Caa- OCH3 (1) shows a prominent [M + H - C4H8]+ ion, which is totally
      absent for its positional isomer Boc-NH-epsilon-Caa-L-Ala-OCH3 (6), which instead
      shows significant loss of t-butanol. The formation of the [M + Cat - C4H8]+ ion
      is totally absent and [M + Cat - Boc + H]+ is prominent in the CID of the [M +
      Cat]+ ion of Boc-NH-L-Ala-epsilon-Caa- OCH3 (1), whereas the former is highly
      abundant and the latter is of low abundance for its positional isomer Boc-NH
      epsilon-Caa-L-Ala-OCH3 (6). It is observed that 'b' ions are abundant when
      oxazolone structures are formed through a five-membered cyclic transition state
      in tetra-, penta-, and hexapeptides and the cyclization process for larger 'b'
      ions led to an insignificant abundance. However, the significant 'b' ion is
      formed in epsilon,alpha-dipeptide, which may have a seven-membered substituted 2
      oxoazepanium ion structure. The MSn spectra of [M + Cat - Boc + H]+ ions of these
      peptides are found to be significantly different to those of [M + H - Boc + H]+
      ions. The CID spectra of [M + Cat - Boc + H]+ ions of peptide acids containing L
      Ala at the C-terminus show an abundant N-terminal rearrangement ion, [bn + 17 +
      Cat]+, which is absent for the peptide acids containing epsilon-Caa at the C
      terminus. Thus, the results of these hybrid peptides provide sequencing
      information, the structure of the cyclic intermediate involved in the formation
      of the rearrangement ion, and distinguish a pair of dipeptide positional isomers.

PMID- 27882884
TI  - Sequence protein identification by randomized sequence database and transcriptome
      mass spectrometry (SPIDER-TMS): from manual to automatic application of a 'de
      novo sequencing' approach.
AB  - Sequence protein identification by a randomized sequence database and
      transcriptome mass spectrometry software package has been developed at the
      University of Basilicata in Potenza (Italy) and designed to facilitate the
      determination of the amino acid sequence of a peptide as well as an unequivocal
      identification of proteins in a high-throughput manner with enormous advantages
      of time, economical resource and expertise. The software package is a valid tool
      for the automation of a de novo sequencing approach, overcoming the main limits
      and a versatile platform useful in the proteomic field for an unequivocal
      identification of proteins, starting from tandem mass spectrometry data. The
      strength of this software is that it is a user-friendly and non-statistical
      approach, so protein identification can be considered unambiguous.

PMID- 27882885
TI  - Protocol: A simple protocol for quantitative analysis of bio-oils through gas-
      chromatography/mass spectrometry.
AB  - A new and simple protocol for quantitative analysis of bio-oils using gas
      chromatography/mass spectrometry is suggested. Compounds were identified via
      their mass spectra, and then unavailable response factors were calculated with
      respect to diphenyl as the internal standard using a modified method previously
      suggested for gas chromatography with flame ionization detection. This new
      protocol was applied to the characterization of bio-oils obtained from the
      pyrolysis of woods of different sources or using different pyrolysis procedures.
      This protocol allowed evaluation of the yields of products from poplar pyrolysis
      (among 50% and 99%), while a reduced amounts of products were identified from the
      pyrolysis of cellulose (between 46% and 58%). The main product was always acetic
      acid, but it was formed in very large yields from poplar while lower yields were
      obtained from cellulose.

PMID- 27882886
TI  - Technical note: Air compared to nitrogen as nebulizing and drying gases for
      electrospray ionization mass spectrometry.
AB  - In the present study we tested the application of compressed air instead of pure
      nitrogen as the nebulizing and drying gas, and its influence on the quality of
      electrospray ionization (ESI) mass spectra. The intensities of the signals
      corresponding to protonated molecules were significantly (twice) higher when air
      was used. Inspection of signal-to-noise (S/N) ratios revealed that, in both
      cases, sensitivity was comparable. A higher ion abundance after the application
      of compressed air was followed by a higher background. Another potential risk of
      using air in the ESI source is the possibility for sample oxidation due to the
      presence of oxygen. To test this, we selected five easily oxidizing compounds to
      verify their susceptibility to oxidation. In particular, the presence of
      methionine was of interest. For all the compounds studied, no oxidation was
      observed. Amodiaquine oxidizes spontaneously in water solutions and its oxidized
      form can be detected a few hours after preparation. Direct comparison of the
      spectra where nitrogen was used with the corresponding spectra obtained when air
      was applied did not show significant differences. The only distinction was
      slightly different patterns of adducts when air was used. The difference concerns
      acetonitrile, which forms higher signals when air is the nebulizing gas. It is
      also important that the replacement of nitrogen with air does not affect
      quantitative data. The prepared calibration curves also visualize an intensity
      twice as high (independent of concentration within tested range) of the signal
      where air was applied. We have used our system continuously for three months with
      air as the nebulizing and drying gas and have not noticed any unexpected signal
      deterioration caused by additional source contamination from the air. Moreover,
      compressed air is much cheaper and easily available using oil-free compressors or
      pumps.

PMID- 27882887
TI  - Field-assisted paper spray mass spectrometry for the quantitative evaluation of
      imatinib levels in plasma.
AB  - Drug levels in patients' bloodstreams vary among individuals and consequently
      therapeutic drug monitoring (TDM) is fundamental to controlling the effective
      therapeutic range. For TDM purposes, different analytical approaches have been
      used, mainly based on immunoassay, liquid chromatography- ultraviolet, liquid
      chromatography-mass spectrometry and liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) methods. More recently a matrix-assisted laser
      desorption/ionisation method has been proposed for the determination of
      irinotecan levels in the plasma of subjects under therapy and this method has
      been cross- validated by comparison with data achieved by LC-MS/MS. However, to
      reach an effective point-of-care monitoring of plasma drug concentrations, a TDM
      platform technology for fast, accurate, low-cost assays is required. In this
      frame, recently the use of paper spray mass spectrometry, which is becoming a
      popular and widely employed MS method, has been proposed. In this paper we report
      the results obtained by the development of a paper spray-based method for
      quantitative analysis in plasma samples of imatinib, a new generation of
      anticancer drug. Preliminary experiments showed that poor sensitivity,
      reproducibility and linear response were obtained by the "classical" paper spray
      set-up. In order to achieve better results, it was thought of interest to operate
      in presence of a higher and more homogeneous electrical field. For this aim, a
      stainless steel needle connected with the high voltage power supply was mounted
      below the paper triangle. Furthermore, in order to obtain valid quantitative
      data, we analysed the role of the different equilibria participating to the
      phenomena occurring in paper spray experiments, depending either on instrumental
      parameters or on the chemical nature of analyte and solvents. A calibration curve
      was obtained by spiking plasma samples containing different amounts of imatinib
      (1) with known amounts of deuterated imatinib (1d3) as internal standard, with
      molar ratios [1]/[1d3] in the range 0.00-2.00. A quite good linearity was
      obtained (R2 = 0.975) and some experiments performed on spiked plasma samples
      with known amounts of 1 confirmed the validity of this method.

PMID- 27882889
TI  - Energy resolved tandem mass spectrometry experiments for resolution of isobaric
      compounds: a case of cis/trans isomerism.
AB  - A series of N-alkanol-N-cyclohexanol amine aryl esters cis/trans isomers that
      showed high efficacy to reverse the acquired resistance of cancer cells during
      chemotherapeutic therapy (MDR mechanism) was studied. These compounds were two
      1,4 cyclohexane cis/trans derivatives (named ELF26A and ELF26B, respectively),
      and their positional isomers (named ELF34A and ELF34B, respectively) where the
      aryl-moieties were exchanged. In order to evaluate the behaviour of these
      compounds during biological tests, a method based on liquid chromatography
      coupled with mass spectrometry (LC-MS), operating in tandem mass spectrometry
      (MS/MS) mode, was developed. A unique chromatographic method suitable to separate
      the two pairs of cis/trans isomers was not achieved and the MS/MS experiments of
      the different compounds was not always able to characterise the different
      isomers. Therefore, a system of linear equations of deconvolution analysis (LEDA)
      tool was proposed to determine the relative proportions of individual cis/trans
      isomers in the sample. Considering the pharmaceutical interest of the compounds
      under investigation, the analytical method developed was tested to be effective
      at the active concentration levels, corresponding to a concentration of ng mL-1
      of compound in a processed sample. Precision and accuracy of the LEDA algorithm
      at three levels of relative concentrations of analytes were checked, i.e. low
      level (about 25% in the mixture), mid-level (about 50% in the mixture) and high
      level (about 70% in the mixture). Evaluation of performances of the algorithm
      proved that the accuracy (between 88.3% and 99.9%) and precision (between 2.0%
      and 3.7%) for simultaneous analysis of the mixtures of the four isomers is
      feasible. It is worth highlighting that the choice of characteristic product ions
      and optimal abundance ratios plays an important role in the application of the
      LEDA approach. Therefore, performing an investigation on the energetics of
      fragmentation pathway allowed the selection of the better product ions for each
      analyte in terms of both sensitivity of detection and specificity, i.e. the
      capability to distinguish between isomeric compounds. Finally, the developed
      approach was applied to determine the relative proportions of individual
      cis/trans isomers in spiked human plasma samples. The results obtained confirm
      the reliability of the proposed method in biological samples as well.

PMID- 27882888
TI  - Comparison of two freely available software packages for mass spectrometry
      imaging data analysis using brains from morphine addicted rats.
AB  - Data analysis from mass spectrometry imaging (MSI) imaging experiments is a very
      complex task. Most of the software packages devoted to this purpose are designed
      by the mass spectrometer manufacturers and, thus, are not freely available.
      Laboratories developing their own MS-imaging sources usually do not have access
      to the commercial software, and they must rely on the freely available programs.
      The most recognized ones are BioMap, developed by Novartis under Interactive Data
      Language (IDL), and Datacube, developed by the Dutch Foundation for Fundamental
      Research of Matter (FOM-Amolf). These two systems were used here for the analysis
      of images received from rat brain tissues subjected to morphine influence and
      their capabilities were compared in terms of ease of use and the quality of
      obtained results.

PMID- 27882890
TI  - Determination of conditional stability constants for phytic acid complexes with
      Mg2+, Ca2+ and Zn2+ ions using electrospray ionization mass spectrometry.
AB  - The electrospray ionization mass spectrometry competitive method has been used
      for the determination of the conditional stability constants of phytic acid
      complexes with Mg2+, Ca2+ and Zn2+ ions. The competing complexation between
      ethylenediaminetetraacetic acid (EDTA) and phytic acid was studied. For EDTA
      complexes with Mg2+, Ca2+ and Zn2+ ions, the values of the conditional stability
      constants are known and were used for the calculation of this constant for the
      phytic acid complexes. The values obtained are in agreement with the literature
      data. The method applied permitted a fast and simple determination of conditional
      stability constants by measuring the response of the ionized coordination
      complexes.

PMID- 27882891
TI  - A comparative mass spectrometric study of fatty acids and metals in some seed
      extracts.
AB  - A major cause of cardiovascular diseases and cancer is diet content, so the
      optimization of micronutrients in food is very important. Omega-3 fatty acids
      supplementation for patients had beneficial effects on subjective global
      assessment score and metabolic profiles. Fatty acids content and the metal ions
      in different seeds (e.g. linseed, poppy, grape, hemp, nuts, pumpkin, sesame,
      watermelon, chia) recommended as food supplements, purchased on the Romanian
      market, were compared. Gas chromatography coupled to mass spectrometry (GC-MS)
      was used as an excellent technique for fatty acids identification and
      quantitation, and inductively coupled plasma mass spectrometer (ICP-MS) for
      analytical measurements of metals.

PMID- 27882893
TI  - Protocol: MYTHBUSTERS: a universal procedure for sample preparation for mass
      spectrometry.
AB  - Improvements in proteomic strategies from the development of new and robust
      separation and identification techniques have led to broad applications of
      proteomics to solve numerous biological questions. For all analyses, sample
      quality is unquestionably a critical factor; therefore protein extraction is of
      outmost importance. The ideal extraction method should provide reproducible
      spectra of the most comprehensive repertoire of proteins, while minimizing sample
      loss and degradation. It is already known that to capture the whole proteome is
      an unenforceable task. Many protein extraction protocols have been described, yet
      there is no "one perfect procedure" taking into account the vast diversity of
      biological and physical properties of proteins, including their charge, size,
      hydrophobicity, interactions and sub-cellular localization. The research
      presented here reflects the main obstacle occurring in proteomic experimental
      design; i.e. the lack of reproducibility as a result of alterations in protein
      extraction methods. We have performed a series of experiments, aimed towards
      identification of the aptamer-binding partners in cancerous cells. Aptamers are
      chemically synthesized, short, single-stranded nucleic acids with a strictly
      defined three-dimensional structure, which allows them to interact with a target
      molecule with high affinity. The low immunogenicity and cellular- targeting
      properties of aptamers might facilitate design of suitable drugs with low side
      effects. Aptamers can be used for identification of molecules associated with a
      pathogenic state of a cell. Aptamers can be considered as a powerful tool, since
      they possess unique properties to benefit cancer diagnosis, prevention and
      treatment. We have used different types of protein extraction methods prior to
      analyses of complex biological samples by mass spectrometry, based on slight
      changes of homogenization buffers, and have observed the changes in the
      identified compounds. These results should prove to be very useful for future
      proteomic studies and the design of studies in terms of sample preparation,
      especially sample homogenization and protein extraction.

PMID- 27882892
TI  - Automated online solid-phase extraction-liquid chromatography mass spectrometric
      analysis of dithianon in water.
AB  - An automated online solid-phase extraction-liquid chromatography mass
      spectrometry (SPE-LC/MS) method was developed for the quantification of dithianon
      in surface water samples, using warfarin as internal standard. The method was
      developed on a liquid chromatography (LC) system with Flexible Cube interfaced to
      a quadrupole time-of-flight (Q-TOF) mass spectrometer. A small volume of
      acidified water (1 mL) was spiked with internal standard, pre-concentrated online
      on polymeric cartridges and analyzed by full-scan MS in high-resolution
      conditions. The quantitative data were obtained by [M]-* of dithianon and [M - H]
      of warfarin, used as internal standard. The chromatographic separation was
      performed on a C18 column with a gradient mobile phase consisting of acetonitrile
      and water containing 0.05% acetic acid. The method was validated to measure
      concentrations of dithianon in the range of 0.010-4 ug L-1 in surface water
      samples. Twenty real water samples, collected from Torrente Novella, Val di Non
      (TN, Northern Italy), during fungicide treatments of large apple orchards, were
      analyzed. All samples were kept in glass bottles and stored in the lab at -20
      degrees C until analysis. It was found that in all samples dithianon was
      undetectable: if it is present, its concentration was lower than the limit of
      detection (LOD) (0.008 ug L-1.To investigate the stability of dithianon, a series
      of water samples were spiked at different concentrations and analyzed after
      different storage conditions. Results suggested that dithianon is not stable in
      water stored at -20 degrees C at neutral or basic pH, but the addition of acetic
      acid to pH = 3.5 increases its stability to at least two weeks.

PMID- 27882895
TI  - Planar maneuvering control of underwater snake robots using virtual holonomic
      constraints.
AB  - This paper investigates the problem of planar maneuvering control for bio
      inspired underwater snake robots that are exposed to unknown ocean currents. The
      control objective is to make a neutrally buoyant snake robot which is subject to
      hydrodynamic forces and ocean currents converge to a desired planar path and
      traverse the path with a desired velocity. The proposed feedback control strategy
      enforces virtual constraints which encode biologically inspired gaits on the
      snake robot configuration. The virtual constraints, parametrized by states of
      dynamic compensators, are used to regulate the orientation and forward speed of
      the snake robot. A two-state ocean current observer based on relative velocity
      sensors is proposed. It enables the robot to follow the path in the presence of
      unknown constant ocean currents. The efficacy of the proposed control algorithm
      for several biologically inspired gaits is verified both in simulations for
      different path geometries and in experiments.

PMID- 27882894
TI  - Electrospray ionization in the study of the interactions between cytotoxic
      phosphino Cu(I) complexes and selected amino acids and GlyGlyHis peptide model.
AB  - Tetrahedral [Cu(P)4][BF4]-type complexes (P = tertiary phosphine) are a class of
      monopositively charged compounds that have shown notable antitumor activity in
      both in vitro and in vivo tests. This biological property appears to be related
      to the peculiar physicochemical characteristics of these compounds. Although
      thermodynamically stable, they are labile at micromolar concentrations. Such a
      behavior allows the Cu(I) ion in [Cu(P)n]+ assemblies (n < 4) to interact with
      surrounding molecules, including the rich peptide/protein environment that metal
      complexes have to face in the physiological milieu on the way to tumor cells. The
      scope of this investigation was to study the interaction products that originate
      from the treatment in water/methanol mixtures of representative phosphino Cu(I)
      compounds with an excess of individual amino acids (AAs) selected on the basis of
      the donor atom likely involved in metal coordination (i.e. O-glycine, S
      methionine and N-histidine). These interactions have been investigated in
      electrospray ionization mass spectrometry (ESI-MS), mainly in the positive ion
      mode [ESI(+)MS], and the interaction products have been characterized by
      sequential collisional experiments, performed by an ion trap instrument.
      Histidine and methionine, but not glycine, were able to mine Cu(I) from [Cu(P)n]+
      assemblies through the formation of mixed [CuI(P)(AA)]+ and eventually
      [CuI(AA)2]+ adducts. The ability to substitute phosphine(s) by AAs and the
      strongest affinity for Cu(I) was proved by the study of the energetics of
      collisional-induced decomposition (CID) reactions [CuI(P)(AA)]+ -> CuI(AA) + P]+.
      Among the investigated AAs, histidine displayed the strongest affinity for Cu(I).
      Transchelation of Cu(I) was similarly observed when [Cu(P)n]+ species were
      treated with the model tripeptide GlyGlyHis (GGH), the most investigated member
      of the amino terminal Cu(II) and Ni(II) (ATCUN) peptide family. GGH was able to
      form robust metal adducts not only with Cu(II) and the related divalent Zn(II)
      and Ni(II) ions, but also with monovalent ions, including Cu(I) and Ag(I). CID
      pathways of [CuI(GGH)]+ and [AgI(GGH)]+ were qualitatively superimposable and
      proceeded through losses of neutral fragments. Similar losses of neutral
      fragments were observed from [ZnII(GGH)] and [NiII(GGH)]. CID pathways of
      [CuII(GGH)]-/+ adducts instead took place mainly through intramolecular electron
      transfer reactions comprising the reduction of Cu(II) to Cu(I) and the formation
      of fragment radical cations.

PMID- 27882896
TI  - Optical response of a line node semimetal.
AB  - We calculate the AC optical response of a line node semimetal with emphasis on
      characteristic behaviours which can be used to distinguish them from point node
      materials such as Dirac and Weyl semimetals. The interband optical background at
      zero temperature displays a flat region at small photon energies ([Formula: see
      text]) analogue to the universal background seen in graphene. However, in
      contrast to graphene, the height of the constant region is not universal but
      depends inversely on the Fermi velocity of the charge carriers and directly on
      the radius (b) in momentum space of the nodal circle. The parameter b is a
      defining energy scale and determines the range of photon energy over which the
      flat response persists. At high energies [Formula: see text], the interband
      response becomes linear in [Formula: see text] in agreement with the case for 3D
      Dirac fermions with point node. The optical spectral weight contained in the
      interband or Drude conductivity shows the same two distinct regimes. At low
      temperature (T) (chemical potential (MU)), it rises linearly with [Formula: see
      text] and is proportional to b. At high temperature, [Formula: see text], a
      [Formula: see text] law is obtained, which is independent of b. At T  =  0, the
      Lorentz number takes on the conventional value [Formula: see text] for all values
      of MU. It increases with increasing temperature to reach a first plateau of 2.4L
      o provided [Formula: see text] but [Formula: see text]. At high temperature, T  >
      b, a second plateau of height 4.2L o emerges. The first plateau is
      characteristic of 2D-Dirac while the second corresponds to 3D-Dirac. The
      thermopower as a function of temperature also shows an evolution from a 2D to 3D
      behaviour.

PMID- 27882897
TI  - Progressive freezing of interacting spins in isolated finite magnetic ensembles.
AB  - Self-organization of magnetic nanoparticles into secondary nanostructures
      provides an innovative way for designing functional nanomaterials with novel
      properties, different from the constituent primary nanoparticles as well as their
      bulk counterparts. Collective magnetic properties of such complex closed packing
      of magnetic nanoparticles makes them more appealing than the individual magnetic
      nanoparticles in many technological applications. This work reports the
      collective magnetic behaviour of magnetic ensembles comprising of single domain
      Fe3O4 nanoparticles. The present work reveals that the ensemble formation is
      based on the re-orientation and attachment of the nanoparticles in an iso
      oriented fashion at the mesoscale regime. Comprehensive dc magnetic measurements
      show the prevalence of strong interparticle interactions in the ensembles. Due to
      the close range organization of primary Fe3O4 nanoparticles in the ensemble, the
      spins of the individual nanoparticles interact through dipolar interactions as
      realized from remnant magnetization measurements. Signature of super spin glass
      like behaviour in the ensembles is observed in the memory studies carried out in
      field cooled conditions. Progressive freezing of spins in the ensembles is
      corroborated from the Vogel-Fulcher fit of the susceptibility data. Dynamic
      scaling of relaxation reasserted slow spin dynamics substantiating cluster spin
      glass like behaviour in the ensembles.

PMID- 27882898
TI  - Unique magnetic and thermoelectric properties of chemically functionalized narrow
      carbon polymers.
AB  - We analyze magnetic, transport and thermoelectric properties of narrow carbon
      polymers, which are chemically functionalized with nitroxide groups. Numerical
      calculations of the electronic band structure and the corresponding transmission
      function are based on density functional theory. Transport and thermoelectric
      parameters are calculated in the linear response regime, with particular interest
      in charge and spin thermopowers (charge and spin Seebeck effects). Such
      nanoribbons are shown to have thermoelectric properties described by large
      thermoelectric efficiency, which makes these materials promising from the
      application point of view.

PMID- 27882900
TI  - Concentration dependence of hydrogen diffusion in clamped vanadium (0 0 1) films.
AB  - The chemical diffusion coefficient of hydrogen in a 50 nm thin film of vanadium
      (0 0 1) is measured as a function of concentration and temperature, well above
      the known phase boundaries. Arrhenius analysis of the tracer diffusion constants
      reveal large changes in the activation energy with concentration: from 0.10 at
      0.05 in H V-1 to 0.5 eV at 0.2 in H V-1. The results are consistent with a change
      from tetrahedral to octahedral site occupancy, in that concentration range. The
      change in site occupancy is argued to be caused by the uniaxial expansion of the
      film originating from the combined hydrogen induced expansion and the clamping of
      the film to the substrate.

PMID- 27882899
TI  - An ab initio investigation of Bi2Se3 topological insulator deposited on amorphous
      SiO2.
AB  - We use first-principles simulations to investigate the topological properties of
      Bi2Se3 thin films deposited on amorphous SiO2, Bi2Se3/a-SiO2, which is a
      promising substrate for topological insulator (TI) based device applications. The
      Bi2Se3 films are bonded to a-SiO2 mediated by van der Waals interactions. Upon
      interaction with the substrate, the Bi2Se3 topological surface and interface
      states remain present, however the degeneracy between the Dirac-like cones is
      broken. The energy separation between the two Dirac-like cones increases with the
      number of Bi2Se3 quintuple layers (QLs) deposited on the substrate. Such a
      degeneracy breaking is caused by (i) charge transfer from the TI to the substrate
      and charge redistribution along the Bi2Se3 QLs, and (ii) by deformation of the QL
      in contact with the a-SiO2 substrate. We also investigate the role played by
      oxygen vacancies ([Formula: see text]) on the a-SiO2, which increases the energy
      splitting between the two Dirac-like cones. Finally, by mapping the electronic
      structure of Bi2Se3/a-SiO2, we found that the a-SiO2 surface states, even upon
      the presence of [Formula: see text], play a minor role on gating the electronic
      transport properties of Bi2Se3.

PMID- 27882901
TI  - Tetragonal to triclinic structural transition in the prototypical CeScSi induced
      by a two-step magnetic ordering: a temperature-dependent neutron diffraction
      study of CeScSi, CeScGe and LaScSi.
AB  - An investigation on the ground state magnetism of CeScSi, CeScGe (tetragonal
      CeScSi-type, tI12, space group I4/mmm) by temperature-dependent powder neutron
      diffraction has been carried out, as debated and controversial data regarding the
      low temperature magnetic behaviours of these two compounds were reported. Our
      studies reveal that, while cooling, long-range magnetic ordering in CeScSi and
      CeScGe takes place by a two-step process. A first transition leads to a magnetic
      structure with the Ce moments aligned ferromagnetically onto two neighbouring
      tetragonal basal a-b planes of the CeScSi-type structure; the double layers are
      then antiferromagnetically coupled to each other along the c-axis. The transition
      temperature associated with the first ordering is T N ~ 26 K and T N ~ 48 K for
      the silicide and the germanide, respectively. Here the spin directions are
      rigorously confined to the basal plane, with values of the Ce magnetic moments of
      MU Ce  =  0.8-1.0 MU B. A second magnetic transition, which takes place at
      slightly lower temperatures, results in a canting of the ordered magnetic moments
      out of the basal plane which is accompanied by an increase of the magnetic moment
      value of Ce to MU Ce  =  1.4-1.5 MU B. Interestingly, the second magnetic
      transition leads to a structural distortion in both compounds from the higher
      symmetry tetragonal space group I4/mmm to the lower-symmetry and triclinic I-1
      (non-standard triclinic). Magnetic symmetry analysis shows that the canted
      structure would not be allowed in the I4/mmm space group; this result further
      confirms the structural transition. The transition temperatures T S from I4/mmm
      to I-1 are about 22 K in CeScSi and 36 K in CeScGe, i.e. well below the
      temperature of the first onset of antiferromagnetic order observed in this work
      (or below the ordering temperature, previously reported as either T C or T N).
      This result, along with the synchronism of the magnetic and structural
      transitions, suggests a magnetostructural origin of this structural distortion.
      We have also carried out powder neutron diffraction for LaScSi as a non
      magnetically-ordering reference compound and compared the results with those of
      CeScSi and CeScGe compounds.

PMID- 27882902
TI  - Observation of the flexoelectricity of a SrTiO3 single crystal by x-ray
      absorption and emission spectroscopies.
AB  - Flexoelectricity, defined as the spontaneous electric polarization in a
      dielectric material induced by a strain gradient, is investigated from the
      microscopic viewpoint by x-ray spectroscopy. A single crystal SrTiO3 sample was
      used as a test system in order to reveal the appearance of the electric dipole
      moment by simple bending of the crystal. The spectral change characteristic of
      ferroelectric transition in SrTiO3 was not observed in the Ti K-edge absorption
      spectra. Instead, the gradual decrease (increase) of the post-edge feature (pre
      edge structure) by bending was qualitatively explained using theoretical
      calculations that assumed the presence of oxygen vacancies and a slight crystal
      distortion. This assumption is also supported by the broadening of a tiny charge
      transfer peak in the Ti Kbeta resonant emission spectra. Therefore, it was
      revealed that the flexoelectric effect in SrTiO3 is easily drowned out through
      local imperfection induced by crystal deformations and cracks.

PMID- 27882903
TI  - Results of hemihypoglossal-facial nerve anastomosis in the treatment of facial
      nerve paralysis after failed stereotactic radiosurgery for vestibular schwannoma.
AB  - Vestibular schwannoma treatment with stereotactic radiosurgery (SRS) carries a
      risk of facial nerve (CNVII) palsy that is lower than that with
      microneurosurgery. The results of hemihypoglossal-facial nerve anastomosis (HHFA)
      have not been described yet in CNVII palsy after failed stereotactic radiosurgery
      (SRS). Here we report a case series of the first four consecutive patients (three
      women; average age 58.5, age range: 46-74), who underwent HHFA due to failed SRS.
      All patients were admitted because of progressive peripheral facial nerve palsy.
      Three patients received retrosigmoid craniotomy due to tumor enlargement that
      resulted in facial nerve paralysis. All patients achieved satisfactory (House
      Brackmann grade III) CNVII regeneration. No or minimal tongue atrophy occurred on
      the side of the anastomosis. Patients reported no problems with phonation or
      swallowing, except for the patients with preexisting lower cranial nerve
      deficits. HHFA effectively treats facial palsy after failed SRS with minimal risk
      of tongue atrophy and minimal morbidity. The results of the treatment are
      comparable to those achieved with patients without previous SRS.

PMID- 27882904
TI  - Neuroendoscopic diagnosis and clinical management of cryptococcal choroid
      plexitis in an immunocompetent pregnant woman.

PMID- 27882905
TI  - A familial incidence of L1-L2 disc herniation.

PMID- 27882906
TI  - Vertebral fracture due to a solitary bone cyst.

PMID- 27882907
TI  - Practice, science and governance in interaction: European effort for the system
      wide implementation of the International Classification of Functioning,
      Disability and Health (ICF) in Physical and Rehabilitation Medicine.
AB  - Since its launch in 2001, relevant international, regional and national PRM
      bodies have aimed to implement the International Classification of Functioning,
      Disability and Health (ICF) in Physical and Rehabilitation Medicine (PRM),
      whereby contributing to the development of suitable practical tools. These tools
      are available for implementing the ICF in day-to-day clinical practice,
      standardized reporting of functioning outcomes in quality management and
      research, and guiding evidence-informed policy. Educational efforts have
      reinforced PRM physicians' and other rehabilitation professionals' ICF knowledge,
      and numerous implementation projects have explored how the ICF is applied in
      clinical practice, research and policy. Largely lacking though is the system-wide
      implementation of ICF in day-to-day practice across all rehabilitation services
      of national health systems. In Europe, system-wide implementation of ICF requires
      the interaction between practice, science and governance. Considering its
      mandate, the UEMS PRM Section and Board have decided to lead a European effort
      towards system-wide ICF implementation in PRM, rehabilitation and health care at
      large, in interaction with governments, non-governmental actors and the private
      sector, and aligned with ISPRM's collaboration plan with WHO. In this paper we
      present the current PRM internal and external policy agenda towards system-wide
      ICF implementation and the corresponding implementation action plan, while
      highlighting priority action steps - promotion of ICF-based standardized
      reporting in national quality management and assurance programs, development of
      unambiguous rehabilitation service descriptions using the International
      Classification System for Service Organization in Health-related Rehabilitation,
      development of Clinical Assessment Schedules, qualitative linkage and
      quantitative mapping of data to the ICF, and the cultural adaptation of the ICF
      Clinical Data Collection Tool in European languages.

PMID- 27882909
TI  - European initiative for the application of the International Classification of
      Functioning, Disability and Health: development of Clinical Assessment Schedules
      for specified rehabilitation services.
AB  - BACKGROUND: Clinical assessment schedule (CLAS) is a core part of the ICF-based
      implementation of functioning reporting across health conditions and along the
      continuum of care. AIM: The Physical and Rehabilitation Medicine Section and
      Board of the European Union of Medical Specialists (UEMS PRM) workshop held in
      January 2016 aimed to develop and specify a CLAS within the context of
      rehabilitation services. SETTING: UEMS PRM Workshop in Nottwil, Switzerland,
      January 2016. POPULATION: PRM physicians representatives from 12 European
      countries, as well as Israel and Japan, mostly delegates of UEMS PRM Section and
      Board, and experts with other rehabilitation professional backgrounds. METHODS:
      Participants were divided into 6 working groups and asked to specify what
      functioning aspects would be essential to document using the available ICF sets
      for the identified rehabilitation services contained in the newly developed
      service classification (ICSO-R): acute, post-acute and long-term rehabilitation
      services. RESULTS: The 7 ICF Generic and 23 Rehabilitation Set categories were
      confirmed as well as specific health condition categories for acute
      rehabilitation services (mobile team), for postacute rehabilitation services
      (general outpatient rehabilitation, musculoskeletal and neurological
      rehabilitation, as well as specialized SCI rehabilitation), and for long-term
      rehabilitation services (day clinic and rehabilitation provided in the
      community). While general principles of the CLAS were defined, the need to align
      the CLAS for a specific service, as well as across services along the continuum
      of care was highlighted. All groups deliberated on this topic; however, no
      conclusive statement was presented yet. CONCLUSIONS: The groups recognized a need
      for a systematic effort to identify data collection tools currently used.
      CLINICAL REHABILITATION IMPACT: CLASs will serve in the future to ensure that
      functioning information is systematically and consistently collected across
      services, and thus respond also to various global reports and initiatives which
      stress the need for improving data collection on people's functioning.

PMID- 27882910
TI  - Does Nintendo Wii Balance Board improve standing balance? A randomized controlled
      trial in children with cerebral palsy.
AB  - BACKGROUND: Evidence on the effect of systemic exercise programs to improve the
      standing balance with the Nintendo Wii system is very limited and its post
      treatment effectiveness is unknown in cerebral palsy (CP) patients. AIM: Primary
      aim was to compare the effect of Nintendo Wii balance board (Wii-therapy) and
      standard physiotherapy (SPT), on the performance of standing balance in children
      and adolescents with CP. Secondary aim was to determine the post-treatment
      effectiveness of Wii-therapy and SPT. DESIGN: Two-arm, matched-pairs, parallel
      groups, randomized, controlled clinical trial. SETTING: Outpatient Rehabilitation
      Centre in the city of Talca. POPULATION: Patients with CP type spastic hemiplegia
      (SHE) and spastic diplegia (SDI), aged 7 to 14 years, and level I or II of GMFCS
      or GMFCS-ER. Were excluded patients with FSIQ<80, epilepsy, previous surgeries
      and application of Botulinum Toxin-A in the lower limb, uncorrected vision and
      hearing disorders. METHODS: Thirty-two CP patients (10.7+/-3.2 years old) were
      randomly assigned to either Wii-therapy (SDI=7; SHE=9) or SPT intervention
      (SDI=7; SHE=9). In each group, patients received three sessions per week over a
      period of 6 weeks. Standing balance was assessed at baseline and every 2 weeks.
      Additionally, two follow-up assessments (4 additional weeks) were performed to
      determine post-treatment effectiveness. Standing balance was quantified on force
      platform obtaining the outcomes area of center-of-pressure (CoP) sway (CoPSway),
      standard deviation in the medial-lateral (SDML) and the anterior-posterior (SDAP)
      directions, and velocity in both directions (VML and VAP). RESULTS: Compared to
      SPT, Wii-therapy significantly reduced the CoPSway (P=0.02) and SDAP in the eyes
      open condition (P=0.01). However, the effects wane after 2-4 weeks. Post-hoc
      analysis revealed that only SHE children benefited from Wii-therapy. CONCLUSIONS:
      Wii-therapy was better than SPT in improving standing balance in patients with
      CP, but improves the balance only in SHE patients. Also, Wii-therapy
      effectiveness waned 2-4 weeks after the end the intervention. CLINICAL
      REHABILITATION IMPACT: A systematic exercise program like Wii-therapy using the
      Nintendo Wii Balance Board device can be considered to improves the standing
      balance in patients with CP, specifically in the SHE type. This program is easy
      to transfer to physiotherapists and rehabilitation centers.

PMID- 27882911
TI  - Methodological notes on applying the International Classification of Functioning,
      Disability and Health in rehabilitation.

PMID- 27882912
TI  - Does the use of a hybrid theatre in vascular surgery result in improved clinical
      outcomes and radiation protection?

PMID- 27882913
TI  - Persistent sciatic artery aneurysm: a potential cause of acute lower limb
      ischemia in young patients.

PMID- 27882914
TI  - Propulsive limb coordination and body acceleration in sprint breaststroke
      swimming.
AB  - BACKGROUND: This work aimed at examining how coordination and kinematic indices
      interplay with swimming performance measured by average speed in 50 m all-out
      test. METHODS: The group of 34 male competitive swimmers (19.1+/-1.91 years old)
      participated in the study. The underwater movements of swimmers' bodies were
      recorded providing side-shots. Accelerations and angular velocity of pitch
      rotation of swimmer's sacrum were measured with inertial sensor device (three
      axial accelerometer and gyroscope). RESULTS: Indices calculated on the basis of
      video analysis as well as their relationship with speed (V50surface breast)
      clearly show, that stroke rate (SR) kinematic and ample arm propulsion (AP)
      duration impulse are both highly associated with performance. At the same time
      V50surface breast is highly related to significant shortening inter-cycle gap -
      Glide or Overlap. The study shows, that sagittal maximal ventral acceleration
      (Azmax) and sagittal amplitude acceleration (Azamp) significantly interplay with
      V50surface breast (0.54, P<0.01 and 0.45, P=0.01 respectively), which is
      connected with dolphin-like body waving. CONCLUSIONS: The most important thing is
      to recognize possible gains coming from suitably shaped dolphin-like body waving,
      as well as to enhance this specific action during well-timed upper trunk and head
      immersion in each sprint breaststroke cycle.

PMID- 27882916
TI  - Spirometry improvement after muscular exercise in elite swimmers.
AB  - BACKGROUND: An increased sympathetic activity during muscular effort is a well
      established physiological response, whose intensity is known to increase with the
      muscular load. Spirometry was described to improve as an effect of swimming
      training in healthy and asthmatic subjects, suggesting a decrease in airway
      resistance The aim was to investigate the possible effect of muscular exercise
      (swimming) on spirometry, in particular searching for possible differences
      because of different swimming times. METHODS: The measurements were performed on
      9 highly trained male competitive swimmers (age: 41+/-12.79 years, height: 1.69+/
      0.06 meters, weight: 66.14+/-14.28 kg, BMI: 22.8+/-3.61 kg/m2) during an official
      competition. The data were collected at the border of the swimming-pool before
      (control, C) and few minutes after the swimming sessions (exercise, E), which
      consisted either of 800 meter (7 subjects) or 1500 meter (5 subjects) free style.
      RESULTS: A general trend indicating a postexercise increase in spirometry was
      observed. We found post-exercise significant increments in FEV1 and in MEF75 for
      both the 800 and 1500 meter swimming sessions, and in FEF25-75 and in MEF25 for
      the shorter distance. CONCLUSIONS: We conclude that, as it may be expected,
      muscular exercise induces an improvement of spirometry both because of a smooth
      muscle relaxation-induced modulation of airway diameter and resistance to
      airflow, and because of an enhanced expiratory muscle contraction strength. Both
      of these mechanisms are related to an increased sympathetic activity which is
      well known to accompany muscular exercise.

PMID- 27882915
TI  - Characteristic of shoulder and hip rotation range of motion in adolescent tennis
      players.
AB  - BACKGROUND: Adolescent tennis players require sufficient hip and shoulder
      flexibility to achieve the kinetic chain of a tennis stroke or serve. Hence, the
      objective of this study is to measure the glenohumeral joint internal and
      external rotation (IR and ER, respectively) and hip ER range of motion (ROM) and
      to compare these parameters between experienced and beginner-level adolescent
      tennis players. METHODS: Twenty-three adolescent tennis players were divided into
      experienced (N.=12) and beginner groups (N.=11) on the basis of the adolescent
      national ranking of the Taiwan Tennis Association. For all participants, the
      shoulder IR and ER at 90 degrees  of abduction were measured, and hip ER which
      used Partick's Test was also evaluated on the dominant and nondominant sides. The
      total rotation ROM of the shoulder and the difference in shoulder ER, IR, and
      total rotation and hip ER between the dominant and nondominant sides were also
      calculated after measurements. An independent-samples t-test was applied to test
      the homogeneity of the participants' demographic data and the difference in
      shoulder IR, ER, and total rotation and hip ER values between the dominant and
      nondominant sides. Subsequently, a repeated-measured two-way analysis of variance
      (2 * 2) was used to compare the dominant and nondominant shoulder and hip ROM of
      the participants between the experienced and beginner groups. RESULTS: The
      experienced group exhibited a significantly less total rotation ROM than the
      beginner group. In addition, both groups showed less dominant shoulder IR ROM and
      more dominant shoulder ER ROM compared with the nondominant side. Compared with
      the experienced group, the beginner group showed an obvious difference in total
      shoulder rotation between dominant and nondominant sides. More tightness for the
      hip ER was observed in the experienced group than in the beginner group, but no
      difference was observed between the dominant and nondominant sides in both
      groups. CONCLUSIONS: Beginner adolescent tennis players differ more in the degree
      of total shoulder ROM between the dominant and nondominant sides than experienced
      players. Beginner and experienced adolescent tennis players also have more
      shoulder ER and less IR on the dominant side. The results suggest that beginner
      level adolescent tennis players should undergo a stretching and strengthening
      program to reduce the potential risk of injury and possibly enhance performance.

PMID- 27882917
TI  - Optically switched magnetism in photovoltaic perovskite CH3NH3(Mn:Pb)I3.
AB  - The demand for ever-increasing density of information storage and speed of
      manipulation boosts an intense search for new magnetic materials and novel ways
      of controlling the magnetic bit. Here, we report the synthesis of a ferromagnetic
      photovoltaic CH3NH3(Mn:Pb)I3 material in which the photo-excited electrons
      rapidly melt the local magnetic order through the Ruderman-Kittel-Kasuya-Yosida
      interactions without heating up the spin system. Our finding offers an
      alternative, very simple and efficient way of optical spin control, and opens an
      avenue for applications in low-power, light controlling magnetic devices.

PMID- 27882919
TI  - Interaction of the cotranslational Hsp70 Ssb with ribosomal proteins and rRNA
      depends on its lid domain.
AB  - Cotranslational chaperones assist in de novo folding of nascent polypeptides in
      all organisms. In yeast, the heterodimeric ribosome-associated complex (RAC)
      forms a unique chaperone triad with the Hsp70 homologue Ssb. We report the X-ray
      structure of full length Ssb in the ATP-bound open conformation at 2.6 A
      resolution and identify a positively charged region in the alpha-helical lid
      domain (SBDalpha), which is present in all members of the Ssb-subfamily of
      Hsp70s. Mutational analysis demonstrates that this region is strictly required
      for ribosome binding. Crosslinking shows that Ssb binds close to the tunnel exit
      via contacts with both, ribosomal proteins and rRNA, and that specific contacts
      can be correlated with switching between the open (ATP-bound) and closed (ADP
      bound) conformation. Taken together, our data reveal how Ssb dynamics on the
      ribosome allows for the efficient interaction with nascent chains upon RAC
      mediated activation of ATP hydrolysis.

PMID- 27882918
TI  - Hyperglycaemia induces metabolic dysfunction and glycogen accumulation in
      pancreatic beta-cells.
AB  - Insulin secretion from pancreatic beta-cells is impaired in all forms of
      diabetes. The resultant hyperglycaemia has deleterious effects on many tissues,
      including beta-cells. Here we show that chronic hyperglycaemia impairs glucose
      metabolism and alters expression of metabolic genes in pancreatic islets. In a
      mouse model of human neonatal diabetes, hyperglycaemia results in marked glycogen
      accumulation, and increased apoptosis in beta-cells. Sulphonylurea therapy
      rapidly normalizes blood glucose levels, dissipates glycogen stores, increases
      autophagy and restores beta-cell metabolism. Insulin therapy has the same effect
      but with slower kinetics. Similar changes are observed in mice expressing an
      activating glucokinase mutation, in in vitro models of hyperglycaemia, and in
      islets from type-2 diabetic patients. Altered beta-cell metabolism may underlie
      both the progressive impairment of insulin secretion and reduced beta-cell mass
      in diabetes.

PMID- 27882920
TI  - Repression of RNA polymerase by the archaeo-viral regulator ORF145/RIP.
AB  - Little is known about how archaeal viruses perturb the transcription machinery of
      their hosts. Here we provide the first example of an archaeo-viral transcription
      factor that directly targets the host RNA polymerase (RNAP) and efficiently
      represses its activity. ORF145 from the temperate Acidianus two-tailed virus
      (ATV) forms a high-affinity complex with RNAP by binding inside the DNA-binding
      channel where it locks the flexible RNAP clamp in one position. This counteracts
      the formation of transcription pre-initiation complexes in vitro and represses
      abortive and productive transcription initiation, as well as elongation. Both
      host and viral promoters are subjected to ORF145 repression. Thus, ORF145 has the
      properties of a global transcription repressor and its overexpression is toxic
      for Sulfolobus. On the basis of its properties, we have re-named ORF145 RNAP
      Inhibitory Protein (RIP).

PMID- 27882921
TI  - A mutation in VPS15 (PIK3R4) causes a ciliopathy and affects IFT20 release from
      the cis-Golgi.
AB  - Ciliopathies are a group of diseases that affect kidney and retina among other
      organs. Here, we identify a missense mutation in PIK3R4 (phosphoinositide 3
      kinase regulatory subunit 4, named VPS15) in a family with a ciliopathy
      phenotype. Besides being required for trafficking and autophagy, we show that
      VPS15 regulates primary cilium length in human fibroblasts, as well as ciliary
      processes in zebrafish. Furthermore, we demonstrate its interaction with the
      golgin GM130 and its localization to the Golgi. The VPS15-R998Q patient mutation
      impairs Golgi trafficking functions in humanized yeast cells. Moreover, in VPS15
      R998Q patient fibroblasts, the intraflagellar transport protein IFT20 is not
      localized to vesicles trafficking to the cilium but is restricted to the Golgi.
      Our findings suggest that at the Golgi, VPS15 and GM130 form a protein complex
      devoid of VPS34 to ensure the IFT20-dependent sorting and transport of membrane
      proteins from the cis-Golgi to the primary cilium.

PMID- 27882923
TI  - A DNA dual lock-and-key strategy for cell-subtype-specific siRNA delivery.
AB  - The efficient and precise delivery of siRNA to target cells is critical to
      successful gene therapy. While novel nanomaterials enhance delivery efficiency,
      it still remains challenging for precise gene delivery to overcome nonspecific
      adsorption and off-target effect. Here we design a dual lock-and-key system to
      perform cell-subtype-specific recognition and siRNA delivery. The siRNA is self
      assembled in an oligonucleotide nano vehicle that is modified with a hairpin
      structure to act as both the 'smart key' and the delivery carrier. The auto
      cleavable hairpin structure can be activated on site at target cell membrane by
      reacting with two aptamers as 'dual locks' sequentially, which leads to cell
      subtype discrimination and precise siRNA delivery for high efficient gene
      silencing. The success of this strategy demonstrates the precise delivery of
      siRNA to specific target cells by controlling multiple parameters, thus paving
      the way for application of RNAi in accurate diagnosis and intervention.

PMID- 27882922
TI  - An ethnically relevant consensus Korean reference genome is a step towards
      personal reference genomes.
AB  - Human genomes are routinely compared against a universal reference. However, this
      strategy could miss population-specific and personal genomic variations, which
      may be detected more efficiently using an ethnically relevant or personal
      reference. Here we report a hybrid assembly of a Korean reference genome (KOREF)
      for constructing personal and ethnic references by combining sequencing and
      mapping methods. We also build its consensus variome reference, providing
      information on millions of variants from 40 additional ethnically homogeneous
      genomes from the Korean Personal Genome Project. We find that the ethnically
      relevant consensus reference can be beneficial for efficient variant detection.
      Systematic comparison of human assemblies shows the importance of assembly
      quality, suggesting the necessity of new technologies to comprehensively map
      ethnic and personal genomic structure variations. In the era of large-scale
      population genome projects, the leveraging of ethnicity-specific genome
      assemblies as well as the human reference genome will accelerate mapping all
      human genome diversity.

PMID- 27882924
TI  - Deterministic phase slips in mesoscopic superconducting rings.
AB  - The properties of one-dimensional superconductors are strongly influenced by
      topological fluctuations of the order parameter, known as phase slips, which
      cause the decay of persistent current in superconducting rings and the appearance
      of resistance in superconducting wires. Despite extensive work, quantitative
      studies of phase slips have been limited by uncertainty regarding the order
      parameter's free-energy landscape. Here we show detailed agreement between
      measurements of the persistent current in isolated flux-biased rings and Ginzburg
      Landau theory over a wide range of temperature, magnetic field and ring size;
      this agreement provides a quantitative picture of the free-energy landscape. We
      also demonstrate that phase slips occur deterministically as the barrier
      separating two competing order parameter configurations vanishes. These results
      will enable studies of quantum and thermal phase slips in a well-characterized
      system and will provide access to outstanding questions regarding the nature of
      one-dimensional superconductivity.

PMID- 27882926
TI  - A CMOS silicon spin qubit.
AB  - Silicon, the main constituent of microprocessor chips, is emerging as a promising
      material for the realization of future quantum processors. Leveraging its well
      established complementary metal-oxide-semiconductor (CMOS) technology would be a
      clear asset to the development of scalable quantum computing architectures and to
      their co-integration with classical control hardware. Here we report a silicon
      quantum bit (qubit) device made with an industry-standard fabrication process.
      The device consists of a two-gate, p-type transistor with an undoped channel. At
      low temperature, the first gate defines a quantum dot encoding a hole spin qubit,
      the second one a quantum dot used for the qubit read-out. All electrical, two
      axis control of the spin qubit is achieved by applying a phase-tunable microwave
      modulation to the first gate. The demonstrated qubit functionality in a basic
      transistor-like device constitutes a promising step towards the elaboration of
      scalable spin qubit geometries in a readily exploitable CMOS platform.

PMID- 27882928
TI  - Electromagnon dispersion probed by inelastic X-ray scattering in LiCrO2.
AB  - Inelastic X-ray scattering with meV energy resolution (IXS) is an ideal tool to
      measure collective excitations in solids and liquids. In non-resonant scattering
      condition, the cross-section is strongly dominated by lattice vibrations
      (phonons). However, it is possible to probe additional degrees of freedom such as
      magnetic fluctuations that are strongly coupled to the phonons. The IXS spectrum
      of the coupled system contains not only the phonon dispersion but also the so far
      undetected magnetic correlation function. Here we report the observation of
      strong magnon-phonon coupling in LiCrO2 that enables the measurement of magnetic
      correlations throughout the Brillouin zone via IXS. We find electromagnon
      excitations and electric dipole active two-magnon excitations in the magnetically
      ordered phase and heavily damped electromagnons in the paramagnetic phase of
      LiCrO2. We predict that several (frustrated) magnets with dominant direct
      exchange and non-collinear magnetism show surprisingly large IXS cross-section
      for magnons and multi-magnon processes.

PMID- 27882925
TI  - ISGylation controls exosome secretion by promoting lysosomal degradation of MVB
      proteins.
AB  - Exosomes are vesicles secreted to the extracellular environment through fusion
      with the plasma membrane of specific endosomes called multivesicular bodies (MVB)
      and mediate cell-to-cell communication in many biological processes.
      Posttranslational modifications are involved in the sorting of specific proteins
      into exosomes. Here we identify ISGylation as a ubiquitin-like modification that
      controls exosome release. ISGylation induction decreases MVB numbers and impairs
      exosome secretion. Using ISG15-knockout mice and mice expressing the
      enzymatically inactive form of the de-ISGylase USP18, we demonstrate in vitro and
      in vivo that ISG15 conjugation regulates exosome secretion. ISG15 conjugation
      triggers MVB co-localization with lysosomes and promotes the aggregation and
      degradation of MVB proteins. Accordingly, inhibition of lysosomal function or
      autophagy restores exosome secretion. Specifically, ISGylation of the MVB protein
      TSG101 induces its aggregation and degradation, being sufficient to impair
      exosome secretion. These results identify ISGylation as a novel ubiquitin-like
      modifier in the control of exosome production.

PMID- 27882927
TI  - Global gain modulation generates time-dependent urgency during perceptual choice
      in humans.
AB  - Decision-makers must often balance the desire to accumulate information with the
      costs of protracted deliberation. Optimal, reward-maximizing decision-making can
      require dynamic adjustment of this speed/accuracy trade-off over the course of a
      single decision. However, it is unclear whether humans are capable of such time
      dependent adjustments. Here, we identify several signatures of time-dependency in
      human perceptual decision-making and highlight their possible neural source.
      Behavioural and model-based analyses reveal that subjects respond to deadline
      induced speed pressure by lowering their criterion on accumulated perceptual
      evidence as the deadline approaches. In the brain, this effect is reflected in
      evidence-independent urgency that pushes decision-related motor preparation
      signals closer to a fixed threshold. Moreover, we show that global modulation of
      neural gain, as indexed by task-related fluctuations in pupil diameter, is a
      plausible biophysical mechanism for the generation of this urgency. These
      findings establish context-sensitive time-dependency as a critical feature of
      human decision-making.

PMID- 27882930
TI  - Hypertension is an important risk determinant for chronic kidney disease: results
      from a cross-sectional, observational study from a rural population in South
      India.
AB  - Hypertension (HTN) is an important cause for chronic kidney disease (CKD). There
      is a paucity of studies exploring the association of HTN with CKD from rural
      India. The objective of the study was to determine the prevalence and the
      determinants for HTN in a rural population in South India, focusing on the
      association with CKD. In a cross-sectional study on 2984 adults in three
      villages, demographic and anthropometric data were collected. Blood pressure was
      recorded on all individuals and prevalence was estimated. Proteinuria,
      microalbuminuria (MA) and estimated glomerular filtration rate (eGFR) were
      determined in a subgroup of 1331 subjects and the relation with HTN was analysed.
      Prevalence of HTN was 30.4% (95% CI 28.75-32.05%). In all, 78.08% had stage 1 HTN
      while 22% had stage 2 HTN. In total, 27.4% (249/908) subjects were aware of their
      hypertensive status. Of them, only 14.4% had adequate control of blood pressure.
      Age>50 years, diabetes, body mass index >25 and eGFR<60 ml min-1 were independent
      significant predictors of HTN (P<0.05). HTN was found to be an important risk
      factor for CKD even after adjusting for age, diabetes and cardiovascular risk
      factors (OR 2.22, 95% CI 1.46-3.36, P<0.001). The high prevalence of HTN, very
      low level of awareness and control, and the significant association with kidney
      disease indicate a need for stronger public health initiative with better
      penetration for awareness and screening for HTN and CKD in India's villages.

PMID- 27882931
TI  - Plasma Sfrp5 and adiponectin levels in relation to blood pressure among obese
      children.
AB  - The aim was to clarify the associations of five adipocytokines: Sfrp5, Wnt5a,
      adiponectin, chemerin and high-sensitivity C-reactive protein (hsCRP) with blood
      pressure (BP), and to examine whether BP can be influenced by changes in these
      adipocytokines in obese children after a 6-month lifestyle intervention. We
      conducted a cross-sectional study in 263 obese children and performed a 6-month
      lifestyle intervention in a subgroup of 89 obese children with hypertension.
      Anthropometric data, adiponectin, chemerin, Sfrp5 and Wnt5a were assessed at
      baseline and after 6-month lifestyle intervention. Sfrp5 and adiponectin serum
      levels were significantly lower in obese children with hypertension, but Wnt5a,
      hsCRP and chemerin serum levels were elevated in obese children with
      hypertension. In multivariable linear regression analysis, Sfrp5, Wnt5a,
      adiponectin, chemerin and hsCRP were associated with both standard deviation
      score-systolic blood pressure (SDS-SBP) and -diastolic blood pressure (SDS-DBP).
      Lifestyle intervention resulted in a significant improvement in BP and weight
      loss. These were accompanied by significant decreases in hsCRP and chemerin, and
      significant increases in Sfrp5 and adiponectin, whereas Wnt5a was not changed.
      Furthermore, the changes in Sfrp5 and adiponectin act as partial mediators of the
      relationship between weight loss and BP reduction after controlling for
      covariates. Although Sfrp5, Wnt5a, adiponectin, chemerin and hsCRP levels are
      correlated with BP at baseline, after lifestyle intervention, the relationship
      between weight loss and BP reduction were partially mediated by changes in Sfrp5
      and adiponectin after controlling for covariates. So we speculate that Sfrp5 and
      adiponectin may have some influence on BP.

PMID- 27882929
TI  - Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by
      modifying the tumour microenvironment.
AB  - Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory
      tumour microenvironment and the progression of colorectal cancer (CRC). We report
      here that the expression level of sST2, a soluble form of the IL-33 receptor
      (ST2L), is inversely associated with the malignant growth of CRC. sST2 is
      downregulated in high-metastatic cells compared with low-metastatic human and
      mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumour
      growth, metastasis and tumour angiogenesis, whereas its overexpression in high
      metastatic cells suppresses these processes. Circulating and intratumourally
      administered sST2-Fc fusion protein reduce tumour growth, metastatic spread and
      tumour angiogenesis in mice bearing high-metastatic CRC. Mechanistically, sST2
      suppresses IL-33-induced angiogenesis, Th1- and Th2-responses, macrophage
      infiltration and macrophage M2a polarization. In conclusion, we show that sST2
      negatively regulates tumour growth and the metastatic spread of CRC through
      modification of the tumour microenvironment. Thus, the IL-33/ST2L axis may be a
      potential therapeutic target in CRC.

PMID- 27882932
TI  - Tunable inertia of chiral magnetic domain walls.
AB  - The time it takes to accelerate an object from zero to a given velocity depends
      on the applied force and the environment. If the force ceases, it takes exactly
      the same time to completely decelerate. A magnetic domain wall is a topological
      object that has been observed to follow this behaviour. Here we show that
      acceleration and deceleration times of chiral Neel walls driven by current are
      different in a system with low damping and moderate Dzyaloshinskii-Moriya
      exchange constant. The time needed to accelerate a domain wall with current via
      the spin Hall torque is much faster than the time it needs to decelerate once the
      current is turned off. The deceleration time is defined by the Dzyaloshinskii
      Moriya exchange constant whereas the acceleration time depends on the spin Hall
      torque, enabling tunable inertia of chiral domain walls. Such unique feature of
      chiral domain walls can be utilized to move and position domain walls with lower
      current, key to the development of storage class memory devices.

PMID- 27882933
TI  - Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and
      interferes with CDCA7L expression.
AB  - Genome-wide association studies have identified several risk loci for multiple
      myeloma (MM); however, the mechanisms by which they influence MM are unknown.
      Here by using genetic association data and functional characterization, we
      demonstrate that rs4487645 G>T, the most highly associated variant (P = 5.30 * 10
      25), resides in an enhancer element 47 kb upstream of the transcription start
      site of c-Myc-interacting CDCA7L. The G-risk allele, associated with increased
      CDCA7L expression (P=1.95 * 10-36), increases IRF4 binding and the enhancer
      interacts with the CDCA7L promoter. We show that suppression of CDCA7L limits MM
      proliferation through apoptosis, and increased CDCA7L expression is associated
      with adverse patient survival. These findings implicate IRF4-mediated CDCA7L
      expression in MM biology and indicate how germline variation might confer
      susceptibility to MM.

PMID- 27882934
TI  - Macrophage-dependent IL-1beta production induces cardiac arrhythmias in diabetic
      mice.
AB  - Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including
      heart disease. One of the most frequent and potentially life threatening
      disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we
      show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in
      cardiac macrophages mediate the production of IL-1beta in DM mice. IL-1beta
      causes prolongation of the action potential duration, induces a decrease in
      potassium current and an increase in calcium sparks in cardiomyocytes, which are
      changes that underlie arrhythmia propensity. IL-1beta-induced spontaneous
      contractile events are associated with CaMKII oxidation and phosphorylation. We
      further show that DM-induced arrhythmias can be successfully treated by
      inhibiting the IL-1beta axis with either IL-1 receptor antagonist or by
      inhibiting the NLRP3 inflammasome. Our results establish IL-1beta as an
      inflammatory connection between metabolic dysfunction and arrhythmias in DM.

PMID- 27882935
TI  - The Robo4 cytoplasmic domain is dispensable for vascular permeability and
      neovascularization.
AB  - Vascular permeability and neovascularization are implicated in many diseases
      including retinopathies and diabetic wound healing. Robo4 is an endothelial
      specific transmembrane receptor that stabilizes the vasculature, as shown in
      Robo4-/- mice that develop hyperpermeability, but how Robo4 signals remained
      unclear. Here we show that Robo4 deletion enhances permeability and
      revascularization in oxygen-induced retinopathy (OIR) and accelerates cutaneous
      wound healing. To determine Robo4 signalling pathways, we generated transgenic
      mice expressing a truncated Robo4 lacking the cytoplasmic domain (Robo4DeltaCD).
      Robo4DeltaCD expression is sufficient to prevent permeability, and inhibits OIR
      revascularization and wound healing in Robo4-/- mice. Mechanistically, Robo4 does
      not affect Slit2 signalling, but Robo4 and Robo4DeltaCD counteract Vegfr2-Y949
      (Y951 in human VEGFR2) phosphorylation by signalling through the endothelial
      UNC5B receptor. We conclude that Robo4 inhibits angiogenesis and vessel
      permeability independently of its cytoplasmic domain, while activating VEGFR2
      Y951 via ROBO4 inhibition might accelerate tissue revascularization in
      retinopathy of prematurity and in diabetic patients.

PMID- 27882936
TI  - The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with
      distinct activities.
AB  - According to dogma, initiator caspases are activated through proximity-induced
      homodimerization, but some studies infer that during apoptosis caspase-9 may
      instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical
      approaches, including a novel site-specific crosslinking technique, we provide
      the first direct evidence that procaspase-9 homodimerizes within the apoptosome,
      markedly increasing its avidity for the complex and inducing selective
      intramolecular cleavage at Asp-315. Remarkably, however, procaspase-9 could also
      bind via its small subunit to the NOD domain in Apaf-1, resulting in the
      formation of a heterodimer that more efficiently activated procaspase-3.
      Following cleavage, the intersubunit linker (and associated conformational
      changes) in caspase-9-p35/p12 inhibited its ability to form homo- and
      heterodimers, but feedback cleavage by caspase-3 at Asp-330 removed the linker
      entirely and partially restored activity to caspase-9-p35/p10. Thus, the
      apoptosome mediates the formation of caspase-9 homo- and heterodimers, both of
      which are impacted by cleavage and contribute to its overall function.

PMID- 27882937
TI  - EZH2 mediates lidamycin-induced cellular senescence through regulating p21
      expression in human colon cancer cells.
AB  - Lidamycin (LDM) is a novel member of the enediyne antibiotics identified in China
      with potent antitumor activity. However, it remains unclear whether LDM has
      potential molecular targets that may affect its antitumor activity. Enhancer of
      zeste homolog 2 (EZH2) functions as a histone lysine methyltransferase and
      mediates trimethylation on histone 3 lysine 27 (H3K27me3). High EZH2 level is
      found to be positively correlated with the aggressiveness, metastasis and poor
      prognosis of cancer. Here, we aim to study the role of EZH2 in LDM-induced
      senescence, as well as in the cytotoxicity of LDM in human colon cancer cells.
      LDM is found to be relatively more potent in inhibiting the colon cancer cells
      harboring high EZH2 level and induces irreversible cellular senescence at IC50
      dose range, as evidenced by senescence-associated beta-galactosidase staining,
      cell cycle arrest and molecular changes of senescence regulators including p21 in
      HCT116 and SW620 cells. More importantly, LDM is found to markedly inhibit EZH2
      expression at both protein and mRNA levels upon the induction of p21 and cellular
      senescence. LDM also selectively inhibits EZH2 expression as compared with other
      histone lysine methyltransferases. Knockdown of p21 with siRNAs abolishes LDM
      induced senescence, whereas EZH2 knockdown markedly increases p21 expression and
      causes senescent phenotype. Enrichment of both EZH2 and H3K27me3 levels in the
      p21 promoter region is reduced by LDM. Moreover, EZH2 overexpression reduces
      cellular senescence, p21 expression and DNA damage response upon LDM exposure.
      LDM also demonstrates potent antitumor efficacy in xenografted animal models.
      Collectively, our work provides first demonstration that EZH2 may mediate, at
      least partially, the senescence-inducing effects of LDM by regulating p21
      expression and DNA damage effect. Thus, EZH2 may serve as a potential target and
      biomarker to indicate the clinical efficacy of the potent enediyne antitumor
      drug.

PMID- 27882938
TI  - Neutral sphingomyelinase (SMPD3) deficiency disrupts the Golgi secretory pathway
      and causes growth inhibition.
AB  - Systemic loss of neutral sphingomyelinase (SMPD3) in mice leads to a novel form
      of systemic, juvenile hypoplasia (dwarfism). SMPD3 deficiency in mainly two
      growth regulating cell types contributes to the phenotype, in chondrocytes of
      skeletal growth zones to skeletal malformation and chondrodysplasia, and in
      hypothalamic neurosecretory neurons to systemic hypothalamus-pituitary
      somatotropic hypoplasia. The unbiased smpd3-/- mouse mutant and derived smpd3-/-
      primary chondrocytes were instrumental in defining the enigmatic role underlying
      the systemic and cell autonomous role of SMPD3 in the Golgi compartment. Here we
      describe the unprecedented role of SMPD3. SMPD3 deficiency disrupts homeostasis
      of sphingomyelin (SM), ceramide (Cer) and diacylglycerol (DAG) in the Golgi SMPD3
      SMS1 (SM-synthase1) cycle. Cer and DAG, two fusogenic intermediates, modify the
      membrane lipid bilayer for the initiation of vesicle formation and transport.
      Dysproteostasis, unfolded protein response, endoplasmic reticulum stress and
      apoptosis perturb the Golgi secretory pathway in the smpd3-/- mouse. Secretion of
      extracellular matrix proteins is arrested in chondrocytes and causes skeletal
      malformation and chondrodysplasia. Similarly, retarded secretion of proteo
      hormones in hypothalamic neurosecretory neurons leads to hypothalamus induced
      combined pituitary hormone deficiency. SMPD3 in the regulation of the protein
      vesicular secretory pathway may become a diagnostic target in the etiology of
      unknown forms of juvenile growth and developmental inhibition.

PMID- 27882939
TI  - Direct regulation of FOXK1 by C-jun promotes proliferation, invasion and
      metastasis in gastric cancer cells.
AB  - Forkhead box (FOX) K1 is a member of the FOX transcription factor superfamily.
      High FOXK1 expression is associated with several cancers. However, whether FOXK1
      expression contributes to gastric cancer (GC) development and progression remains
      unknown. We analyzed the FOXK1 promoter using the Promo software and found
      several binding sequence transcription factors, including c-jun. However, the
      molecular mechanism by which FOXK1 affects the c-jun-mediated malignant phenotype
      is poorly understood. Here, we found that FOXK1 protein expression was higher in
      8/10 (80.0%) fresh cancer tissues compared with that in adjacent normal tissues.
      FOXK1 overexpression enhanced the proliferation, migration and invasion of GC
      cells. Moreover, FOXK1 expression was stimulated by transforming growth factor
      beta1 (TGF-beta1). FOXK1 acted as a potential epithelial-to-mesenchymal
      transition (EMT) inducer by stimulating vimentin expression and inducing the loss
      of E-cadherin in stable FOXK1-transfected cells. The results of promoter reporter
      and chromatin immunoprecipitation assays demonstrated that c-jun directly binds
      to and activates the human FOXK1 gene promoter. A positive correlation was
      observed between the expression patterns of FOXK1 and c-jun in GC cells and
      tissue. FOXK1 and c-jun expression were correlated with tumor progression and
      represented significant predictors of overall survival in GC patients. However,
      the siRNA-mediated repression of c-jun in FOXK1-overexpressing cells reversed
      EMT, as well as the proliferative and metastatic phenotypes. In vivo, c-jun
      promoted FOXK1-mediated proliferation and metastasis via orthotopic implantation.
      The evidence presented here suggests that FOXK1-directed regulation by c-jun
      promote the development and progression of human GC.

PMID- 27882941
TI  - TGF-beta signaling controls FSHR signaling-reduced ovarian granulosa cell
      apoptosis through the SMAD4/miR-143 axis.
AB  - Follicle-stimulating hormone receptor (FSHR) and its intracellular signaling
      control mammalian follicular development and female infertility. Our previous
      study showed that FSHR is downregulated during follicular atresia of porcine
      ovaries. However, its role and regulation in follicular atresia remain unclear.
      Here, we showed that FSHR knockdown induced porcine granulosa cell (pGC)
      apoptosis and follicular atresia, and attenuated the levels of intracellular
      signaling molecules such as PKA, AKT and p-AKT. FSHR was identified as a target
      of miR-143, a microRNA that was upregulated during porcine follicular atresia.
      miR-143 enhanced pGC apoptosis by targeting FSHR, and reduced the levels of
      intracellular signaling molecules. SMAD4, the final molecule in transforming
      growth factor (TGF)-beta signaling, bound to the promoter and induced significant
      downregulation of miR-143 in vitro and in vivo. Activated TGF-beta signaling
      rescued miR-143-reduced FSHR and intracellular signaling molecules, and miR-143
      induced pGC apoptosis. Overall, our findings offer evidence to explain how TGF
      beta signaling influences and FSHR signaling for regulation of pGC apoptosis and
      follicular atresia by a specific microRNA, miR-143.

PMID- 27882940
TI  - MDM2 prevents spontaneous tubular epithelial cell death and acute kidney injury.
AB  - Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative
      regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as
      a modulator of NF-kB signaling. As such it promotes proliferation and
      inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial
      cells and we hypothesized that MDM2 is necessary for their survival and
      homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise
      of tubular cells in vitro. This phenotype was completely rescued by concomitant
      knockdown of p53, thus suggesting p53 dependency. In vivo experiments in the
      zebrafish model demonstrated that the tubulus cells of the larvae undergo cell
      death after the knockdown of mdm2. Doxycycline-induced deletion of MDM2 in
      tubular cell-specific MDM2-knockout mice Pax8rtTa-cre; MDM2f/f caused acute
      kidney injury with increased plasma creatinine and blood urea nitrogen and sharp
      decline of glomerular filtration rate. Histological analysis showed massive
      swelling of renal tubular cells and later their loss and extensive tubular
      dilation, markedly in proximal tubules. Ultrastructural changes of tubular
      epithelial cells included swelling of the cytoplasm and mitochondria with the
      loss of cristae and their transformation in the vacuoles. The pathological
      phenotype of the tubular cell-specific MDM2-knockout mouse model was completely
      rescued by co-deletion of p53. Tubular epithelium compensates only partially for
      the cell loss caused by MDM2 depletion by proliferation of surviving tubular
      cells, with incomplete MDM2 deletion, but rather mesenchymal healing occurs. We
      conclude that MDM2 is a non-redundant survival factor for proximal tubular cells
      by protecting them from spontaneous p53 overexpression-related cell death.

PMID- 27882943
TI  - Metadherin facilitates podocyte apoptosis in diabetic nephropathy.
AB  - Apoptosis, one of the major causes of podocyte loss, has been reported to have a
      vital role in diabetic nephropathy (DN) pathogenesis, and understanding the
      mechanisms underlying the regulation of podocyte apoptosis is crucial. Metadherin
      (MTDH) is an important oncogene, which is overexpressed in most cancers and
      responsible for apoptosis, metastasis, and poor patient survival. Here we show
      that the expression levels of Mtdh and phosphorylated p38 mitogen-activated
      protein kinase (MAPK) are significantly increased, whereas those of the microRNA
      30 family members (miR-30s) are considerably reduced in the glomeruli of DN rat
      model and in high glucose (HG)-induced conditionally immortalized mouse podocytes
      (MPC5). These levels are positively correlated with podocyte apoptosis rate. The
      inhibition of Mtdh expression, using small interfering RNA, but not Mtdh
      overexpression, was shown to inhibit HG-induced MPC5 apoptosis and p38 MAPK
      pathway, and Bax and cleaved caspase 3 expression. This was shown to be similar
      to the effects of p38 MAPK inhibitor (SB203580). Furthermore, luciferase assay
      results demonstrated that Mtdh represents the target of miR-30s. Transient
      transfection experiments, using miR-30 microRNA (miRNA) inhibitors, led to the
      increase in Mtdh expression and induced the apoptosis of MPC5, whereas the
      treatment with miR-30 miRNA mimics led to the reduction in Mtdh expression and
      apoptosis of HG-induced MPC5 cells in comparison with their respective controls.
      Our results demonstrate that Mtdh is a potent modulator of podocyte apoptosis,
      and that it represents the target of miR-30 miRNAs, facilitating podocyte
      apoptosis through the activation of HG-induced p38 MAPK-dependent pathway.

PMID- 27882942
TI  - Emerging roles of extracellular vesicles in neurodegenerative disorders: focus on
      HIV-associated neurological complications.
AB  - Exosomes are membrane-enriched extracellular vesicles with a proposed diameter in
      the range of 30-100 nm. They are released during both normal homeostasis as well
      as under pathological conditions by most cell types. In recent years, there has
      been robust interest in the study of these vesicles as conduits for the delivery
      of information between cells in both analogous as well as disparate tissues.
      Their ability to transport specialized cargo including signaling mediators,
      proteins, messenger RNA and miRNAs characterizes these vesicles as primary
      facilitators of cell-to-cell communication and regulation. Exosomes have also
      been demonstrated to have important roles in the field of cancer biology and
      metastasis. More recently, their role in several neurodegenerative disorders has
      been gaining increased momentum as these particles have been shown to promote the
      spread of toxic factors such as amyloid beta and prions, adding further validity
      to their role as important regulators of disease pathogenesis. This review
      briefly summarizes current findings and thoughts on exosome biology in the
      context of neurodegenerative disorders and the manipulation of these particles
      for the development of potential therapeutic strategies.

PMID- 27882944
TI  - GRK6 regulates ROS response and maintains hematopoietic stem cell self-renewal.
AB  - G protein-coupled receptor kinases (GRKs) are critically involved in immune
      response through regulation of cytokine receptors in mature leukocytes, but their
      role in hematopoiesis is largely unknown. Here, we demonstrate that GRK6 knockout
      (GRK6-/-) mice exhibit lymphocytopenia, loss of the hematopoietic stem cell (HSC)
      and multiple progenitor populations. GRK6 deficiency leads to compromised
      lymphoid differentiation, largely owing to the impairment of HSC self-renewal.
      Transcriptome and proteomic analysis suggest that GRK6 is involved in reactive
      oxygen species signaling. GRK6 could interact with DNA-PKcs (DNA-dependent
      protein kinase, catalytic subunit) and regulate its phosphorylation. Moreover,
      reactive oxygen species scavenger alpha-lipoic acid administration could
      partially rescue the loss of HSC in GRK6-/- mice. Our work demonstrates the
      importance of GRK6 in regulation of HSC self-renewal and reveals its potential
      role in participation of stress response.

PMID- 27882945
TI  - Adiponectin reduces ER stress-induced apoptosis through PPARalpha transcriptional
      regulation of ATF2 in mouse adipose.
AB  - Adiponectin is a cytokine produced predominantly by adipose tissue and correlates
      with glucose and lipid homeostasis. However, the effects of adiponectin on
      endoplasmic reticulum (ER) stress and apoptosis of adipose tissue remain elusive.
      In this study, we found that tunicamycin-induced ER stress increased serum free
      fatty acid (FFA) and impaired glucose tolerance, elevated the mRNA levels of
      GRP78, Chop, ATF2 and caspase 3, but reduced adiponectin mRNA level in white
      adipose tissue. Moreover, ER stress-triggered adipocyte apoptosis by increasing
      cellular FFA level and Ca2+ level. Further analysis revealed that adiponectin
      alleviated ER stress-induced adipocyte apoptosis by elevating peroxisome
      proliferator-activated receptor alpha (PPARalpha) mRNA level. Our data also
      confirmed that adiponectin reduced early apoptotic cells and blocked the
      mitochondrial apoptosis pathway by activating the AdipoR1/AMP-activated protein
      kinase (AMPK) signal pathway. In addition, PPARalpha bound to ATF2 promoter
      region and inhibited transcription of ATF2. The inhibition of adipocyte apoptosis
      by adiponectin was correlated with transcriptional suppression of ATF2.
      Furthermore, adiponectin inhibited ER stress-induced apoptosis by activating the
      AMPK/PKC pathway. In summary, our data demonstrate adiponectin inhibited ER
      stress and apoptosis of adipocyte in vivo and in vitro by activating the
      AMPK/PPARalpha/ATF2 pathway. Our study establishes that adiponectin is an
      important adipocytokine for preventing and treating obesity.

PMID- 27882946
TI  - ER stress inhibitor attenuates hearing loss and hair cell death in Cdh23erl/erl
      mutant mice.
AB  - Hearing loss is one of the most common sensory impairments in humans. Mouse
      mutant models helped us to better understand the mechanisms of hearing loss.
      Recently, we have discovered that the erlong (erl) mutation of the cadherin23
      (Cdh23) gene leads to hearing loss due to hair cell apoptosis. In this study, we
      aimed to reveal the molecular pathways upstream to apoptosis in hair cells to
      exploit more effective therapeutics than an anti-apoptosis strategy. Our results
      suggest that endoplasmic reticulum (ER) stress is the earliest molecular event
      leading to the apoptosis of hair cells and hearing loss in erl mice. We also
      report that the ER stress inhibitor, Salubrinal (Sal), could delay the
      progression of hearing loss and preserve hair cells. Our results provide evidence
      that therapies targeting signaling pathways in ER stress development prevent hair
      cell apoptosis at an early stage and lead to better outcomes than those targeting
      downstream factors, such as tip-link degeneration and apoptosis.

PMID- 27882947
TI  - Arginase 2 promotes neurovascular degeneration during ischemia/reperfusion
      injury.
AB  - Retinal ischemia is a major cause of visual impairment and blindness and is
      involved in various disorders including diabetic retinopathy, glaucoma, optic
      neuropathies and retinopathy of prematurity. Neurovascular degeneration is a
      common feature of these pathologies. Our lab has previously reported that the
      ureahydrolase arginase 2 (A2) is involved in ischemic retinopathies. Here, we are
      introducing A2 as a therapeutic target to prevent neurovascular injury after
      retinal ischemia/reperfusion (I/R) insult. Studies were performed with mice
      lacking both copies of A2 (A2-/-) and wild-type (WT) controls (C57BL6J). I/R
      insult was conducted on the right eye and the left eye was used as control.
      Retinas were collected for analysis at different times (3 h-4 week after injury).
      Neuronal and microvascular degeneration were evaluated using NeuN staining and
      vascular digests, respectively. Glial activation was evaluated by glial
      fibrillary acidic protein expression. Necrotic cell death was studied by
      propidium iodide labeling and western blot for RIP-3. Arginase expression was
      determined by western blot and quantitative RT-PCR. Retinal function was
      determined by electroretinography (ERG). A2 mRNA and protein levels were
      increased in WT I/R. A2 deletion significantly reduced ganglion cell loss and
      microvascular degeneration and preserved retinal morphology after I/R. Glial
      activation, reactive oxygen species formation and cell death by necroptosis were
      significantly reduced by A2 deletion. ERG showed improved positive scotopic
      threshold response with A2 deletion. This study shows for the first time that
      neurovascular injury after retinal I/R is mediated through increased expression
      of A2. Deletion of A2 was found to be beneficial in reducing neurovascular
      degeneration after I/R.

PMID- 27882949
TI  - SUMO-specific protease 1 protects neurons from apoptotic death during transient
      brain ischemia/reperfusion.
AB  - SUMO-specific protease 1 (SENP1) deconjugates SUMO from modified proteins.
      Although post-ischemic activation of SUMO conjugation was suggested to be
      neuroprotective against ischemia/reperfusion (I/R) injury, the function of SENP1
      in this process remained unclear. Here we show that transient middle cerebral
      artery occlusion in mice followed by 6, 12 and 24 h reperfusion significantly
      enhanced SENP1 levels in the affected brain area, independent of transcription.
      Consistent with the increase in SENP1, the levels of SUMO1-conjugated proteins
      were decreased by I/R in cortical neurons of control littermate mice, but
      unchanged in that of animals with conditional ablation of SENP1 gene from adult
      principal neurons, the SENP1flox/flox:CamKIIalpha-Cre (SENP1 cKO) mice. The SENP1
      cKO mice exhibited a significant increase in infarct volume in the cerebral
      cortex and more severe motor impairment in response to I/R as compared with the
      control littermates. Cortical neurons from I/R-injured SENP1 cKO mice became more
      apoptotic than that from control littermates, as indicated by both TUNEL staining
      and caspase-3 activation. Overexpression of SENP1 in somatosensory cortices of
      adult wild-type (WT) mice suppressed I/R-induced neuronal apoptosis. We conclude
      that SENP1 plays a neuroprotective role in I/R injury by inhibiting apoptosis
      through decreasing SUMO1 conjugation. These findings reveal a novel mechanism of
      neuroprotection by protein desumoylation, which may help develop new therapies
      for mitigating brain injury associated with ischemic stroke.

PMID- 27882952
TI  - Biochemistry: A fast way to convert carbon.

PMID- 27882948
TI  - The non-canonical Wnt receptor Ryk regulates hematopoietic stem cell repopulation
      in part by controlling proliferation and apoptosis.
AB  - The development of blood and immune cells requires strict control by various
      signaling pathways in order to regulate self-renewal, differentiation and
      apoptosis in stem and progenitor cells. Recent evidence indicates critical roles
      for the canonical and non-canonical Wnt pathways in hematopoiesis. The non
      canonical Wnt pathway is important for establishment of cell polarity and cell
      migration and regulates apoptosis in the thymus. We here investigate the role of
      the non-canonical Wnt receptor Ryk in hematopoiesis and lymphoid development. We
      show that there are dynamic changes in Ryk expression during development and in
      different hematopoietic tissues. Functionally, Ryk regulates NK cell development
      in a temporal fashion. Moreover, Ryk-deficient mice show diminished, but not
      absent self-renewal of hematopoietic stem cells (HSC), via effects on mildly
      increased proliferation and apoptosis. Thus, Ryk deficiency in HSCs from fetal
      liver reduces their quiescence, leading to proliferation-induced apoptosis and
      decreased self-renewal.

PMID- 27882953
TI  - Genomics: DNA reveals history of maize.

PMID- 27882951
TI  - Trump: keep climate plans to boost jobs.

PMID- 27882950
TI  - Neutralization mechanism of a highly potent antibody against Zika virus.
AB  - The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain
      Barre syndrome, signals an urgency to identify therapeutics. Recent efforts to
      rescreen dengue virus human antibodies for ZIKV cross-neutralization activity
      showed antibody C10 as one of the most potent. To investigate the ability of the
      antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV
      complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late
      endosomal (pH5.0) environments. The 4.0 A resolution pH8.0 complex structure
      shows that the antibody binds to E proteins residues at the intra-dimer
      interface, and the virus quaternary structure-dependent inter-dimer and inter
      raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and
      at pH5.0, it locks the E protein raft structure, suggesting that it prevents the
      structural rearrangement of the E proteins during the fusion event-a vital step
      for infection. This suggests antibody C10 could be a good therapeutic candidate.

PMID- 27882955
TI  - Plant biology: Rapid recovery boosts plant yields.

PMID- 27882956
TI  - Trump: unlikely to deter clean energy.

PMID- 27882958
TI  - Ecology: Ants farm plants in Fiji.

PMID- 27882959
TI  - Materials science: Polymers make charge flow easy.

PMID- 27882957
TI  - Mirazon Lahr et al. reply.

PMID- 27882960
TI  - Astrophysics: Homing in on a fast radio burst.

PMID- 27882961
TI  - Trump: China could take lead on climate.

PMID- 27882965
TI  - Biochemistry: Catalyst clicks drugs together.

PMID- 27882966
TI  - Plant science: A war over water when bacteria invade leaves.

PMID- 27882964
TI  - Bacteria establish an aqueous living space in plants crucial for virulence.
AB  - High humidity has a strong influence on the development of numerous diseases
      affecting the above-ground parts of plants (the phyllosphere) in crop fields and
      natural ecosystems, but the molecular basis of this humidity effect is not
      understood. Previous studies have emphasized immune suppression as a key step in
      bacterial pathogenesis. Here we show that humidity-dependent, pathogen-driven
      establishment of an aqueous intercellular space (apoplast) is another important
      step in bacterial infection of the phyllosphere. Bacterial effectors, such as
      Pseudomonas syringae HopM1, induce establishment of the aqueous apoplast and are
      sufficient to transform non-pathogenic P. syringae strains into virulent
      pathogens in immunodeficient Arabidopsis thaliana under high humidity.
      Arabidopsis quadruple mutants simultaneously defective in a host target (AtMIN7)
      of HopM1 and in pattern-triggered immunity could not only be used to reconstitute
      the basic features of bacterial infection, but also exhibited humidity-dependent
      dyshomeostasis of the endophytic commensal bacterial community in the
      phyllosphere. These results highlight a new conceptual framework for
      understanding diverse phyllosphere-bacterial interactions.

PMID- 27882968
TI  - Population genetics: Clues to shy sharks in seawater DNA.

PMID- 27882971
TI  - Genomics: Epidemics marked indigenous DNA.

PMID- 27882967
TI  - Senturk et al. reply.

PMID- 27882973
TI  - The evolving quality of frictional contact with graphene.
AB  - Graphite and other lamellar materials are used as dry lubricants for macroscale
      metallic sliding components and high-pressure contacts. It has been shown
      experimentally that monolayer graphene exhibits higher friction than multilayer
      graphene and graphite, and that this friction increases with continued sliding,
      but the mechanism behind this remains subject to debate. It has long been
      conjectured that the true contact area between two rough bodies controls
      interfacial friction. The true contact area, defined for example by the number of
      atoms within the range of interatomic forces, is difficult to visualize directly
      but characterizes the quantity of contact. However, there is emerging evidence
      that, for a given pair of materials, the quality of the contact can change, and
      that this can also strongly affect interfacial friction. Recently, it has been
      found that the frictional behaviour of two-dimensional materials exhibits traits
      unlike those of conventional bulk materials. This includes the abovementioned
      finding that for few-layer two-dimensional materials the static friction force
      gradually strengthens for a few initial atomic periods before reaching a constant
      value. Such transient behaviour, and the associated enhancement of steady-state
      friction, diminishes as the number of two-dimensional layers increases, and was
      observed only when the two-dimensional material was loosely adhering to a
      substrate. This layer-dependent transient phenomenon has not been captured by any
      simulations. Here, using atomistic simulations, we reproduce the experimental
      observations of layer-dependent friction and transient frictional strengthening
      on graphene. Atomic force analysis reveals that the evolution of static friction
      is a manifestation of the natural tendency for thinner and less-constrained
      graphene to re-adjust its configuration as a direct consequence of its greater
      flexibility. That is, the tip atoms become more strongly pinned, and show greater
      synchrony in their stick-slip behaviour. While the quantity of atomic-scale
      contacts (true contact area) evolves, the quality (in this case, the local
      pinning state of individual atoms and the overall commensurability) also evolves
      in frictional sliding on graphene. Moreover, the effects can be tuned by pre
      wrinkling. The evolving contact quality is critical for explaining the time
      dependent friction of configurationally flexible interfaces.

PMID- 27882972
TI  - Emergent phenomena induced by spin-orbit coupling at surfaces and interfaces.
AB  - Spin-orbit coupling (SOC) describes the relativistic interaction between the spin
      and momentum degrees of freedom of electrons, and is central to the rich
      phenomena observed in condensed matter systems. In recent years, new phases of
      matter have emerged from the interplay between SOC and low dimensionality, such
      as chiral spin textures and spin-polarized surface and interface states. These
      low-dimensional SOC-based realizations are typically robust and can be exploited
      at room temperature. Here we discuss SOC as a means of producing such
      fundamentally new physical phenomena in thin films and heterostructures. We put
      into context the technological promise of these material classes for developing
      spin-based device applications at room temperature.

PMID- 27882974
TI  - United Kingdom: Illness should not curtail PhD funding.

PMID- 27882977
TI  - Correction.

PMID- 27882975
TI  - Ephrin Bs and canonical Reelin signalling.

PMID- 27882978
TI  - Nanoscience: Flexible graphene strengthens friction.

PMID- 27882980
TI  - Developmental biology: 'Mini-guts' made with nerves.

PMID- 27882976
TI  - Doped polymer semiconductors with ultrahigh and ultralow work functions for ohmic
      contacts.
AB  - To make high-performance semiconductor devices, a good ohmic contact between the
      electrode and the semiconductor layer is required to inject the maximum current
      density across the contact. Achieving ohmic contacts requires electrodes with
      high and low work functions to inject holes and electrons respectively, where the
      work function is the minimum energy required to remove an electron from the Fermi
      level of the electrode to the vacuum level. However, it is challenging to produce
      electrically conducting films with sufficiently high or low work functions,
      especially for solution-processed semiconductor devices. Hole-doped polymer
      organic semiconductors are available in a limited work-function range, but hole
      doped materials with ultrahigh work functions and, especially, electron-doped
      materials with low to ultralow work functions are not yet available. The key
      challenges are stabilizing the thin films against de-doping and suppressing
      dopant migration. Here we report a general strategy to overcome these limitations
      and achieve solution-processed doped films over a wide range of work functions
      (3.0-5.8 electronvolts), by charge-doping of conjugated polyelectrolytes and then
      internal ion-exchange to give self-compensated heavily doped polymers. Mobile
      carriers on the polymer backbone in these materials are compensated by covalently
      bonded counter-ions. Although our self-compensated doped polymers superficially
      resemble self-doped polymers, they are generated by separate charge-carrier
      doping and compensation steps, which enables the use of strong dopants to access
      extreme work functions. We demonstrate solution-processed ohmic contacts for high
      performance organic light-emitting diodes, solar cells, photodiodes and
      transistors, including ohmic injection of both carrier types into polyfluorene
      the benchmark wide-bandgap blue-light-emitting polymer organic semiconductor. We
      also show that metal electrodes can be transformed into highly efficient hole-
      and electron-injection contacts via the self-assembly of these doped
      polyelectrolytes. This consequently allows ambipolar field-effect transistors to
      be transformed into high-performance p- and n-channel transistors. Our strategy
      provides a method for producing ohmic contacts not only for organic
      semiconductors, but potentially for other advanced semiconductors as well,
      including perovskites, quantum dots, nanotubes and two-dimensional materials.

PMID- 27882979
TI  - Contesting the massacre at Nataruk.

PMID- 27882982
TI  - Microbiome: Low-fibre diet puts gut at risk.

PMID- 27882981
TI  - Trump: threats to space science?

PMID- 27882983
TI  - The power of big data must be harnessed for medical progress.

PMID- 27882984
TI  - Immigrant and minority scientists shaken by Trump win.

PMID- 27882985
TI  - Brazil's scientists battle to escape 20-year funding freeze.

PMID- 27882986
TI  - First Middle Eastern X-ray factory readies for action.

PMID- 27882987
TI  - Fire up the atom forge.

PMID- 27882988
TI  - Rock core from dinosaur-killing impact reveals how enormous craters form.

PMID- 27882989
TI  - US Cancer Moonshot must strike a balance between research and prevention.

PMID- 27882990
TI  - Malaria vaccine, peatland protection and a string of satellites.

PMID- 27882991
TI  - Print flexible solar cells.

PMID- 27882992
TI  - Middle East X-ray factory is a source of hope.

PMID- 27882993
TI  - Geneticists hope to unlock secrets of bats' complex sounds.

PMID- 27882994
TI  - Stand firm on hormone disruptors.

PMID- 27882995
TI  - The sparrow with four sexes.

PMID- 27882996
TI  - CRISPR gene-editing tested in a person for the first time.

PMID- 27882997
TI  - Development of a validated algorithm for the diagnosis of paediatric asthma in
      electronic medical records.
AB  - An accurate estimation of the prevalence of paediatric asthma in Alberta and
      elsewhere is hampered by uncertainty regarding disease definition and diagnosis.
      Electronic medical records (EMRs) provide a rich source of clinical data from
      primary-care practices that can be used in better understanding the occurrence of
      the disease. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN)
      database includes cleaned data extracted from the EMRs of primary-care
      practitioners. The purpose of the study was to develop and validate a case
      definition of asthma in children 1-17 who consult family physicians, in order to
      provide primary-care estimates of childhood asthma in Alberta as accurately as
      possible. The validation involved the comparison of the application of a
      theoretical algorithm (to identify patients with asthma) to a physician review of
      records included in the CPCSSN database (to confirm an accurate diagnosis). The
      comparison yielded 87.4% sensitivity, 98.6% specificity and a positive and
      negative predictive value of 91.2% and 97.9%, respectively, in the age group 1-17
      years. The algorithm was also run for ages 3-17 and 6-17 years, and was found to
      have comparable statistical values. Overall, the case definition and algorithm
      yielded strong sensitivity and specificity metrics and was found valid for use in
      research in CPCSSN primary-care practices. The use of the validated asthma
      algorithm may improve insight into the prevalence, diagnosis, and management of
      paediatric asthma in Alberta and Canada.

PMID- 27883000
TI  - Corrigendum: Exposure to Sound Vibrations Lead to Transcriptomic, Proteomic and
      Hormonal Changes in Arabidopsis.

PMID- 27882998
TI  - Dopamine and Opioid Neurotransmission in Behavioral Addictions: A Comparative PET
      Study in Pathological Gambling and Binge Eating.
AB  - Although behavioral addictions share many clinical features with drug addictions,
      they show strikingly large variation in their behavioral phenotypes (such as in
      uncontrollable gambling or eating). Neurotransmitter function in behavioral
      addictions is poorly understood, but has important implications in understanding
      its relationship with substance use disorders and underlying mechanisms of
      therapeutic efficacy. Here, we compare opioid and dopamine function between two
      behavioral addiction phenotypes: pathological gambling (PG) and binge eating
      disorder (BED). Thirty-nine participants (15 PG, 7 BED, and 17 controls) were
      scanned with [11C]carfentanil and [18F]fluorodopa positron emission tomography
      using a high-resolution scanner. Binding potentials relative to non-displaceable
      binding (BPND) for [11C]carfentanil and influx rate constant (Ki) values for
      [18F]fluorodopa were analyzed with region-of-interest and whole-brain voxel-by
      voxel analyses. BED subjects showed widespread reductions in [11C]carfentanil
      BPND in multiple subcortical and cortical brain regions and in striatal
      [18F]fluorodopa Ki compared with controls. In PG patients, [11C]carfentanil BPND
      was reduced in the anterior cingulate with no differences in [18F]fluorodopa Ki
      compared with controls. In the nucleus accumbens, a key region involved in reward
      processing, [11C]Carfentanil BPND was 30-34% lower and [18F]fluorodopa Ki was 20%
      lower in BED compared with PG and controls (p<0.002). BED and PG are thus
      dissociable as a function of dopaminergic and opioidergic neurotransmission.
      Compared with PG, BED patients show widespread losses of mu-opioid receptor
      availability together with presynaptic dopaminergic defects. These findings
      highlight the heterogeneity underlying the subtypes of addiction and indicate
      differential mechanisms in the expression of pathological behaviors and responses
      to treatment.

PMID- 27882999
TI  - Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive
      Motivation.
AB  - Obesity is primarily due to food intake in excess of the body's energetic
      requirements, intake that is not only associated with hunger but also the
      incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a
      target for the treatment of human obesity. Mechanistically, 5-HT2CRs are
      positioned to influence both homeostatic feeding circuits within the hypothalamus
      and reward circuits within the ventral tegmental area (VTA). Here we investigated
      the role of 5-HT2CRs in incentive motivation using a mathematical model of
      progressive ratio (PR) responding in mice. We found that the 5-HT2CR agonist
      lorcaserin significantly reduced both ad libitum chow intake and PR responding
      for chocolate pellets and increased c-fos expression in VTA 5-HT2CR expressing
      gamma-aminobutyric acid (GABA) neurons, but not 5-HT2CR expressing dopamine (DA)
      neurons. We next adopted a chemogenetic approach using a 5-HT2CRCRE line to
      clarify the function of subset of 5-HT2C receptor expressing VTA neurons in the
      modulation of appetite and food-motivated behavior. Activation of VTA 5-HT2C
      receptor expressing neurons significantly reduced ad libitum chow intake, operant
      responding for chocolate pellets, and the incentive value of food. In contrast,
      chemogenetic inhibition of VTA 5-HT2C receptor expressing neurons had no effect
      on the feeding behavior. These results indicate that activation of the
      subpopulation of 5-HT2CR neurons within the VTA is sufficient to significantly
      reduce homeostatic feeding and effort-based intake of palatable food, and that
      this subset has an inhibitory role in motivational processes. These findings are
      relevant to the treatment of obesity.

PMID- 27883001
TI  - Psoriasis.
AB  - Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic
      manifestations and substantial negative effects on patient quality of life.
      Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately
      half of the accountable genetic effect of psoriasis maps to the major
      histocompatibility complex, >70 other loci have been identified, many of which
      implicate nuclear factor-kappaB, interferon signalling and the IL-23-IL-23
      receptor axis. Psoriasis pathophysiology is characterized by abnormal
      keratinocyte proliferation and immune cell infiltration in the dermis and
      epidermis involving the innate and adaptive immune systems, with important roles
      for dendritic cells and T cells, among other cells. Frequent comorbidities are
      rheumatological and cardiovascular in nature, in particular, psoriatic arthritis.
      Current treatments for psoriasis include topical agents, photo-based therapies,
      traditional systemic drugs and biologic agents. Treatments can be used in
      combination or as monotherapy. Biologic therapies that target specific disease
      mediators have become a mainstay in the treatment of moderate-to-severe disease,
      whereas advances in the treatment of mild-to-moderate disease have been limited.

PMID- 27883004
TI  - Psoriasis.

PMID- 27883002
TI  - A randomised open-label cross-over study of inhaler errors, preference and time
      to achieve correct inhaler use in patients with COPD or asthma: comparison of
      ELLIPTA with other inhaler devices.
AB  - Errors in the use of different inhalers were investigated in patients naive to
      the devices under investigation in a multicentre, single-visit, randomised, open
      label, cross-over study. Patients with chronic obstructive pulmonary disease
      (COPD) or asthma were assigned to ELLIPTA vs DISKUS (Accuhaler), metered-dose
      inhaler (MDI) or Turbuhaler. Patients with COPD were also assigned to ELLIPTA vs
      Handihaler or Breezhaler. Patients demonstrated inhaler use after reading the
      patient information leaflet (PIL). A trained investigator assessed critical
      errors (i.e., those likely to result in the inhalation of significantly reduced,
      minimal or no medication). If the patient made errors, the investigator
      demonstrated the correct use of the inhaler, and the patient demonstrated inhaler
      use again. Fewer COPD patients made critical errors with ELLIPTA after reading
      the PIL vs: DISKUS, 9/171 (5%) vs 75/171 (44%); MDI, 10/80 (13%) vs 48/80 (60%);
      Turbuhaler, 8/100 (8%) vs 44/100 (44%); Handihaler, 17/118 (14%) vs 57/118 (48%);
      Breezhaler, 13/98 (13%) vs 45/98 (46%; all P<0.001). Most patients (57-70%) made
      no errors using ELLIPTA and did not require investigator instruction. Instruction
      was required for DISKUS (65%), MDI (85%), Turbuhaler (71%), Handihaler (62%) and
      Breezhaler (56%). Fewer asthma patients made critical errors with ELLIPTA after
      reading the PIL vs: DISKUS (3/70 (4%) vs 9/70 (13%), P=0.221); MDI (2/32 (6%) vs
      8/32 (25%), P=0.074) and significantly fewer vs Turbuhaler (3/60 (5%) vs 20/60
      (33%), P<0.001). More asthma and COPD patients preferred ELLIPTA over the other
      devices (all P?0.002). Significantly, fewer COPD patients using ELLIPTA made
      critical errors after reading the PIL vs other inhalers. More asthma and COPD
      patients preferred ELLIPTA over comparator inhalers.

PMID- 27883005
TI  - Surgery: Single vs bilateral artery grafts.

PMID- 27883006
TI  - Dyslipidaemia: Apo-AI infusion after acute MI.

PMID- 27883003
TI  - Opportunities to develop the professional role of community pharmacists in the
      care of patients with asthma: a cross-sectional study.
AB  - There are many indications in Australia and globally that asthma management is
      suboptimal. Ideally, patients need to proactively self-manage the condition with
      the support of health professionals. Community pharmacists are a highly
      accessible resource for patients but currently provide inconsistent services.
      General practitioners also face many barriers to the provision of chronic disease
      management for asthma patients. The aim of this research was to characterise
      patients with asthma who present to community pharmacy. The objective was to
      identify opportunities to develop the role of pharmacists in the context of the
      primary healthcare setting and in view of the needs of the patients they
      routinely encounter. The results of a comprehensive survey of 248 patients
      recruited from community pharmacies indicated there was discordance between
      patient perceptions of asthma control and actual asthma control. Almost half the
      patients surveyed had poorly controlled asthma, whereas almost three quarters
      perceived their asthma to be well or completely controlled. Fewer than 20% of
      patients were utilising written asthma action plans, and issues around quality
      use of medicines were identified. The significance of the incongruent perceptions
      regarding asthma control is that patients are unlikely to proactively seek
      intervention and support from healthcare professionals. Community pharmacists
      provide a significant opportunity to address these issues by direct intervention.
      There is scope to investigate pharmacists preparing written asthma action plans
      for patients, using software to monitor medication adherence and prescribe on
      going medication. To maximise the potential of pharmacists, barriers to practice
      need to be identified and addressed.

PMID- 27883007
TI  - Coronary artery disease: Nature versus nurture in coronary atherosclerosis.

PMID- 27883008
TI  - Habitat-driven variation in mycorrhizal communities in the terrestrial orchid
      genus Dactylorhiza.
AB  - Orchid species are critically dependent on mycorrhizal fungi for completion of
      their life cycle, particularly during the early stages of their development when
      nutritional resources are scarce. As such, orchid mycorrhizal fungi play an
      important role in the population dynamics, abundance, and spatial distribution of
      orchid species. However, less is known about the ecology and distribution of
      orchid mycorrhizal fungi. In this study, we used 454 amplicon pyrosequencing to
      investigate ecological and geographic variation in mycorrhizal associations in
      fourteen species of the orchid genus Dactylorhiza. More specifically, we tested
      the hypothesis that variation in orchid mycorrhizal communities resulted
      primarily from differences in habitat conditions where the species were growing.
      The results showed that all investigated Dactylorhiza species associated with a
      large number of fungal OTUs, the majority belonging to the Tulasnellaceae,
      Ceratobasidiaceae and Sebacinales. Mycorrhizal specificity was low, but
      significant variation in mycorrhizal community composition was observed between
      species inhabiting different ecological habitats. Although several fungi had a
      broad geographic distribution, Species Indicator Analysis revealed some fungi
      that were characteristic for specific habitats. Overall, these results indicate
      that orchid mycorrhizal fungi may have a broad geographic distribution, but that
      their occurrence is bounded by specific habitat conditions.

PMID- 27883010
TI  - Measles virus induces persistent infection by autoregulation of viral
      replication.
AB  - Natural infection with measles virus (MV) establishes lifelong immunity.
      Persistent infection with MV is likely involved in this phenomenon, as non
      replicating protein antigens never induce such long-term immunity. Although MV
      establishes stable persistent infection in vitro and possibly in vivo, the
      mechanism by which this occurs is largely unknown. Here, we demonstrate that MV
      changes the infection mode from lytic to non-lytic and evades the innate immune
      response to establish persistent infection without viral genome mutation. We
      found that, in the persistent phase, the viral RNA level declined with the
      termination of interferon production and cell death. Our analysis of viral
      protein dynamics shows that during the establishment of persistent infection, the
      nucleoprotein level was sustained while the phosphoprotein and large protein
      levels declined. The ectopic expression of nucleoprotein suppressed viral
      replication, indicating that viral replication is self-regulated by nucleoprotein
      accumulation during persistent infection. The persistently infected cells were
      able to produce interferon in response to poly I:C stimulation, suggesting that
      MV does not interfere with host interferon responses in persistent infection. Our
      results may provide mechanistic insight into the persistent infection of this
      cytopathic RNA virus that induces lifelong immunity.

PMID- 27883009
TI  - Bumble bee parasite strains vary in resistance to phytochemicals.
AB  - Nectar and pollen contain diverse phytochemicals that can reduce disease in
      pollinators. However, prior studies showed variable effects of nectar chemicals
      on infection, which could reflect variable phytochemical resistance among
      parasite strains. Inter-strain variation in resistance could influence
      evolutionary interactions between plants, pollinators, and pollinator disease,
      but testing direct effects of phytochemicals on parasites requires elimination of
      variation between bees. Using cell cultures of the bumble bee parasite Crithidia
      bombi, we determined (1) growth-inhibiting effects of nine floral phytochemicals
      and (2) variation in phytochemical resistance among four parasite strains. C.
      bombi growth was unaffected by naturally occurring concentrations of the known
      antitrypanosomal phenolics gallic acid, caffeic acid, and chlorogenic acid.
      However, C. bombi growth was inhibited by anabasine, eugenol, and thymol. Strains
      varied >3-fold in phytochemical resistance, suggesting that selection for
      phytochemical resistance could drive parasite evolution. Inhibitory
      concentrations of thymol (4.53-22.2 ppm) were similar to concentrations in Thymus
      vulgaris nectar (mean 5.2 ppm). Exposure of C. bombi to naturally occurring
      levels of phytochemicals-either within bees or during parasite transmission via
      flowers-could influence infection in nature. Flowers that produce antiparasitic
      phytochemicals, including thymol, could potentially reduce infection in Bombus
      populations, thereby counteracting a possible contributor to pollinator decline.

PMID- 27883011
TI  - Glass-Forming Tendency of Molecular Liquids and the Strength of the
      Intermolecular Attractions.
AB  - When we cool down a liquid below the melting temperature, it can either
      crystallize or become supercooled, and then form a disordered solid called glass.
      Understanding what makes a liquid to crystallize readily in one case and form a
      stable glass in another is a fundamental problem in science and technology. Here
      we show that the crystallization/glass-forming tendencies of the molecular
      liquids might be correlated with the strength of the intermolecular attractions,
      as determined from the combined experimental and computer simulation studies. We
      use van der Waals bonded propylene carbonate and its less polar structural analog
      3-methyl-cyclopentanone to show that the enhancement of the dipole-dipole forces
      brings about the better glass-forming ability of the sample when cooling from the
      melt. Our finding was rationalized by the mismatch between the optimal
      temperature range for the nucleation and crystal growth, as obtained for a
      modeled Lennard-Jones system with explicitly enhanced or weakened attractive part
      of the intermolecular 6-12 potential.

PMID- 27883013
TI  - Thermally induced magnetic relaxation in square artificial spin ice.
AB  - The properties of natural and artificial assemblies of interacting elements,
      ranging from Quarks to Galaxies, are at the heart of Physics. The collective
      response and dynamics of such assemblies are dictated by the intrinsic dynamical
      properties of the building blocks, the nature of their interactions and
      topological constraints. Here we report on the relaxation dynamics of the
      magnetization of artificial assemblies of mesoscopic spins. In our model nano
      magnetic system - square artificial spin ice - we are able to control the
      geometrical arrangement and interaction strength between the magnetically
      interacting building blocks by means of nano-lithography. Using time resolved
      magnetometry we show that the relaxation process can be described using the
      Kohlrausch law and that the extracted temperature dependent relaxation times of
      the assemblies follow the Vogel-Fulcher law. The results provide insight into the
      relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable
      energy and time scales, and demonstrates that these can serve as an ideal
      playground for the studies of collective dynamics and relaxations.

PMID- 27883014
TI  - First in-flight synchrotron X-ray absorption and photoemission study of carbon
      soot nanoparticles.
AB  - Many studies have been conducted on the environmental impacts of combustion
      generated aerosols. Due to their complex composition and morphology, their
      chemical reactivity is not well understood and new developments of analysis
      methods are needed. We report the first demonstration of in-flight X-ray based
      characterizations of freshly emitted soot particles, which is of paramount
      importance for understanding the role of one of the main anthropogenic
      particulate contributors to global climate change. Soot particles, produced by a
      burner for several air-to-fuel ratios, were injected through an aerodynamic lens,
      focusing them to a region where they interacted with synchrotron radiation. X-ray
      photoelectron spectroscopy and carbon K-edge near-edge X-ray absorption
      spectroscopy were performed and compared to those obtained for supported samples.
      A good agreement is found between these samples, although slight oxidation is
      observed for supported samples. Our experiments demonstrate that NEXAFS
      characterization of supported samples provides relevant information on soot
      composition, with limited effects of contamination or ageing under ambient
      storage conditions. The highly surface sensitive XPS experiments of airborne soot
      indicate that the oxidation is different at the surface as compared to the bulk
      probed by NEXAFS. We also report changes in soot's work function obtained at
      different combustion conditions.

PMID- 27883012
TI  - Immune signatures of protective spleen memory CD8 T cells.
AB  - Memory CD8 T lymphocyte populations are remarkably heterogeneous and differ in
      their ability to protect the host. In order to identify the whole range of
      qualities uniquely associated with protective memory cells we compared the gene
      expression signatures of two qualities of memory CD8 T cells sharing the same
      antigenic-specificity: protective (Influenza-induced, Flu-TM) and non-protective
      (peptide-induced, TIM) spleen memory CD8 T cells. Although Flu-TM and TIM express
      classical phenotypic memory markers and are polyfunctional, only Flu-TM protects
      against a lethal viral challenge. Protective memory CD8 T cells express a unique
      set of genes involved in migration and survival that correlate with their unique
      capacity to rapidly migrate within the infected lung parenchyma in response to
      influenza infection. We also enlighten a new set of poised genes expressed by
      protective cells that is strongly enriched in cytokines and chemokines such as
      Ccl1, Ccl9 and Gm-csf. CCL1 and GM-CSF genes are also poised in human memory CD8
      T cells. These immune signatures are also induced by two other pathogens
      (vaccinia virus and Listeria monocytogenes). The immune signatures associated
      with immune protection were identified on circulating cells, i.e. those that are
      easily accessible for immuno-monitoring and could help predict vaccines efficacy.

PMID- 27883015
TI  - MR Vascular Fingerprinting in Stroke and Brain Tumors Models.
AB  - In this study, we evaluated an MRI fingerprinting approach (MRvF) designed to
      provide high-resolution parametric maps of the microvascular architecture (i.e.,
      blood volume fraction, vessel diameter) and function (blood oxygenation)
      simultaneously. The method was tested in rats (n = 115), divided in 3 models:
      brain tumors (9 L, C6, F98), permanent stroke, and a control group of healthy
      animals. We showed that fingerprinting can robustly distinguish between healthy
      and pathological brain tissues with different behaviors in tumor and stroke
      models. In particular, fingerprinting revealed that C6 and F98 glioma models have
      similar signatures while 9 L present a distinct evolution. We also showed that it
      is possible to improve the results of MRvF and obtain supplemental information by
      changing the numerical representation of the vascular network. Finally, good
      agreement was found between MRvF and conventional MR approaches in healthy
      tissues and in the C6, F98, and permanent stroke models. For the 9 L glioma
      model, fingerprinting showed blood oxygenation measurements that contradict
      results obtained with a quantitative BOLD approach. In conclusion, MR vascular
      fingerprinting seems to be an efficient technique to study microvascular
      properties in vivo. Multiple technical improvements are feasible and might
      improve diagnosis and management of brain diseases.

PMID- 27883016
TI  - Sexual display complexity varies non-linearly with age and predicts breeding
      status in greater flamingos.
AB  - The long-lived greater flamingo (Phoenicopterus roseus) is famous for performing
      conspicuous group displays during which adults try to acquire a new mate each
      year with varying success. We examined variation in the sexual display complexity
      (SDC) of wild flamingos aged between 4 and 37 yrs. SDC was defined as the product
      of richness (the number of different display movements) and versatility (the
      number of transitions between movements) within a 5 min behavioral sequence. In
      both sexes, date in the pairing season had a linear and positive effect on SDC,
      whereas age had a quadratic effect, with SDC increasing until about age 20yrs,
      and declining afterwards. SDC better explained pairing patterns than age, and
      positively influenced the probability of becoming a breeder. Our results thus
      support the idea that SDC is an honest signal of individual quality and further
      suggest that senescence in display could be an overlooked aspect of reproductive
      decline in species with no or weak pair bonding.

PMID- 27883017
TI  - Differential neural encoding of sensorimotor and visual body representations.
AB  - Sensorimotor processing specifically impacts mental body representations. In
      particular, deteriorated somatosensory input (as after complete spinal cord
      injury) increases the relative weight of visual aspects of body parts'
      representations, leading to aberrancies in how images of body parts are mentally
      manipulated (e.g. mental rotation). This suggests that a sensorimotor or visual
      reference frame, respectively, can be relatively dominant in local (hands) versus
      global (full-body) bodily representations. On this basis, we hypothesized that
      the recruitment of a specific reference frame could be reflected in the
      activation of sensorimotor versus visual brain networks. To this aim, we directly
      compared the brain activity associated with mental rotation of hands versus full
      bodies. Mental rotation of hands recruited more strongly the supplementary motor
      area, premotor cortex, and secondary somatosensory cortex. Conversely, mental
      rotation of full-bodies determined stronger activity in temporo-occipital
      regions, including the functionally-localized extrastriate body area. These
      results support that (1) sensorimotor and visual frames of reference are used to
      represent the body, (2) two distinct brain networks encode local or global bodily
      representations, and (3) the extrastriate body area is a multimodal region
      involved in body processing both at the perceptual and representational level.

PMID- 27883018
TI  - Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro
      model.
AB  - Isothiocyanates are the most intensively studied breakdown products of
      glucosinolates from Brassica plants and well recognized for their pleiotropic
      effects against cancer but also for their genotoxic potential. However, knowledge
      about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As
      determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as
      breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary
      murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of
      nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the
      genotoxic potential of nitriles was found to be comparable to isothiocyanates.
      DNA damage was persistent over a certain time period and CYP2E1-overexpression
      further increased the genotoxic potential of the nitriles. Based on actual in
      vitro data, no indications are given that food-borne nitriles could be relevant
      for cancer prevention, but could pose a certain genotoxic risk under conditions
      relevant for food consumption.

PMID- 27883019
TI  - 17-oxo-DHA displays additive anti-inflammatory effects with fluticasone
      propionate and inhibits the NLRP3 inflammasome.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung
      function associated with increased local and systemic inflammatory markers, such
      as TNFalpha and IL-1beta. Glucocorticoids are used to treat this chronic disease,
      however their efficacy is low and new drugs are very much required. 17-oxo-DHA is
      a cyclooxygenase-2-dependent, electrophilic, alpha,beta-unsaturated keto
      derivative of docosahexaenoic acid with anti-inflammatory properties. We
      evaluated the action of 17-oxo-DHA alone or in combination with the steroid
      fluticasone propionate (FP) in peripheral blood mononuclear cells (PBMCs) from
      COPD patients and healthy individuals exposed to lipopolysaccharide. We show that
      PBMCs from COPD patients released higher levels of TNFalpha and IL-1beta compared
      to controls. 17-oxo-DHA displayed strong anti-inflammatory effects. The addition
      of 17-oxo-DHA in combination with FP showed enhanced anti-inflammatory effects
      through the modulation of transcriptional and post-transcriptional mechanisms. 17
      oxo-DHA, but not FP, was able to suppress the release of mature IL-1beta through
      inhibition of the NLRP3 inflammasome. Furthermore, 17-oxo-DHA inhibited
      inflammasome-dependent degradation of the glucocorticoid receptor (GR). Our
      findings suggest that 17-oxo-DHA in combination with FP or other steroids might
      achieve higher therapeutic efficacy than steroids alone. Combined treatment might
      be particularly relevant in those conditions where increased inflammasome
      activation may lead to GR degradation and steroid-unresponsive inflammation.

PMID- 27883020
TI  - CHFR negatively regulates SIRT1 activity upon oxidative stress.
AB  - SIRT1, the NAD+-dependent protein deacetylase, controls cell-cycle progression
      and apoptosis by suppressing p53 tumour suppressor. Although SIRT1 is known to be
      phosphorylated by JNK1 upon oxidative stress and subsequently down-regulated, it
      still remains elusive how SIRT1 stability and activity are controlled. Here, we
      have unveiled that CHFR functions as an E3 Ub-ligase of SIRT1, responsible for
      its proteasomal degradation under oxidative stress conditions. CHFR interacts
      with and destabilizes SIRT1 by ubiquitylation and subsequent proteolysis. Such
      CHFR-mediated SIRT1 inhibition leads to the increase of p53 acetylation and its
      target gene transcription. Notably, CHFR facilitates SIRT1 destabilization when
      SIRT1 is phosphorylated by JNK1 upon oxidative stress, followed by prominent
      apoptotic cell death. Meanwhile, JNK inhibitor prevents SIRT1 phosphorylation,
      leading to elevated SIRT1 protein levels even in the presence of H2O2. Taken
      together, our results indicate that CHFR plays a crucial role in the cellular
      stress response pathway by controlling the stability and function of SIRT1.

PMID- 27883021
TI  - Identification of aberrant tRNA-halves expression patterns in clear cell renal
      cell carcinoma.
AB  - Small non-coding RNAs (sncRNA; <200 nt) regulate various cellular processes and
      modify gene expression. Under nutritional, biological or physiochemical stress
      some mature sncRNAs (e.g. tRNAs) are cleaved into halves (30-50 nt) and smaller
      fragments (18-22 nt); the significance and functional role of these tRNA
      fragments is unknown, but their existence has been linked to carcinogenesis. We
      used small RNA sequencing to determine the expression of sncRNAs. Subsequently
      the findings were validated for miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC using
      qPCR. We identified differential expression of 132 miRNAs (upregulated: 61,
      downregulated: 71) and 32 tRNAs (upregulated: 13, downregulated: 19). Read length
      analysis showed that miRNAs mapped in the 20-24 nt fraction, whereas tRNA reads
      mapped in the 30-36 nt fraction instead the expected size of 73-95 nt thereby
      indicating cleavage of tRNAs. Overexpression of miR-122-5p and miR-142-3p as well
      as downregulation of 5'tRNA4-Val-AAC was validated in an independent cohort of
      118 ccRCC and 74 normal renal tissues. Furthermore, staging and grading was
      inversely correlated with the 5'tRNA4-Val-AAC expression. Serum levels of miR-122
      5p, miR-142-3p and 5'tRNA4-Val-AAC did not differ in ccRCC and control subjects.
      In conclusion, 5' cleavage of tRNAs occurs in ccRCC, but the exact functional
      implication of tRNA-halve deregulation remains to be clarified.

PMID- 27883024
TI  - Lower Vitamin D Metabolites Levels Were Associated With Increased Coronary Artery
      Diseases in Type 2 Diabetes Patients in India.
AB  - The purpose of the present study was to measure six vitamin D metabolites and to
      find the association between vitamin D deficiency and coronary artery diseases in
      diabetes (T2DM_CAD). Four groups [control (n = 50), type 2 diabetes (T2DM, n =
      71), coronary artery diseases (CAD, n = 28), T2DM_CAD (n = 38)] of total 187
      subjects were included in the study. Six vitamin D metabolites (D2, D3, 25(OH)D2,
      25(OH)D3, 1,25(OH)2D2, 1,25(OH)2D3), total 25(OH)D and total 1,25(OH)2D were
      measured by UPLC/APCI/HRMS method in these subjects. Although all the vitamin D
      metabolites were significantly decreased in T2DM_CAD as compared to both control
      and T2DM subjects (p < 0.05), only two metabolites i.e., 25(OH)D3 and total
      25(OH)D were significantly (p < 0.05) decreased in the T2DM subjects as compared
      with the control subjects (p < 0.05). Vitamin D3, 1,25(OH)2D2, 25(OH)D, and
      1,25(OH)2D levels were significantly decreased in T2DM_CAD subjects as compared
      with CAD subjects (p < 0.05). Further, multiple logistic regression analysis
      revealed that total 25(OH)D and total 1,25(OH)2D can be used to predict T2DM (OR
      0.82.95% CI 0.68-0.99; p = 0.0208) and T2DM with CAD (OR 0.460, 95% CI 0.242
      0.874; p = 0.0177), respectively. Our data concludes that lower concentration of
      1,25(OH)2D is associated with type 2 diabetes coexisting with coronary artery
      diseases in South Indian subjects.

PMID- 27883022
TI  - High expression of GNA13 is associated with poor prognosis in hepatocellular
      carcinoma.
AB  - Guanine nucleotide binding protein alpha 13 (GNA13) has been found to play
      critical roles in the development of several human cancers. However, little is
      known about GNA13 expression and its clinical significance in hepatocellular
      carcinoma (HCC). In our study, GNA13 was reported to be significantly up
      regulated in HCC tissues, and this was correlated with several
      clinicopathological parameters, including tumor multiplicity (P = 0.004), TNM
      stage (P = 0.002), and BCLC stage (P = 0.010). Further Cox regression analysis
      suggested that GNA13 expression was an independent prognostic factor for overall
      survival (P = 0.014) and disease-free survival (P = 0.005). Moreover, we found
      that overexpression of GNA13 couldn't promote cell proliferation in vitro, but
      could significantly increase the invasion ability of HCC cells. Together, our
      study demonstrates GNA13 may be served as a prognostic biomarker for HCC patients
      after curative hepatectomy, in which high expression of GNA13 suggests poor
      prognosis of HCC patients.

PMID- 27883023
TI  - A comparison of the performance of molecularly imprinted polymer nanoparticles
      for small molecule targets and antibodies in the ELISA format.
AB  - Here we show that molecularly imprinted polymer nanoparticles, prepared in
      aqueous media by solid phase synthesis with immobilised L-thyroxine, glucosamine,
      fumonisin B2 or biotin as template, can demonstrate comparable or better
      performance to commercially produced antibodies in enzyme-linked competitive
      assays. Imprinted nanoparticles-based assays showed detection limits in the pM
      range and polymer-coated microplates are stable to storage at room temperature
      for at least 1 month. No response to analyte was detected in control experiments
      with nanoparticles imprinted with an unrelated template (trypsin) but prepared
      with the same polymer composition. The ease of preparation, high affinity of
      solid-phase synthesised imprinted nanoparticles and the lack of requirement for
      cold chain logistics make them an attractive alternative to traditional
      antibodies for use in immunoassays.

PMID- 27883025
TI  - MathIOmica: An Integrative Platform for Dynamic Omics.
AB  - Multiple omics data are rapidly becoming available, necessitating the use of new
      methods to integrate different technologies and interpret the results arising
      from multimodal assaying. The MathIOmica package for Mathematica provides one of
      the first extensive introductions to the use of the Wolfram Language to tackle
      such problems in bioinformatics. The package particularly addresses the necessity
      to integrate multiple omics information arising from dynamic profiling in a
      personalized medicine approach. It provides multiple tools to facilitate
      bioinformatics analysis, including importing data, annotating datasets, tracking
      missing values, normalizing data, clustering and visualizing the classification
      of data, carrying out annotation and enumeration of ontology memberships and
      pathway analysis. We anticipate MathIOmica to not only help in the creation of
      new bioinformatics tools, but also in promoting interdisciplinary investigations,
      particularly from researchers in mathematical, physical science and engineering
      fields transitioning into genomics, bioinformatics and omics data integration.

PMID- 27883027
TI  - Disturbed phospholipid homeostasis in endoplasmic reticulum initiates tri-o
      cresyl phosphate-induced delayed neurotoxicity.
AB  - Tri-o-cresyl phosphate (TOCP) is a widely used organophosphorus compound, which
      can cause a neurodegenerative disorder, i.e., organophosphate-induced delayed
      neurotoxicity (OPIDN). The biochemical events in the initiation of OPIDN were not
      fully understood except for the essential inhibition of neuropathy target
      esterase (NTE). NTE, located in endoplasmic reticulum (ER), catalyzes the
      deacylation of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) to
      glycerophosphocholine (GPC). The present study aims to study the changes of ER
      phospholipids profile as well as levels of important intermediates of
      phospholipid synthesis such as diacylglycerol (DAG) and phosphatidic acid (PA) at
      the initiation stage of OPIDN. Hens are the most commonly used animal models of
      OPIDN. The spinal cord phospholipidomic profiles of hens treated by TOCP were
      studied by using HPLC-MS-MS. The results revealed that TOCP induced an increase
      of PC, LPC, and sphingomyelin (SM) levels and a decrease of GPC,
      phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE),
      lysophosphatidylserine (LPS), phosphatidylglycerol (PG), and phosphatidylinositol
      (PI) levels., Levels of DAG and PA were also decreased. Pretreatment with
      phenylmethylsulfonyl fluoride (PMSF) 24 h before TOCP administration prevented
      OPIDN and restored the TOCP-induced changes of phospholipids except GPC. Thus,
      the disruption of ER phospholipid homeostasis may contribute to the initiation of
      organophosphate-induced delayed neurotoxicity.

PMID- 27883028
TI  - Ultra-wideband filtering of spoof surface plasmon polaritons using deep
      subwavelength planar structures.
AB  - Novel ultra-wideband filtering of spoof surface plasmon polaritons (SPPs) is
      proposed in the microwave frequency using deep subwavelength planar structures
      printed on thin and flexible dielectric substrate. The proposed planar SPPs
      waveguide is composed of two mirror-oriented metallic corrugated strips, which
      are further decorated with parallel-arranged slots in the main corrugated strips.
      This compound structure provides deep subwavelength field confinement as well as
      flexible parameters when employed as a plasmonic waveguide, which is potential to
      construct miniaturization. Using momentum and impedance matching technology, we
      achieve a smooth conversion between the proposed SPPs waveguide and the
      conventional transmission line. To verify the validity of the design, we
      fabricate a spoof SPPs filter, and the measured results illustrate excellent
      performance, in which the reflection coefficient is less than -10 dB within the 
      3 dB passband from 1.21 GHz to 7.21 GHz with the smallest insertion loss of 1.23
      dB at 2.21 GHz, having very good agreements with numerical simulations. The ultra
      wideband filter with low insertion loss and high transmission efficiency
      possesses great potential in modern communication systems.

PMID- 27883029
TI  - Helicity within the vortex filament model.
AB  - Kinetic helicity is one of the invariants of the Euler equations that is
      associated with the topology of vortex lines within the fluid. In superfluids,
      the vorticity is concentrated along vortex filaments. In this setting, helicity
      would be expected to acquire its simplest form. However, the lack of a core
      structure for vortex filaments appears to result in a helicity that does not
      retain its key attribute as a quadratic invariant. By defining a spanwise vector
      to the vortex through the use of a Seifert framing, we are able to introduce
      twist and henceforth recover the key properties of helicity. We present several
      examples for calculating internal twist to illustrate why the centreline helicity
      alone will lead to ambiguous results if a twist contribution is not introduced.
      Our choice of the spanwise vector can be expressed in terms of the tangential
      component of velocity along the filament. Since the tangential velocity does not
      alter the configuration of the vortex at later times, we are able to recover a
      similar equation for the internal twist angle to that of classical vortex tubes.
      Our results allow us to explain how a quasi-classical limit of helicity emerges
      from helicity considerations for individual superfluid vortex filaments.

PMID- 27883026
TI  - Inhibition of lysophosphatidic acid receptors 1 and 3 attenuates atherosclerosis
      development in LDL-receptor deficient mice.
AB  - Lysophosphatidic acid (LPA) is a natural lysophospholipid present at high
      concentrations within lipid-rich atherosclerotic plaques. Upon local accumulation
      in the damaged vessels, LPA can act as a potent activator for various types of
      immune cells through its specific membrane receptors LPA1/3. LPA elicits
      chemotactic, pro-inflammatory and apoptotic effects that lead to atherosclerotic
      plaque progression. In this study we aimed to inhibit LPA signaling by means of
      LPA1/3 antagonism using the small molecule Ki16425. We show that LPA1/3
      inhibition significantly impaired atherosclerosis progression. Treatment with
      Ki16425 also resulted in reduced CCL2 production and secretion, which led to less
      monocyte and neutrophil infiltration. Furthermore, we provide evidence that
      LPA1/3 blockade enhanced the percentage of non-inflammatory, Ly6Clow monocytes
      and CD4+ CD25+ FoxP3+ T-regulatory cells. Finally, we demonstrate that LPA1/3
      antagonism mildly reduced plasma LDL cholesterol levels. Therefore,
      pharmacological inhibition of LPA1/3 receptors may prove a promising approach to
      diminish atherosclerosis development.

PMID- 27883031
TI  - Transition from glass- to gel-like states in clay at a liquid interface.
AB  - Colloidal clay in water suspensions are known to exhibit a multitude of bulk
      phases depending on initial colloidal concentration and ionic strength, and
      examples of this include repulsive Wigner colloidal glasses at low ionic strength
      and attractive gels at higher ionic strength due to screened electrostatic forces
      by the electrolyte. From confocal Raman microscopy combined with elasticity
      measurements, we infer that clay trapped at quasi two-dimensional interfaces
      between oil and water also exhibit confined glass-like or gel-like states. The
      results can be important for the preparation of particles stabilized colloidal
      emulsions or colloidal capsules, and a better understanding of this phenomenon
      may lead to new emulsion or encapsulation technologies.

PMID- 27883032
TI  - Thermodynamic origin of instability in hybrid halide perovskites.
AB  - Degradation of hybrid halide perovskites under the influence of environmental
      factors impairs future prospects of using these materials as absorbers in solar
      cells. First principle calculations can be used as a guideline in search of new
      materials, provided we can rely on their predictive capabilities. We show that
      the instability of perovskites can be captured using ab initio total energy
      calculations for reactants and products augmented with additional thermodynamic
      data to account for finite temperature effects. Calculations suggest that the
      instability of CH3NH3PbI3 in moist environment is linked to the aqueous
      solubility of the CH3NH3I salt, thus making other perovskite materials with
      soluble decomposition products prone to degradation. Properties of NH3OHPbI3,
      NH3NH2PbI3, PH4PbI3, SbH4PbI3, CsPbBr3, and a new hypothetical SF3PbI3 perovskite
      are studied in the search for alternative solar cell absorber materials with
      enhanced chemical stability.

PMID- 27883030
TI  - Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis
      Mass Spectrometry Imaging.
AB  - Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been
      shown to be an effective tissue profiling and imaging technique, producing robust
      and reliable qualitative distribution images of an analyte or analytes in tissue
      sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a
      quantitative analytical technique by employing a mimetic tissue model previously
      shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to
      generate a viable and molecularly relevant control matrix for spiked drug
      standards which can be frozen, sectioned and subsequently analyzed for the
      generation of calibration curves to quantify unknown tissue section samples. The
      effects of extraction solvent composition, tissue thickness and solvent/tissue
      contact time were explored prior to any quantitative studies in order to optimize
      the LESA-MSI method across several different chemical entities. The use of a
      internal standard to normalize regional differences in ionization response across
      tissue sections was also investigated. Data are presented comparing quantitative
      results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue
      sections using DESI-MSI is also reported.

PMID- 27883033
TI  - Detecting and utilizing minority phases in heterogeneous catalysis.
AB  - Highly active phases in carbon monoxide oxidation are known, however they are
      transient in nature. Here, we determined for the first time the structure of such
      a highly active phase on platinum nanoparticles in an actual reactor. Unlike
      generally assumed, the surface of this phase is virtually free of adsorbates and
      co-exists with carbon-monoxide covered and surface oxidized platinum.
      Understanding the relation between gas composition and catalyst structure at all
      times and locations within a reactor enabled the rational design of a reactor
      concept, which maximizes the amount of the highly active phase and minimizes the
      amount of platinum needed.

PMID- 27883034
TI  - Questioning the Mpemba effect: hot water does not cool more quickly than cold.
AB  - The Mpemba effect is the name given to the assertion that it is quicker to cool
      water to a given temperature when the initial temperature is higher. This
      assertion seems counter-intuitive and yet references to the effect go back at
      least to the writings of Aristotle. Indeed, at first thought one might consider
      the effect to breach fundamental thermodynamic laws, but we show that this is not
      the case. We go on to examine the available evidence for the Mpemba effect and
      carry out our own experiments by cooling water in carefully controlled
      conditions. We conclude, somewhat sadly, that there is no evidence to support
      meaningful observations of the Mpemba effect.

PMID- 27883035
TI  - Telomeres are elongated in older individuals in a hibernating rodent, the edible
      dormouse (Glis glis).
AB  - Telomere shortening is thought to be an important biomarker for life history
      traits such as lifespan and aging, and can be indicative of genome integrity,
      survival probability and the risk of cancer development. In humans and other
      animals, telomeres almost always shorten with age, with more rapid telomere
      attrition in short-lived species. Here, we show that in the edible dormouse (Glis
      glis) telomere length significantly increases from an age of 6 to an age of 9
      years. While this finding could be due to higher survival of individuals with
      longer telomeres, we also found, using longitudinal measurements, a positive
      effect of age on the rate of telomere elongation within older individuals. To our
      knowledge, no previous study has reported such an effect of age on telomere
      lengthening. We attribute this exceptional pattern to the peculiar life-history
      of this species, which skips reproduction in years with low food availability.
      Further, we show that this "sit tight" strategy in the timing of reproduction is
      associated with an increasing likelihood for an individual to reproduce as it
      ages. As reproduction could facilitate telomere attrition, this life-history
      strategy may have led to the evolution of increased somatic maintenance and
      telomere elongation with increasing age.

PMID- 27883036
TI  - The mevalonate pathway regulates primitive streak formation via protein
      farnesylation.
AB  - The primitive streak in peri-implantation embryos forms the mesoderm and endoderm
      and controls cell differentiation. The metabolic cues regulating primitive streak
      formation remain largely unknown. Here we utilised a mouse embryonic stem (ES)
      cell differentiation system and a library of well-characterised drugs to identify
      these metabolic factors. We found that statins, which inhibit the mevalonate
      metabolic pathway, suppressed primitive streak formation in vitro and in vivo.
      Using metabolomics and pharmacologic approaches we identified the downstream
      signalling pathway of mevalonate and revealed that primitive streak formation
      requires protein farnesylation but not cholesterol synthesis. A tagging-via
      substrate approach revealed that nuclear lamin B1 and small G proteins were
      farnesylated in embryoid bodies and important for primitive streak gene
      expression. In conclusion, protein farnesylation driven by the mevalonate pathway
      is a metabolic cue essential for primitive streak formation.

PMID- 27883037
TI  - Ground states of a Bose-Einstein Condensate in a one-dimensional laser-assisted
      optical lattice.
AB  - We study the ground-state behavior of a Bose-Einstein Condensate (BEC) in a Raman
      laser-assisted one-dimensional (1D) optical lattice potential forming a
      multilayer system. We find that, such system can be described by an effective
      model with spin-orbit coupling (SOC) of pseudospin (N-1)/2, where N is the number
      of layers. Due to the intricate interplay between atomic interactions, SOC and
      laser-assisted tunnelings, the ground-state phase diagrams generally consist of
      three phases-a stripe, a plane wave and a normal phase with zero-momentum,
      touching at a quantum tricritical point. More important, even though the single
      particle states only minimize at zero-momentum for odd N, the many-body ground
      states may still develop finite momenta. The underlying mechanisms are
      elucidated. Our results provide an alternative way to realize an effective spin
      orbit coupling of Bose gas with the Raman-laser-assisted optical lattice, and
      would also be beneficial to the studies on SOC effects in spinor Bose systems
      with large spin.

PMID- 27883038
TI  - Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral
      vasospasm and brain injury after subarachnoid hemorrhage in rats.
AB  - Although delayed cerebral vasospasm (DCV) following subarachnoid hemorrhage (SAH)
      is closely related to the progression of brain damage, little is known about the
      molecular mechanism underlying its development. High mobility group box-1 (HMGB1)
      plays an important role as an initial inflammatory mediator in SAH. In this
      study, an SAH rat model was employed to evaluate the effects of anti-HMGB1
      monoclonal antibody (mAb) on DCV after SAH. A vasoconstriction of the basilar
      artery (BA) associated with a reduction of nuclear HMGB1 and its translocation in
      vascular smooth muscle cells were observed in SAH rats, and anti-HMGB1 mAb
      administration significantly suppressed these effects. Up-regulations of
      inflammation-related molecules and vasoconstriction-mediating receptors in the BA
      of SAH rats were inhibited by anti-HMGB1 mAb treatment. Anti-HMGB1 mAb attenuated
      the enhanced vasocontractile response to thrombin of the isolated BA from SAH
      rats and prevented activation of cerebrocortical microglia. Moreover, locomotor
      activity and weight loss recovery were also enhanced by anti-HMGB1 mAb
      administration. The vasocontractile response of the BA under SAH may be induced
      by events that are downstream of responses to HMGB1-induced inflammation and
      inhibited by anti-HMGB1 mAb. Anti-HMGB1 mAb treatment may provide a novel
      therapeutic strategy for DCV and early brain injury after SAH.

PMID- 27883042
TI  - Two novel viruses associated with the Apis mellifera pathogenic mite Varroa
      destructor.
AB  - Varroa destructor infestation of Apis mellifera colonies carries and/or promotes
      replication of honey bee viruses like the Deformed wing virus, the Varroa
      destructor virus-1, the Acute bee paralysis virus, the Israeli acute bee
      paralysis virus and the Kashmir bee virus that have been well described and
      characterized; but viruses exclusively associated with Varroa were not found. To
      look for viruses that may associate with- or infect V. destructor we performed
      deep sequencing (RNA-seq) of RNA extracted from honey bees and mites in Varroa
      infested untreated colonies. Comparative bioinformatic analysis of the two
      separate contig-assemblies generated from the sequences' reads annotated using
      Blastx enabled identification of new viruses unique to Varroa and absent in A.
      mellifera: an Iflavirus and a virus with homology to Ixodes scapularis associated
      virus 2, that we named Varroa destructor virus 2 (VDV-2) and 3(VDV-3),
      respectively. We validated these findings sequencing the mite- and honey bee
      viromes and in separate mites and honey bees randomly sampled. The complete
      genomes of VDV-2 and VDV-3 bear 9576 nucleotides and 4202 nucleotides,
      respectively. Phylogenetic analysis of VDV-3 suggests that it belongs to a new
      group of viruses. Our results open venues for investigating the pathogenicity of
      these V. destructor viruses.

PMID- 27883039
TI  - Structural and functional probing of PorZ, an essential bacterial surface
      component of the type-IX secretion system of human oral-microbiomic Porphyromonas
      gingivalis.
AB  - Porphyromonas gingivalis is a member of the human oral microbiome abundant in
      dysbiosis and implicated in the pathogenesis of periodontal (gum) disease. It
      employs a newly described type-IX secretion system (T9SS) for secretion of
      virulence factors. Cargo proteins destined for secretion through T9SS carry a
      recognition signal in the conserved C-terminal domain (CTD), which is removed by
      sortase PorU during translocation. Here, we identified a novel component of T9SS,
      PorZ, which is essential for surface exposure of PorU and posttranslational
      modification of T9SS cargo proteins. These include maturation of enzyme
      precursors, CTD removal and attachment of anionic lipopolysaccharide for
      anchorage in the outer membrane. The crystal structure of PorZ revealed two beta
      propeller domains and a C-terminal beta-sandwich domain, which conforms to the
      canonical CTD architecture. We further documented that PorZ is itself transported
      to the cell surface via T9SS as a full-length protein with its CTD intact,
      independently of the presence or activity of PorU. Taken together, our results
      shed light on the architecture and possible function of a novel component of the
      T9SS. Knowledge of how T9SS operates will contribute to our understanding of
      protein secretion as part of host-microbiome interactions by dysbiotic members of
      the human oral cavity.

PMID- 27883040
TI  - Effects of MeJA on Arabidopsis metabolome under endogenous JA deficiency.
AB  - Jasmonates (JAs) play important roles in plant growth, development and defense.
      Comprehensive metabolomics profiling of plants under JA treatment provides
      insights into the interaction and regulation network of plant hormones. Here we
      applied high resolution mass spectrometry based metabolomics approach on
      Arabidopsis wild type and JA synthesis deficiency mutant opr3. The effects of
      exogenous MeJA treatment on the metabolites of opr3 were investigated. More than
      10000 ion signals were detected and more than 2000 signals showed significant
      variation in different genotypes and treatment groups. Multivariate statistic
      analyses (PCA and PLS-DA) were performed and a differential compound library
      containing 174 metabolites with high resolution precursor ion-product ions pairs
      was obtained. Classification and pathway analysis of 109 identified compounds in
      this library showed that glucosinolates and tryptophan metabolism, amino acids
      and small peptides metabolism, lipid metabolism, especially fatty acyls
      metabolism, were impacted by endogenous JA deficiency and exogenous MeJA
      treatment. These results were further verified by quantitative reverse
      transcription PCR (RT-qPCR) analysis of 21 related genes involved in the
      metabolism of glucosinolates, tryptophan and alpha-linolenic acid pathways. The
      results would greatly enhance our understanding of the biological functions of
      JA.

PMID- 27883041
TI  - Interaction between beta-hexachlorocyclohexane and ADIPOQ genotypes contributes
      to the risk of type 2 diabetes mellitus in East Chinese adults.
AB  - Growing evidence links environmental exposure to hexachlorocyclohexanes (HCHs) to
      the risk of type 2 diabetes mellitus (T2DM), and ADIPOQ that encodes adiponectin
      is considered as an important gene for T2DM. However, the role of ADIPOQ-HCH
      interaction on T2DM risk remains unclear. Thus, a paired case-control study was
      conducted in an East Chinese community. A total of 1446 subjects, including 723
      cases and 723 controls matched on age, gender and residence, were enrolled, and 4
      types of HCH isomers were measured in serum samples using GC-MS/MS. Additionally,
      4 candidate ADIPOQ SNPs (rs182052, rs266729, rs6810075, and rs16861194) were
      genotyped by TaqMan assay, and plasma adiponectin was measured using ELISA. No
      associations between 4 SNPs and T2DM risk were found, but T2DM risk significantly
      increased with serum levels of beta-HCH (P < 0.001). Furthermore, the synergistic
      interaction between beta-HCH and rs182052 significantly increased T2DM risk (OR I
      additive model = 2.20, OR I-recessive model = 2.13). Additionally, individuals
      carrying only rs182052 (A allele) with high levels of beta-HCH had significant
      reduction in adiponectin levels (P = 0.016). These results indicate that the
      interaction between rs182052 and beta-HCH might increase the risk of T2DM by
      jointly decreasing the adiponectin level and potentially trigger T2DM
      development.

PMID- 27883043
TI  - Acceleration toward polarization singularity inspired by relativistic E*B drift.
AB  - The relativistic trajectory of a charged particle driven by the Lorentz force is
      different from the classical one, by velocity-dependent relativistic acceleration
      term. Here we show that the evolution of optical polarization states near the
      polarization singularity can be described in analogy to the relativistic dynamics
      of charged particles. A phase transition in parity-time symmetric potentials is
      then interpreted in terms of the competition between electric and magnetic
      'pseudo'-fields applied to polarization states. Based on this Lorentz pseudo
      force representation, we reveal that zero Lorentz pseudo-force is the origin of
      recently reported strong polarization convergence to the singular state at the
      exceptional point. We also demonstrate the deterministic design of achiral and
      directional eigenstates at the exceptional point, allowing an anomalous linear
      polarizer which operates orthogonal to forward and backward waves. Our results
      linking parity-time symmetry and relativistic electrodynamics show that previous
      PT-symmetric potentials for the polarization singularity with a chiral eigenstate
      are the subset of optical potentials for the E*B "polarization" drift.

PMID- 27883044
TI  - Predicting the location of the hip joint centres, impact of age group and sex.
AB  - Clinical gait analysis incorporating three-dimensional motion analysis plays a
      key role in planning surgical treatments in people with gait disability. The
      position of the Hip Joint Centre (HJC) within the pelvis is thus critical to
      ensure accurate data interpretation. The position of the HJC is determined from
      regression equations based on anthropometric measurements derived from relatively
      small datasets. Current equations do not take sex or age into account, even
      though pelvis shape is known to differ between sex, and gait analysis is
      performed in populations with wide range of age. Three dimensional images of 157
      deceased individuals (37 children, 120 skeletally matured) were collected with
      computed tomography. The location of the HJC within the pelvis was determined and
      regression equations to locate the HJC were developed using various
      anthropometrics predictors. We determined if accuracy improved when age and sex
      were introduced as variables. Statistical analysis did not support
      differentiating the equations according to sex. We found that age only modestly
      improved accuracy. We propose a range of new regression equations, derived from
      the largest dataset collected for this purpose to date.

PMID- 27883045
TI  - Acidic mammalian chitinase is a proteases-resistant glycosidase in mouse
      digestive system.
AB  - Chitinases are enzymes that hydrolyze chitin, a polymer of beta-1, 4-linked N
      acetyl-D-glucosamine (GlcNAc). Chitin has long been considered as a source of
      dietary fiber that is not digested in the mammalian digestive system. Here, we
      provide evidence that acidic mammalian chitinase (AMCase) can function as a major
      digestive enzyme that constitutively degrades chitin substrates and produces
      (GlcNAc)2 fragments in the mouse gastrointestinal environment. AMCase was
      resistant to endogenous pepsin C digestion and remained active in the mouse
      stomach extract at pH 2.0. The AMCase mRNA levels were much higher than those of
      four major gastric proteins and two housekeeping genes and comparable to the
      level of pepsinogen C in the mouse stomach tissues. Furthermore, AMCase was
      expressed in the gastric pepsinogen-synthesizing chief cells. The enzyme was also
      stable and active in the presence of trypsin and chymotrypsin at pH 7.6, where
      pepsin C was completely degraded. Mouse AMCase degraded polymeric colloidal and
      crystalline chitin substrates in the gastrointestinal environments in presence of
      the proteolytic enzymes. Thus, AMCase can function as a protease-resistant major
      glycosidase under the conditions of stomach and intestine and degrade chitin
      substrates to produce (GlcNAc)2, a source of carbon, nitrogen and energy.

PMID- 27883046
TI  - Holding-on: co-evolution between infant carrying and grasping behaviour in
      strepsirrhines.
AB  - The origin and evolution of manual grasping remain poorly understood. The ability
      to cling requires important grasping abilities and is essential to survive in
      species where the young are carried in the fur. A previous study has suggested
      that this behaviour could be a pre-adaptation for the evolution of fine
      manipulative skills. In this study we tested the co-evolution between infant
      carrying in the fur and manual grasping abilities in the context of food
      manipulation. As strepsirrhines vary in the way infants are carried (mouth vs.
      fur), they are an excellent model to test this hypothesis. Data on food
      manipulation behaviour were collected for 21 species of strepsirrhines. Our
      results show that fur-carrying species exhibited significantly more frequent
      manual grasping of food items. This study clearly illustrates the potential novel
      insights that a behaviour (infant carrying) that has previously been largely
      ignored in the discussion of the evolution of primate manipulation can bring.

PMID- 27883047
TI  - Highly expressed ribosomal protein L34 indicates poor prognosis in osteosarcoma
      and its knockdown suppresses osteosarcoma proliferation probably through
      translational control.
AB  - Osteosarcoma has devastating health implications on children and adolescents.
      However, due to its low incidence and high tumor heterogeneity, it is hard to
      achieve any further improvements in therapy and overall survival. Ribosomal
      protein L34 (RPL34) has been increasingly recognized to promote the proliferation
      of malignant cells, but its role in osteosarcoma has not been investigated. In
      this study, real-time quantitative PCR (RT-qPCR) and immunohistochemistry
      revealed that RPL34 was highly expressed in osteosarcoma tissues when compared to
      adjacent tissues and normal bone tissues. Survival analysis showed that high
      expression of RPL34 predicted a poor prognosis for osteosarcoma patients.
      Knockdown of RPL34 in Saos-2 cells via lentivirus-mediated small interfering RNA
      (siRNA) significantly inhibited cell proliferation, induced cell apoptosis and
      G2/M phase arrest. Moreover, screening of transcription factors using University
      of California Santa Cruz (UCSC) Genome Browser, protein-protein interaction (PPI)
      network analysis, Gene Ontology (GO) and pathway enrichment analysis revealed
      that MYC participates in the transcriptional regulation of RPL34, which interacts
      with the subunits of eukaryotic translation initiation factor 3 (eIF3) and
      probably involves the translational control of growth-promoting proteins. Our
      findings suggest that RPL34 plays an important role in the proliferation of
      osteosarcoma cells.

PMID- 27883050
TI  - Reduction of randomness in seismic noise as a short-term precursor to a volcanic
      eruption.
AB  - Ambient seismic noise is characterized by randomness incurred by the random
      position and strength of the noise sources as well as the heterogeneous
      properties of the medium through which it propagates. Here we use ambient noise
      data recorded prior to the 1996 Gjalp eruption in Iceland in order to show that a
      reduction of noise randomness can be a clear short-term precursor to volcanic
      activity. The eruption was preceded on 29 September 1996 by a Mw ~5.6 earthquake
      that occurred in the caldera rim of the Bardarbunga volcano. A significant
      reduction of randomness started occurring 8 days before the earthquake and 10
      days before the onset of the eruption. This reduction was observed even at
      stations more than 100 km away from the eruption site. Randomness increased to
      its previous levels 160 minutes after the Bardarbunga earthquake, during which
      time aftershocks migrated from the Bardarbunga caldera to a site near the Gjalp
      eruption fissure. We attribute this precursory reduction of randomness to the
      lack of higher frequencies (>1 Hz) in the noise wavefield caused by high
      absorption losses as hot magma ascended in the upper crust.

PMID- 27883049
TI  - mQC: A Heuristic Quality-Control Metric for High-Throughput Drug Combination
      Screening.
AB  - Quality control (QC) metrics are critical in high throughput screening (HTS)
      platforms to ensure reliability and confidence in assay data and downstream
      analyses. Most reported HTS QC metrics are designed for plate level or single
      well level analysis. With the advent of high throughput combination screening
      there is a need for QC metrics that quantify the quality of combination response
      matrices. We introduce a predictive, interpretable, matrix-level QC metric, mQC,
      based on a mix of data-derived and heuristic features. mQC accurately reproduces
      the expert assessment of combination response quality and correctly identifies
      unreliable response matrices that can lead to erroneous or misleading
      characterization of synergy. When combined with the plate-level QC metric, Z',
      mQC provides a more appropriate determination of the quality of a drug
      combination screen. Retrospective analysis on a number of completed combination
      screens further shows that mQC is able to identify problematic screens whereas
      plate-level QC was not able to. In conclusion, our data indicates that mQC is a
      reliable QC filter that can be used to identify problematic drug combinations
      matrices and prevent further analysis on erroneously active combinations as well
      as for troubleshooting failed screens. The R source code of mQC is available at
      http://matrix.ncats.nih.gov/mQC.

PMID- 27883048
TI  - Proteomic profile of the Bradysia odoriphaga in response to the microbial
      secondary metabolite benzothiazole.
AB  - Benzothiazole, a microbial secondary metabolite, has been demonstrated to possess
      fumigant activity against Sclerotinia sclerotiorum, Ditylenchus destructor and
      Bradysia odoriphaga. However, to facilitate the development of novel microbial
      pesticides, the mode of action of benzothiazole needs to be elucidated. Here, we
      employed iTRAQ-based quantitative proteomics analysis to investigate the effects
      of benzothiazole on the proteomic expression of B. odoriphaga. In response to
      benzothiazole, 92 of 863 identified proteins in B. odoriphaga exhibited altered
      levels of expression, among which 14 proteins were related to the action
      mechanism of benzothiazole, 11 proteins were involved in stress responses, and 67
      proteins were associated with the adaptation of B. odoriphaga to benzothiazole.
      Further bioinformatics analysis indicated that the reduction in energy
      metabolism, inhibition of the detoxification process and interference with DNA
      and RNA synthesis were potentially associated with the mode of action of
      benzothiazole. The myosin heavy chain, succinyl-CoA synthetase and Ca+
      transporting ATPase proteins may be related to the stress response. Increased
      expression of proteins involved in carbohydrate metabolism, energy production and
      conversion pathways was responsible for the adaptive response of B. odoriphaga.
      The results of this study provide novel insight into the molecular mechanisms of
      benzothiazole at a large-scale translation level and will facilitate the
      elucidation of the mechanism of action of benzothiazole.

PMID- 27883052
TI  - Electrical Switching in Semiconductor-Metal Self-Assembled VO2 Disordered
      Metamaterial Coatings.
AB  - As a strongly correlated metal oxide, VO2 inspires several highly technological
      applications. The challenging reliable wafer-scale synthesis of high quality
      polycrystalline VO2 coatings is demonstrated on 4" Si taking advantage of the
      oxidative sintering of chemically vapor deposited VO2 films. This approach
      results in films with a semiconductor-metal transition (SMT) quality approaching
      that of the epitaxial counterpart. SMT occurs with an abrupt electrical
      resistivity change exceeding three orders of magnitude with a narrow hysteresis
      width. Spatially resolved infrared and Raman analyses evidence the self-assembly
      of VO2 disordered metamaterial, compresing monoclinic (M1 and M2) and rutile (R)
      domains, at the transition temperature region. The M2 mediation of the M1-R
      transition is spatially confined and related to the localized strain
      stabilization of the M2 phase. The presence of the M2 phase is supposed to play a
      role as a minor semiconducting phase far above the SMT temperature. In terms of
      application, we show that the VO2 disordered self-assembly of M and R phases is
      highly stable and can be thermally triggered with high precision using short
      heating or cooling pulses with adjusted strengths. Such a control enables an
      accurate and tunable thermal control of the electrical switching.

PMID- 27883053
TI  - Measuring intratumor heterogeneity by network entropy using RNA-seq data.
AB  - Intratumor heterogeneity (ITH) is observed at different stages of tumor
      progression, metastasis and reouccurence, which can be important for clinical
      applications. We used RNA-sequencing data from tumor samples, and measured the
      level of ITH in terms of biological network states. To model complex
      relationships among genes, we used a protein interaction network to consider gene
      gene dependency. ITH was measured by using an entropy-based distance metric
      between two networks, nJSD, with Jensen-Shannon Divergence (JSD). With nJSD, we
      defined transcriptome-based ITH (tITH). The effectiveness of tITH was extensively
      tested for the issues related with ITH using real biological data sets. Human
      cancer cell line data and single-cell sequencing data were investigated to verify
      our approach. Then, we analyzed TCGA pan-cancer 6,320 patients. Our result was in
      agreement with widely used genome-based ITH inference methods, while showed
      better performance at survival analysis. Analysis of mouse clonal evolution data
      further confirmed that our transcriptome-based ITH was consistent with genetic
      heterogeneity at different clonal evolution stages. Additionally, we found that
      cell cycle related pathways have significant contribution to increasing
      heterogeneity on the network during clonal evolution. We believe that the
      proposed transcriptome-based ITH is useful to characterize heterogeneity of a
      tumor sample at RNA level.

PMID- 27883054
TI  - Castable Bulk Metallic Glass Strain Wave Gears: Towards Decreasing the Cost of
      High-Performance Robotics.
AB  - The use of bulk metallic glasses (BMGs) as the flexspline in strain wave gears
      (SWGs), also known as harmonic drives, is presented. SWGs are unique, ultra
      precision gearboxes that function through the elastic flexing of a thin-walled
      cup, called a flexspline. The current research demonstrates that BMGs can be cast
      at extremely low cost relative to machining and can be implemented into SWGs as
      an alternative to steel. This approach may significantly reduce the cost of SWGs,
      enabling lower-cost robotics. The attractive properties of BMGs, such as
      hardness, elastic limit and yield strength, may also be suitable for extreme
      environment applications in spacecraft.

PMID- 27883051
TI  - Lipid Coated Microbubbles and Low Intensity Pulsed Ultrasound Enhance
      Chondrogenesis of Human Mesenchymal Stem Cells in 3D Printed Scaffolds.
AB  - Lipid-coated microbubbles are used to enhance ultrasound imaging and drug
      delivery. Here we apply these microbubbles along with low intensity pulsed
      ultrasound (LIPUS) for the first time to enhance proliferation and chondrogenic
      differentiation of human mesenchymal stem cells (hMSCs) in a 3D printed poly
      (ethylene glycol)-diacrylate (PEG-DA) hydrogel scaffold. The hMSC proliferation
      increased up to 40% after 5 days of culture in the presence of 0.5% (v/v)
      microbubbles and LIPUS in contrast to 18% with LIPUS alone. We systematically
      varied the acoustic excitation parameters-excitation intensity, frequency and
      duty cycle-to find 30 mW/cm2, 1.5 MHz and 20% duty cycle to be optimal for hMSC
      proliferation. A 3-week chondrogenic differentiation results demonstrated that
      combining LIPUS with microbubbles enhanced glycosaminoglycan (GAG) production by
      17% (5% with LIPUS alone), and type II collagen production by 78% (44% by LIPUS
      alone). Therefore, integrating LIPUS and microbubbles appears to be a promising
      strategy for enhanced hMSC growth and chondrogenic differentiation, which are
      critical components for cartilage regeneration. The results offer possibilities
      of novel applications of microbubbles, already clinically approved for contrast
      enhanced ultrasound imaging, in tissue engineering.

PMID- 27883056
TI  - Authenticity screening of stained glass windows using optical spectroscopy.
AB  - Civilized societies should safeguard their heritage as it plays an important role
      in community building. Moreover, past technologies often inspire new technology.
      Authenticity is besides conservation and restoration a key aspect in preserving
      our past, for example in museums when exposing showpieces. The classification of
      being authentic relies on an interdisciplinary approach integrating art
      historical and archaeological research complemented with applied research. In
      recent decades analytical dating tools are based on determining the raw materials
      used. However, the traditional applied non-portable, chemical techniques are
      destructive and time-consuming. Since museums oftentimes only consent to research
      actions which are completely non-destructive, optical spectroscopy might offer a
      solution. As a case-study we apply this technique on two stained glass panels for
      which the 14th century dating is nowadays questioned. With this research we were
      able to identify how simultaneous mapping of spectral signatures measured with a
      low cost optical spectrum analyser unveils information regarding the production
      period. The significance of this research extends beyond the re-dating of these
      panels to the 19th century as it provides an instant tool enabling immediate
      answering authenticity questions during the conservation process of stained
      glass, thereby providing the necessary data for solving deontological questions
      about heritage preservation.

PMID- 27883061
TI  - Unravelling the dynamical origin of below- and near-threshold harmonic generation
      of H2+ in an intense NIR laser field.
AB  - Recently, the study of near- and below- threshold regime harmonics as a potential
      source of intense coherent vacuum-ultraviolet radiation has received considerable
      attention. However, the dynamical origin of these lower harmonics, particularly
      for the molecular systems, is less understood and largely unexplored. Here we
      perform the first fully ab initio and high precision 3D quantum study of the
      below- and near-threshold harmonic generation of molecules in an intense 800-nm
      near-infrared (NIR) laser field. Combining with a synchrosqueezing transform of
      the quantum time-frequency spectrum and an extended semiclassical analysis, we
      explore in-depth the roles of various quantum trajectories, including short- and
      long trajectories, multiphoton trajectories, resonance-enhanced trajectories, and
      multiple rescattering trajectories of the below- and near- threshold harmonic
      generation processes. Our results shed new light on the dynamical origin of the
      below- and near-threshold harmonic generation and various quantum trajectories
      for diatomic molecules for the first time.

PMID- 27883055
TI  - GapmeR cellular internalization by macropinocytosis induces sequence-specific
      gene silencing in human primary T-cells.
AB  - Post-transcriptional gene silencing holds great promise in discovery research for
      addressing intricate biological questions and as therapeutics. While various gene
      silencing approaches, such as siRNA and CRISPR-Cas9 techniques, are available,
      these cannot be effectively applied to "hard-to-transfect" primary T-lymphocytes.
      The locked nucleic acid-conjugated chimeric antisense oligonucleotide, called
      "GapmeR", is an emerging new class of gene silencing molecule. Here, we show that
      GapmeR internalizes into human primary T-cells through macropinocytosis.
      Internalized GapmeR molecules can associate with SNX5-positive macropinosomes in
      T-cells, as detected by super-resolution microscopy. Utilizing the intrinsic self
      internalizing capability of GapmeR, we demonstrate significant and specific
      depletion (>70%) of the expression of 5 different endogenous proteins with
      varying molecular weights (18 kDa Stathmin, 80 kDa PKCepsilon, 180 kDa CD11a, 220
      kDa Talin1 and 450 kDa CG-NAP/AKAP450) in human primary and cultured T-cells.
      Further functional analysis confirms CG-NAP and Stathmin as regulators of T-cell
      motility. Thus, in addition to screening, identifying or verifying critical roles
      of various proteins in T-cell functioning, this study provides novel
      opportunities to silence individual or multiple genes in a subset of purified
      human primary T-cells that would be exploited as future therapeutics.

PMID- 27883062
TI  - Genome-wide transcriptome analysis revealed organelle specific responses to
      temperature variations in algae.
AB  - Temperature is a critical environmental factor that affects microalgal growth.
      However, microalgal coping mechanisms for temperature variations are unclear.
      Here, we determined changes in transcriptome, total carbohydrate, total fatty
      acid methyl ester, and fatty acid composition of Tetraselmis sp. KCTC12432BP, a
      strain with a broad temperature tolerance range, to elucidate the tolerance
      mechanisms in response to large temperature variations. Owing to unavailability
      of genome sequence information, de novo transcriptome assembly coupled with BLAST
      analysis was performed using strand specific RNA-seq data. This resulted in
      26,245 protein-coding transcripts, of which 83.7% could be annotated to putative
      functions. We identified more than 681 genes differentially expressed, suggesting
      an organelle-specific response to temperature variation. Among these, the genes
      related to the photosynthetic electron transfer chain, which are localized in the
      plastid thylakoid membrane, were upregulated at low temperature. However, the
      transcripts related to the electron transport chain and biosynthesis of
      phosphatidylethanolamine localized in mitochondria were upregulated at high
      temperature. These results show that the low energy uptake by repressed
      photosynthesis under low and high temperature conditions is compensated by
      different mechanisms, including photosystem I and mitochondrial oxidative
      phosphorylation, respectively. This study illustrates that microalgae tolerate
      different temperature conditions through organelle specific mechanisms.

PMID- 27883063
TI  - On-demand Hydrogen Production from Organosilanes at Ambient Temperature Using
      Heterogeneous Gold Catalysts.
AB  - An environmentally friendly ("green"), H2-generation system was developed that
      involved hydrolytic oxidation of inexpensive organosilanes as hydrogen storage
      materials with newly developed heterogeneous gold nanoparticle catalysts. The
      gold catalyst functioned well at ambient temperature under aerobic conditions,
      providing efficient production of pure H2. The newly developed size-selective
      gold nanoparticle catalysts could be separated easily from the reaction mixture
      containing organosilanes, allowing an on/off-switchable H2-production by the
      introduction and removal of the catalyst. This is the first report of an on/off
      switchable H2-production system employing hydrolytic oxidation of inexpensive
      organosilanes without requiring additional energy.

PMID- 27883066
TI  - Meteotsunamis in the Laurentian Great Lakes.
AB  - The generation mechanism of meteotsunamis, which are meteorologically induced
      water waves with spatial/temporal characteristics and behavior similar to seismic
      tsunamis, is poorly understood. We quantify meteotsunamis in terms of
      seasonality, causes, and occurrence frequency through the analysis of long-term
      water level records in the Laurentian Great Lakes. The majority of the observed
      meteotsunamis happen from late-spring to mid-summer and are associated primarily
      with convective storms. Meteotsunami events of potentially dangerous magnitude
      (height > 0.3 m) occur an average of 106 times per year throughout the region.
      These results reveal that meteotsunamis are much more frequent than follow from
      historic anecdotal reports. Future climate scenarios over the United States show
      a likely increase in the number of days favorable to severe convective storm
      formation over the Great Lakes, particularly in the spring season. This would
      suggest that the convectively associated meteotsunamis in these regions may
      experience an increase in occurrence frequency or a temporal shift in occurrence
      to earlier in the warm season. To date, meteotsunamis in the area of the Great
      Lakes have been an overlooked hazard.

PMID- 27883060
TI  - Environmental Intervention as a Therapy for Adverse Programming by Ancestral
      Stress.
AB  - Ancestral stress can program stress sensitivity and health trajectories across
      multiple generations. While ancestral stress is uncontrollable to the filial
      generations, it is critical to identify therapies that overcome transgenerational
      programming. Here we report that prenatal stress in rats generates a
      transgenerationally heritable endocrine and epigenetic footprint and elevated
      stress sensitivity which can be alleviated by beneficial experiences in later
      life. Ancestral stress led to downregulated glucocorticoid receptor and
      prefrontal cortex neuronal densities along with precocious development of anxiety
      like behaviours. Environmental enrichment (EE) during adolescence mitigated
      endocrine and neuronal markers of stress and improved miR-182 expression linked
      to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) regulation
      in stressed lineages. Thus, EE may serve as a powerful intervention for adverse
      transgenerational programming through microRNA-mediated regulation of BDNF and NT
      3 pathways. The identification of microRNAs that mediate the actions of EE
      highlights new therapeutic strategies for mental health conditions and
      psychiatric disease.

PMID- 27883065
TI  - Cycles of circadian illuminance are sufficient to entrain and maintain circadian
      locomotor rhythms in Drosophila.
AB  - Light at night disrupts the circadian clock and causes serious health problems in
      the modern world. Here, we show that newly developed four-package light-emitting
      diodes (LEDs) can provide harmless lighting at night. To quantify the effects of
      light on the circadian clock, we employed the concept of circadian illuminance
      (CIL). CIL represents the amount of light weighted toward the wavelengths to
      which the circadian clock is most sensitive, whereas visual illuminance (VIL)
      represents the total amount of visible light. Exposure to 12 h:12 h cycles of
      white LED light with high and low CIL values but a constant VIL value (conditions
      hereafter referred to as CH/CL) can entrain behavioral and molecular circadian
      rhythms in flies. Moreover, flies re-entrain to phase shift in the CH/CL cycle.
      Core-clock proteins are required for the rhythmic behaviors seen with this LED
      lighting scheme. Taken together, this study provides a guide for designing
      healthful white LED lights for use at night, and proposes the use of the CIL
      value for estimating the harmful effects of any light source on organismal
      health.

PMID- 27883057
TI  - The Warburg Effect Mediator Pyruvate Kinase M2 Expression and Regulation in the
      Retina.
AB  - The tumor form of pyruvate kinase M2 (PKM2) undergoes tyrosine phosphorylation
      and gives rise to the Warburg effect. The Warburg effect defines a pro-oncogenic
      metabolism switch such that cancer cells take up more glucose than normal tissue
      and favor incomplete oxidation of glucose, even in the presence of oxygen.
      Retinal photoreceptors are highly metabolic and their energy consumption is
      equivalent to that of a multiplying tumor cell. In the present study, we found
      that PKM2 is the predominant isoform in both rod- and cone-dominant retina, and
      that it undergoes a light-dependent tyrosine phosphorylation. We also discovered
      that PKM2 phosphorylation is signaled through photobleaching of rhodopsin. Our
      findings suggest that phosphoinositide 3-kinase activation promotes PKM2
      phosphorylation. Light and tyrosine phosphorylation appear to regulate PKM2 to
      provide a metabolic advantage to photoreceptor cells, thereby promoting cell
      survival.

PMID- 27883067
TI  - All-optical THz wave switching based on CH3NH3PbI3 perovskites.
AB  - Hybrid structures of silicon with organic-inorganic perovskites are proposed for
      optically controllable switching of terahertz (THz) waves over a broad spectral
      range from 0.2 to 2THz. A 532-nm external laser was utilized to generate
      photoexcited free carriers at the devices and consequentially to control the
      terahertz amplitude modulation, obtaining a depth of up to 68% at a laser
      irradiance of 1.5 W/cm2. In addition, we compared the performances from three
      types of perovskite devices fabricated via different solution processing methods
      and suggested a stable and highly efficient THz switch based on a one-step
      processing. By this we demonstrated the possibility of perovskites as THz wave
      switching devices in addition to photovoltaics.

PMID- 27883058
TI  - Role of ectonucleotide pyrophosphatase/phosphodiesterase 2 in the midline axis
      formation of zebrafish.
AB  - Lysophosphatidic acid (LPA) is a unique bioactive lysophospholipid that induces
      pleiotropic effects in various cell types and organisms by acting on its specific
      receptors. LPA is mainly synthetised extracellularly by the ectonucleotide
      pyrophosphatase/phosphodiesterase 2/autotaxin (enpp2). Altered LPA signalling is
      associated with embryonic abnormalities, suggesting critical roles for LPA during
      development. However, the role of LPA signalling during early embryogenesis is
      not well established. We demonstrate that enpp2/LPA signalling in the early
      zebrafish embryo results in altered axis and midline formation, defects in left
      right (L-R) patterning, ciliogenesis of the Kupffer's vesicle (KV), through the
      modulation of cell migration during gastrulation in a lpar1-3 Rho/ROCK-dependant
      manner. Overall, this study demonstrates an essential role of enpp2/LPA
      signalling during early embryogenesis.

PMID- 27883068
TI  - "Cerebellar contribution to visuo-attentional alpha rhythm: insights from
      weightlessness".
AB  - Human brain adaptation in weightlessness follows the necessity to reshape the
      dynamic integration of the neural information acquired in the new environment.
      This basic aspect was here studied by the electroencephalogram (EEG) dynamics
      where oscillatory modulations were measured during a visuo-attentional state
      preceding a visuo-motor docking task. Astronauts in microgravity conducted the
      experiment in free-floating aboard the International Space Station, before the
      space flight and afterwards. We observed stronger power decrease (~ERD: event
      related desynchronization) of the ~10 Hz oscillation from the occipital-parietal
      (alpha ERD) to the central areas (mu ERD). Inverse source modelling of the
      stronger alpha ERD revealed a shift from the posterior cingulate cortex (BA31,
      from the default mode network) on Earth to the precentral cortex (BA4, primary
      motor cortex) in weightlessness. We also observed significant contribution of the
      vestibular network (BA40, BA32, and BA39) and cerebellum (lobule V, VI). We
      suggest that due to the high demands for the continuous readjustment of an
      appropriate body posture in free-floating, this visuo-attentional state required
      more contribution from the motor cortex. The cerebellum and the vestibular
      network involvement in weightlessness might support the correction signals
      processing necessary for postural stabilization, and the increased demand to
      integrate incongruent vestibular information.

PMID- 27883064
TI  - The microRNA toolkit of insects.
AB  - Is there a correlation between miRNA diversity and levels of organismic
      complexity? Exhibiting extraordinary levels of morphological and developmental
      complexity, insects are the most diverse animal class on earth. Their
      evolutionary success was in particular shaped by the innovation of holometabolan
      metamorphosis in endopterygotes. Previously, miRNA evolution had been linked to
      morphological complexity, but astonishing variation in the currently available
      miRNA complements of insects made this link unclear. To address this issue, we
      sequenced the miRNA complement of the hemimetabolan Blattella germanica and
      reannotated that of two other hemimetabolan species, Locusta migratoria and
      Acyrthosiphon pisum, and of four holometabolan species, Apis mellifera, Tribolium
      castaneum, Bombyx mori and Drosophila melanogaster. Our analyses show that the
      variation of insect miRNAs is an artefact mainly resulting from poor sampling and
      inaccurate miRNA annotation, and that insects share a conserved microRNA toolkit
      of 65 families exhibiting very low variation. For example, the evolutionary shift
      toward a complete metamorphosis was accompanied only by the acquisition of three
      and the loss of one miRNA families.

PMID- 27883059
TI  - Hepatic SATB1 induces paracrine activation of hepatic stellate cells and is
      upregulated by HBx.
AB  - Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver
      diseases, but its involvement in hepatic fibrogenesis remains unclear. Special AT
      rich binding protein 1 (SATB1) has been implicated in reprogramming chromatin
      organization and transcription profiles in many cancers and non-cancer-related
      conditions. We found that hepatic SATB1 expression was significantly up-regulated
      in fibrotic tissues from chronic hepatitis B virus (HBV)-infected patients and
      HBV transgenic (HBV-Tg) mouse model. Knockdown of SATB1 in the liver
      significantly alleviated CCl4-induced fibrosis in HBV-Tg mouse model. Moreover,
      we suggested HBV encoded x protein (HBx) induced SATB1 expression through
      activation of JNK and ERK pathways. Enforced expression of SATB1 in hepatocytes
      promoted the activation and proliferation of hepatic stellate cells (HSCs) by
      secretion of connective tissue growth factor (CTGF), Interleukin-6 (IL-6) and
      platelet derived growth factor-A (PDGF-AA). Our findings demonstrated that HBx
      upregulated hepatic SATB1 which exerted pro-fibrotic effects by paracrine
      activation of stellate cells in HBV-related fibrosis.

PMID- 27883070
TI  - pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for
      Cancer Drug Delivery.
AB  - Multifunctional nanocarriers harbouring specific targeting moieties and with pH
      responsive properties offer great potential for targeted cancer therapy. Several
      synthetic drug carriers have been studied extensively as drug delivery systems
      but not much information is available on the application of virus-like
      nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the
      development of pH-responsive VLNPs, based on truncated hepatitis B virus core
      antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was
      conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg
      nanoparticles to increase the specificity and efficacy of the drug delivery
      system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic
      acid (PAA) demonstrated a sustained drug release profile in vitro under tumour
      tissue conditions in a controlled manner and improved the uptake of DOX in
      colorectal cancer cells, leading to enhanced antitumour effects. This study
      demonstrated that DOX-PAA can be packaged into VLNPs without any modification of
      the DOX molecules, preserving the pharmacological activity of the loaded DOX. The
      nanoglue can easily be used to display a tumour-targeting molecule on the
      exterior surface of VLNPs and can bypass the laborious and time-consuming genetic
      engineering approaches.

PMID- 27883069
TI  - Quality of Life and Cost-Effectiveness of Radiofrequency Ablation versus Open
      Surgery for Benign Thyroid Nodules: a retrospective cohort study.
AB  - This study is to compare the health-related quality of life (HRQoL) and cost
      effectiveness of radiofrequency ablation (RFA) and open thyroidectomy (OT) for
      benign thyroid nodules (BTNs) treatment. HRQoL and utility were assessed for 404
      BTN patients immediately before treatments (RFA:OT = 137:267) and at 6-month
      visit. A cost-effectiveness analysis was performed from societal perspective in
      the China context. Resource use (hospitalization, sick leaves) was collected. We
      used the net monetary benefit approach and computed cost-effectiveness
      acceptability curves for RFA and OT. Sensitivity analyses of costs of RFA were
      performed. At 6-month visit, patients treated with RFA had significantly better
      HRQoL than patients treated with OT on general health (68.5 versus 66.7, P =
      0.029), vitality (71.3 versus 67.5, P < 0.001) and mental health (80.9 versus
      79.3, P = 0.038). RFA was more effective than OT in terms of quality-adjusted
      life-years (QALYs; 0.01QALY/patient) but more expensive (US$823/patient). The
      probability that RFA would be cost effective at a US$50,000/QALY threshold was
      15.5% in China, and it would be increased to 88.4% when price of the RFA device
      was lowered by 30%. RFA exhibited a significant improvement of HRQoL relative to
      OT, but is unlikely to be cost effective at its current price in short time.

PMID- 27883073
TI  - The preparation and characterization of a novel sphingan WL from marine
      Sphingomonas sp. WG.
AB  - Sphingans, a group of structurally closely related bacterial exopolysaccharides
      produced by members of the genus Sphingomonas, can be applied in a variety of
      industries such as food, cement, and personal care applications due to their high
      viscosity. A high sphingan-producing-bacterium, Sphingomonas sp. WG can secret
      large quantity of sphingan designated as WL. To enhance the production of WL, a
      three-stage control strategy was applied and the highest WL production can reach
      33.3 g/L. The rheological analysis showed that the aqueous solution of WL had
      high viscosity, typical shearing-thinning behavior and great stability to high
      temperature, a wide range of pH (1 to 14), and high salinity. WL was composed
      principally of carbohydrate with 6.52% O-acyl groups. The carbohydrate portion of
      WL contained about 13% glucuronic acid and some neutral sugars including mannose,
      glucose and rhamnose in the molar ratio of 1:2.28:2.12. Partial acid hydrolysis
      of WL produced a new oligosaccharide WL-1. Structural resolution revealed that WL
      1 consisted of alpha-L-Rha-(1->4)-beta-L-Rha-(1->4)-beta-D-Glc-(1->3)-alpha-D-Glc
      with beta-D-Man substituent at the third glucose residue and carboxyl and O-acyl
      groups. These findings will broaden the applications of this novel sphingan in
      food, ink, oil and other industries.

PMID- 27883077
TI  - TGF beta receptor II interacting protein-1, an intracellular protein has an
      extracellular role as a modulator of matrix mineralization.
AB  - Transforming growth factor beta receptor II interacting protein 1 (TRIP-1), a
      predominantly intracellular protein is localized in the ECM of bone. TRIP-1 lacks
      a signal peptide, therefore, in this study, we provide evidence that
      intracellular TRIP-1 can be packaged and exported to the ECM via exosomes.
      Overexpression of TRIP-1 in MC3T3-E1 cells resulted in increased matrix
      mineralization during differentiation and knockdown resulted in reduced effects.
      In vivo function of TRIP-1 was studied by an implantation assay performed using
      TRIP-1 overexpressing and knockdown cells cultured in a 3-dimmensional scaffold.
      After 4 weeks, the subcutaneous tissues from TRIP-1 overexpressing cells showed
      higher calcium and phosphate deposits, arranged collagen fibrils and increased
      expression of Runx2 and alkaline phosphatase. Nucleation studies on demineralized
      and deproteinized dentin wafer is a powerful tool to determine the functional
      role of noncollagenous proteins in matrix mineralization. Using this system, we
      provide evidence that TRIP-1 binds to Type-I collagen and can promote
      mineralization. Surface plasmon resonance analysis demonstrated that TRIP-1 binds
      to collagen with KD = 48 MUM. SEM and TEM analysis showed that TRIP-1 promoted
      the nucleation and growth of calcium phosphate mineral aggregates. Taken
      together, we provide mechanistic insights of this intracellular protein in matrix
      mineralization.

PMID- 27883072
TI  - Non-RVD mutations that enhance the dynamics of the TAL repeat array along the
      superhelical axis improve TALEN genome editing efficacy.
AB  - Transcription activator-like effector (TALE) nuclease (TALEN) is widely used as a
      tool in genome editing. The DNA binding part of TALEN consists of a tandem array
      of TAL-repeats that form a right-handed superhelix. Each TAL-repeat recognises a
      specific base by the repeat variable diresidue (RVD) at positions 12 and 13.
      TALEN comprising the TAL-repeats with periodic mutations to residues at positions
      4 and 32 (non-RVD sites) in each repeat (VT-TALE) exhibits increased efficacy in
      genome editing compared with a counterpart without the mutations (CT-TALE). The
      molecular basis for the elevated efficacy is unknown. In this report, comparison
      of the physicochemical properties between CT- and VT-TALEs revealed that VT-TALE
      has a larger amplitude motion along the superhelical axis (superhelical motion)
      compared with CT-TALE. The greater superhelical motion in VT-TALE enabled more
      TAL-repeats to engage in the target sequence recognition compared with CT-TALE.
      The extended sequence recognition by the TAL-repeats improves site specificity
      with limiting the spatial distribution of FokI domains to facilitate their
      dimerization at the desired site. Molecular dynamics simulations revealed that
      the non-RVD mutations alter inter-repeat hydrogen bonding to amplify the
      superhelical motion of VT-TALE. The TALEN activity is associated with the inter
      repeat hydrogen bonding among the TAL repeats.

PMID- 27883075
TI  - Direct electrical control of IgG conformation and functional activity at
      surfaces.
AB  - We have devised a supramolecular edifice involving His-tagged protein A and
      antibodies to yield surface immobilized, uniformly oriented, IgG-type, antibody
      layers with Fab fragments exposed off an electrode surface. We demonstrate here
      that we can affect the conformation of IgGs, likely pushing/pulling
      electrostatically Fab fragments towards/from the electrode surface. A potential
      difference between electrode and solution acts on IgGs' charged aminoacids
      modulating the accessibility of the specific recognition regions of Fab fragments
      by antigens in solution. Consequently, antibody-antigen affinity is affected by
      the sign of the applied potential: a positive potential enables an effective
      capture of antigens; a negative one pulls the fragments towards the electrode,
      where steric hindrance caused by neighboring molecules largely hampers the
      capture of antigens. Different experimental techniques (electrochemical quartz
      crystal microbalance, electrochemical impedance spectroscopy, fluorescence
      confocal microscopy and electrochemical atomic force spectroscopy) were used to
      evaluate binding kinetics, surface coverage, effect of the applied electric field
      on IgGs, and role of charged residues on the phenomenon described. These findings
      expand the concept of electrical control of biological reactions and can be used
      to gate electrically specific recognition reactions with impact in biosensors,
      bioactuators, smart biodevices, nanomedicine, and fundamental studies related to
      chemical reaction kinetics.

PMID- 27883080
TI  - Construction of a Miniaturized Chromatic Acclimation Sensor from Cyanobacteria
      with Reversed Response to a Light Signal.
AB  - Cyanobacteria harbor unique photoreceptors, designated as cyanobacteriochromes
      (CBCRs). In this study, we attempted to engineer the chromatic acclimation sensor
      CcaS, a CBCR derived from the cyanobacterium Synechocystis sp. PCC 6803. The wild
      type CcaS induces gene expression under green light illumination and represses it
      under red light illumination. We focused on the domain structure of CcaS, which
      consists of an N-terminal transmembrane helix; a GAF domain, which serves as the
      sensor domain; a linker region (L1); two PAS domains; a second linker region
      (L2); and a C-terminal histidine kinase (HK) domain. Truncated versions of the
      photoreceptor were constructed by removing the L1 linker region and the two PAS
      domains, and fusing the GAF and HK domains with a truncated linker region. Thus
      constructed "miniaturized CcaSs" were grouped into four distinct categories
      according to their responses toward green and red light illumination, with some
      showing improved gene regulation compared to the wild type. Remarkably, one of
      the miniaturized CcaSs induced gene expression under red light and repressed it
      under green light, a reversed response to the light signal compared to wild type
      CcaS. These characteristics of engineered photoreceptors were discussed by
      analyzing the CcaS structural model.

PMID- 27883071
TI  - Mint3/Apba3 depletion ameliorates severe murine influenza pneumonia and
      macrophage cytokine production in response to the influenza virus.
AB  - Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies
      have suggested that excessive activation of the host immune system including
      macrophages is responsible for the severe pathologies mediated by IFV infection.
      Here, we focused on the X11 protein family member Mint3/Apba3, known to promote
      ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in
      macrophages, and examined its roles in lung pathogenesis and anti-viral defence
      upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia
      with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration
      in the IFV-infected lungs without alteration in viral burden, type-I interferon
      production, or acquired immunity. In macrophages, Mint3 depletion attenuated NF
      kappaB signalling and the resultant cytokine/chemokine production in response to
      IFV infection by increasing IkappaBalpha and activating the cellular energy
      sensor AMPK, respectively. Thus, Mint3 might represent one of the likely
      therapeutic targets for the treatment of severe influenza pneumonia without
      affecting host anti-viral defence through suppressing macrophage
      cytokine/chemokine production.

PMID- 27883083
TI  - Refractive Index and Absorption Attribution of Highly Absorbing Brown Carbon
      Aerosols from an Urban Indian City-Kanpur.
AB  - Atmospheric aerosols influence Earth's radiative balance, having both warming and
      cooling effects. Though many aerosols reflect radiation, carbonaceous aerosols
      such as black carbon and certain organic carbon species known as brown carbon
      have the potential to warm the atmosphere by absorbing light. Black carbon
      absorbs light over the entire solar spectrum whereas brown carbon absorbs near-UV
      wavelengths and, to a lesser extent, visible light. In developing countries, such
      as India, where combustion sources are prolific, the influence of brown carbon on
      absorption may be significant. In order to better characterize brown carbon, we
      present experimental and modeled absorption properties of submicron aerosols
      measured in an urban Indian city (Kanpur). Brown carbon here is found to be
      fivefold more absorbing at 365 nm wavelength compared to previous studies.
      Results suggest ~30% of total absorption in Kanpur is attributed to brown carbon,
      with primary organic aerosols contributing more than secondary organics. We
      report the spectral brown carbon refractive indices along with an experimentally
      constrained estimate of the influence of aerosol mixing state on absorption. We
      conclude that brown carbon in Kanpur is highly absorbing in nature and that the
      mixing state plays an important role in light absorption from volatile species.

PMID- 27883076
TI  - A CRISPR-Cas9 Assisted Non-Homologous End-Joining Strategy for One-step
      Engineering of Bacterial Genome.
AB  - Homologous recombination-mediated genome engineering has been broadly applied in
      prokaryotes with high efficiency and accuracy. However, this method is limited in
      realizing larger-scale genome editing with numerous genes or large DNA fragments
      because of the relatively complicated procedure for DNA editing template
      construction. Here, we describe a CRISPR-Cas9 assisted non-homologous end-joining
      (CA-NHEJ) strategy for the rapid and efficient inactivation of bacterial gene (s)
      in a homologous recombination-independent manner and without the use of selective
      marker. Our study show that CA-NHEJ can be used to delete large chromosomal DNA
      fragments in a single step that does not require homologous DNA template. It is
      thus a novel and powerful tool for bacterial genomes reducing and possesses the
      potential for accelerating the genome evolution.

PMID- 27883074
TI  - Adipose Stem Cells Display Higher Regenerative Capacities and More Adaptable
      Electro-Kinetic Properties Compared to Bone Marrow-Derived Mesenchymal Stromal
      Cells.
AB  - Adipose stem cells (ASCs) have recently emerged as a more viable source for
      clinical applications, compared to bone-marrow mesenchymal stromal cells (BM
      MSCs) because of their abundance and easy access. In this study we evaluated the
      regenerative potency of ASCs compared to BM-MSCs. Furthermore, we compared the
      dielectric and electro-kinetic properties of both types of cells using a novel
      Dielectrophoresis (DEP) microfluidic platform based on a printed circuit board
      (PCB) technology. Our data show that ASCs were more effective than BM-MSCs in
      promoting neovascularization in an animal model of hind-limb ischemia. When
      compared to BM-MSCs, ASCs displayed higher resistance to hypoxia-induced
      apoptosis, and to oxidative stress-induced senescence, and showed more potent
      proangiogenic activity. mRNA expression analysis showed that ASCs had a higher
      expression of Oct4 and VEGF than BM-MSCs. Furthermore, ASCs showed a remarkably
      higher telomerase activity. Analysis of the electro-kinetic properties showed
      that ASCs displayed different traveling wave velocity and rotational speed
      compared to BM-MSCs. Interestingly, ASCs seem to develop an adaptive response
      when exposed to repeated electric field stimulation. These data provide new
      insights into the physiology of ASCs, and evidence to their potential superior
      potency compared to marrow MSCs as a source of stem cells.

PMID- 27883079
TI  - A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models
      of Type 1 diabetes and multiple sclerosis.
AB  - Helminth parasites secrete molecules that potently modulate the immune responses
      of their hosts and, therefore, have potential for the treatment of immune
      mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth
      parasite Fasciola hepatica, ameliorated disease in two different murine models of
      autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated
      demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation
      of auto-antigen specific T cells or their production of cytokines. However, in
      both conditions, the reduction in clinical symptoms was associated with the
      absence of immune cell infiltrates in the target organ (islets and the brain
      tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide
      interacted with macrophages and reduced their capacity to secrete pro
      inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of
      innate pro-inflammatory immune responses, which are central to the initiation of
      autoimmunity in both diseases, prevented the trafficking of autoreactive
      lymphocytes from the periphery to the site of autoimmunity (as opposed to
      directly modulating their function per se), and thus prevented tissue
      destruction. The ability of FhHDM-1 to modulate macrophage function, combined
      with its efficacy in disease prevention in multiple models, suggests that FhHDM-1
      has considerable potential as a treatment for autoimmune diseases.

PMID- 27883078
TI  - Impaired Endothelial Nitric Oxide Synthase Homodimer Formation Triggers
      Development of Transplant Vasculopathy - Insights from a Murine Aortic
      Transplantation Model.
AB  - Transplant vasculopathy (TV) represents a major obstacle to long-term graft
      survival and correlates with severity of ischemia reperfusion injury (IRI). Donor
      administration of the nitric oxide synthases (NOS) co-factor tetrahydrobiopterin
      has been shown to prevent IRI. Herein, we analysed whether tetrahydrobiopterin is
      also involved in TV development. Using a fully allogeneic mismatched (BALB/c to
      C57BL/6) murine aortic transplantation model grafts subjected to long cold
      ischemia time developed severe TV with intimal hyperplasia (alpha-smooth muscle
      actin positive cells in the neointima) and endothelial activation (increased P
      selectin expression). Donor pretreatment with tetrahydrobiopterin significantly
      minimised these changes resulting in only marginal TV development. Severe TV
      observed in the non-treated group was associated with increased protein oxidation
      and increased occurrence of endothelial NOS monomers in the aortic grafts already
      during graft procurement. Tetrahydrobiopterin supplementation of the donor
      prevented all these early oxidative changes in the graft. Non-treated allogeneic
      grafts without cold ischemia time and syngeneic grafts did not develop any TV. We
      identified early protein oxidation and impaired endothelial NOS homodimer
      formation as plausible mechanistic explanation for the crucial role of IRI in
      triggering TV in transplanted aortic grafts. Therefore, targeting endothelial NOS
      in the donor represents a promising strategy to minimise TV.

PMID- 27883082
TI  - Alpha band disruption in the AD-continuum starts in the Subjective Cognitive
      Decline stage: a MEG study.
AB  - The consideration of Subjective Cognitive Decline (SCD) as a preclinical stage of
      AD remains still a matter of debate. Alpha band alterations represent one of the
      most significant changes in the electrophysiological profile of AD. In
      particular, AD patients exhibit reduced alpha relative power and frequency. We
      used alpha band activity measured with MEG to study whether SCD and MCI elders
      present these electrophysiological changes characteristic of AD, and to determine
      the evolution of the observed alterations across AD spectrum. The total sample
      consisted of 131 participants: 39 elders without SCD, 41 elders with SCD and 51
      MCI patients. All of them underwent MEG and MRI scans and neuropsychological
      assessment. SCD and MCI patients exhibited a similar reduction in alpha band
      activity compared with the no SCD group. However, only MCI patients showed a
      slowing in their alpha peak frequency compared with both SCD and no SCD. These
      changes in alpha band were related to worse cognition. Our results suggest that
      AD-related alterations may start in the SCD stage, with a reduction in alpha
      relative power. It is later, in the MCI stage, where the slowing of the spectral
      profile takes place, giving rise to objective deficits in cognitive functioning.

PMID- 27883081
TI  - V(D)J recombination process and the Pre-B to immature B-cells transition are
      altered in Fanca-/- mice.
AB  - B-lymphocytes in the bone marrow (BM) must generate a functional B-cell receptor
      and overcome the negative selection induced by reactivity with autoantigens. Two
      rounds of DNA recombination are required for the production of functional
      immunoglobulin heavy (Ig-HCs) and light (LCs) chains necessary for the
      continuation of B-lymphocyte development in the BM. Both rounds depend on the
      joint action of recombination activating gene-1 (RAG-1) and RAG-2 endonucleases
      with the DNA non-homologous end-joining pathway. Loss of the FANC gene leads to
      the chromosome breakage and cancer predisposition syndrome Fanconi anemia.
      Because the FANC proteins are involved in certain aspects of the recombination
      process, we sought to determine the impact of the FANC pathway on the Ig
      diversification process using Fanca-/- mice. In this work we demonstrated that
      Fanca-/- animals have a mild B-cell differentiation defect characterized by a
      specific alteration of the IgM- to IgM+ transition of the B220low B-cell
      population. Pre-B cells from Fanca-/- mice show evidence of impaired kLC
      rearrangement at the level of the Vk-Jk junction. Furthermore, Fanca-/- mice
      showed a skewed Vkappa gene usage during formation of the LCs Vk-Jk junctions.
      Therefore, the Fanca protein appears as a yet unidentified factor involved in the
      primary diversification of Ig.

PMID- 27883085
TI  - Phenotypic and functional characterization of the major lymphocyte populations in
      the fruit-eating bat Pteropus alecto.
AB  - The unique ability of bats to act as reservoir for viruses that are highly
      pathogenic to humans suggests unique properties and functional characteristics of
      their immune system. However, the lack of bat specific reagents, in particular
      antibodies, has limited our knowledge of bat's immunity. Using cross-reactive
      antibodies, we report the phenotypic and functional characterization of T cell
      subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings
      indicate the predominance of CD8+ T cells in the spleen from wild-caught bats
      that may reflect either the presence of viruses in this organ or predominance of
      this cell subset at steady state. Instead majority of T cells in circulation,
      lymph nodes and bone marrow (BM) were CD4+ subsets. Interestingly, 40% of spleen
      T cells expressed constitutively IL-17, IL-22 and TGF-beta mRNA, which may
      indicate a strong bias towards the Th17 and regulatory T cell subsets.
      Furthermore, the unexpected high number of T cells in bats BM could suggest an
      important role in T cell development. Finally, mitogenic stimulation induced
      proliferation and production of effector molecules by bats immune cells. This
      work contributes to a better understanding of bat's immunity, opening up new
      perspectives of therapeutic interventions for humans.

PMID- 27883084
TI  - Nucleoside-Diphosphate-Kinase of P. gingivalis is Secreted from Epithelial Cells
      In the Absence of a Leader Sequence Through a Pannexin-1 Interactome.
AB  - Nucleoside-diphosphate-kinases (NDKs) are leaderless, multifunctional enzymes.
      The mode(s) of NDK secretion is currently undefined, while extracellular
      translocation of bacterial NDKs is critical for avoidance of host pathogen
      clearance by opportunistic pathogens such as Porphyromonas gingivalis. P.
      gingivalis-NDK during infection inhibits extracellular-ATP (eATP)/P2X7-receptor
      mediated cell death in gingival epithelial cells (GECs) via eATP hydrolysis.
      Furthermore, depletion of pannexin-1-hemichannel (PNX1) coupled with P2X7
      receptor blocks the infection-induced eATP release in GECs, and P. gingivalis-NDK
      impacts this pathway. Ultrastructural and confocal microscopy of P. gingivalis-co
      cultured GECs or green-fluorescent-protein (GFP)-P. gingivalis-NDK transfected
      GECs revealed a perinuclear/cytoplasmic localization of NDK. eATP stimulation
      induced NDK recruitment to the cell periphery. Depletion of PNX1 by siRNA or
      inhibition by probenecid resulted in significant blocking of extracellular NDK
      activity and secretion using ATPase and ELISA assays. Co-immunoprecipitation
      coupled Mass-spectrometry method revealed association of P. gingivalis-NDK to the
      myosin-9 motor molecule. Interestingly, inhibition of myosin-9, actin, and lipid
      rafts, shown to be involved in PNX1-hemichannel function, resulted in marked
      intracellular accumulation of NDK and decreased NDK secretion from infected GECs.
      These results elucidate for the first time PNX1-hemichannels as potentially main
      extracellular translocation pathway for NDKs from an intracellular pathogen,
      suggesting that PNX1-hemichannels may represent a therapeutic target for chronic
      opportunistic infections.

PMID- 27883088
TI  - Meta-adaptation in the auditory midbrain under cortical influence.
AB  - Neural adaptation is central to sensation. Neurons in auditory midbrain, for
      example, rapidly adapt their firing rates to enhance coding precision of common
      sound intensities. However, it remains unknown whether this adaptation is fixed,
      or dynamic and dependent on experience. Here, using guinea pigs as animal models,
      we report that adaptation accelerates when an environment is re-encountered-in
      response to a sound environment that repeatedly switches between quiet and loud,
      midbrain neurons accrue experience to find an efficient code more rapidly. This
      phenomenon, which we term meta-adaptation, suggests a top-down influence on the
      midbrain. To test this, we inactivate auditory cortex and find acceleration of
      adaptation with experience is attenuated, indicating a role for cortex-and its
      little-understood projections to the midbrain-in modulating meta-adaptation.
      Given the prevalence of adaptation across organisms and senses, meta-adaptation
      might be similarly common, with extensive implications for understanding how
      neurons encode the rapidly changing environments of the real world.

PMID- 27883087
TI  - Inter-annual maintenance of the fine-scale genetic structure in a biennial plant.
AB  - Within plant populations, space-restricted gene movement, together with
      environmental heterogeneity, can result in a spatial variation in gene
      frequencies. In biennial plants, inter-annual flowering migrants can homogenize
      gene frequencies between consecutive cohorts. However, the actual impact of these
      migrants on spatial genetic variation remains unexplored. Here, we used 10
      nuclear microsatellite and one plastid genetic marker to characterize the spatial
      genetic structure within two consecutive cohorts in a population of the biennial
      plant Erysimum mediohispanicum (Brassicaceae). We explored the maintenance of
      this structure between consecutive flowering cohorts at different levels of
      complexity, and investigated landscape effects on gene flow. We found that
      cohorts were not genetically differentiated and showed a spatial genetic
      structure defined by a negative genetic-spatial correlation at fine scale that
      varied in intensity with compass directions. This spatial genetic structure was
      maintained when comparing plants from different cohorts. Additionally, genotypes
      were consistently associated with environmental factors such as light
      availability and soil composition, but to a lesser extent compared with the
      spatial autocorrelation. We conclude that inter-annual migrants, in combination
      with limited seed dispersal and environmental heterogeneity, play a major role in
      shaping and maintaining the spatial genetic structure among cohorts in this
      biennial plant.

PMID- 27883089
TI  - Hydrogen Sulfide and/or Ammonia Reduces Spermatozoa Motility through AMPK/AKT
      Related Pathways.
AB  - A number of emerging studies suggest that air pollutants such as hydrogen sulfide
      (H2S) and ammonia (NH3) may cause a decline in spermatozoa motility. The impact
      and underlying mechanisms are currently unknown. Boar spermatozoa (in vitro) and
      peripubertal male mice (in vivo) were exposed to H2S and/or NH3 to evaluate the
      impact on spermatozoa motility. Na2S and/or NH4Cl reduced the motility of boar
      spermatozoa in vitro. Na2S and/or NH4Cl disrupted multiple signaling pathways
      including decreasing Na+/K+ ATPase activity and protein kinase B (AKT) levels,
      activating Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and
      phosphatase and tensin homolog deleted on chromosome ten (PTEN), and increasing
      reactive oxygen species (ROS) to diminish boar spermatozoa motility. The increase
      in ROS might have activated PTEN, which in turn diminished AKT activation. The
      ATP deficiency (indicated by reduction in Na+/K+ ATPase activity), transforming
      growth factor (TGFbeta) activated kinase-1 (TAK1) activation, and AKT
      deactivation stimulated AMPK, which caused a decline in boar spermatozoa
      motility. Simultaneously, the deactivation of AKT might play some role in the
      reduction of boar spermatozoa motility. Furthermore, Na2S and/or NH4Cl declined
      the motility of mouse spermatozoa without affecting mouse body weight gain in
      vivo. Findings of the present study suggest that H2S and/or NH3 are adversely
      associated with spermatozoa motility.

PMID- 27883092
TI  - Spatial mapping of lichen specialized metabolites using LDI-MSI: chemical ecology
      issues for Ophioparma ventosa.
AB  - Imaging mass spectrometry techniques have become a powerful strategy to assess
      the spatial distribution of metabolites in biological systems. Based on auto
      ionisability of lichen metabolites using LDI-MS, we herein image the distribution
      of major secondary metabolites (specialized metabolites) from the lichen
      Ophioparma ventosa by LDI-MSI (Mass Spectrometry Imaging). Such technologies
      offer tremendous opportunities to discuss the role of natural products through
      spatial mapping, their distribution patterns being consistent with previous
      chemical ecology reports. A special attention was dedicated to miriquidic acid,
      an unexpected molecule we first reported in Ophioparma ventosa. The analytical
      strategy presented herein offers new perspectives to access the sharp
      distribution of lichen metabolites from regular razor blade-sectioned slices.

PMID- 27883093
TI  - A finger on the pulse.

PMID- 27883086
TI  - An In Silico study of TiO2 nanoparticles interaction with twenty standard amino
      acids in aqueous solution.
AB  - Titanium dioxide (TiO2) is probably one of the most widely used nanomaterials,
      and its extensive exposure may result in potentially adverse biological effects.
      Yet, the underlying mechanisms of interaction involving TiO2 NPs and
      macromolecules, e.g., proteins, are still not well understood. Here, we perform
      all-atom molecular dynamics simulations to investigate the interactions between
      TiO2 NPs and the twenty standard amino acids in aqueous solution exploiting a
      newly developed TiO2 force field. We found that charged amino acids play a
      dominant role during the process of binding to the TiO2 surface, with both basic
      and acidic residues overwhelmingly preferred over the non-charged counterparts.
      By calculating the Potential Mean Force, we showed that Arg is prone to direct
      binding onto the NP surface, while Lys needs to overcome a ~2 kT free energy
      barrier. On the other hand, acidic residues tend to form "water bridges" between
      their sidechains and TiO2 surface, thus displaying an indirect binding. Moreover,
      the overall preferred positions and configurations of different residues are
      highly dependent on properties of the first and second solvation water. These
      molecular insights learned from this work might help with a better understanding
      of the interactions between biomolecules and nanomaterials.

PMID- 27883094
TI  - ?

PMID- 27883096
TI  - ?

PMID- 27883097
TI  - ?

PMID- 27883095
TI  - ?

PMID- 27883098
TI  - ?

PMID- 27883099
TI  - A meaningless doctors' strike?

PMID- 27883101
TI  - ?

PMID- 27883090
TI  - Sphingosine 1-phosphate lyase ablation disrupts presynaptic architecture and
      function via an ubiquitin- proteasome mediated mechanism.
AB  - The bioactive lipid sphingosine 1-phosphate (S1P) is a degradation product of
      sphingolipids that are particularly abundant in neurons. We have shown previously
      that neuronal S1P accumulation is toxic leading to ER-stress and an increase in
      intracellular calcium. To clarify the neuronal function of S1P, we generated
      brain-specific knockout mouse models in which S1P-lyase (SPL), the enzyme
      responsible for irreversible S1P cleavage was inactivated. Constitutive ablation
      of SPL in the brain (SPLfl/fl/Nes) but not postnatal neuronal forebrain
      restricted SPL deletion (SPLfl/fl/CaMK) caused marked accumulation of S1P. Hence,
      altered presynaptic architecture including a significant decrease in number and
      density of synaptic vesicles, decreased expression of several presynaptic
      proteins, and impaired synaptic short term plasticity were observed in
      hippocampal neurons from SPLfl/fl/Nes mice. Accordingly, these mice displayed
      cognitive deficits. At the molecular level, an activation of the ubiquitin
      proteasome system (UPS) was detected which resulted in a decreased expression of
      the deubiquitinating enzyme USP14 and several presynaptic proteins. Upon
      inhibition of proteasomal activity, USP14 levels, expression of presynaptic
      proteins and synaptic function were restored. These findings identify S1P
      metabolism as a novel player in modulating synaptic architecture and plasticity.

PMID- 27883091
TI  - Mycobacterium tuberculosis-triggered Hippo pathway orchestrates CXCL1/2
      expression to modulate host immune responses.
AB  - Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely
      regulated alterations within the host which eventually coin the outcome of
      infection. Chemokines are important components in directing immune cell
      recruitment to the site of infection, and shaping the disease progression. Here,
      we demonstrate that Hippo (mammalian sterile 20-like 1 and 2 kinases, MST1/2, in
      mammals), is activated during mycobacterial infection in a toll-like receptor
      (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner. Mtb
      triggered Hippo signaling modulates the expression and secretion of chemokines
      (CXCL1 and CXCL2); as silencing MST1/2 compromised the ability of Mtb to furnish
      the same. Further insight into the mechanism of Hippo-mediated regulation of
      chemokines revealed the role for a non-canonical Hippo effector interferon (IFN)
      regulatory factor (IRF) 3 in the process and marked the effect to be independent
      of LATS1. Alongside their ability to guide directed recruitment of immune cells,
      we have uncovered a paracrine role for Hippo-mediated secretion of CXCL1 and
      CXCL2 in the production of anti-microbial peptides (beta-defensins), iNOS, NOX2
      and pro-inflammatory molecules during mycobacterial infection of the host. This
      study highlights the involvement of TLR2-IRAK1/4-MST1/2-IRF3 axis in Mtb
      triggered modulation of chemokines and identifies Hippo signaling as a novel
      regulator of host-mycobacterial interactions.

PMID- 27883100
TI  - [Discrimination is rarely a golden mean].

PMID- 27883103
TI  - [Gout - new approaches to diagnostics and treatment].
AB  - An attack of gout is extremely painful. Recurrent attacks of arthritis in one or
      more joints or tendon sheaths accompanied by intense pain are typical of this
      commonly occurring condition. As these symptoms indicate acute inflammation due
      to uric acid crystal deposition, good diagnostics are essential to enable
      initiation of drug treatment which removes the crystals deposited in tissue.

PMID- 27883102
TI  - Patients with burn injuries admitted to Norwegian hospitals - a population-based
      study.
AB  - BACKGROUND: The objective of this article is to elucidate the scope of burn
      injuries in Norway, on the basis of those patients who had sustained a burn
      injury that caused hospitalisation through a calendar year. MATERIAL AND METHOD:
      The article is based on data retrieved from the Norwegian Patient Registry on
      patients discharged from Norwegian hospitals in 2012 with a burn injury as their
      main diagnosis, supplemented with activity data for children admitted to the Burn
      Unit, Haukeland University Hospital, Bergen, during the period 2013 - 15.
      RESULTS: In 2012, altogether 620 people (12.4/100 000 inhabitants) were
      hospitalised with burn injuries. Of these patients, 393 (63.4 %) were men. A
      total of 375 patients (60 %) were hospitalised more than once, and 124 (20 %)
      were admitted to more than one hospital. Altogether 367 patients (59 %) were
      hospitalised for less than eight days. Average hospitalisation time for the group
      as a whole was 11.3 days (SD 18.8 days). Many of the burn-injured patients were
      young: the average age was 27.4 years (SD 26.0 years). As many as 183 patients
      (30 %) were less than three years old. Children in this age group were admitted
      for burn injuries 12 times more frequently than children >= 5 years and adults.
      INTERPRETATION: We found no definite reduction in burn injuries as a cause for
      admission to Norwegian hospitals in 2012 when compared to results from previous
      studies for the period 1992 - 2007. There ought to be a major potential for more
      effective prevention of burn injuries in the age group < 3 years, in which
      scalding (78 %) and contact with hot surfaces (most often stoves) (17 %) are the
      main mechanisms of injury.

PMID- 27883104
TI  - [Radiation-induced cataracts].
AB  - The dose limit for the lens of the eye for occupationally exposed workers that is
      stipulated in the Norwegian Regulation on radiation protection is based on
      outdated threshold doses for radiation-induced cataracts. Recent studies have
      shown that injuries may occur at significantly lower radiation doses than
      previously assumed. The results from the new studies will impact upon future
      legislation and recommendations regarding radiation hygiene for personnel in x
      ray laboratories and operating theatres who may be exposed to significant
      radiation doses in the course of their work.

PMID- 27883105
TI  - [An unusual sports injury].

PMID- 27883106
TI  - The woman who did not recognise her own face.

PMID- 27883107
TI  - [A man in his 40s with diabetes, enlarged lacrimal gland and kidney failure].

PMID- 27883108
TI  - [More than just good stories].

PMID- 27883109
TI  - New reference charts for weight-related body measurements in children.

PMID- 27883110
TI  - [Prodrugs].

PMID- 27883111
TI  - ?

PMID- 27883112
TI  - ?

PMID- 27883113
TI  - ?

PMID- 27883114
TI  - ?

PMID- 27883115
TI  - Lifitegrast: First LFA-1/ICAM-1 antagonist for treatment of dry eye disease.
AB  - Dry eye disease is an extremely common condition affecting millions worldwide.
      The underlying pathophysiological mechanism is thought to be localized
      inflammation of the ocular surface resulting in the localization of T cells at
      this surface followed by their activation and subsequent liberation of cytokines.
      This effect on T cells results from the binding of lymphocyte function-associated
      antigen-1 (LFA-1) located on T cells to intercellular adhesion molecule 1 (ICAM
      1) expressed on inflamed epithelium and endothelium, and on T cells. Lifitegrast
      is a T-cell integrin antagonist designed to mimic ICAM-1, thus blocking the
      interaction of LFA-1 and ICAM-1. Lifitegrast enters the systemic circulation to a
      limited extent thus reducing the likelihood of unwanted systemic reactions.
      Clinical trials in over 2,500 subjects with dry eye disease have shown that 5.0%
      lifitegrast given by ocular instillation causes a significant reduction in
      objective and subjective signs and symptoms of the disease. These beneficial
      effects are associated with a relatively low incidence of unwanted effects,
      almost all local in nature. In light of these findings, lifitegrast was approved
      by the Food and Drug Administration (FDA) in 2016 for the treatment of dry eye
      disease, the first drug with this mechanism of action to be so approved.

PMID- 27883116
TI  - Zabofloxacin for chronic bronchitis.
AB  - Treatment of lower respiratory tract infection poses as an ongoing challenge
      among respiratory tract diseases. Bacterial infections are causes of acute
      exacerbations in chronic bronchitis and indications for antibacterial therapy.
      Several antibiotics were applied to treat bacterial infections in chronic
      bronchitis, among them fluoroquinolones are considered potent, broad-spectrum
      agents with excellent tissue penetration. This monograph focuses on zabofloxacin,
      a novel fluoroquinolone agent recently approved and launched in South Korea, and
      summarizes the drug's antibacterial efficacy, pharmacokinetic properties and
      toxicity. Recent advances concerning fluoroquinolones in chronic bronchitis will
      be discussed, along with a comparison between zabofloxacin and moxifloxacin.
      Zabofloxacin has proved to be noninferior to moxifloxacin against major community
      acquired Gram-positive and Gram-negative respiratory tract pathogens and found to
      be well tolerated in both oral and parenteral administrations. These features can
      make it a potential antimicrobial agent in therapy of chronic bronchitis and
      other lower respiratory tract infections.

PMID- 27883118
TI  - Cachexia.
AB  - Cachexia is a multiorgan, multifactorial and often irreversible wasting syndrome
      associated with cancer and other serious, chronic illnesses including AIDS,
      chronic heart failure, chronic kidney disease and chronic obstructive pulmonary
      disease. Treatment of the patient with cachexia is currently targeted to
      correcting the two underlying features of the condition: anorexia and metabolic
      disturbances. Greater understanding of the mechanisms behind cachexia and muscle
      wasting have led to new therapeutic possibilities, however. Several classes of
      drugs are under active development for cachexia including drugs acting on hormone
      receptors or cytokine receptors, myostatin/activin pathway antagonists, beta
      adrenoceptor agonists and cannabinoids. This review will cover the
      pathophysiology, epidemiology, diagnosis, treatment, drug candidates under active
      development and targets for therapeutic intervention of cachexia.

PMID- 27883117
TI  - Combination therapies for improved management of lower urinary tract
      symptoms/benign prostatic hyperplasia.
AB  - Several urological and non-urological conditions can contribute to the onset of
      lower urinary tract symptoms (LUTS), including benign prostatic hyperplasia
      (BPH), which is one of the main underlying causes in male patients. Six
      pharmacological classes (alpha-adrenoceptor blockers [ABs], 5alpha-reductase
      inhibitors [5ARIs], phytotherapeutics, antimuscarinics [AMs], beta3-adrenoceptor
      agonists and phosphodiesterase type 5 inhibitors [PDE5Is]) are available, alone
      or in combination, for the treatment of male LUTS. The aim of this review is to
      summarize the latest evidence on combination medical treatments for male patients
      with LUTS/BPH. Standard combinations include AB + 5ARI (for patients with
      increased prostate volume who are at risk for BPH progression); AB + PDE5I (for
      patients with concomitant erectile dysfunction); and AB + AM or beta3 agonist
      (for patients with persistent storage symptoms and not at risk for acute urinary
      retention). Other possible multidrug treatments have been proposed in preliminary
      studies, but further randomized controlled trials are needed to determine whether
      these putative strategies will eventually be considered a new standard for
      patients with LUTS/BPH. The possibility of tailoring BPH treatment according to
      different patient characteristics and expectations, using two or more drugs,
      seems a promising path in the field of LUTS/BPH management; however, physicians
      should consider the risk of increasing costs without proven long-term efficacy
      with most of these combination treatments.

PMID- 27883122
TI  - Two-dimensional optical spectroscopy of homo- and heterodimers.
AB  - We theoretically study the two-dimensional (2D) spectroscopy of molecular dimers.
      The spectra are first analyzed within an electronic level model. It is
      demonstrated how the angular average over molecular orientations influences the
      features of the spectra. Methods to calculate angular averaged vibronic spectra
      within perturbation theory are compared. We systematically document changes in
      the 2D-spectra upon going from homo- to heterodimers. In particular, it is
      demonstrated that large-amplitude off-diagonal peaks appear for heterodimers even
      in the limit of vanishing coupling. This is related to the difference in the
      excitation energies of the two different monomers. For homodimers with equal
      monomer excitation energies, such peaks become diagonal peaks and thus cannot be
      isolated.

PMID- 27883119
TI  - GTCBio's Precision Medicine Conference (July 7-8, 2016 - Boston, Massachusetts,
      USA).
AB  - GTCBio's Precision Medicine Conference met this year to outline the many steps
      forward that precision medicine and individualized genomics has made and the
      challenges it still faces in technological, modeling, and standards development,
      interoperability and compatibility advancements, and methods of economic and
      societal adoption. The conference was split into four sections, 'Overcoming
      Challenges in the Commercialization of Precision Medicine', 'Implementation of
      Precision Medicine: Strategies & Technologies', 'Integrating & Interpreting
      Personal Genomics, Big Data, & Bioinformatics' and 'Incentivizing Precision
      Medicine: Regulation & Reimbursement', with this report focusing on the final two
      subjects.

PMID- 27883123
TI  - A study of trap and recombination centers in MAPbI3 perovskites.
AB  - Trapping and recombination processes in thin films of CH3NH3PbI3 (MAPbI3) were
      studied by means of transient photoconductivity measurements and theoretical
      simulations of the relaxation curves resulting from the photocurrent
      measurements; in particular, the influence of temperature as well as of the
      sample temperature and intensity of illumination and pressure inside the
      measurement system on the photoconductivity response, were studied. The
      experimental curves of photocurrent were analyzed using the real part of the
      Fourier transform. The study revealed that the photocurrent of the MAPbI3 films,
      measured at atmospheric pressure, is mainly governed by surface related processes
      induced by chemisorption and desorption of oxygen, whereas the photocurrent
      resulting from measurements performed in a vacuum is mainly governed by bulk
      related processes. It was found that, in general, the photocurrent response is
      affected by both trap assisted fast recombination processes and traps whose
      activation process is delayed, with the contribution in the intensity of the
      photocurrent of the first process being greater that of the second one. Evidence
      that the MAPbI3 film exhibits a deep trap state at around 459 meV attributed to
      trap assisted recombination was found; furthermore, the MAPbI3 films present
      shallow trap states at 129 and 24 meV that correspond to trap states whose
      activation process is delayed.

PMID- 27883125
TI  - Surface induced vibrational modes in the fluorescence spectra of PTCDA adsorbed
      on the KCl(100) and NaCl(100) surfaces.
AB  - We report a combined experiment-theory study on low energy vibrational modes in
      fluorescence spectra of perylene-3,4,9,10-tetracarboxylic acid dianhydride
      (PTCDA) molecules. Using very low coverages, isolated molecules were adsorbed on
      terrace sites or at sites located at residual steps on (100) oriented alkali
      halide films (KCl and NaCl). The low energy modes couple to the optical
      transition only because the PTCDA molecule is geometrically distorted (C2v) upon
      adsorption on the surface; they would be absent for the parent planar (D2h) PTCDA
      molecule. The modes differ in number and energy for molecules adsorbed on regular
      terrace sites and molecules adsorbed at step edge sites. Modes appearing for step
      edge sites have the character of frustrated rotations. Their coupling to the
      optical transition is a consequence of the further reduced symmetry of the step
      edge sites. We find a larger number of vibrational modes on NaCl than on KCl. We
      explain this by the stronger electrostatic bonding of the PTCDA on NaCl compared
      to KCl. It causes the optical transition to induce stronger changes in the
      molecular coordinates, thus leading to larger Franck-Condon factors and thus
      stronger coupling. Our results demonstrate how optical spectroscopy can be used
      to gain information on adsorption sites of molecules at low surface
      concentrations.

PMID- 27883126
TI  - Proton diffusion dynamics along a diol as a proton-conducting wire in a photo
      amphiprotic model system.
AB  - We investigated the dynamics of excited-state proton transfer (ESPT) of photo
      amphiprotic 7-hydroxyquinoline (7HQ) in the presence of a hydrogen (H)-bond
      bridging diol in a polar aprotic medium. The formation of 1 : 1 H-bonded
      complexes of 7HQ with various diols of different alkane chain lengths was
      revealed using steady-state electronic spectroscopy. With femtosecond-resolved
      fluorescence spectroscopy, cyclic H-bonded 1 : 1 complexes were found to undergo
      facile ESPT from the acidic enol to the basic imine group of 7HQ via the H-bond
      bridge. Through quantum chemical calculations, we found that the proton-transfer
      rate of the well-configured H-bonded complex correlated with the intramolecular H
      bond length of a H-bond wiring diol molecule. Noncyclic, singly H-bonded 7HQ with
      a diol molecule was observed to undergo ESPT once another diol molecule diffuses
      to the noncyclic complex and accomplishes the formation of a reactive cyclic H
      bonded 7HQ-(diol)2 complex, which was evidenced by the observation that the
      overall proton-transfer rate constant decreases when a longer-chain diol was used
      as the bridging wire part. The kinetic isotope effect on the proton relay was
      investigated to confirm that the nature of the activation barrier for the proton
      diffusion along the wire is isotope-sensitive proton tunnelling, while for the
      non-cyclic configuration, the isotope-insensitive H-bond bridge formation is a
      prerequisite for ESPT.

PMID- 27883127
TI  - Enhanced perovskite morphology and crystallinity for high performance perovskite
      solar cells using a porous hole transport layer from polystyrene nanospheres.
AB  - : Organic-inorganic metal halide perovskites have led to remarkable advancements
      in emerging photovoltaics. The rapid increase in the power conversion efficiency
      (PCE) of PSCs has been mainly achieved by improving perovskite morphology and
      crystallinity. Herein, we report a simple and effective means to improve
      perovskite grain sizes using a porous hole transport layer (i.e. , PEDOT: PSS in
      this work). We used polystyrene nanospheres as a sacrificial template to
      fabricate the porous-PEDOT:PSS. The growth of the CH3NH3PbI3 perovskite film on
      the porous-PEDOT:PSS substrate yields a dramatic improvement in crystallinity and
      an enhancement in perovskite grain sizes. When the porous structure was applied
      as a hole transport layer in PSCs with planar heterojunction structures, the
      efficiency was significantly enhanced from 15.33% for the planar device to
      17.32%. This simple method for enhancing perovskite morphology and crystallinity
      paves the way for its application to other device architectures for enhanced
      photovoltaic performance.

PMID- 27883129
TI  - Platinum complexes as light promoted anticancer agents: a redefined strategy for
      controlled activation.
AB  - Site-specific delivery and amenable activation of prodrugs are indispensible
      criteria for designing novel anticancer agents. Platinum based drugs vanguard the
      chemotherapeutic regimes and over the years significant attention has been paid
      to achieve more efficacious drugs with fewer adverse effects. The switch from
      platinum(ii) drugs to the inert platinum(iv) analogues proved advantageous but
      the new prodrugs still suffered from unspecific cytotoxic actions. Thus the
      photoactivation of an inert platinum prodrug specifically within neoplastic cells
      provided the desired spatio-temporal control over drug activation by means of
      illumination, thereby limiting the cytotoxic events to only at the targeted
      tumors. This article collates research on platinum complexes which exhibit
      potential light mediated anticancer effects and provides insights into the
      underlying mechanisms of activation. Fine tuning of the coordination sphere
      results in dramatic alteration of the redox and spectral properties of both
      ground and excited states and the cellular properties of the molecules. This
      concise article highlights the various light promoted strategies employed to
      attain a controlled release of active platinum(ii) and/or reactive oxygen species
      such as photoreduction, photocaging, photodissociation and photosensitization.
      Such dual action photoactive metal complexes with improved aqueous solubility and
      versatility are promising candidates for combination therapy which is likely to
      be the future of anticancer research.

PMID- 27883128
TI  - Modeling the archetype cysteine protease reaction using dispersion corrected
      density functional methods in ONIOM-type hybrid QM/MM calculations; the
      proteolytic reaction of papain.
AB  - A proteolytic reaction of papain with a simple peptide model substrate N
      methylacetamide has been studied. Our aim was twofold: (i) we proposed a
      plausible reaction mechanism with the aid of potential energy surface scans and
      second geometrical derivatives calculated at the stationary points, and (ii) we
      investigated the applicability of the dispersion corrected density functional
      methods in comparison with the popular hybrid generalized gradient approximations
      (GGA) method (B3LYP) without such a correction in the QM/MM calculations for this
      particular problem. In the resting state of papain the ion pair and neutral forms
      of the Cys-His catalytic dyad have approximately the same energy and they are
      separated by only a small barrier. Zero point vibrational energy correction
      shifted this equilibrium slightly to the neutral form. On the other hand, the
      electrostatic solvation free energy corrections, calculated using the Poisson
      Boltzmann method for the structures sampled from molecular dynamics simulation
      trajectories, resulted in a more stable ion-pair form. All methods we applied
      predicted at least a two elementary step acylation process via a zwitterionic
      tetrahedral intermediate. Using dispersion corrected DFT methods the thioester S
      C bond formation and the proton transfer from histidine occur in the same
      elementary step, although not synchronously. The proton transfer lags behind (or
      at least does not precede) the S-C bond formation. The predicted transition state
      corresponds mainly to the S-C bond formation while the proton is still on the
      histidine Ndelta atom. In contrast, the B3LYP method using larger basis sets
      predicts a transition state in which the S-C bond is almost fully formed and the
      transition state can be mainly featured by the Ndelta(histidine) to N(amid)
      proton transfer. Considerably lower activation energy was predicted (especially
      by the B3LYP method) for the next amide bond breaking elementary step of acyl
      enzyme formation. Deacylation appeared to be a single elementary step process in
      all the methods we applied.

PMID- 27883130
TI  - Nanobubbles, cavitation, shock waves and traumatic brain injury.
AB  - Collapse of bubbles, microscopic or nanoscopic, due to their interaction with the
      impinging pressure wave produces a jet of particles moving in the direction of
      the wave. If there is a surface nearby, the high-speed jet particles hit it, and
      as a result damage to the surface is produced. This cavitation effect is well
      known and intensely studied in case of microscopic sized bubbles. It can be quite
      damaging to materials, including biological tissues, but it can also be
      beneficial when controlled, like in case of sonoporation of biological membranes
      for the purpose of drug delivery. Here we consider recent simulation work
      performed to study collapse of nanobubbles exposed to shock waves, in order to
      understand the detailed mechanism of the cavitation induced damage to soft
      materials, such as biological membranes. We also discuss the connection of the
      cavitation effect with the traumatic brain injury caused by blasts. Specifically,
      we consider possible damage to model membranes containing lipid bilayers,
      bilayers with embedded ion channel proteins like the ones found in neural cells
      and also protein assemblies found in the tight junction of the blood brain
      barrier.

PMID- 27883131
TI  - Photo-induced magnetization and first-principles calculations of a two
      dimensional cyanide-bridged Co-W bimetal assembly.
AB  - A two-dimensional cyanide-bridged Co-W bimetal assembly, (H5O2+)[Co(4
      bromopyridine)2{W(CN)8}], was prepared. A synchrotron radiation (SR) X-ray single
      crystal measurement shows that the crystal structure is monoclinic in the P21/c
      space group. Magnetic and spectroscopic measurements show that this assembly
      takes Co(S = 0)-WIV(S = 0) in the temperature range of 2-390 K. Such a wide
      temperature range Co-WIV phase has not been reported so far. First-principles
      calculations show that the band gap is composed of a WIV valence band and a CoIII
      conduction band. 785 nm light irradiation causes photo-induced magnetization with
      a Curie temperature of 27 K and a coercive field of 2000 Oe. The crystal
      structure of the photo-induced phase was determined to have larger lattice
      constants in the two-dimensional layer (bc-plane) by 3% compared to the original
      phase, which is due to the expansion of the distance of Co-N. The photo-induced
      phase returns to the original phase upon thermal treatment. First-principles
      calculations, and magnetic, and optical measurements prove that this
      photomagnetism is caused by the optical charge-transfer-induced spin transition
      from Co(S = 0)-WIV(S = 0) to Co(S = 3/2)-WV(S = 1/2).

PMID- 27883133
TI  - Na2.32Co1.84(SO4)3 as a new member of the alluaudite family of high-voltage
      sodium battery cathodes.
AB  - Electrochemical energy storage has recently seen tremendous emphasis being placed
      on the large-scale (power) grid storage. Sodium-ion batteries are capable of
      achieving this goal with economic viability. In a recent breakthrough in sodium
      ion battery research, the alluaudite framework (Na2Fe2(SO4)3) has been reported,
      with the highest Fe3+/Fe2+ redox potential (ca. 3.8 V, Barpanda, et al., Nat.
      Commun., 2014, 5, 4358). Exploring this high-voltage sodium insertion system, we
      report the discovery of Na2+2xCo2-x(SO4)3 (x = 0.16) as a new member of the
      alluaudite class of cathode. Stabilized by low-temperature solid-state synthesis
      (T <= 350  degrees C), this novel Co-based compound assumes a monoclinic
      structure with C2/c symmetry, which undergoes antiferromagnetic ordering below
      10.2 K. Isotypical to the Fe-homologue, it forms a complete family of solid
      solution Na2+2x(Fe1-yCoy)2-x(SO4)3 [y = 0-1]. Ab initio DFT analysis hints at
      potential high voltage operation at 4.76-5.76 V (vs. Na), depending on the degree
      of desodiation involving a strong participation of the oxygen sub-lattice. With
      the development of safe organic electrolytes, Na2+2xCo2-x(SO4)3 can work as a
      cathode material (~5 V) for sodium-ion batteries.

PMID- 27883132
TI  - Microfluidic PDMS on paper (POP) devices.
AB  - In this paper, we propose a generalized concept of microfluidic
      polydimethylsiloxane (PDMS) on paper (POP) devices, which combines well the
      merits of paper chips and PDMS chips. First, we optimized the conditions for
      accurate PDMS spatial patterning on paper, based on screen printing and a high
      temperature enabled superfast curing technique, which enables PDMS patterning to
      an accuracy of tens of microns in less than ten seconds. This, in turn, makes it
      available for seamless, reversible and reliable integration of the resulting
      paper layer with other PDMS channel structures. The integrated POP devices allow
      for both porous paper and smooth channels to be spatially defined on the devices,
      greatly extending the flexibility for designers to be able to construct powerful
      functional structures. To demonstrate the versatility of this design, a prototype
      POP device for the colorimetric analysis of liver function markers, serum
      protein, alkaline phosphatase (ALP) and aspartate aminotransferase (AST), was
      constructed. On this POP device, quantitative sample loading, mixing and
      multiplex analysis have all been realized.

PMID- 27883134
TI  - Non-fluorescent quantification of single mRNA with transient absorption
      microscopy.
AB  - Single molecule detection is confounded by the background signals from the
      biological environment, such as autofluorescence, Rayleigh scattering, or
      turbidity in cells and tissues. In this article, we report on the utilization of
      gold nanoparticles (AuNPs) as an orthogonal probe for non-fluorescence detection
      of single molecules with a transient absorption microscopy (TAM). The developed
      system and concepts were validated by quantitative evaluation of human epidermal
      receptor 2 (Her2) mRNA in cancer cells and tissues at single copy sensitivity.
      Results from TAM suggest that the average number of Her2 copies in SK-BR-3 and
      MCF-7 breast cancer cells is 203.19 +/- 80.48, and 11.29 +/- 4.47, respectively.
      Furthermore, TAM offers excellent signal-to-noise ratio in detecting mRNA in
      clinical tissues, indicating a significantly higher expression of Her2 genes in
      breast cancer tissues than that of normal tissues. Our single cell quantification
      TAM strategy was validated with a fluorescence in situ hybridization approach.
      Our demonstration shows that TAM has the potential to provide a new dimension in
      biomarker quantification at single molecule sensitivity in turbid biological
      environments providing a strong basis for clinical monitoring.

PMID- 27883135
TI  - Synthesis of MnO2 nanoparticles and their effective utilization as UV protectors
      for outdoor high voltage polymeric insulators used in power transmission lines.
AB  - Polymeric outdoor insulators derived from polydimethyl siloxane (PDMS) are
      replacing conventional ceramic insulators in high voltage power transmission
      lines because of their improved electrical, mechanical and hydrophobic
      performance. Major impediments like failure of polymeric insulators due to
      natural aging by UV radiation from sunlight and electrical tracking have limited
      their usage. Herein, it is demonstrated about the usage of manganese dioxide
      based nanoparticles as an effective agent to prevent the UV accelerated aging of
      polymeric insulators. MnO2 nanoparticles of different shapes and dimension were
      synthesized using a single step wet chemical reaction between KMnO4 and methyl
      acetate. Namely, 2D delta-MnO2 nanosheets, 1D alpha-MnO2 nanowires and 3D alpha
      MnO2 nanorods were formed. These nanoparticles were extensively characterized by
      various techniques. In the scope of the study, the delta-MnO2 (10-5 S cm-1; 1
      MHz) nanosheet demonstrated the lowest electrical AC conductivity and a higher
      band gap compared to the 1D (10-4 S cm-1; 1 MHz) and 3D variety (10-4 S cm-1; 1
      MHz). Owing to the lower electrical conductivity of the delta-MnO2 nanosheet, it
      was further incorporated at different filler volumes in the polymeric matrix
      (blend of polydimethyl siloxane/ethylene vinyl acetate) as a UV protector
      material for the polymer based high voltage composite polymeric insulator. The UV
      protection ability, induced by the delta-MnO2 nanosheet, was achieved without
      adversely affecting other properties of the formulated insulator compound
      material. The optimum properties of the composite were found to be obtained at 3
      phr (three parts of delta-MnO2 nanosheet per hundred parts of polymer) loading of
      the nanosheet. The current work will promise to pave a new pathway for the
      generation of UV resistant high voltage power transmission line insulator
      materials. It would be interesting in the future to study the effect of
      incorporation of manganese dioxide based nanosheets on the UV resistant
      properties of different polymeric matrices.

PMID- 27883136
TI  - Continuous micro-vortex-based nanoparticle manipulation via focused surface
      acoustic waves.
AB  - Despite increasing demand in the manipulation of nanoscale objects for next
      generation biological and industrial processes, there is a lack of methods for
      reliable separation, concentration and purification of nanoscale objects.
      Acoustic methods have proven their utility in contactless manipulation of
      microscale objects mainly relying on the acoustic radiation effect, though the
      influence of acoustic streaming has typically prevented manipulation at smaller
      length scales. In this work, however, we explicitly take advantage of the strong
      acoustic streaming in the vicinity of a highly focused, high frequency surface
      acoustic wave (SAW) beam emanating from a series of focused 6 MUm substrate
      wavelength interdigital transducers patterned on a piezoelectric lithium niobate
      substrate and actuated with a 633 MHz sinusoidal signal. This streaming field
      serves to focus fluid streamlines such that incoming particles interact with the
      acoustic field similarly regardless of their initial starting positions, and
      results in particle displacements that would not be possible with a travelling
      acoustic wave force alone. This streaming-induced manipulation of nanoscale
      particles is maximized with the formation of micro-vortices that extend the width
      of the microfluidic channel even with the imposition of a lateral flow, occurring
      when the streaming-induced flow velocities are an order of magnitude larger than
      the lateral one. We make use of this acoustic streaming to demonstrate the
      continuous and differential focusing of 100 nm, 300 nm and 500 nm particles.

PMID- 27883137
TI  - The effect of Mo doping on the charge separation dynamics and photocurrent
      performance of BiVO4 photoanodes.
AB  - Doping with electron-rich elements in BiVO4 photoanodes has been demonstrated as
      a desirable approach for improving their carrier mobility and charge separation
      efficiency. However, the effect of doping and dopant concentration on the carrier
      dynamics and photoelectrochemical performance remains unclear. In this work, we
      examined the effects of Mo doping on the charge separation dynamics and
      photocurrent performance in BiVO4 photoanodes. We show that the photocurrent of
      BiVO4 photoanodes increases with increasing concentration of the Mo dopant, which
      can be attributed to both the improved carrier mobility resulting from increased
      electron density and charge separation efficiency due to the diminishing of trap
      states upon Mo doping. The effect of doping on the electronic structure, carrier
      dynamics and photocurrent performance of BiVO4 photoanodes resulting from W and
      Mo dopants was also compared and discussed in this study. The knowledge gained
      from this work will provide important insights into the optimization of the
      carrier mobility and charge separation efficiency of BiVO4 photoanodes by
      controlling the dopants and their concentrations.

PMID- 27883138
TI  - Characterization of size-dependent mechanical properties of tip-growing cells
      using a lab-on-chip device.
AB  - Quantification of mechanical properties of tissues, living cells, and cellular
      components is crucial for the modeling of plant developmental processes such as
      mechanotransduction. Pollen tubes are tip-growing cells that provide an ideal
      system to study the mechanical properties at the single cell level. In this
      article, a lab-on-a-chip (LOC) device is developed to quantitatively measure the
      biomechanical properties of lily (Lilium longiflorum) pollen tubes. A single
      pollen tube is fixed inside the microfluidic chip at a specific orientation and
      subjected to compression by a soft membrane. By comparing the deformation of the
      pollen tube at a given external load (compressibility) and the effect of turgor
      pressure on the tube diameter (stretch ratio) with finite element modeling, its
      mechanical properties are determined. The turgor pressure and wall stiffness of
      the pollen tubes are found to decrease considerably with increasing initial
      diameter of the pollen tubes. This observation supports the hypothesis that tip
      growth is regulated by a delicate balance between turgor pressure and wall
      stiffness. The LOC device is modular and adaptable to a variety of cells that
      exhibit tip-growth, allowing for the straightforward measurement of mechanical
      properties.

PMID- 27883139
TI  - Clustered localization of EGFRvIII in glioblastoma cells as detected by high
      precision localization microscopy.
AB  - For receptor tyrosine kinases supramolecular organization on the cell membrane is
      critical for their function. Super-resolution fluorescence microscopy techniques
      have offered new opportunities for the analysis of single receptor localization.
      Here, we analysed the cluster formation of the epidermal growth factor receptor
      variant III (EGFRvIII), a deletion variant which is expressed in glioblastoma.
      The constitutively activated variant EGFRvIII is expressed in cells with an egfr
      gene amplification and is thought to enhance the tumorigenic potential especially
      of glioblastoma cells. Due to the lack of an adequate model system, it is still
      unclear how endogenous EGFRvIII expression alters cellular signalling and if it
      is organized in clusters like the wild type receptor. We have recently described
      the establishment of two pairs of iso-genetic cell lines (BS153 and DKMG),
      displaying endogenous EGFRvIII expression or not. Using these cell lines we
      investigated single receptor localization of EGFRvIII by high precision
      localization microscopy. Cluster analysis revealed that EGFRvIII is present in
      clusters on the surface of the cells, with about 60% or even more receptor
      molecules being assembled in clusters of approximately 100 nm in diameter whereby
      the cluster definition was iteratively determined. The signal to signal distance
      may indicate dimer formation while signal quantification indicates 1 * 106-5 *
      106 EGFRvIII molecules per cell. Altogether, these data give unique insights into
      the membrane surface localization of EGFRvIII in glioblastoma cells. These
      insights will help to unveil the function of this tumour associated receptor
      variant which might lead to a better understanding of glioblastoma and therefore
      could lead to improved therapy approaches.

PMID- 27883141
TI  - Asymmetric cycloaddition reactions catalysed by diarylprolinol silyl ethers.
AB  - Cycloaddition reactions are among the most important tools for the construction
      of cyclic compounds in organic synthesis, since these reactions are vital to
      access natural products and biologically active compounds. Organocatalysis plays
      an increasingly pivotal role in these reactions, often allowing several
      stereocenters to be selectively created and integrated in the target molecule.
      Among the large number of efficient types of organocatalysts available, the
      diarylprolinol silyl ethers have been established as one of the most frequently
      used in aminocatalysis allowing for novel activation modes and reaction concepts.
      In this review, we will focus on the different activation modes made available by
      the diarylprolinol silyl ether system with the aim of highlighting their
      applicability in asymmetric cycloadditions for the assembly of complex molecular
      architectures.

PMID- 27883142
TI  - A scalable in situ surfactant-free synthesis of a uniform MnO/graphene composite
      for highly reversible lithium storage.
AB  - A novel MnO/graphene composite, used as an anode for lithium ion intercalation,
      was prepared via an in situ surfactant-free facile method by taking advantage of
      the byproduct Mn ion in the conventional fabrication of graphene oxide. The as
      fabricated lithium ion batteries exhibited a long-term stable reversible capacity
      (603 mA h g-1 after 350 cycles at 1 A g-1 based on the composite, hereinafter the
      same) and superior rate performance (400 mA h g-1 at 3 A g-1).

PMID- 27883143
TI  - The role of stoichiometry in superconducting Nb1-betaSnbeta: electronic and
      vibrational properties from ab initio calculations.
AB  - Using first principles calculations based on density functional theory, the
      electronic, vibrational and superconducting properties of compounds with
      different stoichiometry ratios in the A15 phase have been studied. To this
      purpose, the lambda mass enhancement parameter, which determines the
      superconducting critical temperature through the Allen-Dynes modification of the
      McMillan formula, has been explicitly calculated in the context of the density
      functional perturbation theory that allows the calculation of the matrix elements
      of the electron-phonon interactions at different compositions related to the Sn
      content. Our results provide a better understanding of the inhomogeneous
      composition of one of the most widely employed low-temperature superconductors,
      evidencing the electronic properties and the phonon modes that are responsible
      for the critical temperature degradation as the Sn concentration is varied.

PMID- 27883144
TI  - Robust synthesis of F-BODIPYs.
AB  - A protocol is established for the high-yielding synthesis of F-BODIPYs involving
      non-anhydrous reagents and not requiring precautions to exclude moisture. This
      simple and robust strategy simply requires a second addition of NEt3 and
      BF3.OEt2, midway through the reaction period. The ratio and amounts of NEt3 and
      BF3.OEt2 used in each aliquot are critical to success (6 : 9 for each aliquot).
      The protocol can be completed using bench-dry apparatus, without need to achieve
      and maintain anhydrous conditions or solvents.

PMID- 27883140
TI  - Single-molecule fluorescence resonance energy transfer in molecular biology.
AB  - Single-molecule fluorescence resonance energy transfer (smFRET) is a powerful
      technique for studying the conformation dynamics and interactions of individual
      biomolecules. In this review, we describe the concept and principle of smFRET,
      illustrate general instrumentation and microscopy settings for experiments, and
      discuss the methods and algorithms for data analysis. Subsequently, we review
      applications of smFRET in protein conformational changes, ion channel open-close
      properties, receptor-ligand interactions, nucleic acid structure regulation,
      vesicle fusion, and force induced conformational dynamics. Finally, we discuss
      the main limitations of smFRET in molecular biology.

PMID- 27883146
TI  - Tunable doping of graphene by using physisorbed self-assembled networks.
AB  - One current key challenge in graphene research is to tune its charge carrier
      concentration, i.e., p- and n-type doping of graphene. An attractive approach in
      this respect is offered by controlled doping via well-ordered self-assembled
      networks physisorbed on the graphene surface. We report on tunable n-type doping
      of graphene using self-assembled networks of alkyl-amines that have varying chain
      lengths. The doping magnitude is modulated by controlling the density of the
      strong n-type doping amine groups on the surface. As revealed by scanning
      tunneling and atomic force microscopy, this density is governed by the length of
      the alkyl chain which acts as a spacer within the self-assembled network. The
      modulation of the doping magnitude depending on the chain length was demonstrated
      using Raman spectroscopy and electrical measurements on graphene field effect
      devices. This supramolecular functionalization approach offers new possibilities
      for controlling the properties of graphene and other two-dimensional materials at
      the nanoscale.

PMID- 27883148
TI  - Dual-affinity peptide mediated inter-protein recognition.
AB  - We present for the first time an enhanced interaction affinity between an
      abundant soluble protein (human serum albumin) and a membrane protein (chemokine
      receptor 4) mediated by a dual-affinity peptide E5.

PMID- 27883150
TI  - Metal-free radical thiolations mediated by very weak bases.
AB  - Aromatic thioethers and analogous heavier chalcogenides were prepared by reaction
      of arene-diazonium salts with disulfides in the presence of the cheap and weak
      base NaOAc. The mild and practical reaction conditions (equimolar reagents, DMSO,
      r.t., 8 h) tolerate various functional groups (e.g. Br, Cl, NO2, CO2R, OH, SCF3,
      furans). Mechanistic studies indicate the operation of a radical aromatic
      substitution mechanism via aryl, acetyloxyl, thiyl, and dimsyl radicals.

PMID- 27883152
TI  - A resettable and reprogrammable biomolecular keypad lock with dual outputs based
      on glucose oxidase-Au nanoclusters-Prussian blue nanocomposite films on an
      electrode surface.
AB  - In this work, electrochromic Prussian blue (PB) films were electrodeposited on
      the surface of indium tin oxide (ITO) electrodes, and a dispersion mixture of
      glucose oxidase (GOD), chitosan (CS) and gold nanoclusters (AuNCs) was then cast
      on the PB surface to form CS-AuNC-GOD/PB nanocomposite film electrodes. The blue
      PB component in the films could be changed into its colourless reduced form of
      Prussian white (PW) upon application of -0.2 V. The addition of glucose to the
      solution would produce H2O2 with the help of GOD in the films and oxygen in the
      solution, which could oxidize PW back to PB. In the meantime, the fluorescence
      emission signal of the AuNCs in the films was greatly influenced by the form of
      PB/PW. Based on these properties, the amperometric current, fluorescence
      intensity and UV-vis absorbance of the film electrodes demonstrated potential-
      and glucose-sensitive ON-OFF behaviors. Thus, a 2-input/3-output biomolecular
      logic gate system with 3 different types of output signals and a 2-to-1 encoder
      were developed. Furthermore, a resettable and reprogrammable 3-input biomolecular
      keypad lock was established with fluorescence intensity and UV-vis absorbance as
      dual outputs, which greatly enhanced the security level of the keypad lock. This
      work reported for the first time an enzyme-based keypad lock with dual outputs,
      which might open a new avenue to design more complicated biomolecular keypad lock
      systems.

PMID- 27883153
TI  - Organocatalyzed asymmetric Michael addition by an efficient bifunctional
      carbohydrate-thiourea hybrid with mechanistic DFT analysis.
AB  - A series of thiourea based bifunctional organocatalysts having d-glucose as a
      core scaffold were synthesized and examined as catalysts for the asymmetric
      Michael addition reaction of aryl/alkyl trans-beta-nitrostyrenes over
      cyclohexanone and other Michael donors having active methylene. Excellent
      enantioselectivities (<95%), diastereoselectivities (<99%), and yields (<99%)
      were attained under solvent free conditions using 10 mol% of 1d0. The obtained
      results were explained through DFT calculations using the B3LYP/6
      311G(d,p)//B3LYP/6-31G(d) basic set. The QM/MM calculations revealed the role of
      cyclohexanone as a solvent as well as reactant in the rate determining step
      imparting 31.91 kcal mol-1 of energy towards the product formation.

PMID- 27883154
TI  - The effect of the nanofibrous Al2O3 aspect ratio on Fischer-Tropsch synthesis
      over cobalt catalysts.
AB  - A series of nanofibrous alumina materials with diameters of 4-6 nm and with
      different aspect ratios ranging from 3 to 16 were prepared. Cobalt impregnated
      catalysts were prepared by means of incipient wetness impregnation on alumina
      nanofibers while the 'rearranged' catalysts were prepared by using
      ultrasonication assistance to mix the fibers with the Co3O4 nanoparticles. The
      effects of the alumina nanofiber aspect ratios on the Co catalyst structure and
      performance for Fischer-Tropsch synthesis were studied. The pore size of the two
      series of catalysts increased as the aspect ratio of the alumina nanofiber
      increased. For impregnated catalysts, large Co3O4 particles were formed on the
      external surface of the alumina support when the aspect ratio was 3 and 5, while
      the crystallite sizes of Co3O4 increased from 13.3 nm to 15.6 nm with the
      increase of the aspect ratio from 7 to 16. The four 'rearranged' catalysts
      possessed similar and homogeneously dispersed Co3O4 crystallites of 9.5 nm. As
      expected the reduction behavior of the two series of catalysts was primarily
      influenced by the Co3O4 crystallite size and structure. The FT data of the two
      series of catalysts indicate that dispersed Co catalysts on alumina nanofibers
      with large aspect ratios having large inter-crystallite pores significantly
      improve the catalyst activity and C5+ selectivity. The FT data of the
      'rearranged' catalysts strongly demonstrated that the internal mass transfer of
      reactants and products increased with a decrease in inter-crystallite pore size,
      resulting in a decrease of C5+ selectivity and C3 olefin/paraffin ratio, and an
      increase of CH4 selectively, while the CO consumption rate was little altered.
      Furthermore, catalytic stability tests showed that the alumina nanofibers with
      larger aspect ratios inhibited Co migration and coalescence in the matrices of
      the nanofibrous alumina, and this significantly enhanced the stability of the
      catalyst. The Cop/Al2O3-16 catalyst possessing uniformly distributed cobalt,
      improved reducibility and large pores is the preferred choice to generate high
      catalytic activity, stability and C5+ selectivity.

PMID- 27883155
TI  - In situ integration of CoFe alloy nanoparticles with nitrogen-doped carbon
      nanotubes as advanced bifunctional cathode catalysts for Zn-air batteries.
AB  - Electrochemical catalysis of O2-incorporated reactions is a promising strategy
      for metal-air batteries. The performance of metal-air batteries is determined by
      the catalytic activities of the oxygen reduction reaction (ORR) and oxygen
      evolution reaction (OER). Therefore, developing efficient catalysts with superior
      activities for the ORR and OER is of great significance to expand the application
      range of metal-air batteries. Herein, CoFe alloy nanoparticles adhered to the
      inside wall of nitrogen doped carbon nanotubes (CoFe@NCNTs) are synthesized and
      can function as a Janus particle to efficiently catalyze the ORR and OER with
      desirable activities in 0.1 M KOH solution. Specifically, the CoFe@NCNTs present
      an onset potential of 0.95 V and a half-wave potential of 0.84 V as an ORR
      catalyst. When used as an air-cathode catalyst for a Zn-air battery, the
      CoFe@NCNTs cathode performs better than a Pt/C cathode, showing a high open
      circuit potential of 1.45 V, a maximum power density of 150 mW cm-2 and an
      average specific capacity of 808 mA h gzn-1 at current densities from 2 mA cm-2
      to 10 mA cm-2.

PMID- 27883156
TI  - Synthesis of the biological repeating unit of Streptococcus pneumoniae serotype
      23F capsular polysaccharide.
AB  - An efficient synthesis of the 3-aminopropyl glycoside of the biological repeating
      unit of Streptococcus pneumoniae serotype 23F capsular polysaccharide (CPS) was
      accomplished. The synthetic target contained a tetrasaccharide with a
      phosphoglycerol branch. Its oligosaccharide backbone was assembled via linear
      glycosylation, and the challenging beta-rhamnosyl linkage in its structure was
      achieved stereospecifically through naphthylmethyl-assisted intramolecular
      aglycon delivery (IAD). The remaining 1,2-trans glycosylation reactions were
      executed in excellent yields and stereoselectivity based on neighboring group
      participation. The phosphoglycerol branch was installed by the phosphoramidite
      method with benzylidene-protected glycerol 2-phosphoramidite as the substrate.
      Eventually, the target molecule was synthesized from monosaccharide building
      blocks in 17 longest linear steps and a 3.85% overall yield. In addition, the
      synthetic target also contained a free amino group at its reducing end,
      facilitating its conjugation with other molecules for various biological studies
      and applications.

PMID- 27883158
TI  - Fast or slow-foods? Describing natural variations in oral processing
      characteristics across a wide range of Asian foods.
AB  - The structural properties of foods have a functional role to play in oral
      processing behaviours and sensory perception, and also impact on meal size and
      the experience of fullness. This study adopted a new approach by using
      behavioural coding analysis of eating behaviours to explore how a range of food
      textures manifest as the microstructural properties of eating and expectations of
      fullness. A selection of 47 Asian foods were served in fixed quantities to a
      panel of participants (N = 12) and their eating behaviours were captured via web
      camera recordings. Behavioural coding analysis was completed on the recordings to
      extract total bites, chews and swallows and cumulative time of the food spent in
      the mouth. From these measurements a series of microstructural properties
      including average bite size (g), chews per bite, oro-sensory exposure time
      (seconds) and average eating rate (g min-1) were derived per food. The sensory
      and macronutrient properties of each food were correlated with the microstructure
      of eating to compare the differences in eating behaviour on a gram for gram
      basis. There were strong relationships between the perceived food textural
      properties and its eating behaviours and a food's total water content was the
      best predictor of its eating rate. Foods that were eaten at a slower eating rate,
      with smaller bites and more chews per bite were rated as higher in the expected
      fullness. These relationships are important as oral processing behaviours and
      beliefs about the potential satiating value of food influence portion decisions
      and moderate meal size. These data support the idea that naturally occurring
      differences in the food structure and texture could be used to design meals that
      slow the rate of eating and maximise fullness.

PMID- 27883159
TI  - Melatonin and hydroxytyrosol-rich wines influence the generation of DNA oxidation
      catabolites linked to mutagenesis after the ingestion of three types of wine by
      healthy volunteers.
AB  - The Mediterranean Diet (MD) has been proved to exert benefits with respect to the
      maintenance of the redox balance, and wine is a representative component.
      Bioactive compounds such as polyphenols, melatonin and hydroxytyrosol act as
      radical scavengers and regulate the oxidation status of organisms. Oxidative
      damage to DNA yields a large range of end products. The repair of oxidized DNA
      entails the removal of the useless bases and/or nucleotides as well as the
      release of circulating nucleotides and nucleosides. The current research aims to
      elucidate, for the first time, the DNA protection against oxidative stress
      provided by three types of red wine - relating it to the intake of bioactive
      compounds - after the intake of a serving of red wine/must by 18 healthy female
      volunteers during a short term double-blind, crossover and placebo-controlled
      study. The novelty of our work is to describe the importance of melatonin and
      hydroxytyrosol and its metabolites (from gut microflora) in comparison with
      polyphenols in a red wine matrix (excluding colon derivatives). The results show
      that the intake of red wine and must secondarily reduces oxidative stress and
      carcinogenesis due to their content of homovanillic acid, as measured by
      decreases in the plasmatic concentration of 8-hydroxy-2'deoxyguanosine, 8
      hydroxyguanine, and 8-nitroguanosine. Moreover, the intake of wine appears to
      exert vasodilatory effects, mediated by the action of nitric oxide and increased
      plasma guanosine-3'-5'-cyclic monophosphate plasmatic levels, owing to the intake
      of wines higher in melatonin and homovanillic acid. Therefore, the results
      obtained in the present study revealed that polyphenols, despite being the major
      compounds in the red wine matrix, are not the most effective compounds protecting
      DNA from oxidative attack.

PMID- 27883160
TI  - Highly-repeatable generation of very small nanoparticles by pulsed-laser ablation
      in liquids of a high-speed rotating target.
AB  - By irradiating a cylindrical silver target rotated at a high-speed within the
      range 300-2400 rpm (lateral speed 0.16-1.25 m s-1) in pure water, we prepare
      ligand-free Ag nanoparticles (NPs) with a size of 4 +/- 2 nm which are likely to
      be primary particles. Usually, the generation of NPs showing such a small size
      requires either a laser post-treatment and/or chemical additives. As the rotation
      rate of the target is increased, calculated 3D flow patterns revealed different
      hydrodynamic regimes which clearly influence the ablation rate and repeatability
      of the process as well as the colloidal properties. In addition to revealing the
      importance of fluid dynamics in pulsed-laser ablations in liquids, this study
      provides a way for producing in one step pure NPs with sizes below 5 nm which are
      suitable for applications in catalysis.

PMID- 27883161
TI  - [Is it necessary to prescribe antibiotics in impacted third molar surgical
      removal?: comparative study between prescribing patterns].
AB  - OBJECTIVE: To assess whether there is a significant difference in infection rate
      after surgery tooth extraction in two different hospitals from Norway and Spain
      where different surgical antimicrobial prophylaxis protocols are applied.
      METHODS: An analytical observational study was conducted, retrospective cohorts
      type, analyzing healthy patients with no risk factors, who were third molar tooth
      operated in maxillofacial services of two different hospitals: St. Olav in
      Trondheim (Norway) and Clinico San Carlos in Madrid (Spain). The collected
      variables were: age, number of tooth removed, anesthesia type, and observations
      about the course of the operation registered in the clinical history. To assess
      the development of postoperative infection, patient's data of those who chose the
      hospital as the place to remove the suture thread were collected in Norway,
      whereas in Spain a telephone survey was conducted to determine the course of the
      operation months later. RESULTS: In St. Olav Hospital 11.1% of patients operated
      received antibiotic regimen after surgery, while in Hospital San Carlos were
      100%. The infection rate was 15% in St.Olav Hospital and 7.5% in Hospital San
      Carlos. These differences were no statistically significant. CONCLUSIONS: The
      routine administration of antibiotics to healthy patients with no risk factors
      undergoing impacted third molar surgical removal is a common clinical practice
      which it does not seem to be justified.

PMID- 27883162
TI  - Late aortic silver graft re-infection due to Streptococcus milleri group
      (Streptococcus anginosus). Case report and literature review.

PMID- 27883163
TI  - [First clinical isolate of Mycobacterium tuberculosis exhibiting resistance to
      rifampicin and sensibility to isoniazid in the Elche's Health Department-General
      Hospital(1998-2015)].

PMID- 27883165
TI  - "Move on Against Frailty": Time to Raise Awareness about Frailty and Prevention
      of Disability in the Community.

PMID- 27883164
TI  - Sarcopenia Trials in Specific Diseases: Report by the International Conference on
      Frailty and Sarcopenia Research Task Force.
AB  - Muscle atrophy occurs as a consequence of a number of conditions, including
      cancer, chronic obstructive pulmonary disease (COPD), diabetes mellitus, heart
      failure, and other chronic diseases, where it is generally a predictor of poor
      survival. It also occurs as a consequence of disuse and an age-related loss of
      muscle mass and strength (sarcopenia). The aims of the 2016, International
      Conference on Frailty and Sarcopenia Research (ICFSR) Task Force were to examine
      how these specific chronic conditions have been employed in treatment trials thus
      far and how future trials using these patient groups might be designed for
      efficient identification of effective sarcopenia interventions. Functional
      limitations assessed as gait speed, distance walked over a set time period, or
      other attributes of physical performance have been suggested as outcome measures
      in sarcopenia trials. Indeed, such measures have already been used successfully
      in a number of trials aimed at preventing disability in older adults.

PMID- 27883167
TI  - Frailty Is a Geriatric Syndrome Characterized by Multiple Impairments: A
      Comprehensive Approach Is Needed.
AB  - OBJECTIVE: To evaluate the prevalence of frailty and the associated
      multimorbidity and functional impairments among community-dwelling middle-aged
      and elderly people in Taiwan. DESIGN: a cross-sectional study. SETTING:
      communities in I-Lan County of Taiwan. PARTICIPANTS: 1839 community-dwelling
      people aged 50 years and older. INTERVENTION: None. MEASUREMENTS: Frailty defined
      by Fried's criteria, Charlson's comorbidity index (CCI), Functional Autonomy
      Measurement System (SMAF), Center for Epidemiologic Studies Depression Scale (CES
      D), Mini-Nutrition Assessment (MNA), Mini-Mental State Examination (MMSE), and
      Short Form-12 quality of life questionnaire. RESULTS: Overall, 1839 subjects
      (mean age: 63.9+/-9.3 years, 47.5% males) participated in this study and men were
      more likely to have higher educational level, more smoking and alcohol drinking
      habit. The prevalence of frailty was 6.8% in this study, while pre-frailty was
      40.5% and 53.7% of all participants were robust. Compared to subjects with
      different frailty status, age, education year, alcohol drinking, hypertension,
      diabetes mellitus, hyperlipidemia, CCI, walking speed, handgrip strength, score
      of SMAF, CES-D, MNA, MMSE, quality of life were significantly different between
      groups (P all< 0.05). Older age, poorer physical function, poorer cognitive
      function, poorer nutritional status, more depressive symptoms, higher CCI and
      poorer quality of life were all independently associated with frailty.
      CONCLUSIONS: Frailty was not simply a geriatric syndrome, but the combination of
      multiple geriatric syndromes. Further study is needed to evaluate the clinical
      benefits of intervention programs for community-dwelling middle-aged and older
      people to reverse frailty and its associated functional impairments.

PMID- 27883166
TI  - Effect of Low-Dose Rapamycin on Senescence Markers and Physical Functioning in
      Older Adults with Coronary Artery Disease: Results of a Pilot Study.
AB  - Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence
      associated secretory phenotype (SASP). We studied the safety and feasibility of
      low-dose rapamycin and its effect on SASP and frailty in elderly undergoing
      cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient
      received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median
      age was 73.9+/-7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs
      4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased. Adipose tissue expression of
      mRNAs (arbitrary units) for MCP-1 (3585 vs 2020, p=0.06), PPAR-gamma (1257 vs
      1166), PAI-1 (823 vs 338, p=0.08) increased, whereas interleukin-8 (163 vs 312),
      TNF-alpha (75 vs 94) and p16 (129 vs 169) decreased. Cellular senescence
      associated beta galactosidase activity (2.2% vs 3.6%, p=0.18) tended to decrease.
      We observed some correlation between some senescence markers and physical
      performance but no improvement in frailty with rapamycin was noted.
      (NCT01649960).

PMID- 27883168
TI  - Exercise Interventions for Preserving Physical Function Among Cancer Survivors in
      Middle to Late Life.
AB  - The purpose of this review was to evaluate randomized controlled trials aiming to
      preserve the functional status, i.e. physical capabilities, of middle-aged and
      older cancer survivors through a structured, physical exercise intervention. The
      study team performed a thorough search of the literature using six online
      databases. This literature search limited included studies to randomized
      controlled trials which implemented a structured physical activity intervention
      for middle- and older-aged adults diagnosed with cancer. Studies were also
      required include at least one objective measure of physical function as a
      dependent outcome. This literature search yielded thirty-eight studies. The
      majority of the literature reviewed was successful in improving several
      functional outcomes including time needed to rise from a chair or distance
      covered during the six-minute walk test. A large number of published trials also
      suggest that exercise is effective in decreasing fatigue. However, a lack of
      trials investigating outcomes in older populations (>= 65 years) was noted in
      this review. The results of this review suggest that a structured exercise
      program may be physically beneficial for middle-aged to older cancer survivors.
      Particularly, such interventions could preserve the functional status of cancer
      patients and, consequently, improve their long-term health outcomes. Future
      implications include further investigation into strictly older cancer patient
      populations, as outcomes related to exercise might differ between older and
      middle-aged adults.

PMID- 27883169
TI  - Association between Continuous Wearable Activity Monitoring and Self-Reported
      Functioning in Assisted Living Facility and Nursing Home Residents.
AB  - BACKGROUND: Physical functioning is a key factor in independent living, and its
      preclinical state assessment and monitoring during the subject's normal life
      would be beneficial. OBJECTIVES: The aim of the study is to analyse associations
      between ambulatory measured physical activity behaviour and sleep patterns (wrist
      actigraphy) and self-reported difficulties in performing activities of daily
      living. Participants, setting and design: 36 residents in assisted living
      facilities and nursing homes (average age=80.4+/-9.0 years) without dementia in
      free living conditions participated. Actigraphic monitoring is integrated with
      the facilities' social alarm system. MEASUREMENTS: Indices on activity level,
      activity rhythm, sleep pattern and external stimuli response of sleep-wake
      behaviours were extracted from the actigraph data and correlated (Spearman rank
      order correlation) with activities of daily living measures. Bonferroni
      correction for multiple comparisons was applied. RESULTS: Activity level (rho=
      0.49, p<0.05) and night-time activity variance (rho=-0.69, p<0.01) had
      correlation with the activities of daily living scores. The similarity of subject
      wise activity pattern to facility common activities had a trend with activities
      of daily living (rho=-0.44, p<0.1). In longitudinal case analysis, sleep and
      activity patterns were found to be associated with local weather variables.
      CONCLUSIONS: Activity patterns as measured by actigraphy may provide objective
      information on older people's behaviour related to functioning state and its
      changes in nursing home and assisted living facility settings. However, variance
      between individuals was large in this dataset which decreases the reliability of
      the results. Furthermore, external stimuli such as weather and facility-related
      activities can affect subjects' activity and sleep behaviour and should be
      considered in the related studies as well.

PMID- 27883171
TI  - Frailty in Postmenopausal African American and Hispanic HIV-Infected Women.
AB  - Studies suggest frailty occurs earlier in HIV-infected individuals, but data in
      postmenopausal HIV-infected women are lacking. We assessed the prevalence of
      frailty and association with anthropometric measures in HIV-infected and
      uninfected postmenopausal women. Fried's frailty phenotype was measured in HIV
      infected and uninfected Hispanic and African American postmenopausal women
      participating in a study of bone metabolism; fat and lean mass were measured by
      whole body dual energy x-ray absorptiometry (DXA). Multivariable logistic
      regression evaluated frailty risk factors. The study was conducted at Columbia
      University Medical Center between 2002 and 2007. The participants were 61 HIV
      infected and 27 uninfected Hispanic and African American postmenopausal women.
      The study compared prevalence and predictors of frailty in HIV-infected and
      uninfected postmenopausal women. Prevalence of frailty tended to be higher among
      HIV-infected than uninfected controls (11.5% vs 0% p=0.07). Surprisingly, among
      HIV-infected women, total body fat, not lean mass, was associated with frailty in
      multivariate analysis. Higher prevalence of frailty in African American and
      Hispanic HIV-infected postmenopausal women (11.5%) was similar to the 11%
      prevalence reported in minority women who were 10 years older in the general
      population. Our data suggest that frailty occurs earlier in HIV-infected
      postmenopausal women, but larger longitudinal studies are necessary to confirm
      whether musculoskeletal aging is accelerated by HIV infection.

PMID- 27883172
TI  - Can an Intervention with Testosterone and Nutritional Supplement Improve the
      Frailty Level of Under-Nourished Older People?
AB  - OBJECTIVE: To examine whether a testosterone and a high calorie nutritional
      supplement intervention can reduce frailty scores in undernourished older people
      using multiple frailty tools. DESIGN: Randomized controlled trial.
      SETTING/PARTICIPANTS: 53 community-dwelling, undernourished men and women aged
      >65 years from South Australia, Victoria and New South Wales. INTERVENTION:
      Intervention group received oral testosterone undecanoate and a high calorie
      supplement (2108-2416 kJ/day) whereas the control group received placebo
      testosterone and low calorie supplement (142-191 kJ/day). MEASUREMENTS: Frailty
      was operationalized using three frailty indices (FI-lab, FI-self-report, FI
      combined) and the frailty phenotype. RESULTS: There were no significant
      differences in changes in frailty scores at either 6 or 12 months follow up
      between the two treatment groups for all scales. Participants at the intervention
      group were 4.8 times more likely to improve their FI-combined score at both time
      points compared to the placebo group. CONCLUSION: A testosterone and a high
      calorie nutritional supplement intervention did not improve the frailty levels of
      under-nourished older people. Even so, when frailty was measured using a frailty
      index combining self-reported and lab data we found that participants who
      received the intervention were more likely to show persistent improvement in
      their frailty scores.

PMID- 27883173
TI  - Clinical application of SNP array analysis in first-trimester pregnancy loss: a
      prospective study.
AB  - Chromosomal microarray analysis (CMA) has been used routinely in pediatric and
      prenatal genetic diagnosis in clinical practice, but it has rarely been applied
      to miscarriage analysis. In this study, we conducted a prospective study to
      evaluate the feasibility of CMA for genetic diagnosis of first-trimester
      miscarriage specimens. We successfully analyzed 551 fresh miscarriage specimens
      using single-nucleotide polymorphism (SNP) array. Among the specimens, 2.9%
      (16/551) had significant maternal cell contamination and were excluded from the
      study. Clinically significant chromosomal abnormalities were identified in 295
      (55.1%) cases, including 214 (40%) with aneuploidy, 40 (7.5%) with polyploidy, 19
      (3.6%) with partial aneuploidy, 12 (2.2%) with pathogenic
      microdeletion/microduplication, and 10 (1.9%) with uniparental isodisomy
      (isoUPD). Variants of uncertain significance were obtained in 15 cases (2.8%).
      Notably, isoUPD involving a single chromosome (chromosome 22) and two recurrent
      copy number variations, 22q11.2 microdeletion and 7q11.23 microdeletion, were
      identified as probably to be associated with miscarriage. The frequency and
      distribution of genetic aberrations in the spontaneous abortion group was not
      significantly different from those in the recurrent miscarriage group. Our study
      suggests SNP array is a reliable, robust, and high-resolution technology for
      genetic diagnosis of miscarriage in clinical practice.

PMID- 27883174
TI  - Maximization of cell viability rather than biocatalyst activity improves whole
      cell omega-oxyfunctionalization performance.
AB  - It is a common misconception in whole-cell biocatalysis to refer to an enzyme as
      the biocatalyst, thereby neglecting the structural and metabolic framework
      provided by the cell. Here, the low whole-cell biocatalyst stability, that is,
      the stability of specific biocatalyst activity, in a process for the terminal
      oxyfunctionalization of renewable fatty acid methyl esters was investigated. This
      reaction, which is difficult to achieve by chemical means, is catalyzed by
      Escherichia coli featuring the monooxygenase system AlkBGT and the uptake
      facilitator AlkL from Pseudomonas putida GPo1. Corresponding products, that is,
      terminal alcohols, aldehydes, and acids, constitute versatile bifunctional
      building blocks, which are of special interest for polymer synthesis. It could
      clearly be shown that extensive dodecanoic acid methyl ester uptake mediated by
      high AlkL levels leads to whole-cell biocatalyst toxification. Thus, cell
      viability constitutes the primary factor limiting biocatalyst stability and, as a
      result, process durability. Hence, a compromise had to be found between low
      biocatalyst activity due to restricted substrate uptake and poor biocatalyst
      stability due to AlkL-mediated toxification. This was achieved by the fine-tuning
      of heterologous alkL expression, which, furthermore, enabled the identification
      of the alkBGT expression level as another critical factor determining biocatalyst
      stability. Controlled synthesis of AlkL and reduced alkBGT expression finally
      enabled an increase of product titers by a factor of 4.3 up to 229 g Lorg-1 in a
      two-liquid phase bioprocess setup. Clearly, omega-oxyfunctionalization process
      performance was determined by cell viability and thus biocatalyst stability
      rather than the maximally achievable specific biocatalyst activity. Biotechnol.
      Bioeng. 2017;114: 874-884. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883175
TI  - Heads you win, tails you lose: filtration processing for the microscopical
      examination of sperm heads.
AB  - The sperm head plays a key role in many fertilisation events and determining the
      precise location of molecules within the head region is important in
      mechanistically dissecting the fertilisation process. Such molecules may be
      present in low copy number and many sperm head profiles must be examined to
      localise them to particular subcellular structures with confidence. Filtration
      has traditionally been used for the purpose of concentrating biological material,
      such as free-living cells, spores, and subcellular fractions, and little attempt
      has been made to extend the procedure to encompass the entire processing
      schedule, mainly due to the incompatibility of intermediate dehydrating solvents
      with membrane filters. The novel and simple technique of filtration processing
      that we describe produced a dense mat of cells, with several sperm heads being
      visible in coronal orientation in a high-power field at the light microscopic
      level, and allowed positive immunocytochemical staining to be identified with
      confidence. This new technique exploits the low viscosity of LR White acrylic
      resin to allow the entire processing procedure to be undertaken in the filtration
      apparatus. In contrast, conventional techniques for preparing free-living cells,
      namely pre-embedding in a supportive matrix prior to processing, and
      centrifugation at each stage of the processing procedure, proved suboptimal,
      partly due to the final concentration that could be achieved, but mainly due to
      the random orientation of cells that these techniques afforded.

PMID- 27883170
TI  - MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc
      Roussillon): A Success Story of the European Innovation Partnership on Active and
      Healthy Ageing.
AB  - The Region Languedoc Roussillon is the umbrella organisation for an
      interconnected and integrated project on active and healthy ageing (AHA). It
      covers the 3 pillars of the European Innovation Partnership on Active and Healthy
      Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C)
      and (D) Active and independent living of elderly people. All sub-activities (poly
      pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory
      diseases, chronic diseases with multimorbidities, chronic infectious diseases,
      active and independent living and disability) have been included in MACVIA-LR
      which has a strong political commitment and involves all stakeholders (public,
      private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster.
      It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the
      vision that the prevention and management of chronic diseases is essential for
      the promotion of AHA and for the reduction of handicap. The main objectives of
      MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs
      in order to reduce avoidable hospitalisations and loss of autonomy while
      improving quality of life, (ii) to disseminate the innovation. The three years of
      MACVIA-LR activities are reported in this paper.

PMID- 27883176
TI  - miR-429 is involved in regulation of NF-kappaBactivity by targeting IKKbeta and
      suppresses oncogenic activity in cervical cancer cells.
AB  - Dysregulation of microRNAs (miRNAs) can contribute to tumorigenesis in cancers.
      In this study, we found that miR-429 was downregulated in cervical cancer (CC)
      tissues and suppressed cell viability and proliferation while promoting apoptosis
      in CC cells. IKKbeta was a novel target gene of miR-429 and ectopic expression of
      IKKbeta abrogated the phenotypes induced by miR-429. When IKKbeta was
      downregulated by miR-429, nuclear factor kappaB (NF-kappaB) pathway activation,
      interleukin-6 (IL-6), and interferon-beta (IFN-beta) production were decreased in
      CC cells. These findings indicate that miR-429 is involved in regulation of the
      NF-kappaB pathway by targeting IKKbeta and functions as a tumor suppressor in
      cervical carcinogenesis.

PMID- 27883177
TI  - Feasibility of clinical detection of cervical dysplasia using angle-resolved low
      coherence interferometry measurements of depth-resolved nuclear morphology.
AB  - This study sought to establish the feasibility of using in situ depth-resolved
      nuclear morphology measurements for detection of cervical dysplasia. Forty
      enrolled patients received routine cervical colposcopy with angle-resolved low
      coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans
      from 63 tissue sites were compared to histopathological analysis of co-registered
      biopsy specimens which were classified as benign, low-grade squamous
      intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion
      (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic
      and HSIL versus LSIL/benign to determine both accuracy and potential clinical
      utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was
      conducted using both traditional Mie theory based processing and a new hybrid
      algorithm that provides improved processing speed to ascertain the feasibility of
      real-time measurements. Analysis of depth-resolved nuclear morphology data
      revealed a/LCI was able to detect a significant increase in the nuclear diameter
      at the depth bin containing the basal layer of the epithelium for dysplastic
      versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001).
      Both processing techniques resulted in high sensitivity and specificity (>0.80)
      in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a
      threefold decrease in processing time at a slight cost in classification
      accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive
      clinical tool for detecting cervical dysplasia and guiding the identification of
      optimal biopsy sites. The faster speed from the hybrid algorithm offers a
      promising approach for real-time clinical analysis.

PMID- 27883178
TI  - Genotype-phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients
      with mucopolysaccharidosis type II.
AB  - Mucopolysaccharidosis type II (Hunter syndrome, MPS II, OMIM 309900) is an X
      linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase
      (IDS). We analyzed clinical and laboratory data from 44 Slavic patients with this
      disease. In total, 21 Czech, 7 Slovak, 9 Croatian and 7 Serbian patients (43 M/1
      F) were included in the study (median age 11.0 years, range 1.2-43 years). Birth
      prevalence ranged from 1:69,223 (Serbia) to 1:192,626 (Czech Rep.). In the
      majority of patients (71%), the disease manifested in infancy. Cognitive
      functions were normal in 10 patients. Four, six and 24 patients had mild,
      moderate, and severe developmental delay, respectively, typically subsequent to
      developmental regression (59%). Residual enzyme activity showed no predictive
      value, and estimation of glycosaminoglycans (GAGs) had only limited importance
      for prognosis. Mutation analysis performed in 36 families led to the
      identification of 12 novel mutations, eight of which were small
      deletions/insertions. Large deletions/rearrangements and all but one small
      deletion/insertion led to a severe phenotype. This genotype-phenotype correlation
      was also identified in six cases with recurrent missense mutations. Based on
      patient genotype, the severity of the disease may be predicted with high
      probability in approximately half of MPS II patients.

PMID- 27883180
TI  - Mitochondrial reactive oxygen species suppress humoral immune response through
      reduction of CD19 expression in B cells in mice.
AB  - Reactive oxygen species (ROS) are implicated in the modulation of diverse
      processes including immune responses. To evaluate the effects of metabolic ROS
      produced by mitochondria on B-cell function and development, we created
      transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate
      dehydrogenase A in B cells (bSDHAY215F ). Splenic B cells in male, but not
      female, bSDHAY215F mice produced three times more ROS than those in the control
      mice, and had decreased production of IgM, IgG1 , and IgG3 , and affinity
      maturation of IgG1 against T-cell-dependent antigens. Following immunization, the
      male bSDHAY215F mice further displayed suppressed germinal center (GC) formation,
      and proliferation of GC B cells. Signaling analysis revealed defects in the
      intrinsic BCR responses, such as activation of Lyn, Btk, and PLCgamma2, thus
      resulting in reduced intracellular Ca2+ mobilization. Notably, the expression
      levels of B-cell co-receptor CD19 and its interaction with Lyn after BCR ligation
      were significantly reduced in B cells from male bSDHAY215F mice. These results
      suggest that mitochondrial ROS suppress humoral immune responses through
      reduction of CD19 expression and resultant BCR signaling in B cells. Therefore, B
      cell immunity may be more labile to oxidative stress in male mice than in female
      mice.

PMID- 27883179
TI  - Evidence that an internal schema adapts swallowing to upper airway requirements.
AB  - KEY POINTS: To swallow food and liquid safely, airway protection is essential.
      Upward and forward movements of the hyoid and larynx in the neck during
      swallowing vary in magnitude between individuals. In healthy human adults, hyoid
      and laryngeal movements during swallowing were scaled by differences in initial
      upper airway area before swallowing. Individuals increased laryngeal elevation
      during swallowing in response to increased airway opening before swallowing. We
      show that when upper airway protection requirements change, individuals use an
      internal sensorimotor scaling system to adapt movements to maintain swallow
      safety. ABSTRACT: Hyoid and laryngeal movements contribute to laryngeal vestibule
      closure and upper oesophageal sphincter opening during swallowing. Evidence of an
      internal sensorimotor scaling system allowing individuals to achieve these
      functional goals is lacking. In speech, speakers adjust their articulatory
      movement magnitude according to the movement distance required to reach an
      articulatory target for intelligible speech. We investigated if swallowing is
      similar in that movement amplitude may be scaled by the functional goal for
      airway protection during swallowing, rather than by head and neck size. We
      hypothesized that healthy individuals adapt to their own anatomy by adjusting hyo
      laryngeal movements to achieve closure of the upper airway. We also investigated
      if individuals would automatically compensate for changes in their initial hyo
      laryngeal positions and area when head position was changed prior to swallowing.
      Videofluoroscopy was performed in 31 healthy adults. Using frame-by-frame motion
      analysis, anterior and superior hyoid and laryngeal displacement, and hyo
      laryngeal area were measured prior to and during swallowing. Kinematic
      measurements during swallowing were examined for relationships with pharyngeal
      neck length, and initial hyo-laryngeal positions, length and area before
      swallowing. During swallowing, individuals altered laryngeal elevation magnitude
      to exceed hyoid elevation based on hyo-laryngeal length before swallowing.
      Anterior laryngeal displacement was related to initial larynx distance from the
      spine, while hyoid elevation was predicted by pharyngeal neck length and initial
      hyoid distance from the mandible prior to the swallow. In conclusion, individuals
      automatically adapt hyo-laryngeal movement during swallowing based on targets
      required for closing the hyo-laryngeal area for safe swallowing.

PMID- 27883182
TI  - The benefit of thresholding carbon layers in electron tomographic tilt series by
      intensity downshifting.
AB  - When performing electron tomography, tilt series of images are often acquired
      from samples that contain unwanted carbonaceous material, such as an embedding
      resin, a thin carbon support film or hydrocarbon contamination. The presence of
      such layers can introduce artefacts in reconstructions, obscuring features of
      interest. Here, we illustrate the benefit of preprocessing a high-angle annular
      dark-field tomographic tilt series by thresholding unwanted low-density materials
      using a simple intensity downshifting procedure. The resulting tomograms have
      fewer artefacts and segmentation can be performed more accurately. We present two
      representative examples taken from studies of catalyst nanoparticles and amyloid
      plaque core material from the human brain.

PMID- 27883181
TI  - WONOEP appraisal: Imaging biomarkers in epilepsy.
AB  - Neuroimaging offers a wide range of opportunities to obtain information about
      neuronal activity, brain inflammation, blood-brain barrier alterations, and
      various molecular alterations during epileptogenesis or for the prediction of
      pharmacoresponsiveness as well as postoperative outcome. Imaging biomarkers were
      examined during the XIII Workshop on Neurobiology of Epilepsy (XIII WONOEP)
      organized in 2015 by the Neurobiology Commission of the International League
      Against Epilepsy (ILAE). Here we present an extended summary of the discussed
      issues and provide an overview of the current state of knowledge regarding the
      biomarker potential of different neuroimaging approaches for epilepsy.

PMID- 27883183
TI  - Effect of nanoclay concentration level on the electrical properties of
      polypropylene under electron irradiation in a SEM.
AB  - For studying the electrical properties (charge trapping, transport and secondary
      electron emission) of the polypropylene-based nanocomposites with different
      contents of natural clay, the specimens were submitted to electron irradiation of
      a scanning electron microscope. A device, suitably mounted on the sample holder
      of the scanning electron microscope, was used to measure two currents (i.e.
      leakage and displacement currents) induced in the polypropylene-based
      nanocomposites (polymer nanocomposites) under electron irradiation. The evolution
      of trapped charge during irradiation for each type of studied polymer
      nanocomposites is deduced. The amount of trapped charge at the steady state is
      also determined by measuring the change of secondary electron image size
      associated to the electron trajectory simulation. It is found, surprisingly, that
      not only the leakage current increases as a function of clay loading level but
      also trapped charge. However, this could be related to the increase of
      conductivity in one hand and to proliferation of interfaces between nanoparticles
      and neighbouring materials on the other hand. These two processes play crucial
      role in controlling the carrier transport (through polymer nanocomposites or/and
      along its surface) closely related to the charge storage and leakage current.
      Additional experiment using dielectric spectroscopy were performed to show the
      effect of clay concentration in changing the dielectric relaxation behaviour and
      to evidence the existence of interfaces between nanoparticles and polymer. The
      secondary electron emission during electron irradiation is also studied through
      the total electron yield that is deduced by correlating the measured leakage and
      displacement currents.

PMID- 27883184
TI  - Epigenetics in Reactive and Reparative Cardiac Fibrogenesis: The Promise of
      Epigenetic Therapy.
AB  - Epigenetic changes play a pivotal role in the development of a wide spectrum of
      human diseases including cardiovascular diseases, cancer, diabetes, and
      intellectual disabilities. Cardiac fibrogenesis is a common pathophysiological
      process seen during chronic and stress-induced accelerated cardiac aging. While
      adequate production of extracellular matrix (ECM) proteins is necessary for post
      injury wound healing, excessive synthesis and accumulation of extracellular
      matrix protein in the stressed or injured hearts causes decreased or loss of
      lusitropy that leads to cardiac failure. This self-perpetuating deposition of
      collagen and other matrix proteins eventually alter cellular homeostasis; impair
      tissue elasticity and leads to multi-organ failure, as seen during pathogenesis
      of cardiovascular diseases, chronic kidney diseases, cirrhosis, idiopathic
      pulmonary fibrosis, and scleroderma. In the last 25 years, multiple studies have
      investigated the molecular basis of organ fibrosis and highlighted its multi
      factorial genetic, epigenetic, and environmental regulation. In this minireview,
      we focus on five major epigenetic regulators and discuss their central role in
      cardiac fibrogenesis. Additionally, we compare and contrast the epigenetic
      regulation of hypertension-induced reactive fibrogenesis and myocardial
      infarction-induced reparative or replacement cardiac fibrogenesis. As microRNAs
      one of the major epigenetic regulators-circulate in plasma, we also advocate
      their potential diagnostic role in cardiac fibrosis. Lastly, we discuss the
      evolution of novel epigenetic-regulating drugs and predict their clinical role in
      the suppression of pathological cardiac remodeling, cardiac aging, and heart
      failure. J. Cell. Physiol. 232: 1941-1956, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883185
TI  - Water dynamics of Ser-His-Glu-Cys-Asn powder and effects of moisture absorption
      on its chemical properties.
AB  - BACKGROUND: This study has elucidated moisture dynamics in the soybean peptide,
      Ser-His-Glu-Cys-Asn (SHECN) powder by using dynamic vapor sorption (DVS) and
      nuclear magnetic resonance (NMR). We also tried to investigate the effects of
      moisture absorption on the biological activity and chemical properties of SHECN
      with some effective methods such as mid-infrared (MIR) spectroscopy and gas
      chromatography-mass spectrometry (GC-MS). RESULTS: DVS results showed that the
      moisture absorption of SHECN could reach a maximum of 33%, and the SHECN powder
      after synthesis actually existed in a trihydrate state of SHECN.3H2 O. Low-field
      NMR revealed that three water proportions including strong combined water,
      binding water and bulk water were involved in SHECN moisture absorption and
      absored water dominantly existed in the form of combined water. Magnetic
      resonance imaging (MRI) and MIR spectroscopy results indicated that moisture
      absorption could change the morphology and structure of SHECN. After moisture
      absorption at 50% and 75% relative humidity, 19 volatiles were identified by GC
      MS analysis. Additionally, this study showed that a part of reductive groups in
      SHECN was oxidized and its antioxidant ability declined significantly (P < 0.05)
      after moisture absorption. CONCLUSION: Water absorbed into SHECN powder can
      significantly change its microstructure and cause its activity to decrease. We
      must prevent SHECN from absorbing moisture during storage because the water can
      accelerate the oxidation of samples and promote microbial reactions. (c) 2016
      Society of Chemical Industry.

PMID- 27883186
TI  - Lactate at the crossroads of metabolism, inflammation, and autoimmunity.
AB  - For a long time after its discovery at the beginning of the 20th century, lactate
      was considered a waste product of cellular metabolism. Starting in the early
      '90s, however, lactate has begun to be recognized as an active molecule capable
      of modulating the immune response. Inflammatory sites, including in rheumatoid
      arthritis (RA) synovitis, are characterized by the accumulation of lactate, which
      is partly responsible for the establishment of an acidic environment. We have
      recently reported that T cells sense lactate via the expression of specific
      transporters, leading to inhibition of their motility. Importantly, this "stop
      migration signal" is dependent upon lactate's interference with intracellular
      metabolic pathways, specifically glycolysis. Furthermore, lactate promotes the
      switch of CD4+ T cells to an IL-17+ subset, and reduces the cytolytic capacity of
      CD8+ T cells. These phenomena might be responsible for the formation of ectopic
      lymphoid structures and autoantibody production in inflammatory sites such as in
      RA synovitis, Sjogren syndrome salivary glands, and multiple sclerosis plaques.
      Here, we review the roles of lactate in the modulation of the inflammatory immune
      response.

PMID- 27883187
TI  - Molybdenum and phosphorus limitation of moss-associated nitrogen fixation in
      boreal ecosystems.
AB  - Biological nitrogen fixation (BNF) performed by moss-associated cyanobacteria is
      one of the main sources of new nitrogen (N) input in pristine, high-latitude
      ecosystems. Yet, the nutrients that limit BNF remain elusive. Here, we tested
      whether this important ecosystem function is limited by the availability of
      molybdenum (Mo), phosphorus (P), or both. BNF in dominant mosses was measured
      with the acetylene reduction assay (ARA) at different time intervals following Mo
      and P additions, in both laboratory microcosms with mosses from a boreal spruce
      forest and field plots in subarctic tundra. We further used a 15 N2 tracer
      technique to assess the ARA to N2 fixation conversion ratios at our subarctic
      site. BNF was up to four-fold higher shortly after the addition of Mo, in both
      the laboratory and field experiments. A similar positive response to Mo was found
      in moss colonizing cyanobacterial biomass. As the growing season progressed,
      nitrogenase activity became progressively more P limited. The ARA : 15 N2 ratios
      increased with increasing Mo additions. These findings show that N2 fixation
      activity as well as cyanobacterial biomass in dominant feather mosses from boreal
      forests and subarctic tundra are limited by Mo availability.

PMID- 27883188
TI  - Structural organization and tooth development in a Homo aff. erectus juvenile
      mandible from the Early Pleistocene site of Garba IV at Melka Kunture, Ethiopian
      highlands.
AB  - OBJECTIVES: The immature partial mandible GAR IVE from the c. 1.7 Ma old Garba IV
      site at Melka Kunture (Upper Awash Basin, Ethiopia), the earliest human
      representative from a mountain-like environment, represents one of the oldest
      early Homo specimens bearing a mixed dentition. Following its first description
      (Condemi, ), we extended the analytical and comparative record of this specimen
      by providing unreported details about its inner morphology, tooth maturational
      pattern and age at death, crown size, and tooth tissue proportions. MATERIALS AND
      METHODS: The new body of quantitative structural information and virtual imaging
      derives from a medical CT record performed in 2013. RESULTS: Compared to the
      extant human condition and to some fossil representatives of comparable
      individual age, the GAR IVE mandible reveals absolutely and relatively thick
      cortical bone. Crown size of the permanent lateral incisor and the canine fit the
      estimates of H. erectus s.l., while the dm2 and the M1 more closely approach
      those of H. habilis-rudolfensis. Molar crown pulp volumes are lower than reported
      in other fossil specimens and in extant humans. The mineralization sequence of
      the permanent tooth elements is represented four times in our reference sample of
      extant immature individuals (N = 795). CONCLUSIONS: The tooth developmental
      pattern displayed by the immature individual from Garba IV falls within the range
      of variation of extant human populations and is also comparable with that of
      other very young early fossil hominins. Taken together, the evidence presented
      here for mandibular morphology and dental development suggest GAR IVE is a robust
      2.5- to 3.5-year old early Homo specimen.

PMID- 27883189
TI  - Family Correlates of False Belief Understanding in Early Childhood: A Meta
      Analysis.
AB  - This meta-analysis seeks to integrate findings from 25 years of research on
      family correlates of young children's false belief understanding (FBU). Using
      data from 93 studies of 3- to 7-year-old children, we examined the correlations
      between FBU and four of the most widely studied family factors: parental
      socioeconomic status, number of siblings, parental mental-state talk, and mind
      mindedness. FBU exhibited modest associations with each family variable and these
      associations held even when individual differences in verbal ability were taken
      into account. Moderator analyses revealed key child-related factors (e.g., age,
      gender) as well as methodological factors that amplified or attenuated the
      relations between FBU and each family variable. Crucially, available longitudinal
      data highlight the importance of family factors in the development of FBU.

PMID- 27883191
TI  - Shyness and Social Conflict Reduce Young Children's Social Helpfulness.
AB  - This study examined social influences on 3-year-old children's decisions to help
      an experimenter gain another person's attention (N = 32). Children were slower to
      help the experimenter when the target had previously expressed disinterest in
      attending to her. Shy children were less likely to support the experimenter's
      attempts to communicate with the target; however, this association was not
      influenced by children's knowledge of the target's disinterest, and there was no
      relation between shyness and children's support for a separate physical goal.
      Therefore, young children's decisions to act helpfully incorporate consideration
      for others beyond a focal person with an unmet need, and they are further
      constrained by children's own comfort with the actions required to help.

PMID- 27883190
TI  - Environmental control of carbon allocation matters for modelling forest growth.
AB  - We aimed to evaluate the importance of modulations of within-tree carbon (C)
      allocation by water and low-temperature stress for the prediction of annual
      forest growth with a process-based model. A new C allocation scheme was
      implemented in the CASTANEA model that accounts for lagged and direct
      environmental controls of C allocation. Different approaches (static vs dynamic)
      to modelling C allocation were then compared in a model-data fusion procedure,
      using satellite-derived leaf production estimates and biometric measurements at
      c. 104 sites. The modelling of the environmental control of C allocation
      significantly improved the ability of CASTANEA to predict the spatial and year-to
      year variability of aboveground forest growth along regional gradients. A
      significant effect of the previous year's water stress on the C allocation to
      leaves and wood was reported. Our results also are consistent with a prominent
      role of the environmental modulation of sink demand in the wood growth of the
      studied species. Data available at large scales can inform forest models about
      the processes driving annual and seasonal C allocation. Our results call for a
      greater consideration of C allocation drivers, especially sink-demand
      fluctuations, for the simulations of current and future forest productivity with
      process-based models.

PMID- 27883192
TI  - A call to action to reshape evidence synthesis and use for nutrition policy.

PMID- 27883193
TI  - Auxin transport in the evolution of branching forms.
AB  - Contents 545 I. 545 II. 546 III. 546 IV. 548 V. 548 VI. 549 VII. 549
      Acknowledgements 549 References 549 SUMMARY: Branching is one of the most
      striking aspects of land plant architecture, affecting resource acquisition and
      yield. Polar auxin transport by PIN proteins is a primary determinant of
      flowering plant branching patterns regulating both branch initiation and branch
      outgrowth. Several lines of experimental evidence suggest that PIN-mediated polar
      auxin transport is a conserved regulator of branching in vascular plant
      sporophytes. However, the mechanisms of branching and auxin transport and
      relationships between the two are not well known outside the flowering plants,
      and the paradigm for PIN-regulated branching in flowering plants does not fit
      bryophyte gametophytes. The evidence reviewed here suggests that divergent auxin
      transport routes contributed to the diversification of branching forms in
      distinct land plant lineages.

PMID- 27883194
TI  - Matworld - the biogeochemical effects of early life on land.
AB  - Contents 531 I. 531 II. 532 III. 534 IV. 535 V. 535 VI. 535 Acknowledgements 536
      References 536 SUMMARY: There is growing evidence that life has been on land for
      billions of years. Microbial mats fuelled by oxygenic photosynthesis were
      probably present in terrestrial habitats from c. 3.0 billion yr ago (Ga) onwards,
      creating localized 'oxygen oases' under a reducing atmosphere, which left a
      characteristic oxidative weathering signal. After the Great Oxidation c. 2.4 Ga,
      the now oxidizing atmosphere masked that redox signal, but ancient soils record
      the mobilization of phosphorus and other elements by organic acids in weathering
      profiles. Evidence for Neoproterozoic 'greening of the land' and intensification
      of weathering c. 0.85-0.54 Ga is currently equivocal. However, the mid-Palaeozoic
      c. 0.45-0.4 Ga shows global atmospheric changes consistent with increased
      terrestrial productivity and intensified weathering by the first land plants.

PMID- 27883196
TI  - Grifolin derivatives from Albatrellus ovinus as TRPV1 receptor blockers for
      cosmetic applications.
AB  - OBJECTIVE: Blocking the TRPV1 receptor is an interesting approach for the
      treatment of sensitive skin. Here we investigated the potential of grifolin
      derivatives from Albatrellus ovinus to act as TRPV1 receptor blockers and their
      potential to serve as cosmetic active ingredients. METHODS: Binding
      characteristics of grifolin derivatives from Albatrellus ovinus were determined
      in competitive and functional in vitro assays to achieve IC50 values. The TRPV1
      receptor was activated in vivo with capsaicin and noxious heat to investigate
      skin reddening, microcirculation, skin sensations and heat pain thresholds.
      RESULTS: Grifolin derivatives extracted from Albatrellus ovinus proved to inhibit
      the TRPV1 receptor in vitro and in vivo. Besides suppression of the TRPV1
      receptor activity upon chemical stimulation with capsaicin, thermal activation
      was shown to be inhibited as well by application of cosmetic formulations
      containing 3% Albatrellus ovinus extract. The reduction of stinging and burning
      sensations as well as reduction of reddening and microcirculation upon irritation
      with capsaicin or thermal stress proved efficacy in vivo. CONCLUSION: Grifolin
      derivatives from Albatrellus ovinus are able to serve as fungal-derived TRPV1
      receptor blockers with capability to serve as a cosmetic active ingredient on
      sensitive skin.

PMID- 27883195
TI  - The Use of Cardiac Orienting Responses as an Early and Scalable Biomarker of
      Alcohol-Related Neurodevelopmental Impairment.
AB  - BACKGROUND: Considered the leading cause of developmental disabilities worldwide,
      fetal alcohol spectrum disorders (FASD) are a global health problem. To take
      advantage of neural plasticity, early identification of affected infants is
      critical. The cardiac orienting response (COR) has been shown to be sensitive to
      the effects of prenatal alcohol exposure and is an inexpensive, easy to
      administer assessment tool. The purpose of this study was to evaluate the COR
      effectiveness in assessing individual risk of developmental delay. METHODS: As
      part of an ongoing longitudinal cohort study in Ukraine, live-born infants of
      women with some to heavy amounts of alcohol consumption in pregnancy were
      recruited and compared to infants of women who consumed low or no alcohol. At 6
      and 12 months, infants were evaluated with the Bayley Scales of Infant
      Development-II. CORs were also collected during a habituation/dishabituation
      learning paradigm. Using a supervised logistic regression classifier, we compared
      the predictive utility of the COR indices to that of the 6-month Bayley scores
      for identification of developmental delay based on 12-month Bayley scores. Heart
      rate collected at each second (Standard COR) was compared to key features (Key
      COR) extracted from the response. RESULTS: Negative predictive values (NPV) were
      85% for Standard COR, 82% for Key COR, and 77% for the Bayley, and positive
      predictive values (PPV) were 66% for Standard COR, 62% for Key COR, and 43% for
      the Bayley. CONCLUSIONS: Predictive analysis based on the COR resulted in better
      NPV and PPV than the 6-month Bayley score. As the resources required to obtain a
      Bayley score are substantially more than in a COR-based paradigm, the findings
      are suggestive of its utility as an early scalable screening tool based on the
      COR. Further work is needed to test its long-term predictive accuracy.

PMID- 27883197
TI  - Cultivating Community Psychology for Future Generations: Symbiosis, Synergy, and
      Separation.
AB  - As we near the fiftieth anniversary of the founding of a community psychology
      division of the American Psychological Association, there are reasons to be
      concerned about the sustainability of the field. This commentary proposes a need
      for deliberate, systematic efforts to cultivate settings that can sustain the
      field. A framework for outreach to build symbiotic relationships and synergistic
      collaborations with persons who do not identify as community psychologists is
      proposed. Simultaneously, a strategy of separation from other disciplines may be
      needed in some circumstances to conserve settings that sustain the field. Finding
      a balance in these strategies is necessary to cultivate community psychology for
      future generations.

PMID- 27883198
TI  - Reflections on a Community Psychology Setting and the Future of the Field.
AB  - The 50th anniversary of the Swampscott Conference offers an opportunity to
      reflect on a community psychology setting, The Consultation Center at Yale, that
      was formed in response to the 1963 Community Mental Health Act and the 1965
      Swampscott Conference. The Center has flourished as a community psychology
      setting for practice, research, and training for 39 of the 50 years since
      Swampscott. Its creation and existence over this period offers an opportunity for
      reflection on the types of settings needed to sustain the field into the future.

PMID- 27883199
TI  - Hepcidin detects iron deficiency in Sri Lankan adolescents with a high burden of
      hemoglobinopathy: A diagnostic test accuracy study.
AB  - Anemia affects over 800 million women and children globally. Measurement of
      hepcidin as an index of iron status shows promise, but its diagnostic performance
      where hemoglobinopathies are prevalent is unclear. We evaluated the performance
      of hepcidin as a diagnostic test of iron deficiency in adolescents across Sri
      Lanka. We selected 2273 samples from a nationally representative cross-sectional
      study of 7526 secondary schoolchildren across Sri Lanka and analyzed associations
      between hepcidin and participant characteristics, iron indices, inflammatory
      markers, and hemoglobinopathy states. We evaluated the diagnostic accuracy of
      hepcidin as a test for iron deficiency with estimation of the AUCROC ,
      sensitivity/specificity at each hepcidin cutoff, and calculation of the Youden
      Index to find the optimal threshold. Hepcidin was associated with ferritin, sTfR,
      and hemoglobin. The AUCROC for hepcidin as a test of iron deficiency was 0.78;
      hepcidin outperformed Hb and sTfR. The Youden index-predicted cutoff to detect
      iron deficiency (3.2 ng/mL) was similar to thresholds previously identified to
      predict iron utilization and identify deficiency in African populations. Neither
      age, sex, nor alpha- or beta-thalassemia trait affected diagnostic properties of
      hepcidin. Hepcidin pre-screening would prevent most iron-replete thalassemia
      carriers from receiving iron whilst still ensuring most iron deficient children
      were supplemented. Our data indicate that the physiological relationship between
      hepcidin and iron status transcends specific populations. Measurement of hepcidin
      in individuals or populations could establish the need for iron interventions.
      Am. J. Hematol. 92:196-203, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883201
TI  - Effect of treatment with 5-lipoxygenase inhibitor VIA-2291 (atreleuton) on
      coronary plaque progression: a serial CT angiography study.
AB  - BACKGROUND: Inflammation has a key role in the process of atherosclerosis.
      Production of leukotrienes by 5-lipoxygenase has been linked to atherosclerotic
      plaques and cardiovascular events. HYPOTHESIS: In this study, a selective 5-LO
      inhibitor will slow plaque progression using serial cardiac computed tomographic
      angiography (CCTA). METHODS: Patients with recent acute coronary syndrome (ACS)
      were prospectively assigned to one of 3 VIA-2291 doses (25 mg, 50 mg, 100 mg) or
      placebo by oral administration. All groups underwent CCTA at baseline and at 6
      months' follow-up. Plaque types such as low-attenuation plaque (LAP), fibro-fatty
      tissue (FF), fibro-calcified plaque (FC), and dense calcium plaque (DC) were
      measured based upon predefined density threshold, and changes from baseline CCTA
      were analyzed. RESULTS: The final analysis included 54 patients (age, 56 +/- 9
      years; 85.1% male) with CCTA at baseline and 24 weeks. Evaluating on treatment
      VIA-2291 (all 3 doses, n = 37) demonstrated significant reductions in plaque
      progression compared with placebo (n = 17). VIA-2291 significantly reduced LAP
      (5.9 +/- 20.7 mm3 vs -9.7 +/- 33.3 mm3 ), FF (11.1 mm3  +/- 13.3 mm3 vs -0.9 +/-
      2.7 mm3 ), and FC (-0.1 +/- 6.22 mm3 vs -14.3 +/- 6.2 mm3 ; all P < 0.05) and
      retarded the progression of DC (3.9 +/- 3.2 mm3 vs 0.2 +/- 0.4 mm3 ) compared
      with placebo. CONCLUSIONS: VIA-2291 resulted in slowed plaque progression
      compared with placebo across different plaque subtypes in patients with recent
      ACS (http://ClinicalTrials.gov NCT00358826).

PMID- 27883200
TI  - A new way to estimate disease prevalence from random partial-mouth samples.
AB  - AIM: Standard partial-mouth estimators of chronic periodontitis (CP) that define
      an individual's disease status solely in terms of selected sites underestimate
      prevalence. This study proposes an improved prevalence estimator based on
      randomly sampled sites and evaluates its accuracy in a well-characterized
      population cohort. METHODS: Importantly, this method does not require
      determination of disease status at the individual level. Instead, it uses a
      statistical distributional approach to derive a prevalence formula from randomly
      selected periodontal sites. The approach applies the conditional linear family of
      distributions for correlated binary data (i.e. the presence or absence of disease
      at sites within a mouth) with two simple working assumptions: (i) the probability
      of having disease is the same across all sites; and (ii) the correlation of
      disease status is the same for all pairs of sites within the mouth. RESULTS:
      Using oral examination data from 6793 participants in the Arteriolosclerosis Risk
      in Communities study, the new formula yields CP prevalence estimates that are
      much closer than standard partial mouth estimates to full mouth estimates.
      CONCLUSIONS: Resampling of the cohort shows that the proposed estimators give
      good precision and accuracy for as few as six tooth sites sampled per individual.

PMID- 27883202
TI  - The role of platelets in inflammatory immune responses in generalized aggressive
      periodontitis.
AB  - AIM: To investigate the relationship between inflammatory markers and platelet
      size in generalized aggressive periodontitis (GAgP). MATERIAL AND METHODS:
      Periodontal, inflammatory and platelet indices were compared between 59 GAgP
      patients and 59 healthy subjects. Gingival biopsies from five patients and five
      healthy subjects were examined by immunohistochemistry and electron microscopy.
      Changes in patient periodontal and platelet indices were re-evaluated at 3 months
      after periodontal therapy. RESULTS: Platelet size was decreased significantly in
      GAgP patients compared to healthy subjects (p <= 0.003). Weak negative
      correlations between platelet size and periodontal parameters were found in GAgP
      patients (p <= 0.025). Platelet aggregates and adhesion to the endothelium or
      leucocytes were found in venules and connective tissues of gingival biopsies from
      GAgP patients. Mean platelet volume (MPV) and platelet large cell ratio increased
      after periodontal therapy in GAgP patients (p <= 0.038). The increase in MPV was
      related to the decrease in bleeding index in GAgP patients after periodontal
      therapy (p < 0.001; r = 0.357). CONCLUSION: Platelet size was reduced in GAgP
      patients compared to healthy controls, possibly due to the consumption of large
      platelets at sites of periodontal inflammation. Platelets may be involved in host
      responses to periodontal infection in GAgP.

PMID- 27883203
TI  - Impact of platform switching on inter-proximal bone levels around 8.5 mm implants
      in the posterior region; 5-year results from a randomized clinical trial.
AB  - AIM: To assess the medium-term results of 8.5 mm implants supplied with a
      conventional platform-matched implant-abutment connection or a platform-switched
      design. MATERIALS AND METHODS: Eighty patients with one or more missing teeth in
      the maxillary or mandibular posterior zone were randomly assigned for treatment
      with implants with a conventional (control group) or platform-switched (test
      group) implant-abutment connection. Follow-up visits were conducted 1 month, 1
      year and 5 years after functional loading. Inter-proximal bone loss, assessed
      with standardized peri-apical radiographs, clinical parameters, survival of
      implants and satisfaction of patients were the outcome parameters studied.
      RESULTS: After 5 years of loading, five of the 80 patients were lost to follow
      up. The inter-proximal bone loss in the test group (0.38 +/- 0.61 mm) was
      comparable to the bone loss in the control group (0.41 +/- 0.47 mm; p = 0.201).
      Remarkably, bone loss has not progressed compared to the 1-year results. Implant
      survival, clinical parameters and satisfaction of the patients were favourable
      and comparable for the test and control group. CONCLUSION: The 5-years results
      showed that inter-proximal bone resorption was minor and comparable around
      platform-matched and platform-switched implants, and implant survival, peri
      implant health and patients' satisfaction were favourable.

PMID- 27883204
TI  - Mindfulness Moderates the Association Between Perceived Burdensomeness and
      Suicide Ideation in Adults With Elevated Depressive Symptoms.
AB  - A conceptual model in which the associations between perceived burdensomeness and
      suicide ideation, and between thwarted belongingness and suicide ideation, are
      moderated by mindfulness was examined. Participants were 218 undergraduates (mean
      age = 20.81) with moderate-to-severe depressive symptoms. Mindfulness
      significantly moderated the association between perceived burdensomeness and
      suicide ideation; participants with thoughts of burdensomeness experienced lower
      levels of suicide ideation if they were high, as opposed to low, in mindfulness.
      Mindfulness did not significantly moderate the association between thwarted
      belongingness and suicide ideation. Implications for intervention and elaboration
      of the interpersonal psychological theory of suicide are discussed.

PMID- 27883205
TI  - Root and root canal morphology of the permanent dentition in a Caucasian
      population: a cone-beam computed tomography study.
AB  - AIM: To investigate in vivo the number of roots, the configuration of the root
      canal system and the root canal splitting and merging levels in the permanent
      dentition of a Caucasian population. METHODOLOGY: A total of 11 892 teeth were
      inspected in cone-beam computed tomography examinations that were collected from
      a pre-existing database. The number of roots was identified, and canal
      configurations were classified according to Vertucci's classification and its
      supplemental configurations. In addition, the merging and separation positions
      along the length of the root canal were identified. The Z-test was used to
      analyse the differences between independent groups. A value of P < 0.05 was
      considered significant. RESULTS: The majority of tooth types had considerable
      variation in the number of roots and root canal configuration types. Radix
      entomolaris and paramolaris were rare occurrences. The mesiobuccal root of the
      maxillary first and second molars had two root canals in 71% and 44% of cases,
      respectively. Nearly 30% of the mandibular incisors had two root canals. Root
      canal merging and splitting appeared more often in mandibular teeth. Merging was
      more common in the middle third of the root canal in the maxillary teeth and in
      the middle and apical thirds in mandibular teeth. Root canal splitting did not
      exhibit a tendency, and their position along the length of the root canal varied
      from tooth to tooth. CONCLUSION: Clinicians must be aware that each tooth may
      display several types of root canal configuration. However, a greater variability
      in root canal configuration was found in maxillary second premolars and in the
      mesiobuccal roots of maxillary molars. Main root canal merging and splitting may
      also be expected to occur at any level of the root canal.

PMID- 27883206
TI  - Diffuse pulmonary extramedullary hematopoiesis in myelofibrosis diagnosed with
      technetium-99m sulfur colloid bone marrow scintigraphy and single photon emission
      computerized tomography/CT.

PMID- 27883207
TI  - Interpersonal-Psychological Theory, Alexithymia, and Personality Predict Suicide
      Ideation among Maladjusted Soldiers in Taiwan.
AB  - This case-control study enrolled 226 maladjusted soldiers and 229 controls to
      investigate the impact of the interpersonal-psychological theory of suicide,
      alexithymia, personality, and childhood trauma on suicide risk among Taiwanese
      soldiers. Assessments included the Toronto Alexithymia Scale, Eysenck Personality
      Inventory, Mini-International Neuropsychiatric Interview, and Brief Symptom
      Rating Scale. In addition to thwarted belongingness and perceived burdensomeness,
      other risks included less extraversion with higher neuroticism, higher
      alexithymia, poor academic performance, domestic violence, and life-threatening
      events. Our study demonstrates the interaction of the interpersonal-psychological
      theory and other suicide risk factors in Taiwanese soldiers.

PMID- 27883208
TI  - The association between dentition status and sarcopenia in Japanese adults aged
      >=75 years.
AB  - Sarcopenia is an age-related loss of muscle mass and muscle strength or physical
      performance. There are limited data on the association between oral health and
      sarcopenia. To test the hypothesis that impaired dentition status was associated
      with sarcopenia, we conducted a cross-sectional study. A total of 272 community
      dwelling Japanese adults aged >=75 years for whom data were available from
      comprehensive health examinations conducted in 2015 were included in this study.
      During dental examination, the number of natural teeth and occluding pairs of
      natural teeth was counted. In denture wearers, the fit of the removable dentures
      was also evaluated. The criteria proposed by the Asian Working Group for
      Sarcopenia were used to define sarcopenia. A multivariable logistic regression
      model was used to evaluate the association between dentition status and the
      presence of sarcopenia. The prevalence of sarcopenia was 25.7% (70/272). Compared
      to individuals with >=10 occluding pairs of natural teeth, those with no
      occluding pairs of natural teeth had significantly higher risk of having
      sarcopenia (adjusted odds ratio, 3.37; 95% confidence interval, 1.07-10.61),
      after adjusting for possible confounders. In addition, compared to individuals
      with well-fitting dentures, those with ill-fitting dentures had significantly
      higher risk of having sarcopenia (adjusted odds ratio, 5.07; 95% confidence
      interval, 1.59-16.19). Our findings suggest that impaired dentition status is
      significantly associated with sarcopenia among community-dwelling Japanese adults
      aged >=75 years. Future longitudinal studies with larger, more diverse
      populations are necessary to validate our findings.

PMID- 27883209
TI  - Tongue-to-palate resistance training improves tongue strength and oropharyngeal
      swallowing function in subacute stroke survivors with dysphagia.
AB  - Tongue function can affect both the oral and pharyngeal stages of the swallowing
      process, and proper tongue strength is vital for safe oropharyngeal swallowing.
      This trial investigated the effect of tongue-to-palate resistance training (TPRT)
      on tongue strength and oropharyngeal swallowing function in stroke with dysphagia
      patients. This trial was performed using a 4-week, two-group, pre-post-design.
      Participants were allocated to the experimental group (n = 18) or the control
      group (n = 17). The experimental group performed TPRT for 4 weeks (5 days per
      week) and traditional dysphagia therapy, whereas the control group performed
      traditional dysphagia therapy on the same schedule. Tongue strength was measured
      using the Iowa Oral Performance Instrument. Swallowing function was measured
      using the videofluoroscopic dysphagia scale (VDS) and penetration-aspiration
      scale (PAS) based on a videofluoroscopic swallowing study. Experimental group
      showed more improved in the tongue strength (both anterior and posterior regions,
      P = 0.009, 0.015). In addition, the experimental group showed more improved
      scores on the oral and pharyngeal phase of VDS (P = 0.029, 0.007), but not on the
      PAS (P = 0.471), compared with the control group. This study demonstrated the
      effectiveness of TPRT in increasing tongue muscle strength and improving
      swallowing function in patients with post-stroke dysphagia. Therefore, we
      recommend TPRT as an easy and simple rehabilitation strategy for improving
      swallowing in patients with dysphagia.

PMID- 27883210
TI  - Rationale and design of the BAYES (Interatrial Block and Yearly Events) registry.
AB  - The prevalence of interatrial block (IAB) is high in the elderly, particularly in
      those with heart disease. Despite this high prevalence-and the association of IAB
      with the risk of atrial fibrillation (AF), stroke, and cognitive decline-little
      information exists about the prognosis of older patients with IAB. P-wave
      duration and morphology are associated with risk of developing AF, stroke, and
      cognitive decline in elderly patients with structural heart disease. The aim of
      the Interatrial Block and Yearly Events (BAYES) registry is to assess the impact
      of IAB on the risk of AF and stroke during 3 years of follow-up. A series of 654
      ambulatory patients age >=70 years with heart disease from 35 centers will be
      included in 3 similar-size groups of patients. Group A: normal P-wave duration
      (<120 ms); Group B: partial IAB (P-wave duration >=120 ms without biphasic
      [plus/minus] morphology in the inferior leads II, III, and aVF); and Group C:
      advanced IAB (P-wave duration >=120 ms with biphasic [plus/minus] morphology in
      the inferior leads II, III, and aVF). Patients will be managed according to
      current recommendations. The 2 primary endpoints are defined as (1) AF duration
      >5 minutes and documented in any form of electrocardiographic recording; and (2)
      stroke. Results from this study might significantly improve the knowledge of IAB
      and its impact on the outcome of elderly patients with heart disease and could
      open the door to the use of anticoagulation therapy in some elderly patients with
      IAB.

PMID- 27883211
TI  - Clinical and Histological changes after ridge preservation with two xenografts:
      preliminary results from a multicentre randomized controlled clinical trial.
AB  - OBJECTIVES: To evaluate and compare clinical and histological changes after ridge
      preservation procedures with those of spontaneous healing. MATERIALS AND METHODS:
      Ninety patients were enrolled in the present randomized controlled clinical trial
      and underwent single-tooth extraction in the premolar/molar areas. Thirty sites
      were grafted with collagenated cortico-cancellous (coll), 30 sites with cortical
      (cort) porcine bone and 30 sites underwent natural healing. Primary (vertical and
      horizontal bone changes after 3 months) and secondary outcomes (histomorphometric
      after 3 months) were evaluated at implant placement. RESULTS: The vertical bone
      changes at the grafted sockets were significantly (p < 0.0001) lower (0.30 mm for
      cort group and 0.57 mm for coll group) when compared to non-grafted sockets (2.10
      mm for nat group). Moreover, the width reduction of the coll (0.93 mm) and cort
      (1.33 mm) groups was significantly lower (p < 0.0001) than the non-grafted group
      (3.60 mm). The analysis of subgroups attested that when premolar and molar sites
      were compared, the buccal bone loss appeared to be dependent both on tooth
      position and grafting material employed. CONCLUSION: The ridge preservation
      procedures had significantly better outcomes when compared to natural healing.
      The biomaterials did not differ for maintenance of bone width; even though, the
      bone height seemed to be better preserved with the cortical porcine bone.

PMID- 27883212
TI  - A retrospective study on periodontal disease progression in private practice.
AB  - BACKGROUND: Only a handful of studies have assessed tooth loss risk in chronic
      periodontitis patients following active therapy and factors associated with it.
      AIMS: The aim of this retrospective study was to assess tooth loss in a cohort of
      chronic periodontitis patients undergoing maintenance care in a UK private
      practice setting. MATERIALS AND METHODS: One hundred chronic periodontitis
      patients treated with active periodontal therapy were followed up in supportive
      periodontal therapy (SPT) for at least 5 years. Tooth loss rates and the effect
      of patient and tooth factors on tooth loss were assessed. Existing patient-based
      prognosis systems and a novel tooth-based prognosis system were tested for their
      association with tooth loss. RESULTS: Excluding third molars, 34 teeth were
      extracted during SPT, with an overall average tooth loss of 0.06
      teeth/patient/year (0.02 for periodontal reasons). Multivariable analysis showed
      that age, patient prognosis based on the Periodontal Risk Assessment system,
      tooth prognosis, furcation involvement and previous endodontic therapy were
      significantly associated with tooth loss during SPT. CONCLUSION: Good overall
      stability and a small tooth loss rate were observed in this cohort of chronic
      periodontitis cases under SPT in private practice. Patient-based and tooth-based
      prognosis systems may be used to estimate the risk of tooth loss.

PMID- 27883213
TI  - Oxidative Stress and Amyloid Toxicity: Insights From Yeast.
AB  - Alzheimer's disease is the most common neurodegenerative disorder. One of the
      factors that promotes neurodegeneration is the accumulation of senile plaques
      formed by Abeta peptide. In this paper, it was analyzed that if oxidative stress
      is cause or consequence of amyloid cascade and the role of antioxidant defense
      system in this process, using S. cerevisiae (with a multicopy plasmid containing
      the Abeta1-42 sequence) as experimental model. Cells grown on glycerol were more
      tolerant than when grown on glucose, strengthening the role of the antioxidant
      defense system against Abeta accumulation. Antioxidant defense deficiency did not
      change the pattern of amyloid aggregation. On the other hand, the presence of
      Abeta increased the level of intracellular oxidation and induced the activity of
      catalase, superoxide dismutase, and aconitase. Peroxissomal catalase deficient
      cells (Deltacta1), were more sensitive to Abeta toxicity than the wild type
      strain, while mitochondrial superoxide dismutase (Sod2) deficient cells displayed
      the highest frequency of petites. Besides, Abeta alters the oxygen consumption
      and the activity of complex III and IV. Taken together, our results point out
      that the Abeta toxicity mechanism involves an oxidative stress induction by
      increasing ROS production into the mitochondria, where Cta1 and Sod2 play a
      crucial role in the regulation of the redox balance. J. Cell. Biochem. 118: 1442
      1452, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883214
TI  - Psychiatric, Demographic, and Brain Morphological Predictors of Relapse After
      Treatment for an Alcohol Use Disorder.
AB  - BACKGROUND: Relapse in alcohol use disorders (AUD) is related to a complex
      interplay among multiple biological, psychiatric, psychological, and psychosocial
      factors, which may change dynamically during and after treatment. At treatment
      entry for AUD, morphological abnormalities in anterior frontal regions and the
      insula have been observed in those who ultimately relapse following treatment.
      The goal of this study was to determine whether anterior frontal and insula
      measures of brain thickness, surface area, and volume predict posttreatment
      drinking status (i.e., relapser or abstainer) over an extended period after
      outpatient treatment for AUD, while concurrently considering common psychiatric,
      psychological, and psychosocial factors previously associated with relapse.
      METHODS: Alcohol-dependent individuals (n = 129) were followed for 18 months
      after treatment to determine posttreatment drinking status (abstainers [n = 47]
      or relapsers [n = 82]). Brain morphometrics were derived from FreeSurfer.
      Receiver operating characteristic (ROC) curve analysis was used to identify the
      regional brain thickness, surface area, and volume (all scaled to intracranial
      volume), demographic, psychiatric, other substance use (e.g., cigarette smoking),
      and alcohol consumption variables, obtained at entry into treatment, that best
      predicted posttreatment drinking status. Survival analyses determined variables
      that were related to duration of abstinence after treatment. RESULTS: ROC
      analyses indicated that mood disorders, education, and volumes of the right
      caudal anterior cingulate cortex (ACC), right rostral ACC, and total right
      frontal gray matter were significant predictors of posttreatment drinking status.
      Among relapsers, survival analyses showed smokers and individuals with a comorbid
      medical condition relapsed earlier after treatment. Additionally, a greater
      frequency of smokers relapsed within 6 months of AUD treatment. CONCLUSIONS:
      Results reinforce that relapse in AUD is a function of multiple biological,
      psychiatric, psychological, and psychosocial factors. Effective treatment of
      depressive disorders and cigarette smoking concurrent with AUD-focused
      interventions may promote better treatment outcomes.

PMID- 27883216
TI  - Long Non-Coding RNA Uc.187 Is Upregulated in Preeclampsia and Modulates
      Proliferation, Apoptosis, and Invasion of HTR-8/SVneo Trophoblast Cells.
AB  - Among the preeclampsia-related long non-cording RNAs (lncRNAs) screened with a
      gene chip in our preliminary study, uc.187 attracted our attention because of its
      high conservation across different species and significant positive correlation
      with preeclampsia (PE). The literature and bioinformatics analysis suggested that
      lncRNA uc.187 might be associated with cell growth, invasion, and apoptosis. The
      expression of uc.187 in severe preeclamptic placentas (n = 31) and normal
      placentas (n = 18) was evaluated by real-time reverse transcription polymerase
      chain reaction (qRT-PCR). We constructed a silencing lentivirus vector (uc.187
      siRNA) to explore the biological function of uc.187 in the development and
      progression of HTR-8/SVneo trophoblast cells in vitro. Furthermore, we utilized
      CCK8 analysis, a transwell invasion assay, and flow cytometry to determine the
      role of uc.187 in the proliferation, invasion, and apoptosis of HTR-8/SVneo
      trophoblast cells. The proteins related to proliferation (PCNA, Ki67), invasion
      (MMP-2/-9 and TIMP-1), and apoptosis (caspase-3, Bcl-2) were evaluated with a
      Western blot assay. The results showed that there was an obvious upregulation of
      uc.187 expression in preeclamptic placental tissues. In addition, uc.187
      silencing enhanced cell proliferation and invasion and reduced the cellular
      apoptotic response. Taken together, our findings suggest for the first time that
      abnormal expression of lncRNA uc.187 may lead to the aberrant biological behavior
      of HTR-8/SVneo cells. Therefore, we propose uc.187 as a novel lncRNA molecule
      that might contribute to the development of PE and might represent a potential
      diagnostic and therapeutic target for this disease. J. Cell. Biochem. 118: 1462
      1470, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883215
TI  - Effects of concomitant immunomodulators on the pharmacokinetics, efficacy and
      safety of adalimumab in patients with Crohn's disease or ulcerative colitis who
      had failed conventional therapy.
AB  - BACKGROUND: Adalimumab is approved for use in patients with moderate to severe
      Crohn's disease (CD) or ulcerative colitis (UC) who have not achieved disease
      control with conventional therapies including corticosteroids and/or
      immunomodulators (IMM). AIM: To analyse six studies that examined efficacy,
      pharmacokinetics and safety of combination IMM/adalimumab therapy, compared with
      adalimumab monotherapy in patients with inadequate disease control on
      conventional therapy. METHODS: Patients with moderate to severe CD or UC from
      randomised, double-blind, placebo-controlled trials were analysed. Adalimumab was
      added to background therapy; patients were categorised as receiving adalimumab
      monotherapy (CD induction, n = 245, maintenance, n = 185; UC induction, n = 213,
      maintenance, n = 157) or combination therapy (CD induction, n = 139, maintenance,
      n = 139; UC induction, n = 140, maintenance, n = 100) according to baseline
      immunomodulator use. Efficacy was reported for the intent-to-treat populations
      from each study, with remission defined as CD activity index <150 for CD and Mayo
      score <=2 with no subscore >1 for UC. Safety was assessed via adverse events.
      RESULTS: The proportions of patients achieving remission were similar for
      adalimumab monotherapy and immunomodulator combination therapy in all studies.
      Median adalimumab concentrations at week 4 or 8 were numerically but not
      significantly higher with adalimumab combination therapy vs. monotherapy in the
      CD and UC studies respectively. Incidence and rate of adverse events was similar
      for adalimumab monotherapy and combination therapy. CONCLUSIONS: Post hoc
      analysis of six randomised, controlled trials demonstrated no efficacy benefits
      with immunomodulator/adalimumab combination therapy, compared with adalimumab
      monotherapy in CD and UC patients with inadequate disease control on conventional
      therapy; the safety of the two treatment approaches was comparable.

PMID- 27883217
TI  - Nitric oxide is involved in methane-induced adventitious root formation in
      cucumber.
AB  - Our previous studies revealed that methane (CH4 ) induces adventitious rooting in
      cucumber. However, the corresponding molecular mechanism is still elusive. In
      this work, we discovered that CH4 triggered the accumulation of nitric oxide (NO)
      and thereafter cucumber adventitious rooting, mimicking the inducing effects of
      sodium nitroprusside (SNP) and NONOate (two NO-releasing compounds). Above
      mentioned responses were sensitive to NO scavenger(s), showing that the
      accumulation of NO and adventitious root development were respectively impaired.
      Inhibitor test and biochemical analysis suggested that endogenous NO mainly
      produced by mammalian NO synthase-like enzyme and diamine oxidases (DAO), might
      be required for adventitious root formation elicited by CH4 . Molecular evidence
      confirmed that CH4 -mediated induction of several marker genes responsible for
      adventitious root development, including CsDNAJ-1, CsCDPK1, CsCDPK5, cell
      division-related gene CsCDC6, and two auxin signaling genes, CsAux22D-like and
      CsAux22B-like, was casually dependent on NO signaling. The possible involvement
      of S-nitrosylation during the mentioned CH4 responses was preliminarily
      illustrated. Taken together, through pharmacological, anatomical and molecular
      approaches, it is suggested that NO might be involved in CH4 -induced cucumber
      adventitious rooting, and CH4 -eliciated NO-targeted proteins might be partially
      modulated at transcriptional and post-translational levels. Our work may increase
      the understanding of the mechanisms underlying CH4 -elicited root organogenesis
      in higher plants.

PMID- 27883218
TI  - Tyrosine Phosphorylation of the Pioneer Transcription Factor FoxA1 Promotes
      Activation of Estrogen Signaling.
AB  - The pioneer transcription factor FoxA1 plays an important role in estrogen
      signaling by opening closed chromatin and promoting recruitment of the estrogen
      receptor to its target regions in DNA. In this study, we analyzed tyrosine
      phosphorylation of FoxA1 by the non-receptor-type tyrosine kinase c-Abl. c-Abl
      was shown to phosphorylate FoxA1 at multiple sites, especially in the N- and C
      terminal regions. Tyr429 and Tyr464 were identified as the major phosphorylation
      sites in the FoxA1 C-terminal region. The phosphomimetic and nonphosphorylatable
      FoxA1 mutants were generated by glutamic acid and phenylalanine substitutions at
      these tyrosine residues, respectively. The phosphomimetic FoxA1 promoted the
      activation of estrogen signaling, whereas the nonphosphorylatable FoxA1
      suppressed its activation. Stimulation with the epidermal growth factor, which
      activates c-Abl, enhanced the activation of estrogen signaling. In contrast, the
      c-Abl inhibitor imatinib reduced its activation. The phosphomimetic FoxA1 mutant
      showed a higher affinity toward histone H3 than the wild-type. These results
      suggest that c-Abl-mediated phosphorylation of FoxA1 promotes the activation of
      estrogen signaling by inducing its binding to histones. J. Cell. Biochem. 118:
      1453-1461, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883220
TI  - How long does the volumizing effect of a Zingiber officinale-based lip plumper
      last?
AB  - OBJECTIVE: Lip plumpers should enhance lip volume. It has been shown that no
      noticeable result was obtained after long term use of these products. The present
      study has been carried out to assess lip plumpers' short term effectiveness
      within 2 h from application. METHODS: Effectiveness was assessed using non
      invasive techniques. The effect on vascularisation was analyzed with the
      Mexameter MX 16(r) , and the volume enhancing effect was assessed by
      anthropometric measures and profilometry analysis from 3D scanning electron
      microscope (SEM) images using Alicona's MEX software. Sixty female volunteers
      were recruited for the study and the measurements were taken 15, 30, 60, 90 and
      120 min after product application. RESULTS: Product application produced a
      statistically significant increase of lip vascularisation during the first 15
      min, which stayed unchanged until the 30th min, then decreased in intensity. The
      volumizing effect was revealed by 3D profilometry analysis only, not by
      anthropological measurements. The use of 3D SEM images showed an increase of 0.50
      mm in the protrusion of the lip vermilion (MHP parameter) during the first 15 min
      from product application. CONCLUSION: Results suggest that the lip plumper
      temporarily enhances vasodilation and increases lip volume.

PMID- 27883219
TI  - Drugs, Sex, and Condoms: Identification and Interpretation of Race-Specific
      Cultural Messages Influencing Black Gay and Bisexual Young Men Living with HIV.
AB  - Black gay and bisexual young men carry a disproportionate burden of HIV in the
      United States. This study explored Black gay and bisexual young men living with
      HIV's identification and interpretation of race-specific cultural messages
      regarding substance use, sexual activity, and condom use. A total of 36 Black gay
      and bisexual young men living with HIV (ages 16-24, mean = 20.6 years) from four
      geographically diverse regions of the United States participated in qualitative
      in-depth interviews. Results from this study elucidate the ways in which these
      young men interpret various forms of race-specific cultural messages and
      experiences regarding substance use, sexual activity, and condom use.
      Participants discussed cultural messages and experiences promoting and
      discouraging condoms and substance use. Regarding sexual activity, only messages
      and experiences promoting sex were reported. Across all three categories,
      messages and experiences promoting risk were predominant. Data further revealed
      that socially transmitted cultural messages received by young men emanated from
      multiple sources, such as family, peers, sexual partners, community/neighborhood,
      and the broader society. Race-specific cultural messages and experiences should
      be addressed in interventions for this population, and programs should assist
      young men in developing a critical consciousness regarding these messages and
      experiences in order to promote health and well-being.

PMID- 27883221
TI  - Alcohol Exposure Causes Overexpression of Heart Development-Related Genes by
      Affecting the Histone H3 Acetylation via BMP Signaling Pathway in Cardiomyoblast
      Cells.
AB  - BACKGROUND: Abusive alcohol utilization of pregnant woman may cause congenital
      heart disease (CHD) of fetus, where alcohol ignites histone H3 hyperacetylation
      leading to abnormal development of heart morphogenesis and associated genes.
      Knowledge about the regularized upstream genes is little, but bone morphogenetic
      protein (BMP) signaling may actively and prominently take part in alteration in
      acetylation of histone H3. The supreme objective of this study was to unearth the
      involvement of BMP signaling pathway in alcohol-driven hyperacetylation of
      histone H3 in cardiomyoblast cells. METHODS: Cardiomyoblast cells (H9c2 cells)
      were addicted with alcohol (100 mM) for 24 hours. Dorsomorphin (5 MUM) was used
      for the inhibition of BMP signaling pathway. We detected the phosphorylation
      activity of SMAD1/5/8, mRNA expression, histone acetyltransferases (HAT)/histone
      deacetylase (HDAC) activity, and acetylation of histone H3. RESULTS: Following
      alcohol exposure, phosphorylation of SMAD1/5/8 and HAT activities was increased
      to a significant extent, while histone H3 acetylation and expression of heart
      development-related genes were also increased. The said phenomenon influenced by
      alcohol was reverted upon dorsomorphin treatment to the cells without effecting
      HDAC activity. CONCLUSIONS: The data clearly identified that BMP-mediated histone
      H3 acetylation of heart development-related genes might be one of the possible
      cellular mechanisms to control alcohol-induced expression of heart development
      related genes. Dorsomorphin, on the other hand, may modulate alcohol-induced
      hyperacetylation of histone H3 through BMP targeting, which could be a potential
      way to block CHD.

PMID- 27883223
TI  - Mannitol biosynthesis in algae: more widespread and diverse than previously
      thought.

PMID- 27883224
TI  - Basic Fibroblast Growth Factor Regulates REX1 Expression Via IL-6 In Stem Cells
      Isolated From Human Exfoliated Deciduous Teeth.
AB  - Basic fibroblast growth factor (bFGF) regulates pluripotent marker expression and
      cellular differentiation in various cell types. However, the mechanism by which
      bFGF regulates REX1 expression in stem cells, isolated from human exfoliated
      deciduous teeth (SHEDs) remains unclear. The aim of the present study was to
      investigate the regulation of REX1 expression by bFGF in SHEDs. SHEDs were
      isolated and characterized. Their mRNA and protein expression levels were
      determined using real-time polymerase chain reaction and enzyme-linked
      immunosorbent assay, respectively. In some experiments, chemical inhibitors were
      added to the culture medium to impede specific signaling pathways. Cells isolated
      from human exfoliated deciduous tooth dental pulp tissue expressed mesenchymal
      stem cell surface markers (CD44, CD73, CD90, and CD105). These cells
      differentiated into osteogenic and adipogenic lineages, when appropriately
      induced. Treating SHEDs with bFGF induced REX1 mRNA expression and this effect
      was attenuated by pretreatment with FGFR or Akt inhibitors. Cycloheximide
      pretreatment also inhibited the bFGF-induced REX1 expression, implying the
      involvement of intermediate molecule(s). Further, the addition of an IL-6
      neutralizing antibody attenuated the bFGF-induced REX1 expression by SHEDs. In
      conclusion, bFGF enhanced REX1 expression by SHEDs via the FGFR and Akt signaling
      pathways. Moreover, IL-6 participated in the bFGF-induced REX1 expression in
      SHEDs. J. Cell. Biochem. 118: 1480-1488, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883222
TI  - Alcohol Misuse and Co-Occurring Mental Disorders Among New Soldiers in the U.S.
      Army.
AB  - BACKGROUND: Problem drinking that predates enlistment into military service may
      contribute to the overall burden of alcohol misuse in the Armed Forces; however,
      evidence bearing on this issue is limited. This study examines prevalence and
      correlates of alcohol misuse among new U.S. Army soldiers. METHODS: Cross
      sectional survey data were collected from soldiers reporting for basic combat
      training. The survey retrospectively assessed lifetime alcohol consumption and
      substance abuse/dependence, enabling estimation of the prevalence of lifetime
      binge drinking and heavy drinking in a sample of 30,583 soldiers and of probable
      alcohol use disorder (AUD) among 26,754 soldiers with no/minimal lifetime use of
      other drugs. Co-occurrence of mental disorders and other adverse outcomes with
      binge drinking, heavy drinking, and AUD was examined. Discrete-time survival
      analysis, with person-year the unit of analysis and a logistic link function, was
      used to estimate associations of AUD with subsequent onset of mental disorders
      and vice versa. RESULTS: Weighted prevalence of lifetime binge drinking was 27.2%
      (SE = 0.4) among males and 18.9% (SE = 0.7) among females; respective estimates
      for heavy drinking were 13.9% (SE = 0.3) and 9.4% (SE = 0.4). Among soldiers with
      no/minimal drug use, 9.5% (SE = 0.2) of males and 7.2% (SE = 0.5) of females had
      lifetime AUD. Relative to no alcohol misuse, binge drinking, heavy drinking, and
      AUD were associated with increased odds of all mental disorders and other adverse
      outcomes under consideration (adjusted odds ratios [AORs] = 1.5 to 4.6; ps <
      0.001). Prior mental disorders and suicidal ideation were associated with onset
      of AUD (AORs = 2.3 to 2.8; ps < 0.001), and prior AUD was associated with onset
      of mental disorders and suicidal ideation (AORs = 2.0 to 3.2, ps < 0.005).
      CONCLUSIONS: Strong bidirectional associations between alcohol misuse and mental
      disorders were observed in a cohort of soldiers beginning Army service. Conjoint
      recognition of alcohol misuse and mental disorders upon enlistment may provide
      opportunities for risk mitigation early in a soldier's career.

PMID- 27883225
TI  - Computational Screening and Exploration of Disease-Associated Genes in
      Alzheimer's Disease.
AB  - Alzheimer's is a neurodegenerative disease affecting large populations worldwide
      characterized mainly by progressive loss of memory along with various other
      symptoms. The foremost cause of the disease is still unclear, however various
      mechanisms have been proposed to cause the disease that include amyloid
      hypothesis, tau hypothesis, and cholinergic hypothesis in addition to genetic
      factors. Various genes have been known to be involved which are APOE, PSEN1,
      PSEN2, and APP among others. In the present study, we have used computational
      methods to examine the pathogenic effects of non-synonymous single nucleotide
      polymorphisms (SNPs) associated with ABCA7, CR1, MS4A6A, CD2AP, PSEN1, PSEN2, and
      APP genes. The SNPs were obtained from dbSNP database followed by identification
      of deleterious SNPs and prediction of their functional impact. Prediction of
      disease-associated mutations was performed and the impact of the mutations on the
      stability of the protein was carried out. To study the structural significance of
      the computationally prioritized mutations on the proteins, molecular dynamics
      simulation studies were carried out. On analysis, the SNPs with IDs rs76282929
      ABCA7; CR1 rs55962594; MS4A6A rs601172; CD2AP rs61747098; PSEN1 rs63750231,
      rs63750265, rs63750526, rs63750577, rs63750687, rs63750815, rs63750900,
      rs63751037, rs63751163, rs63751399; PSEN2 rs63749851; and APP rs63749964,
      rs63750066, rs63750734, and rs63751039 were predicted to be deleterious and
      disease-associated having significant structural impact on the proteins. The
      current study proposes a precise computational methodology for the identification
      of disease-associated SNPs. J. Cell. Biochem. 118: 1471-1479, 2017. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27883226
TI  - The Circadian Gene Clock Regulates Bone Formation Via PDIA3.
AB  - The expression patterns of clock-controlled genes (ccgs) are regulated by
      circadian rhythm, which is a major regulatory and physiological mechanism tied to
      the solar day. Disruptions in circadian rhythm contribute to the development of
      cardiovascular diseases, cancer, metabolic syndromes, and aging. It has been
      reported that bone remodeling is also regulated by circadian rhythm. However, the
      molecular mechanism by which the circadian gene Clock regulates bone remodeling
      has yet to be elucidated. Here, we show that Clock mutant mice exhibit a
      significant reduction in bone density as well as increased apoptosis. Protein
      disulfide isomerase family A member 3 (PDIA3) is a 1,25-dihydroxy-vitamin D3
      [1alpha,25(OH)2D3] receptor that can regulate bone formation and apoptosis. Using
      luciferase and ChIP assays, we confirmed that Pdia3 is a ccg. Clock activates
      Pdia3 transcription by binding the E-box promoter, and transcription is decreased
      in ClockDelta19 mutant mice. Forced expression of Pdia3 or of Clock completely
      rescues the osteogenic disorders found in the mutant background and inhibits
      apoptosis in vivo and in vitro. Furthermore, ablation of PDIA3 via RNA
      interference completely blocks the compensatory effect of forced expression of
      Clock in osteoblasts. Our results demonstrate that the core circadian gene Clock
      regulates bone formation via transcriptional control of 1,2,5(OH)2D3 receptor
      PDIA3. (c) 2016 American Society for Bone and Mineral Research.

PMID- 27883228
TI  - In grateful recognition of our Editorial Board.

PMID- 27883227
TI  - Preterm infants exhibited less pain during a heel stick when they were played the
      same music their mothers listened to during pregnancy.
AB  - AIM: Playing music during painful procedures has shown inconsistent benefits for
      preterm infants. This study observed preterm infants during a heel stick
      procedure to assess whether listening to the music their mothers listened to
      during pregnancy had any impact on their pain and physiological and behavioural
      parameters. METHODS: We randomly exposed 42 preterm infants, with a mean
      gestational age of 31.8 +/- 2.79 weeks, to the music their mothers listened to
      during pregnancy, recorded lullabies and no music, before, during and after a
      heel stick. Pain responses were measured using the Neonatal Pain, Agitation and
      Sedation Scale (N-PASS), and physiological and behavioural responses were
      recorded by a nurse blinded to the intervention. RESULTS: N-PASS pain scores were
      lowest during mothers' music, with a mean of 1.40 (+/-1.28), compared to 2.33 (+/
      1.64) for no music and 1.62 (+/-2.27) for the lullabies [F(3/121) = 4.86, p =
      0.009]. Physiological parameters were not significantly different between the
      conditions. During the mothers' music, infants spent more time in a quiet alert
      state, with a significant decrease in their respiratory rates. CONCLUSION: The
      music mothers listened to during pregnancy was more beneficial for preterm
      infants, as it decreased pain and improved behavioural states during a heel
      stick.

PMID- 27883229
TI  - What's in a Discussion section? Exploiting 2-dimensionality in the online
      world....

PMID- 27883230
TI  - Missing heritability: Illegitimate quantitative comparison of holistic and
      reductionist data (response to DOI 10.1002/bies.201600084).

PMID- 27883231
TI  - Evaluating the credibility of histopathology data in environmental endocrine
      toxicity studies.
AB  - Agencies responsible for environmental protection are tasked with developing
      regulatory guidance that is based on the best available scientific evidence.
      Histopathology is a common endpoint in toxicologic bioassays; however, because of
      the subjective nature of this endpoint, and the advanced level of specialized
      training required for its effective utilization, the reliability of
      histopathology data can be inconsistent. Consequently, mechanisms for evaluating
      such data on a case-by-case basis are needed. The purposes of the present review
      are to describe a methodology that can be used to evaluate the credibility of
      histopathology findings and to discuss the results of such assessments as applied
      to real-world data collected from the scientific literature. A key outcome of
      these efforts was the finding that only 54% of the studies examined contained
      histopathology data that were considered to be either highly credible or
      credible, whereas data in 46% of those studies were of equivocal, dubious, or no
      credibility. In addition, the results indicated that the quality of the data
      examined tended to decline during the past 15 yr. The ultimate goals of the
      present review are to draw attention to reliability issues that can affect
      histopathology results, provide recommendations to improve the quality of this
      endpoint, and suggest an approach for the expeditious and judicious use of
      histopathology data in the weight-of-evidence determinations required for hazard
      and/or risk assessment. This exercise was conducted initially as part of a SETAC
      Pellston WorkshopTM entitled "Environmental Hazard and Risk Assessment Approaches
      for Endocrine-Active Chemicals (EHRA): Developing Technical Guidance Based on
      Case Studies to Support Decision Making" that was held in Pensacola, Florida
      (USA) from 31 January to 5 February 2016. Environ Toxicol Chem 2017;36:601-611.
      (c) 2016 SETAC.

PMID- 27883232
TI  - Primary sources and toxicity of PAHs in Milwaukee-area streambed sediment.
AB  - High concentrations of polycyclic aromatic hydrocarbons (PAHs) in streams can be
      a significant stressor to aquatic organisms. To understand the likely sources and
      toxicity of PAHs in Milwaukee-area streams, streambed sediment samples from 40
      sites and parking lot dust samples from 6 sites were analyzed for 38 parent PAHs
      and 25 alkylated PAHs. Diagnostic ratios, profile correlations, principal
      components analysis, source-receptor modeling, and mass fractions analysis were
      used to identify potential PAH sources to streambed sediment samples, and land
      use analysis was used to relate streambed sediment PAH concentrations to
      different urban-related land uses. On the basis of this multiple lines-of
      evidence approach, coal-tar pavement sealant was indicated as the primary source
      of PAHs in a majority of streambed sediment samples, contributing an estimated
      77% of total PAHs to samples, on average. Comparison with the probable effect
      concentrations and (or) the equilibrium partitioning sediment benchmark indicates
      that 78% of stream sediment samples are likely to cause adverse effects to
      benthic organisms. Laboratory toxicity tests on a 16-sample subset of the
      streambed sites using the amphipod Hyalella azteca (28-d) and the midge
      Chironomus dilutus (10-d) measured significant reductions in 1 or more biological
      endpoints, including survival, in 75% of samples, with H. azteca more responsive
      than C. dilutus. Environ Toxicol Chem 2017;36:1622-1635. (c) 2016 The Authors.
      Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on
      behalf of SETAC.

PMID- 27883234
TI  - Stereospecific Synthesis of Fluoroalkenes by Silver-Mediated Fluorination of
      Functionalized Alkenylstannanes.
AB  - The known procedures for the conversion of alkenylstannanes into the
      corresponding fluoroalkenes suffer from largely variable yields and a limited
      compatibility with functional groups; most notably, protodestannation becomes a
      serious issue whenever protic sites are present in the substrate. Outlined in
      this paper is a convenient alternative with a much improved application profile,
      which is largely unperturbed by free alcohols and amides of all sorts. Key to
      success is the use of F-TEDA-PF6 in combination with non-hygroscopic and bench
      stable silver phosphinate (AgOP(O)Ph2 ) that acts as an essentially neutral, non
      nucleophilic promotor and effective tin-scavenger at the same time. This new
      method opens many opportunities for late-stage fluorination of elaborate
      compounds far beyond the scope of the literature procedures, as witnessed by the
      preparation of a fluorinated macrolide antibiotic, a fluorinated prostaglandin
      derivative, and a set of fluorinated amino acid surrogates and peptide isosteres.

PMID- 27883233
TI  - Intranasal Insulin Boosts Gustatory Sensitivity.
AB  - Intranasal insulin has been the subject of attention not only with respect to
      enhancing memory processes, but also for its anorexic effects, as well as its
      effects on olfactory sensitivity. In the present study, the influence of
      intranasal insulin on gustatory sensitivity was investigated using intranasal
      applications of insulin or placebo in a double-blind manner alongside a control
      condition without any application. We hypothesised that, because it mediates
      satiety, intranasal insulin alters gustatory sensitivity, whereas placebo
      application and the control should not alter gustatory sensitivity. We did not
      expect the sensitivity to the different taste solutions to differ. Sweet, salty,
      bitter and sour liquids in four concentrations each were sprayed onto the tongue
      of healthy male subjects. Additionally, water with no taste was applied to enable
      calculation of taste sensitivity in terms of parameter d' of signal detection
      theory. The task of the subject was to identify the quality of the respective
      tastant. Gustatory sensitivity and blood parameters were evaluated using repeated
      measures ANOVAs. Gustatory sensitivity (implying all tastants) improved
      significantly after intranasal insulin application compared to the application of
      placebo, although it did not reach significance compared to the control
      condition. Subjects performed best when detecting the sweet taste and worst when
      detecting the bitter taste. The blood parameters glucose, insulin, homeostatic
      model assessment and leptin did not differ with respect to insulin or placebo
      condition, nor did they differ regarding measurements preceding or following
      intranasal application, in confirmation of preserved peripheral euglycaemia
      during the experiment. Thus, it can be concluded that the application of
      intranasal insulin led to an improved gustatory sensitivity compared to placebo.

PMID- 27883235
TI  - Genomewide association study of peanut allergy reproduces association with amino
      acid polymorphisms in HLA-DRB1.
AB  - BACKGROUND: Genetic variants for IgE-mediated peanut allergy are yet to be fully
      characterized and to date only one genomewide association study (GWAS) has been
      published. OBJECTIVE: To identify genetic variants associated with challenge
      proven peanut allergy. METHODS: We carried out a GWAS comparing 73 infants with
      challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants
      (all ~ 1 year old). We tested a total of 3.8 million single nucleotide
      polymorphisms, as well as imputed HLA alleles and amino acids. Replication was
      assessed by de novo genotyping in a panel of additional 117 cases and 380
      controls, and in silico testing in two independent GWAS cohorts. RESULTS: We
      identified 21 independent associations at P <= 5 * 10-5 but were unable to
      replicate these. The most significant HLA association was the previously reported
      amino acid variant located at position 71, within the peptide-binding groove of
      HLA-DRB1 (P = 2 * 10-4 ). Our study therefore reproduced previous findings for
      the association between peanut allergy and HLA-DRB1 in this Australian
      population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for
      challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.

PMID- 27883237
TI  - Iron concentration in breast milk normalised within one week of a single high
      dose infusion of iron isomaltoside in randomised controlled trial.
AB  - AIM: We compared the iron concentration in breast milk after a single high dose
      of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage.
      METHODS: In this randomised controlled trial, the women were allocated a single
      dose of intravenous 1200 mg iron isomaltoside or oral iron at a mean daily dose
      of 70.5 mg. We included 65 women with sufficient breast milk three days after
      inclusion - 30 from the intravenous iron group and 35 from the oral iron group -
      and collected breast milk and maternal blood samples three days and one week
      after allocation. RESULTS: The mean (+/-SD) iron concentration in breast milk in
      the intravenous and oral groups was 0.72 +/- 0.27 and 0.40 +/- 0.18 mg/L at three
      days (p < 0.001) and 0.47 +/- 0.17 and 0.44 +/- 0.25 mg/L after one week (p =
      0.64). Baseline samples were not available that soon after birth. CONCLUSION: A
      single high dose of intravenous iron isomaltoside for postpartum haemorrhage led
      to a transient increase in the iron concentration in breast milk three days after
      treatment compared with oral iron. The difference disappeared one week after
      treatment, and mean iron concentrations were within the normal range in all
      samples.

PMID- 27883236
TI  - Long-term reduction in food allergy susceptibility in mice by combining
      breastfeeding-induced tolerance and TGF-beta-enriched formula after weaning.
AB  - BACKGROUND: Oral tolerance induction in early life is a promising approach for
      food allergy prevention. Its success requires the identification of factors
      necessary for its persistence. OBJECTIVES: We aimed to assess in mice duration of
      allergy prevention by breastfeeding-induced oral tolerance and whether oral TGF
      beta supplementation after weaning would prolong it. METHODS: We quantified
      ovalbumin (OVA) and OVA-specific immunoglobulin levels by ELISA in milk from the
      EDEN birth cohort. As OVA-specific Ig was found in all samples, we assessed
      whether OVA-immunized mice exposed to OVA during lactation could prevent allergic
      diarrhoea in their 6- and 13-week-old progeny. In some experiments, a TGF-beta
      enriched formula was given after weaning. RESULTS: At 6 weeks, only 13% and 34%
      of mice breastfed by OVA-exposed mothers exhibited diarrhoea after six and seven
      OVA challenges vs. 44% and 72% in mice breastfed by naive mothers (P = 0.02 and
      0.01). Protection was associated with decreased levels of MMCP1 and OVA-specific
      IgE (P < 0.0001). At 13 weeks, although OVA-specific IgE remained low (P =
      0.001), diarrhoea occurrence increased to 32% and 46% after six and seven OVA
      challenges in mice breastfed by OVA-exposed mothers. MMCP1 levels were not
      significantly inhibited. Supplementation with TGF-beta after weaning induced a
      strong protection in 13-week-old mice breastfed by OVA-exposed mothers compared
      with mice breastfed by naive mothers (0%, 13% and 32% of diarrhoea at the fifth,
      sixth and seventh challenges vs. 17, 42 and 78%; P = 0.05, 0.0043 and 0.0017).
      MMCP1 levels decreased by half compared with control mice (P = 0.02). Prolonged
      protection was only observed in mice rendered tolerant by breastfeeding and was
      associated with an improved gut barrier. CONCLUSIONS: In mice, prevention of food
      allergy by breastfeeding-induced tolerance is of limited duration. Nutritional
      intervention by TGF-beta supplementation after weaning could prolong beneficial
      effects of breast milk on food allergy prevention.

PMID- 27883238
TI  - Striking Doping Effects on Thermal Methane Activation Mediated by the
      Heteronuclear Metal Oxides [XAlO4 ].+ (X=V, Nb, and Ta).
AB  - The thermal reactivity of the heteronuclear metal-oxide cluster cations [XAlO4
      ].+ (X=V, Nb, and Ta) towards methane has been studied by using mass spectrometry
      in conjunction with quantum mechanical calculations. Experimentally, a hydrogen
      atom transfer (HAT) from methane is mediated by all the three oxide clusters at
      ambient conditions. However, [VAlO4 ].+ is unique in that this cluster directly
      transforms methane into formaldehyde. The absence of this reaction for the Nb and
      Ta analogues demonstrates a striking doping effect on the chemoselectivity in the
      conversion of methane. Mechanistic aspects of the two reactions have been
      elucidated by quantum-chemical calculations. The HAT reactivity can be attributed
      to the significant spin density localized at the terminal oxygen atom (Ot.- ) of
      the cluster ions, while the ionic/covalent character of the Lewis acid-base unit
      [X-Ob ] plays a crucial role for the generation of formaldehyde. The mechanistic
      insight derived from this combined experimental/computational investigation may
      provide guidance for a more rational design of catalysts.

PMID- 27883240
TI  - Diagnosing occupational asthma.
AB  - Making an accurate diagnosis of occupational asthma (OA) is, generally,
      important. The condition has not only significant health consequences for
      affected workers, but also substantial socio-economic impacts for workers, their
      employers and wider society. Missing a diagnosis of OA may lead to continued
      exposure to a causative agent and progressive worsening of disease; conversely,
      diagnosing OA when it is not present may lead to inappropriate removal from
      exposure and unnecessary financial and social consequences. While the most
      accurate investigation is specific inhalation challenge in an experienced centre,
      this is a scarce resource, and in many cases, reliance is on other tests. This
      review provides a technical dossier of the diagnostic value of the available
      methods which include an appropriate clinical history, the use of specific
      immunology and measurement of inflammatory markers, and various methods of
      relating functional changes in airway calibre to periods at work. It is
      recommended that these approaches are used iteratively and in judicious
      combination, in cognizance of the individual patient's circumstances and
      requirements. Based on available evidence, a working diagnostic algorithm is
      proposed that can be adapted to the suspected agent, purpose of diagnosis and
      available resources. For better or worse, many of the techniques - and their
      interpretation - are available only in specialized centres and where there is
      room for doubt, referral to such a centre is probably wise. Accordingly, the
      implementation or development of such specialized centres with appropriate
      equipment and expertise should greatly improve the diagnostic evaluation of work
      related asthma.

PMID- 27883239
TI  - Individually dosed omalizumab: an effective treatment for severe peanut allergy.
AB  - BACKGROUND: Treatment with omalizumab has shown a positive effect on food
      allergies, but no dosages are established. Basophil allergen threshold
      sensitivity (CD-sens) can be used to objectively measure omalizumab treatment
      efficacy and correlates with the outcome of double-blind placebo-controlled food
      challenge to peanut. OBJECTIVE: To evaluate whether individualized omalizumab
      treatment monitored by CD-sens could be an effective intervention for suppression
      of allergic reactions to peanut. METHODS: Severely peanut allergic adolescents (n
      = 23) were treated with omalizumab for 8 weeks, and CD-sens was analysed before
      and after. Based on whether CD-sens was suppressed after 8 weeks, the patients
      either were subject to a peanut challenge or received eight more weeks with
      increased dose of omalizumab, followed by peanut challenge or another 8-week
      cycle of omalizumab. IgE and IgE-antibodies to peanut and its components were
      analysed before treatment. RESULTS: After individualized omalizumab treatment (8
      24 weeks), all patients continued with an open peanut challenge with no (n = 18)
      or mild (n = 5) objective allergic symptoms. Patients (n = 15) needing an
      elevated omalizumab dose (ED) to suppress CD-sens had significantly higher CD
      sens values at baseline 1.49 (0.44-20.5) compared to those (n = 8) who managed
      with normal dose (ND) 0.32 (0.24-5.5) (P < 0.01). Median ratios for Ara h 2 IgE
      ab/IgE were significantly higher in the ED group (17%) compared to the ND group
      (11%). CONCLUSIONS AND CLINICAL RELEVANCE: Individually dosed omalizumab,
      monitored by CD-sens, is an effective and safe treatment for severe peanut
      allergy. The ratio of IgE-ab to storage protein Ara h 2/IgE as well as CD-sens to
      peanut may predict the need of a higher omalizumab dose. Clinical trials numbers:
      EudraCT; 2012-005625-78, ClinicalTrials.gov; NCT02402231.

PMID- 27883241
TI  - Neutrophil autophagy and extracellular DNA traps contribute to airway
      inflammation in severe asthma.
AB  - BACKGROUND: Autophagy and neutrophil extracellular DNA traps (NETs) are
      implicated in asthma; however, their roles in asthma pathogenesis have not been
      elucidated. OBJECTIVES: We compared autophagy and NET production levels from
      peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non
      severe asthma (NSA). Additionally, we investigated the inflammatory effects of
      NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils
      (PBEs). METHODS: Peripheral blood neutrophils from patients with SA (n = 30) and
      NSA (n = 38) were treated with interleukin (IL)-8 (100 ng/mL). Autophagy (light
      chain 3-II expression) and NET production levels were evaluated by Western blot,
      immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs
      were assessed by investigating cell death, cell detachment, expression of
      occludin and claudin-1, and IL-8 production; the effects of NETs on PBEs were
      examined by investigating the activation and release of eosinophil cationic
      protein (ECP) and eosinophil-derived neurotoxin (EDN). RESULTS: Untreated and IL
      8-treated PBNs from the SA group produced higher autophagy and NET levels
      compared with those from the NSA group (P < 0.01). IL-8 increased autophagy and
      NET levels in PBNs from the SA group, but not from the NSA group. NET levels were
      correlated with autophagy levels in PBNs (P < 0.001). IL-8-induced NET production
      levels negatively were correlated with FEV1/FVC (r = -0.700, P = 0.016). NETs
      induced cell death, detachment, degradation of occludin and claudin-1, and IL-8
      production from AECs. Higher levels of NET-induced ECP and EDN were released from
      PBEs in SA compared with NSA groups. CONCLUSIONS AND CLINICAL RELEVANCE:
      Neutrophil autophagy and NETs could enhance asthma severity by damaging airway
      epithelium and triggering inflammatory responses of AECs and PBEs. Modulating
      neutrophil autophagy and NET production may be a new target therapy for SA.

PMID- 27883243
TI  - Alternative Mechanistic Strategy for Enzyme Catalysis in a Ni-Dependent Lactate
      Racemase (LarA): Intermediate Destabilization by the Cofactor.
AB  - Recently, a lactate racemase was discovered as a new Ni-dependent enzyme with a
      unique tethered NAD-like cofactor. We report the first computational study aimed
      at deciphering the previously unclear role of the Ni-tethered cofactor in
      reactions of the lactate racemase. Our calculations revealed that the cofactor
      increases the dehydrogenation barriers. The formation of a metastable NADH-like
      pyruvate intermediate and two nearby histidine bases are proposed as the key
      factors in the racemization reaction. Such destabilization of intermediates by
      the cofactor is uncommon in enzymatic catalysis. This result provides new insight
      into the design of a reactive metal-tethered NADH-like complex for synthetic
      hydrogenations.

PMID- 27883244
TI  - A Redox-Switchable Germylene and its Ligating Properties in Selected Transition
      Metal Complexes.
AB  - The synthesis, structure, and full characterization of a redox-switchable
      germylene based on a [3]ferrocenophane ligand arrangement, [Fc(NMes)2 Ge] (4), is
      presented. The mesityl (Mes)-substituted title compound is readily available from
      Fc(NHMes)2 (2) and Ge{N(SiMe3 )2 }2 , or from the dilithiated, highly air- and
      moisture-sensitive compound Fc(NLiMes)2 ?3 Et2 O (3) and GeCl2 . Cyclic
      voltammetry studies are provided for 4, confirming the above-mentioned view of a
      redox-switchable germylene metalloligand. Although several 1:1 RhI and IrI
      complexes of 4 (5-7) are cleanly formed in solution, all attempts to isolate them
      in pure form failed due to stability problems. However, crystalline solids of
      [Mo(kappa1 Ge-4)2 (CO)4 ] (8) and [W(kappa1 Ge-4)2 (CO)4 ] (9) were isolated and
      fully characterized by common spectroscopic techniques (8 by X-ray diffraction).
      DFT calculations were performed on a series of model compounds to elucidate a
      conceivable interplay between the metal atoms in neutral and cationic bimetallic
      complexes of the type [Rh(kappa1 E-qE)(CO)2 Cl]0/+ (qE=[Fc(NPh)2 E] with E=C, Si,
      Ge). The bonding characteristics of the coordinated Fc-based metalloligands
      (qE/qE+ ) are strongly affected upon in silico oxidation of the calculated
      complexes. The calculated Tolman electronic parameter (TEP) significantly
      increases by approximately 20 cm-1 (E=C) to 25 cm-1 (E=Si, Ge) upon oxidation.
      The change in the ligand-donating abilities upon oxidation can mainly be
      attributed to Coulombic effects, whereas an orbital-based interaction appears to
      have only a minor influence.

PMID- 27883245
TI  - A Prediction of Proton-Catalyzed Hydrogenation of Ketones in Lewis Basic Solvent
      through Facile Splitting of Hydrogen Molecules.
AB  - A ketone's carbonyl carbon is electrophilic and harbors a part of the lowest
      unoccupied molecular orbital of the carbonyl group, resembling a Lewis acidic
      center; under the right circumstances it exhibits very useful chemical
      reactivity, although the natural electrophilicity of the ketone's carbonyl carbon
      is often not strong enough on its own to produce such reactivity. Quantum
      chemical calculations predict that a proton shared between a ketone and the Lewis
      basic solvent molecule (dioxane or THF) activates carbonyl carbon to the point of
      enabling a facile heterolytic splitting of H2 . Proton-catalyzed hydrogenation of
      a ketone in Lewis basic solvent is the result. The mechanism involves the
      interaction of H2 with the enhanced Lewis acidity of a carbonyl carbon and the
      free Lewis basic solvent molecule polarizes H2 and enables the hydride-type
      attack on carbonyl carbon, which is very strongly influenced by the proton shared
      between a ketone and solvent. The hydride-type attack on carbon is reminiscent of
      the splitting of H2 by singlet carbenes except that, in this case, a Lewis base
      from the surrounding environment (solvent) is necessary for polarization of H2
      and acceptance of the proton resulting from the heterolytic splitting of H2 .

PMID- 27883242
TI  - sFlt-1/PlGF for prediction of early-onset pre-eclampsia: STEPS (Study of Early
      Pre-eclampsia in Spain).
AB  - OBJECTIVE: A high ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to
      placental growth factor (PlGF) has been linked to pre-eclampsia (PE). We
      evaluated the sFlt-1/PlGF ratio as a predictive marker for early-onset PE in
      women at risk of PE. METHODS: This prospective, Spanish, multicenter study
      included pregnant women with a risk factor for PE, including intrauterine growth
      restriction, PE, eclampsia or hemolysis, elevated liver enzymes and low platelet
      count syndrome in previous pregnancy, pregestational diabetes or abnormal uterine
      artery Doppler. The primary objective was to show that the sFlt-1/PlGF ratio at
      20, 24 and 28 weeks' gestation was predictive of early-onset PE (< 34 + 0 weeks).
      Serum sFlt-1 and PlGF were measured at 20, 24 and 28 weeks. Multivariate logistic
      regression was used to develop a predictive model. RESULTS: A total of 819 women
      were enrolled, of which 729 were suitable for analysis. Of these, 78 (10.7%)
      women developed PE (24 early onset and 54 late onset). Median sFlt-1/PlGF ratio
      at 20, 24 and 28 weeks was 6.3 (interquartile range (IQR), 4.1-9.3), 4.0 (IQR,
      2.6-6.3) and 3.3 (IQR, 2.0-5.9), respectively, for women who did not develop PE
      (controls); 14.5 (IQR, 5.5-43.7), 18.4 (IQR, 8.2-57.9) and 51.9 (IQR, 11.5-145.6)
      for women with early-onset PE; and 6.7 (IQR, 4.6-9.9), 4.7 (IQR, 2.8-7.2) and 6.0
      (IQR, 3.8-10.5) for women with late-onset PE. Compared with early-onset PE, the
      sFlt-1/PlGF ratio was significantly lower in controls (P < 0.001 at each
      timepoint) and in women with chronic hypertension (P < 0.001 at each timepoint),
      gestational hypertension (P < 0.001 at each timepoint) and late-onset PE (P <
      0.001 at each timepoint). A prediction model for early-onset PE was developed,
      which included the sFlt-1/PlGF ratio plus mean arterial pressure, being parous
      and previous PE, with areas under the receiver-operating characteristics curves
      of 0.86 (95% CI, 0.77-0.95), 0.91 (95% CI, 0.85-0.97) and 0.93 (95% CI, 0.86
      0.99) at 20, 24 and 28 weeks, respectively, and was superior to models using the
      sFlt-1/PlGF ratio alone or uterine artery mean pulsatility index. CONCLUSIONS:
      The sFlt-1/PlGF ratio can improve prediction of early-onset PE for women at risk
      of this condition. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 27883246
TI  - Intraoperative ultrasound-guided laparoscopic ovarian-tissue-preserving surgery
      for recurrent borderline ovarian tumor.

PMID- 27883247
TI  - 2-Methoxyestradiol-Mediated Induction of Frzb Contributes to Cell Death and
      Autophagy in MG63 Osteosarcoma Cells.
AB  - Osteosarcoma is a bone tumor that mainly affects children and adolescents.
      Although its pathogenesis is still not fully understood, activation of Wnt
      signaling has been implicated in the development and metastasis of osteosarcoma.
      In this report, we have investigated the effect of the anti-tumor compound, 2
      methoxyestradiol (2-ME) on Wnt antagonist frizzled-related protein b (Frzb), also
      known as secreted frizzled-related protein (sFRP)3 in human osteosarcoma (MG63)
      cells. Our results show that 2-ME treatment induces Frzb gene promoter activity,
      and increases Frzb mRNA and protein levels in osteosarcoma cells. In addition, 2
      ME treatment regulates downstream Wnt signaling, increasing the cytoplasmic
      levels of beta-catenin, and blocking beta-catenin-mediated Wnt activation in
      osteosarcoma cells. 2-ME-mediated induction of Frzb protein expression is
      specific to osteosarcoma cells, as it does not affect Frzb expression in normal
      primary human osteoblasts. Furthermore, 2-ME-induced apoptosis and autophagy are
      blocked in osteosarcoma cells transfected with Frzb siRNAs. Taken together, these
      studies demonstrate that Frzb protein plays an important role in 2-ME-mediated
      anti-tumor mechanisms in osteosarcoma cells. J. Cell. Biochem. 118: 1497-1504,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883248
TI  - Pyogranulomatous Pancarditis with Intramyocardial Bartonella henselae San Antonio
      2 (BhSA2) in a Dog.

PMID- 27883249
TI  - N-acetyl transferase 2/environmental factors and their association as a
      modulating risk factor for sporadic colon and rectal cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate the association between
      environmental factors and colon or rectal cancer after adjusting for N-acetyl
      transferase 2 (NAT2) phenotypes. METHODS: Ninety-six patients with sporadic colon
      cancer, 54 with sporadic rectal cancer and 162 control subjects were genotyped
      for NAT2-T341C, G590A, G857A, A845C, and C481T using sequencing and PCR-RFLP
      analysis. RESULTS: The risk for colon cancer was increased in carriers of the
      homozygous negative genotypes for NAT2*5C-T341C, NAT2*6B-G590A, NAT2*7B-G857A,
      NAT2*18-A845C, and NAT2*5A-C481T. The risk for rectal cancer was increased in
      carriers of the homozygous negative genotypes for NAT2*5C-T341C, NAT2*7B-G857A,
      and NAT2*5A-C481T. High fried red meat intake associated with NAT2-T341C, G590A,
      G857A, A845C, and C481T rapid acetylator allele determines a risk of 2.39
      (P=.002), 2.39 (P=.002), 2.37 (P=.002), 2.28 (P=.004), and 2.51 (P=.001),
      respectively, for colon cancer, whereas in the case of rectal cancer, the risk
      increased to 7.55 (P<.001), 7.7 (P<.001), 7.83 (P<.001), 7.51 (P<.001), and 8.62
      (P<.001), respectively. Alcohol consumption associated with the NAT2 -T341C,
      G590A, G857A, A845C, and C481T rapid acetylator allele induces a risk of 10.63
      (P<.001), 12.04 (P<.001), 9.76 (P<.001), 10.25 (P<.001), and 9.54 (P<.001),
      respectively, for colon cancer, whereas the risk for rectal cancer is 9.72
      (P<.001), 11.24 (P<.001), 13.07 (P<.001), 10.04 (P<.001), and 9.43 (P<.001),
      respectively. Smokers with NAT2-T341C, G590A, G857A, A845C, and C481T rapid
      acetylator allele have a risk of 4.87, 4.25, 4.18, 3.81, and 3.82, respectively,
      to develop colon cancer. CONCLUSIONS: Fried red meat, alcohol, and smoking
      increase the risk of sporadic CRC, especially of colon cancer, in the case of
      rapid acetylators for the NAT2 variants.

PMID- 27883251
TI  - MiR-892a Promotes Hepatocellular Carcinoma Cells Proliferation and Invasion
      Through Targeting CD226.
AB  - Our study is aim to investigate the influence of miR-892a on proliferative and
      invasive activities of human hepatocellular carcinoma (HCC) cells through
      regulating CD226 expression. QRT-PCR was used to detect the expression levels of
      miR-892a and CD226 mRNA in HCC tissues and adjacent tissues or HCC cells and
      normal cells whereas Western Blot was used to detect the CD226 protein expression
      in tissue and cell samples. Then HuH-7 cell line was selected for following
      assays and respectively transfected with miR-892a mimics, miR-NC, Plenti-GIII-Ubc
      CD226, and Plenti-GIII-Ubc followed by qRT-PCR assay to detect the miR-892a and
      CD226 expression. The luciferase reporter assay was conducted to determine if miR
      892a directly targeted CD226 and then CCK-8 assay, wound healing assay, Transwell
      assay, and flow cytometry were used to detect cell proliferation, migration,
      invasion ability, cell cycle, and cell apoptosis. What's more, relationships
      between expression levels of miR-892a or CD226 and overall survival (OS) or
      disease-free survival (DFS) of HCC patients were investigated based on TCGA
      database. MiR-892a was high-expressed in HCC tissues or cells while CD226 was low
      expressed. MiR-892a directly targeted CD226 and up-regulating miR-892a expression
      could promote proliferative, migrating, and invasive activities of HCC cells.
      Different expression levels of miR-892a and CD226 both related to the prognosis
      of HCC. MiR-892a promotes hepatocellular carcinoma cells proliferation and
      invasion through regulating CD226 expression. J. Cell. Biochem. 118: 1489-1496,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883252
TI  - Genetic differentiation and adaptive evolution at reproductive loci in incipient
      Drosophila species.
AB  - Accessory gland proteins (Acps) are part of the seminal fluid of male Drosophila
      flies. Some Acps have exceptionally high evolutionary rates and evolve under
      positive selection. Proper interactions between Acps and female reproductive
      molecules are essential for fertilization. These observations lead to suggestions
      that fast evolving Acps could be involved in speciation by promoting reproductive
      incompatibilities between emerging species. To test this hypothesis, we used
      population genetics data for three sibling species: D. mayaguana, D. parisiena
      and D. straubae. The latter two species are morphologically very similar and show
      only incipient reproductive isolation. This system allowed us to examine Acp
      evolution at different time frames with respect to speciation and reproductive
      isolation. Comparing data of 14 Acp loci with data obtained for other genomic
      regions, we found that some Acps show extraordinarily high levels of divergence
      between D. mayaguana and its two sister species D. parisiena and D. straubae.
      This divergence was likely driven by adaptive evolution at several loci. No fixed
      nucleotide differences were found between D. parisiena and D. straubae, however.
      Nevertheless, some Acp loci did show significant differentiation between these
      species associated with signs of positive selection; these loci may be involved
      in this early phase of the speciation process.

PMID- 27883250
TI  - 3D tract-specific local and global analysis of white matter integrity in
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by
      progressive decline in memory and other aspects of cognitive function. Diffusion
      weighted imaging (DWI) offers a non-invasive approach to delineate the effects of
      AD on white matter (WM) integrity. Previous studies calculated either some
      summary statistics over regions of interest (ROI analysis) or some statistics
      along mean skeleton lines (Tract Based Spatial Statistic [TBSS]), so they cannot
      quantify subtle local WM alterations along major tracts. Here, a comprehensive WM
      analysis framework to map disease effects on 3D tracts both locally and globally,
      based on a study of 200 subjects: 49 healthy elderly normal controls, 110 with
      mild cognitive impairment, and 41 AD patients has been presented. 18 major WM
      tracts were extracted with our automated clustering algorithm-autoMATE (automated
      Multi-Atlas Tract Extraction); we then extracted multiple DWI-derived parameters
      of WM integrity along the WM tracts across all subjects. A novel statistical
      functional analysis method-FADTTS (Functional Analysis for Diffusion Tensor Tract
      Statistics) was applied to quantify degenerative patterns along WM tracts across
      different stages of AD. Gradually increasing WM alterations were found in all
      tracts in successive stages of AD. Among all 18 WM tracts, the fornix was most
      adversely affected. Among all the parameters, mean diffusivity (MD) was the most
      sensitive to WM alterations in AD. This study provides a systematic workflow to
      examine WM integrity across automatically computed 3D tracts in AD and may be
      useful in studying other neurological and psychiatric disorders. Hum Brain Mapp
      38:1191-1207, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883253
TI  - The colostomy impact score: development and validation of a patient reported
      outcome measure for rectal cancer patients with a permanent colostomy. A
      population-based study.
AB  - AIM: The aim was to develop and validate a simple scoring system evaluating the
      impact of colostomy dysfunction on quality of life (QOL) in patients with a
      permanent stoma after rectal cancer treatment. METHOD: In this population-based
      study, 610 patients with a permanent colostomy after previous rectal cancer
      treatment during the period 2001-2007 completed two questionnaires: (i) the basic
      stoma questionnaire consisting of 22 items about stoma function with one anchor
      question addressing the overall stoma impact on QOL and (ii) the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      (EORTC QLQ) C30. Answers from half of the cohort were used to develop the score
      and subsequently validated on the remaining half. Logistic regression analyses
      identified and selected items for the score and multivariate analysis established
      the score value allocated to each item. RESULTS: The colostomy impact score
      includes seven items with a total range from 0 to 38 points. A score of >= 10
      indicates major colostomy impact (Major CI). The score has a sensitivity of 85.7%
      for detecting patients with significant stoma impact on QOL. Using the EORTC QLQ
      scales, patients with Major CI experienced significant impairment in their QOL
      compared to the Minor CI group. CONCLUSION: This new scoring system appears valid
      for the assessment of the impact on QOL from having a permanent colostomy in a
      Danish rectal cancer population. It requires validation in non-Danish populations
      prior to its acceptance as a valuable patient-reported outcome measure for
      patients internationally.

PMID- 27883254
TI  - The degree of extramural spread of T3 rectal cancer: an appeal to the American
      Joint Committee on Cancer.
AB  - The T3 category of the TNM classification includes over 60% of all rectal tumours
      and encompasses the greatest variance in cancer-specific end-points than any
      other T category. The most recent edition of the cancer staging handbook of the
      American Joint Committee on Cancer (AJCC) dated 2010 does not divide T3 tumours
      into subgroups which reflect cancer-specific outcome more sensitively. The
      original aim of the present study was to review the literature to assess the
      influence of the degree of extramural extent of T3 rectal cancer on local
      recurrence and survival. An article written by the authors was accepted for
      publication but was withdrawn immediately after they became aware of the
      publication of the 4th edition of the TNM Supplement by the Union for
      International Cancer Control dated 2012, which was not accessible by the search
      system used. This article dealt with the subdivision of the T3 category although
      this was not included in the most up-to-date AJCC guidelines and was stated to be
      'entirely optional'. Medline, PubMed and Cochrane Library searches were performed
      to identify all studies that investigated the degree of extramural spread and its
      relationship to survival and local recurrence. Twenty-two studies were identified
      of which 12 assessed the degree of histopathological extramural spread measured
      in millimetres. In 18 of the 22 studies the degree of extramural spread was a
      statistically significant prognostic factor for survival and local recurrence.
      Analysis of the studies indicated that the subdivision of category T3 rectal
      cancer into two subgroups of extramural spread <= 5 mm or more than 5 mm resulted
      in markedly different survival and local recurrence rates. The data were
      insufficient to allow validation of any greater subdivision. Measurement of the
      extent of extramural spread by MRI before any treatment agreed with the
      histopathological measurement in the surgical specimen to within 1 mm. The extent
      of extramural spread in T3 rectal cancer measured in millimetres is a powerful
      prognostic factor. A subdivision of T3 into T3a and T3b of less than or equal to
      or more than 5 mm appears to give the greatest discrimination of local recurrence
      and survival. Preoperative T3 subdivision by MRI has the same sensitivity as
      histopathological examination of the resected specimen. Given the clinical need
      for the pretreatment classification of the T3 category for oncological management
      planning, the evidence strongly indicates that the subdivision of the T3 category
      by MRI should be formally considered as part of the TNM staging system for rectal
      cancer.

PMID- 27883256
TI  - Detecting AGG Interruptions in Male and Female FMR1 Premutation Carriers by
      Single-Molecule Sequencing.
AB  - The FMR1 gene contains an unstable CGG repeat in its 5' untranslated region.
      Premutation alleles range between 55 and 200 repeat units and confer a risk for
      developing fragile X-associated tremor/ataxia syndrome or fragile X-associated
      primary ovarian insufficiency. Furthermore, the premutation allele often expands
      to a full mutation during female germline transmission giving rise to the fragile
      X syndrome. The risk for a premutation to expand depends mainly on the number of
      CGG units and the presence of AGG interruptions in the CGG repeat. Unfortunately,
      the detection of AGG interruptions is hampered by technical difficulties. Here,
      we demonstrate that single-molecule sequencing enables the determination of not
      only the repeat size, but also the complete repeat sequence including AGG
      interruptions in male and female alleles with repeats ranging from 45 to 100 CGG
      units. We envision this method will facilitate research and diagnostic analysis
      of the FMR1 repeat expansion.

PMID- 27883255
TI  - Genome-wide association of functional traits linked with Campylobacter jejuni
      survival from farm to fork.
AB  - Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide,
      primarily associated with the consumption of contaminated poultry. C. jejuni
      lineages vary in host range and prevalence in human infection, suggesting
      differences in survival throughout the poultry processing chain. From 7343 MLST
      characterised isolates, we sequenced 600 C. jejuni and C. coli isolates from
      various stages of poultry processing and clinical cases. A genome-wide
      association study (GWAS) in C. jejuni ST-21 and ST-45 complexes identified
      genetic elements over-represented in clinical isolates that increased in
      frequency throughout the poultry processing chain. Disease-associated SNPs were
      distinct in these complexes, sometimes organised in haplotype blocks. The
      function of genes containing associated elements was investigated, demonstrating
      roles for cj1377c in formate metabolism, nuoK in aerobic survival and oxidative
      respiration, and cj1368-70 in nucleotide salvage. This work demonstrates the
      utility of GWAS for investigating transmission in natural zoonotic pathogen
      populations and provides evidence that major C. jejuni lineages have distinct
      genotypes associated with survival, within the host specific niche, from farm to
      fork.

PMID- 27883258
TI  - Bivalent Display of Dicysteine on Peptide Nucleic Acids for Homogenous DNA/RNA
      Detection through in Situ Fluorescence Labelling.
AB  - Fluorogenic probes that signal the presence of specific DNA or RNA sequences are
      key enabling tools for molecular disease diagnosis and imaging studies. Usually,
      at least one fluorophore is attached through covalent bonding to an
      oligonucleotide probe. However, the additional conjugation step increases costs.
      Here we introduce a method that avoids the requirement for the preparation of
      fluorescence-labelled oligonucleotides and provides the opportunity to alter the
      fluorogenic reporter dye without resynthesis. The method is based on adjacent
      hybridization of two dicysteine-containing peptide nucleic acid (PNA) probes to
      form a bipartite tetracysteine motif that binds profluorescent bisarsenical dyes
      such as FIAsH, ReAsH or CrAsH. Binding is accompanied by strong increases in
      fluorescence emission (with response factors of up to 80-fold and high brightness
      up to 50 mL mol-1  cm-1 ). The detection system provides sub-nanomolar limits of
      detection and allows discrimination of single nucleotide variations through more
      than 20-fold changes in fluorescence intensity. To demonstrate its usefulness,
      the FIAsH-based readout of the bivalent CysCys-PNA display was interfaced with a
      rolling-circle amplification (RCA) assay used to detect disease-associated
      microRNA let-7a.

PMID- 27883257
TI  - Determining the binding affinities of prostate-specific antigen to lectins: SPR
      and microarray approaches.
AB  - Prostate cancer (PCa) is one of the most common newly diagnosed cancers among men
      and we focused on its traditional biomarker, prostate-specific antigen (PSA),
      using targeted glycomics-based strategies. The aberrant glycosylation pattern of
      PSA may serve as a valuable tool for improving PCa diagnosis including its early
      stage. In this study, we evaluated the usability of two techniques, surface
      plasmon resonance and protein microarray assay, for the study and
      characterization of interactions of PSA (both free and complexed) with six
      lectins (SNA, ConA, RCA, AAL, WGA and MAA II). The information on the character
      of such interactions is important for the application of lectins as prospective
      bioreceptors for biomarker glycoprofiling in a follow-up biosensing assays. SPR
      as well as established bioanalytical techniques allowed determination of KD
      values of PSA-lectin interactions in a more reliable way than protein microarray.
      The protein microarray method did not allow accurate quantification of KD values.
      However, the features of a microarray approach, such as speed and costs, enabled
      the screening and estimation of the nature of lectin-glycan biomarker interaction
      in an effective and time-saving way. All of the tested lectins interacted with
      commercial PSA standard isolated from healthy persons, except MAA II which
      reacted only very weakly.

PMID- 27883259
TI  - The association between intensified medical treatment, time to surgery and
      ileocolic specimen length in Crohn's disease.
AB  - AIM: During the last decade, treatment protocols have changed for patients with
      ileocolic Crohn's disease. Anti-tumour necrosis factor (anti-TNF) has become part
      of standard medical treatment, usually in a step-up approach. The aim was to
      analyse if improved medical treatment has resulted in more limited ileocolic
      resections and a longer interval between diagnosis and surgery. METHOD: Patients
      undergoing ileocolic resection for Crohn's disease were included (1999-2014).
      Patient characteristics were compared to the results of a population-based study
      (between 2004 and 2010) previously performed in the catchment area of the present
      tertiary referral centre. Time trends were analysed using the Cochrane-Armitage
      trend, Spearman's correlation coefficient and linear regression. RESULTS: In
      total, 195 patients undergoing ileocolic resection were included. Patient
      characteristics were not significantly different from the background cohort,
      confirming a representative study group. Sixty-three patients were men (32.3%,
      median age at surgery 30.0 years, interquartile range 23.0-40.0). Anti-TNF and
      immunomodulator use prior to surgery increased significantly during the study
      period (chi2  = 49.1, P < 0.001). Over the years, a significant increase in time
      from diagnosis to operation was found (median 39.0 months, interquartile range
      12.0-86.0, rho 0.175, P = 0.014). The length of the resected ileum did not change
      significantly (median 20.0 cm, interquartile range 12.0-30.0, rho -0.107, P =
      0.143). The number of fistulas or postoperative complications that needed re
      intervention was not significantly different between the groups with or without
      anti-TNF. CONCLUSION: This study demonstrated that over time patients with
      ileocolic Crohn's disease who eventually underwent ileocolic resection have been
      treated more intensively medically; however, this did not result in reduced
      specimen size.

PMID- 27883260
TI  - Use of incretin agents and risk of acute and chronic pancreatitis: A population
      based cohort study.
AB  - AIM: To determine the association between the use of incretin agents (dipeptidyl
      peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) for the
      treatment of type 2 diabetes mellitus (T2DM) and the risk of any, acute and
      chronic pancreatitis. RESEARCH DESIGN AND METHODS: A population-based cohort
      study was conducted using data from the UK Clinical Practice Research Datalink
      (CPRD 2007-2012). A total of 182 428 adult patients with >=1 non-insulin
      antidiabetic drug (NIAD) prescription were matched to control subjects without
      diabetes. Cox regression was used to estimate adjusted hazard ratios (HRs) and
      95% confidence intervals (CIs) of pancreatitis in incretin-users (N = 28 370)
      compared with controls and with other NIAD users. Adjustments were made for
      lifestyle, disease and drug history. In a sensitivity analysis, a new-user design
      was used. RESULTS: Current incretin users had a 1.5-fold increased risk of any
      pancreatitis compared with NIAD users (adjusted HR 1.47, 95% CI 1.06-2.04). In
      incident current incretin users the risk of any and acute pancreatitis was
      increased 2.1- and 2.0-fold compared with NIAD users (adjusted HR 2.12, 95% CI
      1.31-3.43 and adjusted HR 1.96, 95% CI 1.13-3.41), whereas there was no increased
      risk found for chronic pancreatitis. CONCLUSIONS: Incretin use was associated
      with an increased risk of any pancreatitis. Moreover, risk of any and acute
      pancreatitis was higher when applying a new-user design. We were not able to
      detect an association with chronic pancreatitis, but the number in this subgroup
      was small.

PMID- 27883261
TI  - Prevention of neural tube defects in Lrp2 mutant mouse embryos by folic acid
      supplementation.
AB  - BACKGROUND: Neural tube defects (NTDs) are among the most common structural birth
      defects in humans and are caused by the complex interaction of genetic and
      environmental factors. Periconceptional supplementation with folic acid can
      prevent NTDs in both mouse models and human populations. A better understanding
      of how genes and environmental factors interact is critical toward development of
      rational strategies to prevent NTDs. Low density lipoprotein-related protein 2
      (Lrp2) is involved in endocytosis of the folic acid receptor among numerous other
      nutrients and ligands. METHODS: We determined the effect of iron and/or folic
      acid supplementation on the penetrance of NTDs in the Lrp2null mouse model. The
      effects of supplementation on folate and iron status were measured in embryos and
      dams. RESULTS: Periconceptional dietary supplementation with folic acid did not
      prevent NTDs in Lrp2 mutant embryos, whereas high levels of folic acid
      supplementation by intraperitoneal injection reduced incidence of NTDs.
      Importantly, Lrp2null/+ dams had reduced blood folate levels that improved with
      daily intraperitoneal injections of folate but not dietary supplementation. On
      the contrary, iron supplementation had no effect on the penetrance of NTDs in
      Lrp2 mutant embryos and negated the preventative effect of folic acid
      supplementation in Lrp2null/null mutants. CONCLUSION: Lrp2 is required for folate
      homeostasis in heterozygous dams and high levels of supplementation prevents
      NTDs. Furthermore, high levels of dietary iron supplementation interfered with
      folic acid supplementation negating the positive effects of supplementation in
      this model. Birth Defects Research 109:16-26, 2017. (c) 2016 The Authors Birth
      Defects Published by Wiley Periodicals, Inc.

PMID- 27883262
TI  - Phytochemicals enhance antioxidant enzyme expression to protect against NSAID
      induced oxidative damage of the gastrointestinal mucosa.
AB  - The gastrointestinal (GI) mucosa provides the first protective barrier for
      digested food and xenobiotics, which are easily attacked by toxic substances.
      Nonsteroidal anti-inflammatory drugs, including aspirin, diclofenac,
      indomethacin, and ketoprofen, are widely used in clinical medicine, but these
      drugs may cause oxidative stress, leading to GI damage such as ulcers.
      Lansoprazol, omeprazole, and other clinical drugs are widely used to treat
      duodenal and gastric ulcers and have been shown to have multiple biological
      functions, such as antioxidant activity and the ability to upregulate antioxidant
      enzymes in vivo. Therefore, the reduction of oxidative stress may be an effective
      curative strategy for preventing and treating nonsteroidal anti-inflammatory drug
      induced ulcers of the GI mucosa. Phytochemicals, such as dietary phenolic
      compounds, phenolic acids, flavan-3-ols, flavonols, flavonoids, gingerols,
      carotenes, and organosulfur, are common antioxidants in fruits, vegetables, and
      beverages. A large amount of evidence has demonstrated that natural
      phytochemicals possess bioactivity and potential health benefits, such as
      antioxidant, anti-inflammatory, and antibacterial benefits, and they can prevent
      digestive disease processes. In this review, we summarize the literature on
      phytochemicals with biological effects, such as angiogenic, antioxidant,
      antiapoptotic, anti-inflammatory, and antiulceration effects, and their related
      mechanisms are also discussed.

PMID- 27883263
TI  - Cargo selectivity of yeast sorting nexins.
AB  - Sorting nexins are PX domain-containing proteins that bind phospholipids and
      often act in membrane trafficking where they help to select cargo. However, the
      functions and cargo specificities of many sorting nexins are unknown. Here, a
      high-throughput imaging screen was used to identify new sorting nexin cargo in
      the yeast Saccharomyces cerevisiae. Deletions of 9 different sorting nexins were
      screened for mislocalization of a set of green fluorescent protein (GFP)-tagged
      membrane proteins found at the plasma membrane, Golgi or endosomes. This
      identified 27 proteins that require 1 or more sorting nexins for their correct
      localization, 23 of which represent novel sorting nexin cargo. Nine hits whose
      sorting was dependent on Snx4, the sorting nexin-containing retromer complex, or
      both retromer and Snx3, were examined in detail to search for potential sorting
      motifs. We identified cytosolic domains of Ear1, Ymd8 and Ymr010w that conferred
      retromer-dependent sorting on a chimeric reporter and identified conserved
      residues required for this sorting in a functional assay. This work defined a
      consensus sequence for retromer and Snx3-dependent sorting.

PMID- 27883264
TI  - Mucosa-associated biohydrogenating microbes protect the simulated colon
      microbiome from stress associated with high concentrations of poly-unsaturated
      fat.
AB  - Polyunsaturated fatty acids (PUFAs) may affect colon microbiome homeostasis by
      exerting (specific) antimicrobial effects and/or interfering with mucosal biofilm
      formation at the gut mucosal interface. We used standardized batch incubations
      and the Mucosal-Simulator of the Human Microbial Intestinal Ecosystem (M-SHIME)
      to show the in vitro luminal and mucosal effects of the main PUFA in the Western
      diet, linoleic acid (LA). High concentrations of LA were found to decrease
      butyrate production and Faecalibacterium prausnitzii numbers dependent on LA
      biohydrogenation to vaccenic acid (VA) and stearic acid (SA). In faecal batch
      incubations, LA biohydrogenation and butyrate production were positively
      correlated and SA did not inhibit butyrate production. In the M-SHIME, addition
      of a mucosal environment stimulated biohydrogenation to SA and protected F.
      prausnitzii from inhibition by LA. This was probably due to the preference of two
      biohydrogenating genera Roseburia and Pseudobutyrivibrio for the mucosal niche.
      Co-culture batch incubations using Roseburia hominis and F. prausnitzii validated
      these observations. Correlations networks further uncovered the central role of
      Roseburia and Pseudobutyrivibrio in protecting luminal and mucosal SHIME
      microbiota from LA-induced stress. Our results confirm how cross-shielding
      interactions provide resilience to the microbiome and demonstrate the importance
      of biohydrogenating, mucosal bacteria for recovery from LA stress.

PMID- 27883266
TI  - Silencing of ecdysone receptor, insect intestinal mucin and sericotropin genes by
      bacterially produced double-stranded RNA affects larval growth and development in
      Plutella xylostella and Helicoverpa armigera.
AB  - RNA interference mediated gene silencing, which is triggered by double-stranded
      RNA (dsRNA), has become a important tool for functional genomics studies in
      various systems, including insects. Bacterially produced dsRNA employs the use of
      a bacterial strain lacking in RNaseIII activity and harbouring a vector with dual
      T7 promoter sites, which allow the production of intact dsRNA molecules. Here, we
      report an assessment of the functional relevance of the ecdysone receptor, insect
      intestinal mucin and sericotropin genes through silencing by dsRNA in two
      lepidopteran insect pests, Helicoverpa armigera and Plutella xylostella, both of
      which cause serious crop losses. Oral feeding of dsRNA led to significant
      reduction in transcripts of the target insect genes, which caused significant
      larval mortality with various moulting anomalies and an overall developmental
      delay. We also found a significant decrease in reproductive potential in female
      moths, with a drop in egg laying and compromised egg hatching from treated larvae
      as compared to controls. dsRNA was stable in the insect gut and was efficiently
      processed into small interfering RNAs (siRNAs), thus accounting for the
      phenotypes observed in the present work. The study revealed the importance of
      these genes in core insect processes, which are essential for insect development
      and survival.

PMID- 27883267
TI  - Translocation of Tektin 3 to the equatorial segment of heads in bull spermatozoa
      exposed to dibutyryl cAMP and calyculin A.
AB  - Tektins (TEKTs) are filamentous proteins associated with microtubules in cilia,
      flagella, basal bodies, and centrioles. Five TEKTs (TEKT1, -2, -3, -4, and -5)
      have been identified as components of mammalian sperm flagella. We previously
      reported that TKET1 and -3 are also present in the heads of rodent spermatozoa.
      The present study clearly demonstrates that TEKT2 is present at the acrosome cap
      whereas TEKT3 resides just beneath the plasma membrane of the post-acrosomal
      region of sperm heads in unactivated bull spermatozoa, and builds on the
      distributional differences of TEKT1, -2, and -3 on sperm heads. We also
      discovered that hyperactivation of bull spermatozoa by cell-permeable cAMP and
      calyculin A, a protein phosphatase inhibitor, promoted translocation of TEKT3
      from the post-acrosomal region to the equatorial segment in sperm heads, and that
      TEKT3 accumulated at the equatorial segment is lost upon acrosome reaction. Thus,
      translocation of TEKT3 to the equatorial segment may be a capacitation- or
      hyperactivation-associated phenomenon in bull spermatozoa. Mol. Reprod. Dev. 84:
      30-43, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27883265
TI  - Genomic approaches to the assessment of human spina bifida risk.
AB  - Structural birth defects are a leading cause of mortality and morbidity in
      children world-wide, affecting as much as 6% of all live births. Among these
      conditions, neural tube defects (NTDs), including spina bifida and anencephaly,
      arise from a combination of complex gene and environment interactions that are as
      yet poorly understood within human populations. Rapid advances in massively
      parallel DNA sequencing and bioinformatics allow for analyses of the entire
      genome beyond the 2% of the genomic sequence covering protein coding regions.
      Efforts to collect and analyze these large datasets hold promise for illuminating
      gene network variations and eventually epigenetic events that increase individual
      risk for failure to close the neural tube. In this review, we discuss current
      challenges for DNA genome sequence analysis of NTD affected populations, and
      compare experience in the field with other complex genetic disorders for which
      large datasets are accumulating. The ultimate goal of this research is to find
      strategies for optimizing conditions that promote healthy birth outcomes for
      individual couples. Birth Defects Research 109:120-128, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27883270
TI  - Pharmacovigilance Skills, Knowledge and Attitudes in our Future Doctors - A
      Nationwide Study in the Netherlands.
AB  - Pharmacovigilance centres monitor the safety of drugs, based on adverse drug
      reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies.
      However, the under-reporting of ADRs remains a major problem. Our aim was to
      investigate preparedness of future doctors for their role in pharmacovigilance,
      by assessing their pharmacovigilance awareness, skills and knowledge. The study
      was a nationwide e-survey among medical students (third to sixth year) of all
      eight medical schools in the Netherlands. The survey consisted of questions
      regarding pharmacovigilance awareness, skills and knowledge. Overall, 874
      students provided informed consent and participated (response 12%). Almost all
      students (96%) intended to report serious ADRs in their future practice. Almost
      half (44%) of the students did not know where to report an ADR, and 78% did not
      know which items were necessary for a good-quality ADR report. While more than
      78% of the students agreed that pharmacovigilance is an important topic in their
      medical education, only 26% found that their current curriculum covered
      pharmacovigilance adequately. Although ADR reporting is considered relevant and
      important among future doctors, many do not know where and what to report. This
      is highly undesirable and should have consequences for pharmacotherapy teaching.

PMID- 27883271
TI  - High-throughput downstream process development for cell-based products using
      aqueous two-phase systems (ATPS) - A case study.
AB  - The availability of preparative-scale downstream processing strategies for cell
      based products presents a critical juncture between fundamental research and
      clinical development. Aqueous two-phase systems (ATPS) present a gentle,
      scalable, label-free, and cost-effective method for cell purification, and are
      thus a promising tool for downstream processing of cell-based therapeutics. Here,
      the application of a previously developed robotic screening platform that enables
      high-throughput cell partitioning analysis in ATPS is reported. In the present
      case study a purification strategy for two model cell lines based on high
      throughput screening (HTS)-data and countercurrent distribution (CCD)-modeling,
      and validated the CCD-model experimentally is designed. The obtained data are
      shown an excellent congruence between CCD-model and experimental data, indicating
      that CCD-models in combination with HTS-data are a powerful tool in downstream
      process development. Finally, the authors are shown that while cell cycle phase
      significantly influences cell partitioning, cell type specific differences in
      surface properties are the main driving force in charge-dependent separation of
      HL-60 and L929 cells. In order to design a highly robust purification process it
      is, however, advisable to maintain constant growth conditions.

PMID- 27883269
TI  - Oil-Fortified Maize Porridge Increases Absorption of Lumefantrine in Children
      with Uncomplicated Falciparum Malaria.
AB  - Artemether-lumefantrine (AL) is a first-line treatment for uncomplicated malaria.
      Absorption of lumefantrine (LUM) is fat dependent, and in children, intake is
      recommended with milk. We investigated whether oil-fortified maize porridge can
      be an alternative when milk is not available. In an open-label pharmacokinetic
      study, Ugandan children <5 years with uncomplicated Plasmodium falciparum malaria
      were randomized to receive standard six-dose AL treatment [one tablet (20 mgA/120
      mg LUM) if <15 kg and two tablets if >15 kg] with milk (A) or maize porridge plus
      oil (B). Parametric two-sample t-test was used to compare relative oral LUM
      bioavailability. The primary end-point was LUM exposure till 8 hr after the first
      dose (AUC0-8 hr ). Secondary outcome included day 7 concentrations (d7LUM ), LUM
      exposure between days 7 and 28 (AUCd7-28 ) and day 28 PCR-adjusted
      parasitological response. Evaluable children (n = 33) included 16 in arm A and 17
      in arm B. The AUC0-8 hr was comparable between A and B [geometric mean (95% CI):
      6.01 (3.26-11.1) versus 6.26 (4.5-8.43) hr*MUg/mL, p = 0.9]. Less interindividual
      variability in AUC0-8 hr was observed in B (p = 0.01), but d7LUM and AUCd7-28
      were comparable. Children receiving two tablets had significantly higher exposure
      than those receiving one tablet [median d7LUM (505 versus 289 ng/mL, p = 0.02)
      and AUCd7-28 (108 versus 41 hr*MUg/mL, p = 0.006)]. One parasitological failure
      (d28 recrudescence) was observed. Our findings suggest that oil-fortified maize
      porridge can be an alternative to milk in augmenting absorption of LUM. The lower
      LUM exposure observed in children dosed with one AL tablet needs further
      attention.

PMID- 27883268
TI  - Formation and carbon monoxide-dependent dissociation of Allochromatium vinosum
      cytochrome c' oligomers using domain-swapped dimers.
AB  - The number of artificial protein supramolecules has been increasing; however,
      control of protein oligomer formation remains challenging. Cytochrome c' from
      Allochromatium vinosum (AVCP) is a homodimeric protein in its native form, where
      its protomer exhibits a four-helix bundle structure containing a covalently bound
      five-coordinate heme as a gas binding site. AVCP exhibits a unique reversible
      dimer-monomer transition according to the absence and presence of CO. Herein,
      domain-swapped dimeric AVCP was constructed and utilized to form a tetramer and
      high-order oligomers. The X-ray crystal structure of oxidized tetrameric AVCP
      consisted of two monomer subunits and one domain-swapped dimer subunit, which
      exchanged the region containing helices alphaA and alphaB between protomers. The
      active site structures of the domain-swapped dimer subunit and monomer subunits
      in the tetramer were similar to those of the monomer subunits in the native
      dimer. The subunit-subunit interactions at the interfaces of the domain-swapped
      dimer and monomer subunits in the tetramer were also similar to the subunit
      subunit interaction in the native dimer. Reduced tetrameric AVCP dissociated to a
      domain-swapped dimer and two monomers upon CO binding. Without monomers, the
      domain-swapped dimers formed tetramers, hexamers, and higher-order oligomers in
      the absence of CO, whereas the oligomers dissociated to domain-swapped dimers in
      the presence of CO, demonstrating that the domain-swapped dimer maintains the CO
      induced subunit dissociation behavior of native ACVP. These results suggest that
      protein oligomer formation may be controlled by utilizing domain swapping for a
      dimer-monomer transition protein.

PMID- 27883273
TI  - A velocity tracking approach for the data assimilation problem in blood flow
      simulations.
AB  - Several advances have been made in data assimilation techniques applied to blood
      flow modeling. Typically, idealized boundary conditions, only verified in
      straight parts of the vessel, are assumed. We present a general approach, on the
      basis of a Dirichlet boundary control problem, that may potentially be used in
      different parts of the arterial system. The relevance of this method appears when
      computational reconstructions of the 3D domains, prone to be considered
      sufficiently extended, are either not possible, or desirable, because of
      computational costs. On the basis of taking a fully unknown velocity profile as
      the control, the approach uses a discretize then optimize methodology to solve
      the control problem numerically. The methodology is applied to a realistic 3D
      geometry representing a brain aneurysm. The results show that this data
      assimilation approach may be preferable to a pressure control strategy and that
      it can significantly improve the accuracy associated to typical solutions
      obtained using idealized velocity profiles.

PMID- 27883272
TI  - Circulating adipocyte-derived exosomal MicroRNAs associated with decreased
      insulin resistance after gastric bypass.
AB  - OBJECTIVE: Exosomes from obese adipose contain dysregulated microRNAs linked to
      insulin signaling, as compared with lean controls, providing a direct connection
      between adiposity and insulin resistance. This study tested the hypotheses that
      gastric bypass surgery and its subsequent weight loss would normalize adipocyte
      derived exosomal microRNAs associated with insulin signaling and the associated
      metabolome related to glucose homeostasis. METHODS: African American female
      subjects with obesity (N = 6; age: 38.5 +/- 6.8 years; BMI: 51.2 +/- 8.8 kg/m2 )
      were tested before and 1 year after surgery. Insulin resistance (HOMA), serum
      metabolomics, and global microRNA profiles of circulating adipocyte-derived
      exosomes were evaluated via ANCOVA and correlational analyses. RESULTS: One year
      postsurgery, patients showed decreased BMI (-18.6 +/- 5.1 kg/m2 ; P < 0.001),
      ameliorated insulin resistance (HOMA: 1.94 +/- 0.6 presurgery, 0.49 +/- 0.1
      postsurgery; P < 0.001), and altered metabolites including branched chain amino
      acids (BCAA). Biological pathway analysis of predicted mRNA targets of 168
      surgery-responsive microRNAs (P < 0.05) identified the insulin signaling pathway
      (P = 1.27E-10; 52/138 elements), among others, in the data set. The insulin
      signaling pathway was also a target of 10 microRNAs correlated to changes in HOMA
      (P < 0.05; r > 0.4), and 48 microRNAs correlated to changes in BCAA levels.
      CONCLUSIONS: These data indicate that circulating adipocyte-derived exosomes are
      modified following gastric bypass surgery and correlate to improved postsurgery
      insulin resistance.

PMID- 27883274
TI  - Impact of the Chronic Omega-3 Fatty Acids Supplementation in Hemiparkinsonism
      Model Induced by 6-Hydroxydopamine in Rats.
AB  - Parkinson's disease (PD) is characterized by a progressive degeneration of
      dopaminergic neurons in the substantia nigra. The neuronal degeneration may
      result from the convergence of a number of different pathogenic factors,
      including apoptosis, excitotoxicity and oxidative stress. Many studies emphasize
      the importance of omega-3 polyunsaturated fatty acids (omega-3 PUFAs) in vital
      processes such as maintenance of the properties of cell membranes and the
      participation in signal transduction and biodynamic activity of neuronal
      membranes. In this study, the protective effect of omega-3 PUFA administration on
      the 6-hydroxydopamine (6-OHDA) model of PD in rats was investigated. omega-3 PUFA
      (1.5 and 3.0 g/kg) was orally administered by gavage during 28 consecutive days
      to male Wistar rats. On the 4th day, hemiparkinsonism was induced through
      intrastriatal injection of 6-OHDA. On the 25th day, the animals were submitted to
      behavioural analysis. On the 28th day, after euthanasia, the brain areas were
      collected for neurochemical evaluation. omega-3 PUFAs (1.5 and 3.0 g/kg) restored
      monoamine and amino acid levels on the striatum from hemiparkinsonian rats,
      followed by reduction in the number of apomorphine-induced rotations and
      promotion of a partial locomotor recovery. In addition, omega-3 PUFAs (1.5 and
      3.0 g/kg) decreased the lipid peroxidation levels and nitrite levels in the brain
      areas from hemiparkinsonian rats. Thus, this study suggests that supplementation
      with omega-3 PUFAs prevents behavioural and neurochemical disturbances induced by
      6-OHDA, presenting a potential neuroprotective action.

PMID- 27883275
TI  - Comparative analysis of three human adipocyte size measurement methods and their
      relevance for cardiometabolic risk.
AB  - OBJECTIVE: To determine whether adipocyte diameters from three measurement
      methods are similarly associated with adiposity measurements and cardiometabolic
      variables. METHODS: Surgical samples of omental and abdominal subcutaneous
      adipose tissue were obtained in a sample of 60 women (age 35-59 years; body mass
      index 20.3-41.1 kg/m2 ). Median adipocyte diameter of the main cell population
      was determined by collagenase digestion, osmium tetroxide fixation, and
      histological analysis. Adiposity and cardiometabolic risk factors were assessed.
      RESULTS: Adipocyte diameter was consistently smaller with formalin fixation than
      with collagenase digestion, whereas osmium-fixed cells were larger (P < 0.0001,
      for all). Median adipocyte diameters derived from all methods were
      intercorrelated (r = 0.46-0.83, P < 0.001 for all). Positive associations were
      found between adipocyte diameters from all techniques and regional or total
      adiposity measurements (P < 0.01 for all). Omental adipocyte diameter was
      positively associated with fasting glucose, insulin, and homeostatic model
      assessment of insulin resistance (r = 0.30-0.52, P < 0.05 for all), with osmium
      fixed cell size as a stronger correlate. Osmium-fixed cell diameter was also a
      better correlate of plasma adiponectin and leptin. CONCLUSIONS: Although
      measurement techniques generated systematic differences in adipocyte size,
      associations with adiposity were only slightly affected by the technique. Osmium
      fixation generated stronger associations with cardiometabolic risk factors than
      collagenase digestion and histological analysis.

PMID- 27883276
TI  - Microporous Organic Polymers Based on Hyper-Crosslinked Coal Tar: Preparation and
      Application for Gas Adsorption.
AB  - Hyper-crosslinked polymers (HCPs) are promising materials for gas capture and
      storage, but high cost and complicated preparation limit their practical
      application. In this paper, a new type of HCPs (CTHPs) was synthesized through a
      one-step mild Friedel-Crafts reaction with low-cost coal tar as the starting
      material. Chloroform was utilized as both solvent and crosslinker to generate a
      three-dimensional crosslinked network with abundant micropores. The maximum BET
      surface area of the prepared CTHPs could reach up to 929 m2  g-1 . Owing to the
      high affinity between the heteroatoms on the coal-tar building blocks and the CO2
      molecules, the adsorption capacity of CTHPs towards CO2 reached up to 14.2 wt %
      (1.0 bar, 273 K) with a high selectivity (CO2 /N2 =32.3). Furthermore, the
      obtained CTHPs could adsorb 1.27 wt % H2 at 1.0 bar and 77.3 K, and also showed
      capacity for the capture of high organic vapors at room temperature. In
      comparison with other reported porous organic polymers, CTHPs have the advantages
      of low-cost, easy preparation, and high gas-adsorption performance, making them
      suitable for mass production and practical use in the future.

PMID- 27883277
TI  - Application of THz Vibrational Spectroscopy to Molecular Characterization and the
      Theoretical Fundamentals: An Illustration Using Saccharide Molecules.
AB  - This work illustrates several theoretical fundamentals for the application of THz
      vibrational spectroscopy to molecular characterization in the solid state using
      two different types of saccharide systems as examples. Four subjects have been
      specifically addressed: (1) the qualitative differences in the molecular
      vibrational signatures monitored by THz and mid-IR vibrational spectroscopy; (2)
      the selection rules for THz vibrational spectroscopy as applied to crystalline
      and amorphous systems; (3) a normal mode simulation, using alpha-l-xylose as an
      example; and (4) a rigorous mode analysis to quantify the percentage
      contributions of the intermolecular and intramolecular vibrations to the normal
      mode of interest.

PMID- 27883278
TI  - A genetic link between prepregnancy body mass index, postpartum weight retention,
      and offspring weight in early childhood.
AB  - OBJECTIVE: The effects of maternal prepregnancy body mass index (BMI) and
      gestational weight gain (GWG) on maternal and offspring obesity traits, as well
      as the maternal and offspring genetic contribution to GWG and postpartum weight
      retention, were examined. METHODS: Blood samples from mothers (n = 608) and
      offspring (n = 541) were genotyped for 83 BMI-associated SNPs and 47 waist-to-hip
      ratio (WHR)-associated SNPs. Linear regression and mixed-effects regression
      models were performed to examine clinical epidemiological and genetic
      associations with unweighted and weighted BMI and WHR genetic risk scores (GRS).
      RESULTS: Prepregnancy BMI was positively associated with offspring weight and BMI
      Z-score from birth to 5 years. GWG was positively associated with maternal
      postpartum weight retention at 1 and 5 years and with offspring weight Z-score
      from birth to 5 years old. The maternal unweighted BMI GRS was associated with
      prepregnancy BMI, postpartum weight retention at 5 years, and offspring weight Z
      score from birth to 5 years old, but not associated with GWG. Both maternal and
      offspring unweighted WHR GRSs were negatively associated with GWG. CONCLUSIONS:
      Maternal BMI-associated SNPs may contribute to the genetic link between
      prepregnancy BMI variation, long-term postpartum weight retention, and offspring
      birth weight and longitudinal weight. Maternal and offspring WHR-associated SNPs
      may contribute to GWG variation.

PMID- 27883279
TI  - Fast Track to Molar-Mass Distributions of Technical Lignins.
AB  - Technical lignins (waste products obtained from wood pulping or biorefinery
      processes) have so far required lengthy analysis procedures and different eluents
      for molar-mass analysis by gel permeation chromatography (GPC). This challenge
      has become more pressing recently since attempts to utilize lignins have
      increased, leading to skyrocketing numbers of samples to be analyzed. A new
      approach, which uses the eluent DMSO/LiBr (0.5 % w/v) and converts lignosulfonate
      salts into their acidic form before analysis, overcomes these limitations by
      enabling measurement of all kinds of lignins (kraft, organosolv, soda,
      lignosulfonates) in the same size-exclusion chromatography (SEC) system without
      the necessity of prior time-consuming derivatization steps. In combination with
      ultra-performance liquid chromatography (UPLC), analysis times are shortened to
      one tenth of classical lignin GPC. The new approach is presented, along with a
      comparison of GPC and UPLC methods and a critical discussion of the analytical
      parameters.

PMID- 27883280
TI  - Phase I study of irinotecan for previously treated lung cancer patients with the
      UGT1A1*28 or *6 polymorphism: Results of the Lung Oncology Group in Kyushu
      (LOGIK1004A).
AB  - BACKGROUND: Various polymorphisms have been detected in the UDP
      glucuronosyltransferase 1A ( UGT1A ) gene, and UGT1A1 *28 and UGT1A1 *6 have
      important effects on the pharmacokinetics of irinotecan and the risk of severe
      toxicities during irinotecan therapy. This study was conducted to determine the
      maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1
      genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1
      *6 polymorphism. METHODS: The eligibility criteria were as follows: lung cancer
      patients that had previously been treated with anticancer agents other than
      irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included
      *28/*28, *6/*6, and *28/*6, and group B included *28 /- and *6 /-), were aged
      <=75 years old, had a performance score of 0-1, and exhibited adequate bone
      marrow function. The patients were scheduled to receive irinotecan on days 1, 8,
      15, 22, 29, and 36. RESULTS: Four patients were enrolled in this trial. Two
      patients were determined to be ineligible. The remaining two patients, who
      belonged to group B, received an initial irinotecan dose of 60 mg/m2 , but did
      not complete the planned treatment because of diarrhea and leukopenia. Thus, in
      group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study
      was terminated in group A because of poor case recruitment. CONCLUSIONS: The MTD
      of irinotecan for previously treated lung cancer patients that are heterozygous
      for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2 .

PMID- 27883282
TI  - Obesity Week 2016 Annual Meeting.

PMID- 27883283
TI  - Usefulness of Transthoracic Echocardiography Parameters and Brain Natriuretic
      Peptide as Mortality Predictors in Hospitalized Acutely Poisoned Patients: A
      Prospective Observational Study.
AB  - Acute poisonings represent a common cause of morbidity and mortality worldwide.
      The prognostic utility of the transthoracic echocardiography (TTE) parameters
      combined with brain natriuretic peptide (BNP) in acute poisoning with different
      xenobiotics, upon admission in the hospital, was not evaluated. This prospective
      observational cohort study included 229 acutely poisoned non-diabetic adults,
      with a median age of 44 years (range 18-90 years), 50.7% women, with an in
      hospital mortality rate of 8.7%. Univariate logistic regression analysis showed
      that age, the left ventricle kinetic abnormalities, the E-wave deceleration time
      (EDT) and BNP correlated significantly with mortality in acutely poisoned
      patients. Multivariate logistic regression showed that only EDT [odds ratio (OR)
      3.44, 95% confidence interval (CI) 1.54-7.69, p 0.003], BNP (OR 1.61, 95% CI:
      1.02-2.55, p 0.04) and age (OR 2.66, 95% CI: 1.23-5.76, p 0.013) are predictive
      for mortality. The receiver-operating characteristic (ROC) analysis proved EDT
      [area under the ROC curve (AUC), 0.85; CI: 0.76-0.94; p 0.001], BNP (AUC, 0.83;
      CI: 0.75-0.91; p 0.001) and age (AUC, 0.82; CI: 0.74-0.90; p 0.001) as indicators
      for fatalities. In hospitalized patients acutely intoxicated with
      undifferentiated poisons, EDT as a parameter of left ventricle diastolic function
      and BNP are useful to early predict mortality.

PMID- 27883281
TI  - Severe mortality impact of the 1957 influenza pandemic in Chile.
AB  - INTRODUCTION: Epidemiological studies of the 1957 influenza pandemic are scarce,
      particularly from lower-income settings. METHODS: We analyzed the spatial
      temporal mortality patterns of the 1957 influenza pandemic in Chile, including
      detailed age-specific mortality data from a large city, and investigated risk
      factors for severe mortality impact across regions. RESULTS: Chile exhibited two
      waves of excess mortality in winter 1957 and 1959 with a cumulative excess
      mortality rate of 12 per 10 000, and a ~10-fold mortality difference across
      provinces. High excess mortality rates were associated with high baseline
      mortality (R2 =41.8%; P=.02), but not with latitude (P>.7). Excess mortality
      rates increased sharply with age. Transmissibility declined from R=1.4-2.1 to
      R=1.2-1.4 between the two pandemic waves. CONCLUSIONS: The estimated A/H2N2
      mortality burden in Chile is the highest on record for this pandemic-about three
      to five times as severe as that experienced in wealthier nations. The global
      impact of this pandemic may be substantially underestimated from previous studies
      based on high-income countries.

PMID- 27883285
TI  - Time- and strain-specific downregulation of intestinal EPAS1 via miR-148a by
      Bifidobacterium bifidum.
AB  - SCOPE: Bifidobacteria play a role in intestinal homeostasis but molecular
      mechanisms remain underinvestigated. The aim of this study was to assess if
      probiotic Bifidobacterium strains alter expression of intestinal microRNA and
      downstream target gene response. METHODS AND RESULTS: The expression of miR-148a
      and its validated target endothelial PAS domain protein 1 (EPAS1) was analyzed in
      Caco-2 cells and mice cecum in response to Bifidobacterium bifidum MIMBb75, B.
      bifidum NCC390, or Bifidobacterium longum NCC2705. In vitro, exposure to B.
      bifidum MIMBb75, but not to B. bifidum NCC390 or B. longum NCC2705, increased the
      expression of miR-148a after 1 and 4 h (p < 0.01), but not after 24 h. In vivo,
      B. bifidum MIMBb75 administration to C57BL/6J mice increased miR-148a expression
      in the cecum after 2 but not 14 days (p < 0.05). The increase in miR-148a was
      accompanied by a decrease in EPAS1 expression in Caco-2 cells and cecum (p <
      0.05). Silencing of miR-148a reversed B. bifidum MIMBb75 dependent downregulation
      of EPAS1. CONCLUSION: This study shows an early response of intestinal cells to
      B. bifidum MIMBb75 through miR-148a modulation. This brings a new concept of
      strain- and time-dependent bifidobacteria-host crosstalk via microRNA. Probiotic
      B. bifidum MIMBb75 may help attenuating EPAS1 overexpression associated with
      intestinal inflammation.

PMID- 27883284
TI  - Novel biomarkers of nasopharyngeal carcinoma metastasis risk identified by
      reverse phase protein array based tumor profiling with consideration of plasma
      Epstein-Barr virus DNA load.
AB  - PURPOSE: In patients with Epstein-Barr virus (EBV) associated nasopharyngeal
      carcinoma (NPC), intertumor heterogeneity causes interpatient heterogeneity in
      the risk of distant metastasis. We aimed to identify novel biomarkers of
      metastasis risk using reverse phase protein array (RPPA) profiling of NPC
      patients at risk for metastasis and considering plasma EBV DNA load. EXPERIMENTAL
      DESIGN: A total of 98 patients with NPC with and without metastasis after
      treatment, matched with respect to clinical parameters, are enrolled. Total
      protein expression is measured by RPPA, and protein functions are analyzed by
      pathway bioinformatics. RESULTS: The RPPA analysis revealed a profile of 70
      proteins that are differentially expressed in metastatic and nonmetastatic
      tumors. Plasma EBV DNA load after treatment correlated with protein expression
      level better than plasma EBV DNA load before treatment did. The biomarkers of NPC
      metastasis identified by proteomics regulate signaling pathways involved in cell
      cycle progression, apoptosis, and epithelial-mesenchymal transition. The authors
      identified 26 biomarkers associated with 5-year distant failure-free survival in
      univariate analysis; five biomarkers remained significant in multivariate
      analysis. CONCLUSIONS AND CLINICAL RELEVANCE: A comprehensive RPPA profiling
      study is warranted to identify novel metastasis-related biomarkers and further
      examine the activation state of signaling proteins to improve estimation of
      metastasis risk for patients with EBV-associated NPC.

PMID- 27883286
TI  - Influenza in Poland in 2013 and 2013/2014 epidemic season
AB  - OBJECTIVE: Analysis of epidemiological situation of influenza in Poland in 2013
      and 2013/14 epidemic season in reference to previous years and seasons. MATERIAL
      AND METHODS: Analysis was based on: 1) data collected within influenza routine
      surveillance system in Poland, including data published in annual bulletins
      "Infectious diseases and poisonings in Poland" as well as unpublished data
      gathered in the Department of Epidemiology of the NIPH-NIH; 2) data collected
      within influenza system - Sentinel, and beyond this system, concerning results of
      virological tests carried out in 2013/14 epidemic season in the Department of
      Influenza Research, National Influenza Center in the NIPHNIH and/or laboratories
      of provincial sanitary and epidemiological stations which are gathered in the
      National Influenza Center. RESULTS: Compared to 2012, the number of influenza and
      influenza-like cases increased more than twofold in 2013 in Poland. A total of 3
      164 405 cases were reported. Incidence was 8 218.7 per 100,000 population (33
      733.2 in 0-4 age group). As many as 0.45% of patients were referred to hospitals.
      According to the data of the Central Statistical Office, 115 deaths due to
      influenza were notified. Based on the data of the sanitary inspection (incomplete
      data), the percentage of population vaccinated against influenza was 2.4% (7.7%
      of persons aged more than 64 years). A total of 2 780 945 cases were registered
      in 2013/14 epidemic season. Its peak was reported in March 2014. Incidence was 7
      224.0 per 100,000 population (35 172.8 in 0-4 age group). Compared to 2012/13
      epidemic season, it was lower by 8.0%. Incidence rates ranged from 29 339.6 in
      pomorskie voivodeship to 1 306.5 in lubuskie voivodeship. Nearly a half of all
      cases (48.7%) were registered in children and adolescents up to 15 years. As many
      as 0.34% of patients were referred to hospitals (0.87% of persons aged more than
      64 years). From the data of the Central Statistical Office transpires that 8
      deaths due to influenza were reported in epidemic season. Type A influenza
      subtype H3N2 predominated in all influenza cases. Human respiratory syncytial
      virus (RSV) was the dominant agent in other viral infections of respiratory
      tract. Antigenic analysis of influenza strains showed their affinity with vaccine
      strains of the vaccine recommended for this epidemic season. CONCLUSIONS: In
      spite of slow improvements, influenza and influenza-like surveillance system in
      Poland is still not homogeneous and stable enough. It hinders the assessment of
      current epidemiological situation. For instance, there are difficulties in
      determining what is the effect of modifications in the surveillance on the
      increase in the number of influenza and influenza-like cases observed in Poland
      in recent years. A low percentage of population vaccinated against influenza
      (with a decreasing trend beginning from 2005) suggests a necessity of revising
      the methods of promotion and organization of these vaccines used so far. One of
      the public health priorities should be to increase the percentage of vaccinated
      population up to the average level in EU countries.

PMID- 27883288
TI  - Corrigendum.

PMID- 27883287
TI  - Definition, classification and retrospective analysis of photostimulable phosphor
      image artefacts and errors in intraoral dental radiography.
AB  - OBJECTIVES: To detect and determine image error and artefact types in intraoral
      radiographs obtained with photostimulable phosphor (PSP) technology, place them
      in an appropriate classification and retrospectively analyze the PSP-specific
      image errors and artefacts. The causes and solutions of PSP-specific errors and
      artefacts have also been discussed. METHODS: The radiographic database of Ondokuz
      Mayis University, Faculty of Dentistry, Department of Dentomaxillofacial
      Radiology, was used for this study. Different types of image errors and artefacts
      observed on intraoral radiographs during 2014-15 were detected and defined. A
      total of 2100 intraoral radiographs were individually evaluated for the
      distribution of PSP-specific image artefacts. RESULTS: There were 34 image error
      and artefact types detected and classified into 4 groups according to the
      causative factors. The most common PSP-specific image artefacts were found in
      fading with a ratio of 44.1% for the ambient light-related group, peeling of the
      plate borders with a ratio of 53.4% for the PSP plate-related group and straight
      line with a ratio of 42.2% for the scanner-related group. CONCLUSIONS: The
      determination and definition of the image errors and artefacts with clarification
      of their causes and solutions are important for the improvement of radiographic
      quality and the reduction of the retake ratio.

PMID- 27883289
TI  - Should CYP2D6 be genotyped when treating with tamoxifen?

PMID- 27883290
TI  - Behavioral evidence for a differential modulation of semantic processing and
      lexical production by aging: a full linear mixed-effects modeling approach.
AB  - The effect of normal aging on lexical production and semantic processing was
      evaluated in 72 healthy participants. Four tasks were used, picture naming (PN),
      picture categorization (PC), numerical judgment (NJ), and color judgment (CJ).
      The dependence of reaction time (RT) and correct responses with age was accounted
      by mixed-effects models. Participants underwent neuropsychological testing for
      verbal, executive, and memory functions. The RTs increase significantly with age
      for all tasks. After parceling out the non-specific cognitive decline, as
      reflected by the NJ task, the RT for the PN task decreases with age. Behavioral
      data were interpreted in relation with neuropsychological scores. Our results
      suggest that (a) naming becomes more automatic and semantic processing slightly
      more difficult with age, and (b) a non-specific general slowdown of cognitive
      processing occurs with age. Lexical production remained unaltered, based on
      compensatory automatic processes. This study also suggests a possible slowdown of
      semantic processing, even in normal aging.

PMID- 27883291
TI  - Pharmacogenomics of second-line drugs used for treatment of unresponsive or
      relapsed osteosarcoma patients.
AB  - Second-line treatment of high-grade osteosarcoma (HGOS) patients is based on
      different approaches and chemotherapy protocols, which are not yet standardized.
      Although several drugs have been used in HGOS second-line protocols, none of them
      has provided fully satisfactory results and the role of rescue chemotherapy is
      not well defined yet. This article focuses on the drugs that have most frequently
      been used for second-line treatment of HGOS, highlighting the present knowledge
      on their mechanisms of action and resistance and on gene polymorphisms with
      possible impact on treatment sensitivity or toxicity. In the near future,
      validation of the so far identified candidate genetic biomarkers may constitute
      the basis for tailoring treatment by taking the patients' genetic background into
      account.

PMID- 27883293
TI  - Psychological mislabeling of chronic pain: lessons from migraine in the 20th
      century.
AB  - Starting with Freud, psychoanalytically oriented practitioners described a
      complex of unconscious conflicts, desires and personality traits they believed to
      be the primary cause of a wide range of medical disorders. This was the
      psychogenic model. With the advance of basic research and pharmacotherapy, the
      psychogenic model was gradually replaced by a biopsychobehavioral model. This
      model treats chronic pain as a biologically based disorder that can be influenced
      by psychological factors and lifestyle. The present paper argues that many
      patients with chronic pain may not be significantly impacted by psychological
      factors, and that for those who are, cognitive-behavioral therapy is the
      treatment of choice.

PMID- 27883294
TI  - Drug discovery beyond the rule of 5 - Opportunities and challenges.

PMID- 27883292
TI  - IL1A rs1800587 associates with chronic noncrisis pain in sickle cell disease.
AB  - AIM: Pain is prevalent in sickle cell disease (SCD) patients who display great
      heterogeneity in pain severity and frequency. Hypothesizing that inflammatory
      factors are involved in the pathogenesis of SCD pain, we focused on the IL1A C/T
      polymorphism rs1800587 that is an SNP located in a cis-transcriptional regulatory
      region. METHODS: We genotyped IL1A rs1800587 and performed association studies
      with phenotype data obtained by a multidimensional pain assessment tool using the
      PAINReportIt(r) Questionnaire. RESULTS: Each T allele was associated with a 3.9
      increase in composite pain index score (p = 0.04) as determined by multiple
      linear regression. CONCLUSION: IL1A rs1800587 may influence chronic pain in SCD.

PMID- 27883296
TI  - Adjuvant trastuzumab: a 10-year overview of its benefit.
AB  - INTRODUCTION: Anti-HER2 targeted therapy is one of the key advances in the
      treatment of breast cancer that have occurred in the last 20 years. In the
      adjuvant setting, the use of trastuzumab has led to prolonged and sustained
      survival benefit with very little toxicity as also confirmed by the 10-year
      follow-up results from the pivotal trials. Despite the survival improvement,
      several key issues are not entirely resolved in this field. These issues have led
      to multiple research efforts in de-escalating or escalating the standard
      treatment with chemotherapy and 1 year of adjuvant trastuzumab. Areas covered: In
      this paper, we present an in depth overview on the state of the art on these key
      issues of refining decision-making in adjuvant anti-HER2 therapy. Expert
      commentary: Despite many important research efforts in the field, chemotherapy
      plus trastuzumab for a total duration of 1 year remains the standard of care.
      However, recent data showed that besides standard anthracycline- and taxane-based
      cytotoxic therapy, alternative chemotherapy regimens can now be proposed to
      patients with small tumors without nodal involvement and to women at high-risk of
      developing cardiotoxicity. Of note, besides HER2 itself, biomarkers predicting
      patients who may truly benefit from anti-HER2 agents are still lacking.

PMID- 27883295
TI  - Identification of novel SNPs associated with risk and prognosis in patients with
      castration-resistant prostate cancer.
AB  - AIM: Metabolism and transport play major roles in life-long exposure to
      endogenous and exogenous carcinogens. We therefore explored associations between
      polymorphisms in absorption, distribution, metabolism and elimination genes and
      the risk and prognosis of castration-resistant prostate cancer (CRPC). MATERIALS
      & METHODS: A total of 634 genotypes were tested in 74 patients using the
      Affymetrix DMETv1.0 platform. RESULTS: No relation to risk was found. Three SNPs
      were associated with CRPC prognosis in Caucasians: ABCB11 rs7602171G>A (p =
      0.003; n = 30; hazard ratio [HR]: 0.307), GSTP1 rs1799811C>T (p = 0.001; n = 38;
      HR: 0.254) and SLC5A6 rs1395 (p = 0.004; n = 35; HR: 3.15). Two other
      polymorphisms among Caucasians were associated with interesting trends: ABCB4
      rs2302387C>T (p = 0.039) and ABCC5 rs939339A>G (p = 0.018). CONCLUSION: This
      exploratory study is the first to show that polymorphisms in several absorption,
      distribution, metabolism and elimination genes may be associated with CRPC
      prognosis.

PMID- 27883297
TI  - Patients' perception of Parkinson's disease-associated pain following initiation
      of rotigotine: a multicenter non-interventional study.
AB  - OBJECTIVES: To evaluate Parkinson's disease (PD)-associated pain as perceived by
      the patients (subjective characterization), and how this may change following
      initiation of rotigotine transdermal patch. METHODS: SP1058 was a non
      interventional study conducted in routine clinical practice in Germany and
      Austria in patients experiencing PD-associated pain (per the physician's
      assessment). Data were collected at baseline (ie, before rotigotine initiation)
      and at a routine visit after >=25 days (-3 days allowed) of treatment on a
      maintenance dose of rotigotine (end of study [EoS]). Pain perception was assessed
      using the 12-item Pain Description List of the validated German Pain
      Questionnaire (each item ranked 0 = 'not true' to 3 = 'very true'). Primary
      effectiveness variable: change from baseline to EoS in the sum score of the 4
      'affective dimension' items of the Pain Description List. Secondary effectiveness
      variables: change from baseline to EoS in Unified Parkinson's Disease Rating
      Scale (UPDRS) II, III, and II+III scores, and Parkinson's Disease Questionnaire
      (PDQ-8) total score (PD-related quality-of-life). Other variables included scores
      of the eight 'sensory dimension' items of the Pain Description List. RESULTS: Of
      93 enrolled patients (mean [SD] age: 71.1 [9.0] years; male: 48 [52%]), 77 (83%)
      completed the study, and 70 comprised the full analysis set. The mean (SD) change
      from baseline in the sum score of the four 'affective dimension' items was -1.3
      (2.8) indicating a numerical improvement (baseline: 3.9 [3.4]). In the 'sensory
      dimension', pain was mostly perceived as 'pulling' at baseline (49/70 [70%]);
      'largely true'/'very true'). Numerical improvements were observed in all UPDRS
      scores (mean [SD] change in UPDRS II+III: -5.3 [10.5]; baseline: 36.0 [15.9]),
      and in PDQ-8 total score (-2.0 [4.8]; baseline: 10.7 [5.9]). Adverse drug
      reactions were consistent with dopaminergic stimulation and transdermal
      administration. CONCLUSION: The perception of the 'affective dimension' of PD
      associated pain numerically improved in patients treated with rotigotine.
      ClinicalTrials.gov identifier: NCT01606670;
      https://clinicaltrials.gov/ct2/show/NCT01606670?term=NCT01606670&rank=1.

PMID- 27883298
TI  - How Should Physicians Refer When Referral Options are Limited for Transgender
      Patients?
AB  - Transgender people encounter many barriers to health care, and recommendations
      about where their treatment would best be offered can promote or thwart good
      care. This case examines the care setting from the perspective of a patient whose
      experiences with specialists have been negative. We argue that an ethos of harm
      reduction and informed consent, with a strong emphasis on continuity of care
      within a primary care setting, should guide questions about how to refer
      transgender patients to caregivers and to good care settings.

PMID- 27883300
TI  - Should Psychiatrists Prescribe Gender-Affirming Hormone Therapy to Transgender
      Adolescents?
AB  - Gender-affirming hormone therapy is a safe and effective way to improve quality
      of life and mental health outcomes for transgender adolescents. Access to this
      treatment is limited, with the most vulnerable transgender people experiencing
      the greatest gaps in care. Because some psychiatrists help transgender patients
      receive needed medical interventions, we analyze the ethical values they must
      balance when deciding whether to provide hormone therapy to patients who seek it.

PMID- 27883299
TI  - Should Mental Health Screening and Psychotherapy Be Required Prior to Body
      Modification for Gender Expression?
AB  - Some people want to modify their bodies through hormonal and surgical treatments
      in order to resolve gender dysphoria, the distress they experience when their
      bodies do not align with their gender identity. The World Professional
      Association for Transgender Health (WPATH) offers guidelines to clinicians
      regarding treatment of people wanting to modify their bodies for this reason.
      Prior to these modifications, WPATH advises that mental health screening is
      needed and that psychotherapy is recommended though not a requirement. In fact,
      these advisories allow clinicians some freedom in applying the standards to
      specific cases. Although some variation from the WPATH Standards of Care can be
      clinically acceptable, informed consent remains an essential component of
      clinical encounters involving body modifications.

PMID- 27883301
TI  - What's in a Guideline? Developing Collaborative and Sound Research Designs that
      Substantiate Best Practice Recommendations for Transgender Health Care.
AB  - Transgender medicine presents a particular challenge for the development of
      evidence-based guidelines, due to limitations in the available body of evidence
      as well as the exclusion of gender identity data from most public health
      surveillance activities. The guidelines that have been published are often based
      on expert opinion, small studies, and data gathered outside the US. The existence
      of guidelines, however, helps legitimate the need for gender-affirming medical
      and surgical interventions. Research conducted on transgender populations should
      be grounded in gender-affirming methodologies and focus on key areas such as
      health outcomes after gender-affirming interventions.

PMID- 27883302
TI  - Affirmative and Responsible Health Care for People with Nonconforming Gender
      Identities and Expressions.
AB  - Although recent changes in health care delivery have improved routine and gender
      affirming care for transgender people, common approaches to care are still often
      based on a binary (i.e., male/female) gender framework that can make patients
      with gender-nonconforming (GNC) identities and expressions feel marginalized.
      Binary representation perpetuates invisibility, discrimination, and victimization
      and subsequent poorer health-among GNC patients. In response, clinicians and
      health care systems should extend their efforts to provide gender-affirming and
      responsible care to GNC people. This article reviews terminology related to
      gender, the limited research-and necessary directions for future research-on GNC
      communities, and provides strategies for health care professionals and systems to
      ensure provision of gender-affirming and responsible care to GNC patients.

PMID- 27883303
TI  - Transgender Reproductive Choice and Fertility Preservation.
AB  - Increasing numbers of young transgender people are now using medical technologies
      to achieve a physical gender transition. However, the procedures of physical
      gender transition might cause temporary or permanent sterility. Thus many
      transgender people are now using fertility preservation technologies.
      Nonetheless, they can experience dilemmas in making reproductive and family
      building decisions and face challenges in gaining access to and utilizing
      fertility preservation services. Based on qualitative research conducted with
      transgender men and women who used reproductive technologies for preserving their
      fertility before or during their physical transition, this paper contributes to
      the discourse of reproductive choice by the inclusion of transgender people's
      experience.

PMID- 27883304
TI  - Transgender Rights as Human Rights.
AB  - Arguments to support transgender rights often rely on "born that way" arguments,
      which assert that gender identity is innate, immutable, and unassociated with
      choice. These arguments are vulnerable to attack on several grounds, including on
      the basis of emerging scientific data. Stronger support for transgender rights
      arises from human rights arguments.

PMID- 27883305
TI  - Understanding Transgender and Medically Assisted Gender Transition: Feminism as a
      Critical Resource.
AB  - Feminism has fought the trivialization of women's experiences, championed women's
      security, and insisted on respect for women's choices. In so doing, feminism has
      developed important perspectives on the complicated connections between what
      gender means as it plays itself in people's lives, and the inequalities of power
      and authority that structure much of human experience. Here, I put a few of these
      perspectives into contact with an issue where the interactions of gender and
      power are squarely in play: medicine's role in assisting gender transitioning
      generally and, specifically, the enduring controversy between medicine and many
      transgender people about the pathologization of transgender and the role of
      clinicians as gatekeepers to gender-transition interventions.

PMID- 27883306
TI  - Lessons from a Transgender Patient for Health Care Professionals.
AB  - It is not uncommon for transgender patients to avoid sharing information about
      their identity and medical history with health care professionals, due to past
      negative experiences within health care settings. Professionals who show
      sensitivity to the topic and express care about health record documentation can
      increase a transgender patient's trust. There are many opportunities to increase
      transgender health literacy, including consultation, conferences, webinars,
      books, and articles focused on transgender health care. It's critical for
      professionals to listen closely to individual patients' stated needs. This
      article shares one transgender patient's encounters and experiences within health
      care settings and offers lessons on how health care professionals can be more
      inclusive, respectful, and responsive to the needs of transgender patients.

PMID- 27883307
TI  - Informed Consent in the Medical Care of Transgender and Gender-Nonconforming
      Patients.
AB  - Informed consent as a model of care has evolved as an alternative to the standard
      model of care recommended by the World Professional Association for Transgender
      Health's Standards of Care, version 7, which emphasizes the importance of mental
      health professionals' role in diagnosing gender dysphoria and in assessing the
      appropriateness and readiness for gender-affirming medical treatments. By
      contrast, the informed consent model for gender-affirming treatment seeks to
      acknowledge and better support the patient's right to, and capability for,
      personal autonomy in choosing care options without the required involvement of a
      mental health professional. Clinicians' use of the informed consent model would
      enable them both to attain a richer understanding of transgender and gender
      nonconforming patients and to deliver better patient care in general.

PMID- 27883308
TI  - Response to "Ethical and Clinical Dilemmas in Using Psychotropic Medications
      During Pregnancy".

PMID- 27883309
TI  - Likely impact of pre-exposure prophylaxis on HIV epidemics among men who have sex
      with men.
AB  - Rapid developments in the field of HIV pre-exposure prophylaxis (PrEP) with
      antiretrovirals offer a promise to bring HIV transmission among gay and other men
      who have sex with men (MSM) to zero by 2030. This review evaluates studies, which
      modelled the impact of PrEP on HIV diagnoses, and discusses the progress towards
      PrEP implementation. Studies in English, conducted after 2010 among MSM in
      countries of the Organization for Economic Cooperation and Development (OECD)
      were reviewed. Six modelling studies were included, three of which had been
      conducted outside the US. None of the published models showed that PrEP alone can
      reduce HIV diagnoses to zero and eliminate HIV transmission by 2030. However,
      PrEP in combination with other biomedical interventions can reduce HIV diagnoses
      on the population level by ~95%. Other upcoming biomedical prevention strategies
      may strengthen combination prevention. Access to PrEP remains limited, even in
      the OECD countries. Modelling studies can assist governments with decision-making
      about PrEP implementation and add urgency to the implementation of PrEP. More
      work is needed on modelling of the impact of PrEP on HIV diagnoses trends outside
      the US where PrEP implementation is in its early stages.

PMID- 27883310
TI  - Daily diary study of adult men's and women's event-level sexual motivations and
      sexual behaviour.
AB  - : Background Understanding people's sexual motivations has long been of public
      health and health promotion interest. We used daily diaries to examine how adult
      men's and women's event-specific affective sexual motivations were linked to the
      types and combinations of sexual behaviours chosen in a given sexual event.
      METHODS: Adult men (n=156) and women (n=192) completed thrice-daily electronic
      diaries assessing individual- and partner-specific attributes and non-coital or
      coital sexual behaviours. Sexual motivations were: interest in sex, feeling in
      love with partner, wanted to have sex and partner wanted to have sex. The outcome
      variable was: sexual behaviour type (no sex, one vaginal sex event, one vaginal
      sex event+any other sex types, multiple vaginal sex events, any other sex types).
      Mixed-effect multinomial logistic regression modelled the influence of each
      sexual motivation on sexual behaviour type (Stata; all p<0.05). 'No sex' was the
      referent in all models; all models controlled for gender. RESULTS: Participants
      contributed 14856 total partner-associated diary entries. Most (54%; women:
      56.5%, men: 51.2%) were associated with no sex; when sex occurred, the most
      common behaviour type was one vaginal sex event (13.1%) for women and other sex
      types (16.4%) for men. Wanting to have sex or perceiving a partner wanted to have
      sex were the strongest predictors of sexual behaviour type, and were associated
      with a greater number of reported sexual behaviours. CONCLUSIONS: Event-specific
      sexual motivations are associated with the choice to have sex, and with variation
      in the chosen sexual behaviours.

PMID- 27883311
TI  - HIV testing self-efficacy is associated with higher HIV testing frequency and
      perceived likelihood to self-test among gay and bisexual men.
AB  - : Background Regular testing of individuals at higher-risk of HIV is central to
      current prevention strategies. The aim of the present study was to examine the
      extent to which confidence in one's perceived ability to undertake various
      aspects of HIV testing and self-testing (self-efficacy) affected HIV testing
      outcomes. We assessed factors, including self-efficacy, associated with HIV
      testing frequency and the likelihood to self-test among gay and bisexual men
      (GBM). METHODS: Participants were HIV-negative GBM at an increased risk of HIV
      (more than five partners or condomless anal intercourse in the previous 3 months)
      enrolled in a randomised controlled trial of HIV self-testing. The baseline
      questionnaire captured data regarding sociodemographic characteristics, HIV
      and/or sexually transmissible infection testing history, sexual behaviour,
      beliefs and attitudes towards HIV and eight items capturing confidence in HIV
      testing ability that were combined as a single broad measure of HIV testing self
      efficacy (alpha=0.81). Factors associated with three or more HIV tests in the
      past year and the likelihood of self-testing in the future were determined using
      logistic regression. RESULTS: Of 354 GBM, 34% reported three or more HIV tests in
      the past year, and 64% reported being 'very likely' to self-test. Factors
      independently associated with three or more HIV tests in the past year were:
      higher self-efficacy (adjusted odds ratio (aOR) 1.08 per unit increase; 95%
      confidence interval (CI) 1.02-1.14; P=0.004); >10 male partners in the past 6
      months (aOR 1.79; 95% CI 1.05-3.04; P=0.031) and higher optimism regarding the
      effects of HIV treatments on HIV transmission (aOR 1.14; 95% CI 1.00-1.29;
      P=0.044). Only higher self-efficacy was independently associated with reporting a
      greater likelihood to self-test in the future (aOR 1.10; 95% CI 1.05-1.15; P <
      0.001). CONCLUSIONS: Improving self-efficacy by enhancing GBM's knowledge and
      experience may lead to higher testing frequency. The self-efficacy measure used
      in the present study could be useful in identifying GBM likely to face
      difficulties with HIV testing and self-testing.

PMID- 27883313
TI  - What Should be the Appropriate Referral to the Nephrologists - Do we have the
      Data?

PMID- 27883314
TI  - Diagnostic and Surgical Approach to Prenatally Detected Urinary Tract Anomalies.
AB  - Regular ultrasound examinations carried out in the second trimester of pregnancy
      help in detecting many anomalies in the fetal urinary tract. Their percentage
      ranges from 1% to 3% of all controlled pregnancies. There is a wide spectrum of
      anomalies that affect the urinary tract, but the most significant are:
      uretero/hydronephrosis (unilateral or bilateral), kidney agenesis, dysplastic
      kidney, polycystic and multicystic kidneys, anomalies of ascent, anomalies of
      kidney rotation or fusion, bladder exstrophy, posterior urethra valve etc. Many
      of these anomalies do not have impact either on urine flow or on kidney function
      and hence they can be qualified rather as a condition than as a disease. At the
      same time, most of the hydronephroses that are seen prenatally are being resolved
      spontaneously, and they are not detected neither presented postnatally as
      uretero/hydronephroses of unobstructed type and do not require surgical
      treatment. Only one tenth of these anomalies are subject to active surgical
      treatment. Therefore, the assessment of these conditions should be done by a
      specialized team, who will make adequate therapeutic decisions based on clinical
      guidelines, as well as will advise the parents on the future clinical
      implications of the detected anomaly.

PMID- 27883312
TI  - Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae
      Hypoxic Response.
AB  - Many cells experience hypoxia, or low oxygen, and respond by dramatically
      altering gene expression. In the yeast Saccharomyces cerevisiae, genes that
      respond are required for many oxygen-dependent cellular processes, such as
      respiration, biosynthesis, and redox regulation. To more fully characterize the
      global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA
      at different times, and performed RNA sequencing (RNA-seq) analysis. Time-course
      statistical analysis revealed hundreds of genes that changed expression by up to
      550-fold. The genes responded with varying kinetics suggesting that multiple
      regulatory pathways are involved. We identified most known oxygen-regulated genes
      and also uncovered new regulated genes. Reverse transcription-quantitative PCR
      (RT-qPCR) analysis confirmed that the lysine methyltransferase EFM6 and the
      recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking
      more broadly, oxygen-regulated genes participate in expected processes like
      respiration and lipid metabolism, but also in unexpected processes like amino
      acid and vitamin metabolism. Using principle component analysis, we discovered
      that the hypoxic response largely occurs during the first 2 hr and then a new
      steady-state expression state is achieved. Moreover, we show that the oxygen
      dependent genes are not part of the previously described environmental stress
      response (ESR) consisting of genes that respond to diverse types of stress. While
      hypoxia appears to cause a transient stress, the hypoxic response is mostly
      characterized by a transition to a new state of gene expression. In summary, our
      results reveal that hypoxia causes widespread and complex changes in gene
      expression to prepare the cell to function with little or no oxygen.

PMID- 27883315
TI  - The Need for Accurate Risk Prediction Models for Road Mapping, Shared Decision
      Making and Care Planning for the Elderly with Advanced Chronic Kidney Disease.
AB  - As people age, chronic kidney disease becomes more common, but it rarely leads to
      end-stage kidney disease. When it does, the choice between dialysis and
      conservative care can be daunting, as much depends on life expectancy and
      personal expectations of medical care. Shared decision making implies adequately
      informing patients about their options, and facilitating deliberation of the
      available information, such that decisions are tailored to the individual's
      values and preferences. Accurate estimations of one's risk of progression to end
      stage kidney disease and death with or without dialysis are essential for shared
      decision making to be effective. Formal risk prediction models can help, provided
      they are externally validated, well-calibrated and discriminative; include
      unambiguous and measureable variables; and come with readily applicable equations
      or scores. Reliable, externally validated risk prediction models for progression
      of chronic kidney disease to end-stage kidney disease or mortality in frail
      elderly with or without chronic kidney disease are scant. Within this paper, we
      discuss a number of promising models, highlighting both the strengths and
      limitations physicians should understand for using them judiciously, and
      emphasize the need for external validation over new development for further
      advancing the field.

PMID- 27883316
TI  - To Accept or Refuse Patient's Gift in Money? and How? - Case Report with Review.
AB  - This report describes a (rare) situation when a patient's first gift to a young
      doctor was in money. This happened in very specific circumstances - in a refugee
      camp during the War in Croatia. The data are taken from a large study on gifts,
      conducted on a representative sample of Croatian general practitioners (GPs), N =
      265, from 2358 in total. Pro and contra factors are discussed, considering
      tradition and customs, but also a lack of knowledge of young doctors in handling
      gifts in general. The intention of this report is primarily educative, with
      review of (scarce) literature, and recommendations, where the generally accepted
      rules might have exceptions.

PMID- 27883317
TI  - Somatoform Disorders - A Pediatric Experience.
AB  - Somatization in children consists of the persistent experience and complaints of
      somatic distress that cannot be fully explained by a medical diagnosis. Working
      at the Psychophysiological Department at the University Clinic we are dealing
      with more than 100 children per year manifesting this kind of disorders. The aim
      of this article is to summarize some specific characteristics of the somatoform
      disorder in a group of 243 children, mean age 10.31 (+/- 2.75) years for both
      genders, selected randomly. The used psychometric instruments are: CBCL, EPQ for
      children, and MMPI-201 for mothers. The obtained results showed high scores for
      somatization, extroversion and accentuated anxiety for children; as well as a
      typical Hs-Hy personality profile for mothers. The treatment with cognitive
      behavior therapy and biofeedback showed very positive outcome.

PMID- 27883318
TI  - Maternal Lipids May Predict Fetal Growth in Type 2 Diabetes Mellitus and
      Gestational Diabetes Mellitus Pregnancies.
AB  - AIM: During diabetic pregnancy, complex metabolic changes occur in the lipid
      profile. The aim of the study was to determine the predictive values of maternal
      serum lipid levels on large-for-gestational age newborns during the third
      trimester in pregnancies of women with type 2 diabetes mellitus (DM2) and
      gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Data of forty three
      pregnancies of women with DM2 and two hundred women with GDM were analyzed. The
      analysis encompassed the following parameters: age, body mass index (BMI), lipid
      parameters, HbA1c in first, second and third trimester of pregnancy, preeclampsia
      and baby birth weight. RESULTS: DM2 and GDM groups showed statistically
      significant differences in the following variables: total lipids, triglycerides,
      total cholesterol, BMI, age, baby birth weight, incidence of SGA and preterm
      delivery (9.4 +/- 2.3 vs. 11.0 +/- 2.3 mmol/L, 2.4 +/- 1.4 vs. 3.4 +/- 1.6
      mmol/L, 5.5 +/- 1.2 vs. 6.4 +/- 1.4 mmol/L, 30.6 +/- 5.4 vs. 26.9 +/- 5.2 kg/m2,
      34 +/- 7.8 vs. 31.5 +/- 5.6 years, 3183 +/- 972 vs. 3533 +/- 699 g., 20% vs.
      7.5%, 27.9 vs. 14%, respectively, p < 0.05). Linear multiple regression analysis
      demonstrated that triglycerides, LDL-C and total cholesterol were independent
      predictors of LGA (p < 0.05). CONCLUSION: Triglycerides and LDL-C in the third
      trimester of pregnancy are independent predictors for fetal macrosomia in DM2 and
      GDM pregnancies. Thus, the maternal serum triglycerides and LDL-C levels
      determined in the maternal blood taken in the third trimester of pregnancy may
      indentify women who will give birth to LGA newborns.

PMID- 27883319
TI  - The Effects of Hormonal Therapy and Exercise on Bone Turnover in Postmenopausal
      Women: A Randomised Double-Blind Pilot Study.
AB  - INTRODUCTION: Hormone replacement therapy (HRT) and walking were investigated
      independently and in combination, to determine which treatment provided most
      effect on bone turnover in postmenopausal women. METHODS: Using a randomised
      double-blind pilot study, 10 subjects received HRT (transdermal estradiol, 50
      MUg/day and oral MPA 5 mg/day) and 12 received placebo for 20 weeks. Following a
      baseline period of treatment, both groups undertook a graduated walking regimen,
      which increased in intensity, duration and frequency parameters from weeks 8-20.
      Measurements of aerobic capacity, female sex hormones, bone formation markers
      [osteocalcin (OC) and bone alkaline phosphatase (BAP)] and bone resorption
      markers [deoxypyridinoline (DPD) and pyridinoline (PYR)] were measured at
      baseline (T1), week 8 (T2) and week 20 (T3). RESULTS: Age, time of postmenopause,
      weight or body mass index were no different between each groups. The HRT group
      had significantly higher estradiol levels compared with the placebo group at T2
      and T3. FSH and LH levels were significantly reduced following HRT. DPD and PYR
      were significantly reduced from baseline levels at T2 and T3 with HRT. No
      significant changes occurred in OC or BAP levels with either HRT or walking.
      Walking did not change bone turnover markers in either the HRT or placebo group.
      CONCLUSION: HRT reduces bone resorption, however, walking alone at the intensity
      and duration prescribed, or the combination of HRT and walking, provided no
      additional benefit after menopause. Therefore, HRT, but not walking is an
      effective treatment in reducing bone turnover in postmenopause women.

PMID- 27883320
TI  - Successful Kidney Transplantation in a Patient with Multiple Perioperative Renal
      Transplant Complications. Case Report.
AB  - Kidney transplantations have become common surgical procedures that are
      associated with high success rates. Nevertheless, the detection, accurate
      diagnosis and timely management of the perioperative surgical complications
      sometimes require multidisciplinary team approach for some of the complications
      may result in significant morbidity, risk of graft loss and/or mortality of the
      recipient. A case of a 24-year old male patient that developed a number of
      different surgical complications is reported. The complications included venous
      graft thrombosis, urinary fistula, wound infection, wound dehiscence and a
      completely exteriorized transplanted kidney. Despite the various complications
      and, accordingly, a couple of revisions, finally the patient was discharged with
      a regular kidney function.

PMID- 27883321
TI  - Body Size and Outcomes in Dialysis and Transplant Patients - Does it Matter?
AB  - The terminologies of "body size", "body mass index (BMI)", "body weight", "large
      BMI" and "obesity" are controversial for defining the effects of "adiposity" or
      "fat excess" on the outcomes of dialysis and transplant patients. However,
      probably these terminologies will be continued to be used in the future as well,
      because of being older and simpler terminologies. In the general population
      obesity is a powerful risk factor for cardiovascular morbidity and mortality,
      while, it conferred a survival advantage to dialysis patients. However, this may
      be a oversimplification, since obesity may still be a risk factor in non
      sarcopenic hemodialysis patients. Obesity is associated with early post
      transplant adverse effects (i.e. delayed graft function, graft failure, wound
      infections, also transplant costs) and unfavorable graft and patient survival.
      However, thanks to safer immunosuppressive protocols, recently graft and patient
      survival is similar in obese as those of the non-obese patients. On the other
      hand, morbid obesity may still be a cause of unfavorable patient and graft
      survival. Since obese transplant recipients have better life expectancy as
      compared to wait-listed hemodialysis patients, they should be transplanted as
      well, while morbidly obese patients should be asked to lose weight before being
      placed in the waiting lists.

PMID- 27883322
TI  - Molecular Biology and Genetic Mechanisms in the Progression of the Malignant Skin
      Melanoma.
AB  - Malignant skin melanoma is a tumor deriving from transformed skin melanocytes as
      a result of complex interactions between genetic and environmental factors. This
      melanoma has a potential to metastasize early and very often it is resistant to
      the existing modalities of the systemic therapy. As in any other neoplasms,
      certain types of melanoma may skip certain stages of progression. The progression
      from one stage to another is accompanied by specific biological changes. Several
      key changes in the melanoma tumorogenesis influence the regulation of the cell
      proliferation and vitality, including the RAS-RAF-ERK, PI3K-AKT, and
      p16INK4/CDK4/RB pathways. A key role in the dissreguarity of the RAS-RAF-ERK
      (MAPK) pathway in the malignant melanoma development have been demonstrated by
      many studies. To date, the molecular genetic alterations during melanoma
      development have been partially known. In the pathogenesis of the malignant
      melanoma, there are mutations of various genes such as NRAS, BRAF, and PTEN and
      mutations and deletions of CDKN2A. In the past years, great advance has been made
      in the insights of the molecular aspects of the melanoma pathogenesis. However,
      this field yet poses a challenge to discover new details about the melanoma
      molecular characteristics. The research results are focused towards the
      improvement of the melanoma patients prognosis by introducing personalized
      targeted therapy.

PMID- 27883323
TI  - Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid
      Sensitivity in Treatment of Postoperative Pain.
AB  - BACKGROUND: The minimal effective analgesic concentration of opioids required for
      satisfactory analgesia may differ significantly among the patients. Genetic
      factors may contribute to the variable response to opioids by affecting their
      pharmacokinetics or pharmacodynamics. METHODS: Ninety nine patients undergoing
      abdominal surgery with colorectal anastomosis because of colorectal carcinoma
      were enrolled in the present study. C34535T was genotyped in all subjects and the
      patients were divided into three groups according to their genotype: CC-wild type
      homozygous, CT-mutant heterozygous and TT-mutant homozygous. Intravenous
      fentanyl, patient controlled analgesia was provided postoperatively for pain
      control in the first 24 hour after surgery. Opioid consumption, pain scores and
      the adverse side effects were evaluated. RESULTS: Our main result is that the
      patients in the CC genotype group consumed significantly more fentanyl (375.0 MUg
      +/- 43.1) than the patients in the TT group (295.0 MUg +/- 49.1) and the CT
      (356.4 MUg +/- 41.8) group in the treatment of postoperative pain. The patients
      in the TT group had lower VAS scores at 6h, 12h, 18 h and 24h postoperatively.
      There were no significant differences in the side effects among the three groups
      regarding the vomiting and the sedation score. The patients in the TT group had
      more frequently nausea score 1, than the patients in the other two groups.
      CONCLUSION: Our study indicates that the C3435T SNPs of the ABCB1 gene is
      associated with differences in the opioid sensitivity. The ABCB1 polymorphism may
      serve as an important genetic predictor to guide the acute pain therapy in
      postoperative patients.

PMID- 27883324
TI  - Hormone Therapy Reduces Bone Resorption but not Bone Formation in Postmenopausal
      Athletes.
AB  - INTRODUCTION: Independently, hormone therapy and exercise have well-established
      protective effects on bone parameters. The combined effects of hormone therapy
      and exercise, however, are less clear. We, therefore, examined the effects of
      hormone therapy on bone turnover markers in postmenopausal women undergoing
      regular high intensity exercise. METHODS: In a randomised, double blind study,
      postmenopausal athletes competing at Masters level, received either hormone
      therapy (50 MUg transdermal oestradiol, 5 mg MPA, n = 8) or placebo (n = 7) for
      20 weeks. Women were tested before and after treatment for plasma concentrations
      of oestradiol, FSH, LH, and serum bone formation marker -osteocalcin (OC); and
      urine bone resorption markers-pyridinoline (PYD) and deoxypyridinoline (DPD).
      RESULTS: As a result of treatment with hormone therapy there were significant
      reductions in levels of FSH (73.3 +/- 13.7 to 48.6 +/- 10.5 mmol/L, p = 0.01) and
      bone resorption markers (PYD, 81.9 +/- 7.7 to 57.8 +/- 3.7 nmol/mmol Cr, p =
      0.001, and DPD, 18.5 +/- 3.1 to 11.8 +/- 2.1 nmol/mmol Cr, p = 0.01). Oestradiol
      and bone formation markers were not significantly altered as a result of hormone
      therapy. There were no changes to any variables with placebo treatment.
      CONCLUSION: Hormone therapy reduced bone resorption, but not bone formation, in
      postmenopausal athletes. These favorable reductions in bone turnover; therefore,
      provide an effective treatment in combination with high intensity exercise to
      further reduce the subsequent risk of osteoporosis and associated fractures.

PMID- 27883325
TI  - Solitary Fibrous Tumor of the Pancreas: A Case Report and Review of the
      Literature.
AB  - Pancreas is an extremely rare abdominal localization of the solitary fibrous
      tumor (SFT). It usually grows asymptomatically for a long time before a diagnosis
      can be made on the basis of symptoms and/or mechanical complications. Due to the
      rarity and nonspecific clinical presentation, this entity is diagnostically
      challenging. We present a 47-year-old man with a history of progressive
      epigastric pain for the last two weeks, and jaundice, who was admitted to
      hospital for further investigation. Cystadenocarcinoma was suspected based on the
      radiologic findings, and a pancreatoduodenectomy was performed. The removed
      portion of the pancreas contained a 3.5 * 2 * 1.8 cm well-circumscribed, but not
      encapsulated white tumor mass with smooth cut surface, cystic component and duct
      dilatation within the tumor and within the adjacent pancreatic tissue. Based on
      the histology and immunostaining profile, a diagnosis of the solitary fibrous
      tumor was made. One week post-operatively, the patient died due to surgical
      complications. Microscopic and immunohistochemical examinations are necessary for
      accurate diagnosis of cystic SFT of the pancreas. Because there is limited data
      regarding the biological behavior of SFT with extra-pleural localization the
      authors recommend clinical follow-up for SFT treatment if the criteria of
      malignancy are not met.

PMID- 27883326
TI  - Renal Replacement Therapy in Patients with Heart and Kidney Failure.
AB  - The incidence of chronic kidney disease (CKD) in patients with chronic heart
      failure (CHF) is high as CKD and CHF share underlying risk factors such as
      arterial hypertension, diabetes mellitus and atherosclerosis. Cardiac failure
      leads to renal hypoperfusion and dysfunction and then fluid overload and need for
      aggressive diuretic therapy. However, development of diuretic resistance
      represents a significant problem in the management of these patients. The role of
      Renal Replacement Therapy (RRT) is important for patients who do not response to
      conservative management of fluid overload facilitating the failing heart to
      restore function. According to the guidelines, venovenous isolated
      Ultrafiltration (UF) is indicated for patients with refractory congestion not
      responding to medical therapy with loop diuretics and infusion of dopamine. A
      systematic review of randomized controlled trials on the effect of UF vs. IV
      furosemide for decompensated heart failure showed a benefit of UF on total body
      weight loss and on readmissions due to heart failure in patients with
      decompensated heart failure and CKD. Peritoneal dialysis (PD) can provide
      efficient ultrafiltration and sodium extraction in volume overloaded patients
      followed by decline of hospitalization days, decrease of body weight and
      improvement of LVEF in patients with refractory heart failure. The continuous
      draw of ultrafiltrate is followed by a lesser risk of abrupt hypotension and
      better preservation of the residual kidney function. This represents a
      significant advantage of PD over intermittent UF by dialysis. In conclusion,
      application of UF by dialysis and PD is followed by significant total body weight
      loss, reduced need for hospital readmissions and better quality of life. PD has a
      higher probability of preservation of residual kidney function and can be used by
      patients at home.

PMID- 27883327
TI  - The Role of Serum Coagulation Factors in the Differential Diagnosis of Patients
      with Pneumonia and Parapneumonic Effusion.
AB  - The aim of this study was to identify the participations of the serum
      coagulations and fibrinolysis factors that contribute to the differential
      diagnosis of the patients with community-acquired pneumonia (CAP) without
      effusion, uncomplicated parapneumonic effusion (UCPPE) and complicated
      parapneumonic effusion (CPPE). The coagulations system is fundamental for the
      maintenance of homeostasis, and contributes to the inflammatory process
      responsible for CAP and the parapneumonic effusion. The factors of coagulations
      and fibrinolysis participate in the cellular proliferation and migration as in
      the synthesis of the inflammatory mediators. We evaluated the laboratory profile
      of coagulations and fibrinolysis in the serum of 148 patients with CAP without
      effusion, 50 with UCPPE and 44 with CPPE. We determined the test of the
      coagulation cascade which measures the time elapsed from the activation of the
      coagulation cascade at different points to the fibrin generation. As a
      consequence, there is an activation of the fibrinolytic system with the increased
      D-dimer levels measured in the plasma in the three groups. The patients were with
      mean age +/- SD (53,82 +/- 17,5) min - max 18-93 years. A significantly higher
      number of thrombocytes was in the group with CPPE with median 412 * 109/L (rank
      323-513 * 109/L). The extended activation of the prothrombin time (aPTT) was
      significantly higher in the same group of patients with median of 32 sec. (rank
      30-35 sec). The mean D-dimer plasma level was 3266,5 +/- 1292,3 ng/ml in patients
      with CPPE, in CAP without effusion 1646,6 +/- 1204 ng/ml and in UCPPE 1422,9 +/-
      970 ng/ml. The coagulations system and the fibrinolysis play important role in
      the development and pathophysiology of CAP and the parapneumonic effusions.

PMID- 27883328
TI  - Factors Associated with Lethal Outcome in Patients with Severe Form of Influenza.
AB  - INTRODUCTION: Clinical manifestations of influenza range from relatively mild and
      self-limiting respiratory infections to severe clinical manifestations with
      significant morbidity and mortality. The awareness of predictive indicators for
      the lethal outcome of influenza is of particular significance in making timely
      and exact decision for adequate treatment. The aim of this study was to identify
      the factors in patients with a severe form of influenza, resulting in lethal
      outcome. MATERIALS AND METHODS: The investigation was a prospective group
      comparison conducted at the University Clinic for Infectious Diseases in Skopje,
      R. Macedonia in the period from January 01, 2012 to January 01, 2015. The study
      included adult patients with a severe form of influenza who were further
      categorized into a group of either survived patients or a group of deceased
      patients. Demographic, clinical and biochemical data were noted in all patients
      included in the study on admission. The variables of the univariate analysis that
      showed a significant difference in terms of the outcome were used for creating
      multivariate logistic and regression analysis of the outcome as dependent
      factors. The independent predictors for lethal outcome in severe cases of
      influenza were identified by using logistic regression. RESULTS: The study
      included 87 patients with a severe form of clinical and laboratory confirmed
      influenza. The patients were divided in two groups: survived (n = 75) and
      deceased (n = 75). The overall mortality was 13.79%. Multivariate analysis
      conducted on admission to hospital identified cardiovascular comorbid diseases (p
      = 0.014), urea values higher than 8.3 U/L (p = 0.045) and SAPS score (p = 0.048)
      as independent predictors of the outcome in patients with severe form of
      influenza. Influenza patients with cardiovascular diseases had 2.024 times
      greater risk of death from influenza in comparison to the patients having
      influenza without history of such a disease (OR = 2.024 95% CI 1.842-17.337).
      Patients with serum urea values higher than 8.3 U/L had 1.89 times higher chance
      of death compared to patients with normal values (OR = 1.89 95% CI 1.091-11.432).
      The increase of the SAPS score in one point increased the chance of death in
      patients with influenza by 1.2% (OR = 1.12 95% CI 1.01-2.976). The ROC analysis
      indicated that cardiovascular diseases, increased urea values and SAPS score in
      combination act as a good prognostic model for the fatal outcome. The global
      authenticity of this predictive model to foresee lethal outcome amounts to 80%,
      sensitivity being 82%, and specificity 70%. CONCLUSION: Cardiovascular diseases,
      increased values of urea over 8.3 mmol/l and SAPS score are independent
      predictive indicators for lethal outcome in severe influenza. Early
      identification of the outcome predictors in patients with severe influenza will
      allow implementation of adequate medical treatment and will contribute to
      decreasing of mortality in patients with severe form of influenza.

PMID- 27883329
TI  - How to Recognize and Avoid Potential, Possible, or Probable Predatory Open-Access
      Publishers, Standalone, and Hijacked Journals.
AB  - INTRODUCTION AND AIM: The Internet has enabled an easy method to search through
      the vast majority of publications and has improved the impact of scholarly
      journals. However, it can also pose threats to the quality of published articles.
      New publishers and journals have emerged so-called open-access potential,
      possible, or probable predatory publishers and journals, and so-called hijacked
      journals. It was our aim to increase the awareness and warn scholars, especially
      young researchers, how to recognize these journals and how to avoid submission of
      their papers to these journals. METHODS: Review and critical analysis of the
      relevant published literature, Internet sources and personal experience,
      thoughts, and observations of the authors. RESULTS: The web blog of Jeffrey
      Beall, University of Colorado, was greatly consulted. Jeffrey Beall is a Denver
      academic librarian who regularly maintains two lists: the first one, of
      potential, possible, or probable predatory publishers and the second one, of
      potential, possible, or probable predatory standalone journals. Aspects related
      to this topic presented by other authors have been discussed as well. CONCLUSION:
      Academics should bear in mind how to differentiate between trustworthy and
      reliable journals and predatory ones, considering: publication ethics, peer
      review process, international academic standards, indexing and abstracting,
      preservation in digital repositories, metrics, sustainability, etc.

PMID- 27883330
TI  - Effects of 17beta-estradiol (E2) on aqueous organisms and its treatment problem:
      a review.
AB  - Natural estrogens, estrone (E1), 17beta-estradiol (E2) and estriol (E3) are
      endocrine disrupting chemicals (EDCs) that are discharged consistently and
      directly into surface waters with wastewater treatment plants (WWPTs) effluents,
      disposal sludges and in storm-water runoff. The most common and highest potential
      natural estrogen that causes estrogen activity in wastewater influent is E2. This
      review describes and attempts to summarize the main problems involved in the
      removal of E2 from WWTP by traditional processes, which fundamentally rely on
      activated sludge and provide an insufficient treatment for E2, as well as
      advanced oxidation processes (AOPs) that are applied in tertiary section
      treatment works. Biological processes affect and play an important role in the
      degradation of E2. However, some investigations have reported that operations
      that rely on high retention times have low efficiencies. Although advanced
      treatment technologies are available, their cost and operational considerations
      do not make them sustainable solutions. Therefore, E2 is still being released
      into aqueous areas, as shown in this study that investigates results from
      different countries. E2 is present on the watch list of substances in the Water
      Framework Directive (WFD) of the European Union since 2013 and the minimum
      acceptable concentration of it is 0.4 ng/L.

PMID- 27883331
TI  - Effects of altered RTN3 expression on BACE1 activity and Alzheimer's neuritic
      plaques.
AB  - Reticulon 3 (RTN3), which is a member of the reticulon family of proteins, has a
      biochemical function of shaping tubular endoplasmic reticulum. RTN3 has also been
      found to interact with beta-site amyloid precursor protein cleaving enzyme 1
      (BACE1), which initiates the generation of beta-amyloid peptides (Abeta) from
      amyloid precursor protein. Abeta is the major proteinaceous component in neuritic
      plaques, which constitute one of the major pathological features in brains of
      Alzheimer's disease (AD) patients. Mice deficient in or overexpressing RTN3 have
      altered amyloid deposition through effects on BACE1 expression and activity. In
      this review, we will summarize the current findings concerning the role of RTN3
      in AD pathogenesis and demonstrate that RTN3 protein levels act as age-dependent
      modulators of BACE1 activity and Abeta deposition during the pathogenic
      progression of AD.

PMID- 27883332
TI  - Effect of signal acquisition method on the fetal heart rate analysis with phase
      rectified signal averaging.
AB  - Phase rectified signal averaging (PRSA) is increasingly used for fetal heart rate
      (FHR) monitoring, both with traces acquired with external Doppler
      cardiotocography (D-FHR), and with transabdominal fetal electrocardiography (ta
      FHR). However, it is unclear to what extend the acquisition method influences the
      PRSA analysis, whether results from using one acquisition method are comparable
      to those based on FHR acquired by the other method, and if not, which should be
      the preferred method. To address these questions, we applied PRSA analysis to 28
      antepartum synchronous recordings of the FHR using simultaneously D-FHR and ta
      FHR. The data included late-onset intrauterine growth restricted (IUGR) fetuses
      (n  =  20) and non-IUGR fetuses (n  =  8), all of them at gestation  ?34 weeks.
      PRSA analysis depends on two parameters intrinsic to the algorithm, T and S. We
      analyzed the data using parameters that included all values adopted by other
      researchers previously (derived from a literature search in PubMed and Google
      Scholar). T and S were adjusted for the difference in acquisition techniques. We
      found that the correlation between PRSA analysis based on D-FHR and ta-FHR
      decreased with decreasing values of the PRSA parameters T and S. Therefore, the
      acquisition technique affects PRSA values for high resolution PRSA (low values of
      T and S). In conclusion, for low resolution PRSA, the results from both
      acquisition methods are comparable. Because ta-FHR signals provide beat to beat
      data and thus capture more subtle differences in the heart rate variation than D
      FHR signals (pre-processed by commercial monitors), we assumed that ta-FHR may
      provide potentially valuable extra information compared to D-FHR. However, no
      parameter settings or acquisition method seemed to have a diagnostic value for
      identifying the late-onset IUGR babies in our dataset.

PMID- 27883333
TI  - Design of a simple coronary impedance simulator for the in vitro study of the
      complex coronary hemodynamics.
AB  - Several novel approaches were recently developed to treat aortic root
      pathologies. The alteration induced by some of these approaches to the
      biomechanics of the aortic root could possibly affect the coronary perfusion,
      compromising the procedural outcome. In this scenario, the need to replicate in
      vitro the coronary flow pattern in physiological and pathological conditions is
      becoming crucial for the functional assessment of novel devices and techniques.
      This article describes the design of an easy-to-use, left-and-right coronary
      impedance simulator, coupled with native aortic roots for in vitro pulsatile
      tests. Experiments were performed in order to assess the performances of the
      coronary impedance simulator when coupled with healthy aortic valves (cardiac
      output: 3.8  +/-  0.26 l min-1; mean systemic pressure: 95  +/-  1.3 mmHg; mean
      coronary flow rate: 272  +/-  13.4 ml min-1) or with regurgitant valves (cardiac
      output: 1.9  +/-  0.24 l min-1; mean systemic pressure of 45  +/-  3.3 mmHg; mean
      coronary flow rate:149  +/-  21.9 ml min-1). The acute systemic response to valve
      regurgitation was also replicated, with increased beat rate and afterload, aimed
      at restoring the systemic pressure (cardiac output: 2.5  +/-  0.23 l min-1; mean
      systemic pressure of 109  +/-  6.1 mmHg; mean coronary flow rate: 262  +/-  35.5
      ml min-1). In the test conditions, the system was able to replicate in vitro the
      main determinants of the coronary circulation with physiological left/right
      coronary flow rate repartition, and a realistic interaction between coronary and
      systemic hemodynamics. The coronary simulator appears to be a suitable platform
      to study and optimize the interactions between novel approaches to aortic valve
      pathology and the coronary perfusion.

PMID- 27883334
TI  - Effect of cation dopants in zirconia on interfacial properties in nickel/zirconia
      systems: an atomistic modeling study.
AB  - Cation doping is often used to stabilize the cubic or tetragonal phase of
      zirconia for enhanced thermomechanical and electrochemical properties. In the
      present paper we report a combined density functional theory (DFT) and molecular
      dynamics study of the effect of Sc, Y, and Ce dopants on properties of
      Ni/[Formula: see text] interfaces and nickel sintering. First, we develop an MD
      model that is based on DFT data for various nickel/zirconia interfaces. Then, we
      employ the model to simulate Ni nanoparticles coalescing on a zirconia surface.
      The results show the possibility of particle migration by means of fast sliding
      over the surface when the work of separation is small (<[Formula: see text]). The
      sliding observed for the O-terminated Ni(1 1 1)/[Formula: see text](1 1 1)
      interface is not affected by dopants in zirconia because the work of separation
      of the doped interface stays small. The most pronounced effect of the dopants is
      observed for the Zr-terminated Ni(1 1 1)/[Formula: see text](1 1 1) interface,
      which possesses a large work of separation ([Formula: see text]) and thus
      restricts the sliding mechanism of Ni nanoparticle migration. DFT calculations
      for the interface revealed that dopants with a smaller covalent radius result in
      a larger energy barriers for Ni diffusion. We analyze this effect and discuss how
      it can be used to suppress nickel sintering by using the dopant selection.

PMID- 27883343
TI  - Interhemispheric connectivity estimated from EEG time-correlation analysis in
      preterm infants with normal follow-up at age of five.
AB  - Brain connectivity is associated with axonal connections between brain
      structures. Our goal was to quantify the interhemispheric neuronal connectivity
      in healthy preterm infants by automated quantitative EEG time-correlation
      analysis. As with advancing postmenstrual age (PMA, gestational age  +  postnatal
      age) the neuronal connectivity between left and right hemisphere increases, we
      expect to observe changes in EEG time-correlation with age. Thirty-six
      appropriate-for-gestational age preterm infants (PMA between 27-37 weeks) and
      normal neurodevelopmental follow-up at 5 years of age were included. Of these, 22
      infants underwent 3-8 repeated EEG recordings at weekly intervals. The reduced 10
      20 EEG electrode system for newborns was used with five sets of bipolar channels:
      central-temporal, frontal polar-temporal, frontal polar-central, temporal
      occipital and central-occipital. We performed EEG time-correlation analysis
      between homologous channels of the brain hemispheres to identify interhemispheric
      similarity in EEG signal shape. For each 8 s epoch of the EEG the time
      correlation values and the corresponding lag times were calculated for homologous
      channels on both hemispheres. In all channels, the median correlation value
      decreased significantly (between  -40% and  -60% decrease) from 27 to 37 weeks
      PMA, for gestational maturation. For the postnatal maturation only the central
      temporal channel showed a significantly decreasing trend. In contrast, the median
      lag time showed no uniform change with PMA. The decreasing median correlation
      values in all homologous channels indicate a decrease in similarity in signal
      shape with advancing PMA. This finding may reflect greater functional
      differentiation of cortical areas in the developing preterm brain and may be
      explained by the increase of complex neural networks with excitatory and
      inhibitory circuitries.

PMID- 27883344
TI  - Analysis of non-EEG evidence for preparatory activity in the human brain: pre
      contraction impedance changes in skeletal muscles.
AB  - Precontraction impedance changes (PICs) are known to occur during isometric
      contractions of the human forearm finger flexors. Without reliance on
      electroencephalogical data these are construed as evidence for the construction
      of a 'template of instructions' in the brain for muscle contractions to be
      performed once a 'go' instruction is received, as widely expected from EEG
      measurements A model is proposed to explain earlier impedance results, based on a
      PIC-associated time-dependent inhibitory constraint and a modified role for the
      'go' command. A principal result is that (for appropriate choice of parameters)
      the time difference between occurrence of a PIC and the onset of force generation
      can be independent of the timing of the 'go' command, as has in fact been
      reported earlier. Independent of the detailed model, it is argued that there is
      no reproducible relationship between the time of occurrence of a PIC and the
      emergence of force, even for repeat tests on the same subject. However, we
      propose that results for a wide range of circumstances are nevertheless governed
      by a common probability distribution, based on data for 1200 PICs in a cohort of
      11 healthy young subjects.

PMID- 27883346
TI  - [Effect of physical activity on longevity].
AB  - Multiple population studies have reported a positive correlation between higher
      levels of physical activity (PA) and longer lifespan. It has been generally
      accepted that it occurs due to PA having a direct effect on longevity. However,
      this idea is negated by experiments on animal models and an observational study
      on a twin cohort published recently by Karvinen et al. This unique study includes
      a pairwise comparison of monozygotic twins discordant for PA, therefore
      eliminating any influence of genetic factors on both mortality and tendency to
      take up exercise. The intriguing lack of differences in lifespan in such pairs
      implies that PA is not an important life prolonging factor. This discovery casts
      doubt on the validity of PA recommendations found in numerous medical guidelines.
      Nevertheless, the mentioned results apply only to the plain PA - longevity
      relation. They do not consider health benefits of PA, for which solid evidence
      exists. In particular, PA clearly reduces the risk of obesity-related diseases.
      This may indirectly yet significantly affect the length and quality of life, even
      if the direct relationship between PA and lifespan will be proven false in
      further research.

PMID- 27883345
TI  - Filtering for productive activity changes outcomes in step-based monitoring among
      children.
AB  - Wearable activity monitors are increasingly prevalent in health research, but
      there is as yet no data-driven study of artefact removal in datasets collected
      from typically developing children across childhood. Here, stride count data were
      collected via a commercially available activity monitor (StepWatch), which
      employs an internal filter for sub-threshold accelerations, but does not post
      process supra-threshold activity data. We observed 428 typically-developing
      children, ages 2-15, wearing the StepWatch for 5 consecutive days. We developed a
      minimum per-minute stride-count below which the data outputted from the StepWatch
      could be considered 'idle' and not 'productive'. We found that a threshold stride
      count of 10 steps per minute captured 90% of samples in a weighted average among
      isolated non-zero stride-count samples offset by inactivity. This threshold did
      not vary by age, gender, or by an age-gender interaction. Filtering the activity
      data according to this threshold reduced overall stride count by 8-10% by age
      group, from 8177  +/-  2659 to 7432  +/-  2641 strides per day. The impact on
      number of bouts per day decreased from an overall average of 79.3  +/-  17.2 to
      72.7  +/-  12.1; this effect varied by age group. This study delivers the first
      data-driven estimate of a minimum activity threshold in step- or stride units
      that may extend to other studies. We conclude that the impact of production-idle
      filtering on activity data is substantial and suggests a possible impetus for re
      contextualizing extant studies and guidelines reported without such filtering.

PMID- 27883347
TI  - [Adalimumab as induction therapy for Crohn's disease - one center study].
AB  - : Adalimumab is a subcutaneously administered recombinant fully human monoclonal
      antibody targeting tumor necrosis factor alpha. It has been approved for use in
      Poland to treat patients with Crohn's disease under the program of Polish
      National Health Found since 2010. AIM: The aim of this study was to evaluate the
      efficacy of adalimumab monotherapy for inducing clinical remission in patients
      with active Crohn's disease . The primary outcome assessment was the reduction in
      score to 150 or below on the Crohn's Disease Activity Index (CDAI) at 12 weeks
      and the secondary one was the reduction in DeltaCDAI of at least 100 points.
      MATERIALS AND METHODS: From January 2011 to December 2015 we treated 68 patients
      with active Crohn's disease (mean CDAI score 359). All the patients came from
      region of Silesia, an area with the same environment conditions. The patients
      were given adalimumab (Humira, AbbVie) subcutaneously at a dose of 160 mg at week
      0, 80 mg at week 4 and 40 mg every two weeks thereafter. RESULTS: Twenty eight
      patients (41%) had a clinical remission at week 12 (CDAI <=150) and 33 patients
      (49%) had a DeltaCDAI response. During the 12-week of induction therapy infection
      with Clostridium difficile occurred in 4 patients and one patient died of a
      severe CMV infection. CONCLUSIONS: Adalimumab is effective as induction therapy
      for patients with moderate-to-severe Crohn's disease, however in individual cases
      serious infections including CMV infection can occur. A potential predictive
      factors for response can be female gender, non-smoking status and high CRP level
      at baseline.

PMID- 27883348
TI  - [Cognitive emotion regulation of patients qualified for implantation of heart
      rhythm control device].
AB  - : The aim of the artificial heart stimulation is not only saving lives, but also
      improvement of the quality of life of patients with cardiac arrhythmias. One of
      the key dimensions of quality of life is psychological functioning. Until now,
      little research assess this dimension in patients before the implantation of the
      heart rhythm control device. AIM: The aim of the study was to assess the severity
      of depression and anxiety and the frequency of the used cognitive emotion
      regulation strategies and to examine the relationship between them. MATERIALS AND
      METHODS: The study group consisted of 60 people qualified for pacemaker
      implantation (42 PM patients and 18 ICD): 15 women and 45 men ranging in age from
      43 to 85. To assess cognitive emotion regulation strategies Cognitive Emotion
      Regulation Questionnaire was used, and to assess the severity of depression and
      anxiety - Mood Assessment Questionnaire. RESULTS: Patients with PM more often
      than patients with ICD use the strategy of Positive Reappraisal (U = 231.50, p =
      0.045). There were no statistically significant differences in the frequency of
      use of other strategies and severity of depression and anxiety. In PM patients
      there are negative correlations between the severity of depression and anxiety
      and the use of Acceptance ( tau = -0.380), a Positive Reappraisal ( tau = 
      0.278), Positive Refocusing ( tau = -0.366) and between the level of anxiety and
      Putting into Perspective ( tau = -0.402). In ICD patients there was a positive
      relationship between anxiety and Cathastrophizing ( tau = 0.324). CONCLUSIONS:
      The severity of depression and anxiety, and emotion regulation strategies in
      patients qualified for PM implantation in comparison with patients qualified for
      ICD implantation are similar. Both groups of patients show a good adaptation of
      the psychological.

PMID- 27883349
TI  - [The education influence on effects of rehabilitation in patients after stroke].
AB  - : Patients after stroke face a new situation where some educational and
      pedagogical actions should be reinitiated. Stroke often causes a break away from
      the previous lifestyle. It the acute phase it excludes the possibility of
      employment or performance of household duties that were carried out before or
      indulging in previously preferred ways of spending free time. Patients often
      abandon the habits that they developed before stroke, inclusive of hygienic
      habits. Therefore, it is an important objective of rehabilitation to reinstate in
      stroke patients behaviours characteristic of their peers, which would mark the
      beginning of their own care for health. The pedagogic and educational activities
      should lead to a transformation in the patient. This could be one of the factors
      in facilitating the patient's return to previous forms of activity. AIM: The aim
      of this study was to analyze progress in patient's rehabilitation and
      satisfaction, to assess impact of health education on higher satisfaction and
      better knowledge in stroke patients as well as on their recovery. Another aim was
      to assess the factors that maximize the patients' chances of returning to the
      labor market. MATERIALS AND METHODS: The study involved 30 patients after stroke,
      8 women and 22 men, over 40 years of age, who underwent either early or late
      rehabilitation, the type of which affected the time of treatment. The minimal
      duration of the patient's stay was 21 days, in which time an individually
      tailored way of education, rehabilitation, treatment and care was implemented.
      The study used a questionnaire and the Bartel and the Rankin scales. The subject
      of the analysis consisted of 22 questions that were based on hypotheses. They
      assessed the facts, the sources of information, knowledge and subjective feelings
      of the patients concerning the education carried out by the rehabilitation team
      and its impact on the patients' rehabilitation. RESULTS: A highly significant
      (p<0,01) improvement to patients' health and an increase in their knowledge were
      observed in the rehabilitation. CONCLUSIONS: During the rehabilitation patients
      gained a significant improvement to their health, which resulted in more
      independence in daily living. The implemented health education has an effect on
      the scope of the patients' knowledge during and after rehabilitation, which
      translates into a higher satisfaction from the patient's education. The acquired
      knowledge and skills increase the chances of the patient to return to activities
      and participation in social life at a satisfactory level. The members of the
      rehabilitation team, especially the physicians, play an important role in health
      education of patients.

PMID- 27883350
TI  - Loeffler endocarditis in young woman - a case report.
AB  - Loeffler endocarditis is a rare acquired endocardial and myocardial disease
      characterized by a sharp decrease in the compliance of either or both ventricles
      with an acute diastolic dysfunction and massive mural thrombosis. This disease is
      presented in the classification of cardiomyopathies and is a variant of
      restrictive cardiomyopathy. Today Loeffler endocarditis is considered as a
      manifestation of hypereosinophilic syndrome with predominant heart involvement.
      The life-time diagnosis of myocardial injury due to eosinophilic infiltration is
      rare, or it is diagnosed at the stage of necrotizing endomyocarditis, when the
      treatment is no longer effective. A number of issues regarding the individual
      aspects of the pathogenesis of hypereosinophilic syndrome and Loeffler
      endocarditis are still not fully understood, as well as the long-term prospects
      for the use of drugs for the treatment of hypereosinophilic syndrome, especially
      in young and middle-aged persons. Loeffler endocarditis can be suspected in the
      presence of hypereosinophilia on the background of causeless (unexplainable)
      hypertrophy of the left ventricle or both ventricles. The article includes a case
      of the life-time diagnosis of this disease in a young woman with the
      retrospective analysis of the early stages of the disease, echocardiographic and
      radiologic imaging at the advanced stage of the disease and quite successful
      treatment option for this disease.

PMID- 27883351
TI  - [Rivaroxaban-resistant right ventricular thrombus, successfully treated with
      vitamin K antagonist in a patient with dilated cardiomyopathy].
AB  - : Rivaroxaban, a selective inhibitor of active factor X belongs to the group of
      direct-acting oral anticoagulants (DOAC), more and more often replacing vitamin K
      antagonists (VKA) in venous thromboembolic disease and nonvalvular atrial
      fibrillation. Attempts are also being made to use DOAC to treat locally formed
      intracardiac thrombi, mainly in the left atrium and its appendage, in atrial
      fibrillation and in heart failure. Rarely diagnosed local right ventricular
      thrombus (RVT) may be a complication of dilated cardiomyopathy (DCM). CASE
      REPORT: The authors present a case of a 40-year-old male with DCM and RVT located
      in the apex, which was imaged in echocardiography, magnetic resonance and
      multislice computed tomography. During treatment with rivaroksaban (2x15 mg: 4
      weeks; 1x20 mg: 4 months) diminishing of RVT was not observed. After 2 months of
      VKA use complete resolution of RVT was noted. The case presented is probably the
      first described RVT treated with rivaroxaban. The authors conclude that in some
      cases, anticoagulation with VKA may be more effective than DOAC in intracardiac
      thrombi therapy, especially when it is meticulously monitored. Overlapping effect
      on RVT due to anticoagulants use with a different mechanism of action cannot be
      excluded.

PMID- 27883352
TI  - [Long-term prognosis in patients with vasovagal syncope after pacemaker
      implantation].
AB  - Patients with syncope, without presence of a structural or primary electrical
      disease, have a very good prognosis. On the other hand, recurring syncope has a
      negative impact on quality of life and involves a real risk of physical injuries.
      Vasovagal syncope usually requires no medical therapy and the most commonly
      recommended instruction include avoidance of fainting triggers, exercise that
      mainly provoke leg muscles tension, increase salt consumption and drink indicated
      amount of fluids. In the case cardioinhibitory type of vasovagal syncope the
      pacemaker implantation can consider. Unfortunately, not all patients benefit from
      this treatment. Medical society clearly highlights that proper qualification of
      VVS patients is the most important factor for cardiostimulator implantation. This
      article aims to summarize the most important research and guidelines concerning
      cardiac pacing for patients with vasovagal syncope.

PMID- 27883354
TI  - [The impact of the consumption of fiber and milk on the development of colorectal
      carcinoma].
AB  - Colorectal carcinoma (CRC) is a diet-related disease. The high incidence of CRC
      is related to the excessive consumption of certain foods and a westernized
      lifestyle of contemporary societies. Obesity and low physical activity remain
      significant risk factors for CRC development. Molecular pathogenesis of CRC is
      fairly well recognized, which contributes to the formulation of hypotheses and
      conducting research on the participation of nutritional factors in the CRC
      development. This contribution remains diverse and for many food components a
      protective effect on colorectal carcinogenesis has been demonstrated. The aim of
      this review is to present a relationship between consumption of two selected
      components of the diet - fiber and milk - and the development of colorectal
      carcinoma, based on the review of literature.

PMID- 27883353
TI  - [Microscopic colitis - a frequent cause of chronic diarrhea].
AB  - Chronic diarrhea is a very common problem in the general population. It requires
      a physician to differentiate its causes and depending on its etiology referring
      the patient to a hospital for diagnosis and subsequent treatment. One of the
      causes of chronic diarrhea may be microscopic colitis, which is characterized by
      the presence of clinical symptoms without endoscopic or radiological
      abnormalities. Diagnosis is based on a histopathological examination of the colon
      and thus clinical suspicion of the disease is so important for further diagnosis
      and treatment, which is primarily based on the use of topical steroids such as
      budesonide.

PMID- 27883355
TI  - [Patient - doctor relationship from perspective of the Karpman drama triangle].
AB  - Patients' confidence in doctors has been decreased for last years despite
      successes of Polish medicine. It seems to be related to particular conditions of
      patient - doctor relationship and patient's negative emotions may frequently
      burden it from the beginning. They may allow an interpersonal game, the Drama
      Triangle, to appear in the relationship. 3 persons are typically involved in the
      game: a victim, a persecutor and a rescuer. All of them neither feel guilty about
      the situation nor their activities are aimed at solving the crucial problem. It
      maintains continuation of the game. Both patient and doctor are capable to attend
      the game as any of the person mentioned above. Authors of the article think
      frameworks of organization of the health care system should permit doctors not
      only to tackle main disease but also to devote time individually tailored to
      patient's emotional problems.

PMID- 27883357
TI  - Corrigendum.

PMID- 27883359
TI  - The Contributions of Dr. Alfred Gysi.
AB  - This article is a historical overview of Dr. Alfred Gysi's contributions to the
      profession in the areas of denture tooth and articulator design. His
      understanding of occlusion and mandibular movement resulted in denture tooth
      designs and occlusal concepts still in widespread use.

PMID- 27883358
TI  - Negative pressure wound therapy inhibits inflammation and upregulates activating
      transcription factor-3 and downregulates nuclear factor-kappaB in diabetic
      patients with foot ulcerations.
AB  - BACKGROUND: Negative pressure wound therapy (NPWT) is one of the most important
      treatments for diabetic foot, but the underlying mechanisms of its benefits still
      remain elusive. This study aims to evaluate the inflammatory signals involved in
      the effects of negative pressure therapy on diabetic foot ulcers. METHODS: We
      enrolled 22 patients with diabetic foot ulceration, 11 treated with NPWT and the
      other 11 treated with traditional debridement. All patients were treated and
      observed for 1 week. Granulation tissues were harvested and analyzed in both
      groups, and then were histologically and immunohistochemically analyzed. Enzyme
      linked immunosorbent assay, Western blot analysis, and real-time PCR were
      performed to evaluate the expression of interleukin-6 (IL-6), tumor necrosis
      factor alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), nuclear factor
      kappaB (NF-kappaB) p65, Ik B-alpha, and activating transcription factor-3 (ATF
      3). RESULTS: After 7 days of treatment, NPWT could obviously promote diabetic
      wound healing because of the mild inflammation and the dense cell-deposited
      matrix. Meanwhile, NPWT significantly decreased the expression of TNF-alpha, IL
      6, and iNOS (all P < .05). The result of Western blotting and real-time PCR
      indicated that NPWT obviously decreased the level of Ik B-alpha and NF-kappaB
      p65, and increased the level of ATF-3 (all P < .05). CONCLUSION: NPWT exerts an
      anti-inflammatory effect, possibly through the suppression of proinflammatory
      enzymes and cytokines resulting from Ik B-alpha inhibition and ATF-3 activation,
      which may prevent the activation of the NF-kappaB pathway in human diabetic foot
      wounds.

PMID- 27883356
TI  - A human brain microphysiological system derived from induced pluripotent stem
      cells to study neurological diseases and toxicity.
AB  - Human in vitro models of brain neurophysiology are needed to investigate
      molecular and cellular mechanisms associated with neurological disorders and
      neurotoxicity. We have developed a reproducible iPSC-derived human 3D brain
      microphysiological system (BMPS), comprised of differentiated mature neurons and
      glial cells (astrocytes and oligodendrocytes) that reproduce neuronal-glial
      interactions and connectivity. BMPS mature over eight weeks and show the critical
      elements of neuronal function: synaptogenesis and neuron-to-neuron (e.g.,
      spontaneous electric field potentials) and neuronal-glial interactions (e.g.,
      myelination), which mimic the microenvironment of the central nervous system,
      rarely seen in vitro before. The BMPS shows 40% overall myelination after 8 weeks
      of differentiation. Myelin was observed by immunohistochemistry and confirmed by
      confocal microscopy 3D reconstruction and electron microscopy. These findings are
      of particular relevance since myelin is crucial for proper neuronal function and
      development. The ability to assess oligodendroglial function and mechanisms
      associated with myelination in this BMPS model provide an excellent tool for
      future studies of neurological disorders such as multiple sclerosis and other
      demyelinating diseases. The BMPS provides a suitable and reliable model to
      investigate neuron-neuroglia function as well as pathogenic mechanisms in
      neurotoxicology.

PMID- 27883360
TI  - Bigger and Brighter Fluorenes: Facile pi-Expansion, Brilliant Emission and
      Sensing of Nitroaromatics.
AB  - pi-Expanded butterfly-like 2D fluorenes and 3D spirobifluorenes 1-5 were
      synthesized via a DDQ-mediated oxidative cyclization strategy with a high
      regioselectivity. Through structural modification via pi-expansion, it was
      possible to achieve near-ultraviolet absorption, bright-blue emission, very high
      near-unity fluorescence quantum yields in solution as well as in film states, and
      deep-lying HOMO energy levels with excellent thermal stabilities. Furthermore,
      these electron-rich compounds displayed a notable behavior towards sensing of
      nitroaromatic explosives, such as picric acid, up to a detection limit of 0.2
      ppb.

PMID- 27883362
TI  - A risk factor-based model for upper aerodigestive tract cancers in India:
      predicting and validating the receiver operating characteristic curve.
AB  - BACKGROUND: A study was conducted to develop and validate a screening model using
      risk scores to identify individuals at high risk for developing upper
      aerodigestive tract (UADT) cancers in an Indian population. METHODS: A hospital
      based case-control study (n = 480) was conducted in Pune, India. We assessed risk
      factors for UADT cancers by administering a questionnaire through face-to-face
      interviews. We developed a risk factor model based on the statistically
      significant risk factors in multiple logistic regression. A total, single risk
      score was calculated per individual based on the adjusted odds ratio for each of
      their risk factors. Standard receiver operator characteristic curve was plotted
      for the total score and the presence of UADT cancers. The stratification ability
      of the model was determined using the c-statistic. The optimal criterion value
      was determined at the point on curve at which the Youden's index was maximal.
      Confidence intervals were calculated by bootstrapping. RESULTS: Total risk score
      for each individual ranged from 0 to 26. Area under the receiver operating
      characteristic curve (95.8; P < 0.001) suggests strong predictive ability. A risk
      score criterion value of <=10 produced optimal sensitivity (93.5%), specificity
      (71.1%), false-positive rate (28.8%), false-negative rate (6.4%), positive
      predictive value (74.8%), and negative predictive value (96.6%). CONCLUSION: This
      risk factor-based model has the potential of satisfactorily screening and
      detection of UADT cancers at its early stage in a high-risk population like
      India. The identified at-risk individuals can then be targeted for clinical
      examination and for focused preventive/treatment measures at the hospital.

PMID- 27883361
TI  - Adaptation to divergent larval diets in the medfly, Ceratitis capitata.
AB  - Variation in diet can influence the timing of major life-history events and can
      drive population diversification and ultimately speciation. Proximate responses
      of life histories to diet have been well studied. However, there are scant
      experimental data on how organisms adapt to divergent diets over the longer term.
      We focused on this omission by testing the responses of a global pest, the
      Mediterranean fruitfly, to divergent selection on larval diets of different
      nutritional profiles. Tests conducted before and after 30 generations of
      nutritional selection revealed a complex interplay between the effects of novel
      larval dietary conditions on both plastic and evolved responses. There were
      proximate-only responses to the larval diet in adult male courtship and the
      frequency of copulation. Males on higher calorie larval diets consistently
      engaged in more bouts of energetic courtship. In contrast, following selection,
      larval development time, and egg to adult survival showed evidence of evolved
      divergence between diet regimes. Adult body size showed evidence for adaptation,
      with flies being significantly heavier when reared on their "own" diet. The
      results show the multifaceted responses of individuals to dietary selection and
      are important in understanding the extreme generalism exhibited by the medfly.

PMID- 27883364
TI  - Determination of S-methyl-L-methionine (SMM) from Brassicaceae Family Vegetables
      and Characterization of the Intestinal Transport of SMM by Caco-2 Cells.
AB  - The objectives of the current study were to determine S-methyl-L-methionine (SMM)
      from various Brassicaceae family vegetables by using validated analytical method
      and to characterize the intestinal transport mechanism of SMM by the Caco-2
      cells. The SMM is well known to provide therapeutic activity in peptic ulcers.
      The amount of SMM from various Brassicaceae family vegetables ranged from 89.08
      +/- 1.68 MUg/g to 535.98 +/- 4.85 MUg/g of dry weight by using validated ultra
      performance liquid chromatography-electrospray ionization-mass spectrometry
      method. For elucidating intestinal transport mechanism, the cells were incubated
      with or without transport inhibitors, energy source, or a metabolic inhibitor.
      Phloridzin and verapamil as inhibitors of sodium glucose transport protein
      (SGLT1) and P-glycoprotein, respectively, were not responsible for cellular
      uptake of SMM. Glucose and sodium azide were not affected by the cellular
      accumulation of SMM. The efflux ratio of SMM was 0.26, implying that it is not
      effluxed through Caco-2 cells. The apparent coefficient permeability (Papp ) of
      SMM was 4.69 * 10-5 cm/s, indicating that it will show good oral absorption in in
      vivo.

PMID- 27883363
TI  - Sexual selection shapes development and maturation rates in Drosophila.
AB  - Explanations for the evolution of delayed maturity usually invoke trade-offs
      mediated by growth, but processes of reproductive maturation continue long after
      growth has ceased. Here, we tested whether sexual selection shapes the rate of
      posteclosion maturation in the fruit fly Drosophila melanogaster. We found that
      populations maintained for more than 100 generations under a short generation
      time and polygamous mating system evolved faster posteclosion maturation and
      faster egg-to-adult development of males, when compared to populations kept under
      short generations and randomized monogamy that eliminated sexual selection. An
      independent assay demonstrated that more mature males have higher fitness under
      polygamy, but this advantage disappears under monogamy. In contrast, for females
      greater maturity was equally advantageous under polygamy and monogamy.
      Furthermore, monogamous populations evolved faster development and maturation of
      females relative to polygamous populations, with no detectable trade-offs with
      adult size or egg-to-adult survival. These results suggest that a major aspect of
      male maturation involves developing traits that increase success in sexual
      competition, whereas female maturation is not limited by investment in traits
      involved in mate choice or defense against male antagonism. Moreover, rates of
      juvenile development and adult maturation can readily evolve in opposite
      directions in the two sexes, possibly implicating polymorphisms with sexually
      antagonistic pleiotropy.

PMID- 27883365
TI  - Educational interventions for the management of cancer-related fatigue in adults.
AB  - BACKGROUND: Cancer-related fatigue is reported as the most common and distressing
      symptom experienced by patients with cancer. It can exacerbate the experience of
      other symptoms, negatively affect mood, interfere with the ability to carry out
      everyday activities, and negatively impact on quality of life. Educational
      interventions may help people to manage this fatigue or to cope with this
      symptom, and reduce its overall burden. Despite the importance of education for
      managing cancer-related fatigue there are currently no systematic reviews
      examining this approach. OBJECTIVES: To determine the effectiveness of
      educational interventions for managing cancer-related fatigue in adults. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), and MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, OTseeker and PEDro up to
      1st November 2016. We also searched trials registries. SELECTION CRITERIA: We
      included randomised controlled trials (RCTs) of educational interventions focused
      on cancer-related fatigue where fatigue was a primary outcome. Studies must have
      aimed to evaluate the effect of educational interventions designed specifically
      to manage cancer-related fatigue, or to evaluate educational interventions
      targeting a constellation of physical symptoms or quality of life where fatigue
      was the primary focus. The studies could have compared educational interventions
      with no intervention or wait list controls, usual care or attention controls, or
      an alternative intervention for cancer-related fatigue in adults with any type of
      cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently screened
      studies for inclusion and extracted data. We resolved differences in opinion by
      discussion. Trial authors were contacted for additional information. A third
      independent person checked the data extraction. The main outcome considered in
      this review was cancer-related fatigue. We assessed the evidence using GRADE and
      created a 'Summary of Findings' table. MAIN RESULTS: We included 14 RCTs with
      2213 participants across different cancer diagnoses. Four studies used only
      'information-giving' educational strategies, whereas the remainder used mainly
      information-giving strategies coupled with some problem-solving, reinforcement,
      or support techniques. Interventions differed in delivery including: mode of
      delivery (face to face, web-based, audiotape, telephone); group or individual
      interventions; number of sessions provided (ranging from 2 to 12 sessions); and
      timing of intervention in relation to completion of cancer treatment (during or
      after completion). Most trials compared educational interventions to usual care
      and meta-analyses compared educational interventions to usual care or attention
      controls. Methodological issues that increased the risk of bias were evident
      including lack of blinding of outcome assessors, unclear allocation concealment
      in over half of the studies, and generally small sample sizes. Using the GRADE
      approach, we rated the quality of evidence as very low to moderate, downgraded
      mainly due to high risk of bias, unexplained heterogeneity, and imprecision.There
      was moderate quality evidence of a small reduction in fatigue intensity from a
      meta-analyses of eight studies (1524 participants; standardised mean difference
      (SMD) -0.28, 95% confidence interval (CI) -0.52 to -0.04) comparing educational
      interventions with usual care or attention control. We found low quality evidence
      from twelve studies (1711 participants) that educational interventions had a
      small effect on general/overall fatigue (SMD -0.27, 95% CI -0.51 to -0.04)
      compared to usual care or attention control. There was low quality evidence from
      three studies (622 participants) of a moderate size effect of educational
      interventions for reducing fatigue distress (SMD -0.57, 95% CI -1.09 to -0.05)
      compared to usual care, and this could be considered clinically significant.
      Pooled data from four studies (439 participants) found a small reduction in
      fatigue interference with daily life (SMD -0.35, 95% CI -0.54 to -0.16; moderate
      quality evidence). No clear effects on fatigue were found related to type of
      cancer treatment or timing of intervention in relation to completion of cancer
      treatment, and there were insufficient data available to determine the effect of
      educational interventions on fatigue by stage of disease, tumour type or group
      versus individual intervention.Three studies (571 participants) provided low
      quality evidence for a reduction in anxiety in favour of the intervention group
      (mean difference (MD) -1.47, 95% CI -2.76 to -0.18) which, for some, would be
      considered clinically significant. Two additional studies not included in the
      meta-analysis also reported statistically significant improvements in anxiety in
      favour of the educational intervention, whereas a third study did not. Compared
      with usual care or attention control, educational interventions showed no
      significant reduction in depressive symptoms (four studies, 881 participants, SMD
      -0.12, 95% CI -0.47 to 0.23; very low quality evidence). Three additional trials
      not included in the meta-analysis found no between-group differences in the
      symptoms of depression. No between-group difference was evident in the capacity
      for activities of daily living or physical function when comparing educational
      interventions with usual care (4 studies, 773 participants, SMD 0.33, 95% CI 
      0.10 to 0.75) and the quality of evidence was low. Pooled evidence of low quality
      from two of three studies examining the effect of educational interventions
      compared to usual care found an improvement in global quality of life on a 0-100
      scale (MD 11.47, 95% CI 1.29 to 21.65), which would be considered clinically
      significant for some.No adverse events were reported in any of the studies.
      AUTHORS' CONCLUSIONS: Educational interventions may have a small effect on
      reducing fatigue intensity, fatigue's interference with daily life, and general
      fatigue, and could have a moderate effect on reducing fatigue distress.
      Educational interventions focused on fatigue may also help reduce anxiety and
      improve global quality of life, but it is unclear what effect they might have on
      capacity for activities of daily living or depressive symptoms. Additional
      studies undertaken in the future are likely to impact on our confidence in the
      conclusions.The incorporation of education for the management of fatigue as part
      of routine care appears reasonable. However, given the complex nature of this
      symptom, educational interventions on their own are unlikely to optimally reduce
      fatigue or help people manage its impact, and should be considered in conjunction
      with other interventions. Just how educational interventions are best delivered,
      and their content and timing to maximise outcomes, are issues that require
      further research.

PMID- 27883366
TI  - A Model Practice Template for Hydrotherapy in Labor and Birth.

PMID- 27883368
TI  - Challenges in Research and Practice in Residential Long-Term Care.

PMID- 27883367
TI  - A drop in the circulating concentrations of soluble receptor for advanced
      glycation end products is associated with seroconversion to autoantibody
      positivity but not with subsequent progression to clinical disease in children en
      route to type 1 diabetes.
AB  - BACKGROUND: Advanced glycation end products (AGEs) and their interaction with the
      receptor for AGEs (RAGE) have been studied for their role in the pathogenesis and
      complications of type 1 diabetes. Decreased concentrations of soluble RAGE
      (sRAGE) have been reported in acute autoimmune inflammation. We set out to
      analyze the changes in sRAGE concentration during preclinical diabetes in
      children seroconverting to islet autoantibody positivity. METHODS: We measured
      serum concentrations of sRAGE in 168 children who progressed to clinical disease
      and 43 children who turned positive for at least 2 diabetes-associated
      autoantibodies but remained nondiabetic. We analyzed the sRAGE before
      seroconversion in the first autoantibody-positive sample and annually thereafter
      until the diagnosis of type 1 diabetes or end of follow-up. RESULTS: Both groups
      had similar sRAGE before seroconversion, but subsequently, sRAGE concentrations
      were lower (P < .001) in the progressors. The progressors had significantly
      higher sRAGE concentrations before than after seroconversion (P < .001). The
      nonprogressors did not experience a similar decrease. The sRAGE concentrations
      remained stable after seroconversion in both groups. CONCLUSIONS: These data
      indicate that sRAGE may be involved in the initiation of beta-cell autoimmunity
      but not in the progression from beta-cell autoimmunity to clinical disease.

PMID- 27883369
TI  - Acinetobacter Prosthetic Joint Infection Treated with Debridement and High-Dose
      Tigecycline.
AB  - Prosthesis retention is not recommended for multidrug-resistant Acinetobacter
      prosthetic joint infection due to its high failure rate. Nevertheless, replacing
      the prosthesis implies high morbidity and prolonged hospitalization. Although
      tigecycline is not approved for the treatment of prosthetic joint infection due
      to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude
      prosthesis exchange. Since the area under the curve divided by the minimum
      inhibitory concentration is the best pharmacodynamic predictor of its efficacy,
      we used tigecycline at high dose, in order to optimize its efficacy and achieve
      implant retention in 3 patients who refused prosthesis exchange. All patients
      with prosthetic joint infections treated at our Institution are prospectively
      registered in a database. Three patients with early prosthetic joint infection of
      total hip arthroplasty due to multidrug resistant A. baumannii were treated with
      debridement, antibiotics and implant retention, using a high maintenance dose of
      tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All
      patients signed informed consent for receiving off-label use of tigecycline.
      Tigecycline was well tolerated, allowing its administration at high maintenance
      dose for a median of 40 days (range 30-60). Two patients were then switched to
      minocycline at standard doses for a median of 3.3 months in order to complete
      treatment. Currently, none of the patients showed relapse. Increasing the dose of
      tigecycline could be considered as a means to better attain pharmacodynamic
      targets in patients with severe or difficult-to-treat infections. Tigecycline at
      high maintenance dose might be useful when retention of the implant is attempted
      for treatment for prosthetic joint infections due to multidrug resistant
      Acinetobacter. Although this approach might be promising, off-label use of
      tigecycline should be interpreted cautiously until prospective data are
      available. Tigecycline is probably under-dosed for the treatment of implant and
      biofilm associated infections.

PMID- 27883370
TI  - Epstein-Barr Virus Associated Hemophagocytic Syndrome after Scrub Typhus
      Infection.
AB  - There have been a small number of cases of scrub typhus-associated hemophagocytic
      syndrome (HPS), most of which were treated successfully using adequate
      antibiotics. Here, we report a case of Epstein-Barr virus (EBV)-associated HPS
      after scrub typhus infection that was not improved using antirickettsial
      treatment. A 73-year-old male who had been diagnosed with scrub typhus according
      to an eschar and a positive serology was transferred to our institution because
      of a persistent fever despite 7-day doxycycline therapy. Physical and laboratory
      data showed hepatosplenomegaly, bicytopenia, hyperferritinemia, and
      hypofibrinogenemia. A bone marrow examination (BM) revealed hypercellular marrow
      with hemophagocytosis and histiocyte infiltration. EBV was detected in BM
      aspirates using polymerase chain reaction. After a diagnosis of HPS was made, the
      patient was treated successfully using high-dose steroids.

PMID- 27883371
TI  - Severe Fever with Thrombocytopenia Syndrome Presenting with Hemophagocytic
      Lymphohistiocytosis.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne
      disease caused by the newly discovered SFTS Bunyavirus, and there have been no
      case reports of SFTS patients presenting with hemophagocytic lymphohistiocytosis
      (HLH) in the English literature. We report a case of SFTS presenting with HLH in
      a 73-year-old immunocompetent male farmer. Although the patient had poor
      prognostic factors for SFTS, such as old age and central nervous system symptoms,
      he recovered fully with supportive care.

PMID- 27883372
TI  - A Case of Transverse Myelitis Caused by Varicella Zoster Virus in an
      Immunocompetent Older Patient.
AB  - Varicella zoster virus (VZV) is a human neurotropic alphaherpesvirus that causes
      chickenpox (varicella) in children. VZV reactivation may lead to neurological
      complications, including transverse myelitis. However, transverse myelitis caused
      by VZV reactivation is rare in immunocompetent patients. Herein, we report a case
      of transverse myelitis caused by VZV in an immunocompetent older patient, and
      confirmed this case by polymerase chain reaction. A 79-year-old woman visited our
      service with complaints of weakness in the right lower leg, generalized vesicular
      eruptions, and throbbing pain in the right flank for ten days. Spine MRI showed
      transverse myelitis in the thoracic spine at level T4-T11. The patient was
      treated with acyclovir and her neurological functions improved, except for
      sensory impairment below level T10. For older patients, early and aggressive
      antiviral treatment against VZV may be necessary even though these patients are
      immunocompetent.

PMID- 27883373
TI  - Clinical Impact of Mixed Respiratory Viral Infection in Children with Adenoviral
      Infection.
AB  - BACKGROUND: Although adenovirus (ADV) infection occurs steadily all year round in
      Korea and the identification of respiratory viral coinfections has been
      increasing following the introduction of multiplex real-time polymerase chain
      reaction tests, the clinical impact of viral coinfection in children with ADV
      infection has rarely been reported. MATERIALS AND METHODS: Medical records of
      children diagnosed with ADV infection were retrospectively reviewed. The enrolled
      children were divided into two groups based on the identified respiratory
      viruses: ADV group and coinfection group. Clinical and laboratory parameters were
      compared between the two groups. RESULTS: In total, 105 children (60 males and 45
      females) with a median age of 29 months (range: 0-131 months) diagnosed with an
      ADV infection were enrolled. Fever (99.0%) was by far the most frequent symptom,
      followed by respiratory (82.9%), and gastrointestinal (22.9%) symptoms. Upper and
      lower respiratory tract infections were diagnosed in 56 (53.3%), and 32 (30.5%)
      children, respectively. Five (4.8%) children received oxygen therapy, and no
      child died due to ADV infection. Coinfection was diagnosed in 32 (30.5%)
      children, with rhinovirus (46.9%), and respiratory syncytial virus (21.9%) being
      the most frequent. The proportions of children younger than 24 months (P <0.001),
      with underlying medical conditions (P = 0.020), and diagnosed with lower
      respiratory tract infection (P = 0.011) were significantly higher in the
      coinfection group than in the ADV group. In a multivariate analysis, only the
      younger age was significantly associated with coinfection (P <0.001). Although
      more children in the coinfection group received oxygen therapy (P = 0.029), the
      duration of fever and hospitalization was not significantly different between the
      two groups. CONCLUSION: Respiratory viral coinfection with ADV occurred more
      frequently in children younger than 24 months of age compared with children aged
      24 months or older. Respiratory viral coinfection may increase the severity of
      ADV infection, however, appropriate therapy prevented prolonged hospitalization
      and poor prognosis due to coinfection.

PMID- 27883374
TI  - Association between Body Mass Index and Sputum Culture Conversion among South
      Korean Patients with Multidrug Resistant Tuberculosis in a Tuberculosis Referral
      Hospital.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is an important global
      health problem. Furthermore, the time to identify a positive sputum culture is an
      important risk factor for the spread of tuberculosis, and several factors can
      predict a prolonged time to culture conversion. Moreover, the relationship
      between poor nutritional status and infectious disease is clearly established.
      Therefore, the present study aimed to investigate the association between body
      mass index (BMI) and sputum culture conversion within 3 months among patients
      with MDR-TB. MATERIALS AND METHODS: We retrospectively evaluated 218 patients
      with MDR-TB who were treated at a large tuberculosis referral hospital in South
      Korea between January 2005 and December 2010. The outcome of interest was defined
      as sputum culture conversion within 3 months, and we analyzed the association
      between BMI and this outcome. RESULTS: Among the 218 patients, 53 patients
      (24.3%) had a low BMI (<18.5 kg/m2). In the multivariate Cox proportional-hazards
      regression analysis, failure to achieve sputum culture conversion within 3 months
      was independently associated with having a low BMI (hazard ratio [HR]: 1.741, 95%
      confidence interval [CI]: 1.006-3.013; P = 0.047) and a positive sputum smear at
      the initiation of therapy (HR: 8.440, 95% CI: 1.146-62.138, P = 0.036).
      CONCLUSION: Low BMI (<18.5 kg/m2) was an independent risk factor for failure to
      achieve sputum culture conversion within 3 months among patients with MDR-TB.

PMID- 27883375
TI  - Analysis of Risk Factors for Severe Acute Respiratory Infection and Pneumonia and
      among Adult Patients with Acute Respiratory Illness during 2011-2014 Influenza
      Seasons in Korea.
AB  - BACKGROUND: The World Health Organization recommends the surveillance of
      influenza-like illness (ILI) and severe acute respiratory infection (SARI) to
      respond effectively to both seasonal influenza epidemics and pandemics. In Korea,
      the "Hospital-based Influenza Morbidity and Mortality (HIMM)" surveillance system
      has been operated to monitor ILI and SARI occurrences. MATERIALS AND METHODS: A
      multi-center prospective observational study was conducted. Adult patients with
      acute respiratory infection (ARI) were enrolled during the 2011-12, 2012-2013,
      and 2013-2014 influenza seasons at the 10 university hospitals using the HIMM
      surveillance system. With respect to SARI and pneumonia development, risk
      profiles were analyzed in patients with ARI in Korea. RESULTS: A total of 5,459
      cases were eligible for this analysis. Among 5,459 cases with ARI, 2,887 cases
      (52.9%) were identified that they had influenza infection. Among enrolled cases,
      750 cases belonged to the SARI group, while 4,709 cases belonged to the non-SARI
      group. With respect to pneumonia development, 317 cases were accompanied by
      pneumonia, and 5,142 cases were not. Multivariate analyses revealed that the
      following factors were associated with an increased risk of SARI: Old age (>=65
      years) (odds ratio [OR] 2.69, 95% confidence interval [CI] 2.2-3.32), chronic
      heart disease (CHD) (OR 2.24, 95% CI 1.68-2.98), cerebrovascular disease (CVD)
      (OR 1.49, 95% CI 1.05-2.10), chronic obstructive pulmonary disease (COPD) (OR
      2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62-3.36), chronic kidney
      disease (CKD) (OR 2.62, 95% CI 1.73-3.99), chronic liver disease (OR 1.71, 95% CI
      1.04-2.81), and autoimmune diseases (OR 2.53, 1.57-4.08). Multivariate analyses
      revealed that the following factors were independent risk factors for pneumonia
      development: Old age (>=65 years) (OR 5.71, 95% CI 4.10-7.94), CHD (OR 1.54, 95%
      CI 1.07-2.22), COPD (OR 2.34, 95% CI 1.48-3.69), asthma (OR 2.33, 95% CI 1.62
      3.36), CKD (OR 2.62, 95% CI 1.73-3.99), immunocompromised conditions (OR 3.12,
      95% CI 1.47-6.62), and autoimmune diseases (OR 3.35, 95% CI 1.79-6.27). The risk
      of SARI and pneumonia was increased by the number of concurrent chronic medical
      conditions. CONCLUSION: The risk of SARI and pneumonia development among adult
      patient with ARI was significantly increased by the presence or number of
      concurrent chronic medical conditions in Korea.

PMID- 27883376
TI  - Sensitivity of the Cytomegalovirus Antigenemia Assay to Diagnose Cytomegalovirus
      Retinitis.
AB  - BACKGROUND: Cytomegalovirus (CMV) retinitis is one of the most important tissue
      invasive CMV diseases in immunocompromised patients. Since 1980, non-invasive
      diagnostic methods, notably the CMV antigenemia assay, have been widely used as
      adjunct tests to diagnose tissue-invasive CMV diseases. However, there are
      limited data on the diagnostic value of the CMV antigenemia assay for diagnosing
      CMV retinitis. MATERIALS AND METHODS: We performed a retrospective review of all
      cases of CMV retinitis at Asan Medical Center, Seoul, South Korea over a 9-year
      period. The diagnosis of CMV retinitis was made by experienced ophthalmologists
      according to medical history and an ophthalmoscopic appearance of typical
      retinopathy, together with absence of an alternative diagnosis. RESULTS: We
      analyzed 44 patients with CMV retinitis (affecting 57 eyes) for whom the CMV
      antigenemia assay was performed. Of the 44 patients, 31 (70%) were HIV-uninfected
      and 13 (30%) were HIV-infected. The overall sensitivity of the CMV antigenemia
      assay was 66% (95% confidence interval [CI] 50-80%). The test's sensitivity
      showed a non-significant trend towards being higher in HIV-infected patients than
      in HIV-uninfected patients (sensitivity 85% vs 58%, respectively, P = 0.16). In a
      subgroup analysis of the 35 patients without other concurrent tissue-invasive CMV
      disease, the sensitivity of the CMV antigenemia assay was 57% (95% CI 40-74%).
      CONCLUSIONS: The CMV antigenemia assay has limited value as a non-invasive
      diagnostic adjunct test for CMV retinitis. Therefore, the results of the assay
      need to be interpreted in the context of underlying disease, clinical
      presentation, and ophthalmoscopic findings.

PMID- 27883377
TI  - Borrelia burgdorferi - morphological structure and motility as adaptation for
      transmission and survival in the habitat of a tick-vertebrate setup
AB  - Lyme borreliosis is a multisystem chronic disease caused by Borrelia burgdorferi
      sensu lato (s.l.) spirochete transmitted by Ixodes. This bacterium has a
      remarkable ability to survive in tick-vertebrate setup. Its infection causes
      diagnostic and clinical difficulties. It was distinguished as a separate disease
      entity over 30 years ago. Observations made by Steere et al. proved to be a
      milestone since they found correlation between the occurrence of skin and joint
      lesions with tick bites. Further studies showed that the disease affects not only
      joints and skin, but also nervous and circulatory systems. Shortly afterwards, an
      etiological factor was identified - spirochete isolated by W. Burgdorfer (from
      ticks) as well as Steer and Benach (from blood). Research conducted by other
      authors confirmed that the spirochete named after its discoverer (Borrelia
      burgdorferi) is a common etiological factor for disease entities classified as
      Lyme borreliosis. The high incidence of Lyme borreliosis among the residents of
      endemic areas, along with diagnostic and therapeutic difficulties, make it a
      serious academic, clinical and social problem. The present article elaborates on
      bacterium structure and selected mechanisms facilitating the colonisation of
      particular hosts. Knowledge of those processes might be useful in understanding
      complex pathogenesis of lesions occurring in Lyme disease.

PMID- 27883378
TI  - Wild animals as reservoirs of Anaplasma phagocytophilum for humans
AB  - Anaplasma phagocytophilum is a tick-transmitted obligate-intracellular gram
      negative bacteria that causes emerging human zoonosis. A. phagocytophilum is
      transmitted by Ixodid ticks. Recent studies suggest that wild animals may be
      reservoirs of A. phagocytophilum for humans. The organism infects and survives
      within neutrophils. The infection diagnosis is based on the detection of morulae
      within granulocytes of peripheral  blood, results of serological tests and
      detection of the DNA of A. phagocytophilum using specific polymerase chain
      reaction assays (PCR). A. phagocytophilum in most cases is transmitted to people
      by tick bites, but sometimes direct contact with infected blood may cause human
      granulocytic anaplasmosis (HGA). The possibility of infection should be taken
      into consideration at each occurrence of heavy disease symptoms after people come
      into contact with ticks.

PMID- 27883379
TI  - Epidemiological and clinical features of tick-borne encephalitis in north-western
      region in Belarus
AB  - THE PURPOSE OF THE STUDY: to present epidemiological features and clinical
      manifestations of TBE in patients residing in Grodno region. MATERIALS AND
      METHODS: A retrospective analysis of 124 case histories of patients with TBE in
      "Grodno Regional Infectious Clinical Hospital" in 2010 - 2014. RESULTS:
      Epidemiological features of tick-borne encephalitis are the prevalence of the
      transmission mechanism of contamination (57.3%), involvement of residents of
      Grodno and Grodno region (54.2%) of middle age (46.6+/-3.5 years) in the epidemic
      process. Clinical features of the illness in 124 patients were the prevalence of
      moderate forms of the illness (72%) in the form of meningeal (34.6%) and common
      infectious (29%) clinical cases. CONCLUSIONS: Over the last 5 years in Grodno
      region an increased incidence of tick-borne encephalitis exceeding republican
      indices has been established. Among clinical cases there is an increase in severe
      forms of neuroinfections and mixed tick-borne.

PMID- 27883411
TI  - Acute liver failure during treatment of interferon alpha 2a chronic hepatitis B
      and coinfection of parvovirus B19
AB  - Parvovirus B19 infection is associated with a broad spectrum of clinical
      manifestations among which some are well known but others remain controversial.
      The role of this infection as a cause of acute hepatitis or exacerbation of
      chronic liver disease requires discussion regarding its significance in a
      strategy of prevention and treatment of patients with chronic hepatitis. Clinical
      importance of this infection in patients with chronic hepatitis B treatedwith
      pegylated interferon alpha 2a is still unclear but exactly in this population
      significant complications during treatment may arise. Parvovirus B19 infection is
      not rare among persons with chronic hepatitis B, therefore searching for co
      infection should be placed in standard diagnostic procedures especially in case
      of exacerbation of chronic hepatitis, pancytopaenia or anaemia of unknown origin.
      Pegylated interferon alpha 2a still remains a gold standard of therapy of
      patients with chronic hepatitis B according to European (EASL) and Polish
      guidelines. We present a case of 35 years old woman treated with pegylated
      interferon alpha 2a who developed acute liver failure in 23rd week of chronic
      hepatitis B therapy. An exacerbation of hepatitis with encephalopathy and
      pancytopaenia have been observed. Parvovirus B19 and HBV co-infection does not
      increase the frequency of liver function abnormalities in patients with chronic
      hepatitis B. Further investigations should be done to describe the natural course
      of co-infection with parvovirus B19 and HBV and to establish possible association
      between parvovirus B19 infection and chronic hepatitis B and also the influence
      of interferon alpha 2a on the infections course.

PMID- 27883412
TI  - Prolonged hospitalization of patients with hospital acquired pneumoniae in the
      intensive care unit - morbidity, mortality and costs of
AB  - BACKGROUND: The objective of this study was to determine epidemiological rates of
      hospital-acquired pneumonia (HAP) in the Polish ICU and direct costs associated
      with excess length of stay incurred by the hospital. MATERIAL AND METHODS: The
      studied data concern patients hospitalized in the years 2010-2012 in a 9-bed ICU
      of a multi-profile hospital in the Malopolskie Province. Centers for Disease
      Control and Prevention diagnostic criteria were the basis for the development of
      definitions of infections. RESULTS: HAP developed in 34 patients, of which 94.1%
      were cases associated with the use of mechanical ventilation. Cumulative
      incidence of HAP was 5.74%, and incidence density amounted to 3.000/00. Median
      length of stay of patients with HAP amounted to 36 days and this value was more
      than twenty percent higher than in the case of other forms of infection (27
      days), and almost three times higher than in patients without infections (14
      days). Annually, costs associated with the excess hospitalization of patients
      with this form of infection should be evaluatedat over PLN 300,000 (72.290?) per
      hospital; average per patient is PLN 29,106 (7013?). CONCLUSIONS: HAP is one of
      the most common hospital-acquired infections in intensive care units. It is
      connected with the greatest additional costs for hospital comparing to other
      forms of HAIs. For patients, the occurrence of HAP in ICU patients involves the
      highest risk of death. Detailed, targeted studies concerning financial burden of
      HAI in Poland should be performed.

PMID- 27883872
TI  - Evidence-based review, not change in usage patterns, should drive Medicare
      Benefit Schedule (MBS) disinvestment decisions.

PMID- 27883873
TI  - Doctors' attitudes regarding not for resuscitation orders.
AB  - Objectives The aims of the present study were to investigate doctors' attitudes
      regarding the discussion and writing of not for resuscitation (NFR) orders and to
      identify potential barriers to the completion of these orders. Methods A
      questionnaire-based convenience study was undertaken at a tertiary hospital.
      Likert scales and open-ended questions were directed to issues surrounding the
      discussion, timing, understanding and writing of NFR orders, including legal and
      personal considerations. Results Doctors thought the presence of an NFR order
      both should and does alter care delivered by nursing staff, particularly delivery
      of pain relief, nursing observations and contacting the medical emergency team.
      Eighty-five per cent of doctors believed they needed somebody else's consent to
      write an NFR order (seeking of consent is not a requirement in most Australian
      jurisdictions). Conclusion There are complex barriers to the writing and
      implementation of NFR orders, including doctors' knowledge around the need for
      consent when cardiopulmonary resuscitation is likely to be futile or excessively
      burdensome. Doctors also believed that NFR orders result in changes to goals-of
      care, suggesting a confounding of NFR orders with palliative care. Furthermore,
      doctors are willing to write NFR orders where there is clear medical indication
      and the patient is imminently dying, but are otherwise reliant on patients and
      family to initiate discussion. What is known about the topic? Hospitalised
      elderly patients, in the absence of an NFR order, are known to have poor survival
      and outcomes following resuscitation. Further, Australian data on the prevalence
      of NFR forms show that only a minority of older in-patients have a written NFR
      order in their history. In Australian hospitals, NFR orders are completed by
      doctors. What does this paper add? To our knowledge, the present study is the
      first in Australia to qualitatively analyse doctors' reasons to writing NFR
      orders. The open-text nature of this questioning has been important in eliciting
      doctors' responses without hypothesis guessing bias. Further, we add to the
      literature on the breadth of considerations doctors may encounter with regard to
      NFR orders. What are the implications for practitioners? The findings indicate
      the issues impeding decision making around cardiopulmonary resuscitation relate
      to poor knowledge of the law, particularly around the issue of consent and
      confounding NFR orders with provision of palliative care. Such barriers to the
      completion of NFR orders expose elderly in-patients to futile and burdensome
      resuscitation events. The findings suggest consideration be given to education
      and training materials to inform doctors about jurisdictional law regarding
      resuscitation documentation, support decision making around cardiopulmonary
      resuscitation and promote goals-of-care discussions on admission.

PMID- 27883874
TI  - Structured interdisciplinary bedside rounds do not reduce length of hospital stay
      and 28-day re-admission rate among older people hospitalised with acute illness:
      an Australian study.
AB  - Objective Structured interdisciplinary bedside rounds (SIBR) are being
      implemented across many hospitals in Australia despite limited evidence of their
      effectiveness. This study evaluated the effect of SIBR on two interconnected
      outcomes, namely length of stay (LOS) and 28-day re-admission. Methods In the
      present before-after study of 3644 patients, twice-weekly SIBR were implemented
      on two aged care wards. Although weekly case conferences were shortened during
      SIBR, all other practices remained unchanged. Demographic, medical and frailty
      measures were considered in appropriate analyses. Results There was no
      significant difference in median (interquartile range) LOS before and during SIBR
      (8 (5-15) vs 8 (4-15) days respectively; P=0.51). In an adjusted analysis, SIBR
      had no effect on LOS (hazard ratio 0.97; 95% confidence interval 0.90-1.05). The
      presence of dementia or delirium, or the ability to speak English, did not modify
      the effect of SIBR (P>0.05 for all). Similarly, SIBR had no effect on 28-day re
      admission rates (20.3% vs 19.0% before and during SIBR respectively; P=0.36).
      Conclusions Although ineffective interdisciplinary communication is associated
      with negative outcomes for patients and healthcare services, models of care that
      aim to improve communication are not necessarily effective in reducing LOS or
      early re-admission. Clinical services implementing SIBR are encouraged to
      independently evaluate their effects. What is known about the topic? Ineffective
      interdisciplinary communication may harm patients and increase LOS. Only two
      publications have evaluated the implementation of SIBR, a new model of care that
      aims to improve interdisciplinary communication and collaboration. One paper
      reported that SIBR reduced unadjusted LOS and in-hospital mortality, whereas the
      other found that SIBR improved teamwork, communication and staff efficiency. What
      does this paper add? The effect of SIBR among acutely unwell older people on aged
      care wards is unknown. The present study is the first to evaluate the effects of
      SIBR in this population. It shows that the implementation of SIBR did not reduce
      LOS or early re-admission, and suggests that existing communication strategies
      may have weakened the effects of SIBR. What are the implications for
      practitioners? Policies and practice that promote the addition of communication
      strategies, such as SIBR, may not be effective in all patient populations. More
      research is needed to determine whether SIBR reduce these and other outcomes,
      particularly for services with weaker communication frameworks and protocols.

PMID- 27883875
TI  - A case of urinary tract infection caused by Raoultella planticola after a
      urodynamic study.
AB  - Here we report the case of a patient who developed urinary tract infection after
      a urodynamic study. The causative agent was Raoultella planticola, a rare
      opportunistic pathogen that usually invades immunocompromised patients. While a
      urinary tract infection with R. planticola has been previously described, this is
      the first report in which an R. planticola infection developed after a urodynamic
      study. We postulate that the mechanism of infection was direct invasion of the
      urinary tract from contaminated urodynamic study equipment. Here, we discuss the
      role played by isotonic solutions in facilitating bacterial reproduction.

PMID- 27883877
TI  - Surgical Management of Progressive Hemifacial Atrophy With De-Epithelialized
      Profunda Artery Perforator Flap: A Case Report.
AB  - Progressive hemifacial atrophy (PHA) is a rare disorder characterized by slow,
      unilateral atrophy of the soft tissues and bones of the craniofacial region. The
      defect becomes more pronounced with age, leading to esthetic and functional
      deficits. However, the proper timing and method of surgical reconstruction are
      still debated. The correction of this defect markedly influencing the quality of
      life of the patient can be achieved with less invasive to more invasive surgical
      approaches. A 21-year-old female patient with hemifacial atrophy and extensive
      alopecia presented to our clinic. Considering the body type and the expectations
      of the patient, a profunda artery perforator flap was applied for the
      reconstruction and esthetic improvement of the facial region. The facial
      asymmetry attenuated after the reconvalescence period. This case shows that in
      the up-to-date surgical treatment of severe PHA, the use of microvascular free
      flaps may provide a better approach when trying to achieve an acceptable esthetic
      result. This is the first time that a profunda artery perforator flap was used to
      restore facial asymmetry caused by PHA.

PMID- 27883876
TI  - Comprehensive Genomic Profiling of Central Giant Cell Lesions Identifies
      Clinically Relevant Genomic Alterations.
AB  - PURPOSE: Comprehensive genomic profiling (CGP) can simultaneously detect
      clinically relevant genomic alterations (CRGAs) in hundreds of cancer-related
      genes and direct treatment toward patient-specific therapy options for many
      tumors. This pilot study aimed to use CGP to describe CRGAs present in central
      giant cell lesions (CGCLs) to characterize any possible underlying genomic
      drivers of CGCLs. MATERIALS AND METHODS: With institutional review board
      approval, electronic medical records were searched for patients with
      histologically confirmed CGCLs who underwent biopsy at Mayo Clinic from 2000
      through 2014. Clinical characteristics were recorded from the medical records. At
      least 50 ng of DNA was extracted from formalin-fixed paraffin-embedded archival
      CGCL specimens by use of hybridization-capture, adaptor ligation-based libraries
      targeting all exons from 315 cancer-related genes plus select introns from 28
      genes commonly rearranged in cancer. Samples were sequenced to high, uniform
      coverage and assessed for all 4 classes of genomic alterations: base
      substitutions, small insertions and deletions, rearrangements, and copy number
      alterations. RESULTS: Of 8 CGCL specimens, 3 (37.5%) harbored CRGAs, including
      base substitutions in BRAF, GNAS, and KRAS that are predicted to be oncogenic. In
      1 sample, focal high-level amplification of the MITF gene was detected.
      Rearrangement in the PDGFRB gene was identified in a fourth sample, although the
      significance of this alteration is uncertain. CONCLUSIONS: This pilot study shows
      that a relatively high frequency of CRGAs (37.5%) can be identified in CGCLs by
      use of CGP. Furthermore, 25% of CGCLs analyzed had somatic mutations predicted to
      activate the mitogen-activated protein kinase signaling pathway, suggesting it
      may be a driver of the aggressive behavior of these lesions. On the basis of this
      study, genomic profiling of a larger cohort of CGCLs to validate these
      observations, as well as correlate mutations with aggressive versus nonaggressive
      biological behavior and therapeutic responses, appears warranted.

PMID- 27883878
TI  - Effect of the Postpartum Hospital Environment on the Attainment of Mothers' and
      Fathers' Goals.
AB  - OBJECTIVE: To describe mothers' and fathers' goals in the postpartum period and
      how the hospital environment enables or hinders the attainment of these goals.
      DESIGN: A qualitative descriptive design was used to explore participants'
      perceptions. SETTING: Mothers and fathers were recruited on the postpartum unit
      of an urban hospital. PARTICIPANTS: Ten mothers and eight fathers participated.
      METHODS: Semistructured interviews were conducted with mothers and fathers
      individually. Data analysis occurred concurrently with data collection and
      informed subsequent interviews. RESULTS: Mothers and fathers expressed similar
      goals: developing parenting competence and fulfilling personal needs. Their
      narratives indicated that the organizational environment with the mission to
      promote and provide baby-friendly and family-centered care and the human
      environment of responsive nursing were closely aligned with their goals. In
      contrast, the routines of the unit and the physical environment were not
      consistent with parents' goals or the mission of the organization. CONCLUSION:
      Nurses have important advocacy roles in ensuring that all dimensions of the
      postpartum environment support the ability of parents to attain their goals and
      align with the philosophy of care of the organization.

PMID- 27883880
TI  - The 40th Anniversary and Counting of the Nurses' Health Study.

PMID- 27883879
TI  - Challenging Expected Patterns of Weight Loss in Full-Term Breastfeeding Neonates
      Born by Cesarean.
AB  - OBJECTIVE: To determine the mean weight loss (MWL) of newborns and to examine the
      effect of weight loss > 7% on exclusive breastfeeding rates. DESIGN: A secondary
      analysis from a retrospective case-control study of maternal hydration and
      neonatal weight. SETTING: A Level III maternity hospital in the Northeast region
      of the United States. PARTICIPANTS: A total of 286 women and their term
      breastfeeding newborns born by cesarean. METHODS: Data were collected by chart
      review from birth through Days 3 or 4. Newborns who lost more than 7% of birth
      weight by Day 3 were included in the case group, and newborns who lost 7% or less
      by Day 3 were included in the control group. A significance level of .05 was used
      for all statistical analysis. RESULTS: Day 3 MWL for all newborns was 8% (n =
      286, 7.9% +/- 2.2%). MWL for the control group (n = 121) was 6% (5.93% +/-
      1.31%), and MWL for the case group (n = 165) was over 9% (9.35% +/- 1.38%).
      Predominately breastfed newborns were still losing weight on Day 4 (MWL = 7.58%).
      Newborns who lost 7% or less had little change in exclusive breastfeeding, from
      87% to 80% by Day 4. In contrast, exclusive breastfeeding in newborns who lost
      more than 7% dropped markedly, from 90% to 53% (p < .001). CONCLUSION: Weight
      loss of more than 7% appears to be a normal phenomenon among full-term newborns.
      When weight loss reached 7%, formula supplementation increased markedly.
      Predominately breastfed newborns are most at risk for continued weight loss after
      hospital discharge.

PMID- 27883882
TI  - Editorial Comment.

PMID- 27883883
TI  - Commendation for Interdisciplinary Peer Review.

PMID- 27883881
TI  - Sofosbuvir and Daclatasvir Anti-Viral Therapy Fails to Clear HEV Viremia and
      Restore Reactive T Cells in a HEV/HCV Co-Infected Liver Transplant Recipient.

PMID- 27883884
TI  - Principles of Systems Biology, No. 11.
AB  - This month: AI that learns patterns and facts, new protein-RNA and protein
      protein relationships, engineering signaling and metabolism, and more variants of
      Cas9.

PMID- 27883885
TI  - Commendation for Exposing Key Advantage of Organ Chip Approach.

PMID- 27883886
TI  - CHO Cells Can Make More Protein.
AB  - A new comprehensive genome-scale metabolic model of Chinese hamster ovary cells
      identifies pathways for improving biopharmaceutical protein production.

PMID- 27883887
TI  - Signaling Tug-of-War Delivers the Whole Message.
AB  - How do cells transmit biochemical signals accurately? It turns out, pushing and
      pulling can go a long way.

PMID- 27883888
TI  - Personalized Disease Models on a Chip.
AB  - Organs-on-chips are beginning to serve as a useful platform for individualized
      disease models in a way that minimizes patient-to-patient variability.

PMID- 27883889
TI  - Inferring Cell-State Transition Dynamics from Lineage Trees and Endpoint Single
      Cell Measurements.
AB  - As they proliferate, living cells undergo transitions between specific
      molecularly and developmentally distinct states. Despite the functional
      centrality of these transitions in multicellular organisms, it has remained
      challenging to determine which transitions occur and at what rates without
      perturbations and cell engineering. Here, we introduce kin correlation analysis
      (KCA) and show that quantitative cell-state transition dynamics can be inferred,
      without direct observation, from the clustering of cell states on pedigrees
      (lineage trees). Combining KCA with pedigrees obtained from time-lapse imaging
      and endpoint single-molecule RNA-fluorescence in situ hybridization (RNA-FISH)
      measurements of gene expression, we determined the cell-state transition network
      of mouse embryonic stem (ES) cells. This analysis revealed that mouse ES cells
      exhibit stochastic and reversible transitions along a linear chain of states
      ranging from 2C-like to epiblast-like. Our approach is broadly applicable and may
      be applied to systems with irreversible transitions and non-stationary dynamics,
      such as in cancer and development.

PMID- 27883891
TI  - Analysis of Cell Lineage Trees by Exact Bayesian Inference Identifies Negative
      Autoregulation of Nanog in Mouse Embryonic Stem Cells.
AB  - Many cellular effectors of pluripotency are dynamically regulated. In principle,
      regulatory mechanisms can be inferred from single-cell observations of effector
      activity across time. However, rigorous inference techniques suitable for noisy,
      incomplete, and heterogeneous data are lacking. Here, we introduce stochastic
      inference on lineage trees (STILT), an algorithm capable of identifying
      stochastic models that accurately describe the quantitative behavior of cell fate
      markers observed using time-lapse microscopy data collected from proliferating
      cell populations. STILT performs exact Bayesian parameter inference and
      stochastic model selection using a particle-filter-based algorithm. We use STILT
      to investigate the autoregulation of Nanog, a heterogeneously expressed core
      pluripotency factor, in mouse embryonic stem cells. STILT rejects the possibility
      of positive Nanog autoregulation with high confidence; instead, model predictions
      indicate weak negative feedback. We use STILT for rational experimental design
      and validate model predictions using novel experimental data. STILT is available
      for download as an open source framework from
      http://www.imsb.ethz.ch/research/claassen/Software/stilt---stochastic-inference
      on-lineage-trees.html.

PMID- 27883892
TI  - Vimentin Intermediate Filaments Template Microtubule Networks to Enhance
      Persistence in Cell Polarity and Directed Migration.

PMID- 27883890
TI  - A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism.
AB  - Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and
      are widely used in mammalian cell line engineering research. To elucidate
      metabolic bottlenecks in protein production and to guide cell engineering and
      bioprocess optimization, we reconstructed the metabolic pathways in CHO and
      associated them with >1,700 genes in the Cricetulus griseus genome. The genome
      scale metabolic model based on this reconstruction, iCHO1766, and cell-line
      specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical
      basis of growth and recombinant protein production. The models accurately predict
      growth phenotypes and known auxotrophies in CHO cells. With the models, we
      quantify the protein synthesis capacity of CHO cells and demonstrate that common
      bioprocess treatments, such as histone deacetylase inhibitors, inefficiently
      increase product yield. However, our simulations show that the metabolic
      resources in CHO are more than three times more efficiently utilized for growth
      or recombinant protein synthesis following targeted efforts to engineer the CHO
      secretory pathway. This model will further accelerate CHO cell engineering and
      help optimize bioprocesses.

PMID- 27883894
TI  - An examination of the construct and predictive validity of the self-reported
      speeding behavior model.
AB  - The present study deals with the problem of speeding behavior on rural roads. The
      purpose of the paper is to examine the construct validity and the internal
      consistency and reliability of a questionnaire that measures the determinants of
      speeding behavior. In addition, it aimed to test the predictive validity of a
      modified theoretical framework of a theory of planned behavior (TPB) in relation
      to speeding behavior. A total of 546 car drivers from five local communities in
      the Republic of Srpska successfully completed the questionnaire after reading the
      scenario. The principal component analysis revealed seven components interpreted
      as: personal norm, perceived behavioral control, affective attitude toward
      speeding, subjective norm, habit, descriptive norm, and cognitive attitude toward
      speeding. A speeding behavior model was developed by structural equation
      modeling. Personal norm, subjective norm, and affective attitudes were shown to
      be important variables within the modified TPB in understanding speeding
      behavior. Overall, the present findings provide significant support for the
      concept of the modified theoretical framework of TPB in relation to speeding
      behavior on rural roads. Implications for a speeding behavior model and
      interventions are discussed.

PMID- 27883893
TI  - Circadian alterations during early stages of Alzheimer's disease are associated
      with aberrant cycles of DNA methylation in BMAL1.
AB  - INTRODUCTION: Circadian alterations are prevalent in Alzheimer's disease (AD) and
      may contribute to cognitive impairment, behavioral symptoms, and
      neurodegeneration. Epigenetic mechanisms regulate the circadian clock, and
      changes in DNA methylation have been reported in AD brains, but the pathways that
      mediate circadian deregulation in AD are incompletely understood. We hypothesized
      that aberrant DNA methylation may affect circadian rhythms in AD. METHODS: We
      investigated DNA methylation, transcription, and expression of BMAL1, a positive
      regulator of the circadian clock, in cultured fibroblasts and brain samples from
      two independent cohorts of aging and AD. RESULTS: DNA methylation modulated
      rhythmic expression of clock genes in cultured fibroblasts. Moreover, rhythmic
      methylation of BMAL1 was altered in AD brains and fibroblasts and correlated with
      transcription cycles. DISCUSSION: Our results indicate that cycles of DNA
      methylation contribute to the regulation of BMAL1 rhythms in the brain. Hence,
      aberrant epigenetic patterns may be linked to circadian alterations in AD.

PMID- 27883895
TI  - Disentangling the roles of safety climate and safety culture: Multi-level effects
      on the relationship between supervisor enforcement and safety compliance.
AB  - Despite increasing attention to contextual effects on the relationship between
      supervisor enforcement and employee safety compliance, no study has yet explored
      the conjoint influence exerted simultaneously by organizational safety climate
      and safety culture. The present study seeks to address this literature
      shortcoming. We first begin by briefly discussing the theoretical distinctions
      between safety climate and culture and the rationale for examining these
      together. Next, using survey data collected from 1342 employees in 32 Italian
      organizations, we found that employee-level supervisor enforcement,
      organizational-level safety climate, and autocratic, bureaucratic, and
      technocratic safety culture dimensions all predicted individual-level safety
      compliance behaviors. However, the cross-level moderating effect of safety
      climate was bounded by certain safety culture dimensions, such that safety
      climate moderated the supervisor enforcement-compliance relationship only under
      the clan-patronage culture dimension. Additionally, the autocratic and
      bureaucratic culture dimensions attenuated the relationship between supervisor
      enforcement and compliance. Finally, when testing the effects of technocratic
      safety culture and cooperative safety culture, neither safety culture nor climate
      moderated the relationship between supervisor enforcement and safety compliance.
      The results suggest a complex relationship between organizational safety culture
      and safety climate, indicating that organizations with particular safety cultures
      may be more likely to develop more (or less) positive safety climates. Moreover,
      employee safety compliance is a function of supervisor safety leadership, as well
      as the safety climate and safety culture dimensions prevalent within the
      organization.

PMID- 27883896
TI  - The Importance of Planning in Motor Learning.
AB  - The addition of differentiating follow-through motions can facilitate
      simultaneous learning of multiple motor skills that would otherwise interfere
      with each other. In this issue of Neuron, Sheahan and colleagues (2016)
      demonstrate that it is the preparation, not execution, of different follow
      through movements that separates motor memories and reduces interference.

PMID- 27883897
TI  - hnRNPA2/B1 Function in Neurodegeneration: It's a Gain, Not a Loss.
AB  - hnRNPA2B1 is linked to several neurodegenerative disorders, yet its roles in the
      CNS have been largely unknown. In this issue of Neuron, Martinez et al. (2016)
      present the first transcriptome-wide analysis of hnRNPA2B1 targets and function
      in the nervous system.

PMID- 27883898
TI  - Autophagosome Formation by Endophilin Keeps Synapses in Shape.
AB  - Soukup et al. (2016), in this issue of Neuron, and Murdoch et al. (2016), in Cell
      Reports, reveal an unexpected function for the endocytic protein endophilin in
      autophagosome formation at synapses: preventing neurodegeneration and ataxia.

PMID- 27883899
TI  - Cut Your Losses: Spastin Mediates Branch-Specific Axon Loss.
AB  - In this issue of Neuron, Brill et al. (2016) demonstrate that, during synapse
      elimination in the developing neuromuscular junction, branch-specific microtubule
      destabilization results in arrested axonal transport and induces axon branch
      loss. This process is mediated in part by the neurodegeneration-associated,
      microtubule-severing protein spastin.

PMID- 27883900
TI  - Primate Neurons Flex Their Musclin.
AB  - Sensory experience evokes long-lasting changes in neural circuits through
      activity-dependent gene expression. Ataman et al. (2016) report in Nature that
      primates evolved novel transcriptional responses to neuronal activity, including
      induction of musclin/osteocrin (OSTN), which may regulate specialized aspects of
      primate neural circuits.

PMID- 27883903
TI  - NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk.

PMID- 27883904
TI  - Enabling an Open Data Ecosystem for the Neurosciences.

PMID- 27883905
TI  - Molecularly Defined Circuitry Reveals Input-Output Segregation in Deep Layers of
      the Medial Entorhinal Cortex.

PMID- 27883901
TI  - Tapping the Brakes: Cellular and Synaptic Mechanisms that Regulate Thalamic
      Oscillations.
AB  - Thalamic oscillators contribute to both normal rhythms associated with sleep and
      anesthesia and abnormal, hypersynchronous oscillations that manifest behaviorally
      as absence seizures. In this review, we highlight new findings that refine
      thalamic contributions to cortical rhythms and suggest that thalamic oscillators
      may be subject to both local and global control. We describe endogenous thalamic
      mechanisms that limit network synchrony and discuss how these protective brakes
      might be restored to prevent absence seizures. Finally, we describe how intrinsic
      and circuit-level specializations among thalamocortical loops may determine their
      involvement in widespread oscillations and render subsets of thalamic nuclei
      especially vulnerable to pathological synchrony.

PMID- 27883902
TI  - Circuit Mechanisms of Sensorimotor Learning.
AB  - The relationship between the brain and the environment is flexible, forming the
      foundation for our ability to learn. Here we review the current state of our
      understanding of the modifications in the sensorimotor pathway related to
      sensorimotor learning. We divide the process into three hierarchical levels with
      distinct goals: (1) sensory perceptual learning, (2) sensorimotor associative
      learning, and (3) motor skill learning. Perceptual learning optimizes the
      representations of important sensory stimuli. Associative learning and the
      initial phase of motor skill learning are ensured by feedback-based mechanisms
      that permit trial-and-error learning. The later phase of motor skill learning may
      primarily involve feedback-independent mechanisms operating under the classic
      Hebbian rule. With these changes under distinct constraints and mechanisms,
      sensorimotor learning establishes dedicated circuitry for the reproduction of
      stereotyped neural activity patterns and behavior.

PMID- 27883907
TI  - Bimodal concentration-dependent reactivity pattern of a glycosyl donor: Is the
      solution structure involved?
AB  - Changes in concentration (0.001-0.1 M) of an arabinofuranosyl donor (1) have been
      shown to modulate the temperature T at which activation of 1 occurs (from -23 
      degrees C to +7  degrees C), the reaction time (from 1.5 h to 3 days) and the
      yield of the disaccharide formed (from 14% to 82%). At concentrations exceeding
      0.01 M, these parameters, as well as the specific optical rotation of the
      solution of 1, virtually do not depend on concentration suggesting formation of
      reacting species (supramers) of glycosyl donor with similar structures, hence
      reactivities, but considerably different from those formed in more dilute
      solutions. The found critical concentration (0.01 M) separates two concentration
      ranges of reaction solutions corresponding to two types of solution structure
      that are featured by the presence of fundamentally different supramers of
      glycosyl donor, which have distinct chemical properties. These results allow a
      fresh look at the problems of reactivity of chemical compounds and selectivity of
      the reactions in which they participate.

PMID- 27883908
TI  - Scalable preparation, characterization, and application of alkali-treated starch
      as a new organic base catalyst.
AB  - Preparation, characterization, and application of alkali starch (AS) given by dry
      co-grinding of starch and alkali is described in this work. Grinding using a
      mortar (agate) and pestle or, more conveniently, a ball mill has been found to be
      satisfactory for the preparation of the AS. The AS products were characterized by
      scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy
      (FTIR) and x-ray fluorescence (XRF) analyses. The base capacities of ASs were
      4.25-4.45 mmol/g, respectively. AS is a low cost and easy to handle base catalyst
      that showed promising catalytic performance in the synthesis of a
      dihydroquinazoline-based antibacterial drug that involves tandem hydration or
      decarboxylative amidation, imination, and Aza-Michael reactions.

PMID- 27883906
TI  - Infant food applications of complex carbohydrates: Structure, synthesis, and
      function.
AB  - Professional health bodies such as the World Health Organization (WHO), the
      American Academy of Pediatrics (AAP), and the U.S. Department of Health and Human
      Services (HHS) recommend breast milk as the sole source of food during the first
      year of life. This position recognizes human milk as being uniquely suited for
      infant nutrition. Nonetheless, most neonates in the West are fed alternatives by
      6 months of age. Although inferior to human milk in most aspects, infant formulas
      are able to promote effective growth and development. However, while breast-fed
      infants feature a microbiota dominated by bifidobacteria, the bacterial flora of
      formula-fed infants is usually heterogeneous with comparatively lower levels of
      bifidobacteria. Thus, the objective of any infant food manufacturer is to prepare
      a product that results in a formula-fed infant developing a breast-fed infant
      like microbiota. The goal of this focused review is to discuss the structure,
      synthesis, and function of carbohydrate additives that play a role in governing
      the composition of the infant microbiome and have other health benefits.

PMID- 27883909
TI  - Anti-inflammatory effect of a fatty acid mixture with high omega-9:omega-6 ratio
      and low omega-6:omega-3 ratio on rats submitted to dental extraction.
AB  - OBJECTIVE: To evaluate the anti-inflammatory effect of pretreatment for three
      days with a fatty acid mixture with high omega-9:omega-6 ratio and low omega
      6:omega-3 ratio on rats submitted to dental extraction. MATERIAL AND METHODS:
      Thirty-two male Wistar rats (270-310g) were randomly distributed in four groups
      (n=8/group): the sham control group and the negative control group received
      saline; the high omega-6/low omega-9 group received isolipid fatty acid with high
      omega-6:omega-3 ratio and low omega-9:omega-6 ratio; the high omega-3/low omega-6
      group received fatty acid with low omega-6:omega-3 ratio and high omega-9:omega-6
      ratio. Saline and oils were administered by gavage for 4days before exodontia and
      3days after surgery, followed by euthanasia. Masseter edema was evaluated
      clinically and tissue samples were submitted to osteoclast count (H&E),
      myeloperoxidase assay, and western blotting (tumor necrosis factor-alpha and
      interleukin-1beta). RESULTS: In the high omega-3/low omega-6 group, a significant
      decrease was observed in masseter edema (p<0.0001), myeloperoxidase (p<0.0001),
      osteoclasts (p=0.0001) and TNF-alpha expression (p<0.0001), but not in IL-1beta
      expression. CONCLUSION: The ingestion of fatty acid with high omega-9:omega-6
      ratio and low omega-6:omega-3 ratio significantly reduced inflammatory response
      in rats submitted to dental extraction.

PMID- 27883910
TI  - Influence of reduced glutathione on end-joining of DNA double-strand breaks:
      Cytogenetical and molecular approach.
AB  - Radiation induced DNA double-strand breaks (DSB) are the major initial lesions
      whose misrejoining may lead to exchange aberrations. However, the role of
      glutathione (GSH), a major cellular thiol, in regulating cell's sensitivity to
      DNA damaging agents is not well understood. Influence of endogenous GSH on the
      efficiency of X-rays and bleomycin (Blem) induced DNA DSBs end-joining has been
      tested here cytogenetically, in human lymphocytes and Hct116 cells. In another
      approach, oligomeric DNA (75bp) containing 5'-compatible and non-compatible
      overhangs mimicking the endogenous DSB were for rejoining in presence of cell
      free extracts from cells having different endogenous GSH levels. Frequency of
      aberrations, particularly exchange aberrations, was significantly increased when
      Blem was combined with radiation. The exchange aberration frequency was further
      enhanced when combined treatment was given at 4 degrees C since DNA lesions are
      poorly repaired at 4 degrees C so that a higher number of DNA breaks persist and
      interact when shifted from 4 degrees C to 37 degrees C. The exchange aberrations
      increased further when the combined treatment was given to Glutathione-ester (GE)
      pre-treated cells, indicating more frequent rejoining of DNA lesions in presence
      of higher cellular GSH. This is further supported by the drastic reduction in
      frequency of exchange aberrations but significant increase in incidences of
      deletions when combined treatment was given to GSH-depleted cells. End-joining
      efficiency of DNA DSBs with compatible ends was better than for non-compatible
      ends. End-joining efficiency of testicular and MCF7 cell extracts was better than
      that of lungs and Hct116 cells. Cell extract made from GE-treated MCF-7 cells
      provided more efficient end-joining than from untreated and GSH-depleted cells.
      However, direct addition of GSH to the cell-free extracts showed considerable
      reduction in end-joining efficiency. Present data indicate that higher endogenous
      GSH favours rejoining of DNA DSBs (both restitution and illegitimate reunion)
      which in turn produce more exchange aberrations.

PMID- 27883911
TI  - Examining the relationship between rapid automatized naming and arithmetic
      fluency in Chinese kindergarten children.
AB  - Rapid automatized naming (RAN) has been found to predict mathematics. However,
      the nature of their relationship remains unclear. Thus, the purpose of this study
      was twofold: (a) to examine how RAN (numeric and non-numeric) predicts a
      subdomain of mathematics (arithmetic fluency) and (b) to examine what processing
      skills may account for the RAN-arithmetic fluency relationship. A total of 160
      third-year kindergarten Chinese children (83 boys and 77 girls, mean
      age=5.11years) were assessed on RAN (colors, objects, digits, and dice),
      nonverbal IQ, visual-verbal paired associate learning, phonological awareness,
      short-term memory, speed of processing, approximate number system acuity, and
      arithmetic fluency (addition and subtraction). The results indicated first that
      RAN was a significant correlate of arithmetic fluency and the correlations did
      not vary as a function of type of RAN or arithmetic fluency tasks. In addition,
      RAN continued to predict addition and subtraction fluency even after controlling
      for all other processing skills. Taken together, these findings challenge the
      existing theoretical accounts of the RAN-arithmetic fluency relationship and
      suggest that, similar to reading fluency, multiple processes underlie the RAN
      arithmetic fluency relationship.

PMID- 27883913
TI  - Water contamination with heavy metals and trace elements from Kilembe copper mine
      and tailing sites in Western Uganda; implications for domestic water quality.
AB  - The mining and processing of copper in Kilembe, Western Uganda, from 1956 to 1982
      left over 15 Mt of cupriferous and cobaltiferous pyrite dumped within a mountain
      river valley, in addition to mine water which is pumped to the land surface. This
      study was conducted to assess the sources and concentrations of heavy metals and
      trace elements in Kilembe mine catchment water. Multi-element analysis of trace
      elements from point sources and sinks was conducted which included mine tailings,
      mine water, mine leachate, Nyamwamba River water, public water sources and
      domestic water samples using ICP-MS. The study found that mean concentrations (mg
      kg-1) of Co (112), Cu (3320), Ni (131), As (8.6) in mine tailings were
      significantly higher than world average crust and were being eroded and
      discharged into water bodies within the catchment. Underground mine water and
      leachate contained higher mean concentrations (MUg L-1) of Cu (9470), Co (3430)
      and Ni (590) compared with background concentrations (MUg L-1) in un contaminated
      water of 1.9, 0.21 and 0.67 for Cu, Co and Ni respectively. Over 25% of household
      water samples exceeded UK drinking water thresholds for Al of 200 MUg L-1, Co
      exceeded Winsconsin (USA drinking) water thresholds of 40 MUg L-1 in 40% of
      samples while Fe in 42% of samples exceeded UK thresholds of 200 MUg L-1. The
      study however found that besides mining activities, natural processes of
      geological weathering also contributed to Al, Fe, and Mn water contamination in a
      number of public water sources.

PMID- 27883914
TI  - Association of outdoor air pollution and indoor renovation with early childhood
      ear infection in China.
AB  - BACKGROUND: Otitis media (OM) is a common infection in early childhood with
      repeated attacks that lead to long-term complications and sequelae, but its risk
      factors still remain unclear. OBJECTIVE: To examine the risk of childhood OM for
      different indoor and outdoor air pollutants during different timing windows, with
      a purpose to identify critical windows of exposure and key components of air
      pollution in the development of OM. METHODS: We conducted a retrospective cohort
      study of 1617 children aged 3-4 years in Changsha, China (2011-2012). Children's
      life-time prevalence of OM and exposure to indoor air pollution related to home
      renovation activities were surveyed by a questionnaire administered by the
      parents. Children's exposure to outdoor air pollution, including nitrogen dioxide
      (NO2), sulfur dioxide (SO2), and particulate matter with an aerodynamic diameter
      <= 10 MUm (PM10), was estimated using the measured concentrations at municipal
      monitoring stations. The odds ratio (OR) and 95% confidence interval (CI) of
      childhood OM for prenatal and postnatal exposure to indoor and outdoor air
      pollution were examined by using logistic regression model. RESULTS: Life-time
      prevalence of OM in preschool children (7.3%) was associated not only with
      prenatal exposure to industrial air pollutant with adjusted OR (95% CI) = 1.44
      (1.09-1.88) for a 27 MUg/m3 increase in SO2 but also with postnatal exposure to
      indoor renovations with OR (95% CI) = 1.62 (1.05-2.49) for new furniture and 1.81
      (1.12-2.91) for redecoration, particularly in girls. Combined exposure to outdoor
      SO2 and indoor renovation significantly increased OM risk. Furthermore, we found
      that exposure to outdoor SO2 and indoor renovation were significantly associated
      with the onset but not repeated attacks of OM. CONCLUSION: Prenatal exposure to
      outdoor industrial air pollution and postnatal exposure to indoor renovation are
      independently associated with early childhood OM in China and may cause the OM
      onset.

PMID- 27883912
TI  - Development of potential candidate reference materials for drugs in bottom
      sediment, cod and herring tissues.
AB  - Regular use of a reference material and participation in a proficiency testing
      program can improve the reliability of analytical data. This paper presents the
      preparation of candidate reference materials for the drugs metoprolol,
      propranolol, carbamazepine, naproxen, and acenocoumarol in freshwater bottom
      sediment and cod and herring tissues. These reference materials are not available
      commercially. Drugs (between 7 ng/g and 32 ng/g) were added to the samples, and
      the spiked samples were freeze-dried, pulverized, sieved, homogenized, bottled,
      and sterilized by gamma-irradiation to prepare the candidate materials.
      Procedures for extraction and liquid chromatography coupled with tandem mass
      spectrometry were developed to determine the drugs of interest in the studied
      material. Each target drug was quantified using two analytical procedures, and
      the results obtained from these two procedures were in good agreement with each
      other. Stability and homogeneity assessments were performed, and the relative
      uncertainties due to instability (for an expiration date of 12 months) and
      inhomogeneity were 10-25% and 4.0-6.8%, respectively. These procedures will be
      useful in the future production of reference materials.

PMID- 27883915
TI  - Novel mesoporous FeAl bimetal oxides for As(III) removal: Performance and
      mechanism.
AB  - In this study, novel mesoporous FeAl bimetal oxides were successfully
      synthesized, characterized, and employed for As(III) removal. Batch experiments
      were conducted to investigate the effects of Fe/Al molar ratio, dosage, and
      initial solution pH values on As(III) removal. The results showed that the FeAl
      bimetal oxide with Fe/Al molar ratio 4:1 (shorten as FeAl-4) can quickly remove
      As(III) from aqueous solution in a wide pH range. The FeAl-4 before and after
      reaction with As(III) was characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission
      electron microscopy (TEM), high-resolution transmission electron microscopy (HR
      TEM) and selected area electron diffraction (SAED), Brunauer-Emmett-Teller (BET)
      surface area measurement, and X-ray photoelectron spectroscopy (XPS). The BET
      results showed that the original FeAl-4 with a high surface area of 223.9 m2/g
      was a mesoporous material. XPS analysis indicated that the surface of FeAl-4
      possessed a high concentration of M-OH (where M represents Fe and Al), which was
      beneficial to the immobility of As(III). The excellent performance of FeAl-4
      makes it a potentially attractive material for As(III) removal from aqueous
      solution.

PMID- 27883917
TI  - Osmotic versus conventional membrane bioreactors integrated with reverse osmosis
      for water reuse: Biological stability, membrane fouling, and contaminant removal.
AB  - This study systematically compares the performance of osmotic membrane bioreactor
      - reverse osmosis (OMBR-RO) and conventional membrane bioreactor - reverse
      osmosis (MBR-RO) for advanced wastewater treatment and water reuse. Both systems
      achieved effective removal of bulk organic matter and nutrients, and almost
      complete removal of all 31 trace organic contaminants investigated. They both
      could produce high quality water suitable for recycling applications. During OMBR
      RO operation, salinity build-up in the bioreactor reduced the water flux and
      negatively impacted the system biological treatment by altering biomass
      characteristics and microbial community structure. In addition, the elevated
      salinity also increased soluble microbial products and extracellular polymeric
      substances in the mixed liquor, which induced fouling of the forward osmosis (FO)
      membrane. Nevertheless, microbial analysis indicated that salinity stress
      resulted in the development of halotolerant bacteria, consequently sustaining
      biodegradation in the OMBR system. By contrast, biological performance was
      relatively stable throughout conventional MBR-RO operation. Compared to
      conventional MBR-RO, the FO process effectively prevented foulants from
      permeating into the draw solution, thereby significantly reducing fouling of the
      downstream RO membrane in OMBR-RO operation. Accumulation of organic matter,
      including humic- and protein-like substances, as well as inorganic salts in the
      MBR effluent resulted in severe RO membrane fouling in conventional MBR-RO
      operation.

PMID- 27883918
TI  - Enhancement of bromate formation by pH depression during ozonation of bromide
      containing water in the presence of hydroxylamine.
AB  - This work investigated the fate of bromate formation during ozonation in the
      presence of hydroxylamine (HA). Results indicated that pH depression, as a
      commonly feasible control strategy for bromate formation during ozonation,
      unexpectedly enhanced the bromate formation during ozonation in the presence of
      HA. A dramatically high level of bromate was observed at acidic pH in the
      ozone/HA process. The scavenging experiments demonstrated the essential role of
      OH produced in the reaction of ozone with HA in bromate formation. In the
      process, OH mainly oxidizes bromide to Br, which is further oxidized by ozone and
      eventually converts to bromate. Further investigations suggested that the
      unexpected enhancement on bromate formation by pH depression can be mainly
      ascribed to the pH-dependent ozone decay, OH exposures and formation rate of Br.
      As pH decreased from 7 to 5, the reduced OH scavenging capacity of HA led to
      higher OH exposures, which contributed to the enhancement of bromate formation.
      As pH decreased from 5 to 3, the enhanced formation rate of Br largely augmented
      the formation of bromate. In addition, the ozone decay slowed down by pH
      depression provided more available ozone for the oxidation of the formed Br to
      bromate. The enhanced effect of pH depression on bromate formation was still
      observed in the real water samples in the ozone/HA process. Accordingly, pH
      depression might be avoided to control the bromate formation during ozonation in
      the presence of HA.

PMID- 27883916
TI  - Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic
      mice: A novel mechanism mediated by the activation of Nrf2.
AB  - Beta-amyloid (Abeta) plaques and oxidative stress are associated with the
      pathogenesis of Alzheimer's disease (AD). Hydrogen sulfide (H2S) has been
      recognized as a cytoprotectant, which improves learning memory impairment and
      exerts antioxidant effects in neurodegenerative disorders, including AD. The
      experiment was projected to explore the effects of H2S on cognitive deficits,
      Abeta levels and possible antioxidant mechanisms. Here, APP/PS1 transgenic mice
      were injected sodium hydrosulfide (NaHS, a H2S donor, 2.8mg/kg) once a day for
      three months. It was found that APP/PS1 transgenic mice exhibited cognitive
      deficits and a large number of senile plaques, along with neurons decrease and
      Abeta increase. However, intraperitoneal (i.p.) injection of NaHS improved
      learning memory deficits, decreased the number of senile plaques, Abeta1-40 and
      Abeta1-42 levels, suppressed neurons loss, together with up-regulated the levels
      of cystathionine-beta-synthase (CBS) and 3-mercaptopyruvate-sulfurtransferase
      (3MST). Furthermore, the protein levels of beta-amyloid precursor (APP) and beta
      secretase 1 (BACE1) were dramatically restrained after administration of H2S. In
      addition, H2S exerted antioxidant effects via up-regulation nuclear factor
      erythroid-2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and glutathione S
      transferase (GST). Taken together, these findings suggest that H2S ameliorates
      learning memory impairment, decreases the number of senile plaques in APP/PS1
      mice possibly through inhibition of Abeta production and activation of
      Nrf2/antioxidant response element (ARE) pathway.

PMID- 27883919
TI  - Bayesian belief network modelling of chlorine disinfection for human pathogenic
      viruses in municipal wastewater.
AB  - Chlorine disinfection of biologically treated wastewater is practiced in many
      locations prior to environmental discharge or beneficial reuse. The effectiveness
      of chlorine disinfection processes may be influenced by several factors, such as
      pH, temperature, ionic strength, organic carbon concentration, and suspended
      solids. We investigated the use of Bayesian multilayer perceptron (BMLP) models
      as efficient and practical tools for compiling and analysing free chlorine and
      monochloramine virus disinfection performance as a multivariate problem.
      Corresponding to their relative susceptibility, Adenovirus 2 was used to assess
      disinfection by monochloramine and Coxsackievirus B5 was used for free chlorine.
      A BMLP model was constructed to relate key disinfection conditions (CT, pH,
      turbidity) to observed Log Reduction Values (LRVs) for these viruses at constant
      temperature. The models proved to be valuable for incorporating uncertainty in
      the chlor(am)ination performance estimation and interpolating between operating
      conditions. Various types of queries could be performed with this model including
      the identification of target CT for a particular combination of LRV, pH and
      turbidity. Similarly, it was possible to derive achievable LRVs for combinations
      of CT, pH and turbidity. These queries yielded probability density functions for
      the target variable reflecting the uncertainty in the model parameters and
      variability of the input variables. The disinfection efficacy was greatly
      impacted by pH and to a lesser extent by turbidity for both types of
      disinfections. Non-linear relationships were observed between pH and target CT,
      and turbidity and target CT, with compound effects on target CT also evidenced.
      This work demonstrated that the use of BMLP models had considerable ability to
      improve the resolution and understanding of the multivariate relationships
      between operational parameters and disinfection outcomes for wastewater
      treatment.

PMID- 27883920
TI  - Nano-exploration of organic conditioning film formed on polymeric surfaces
      exposed to drinking water.
AB  - Adsorption of organic macromolecules onto surfaces in contact with waters forms a
      so-called conditioning film and induces modifications of the surface properties.
      Here, we characterized conditioning films formed onto two hydrophobic materials
      (used as pipe liner) and immersed for 24 h in tap water. Using combination of
      atomic force microscopy (AFM), and chemical force microscopy (CFM), we detected
      some changes in roughness and hydrophilic/hydrophobic balance of the surface of
      the tested coupons, and also the deposition of numerous organic polymers (few
      millions/cm2) randomly distributed on the surface. The maximum molecular
      extension of these organic polymers was in the range of 250-1250 nm according to
      the tested materials. Systematic analysis of the force curves with the
      theoretical models (WLC and FJC) allowed determining the proportion of rupture
      events related to the unfolding of both polysaccharide and polypeptide segments,
      which represented 75-80% and 20-25% of the analyzed curves, respectively. The
      number of autochthonous drinking water bacteria, which attached to the material
      within the same period of time was 10000-folds lower than the detected number of
      polymers attached to the surface. Even in drinking water systems with relatively
      low organic matter (dissolved organic carbon < 1.1 mg/L), the potential of
      formation of a conditioning biofilm is important.

PMID- 27883921
TI  - How well is microlitter purified from wastewater? - A detailed study on the
      stepwise removal of microlitter in a tertiary level wastewater treatment plant.
AB  - Wastewater treatment plants (WWTPs) can offer a solution to reduce the point
      source input of microlitter and microplastics into the environment. To evaluate
      the contributing processes for microlitter removal, the removal of microlitter
      from wastewater during different treatment steps of mechanical, chemical and
      biological treatment (activated sludge) and biologically active filter (BAF) in a
      large (population equivalent 800 000) advanced WWTP was examined. Most of the
      microlitter was removed already during the pre-treatment and activated sludge
      treatment further decreased the microlitter concentration. The overall retention
      capacity of studied WWTP was over 99% and was achieved after secondary treatment.
      However, despite of the high removal performance, even an advanced WWTP may
      constitute a considerable source of microlitter and microplastics into the
      aquatic environment given the large volumes of effluent discharged constantly.
      The microlitter content of excess sludge, dried sludge and reject water were also
      examined. According to the balance analyses, approximately 20% of the microlitter
      removed from the process is recycled back with the reject water, whereas 80% of
      the microlitter is contained in the dried sludge. The study also looked at easy
      microlitter sampling protocol with automated composite samplers for possible
      future monitoring purposes.

PMID- 27883922
TI  - Technical and environmental evaluation of an integrated scheme for the co
      treatment of wastewater and domestic organic waste in small communities.
AB  - A technical and environmental evaluation of an innovative scheme for the co
      treatment of domestic wastewater and domestic organic waste (DOW) was undertaken
      by coupling an upflow anaerobic sludge blanket (UASB), a sequencing batch reactor
      (SBR) and a fermentation reactor. Alternative treatment configurations were
      evaluated with different waste collection practices as well as various schemes
      for nitrogen and phosphorus removal. All treatment systems fulfilled the required
      quality of the treated effluent in terms of chemical oxygen demand (COD) and
      total suspended solids (TSS) concentrations. However, only the configurations
      performing the short-cut nitrification/denitrification with biological phosphorus
      removal met the specifications for water reuse. The environmental assessment
      included the analysis of impacts on climate change (CC), freshwater
      eutrophication (FE) and marine eutrophication (ME). A functional unit (FU) of
      2000 people receiving treatment services was considered. The most relevant
      sources of environmental impacts were associated to the concentration of
      dissolved methane in the UASB effluent that is emitted to the atmosphere in the
      SBR process (accounting for 41% of impacts in CC), electricity consumption,
      mainly for aeration in the SBR (representing 14% of the impacts produced in CC),
      and the discharge of the treated effluent in receiving waters (contributing 98%
      and 57% of impacts in FE and ME, respectively). The scheme of separate waste
      collection together with biological nitrogen removal and phosphorus uptake via
      nitrite was identified as the best configuration, with good treated effluent
      quality and environmental impacts lower than those of the other examined
      configurations.

PMID- 27883923
TI  - Gilles de la Tourette syndrome is associated with hypermethylation of the
      dopamine D2 receptor gene.
AB  - Several lines of evidence support a "dopaminergic hypothesis" in the
      pathophysiology of Gilles de la Tourette syndrome (TS). The aim of this study was
      to investigate for the first time epigenetic changes in DNA methylation in
      different dopamine genes in adult patients with TS. We included 51 well
      characterized adult patients with TS (41 males, 10 females, mean age = 35 +/-
      12.6 years, range, 18-71 years) and compared results with data from a group of 51
      sex- and age-matched healthy controls. Bisulfite sequencing was used to measure
      peripheral DNA methylation of the dopamine transporter (DAT), the dopamine D2
      receptor (DRD2), and the catechol-O-methyltransferase (COMT) genes. Compared to
      healthy controls, patients with TS showed significantly elevated methylation
      level of the DRD2 gene that positively correlated with tic severity. In contrast,
      DAT methylation was lower in more severely affected patients. Our results provide
      evidence for a role of altered epigenetic regulation of dopaminergic genes in the
      pathophysiology of TS. While DRD2 hypermethylation seems to be directly related
      to the neurobiology of TS that may lead to dopaminergic dysfunction resulting in
      enhanced thalamo-cortical movement-stimulating activity, DAT hypomethylation
      might reflect a secondary mechanism in order to compensate for increased
      dopaminergic signal transduction due to DRD2 hypermethylation. In addition, it
      can be speculated that spontaneous fluctuations of tics may be caused by short
      term alterations of methylation levels of dopaminergic genes resulting in dynamic
      changes of tonic/phasic dopaminergic signaling in the striatum and thalamo
      cortical output pathways.

PMID- 27883924
TI  - Physiological effects of epigallocatechin-3-gallate (EGCG) on energy expenditure
      for prospective fat oxidation in humans: A systematic review and meta-analysis.
AB  - Green tea catechins (GTCs) are known to improve fat oxidation (FOX) during
      fasted, rested and exercise conditions wherein epigallocatechin-3-gallate (EGCG)
      is thought to be the most pharmacologically active and has been studied
      extensively. From the available data of randomized controlled trials (RCTs) on
      EGCG, we carried out a systematic review and meta-analysis to elucidate whether
      EGCG consumption indeed increase energy expenditure (EE) and promote FOX. A
      systematic review of the literature was conducted using electronic databases
      (PubMed, Embase, Cochrane Library, CINAHL, JICST, JSTPLUS, and JMEDPLUS and
      others) and eight RCTs were included. RCTs were reviewed using Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines and
      methodological quality was assessed. After data extraction, results were
      aggregated using fixed- and random-effect approaches and expressed to quantify
      the relationship between the dose of EGCG for respiratory quotient (RQ), EE and
      rate of FOX to compare the EGCG and placebo treatments. The meta-analysis results
      of verities of studies in terms of dose and length of duration revealed that EGCG
      supplementation provided significant mean difference (MD) when compared with
      placebo for RQ [MD: -0.02; 95% confidence intervals (95% CI), -0.04 to 0.00;
      I2=67%; P=.01] and EE [MD: 158.05 kJ/day; 95% CI, 4.72 to 311.38; I2=0%; P=.04]
      in fixed-effect approach. Changes in FOX did not reach the level of statistical
      significance. Meta-analyses of EGCG influence on the body mass index, waist
      circumference and total body fat mass (TBFM) were also examined and their impact
      on the promotion of FOX is reported. Effect of EGCG doses was also systematically
      reviewed. Finding showed that EGCG intake moderately accelerates EE and reduces
      RQ. The analyses revealed that the EGCG resulted in difference in RQ and EE but
      the effect on the other measures of energy metabolism was relatively mild.
      Possibly, EGCG alone has the potential to increase metabolic rate at 300 mg dose.
      Collectively, the outcome supports the findings that EGCG has an effect on
      metabolic parameters. However, the large prospective trials are needed to confirm
      the findings.

PMID- 27883925
TI  - Factors associated with failure of oncology drugs in late-stage clinical
      development: A systematic review.
AB  - BACKGROUND: We aimed to describe the reasons for failure of experimental
      anticancer drugs in late-stage clinical development. MATERIAL AND METHODS: We
      searched the PharmaProjects database
      (https://citeline.com/products/pharmaprojects/) for anticancer drugs discontinued
      between 01/01/2009 and 06/30/2014. Drug programs that reached phase III trials,
      but never gained Food and Drug Administration (FDA) approval were compared to 37
      anti-cancer drugs achieving FDA approval in this time period. RESULTS: Forty-two
      drugs fit our criteria for development failures. These failed drugs (49%
      targeted, 23% cytotoxics, and 28% other) were tested in 43 cancer indications
      (drug programs). Only 16% (7/43) of failed drug programs adopted a biomarker
      driven rationale for patient selection versus 57% (21/37) of successful drug
      programs (P<0.001). Phase II trial information was available in 32 of 43 failed
      drug programs and in 32 of 37 successful programs. Nine of the 32 trials (28%) of
      failed drugs versus 28 of 32 trials (87%) of successful drugs (P<0.001) achieved
      proof of concept (single agent response rate (RR) ?20% or combination therapy
      showing a ?20% RR increase above the median historical RR without the
      experimental agent (with a minimal absolute increase of 5%) or a randomized phase
      II trial showing significance (P?0.05) for its primary outcome). No pattern of
      study sites, trial design or funding characteristics emerged from the failed drug
      analysis. CONCLUSION: For drugs that reached Phase III, lack of a biomarker
      driven strategy and failure to attain proof of concept in phase II are potential
      risk factors for later discontinuation, especially for targeted agents.

PMID- 27883926
TI  - Application of genetically engineered Salmonella typhimurium for interferon-gamma
      induced therapy against melanoma.
AB  - Salmonella have been experimentally used as anti-cancer agents, because they show
      selective growth in tumours. In this study, we genetically modified attenuated
      Salmonella typhimurium to express and secrete interferon-gamma (IFN-gamma) as a
      tumouricidal agent to enhance the therapeutic efficacy of Salmonella. IFN-gamma
      was fused to the N-terminal region (residues 1-160) of SipB (SipB160) for
      secretion from bacterial cells. Attenuated S. typhimurium expressing recombinant
      IFN-gamma (S. typhimurium (IFN-gamma)) invaded the melanoma cells and induced
      cytotoxicity. Subcutaneous administration of S. typhimurium (IFN-gamma) also
      efficiently inhibited tumour growth and prolonged the survival of C57BL/6 mice
      bearing B16F10 melanoma compared with administration of phosphate-buffered saline
      (PBS), unmodified S. typhimurium or S. typhimurium expressing empty vector (S.
      typhimurium [Vec]) in a natural killer (NK) cell-dependent manner. Moreover,
      genetically modified Salmonella, including S. typhimurium (IFN-gamma), showed
      little toxicity to normal tissues with no observable adverse effects. However, S.
      typhimurium (IFN-gamma)-mediated tumour suppression was attributed to direct
      killing of tumour cells rather than to stable anti-tumour immunity. Collectively,
      these results suggest that tumour-targeted therapy using S. typhimurium (IFN
      gamma) has potential for melanoma treatment.

PMID- 27883928
TI  - Graduate entry nurses' initial perspectives on nursing: Content analysis of open
      ended survey questions.
AB  - BACKGROUND: Graduate entry nursing courses offer individuals with prior degrees
      the opportunity to gain nursing qualifications and facilitate career change.
      While it is known that accelerated graduate entry courses are increasingly
      popular, the perceptions of nursing held by such individuals and the influence
      this has on those seeking to enter the profession are less clearly understood.
      OBJECTIVE: To explore graduate entry nursing students' perceptions of nursing on
      entering their pre-registration course. DESIGN: A descriptive design utilising
      cross-section survey with two open-ended questions: What do you believe the role
      of the nurse is? What things have influenced that view? were asked. Demographic
      data were analysed using descriptive frequencies, while the two open-ended
      questions were analysed using summative content analysis. SETTING: One university
      based postgraduate graduate entry nursing course in Australia PARTICIPANTS: Eight
      cohorts (n=286) commencing students with prior degrees other than nursing.
      RESULTS: The course attracts students from diverse backgrounds. Exposure to
      nursing and nurses, either as a consumer of health care or other health care
      role, plays a primary role in influencing career change. However, similar to
      those found with school leavers, there remains much misinformation about nurses'
      roles for students in these courses. Most identify the role of caring in nursing.
      For some, media representations are the only information sources. DISCUSSION:
      Graduate entry courses offer opportunities to attract new nurses and contribute
      to addressing workforce shortages. However, there is still a lack of knowledge of
      nursing roles among students on entry. More work is required by the profession to
      ensure nursing is accurately and positively represented to the community.

PMID- 27883927
TI  - Randomized pilot trial of a cognitive-behavioral alcohol, self-harm, and HIV
      prevention program for teens in mental health treatment.
AB  - Adolescents with mental health conditions represent a high-risk group for
      substance use, deliberate self-harm (DSH), and risky sexual behavior. Mental
      health treatment does not uniformly decrease these risks. Effective prevention
      efforts are needed to offset the developmental trajectory from mental health
      problems to these behaviors. This study tested an adjunctive cognitive-behavioral
      family-based alcohol, DSH, and HIV prevention program (ASH-P) for adolescents in
      mental healthcare. A two group randomized design was used to compare ASH-P to an
      assessment only control (AO-C). Participants included 81 adolescents and a
      parent. Assessments were completed at pre-intervention as well as 1, 6, and 12
      months post-enrollment, and included measures of family-based mechanisms and high
      risk behaviors. ASH-P relative to AO-C was associated with greater improvements
      in most family process variables (perceptions of communication and parental
      disapproval of alcohol use and sexual behavior) as well as less DSH and greater
      refusal of sex to avoid a sexually transmitted infection. It also had a moderate
      (but non-significant) effect on odds of binge drinking. No differences were found
      in suicidal ideation, alcohol use, or sexual intercourse. ASH-P showed initial
      promise in preventing multiple high-risk behaviors. Further testing of prevention
      protocols that target multiple high-risk behaviors in clinical samples is
      warranted.

PMID- 27883929
TI  - Happy to help/happy to be here: Identifying components of successful clinical
      placements for undergraduate nursing students.
AB  - INTRODUCTION: The clinical placement learning environment is a critical component
      of nursing education where Australian nursing students spend a minimum of 800h.
      Identifying components of successful clinical placements for undergraduate
      nursing students is therefore paramount. PURPOSE: To assess nursing students'
      views of the learning environment during clinical placement with an emphasis on
      the pedagogical atmosphere, leadership style of the ward manager, and premises of
      nursing on the unit or ward. MATERIAL AND METHODS: The study used Clinical
      Learning Environment, Supervision and nurse teacher (CLES+T) questionnaire to
      examine 150 final year undergraduate students' perceptions of the clinical
      placement learning environment. The questionnaire was anonymous and completed by
      the students at the end of their clinical placement. The statistical program SPSS
      v22 was used. Principal components analysis (PCA) for data reduction was run on
      the 42-question section of the first dimension ('pedagogical atmosphere on the
      ward') of the questionnaire that measured the perceptions of the learning
      environment of the clinical placement of the 150 final-year undergraduate nursing
      students. The comments sections of the factors were subjected to interpretive
      content analysis to create the themes for the two components. RESULTS: Principle
      Component Analysis revealed two components that had eigenvalues greater than one:
      'Happy to Help' Component 1 and 'Happy to be Here' Component 2. These components
      were statistically significant (p<0.0005), using Bartlett's Test of Sphericity
      indicating that the data was likely factorizable. These components scored higher
      than any other related factors. CONCLUSIONS: Student nurses value a welcoming
      workplace where staff and educators are happy to help and have a positive
      attitude to student presence on the wards. More than any other factors these ward
      based factors appear to have the strongest influence on student satisfaction.

PMID- 27883930
TI  - Reconciling community-based Indigenous research and academic practices: Knowing
      principles is not always enough.
AB  - Historically, Indigenous health research in Canada has failed to engage
      Indigenous peoples and communities as primary stakeholders of research evidence.
      Increasingly, research ethics and methodologies are being positioned as tools for
      Indigenous self-determination. In response, mainstream institutions have
      developed new ethical principles for research involving Indigenous people. While
      these transformations are necessary steps towards re-orienting research
      practices, they are not prescriptive. In this paper, we make visible three
      dilemmas from a case study in which Indigenous health research frameworks
      provided limited guidance or were unclear about how to balance community
      priorities with Indigenous research principles. We also discuss the strategies
      used to resolve each of these dilemmas. We draw examples from a project that
      examined the lived experiences of children and youth living with FASD and their
      caregivers. This project was conducted in collaboration with Sheshatshiu Innu
      First Nation, an Indigenous community in Labrador, Canada. In doing so, we argue
      that knowing the key guiding principles in Indigenous health research is not
      always enough, and that the 'real-world' context of practices and relationships
      can lead to conflicts that are not easily resolved with adherence to these
      principles.

PMID- 27883931
TI  - Disassembly of amphiphilic small molecular prodrug with fluorescence switch
      induced by pH and folic acid receptors for targeted delivery and controlled
      release.
AB  - We develop a new type of pH-responsive amphiphilic small molecular prodrug by
      conjugating folic acid with anti-tumour doxorubicin via a hydrazone bond. This
      prodrug is featured by high and precise drug loading (55.4wt%), which can self
      assemble into micellar nanoparticles in neutral environment while disassemble in
      the presence of tumour cells expressing folic acid receptors or the acidic
      tumoral endosomal environment. The prodrug nanoparticles can effectively improve
      anticancer efficacy due to the features of pH-triggered drug release and targeted
      delivery. Moreover, in vitro cell study further indicated that the resulting
      prodrug nanoparticles had enhanced cytotoxicity for folic-acid-positive cells
      (HeLa) compared to folic-acid-negative cells (MCF-7). More importantly, the
      induced disassembly of prodrug nanoparticles can "switch on" the inherent
      fluorescence of the internalized doxorubicin drug in the tumour microenvironment,
      which can be used for the detection of tumour cells. We believe that this
      strategy can pave a new way for designing small molecular drug delivery systems
      and facilitate tumour diagnosis and treatment simultaneously.

PMID- 27883932
TI  - Biological response of human suture mesenchymal cells to Titania nanotube-based
      implants for advanced craniosynostosis therapy.
AB  - Titania nanotubes (TNTs) engineered on titanium (Ti) surfaces (i.e. TNT/Ti) and
      loaded with specific drugs have been recognised as a promising solution for
      localised therapeutic delivery to address several medical problems not feasible
      with conventional drug administration. We propose the use of TNT/Ti protein
      releasing implants to treat paediatric craniofacial abnormality in
      craniosynostosis caused by premature fusion of cranial sutures. In this study, we
      have analysed the biological response of human suture mesenchymal cells (SMCs),
      extracted from two different patients undergoing craniofacial reconstruction
      surgery, at the TNT/Ti implant surface. The experimental groups included large
      diameter TNT/Ti implants, with and without biopolymer surface coating (Chitosan
      and Pluronic-F127) while the controls comprised of flat Ti disc and tissue
      culture plastic. The non-loaded implant surfaces and the cellular interactions at
      the implant-cell interface were characterised using scanning electron microscopy
      (SEM). The SMC adhesion, viability and proliferation were determined by MTT assay
      and manual cell counting at day 1 and day 3 of cell incubation. SEM showed
      significant reduction in initial attachment and adhesion of SMCs at TNT-cell
      biointerface compared with the control Ti discs. Subsequent cell proliferation
      results also revealed a decrease in the number of viable cells on the TNT
      surfaces. The nanotopography and structural features along with the surface
      chemistry dictated the cellular response, with nanotubular surfaces (with and
      without polymer coating) impeding cell adhesion and proliferation. Our findings
      hold promise for the use of TNT-based cranial implants as a delivery system to
      prevent sutural bone growth for advanced craniosynostosis therapy.

PMID- 27883933
TI  - Microbiome, metabolites and host immunity.
AB  - In the intestine, the microbial genomes and repertoire of biochemical reactions
      outnumber those of the host and significantly contribute to many aspects of the
      host's health, including metabolism, immunity, development and behavior, while
      microbial community imbalance is associated with disease. The crosstalk between
      the host and its microbiome occurs in part through the secretion of metabolites,
      which have a profound effect on host physiology. The immune system constantly
      scans the intestinal microenvironment for information regarding the metabolic
      state of the microbiota as well as the colonization status. Recent studies have
      uncovered a major role for microbial metabolites in the regulation of the immune
      system. In this review, we summarize the central findings of how microbiota
      modulated metabolites control immune development and activity.

PMID- 27883934
TI  - The application of half-life in clinical decision making: Comparison of the
      pharmacokinetics of extended-release topiramate (USL255) and immediate-release
      topiramate.
AB  - OBJECTIVE: For extended-release drugs with multi-compartment kinetics, such as
      topiramate, effective half-life (t1/2eff) may be a more clinically relevant
      parameter than elimination half-life (t1/2z). Using topiramate as a real-life
      example, the objective was to compare these half-life values for immediate- and
      extended-release topiramate (TPM-IR and USL255, respectively) to understand how
      drug pharmacokinetics may impact drug dosing recommendations. METHODS: The t1/2z
      and t1/2eff for USL255 and TPM-IR were compared using data from a phase I study
      (N=36) of 200mg USL255 administered once daily (QD) or TPM-IR twice daily (BID);
      effect of sampling duration on t1/2z was investigated. To further explore the
      relationship between half-life and dosing, steady-state PK was simulated for
      USL255 and TPM-IR. RESULTS: As previously reported, mean t1/2z was similar
      between USL255 (80.2h) and TPM-IR (82.8h); TPM-IR t1/2z was ~4 times longer than
      reported in the Topamax label (21h). In contrast, USL255 displayed a 1.5 fold
      longer t1/2eff (55.7 vs 37.1h for TPM-IR). When t1/2z was calculated from 48 to
      336h, values ranged from 28.8 to 82.8h. Simulated steady-state PK profiles of
      USL255 QD exhibited reduced plasma fluctuations during a dosing interval vs TPM
      IR QD or BID. SIGNIFICANCE: As expected for the same moiety, t1/2z of USL255 and
      TPM-IR were similar; however, the longer t1/2eff for USL255 better approximates
      differences in recommend dosing (QD USL255 vs BID TPM-IR). Further, sampling
      duration impacted t1/2z, diminishing its predictive value for determining dose
      regimens; sampling-time differences may also explain t1/2z discrepancy between
      TPM-IR here versus Topamax label. As expected, steady-state simulations confirm
      that although TPM-IR has a long t1/2z, taking TPM-IR QD would lead to large
      plasma fluctuations. These data demonstrate that t1/2z may be less clinically
      meaningful than t1/2eff, and using t1/2z for some drugs may lead to erroneous
      conclusions regarding dosing regimens.

PMID- 27883935
TI  - Liquid fructose in Western-diet-fed mice impairs liver insulin signaling and
      causes cholesterol and triglyceride loading without changing calorie intake and
      body weight.
AB  - BACKGROUND/OBJECTIVES: Liquid fructose associates with prevalence of type 2
      diabetes mellitus and obesity. Intervention studies suggest that metabolically
      unfit individuals are more responsive than healthy individuals to liquid
      fructose. We determined whether mice consuming an obesogenic Western diet were
      more responsive than chow-fed mice to the alterations induced by liquid fructose
      supplementation (LFS). METHODS: C57BL/6N mice were fed chow or Western diet+/-ad
      libitum 15% fructose solution for 12 weeks. Food and liquid intake and body
      weight were monitored. Plasma analytes and liver lipids, histology and the
      expression of genes related to lipid handling, endoplasmic reticulum stress,
      inflammation and insulin signaling were analyzed. RESULTS: Western diet increased
      energy intake, visceral adipose tissue (vWAT), body weight, plasma and liver
      triglycerides and cholesterol, and inflammatory markers in vWAT vs. chow-fed
      mice. LFS did not change energy intake, vWAT or body weight. LFS significantly
      increased plasma and liver triglycerides and cholesterol levels only in Western
      diet-fed mice. These changes associated with a potentiation of the increased
      liver expression of PPARgamma and CD36 that was observed in Western-fed mice and
      related to the increased liver mTOR phosphorylation induced by LFS. Furthermore,
      LFS in Western-diet-fed mice induced the largest reduction in liver IRS2 protein
      and a significant decrease in whole-body insulin sensitivity. CONCLUSIONS: LFS in
      mice, in a background of an unhealthy diet that already induces fatty liver
      visceral fat accretion and obesity, increases liver lipid burden, hinders hepatic
      insulin signaling and diminishes whole-body insulin sensitivity without changing
      energy intake.

PMID- 27883936
TI  - Relationship between FGF21 and UCP1 levels under time-restricted feeding and high
      fat diet.
AB  - Fibroblast growth factor 21 (FGF21) exhibits a circadian oscillation, and its
      induction is critical during fasting. When secreted by liver and skeletal muscle,
      FGF21 enhances thermogenic activity in brown adipose tissue (BAT) by utilizing
      uncoupling protein 1 (UCP1) to dissipate energy as heat. Recently, it has been
      reported that UCP1 is not required for FGF21-mediated reduction in body weight or
      improvements in glucose homeostasis. As the relationship between FGF21 and UCP1
      induction in tissues other than BAT is less clear, we tested the effect of
      restricted feeding (RF) and high dietary fat on FGF21 circadian expression and
      its correlation with UCP1 expression in liver and white adipose tissue (WAT).
      High dietary fat disrupted Fgf21 mRNA circadian oscillation but increased its
      levels in WAT. RF led to increased liver FGF21 protein levels, whereas those of
      UCP1 decreased. In contrast, WAT FGF21 protein levels increased under high-fat
      diet, whereas those of UCP1 decreased under RF. In summary, FGF21 exhibits
      circadian oscillation, which is disrupted with increased dietary fat. The
      relationship between FGF21 and UCP1 levels depends on the tissue and the cellular
      energy status.

PMID- 27883937
TI  - Atorvastatin protected from paraquat-induced cytotoxicity in alveolar macrophages
      via down-regulation of TLR-4.
AB  - The current study designed to clarify the mechanism of paraquat-induced
      cytotoxicity and protective effects of Atorvastatin on freshly isolated alveolar
      macrophages (AMs). AMs were collected via bronchoalveolar lavage and exposed to
      various concentrations of paraquat in the presence and absence of atorvastatin
      for 24h. Cell viability, myeloperoxidase activity; nitric oxide generation and
      total antioxidant capacity were assessed. Expression of TLR-4 at mRNA and protein
      levels were studied by using PCR and western blot methods Atorvastatin enhanced
      the paraquat-reduced cell viability and reduced the paraquat-induced
      myeloperoxidase activity and nitric oxide production. Moreover, atorvastatin down
      regulated by 60% the paraquat up-regulated expression of TLR-4 at protein and
      mRNA level. Our results suggest that, AMs in vitro model could be a novel
      cytological tool for studies on paraquat poisoning and therapy regimens.
      Additionally, atorvastatin cytoprotective effects on paraquat-induced
      cytotoxicity partly attribute to its anti-myeloperoxidase, antioxidant
      properties, which might be regulated via TLR-4 expression.

PMID- 27883939
TI  - Is enhanced biodiversity protection conflicting with ambitious bioenergy targets
      in eastern Finland?
AB  - The study describes how qualitative stakeholder feedback can be used in
      quantitative scenarios to simulate forest resource use under alternative
      management objectives. In earlier studies in the region of eastern Finland,
      stakeholders did not see a possible conflict between increased bioenergy use and
      nature conservation; this finding is contrary to the results of other studies.
      The aim of this study was to test with a quantitative modelling approach whether
      the stakeholder expectation holds and whether forest management in eastern
      Finland can simultaneously increase biomass utilization and biodiversity
      protection. Prior to this study, three alternative scenarios on forest resource
      use were created in a participatory stakeholder process, involving a broad range
      of stakeholders, with half of them being from research and education. In the
      current study, a large-scale forest resource planning model (MELA) and a
      sustainability impact assessment tool (ToSIA) were used to simulate the different
      alternative scenarios and present the results back to the stakeholders in order
      to evaluate them. The scenarios were evaluated by stakeholders using multi
      criteria analysis. In a survey, the stakeholders indicated that biodiversity,
      employment, recreational value and greenhouse gas emissions were the most
      important indicators to them, whereas growing stock, amount of harvested
      roundwood, energy wood and protected forest area were considered less important.
      Of the created scenarios, the scenario combining bioenergy and biodiversity
      targets was the most preferred by the stakeholders as it performed well on those
      indicators that were identified by stakeholders as the most important. In this
      scenario, the area of protected forest and bioenergy production were increased
      simultaneously. With this study we offer a framework for evaluating different
      alternatives for future land use. The framework helps to identify key issues that
      are important to the stakeholders so that they can be taken into consideration in
      future land-use planning. In addition, the results confirm the stakeholder
      expectation that by protecting more forests while simultaneously increasing the
      mobilization of potentially available wood resources, both targets can be met
      without compromising too much other forest functions such as timber production
      and recreation.

PMID- 27883938
TI  - Pretreatment of activated human CD8 T cells with IL-12 leads to enhanced TCR
      induced signaling and cytokine production.
AB  - During the immune response to pathogens and autoantigens, CD8T cells are exposed
      to numerous inflammatory agents including the cytokine IL-12. Previous studies
      have focused on how IL-12 regulates T cell functions when present during or after
      the activation of the T cell receptor (TCR). However, recent studies suggest that
      prior exposure to IL-12 also alters the TCR responsiveness of murine T cells.
      Whether similar phenomena occur in human activated CD8T cells and the mechanisms
      mediating these effects remain unexplored. In this study, we observed that
      pretreatment of human activated CD8T cells with IL-12 results in increased
      cytokine mRNA and protein production following subsequent TCR challenge. The
      potentiation of TCR-mediated cytokine release was transient and required low
      doses of IL-12 for at least 24h. Mechanistically, prior exposure to IL-12
      increased the TCR induced activation of select MAPKs and AKT without altering the
      activation of more proximal TCR signaling molecules, suggesting that the IL-12
      mediated changes in TCR signaling are responsible for the increased production of
      cytokines. Our data suggest that prior treatment with IL-12 potentiates human
      CD8T cell responses at sites of infection and inflammation, expanding our
      understanding of the function of this clinically important cytokine.

PMID- 27883940
TI  - Descriptive and multivariate analyses of four Tunisian wastewater treatment
      plants: A comparison between different treatment processes and their efficiency
      improvement.
AB  - This study was undertaken to evaluate the performance of four wastewater
      treatment plants/processes over a 4 year period. The wastewater flow evolution,
      energy consumption, and quality indicator parameters (BOD5, COD and TSS) at the
      inlet and outlet sites of the plants were determined. In comparing three domestic
      WWTPs with different wastewater treatment processes, the multivariate analyses
      (RDA and ANOVA) showed that although the Agareb plant received the highest
      pollution load, it displayed a high level of removal efficiency especially for
      COD, BOD, TSS, TKN and NH4+. It also revealed that the fluctuations in the
      wastewater composition and its contamination by varied industrial discharge could
      lead to the decrease in performance of the WWTP with activated sludge process as
      observed for the Southern Sfax plant. However, the electrolysis of the outlet
      water of Southern Sfax plant showed a significant improvement in COD removal.

PMID- 27883941
TI  - Smallholder farmers' behavioural intentions towards sustainable agricultural
      practices.
AB  - The introduction of sustainable practices is considered a win-win strategy for
      low-income countries because of its potential to simultaneously improve food
      security and address environmental issues. Despite the numerous studies that
      focus on the adoption of technological innovations, little work has been done on
      the socio-psychological behaviour of farmers with regard to sustainable
      practices. This study investigates smallholder farmers' intentions towards two
      practices: minimum tillage and row planting. The decomposed theory of planned
      behaviour is used as a theoretical framework to analyse the intentions. The
      findings reveal that attitudes and normative issues positively explain farmers'
      intentions to adopt both practices. Perceived control also has a positive
      significant effect on the intention to apply minimum tillage. When the intention
      is formed, farmers are expected to carry out their intention when opportunities
      arise. Moreover, perceived usefulness, social capital, and perceived ease of
      operation are also significant predictors of farmers' attitudes. Furthermore,
      social capital and training are factors that positively affect the normative
      issue, which in turn also positively mediates the relationship between training,
      social capital and intention. Finally, it is shown that neither the perceived
      resources nor information from the media significantly affect farmers'
      intentions. This paper thus confirms that social capital, personal efficacy,
      training and perceived usefulness play significant roles in the decision to adopt
      sustainable practices. In addition, willingness to adopt seems to be limited by
      negative attitudes and by weak normative issues. Therefore, to improve adoption
      of sustainable practices by smallholder farmers, attention should be given to
      socio-psychological issues. This could lead to improvements in farm productivity
      and enhance the livelihoods of smallholders.

PMID- 27883943
TI  - Targeted therapy for breast cancer and molecular mechanisms of resistance to
      treatment.
AB  - In recent years, clinical trials investigating new drugs and therapeutic
      combinations have led to promising advances in breast cancer therapy. Subtyping
      breast cancers into hormone receptor (HR) positive, epidermal growth factor
      receptor (HER2) positive, and triple negative breast cancer (TNBC) is currently
      the basis of diagnosing and treating this disease. In addition to endocrine and
      HER2-targeted therapies in their respective subtypes, evidence from recent
      preclinical studies have shown several targetable pathways that overcome
      resistance in the clinical setting. The mTOR inhibitor everolimus and the CDK4/6
      inhibitor palbociclib have been approved in HR-positive metastatic breast cancer
      (MBC) due to improved disease-free survival (DFS). Adding pertuzumab to
      trastuzumab in combination with taxanes further improves DFS in HER2-positive
      breast cancer. Targeted therapy to the heterogeneous group of TNBC is needed in
      combination with chemotherapy. However, patient selection and predictive
      biomarker development remains a big challenge for targeted therapy development in
      TNBC.

PMID- 27883942
TI  - Dye degradation by green heterogeneous Fenton catalysts prepared in presence of
      Camellia sinensis.
AB  - This work describes the synthesis and characterization of supported green iron
      catalysts, prepared with Camellia sinensis tea extract, and their application in
      heterogeneous Fenton degradation of pollutant dyes. The influence of the catalyst
      synthesis conditions in the iron and organic content were investigated by X-ray
      fluorescence and thermogravimetric analyses. Irregular, chain-like nanoparticles,
      in the size range of 20-100 nm, capped by polyphenolic natural compounds, were
      visualized by TEM micrographs. TEM-EDS revealed a high iron content in the
      nanoparticles as well as a high carbon content all over the catalyst surface,
      indicating the coverage by the polyphenolic compounds of the tea. X-ray powder
      diffraction revealed the amorphous nature of the nanoparticles, tentatively
      ascribed to iron(II)/(III) oxides and oxohydroxides composites. The Fenton
      degradation of different dyes was successfully accomplished, leading to complete
      decolourization in less than 3 h of reaction. Influence of hydrogen peroxide
      concentration, catalyst dosage, pH, temperature and catalyst support, were
      investigated. The catalysts prepared with black tea over silica furnished the
      higher iron contents and were the most actives for dye degradation.

PMID- 27883944
TI  - Allocative and implementation efficiency in HIV prevention and treatment for
      people who inject drugs.
AB  - BACKGROUND: Estimated global new HIV infections among people who inject drugs
      (PWID) remained stable over the 2010-2015 period and the target of a 50%
      reduction over this period was missed. To achieve the 2020 UNAIDS target of
      reducing adult HIV infections by 75% compared to 2010, accelerated action in
      scaling up HIV programs for PWID is required. In a context of diminishing
      external support to HIV programs in countries where most HIV-affected PWID live,
      it is essential that available resources are allocated and used as efficiently as
      possible. METHODS: Allocative and implementation efficiency analysis methods were
      applied. Optima, a dynamic, population-based HIV model with an integrated program
      and economic analysis framework was applied in eight countries in Eastern Europe
      and Central Asia (EECA). Mathematical analyses established optimized allocations
      of resources. An implementation efficiency analysis focused on examining
      technical efficiency, unit costs, and heterogeneity of service delivery models
      and practices. RESULTS: Findings from the latest reported data revealed that
      countries allocated between 4% (Bulgaria) and 40% (Georgia) of total HIV
      resources to programs targeting PWID - with a median of 13% for the eight
      countries. When distributing the same amount of HIV funding optimally, between 9%
      and 25% of available HIV resources would be allocated to PWID programs with a
      median allocation of 16% and, in addition, antiretroviral therapy would be scaled
      up including for PWID. As a result of optimized allocations, new HIV infections
      are projected to decline by 3-28% and AIDS-related deaths by 7-53% in the eight
      countries. Implementation efficiencies identified involve potential reductions in
      drug procurement costs, service delivery models, and practices and scale of
      service delivery influencing cost and outcome. A high level of implementation
      efficiency was associated with high volumes of PWID clients accessing a drug harm
      reduction facility. CONCLUSION: A combination of optimized allocation of
      resources, improved implementation efficiency and increased investment of non-HIV
      resources is required to enhance coverage and improve outcomes of programs for
      PWID. Increasing efficiency of HIV programs for PWID is a key step towards
      avoiding implicit rationing and ensuring transparent allocation of resources
      where and how they would have the largest impact on the health of PWID, and
      thereby ensuring that funding spent on PWID becomes a global best buy in public
      health.

PMID- 27883945
TI  - Recent advances in the treatment of lower-risk non-del(5q) myelodysplastic
      syndromes (MDS).
AB  - Patients with lower-risk myelodysplastic syndromes (MDS) are affected primarily
      by symptoms of chronic anemia and fatigue rather than progression to acute
      myeloid leukemia. Severe thrombocytopenia, although less common in lower-risk
      MDS, is associated with increased risk of bleeding. For anemic patients, the
      principal aim of treatment is to improve anemia and decrease red blood cell
      transfusions. For transfusion-dependent patients with lower-risk MDS without
      chromosome 5q deletion [non-del(5q) MDS], there are limited effective treatments.
      Erythropoiesis-stimulating agents (ESAs) are generally first-line therapy,
      yielding frequent responses with a median duration of 18-24 months.
      Immunosuppressive therapy or allogeneic stem cell transplantation are restricted
      to select patients. New strategies for ESA-refractory or relapsed patients
      include lenalidomide, alone or in combination with ESAs; oral azacitidine; and
      new molecules such as the activin receptor type II ligand traps luspatercept and
      sotatercept. In thrombocytopenic patients, thrombopoietin receptor agonists are
      under evaluation. While trials to evaluate these treatment strategies are
      underway, efforts are needed to optimize therapies through better patient
      selection and response prediction as well as integrating molecular and genetic
      data into clinical practice. We provide an overview of current treatment
      approaches for lower-risk non-del(5q) MDS and explore promising directions for
      future research.

PMID- 27883946
TI  - Pattern and risk of developing alcohol use disorders, illegal substance use and
      psychiatric disorders after early onset of alcohol use: Results of the Thai
      National Mental Health Survey 2013.
AB  - INTRODUCTION: Although underage drinking is a global concern, little is known
      about the relationship between age at first drink and development of various
      psychiatric comorbidities. METHODS: A secondary data analysis was done among 2928
      lifetime drinkers from the Thai National Mental Health Survey 2013. Age at first
      drink, and onset of related psychiatric outcomes were inquired. Survival analysis
      using Cox regression was performed to estimate the risk over time for psychiatric
      problems across age ranges at first drink. RESULTS: Two-thirds of male and one
      third of female drinkers were considered underage at drinking onset. Substance
      use and abuse developed earlier (<5 years) than alcohol use disorders (AUDs) and
      other outcomes (mostly >10 years). Those who started drinking before age 15 years
      were more likely to develop use of cannabis (HR=4.75; 95% CI 2.73, 8.24), club
      drugs (HR=2.88; 95% CI 1.46, 5.71) and inhalants (HR=6.46; 95% CI% 1.64, 25.37),
      compared to those who were 20 years or older at drinking onset. Using age as an
      alternative time-scale, those aged <15years at drinking onset were significantly
      more likely to experience AUDs, psychotic symptoms, intermittent explosive
      disorder and panic disorder. However, the early onset drinkers were less likely
      to develop depression compared to those who started at age 20 years and over.
      CONCLUSION: Premature alcohol consumption tends to be a gateway to various
      serious consequences. Efforts of such drinking age policy and interventions are
      needed to address vulnerable young populations.

PMID- 27883947
TI  - Social cognitive predictors of treatment outcome in cannabis dependence.
AB  - BACKGROUND: Drug-related outcomes expectancies and refusal self-efficacy are core
      components of Social Cognitive Theory. Both predict treatment outcome in alcohol
      use disorders. Few studies have reported expectancies and refusal self-efficacy
      in cannabis dependence. None have examined both, although both constructs are key
      targets in Cognitive-Behavioural Therapy (CBT). This study tests the predictive
      role of expectancies and refusal self-efficacy in treatment outcome for cannabis
      dependence. DESIGN: Outpatients completed a comprehensive assessment when
      commencing cannabis treatment and predictors of treatment outcome were tested.
      SETTING: A university hospital alcohol and drug outpatient clinic. PARTICIPANTS:
      221 cannabis-dependent patients participated in a 6-week CBT program where the
      goal was abstinence. MEASUREMENTS: Cannabis Expectancy Questionnaire and Cannabis
      Refusal Self-Efficacy Questionnaire, cannabis dependence severity [Severity of
      Dependence Scale], psychological distress [General Health Questionnaire] at
      baseline; the timeline follow-back procedure at baseline and each session.
      FINDINGS: Patients reporting lower confidence in their ability to resist cannabis
      during high negative affect (emotional relief refusal self-efficacy) had a lower
      likelihood of abstinence (p=0.004), more days of use (p<0.001), and larger amount
      used (p<0.001). Negative cannabis expectancies predicted greater likelihood of
      abstinence (p=0.024). Higher positive expectancies were associated with lower
      emotional relief self-efficacy, mediating its association with outcome (p<0.001).
      CONCLUSIONS: Emotional relief refusal self-efficacy and negative expectancies are
      predictive of better treatment outcomes for cannabis dependence. Positive
      expectancies may indirectly predict poorer outcome because of a negative
      association with self-efficacy, but this conclusion remains tentative as
      directionality could not be established.

PMID- 27883948
TI  - Prevalence, sociodemographic correlates and DSM-5 substance use disorders and
      other psychiatric disorders among sexual minorities in the United States.
AB  - PURPOSE: The purpose of this study was to present current nationally
      representative data on the prevalences, sociodemographic correlates and risk of
      DSM-5 substance use disorders and other psychiatric disorders among sexual
      minorities (SMs) relative to heterosexuals, and among SMs by gender. METHODS:
      Data were derived from the 2012-2013 National Epidemiologic Survey on Alcohol and
      Related Conditions-III. RESULTS: In the general noninstitutionalized population,
      1.5%, 1.3% and 0.5% of individuals self-identified as gay/lesbian, bisexual and
      not sure sexual orientations. Men were more likely to report gay/lesbian
      orientation than women (1.8% vs. 1.2%). Women were more likely than men to report
      bisexual (1.8% vs. 0.8%) and not sure (0.6% vs. 0.4%) sexual orientations.
      Sociodemographic characteristics varied across sexual orientation and gender.
      Relative to heterosexuals, disparities in substance use and psychiatric disorders
      were found across sexual orientations, especially among bisexual women. Greater
      rates of specific psychiatric disorders were also demonstrated by women reporting
      bisexual and not sure orientations relative to lesbian women, with fewer
      differences in rates of psychopathology among SM men. CONCLUSIONS: Despite
      growing acceptance of SMs and SM rights over the past decade, substantial mental
      health disparities exist among these subgroups of the U.S. noninstitutionalized
      population, especially among bisexual women. More research is needed to
      understand these mental health disparities, while considering nuances of multiple
      intersecting minority identities and unique contextual factors. FINDINGS:
      underscore the importance of advancing future population-based research that
      includes detailed information on the health and well-being of SMs in the United
      States.

PMID- 27883951
TI  - Survey of adaptive biasing potentials: comparisons and outlook.
AB  - Adaptive biasing potentials are becoming a standard tool of the trade for
      problems in chemistry, material science, biology, and drug discovery. These
      methods are easy to use, easy to distribute, reliable, and make otherwise
      impossible simulations possible. In this review we survey a number of adaptive
      bias potentials, and take a critical look at how they work. The biases fall into
      two basic classes, each having distinct attributes and levels of complexity. The
      vantage point from which the biases are discussed has only emerged in the last
      couple of years, and allows for a unified treatment of all the biases. We
      conclude with remarks about computational efficiency of the biases, which is
      largely overlooked in the current literature.

PMID- 27883949
TI  - Nicotine levels, withdrawal symptoms, and smoking reduction success in real world
      use: A comparison of cigarette smokers and dual users of both cigarettes and E
      cigarettes.
AB  - INTRODUCTION: To evaluate how experienced dual users used cigarettes and e
      cigarettes in real-world use and under different levels of cigarette
      availability. METHODS: Dual users (cigarettes+e-cigarettes; n=74) and a smoke
      only group (just cigarettes; n=74) engaged in a 26-day study with two ad lib use
      intervals, a week of 75% cigarette reduction and three days of 100% cigarette
      reduction. After a week of ad lib use of products, all participants were asked to
      reduce smoking by 75% (dual users were free to use their e-cigarettes as they
      wished), followed by another week of ad lib use. All participants were then asked
      to reduce smoking by 100% (cessation) for three days. Primary outcomes were
      biological samples (carbon monoxide, urinary nicotine and cotinine). Participants
      also provided real-time reports of product use, craving, and withdrawal symptoms
      using a smartphone app. RESULTS: Dual users did not smoke fewer cigarettes than
      smoke-only participants during ad lib periods, but quadrupled their use of e
      cigarettes during smoking reduction periods. Dual users were significantly more
      likely to maintain 100% reduction (97.1% vs. 81.2%). Amongst women, dual use was
      associated with higher nicotine levels and withdrawal suppression. DISCUSSION:
      Among a group of experienced dual users, e-cigarettes helped maintain smoking
      reduction and reduced some withdrawal symptoms, although both withdrawal symptoms
      and nicotine levels varied as a function of gender.

PMID- 27883950
TI  - The effects of social pressure and emotional expression on the cone of gaze in
      patients with social anxiety disorder.
AB  - BACKGROUND AND OBJECTIVES: Patients with social anxiety disorder suffer from
      pronounced fears in social situations. As gaze perception is crucial in these
      situations, we examined which factors influence the range of gaze directions
      where mutual gaze is experienced (the cone of gaze). METHODS: The social stimulus
      was modified by changing the number of people (heads) present and the emotional
      expression of their faces. Participants completed a psychophysical task, in which
      they had to adjust the eyes of a virtual head to gaze at the edge of the range
      where mutual eye-contact was experienced. RESULTS: The number of heads affected
      the width of the gaze cone: the more heads, the wider the gaze cone. The
      emotional expression of the virtual head had no consistent effect on the width of
      the gaze cone, it did however affect the emotional state of the participants.
      Angry expressions produced the highest arousal values. Highest valence emerged
      from happy faces, lowest valence from angry faces. CONCLUSION: These results
      suggest that the widening of the gaze cone in social anxiety disorder is not
      primarily mediated by their altered emotional reactivity. Implications for gaze
      assessment and gaze training in therapeutic contexts are discussed. LIMITATIONS:
      Due to interindividual variability, enlarged gaze cones are not necessarily
      indicative of social anxiety disorder, they merely constitute a correlate at the
      group level.

PMID- 27883952
TI  - Recent applications of metabolomics to advance microbial biofuel production.
AB  - Biofuel production from plant biomass is a promising source of renewable energy
      [1]. However, efficient biofuel production involves the complex task of
      engineering high-performance microorganisms, which requires detailed knowledge of
      metabolic function and regulation. This review highlights the potential of mass
      spectrometry-based metabolomic analysis to guide rational engineering of biofuel
      producing microbes. We discuss recent studies that apply knowledge gained from
      metabolomic analyses to increase the productivity of engineered pathways,
      characterize the metabolism of emerging biofuel producers, generate novel
      bioproducts, enable utilization of lignocellulosic feedstock, and improve the
      stress tolerance of biofuel producers.

PMID- 27883953
TI  - Thermogravimetric pyrolysis kinetics of bamboo waste via Asymmetric Double
      Sigmoidal (Asym2sig) function deconvolution.
AB  - Thermogravimetric kinetic of bamboo waste (BW) pyrolysis has been studied using
      Asymmetric Double Sigmoidal (Asym2sig) function deconvolution. Through
      deconvolution, BW pyrolytic profiles could be separated into three reactions
      well, each of which corresponded to pseudo hemicelluloses (P-HC), pseudo
      cellulose (P-CL), and pseudo lignin (P-LG) decomposition. Based on Friedman
      method, apparent activation energy of P-HC, P-CL, P-LG was found to be
      175.6kJ/mol, 199.7kJ/mol, and 158.4kJ/mol, respectively. Energy compensation
      effects (lnk0,z vs. Ez) of pseudo components were in well linearity, from which
      pre-exponential factors (k0) were determined as 6.22E+11s-1 (P-HC), 4.50E+14s-1
      (P-CL) and 1.3E+10s-1 (P-LG). Integral master-plots results showed pyrolytic
      mechanism of P-HC, P-CL, and P-LG was reaction order of f(alpha)=(1-alpha)2,
      f(alpha)=1-alpha and f(alpha)=(1-alpha)n(n=6-8), respectively. Mechanism of P-HC
      and P-CL could be further reconstructed to n-th order Avrami-Erofeyev model of
      f(alpha)=0.62(1-alpha)[-ln(1-alpha)]-0.61(n=0.62) and f(alpha)=1.08(1-alpha)[
      ln(1-alpha)]0.074 (n=1.08). Two-steps reaction was more suitable for P-LG
      pyrolysis.

PMID- 27883954
TI  - Feasibility of using a microalgal-bacterial consortium for treatment of toxic
      coke wastewater with concomitant production of microbial lipids.
AB  - This study examined the feasibility of using an algal-bacterial process for
      removal of phenol and NH4+-N from differently diluted coke wastewater with
      simultaneous production of biomass. Under illumination, microalgal-bacterial
      (MSB) cultures performed complete phenol degradation at all dilutions of coke
      wastewater while sole microalgal culture (MSA) degraded a maximum of 27.3% of
      phenol (initial concentration: 24.0mgL-1) from 5-fold diluted wastewater.
      Furthermore, the MSB culture had the highest rate of NH4+-N removal (8.3mgL-1d-1)
      and fatty acid production (20mgL-1d-1) which were 2.3- and 1.5-fold higher than
      those observed in the MSA cultures, probably due to decreases in toxic organic
      pollutants. Multivariate analyses indicated that co-cultivation of activated
      sludge was directly correlated with the elevated removals of phenol and NH4+-N.
      In the presence of sludge, adequate dilution of the coke wastewater can maximize
      the effect of bacteria on NH4+-N removal and biomass production.

PMID- 27883955
TI  - Prospects for energy recovery during hydrothermal and biological processing of
      waste biomass.
AB  - Thermochemical and biological processes represent promising technologies for
      converting wet biomasses, such as animal manure, organic waste, or algae, to
      energy. To convert biomass to energy and bio-chemicals in an economical manner,
      internal energy recovery should be maximized to reduce the use of external heat
      and power. In this study, two conversion pathways that couple hydrothermal
      liquefaction with anaerobic digestion or catalytic hydrothermal gasification were
      compared. Each of these platforms is followed by two alternative processes for
      gas utilization: 1) combined heat and power; and 2) combustion in a boiler. Pinch
      analysis was applied to integrate thermal streams among unit processes and
      improve the overall system efficiency. A techno-economic analysis was conducted
      to compare the feasibility of the four modeled scenarios under different market
      conditions. Our results show that a systems approach designed to recover internal
      heat and power can reduce external energy demands and increase the overall
      process sustainability.

PMID- 27883957
TI  - Effect of freezing prior to aging on myoglobin redox forms and CIE color of beef
      from Nellore and Aberdeen Angus cattle.
AB  - The objective of this study was to evaluate the effect of freezing prior to wet
      aging on the color of Nellore and Aberdeen Angus cattle meat. Samples of the
      Longissimus thoracis muscle were subjected to two treatments: conventional aging
      (0, 7, 14 and 21days); and freezing (-20 degrees C for 40days) followed by
      thawing and aging. Freezing promoted (P<0.05) formation of metmyoglobin during
      aging, especially in Nellore beef. Frozen meats showed (P<0.05) lower lightness
      (L*) values and higher redness (a*), chroma (C*) and hue angle (h*) values at the
      first day of storage, deteriorating quickly with aging time. The color of the
      Nellore meat was less (P<0.05) stable to freezing, being lighter, yellower and
      less red than Angus meat. The results suggest that color stability in vacuum
      packed beef is reduced by freezing prior to aging and that reduction depends on
      the animal breed.

PMID- 27883956
TI  - Efficacy of BRAF Inhibitors in Asian Metastatic Melanoma Patients: Potential
      Implications of Genomic Sequencing in BRAF-Mutated Melanoma.
AB  - BACKGROUND: The BRAF inhibitors vemurafenib and dabrafenib are currently the
      standard treatment for metastatic melanoma with BRAF V600 mutations. However,
      given the rarity of noncutaneous melanoma, including acral and mucosal subtypes,
      the efficacy of BRAF inhibitors for this subset of patients has not been
      extensively investigated. Acquired resistance generally appears 6 to 8 months
      after treatment with a BRAF inhibitor, and the mechanism of resistance is not
      well established. METHODS: We examined treatment outcomes for patients diagnosed
      with metastatic melanoma and treated with BRAF inhibitors at Samsung Medical
      Center between April 2013 and December 2015. We analyzed genomic alterations in
      selected patients using targeted sequencing. RESULTS: Twenty-seven patients with
      a median age of 49 years (range 23-82 years) with metastatic melanoma and treated
      with a BRAF inhibitor were identified. Of these patients, 19 (70.3%) had
      noncutaneous melanoma, including acral and mucosal melanoma. All patients had
      BRAFV600E mutations. The median progression-free survival of all patients was 9.2
      months (95% confidence interval, 1.6-16.7), and the objective response rate was
      78.9% in the mucosal/acral melanoma group and 75.0% in the cutaneous melanoma
      group. Three (11.1%) patients achieved complete response, and 19 (70.4%) showed a
      partial response. Targeted sequencing in five patients demonstrated NF1 mutations
      in three patients who did not respond to BRAF inhibitors. CONCLUSION: BRAF
      inhibitors were an effective therapeutic option for Korean patients with
      metastatic melanoma harboring a BRAF V600 mutation regardless of melanoma subtype
      (acral/mucosa versus cutaneous).

PMID- 27883958
TI  - Antimicrobial activity and bioguided fractionation of Rumex tingitanus extracts
      for meat preservation.
AB  - : This study was undertaken to investigate the antibacterial and antifungal
      activities of Rumex tingitanus leaves extracts as well as the identification of
      bioactive components and their performance in meat preservation. Total phenolics
      and flavonoids showed the highest content of phenolics and flavonoids in the
      ethyl acetate fraction (Rt EtOAcF). For antimicrobial efficacy, leaves extract
      and derived fraction were tested for their capacity to inhibit bacterial and
      fungal proliferation in vitro and in vivo. The ethyl acetate fraction showed the
      most potent antibacterial and antifungal activities compared to the others
      extracts. Thus, the efficacy of this extract to inhibit the proliferation of
      Listeria monocytogenes in minced beef meat model was examined. This fraction
      eradicates the L. monocytogenes population in meat in a concentration- and time
      dependent manner. A bio-guided purification of the Rt EtOAc fraction resulted in
      the isolation of the compound responsible for the observed antimicrobial
      activity. This compound was identified as luteolin by analysis of spectroscopic
      data. CHEMICAL COMPOUNDS ISOLATED IN THIS ARTICLE: Luteolin (PubChem CID:
      5280445); p-iodonitrotetrazolium chloride (PubChem CID: 64957); Amphotericin B
      (PubChem CID: 5280965); Gentamicin and (PubChem CID: 6419933); Hexane (PubChem
      CID: 8058); Methanol (PubChem CID: 887); Ethanol (PubChem CID: 702);
      Dimethylsulfoxide (PubChem CID: 679); Quercetin (PubChem CID: 5280343); Gallic
      acid (PubChem CID: 370).

PMID- 27883959
TI  - Evaluation of the effectiveness of non-irradiated and chlorine-free packaging for
      fresh beef preservation.
AB  - This study evaluates the potential of using non-irradiated barrier-shrink bags
      containing ethylene-vinyl alcohol copolymer (EVOH), polyamide (PA) and ethylene
      ionomer in their structures to preserve vacuum-packaged fresh beef as an
      alternative to traditional gamma-ray cross-linked bags containing polyvinylidene
      chloride (PVDC). Boneless beef rib eye roll cuts were vacuum-packed in an
      industrial processing plant using EVOH 44% mol, EVOH 32% mol and a control PVDC
      barrier shrink bags. The cuts were evaluated during storage at 0.5 degrees C. The
      EVOH films presented similar performance compared to control PVDC barrier shrink
      bags related to bacteria growth and purge loss. Packages with EVOH 32% mol film
      presented better performance than control bag with respect to the meat sensorial
      attributes, including fewer bubbles and better adhesion. EVOH 44% mol bags
      presented the highest rate of colour loss. The EVOH 32% mol non-irradiated and
      chlorine-free film is as effective for the preservation of fresh beef as
      traditional PVDC-irradiated shrink bags.

PMID- 27883960
TI  - A dual-potential electrochemiluminescence ratiometric sensor for sensitive
      detection of dopamine based on graphene-CdTe quantum dots and self-enhanced
      Ru(II) complex.
AB  - A novel dual-potential ratiometric electrochemiluminescence (ECL) sensor was
      designed for detecting dopamine (DA) based on graphene-CdTe quantum dots (G-CdTe
      QDs) as the cathodic emitter and self-enhanced Ru(II) composite (TAEA-Ru) as the
      anodic emitter. TAEA-Ru was prepared by linking ruthenium(II) tris(2,2'-bipyridyl
      4,4'-dicarboxylato) with tris(2-aminoethyl)amine. Firstly, 3
      aminopropyltriethoxysilane founctionalized G-CdTe QDs was used as the substrate
      for capturing target DA via the specific recognition of the diol of DA to the
      oxyethyl group of APTES. Then, Cu2O nanocrystals supported TAEA-Ru was further
      bound by the strong interaction between amino groups of DA and carboxyl groups of
      the Cu2O-TAEA-Ru. With the increase in DA concentration, the loading of Cu2O-TAEA
      Ru at the electrode increased. As a result, the anodic ECL signal from TAEA-Ru
      increased, and the cathodic ECL signal from G-CdTe QDs/O2 system decreased
      correspondingly. Such a decrease was resulted from the ECL resonance energy
      transfer (RET) from G-CdTe QDs to TAEA-Ru as well as the dual quenching effects
      of Cu2O to G-CdTe QDs, namely the ECL-RET from G-CdTe QDs to Cu2O and the
      consumption of coreactant O2 by Cu2O. Based on the ratio of two ECL signals, the
      determination of DA was achieved with a linear range from 10.0 fM to 1.0nM and a
      detection limit low to 2.9 fM (S/N=3). The combination of G-CdTe QDs/O2 and TAEA
      Ru would break the limitation of the same coreatant shared in previous ECL
      ratiometric systems and provide a potential application of ECL ratiometric sensor
      in the detection of biological small molecules with the assistance of the dual
      molecular recognition strategy.

PMID- 27883961
TI  - Molecular visualizing and quantifying immune-associated peroxynitrite fluxes in
      phagocytes and mouse inflammation model.
AB  - Reactions of peroxynitrite (ONOO-) with biomolecules can lead to cytotoxic and
      cytoprotective events. Due to the difficulty of directly and unambiguously
      measuring its levels, most of the beneficial effects associated with ONOO- in
      vivo remain controversial or poorly characterized. Recently, optical imaging has
      served as a powerful noninvasive approach to studying ONOO- in living systems.
      However, ratiometric probes for ONOO- are currently lacking. Herein, we report
      the design, synthesis, and biological evaluation of F482, a novel fluorescence
      indicator that relies on ONOO--induced diene oxidation. The remarkable
      sensitivity, selectivity, and photostability of F482 enabled us to visualize
      basal ONOO- in immune-stimulated phagocyte cells and quantify its generation in
      phagosomes by high-throughput flow cytometry analysis. With the aid of in vivo
      ONOO- imaging in a mouse inflammation model assisted by F482, we envision that
      F482 will find widespread applications in the study of the ONOO- biology
      associated with physiological and pathological processes in vitro and in vivo.

PMID- 27883962
TI  - Maternal care and affective behavior in female offspring: Implication of the
      neurosteroid/GABAergic system.
AB  - In female rats, the proestrus phase of the estrous cycle is associated with
      decreased levels of anxiety-like and depressive-like behavior relative to the
      metestrus phase. Progesterone likely modulate these behaviors, in part through
      the influence of its metabolite, allopregnanolone (THP) on hippocampal GABAAR
      subunit expression. As natural variations in maternal care have been found to
      influence both progesterone levels at proestrus and anxiety-like behavior in
      female offspring, we sought to investigate the importance of maternal care and
      the estrous cycle on affective behavior in female rats that had received Low or
      High levels of licking/grooming (LG) during early life. Subjects were tested for
      anxiety-like behavior in the elevated plus maze at proestrus or metestrus or for
      estrous cycle-dependent changes in depressive-like anhedonic behavior with a
      saccharin preference test. GABAAR subunit expression, and THP levels in the
      dorsal hippocampus and in plasma were also evaluated. Estrous cycle phase
      influenced saccharine preference and hippocampal THP level in both phenotypes.
      Low LG animals showed higher levels of hedonic behavior and anxiety-like
      behavior, irrespective of estrous cycle phase, as well as lower THP levels within
      the dorsal hippocampus when compared to High LG animals. Only High LG animals
      showed positive correlations between hippocampal THP levels and GABAAR subunit
      expression, suggesting a relative insensitivity to THP's modulation of these
      receptor subunits in Low LG offspring. These findings suggest that natural
      variations in maternal care influence anxiety-like and hedonic behavior through
      the modulation of the neurosteroid/GABAergic system.

PMID- 27883963
TI  - Hypothalamic-pituitary-adrenal axis activity and cognition in major depression:
      The role of remission status.
AB  - OBJECTIVES: Neuropsychological deficits and hypothalamic-pituitary-adrenal (HPA)
      axis dysfunction have been described in major depressive disorder (MDD). We
      conducted an exploratory study to investigate the role of remission status in the
      relationship between HPA axis and cognition in MDD. METHODS: Ninety-seven MDD
      patients (44 remitted, 53 non-remitted) and 97 healthy controls (HC) were
      evaluated. We measured verbal and visual memory, working memory, processing
      speed, attention, and executive function. Three HPA axis measures were assessed:
      cortisol awakening response (CAR), diurnal cortisol slope, and cortisol
      suppression ratio with 0.25mg of dexamethasone (DSTR). Multiple linear regression
      analyses were performed to study the relationship between cortisol measures and
      cognition while controlling for potential confounders. We conducted an overall
      analysis in all participants to compare both MDD-remitted and MDD non-remitted
      groups with respect to HC. Another analysis including MDD patients only was used
      to explore a moderating effect by remission status. RESULTS: MDD patients showed
      poorer cognitive performance compared with HC, without significant differences
      between remitters and non-remitters. Cortisol measures did not differ between
      remitters and non-remitters. Although most HPA axis measures were not associated
      with cognitive dysfunction, we found significant associations between cognitive
      performance in MDD-remitters and cortisol measures for visual memory, processing
      speed and executive function. A significant moderating effect for remission
      status was found between cortisol diurnal slope (but neither CAR nor DSTR) and
      performance in processing speed or executive function. CONCLUSIONS: Remission
      status in MDD appears to moderate the association between some cognitive domains
      (processing speed and executive function) and HPA axis activity.

PMID- 27883964
TI  - Sex-specific association between functional neuropeptide S receptor gene (NPSR1)
      variants and cortisol and central stress responses.
AB  - The brain neuropeptide S (NPS) system has recently generated substantial interest
      and may be of major relevance for central stress regulation. The NPS receptor
      (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced
      anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk
      between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been
      demonstrated. In humans, associations between NPSR1 variants and anxiety and
      panic disorder, as well as amygdala responsiveness to fear- relevant faces and
      prefrontal cortex activity in a fear conditioning paradigm have been reported.
      Moreover, a NPSR1 sequence variant was found to be associated with cortisol
      stress responses in males.Here, we performed a haplotype-based analysis covering
      three functional NPSR1 single nucleotide polymorphisms in the promoter
      (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects
      who were exposed to the Trier Social Stress Test (TSST). A significant sex
      specific association with salivary cortisol responses to acute psychosocial
      stress was detected for the common TTC haplotype 2 (frequency of about 20%). In
      an additional study using an imaging genetics approach, 65 healthy subjects were
      exposed to a stress paradigm for scanner environments ("ScanSTRESS"). We found a
      significant and, again, sex-specific interaction between rs324981 (whose minor T
      allele is harbored by haplotype 2) and the neural stress response in a cluster
      close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the
      TSST sample, NPSR1 variation was associated with salivary cortisol responses (on
      a trend level) in a sex-specific way.In summary, our preliminary findings in two
      independent cohorts exposed to different stress paradigms suggest that the NPS
      system significantly influences acute stress responses and that sequence
      variation in NPSR1 may contribute to sex differences in stress regulation.

PMID- 27883965
TI  - Frequency-independent characteristics of high-frequency oscillations in epileptic
      and non-epileptic regions.
AB  - OBJECTIVE: The purpose of the presented study is to determine whether there are
      frequency-independent high-frequency oscillation (HFO) parameters which may
      differ in epileptic and non-epileptic regions. METHODS: We studied 31 consecutive
      patients with medically intractable focal (temporal and extratemporal) epilepsies
      who were examined by either intracerebral or subdural electrodes. Automated
      detection was used to detect HFO. The characteristics (rate, amplitude, and
      duration) of HFO were statistically compared within three groups: the seizure
      onset zone (SOZ), the irritative zone (IZ), and areas outside the IZ and SOZ
      (nonSOZ/nonIZ). RESULTS: In all patients, fast ripples (FR) and ripples (R) were
      significantly more frequent and shorter in the SOZ than in the nonSOZ/nonIZ
      region. In the group of patients with favorable surgical outcomes, the relative
      amplitude of FR was higher in the SOZ than in the IZ and nonIZ/nonSOZ regions; in
      patients with poor outcomes, the results were reversed. The relative amplitude of
      R was significantly higher in the SOZ, with no difference between patients with
      poor and favorable surgical outcomes. CONCLUSIONS: FR are more frequent, shorter,
      and have higher relative amplitudes in the SOZ area than in other regions. The
      study suggests a worse prognosis in patients with higher amplitudes of FR outside
      the SOZ. SIGNIFICANCE: Various HFO parameters, especially of FR, differ in
      epileptic and non-epileptic regions. The amplitude and duration may be as
      important as the frequency band and rate of HFO in marking the seizure onset
      region or the epileptogenic area and may provide additional information on
      epileptogenicity.

PMID- 27883966
TI  - Influence of temperature, water activity and incubation time on fungal growth and
      production of ochratoxin A and zearalenone by toxigenic Aspergillus tubingensis
      and Fusarium incarnatum isolates in sorghum seeds.
AB  - The major objective of this study was to describe the effect of water activity
      and temperature on radial growth and production of ochratoxin A (OTA) and
      zearalenone (ZEA) on sorghum grains of three Aspergillus tubingensis and three
      Fusarium incarnatum isolates. The water activity range was 0.91-0.99 aw for F.
      incarnatum isolates and 0.88-0.99 aw for A. tubingensis isolates. Temperatures of
      incubation were 15, 25 and 37 degrees C for both species. Mycotoxin production
      was determined after 7, 14, 21 and 28days depending on the growth rate of the six
      isolates. Maximum growth rates (mm/day) were observed at 37 degrees C and 0.99 aw
      for A. tubingensis isolates and at 0.99 aw and 25 degrees C for F. incarnatum
      isolates. A. tubingensis was able to grow at 15 degrees C only at the highest aw
      levels (0.97 and 0.99 aw). However, at this temperature F. incarnatum grew at
      0.94 aw. Optimum ochratoxin A production was observed at 0.97 aw*37 degrees C
      whereas optimal conditions for ZEA production varied from one isolate to another.
      Moreover, isolates of F. incarnatum from Tunisia do not require high aw and
      temperature levels to yield maximum levels of ZEA. In general, our results showed
      that there is no correlation between the growth and production of ZEA in the case
      of F. incarnatum. This is the first study on the water activity and temperature
      effect on growth rate and ZEA production of F. incarnatum. Our results show that
      sorghum grains not only support growth but also OTA and ZEA production by A.
      tubingensis and F. incarnatum, respectively.

PMID- 27883967
TI  - Case report of migration of 2 ventriculoperitoneal shunt catheters to the
      scrotum: Use of an inguinal incision for retrieval, diagnostic laparoscopy and
      hernia repair.
AB  - BACKGROUD: Ventriculoperitoneal shunts are commonly used in the treatment of
      hydrocephalus, and catheter migration to various body sites has been reported.
      Pediatric and general surgeons are asked on occasion to assist with
      intraabdominal access for these shunts, particularly when there may be extensive
      adhesions or other complicating factors. METHODS: We describe a case in which an
      old shunt catheter was never removed from the abdomen, and it migrated through an
      inguinal hernia into the scrotum. The catheter became entangled and fibrosed to
      the testicle. A second and more recent shunt catheter was also in the scrotum. A
      single incision in the inguinal region was used to remove both shunt catheters,
      repair the inguinal hernia and perform diagnostic laparoscopy to assist in
      placing a new ventriculoperitoneal shunt. RESULTS: Prompt surgical removal is
      recommended for catheters remaining in the abdomen after ventriculoperitoneal
      shunt malfunction. These catheters may cause injury to the testicle, or possibly
      other intraabdominal organs. General or pediatric surgical consultation should be
      obtained for lost catheters or inguinal hernias. CONCLUSION: In the case of an
      inguinal hernia containing a fractured shunt catheter, the hernia sac can be used
      to remove the catheter, repair the hernia and gain laparoscopic access to the
      abdomen to assist with shunt placement.

PMID- 27883968
TI  - Vitamin D and outcomes in adult critically ill patients. A systematic review and
      meta-analysis of randomized trials.
AB  - PURPOSE: Low vitamin D blood levels are associated with high mortality in
      critically ill patients. There is controversy about vitamin D supplementation in
      this population. The objective of this meta-analysis was to evaluate if vitamin D
      administration reduces mortality in critically ill patients. MATERIALS AND
      METHODS: Online databases were searched up to September 1st, 2016 for randomized
      placebo-controlled trials on the use of vitamin D in adult patients with critical
      illness. The primary end point was mortality among trials with low risk of bias.
      The secondary end points were length of hospital stay, length of intensive care
      unit stay, length of mechanical ventilation, and adverse events. RESULTS: Seven
      studies published between 2011 and 2016, for a total of 716 patients, were
      included in the analysis. Vitamin D administration was associated with
      significantly lower mortality compared with placebo (101/320 [32%] in the vitamin
      D group vs 123/307 [40%] in the placebo group; odds ratio, 0.70 [95% confidence
      interval, 0.50 to 0.98]; P=.04; I2=0%). No differences in adverse events and
      other secondary end points were found. CONCLUSIONS: In critically ill patients,
      vitamin D administration might be associated with a reduction in mortality
      without significant adverse events. A large multicenter randomized trial should
      conclusively confirm these findings.

PMID- 27883969
TI  - Drug-drug interactions in the intensive care unit: Do they really matter?
AB  - PURPOSE: To describe prevalence and patterns of potential drug-drug interactions
      (pDDIs) in the intensive care unit (ICU), occurrence of adverse drug events
      (ADEs), and agreement between different compendia and intensivists' perceptions.
      METHODS: A cross-sectional study. Drug profiles of all adult patients from 2
      academic ICUs were screened on day 3 upon admission. We identified pDDIs using 3
      compendia (Stockley's, Micromedex, and Epocrates) and documented their mechanism
      of action, clinical consequences, severity, level of evidence, and management.
      Medical records were searched to identify ADEs potentially related to major
      pDDIs. Agreement between information sources (compendia, intensivists) was
      evaluated. RESULTS: We identified 1120 pDDIs among 275 patients. Median number of
      pDDIs per patient was 3.0 (interquartile range, 1-6), with 79% of patients
      presenting with at least 1 pDDI. Major pDDIs were detected in 18% of patients,
      with potentially related to ADEs in 4% of patients. Only 13% of all pDDIs were
      documented simultaneously in all 3 compendia. Different information sources
      (compendia, clinicians) showed "no" to "fair" agreement. CONCLUSIONS: Potential
      drug-drug interactions occurred in most ICU patients, contrasting with low rates
      of potentially related ADEs, which may have been underestimated. Sources of
      information are inconsistent, challenging the identification of pDDIs.

PMID- 27883970
TI  - Association between dengue fever incidence and meteorological factors in
      Guangzhou, China, 2005-2014.
AB  - This study aims to (1) investigate the associations between climatic factors and
      dengue; and (2) identify the susceptible subgroups. De-identified daily dengue
      cases in Guangzhou for 2005-2014 were obtained from the Chinese Center for
      Disease Control and Prevention. Weather data were downloaded from the China
      Meteorological Data Sharing Service System. Distributed lag non-linear models
      (DLNM) were used to graphically demonstrate the three-dimensional temperature
      dengue association. Generalised estimating equation models (GEE) with piecewise
      linear spline functions were used to quantify the temperature-dengue
      associations. Threshold values were estimated using a broken-stick model. Middle
      aged and older people, people undertaking household duties, retirees, and those
      unemployed were at high risk of dengue. Reversed U-shaped non-linear associations
      were found between ambient temperature, relative humidity, extreme wind velocity,
      and dengue. The optimal maximum temperature (Tmax) range for dengue transmission
      in Guangzhou was 21.6-32.9 degrees C, and 11.2-23.7 degrees C for minimum
      temperature (Tmin). A 1 degrees C increase of Tmax and Tmin within these ranges
      was associated with 11.9% and 9.9% increase in dengue at lag0, respectively.
      Although lag effects of temperature were observed for up to 141 days for Tmax and
      150 days for Tmin, the maximum lag effects were observed at 32 days and 39 days
      respectively. Average relative humidity was negatively associated with dengue
      when it exceeded 78.9%. Maximum wind velocity (>10.7m/s) inhibited dengue
      transmission. Climatic factors had significant impacts on dengue in Guangzhou.
      Lag effects of temperature on dengue lasted the local whole epidemic season. To
      reduce the likely increasing dengue burden, more efforts are needed to strengthen
      the capacity building of public health systems.

PMID- 27883971
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin and the viral infection.
AB  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widespread highly toxic
      environmental contaminant, suppresses immune response and leads to an increased
      susceptibility to infectious agents. In particular, several studies have provided
      evidence that TCDD decreases resistance to numerous viruses. Indeed, in vivo and
      in vitro investigations showed that the presence of TCDD is able to interfere
      with the replication of both human and animal viruses, such as influenza A
      viruses, coxsackie virus B3, immunodeficiency virus type-1 (HIV-1),
      cytomegalovirus (CMV), herpes simplex II, and bovine herpesvirus 1. Moreover,
      TCDD could induce an exacerbation of latent infection produced by HIV-1, CMV or
      Epstein-Barr virus. In this review, we first describe the general effects of TCDD
      exposure on mammalian cells, then we focus on its influence on the viral
      infections. Overall, the available data support the concept that TCDD exposure
      may act as an additional risk factor in promoting of viral diseases.

PMID- 27883973
TI  - Left ventricular adaptation after TAVI evaluated by conventional and speckle
      tracking echocardiography.
AB  - OBJECTIVE: Our study aimed to evaluate myocardial adaption and outcome after
      transfemoral aortic valve implantation (TAVI TF) for severe aortic stenosis by LV
      ejection fraction (LVEF) and speckle tracking analysis. METHODS AND RESULTS: From
      168 patients who underwent TAVI TF between 2010 and 2013 in our institution, n=95
      with a follow-up period >=3months were included and grouped (G) according to
      baseline left ventricular ejection fraction (LVEF; G1: LVEF<40%, G2: 40%-55%, G3:
      >55%). LV function was evaluated using conventional and speckle-tracking based
      parameters. Mortality was tracked up to 60months. Aortic valve orifice diameter
      and mean aortic gradient improved significantly after TAVI. LV dimensions and
      LVEF remained largely unchanged. Systolic function significantly improved in G1
      (LVEF, p<0.001, global longitudinal strain [GLS], p=0.02) but deteriorated in G3
      (LVEF, p=0.004, GLS, p=0.03). It did not change in G2. Diastolic function
      parameters improved significantly only in G3. Changes of LVEF and GLS were also
      statistically significant between G1 and G3 (LVEF p<0.0001, GLS p=0.004).
      Patients exhibited a higher survival rate with an LVEF increase >8% than with
      LVEF deterioration >8% (p=0.04). GLS changes had no significant impact on
      mortality. CONCLUSION: In patient with aortic stenosis and LVEF impairment at
      baseline, TAVI results in an improved LVEF, while patients with a high LVEF at
      baseline experience a normalization of LVEF after TAVI. Independent of the
      baseline value, a deterioration of LVEF leads to a significant increase in
      mortality.

PMID- 27883974
TI  - Is undersized self-expandable prosthesis a valuable selection for transcatheter
      aortic valve replacement in high risk bicuspid aortic valve stenosis? Report of
      two successful cases.

PMID- 27883972
TI  - Rheumatic heart disease in a developing country: Incidence and trend (Monastir;
      Tunisia: 2000-2013).
AB  - BACKGROUND: The penicillin therapy of beta hemolytic streptococcal pharyngitis
      has aided in the decrease of rheumatic heart disease (RHD) in developing
      countries. Tunisia is an endemic area, however, and incidence of RHD is weakly
      documented. We aimed at establishing the standardized incidence rate (SIR) of RHD
      in Monastir governorate and at determining RHD prevalence among hospitalized
      patients in two cardiology departments. METHODS: From the regional register of
      Monastir Hospital morbidity, we have selected newly diagnosed patients with RHD,
      residents of Monastir, and hospitalized to the 2 cardiology departments between
      2000 and 2013 (2001 not included). FINDINGS: We studied 676 newly admitted
      patients. We estimate 1060 to be the number of new annual RHD cases in Tunisia.
      The SIR per 105 person-years was 10.97, being 9.3 in men and 19.1 in women,
      respectively. We have notified a negative trend of crude incidence rate/105
      Inhabitants (Inh) (CIR) (r=-0.23, p<10-3), and a strong positive correlation
      between age and CIR/105 Inh (r=0.989, p<10-4). RHD lethality was 1%. We have
      registered 728 hospitalizations for RHD, representing 2.5% of all cardiology
      hospitalizations [95% CI: 2.3-2.7%], with a prevalence for 13.3% for women aged
      15-29years. The median hospital stay was 9days (IQR: 5-15). CONCLUSION: Our
      results confirm the RHD incidence decrease, consistent with epidemiological
      transition in Tunisia. We have also emphasized on the close trend of RHD with age
      and the predominance of RHD among women especially at the procreation age.

PMID- 27883975
TI  - Evaluation of current practices in transcatheter aortic valve implantation: The
      WRITTEN (WoRldwIde TAVI ExperieNce) survey.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been adopted
      worldwide as the standard treatment for severe aortic stenosis in symptomatic
      patients at prohibitive or high surgical risk, but there are still several areas
      where consensus and evidence are lacking. The purpose was to obtain a global view
      of current practice related to TAVI with the potential to identify the main areas
      of consensus and divergence between centers. METHODS: An online questionnaire was
      distributed in centers performing TAVI including a total of 59 questions
      concerning pre-procedural evaluation, procedural practices and post-procedural
      management. RESULTS: The survey was completed by 250 centers (with a cumulative
      experience of nearly 70,000 TAVI) from 38 different countries. Heart team
      meetings and surgical risk scores were routinely performed in most (>95%)
      centers, but frailty (44%) and quality of life (28%) assessments were less
      frequently performed. General anesthesia remained the most frequent type of
      anesthesia (60% of centers), and significant variability was detected in the
      examinations for residual aortic regurgitation assessment during the procedure
      and in post-procedural ECG monitoring and temporary pacemaker implementation
      (from none to >=72h post-TAVI). Dual antiplatelet therapy duration post-TAVI was
      highly variable (1, 3, and >=6months in 14%, 41% and 32% of centers,
      respectively) and lack of consensus in antithrombotic regimen was observed in
      patients with atrial fibrillation requiring anticoagulation therapy
      (anticoagulation alone, anticoagulation+aspirin, anticoagulation+clopidogrel, and
      triple therapy in 28%, 37%, 26% and 4% of centers, respectively). CONCLUSIONS:
      The WRITTEN survey provided extensive data on current TAVI-related practice and
      identified important differences between centers in key aspects of pre-, intra-,
      and post-operative management. This highlights the urgent need for further
      studies and evidence-based data to guide multiple aspects of the TAVI field.

PMID- 27883976
TI  - Prognostic value of liver dysfunction assessed by MELD-XI scoring system in
      patients undergoing transcatheter aortic valve implantation.
AB  - BACKGROUND: There are limited data regarding the influence of liver dysfunction
      on outcomes of transcatheter aortic valve implantation (TAVI). Model for End
      stage Liver Disease eXcluding International normalized ratio (MELD-XI) score,
      which was originally developed for patients with cirrhosis awaiting liver
      transplantation, has been reported as a predictor of heart disease. The aim of
      this study was to investigate the prognostic value of MELD-XI score for patients
      undergoing TAVI. METHODS: Data from the prospectively maintained Optimized
      transCathEter vAlvular iNtervention (OCEAN-TAVI) multicenter registry were
      collected in 749 patients who underwent TAVI between October 2013 and August
      2015. MELD-XI score was calculated as follows: 11.76*Ln (creatinine)+5.11*Ln
      (total bilirubin)+9.44. Patients were categorized based on MELD-XI score>10 or
      <=10, and compared with regard to clinical characteristics and outcomes of TAVI.
      RESULTS: Higher MELD-XI score was associated with lower 30-day survival (95.6% vs
      98.5%, P=0.03). Kaplan-Meier analysis revealed that higher MELD-XI score also was
      associated with lower 6-month survival (P<0.01). Multivariate Cox regression
      analysis showed that MELD-XI score was an independent predictor of 6-month
      cumulative mortality. Receiver operating characteristic analysis revealed that
      MELD-XI score showed better accuracy in predicting 6-month mortality compared
      with Logistic European System for Cardiac Operative Risk Evaluation, European
      System for Cardiac Operative Risk Evaluation II, and Society of Thoracic Surgeons
      scores (area under the curve=0.67, 0.58, 0.57, and 0.60, respectively).
      CONCLUSION: Evaluation of liver dysfunction according to MELD-XI score provides
      additional risk information for patients undergoing TAVI.

PMID- 27883977
TI  - Age-related changes of thoracic aorta geometry used to predict the risk for acute
      type B dissection.
AB  - AIMS: Risk models that use a single aortic diameter threshold have failed to
      successfully predict acute type B aortic dissection (TBAD). We sought to identify
      meaningful age-indexed anatomical variables to predict TBAD risk. METHODS AND
      RESULTS: A geometric deformable model, consisting of virtual elastic balloons
      that inflate inside a vessel lumen, was developed to quantify thoracic aorta
      geometry. In the presence of TBAD, true and total artery lumen morphology were
      assessed. A stepwise logistic model was built to predict TBAD risk. Initial
      covariates included age, gender, body mass index and all anatomic variables not
      directly related to the dissected segment. Patients with acute TBAD (n=34, 62+/
      12years old, 57% male gender) were compared with subjects with symptoms of
      dissection, but with a subsequent negative diagnosis (n=51, 62+/-12years old, 76%
      male gender). Patient risk factors did not differ between groups. Most aortic
      anatomical variables were age-dependent. Aortic size was larger in every segment
      of the dissected with respect to non-dissected aortas (p<0.001). Variables
      entering the TBAD risk prediction model were aortic arch diameter, thoracic aorta
      length and age (predictability=0.9764, r=0.85), confirmed by a bootstrap internal
      validation. In dissected aortas, the true lumen volume was correlated to age
      (r=0.72). CONCLUSIONS: TBAD probability increases with a larger aortic arch
      diameter and a longer thoracic aorta, whereas threshold values increase with age.
      The aortic morphology was age-dependent. After dissection, true lumen volume
      correlated to age. The use of threshold values indexed to age should be
      encouraged to better prevent and eventually treat TBAD.

PMID- 27883978
TI  - Outcomes of borderline rheumatic heart disease: A prospective cohort study.
AB  - CONTEXT AND AIMS: The advent of systematic screening for rheumatic heart disease
      (RHD) by echocardiography in endemic regions has led to a new entity: borderline
      RHD. The pathogenicity and natural history of borderline RHD needs to be
      addressed. The aim of this study was to assess the outcomes of children detected
      by echocardiography as having borderline RHD. METHODS: Schoolchildren in 4th
      grade (i.e., aged 9-10years) who were prospectively echo-screened for RHD (2012
      2014) in Noumea, New Caledonia, were asked to participate. Children with
      borderline RHD according to consistent independent review by two cardiologists
      were included and followed-up in 2015. RESULTS: Among the 8684 schoolchildren
      screened, 49 were diagnosed with borderline RHD according to the Cardiologist
      clinically involved in the child's management plan. After independent review by
      two cardiologists, 25 children were consistently diagnosed with borderline RHD
      and included in the follow-up study. Overall, inter-observer agreement was
      moderate with diagnostic kappa values of 0.63 (95% CI 0.45-0.78). After a median
      follow-up of 23months (IQR (20.5-33.0), 15 children (60.0%) had stability of
      valvular lesions, 8 (32.0%) had normal findings according to the WHF criteria.
      Two children (8.0%) had definite RHD on the follow-up echocardiogram, but no
      clinical events or audible pathological murmur during the study period. No factor
      could be identified as prognostic of either stability or progression.
      CONCLUSIONS: Borderline RHD diagnosed by systematic screening in high-risk
      populations remains mostly unchanged at 2years follow-up. Diagnosis of borderline
      RHD may require two reviewers for consistency.

PMID- 27883979
TI  - Low NT-proBNP levels: An early sign for the diagnosis of ischemic heart failure.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is seen to be
      mostly elevated in patients with acute heart failure (AHF). However, cases of AHF
      presenting with low NT-proBNP levels have been reported. In this study designed
      to investigate the factors associated with low NT-proBNP levels in AHF patients,
      we discovered that etiology and related factors have an influence on NT-proBNP
      levels. METHODS: In this study, 154 AHF patients met the study criteria (117 men,
      median age 74years; left ventricular ejection fraction [LVEF] 46+/-13%; New York
      Heart Association [NYHA] classes II-IV). We analyzed the different clinical
      variables of patients based on plasma NT-proBNP levels. In addition, we
      identified the differences in NT-proBNP levels between ischemic and non-ischemic
      etiologies, as well as the relationships between time from symptom onset to ED
      visit and NT-proBNP levels. RESULTS: The group with low NT-proBNP levels showed
      an ischemic association, higher LVEF, lower NYHA class and shorter time from
      symptom onset to ED visit. Plasma NT-proBNP levels were lower in the ischemic
      group than in the non-ischemic group (P<0.01). Meanwhile, NT-proBNP levels were
      relatively low in patients during early phases of AHF hospitalization and
      increased with time from symptom onset to ED visit (P<0.01). CONCLUSION: We
      inferred that low NT-proBNP levels may infer the ischemic etiology especially in
      patients with normal LVEF in the early phases of AHF hospitalization.

PMID- 27883980
TI  - Progression of coronary artery calcium in Japanese American men and white men in
      the ERA JUMP study.
AB  - BACKGROUND: Progression of coronary artery calcium (CAC) is associated with
      increased risk of coronary heart disease (CHD) and is reported to be greater in
      whites than blacks, Hispanics, and Chinese in the US. Our objective was to
      compare progression of CAC between Japanese Americans and whites. METHODS:
      Population-based sample of 303 Japanese American men and 310 white men aged 40
      49years, free of clinical cardiovascular disease at baseline, were examined for
      CAC at baseline (2004-2007) and follow-up (2008-2013). Progression of CAC was
      defined as change in coronary calcium scores (CCS) in participants with baseline
      CCS>0 and incident CAC in participants with baseline CCS=0. Multiple linear
      regression and relative risk regression were used to compare change in CCS scores
      and incident CAC between the two races, respectively. RESULTS: Japanese American
      men had significantly greater annual change in CCS than white men (median
      [interquartile range]: 11.3 Agatston units [1.4, 24.9] vs 2.5 [-0.22, 14.5]) in
      the unadjusted analyses. After adjusting for cardiovascular risk factors and
      follow-up time, change in CCS (beta+/-CI) and incidence rate ratio of CAC was
      similar in Japanese American men and white men: -0.12 (-0.34, 0.15) and (0.87
      [95% CI: 0.20, 3.9]), respectively. CONCLUSIONS: In contrast to previously
      reported greater progression of CAC in whites than other races, we found a
      similar progression of CAC in Japanese American men as white men. Our study
      identifies Japanese American men as a target group for prevention of CHD. Large
      prospective studies are warranted to confirm these findings.

PMID- 27883981
TI  - Staging of third molar development in relation to chronological age of 5-16 year
      old Indian children.
AB  - BACKGROUND: The usefulness of the developmental status of the third molar has
      been studied in assessment of the chronological age of adolescents in whom the
      development of the other permanent teeth is nearly complete. However, little is
      known about the timing and pattern of third-molar development in the Indian
      population. AIM: This study aimed to stage the third molar development in
      relation to chronological age of 5-16year old Indian children. DESIGN: In this
      cross-sectional observational study, the status of third molar development in
      relation to chronological age of 1139 Indian children aged 5-16 years was
      evaluated radiographically, using Orhan's modification of Demirjian's method.
      RESULTS: The frequency of occurrence of the third molars varied from 47% to 70%.
      Crypt formation, crown completion and root completion occurred as early as 5.4,
      8.7 and 15.0 years, respectively. No significant differences based on gender or
      side were observed in third-molar development (p>0.05). For most stages,
      maxillary third molars were slightly more advanced than their mandibular
      counterparts (p>0.05). CONCLUSION: Considering the high degree of variability
      observed in third molar genesis and development, the usefulness of this tooth in
      age determination studies may be very limited in the age group studied.

PMID- 27883982
TI  - Exocranial surfaces for sex assessment of the human cranium.
AB  - Determination of sex is one of the most important and challenging disciplines in
      biological anthropology. Creating a robust tool for sexing crania is crucial for
      forensic anthropology, especially in this period of migration, travel, and
      globalization, when different populations are mixed together in one region. Many
      different approaches to sex estimation using the skull have been published;
      however, population specificity and oscillation of variable sexual dimorphism
      typically reduces their effectiveness. The aim of this study was to create a
      robust classifier using virtual anthropology without the use of a CT scanner. The
      entire cranial surface was analyzed using coherent point drift-dense
      correspondence analysis and classification was performed using a support vector
      machine with a radial kernel, minimizing subjective error. The study sample
      consisted of 103 CT scans of a recent southern French population. Virtual scans
      of 52 males and 51 females (age from 18 to 92) were analyzed using 3D software
      systems (Rapidform, Avizo, Morphome3cs) and innovative approaches in geometric
      morphometrics. Leave-one-out crossvalidation was also applied. Sex differences in
      shape and form were displayed by colour scale maps. The whole cranial surface was
      significantly different between males and females in size (form). Sexual
      dimorphism was significantly lower in senile skulls. The most exclusive areas
      were the supraorbital region, orbits, cheek bones, nasal apertures, mastoids, and
      external occipital protuberances. The method provided a high level of
      classification accuracy (90.3%) in sexing male and female skulls and is a
      valuable tool for sex determination.

PMID- 27883983
TI  - Loss and replacement of small particles on the contact surfaces of footwear
      during successive exposures.
AB  - On the contact surfaces of footwear loosely, moderately and strongly held
      particle fractions were separated and analyzed in an effort to detect different
      particle signals. Three environmental exposure sites were chosen to have
      different, characteristic particle types (soil minerals). Shoes of two types
      (work boots and tennis shoes) were tested, accumulating particles by walking 250m
      in each environment. Some shoes were exposed to only one environment; others were
      exposed to all three, in one of six different sequences. Sampling methods were
      developed to separate particles from the contact surface of the shoe based on how
      tightly they were held to the sole. Loosely held particles were removed by
      walking on paper, moderately held particles were removed by electrostatic
      lifting, and the most tightly held particles were removed by moist swabbing. The
      resulting numbers and types of particles were determined using forensic
      microscopy. Particle profiles from the different fractions were compared to test
      the ability to objectively distinguish the order of exposure to the three
      environments. Without exception, the samples resulting from differential sampling
      are dominated by the third site in the sequential footwear exposures. No
      noticeable differences are seen among the differential samplings of the loosely,
      moderately and strongly held particles: the same overwhelming presence of the
      third site is seen. It is clear from these results (1) that the third (final)
      exposure results in the nearly complete removal of any particles from prior
      exposures, and (2) that under the experimental conditions loosely, moderately and
      strongly held particles are affected similarly, without any detectable enrichment
      of the earlier exposures among the more tightly held particles. These findings
      have significant implications for casework, demonstrating that particles on the
      contact surfaces of footwear are rapidly lost and replaced.

PMID- 27883984
TI  - Car speed estimation based on cross-ratio using video data of car-mounted camera
      (black box).
AB  - This paper proposes several methods for using footages of car-mounted camera (car
      black box) to estimate the speed of the car with the camera, or the speed of
      other cars. This enables estimating car velocities directly from recorded
      footages without the need of specific physical locations of cars shown in the
      recorded material. To achieve this, this study collected 96 cases of black box
      footages and classified them for analysis based on various factors such as travel
      circumstances and directions. With these data, several case studies relating to
      speed estimation of camera-mounted car and other cars in recorded footage while
      the camera-mounted car is stationary, or moving, have been conducted.
      Additionally, a rough method for estimating the speed of other cars moving
      through a curvilinear path and its analysis results are described, for practical
      uses. Speed estimations made using cross-ratio were compared with the results of
      the traditional footage-analysis method and GPS calculation results for camera
      mounted cars, proving its applicability.

PMID- 27883985
TI  - A systematic review of passive exposure to cannabis.
AB  - Passive exposure to cannabis smoke may induce effects on behavior and psychomotor
      skills, and have legal consequences, including the risk of being falsely
      considered as a cannabis user. This can become a concern, especially in
      occupational contexts or when driving vehicles. In order to enable a
      differentiation between a passive and an active exposure to cannabis and to limit
      the likeliness to be detected positive following passive exposure, this review
      identified specific biomarkers of passive exposure in urine, blood, oral fluid,
      hair, and sebum. Out of 958 papers identified on passive exposure to cannabis, 21
      were selected. Although positive tests had been observed in all matrices
      following extremely high passive exposure, some distinctive features were
      observed in each matrix compared to cannabis active use. More specifically, in
      everyday life conditions, 11-nor-delta-9-THC-carboxylic acid (THC-COOH) urinary
      level should be detected below the positivity threshold used to confirm active
      smoking of cannabis, especially after normalization to creatinine level.
      Measuring delta-9-tetrahydrocannabinol (THC) and THC-COOH in blood is an
      appropriate alternative for appraising passive exposure as low and very low
      concentrations of THC and THC-COOH, respectively, should be measured. In hair,
      oral fluid (OF) and sweat/sebum emulsion, no THCCOOH should be detected. Its
      presence in hair argues for regular cannabis consumption and in OF or sweat for
      recent consumption. The experts should recommend to persons who have to
      demonstrate abstinence from cannabis to avoid heavily smoky and unventilated
      environments.

PMID- 27883986
TI  - A model of free-living gait: A factor analysis in Parkinson's disease.
AB  - INTRODUCTION: Gait is a marker of global health, cognition and falls risk. Gait
      is complex, comprised of multiple characteristics sensitive to survival, age and
      pathology. Due to covariance amongst characteristics, conceptual gait models have
      been established to reduce redundancy and aid interpretation. Previous models
      have been derived from laboratory gait assessments which are costly in equipment
      and time. Body-worn monitors (BWM) allow for free-living, low-cost and continuous
      gait measurement and produce similar covariant gait characteristics. A BWM gait
      model from both controlled and free-living measurement has not yet been
      established, limiting utility. METHODS: 103 control and 67 PD participants
      completed a controlled laboratory assessment; walking for two minutes around a
      circuit wearing a BWM. 89 control and 58 PD participants were assessed in free
      living, completing normal activities for 7 days wearing a BWM. Fourteen gait
      characteristics were derived from the BWM, selected according to a previous
      model. Principle component analysis derived factor loadings of gait
      characteristics. RESULTS: Four gait domains were derived for both groups and
      conditions; pace, rhythm, variability and asymmetry. Domains totalled 84.84% and
      88.43% of variance for controlled and 90.00% and 93.03% of variance in free
      living environments for control and PD participants respectively. Gait
      characteristic loading was unambiguous for all characteristics apart from gait
      variability which demonstrated cross-loading for both groups and environments.
      The model was highly congruent with the original model. CONCLUSIONS: The
      conceptual gait models remained stable using a BWM in controlled and free-living
      environments. The model became more discrete supporting utility of the gait model
      for free-living gait.

PMID- 27883987
TI  - Changes in lumbopelvic rhythm during trunk extension in adolescent soccer
      players.
AB  - Many adolescent athletes experience low back pain (LBP). Its causative factors
      include lower limb muscle tightness and hip-spine incoordination. Hip-spine
      coordination [or lumbopelvic rhythm, LPR] can be used to assess lower-limb and
      spine functions. We assessed the presence/absence of LBP in adolescent soccer
      players before and after a six-month period and divided them into four groups: no
      LBP both before and after the period (NBP group); LBP before but not after (PN
      group); LBP after but not before (NP group); and LBP both before and after (LBP
      group). We used a 3D motion analysis system during trunk extension to measure the
      lumbar spine and hip ranges of motion (ROMs). On comparing the results obtained
      before and after the six-month period, lumbar spine ROM decreased in the NP
      group, hip ROM increased in the LBP group. From before to after the period, the
      linear prediction indicated that, when the hip extends by 1 degrees , the lumbar
      spine extends by 3.5 degrees -3.2 degrees  for the PN group and by 3.4 degrees 
      2.8 degrees  for the NP group. The NP group extended their lumbar spine
      excessively compared with the hip before the period, which could cause LBP, but
      decreased the extension after the period. Lumbar extension relative to hip
      extension decreased in the PN group, which could decrease excessive load on the
      lumbar spine and eliminate LBP. These findings suggest that to prevent LBP in
      adolescent soccer players, it is important to restrict lumbar spine extension
      relative to hip extension.

PMID- 27883988
TI  - Real-time feedback to improve gait in children with cerebral palsy.
AB  - Real-time feedback may be useful for enhancing information gained from clinical
      gait analysis of children with cerebral palsy (CP). It may also be effective in
      functional gait training, however, it is not known if children with CP can adapt
      gait in response to real-time feedback of kinematic parameters. Sixteen children
      with cerebral palsy (age 6-16; GMFCS I-III), walking with a flexed-knee gait
      pattern, walked on an instrumented treadmill with virtual reality in three
      conditions: regular walking without feedback (NF), feedback on hip angle (FH) and
      feedback on knee angle (FK). Clinically relevant gait parameters were calculated
      and the gait profile score (GPS) was used as a measure of overall gait changes
      between conditions. All children, except one, were able to improve hip and/or
      knee extension during gait in response to feedback, with nine achieving a
      clinically relevant improvement. Peak hip extension improved significantly by
      5.1+/-5.9 degrees  (NF: 8.9+/-12.8 degrees , FH: 3.8+/-10.4 degrees , p=0.01).
      Peak knee extension improved significantly by 7.7+/-7.1 degrees  (NF: 22.2+/-12.0
      degrees , FK: 14.5+/-12.7 degrees , p<0.01). GPS did not change between
      conditions due to increased deviations in other gait parameters. Responders to
      feedback were shown to have worse initial gait as measured by GPS (p=0.005) and
      functional selectivity score (p=0.049). In conclusion, ambulatory children with
      CP show adaptability in gait and are able to respond to real-time feedback,
      resulting in significant and clinically relevant improvements in peak hip and
      knee extension. These findings show the potential of real-time feedback as a tool
      for functional gait training and advanced gait analysis in CP.

PMID- 27883990
TI  - Force-distance curves on lubricant films: An approach to the characterization of
      the shape of the AFM tip.
AB  - Force-distance curves have been acquired with an atomic force microscope on
      perfluorpolyether films. It is shown that curves acquired on films of different
      thickness, at different rates and with different dwell times can be overlapped by
      rescaling the time or distance axis. When the time or distance axis is rescaled,
      the force depends only on the surface tension of perfluorpolyether and on
      geometrical properties of the tip (aperture and perimeter of the tip at a given
      distance from the apex). Hence, curves acquired with the same tip overlap. By
      comparing curves acquired at different rates the dynamics of tip-wetting can be
      investigated. Furthermore, rescaled force-distance curves have been matched with
      the perimeter of cross sections of the tip, i.e. with the perimeter of the three
      phase contact line. Such measurements pave the way for a non-destructive
      investigation of the tip shape.

PMID- 27883989
TI  - Recombinant anthrax protective antigen: Observation of aggregation phenomena by
      TEM reveals specific effects of sterols.
AB  - Negatively stained transmission electron microscope images are presented that
      depict the aggregation of recombinant anthrax protective antigen (rPA83 monomer
      and the PA63 prepore oligomer) under varying in vitro biochemical conditions.
      Heat treatment (50 degrees C) of rPA83 produced clumped fibrils, but following
      heating the PA63 prepore formed disordered aggregates. Freeze-thaw treatment of
      the PA63 prepore generated linear flexuous aggregates of the heptameric
      oligomers. Aqueous suspensions of cholesterol microcrystals were shown to bind
      small rPA83 aggregates at the edges of the planar bilayers. With PA63 a more
      discrete binding of the prepores to the crystalline cholesterol bilayer edges
      occurs. Sodium deoxycholate (NaDOC) treatment of rPA83 produced quasi helical
      fibrillar aggregate, similar but not identical to that produced by heat
      treatment. Remarkably, NaDOC treatment of the PA63 prepores induced
      transformation into pores, with a characteristic extended beta-barrel. The PA63
      pores aggregated as dimers, that aggregated further as angular chains and closed
      structures in higher NaDOC concentrations. The significance of the sterol
      interaction is discussed in relation to its likely importance for PA action in
      vivo.

PMID- 27883991
TI  - A comparative morphological study of the epiandrous apparatus in mygalomorph
      spiders (Araneae, Mygalomorphae).
AB  - Many adult male spiders have silk glands which are not associated with the
      spinnerets. They occur on the anterior margin of the genital furrow and are used
      during the building of the sperm web and sperm droplet induction. These
      epiandrous glands exit the body through ducts which lead to specialized spigots.
      In the taxon Mygalomorphae, the presence of epiandrous spigots is just reported
      for a couple of species but their morphology has not been investigated. In this
      paper we provide a detailed study of the ultrastructure morphology of eighteen
      species belonging to eight families using light and scanning electron microscopy
      (SEM). We describe and present images of the epiandrous spigots above the genital
      opening. Also, we compare the morphology of spigots between families and describe
      the epiandrous glands through histology.

PMID- 27883992
TI  - Precuneal Thickness and Depression in Parkinson Disease.
AB  - BACKGROUND: Depression-related gray matter changes in Parkinson disease (PD)
      patients have been reported, although studies investigating cortical thickness in
      early-stage disease are lacking. OBJECTIVE: We aimed to evaluate cortical changes
      related to depression in early-stage PD patients with an extensive
      neuropsychological evaluation. METHODS: 17 PD patients and 22 healthy controls
      underwent a 1.5-T brain MR protocol, and voxel-wise differences in cortical
      thickness among patients with (n = 6) and without (n = 11) depression and
      controls were evaluated using FreeSurfer software. RESULTS: Cortical thickness
      was increased in the precuneus bilaterally in PD patients with depression
      compared to the other groups (number of vertices >100; p < 0.001, uncorrected)
      with a direct correlation with the Beck Depression Inventory score (p < 0.001,
      uncorrected). CONCLUSION: Precuneal cortical thickening is evident in PD patients
      with mild-moderate depression even in the early stages of the disease. This
      finding may reflect the early involvement of this region in the development of PD
      related depression.

PMID- 27883993
TI  - Stimulation of the Nonneuronal Cholinergic System by Highly Diluted Acetylcholine
      in Keratinocytes.
AB  - The physiological effects of acetylcholine on keratinocytes depend on the
      presence of nicotinic and muscarinic receptors. The role of nonneuronal
      acetylcholine in keratinocytes could have important clinical implications for
      patients with various skin disorders such as nonhealing wounds. In order to
      evaluate the efficacy of highly diluted acetylcholine solutions obtained by
      sequential kinetic activation, we aimed to investigate the effects of these
      solutions on normal human keratinocytes. Two different concentrations (10 fg/mL
      and 1 pg/mL) and formulations (kinetically activated and nonkinetically
      activated) of acetylcholine were used to verify keratinocyte viability,
      proliferation, and migration and the intracellular pathways involved using MTT,
      crystal violet, wound healing, and Western blot compared to 147 ng/mL
      acetylcholine. The activated formulations (1 pg/mL and 10 fg/mL) revealed a
      significant capacity to increase migration, cell viability, and cell
      proliferation compared to 147 ng/mL acetylcholine, and these effects were more
      evident after a single administration. Sequential kinetic activation resulted in
      a statistically significant decrease in reactive oxygen species production
      accompanied by an increase in mitochondrial membrane potential and a decrease in
      oxygen consumption compared to 147 ng/mL acetylcholine. The M1 muscarinic
      receptor was involved in these effects. Finally, the involvement of ERK/mitogen
      activated protein kinases (MAPK) and KI67 confirmed the effectiveness of the
      single treatment on cell proliferation. The intracellular pathways of calcium
      were investigated as well. Our results indicate for the first time that highly
      diluted and kinetically activated acetylcholine seems to play an active role in
      an in vitro model of wound healing. Moreover, the administration of acetylcholine
      within the physiological range may not only be effective but is also likely to be
      safe.

PMID- 27883994
TI  - Monitoring Huntington's Disease Mortality across a 30-Year Period: Geographic and
      Temporal Patterns.
AB  - BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative
      condition characterized by chorea, dystonia, behavioral disturbances and
      cognitive decline. The aim of this study is to assess temporal and spatial
      changes on mortality attributable to HD over 30 years in Spain. METHODS: HD data
      were extracted from the nationwide mortality registry for the period 1984-2013.
      Annual and 5-year gender- and age-specific rates adjusted for the standard
      European population were calculated. Geographic analysis was performed by
      districts from 1999 through 2013, and then estimated standardized mortality
      ratios (SMRs) and smoothed SMRs. RESULTS: There were 1,556 HD-related deaths
      across the study period. An increasing trend in age-adjusted HD mortality was in
      evidence, specifically from 1994 through 1998. On a year-by-year basis, age
      adjusted mortality rates increased from 0.076 per 100,000 population in 1984 to
      0.157 in 2013. Geographical differences among districts were evident in specific
      areas and in the southwest of Spain with a significantly higher HD mortality
      risk. CONCLUSION: HD mortality rising trends in Spain might be attributable to
      improvements in diagnosis leading to a rise in prevalence. Geographical
      variability in HD mortality could be related to regional differences in disease
      prevalence, health-care disparities, or other factors which call for in-depth
      assessment in future studies.

PMID- 27883995
TI  - Natural Terpenes Influence the Activity of Antibiotics against Isolated
      Mycobacterium tuberculosis.
AB  - OBJECTIVE: In this study, we aimed to describe the influence of natural terpenes
      on the antimycobacterial activity of first-line tuberculostatic drugs against
      isolated Mycobacterium tuberculosis. MATERIALS AND METHODS: The natural terpenes
      used in this study were R-limonene, S-limonene, myrcene, sabinene, alpha-pinene,
      and beta-elemene. The values of the minimum inhibitory concentration (MIC) for
      these terpenes, as well as for combinations of terpenes with tuberculostatic
      antibiotics (ethambutol, isoniazid, and rifampicin), were determined using a tube
      log2 dilution method in the range of 125-0.059 ug/mL. RESULTS: S-limonene had a
      strong synergistic effect with all tested antibiotics (MIC decreased from 16 to
      0.475 ug/mL for ethambutol, from 16 to 0.237 ug/mL for rifampicin, and from 32 to
      0.475 ug/mL for isoniazid). Combinations of myrcene, R-limonene, beta-elemene,
      and sabinene with tuberculostatic antibiotics resulted in a decreased MIC of the
      antibiotics (from 3.9 to 0.475 ug/mL for ethambutol, from 15 to 0.475 ug/mL for
      isoniazid, and from 0.475 to 0.237 ug/mL for rifampicin) while combinations of
      alpha-pinene with ethambutol and isoniazid resulted in increased MIC values (from
      16 to 125 ug/mL for ethambutol, and from 32 to 125 ug/mL for isoniazid).
      Rifampicin had a synergistic increase in activity with all the tested compounds.
      CONCLUSIONS: Our study showed that terpenes enhance the activity of
      tuberculostatic antibiotics.

PMID- 27883996
TI  - Phototherapy with Narrow-Band UVB in Adult Guttate Psoriasis: Results and Patient
      Assessment.
AB  - BACKGROUND: Acute guttate psoriasis (AGP) is a distinctive clinical entity with
      good response to treatment with narrow-band ultraviolet B (NB-UVB). OBJECTIVE: To
      investigate the results of NB-UVB phototherapy in adult patients with adult
      guttate psoriasis. MATERIAL AND METHODS: We carried out a prospective, open, and
      observational study. Patients over 18 years with more than 5% of body surface
      area affected were included. The PASI was assessed prior to and after treatment.
      The follow-up period was 18 months. After treatment, patients completed a simple
      questionnaire to assess their overall impression of the treatment. RESULTS: The
      67 adult patients with AGP included in this study had an initial PASI of 8.55 (SD
      5.03). Patients were treated with a mean of 19.9 sessions (SD 13.5) and mean
      doses of 14 mJ/cm2 (SD 10.5). Of the 67 patients, 52 achieved PASI90 with 96.15%
      of PASI reduction, and of these, 46 (88%) maintained PASI90 during the 18 months
      of follow-up. Patients were very satisfied with the treatment. DISCUSSION: AGP is
      a defined clinical entity with a variable course. Phototherapy with NB-UVB
      appears to be a very good option for treatment of AGP because of the good results
      obtained and patient satisfaction.

PMID- 27883997
TI  - CBT4BN: A Randomized Controlled Trial of Online Chat and Face-to-Face Group
      Therapy for Bulimia Nervosa.
AB  - OBJECTIVE: Although cognitive-behavioral therapy (CBT) represents the first-line
      evidence-based psychotherapy for bulimia nervosa (BN), most individuals seeking
      treatment do not have access to this specialized intervention. We compared an
      Internet-based manualized version of CBT group therapy for BN conducted via a
      therapeutic chat group (CBT4BN) to the same treatment conducted via a traditional
      face-to-face group therapy (CBTF2F). METHOD: In a two-site, randomized,
      controlled noninferiority trial, we tested the hypothesis that CBT4BN would not
      be inferior to CBTF2F. A total of 179 adult patients with BN (2.6% males)
      received up to 16 sessions of group CBT over 20 weeks in either CBT4BN or CBTF2F,
      and outcomes were compared at the end of treatment and at the 12-month follow-up.
      RESULTS: At the end of treatment, CBT4BN was inferior to CBTF2F in producing
      abstinence from binge eating and purging. However, by the 12-month follow-up,
      CBT4BN was mostly not inferior to CBTF2F. Participants in the CBT4BN condition,
      but not CBTF2F, continued to reduce their binge-eating and purging frequency from
      the end of treatment to the 12-month follow-up. CONCLUSIONS: CBT delivered online
      in a group chat format appears to be an efficacious treatment for BN, although
      the trajectory of recovery may be slower than face-to-face group therapy. Online
      chat groups may increase accessibility of treatment and represent a cost
      effective approach to service delivery. However, barriers in service delivery
      such as state-specific license and ethical guidelines for online therapists need
      to be addressed.

PMID- 27883998
TI  - The Non-Ergot Derived Dopamine Agonist Quinagolide as an Anti-Endometriotic
      Agent.
AB  - AIM: The study aimed to investigate the efficacy of a dopamine agonist,
      quinagolide, on experimentally induced endometriosis in a rat model. METHODS:
      Twenty female Wistar rats were used in this experiment. Endometriosis was
      surgically induced by transplantation of autologous endometrial tissue. A second
      laparotomy was performed 4 weeks after the first one to assess the pre-treatment
      implant volumes, and peritoneal lavage with saline solution was performed to
      assess the peritoneal cytokine levels. Rats were randomized to treatment with
      quinagolide or saline. At the end of the treatment period, a third laparotomy was
      performed to compare pre- and post-treatment implant volumes and cytokine levels
      within the groups. Implants were excised to compare glandular tissue (GT) and
      stromal tissue (ST) scores between the groups. RESULTS: In the quinagolide group,
      post-treatment volume was statistically significantly reduced compared with pre
      treatment volume (p = 0.01). There were significant decreases in interleukin-6
      (IL-6) and vascular endothelial growth factor (VEGF) levels in peritoneal fluid
      samples in quinagolide-treated rats when compared to pre-treatment levels (p =
      0.03 and p < 0.01). Histopathologically, both GT and ST scores were significantly
      lower in the quinagolide group compared to the control group (p = 0.01 and p =
      0.02). CONCLUSIONS: Quinagolide caused a significant regression in endometriotic
      implants and it also significantly reduced the levels of IL-6 and VEGF in
      peritoneal fluid.

PMID- 27884000
TI  - Epigenetic Interactions and the Brain-Body Communication.

PMID- 27883999
TI  - Low Prevalence of Nodules in Rheumatoid Arthritis Patients in Kuwait: A
      Description and a Comparison of Patients from the Kuwait Registry for Rheumatic
      Diseases.
AB  - OBJECTIVES: To describe the prevalence of rheumatoid nodules (RN) in patients
      with rheumatoid arthritis (RA) and to compare their features with those of
      patients without RN. SUBJECTS AND METHODS: Adult RA patients (n = 952) in the
      Kuwait Registry for Rheumatic Diseases from February 2013 to December 2015 were
      evaluated for RN. Demographic and serological features and disease activity and
      severity were obtained from the registry. RESULTS: Of the 952 RA patients, 22
      (2.3%) had RN and 930 (97.7%) did not. Age, sex, disease duration, smoking, and
      family history of an autoimmune rheumatic disease were similar. Obesity was more
      prevalent in the RN group, i.e. 11 (50%) vs. 326 (35.1%), p = 0.016. There was no
      difference in rheumatoid factor (RF) or anti-cyclic citrullinated peptide
      antibody positivity. Patients with RN had more sicca symptoms, i.e. 8 (36.4%) vs.
      152 (16.3%), p = 0.025, a higher mean score on the visual analogue scale pain (3
      +/- 2.9 vs. 2 +/- 2.7, p < 0.001), more tender joints (6.4 +/- 8.8 vs. 4.2 +/-
      7.2, p = 0.001), a higher patient global assessment of disease activity (3.3 +/-
      2.7 vs. 2.3 +/- 2.7, p < 0.001), and more deformities, i.e. 3 (13.6%) vs. 74
      (8%), p = 0.034. The mean health assessment questionnaire score in RN patients
      was 1.1 versus 0.9 in patients without RN (p = 0.08). Patients with RN had a low
      disease activity (means: disease activity score [DAS-28], 3.02; clinical disease
      activity index, 7.7; and simple disease activity index, 10.4), similar to the
      other group. While the rates of methotrexate treatment were comparable, biologic
      therapy was administered more in patients with RN (i.e. 15 [68.2%] vs. 478
      [51.4%], p < 0.001). CONCLUSION: In Kuwait, the prevalence of RN is low among RA
      patients. Patients with and without RN are similar in terms of demographics and
      serologic features, except for more obesity. However, patients with RN have more
      sicca symptoms, joint deformities, and painful and tender joints. Disease
      activity scores are low with more frequent biologic therapy.

PMID- 27884001
TI  - Effects of the Integrative Mind-Body Intervention on Depression, Sleep
      Disturbances and Plasma IL-6.

PMID- 27884002
TI  - Depression following Acute Coronary Syndrome: Time-Specific Interactions between
      Stressful Life Events, Social Support Deficits, and 5-HTTLPR.

PMID- 27884003
TI  - Alexithymia as a Moderator of Treatment Outcomes in a Randomized Controlled Trial
      on Brief Psychodynamic Interpersonal Psychotherapy for Patients with
      Multisomatoform Disorder.

PMID- 27884005
TI  - The Journal's Appreciation.

PMID- 27884004
TI  - Precapillary Pulmonary Hypertension and Sleep-Disordered Breathing: Is There a
      Link?
AB  - Among patients with sleep apnea the reported prevalence of precapillary pulmonary
      hypertension (PH) has varied largely, depending on patient selection, disease
      definition, and associated conditions, in particular chronic pulmonary disease.
      However, in the absence of comorbidities, PH seems to be rare in patients with
      sleep apnea. Conversely, sleep-related breathing disorders have been commonly
      found in patients with PH and they have been associated with an impaired quality
      of life. Since sleep-related breathing disorders may affect the pulmonary
      circulation and vice versa, patients with sleep-related breathing disorders
      should be evaluated for risk factors, symptoms and clinical signs of PH and right
      ventricular heart failure and patients with PH should be evaluated for sleep
      apnea. Therapeutic options for patients with sleep apnea and PH may include
      supplemental oxygen, drugs and positive pressure ventilation. Both nocturnal
      oxygen administration and acetazolamide have been shown to improve sleep apnea in
      patients with PH. In addition, oxygen therapy also improved exercise performance.
      Further studies are needed to corroborate the efficacy of these and other
      treatments.

PMID- 27884006
TI  - Current Psychosomatic Practice.
AB  - Psychosomatic research has advanced over the past decades in dealing with complex
      biopsychosocial phenomena and may provide new effective modalities of patient
      care. Among psychosocial variables affecting individual vulnerability, course,
      and outcome of any medical disease, the role of chronic stress (allostatic
      load/overload) has emerged as a crucial factor. Assessment strategies include the
      Diagnostic Criteria for Psychosomatic Research. They are presented here in an
      updated version based on insights derived from studies carried out so far and
      encompass allostatic overload, type A behavior, alexithymia, the spectrum of
      maladaptive illness behavior, demoralization, irritable mood, and somatic
      symptoms secondary to a psychiatric disorder. Macroanalysis is a helpful tool for
      identifying the relationships between biological and psychosocial variables and
      the individual targets for medical intervention. The personalized and holistic
      approach to the patient includes integration of medical and psychological
      therapies in all phases of illness. In this respect, the development of a new
      psychotherapeutic modality, Well-Being Therapy, seems to be promising. The growth
      of subspecialties, such as psychooncology and psychodermatology, drives towards
      the multidisciplinary organization of health care to overcome artificial
      boundaries. There have been major transformations in health care needs in the
      past decades. From psychosomatic medicine, a land of innovative hypotheses and
      trends, many indications for changes in the current practice of medicine are now
      at hand. The aim of this critical review is to outline current and potential
      clinical applications of psychosomatic methods.

PMID- 27884008
TI  - Left-Ventricular Plication Reduces Wall Stress and Cardiomyocyte Hypertrophy in a
      Rat Model of Ischemic Cardiomyopathy.
AB  - BACKGROUND: The indications of left-ventricular plication (LVP) are
      controversial, although several studies have reported favorable outcomes in heart
      failure patients. The aim of this study was to assess left-ventricular (LV) wall
      stress and myocardial remodeling after LVP in a rat model of myocardial
      infarction (MI). METHODS: Sixteen rats underwent LVP by excluding the LV anterior
      wall scar 4 weeks after ligation of the left anterior descending artery. After 4
      weeks, LV wall stress was assessed using transthoracic echocardiography and an LV
      catheter. Gene expression of the wall stress markers, atrial natriuretic factor
      (ANF) and brain natriuretic peptide (BNP), were evaluated via reverse
      transcription polymerase chain reaction. Cardiomyocyte area and myocardial
      fibrosis were also examined through histological examinations. These parameters
      were compared to those in 16 rats that underwent coronary artery ligation but not
      LVP. RESULTS: We noted that the LV end-diastolic dimension was smaller (9.9 +/-
      0.3 vs. 11.2 +/- 0.2 mm, p < 0.05) and fractional shortening was greater (25 +/-
      2 vs. 15 +/- 1%, p < 0.05) in LVP rats than in sham rats. Moreover, systolic wall
      stress was lower in LVP rats (71 +/- 7 vs. 111 +/- 9 * 103 dyn/cm2, p < 0.05).
      Myocardial ANF and BNP expression levels were lower in LVP rats (2.6 +/- 0.3 vs.
      4.4 +/- 0.5 and 1.0 +/- 0.1 vs. 1.5 +/- 0.2 arbitrary units, respectively; p <
      0.05). Cardiomyocyte area was significantly decreased in LVP rats (556 +/- 15 vs.
      670 +/- 28 MUm2, p = 0.003) and was correlated with LV wall stress (r = 0.669, p
      = 0.002). The reduction in myocardial fibrosis after LVP was not significant.
      CONCLUSION: LVP reduced LV wall stress and cardiomyocyte hypertrophy in a rat
      model of MI.

PMID- 27884009
TI  - Motivation for Psychological Treatment Predicts Favorable Outcomes in Multimodal
      Interdisciplinary Treatment for Chronic Somatoform Pain.

PMID- 27884010
TI  - Less Neutrophil Extracellular Trap Formation in Term Newborns than in Adults.
AB  - BACKGROUND: Newborns are prone to infections, which are independent predictors of
      neonatal mortality and morbidity. Neutrophil extracellular traps (NETs) are
      structures composed of chromatin and antimicrobial molecules that capture and
      kill pathogens. NETs may play an important role in the innate immune system and,
      thus, might be associated with impaired neonatal immune function. OBJECTIVES:
      This study aimed to compare NET formation between term neonates and healthy
      adults. We additionally investigated the effects of gestational age, birth
      weight, mode of delivery, gender, and perinatal infections. METHODS: We collected
      cord blood from 57 term infants (mean gestational age, 39.1 weeks) and 9 late
      preterm infants (35 weeks), and peripheral blood from 18 healthy adult donors.
      Neutrophils were isolated, and then NET formation was induced using three
      different stimulants: N-formylmethionine-leucyl-phenylalanine, phorbol 12
      myristate 13-acetate (PMA), or lipopolysaccharide. NETs were
      immunohistochemically stained and analyzed with regard to NET percentage and NET
      area. RESULTS: With all three stimuli, healthy term infants showed a lower NET
      percentage than the adult control group (p < 0.0001 each). The groups also
      differed in NET area, but the significance level was lower. Following PMA
      stimulation, we observed greater reductions in NET percentage and NET area in
      preterm than term infants. CONCLUSIONS: The lower NET formation observed in term
      infants compared to adults likely contributes to the reduced neonatal immune
      response. NET formation appeared to be even further decreased in late preterm
      neonates. There remains a need for further investigations of NET formation in
      more immature preterm infants.

PMID- 27884011
TI  - Gastroduodenal Lipomatosis in Familial Multiple Lipomatosis.
AB  - OBJECTIVE: To present a case of gastroduodenal lipomatosis associated with
      familial multiple lipomatosis (FML). CLINICAL PRESENTATION AND INTERVENTION: A 58
      year-old male presented with FML that manifested as multiple, painless,
      subcutaneous lipomas on his body; his mother had subcutaneous lipoma without a
      diagnosis of gastroduodenal lipomatosis. His lipid profile was normal. Abdominal
      computed tomography showed multiple, submucosal, polypoid lesions (of uniform
      density) of fat in the stomach and duodenum, and a small, similar lesion in the
      ileum. CONCLUSION: This case shows that gastrointestinal lipomatosis can manifest
      as FML.

PMID- 27884012
TI  - Gut Microbiota, Bacterial Translocation, and Interactions with Diet:
      Pathophysiological Links between Major Depressive Disorder and Non-Communicable
      Medical Comorbidities.
AB  - BACKGROUND: Persistent low-grade immune-inflammatory processes, oxidative and
      nitrosative stress (O&NS), and hypothalamic-pituitary-adrenal axis activation are
      integral to the pathophysiology of major depressive disorder (MDD). The
      microbiome, intestinal compositional changes, and resultant bacterial
      translocation add a new element to the bidirectional interactions of the gut
      brain axis; new evidence implicates these pathways in the patho-aetiology of MDD.
      In addition, abnormalities in the gut-brain axis are associated with several
      chronic non-communicable disorders, which frequently co-occur in individuals with
      MDD, including but not limited to irritable bowel syndrome (IBS), chronic fatigue
      syndrome (CFS), obesity, and type 2 diabetes mellitus (T2DM). METHODS: We
      searched the PubMed/MEDLINE database up until May 1, 2016 for studies which
      investigated intestinal dysbiosis and bacterial translocation (the 'leaky gut')
      in the pathophysiology of MDD and co-occurring somatic comorbidities with an
      emphasis on IBS, CFS, obesity, and T2DM. RESULTS: The composition of the gut
      microbiota is influenced by several genetic and environmental factors (e.g.
      diet). Several lines of evidence indicate that gut-microbiota-diet interactions
      play a significant pathophysiological role in MDD and related medical
      comorbidities. Gut dysbiosis and the leaky gut may influence several pathways
      implicated in the biology of MDD, including but not limited to immune activation,
      O&NS, and neuroplasticity cascades. However, methodological inconsistencies and
      limitations limit comparisons across studies. CONCLUSIONS: Intestinal dysbiosis
      and the leaky gut may constitute a key pathophysiological link between MDD and
      its medical comorbidities. This emerging literature opens relevant preventative
      and therapeutic perspectives.

PMID- 27884013
TI  - Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in
      Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature,
      and Primary Insulin-Like Growth Factor-I Deficiency.
AB  - BACKGROUND/AIMS: On behalf of the Drug and Therapeutics, and Ethics Committees of
      the Pediatric Endocrine Society, we sought to update the guidelines published in
      2003 on the use of growth hormone (GH). Because idiopathic short stature (ISS)
      remains a controversial indication, and diagnostic challenges often blur the
      distinction between ISS, GH deficiency (GHD), and primary IGF-I deficiency
      (PIGFD), we focused on these three diagnoses, thereby adding recombinant IGF-I
      therapy to the GH guidelines for the first time. METHODS: This guideline was
      developed following the GRADE approach (Grading of Recommendations, Assessment,
      Development, and Evaluation). RESULTS: This guideline provides recommendations
      for the clinical management of children and adolescents with growth failure from
      GHD, ISS, or PIGFD using the best available evidence. CONCLUSION: The taskforce
      suggests that the recommendations be applied in clinical practice with
      consideration of the evolving literature and the risks and benefits to each
      individual patient. In many instances, careful review highlights areas that need
      further research.

PMID- 27884014
TI  - Biology, Social Environment, and Personalized Medicine.

PMID- 27884015
TI  - Joseph-Frederic-Benoit Charriere - How to Explain His Success as One of the Most
      Famous Surgical Instrument Makers Regarding His Life from Childhood to Death.
AB  - INTRODUCTION: We use the name 'Charriere' every day as a unit of measurement.
      This article explains his success as one of the most famous instrument makers who
      ever lived. MATERIALS AND METHODS: A review of the literature was completed using
      PubMed. Additionally, material of historical sources like the museum of Bulle was
      used. RESULTS: Joseph-Frederic-Benoit Charriere was born in Switzerland in 1803.
      At the age of 13, he moved to Paris and learned the profession of a cutler. In
      1820, he took over the workshop of his teacher Vincent. Dupuytren was one of the
      most important people in Charriere's professional life. Charriere specialized in
      the fabrication of surgical instruments of such high quality that he was very
      sought after by famous surgeons. In 1837, Charriere went to Sheffield, England,
      to learn more about working with metals and alloys. In 1851, he was inducted into
      the Legion of Honour. Charriere died in 1876 in Paris. CONCLUSIONS: The patronage
      of Dupuytren was a very important supporting factor in Charriere's professional
      life, but mainly his great courage, the willingness to learn from others, his
      creativity and technical fantasy and his curiosity and broad interest in a lot of
      different fields explain his unmatched professional success.

PMID- 27884020
TI  - ?

PMID- 27884019
TI  - ?

PMID- 27884016
TI  - Expression profiling of budding cells in colorectal cancer reveals an EMT-like
      phenotype and molecular subtype switching.
AB  - BACKGROUND: Tumour budding, described as the presence of single cells or small
      clusters of up to five tumour cells at the invasive margin, is established as a
      prognostic marker in colorectal carcinoma. In the present study, we aimed to
      investigate the molecular signature of tumour budding cells and the corresponding
      tumour bulk. METHODS: Tumour bulk and budding areas were microdissected and
      processed for RNA-sequencing. As little RNA was obtained from budding cells, a
      special low-input mRNA library preparation protocol was used. Gene expression
      profiles of budding as compared with tumour bulk were investigated for
      established EMT signatures, consensus molecular subtype (CMS), gene set
      enrichment and pathway analysis. RESULTS: A total of 296 genes were
      differentially expressed with an FDR <0.05 and a twofold change between tumour
      bulk and budding regions. Genes that were upregulated in the budding signature
      were mainly involved in cell migration and survival while downregulated genes
      were important for cell proliferation. Supervised clustering according to an
      established EMT gene signature categorised budding regions as EMT-positive,
      whereas tumour bulk was considered EMT-negative. Furthermore, a shift from CMS2
      (epithelial) to CMS4 (mesenchymal) was observed as tumour cells transit from the
      tumour bulk to the budding regions. CONCLUSIONS: Tumour budding regions are
      characterised by a phenotype switch compared with the tumour bulk, involving the
      acquisition of migratory characteristics and a decrease in cell proliferation. In
      particular, most tumour budding signatures were EMT-positive and switched from an
      epithelial subtype (CMS2) in the tumour bulk to a mesenchymal subtype (CMS4) in
      budding cells.

PMID- 27884017
TI  - The p53 family orchestrates the regulation of metabolism: physiological
      regulation and implications for cancer therapy.
AB  - The p53 family of transcription factors is essential to counteract tumour
      formation and progression. Although previously this was exclusively associated
      with the ability of the p53 family to induce cell cycle arrest and apoptosis, an
      increasing number of reports have now indisputably demonstrated that the tumour
      suppressive functions of the p53 family members also rely on their ability to
      control and regulate cellular metabolism and maintain cellular oxidative
      homeostasis. Here, we review how each p53 family member, including p63 and p73,
      controls metabolic pathways in physiological conditions, and how these mechanisms
      could be exploited to provide anticancer therapeutic opportunities.

PMID- 27884021
TI  - ?

PMID- 27884022
TI  - ?

PMID- 27884018
TI  - Blood transfusion during radical chemo-radiotherapy does not reduce tumour
      hypoxia in squamous cell cancer of the head and neck.
AB  - BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC)
      undergoing radical chemo-radiation (CRT) frequently receive transfusion with
      packed red cells (PRCT) during radiotherapy on the basis that PRCT increases
      tumour oxygenation and overcomes hypoxia-induced radio-resistance. This is likely
      to be a significant oversimplification given the fact that tumour hypoxia is the
      result of several intrinsic and extrinsic factors, including many that are not
      directly related to serum haemoglobin (Hb). Therefore, we have studied the effect
      of PRCT on tumour oxygenation in a prospective cohort of patients who developed
      low Hb during radical CRT for HNSCC. METHODS: This was a prospective study of 20
      patients with HNSCC receiving radical CRT undergoing PRCT for Hb<11.5 g dl-1.
      Patients underwent pretransfusion and posttransfusion intrinsic susceptibility
      weighted (SWI) MRI and dynamic contrast-enhanced (DCE) MRI. Blood samples were
      obtained at the time of MRI scanning and two further time points for measuring Hb
      and a panel of serum cytokine markers of tumour hypoxia. 3D T2* and Ktrans maps
      were calculated from the MRI data for primary tumours and cervical lymph node
      metastases. RESULTS: PRCT produced no change (11 patients) or reduced (1 patient)
      T2* (tumour oxygenation) in 12 of the 16 (75%) evaluable primary tumours. Three
      of the four patients with improved tumour oxygenation progressed or had partial
      response following treatment completion. There were variable changes in Ktrans
      (tumour perfusion or vessel permeability) following PRCT that were of small
      magnitude for most tumours. Pre- and Post-PRCT levels of measured cytokines were
      not significantly different. CONCLUSIONS: This study suggests that PRCT during
      radical CRT for HNSCC does not improve tumour oxygenation. Therefore, oncologists
      should consider changing practice according to NICE and American Association of
      Blood Banks guidelines on PRCT for anaemia.

PMID- 27884023
TI  - ?

PMID- 27884024
TI  - ?

PMID- 27884025
TI  - ?

PMID- 27884026
TI  - [Awake video laryngoscopy - an alternative to awake fiberoptic intubation?]
AB  - INTRODUCTION: Awake video laryngoscopy is a novel option in airway management
      that is drawing more and more attention as an alternative to awake endoscopic
      guided intubation.Main issues: Intubation under preserved spontaneous breathing
      is the safest method to secure the expected difficult airway. In direct
      comparisons to awake flexible endoscopic intubation, awake video laryngoscopy
      achieves satisfactory intubation times and a high acceptance of patients and
      anesthesiologists. Specific cases, in particular very limited mouth opening or
      sub-glottic masses, require awake flexible endoscopic intubation. Sufficient
      topical anesthesia and a sophisticated sedation protocol are prerequisites for
      successful awake video laryngoscopy. CONCLUSION: Awake video laryngoscopy cannot
      fully replace flexible endoscopic intubation. It is a useful option, but it must
      be considered that this technique is not suitable for all types of airways,
      patients or even anesthesiologists. Expertise and adequate practice is mandatory
      for both techniques. Careful planning, an appropriate blade design and a high
      expertise in video laryngoscopy are crucial for a successful intubation.

PMID- 27884027
TI  - [Transfer of critically ill patients between hospitals - fundamentals and
      requirements].
AB  - Due to the increasingly changed clinical landscape, which leads to a reduction of
      clinical facilities in rural regions. This also leads to a centralized clinical
      care, in addition to limited care options in the periphery. Therefore the
      interhospital transfer is becoming increasingly important. Specialized centers
      have become more and more important through this centralization of clinical care.
      Not only the number of transports, but also the transport distances have steadily
      increased in recent years. It is necessary to differentiate centripetal
      transports into the centers of the maximum and centrifugal transports back to
      peripheral clinics, weaning devices or rehabilitation facilities. Especially in
      the case of the latter, the number of patients still to be transported under
      intensive medical conditions has clearly increased.

PMID- 27884028
TI  - ?

PMID- 27884029
TI  - [Preclinical birth of an extremely premature infant - a case report].
AB  - Obstetrical emergencies requiring emergency medical service are very rare. An
      extremely premature birth in a preclinical setting is certainly exceptional. In
      the following case report, the emergency medical team was unexpectedly faced with
      the home birth of a fetus at the 23rd week of gestation. Prematurity at the edge
      of viability poses a challenge to first care, equipment, infrastructure,
      expertise and clinical ethics. To the authors' knowledge, there is no comparable
      case report published so far.

PMID- 27884030
TI  - ?

PMID- 27884031
TI  - [Postoperative acute kidney injury: confounder or causal link for surgical
      outcome?]
AB  - Demographic change and increase of complexity of diagnostic and surgical
      procedures lead to an increasing relevance of acute kidney injury as
      postoperative complication. Postoperative acute kidney injury is associated with
      higher mortality, morbidity and treatment costs. It has not yet been
      unequivocally proven that postoperative acute kidney injury is in fact causally
      linked with worse treatment outcome in surgical patients. This article aims to
      give an overview of the phenomenon postoperative acute kidney injury, to discuss
      problems of demonstrating causal relations in biomedical research, and to present
      arguments for and against the hypothesis that postoperative acute kidney injury
      is causally linked to worse surgical outcome.

PMID- 27884032
TI  - [Acute kidney injury - remote ischaemic preconditioning: a nephroprotective
      strategy?]
AB  - Acute kidney injury is a common and serious complication with a huge impact on
      morbidity and short- as well as long-term mortality. Sepsis and major surgeries,
      especially cardiac surgery, are the most common causes of acute kidney injury.
      Slight increases of serum-creatinine levels are associated with adverse outcomes
      highlighting the relevance of the need for nephroprotective strategies to reduce
      the occurrence of acute kidney injury. Remote ischaemic preconditioning is an
      intervention consisting of brief episodes of ischaemia and reperfusion at a
      remote site before subsequent ischaemic insults occur. This simple and
      uncomplicated method may offer an effective nephroprotective strategy.

PMID- 27884033
TI  - [Acute kidney injury - status of biomarkers in perioperative and critically ill
      patients].
AB  - Acute kidney injury (AKI) impairs short- and long-term prognosis of affected
      patients even in case of apparantly mild course and 'full' recovery as measured
      by follow-up serum creatinine concentrations. Late or none intervention worsens
      prognosis. However, there are modifiable factors potentially contributing to
      preserved long-term renal function. Effective treatment is multifactorial and
      includes identification and reversal of AKI etiology and generation of a
      (micro)environment for optimal renal recovery. Available treatment options for
      AKI in perioperative and critically ill patients will be discussed in the setting
      of novel kidney biomarkers.

PMID- 27884034
TI  - ?

PMID- 27884035
TI  - ?

PMID- 27884036
TI  - ?

PMID- 27884037
TI  - ?

PMID- 27884038
TI  - Is There an Association between Body Mass Index and Cervical Length? Implications
      for Obesity and Cervical Length Management in Pregnancy.
AB  - Objective Obesity and cervical insufficiency are leading causes of morbidity in
      pregnancy. We assess the relationship between maternal body mass index (BMI) and
      second-trimester cervical length. Methods A secondary analysis of a nested case
      control study of women with singleton gestations enrolled from 2006 to 2008. The
      primary exposure was first-trimester BMI, categorized per World Health
      Organization criteria: normal (18.5 to <= 25 kg/m2), overweight (25 to <= 30
      kg/m2), and obese (> 30 kg/m2). The primary outcome was cervical length > 75th
      percentile. Results Among 391 pregnant women observed, the median cervical length
      was 3.6 cm, and the median BMI was 24.8 kg/m2. In multivariable analyses, after
      adjusting for BMI, age, race, parity, smoking, and gestational age at delivery,
      women who were overweight (adjusted odds ratio [AOR]: 2.18; 95% CI: 1.20-3.96)
      and obese (AOR: 2.83; 95% CI: 1.47-5.43) were more than two times more likely to
      have a cervical length > 75th percentile. When cervical length and BMI were
      assessed linearly, for each 1.0 kg/m2 increase in BMI, cervical length increased
      by 0.25 mm. These results were robust to utilizing different cutoffs of cervical
      length and pre-pregnancy BMI. Conclusion This study demonstrates a relationship
      between BMI and cervical length suggesting that obesity may be associated with
      longer cervical length. These results will need to be replicated in larger
      cohorts undergoing universal cervical length assessment.

PMID- 27884039
TI  - Clarifying the Links of Conscientiousness With Internalizing and Externalizing
      Psychopathology.
AB  - OBJECTIVE: Although Conscientiousness/disinhibition plays a substantial role in
      internalizing and externalizing psychopathology, the underlying mechanisms are
      not well understood. We aim to clarify facet-level associations and to examine
      whether (a) impairment mediates the link of Conscientiousness with internalizing
      and externalizing symptoms, and (b) demoralization (assessed via Neuroticism)
      accounts for their associations. METHOD: A total of 450 participants (Mage  = 42;
      primarily female and Caucasian) who reported current/recent psychiatric treatment
      completed two measures of domain- and facet-level traits (i.e., NEO-PI-3, PID-5),
      as well as interview measures of impairment and disorders. Correlation,
      regression, and mediation analyses were conducted. RESULTS: Internalizing
      disorders (and particularly, the distress disorders) were uniquely associated
      with facets related to low self-efficacy, whereas externalizing disorders were
      uniquely associated with risk-taking and disregarding rules. For the
      internalizing disorders only, these associations were reduced after accounting
      for Neuroticism, though associations with distress disorders remained
      significant. Impairment mediated the link between Conscientiousness and symptoms
      for internalizing disorders, but not consistently for externalizing disorders.
      CONCLUSIONS: The internalizing and externalizing disorders are associated with
      Conscientiousness due to different facet-level content. Demoralization and
      impairment both contribute to the link between internalizing disorders and
      Conscientiousness, whereas neither process accounts substantially for the
      relation of externalizing disorders with Conscientiousness.

PMID- 27884040
TI  - Personality Makes a Difference: Attachment Orientation Moderates Theory of
      Planned Behavior Prediction of Cardiac Medication Adherence.
AB  - OBJECTIVE: To achieve a comprehensive understanding of patients' adherence to
      medication following acute coronary syndrome (ACS), we assessed the possible
      moderating role played by attachment orientation on the effects of attitudes,
      subjective norms, and perceived behavioral control (PBC), as derived from the
      Theory of Planned Behavior (TPB; Ajzen, 1991), on intention and reported
      adherence. METHOD: A prospective longitudinal design was employed. During
      hospitalization, ACS male patients (N = 106) completed a set of self-report
      questionnaires including sociodemographic variables, attachment orientation, and
      measures of TPB constructs. Six months post-discharge, 90 participants completed
      a questionnaire measuring adherence to medication. RESULTS: Attachment
      orientations moderated some of the predictions of the TPB model. PBC predicted
      intention and reported adherence, but these associations were found to be
      significant only among individuals with lower, as opposed to higher, attachment
      anxiety. The association between attitudes and intention was stronger among
      individuals with higher, as opposed to lower, attachment anxiety. Only among
      individuals with higher attachment avoidance, subjective norms were negatively
      associated with intention to take medication. CONCLUSIONS: Cognitive variables
      appear to explain both adherence intention and behavior, but differently,
      depending on individuals' attachment orientations. Integrating personality and
      cognitive models may prove effective in understanding patients' health behaviors.

PMID- 27884041
TI  - Follow-up strategies for patients treated for non-metastatic colorectal cancer.
AB  - BACKGROUND: It is common clinical practice to follow patients with colorectal
      cancer (CRC) for several years following their curative surgery or adjuvant
      therapy, or both. Despite this widespread practice, there is considerable
      controversy about how often patients should be seen, what tests should be
      performed, and whether these varying strategies have any significant impact on
      patient outcomes. This is the second update of a Cochrane Review first published
      in 2002 and first updated in 2007. OBJECTIVES: To assess the effects of intensive
      follow-up for patients with non-metastatic colorectal cancer treated with
      curative intent. SEARCH METHODS: For this update, we searched CENTRAL (2016,
      Issue 3), MEDLINE (1950 to May 20th, 2016), Embase (1974 to May 20th, 2016),
      CINAHL (1981 to May 20th, 2016), and Science Citation Index (1900 to May 20th,
      2016). We also searched reference lists of articles, and handsearched the
      Proceedings of the American Society for Radiation Oncology (2011 to 2014). In
      addition, we searched the following trials registries (May 20th, 2016):
      ClinicalTrials.gov and the World Health Organization International Clinical
      Trials Registry Platform. We further contacted study authors. No language or
      publication restrictions were applied to the search strategies. SELECTION
      CRITERIA: We included only randomised controlled trials comparing different
      follow-up strategies for participants with non-metastatic CRC treated with
      curative intent. DATA COLLECTION AND ANALYSIS: Two authors independently
      determined trial eligibility, performed data extraction, and assessed
      methodological quality. MAIN RESULTS: We studied 5403 participants enrolled in 15
      studies. (We included two new studies in this second update.) Although the
      studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon
      led) and "intensity" of follow-up, there was very little inconsistency in the
      results.Overall survival: we found no evidence of a statistical effect with
      intensive follow-up (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.78 to
      1.02; I2 = 4%; P = 0.41; high-quality evidence). There were 1098 deaths among
      4786 participants enrolled in 12 studies.Colorectal cancer-specific survival:
      this did not differ with intensive follow-up (HR 0.93, 95% CI 0.78 to 1.12; I2 =
      0%; P = 0.45; moderate-quality evidence). There were 432 colorectal cancer deaths
      among 3769 participants enrolled in seven studies.Relapse-free survival: we found
      no statistical evidence of effect with intensive follow-up (HR 1.03, 95% CI 0.90
      to 1.18; I2 = 5%; P = 0.39; moderate-quality evidence). There were 1416 relapses
      among 5253 participants enrolled in 14 studies.Salvage surgery with curative
      intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98,
      95% CI 1.53 to 2.56; I2 = 31%; P = 0.14; high-quality evidence). There were 457
      episodes of salvage surgery in 5157 participants enrolled in 13 studies.Interval
      (symptomatic) recurrences: these were less frequent with intensive follow-up (RR
      0.59, 95% CI 0.41 to 0.86; I2 = 66%; P = 0.007; moderate-quality evidence). Three
      hundred and seventy-six interval recurrences were reported in 3933 participants
      enrolled in seven studies.Intensive follow-up did not appear to affect quality of
      life, anxiety, nor depression (reported in three studies).Harms from
      colonoscopies did not differ with intensive follow-up (RR 2.08, 95% CI 0.11 to
      40.17; moderate-quality evidence). In two studies, there were seven colonoscopic
      complications in 2112 colonoscopies. AUTHORS' CONCLUSIONS: The results of our
      review suggest that there is no overall survival benefit for intensifying the
      follow-up of patients after curative surgery for colorectal cancer. Although more
      participants were treated with salvage surgery with curative intent in the
      intensive follow-up group, this was not associated with improved survival. Harms
      related to intensive follow-up and salvage therapy were not well reported.

PMID- 27884042
TI  - Valproate for schizophrenia.
AB  - BACKGROUND: Many people with schizophrenia do not achieve a satisfactory
      treatment response with ordinary antipsychotic drug treatment. In these cases,
      various add-on medications are used, and valproate is one of these. OBJECTIVES:
      To examine whether:1. valproate alone is an effective treatment for schizophrenia
      and schizoaffective psychoses; and2. valproate augmentation of antipsychotic
      medication is an effective treatment for the same illnesses. SEARCH METHODS: We
      searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (July
      2002; February 2007; July 2012; March 04, 2016). We also contacted pharmaceutical
      companies and authors of relevant studies in order to identify further trials.
      SELECTION CRITERIA: We included all randomised controlled trials comparing
      valproate to antipsychotics or to placebo (or no intervention), whether as the
      sole agent or as an adjunct to antipsychotic medication for the treatment of
      people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND
      ANALYSIS: We independently inspected citations and, where possible, abstracts,
      ordered papers, and re-inspected and quality-assessed these. At least two review
      authors independently extracted data. We analysed dichotomous data using risk
      ratio (RR) and its 95% confidence intervals (CI). We analysed continuous data
      using mean differences (MD) and their 95% CI. We assessed risk of bias for
      included studies and used GRADE (Grading of Recommendations Assessment,
      Development and Evaluation) to create a 'Summary of findings' table. MAIN
      RESULTS: The 2012 update search identified 19 further relevant studies, most of
      which were from China. Thus the review currently includes 26 studies with a total
      of 2184 participants. All trials examined the effectiveness of valproate as an
      adjunct to antipsychotics. With the exception of two studies, the studies were
      small, the participants and personnel were not blinded (neither was outcome
      assessment), and most were short-term and incompletely reported.For this update
      we prespecified seven main outcomes of interest: clinical response (clinically
      significant response, aggression/agitation), leaving the study early
      (acceptability of treatment, overall tolerability), adverse events (sedation,
      weight gain) and quality of life.Adding valproate to antipsychotic treatment
      resulted in more clinically significant response than adding placebo to
      antipsychotic drugs (14 RCTs, n = 1049, RR 1.31, 95% CI 1.16 to 1.47, I2 = 12%,
      low-quality evidence). However, this effect was removed after excluding open RCTs
      in a sensitivity analysis. In terms of acceptability of treatment (measured by
      the number of participants leaving the study early due to any reason) valproate
      was just as acceptable as placebo (11 RCTs, n = 951, RR 0.76, 95% CI 0.47 to
      1.24, I2 = 55%). Also overall tolerability (measured by the number of
      participants leaving the study early for adverse events) between valproate and
      placebo was similar (6 RCTs, n = 974, RR 1.33, 95% CI 0.90 to 1.97, I2 =
      0).Participants in the valproate group were found to be less aggressive than the
      control group based on the Modified Overt Aggression Scale (3 RCTs, n = 186, MD 
      2.55, 95% CI -3.92 to -1.19, I2 = 82%, very low-quality evidence). Participants
      receiving valproate more frequently experienced sedation (8 RCTs, n = 770, RR
      1.38, 95% CI 1.07 to 1.79, I2 = 0, low-quality evidence) but were no more likely
      to gain weight than those receiving placebo (4 RCTs, n = 427, RR 1.17, 95% CI
      0.76 to 1.82, I2 = 0, low-quality evidence). No study reported on the important
      outcome of quality of life. AUTHORS' CONCLUSIONS: There is limited evidence,
      based on a number of trials, that the augmentation of antipsychotics with
      valproate may be effective for overall clinical response, and also for specific
      symptoms, especially in terms of excitement and aggression. However, this
      evidence was entirely based on open RCTs. Moreover, valproate was associated with
      a number of adverse events among which sedation and dizziness appeared
      significantly more frequently than in the control groups. Further randomised
      studies which are blinded are necessary before any clear recommendation can be
      made. Ideally these would focus on people with schizophrenia and aggression, on
      those with treatment-resistant forms of the illness and on those with
      schizoaffective disorders.

PMID- 27884044
TI  - Reply.

PMID- 27884043
TI  - Anti-inflammatory signaling during ex vivo liver perfusion improves the
      preservation of pig liver grafts before transplantation.

PMID- 27884046
TI  - Effect of Lycopene and Rosmarinic Acid on Gentamicin Induced Renal Cortical
      Oxidative Stress, Apoptosis, and Autophagy in Adult Male Albino Rat.
AB  - Gentamicin nephrotoxicity accounts for 10%-15% of all cases of acute renal
      failure. Several natural antioxidants were found to be effective against drug
      induced toxicity. The possible protective effects of lycopene (Lyc) and
      rosmarinic acid (RA) alone or combined on gentamicin (Gen) induced renal cortical
      oxidative stress, apoptosis, and autophagy were evaluated. Sixty-three rats were
      randomly divided into seven groups named: control, group II received RA 50
      mg/kg/day, group III received Lyc 4 mg/kg/day, group IV received Gen 100
      mg/kg/day, group V (RA + Gen), group VI (Lyc + Gen), and group VII (RA + Lyc +
      Gen). At the end of the experiment, kidney functions were estimated then the
      kidneys were sampled for histopathological, immunohistochemistry, and biochemical
      studies. Administration of rosmarinic acid and lycopene decreased elevated serum
      creatinine, blood urea nitrogen, renal malondialdehyde and immunoexpression of
      the proapoptotic protein (Bax), autophagic marker protein (LC3/B), and inducible
      nitric oxide synthase (iNOS) induced by gentamicin. They increased reduced
      glutathione, glutathione peroxidase, superoxide dismutase, and immunoexpression
      of the antiapoptotic protein (Bcl2). They also improved the histopathological
      changes induced by gentamicin. The combination therapy of rosmarinic acid and
      lycopene shows better protective effects than the corresponding monotherapy. Anat
      Rec, 300:1137-1149, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27884045
TI  - Retinoic acid signaling regulates Krt5 and Krt14 independently of stem cell
      markers in submandibular salivary gland epithelium.
AB  - BACKGROUND: Retinoic acid (RA), the active metabolite of vitamin A, has been
      demonstrated to be important for growth and branching morphogenesis of mammalian
      embryonic salivary gland epithelium. However, it is not known whether RA
      functions directly within epithelial cells or in associated tissues that
      influence morphogenesis of salivary epithelium. Moreover, downstream targets of
      RA regulation have not been identified. RESULTS: Here, we show that canonical RA
      signaling occurs in multiple tissues of embryonic mouse salivary glands,
      including epithelium, associated parasympathetic ganglion neurons, and
      nonneuronal mesenchyme. By culturing epithelium explants in isolation from other
      tissues, we demonstrate that RA influences epithelium morphogenesis by direct
      action in that tissue. Moreover, we demonstrate that inhibition of RA signaling
      represses cell proliferation and expression of FGF10 signaling targets, and
      upregulates expression of basal epithelial keratins Krt5 and Krt14. Importantly,
      we show that the stem cell gene Kit is regulated inversely from Krt5/Krt14 by RA
      signaling. CONCLUSIONS: RA regulates Krt5 and Krt14 expression independently of
      stem cell character in developing salivary epithelium. RA, or chemical inhibitors
      of RA signaling, could potentially be used for modulating growth and
      differentiation of epithelial stem cells for the purpose of re-populating damaged
      glands or generating bioengineered organs. Developmental Dynamics 246:135-147,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27884047
TI  - Childhood obesity prevention cluster randomized trial for Hispanic families:
      outcomes of the healthy families study.
AB  - BACKGROUND: Obesity prevalence is disproportionately high among Hispanic
      children. OBJECTIVES: The Healthy Families Study assessed the efficacy of a
      culturally targeted, family-based weight gain prevention intervention for
      Hispanic immigrant families with children ages 5-7 years. METHODS: The study used
      a two-group, cluster randomized trial design, assigning 136 families (clusters)
      to the active intervention (weight gain prevention) and 136 families to attention
      control (oral health). The active intervention included a 4-month intensive phase
      (eight classes) and an 8-month reinforcement phase (monthly mail/telephone
      contact). Children's body mass index z-score (BMI-Z) was the primary outcome.
      RESULTS: The BMI-Z growth rate of the active intervention group did not differ
      from the attention control group at short-term follow-up (median 6 months; 168
      families, 206 children) or long-term follow-up (median 16 months; 142 families,
      169 children). Dose response analyses indicated a slower increase in BMI-Z at
      short term among overweight/obese children who attended more intervention
      classes. Moderate physical activity on weekends increased at short term. Weekend
      screen time decreased at short term among those attending at least one class
      session. CONCLUSION: Low class attendance likely impacted intention-to-treat
      results. Future interventions targeting this population should test innovative
      strategies to maximize intervention engagement to produce and sustain effects on
      weight gain prevention.

PMID- 27884048
TI  - MicroRNA-142 is a multifaceted regulator in organogenesis, homeostasis, and
      disease.
AB  - Over the past decade, microRNA-142 (miR-142) is emerging as a major regulator of
      cell fate decision in the hematopoietic system. However, miR-142 is expressed in
      many other tissues, and recent evidence suggests that it may play a more
      pleiotropic role during embryonic development. In addition, miR-142 has been
      shown to play important functions in disease. miR-142 displays a functional role
      in cancer, virus infection, inflammation, and immune tolerance. Both a guide
      strand (miR-142-3p) and passenger strand (miR-142-5p) are generated from the miR
      142 hairpin. miR-142-3p and -5p display overlapping but also independent target
      genes. Loss of function mouse models (genetrap, global knock out [KO], and
      conditional KO) have been reported and support the important role of miR-142 in
      different biological processes. This review will summarize the abundant
      literature already available for miR-142 and will lay the foundation for future
      works on this important microRNA. Developmental Dynamics 246:285-290, 2017. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27884049
TI  - Copper toxicity response influences mesotrophic Synechococcus community
      structure.
AB  - Picocyanobacteria from the genus Synechococcus are ubiquitous in ocean waters.
      Their phylogenetic and genomic diversity suggests ecological niche
      differentiation, but the selective forces influencing this are not well defined.
      Marine picocyanobacteria are sensitive to Cu toxicity, so adaptations to this
      stress could represent a selective force within, and between, 'species', also
      known as clades. Here, we compared Cu stress responses in cultures and natural
      populations of marine Synechococcus from two co-occurring major mesotrophic
      clades (I and IV). Using custom microarrays and proteomics to characterize
      expression responses to Cu in the lab and field, we found evidence for a general
      stress regulon in marine Synechococcus. However, the two clades also exhibited
      distinct responses to copper. The Clade I representative induced expression of
      genomic island genes in cultures and Southern California Bight populations, while
      the Clade IV representative downregulated Fe-limitation proteins. Copper
      incubation experiments suggest that Clade IV populations may harbour stress
      tolerant subgroups, and thus fitness tradeoffs may govern Cu-tolerant strain
      distributions. This work demonstrates that Synechococcus has distinct adaptive
      strategies to deal with Cu toxicity at both the clade and subclade level,
      implying that metal toxicity and stress response adaptations represent an
      important selective force for influencing diversity within marine Synechococcus
      populations.

PMID- 27884050
TI  - Taking the sweetness out of the 'Share a Coke' marketing campaign: the influence
      of personalized labelling on elementary school children's bottled drink choices.
AB  - BACKGROUND: Drink personalization (featuring names on bottle labels) has been
      used by soft drink companies to make their drinks attractive to children,
      potentially increasing consumption. To date, no publically available research has
      evaluated the influence of personalization on children's drink choices.
      OBJECTIVES: To determine (i) whether personalizing bottled drinks influences
      children's drink choices; (ii) whether it is comparably effective in promoting
      healthy and unhealthy drinks and (iii) whether drink choices are affected by self
      esteem, body mass index and parental factors. METHODS: Children aged 8-13 years
      (N = 404) were randomly assigned to one of three drink labeling conditions: Prime
      Healthy, Prime Unhealthy and Control. All participants selected one beverage from
      12 options, comprising six healthy and unhealthy drinks. RESULTS: Personalizing
      healthy drinks increased choice of healthy drinks (OR, 2.21; 95% CI, 1.24-4.00),
      and personalizing unhealthy drinks reduced choice of healthy drinks (OR, 0.35;
      95% CI, 0.15-.0.75). Higher self-esteem predicted choosing own-named drinks (OR =
      1.08, 95% CI, 1.00-1.18; p = .049). CONCLUSIONS: Children's drink choices are
      influenced by personalizing drink bottles. Tighter regulation of this marketing
      strategy for soft drinks may reduce children choice of these drinks.
      Personalization may also be used to encourage children to choose healthy drinks.

PMID- 27884051
TI  - Unexpected interaction between deprotonated biliverdin and alcohols as studied by
      ESI-MS.

PMID- 27884052
TI  - Model Evaluation of Continuous Data Pharmacometric Models: Metrics and Graphics.
AB  - This article represents the first in a series of tutorials on model evaluation in
      nonlinear mixed effect models (NLMEMs), from the International Society of
      Pharmacometrics (ISoP) Model Evaluation Group. Numerous tools are available for
      evaluation of NLMEM, with a particular emphasis on visual assessment. This first
      basic tutorial focuses on presenting graphical evaluation tools of NLMEM for
      continuous data. It illustrates graphs for correct or misspecified models,
      discusses their pros and cons, and recalls the definition of metrics used.

PMID- 27884054
TI  - Morphoregulatory pathways in prostate ductal development.
AB  - The mouse prostate is a male sex-accessory gland comprised of a branched ductal
      network arranged into three separate bilateral lobes: the anterior, dorsolateral,
      and ventral lobes. Prostate ductal development is the primary morphogenetic event
      in prostate development and requires a complex regulation of spatiotemporal
      factors. This review provides an overview of prostate development and the major
      genetic regulators and signaling pathways involved. To identify new areas for
      further study, we briefly highlight the likely important, but relatively
      understudied, role of the extracellular matrix (ECM). Finally, we point out the
      potential importance of the ECM in influencing the behavior and prognosis of
      prostate cancer. Developmental Dynamics 246:89-99, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27884053
TI  - Disability in patients with end-stage liver disease: Results from the functional
      assessment in liver transplantation study.
AB  - Cirrhosis leads to sarcopenia and functional decline that can severely impact
      one's ability to function at home and in society. Self-reported disability scales
      to quantify disability-Activities of Daily Living (ADL) and Instrumental
      Activities of Daily Living (IADL)-are validated to predict mortality in older
      adults. To evaluate disability in liver transplantation (LT) candidates and
      quantify its impact on outcomes, consecutive outpatients >=18 years listed for LT
      with laboratory Model for End-Stage Liver Disease scores of >=12 at a single high
      volume US LT center were assessed for ADLs and IADLs during clinic visits.
      Multivariate competing risk models explored the effect of disabilities on wait
      list mortality (death or delisting for illness). Of 458 patients, 36% were women,
      median (interquartile range [IQR]) age was 60 years (IQR, 54-64 years), and
      initial Model for End-Stage Liver Disease-Sodium (MELD-Na) was 17 (IQR 14-20). At
      first visit, 31% had lost >= 1 ADL, and 40% had lost >= 1 IADL. The most
      prevalent ADL deficits lost were continence (22%), dressing (12%), and
      transferring (11%); the most prevalent IADLs lost were shopping (28%), food
      preparation (23%), and medication management (22%). After adjustment for age,
      MELD-Na, and encephalopathy, dressing (subdistribution hazard ratio [SHR], 1.7;
      95% confidence interval [CI], 1.0-2.8; P = 0.04), toileting (SHR, 1.9; 95% CI,
      1.1-3.5; P = 0.03), transferring (SHR, 1.9; 95% CI, 1.1-3.0; P = 0.009),
      housekeeping (SHR, 1.8; 95% CI, 1.2-3.0; P = 0.009), and laundry (SHR, 2.2; 95%
      CI, 1.3-3.5; P = 0.002) remained independent predictors of wait-list mortality.
      In conclusion, ADL/IADL deficits are common in LT candidates. LT candidates would
      benefit from chronic disease management programs developed to address the impact
      of cirrhosis on their daily lives. Liver Transplantation 23 292-298 2017 AASLD.

PMID- 27884055
TI  - The Association of Forefoot Varus Deformity with Patellofemoral Cartilage Damage
      in Older Adult Cadavers.
AB  - Forefoot alignment may contribute to patellofemoral joint (PFJ) osteoarthritis
      (OA) via its influence on the closed chain kinematics of the lower limb. The
      purpose of this cadaveric study was to investigate the relationship between
      forefoot varus and ipsilateral cartilage damage in the medial and lateral PFJ.
      Forefoot alignment measurements were obtained from the feet of 25 cadavers (n =
      50). Cartilage damage in the medial and lateral PFJ of each knee was scored using
      the Outerbridge scale. The relative odds of medial and lateral PFJ cartilage
      damage in limbs with forefoot varus and valgus were determined using logistic
      regression. The relationship between increasing varus alignment and increasing
      odds of medial and lateral PFJ cartilage damage was assessed. Of the 51% of limbs
      with forefoot varus, 91.3% had medial, and 78.3% had lateral PFJ cartilage
      damage, compared with 54.6% and 68.2% of those with forefoot valgus. The former
      also had 3.0 times (95% CI 1.2, 7.7) the odds of medial PFJ damage; no
      association was found with lateral damage (OR 1.4, 95% CI 0.7, 3.0). Feet in the
      highest tertile of varus alignment had 3.9 times (95% CI 10, 15.3, P = 0.058) the
      odds of medial PFJ damage as those in the lowest tertile. The results of this
      study suggest a relationship between forefoot varus and medial PFJ cartilage
      damage in older adults. As forefoot varus may be modified with foot orthoses,
      these findings indicate a potential role for orthoses in the treatment of medial
      PFJ OA. Anat Rec, 300:1032-1038, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27884056
TI  - Community assets and capabilities to recruit and retain GPs: the Community Apgar
      Questionnaire in rural Victoria.
AB  - INTRODUCTION: Rural communities continue to experience significant challenges
      recruiting and retaining physicians. The Community Apgar Questionnaire (CAQ) was
      developed in Idaho in the USA to comprehensively assess the characteristics
      associated with successful recruitment and retention of rural physicians. The CAQ
      has been utilised and validated across the USA; however, its value in rural
      Australia has not been examined. The objective of this study was to use the CAQ
      in rural Australia to examine its utility and develop a greater understanding of
      the community factors that impact general practitioner (GP) recruitment and
      retention. METHOD: The project conducted structured face-to-face interviews with
      hospital chief executive officers (CEOs) and directors of clinical services
      (DCSs) from 14 of the 21 (76%) health services that agreed to participate in
      rural north-eastern Victoria, Australia. The interviews were undertaken to
      complete the CAQ, which contains 50 questions centred on factors that influence
      physician recruitment and retention. Once completed, CAQs were scored by
      assigning quantitative values to a community's strengths and challenges including
      the level of importance placed on each factor. As such, the most important
      factors in physician recruitment, whether they are advantages or challenges for
      that community, were then weighed for their relative importance. Scores were then
      combined to create a CAQ score. To ensure reliability and validity of the
      results, three additional CAQs were purposefully administered to key general
      practices within the region. RESULTS: The 14 rural communities exhibited
      cumulative CAQ scores ranging from a high of 387 to a low score of 61. This
      suggests the tool was sensitive enough to differentiate between communities that
      were high and low performers in terms of physician recruitment. The groups of
      factors that had the greatest impact on recruitment and retention were ranked
      highest to lowest and included medical support, hospital/community support,
      economic, scope of practice and geographic factors. Overall, the highest
      individual factors to impact recruitment and retention were perception of
      quality, hospital leadership, nursing workforce and transfer arrangements.
      Conversely, the lowest factors and challenges to recruitment and retention were
      family related, specifically spousal satisfaction and access to schools.
      CONCLUSIONS: Hume, in rural Victoria, was the first international site to
      implement the CAQ to differentially diagnose a community's relative strengths and
      challenges in recruiting and retaining GPs, while supporting health facilities to
      prioritise achievable goals to improve long-term retention strategies. It
      provided each community with a tailored gap analysis, while confidentially
      sharing best practices of other health facilities. Within Hume, open
      communication and trust between GPs and health facility leadership and nursing
      staff ensures that GPs can feel valued and supported. Possible solutions for GP
      recruitment and retention must consider the social, employment and educational
      opportunities that are available for spouses and children. Participation in the
      program was useful as it helped health facilities ascertain how they were
      performing while highlighting areas for improvement.

PMID- 27884057
TI  - Patient perceptions of a Virtual Health Room installation in rural Sweden.
AB  - INTRODUCTION: The Virtual Health Room (VHR) is an ehealth initiative in the
      village of Slussfors in northern Sweden. Construction of VHRs in other locations
      is taking place, and the Centre for Rural Medicine in the Vasterbotten County
      Council primary care department has implemented a VHR evaluation framework. This
      research focuses on evaluation of patient perceptions of the usability of the VHR
      and its contribution to their health care. METHODS: Nineteen of the 25 unique
      users of the VHR during 2014/15 completed a survey asking about their attitudes
      to their own health (using the 13-question version of the Patient Activation
      Measure (PAM)), their demographic attributes, and their satisfaction with their
      visit to the VHR. RESULTS: Respondents with lower PAM scores were less satisfied
      with the technical performance of the VHR, but equally likely to think the VHR
      made a good contribution to access to health care. In contrast, older patients
      were less likely to value the contribution of the VHR, but no less likely to be
      satisfied with its technical performance. There were no relationships between
      level of education and distance travelled and perceptions of the VHR.
      CONCLUSIONS: The research clearly demonstrated the distinction between technical
      performance of an ehealth initiative and its overall contribution to health care
      and access. Evaluation frameworks need to consider both aspects of performance.
      Transferability of these findings to other settings may depend at least in part
      on the nature of the catchment area for the VHR, with the Slussfors catchment
      being quite small and the impact of distance on access consequently limited.

PMID- 27884058
TI  - Efficiency of silencing RNA for removal of transthyretin V30M in a TTR
      leptomeningeal animal model.
AB  - Some TTR mutants target the central nervous system (CNS). Familial amyloid
      polyneuropathy (FAP) with leptomeningeal involvement has been described in 9% of
      transthyretin (TTR) mutations and in valine for methionine at position 30 (V30M)
      patients. These individuals present dementia, ataxia, brain hemorrhages and focal
      neurological episodes (FNEs). FNEs occurred also in V30M FAP patients with longer
      disease duration, who have undergone liver transplant to remove the source of
      plasma mutant TTR as a form of treatment. It is thus to expect that as better
      treatments for FAP emerge and prolong survival, meningeal-vascular CNS deposition
      will increase and need special therapies. Recently, we detected TTR meningeal
      vascular deposition in a V30M TTR transgenic mouse model, opening new avenues of
      research to investigate selective treatments of this condition. Since pre
      clinical studies with TTR siRNA therapeutics were shown to promote clearance of
      TTR non-fibrillar deposits in several organs and tissues, we investigated its
      effect on TTR meningeal-vascular deposition. We show that systemically
      administered TTR siRNA promoted TTR clearance in the extracellular matrix of
      meninges and brain blood vessels. Surprisingly, despite the striking decline of
      blood TTR, cerebrospinal fluid TTR levels were unaffected. Though this is
      reassuring because siRNA will not interfere with the neuroprotective role of TTR
      in the CNS, it raises new questions on therapeutical approaches for CNS ATTR.

PMID- 27884059
TI  - DNA methylation analysis in rat kidney epithelial cells exposed to 3-MCPD and
      glycidol.
AB  - 3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant
      that has been regarded as a rat carcinogen, which is known to induce Leydig-cell
      and mammary gland tumors in males, as well as kidney tumors in both genders. 3
      MCPD is highly suspected to be a non-genotoxic carcinogen. 2,3-Epoxy-1-propanol
      (glycidol) can be formed via dehalogenation from 3-MCPD. We aimed to investigate
      the cytotoxic effects of 3-MCPD and glycidol, then to demonstrate the possible
      epigenetic mechanisms with global and gene-specific DNA methylation in rat kidney
      epithelial cells (NRK-52E). IC50 value of 3-MCPD was determined as 48 mM and
      41.39 mM, whereas IC50 value of glycidol was 1.67 mM and 1.13 mM by MTT and NRU
      test, respectively. Decreased global DNA methylation at the concentrations of 100
      MUM and 1000 MUM for 3-MCPD and 100 MUM and 500 MUM for glycidol were observed
      after 48 h exposure by using 5-methylcytosine (5-mC) ELISA kit. Methylation
      changes were detected in promoter regions of c-myc and Rassf1a in 3-MCPD and
      glycidol treated NRK-52E cells by using methylation-specific PCR (MSP), whereas
      changes on gene expression of c-myc and Rassf1a were observed by using real-time
      PCR. However, e-cadherin, p16, VHL and p15 genes were unmethylated in their CpG
      promoter regions in response to treatment with 3-MCPD and glycidol. Alterations
      in DNA methylation might be key events in the toxicity of 3-MCPD and glycidol.

PMID- 27884060
TI  - Is minimal residual disease a convincing tool to determine the treatment duration
      of immune checkpoint inhibitors?

PMID- 27884062
TI  - Corrigendum.

PMID- 27884061
TI  - Embryos cultured in a time-lapse system result in superior treatment outcomes: a
      strict matched pair analysis.
AB  - A retrospective strict matched-pair analysis of 728 treatment cycles between
      January 2011 and September 2014 was performed. A total of 364 treatment cycles,
      where all embryos were cultured and examined in EmbryoScope(r), were matched to
      treatment cycles where all the embryos were cultured in a standard incubator with
      conventional morphological examination. Matching was performed for patient age,
      number of oocytes collected, treatment type and date of oocyte collection (+/-
      six months). The clinical (CPR), implantation (IR), live birth (LBR) and
      miscarriage rates (MR) were calculated and considered significant when p < 0.05
      (Chi-square test). CPR, IR and LBR were found to be significantly higher in the
      time-lapse system (TLS) group compared to the standard incubation group (CPR =
      44.8% versus 36.5%, p = 0.02; IR = 39.3% versus 32.2%, p = 0.03; and LBR = 43.1%
      versus 33.8%, p = 0.01). Although there was a 5.5% decrease in the MR for the TLS
      group when compared to the standard incubation group, this result was not
      statistically significant (18.9% versus 24.4%, p = 0.19). There is a paucity of
      well-designed studies to confirm that embryos cultured and examined in TLS can
      result in superior treatment outcomes, and this strict-matched pair analysis with
      a large cohort of treatment cycles indicates the advantage of using TLS.

PMID- 27884063
TI  - Erratum.

PMID- 27884064
TI  - Amyloid fibril proteins and amyloidosis: chemical identification and clinical
      classification International Society of Amyloidosis 2016 Nomenclature Guidelines.
AB  - The Nomenclature Committee of the International Society of Amyloidosis (ISA) met
      during the XVth Symposium of the Society, 3 July-7 July 2016, Uppsala, Sweden, to
      assess and formulate recommendations for nomenclature for amyloid fibril proteins
      and the clinical classification of the amyloidoses. An amyloid fibril must
      exhibit affinity for Congo red and with green, yellow or orange birefringence
      when the Congo red-stained deposits are viewed with polarized light. While
      congophilia and birefringence remain the gold standard for demonstration of
      amyloid deposits, new staining and imaging techniques are proving useful. To be
      included in the nomenclature list, in addition to congophilia and birefringence,
      the chemical identity of the protein must be unambiguously characterized by
      protein sequence analysis when possible. In general, it is insufficient to
      identify a mutation in the gene of a candidate amyloid protein without confirming
      the variant changes in the amyloid fibril protein. Each distinct form of
      amyloidosis is uniquely characterized by the chemical identity of the amyloid
      fibril protein that deposits in the extracellular spaces of tissues and organs
      and gives rise to the disease syndrome. The fibril proteins are designated as
      protein A followed by a suffix that is an abbreviation of the parent or precursor
      protein name. To date, there are 36 known extracellular fibril proteins in
      humans, 2 of which are iatrogenic in nature and 9 of which have also been
      identified in animals. Two newly recognized fibril proteins, AApoCII derived from
      apolipoprotein CII and AApoCIII derived from apolipoprotein CIII, have been
      added. AApoCII amyloidosis and AApoCIII amyloidosis are hereditary systemic
      amyloidoses. Intracellular protein inclusions displaying some of the properties
      of amyloid, "intracellular amyloid" have been reported. Two proteins which were
      previously characterized as intracellular inclusions, tau and alpha-synuclein,
      are now recognized to form extracellular deposits upon cell death and thus have
      been included in Table 1 as ATau and AalphaSyn.

PMID- 27884065
TI  - The efficacy of two formulations of botulinum toxin type A for masseter
      reduction: a split-face comparison study.
AB  - BACKGROUND: Botulinum toxin type A (BTA) is now extensively used to address
      cosmetic concerns. OnabotulinumtoxinA (ONA, Botox; Allergan Inc., Irvine, CA)
      received FDA approval for upper face rejuvenation, including glabella frown lines
      and crow's-feet lines. The other off-label uses for lower face conditions have
      been utilized for contouring purposes, especially masseter hypertrophy. Recently,
      a new Daewoong BTA, (NABOTA(r), NBT, Daewoong Pharmaceutical, Seoul, Korea), was
      recently introduced. OBJECTIVE: To compare efficacy and safety of ONA and NBT for
      masseter reduction. METHODS: Thirty-five subjects with masseter hypertrophy were
      randomly injected with 25 units of ONA on one side and 25 units of NBT on the
      other side into masseter. Standardized photographic documentation was obtained at
      baseline, 1, 3 and 6 months after treatment. The mean volume of masseter was
      acquired by using three-dimensional computed tomography (3-D CT) at baseline, 3-,
      and 6-month follow-up visits. In addition, patients' satisfaction and side
      effects were also record at every follow-up visits. RESULTS: The mean masseter
      volume on the sides treated with ONA and NBT at baseline were 21.20 +/- 4.23 cm3
      and 21.26 +/- 4.58 cm3, respectively. There was no statistically significant
      difference in the mean volume of both sides (p= 0.827). The mean masseter volume
      at 3- and 6-month follow-up visits reduced significantly on both ONA and NBT
      sides (p< 0.001 and p< 0.001, respectively). However, there was no statistically
      significant difference in mean masseter volume when comparing between ONA and NBT
      sides at 3 and 6 months after treatment (p= 0.769 and p = 0.346, respectively).
      There was also no statistically significant difference in masseter reduction when
      compared between ONA and NBT sides evaluated by physicians and patients at each
      follow-up visit. No side effect on both sides was reported after injection.
      CONCLUSIONS: This study demonstrated that ONA and NBT provided comparable
      efficacy and safety for masseter reduction.

PMID- 27884066
TI  - Training a model for estimating leukocyte composition using whole-blood DNA
      methylation and cell counts as reference.
AB  - AIM: Whole-blood DNA methylation depends on the underlying leukocyte composition
      and confounding hereby is a major concern in epigenome-wide association studies.
      Cell counts are often missing or may not be feasible. Computational approaches
      estimate leukocyte composition from DNA methylation based on reference datasets
      of purified leukocytes. We explored the possibility to train such a model on
      whole-blood DNA methylation and cell counts without the need for purification.
      MATERIALS & METHODS: Using whole-blood DNA methylation and corresponding five
      part cell counts from 2445 participants from the London Life Sciences Prospective
      Population Study, a model was trained on a subset of 175 subjects and evaluated
      on the remaining. RESULTS: Correlations between cell counts and estimated cell
      proportions were high (neutrophils 0.85, eosinophils 0.88, basophils 0.02,
      lymphocytes 0.84, monocytes 0.55) and estimated proportions explained more
      variance in whole-blood DNA methylation levels than counts. CONCLUSION: Our model
      provided precise estimates for the common cell types.

PMID- 27884067
TI  - Psychosocial correlates of safe sex communication between Latina women and their
      stable male partners: an integrative review.
AB  - Latina women in stable relationships have risks for human immunodeficiency virus
      and other sexually transmitted infections. Improving safe sexual communication
      (SSC) could enable women to accurately assess and mitigate their risk of
      infection within their relationship. Literature to identify psychosocial
      correlates that facilitate or inhibit SSC between Latina women and their partners
      has not yet been synthesized. The purpose of this study was to conduct an
      integrative review and synthesis of empirical and theoretical research that
      examines psychosocial correlates of SSC among adult Latina women from the United
      States, Latina America, and the Caribbean with stable male partners. A systematic
      search of LILACS, EBSCO, and PsychInfo databases was conducted to identify
      qualitative and quantitative studies that investigated psychosocial correlates of
      SSC among adult Latina women with a stable male partner. Pertinent data were
      abstracted and quality of individual studies was appraised. A qualitative
      synthesis was conducted following Miles and Huberman's method. Five qualitative
      and three quantitative studies meet eligibility criteria. Factors related to SSC
      related to three main themes: (1) relationship factors such as length, quality,
      and power/control, (2) individual factors including attitudes, beliefs,
      background, behaviors, and intrapersonal characteristics, and (3) partner factors
      related to partner beliefs and behaviors. The interplay of relationship,
      individual, and partner factors should be considered in the assessment of SSC for
      Latina women with their stable partners. To inform future interventions and
      clinical guidelines, additional research is needed to identify which factors are
      most related to SSC for this population, and how comparable experiences are for
      Latina women of different subcultures and living in different countries.

PMID- 27884069
TI  - Risk factors of incomplete Apgar score and umbilical cord blood gas analysis: a
      retrospective observational study.
AB  - OBJECTIVE: To investigate whether incomplete umbilical cord blood gas (UCBG)
      analysis occurs more often than the incomplete reporting of the Apgar score, and
      risk factors associated with the incomplete values. METHODS: A total of 8824
      infants born alive after 26 weeks' gestation between January 2009 and April 2013
      were included. We extracted data on five-minute Apgar score, UCBG analysis,
      gestational age, mode of delivery, time of delivery and multiple pregnancy.
      Univariate and multivariable logistic regression analyses were performed.
      RESULTS: Five-minute Apgar score was incomplete in 15 cases (0.2%) and UCBG
      analysis in 1960 cases (22.2%), p < 0.05. Incomplete UCBG analysis was
      significantly more likely to occur in situations with Apgar score below seven
      (Odds ratio (OR) 1.68, 95% CI;1.29-2.19), gestational age between 26 to 27 6/7
      and 28 to 31 6/7 weeks (OR 3.14, 95% CI; 2.13-4.62 and OR 1.91, 95% CI; 1.57
      2.32), cesarean section (OR 1.31, 95% CI; 1.11-1.55), and multiple pregnancy (OR
      2.02, 95% CI; 1.69-2.43). Deliveries during night time had a lower risk of
      incomplete UCBG analysis (OR 0.78, 95% CI; 0.69-0.88). CONCLUSIONS: Measuring
      five-minute Apgar score generated less incomplete data compared with UCBG
      analysis. The risk factors associated with incomplete UCBG analysis were noted.
      Study outcomes with UCBG analysis as neonatal assessment tool should be
      interpreted with caution.

PMID- 27884068
TI  - Silver nanoparticle exposure in pregnant rats increases gene expression of
      tyrosine hydroxylase and monoamine oxidase in offspring brain.
AB  - CONTEXT: Maternal exposure to silver nanoparticles (AgNPs) affects
      neurobehavioral reflexes and spatial memory formation in offspring. Although the
      transmission of AgNPs into the brain has been reported, its toxic effect on
      dopamine metabolism in the brain of offspring has not been studied so far.
      OBJECTIVE: The aim of the present study was to investigate the expression levels
      of tyrosine hydroxylase (TH) and monoamine oxidase A (MAO-A) genes in the brain
      of offspring exposed in utero to various concentrations of AgNPs. MATERIALS AND
      METHODS: Time mated pregnant adult rats were assigned into three groups including
      control, low dose of AgNPs (0.2 mg/kg) and high dose of AgNPs (2 mg/kg). AgNPs
      were subcutaneously (SC) injected at days of 1, 4, 7, 10, 13, 16 and 19 of
      pregnancy. Gene expression of TH and MAO-A was analyzed in the brain of offspring
      (male and female) at days of 1, 7, 14 and 21 after birth. RESULTS: Administration
      of AgNPs to pregnant rats in a time- and dose-dependent manner increased the
      expression levels of TH in the brain of male and female pups at all tested days
      after birth (p < 0.05). AgNPs had stimulatory effect on MAO-A mRNA expression in
      pups only at the age of 7 and 14. Female pups showed the higher level of TH and
      MAO-A compared to that in male pups (p < 0.001). DISCUSSION AND CONCLUSIONS:
      Results obtained here demonstrated that the exposure of pregnant rats to AgNPs
      increases the expression of genes involved in dopamine metabolism in the brain of
      offspring.

PMID- 27884070
TI  - Association of SP-C gene codon 186 polymorphism (rs1124) and risk of RDS.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) is a severe pulmonary disease
      that mainly affects preterm neonates. Surfactant-protein genes' polymorphisms
      have been mostly evaluated as the candidate contributors in genetics of RDS.
      However, the results are diverse in different populations. We aimed at
      investigating the association of rs1124 with RDS development. METHOD: Three
      hundred and thirty five preterm neonates were enrolled in a multicenter case
      control study. Respiratory distress (RD) was scored according to Downes' scoring
      system. Genotyping was performed by PCR-RFLP method. RESULT: One hundred and
      sixty six neonates showed RDS and 169 did not. Gestational age (GA) was
      significantly lower in RDS group compared to the controls. In female preterm
      newborns, AA genotype was found more frequently in RDS group. In RDS group, AA
      genotype was also associated with milder RD irrespective of gender. In neonates
      who were born 28-34 weeks, RD appeared to be more severe in the RDS group and
      males. CONCLUSIONS: This is the first report of association of SFTPC rs1124
      polymorphism with RDS development in Iranian newborns. The current study suggests
      that GA <28-weeks is the most important factor in predisposition to RDS. AA
      genotype is also, a predisposing factor for the development of RDS in female
      preterm infants.

PMID- 27884071
TI  - A pilot study on the motivational effects of an internet-delivered physical
      activity behaviour change programme in Nova Scotian cancer survivors.
AB  - OBJECTIVE: To examine the effects of an internet-delivered, distance-based
      physical activity (PA) behaviour change programme on motivation to perform PA in
      cancer survivors. DESIGN: Breast, prostate and colorectal cancer survivors (N =
      95) were randomized to either an online Theory of Planned Behaviour (TPB)-based
      PA behaviour change programme (UCAN) or usual care. MAIN OUTCOME MEASURES:
      Motivational variables from the TPB including intention, planning, attitude,
      subjective norm, perceived behavioural control and underlying beliefs. RESULTS:
      UCAN had significant negative effects on self-efficacy (-.7; 95% CI = -1.2 to 
      .1; d = -.53, p = .019), affective attitude (-.4; 95% CI = -.8 to -.0; d = -.45,
      p = .044), instrumental attitude (-.5; 95% CI = -.9 to -.1; d = -.43, p = .026)
      and confidence to perform PA in bad weather (-.8; 95% CI = -1.6 to -.1; d = -.49,
      p = .030), despite health issues (-.7; 95% CI = -1.3 to -.1; d = -.48, p = .031),
      despite pain/soreness (-.7; 95% CI = -1.4 to -.1; d = -.52, p = .020), despite
      family responsibilities (-1.0; 95% CI = -1.7 to -.3; d = -.62, p = .005) and when
      PA is boring (-.8; 95% CI = -1.4 to -.1; d = -.54, p = .016). CONCLUSION: UCAN
      had negative effects on motivational variables in cancer survivors. These
      findings may be explained by methodological issues related to measuring
      motivation and/or the absence of post-intentional constructs.

PMID- 27884072
TI  - The biological effect of asbestos exposure is dependent on changes in iron
      homeostasis.
AB  - Functional groups on the surface of fibrous silicates can complex iron. We tested
      the postulate that (1) asbestos complexes and sequesters host cell iron resulting
      in a disruption of metal homeostasis and (2) this loss of essential metal results
      in an oxidative stress and biological effect in respiratory epithelial cells.
      Exposure of BEAS-2B cells to 50 MUg/mL chrysotile resulted in diminished
      concentrations of mitochondrial iron. Preincubation of these cells with 200 MUM
      ferric ammonium citrate (FAC) prevented significant mitochondrial iron loss
      following the same exposure. The host response to chrysotile included increased
      expression of the importer divalent metal transporter-1 (DMT1) supporting a
      functional iron deficiency. Incubation of BEAS-2B cells with both 200 MUM FAC and
      50 MUg/mL chrysotile was associated with a greater cell accumulation of iron
      relative to either iron or chrysotile alone reflecting increased import to
      correct metal deficiency immediately following fiber exposure. Cellular oxidant
      generation was elevated after chrysotile exposure and this signal was diminished
      by co-incubation with 200 MUM FAC. Similarly, exposure of BEAS-2B cells to 50
      MUg/mL chrysotile was associated with release of the proinflammatory mediators
      interleukin (IL)-6 and IL-8, and these changes were diminished by co-incubation
      with 200 MUM FAC. We conclude that (1) the biological response following exposure
      to chrysotile is associated with complexation and sequestration of cell iron and
      (2) increasing available iron in the cell diminished the effects of asbestos
      exposure.

PMID- 27884073
TI  - Liquid chromatography-high-resolution mass spectrometry for regulated
      bioanalysis: bile acid and oligonucleotide quantitation as a reference.

PMID- 27884076
TI  - Corrigenda.

PMID- 27884075
TI  - SRM-based measurements of proprotein convertase subtilisin/kexin type 9 and
      lipoprotein(a) kinetics in nonhuman primate serum.
AB  - AIM: PCSK9 and Lp(a) have been identified as potential biomarkers for
      cardiovascular disease. The ability to measure protein turnover rates will
      provide insights into the dynamic properties of these proteins and lead to better
      understanding of their biological roles. We aimed to implement the stable isotope
      labeled tracers ([2H3]-leucine) and develop a novel LC-selected reaction
      monitoring (SRM) mass spectrometry (MS) method to study the kinetics of PCSK9 and
      Lp(a). RESULTS: A sensitive method using immunoaffinity enrichment coupled with
      LC-SRM MS was developed to measure the production and degradation rates of PCSK9
      and Lp(a) in naive nonhuman primate serum. Comparable results were obtained from
      two different routes of tracer administration. CONCLUSION: Immunoaffinity
      enrichment coupled with LC-SRM MS demonstrated success in in vivo kinetic
      measurements of proteins with relatively slow turnover rate (Lp[a]) or low
      abundance (PCSK9) in serum.

PMID- 27884077
TI  - From patient to tube: the importance of physiologically relevant quantitative
      bioanalytical assays.
AB  - Circulating drug concentrations (clinical or preclinical) underly many
      interactions between industry and regulators; expressing safety coverage,
      pharmacokinetic-pharmacodynamic relationships or defining bioequivalence and
      dosing regimens. Accurate and precise measurement of these circulating
      concentrations is pivotal to the evolution and validation of any bioanalytical
      method that supports regulatory interactions. Since the bioanalyst is presented
      with a sub-aliquot of sampled biological matrix, how do they ensure this aliquot
      reflects the concentration in the subject at the time of collection? Here we
      share experiences from project support (internal and at CROs) that suggests we
      need to be ever vigilant translating the needs of bioanalysis with those of
      project teams. The simple mantra is for bioanalytical measurements to be
      physiologically relevant to the patient.

PMID- 27884074
TI  - LC-MS/MS strategies for therapeutic antibodies and investigation into the
      quantitative impact of antidrug-antibodies.
AB  - AIM: We aimed to establish novel, high-throughput LC-MS/MS strategies for
      quantification of monoclonal antibodies in human serum and examine the potential
      impact of antidrug antibodies. METHODOLOGY: We present two strategies using a
      thermally stable immobilized trypsin. The first strategy uses whole serum
      digestion and the second introduces Protein G enrichment to improve the
      selectivity. The impact of anti-trastuzumab antibodies on the methods was tested.
      CONCLUSION: Whole serum digestion has been validated for trastuzumab (LLOQ 0.25
      ug/ml). Protein G enrichment has been validated for trastuzumab (LLOQ 0.1 ug/ml),
      bevacizumab (LLOQ 0.1 ug/ml) and adalimumab (LLOQ 0.25 ug/ml). We have shown the
      potential for anti-drug antibodies to impact on the quantification and we have
      subsequently established a strategy to overcome this impact where total
      quantification is desired.

PMID- 27884078
TI  - A semi-universal assay platform to quantitate vaccines with potential
      applications for biotherapeutics.
AB  - AIM: Biologics development often requires multiple immunoassays to evaluate both
      assay reagents and potential drug candidates resulting in extensive analytical
      development. METHODOLOGY: We developed a semi-universal, 5-layer platform assay
      on Gyrolab using secondary antispecies or anti-isotype-specific capture and
      detection antibodies. We applied the assay to several multivalent vaccines.
      RESULTS: Method performance exhibited a median accuracy of 110%, reproducibility
      of 9% CV and intermediate precision of 11% CV. System suitability criteria were
      met for 92.5% of the samples and only one out of 31 replicate samples exhibited a
      %CV greater than 20%. CONCLUSION: The semi-universal Gyrolab assay allowed assay
      development without reagent labeling. The format could also be translated into a
      plate-based assay.

PMID- 27884080
TI  - Decomposition products of glycidyl esters of fatty acids by heating.
AB  - In this study, decomposition products of glycidyl palmitate (GP) of fatty acids
      heated at high temperature such as deep frying were investigated. When GP and
      tripalmitin (TP) were heated at 180 and 200  degrees C, they were decreased with
      heating time. The weight of GP was less than that of TP, although both GP and TP
      were converted to polar compounds after heating. The decomposition rate of GP was
      higher than TP. Both GP and TP produced considerable amounts of hydrocarbons and
      aldehydes during heating. Aldehydes produced from GP and TP included saturated
      aldehydes with carbon chain length of 3-10, while hydrocarbons consisted of
      carbon chain length of 8-15. It was observed that major hydrocarbons produced
      from GP during heating were pentadecane. Moreover, the level of carbon dioxide
      (CO2) released from GP was higher than that of TP. It was suggested that fatty
      acids in GE might be susceptible to decarboxylation. From these results, GP might
      be quickly decomposed to hydrocarbons, aldehydes and CO2 besides polar compounds
      by heating, in comparison with TP.

PMID- 27884079
TI  - Bypassing nonparallelism of a monoclonal antibody ligand-binding assay by
      employment of alternative assay formats.
AB  - Determination of concentration-time profiles in cynomolgus monkeys of a
      therapeutic monoclonal antibody against a soluble target revealed a substantial
      discrepancy between a generic anti-human IgG capture/detection and target
      bridging assay with the target bridging assay leading to dose- and time-dependent
      underquantification of drug concentrations, lack of parallelism and subsequently
      different pharmacokinetic parameters. In contrast, plasma levels derived from a
      target capture and an anti-idiotypic antibody bridging assay were in close
      concordance with the generic assay and demonstrated parallelism with high
      precision across several dilutions. The results provide a practical attempt to
      overcome nonparallelism by employing alternative assay formats utilizing tailored
      assay reagent combinations in order to obtain unbiased pharmacokinetic data.

PMID- 27884081
TI  - A randomized cross over study comparing the efficacy of two mandibular
      advancement appliances in the treatment of mild-moderate obstructive sleep apnea.
AB  - OBJECTIVE: To compare efficacy, side effects, patient compliance, and preference
      between two types of custom-made mandibular advancement appliances (MAAs) in the
      treatment of patients with mild to moderate obstructive sleep apnea (OSA).
      METHODOLOGY: This prospective, randomized, crossover study of 12 patients with
      mild to moderate OSA compared a titratable and a non-titratable MAA. Each patient
      was fitted with both appliances in a random order with a washout period of two
      weeks. Efficacy, side effects, compliance, and preference were evaluated by a
      questionnaire. All patients underwent overnight home sleep recordings prior to
      and after the use of each appliance in order to objectively assess sleep quality
      in terms of the apnea and hypopnea index (AHI), snoring frequency and oxygen
      desaturation index. RESULTS: Treatment successes (relief of symptoms and/or
      reduction of AHI to <10/h) were reported with both types of appliances. No
      compliance failure was reported, and in most patients, the side effects were
      mild, and improved with time. CONCLUSION: Both types of oral appliances were
      effective treatments for patients with mild to moderate OSA, with fewer side
      effects and higher patient satisfaction.

PMID- 27884082
TI  - Enhanced conformational flexibility of the histone-like (HU) protein from
      Mycoplasma gallisepticum.
AB  - The histone-like (HU) protein is one of the major nucleoid-associated proteins
      involved in DNA supercoiling and compaction into bacterial nucleoid as well as in
      all DNA-dependent transactions. This small positively charged dimeric protein
      binds DNA in a non-sequence specific manner promoting DNA super-structures. The
      majority of HU proteins are highly conserved among bacteria; however, HU protein
      from Mycoplasma gallisepticum (HUMgal) has multiple amino acid substitutions in
      the most conserved regions, which are believed to contribute to its specificity
      to DNA targets unusual for canonical HU proteins. In this work, we studied the
      structural dynamic properties of the HUMgal dimer by NMR spectroscopy and MD
      simulations. The obtained all-atom model displays compliance with the NMR data
      and confirms the heterogeneous backbone flexibility of HUMgal. We found that
      HUMgal, being folded into a dimeric conformation typical for HU proteins, has a
      labile alpha-helical body with protruded beta-stranded arms forming DNA-binding
      domain that are highly flexible in the absence of DNA. The amino acid
      substitutions in conserved regions of the protein are likely to affect the
      conformational lability of the HUMgal dimer that can be responsible for complex
      functional behavior of HUMgal in vivo, e.g. facilitating its spatial adaptation
      to non-canonical DNA-targets.

PMID- 27884084
TI  - Losartan loaded liposomes improve the antitumor efficacy of liposomal paclitaxel
      modified with pH sensitive peptides by inhibition of collagen in breast cancer.
AB  - The dense collagen network in tumors restricts the penetration of drugs into
      tumors. Free losartan could inhibit collagen, but it would cause hypotension at
      the dosage of 10 mg/kg/d. In this study, losartan was encapsulated in liposomes
      (LST-Lip) and the collagen inhibition ability of LST-Lip was investigated. Our
      results showed the blood pressure was not affected by LST-Lip at the dosage of
      2.5 mg/kg every other day. The amount of Evans Blue in tumor in LST-Lip group was
      1.98 times of that in control group. Confocal laser scanning microscopy images
      showed that prior injection of LST-Lip could inhibit collagen and further improve
      the tumorous accumulation of liposomes modified with TH peptides
      (AGYLLGHINLHHLAHL(Aib)HHIL-NH2) (TH-Lip) in 4T1 tumors. Compared with control
      group, the tumor inhibition rate of combined strategy of LST-Lip and paclitaxel
      loaded TH-Lip (PTX-TH-Lip) was 41.73%, while that of group only treated with PTX
      TH-Lip was 14.94%. Masson's trichrome staining confirmed that collagen was
      inhibited in LST-Lip group. Thus, the administration of LST-Lip in advance could
      inhibit the collagen in tumors effectively and did not affect the blood pressure,
      then PTX-TH-Lip injected subsequently could exert enhanced antitumor efficacy. In
      conclusion, this combined strategy might be promising for breast cancer therapy.

PMID- 27884085
TI  - The roles of myeloperoxidase in coronary artery disease and its potential
      implication in plaque rupture.
AB  - Atherosclerosis is the main pathophysiological process underlying coronary artery
      disease (CAD). Acute complications of atherosclerosis, such as myocardial
      infarction, are caused by the rupture of vulnerable atherosclerotic plaques,
      which are characterized by thin, highly inflamed, and collagen-poor fibrous caps.
      Several lines of evidence mechanistically link the heme peroxidase
      myeloperoxidase (MPO), inflammation as well as acute and chronic manifestations
      of atherosclerosis. MPO and MPO-derived oxidants have been shown to contribute to
      the formation of foam cells, endothelial dysfunction and apoptosis, the
      activation of latent matrix metalloproteinases, and the expression of tissue
      factor that can promote the development of vulnerable plaque. As such, detection,
      quantification and imaging of MPO mass and activity have become useful in cardiac
      risk stratification, both for disease assessment and in the identification of
      patients at risk of plaque rupture. This review summarizes the current knowledge
      about the role of MPO in CAD with a focus on its possible roles in plaque rupture
      and recent advances to quantify and image MPO in plasma and atherosclerotic
      plaques.

PMID- 27884083
TI  - The globalisation strategies of five Asian tobacco companies: An analytical
      framework.
AB  - With 30% of the world's smokers, two million deaths annually from tobacco use,
      and rising levels of tobacco consumption, the Asian region is recognised as
      central to the future of global tobacco control. There is less understanding,
      however, of how Asian tobacco companies with regional and global aspirations are
      contributing to the global burden of tobacco-related disease and death. This
      introductory article sets out the background and rationale for this special issue
      on 'The Emergence of Asian Tobacco Companies: Implications for Global Health
      Governance'. The article discusses the core questions to be addressed and
      presents an analytical framework for assessing the globalisation strategies of
      Asian tobacco firms. The article also discusses the selection of the five case
      studies, namely as independent companies in Asia which have demonstrated
      concerted ambitions to be a major player in the world market.

PMID- 27884086
TI  - Predictors of satisfaction in patient with silicone breast implants and its
      association with drug intake habits.
AB  - BACKGROUND: Satisfaction is an important outcome variable in surgical success.
      The purpose of this study is to evaluate predictors of satisfaction in women
      submitted to silicone textured breast implant surgery. METHODS: A retrospective
      evaluation of women receiving textured silicone breast implants was performed.
      Patients were divided in four groups: cosmetic cohort (n = 104), reconstructive
      cohort (n = 120), general population control cohort (n = 120) and aesthetic
      control cohort (n = 54). Data were collected based on information retrieved from
      patient records, a planned consultation and a self-administered structured
      questionnaire. RESULTS: Patient satisfaction was influenced by preoperative
      information (p = .007), cohort (p < .001), and occurrence of postoperative
      complications (p < .001). The degree of satisfaction was also related with drug
      intake habits: women using psychotropic drugs were 3-fold more likely to report
      poor satisfaction than those that never used these drugs (p < .001). CONCLUSION:
      The purpose of the surgery, preoperative information and the occurrence of
      postoperative complications have an impact on the degree of satisfaction of women
      submitted to silicone breast implant surgery. Women using psychotropic drugs are
      more likely to report poor satisfaction.

PMID- 27884088
TI  - Physiopathology, clinical diagnosis, and treatment of hyponatremia.
AB  - Hyponatremia is the commonest electrolyte disorder encountered in clinical
      practice. It develops when the mechanisms regulating water and electrolyte
      handling are impaired, which in many instances occur in the setting of concurrent
      diseases such as heart failure, liver failure, renal failure etc... Hyponatremia
      as an electrolyte disorder has several specificities: when profound it can be
      quickly fatal and when moderate it carries a high risk of mortality and
      morbidity, but at the same time incorrect treatment of profound hyponatremia can
      lead to debilitating neurological disease and it remains unclear if treatment of
      moderate hyponatremia is associated with a decrease in mortality and morbidity. A
      proper diagnosis is the keystone for an adequate treatment for hyponatremia and
      in the last few years many diagnosis algorithms have been developed to aid in the
      evaluation of the hyponatremic patient. Also because of the availability of
      vasopressin receptor antagonists and the advances made in the research regarding
      complications associated with hyponatremia treatment, new treatment
      recommendations have been published recently by several panels. This review will
      discuss the physiopathology, epidemiology, and clinical manifestations of
      hyponatremia and also the diagnosis and the treatment of this disorder with
      special emphasis on the complication from overly rapid correction of
      hyponatremia.

PMID- 27884087
TI  - A protease/peptidase from culture medium of Flammulina velutipes that acts on
      arabinogalactan-protein.
AB  - Arabinogalactan-proteins (AGPs) are highly diverse plant proteoglycans found on
      the plant cell surface. AGPs have large arabinogalactan (AG) moieties attached to
      a core-protein rich in hydroxyproline (Hyp). The AG undergoes hydrolysis by
      various glycoside hydrolases, most of which have been identified, whereas the
      core-proteins is presumably degraded by unknown proteases/peptidases secreted
      from fungi and bacteria in nature. Although several enzymes hydrolyzing other Hyp
      rich proteins are known, the enzymes acting on the core-proteins of AGPs remain
      to be identified. The present study describes the detection of protease/peptidase
      activity toward AGP core-proteins in the culture medium of winter mushroom
      (Flammulina velutipes) and partial purification of the enzyme by several
      conventional chromatography steps. The enzyme showed higher activity toward Hyp
      residues than toward proline and alanine residues and acted on core-proteins
      prepared from gum arabic. Since the activity was inhibited in the presence of
      Pefabloc SC, the enzyme is probably a serine protease.

PMID- 27884089
TI  - An animal model of effects of nicotine exposure on endometrial receptivity and
      embryo implantation in pregnancy.
AB  - OBJECTIVE: This study aims at evaluating the endometrial receptivity in uterus of
      pregnant rats exposed to nicotine via examination of integrin expression by
      immunohistochemical effect. METHODS: In this study, 16 healthy pregnant rats were
      divided into two groups of control and study groups each comprising eight rats.
      The rats randomised to study group were given a certain amount of nicotine before
      and during the pregnancy. Integrin expression was detected in uterus of all rats
      by immunohistochemical staining. The effect of nicotine exposure on embryo
      implantation and the endometrial receptivity were immunohistochemically and
      pathologically evaluated. RESULTS: Comparison of both groups revealed no
      difference in living, viable foetuses. Intensity and universality of
      immunohistochemical staining of Integrin beta3 for endometrial epithelium and
      endometrial stroma were detected to be identical between the groups. CONCLUSION:
      No immunochemical effect was observed on integrin expression, which is a very
      important part of receptivity in an animal model created with pregnant rats that
      were transdermally exposed to nicotine. Our study demonstrated that the harmful
      effect of nicotine use before and pregnancy on implantation is limited at the
      level of integrin expression, in a dose-dependent manner and also by considering
      the method of administration.

PMID- 27884090
TI  - Aloe QDM complex enhances specific cytotoxic T lymphocyte killing in vivo in
      metabolic disease mice.
AB  - We developed spontaneous diet-induced metabolic disease in mice by feeding them a
      high-fat diet for 23 weeks and administered Aloe QDM complex for 16 weeks to
      examine its restorative effect on immune disorders and metabolic syndrome. A
      series of immune functional assays indicated Aloe QDM complex enhanced lymphocyte
      proliferation and antigen-specific immunity as determined by the restored
      functions of cytotoxic T lymphocytes (CTL) and IgG production. The elevated serum
      TNF-alpha level was also regulated by Aloe QDM complex treatment, which suggested
      its complex therapeutic potential. As for metabolic phenotypes, oral
      administration of Aloe QDM complex significantly improved diabetic symptoms,
      including high fasting glucose levels and glucose tolerance, and distinctly
      alleviated lipid accumulation in adipose and hepatic tissue. The simultaneous
      restoration of Aloe QDM complex on metabolic syndrome and host immune
      dysfunction, especially on the specific CTL killing was first elucidated in our
      study.

PMID- 27884091
TI  - Whipple's disease.
AB  - In recent years, it has become apparent that Tropheryma whipplei not only causes
      a chronic multisystemic infection which is often preceded by arthropathies for
      many years, well known as 'classical' Whipple's disease, but also clinically
      becomes manifest with localized organ affections and acute (transient) infections
      in children. T. whipplei is found ubiquitously in the environment and colonizes
      in some healthy carriers. In this review, we highlight new aspects of this
      enigmatic infectious disorder.

PMID- 27884092
TI  - A retrospective analysis of outcomes for primary mediastinal large B-cell
      lymphoma treated with RCHOP followed by radiotherapy or front-line autologous
      stem cell transplantation.
AB  - OBJECTIVES: Our aim was to retrospectively investigate the data from our
      institute the response rate and outcome in patients with primary mediastinal B
      cell lymphoma (PMBL) who received the rituximab in combination with CHOP (RCHOP)
      followed by autologous stem cell transplantation (ASCT) or RCHOP followed by
      involved field radiation therapy (IFRT). METHODS: Sixty five patients with PMBL
      received RCHOP as first-line chemotherapy between January 2005 and December 2010.
      Forty of the 65 patients completed the planned subsequent IFRT after initial
      chemotherapy. Thirteen of the 65 patients received the front-line ASCT after
      RCHOP. Twelve patients received RCHOP alone. RESULTS: Thirty two of the 40
      patients who received the RCHOP followed by IFRT have complete remission (CR) or
      CRu (CR/unconfirmed). All patients have CR or CRu after the ASCT. The progression
      free survival (PFS) and the estimated overall survival (OS) rate at 5 years for
      32 CR/CRu patients in the RCHOP followed by IFRT group were 57 and 65%,
      respectively, as compared to RCHOP/ASCT group who were 94 and 100%, respectively.
      Twelve patients who received RCHOP alone had the same PFS and OS rate as the 40
      patients who received RCHOP/IFRT (5-year PFS:62 vs. 65%, p = 0.068; 5-year OS:57
      vs. 67%, p = 0.058). For all 65 patients, the age-adjusted international
      prognostic index (aaIPI) score remained the only predictor of a worse outcome.
      CONCLUSION: The PFS and OS rate of RCHOP/IFRT were found to be unsatisfied.
      RCHOP/ASCT showed a satisfactory PFS and OS rate.

PMID- 27884096
TI  - Recognizing that truth is unattainable and attending to the most informative
      research evidence.

PMID- 27884095
TI  - In pursuit of truth: A critical examination of meta-analyses of cognitive
      behavior therapy.
AB  - OBJECTIVE: Three recent meta-analyses have made the claim, albeit with some
      caveats, that cognitive-behavioral treatments (CBT) are superior to other
      psychotherapies, in general or for specific disorders (e.g., social phobia).
      METHOD: The purpose of the present article was to examine four issues in meta
      analysis that mitigate claims of CBT superiority: (a) effect size, power, and
      statistical significance, (b) focusing on disorder-specific symptom measures and
      ignoring other important indicators of psychological functioning, (c) problems
      inherent in classifying treatments provided in primary studies into classes of
      treatments, and (d) the inclusion of problematic trials, which biases the
      results, and the exclusion of trials that fail to find differences among
      treatments. RESULTS: When these issues are examined, the effects demonstrating
      the superiority of CBT are small, nonsignificant for the most part, limited to
      targeted symptoms, or are due to flawed primary studies. CONCLUSION: Meta
      analytic evidence for the superiority of CBT in the three meta-analysis are
      nonexistent or weak.

PMID- 27884093
TI  - Socio-economic status and fertility decline: Insights from historical transitions
      in Europe and North America.
AB  - The timings of historical fertility transitions in different regions are well
      understood by demographers, but much less is known regarding their specific
      features and causes. In the study reported in this paper, we used longitudinal
      micro-level data for five local populations in Europe and North America to
      analyse the relationship between socio-economic status and fertility during the
      fertility transition. Using comparable analytical models and class schemes for
      each population, we examined the changing socio-economic differences in marital
      fertility and related these to common theories on fertility behaviour. Our
      results do not provide support for the hypothesis of universally high fertility
      among the upper classes in pre-transitional society, but do support the idea that
      the upper classes acted as forerunners by reducing their fertility before other
      groups. Farmers and unskilled workers were the latest to start limiting their
      fertility. Apart from these similarities, patterns of class differences in
      fertility varied significantly between populations.

PMID- 27884094
TI  - Synthesis, characterization, and photocatalytic activity of
      sonochemical/hydration-dehydration prepared ZnO rod-like architecture
      nano/microstructures assisted by a biotemplate.
AB  - ZnO nanoparticles of rod-like architecture have excellent potential to be used in
      wastewater treatment as a photocatalyst. They were synthesized by utilizing
      sonochemical/hydration- dehydration techniques using glutamine as a biotemplate.
      The effects of calcination temperatures, that is, 300 degrees C, 500 degrees C,
      and 700 degrees C, on the crystallinity, optical properties, and photocatalytic
      activity of synthesized zinc oxide nanoparticles were investigated. X-ray
      diffraction (XRD) results indicated that all calcinated samples have a
      crystalline hexagonal wurtzite structure. Morphology and elemental compositions
      were investigated using field emission-scanning electron microscopy with energy
      dispersive X-ray spectroscopy. The XRD and Fourier transform infrared (FTIR)
      spectra revealed that the samples were amorphous at 100 degrees C; however, it
      changed into a crystalline structure amid the calcination process. Optical
      properties were determined using a UV-visible reflection spectrophotometer and
      showed abatement in the band gap with increasing annealing temperature. The
      progress of the photocatalytic degradation was monitored by a UV-visible
      spectrophotometer, while the mineralization ability was estimated by total
      organic carbon tests of ZnO-calcinated samples. The effect of various operational
      parameters the photocatalytic efficiency and rate of dye degradation was studied.
      High photocatalytic degradation of maxilon blue dye (GRL) was found at pH 6.3.

PMID- 27884097
TI  - In the pursuit of truth, we should not prioritize correlational over causal
      evidence.

PMID- 27884098
TI  - Medical Teacher in Ten Minutes.

PMID- 27884099
TI  - Medical Teacher Reviewers in 2016.

PMID- 27884101
TI  - variancePartition: interpreting drivers of variation in complex gene expression
      studies.
AB  - BACKGROUND: As large-scale studies of gene expression with multiple sources of
      biological and technical variation become widely adopted, characterizing these
      drivers of variation becomes essential to understanding disease biology and
      regulatory genetics. RESULTS: We describe a statistical and visualization
      framework, variancePartition, to prioritize drivers of variation based on a
      genome-wide summary, and identify genes that deviate from the genome-wide trend.
      Using a linear mixed model, variancePartition quantifies variation in each
      expression trait attributable to differences in disease status, sex, cell or
      tissue type, ancestry, genetic background, experimental stimulus, or technical
      variables. Analysis of four large-scale transcriptome profiling datasets
      illustrates that variancePartition recovers striking patterns of biological and
      technical variation that are reproducible across multiple datasets. CONCLUSIONS:
      Our open source software, variancePartition, enables rapid interpretation of
      complex gene expression studies as well as other high-throughput genomics assays.
      variancePartition is available from Bioconductor:
      http://bioconductor.org/packages/variancePartition .

PMID- 27884103
TI  - ampliMethProfiler: a pipeline for the analysis of CpG methylation profiles of
      targeted deep bisulfite sequenced amplicons.
AB  - BACKGROUND: CpG sites in an individual molecule may exist in a binary state
      (methylated or unmethylated) and each individual DNA molecule, containing a
      certain number of CpGs, is a combination of these states defining an
      epihaplotype. Classic quantification based approaches to study DNA methylation
      are intrinsically unable to fully represent the complexity of the underlying
      methylation substrate. Epihaplotype based approaches, on the other hand, allow
      methylation profiles of cell populations to be studied at the single molecule
      level. For such investigations, next-generation sequencing techniques can be
      used, both for quantitative and for epihaplotype analysis. Currently available
      tools for methylation analysis lack output formats that explicitly report CpG
      methylation profiles at the single molecule level and that have suited
      statistical tools for their interpretation. RESULTS: Here we present
      ampliMethProfiler, a python-based pipeline for the extraction and statistical
      epihaplotype analysis of amplicons from targeted deep bisulfite sequencing of
      multiple DNA regions. CONCLUSIONS: ampliMethProfiler tool provides an easy and
      user friendly way to extract and analyze the epihaplotype composition of reads
      from targeted bisulfite sequencing experiments. ampliMethProfiler is written in
      python language and requires a local installation of BLAST and (optionally) QIIME
      tools. It can be run on Linux and OS X platforms. The software is open source and
      freely available at http://amplimethprofiler.sourceforge.net .

PMID- 27884102
TI  - Gene expression profile of intramuscular muscle in Nellore cattle with extreme
      values of fatty acid.
AB  - BACKGROUND: Fatty acid type in beef can be detrimental to human health and has
      received considerable attention in recent years. The aim of this study was to
      identify differentially expressed genes in longissimus thoracis muscle of 48
      Nellore young bulls with extreme phenotypes for fatty acid composition of
      intramuscular fat by RNA-seq technique. RESULTS: Differential expression analyses
      between animals with extreme phenotype for fatty acid composition showed a total
      of 13 differentially expressed genes for myristic (C14:0), 35 for palmitic
      (C16:0), 187 for stearic (C18:0), 371 for oleic (C18:1, cis-9), 24 for conjugated
      linoleic (C18:2 cis-9, trans11, CLA), 89 for linoleic (C18:2 cis-9,12 n6), and
      110 genes for alpha-linolenic (C18:3 n3) fatty acids. For the respective sums of
      the individual fatty acids, 51 differentially expressed genes for saturated fatty
      acids (SFA), 336 for monounsaturated (MUFA), 131 for polyunsaturated (PUFA), 92
      for PUFA/SFA ratio, 55 for omega3, 627 for omega6, and 22 for omega6/omega3 ratio
      were identified. Functional annotation analyses identified several genes
      associated with fatty acid metabolism, such as those involved in intra and extra
      cellular transport of fatty acid synthesis precursors in intramuscular fat of
      longissimus thoracis muscle. Some of them must be highlighted, such as: ACSM3 and
      ACSS1 genes, which work as a precursor in fatty acid synthesis; DGAT2 gene that
      acts in the deposition of saturated fat in the adipose tissue; GPP and LPL genes
      that support the synthesis of insulin, stimulating both the glucose synthesis and
      the amino acids entry into the cells; and the BDH1 gene, which is responsible for
      the synthesis and degradation of ketone bodies used in the synthesis of ATP.
      CONCLUSION: Several genes related to lipid metabolism and fatty acid composition
      were identified. These findings must contribute to the elucidation of the genetic
      basis to improve Nellore meat quality traits, with emphasis on human health.
      Additionally, it can also contribute to improve the knowledge of fatty acid
      biosynthesis and the selection of animals with better nutritional quality.

PMID- 27884104
TI  - Phylogeography reveals an ancient cryptic radiation in East-Asian tree frogs
      (Hyla japonica group) and complex relationships between continental and island
      lineages.
AB  - BACKGROUND: In contrast to the Western Palearctic and Nearctic biogeographic
      regions, the phylogeography of Eastern-Palearctic terrestrial vertebrates has
      received relatively little attention. In East Asia, tectonic events, along with
      Pleistocene climatic conditions, likely affected species distribution and
      diversity, especially through their impact on sea levels and the consequent
      opening and closing of land-bridges between Eurasia and the Japanese Archipelago.
      To better understand these effects, we sequenced mitochondrial and nuclear
      markers to determine phylogeographic patterns in East-Asian tree frogs, with a
      particular focus on the widespread H. japonica. RESULTS: We document several
      cryptic lineages within the currently recognized H. japonica populations,
      including two main clades of Late Miocene divergence (~5 Mya). One occurs on the
      northeastern Japanese Archipelago (Honshu and Hokkaido) and the Russian Far-East
      islands (Kunashir and Sakhalin), and the second one inhabits the remaining range,
      comprising southwestern Japan, the Korean Peninsula, Transiberian China, Russia
      and Mongolia. Each clade further features strong allopatric Plio-Pleistocene
      subdivisions (~2-3 Mya), especially among continental and southwestern Japanese
      tree frog populations. Combined with paleo-climate-based distribution models, the
      molecular data allowed the identification of Pleistocene glacial refugia and
      continental routes of postglacial recolonization. Phylogenetic reconstructions
      further supported genetic homogeneity between the Korean H. suweonensis and
      Chinese H. immaculata, suggesting the former to be a relic population of the
      latter that arose when the Yellow Sea formed, at the end of the last glaciation.
      CONCLUSIONS: Patterns of divergence and diversity were likely triggered by
      Miocene tectonic activities and Quaternary climatic fluctuations (including
      glaciations), causing the formation and disappearance of land-bridges between the
      Japanese islands and the continent. Overall, this resulted in a ring-like
      diversification of H. japonica around the Sea of Japan. Our findings urge for
      important taxonomic revisions in East-Asian tree frogs. First, they support the
      synonymy of H. suweonensis (Kuramoto, 1980) and H. immaculata (Boettger, 1888).
      Second, the nominal H. japonica (Gunther, 1859) represents at least two species:
      an eastern (new taxon A) on the northern Japanese and Russian Far East islands,
      and a southwestern species (n. t. B) on southern Japanese islands and possibly
      also forming continental populations. Third, these continental tree frogs may
      also represent an additional entity, previously described as H. stepheni
      Boulenger, 1888 (senior synonym of H. ussuriensis Nikolskii, 1918). A complete
      revision of this group requires further taxonomic and nomenclatural analyses,
      especially since it remains unclear to which taxon the species-epitheton japonica
      corresponds to.

PMID- 27884105
TI  - Structural features of DNA that determine RNA polymerase II core promoter.
AB  - BACKGROUND: The general structure and action of all eukaryotic and archaeal RNA
      polymerases machinery have an astonishing similarity despite the diversity of
      core promoter sequences in different species. The goal of our work is to find
      common characteristics of DNA region that define it as a promoter for the RNA
      polymerase II (Pol II). RESULTS: The profiles of a large number of physical and
      structural characteristics, averaged over representative sets of the Pol II
      minimal core promoters of the evolutionary divergent species from animals, plants
      and unicellular fungi were analysed. In addition to the characteristics defined
      at the base-pair steps, we, for the first time, use profiles of the ultrasonic
      cleavage and DNase I cleavage indexes, informative for internal properties of
      each complementary strand. CONCLUSIONS: DNA of the core promoters of metazoans
      and Schizosaccharomyces pombe has similar structural organization. Its mechanical
      and 3D structural characteristics have singular properties at the positions of
      TATA-box. The minor groove is broadened and conformational motion is decreased in
      that region. Special characteristics of conformational behavior are revealed in
      metazoans at the region, which connects the end of TATA-box and the transcription
      start site (TSS). The intensities of conformational motions in the complementary
      strands are periodically changed in opposite phases. They are noticeable, best of
      all, in mammals. Such conformational features are lacking in the core promoters
      of S. pombe. The profiles of Saccharomyces cerevisiae core promoters
      significantly differ: their singular region is shifted down thus pointing to the
      uniqueness of their structural organization. Obtained results may be useful in
      genetic engineering for artificial modulation of the promoter strength.

PMID- 27884106
TI  - SPECtre: a spectral coherence--based classifier of actively translated
      transcripts from ribosome profiling sequence data.
AB  - BACKGROUND: Active protein translation can be assessed and measured using
      ribosome profiling sequencing strategies. Prevailing analytical approaches
      applied to this technology make use of sequence fragment length profiling or
      reading frame occupancy enrichment to differentiate between active translation
      and background noise, however they do not consider additional characteristics
      inherent to the technology which limits their overall accuracy. RESULTS: Here, we
      present an analytical tool that models the overall tri-nucleotide periodicity of
      ribosomal occupancy using a classifier based on spectral coherence. Our software,
      SPECtre, examines the relationship of normalized ribosome profiling read coverage
      over a rolling series of windows along a transcript relative to an idealized
      reference signal without the matched requirement of mRNA-Seq. CONCLUSIONS: A
      comparison of SPECtre against previously published methods on existing data shows
      a marked improvement in accuracy for detecting active translation and exhibits
      overall high accuracy at a low false discovery rate. In addition, SPECtre
      performs comparably to a recently published method similarly based on spectral
      coherence, however with reduced runtime and memory requirements. SPECtre is
      available as an open source software package at https://github.com/mills
      lab/spectreok .

PMID- 27884107
TI  - Association between changes in cerebral grey matter volume and postoperative
      cognitive dysfunction in elderly patients: study protocol for a prospective
      observational cohort study.
AB  - BACKGROUND: Cognitive decline is frequently observed in elderly patients after
      major surgery. The pathophysiology of postoperative cognitive dysfunction (POCD)
      remains unclear. The aim of our investigation is to identify potential
      associations between brain volume change and POCD in elderly patients undergoing
      major surgery. METHODS: This is a prospective observational cohort study approved
      by the regional ethics board. We intend to compare specific brain volumes
      (hippocampus, lateral ventricle, total grey matter volume, regional cortical
      thickness) on magnetic resonance imaging and cognitive functions determined by a
      neuropsychological assessment battery in 70 study participants aged >=65 years
      before and 3 and 12 months after major noncardiac surgery. Thirty volunteers will
      be included as matched nonsurgical controls. The primary endpoint of the study is
      the change in hippocampal volume over time in patients with and without POCD. The
      secondary endpoint is the correlation between the change in cerebral volume and
      cognitive function. We will follow the STROBE guidelines for reporting the
      results of observational studies. DISCUSSION: We hypothesize that surgery under
      general anesthesia is associated with a loss of cerebral grey matter, and that
      the degree of postoperative cognitive dysfunction correlates with the extent of
      atrophy in areas of the brain that are relevant for cognitive functions. The
      validation of reproducible anatomical biomarkers, such as the specific brain
      volumes examined in our cohort, may serve to evaluate the effect of preventive
      strategies and treatment interventions for POCD in follow-up studies. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT02045004 . Registered 22 January 2014.
      Kofam.ch SNCTP000001751. Registered 21 April 2016 (retrospectively registered).

PMID- 27884108
TI  - Characterization and management of long runs of homozygosity in parental nucleus
      lines and their associated crossbred progeny.
AB  - BACKGROUND: In nucleus populations, regions of the genome that have a high
      frequency of runs of homozygosity (ROH) occur and are associated with a reduction
      in genetic diversity, as well as adverse effects on fitness. It is currently
      unclear whether, and to what extent, ROH stretches persist in the crossbred
      genome and how genomic management in the nucleus population might impact low
      diversity regions and its implications on the crossbred genome. METHODS: We
      calculated a ROH statistic based on lengths of 5 (ROH5) or 10 (ROH10) Mb across
      the genome for genotyped Landrace (LA), Large White (LW) and Duroc (DU) dams. We
      simulated crossbred dam (LA * LW) and market [DU * (LA * LW)] animal genotypes
      based on observed parental genotypes and the ROH frequency was tabulated. We
      conducted a simulation using observed genotypes to determine the impact of
      minimizing parental relationships on multiple diversity metrics within nucleus
      herds, i.e. pedigree-(A), SNP-by-SNP relationship matrix or ROH relationship
      matrix. Genome-wide metrics included, pedigree inbreeding, heterozygosity and
      proportion of the genome in ROH of at least 5 Mb. Lastly, the genome was split
      into bins of increasing ROH5 frequency and, within each bin, heterozygosity, ROH5
      and length (Mb) of ROH were evaluated. RESULTS: We detected regions showing high
      frequencies of either ROH5 and/or ROH10 across both LW and LA on SSC1, SSC4, and
      SSC14, and across all breeds on SSC9. Long haplotypes were shared across parental
      breeds and thus, regions of ROH persisted in crossbred animals. Averaged across
      replicates and breeds, progeny had higher levels of heterozygosity (0.0056 +/-
      0.002%) and lower proportion of the genome in a ROH of at least 5 Mb (-0.015 +/-
      0.003%) than their parental genomes when genomic relationships were constrained,
      while pedigree relationships resulted in negligible differences at the genomic
      level. Across all breeds, only genomic data was able to target low diversity
      regions. CONCLUSIONS: We show that long stretches of ROH present in the parents
      persist in crossbred animals. Furthermore, compared to using pedigree
      relationships, using genomic information to constrain parental relationships
      resulted in maintaining more genetic diversity and more effectively targeted low
      diversity regions.

PMID- 27884109
TI  - Cloning, functional expression and characterization of a bifunctional 3
      hydroxybutanal dehydrogenase /reductase involved in acetone metabolism by
      Desulfococcus biacutus.
AB  - BACKGROUND: The strictly anaerobic, sulfate-reducing bacterium Desulfococcus
      biacutus can utilize acetone as sole carbon and energy source for growth. Whereas
      in aerobic and nitrate-reducing bacteria acetone is activated by carboxylation
      with CO2 to acetoacetate, D. biacutus involves CO as a cosubstrate for acetone
      activation through a different, so far unknown pathway. Proteomic studies
      indicated that, among others, a predicted medium-chain dehydrogenase/reductase
      (MDR) superfamily, zinc-dependent alcohol dehydrogenase (locus tag
      DebiaDRAFT_04514) is specifically and highly produced during growth with acetone.
      RESULTS: The MDR gene DebiaDRAFT_04514 was cloned and overexpressed in E. coli.
      The purified recombinant protein required zinc as cofactor, and accepted
      NADH/NAD+ but not NADPH/NADP+ as electron donor/acceptor. The pH optimum was at
      pH 8, and the temperature optimum at 45  degrees C. Highest specific activities
      were observed for reduction of C3 - C5-aldehydes with NADH, such as propanal to
      propanol (380 +/- 15 mU mg-1 protein), butanal to butanol (300 +/- 24 mU mg-1),
      and 3-hydroxybutanal to 1,3-butanediol (248 +/- 60 mU mg-1), however, the enzyme
      also oxidized 3-hydroxybutanal with NAD+ to acetoacetaldehyde (83 +/- 18 mU mg
      1). CONCLUSION: The enzyme might play a key role in acetone degradation by D.
      biacutus, for example as a bifunctional 3-hydroxybutanal dehydrogenase/reductase.
      Its recombinant production may represent an important step in the elucidation of
      the complete degradation pathway.

PMID- 27884112
TI  - Erratum to: Genetic analysis of intestinal polyp development in Collaborative
      Cross mice carrying the Apc Min/+ mutation.

PMID- 27884111
TI  - Quantitative genetic analysis of the bTB diagnostic single intradermal
      comparative cervical test (SICCT).
AB  - BACKGROUND: Bovine tuberculosis (bTB) is a disease of significant economic
      importance and is a persistent animal health problem with implications for public
      health worldwide. Control of bTB in the UK has relied on diagnosis through the
      single intradermal comparative cervical test (SICCT). However, limitations in the
      sensitivity of this test hinder successful eradication and the control of bTB
      remains a major challenge. Genetic selection for cattle that are more resistant
      to bTB infection can assist in bTB control. The aim of this study was to conduct
      a quantitative genetic analysis of SICCT measurements collected during bTB herd
      testing. Genetic selection for bTB resistance will be partially informed by SICCT
      based diagnosis; therefore it is important to know whether, in addition to
      increasing bTB resistance, this might also alter genetically the epidemiological
      characteristics of SICCT. RESULTS: Our main findings are that: (1) the SICCT test
      is robust at the genetic level, since its hierarchy and comparative nature
      provide substantial protection against random genetic changes that arise from
      genetic drift and from correlated responses among its components due to either
      natural or artificial selection; (2) the comparative nature of SICCT provides
      effective control for initial skin thickness and age-dependent differences; and
      (3) continuous variation in SICCT is only lowly heritable and has a weak
      correlation with SICCT positivity among healthy animals which was not
      significantly different from zero (P > 0.05). These emerging results demonstrate
      that genetic selection for bTB resistance is unlikely to change the probability
      of correctly identifying non-infected animals, i.e. the test's specificity, while
      reducing the overall number of cases. CONCLUSIONS: This study cannot exclude all
      theoretical risks from selection on resistance to bTB infection but the role of
      SICCT in disease control is unlikely to be rapidly undermined, with any adverse
      correlated responses expected to be weak and slow, which allow them to be
      monitored and managed.

PMID- 27884110
TI  - Tsetse fly tolerance to T. brucei infection: transcriptome analysis of
      trypanosome-associated changes in the tsetse fly salivary gland.
AB  - BACKGROUND: For their transmission, African trypanosomes rely on their blood
      feeding insect vector, the tsetse fly (Glossina sp.). The ingested Trypanosoma
      brucei parasites have to overcome a series of barriers in the tsetse fly
      alimentary tract to finally develop into the infective metacyclic forms in the
      salivary glands that are transmitted to a mammalian host by the tsetse bite. The
      parasite population in the salivary gland is dense with a significant number of
      trypanosomes tightly attached to the epithelial cells. Our current knowledge on
      the impact of the infection on the salivary gland functioning is very limited.
      Therefore, this study aimed to gain a deeper insight into the global gene
      expression changes in the salivary glands of Glossina morsitans morsitans in
      response to an infection with the T. brucei parasite. A detailed whole
      transcriptome comparison of midgut-infected tsetse with and without a mature
      salivary gland infection was performed to study the impact of a trypanosome
      infection on different aspects of the salivary gland functioning and the
      mechanisms that are induced in this tissue to tolerate the infection i.e. to
      control the negative impact of the parasite presence. Moreover, a transcriptome
      comparison with age-matched uninfected flies was done to see whether gene
      expression in the salivary glands is already affected by a trypanosome infection
      in the tsetse midgut. RESULTS: By a RNA-sequencing (RNA-seq) approach we compared
      the whole transcriptomes of flies with a T. brucei salivary gland/midgut
      infection versus flies with only a midgut infection or versus non-infected flies,
      all with the same age and feeding history. More than 7500 salivary gland
      transcripts were detected from which a core group of 1214 differentially
      expressed genes (768 up- and 446 down-regulated) were shared between the two
      transcriptional comparisons. Gene Ontology enrichment analysis and detailed gene
      expression comparisons showed a diverse impact at the gene transcript level.
      Increased expression was observed for transcripts encoding for proteins involved
      in immunity (like several genes of the Imd-signaling pathway, serine proteases,
      serpins and thioester-containing proteins), detoxification of reactive species,
      cell death, cytoskeleton organization, cell junction and repair. Decreased
      expression was observed for transcripts encoding the major secreted proteins such
      as 5'-nucleotidases, adenosine deaminases and the nucleic acid binding proteins
      Tsals. Moreover, expression of some gene categories in the salivary glands were
      found to be already affected by a trypanosome midgut infection, before the
      parasite reaches the salivary glands. CONCLUSIONS: This study reveals that the T.
      brucei population in the tsetse salivary gland has a negative impact on its
      functioning and on the integrity of the gland epithelium. Our RNA-seq data
      suggest induction of a strong local tissue response in order to control the
      epithelial cell damage, the ROS intoxication of the cellular environment and the
      parasite infection, resulting in the fly tolerance to the infection. The modified
      expression of some gene categories in the tsetse salivary glands by a trypanosome
      infection at the midgut level indicate a putative anticipatory response in the
      salivary glands, before the parasite reaches this tissue.

PMID- 27884114
TI  - Hyperemesis gravidarum and placental dysfunction disorders.
AB  - BACKGROUND: Evidence about the consequence of hyperemesis gravidarum (HG) on
      pregnancy outcomes is still inconclusive. In this study, we evaluated if
      occurrence of hyperemesis gravidarum is associated with placental dysfunction
      disorders and neonatal outcomes. METHODS: A prospective cohort study was
      conducted in a maternal and child health primary care referral center, Budi
      Kemuliaan Hospital and its branch, in Jakarta, Indonesia. 2252 pregnant women
      visiting the hospital for regular antenatal care visits from July 2012 until
      October 2014 were included at their first clinic visit. For women without, with
      mild and with severe hyperemesis, placental dysfunction disorders (gestational
      hypertension, preeclampsia (PE), stillbirth, miscarriage), neonatal outcomes
      (birth weight, small for gestational age (SGA), low birth weight (LBW), Apgar
      score at 5 min, gestational age at delivery) and placental outcomes (placental
      weight and placental-weight-to-birth-weight ratio (PW/BW ratio)) were studied.
      RESULTS: Compared to newborns of women without hyperemesis, newborns of women
      with severe hyperemesis had a 172 g lower birth weight in adjusted analysis
      (95%CI -333.26; -10.18; p = 0.04). There were no statistically significant
      effects on placental dysfunction disorders or other neonatal outcome measures.
      CONCLUSIONS: The results of our study suggest that hyperemesis gravidarum does
      not seem to induce placental dysfunction disorders, but does, if severe lead to
      lower birth weight.

PMID- 27884113
TI  - Disrupting ROS-protection mechanism allows hydrogen peroxide to accumulate and
      oxidize Sb(III) to Sb(V) in Pseudomonas stutzeri TS44.
AB  - BACKGROUND: Microbial antimonite [Sb(III)] oxidation converts toxic Sb(III) into
      less toxic antimonate [Sb(V)] and plays an important role in the biogeochemical
      Sb cycle. Currently, little is known about the mechanisms underlying bacterial
      Sb(III) resistance and oxidation. RESULTS: In this study, Tn5 transposon
      mutagenesis was conducted in the Sb(III)-oxidizing strain Pseudomonas stutzeri
      TS44 to isolate the genes responsible for Sb(III) resistance and oxidation. An
      insertion mutation into gshA, encoding a glutamate cysteine ligase involved in
      glutathione biosynthesis, generated a strain called P. stutzeri TS44-gshA540.
      This mutant strain was complemented with a plasmid carrying gshA to generate
      strain P. stutzeri TS44-gshA-C. The transcription of gshA, the two superoxide
      dismutase (SOD)-encoding genes sodB and sodC as well as the catalase-encoding
      gene katE was monitored because gshA-encoded glutamate cysteine ligase is
      responsible for the biosynthesis of glutathione (GSH) and involved in the
      cellular stress defense system as are superoxide dismutase and catalase
      responsible for the conversion of ROS. In addition, the cellular content of total
      ROS and in particular H2O2 was analyzed. Compared to the wild type P. stutzeri
      TS44 and TS44-gshA-C, the mutant P. stutzeri TS44-gshA540 had a lower GSH content
      and exhibited an increased content of total ROS and H2O2 and increased the
      Sb(III) oxidation rate. Furthermore, the transcription of sodB, sodC and katE was
      induced by Sb(III). A positive linear correlation was found between the Sb(III)
      oxidation rate and the H2O2 content (R 2 = 0.97), indicating that the accumulated
      H2O2 is correlated to the increased Sb(III) oxidation rate. CONCLUSIONS: Based on
      the results, we propose that a disruption of the pathway involved in ROS
      protection allowed H2O2 to accumulate. In addition to the previously reported
      enzyme mediated Sb(III) oxidation, the mechanism of bacterial oxidation of
      Sb(III) to Sb(V) includes a non-enzymatic mediated step using H2O2 as the
      oxidant.

PMID- 27884115
TI  - Chemical shift MR imaging in the lumbar vertebra: the effect of field strength,
      scanner vendors and flip angles in repeatability of signal intensity index
      measurement.
AB  - BACKGROUND: To evaluate the reproducibility of signal intensity index (SII)
      measurements with MRI systems from different vendors and with different field
      strengths, and to test the effectiveness of flip angle. METHODS: Thirty-two
      healthy volunteers (mean age 35.3 +/- 9.3 years) were enrolled in this ethics
      committee-approved study. Chemical shift MR imaging was performed on 1.5- and 3.0
      T MR systems from three vendors. Two independent observers measured SII values in
      five lumbar segments. Inter- and intraobserver agreement was assessed using the
      interclass correlation coefficients (ICCs). Differences of mean SII values
      between different field strengths and MR vendors as well as flip angles were
      compared by using repeated-measures analysis of variance. Differences of mean SII
      values between different flip angles were also compared by using paired-sample t
      test. RESULTS: Inter- and intra-observer correlation coefficients showed good
      agreement (all ICC > 0.75) when measuring SII values at different MR systems
      (ICCs ranging from 0.896 to 0.983) and flip angles (ICCs ranging from 0.824 to
      0.983). There were no significant differences in mean SII values measured by
      different MR vendors with different field strengths (all p > 0.05 ranging from
      0.337 to 0.824). The differences in the mean SII between the four different flip
      angles were statistically significant (all p < 0.05 ranging from < 0.001 to
      0.004) except the group of flip angle 50 degrees  versus 70 degrees  (p = 0.116).
      CONCLUSION: The SII measurement using chemical shift MR imaging may be comparable
      between different MR systems. Also high flip angles showed better stability to
      quantitate lumbar fat content.

PMID- 27884117
TI  - Erratum to: Hospitalization costs for community-acquired pneumonia in Dutch
      elderly: an observational study.

PMID- 27884116
TI  - Kidney disease in the elderly: biopsy based data from 14 renal centers in Poland.
AB  - BACKGROUND: Longer life expectancy is associated with an increasing prevalence of
      kidney disease. Aging itself may cause renal damage, but the spectrum of kidney
      disorders that affect elderly patients is diverse. Few studies, mostly form US,
      Asia and West Europe found differences in the prevalence of some types of kidney
      diseases between elderly and younger patients based on renal biopsy findings,
      with varied proportion between glomerulopathies and arterionephrosclerosis as a
      dominant injury found. Here, for the first time in Eastern Europe we analyzed
      native kidney biopsy findings and their relationship to clinical characteristics
      at the time of biopsy in elderly individuals (aged >=65) in comparison to younger
      adults (aged 18-64). METHODS: Biopsy and clinical data from 352 patients aged
      >=65 were retrospectively identified, analyzed and compared with a control group
      of 2214 individuals aged 18-64. All kidney biopsies studied were examined at
      Medical University of Warsaw in years 2009-14. RESULTS: In elderly patients the
      leading indication for biopsy was nephrotic range proteinuria without hematuria
      (34.2%) and the most prevalent pathologic diagnoses were: membranous
      glomerulonephritis (MGN) (18.2%), focal segmental glomerulosclerosis (FSGS)
      (17.3%) amyloidosis (13.9%) and pauci immune glomerulonephritis (12.8%).
      Hypertension and age-related lesions very rarely were found an exclusive or
      dominant finding in a kidney biopsy (1.7%) and a cause of proteinuria (1.1%) in
      elderly individuals. There were 18.2% diabetics among elderly individuals, and as
      much as 75% of them had no morphologic signs of diabetic kidney disease in the
      renal biopsy. Amyloidosis, MGN, pauci immune GN, crescentic GN and light and/or
      heavy chain deposition disease (LCDD/HCDD) were more frequent whereas IgA
      nephropathy (IgAN), lupus nephritis (LN) and thin basement membrane disease
      (TBMD) were less common among elderly than in younger patients. CONCLUSIONS:
      Proteinuria, a dominating manifestation in elderly patients subjected to kidney
      biopsy was most commonly related to glomerulopathies. The relatively high
      prevalence of potentially curative kidney diseases in elderly individuals
      implicates the importance of renal biopsy in these patients.

PMID- 27884118
TI  - Burden of Clostridium difficile-associated disease among patients residing in
      nursing homes: a population-based cohort study.
AB  - BACKGROUND: Clostridium difficile (C. difficile) infection (CDI) is the leading
      cause of nosocomial diarrhea in the United States. This study aimed to examine
      the incidence of CDI and evaluate mortality and economic burden of CDI in an
      elderly population who reside in nursing homes (NHs). METHODS: This was a
      population-based retrospective cohort study focusing on US NHs by linking
      Medicare 5% sample, Medicaid, Minimum Data Set (MDS) (2008-10). NH residents aged
      >=65 years with continuous enrollment in Medicare and/or Medicaid Fee-for-Service
      plan for >=12 months and >=2 quarterly MDS assessments were eligible for the
      study. The incidence rate was calculated as the number of CDI episodes by 100,000
      person-years. A 1:4 propensity score matched sample of cohorts with and without
      CDI was generated to assess mortality and health care costs following the first
      CDI. RESULTS: Among 32,807 NH residents, 941 residents had >=1 episode of CDI in
      2009, with an incidence of 3359.9 per 100,000 person-years. About 30% CDI
      episodes occurred in the hospital setting. NH residents with CDI (vs without CDI)
      were more likely to have congestive heart failure, renal disease, cerebrovascular
      disease, hospitalizations, and outpatient antibiotic use. During the follow-up
      period, the 30-day (14.7% vs 4.3%, P < 0.001), 60-day (22.7% vs 7.5%, P < 0.001),
      6-month (36.3% vs 18.3%, P < 0.001), and 1-year mortality rates (48.2% vs 31.1%,
      P < 0.001) were significantly higher among the CDI residents vs non-CDI
      residents. Total health care costs within 2 months following the first CDI
      episode were also significantly higher for CDI residents ($28,621 vs $13,644, P <
      0.001). CONCLUSIONS: CDI presents a serious public health issue in NHs.
      Mortality, health care utilization, and associated costs were significant
      following incident CDI episodes.

PMID- 27884119
TI  - Anti-LRP/LR-specific antibody IgG1-iS18 impedes adhesion and invasion of
      pancreatic cancer and neuroblastoma cells.
AB  - BACKGROUND: Cancer has become a global burden due to its high incidence and
      mortality rates, with an estimated 14.1 million cancer cases reported worldwide
      in 2012 particularly as a result of metastasis. Metastasis involves two crucial
      steps: adhesion and invasion, and the non-integrin receptor; the 37-kDa/67-kDa
      laminin receptor precursor/ high affinity laminin receptor (LRP/LR) has been
      shown to be overexpressed on the surface of tumorigenic cells, thus being
      implicated in the enhancement of these two crucial steps. The current study
      investigated the role of LRP/LR on the aggressiveness of pancreatic cancer (AsPC
      1) and neuroblastoma (IMR-32) cells with respect to their adhesive and invasive
      potential. METHODS: AsPC-1 and IMR-32 cells were utilized as the experimental
      cell lines for the study. Cell surface LRP/LR levels were visualised and
      quantified on the experimental and control (MCF-7) cell lines via confocal
      microscopy and flow cytometry, respectively. Total LRP/LR levels in the cell
      lines were assessed by Western blotting and the adhesive and invasive potential
      of the above-mentioned cell lines was determined before and after supplementation
      with the anti-LRP/LR specific antibody IgG1-iS18. Statistical significance of the
      data was confirmed via the use of the two-tailed student's t-test and Pearson's
      correlation coefficient. RESULTS: Flow cytometry revealed that AsPC-1 and IMR-32
      cells displayed significantly higher cell surface LRP/LR levels in comparison to
      the MCF-7 control cell line. However, Western blotting and subsequent
      densitometric analysis revealed that all three tumorigenic cell lines displayed
      no significant difference in total LRP/LR levels. The treatment of AsPC-1 and IMR
      32 cells with IgG1-iS18 caused a significant reduction in the adhesive and
      invasive potential of the cells to laminin-1 and through the ECM-like MatrigelTM,
      respectively. Pearson's correlation coefficients indicated a high correlation,
      thus suggesting a directly proportional relationship between cell surface LRP/LR
      levels and the adhesive and invasive potential of AsPC-1 and IMR-32 cells.
      CONCLUSION: These findings suggest that through the interference of the LRP/LR
      laminin-1 interaction, the anti-LRP/LR specific antibody IgG1-iS18 may act as an
      alternative therapeutic tool for the treatment of metastatic pancreatic cancer
      and neuroblastoma.

PMID- 27884120
TI  - Removal of free light chains in hemodialysis patients without multiple myeloma: a
      crossover comparison of three different dialyzers.
AB  - BACKGROUND: Immunoglobulin light chains are classified as middle molecule uremic
      toxins able to interact with B lymphocyte membranes leading to the activation of
      transmembrane signaling. The ensuing impairment of neutrophil function can
      contribute to the chronic inflammation state of uremic patients, and the
      increased risk of bacterial infections or vascular calcifications. The aim of
      this crossover observational study was to assess the difference in free light
      chain removal by three different hemodialysis filters in patients not affected by
      multiple myeloma. METHODS: Free light chain removal was compared in the
      polymethylmethacrylate (PMMA) membrane Filtryzer BK-F, the polyphenylene HFR17
      filter and the conventional polysulfone filter F7HPS. Twenty chronic hemodialysis
      patients were enrolled: mean age was 67.7 +/- 17.0 years, M/F = 14/6, dialysis
      vintage (months) 25.5 +/- 32.0. The patients were randomized into two groups of
      treatment lasting 6 weeks each. The dialysis sessions checked were the midweek
      sessions and the blood was drawn at times 0, 120' and 240'. Kappa (k) and lambda
      (lambda) light chain levels, beta2microglobulin (beta2M), C reactive protein
      (CRP) and albumin were checked. RESULTS: K light chain levels were 345.0 +/-
      100.0 mg/L, lambda light chains were 121.4 +/- 27.0 mg/L. The values of k light
      chains at times 120' and 240' were significantly lower with PMMA and HFR17 than
      those obtained with F7. The reduction ratio per session (RRs) for k light chains
      was 44.1 +/- 4.3% with HFR17, 55.3 +/- 3.4% with PMMA, 25.7 +/- 8.3% with F7 (p =
      0.018). The RRs for lambda light chains was 30.3 +/- 2.9% with HFR17, 37.8 +/-
      17.3% with PMMA, 14.0 +/- 3.9% with F7 (p = 0.032). As to beta2M, RRs was 42.4 +/
      3.2% with HFR17 vs. 33.9 +/- 2.8% with PMMA vs. 6.3 +/- 1.9% with F7 (p =
      0.022). The three filters tested showed no differences in CRP or albumin levels.
      CONCLUSION: In terms of light chain and beta2M removal, the PMMA and on-line HFR
      filters are similar and both are significantly more effective than the F7 filter
      in chronic dialysis patients. TRIAL REGISTRATION: The present trial was
      registered retrospectively ( NCT02950389 , 31/10/2016).

PMID- 27884121
TI  - Prevalence and risk factors of intestinal protozoan infections: a population
      based study in rural areas of Boyer-Ahmad district, Southwestern Iran.
AB  - BACKGROUND: Parasitic infections are still a significant health problem in rural
      areas in developing countries including Iran. There is no recent population-based
      data about the prevalence of human intestinal parasites in most rural areas of
      Iran. The current study aimed to determine the prevalence of intestinal protozoan
      infection in inhabitants of rural areas of Boyer-Ahmad district, Southwestern
      Iran. METHODS: A total of 1025 stool samples were collected from the inhabitant
      of 50 randomly selected villages in Boyer-Ahmad Township. The stool samples were
      evaluated by parasitological methods including, direct wet-mounting, formalin
      ethyl acetate concentration, zinc sulfate floatation, and Trichrome permanent
      stain for detection of protozoan infections. Diarrheic samples were further
      evaluated with a modified Ziehl-Neelsen staining method for detection of
      coccidian parasites. RESULTS: The prevalence of both pathogenic and nonpathogenic
      intestinal parasites in the population was 37.5% (385 out of 1025 cases), some
      individual with multiple infections. Giardia lamblia was detected in 179
      (17.46%), Blastocystis hominis in 182 (17.76%), Entamoeba histolytica/dispar in 9
      (0.87%), Endolimax nana in 216 (21.07%), Entamoeba coli in 151 (14.73%),
      Ioedamoeba butschlii in 45 (4.39%), Chillomastix mesnili in 22 (2.14%),
      Trichomonas hominis in 2 (0.19%) and Dientamoeba fragillis in 2 (0.19%) of cases.
      Multivariate logistic regression revealed significant associations between
      protozoan infection (pathogenic protozoa) and contact with animals (OR yes/no =
      2.22, p < 0.001) and educational status (OR higher/illiterate = 0.40, P = 0.01).
      CONCLUSION: Findings of this study demonstrated that protozoan infection rate in
      rural areas of southwestern Iran is still high and remained as a challenging
      health problem in these areas.

PMID- 27884123
TI  - The Spanish version of the Childbirth Experience Questionnaire (CEQ-E):
      reliability and validity assessment.
AB  - BACKGROUND: The Childbirth Experience Questionnaire (CEQ) was originally designed
      to study women's perceptions of labour and birth. The main objective of our study
      was to adapt the CEQ to the Spanish context and determine its psychometric
      properties. This would provide an opportunity to evaluate women's experiences in
      order to improve evidence in the Spanish context as recommended by national
      guidelines. METHODS: The CEQ was translated into Spanish using a standard forward
      and back translation method (CEQ-E). A convenience sample of 364 women was
      recruited from 3 Spanish hospitals; all participants were able to read and write
      in Spanish. Mothers with high risk pregnancies or preterm deliveries were
      excluded from the study. A self-administered questionnaire on sociodemographic
      variables was completed by participants before discharge. Data on childbirth
      variables were obtained from maternity records. Between 1 and 3 months postpartum
      a postal CEQ-E questionnaire was sent. The CEQ-E structure was examined by a
      confirmatory factor analysis of polychoric correlations using a diagonally
      weighted least squares estimator. Reliability was assessed using Cronbach's
      alpha. Construct validity was conducted by testing differences in CEQ-E scores
      between known-groups (to differ on key variables). RESULTS: 226 (62.1%) of the
      recruited participants completed the postal questionnaire. The CEQ-E factor
      structure was similar to the original one. The Spanish version showed fit
      statistics in line with standard recommendations: CFI = 0.97; NNFI = 0.97; RMSEA
      = 0.066; SRMS = 0.077. The internal consistency reliability of the CEQ-E was good
      for the overall scale (0.88) and for all subscales (0.80, 0.90, 0.76, 0.68 for
      "own capacity", "professional support", "perceived safety" and "participation",
      respectively) and similar to the original version. Women with a labour duration
      <= 12 h, women with a labour not induced, women with a normal birth and
      multiparous women showed higher overall CEQ-E scores and "perceived safety"
      subscale scores. Women with a labour duration <= 12 h and those with previous
      experience of labour obtained higher scores for the "own capacity" and
      "participation" subscales. CONCLUSIONS: The results of this study indicate that
      the CEQ-E can be considered a valid and reliable measure of women's perceptions
      of labour and birth in Spain.

PMID- 27884122
TI  - Assessment of copy number variations in 120 patients with Poland syndrome.
AB  - BACKGROUND: Poland Syndrome (PS) is a rare congenital disorder presenting with
      agenesis/hypoplasia of the pectoralis major muscle variably associated with
      thoracic and/or upper limb anomalies. Most cases are sporadic, but familial
      recurrence, with different inheritance patterns, has been observed. The genetic
      etiology of PS remains unknown. Karyotyping and array-comparative genomic
      hybridization (CGH) analyses can identify genomic imbalances that can clarify the
      genetic etiology of congenital and neurodevelopmental disorders. We previously
      reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia
      and skeletal anomalies, and a chromosome six deletion in a patient presenting a
      complex phenotype that included pectoralis muscle hypoplasia. However, the
      contribution of genomic imbalances to PS remains largely unknown. METHODS: To
      investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic
      and array-CGH analyses were performed in 120 PS patients. RESULTS: Following the
      application of stringent filter criteria, 14 rare copy number variations (CNVs)
      were identified in 14 PS patients in different regions outside known common copy
      number variations: seven genomic duplications and seven genomic deletions,
      enclosing the two previously reported PS associated chromosomal deletions. These
      CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH
      data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA
      binding and apoptosis processes. The analysis also provided a number of candidate
      genes possibly causing the developmental defects observed in PS patients, among
      others REV3L, a gene coding for an error-prone DNA polymerase previously
      associated with Mobius Syndrome with variable phenotypes including pectoralis
      muscle agenesis. CONCLUSIONS: A number of rare CNVs were identified in PS
      patients, and these involve genes that represent candidates for further
      evaluation. Rare inherited CNVs may contribute to, or represent risk factors of
      PS in a multifactorial mode of inheritance.

PMID- 27884124
TI  - Community-based interventions to enhance knowledge, protective attitudes and
      behaviors towards canine rabies: results from a health communication intervention
      study in Guangxi, China.
AB  - BACKGROUND: In China canine rabies poses a serious public health problem in that
      human mortality ranks the second highest globally. While rabies health education
      interventions are advocated by WHO to be critical components of modern rabies
      control and prevention programs, available studies have not adequately
      investigated the relative efficacy of their implementation in at-risk
      populations. This study aims to measure and compare the effect on knowledge and
      protective behavior towards rabies of health education interventions that include
      a novel Short Messaging Service via cell phone (SMS) and rabies health
      information sessions (IS). METHODS: The study used a between-subject design
      involving repeated measures of rabies-related KAP (knowledge, attitude and
      practice). A total of 350 randomly selected villagers were randomly allocated
      into three intervention (SMS, IS and SMS + IS) and one control group. The content
      of SMS and IS covered topics about rabies prevention and route of transmission.
      The SMS intervention consisted of ten separate messages delivered three times two
      weeks after the pretest; the IS intervention was conducted once immediately after
      the pretest. A validated questionnaire was used to capture demographic
      information and KAP information. Ordinary Least Squares regression was used to
      contrast the effects of interventions. RESULTS: Our results indicate that overall
      SMS outperforms IS at improving knowledge and protective behavior against rabies.
      Our results suggest that a combined intervention of SMS and IS can result in
      higher scores than any of the two in isolation. The impact of SMS, IS and SMS +
      IS is greatest on knowledge, followed by attitude and practice scores.
      CONCLUSION: This study demonstrated that health communication modes based on SMS,
      IS and a combination of the two are all effective to improve rabies-related KAP
      in the short term. These findings highlight the potential usefulness of SMS as an
      additional tool for public health communication and promotion; further studies
      are needed to investigate the long term benefits of these interventions on the
      reduction of dog bites and resulting human rabies incidence.

PMID- 27884125
TI  - Epidemiology of and risk factors for neonatal candidemia at a tertiary care
      hospital in western China.
AB  - BACKGROUND: The prevalence and clinical characteristics of neonatal candidemia
      are poorly understood in western China. The aim of our study was to evaluate the
      epidemiological features of neonatal candidemia in the Liuzhou Maternity and
      Child Healthcare Hospital. METHODS: A retrospective case-control study was
      conducted between January 2012 and November 2015. Electronic databases were
      reviewed and data on Candida species were isolated from blood cultures and
      candidemia incidence, risk factors, and mortality were extracted. Univariate and
      multivariate logistic regression analysis were performed to identify risk factors
      associated with candidemia. RESULTS: During the 4-year period, candidemia was
      identified in 69 newborns, for an incidence rate of 13.6 per 1000 admissions.
      Prolonged antibiotic therapy duration [odds ratio (OR), 95% confidence incidence
      (95% CI) = 1.06, 1.01-1.10], total parenteral nutrition [OR, 95% CI = 6.03, 2.10
      17.30] and neurodevelopmental impairment (OR, 95% CI = 7.34, 1.18-45.80) were all
      associated with increased odds of candidemia development in infants (P value was
      0.010, 0.001, 0.033, respectively). The overall mortality rate was 7.2% in the
      candidemia group. CONCLUSIONS: Prolonged duration of antibiotic therapy, presence
      of total parenteral nutrition and neurodevelopmental impairment were the major
      risk factors associated with neonatal candidemia. This study highlights the
      importance of the early detection, diagnosis and treatment of neonatal
      candidemia.

PMID- 27884126
TI  - Help seeking behavior and onset-to-alarm time in patients with acute stroke: sub
      study of the preventive antibiotics in stroke study.
AB  - BACKGROUND: Patients with acute stroke often do not seek immediate medical help,
      which is assumed to be driven by lack of knowledge of stroke symptoms. We
      explored the process of help seeking behavior in patients with acute stroke,
      evaluating knowledge about stroke symptoms, socio-demographic and clinical
      characteristics, and onset-to-alarm time (OAT). METHODS: In a sub-study of the
      Preventive Antibiotics in Stroke Study (PASS), 161 acute stroke patients were
      prospectively included in 3 Dutch hospitals. A semi-structured questionnaire was
      used to assess knowledge, recognition and interpretation of stroke symptoms. With
      in-depth interviews, response actions and reasons were explored. OAT was recorded
      and associations with socio-demographic, clinical parameters were assessed.
      RESULTS: Knowledge about stroke symptoms does not always result in correct
      recognition of own stroke symptoms, neither into correct interpretation of the
      situation and subsequent action. In our study population of 161 patients with
      acute stroke, median OAT was 30 min (interquartile range [IQR] 10-150 min).
      Recognition of one-sided weakness and/or sensory loss (p = 0.046) and adequate
      interpretation of the stroke situation (p = 0.003), stroke at daytime (p =
      0.002), severe stroke (p = 0.003), calling the emergency telephone number (p =
      0.004), and transport by ambulance (p = 0.040) were associated with shorter OAT.
      CONCLUSION: Help seeking behavior after acute stroke is a complex process. A
      shorter OAT after stroke is associated with correct recognition of one-sided
      weakness and/or sensory loss, adequate interpretation of the stroke situation by
      the patient and stroke characteristics and logistics of stroke care, but not by
      knowledge of stroke symptoms.

PMID- 27884127
TI  - Cancer-related fatigue in post-treatment cancer survivors: application of the
      common sense model of illness representations.
AB  - BACKGROUND: Cancer-related fatigue (CrF) is a common and disruptive symptom that
      may be experienced during and after cancer. Research into the subjective
      experience of fatigue in this group is required. The common sense model of self
      regulation of health and illness (SRM) addresses personal beliefs or mental
      representations-whether medically sound or unsubstantiated- that a person holds
      about a health issue. The current study assesses if the SRM could be used as a
      theoretical framework for organizing the experiences of people with CrF, with a
      view to identifying methods to address fatigue in cancer survivors. METHOD: Four
      focus groups were held with a total of 18 cancer survivors who reported they
      experienced 'significant fatigue or reduced energy.' A thematic analysis was
      conducted within the framework of the SRM. RESULTS: Findings were aligned with
      the SRM, with participants discussing fatigue with reference to representation,
      coping, and appraisal of symptoms. In particular, the wider social context of CrF
      was frequently addressed. Perceived inadequacies in support available to those
      with lingering fatigue after the completion of cancer treatment were highlighted
      by the participants. CONCLUSION: This study explored the subjective experience of
      fatigue after cancer using the SRM. CrF should be approached as a complex
      psychosocial issue and considered from the patient perspective to facilitate
      better understanding and management of symptoms. The SRM is an applicable
      framework for identifying modifiable factors that could lead to improved coping
      with CrF in post-treatment cancer survivors.

PMID- 27884129
TI  - In Vivo optical coherence tomography visualization of intraplaque
      neovascularization at the site of coronary vasospasm: a case report.
AB  - BACKGROUND: Coronary plaques in patients with coronary vasospastic angina have
      been characterized by diffuse intima-media thickening with homogeneous fibrous
      tissue, without confluent necrotic tissue. However, coronary vasospasm can
      trigger coronary thrombosis, and may play an important role in the pathogenesis
      of acute coronary syndromes, though the precise morphological mechanisms
      underlying this process remain unclear. CASE PRESENTATION: A 43-year-old man with
      a history of multivessel coronary vasospastic angina had been treated with long
      acting diltiazem and fluvastatin since 2004. Eleven years later, following 1
      month of medication nonadherence, he experienced recurrence of rest angina and
      myocardial infarction, with elevated high-sensitivity troponin T. An emergency
      coronary angiogram demonstrated no de novo lesions, and the current episode was
      diagnosed as intractable sustained coronary spasm-induced anterior myocardial
      infarction. Optical coherence tomography imaging revealed the coronary plaque
      with homogeneous high-intensity signal, and a clearly visualized intraplaque
      neovascular microchannel (NVMC) network. CONCLUSIONS: Neovascularization within a
      coronary atheroma is known to accelerate coronary atherosclerosis. The current
      case with coronary vasospastic angina highlights the role of NVMC formation in
      this process.

PMID- 27884128
TI  - A randomised controlled demonstration trial of multifaceted nutritional
      intervention and or probiotics: the healthy mums and babies (HUMBA) trial.
AB  - BACKGROUND: Maternal obesity is associated with adverse pregnancy outcomes and
      has lifelong negative implications for offspring health. The Institute of
      Medicine recommends limited gestational weight gain (GWG) in obese women for
      optimal maternal and infant outcomes. However, there is a gap regarding an
      effective and sustainable intervention strategy to achieve this goal. The aim of
      the healthy mums and babies (HUMBA) demonstration trial is to assess whether a
      multifaceted nutritional intervention and/or an oral probiotic treatment in obese
      pregnant women can reduce excessive GWG and optimise pregnancy outcomes. METHODS
      AND DESIGN: The study is a two by two factorial randomised controlled
      demonstration trial conducted in Counties Manukau health region, New Zealand, a
      multi-ethnic region with a high prevalence of obesity. A total of 220 non
      diabetic obese women with a singleton pregnancy will be recruited between 120 and
      176 weeks. At recruitment, women are randomised to receive either a culturally
      tailored multifaceted dietary intervention or routine dietary advice, and either
      an oral probiotic or placebo capsule. Randomisation is undertaken via a web-based
      protocol, randomize.net, with a 1:1 ratio using stratification by body mass index
      (BMI) category (BMI of 30-34.9 or BMI >=35 kg/m2). The dietary intervention
      includes 4 customised nutrition education visits by a trained community health
      worker combined with motivational text messaging. Probiotic capsules consist of
      Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 at a dose of 7 * 109
      colony-forming units one per day until birth. Probiotic and placebo capsules are
      identically pre-packed and labelled by a third party, and are prescribed in a
      double blinded fashion. Research assessments are conducted at enrolment, 28
      weeks, 36 weeks, at birth and at 5 months post-delivery. The primary outcomes for
      the study are proportion of women with excessive GWG and infant birthweight.
      DISCUSSION: The HUMBA demonstration trial will assess the efficacy of a
      culturally tailored multifaceted dietary intervention and probiotic treatment in
      limiting excessive GWG and optimising birthweight in a multiethnic sample of
      obese pregnant women. If successful, either one or both of the interventions may
      be incorporated into future studies powered to investigate important pregnancy
      outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      registration number: ACTRN12615000400561 , Universal Trial Number: U1111-1155
      0409. Date registered: 29th April 2015.

PMID- 27884130
TI  - A profile of The Clinical Course of Cognition and Comorbidity in Mild Cognitive
      Impairment and Dementia Study (The 4C study): two complementary longitudinal,
      clinical cohorts in the Netherlands.
AB  - BACKGROUND: Heterogeneous disease trajectories of mild cognitive impairment (MCI)
      and dementia are frequently encountered in clinical practice, but there is still
      insufficient knowledge to understand the reasons and mechanisms causing this
      heterogeneity. In addition to correlates of the disorder, patient characteristics
      such as their health status, social environment, comorbidities and frailty may
      contribute to variability in trajectories over time. The current paper outlines
      the study design and the study population of and provides an overview of the data
      collected in the Clinical Course of Cognition and Comorbidity in Mild Cognitive
      Impairment (4C-MCI cohort, n = 315) and Dementia (4C-Dementia cohort, n = 331)
      Study. METHODS: The two complementary longitudinal cohorts part of the 4C study
      began enrolment in March 2010. Participants were prospectively recruited from
      three collaborating Dutch Alzheimer Centers, with three annual follow-up
      assessments after baseline. Extensive neuropsychological assessments, and
      detailed profiling of comorbidities, health and frailty at each follow up were
      the key features of the 4C study. As such, the 4C study was designed to study if
      and how patients' comorbidities and frailty are associated with the course of MCI
      and dementia measured with a comprehensive and multidimensional set of outcomes
      including cognition, daily functioning, quality of life, behavioral disturbances,
      caregiver burden, institutionalization and death and whether the effects of
      medical health and frailty differ between MCI and dementia stages of cognitive
      disorders. CONCLUSION: Sampled in a clinical setting, the 4C study complements
      population-based studies on neurodegenerative disorders in terms of the type of
      assessment (e.g. comorbidity, frailty, and functional status were repeatedly
      assessed). The 4C study complements available clinical cohorts of MCI and
      dementia patients, because the exclusion criteria were kept to a minimum, to
      obtain a sample that is representative for the average patient visiting a memory
      clinic.

PMID- 27884131
TI  - Improvement of pressure ulcer prevention care in private for-profit residential
      care homes: an action research study.
AB  - BACKGROUND: A need exits to develop a protocol for preventing pressure ulcers
      (PUs) in private for-profit nursing homes in Hong Kong, where the incidence of
      PUs is relatively high and which have high proportion of non-professional care
      staff. The implementation of such protocol would involve changes in the practice
      of care, likely evoking feelings of fear and uncertainty that may become a
      barrier to staff adherence. We thus adopted the Systems Model of Action Research
      in this study to manage the process of change for improving PU prevention care
      and to develop a pressure ulcer prevention protocol for private for-profit
      nursing homes. METHODS: A total of 474 residents and care staff who were health
      workers, personal care workers, and/or nurses from four private, for-profit
      nursing homes in Hong Kong participated in this study. Three cyclic stages and
      steps, namely, unfreezing (planning), changing (action), and refreezing (results)
      were carried out. During each cycle, focus group interviews, field observations
      of the care staff's practices and inspections of the skin of the residents for
      pressure ulcers were conducted to evaluate the implementation of the protocol.
      Qualitative content analysis was adopted to analyse the data. The data and
      methodological triangulation used in this study increased the credibility and
      validity of the results. RESULTS: The following nine themes emerged from this
      study: prevention practices after the occurrence of PUs, the improper use of
      pressure ulcer prevention materials, non-compliance with several prevention
      practices, improper prevention practices, the perception that the preventive care
      was being performed correctly, inadequate readiness to use the risk assessment
      tool, an undesirable environment, the supplying of unfavorable resources, and
      various management styles in the homes with or without nurses. At the end of the
      third cycle, the changes that were identified included improved compliance with
      the revised risk assessment method, the timely and appropriate use of PU
      prevention materials, the empowering of staff to improve the quality of PU care,
      and improved home management. CONCLUSION: Through the action research approach,
      the care staff were empowered and their PU prevention care practices had
      improved, which contributed to the decreased incidence of pressure ulcers. A PU
      prevention protocol that was accepted by the staff was finally developed as the
      standard of care for such homes.

PMID- 27884132
TI  - Healthy and productive workers: using intervention mapping to design a workplace
      health promotion and wellness program to improve presenteeism.
AB  - BACKGROUND: Presenteeism is a growing problem in developed countries mostly due
      to an aging workforce. The economic costs related to presenteeism exceed those of
      absenteeism and employer health costs. Employers are implementing workplace
      health promotion and wellness programs to improve health among workers and reduce
      presenteeism. How best to design, integrate and deliver these programs are
      unknown. The main purpose of this study was to use an intervention mapping
      approach to develop a workplace health promotion and wellness program aimed at
      reducing presenteeism. METHODS: We partnered with a large international financial
      services company and used a qualitative synthesis based on an intervention
      mapping methodology. Evidence from systematic reviews and key articles on
      reducing presenteeism and implementing health promotion programs was combined
      with theoretical models for changing behavior and stakeholder experience. This
      was then systematically operationalized into a program using discussion groups
      and consensus among experts and stakeholders. RESULTS: The top health problem
      impacting our workplace partner was mental health. Depression and stress were the
      first and second highest cause of productivity loss respectively. A multi-pronged
      program with detailed action steps was developed and directed at key stakeholders
      and health conditions. For mental health, regular sharing focus groups, social
      networking, monthly personal stories from leadership using webinars and multi
      media communications, expert-led workshops, lunch and learn sessions and manager
      and employee training were part of a comprehensive program. Comprehensive,
      specific and multi-pronged strategies were developed and aimed at encouraging
      healthy behaviours that impact presenteeism such as regular exercise, proper
      nutrition, adequate sleep, smoking cessation, socialization and work-life
      balance. Limitations of the intervention mapping process included high resource
      and time requirements, the lack of external input and viewpoints skewed towards
      middle and upper management, and using secondary workplace data of unknown
      validity and reliability. CONCLUSIONS: In general, intervention mapping was a
      useful method to develop a workplace health promotion and wellness program aimed
      at reducing presenteeism. The methodology provided a step-by-step process to
      unravel a complex problem. The process compelled participants to think
      critically, collaboratively and in nontraditional ways.

PMID- 27884133
TI  - Recovering disrupted social capital: insights from Lao DPR rural villagers'
      perceptions of local leadership.
AB  - BACKGROUND: Social capital is often believed to be one of the key prerequisites
      for successful implementation of community-based health programs. In less
      developed countries, local leaders are positioned as major players in broad
      community health strategies and interventions, and their capacities and roles are
      expected to increase in prominence in future community-health-care promotions. In
      this study, we examined how local leaders' capacities could be related to social
      capital in rural villages in Lao PDR, and thus to villagers' willingness to
      participate in community-based health efforts. METHODS: We adopted a qualitative
      approach, conducting semi-structured interviews for both individuals and focus
      groups. In 2012, 103 people from six villages in the Khoun and Phoukoud districts
      participated in the interviews. For the individual interviews, we interviewed 22
      mothers who had given birth in the past 5 years. For the focus groups, we
      interviewed 30 women (six groups), 30 men (six groups), and 21 senior villagers
      (five groups). RESULTS: First, we noted large variations in the levels of
      community social capital across villages: four out of six study villages showed a
      high level of social capital, while two villages suffered greatly from a low
      level of social capital. In search of the reasons for the disrupted social
      capital in the latter two villages, interviews revealed that failed leadership,
      especially in regard to local resource allocations-lack of transparency and
      corrupt practices-were commonly cited reasons for disrupted social capital. The
      data also showed that the villagers' mistrust of these failed local leaders
      critically reduced their willingness to participate in community-based health
      efforts, and especially in those that involved resource mobilization and risk
      sharing for healthcare. Finally, we found that good communication skills and
      participatory decision-making styles were attributes that rural villagers in Lao
      PDR expected of their local leaders. CONCLUSION: This study suggests that failed
      local leadership is detrimental to community participation, resource
      mobilization, and building communities' social capital. To achieve intended
      health care goals through community-based interventions, there is a need to first
      support local leadership at all levels through capacity-building and improved
      communication within communities.

PMID- 27884135
TI  - Online platform for applying space-time scan statistics for prospectively
      detecting emerging hot spots of dengue fever.
AB  - BACKGROUND: Cases of dengue fever have increased in areas of Southeast Asia in
      recent years. Taiwan hit a record-high 42,856 cases in 2015, with the majority in
      southern Tainan and Kaohsiung Cities. Leveraging spatial statistics and geo
      visualization techniques, we aim to design an online analytical tool for local
      public health workers to prospectively identify ongoing hot spots of dengue fever
      weekly at the village level. METHODS: A total of 57,516 confirmed cases of dengue
      fever in 2014 and 2015 were obtained from the Taiwan Centers for Disease Control
      (TCDC). Incorporating demographic information as covariates with cumulative cases
      (365 days) in a discrete Poisson model, we iteratively applied space-time scan
      statistics by SaTScan software to detect the currently active cluster of dengue
      fever (reported as relative risk) in each village of Tainan and Kaohsiung every
      week. A village with a relative risk >1 and p value <0.05 was identified as a
      dengue-epidemic area. Assuming an ongoing transmission might continuously spread
      for two consecutive weeks, we estimated the sensitivity and specificity for
      detecting outbreaks by comparing the scan-based classification (dengue-epidemic
      vs. dengue-free village) with the true cumulative case numbers from the TCDC's
      surveillance statistics. RESULTS: Among the 1648 villages in Tainan and
      Kaohsiung, the overall sensitivity for detecting outbreaks increases as case
      numbers grow in a total of 92 weekly simulations. The specificity for detecting
      outbreaks behaves inversely, compared to the sensitivity. On average, the mean
      sensitivity and specificity of 2-week hot spot detection were 0.615 and 0.891
      respectively (p value <0.001) for the covariate adjustment model, as the maximum
      spatial and temporal windows were specified as 50% of the total population at
      risk and 28 days. Dengue-epidemic villages were visualized and explored in an
      interactive map. CONCLUSIONS: We designed an online analytical tool for front
      line public health workers to prospectively detect ongoing dengue fever
      transmission on a weekly basis at the village level by using the routine
      surveillance data.

PMID- 27884134
TI  - Treatment-emergent depression and anxiety between peginterferon alpha-2a versus
      alpha-2b plus ribavirin for chronic hepatitis C.
AB  - BACKGROUND: This study investigates differences in depression and anxiety between
      patients with chronic hepatitis C who are treated with peginterferon alpha-2a
      (PegIFN-alpha-2a) plus ribavirin and those who are treated with peginterferon
      alpha-2b (PegIFN-alpha-2b) plus ribavirin. METHODS: In this 24 week, non
      randomized, observational, prospective study, 55 patients with chronic hepatitis
      C were treated with PegIFN-alpha-2a plus ribavirin (Group 1), and 26 patients
      were treated with PegIFN-alpha-2b plus ribavirin (Group 2). All patients
      underwent assessment using the Hospital Anxiety and Depression Scale (HADS) at
      the baseline and at weeks 4, 12 and 24. Patients with depression scores (HADS-D)
      >= 8 and anxiety scores (HADS-A) >= 8 were defined as having depression and
      anxiety, respectively. The factors that were associated with depression and
      anxiety during the 24 week antiviral treatment were determined. RESULTS: During
      the 24 week antiviral treatment, the proportion of patients with depression
      significantly increased over time in both groups (Group 1: p = 0.048; Group 2: p
      = 0.044). The proportion of patients with anxiety did not significantly change
      during the follow-up period in either group. Incidences of depression or anxiety
      did not differ significantly between Group 1 and Group 2. A history of alcohol
      use disorder was an independent predictor of depression at week 12 (p < 0.001)
      and week 24 (p < 0.001), and a poor virological response to treatment was
      associated with depression at week 24 (p = 0.029). Patients who had more physical
      comorbidities were more likely to suffer from anxiety at week 12 (p = 0.038).
      CONCLUSIONS: This study did not identify significant differences in depression or
      anxiety between in patients with chronic hepatitis C who underwent a 24 week
      antiviral treatment regimen with PegIFN-alpha-2a plus ribavirin and those who
      underwent a regiment with PegIFN-alpha-2b plus ribavirin. Future research with
      larger samples and a randomized, controlled design are required to verify the
      findings in this study. TRIAL REGISTRATION: This clinical study has been
      registered at ClinicalTrials.gov. (Trial registration: NCT02943330 ).

PMID- 27884136
TI  - Erratum to: Prognostic impact of CXCL16 and CXCR6 in non-small cell lung cancer:
      combined high CXCL16 expression in tumor stroma and cancer cells yields improved
      survival.

PMID- 27884138
TI  - Household dietary diversity and Animal Source Food consumption in Ethiopia:
      evidence from the 2011 Welfare Monitoring Survey.
AB  - BACKGROUND: It is imperative to track dietary quality and progress in nutritional
      outcomes in a population to develop timely interventions. Dietary diversity is a
      commonly used proxy to assess dietary quality in low-income countries. This study
      identified predictors of household dietary diversity in Ethiopia and pattern of
      consumption of animal source food (ASF) among households. METHODS: Secondary data
      were analyzed from the 2011 Ethiopian Welfare Monitoring Survey (WMS). This
      survey used a structured questionnaire to collect socio-demographic and economic
      data. Dietary data were collected using a dietary diversity questionnaire
      measuring dietary diversity over the past 1 week. A Household Dietary Diversity
      Score (HDDS) was constructed according to the Food and Agricultural Organization
      (FAO) guidelines. Consumption of ASFs is described by its distribution among the
      regions and by HDDS. Multiple logistic regression analysis was fitted to identify
      independent predictors for HDDS. RESULTS: A total of 27,995 households were
      included in the analyses. A little over half of the study households (52.2%) had
      more than four household members, and 75% of households were male headed. The
      mean HHDS was five food groups. Cereals were the most commonly (96%) consumed
      food groups. Fish, egg and fruits, on the other hand, were the least consumed
      food groups. ASFs were consumed in greater proportion among households with
      higher HDDS. Being part of the higher and middle socio economic strata (P <
      0.001), literacy (P < 0.01), urban residence (P < 0.01), male headed household (P
      < 0.01), larger family size (P <0.01) and owning livestock (P < 0.01) were
      positively associated with higher HDDS. CONCLUSIONS: Considering these findings,
      nutrition sensitive interventions which address the problem through economic and
      educational empowerment and modern technologies supporting agricultural practices
      need to be designed to increase both local production and increased consumption.

PMID- 27884137
TI  - Early identification in primary health care of people at risk for sick leave due
      to work-related stress - study protocol of a randomized controlled trial (RCT).
AB  - BACKGROUND: Early identification of persons at risk of sickness absence due to
      work-related stress is a crucial problem for society in general, and primary
      health care in particular. Tho date, no established method to do this exists.
      This project's aim is to evaluate whether systematic early identification of work
      related stress can prevent sickness absence. This paper presents the study
      design, procedure and outcome measurements, as well as allocation and baseline
      characteristics of the study population. METHOD/DESIGN: The study is a two-armed
      randomized controlled trial with follow-up at 3, 6 and 12 months. Non-sick-listed
      employed women and men, aged 18 to 64 years, who had mental and physical health
      complaints and sought care at primary health care centers (PHCC) were eligible to
      participate. At baseline work-related stress was measured by the Work Stress
      Questionnaire (WSQ), combined with feedback at consultation, at PHCC. The
      preventive intervention included early identification of work-related stress by
      the WSQ, GP training in the use of WSQ, GP feedback at consultation and finding
      suitable preventive measures. A process evaluation was used to explore how to
      facilitate future implementation and structural use of the WSQ at the PHCC. The
      primary outcome to compare the preventive sick leave intervention by the general
      practitioner (GP) versus treatment as usual is sick leave data obtained from the
      Swedish Social Insurance Agency register. DISCUSSION: Early screening for sick
      leave due to work-related stress makes it possible not only to identify those at
      risk for sick leave, but also to put focus on the patient's specific work-related
      stress problems, which can be helpful in finding suitable preventive measures.
      This study investigates if use of the WSQ by GPs at PHCCs, combined with feedback
      at consultation, prevents future sickness absence. TRIAL REGISTRATION:
      ClinicalTrials.gov. Identifier: NCT02480855 . Registered 20 May 2015.

PMID- 27884139
TI  - Brominated flame retardants in placental tissues: associations with infant sex
      and thyroid hormone endpoints.
AB  - BACKGROUND: Brominated flame retardants (BFRs) are endocrine disruptors that
      bioaccumulate in the placenta, but it remains unclear if they disrupt tissue
      thyroid hormone (TH) metabolism. Our primary goal was to investigate associations
      between placental BFRs, TH levels, Type 3 deiodinase (DIO3) activity and TH
      sulfotransferase (SULT) activities. METHODS: Placenta samples collected from 95
      women who delivered term (>37 weeks) infants in Durham, NC, USA (enrolled 2010
      2011) were analyzed for polybrominated diphenyl ethers (PBDEs), 2,4,6
      tribromophenol (2,4,6-TBP), THs (T4, T3 and rT3), and DIO3 and TH SULT
      activities. RESULTS: PBDEs and 2,4,6-TBP were detected in all placenta samples.
      PBDEs were higher in placental tissues from male infants compared to female
      infants, with 2,4,6-TBP and BDE-209 levels approximately twice as high. Among
      male infants, placental BDE-99 and BDE-209 were negatively associated with rT3
      placental levels. For female infants, placental BDE-99 and 2,4,6-TBP were
      positively associated with T3 concentrations. DIO3 activity was also
      significantly higher in placental tissues from male infants compared to females,
      while 3,3'-T2 SULT activity was significantly higher in placental tissues from
      females compared to males. Among males, several PBDE congeners were positively
      correlated with T3 SULT, while BDE-99 was negatively associated with T3 SULT
      among females. Associations generally remained after adjustment for potential
      confounding by maternal age and gestational age at delivery. CONCLUSIONS: These
      results suggest BFRs accumulate in the placenta and potentially alter TH function
      in a sex-specific manner, a possible mechanism to explain the sex-dependent
      impacts of environmental exposure on children's growth and development. More
      research is needed to elucidate the effects of BFRs on placenta function during
      pregnancy, as well as the biological consequences of exposure and thyroid
      disruption.

PMID- 27884141
TI  - Normal patellofemoral kinematic patterns during daily activities in dogs.
AB  - BACKGROUND: Patellar abnormalities are a common cause of pain and lameness in
      dogs; however, in vivo the relative motion between the femur and patella in dogs
      is not well described. The objective of this study was to define normal in vivo
      sagittal plane patellofemoral kinematics in three axes of motion using non
      invasive methods. We hypothesized patellofemoral alignment in the sagittal plane
      would tightly correlate with the femorotibial flexion angle. Six healthy dogs
      without orthopedic disease underwent computed tomography (CT) of their hind limbs
      to create 3-D models of the patella and femur. Normal stifle joint motion was
      captured via flat-panel imaging while each dog performed a series of routine
      activities, including sitting, walking, and trotting. The 3-D models of the
      patella and femur were digitally superimposed over the radiographic images with
      shape-matching software and the precise movement of the patella relative to the
      femur was calculated. RESULTS: As the femorotibial joint flexed, the
      patellofemoral joint also flexed and the patella moved caudally and distally
      within the femoral trochlea during each activity. Patellar flexion and distal
      translation during walk and sit were linearly coupled with the femorotibial
      flexion angle. Offset was evident while trotting, where patella poses were
      significantly different between early and late swing phase (p <= 0.003). Patellar
      flexion ranged from 51 to 6 degrees  while trotting. The largest flexion angle
      (92 degrees ) occurred during sit. The patella traversed the entire proximodistal
      length of the femoral trochlea during these daily activities. CONCLUSIONS: Using
      single-plane flat-panel imaging, we demonstrated normal in vivo patellofemoral
      kinematics is tightly coupled with femorotibial kinematics; however, trot
      kinematic patterns did not follow the path defined by walking and stand-to-sit
      motions. Our normal data can be used in future studies to help define
      patellofemoral joint kinematics in dogs with stifle abnormalities.

PMID- 27884140
TI  - Phase II clinical study of valproic acid plus cisplatin and cetuximab in
      recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE
      trial.
AB  - BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck
      (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with
      or without 5-fluorouracil, is the gold standard treatment in this stage. Thus,
      the concomitant use of novel compounds represents a critical strategy to improve
      treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of
      several anticancer drugs including cisplatin and anti-Epidermal Growth Factor
      Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that
      vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR)
      expression and to revert epithelial to mesenchimal transition (EMT). Due to its
      histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic
      therapy for epileptic disorders, valproic acid (VPA) has been considered a good
      candidate for anticancer therapy. A reasonable option may be to employ the
      combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking
      advantage of the possible positive interaction between histone deacetylase
      inhibitors, cisplatin and/or anti-EGFR. METHOD/DESIGN: V-CHANCE is a phase 2
      clinical trial evaluating, in patients with recurrent/metastatic squamous cell
      carcinoma of the head and neck never treated with first-line chemotherapy, the
      concomitant standard administration of cisplatin (on day 1, every 3 weeks) and
      cetuximab (on day 1, weekly), in combination with oral VPA given daily from day 
      14 with a titration strategy in each patient (target serum level of 50-100
      MUg/ml). Primary end point is the objective response rate measured according to
      Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated
      according to Simon 2 stage minimax design will include 21 patients in the first
      stage with upper limit for rejection being 8 responses, and 39 patients in the
      second stage, with upper limit for rejection being 18 responses. Secondary
      endpoints are time to progression, duration of response, overall survival,
      safety. Objectives of the translational study are the evaluation on tumor samples
      of markers of treatment efficacy/resistance (i.e. gammaH2AX, p21/WAF, RAD51,
      XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity
      (histones and proteins acetylation, Histone deacetylase isoforms) as well as
      valproate test, histones and proteins acetylation of peripheral blood mononuclear
      cell, tested on blood samples at baseline and at different time points during
      treatment. DISCUSSION: Overall, this study could provide a less toxic and more
      effective first-line chemotherapy regimen in patients with recurrent/metastatic
      squamous cell carcinoma of the head and neck by demonstrating the feasibility and
      efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies
      could help to identify responder patients, and will add insights in the mechanism
      of the synergistic interaction between these agents. EUDRACT NUMBER: 2014-001523
      69 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02624128.

PMID- 27884143
TI  - The using of a piglets as a model for evaluating the dipyrone hematological
      effects.
AB  - BACKGROUND: Dipyrone (MET, metamizole) is a non-steroidal anti-inflammatory drug
      commonly used both in human and in veterinary medicine. After oral
      administration, is broken down rapidly to metabolites which largely retain the
      activity of the parent drug. Its metabolites have analgesic, antipyretic and anti
      inflammatory effects. RESULTS: The subjects were eight healthy male Large White
      post-suckling piglets, weighing between 5.0 to 7.4 kg, of ages 35 +/- 10 days.
      The animals were administered MET (100 mg/kg) by an intramuscular (I.M.)
      injection. The study calculated the value of several hemorheological parameters.
      Significant impact of MET treatment (p < 0.05) was proven in case: activated
      partial thromboplastin time; ratio of activated partial thromboplastin time;
      hemoglobin; hematocrit; mean corpuscular hemoglobin; mean corpuscular volume; red
      blood cells volume; white blood cells volume; prothrombin time index.
      CONCLUSIONS: In summation, our observations suggest that a piglet model is useful
      for studying the impact of MET on hemorheological parameters.

PMID- 27884142
TI  - DNA methylation patterns associated with oxidative stress in an ageing
      population.
AB  - BACKGROUND: Oxidative stress has been related to type 2 diabetes (T2D) and
      cardiovascular disease (CVD), the leading global cause of death. Contributions of
      environmental factors such as oxidative stress on complex traits and disease may
      be partly mediated through changes in epigenetic marks (e.g. DNA methylation).
      Studies relating differential methylation with intermediate phenotypes and
      disease endpoints may be useful in identifying additional candidate genes and
      mechanisms involved in disease. METHODS: To investigate the role of epigenetic
      variation in oxidative stress marker levels and subsequent development of CVD and
      T2D, we performed analyses of genome-wide DNA methylation in blood, ten markers
      of oxidative stress (total glutathione [TGSH], reduced glutathione [GSH],
      oxidised glutathione [GSSG], GSSG to GSH ratio, homocysteine [HCY], oxidised low
      density lipoprotein (oxLDL), antibodies against oxLDL [OLAB], conjugated dienes
      [CD], baseline conjugated dienes [BCD]-LDL and total antioxidant capacity [TAOC])
      and incident disease in up to 966 age-matched individuals. RESULTS: In total, we
      found 66 cytosine-guanine (CpG) sites associated with one or more oxidative
      stress markers (false discovery rate [FDR] <0.05). These sites were enriched in
      regulatory regions of the genome. Genes annotated to CpG sites showed enrichment
      in annotation clusters relating to phospho-metabolism and proteins with
      pleckstrin domains. We investigated the contribution of oxidative stress
      associated CpGs to development of cardiometabolic disease. Methylation variation
      at CpGs in the 3'-UTR of HIST1H4D (cg08170869; histone cluster 1, H4d) and in the
      body of DVL1 (cg03465880; dishevelled-1) were associated with incident T2D events
      during 10 years of follow-up (all permutation p-values <0.01), indicating a role
      of epigenetic regulation in oxidative stress processes leading to development or
      progression of diabetes. Methylation QTL (meQTL) analysis showed significant
      associations with genetic sequence variants in cis at 28 (42%) of oxidative
      stress phenotype-associated sites (FDR < 0.05). Integrating cis-meQTLs with
      genotype-phenotype associations indicated that genetic effects on oxidative
      stress phenotype at one locus (cg07547695; BCL2L11) may be mediated through DNA
      methylation. CONCLUSIONS: In conclusion, we report novel associations of DNA
      methylation with oxidative stress, some of which also show evidence of a relation
      with T2D incidence.

PMID- 27884144
TI  - Assessment of serology and spirometry and the combination of both to complement
      microbiological isolation for earlier detection of Pseudomonas aeruginosa
      infection in children with cystic fibrosis.
AB  - BACKGROUND: The aim of this study was to assess whether serology and spirometry
      and the combination of both can complement culture-based detection for earlier
      recognition of Pseudomonas aeruginosa infection in children with cystic fibrosis.
      METHODS: A 4 year longitudinal prospective study that included 67 Slovenian
      children with cystic fibrosis with a mean age of 10.5 years was conducted.
      Serology, spirometry and a scoring system combining serology and spirometry were
      assessed and compared. Infection was confirmed with isolation of Pseudomonas
      aeruginosa from respiratory samples. RESULTS: There was a significantly positive
      correlation between serology and the combination of serology and spirometry and
      Pseudomonas aeruginosa isolation (P < 0.01 for both) and a significantly negative
      correlation between spirometry and Pseudomonas aeruginosa isolation (P < 0.05).
      An increase in serology for 1 ELISA unit increased the possibility of Pseudomonas
      aeruginosa isolation 1.6 times. A fall in FEV1% predicted for 10% increased the
      possibility of Pseudomonas aeruginosa isolation 9.8 times. Binary logistic
      regression analysis was used to determine the odds ratios and 95% confidence
      intervals for all three approaches. Serology had the highest specificity (0.80)
      and the combination of serology and spirometry the highest sensitivity (0.90).
      Both had a high negative predictive value (0.93 and 0.79 respectively).
      CONCLUSION: Using serology and the combination of serology and lung function
      measurement can be beneficial for earlier detection of infection with Pseudomonas
      aeruginosa in children with cystic fibrosis when done simultaneously with
      standard culture-based detection from respiratory samples.

PMID- 27884145
TI  - Estimation of the cool executive function using frontal electroencephalogram
      signals in first-episode schizophrenia patients.
AB  - BACKGROUND: In schizophrenia, executive dysfunction is the most critical
      cognitive impairment, and is associated with abnormal neural activities,
      especially in the frontal lobes. Complexity estimation using electroencephalogram
      (EEG) recording based on nonlinear dynamics and task performance tests have been
      widely used to estimate executive dysfunction in schizophrenia. METHODS: The
      present study estimated the cool executive function based on fractal dimension
      (FD) values of EEG data recorded from first-episode schizophrenia patients and
      healthy controls during the performance of three cool executive function tasks,
      namely, the Trail Making Test-A (TMT-A), Trail Making Test-B (TMT-B), and Tower
      of Hanoi tasks. RESULTS: The results show that the complexity of the frontal EEG
      signals that were measured using FD was different in first-episode schizophrenia
      patients during the manipulation of executive function. However, no differences
      between patients and controls were found in the FD values of the EEG data that
      was recorded during the performance of the Tower of Hanoi task. CONCLUSIONS:
      These results suggest that cool executive function exhibits little impairment in
      first-episode schizophrenia patients.

PMID- 27884148
TI  - A framework: make it useful to guide and improve practice of clinical trial
      design in smaller populations.
AB  - The increased attention to design and analysis of randomised clinical trials in
      small populations has triggered thinking regarding the most appropriate design
      methods for a particular clinical research question. Decision schemes and
      algorithms have been proposed, with varying starting points and foci. Parmar et
      al. (BMC Medicine 14:183, 2016) proposed a framework designed to assist the
      clinical trial team in design choices during protocol preparation. Herein,
      further stimulus is given regarding the extent to which a framework may help
      change practice for the better, the careful considerations for changing the usual
      error levels applied and the room for innovation in clinical trial design.Please
      see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916
      016-0722-3 .

PMID- 27884146
TI  - Demographic and clinical profiles of Plasmodium falciparum and Plasmodium vivax
      patients at a tertiary care centre in southwestern India.
AB  - BACKGROUND: Malaria remains an important cause of morbidity and mortality in
      India. Though many comprehensive studies have been carried out in Africa and
      Southeast Asia to characterize and examine determinants of Plasmodium falciparum
      and Plasmodium vivax malaria pathogenesis, fewer have been conducted in India.
      METHODS: A prospective study of malaria-positive individuals was conducted at Goa
      Medical College and Hospital (GMC) from 2012 to 2015 to identify demographic,
      diagnostic and clinical indicators associated with P. falciparum and P. vivax
      infection on univariate analysis. RESULTS: Between 2012 and 2015, 74,571 febrile
      individuals, 6287 (8.4%) of whom were malaria positive, presented to GMC. The
      total number of malaria cases at GMC increased more than two-fold over four
      years, with both P. vivax and P. falciparum cases present year-round. Some 1116
      malaria-positive individuals (mean age = 27, 91% male), 88.2% of whom were born
      outside of Goa and 51% of whom were construction workers, were enroled in the
      study. Of 1088 confirmed malaria-positive patients, 77.0% had P. vivax, 21.0% had
      P. falciparum and 2.0% had mixed malaria. Patients over 40 years of age and with
      P. falciparum infection were significantly (p < 0.001) more likely to be
      hospitalised than younger and P. vivax patients, respectively. While
      approximately equal percentages of hospitalised P. falciparum (76.6%) and P.
      vivax (78.9%) cases presented with at least one WHO severity indicator, a greater
      percentage of P. falciparum inpatients presented with at least two (43.9%, p <
      0.05) and at least three (29.9%, p < 0.01) severity features. There were six
      deaths among the 182 hospitalised malaria positive patients, all of whom had P.
      falciparum. CONCLUSION: During the four year study period at GMC, the number of
      malaria cases increased substantially and the greatest burden of severe disease
      was contributed by P. falciparum.

PMID- 27884147
TI  - Effects of osteopathic treatment on pulmonary function and chronic thoracic pain
      after coronary artery bypass graft surgery (OstinCaRe): study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: Coronary artery bypass graft surgery (CABG) is an effective and
      widespread coronary revascularisation technique, nevertheless there are a number
      of long-term postoperative complications from which patients can suffer. One year
      after CABG surgery pulmonary function is decreased by 12% and 30% of the patients
      suffer from chronic thoracic pain. To date and to our knowledge there are no
      effective treatments for these conditions. The aim of the present clinical trial
      is to explore the effectiveness of osteopathic treatment on these conditions.
      METHODS: The study is designed as a randomised controlled trial with two parallel
      groups. Group A will receive a standard cardiac rehabilitation programme during
      12 weeks and group B will receive the same standard cardiac rehabilitation
      programme supplemented with four osteopathic treatments (OT). OT will be
      performed at week 4, 5, 8 and 12 after surgery. Three hundred and eight patients
      (Group A: n = 154, Group B: n = 154) will be enrolled from the cardiothoracic
      surgery department of the Jessa Hospital Hasselt. Blinding will be assured for
      the staff of the cardiac rehabilitation centre and outcome assessors. Primary
      outcome measure will be the mean difference in change from baseline in slow vital
      capacity (SVC) at 12 weeks after surgery between groups. Secondary outcome
      measures will be the change from baseline in quality of life, pain, thoracic
      stiffness and maximal aerobic capacity at 12 weeks after surgery. A follow-up is
      planned 52 weeks after surgery for SVC, quality of life, pain and thoracic
      stiffness. Intention to treat analysis will be executed. DISCUSSION: The
      OstinCare study has been designed to explore the potential long-term added value
      of osteopathic treatment in the management of decreased pulmonary function,
      chronic thoracic pain and diminished thoracic mobility after CABG surgery. TRIAL
      REGISTRATION: The protocol has been retrospectively registered on
      ClinicalTrials.gov ( NCT01714791 ).

PMID- 27884149
TI  - Sasa quelpaertensis leaf extract regulates microbial dysbiosis by modulating the
      composition and diversity of the microbiota in dextran sulfate sodium-induced
      colitis mice.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) are related to a dysfunction of the
      mucosal immune system and they result from complex interactions between genetics
      and environmental factors, including lifestyle, diet, and the gut microbiome.
      Therefore, the effect of Sasa quelpaertensis leaf extract (SQE) on gut microbiota
      in a dextran sulfate sodium (DSS)-induced colitis mouse model was investigated
      with pyrosequencing of fecal samples. METHODS: Three groups of animals were
      examined: i) a control group, ii) a group that was received 2.5% DSS in their
      drinking water for 7 days, followed by 7 days of untreated water, and then
      another 7 days of 2.5% DSS in their drinking water, and iii) a group that was
      presupplemented with SQE (300 mg/kg body weight) by gavage for two weeks prior to
      the same DSS treatment schedule described in ii. RESULTS: SQE supplementation
      alleviated disease activity scores and shortened colon length compared to the
      other two groups. In the DSS group, the proportion of Bacteroidetes increased,
      whereas that the proportion of Firmicutes was decreased compared to the control
      group. SQE supplementation recovered the proportions of Firmicutes and
      Bacteroidetes back to control levels. Moreover, the diversity of microbiota in
      the SQE supplementation group higher than that of the DSS group. CONCLUSION: SQE
      was found to protect mice from microbial dysbiosis associated with colitis by
      modulating the microbial composition and diversity of the microbiota present.
      These results provide valuable insight into microbiota-food component
      interactions in IBD.

PMID- 27884150
TI  - Identifying and prioritizing lower value services from Dutch specialist
      guidelines and a comparison with the UK do-not-do list.
AB  - BACKGROUND: The term 'lower value services' concerns healthcare that is of little
      or no value to the patient and consequently should not be provided routinely, or
      not be provided at all. De-adoption of lower value care may occur through
      explicit recommendations in clinical guidelines. The present study aimed to
      generate a comprehensive list of lower value services for the Netherlands that
      assesses the type of care and associated medical conditions. The list was
      compared with the NICE do-not-do list (United Kingdom). Finally, the feasibility
      of prioritizing the list was studied to identify conditions where de-adoption is
      warranted. METHODS: Dutch clinical guidelines (published from 2010 to 2015) were
      searched for lower value services. The lower value services identified were
      categorized by type of care (diagnostics, treatment with and without medication),
      type of lower value service (not routinely provided or not provided at all), and
      ICD10 codes (international classification of diseases). The list was prioritized
      per ICD10 code, based on the number of lower value services per ICD10 code,
      prevalence, and burden of disease. RESULTS: A total of 1366 lower value services
      were found in the 193 Dutch guidelines included in our study. Of the lower value
      services, 30% covered diagnostics, 29% related to surgical and medical treatment
      without drugs primarily, and 39% related to drug treatment. The majority (77%) of
      all lower value services was on care that should not be offered at all, whereas
      the other 23% recommended on care that should not be offered routinely. ICD10
      chapters that included most lower value services were neoplasms and diseases of
      the nervous system. Dutch guidelines appear to contain more lower value services
      than UK guidelines. The prioritization processes revealed several conditions,
      including back pain, chronic obstructive pulmonary disease, and ischemic heart
      diseases, where lower value services most likely occur and de-adoption is
      warranted. CONCLUSIONS: In this study, a comprehensive list of lower value
      services for Dutch hospital care was developed. A feasible method for
      prioritizing lower value services was established. Identifying and prioritizing
      lower value services is the first of several necessary steps in reducing them.

PMID- 27884151
TI  - Unearthing the transition rates between photoreceptor conformers.
AB  - BACKGROUND: Obtaining accurate estimates of biological or enzymatic reaction
      rates is critical in understanding the design principles of a network and how
      biological processes can be experimentally manipulated on demand. In many cases
      experimental limitations mean that some enzymatic rates cannot be measured
      directly, requiring mathematical algorithms to estimate them. Here, we describe a
      methodology that calculates rates at which light-regulated proteins switch
      between conformational states. We focus our analysis on the phytochrome family of
      photoreceptors found in cyanobacteria, plants and many optogenetic tools.
      Phytochrome proteins change between active (P A ) and inactive (P I ) states at
      rates that are proportional to photoconversion cross-sections and influenced by
      light quality, light intensity, thermal reactions and dimerisation. This work
      presents a method that can accurately calculate these photoconversion cross
      sections in the presence of multiple non-light regulated reactions. RESULTS: Our
      approach to calculating the photoconversion cross-sections comprises three steps:
      i) calculate the thermal reversion reaction rate(s); ii) develop search spaces
      from which all possible sets of photoconversion cross-sections exist, and; iii)
      estimate extinction coefficients that describe our absorption spectra. We confirm
      that the presented approach yields accurate results through the use of simulated
      test cases. Our test cases were further expanded to more realistic scenarios
      where noise, multiple thermal reactions and dimerisation are considered. Finally,
      we present the photoconversion cross-sections of an Arabidopsis phyB N-terminal
      fragment commonly used in optogenetic tools. CONCLUSIONS: The calculation of
      photoconversion cross-sections has implications for both photoreceptor and
      synthetic biologists. Our method allows, for the first time, direct comparisons
      of photoconversion cross-sections and response speeds of photoreceptors in
      different cellular environments and synthetic tools. Due to the generality of our
      procedure, as shown by the application to multiple test cases, the
      photoconversion cross-sections and quantum yields of any photoreceptor might now,
      in principle, be obtained.

PMID- 27884152
TI  - Use of self-gated radial cardiovascular magnetic resonance to detect and classify
      arrhythmias (atrial fibrillation and premature ventricular contraction).
AB  - BACKGROUND: Arrhythmia can significantly alter the image quality of
      cardiovascular magnetic resonance (CMR); automatic detection and sorting of the
      most frequent types of arrhythmias during the CMR acquisition could potentially
      improve image quality. New CMR techniques, such as non-Cartesian CMR, can allow
      self-gating: from cardiac motion-related signal changes, we can detect cardiac
      cycles without an electrocardiogram. We can further use this data to obtain a
      surrogate for RR intervals (valley intervals: VV). Our purpose was to evaluate
      the feasibility of an automated method for classification of non-arrhythmic (NA)
      (regular cycles) and arrhythmic patients (A) (irregular cycles), and for sorting
      of common arrhythmia patterns between atrial fibrillation (AF) and premature
      ventricular contraction (PVC), using the cardiac motion-related signal obtained
      during self-gated free-breathing radial cardiac cine CMR with compressed sensing
      reconstruction (XD-GRASP). METHODS: One hundred eleven patients underwent cardiac
      XD-GRASP CMR between October 2015 and February 2016; 33 were included for
      retrospective analysis with the proposed method (6 AF, 8 PVC, 19 NA; by recent
      ECG). We analyzed the VV, using pooled statistics (histograms) and sequential
      analysis (Poincare plots), including the median (medVV), the weighted mean
      (meanVV), the total number of VV values (VVval), and the total range (VVTR) and
      half range (VVHR) of the cumulative frequency distribution of VV, including the
      median to half range (medVV/VVHR) and the half range to total range (VVHR/VVTR)
      ratios. We designed a simple algorithm for using the VV results to differentiate
      A from NA, and AF from PVC. RESULTS: Between NA and A, meanVV, VVval, VVTR, VVHR,
      medVV/VVHR and VVHR/VVTR ratios were significantly different (p values = 0.00014,
      0.0027, 0.000028, 5*10-9, 0.002, respectively). Between AF and PVC, meanVV, VVval
      and medVV/VVHR ratio were significantly different (p values = 0.018, 0.007,
      0.044, respectively). Using our algorithm, sensitivity, specificity, and accuracy
      were 93 %, 95 % and 94 % to discriminate between NA and A, and 83 %, 71 %, and 77
      % to discriminate between AF and PVC, respectively; areas under the ROC curve
      were 0.93 and 0.89. CONCLUSIONS: Our study shows we can reliably detect
      arrhythmias and differentiate AF from PVC, using self-gated cardiac cine XD-GRASP
      CMR.

PMID- 27884153
TI  - Performance evaluation of the touchscreen-based MuseTM Auto CD4/CD4% single
      platform system for CD4 T cell numeration in absolute number and in percentage
      using blood samples from children and adult patients living in the Central
      African Republic.
AB  - BACKGROUND: The new microcapillary and fluorescence-based EC IVD-qualified MuseTM
      Auto CD4/CD4% single-platform assay (EMD Millipore Corporation, Merck Life
      Sciences, KGaA, Darmstadt, Germany) for CD4 T cell numeration in absolute number
      and in percentage was evaluated using Central African patients' samples compared
      against the reference EC IVD-qualified BD FACSCount (Becton-Dickinson, USA) flow
      cytometer. METHODS: EDTA-blood samples from 124 adults, 10 adolescents, 13
      children and 3 infants were tested in parallel at 2 reference laboratories in
      Bangui. RESULTS: The MuseTM technique was highly reproducible, with low intra-
      and inter-run variabilities less than 15%. CD4 T cell counts of MuseTM and BD
      FACSCount in absolute number and percentage were highly correlated (r2 = 0.99 and
      0.98, respectively). The mean absolute bias between MuseTM and BD FACSCount cells
      in absolute number and percentage were -5.91 cells/ul (95% CI -20.90 to 9.08)
      with limits of agreement from -77.50 to 202.40 cells/ul, and +1.69 %CD4 (95% CI
      +/-1.29 to +2.09), respectively. The percentages of outliers outside the limits
      of agreement were nearly similar in absolute number (8%) and percentage (10%).
      CD4 T cell counting by MuseTM allowed identifying the majority of individuals
      with CD4 T cell <200, <350 or <750 cells/ul corresponding to the relevant
      thresholds of therapeutic care, with sensitivities of 95.5-100% and specificities
      of 83.9-100%. CONCLUSIONS: The MuseTM Auto CD4/CD4% Assay analyzer is a reliable
      alternative flow cytometer for CD4 T lymphocyte enumeration to be used in routine
      immunological monitoring according to World Health Organization recommendations
      in HIV-infected adults as well as children living in resource-constrained
      settings.

PMID- 27884154
TI  - Isolation and characterization of adenoviruses infecting endangered golden snub
      nosed monkeys (Rhinopithecus roxellana).
AB  - BACKGROUND: Adenoviruses are important pathogens with the potential for
      interspecies transmission between humans and non-human primates. Although many
      adenoviruses have been identified in monkeys, the knowledge of these viruses from
      the Colobinae members is quite limited. FINDINGS: We conducted a surveillance of
      viral infection in endangered golden snub-nosed monkeys (Rhinopithecus roxellana)
      in the subfamily Colobinae in China, and found that 5.1% of sampled individuals
      were positive for adenovirus. One of the adenoviruses (SAdV-WIV19) was
      successfully isolated and its full-length genome was sequenced. The full-length
      genome of WIV19 is 33,562 bp in size, has a G + C content of 56.2%, and encodes
      35 putative genes. Sequence analysis revealed that this virus represents a novel
      species in the genus Mastadenovirus. Diverse cell lines, including those of human
      origin, were susceptible to WIV19. CONCLUSION: We report the first time the
      isolation and full-length genomic characterization of an adenovirus from the
      subfamily Colobinae.

PMID- 27884155
TI  - Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid
      (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2
      diabetes mellitus model (Stillman Salgado rats).
AB  - BACKGROUND: Diabetes mellitus (DM) is a complex disease with alterations in
      metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously
      develop type 2 DM by middle age showing progressive impairment of glucose
      tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We
      analyzed the effects of supplementation of omega-3 and omega-6 polyunsaturated
      fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an
      antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters
      in eSS rats to evaluate whether they can delay development and/or prevent
      progression of DM. METHODS: After weaning, eSS rats received, intraperitoneally,
      once a month omega-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or omega-6 (90% arachidonic
      acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9
      mg/kg NDGA added to omega-3 and omega-6 fatty acids. Blood samples were collected
      at day 40, and at the end of the 6th month and 12th month of age to determine
      plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin
      (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and
      hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas)
      and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats
      that received saline solution were used as controls. RESULTS: Plasma lipids
      profile, TG, fasting and post-prandial blood glucose levels, and glycosylated
      HbA1C showed significant improvements in omega-3 and omega-3 + NDGA treated
      animals compared to eSS control group. omega-3 and omega-3 + NDGA groups showed
      an inverse correlation with fasting blood glucose and showed lower plasma levels
      of GGT, TG, and CRP. eSS rats treated with omega-3 LCPUFAs showed reduced level
      of inflammatory and oxidative indices in plasma and liver, kidney and pancreas
      tissues in comparison with eSS control (non-treated) and omega-6 treated groups.
      CONCLUSIONS: eSS rats are a useful model to study type 2 DM pathophysiology and
      related inflammatory indices. omega-3 + NDGA supplementation, at the doses
      tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

PMID- 27884156
TI  - Targeted myocardial gene expression in failing hearts by RNA sequencing.
AB  - BACKGROUND: Myocardial recovery with left ventricular assist device (LVAD)
      therapy is highly variable and difficult to predict. Next generation ribonucleic
      acid (RNA) sequencing is an innovative, rapid, and quantitative approach to gene
      expression profiling in small amounts of tissue. Our primary goal was to identify
      baseline transcriptional profiles in non-ischemic cardiomyopathies that predict
      myocardial recovery in response to LVAD therapy. We also sought to verify
      transcriptional differences between failing and non-failing human hearts.
      METHODS: RNA was isolated from failing (n = 16) and non-failing (n = 8) human
      hearts. RNA from each patient was reverse transcribed and quantitatively
      sequenced on the personal genome machine (PGM) sequencer (Ion torrent) for 95
      heart failure candidate genes. Coverage analysis as well as mapping the reads and
      alignment was done using the Ion Torrent Browser SuiteTM. Differential expression
      analyses were conducted by empirical analysis of digital gene expression data in
      R (edgeR) to identify differential expressed genes between failing and non
      failing groups, and between responder and non-responder groups respectively.
      Targeted cardiac gene messenger RNA (mRNA) expression was analyzed in proportion
      to the total number of reads. Gene expression profiles from the PGM sequencer
      were validated by performing RNA sequencing (RNAseq) with the Illumina Hiseq2500
      sequencing system. RESULTS: The failing sample population was 75% male with an
      average age of 50 and a left ventricular ejection fraction (LVEF) of 16%. Myosin
      light chain kinase (MYLK) and interleukin (IL)-6 genes expression were
      significantly higher in LVAD responders compared to non-responders. Thirty-six
      cardiac genes were expressed differentially between failing and non-failing
      hearts (23 decreased, 13 elevated). MYLK, Beta-1 adrenergic receptor (ADRB1) and
      myosin heavy chain (MYH)-6 expression were among those significantly decreased in
      failing hearts compared to non-failing hearts. Natriuretic peptide B (NPPB) and
      IL-6 were significantly elevated. Targeted gene expression profiles obtained from
      the Ion torrent PGM sequencer were consistent with those obtained from Illumina
      HiSeq2500 sequencing system. CONCLUSIONS: Heart failure is associated with a
      network of transcriptional changes involving contractile proteins, metabolism,
      adrenergic receptors, protein phosphorylation, and signaling factors. Myocardial
      MYLK and IL-6 expression are positively correlated with ejection fraction (EF)
      response to LVAD placement. Targeted RNA sequencing of myocardial gene expression
      can be utilized to predict responders to LVAD therapy and to better characterize
      transcriptional changes in human heart failure.

PMID- 27884157
TI  - Manual versus Automated moNitoring Accuracy of GlucosE II (MANAGE II).
AB  - BACKGROUND: Intravascular continuous glucose monitoring (CGM) may facilitate
      glycemic control in the intensive care unit (ICU). We compared the accuracy of a
      CGM device (OptiScanner(r)) with a standard reference method. METHODS: Adult
      patients who had blood glucose (BG) levels >150 mg/dl and required insertion of
      an arterial and central venous catheter were included. The OptiScanner(r) was
      inserted into a multiple-lumen central venous catheter. Patients were treated
      using a dynamic-scale insulin algorithm to achieve BG values between 80 and 150
      mg/dl. The BG values measured by the OptiScanner(r) were plotted against BG
      values measured using a reference analyzer. The correlation between the BG values
      measured using the two methods and the clinical relevance of any differences were
      assessed using the coefficient of determination (r 2) and the Clarke error grid,
      respectively; bias was assessed by the mean absolute relative difference (MARD).
      Three different standards of glucose monitoring were used to assess accuracy.
      Glycemic control was assessed using the time in range (TIR). Six indices of
      glycemic variability were calculated. RESULTS: The analysis included 929 paired
      samples from 88 patients, monitored for a total of 2584 hours. Reference BG
      values ranged between 60 and 484 mg/dl. The r 2 value was 0.89. The percentage of
      BG values within zones A and B of the Clarke error grid was 99.9%; the MARD was
      7.7%. Using the ISO 15197 standard and Food and Drug Administration and consensus
      standards, respectively, 80.4% of measurements were within 15 mg/dl and 88.2%
      within 15% of reference values, 40% of measurements were within 7 mg/dl and 72.5%
      within 10% of reference values, and 65.2% of measurements were within 10 mg/dl
      and 82.7% within 12.5% of reference values. The TIR was slightly lower with the
      OptiScanner(r) than with the reference method. The J-index, standard deviation
      and maximal glucose change were the indices of glycemic variability least
      affected by the measurement device. CONCLUSIONS: Based on the MARD, the
      performance of the OptiScanner(r) is adequate for use in ICU patients. Because
      recent standards for accuracy were not met, the OptiScanner(r) should not be used
      as a sole monitor. The assessment of glycemic variability is influenced by the
      time interval between BG determinations. TRIAL REGISTRATION: Clinicaltrials.gov
      NCT01720381 . Registered 31 October 2012.

PMID- 27884158
TI  - Rapid visualization of latent fingermarks using gold seed-mediated enhancement.
AB  - BACKGROUND: Fingermarks are one of the most important and useful forms of
      physical evidence in forensic investigations. However, latent fingermarks are not
      directly visible, but can be visualized due to the presence of other residues
      (such as inorganic salts, proteins, polypeptides, enzymes and human metabolites)
      which can be detected or recognized through various strategies. Convenient and
      rapid techniques are still needed to provide obvious contrast between the
      background and the fingermark ridges and to then visualize latent fingermark with
      a high degree of selectivity and sensitivity. RESULTS: In this work, lysozyme
      binding aptamer-conjugated Au nanoparticles (NPs) are used to recognize and
      target lysozyme in the fingermark ridges, and Au+-complex solution is used as a
      growth agent to reduce Au+ from Au+ to Au0 on the surface of the Au NPs. Distinct
      fingermark patterns were visualized on a range of professional forensic within 3
      min; the resulting images could be observed by the naked eye without background
      interference. The entire processes from fingermark collection to visualization
      only entails two steps and can be completed in less than 10 min. The proposed
      method provides cost and time savings over current fingermark visualization
      methods. CONCLUSIONS: We report a simple, inexpensive, and fast method for the
      rapid visualization of latent fingermarks on the non-porous substrates using Au
      seed-mediated enhancement. Au seed-mediated enhancement is used to achieve the
      rapid visualization of latent fingermarks on non-porous substrates by the naked
      eye without the use of expensive or sophisticated instruments. The proposed
      approach offers faster detection and visualization of latent fingermarks than
      existing methods. The proposed method is expected to increase detection
      efficiency for latent fingermarks and reduce time requirements and costs for
      forensic investigations.

PMID- 27884159
TI  - Monoacylglycerol lipase promotes progression of hepatocellular carcinoma via NF
      kappaB-mediated epithelial-mesenchymal transition.
AB  - BACKGROUND: Monoacylglycerol lipase (MAGL), a critical lipolytic enzyme, has
      emerged as a key regulator of tumor progression, yet its biological function and
      clinical significance in hepatocellular carcinoma (HCC) is still unknown.
      METHODS: In this study, we used a tissue microarray containing samples from 170
      HCC patients to evaluate the expression of MAGL and its correlation with other
      clinicopathologic characteristics. In addition, we investigated the regulating
      effects of MAGL on various HCC lines. Finally, we identified the NF-kappaB
      signaling pathway participated in MAGL-mediated epithelial-mesenchymal transition
      (EMT) using HCC cell lines with different metastatic potentials. RESULTS: The
      expression of MAGL was significantly higher in HCC tumors than in matched
      peritumor tissues. Specifically, high MAGL expression was found in tumors with
      larger tumor size, microvascular invasion, poor differentiation, or advanced TNM
      stage. In addition, the clinical prognosis for the MAGLhigh group was markedly
      poorer than that for the MAGLlow group in the 1-, 3-, and 5-year overall survival
      times and recurrence rates of HCC patients. MAGL expression was an independent
      prognostic factor for both survival and recurrence after curative resection.
      Furthermore, the upregulation of MAGL in HCC cells promoted cell growth and
      invasiveness abilities, and accompanied by EMT. In contrast, downregulation of
      MAGL obviously inhibited these characteristics. Moreover, further investigations
      verified that MAGL facilitates HCC progression via NF-kappaB-mediated EMT
      process. CONCLUSIONS: Our findings demonstrate MAGL could promote HCC progression
      by the induction of EMT and suggest a potential therapeutic target, as well as a
      biomarker for prognosis, in patients with HCC.

PMID- 27884162
TI  - 'The stars seem aligned': a qualitative study to understand the effects of
      context on scale-up of maternal and newborn health innovations in Ethiopia, India
      and Nigeria.
AB  - BACKGROUND: Donors commonly fund innovative interventions to improve health in
      the hope that governments of low and middle-income countries will scale-up those
      that are shown to be effective. Yet innovations can be slow to be adopted by
      country governments and implemented at scale. Our study explores this problem by
      identifying key contextual factors influencing scale-up of maternal and newborn
      health innovations in three low-income settings: Ethiopia, the six states of
      northeast Nigeria and Uttar Pradesh state in India. METHODS: We conducted 150
      semi-structured interviews in 2012/13 with stakeholders from government,
      development partner agencies, externally funded implementers including civil
      society organisations, academic institutions and professional associations to
      understand scale-up of innovations to improve the health of mothers and newborns
      these study settings. We analysed interview data with the aid of a common
      analytic framework to enable cross-country comparison, with Nvivo to code themes.
      RESULTS: We found that multiple contextual factors enabled and undermined
      attempts to catalyse scale-up of donor-funded maternal and newborn health
      innovations. Factors influencing government decisions to accept innovations at
      scale included: how health policy decisions are made; prioritising and funding
      maternal and newborn health; and development partner harmonisation. Factors
      influencing the implementation of innovations at scale included: health systems
      capacity in the three settings; and security in northeast Nigeria. Contextual
      factors influencing beneficiary communities' uptake of innovations at scale
      included: sociocultural contexts; and access to healthcare. CONCLUSIONS: We
      conclude that context is critical: externally funded implementers need to assess
      and adapt for contexts if they are to successfully position an innovation for
      scale-up.

PMID- 27884160
TI  - The D Domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits
      MEK/ERK activation in glioma cells.
AB  - BACKGROUND: As a well-characterized key player in various signal transduction
      networks, extracellular-signal-regulated kinase (ERK1/2) has been widely
      implicated in the development of many malignancies. We previously found that
      Leucine-rich repeat containing 4 (LRRC4) was a tumor suppressor and a negative
      regulator of the ERK/MAPK pathway in glioma tumorigenesis. However, the precise
      molecular role of LRRC4 in ERK signal transmission is unclear. METHODS: The
      interaction between LRRC4 and ERK1/2 was assessed by co-immunoprecipitation and
      GST pull-down assays in vivo and in vitro. We also investigated the interaction
      of LRRC4 and ERK1/2 and the role of the D domain in ERK activation in glioma
      cells. RESULTS: Here, we showed that LRRC4 and ERK1/2 interact via the D domain
      and CD domain, respectively. Following EGF stimuli, the D domain of LRRC4 anchors
      ERK1/2 in the cytoplasm and abrogates ERK1/2 activation and nuclear
      translocation. In glioblastoma cells, ectopic LRRC4 expression competitively
      inhibited the interaction of endogenous mitogen-activated protein kinase (MEK)
      and ERK1/2. Mutation of the D domain decreased the LRRC4-mediated inhibition of
      MAPK signaling and its anti-proliferation and anti-invasion roles. CONCLUSIONS:
      Our results demonstrated that the D domain of LRRC4 anchors ERK1/2 in the
      cytoplasm and competitively inhibits MEK/ERK activation in glioma cells. These
      findings identify a new mechanism underlying glioblastoma progression and suggest
      a novel therapeutic strategy by restoring the activity of LRRC4 to decrease MAPK
      cascade activation.

PMID- 27884161
TI  - HPV16 integration probably contributes to cervical oncogenesis through
      interrupting tumor suppressor genes and inducing chromosome instability.
AB  - BACKGROUND: The integration of human papilloma virus (HPV) into host genome is
      one of the critical steps that lead to the progression of precancerous lesion
      into cancer. However, the mechanisms and consequences of such integration events
      are poorly understood. This study aims to explore those questions by studying
      high risk HPV16 integration in women with cervical intraepithelial neoplasia
      (CIN) and cervical squamous cell carcinoma (SCC). METHODS: Specifically, HPV
      integration status of 13 HPV16-infected patients were investigated by ligation
      mediated PCR (DIPS-PCR) followed by DNA sequencing. RESULTS: In total, 8 HPV16
      integration sites were identified inside or around genes associated with cancer
      development. In particular, the well-studied tumor suppressor genes SCAI was
      found to be integrated by HPV16, which would likely disrupt its expression and
      therefore facilitate the migration of tumor. On top of that, we observed several
      cases of chromosome translocation events coincide with HPV integration, which
      suggests the existence of chromosome instability. Additionally, short overlapping
      sequences were observed between viral derived and host derived fragments in viral
      cellular junctions, indicating that integration was mediated by micro homology
      mediated DNA repair pathway. CONCLUSIONS: Overall, our study suggests a model in
      which HPV16 might contribute to oncogenesis not only by disrupting tumor
      suppressor genes, but also by inducing chromosome instability.

PMID- 27884164
TI  - Hyaluronan synthase 2 expressed by cancer-associated fibroblasts promotes oral
      cancer invasion.
AB  - BACKGROUND: Hyaluronan synthases (HAS) control the biosynthesis of hyaluronan
      (HA) and critically modulate the tumor microenviroment. Cancer-associated
      fibroblasts (CAFs) affect the progression of a tumor by remolding the matrix.
      However, little is known about the role of HAS from CAFs in this process. This
      study aimed to determine the role of hyaluronan synthase 2 (HAS2) from CAFs in
      the progression of oral squamous cell carcinoma (OSCC) invasion. METHODS: HAS
      isoforms 1, 2, and 3 in paired sets of CAFs and normal fibroblasts (NFs) were
      examined by real-time PCR, and the expression of HAS2 and alpha-SMA in OSCC
      tissue sections was further evaluated using immunohistochemical staining.
      Furthermore, we used a conditioned culture medium model to evaluate the effects
      of HAS2 from CAFs on the invasion and epithelial-mesenchymal transition (EMT) of
      the oral cancer cells Cal27. Finally, we compared the expression of matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs)
      between CAFs and NF, and between CAFs with or without HAS2 knockdown using an
      antibody array and western blotting. RESULTS: CAFs expressed higher levels of
      HAS2 than the paired NFs. HAS2 expression was consistent with alpha-SMA-positive
      myofibroblasts in the stroma of OSCC, and these were significantly correlated
      advanced clinical stages and cervical lymph node metastasis. Knocking down HAS2
      with a specific siRNA or treatment with a HAS inhibitor markedly attenuated CAF
      induced invasion and EMT of Cal27 cells. Higher MMP1 and lower TIMP1 levels were
      detected in the supernatants of CAFs relative to NFs. Knocking down HAS2 could
      decrease the expression of MMP1 and increase that of TIMP1 in CAFs. CONCLUSIONS:
      HAS2 is one of the key regulators responsible for CAF-mediated OSCC progression
      and acts by modulating the balance of MMP1 and TIMP1.

PMID- 27884163
TI  - Chronic adiponectin deficiency leads to Alzheimer's disease-like cognitive
      impairments and pathologies through AMPK inactivation and cerebral insulin
      resistance in aged mice.
AB  - BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2
      diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's
      disease (AD). Increasing evidence suggests that insulin resistance plays an
      important role in AD pathogenesis, possibly due to abnormal GSK3beta activation,
      causing intra- and extracellular amyloid-beta (Abeta) accumulation. Adiponectin
      (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects.
      Reduced circulatory APN level is associated with insulin resistance and T2DM. The
      role of APN in AD has not been elucidated. In this study, we aim to examine if
      adiponectin deficiency would lead to cerebral insulin resistance, cognitive
      decline and Alzheimer's-like pathology in mice. METHODS: To study the role of
      adiponectin in cognitive functions, we employed adiponectin-knockout (APN-KO)
      mice and demonstrated chronic APN deficiency in their CNS. Behavioral tests were
      performed to study the cognitions of male APN-KO mice. Brains and tissue lysates
      were collected to study the pathophysiological and molecular changes in the brain
      of APN-KO mice. SH-SY5Y neuroblastoma cell line was used to study the molecular
      mechanism upon APN and insulin treatment. RESULTS: Aged APN-deficient mice
      displayed spatial memory and learning impairments, fear-conditioned memory
      deficit as well as anxiety. These mice also developed AD pathologies including
      increased cerebral Abeta42 level, Abeta deposition, hyperphosphorylated Tau
      proteins, microgliosis and astrogliosis with increased cerebral IL-1beta and
      TNFalpha levels that associated with increased neuronal apoptosis and reduced
      synaptic proteins levels, suggesting APN deficiency may lead to neuronal and
      synaptic loss in the brain. AD pathologies-associated APN-KO mice displayed
      attenuated AMPK phosphorylation and impaired insulin signaling including
      decreased Akt induction and increased GSK3beta activation in the hippocampus and
      frontal cortex. Aged APN-KO mice developed hippocampal insulin resistance with
      reduced pAkt induction upon intracerebral insulin injection. Consistently, APN
      treatment in SH-SY5Y cells with insulin resistance and overexpressing Abeta
      induce higher pAkt levels through AdipoR1 upon insulin treatment whereas the
      induction was blocked by compound C, indicating APN can enhance neuronal insulin
      sensitivity through AMPK activation. CONCLUSION: Our results indicated that
      chronic APN deficiency inactivated AMPK causing insulin desensitization and
      elicited AD-like pathogenesis in aged mice which also developed significant
      cognitive impairments and psychiatric symptoms.

PMID- 27884165
TI  - Implementing an evidence-based computerized decision support system linked to
      electronic health records to improve care for cancer patients: the ONCO-CODES
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Computerized decision support systems (CDSSs) are computer programs
      that provide doctors with person-specific, actionable recommendations, or
      management options that are intelligently filtered or presented at appropriate
      times to enhance health care. CDSSs might be integrated with patient electronic
      health records (EHRs) and evidence-based knowledge. METHODS/DESIGN: The
      Computerized DEcision Support in ONCOlogy (ONCO-CODES) trial is a pragmatic,
      parallel group, randomized controlled study with 1:1 allocation ratio. The trial
      is designed to evaluate the effectiveness on clinical practice and quality of
      care of a multi-specialty collection of patient-specific reminders generated by a
      CDSS in the IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei
      Tumori (IRST) hospital. We hypothesize that the intervention can increase
      clinician adherence to guidelines and, eventually, improve the quality of care
      offered to cancer patients. The primary outcome is the rate at which the issues
      reported by the reminders are resolved, aggregating specialty and primary care
      reminders. We will include all the patients admitted to hospital services. All
      analyses will follow the intention-to-treat principle. DISCUSSION: The results of
      our study will contribute to the current understanding of the effectiveness of
      CDSSs in cancer hospitals, thereby informing healthcare policy about the
      potential role of CDSS use. Furthermore, the study will inform whether CDSS may
      facilitate the integration of primary care in cancer settings, known to be
      usually limited. The increasing use of and familiarity with advanced technology
      among new generations of physicians may support integrated approaches to be
      tested in pragmatic studies determining the optimal interface between primary and
      oncology care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02645357.

PMID- 27884166
TI  - TIGAR cooperated with glycolysis to inhibit the apoptosis of leukemia cells and
      associated with poor prognosis in patients with cytogenetically normal acute
      myeloid leukemia.
AB  - BACKGROUND: Cancer cells show increased glycolysis and take advantage of this
      metabolic pathway to generate ATP. The TP53-induced glycolysis and apoptosis
      regulator (TIGAR) inhibits aerobic glycolysis and protects tumor cells from
      intracellular reactive oxygen species (ROS)-associated apoptosis. However, the
      function of TIGAR in glycolysis and survival of acute myeloid leukemia cells
      remains unclear. METHODS: We analyzed TIGAR expression in cytogenetically normal
      (CN-) AML patients and the correlations with clinical and biological parameters.
      In vivo and in vitro, we tested whether glycolysis may induce TIGAR expression
      and evaluated the combination effect of glycolysis inhibitor and TIGAR knockdown
      on human leukemia cell proliferation. RESULTS: High TIGAR expression was an
      independent predictor of poor survival and high incidence of relapse in adult
      patients with CN-AML. TIGAR also showed high expression in multiple human
      leukemia cell lines and knockdown of TIGAR activated glycolysis through PFKFB3
      upregulation in human leukemia cells. Knockdown of TIGAR inhibited the
      proliferation of human leukemia cells and sensitized leukemia cells to glycolysis
      inhibitor both in vitro and in vivo. Furthermore, TIGAR knockdown in combination
      with glycolysis inhibitor 2-DG led leukemia cells to apoptosis. In addition, the
      p53 activator Nutlin-3alpha showed a significant combinational effect with TIGAR
      knockdown in leukemia cells. However, TIGAR expression and its anti-apoptotic
      effects were uncoupled from overexpression of exogenous p53 in leukemia cells.
      CONCLUSIONS: TIGAR might be a predictor of poor survival and high incidence of
      relapse in AML patients, and the combination of TIGAR inhibitors with anti
      glycolytic agents may be novel therapies for the future clinical use in AML
      patients.

PMID- 27884167
TI  - Rett syndrome - biological pathways leading from MECP2 to disorder phenotypes.
AB  - Rett syndrome (RTT) is a rare disease but still one of the most abundant causes
      for intellectual disability in females. Typical symptoms are onset at month 6-18
      after normal pre- and postnatal development, loss of acquired skills and severe
      intellectual disability. The type and severity of symptoms are individually
      highly different. A single mutation in one gene, coding for methyl-CpG-binding
      protein 2 (MECP2), is responsible for the disease. The most important action of
      MECP2 is regulating epigenetic imprinting and chromatin condensation, but MECP2
      influences many different biological pathways on multiple levels although the
      molecular pathways from gene to phenotype are currently not fully understood. In
      this review the known changes in metabolite levels, gene expression and
      biological pathways in RTT are summarized, discussed how they are leading to some
      characteristic RTT phenotypes and therefore the gaps of knowledge are identified.
      Namely, which phenotypes have currently no mechanistic explanation leading back
      to MECP2 related pathways? As a result of this review the visualization of the
      biologic pathways showing MECP2 up- and downstream regulation was developed and
      published on WikiPathways which will serve as template for future omics data
      driven research. This pathway driven approach may serve as a use case for other
      rare diseases, too.

PMID- 27884169
TI  - Study protocol: implementation of a computer-assisted intervention for autism in
      schools: a hybrid type II cluster randomized effectiveness-implementation trial.
AB  - BACKGROUND: The number of children diagnosed with autism has rapidly outpaced the
      capacities of many public school systems to serve them, especially under
      resourced, urban school districts. The intensive nature of evidence-based autism
      interventions, which rely heavily on one-to-one delivery, has caused schools to
      turn to computer-assisted interventions (CAI). There is little evidence regarding
      the feasibility, effectiveness, and implementation of CAI in public schools.
      While CAI has the potential to increase instructional time for students with
      autism, it may also result in unintended consequences such as reduction in the
      amount of interpersonal (as opposed to computerized) instruction students
      receive. The purpose of this study is to test the effectiveness of one such CAI
      TeachTown-its implementation, and its effects on teachers' use of other evidence
      based practices. METHODS: This study protocol describes a type II hybrid cluster
      randomized effectiveness-implementation trial. We will train and coach 70
      teachers in autism support classrooms in one large school district in the use of
      evidence-based practices for students with autism. Half of the teachers then will
      be randomly selected to receive training and access to TeachTown: Basics, a CAI
      for students with autism, for the students in their classrooms. The study
      examines: (1) the effectiveness of TeachTown for students with autism; (2) the
      extent to which teachers implement TeachTown the way it was designed (i.e.,
      fidelity); and (3) whether its uptake increases or reduces the use of other
      evidence-based practices. DISCUSSION: This study will examine the implementation
      of new technology for children with ASD in public schools and will be the first
      to measure the effectiveness of CAI. As importantly, the study will investigate
      whether adding a new technology on top of existing practices increases or
      decreases their use. This study presents a unique method to studying both the
      implementation and exnovation of evidence-based practices for children with
      autism in school settings. TRIAL REGISTRATION: NCT02695693 . Retrospectively
      registered on July 8, 2016.

PMID- 27884170
TI  - First report of Rickettsia raoultii and R. slovaca in Melophagus ovinus, the
      sheep ked.
AB  - BACKGROUND: Melophagus ovinus (Diptera: Hippoboscidae), a hematophagous
      ectoparasite, is mainly found in Europe, Northwestern Africa, and Asia. This
      wingless fly infests sheep, rabbits, and red foxes, and causes inflammation, wool
      loss and skin damage. Furthermore, this parasite has been shown to transmit
      diseases, and plays a role as a vector. Herein, we investigated the presence of
      various Rickettsia species in M. ovinus. METHODS: In this study, a total of 95
      sheep keds were collected in Kuqa County and Alaer City southern region of
      Xinjiang Uygur Autonomous Region, northwestern China. First, collected sheep keds
      were identified on the species level using morphological keys and molecular
      methods based on a fragment of the 18S ribosomal DNA gene (18S rDNA). Thereafter,
      to assess the presence of rickettsial DNA in sheep keds, the DNA of individual
      samples was screened by PCR based on six Rickettsia-specific gene fragments
      originating from six genes: the 17-kilodalton antigen gene (17-kDa), 16S rRNA
      gene (rrs), surface cell antigen 4 gene (sca4), citrate synthase gene (gltA), and
      outer membrane protein A and B genes (ompA and ompB). The amplified products were
      confirmed by sequencing and BLAST analysis (
      https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&PAGE_TYPE=BlastSearch&LIN
      _LOC=blasthome ). RESULTS: According to its morphology and results of molecular
      analysis, the species was identified as Melophagus ovinus, with 100% identity to
      M. ovinus from St. Kilda, Australia (FN666411). DNA of Rickettsia spp. were found
      in 12 M. ovinus samples (12.63%, 12/95). Rickettsia raoultii and R. slovaca were
      confirmed based on phylogenetic analysis, although the genetic markers of these
      two rickettsial agents amplified in this study showed molecular diversity.
      CONCLUSIONS: This is the first report of R. raoultii and R. slovaca DNA in M.
      ovinus. Rickettsia slovaca was found for the first time around the Taklimakan
      Desert located in China. This finding extends the geographical range of spotted
      fever group rickettsiae.

PMID- 27884172
TI  - Spatial distribution and trypanosome infection of tsetse flies in the sleeping
      sickness focus of Zimbabwe in Hurungwe District.
AB  - BACKGROUND: In Zimbabwe, cases of human African trypanosomiasis (HAT) are caused
      by the unicellular protozoan Trypanosoma brucei, sub-species T. b. rhodesiense.
      They are reported from the tsetse-infested area in the northern part of the
      country, broadly corresponding to the valley of the Zambezi River. Tsetse
      transmitted trypanosomes, in particular T. congolense and T. vivax, also cause
      morbidity and mortality in livestock, thus generating poverty and food
      insecurity. Two species of tsetse fly, Glossina morsistans morsitans and G.
      pallidipes, are known to be present in the Zambezi Valley, although their
      distributional patterns and densities have not been investigated in detail. The
      present study tries to address this gap by providing some insight into the
      dynamics of trypanosomiasis in humans and livestock. METHODS: Tsetse distribution
      and trypanosome infections were studied using traps and fixed fly rounds located
      at 10 km intervals along a 110 km long transect straddling the southern
      escarpment of the Zambezi Valley. Three km long fly rounds were conducted on 12
      sites, and were repeated 11 times over a 7-month period. Additional traps were
      deployed and monitored in selected sites. Microscopic examination of 2092 flies
      for trypanosome infections was conducted. RESULTS: Surveys confirmed the presence
      of G. morsitans morsitans and G. pallidipes in the Zambezi Valley floor. Moving
      south, the apparent density of tsetse flies appears to peak in the vicinity of
      the escarpment, then drops on the highlands. Only one fly was caught south of the
      old game fence separating protected and settled areas. A trypanosome infection
      rate of 6.31% was recorded in tsetse flies dissected. Only one infection of the
      T. brucei-type was detected. CONCLUSIONS: Tsetse fly distribution in the study
      area appears to be driven by ecological factors such as variation in land use and
      altitude-mediated climatic patterns. Although targeted control of tsetse flies
      have played a role in determining distribution, no major control operations have
      been implemented in the area for 15 years. Trypanosome infections in tsetse flies
      are consistent with HAT epidemiological data, which considers the situation to be
      generally 'low risk'. Nonetheless, underreporting is likely to conceal the true
      epidemiological picture, and efforts are needed to strengthen the diagnostic
      capacities of health facilities.

PMID- 27884168
TI  - Ataxia telangiectasia: a review.
AB  - DEFINITION OF THE DISEASE: Ataxia telangiectasia (A-T) is an autosomal recessive
      disorder primarily characterized by cerebellar degeneration, telangiectasia,
      immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often
      referred to as a genome instability or DNA damage response syndrome.
      EPIDEMIOLOGY: The world-wide prevalence of A-T is estimated to be between 1 in
      40,000 and 1 in 100,000 live births. CLINICAL DESCRIPTION: A-T is a complex
      disorder with substantial variability in the severity of features between
      affected individuals, and at different ages. Neurological symptoms most often
      first appear in early childhood when children begin to sit or walk. They have
      immunological abnormalities including immunoglobulin and antibody deficiencies
      and lymphopenia. People with A-T have an increased predisposition for cancers,
      particularly of lymphoid origin. Pulmonary disease and problems with feeding,
      swallowing and nutrition are common, and there also may be dermatological and
      endocrine manifestations. ETIOLOGY: A-T is caused by mutations in the ATM (Ataxia
      Telangiectasia, Mutated) gene which encodes a protein of the same name. The
      primary role of the ATM protein is coordination of cellular signaling pathways in
      response to DNA double strand breaks, oxidative stress and other genotoxic
      stress. DIAGNOSIS: The diagnosis of A-T is usually suspected by the combination
      of neurologic clinical features (ataxia, abnormal control of eye movement, and
      postural instability) with one or more of the following which may vary in their
      appearance: telangiectasia, frequent sinopulmonary infections and specific
      laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T
      lymphocytes and increased alpha-fetoprotein levels). Because certain neurological
      features may arise later, a diagnosis of A-T should be carefully considered for
      any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be
      confirmed by the finding of an absence or deficiency of the ATM protein or its
      kinase activity in cultured cell lines, and/or identification of the pathological
      mutations in the ATM gene. DIFFERENTIAL DIAGNOSIS: There are several other
      neurologic and rare disorders that physicians must consider when diagnosing A-T
      and that can be confused with A-T. Differentiation of these various disorders is
      often possible with clinical features and selected laboratory tests, including
      gene sequencing. ANTENATAL DIAGNOSIS: Antenatal diagnosis can be performed if the
      pathological ATM mutations in that family have been identified in an affected
      child. In the absence of identifying mutations, antenatal diagnosis can be made
      by haplotype analysis if an unambiguous diagnosis of the affected child has been
      made through clinical and laboratory findings and/or ATM protein analysis.
      GENETIC COUNSELING: Genetic counseling can help family members of a patient with
      A-T understand when genetic testing for A-T is feasible, and how the test results
      should be interpreted. MANAGEMENT AND PROGNOSIS: Treatment of the neurologic
      problems associated with A-T is symptomatic and supportive, as there are no
      treatments known to slow or stop the neurodegeneration. However, other
      manifestations of A-T, e.g. immunodeficiency, pulmonary disease, failure to
      thrive and diabetes can be treated effectively.

PMID- 27884171
TI  - Molecular characterization and protective efficacy of silent information
      regulator 2A from Eimeria tenella.
AB  - BACKGROUND: Silent information regulator 2 (SIR2) proteins are a family of NAD + 
      dependent protein deacetylases that are considered potential targets for anti
      parasitic agents. In this study, we cloned and characterized SIR2A of the
      protozoan parasite Eimeria tenella (EtSIR2A) and investigated its protective
      efficacy as a DNA vaccine. METHODS: The EtSIR2A gene encoding 33.37 kDa protein
      from E. tenella second-generation merozoites was cloned, and recombinant EtSIR2A
      protein (rEtSIR2A) was produced in an Escherichia coli expression system. The
      rEtSIR2A was used to immunize rabbits. Anti-rEtSIR2A antibodies were used to
      determine the immunolocolization of EtSIR2A in the parasite by immunofluorescence
      assay (IFA). Transcript and protein expression of EtSIR2A in different
      development stages of E. tenella were observed by quantitative real-time PCR
      (qPCR) and western blot (WB) analysis, respectively. The recombinant plasmid
      pCAGGS-EtSIR2A was constructed and its efficacy against E. tenella infection in
      chickens was evaluated. RESULTS: qPCR and WB analysis revealed EtSIR2A expression
      was developmentally regulated at both the mRNA and protein levels. EtSIR2A mRNA
      levels were higher in unsporulated oocysts than at other developmental stages,
      including sporulated oocysts, sporozoites and second-generation merozoites. In
      contrast, EtSIR2A protein expression levels were highest in second-generation
      merozoites, moderate in unsporulated oocysts and sporulated oocysts and lowest in
      sporozoites. Immunostaining with anti-rEtSIR2A antibody indicated that EtSIR2A
      was mainly located in the cytoplasm of sporozoites and second-generation
      merozoites, and was strongly expressed during first stage schizogony. Animal
      challenge experiments demonstrated that immunization with pCAGGS-EtSIR2A
      significantly increased average body-weight gain, and decreased mean lesion score
      and oocyst output in chickens. CONCLUSIONS: These results suggest that EtSIR2A
      may play an important role in parasite cell survival and may be an effective
      candidate for the development of new vaccines against E. tenella infection in
      chickens.

PMID- 27884173
TI  - Revisiting the morbid genome of Mendelian disorders.
AB  - BACKGROUND: The pathogenicity of many Mendelian variants has been challenged by
      large-scale sequencing efforts. However, many rare and benign "disease mutations"
      are difficult to analyze due to their rarity. The Saudi Arabian variome is
      enriched for homozygosity due to inbreeding, a key advantage that can be
      exploited for the critical examination of previously published variants. RESULTS:
      We collated all "disease-related mutations" listed in the Human Gene Mutation
      Database (HGMD) and ClinVar, including "variants of uncertain significance"
      (VOUS). We find that the use of public databases including 1000 Genomes, ExAC,
      and Kaviar can reclassify many of these variants as likely benign. Our Saudi
      Human Genome Program (SHGP) can reclassify many variants that are rare in public
      databases. Furthermore, SGPD allows us to observe many previously reported
      variants in the homozygous state and our extensive phenotyping of participants
      makes it possible to demonstrate the lack of phenotype for these variants, thus
      challenging their pathogenicity despite their rarity. We also find that 18 VOUS
      BRCA1 and BRCA2 variants that are listed in BRCA Exchange are present at least
      once in the homozygous state in patients who lack features of Fanconi anemia.
      Reassuringly, we could reciprocally demonstrate that none of those labeled as
      "pathogenic" were observed in the homozygous statue in individuals who lack
      Fanconi phenotype in our database. CONCLUSION: Our study shows the importance of
      revisiting disease-related databases using public resources as well as of
      population-specific resources to improve the specificity of the morbid genome of
      Mendelian diseases in humans.

PMID- 27884174
TI  - Comparative morphological and molecular analysis confirms the presence of the
      West Nile virus mosquito vector, Culex univittatus, in the Iberian Peninsula.
AB  - BACKGROUND: Culex univittatus and Culex perexiguus mosquitoes (Diptera:
      Culicidae) are competent arbovirus vectors, but with unclear morphological
      differentiation. In Europe, and in the Iberian Peninsula in particular, the
      presence of either or both species is controversial. However, in order to conduct
      adequate surveillance for arboviruses in this region, it is crucial to clarify
      whether Cx. univittatus is present or not, as well as to critically assess
      existing differentiation tools. This study aimed to clarify this situation, by
      morphological and molecular phylogenetic comparison of Iberian specimens deemed
      as Cx. univittatus, with others of South African origin, i.e. from the type
      locality region. METHODS: Thus, morphological characteristics useful to
      distinguish both species, such as midfemur pale line, hindfemur R ratio, seta g
      R1 ratio, seta f shape, length of ventral arm of phalosome and number of setae on
      IX tergal abdominal segment, were observed. A phylogenetic analysis based on cox1
      mtDNA, of which there were no sequences from Cx. univittatus yet available in the
      GenBank database, was performed. RESULTS: This analysis showed that Iberian and
      South African specimens are morphologically similar, except for the length of the
      ventral arm of the phalosome, which was higher in the Iberian specimens. Although
      the Iberian specimens could not be accurately identified using BOLD Systems,
      phylogenetic analysis still grouped these closer to South African Cx.
      univittatus, than to Cx. perexiguus from Turkey and Pakistan, despite the
      observed segregation of both taxa as two individual monophyletic clusters with
      shared common ancestry. CONCLUSIONS: This survey demonstrates that the West Nile
      virus vector Cx. univittatus is present in the Iberian Peninsula.

PMID- 27884175
TI  - Network meta-analyses performed by contracting companies and commissioned by
      industry.
AB  - BACKGROUND: Industry commissions contracting companies to perform network meta
      analysis for health technology assessment (HTA) and reimbursement submissions.
      Our objective was to estimate the number of network meta-analyses performed by
      consulting companies contracted by industry, to assess whether they were
      published, and to explore reasons for non-publication. METHODS: We searched
      MEDLINE for network meta-analyses of randomized trials. Papers were included if
      they had authors affiliated with any contracting company. All identified
      contracting companies as well as additional ones from the list of the exhibitors
      at the International Society for Pharmacoeconomics and Outcomes Research, an
      annual meeting that representatives from many contracting companies attend and
      exhibit at, were surveyed regarding conduct and publication of network meta
      analyses. RESULTS: In 162 of 822 (20%) network meta-analysis papers, authors were
      affiliated to 66 contracting companies. Another 36 contracting companies were
      identified by the exhibitors list. Three companies had no contact information and
      six merged with others, therefore 93 companies were contacted. Thirty seven out
      of ninety three (40%) companies responded, and 19 indicated that they had
      performed a total of 476 network meta-analyses, but only 102 (21%) papers were
      published. Thirteen companies that disclosed to have conducted 174 network meta
      analyses (45 published) provided reasons for non-publication. Of the 129 still
      unpublished meta-analyses, for 40 there were plans for future publication, for 37
      the sponsor did not allow publication, for 16 the contracting companies did not
      plan to publish the meta-analysis, for another 23 plans were unclear, and the
      remaining 13 were used as HTA submission. The protocol of the network meta
      analysis was publically available from 11/162 (6.8%) network meta-analyses
      published by authors affiliated with contracting companies. CONCLUSIONS: There is
      a prolific sector of professional contracting companies that perform network meta
      analyses. Industry commissions many network meta-analyses, but most are not
      registered before or published after analyses in the scientific literature.
      Mechanisms to improve publication rates of network meta-analysis commissioned by
      industry are warranted.

PMID- 27884176
TI  - Localization of bleeding sites in patients with hemoptysis based on their chest
      computed tomography findings: a retrospective cohort study.
AB  - BACKGROUND: The aim of this study was to propose a localization strategy for
      bleeding sites in hemoptysis patients using their chest computed tomography (CT)
      findings. METHODS: Between January 2005 and July 2009, the chest CT findings of
      161 hemoptysis patients were retrospectively reviewed. Following chest CT, the
      lobe with the most prominent ground glass attenuation (GGA) or specific lesions
      with the potential to cause pulmonary hemorrhage were analysed to develop a
      localization strategy for bleeding sites. Fibre optic bronchoscopy (FOB) findings
      of active bleeding were used as the standard reference for the bleeding sites.
      RESULTS: The concordance rate between the most prominent GGA and FOB findings was
      higher than that between specific lesions and FOB findings (Kappa value [k] =
      0.751 vs. 0.448, p < 0.001). Among the specific lesions, there were high
      concordance rates between lung cancer and FOB findings (3/3, 100%) and fungus
      balls and FOB findings (8/9, 89%). The agreement of localization of the bleeding
      site between FOB findings and the localization strategy based on chest CT
      findings including the most prominent GGA, lung cancer and fungus balls, showed
      almost perfect (k = 0.904). CONCLUSIONS: The localization of bleeding sites in
      hemoptysis patients could be determined by chest CT findings such as the most
      prominent GGA, malignancy and fungus ball.

PMID- 27884177
TI  - LRRK2 contributes to monocyte dysregulation in Parkinson's disease.

PMID- 27884179
TI  - Factors related to renal cortical atrophy development after glucocorticoid
      therapy in IgG4-related kidney disease: a retrospective multicenter study.
AB  - BACKGROUND: In immunoglobulin G4-related kidney disease (IgG4-RKD), focal or
      diffuse renal cortical atrophy is often observed in the clinical course after
      glucocorticoid therapy. This study aimed to clarify the factors related to renal
      atrophy after glucocorticoid therapy in IgG4-RKD. METHODS: We retrospectively
      evaluated clinical features including laboratory data and computed tomography
      (CT) findings before and after glucocorticoid therapy in 23 patients diagnosed
      with IgG4-RKD, all of whom were followed up for more than 24 months. RESULTS:
      Seventeen patients were men, and six were women (average age 62.0 years). Average
      follow-up period was 54.9 months. The average estimated glomerular filtration
      rate (eGFR) at diagnosis was 81.7 mL/min/1.73 m2. All patients had had multiple
      low-density lesions on contrast-enhanced CT before glucocorticoid therapy, and
      showed disappearance or reduction of these lesions after it. Pre-treatment eGFR
      and serum IgE level in 11 patients in whom renal cortical atrophy developed 24
      months after the start of glucocorticoid therapy were significantly different
      from those in 12 patients in whom no obvious atrophy was found at that time (68.9
      +/- 30.1 vs 93.5 +/- 14.1 mL/min/1.73 m2, P = 0.036, and 587 +/- 254 vs 284 +/-
      263 IU/mL, P = 0.008, respectively). Pre-treatment eGFR and serum IgE level were
      also significant risk factors for renal atrophy development 24 months after the
      start of therapy with an odds ratio of 0.520 (per 10 mL/min/1.73 m2, 95%
      confidence interval (CI) 0.273-0.993, P = 0.048) and 1.090 (per 10 IU/mL, 95% CI:
      1.013-1.174, P = 0.022), respectively, in age-adjusted, sex-adjusted, serum IgG4
      level-adjusted logistic regression analysis. Receiver operating characteristic
      curve analysis showed that eGFR of less than 71.0 mL/min/1.73 m2 and serum IgE of
      more than 436.5 IU/mL were the most appropriate cutoffs and yielded sensitivity
      of 63.6% and specificity of 100%, and sensitivity of 90.9% and specificity of
      75.0%, respectively, in predicting renal atrophy development. CONCLUSIONS: This
      study suggests that pre-treatment renal insufficiency and serum IgE elevation
      predict renal atrophy development after glucocorticoid therapy in IgG4-RKD.

PMID- 27884180
TI  - The impact of mHealth interventions on health systems: a systematic review
      protocol.
AB  - BACKGROUND: Mobile health (mHealth) has been described as a health enabling tool
      that impacts positively on the health system in terms of improved access, quality
      and cost of health care. The proposed systematic review will examine the impact
      of mHealth on health systems by assessing access, quality and cost of health care
      as indicators. METHODS: The systematic review will include literature from
      various sources including published and unpublished/grey literature. The
      databases to be searched include: PubMed, Cochrane Library, Google Scholar, NHS
      Health Technology Assessment Database and Web of Science. The reference lists of
      studies will be screened and conference proceedings searched for additional
      eligible reports. Literature to be included will have mHealth as the primary
      intervention. Two authors will independently screen the search output, select
      studies and extract data; discrepancies will be resolved by consensus and
      discussion with the assistance of the third author. DISCUSSION: The systematic
      review will inform policy makers, investors, health professionals, technologists
      and engineers about the impact of mHealth in strengthening the health system. In
      particular, it will focus on three metrics to determine whether mHealth
      strengthens the health system, namely quality of, access to and cost of health
      care services. Systematic review registration: PROSPERO CRD42015026070.

PMID- 27884178
TI  - Patterns of ribosomal protein expression specify normal and malignant human
      cells.
AB  - BACKGROUND: Ribosomes are highly conserved molecular machines whose core
      composition has traditionally been regarded as invariant. However, recent studies
      have reported intriguing differences in the expression of some ribosomal proteins
      (RPs) across tissues and highly specific effects on the translation of individual
      mRNAs. RESULTS: To determine whether RPs are more generally linked to cell
      identity, we analyze the heterogeneity of RP expression in a large set of human
      tissues, primary cells, and tumors. We find that about a quarter of human RPs
      exhibit tissue-specific expression and that primary hematopoietic cells display
      the most complex patterns of RP expression, likely shaped by context-restricted
      transcriptional regulators. Strikingly, we uncover patterns of dysregulated
      expression of individual RPs across cancer types that arise through copy number
      variations and are predictive for disease progression. CONCLUSIONS: Our study
      reveals an unanticipated plasticity of RP expression across normal and malignant
      human cell types and provides a foundation for future characterization of
      cellular behaviors that are orchestrated by specific RPs.

PMID- 27884182
TI  - Operations research for resource planning and -use in radiotherapy: a literature
      review.
AB  - BACKGROUND: The delivery of radiotherapy (RT) involves the use of rather
      expensive resources and multi-disciplinary staff. As the number of cancer
      patients receiving RT increases, timely delivery becomes increasingly difficult
      due to the complexities related to, among others, variable patient inflow,
      complex patient routing, and the joint planning of multiple resources. Operations
      research (OR) methods have been successfully applied to solve many logistics
      problems through the development of advanced analytical models for improved
      decision making. This paper presents the state of the art in the application of
      OR methods for logistics optimization in RT, at various managerial levels.
      METHODS: A literature search was performed in six databases covering several
      disciplines, from the medical to the technical field. Papers included in the
      review were published in peer-reviewed journals from 2000 to 2015. Data
      extraction includes the subject of research, the OR methods used in the study,
      the extent of implementation according to a six-stage model and the (potential)
      impact of the results in practice. RESULTS: From the 33 papers included in the
      review, 18 addressed problems related to patient scheduling (of which 12 focus on
      scheduling patients on linear accelerators), 8 focus on strategic decision
      making, 5 on resource capacity planning, and 2 on patient prioritization.
      Although calculating promising results, none of the papers reported a full
      implementation of the model with at least a thorough pre-post performance
      evaluation, indicating that, apart from possible reporting bias, implementation
      rates of OR models in RT are probably low. CONCLUSIONS: The literature on OR
      applications in RT covers a wide range of approaches from strategic capacity
      management to operational scheduling levels, and shows that considerable benefits
      in terms of both waiting times and resource utilization are likely to be
      achieved. Various fields can be further developed, for instance optimizing the
      coordination between the available capacity of different imaging devices or
      developing scheduling models that consider the RT chain of operations as a whole
      rather than the treatment machines alone.

PMID- 27884181
TI  - Prevalence, type, and correlates of trauma exposure among adolescent men and
      women in Soweto, South Africa: implications for HIV prevention.
AB  - BACKGROUND: Youth trauma exposure is associated with syndemic HIV risk. We
      measured lifetime prevalence, type, and correlates of trauma experience by gender
      among adolescents living in the HIV hyper-endemic setting of Soweto, South
      Africa. METHODS: Using data from the Botsha Bophelo Adolescent Health Survey
      (BBAHS), prevalence of "ever" experiencing a traumatic event among adolescents
      (aged 14-19) was assessed using a modified Traumatic Event Screening Inventory
      Child (TESI-C) scale (19 items, study alpha = 0.63). We assessed self-reported
      number of potentially traumatic events (PTEs) experienced overall and by gender.
      Gender-stratified multivariable logistic regression models assessed independent
      correlates of 'high PTE score' (>=7 PTEs). RESULTS: Overall, 767/830 (92%)
      participants were included (58% adolescent women). Nearly all (99.7%) reported
      experiencing at least one PTE. Median PTE was 7 [Q1,Q3: 5-9], with no gender
      differences (p = 0.19). Adolescent men reported more violent PTEs (e.g., "seen an
      act of violence in the community") whereas women reported more non-violent
      HIV/AIDS-related PTEs (e.g., "family member or someone close died of HIV/AIDS").
      High PTE score was independently associated with high food insecurity among
      adolescent men and women (aOR = 2.63, 95%CI = 1.36-5.09; aOR = 2.57, 95%CI = 1.55
      4.26, respectively). For men, high PTE score was also associated with older age
      (aOR = 1.40/year, 95%CI = 1.21-1.63); and recently moving to Soweto (aOR = 2.78,
      95%CI = 1.14-6.76). Among women, high PTE score was associated with depression
      using the CES-D scale (aOR = 2.00, 95%CI = 1.31-3.03,) and inconsistent condom
      use vs. no sexual experience (aOR = 2.69, 95%CI = 1.66-4.37). CONCLUSION: Nearly
      all adolescents in this study experienced trauma, with gendered differences in
      PTE types and correlates, but not prevalence. Exposure to PTEs were distributed
      along social and gendered axes. Among adolescent women, associations with
      depression and inconsistent condom use suggest pathways for HIV risk. HIV
      prevention interventions targeting adolescents must address the syndemics of
      trauma and HIV through the scale-up of gender-transformative, youth-centred,
      trauma-informed integrated HIV and mental health services.

PMID- 27884185
TI  - The inescapable question of fairness in Pay-for-performance bonus distribution: a
      qualitative study of health workers' experiences in Tanzania.
AB  - BACKGROUND: During the last decade there has been a growing concern about the
      lack of results in the health sectors of many low income countries. Progress has
      been particularly slow in maternal- and child health. Prompted by the need to
      accelerate progress towards these health outcomes, pay-for- performance (P4P)
      schemes have been initiated in a number of countries. This paper explores the
      perceptions and experiences of health workers with P4P bonus distribution in the
      health system context of rural Tanzania. METHODS: This qualitative study was
      based on the P4P pilot in Pwani Region of Tanzania. The study took place in 11
      health care facilities in Rufiji District. The study informants and participants
      were different cadres of health workers assigned to different outpatient and
      inpatient departments at the health facilities, and local administrators of the
      P4P bonus distribution. Thirty two in-depth interviews (IDIs) with administrators
      and health care workers, and six focus group discussions (FGDs with Reproductive
      and Child Health (RCH) staff, non-RCH staff and non-medical staff were conducted.
      Collected data was analyzed through qualitative content analysis. RESULTS: The
      study found that the bonus distribution modality employed in the P4P programme
      was experienced as fundamentally unjust. The bonuses were calculated according to
      the centrality of the health worker position in meeting targeted indicators,
      drawn from the reproductive and child health (RCH) section. Both RCH staff and
      non-RCH perceived the P4P bonus as unfair. Non-RCH objected to getting less bonus
      than RCH staff, and RCH staff running the targeted RCH services, objected to not
      getting more P4P bonus. Non-RCH staff and health administrators suggested a flat
      rate across board as the fairest way of distributing P4P bonuses. The perceived
      unfairness affected work motivation, undermined teamwork across departments and
      created tensions in the social relations at health facilities. CONCLUSION: Our
      results suggest that the experience of unfairness in the way bonuses are
      distributed and administered at the health facility level undermines the
      legitimacy of the P4P scheme. More importantly, long term tensions and conflicts
      at the workplace may impact negatively on the quality of care which P4P was
      intended to improve. We argue that fairness is a critical factor to the success
      of a P4P scheme and that particular attention should be paid to aspects of
      workplace justice in the design of P4P bonus structures.

PMID- 27884183
TI  - RNA-Sequencing for profiling goat milk transcriptome in colostrum and mature
      milk.
AB  - BACKGROUND: In this work we aimed at sequencing and assembling the goat milk
      transcriptome corresponding at colostrum and 120 days of lactation. To
      reconstruct transcripts we used both the genome as reference, and a de novo
      assembly approach. Additionally, we aimed at identifying the differentially
      expressed genes (DEGs) between the two lactation stages and at analyzing the
      expression of genes involved in oligosaccharides metabolism. RESULTS: A total of
      44,635 different transcripts, organized in 33,757 tentative genes, were obtained
      using the goat genome as reference. A significant sequence similarity match was
      found for 40,353 transcripts (90%) against the NCBI NT and for 35,701 (80%)
      against the NR databases. 68% and 69% of the de novo assembled transcripts, in
      colostrum and 120 days of lactation samples respectively, have a significant
      match with the merged transcriptome obtained using Cufflinks/Cuffmerge. CSN2,
      PAEP, CSN1S2, CSN3, LALBA, TPT1, FTH1, M-SAA3, SPP1, GLYCAM1, EEF1A1, CTSD, FASN,
      RPS29, CSN1S1, KRT19 and CHEK1 were found between the top fifteen highly
      expressed genes. 418 loci were differentially expressed between lactation stages,
      among which 207 and 122 were significantly up- and down-regulated in colostrum,
      respectively. Functional annotation and pathway enrichment analysis showed that
      in goat colostrum somatic cells predominate biological processes involved in
      glycolysis, carbohydrate metabolism, defense response, cytokine activity,
      regulation of cell proliferation and cell death, vasculature development, while
      in mature milk, biological process associated with positive regulation of
      lymphocyte activation and anatomical structure morphogenesis are enriched. The
      analysis of 144 different oligosaccharide metabolism-related genes showed that
      most of these (64%) were more expressed in colostrum than in mature milk, with
      eight expressed at very high levels (SLCA3, GMSD, NME2, SLC2A1, B4GALT1, B3GNT2,
      NANS, HEXB). CONCLUSIONS: To our knowledge, this is the first study comparing
      goat transcriptome of two lactation stages: colostrum and 120 days. Our findings
      suggest putative differences of expression between stages and can be envisioned
      as a base for further research in the topic. Moreover because a higher expression
      of genes involved in immune defense response, carbohydrate metabolism and related
      to oligosaccharide metabolism was identified in colostrum we here corroborate the
      potential of goat milk as a natural source of lactose-derived oligosaccharides
      and for the development of functional foods.

PMID- 27884186
TI  - General practitioners in German metropolitan areas - distribution patterns and
      their relationship with area level measures of the socioeconomic status.
AB  - BACKGROUND: Geographical variation of the general practitioner (GP) workforce is
      known between rural and urban areas. However, data about the variation between
      and within urban areas are lacking. METHOD: We analyzed distribution patterns of
      GP full time equivalents (FTE) in German cities with a population size of more
      than 500,000. We correlated their distribution with area measures of social
      deprivation in order to analyze preferences within neighborhood characteristics.
      For this purpose, we developed two area measures of deprivation: Geodemographic
      Index (GDI) and Cultureeconomic Index (CEI). RESULTS: In total n = 9034.75 FTE
      were included in n = 14 cities with n = 171 districts. FTE were distributed
      equally on inter-city level (mean: 6.49; range: 5.12-7.20; SD: 0.51). However, on
      intra-city level, GP distribution was skewed (mean: 6.54; range: 1.80-43.98; SD:
      3.62). Distribution patterns of FTE per 10^4 residents were significantly
      correlated with GDI (r = -0.49; p < 0.001) and CEI (r = -0.22; p = 0.005).
      Therefore, location choices of GPs were mainly positively correlated with 1)
      central location (r = -0.50; p < 0.001), 2) small household size of population (r
      = -0.50; p < 0.001) and 3) population density (r = 0.35; p < 0.001). CONCLUSION:
      Intra-city distribution of GPs was skewed, which could affect the equality of
      access for the urban population. Furthermore, health services planners should be
      aware of GP location preferences. This could be helpful to better understand and
      plan delivery of health services. Within this process the presented
      Geodemographic Index (GDI) could be of use.

PMID- 27884184
TI  - Dietary patterns of early childhood and maternal socioeconomic status in a unique
      prospective sample from a randomized controlled trial of Prenatal DHA
      Supplementation.
AB  - BACKGROUND: Dietary habits established in early childhood and maternal
      socioeconomic status (SES) are important, complex, interrelated factors that
      influence a child's growth and development. The aim of this study was to define
      the major dietary patterns in a cohort of young US children, construct a maternal
      SES index, and evaluate their associations. METHODS: The diets of 190 children
      from a randomized, controlled trial of prenatal supplementation of
      docosahexaenoic acid (DHA) were recorded at 6-mo intervals from 2-4.5 years by 24
      h dietary recall. Hierarchical cluster analysis of age-adjusted, average daily
      intake of 24 food and beverage groups was used to categorize diet. Unrotated
      factor analysis generated an SES score from maternal race, ethnicity, age,
      education, and neighborhood income. RESULTS: We identified two major dietary
      patterns: "Prudent" and "Western." The 85 (45%) children with a Prudent diet
      consumed more whole grains, fruit, yogurt and low-fat milk, green and non-starchy
      vegetables, and nuts and seeds. Conversely, those with a Western diet had greater
      intake of red meat, discretionary fat and condiments, sweet beverages, refined
      grains, French fries and potato chips, eggs, starchy vegetables, processed meats,
      chicken and seafood, and whole-fat milk. Compared to a Western diet, a Prudent
      diet was associated with one standard deviation higher maternal SES (95% CI: 0.80
      to 1.30). CONCLUSIONS: We found two major dietary patterns of young US children
      and defined a single, continuous axis of maternal SES that differed strongly
      between groups. This is an important first step to investigate how child diet,
      SES, and prenatal DHA supplementation interact to influence health outcomes.
      TRIAL REGISTRATION: NCT00266825 . Prospectively registered on December 15, 2005.

PMID- 27884187
TI  - A simulation study to quantify the impacts of exposure measurement error on air
      pollution health risk estimates in copollutant time-series models.
AB  - BACKGROUND: Exposure measurement error in copollutant epidemiologic models has
      the potential to introduce bias in relative risk (RR) estimates. A simulation
      study was conducted using empirical data to quantify the impact of correlated
      measurement errors in time-series analyses of air pollution and health. METHODS:
      ZIP-code level estimates of exposure for six pollutants (CO, NOx, EC, PM2.5, SO4,
      O3) from 1999 to 2002 in the Atlanta metropolitan area were used to calculate
      spatial, population (i.e. ambient versus personal), and total exposure
      measurement error. Empirically determined covariance of pollutant concentration
      pairs and the associated measurement errors were used to simulate true exposure
      (exposure without error) from observed exposure. Daily emergency department
      visits for respiratory diseases were simulated using a Poisson time-series model
      with a main pollutant RR = 1.05 per interquartile range, and a null association
      for the copollutant (RR = 1). Monte Carlo experiments were used to evaluate the
      impacts of correlated exposure errors of different copollutant pairs. RESULTS:
      Substantial attenuation of RRs due to exposure error was evident in nearly all
      copollutant pairs studied, ranging from 10 to 40% attenuation for spatial error,
      3-85% for population error, and 31-85% for total error. When CO, NOx or EC is the
      main pollutant, we demonstrated the possibility of false positives, specifically
      identifying significant, positive associations for copollutants based on the
      estimated type I error rate. CONCLUSIONS: The impact of exposure error must be
      considered when interpreting results of copollutant epidemiologic models, due to
      the possibility of attenuation of main pollutant RRs and the increased
      probability of false positives when measurement error is present.

PMID- 27884190
TI  - How do you design randomised trials for smaller populations? A framework.
AB  - How should we approach trial design when we can get some, but not all, of the way
      to the numbers required for a randomised phase III trial?We present an ordered
      framework for designing randomised trials to address the problem when the ideal
      sample size is considered larger than the number of participants that can be
      recruited in a reasonable time frame. Staying with the frequentist approach that
      is well accepted and understood in large trials, we propose a framework that
      includes small alterations to the design parameters. These aim to increase the
      numbers achievable and also potentially reduce the sample size target. The first
      step should always be to attempt to extend collaborations, consider broadening
      eligibility criteria and increase the accrual time or follow-up time. The second
      set of ordered considerations are the choice of research arm, outcome measures,
      power and target effect. If the revised design is still not feasible, in the
      third step we propose moving from two- to one-sided significance tests, changing
      the type I error rate, using covariate information at the design stage, re
      randomising patients and borrowing external information.We discuss the benefits
      of some of these possible changes and warn against others. We illustrate, with a
      worked example based on the Euramos-1 trial, the application of this framework in
      designing a trial that is feasible, while still providing a good evidence base to
      evaluate a research treatment.This framework would allow appropriate evaluation
      of treatments when large-scale phase III trials are not possible, but where the
      need for high-quality randomised data is as pressing as it is for common
      diseases.

PMID- 27884189
TI  - SParSE++: improved event-based stochastic parameter search.
AB  - BACKGROUND: Despite the increasing availability of high performance computing
      capabilities, analysis and characterization of stochastic biochemical systems
      remain a computational challenge. To address this challenge, the Stochastic
      Parameter Search for Events (SParSE) was developed to automatically identify
      reaction rates that yield a probabilistic user-specified event. SParSE consists
      of three main components: the multi-level cross-entropy method, which identifies
      biasing parameters to push the system toward the event of interest, the related
      inverse biasing method, and an optional interpolation of identified parameters.
      While effective for many examples, SParSE depends on the existence of a
      sufficient amount of intrinsic stochasticity in the system of interest. In the
      absence of this stochasticity, SParSE can either converge slowly or not at all.
      RESULTS: We have developed SParSE++, a substantially improved algorithm for
      characterizing target events in terms of system parameters. SParSE++ makes use of
      a series of novel parameter leaping methods that accelerate the convergence rate
      to the target event, particularly in low stochasticity cases. In addition, the
      interpolation stage is modified to compute multiple interpolants and to choose
      the optimal one in a statistically rigorous manner. We demonstrate the
      performance of SParSE++ on four example systems: a birth-death process, a
      reversible isomerization model, SIRS disease dynamics, and a yeast polarization
      model. In all four cases, SParSE++ shows significantly improved computational
      efficiency over SParSE, with the largest improvements resulting from analyses
      with the strictest error tolerances. CONCLUSIONS: As researchers continue to
      model realistic biochemical systems, the need for efficient methods to
      characterize target events will grow. The algorithmic advancements provided by
      SParSE++ fulfill this need, enabling characterization of computationally
      intensive biochemical events that are currently resistant to analysis.

PMID- 27884191
TI  - Gender differences in load carriage injuries of Australian army soldiers.
AB  - BACKGROUND: With the removal of gender restrictions and the changing nature of
      warfare potentially increasing female soldier exposure to heavy military load
      carriage, the aim of this research was to determine relative risks and patterns
      of load carriage related injuries in female compared to male soldiers. METHODS:
      The Australian Defence Force Occupational Health, Safety and Compensation
      Analysis and Reporting workplace injury database was searched to identify all
      reported load carriage injuries. Using key search terms, the narrative
      description fields were used as the search medium to identify records of
      interest. Population estimates of the female: male incident rate ratio (IRR) were
      calculated with ninety-five percent confidence interval (95% CI) around the
      population estimate of each IRR determined. RESULTS: Female soldiers sustained
      10% (n = 40) of the 401 reported injuries, with a female to male IRR of 1.02 (95%
      CI 0.74 to 1.41). The most common site of injury for both genders was the back
      (F: n = 11, 27%; M: n = 80, 22%), followed by the foot in female soldiers (n = 8,
      20%) and the ankle (n = 60, 17%) in male soldiers. Fifteen percent (n = 6) of
      injuries in female soldiers and 6% (n = 23) of injuries in males were classified
      as Serious Personal Injuries (SPI) with the lower back the leading site for both
      genders (F: n = 3, 43%: M: n = 8, 29%). The injury risk ratio of SPI for female
      compared to male soldiers was 2.40 (95% CI 0.98 to 5.88). CONCLUSIONS: While both
      genders similarly have the lower back as the leading site of injury while
      carrying load, female soldiers have more injuries to the foot as the second
      leading site of injury, as opposed to ankle injuries in males. The typically
      smaller statures of female soldiers may have predisposed them to their observed
      higher risk of suffering SPI while carrying loads.

PMID- 27884192
TI  - Role of cytochrome c in alpha-synuclein radical formation: implications of alpha
      synuclein in neuronal death in Maneb- and paraquat-induced model of Parkinson's
      disease.
AB  - BACKGROUND: The pathological features of Parkinson's disease (PD) include an
      abnormal accumulation of alpha-synuclein in the surviving dopaminergic neurons.
      Though PD is multifactorial, several epidemiological reports show an increased
      incidence of PD with co-exposure to pesticides such as Maneb and paraquat (MP).
      In pesticide-related PD, mitochondrial dysfunction and alpha-synuclein oligomers
      have been strongly implicated, but the link between the two has not yet been
      understood. Similarly, the biological effects of alpha-synuclein or its radical
      chemistry in PD is largely unknown. Mitochondrial dysfunction during PD
      pathogenesis leads to release of cytochrome c in the cytosol. Once in the
      cytosol, cytochrome c has one of two fates: It either binds to apaf1 and
      initiates apoptosis or can act as a peroxidase. We hypothesized that as a
      peroxidase, cytochrome c leaked out from mitochondria can form radicals on alpha
      synuclein and initiate its oligomerization. METHOD: Samples from controls, and MP
      co-exposed wild-type and alpha-synuclein knockout mice were studied using immuno
      spin trapping, confocal microscopy, immunohistochemistry, and microarray
      experiments. RESULTS: Experiments with MP co-exposed mice showed cytochrome c
      release in cytosol and its co-localization with alpha-synuclein. Subsequently, we
      used immuno-spin trapping method to detect the formation of alpha-synuclein
      radical in samples from an in vitro reaction mixture consisting of cytochrome c,
      alpha-synuclein, and hydrogen peroxide. These experiments indicated that
      cytochrome c plays a role in alpha-synuclein radical formation and
      oligomerization. Experiments with MP co-exposed alpha-synuclein knockout mice, in
      which cytochrome c-alpha synuclein co-localization and interaction cannot occur,
      mice showed diminished protein radical formation and neuronal death, compared to
      wild-type MP co-exposed mice. Microarray data from MP co-exposed wild-type and
      alpha-synuclein knockout mice further showed that the absence of alpha-synuclein
      per se or its co-localization with cytochrome c confers protection from MP co
      exposure, as several important pathways were unaffected in alpha-synuclein
      knockout mice. CONCLUSIONS: Altogether, these results show that peroxidase
      activity of cytochrome c contributes to alpha-synuclein radical formation and
      oligomerization, and that alpha-synuclein, through its co-localization with
      cytochrome c or on its own, affects several biological pathways which contribute
      to increased neuronal death in an MP-induced model of PD.

PMID- 27884188
TI  - Dietary patterns are associated with lung function among Spanish smokers without
      respiratory disease.
AB  - BACKGROUND: Diet can help preserve lung function in smokers, in addition to
      avoidance of smoking. The study aimed to evaluate associations between dietary
      patterns and lung function in smokers without respiratory disease. METHODS: This
      cross-sectional study analysed baseline data from randomised representative
      smokers without respiratory disease (n = 207, aged 35-70 years), selected from 20
      primary health-care centres. Participants completed a validated semi-quantitative
      food-frequency questionnaire. Dietary patterns were identified by Principal
      Component Analysis (PCA). Impaired lung function was defined as FVC <80% and/or
      FEV1 < 80% of predicted value and/or FEV1/FVC <0.7. Associations were determined
      by logistic regression. RESULTS: Three major dietary patterns were identified. In
      multivariate-adjusted model, impaired lung function was associated with the
      Alcohol-consumption pattern (OR 4.56, 95% CI 1.58-13.18), especially in women (OR
      11.47, 95% CI 2.25-58.47), and with the Westernised pattern in women (OR 5.62,
      95% CI 1.17-27.02), whereas it not was associated with the Mediterranean-like
      pattern (OR 0.71, 95% CI 0.28-1.79). CONCLUSION: In smokers without respiratory
      disease, the Alcohol-consumption pattern and the Westernised pattern are
      associated with impaired lung function, especially in women. The Mediterranean
      like pattern appears to be associated with preserved lung function because no
      statistical association is observed with impaired lung function. In addition to
      smoking cessation, modifying dietary patterns has possible clinical application
      to preserve lung function.

PMID- 27884193
TI  - Reorganising specialist cancer surgery for the twenty-first century: a mixed
      methods evaluation (RESPECT-21).
AB  - BACKGROUND: There are longstanding recommendations to centralise specialist
      healthcare services, citing the potential to reduce variations in care and
      improve patient outcomes. Current activity to centralise specialist cancer
      surgical services in two areas of England provides an opportunity to study the
      planning, implementation and outcomes of such changes. London Cancer and
      Manchester Cancer are centralising specialist surgical pathways for prostate,
      bladder, renal, and oesophago-gastric cancers, so that these services are
      provided in fewer hospitals. The centralisations in London were implemented
      between November 2015 and April 2016, while implementation in Manchester is
      anticipated in 2017. METHODS/DESIGN: This mixed methods evaluation will analyse
      stakeholder preferences for centralisations; it will use qualitative methods to
      analyse planning, implementation and sustainability of the centralisations ('how
      and why?'); and it will use a controlled before and after design to study the
      impact of centralisation on clinical processes, clinical outcomes, cost
      effectiveness and patient experience ('what works and at what cost?'). The study
      will use a framework developed in previous research on major system change in
      acute stroke services. A discrete choice experiment will examine patient, public
      and professional preferences for centralisations of this kind. Qualitative
      methods will include documentary analysis, stakeholder interviews and non
      participant observations of meetings. Quantitative methods will include analysis
      of local and national data on clinical processes, outcomes, costs and National
      Cancer Patient Experience Survey data. Finally, we will hold a workshop for those
      involved in centralisations of specialist services in other settings to discuss
      how these lessons might apply more widely. DISCUSSION: This multi-site study will
      address gaps in the evidence on stakeholder preferences for centralisations of
      specialist cancer surgery and the processes, impact and cost-effectiveness of
      changes of this kind. With increasing drives to centralise specialist services,
      lessons from this study will be of value to those who commission, organise and
      manage cancer services, as well as services for other conditions and in other
      settings. The study will face challenges in terms of recruitment, the
      retrospective analysis of some of the changes, the distinction between primary
      and secondary outcome measures, and obtaining information on the resources spent
      on the reconfiguration.

PMID- 27884194
TI  - Global health education in Germany: an analysis of current capacity, needs and
      barriers.
AB  - BACKGROUND: In times of increasing global challenges to health, it is crucial to
      create a workforce capable of tackling these complex issues. Even though a lack
      of GHE in Germany is perceived by multiple stakeholders, no systematic analysis
      of the current landscape exists. The aim of this study is to provide an analysis
      of the global health education (GHE) capacity in Germany as well as to identify
      gaps, barriers and future strategies. METHODS: An online search in combination
      with information provided by student representatives, course coordinators and
      lecturers was used to create an overview of the current GHE landscape in Germany.
      Additionally, a semi-structured questionnaire was sent to GHE educators and
      students engaged in global health (GH) to assess the capacity of German GHE, its
      barriers and suggested strategies for the future. RESULTS: A total of 33 GHE
      activities were identified at 18 German universities. Even though medical schools
      are the main provider of GHE (42%), out of 38 medical schools, only 13 (34%)
      offer any kind of GHE. Modules offered for students of other health-related
      professions constitute 27% of all activities. Most survey respondents (92%, n =
      48) consider current GHE activities in Germany insufficient. Suggested formats
      were GHE as part of medical curricula (82%, n = 45) and dual degree MD/MPH or PhD
      programs. Most important barriers mentioned were low priority of GH at faculties
      and academic management levels (n = 41, 75%) as well as lack of necessary
      institutional structures (n = 33, 60%). CONCLUSIONS: Despite some innovative
      academic approaches, there is clearly a need for more systematic GHE in Germany.
      GHE educators and students can take an important role advocating for more
      awareness at university management level and suggesting ways to institutionalize
      GHE to overcome barriers. This study provides key evidence, relevant perceptions
      and suggestions to strengthen GHE in Germany.

PMID- 27884195
TI  - Lymph node ratio as a prognostic factor in patients with pathological N2 non
      small cell lung cancer.
AB  - BACKGROUND: The aim of this study was to investigate whether the lymph node ratio
      (LNR) was associated with the prognosis of patients, who underwent surgery for
      pathological N2 non-small cell lung cancer (NSCLC). METHODS: A total of 182
      patients were diagnosed with pathological N2 disease and underwent complete
      resection surgeries with systematic lymphadenectomies. We counted the number of
      positives and removed lymph nodes to calculate a ratio between them (LNR). We
      also investigated the association between skip mediastinal lymph node metastasis
      and survival. RESULTS: Univariate analysis of survival in patients with N2 NSCLC
      showed that the T factor, clinical N factor, and LNR were significant prognostic
      factors. Multivariate analyses showed that the clinical N stage and LNR were
      significant independent prognostic factors for patients with pathological N2
      NSCLC. Patients with a clinical lymph node status of 0 (cN0) and LNR <=0.22
      showed a significantly higher survival rate than patients with a cN1-2 and LNR
      >=0.22 and 5-year survival rates were 47.1 and 10.3%, respectively (p < 0.0001).
      CONCLUSIONS: LNR is an important prognostic factor for poor outcome following
      surgery in patients with N2 disease. The combination of the LNR and cN status
      provides a valuable prognostic tool.

PMID- 27884196
TI  - Palliative treatment of pelvic bone tumors using radioiodine (125I)
      brachytherapy.
AB  - BACKGROUND: Complete resection of pelvic bone tumors, especially recurrent and
      metastatic ones, is often impossible to achieve using conventional surgery. This
      study aimed to assess the benefits and adverse effects of computed tomography
      (CT)-guided radioiodine (125I) brachytherapy for inoperable recurrent and
      metastatic bone tumors of the pelvis. METHODS: This was a retrospective study of
      22 patients with confirmed pelvic bone tumors (10 females and 12 males; 15-84
      years; 21 with primary pelvic tumor and one with pelvic metastasis). CT-guided
      125I brachytherapy was performed using 9-21 125I seeds (radioactivity of 0.5-0.7
      mCi). Seed implantation was validated by postoperative CT scanning.
      Complications, pain, survival, and CT-estimated tumor size were carried out to
      evaluate the therapeutic benefits. RESULTS: Postoperative CT scans revealed
      satisfactory 125I seed implantation, and the radiation dose delivered to 90% of
      the target area (D90) was higher than the prescription dose (PD). No obvious
      complications were observed. Pain was reported by 19 of 22 patients, but 17
      reported pain relief after implantation. Follow-up ranged 8-27 (median, 19)
      months. Tumor size was reduced in 11 patients within 1 month after surgery, nine
      patients showed no change, and tumor size increased in two patients. Finally, 1-
      and 2-year survival was 81.8 and 45.5%, respectively; 1- and 2-year local tumor
      control rates were 59.1 and 36.4%, respectively. CONCLUSIONS: 125I seed
      implantation significantly reduced bone tumor size and relieved pain, with a low
      complication rate. These findings suggest that 125I brachytherapy treatment could
      be a useful palliative approach for pelvic bone tumor treatment.

PMID- 27884197
TI  - Molecular survey and characterization of a novel Anaplasma species closely
      related to Anaplasma capra in ticks, northwestern China.
AB  - BACKGROUND: Anaplasma spp. are tick-transmitted bacteria that infect a wide
      variety of wild and domestic animals. These pathogens exhibit a high degree of
      biological diversity, broad geographical distribution, and represent a serious
      threat to veterinary and public health worldwide. RESULTS: A novel Anaplasma
      species was identified in Haemaphysalis qinghaiensis (Ixodidae) in northwestern
      China and was molecularly characterized by comparison of 16S rRNA, gltA, and
      groEL gene sequences. Of the 414 samples tested, 24 (5.8%) were positive for this
      Anaplasma species. On the basis of the 16S rRNA gene, this organism has been
      found to be closely related to and exhibit the highest sequence similarity with
      A. capra (99.8-99.9%) that was identified in goats and humans in northern China,
      but was distinct from other known Anaplasma species. Sequence analysis of the
      gltA and groEL genes revealed that this Anaplasma species was distinct from A.
      capra considering the lower sequence identity (88.6-88.7% for gltA and 90.6-91.0%
      for groEL) and a divergent phylogenetic position. Therefore, we described this
      Anaplasma species as A. capra-like bacteria. CONCLUSIONS: The present study
      reports a potential novel Anaplasma species closely related to A. capra in H.
      qinghaiensis in northwestern China. The zoonotic potential of A. capra-like
      bacteria needs to be further determined.

PMID- 27884200
TI  - A three-stage procedure using bone transportation for the treatment of
      sternoclavicular infectious arthritis.
AB  - BACKGROUND: Sternoclavicular joint (SCJ) infectious arthritis is a rare disease.
      A standard treatment for SCJ infection has not been established. This study aimed
      to assess the clinical outcomes of a three-stage procedure with bone
      transportation (BT) for treating SCJ infectious arthritis. METHODS: Six patients
      (mean age 39.5 years) with chronic SCJ infectious arthritis were included in the
      study. The patients underwent a three-stage treatment between January 2009 and
      December 2012, and results were analyzed retrospectively. Following debridement,
      immediate flap closure was conducted, and BT of the clavicle was performed to
      fill the gap using a monolateral external fixator. SCJ reconstruction with a
      tendon autograft was performed, and the external fixator was finally removed.
      Clinical outcomes were evaluated using Disabilities of the Arm, Shoulder, and
      Hand (DASH) scores and Constant scores. The average follow-up period was 16
      months (range 12-36 months). RESULTS: The DASH scores decreased from 53.6 +/- 4.9
      preoperatively to 24.4 +/- 3.1 postoperatively. The Constant scores for pain,
      activity level, positioning, strength, and range of motion were significantly
      high after the treatment. The total Constant score improved from 32.5 +/- 5.8
      preoperatively to 76.7 +/- 6.4 postoperatively. All patients were satisfied with
      the therapeutic effect. No complications occurred. CONCLUSIONS: The three-stage
      procedure with BT improves shoulder function and movement and relieves pain. It
      is an effective and safe method for treating SCJ infectious arthritis.

PMID- 27884199
TI  - A bibliometric analysis of literature on malaria vector resistance: (1996 -
      2015).
AB  - BACKGROUND: Emergence of insecticide resistance in malaria vectors is a real
      threat to future goals of elimination and control of malaria. Therefore, the
      objective of this study was to assess research trend on insecticide resistance of
      Anopheles mosquito. In specific, number of publications, countries, institutions,
      and authors' research profile, citation analysis, international collaborations,
      and impact of journals publishing documents on insecticide resistance will be
      presented. It was conducted via Scopus search engine which was used to retrieve
      relevant data. Keywords used were based on literature available on this topic.
      The duration of study was set from 1996-2015. RESULTS: A total of 616 documents,
      mainly as original research articles (n = 569; 92.37%) were retrieved. The
      average number of citations per article was 26.36. Poisson log-linear regression
      analysis indicated that there was a 6.00% increase in the number of publications
      for each extra article on pyrethroid resistance. A total of 82 different
      countries and 1922 authors participated in publishing retrieved articles. The
      United Kingdom (UK) ranked first in number of publications followed by the United
      States of America (USA) and France. The top ten productive countries included
      seven African countries. The UK had collaborations mostly with Benin (relative
      link strength = 46). A total of 1817 institution/ organizations participated in
      the publication of retrieved articles. The most active institution/ organization
      was Liverpool School of Tropical Medicine. Retrieved articles were published in
      134 different scientific peer reviewed journals. The journal that published most
      on this topic was Malaria Journal (n = 101; 16.4%). Four of the top active
      authors were from South Africa and two were from the UK. Three of the top ten
      cited articles were published in Insect Molecular Biology journal. Six articles
      were about pyrethroid resistance and at least two were about DDT resistance.
      CONCLUSION: Publications on insecticide resistance in malaria vector has gained
      momentum in the past decade. International collaborations enhanced the knowledge
      about the situation of vector resistance in countries with endemic malaria.
      Molecular biology of insecticide resistance is the key issue in understanding and
      overcoming this emerging problems.

PMID- 27884198
TI  - Use of poly ADP-ribose polymerase [PARP] inhibitors in cancer cells bearing DDR
      defects: the rationale for their inclusion in the clinic.
AB  - BACKGROUND: DNA damage response (DDR) defects imply genomic instability and favor
      tumor progression but make the cells vulnerable to the pharmacological inhibition
      of the DNA repairing enzymes. Targeting cellular proteins like PARPs, which
      cooperate and complement molecular defects of the DDR process, induces a specific
      lethality in DDR defective cancer cells and represents an anti-cancer strategy.
      Normal cells can tolerate the DNA damage generated by PARP inhibition because of
      an efficient homologous recombination mechanism (HR); in contrast, cancer cells
      with a deficient HR are unable to manage the DSBs and appear especially sensitive
      to the PARP inhibitors (PARPi) effects. MAIN BODY: In this review we discuss the
      proof of concept for the use of PARPi in different cancer types and the success
      and failure of their inclusion in clinical trials. The PARP inhibitor Olaparib
      [AZD2281] has been approved by the FDA for use in pretreated ovarian cancer
      patients with defective BRCA1/2 genes, and by the EMEA for maintenance therapy in
      platinum sensitive ovarian cancer patients with defective BRCA1/2 genes. BRCA
      mutations are now recognised as the molecular targets for PARPi sensitivity in
      several tumors. However, it is noteworthy that the use of PARPi has shown its
      efficacy also in non-BRCA related tumors. Several trials are ongoing to test
      different PARPi in different cancer types. Here we review the concept of BRCAness
      and the functional loss of proteins involved in DDR/HR mechanisms in cancer,
      including additional molecules that can influence the cancer cells sensitivity to
      PARPi. Given the complexity of the existing crosstalk between different DNA
      repair pathways, it is likely that a single biomarker may not be sufficient to
      predict the benefit of PARP inhibitors therapies. Novel general assays able to
      predict the DDR/HR proficiency in cancer cells and the PARPi sensitivity
      represent a challenge for a personalized therapy. CONCLUSIONS: PARP inhibition is
      a potentially important strategy for managing a significant subset of tumors. The
      discovery of both germline and somatic DNA repair deficiencies in different
      cancer patients, together with the development of new PARP inhibitors that can
      kill selectively cancer cells is a potent example of targeting therapy to
      molecularly defined tumor subtypes.

PMID- 27884201
TI  - Nickel pyrithione induces apoptosis in chronic myeloid leukemia cells resistant
      to imatinib via both Bcr/Abl-dependent and Bcr/Abl-independent mechanisms.
AB  - BACKGROUND: Acquired imatinib (IM) resistance is frequently characterized by Bcr
      Abl mutations that affect IM binding and kinase inhibition in patients with
      chronic myelogenous leukemia (CML). Bcr-Abl-T315I mutation is the predominant
      mechanism of the acquired resistance to IM. Therefore, it is urgent to search for
      additional approaches and targeting strategies to overcome IM resistance. We
      recently reported that nickel pyrithione (NiPT) potently inhibits the ubiquitin
      proteasome system via targeting the 19S proteasome-associated deubiquitinases
      (UCHL5 and USP14), without effecting on the 20S proteasome. In this present
      study, we investigated the effect of NiPT, a novel proteasomal deubiquitinase
      inhibitor, on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or
      wild-type Bcr-Abl. METHODS: Cell viability was examined by MTS assay and trypan
      blue exclusion staining assay in KBM5, KBM5R, K562, BaF3-p210-WT, BaF3-p210-T315I
      cells, and CML patients' bone marrow samples treated with NiPT. Cell apoptosis in
      CML cells was detected with Annexin V-FITC/PI and rhodamine-123 staining followed
      by fluorescence microscopy and flow cytometry and with western blot analyses for
      apoptosis-associated proteins. Expression levels of Bcr-Abl in CML cells were
      analyzed by using western blotting and real-time PCR. The 20S proteasome
      peptidase activity was measured using specific fluorogenic substrate. Active-site
      directed labeling of proteasomal DUBs, as well as the phosphorylation of USP14
      was used for evaluating the inhibition of the DUBs activity by NiPT. Mouse
      xenograft models of KBM5 and KBM5R cells were analyzed, and Bcr-Abl-related
      proteins and protein biomarkers related to proliferation, differentiation, and
      adhesion in tumor tissues were detected by western blots and/or
      immunohistological analyses. RESULTS: NiPT induced apoptosis in CML cells and
      inhibited the growth of IM-resistant Bcr-Abl-T315I xenografts in nude mice.
      Mechanistically, NiPT induced decreases in Bcr-Abl proteins, which were
      associated with downregulation of Bcr-Abl transcription and with the cleavage of
      Bcr-Abl protein by activated caspases. NiPT-induced ubiquitin proteasome system
      inhibition induced caspase activation in both IM-resistant and IM-sensitive CML
      cells, and the caspase activation was required for NiPT-induced Bcr-Abl
      downregulation and apoptotic cell death. CONCLUSIONS: These findings support that
      NiPT can overcome IM resistance through both Bcr-Abl-dependent and Bcr-Abl
      independent mechanisms, providing potentially a new option for CML treatment.

PMID- 27884202
TI  - Extending colonic mucosal microbiome analysis-assessment of colonic lavage as a
      proxy for endoscopic colonic biopsies.
AB  - BACKGROUND: Sequencing-based analysis has become a well-established approach to
      deciphering the composition of the gut microbiota. However, due to the complexity
      of accessing sufficient material from colonoscopic biopsy samples, most studies
      have focused on faecal microbiota analysis, even though it is recognised that
      differences exist between the microbial composition of colonic biopsies and
      faecal samples. We determined the suitability of colonic lavage samples to see if
      it had comparable microbial diversity composition to colonic biopsies as they are
      without the limitations associated with sample size. We collected paired colonic
      biopsies and lavage samples from subjects who were attending for colorectal
      cancer screening colonoscopy. RESULTS: Next-generation sequencing and qPCR
      validation were performed with multiple bioinformatics analyses to determine the
      composition and predict function of the microbiota. Colonic lavage samples
      contained significantly higher numbers of operational taxonomic units (OTUs)
      compared to corresponding biopsy samples, however, diversity and evenness between
      lavage and biopsy samples were similar. The differences seen were driven by the
      presence of 12 OTUs which were in higher relative abundance in biopsies and were
      either not present or in low relative abundance in lavage samples, whilst a
      further 3 OTUs were present in higher amounts in the lavage samples compared to
      biopsy samples. However, predicted functional community profiling based on 16S
      ribosomal ribonucleic acid (rRNA) data indicated minimal differences between
      sample types. CONCLUSIONS: We propose that colonic lavage samples provide a
      relatively accurate representation of biopsy microbiota composition and should be
      considered where biopsy size is an issue.

PMID- 27884203
TI  - A system dynamics model of clinical decision thresholds for the detection of
      developmental-behavioral disorders.
AB  - BACKGROUND: Clinical decision-making has been conceptualized as a sequence of two
      separate processes: assessment of patients' functioning and application of a
      decision threshold to determine whether the evidence is sufficient to justify a
      given decision. A range of factors, including use of evidence-based screening
      instruments, has the potential to influence either or both processes. However,
      implementation studies seldom specify or assess the mechanism by which screening
      is hypothesized to influence clinical decision-making, thus limiting their
      ability to address unexpected findings regarding clinicians' behavior. Building
      on prior theory and empirical evidence, we created a system dynamics (SD) model
      of how physicians' clinical decisions are influenced by their assessments of
      patients and by factors that may influence decision thresholds, such as knowledge
      of past patient outcomes. Using developmental-behavioral disorders as a case
      example, we then explore how referral decisions may be influenced by changes in
      context. Specifically, we compare predictions from the SD model to published
      implementation trials of evidence-based screening to understand physicians'
      management of positive screening results and changes in referral rates. We also
      conduct virtual experiments regarding the influence of a variety of interventions
      that may influence physicians' thresholds, including improved access to co
      located mental health care and improved feedback systems regarding patient
      outcomes. RESULTS: Results of the SD model were consistent with recent
      implementation trials. For example, the SD model suggests that if screening
      improves physicians' accuracy of assessment without also influencing decision
      thresholds, then a significant proportion of children with positive screens will
      not be referred and the effect of screening implementation on referral rates will
      be modest-results that are consistent with a large proportion of published
      screening trials. Consistent with prior theory, virtual experiments suggest that
      physicians' decision thresholds can be influenced and detection of disabilities
      improved by increasing access to referral sources and enhancing feedback
      regarding false negative cases. CONCLUSIONS: The SD model of clinical decision
      making offers a theoretically based framework to improve understanding of
      physicians' behavior and the results of screening implementation trials. The SD
      model is also useful for initial testing of hypothesized strategies to increase
      detection of under-identified medical conditions.

PMID- 27884204
TI  - Lateral pelvic lymph node dissection after neoadjuvant chemo-radiation for
      preoperative enlarged lateral nodes in advanced low rectal cancer: study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Lateral lymph node (LLN) metastasis is a major cause of local
      recurrence of advanced rectal cancer. Although there is much controversy between
      Western and Eastern countries on whether lateral pelvic lymph node dissection
      (LLND) or neoadjuvant chemo-radiation (nCRT) is preferable for the treatment of
      LLN metastases, existing retrospective cohorts mainly focus on all middle/low
      advanced rectal cancer patients, not the specific individuals with suspicion of
      LLN metastases. The aim of this trial is to assess the efficacy and safety of
      LLND for rectal cancer patients with suspicion of LLN metastases. METHODS: This
      prospective, multicenter, randomized controlled, single-blinded, phase III trial
      is designed to enroll 512 eligible patients with advanced rectal cancer and
      preoperative enlarged lateral lymph nodes. The population will be randomly
      assigned into the solely total mesorectal excision (TME) group or the TME + LLND
      group after eligible selection. The primary outcomes are to be 3-year local
      recurrence rate and 3-year disease-free survival, and the secondary outcomes
      include 3-year overall survival, 1-year sexual and urinary function, and
      perioperative outcomes. DISCUSSION: This is the first randomized trial to
      investigate the efficacy and safety of LLND for advanced low rectal cancer
      patients with suspicion of LLN metastases; the result is expected to provide new
      evidence for the treatment of LLN where there is suspicion of metastases in
      advanced rectal cancer patients. TRIAL REGISTRATION: This trial was registered at
      ClinicalTrials.gov (identifier NCT02614157 ) Registered on 24 November 2015.

PMID- 27884205
TI  - Whole genome sequence analysis of serum amino acid levels.
AB  - BACKGROUND: Blood levels of amino acids are important biomarkers of disease and
      are influenced by synthesis, protein degradation, and gene-environment
      interactions. Whole genome sequence analysis of amino acid levels may establish a
      paradigm for analyzing quantitative risk factors. RESULTS: In a discovery cohort
      of 1872 African Americans and a replication cohort of 1552 European Americans we
      sequenced exons and whole genomes and measured serum levels of 70 amino acids.
      Rare and low-frequency variants (minor allele frequency <=5%) were analyzed by
      three types of aggregating motifs defined by gene exons, regulatory regions, or
      genome-wide sliding windows. Common variants (minor allele frequency >5%) were
      analyzed individually. Over all four analysis strategies, 14 gene-amino acid
      associations were identified and replicated. The 14 loci accounted for an average
      of 1.8% of the variance in amino acid levels, which ranged from 0.4 to 9.7%.
      Among the identified locus-amino acid pairs, four are novel and six have been
      reported to underlie known Mendelian conditions. These results suggest that there
      may be substantial genetic effects on amino acid levels in the general population
      that may underlie inborn errors of metabolism. We also identify a predicted
      promoter variant in AGA (the gene that encodes aspartylglucosaminidase) that is
      significantly associated with asparagine levels, with an effect that is
      independent of any observed coding variants. CONCLUSIONS: These data provide
      insights into genetic influences on circulating amino acid levels by integrating 
      omic technologies in a multi-ethnic population. The results also help establish a
      paradigm for whole genome sequence analysis of quantitative traits.

PMID- 27884206
TI  - Large-scale benchmarking reveals false discoveries and count transformation
      sensitivity in 16S rRNA gene amplicon data analysis methods used in microbiome
      studies.
AB  - BACKGROUND: There is an immense scientific interest in the human microbiome and
      its effects on human physiology, health, and disease. A common approach for
      examining bacterial communities is high-throughput sequencing of 16S rRNA gene
      hypervariable regions, aggregating sequence-similar amplicons into operational
      taxonomic units (OTUs). Strategies for detecting differential relative abundance
      of OTUs between sample conditions include classical statistical approaches as
      well as a plethora of newer methods, many borrowing from the related field of RNA
      seq analysis. This effort is complicated by unique data characteristics,
      including sparsity, sequencing depth variation, and nonconformity of read counts
      to theoretical distributions, which is often exacerbated by exploratory and/or
      unbalanced study designs. Here, we assess the robustness of available methods for
      (1) inference in differential relative abundance analysis and (2) beta-diversity
      based sample separation, using a rigorous benchmarking framework based on large
      clinical 16S microbiome datasets from different sources. RESULTS: Running more
      than 380,000 full differential relative abundance tests on real datasets with
      permuted case/control assignments and in silico-spiked OTUs, we identify large
      differences in method performance on a range of parameters, including false
      positive rates, sensitivity to sparsity and case/control balances, and spike-in
      retrieval rate. In large datasets, methods with the highest false positive rates
      also tend to have the best detection power. For beta-diversity-based sample
      separation, we show that library size normalization has very little effect and
      that the distance metric is the most important factor in terms of separation
      power. CONCLUSIONS: Our results, generalizable to datasets from different
      sequencing platforms, demonstrate how the choice of method considerably affects
      analysis outcome. Here, we give recommendations for tools that exhibit low false
      positive rates, have good retrieval power across effect sizes and case/control
      proportions, and have low sparsity bias. Result output from some commonly used
      methods should be interpreted with caution. We provide an easily extensible
      framework for benchmarking of new methods and future microbiome datasets.

PMID- 27884208
TI  - What are the best methodologies for rapid reviews of the research evidence for
      evidence-informed decision making in health policy and practice: a rapid review.
AB  - BACKGROUND: Rapid reviews have the potential to overcome a key barrier to the use
      of research evidence in decision making, namely that of the lack of timely and
      relevant research. This rapid review of systematic reviews and primary studies
      sought to answer the question: What are the best methodologies to enable a rapid
      review of research evidence for evidence-informed decision making in health
      policy and practice? METHODS: This rapid review utilised systematic review
      methods and was conducted according to a pre-defined protocol including clear
      inclusion criteria (PROSPERO registration: CRD42015015998). A comprehensive
      search strategy was used, including published and grey literature, written in
      English, French, Portuguese or Spanish, from 2004 onwards. Eleven databases and
      two websites were searched. Two review authors independently applied the
      eligibility criteria. Data extraction was done by one reviewer and checked by a
      second. The methodological quality of included studies was assessed independently
      by two reviewers. A narrative summary of the results is presented. RESULTS: Five
      systematic reviews and one randomised controlled trial (RCT) that investigated
      methodologies for rapid reviews met the inclusion criteria. None of the
      systematic reviews were of sufficient quality to allow firm conclusions to be
      made. Thus, the findings need to be treated with caution. There is no agreed
      definition of rapid reviews in the literature and no agreed methodology for
      conducting rapid reviews. While a wide range of 'shortcuts' are used to make
      rapid reviews faster than a full systematic review, the included studies found
      little empirical evidence of their impact on the conclusions of either rapid or
      systematic reviews. There is some evidence from the included RCT (that had a low
      risk of bias) that rapid reviews may improve clarity and accessibility of
      research evidence for decision makers. CONCLUSIONS: Greater care needs to be
      taken in improving the transparency of the methods used in rapid review products.
      There is no evidence available to suggest that rapid reviews should not be done
      or that they are misleading in any way. We offer an improved definition of rapid
      reviews to guide future research as well as clearer guidance for policy and
      practice.

PMID- 27884207
TI  - Potential contribution of the uterine microbiome in the development of
      endometrial cancer.
AB  - BACKGROUND: Endometrial cancer studies have led to a number of well-defined but
      mechanistically unconnected genetic and environmental risk factors. One of the
      emerging modulators between environmental triggers and genetic expression is the
      microbiome. We set out to inquire about the composition of the uterine microbiome
      and its putative role in endometrial cancer. METHODS: We undertook a study of the
      microbiome in samples taken from different locations along the female
      reproductive tract in patients with endometrial cancer (n = 17), patients with
      endometrial hyperplasia (endometrial cancer precursor, n = 4), and patients
      afflicted with benign uterine conditions (n = 10). Vaginal, cervical, Fallopian,
      ovarian, peritoneal, and urine samples were collected aseptically both in the
      operating room and the pathology laboratory. DNA extraction was followed by
      amplification and high-throughput next generation sequencing (MiSeq) of the 16S
      rDNA V3-V5 region to identify the microbiota present. Microbiota data were
      summarized using both alpha-diversity to reflect species richness and evenness
      within bacterial populations and beta-diversity to reflect the shared diversity
      between bacterial populations. Statistical significance was determined through
      the use of multiple testing, including the generalized mixed-effects model.
      RESULTS: The microbiome sequencing (16S rDNA V3-V5 region) revealed that the
      microbiomes of all organs (vagina, cervix, Fallopian tubes, and ovaries) are
      significantly correlated (p < 0.001) and that there is a structural microbiome
      shift in the cancer and hyperplasia cases, distinguishable from the benign cases
      (p = 0.01). Several taxa were found to be significantly enriched in samples
      belonging to the endometrial cancer cohort: Firmicutes (Anaerostipes, ph2,
      Dialister, Peptoniphilus, 1-68, Ruminococcus, and Anaerotruncus), Spirochaetes
      (Treponema), Actinobacteria (Atopobium), Bacteroidetes (Bacteroides and
      Porphyromonas), and Proteobacteria (Arthrospira). Of particular relevance, the
      simultaneous presence of Atopobium vaginae and an uncultured representative of
      the Porphyromonas sp. (99 % match to P. somerae) were found to be associated with
      disease status, especially if combined with a high vaginal pH (>4.5).
      CONCLUSIONS: Our results suggest that the detection of A. vaginae and the
      identified Porphyromonas sp. in the gynecologic tract combined with a high
      vaginal pH is statistically associated with the presence of endometrial cancer.
      Given the documented association of the identified microorganisms with other
      pathologies, these findings raise the possibility of a microbiome role in the
      manifestation, etiology, or progression of endometrial cancer that should be
      further investigated.

PMID- 27884210
TI  - Characteristics of illegal and legal cigarette packs sold in Guatemala.
AB  - BACKGROUND: Guatemala, as a party to the Framework Convention on Tobacco Control
      (FCTC), is required to regulate cigarette packaging and labeling and eliminate
      illicit tobacco trade. Current packaging and labeling characteristics (of legal
      and illegal cigarettes) and their compliance with the FCTC is unknown. METHODS:
      We sought to analyze package and label characteristics of illegal and legal
      cigarettes sold in Guatemala. We visited the 22 largest traditional markets in
      the country to purchase illegal cigarettes. All brands registered on tobacco
      industry websites were purchased as legal cigarettes. Analysis compared labeling
      characteristics of illegal and legal packs. FINDINGS: Most (95%) markets and
      street vendors sold illegal cigarettes; 104 packs were purchased (79 illegal and
      25 legal). Ten percent of illegal and none of the legal packs had misleading
      terms. Half of the illegal packs had a warning label covering 26 to 50% of the
      pack surface. All legal packs had a label covering 25% of the surface. Illegal
      packs were more likely to have information on constituents and emissions (85% vs.
      45%, p < 0.001) and were less expensive than legal ones (USD 0.70 +/- 0.7 and 1.9
      +/- 1.8, p < 0.001). CONCLUSIONS: In Guatemala, neither illegal nor legal
      cigarette packs comply with FCTC labeling mandates. Urgent implementation and
      enforcement of the FCTC is necessary to halt the tobacco epidemic.

PMID- 27884209
TI  - To each his own: no evidence of gyrodactylid parasite host switches from invasive
      poeciliid fishes to Goodea atripinnis Jordan (Cyprinodontiformes: Goodeidae), the
      most dominant endemic freshwater goodeid fish in the Mexican Highlands.
AB  - BACKGROUND: Goodeid topminnows are live-bearing fishes endemic to the Mexican
      Highlands (Mesa Central, MC). Unfortunately, in the MC, environmental degradation
      and introduced species have pushed several goodeid species to the brink of
      extinction. Invasive fishes can introduce exotic parasites, and the most abundant
      goodeid, blackfin goodea Goodea atripinnis Jordan, is parasitised by six exotic
      helminths. Poeciliids are widely dispersed invasive fishes, which exert negative
      ecological effects on goodeids. Poeciliids host several species of the monogenean
      genus Gyrodactylus von Nordmann, 1832, including pathogenic, invasive parasites.
      Here, we looked for evidence of Gyrodactylus species switching hosts from
      poeciliids to goodeids. METHODS: Fish were collected in rivers draining the MC
      into both sides of the continental divide. Hosts were screened for gyrodactylid
      parasites in localities where G. atripinnis and poeciliids occurred
      sympatrically. Gyrodactylus specimens were characterised morphologically
      (attachment apparatus) and molecularly (internal transcribed spacer region, ITS).
      A Bayesian phylogenetic tree using ITS sequences established relationships
      between gyrodactylids collected from goodeid fishes and those from parasites
      infecting poeciliids. RESULTS: Gyrodactylids were collected from G. atripinnis in
      six localities on both sides of the watershed where exotic poeciliids occurred
      sympatrically. Morphological and molecular analyses indicated the presence of
      four undescribed species of Gyrodactylus infecting this goodeid host.
      Gyrodactylus tomahuac n. sp., the most abundant and geographically widespread
      species, is described here. The other three Gyrodactylus spp. are not described,
      but their ITS sequences are used as molecular data presented here, are the only
      available for gyrodactylids infecting goodeid fishes. Morphological and molecular
      data suggest that two distinct groups of gyrodactylids infect goodeids, one of
      which shares a common ancestor with gyrodactylids parasitizing poeciliids.
      CONCLUSIONS: No evidence was found of gyrodactylids switching hosts from invasive
      poeciliids to endemic goodeids, nor vice versa. Moreover, considering that G.
      atripinnis is known to host both Gyrodactylus lamothei Mendoza-Palmero, Sereno
      Uribe & Salgado-Maldonado, 2009 and Gyrodactylus mexicanus Mendoza-Palmero,
      Sereno-Uribe & Salgado-Maldonado, 2009, with the addition of G. tomahuac n. sp.
      and the three undescribed Gyrodactylus spp. reported, at least six gyrodactylids
      may infect this host. This would make monogeneans the second most abundant
      parasite group infecting G. atripinnis, which to date is known to harbour 22
      helminth species: nine digeneans, five nematodes, four cestodes, three
      monogeneans and one acanthocephalan.

PMID- 27884211
TI  - Plasma glutamine levels before cardiac surgery are related to post-surgery
      infections; an observational study.
AB  - BACKGROUND: A low plasma glutamine level was found in 34% of patients after
      elective cardiothoracic surgery. This could be a result of the inflammation
      caused by surgical stress or the use of extracorporeal circulation (ECC). But it
      is also possible that plasma glutamine levels were already lowered before surgery
      and reflect an impaired metabolic state and a higher likelihood to develop
      complications. In the present study plasma glutamine levels were measured before
      and after cardiac surgery and we questioned whether there is a relation between
      plasma glutamine levels and duration of ECC and the occurrence of postoperative
      infections. METHODS: We performed a single-centre prospective, observational
      study in a closed-format, 20-bed, mixed ICU in a tertiary teaching hospital. We
      included consecutive patients after elective cardiac surgery with use of
      extracorporeal circulation. Blood samples were collected on the day prior to
      surgery and at admission on the ICU. The study was approved by the local Medical
      Ethics Committee (Regional Review Committee Patient-related Research, Medical
      Centre Leeuwarden, nWMO 115, April 28th 2015). RESULTS: Ninety patients were
      included. Pre-operative plasma glutamine level was 0.42 +/- 0.10 mmol/l and post
      operative 0.38 +/- 0.09 mmol/l (p < 0.001). There was no relation between
      duration of extracorporeal circulation or aortic occlusion time and changes in
      plasma glutamine levels. A logistic regression analysis showed a significant
      correlation between the presence of a positive culture during the post-operative
      course and pre-operative plasma glutamine levels (p = 0.04). CONCLUSION: Plasma
      glutamine levels are significantly lower just after cardiac surgery compared to
      pre-operative levels. We did not find a relation between the decrease in plasma
      glutamine levels and the duration of extracorporeal circulation or aortic clamp
      time. There was a correlation between pre-operative plasma glutamine levels and
      the presence of a positive culture after cardiac surgery. TRIAL REGISTRATION:
      ClinicalTrials.gov, number NCT02444780 .

PMID- 27884213
TI  - Regional variation in Ascaris lumbricoides and Trichuris trichiura infections by
      age cohort and sex: effects of market integration among the indigenous Shuar of
      Amazonian Ecuador.
AB  - BACKGROUND: Soil-transmitted helminth (STH) infection peaks during childhood and
      varies by sex. The impact of market integration (MI) (increasing production for
      and consumption from a market-based economy) on these infection patterns,
      however, is unclear. In this study, STH infection is examined by sex and age
      among indigenous Shuar inhabiting two regions of Amazonian Ecuador: (1) the
      modestly market-integrated Upano Valley (UV) and (2) the more traditional Cross
      Cutucu (CC) region. METHODS: Kato-Katz fecal smears were examined for parasite
      presence and infection intensity. Factorial ANOVAs and post hoc simple effects
      analyses were performed by sex to compare infection intensity between regions and
      age categories (infant/child, juvenile/adolescent, adult). RESULTS: Significant
      age and regional differences in Ascaris lumbricoides and Trichuris trichiura
      infection were detected. Overall, infants/children and juveniles/adolescents
      displayed higher parasite loads than adults. CC females exhibited higher A.
      lumbricoides loads than UV females, while the opposite pattern was observed for
      T. trichiura infection in males. CONCLUSIONS: Regional infection patterns varied
      by sex and parasite species, perhaps due to MI-linked environmental and lifestyle
      changes. These results have public health implications for the identification of
      individuals at risk for infection and contribute to ongoing efforts to track
      changes and alleviate STH infection in indigenous populations undergoing MI.

PMID- 27884212
TI  - Angiotensin-converting enzyme 2 is reduced in Alzheimer's disease in association
      with increasing amyloid-beta and tau pathology.
AB  - BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system
      (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type
      1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer's disease (AD).
      Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1-7 (Ang  
      (1-7)) and counter-regulates the classical axis of RAS. We have investigated the
      expression and distribution of ACE-2 in post-mortem human brain tissue in
      relation to AD pathology and classical RAS axis activity. METHODS: We measured
      ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex
      (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented
      controls (n = 59) for which we have previous data on ACE-1 activity, amyloid beta
      (Abeta) level and tau pathology, as well as known ACE1 (rs1799752) indel
      polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy
      severity scores. RESULTS: ACE-2 activity was significantly reduced in AD compared
      with age-matched controls (P < 0.0001) and correlated inversely with levels of
      Abeta (r = -0.267, P < 0.001) and phosphorylated tau (p-tau) pathology (r = 
      0.327, P < 0.01). ACE-2 was reduced in individuals possessing an APOE epsilon4
      allele (P < 0.05) and was associated with ACE1 indel polymorphism (P < 0.05),
      with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD
      risk allele. ACE-2 activity correlated inversely with ACE-1 activity (r = -0.453,
      P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD (P
      < 0.0001). Finally, we show that the ratio of Ang II to Ang (1-7) (a proxy
      measure of ACE-2 activity indicating  conversion of Ang II to Ang (1-7)) is
      reduced in AD. CONCLUSIONS: Together, our findings indicate that ACE-2 activity
      is reduced in AD and is an important regulator of the central classical ACE-1/Ang
      II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a
      significant role in the pathogenesis of AD.

PMID- 27884216
TI  - Honour and subsistence: invention, credit and surgery in the nineteenth century.
AB  - The origins of contemporary exclusion of surgical methods from patenting lie in
      the complexities of managing credit claims in operative surgery, recognized in
      the nineteenth century. While surgical methods were not deemed patentable,
      surgeons were nevertheless embedded within patent culture. In an atmosphere of
      heightened awareness about the importance of 'inventors', how surgeons should be
      recognized and rewarded for their inventions was an important question. I examine
      an episode during the 1840s which seemed to concretize the inapplicability of
      patents to surgical practice, before looking at alternatives to patenting, used
      by surgeons to gain social and financial credit for inventions.

PMID- 27884215
TI  - Public Perception of Emergency Medical Services in the United States.
AB  - OBJECTIVE: The objective of this study was to assess the public's experience,
      expectations, and perceptions related to Emergency Medical Services (EMS).
      METHODS: A population-based telephone interview of adults in the United States
      was conducted. The survey instrument consisted of 112 items. Demographic
      variables including age, race, political beliefs, and household income were
      collected. Data collection was performed by trained interviewers from Kent State
      University's (Kent, Ohio USA)Social Research Laboratory. Descriptive statistics
      were calculated. Comparative analyses were conducted between those who used EMS
      at least once in the past five years and those who did not use EMS using chi2 and
      t tests. RESULTS: A total of 2,443 phone calls were made and 1,348 individuals
      agreed to complete the survey (55.2%). There were 297 individuals who requested
      to drop out of the survey during the phone interview, leaving a total of 1,051
      (43.0%) full responses. Participants ranged in age from 18 to 94 years with an
      average age of 57.5 years. Most were Caucasian or white (83.0%), married (62.8%),
      and held conservative political beliefs (54.8%). Three-fourths of all respondents
      believed that at least 40% of patients survive cardiac arrest when EMS services
      are received. Over half (56.7%) believed that Emergency Medical Technician (EMT)
      Basics and EMT-Paramedics provide the same level of care. The estimated median
      hours of training required for EMT-Basics was 100 hours (IQR: 40-200 hours),
      while the vast majority of respondents estimated that EMT-Paramedics are required
      to take fewer than 1,000 clock hours of training (99.3%). The majority believed
      EMS professionals should be screened for illegal drug use (97.0%), criminal
      background (95.9%), mental health (95.2%), and physical fitness (91.3%). Over one
      third (37.6%) had used EMS within the past five years. Of these individuals, over
      two-thirds (69.6%) rated their most recent experience as "excellent." More of
      those who used EMS at least once in the past five years reported a willingness to
      consent to participate in EMS research compared with those who had not used EMS
      (69.9% vs. 61.4%, P=.005). CONCLUSIONS: Most respondents who had used EMS
      services rated their experience as excellent. Nevertheless, expectations related
      to survival after cardiac arrest in the out-of-hospital setting were not
      realistic. Furthermore, much of the public was unaware of the differences in
      training hour requirements and level of care provided by EMT-Basics and EMT
      Paramedics. Crowe RP , Levine R , Rodriguez S , Larrimore AD , Pirrallo RG .
      Public perception of Emergency Medical Services in the United States. Prehosp
      Disaster Med. 2016;31(Suppl. 1):s112-s117.

PMID- 27884214
TI  - Neuronal and glial changes in the brain resulting from explosive blast in an
      experimental model.
AB  - Mild traumatic brain injury (mTBI) is the signature injury in warfighters exposed
      to explosive blasts. The pathology underlying mTBI is poorly understood, as this
      condition is rarely fatal and thus postmortem brains are difficult to obtain for
      neuropathological studies. Here we report on studies of an experimental model
      with a gyrencephalic brain that is exposed to single and multiple explosive blast
      pressure waves. To determine injuries to the brain resulting from the primary
      blast, experimental conditions were controlled to eliminate any secondary or
      tertiary injury from blasts. We found small but significant levels of neuronal
      loss in the hippocampus, a brain area that is important for cognitive functions.
      Furthermore, neuronal loss increased with multiple blasts and the degree of
      neuronal injury worsened with time post-blast. This is consistent with our
      findings in the blast-exposed human brain based on magnetic resonance
      spectroscopic imaging. The studies on this experimental model thus confirm what
      has been presumed to be the case with the warfighter, namely that exposure to
      multiple blasts causes increased brain injury. Additionally, as in other studies
      of both explosive blast as well as closed head mTBI, we found astrocyte
      activation. Activated microglia were also prominent in white matter tracts,
      particularly in animals exposed to multiple blasts and at long post-blast
      intervals, even though injured axons (i.e. beta-APP positive) were not found in
      these areas. Microglial activation appears to be a delayed response, though
      whether they may contribute to inflammation related injury mechanism at even
      longer post-blast times than we tested here, remains to be explored. Petechial
      hemorrhages or other gross signs of vascular injury were not observed in our
      study. These findings confirm the development of neuropathological changes due to
      blast exposure. The activation of astrocytes and microglia, cell types
      potentially involved in inflammatory processes, suggest an important area for
      future study.

PMID- 27884217
TI  - From neurocognition to community participation in serious mental illness: the
      intermediary role of dysfunctional attitudes and motivation.
AB  - BACKGROUND: Evidence for a relationship between neurocognition and functional
      outcome in important areas of community living is robust in serious mental
      illness research. Dysfunctional attitudes (defeatist performance beliefs and
      asocial beliefs) have been identified as intervening variables in this causal
      chain. This study seeks to expand upon previous research by longitudinally
      testing the link between neurocognition and community participation (i.e. time in
      community-based activity) through dysfunctional attitudes and motivation. METHOD:
      Adult outpatients with serious mental illness (N = 175) participated, completing
      follow-up assessments approximately 6 months after initial assessment. Path
      analysis tested relationships between baseline neurocognition, emotion
      perception, functional skills, dysfunctional attitudes, motivation, and outcome
      (i.e. community participation) at baseline and follow-up. RESULTS: Path models
      demonstrated two pathways to community participation. The first linked
      neurocognition and community participation through functional skills, defeatist
      performance beliefs, and motivation. A second pathway linked asocial beliefs and
      community participation, via a direct path passing through motivation. Model fit
      was excellent for models predicting overall community participation at baseline
      and, importantly, at follow-up. CONCLUSIONS: The existence of multiple pathways
      to community participation in a longitudinal model supports the utility of multi
      modal interventions for serious mental illness (i.e. treatment packages that
      build upon individuals' strengths while addressing the array of obstacles to
      recovery) that feature dysfunctional attitudes and motivation as treatment
      targets.

PMID- 27884218
TI  - The Current State of Perioperative Pain Management: Challenges and Potential
      Opportunities for Nurses.
AB  - Achievement of adequate postoperative pain management is a critical challenge in
      health care, with an estimated three out of four adult surgical patients
      reporting moderate to extreme pain after surgery. Overreliance on opioids in
      acute care settings has persisted, despite well-known adverse side effects
      frequently associated with this class of drugs. Furthermore, patients with a
      history of chronic opioid use present additional challenges in terms of
      postsurgical pain management. Advances in the development of newer analgesic
      agents and anesthetic techniques may be useful in surgical patients with a
      history of chronic opioid use and in the overall surgical patient population.
      Systemic inefficiencies and problematic medical practice patterns can also have
      negative effects on perioperative pain management. As the surgical patient's
      primary advocate, perioperative nurses play an important role in overcoming these
      diverse challenges and addressing the problems associated with inadequately
      controlled postsurgical pain.

PMID- 27884219
TI  - The Role of the Perioperative Nurse in Improving Surgical Patients' Clinical
      Outcomes and Satisfaction: Beyond Medication.
AB  - For the perioperative nurse, the management of postsurgical pain includes various
      responsibilities, such as performing postsurgical pain assessments as an
      essential first step, facilitating recovery from surgery, and maximizing patient
      satisfaction during the postsurgical period. In addition, nurses are responsible
      for providing patient education regarding pain management, the quality of which
      may strongly influence patient satisfaction. External and internal challenges
      exist in perioperative care processes, however, and addressing these challenges
      will promote the overall goal of providing high-quality care.

PMID- 27884221
TI  - Hypertension: New and Future Challenges.
AB  - This article provides a preview to the forthcoming articles in this issue, which
      are written by well-known and authoritative authors for the readers' pleasure and
      reference. This article hopes to provide a general overview that stimulates
      interest, better understanding, and continued joint commitment to the important
      subject of hypertension.

PMID- 27884220
TI  - Multimodal Pain Management for Enhanced Recovery: Reinforcing the Shift From
      Traditional Pathways Through Nurse-Led Interventions.
AB  - Despite recent advances in perioperative patient care, postsurgical pain
      continues to be undermanaged. There is increasing acceptance of the concept that
      effective postsurgical pain management is best achieved through combined use of
      more than one analgesic agent or technique, and overreliance on opioids produces
      unwanted side effects limiting their utility. Accordingly, a balanced, multimodal
      approach to pain management within the larger framework of an Enhanced Recovery
      After Surgery (ERAS) pathway has become standard at many institutions for
      perioperative care, to control postsurgical pain, reduce opioid-related adverse
      events, hasten postsurgical recovery, and shorten length of hospital stay. The
      success of ERAS is dependent on nurses and the multidisciplinary team to execute
      its standardized processes across the care continuum, including patient
      education, perioperative care, and postsurgical evaluation. Here, we review
      current concepts related to multimodal analgesia and ERAS regarding care of adult
      surgical patients and discuss the perioperative nurse's role within this
      paradigm.

PMID- 27884222
TI  - A Reassessment of the Pathophysiology of Progressive Cardiorenal Disorders.
AB  - Heart failure and chronic renal diseases are usually progressive and only
      partially amenable to therapy. These disorders can be the sequelae of
      hypertension or worsened by hypertension. They are associated with the tissue up
      regulation of multiple peptides, many of which are capable of acting within the
      cell interior. This article proposes that these peptides, intracrines, can form
      self-sustaining regulatory loops that can spread through heart or kidney,
      producing progressive disease. Moreover, mineralocorticoid activation seems
      capable of amplifying some of these peptide networks. This view suggests an
      expanded explanation of the pathogenesis of progressive cardiorenal disease and
      suggests new approaches to treatment.

PMID- 27884223
TI  - Local Renin Angiotensin Aldosterone Systems and Cardiovascular Diseases.
AB  - The presence of local renin angiotensin aldosterone systems (RAAS) in the
      cardiovascular and renal tissues and their influence in cardiovascular and renal
      diseases are described. The fundamental role of ACE/Ang II/AT1 receptor axis
      activation as well the counterregulatory role of ACE2/Ang (1-7)/Mas receptor
      activation on cardiovascular and renal physiology and pathology are emphasized.
      The presence of a local RAS and its influence on hypertension is discussed, and
      finally, the hypothesis that epigenetic factors change the RAAS in utero and
      induce the expression of renin or Ang II inside the cells of the cardiovascular
      system is presented.

PMID- 27884225
TI  - Obesity: A Perspective from Hypertension.
AB  - The prevalence of obesity-related hypertension is high worldwide and has become a
      major health issue. The mechanisms by which obesity relates to hypertensive
      disease are still under intense research scrutiny, and include altered
      hemodynamics, impaired sodium homeostasis, renal dysfunction, autonomic nervous
      system imbalance, endocrine alterations, oxidative stress and inflammation, and
      vascular injury. Most of these contributing factors interact with each other at
      multiple levels. Thus, as a multifactorial and complex disease, obesity-related
      hypertension should be recognized as a distinctive form of hypertension, and
      specific considerations should apply in planning therapeutic approaches to treat
      obese individuals with high blood pressure.

PMID- 27884224
TI  - The Renin Angiotensin Aldosterone System in Obesity and Hypertension: Roles in
      the Cardiorenal Metabolic Syndrome.
AB  - In the United States, more than 50 million people have blood pressure at or above
      120/80 mm Hg. All components of cardiorenal metabolic syndrome (CRS) are linked
      to metabolic abnormalities and obesity. A major driver for CRS is obesity.
      Current estimates show that many of those with hypertension and CRS show some
      degree of systemic and cardiovascular insulin resistance. Several
      pathophysiologic factors participate in the link between hypertension and CRS.
      This article updates recent literature with a focus on the function of insulin
      resistance, obesity, and renin angiotensin aldosterone system-mediated oxidative
      stress on endothelial dysfunction and the pathogenesis of hypertension.

PMID- 27884226
TI  - Patient Management of Hypertensive Subjects without and with Diabetes Mellitus
      Type II.
AB  - The description of blood pressure (BP) curve has evolved to include several
      noninvasively determined parameters, such as aortic stiffness, BP variability,
      wave reflections, and pulse pressure amplification. These techniques are likely
      to improve the efficacy of assessing pulsatile arterial hemodynamics and changes
      in arterial stiffness. The goal for future antihypertensive treatments should not
      only reduce steady BP, but also control pulsatile pressure and modify the
      stiffness gradient between central and peripheral arteries, which is frequently
      elevated. These changes have the potential to reduce residual cardiovascular risk
      but also to define drug strategies adapted to the needs of individual
      hypertensive subjects.

PMID- 27884228
TI  - Heart Failure and Hypertension: Importance of Prevention.
AB  - This article discusses the role of hypertension in heart failure. Elevated blood
      pressure has the greatest population attributable risk for the development of
      heart failure. The mortality rates following the clinical recognition of heart
      failure is increased multifold. The treatment of hypertension with
      antihypertensive agents is particularly effective in preventing heart failure,
      which makes it the most effective therapy for heart failure.

PMID- 27884229
TI  - What Have We Learned from the Genetics of Hypertension?
AB  - Twin studies show that about half the risk of hypertension development is
      inherited. Mendelian hypertension has elucidated astounding basic pathways
      contributing to hypertension over (presumably) dietary salt intake or directly
      through increased peripheral vascular resistance. The Mendelian mutations
      exercise large effects on blood pressure. Inversely, studying the entire human
      genome for sources signaling blood pressure has yielded many signals with small
      effects. Thus far, few loci have been validated or translated into targets. Both
      genetic strategies are necessary, and much remains to be done.

PMID- 27884230
TI  - The Kidney in Hypertension.
AB  - Hypertension is the second most common cause of chronic kidney disease (CKD) and
      is a potentiator of kidney failure when accompanying disease. CKD is a common
      cause of resistant hypertension. Nephropathy progression has dramatically slowed
      over the past 3 decades from an average of 8 to between 2-3 mL/min per year
      regardless of diabetes status. The incidence of very high albuminuria as well as
      progression from high albuminuria very high albuminuria has substantially
      decreased over the past 3 decades. This improvement relates to better blood
      pressure control using agents that slow nephropathy as well as better glycemic
      and cholesterol control.

PMID- 27884231
TI  - Guidelines for the Management of Hypertension.
AB  - This article summarizes pertinent data from clinical trials on the effects of
      antihypertensive therapy on cardiovascular complications. Prior definitions of
      hypertension and blood pressure goals of therapy are discussed, and differences
      between national and international guidelines on such goals are summarized. The
      results of the SPRINT study are summarized, and the impact of this study on
      future goals of treatment is discussed. New recommendations are provided on blood
      pressure goals, and the effects such goals might have on clinical practice are
      discussed.

PMID- 27884233
TI  - Hypertension, Left Ventricular Hypertrophy, and Myocardial Ischemia.
AB  - The risks associated with hypertension emerge through a series of complex
      interactions. Myocardial ischemia is the major contributor to this risk. The
      mechanisms driving ischemia reflect many of the key factors in hypertension,
      including endothelial and neurohumoral factors, fibrosis, and hemodynamics. Left
      ventricular hypertrophy and fibrosis are of fundamental importance and together
      with hemodynamics provide an optimal template for myocardial ischemia.
      Understanding the pathophysiology has aided a more rational management approach
      but challenges remain which, if surmounted, will have an impact on the morbidity
      and mortality caused by myocardial ischemia in patients with hypertension.

PMID- 27884227
TI  - Oxidative Stress and Hypertensive Diseases.
AB  - It has become clear that reactive oxygen species (ROS) contribute to the
      development of hypertension via myriad effects. ROS are essential for normal cell
      function; however, they mediate pathologic changes in the brain, the kidney, and
      blood vessels that contribute to the genesis of chronic hypertension. There is
      also emerging evidence that ROS contribute to immune activation in hypertension.
      This article discusses these events and how they coordinate to contribute to
      hypertension and its consequent end-organ damage.

PMID- 27884234
TI  - The Hypertensive Myocardium: From Microscopic Lesions to Clinical Complications
      and Outcomes.
AB  - The chronic hemodynamic load imposed by hypertension on the left ventricle leads
      to lesions in the myocardium that result in structural remodeling, which provides
      support for alterations in cardiac function, perfusion, and electrical activity
      that adversely influence the clinical evolution of hypertensive heart disease.
      Management must include detecting, reducing, and reversing left ventricular
      hypertrophy, as well as the detection and repair of microscopic lesions
      responsible for myocardial remodeling. Reducing the burden associated with
      hypertensive heart disease can be targeted using personalized treatment. The
      noninvasive, biomarker-mediated identification of subsets of patients with
      hypertensive heart disease is essential to provide personalized treatment.

PMID- 27884235
TI  - Hypertension in Patients with Cardiac Transplantation.
AB  - Hypertension is a common complication among post cardiac transplant recipients
      affecting more than 95% of patients. Increased blood pressure poses a significant
      cardiovascular morbidity and mortality in these patients; it should be identified
      quickly and needs to be managed appropriately. Understanding the pathophysiology
      and contributing factors to this disease in these complex and unique patients is
      the key to appropriate treatment selection.

PMID- 27884232
TI  - Adherence to Antihypertensive Therapy.
AB  - Adherence to antihypertensive medication remains a key modifiable factor in the
      management of hypertension. The multidimensional nature of adherence and blood
      pressure (BP) control call for multicomponent, patient-centered interventions to
      improve adherence. Promising strategies to improve antihypertensive medication
      adherence and BP control include regimen simplification, reduction of out-of
      pocket costs, use of allied health professionals for intervention delivery, and
      self-monitoring of BP. Research to understand the effects of technology-mediated
      interventions, mechanisms underlying adherence behavior, and sex-race differences
      in determinants of low adherence and intervention effectiveness may enhance
      patient-specific approaches to improve adherence and disease control.

PMID- 27884237
TI  - Diastolic Dysfunction and Hypertension.
AB  - Left ventricular (LV) diastolic dysfunction (LVDD) is characterized by
      alterations in LV diastolic filling, and is a strong predictor of cardiovascular
      events and heart failure. Hypertension is the most important risk factor for LVDD
      in the community and promotes LVDD through several mechanisms, including
      hemodynamic overload and myocardial ischemia. Associated factors such as age,
      ethnicity, dietary sodium, obesity, diabetes mellitus, and chronic kidney disease
      also contribute to LVDD in hypertensive individuals. Blood pressure lowering
      using antihypertensive medications can improve LVDD; however, it remains unclear
      whether this improvement in LV diastolic function can improve cardiovascular
      outcomes.

PMID- 27884236
TI  - Renal Arterial Disease and Hypertension.
AB  - Renal artery disease produces a spectrum of progressive clinical manifestations
      ranging from minor degrees of hypertension to circulatory congestion and kidney
      failure. Moderate reductions in renal blood flow do not induce tissue hypoxia or
      damage, making medical therapy for renovascular hypertension feasible. Several
      prospective trials indicate that optimized medical therapy using agents that
      block the renin-angiotensin system should be the initial management. Evidence of
      progressive disease and/or treatment failure should allow recognition of high
      risk subsets that benefit from renal revascularization. Severe reductions in
      kidney blood flow ultimately activate inflammatory pathways that do not reverse
      with restoring blood flow alone.

PMID- 27884239
TI  - Continuing Challenges and Unresolved Problems in Hypertensive Diseases.

PMID- 27884240
TI  - The Sounds of Progress.

PMID- 27884238
TI  - The Pressure of Aging.
AB  - Significant hemodynamic changes ensue with aging, leading to an ever-growing
      epidemic of hypertension. Alterations in central arterial properties play a major
      role in these hemodynamic changes. These alterations are characterized by an
      initial decline in aortic distensibility and an increase of diastolic blood
      pressure, followed by a sharp increase in pulse wave velocity (PWV), and an
      increase in pulse pressure (PP) beyond the sixth decade. However, the
      trajectories of PWV and PP diverge with advancing age. There is an increased
      prevalence of salt-sensitive hypertension with advancing age that is, in part,
      mediated by marinobufagenin, an endogenous sodium pump ligand.

PMID- 27884241
TI  - A Prospective Natural History Study of Coronary Atherosclerosis Using Fractional
      Flow Reserve.
AB  - BACKGROUND: In patients with coronary artery disease, clinical outcome depends on
      the extent of reversible myocardial ischemia. Whether the outcome also depends on
      the severity of the stenosis as determined by fractional flow reserve (FFR)
      remains unknown. OBJECTIVES: This study sought to investigate the relationship
      between FFR values and vessel-related clinical outcome. METHODS: We prospectively
      studied major adverse cardiovascular events (MACE) at 2 years in 607 patients in
      whom all stenoses were assessed by FFR and who were treated with medical therapy
      alone. The relationship between FFR and 2-year MACE was assessed as a continuous
      function. Logistic and Cox proportional hazards regression models were used to
      calculate the average decrease in the risk of MACE per 0.05-U increase in FFR.
      RESULTS: MACE occurred in 272 (26.5%) of 1,029 lesions. Target lesions with
      diameter stenosis >=70% were more often present in the MACE group (p < 0.01).
      Median FFR was significantly lower in the MACE group versus the non-MACE group
      (0.68 [interquartile range: 0.54 to 0.77] vs. 0.80 [interquartile range: 0.70 to
      0.88]; p < 0.01). The cumulative incidence of MACE significantly increased with
      increasing FFR quartiles. An average decrease in MACE per 0.05-unit increase in
      FFR was statistically significant even after adjustment for all clinical and
      angiographic features (odds ratio: 0.81; 95% confidence interval: 0.76 to 0.86]).
      The strongest increase in MACE occurred for FFR values between 0.80 and 0.60. In
      multivariable Cox regression analysis, FFR was significantly associated with MACE
      up to 2 years (hazard ratio: 0.87; 95% confidence interval: 0.83 to 0.91]).
      CONCLUSIONS: In patients with stable coronary disease, stenosis severity as
      assessed by FFR is a major and independent predictor of lesion-related outcome.
      (FAME II - Fractional Flow Reserve [FFR] Guided Percutaneous Coronary
      Intervention [PCI] Plus Optimal Medical Treatment [OMT] Verses OMT; NCT01132495).

PMID- 27884242
TI  - Does the Natural History of Atherosclerosis Follow an Ischemic Dose-Response
      Curve?

PMID- 27884244
TI  - Should We Measure Biomarkers for Myonecrosis Before and After PCI?

PMID- 27884243
TI  - High-Sensitivity Troponin T and Mortality After Elective Percutaneous Coronary
      Intervention.
AB  - BACKGROUND: The prognostic value of high-sensitivity troponin T (hs-TnT)
      elevation after elective percutaneous coronary intervention (PCI) in patients
      with or without raised baseline hs-TnT levels is unclear. OBJECTIVES: The goal of
      this study was to assess whether the prognostic value of post-procedural hs-TnT
      level after elective PCI depends on the baseline hs-TnT level. METHODS: This
      study included 5,626 patients undergoing elective PCI who had baseline and peak
      post-procedural hs-TnT measurements available. The primary outcome was 3-year
      mortality (with risk estimates calculated per SD increase of the log hs-TnT
      scale). RESULTS: Patients were divided into 4 groups: nonelevated baseline and
      post-procedural hs-TnT levels (hs-TnT <=0.014 MUg/l; n = 742); nonelevated
      baseline but elevated post-procedural hs-TnT levels (peak post-procedural hs-TnT
      >0.014 MUg/l; n = 2,721); elevated baseline hs-TnT levels (hs-TnT >0.014 MUg/l)
      with no further rise post-procedure (n = 516); and elevated baseline hs-TnT
      levels with a further rise post-procedure (n = 1,647). A total of 265 deaths
      occurred: 6 (1.6%) in patients with nonelevated baseline and post-procedural hs
      TnT levels; 54 (3.8%) in patients with nonelevated baseline but elevated post
      procedural hs-TnT levels; 50 (16.0%) in patients with elevated baseline hs-TnT
      levels with no further rise post-procedure; and 155 (18.2%) in patients with
      elevated baseline hs-TnT levels with a further rise post-procedure (p < 0.001).
      After adjustment, baseline hs-TnT levels (hazard ratio [HR]: 1.22; 95% confidence
      interval [CI]: 1.09 to 1.38; p < 0.001) but not peak post-procedural hs-TnT
      levels (HR: 1.04; 95% CI: 0.85 to 1.28; p = 0.679) were associated with an
      increased risk of mortality. Peak post-procedural hs-TnT findings were not
      associated with mortality in patients with nonelevated (HR: 0.93; 95% CI: 0.69 to
      1.25; p = 0.653) or elevated (HR: 1.24; 95% CI: 0.91 to 1.69; p = 0.165) baseline
      hs-TnT levels. CONCLUSIONS: In patients with coronary artery disease undergoing
      elective PCI, an increase in post-procedural hs-TnT level did not offer
      prognostic information beyond that provided by the baseline level of the
      biomarker.

PMID- 27884246
TI  - Anticoagulant-Related Nephropathy: Is an AKI Elephant Hiding in Plain View?

PMID- 27884245
TI  - Acute Kidney Injury in Asians With Atrial Fibrillation Treated With Dabigatran or
      Warfarin.
AB  - BACKGROUND: Whether dabigatran is associated with a lower risk of acute kidney
      injury (AKI) in patients with nonvalvular atrial fibrillation (NVAF) remains
      unknown. OBJECTIVES: The authors compared the risk of AKI in Asians with NVAF who
      were prescribed dabigatran versus warfarin. METHODS: The authors analyzed
      patients enrolled in the Taiwan nationwide retrospective cohort study from June
      1, 2012, to December 31, 2013. Dabigatran and warfarin were taken by 7,702 and
      7,885 NVAF patients without a history of chronic kidney disease (CKD) and 2,256
      and 2,089 NVAF patients with a history of CKD, respectively. A propensity-score
      weighted method was used to balance covariates across study groups. RESULTS: A
      total of 6,762 (88%) and 940 (12%) CKD-free patients and 2,025 (90%) and 231
      (10%) CKD patients took dabigatran 110 mg and 150 mg twice daily, respectively.
      Dabigatran was associated with a lower risk of AKI than warfarin for either the
      CKD-free (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.49 to 0.77; p
      < 0.001) or CKD (HR: 0.56; 95% CI: 0.46 to 0.69; p < 0.001) cohort. As the
      increment in CHA2DS2-VASc score (a risk score based on congestive heart failure,
      hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient
      ischemic attack, vascular disease, aged 65 to 74 years, and female sex) increased
      from 0/1 to 6+ points, the incidence of AKI for the dabigatran group was
      relatively stable (1.87% to 2.91% per year for the CKD-free cohort; 7.31% to
      13.15% per year for the CKD cohort) but increased obviously for patients taking
      warfarin for either CKD-free (2.00% to 6.16% per year) or CKD cohorts (6.82 to
      26.03% per year). The warfarin group had a significantly higher annual risk of
      AKI than the dabigatran group for those with a high CHA2DS2-VASc score (>=4 for
      the CKD-free cohort and >=3 for the CKD cohort). Subgroup analysis revealed that
      among dabigatran users, those taking either low-dose or standard-dose dabigatran,
      those with a warfarin-naive or warfarin-experienced history, those with or
      without diabetes, and those with CHA2DS2-VASc >=4 or HAS-BLED >=3 (risk score
      based on hypertension, abnormal renal and liver function, stroke, prior major
      bleeding, labile international normalized ratios, age 65 years or older, drugs or
      alcohol usage history) all had a lower risk of AKI than those taking warfarin.
      CONCLUSIONS: Among Asians with NVAF, dabigatran is associated with a lower risk
      of AKI than warfarin.

PMID- 27884247
TI  - Machine-Learning Algorithms to Automate Morphological and Functional Assessments
      in 2D Echocardiography.
AB  - BACKGROUND: Machine-learning models may aid cardiac phenotypic recognition by
      using features of cardiac tissue deformation. OBJECTIVES: This study investigated
      the diagnostic value of a machine-learning framework that incorporates speckle
      tracking echocardiographic data for automated discrimination of hypertrophic
      cardiomyopathy (HCM) from physiological hypertrophy seen in athletes (ATH).
      METHODS: Expert-annotated speckle-tracking echocardiographic datasets obtained
      from 77 ATH and 62 HCM patients were used for developing an automated system. An
      ensemble machine-learning model with 3 different machine-learning algorithms
      (support vector machines, random forests, and artificial neural networks) was
      developed and a majority voting method was used for conclusive predictions with
      further K-fold cross-validation. RESULTS: Feature selection using an information
      gain (IG) algorithm revealed that volume was the best predictor for
      differentiating between HCM ands. ATH (IG = 0.24) followed by mid-left
      ventricular segmental (IG = 0.134) and average longitudinal strain (IG = 0.131).
      The ensemble machine-learning model showed increased sensitivity and specificity
      compared with early-to-late diastolic transmitral velocity ratio (p < 0.01),
      average early diastolic tissue velocity (e') (p < 0.01), and strain (p = 0.04).
      Because ATH were younger, adjusted analysis was undertaken in younger HCM
      patients and compared with ATH with left ventricular wall thickness >13 mm. In
      this subgroup analysis, the automated model continued to show equal sensitivity,
      but increased specificity relative to early-to-late diastolic transmitral
      velocity ratio, e', and strain. CONCLUSIONS: Our results suggested that machine
      learning algorithms can assist in the discrimination of physiological versus
      pathological patterns of hypertrophic remodeling. This effort represents a step
      toward the development of a real-time, machine-learning-based system for
      automated interpretation of echocardiographic images, which may help novice
      readers with limited experience.

PMID- 27884248
TI  - Machine Learning for Echocardiographic Imaging: Embarking on Another Incredible
      Journey.

PMID- 27884250
TI  - The Significant Arrhythmia and Cardiomyopathy Burden of Lamin A/C Mutations.

PMID- 27884251
TI  - Complicated Pericarditis: Understanding Risk Factors and Pathophysiology to
      Inform Imaging and Treatment.
AB  - Most patients with acute pericarditis have a benign course and a good prognosis.
      However, a minority of patients develop complicated pericarditis, and the care of
      these patients is the focus of this review. Specifically, we address risk
      factors, multimodality imaging, pathophysiology, and novel treatments. The
      authors conclude that: 1) early high-dose corticosteroids, a lack of colchicine,
      and an elevated high-sensitivity C-reactive protein are associated with the
      development of complicated pericarditis; 2) in select cases, cardiovascular
      magnetic resonance imaging may aid in the assessment of pericardial inflammation
      and constriction; 3) given phenotypic similarities between recurrent idiopathic
      pericarditis and periodic fever syndromes, disorders of the inflammasome may
      contribute to relapsing attacks; and 4) therapies that target the inflammasome
      may lead to more durable remission and resolution. Finally, regarding future
      investigations, the authors discuss the potential of cardiovascular magnetic
      resonance to inform treatment duration and the need to compare steroid-sparing
      treatments to pericardiectomy.

PMID- 27884249
TI  - Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers.
AB  - BACKGROUND: Mutations in LMNA are variably expressed and may cause
      cardiomyopathy, atrioventricular block (AVB), or atrial arrhythmias (AAs) and
      ventricular arrhythmias (VA). Detailed natural history studies of LMNA-associated
      arrhythmic and nonarrhythmic outcomes are limited, and the prognostic
      significance of the index cardiac phenotype remains uncertain. OBJECTIVES: This
      study sought to describe the arrhythmic and nonarrhythmic outcomes of LMNA
      mutation carriers and to assess the prognostic significance of the index cardiac
      phenotype. METHODS: The incidence of AVB, AA, sustained VA, left ventricular
      systolic dysfunction (LVD) (= left ventricular ejection fraction <=50%), and end
      stage heart failure (HF) was retrospectively determined in 122 consecutive LMNA
      mutation carriers followed at 5 referral centers for a median of 7 years from
      first clinical contact. Predictors of VA and end-stage HF or death were
      determined. RESULTS: The prevalence of clinical manifestations increased broadly
      from index evaluation to median follow-up: AVB, 46% to 57%; AA, 39% to 63%; VA,
      16% to 34%; and LVD, 44% to 57%. Implantable cardioverter-defibrillators were
      placed in 59% of patients for new LVD or AVB. End-stage HF developed in 19% of
      patients, and 13% died. In patients without LVD at presentation, 24% developed
      new LVD, and 7% developed end-stage HF. Male sex (p = 0.01), nonmissense
      mutations (p = 0.03), and LVD at index evaluation (p = 0.004) were associated
      with development of VA, whereas LVD was associated with end-stage HF or death (p
      < 0.001). Mode of presentation (with isolated or combination of clinical
      features) did not predict sustained VA or end-stage HF or death. CONCLUSIONS:
      LMNA-related heart disease was associated with a high incidence of phenotypic
      progression and adverse arrhythmic and nonarrhythmic events over long-term follow
      up. The index cardiac phenotype did not predict adverse events. Genetic diagnosis
      and subsequent follow-up, including anticipatory planning for therapies to
      prevent sudden death and manage HF, is warranted.

PMID- 27884252
TI  - Differentiation of Constriction and Restriction: Complex Cardiovascular
      Hemodynamics.
AB  - Differentiation of constrictive pericarditis (CP) from restrictive cardiomyopathy
      (RCM) is a complex and often challenging process. Because CP is a potentially
      curable cause of heart failure and therapeutic options for RCM are limited,
      distinction of these 2 conditions is critical. Although different in regard to
      etiology, prognosis, and treatment, CP and RCM share a common clinical
      presentation of predominantly right-sided heart failure, in the absence of
      significant left ventricular systolic dysfunction or valve disease, due to
      impaired ventricular diastolic filling. Fundamental to the diagnosis of either
      condition is a clear understanding of the underlying hemodynamic principles and
      pathophysiology. We present a contemporary review of the pathophysiology,
      hemodynamics, diagnostic assessment, and therapeutic approach to patients
      presenting with CP and RCM.

PMID- 27884253
TI  - The Quest for New Approaches in Myocarditis and Inflammatory Cardiomyopathy.
AB  - Myocarditis is a diverse group of heart-specific immune processes classified by
      clinical and histopathological manifestations. Up to 40% of dilated
      cardiomyopathy is associated with inflammation or viral infection. Recent
      experimental studies revealed complex regulatory roles for several
      microribonucleic acids and T-cell and macrophage subtypes. Although the
      prevalence of myocarditis remained stable between 1990 and 2013 at about 22 per
      100,000 people, overall mortality from cardiomyopathy and myocarditis has
      decreased since 2005. The diagnostic and prognostic value of cardiac magnetic
      resonance has increased with new, higher-sensitivity sequences. Positron emission
      tomography has emerged as a useful tool for diagnosis of cardiac sarcoidosis. The
      sensitivity of endomyocardial biopsy may be increased, especially in suspected
      sarcoidosis, by the use of electrogram guidance to target regions of abnormal
      signal. Investigational treatments on the basis of mechanistic advances are
      entering clinical trials. Revised management recommendations regarding athletic
      participation after acute myocarditis have heightened the importance of early
      diagnosis.

PMID- 27884254
TI  - Troponin Testing for Clinicians.
AB  - The analytical performance of troponin assays has improved markedly in the last 2
      decades. The variety of assays, their evolution over time, and their critical
      importance in influencing care, mandates the need for skills in their use. There
      are 3 critical elements necessary for optimal use of troponin testing in clinical
      care, as follows: 1) the analytical performance of the assay; 2) the clinical
      sensitivity and specificity of the test result; and 3) the clinical reasoning for
      ordering and the proper clinical context for interpreting the test result. This
      paper provides further explanation that will assist clinicians in their clinical
      decision making and interpretation of troponin test results. Schematic visual
      explanations are provided to help clinicians develop a more intuitive
      understanding of troponin testing.

PMID- 27884255
TI  - Fellowship Training in Cardiology: Finding Synergies Between Academic Program
      Clinical Competencies and ACC-Developed Nonclinical Competencies.

PMID- 27884256
TI  - The Quest to Become a Master Teacher: One Cardiologist's Story and
      Recommendations for Others.

PMID- 27884257
TI  - Reported Versus "Real" Incidence of New Pacemaker Implantation Post-Transcatheter
      Aortic Valve Replacement.

PMID- 27884258
TI  - Cardiac Phenotype and Long-Term Follow-Up of Patients With Mutations in NKX2-5
      Gene.

PMID- 27884259
TI  - Why to Replace an ACE or ARB With an ARB/Neprilysin Inhibitor?

PMID- 27884260
TI  - Reply: Why to Replace an ACE or ARB With an ARB/Neprilysin Inhibitor?

PMID- 27884261
TI  - Risk Scores From PARIS Registry: Are They Useful in a Contemporary Cohort of ACS
      Patients?

PMID- 27884262
TI  - Reply: Risk Scores From PARIS Registry: Are They Useful in a Contemporary Cohort
      of ACS Patients?

PMID- 27884264
TI  - Yet another good reason to decrease elective early-term births.

PMID- 27884263
TI  - Non-Weight-Bearing and Weight-Bearing Ultrasonography of Select Foot Muscles in
      Young, Asymptomatic Participants: A Descriptive and Reliability Study.
AB  - OBJECTIVE: The primary aim of this study was to determine the reliability of
      diagnostic ultrasound imaging for select intrinsic foot muscles using both non
      weight-bearing and weight-bearing postures. Our secondary aim was to describe the
      change in muscle cross-sectional area (CSA) and dorsoplantar thickness when
      bearing weight. METHODS: An ultrasound examination was performed with a linear
      ultrasound transducer operating between 9 and 12 MHz. Long-axis and short-axis
      ultrasound images of the abductor hallucis, flexor digitorum brevis, and
      quadratus plantae were obtained in both the non-weight-bearing and weight-bearing
      postures. Two examiners independently collected ultrasound images to allow for
      interexaminer and intraexaminer reliability calculation. The change in muscle CSA
      and dorsoplantar thickness when bearing weight was also studied. RESULTS: There
      were 26 participants (17 female) with a mean age of 25.5 +/- 3.8 years and a mean
      body mass index of 28.0 +/- 7.8 kg/m2. Inter-examiner reliability was excellent
      when measuring the muscles in short axis (intraclass correlation coefficient
      >0.75) and fair to good in long axis (intraclass correlation coefficient >0.4).
      Intraexaminer reliability was excellent for the abductor hallucis and flexor
      digitorum brevis and ranged from fair to good to excellent for the quadratus
      plantae. Bearing weight did not reduce interexaminer or intraexaminer
      reliability. All muscles exhibited a significant increase in CSA when bearing
      weight. CONCLUSIONS: This is the first report to describe weight-bearing
      diagnostic ultrasound of the intrinsic foot muscles. Ultrasound imaging is
      reliable when imaging these muscles bearing weight. Furthermore, muscle CSA
      increases in the weight-bearing posture.

PMID- 27884266
TI  - Just say no to opioids!

PMID- 27884265
TI  - Preventive care for children receiving steroids.

PMID- 27884268
TI  - Tonsillectomy for incomplete PFAPA?

PMID- 27884269
TI  - Precision medicine?

PMID- 27884267
TI  - 50 Years Ago in The Journal of Pediatrics: Hemodynamic Findings in Acute
      Glomerulonephritis.

PMID- 27884270
TI  - Reconciling competing interests in the treatment of respiratory syndrome.

PMID- 27884271
TI  - Newborns and red reflexes.

PMID- 27884272
TI  - 50 Years Ago in TheJournal ofPediatrics: Antinuclear Factors in Childhood
      Rheumatic Diseases.

PMID- 27884273
TI  - 50 Years Ago in The Journal of Pediatrics: The Irritable Colon of Childhood
      (Chronic Nonspecific Diarrhea Syndrome).

PMID- 27884274
TI  - 50 Years Ago in The Journal of Pediatrics: Dysmorphology (Teratology).

PMID- 27884275
TI  - 50 Years Ago in The Journal of Pediatrics: Familial Metabolic Disorder with Fatty
      Metamorphosis of the Viscera.

PMID- 27884276
TI  - Ten Years Atop the Masthead.

PMID- 27884277
TI  - DASH and Mediterranean Diets as Nutritional Interventions for CKD Patients.

PMID- 27884278
TI  - Lifetime Probabilities of ESRD: A Decade of Disparity.

PMID- 27884279
TI  - Patient-Oriented Research: Clinical Innovation Based on CKD Patients' Priorities
      for Care.

PMID- 27884280
TI  - Autosomal Dominant Polycystic Kidney Disease and Ventricular Noncompaction:
      Unanswered Questions.

PMID- 27884281
TI  - In Reply to 'Autosomal Dominant Polycystic Kidney Disease and Ventricular
      Noncompaction: Unanswered Questions'.

PMID- 27884282
TI  - Quiz Page December 2016: Anuria on the Second Day Following Kidney
      Transplantation.

PMID- 27884283
TI  - AJKD Atlas of Renal Pathology: Thrombotic Microangiopathy.

PMID- 27884284
TI  - AJKD Atlas of Renal Pathology: Cytomegalovirus Infection.

PMID- 27884285
TI  - AJKD Atlas of Renal Pathology: Polyomavirus Nephropathy.

PMID- 27884286
TI  - NIH's Essential 21st-Century Research Challenge: Enhancing Scientific Workforce
      Diversity.

PMID- 27884287
TI  - The Role of Entrepreneurial Leadership and Innovation in the Future of
      Therapeutic Dermatology.

PMID- 27884288
TI  - TREX through Cutaneous Health and Disease.
AB  - TREX1 and 2 are exonucleases that repair and degrade DNA. Degradation of DNA is
      involved in maintaining the integrity of the epidermis. The importance of these
      enzymes to cutaneous integrity is observed when TREX1 and TREX2 pathways become
      aberrant, and autoimmune or cancerous diseases ensue. Manils et al. have now
      shown that overexpression of TREX2 may play a role in potentiating psoriasis.
      Thus, these pathways are likely targets for novel therapeutics.

PMID- 27884289
TI  - Psoriasis Therapy: Breakthroughs in Pharmacogenomics or in Pharmacology?
AB  - As the cost of psoriasis therapies skyrockets, it becomes increasingly important
      to find biomarkers that predict which patients will respond to expensive
      medications. The ability to predict response to a specific therapy is
      particularly important for medications that are effective in only a small portion
      of the population. As we develop medications that clear most patients, the need
      for a predictive biomarker diminishes. Nevertheless, the importance of
      pharmacogenomics is likely to increase as the cost of drugs continues to rise.

PMID- 27884290
TI  - Atopic Dermatitis According to GARP: New Mechanistic Insights in Disease
      Pathogenesis.
AB  - In complex disease such as atopic dermatitis, the journey from identification of
      strong risk loci to profound functional and mechanistic insights can take several
      years. Here, Manz et al. have elegantly deciphered the mechanistic pathways in
      the well-established 11q13.5 atopic dermatitis risk locus. Their genetic and
      functional insights emphasize a role for T regulatory cells in atopic dermatitis
      pathogenesis.

PMID- 27884291
TI  - Bioinformatic Analysis of Gene Expression for Melanoma Treatment.
AB  - Bioinformatic analysis of genome-wide gene expression allows us to characterize
      cells, including melanomas. Gene expression profiles have been generated in
      various stages of melanomas and analyzed by researchers in unique ways. Lauss et
      al. compared their melanoma subtypes with those of The Cancer Genome Atlas
      Network and found consistency between the two studies.

PMID- 27884292
TI  - Mission Accomplished?

PMID- 27884293
TI  - Bridging the Gap between Clinical Medicine and its Underlying Science.

PMID- 27884294
TI  - A Serendipitous Retreat into Research Techniques Made Simple.

PMID- 27884295
TI  - Research Techniques Made Simple: Workflow for Searching Databases to Reduce
      Evidence Selection Bias in Systematic Reviews.
AB  - Clinical trials and basic science studies without statistically significant
      results are less likely to be published than studies with statistically
      significant results. Systematic reviews and meta-analyses that omit unpublished
      data are at high risk of distorted conclusions. Here, we describe methods to
      search beyond bibliographical databases to reduce evidence selection bias in
      systematic reviews. Unpublished studies may be identified by searching conference
      proceedings. Moreover, clinical trial registries-databases of planned and ongoing
      trials-and regulatory agency websites such as the European Medicine Agency (EMA)
      and the United States Food and Drug Administration (FDA) may provide summaries of
      efficacy and safety data. Primary and secondary outcomes are prespecified in
      trial registries, thus allowing the assessment of outcome reporting bias by
      comparison with the trial report. The sources of trial data and documents are
      still evolving, with ongoing initiatives promoting broader access to clinical
      study reports and individual patient data. There is currently no established
      methodology to ensure that the multiple sources of information are incorporated.
      Nonetheless, systematic reviews must adapt to these improvements and cover the
      new sources in their search strategies.

PMID- 27884298
TI  - MHY1485 activates mTOR and protects osteoblasts from dexamethasone.
AB  - Dexamethasone (Dex) exerts cytotoxic effects to cultured osteoblasts. The
      potential effect of MHY1485, a small-molecular mammalian target of rapamycin
      (mTOR) activator, against the process was studied here. In both osteoblastic
      MC3T3-E1 cells and primary murine osteoblasts, treatment with MHY1485
      significantly ameliorated Dex-induced cell death and apoptosis. mTOR inhibition,
      through mTOR kinase inhibitor OSI-027 or mTOR shRNAs, abolished MHY1485-mediated
      osteoblast cytoprotection against Dex. Intriguingly, activation of mTOR complex
      (mTORC1), but not mTORC2, is required for MHY1485's anti-Dex activity. mTORC1
      inhibitors (rapamycin and RAD001) or Raptor knockdown almost reversed MHY1485
      induced osteoblast cytoprotection. mTORC2 inhibition, via shRNA knockdown of
      Rictor, failed to affect MHY1485's activity in MC3T3-E1 cells. Further studies
      showed that MHY1485 treatment in MC3T3-E1 cells and primary murine osteoblasts
      significantly inhibited Dex-induced mitochondrial death pathway activation, the
      latter was tested by mitochondrial depolarization, cyclophilin D-ANT-1
      association and cytochrome C cytosol release. Together, these results suggest
      that MHY1485 activates mTORC1 signaling to protect osteoblasts from Dex.

PMID- 27884299
TI  - Understanding the Impact That Marketing, Advertising, and Promotion Have on
      Adolescent E-cigarette Behavior.

PMID- 27884302
TI  - Folic acid supplementation and chronic kidney disease progression.
AB  - In contrast to prior studies demonstrating no benefit or even increased harm from
      B vitamin supplementation in patients with chronic kidney disease, a large
      randomized trial from China recently demonstrated small but statistically
      significant reductions in the risk of first stroke and chronic kidney disease
      progression with the addition of folic acid to enalapril in adults with
      hypertension. Differences in the study population and study intervention may
      explain these discordant results.

PMID- 27884300
TI  - Teen Preferences for Clinic-Based Behavior Screens: Who, Where, When, and How?
AB  - PURPOSE: Previous research examining computer-based adolescent risk behavior
      screening was done before widespread adoption of smartphones and merits updating.
      METHODS: This is a cross-sectional survey among 115 adolescents seeking primary
      care age 12-18 years. It is a diverse sample with 59% female, 51% white, 18%
      African-American, and 27% Latino. Respondents were asked level of comfort and
      honesty (1 = strongly disagree, 5 = strongly agree) when answering health
      behavior questions by paper, interview, or electronic device. Differences in the
      level of agreement were tested using a Wilcoxon signed rank test. RESULTS:
      Adolescents reported a higher level of comfort and honesty for screening
      conducted via electronic device versus paper (90% vs. 57%, p < .001; 89% vs. 61%,
      p < .001). Sixty-two percent adolescents prefer waiting room electronic screening
      versus at home (4.7%) or by provider in the examination room (11.2%).
      CONCLUSIONS: Electronic same-day risk behavior screening is the preferred method
      for adolescents and should be incorporated into preventive services.

PMID- 27884303
TI  - Aberrant mTORC1 activation kills tubular cells by inactivating miR148b-3p.
AB  - A new study by Kuwagata et al. now shows that aberrant activation of the
      mechanistic target of rapamycin complex 1 in renal tubular cells causes their
      injury and cell death by enhancing endoplasmic reticulum stress and cell death
      pathway under diabetic conditions. The study has revealed a novel molecular
      mechanism in which mechanistic target of rapamycin complex 1 stimulates the tumor
      necrosis factor signaling by attenuating miR-148b-3p, thereby deteriorating renal
      tubular cell dysfunction under diabetic conditions.

PMID- 27884304
TI  - A remedy for kidney disease successfully alters the cold shock protein response
      during inflammation.
AB  - Kidneys undergoing acute inflammatory responses are characterized by cell
      infiltration and a cytokinergic milieu. The hazard resides in the perpetuation of
      inflammation and ensuing fibrosis. In this issue of Kidney International, Wang et
      al.4 identify the cold shock Y-box binding protein-1 as the key orchestrator of
      cell infiltration in experimental tubulointerstitial nephritis following ureteral
      obstruction. Intriguingly, a small molecule previously designed to interfere with
      Y-box binding protein-1 interactions mediates an anti-inflammatory response and
      halts fibrogenesis.

PMID- 27884305
TI  - MicroRNAs in extracellular vesicles protect kidney from ischemic injury: from
      endothelial to tubular epithelial.
AB  - Extracellular vesicles from stem cells or progenitor cells are novel therapeutic
      systems for acute kidney injury. With exosomes (the smallest class of
      extracellular vesicles), Vinas et al. successfully rescued ischemic injured
      kidney. MicroRNA-486-5p, the crucial factor specifically delivered by exosomes to
      kidney, ameliorates the injury by targeting phosphatase and tensin homolog and
      inhibiting endothelial cell apoptosis. In this commentary, we discuss the
      potential underlying mechanism and the pivotal impact of their study on
      extracellular vesicle therapy.

PMID- 27884306
TI  - Commentary for "human kidney pericytes produce renin".
AB  - Renin-secreting cells of the kidney display several particularities, including
      their intrarenal localization in the fetal and in the adult kidney, their
      ultrastructure, and the mode by which they secrete renin into circulation to
      trigger the activity of the renin-angiotensin-aldosterone system. The cell type
      from which renin cells differentiate has long been subject to speculation. The
      paper by Stefanska et al. now strongly suggests that renin cells are or derive
      from pericytes.

PMID- 27884307
TI  - Extended hours hemodialysis and survival: extended hours, extended evidence?
AB  - Extended-hours hemodialysis presents another approach to the intensification of
      therapy for maintenance hemodialysis recipients. Smaller studies have
      demonstrated several potential benefits with this modality, but the impact on
      patient-centered outcomes has been unclear. We review the largest published study
      to compare survival among patients who received extended-hours hemodialysis with
      those who received conventional hemodialysis.

PMID- 27884308
TI  - Talking back: the podocytes and endothelial cells duke it out.
AB  - Thrombotic microangiopathy has numerous causes and may result in chronic kidney
      disease with secondary glomerulosclerosis. Detailed analyses of this interplay of
      lesions have been lacking. Buob et al. report on their adult, mostly Caucasian
      patients, showing frequent sclerosis, most often of collapsing type, with worse
      prognosis than in those without segmental scars. The complex interplay of
      glomerular cells and possible ways in which the endothelial cells may talk back
      to the podocytes, and vice versa, are discussed.

PMID- 27884309
TI  - Would prescribing target Kt dose adjusted for body surface area improve
      hemodialysis outcomes?
AB  - The use of Kt/V to prescribe and monitor hemodialysis adequacy remains the
      current standard, although it is increasingly questioned. Alternative proposals
      for dose prescription and monitoring have been advocated. In a noninterventional,
      prospective study reported in this issue, Maduell et al., utilizing online ionic
      dialysance, explore the association between outcome measures (mortality and
      hospitalization rates) and the extent to which delivered Kt dose achieved minimal
      target Kt doses calculated from individual estimates of body surface area.

PMID- 27884310
TI  - Normalizing the peritoneal dialysis dose-have we got it right?
AB  - How the dialysis dose is normalized is just one of several assumptions that
      clinicians need to take into account when prescribing peritoneal dialysis. El
      Kateb et al. confirm that estimating the volume of urea distribution is
      associated with significant error and show that energy expenditure is not
      linearly related to volume, such that there is a potential need for a higher
      dialysis prescription in smaller, more active individuals.

PMID- 27884312
TI  - Management of patients with diabetes and CKD: conclusions from a "Kidney Disease:
      Improving Global Outcomes" (KDIGO) Controversies Conference.
AB  - The prevalence of diabetes around the world has reached epidemic proportions and
      is projected to increase to 642 million people by 2040. Diabetes is already the
      leading cause of end-stage kidney disease (ESKD) in most developed countries, and
      the growth in the number of people with ESKD around the world parallels the
      increase in diabetes. The presence of kidney disease is associated with a
      markedly elevated risk of cardiovascular disease and death in people with
      diabetes. Several new therapies and novel investigational agents targeting
      chronic kidney disease patients with diabetes are now under development. This
      conference was convened to assess our current state of knowledge regarding
      optimal glycemic control, current antidiabetic agents and their safety, and new
      therapies being developed to improve kidney function and cardiovascular outcomes
      for this vulnerable population.

PMID- 27884314
TI  - Chronic massive pneumoperitoneum.

PMID- 27884311
TI  - Understanding kidney care needs and implementation strategies in low- and middle
      income countries: conclusions from a "Kidney Disease: Improving Global Outcomes"
      (KDIGO) Controversies Conference.
AB  - Evidence-based cinical practice guidelines improve delivery of uniform care to
      patients with and at risk of developing kidney disease, thereby reducing disease
      burden and improving outcomes. These guidelines are not well-integrated into care
      delivery systems in most low- and middle-income countries (LMICs). The KDIGO
      Controversies Conference on Implementation Strategies in LMIC reviewed the
      current state of knowledge in order to define a road map to improve the
      implementation of guideline-based kidney care in LMICs. An international group of
      multidisciplinary experts in nephrology, epidemiology, health economics,
      implementation science, health systems, policy, and research identified key
      issues related to guideline implementation. The issues examined included the
      current kidney disease burden in the context of health systems in LMIC, arguments
      for developing policies to implement guideline-based care, innovations to improve
      kidney care, and the process of guideline adaptation to suit local needs. This
      executive summary serves as a resource to guide future work, including a pathway
      for adapting existing guidelines in different geographical regions.

PMID- 27884313
TI  - Normal body mass index with central obesity has increased risk of coronary artery
      calcification in Korean patients with chronic kidney disease.
AB  - In chronic kidney disease (CKD), overweight and mild obesity have shown the
      lowest cardiovascular (CV) risk. However, central obesity has been directly
      associated with CV risk in these patients. This bidirectional relationship of
      body mass index (BMI) and central obesity prompted us to evaluate CV risk based
      on a combination of BMI and waist-to-hip ratio (WHR) in nondialysis CKD patients.
      We included 1078 patients with CKD stage 2 through 5 (nondialysis) enrolled in a
      nationwide prospective cohort of Korea. Patients were divided into 3 groups by
      BMI (normal BMI, 18.5-22.9; overweight, 23.0-27.4; and obese, 27.5 and over
      kg/m2) and were dichotomized by a sex-specific median WHR (0.92 in males and 0.88
      in females). Coronary artery calcification (CAC) was determined by multislice
      computed tomography. CAC (score above 10 Agatston units) was found in 477
      patients. Multivariate logistic regression analysis indicated that BMI was not
      independently associated with CAC. However, WHR showed an independent linear and
      significant association with CAC (odds ratio, 1.036; 95% confidence interval,
      1.007-1.065 per 0.01 increase). Furthermore, when patients were categorized into
      6 groups according to a combination of BMI and WHR, normal BMI but higher WHR had
      the highest risk of CAC compared with the normal BMI with lower WHR group (2.104;
      1.074-4.121). Thus, a normal BMI with central obesity was associated with the
      highest risk of CAC, suggesting that considering BMI and WHR, 2 surrogates of
      obesity, can help to discriminate CV risk in Korean nondialysis CKD patients.

PMID- 27884315
TI  - Melanonychia following cyclophosphamide therapy.

PMID- 27884316
TI  - The Case | Seizure, ophthalmoplegia, and amnesia in a peritoneal dialysis
      patient.

PMID- 27884317
TI  - The Case | Unexplained fever and acute kidney injury in a kidney transplant
      patient.

PMID- 27884318
TI  - N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia
      reperfusion.
AB  - BACKGROUND: N-acetylcysteine (NAC) is an antioxidant with direct and indirect
      antioxidant actions used in the clinical setting. Oxidative stress is known to
      play a pivotal role in the intestinal ischemia reperfusion (IIR). Therefore, we
      studied the effect of different pretreatment regimens with NAC on the IIR injury
      in rats. MATERIALS AND METHODS: Thirty-five male Wistar rats were randomly
      assigned to five groups. In group sham, only laparotomy was performed. Group
      control underwent IIR without NAC. In the other groups, NAC was administered
      intraperitoneally with different regimens: 150 mg/kg before ischemia (NAC 150),
      300 mg/kg before ischemia (NAC 300), and 150 mg/kg before ischemia plus 150 mg/kg
      5 min before reperfusion (NAC 150 + 150). Measurements in tissues and blood were
      conducted at 4 h of reperfusion following exsanguination. RESULTS: Histological
      score of the liver was significantly improved in NAC 300 compared with control
      (1.7 +/- 0.5 versus 2.9 +/- 1.1, respectively, P = 0.05). In addition, NAC
      treatment significantly reduced liver transaminases in all groups of treatment,
      mostly in group NAC 300. Plasma malondialdehyde levels were lower with NAC
      treatment, although not statistically significant. Lung glutathione peroxidase
      was significantly increased in group NAC 300 (P = 0.04), while the other
      oxidation biomarkers showed no significant differences. CONCLUSIONS: NAC exerts a
      significant protective role in liver injury following IIR, which seems to be
      independent of an intestinal protective effect. Additional administration of NAC
      before reperfusion was of no further benefit. The most effective regimen among
      the compared regimens was that of 300 mg/kg before ischemia.

PMID- 27884319
TI  - Student views on the role of self-regulated learning in a surgery clerkship.
AB  - BACKGROUND: Self-regulated learning, including student-generated learning goals
      and flexibility in the learning structure are increasingly being used to enhance
      medical education. The role of these practices in surgical education of medical
      students has not been studied. MATERIALS AND METHODS: We administered an 18
      question electronic survey to all third-year medical students at Washington
      University in St. Louis School of Medicine. Of the 126 students invited, 64
      responded and 56 were included in the analysis. RESULTS: We found that third-year
      medical students develop learning goals at the beginning of the surgery
      clerkship. Although these learning goals theoretically can be a mechanism for
      enhanced student-faculty engagement, students are not aware of formal mechanisms
      for sharing these goals with faculty members. Furthermore, students report a lack
      of flexibility within the surgery clerkship and discomfort with requesting
      specific learning opportunities. Finally, students report that they believe
      increased flexibility could improve student engagement, learning, and the overall
      clerkship experience. CONCLUSIONS: We therefore propose that a mechanism for
      students to share their learning goals with faculty and an infrastructure in
      which student learning experiences can be tailored to fit with these
      individualized goals would enhance student surgical learning.

PMID- 27884320
TI  - Prediction of procalcitonin for postoperative intraabdominal infections after
      definitive operation of intestinal fistulae.
AB  - BACKGROUND: Inflammatory biomarkers usually start to rise earlier before the
      infection becomes clinically evident. This study was designed to evaluate the
      predictive performance of procalcitonin (PCT), C-reactive protein (CRP), and
      white blood cell (WBC) counts in postoperative intraabdominal infections (IAIs)
      after definitive operation of intestinal fistulae. MATERIAL AND METHODS: We
      prospectively enrolled a total of 356 consecutive patients who underwent elective
      digestive tract reconstruction for gastrointestinal fistulae without existing
      clinical infection. Plasma PCT levels, serum CRP concentration, and WBC counts
      were assessed preoperatively and on postoperative days (PODs) 1, 3, 5, and 7. The
      predictive value of each laboratory marker for IAIs was calculated. RESULTS: The
      occurrence rate of IAIs after elective digestive tract reconstruction for
      gastrointestinal fistulae in our study was 7.3%. Both PCT levels and WBC counts
      were significantly higher in patients with IAIs than those in patients without
      IAIs on POD 1, POD 3, and POD 5, whereas CRP levels differed significantly on POD
      3 and POD 5. Receiver-operating characteristics demonstrated that PCT on POD 3
      had the highest diagnostic accuracy for IAIs, and the area under the curve
      reached 0.86, with a sensitivity of 92.0% and specificity of 74.0%. CONCLUSIONS:
      The value of PCT above 0.98 ng/L on POD 3 and 0.83 ng/L on POD 5 could predict
      the occurrence of IAIs after definitive operations for intestinal fistulae.

PMID- 27884321
TI  - The role of computed tomography after emergent trauma operation.
AB  - BACKGROUND: Although computed tomography (CT) has become the preferred diagnostic
      modality, immediate surgical intervention is often required for severely injured
      patients with minimum preoperative radiographic evaluation. The utility of
      postoperative CT (postop-CT) for the identification of undiagnosed injuries and
      its impact on patient management remain unclear. The purpose of this study was to
      evaluate the utility of postop-CT for the identification of clinically
      significant injuries in patients who underwent an emergent life-saving procedure.
      METHODS: A 5-y retrospective study from 2009 to 2013 was conducted at a high
      volume level I trauma center. We included blunt and penetrating trauma patients
      who underwent an emergent operation (neck exploration, thoracotomy, and
      laparotomy) without preoperative CT. Postop-CT was obtained within 48 h after the
      initial operation at the discretion of the attending trauma surgeon.
      Characteristics of newly diagnosed injuries on postop-CT were analyzed. These
      injuries were considered clinically significant when the patient required (1)
      immediate intervention; (2) new consultation from a specialty service; or (3) a
      higher level of care. RESULTS: A total of 89 patients met our inclusion criteria
      (five neck explorations, 16 thoracotomies, and 74 laparotomies) with the
      following characteristics: median age of 30 y, 87.6% male, 47.2% penetrating
      injury, and median injury severity score of 24. New injuries were identified on
      postop-CT in 59 cases (66%), and clinical management was changed in 51 cases
      (57%). Patients with an admission Glasgow Coma Scale <15 and solid organ injury
      identified during the index operation were more likely to have new injuries on
      postop-CT. CONCLUSIONS: In patients undergoing an emergent operation before
      having their full diagnostic workup completed, postop-CT often demonstrates
      clinically significant injuries. Further prospective study to identify the
      patients who will benefit from postop-CT is warranted.

PMID- 27884322
TI  - VAC-instillation therapy in abdominal mesh exposure: a novel indication.
AB  - BACKGROUND: Defects of the abdominal wall pose a problem for general surgeons
      that negatively affects patient prognosis. In cases of abdominal wall wound
      dehiscence and exposed abdominal mesh, conservative treatment has not been proven
      effective to date. We aimed to study patient outcomes in cases of abdominal wall
      wound dehiscence with mesh exposure treated with vacuum-assisted closure system
      with intermittent instillation (VAC-instillation) as a temporary cover to achieve
      wound closure. METHODS: A retrospective cohort study was performed to evaluate
      and compare the outcomes of 45 patients with postoperative abdominal wall wound
      dehiscence and exposed mesh: 34 were treated with conventional dressings and 11
      with the VAC-instillation device. Clinical records were reviewed, and patient
      demographics, indication for abdominal surgery, and existing risk factors were
      noted. Patient outcome was evaluated in terms of number of reoperations, length
      of hospital stay, and total time of treatment. RESULTS: Demographic features did
      not differ significantly between the two groups. Patients treated with
      conventional dressings required a significantly higher number of surgeries to
      achieve wound closure. We did not find statistical differences between the two
      groups regarding length of hospital stay, but the VAC-instillation group showed a
      significantly shorter total time of treatment. The incidence of complications was
      lower in the VAC-instillation group, though hernia recurrence rate was slightly
      higher in these patients. CONCLUSIONS: VAC-instillation is a valid option for the
      conservative treatment of critical patients with abdominal wall wound dehiscence
      and exposed infected mesh that allows recovery with fewer surgeries and
      complications and avoids the need of mesh removal.

PMID- 27884323
TI  - The toll-like receptor 4 antagonist transforming growth factor-beta-activated
      kinase(TAK)-242 attenuates taurocholate-induced oxidative stress through
      regulating mitochondrial function in mice pancreatic acinar cells.
AB  - BACKGROUND: Acute pancreatitis (AP) is a commonly occurring and potentially life
      threatening disease. Recently, toll-like receptor 4 (TLR4) has been considered as
      a new clue for studying the pathogenesis of AP due to its important role in
      inflammatory response cascade. MATERIALS AND METHODS: The aim of this study was
      to investigate the potential protective effect of transforming growth factor-beta
      activated kinase (TAK)-242, a novel TLR4 antagonist, in taurocholate-treated mice
      pancreatic acinar cells. The protective effects were measured by cell viability,
      lactate dehydrogenase release and apoptosis, and oxidative stress was assayed by
      lipid peroxidation and oxidative enzyme activities. To determine the potential
      underlying mechanisms, mitochondrial cytochrome c release, swelling, and calcium
      buffering capacity were measured in isolated mitochondria, and mitochondrial
      biogenesis and expression of mitochondrial dynamic proteins were detected by
      reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.
      RESULTS: Treatment with 6-mM taurocholate significantly increased the expression
      of TLR4 at both mRNA and protein levels. TAK-242 markedly increased cell
      viability, decreased lactate dehydrogenase release, and inhibited apoptotic cell
      death as measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin
      nick end labeling (TUNEL) staining in pancreatic acinar cells. These protective
      effects were accompanied by the suppressed lipid peroxidation and enhanced
      endogenous antioxidative enzyme activity. Using isolated and purified
      mitochondria from pancreatic acinar cells, we found that TAK-242 treatment also
      inhibited cytochrome c release into the cytoplasm, mitochondrial swelling, and
      decrease in mitochondrial Ca2+ buffering capacity after taurocholate exposure. In
      addition, TAK-242 significantly promoted mitochondrial biogenesis, as evidenced
      by increased mtDNA and upregulated mitochondrial transcription factors. The
      results of Western blot analysis showed that TAK-242 also differently regulated
      the expression of mitochondrial fusion and fission proteins. CONCLUSIONS: All
      these data strongly indicated that blocking TLR4 activity via TAK-242 exerts
      protective effects in an in vitro AP model, and it could be a possible strategy
      to improve clinical outcome in AP patients.

PMID- 27884324
TI  - Postconditioning with sevoflurane ameliorates spatial learning and memory deficit
      after hemorrhage shock and resuscitation in rats.
AB  - BACKGROUND: Severe hemorrhage shock and resuscitation are a systemic ischemia
      reperfusion phenomenon which can induce learning and memory deficit in human and
      rats. Sevoflurane postconditioning has been proved to offer neuroprotection under
      different setting of cerebral ischemia-reperfusion in rats. The aim of this study
      was to investigate whether sevoflurane postconditioning could improve spatial
      learning and memory ability after hemorrhage shock and resuscitation in rats.
      METHODS: Thirty-five male rats were randomized into five groups: sham group,
      shock group, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%),
      and high concentration (sevo3, 3.6%) of sevoflurane postconditioning groups. The
      spatial learning and memory ability of rats were measured by Morris water maze 3
      d after the operation. The expression of choline acetyltransferase (CHAT) and
      acetylcholinesterase (ACHE) in the hippocampus CA1 region was observed by
      immunohistochemistry method after the Morris water maze test. RESULTS: The
      ability of spatial learning and memory of rats and the expression of CHAT was
      significantly declined, while the expression of ACHE increased in the shock group
      compared with the sham group (P < 0.05). Sevoflurane postconditioning with the
      concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning
      and memory ability and increased the expression of CHAT and decreased the
      expression of ACHE in hippocampal CA1 region when compared with shock group (P <
      0.05). CONCLUSIONS: Postconditioning with sevoflurane at the concentrations of
      2.4% and 3.6% which improved the ability of spatial learning and memory after
      hemorrhage shock and resuscitation in rats may involve the protection of the
      cholinergic neurons in hippocampal CA1 region.

PMID- 27884326
TI  - Appropriate timing of blood sampling for blood gas analysis in the ventilated
      rabbit.
AB  - BACKGROUND: Arterial and venous blood gas analyses (BGAs) are essential to
      evaluate devices that measure biological oxygenation. The appropriate timing of
      blood sampling for BGA after respiratory rate (RR) change in animal experiments
      has not been reported. This study investigated the appropriate timing of blood
      sampling for BGA in ventilated rabbits and whether venous samples are an
      alternative to arterial samples. MATERIALS AND METHODS: Under general anesthesia,
      14 rabbits (body weight, 3.02 +/- 0.09 kg) were ventilated and their RR was
      changed (40/min, 30/min, and 20/min). Blood was sampled through cervical arterial
      and venous catheters. Experiment 1: in seven rabbits, arterial BGA was measured
      at 0, 0.5, 1, 2, 3, 5, 10, 15, and 20 min after the RR change. Experiment 2: in
      seven different rabbits, simultaneous arterial and venous BGA were measured at 0,
      2, 5, 10, 15, and 20 min after the RR change. RESULTS: Oxygen partial pressure
      (PO2) and saturation (SO2) of the arterial blood stabilized 0.5 min after the RR
      changed. In venous BGA, no index stabilized during observation. The arterial and
      venous values of the carbon dioxide partial pressure (PCO2) and pH had
      significant correlations (arterial PCO2 = 0.9316 * venous PCO2-4.4425 [r =
      0.9178]; arterial pH = 1.0835 * venous pH-0.5795 [r = 0.9453]). CONCLUSIONS: In
      ventilated rabbits, arterial PO2 and SO2 stabilized in 0.5 min. No venous value
      stabilized after the RR change. Only the PCO2 and pH of venous samples may be an
      alternative to arterial samples under the defined formula.

PMID- 27884325
TI  - Violet 405-nm light: a novel therapeutic agent against common pathogenic
      bacteria.
AB  - BACKGROUND: The increasing incidence of healthcare-associated infections (HAIs)
      and multidrug-resistant organisms demonstrate the need for innovative
      technological solutions. Staphylococcus aureus, Streptococcus pneumonia,
      Escherichia coli, and Pseudomonas aeruginosa in particular are common pathogens
      responsible for a large percentage of indwelling medical device-associated
      clinical infections. The bactericidal effects of visible light sterilization
      (VLS) using 405-nm is one potential therapeutic under investigation. MATERIALS
      AND METHODS: Light-emitting diodes of 405-nm were used to treat varying
      concentrations of S aureus, S pneumonia, E coli, and P aeruginosa. Irradiance
      levels between 2.71 +/- 0.20 to 9.27 +/- 0.36 mW/cm2 and radiant exposure levels
      up to 132.98 +/- 6.68 J/cm2 were assessed. RESULTS: Dose-dependent effects were
      observed in all species. Statistically significant reductions were seen in both
      Gram-positive and Gram-negative bacteria. At the highest radiant exposure levels,
      bacterial log10 reductions were E coli-6.27 +/- 0.54, S aureus-6.10 +/- 0.60, P
      aeruginosa-5.20 +/- 0.84, and S pneumoniae-6.01 +/- 0.59. Statistically
      significant results (<0.001*) were found at each time point. CONCLUSIONS: We have
      successfully demonstrated high-efficacy bacterial reduction using 405-nm light
      sterilization. The VLS showed statistical significance against both Gram-positive
      and Gram-negative species with the given treatment times. The beta-lactam
      antibiotic-resistant E coli was the most sensitive to VLS, suggesting light
      therapy could a suitable option for sterilization in drug-resistant bacterial
      species. This research illustrates the potential of using VLS in treating
      clinically relevant bacterial infections.

PMID- 27884327
TI  - Inhibition of c-Jun N-terminal kinase signaling suppresses skin flap apoptosis in
      a rat ischemia and/or reperfusion model.
AB  - BACKGROUND: The goals of this study were to validate the role of c-Jun N-terminal
      kinase (JNK) activation in skin flap apoptosis in a rat model of abdomen skin
      ischemia and/or reperfusion (IR) and to compare the protective effect of SP600125
      and hydrogen-rich saline in skin IR injury. METHODS: Male Sprague-Dawley rats
      were divided into five groups: one sham surgery group and four surgery groups.
      Before undergoing 3 h of IR management, the surgery groups were treated with
      normal saline (IR), dimethyl sulfoxide, SP600125 (SP), and hydrogen-rich saline
      (H). On the third postoperative day, blood perfusion of the flap was measured
      using Laser Doppler flowmeters. Hematoxylin and eosin staining was used to
      observe morphologic changes. Early apoptosis was observed using TdT-mediated dUTP
      X nick end-labeling staining. pASK-1, pJNK, Bcl-2, and Bax were examined by
      immunodetection. Caspase-3 activity was also measured 24 h after reperfusion.
      RESULTS: Compared to the IR group and the dimethyl sulfoxide group, the SP group
      and the H group had larger skin flap survival area, more blood perfusion and
      lower levels of caspase-3 activity. The SP and the H groups had high expression
      levels of Bcl-2 and low expression levels of pASK-1 and pJNK. Bax was
      significantly decreased in the SP group. In addition, cell apoptosis was
      decreased in both the sham surgery and the H groups. CONCLUSIONS: IR-induced JNK
      phosphorylation was reduced by SP600125, indicating that JNK mediates the
      apoptosis pathways in rat skin. In the SP and the H groups, the apoptotic factors
      measured showed similar expression levels, indicating that JNK inhibition during
      IR may be associated with H-mediated protection against skin IR apoptosis.

PMID- 27884328
TI  - Effects of diagnosis-related group payment system on appendectomy outcomes.
AB  - BACKGROUND: The voluntary diagnosis-related group (DRG) payment system was
      introduced in 2002. Since July 2013, the Korean government has mandated DRG
      participation for all hospitals. The main purpose of this study was to examine
      the effects of mandatory DRG participation on various outcome metrics for
      appendectomy patients. MATERIALS AND METHODS: We collected inpatient DRG data for
      280,062 appendectomy patients between 2007 and 2014 using the Health Insurance
      Review and Assessment database. We examined patient outcome metrics such as
      length of stay (LOS), total medical cost, spillover, and readmission rate,
      according to hospital size. RESULTS: As a result of DRG participation, the
      average LOS for patients decreased (adjusted ratio: 0.83 [large hospitals], 0.83
      [small hospitals]; 95% confidence interval [CI]: 0.82-0.84, 0.82-0.84), the total
      medical costs of patients increased (adjusted ratio: 1.23 [large hospitals], 1.35
      [small hospitals]; 95% CI: 1.22-1.24, 1.34-1.36), the spillover of patients
      increased (adjusted ratio: 2.10 [large hospitals], 2.30 [small hospitals]; 95%
      CI: 2.03-2.18, 2.16-2.45), and the readmission rates of appendectomy patients
      decreased (adjusted ratio: 0.85 [large hospitals], 0.49 [small hospitals]; 95%
      CI: 0.77-0.94, 0.42-0.57). CONCLUSIONS: The mandatory implementation of the DRG
      payment system in South Korea has led to significant reductions in LOS and
      readmission rates for appendectomy patients. However, any resulting expansion of
      outpatient services may result in unnecessary resource usage rather than
      improving medical quality. Policy makers should consider the various implications
      reflected by these results when considering DRGs for other diseases.

PMID- 27884329
TI  - Saphenous artery-based flap models in rats: new flap designs for experimental
      studies.
AB  - BACKGROUND: Experimental research using laboratory animals provides substantial
      data about reconstructive surgery. However, the literature does not include any
      experimental studies that have used flap models on the hind limbs of rats. To
      gain an understanding of the physiology of lower-extremity flaps and of flap
      failures, this study assessed the cutaneous perforators of the saphenous artery,
      and new flap models were designed for the hind limbs of rats. MATERIALS AND
      METHODS: The experiment was designed to include three stages and used 35 rats.
      The first stage involved mapping the perforators of the saphenous artery. In the
      second stage, the contents and structures of McFarlane, epigastric, and anterior
      hind limb flap tissues were compared histologically. The third stage of the study
      involved designing and comparing different flaps for the hind limbs of the rats
      and included random flaps, perforator-based peninsular flaps, perforator-based
      island flaps, and perforator-based flaps with rotated pedicles. Postoperative
      necrosis ratios were evaluated using computer-based software. RESULTS: Mapping of
      the saphenous artery perforators revealed an average of 2.2 septocutaneous
      arteries in each hind limb. Histologic studies showed thick dermis and panniculus
      carnosus in the McFarlane flaps, thick dermis, and thin panniculus carnosus
      layers in the epigastric flaps, and thin subcutaneous tissue with no panniculus
      carnosus tissue in the skin of the hind limbs. The results of the flap studies
      that used random flaps showed a 52.4% necrosis, while there was no necrosis when
      perforator-based peninsular flaps, island flaps, and flaps with rotated pedicles
      were used. CONCLUSIONS: New flap models used on the saphenous artery perforators
      of the hind limbs of rats can provide valuable information about the physiology
      of lower-extremity flaps. New studies can also be designed based on these flap
      models to acquire more knowledge about pathologic conditions such as ischemia and
      venous insufficiency.

PMID- 27884330
TI  - Factors associated with adverse events after emergency laparotomy in Cape Town,
      South Africa: identifying opportunities for quality improvement.
AB  - BACKGROUND: Surgical outcomes research is limited in areas of the world with the
      greatest unmet surgical need and likely greatest variation in outcomes.
      Measurement alone may improve outcomes-the so-called Hawthorne effect. The
      purpose of this multicenter cohort study was to identify factors that are both
      feasible to collect and are associated with a major adverse event following a
      targeted procedure in Cape Town, South Africa. METHODS: A collaborative of four
      acute care surgical units was formed to develop a data set with minimal data
      burden describing outcomes after an emergency exploratory laparotomy during a 3
      mo period (February-April 2015). Controlling for patient, problem, provider,
      procedure and process predictors, multivariate models were built to identify risk
      factors for a major adverse event and higher resource use after surgery in our
      collaborative. RESULTS: The outcomes of 450 exploratory laparotomies from the
      four participating hospitals were audited, 319 (70.9%) were for non-trauma and
      131 (29.1%) were for trauma. The major adverse event rate was 15.7% (95% CI 12.6
      19.4). In the multivariate analysis, factors associated with the primary outcome
      included age, American Society of Anesthesia score of greater than 2, bowel
      resection, preoperative CT scan, and a nontherapeutic laparotomy. A major adverse
      event was associated with all three outcomes assessing increased resource
      utilization. CONCLUSIONS: This study supports the comparative outcome assessment
      of a high-volume or high-risk procedure as a proxy for measuring the quality of
      care provided in a surgical collaborative. Such an exercise can identify
      opportunities for quality improvement.

PMID- 27884331
TI  - Inhibition of acquired-resistance hepatocellular carcinoma cell growth by
      combining sorafenib with phosphoinositide 3-kinase and rat sarcoma inhibitor.
AB  - BACKGROUND: To provide support for combined usage of phosphoinositide 3-kinase
      (PI3K) inhibitors or mitogen-activated protein kinase pathway inhibitors together
      with sorafenib in treatment of sorafenib-resistant hepatocellular carcinoma.
      MATERIALS AND METHODS: The sorafenib-resistant cell lines were established to
      evaluate the effects of MK-2206 2HCL, a dual PI3K/mammalian target of rapamycin
      (mTOR) inhibitor, and PD0325901, an rat sarcoma (RAS) and/or extracellular signal
      regulated kinase (ERK) inhibitor, on cell proliferation and apoptosis, as both
      single and combined treatments with sorafenib. In addition, multidrug resistance
      1 gene expression, mutation status of key members in PI3K/mTOR, and RAS/ERK
      pathways and pathway activation were analyzed to identify predictors of drug
      response. RESULTS: Molecular studies reveal that combining MK-2206 2HCL or
      PD0325901 with sorafenib not only has a synergistic effect, in suppressing
      PI3K/protein kinase B/mTOR and RAS/MEK/ERK signaling more effectively than either
      treatment alone, but also prevents the cross activation of the other pathway that
      occurs with single treatments in both sorafenib sensitive and resistant lines.
      PD0325901 exhibited a stronger synergic effect with sorafenib than MK-2206 2HCL.
      Sorafenib-resistant cell lines were characterized by activation of both of the
      two pathways, as indicated by multidrug resistance 1 gene expression profiles and
      pathway activity analysis. CONCLUSIONS: Our studies have showed that both
      inhibitors of PI3K/mTOR and RAS/ERK signaling are potentially effective
      antihepatocellular carcinoma drugs especially in treating sorafenib-resistant
      hepatocellular carcinoma.

PMID- 27884332
TI  - Thoracostomy tube function not trajectory dictates reintervention.
AB  - BACKGROUND: Hemothorax and/or pneumothorax can be managed successfully managed
      with tube thoracostomy (TT) in the majority of cases. Improperly placed tubes are
      common with rates near 30%. This study aimed to determine whether TT trajectory
      affects the rate of secondary intervention. METHODS: A retrospective review of
      all adult trauma patients undergoing TT placement over a 4-y period was
      performed. TT trajectory was classified as ideal, nonideal, or kinked-based on
      anterior-posterior chest x-ray. TTs with sentinel port outside the thoracic
      cavity were excluded. The primary outcome was any secondary intervention.
      RESULTS: Four-hundred eighty-six patients and a total of 547 hemithoraces
      underwent placement and met inclusion criteria. The majority of patients were
      male (76%), with a median age of 41 y, and majority suffered blunt trauma ideal
      trajectory was identified in 429 (78.4%). Kinked TTs were noted in 33 (6%)
      hemothoraces with a 45.5% replacement rate. Review with staff demonstrates
      inherent bias to replace kinked TTs. The overall secondary intervention rate was
      27.8%. Kinked TTs were removed from final analysis due to treatment bias.
      Subsequent analysis demonstrated no significant difference between ideal and
      nonideal trajectories (25.1% versus 34.1%, P = 0.09). CONCLUSIONS: Intrathoracic
      trajectory of nonkinked TTs with the sentinel port within the thoracic cavity
      does not affect secondary intervention rates, including the rate of surgical
      intervention.

PMID- 27884333
TI  - C-spine injury and mandibular fractures: lifesaver broken in two spots.
AB  - BACKGROUND: Trauma is a leading cause of injury and mortality and may involve
      mandibular fractures and cervical spine injuries. Manipulation of the spine
      during trauma protocols and operative treatment has the potential to cause
      serious spinal cord injuries. The purpose of this study was to identify risk
      factors associated with cervical spine injury (CSI) in patients with mandibular
      fractures. METHODS: The National Trauma Databank (2007-2010) was used to identify
      patients with mandibular fractures. RESULTS: A total of 59,028 patients were
      identified and separated into adult and pediatric cohorts. There were 50,711
      adults (86%) and 8317 children (14%). There were statistically significant lower
      rates of associated CSI in pediatric patients than adults (3.5% versus 7.3%, P <
      0.01). Predictors of associated CSI in mandible fractures for both adults and
      children were older age, lower Glasgow Coma Scale, thoracic injuries, firearm or
      motor vehicle accident mechanisms, and symphyseal fractures. In the pediatric
      cohort, body, ramus, and subcondylar fractures were significantly associated with
      CSI. In adults, female gender, and upper extremity, abdominopelvic, and head
      injuries were also significantly associated with CSI. CONCLUSIONS: Multiple
      mandibular fractures were inversely correlated with CSI. One possibility is that
      energy dissipation in the mandible with multiple fractures is protective of the C
      spine leading to fewer fractures. Children and adults had different associations
      in the pattern of mandible fractures concomitant with CSI. This has implications
      in management, imaging, and workup of trauma patients.

PMID- 27884334
TI  - Assessment of the incidence of chronic pain and discomfort after primary inguinal
      hernia repair.
AB  - BACKGROUND: Chronic pain and discomfort is a notable complication after inguinal
      hernia repair. This study assesses the incidence and degree of chronic pain and
      discomfort after primary inguinal hernia repair performed in our hospital and
      aims to clarify its relationship to the type of mesh placement. MATERIALS AND
      METHODS: A retrospective analysis was conducted of 334 patients (378 lesions) who
      underwent primary inguinal hernia using the Lichtenstein (onlay mesh), Ultrapro
      Plug (UPP; onlay plus plug mesh), modified Kugel Patch (onlay and underlay mesh),
      or laparoscopic transabdominal preperitoneal (TAPP; underlay mesh) procedure.
      Postoperative pain was assessed using a numerical rating scale at postoperative 2
      3 wk, 3 mo, and 6 mo. Postoperative discomfort was assessed 6 mo afterward.
      RESULTS: Questionnaire responses were received for 378 lesions (100%) after 2-3
      wk, 229 (60.6%) after 3 mo, and 249 (65.9%) after 6 mo. The majority of chronic
      pain experienced was mild, and no patient suffered from severe pain. The level of
      pain tended to be less for the TAPP procedure than for other methods. Discomfort
      at rest was significantly less for TAPP versus Ultrapro Plug (P < 0.01), and
      discomfort with movement was significantly less for TAPP versus modified Kugel (P
      < 0.05). CONCLUSIONS: Onlay mesh appears to be a risk factor in chronic pain and
      discomfort. The lower level of chronic pain and discomfort with underlay mesh
      placement is considered to result from the reduced risk of nerve damage in this
      procedure than in the onlay mesh placement procedure.

PMID- 27884335
TI  - Pneumonia prevention in intubated patients given sucralfate versus proton-pump
      inhibitors and/or histamine II receptor blockers.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is a common cause of infectious
      morbidity and mortality in the intensive care unit (ICU). The type of stress
      ulcer prophylaxis (SUP) given to ventilated patients may, in part, be
      responsible. We observed an increase in VAP as ventilator bundle compliance
      increased and a decrease in VAP when bundle compliance decreased. We reasoned
      that SUP which raises gastric pH such as proton-pump inhibitors (PPIs) and
      histamine II (H2) receptor antagonists as opposed to SUP which does not raise pH
      such as sucralfate (S) may be responsible and also may alter the causative
      bacteria. MATERIALS AND METHODS: This is a single-center retrospective cohort
      analysis of all intubated, adult surgical patients admitted to the surgical ICU
      between January and June during the 3-y period 2012-2014. Demographics, APACHE
      II, Injury Severity Score, VAP occurrence, culprit bacteria, ventilator days, and
      ICU days were recorded based on the type of SUP given. RESULTS: There were 45
      instances of VAP in the 504 study patients, 33 in the PPI/H2 group, and 12 in the
      S group (P < 0.01). VAP per 1000 ventilator days were 10.2 for PPI/H2 and 3.7 for
      S (P < 0.01). Culprit bacteria were mostly Pseudomonas, gram-negative bacilli,
      and methicillin-resistant Staphylococcus aureus in PPI/H2 patients (n = 29)
      compared with oropharyngeal flora in S patients (n = 6; P < 0.001). CONCLUSIONS:
      There was a substantial difference in VAP occurrence and in the culprit bacteria
      between S and PPI/H2 treated patients due perhaps to gastric alkalization.

PMID- 27884336
TI  - Predictive value of clinical scoring and simplified gait analysis for acetabulum
      fractures.
AB  - BACKGROUND: Fractures of the acetabulum show a high, long-term complication rate.
      The aim of the present study was to determine the predictive value of clinical
      scoring and standardized, simplified gait analysis on the outcome after these
      fractures. METHODS: Forty-one patients with acetabular fractures treated between
      2008 and 2013 and available, standardized video recorded aftercare were
      identified from a prospective database. A visual gait score was used to determine
      the patients walking abilities 6-m postoperatively. Clinical (Merle d'Aubigne and
      Postel score, visual analogue scale pain, EQ5d) and radiological scoring
      (Kellgren-Lawrence score, postoperative computed tomography, and Matta
      classification) were used to perform correlation and multivariate regression
      analysis. RESULTS: The average patient age was 48 y (range, 15-82 y), six female
      patients were included in the study. Mean follow-up was 1.6 y (range, 1-2 y).
      Moderate correlation between the gait score and outcome (versus EQ5d: rs = 0.477;
      versus Merle d'Aubigne: rs = 0.444; versus Kellgren-Lawrence: rs = -0.533), as
      well as high correlation between the Merle d'Aubigne score and outcome were seen
      (versus EQ5d: rs = 0.575; versus Merle d'Aubigne: rs = 0.776; versus Kellgren
      Lawrence: rs = -0.419). Using a multivariate regression model, the 6 m gait score
      (B = -0.299; P < 0.05) and early osteoarthritis development (B = 1.026; P < 0.05)
      were determined as predictors of final osteoarthritis. A good fit of the
      regression model was seen (R2 = 904). CONCLUSIONS: Easy and available clinical
      scoring (gait score/Merle d'Aubigne) can predict short-term radiological and
      functional outcome after acetabular fractures with sufficient accuracy. Decisions
      on further treatment and interventions could be based on simplified gait
      analysis.

PMID- 27884338
TI  - The effect of local hyperglycemia on skin cells in vitro and on wound healing in
      euglycemic rats.
AB  - BACKGROUND: Multiple previous studies have established that high systemic blood
      glucose concentration impairs skin wound healing. However, the effects of local
      hyperglycemia on wound healing are not well defined. Comprehensive animal studies
      and in vitro studies using both fibroblasts and keratinocytes are lacking.
      MATERIALS AND METHODS: Primary keratinocytes and fibroblasts were isolated from
      discarded human tissue, cultured under different concentrations of glucose, and
      the effect on cell function was examined. In addition, a rat full-thickness wound
      model was used to topically treat the wounds with different glucose
      concentrations and the effect on wound closure and re-epithelialization was
      investigated over time. RESULTS: The cell viability experiments indicated that
      both keratinocytes and fibroblasts endure high glucose well and concentrations
      under 26 mM did not have a remarkable effect on their viability over time.
      Moderate addition of glucose (10 mM) boosted fibroblast proliferation (6-fold)
      but did not have an effect on keratinocyte proliferation. In both keratinocytes
      and fibroblasts, glucose inhibited their migration and already the addition of
      5.6-mM glucose had an inhibitory effect. In vivo experiments showed that full
      thickness wounds treated with topical glucose had impaired wound closure and
      lower re-epithelialization rate in comparison to nontreated control wounds. The
      results also showed that higher glucose concentrations inhibited wound healing
      more efficiently. CONCLUSIONS: In conclusion, our study indicates that high
      glucose inhibits both keratinocyte and fibroblast migration as well as wound
      healing in vivo in a concentration dependent manner.

PMID- 27884337
TI  - Using community outreach to explore health-related beliefs and improve surgeon
      patient engagement.
AB  - BACKGROUND: Fostering surgeon engagement in community outreach was recently
      identified as a major priority toward reducing health care disparities in
      surgery. We aimed to increase surgeon engagement in the local community,
      understand prevalent beliefs, and identify educational opportunities in the local
      community regarding cancer screening and treatment using community outreach.
      MATERIALS AND METHODS: In collaboration with the university's cancer center, the
      medical student surgical interest group, surgical faculty, and residents
      developed a community outreach program. The program consisted of networking time,
      a formal presentation, panel discussion, and question and answer time. A survey
      was distributed to all participants before the educational session, and a program
      assessment was distributed at the program's conclusion. RESULTS: A total of 256
      community members and 22 surgical volunteers attended at least one of the two
      events. Attendees were insured (175; 92.7%), female (151; 80%), and African
      American (176; 93.1%), with a mean age of 61 y (standard deviation 14.0). About
      56 participants (29.6%) were unwilling to undergo screening colonoscopy. Forty
      eight respondents (25.4%) endorsed mistrust in doctors and 25% believed surgery
      causes cancer to spread; a significantly higher proportion of them aged <60 y
      old. About 113 (59.8%) and 87 (46.1%) misunderstood the definitions of malignant
      and metastatic, respectively. Males were more unsure than females (61% versus
      55%, P = 0.5 and 70% versus 55%; P = 0.01). CONCLUSIONS: Risk perceptions related
      to fatalism, mistrust, or lack of knowledge were prevalent. The ability of
      surgeons to reach at-risk populations in the prehospital setting is an important
      opportunity waiting to be capitalized upon.

PMID- 27884339
TI  - Dose-dependent mortality and organ injury in a cecal slurry peritonitis model.
AB  - BACKGROUND: The cecal slurry model was introduced as an alternative method for
      creating an animal sepsis model. This study was performed to evaluate dose
      dependent mortality and organ injury in a sepsis model of cecal slurry
      peritonitis. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into
      5.0, 7.5, 10, or 15 mL/kg groups, according to the volume of cecal slurry
      administered into the peritoneal cavity. In the survival study, rats were
      observed for 14 d after sepsis induction. In the second experiment, blood and
      tissue were harvested to measure organ injury and the 2', 7'-dichlorofluorescein
      diacetate concentrations. RESULTS: All rats in the 5.0 mL/kg group survived for
      14 d, whereas all rats in the 15 mL/kg group died within 24 h. The survival rates
      in the 7.5 mL/kg and 10 mL/kg groups were 60% and 30%, respectively. In the
      arterial blood gas analysis, lactate concentrations increased and HCO3- decreased
      in a dose-dependent manner across the groups. Alanine aminotransferase and blood
      urea nitrogen concentrations increased as the dose of cecal slurry increased. 2',
      7'-Dichlorofluorescein diacetate concentrations also increased in a dose
      dependent manner. CONCLUSIONS: The cecal slurry model of sepsis evaluated in this
      study demonstrates dose-dependent mortality, metabolic acidosis, liver and kidney
      injuries, and reactive oxygen species production, and it could be used for
      subsequent sepsis experiments, considering the severity of sepsis induced.

PMID- 27884340
TI  - Use of an experimental model to evaluate infection resistance of meshes in
      abdominal wall surgery.
AB  - BACKGROUND: Staphylococcal species are the most common organisms causing
      prosthetic mesh infections, however, infections due to rapidly growing
      mycobacteria are increasing. This study evaluates the resistance of biomaterial
      for abdominal wall prostheses against the development of postoperative infection
      in a rat model. MATERIAL AND METHODS: In 75 rats, we intramuscularly implanted
      three different types of prostheses: (1) low-density polypropylene monofilament
      mesh (PMM), (2) high-density PMM, and (3) a composite prosthesis composed of low
      density PMM and a nonporous hydrophilic film. Meshes were inoculated with a
      suspension containing 108 colony-forming units of Staphylococcus aureus,
      Staphylococcus epidermidis, Mycobacterium fortuitum, or Mycobacterium abscessus
      before wound closure. Animals were sacrificed on the eighth day postoperatively
      for clinical evaluation, and the implants were removed for bacteriologic
      analyses. RESULTS: Prostheses infected with S aureus showed a higher bacterial
      viability, worse integration, and clinical outcome compared with infection by
      other bacteria. Composite prostheses showed a higher number of viable colonies of
      both M fortuitum and Staphylococcus spp., with poorer integration in host tissue.
      However, when the composite prosthesis was infected with M abscessus, a lower
      number of viable bacteria were isolated and a better integration was observed
      compared with infection by other bacteria. CONCLUSIONS: Considering M abscessus,
      a smaller collagen-free contact surface shows better resistance to infection,
      however, depending on the type of bacteria, prostheses with a large surface, and
      covered with collagen shows reduced resistance to infection, worse integration,
      and worse clinical outcome.

PMID- 27884341
TI  - Propofol inhibits T-helper cell type-2 differentiation by inducing apoptosis via
      activating gamma-aminobutyric acid receptor.
AB  - BACKGROUND: Propofol has been shown to attenuate airway hyperresponsiveness in
      asthma patients. Our previous study showed that it may alleviate lung
      inflammation in a mouse model of asthma. Given the critical role of T-helper cell
      type-2 (Th2) differentiation in asthma pathology and the immunomodulatory role of
      the gamma-aminobutyric acid type A (GABAA) receptor, we hypothesized that
      propofol could alleviate asthma inflammation by inhibiting Th2 cell
      differentiation via the GABA receptor. METHODS: For in vivo testing, chicken
      ovalbumin-sensitized and challenged asthmatic mice were used to determine the
      effect of propofol on Th2-type asthma inflammation. For in vitro testing, Th2
      type cytokines as well as the cell proliferation and apoptosis were measured to
      assess the effects of propofol on Th2 cell differentiation and determine the
      underlying mechanisms. RESULTS: We found that propofol significantly decreased
      inflammatory cell counts and interleukin-4 and inflammation score in vivo.
      Propofol, but not intralipid, significantly reduced the Th2-type cytokine
      interleukin-5 secretion and caused Th2 cell apoptosis without obvious inhibition
      of proliferation in vitro. A GABA receptor agonist simulated the effect of
      propofol, whereas pretreatment with an antagonist reversed this effect.
      CONCLUSIONS: This study demonstrates that the antiinflammatory effects of
      propofol on Th2-type asthma inflammation in mice are mediated by inducing
      apoptosis without compromising proliferation during Th2 cell differentiation via
      activation of the GABA receptor.

PMID- 27884342
TI  - Optimizing neurogenic potential of enteric neurospheres for treatment of
      neurointestinal diseases.
AB  - BACKGROUND: Enteric neurospheres derived from postnatal intestine represent a
      promising avenue for cell replacement therapy to treat Hirschsprung disease and
      other neurointestinal diseases. We describe a simple method to improve the
      neuronal yield of spontaneously formed gut-derived neurospheres. MATERIALS AND
      METHODS: Enteric neurospheres were formed from the small and large intestines of
      mouse and human subjects. Neurosphere size, neural crest cell content, cell
      migration, neuronal differentiation, and neuronal proliferation in culture were
      analyzed. The effect of supplemental neurotrophic factors, including glial cell
      line-derived neurotrophic factor (GDNF) and endothelin-3, was also assessed.
      RESULTS: Mouse small intestine-derived neurospheres contained significantly more
      P75-expressing neural crest-derived cells (49.9 +/- 15.3% versus 21.6 +/- 11.9%,
      P < 0.05) and gave rise to significantly more Tuj1-expressing neurons than colon
      derived neurospheres (69.9 +/- 8.6% versus 46.2 +/- 15.6%, P < 0.05). A similar
      pattern was seen in neurospheres isolated from human small and large intestine
      (32.6 +/- 17.5% versus 10.2 +/- 8.2% neural crest cells, P < 0.05; 29.7 +/- 16.4%
      versus 16.0 +/- 13.5% enteric neurons, P < 0.05). The addition of GDNF to the
      culture media further improved the neurogenic potential of small intestinal
      neurospheres (75.9 +/- 4.0% versus 67.8 +/- 5.8%, P < 0.05) whereas endothelin-3
      had no effect. CONCLUSIONS: Enteric neurospheres formed from small intestine and
      supplemented with GDNF yield an enriched population of neural crest-derived
      progenitor cells and give rise to a high density of enteric neurons.

PMID- 27884344
TI  - Do resident's leadership skills relate to ratings of technical skill?
AB  - BACKGROUND: This study sought to compare general surgery research residents'
      survey information regarding self-efficacy ratings to their observed performance
      during a simulated small bowel repair. Their observed performance ratings were
      based on their leadership skills in directing their assistant. METHODS:
      Participants were given 15 min to perform a bowel repair using bovine intestines
      with standardized injuries. Operative assistants were assigned to help assist
      with the repair. Before the procedure, participants were asked to rate their
      expected skills decay, task difficulty, and confidence in addressing the small
      bowel injury. Interactions were coded to identify the number of instructions
      given by the participants to the assistant during the repair. Statistical
      analyses assessed the relationship between the number of directional instructions
      and participants' perceptions self-efficacy measures. Directional instructions
      were defined as any dialog by the participant who guided the assistant to perform
      an action. RESULTS: Thirty-six residents (58.3% female) participated in the
      study. Participants who rated lower levels of decay in their intraoperative
      decision-making and small bowel repair skills were noted to use their assistant
      more by giving more instructions. Similarly, a higher number of instructions
      correlated with lower perceived difficulty in selecting the correct suture,
      suture pattern, and completing the entire surgical task. CONCLUSIONS: General
      surgery research residents' intraoperative leadership skills showed significant
      correlations to their perceptions of skill decay and task difficulty during a
      bowel repair. Evaluating resident's directional instructions may provide an
      additional individualized intraoperative assessment metric. Further evaluation
      relating to operative performance outcomes is warranted.

PMID- 27884343
TI  - Increased tolerance to stress in cardiac expressed gain-of-function of adenosine
      triphosphate-sensitive potassium channel subunit Kir6.1.
AB  - BACKGROUND: The adenosine triphosphate-sensitive potassium (KATP) channel opener
      diazoxide (DZX) prevents myocyte volume derangement and reduced contractility
      secondary to stress. KATP channels are composed of pore-forming (Kir6.1 or
      Kir6.2) and regulatory (sulfonylurea receptor, SUR1 or SUR2) subunits. Gain of
      function (GOF) of Kir6.1 subunits has been implicated in cardiac pathology in
      Cantu syndrome in humans (cardiomegaly, lymphedema, and pericardial effusions).
      We hypothesized that GOF of Kir6.1 subunits would result in altered myocyte
      response to stress. MATERIALS AND METHODS: Isolated cardiac myocytes from wild
      type (WT) and transgenic Kir6.1GOF mice were exposed to Tyrode's physiologic
      solution for 20 min, test solution (Tyrode's or stress [hyperkalemic cardioplegia
      {CPG, known myocyte stress}] +/- KATP channel opener DZX), followed by Tyrode's
      for 20 min. Myocyte volume and contractility were measured and compared. RESULTS:
      WT myocytes demonstrated significant swelling in response to stress, but
      significantly less swelling was seen in Kir6.1GOF myocytes. DZX prevented
      swelling secondary to CPG in WT but resulted in a nonsignificant reduction in
      swelling in Kir6.1GOF myocytes. Both WT and Kir6.1GOF myocytes demonstrated a
      reduction in contractility during stress, although this was only significant in
      Kir6.1GOF myocytes. DZX was not associated with an improvement in contractility
      in Kir6.1GOF myocytes following stress. CONCLUSIONS: Similar to previous results
      in Kir6.1(-/-) myocytes, Kir6.1GOF myocytes demonstrate resistance (less volume
      derangement) to stress of cardioplegia. Understanding the role of Kir6.1 in
      myocyte response to stress may aid in the treatment of patients with Cantu
      syndrome and warrants further investigation.

PMID- 27884345
TI  - Wound-edge protection devices in gastrointestinal surgery: a meta-analysis.
AB  - BACKGROUND: The role of wound-edge protection devices (WEPDs) in wound infection
      prevention is still controversial. The aim of this meta-analysis was to assess
      the protective efficiency of WEPDs in gastrointestinal surgery in a pooled
      analysis of randomized controlled trials. MATERIALS AND METHODS: A variety of
      sources were searched for randomized controlled trials evaluating the protective
      efficiency of WEPDs in gastrointestinal surgery. Subgroup analysis and meta
      regressions were conducted to investigate the possible influence of the type of
      WEPD on the size of intervention effect. This review was conducted in accordance
      with a prespecified protocol based on the guidance of the Cochrane Handbook and
      Preferred Reporting Items for Systematic Reviews and Meta-analyses statement.
      RESULTS: Sixteen studies with 3663 patients were included. The WEPDs usage led to
      a significant decrease in surgical wound infection (risk ratio [RR] = 0.64; 95%
      confidence interval [CI]: 0.46-0.87; P = 0.005; I2 = 63%), with the dual-ring
      design usage yielding a more significant reduction in surgical wound infection
      (RR = 0.24; 95% CI: 0.11-0.50; P = 0.0002; I2 = 29%), whereas the single-ring
      design usage yielding a nonsignificant result (RR = 0.78; 95% CI: 0.58-1.04; P =
      0.09; I2 = 53%). CONCLUSIONS: Double-ring WEPD, but not single-ring design,
      reduces wound infection rate significantly in gastrointestinal surgery.
      Therefore, the use of single-ring WEPD should be reconsidered.

PMID- 27884346
TI  - Survival outcomes of geriatric patients with clinically resectable gastric
      cancer: to operate or not.
AB  - BACKGROUND: Approximately, 50% of all gastric cancer patients are aged >70 y.
      Although curative surgery is the treatment of choice, many geriatric patients die
      of surgical complications. Therefore, we aimed to evaluate the impact of radical
      surgery on the survival outcome of geriatric patients with resectable gastric
      cancers. METHODS: About 488 patients diagnosed with resectable gastric cancers,
      aged >=70 y, between January 2007 and December 2012 at Chang Gung Memorial
      Hospital (CGMH) Linkou branch were included in this study. Using univariate and
      multivariate analyses, possible prognostic variables for survival outcome were
      assessed in 445 patients (91.2%) treated with radical surgery (operation [OP]
      group) and 43 (8.8%) receiving conservative treatment (non-OP group). The impact
      of radical surgery on survival outcomes was evaluated according to CGMH scores.
      RESULTS: On multivariate analysis, surgical resection with subtotal gastrectomy
      and CGMH score were the only independent prognostic factors for both overall and
      cancer-specific survival. The median survival time was 43 mo for the entire
      cohort. The OP group had significantly better survival outcome than the non-OP
      group (median survival, 50.3 versus 16.2 mo, P < 0.001). The median survival
      times for patients with CGMH scores <=20 were 64.1 and 20.0 mo (P < 0.002) and
      those for patients with CGMH scores >20 were 13.8 and 10.4 mo (P = 0.18) in the
      OP and non-OP groups, respectively. CONCLUSIONS: Surgical resection and CGMH
      score are independent prognostic factors for overall and cancer-specific
      survival; the CGMH score might be a prognostic indicator of surgical outcome in
      geriatric patients with resectable gastric cancers.

PMID- 27884347
TI  - Fabrication of three-dimensional scan-to-print ear model for microtia
      reconstruction.
AB  - BACKGROUND: Microtia is a congenital deformity of the external ear that occurs in
      1 of every 5000 births. Microtia reconstruction using traditional two-dimensional
      templates does not provide highly detailed ear shapes. Here, we describe the
      feasibility of using a three-dimensional (3D) ear model as a reference. MATERIALS
      AND METHODS: Seven children aged from 11 to 16 (6 grade III and 1 grade II
      microtia) were recruited from Seoul National University Children's Hospital,
      Korea. We generated 3D-computer-aided design models of each patient's ear by
      performing 3D laser scanning for a mirror-transformed cast of their normal ear.
      The 3D-printed ear model was used in microtia reconstruction surgery following
      the Nagata technique, and its shape was compared with the casted ear model.
      RESULTS: One patient experienced irritation caused by accidently pouring resin
      into the external auditory meatus, and another had minor skin necrosis; both
      complications were successfully treated. The average percentage differences of
      the superior, inferior, anterior, posterior, and lateral views between the casted
      and 3D-printed ear models were 1.17%, 1.48%, 1.64%, 1.80%, and 5.44%,
      respectively (average: 2.31%), where the difference between the casted ear models
      and traditional two-dimensional templates were 16.03% in average. CONCLUSIONS:
      Our results show that simple microtia reconstruction can be performed using 3D
      ear models. The 3D-printed ear models of each patient were consistent and
      accurately represented the thickness, depth, and height of the normal ear. The
      availability of the 3D-printed ear model in the operating room reduced the amount
      of unnecessary work during surgery.

PMID- 27884349
TI  - Endotoxemia accelerates diaphragm dysfunction in ventilated rabbits.
AB  - BACKGROUND: Ventilators may induce diaphragm dysfunction, and most of the septic
      population who are admitted to the intensive care unit require mechanical
      ventilation. However, there is no evidence that sepsis accelerates the onset of
      ventilator-induced diaphragm dysfunction or affects the microcirculation. Our
      study investigated whether lipopolysaccharide (LPS)-induced endotoxemia
      accelerated diaphragm dysfunction in ventilated rabbits by evaluating
      microcirculation, lipid accumulation, and diaphragm contractility. METHODS: After
      anesthesia and tracheostomy, 25 invasively monitored and mechanically ventilated
      New Zealand white rabbits were randomized to control (n = 5), controlled
      mechanical ventilation (CMV) (n = 5), pressure support ventilation (PSV; n = 5),
      CMV or PSV with LPS-induced endotoxemia (CMV-LPS and PSV-LPS, respectively; n = 5
      for each). Rabbits were anesthetized and ventilated for 24 h, except the control
      rabbits (30 min). Diaphragmatic contractility was evaluated using neuromechanical
      and neuroventilatory efficiency. We evaluated the following at the end of the
      protocol: (1) diaphragm microcirculation; (2) lipid accumulation; and (3)
      diaphragm muscular fibers structure. RESULTS: Diaphragm contractility,
      microcirculation, lipid accumulation, and fiber structures were severely
      compromised in endotoxemic animals after 24 h compared to nonendotoxemic rabbits.
      Moreover, a slight but significant increase in lipid accumulation was observed in
      CMV and PSV groups compared with controls (P < 0.05). CONCLUSIONS: Endotoxemia
      accelerates the diaphragm dysfunction process in ventilated rabbits, affects the
      microcirculation, and results in diaphragmatic lipid accumulation and
      contractility impairment.

PMID- 27884348
TI  - Prognostic relevance of hematological profile before resection for colorectal
      liver metastases.
AB  - BACKGROUND: Although alterations of hematological profile and especially elevated
      platelet counts were reported to influence survival in primary colorectal cancer,
      its prognostic relevance before the surgical treatment of colorectal liver
      metastases (CLM) is mainly unclear. Therefore, the aim of this study was to
      analyze the impact of these factors on overall survival following liver resection
      of CLM. MATERIALS AND METHODS: The surgical treatment of primary CLM between 1994
      and 2012 in 983 patients was retrospectively analyzed using univariable and
      multivariable Cox regression models. RESULTS: In the multivariable analyses, a
      preoperative anemia was independently associated with inferior overall outcome (P
      = 0.005, hazard ratio: 1.355). However, with only 2.7% of all cases, an elevation
      of preoperative platelets was not a frequent finding and no independent impact on
      survival (P = 0.834). Furthermore, abnormal hemoglobin and platelet values had no
      impact on rate of surgical revisions due to bleeding complications (P = 0.962 and
      P = 0.671, respectively), but a potential interaction between abnormal hemoglobin
      and platelet values and the amount of transfused packed red blood cells (P =
      0.004 and P < 0.001, respectively) was observed. CONCLUSIONS: Preoperative anemia
      is statistically significantly associated with inferior overall survival
      following resection of CLM and might define a new prognostic marker. Preoperative
      elevated platelets were not a frequent finding and showed no influence on overall
      survival.

PMID- 27884350
TI  - Roux-en-Y gastric bypass augments the feeding responses evoked by gastrin
      releasing peptides.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) is the most effective method for the
      treatment of obesity, and metabolic disease RYGB may reduce body weight by
      altering the feeding responses evoked by the short-term satiety peptides.
      MATERIALS AND METHODS: Here, we measured meal size (MS, chow), intermeal interval
      (IMI) length, and satiety ratio (SR, IMI/MS; food consumed per a unit of time) by
      the small and the large forms of gastrin-releasing peptide (GRP) in rats, GRP-10
      and GRP-29 (0, 0.1, 0.5 nmol/kg) infused in the celiac artery (CA, supplies
      stomach and upper duodenum) and the cranial mesenteric artery (CMA, supplies
      small and large intestine) in an RYGB rat model. RESULTS: GRP-10 reduced MS,
      prolonged the IMI, and increased the SR only in the RYGB group, whereas GRP-29
      evoked these responses by both routes and in both groups. CONCLUSIONS: The RYGB
      procedure augments the feeding responses evoked by exogenous GRP, possibly by
      decreasing total food intake, increasing latency to the first meal, decreasing
      number of meals or altering the sites of action regulating MS and IMI length by
      the two peptides.

PMID- 27884351
TI  - In vivo imaging of antioxidant response element activity during liver
      regeneration after partial hepatectomy.
AB  - BACKGROUND: The nuclear factor-erythroid 2-related factor 2 (Nrf2) -antioxidant
      response element (ARE) pathway is important for the regulation of antioxidative
      stress response and detoxification. To activate the expression of its target
      genes, such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone) 1
      (NQO1), Nrf2 binds to the ARE within the promoter region of these genes. Partial
      hepatectomy and consecutive liver regeneration lead to oxidative stress with
      activation of the Nrf2-ARE pathway. The aim of this study was to investigate ARE
      activity in vivo during liver regeneration after partial hepatectomy. MATERIALS
      AND METHODS: Transgenic ARE-luc mice were used. In these mice, the luciferase
      reporter gene is under the control of an ARE promoter element. Following 2/3
      partial hepatectomy (PHx), mice underwent in vivo bioluminescence imaging up
      until the ninth postoperative day. In addition, liver tissue was analyzed by
      immunohistochemistry (Nrf2 and HO-1), quantitative reverse transcription-PCR (HO
      1 and NQO1) and in vitro luminescence assays. RESULTS: Bioluminescence imaging
      revealed a significant increase in Nrf2-ARE activity after PHx. The signal
      maximum was recorded on the third day after PHx. Seven days postoperatively, the
      signal almost reached baseline levels. In immunohistochemistry, significantly
      more hepatocytes were positive for Nrf2 and HO-1 on the third postoperative day
      compared with baseline levels. The mRNA expression of HO-1 and NQO1 were
      significantly increased on day 3 as measured by qRT-PCR. CONCLUSIONS: This study
      demonstrated the time-dependent activation of the Nrf2-ARE system during liver
      regeneration in vivo. The transgenic ARE-luc mouse provided a convenient model
      for studying Nrf2-mediated gene expression noninvasively and may facilitate
      further experiments with therapeutic modulation of the antioxidative stress
      response.

PMID- 27884352
TI  - Timing of Coronary Invasive Strategy in Non-ST-Segment Elevation Acute Coronary
      Syndromes and Clinical Outcomes: An Updated Meta-Analysis.
AB  - OBJECTIVES: The aim of this study was to compare an early versus a delayed
      invasive strategy in non-ST-segment elevation acute coronary syndromes by
      performing a meta-analysis of all available randomized controlled clinical
      trials. BACKGROUND: An invasive approach is recommended to prevent death and
      myocardial infarction in non-ST-segment elevation acute coronary syndromes.
      However, the timing of angiography and the subsequent intervention, when
      required, remains controversial. METHODS: A previous meta-analysis of 7
      randomized clinical trials comparing early and delayed invasive strategies in non
      ST-segment elevation acute coronary syndromes with 3 new randomized clinical
      trials identified in a search of the published research (n = 10 trials, n = 6,397
      patients) was updated. RESULTS: The median time between randomization and
      angiography ranged from 0.5 to 14.0 h in the early group and from 18.3 to 86.0 h
      in the delayed group. There was no difference in the primary endpoint of
      mortality (4% vs. 4.7%; random-effects odds ratio [OR]: 0.85; 95% confidence
      interval [CI]: 0.67 to 1.09; p = 0.20; I2 = 0%). The rate of myocardial
      infarction was also similar (6.7% vs. 7.7%; random-effects OR: 0.88; 95% CI: 0.53
      to 1.45; p = 0.62; I2 = 77.5%). An early strategy was associated with a reduction
      in recurrent ischemia or refractory angina (3.8% vs. 5.8%; random-effects OR:
      0.54; 95% CI: 0.40 to 0.74; p < 0.01; I2 = 28%) and a shorter in-hospital stay
      (median 112 h [interquartile range: 61 to 158 h] vs. 168 h [interquartile range:
      90.3 to 192 h]; random-effects standardized mean difference -0.40; 95% CI: -0.59
      to -0.21; p < 0.01; I2 = 79%). Major bleeding was similar in the 2 groups (3.9%
      vs. 4.2%; random-effects OR: 0.94; 95% CI: 0.73 to 1.22; p = 0.64; I2 = 0%).
      CONCLUSIONS: An early invasive strategy does not reduce the risk for death or
      myocardial infarction compared with a delayed strategy. Recurrent ischemia and
      length of stay were significantly reduced with an early invasive strategy.

PMID- 27884353
TI  - Invasive Strategy After Non-ST-Segment Elevation Acute Coronary Syndrome: Timing
      and Controversies.

PMID- 27884355
TI  - Statistical Approaches to Composite Endpoints.

PMID- 27884354
TI  - Computing Methods for Composite Clinical Endpoints in Unprotected Left Main
      Coronary Artery Revascularization: A Post Hoc Analysis of the DELTA Registry.
AB  - OBJECTIVES: The study sought to investigate the impact of different computing
      methods for composite endpoints other than time-to-event (TTE) statistics in a
      large, multicenter registry of unprotected left main coronary artery (ULMCA)
      disease. BACKGROUND: TTE statistics for composite outcome measures used in ULMCA
      studies consider only the first event, and all the contributory outcomes are
      handled as if of equal importance. METHODS: The TTE, Andersen-Gill, win ratio
      (WR), competing risk, and weighted composite endpoint (WCE) computing methods
      were applied to ULMCA patients revascularized by percutaneous coronary
      intervention (PCI) or coronary artery bypass grafting (CABG) at 14 international
      centers. RESULTS: At a median follow-up of 1,295 days (interquartile range: 928
      to 1,713 days), all analyses showed no difference in combinations of death,
      myocardial infarction, and cerebrovascular accident between PCI and CABG. When
      target vessel revascularization was incorporated in the composite endpoint, the
      TTE (p = 0.03), Andersen-Gill (p = 0.04), WR (p = 0.025), and competing risk (p <
      0.001) computing methods showed CABG to be significantly superior to PCI in the
      analysis of 1,204 propensity-matched patients, whereas incorporating the clinical
      relevance of the component endpoints using WCE resulted in marked attenuation of
      the treatment effect of CABG, with loss of significance for the difference
      between revascularization strategies (p = 0.10). CONCLUSIONS: In a large study of
      ULMCA revascularization, incorporating the clinical relevance of the individual
      outcomes resulted in sensibly different findings as compared with the
      conventional TTE approach. In particular, using the WCE computing method, PCI and
      CABG were no longer significantly different with respect to the composite of
      death, myocardial infarction, cerebrovascular accident, or target vessel
      revascularization at a median of 3 years.

PMID- 27884357
TI  - If TAVR Cannot Be Transfemoral, Then What?

PMID- 27884356
TI  - Direct Comparison of Feasibility and Safety of Transfemoral Versus Transaortic
      Versus Transapical Transcatheter Aortic Valve Replacement.
AB  - OBJECTIVES: The aim of this study was to compare outcomes among transfemoral
      (TF), transaortic (TAo), and transapical (TA) transcatheter aortic valve
      replacement (TAVR). BACKGROUND: Very few studies have investigated the
      differences among TF, TAo, and TA TAVR in terms of safety and feasibility.
      METHODS: Between January 2011 and December 2014, 467 consecutive cases of TF
      TAVR, 289 cases of TAo TAVR, and 42 cases of TA TAVR were analyzed. Baseline
      characteristics, procedural characteristics, and outcomes were compared between
      TF and TAo and between TAo and TA approaches. RESULTS: Balloon-expandable
      prostheses were used in 320 cases of TF TAVR (69%), 209 cases of TAo TAVR (72%),
      and all cases of TA TAVR. The remaining cases were performed using self
      expandable prostheses. Patient age and Society of Thoracic Surgeons score were
      similar (83.8 years vs. 83.7 years vs. 81.3 years and 6.2% vs. 5.8% vs. 7.1%)
      among all groups. Although nonsignificant, a trend toward lower 30-day mortality
      (5% vs. 9%; p = 0.057) was observed with TF TAVR compared with TAo TAVR. Kaplan
      Meier analysis revealed a trend toward a higher 1-year survival rate (log-rank p
      = 0.067) with TF TAVR compared with TAo TAVR. There was no significant difference
      in 30-day mortality between TAo and TA TAVR (9% vs. 14%; p = 0.283). Kaplan-Meier
      analysis revealed a trend toward a higher 1-year survival rate (log-rank p =
      0.154) with TAo TAVR compared with TA TAVR. CONCLUSIONS: Although the 30-day
      mortality and 1-year survival rates were similar between TF and TAo TAVR
      patients, a trend in favor of the TF approach was observed. In addition, the TAo
      approach can be considered as an alternative to the TA approach when the TF
      approach seems unsuitable.

PMID- 27884359
TI  - From Good to Great: Raising the Bar on LAA Closure With Pre-Procedure CT
      Planning.

PMID- 27884358
TI  - Application of 3-Dimensional Computed Tomographic Image Guidance to WATCHMAN
      Implantation and Impact on Early Operator Learning Curve: Single-Center
      Experience.
AB  - OBJECTIVES: The aim of this study was to examine the impact of 3-dimensional (3D)
      computed tomographic (CT) guided procedural planning for left atrial appendage
      (LAA) occlusion on the early operator WATCHMAN learning curve. BACKGROUND:
      Traditional WATCHMAN implantation is dependent on 2-dimensional transesophageal
      echocardiographic (TEE) sizing and intraprocedural guidance. METHODS: LAA
      occlusion with the WATCHMAN device was performed in 53 patients. Pre-procedural
      case plans were generated from CT studies with recommended device size, catheter
      selection, and C-arm angle for deployment. RESULTS: All 53 patients underwent
      successful LAA occlusion with the WATCHMAN. Three-dimensional CT LAA maximal
      width sizing was 2.7 +/- 2.2 mm and 2.3 +/- 3.0 mm larger than 2-dimensional and
      3D TEE measurements, respectively (p <= 0.0001). By CT imaging, device selection
      was 100% accurate. There were 4 peri-WATCHMAN leaks (<4.5 mm) secondary to
      accessory LAA pedunculations. By 2-dimensional TEE maximal-width measurements
      alone, 62.3% (33 of 53) would have required larger devices. Using 3D TEE maximal
      width measurements, 52.8% of cases (28 of 53) would have required larger devices.
      Three-dimensional TEE length would have inappropriately excluded 10 patients from
      WATCHMAN implantation. Compared with the average of 1.8 devices used per
      implantation attempt in PROTECT AF (WATCHMAN Left Atrial Appendage System for
      Embolic Protection in Patients With Atrial Fibrillation) (82% success rate), the
      present site averaged 1.245 devices per implantation attempt (100% success rate).
      There were no intraprocedural screen failures and no major adverse cardiac
      events. CONCLUSIONS: Three-dimensional CT image case planning provides a
      comprehensive and customized patient-specific LAA assessment that appears to be
      accurate and may possibly facilitate reducing the early WATCHMAN implantation
      learning curve.

PMID- 27884360
TI  - Cost-Effectiveness of Endovascular Femoropopliteal Intervention Using Drug-Coated
      Balloons Versus Standard Percutaneous Transluminal Angioplasty: Results From the
      IN.PACT SFA II Trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of drug
      coated balloon (DCB) angioplasty versus standard percutaneous transluminal
      angioplasty (PTA). BACKGROUND: Recent trials have reported lower rates of target
      lesion revascularization with DCB angioplasty versus standard PTA. However, the
      cost-effectiveness of DCB angioplasty is unknown. METHODS: A prospective economic
      study was performed alongside the IN.PACT SFA II (IN.PACT Admiral Drug-Coated
      Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral
      Artery [SFA] and Proximal Popliteal Artery [PPA]) trial, which randomized 181
      patients with femoropopliteal disease to the IN.PACT DCB versus standard PTA.
      Resource use data were collected over 2-year follow-up, and costs were assigned
      using resource-based accounting and billing data. Health utilities were assessed
      using the EuroQol 5-dimensions questionnaire. Cost-effectiveness was assessed as
      cost per quality-adjusted life-year (QALY) gained using a decision-analytic model
      on the basis of empirical data from the trial assuming identical long-term
      mortality. RESULTS: Initial costs were $1,129 per patient higher with DCB
      angioplasty than standard PTA, driven by higher costs for the DCB itself. Between
      discharge and 24 months, target limb-related costs were $1,212 per patient lower
      with DCB angioplasty such that discounted 2-year costs were similar for the 2
      groups ($11,277 vs. $11,359, p = 0.97), whereas QALYs tended to be greater among
      patients treated with DCBs (1.53 +/- 0.44 vs. 1.47 +/- 0.42, p = 0.40). The
      probability that DCB angioplasty is cost-effective compared with standard PTA was
      70% using a threshold of $50,000 per QALY gained and 79% at a threshold of
      $150,000 per QALY gained. CONCLUSIONS: For patients with femoropopliteal disease,
      DCB angioplasty is associated with better 2-year outcomes and similar target limb
      related costs compared with standard PTA. Formal cost-effectiveness analysis on
      the basis of these results suggests that use of the DCB angioplasty is likely to
      be economically attractive.

PMID- 27884361
TI  - The Price Is Right (But Buyer Beware).

PMID- 27884362
TI  - E-CART (ElectroCautery-Assisted Re-enTry) of an Aorto-Ostial Right Coronary
      Artery Chronic Total Occlusion: First-in-Man.

PMID- 27884363
TI  - Fibromuscular Dysplasia Presented With Spontaneous Dissection of the Left Main
      Artery.

PMID- 27884364
TI  - Guiding Light: Insights Into Atherectomy by Optical Coherence Tomography.

PMID- 27884365
TI  - Cigarette Smoking, Clopidogrel Responsiveness, and Hemoglobin Level.

PMID- 27884366
TI  - Reply: Cigarette Smoking, Clopidogrel Responsiveness, and Hemoglobin Level.

PMID- 27884367
TI  - Antithrombotic Regimen in Post-TAVR Atrial Fibrillation: Not an Easy Decision.

PMID- 27884369
TI  - An Open Letter to My Successor.

PMID- 27884368
TI  - Reply: Antithrombotic Regimen in Post-TAVR Atrial Fibrillation: Not an Easy
      Decision.

PMID- 27884370
TI  - The allure of a simple story.

PMID- 27884371
TI  - Committing to disability inclusion to end AIDS by 2030.

PMID- 27884372
TI  - GBD 2015 and HIV estimates from the Optima model.

PMID- 27884373
TI  - GBD 2015 and HIV estimates from the Optima model - Authors' reply.

PMID- 27884374
TI  - Obstacles to prescribers' initiation early antiretroviral therapy: a barrier to
      achieving 90-90-90 goals.

PMID- 27884375
TI  - The inflammasome: Friend or foe in Chlamydia infection?
AB  - In this issue of the Biomedical Journal, we take a look at the still somewhat
      perplexing role of the inflammasome in Chlamydia infection. We also highlight
      findings suggesting a link between structural changes to arteries in the brain
      and the onset of depression. Finally, we learn about some of the implications of
      co-morbidity between diabetes and infectious diseases.

PMID- 27884376
TI  - Purinergic signaling in infection and autoimmune disease.
AB  - Purinergic signaling plays a key role in inflammatory processes and modulates
      immune responses against a variety of bacterial and eukaryotic parasites. Here we
      highlight the role of purinergic receptor activation in infection and autoimmune
      diseases. Purinergic signaling and inflammasomes modulate the host immune
      response against chlamydial infections. In addition, increasing evidence suggests
      that purinergic signaling contributes to Schistosomiasis morbidity, a neglected
      tropical disease caused by parasitic worms called schistosomes. Finally, the P2X7
      receptor and NLRP3 inflammasome have been described to be involved in the
      pathogenesis of systemic lupus erythematosus, suggesting that these signaling
      pathways as suitable therapeutic targets for management and treatment of
      different immune diseases.

PMID- 27884377
TI  - Danger signals, inflammasomes, and the intricate intracellular lives of
      chlamydiae.
AB  - Chlamydiae are obligate intracellular bacterial pathogens, and as such are
      sensitive to alterations in the cellular physiology of their hosts. Chlamydial
      infections often cause pathologic consequences due to prolonged localized
      inflammation. Considerable advances have been made in the last few years
      regarding our understanding of how two key inflammation-associated signaling
      pathways influence the biology of Chlamydia infections: inflammation regulating
      purinergic signaling pathways significantly impact intracellular chlamydial
      development, and inflammasome activation modulates both chlamydial growth and
      infection mediated pro-inflammatory cytokine production. We review here elements
      of both pathways, presenting the latest developments contributing to our
      understanding of how chlamydial infections are influenced by inflammasomes and
      purinergic signaling.

PMID- 27884378
TI  - Purinergic signaling in schistosomal infection.
AB  - Human schistosomiasis is a chronic inflammatory disease caused by blood fluke
      worms belonging to the genus Schistosoma. Health metrics indicate that the
      disease is related to an elevated number of years lost-to-disability and years
      lost-to-life. Schistosomiasis is an intravascular disease that is related to a
      Th1 and Th2 immune response polarization, and the degree of polarization affects
      the outcome of the disease. The purinergic system is composed of adenosine and
      nucleotides acting as key messenger molecules. Moreover, nucleotide-transforming
      enzymes and cell-surface purinergic receptors are obligatory partners of this
      purinergic signaling. In mammalian cells, purinergic signaling modulates innate
      immune responses and inflammation among other functions; conversely purinergic
      signaling may also be modulated by inflammatory mediators. Moreover, schistosomes
      also express some enzymes of the purinergic system, and it is possible that worms
      modulate host purinergic signaling. Current data obtained in murine models of
      schistosomiasis support the notion that the host purinergic system is altered by
      the disease. The dysfunction of adenosine receptors, metabotropic P2Y and
      ionotropic P2X7 receptors, and NTPDases likely contributes to disease morbidity.

PMID- 27884380
TI  - Association of endothelial dysfunction and cytotoxin-associated gene A-positive
      Helicobacter pylori in patients with cardiac syndrome X.
AB  - BACKGROUND: Existence of coronary endothelial dysfunction has been demonstrated
      in patients with cardiac syndrome X (CSX). In addition, Helicobacter pylorus (H.
      pylori) has been associated with CSX. We aimed to assess the possible association
      of endothelial dysfunction and cytotoxin-associated gene A-positive H. pylori
      (CagA+) infection in CSX patients. METHODS: Fifty-six patients with CSX (23
      male/33 female; age: 51.25 +/- 8.86 years) who were anti-H. pylori IgG-positive
      [H. pylori(+)] and 24 CSX patients (7 male/17 female; age: 52.79 +/- 9.88 years)
      who were H. pylori(-) were included. Also, anti-H. pylori IgG-positive patients
      were determined by the presence of IgG antibody to CagA. Levels of endothelin-1
      (ET-1), E-selectin and intercellular adhesion molecule-1 (ICAM-1) were measured.
      RESULTS: Endothelial dysfunction biomarkers were higher in H. pylori(+) than in
      H. pylori(-) patients (ET-1: 54.60 +/- 25.39 vs. 42.59 +/- 18.37 pg/ml, p = 0.04;
      E-selectin: 42.68 +/- 14.26 vs. 31.72 +/- 8.26 ng/ml, p = 0.001; ICAM-1: 339.68
      +/- 135.8 vs. 266.51 +/- 125.1 ng/ml, p = 0.02). Among H. pylori(+) subjects, 28
      cases were CagA(+) and 28 cases were CagA(-). There were significant differences
      in measured levels of E-selectin between CagA(+) and CagA(-) groups (48.00 +/-
      16.37 vs. 37.37 +/- 9.37 ng/ml, p = 0.004). For ET-1 and ICAM-1 levels, the
      difference between CagA(+) and CagA(-) was insignificant (p = 0.174 and p = 0.07,
      respectively). CONCLUSION: High levels of endothelial dysfunction biomarkers are
      found in CSX patients with anti-CagA(+). These findings suggest the infection
      with CagA(+) H. pylori strain may play a role as a risk factor in development of
      CSX through provocation of endothelial dysfunction. Therefore, a long term follow
      up to investigate the outcomes of these patients is proposed.

PMID- 27884381
TI  - Elevated adiponectin but varied response in circulating leptin levels to
      falciparum malaria in type 2 diabetics and non-diabetic controls.
AB  - BACKGROUND: To investigate effects of falciparum malaria on circulating levels of
      leptin and adiponectin in type 2 diabetes mellitus (T2DM) and non-diabetic
      controls in relation to measures of adiposity. METHODS: Levels of leptin and
      adiponectin were measured in 100 type 2 diabetics and 100 age-matched controls
      before and during falciparum malaria in a 2-year prospective study. Also, waist
      circumference (WC), weight, height and hip circumference were measured. Body mass
      index (BMI) and waist-to-hip ratio (WHR) were computed. RESULTS: At baseline,
      diabetics had significantly (p < 0.05) higher WC and BMI but lower WHR, leptin
      and adiponectin levels. Baseline leptin correlated positively with WC (r = 0.633;
      p < 0.001) and BMI (r = 0.63; p < 0.001) in diabetics but only BMI (0.562; p <
      0.001) in non-diabetic controls. Baseline leptin and adiponectin correlated
      positively (r = 0.249; p = 0.029) in non-diabetic respondents only. Adiponectin
      correlated negatively with WC (r = -0.58; p = 0.006) in diabetic males only.
      During malaria, mean levels of leptin and adiponectin were comparable (p > 0.05)
      between diabetics and controls. However, compared to baseline levels, significant
      (p < 0.001) elevation of adiponectin was found in both study groups. In respect
      of leptin, significant (p < 0.001) rise but decline was observed in diabetics and
      controls respectively. Malaria-induced leptin correlated negatively with
      adiponectin (r = -0.694; p < 0.001) in non-diabetic controls only. CONCLUSION:
      Diabetics and controls exhibited increased adiponectin levels due to falciparum
      malaria but differed in response in terms of leptin levels.

PMID- 27884382
TI  - Profile of glycated-hemoglobin, antioxidant vitamin and cytokine levels in
      pulmonary tuberculosis patients: A cross sectional study at Pulmonary Diseases
      Center Semarang City, Indonesia.
AB  - BACKGROUND: Uncontrolled blood glucose, which marked by high level of HbA1c,
      increases risk of pulmonary TB because of cellular immunity dysfunction. This
      study aimed to analyze profile of glycated hemoglobin, antioxidant vitamins
      status and cytokines levels in active pulmonary TB patients. METHODS: This was a
      cross sectional study, conducted at Pulmonary Diseases Center Semarang City,
      Indonesia. Study subject consisted of 62 pulmonary TB patients, diagnosed with
      positive acid fast bacilli and chest X-ray. ELISA was used to measure IFN-gamma
      and IL-12. Status of antioxidant vitamins was determined by concentration of
      vitamin A and E using HPLC. Blood glucose control was determined by HbA1c
      concentration (HbA1c >=7% is considered as uncontrolled). RESULTS: A significant
      difference of age between pulmonary tuberculosis patients with normal and
      uncontrolled blood glucose (p = 0.000) was showed, while all other
      characteristics (sex, education, occupation) did not differ with p = 0.050,
      0.280, 0.380 respectively. Mean HbA1c was 7.25 +/- 2.70%. Prevalence of
      uncontrolled glucose among pulmonary TB patients was 29%. Levels of IFN-gamma and
      IL-12 did not differ according to HbA1c concentration (p = 0.159 and p = 0.965
      respectively). Pulmonary tuberculosis patients with uncontrolled blood glucose
      has higher vitamin E (p = 0.006), while vitamin A did not differ significantly (p
      = 0.478). CONCLUSIONS: This study supports the importance of performing diabetes
      screening among pulmonary TB patients. Further study needs to be done to
      determine the feasibility of TB-DM co-management.

PMID- 27884383
TI  - Histomorphometric study of basilar artery in normal and suicide persons.
AB  - BACKGROUND: Depression in association with cerebro-vascular risk factors and
      white matter lesions is increasingly referred to as 'vascular depression'. There
      are several brain areas known for playing a role in patho-physiology of
      depression which may lead to suicidal tendencies, are fed by basilar artery.
      Therefore, the arterial histoarchitecture was studied in the normal and suicide
      individuals to establish a relationship between the vascular structural changes
      and depression. METHODS: 40 post-mortem samples (both sexes) of basilar artery
      have been collected and were grouped into normal and suicide groups. Samples were
      measured for arterial, lumen diameter and the thickness of tunica intima, media
      and adventitia using H & E stained sections. While, Orcein stained sections were
      used to estimate the volume fraction of elastic fibres, and Van Gieson stained
      sections to estimate the volume fraction of collagen fibres. RESULTS: The mean
      thickness of tunica media of basilar artery in suicide individuals (1.08 microns)
      showed a statistically significant decrease when compared to normal person (1.33
      microns). Further, volume fraction of collagen (0.06 mm3/mm3) and elastic fibres
      (0.06 mm3/mm3) in suicide persons showed a statistically significant decrease
      when compared to normal person (collagen fibres 0.08 mm3/mm3; elastic fibres 0.09
      mm3/mm3). CONCLUSIONS: This study establishes a probable causative relationship
      between vascular structural abnormality and depression which may drive the
      individual to commit suicide.

PMID- 27884384
TI  - Radiographic outcome of necrotic immature teeth treated with two endodontic
      techniques: A retrospective analysis.
AB  - BACKGROUND: The endodontic treatment of teeth with immature root has always been
      a challenge. To achieve a better prognosis, regenerative endodontic treatment may
      become a treatment trend for teeth with apical periodontitis and immature roots.
      METHODS: Clinical and radiographic data were collected from 38 endodontic treated
      immature teeth (21 apexification and 17 regeneration). Measure the radiographic
      outcome by quantifying the apical lesion. RESULTS: There was no statistical
      difference between the two treatments regarding PAI scores at the 1-, 3-, 6-, and
      12-month follow-up (p > 0.05). In addition, different operators and the different
      stages of root development for both techniques showed no significant statistical
      difference on the final treatment results. CONCLUSIONS: In this study, assessment
      of the radiographic outcomes indicated that regenerative endodontic treatment
      were identical to the apexification technique.

PMID- 27884379
TI  - Purinergic signalling in autoimmunity: A role for the P2X7R in systemic lupus
      erythematosus?
AB  - Purinergic signalling plays a crucial role in immunity and autoimmunity. Among
      purinergic receptors, the P2X7 receptor (P2X7R) has an undisputed role as it is
      expressed to high level by immune cells, triggers cytokine release and modulates
      immune cell differentiation. In this review, we focus on evidence supporting a
      possible role of the P2X7R in the pathogenesis of systemic lupus erythematosus
      (SLE).

PMID- 27884385
TI  - Anecdotes: Ode to dentistry II.

PMID- 27884386
TI  - Preseptal and orbital cellulitis.

PMID- 27884387
TI  - Initial results of the National Registry of Incisional Hernia.
AB  - INTRODUCTION: The aim of this study was to the data from the National Registry of
      Incisional Hernia (EVEREG) to determine the reality of the treatment of this
      condition in Spain. METHODS: EVEREG is an online prospective database which has
      been functioning since July 2012; operations for incisional hernia are
      anonymously recorded. RESULTS: Up to March 2015, 4501 hernias from 95 of the 113
      participating hospitals were registered. The mean age of the patients was 62.7,
      and 56.5% were women, with a mean BMI of 30.2kg/m2; 29.8% presented a high
      surgical risk (ASA III-V). A total of 93.7% were scheduled surgeries, 88.3% open
      surgery and 22.2% were recurrent incisional hernias. There were 66.9% hernias
      after a midline laparotomy, and 81.4% of a transverse diameter of less than 10cm.
      A mesh was used in 96.2% of cases. Postoperative stay was 5.3 days and 29.1%
      presented a complication, with a mortality of 0.8%. After a median follow-up of
      7.7 months a high rate of recurrence was detected (20.7% per year), especially in
      hernias that were operated on after a previous repair (18.1% primary vs. 30.6%
      recurrent; P=.004). CONCLUSION: the EVEREG registry is a useful tool to know the
      current situation of incisional hernia treatment. Analysis of the data shows
      several points that could be improved: a low rate of follow-up and high
      recurrence rate.

PMID- 27884388
TI  - Shaped-bolus protocol reduces contrast medium volume in abdominal CT while
      maintaining image quality.
AB  - AIM: To prospectively assess whether bolus shaping to exponentially decrease the
      contrast medium injection rate leads to alteration in image validity or renal
      function. MATERIALS AND METHODS: In this prospective study, patients
      alternatively received 100 ml contrast medium versus 75 ml via bolus shaping.
      Image quality was assessed via measurement of attenuation values in the aorta,
      liver, and spleen and also blinded subjective assessment of image sharpness, low
      contrast detectability, image noise, and overall quality. Renal function was
      assessed by change in creatinine levels up to 72 hours post-contrast medium
      administration. RESULTS: Of 190 abdominal computed tomography (CT) studies
      performed in the 3-month period, 98 received the 75 ml dose. There was no
      significant difference in renal function or objective image quality with a
      significant improvement in image sharpness in the 100 ml group. CONCLUSIONS: By
      using bolus-shaping software, it is possible to maintain objective image quality
      while reducing the contrast medium load to the patient. This has significant
      implications regarding clinical practice in decreasing cost and risks associated
      with iodinated contrast media.

PMID- 27884389
TI  - Omega 3 fatty acids for the treatment of dementia: a Cochrane review summary.

PMID- 27884390
TI  - Meeting the workforce challenges for older people living with cancer.

PMID- 27884391
TI  - Basic airway skills acquisition using the American College of
      Surgeons/Association for Surgical Education medical student simulation-based
      surgical skills curriculum: Initial results.
AB  - BACKGROUND: The ACS/ASE Medical Student Simulation-Based Skills Curriculum was
      developed to standardize medical student training. This study aims to evaluate
      the feasibility and validity of implementing the basic airway curriculum.
      METHODS: This single-center, prospective study of medical students participating
      in the basic airway module from 12/2014-3/2016 consisted of didactics, small
      group practice, and testing in a simulated clinical scenario. Proficiency was
      determined by a checklist of skills (1-15), global score (1-5), and letter grade
      (NR-needs review, PS-proficient in simulation scenario, CP-proficient in clinical
      scenario). A proportion of students completed pre/post-test surveys regarding
      experience, satisfaction, comfort, and self-perceived proficiency. RESULTS: Over
      16 months, 240 students were enrolled with 98% deemed proficient in a simulated
      or clinical scenario. Pre/post-test surveys (n = 126) indicated improvement in
      self-perceived proficiency by 99% of learners. All students felt moderately to
      very comfortable performing basic airway skills and 94% had moderate to
      considerable satisfaction after completing the module. CONCLUSIONS: The ACS/ASE
      Surgical Skills Curriculum is a feasible and effective way to teach medical
      students basic airway skills using simulation.

PMID- 27884392
TI  - Robust stabilization of underactuated nonlinear systems: A fast terminal sliding
      mode approach.
AB  - This paper presents a fast terminal sliding mode based control design strategy
      for a class of uncertain underactuated nonlinear systems. Strategically, this
      development encompasses those electro-mechanical underactuated systems which can
      be transformed into the so-called regular form. The novelty of the proposed
      technique lies in the hierarchical development of a fast terminal sliding
      attractor design for the considered class. Having established sliding mode along
      the designed manifold, the close loop dynamics become finite time stable which,
      consequently, result in high precision. In addition, the adverse effects of the
      chattering phenomenon are reduced via strong reachability condition and the
      robustness of the system against uncertainties is confirmed theoretically. A
      simulation as well as experimental study of an inverted pendulum is presented to
      demonstrate the applicability of the proposed technique.

PMID- 27884393
TI  - 1,25-Dihydroxyvitamin D3 targeting VEGF pathway alleviates house dust mite (HDM)
      induced airway epithelial barrier dysfunction.
AB  - BACKGROUND: In our previous studies, we have indentified that 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) can alleviate toluene diisocyanate-induced
      airway epithelial barrier disruption and we also found that vascular endothelial
      growth factor (VEGF) derived from airway epithelials cells could disrupt
      epithelial barrier. OBJECTIVE: The study aimed to investigate whether 1,25(OH)2D3
      can inhibit house dust mite (HDM) induced airway epithelial barrier dysfunction
      by regulating the VEGF pathway. METHOD: The 16HBE and BEAS-2B cells were cultured
      and treated according to the experiment requirement. Trans Epithelial Electric
      Resistance (TEER), permeability of epithelial layer, and distribution and
      expression of junction proteins were used to evaluate the cell layer barrier
      function, Western Blot was used to evaluate the expression of junction proteins
      and phosphorylated Akt in the cells, RT-PCR and ELISA were used to evaluate the
      VEGF gene expression and protein release in the cells. Recombinant VEGF165 was
      used to determine the role of the VEGF pathway in the epithelial barrier
      function. RESULTS: HDM resulted in a decline in TEER and increase of cell
      permeability, following abnormal distribution and expression of junction proteins
      (E-Cadherin and zona occludens (ZO)-1), accompanied by a significant upregulation
      of VEGF and phosphorylated Akt, which were all partly recovered by treatment with
      either 1,25(OH)2D3 or PI3K inhibitor LY294002. VEGF165-induced barrier
      dysfunction was accompanied by disruption of the epithelial E-cadherin and beta
      catenin, pretreatment of 1,25(OH)2D3 and LY294002 markedly attenuated VEGF
      induced airway barrier disruption in 16HBE cells. CONCLUSION: 1,25(OH)2D3 can
      alleviate HDM-induced airway epithelial barrier dysfunction by inhibiting PI3K
      pathway-dependent VEGF release.

PMID- 27884394
TI  - [Mitomycin-induced pulmonary veno-occlusive disease: A rare but severe
      complication].

PMID- 27884395
TI  - Adaptive cultural transmission biases in children and nonhuman primates.
AB  - Comparative and evolutionary developmental analyses seek to discover the
      similarities and differences between humans and non-human species that might
      illuminate both the evolutionary foundations of our nature that we share with
      other animals, and the distinctive characteristics that make human development
      unique. As our closest animal relatives, with whom we last shared common
      ancestry, non-human primates have been particularly important in this endeavour.
      Such studies have focused on social learning, traditions, and culture, and have
      discovered much about the 'how' of social learning, concerned with key underlying
      processes such as imitation and emulation. One of the core discoveries is that
      the adaptive adjustment of social learning options to different contexts is not
      unique to human, therefore multiple new strands of research have begun to focus
      on more subtle questions about when, from whom, and why such learning occurs.
      Here we review illustrative studies on both human infants and young children and
      on non-human primates to identify the similarities shared more broadly across the
      primate order, and the apparent specialisms that distinguish human development.
      Adaptive biases in social learning discussed include those modulated by task
      comprehension, experience, conformity to majorities, and the age, skill,
      proficiency and familiarity of potential alternative cultural models.

PMID- 27884397
TI  - Corrigendum to "BCL11A expression in acute phase chronic myeloid leukemia" [Leuk.
      Res. 47 (2016) 88-92].

PMID- 27884396
TI  - Effects of visfatin on the apoptosis of intestinal mucosal cells in immunological
      stressed rats.
AB  - This study was undertaken to determine if visfatin is involved in the
      inflammation or apoptosis introduced by LPS in rats. Forty 8-week old Wistar rats
      were divided into four groups (n=10 in each group) and injected with saline,
      visfatin, LPS and visfatin+LPS co-stimulated via caudal vein. The duodenum,
      jejunum and ileum were harvested from all the rats. Compared to the saline
      treated group, visfatin significantly increased the number of TUNEL-positive
      apoptotic cells and the expression of caspase-3 protein in intestinal mucosa.
      Similarly, ELISA and western blot analysis also showed the up-regulation of pro
      caspase-3 and cleaved caspase-3 expression in the visfatin group compared to the
      control group. In contrast to LPS, visfatin down-regulated the expression of
      cleaved-caspase-3 in the visfatin+LPS co-stimulated group, resulting in a
      significant decrease in apoptosis in intestinal mucosal cells. We observed more
      pro-caspase-3 positive cells in the visfatin+LPS co-stimulated group. The results
      indicate that, in the presence of LPS, visfatin plays an important role in the
      regulation of cell apoptosis and inflammation.

PMID- 27884400
TI  - Stephen Jay Gould and the Value of Neutrality of Science During the Cold War.
AB  - Stephen Jay Gould was a paleontologist and scientific celebrity at the close of
      the twentieth century, most famous for his popular writings on evolution and his
      role in the American creationist controversies of that era. In the early 1980s,
      Gould was drawn into the "nuclear winter" episode through his friendship with
      Carl Sagan, an astronomer and popular science celebrity. Sagan helped develop the
      theory of nuclear winter and subsequently used the theory as evidence to petition
      the United States government to scale back its nuclear armament. The theory of
      nuclear winter claimed that even a small nuclear exchange could result in a
      atmospheric blackening akin to the extinction event of the late Cretaceous. Gould
      was not a climate scientist but he testified before the U.S. House of
      Representatives as an expert on historical extinction events. Gould's insistence
      on the value-neutrality of nuclear winter reveals much about the moral politics
      of science in late Cold War America. Coming at the heels of leftist scientific
      activism of the 1980s, the nuclear winter episode demonstrates how value
      neutrality emerged the salient feature of scientific involvement in American
      politics in this period.

PMID- 27884399
TI  - Cardiovascular events and death in Japanese patients with chronic kidney disease.
AB  - The incidence of cardiovascular disease (CVD) is higher in patients with chronic
      kidney disease (CKD) than in the general population, and the risk of CVD
      increases with reductions in renal function. However, the incidence of CVD in
      Japanese patients with CKD has not been sufficiently investigated. To measure
      this we conducted the Chronic Kidney Disease Japan Cohort (CKD-JAC) Study over
      four years in 2,966 Japanese patients with CKD to examine the incidence of CVD
      and all-cause death. These patients had an estimated glomerular filtration rate
      (eGFR) of 10-59 ml/min/1.73 m2, were under nephrologist care, and pooled from 17
      medical institutions in Japan. At the median follow-up of 3.9 years, 69 patients
      had died, 217 had cardiovascular events, and 514 started maintenance dialysis
      therapy. The incidences of cardiovascular events were 11.9, 19.1, 25.0, and 39.4
      per 1,000 person-years at eGFRs of 45-59, 30-44, 15-29, and under 15 ml/min/1.73
      m2, respectively. The adjusted Cox proportional hazards models showed that the
      risk of cardiovascular events increased as the eGFR decreased, with a significant
      difference only between CKD stage G5 (eGFR: under 15 ml/min/1.73 m2) and CKD
      stage G3a (eGFR: 45-59 ml/min/1.73 m2) (hazard ratio 3.16, 95% confidence
      interval 1.28 to 7.76). Thus, the risk of CVD and all-cause death was related to
      the decrease in eGFR, but not necessarily elevated in proportion to progression
      of the CKD stage in Japanese patients with predialysis CKD under a nephrologist's
      care.

PMID- 27884401
TI  - The "Make Love, Not War" Ape: Bonobos and Late Twentieth-Century Explanations for
      War and Peace.
AB  - Why do people fight wars? Following the devastation of the Second World War, this
      question became particularly pressing. Postwar scholars in the human sciences,
      from political science to anthropology, investigated the role of human nature in
      the causes of war even as they debated the very meaning of human nature itself.
      Among the wide-ranging efforts of postwar social and behavioral scientists to
      explain the causes of war, research on primate aggression became a compelling
      approach to studying the evolution of human warfare. In contrast, primatologist
      Frans de Waal's popular and scientific publications on primate reconciliation
      emphasized the naturalness of conflict resolution and peacemaking, thereby
      providing a counterpoint to the pessimism of aggression research while
      simultaneously shoring up the logic of simian analogy. De Waal's popular books
      heralded the "make love, not war" bonobo as humans' evolutionary next-of-kin and
      contributed to raising public interest in bonobos during the late twentieth
      century, although the apes' popular reputation subsequently exceeded the
      scientific discourse about them.

PMID- 27884398
TI  - Slow-paced respiration therapy to treat symptoms in pulmonary arterial
      hypertension.
AB  - OBJECTIVE: To determine the feasibility of using slow-paced respiration therapy
      to treat symptoms in women with pulmonary arterial hypertension (PAH).
      BACKGROUND: People with PAH report increased dyspnea, fatigue and sleep
      disturbance that can impair health-related quality of life (HRQOL). METHODS: Ten
      women with PAH received 8-weeks of daily, 15 min sessions using slow-paced
      respiration therapy via the RESPeRATETM device. Participants had baseline and
      follow up assessments including plasma norepinephrine and interleukin-6 (IL-6),
      self-report questionnaires to measure dyspnea, fatigue, depressive symptoms,
      sleep and HRQOL along with 7-day actigraphy and sleep diaries. RESULTS: The mean
      age was 50 years. Adherence to the intervention was 92%. There was decrease in
      median IL-6 levels [1.3 +/- 0.5 to 1.1 +/- 0.4, 95% CI (0.03-0.43)] over the
      study period. Sleep disturbance decreased, depressive symptoms decreased and
      HRQOL scores decreased (higher scores indicate worse HRQOL). CONCLUSIONS: In this
      pilot study, slow-paced respiration therapy is feasible in patients with PAH and
      may improve symptoms and lower IL-6.

PMID- 27884402
TI  - Process and Impact of Niels Bohr's Visit to Japan and China in 1937: A
      Comparative Perspective.
AB  - At the beginning of the twentieth century, Japan and China, each for its own
      reasons, invited the famous physicist Niels Bohr to visit and give lectures. Bohr
      accepted their invitations and made the trip in 1937; however, the topics of his
      lectures in the two countries differed. In Japan, he mainly discussed quantum
      mechanics and philosophy, whereas in China, he focused more on atomic physics.
      This paper begins with a detailed review of Bohr's trip to Japan and China in
      1937, followed by a discussion of the impact of each trip from the perspective of
      the social context. We conclude that the actual effect of Bohr's visit to China
      and Japan involved not only the spreading of Bohr's knowledge but also clearly
      hinged on the current status and social background of the recipients. Moreover,
      the impact of Bohr's trip to East Asia demonstrates that, as is the case for
      scientific exchanges at the international level, the international exchange of
      knowledge at the individual level is also powerful, and such individual exchange
      can even promote exchange on the international level.

PMID- 27884403
TI  - Chairside CAD/CAM materials. Part 2: Flexural strength testing.
AB  - OBJECTIVE: Strength is one of the preferred parameters used in dentistry for
      determining clinical indication of dental restoratives. However, small dimensions
      of CAD/CAM blocks limit reliable measurements with standardized uniaxial bending
      tests. The objective of this study was to introduce the ball-on-three-ball (B3B)
      biaxial strength test for dental for small CAD/CAM block in the context of the
      size effect on strength predicted by the Weibull theory. METHODS: Eight
      representative chairside CAD/CAM materials ranging from polycrystalline zirconia
      (e.max ZirCAD, Ivoclar-Vivadent), reinforced glasses (Vitablocs Mark II, VITA;
      Empress CAD, Ivoclar-Vivadent) and glass-ceramics (e.max CAD, Ivoclar-Vivadent;
      Suprinity, VITA; Celtra Duo, Dentsply) to hybrid materials (Enamic, VITA; Lava
      Ultimate, 3M ESPE) have been selected. Specimens were prepared with highly
      polished surfaces in rectangular plate (12*12*1.2mm3) or round disc (O=12mm,
      thickness=1.2mm) geometries. Specimens were tested using the B3B assembly and the
      biaxial strength was determined using calculations derived from finite element
      analyses of the respective stress fields. Size effects on strength were
      determined based on results from 4-point-bending specimens. RESULTS: A good
      agreement was found between the biaxial strength results for the different
      geometries (plates vs. discs) using the B3B test. Strength values ranged from
      110.9MPa (Vitablocs Mark II) to 1303.21MPa (e.max ZirCAD). The strength
      dependency on specimen size was demonstrated through the calculated effective
      volume/surface. SIGNIFICANCE: The B3B test has shown to be a reliable and simple
      method for determining the biaxial strength restorative materials supplied as
      small CAD/CAM blocks. A flexible solution was made available for the B3B test in
      the rectangular plate geometry.

PMID- 27884404
TI  - Exposure to perfluoroalkyl substances and thyroid function in pregnant women and
      children: A systematic review of epidemiologic studies.
AB  - INTRODUCTION: Thyroid hormones (THs) are especially important for brain
      maturation and development during the fetal period and childhood. Several
      epidemiological studies have assessed the possible association between exposure
      to perfluoroalkyl substances (PFAS) and thyroid outcomes during the early stages
      of life. We aimed to review this evidence. METHODS: We conducted a systematic
      review in compliance with the PRISMA Statement (search conducted in PubMed and
      Embase, as well as in the citations of the selected articles). We chose studies
      if they dealt with thyroid-stimulating hormone (TSH), triiodothyronine (T3),
      thyroxin (T4), or thyroid dysfunctions, and perfluorohexane sulfonate (PFHxS),
      perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) or
      perfluorononanoic acid (PFNA) measured in the blood of pregnant women and/or
      children up to 19years old. RESULTS: We included in this review three cross
      sectional, one case-control, and six cohort studies (publication: 2011-2015),
      focusing on prenatal life (n=7), childhood (n=2) or both periods (n=1). We
      observed a high degree of heterogeneity across studies in terms of sampling time
      (different gestational weeks, at birth, or childhood), outcomes, adjustment for
      potential confounders, and statistical approach. We found some evidence of a
      positive association between PFHxS and PFOS exposure and TSH levels measured in
      maternal blood, and PFNA and TSH levels measured in the blood of boys aged
      >=11years. CONCLUSION: Although there is a small number of studies with
      comparable data, we found some consistency of a positive association between
      maternal or teenage male exposure to some PFAS and TSH levels based on the
      current literature. However, further studies are required to confirm these
      possible relationships.

PMID- 27884405
TI  - Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice.
AB  - Zika virus (ZIKV) persists in the semen of male patients, a first for flavivirus
      infection. Here, we demonstrate that ZIKV can induce inflammation in the testis
      and epididymidis, but not in the prostate or seminal vesicle, and can lead to
      damaged testes after 60 days post-infection in mice. ZIKV induces innate immune
      responses in Leydig, Sertoli, and epididymal epithelial cells, resulting in the
      production of pro-inflammatory cytokines/chemokines. However, ZIKV does not
      induce a rapid and abundant cytokine production in peritubular cell and
      spermatogonia, suggesting that these cells are vulnerable for ZIKV infection and
      could be the potential repositories for ZIKV. Our study demonstrates a
      correlation between ZIKV and testis infection/damage and suggests that ZIKV
      infection, under certain circumstances, can eventually lead to male infertility.

PMID- 27884406
TI  - [Clinical approach to imported eosinophilia].
AB  - Eosinophilia is a common finding in international travelers and immigrants, being
      an helmintic infection its main etiology. The positive predictive value of
      eosinophilia for an helmintosis is low in travellers. Eosinophilia may be an
      incidental finding, or symptomatic, and it represents a clinical challenge due to
      the low sensitivity and specificity of direct and indirect parasitological
      diagnostic tests, respectively. It requires a structured approach based on
      geographical areas, environmental exposures and behavioral risks, and associated
      symptoms. The initial assessment should include a comprehensive and tailored
      anamnesis and physical examination, basic laboratory tests, a complete
      parasitological examination of stool samples and a Strongyloides stercoralis
      serology, supplemented with other explorations guided by epidemiological and
      clinical suspicion. Empiric treatment with albendazole and/or ivermectin (plus
      praziquantel if risk of schistosomiasis) is an option for unidentified persistent
      eosinophilia after study, and in persons in whom a proper assessment or follow-up
      can not be assured. In patients at risk for estrongiloidosis who are candidates
      for immunosuppressive therapies, it is indicated a prior screening and treatment
      to prevent a future hyperinfestation syndrome.

PMID- 27884407
TI  - Activity of Artemisia annua infusions on epimastigotes of Trypanosoma cruzi.

PMID- 27884408
TI  - Albumin may significantly increase mortality in burn patients: Re-analysis of a
      systematic review.

PMID- 27884409
TI  - Percutaneous Perventricular Device Closure of Ventricular Septal Defect: From
      Incision to Pinhole.
AB  - BACKGROUND: As an alternative to open surgical repair, perventricular device
      closure provides minimally invasive treatment for doubly committed subarterial
      ventricular septal defects. However, unlike percutaneous transcatheter access,
      mini-thoracotomy is still needed. This report describes the percutaneous
      perventricular device closure technique and its short-term results for this type
      of heart defect. METHODS: Sixteen patients who had isolated doubly committed
      subarterial ventricular septal defects underwent percutaneous perventricular
      device closure. By puncture of the chest wall and subsequently the infundibulum
      of the right ventricle under continuous guidance of transesophageal
      echocardiography, the guidewire and the delivery sheath were advanced into the
      heart to complete the perventricular closure. Closure outcomes and possible
      complications were measured in the hospital and during 1-year follow-up. RESULTS:
      Closure was successful in 15 patients (93.8%). No deaths, residual shunting, new
      valve regurgitation, or arrhythmias occurred either perioperatively or during the
      entire follow-up period. One patient had pericardial effusion and tamponade, and
      the procedure was converted to mini-thoracotomy perventricular closure. The mean
      hospital stay was 3.5 +/- 2.0 days (range, 3.0 to 6.0 days), and only 1 patient
      required a blood transfusion (6.3%). CONCLUSIONS: Percutaneous perventricular
      device closure of isolated doubly committed subarterial ventricular septal
      defects appeared to be safe and efficacious, with acceptable short-term outcomes.
      Larger studies and long-term follow-up are needed for further evaluation.

PMID- 27884410
TI  - Complications After Cardiac Operations: All Are Not Created Equal.
AB  - BACKGROUND: Postoperative complications are associated with increased morbidity
      and mortality after cardiac operations. We sought to quantify the effect of
      multiple complications on noninstitutionalized recovery after cardiac operations.
      METHODS: We identified 2,477 adult patients from our institutional cardiac
      surgery database who underwent one of seven index cardiac surgical operations
      from 2011 to 2014. We calculated failure-to-rescue rates for all individual
      complications and combinations of complications. We used multivariable logistic
      regression to determine the effect of the interaction of postoperative
      complications on our primary outcome of operative death and secondary outcomes of
      prolonged hospital length of stay and discharge to a location other than home.
      RESULTS: From 2011 to 2014, at least one complication occurred in 366 patients
      (14.8%), and multiple complications occurred in 102 (4.1%), including three
      complications in 20 (0.8%). Operative mortality occurred in 41% of patients with
      multiple complications vs in 4.9% of those with an isolated complication and in
      0.7% of those without complications. Significant interactions that negatively
      affected survival were noted between nearly every combination of complications.
      The occurrence of renal failure and unplanned reoperation together were
      associated with increased deaths (odds ratio, 108.4; 95% confidence interval,
      13.5 to 869.9; p < 0.001). Median hospital length of stay and discharge rates to
      a location other than home correlated positively with the number of postoperative
      complications. CONCLUSIONS: Major complications after cardiac operations are
      associated with an increased risk for operative death, longer hospital length of
      stay, and higher rates of discharge to a location other than home. These adverse
      outcomes are magnified when multiple complications are encountered.

PMID- 27884411
TI  - Celsior Versus Microplegia: Analysis of Myocardial Protection in Elective Aortic
      Valve Replacement.
AB  - BACKGROUND: Previous studies have analyzed the efficacy of crystalloid
      cardioplegic solutions, but the use of Celsior (Genzyme Corp, Boston, MA) as a
      crystalloid cardioplegic solution has not been evaluated. METHODS: In this
      observational retrospective study, Celsior crystalloid solution was compared with
      an all-blood continuous myocardial protection (microplegia). The study included
      all patients who underwent elective aortic valve replacement operations in whom
      the myocardial protection was Celsior or microplegia. The primary end points were
      surrogates of myocardial protection and death at 30 days. The secondary end point
      was the safety analysis of the use of Celsior. RESULTS: The study included 631
      patients, divided in two groups: 219 (34.7%) with microplegia and 412 (65.3%)
      with Celsior. Troponin T release accurately predicted postoperative death (area
      under the receiver operating characteristic curve = 0.85). Troponin T increased
      with the duration of clamp time, and the adjusted time-related increase was lower
      in the Celsior group. There were no statistically significant differences in the
      postoperative use of inotropic medication or intraaortic balloon pump. Adjusted
      postoperative death was lower in Celsior group (odds ratio, 0.33; 95% confidence
      interval, 0.15 to 0.76). There were no allergic reactions attributed to Celsior
      and no unexpected toxicity with the use of Celsior (coagulopathy, renal
      dysfunction, liver dysfunction, or encephalopathy). CONCLUSIONS: Isolated
      crystalloid Celsior may be an optimal and safe myocardial protection strategy in
      aortic valve replacement operations.

PMID- 27884412
TI  - The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2017 Update on
      Outcomes and Quality.
AB  - Established in 1989, The Society of Thoracic Surgeons Adult Cardiac Surgery
      Database is one of the most comprehensive clinical data registries in health
      care. It is widely regarded as the gold standard for benchmarking risk-adjusted
      outcomes in cardiac surgery and is the foundation for all quality measurement and
      improvement activities of The Society of Thoracic Surgeons. This is the second in
      a series of annual reports that summarizes current aggregate national outcomes in
      cardiac surgery and reviews database-related activities in the areas of quality
      measurement and performance improvement during the past year.

PMID- 27884413
TI  - Peroxisome proliferator-activated receptor gamma down-regulation mediates the
      inhibitory effect of d-delta-tocotrienol on the differentiation of murine 3T3
      F442A preadipocytes.
AB  - Tocotrienols accelerate the degradation of 3-hydroxy-3-methylglutaryl coenzyme A
      (HMG CoA) reductase that catalyzes the biosynthesis of mevalonate; the latter is
      essential for preadipocyte differentiation. Tocotrienols also down-regulate
      peroxisome proliferator-activated receptor gamma (PPARgamma), a key regulator of
      adipocyte differentiation. We hypothesized that mevalonate deprivation and
      PPARgamma down-regulation mediate d-delta-tocotrienol-induced inhibition of
      adipocyte differentiation. The objectives of this study were to determine the
      effect of d-delta-tocotrienol on 3T3-F442A preadipocyte differentiation and the
      involvement of PPARgamma and mevalonate. Murine 3T3-F442A preadipocytes were
      incubated with d-delta-tocotrienol (2.5-10 MUmol/L) for 8 days. AdipoRed assay
      and Oil Red O staining showed that d-delta-tocotrienol dose-dependently reduced
      the intracellular triglyceride content. Concomitantly, d-delta-tocotrienol dose
      dependently inhibited glucose uptake by 3T3-F442A cells and the expression of
      GLUT4, HMG CoA reductase, and p-Akt proteins. The effects of d-delta-tocotrienol
      on intracellular triglyceride content and glucose uptake were attenuated by
      rosiglitazone, an agonist of PPARgamma, but not supplemental mevalonate (100
      MUmol/L). In contrast, mevalonate, but not rosiglitazone, reversed the effects of
      lovastatin, a competitive inhibitor of HMG CoA reductase shown to inhibit
      adipocyte differentiation via mevalonate deprivation. Trypan blue staining
      revealed no changes in cell viability after a 48-hour incubation of 3T3-F442A
      cells with d-delta-tocotrienol (0-80 MUmol/L), suggesting that the adipogenesis
      suppressive activity of d-delta-tocotrienol was independent of cytotoxicity. In
      conclusion, these findings demonstrate the antiadipogenic effect of d-delta
      tocotrienol via PPARgamma down-regulation.

PMID- 27884414
TI  - Low muscle mass is associated with metabolic syndrome in Korean adolescents: the
      Korea National Health and Nutrition Examination Survey 2009-2011.
AB  - Little is known about the relationship between low muscle mass (LMM) and
      metabolic risk factors in adolescents. We hypothesized that LMM in adolescents is
      associated with metabolic syndrome (MetS) and its components in Korean
      adolescents. This cross-sectional study included 1420 participants (749 males and
      671 females), aged 12 to 19 years, who participated in the 2009-2011 Korea
      National Health and Nutrition Examination Surveys. Appendicular skeletal muscle
      mass was divided by body weight, and any value below the lower quintile of the
      study population, according to each age and sex category, was considered to
      represent LMM. A participant was considered to have MetS if he/she demonstrated
      at least 3 of the National Cholesterol Education Program-Adult Treatment Panel
      III criteria. The overall prevalence of MetS was 4.9%, with a prevalence of 7.1%
      in males and 2.3% in females. Low muscle mass significantly increased the risk of
      MetS, after adjusting for potential covariates (odds ratio [OR], 5.28; 95%
      confidence interval, 2.76-10.13). Similarly, the ORs for the MetS components were
      significantly higher in individuals with LMM than in those without LMM. In the
      subgroup analysis, LMM was significantly associated with MetS in both adolescent
      boys and girls. In addition, the adjusted OR was significantly higher in
      individuals with LMM than in those without, after stratifying the groups by age.
      In conclusion, our results suggest that adolescents with LMM may have a high risk
      of MetS. Public health initiatives are needed to develop interventions for
      preventing and treating LMM in adolescents.

PMID- 27884415
TI  - Uniformly active phase loaded selective catalytic reduction catalysts (V2O5/TNTs)
      with superior alkaline resistance performance.
AB  - In this work, protonated titanate nanotubes was performed as a potential useful
      support and different vanadium precursors (NH4VO3 and VOSO4) were used to
      synthesize deNOx catalysts. The results showed that VOSO4 exhibited better
      synergistic effect with titanate nanotubes than NH4VO3, which was caused by the
      ion-exchange reaction. Then high loading content of vanadium, uniformly active
      phase distribution, better dispersion of vanadium, more acid sites, better
      V5+/V4+ redox cycles and superior oxygen mobility were achieved. Besides, VOSO4
      based titanate nanotubes catalysts also showed enhanced alkaline resistance than
      particles (P25) based catalysts. It was strongly associated with its abundant
      acid sites, large surface area, flexible redox cycles and oxygen transfer
      ability. For the loading on protonated titanate nanotubes, active metal with
      cation groups was better precursors than anion ones. V2O5/TNTs catalyst was a
      promising substitute for the commercial vanadium catalysts and the work conducted
      herein provided a useful idea to design uniformly active phase loaded catalyst.

PMID- 27884417
TI  - Nerve Decompression Surgery After Total Hip Arthroplasty: What Are the Outcomes?
AB  - BACKGROUND: The purpose of our study was to compare (1) muscle strength; (2)
      pain; (3) sensation; (4) various outcome measurement scales between post-total
      hip arthroplasty (THA) patients who had a sciatic nerve injury and did or did not
      receive decompression surgery for this condition; and (5) to compare these
      findings with current literature. METHODS: Nineteen patients who had nerve injury
      after THA were reviewed. Patients were stratified into those who had a nerve
      decompression (n = 12), and those who had not (n = 7). Motor strength was
      evaluated using the Muscle Strength Testing Scale. Pain was evaluated by using
      the visual analogue scale. Systematic literature search was performed to compare
      the findings of this study with others currently published. RESULTS: The
      decompression group had a significant improvement in motor strength and the
      visual analog scale scores as compared with nonoperative group. Patients in
      decompression group had a significant larger increase in the mean Harris hip
      score and University of California Los Angeles score. There was no significant
      difference in the increase of Short Form-36 physical and mental scores between
      the 2 groups. Literature review for nonoperative management yielded 5 studies (93
      patients), with 33% improvement. There were 7 studies (81 patients) on nerve
      decompression surgery, with 75% improvement. CONCLUSION: This study demonstrates
      the benefits of nerve decompression surgery in patients who had sciatic nerve
      injury after THA, as evidenced by results of standardized outcome measurement
      scales. It is possible to achieve improvements in terms of strength, pain, and
      clinical outcomes. Comparative studies with larger cohorts are needed to fully
      assess the best candidates for this procedure.

PMID- 27884416
TI  - Hemin ameliorates influenza pneumonia by attenuating lung injury and regulating
      the immune response.
AB  - The anti-influenza activity of hemin, an inducer, activator and the substrate of
      heme oxygenase-1 (HO-1), was examined both in vitro and in vivo. The human lung
      carcinoma cell line A549 was used to evaluate the in vitro effect of hemin on
      influenza A virus (IAV) replication. A mouse model was used to examine the in
      vivo activity of hemin. Observation indexes included survival rate and body
      weight of mice, virus load and pathological examination of the lungs, and
      characterization of the systemic and local immune responses. The results showed
      that hemin could induce HO-1 expression in A549 cells and inhibit IAV replication
      in vitro. The in vivo results showed that injection of hemin could protect mice
      from death and body weight loss caused by IAV infection. Hemin was administered
      both at initial and progressive stages of influenza pneumonia (1 day and 4 days
      after virus infection, respectively) and showed significant anti-influenza
      activity under both conditions. However, the results showed that although hemin
      could induce HO-1 expression in vivo, it could not inhibit IAV replication in
      vivo. Pathological examination showed that hemin significantly attenuated lung
      tissue injury caused by IAV. Further study showed that hemin could regulate the
      immune response to IAV infection by reducing lymphocytopenia and local
      inflammatory cytokine increases caused by IAV infection. This study shows that
      hemin has the potential for the treatment of IAV infection and its effect may be
      due to attenuation of lung injury and regulation of the immune response.

PMID- 27884419
TI  - A Novel Deep Inspiration Maneuver for Difficult Transseptal Puncture.
AB  - Transseptal puncture (TSP) may not be possible in cases of an elastic,
      aneurysmal, or thickened interatrial septum (IAS). During deep inspiration (DI),
      the chest wall expands and the diaphragm descends. This makes intrapleural
      pressure to become more negative, which leads to movement of the IAS to the right
      side. The aim of this study was to verify prospectively the feasibility, safety,
      and outcome of DI associated with conventional TSP technique in patients with
      challenging IAS anatomy. From September 2012 to May 2016, 224 patients underwent
      TSP due to different indications. Patients were divided into 2 groups: 213
      patients in whom the left atrium was successfully accessed in 3 attempts were
      grouped as conventional TSP group and 11 patients in whom left atrium access was
      failed after 3 conventional attempts were grouped as DI-TSP group. Conventional
      TSP was successful in 89.6% of patients with the first attempt. Second and third
      attempts were required in 4.1% and 1.4%, respectively. Septal puncture was
      achieved at the first attempt in 10 patients within a median of 1 second of DI
      maneuver (interquartile range, 1 to 3) and without any complications. Challenging
      IAS anatomy consisting of IAS aneurysm, a thick IAS, and an excessively mobile
      IAS were more frequent in the DI-TSP group (45% to 8%, 27% to 3%, and 21% to 5%,
      respectively, p <0.001). In conclusion, TSP by using the DI maneuver may be a
      reliable and safe method after failed conventional attempts. If there is any
      doubt about the correct location of the needle, additional imaging modalities
      have to be used.

PMID- 27884418
TI  - Heterotopic Ossification Prophylaxis After Total Hip Arthroplasty: Randomized
      Trial of 400 vs 700 cGy.
AB  - BACKGROUND: Heterotopic ossification (HO) is a known complication following total
      hip arthroplasty. Radiation is an effective prophylaxis, but an optimal protocol
      has yet to be determined. We performed a randomized, double-blinded clinical
      trial in high-risk patients to determine the efficacy of 400 vs 700 cGy doses of
      radiation. METHODS: One hundred forty-seven patients undergoing total hip
      arthroplasty and at high risk for HO at an urban medical center were randomized
      to receive either a single 400 or 700 cGy dose of radiation postoperatively. High
      risk was defined as a diagnosis of diffuse idiopathic skeletal hyperostosis,
      hypertrophic osteoarthritis, ankylosing spondylitis, or history of previous HO.
      Radiation was administered on the first or second postoperative day. A single
      blinded reviewer graded radiographs taken immediately postoperatively and at a
      minimum of 6 months postoperatively using the Brooker classification. Progression
      was defined as an increase in Brooker classification. Operative data including
      surgical approach, implant fixation, revision surgery, and postoperative range of
      motion data were also collected. RESULTS: A significantly greater portion of
      patients who received the 400 cGy dose demonstrated progression of HO than
      patients who received the 700 cGy dose. There were no wound complications. No
      preoperative factors were associated with a higher rate of progression. Patients
      who progressed had less flexion on physical examination than patients who did not
      progress, but this was not clinically significant. CONCLUSION: Seven hundred
      centigray was superior to 400 cGy in preventing HO formation following total hip
      arthroplasty in high-risk patients and may be the more effective treatment in
      this population. Further studies comparing 700 cGy to dosages between 400 and 700
      cGy may help to clarify if a more optimal dose can be identified.

PMID- 27884420
TI  - Referral for Specialist Follow-up and Its Association With Post-discharge
      Mortality Among Patients With Systolic Heart Failure (from the National Heart
      Failure Audit for England and Wales).
AB  - For patients admitted with worsening heart failure (HF), early follow-up after
      discharge is recommended. Whether outcomes can be improved when follow-up is done
      by cardiologists is uncertain. We aimed to determine the association between
      cardiology follow-up and risk of death for patients with HF discharged from
      hospital. Using data from the National Heart Failure Audit (England and Wales),
      we investigated the effect of referral to cardiology follow-up on 30-day and 1
      year mortality in 68,772 patients with HF and a reduced left ventricular ejection
      fraction discharged from 185 hospitals from 2007 to 2013. The primary analyses
      used instrumental variable analysis complemented by hierarchical logistic and
      propensity-matched models. At the hospital level, rates of referral to
      cardiologists varied from 6% to 96%. The median odds ratio (OR) for referral to
      cardiologist was 2.3 (95% confidence interval [CI] 2.1 to 2.5), suggesting that,
      on average, the odds of a patient being referred for cardiologist follow-up after
      discharge differed ~2.3 times from one randomly selected hospital to another one.
      Based on the proportion of patients (per region) referred for cardiology follow
      up, referral for cardiology follow-up was associated with lower 30-day (OR 0.70;
      95% CI 0.55 to 0.89) and 1-year mortality (OR 0.81; 95% CI 0.68 to 0.95) compared
      with no plans for cardiology follow-up (i.e., standard follow-up done by family
      doctors). Results from hierarchical logistic models and propensity-matched models
      were consistent (30-day mortality OR 0.66; 95% CI 0.61 to 0.72 and 0.66; 95% CI
      0.58 to 0.76 for hierarchical and propensity matched models, respectively). For
      patients with HF and a reduced left ventricular ejection fraction admitted to
      hospital with worsening symptoms, referral to cardiology services for follow-up
      after discharge is strongly associated with reduced mortality, both early and
      late.

PMID- 27884421
TI  - Interpreting the Incremental Cardiopulmonary Exercise Test.
AB  - The incremental cardiopulmonary exercise test (CPET) is an increasingly used
      diagnostic method that serves to evaluate patients with chief complaint of
      dyspnea during exercise. Performing maximal symptom-limited CPET can show if the
      tested subject has a reduced exercise capacity and give clues to the mechanism of
      such exercise capacity reduction, cardiac, pulmonary, or pulmonary vascular
      source. In this review, it is suggested that the evaluation of the complex
      results of CPET should be performed by first determining if
      myocardial/circulatory insufficiency is present and second if there is gas
      exchange abnormality. By looking with scrutiny at the oxygen consumption (VO2)
      versus work rate plot, one can see if oxygen delivery is adequate or if it is
      hampered by abnormally reduced blood flow through skeletal muscle. Elevated
      ventilatory equivalent of carbon dioxide at the ventilatory threshold and or
      arterial oxygen desaturation during effort, strongly suggest gas exchange
      abnormalities. The absence of circulatory insufficiency and gas exchange
      abnormalities, almost always suggest normal response to effort or deconditioning
      whenever peak VO2 is below the maximal predicted value.

PMID- 27884422
TI  - A New Risk Score to Predict Long-Term Cardiac Mortality in Patients With Acute
      Myocardial Infarction Complicated by Cardiogenic Shock and Treated With Primary
      Percutaneous Intervention.
AB  - Poor data exist about predictors of long-term cardiac mortality in patients
      presenting acute myocardial infarction (AMI) complicated by cardiogenic shock
      (CS) treated with primary percutaneous coronary intervention (p-PCI), and current
      risk-adjustment models in this setting are not adequate. We retrospectively
      analyzed our registry of patients with AMI treated with p-PCI. The aim of this
      study was to identify the independent predictors of 2-year cardiac mortality in
      patients presenting CS. A Risk Score was created assigning at any independent
      variable a value directly correlated with its power to increase mortality. From
      1995 to 2013, 4,078 consecutive patients underwent primary PCI for AMI. Of these,
      388 patients (10.5%) had CS on admission. The p-PCI procedural success was 85%.
      At 2-year follow-up, the overall cardiac mortality rate was 48%. The independent
      predictors related with mortality were: out of hospital cardiac arrest (OHCA)
      (hazard ratio [HR] 1.51; p = 0.04), age >75 years (HR 2.09; p <=0.001), and
      failure p-PCI (HR 2.30; p <0.001). On the basis of the HR obtained, we assigned
      an incremental value to each independent variable identified (OHCA: 0.5 points,
      age>75 years: 1 point, failed p-PCI: 1.5 points). The mortality rates among
      different score risk level were highly significant (p <0.001): 32% score risk 1
      (points 0), 58% score risk 2 (points 0.5-2), and 83% score risk 3 (points >2),
      respectively. In conclusion, OHCA, age >75 years, and failed p-PCI are strong
      predictors of 2-year cardiac mortality. On the basis of this, a rapid score tool
      could be useful to identify patients at major risk of death.

PMID- 27884424
TI  - Vision as a Beachhead.
AB  - When neural circuits develop abnormally due to different genetic deficits and/or
      environmental insults, neural computations and the behaviors that rely on them
      are altered. Computational theories that relate neural circuits with specific
      quantifiable behavioral and physiological phenomena, therefore, serve as
      extremely useful tools for elucidating the neuropathological mechanisms that
      underlie different disorders. The visual system is particularly well suited for
      characterizing differences in neural computations; computational theories of
      vision are well established, and empirical protocols for measuring the parameters
      of those theories are well developed. In this article, we examine how
      psychophysical and neuroimaging measurements from human subjects are being used
      to test hypotheses about abnormal neural computations in autism, with an emphasis
      on hypotheses regarding potential excitation/inhibition imbalances. We discuss
      the complexity of relating specific computational abnormalities to particular
      underlying mechanisms given the diversity of neural circuits that can generate
      the same computation, and we discuss areas of research in which computational
      theories need to be further developed to provide useful frameworks for
      interpreting existing results. A final emphasis is placed on the need to extend
      existing ideas into developmental frameworks that take into account the dramatic
      developmental changes in neurophysiology (e.g., changes in excitation/inhibition
      balance) that take place during the first years of life, when autism initially
      emerges.

PMID- 27884423
TI  - Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in
      Schizophrenia.
AB  - BACKGROUND: The axons of chandelier cells (ChCs) target the axon initial segment
      of pyramidal neurons, forming an array of boutons termed a cartridge. In
      schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid
      (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of
      axon initial segments detectable by immunoreactivity for the alpha2 subunit of
      the GABAA receptor is higher in layers 2/superficial 3 of the prefrontal cortex.
      These findings were interpreted as compensatory responses to lower GABA levels in
      ChCs. However, we recently found that in schizophrenia, ChC cartridge boutons
      contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase
      (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To
      understand these findings we quantified the densities of ChC cartridges
      immunoreactive for vesicular GABA transporter (vGAT+), which is present in all
      cartridge boutons, and the subset of cartridges that contain calbindin (CB+).
      METHODS: Prefrontal cortex tissue sections from 20 matched pairs of schizophrenia
      and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB.
      RESULTS: The mean density of vGAT+/CB+ cartridges was 2.7-fold higher,
      exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB
      cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67
      protein levels per ChC bouton nor the number of boutons per cartridge differed
      between subject groups. CONCLUSIONS: Our findings of a greater density of CB+ ChC
      cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that
      the normal developmental pruning of these cartridges is blunted in the illness.

PMID- 27884425
TI  - The Eating-Disorder Associated HDAC4A778T Mutation Alters Feeding Behaviors in
      Female Mice.
AB  - BACKGROUND: While eating disorders (EDs) are thought to result from a combination
      of environmental and psychological stressors superimposed on genetic
      vulnerability, the neurobiological basis of EDs remains incompletely understood.
      We recently reported that a rare missense mutation in the gene for the
      transcriptional repressor histone deacetylase 4 (HDAC4) is associated with the
      risk of developing an ED in humans. METHODS: To understand the biological
      consequences of this missense mutation, we created transgenic mice carrying this
      mutation by introducing the alanine to threonine mutation at position 778 of
      mouse Hdac4 (corresponding to position 786 of the human protein). Bioinformatic
      analysis to identify Hdac4-regulated genes was performed using available
      databases. RESULTS: Male mice heterozygous for HDAC4A778T did not show any
      metabolic or behavioral differences. In contrast, female mice heterozygous for
      HDAC4A778T display several ED-related feeding and behavioral deficits depending
      on housing condition. Individually housed HDAC4A778T female mice exhibit reduced
      effortful responding for high-fat diet and compulsive grooming, whereas group
      housed female mice display increased weight gain on high-fat diet, reduced
      behavioral despair, and increased anxiety-like behaviors. Bioinformatic analysis
      identifies mitochondrial biogenesis including synthesis of glutamate/gamma
      aminobutyric acid as a potential transcriptional target of HDAC4A778T activity
      relevant to the behavioral deficits identified in this new mouse model of
      disordered eating. CONCLUSIONS: The HDAC4A778T mouse line is a novel model of ED
      related behaviors and identifies mitochondrial biogenesis as a potential
      molecular pathway contributing to behavioral deficits.

PMID- 27884427
TI  - Sample injection strategy to increase throughput in counter-current
      chromatography: Case study of Honokiol purification.
AB  - Counter-current chromatography (CCC) has been widely used as a preparative
      separation method to purify natural products from plant extracts and fermentation
      broths. Traditionally, throughput optimization in CCC has focused on sample
      concentration and sample volume. In this paper sample injection was considered as
      consisting of three variables: injection flow rate, post-injection flow rate and
      sample solvent. The effects of these parameters were studied using a honokiol
      purification from a Magnolia officinalis bark extract as a case study aiming to
      achieve the highest throughput/yield ratio for greater than 99% purity of this
      potential anti-cancer drug obtained for submission to the Chinese FDA. An
      injection method was established that increased the throughput of honokiol by
      46.5% (from 3.05g/h to 4.47g/h), and decreased the solvent consumption of mobile
      phase and stationary phase per gram of honokiol by 40.0% (from 0.68L/g to
      0.41L/g) and 48.4% (from 0.40L/g to 0.21L/g) respectively. These results show the
      importance of understanding the whole injection process when optimizing a given
      CCC separation.

PMID- 27884426
TI  - Preparation and application of immobilized enzymatic reactors for consecutive
      digestion with two enzymes.
AB  - The bottom up strategy has drawn much attention due to the high accuracy,
      reliability, and reproducibility in protein identification in which proteins are
      digested into peptides. However, conventional solution-based digestion and
      enzymatic reactor with one protease immobilized cannot satisfy high throughput
      proteolysis of complex samples. Application of consecutive hydrolysis by
      enzymatic reactor can be a new strategy for high throughput proteolysis of
      complex samples by adjusting immobilization amount of the enzymes, enzyme ratio,
      as well as hydrolysis order of two enzymes. In this work, we propose immobilized
      enzymatic reactor for consecutive digestion with two enzymes by combining two
      enzyme reactors with trypsin and chymotrypsin immobilized, respectively. Each
      reactor was prepared individually by immobilizing only one protease (trypsin or
      chymotrypsin) to hybrid monolith with SBA-15 particles embedded. Proteolysis
      conditions including hydrolysis order and trypsin to chymotrypsin ratio etc. were
      studied using standard proteins. Best digestion performance was obtained when the
      proteins were digested by trypsin first with trypsin to chymotrypsin ratio of
      1:1. When applying them to digestion of rat liver proteins, total 1651 proteins
      and 11011 peptides were identified by combining four enzymolysis strategies with
      two enzymes including proteolytic digestion in two consecutive enzymatic
      reactors, synergy enzymolysis with two enzymes in one immobilized enzymatic
      reactor and consecutive hydrolysis with two enzymes in-solution digestion
      respectively, in which consecutive enzymolysis in enzymatic reactors gave the
      best results with 1091 proteins and 5071 peptides identified. The reactors showed
      good digestion capability for proteins with different hydrophobicity and
      molecular weights, and will play an important role in high efficient and high
      throughput proteomics research.

PMID- 27884428
TI  - Headspace gas chromatography based methodology for the analysis of aromatic
      substituted quaternary ammonium salts.
AB  - The analysis of quaternary ammonium salts (QAS) using GC is often performed by
      "in injector" pyrolysis to create volatile degradation products for
      quantification purposes. Besides the risk of severe system contamination, the
      application of this approach on aqueous samples is problematic. In this work, the
      sample is treated in a vial with 2,2-dimethoxypropane (DMP) under acidic
      catalysis. In addition to the removal of water and sample enrichment, the QAS are
      decomposed. As HS transfers only volatile compounds to the GC system,
      contamination is avoided. It was found that depending on the presence of benzyl,
      phenyl or methyl groups on the quaternary nitrogen; benzyl chloride, N,N
      dimethylaniline or chloromethane are formed respectively in the sealed vial. All
      these can be used as an analytical target. A calibration curve for benzyl
      chloride could be derived from the pure compound. Chloromethane was generated
      from pure benzyldimethyldecylammonium chloride (BEDIDE), a pure QAS with benzyl
      and methyl groups, to construct a secondary calibration curve using a back
      analysis approach. It has been proven that by quantifying the formed analytical
      targets, the mass balance for the QAS under investigation was close to 100%. The
      presented procedure allows the quantification of any aromatic substituted QAS
      without the need for a matching reference, which is a major advantage over
      existing CE and LC methods The proposed methodology was validated for mouth
      sprays containing benzethonium chloride (BZTCl) or benzoxonium chloride (BZOCl)
      and for denatonium benzoate (DB) in ethylene glycol (EG) based cooling liquids.
      Results showed that the approach provided excellent linearity (R2>=0.999) and
      limits of detection around 0.01MUg/vial for benzyl chloride. It was found that
      the reaction product of DMP and glycerol which was also present in the mouthspray
      and some cooling liquids, caused chromatographic interference with benzyl
      chloride. Treating those samples in the vial with N,O
      bis(trimethylsilyl)trifluoroacetamide (BSTFA) after the enrichment step removes
      the interference and leaves a possible pathway for the simultaneous determination
      of glycerol in those samples.

PMID- 27884430
TI  - Strengthening of C2C12 mouse myoblasts against compression damage by mild cyclic
      compressive stimulation.
AB  - Deep tissue injury (DTI) is a severe kind of pressure ulcers formed by sustained
      deformation of muscle tissues over bony prominences. As a major clinical issue,
      DTI affects people with physical disabilities, and is obviously related to the
      load-bearing capacity of muscle cells in various in-vivo conditions. It is
      important to provide a preventive approach to help muscle cells from being
      damaged by compressive stress. In this study, we hypothesized that cyclic
      compressive stimulation could strengthen muscle cells against compressive damage
      and enhance the cell plasma membrane resealing capability. Monolayer of myoblasts
      was cultured in the cell culture dish covered by a cylinder 0.5% agarose gel. The
      platen indenter was applied with 20% strain on the agarose gel in the Mach-1
      micromechanical system. The vibration was 1Hz sinusoidal function with amplitude
      0.2% strain based on 20% gel strain. Cyclic compressive stimulation for 2h could
      enhance the compressive stress damage threshold of muscle cells, the muscle cell
      plasma membrane resealing ratio and viability of muscle cell under static loading
      as preventive approach. This approach might help to reduce the risk of DTI in
      clinic.

PMID- 27884429
TI  - Development of separation methods for the chiral resolution of hexahelicenes.
AB  - In this short communication we report optimized procedures for the chiral
      separation of non-charged [6]helicene (1) and cationic derivative 1-butyl-3-(2
      methyl[6]helicenyl)-imidazolium bromide (2) using high-performance liquid
      chromatography (HPLC) and supercritical fluid chromatography (SFC) methods. The
      possibility of using capillary electrophoresis (CE) was also tested. The
      satisfactory results were obtained with SFC, where the highly selective
      resolution of four enantiopure 1 and 2 helicenes was achieved in a single run
      within 5min. The semi-preparative procedure for the isolation of P and M
      enantiomers of compound 2, including circular dichroism data, is reported here
      for the first time. The results could be used in further separations and
      analytical applications targeting carbohelicenes vs. positively charged helicene
      derivatives.

PMID- 27884432
TI  - Editorial Comment.

PMID- 27884431
TI  - Computational assessment of hemodynamics-based diagnostic tools using a database
      of virtual subjects: Application to three case studies.
AB  - Many physiological indexes and algorithms based on pulse wave analysis have been
      suggested in order to better assess cardiovascular function. Because these tools
      are often computed from in-vivo hemodynamic measurements, their validation is
      time-consuming, challenging, and biased by measurement errors. Recently, a new
      methodology has been suggested to assess theoretically these computed tools: a
      database of virtual subjects generated using numerical 1D-0D modeling of arterial
      hemodynamics. The generated set of simulations encloses a wide selection of
      healthy cases that could be encountered in a clinical study. We applied this new
      methodology to three different case studies that demonstrate the potential of our
      new tool, and illustrated each of them with a clinically relevant example: (i) we
      assessed the accuracy of indexes estimating pulse wave velocity; (ii) we
      validated and refined an algorithm that computes central blood pressure; and
      (iii) we investigated theoretical mechanisms behind the augmentation index. Our
      database of virtual subjects is a new tool to assist the clinician: it provides
      insight into the physical mechanisms underlying the correlations observed in
      clinical practice.

PMID- 27884433
TI  - Social cognition in schizophrenia and bipolar disorder: Just quantitative
      differences..?

PMID- 27884434
TI  - Relative risks of cardiovascular disease in people prescribed olanzapine,
      risperidone and quetiapine.
AB  - : Antipsychotics may confer long term benefits and risks, including
      cardiovascular disease (CVD) risk. Several studies using routine clinical data
      have reported associations between antipsychotics and CVD but potential
      confounding factors and unclear classification of drug exposure limits their
      interpretation. METHOD: We used data from The Health Improvement Network, a large
      UK primary care database to determine relative risks of (CVD) comparing similar
      groups of people only prescribed olanzapine versus either risperidone or
      quetiapine. We included participants over 18 between 1995 and 2011. To assess
      confounding factors we created propensity scores for being prescribed each
      antipsychotic. We used propensity score matching and Poisson regression to
      calculate the CVD incidence rate ratios for olanzapine versus the other two
      drugs. RESULTS: We identified 18,319 people who received a single antipsychotic
      during follow-up (n=5090 risperidone, 7797 olanzapine and 4613 quetiapine). In
      unmatched analyses, the CVD incidence rate ratio (IRR) for olanzapine versus
      risperidone was 0.63 (0.51-0.77) but the propensity score matched IRR was 0.78
      (0.61-1.02). In the unmatched olanzapine versus quetiapine analysis the IRR
      adjusted for age and sex for olanzapine was 1.52 (1.16-1.98) but the propensity
      score matched analysis gave an IRR of 1.08 (0.79-1.46). CONCLUSIONS: After
      propensity score matching, we found no statistical differences in CVD incidence
      between olanzapine and either risperidone or quetiapine. Analyses which did not
      account for confounding factors produced very different results. Researchers must
      address confounding factors when designing observational studies to assess
      adverse outcomes of drugs, including antipsychotics.

PMID- 27884435
TI  - Statistical comparison of excystation methods in Cryptosporidium parvum oocysts.
AB  - Excystation of sporozoites of Cryptosporidium parvum from oocysts is essential
      for successful in vitro assays. It has also been traditionally used as a measure
      for oocyst viability and infectivity. Laboratories use various excystation
      protocols so there is a need to clarify which method is the best. In this study,
      six different protocols for in vitro excystation of C. parvum oocysts were
      compared to find the most efficient excystation method (expressed as percentage
      excystation). Tested protocols differed in chemical pre-incubation steps,
      excystation media or time of incubation. There were significant differences in
      percentage of excysted oocysts among groups excysted by different methods. There
      were also significant differences in percentage of excysted oocysts between
      methods using pre-incubation with sodium hypochlorite and those without. The
      other variables examined; the presence of trypsin, kind of excystation medium and
      the incubation time, did not show statistical differences in percentage
      excystation among groups. Pre-incubation steps which included sodium
      hypochlorite, enhancing the permeability of the oocysts were found to increase
      the excystation ratio and methods using this step were the most effective.

PMID- 27884436
TI  - Distribution of Foxp3+ T cells in the liver and hepatic lymph nodes of goats and
      sheep experimentally infected with Fasciola hepatica.
AB  - Foxp3 regulatory T cells (Tregs) are now considered to play a key role in
      modulation of immune responses during parasitic helminth infections.
      Immunomodulation is a key factor in Fasciola hepatica infection; however, the
      distribution and role of Foxp3+ Tregs cells have not been investigated in F.
      hepatica infected ruminants. The aim of this study was to evaluate the presence
      of Foxp3+ Tregs in the liver and hepatic lymph nodes from experimentally infected
      sheep and goats during acute and chronic stages of infection. Three groups of
      goats (n=6) and three groups of sheep (n=6) were used in this study. Goats in
      groups 1-2 and sheep in groups 4-5 were orally infected with metacercarie of
      ovine origin. Groups 1 and 4 were killed during the acute stage of the infection,
      at nine days post infection (dpi); groups 2 and 5 were killed during the chronic
      stage, at 15 and19 weeks post infection respectively (wpi). Groups 3 (goats) and
      6 (sheep) were left as uninfected controls. Fluke burdens and liver damage were
      assessed and the avidin-biotin-complex method was used for the
      immunohistochemical study. At nine dpi in acute hepatic lesions, the number of
      both Foxp3+ and CD3+ T lymphocytes increased significantly in goats and sheep. In
      the chronic stages of infection (15-19wpi), the number of Foxp3+ and CD3+ T
      lymphocytes were also significantly increased with respect to control livers,
      particularly in portal spaces with severely enlarged bile ducts (response to
      adult flukes) while the increase was lower in granulomas, chronic tracts and
      smaller portal spaces (response to tissue damage). Foxp3+ Tregs were increased in
      the cortex of hepatic lymph nodes of sheep (chronic infection) and goats (acute
      and chronic infection). The estimated proportion of T cells which were Foxp3+ was
      significantly increased in the large bile ducts and hepatic lymph node cortex of
      chronically infected goats but not sheep. This first report of the expansion of
      Foxp3+ Tregs in acute and chronic hepatic lesions in ruminants suggests that
      these cells may be involved in both parasite survival and modulation of hepatic
      damage. Future studies should be focused on the investigation of parasite
      molecules and cytokines involved in this process.

PMID- 27884437
TI  - Evaluation by latent class analysis of a magnetic capture based DNA extraction
      followed by real-time qPCR as a new diagnostic method for detection of
      Echinococcus multilocularis in definitive hosts.
AB  - A new method, based on a magnetic capture based DNA extraction followed by qPCR,
      was developed for the detection of the zoonotic parasite Echinococcus
      multilocularis in definitive hosts. Latent class analysis was used to compare
      this new method with the currently used phenol-chloroform DNA extraction followed
      by single tube nested PCR. In total, 60 red foxes and coyotes from three
      different locations were tested with both molecular methods and the sedimentation
      and counting technique (SCT) or intestinal scraping technique (IST). Though based
      on a limited number of samples, it could be established that the magnetic capture
      based DNA extraction followed by qPCR showed similar sensitivity and specificity
      as the currently used phenol-chloroform DNA extraction followed by single tube
      nested PCR. All methods have a high specificity as shown by Bayesian latent class
      analysis. Both molecular assays have higher sensitivities than the combined SCT
      and IST, though the uncertainties in sensitivity estimates were wide for all
      assays tested. The magnetic capture based DNA extraction followed by qPCR has the
      advantage of not requiring hazardous chemicals like the phenol-chloroform DNA
      extraction followed by single tube nested PCR. This supports the replacement of
      the phenol-chloroform DNA extraction followed by single tube nested PCR by the
      magnetic capture based DNA extraction followed by qPCR for molecular detection of
      E. multilocularis in definitive hosts.

PMID- 27884439
TI  - Genetic parameters for tick count and udder health in commercial and indigenous
      ewes in South Africa.
AB  - The genetics of tick infestation in sheep need study, as host resistance often
      forms part of integrated pest control programs. Repeated udder health scores,
      site-specific tick count, mating weight and reproduction records (N=879-1204)
      were recorded annually from 2010 to 2015 on ewes of the indigenous Namaqua
      Afrikaner (NA) fat-tailed breed, as well as the commercial Dorper and SA Mutton
      Merino (SAMM) breeds. Udders were scored subjectively on a 1-5 scale (1 - udder
      intact and 5 - udder damaged severely) and ticks were counted on three locations.
      The body sites counted were the head and thoracic limb (HTLTC), udder-pelvic limb
      (UPLTC) and perineum-breech-tail (PBTTC). These counts were also totaled for a
      total tick count (TTC). Reproduction traits were number of lambs weaned per ewe
      lambed and total weight of lamb weaned per ewe lambed. Udder health scores of NA
      ewes were lower than those of Dorpers, which in turn had lower scores than SAMM
      ewes. NA ewes had lower values for HTLTC, UPLTC and TTC than the commercial
      breeds, but higher values for PBTTC than Dorpers. Heritability estimates amounted
      to 0.26+/-0.04 for HTLTC, 0.53+/-0.04 for UPLTC, 0.07+/-0.06 for PBTTC, 0.44+/
      0.06 for TTC and 0.61+/-0.03 for udder health score. Animal permanent environment
      also affected PBTTC (0.14+/-0.07). Significant genetic correlations were found
      between the HTLTC and UPLTC (0.47+/-0.10), UPLTC and udder health score (0.52+/
      0.07), HTLTC and UPLTC (0.24+/-0.11) as well as UPLTC and PBTTC (-0.44+/-0.11).
      Heavier ewes had higher UPLTC (0.38+/-0.09), TTC (0.33+/-0.09) and impaired udder
      health (0.21+/-0.08). Udder health scores and tick counts at all sites were not
      related to reproduction traits. The indigenous NA breed outperformed the
      commercial breeds with lower values for HTLTC, UPLTC, TTC and a better udder
      health score. Mechanisms contributing to the better performance of the NA breed
      under pastoral conditions and the scope for selection for tick tolerance within
      breeds should be studied further.

PMID- 27884438
TI  - Toxoplasma gondii in stranded marine mammals from the North Sea and Eastern
      Atlantic Ocean: Findings and diagnostic difficulties.
AB  - The occurrence of the zoonotic protozoan parasite Toxoplasma gondii in marine
      mammals remains a poorly understood phenomenon. In this study, samples from 589
      marine mammal species and 34 European otters (Lutra lutra), stranded on the
      coasts of Scotland, Belgium, France, The Netherlands and Germany, were tested for
      the presence of T. gondii. Brain samples were analysed by polymerase chain
      reaction (PCR) for detection of parasite DNA. Blood and muscle fluid samples were
      tested for specific antibodies using a modified agglutination test (MAT), a
      commercial multi-species enzyme-linked immunosorbent assay (ELISA) and an
      immunofluorescence assay (IFA). Out of 193 animals tested by PCR, only two
      harbour porpoise (Phocoena phocoena) cerebrum samples, obtained from animals
      stranded on the Dutch coast, tested positive. The serological results showed a
      wide variation depending on the test used. Using a cut-off value of 1/40 dilution
      in MAT, 141 out of 292 animals (41%) were positive. Using IFA, 30 out of 244
      tested samples (12%) were positive at a 1/50 dilution. The commercial ELISA
      yielded 7% positives with a cut-off of the sample-to-positive (S/P) ratio>=50;
      and 12% when the cut-off was set at S/P ratio>=20. The high number of positives
      in MAT may be an overestimation due to the high degree of haemolysis of the
      samples and/or the presence of lipids. The ELISA results could be an
      underestimation due to the use of a multispecies conjugate. Our results confirm
      the presence of T. gondii in marine mammals in The Netherlands and show exposure
      to the parasite in both the North Sea and the Eastern Atlantic Ocean. We also
      highlight the limitations of the tests used to diagnose T. gondii in stranded
      marine mammals.

PMID- 27884440
TI  - Re-infection with Fasciola gigantica 6-month post-treatment with triclabendazole
      in cattle from mobile pastoralist husbandry systems at Lake Chad.
AB  - At Lake Chad in central Africa, livestock fascioliasis caused by Fasciola
      gigantica represents a major veterinary health problem, particularly in cattle
      reared in mobile pastoralist husbandry systems. We assessed re-infection after a
      single dose of triclabendazole with fascioliasis in cattle in a mobile
      pastoralist setting towards the end of the dry season. Within the cattle herds of
      14 groups of mobile pastoralists, 375 cattle were randomly selected. A faecal
      sample was obtained from each animal to determine the prevalence of F. gigantica.
      Animals were administered a single oral dose of triclabendazole (12mg/kg). A
      second faecal sample was obtained 6-month post-treatment after cattle had
      returned from the annual migration cycle. Faecal samples were fixed in sodium
      acetate-acetic acid-formalin (SAF), and examined for F. gigantica using the
      sedimentation technique. From the 375 cattle enrolled at baseline, 198 animals
      (53%) in 12 groups of mobile pastoralists were re-sampled at the 6-month follow
      up. Baseline prevalence did not differ noteworthy between animals lost to follow
      up and those re-examined. At baseline, bovine fascioliasis prevalence in cattle
      with follow-up data was 41.9% (95% confidence interval (CI) 35.2-48.9%). At the 6
      month post-treatment follow-up, the prevalence was 46.0% (95% CI 39.2-52.9%),
      ranging between 0% and 75% at the herd level. The mean faecal egg counts at the
      unit of the herd were higher at follow-up compared to baseline. The observed
      persistent high prevalence of F. gigantica infection in cattle shows that a
      single pre-rainy season treatment does not prevent rapid re-infection despite the
      partial migration away from the high-risk areas at Lake Chad into drier areas. A
      locally adapted strategic control package for fascioliasis in cattle in the Lake
      Chad area ought to integrate targeted triclabendazole treatment and seasonal
      transhumance practices.

PMID- 27884441
TI  - Trypanosoma vivax in water buffalo of the Venezuelan Llanos: An unusual outbreak
      of wasting disease in an endemic area of typically asymptomatic infections.
AB  - Trypanosoma vivax has been associated with asymptomatic infections in African and
      South American buffalo. In this study, T. vivax was analyzed in water buffalo
      (Bubalus bubalis) from Venezuela in a molecular survey involving 293 blood
      samples collected from 2006 to 2015 across the Llanos region. Results
      demonstrated constant infections (average 23%) during the years analyzed. In
      general, animals were healthy carriers of T. vivax with low levels of parasitemia
      and were diagnosed exclusively by TviCATL-PCR. However, an outbreak of severe
      acute infections mostly in dairy animals was reported during a prolonged drought
      affecting 30.4% of a buffalo herd (115 animals examined). During the outbreak,
      animals exhibiting anemia and neurological disorders developed fatal infections,
      and 7% of the herd died within nine months before treatment against
      trypanosomosis. Microsatellite locus genotyping (MLG) of T. vivax samples before
      and during the outbreak revealed similar genotypes, but outbreak isolates
      exhibited the most divergent MLG. Venezuelan samples from symptomless and sick
      buffalo did not share the MLGs previously detected in asymptomatic Brazilian
      buffalo. Trypanosoma evansi was not detected in the herd examined during the
      outbreak. However, as expected Babesia sp. (62.6%) and Anaplasma sp. (55.6%)
      infections were highly prevalent in asymptomatic buffalo in the studied areas.
      This is the first South American outbreak of highly lethal acute T. vivax
      infections in water buffalo. Our results suggest that chronically infected and
      asymptomatic buffalo living in areas of enzootic equilibrium can develop
      symptomatic/lethal disease triggered by stressful scarcity of green forage and
      water during long droughts, inappropriate management of herds and likely
      concomitant anaplasmosis and babesiosis. Altogether, these factors weaken buffalo
      immune defenses, allowing T. vivax to proliferate and, consequently, allowing for
      progression to wasting disease.

PMID- 27884442
TI  - The induction of the collagen capsule synthesis by Trichinella spiralis is
      closely related to protease-activated receptor 2.
AB  - The muscle-stage larvae of the parasite Trichinella spiralis have the ability to
      survive within host muscle tissue by virtue of the formation a nurse cell
      parasite complex, which is surrounded by collagen. The formation of the complex
      is initiated by excretory-secretory (ES) proteins produced by the parasite. To
      determine the mechanisms underlying collagen capsule formation, we investigated
      the expression levels of several types of collagen genes and TGF-betaI signaling
      related genes (Smad2 and Smad3) in muscle cells. Synthesis of type I, IV, and VI
      collagen, which are major constituents of the collagen capsule, significantly
      increased during T. spiralis infection. In addition, we found that expression of
      the protease-activated receptor 2 (PAR2) gene was significantly increased during
      this period. Expression levels of the collagen genes and TGF-betaI, Smad2, and
      Smad3 were induced by ES proteins and a PAR2 agonist, whereas their enhanced
      expression levels were reduced by a PAR2 antagonist and serine protease
      inhibitors. To evaluate the involvement of PAR2 during T. spiralis infection in
      vivo, we infected wild-type and PAR2 knockout (KO) mice with T. spiralis.
      Expression levels of type I, IV, and VI collagen genes and TGF-betaI signaling
      related genes (Smad2 and Smad3) were also decreased in the PAR2 KO mice.
      Phosphorylation of Smad2/3, which was increased by T. spiralis infection, was
      significantly diminished in the PAR2 KO mice. In conclusion, ES proteins
      containing serine protease most likely activate collagen synthesis via PAR2 and
      TGF-betaI signaling, and this event could influence collagen capsule formation.

PMID- 27884443
TI  - Effect of uncertainty in total parasite infestation on accuracy and precision of
      estimates of ectoparasiticide efficacy.
AB  - In animal studies of ectoparasiticide efficacy the total number of parasites with
      which experimental animals are infested is not always equal to the intended
      number of parasites (usually n=50 per experimental animal in the case of ticks,
      and n=50 or n=100 in the case of fleas). That is, in the practical implementation
      of a study protocol, the infestation of experimental animals may be subject to
      variability so that total infestation is not known precisely. The purpose of the
      present study is to assess the impact of this variability on the accuracy and
      precision of efficacy estimates. The results of a thorough simulation study show
      clearly that uncertainty in total parasite infestation - of the magnitude
      encountered in well-controlled animal studies - has virtually no effect on the
      accuracy and precision of estimators of ectoparasiticide efficacy.

PMID- 27884444
TI  - Dynamics of Parascaris and Strongylus spp. parasites in untreated juvenile
      horses.
AB  - Parasite control in foals is of utmost importance due to the high susceptibility
      to parasitic infection and disease in this age group. Foals are commonly co
      infected with strongyle and ascarid parasites, which complicate parasite control
      strategies. The present study retrospectively investigated necropsy records of
      foals born into a university herd kept without anthelmintic treatment since 1979.
      The aims were to statistically analyze the relationship between fecal egg counts,
      worm burdens, foal age, sex, and season with specific focus on Parascaris and
      Strongylus spp. A total of 83 foals born between 1999 and 2015 were included.
      Foals were born between January and September within the given year and age at
      necropsy ranged between 27 and 563 days of age with a mean and median of 202 and
      204 days, respectively. One set of multivariate mixed linear models was
      constructed analyzing strongyle and ascarid fecal egg counts as outcome
      variables, and another set of analyses investigated the following worm counts as
      outcome variables: Intestinal Parascaris spp. counts (immatures and adults), S.
      vulgaris (migrating and intestinal stages), S. edentatus (migrating and
      intestinal stages). Both ascarid and strongyle egg counts were influenced
      significantly by differences between study years (p<0.05). In addition, total
      ascarid egg counts were statistically influenced by age (p=0.020) exhibiting a
      peak at four months of age and fillies had significantly higher ascarid worm
      burdens (p=0.043). Foal age had significant influences on intestinal counts of
      immature Parascaris spp. (p=0.034) and adult S. edentatus counts (p=0.028).
      Larval counts of S. edentatus were significantly associated with birth month
      (p=0.023), whereas counts of migrating S. vulgaris larvae were not statistically
      associated with any of the investigated covariates. This study provides novel
      information on the dynamics of important parasites in naturally infected foals.

PMID- 27884446
TI  - Multidisciplinary approach to optimize management of patients with chronic
      hepatitis C and alcoholic liver disease.

PMID- 27884447
TI  - Videolaryngoscope King VisionTM, an alternative in the intubation of the awake
      patient?

PMID- 27884445
TI  - Taenia hydatigena in pigs in Burkina Faso: A cross-sectional abattoir study.
AB  - Taenia hydatigena is a non-zoonotic cestode that has canines as definitive hosts
      and ruminants and pigs as intermediate hosts. In pigs, its presence causes cross
      reactivity in serological testing for Taenia solium cysticercosis. Therefore,
      knowledge on the occurrence of T. hydatigena is paramount for validly estimating
      the seroprevalence of T. solium cysticercosis in pigs. In a cross-sectional
      abattoir study, we estimated the prevalence of T. hydatigena in pigs slaughtered
      in Koudougou, Burkina Faso. Carcasses of 452 pigs were examined by investigators
      for perceived and suspected T. hydatigena cysticercus lesions in the abdominal
      cavity or on the surface of abdominal organs. Routine meat inspection was
      performed by local inspectors to identify T. solium cysticerci. All lesions were
      subjected to PCR-RFLP analysis in order to differentiate Taenia spp.
      Additionally, individual blood samples were examined for the presence of
      circulating cysticercus antigens using the B158/B60 Ag-ELISA. Perceived T.
      hydatigena cysticerci were found in 13 pigs, whereas meat inspectors found seven
      carcasses infected with T. solium cysticerci. All were confirmed by molecular
      analysis. Of pigs with other suspected lesions, mostly located in the liver, 27
      and six were found to harbour T. hydatigena and T. solium cysticerci,
      respectively. Overall, 8.8% of pigs (40/452) were found infected with T.
      hydatigena and 2.9% (13/452) with T. solium. Of these positive pigs, one was
      found infected with both Taenia spp. (0.2%, 1/452). Blood samples of 48.5% of
      pigs (219/452) were positive in the Ag-ELISA. Pigs with confirmed cysts of T.
      hydatigena and T. solium had a positive Ag-ELISA result in 57.5% (23/40) and
      61.5% (8/13) of cases, respectively. The observed T. hydatigena prevalence in
      this study is relatively high in comparison to other studies in Africa. Estimates
      of the occurrence of active porcine T. solium infection using the B158/B60 Ag
      ELISA should therefore be adjusted for the presence of T. hydatigena. The low
      level of T. solium infection detected upon meat inspection in this study is
      likely an underestimation of the true prevalence since routine meat inspection
      shows poor sensitivity and pigs perceived to be infected based on tongue
      palpation are rarely sent to official abattoirs.

PMID- 27884448
TI  - Sulodexide: A new antithrombotic agent.

PMID- 27884450
TI  - Rhythmic movement disorder in childhood: An integrative review.
AB  - Rhythmic movement disorder consists of repetitive stereotypic movements, such as
      head banging or body rocking, that recur every second or so and may last from a
      few minutes to hours, usually prior to sleep onset. This review of childhood
      rhythmic movement disorder highlights the lack of systematic research into core
      aspects of the condition, relying heavily on small case series or case reports.
      Interpretation is further limited by almost universal failure to confirm the core
      diagnostic criteria (C) of the International classification of sleep disorders
      (III), namely that the rhythmic movements should have clinical consequences.
      Nonetheless, a number of themes emerge. Rhythmic movement disorder is likely to
      start in infancy and have a developmental course with spontaneous resolution in
      early childhood in many cases. Factors associated with persistence are, however,
      unclear. Associations with ADHD and neurodevelopmental disorders are intriguing,
      require further study and may shed light on the underlying cause of the
      condition. There is a pressing need for a systematic approach to classify
      rhythmic movement disorder, to allow standardization of the much needed research
      into the underlying aetiology and treatment of this relatively neglected sleep
      disorder.

PMID- 27884449
TI  - Functional characterization and expression of GASCL1 and GASCL2, two anther
      specific chalcone synthase like enzymes from Gerbera hybrida.
AB  - The chalcone synthase superfamily consists of type III polyketidesynthases
      (PKSs), enzymes responsible for producing plant secondary metabolites with
      various biological and pharmacological activities. Anther-specific chalcone
      synthase-like enzymes (ASCLs) represent an ancient group of type III PKSs
      involved in the biosynthesis of sporopollenin, the main component of the exine
      layer of moss spores and mature pollen grains of seed plants. In the latter, ASCL
      proteins are localized in the tapetal cells of the anther where they participate
      in sporopollenin biosynthesis and exine formation within the locule. It is
      thought that the enzymes responsible for sporopollenin biosynthesis are highly
      conserved, and thus far, each angiosperm species with a genome sequenced has
      possessed two ASCL genes, which in Arabidopsis thaliana are PKSA and PKSB. The
      Gerbera hybrida (gerbera) PKS protein family consists of three chalcone synthases
      (GCHS1, GCHS3 and GCHS4) and three 2-pyrone synthases (G2PS1, G2PS2 and G2PS3).
      In previous studies we have demonstrated the functions of chalcone synthases in
      flavonoid biosynthesis, and the involvement of 2-pyrone synthases in the
      biosynthesis of antimicrobial compounds found in gerbera. In this study we
      expanded the gerbera PKS-family by functionally characterizing two gerbera ASCL
      proteins. In vitro enzymatic studies using purified recombinant proteins showed
      that both GASCL1 and GASCL2 were able to use medium and long-chain acyl-CoA
      starters and perform two to three condensation reactions of malonyl-CoA to
      produce tri- and tetraketide 2-pyrones, usually referred to as alpha-pyrones in
      sporopollenin literature. Both GASCL1 and GASCL2 genes were expressed only in
      floral organs, with most expression observed in anthers. In the anthers,
      transcripts of both genes showed strict tapetum-specific localization.

PMID- 27884451
TI  - Cholesterol-lowering pattern affects the progression of atherosclerosis in
      apolipoprotein E deficient mice.
AB  - Although the importance of LDL cholesterol lowering is widely recognized, the
      impact of the cholesterol-lowering pattern on the atherosclerosis remains
      unclear. Here, we used cholestyramine in apolipoprotein E deficient mice in two
      different regimens to induce a see-saw shaped or a sustained cholesterol
      reduction, with the trough of cholesterol comparable. After 12 weeks-treatment, a
      sustained cholesterol reduction exhibited a smaller atherosclerotic area.
      Moreover, we observed a correlation between the area under the curve of plasma
      cholesterol and the atherosclerotic area. These results suggest that the
      sustained cholesterol reduction is beneficial for preventing the progression of
      atherosclerosis in cholesterol lowering therapy.

PMID- 27884452
TI  - Factors associated with thrombotic complications in pediatric patients with
      vascular malformations.
AB  - BACKGROUND AND OBJECTIVES: Thrombosis is an uncommon disorder in children.
      Patients with slowflow vascular malformations have higher risk of developing
      localized intravascular coagulation, which is closely related to the presence of
      thrombotic events. These episodes cause pain, can be recurrent and determine a
      clear deterioration in the quality of life. Moreover, serious complications such
      as pulmonary thromboembolism and eventually death have been described. The aim of
      the present study is to identify clinical and laboratory risk factors associated
      with thrombotic events in pediatric patients with vascular malformations.
      METHODS: Case-Control study. Clinical records of patients who consulted the
      vascular anomalies study group (VASG). This group carries out interdisciplinary
      assessment of patients with vascular malformations. From June 2008 to December
      2014, 110 patients were assessed of whom 46 patients met the inclusion criteria,
      with half of them presenting a thrombotic complication and the others not, these
      latter serving as controls. Statistical analysis included multivariate logistic
      regression analysis to determine major risk factors for thrombosis. RESULTS: In
      the bivariate analysis we found a significant association between increased
      levels of Ddimer and thrombotic complications (OR 17.1 [95% CI 3.95-73.95;
      p<0.01]). In addition, a surface area>=10cm2 (OR 6.18 [95% CI 1.59-23.99;
      p<0.01]) and the presence of palpable phleboliths (OR 20.17 [95% CI 2.32-165.77;
      p<0.01]) were associated with a significant higher risk of thrombosis.
      Multivariate analysis identified older age (OR 1.33; p=0.013), a surface
      area>=10cm2 (OR 8.19; p=0.042) and palpable phleboliths (OR 85.29; p<0.01) as
      significant risk factors. CONCLUSIONS: Our study suggests the existence of
      clinical factors associated with higher risk of thrombotic complications, such as
      the extent of the malformation, palpable phleboliths and increased age among
      children with vascular malformations.

PMID- 27884453
TI  - A call for a standardized definition of perforated appendicitis.
AB  - BACKGROUND: Abscess rates have been reported to be as low as 1% and as high as
      50% following perforated appendicitis (PA). This range may be because of lack of
      universal definition for PA. An evidence-based definition (EBD) is crucial for
      accurate wound classification, risk-stratification, and subsequent process
      optimization. ACS NSQIP-Pediatric guidelines do not specify a definition of PA.
      We hypothesize that reported postoperative abscess rates underrepresent true
      incidence, as they may include low-risk cases in final calculations. METHODS:
      Local institutional records of PA patients were reviewed to calculate the
      postoperative abscess rate. The ACS NSQIP-Pediatric participant use file (PUF)
      was used to determine cross-institutional postoperative abscess rates. A PubMed
      literature review was performed to identify trials reporting PA abscess rates,
      and definitions and rates were recorded. RESULTS: 20.9% of our patients with PA
      developed a postoperative abscess. The ACS NSQIP-Pediatric abscess rate was
      significantly lower (7.61%, p<0.001). In the eighteen published studies analyzed,
      average abscess rate (14.49%) was significantly higher than ACS NSQIP-Pediatric
      (p<0.001). There was significantly more variation in trials that do not employ an
      EBD of perforation (Levene's test F-value =6.980, p=0.018). CONCLUSIONS: A
      standard EBD of perforation leads to lower variability in reported postoperative
      abscess rates following PA. Nonstandard definitions may be significantly altering
      the aggregate rate of postoperative abscess formation. We advocate for adoption
      of a standard definition by all institutions participating in ACS NSQIP-Pediatric
      data submission. LEVEL OF EVIDENCE: III.

PMID- 27884454
TI  - [Management of adverse effects related to human immunoglobulin therapy:
      Recommendations for clinical practice].
AB  - Both intravenous and subcutaneous immunoglobulins are therapeutic modalities
      approved in various conditions, including primary and secondary immune
      deficiencies and autoimmune disorders. To date, immunoglobulins have more often
      been considered as a safe medication, with minor adverse effects such as
      hypertension, fever and chills, nausea, myalgia or headache. However, with the
      wider use of immunoglobulins in the treatment of autoimmune diseases, severe side
      effects have also been reported to occur in immunoglobulin-treated patients,
      especially anaphylaxis, aseptic meningitis, acute renal impairment, thrombotic
      events as well as haematological manifestations. This paper reviews all the
      potential adverse events related to immunoglobulin therapy and establishes a
      comprehensive guideline for the management of these events.

PMID- 27884455
TI  - [Acid sphingomyelinase deficiency (Niemann-Pick disease type B) in adulthood: A
      retrospective multicentric study of 28 adult cases].
AB  - INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) is an autosomal recessive
      disease with a clinical spectrum ranging from a neurovisceral infantile form
      (Niemann-Pick disease type A) to a chronic visceral form also encountered in
      adults (Niemann-Pick disease type B, NP-B). METHODS: Retrospective multicentric
      analysis of French adult patients with ASMD over the period 1985-March 2015.
      Clinical, biological, and imaging data were analyzed. RESULTS: Twenty-eight
      patients (19 males, 9 females) were analyzed. Diagnosis was made before the age
      of 10 years in 16 cases. Main symptoms at diagnosis were spleen/liver enlargement
      and interstitial lung disease. Biological abnormalities included:
      thrombocytopenia (platelet count <150 000/mm3) in 24 cases including 4 patients
      with platelet count <60 000/mm3, constantly low high-density lipoprotein (HDL)
      cholesterol, polyclonal hypergammaglobulinemia (n=6), monoclonal gammopathy of
      unknown significance (n=5), normal prothrombin level discordant with low factor V
      (n=5), elevated chitotriosidase level (n=11). The diagnosis was confirmed in all
      cases by deficient acid sphingomyelinase enzyme activity. SMPD1 gene sequencing
      was performed in 25 cases. The frequent p.R610del mutation was largely
      predominant, constituting 62% of the non-related alleles. During the follow-up
      period, three patients died before 50 years of age from cirrhosis, heart failure
      and lung insufficiency, respectively. CONCLUSION: ASMD in adulthood (NP-B)
      associates spleen/liver enlargement and interstitial lung disease. Early
      diagnosis and appropriate management are essential for reducing the risk of
      complications, improving quality of life, and avoiding inappropriate procedures
      such as splenectomy. To date, only symptomatic therapy is available. A phase 2/3
      therapeutic trial with IV infusion of recombinant enzyme is on-going.

PMID- 27884457
TI  - [Abdominal pain and vomiting in a 66-year-old man].

PMID- 27884456
TI  - [Neurosarcoidosis: Diagnosis and therapeutic issues].
AB  - Neurological localizations of sarcoidosis are heterogeneous and may affect
      virtually every part of the central or peripheral nervous system. They are often
      the inaugural manifestation of sarcoidosis. The diagnosis may be difficult due to
      the lack of extra-neurological localization. Diagnosis may be discussed in the
      presence of an inflammatory neurological disease, in particular in case of
      suggestive radiological or biological pattern. Cerebrospinal fluid analysis shows
      lymphocytic pleiocytosis, often with low glucose level. The diagnosis relies on a
      clinical, biological and radiological presentation consistent with
      neurosarcoidosis, the presence of non-caseating granuloma and exclusion of
      differential diagnoses. Screening for other localizations of sarcoidosis, in
      particular cardiac disease may be obtained during neurosarcoidosis. The treatment
      of neurosarcoidosis relies on corticosteroids although immunosuppressive drugs
      are usually added because of the chronic course of this condition and to limit
      the side effects of steroids. Treatments and follow-up may be prolonged because
      of the high rate of relapses.

PMID- 27884458
TI  - Risk of Carotid Stroke after Chiropractic Care: A Population-Based Case-Crossover
      Study.
AB  - BACKGROUND: Chiropractic manipulation is a popular treatment for neck pain and
      headache, but may increase the risk of cervical artery dissection and stroke.
      Patients with carotid artery dissection can present with neck pain and/or
      headache before experiencing a stroke. These are common symptoms seen by both
      chiropractors and primary care physicians (PCPs). We aimed to assess the risk of
      carotid artery stroke after chiropractic care by comparing association between
      chiropractic and PCP visits and subsequent stroke. METHODS: A population-based,
      case-crossover study was undertaken in Ontario, Canada. All incident cases of
      carotid artery stroke admitted to hospitals over a 9-year period were identified.
      Cases served as their own controls. Exposures to chiropractic and PCP services
      were determined from health billing records. RESULTS: We compared 15,523 cases to
      62,092 control periods using exposure windows of 1, 3, 7, and 14 days prior to
      the stroke. Positive associations were found for both chiropractic and PCP visits
      and subsequent stroke in patients less than 45 years of age. These associations
      tended to increase when analyses were limited to visits for neck pain and
      headache-related diagnoses. There was no significant difference between
      chiropractic and PCP risk estimates. We found no association between chiropractic
      visits and stroke in those 45 years of age or older. CONCLUSIONS: We found no
      excess risk of carotid artery stroke after chiropractic care. Associations
      between chiropractic and PCP visits and stroke were similar and likely due to
      patients with early dissection-related symptoms seeking care prior to developing
      their strokes.

PMID- 27884459
TI  - Balance evaluation techniques and physical therapy in post-stroke patients: A
      literature review.
AB  - A stroke (cerebrovascular accident - CVA) is a significant social-economic issue.
      Approximately 15-30% of all patients develop life-long disability, 20% require
      over 3 months of specialized care in healthcare institutions, and the majority of
      the patients never recover the ability to maintain a proper vertical position.
      Such CVA sequelae as balance disturbances not only negatively affect patients'
      daily physical activity, but also result in social isolation. A number of
      standardized clinical scales, tests, and instrumental examination techniques have
      been proposed for evaluating not only post-CVA balance function, but also any
      changes in this function following various interventions. Even though scientific
      literature lists numerous methods and instruments for the improvement of balance
      after a CVA, not all of them are equally effective, and there have been rather
      controversial evaluations of some techniques. Nevertheless, the application of
      the majority of the techniques as complementary or alternative measures to
      traditional physical therapy (PT) frequently yields better results.

PMID- 27884460
TI  - Endogenous spinal cord stem cells in multiple sclerosis and its animal model.
AB  - The adult mammalian spinal cord (SC) harbors neural stem cells (NSCs). The SC
      NSCs are mostly quiescent during physiological conditions but are quickly
      activated in traumatic injury models. The SC-NSCs generate mostly glia, but are
      able to differentiate into neurons when affected by favourable conditions. An
      example is the inflammatory milieu in the SC of rat EAE, where the SC-NSCs
      migrate into demyelinated lesions and give rise to both glia and neurons. In MS,
      cells with progenitor phenotypes accumulate in inflammatory lesions both in brain
      and SC, but the extent to which these cells contribute to repair remains to be
      revealed.

PMID- 27884461
TI  - Reactivity to social stress in ethnic minority men.
AB  - Repeated exposures to social exclusion, through a process of sensitization, may
      result in larger responses to experiences of social stress. The current study
      tested the hypothesis that healthy Moroccan-Dutch men respond stronger to social
      stress than Dutch controls 1) in daily life, and 2) in an experimental set-up. A
      general population sample of 50 Moroccan-Dutch and 50 Dutch young adult males
      were tested with 1) the Experience Sampling Method, a structured diary technique,
      assessing reactivity to social stress in daily life, and 2) an experimental
      exposure to social peer evaluation. No group differences were found in affective
      or psychotic reactivity to daily social stress. When exposed to a negative social
      evaluation in the lab, a blunted affective response was found in the Moroccan
      Dutch compared to the Dutch group, whereas the psychotic response did not differ
      significantly between groups. In conclusion, healthy Moroccan-Dutch men are not
      more sensitive to social stress than healthy Dutch men. Instead, the blunted
      affective response of Moroccan-Dutch men to peer evaluation may signify
      habituation rather than sensitization.

PMID- 27884462
TI  - Dual Neural Network Model for the Evolution of Speech and Language.
AB  - Explaining the evolution of speech and language poses one of the biggest
      challenges in biology. We propose a dual network model that posits a volitional
      articulatory motor network (VAMN) originating in the prefrontal cortex (PFC;
      including Broca's area) that cognitively controls vocal output of a
      phylogenetically conserved primary vocal motor network (PVMN) situated in
      subcortical structures. By comparing the connections between these two systems in
      human and nonhuman primate brains, we identify crucial biological preadaptations
      in monkeys for the emergence of a language system in humans. This model of
      language evolution explains the exclusiveness of non-verbal communication sounds
      (e.g., cries) in infants with an immature PFC, as well as the observed emergence
      of non-linguistic vocalizations in adults after frontal lobe pathologies.

PMID- 27884463
TI  - Gated carbon-ion scanning treatment for pancreatic tumour with field specific
      target volume and organs at risk.
AB  - OBJECTIVE: To assess the feasibility of treatment planning for pancreatic tumours
      subject to respiratory motion using field-specific target volumes (FTV) and field
      specific organs at risk (FOAR) using four-dimensional computed tomography (4DCT).
      METHODS: Fourteen pancreatic cancer patients underwent 4DCT. Radiation
      oncologists contoured the gross tumour volume (GTV), clinical target volume
      (CTV), spinal cord, duodenum, kidneys, and stomach. The gating duty cycle was set
      to 30 % around exhalation. FTV and FOAR were calculated using the 4DCT dataset.
      Planning target volumes (PTV) and planning organs at risk volumes (PRV) were
      defined as equal to FTV and FOAR, respectively. A dose of 55.2Gy relative
      biological effectiveness (RBE) was planned to target the PTV from four beam
      angles. A single field uniform dose (SFUD) plan was selected. The dose
      distribution, including intrafractional motion changes, was generated. RESULTS:
      The mean volume of target receiving 95 % of the planned doses was 96.4+/-4.1 % to
      the GTV and 94.7+/-0.9 % to the CTV. The highest dose to 2cc of duodenal volume
      was 27.5Gy (RBE). The volume of the stomach receiving ?30Gy (RBE) was <7.0cc in
      all patients. All metrics for OARs satisfied dose constraints. CONCLUSION: Dose
      to the CTV was covered sufficiently by the 4DCT-generated FTV, and dose to OARs
      was reduced by 4DCT-generated FOAR. This methodology may prevent adverse
      reactions while preserving local tumour control.

PMID- 27884464
TI  - Estimating the Area Under ROC Curve When the Fitted Binormal Curves Demonstrate
      Improper Shape.
AB  - RATIONALE AND OBJECTIVES: The "binormal" model is the most frequently used tool
      for parametric receiver operating characteristic (ROC) analysis. The binormal ROC
      curves can have "improper" (non-concave) shapes that are unrealistic in many
      practical applications, and several tools (eg, PROPROC) have been developed to
      address this problem. However, due to the general robustness of binormal ROCs,
      the improperness of the fitted curves might carry little consequence for
      inferences about global summary indices, such as the area under the ROC curve
      (AUC). In this work, we investigate the effect of severe improperness of fitted
      binormal ROC curves on the reliability of AUC estimates when the data arise from
      an actually proper curve. MATERIALS AND METHODS: We designed theoretically proper
      ROC scenarios that induce severely improper shape of fitted binormal curves in
      the presence of well-distributed empirical ROC points. The binormal curves were
      fitted using maximum likelihood approach. Using simulations, we estimated the
      frequency of severely improper fitted curves, bias of the estimated AUC, and
      coverage of 95% confidence intervals (CIs). In Appendix S1, we provide additional
      information on percentiles of the distribution of AUC estimates and bias when
      estimating partial AUCs. We also compared the results to a reference standard
      provided by empirical estimates obtained from continuous data. RESULTS: We
      observed up to 96% of severely improper curves depending on the scenario in
      question. The bias in the binormal AUC estimates was very small and the coverage
      of the CIs was close to nominal, whereas the estimates of partial AUC were biased
      upward in the high specificity range and downward in the low specificity range.
      Compared to a non-parametric approach, the binormal model led to slightly more
      variable AUC estimates, but at the same time to CIs with more appropriate
      coverage. CONCLUSIONS: The improper shape of the fitted binormal curve, by
      itself, ie, in the presence of a sufficient number of well-distributed points,
      does not imply unreliable AUC-based inferences.

PMID- 27884465
TI  - Crossing the Chasm(s): Demonstrating the Clinical Value of Hyperpolarized Gas
      MRI.

PMID- 27884466
TI  - Linking pollutant exposure of humpback whales breeding in the Indian Ocean to
      their feeding habits and feeding areas off Antarctica.
AB  - Humpback whales, Megaptera novaeangliae, breeding off la Reunion Island (Indian
      Ocean) undergo large-scale seasonal migrations between summer feeding grounds
      near Antarctica and their reproductive winter grounds in the Indian Ocean. The
      main scope of the current study was to investigate chemical exposure of humpback
      whales breeding in the Indian Ocean by providing the first published data on this
      breeding stock concerning persistent organic pollutants (POPs), namely
      polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), hexachlorocyclohexanes
      (HCHs), DDT and its metabolites (DDTs), chlordane compounds (CHLs),
      polybrominated diphenyl ethers (PBDEs), and methoxylated PBDEs (MeO-PBDEs).
      Analyses of stable isotopes delta13C and delta15N in skin resulted in further
      insight in their feeding ecology, which was in agreement with a diet focused
      mainly on low trophic level prey species, such as krill from Antarctica. POPs
      were measured in all humpback whales in the order of HCB > DDTs > CHLs > HCHs >
      PCBs > PBDEs > MeO-BDEs. HCB (median: 24 ng g-1 lw) and DDTs (median: 7.7 ng g-1
      lw) were the predominant compounds in all whale biopsies. Among DDT compounds,
      p,p'-DDE was the major organohalogenated pollutant, reflecting its long-term
      accumulation in humpback whales. Significantly lower concentrations of HCB and
      DDTs were found in females than in males (p < 0.001). Other compounds were
      similar between the two genders (p > 0.05). Differences in the HCB and DDTs
      suggested gender-specific transfer of some compounds to the offspring. POP
      concentrations were lower than previously reported results for humpback whales
      sampled near the Antarctic Peninsula, suggesting potential influence of their
      nutritional status and may indicate different exposures of the whales according
      to their feeding zones. Further investigations are required to assess exposure of
      southern humpback whales throughout their feeding zones.

PMID- 27884468
TI  - Corrigendum to "Endosulfan, pentachlorobenzene and short-chain chlorinated
      paraffins in background soils from Western Europe" [Environ. Pollut. 196 (2015),
      21-28].

PMID- 27884467
TI  - Elucidating ozonation mechanisms of organic micropollutants based on DFT
      calculations: Taking sulfamethoxazole as a case.
AB  - Ozonation is widely used in wastewater treatment plants to remove diverse organic
      micropollutants. As molecular structures of organic micropollutants contain
      multiple ozone-preferred reaction sites, and moreover intermediate products can
      react with ozone again, ozonation mechanism is complex. A fast increasing number
      of organic micropollutants and a great demand of ecological risk assessments call
      for an in silico method to provide insights into the ozonation mechanism of
      organic micropollutants. Here, an in silico model was developed to unveil
      ozonation mechanisms of organic micropollutants. Sulfamethoxazole was taken as a
      case. The model enumerates elementary reactions following well-accepted ozonation
      patterns and secondary transformation reactions established for intermediates by
      experiments. Density functional theory (DFT) calculations were employed for
      evaluating thermodynamic feasibilities of reaction pathways. By calculating Gibbs
      free energies, ozonation products of SMX were predicted. The predicted products
      are consistent with those detected in experiments. This method is advanced in
      revealing all possible reaction pathways including minor pathways that produce
      toxic byproducts but are difficult to be observed by experiments. Accordingly,
      water treatment engineers can setup necessary treatment technology to ensure
      water safety.

PMID- 27884469
TI  - Chinese province-scale source apportionments for sulfate aerosol in 2005
      evaluated by the tagged tracer method.
AB  - Appropriate policies to improve air quality by reducing anthropogenic emissions
      are urgently needed. This is typified by the particulate matter (PM) problem and
      it is well known that one type of PM, sulfate aerosol (SO42-), has a large-scale
      impact due to long range transport. In this study we evaluate the source-receptor
      relationships of SO42- over East Asia for 2005, when anthropogenic sulfur dioxide
      (SO2) emissions from China peaked. SO2 emissions from China have been declining
      since 2005-2006, so the possible maximum impact of Chinese contributions of SO42-
      is evaluated. This kind of information provides a foundation for policy making
      and the estimation of control effects. The tagged tracer method was applied to
      estimate the source apportionment of SO42- for 31 Chinese province-scale regions.
      In addition, overall one-year source apportionments were evaluated to clarify the
      seasonal dependency. Model performance was confirmed by comparing with ground
      based observations over mainland China, Taiwan, Korea, and Japan, and the model
      results fully satisfied the performance goal for PM. We found the following
      results. Shandong and Hebei provinces, which were the largest and second largest
      SO2 sources in China, had the greatest impact over the whole of East Asia with
      apportionments of around 10-30% locally and around 5-15% in downwind receptor
      regions during the year. Despite large SO2 emissions, the impact of south China
      (e.g., Guizhou, Guangdong, and Sichuan provinces) was limited to local impact.
      These results suggest that the reduction policy in south China contributes to
      improving the local air quality, whereas policies in north and central China are
      beneficial for both the whole of China and downwind regions. Over Taiwan, Korea,
      and Japan, the impact of China was dominant; however, local contributions were
      important during summer.

PMID- 27884470
TI  - The first exposure assessment of legacy and unrestricted brominated flame
      retardants in predatory birds of Pakistan.
AB  - The exposure to legacy polybrominated diphenyl ethers (PBDEs),
      hexabromocyclododecanes (HBCDDs) and unrestricted 1,2-bis (2,4,6-tribromophenoxy)
      ethane (BTBPE), bis (2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEH-TEBP) and 2
      ethylhexyl-2,3,4,5-tetrabromo-benzoate (EH-TBB) was examined in tail feathers of
      76 birds belonging to ten predatory species inhabiting Pakistan. In addition,
      different feather types of six individuals of Black kite (Milvus migrans) were
      compared for their brominated flame retardant (BFR) levels. Black kite was found
      to be the most contaminated species with a median (minimum-maximum) tail feather
      concentration of 2.4 (0.70-7.5) ng g-1 dw for ?PBDEs, 1.5 (0.5-8.1) ng g-1 dw for
      ?HBCDDs and 0.10 (<LOQ-0.1) ng g-1 dw for BTBPE. Among unrestricted BFRs, BTBPE
      was detected only in Black kite and Little owl (Athene noctua), whereas BEH-TEBP
      and EH-TBB were not detected in any species. BDE-47 was found to be the most
      prevalent BFR compound in aquatic species, while BDE-99 and -153 were more
      abundant in terrestrial species. For HBCDDs, alpha-isomer was generally recorded
      as the most prevalent BFR in both terrestrial and aquatic species. The
      concentrations of BFRs differed significantly (all P < 0.01) among species,
      trophic guilds and between habitats, the latter for PBDEs only (P < 0.04),
      whereas differences among taxonomic affiliations and groups with different
      feeding regimes were not significant (P > 0.05 for both). Similarly, no
      significant concentration differences were observed among different feather types
      (all P > 0.05) suggesting their similar exposure. While variables such as
      species, trophic guild and delta15N values were evaluated as major predictors for
      BFR accumulation in the studied species, we predict that combined effects of just
      mentioned factors may govern the intra- and interspecific differences in BFR
      contamination profiles. We urge for further investigation of BFR exposure and
      potential toxicological effects in predatory birds from Asia with a more
      extensive sample size per species and location.

PMID- 27884471
TI  - Polybrominated diphenyl ethers (PBDES) and hexa-brominated biphenyls (Hexa-BBs)
      in fresh foods ingested in Taiwan.
AB  - Polybrominated diphenyl ethers (PBDEs) and hexa-brominated biphenyls (Hexa-BBs)
      are bioaccumulative and aggregate in the food chain. Therefore, background
      monitoring and risk assessment for dietary intake are necessary. In present
      study, a systematic sampling method was first used to collect the high fat
      content foodstuff such as poultry, livestock, eggs, fish, other seafood, dairy
      products, and the infant foods and then foodstuff with high consumption in seven
      categories of 600 food samples. After integrating four years of background
      surveys of PBDE levels (2010-2013) and one year of that of Hexa-BBs (2013), the
      highest estimated daily intake (EDI) of PBDEs for Taiwanese food consumption was
      found in 0- to 3-year-olds (mean = 9.38 ng kg-1 bw d-1, the 95% upper limit of
      Monte Carlo Simulation (MCS P95) was 21.52 ng kg-1 bw d-1), and the lowest in 16-
      to 18-year-old girls (mean = 3.35 ng kg-1 bw d-1, MCS P95 was 6.53 ng kg-1 bw d
      1). Moreover, the highest of EDI of Hexa-BBs was found in 0-3 years old (mean =
      0.007 ng kg-1 bw d-1, MCS P95 = 0.019 ng kg-1 bw d-1), and lowest in 17-18 years
      old female (mean = 0.002 ng/kg/day, MCS P95 = 0.005 ng kg-1 bw d-1). This study
      suggests that the large MOEs (>2.5) for the four important congeners BDE-47, -99,
      -153, and -209, indicate that the dietary exposures are not probably a
      significant health concern for Taiwanese.

PMID- 27884472
TI  - Impact of untreated wastewater on a major European river evaluated with a
      combination of in vitro bioassays and chemical analysis.
AB  - Complex mixtures of micropollutants, including pesticides, pharmaceuticals and
      industrial chemicals emitted by wastewater effluents to European rivers may
      compromise the quality of these water resources and may pose a risk to ecosystem
      health and abstraction of drinking water. In the present study, an integrated
      analytical and bioanalytical approach was applied to investigate the impact of
      untreated wastewater effluents from the city of Novi Sad, Serbia, into the River
      Danube. The study was based on three on-site large volume solid phase extracted
      water samples collected upstream and downstream of the untreated wastewater
      discharge. Chemical screening with liquid chromatography high resolution mass
      spectrometry (LC-HRMS) was applied together with a battery of in vitro cell-based
      bioassays covering important steps of the cellular toxicity pathway to evaluate
      effects on the activation of metabolism (arylhydrocarbon receptor AhR, peroxisome
      proliferator activated receptor gamma PPARgamma), specific modes of action
      (estrogen receptor ERalpha, androgen receptor AR) and adaptive stress responses
      (oxidative stress, inflammation). Increased effects, significantly changed
      contamination patterns and higher chemical concentrations were observed
      downstream of the wastewater discharge. A mass balance approach showed that
      enhanced endocrine disruption was in good agreement with concentrations of
      detected hormones, while only a smaller fraction of the effects on xenobiotic
      metabolism (<1%) and adaptive stress responses (0-12%) could be explained by the
      detected chemicals. The chemical and effects patterns observed upstream of the
      discharge point were fairly re-established at about 7 km downstream,
      demonstrating the enormous dilution capacity of this large river.

PMID- 27884473
TI  - ICU ward design and nosocomial infection rates: a cross-sectional study in
      Germany.
AB  - BACKGROUND: There is increasing interest in the effects of hospital and ward
      design on multi-faceted infection control. Definitive evidence is rare and the
      state of knowledge about current ward design is lacking. OBJECTIVE: To collect
      data on the current status of ward design for intensive care units (ICUs) and to
      analyse associations between particular design factors and nosocomial infection
      rates. METHODS: In 2015, operational infrastructure data were collected via an
      online questionnaire from ICUs participating voluntarily in the German nosocomial
      infection surveillance system (KISS). A multi-variate analysis was subsequently
      undertaken with nosocomial infection rates from the KISS database from 2014 to
      2015. FINDINGS: In total, 534 ICUs submitted data about their operational
      infrastructure. Of these, 27.1% of beds were hosted in single-bed rooms with a
      median size of 18m2 (interquartile range 15-21m2), and 73.5% of all ICU beds had
      a hand rub dispenser nearby. The authors were able to match 266 ICUs in the multi
      variate analysis. ICUs with openable windows in patient rooms were associated
      with lower device-associated lower respiratory tract infections [odds ratio (OR)
      0.73, 95% confidence interval (CI) 0.58-0.90]. ICUs with >40% two-bed rooms were
      associated with lower primary bloodstream infection rates (OR 0.66, 95% CI 0.51
      0.86). CONCLUSION: Only minor associations were found between design factors and
      ICU infection rates. Most were surrogates for other risk factors.

PMID- 27884474
TI  - CKD and Risk for Hospitalization With Infection: The Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - BACKGROUND: Individuals on dialysis therapy have a high risk for infection, but
      risk for infection in earlier stages of chronic kidney disease has not been
      comprehensively described. STUDY DESIGN: Observational cohort study. SETTING &
      PARTICIPANTS: 9,697 participants (aged 53-75 years) in the Atherosclerosis Risk
      in Communities (ARIC) Study. Participants were followed up from 1996 to 1998
      through 2011. PREDICTORS: Estimated glomerular filtration rate (eGFR) and urinary
      albumin-creatinine ratio (ACR). OUTCOMES: Risk for hospitalization with infection
      and death during or within 30 days of hospitalization with infection. RESULTS:
      During follow-up (median, 13.6 years), there were 2,701 incident hospitalizations
      with infection (incidence rate, 23.6/1,000 person-years) and 523 infection
      related deaths. In multivariable analysis, HRs of incident hospitalization with
      infection as compared to eGFRs>=90mL/min/1.73m2 were 2.55 (95% CI, 1.43-4.55),
      1.48 (95% CI, 1.28-1.71), and 1.07 (95% CI, 0.98-1.16) for eGFRs of 15 to 29, 30
      to 59, and 60 to 89mL/min/1.73m2, respectively. Corresponding HRs were 3.76 (95%
      CI, 1.48-9.58), 1.62 (95% CI, 1.20-2.19), and 0.99 (95% CI, 0.80-1.21) for
      infection-related death. Compared to ACRs<10mg/g, HRs of incident hospitalization
      with infection were 2.30 (95% CI, 1.81-2.91), 1.56 (95% CI, 1.36-1.78), and 1.34
      (95% CI, 1.20-1.50) for ACRs>=300, 30 to 299, and 10 to 29mg/g, respectively.
      Corresponding HRs were 3.44 (95% CI, 2.28-5.19), 1.57 (95% CI, 1.18-2.09), and
      1.39 (95% CI, 1.09-1.78) for infection-related death. Results were consistent
      when separately assessing risk for pneumonia, kidney and urinary tract
      infections, bloodstream infections, and cellulitis and when taking into account
      recurrent episodes of infection. LIMITATIONS: Outcome ascertainment relied on
      diagnostic codes at time of discharge. CONCLUSIONS: Increasing provider awareness
      of chronic kidney disease as a risk factor for infection is needed to reduce
      infection-related morbidity and mortality.

PMID- 27884476
TI  - Systemic immunization with rPotD reduces Streptococcus pneumoniae nasopharyngeal
      colonization in mice.
AB  - Streptococcus pneumoniae (pneumococcus) is a human pathogen that can cause otitis
      media, pneumonia and, in severe cases, meningitis and bacteremia. The
      pneumococcus expresses PotD, a protein belonging to the polyamines transporter
      complex called PotABCD. PotD is a membrane-associated protein that binds
      polyamines and has been shown to be important for virulence. In this work we
      demonstrate that subcutaneous immunization with rPotD reduces the bacterial load
      in the nasal tissue of mice, following intranasal challenge with a type 6B
      pneumococcus. The protective effect correlated with the induction of high levels
      of antibodies in the immunized group; the antibodies were able to increase
      bacterial phagocytosis by mouse peritoneal cells. The cellular immune response
      was characterized by the production of gamma-interferon, IL-2 and IL-17 by
      splenocytes and nitric oxide by peritoneal cells of immunized mice, upon
      stimulation with rPotD. Taken together our results suggest that PotD is a
      promising candidate to be included in a protein based pneumococcal vaccine, able
      to induce phagocytic antibodies, a Th1 cellular immune response and production of
      IL-17, reducing nasopharyngeal colonization, the main event responsible for
      transmission of pneumococci in humans.

PMID- 27884475
TI  - Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in
      Communities (ARIC) Study.
AB  - BACKGROUND: Frail individuals are at increased risk for poor outcomes, including
      adverse drug events. Kidney function is often compromised in frailty and is a key
      consideration in medication choice and dosing; however, creatinine-based measures
      of kidney function may be biased in frail individuals. STUDY DESIGN:
      Observational study. SETTING & PARTICIPANTS: 4,987 community-dwelling older men
      and women with complete data who participated in visit 5 of the Atherosclerosis
      Risk in Communities (ARIC) Study (2011-2013). PREDICTORS: Kidney measures
      included glomerular filtration rate (GFR) estimated using serum creatinine
      (eGFRcr) and serum cystatin C level (eGFRcys) and urine albumin-creatinine ratio.
      OUTCOME: Frailty, defined using established criteria of 3 or more frailty
      characteristics (weight loss, slowness, exhaustion, weakness, and low physical
      activity). RESULTS: 341 (7%) participants were classified as frail, 1,475 (30%)
      had eGFRcr<60mL/min/1.73m2, 2,480 (50%) had eGFRcys<60mL/min/1.73m2, and 1,006
      (20%) had albuminuria with albumin excretion >= 30mg/g. Among frail participants,
      prevalences of eGFRcr and eGFRcys<60mL/min/1.73m2 were 45% and 77%, respectively.
      Adjusted for covariates, frailty showed a moderate association with eGFRcr and a
      strong association with eGFRcys and albumin-creatinine ratio. Frail individuals
      with eGFRcr of 60 to <75mL/min/1.73m2 were frequently reclassified to lower eGFR
      categories using eGFRcys (49% to 45-<60, 32% to 30-<45, and 3% to
      <30mL/min/1.73m2). Hyperpolypharmacy (taking >=10 classes of medications) was
      more common in frail individuals (54% vs 38% of nonfrail), including classes
      requiring kidney clearance (eg, digoxin) and associated with falls and subsequent
      complications (eg, hypnotic/sedatives and anticoagulants). LIMITATIONS: Cross
      sectional study design. CONCLUSIONS: Frail individuals had a high prevalence of
      reduced kidney function, with large discrepancies when reduced kidney function
      was classified by eGFRcys versus eGFRcr. Given the substantial medication burden
      and uncertainty in chronic kidney disease classification, confirmation of kidney
      function with alternative biomarkers may be warranted to ensure careful
      prescribing practices in this vulnerable population.

PMID- 27884477
TI  - Map of different vaccine supply chain efficiency measures.

PMID- 27884478
TI  - Vaccine provision: Delivering sustained & widespread use.
AB  - The administration of a vaccine to a recipient is the final step in a development
      and production process that may have begun several decades earlier. Here we
      describe the scale and complexity of the processes that brings a candidate
      vaccine through clinical development to the recipient. These challenges include
      ensuring vaccine quality (between 100 and 500 different Quality Control tests are
      performed during production to continually assess safety, potency and purity);
      making decisions about optimal vaccine presentation (pre-filled syringes versus
      multi-dose vials) that affect capacity and supply; and the importance of
      maintaining the vaccine cold chain (most vaccines have stringent storage
      temperature requirements necessary to maintain activity and potency). The
      ultimate aim is to make sure that an immunogenic product matching the required
      specifications reaches the recipient. The process from concept to licensure takes
      10-30years. Vaccine licensure is based on a file submitted to regulatory agencies
      which contains the comprehensive compilation of chemistry, manufacturing
      information, assay procedures, preclinical and clinical trial results, and
      proposals for post-licensure effectiveness and safety data collection. Expedited
      development and licensure pathways may be sought in emergency settings: e.g., the
      2009 H1N1 influenza pandemic, the 2014 West African Ebola outbreak and
      meningococcal serogroup B meningitis outbreaks in the United States and New
      Zealand. Vaccines vary in the complexity of their manufacturing process.
      Influenza vaccines are particularly challenging to produce and delays in
      manufacturing may occur, leading to vaccine shortages during the influenza
      season. Shortages can be difficult to resolve due to long manufacturing lead
      times and stringent, but variable, local regulations. New technologies are
      driving the development of new vaccines with simplified manufacturing
      requirements and with quality specifications that can be confirmed with fewer
      tests. These technologies could have far-reaching effects on supply, cost of
      goods, and on response timing to a medical need until product availability.

PMID- 27884479
TI  - A pilot training program for people in recovery of mental illness as vocational
      peer support workers in Hong Kong - Job Buddies Training Program (JBTP): A
      preliminary finding.
AB  - OBJECTIVES: The present study reviews the delivery of a pilot curriculum
      mentorship-based peer vocational support workers training in a Hong Kong public
      psychiatric hospital. The present paper reports (1) on the development of a peer
      vocational support workers training - Job Buddies Training Program (JBTP) in Hong
      Kong; and (2) preliminary findings from both quantitative and qualitative
      perspectives. METHOD: The curriculum consists of 15-session coursework, 8-session
      storytelling workshop and 50-hour practicum to provide Supported Employment Peer
      Service (SEPS) under the mentorship of occupational therapists. Six trainees were
      assessed using three psychosocial assessments and qualitative methods. FINDINGS:
      Compared to the baseline, the Job Buddies (JB) trainees showed an increase in
      awareness of their own recovery progress, occupational competence and problem
      solving skills at the end of the training. Their perceived level of self-stigma
      was also lessened. In post-training evaluation, all Job Buddies trainees said
      they perceived positive personal growth and discovered their own strengths. They
      also appreciated the help from their mentors and gained mutual support from other
      trainees and from exposure with various mini-projects in the training.
      CONCLUSIONS AND IMPLICATIONS: This pilot study provides an example of
      incorporating peer support and manualized training into existing work
      rehabilitation service for our JB trainees. Further studies on the effectiveness
      of service provided by peer support workers and for development on the potential
      use of peer support workers in other clinical and rehabilitation settings with
      larger subjects will be fruitful.

PMID- 27884480
TI  - Subcutaneous emphysema after vigorous sneezing in the setting of acute frontal
      sinusitis.
AB  - INTRODUCTION: Subcutaneous emphysema [SCE] can develop due to traumatic,
      infectious, and spontaneous causes and usually localizes to the periorbital
      space. CASE: We present a case of an 18-year-old male with an 8-day history of
      migraine-like headaches followed by the acute onset of frontofacial swelling
      after vigorous sneezing. Radiologic and physical exam findings supported a
      diagnosis of frontofacial SCE in the setting of frontal sinusitis. DISCUSSION: A
      sneeze, although usually benign, causes a significant increase in intranasal
      pressure. When coupled with a history significant for facial trauma or
      rhinosinusitis, this rise in pressure can be sufficient to cause fracturing of
      the bone overlying a paranasal sinus, leading to the formation of SCE.

PMID- 27884481
TI  - At What Age Does Stroke Risk Increase in Patients With Atrial Fibrillation? Does
      It Depend on Where You Live?

PMID- 27884482
TI  - The Sum of Its Parts: The Polygenic Basis of Coronary Artery Disease.

PMID- 27884483
TI  - Erratum.

PMID- 27884484
TI  - Ross, Hybrid Arch, and Frozen Elephant Trunk Reconstruction for Late
      Complications of Bicuspid Aortic Valve and Aortopathy.
AB  - Young patients with bicuspid aortic valve disease and aortopathy remain a
      clinical challenge, with many requiring multiple corrective operations throughout
      their lifetimes. Innovative surgical approaches are often required to address
      complex aortic pathologic conditions but leave patients at risk for
      reintervention, lifelong anticoagulation, and suboptimal hemodynamics. We
      describe an active 44-year-old female triathlete with recurrent bicuspid aortic
      stenosis, a small aortic root, a hypoplastic aortic arch and complex distal arch,
      and a descending aortic aneurysm, who underwent a single-stage reconstruction
      with a combined Ross procedure, hybrid arch, and frozen elephant trunk
      reconstruction.

PMID- 27884485
TI  - The Anthropocene Biosphere: Supporting 'Open Interdisciplinarity' through
      Blogging.
AB  - This paper describes a process of 'open' interdisciplinary scholarship.
      Researchers from across the University of Oklahoma blogged about a recent paper
      by ecologist Erle Ellis, and met in person to discuss posts. They then hosted
      Ellis for a seminar on questions that emerged, and for a public panel discussion.

PMID- 27884487
TI  - Hair ethyl glucuronide concentrations in teetotalers: Should we re-evaluate the
      lower cut-off?
AB  - AIMS: Ethyl glucuronide in hair (hEtG) can be used to assess the retrospective
      consumption of alcohol. A lower cut-off of 7pg/mg hair in the 0-3cm proximal
      scalp hair segment has been used for repeated alcohol consumption in the previous
      three months. While a concentration below this cut-off is stated not to
      contradict self reported abstinence, it is often used to assess whether an
      individual has remained abstinent in the period prior to hair sampling. Here, we
      address hEtG concentrations in alcohol consuming individuals and critically
      evaluate this cut-off value. METHODS: Ten individuals remained abstinent from
      alcohol for 12 weeks. A lock of hair was cut before the start of the study, and
      the regrown hairs were cut after twelve weeks of abstinence. Hair EtG
      concentrations were measured both at baseline and after 12 weeks of abstinence.
      Study compliance was assessed by urine analysis every 2-3 days by liquid
      chromatography-tandem mass spectrometry with a lower limit of quantification
      (LLOQ) of 0.1MUg/mL. HEtG concentrations were assessed in the first 3cm hair
      using gas chromatography-tandem mass spectrometry with an LLOQ of 0.2pg/mg.
      RESULTS: At the beginning of the study, participants had hEtG concentrations
      ranging between <LLOQ and 14.0pg/mg hair, matching their pre-study reported
      alcohol consumption (between 0 to 85g alcohol consumed per week). After 12 weeks
      of abstinence, only one participant had an hEtG concentration below the LLOQ.
      Other participants had hEtG concentrations between 0.2 and 4.5pg/mg hair. All
      urine results were below LLOQ, providing evidence for complete abstinence during
      the study. DISCUSSION: In participants consuming no alcohol, all but one had low,
      but measurable hEtG concentrations (up to 4.5pg/mg hair), which was in the
      participant with the highest pre-study alcohol consumption. As only regrown hairs
      were cut, it is not likely that this was due to residual EtG from the pre-study
      period. CONCLUSIONS: Although the number of specimens was low, this study reports
      measurable hEtG concentrations following total abstinence, although not exceeding
      the current 7pg/mg cut-off for hair. A suitable sensitive method (GC-MS/MS) is
      preferred when assessing alcohol abstinence. We propose that the current cut-off
      of 7pg/mg should be discussed further, and, in view of the small study sample,
      evaluated using a larger sample size.

PMID- 27884486
TI  - Epidemiologic analysis: Prophylaxis and multidrug-resistance in surgery.
AB  - BACKGROUND: Surgical site infection is defined as an infection related to the
      surgical procedure in the area of manipulation occurring within the first 30
      postoperative days. The diagnostic criteria include: purulent drainage, isolation
      of microorganisms, and signs of infection. AIMS: To describe the epidemiologic
      characteristics and differences among the types of prophylactic regimens
      associated with hospital-acquired infections at the general surgery service of a
      tertiary care hospital. MATERIAL AND METHODS: The electronic case records of
      patients that underwent general surgery at a tertiary care hospital within the
      time frame of January 1, 2013 and December 31, 2014 were reviewed. A convenience
      sample of 728 patients was established and divided into the following groups:
      Group 1: n=728 for the epidemiologic study; Group 2: n=638 for the evaluation of
      antimicrobial prophylaxis; and Group 3: n=50 for the evaluation of multidrug
      resistant bacterial strains in the intensive care unit. The statistical analysis
      was carried out with the SPSS 19 program, using the Mann-Whitney U test and the
      chi-square test. RESULTS: A total of 728 procedures were performed (65.9% were
      elective surgeries). Three hundred twelve of the patients were males and 416 were
      females. Only 3.98% of the patients complied with the recommended antimicrobial
      prophylaxis, and multidrug-resistant bacterial strains were found in the
      intensive care unit. DISCUSSION: A single prophylactic dose is effective, but
      adherence to this recommendation was not adequate. CONCLUSIONS: The prophylactic
      guidelines are not strictly adhered to in our environment. There was a
      significant association between the development of nosocomial infections from
      multidrug-resistant germs and admission to the intensive care unit.

PMID- 27884488
TI  - Untied horizontal mattress and wound glue to reduce scarring in simple paediatric
      wounds.

PMID- 27884489
TI  - Geochemical speciation, bioavailability and source identification of selected
      metals in surface sediments of the Southern Caspian Sea.
AB  - Geochemical speciation of As, Cd, Co, Cr, Cu, Ni, Pb, V and Zn were determined in
      the surface sediments of the southern Caspian Sea. A five-step sequential
      extraction technique was used to determine the chemical forms of metals. Mean
      concentrations (ppm) of heavy metals were (mean+/-S.D.) As: 9.94+/-1.71, Cd:
      0.87+/-0.23, Co: 14.85+/-2.80, Cr: 72.29+/-19.48, Cu: 18.91+/-4.48, Ni: 32.87+/
      5.25, Pb: 12.48+/-3.22, V: 86.07+/-20.71 and Zn: 66.85+/-10.11. Among the metals,
      Cu, As, Pb and Zn exhibited relatively higher mobility, while Cd, Co, Cr, Ni and
      V were found mainly in the residual fractions. Cu and As showed the highest
      percentages in the exchangeable phase while Co and Cr had the lowest percentages
      in the phase. The Risk Assessment Code (RAC) values indicated that As, Cu and V
      had medium risk at some sampling sites. According to pollution load index (PLI),
      sediments from some sampling sites were polluted.

PMID- 27884490
TI  - Letter to the editor regarding: Stuck in the middle? A perspective on ongoing pro
      competitive reforms in Dutch mental health care.

PMID- 27884491
TI  - Impact of patient outcomes and cost aspects on reimbursement recommendations in
      Poland in 2012-2014.
AB  - The aim of this study was to assess the influence of different factors on the
      final reimbursement recommendations for drugs in Poland and to identify the
      correlation between these factors and the probability of a positive reimbursement
      recommendation for an applicant drug issued by the President of the Agency for
      Health Technology Assessment and Tariff System (AOTMiT). We analysed all
      recommendations for the period of 2012-2014 in Poland, three years following the
      launch of the new Reimbursement Act of Medicines, Foodstuffs Intended for
      Particular Nutritional Uses and Medical Devices. For each recommendation we
      collected data on efficacy, safety, cost of therapy, cost-effectiveness, quality
      of evidence, orphan drug status and others. Logistic regression was used to
      identify factors that increase the odds of a positive reimbursement
      recommendation. We analysed 221 recommendations for drugs, of which 78% were
      positive. We observed significant associations of all selected factors with
      positive recommendations. Proven efficacy and safety were associated with much
      greater odds for a positive reimbursement recommendation (123.5 and 42.6,
      respectively) than cost factors, which may suggest that patient outcome is much
      more important than the results of the cost-effectiveness analysis (odds ratio of
      3.5) and the general cost of therapy (odds ratio of 3) in the analysed period.

PMID- 27884492
TI  - What women want: Exploring pregnant women's preferences for alternative models of
      maternity care.
AB  - Depending on obstetric risk, maternity care may be provided in one of two
      locations at hospital level: a consultant-led unit (CLU) or a midwifery-led unit
      (MLU). Care in a MLU is sparsely provided in Ireland, comprising as few as two
      units out of a total 21 maternity units. Given its potential for greater
      efficiencies of care and cost-savings for the state, there has been an increased
      interest to expand MLUs in Ireland. Yet, very little is known about women's
      preferences for midwifery-led care, and whether they would utilise this service
      when presented with the choice of delivering in a CLU or MLU. This study seeks to
      involve women in the future planning of maternity care by investigating their
      preferences for care and subsequent motivations when choosing place of birth.
      Qualitative research is undertaken to explore maternal preferences for these
      different models of care. Women only revealed a preference for the MLU when co
      located with a CLU due to its close proximity to medical services. However, the
      results suggest women do not have a clear preference for either model of care,
      but rather a hybrid model of care which encompasses features of both consultant-
      and midwifery-led care.

PMID- 27884495
TI  - A homogenization model of the Voigt type for skeletal muscle.
AB  - A three-dimensional constitutive model for skeletal muscle incorporating
      microstructural characteristics is developed and numerically implemented in a
      general purpose finite element program. The proposed model takes into account
      explicitly the volume fractions of muscle fibers and connective tissue by using
      the Voigt homogenization approach to bridge the different length scales of the
      muscle structure. The model is used to estimate the active and passive
      homogenized muscle response. Next, the model is validated by experimental data
      and periodic three-dimensional unit cell calculations comprising various fiber
      volume fractions and mechanical properties of the constituents. The model is
      found to be in very good agreement with both the experimental data and the finite
      element results for all the examined cases. The influence of fiber volume
      fraction and material properties of constituents on effective muscle response
      under several loading conditions is examined.

PMID- 27884494
TI  - Consensus conference on TIPS management: Techniques, indications,
      contraindications.
AB  - The trans jugular intrahepatic Porto systemic shunt (TIPS) is no longer viewed as
      a salvage therapy or a bridge to liver transplantation and is currently indicated
      for a number of conditions related to portal hypertension with positive results
      in survival. Moreover, the availability of self-expandable
      polytetrafluoroethylene (PTFE)-covered endoprostheses has dramatically improved
      the long-term patency of TIPS. However, since the last updated International
      guidelines have been published (year 2009) new evidence have come, which have
      open the field to new indications and solved areas of uncertainty. On this basis,
      the Italian Association of the Study of the Liver (AISF), the Italian College of
      Interventional Radiology-Italian Society of Medical Radiology (ICIR-SIRM), and
      the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI)
      promoted a Consensus Conference on TIPS. Under the auspices of the three
      scientific societies, the consensus process started with the review of the
      literature by a scientific board of experts and ended with a formal consensus
      meeting in Bergamo on June 4th and 5th, 2015. The final statements presented here
      were graded according to quality of evidence and strength of recommendations and
      were approved by an independent jury. By highlighting strengths and weaknesses of
      current indications to TIPS, the recommendations of AISF-ICIR-SIRM-SIAARTI may
      represent the starting point for further studies.

PMID- 27884493
TI  - Initial genetic dissection of serum neuroactive steroids following chronic
      intermittent ethanol across BXD mouse strains.
AB  - Neuroactive steroids modulate alcohol's impact on brain function and behavior.
      Ethanol exposure alters neuroactive steroid levels in rats, humans, and some
      mouse strains. We conducted an exploratory analysis of the neuroactive steroids
      (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP), (3alpha,5alpha)-3,21
      dihydroxypregnan-20-one (3alpha,5alpha-THDOC), and pregnenolone across 126-158
      individuals and 19 fully inbred strains belonging to the BXD family, which were
      subjected to air exposure, or chronic intermittent ethanol (CIE) exposure.
      Neuroactive steroids were measured by gas chromatography-mass spectrometry in
      serum following five cycles of CIE or air exposure (CTL). Pregnenolone levels in
      CTLs range from 272 to 578 pg/mL (strain variation of 2.1 fold with p = 0.049 for
      strain main effect), with heritability of 0.20 +/- 0.006 (SEM), whereas in CIE
      cases values range from 304 to 919 pg/mL (3.0-fold variation, p = 0.007), with
      heritability of 0.23 +/- 0.005. 3alpha,5alpha-THP levels in CTLs range from 375
      to 1055 pg/mL (2.8-fold variation, p = 0.0007), with heritability of 0.28 +/-
      0.01; in CIE cases they range from 460 to 1022 pg/mL (2.2-fold variation, p =
      0.004), with heritability of 0.23 +/- 0.005. 3alpha,5alpha-THDOC levels in CTLs
      range from 94 to 448 pg/mL (4.8-fold variation, p = 0.002), with heritability of
      0.30 +/- 0.01, whereas levels in CIE cases do not differ significantly. However,
      global averages across all BXD strains do not differ between CTL and CIE for any
      of the steroids. 3alpha,5alpha-THDOC levels were lower in females than males in
      both groups (CTL -53%, CIE -55%, p < 0.001). Suggestive quantitative trait loci
      are identified for pregnenolone and 3alpha,5alpha-THP levels. Genetic variation
      in 3alpha,5alpha-THP was not correlated with two-bottle choice ethanol
      consumption in CTL or CIE-exposed animals. However, individual variation in
      3alpha,5alpha-THP correlated negatively with ethanol consumption in both groups.
      Moreover, strain variation in neuroactive steroid levels correlated with numerous
      behavioral phenotypes of anxiety sensitivity accessed in GeneNetwork, consistent
      with evidence that neuroactive steroids modulate anxiety-like behavior.

PMID- 27884496
TI  - Glucagon like peptide-1 and its receptor agonists: Their roles in management of
      Type 2 diabetes mellitus.
AB  - This study summarizes major work which investigated the roles of glucagon like
      peptide-1 (GLP-1) and its receptor (GLP-1R); the use of GLP-1-R agonists and
      dipeptidyl peptidase 4 inhibitor in the management of type 2 diabetes mellitus.
      It focuses on the recent therapeutic development which has occurred in this
      field, and also discusses the potential treatments which can be discovered and
      implemented in the near future to design an effective therapy for type 2 diabetes
      mellitus.

PMID- 27884497
TI  - Effect of rotator cuff strengthening as an adjunct to standard care in subjects
      with adhesive capsulitis: A randomized controlled trial.
AB  - STUDY DESIGN: Randomized controlled trial. PURPOSE OF THE STUDY: To study the
      effect of adding rotator cuff (RC) muscles strengthening to joint mobilization
      and transcutaneous electrical nerve stimulation (TENS) in patients with adhesive
      capsulitis. METHODS: A prospective, parallel-group, randomised clinical trial was
      conducted on 42 patients. One group received TENS and joint mobilization and in
      the other group RC muscles strengthening was added. Treatment was given for 12
      sessions within 4 weeks. RESULTS: When compared between the groups statistically
      significant changes were seen in all the outcome measures in the group that
      received RC muscle strengthening exercises vs TENS and mobilization. VAS 12.76 +/
      1.04 vs 4.05 +/- 1.32; SPADI 34.66 +/- 6.69 vs 54.29 +/- 12.17; PFPS 3.06 +/-
      0.80 vs 4.70 +/- 0.81; and ROM (elevation >125 vs >110 degrees and rotations >70
      vs >48 degrees). CONCLUSIONS: Addition of a structured RC strengthening program
      to TENS and joint mobilization in the treatment of adhesive capsulitis resulted
      in improvement in pain, ROM and function. LEVEL OF EVIDENCE: 1b.

PMID- 27884498
TI  - Early Sexual Debut and Associated Risk Behaviors Among Sexual Minority Youth.
AB  - INTRODUCTION: Early sexual debut, sexual risk taking, substance use, violent
      victimization, and suicidal behaviors are more prevalent among sexual minority
      than sexual nonminority youth. Although associations between early sexual debut
      and these risk behaviors exist, little is known about such associations among
      sexual minority youth. This study examined these associations among sexual
      minority U.S. high school students and their sexual nonminority peers. METHODS:
      In 2015, the national Youth Risk Behavior Survey included questions assessing
      sexual orientation for the first time. In 2016, data from this nationally
      representative sample of 15,624 U.S. high school students were analyzed to
      determine if associations between early sexual debut and other health risk
      behaviors varied by sexual orientation, by calculating adjusted (for sex,
      race/ethnicity, and age) prevalence ratios (APRs). RESULTS: Associations between
      early sexual debut and other health risk behaviors did not vary significantly by
      sexual orientation. Early sexual debut (first sexual intercourse before age 13
      years) was associated with sexual risk taking, substance use, violent
      victimization, and suicidal thoughts/attempts among students identifying as
      lesbian, gay, or bisexual (LGB) and among students identifying as heterosexual,
      for example, being currently sexually active (LGB students: APR=1.82, 95%
      CI=1.35, 2.45; heterosexual students: APR=2.50, 95% CI=2.22, 2.81) and not using
      a condom at last sexual intercourse (LGB students: APR=1.50, 95% CI=1.18, 1.91;
      heterosexual students: APR=1.29, 95% CI=1.09, 1.52). CONCLUSIONS: School-based
      sexual health programs might appropriately utilize strategies that are inclusive
      of sexual minority students, encourage delay of sexual intercourse, and
      coordinate with violence and substance use prevention programs.

PMID- 27884500
TI  - Different impact of aspirin on renal progression in patients with predialysis
      advanced chronic kidney disease with or without previous stroke.
AB  - BACKGROUND: The benefit of reducing the risk of stroke against increasing the
      risk of renal progression associated with antiplatelet therapy in patients with
      advanced chronic kidney disease (CKD) is controversial. METHODS: We enrolled 1301
      adult patients with advanced CKD treated with erythropoiesis stimulating agents
      from January 1, 2002 to June 30, 2009 from the 2005 Longitudinal Health Insurance
      Database in Taiwan. All of the patients were followed until the development of
      the primary or secondary endpoints, or the end of the study (December 31, 2011).
      The primary endpoint was the development of ischemic stroke, and the secondary
      endpoints included hospitalization for bleeding events, cardiovascular mortality,
      all-cause mortality, and renal failure. The adjusted cumulative probability of
      events was calculated using multivariate Cox proportional regression analysis.
      RESULTS: Adjusted survival curves showed that the usage of aspirin was not
      associated with ischemic stroke, hospitalization for bleeding events,
      cardiovascular mortality or all-cause mortality, however, it was significantly
      associated with renal failure. In subgroup analysis, aspirin use was associated
      with renal failure in the patients with no history of stroke (HR, 1.41; 95% CI,
      1.14-1.73), and there was a borderline interaction between previous stroke and
      the use of aspirin on renal failure (interaction p=0.0565). CONCLUSIONS: There
      was no significant benefit in preventing ischemic stroke in the patients with
      advanced CKD who received aspirin therapy. Furthermore, the use of aspirin was
      associated with the risk of renal failure in the patients with advanced CKD
      without previous stroke.

PMID- 27884499
TI  - Comparison of three types of exercise in the treatment of rotator cuff
      tendinopathy/shoulder impingement syndrome: A randomized controlled trial.
AB  - OBJECTIVES: To assess the efficacy of three different exercise programmes in
      treating rotator cuff tendinopathy/shoulder impingement syndrome. DESIGN:
      Parallel group randomised clinical trial. SETTING: Two out-patient NHS
      physiotherapy departments in Manchester, United Kingdom. PARTICIPANTS: 120
      patients with shoulder pain of at least three months duration. Pain was
      reproduced on stressing the rotator cuff and participants had full passive range
      of movement at the shoulder. INTERVENTIONS: Three dynamic rotator cuff loading
      programmes; open chain resisted band exercises (OC) closed chain exercises (CC)
      and minimally loaded range of movement exercises (ROM). MAIN OUTCOMES: Change in
      Shoulder Pain and Disability Index (SPADI) score and the proportion of patients
      making a Minimally Clinically Important Change (MCIC) in symptoms 6 weeks after
      commencing treatment. RESULTS: All three programmes resulted in significant
      decreases in SPADI score, however there were no significant differences between
      the groups. Participants making a MCIC in symptoms were similar across all
      groups, however more participants deteriorated in the ROM group. Dropout rate was
      higher in the CC group, but when only patients completing treatment were
      considered more patients in the CC group made a meaningful reduction in pain and
      disability. CONCLUSIONS: Open chain, closed chain and range of movement exercises
      all seem to be effective in bringing about short term changes in pain and
      disability in patients with rotator cuff tendinopathy. ISRCTN76701121.

PMID- 27884501
TI  - Influence of living environment and subjective economic hardship on new-onset of
      low back pain for survivors of the Great East Japan Earthquake.
AB  - BACKGROUND: The Great East Japan Earthquake and subsequent tsunami devastated the
      northeastern part of Japan. Low back pain is thought to increase after a natural
      disaster and is related to various factors. The aim of this study was to examine
      the influencing factors of "Living environment" and "Subjective economic
      hardship" on new-onset of low back pain in the chronic phase for the survivors of
      the earthquake evaluated by a self-report questionnaire. METHODS: A panel study
      was conducted with the Great East Japan Earthquake survivors at 2 and 3 years
      after the disaster. New-onset of low back pain was defined as low back pain
      absent at the 1st period (2 years after the earthquake) and present at the 2nd
      period (3 years after the earthquake). Living environment was divided into 4
      categories (1. Living in the same house as before the earthquake, 2. Living in a
      prefabricated house, 3. Living in a new house, 4. Others: Living in an apartment,
      house of relatives or acquaintance). Subjective economic hardship was obtained
      using the following self-report question: "How do you feel about the current
      economic situation of your household?" The response alternatives were "Normal",
      "A little bit hard", "Hard", and "Very hard". A univariate and multivariate
      logistic regression models were used. RESULTS: 1357 survivors consented to join
      this study. There was no significant association between new-onset of low back
      pain and living environment. There was significant association between new-onset
      of low back pain and "A little hard" (OR = 1.6, 95% CI = 1.07-2.40), "Hard" (OR =
      2.2, 95% CI = 1.56-3.74), and "Very hard" (OR = 3.19, 95% CI = 1.84-5.53) in
      subjective economic hardship. CONCLUSIONS: Subjective economic hardship was
      significantly associated with new-onset of low back pain in the chronic phase for
      survivors of the Great East Japan Earthquake.

PMID- 27884502
TI  - The role of arterial conduits for revascularisation in adult orthotopic liver
      transplantation.
AB  - The successful outcome in orthotopic liver transplantation (OLT) is critically
      dependent on the uncompromised hepatic graft blood inflow. Arterial conduits
      represent a good solution in cases where conventional revascularisation is not
      possible. The purpose of this systematic review is to analyse the published
      evidence on the use of arterial conduits in adult OLT. After review of the Pubmed
      and EMBASE databases, 19 relevant studies were identified and analysed. Even
      though patient survival was comparable, most large studies reported worse 1-, 3-
      and 5-year graft survival rates compared to grafts with standard arterial
      revascularisation. Primary grafts were more commonly affected than re-grafts.
      Early and late hepatic artery thrombosis occurred more commonly, while the use of
      an arterial conduit was identified as an independent risk factor. The overall
      biliary complications were comparable, however, ischaemic cholangiopathy was
      encountered about 3 times more in patients with arterial conduits and strongly
      correlated with the occurrence of late HAT. In conclusion, the use of arterial
      conduit is a useful option in adult OLT in cases that the conventional
      revascularisation technique cannot be used or results in suboptimal arterial
      inflow. More studies directly addressing issues such as pre-operative evaluation
      regarding the need for arterial conduit, the types of vessels used, positioning
      of the conduit and post-operative management are required.

PMID- 27884503
TI  - Steering between Scylla and Charybdis: Picking out the optimum time of double-J
      stent removal following renal transplantation.

PMID- 27884504
TI  - A critical examination of the definition of 'psychoactive effect' in Australian
      drug legislation.
AB  - As the number of new 'psychoactive substances' detected globally has risen
      exponentially, the policy response of assessing and prohibiting each new
      substance individually has become increasingly unworkable. In an attempt to
      disrupt the availability of new as-yet-unscheduled substances, Ireland (2010),
      Poland (2011), Romania (2012), New Zealand (2013), Australia (2015) and the
      United Kingdom (2016) have enacted generic or blanket ban legislation that
      prohibits all 'psychoactive substances' that are not already regulated or belong
      to exempt categories. How such generic legislation defines 'psychoactive
      substance' is therefore crucial. While there is a growing critical literature
      relating to blanket bans of 'psychoactive substances', the Australian legislation
      is yet to be described or critically analysed. In this commentary, we aim to draw
      the attention of local and international drug policy scholars to Australia's
      newest legislative approach to 'psychoactive substances'. Using the Australian
      experience as a case study, we first describe and trace the origins of this
      generic banning approach, especially focusing on how 'psychoactive effect' came
      to be defined. Then, we critically examine the assumptions underpinning this
      definition and the possibilities silenced by it, drawing on the work of
      poststructuralist and critical scholars. In doing so, we explore and raise a
      series of questions about how this legislation works to stabilise drugs, drug
      harms and drug effects, as well as addiction realities; how the category of
      'psychoactive substances' is produced through this legislation; and some of the
      material-discursive effects which accompany this rendering of the 'problem'. We
      offer this commentary not as a comprehensive discussion of each of these elements
      but rather as a starting-point to promote further discussion and debate within
      the drug policy field. To this end, we conclude with a suggested research agenda
      that may help guide such future work.

PMID- 27884505
TI  - The truly disadvantaged? Midlife outcome dynamics of individuals with experiences
      of out-of-home care.
AB  - Little is known about developmental outcomes in midlife of persons who were
      placed in out-of-home care (OHC) in childhood. Utilizing longitudinal Swedish
      data from a cohort of more than 14,000 individuals who we can follow from birth
      (1953) to the age of 55 (2008), this study examines midlife trajectories of
      social, economic, and health-related disadvantages with a specific focus on the
      complexity, timing, and duration of disadvantage in individuals with and without
      childhood experience of OHC. Roughly half of the OHC alumni did not have
      disadvantaged outcomes in midlife. However, experience of OHC was associated with
      a two-fold risk for various forms of permanent disadvantage, net of confounding
      factors. Implications for research, policy, and practice are discussed.

PMID- 27884506
TI  - Family abduction in a national sample of US children.
AB  - This study examined the prevalence and characteristics of family abduction
      episodes occurring in a nationally representative sample of US children ages 0
      17. It drew on the experiences of 13,052 children and youth from the aggregation
      of three cross-sectional waves (2008, 2011, and 2014) of the National Surveys of
      Children Exposed to Violence. The overall prevalence rate was 4.1% for a lifetime
      and 1.2% for a past year episode. Rates were higher for younger than older
      children. Parents constituted 90% of the abductors with females outnumbering
      males 60% to 40%, although men outnumbered women as perpetrators for certain
      types of abductions. A bit less than half of the episodes (43%) were reported to
      police. The experience of a lifetime family abduction had an independent
      association with traumatic stress symptoms independent of exposure to other kinds
      of victimization including child maltreatment and witnessing family violence.

PMID- 27884507
TI  - Childhood adversity and the risk of substance use and delinquency: The role of
      protective adult relationships.
AB  - Youth involved in the child welfare system experience multiple early adversities
      that can contribute to increased risk of substance use and delinquency. Although
      adverse childhood experiences (ACEs) have been associated with poorer behavioral
      outcomes among youth, less is known about the possible protective factors that
      may influence the relationship between early adversity and risk-taking behavior.
      This study examined whether protective adult relationships moderated the link
      between cumulative ACEs and substance use and delinquency after controlling for
      demographic characteristics in child welfare-involved youth. The sample included
      1054 youth, ages 11-17, from the National Survey of Child and Adolescent Well
      Being II who were in the first wave of data collection. Results showed that
      protective adult relationships moderated the relationship between ACEs and
      substance use, but not for delinquency. Specifically, under lower levels of
      protective adult relationships, cumulative ACEs related to increased substance
      use among youth. Implications for child welfare practices to target youths'
      support systems are discussed.

PMID- 27884508
TI  - Adverse childhood experiences and behavioral problems in middle childhood.
AB  - Children who have been exposed to maltreatment and other adverse childhood
      experiences (ACEs) are at increased risk for various negative adult health
      outcomes, including cancer, liver disease, substance abuse, and depression.
      However, the proximal associations between ACEs and behavioral outcomes during
      the middle childhood years have been understudied. In addition, many of the ACE
      studies contain methodological limitations such as reliance on retrospective
      reports and limited generalizability to populations of lower socioeconomic
      advantage. The current study uses data from the Fragile Families and Child
      Wellbeing Study, a national urban birth cohort, to prospectively assess the
      adverse experiences and subsequent behavior problems of over 3000 children. Eight
      ACE categories to which a child was exposed by age 5 were investigated: childhood
      abuse (emotional and physical), neglect (emotional and physical), and parental
      domestic violence, anxiety or depression, substance abuse, or incarceration.
      Results from bivariate analyses indicated that Black children and children with
      mothers of low education were particularly likely to have been exposed to
      multiple ACE categories. Regression analyses showed that exposure to ACEs is
      strongly associated with externalizing and internalizing behaviors and likelihood
      of ADHD diagnosis in middle childhood. Variation in these associations by
      racial/ethnic, gender, and maternal education subgroups are examined. This study
      provides evidence that children as young as 9 begin to show behavioral problems
      after exposure to early childhood adversities.

PMID- 27884509
TI  - Serious physical violence among Arab-Palestinian adolescents: The role of
      exposure to neighborhood violence, perceived ethnic discrimination, normative
      beliefs, and, parental communication.
AB  - This study adopted a social-ecological perspective to exploring perpetration of
      serious physical violence against others among Arab-Palestinian adolescents. A
      total of 3178 adolescents (aged 13-18) completed anonymous, structured, self
      report questionnaire, which included selected items from several instruments that
      measured variables relating to the constructs examined in the study. We explored
      the association of individual characteristics (age, gender, normative beliefs
      about violence, and perceived ethnic discrimination), familial characteristics
      (parent-adolescent communication and socioeconomic status), and contextual
      characteristics (exposure to community violence in the neighborhood) with
      perpetration of serious physical violence against others. A moderation-mediation
      model was tested, and 28.4% of the adolescents reported that they had perpetrated
      serious physical violence against others at least once during the month preceding
      the study. The findings also show that exposure of youth to violence in their
      neighborhood correlated significantly and positively with their perpetration of
      serious physical violence against others. A similar trend was revealed with
      respect to personal perceptions of ethnic discrimination. These correlations were
      mediated by the adolescents' normative beliefs about violence. Furthermore, the
      correlation of direct exposure to violence in the neighborhood and normative
      beliefs about violence with perpetration of serious physical violence against
      others was stronger among adolescents who have poor communication with their
      parents than among those who have strong parental communication.

PMID- 27884510
TI  - Is selective nodal irradiation in non-small cell lung cancer still safe when
      using IMRT? Results of a prospective cohort study.
AB  - BACKGROUND AND PURPOSE: Isolated nodal failures (INF) are rare after 3D-conformal
      radiotherapy (3D-CRT) for stage III non-small cell lung cancer (NSCLC). Since
      incidental nodal irradiation doses are lower with Intensity Modulated Radiation
      Therapy (IMRT) than with 3D-CRT, INF may be higher after IMRT. We therefore
      investigated the incidence of INF after IMRT in stage III NSCLC patients.
      MATERIALS AND METHODS: Stage III NSCLC patients undergoing radical radiotherapy
      using IMRT in the period January 2010 till March 2012 were included. The primary
      endpoint was the rate of INF, secondary endpoints included patterns of failure,
      progression free survival (PFS), overall survival (OS) and toxicity. RESULTS: 183
      stage III NSCLC patients were enrolled. With a median follow-up of 58.0months
      2.2% of patients had an INF. The median PFS was 15.0months, the median OS
      19.5months. Patterns of recurrence: 2.2% INF, 11.5% local and 2.7% loco-regional
      recurrence, 26.8% distant metastases only, 18.0% a combination of local/loco
      regional and distant metastases, and 38.3% patients without recurrence. One INF
      was out of field, in adjacent lymph nodes. Acute toxicity was limited.
      DISCUSSION: Selective nodal irradiation using IMRT in stage III NSCLC patients
      results in a low in-field incidence of INF (2.2%), similar to 3D-CRT, and may
      thus be considered safe.

PMID- 27884511
TI  - Effects of previous physical training on adriamycin nephropathy and its
      relationship with endothelial lesions and angiogenesis in the renal cortex.
AB  - AIMS: Adriamycin (ADR)-induced nephropathy is one of the most experimental models
      used in progressive kidney disease. A single dose of this drug induces a
      progressive and irreversible proteinuria that progresses to focal segmental
      glomerulosclerosis and tubulointerstitial lesions. Regular physical activity has
      been considered as a therapeutic intervention in several diseases. This study
      evaluated the influence of previous physical training in renal damage induced by
      ADR and the role of endothelial lesions and angiogenesis in this process. MAIN
      METHODS: Male Wistar rats were subjected or not to treadmill running for 4weeks
      and then injected with ADR (2.5mg/kg, i.v.) or saline. Twenty-four-hour urine
      samples were collected for albuminuria measurement, and blood samples were
      collected to measure plasma creatinine 60days after the injections. The kidneys
      were removed for histological, immunohistochemical, Western blot and ELISA
      studies. KEY FINDINGS: ADR-treated rats presented increases in plasma creatinine
      levels, albuminuria, podocyte damage, and enlargement of the tubular interstitial
      relative area, as well as higher macrophage numbers in the renal cortex,
      interleukin (IL)-1beta levels in renal tissue and urinary monocyte
      chemoattractant protein (MCP)-1, which were associated with reduction in vascular
      endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS)
      expressions and peritubular capillary (PTC) density in renal cortex. These
      alterations were less intense in the animals subjected to previous exercise
      training. SIGNIFICANCE: Physical training prior to ADR injection reduced the
      renal damage induced by this drug. This effect was related to angiogenesis and
      reduction in the endothelial lesions and inflammatory process in the renal cortex
      of these animals.

PMID- 27884512
TI  - Design, synthesis and antithrombotic evaluation of novel non-peptide thrombin
      inhibitors.
AB  - Ten derivatives of 4-((1,2,3,4-tetrahydrobenzo[4,5]imidazo[1,2-a]pyrazin-1
      yl)methyl)benzimida-mide (I-1~I-2, II-1~II-8) were designed, synthesized and
      evaluated for their inhibitory effect on human thrombin. Compound II-7
      (IC50=82.8nM), which showed the strongest thrombin inhibitory activity among the
      tested compounds, was chosen as the lead compound, and ten carbamate derivatives
      (II-9a~II-13a, II-9b~II-12b, II-14) were prepared and evaluated for their
      anticoagulant activity. The results indicate that most of the tested compounds
      exhibit a certain degree of inhibitory effect on thrombin-induced platelet
      aggregation, among which compounds II-11a (IC50=8.16MUM) and II-14 (IC50=1.95MUM)
      show better anti-platelet aggregation activity than the others. The in vivo
      experimental results in rat venous thrombosis model also demonstrate compounds II
      11a and II-14 can significantly reduce thrombosis in a dose-response manner. It
      is worth pointing out that the enhanced potency of compound II-14 may be the
      synergetic effect of 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) and II-7
      which are generated by hydrolysis in vivo.

PMID- 27884513
TI  - Biotransformation of rutabaga phytoalexins by the fungus Alternaria brassicicola:
      Unveiling the first hybrid metabolite derived from a phytoalexin and a fungal
      polyketide.
AB  - The biotransformations of the rutabaga phytoalexins rutalexin, brassicanate A,
      isalexin and rapalexin A by the plant pathogenic fungus Alternaria brassicicola
      are reported. While the biotransformations of rutalexin, brassicanate A, and
      isalexin are fast, rapalexin A is resistant to fungal transformation.
      Unexpectedly, biotransformation of rutalexin yields a hybrid metabolite named
      rutapyrone, derived from rutalexin metabolism and phomapyrone G, a fungal
      metabolite produced by A. brassicicola. These fungal transformations are
      detoxification reactions likely carried out by different enzymes. The discovery
      of rapalexin A resistance to detoxification suggests that this phytoalexin in
      combination with additional phytoalexins could protect crucifers against this
      pathogen. Phytoalexins resistant to degradation by A. brassicicola are expected
      to provide the producing plants with higher disease resistance levels.

PMID- 27884514
TI  - Less radical surgery for early-stage cervical cancer: Can conization specimens
      help identify patients at low risk for parametrial involvement?
AB  - OBJECTIVE: Radical hysterectomy for cervical cancer is associated with increased
      morbidity over an extrafascial hysterectomy. The goal of this study was to
      determine incidence of and risk factors for parametrial involvement (PI) based on
      conization specimen (CS) and to potentially identify candidates for less radical
      surgery. METHODS: Patients with FIGO IA2-IIA cervical cancer treated with radical
      hysterectomy and pelvic lymph node dissection (RH) from 2000 to 2010 were
      retrospectively identified. Data was extracted from operative and pathology
      reports. Statistical analyses were performed using Fisher's exact test, t-test,
      and asymptotic logistic regression. RESULTS: Of 267 RH patients identified, 118
      (44%) had conization prior to RH. The incidence of PI was 15.7% overall and 7.5%
      in patients treated with conization prior to RH. There was no association between
      PI and histology, stage, grade, or tumor size. Conization patients with PI were
      more likely to have LVSI on CS (77.8% vs. 29.4%) and positive lymph nodes (LNP)
      (66.7% vs. 8.3%). Of patients with positive endocervical curettage, a modest 12%
      had PI, which was not statistically significant. Tumor size, depth of invasion,
      and margin status on CS were not statistically associated with PI. In logistic
      regression analysis, LNP alone or LNP+LVSI were predictive of PI. CONCLUSIONS:
      The incidence of PI in early-stage cervical cancer is significant. Only LVSI on
      CS and LNP were predictors of PI in the current study. While there may be select
      patients with early stage cervical cancer who can be spared parametrectomy,
      additional research is warranted.

PMID- 27884515
TI  - Corrigendum to 'Diagnostic performance and establishment of reference limits of
      HE4 in Korean healthy women' [Gynecol. Oncol. 143 (2016) 128-134].

PMID- 27884516
TI  - Bioleaching combined brine leaching of heavy metals from lead-zinc mine tailings:
      Transformations during the leaching process.
AB  - During the process of bioleaching, lead (Pb) recovery is low. This low recovery
      is caused by a problem with the bioleaching technique. This research investigated
      the bioleaching combination of bioleaching with brine leaching to remove heavy
      metals from lead-zinc mine tailings. The impact of different parameters were
      studied, including the effects of initial pH (1.5-3.0) and solid concentration (5
      20%) for bioleaching, and the effects of sodium chloride (NaCl) concentration (10
      200 g/L) and temperature (25 and 50  degrees C) for brine leaching. Complementary
      characterization experiments (Sequential extraction, X-ray diffractometer (XRD),
      scanning electronic microscope (SEM)) were also conducted to explore the
      transformation of tailings during the leaching process. The results showed that
      bioleaching efficiency was significantly influenced by initial pH and solid
      concentration. Approximately 85.45% of iron (Fe), 4.12% of Pb, and 97.85% of zinc
      (Zn) were recovered through bioleaching in optimum conditions. Increasing the
      brine concentration and temperature promoted lead recovery. Lead was recovered
      from the bioleaching residues at a rate of 94.70% at 25  degrees C and at a rate
      of 99.46% at 50  degrees C when the NaCl concentration was 150 g/L. The study
      showed that bioleaching significantly changed the speciation of heavy metals and
      the formation and surface morphology of tailings. The metals were mainly bound in
      stable fractions after bioleaching.

PMID- 27884517
TI  - Endoscopic morphologic features of ulcerative colitis-associated dysplasia
      classified according to the SCENIC consensus statement.
AB  - BACKGROUND AND AIMS: Recent advances in endoscopic equipment and diagnostic
      techniques have made possible the detection of early dysplasia in the inflamed
      mucosa of ulcerative colitis (UC). The SCENIC consensus statement recommends the
      use of unified terminology for the morphology of dysplasia. In this study, we
      investigated the endoscopic features of high-grade dysplasia (HGD) in a clinical
      setting. METHODS: We retrospectively identified 62 patients with UC who were
      diagnosed with colitis-associated cancer or HGD between 1997 and 2015. A total of
      39 lesions of HGD detected by targeted biopsy sampling in 31 patients were
      reviewed, and the endoscopic morphology was classified according to the SCENIC
      guidelines. RESULTS: In total, 0 (0%), 6 (15.4%), 19 (48.7%), 12 (30.8%), and 2
      (5.1%) lesions with HGD were classified as pedunculated, sessile, superficial
      elevated, flat, and depressed, respectively. Nearly 80% of the lesions were
      located in the rectum or sigmoid colon. All flat and depressed lesions were red
      in color. Typically, sessile/superficial elevated lesions accompanied a flat area
      (Is+IIb/IIa+IIb). Ulceration was observed in 2 depressed lesions (5.1%). Although
      the borders were indistinct in 21 lesions (53.8%) without the use of magnifying
      colonoscopy, all lesions could be distinguished from the surrounding mucosa using
      magnifying endoscopy. CONCLUSIONS: This is the first study to classify the
      morphologic features of HGD using the SCENIC guidelines in a clinical setting.
      Based on our findings, endoscopists should recognize that HGD is frequently
      associated with a flat/superficial elevated area and red discoloration and should
      inspect particularly carefully in the rectum and sigmoid colon. The findings of
      chromoendoscopy and magnifying colonoscopy may also be useful in distinguishing
      lesions from the surrounding mucosa.

PMID- 27884518
TI  - Multitarget stool DNA test: clinical performance and impact on yield and quality
      of colonoscopy for colorectal cancer screening.
AB  - BACKGROUND AND AIMS: Multitarget stool DNA (MT-sDNA) testing is now approved by
      the U.S. Food and Drug Administration for average-risk colorectal cancer
      screening. Trials leading to its approval used blinded colonoscopy as the
      reference standard. In the postapproval screen setting, the clinical performance
      and impact of MT-sDNA testing on unblinded colonoscopy has not been described. We
      measured the impact that knowledge of a positive MT-sDNA test result has on
      colonoscopy yield and quality. METHODS: The unblinded group comprised all
      patients with positive MT-sDNA results on screening from September 1, 2014 to
      September 30, 2015 at a single tertiary center. Off-label test patients were
      excluded. The blinded group included all MT-sDNA-positive participants in a
      preapproval screening study from the same center. Detailed colonoscopy findings
      and withdrawal times were recorded. RESULTS: There were 172 MT-sDNA-positive
      patients in the unblinded group and 72 in the blinded group. More total
      adenomatous/sessile serrated polyps (70% vs 53%, P = .013) and advanced neoplasms
      (28% vs 21%, P = .27) were detected in unblinded than in blinded groups. Median
      numbers of polyps detected were 2 (IQR, 1-4) and 1 (IQR, 0-2) in unblinded and
      blinded groups, respectively (P = .0007). Among polyps detected, flat or slightly
      raised lesions in the right side of the colon were proportionately more frequent
      with unblinded (40%) than with blinded examinations (9%) (P = .0017). Median
      withdrawal time was 19 minutes (IQR, 13-29) in the unblinded group compared with
      13 minutes (IQR, 10-20) in the blinded group (P = .0001). CONCLUSIONS: Knowledge
      of a positive MT-sDNA result appears to have a beneficial impact on the
      diagnostic yield and quality of subsequent colonoscopy.

PMID- 27884519
TI  - Production and characterization of genetically modified human IL-11 variants.
AB  - Interleukin-11 (IL-11) has been expected as a drug on severe thrombocytopenia
      caused by myelo-suppressive chemotherapy. Whereas, development of IL-11 inhibitor
      is also expected for a treatment against IL-11 related cancer progression. Here,
      we will demonstrate the creation of various kinds of genetically modified hIL
      11s. Modified vectors were constructed by introducing N- or O-glycosylation site
      on the region of hIL-11 that does not belong to the core alpha-helical motif
      based on the predicted secondary structure. N-terminal (N: between 22 to 23 aa),
      the first loop (M1:70 to 71 aa), the second loop (M2:114-115 aa), the third loop
      (M3:160-161 aa) and C-terminal (C: 200- aa) were selected for modification. A
      large scale production system was established and the characteristics of modified
      hIL-11s were evaluated. The structure was analyzed by amino acid sequence and
      composition analysis and CD-spectra. Glycan was assessed by monosaccharide
      composition analysis. Growth promoting activity and biological stability were
      analyzed by proliferation of T1165 cells. N-terminal modified proteins were well
      glycosylated and produced. Growth activity of 3NN with NASNASNAS sequence on N
      terminal was about tenfold higher than wild type (WT). Structural and biological
      stabilities of 3NN were also better than WT and residence time in mouse blood was
      longer than WT. M1 variants lacked growth activity though they are well
      glycosylated and secondary structure is very stable. Both of 3NN and OM1 with
      AAATPAPG on M1 associated with hIL-11R strongly. These results indicate N
      terminal and M1 variants will be expected for practical use as potent agonists or
      antagonists of hIL-11.

PMID- 27884520
TI  - Environmental benignity of a pesticide in soft colloidal hydrodispersive
      nanometric form with improved toxic precision towards the target organisms than
      non-target organisms.
AB  - Mosquito-borne diseases are of major concern as they cause devastating health
      effects, morbidity, and mortality in the human population. Conventional
      pesticides have failed to curb the mosquito population due to the development of
      insensitivity in mosquitoes. Hence, higher dosages of pesticides along with their
      toxic solubilizers have been employed, which have led to raise in pesticide
      pollution load, environmental toxicity, and human health concerns. As a
      realisation for the requirement of alternative pesticides, the present study has
      involved in the formulation of a hydrodispersive nanometric colloidal form of
      deltamethrin (NDM), a type-II pyrethroid pesticide, from its hydroimmisicible
      parental form (PDM). The mean hydrodynamic diameter of the droplets was found to
      be 30.6+/-4.6nm by dynamic light scattering study (DLS). High-resolution
      transmission electron micrographs have revealed the spherical structure of the
      droplets with a size range of 35-40nm. The NDM was found to possess sedimentation
      resistance, intrinsic and hydrodispersive stability. The toxicity of NDM and PDM
      was comparatively investigated on target organisms (Culex tritaeniorhynchus and
      Culex quinquefasciatus mosquitoes) and non-target organisms (Allium cepa -
      Bioindicator of toxicants and Rhizobium sp. - Soil bacteria). As comparative to
      PDM, NDM has exerted higher efficacy on adult mosquito and larval population,
      even at low-level concentrations. However, in the case of non-target organisms,
      the NDM toxicity was lower than PDM. Comprehensively, the study has concluded the
      potential advantage of formulating conventional pesticides into nanometric soft
      colloidal form for the improved toxic precision on target organisms (mosquitoes).
      This ensures the ability of NDM to combat against the mosquito population even at
      lower concentrations, thereby reducing the pesticide exposure load towards the
      environment and human population.

PMID- 27884521
TI  - The consequences of landscape change on fishing strategies.
AB  - We show how land-use change can affect fisher-harvesting behavior. We test
      whether fisher harvesting behavior can be predicted by landscape change patterns
      at local (~200km) and regional (~1200km) levels. Our data suggest that fishers
      harvesting in areas near tree plantations reduced benthic-invertebrate harvests
      in favor of demersal and pelagic finfish that are usually located further
      offshore. Fishers' management areas, which were near tree plantations, had higher
      chlorophyll-a values, and contained shellfish with more endobionts. Technology
      (owning a boat) and experience (age, years fishing, and alternative livelihoods)
      explained little in fisher-harvesting behavior. The flagship Chilean fisheries
      management program and seafood companies sourcing from these areas will need to
      respond to these new challenges. Despite complexities in designing cross-scale,
      social-ecological studies, we can no longer ignore the interconnectedness of
      commodities in the biosphere.

PMID- 27884522
TI  - Exposure to phthalates in children aged 5-7years: Associations with thyroid
      function and insulin-like growth factors.
AB  - This study aimed to evaluate the associations between phthalate concentrations
      and thyroid function in preschool children. We collected demographic data and
      biological samples from 216 children aged 5-7years. We calculated urinary
      concentrations of eight mono-phthalate metabolites (mPAEs) separately for
      children from urban and rural areas and investigated their associations with
      thyroid function and growth hormones. mPAE concentrations were higher in children
      from the urban area than in those from the rural area, and most mPAEs were
      positively associated with free triiodothyronine and free thyroxine. The insulin
      like growth factor 1 (IGF-1) concentration decreased 0.082ng/mL (95% confidence
      interval [CI]: -1.34, -0.113) with each 1ng/mL increase in monomethyl phthalate
      (MMP) and 0.132ng/mL (95% CI: -0.209, -0.055) with each 1ng/mL increase in mono-n
      butyl phthalate. The insulin-like growth factor binding protein 3 concentration
      decreased by 0.01mg/L (95% CI: -0.001, -0.000) or 0.01mg/L (95% CI: -0.003, 
      0.000) with each 1ng/mL increase in MMP or monoethyl phthalate, respectively.
      Exposure to some phthalates at 5-7years of age might interfere with thyroid
      hormones and growth.

PMID- 27884523
TI  - The anthroposphere as an anticipatory system: Open questions on steering the
      climate.
AB  - Climate change research and action counteracting it affect everyone and would
      involve cross-societal transformations reshaping the anthroposphere in its
      entirety. Scrutinizing climate-related science and policies, we recognize
      attempts to steer the evolution of climate according to expected (or modelled)
      futures. Such attempts would turn the anthroposphere into a large "anticipatory
      system", in which human society seeks to anticipate and, possibly, to govern
      climate dynamics. The chief aim of this discussion paper is to open a critical
      debate on the climate change paradigm (CCP) drawing on a strategic and systemic
      framework grounded in the concept of anticipatory system sensu Rosen (1991). The
      proposed scheme is ambitiously intended to turn an intricate issue into a complex
      but structured problem that is to say, to make such complexity clear and
      manageable. This framework emerges from concepts borrowed from different
      scientific fields (including future studies and system dynamics) and its
      background lies in a simple quantitative literature overview, relying upon a
      broad level of analysis. The proposed framework will assist researchers and
      policy makers in thinking of CCP in terms of an anticipatory system, and in
      disentangling its interrelated (and sometimes intricate) aspects. In point of
      fact, several strategic questions related to CCP were not subjected to an
      adequate transdisciplinary discussion: what are the interplays between physical
      processes and social-political interventions, who is the observer (what he/she is
      looking for), and which paradigm is being used (or who defines the desirable
      future). The proposed scheme allows to structure such various topics in an
      arrangement which is easier to communicate, highlighting the linkages in between,
      and making them intelligible and open to verification and discussion.
      Furthermore, ideally developments will help scientists and policy makers address
      the strategic gaps between the evidence-based climatological assessments and the
      plurality of possible answers as applied to the geopolitical contingencies.

PMID- 27884524
TI  - Increasing phytoplankton-available phosphorus and inhibition of macrophyte on
      phytoplankton bloom.
AB  - We assembled mesocosms to address the coherent mechanisms that an increasing
      phosphorus (P) concentration in water columns coupled with the phytoplankton
      bloom and identify the performance gap of regulating phytoplankton growth between
      two macrophyte species, Ceratophyllum demersum L. and Vallisneria spiralis L.
      Intense alkaline phosphatase activities (APA) were observed in the unplanted
      control, with their predominant part, phytoplankton APA (accounting for up to
      44.7% of the total APA), and another large share, bacterial APA. These correspond
      with the large average concentration of total phosphorus (TP), total dissolved
      phosphorus (TDP) and soluble reactive (SRP) as well as high phytoplankton density
      in the water column. The consistency among P concentrations, phytoplankton
      density and APA, together with the positive impact of phytoplankton density on
      total APA revealed by the structural equation modelling (SEM), indicates that
      facilitated APA levels in water is an essential strategy for phytoplankton to
      enhance the available P. Furthermore, a positive interaction between
      phytoplankton APA and bacteria APA was detected, suggesting a potential
      collaboration between phytoplankton and bacteria to boost available P content in
      the water column. Both macrophyte species had a prominent performance on
      regulating phytoplankton proliferation. The phytoplankton density and quantum
      yield in C. demersum systems were all significantly lower (33.8% and 24.0%) than
      those in V. spiralis systems. Additionally, a greater decoupling effect of C.
      demersum on the relationship between P, APA, phytoplankton density, bacteria
      dynamic and quantum yield was revealed by SEM. These results imply that the
      preferred tactic of different species could lead to the performance gap.

PMID- 27884525
TI  - Carbon accumulation rates recorded in the last 150years in tropical high mountain
      peatlands of the Atlantic Rainforest, SE - Brazil.
AB  - Peatlands are environmental matrices that store large amounts of organic carbon
      (TOC) and work as records of environmental changes. Recent record of organic
      carbon accumulated were assessed in two Forest National Parks, Itatiaia and Serra
      dos Orgaos in the Southeastern of Brazil. Based on organic and inorganic
      characterization, the cores from peatlands presented a predominance of organic
      material in an advanced stage of decomposition and those soils were classified as
      typical Haplosaprists Histosols. The combination of favorable topographic and
      climatic conditions led to rapid C accumulation across coastal mountain in the
      tropical peatlands studied, presenting an average accumulation rate of C, in the
      last century, of 194gCm-2yr-1 about 7 higher times than the rate found in boreal
      and subarctic peatlands, those higher values may be related to changes in the
      hydrological cycle occurred since 1950s.

PMID- 27884526
TI  - Impacts of changes in climate and landscape pattern on ecosystem services.
AB  - The restoration of degraded vegetation can effectively improve ecosystem
      services, increase human well-being, and promote regional sustainable
      development. Understanding the changing trends in ecosystem services and their
      drivers is an important step in informing decision makers for the development of
      reasonable landscape management measures. From 2001 to 2014, we analyzed the
      changing trends in five critical ecosystem services in the Xilingol Grassland,
      which is typical of grasslands in North China, including net primary productivity
      (NPP), soil conservation (SC), soil loss due to wind (SL), water yield (WY) and
      water retention (WR). Additionally, we quantified how climatic factors and
      landscape patterns affect the five ecosystem services on both annual and seasonal
      time scales. Overall, the results indicated that vegetation restoration can
      effectively improve the five grassland ecosystem services, and precipitation
      (PPT) is the most critical climatic factor. The impact of changes in the
      normalized difference vegetation index (NDVI) was most readily detectable on the
      annual time scale, whereas the impact of changes in landscape pattern was most
      readily detectable on the seasonal time scale. A win-win situation in terms of
      grassland ecosystem services (e.g., vegetation productivity, SC, WR and reduced
      SL) can be achieved by increasing grassland aggregation, partitioning the largest
      grasslands, dividing larger areas of farmland into smaller patches, and
      increasing the area of appropriate forest stands. Our work may aid policymakers
      in developing regional landscape management schemes.

PMID- 27884527
TI  - Source apportionment of size-fractionated particles during the 2013 Asian Youth
      Games and the 2014 Youth Olympic Games in Nanjing, China.
AB  - In this study, samples of size-fractionated particulate matter were collected
      continuously using a 9-size interval cascade impactor at an urban site in
      Nanjing, before, during and after the Asian Youth Games (AYG), from July to
      September of 2013, and the Youth Olympic Games (YOG), from July to September of
      2014. First, elemental concentrations, water-soluble ions including Cl-, NO3-,
      SO42-, NH4+, K+, Na+ and Ca2+, organic carbon (OC) and elemental carbon (EC) were
      analysed. Then, the source apportionment of the fine and coarse particulate
      matter was carried out using the chemical mass balance (CMB) model. The average
      PM10 concentrations were 90.4+/-20.0MUg/m3 during the 2013 AYG and 70.6+/
      25.3MUg/m3 during the 2014 YOG. For PM2.1, the average concentrations were 50.0+/
      12.8MUg/m3 in 2013 and 34.6+/-17.0MUg/m3 in 2014. Investigations showed that the
      average concentrations of particles declined significantly from 2013 to 2014, and
      concentrations were at the lowest levels during the events. Results indicated
      that OC, EC, sulfate and crustal elements have significant monthly and size-based
      variations. The major components, including crustal elements, water-soluble ions
      and carbonaceous aerosol accounted for 75.3-91.9% of the total particulate mass
      concentrations during the sampling periods. Fugitive dust, coal combustion dust,
      iron dust, construction dust, soil dust, vehicle exhaust, secondary aerosols and
      sea salt have been classified as the main emissions in Nanjing. The source
      apportionment results indicate that the emissions from fugitive dust, which was
      the most abundance emission source during the 2013 AYG, contributed to 23.0% of
      the total particle mass. However, fugitive dust decreased to 6.2% of the total
      particle mass during the 2014 YOG. Construction dust (14.7% versus 7.8% for the
      AYG and the YOG, respectively) and secondary sulfate aerosol (9.3% versus 8.0%
      for the AYG and the YOG, respectively) showed the same trend as fugitive dust,
      suggesting that the mitigation measures of controlling particles from the paved
      roads, construction and industry worked more efficiently during the YOG.

PMID- 27884528
TI  - Reducing future river export of nutrients to coastal waters of China in
      optimistic scenarios.
AB  - Coastal waters of China are rich in nitrogen (N) and phosphorus (P) and thus
      often eutrophied. This is because rivers export increasing amounts of nutrients
      to coastal seas. Animal production and urbanization are important sources of
      nutrients in Chinese rivers. In this study we explored the future from an
      optimistic perspective. We present two optimistic scenarios for 2050 (OPT-1 and
      OPT-2) for China. Maximized recycling of manure on land in OPT-1 and OPT-2, and
      strict sewage control in OPT-2 (e.g., all sewage is collected and treated
      efficiently) are essential nutrient strategies in these scenarios. We also
      analyzed the effect of the current policy plans aiming at "Zero Growth in
      Synthetic Fertilizers after 2020" (the CP scenario). We used the MARINA (a Model
      to Assess River Inputs of Nutrients to seAs) model to quantify dissolved N and P
      export by Chinese rivers to the Bohai Gulf, Yellow Sea and South China Sea and
      the associated coastal eutrophication potential (ICEP). The Global Orchestration
      (GO) scenario of the Millennium Ecosystem Assessment was used as a basis. GO
      projects increases in river export of dissolved N and P (up to 90%) between 2000
      and 2050 and thus a high potential for coastal eutrophication (ICEP>0). In
      contrast, the potential for coastal eutrophication is low in optimistic scenarios
      (ICEP<0). This is because in 2050 loads of most dissolved N and P in Chinese seas
      are around their levels of 1970. Maximizing manure recycling can reduce nutrient
      pollution of Chinese seas considerably. Sewage control is effective in reducing P
      export by rivers from urbanized areas. The CP scenario, on the other hand, shows
      that current policy plans may not be sufficient to avoid coastal eutrophication
      in the future. Our study may help policy makers in formulating strategies to
      ensure clean coastal waters in China in the future.

PMID- 27884529
TI  - Spatial distribution of heavy metals in the surface soil of source-control
      stormwater infiltration devices - Inter-site comparison.
AB  - Stormwater runoff infiltration brings about some concerns regarding its potential
      impact on both soil and groundwater quality; besides, the fate of contaminants in
      source-control devices somewhat suffers from a lack of documentation. The present
      study was dedicated to assessing the spatial distribution of three heavy metals
      (copper, lead, zinc) in the surface soil of ten small-scale infiltration
      facilities, along with several physical parameters (soil moisture, volatile
      matter, variable thickness of the upper horizon). High-resolution samplings and
      in-situ measurements were undertaken, followed by X-ray fluorescence analyses and
      spatial interpolation. Highest metal accumulation was found in a relatively
      narrow area near the water inflow zone, from which concentrations markedly
      decreased with increasing distance. Maximum enrichment ratios amounted to >20 in
      the most contaminated sites. Heavy metal patterns give a time-integrated vision
      of the non-uniform infiltration fluxes, sedimentation processes and surface flow
      pathways within the devices. This element indicates that the lateral extent of
      contamination is mainly controlled by hydraulics. The evidenced spatial structure
      of soil concentrations restricts the area where remediation measures would be
      necessary in these systems, and suggests possible optimization of their hydraulic
      functioning towards an easier maintenance. Heterogeneous upper boundary
      conditions should be taken into account when studying the fate of micropollutants
      in infiltration facilities with either mathematical modeling or soil coring field
      surveys.

PMID- 27884530
TI  - Heteroaggregation of graphene oxide nanoparticles and kaolinite colloids.
AB  - Graphene oxide (GO) is a material with rapid production growth, and consequently
      GO nanoparticles are expected to eventually penetrate subsurface formations,
      where fine mineral particles are in abundance. This study examines the
      heteroaggregation of GO nanoparticles with kaolinite (KGa-1b) colloids under
      various conditions. Dynamic batch experiments were conducted in solutions with
      different pH values (pH=4, 7, and 10), different ionic strengths (IS=7, 12, and
      27mM), and at three controlled temperatures (8, 14, and 25 degrees C). The
      experimental results showed that a relatively small amount of GO nanoparticles (5
      20% of the initial concentration) attached immediately onto KGa-1b colloids, and
      reached equilibrium in <20min. It was shown that neither temperature nor pH
      played a significant role in the attachment of GO nanoparticles onto KGa-1b
      colloids. In contrast, the attachment of GO nanoparticles onto KGa-1b colloids
      was shown to increase with increasing IS. Additionally, time-resolved dynamic
      light scattering (DLS) was used to identify the influence of IS on
      heteroaggregation between GO nanoparticles and KGa-1b colloids. The critical
      coagulation concentration (CCC) for the interaction between GO nanoparticles and
      KGa-1b colloids was 152mM (NaCl). The interaction energies were calculated, for
      all experimental conditions, by using measured zeta potentials and applying the
      classical DLVO theory. The equilibrium experimental data were fitted with a
      Freundlich isotherm, and the attachment kinetics were described very well with a
      pseudo-second-order model. Furthermore, thermodynamic analysis revealed that the
      attachment process was nonspontaneous and exothermic.

PMID- 27884531
TI  - Using groundwater age distributions to understand changes in methyl tert-butyl
      ether (MtBE) concentrations in ambient groundwater, northeastern United States.
AB  - Temporal changes in methyl tert-butyl ether (MtBE) concentrations in groundwater
      were evaluated in the northeastern United States, an area of the nation with
      widespread low-level detections of MtBE based on a national survey of wells
      selected to represent ambient conditions. MtBE use in the U.S. peaked in 1999 and
      was largely discontinued by 2007. Six well networks, each representing specific
      areas and well types (monitoring or supply wells), were each sampled at 10year
      intervals between 1996 and 2012. Concentrations were decreasing or unchanged in
      most wells as of 2012, with the exception of a small number of wells where
      concentrations continue to increase. Statistically significant increasing
      concentrations were found in one network sampled for the second time shortly
      after the peak of MtBE use, and decreasing concentrations were found in two
      networks sampled for the second time about 10years after the peak of MtBE use.
      Simulated concentrations from convolutions of estimates for concentrations of
      MtBE in recharge water with age distributions from environmental tracer data
      correctly predicted the direction of MtBE concentration changes in about 65% of
      individual wells. The best matches between simulated and observed concentrations
      were found when simulating recharge concentrations that followed the pattern of
      national MtBE use. Some observations were matched better when recharge was
      modeled as a plume moving past the well from a spill at one point in time.
      Modeling and sample results showed that wells with young median ages and narrow
      age distributions responded more quickly to changes in the contaminant source
      than wells with older median ages and broad age distributions. Well depth and
      aquifer type affect these responses. Regardless of the timing of decontamination,
      all of these aquifers show high susceptibility for contamination by a highly
      soluble, persistent constituent.

PMID- 27884532
TI  - Morphometric analysis of the folliculostellate cells and luteinizing hormone
      gonadotropic cells of the anterior pituitary of the men during the aging process.
AB  - The aim of this research was to quantify the changes in the morphology and
      density of the anterior pituitary folliculostellate (FS) and luteinizing hormone
      (LH) cells. Material was tissue of the pituitary gland of the 14 male cadavers.
      Tissue slices were immunohistochemically stained with monoclonal anti-LH antibody
      and polyclonal anti-S100 antibody for the detection of LH and FS cells,
      respectively. Digital images of the stained slices were afterwards
      morphometrically analyzed by ImageJ. Results of the morphometric analysis showed
      significant increase of the FS cells volume density in cases older than 70 years.
      Volume density of the LH cells did not significantly change, whereas their area
      significantly increased with age. Nucleocytoplasmic ratio of the LH cells
      gradually decreased and became significant after the age of 70. Finally, volume
      density of the FS cell significantly correlated with LH cells area and
      nucleocytoplasmic ratio. From all above cited, we concluded that in men, density
      and size of the FS cells increase with age. Long-term hypertrophy of the LH cells
      results in their functional decline after the age of 70. Strong correlation
      between FS cells and LH cells morphometric parameters might point to age-related
      interaction between these two cell groups.

PMID- 27884534
TI  - [Why is a special issue on obstructive sleep apnea-hypopnea syndrome in children
      necessary?]

PMID- 27884533
TI  - Thoron, radon and air ions spatial distribution in indoor air.
AB  - Spatial distribution of radioactive gasses thoron (Tn) and radon (Rn) in indoor
      air of 9 houses mostly during winter period of 2013 has been studied. According
      to properties of alpha decay of both elements, air ionization was also measured.
      Simultaneous continual measurements using three Rn/Tn and three air-ion active
      instruments deployed on to three different distances from the wall surface have
      shown various outcomes. It has turned out that Tn and air ions concentrations
      decrease with the distance increase, while Rn remained uniformly distributed.
      Exponential fittings function for Tn variation with distance was used for the
      diffusion length and constant as well as the exhalation rate determination. The
      obtained values were similar with experimental data reported in the literature.
      Concentrations of air ions were found to be in relation with Rn and obvious, but
      to a lesser extent, with Tn.

PMID- 27884535
TI  - [Developmental approach of executive functions: From infancy to adolescence].
AB  - Given the importance of the relationship between executive function (EF) and many
      aspects of child development - including the development of reasoning, emotion
      regulation, school performance, and wider self-regulation itself - research on
      the development of EF from infancy to the end of adolescence has become one of
      the scientific priorities of the last decade. Improving our knowledge on the
      maturative trajectory of EF and the functional weight of different internal and
      environmental factors, supposed to optimize their efficiency, can only promote a
      better understanding of EF and its role in the normal development of the child as
      well as of those at risk of poor outcome either because of neurodevelopmental
      disorders or psychopathological disorders. This article aims to update the recent
      literature in this area. It appears that executive function grows very gradually
      and evolves from a relatively simple and unitary model in young children to a
      more complex one - differentiated, integrated, and tripartite - in adolescence.

PMID- 27884536
TI  - [Chest X-ray and acute bronchiolitis: Are these indications decreasing?]
AB  - OBJECTIVE: A management protocol for infants hospitalized for acute
      bronchiolitis, established after the study conducted in our unit in 2012,
      recommends a chest X-ray when the clinical course is unusual or if a differential
      diagnosis is suspected. The goal of this study was to evaluate professional
      practices after the introduction of this new management protocol. STUDY DESIGN:
      Retrospective descriptive study in two pediatric units from October 2013 to March
      2015, including infants (0-23 months) hospitalized for their first episode of
      acute bronchiolitis without any underlying chronic condition. RESULT: Overall,
      599 infants were included (median age, 3.7 months, 54 % boys). Nearly six out of
      ten (n=355, 59.3 %) had at least one chest radiograph (38.5 % fewer than in
      2012). It was abnormal in 96.3 % of cases, revealing distension and/or bronchial
      wall thickening (56.7 %), focal opacity (23.5 %), or atelectasis (19.5 %). An X
      ray was performed out of the recommendations in 42.5 % of cases. The chest X-ray
      result led to management changes in 52 infants with prescription of antibiotics
      for pneumonia (86.5 %) and allowed the diagnosis of heart disease in one case
      (0.2 %). Management of acute bronchiolitis (X-ray and antibiotics) was
      statistically different between the two pediatric units. DISCUSSION: This
      protocol led to a significant decrease in the number of chest X-rays. However,
      many are still performed out of the recommendations, resulting in an increase of
      antibiotic use for pneumonia. CONCLUSION: The decrease in use of chest X-rays in
      acute bronchiolitis for hospitalized infants was significant but remains
      insufficient.

PMID- 27884537
TI  - [Nephrotic syndrome complicated by chylous ascites in a girl of 2 years and 8
      months old].
AB  - We report on a case of nephrotic syndrome with focal and segmental hyalinosis
      complicated by chylous ascites in a girl of 2 years and 8 months old. This pure
      nephrotic syndrome in its early stage was initially treated with intensive
      steroid treatment at 2mg/kg/day orally for 2 months, followed by a bolus of
      methylprednisolone. The persistence of proteinuria meant corticosteroid
      resistance. Renal biopsy then revealed focal and segmental hyalinosis. A
      recurrence of the edema-ascites syndrome was associated with macroscopic
      hematuria. Blood pressure and serum creatinine remained normal. Protidemia
      decreased to 28g/L, with severe hypoalbuminemia at 7g/L. The ascites puncture
      brought 1 L of aseptic and milky fluid, containing 0.22g/L of proteins, 20 IU/L
      of amylase, and 331g/L of total lipids. The treatment protocol included a
      hyperprotein diet, prednisone at 0.5mg/kg/day, cyclophosphamide at 2.5mg/kg/day
      for 1 month, then once every 2 days for 3 months, and repeated ascites punctures.
      After 12 ascites punctures performed every 15 days, a polyuric episode occurred
      and the ascites disappeared. Proteinuria persisted at a nephrotic rate up to the
      14th month, without impairment in kidney filtration function, and completely
      disappeared at the 20th month. After 5 years of follow-up, proteinuria remains
      undetectable and the physical exam is normal. The occurrence of chylous ascites
      during the nephrotic syndrome is a rare event. The formation of bowel
      lymphangiectasia, caused by a slowdown in venous return due to the pressure
      exerted by ascites, is probably the predominant mechanism.

PMID- 27884538
TI  - Oxygen therapy for management of periodic breathing : A theoretical approach.
AB  - A generalized framework for the generation of Periodic Breathing (PB), caused by
      delay variation, hypocapnia and sleep along with its management with oxygen
      therapy is presented. For this, a minimal model of respiratory regulation with
      cardiovascular component and two delays is proposed. This model is linearized and
      analyzed for stability by the proposed algorithms using Lyapunov-Krasovskii
      functional. Oscillation in this model is produced by the increase of delays, an
      increase of chemoreceptor gains (hypocapnia) and a decrease in minute ventilation
      (sleep induced PB). For delay variation, it is established that both the delays
      are responsible for oscillation in the system. However, maximum tolerable delay
      limit for the peripheral chemoreceptors is lower (0.3  min) compared to the
      central chemoreceptors (5.2  min). Stability analysis shows that application of
      additional oxygen is capable of suppressing the oscillation in the system by
      increasing the tolerable delay limit. Hypocapnia caused by hyperventilation is
      modeled by increased chemoreceptor gain. 50% increase in chemoreceptor gain along
      with 46% decrease in lung carbon dioxide storage makes the system oscillatory,
      which increases average minute ventilation by 19.42%. Application of additional
      oxygen makes the system stable. For sleep induced PB, it is shown that lowering
      minute ventilation causes oscillation in the system. A parameter is introduced to
      limit the minute ventilation in sleep, and its upper limit is calculated (8.7%
      drop in minute ventilation) for producing oscillation in the system. Application
      of higher oxygen makes the system stable by compensating for the reduction.
      Finally, two simulation studies are presented, showing the delay limits in
      hyperventilation and sleep condition. In these conditions, as the gains increase
      or minute ventilation decreases, tolerable delay limits become smaller.

PMID- 27884539
TI  - Intravesical chemotherapy use after radical nephroureterectomy: A national survey
      of urologic oncologists.
AB  - : To determine the use of prophylactic intravesical chemotherapy (pIVC) following
      radical nephroureterectomy (RNU) and barriers to utilization in a survey study of
      urologic oncologists. METHODS: A survey instrument was constructed, which queried
      respondents on professional experience, practice environment, pIVC use, and
      reasons for not recommending pIVC when applicable. The survey was electronically
      distributed to members of the Society of Urologic Oncology over an 8-week period.
      Survey software was used for analysis. RESULTS: The survey response rate was 22%
      (158 of 722). Half of the respondents were in practice for <=10 years, while 90%
      performed <=10 RNU cases annually. Of the 144 urologists regularly performing
      RNU, only 51% reported administering pIVC, including 22 exclusively in patients
      with a prior history of bladder cancer. One-third administered pIVC
      intraoperatively, whereas the remainder instilled pIVC at <=3 (7%), 4 to 7 (37%),
      8 to 14 (20%), and>14 (3%) days postoperatively. Almost all urologists noted
      giving a single instillation of pIVC. Agents included mitomycin-C (88%), thiotepa
      (7%), doxorubicin (3%), epirubicin (1%), and BCG (1%). Among respondents who did
      not administer pIVC, the most common reasons cited included lack of data
      supporting use (44%), personal preference (19%), and office infrastructure (17%).
      CONCLUSION: Only 51% of urologic oncologists report using pIVC in patients
      undergoing RNU. Reasons underlying this underutilization are multifactorial,
      thereby underscoring the need for continued dissemination of existing data and
      additional studies to support its benefits. Moreover, improving the logistics of
      pIVC administration may help to increase utilization rates.

PMID- 27884540
TI  - JANAC 2017 and Beyond.

PMID- 27884541
TI  - Connecting Homogalacturonan-Type Pectin Remodeling to Acid Growth.
AB  - According to the 'acid growth theory', cell wall acidification controls cell
      elongation, therefore plant growth. This notably involves changes in cell wall
      mechanics through modifications of cell wall polysaccharide structure. Recently,
      advances in cell biology showed that changes in cell elongation rate can be
      mediated by the remodeling of pectins, and in particular of homogalacturonans
      (HGs). Their demethylesterification appears to be a key element controlling the
      chemistry and the rheology of the cell wall. We postulate that precise and
      dynamic modulation of extracellular pH plays a central role in the control of HG
      modifying enzyme activities, and in particular those of pectin methylesterases
      and polygalacturonases. We propose that acid growth requires dynamic HG
      remodeling through the tight control of cell wall pH.

PMID- 27884542
TI  - Corrigendum to "Abnormal cortical sources of resting state
      electroencephalographic rhythms in single treatment-naive HIV individuals: A
      statistical z-score index" [Clin. Neurophysiol. 127 (2016) 1803-1812].

PMID- 27884543
TI  - Immunometabolism: Is it under the eye of the clock?
AB  - Molecular clocks allow an organism to track time of day, providing the means to
      anticipate and respond to the daily changes within the environment. In mammals
      the molecular clock consists of a network of proteins that form auto-regulatory
      feedback loops that drive rhythms in physiology and behavior. In recent times the
      extent to which the molecular clock controls key metabolic and immune pathways
      has begun to emerge. For example, the main clock protein BMAL1 has been linked to
      mitochondrial metabolism, mitochondrial dynamics and various host defense
      pathways. The molecular clock may function to integrate daily metabolic changes
      driven by feeding-fasting to immune function and output. Understanding how the
      clock intersects with metabolic pathways within immune cells to affect immune
      phenotypes will have broad implications for the management of metabolic,
      inflammatory and infectious diseases.

PMID- 27884544
TI  - Pancreas fistula risk prediction: implications for hospital costs and payments.
AB  - BACKGROUND: As payment models evolve, disease-specific risk stratification may
      impact patient selection and financial outcomes. This study sought to determine
      whether a validated clinical risk score for post-operative pancreatic fistula
      (POPF) could predict hospital costs, payments, and profit margins. METHODS: A
      multi-institutional cohort of 1193 patients undergoing pancreaticoduodenectomy
      (PD) were matched to an independent hospital where cost, in US$, and payment data
      existed. An analytic model detailed POPF risk and post-operative sequelae, and
      their relationship with hospital cost and payment. RESULTS: Per-patient hospital
      cost for negligible-risk patients was $37,855. Low-, moderate-, and high- risk
      patients had incrementally higher hospital costs of $38,125 ($270; 0.7% above
      negligible-risk), $41,128 ($3273; +8.6%), and $41,983 ($3858; +10.9%),
      respectively. Similarly, hospital payment for negligible-risk patients was
      $42,685/patient, with incrementally higher payments for low-risk ($43,265;
      +1.4%), moderate-risk ($45,439; +6.5%) and high-risk ($46,564; +9.1%) patients.
      The lowest 30-day readmission rates - with highest net profit - were found for
      negligible/low-risk patients (10.5%/11.1%), respectively, compared with
      readmission rates of moderate/high-risk patients (15%/15.7%). CONCLUSION:
      Financial outcomes following PD can be predicted using the FRS. Such prediction
      may help hospitals and payers plan for resource allocation and payment matched to
      patient risk, while providing a benchmark for quality improvement initiatives.

PMID- 27884545
TI  - A survey of current practices and barriers to expanding laparoscopic HPB surgery
      in Canada.
AB  - BACKGROUND: The purpose of this survey was to determine the extent to which
      laparoscopy is used in hepatopancreatobiliary (HPB) resections in Canada, and to
      assess HPB surgeons' attitudes and their perceived barriers to its further
      adoption. METHODS: Using an electronic questionnaire, 68 Canadian
      Hepatopancreatobiliary Association (CHPBA) surgical members were surveyed. The
      questionnaire consisted of 12 questions regarding: surgeon demographics, the use
      and limitations of laparoscopy in their practice, and interest in increasing the
      use of laparoscopic techniques. RESULTS: The survey response rate was 75%. Of the
      51 respondents, 86% reported performing minor laparoscopic resections such as
      hepatic wedge resections. Only 23% of surgeons reported performing laparoscopic
      liver lobectomies. Eighty-two percent of respondents indicated a wish to increase
      the use of laparoscopy in their practice. Barriers identified included operating
      time constraints (61%), a lack of equipment (41%) and lack of adequate training
      (43%). DISCUSSION: This survey demonstrates that currently, most Canadian HPB
      surgeons use laparoscopy for minor HPB resections; however, there is a strong
      desire to expand the use of minimally invasive techniques amongst Canadian HPB
      surgeons. Training centered on addressing the limitations and barriers to the
      uptake of minimally invasive techniques in HPB surgery are needed.

PMID- 27884547
TI  - Expression of concern.

PMID- 27884546
TI  - [Results of trabeculectomy with anti-VGEF therapy in the treatment of neovascular
      glaucoma secondary to retinal vein occlusion (report of 21 cases followed at
      Bukavu Eye Clinic from January 1 to December 31th, 2015)].
AB  - PURPOSE: To evaluate the results of anti-VGEF with trabeculectomy in the
      treatment of neovascular glaucoma, a severe complication of retinal vein
      occlusion (RVO). PATIENTS AND METHODS: This is a prospective case series of
      consecutive patients with neovascular glaucoma secondary to retinal vein
      occlusion. All patients underwent panretinal photocoagulation and a mean of 3
      anti-VEGF injections prior to trabeculectomy. Ophthalmic parameters were recorded
      pre- and postoperatively: visual acuity (VA), intraocular pressure (IOP), iris
      examination, gonioscopy and fundus examination, and as necessary, fluorescein
      angiography. Minimum follow-up was 9 months. RESULTS: Twenty-one eyes of 21
      patients were included. The mean preoperative intraocular pressure was 38mmHg (31
      45mmHg). Postoperatively, the mean IOP was 15mmHg (13-19mmHg). IOP reduction was
      observed in all eyes after surgery and stayed finally stabilized in nineteen eyes
      (90.5 %). The rubeosis had definitively disappeared an average of two weeks after
      injection, but VA decreased in all patients. Nineteen patients (90.5 %)
      maintained preservation of their eyes. Two eyes underwent evisceration.
      CONCLUSION: In most cases, trabeculectomy with anti-VGEF halted anterior segment
      neovascularization. It allowed for surgery on a quiet, normotensive eye, with
      good postoperative results. While functional rehabilitation was not achieved, the
      globe was able to be preserved in 90.5 % of cases.

PMID- 27884548
TI  - Infantile neuroaxonal dystrophy and PLA2G6-associated neurodegeneration: An
      update for the diagnosis.
AB  - Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder
      characterized by infantile onset of rapid motor and cognitive regression and
      hypotonia evolving into spasticity. Recessively inherited mutations of the PLA2G6
      gene are causative of infantile neuroaxonal dystrophy and other PLA2G6-associated
      neurodegeneration, which includes conditions known as atypical neuroaxonal
      dystrophy, Karak syndrome and early-onset dystonia-parkinsonism with cognitive
      impairment. Phenotypic spectrum continues to evolve and genotype-phenotype
      correlations are currently limited. Due to the overlapping phenotypes and
      heterogeneity of clinical findings characterization of the syndrome is not always
      achievable. We reviewed the most recent clinical and neuroradiological
      information in the way to make easier differential diagnosis with other
      degenerative disorders in the paediatric age. Recognizing subtle signs and
      symptoms is a fascinating challenge to drive towards better diagnostic and
      genetic investigations.

PMID- 27884549
TI  - Time before anti-Toxoplasma IgG seroconversion detection by 7 commercial assays
      in French pregnant women.
AB  - We assessed the ability to early detect a toxoplasmic seroconversion between 1
      immunoblot (LDBIO II(r)) and 6 automated assays (TGS TA(r), Architect(r), Vidas
      II(r), Liaison II(r), Platelia(r), and Elecsys(r)), comparing the time before
      anti-Toxoplasma gondii IgG detection during infection in pregnant women. From
      2007 to 2015, 620 sera of 269 women were included. The median durations before
      positive IgG detection with Vidas II(r), Liaison II(r), Platelia(r), and
      Elecsys(r) were significantly longer than Architect(r) with differential times
      from 11 to 28days (P<0.001). This time was significantly shortened by the use of
      LDBIO(r), resulting in a saving of 13days (P<0.001). The detection of a positive
      rate of IgG with TGS TA(r) was as early as Architect(r) (P=0.105). The ability to
      early detect a toxoplasmic seroconversion is not equivalent between the assays
      and has to be considered when selecting the reagents to reduce the time to
      therapeutic intervention.

PMID- 27884550
TI  - Effects of Changing the Amount and Source of Dietary Carbohydrates on Symptoms
      and Dietary Satisfaction Over a 1-Year Period in Subjects with Type 2 Diabetes:
      Canadian Trial of Carbohydrates in Diabetes (CCD).
AB  - OBJECTIVES: To determine the long-term effects of changing the amount or source
      of dietary carbohydrate on quality of life (QOL), symptoms and dietary
      satisfaction in people with type 2 diabetes. METHODS: Subjects with diabetes
      treated by diet alone (n=162) were randomly assigned to high-carbohydrate/high
      glycemic-index (HGI) diets; high-carbohydrate/low-glycemic-index (LGI) diets; or
      lower-carbohydrate/high-monounsaturated-fat (LC) diets for 1 year. We measured
      QOL at baseline and at study's end, and we measured symptoms and dietary
      satisfaction quarterly. RESULTS: The HGI, LGI and LC diets contained,
      respectively, 47+/-1, 52+/-1 and 40+/-1% energy carbohydrate; 30+/-1, 27+/-1 and
      40+/-1% fat with GI 64+/-0.4, 55+/-0.4 and 59+/-0.4. Significantly more
      participants reported increased flatulence on LGI than on LC and HGI diets at 3
      months (41%, 19%, 14%; p<0.05), but not at 12 months (29%, 17%, 17%; ns).
      Abdominal distension was more severe (46% vs. 14%, 19%; p<0.05), and headache
      less severe (8% vs. 22%, 23%; p<0.05) on LGI than on both other diets. Increased
      appetite was more severe on LC (33%) than on HGI diets (14%, p<0.05). Joint/limb
      pains were less severe on LGI (16%) than HGI (28%) diets. LC elicited more severe
      gloomy thoughts (23%) than LGI (4%; p<0.05) but greater dietary-satisfaction
      (70%; p<0.05) than LGI (40%) and HGI (48%) diets. For all diets, glycated
      hemoglobin (A1C) levels increased less in those who gained less weight, had less
      increased appetite and were more satisfied with the enjoyment obtained from
      eating. CONCLUSIONS: Each diet elicited increased severity of 1 or more symptoms
      than the other diets. Although overall dietary satisfaction was greater on the
      40% carbohydrate diet than on the 50% carbohydrate diet, the LGI diet was no less
      satisfying than the HGI diet. Changes in appetite and dietary satisfaction may
      influence body weight and glycemic control, or vice-versa.

PMID- 27884551
TI  - Resting-state Abnormalities in Heroin-dependent Individuals.
AB  - Drug addiction is a major health problem worldwide. Recent neuroimaging studies
      have shed light into the underlying mechanisms of drug addiction as well as its
      consequences to the human brain. The most vulnerable, to heroin addiction, brain
      regions have been reported to be specific prefrontal, parietal, occipital, and
      temporal regions, as well as, some subcortical regions. The brain regions
      involved are usually linked with reward, motivation/drive, memory/learning,
      inhibition as well as emotional control and seem to form circuits that interact
      with each other. So, along with neuroimaging studies, recent advances in resting
      state dynamics might allow further assessments upon the multilayer complexity of
      addiction. In the current manuscript, we comprehensively review and discuss
      existing resting-state neuroimaging findings classified into three overlapping
      and interconnected groups: functional connectivity alterations, structural
      deficits and abnormal topological properties. Moreover, behavioral traits of
      heroin-addicted individuals as well as the limitations of the currently available
      studies are also reviewed. Finally, in need of a contemporary therapy a
      multimodal therapeutic approach is suggested using classical treatment practices
      along with current neurotechonologies, such as neurofeedback and goal-oriented
      video-games.

PMID- 27884553
TI  - Maps of systematic variation in renal replacement therapy in Catalonia (2002
      2012).
AB  - INTRODUCTION: Variations in the use of healthcare services can be defined as
      systematic variations of adjusted rates for certain aggregation levels of the
      population. The study analyses how renal replacement therapy (RRT) is used,
      identifying RRT variability in Catalonia from 2002 to 2012. MATERIAL AND METHODS:
      Ecological study by health area using data from the Catalan renal registry. We
      present incident rates, standardised incidence ratios and prevalence, while
      variability was calculated through direct and indirect standardisation methods.
      RESULTS: From 2002 until 31/12/2012, 10,784 patients initiated RRT in Catalonia:
      9,238 on haemodialysis (HD) (50 treatments per 100,000 people 2010/2012), 1,076
      on peritoneal dialysis (PD) (8.2 treatments per 100,000 people 2010/2012) and 470
      received an early kidney transplant (KT) (4.4 treatments per 100,000 people
      2010/2012). Over the 10 years, the HD cumulative incidence rate fell (7%), while
      the PD and KT incidence rates increased (63% and 177%, respectively); both are
      higher in young patients (<45 years). 4,750 patients received a kidney transplant
      in this period, 49% of which were aged between 45 and 65 years. There were no
      significant differences in variability in HD (RV5-95=1.3; Empirical Bayes [EB]~
      0), or in the prevalence of KT (RV5-95=1.4; EB ~ 0). Nevertheless, we found
      significant geographical variability in PD; notably in the districts of the
      province of Lerida, where the number of cases observed was greater than expected
      (RV5-95=4.01; EB=0.08). CONCLUSION: Although there was a notable rise in PD and
      early KT incidence rates, PD is still underused when compared to international
      recommendations. No territorial variability was found for HD or KT, but the use
      of PD was found to be higher in Lerida than in other areas. To reduce PD
      territorial variability and increase the uptake of this technique in the other
      regions, we propose 3initiatives: The development of RRT support tools for shared
      decision-making, the encouragement of specific PD professional training and the
      promotion of PD through complementary reimbursement systems.

PMID- 27884554
TI  - Segmental tuberous sclerosis in a patient with chronic kidney disease.

PMID- 27884552
TI  - Estimated saving of antibiotics in pharyngitis and lower respiratory tract
      infections if general practitioners used rapid tests and followed guidelines.
AB  - INTRODUCTION: General practitioners (GP) in Spain do not have access to rapid
      tests and adherence to guidelines is usually suboptimal. The aim of the study is
      to evaluate the estimated number of antibiotics that could have been saved if GPs
      had appropriately used these tests and had followed the guidelines. DESIGN:
      Observational study. SETTING: Primary care centres from eight Autonomous
      Communities in Spain. PARTICIPANTS: GPs who had not participated in previous
      studies on rational use of antibiotics. INTERVENTION: GPs registered all the
      cases of pharyngitis and lower respiratory tract infections (LRTI) during 15
      working days in 2015, by means of a 47-item audit. MAIN MEASUREMENTS: Actual GPs'
      antibiotic prescription and estimated number of antibiotics that could have been
      saved according to recent guidelines. RESULTS: A total of 126 GPs registered 1012
      episodes of pharyngitis and 1928 LRTIs. Antibiotics were given or patients were
      referred in 497 patients with pharyngitis (49.1%) and 963 patients with LRTI
      (49.9%). If GPs had appropriately used rapid antigen detection tests and C
      reactive protein tests and had strictly followed current guidelines, antibiotics
      would have been given to 7.6% and 15.1%, respectively, with an estimated saving
      of 420 antibiotics in patients with sore throat (estimated saving of 84.5%; 95%
      CI: 81.1-87.4%) and 672 antibiotics in LRTIs (estimated saving of 69.8%,95% CI:
      67.1-72.5%). CONCLUSIONS: GP adherence to guidelines and a correct introduction
      of rapid tests in clinical practice in Spain could result in a considerable
      saving of unnecessary prescription of antibiotics in pharyngitis and LRTIs.

PMID- 27884555
TI  - After 10years of JAK2V617F: Disease biology and current management strategies in
      polycythaemia vera.
AB  - The JAK2V617F mutation accounts for the vast majority of patients with
      polycythaemia vera (PV) and around half of those with other Philadelphia-negative
      myeloproliferative neoplasms. Since its discovery in 2005, numerous insights have
      been gained into the pathways by which JAK2V617F causes myeloproliferation,
      including activation of JAK-STAT signalling but also through other canonical and
      non-canonical pathways. A variety of mechanisms explain how this one mutation can
      be associated with distinct clinical disorders, demonstrating how constitutional
      and acquired factors may interact in the presence of a single mutation to
      determine disease phenotype. Important biological questions remain unanswered in
      PV, in particular how JAK2V617F affects stem cell function and what mechanisms
      drive myelofibrotic and leukaemic transformation. Whilst current management is
      largely centred on prevention of cardiovascular events, future therapies must aim
      to target the JAK2-mutant clone, to reverse the underlying marrow pathology and
      to address the risk of transformation events.

PMID- 27884556
TI  - [Effectiveness of non-pharmacological interventions in the quality of life of
      caregivers of Alzheimer].
AB  - OBJECTIVE: Explore the effectiveness of non-pharmacological interventions to
      improve the quality of life of family caregivers of Alzheimer's patients.
      METHODS: We conducted a systematic review, in pairs, in the following databases:
      PubMed, Scopus, CINAHL, PsycINFO, WOS, Cochrane Library, IME, Cuiden Plus and
      Dialnet. Inclusion criteria were: 1. Studies published between 2010-2015. 2.
      Language: English, Portuguese and Spanish. 3. Randomized controlled clinical
      trials. 4. Score greater than or equal to 3 on the Jadad scale. RESULTS: 13
      studies were included. Four performed a psychosocial intervention with family
      caregivers, three psychotherapeutic, two psychoeducational, two multicomponent,
      one educational and another with mutual support groups. The tools to assess
      quality of life: three studies used the Health Status Questionnaire (HSQ), three
      EuroQol-5D (two only used the EVA), two health questionnaire SF-36, two WHOQOL
      BREF, two Quality of Life SF-12 and one Perceived Quality of Life Scale (PQoL).
      Regarding the effectiveness of non-pharmacological interventions, five studies
      obtained favorable results in the quality of life after psychotherapeutic
      interventions and community-type multicomponent training. CONCLUSION: The
      diversity of non-pharmacological interventions used and contents, differences in
      the number of sessions and hours, and variability of valuation tools used to
      measure quality of life of family caregivers, leads us to reflect on the
      appropriateness to standardize criteria, for the sake to improve clinical
      practice.

PMID- 27884557
TI  - Laryngeal Trauma Following an Inhalation Injury: A Review and Case Report.
AB  - The primary concern when managing a patient with inhalation injury is security of
      the airway. Airflow may be impeded by both edema of the upper airway and
      reduction of oxygen delivery to the lower respiratory tract. Although there has
      been much discussion regarding management of the latter, the focus of this
      article is the management of the former. This review aimed to determine the
      optimum management in burn victims with upper airway inhalation injury as an
      attempt to prevent laryngeal trauma leading to long-term voice disorders and
      upper airway dyspnea. We describe the case of a 57-year-old woman with
      significant inhalation injury and discuss the natural progression of her injuries
      and the laryngeal controversies surrounding her care. We conclude with advice on
      the optimal management of this condition based on our experience, combined with
      current best evidence.

PMID- 27884558
TI  - Reply to the Letter to Editor "Hyposmolarity may be also associated with worse
      outcomes in patients with heart failure".

PMID- 27884559
TI  - Noninvasive measurement of coronary flow velocity reserve during inotropic
      stimulation as an additional tool for hemodynamic assessment of myocardial
      bridging.

PMID- 27884560
TI  - Cardiac imaging stress techniques: How fishing in the high-tech pot.

PMID- 27884561
TI  - Survival after cardiac arrest in Greece.

PMID- 27884562
TI  - Endothelial overactivity maybe a contributing factor in athletes with vasovagal
      syncope.

PMID- 27884563
TI  - Combined associations of sedentary behavior and cardiorespiratory fitness on
      cognitive function among older adults.
AB  - BACKGROUND: Sedentary behavior, cardiorespiratory fitness, cognition and age are
      interrelated and associated with cardiovascular function. No study, however, has
      specifically evaluated the independent and combined associations of
      cardiorespiratory fitness and sedentary behavior on cognition, which was this
      study's purpose. METHODS: Data from the 1999-2002 NHANES were used (N=2451; 60
      85yrs). Sedentary behavior was assessed via self-report; cardiorespiratory
      fitness was assessed from a medical-related algorithm; and cognition function was
      assessed from the Digit Symbol Substitution Test (DSST). RESULTS: Being in the
      bottom quartile for sedentary behavior (beta=2.13; 95% CI: 0.49-3.77; P=0.01) and
      the top quartile for cardiorespiratory fitness (beta=7.48; 95% CI: 5.4-9.5;
      P<0.001) were independently associated with higher cognitive function. In the
      additive model, those with an index score of 1 (vs. 0) and 2 (vs. 0),
      respectively, had a 3.87 (beta=3.87; 95% CI: 1.76-5.98; P=0.001) and 10.40
      (beta=10.4; 95% CI: 7.31-13.5; P<0.001) higher DSST score. CONCLUSION: High
      cardiorespiratory fitness and low sedentary behavior were jointly associated with
      the highest cognitive function. This has important cardiovascular implications as
      a progression of neurocognitive impairment is associated with increasingly severe
      manifestations of cardiovascular disease.

PMID- 27884564
TI  - Endothelial dysfunction in takotsubo syndrome.

PMID- 27884565
TI  - Reply to letter to the Editor "Cardiac Imaging Stress Techniques: How fishing in
      the high-tech pot".

PMID- 27884566
TI  - Reply to Letter to the Editor "Concern on article "Predicting procedure
      successful rate and 1-year patency after endovascular recanalization for chronic
      carotid artery occlusion by CT angiography"".

PMID- 27884567
TI  - Particulars of diabetes mellitus may matter in patients with takotsubo syndrome.

PMID- 27884568
TI  - YKL-40 and other indicators of inflammation in coronary collateral development
      and SYNTAX score.

PMID- 27884569
TI  - Eye spy with my little eye: Motivational relevance of visual stimuli guide eye
      movements at different processing stages.
AB  - Visual stimuli may be selected for priority at different stages within the
      processing stream, depending on how motivationally relevant they are to the
      perceiver. Here we examine the extent to which individual differences in
      motivational relevance of task-irrelevant images (spider, crash, baby, food and
      neutral) guide eye-movements to a simple "follow the cross" task in 96
      participants. We found affective images vs. neutral images to be generally more
      distracting, as shown by faster first saccade latencies and greater deviation in
      the final landing position from the target cross. The most arousing images
      (spider and food), compared to neutral images, showed the largest trajectory
      deviations of the first saccade. Fear of spiders specifically predicted greater
      deviation in the final landing position on spider images. These results suggest
      that attentional biases towards arousing and motivationally relevant stimuli may
      occur at different processing stages.

PMID- 27884570
TI  - A GC-MS method for the detection and quantitation of ten major drugs of abuse in
      human hair samples.
AB  - A sensitive analytical method has been developed in order to identify and
      quantify major drugs of abuse (DOA), namely morphine, codeine, 6
      monoacetylmorphine, cocaine, ecgonine methyl ester, benzoylecgonine, amphetamine,
      methamphetamine, methylenedioxymethamphetamine and methylenedioxyamphetamine in
      human hair. Samples of hair were extracted with methanol under ultrasonication at
      50 degrees C after a three step rinsing process to remove external contamination
      and dirt hair. Derivatization with BSTFA was selected in order to increase
      detection sensitivity of GC/MS analysis. Optimization of derivatization
      parameters was based on experiments for the selection of derivatization time,
      temperature and volume of derivatising agent. Validation of the method included
      evaluation of linearity which ranged from 2 to 350ng/mg of hair mean
      concentration for all DOA, evaluation of sensitivity, accuracy, precision and
      repeatability. Limits of detection ranged from 0.05 to 0.46ng/mg of hair. The
      developed method was applied for the analysis of hair samples obtained from three
      human subjects and were found positive in cocaine, and opiates.

PMID- 27884571
TI  - Inhibition of listeriolysin O oligomerization by lutein prevents Listeria
      monocytogenes infection.
AB  - The foodborne pathogenic bacterial species Listeria monocytogenes (L.
      monocytogenes) has caused incalculable damages to public health, and its
      successful infection requires various virulence factors, including Listeriolysin
      O (LLO). By forming pores in phagosomal membranes and even in some organelles,
      LLO plays an indispensable role in the ability of L. monocytogenes to escape from
      host immune attacks. Because of its critical role, LLO offers an appropriate
      therapeutic target against L. monocytogenes infection. Here, lutein, a natural
      small molecule existing widely in fruits and vegetables, is demonstrated as an
      effective inhibitor of LLO that works by blocking its oligomerization during
      invasion without showing significant bacteriostatic activity. Further assays
      applying lutein in cell culture models of invasion and in animal models showed
      that lutein could effectively inhibit L. monocytogenes infection. Overall, our
      results indicate that lutein may represent a promising and novel therapeutic
      agent against L. monocytogenes infection.

PMID- 27884572
TI  - Tick-borne encephalitis virus neutralization by high dose intravenous
      immunoglobulin.
AB  - Tick-borne encephalitis (TBE) is a potentially lethal neuroinfection in humans,
      caused by TBE virus (TBEV). Currently, there are no approved therapeutic agents
      to treat TBE. Previously, it was suggested that application of high dose
      intravenous immunoglobulin (IVIG) may pose potentially successful treatment for
      severe cases of TBE. In this study, we determined the titers of TBEV-neutralizing
      antibodies in two IVIG lots originating from the same manufacturer, and tested
      their ability to treat a lethal TBEV-infection in a mouse model. Using an in
      vitro assay, more than 100-fold difference in TBEV-neutralizing capacity was
      demonstrated between the two individual IVIG lots. High TBEV-neutralizing
      activity of IVIG containing TBEV-specific antibody was confirmed in two different
      human neural cell lines, but IVIG without TBEV-specific antibodies had no or
      little effect on virus titers in the culture. In TBEV-infected mice, 90% of
      protection was achieved when the mice were treated with IVIG containing higher
      titers of TBEV-specific antibodies, whereas no immunotherapeutic effect was seen
      when mice were treated with IVIG without TBEV-specific antibodies. No antibody
      dependent enhancement of TBEV infectivity induced by cross-reactive antibodies or
      by virus-specific antibodies at neutralizing or sub-neutralizing levels was
      observed either in cell culture or in TBEV-infected mice treated with any of the
      IVIG preparations. The results indicate that IVIG lots with high TBEV antibody
      titers might represent a post-exposure prophylaxis or first-line effective
      therapy of patients with a severe form of TBE.

PMID- 27884573
TI  - Analysing how negative emotions emerge and are addressed in veterinary
      consultations, using the Verona Coding Definitions of Emotional Sequences (VR
      CoDES).
AB  - OBJECTIVE: To explore the applicability, need for modifications and reliability
      of the VR-CoDES in a veterinary setting while also gaining a deeper understanding
      of clients' expressions of negative emotion and how they are addressed by
      veterinarians. METHODS: The Verona Coding Definitions of Emotional Sequences for
      client cues and concerns (VR-CoDES-CC) and health provider responses (VR-CoDES-P)
      were used to analyse 20 audiotaped veterinary consultations. Inter-rater
      reliability was established. The applicability of definitions of the VR-CoDES was
      identified, together with the need for specific modifications to suit veterinary
      consultations. RESULTS: The VR-CoDES-CC and VR-CoDES-P generally applied to
      veterinary consultations. Cue and concern reliability was found satisfactory for
      most types of cues, but not for concerns. Response reliability was satisfactory
      for explicitness, and for providing and reducing space for further disclosure.
      Modifications to the original coding system were necessary to accurately reflect
      the veterinary context and included minor additions to the VR-CoDES-CC.
      CONCLUSION: Using minor additions to the VR-CoDES including guilt, reassurance
      and cost discussions it can be reliably adopted to assess clients' implicit
      expressions of negative emotion and veterinarians' responses. PRACTICE
      IMPLICATIONS: The modified VR-CoDES could be of great value when combined with
      existing frameworks used for teaching and researching veterinary communication.

PMID- 27884574
TI  - Corrigendum to "Unveiling the functional diversity of the alpha/beta hydrolase
      superfamily in the plant kingdom" [Curr Opin Struct Biol 2016, 41:233-246].

PMID- 27884575
TI  - Brugada Pattern Caused by a Flecainide Overdose.
AB  - BACKGROUND: Brugada pattern can be found on the electrocardiogram (ECG) of
      patients with altered mental status, usually with fever or drug intoxication.
      Diagnosis remains challenging, because the ECG changes are dynamic and variable.
      In addition, triggers are not always clearly identified. In patients with atrial
      fibrillation (AF), the use of class IC antidysrhythmic drugs can unmask a Brugada
      pattern on the ECG, especially if combined with other medications acting on
      sodium channels. CASE REPORT: A 62-year-old man with a medical history of AF was
      admitted to our emergency department for altered mental status. The ECG at the
      time of admission showed a Brugada pattern, triggered by a flecainide overdose
      (about 1 g), in association with an unknown dose of lamotrigine and quetiapine.
      After discontinuation of all medications, the Brugada pattern disappeared and his
      ECG showed no abnormalities. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?:
      In patients with AF, the use of class IC antidysrhythmic drugs, if overdosed, can
      trigger a Brugada ECG pattern, and therefore it can increase the risk for
      malignant dysrhythmias. It is important to provide, to all patients with a
      Brugada ECG pattern, a list of drugs to avoid, and to underline the synergistic
      interplay between drugs, taking into consideration all patients' comorbidities.

PMID- 27884576
TI  - Extracorporeal Life Support for Refractory Cardiac Arrest from Accidental
      Hypothermia: A 10-Year Experience in Edinburgh.
AB  - BACKGROUND: Cardiac arrest caused by accidental hypothermia is a rare phenomenon
      with a significant mortality rate if untreated. The consensus is that these
      patients should be rewarmed with extracorporeal life support (ECLS) with the
      potential for excellent survival and neurologic outcomes. However, given the lack
      of robust data and clinical trials, the optimal management of such patients
      remains elusive. OBJECTIVE: In this single-center study, we looked at the
      outcomes of all adult patients undergoing salvage ECLS for cardiac arrest caused
      by accidental hypothermia over a 10-year period from June 2006 to June 2016.
      METHODS: These data were obtained from the Royal Infirmary of Edinburgh
      cardiothoracic surgery database. The patients' hard copy case notes, TrakCare
      (InterSystems Corp, Cambridge, MA), picture archiving and communications system
      (PACS), and WardWatcher databases were used to cross-check the accuracy of the
      acquired data. RESULTS: Eleven patients met the inclusion criteria. The etiology
      of hypothermia was exposure to cold air (64%) and cold water immersion (36%). Two
      (18%) were treated with extracorporeal membrane oxygenation and the rest with
      cardiopulmonary bypass. The mean age was 51 years (range 32-73), and the mean
      core body temperature on admission was 20.6 degrees C (range <18-24 degrees C).
      The overall survival rate to hospital discharge was 72%, with 75% of survivors
      having no chronic neurologic impairment. CONCLUSION: Our case series shows the
      remarkable salvageability of patients suffering prolonged cardiac arrest caused
      by accidental hypothermia, particularly in the absence of asphyxia, trauma, or
      severe hyperkalemia. ECLS is a safe and effective rewarming treatment and should
      be used to aggressively manage this patient group.

PMID- 27884577
TI  - Low-Pressure Pericardial Tamponade: Case Report and Review of the Literature.
AB  - BACKGROUND: Focused cardiac ultrasound (FoCUS) is accurate for determining the
      presence of a pericardial effusion. Using FoCUS to evaluate for pericardial
      tamponade, however, is more involved. Many experts teach that tamponade is
      unlikely if the inferior vena cava (IVC) shows respiratory variation and is not
      distended. CASE REPORT: A 53-year-old woman presented to the emergency department
      (ED) with severe orthostatic hypotension, exertional dyspnea, and hypoxia. The
      evaluation did not reveal an acute cardiopulmonary etiology, but FoCUS
      demonstrated a pericardial effusion, with several signs consistent with
      tamponade. The IVC, however, was not distended. She was believed to be
      hypovolemic, but fluid therapy provided minimal benefit. The patient's condition
      improved only after aspiration of the effusion. The patient's presentation was
      likely a "low-pressure" pericardial tamponade. Patients with this subset of
      tamponade often do not have significant venous congestion, but urgent pericardial
      aspiration is still indicated. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: Pericardial tamponade may not manifest with IVC plethora on ultrasound.
      Patients with low-pressure tamponade do not present with the most florid signs of
      tamponade, but they nonetheless fulfill diagnostic criteria for tamponade. If a
      non-plethoric IVC is used to rule out tamponade, the clinician risks delaying
      comprehensive echocardiography or other tests. Furthermore, the potential for
      deterioration to frank shock could be discounted, with inappropriate disposition
      and monitoring.

PMID- 27884578
TI  - Frequent Emergency Department Users with Human Immunodeficiency Virus Infection.

PMID- 27884579
TI  - Number of daily antihypertensive drugs and the risk of osteoporotic fractures in
      older hypertensive adults: National health insurance service - Senior cohort.
AB  - BACKGROUND: Antihypertensive medication represents one of the most common
      prescriptions for senior individuals. Numerous studies have assessed the
      influence of antihypertensive treatment on the risk for osteoporotic fracture,
      yet much controversy remains. We analyzed the relationship between the incidence
      of osteoporotic fracture and the average number of daily antihypertensive drugs
      (NDAD) included in the prescription of elderly hypertensive patients. METHODS:
      The study population was derived from the National Health Insurance Service
      Senior Cohort (2002-2013), and consisted of elderly patients (>=60 years)
      diagnosed with hypertension in 2009, who did not have osteoporotic fractures in
      2008, and underwent at least one national health check-up between 2009 and 2013,
      and had complete records after 2010. The outcome measured was the incidence of
      osteoporotic fractures between 2010 and 2013. The study population was stratified
      into the three groups (low, moderate, and high), in terms of NDAD. RESULTS: A
      total of 137,304 hypertensive patients were included. A multivariate model
      corrected by age, gender, body mass index, systolic blood pressure, underlying
      disease, smoking status, and use of medicines showed that the groups with
      moderate and high NDAD exhibited, respectively, 12% and 16% lower risk of
      osteoporotic fracture compared to that in the group with low NDAD. In terms of
      the risk of osteoporotic fracture associated with the number of daily thiazide
      diuretics (NDTD), the adjusted odds ratios (aOR; 95%CI) were 0.89 (0.84-0.94) and
      0.93 (0.84-1.02) in the groups with moderate and high NDTD, respectively compared
      to low NDTD as reference. As to NDADnotTD, the aOR (95%CI) were 0.90 (95%CI, 0.86
      0.94) and 0.89 (95%CI, 0.84-0.95) in the groups with moderate and high NDADnotTD,
      respectively compared to low NDADnotTD as reference. CONCLUSION: In elderly
      hypertensive patients, the incidence of osteoporotic fracture decreased as the
      NDAD increased. The incidence rate of osteoporotic fracture also decreased with
      the increase in the number of daily non-thiazide antihypertensive drugs.

PMID- 27884580
TI  - A benzimidazole derivative (RCB20) in vitro induces an activation of energetic
      pathways on Taenia crassiceps (ORF strain) cysticerci.
AB  - Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an
      useful experimental model for cysticercosis studies. Benzimidazole derivatives
      are important antihelminthic drugs widely used against helminths. A novel
      compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-benzimidazole (RCB20)
      is a benzimidazole derivative less polar and more lipophilic. The aim of this
      study was to detect the effect of the RCB20 on the in vitro energetic metabolism
      of T. crassiceps cysticerci. For this, products of the metabolism both produced
      and secreted/excreted (S/E) by the parasite were detected through
      spectrophotometry and high performance liquid chromatography after exposure to
      6.5 and 13 MUM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual
      increase in the concentrations of glucose not uptaken by parasites exposed to
      both concentrations RCB20 and ABZSO. There was a higher concentration of all the
      organic acids related to the tricarboxilic acid cycle int the parasites exposed
      to RCB20. The structural differences between RCB20 and ABZSO result in different
      targets within the parasite and in a greater induction of the energetic pathways,
      such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a
      substitute for anthelminthic benzimidazoles due to a differentiated site of
      action with similar outcome.

PMID- 27884581
TI  - Family Stress in Pediatric Critical Care.
AB  - This mixed methods study explored stress in families whose children were
      hospitalized in the pediatric intensive care unit (PICU) for more than one week.
      The study aim was to describe sources of stress for families whose children
      require extended hospitalization in the PICU. Data collection included semi
      structured interviews and completion of the Family Inventory of Life Events and
      Family System Stressor Strength Inventory. Themes reported in this paper are
      separation, not knowing, and the child's illness and distress. Additional
      research is needed to validate these findings in families of other cultures and
      structures, and in other PICUs.

PMID- 27884582
TI  - Education in resuscitation: The need for a new teaching method.

PMID- 27884583
TI  - Impact of an emergency medicine pharmacist on time to thrombolysis in acute
      ischemic stroke: strength of association.

PMID- 27884584
TI  - Early death after emergency department discharge in patients with psychiatric
      illness.

PMID- 27884585
TI  - The successful treatment of 5-fluorouracil (5-FU) overdose in a patient with
      malignancy and HIV/AIDS with uridine triacetate.
AB  - According to the NIH, about 275000 patients receive treatment with 5-Fluorouracil
      (5-FU) and more than 1300 die from 5-FU toxicity every year from life-threatening
      myelosuppression, gastrointestinal complications, and neurotoxicity.
      Immunocompromised persons are at higher risk of developing toxicity. Recently
      uridine triacetate (Vistagard(r)) has been approved by the Food and Drug
      Administration (FDA) as the only specific antidote available for 5-FU poisoning.
      In a clinical trial (n=135), 96% of patients with 5-FU toxicity recovered after
      treatment, where as in a historical control group only 10% survived. This is the
      first published case report of survival after 5-FU overdose who also was
      immunocompromised from HIV/AIDs. A 52year old male with history of HIV/AIDS (CD4
      70), CNS toxoplasmosis and anal cancer presented to the emergency department
      after realizing he had received an entire course of 5-FU in 24 instead of 96h.
      Treatment with uridine triacetate was arranged in the emergency department. After
      receiving treatment the patient was asymptomatic and had an uncomplicated
      hospital course. 5-FU poisoning must be recognized early as uridine triacetate is
      approved by the FDA for use within 96h following the end of 5-FU administration.
      Emergency medicine physicians should promptly recognize and treat 5-FU poisoning.
      However, this may be challenging as patients may not seek medical attention until
      many hours or several days after last administration since symptoms are often
      delayed with 5-FU poisoning.

PMID- 27884587
TI  - Butyrate pretreatment attenuates heart depression in a mice model of endotoxin
      induced sepsis via anti-inflammation and anti-oxidation.
AB  - OBJECTIVES: The depressed heart function is the main complication to cause death
      of septic patients in clinic. It is urgent to find effective interventions for
      this intractable disease. In this study, we investigated whether butyrate could
      be protective for heart against sepsis and the underlying mechanism. METHODS:
      Mice were randomly divided into three groups. Model group challenged with LPS (30
      mg/kg, i.p.) only. Butyrate group received butyrate (200 mg/kg.d) for 3days prior
      to LPS administration (30 mg/kg). Normal group received saline only. 6h and 12h
      after LPS administration were chosen for detection the parameters to estimate the
      effects or mechanism of butyrate pretreatment on heart of sepsis. RESULTS: The
      data showed that septic heart depression was attenuated by butyrate pretreatment
      through improvement of heart function depression (P<0.01) and reduction of
      morphological changes of myocardium. The overexpression of proinflammatory
      factors, TNF-alpha, IL-6 and LTB4, in heart tissues induced by sepsis was
      significantly alleviated by butyrate pretreatment (P<0.01). As oxidative stress
      indicators, SOD and CAT activity, and MDA content in heart were deteriorated by
      LPS challenge, which was noticeably ameliorated by butyrate pretreatment (P<0.01
      or P<0.05). CONCLUSIONS: In conclusion, pretreatment with butyrate attenuated
      septic heart depression via anti-inflammation and anti-oxidation.

PMID- 27884586
TI  - The X factor: Lack of bleeding after an acute apixaban overdose.
AB  - We present an acute apixaban overdose without reported coingestants; it is the
      first such case report associated with multiple serum drug levels to assist in
      determining overdose kinetics. A 62 year old female presented to an emergency
      department (ED) 2 hours after ingesting sixty 5 mg tablets (5mg/kg) of her
      spouse's apixaban medication. She denied coingestants, and did not take her
      prescribed medications that day. Her vital signs were normal and she denied
      symptoms. Chemistry and hematology labs were unremarkable. Plasma apixaban
      concentrations were 2765.6 ng/ml at 14 hours post ingestion with a non-linear
      half life. There was no utilization of blood products or factor replacement.
      There was never any bleeding, and her hemoglobin did not decrease. This case
      demonstrates that a single ingestion of apixaban can occur without any
      complications occurring.

PMID- 27884588
TI  - Colour preference between adults and children during a dental treatment session.
AB  - BACKGROUND: It is evidently shown that colour has physical, psychological and
      sociological effects on human beings. There are many studies showing the effects
      of colours on brain activity. Colour preferences may change from childhood to
      adulthood and are significantly different in various age groups. The aim of this
      study was to evaluate the adults and children in their preference for mouthrinses
      in various colours under stress condition during a dental treatment session.
      METHODS: 240 adults and 263 children were included in the study. Three
      transparent cups were filled with water, two of which were coloured green/pink
      rinsing by dissolving a tablet in the water. Cups were placed near the dental
      unit. During dental treatment sessions, patients were told to rinse their mouth
      with whichever cup they preferred. Preferred colour of cup, gender and age of
      patient, number of sessions were recorded. Data were statistically analysed by
      SPSS 15.0 programme and chi-square tests. RESULTS: Half of all cases preferred
      water. In adults, while females statistically significantly preferred water,
      males chose cups with coloured contents (p<0.01). Male adults preferred more than
      one rinsing solution in a dental treatment session. Children mostly preferred
      water. Even if adults preferred cups with coloured contents in multi-dental
      treatment sessions, children regularly preferred water (p<0.001). Female and male
      children mostly preferred water as a rinsing solution. Water was the most often
      choice for all patients. Both patients' gender and colours of cups affected
      choices made by adults and children. CONCLUSIONS: Female adults and children were
      not interested in trying colourful mouthrinses, while male adults were curious
      about trying colourful mouthrinses during dental treatment sessions under stress
      condition.

PMID- 27884589
TI  - Cohabitation with an Ehrlich tumor-bearing cagemate induces immune but not
      behavioral changes in male mice.
AB  - Cohabitation with Ehrlich ascitic tumor-injected conspecifics induces behavioral,
      neurochemical, endocrine and immune changes indicative of stress and immune
      impairment in female mice. The present work analyzed the effects of similar
      cohabitation in Swiss and Balb/C male mice. At least 12 pairs of male mice were
      divided into a control group and an experimental group. On experimental day 1
      (ED1), one animal within each experimental pair was inoculated with 5*106 Ehrlich
      tumor cells intraperitoneally (i.p.); the other animal was kept undisturbed and
      was referred to as the CSP (companion of a sick partner). One male mouse of each
      control pair was treated i.p. with 0.9% NaCl (1mL/kg); the other animal (the CHP,
      companion of a healthy partner) was kept undisturbed. Cohabitation with a sick
      partner for 11days did not induce any behavioral, hypothalamic noradrenergic,
      corticosterone or adrenal weight changes in the Swiss CSP male mice compared to
      those of the Swiss CHP group. However, impairments in neutrophil phagocytosis and
      oxidative burst as well as increased levels of catecholamines were observed in
      Swiss and Balb/C CSP mice relative to CHP male animals of the same strains on
      ED11 and ED14, respectively. Moreover, after a challenge with 5*106 Ehrlich tumor
      cells on ED11 of cohabitation, the number and concentration of tumor cells found
      in the ascitic fluid were higher in the Swiss CSP male mice than in the CHP mice.
      These data suggest that the immune changes observed in Swiss and Balb/C male CSP
      mice after cohabitation with a sick cagemate might, ultimately, depend on the
      changes induced by catecholamines, as previously reported for CSP female mice.
      However, contrary to that reported in Swiss CSP female mice, changes in
      behavioral and hypothalamic noradrenaline activity were not found in the Swiss
      CSP male mice analyzed in this work. This fact suggests that male and female CSP
      mice might use similar immune but different CNS strategies against the threats
      posed by the tumor-bearing animals.

PMID- 27884591
TI  - Toll-like receptor ligands induce cytokine and chemokine production in human
      inner ear endolymphatic sac fibroblasts.
AB  - OBJECTIVE: Against recent reports concerning cytokine or chemokine in mouse or
      rat inner ear cells, it is almost unknown whether human inner ear cells would
      produce cytokine or chemokine. We have for the first time established the human
      inner-ear-derived fibroblasts from endolymphatic sac. METHODS: The expression
      levels of Toll-like receptors (TLRs) in human endolymphatic sac fibroblasts, and
      the effect on cytokine or chemokine production of the TLR ligands have been
      examined. To demonstrate the intracellular pathways involved in the regulation of
      cytokine-production, we used specific inhibitors of c-Jun N-terminal kinase
      (JNK), extracellular signal-related kinase (ERK), p38 mitogen-activated protein
      kinase (p38 MAPK)-signaling and N-acetyl-l-cysteine (NAC). RESULTS: TLR 2, 3, 4
      and 9 were highly expressed in human endolymphatic sac fibroblasts. The TLR 3
      ligand, polyinosinic-polycytidylic acid (poly(I:C)) significantly enhanced the
      secretion of thymic stromal lymphopoietin (TSLP), B lymphocyte stimulator (BLyS),
      IFNgamma-inducible protein 10 (IP-10), and macrophage inflammatory protein 1
      alpha (MIP-1alpha) from the cells. The inhibitor of JNK strongly reduced the
      poly(I:C)-induced TSLP-production. The antioxidant drug, NAC also reduced the
      TSLP-production in fibroblasts stimulated with poly(I:C). CONCLUSION: Our
      findings suggest human inner-ear-endolymphatic sac derived fibroblasts can
      produce the cytokine and chemokine in response to TLR ligands and play a certain
      role during the initiation of an immune response.

PMID- 27884590
TI  - Physical activity induced protection against breast cancer risk associated with
      delayed parity.
AB  - Epidemiological evidence indicates that physical activity between menarche and
      first pregnancy is associated with a lower risk of breast cancer among women with
      at least 20years between these reproductive events. The mechanism by which
      physical activity during this interval confers protection is unknown. This study
      used a novel animal model to assess potentially protective effects of physical
      activity on tumor development in delayed parity. Thirty-six female Sprague Dawley
      rats received an i.p. injection of 50mg/kg N-methyl-N-nitrosourea (MNU) at 5weeks
      of age. Estrogen and progesterone pellets were implanted subcutaneously 1week
      (early parity, EP, n=8) or 4weeks (delayed parity, DP, n=11) following MNU
      injection. An additional group of DP rats were progressively exercise trained
      (Ex+DP, n=9) on a treadmill following MNU injection for 7weeks (up to 20m/min at
      15% incline for 30min). We observed the greatest tumor latency and smallest tumor
      burden in Ex+DP animals. Ductal hyperplasia and inflammation of non-tumor bearing
      mammary glands were only found in DP, and we detected a significant increase in
      collagen for DP and Ex+DP compared to EP. Exercise induced differential gene
      expression of cyclin-dependent kinase-inhibitor 1C (Cdkn1c) and urokinase
      plasminogen activator (Plau) in mammary tissue of Ex+DP animals compared to DP
      alone. While there are delayed parity-induced changes in mammary gland collagen
      and gene expression levels, Ex+DP animals had longer tumor latency, smaller tumor
      burden, and glandular tissue resistant to ductal hyperplasia. Exercise may induce
      protection through beneficial regulation of gene expression profiles.

PMID- 27884592
TI  - Nasopharyngeal carcinoma with mastoid recurrence after concurrent
      chemoradiotherapy masquerading as acute otomastoiditis.
AB  - Nasopharyngeal cancer (NPC) with mastoid recurrence is extraordinarily rare, and
      its development is thought to involve the Eustachian tube. We herein report a
      case of NPC with mastoid recurrence masquerading as acute otomastoiditis with
      facial paralysis in a 60-year-old man 44 months after concurrent
      chemoradiotherapy. The diagnosis was confirmed by exploratory
      tympanomastoidectomy with biopsy and Epstein-Barr-encoding region (EBER) in situ
      hybridization. Distant liver metastasis was detected simultaneously, and the
      patient underwent salvage treatment. He died 15 months later. Despite the rarity
      of mastoid recurrence, clinicians should be vigilant in the differential
      diagnosis of mastoiditis in patients with NPC after radiotherapy. Tumor biopsy
      and EBER in situ hybridization can aid in the accurate diagnosis of this uncommon
      condition.

PMID- 27884593
TI  - Idiopathic interstitial pneumonia-associated pulmonary hypertension: A target for
      therapy?
AB  - Advances in the treatment of idiopathic interstitial pneumonia (IIP) represent an
      urgent, unmet medical need for patients with this category of diffuse parenchymal
      lung disease. IIPs involve varying combinations of fibrosis and inflammation of
      unknown cause and may be associated with pulmonary hypertension (PH). When it
      occurs, PH is associated with higher oxygen needs, greater functional impairment,
      and increased mortality. However, whether or when PH is a maladaptive versus
      adaptive phenomenon remains to be determined. Despite their differing prognoses,
      it does appear that the IIPs may follow a similar course once PH supervenes.
      Therefore, it may be worthwhile to explore studies of PH medications in IIP as a
      group rather than as individual entities. Such a broad approach eliminates the
      need to nuance specific diagnoses and thereby facilitates study recruitment and
      broadens the applicability of the results.

PMID- 27884594
TI  - Surface properties of polyene glycol phospholipid monolayers.
AB  - We studied the surface properties of monolayers composed of polyunsaturated
      conjugated ethylene glycol phospholipids (carotenoid lipids), compared the data
      with monolayers of dipalmitoylphosphatidylcholine (DPPC) to which carotenoids
      were added and evaluated the impact of the unsaturated glycol lipids on
      monolayers with the glycerolipid DPPC. The carotenoid based glycol lipids formed
      monolayers at the air/water interface. Using the Langmuir method we obtained
      series of pressure-area (pi-A) isotherms and determined the limiting area A per
      molecule of three glycol lipids, C30:9-C0A=42.6+/-1.4A2, C30:9-C2A=76.1+/-2.5A2
      and C30:9-C12A=354.0+/-12.0A2 and their mixtures with DPPC at various mole
      fraction X. C30:9-C0 and C30:9-C2 did not affect significantly the shape of the
      isotherm, but caused their slight shift toward a lower and larger molecular area,
      respectively. C30:9-C12 at mole fractions X>0.02 affected the shape of isotherm.
      The compressibility modulus Cs-1 of monolayers depended on the surface pressure.
      Cs-1 value was substantially higher for DPPC monolayers in comparison with those
      of pure glycol lipids. At low surface pressure pi=5-10mN/m and low mole fractions
      X<0.02 the glycol lipids formed complexes with DPPC; at higher surface pressure
      the separation of pure components took place. The dipole potential of the
      monolayers composed of cationic glycol lipids C30:9-C2 and C30:9-C12 was higher
      in comparison with those of zwitterionic DPPC and C30:9-C0. This may be connected
      with various contributions of dipole moments of the molecules and their
      orientation in the monolayer.

PMID- 27884595
TI  - Melatonin: Protection against age-related cardiac pathology.
AB  - Aging is a complex and progressive process that involves physiological and
      metabolic deterioration in every organ and system. Cardiovascular diseases are
      one of the most common causes of mortality and morbidity among elderly subjects
      worldwide. Most age-related cardiovascular disorders can be influenced by
      modifiable behaviours such as a healthy diet rich in fruit and vegetables,
      avoidance of smoking, increased physical activity and reduced stress. The role of
      diet in prevention of various disorders is a well-established factor, which has
      an even more important role in the geriatric population. Melatonin, an
      indoleamine with multiple actions including antioxidant properties, has been
      identified in a very large number of plant species, including edible plant
      products and medical herbs. Among products where melatonin has been identified
      include wine, olive oil, tomato, beer, and others. Interestingly, consumed
      melatonin in plant foods or melatonin supplementation may promote health benefits
      by virtue of its multiple properties and it may counteract pathological
      conditions also related to cardiovascular disorders, carcinogenesis, neurological
      diseases and aging. In the present review, we summarized melatonin effects
      against age-related cardiac alterations and abnormalities with a special focus on
      heart ischemia/reperfusion (IR) injury and myocardial infarction.

PMID- 27884596
TI  - Altered corticosterone levels and social play behavior after prolonged maternal
      separation in adolescent male but not female Wistar rats.
AB  - Early-life socio-environmental factors are crucial for normal developmental
      processes; adverse experiences early in life can therefore lead to detrimental
      effects in several physiological systems. The aim of this study was to examine
      short-term effects of early adverse experiences in a maternal separation (MS)
      rodent model. In this study two separation conditions were used: daily 15- (MS15)
      or 360-min (MS360) separation of the litter from the dam during postnatal day 1
      21. In early adolescence, male and female offspring were subjected to a single
      isolation procedure with analysis of corticosterone levels prior to and after
      isolation. In addition, social play behavior was assessed during mid-adolescence.
      There was a clear difference between male and female offspring in both tests
      performed. There was no difference in corticosterone levels between the female MS
      groups, whereas MS360 males showed higher baseline and recovery corticosterone
      levels than MS15 males. The amount of pinning, a specific social play behavior,
      was affected by rearing with MS360 males having a higher frequency than MS15
      males, while there was no difference between the female MS groups. The
      observation that males but not females are affected by MS360 has previously been
      reported for adult animals, and herein we show that this difference is present
      already in adolescence. Changes in corticosterone levels and social behavior
      following early-life adversity have been associated with adult behavioral
      alterations, and our results confirm that these changes emerge already within
      adolescence.

PMID- 27884597
TI  - Prediction of Competing Mortality for Decision-making Between Surgery or
      Observation in Elderly Patients With T1 Kidney Cancer.
AB  - OBJECTIVE: To predict the risk of cancer-specific mortality (CSM) or other-cause
      mortality (OCM) for T1 kidney cancer patients, aiming at identifying those who
      would benefit from surgery over observation. PATIENTS AND METHODS: Overall,
      11,192 T1 kidney cancer patients treated with surgery or observation in the
      Surveillance, Epidemiology, and End Results-Medicare database were assessed. A
      competing risk regression (CRR) model was fitted to predict CSM and OCM after
      surgery or observation. Covariates consisted of age, gender, race, Charlson
      comorbidity index (CCI), history of acute kidney injury or chronic kidney
      disease, tumor size, and year of diagnosis. RESULTS: At a median follow-up of 64
      months, the 5-year rates of CSM and OCM were 6.7% and 24%, respectively. At CRR
      predicting CSM, surgery (hazard ratio [HR] 0.46; P < .0001) and year of diagnosis
      (HR 0.96; P < .0001) were associated with lower CSM risk. Conversely, age (HR
      1.05; P < .0001), CCI (HR 1.07; P < .0001), and tumor size (HR 1.03; P < .0001)
      were associated with higher CSM risk. At CRR predicting OCM, surgery (HR 0.66; P
      < .0001), female gender (HR 0.83; P < .0001), Other race (HR 0.82; P < .0001),
      and year of diagnosis (HR 0.95; P < .0001) were associated with lower OCM risk.
      Conversely, age (HR 1.06; P < .0001), African American race (HR 1.16; P < .01),
      CCI (HR 1.17; P < .0001), and acute kidney injury or chronic kidney disease (HR
      1.35; P < .0001) were associated with higher OCM risk. CONCLUSION: The benefit of
      surgery over observation was more pronounced in younger and healthier patients
      with larger tumors. The proposed model can aid in clinical decision-making,
      providing crucial information on CSM and OCM risk after either treatment
      modality.

PMID- 27884598
TI  - Coiled Coils - A Model System for the 21st Century.
AB  - alpha-Helical coiled coils were described more than 60 years ago as simple,
      repetitive structures mediating oligomerization and mechanical stability. Over
      the past 20 years, however, they have emerged as one of the most diverse protein
      folds in nature, enabling many biological functions beyond mechanical rigidity,
      such as membrane fusion, signal transduction, and solute transport. Despite this
      great diversity, their structures can be described by parametric equations,
      making them uniquely suited for rational protein design. Far from having been
      exhausted as a source of structural insight and a basis for functional
      engineering, coiled coils are poised to become even more important for protein
      science in the coming decades.

PMID- 27884599
TI  - Influence of sequence and lipid type on membrane perturbation by human and rat
      amyloid beta-peptide (1-42).
AB  - The hallmark characteristics of plaque formation and neuronal cell death in
      Alzheimer's disease (AD) are caused principally by the amyloid beta-peptide
      (Abeta). Abeta sequence and lipid composition are essential variables to consider
      when elucidating the impact of biological membranes on Abeta structure and the
      effect of Abeta on membrane integrity. Atomistic molecular dynamics simulations
      testing two Abeta sequences, human and rat Abeta (HAbeta and RAbeta,
      respectively), and five lipid types were performed to assess the effect of these
      variables on membrane perturbation and potential link to AD phenotype differences
      based on differences in sequence. All metrics agree insomuch that monomeric
      HAbeta and RAbeta contribute to membrane perturbation by causing a more rigid,
      gel-like lipid phase. Differences between HAbeta and RAbeta binding on degree of
      membrane perturbation were based on lipid headgroup properties. Cholesterol was
      found to moderate the amount of perturbation caused by HAbeta and RAbeta in a
      model raft membrane. The difference in position of an arginine residue between
      HAbeta and RAbeta influenced peptide-membrane interactions and was determined to
      be the mediating factor in observed differences in lipid affinity and degree of
      membrane disruption. Overall, this work increases our understanding of the
      influence of sequence and lipid type on Abeta-membrane interactions and their
      relationship to AD.

PMID- 27884601
TI  - Evaluating small-airways disease in asthmatic patients: The utility of
      quantitative computed tomography.

PMID- 27884600
TI  - Six-transmembrane epithelial antigens of the prostate comprise a novel
      inflammatory nexus in patients with pustular skin disorders.
AB  - BACKGROUND: Pustular skin disorders are a category of difficult-to-treat and
      potentially life-threatening conditions that involve the appearance of neutrophil
      rich pustules. The molecular basis of most pustular skin conditions has remained
      unknown. OBJECTIVE: We sought to investigate the molecular basis of 3 pustular
      skin disorders: generalized pustular psoriasis (GPP), palmoplantar pustulosis
      (PPP), and acute generalized exanthematous pustulosis (AGEP). METHODS: Microarray
      analyses were performed to profile genome-wide gene expression of skin biopsy
      specimens obtained from patients with GPP, PPP, or AGEP and healthy control
      subjects. Functional enrichment, gene network, and k-means clustering analyses
      were used to identify molecular pathways dysregulated in patients with these
      disorders. Immunohistochemistry and immunofluorescence were used to determine
      protein localization. Quantitative RT-PCR and ELISA were used to determine
      transcript and secreted cytokine levels. Small interfering RNA was used to
      decrease transcript levels. RESULTS: Molecules and pathways related to neutrophil
      chemotaxis emerged as common alterations in patients with GPP, PPP, and AGEP,
      which is consistent with the pustular phenotypes. Expression of two 6
      transmembrane epithelial antigens of the prostate (STEAP) proteins, STEAP1 and
      STEAP4, was increased in patients' skin and colocalized with IL-36gamma around
      neutrophilic pustules. STEAP1/4 expression clustered with and positively
      correlated with that of IL-1, the IL-36 family proteins, and CXCL1/8. STEAP4
      expression was activated by cytokines and suppressed by inhibition of mitogen
      activated protein kinase kinase 1/2, whereas STEAP1 expression appeared less
      prone to such dynamic regulation. Importantly, STEAP1/4 knockdown resulted in
      impaired induction of a broad spectrum of proinflammatory cytokines, including IL
      1, IL-36, and the neutrophil chemotaxins CXCL1 and CXCL8. STEAP1/4 knockdown also
      reduced the ability of keratinocytes to induce neutrophil chemotaxis. CONCLUSION:
      Transcriptomic changes in 3 pustular skin disorders, GPP, PPP, and AGEP,
      converged on neutrophil chemotaxis and diapedesis and cytokines known to drive
      neutrophil-rich inflammatory processes, including IL-1 and members of the IL-36
      family. STEAP1 and STEAP4 positively regulate the induction of proinflammatory
      neutrophil-activating cytokines.

PMID- 27884603
TI  - Cranial nerve involvement in Charcot-Marie-Tooth Disease.
AB  - BACKGROUND: Charcot-Marie-Tooth Disease (CMT) is a rare disorder with less than
      200,000 cases reported in the US every year, making diagnosis challenging. MR and
      CT imaging has become more common in the evaluation of CMT to identify areas of
      disease involvement. CASE REPORT: A 27-year-old female from Guatemala with a past
      history of polio initially presented to the emergency room for necrotizing
      pneumonia. MRI images demonstrated smoothly enlarged, mildly enhancing trigeminal
      nerves. CT showed bony widening of the skull base foramina. The patient was noted
      to have atrophy and weakness of her extremities with decreased sensation, distal
      more than proximal, and pes cavus. An electromyogram demonstrated absent response
      in the right median, ulnar, peroneal, and tibial motor studies and bilateral
      radial and right sural sensory studies. MRI of the spine demonstrated smooth,
      symmetric enlargement and mild enhancement of the distal spinal nerve roots and
      cauda equine. DISCUSSION: CMT is a group of disorders with a wide range of
      clinical presentations and abnormalities. Cranial nerve involvement is
      infrequently described in CMT 1A. In our case and prior studies, there does not
      appear to be a correlation between cranial nerve involvement and symptoms.
      Trigeminal neuralgia has been described in patients in CMT, but is not common and
      was not seen in our patient despite abnormal trigeminal nerve findings on
      imaging. Our patient also demonstrated involvement of the facial nerve without
      facial muscle weakness. Clinical features are key in distinguishing CMT 1A from
      other forms of HMSN.

PMID- 27884602
TI  - A data-driven weighting scheme for multivariate phenotypic endpoints
      recapitulates zebrafish developmental cascades.
AB  - Zebrafish have become a key alternative model for studying health effects of
      environmental stressors, partly due to their genetic similarity to humans, fast
      generation time, and the efficiency of generating high-dimensional systematic
      data. Studies aiming to characterize adverse health effects in zebrafish
      typically include several phenotypic measurements (endpoints). While there is a
      solid biomedical basis for capturing a comprehensive set of endpoints, making
      summary judgments regarding health effects requires thoughtful integration across
      endpoints. Here, we introduce a Bayesian method to quantify the informativeness
      of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi
      endpoint summary measure, called weighted Aggregate Entropy (wAggE). We implement
      wAggE using high-throughput screening (HTS) data from zebrafish exposed to five
      concentrations of all 1060 ToxCast chemicals. Our results show that our empirical
      weighting scheme provides better performance in terms of the Receiver Operating
      Characteristic (ROC) curve for identifying significant morphological effects and
      improves robustness over traditional curve-fitting approaches. From a biological
      perspective, our results suggest that developmental cascade effects triggered by
      chemical exposure can be recapitulated by analyzing the relationships among
      endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate
      phenotypes that can reveal underlying etiological processes.

PMID- 27884604
TI  - Surgical management of falcine meningiomas: Experience of 95 patients.
AB  - Falcine meningiomas, defined as a meningiomas arising from the falx not involving
      the superior sagittal sinus, account for 9% of all intracranial meningiomas. We
      analyzed 95 patients with falcine meningiomas who underwent surgical removal of
      their lesion at our institution between 2001 and 2014. Surgical management of
      these patients, focusing on anatomical and clinical features is described. Thus,
      based on our series, a surgical algorithm, classifying the falcine meningioma
      into four types, according to location at the falx, and using an ipsilateral
      interhemispheric approach in supine or prone position, is described. The median
      length of follow-up was 7.1years (range 1.6-12.3years). Approximately one-third
      of all patients was asymptomatic, headaches occurred in 27 patients, seizures in
      14 cases, and lower-extremity weakness in 9 cases. In this series, the middle
      third of the falx was the most frequently involved site (55,78%), while the
      anterior third (26,31%) and the posterior type (17,89%) were less common. The
      transitional and meningothelial types occurred in 69 of patients and a high grade
      in only two patients. Compared with previous series in literature, there was no
      mortality and Gross Total Resection was obtained in 83 (87,5%) cases. Three of 95
      patients experienced new or worsened neurological deficits after surgery while
      other complications were relatively in only 6 cases. This study presents our good
      results about removal of the tumor while preserving major cortical veins and the
      sinus using advanced microsurgical tools.

PMID- 27884608
TI  - Response to the Letter to the Editor by Yang et al.

PMID- 27884606
TI  - BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein
      70 (Hsp70) to the Small Heat Shock Proteins.
AB  - Small heat shock proteins (sHsps) are a family of ATP-independent molecular
      chaperones that are important for binding and stabilizing unfolded proteins. In
      this task, the sHsps have been proposed to coordinate with ATP-dependent
      chaperones, including heat shock protein 70 (Hsp70). However, it is not yet clear
      how these two important components of the chaperone network are linked. We report
      that the Hsp70 co-chaperone, BAG3, is a modular, scaffolding factor to bring
      together sHsps and Hsp70s. Using domain deletions and point mutations, we found
      that BAG3 uses both of its IPV motifs to interact with sHsps, including Hsp27
      (HspB1), alphaB-crystallin (HspB5), Hsp22 (HspB8), and Hsp20 (HspB6). BAG3 does
      not appear to be a passive scaffolding factor; rather, its binding promoted de
      oligomerization of Hsp27, likely by competing for the self-interactions that
      normally stabilize large oligomers. BAG3 bound to Hsp70 at the same time as
      Hsp22, Hsp27, or alphaB-crystallin, suggesting that it might physically bring the
      chaperone families together into a complex. Indeed, addition of BAG3 coordinated
      the ability of Hsp22 and Hsp70 to refold denatured luciferase in vitro. Together,
      these results suggest that BAG3 physically and functionally links Hsp70 and
      sHsps.

PMID- 27884607
TI  - Management of Massive Hemoptysis After Pulmonary Thromboembolectomy Using a
      Double Bronchial Blocker System.

PMID- 27884605
TI  - Arsenic-Induced Activation of the Homeodomain-Interacting Protein Kinase 2
      (HIPK2) to cAMP-Response Element Binding Protein (CREB) Axis.
AB  - Cyclic AMP-response element-binding protein (CREB) plays key transcriptional
      roles in cell metabolism, proliferation, and survival. Ser133 phosphorylation by
      protein kinase A (PKA) is a well-characterized CREB activation mechanism.
      Homeodomain-interacting protein kinase (HIPK) 2, a nuclear serine/threonine
      kinase, activates CREB through Ser271 phosphorylation; however, the regulatory
      mechanism remains uncharacterized. Transfection of CREB in HEK293 cells together
      with the kinase demonstrated that HIPK2 phosphorylated CREB at Ser271 but not
      Ser133; likewise, PKA phosphorylated CREB at Ser133 but not Ser271, suggesting
      two distinct CREB regulatory mechanisms by HIPK2 and PKA. In vitro kinase assay
      revealed that HIPK2, and HIPK1 and HIPK3, directly phosphorylated CREB. Cells
      exposed to 10MUM sodium arsenite increased the stability of HIPK1 and HIPK2
      proteins, leading to CREB activation via Ser271 phosphorylation. Phospho-Ser271
      CREB showed facilitated interaction with the TFIID subunit coactivator TAF4
      assessed by immunoprecipitation. Furthermore, a focused gene array between cells
      transfected with CREB alone and CREB plus HIPK2 over empty vector-transfected
      control displayed 14- and 32-fold upregulation of cyclin A1, respectively, while
      no upregulation was displayed by HIPK2 alone. These results suggest that the
      HIPK2-phospho-Ser271 CREB axis is a new arsenic-responsive CREB activation
      mechanism in parallel with the PKA-phospho-Ser133 CREB axis.

PMID- 27884609
TI  - Tricuspid Annular Plane Systolic Excursion: Comparing Transthoracic to
      Transesophageal Echocardiography.
AB  - OBJECTIVE: Tricuspid annular plane systolic excursion (TAPSE) represents movement
      of the lateral annulus of the tricuspid valve toward the apex and denotes right
      ventricular contractility in the long axis. In transesophageal echocardiography
      with the probe in the mid-esophagus, TAPSE occurs at a significant angle to the M
      mode scan line. The authors describe a novel method to assess TAPSE in 2
      dimensions (2D) and compare this with an established method. DESIGN: Prospective
      cohort study. SETTING: Tertiary cardiac unit. PARTICIPANTS: Forty-three patients
      scheduled for outpatient transesophageal echocardiography. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: TAPSE was assessed from the transthoracic apical
      window using M-mode (M-TAPSE) and the mid-esophageal 4-chamber view (2D-TAPSE).
      To assess 2D-TAPSE, the authors placed an annotation arrow at the junction of the
      tricuspid annulus and right ventricular free wall during diastole, and a second
      arrow at this junction at end-systole; 2D-TAPSE represented the distance between
      the arrows. The mean M-TAPSE was 20.5 (5.9) mm and 2D-TAPSE was 20.5 (5.8) mm.
      The mean angle between the direction of the lateral tricuspid annular motion and
      the M-mode scan line from the transthoracic apical window was 19.4 (7.6) degrees
      and from the mid-esophageal 4-chamber view 62.6 (15.7) degrees (p<0.001). There
      was a close correlation between M-TAPSE and 2D-TAPSE; r2 = 0.93. Ninety-five
      percent of 2D-TAPSE were -3.2mm to+3.1mm of M-TAPSE (95% confidence interval -4.0
      mm to+4.0 mm). The positive predictive value of 2D-TAPSE<17 mm to predict M
      TAPSE<17 was 83%. The negative predictive value of 2D-TAPSE>=17 mm to predict M
      TAPSE>=17 was 93%. The intra- and inter-observer variability for 2D-TAPSE was
      6.7% and 9.7%, respectively. CONCLUSIONS: Transesophageal 2D-TAPSE appeared to be
      a reliable and simple method to assess right ventricular function, and
      demonstrated a close correlation with transthoracic M-TAPSE.

PMID- 27884610
TI  - Impact of the Direct Oral Anticoagulants on Activated Clotting Time.

PMID- 27884611
TI  - Microglial positron emission tomography (PET) imaging in epilepsy: Applications,
      opportunities and pitfalls.
AB  - Neuroinflammation is increasingly implicated in epileptogenesis and epilepsy.
      Microglia are an important mediator of central nervous system inflammation, and
      the development of positron emission tomography (PET) radioligands which bind the
      Translocator Protein (TSPO), an outer mitochondrial membrane protein expressed by
      microglia, has enabled in vivo measurement of neuroinflammation. Here, we outline
      the principles and potential pitfalls of TSPO PET imaging in relation to
      epilepsy, and opportunities for using TSPO imaging as a biomarker for future anti
      inflammatory based therapeutics in epilepsy.

PMID- 27884612
TI  - Enucleation: A treatment alternative for branch duct intraductal papillary
      mucinous neoplasms.
AB  - BACKGROUND: Small, asymptomatic, branch-duct intraductal papillary mucinous
      neoplasms of the pancreas are often kept under surveillance despite their
      malignant potential. The management of branch-duct intraductal papillary mucinous
      neoplasm is controversial with regard to indications and extent of any operative
      intervention. The present study aimed to evaluate enucleation as an alternative
      operative approach for branch-duct intraductal papillary mucinous neoplasms to
      exclude and prevent malignancy. METHODS: For branch-duct intraductal papillary
      mucinous neoplasms of <30 mm in diameter and an acceptable distance from the main
      pancreatic duct, enucleation was considered as the operative approach of choice.
      All patients scheduled for enucleation of branch-duct intraductal papillary
      mucinous neoplasm on the basis of these features between January 2004 and
      September 2014 were analyzed. Among these, patients with successful enucleation
      were compared with those who were scheduled for enucleation but converted
      intraoperatively to pancreatic resection (intention-to-treat analysis). End
      points were hospital morbidity and mortality as well as histopathology and
      functional outcome at a mean follow-up of 32 months. RESULTS: In the study, 115
      patients with presumed branch-duct intraductal papillary mucinous neoplasm and
      the intention to perform pancreatic enucleation were included; 87 enucleations
      were performed in 74 patients. In 41 patients, enucleation was converted to a
      pancreatic resection (procedure-specific success rate 64%); indications for
      conversion included location or size (46%), presence of multicystic lesions
      (39%), or involvement of the main pancreatic duct (15%). Of the 74 patients with
      enucleation, 64 branch-duct intraductal papillary mucinous neoplasms revealed low
      (85%), 11% moderate dysplasia-, and 4% high-grade dysplasia on histology. Among
      converted resections, 6 intraductal papillary mucinous neoplasms revealed high
      grade dysplasia or invasive carcinoma (15%). Intention-to-treat analysis with
      patients converted to pancreatic resection showed that enucleations resulted in
      less blood loss (100 vs 400 mL) and a shorter operation time (146 vs 255 minutes;
      P < .001 each). Postoperative morbidity including postoperative pancreatic
      fistula was similar in both groups. No mortality occurred after enucleation;
      after formal resection, 1 patient died due to multiorgan failure. Both hospital
      stay (10 vs 14 days) and rates of postoperative endocrine and exocrine
      dysfunction rates were less after enucleation (P < .02 each). Intraductal
      papillary mucinous neoplasm-specific recurrence rates (3% vs 6%) were similar in
      both groups. CONCLUSION: Enucleation is a safe procedure that can be performed
      successfully in a high proportion of branch-duct intraductal papillary mucinous
      neoplasms and should be considered instead of standard resections as an important
      function-preserving alternative. Limitations may occur due to malignancy, size,
      localization, multilocularity, or main-duct involvement requiring conversion to a
      formal, anatomic resection. Beside the advantages in the short-term course,
      functional outcome seems to be superior after enucleation, and intraductal
      papillary mucinous neoplasm-specific recurrence rates are not increased compared
      with standard resections, at least at a mean follow-up of 32 months.

PMID- 27884613
TI  - Appendectomy in patients with human immunodeficiency virus: Not as bad as we once
      thought.
AB  - BACKGROUND: The number of patients living with human immunodeficiency virus and
      acquired immunodeficiency syndrome is growing due to advances in antiretroviral
      therapy. Existing literature on appendectomy within this patient population has
      been limited by small sample sizes. Therefore, we used a large, multiyear,
      nationwide database to study this topic comprehensively. METHODS: Using the
      Nationwide Inpatient Sample, we identified 338,805 patients between 2005 and 2012
      who underwent laparoscopic or open appendectomy for acute appendicitis. Interval
      appendectomies were excluded. We used multivariable adjusted regression models to
      test differences between patients with human immunodeficiency virus without
      acquired immunodeficiency syndrome and a reference group, as well as human
      immunodeficiency virus with acquired immunodeficiency syndrome and a reference
      group, with regard to duration of stay, hospital charges, in-hospital
      complications, and in-hospital mortality. Models were adjusted for patient age,
      sex, race, insurance, socioeconomic status, Elixhauser comorbidity score, and
      appendix perforation. RESULTS: There were 1,291 (0.38%) patients with human
      immunodeficiency virus, among which 497 (0.15%) patients had acquired
      immunodeficiency syndrome. In regression analysis, human immunodeficiency virus
      alone was not associated with adverse outcomes, while acquired immunodeficiency
      syndrome alone was associated with longer duration of stay (incidence rate ratio
      1.40 [1.37-1.57 95% confidence interval], P < .0001), increased total charges
      (exponentiated coefficient 1.16 [1.10-1.23 95% confidence interval], P < .0001),
      and increased risk of postoperative infection (odds ratio 2.12 [1.44-3.13 95%
      confidence interval], P = .0002). CONCLUSION: Patients with acquired
      immunodeficiency syndrome who undergo appendectomy for acute appendicitis are
      subject to longer and more expensive hospital admissions and have greater rates
      of postoperative infections while patients with human immunodeficiency virus
      alone are not at risk for adverse outcomes.

PMID- 27884614
TI  - Robotic major hepatectomy: Is there a learning curve?
AB  - BACKGROUND: Robotic hepatectomy has been suggested as a safe and effective
      management of liver disease. However, no large case series have documented the
      learning curve for robotic major hepatectomy. METHOD: We conducted a
      retrospective study for robotic major hepatectomy performed by the same operative
      team between January 2012 and October 2015 and evaluated the learning curve for
      operation time using the cumulative sum method, presented as cumulative
      sumoperation time. RESULTS: Overall, there were 183 robotic hepatectomies, 92 of
      which were performed in patients who underwent robotic major hepatectomy: left
      hemihepatectomy was performed in 32 (34.8%) patients, right hemihepatectomy in 41
      (44.6%), left trisectionectomy in 3 (3.3%), right trisectionectomy in 6 (6.5%),
      and 8-5-4 trisegmentectomy in 10 (10.8%). The median duration of surgery was 434
      minutes (142-805 minutes) and the median blood loss was 195 mL (50-2,000 mL).
      Fifty-nine percent of patients had malignancies, and those with advanced stages
      of cancer had more blood loss during an operation. The cumulative sumoperation
      time model of robotic major hepatectomy suggested that the learning curve
      comprised 3 characteristic phases: initial (phase 1, 15 patients), intermediate
      (phase 2, 25 patients), and mature (phase 3, 52 patients). The learning effects
      were underlined by shorter operation time and hospital stay after phase 1 and
      less blood loss after phase 2. CONCLUSION: This is the largest series regarding
      robotic major hepatectomy. Our findings suggest that a solid training program
      based on the learning curve should be considered for beginners of robotic
      hepatectomy. Participants should evaluate the evolution of our minimally invasive
      hepatectomy before considering our robotic experience.

PMID- 27884615
TI  - Toxicokinetics of titanium dioxide (TiO2) nanoparticles after inhalation in rats.
AB  - This study focused on the generation of aerosols of titanium dioxide (TiO2)
      nanoparticles (NPs) and their disposition kinetics in rats. Male Sprague-Dawley
      rats were exposed by inhalation to 15mg/m3 of anatase TiO2 NPs (~20nm) during 6h.
      Rats were sacrificed at different time points over 14days following the onset of
      inhalation. Ti levels were quantified by ICP-MS in blood, tissues, and excreta.
      Oxidative damages were also monitored (MDA). Highest tissue levels of Ti were
      found in lungs; peak values were reached only at 48h followed by a progressive
      decrease over 14days, suggesting a persistence of NPs at the site-of-entry.
      Levels reached in blood, lymph nodes and other internal organs (including liver,
      kidney, spleen) were circa one order of magnitude lower than in lungs, but the
      profiles were indicative of a certain translocation to the systemic circulation.
      Large amounts were recovered in feces compared to urine, suggesting that inhaled
      NPs were eliminated mainly by mucociliary clearance and ingested. TiO2 NPs also
      appeared to be partly transferred to olfactory bulbs and brain. MDA levels
      indicative of oxidative damage were significantly increased in lungs and blood at
      24h but this was not clearly reflected at later times. Translocation and
      clearance rates of inhaled NPs under different realistic exposure conditions
      should be further documented.

PMID- 27884616
TI  - Mechanical properties of contact lenses: The contribution of measurement
      techniques and clinical feedback to 50 years of materials development.
AB  - PURPOSE: This review summarises the way in which mechanical property measurements
      combined with clinical perception have influenced the last half century of
      materials evolution in contact lens development. METHODS: Literature concerning
      the use of in-vitro testing in assessment of the mechanical behaviour of contact
      lenses, and the mutual deformation of the lens material and ocular tissue was
      examined. Tensile measurements of historic and available hydrogel lenses have
      been collected, in addition to manufacturer-generated figures for the moduli of
      commercial silicone hydrogel lenses. RESULTS: The three conventional modes of
      mechanical property testing; compression, tension and shear each represent
      different perspective in understanding the mutual interaction of the cornea and
      the contact lens. Tensile testing provides a measure of modulus, together with
      tensile strength and elongation to break, which all relate to handling and
      durability. Studies under compression also measure modulus and in particular
      indicate elastic response to eyelid load. Studies under shear conditions enable
      dynamic mechanical behaviour of the material to be assessed and the elastic and
      viscous components of modulus to be determined. These different methods of
      measurement have contributed to the interpretation of lens behaviour in the
      ocular environment. An amalgamated frequency distribution of tensile moduli for
      historic and currently available contact lens materials reveals the modal range
      to be 0.3-0.6MPa. CONCLUSION: Mechanical property measurements of lens materials
      have enabled calibration of an important aspect of their ocular interaction. This
      together with clinical feedback has influenced development of new lens materials
      and assisted clinical rationalisation of in-eye behaviour of different lenses.

PMID- 27884617
TI  - Trans advanced surface laser ablation (TransPRK) outcomes using
      SmartPulseTechnology.
AB  - PURPOSE: To evaluate early visual rehabilitation, post-operative pain, epithelial
      healing and haze after transepithelial photorefractive keratectomy (TransPRK)
      using the SmartPulseTechnology (SPT) of Schwind Amaris (Schwind eye-tech
      solutions GmbH, Kleinostheim, Germany). METHODS: This was a retrospective
      comparative evaluation of a cohort of myopic patients undergoing TransPRK with
      SPT (group 1), with one matched control group that underwent conventional
      TransPRK (group 2). All cases had a 6-month post-operative follow-up including
      visual acuity and slit-lamp examination. Subjective evaluation of pain was
      recorded post-operatively. RESULTS: 49 eyes of 25 patients in group 1 and 40 eyes
      of 20 patients in group 2 were enrolled. The patients' visual rehabilitation was
      significantly faster in group 1, one day and one week post-operatively (P<0.05).
      From one month onward there was no significant difference between the groups. The
      epithelial defect size was significantly smaller on post-operative days 1 and 2
      for group 1 (P<0.05 in both cases). The pain score was also significantly less in
      group 1 (P<0.05). The haze level had no significant difference between the groups
      at any post-operative point (P>0.05). DISCUSSION: TransPRK using SPT provides
      promising results in the early post-operative period. Visual rehabilitation, re
      epithelialization and pain were faster in the early post-operative period in
      group 1 in comparison with group 2. Haze formation was not significantly
      different between the two groups; however, it was consistently less in group 1.

PMID- 27884618
TI  - Effect of materials mixture on the higher heating value: Case of biomass, biochar
      and municipal solid waste.
AB  - The heating value describes the energy content of any fuel. In this study, this
      parameter was evaluated for different abundant materials in Morocco (two types of
      biochar, plastic, synthetic rubber, and cardboard as municipal solid waste (MSW),
      and various types of biomass). Before the evaluation of their higher heating
      value (HHV) by a calorimeter device, the thermal behavior of these materials was
      investigated using thermogravimetric (TGA) and Differential scanning calorimetry
      (DSC) analyses. The focus of this work is to evaluate the calorific value of each
      material alone in a first time, then to compare the experimental and theoretical
      HHV of their mixtures in a second time. The heating value of lignocellulosic
      materials was between 12.16 and 20.53MJ/kg, 27.39 for biochar 1, 32.60MJ/kg for
      biochar 2, 37.81 and 38.00MJ/kg for plastic and synthetic rubber respectively and
      13.81MJ/kg for cardboard. A significant difference was observed between the
      measured and estimated HHVs of mixtures. Experimentally, results for a large
      variety of mixture between biomass/biochar and biomass/MSW have shown that the
      interaction between biomass and other compounds expressed a synergy of 2.37% for
      biochar 1 and 6.11% for biochar 2, 1.09% for cardboard, 5.09% for plastic and
      5.01% for synthetic rubber.

PMID- 27884619
TI  - Inhibition on anammox bacteria upon exposure to digestates from biogas plants
      treating the organic fraction of municipal solid waste and the role of
      conductivity.
AB  - The aim of this research was to evaluate the applicability of the anammox process
      for removing nitrogen from the supernatant originating from the anaerobic
      digestion of the organic fraction of municipal solid waste (OFMSW). The short
      term inhibitory potential of this concentrated wastewater was evaluated by means
      of batch tests in terms of maximum specific anammox activity reduction. A total
      of 20 real wastewater samples were tested originating from 4 different full scale
      anaerobic digestion plants treating OFMSW. Activity reduction between 73% and 89%
      was observed in the presence of undiluted real wastewaters. The specific activity
      remained stable for 6-7days after the initial reduction, thus suggesting its
      treatability even without dilution. The inhibitory effect of both the real and
      synthetic saline media tested could be modelled as a function of conductivity.
      IC50 of 6.1mS/cm was obtained for exposure to the tested liquid fraction of
      biowaste digestate.

PMID- 27884620
TI  - Effect of dispersal in two-patch prey-predator system with positive density
      dependence growth of preys.
AB  - Prey-predator systems in patchy environment, connected through dispersal between
      patches is a very common phenomenon observed in nature, which have a significant
      impact in ecology, species persistence and extinction, etc. In the present paper,
      we consider a two patch prey-predator system where the patches are connected
      through dispersal between preys populations only. We consider positive density
      dependence growth for preys population. In addition, we consider the time scale
      difference (different life span) between preys and predator populations. From our
      study, we can conclude that dispersal can save both the populations from
      extinction, when in a single patch initial preys density is lower the Allee
      threshold. Also, time difference can increase the basin of attraction of the
      coexistence equilibrium of our two-patch model. Time scale difference also can
      help to reach the steady state faster than the without time scale difference, and
      it also causes the amplitude death when populations are in limit cycle
      oscillation. We also analyze our model by considering the time delay in dispersal
      dynamics, and we show that delay induced dispersal can stabilize the system and
      cause the amplitude death when individual populations are in the limit cycle,
      without dispersal. In addition, dispersal in non-identical patches can stabilize
      at its interior equilibrium even if the environment is harsh for both the
      populations in both the individual patches.

PMID- 27884622
TI  - Exercise modulates the aortic renin-angiotensin system independently of estrogen
      therapy in ovariectomized hypertensive rats.
AB  - The renin-angiotensin-system is an important component of cardiovascular control
      and is up-regulated under various conditions, including hypertension and
      menopause. The aim of this study was to evaluate the effects of swimming training
      and estrogen therapy (ET) on angiotensin-II (ANG II)-induced vasoconstriction and
      angiotensin-(1-7) [ANG-(1-7)]-induced vasorelaxation in aortic rings from
      ovariectomized spontaneously hypertensive rats. Animals were divided into Sham
      (SH), Ovariectomized (OVX), Ovariectomized treated with E2 (OE2), Ovariectomized
      plus swimming (OSW) and Ovariectomized treated with E2 plus swimming (OE2+SW)
      groups. ET entailed the administration of 5MUg of 17beta-Estradiol three times
      per week. Swimming was undertaken for sixty minutes each day, five times per
      week. Both, training and ET were initiated seven days following ovariectomy.
      Forty-eight hours after the last treatment or training session, the animals'
      systolic blood pressures were measured, and blood samples were collected to
      measure plasma ANG II and ANG-(1-7) levels via radioimmunoassay. In aortic rings,
      the vascular reactivity to ANG II and ANG-(1-7) was assessed. Expression of ANG
      (1-7) in aortic wall was analyzed by immunohistochemistry. The results showed
      that both exercise and ET increased plasma ANG II levels despite attenuating
      systolic blood pressure. Ovariectomy increased constrictor responses to ANG II
      and decreased dilatory responses to ANG-(1-7), which were reversed by swimming
      independently of ET. Moreover, it was observed an apparent increase in ANG-(1-7)
      content in the aorta of the groups subjected to training and ET. Exercise
      training may play a cardioprotective role independently of ET and may be an
      alternative to ET in hypertensive postmenopausal women.

PMID- 27884621
TI  - Photoantimicrobials-are we afraid of the light?
AB  - Although conventional antimicrobial drugs have been viewed as miraculous cure
      alls for the past 80 years, increasing antimicrobial drug resistance requires a
      major and rapid intervention. However, the development of novel but still
      conventional systemic antimicrobial agents, having only a single mode or site of
      action, will not alleviate the situation because it is probably only a matter of
      time until any such agents will also become ineffective. To continue to produce
      new agents based on this notion is unacceptable, and there is an increasing need
      for alternative approaches to the problem. By contrast, light-activated molecules
      called photoantimicrobials act locally via the in-situ production of highly
      reactive oxygen species, which simultaneously attack various biomolecular sites
      in the pathogenic target and therefore offer both multiple and variable sites of
      action. This non-specificity at the target circumvents conventional mechanisms of
      resistance and inhibits the development of resistance to the agents themselves.
      Photoantimicrobial therapy is safe and easy to implement and, unlike conventional
      agents, the activity spectrum of photoantimicrobials covers bacteria, fungi,
      viruses, and protozoa. However, clinical trials of these new, truly broad
      spectrum, and minimally toxic agents have been few, and the funding for research
      and development is almost non-existent. Photoantimicrobials constitute one of the
      few ways forward through the morass of drug-resistant infectious disease and
      should be fully explored. In this Personal View, we raise awareness of the novel
      photoantimicrobial technologies that offer a viable alternative to conventional
      drugs in many relevant application fields, and could thus slow the pace of
      resistance development.

PMID- 27884624
TI  - Serum IL-21 levels are elevated in atopic dermatitis patients with acute skin
      lesions.
AB  - BACKGROUND: Interleukin (IL)-21 is a member of the type I cytokine family and
      plays a role in the pathogenesis of T helper type 2 allergic diseases. It has
      been reported that IL-21 expression is upregulated in acute skin lesions in
      atopic dermatitis (AD) patients; however, little is known about the serum IL-21
      levels of AD patients. The aim of this study was to quantify the serum IL-21
      levels of AD patients and to evaluate the relationships between the serum IL-21
      level and disease severity, laboratory markers, and eruption type in AD patients.
      METHODS: We measured the serum IL-21 levels of adult AD patients and healthy
      control subjects using an enzyme-linked immunosorbent assay. RESULTS: The adult
      AD patients exhibited significantly higher serum IL-21 levels than the healthy
      control subjects. A comparison of the patients' serum IL-21 levels based on the
      clinical severity of their AD revealed that the patients with severe AD
      demonstrated significantly higher serum IL-21 levels than those with mild AD and
      the healthy control subjects. The serum IL-21 levels were significantly
      correlated with the skin severity score, and especially with the degree of acute
      lesions such as erythema and edema/papules. The serum IL-21 level was not
      associated with laboratory markers, such as the serum IgE level, the serum thymus
      and activation-related chemokine level, blood eosinophilia, and the serum lactate
      dehydrogenase level. CONCLUSIONS: These results suggest that IL-21 might be
      involved in the pathogenesis of AD, especially the development of acute skin
      lesions.

PMID- 27884623
TI  - Relationship between Toxoplasma gondii seropositivity and acoustic startle
      response in an inner-city population.
AB  - Toxoplasma gondii (TOXO) is a neuroinvasive protozoan parasite that induces the
      formation of persistent cysts in mammalian brains. It infects approximately
      1.1million people in the United States annually. Latent TOXO infection is
      implicated in the etiology of psychiatric disorders, especially schizophrenia
      (SCZ), and has been correlated with modestly impaired cognition. The acoustic
      startle response (ASR) is a reflex seen in all mammals. It is mediated by a
      simple subcortical circuit, and provides an indicator of neural function. We
      previously reported the association of TOXO with slowed acoustic startle latency,
      an index of neural processing speed, in a sample of schizophrenia and healthy
      control subjects. The alterations in neurobiology with TOXO latent infection may
      not be specific to schizophrenia. Therefore we examined TOXO in relation to
      acoustic startle in an urban, predominately African American, population with
      mixed psychiatric diagnoses, and healthy controls. Physiological and diagnostic
      data along with blood samples were collected from 364 outpatients treated at an
      inner-city hospital. TOXO status was determined with an ELISA assay for TOXO
      specific IgG. A discrete titer was calculated based on standard cut-points as an
      indicator of seropositivity, and the TOXO-specific IgG concentration served as
      serointensity. A series of linear regression models were used to assess the
      association of TOXO seropositivity and serointensity with ASR magnitude and
      latency in models adjusting for demographics and psychiatric diagnoses (PTSD,
      major depression, schizophrenia, psychosis, substance abuse). ASR magnitude was
      11.5% higher in TOXO seropositive subjects compared to seronegative individuals
      (p=0.01). This effect was more pronounced in models with TOXO serointensity that
      adjusted for sociodemographic covariates (F=7.41, p=0.0068; F=10.05, p=0.0017),
      and remained significant when psychiatric diagnoses were stepped into the models.
      TOXO showed no association with startle latency (t=0.49, p=0.63) in an unadjusted
      model, nor was TOXO associated with latency in models that included demographic
      factors. After stepping in individual psychiatric disorders, we found a
      significant association of latency with a diagnosis of PTSD (F=5.15, p=0.024),
      but no other psychiatric diagnoses, such that subjects with PTSD had longer
      startle latency. The mechanism by which TOXO infection is associated with high
      startle magnitude is not known, but possible mechanisms include TOXO cyst burden
      in the brain, parasite recrudescence, or molecular mimicry of a host epitope by
      TOXO. Future studies will focus on the neurobiology underlying the effects of
      latent TOXO infection as a potential inroad to the development of novel treatment
      targets for psychiatric disease.

PMID- 27884626
TI  - Update on some novel developments in transfusion science and medicine with global
      health implications.

PMID- 27884625
TI  - Complementary and alternative medicine for allergic rhinitis in Japan.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is extensively used in
      patients with allergic diseases worldwide. The purpose of this study was to
      investigate the actual situation of CAM practice in the treatment of allergic
      rhinitis. METHODS: We distributed questionnaires to otolaryngologists at 114
      facilities in Japan. The subjects who participated in this study included
      children <16 years of age and adults >=16 years of age diagnosed with allergic
      rhinitis by otolaryngologists. The survey was performed in the period from
      September 2007 to August 2009. Furthermore, we performed the same investigation
      out of the hospital setting, such as during general health examinations. All
      questionnaires were returned to Chiba University and analyzed. RESULTS: The
      proportions of patients who had ever experimented with CAM in the hospital survey
      were 7.1% (225/3170) and 19.2% (1416/7363) of children and adults, respectively.
      Approximately 36.2% of the adult patients thought that the treatments were
      effective. The main reasons for CAM use were safety, convenience and low price.
      However, the group who spent more than $1000 on CAM felt more dissatisfaction and
      anxiety related to treatment at the hospital. The situation of CAM practice was
      not consistent and was instead influenced by the backgrounds of the subjects.
      CONCLUSIONS: Many patients who receive CAM report feeling that the effects of
      treatment provided by hospitals are insufficient and have concerns about the side
      effects of such treatments. Information regarding standard treatments, as
      described in the guidelines, should become widely known and diffused, and strong
      communication with patients should be considered.

PMID- 27884628
TI  - Skirt followed by trouser stenting technique: True anatomical preservation of
      coronary Y-shaped bifurcation lesions while using "vanishing" bioresorbable
      scaffolds: A report of two cases.
AB  - We report on two cases in which Y-shaped coronary bifurcations were treated with
      the use of Bioresorbable scaffolds. The first case was of a 50-year-old man with
      NSTEMI. Coronary angiography showed stenosis involving a Y-shaped bifurcation of
      proximal to mid LAD and diagonal. The lesion was wired using two 0.14 BMW guide
      wires, followed by serial pre-dilatation of LAD and Diagonal branch. The stent
      into proximal LAD was deployed first as a skirt (3.5 * 12 BVS). Stent was post
      dilated. A second 2.5 * 28 BVS was deployed into diagonal branch, protruding
      backwards; along with a 2.0 * 15 SC balloon continuing into the mid LAD. Both
      balloons where pulled back proximally and re-inflated. The technique was repeated
      in reversed order for stenting the mid LAD using the third BVS (3.0 * 18 BVS).
      Finally two NC balloons where used to post-dilate both legs of the newly-formed
      trouser. The result was checked by OCT. The second case was that of a 62-year-old
      man with chest pain and NSTEMI. He had a history of previous PCI to LCx using
      bare metal stent. Coronary angiogram showed severe in-stent restenosis in mid
      LCX, extending into two large obtuse marginal branches. After wiring both OMs,
      serial pre-dilatation was done with two NC 2.5 * 20 balloons, followed by initial
      stenting of mid LCx inside old stent, as the proximal segment of bifurcation,
      using a 3.5 * 12 BVS, followed by implanting a 2.5 * 28 BVS into OM2 and 2.5 * 18
      into OM1. At 6 months a clinical follow up via telephone contact revealed no
      recurrence of chest pain in both cases and no further intervention required.

PMID- 27884627
TI  - Characterization of avian paramyxovirus serotype 14, a novel serotype, isolated
      from a duck fecal sample in Japan.
AB  - A hemagglutinating virus isolate designated 11OG0352, was obtained from a duck
      fecal sample. Genetic and virological analyses indicated that it might represent
      a novel serotype of avian paramyxovirus (APMV). Electron micrographs showed that
      the morphology of the virus particle was similar to that of APMV. The complete
      genome of this virus comprised 15,444 nucleotides complying with the
      paramyxovirus "rule of six" and contains six open reading frames (3'-N-P-M-F-HN-L
      5'). The phylogenetic analysis of the whole genome revealed that the virus was a
      member of the genus Avulavirus, but that it was distinct from APMV-1 to APMV-13.
      Although the F-protein cleavage site was TREGK?L, which resembles a lentogenic
      strain of APMV-1, the K residue at position -1 of the cleavage site was first
      discovered in APMV members. The phosphoprotein gene of isolate 11OG0352 contains
      a putative RNA editing site, 3'-AUUUUCCC-5' (negative sense) which sequence
      differs from that of other APMVs. The intracerebral pathogenicity index test did
      not detect virulence in infected chicks. In hemagglutination inhibition (HI)
      tests, an antiserum against this virus did not detectably react with other APMVs
      (serotypes 1-4, 6-9) except for low reciprocal cross-reactivity with APMV-6. We
      designated this isolate, as APMV-14/duck/Japan/11OG0352/2011 and propose that it
      is a novel APMV serotype. The HI test may not be widely applicable for the
      classification of a new serotype because of the limited availability of reference
      antisera against all serotypes and cross-reactivity data. The nucleotide sequence
      identities of the whole genome of 11OG0352 and other APMVs ranged from 46.3% to
      56.1%. Such comparison may provide a useful tool for classifying new APMV
      isolates. However, the nucleotide sequence identity between APMV-12 and APMV-13
      was higher (64%), which was nearly identical to the lowest nucleotide identity
      (67%) reported in subgroups within the serotype. Therefore, consensus criteria
      for using whole genome analysis should be established.

PMID- 27884629
TI  - Urgent listing exceptions and outcomes in pediatric heart transplantation:
      Comparison to standard criteria patients.
AB  - BACKGROUND: United Network for Organ Sharing (UNOS) policy enables listing
      exceptions to avoid penalizing patients with waitlist mortality not captured by
      standard criteria. Outcomes among patients listed by exception have not been
      analyzed. METHODS: We performed a retrospective analysis of pediatric (<=17 years
      of age, n = 4,706) listings (2006 to 2015) for primary, isolated heart
      transplantation within the UNOS data set, assessing Status 1A exception (n = 211,
      4.5%) use across regions and patient characteristics and evaluating waitlist
      outcomes compared with candidates listed using standard criteria. RESULTS: Death
      or removal for reason other than transplant did not differ between exception and
      standard criteria patients at 1 month (11.7% vs 16.2%, p = not statistically
      significant [NS]), 2 months (18.2% vs 29.0%, p = 0.11) or overall (16.1% vs
      22.0%, p = NS) on the waitlist. Rates were higher than among Status 1B patients
      (1 month: 2.8%; 2 months: 5.6%; overall: 14.9%; p < 0.0001). The cumulative
      incidence of competing risks (transplantation, death/removal for reasons other
      than transplant and removal) did not differ when comparing Status 1A exception
      patients with Status 1A standard criteria patients. Use of 1A exceptions varied
      across UNOS regions (1.9% to 22.3%, p < 0.0001). Risk-adjusted modeling
      identified patients more (hypertrophic cardiomyopathy: odds ratio [OR] = 2.8, 95%
      confidence interval [CI] 1.5 to 5.0; restrictive cardiomyopathy: OR = 2.7, 95% CI
      1.7 to 4.3) and less (low socioeconomic status: OR = 0.7, 95% CI 0.5 to 1.0)
      likely to use an exception. Use of exceptions was uncorrelated with regional
      outcomes. CONCLUSIONS: Waitlist mortality among Status 1A exception patients is
      similar to that among those listed by standard criteria. However, variation in
      exception use across geography and demography may contribute to inequities in
      access to transplantation, particularly for those with low socioeconomic status.
      Standardization of practices may decrease regional variation and minimize
      inequities.

PMID- 27884630
TI  - Psychometric testing of Korean versions of self-efficacy and outcome expectations
      for restorative care activities scales.
AB  - This study aimed to examine the validity and reliability of Korean versions of
      the Nursing Assistant Self-Efficacy for Restorative Care Scale, and the Nursing
      Assistant Outcome Expectations for Restorative Care Scale. Psychometric testing
      was performed with 697 direct care workers in long-term care facilities in South
      Korea. Data were analyzed using SPSS/WIN 21.0, AMOS 22.0, and WINSTEPS 3.68.2.
      There was evidence for content validity. Factor loading in the Korean versions of
      the Nursing Assistant Self-Efficacy for Restorative Care Scale was 0.66-0.94, and
      Nursing Assistant Outcome Expectations for Restorative Care Scale was 0.43-0.77.
      Scores on the Korean versions of the Nursing Assistant Outcome Expectations for
      Restorative Care Scale correlated positively with scores on a scale of knowledge
      of restorative care. Additionally, Rasch model analysis of the K-NASERC and K
      NAOERC indicates acceptable item data fit. These results indicated that the
      Korean versions of the Nursing Assistant Self-Efficacy, and Outcome Expectations
      for Restorative Care Scale are satisfactorily valid and reliable for the
      measurement.

PMID- 27884631
TI  - Out of the Darkness and Into the Light: Patients, Referring Physicians, and
      Radiologists Working Toward Patient- and Family-Centered Care in Radiology.

PMID- 27884633
TI  - Recent Trends in Imaging Use in Hospital Settings: Implications for Future
      Planning.
AB  - PURPOSE: To compare trends in utilization rates of imaging in the three hospital
      based settings where imaging is conducted. METHODS: The nationwide Medicare Part
      B databases for 2004-2014 were used. All discretionary noninvasive diagnostic
      imaging (NDI) CPT codes were selected and grouped by modality. Procedure volumes
      of each code were available from the databases and converted to utilization rates
      per 1,000 Medicare enrollees. Medicare's place-of-service codes were used to
      identify imaging examinations done in hospital inpatients, hospital outpatient
      departments (HOPDs), and emergency departments (EDs). Trends were observed over
      the life of the study. RESULTS: Trendlines were strongly affected by code
      bundling in echocardiography in 2009, nuclear imaging in 2010, and CT in 2011.
      However, even aside from these artifactual effects, important trends could be
      discerned. Inpatient imaging utilization rates of all modalities are trending
      downward. In HOPDs, the utilization rate of conventional radiographic
      examinations (CREs) is declining but rates of CT, MRI, echocardiography, and
      noncardiac ultrasound (US) are increasing. In EDs, utilization rates of CREs, CT,
      and US are increasing. In the 3 years after 2011, when no further code bundling
      occurred, the total inpatient NDI utilization rate dropped 15%, whereas the rate
      in EDs increased 12% and that in HOPDs increased 1%. CONCLUSIONS: The trends in
      utilization of NDI in the three hospital-based settings where imaging occurs are
      distinctly different. Radiologists and others who are involved in deciding what
      kinds of equipment to purchase and where to locate it should be cognizant of
      these trends in making their decisions.

PMID- 27884632
TI  - Strategies for Improving the Value of the Radiology Report: A Retrospective
      Analysis of Errors in Formally Over-read Studies.
AB  - PURPOSE: The radiology report is a critical component of the Imaging Value Chain.
      Unfortunately, the quality of this aspect of a radiologist's work is often
      heterogeneous and fails to add significant value to the referring provider and,
      ultimately, the patient. Gauging what defines quality can be elusive; however, we
      elucidate techniques that can be employed to ensure that reports are more
      comprehensible, actionable, and useful to our customers. METHODS: Four hundred
      consecutive studies (July-August 2015) submitted to our institution with request
      for a formal over-read were reviewed retrospectively, specifically focused on
      analyzing differences in language, organization, and impression between the
      outside reports and the formal over-reads performed at our institution. The
      formal over-reads were classified into one of the following categories: (1) no
      clinically significant change; (2) emergent clinically significant change; (3)
      nonemergent clinically significant change. Clinically significant changes were
      further classified as either perceptual or cognitive errors. RESULTS: A total of
      12.4% of formally over-read reports had clinically significant changes. Of these,
      22.2% were emergent changes. Clinically significant changes were composed of
      64.4% perceptual error and 35.6% cognitive error. Four strategies were discovered
      specifically related to reporting techniques that helped mitigate these errors on
      formal over-reads: (1) synthesizing varied anatomic findings into a cohesive
      disease process; (2) integration of relevant electronic health record data; (3)
      use of structured reporting; and (4) forming actionable impressions. CONCLUSIONS:
      We identify, through examples, four strategies for reporting that add value
      through reduction of radiologic error, helping to mitigate the 12.4% clinically
      significant error rate found in reinterpretation of outside studies.

PMID- 27884634
TI  - Late Strut Fracture Within a Partially Resorbed Bioresorbable Vascular Scaffold:
      A Possible Cause of Late Scaffold Thrombosis and Acute Coronary Syndrome.
AB  - The Bioresorbable Vascular Scaffold (BVS, Abbott Vascular, Santa Clara, Cal, USA)
      is an exciting advance in percutaneous coronary intervention providing a
      temporary drug eluting scaffold resorbed in two to five years. We present two
      cases of late scaffold thrombosis associated with strut fracture during the
      period of resorption, at 20 and 24 months following BVS implantation. We propose
      luminal migration of malapposed struts following strut fracture during resorption
      as a potential mechanism for late scaffold thrombosis and acute coronary
      syndrome.

PMID- 27884635
TI  - Understand protein functions by comparing the similarity of local structural
      environments.
AB  - The three-dimensional structures of proteins play an essential role in regulating
      binding between proteins and their partners, offering a direct relationship
      between structures and functions of proteins. It is widely accepted that the
      function of a protein can be determined if its structure is similar to other
      proteins whose functions are known. However, it is also observed that proteins
      with similar global structures do not necessarily correspond to the same
      function, while proteins with very different folds can share similar functions.
      This indicates that function similarity is originated from the local structural
      information of proteins instead of their global shapes. We assume that proteins
      with similar local environments prefer binding to similar types of molecular
      targets. In order to testify this assumption, we designed a new structural
      indicator to define the similarity of local environment between residues in
      different proteins. This indicator was further used to calculate the probability
      that a given residue binds to a specific type of structural neighbors, including
      DNA, RNA, small molecules and proteins. After applying the method to a large
      scale non-redundant database of proteins, we show that the positive signal of
      binding probability calculated from the local structural indicator is
      statistically meaningful. In summary, our studies suggested that the local
      environment of residues in a protein is a good indicator to recognize specific
      binding partners of the protein. The new method could be a potential addition to
      a suite of existing template-based approaches for protein function prediction.

PMID- 27884636
TI  - An in vitro and in vivo study of peptide-functionalized nanoparticles for brain
      targeting: The importance of selective blood-brain barrier uptake.
AB  - Targeted delivery of drugs across endothelial barriers remains a formidable
      challenge, especially in the case of the brain, where the blood-brain barrier
      severely limits entry of drugs into the central nervous system. Nanoparticle
      mediated transport of peptide/protein-based drugs across endothelial barriers
      shows great potential as a therapeutic strategy in a wide variety of diseases.
      Functionalizing nanoparticles with peptides allows for more efficient targeting
      to specific organs. We have evaluated the hemocompatibilty, cytotoxicity,
      endothelial uptake, efficacy of delivery and safety of liposome, hyperbranched
      polyester, poly(glycidol) and acrylamide-based nanoparticles functionalized with
      peptides targeting brain endothelial receptors, in vitro and in vivo. We used an
      ELISA-based method for the detection of nanoparticles in biological fluids,
      investigating the blood clearance rate and in vivo biodistribution of labeled
      nanoparticles in the brain after intravenous injection in Wistar rats. Herein, we
      provide a detailed report of in vitro and in vivo observations.

PMID- 27884637
TI  - Phototheranostic nanoplatform based on a single cyanine dye for image-guided
      combinatorial phototherapy.
AB  - This study represents a novel phototheranostic nanoplatform based on the near
      infrared (NIR) heptamethine cyanine dye, IR775, which is capable of concurrent
      real-time fluorescence imaging and cancer eradication with combinatorial
      phototherapy. To achieve water solubility and enhance tumor delivery, the
      hydrophobic IR775 dye was loaded into a biocompatible polymeric nanoparticle with
      a diameter of ~40nm and slightly negative surface charge (-2.34mV). The
      nanoparticle-encapsulated hydrophobic IR775 dye (IR775-NP) is characterized by an
      enhanced fluorescence quantum yield (16%) when compared to the water soluble
      analogs such as ICG (2.7%) and IR783 (8%). Furthermore, the developed IR-775-NP
      efficiently generates both heat and reactive oxygen species under NIR light
      irradiation, eradicating cancer cells in vitro. Finally, animal studies revealed
      that the IR775-NP accumulates in cancer tumors after systemic administration,
      efficiently delineates them with NIR fluorescence signal and completely
      eradicates chemo resistant cancer tissue after a single dose of combinatorial
      phototherapy.

PMID- 27884638
TI  - Particle size effect of curcumin nanosuspensions on cytotoxicity, cellular
      internalization, in vivo pharmacokinetics and biodistribution.
AB  - This study aimed to investigate the particle size effect on bioactivity, cellular
      internalization and bioavailability of curcumin (CUR) nanosuspension (CUR-NS).
      CUR-NSs of different particle sizes were prepared by two different anti-solvent
      precipitation methods. CUR-NS with the smallest size showed similar in vitro
      anticancer activity and bioavailability to the CUR solution, whereas
      nanosuspensions of larger particle sizes displayed higher in vitro cellular
      internalization and cytotoxicity, as well as higher in vivo AUC and slower
      clearance rate after i.v. administration in rats. CUR solution and different
      sized CUR-NSs reached the highest concentrations in the lung, followed by liver
      and spleen while the lowest concentration was observed in the brain after i.v.
      administration in mice. Specifically, CUR-NS of 70nm accumulated more in the
      brain, whereas CUR-NS of 200nm accrued more in liver and spleen. CUR-NS of 20nm
      displayed no significant biodistribution difference compared with CUR solution in
      all tissues.

PMID- 27884639
TI  - Amphiphilic poly-N-vinylpyrrolidone nanoparticles as carriers for non-steroidal,
      anti-inflammatory drugs: In vitro cytotoxicity and in vivo acute toxicity study.
AB  - Polymeric nanoparticles were prepared from self-assembled amphiphilic N
      vinylpyrrolidone polymers in aqueous media and evaluated as novel carriers of
      indomethacin, a non-steroidal, anti-inflammatory drug. It was determined that
      these nanoparticles could be created in spherical morphologies with sizes less
      than 100nm, narrow size distributions and high indomethacin contents(up to 35%)
      combined with high drug loading efficiencies(up to 95%). In cytotoxicity tests
      using the human embryonic stem cell derived fibroblasts (EBF-H9) and
      hepatocellular carcinoma cells (HepG2), the indomethacin-loaded polymeric
      nanoparticles showed higher cell viability compared to that of free indomethacin
      at the same concentration. The median LD50 values, determined by the Litchfield
      Wilcoxon method, were 55-70mg/kg body weight depending on the polymer molecular
      design in both mice and rats. Based on the acquired results, these novel
      amphiphilic poly-N-vinylpyrrolidone nanoparticles can be considered as potential
      carriers for new, highly efficient, injectable drug delivery systems for
      hydrophobic drugs such as indomethacin.

PMID- 27884640
TI  - Biodegradation of the ZnO:Eu nanoparticles in the tissues of adult mouse after
      alimentary application.
AB  - Biodegradable zinc oxide nanoparticles (ZnO NPs) are considered promising
      materials for future biomedical applications. To fulfil this potential,
      biodistribution and elimination patterns of ZnO NPs in the living organism need
      to be resolved. In order to investigate gastrointestinal absorption of ZnO NPs
      and their intra-organism distribution, water suspension of ZnO or fluorescent
      ZnO:Eu (Europium-doped zinc oxide) NPs (10mg/ml; 0.3ml/mouse) was alimentary
      administered (IG: intra-gastric) to adult mice. Internal organs collected at key
      time-points after IG were evaluated by AAS for Zn concentration and analysed by
      cytometric techniques. We found that Zn-based NPs were readily absorbed and
      distributed (3 h post IG) in the nanoparticle form throughout the organism.
      Results suggest, that liver and kidneys were key organs responsible for NPs
      elimination, while accumulation was observed in the spleen and adipose tissues.
      We also showed that ZnO/ZnO:Eu NPs were able to cross majority of biological
      barriers in the organism (including blood-brain-barrier).

PMID- 27884642
TI  - Psychiatric comorbidities in epilepsy: Should they be considered in the
      classification of epileptic disorders?
AB  - The prevalence of psychiatric comorbidities is relatively high in people with
      epilepsy (PWE), as one in three patients will have experienced a psychiatric
      disorder in the course of their life. The new definition of epilepsy recognizes
      these comorbidities as part of the seizure disorder, which need to be recognized
      and treated together with the actual epileptic seizures. Psychiatric
      comorbidities have a complex relation with epilepsy, being associated with a
      negative course of the seizure disorder, worse tolerance of pharmacotherapy with
      AEDs, development of iatrogenic psychiatric complications from pharmacologic and
      surgical treatments, and increased mortality risks. Given their negative impact
      at several levels of the lives of PWE, should psychiatric comorbidities be
      included in a classification of the epilepsies? This question is addressed in
      this article. This article is part of a Special Issue entitled "The new approach
      to classification: Rethinking cognition and behavior in epilepsy".

PMID- 27884643
TI  - Transcatheter Aortic Valve Implantation in Patients With Arterial Peripheral
      Vascular Disease.

PMID- 27884641
TI  - Nanoparticle delivery of chemotherapy combination regimen improves the
      therapeutic efficacy in mouse models of lung cancer.
AB  - The combination chemotherapy regimen of cisplatin (CP) and docetaxel (DTX) is
      effective against a variety of cancers. However, combination therapies present
      unique challenges that can complicate clinical application, such as increases in
      toxicity and imprecise exposure of tumors to specific drug ratios that can
      produce treatment resistance. Drug co-encapsulation within a single nanoparticle
      (NP) formulation can overcome these challenges and further improve combinations'
      therapeutic index. In this report, we employ a CP prodrug (CPP) strategy to
      formulate poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs
      carrying both CPP and DTX. The dually loaded NPs display differences in drug
      release kinetics and in vitro cytotoxicity based on the structure of the chosen
      CPP. Furthermore, NPs containing both drugs showed a significant improvement in
      treatment efficacy versus the free drug combination in vivo.

PMID- 27884644
TI  - Evaluating augmentation with calcium phosphate cement (chronOS Inject) for bone
      defects after internal fixation of proximal tibial fractures: A prospective,
      multicenter, observational study.
AB  - INTRODUCTION: Managing subchondral bone defects in proximal tibia fractures after
      plateau reduction is an important consideration. ChronOS Inject is a recently
      developed calcium phosphate bone substitute that shows relatively fast
      osteointegration. HYPOTHESIS: Using chronOS Inject during internal fixation of
      proximal tibial fractures provides a satisfactory treatment option that is both
      clinically and radiologically safe. PATIENTS AND METHODS: Patients enrolled in
      this study were treated with chronOS Inject bone void filler, during internal
      fixation of proximal tibial fractures. Patients were evaluated preoperatively and
      at 6 weeks, 6 and 12 months postoperative. Radiographic union was assessed using
      plain films supplemented by CT scans. Pain, function and adverse events were
      collected at all visits. A total of 36 patients were enrolled in the study and
      treated according to a predetermined protocol. Seven of the 36 patients (19.4%)
      were lost to follow-up. RESULTS: Successful radiographic union was achieved in
      27/29 (93.1%) of patients at final follow-up. Articular subsidence of>2mm only
      occurred in one patient. Statistical analysis showed significant improvements
      both in leg pain and knee function. Progress in knee function was observed in
      93.1% (27/29) of patients from 6 weeks to 12 months. No product-related
      complications were reported. CONCLUSIONS: Successful union was achieved based on
      radiographic criteria as well as clinical outcomes. When managing bone defects
      after internal fixation of proximal tibial fractures, the use of chronOS Inject
      resulted in significant improvement of knee function and reduction of leg pain.
      LEVEL OF EVIDENCE: Level IV, prospective observational study.

PMID- 27884647
TI  - Salt, Tomato Soup, and the Hypocrisy of the American Heart Association.

PMID- 27884646
TI  - MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly
      targeting histone deacetylase 2 in chondrogenesis and degradation.
AB  - OBJECTIVE: Increased activity of histone deacetylase 2 (HDAC2) has been found in
      patients with osteoarthritis (OA) and cartilage matrix degradation and has been
      shown to mediate the repression of cartilage-specific gene expression in human
      chondrocytes. We aimed to determine whether microRNA-92a-3p (miR-92a-3p)
      regulates cartilage-specific gene expression via targeted HDAC2 in chondrogenesis
      and degradation. METHODS: miR-92a-3p expression was assessed in vitro in a human
      mesenchymal stem cells (hMSCs) model of chondrogenesis and in normal and OA
      primary human chondrocytes (PHCs), and in normal and OA human cartilage by in
      situ hybridization. hMSCs and PHCs were transfected with miR-92a-3p or its
      antisense inhibitor (anti-miR-92a-3p), respectively. PHCs were transfected with
      miR-92a-3p or anti-miR-92a-3p for 24 h before chromatin immunoprecipitation
      (ChIP) assay was performed with anti-ac-H3 antibody. Direct interaction between
      miR-92a-3p and its putative binding site in the 3'-untranslated region (3'-UTR)
      of HDAC2 mRNA was confirmed by luciferase reporter assay. RESULTS: miR-92a-3p
      expression was elevated in chondrogenic and hypertrophic hMSC, while reduced in
      OA cartilage compared with normal cartilage. The overexpression of miR-92a-3p
      suppressed the activity of a reporter construct containing the 3'-UTR and
      inhibited HDAC2 expression in both hMSCs and PHCs, while treatment with anti-miR
      92a-3p enhanced HDAC2 expression. ChIP assays showed that miR-92a-3p enhances H3
      acetylation on aggrecan (ACAN), cartilage oligomeric protein (COMP) and Col2a1
      promoter, and also promotes relative cartilage matrix expression. CONCLUSION: Our
      results suggest that miR-92a-3p regulates cartilage development and homeostasis,
      which directly targets HDAC2, indicating histone hyperacetylation plays an
      important role in increased expression of cartilage matrix.

PMID- 27884645
TI  - Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1
      suppression alters TGF-beta signaling in chondrocytes.
AB  - OBJECTIVES: Circadian rhythm (CR) was identified by RNA sequencing as the most
      dysregulated pathway in human osteoarthritis (OA) in articular cartilage. This
      study examined circadian rhythmicity in cultured chondrocytes and the role of the
      CR genes NR1D1 and BMAL1 in regulating chondrocyte functions. METHODS: RNA was
      extracted from normal and OA-affected human knee cartilage (n = 14 each).
      Expression levels of NR1D1 and BMAL1 mRNA and protein were assessed by
      quantitative PCR and immunohistochemistry. Human chondrocytes were synchronized
      and harvested at regular intervals to examine circadian rhythmicity in RNA and
      protein expression. Chondrocytes were treated with small interfering RNA (siRNA)
      for NR1D1 or BMAL1, followed by RNA sequencing and analysis of the effects on the
      transforming growth factor beta (TGF-beta) pathway. RESULTS: NR1D1 and BMAL1 mRNA
      and protein levels were significantly reduced in OA compared to normal cartilage.
      In cultured human chondrocytes, a clear circadian rhythmicity was observed for
      NR1D1 and BMAL1. Increased BMAL1 expression was observed after knocking down
      NR1D1, and decreased NR1D1 levels were observed after knocking down BMAL1.
      Sequencing of RNA from chondrocytes treated with NR1D1 or BMAL1 siRNA identified
      330 and 68 significantly different genes, respectively, and this predominantly
      affected the TGF-beta signaling pathway. CONCLUSIONS: The CR pathway is
      dysregulated in OA cartilage. Interference with circadian rhythmicity in cultured
      chondrocytes affects TGF-beta signaling, which is a central pathway in cartilage
      homeostasis.

PMID- 27884649
TI  - Trends and Disparities in Osteoporosis Screening Among Women in the United
      States, 2008-2014.
AB  - BACKGROUND: The United States Preventive Services Task Force recommends universal
      osteoporosis screening among women ages 65+ and targeted screening of younger
      women, but historically, adherence to these evidence-based recommendations has
      been suboptimal. METHODS: To describe contemporary patterns of osteoporosis
      screening, we conducted a retrospective analysis using the OptumLabsTM Data
      Warehouse, a database of de-identified administrative claims, which includes
      medical and eligibility information for over 100 million Medicare Advantage and
      commercial enrollees. Study participants included 1,638,454 women ages 50+ with
      no prior history of osteoporosis diagnosis, osteoporosis drug use, or hip
      fracture. Osteoporosis screening during the most recent 2-year period of
      continuous enrollment was assessed via medical claims. Patient sociodemographics,
      comorbidities, and utilization of other services were also determined using
      health insurance files. RESULTS: Overall screening rates were low: 21.1%, 26.5%,
      and 12.8% among women ages 50-64, 65-79, and 80+ years, respectively. Secular
      trends differed significantly by age (P <.001). Between 2008 and 2014,
      utilization among women ages 50-64 years declined 31.4%, changed little among
      women 65-79, and increased 37.7% among women 80+ years. Even after accounting for
      socioeconomic status, health status, and health care utilization patterns, non
      Hispanic black women were least likely to be screened, whereas non-Hispanic Asian
      and Hispanic women were most likely to undergo screening. Marked socioeconomic
      gradients in screening probabilities narrowed substantially over time, decreasing
      by 44.5%, 71.9%, and 59.7% among women ages 50-64, 65-79 and 80+ years,
      respectively. CONCLUSIONS: Despite significant changes in utilization of
      osteoporosis screening among women ages 50-64 and 80+, in line with national
      recommendations, tremendous deficiencies among women 65+ remain.

PMID- 27884648
TI  - Dipeptidyl Peptidase-4 Inhibitors, Peripheral Arterial Disease, and Lower
      Extremity Amputation Risk in Diabetic Patients.
AB  - BACKGROUND: Recent studies have elucidated the vascular protective effects of
      dipeptidyl peptidase-4 (DPP-4) inhibitors. However, to date, no large-scale
      studies have been carried out to determine the impact of DPP-4 inhibitors on the
      occurrence of peripheral arterial disease, and lower extremity amputation risk in
      patients with type 2 diabetes mellitus. METHODS: We conducted a retrospective
      registry analysis using Taiwan's National Health Insurance Research Database to
      investigate the correlation between the use of DPP-4 inhibitors and risk of
      peripheral arterial disease in patients with type 2 diabetes mellitus. A total of
      82,169 propensity score-matched pairs of DPP-4 inhibitor users and nonusers with
      type 2 diabetes mellitus were examined for the period 2009 to 2011. RESULTS: The
      mean age of the study subjects was 58.9 +/- 12.0 years, and 54% of subjects were
      male. During the mean follow-up of 3.0 years (maximum, 4.8 years), a total of
      3369 DPP-4 inhibitor users and 3880 DPP-4 inhibitor nonusers were diagnosed with
      peripheral arterial disease. Compared with nonusers, DPP-4 inhibitor users were
      associated with a lower risk of peripheral arterial disease (hazard ratio 0.84;
      95% confidence interval, 0.80-0.88). Additionally, DPP-4 inhibitor users had a
      decreased risk of lower-extremity amputation than nonusers (hazard ratio 0.65;
      95% confidence interval, 0.54-0.79). The association between use of DPP-4
      inhibitors and risk of peripheral arterial disease was also consistent in
      subgroup analysis. CONCLUSIONS: This large-scale nationwide population-based
      cohort study is the first to demonstrate that treatment with DPP-4 inhibitors is
      associated with lower risk of peripheral arterial disease occurrence and limb
      amputation in patients with type 2 diabetes mellitus.

PMID- 27884651
TI  - Analysis of mutations in DNA gyrase and topoisomerase IV of Ureaplasma
      urealyticum and Ureaplasma parvum serovars resistant to fluoroquinolones.
AB  - This study aims to determine the prevalence of fluoroquinolone resistance of
      Ureaplasma biovars and serovars isolated from urogenital clinical samples and
      determine the underlying molecular mechanism for quinolone resistance for all
      resistant isolates. Of 105 samples confirmed as positive for U. urealyticum/U.
      parvum, 85 were resistant to quinolones by the Mycoplasma-IST2 kit. However, only
      43 out of 85 quinolone resistant isolates had amino acid substitutions in GyrA,
      GyrB, ParC and ParE proteins underlining that this assay have mis-identified as
      fluoroquinolone resistant 42 isolates. The known ParC E87K and ParC S83L
      mutations were found in 1 and 10 isolates, respectively. An original mutation of
      ureaplasmal ParC (E87Q, 1 isolate) was found. Furthermore, we found a ParE R448K
      mutation in one isolate, already described. Among the additional alterations
      detected, the most prevalent mutation found was L176F in GyrA protein in 18
      isolates with single infection and in 3 isolates with mixed ureaplasma
      infections. Mutations in GyrB (E502Q, 4 isolates), ParE (Q412K, Q412P, Q412T, 3
      independent isolates), whose role is unknown, were also found. Other sporadic
      mutations in the four genes were identified. This investigation is the result of
      monitoring the data for molecular fluoroquinone resistance in Ureaplasma spp. in
      Italy. Resulting that this acquired resistance is high and that continued local
      epidemiological studies are essential to monitor and document their antimicrobial
      resistance trends.

PMID- 27884652
TI  - Clinical and molecular epidemiologic trends reveal the important role of
      rotavirus in adult infectious gastroenteritis, in Shanghai, China.
AB  - As a leading cause of severe diarrhea in children, the pathogenic role of
      rotavirus in adults has been underestimated for a long time. A hospital-based
      prospective clinical and molecular epidemiologic study of rotavirus infections in
      adults was performed between April 2014 and March 2015 in Shanghai, China.
      Overall, rotavirus was detected in 48 of 441 (10.9%) specimens with prevalence
      peaking in December (33.3%) and January (27.9%), whereas bacteria were identified
      in 45 of 846 (5.3%) samples (p<0.01). The rotavirus winter-spring seasonality
      (November - March) contrasts with the marked summer-fall seasonality (April -
      October) of bacterial pathogens (p<0.01). Compared with bacterial pathogens,
      rotavirus infection from child-to-adult transmission (29.8%, p<0.01) was the most
      important epidemiologic setting generating a major impact on public health, i.e.
      increased adult burden of infectious gastroenteritis and genetic diversity of
      circulating rotaviruses; adults infected with rotavirus developed more severe
      gastroenteritis symptoms (p<0.01) accompanied with mild intestinal and blood
      inflammations. Thirty-three G9 (lineages VIe and IIId), seven G2 (lineages IVa-1,
      IVa-3, and V) and two G1 (lineage Va) strains, together with thirty-eight P[8]
      III and eight P[4]-V strains, were identified in this study with multiple amino
      acid differences observed between sample strains and homotypic vaccines. G9P[8]
      was the predominant genotype (66.7%), followed by G2P[4] (14.6%) and G1P[8]
      (4.2%). Eight conserved amino acid substitutions in prototype strain K-1,
      especially A212T in antigenic region C, formed a novel G9-lineage VIe variant
      that has emerged worldwide since 2010. Our results indicated that emerging
      rotavirus G9-VIeP[8]-III predominated over all the genotypes with a short time
      window in adults in Shanghai, China, and caused a local epidemic during the 2014
      2015 rotavirus season. These findings reinforce the importance for inclusion of
      rotavirus in routine clinical diagnosis, and further surveillance of rotavirus
      variants is recommended to improve current vaccination program.

PMID- 27884653
TI  - Migration, recombination, and reassortment are involved in the evolution of
      severe fever with thrombocytopenia syndrome bunyavirus.
AB  - Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) has been
      identified as the etiological agent causing severe fever with thrombocytopenia
      syndrome (SFTS). SFTSV was reported in recent years as a newly emerging tick
      borne virus in China, Japan and South Korea and is a novel member of the genus
      Phlebovirus, family Bunyaviridae, which is suspected to be transmitted by the
      tick Haemaphysalis longicornis. The genetic diversity and evolutionary
      relationships between geographically distributed SFTSV strains are currently
      unclear. In this study we used extensive bioinformatics analyses to provide deep
      insight into the mechanisms of evolution and relationships among SFTSV strains.
      The genetic diversity of SFTSV was characterized and found to be generated
      through recombination and reassortment events. Further, potential correlations
      between the geographic distribution and migration pathways of SFTSV were subject
      to in-depth analysis. The potential of birds migration related to SFTSV migration
      were also discussed. The results of this study will facilitate better
      understanding of the mechanisms of evolution of SFTSV, which will be important in
      developing public-health interventions and strategies for SFTS disease control
      and prevention in endemic areas.

PMID- 27884650
TI  - The Clinical Course of Venous Thromboembolism May Differ According to Cancer
      Site.
AB  - BACKGROUND: We hypothesized that the clinical course of venous thromboembolism in
      patients with active cancer may differ according to the specificities of primary
      tumor site. AIM AND METHODS: We used data from RIETE (international registry of
      patients with venous thromboembolism) to compare the clinical venous
      thromboembolism-related outcomes during the course of anticoagulation in patients
      with one of the 4 more frequent cancers (breast, prostate, colorectal, or lung
      cancer). RESULTS: As of September 2014, 3947 cancer patients were recruited, of
      whom 938 had breast, 629 prostate, 1189 colorectal, and 1191 lung cancer.
      Overall, 55% had metastatic disease (42%, 36%, 53%, and 72%, respectively).
      During the course of anticoagulant therapy (mean duration, 139 days), the rate of
      thromboembolic recurrences was similar to the rate of major bleeding in patients
      with breast (5.6 [95% confidence interval (CI), 3.8-8.1] vs 4.1 [95% CI, 2.7-5.9]
      events per 100 patient-years) or colorectal cancer (10 [95% CI, 7.6-13] vs 12
      [95% CI, 9.4-15] per 100 patient-years). In contrast, in patients with prostate
      cancer, the rate of venous thromboembolic recurrences was half the rate of major
      bleeding (6.9 [95% CI, 4.4-10] vs 13 [95% CI, 9.2-17] events per 100 patient
      years), whereas in those with lung cancer, the rate of thromboembolic recurrences
      was twofold higher than the rate of major bleeding (27 [95% CI, 22-23] vs 11 [95%
      CI, 8.6-15] per 100 patient-years). CONCLUSIONS: Significant differences in the
      clinical profile of venous thromboembolic-related outcomes were observed
      according to the site of cancer. These findings suggest the development of cancer
      specific anticoagulant strategies as an area for further research.

PMID- 27884654
TI  - A narrative review of interventions addressing the parental-fetal relationship.
AB  - BACKGROUND: Expectant parents develop varying degrees of emotional affiliation
      with the unborn child. Interventions supporting this relationship may be
      beneficial given its link to maternal health behaviour during pregnancy, as well
      as the parental-infant bond after birth. AIM: To identify and describe the
      effects of programmes and strategies that have addressed the parental-fetal
      relationship. METHOD: English-language primary studies, published between 2005
      2015, were identified and their methodological quality was assessed. Databases
      used included CINAHL, Cochrane Library, MEDLINE, PsycINFO and Web of Science. Key
      search terms included maternal/paternal-fetal attachment, prenatal bond, parental
      fetal relationship and intervention. RCTs, non-RCTs, observational and non
      comparative studies, before and after studies and case studies were included.
      FINDINGS: Twenty-seven papers were included. Studies evaluated the effects of
      various strategies, including ultrasound and screening procedures, fetal
      awareness interventions, social and psychological support techniques, educational
      programmes and relaxation strategies. Results are inconsistent due to the
      diversity of interventions and significant variation in methodological quality.
      CONCLUSION: There is insufficient evidence to support definitive conclusions
      regarding the efficacy of any included intervention. A number of limitations,
      such as non-probability sampling, lack of blinding, and insufficient follow-up
      weaken the evidence. The inclusion of fathers in only three studies reflects the
      overall neglect of men in research regarding the prenatal relationship. Further
      in-depth study of the nature of the maternal/paternal-fetal relationship may be
      needed in order to allow for the identification of interventions that are
      consistently beneficial and worthwhile.

PMID- 27884656
TI  - Evaluating Complement-Mediated Humoral Immunity to P. falciparum Blood Stages.

PMID- 27884658
TI  - Could an automated machine replace the pharmacist?

PMID- 27884657
TI  - The origin and diversification of the developmental mechanisms that pattern the
      vertebrate head skeleton.
AB  - The apparent evolvability of the vertebrate head skeleton has allowed a diverse
      array of shapes, sizes, and compositions of the head in order to better adapt
      species to their environments. This encompasses feeding, breathing, sensing, and
      communicating: the head skeleton somehow participated in the evolution of all
      these critical processes for the last 500 million years. Through evolution,
      present head diversity was made possible via developmental modifications to the
      first head skeletal genetic program. Understanding the development of the
      vertebrate common ancestor's head skeleton is thus an important step in
      identifying how different lineages have respectively achieved their many
      innovations in the head. To this end, cyclostomes (jawless vertebrates) are
      extremely useful, having diverged from jawed vertebrates approximately 400
      million years ago, at the deepest node within living vertebrates. From this
      ancestral vantage point (that is, the node connecting cyclostomes and
      gnathostomes) we can best identify the earliest major differences in development
      between vertebrate classes, and start to address how these might translate onto
      morphology. In this review we survey what is currently known about the cell
      biology and gene expression during head development in modern vertebrates,
      allowing us to better characterize the developmental genetics driving head
      skeleton formation in the most recent common ancestor of all living vertebrates.
      By pairing this vertebrate composite with information from fossil chordates, we
      can also deduce how gene regulatory modules might have been arranged in the
      ancestral vertebrate head. Together, we can immediately begin to understand which
      aspects of head skeletal development are the most conserved, and which are
      divergent, informing us as to when the first differences appear during
      development, and thus which pathways or cell types might be involved in
      generating lineage specific shape and structure.

PMID- 27884659
TI  - Relationship between plasma glycation with membrane modification, oxidative
      stress and expression of glucose trasporter-1 in type 2 diabetes patients with
      vascular complications.
AB  - BACKGROUND OF STUDY: Enhanced protein glycation in diabetes causes irreversible
      cellular damage through membrane modifications. Erythrocytes are persistently
      exposed to plasma glycated proteins; however, little are known about its
      consequences on membrane. Aim of this study was to examine the relationship
      between plasma protein glycation with erythrocyte membrane modifications in type
      2 diabetes patients with and without vascular complications. METHOD: We recruited
      60 healthy controls, 85 type 2 diabetic mellitus (DM) and 75 type 2 diabetic
      patients with complications (DMC). Levels of plasma glycation adduct with
      antioxidants (fructosamine, protein carbonyl, beta-amyloids, thiol groups, total
      antioxidant status), erythrocyte membrane modifications (protein carbonyls, beta
      amyloids, free amino groups, erythrocyte fragility), antioxidant profile (GSH,
      catalase, lipid peroxidation) and Glut-1 expression were quantified. RESULT:
      Compared with controls, DM and DMC patients had significantly higher level of
      glycation adducts, erythrocyte fragility, lipid peroxidation and Glut-1
      expression whereas declined levels of plasma and cellular antioxidants.
      Correlation studies revealed positive association of membrane modifications with
      erythrocyte sedimentation rate, fragility, peroxidation whereas negative
      association with free amino groups, glutathione and catalase. CONCLUSION: Our
      data suggest that plasma glycation is associated with oxidative stress, Glut-1
      expression and erythrocyte fragility in DM patients. This may further contribute
      to progression of vascular complications.

PMID- 27884655
TI  - Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating
      Disseminated Infection with Multi-organ Involvement Including Orchitis
      Effectively Treated by Recombinant Type I Interferons.
AB  - BACKGROUND: Disseminated or fatal Zika virus (ZIKV) infections were reported in
      immunosuppressed patients. Existing interferon-signaling/receptor-deficient mouse
      models may not be suitable for evaluating treatment effects of recombinant
      interferons. METHODS: We developed a novel mouse model for ZIKV infection by
      immunosuppressing BALB/c mice with dexamethasone. RESULTS: Dexamethasone
      immunosuppressed male mice (6-8weeks) developed disseminated infection as
      evidenced by the detection of ZIKV-NS1 protein expression and high viral loads in
      multiple organs. They had >=10% weight loss and high clinical scores soon after
      dexamethasone withdrawal (10dpi), which warranted euthanasia at 12dpi. Viral
      loads in blood and most tissues at 5dpi were significantly higher than those at
      12dpi (P<0.05). Histological examination revealed prominent inflammatory
      infiltrates in multiple organs, and CD45+ and CD8+ inflammatory cells were seen
      in the testis. These findings suggested that clinical deterioration occurred
      during viral clearance by host immune response. Type I interferon treatments
      improved clinical outcome of mice (100% vs 0% survival). CONCLUSIONS: Besides
      virus dissemination, inflammation of various tissues, especially orchitis, may be
      potential complications of ZIKV infection with significant implications on
      disease transmission and male fertility. Interferon treatment should be
      considered in patients at high risks for ZIKV-associated complications when the
      potential benefits outweigh the side effects of treatment.

PMID- 27884661
TI  - Association of kidney disease measures with risk of renal function worsening in
      patients with hypertension and type 2 diabetes.
AB  - AIMS: To assess the role of kidney disease measures on the development of chronic
      kidney disease (CKD) in patients with type 2 diabetes (T2D) and hypertension
      (HT). METHODS: Clinical records from a total of 17,160 patients with T2D and HT,
      a baseline estimated glomerular filtration rate (eGFR) values >=60mL/min/1.73m2,
      evaluation for albuminuria and regular visits during a four-year follow-up were
      retrieved and analyzed. The incidence of eGFR <60mL/min/1.73m2 and/or a reduction
      >30% from baseline was evaluated. RESULTS: At baseline 23% of patients (n=3873)
      had albuminuria. Over the 4-year follow-up 20% (n=3480) developed a renal
      endpoint 28% (n=1074) of those with albuminuria and 17% (n=2406) of those without
      albuminuria. The presence of baseline albuminuria entailed a 1.8 independent,
      greater risk of reaching stage 3 CKD. Patients with normal albuminuria showed a
      1.54 (p<0.001) greater risk for each 5mL reduction (below 90mL/min) in baseline
      GFR. CONCLUSIONS: In T2D patients with HT, eGFR reduction and albuminuria are
      independently associated with a greater risk of developing stage 3 CKD. While
      baseline albuminuria entails a greater renal risk, due to a larger occurrence of
      the non-albuminuric phenotype, renal function worsening is more likely to be
      observed in patients without albuminuria.

PMID- 27884662
TI  - Integrity of central nervous function in diabetes mellitus assessed by resting
      state EEG frequency analysis and source localization.
AB  - Diabetes mellitus (DM) is associated with structural and functional changes of
      the central nervous system. We used electroencephalography (EEG) to assess
      resting state cortical activity and explored associations to relevant clinical
      features. Multichannel resting state EEG was recorded in 27 healthy controls and
      24 patients with longstanding DM and signs of autonomic dysfunction. The power
      distribution based on wavelet analysis was summarized into frequency bands with
      corresponding topographic mapping. Source localization analysis was applied to
      explore the electrical cortical sources underlying the EEG. Compared to controls,
      DM patients had an overall decreased EEG power in the delta (1-4Hz) and gamma (30
      45Hz) bands. Topographic analysis revealed that these changes were confined to
      the frontal region for the delta band and to central cortical areas for the gamma
      band. Source localization analysis identified sources with reduced activity in
      the left postcentral gyrus for the gamma band and in right superior parietal
      lobule for the alpha1 (8-10Hz) band. DM patients with clinical signs of autonomic
      dysfunction and gastrointestinal symptoms had evidence of altered resting state
      cortical processing. This may reflect metabolic, vascular or neuronal changes
      associated with diabetes.

PMID- 27884660
TI  - Exenatide improves diastolic function and attenuates arterial stiffness but does
      not alter exercise capacity in individuals with type 2 diabetes.
AB  - BACKGROUND: Exercise is recommended as a cornerstone of treatment for type 2
      diabetes mellitus (T2DM), however, it is often poorly adopted by patients. Even
      in the absence of apparent cardiovascular disease, persons with T2DM have an
      impaired ability to carry out maximal and submaximal exercise and these
      impairments are correlated with cardiac and endothelial dysfunction. Glucagon
      like pepetide-1 (GLP-1) augments endothelial and cardiac function in T2DM. We
      hypothesized that administration of a GLP-1 agonist (exenatide) would improve
      exercise capacity in T2DM. METHODS AND RESULTS: Twenty-three participants (64+/
      4years; mean+/-SE) with uncomplicated T2DM were randomized in a double-blinded
      manner to receive either 10MUg BID of exenatide or matching placebo after
      baseline measurements. Treatment with exenatide did not improve VO2peak
      (P=0.1464) or VO2 kinetics (P=0.2775). Diastolic function, assessed via resting
      lateral E:E', was improved with administration of exenatide compared with placebo
      (Placebo Pre: 7.6+/-1.0 vs. Post: 8.4+/-1.2 vs. Exenatide Pre: 8.1+/-0.7 vs.
      Post: 6.7+/-0.6; P=0.0127). Additionally, arterial stiffness measured by pulse
      wave velocity, was reduced with exenatide treatment compared with placebo
      (Placebo Pre: 10.5+/-0.8 vs. Post: 11.5+/-1.1s vs. Exenatide Pre: 11.4+/-1.8 vs.
      Post: 10.2+/-1.4s; P=0.0373). Exenatide treatment did not improve endothelial
      function (P=0.1793). CONCLUSIONS: Administration of exenatide improved cardiac
      function and reduced arterial stiffness, however, these changes were not
      accompanied by improved functional exercise capacity. In order to realize the
      benefits of this drug on exercise capacity, combining exenatide with aerobic
      exercise training in participants with T2DM may be warranted.

PMID- 27884664
TI  - Bacterial contamination of saline used for epidural procedures in an obstetric
      setting: a randomised comparison of two drawing-up techniques.
AB  - BACKGROUND: There is little evidence to inform practice regarding the optimum
      aseptic technique of drawing up saline for epidural insertion. Our regional
      practice is to draw up saline from a non-sterile packaged plastic ampoule,
      therefore introducing the risk of bacterial contamination. Usually, the
      anaesthetist draws up saline directly from the vial held by an assistant using a
      needle (needle technique). Alternatively, the saline vial is emptied onto a
      sterile tray by an assistant and then drawn up by the anaesthetist (tray
      technique). We hypothesised that the latter will lead to an increase in the
      number of contaminated saline samples as they are exposed to the environment.
      METHODS: In labour rooms and before epidural catheter insertion, 110 samples of
      saline 20mL were randomly drawn up using our hospital's recommended epidural
      aseptic precautions, using either the needle or the tray technique. Equal amounts
      of saline were inoculated into aerobic and anaerobic blood culture bottles.
      RESULTS: Eleven percent of samples in the needle arm and 24% of samples in the
      tray arm grew commensal micro-organisms including coagulase-negative
      Staphylococcus, Micrococcus luteus and Streptococcus viridans. A two-sided
      Fisher's exact test for categorical unpaired data showed no statistical
      difference between the two arms of the trial (P=0.13). CONCLUSION: The difference
      in the saline contamination rate between the two techniques did not reach
      statistical significance. As bacterial contamination occurred with both
      techniques, we recommend using sterile saline pre-packaged in the epidural tray
      or individually wrapped sterile glass saline ampoules.

PMID- 27884663
TI  - Early impairment in left ventricular longitudinal systolic function is associated
      with an increased risk of incident atrial fibrillation in patients with type 2
      diabetes.
AB  - AIMS: It is known that type 2 diabetic patients are at high risk of atrial
      fibrillation (AF). However, the early echocardiographic determinants of AF
      vulnerability in this patient population remain poorly known. METHODS: We
      followed-up for 2years a sample of 180 consecutive outpatients with type 2
      diabetes, who were free from AF and ischemic heart disease at baseline. All
      patients underwent a baseline echocardiographic-Doppler evaluation with tissue
      Doppler and 2-D strain analysis. Standard electrocardiograms were performed twice
      per year, and a diagnosis of incident AF was confirmed in affected patients by a
      single cardiologist. RESULTS: Over the 2-year follow-up period, 14 (7.8%)
      patients developed incident AF. In univariate analyses, echocardiographic
      predictors of new-onset AF were greater indexed cardiac mass, larger indexed left
      atrial volume (LAVI), lower global longitudinal strain (LSSYS), lower global
      diastolic strain rate during early phase of diastole (SRE), lower global
      diastolic strain rate during late phase of diastole (SRL), and higher E/SRE
      ratio. Multivariate logistic regression analysis showed that lower LSSYS remained
      the only significant predictor of new-onset AF (adjusted-odds ratio 1.63, 95%CI
      1.17-2.27; p<0.005) after adjustment for age, sex, diabetes duration, indexed
      cardiac mass and LAVI. Results were unchanged even after adjustment for body mass
      index, hypertension and glycemic control. CONCLUSIONS: This is the first
      prospective study to show that early LSSYS impairment independently predicts the
      risk of new-onset AF in type 2 diabetic patients with preserved ejection fraction
      and without ischemic heart disease. Future larger prospective studies are needed
      to confirm these findings.

PMID- 27884665
TI  - Airway management for cesarean delivery performed under general anesthesia.
AB  - BACKGROUND: With the increasing popularity of neuraxial anesthesia, there has
      been a decline in the use of general anesthesia for cesarean delivery. We sought
      to examine the incidence, outcome and characteristics associated with a failed
      airway in patients undergoing cesarean delivery under general anesthesia.
      METHODS: A retrospective review of airway management in women undergoing cesarean
      delivery under general anesthesia over an eight-year period from 2006-2013 at an
      academic medical center was conducted. RESULTS: During the study period, 10 077
      cesarean deliveries were performed. Neuraxial anesthesia was used in 9382 (93%)
      women while general anesthesia was used in 695 (7%). Emergent cesarean delivery
      was the most common indication for general anesthesia. Failed intubation was
      encountered in only three (0.4%) women, who were successfully managed with a
      laryngeal mask airway. The overall incidence of failed intubation was 1 in 232
      (95% CI 1:83 to 1:666) and general anesthesia was continued in all cases. There
      were no adverse maternal or fetal outcomes directly related to failed intubation.
      CONCLUSION: Advances in adjunct airway equipment, availability of an experienced
      anesthesiologist and simulation-based teaching of failed airway management in
      obstetrics may have contributed to our improved maternal outcomes in patients
      undergoing cesarean delivery under general anesthesia.

PMID- 27884667
TI  - Persistent pain after caesarean section and its association with maternal anxiety
      and socioeconomic background.
AB  - BACKGROUND: Pain, both from the surgical site, and from other sources such as
      musculoskeletal backache, can persist after caesarean section. In this study of a
      predominantly socially deprived population we have sought to prospectively
      examine the association between antenatal maternal anxiety and socioeconomic
      background and the development of persistent pain of all sources after caesarean
      section. METHODS: Demographic details and an anxiety questionnaire were completed
      by 205 women before elective caesarean section. On the first postoperative day,
      pain scores were recorded, and at four months patients were asked to complete a
      Brief Pain Inventory and an Edinburgh Postnatal Depression Score. RESULTS: Of 205
      parturients recruited, 186 records were complete at the hospital admission phase
      and 98 (52.7%) were complete at the four-month follow-up phase. At recruitment,
      15.1% reported pain. At four months 41.8% (95% CI 32.1 to 51.6%) reported pain,
      of whom pain was a new finding in 35.7% (95% CI 26.2 to 45.2%). Antenatal anxiety
      was not a significant predictor of severity of new pain at four months (P=0.44
      for state anxiety, P=0.52 for trait anxiety). However, four-month pain severity
      did correlate with social deprivation (P=0.011), postnatal depression (P<0.001)
      and pain at 24h (P=0.018). CONCLUSION: Persistent pain from a variety of sources
      after caesarean section is common. Our findings do not support the use of
      antenatal anxiety scoring to predict persistent pain in this setting, but suggest
      that persistent pain is influenced by acute pain, postnatal depression and
      socioeconomic deprivation.

PMID- 27884668
TI  - Noise in the obstetric operating room.

PMID- 27884666
TI  - Anesthetic considerations in a parturient with congenital insensitivity to pain
      with anhidrosis.
AB  - Congenital insensitivity to pain is a rare autosomal recessive disease
      characterized by varying degrees of autonomic dysfunction and sensory loss,
      including nociceptive hyposensitivity. It is this autonomic dysfunction that
      makes both general and neuraxial anesthesia challenging. Testing the block during
      neuraxial anesthesia may be difficult and the patient may be prone to hypotension
      and bradycardia. This case report describes the anesthetic management of a
      parturient with congenital insensitivity to pain presenting for cesarean
      delivery.

PMID- 27884669
TI  - Grafting of aniline derivatives onto chitosan and their applications for removal
      of reactive dyes from industrial effluents.
AB  - A series of chitosan-grafted polyaniline derivatives {chitosan-g-polyaniline (CS
      g-PANI), chitosan-g-poly(N-methylaniline) (CS-g-PNMANI), and chitosan-g-poly(N
      ethylaniline) (CS-g-PNEANI)} were synthesized by in situ chemical oxidation
      polymerization method. The synthesized copolymers were analyzed by means of
      Fourier transform infrared (FTIR), and ultraviolet-visible (UV-vis)
      spectroscopies, thermogravimetric analysis (TGA), and field emission scanning
      electron microscopy (FE-SEM). These copolymers were applied as adsorbent for
      removal of acid red 4 (AR4) and direct red 23 (DR23) from aqueous solutions. The
      adsorption processes were optimized in terms of pH, adsorbent amount, and dyes
      concentrations. The maximum adsorption capacities (Qm) for the synthesized
      copolymers were calculated, and among them the CS-g-PNEANI sample showed highest
      Qm for both AR4 (98mgg-1) and DR23 (112mgg-1) dyes. The adsorption kinetics of
      AR4 and DR23 dyes follow the pseudo-second order kinetic model. The regeneration
      and reusability tests revealed that the synthesized adsorbents had the relatively
      good reusability after five repetitions of the adsorption-desorption cycles. As
      the results, it is expected that the CS-g-PANIs find application for removal of
      reactive dyes (especially anionic dyes) from industrial effluents mainly due to
      their low production costs and high adsorption effectiveness.

PMID- 27884670
TI  - Preparation of ecofriendly UV-protective food packaging material by starch/TiO2
      bio-nanocomposite: Characterization.
AB  - In this study, ecofriendly starch/TiO2 bio-nanocomposites were produced using
      with different nano-TiO2 (TiO2) content (1, 3, and 5 (wt%)). Physical,
      mechanical, thermal, water-vapor permeability (WVP) properties and UV
      transmittance were investigated. Our results showed that the increasing TiO2
      content increased the hydrophobicity of starch/TiO2 films. WVP of the bio
      nanocomposites was reduced, simultaneously. With increasing TiO2 content, tensile
      strength and Young's modulus of the film specimens were reduced while elongation
      at break and tensile energy to break were increased. The thermal properties of
      specimens showed that glass transition temperature of the films increased but
      melting point of the specimen films was decreased by increasing TiO2 content.
      Scanning electron microscopy observations demonstrated, the most of films'
      physical properties were in relation to their microstructures. The starch/TiO2
      nanocomposites effectively protect goods against UV light, and could potentially
      be applied as UV-shielding packaging materials.

PMID- 27884671
TI  - Anti-tumor and immunomodulatory activities induced by an alkali-extracted
      polysaccharide BCAP-1 from Bupleurum chinense via NF-kappaB signaling pathway.
AB  - Bupleurum chinense is a well-known traditional Chinese medicine. Polysaccharides
      extracted from medical plants possess multiple healthy benefits. In the present
      study, an alkali-extracted polysaccharide (BCAP-1) was isolated from Bupleurum
      chinense, and evaluated its physicochemical features, anti-tumor activities and
      immunomodulatory effects. BCAP-1 was obtained by alkali-extraction, ethanol
      precipitation, and fractionation by DEAE-cellulose and Sepharose CL-6B columns.
      BCAP-1 markedly inhibited Sarcoma 180tumor growth in tumor-bearing mice, and
      increased the secretion of TNF-alpha in serum. MTT assay showed that BCAP-1 had
      no cytotoxicity against S-180 tumor cells. BCAP-1 enhanced the secretion of TNF
      alpha and NO, and the transcripts of TNF-alpha and iNOS were increased.
      Meanwhile, BCAP-1 treatment induced the phosphorylation of p65 and decreased the
      expression of IkappaB in macrophages. These results suggest that BCAP-1 could
      activate macrophages through NF-kappaB signaling pathway, and the anti-tumor
      effects of BCAP-1 can be achieved by its immunostimulating features.

PMID- 27884672
TI  - Spectroscopic study on the binding of chelerythrine with duplex poly (rA): A
      model of RNA intercalation.
AB  - Here we have reported a detail study on the interaction of the
      benzophenanthridine alkaloid chelerythrine (CHL) with double stranded
      polyriboadenylic acid [ds poly (rA)] by exploiting various spectroscopic
      techniques. The alkaloid shows high binding affinity (binding constant is
      1.10*105M-1) towards the double stranded RNA as revealed from Scatchard plot. The
      binding was confirmed by hypochromic effect in the UV-vis spectrum of CHL,
      increase in fluorescence intensity of CHL and perturbations of the circular
      dichroism (CD) spectrum of ds poly (rA). Later fluorescence quenching,
      cooperative CD melting transition, viscometric and molecular modeling studies
      establish the fact that the alkaloid binds to the ds poly (rA) by the mechanism
      of intercalation. Thermodynamic parameters obtained from the isothermal titration
      calorimetric (ITC) study show that the binding is favoured by negative enthalpy
      and small positive entropy changes. This report may be a model for intercalation
      of small molecule like CHL to the double stranded RNA.

PMID- 27884673
TI  - Fabrication and characterization of chitosan-crosslinked-poly(alginic acid)
      nanohydrogel for adsorptive removal of Cr(VI) metal ion from aqueous medium.
AB  - In this study, chitosan-crosslinked-poly (alginic acid) nanohydrogel (CN-cl
      PL(AA)NHG) was synthesized by co-polymerization method. It was used an effective
      adsorbent for the exclusion of Cr(VI) metal ion from aqueous medium. The
      synthesized nanohydrogel was characterized by FTIR, SEM and TEM. The TEM images
      clearly indicated the appearance of smooth surface with average size of particles
      ranging from 30 to 80nm. The effect of different adsorption parameters like
      agitation time, temperature, initial metal ion concentration and adsorbent dosage
      was studied and optimized. The results demonstrated that the prepared chitosan
      crosslinked-poly (alginic acid) nanohydrogel had high adsorption tendency for the
      removal of Cr(VI) from the aqueous solution. The pseudo-second-order equation
      represented the better adsorption kinetics for the adsorption process. The
      thermodynamic studies showed the adsorption of Cr(VI) onto CN-cl-PL(AA)NHG was
      spontaneous and chemical in nature.

PMID- 27884674
TI  - Modification of foxtail millet starch by combining physical, chemical and
      enzymatic methods.
AB  - Modification of foxtail millet starch was carried out by heat moisture treatment
      (HT), acid hydrolysis (AH), enzymatic treatment (EH), Ultrasound treatment (UT)
      and their combinations. A total of 15 modified starches were prepared by
      combining the various methods and properties were compared with native starch.
      The solubilities of the starches modified by HT were found to decrease whereas
      for other single modifications it increased. It also increased with number of
      modifications applied. The swelling power decreased for all the modified starches
      and a decrease in swelling power was observed with increase in number of
      modifications. Freeze-thaw stability improved for starches modified by single
      physical modifications i.e. HT and UT. Decrease in viscosities was observed for
      the modified starches and was particularly affected by AH. The pasting
      temperature was found to increase for those modified starches where HT was
      carried out. The modified starches gave softer gels.

PMID- 27884675
TI  - Molecular cloning and functional analysis of squalene synthase (SS) in Panax
      notoginseng.
AB  - Panax notoginseng (Burk.) F. H. Chen, which is a used traditional Chinese
      medicine known as Sanqi or Tianqi in China, is widely studied for its ability to
      accumulate the triterpene saponins. Squalene synthase (SS: EC 2.5.1.21) catalyzes
      the first enzymatic step from the central isoprenoid pathway toward sterol and
      triterpenoid biosynthesis. In this study, SS from P. notoginseng was cloned and
      investigated followed by its recombinant expression and preliminary enzyme
      activity. The nucleotide sequence of the ORF contains 1 248 nucleotides and
      encodes 415 amino acid residues with molecular weight of 47.16kDa and pI of 6.50.
      Bioinformatics analysis revealed that the deduced PnSS protein had a high
      similarity with other plant squalene synthases. To obtain soluble recombinant
      enzymes, 29 hydrophobic amino acids were deleted from the carboxy terminus and
      expressed as GST-Tag fusion protein in Escherichia coli BL21 (DE3). Approximately
      66.46kDa recombinant protein was checked on SDS-PAGE and Western Blot analysis.
      Preliminary activity of the resultant bacterial crude extract was analyzed by gas
      chromatograph-mass spectrometer (GC-MS). The identification and function of PnSS
      is important for further studies of the triterpene saponins biosynthesis in P.
      notoginseng.

PMID- 27884676
TI  - Protein interactions with silver nanoparticles: Green synthesis, and biophysical
      approach.
AB  - Silver nanoparticles (AgNPs) with an average particle size of 20nm were
      synthesized by using aromatic amino acid fluorescence active, tryptophan as a
      reducing agent. This study aims to investigate the interaction between Bovine
      Serum Albumin (BSA) and AgNPs as a function of particle size and shape. UV-vis
      analysis implies the formation of the ground state complex between BSA and AgNPs
      through electrostatic interactions. The fluorescence spectra indicated that the
      AgNPs have a potent ability to quench the intrinsic fluorescence of BSA by static
      quenching mechanisms. The different parameters (the apparent association constant
      (Kapp=2.6*104mol-1dm3), Stern-Volmer quenching constant (KSV=3.5*104mol-1dm3),
      number of binding sites (n=1.3) and bimolecular rate constant of the quenching
      reaction (kq=6.1*1012mol-1dm3s-1)) were calculated by using the UV-vis and
      fluorescence spectra and discussed. The indole moieties of tryptophan residues of
      BSA were responsible to the complex formation with AgNPs in ground and excited
      states via electrostatic, van der Waals, hydrogen bonding, hydrophobic and
      hydrophilic interactions. Adsorption of AgNPs into the core of BSA changes the
      tryptophan environment from hydrophobic to hydrophilic (from folding to partially
      folded and/or unfolded). Circular dichroism results suggested that the helicity
      of BSA decreased from 67.68% to 60.25% and 67.68% to 45.42% with [AgNPs] and
      temperature, respectively.

PMID- 27884677
TI  - Mastery-Based Virtual Reality Robotic Simulation Curriculum: The First Step
      Toward Operative Robotic Proficiency.
AB  - OBJECTIVE: Hepatobiliary surgery is a highly complex, low-volume specialty with
      long learning curves necessary to achieve optimal outcomes. This creates
      significant challenges in both training and measuring surgical proficiency. We
      hypothesize that a virtual reality curriculum with mastery-based simulation is a
      valid tool to train fellows toward operative proficiency. This study evaluates
      the content and predictive validity of robotic simulation curriculum as a first
      step toward developing a comprehensive, proficiency-based pathway. DESIGN: A
      mastery-based simulation curriculum was performed in a virtual reality
      environment. A pretest/posttest experimental design used both virtual reality and
      inanimate environments to evaluate improvement. Participants self-reported
      previous robotic experience and assessed the curriculum by rating modules based
      on difficulty and utility. SETTING: This study was conducted at the University of
      Pittsburgh Medical Center (Pittsburgh, PA), a tertiary care academic teaching
      hospital. PARTICIPANTS: A total of 17 surgical oncology fellows enrolled in the
      curriculum, 16 (94%) completed. RESULTS: Of 16 fellows who completed the
      curriculum, 4 fellows (25%) achieved mastery on all 24 modules; on average,
      fellows mastered 86% of the modules. Following curriculum completion, individual
      test scores improved (p < 0.0001). An average of 2.4 attempts was necessary to
      master each module (range: 1-17). Median time spent completing the curriculum was
      4.2 hours (range: 1.1-6.6). Total 8 (50%) fellows continued practicing modules
      beyond mastery. Survey results show that "needle driving" and "endowrist 2"
      modules were perceived as most difficult although "needle driving" modules were
      most useful. Overall, 15 (94%) fellows perceived improvement in robotic skills
      after completing the curriculum. CONCLUSIONS: In a cohort of board-certified
      general surgeons who are novices in robotic surgery, a mastery-based simulation
      curriculum demonstrated internal validity with overall score improvement. Time to
      complete the curriculum was manageable.

PMID- 27884678
TI  - A common global risk stratification system for hepatoblastoma.

PMID- 27884680
TI  - Caloric restriction ameliorates cardiomyopathy in animal model of diabetes.
AB  - BACKGROUND: The db/db mouse is an animal model of diabetes in which leptin
      receptor activity is deficient resulting accelerated cardiomyopathy when exposed
      to angiotensin (AT). Toll-like receptors 4 and 2 (TLR4, TLR2) are pattern
      recognition receptors, that recognize pathogen-associated molecular patterns and
      exacerbate and release inflammatory cytokines. Fetuin A (Fet A) is a fatty acid
      carrier which affects inflammation and insulin resistance in obese humans and
      animals through TLRs. The aim of this study was to investigate the effect of
      caloric restriction (CR) on free fatty acids (FFA) level and the inflammatory
      response in diabetic cardiomyopathy. METHODS AND RESULTS: Left ventricular
      hypertrophy, increased fibrosis and leukocytes infiltration were observed in
      db/db AT treated hearts. Serum glucose, FFA, and cholesterol levels were elevated
      in db/db AT treated mice. Cardiac expression of PPARalpha increased while AKT
      phosphorylation was decreased. CONCLUSIONS: Cumulatively, CR elevated cardiac
      PPARalpha improved the utilization of fatty acids, and reduced myocardial
      inflammation as seen by reduced levels of Fet A. Thus CR negated cardiomyopathy
      associated with AT in an animal model of diabetes suggesting that CR is an
      effective therapeutic approach in the treatment of diabetes and associated
      cardiomyopathy.

PMID- 27884679
TI  - Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the
      Children's Hepatic tumors International Collaboration.
AB  - BACKGROUND: Comparative assessment of treatment results in paediatric
      hepatoblastoma trials has been hampered by small patient numbers and the use of
      multiple disparate staging systems by the four major trial groups. To address
      this challenge, we formed a global coalition, the Children's Hepatic tumors
      International Collaboration (CHIC), with the aim of creating a common approach to
      staging and risk stratification in this rare cancer. METHODS: The CHIC steering
      committee-consisting of leadership from the four major cooperative trial groups
      (the International Childhood Liver Tumours Strategy Group, Children's Oncology
      Group, the German Society for Paediatric Oncology and Haematology, and the
      Japanese Study Group for Paediatric Liver Tumours)-created a shared international
      database that includes comprehensive data from 1605 children treated in eight
      multicentre hepatoblastoma trials over 25 years. Diagnostic factors found to be
      most prognostic on initial analysis were PRETreatment EXTent of disease (PRETEXT)
      group; age younger than 3 years, 3-7 years, and 8 years or older; alpha
      fetoprotein (AFP) concentration of 100 ng/mL or lower and 101-1000 ng/mL; and the
      PRETEXT annotation factors metastatic disease (M), macrovascular involvement of
      all hepatic veins (V) or portal bifurcation (P), contiguous extrahepatic tumour
      (E), multifocal tumour (F), and spontaneous rupture (R). We defined five
      clinically relevant backbone groups on the basis of established prognostic
      factors: PRETEXT I/II, PRETEXT III, PRETEXT IV, metastatic disease, and AFP
      concentration of 100 ng/mL or lower at diagnosis. We then carried the additional
      factors into a hierarchical backwards elimination multivariable analysis and used
      the results to create a new international staging system. RESULTS: Within each
      backbone group, we identified constellations of factors that were most predictive
      of outcome in that group. The robustness of candidate models was then
      interrogated using the bootstrapping procedure. Using the clinically established
      PRETEXT groups I, II, III, and IV as our stems, we created risk stratification
      trees based on 5 year event-free survival and clinical applicability. We defined
      and adopted four risk groups: very low, low, intermediate, and high.
      INTERPRETATION: We have created a unified global approach to risk stratification
      in children with hepatoblastoma on the basis of rigorous statistical
      interrogation of what is, to the best of our knowledge, the largest dataset ever
      assembled for this rare paediatric tumour. This achievement provides the
      structural framework for further collaboration and prospective international
      cooperative study, such as the Paediatric Hepatic International Tumour Trial
      (PHITT). FUNDING: European Network for Cancer Research in Children and
      Adolescents, funded through the Framework Program 7 of the European Commission
      (grant number 261474); Children's Oncology Group CureSearch grant contributed by
      the Hepatoblastoma Foundation; Practical Research for Innovative Cancer Control
      and Project Promoting Clinical Trials for Development of New Drugs and Medical
      Devices, Japan Agency for Medical Research; and Swiss Cancer Research grant.

PMID- 27884682
TI  - Sleep & metabolism: The multitasking ability of lateral hypothalamic inhibitory
      circuitries.
AB  - The anatomical and functional mapping of lateral hypothalamic circuits has been
      limited by the numerous cell types and complex, yet unclear, connectivity. Recent
      advances in functional dissection of input-output neurons in the lateral
      hypothalamus have identified subset of inhibitory cells as crucial modulators of
      both sleep-wake states and metabolism. Here, we summarize these recent studies
      and discuss the multi-tasking functions of hypothalamic circuitries in
      integrating sleep and metabolism in the mammalian brain.

PMID- 27884681
TI  - Acidic stress induced G1 cell cycle arrest and intrinsic apoptotic pathway in
      Jurkat T-lymphocytes.
AB  - BACKGROUND: Low extracellular pH (pHe) is a common hallmark of tumor
      microenvironment, which will also affect pH sensitive T-lymphocytes in this
      environment. Due to the growing interest on T-cell mediated cancer therapies,
      acidic stress induced consequences on this lymphocyte deserves through
      investigations. RESULTS: In line with our previous study [Kim et al., Biochem.
      Biophys. Res. Commun. 2016; 472(4): 585-91.], we applied sub-lethal acidic stress
      (pH 3.3, 37 degrees C for 25min) to Jurkat T-lymphocytes. Progression from early
      apoptosis into late apoptosis was clearly observed by flow cytometry within 3
      days. Treatment led to onset of G1 arrest in the first 24h and cell cycling data
      corresponded to survival of an invasive alkaline phosphatase (AP) positive
      population. Concerning the massive cell death observed after 72h, both mRNA level
      (qRT-PCR) and protein level (western blotting) data indicate programmed cell
      death through p53-p21 independent signaling. CONCLUSION: Taken together, the
      results obtained suggest that the majority of Jurkat cells exposed to short but
      intense acidic stress conditions, as used here, undergo intrinsic apoptosis,
      while invasion and AP activation only occurred in a small surviving cell
      population.

PMID- 27884683
TI  - Yttrium-90 Radioembolization with Resin Microspheres without Routine Embolization
      of the Gastroduodenal Artery.
AB  - PURPOSE: To evaluate safety of resin microsphere radioembolization (RE) without
      prophylactic embolization of the gastroduodenal artery (GDA). MATERIALS AND
      METHODS: Between July 2013 and April 2015, all patients undergoing RE with resin
      microspheres for liver-dominant metastatic disease were treated without routine
      embolization of the GDA. Selective embolization of distal hepaticoenteric vessels
      was performed if identified by digital subtraction angiography, cone-beam
      computed tomography, or technetium-99m macroaggregated albumin scintigraphy.
      Resin microspheres were administered using 5% dextrose flush distal to the origin
      of the GDA in lobar or segmental fashion, with judicious use of an antireflux
      microcatheter in recognized high-risk situations. Gastrointestinal toxicity was
      evaluated by the performing physician for at least 3 months. RESULTS: RE with
      resin microspheres was performed in 62 patients undergoing 69 treatments. During
      planning angiography, embolization of 0 or 1 vessel (median, 1; range, 0-4) was
      performed in 86% of patients, most commonly the right gastric and supraduodenal
      arteries. Prophylactic embolization of the GDA was performed in only 2 patients
      (3%). In 6 treatments (9%), adjunctive embolization was required immediately
      before RE, and an antireflux microcatheter was used in 14% of treatments.
      Clinical follow-up was available in 60 of 62 patients (median, 134 d; range, 15
      582 d). No signs or symptoms of gastric or duodenal ulceration were observed.
      CONCLUSIONS: RE using resin microspheres without embolization of the GDA can be
      performed safely.

PMID- 27884684
TI  - Factors Related to Late False Lumen Enlargement after Thoracic Stent-Graft
      Placement for Type B Aortic Dissection.
AB  - PURPOSE: To evaluate significant factors related to delayed aortic false lumen
      (FL) enlargement in patients who have undergone thoracic stent-graft placement
      for type B aortic dissection. MATERIALS AND METHODS: The study included 62
      patients (45 male, 17 female) aged 26-80 years (mean age, 58.1 y) who underwent
      thoracic endovascular aortic repair for type B aortic dissection at a single
      institution between January 2005 and May 2015. Mean age of aortic dissections was
      5.3 months (range, 0.1-73.3 mo). Maximum aortic diameter at presentation was 41.7
      mm +/- 8.3. The follow-up period ranged from 3 to 104 months (mean, 27.1 mo).
      Computed tomographic (CT) angiography studies were reviewed to identify FL
      diameter enlargements > 5 mm at different levels along and distal to the stent
      graft. Imaging findings and clinical variables were investigated to determine
      their correlation with FL enlargement. RESULTS: No significant difference was
      found between the ages of aortic dissections in patients with and without FL
      enlargement (P = .26). On follow-up CT angiography, 16 patients had 2 or more
      communication channels between the FL and the systemic circulation, 7 of whom
      showed FL enlargement > 5 mm (P = .007). Twenty-seven patients showed complete FL
      thrombosis, none of whom had FL enlargement (P < .001). CONCLUSIONS: Two or more
      communication channels between the FL and the systemic circulation represent a
      risk factor for FL enlargement regardless of the age of the dissection. Patients
      with thrombosis of the FL are less likely to experience FL enlargement.

PMID- 27884685
TI  - Bleeding Complications following Image-Guided Percutaneous Biopsies in Patients
      Taking Clopidogrel-A Retrospective Review.
AB  - PURPOSE: To report incidence of bleeding after image-guided percutaneous core
      needle biopsy performed in patients taking clopidogrel within 5 days. MATERIALS
      AND METHODS: This was a retrospective review of image-guided percutaneous core
      needle biopsies performed in patients with clopidogrel use within 5 days of the
      procedure between January 2002 and November 2014. Data including biopsy site,
      needle size, number of samples, and serum coagulation studies were collected.
      Routine follow-up of patients was performed 24-72 hours after biopsy. Major
      bleeding complications were defined as grade 3 or greater using Common
      Terminology Criteria for Adverse Events. There were 63 deep biopsies performed in
      63 patients with recent use of clopidogrel. Mean time of clopidogrel abstinence
      before biopsy was 2.9 days +/- 1.9 (median 3 days). Clopidogrel had been taken
      within 24 hours of the biopsy by 12 patients. There were 48 patients (76%) who
      also took aspirin within 5 days of the procedure. The most common procedure was
      liver biopsy (21/63; 33%), followed by lung (12/63; 19%),
      abdominal/pelvic/retroperitoneal mass (12/63; 19%), and renal (11/63; 17%)
      biopsies. RESULTS: A major bleeding complication (1/63; 1.6%) occurred after
      injury to an intercostal artery during lung biopsy, which was successfully
      treated with coil embolization. No minor bleeding complications were identified.
      CONCLUSIONS: In this study comprising a small number of patients undergoing
      various biopsy procedures, recent clopidogrel use was associated with a very low
      incidence of major bleeding.

PMID- 27884687
TI  - The Utility of Viscoelastic Testing in Patients Undergoing IR Procedures.
AB  - Whole-blood viscoelastic testing can identify patient-specific coagulation
      disturbances, allowing for targeted repletion of necessary coagulation factors
      and differentiation between coagulopathy and surgical bleeding that requires
      intervention. Viscoelastic testing complements standard coagulation tests and has
      been shown to decrease transfusion requirements and improve survival in bleeding
      patients. Viscoelastic testing also can be used to predict bleeding and improve
      the care of patients undergoing interventional radiology (IR) procedures.

PMID- 27884686
TI  - Intraarterial Lidocaine for Pain Control in Uterine Artery Embolization: A
      Prospective, Randomized Study.
AB  - PURPOSE: To assess efficacy of two different techniques of lidocaine injection in
      the uterine arteries to reduce pain following uterine artery embolization (UAE)
      for leiomyomas. MATERIALS AND METHODS: This prospective randomized single-blinded
      study was performed with 60 patients enrolled between November 2014 and December
      2015 equally randomized to 3 arms. Group A received 10 mL lidocaine 1% (100 mg)
      mixed with polyvinyl alcohol particles (355-500 MUm). Group B received the same
      dose of lidocaine injected after embolization. Group C was a control group. Pain
      was assessed on a 100-point visual analog scale at 4, 7, and 24 hours after the
      procedure. Narcotic agent dose to 24 hours was recorded. Outcomes were examined
      by analysis of variance and pairwise comparison. Leiomyoma infarction was
      assessed with magnetic resonance imaging 3 months after the procedure. RESULTS:
      Technical success rate of UAE was 100%. Mean pain score at 4 hours was
      significantly lower in the lidocaine groups (group A, 28.6; group B, 35.8)
      compared with the control group (59.4; P = .001). Pain scores at 7 and 24 hours
      were not statistically different among the 3 arms. The mean in-hospital narcotic
      agent dose was significantly lower in both lidocaine groups than in the control
      group (group A, 8.5 mg [P = .002]; group B, 11.1 mg [P = .03]; group C, 17.4 mg).
      There were no adverse events related to the use of lidocaine. The number of
      patients with complete infarction of leiomyomas at 3 months was significantly
      lower in group A at 38.9% (group B, 77.8%; group C, 75%; P = .0451). CONCLUSIONS:
      Lidocaine injected in the uterine arteries reduced postprocedural pain and
      narcotic agent dose after UAE. There were more cases of incomplete necrosis when
      lidocaine was mixed with the particles.

PMID- 27884688
TI  - Severe Pain in Veterans: The Effect of Age and Sex, and Comparisons With the
      General Population.
AB  - : This study provides national prevalence estimates of US military veterans with
      severe pain, and compares veterans with nonveterans of similar age and sex. Data
      used are from the 2010 to 2014 National Health Interview Survey on 67,696 adults
      who completed the Adult Functioning and Disability Supplement. Participants with
      severe pain were identified using a validated pain severity coding system
      imbedded in the National Health Interview Survey Adult Functioning and Disability
      Supplement. It was estimated that 65.5% of US military veterans reported pain in
      the previous 3 months, with 9.1% classified as having severe pain. Compared with
      veterans, fewer nonveterans reported any pain (56.4%) or severe pain (6.4%).
      Whereas veterans aged 18 to 39 years had significantly higher prevalence rates
      for severe pain (7.8%) than did similar-aged nonveterans (3.2%), veterans age 70
      years or older were less likely to report severe pain (7.1%) than nonveterans
      (9.6%). Male veterans (9.0%) were more likely to report severe pain than male
      nonveterans (4.7%); however, no statistically significant difference was seen
      between the 2 female groups. The prevalence of severe pain was significantly
      higher in veterans with back pain (21.6%), jaw pain (37.5%), severe headaches or
      migraine (26.4%), and neck pain (27.7%) than in nonveterans with these conditions
      (respectively: 16.7%, 22.9%, 15.9%, and 21.4%). Although veterans (43.6%) were
      more likely than nonveterans (31.5%) to have joint pain, no difference was seen
      in the prevalence of severe pain associated with this condition. PERSPECTIVE:
      Prevalence of severe pain, defined as that which occurs "most days" or "every
      day" and bothers the individual "a lot," is strikingly more common in veterans
      than in members of the general population, particularly in veterans who served
      during recent conflicts. Additional assistance may be necessary to help veterans
      cope with their pain.

PMID- 27884689
TI  - Demographic Predictors of Pain Sensitivity: Results From the OPPERA Study.
AB  - : The demographic factors of sex, age, and race/ethnicity are well recognized as
      relevant to pain sensitivity and clinical pain expression. Of these, sex
      differences have been the most frequently studied, and most of the literature
      describes greater pain sensitivity for women. The other 2 factors have been less
      frequently evaluated, and current literature is not definitive. Taking advantage
      of the large Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA)
      study cohort, we evaluated the association of sex, age, and self-reported race
      with 34 measures of pressure, mechanical, and thermal pain sensitivity
      encompassing threshold and suprathreshold perception. Women were significantly
      more pain-sensitive than men for 29 of 34 measures. Age effects were small, and
      only significant for 7 of 34 measures, however, the age range was limited (18-44
      years of age). Race/ethnicity differences varied across groups and pain
      assessment type. Non-Hispanic white individuals were less pain-sensitive than
      African-American (for 21 of 34 measures), Hispanic (19 of 34), and Asian (6 of
      34) individuals. No pain threshold measure showed significant racial differences,
      whereas several suprathreshold pain measures did. This suggests that racial
      differences are not related to tissue characteristics or inherent nociceptor
      sensitivity. Rather, the differences observed for suprathreshold pain ratings or
      tolerance are more likely related to differences in central nociceptive
      processing, including modulation imposed by cognitive, psychological, and/or
      affective factors. PERSPECTIVE: The influence of sex, age, and race/ethnicity on
      various aspects of pain sensitivity, encompassing threshold and suprathreshold
      measures and multiple stimulus modalities, allows for a more complete evaluation
      of the relevance of these demographic factors to acute pain perception.

PMID- 27884690
TI  - Conditioned Pain Modulation and Pressure Pain Sensitivity in the Adult Danish
      General Population: The DanFunD Study.
AB  - : Increased pressure pain sensitivity and impaired descending pain control have
      been associated with chronic pain, but knowledge on the variability in the adult
      general population is lacking. Pressure pain thresholds (PPTs) and descending
      pain control assessed using conditioned pain modulation (CPM) were recorded in a
      randomly selected sample (n = 2,199, 53% female) of the Danish adult general
      population aged 18 to 70 years. PPTs were recorded over the tibialis anterior
      muscle and the upper trapezius muscle. CPM was defined as the difference between
      PPT assessments before and during conditioning with cold pressor pain (hand) for
      2 minutes. Conditioning pain intensity was assessed using a visual analog scale
      and questionnaire data were collected. Female sex (P < .001) and younger age (P
      <= .02) was associated with lower PPTs at both body sites. For the trapezius
      muscle, high perceived stress was associated with lower PPTs (P < .02), whereas
      an interaction was found between body mass index and sex. CPM potency was lower
      in female compared with male participants (P <= .003), whereas no association
      with age was found. Higher level of education (P <= .05), premature withdrawal
      from the cold pressor test (P <= .02), and high visual analog scale score (P <=
      .02) were associated with a larger CPM response. PERSPECTIVE: Data from this
      large population-based study provide new insight into the gender and age
      variation in pain sensitivity and CPM response. Decreased CPM potency and
      increased pain sensitivity in female participants were found, emphasizing the
      need to improve the understanding of its clinical consequences.

PMID- 27884692
TI  - Delta-beta coupling is associated with paternal caregiving behaviors during
      preschool.
AB  - Neural systems that index self-regulation have been associated with mental health
      outcomes, including risk for anxiety problems, from early in life. Yet, little is
      known about the environmental factors that may impact the development of neural
      systems of regulation. Behavioral work suggests that sensitive parenting, or
      parents' ability to correctly interpret and respond to children's signals,
      supports the development of regulation. Conversely, harsh parenting, or
      uninvolved or punitive parent behaviors, is thought to compromise developing
      regulatory systems. We recorded preschoolers' baseline electroencephalography
      (EEG) and tested whether individual differences in delta-beta coupling were
      linked to sensitive or harsh parenting behaviors in mothers and fathers. Using
      Fisher's r-to-z transform, we found that preschoolers whose fathers were low (vs.
      high) in harsh parenting showed greater coupling at parietal electrode sites
      (z=2.66, p=0.00); preschoolers whose fathers were high (vs. low) in harsh
      parenting showed greater coupling at frontal electrode sites (z=-2.14, p=0.02).
      Heightened coupling at frontal electrodes was also visible for children who
      showed high (vs. low) levels of social fear (z=-2.11, p=0.02), suggesting that
      enhanced frontal coupling may be associated with increased risk for anxiety
      problems. No differences in coupling were seen based on levels of sensitive
      parenting behaviors in mothers or fathers. Results provide initial evidence that
      harsh parenting behaviors in fathers are associated with differences in a general
      index of neural regulation in preschoolers, which may have implications for the
      development of social fear in early life.

PMID- 27884693
TI  - Design, synthesis, and characterization of rhein analogs as novel inhibitors of
      scavenger receptor A.
AB  - Scavenger receptor A (SRA) has been known as an immunosuppressive factor and
      therefore therapeutic inhibition of SRA may be potentially exploited for cancer
      immunotherapy. Our previously work suggested that rhein may act as an inhibitor
      of SRA in reversing immunosuppression of SRA during T cells activation. Herein,
      three deconstruction analogs of rhein, compound 1, 2, and 3, were further studied
      as inhibitors of SRA. These three compounds, particularly compound 1, also known
      as a natural product danthron, enhanced T cells activation, indicated by
      increased transcriptional activation of interleukin 2 (Il2) gene, production of
      IL-2 protein, and proliferation of T cells. Additionally, the interaction between
      these compounds and SRA was studied by molecular modeling. Compound 1 showed a
      favorable binding mode with the cysteine rich domain of SRA protein compared to
      compound 2 and 3. Collectively, those results would provide insight for future
      design and development of next generation rhein derivatives as SRA inhibitors.

PMID- 27884691
TI  - AAPT Diagnostic Criteria for Chronic Cancer Pain Conditions.
AB  - : Chronic cancer pain is a serious complication of malignancy or its treatment.
      Currently, no comprehensive, universally accepted cancer pain classification
      system exists. Clarity in classification of common cancer pain syndromes would
      improve clinical assessment and management. Moreover, an evidence-based taxonomy
      would enhance cancer pain research efforts by providing consistent diagnostic
      criteria, ensuring comparability across clinical trials. As part of a
      collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical
      Trial Translations, Innovations, Opportunities, and Networks (ACTTION) and the
      American Pain Society (APS), the ACTTION-APS Pain Taxonomy initiative worked to
      develop the characteristics of an optimal diagnostic system. After the
      establishment of these characteristics, a working group consisting of clinicians
      and clinical and basic scientists with expertise in cancer and cancer-related
      pain was convened to generate core diagnostic criteria for an illustrative sample
      of 3 chronic pain syndromes associated with cancer (ie, bone pain and pancreatic
      cancer pain as models of pain related to a tumor) or its treatment (ie,
      chemotherapy-induced peripheral neuropathy). A systematic review and synthesis
      was conducted to provide evidence for the dimensions that comprise this cancer
      pain taxonomy. Future efforts will subject these diagnostic categories and
      criteria to systematic empirical evaluation of their feasibility, reliability,
      and validity and extension to other cancer-related pain syndromes. PERSPECTIVE:
      The ACTTION-APS chronic cancer pain taxonomy provides an evidence-based
      classification for 3 prevalent syndromes, namely malignant bone pain, pancreatic
      cancer pain, and chemotherapy-induced peripheral neuropathy. This taxonomy
      provides consistent diagnostic criteria, common features, comorbidities,
      consequences, and putative mechanisms for these potentially serious cancer pain
      conditions that can be extended and applied with other cancer-related pain
      syndromes.

PMID- 27884694
TI  - Synthesis and carbonic anhydrase inhibitory properties of novel chalcone
      substituted benzenesulfonamides.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes involved in many
      bioprocesses, through catalysis of the reversible hydration/dehydration process
      of CO2/HCO3-. The inhibition of human CA isoforms I and II with a new series of
      sulfonamide derivatives incorporating substituted chalcone moieties were studied
      in this study. All these newly synthesized sulfonamides demonstrated important
      inhibitory profiles to these CA isoforms with KIs in the range of 9.88 to
      55.43nM, making these compounds interesting leads, with potential applications in
      medicinal chemistry.

PMID- 27884696
TI  - Design, synthesis and antifungal activity of novel fenfuram-diarylamine hybrids.
AB  - Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their
      antifungal activities against four phytopathogenic fungi have been evaluated in
      vitro and most of the compounds demonstrated a significant antifungal activities
      against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited
      the most potent antifungal activity against R. solani with an EC50 value of
      0.037mg/L, far superior to the commercially available fungicide boscalid
      (EC50=1.71mg/L) and lead fungicide fenfuram (EC50=6.18mg/L). Furthermore,
      scanning electron microscopy images showed that the mycelia on treated media grew
      abnormally with tenuous, wizened and overlapping colonies compared to the
      negative control. Molecular docking studies revealed that compound 5e featured a
      higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it
      was shown that the 3-chlorophenyl group in compound 5e formed a CH-pi interaction
      with B/Trp-206 and a Cl-pi interaction with D/Tyr-128, rendering compound 5e more
      active than fenfuram against SDH.

PMID- 27884695
TI  - Linker dependent intercalation of bisbenzimidazole-aminosugars in an RNA duplex;
      selectivity in RNA vs. DNA binding.
AB  - Neomycin and Hoechst 33258 are two well-known nucleic acid binders that interact
      with RNA and DNA duplexes with high affinities respectively. In this manuscript,
      we report that covalent attachment of bisbenzimidazole unit derived from Hoechst
      33258 to neomycin leads to intercalative binding of the bisbenzimidazole unit
      (oriented at 64-74 degrees  with respected to the RNA helical axis) in a linker
      length dependent manner. The dual binding and intercalation of conjugates were
      supported by thermal denaturation, CD, LD and UV-Vis absorption experiments.
      These studies highlight the importance of linker length in dual recognition by
      conjugates, for effective RNA recognition, which can lead to novel ways of
      recognizing RNA structures. Additionally, the ligand library screens also
      identify DNA and RNA selective compounds, with compound 9, containing a long
      linker, showing a 20.3 degrees C change in RNA duplex Tm with only a 13.0 degrees
      C change in Tm for the corresponding DNA duplex. Significantly, the shorter
      linker in compound 3 shows almost the reverse trend, a 23.8 degrees C change in
      DNA Tm, with only a 9.1 degrees C change in Tm for the corresponding RNA duplex.

PMID- 27884698
TI  - Alteration of the brain morphology and the response to the acute stress in the
      recombinant mouse lines with different predisposition to catalepsy.
AB  - Catalepsy is an inability to correct an externally imposed awkward posture; it is
      associated with schizophrenia and depression in human. We created new recombinant
      B6.CBA-D13Mit76C and B6.CBA-D13Mit76B mouse lines on the C57Bl/6 genome, carrying
      the 102.73-110.56Mbp fragment of chromosome 13 derived from the catalepsy-prone
      CBA strain and catalepsy-resistant C57BL/6 strain, respectively. We compared the
      behavior and brain morphology (11.7T BioSpec 117/16 USR tomograph, Germany) in
      these lines. The effects of acute emotional stress on corticosterone's level in
      the blood and mRNA expression of Bdnf and Arc genes in the brain were
      investigated. The B6.CBA-D13Mit76B mice were non-cataleptic, while about 17% of
      B6.CBA-D13Mit76C mice demonstrated catalepsy-like immobility. No difference
      between these lines was revealed in the open field and social interaction tests.
      In the Morris water maze test, both lines effectively found the platform on the
      fourth day; however B6.CBA-D13Mit76B mice achieved significantly better results
      than cataleptic-prone animals. B6.CBA-D13Mit76C mice were characterized by
      decreased volume of the total brain and reduced sizes of striatum, cerebellum and
      pituitary gland. The both lines showed the similar basal and stress-induced
      levels of corticosterone, while the brain expression of Bdnf and Arc genes was
      more vulnerable to stress in the catalepsy-prone B6.CBA-D13Mit76C line.

PMID- 27884697
TI  - 3-Cyano-6-(5-methyl-3-pyrazoloamino) pyridines (Part 2): A dual inhibitor of
      Aurora kinase and tubulin polymerization.
AB  - A new class of a dual inhibitor of Aurora kinase and tubulin polymerization was
      created by introducing various substituted phenoxyethylamino or
      pyridyloxyethylamino groups to the 2-position of 3-cyano-4-methyl-6-(5-methyl-3
      pyrazoloamino)-pyridine. Compound 3g exhibited Aurora kinase inhibition,
      excellent protein kinase selectivity to Aurora kinase in comparison with 66 other
      kinases, inhibition of phosphorylation of Ser10 of histone H3 as an Aurora kinase
      inhibitor, inhibition of tubulin polymerization in vitro, good cell membrane
      permeability, and a good PK profile. Therefore compound 3g was effective in some
      antitumor mouse models at a dose of 30mg/kgpoqd.

PMID- 27884699
TI  - Cell adhesion molecules and sleep.
AB  - Cell adhesion molecules (CAMs) play essential roles in the central nervous
      system, where some families are involved in synaptic development and function.
      These synaptic adhesion molecules (SAMs) are involved in the regulation of
      synaptic plasticity, and the formation of neuronal networks. Recent findings from
      studies examining the consequences of sleep loss suggest that these molecules are
      candidates to act in sleep regulation. This review highlights the experimental
      data that lead to the identification of SAMs as potential sleep regulators, and
      discusses results supporting that specific SAMs are involved in different aspects
      of sleep regulation. Further, some potential mechanisms by which SAMs may act to
      regulate sleep are outlined, and the proposition that these molecules may serve
      as molecular machinery in the two sleep regulatory processes, the circadian and
      homeostatic components, is presented. Together, the data argue that SAMs regulate
      the neuronal plasticity that underlies sleep and wakefulness.

PMID- 27884700
TI  - Claudin-5, -7, and -18 suppress proliferation mediated by inhibition of
      phosphorylation of Akt in human lung squamous cell carcinoma.
AB  - Abnormal expression of claudin (CLDN) subtypes has been reported in various solid
      cancers. However, it is unknown which subtype plays a key role in the regulation
      of proliferation in cancer cells. The expression of CLDN3-5, 7, and 18 in human
      lung squamous carcinoma tissues was lower than that in normal tissue. Here, we
      examined which combination of exogenous CLDNs expression inhibits proliferation
      and the molecular mechanism using human lung squamous RERF-LC-AI cells. Real-time
      polymerase chain reaction and western blotting showed that CLDN3-5, 7, and 18 are
      little expressed in RERF-LC-AI cells. In the exogenously transfected cells,
      CLDN5, 7, and 18 were distributed in the cell-cell contact areas concomitant with
      ZO-1, a tight junctional scaffolding protein, whereas CLDN3 and 4 were not. Cell
      proliferation was individually and additively suppressed by CLDN5, 7, and 18. The
      expression of these CLDNs showed no cytotoxicity compared with mock cells. CLDN5,
      7, and 18 increased p21 and decreased cyclin D1, resulting in the suppression of
      cell cycle G1-S transition. The expression of these CLDNs inhibited
      phosphorylation of Akt without affecting phosphorylated ERK1/2. Furthermore,
      these CLDNs inhibited the nuclear localization of Akt and its association with 3
      phosphoinositide-dependent protein kinase-1 (PDK1). The suppression of G1-S
      transition caused by CLDN5, 7, and 18 was rescued by the expression of
      constitutively active-Akt. We suggest that the reduction of CLDN5, 7, and 18
      expression loses the suppressive ability of interaction between PDK1 and Akt and
      causes sustained phosphorylation of Akt, resulting in the disordered
      proliferation in lung squamous carcinoma cells.

PMID- 27884702
TI  - Assessing the purity of regulatory T cells: A humble reminder.

PMID- 27884701
TI  - Cardiac inositol 1,4,5-trisphosphate receptors.
AB  - Calcium is a second messenger that regulates almost all cellular functions. In
      cardiomyocytes, calcium plays an integral role in many functions including muscle
      contraction, gene expression, and cell death. Inositol 1,4,5-trisphosphate
      receptors (IP3Rs) are a family of calcium channels that are ubiquitously
      expressed in all tissues. In the heart, IP3Rs have been associated with
      regulation of cardiomyocyte function in response to a variety of neurohormonal
      agonists, including those implicated in cardiac disease. Notably, IP3R activity
      is thought to be essential for mediating the hypertrophic response to multiple
      stimuli including endothelin-1 and angiotensin II. In this review, we will
      explore the functional implications of IP3R activity in the heart in health and
      disease.

PMID- 27884704
TI  - Enhanced aggressiveness of bystander cells in an anti-tumor photodynamic therapy
      model: Role of nitric oxide produced by targeted cells.
AB  - The bystander effects of anti-cancer ionizing radiation have been widely studied,
      but far less is known about such effects in the case of non-ionizing photodynamic
      therapy (PDT). In the present study, we tested the hypothesis that
      photodynamically-stressed prostate cancer PC3 cells can elicit nitric oxide (NO)
      mediated pro-growth/migration responses in non-stressed bystander cells. A novel
      approach was used whereby both cell populations existed on a culture dish, but
      made no physical contact with one other. Visible light irradiation of target
      cells sensitized with 5-aminolevulinic acid-induced protoporphyrin IX resulted in
      a striking upregulation of inducible nitric oxide synthase (iNOS) along with NO,
      the level of which increased after irradiation. Slower and less pronounced
      iNOS/NO upregulation was also observed in bystander cells. Activation of
      transcription factor NF-kappaB was implicated in iNOS induction in both targeted
      and bystander cells. Like surviving targeted cells, bystanders exhibited a
      significant increase in growth and migration rate, both responses being strongly
      attenuated by an iNOS inhibitor (1400W), a NO scavenger (cPTIO), or iNOS
      knockdown. Incubating bystander cells with conditioned medium from targeted cells
      failed to stimulate growth/migration, ruling out involvement of relatively long
      lived stimulants. The following post-irradiation changes in pro-survival/pro
      growth proteins were observed in bystander cells: upregulation of COX-2 and
      activation of protein kinases Akt and ERK1/2, NO again playing a key role. This
      is the first reported evidence for NO-enhanced bystander aggressiveness in the
      context of PDT. In the clinical setting, such effects could be averted through
      pharmacologic use of iNOS inhibitors as PDT adjuvants.

PMID- 27884705
TI  - Analytical and clinical validation of the new ultrasensitive Roche Thyroglobulin
      II assay.

PMID- 27884706
TI  - Identification and functional characterization of a novel Spatzle gene in
      Litopenaeus vannamei.
AB  - Shrimp innate immunity is the first line of resistance against pathogenic
      bacteria. The Toll-like receptor (TLR)-NF-kappaB pathway is vital in this
      immunity process. In this study, a novel Spatzle gene (LvSpz4) of Litopenaeus
      vannamei was cloned and functionally characterized. The open reading frame of
      LvSpz4 was 918 bp, which encoded a putative protein with 305 amino acids. LvSpz4
      was most expressed in the gills of L. vannamei. This expression was induced by
      Vibrio alginolyticus or Staphylococcus aureus infection or lipopolysaccharide
      stimulation. The reporter gene assay showed that LvSpz4 could activate the
      promoters of Pen4, Drs, AttA, Mtk, and white spot syndrome virus immediate early
      gene1 in Drosophila Schneider 2 (S2) cells. Knockdown LvSpz4 increased the
      cumulative mortality of L. vannamei upon V. alginolyticus infection. The unfolded
      protein response (UPR) induced the expression of LvSpz4 in L. vannamei. Moreover,
      the promoter of LvSpz4 was activated by L. vannamei X-Box binding protein 1 and
      activating transcription factor 4 in S2 cells. These results suggested that
      LvSpz4 was involved in L. vannamei innate immunity and caused the crosstalk
      between the TLR-NF-kappaB pathway and UPR.

PMID- 27884708
TI  - Strategies for Trypanosoma brucei gambiense elimination.

PMID- 27884707
TI  - Polyclonal anti-Candida antibody improves phagocytosis and overall outcome in
      zebrafish model of disseminated candidiasis.
AB  - Fungal infections are a major cause of animal and plant morbidity and mortality
      worldwide. Effective biological therapeutics could complement current antifungal
      drugs, but understanding of their in vivo mechanisms has been hampered by
      technical barriers to intravital imaging of host-pathogen interactions. Here we
      characterize the fungal infection of zebrafish as a model to understand the
      mechanism-of-action for biological antifungal therapeutics through intravital
      imaging of these transparent animals. We find that non-specific human IgG
      enhances phagocytosis by zebrafish phagocytes in vivo. Polyclonal anti-Candida
      antibodies enhance containment of fungi in vivo and promote survival. Analysis
      suggests that early phagocytic containment is a strong prognostic indicator for
      overall survival. Although polyclonal anti-Candida antibodies protect against
      disease, this is not necessarily the case for individual monoclonal anti-Candida
      antibodies. Thus, the zebrafish appears to provide a useful model host for
      testing if a biological therapeutic promotes phagocytosis in vivo and enhances
      protection against candidemia.

PMID- 27884709
TI  - Seeing beyond 2020: an economic evaluation of contemporary and emerging
      strategies for elimination of Trypanosoma brucei gambiense.
AB  - BACKGROUND: Trypanosoma brucei (T b) gambiense is targeted to reach elimination
      as a public health problem by 2020 and full elimination by 2030. To achieve these
      goals, stakeholders need to consider strategies to accelerate elimination. Hence,
      we aimed to model several options related to current and emerging methods for
      case detection, treatment, and vector control across settings to assess cost
      effectiveness and the probability of elimination. METHODS: Five intervention
      strategies were modelled over 30 years for low, moderate, and high transmission
      settings. Model parameters related to costs, efficacy, and transmission were
      based on available evidence and parameter estimation. Outcomes included
      disability-adjusted life-years (DALYs), costs, and long-term prevalence.
      Sensitivity analyses were done to calculate the uncertainty of the results.
      FINDINGS: To reach elimination targets for 2020 across all settings, approaches
      combining case detection, treatment, and vector control would be most effective.
      Elimination in high and moderate transmission areas was probable and cost
      effective when strategies included vector control and novel methods, with
      incremental cost-effectiveness ratios (ICERs) ranging from US$400 to $1500 per
      DALY averted. In low transmission areas, approaches including the newest
      interventions alone or in combination with tiny targets (vector control) were
      cost-effective, with ICERs of $200 or $1800 per DALY averted, respectively, but
      only strategies including vector control were likely to lead to elimination.
      Results of sensitivity analyses showed that allowing for biennial surveillance,
      reducing vector control maintenance costs, or variations of active surveillance
      coverage could also be cost-effective options for elimination, depending on the
      setting. INTERPRETATION: Although various strategies might lead to elimination of
      T b gambiense, cost-effective approaches will include adoption of emerging
      technologies and, in some settings, increased surveillance or implementation of
      vector control. FUNDING: Bill & Melinda Gates Foundation.

PMID- 27884710
TI  - Predisposing Factors for Re-interventions with Additional Iliac Stent Grafts
      After Endovascular Aortic Repair.
AB  - BACKGROUND: Endoleaks of type Ib and III are relatively common causes of re
      intervention after EVAR. The aim was to determine underlying causes and identify
      anatomical factors associated with these re-interventions. METHODS: A total of
      444 patients with standard bifurcated stent grafts were included in a
      retrospective observational study. Patients requiring additional iliac stent
      grafts (n = 24) were compared to those who did not (n = 420). Pre- and post
      operative CT examinations were reviewed in patients with additional iliac stents.
      Reasons for re-interventions were defined as migration (>5 mm at the distal end
      or at interconnections), progression of disease (iliac artery diameter exceeding
      graft diameter), inadequate distal seal length at primary repair, or a
      combination of these factors. RESULTS: Twenty-four patients received 31
      additional grafts in 30 limbs after a median 46 months (range 2-92 months). Five
      re-interventions (21%) were due to rupture. Re-intervened limbs had a larger
      iliac artery diameter 18 mm (25th and 75th percentile 20-25) versus 15 mm (13-18
      mm), p < .001. The degree of iliac limb oversizing at primary EVAR was lower in
      re-intervened patients (11% (8-18%) versus 18% (12-26%), p = .003). In re
      intervened patients, iliac attachment zones were shorter in treated limbs than in
      untreated 23 mm (11-34) versus 34 mm (25-44), p < .001). Sixteen of 31 re
      interventions (51%) were caused by migration (10 at the distal landing site, 6 at
      interconnections), nine of 31 (29%) by disease progression, and nine of 31 (29%)
      had inadequate initial stent graft placement. Three of 31 re-interventions (10%)
      were done as proactive procedures. CONCLUSIONS: Additional iliac stent grafting
      occurred late after primary repair; a considerable number were caused by rupture.
      A low degree of oversizing, migration at the distal landing site, separation of
      stent graft interconnections, disease progression at the distal landing site, and
      inadequate initial stent graft placement may all contribute. Patients with large
      iliac dimensions and short attachment zones may need a larger degree of
      oversizing and more vigorous surveillance.

PMID- 27884703
TI  - Mechanistic and biological considerations of oxidatively damaged DNA for helicase
      dependent pathways of nucleic acid metabolism.
AB  - Cells are under constant assault from reactive oxygen species that occur
      endogenously or arise from environmental agents. An important consequence of such
      stress is the generation of oxidatively damaged DNA, which is represented by a
      wide range of non-helix distorting and helix-distorting bulkier lesions that
      potentially affect a number of pathways including replication and transcription;
      consequently DNA damage tolerance and repair pathways are elicited to help cells
      cope with the lesions. The cellular consequences and metabolism of oxidatively
      damaged DNA can be quite complex with a number of DNA metabolic proteins and
      pathways involved. Many of the responses to oxidative stress involve a
      specialized class of enzymes known as helicases, the topic of this review.
      Helicases are molecular motors that convert the energy of nucleoside triphosphate
      hydrolysis to unwinding of structured polynucleic acids. Helicases by their very
      nature play fundamentally important roles in DNA metabolism and are implicated in
      processes that suppress chromosomal instability, genetic disease, cancer, and
      aging. We will discuss the roles of helicases in response to nuclear and
      mitochondrial oxidative stress and how this important class of enzymes help cells
      cope with oxidatively generated DNA damage through their functions in the
      replication stress response, DNA repair, and transcriptional regulation.

PMID- 27884711
TI  - Patients with Small Abdominal Aortic Aneurysm are at Significant Risk of
      Cardiovascular Events and this Risk is not Addressed Sufficiently.
AB  - BACKGROUND: Patients with abdominal aortic aneurysm (AAA) are at significant risk
      of cardiovascular (CV) events. Recent implementation of AAA-screening means
      thousands of patients are now diagnosed with small-AAA; however, CV risk factors
      are not always addressed. This study aimed at assessing and quantifying the CV
      characteristics of patients with small AAA following the introduction of
      screening programmes. METHODS: CV profiles of 384 men with a small AAA (<55 mm
      diameter) were assessed through the United Kingdom Aneurysm Growth Study (UKAGS),
      a nationwide prospective cohort study of men with small AAA. A prospective local
      cohort of an additional 142 patients with small AAA with available blood pressure
      (BP) and lipid profiles was also included and followed-up for 1 year. RESULTS: In
      the UKAGS population, 54% were current and 30% ex-smokers; 58% were hypertensive
      and 54% hypercholesterolaemic. In the local group, 54% were current and 40% were
      ex-smokers, and 94% were hypertensive. Patients were not more likely to receive
      CV medication after entering AAA surveillance in either group. All local patients
      were clustered "high-risk" for future CV events based on the Framingham score
      (mean 21.8%, 95% CI 20.0-23.6), JBS-2 (16.3%, 14.7-17.9) and ASSIGN (25.2%, 22.7
      27.7). No change was seen in systolic BP levels between baseline and 1 year
      (140.9 mmHg vs. 142.5 mmHg, p=.435). A rise was seen in cholesterol (4.0 mmol-4.2
      mmol, p<.0001) values at 1 year. CONCLUSIONS: This study suggests that patients
      with small AAA are at significant risk for developing CV events and this is not
      currently addressed, which is evident by the "high-risk" CV risk profiles of
      these patients despite being in AAA surveillance. Design and implementation of a
      CV risk reduction programme tailored for this population is necessary.

PMID- 27884712
TI  - Solid lipid nanoparticles for sustained pulmonary delivery of Yuxingcao essential
      oil: Preparation, characterization and in vivo evaluation.
AB  - The objective of this study was to prepare solid lipid nanoparticles (SLNs) for
      sustained pulmonary delivery of Yuxingcao essential oil (YEO). Three YEO loaded
      SLNs (SLN-200, SLN-400 and SLN-800) with different particle size were prepared
      and separated following a high-shear homogenization technique using Compritol 888
      ATO as lipid and polyvinyl alcohol as an emulsifier. The particle size, zeta
      potential, drug encapsulation efficiency and drug loading of the SLNs were
      determined to be between 171 and 812nm, -17.1 and -19.3mV, between 76.6 and 90.2%
      and between 2.34 and 3.12%, respectively whereas the in vitro release data showed
      that the SLNs led to sustained drug release up to 48h. In addition, the SLN
      suspensions after nebulization conferred the fine particle fractions (<5.4MUm) of
      67.4-75.8%. Following intratracheal administration to rats, YEO loaded SLNs not
      only prolonged pulmonary retention up to 24h, but also increased AUC values
      (15.4, 18.2 and 26.3MUg/gh for SLN-200, SLN-400 and SLN-800, respectively) by 4.5
      7.7 folds compared to the intratracheally dosed YEO solution and by 257-438 folds
      to the intravenously dosed YEO solution, respectively. The present results were
      the first to show that YEO loaded SLNs may sustain YEO inhalation delivery and
      improve local bioavailability, representing a promising inhalable carrier to
      attain once daily application.

PMID- 27884713
TI  - Paclitaxel-loaded polymeric nanoparticles combined with chronomodulated
      chemotherapy on lung cancer: In vitro and in vivo evaluation.
AB  - The objective of our study was to examine the anti-tumor effect of paclitaxel
      (PTX)-loaded polymeric nanoparticles (PTX-NPs) combined with circadian
      chronomodulated chemotherapy. Our intention was to screen out the best time of
      the day for the drug to be administered. PTX-NPs with a diameter of approximately
      168nm were prepared through a thin film dispersion technique. The PTX in PTX-NPs
      showed an initial fast release subsequently a slower and sustained release. The
      cytotoxicity of chronomodulated administration of PTX-NPs in vitro confirmed that
      its cytotoxic effect was lower than that of PTX injection, and showed a time
      dependent effect. In addition, anti-tumor effect was examined by analysing tumor
      growth inhibition rate, micro-vessel density (MVD), cell proliferation and cell
      apoptosis, following either injection with PTX or administration of PTX-NPs.
      Micro fluorine-18-deoxyglucose PET/computed tomography (18F-FDG PET/CT) was used
      to evaluate tumor reactivity to PTX-NPs combined with chronomodulated
      chemotherapy. Taken these results into consideraion, our experiment indicates
      that PTX-NPs exhibit greater anti-tumor activity against A549 cells, in
      comparison with PTX injection, and the anti-tumor effect at 15h after light onset
      (HALO) administration is the best in all groups. Therefore, prepared PTX-NPs
      combined with chronomodulated chemotherapy could be a potential treatment for
      lung cancer.

PMID- 27884714
TI  - Carrier particle design for stabilization and isolation of drug nanoparticles.
AB  - Nanoparticles of poorly water-soluble drugs were prepared in suspension via
      antisolvent precipitation in order to improve their dissolution behaviour.
      Insoluble, surface-functionalized, micron-range, clay carrier particles were
      employed for the dual purpose of stabilizing the nanoparticles in suspended
      state, and facilitating their unhindered isolation to solid state; often a
      challenging step in nanoparticle production. The carrier particles, which were
      functionalized with an optimal level of cationic polymer (protamine), attracted
      negatively-charged nanoparticles to their surface as a uniform and segregated
      nanoparticle layer, at drug loadings up to 9% w/w. By using carrier particles to
      stabilise the nanoparticles on their surface, the traditionally used solubilised
      nanosuspension stabilisers could be eliminated, thus avoiding time-consuming
      stabiliser screening tests. The carrier particle system facilitated stabilisation
      of nanoparticles in suspension, isolation of nanoparticles to the solid state via
      filtration, and preservation of fast nanoparticle-induced dissolution rates of
      the dried nanoparticle-carrier composites, indicating preservation of their high
      surface area during drying. The process was validated with two poorly water
      soluble BCS Class II drugs, fenofibrate and mefenamic acid, both of which
      demonstrated negative surface charge in aqueous suspension.

PMID- 27884715
TI  - Improved sustained release of antigen from immunostimulatory DNA hydrogel by
      electrostatic interaction with chitosan.
AB  - Immunostimulatory DNA hydrogel (sDNA hydrogel) containing unmethylated cytosine
      phosphate-guanine (CpG) sequences has been demonstrated to be a useful antigen
      delivery system, which can effectively induce an antigen-specific immune response
      through stimulation of the innate immune system. However, relatively rapid
      release of antigens from the sDNA hydrogel limits its potential. To enhance the
      potency of the sDNA hydrogel via improvement of its sustained release property,
      we selected chitosan, a biocompatible cationic polymer which electrostatically
      interacts with DNA, and mixed it with the sDNA hydrogel. Compared to unmixed sDNA
      hydrogel, sDNA hydrogel mixed with chitosan (Chitosan-sDNA hydrogel) was more
      stable, tougher, had more bound water, released a model antigen ovalbumin (OVA)
      more slowly in vitro, and provided longer retention of OVA at the injection site
      after intradermal injection into mice. Intradermal immunization of mice with the
      OVA-loaded Chitosan-sDNA hydrogel resulted in the induction of a higher level of
      OVA-specific IgG in serum compared with OVA-loaded sDNA hydrogel with no
      chitosan. These results indicate that the Chitosan-sDNA hydrogel is an improved
      sustained release formulation for efficient induction of antigen-specific immune
      responses.

PMID- 27884716
TI  - Therapeutic effects of traditional Chinese medicine Niubeixiaohe in mouse
      tuberculosis models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine Niubeixiaohe
      (NBXH) is an effective anti-tuberculosis prescription, which is made up of Bulbus
      Fritillariae Cirrhosae, Rhizoma Bletillae, Radix Platycodonis, Fructus Arctii,
      Herba Houttuyniae and Glutinous rice. In this study, NBXH powder (I) and three
      kinds of NBXH extracts (II, III, and IV) were prepared. The water decoction of
      NBXH had been used to treat TB in clinic sixteen years suggested that it was
      effective to treat TB. AIM OF THE STUDY: This study evaluated the effects of
      different processing products of NBXH on mouse TB model in vivo and provide a new
      Chinese medicine for the clinical treatment of TB. MATERIALS AND METHODS: In this
      study, 120 female BALB/c mice infected with Mycobacterium tuberculosis H37Rv,
      were treated with distilled water, M. vaccae vaccine, the low, middle and high
      doses of NBXH I, the low, middle and high doses of NBXH II, the low, middle and
      high doses of NBXH III, the low, middle and high doses of NBXH IV for 12 weeks,
      respectively. RESULTS: The body weights of mice in all NBXH groups were higher
      than that in the water group. The weight indexes of the spleens in M. vaccae
      group, the middle dose of NBXH II group, the low dose of NBXH IV group and in the
      high dose of NBXH IV group were significantly lower than that in the water
      group(P<0.05). Compared with the water group, the spleen colony counts in the low
      dose of NBXH I group, the high dose of NBXH II group, the low dose of NBXH III
      group and the high dose of NBXH IV group reduced by 0.43, 0.46, 0.73, 0.58 logs
      (P<0.05), respectively. But the lung colony counts had no significant difference
      between each group. Pulmonary general pathology and histopathology displayed that
      the lung lesions in treatment groups were improved at certain degree, especially
      in the low dose of NBXH IIIand IV groups, in which their areas of the lesions
      were less than 50%, and the half normal lung structure in half of the mice could
      be observed. CONCLUSION: Powder and three extracts of traditional Chinese
      medicine NBXH all had anti-tuberculosis therapeutic effects on mouse tuberculosis
      model, and this study provided a base for the further development of Chinese
      patent medicine NBXH. Also, this is the first report on comprehensive
      experimental research of NBXH extracts coming from six kinds of traditional
      Chinese medicine.

PMID- 27884717
TI  - Activity based evaluation of a traditional Ayurvedic medicinal plant: Saraca
      asoca (Roxb.) de Wilde flowers as estrogenic agents using ovariectomized rat
      model.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Saraca asoca (Roxb.) de Wilde, Ashok, is a
      popular traditional plant used for gynecological disorders. In India, the juice
      of Ashok flowers is traditionally consumed as a tonic by women in case of uterine
      disorders. But despite the use, its estrogenic potency is not yet evaluated and
      thus lacks the scientific recognition and acclaim. AIM OF THE STUDY: This study
      is designed to investigate the estrogenic potential of standardized ethanolic
      extract of Saraca asoca flowers (SAF) using ovariectomized (OVX) female albino
      Wistar rat model. MATERIALS AND METHODS: Saraca asoca flowers were extracted in
      ethanol using hot maceration technique and the extract was standardized in terms
      of content of four phytoestrogens like quercetin, kaempferol, beta-sitosterol and
      luteolin using HPTLC technique. Safety of the extract was evaluated at a dose of
      2000mg/kg body weight in female albino Wistar rats as per the OECD guidelines.
      Bilateral ovariectomy surgery was performed for the excision of both the ovaries.
      The OVX animals were treated with the ethanolic extract of SAF at three dose
      levels- 100mg/kg, 200mg/kg and 400mg/kg body weight in distilled water as a
      vehicle, orally once a day for two weeks. Estradiol valerate was employed as a
      modern drug for comparative evaluation of the results. Estrogenic potency was
      studied by assaying the activities of serum and plasma marker enzymes and
      hormones viz. G6PDH, LDH, 17beta-estradiol, progesterone along with cholesterol,
      triglycerides and HDL, and vaginal cornification. The uterotrophic effect was
      evaluated by studying the histoarchitecture of the uterus, effect on uterine
      weight and changes in the levels of uterine glycogen content. RESULTS: HPTLC
      revealed the presence of markers like quercetin, kaempferol, beta-sitosterol and
      luteolin from the ethanolic extract of SAF. The content of the four markers was
      found to be 1.543mg/g, 0.924mg/g, 4.481mg/g and 2.349mg/g, respectively. SAF
      extract was found to be safe at an oral dose of 2000mg/kg body weight in rats.
      Among the three doses administered to ovariectomized rats, treatment with high
      dose was found to be more efficacious when compared with ovariectomized rats.
      CONCLUSION: The findings of this study firmly support the estrogenic potency of
      ethanolic extract of SAF which may be by the reason of phytoestrogens.

PMID- 27884719
TI  - Systematic review and meta-analysis of randomised controlled trials on the
      effectiveness of school-based dental screening versus no screening on improving
      oral health in children.
AB  - OBJECTIVES: The current study aimed to evaluate the effectiveness of school-based
      dental screening versus no screening on improving oral health in children aged 3
      18 years by a systematic review and meta-analysis of randomised controlled
      trials. SOURCES AND STUDY SELECTION: Three sets of independent reviewers searched
      MEDLINE, EMBASE, Web of Science and other sources through April 2016 to identify
      published and nonpublished studies without language restrictions and extracted
      data. DATA: Primary outcomes included prevalence and mean number of teeth with
      caries, incidence of dental attendance and harms of screening. Cochrane's
      criteria for risk of bias assessment were used. RESULTS: A total of five cluster
      RCTs (of unclear or high risk of bias), including 28,442 children, were meta
      analysed. For an intracluster correlation coefficient of 0.030, there was no
      statistically significant difference in dental attendance between children who
      received dental screening and those who did not receive dental screening (RR
      1.11, 95% 0.97, 1.27). The Chi-square test for heterogeneity and the Higgin's I2
      value indicated a substantial heterogeneity. Only one study reported the
      prevalence and mean number of deciduous and permanent teeth with dental caries
      and found no significant differences between the screening and no screening
      groups. CONCLUSIONS: There is currently no evidence to support or refute the
      clinical benefits or harms of dental screening. Routine dental screening may not
      increase the dental attendance of school children, but there is a lot of
      uncertainty in this finding because of the quality of evidence. CLINICAL
      SIGNIFICANCE: Evidence from the reviewed trials suggests no clinical benefit from
      school-based screening in improving children's oral health. However, there is a
      lot of uncertainty in this finding because of the quality of evidence. There is a
      need to conduct a well-designed trial with an intensive follow-up arm and cost
      effectiveness analysis. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42016038828
      (PROSPERO database).

PMID- 27884718
TI  - Micro-CT analysis of naturally arrested brown spot enamel lesions.
AB  - OBJECTIVES: The aim of this study was to characterize the mineral density
      parameters through natural enamel brown spot lesions (BSLs) and to visualize and
      map their mineral distribution pattern in comparison to enamel whitespot lesions
      (WSLs). METHODS: Study specimens included seventeen proximal WSLs (ICDAS 1, 2),
      seventeen proximal BSLs and seventeen sound proximal specimens (ICDAS 0)
      collected from The Oral Surgery Department at Sydney Dental Hospital, Sydney,
      Australia. Imaging was undertaken using a high resolution, desktop micro-computed
      tomography system. A calibration equation was used to transform the grey level
      values of the images into true mineral density values. The qualitative analysis
      and the quantification of the lesion parameters including the mineral density and
      the thickness of the enamel lesion surface layer were performed using mineral
      density profiles plotted in FIJI and the visualized mineral maps in MATLAB
      respectively. RESULTS: The maps of brownspot lesions revealed irregular
      demineralization patterns with faint boundaries and outlines. The regular
      triangular shape of proximal lesions was recognizable only in some parts of
      individual BSLs or was completely unrecognizable within the entire lesion.
      Scattered free-form areas of high density enamel were observed within or close to
      the surface of BSLs. A layer of high density enamel with a mineral density close
      to that of sound enamel was observed in all of the BSLs. The mean mineral density
      of the body of BSLs, including the scattered areas of high mineral density, was
      significantly higher than the corresponding values in white-spot lesions. The
      mean thickness of the surface layer in BSLs (79+/-15MUm) was also significantly
      higher than white-spot lesions (51+/-11MUm) (p<0.05). CONCLUSION: This study
      demonstrated that the mineralization parameters such as density and the thickness
      of the surface layer as well as distribution patterns through natural enamel
      brown spot lesions (BSLs) are different from enamel white-spot lesions (WSLs).
      The higher mineral density of the body of the lesion and the increased thickness
      of the surface layer in brown spot enamel lesions may suggest possible subsurface
      remineralization in the majority of naturally arrested BSLs.

PMID- 27884720
TI  - Penetration of sub-micron particles into dentinal tubules using ultrasonic
      cavitation.
AB  - OBJECTIVES: Functionalised silica sub-micron particles are being investigated as
      a method of delivering antimicrobials and remineralisation agents into dentinal
      tubules. However, their methods of application are not optimised, resulting in
      shallow penetration and aggregation. The aim of this study is to investigate the
      impact of cavitation occurring around ultrasonic scalers for enhancing particle
      penetration into dentinal tubules. METHODS: Dentine slices were prepared from
      premolar teeth. Silica sub-micron particles were prepared in water or acetone.
      Cavitation from an ultrasonic scaler (Satelec P5 Newtron, Acteon, France) was
      applied to dentine slices immersed inside the sub-micron particle solutions.
      Samples were imaged with scanning electron microscopy (SEM) to assess tubule
      occlusion and particle penetration. RESULTS: Qualitative observations of SEM
      images showed some tubule occlusion. The particles could penetrate inside the
      tubules up to 60MUm when there was no cavitation and up to ~180MUm when there was
      cavitation. CONCLUSIONS: The cavitation bubbles produced from an ultrasonic
      scaler may be used to deliver sub-micron particles into dentine. This method has
      the potential to deliver such particles deeper into the dentinal tubules.
      CLINICAL SIGNIFICANCE: Cavitation from a clinical ultrasonic scaler may enhance
      penetration of sub-micron particles into dentinal tubules. This can aid in the
      development of novel methods for delivering therapeutic clinical materials for
      hypersensitivity relief and treatment of dentinal caries.

PMID- 27884721
TI  - Comparison of xenobiotic-metabolising human, porcine, rodent, and piscine
      cytochrome P450.
AB  - Cytochrome P450 proteins (CYP450s) are present in most domains of life and play a
      critical role in the metabolism of endogenous compounds and xenobiotics. The
      effects of exposure to xenobiotics depend heavily on the expression and activity
      of drug-metabolizing CYP450s, which is determined by species, genetic background,
      age, gender, diet, and exposure to environmental pollutants. Numerous reports
      have investigated the role of different vertebrate CYP450s in xenobiotic
      metabolism. Model organisms provide powerful experimental tools to investigate
      Phase I metabolism. The aim of the present review is to compare the existing data
      on human CYP450 proteins (1-3 families) with those found in pigs, mice, and fish.
      We will highlight differences and similarities and identify research gaps which
      need to be addressed in order to use these species as models that mimic human
      traits. Moreover, we will discuss the roles of nuclear receptors in the cellular
      regulation of CYP450 expression in select organisms.

PMID- 27884723
TI  - IR and IGF-1R expression affects insulin induced proliferation and DNA damage.
AB  - Diabetes mellitus type 2 is in its prediagnostic and early phase characterized by
      hyperinsulinemia. Previously, we pointed out hyperinsulinemia as a potential link
      between diabetes mellitus and the increased cancer risk that is associated with
      this disease through its induction of oxidative stress and DNA damage. In the
      present study, we address the relationship between the induction of proliferation
      and genomic damage in vitro in cell lines with different expression of the
      insulin and the IGF-1 receptors after treating the cells with insulin and the
      insulin analog glargine. Contribution of the IGF-1 receptor was further examined
      by application of the IGF-1R inhibitor ((5R,5aS,8aR,9R)-9-hydroxy-5,8,8a,9
      tetrahydro-5-(3,4,5-trimethoxyphenyl)-furo[3_,4_:6,7]-naphtho[2,3-d]-1,3-dioxol
      6(5aH)-one) (PPP). Insulin as well as insulin glargine stimulated cell
      proliferation in IGF-receptor-dominated MCF-7 cells and not in insulin receptor
      dominated BT-474 cells and PPP attenuated this effect. Both insulins induced DNA
      damage which was reduced by PPP in MCF-7 cells only. Overall, we showed in this
      study that high levels of insulin and insulin glargine can enhance cell
      proliferation in cells which highly express IGF-1 receptor and induce DNA damage
      in cells with high and also in those with low IGF-1 receptor levels.

PMID- 27884722
TI  - The Impact of Age on Quality of Life in Breast Cancer Patients Receiving Adjuvant
      Chemotherapy: A Comparative Analysis From the Prospective Multicenter Randomized
      ADEBAR trial.
AB  - BACKGROUND: Elderly breast cancer patients are affected by poorer quality of life
      (QoL) compared to younger patients. Because QoL has a relevant impact on
      guideline-adherent treatment, elderly breast cancer patients are often
      undertreated, especially with regard to adjuvant chemotherapy, and overall
      survival is decreased. Thus, understanding the impact of chemotherapy on QoL in
      elderly patients is crucial. This study compared QoL in patients aged < 65 years
      and 65 to 70 years receiving adjuvant chemotherapy as a secondary outcome in the
      prospective randomized multicenter ADEBAR trial. PATIENTS AND METHODS: Patients
      with lymph node-positive breast cancer were prospectively randomized for either
      sequential anthracycline-taxane or epirubicin/fluorouracil/cyclophosphamid
      chemotherapy (FEC) therapy. QoL was assessed at baseline (t1), before cycle 4
      FEC, and cycle 5 epirubicin/cyclophosphamid-docetaxel (EC-DOC) (t2), 4 weeks
      after chemotherapy (t3), and 6 weeks after radiation (t4) using the European
      Organization for Research and Treatment for Cancer (EORTC) Quality of Life Core
      Questionnaire (QLQ-C30) and the Breast Cancer-Specific Module (QLQ-BR23). We
      compared patients aged < 65 years and 65 to 70 years with respect to QoL and
      discontinuation of chemotherapy. RESULTS: A total of 1363 patients were enrolled
      onto the ADEBAR trial, with 16.7% of the patients aged 65 to 70 years. In elderly
      patients, Eastern Cooperative Oncology Group performance status was higher and
      global health status and physical functioning were lower at baseline. Global
      health status decreased between t1 and t3 by 7 points in patients < 65 years and
      by 11 points in patients 65 to 70 years, and physical functioning decreased in
      the same period by 13.4 points in patients aged < 65 years and by 15.9 points in
      patients 65 to 70 years. In both groups, at t4 global health status exceeded
      baseline by 6 points, and physical functioning was 1.3 points under baseline in
      patients < 65 years old and 3 points under baseline in patients 65 to 70 years.
      There was a trend to more fatigue in elderly patients and to more nausea and
      vomiting while receiving chemotherapy in younger patients at t3. There was a
      higher dropout rate in patients aged 65 to 70 years (25.7%) than in patients aged
      < 65 years (16.2%). CONCLUSION: There were only small or trivial differences in
      QoL in patients aged < 65 years versus 65 to 70 years who were receiving adjuvant
      chemotherapy, although the dropout rate from chemotherapy was notably higher in
      elderly breast cancer patients.

PMID- 27884725
TI  - Endocannabinoid system in sexual motivational processes: Is it a novel
      therapeutic horizon?
AB  - The endocannabinoid system (ECS), which is composed of the cannabinoid receptors
      types 1 and 2 (CB1 and CB2) for marijuana's psychoactive ingredient Delta9
      tetrahydrocannabinol (Delta9-THC), the endogenous ligands (AEA and 2-AG) and the
      enzymatic systems involved in their biosynthesis and degradation, recently
      emerged as important modulator of emotional and non-emotional behaviors. For
      centuries, in addition to its recreational actions, several contradictory claims
      regarding the effects of Cannabis use in sexual functioning and behavior (e.g.
      aphrodisiac vs anti-aphrodisiac) of both sexes have been accumulated. The
      identification of Delta9-THC and later on, the discovery of the ECS have opened a
      potential therapeutic target for sexual dysfunctions, given the partial efficacy
      of current pharmacological treatment. In agreement with the bidirectional
      modulation induced by cannabinoids on several behavioral responses, the
      endogenous cannabinoid AEA elicited biphasic effects on sexual behavior as well.
      The present article reviews current available knowledge on herbal, synthetic and
      endogenous cannabinoids with respect to the modulation of several aspects of
      sexuality in preclinical and human studies, highlighting their therapeutic
      potential.

PMID- 27884724
TI  - Optogenetic stimulation of glutamatergic neuronal activity in the striatum
      enhances neurogenesis in the subventricular zone of normal and stroke mice.
AB  - Neurogenesis in the subventricular zone (SVZ) of the adult brain may contribute
      to tissue repair after brain injuries. Whether SVZ neurogenesis can be
      upregulated by specific neuronal activity in vivo and promote functional recovery
      after stroke is largely unknown. Using the spatial and cell type specific
      optogenetic technique combined with multiple approaches of in vitro, ex vivo and
      in vivo examinations, we tested the hypothesis that glutamatergic activation in
      the striatum could upregulate SVZ neurogenesis in the normal and ischemic brain.
      In transgenic mice expressing the light-gated channelrhodopsin-2 (ChR2) channel
      in glutamatergic neurons, optogenetic stimulation of the glutamatergic activity
      in the striatum triggered glutamate release into SVZ region, evoked membrane
      currents, Ca2+ influx and increased proliferation of SVZ neuroblasts, mediated by
      AMPA receptor activation. In ChR2 transgenic mice subjected to focal ischemic
      stroke, optogenetic stimuli to the striatum started 5days after stroke for 8days
      not only promoted cell proliferation but also the migration of SVZ neuroblasts
      into the peri-infarct cortex with increased neuronal differentiation and improved
      long-term functional recovery. These data provide the first morphological and
      functional evidence showing a unique striatum-SVZ neuronal regulation via a semi
      phasic synaptic mechanism that can boost neurogenic cascades and stroke recovery.
      The benefits from stimulating endogenous glutamatergic activity suggest a novel
      regenerative strategy after ischemic stroke and other brain injuries.

PMID- 27884726
TI  - Deacetylase inhibitors as a novel modality in the treatment of multiple myeloma.
AB  - Deacetylase enzymes remove acetyl groups from histone and nonhistone proteins.
      Dysregulation of deacetylase activity is a hallmark of malignancy, including
      multiple myeloma (MM). Deacetylase inhibitors (DACi) cause epigenetic
      modification and inhibition of the aggresome pathway, resulting in death of MM
      cells. Panobinostat, a pan-DACi, has shown significant clinical benefit and is
      the first DACi approved for the treatment of MM. It is approved for use in
      combination with bortezomib and dexamethasone for the treatment of patients with
      relapsed or relapsed and refractory MM who have received >=2 prior regimens
      including bortezomib and an immunomodulatory drug. Ricolinostat and ACY-241,
      which selectively inhibit HDAC6 and the aggresome pathway, are currently being
      studied in combination with dexamethasone and bortezomib or an immunomodulatory
      drug for the treatment of relapsed and refractory MM. In this review, we discuss
      the data from key clinical trials investigating deacetylase inhibitors as novel
      treatment options for MM.

PMID- 27884727
TI  - Impact of 17beta-estradiol and progesterone on inflammatory and apoptotic
      microRNA expression after ischemia in a rat model.
AB  - 17beta-estradiol (E2) and progesterone (P) are neuroprotective factors in the
      brain preventing neuronal death under different injury paradigms. In previous
      studies, we demonstrated that both steroids dampen neuronal damage, improve local
      energy metabolism and attenuate pro-inflammatory responses. MicroRNAs (miRNAs)
      are small regulators of distinct target genes on the RNA level. Their expression
      patterns are misbalanced in several neurological disorders. To explore the
      regulatory mechanisms of steroid hormones on selected miRNAs and their validated
      targets in ischemia, we used the transient middle cerebral artery occlusion
      (tMCAO) model. 12-week old male rats were subjected to 2h tMCAO and expression
      patterns of miR-223, miR-200c, miR-375, miR-199 and miR-214 (all -3p) were
      determined. Using semi-quantitative real time PCR, we examined the role of E2 or
      P as regulatory factors for miRNAs and theirs target genes. Besides miR-375, all
      mentioned miRNAs showed a steady increase with a peak at 72h post tMCAO, whereas
      highest levels of miR-375 were detected at 12h post tMCAO. E2 or P selectively
      dampened miR-223 and miR-214 but further boosted miR-375 levels. With respect to
      the miR-223 regulated target genes NR2B and GRIA2 which both decreased after
      tMCAO, E2 and P application reversed this effect. Further, steroid treatment
      inhibited the hypoxia-induced increase of the miR-375 target genes Bcl-2 and
      RAD1. These findings provide new insights into the regulatory role of
      neuroprotection mediated by sex steroids in the brain. Both hormones are capable
      of influencing the expression of miRNAs which are relevant during
      neuropathological processes. Thereby, E2 and P indirectly control pro-apoptotic
      and -inflammatory gene translation and provide a mechanism to dampen explosive
      tissue damage.

PMID- 27884728
TI  - Magnetic Resonance Thermometry-Guided Laser Interstitial Thermal Therapy in
      Neurosurgery, a Promising Tool for Dural-Based Lesions?

PMID- 27884729
TI  - Rationale and design of the coronary artery calcium consortium: A multicenter
      cohort study.
AB  - BACKGROUND: Although coronary artery calcium (CAC) has been investigated for over
      two decades, there is very limited data on the association of CAC with cause of
      death. The CAC Consortium is a large ongoing multi-center observational cohort of
      individuals who underwent non-contrast cardiac-gated CAC testing and systematic,
      prospective, long-term follow-up for mortality with ascertainment of cause of
      death. METHODS: Four participating institutions from three states within the US
      (California, Minnesota, and Ohio) have contributed individual-level patient data
      to the CAC Consortium (spanning years 1991-2010). All CAC scans were clinically
      indicated and physician-referred in patients without a known history of coronary
      heart disease. Using strict inclusion and exclusion criteria to minimize missing
      data and to eliminate non-dedicated CAC scans (i.e. concomitant CT angiography),
      a sharply defined and well-characterized cohort of 66,636 patients was assembled.
      Mortality status was ascertained using the Social Security Administration Death
      Master File and a validated algorithm. In addition, death certificates were
      obtained from the National Death Index and categorized using ICD (International
      Classification of Diseases) codes into common causes of death. RESULTS: Mean
      patient age was 54 +/- 11 years and the majority were male (67%). Prevalence of
      CVD risk factors was similar across sites and 55% had a <5% estimated 10-year
      atherosclerotic cardiovascular disease (ASCVD) risk. Approximately 45% had a
      Calcium score of 0 and 11% had an Agatston Score >=400. Over a mean follow-up of
      12 +/- 4 years, there were 3158 deaths (4.15 per 1000 person-years). The majority
      of deaths were due to cancer (37%) and CVD (32%). Most CVD deaths were due to CHD
      (54%) followed by stroke (17%). In general, CAC score distributions were similar
      across sites, and there were similar cause of death patterns. CONCLUSIONS: The
      CAC Consortium is large and highly generalizable data set that is uniquely
      positioned to expand the understanding of CAC as a predictor of mortality risk
      across the spectrum of disease states, allowing innovative modeling of the
      competing risks of cardiovascular and non-cardiovascular death.

PMID- 27884731
TI  - Time-lapse microscopy patent upheld in Europe.
AB  - A case for revoking Stanford University's European patent 2430454 on time-lapse
      microscopy was set out in Reproductive BioMedicine Online by Sterckx et al. in
      2014, on the grounds that the patent claimed a method of diagnosis that was
      excluded under a provision of the European Patent Convention. An opposition at
      the European Patent Office in which this ground was raised has recently concluded
      with a decision that the patent is not excluded from patentability under European
      patent law and is to be upheld. An appeal from this decision has been filed, but
      the possibility of the decision being overturned is, in this author's opinion,
      very limited.

PMID- 27884730
TI  - A Qualitative Application of Diffusion of Innovations to Adolescents' Perceptions
      of Long-Acting Reversible Contraception's Attributes.
AB  - STUDY OBJECTIVE: Long-acting reversible contraceptive (LARC) methods are the most
      effective forms of reversible contraception but adolescents often opt for other,
      less effective methods. In this study we explored how adolescents viewed LARC as
      an innovation to be adopted or rejected, and how their assessment of innovation
      attributes affected their decisions about LARC. DESIGN, SETTING, PARTICIPANTS,
      INTERVENTIONS, AND MAIN OUTCOME MEASURES: Sexually active adolescents between 15
      and 22 years old (n = 22) participated in semistructured qualitative interviews.
      The data underwent a content analysis informed by constructs of the diffusion of
      innovations and emergent interview themes. RESULTS: Data analysis indicated 3
      subgroups of participants on the basis of their inclination to use LARC and the
      mutability of that position: positive/persuaded (n = 7), negative/low knowledge
      (n = 10), and negative/adamant (n = 5). Participants' perceptions of the relative
      advantage, compatibility, complexity, trialability, and observability of LARC
      cohered around subgroup membership. Perceived complexity entailed in obtaining
      LARC and fears about LARC were observed across all participants. All participants
      believed that one has to try LARC to know how it will work for her, personally.
      This led the positive/persuaded group to be undeterred by others' negative
      experiences with LARC and the negative/low knowledge and negative/adamant groups
      to decide LARC was too risky to try. CONCLUSION: Adolescents engage in nuanced
      evaluations of LARC, weighing competing information about LARC while receiving
      anecdotal and empirical information about LARC from various valid sources. To
      reduce the uncertainty about LARC that prohibits trying these methods,
      adolescents require straightforward information about LARC that directly
      addresses the advantages of LARC over other methods coupled with candid
      acknowledgement of the potential disadvantages of LARC.

PMID- 27884732
TI  - Natural killer cell subsets and receptor expression in peripheral blood
      mononuclear cells of a healthy Korean population: Reference range, influence of
      age and sex, and correlation between NK cell receptors and cytotoxicity.
AB  - BACKGROUND: The purpose of this study was to identify CD56bright and CD56dim
      natural killer (NK) cell subsets and analyze their receptors expression in a
      healthy Korean population, and to determine whether receptor expression
      correlates with age, sex, and cytotoxicity. MATERIALS AND METHODS: We performed
      multicolor flow cytometry assays to analyze the expression of various NK cell
      receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and
      NKp46) on both CD3-/CD56dim and CD3-/CD56bright NK cells in whole-blood samples
      from 122 healthy donors. The expression of these receptors was compared according
      to age (<30years, n=22, 30-60years, n=73 and >60years, n=27) and gender (male,
      n=61, female, n=61). NK cell cytotoxicity assays were performed with peripheral
      blood mononuclear cells (PBMCs) from 18 individuals. The results were compared to
      the expression levels of NKp30 and NKp46 receptors. RESULTS: A normal reference
      range for NK cell receptor expression in two NK cell subsets was established.
      NKp46 and NKG2D expression gradually decreased with age (p<0.01 and p<0.05,
      respectively) whereas NK cell proportion and numbers, frequencies of CD56dim
      cells, and CD57 expression increased with age (p<0.01 in all cases). Men showed
      greater NK cell proportion and numbers, frequencies of CD56dim cells, and CD57
      expression compared to those of women (p<0.05 and p<0.001; p<0.01 and p<0.01,
      respectively). Notably, the expression of NKp46 was negatively correlated with NK
      cell frequency (r=-0.42, p<0.001). Furthermore, NK cell cytotoxicity was found to
      positively correlate with NCR expression (p=0.02), but not NK cell proportion
      (p=0.80). CONCLUSION: We have established a profile of NK cell surface receptors
      for a Korean population, and revealed that age and gender have an effect on the
      expression of NK cell receptors in the population. Our data might explain why
      neither NK cell numbers nor proportions correlate with NK cell cytotoxicity.

PMID- 27884734
TI  - Nitric oxide-coupled signaling in odor elicited molecular events in the olfactory
      center of the terrestrial snail, Helix pomatia.
AB  - Olfaction, a chemosensory modality, plays a pivotal role in the orientation and
      behavior of invertebrates. The central olfactory processing unit in terrestrial
      stylomatophoran snails is the procerebrum, which contains NO synthesizing
      interneurons, whose oscillatory currents are believed to be the base of odor
      evoked memory formation. Nevertheless, in this model the up- and downstream
      events of molecular cascades that trigger and follow NO release, respectively,
      have not been studied. Immunocytochemistry and flow cytometry studies performed
      on procerebral neural perikarya isolated from the snail Helix pomatia revealed
      cell populations with discrete DAF-2 fluorescence, indicating the release of
      different amounts of NO. Glutamate increased the intensity of DAF-2 fluorescence,
      and the number of DAF-2 positive non-bursting interneurons, through a mechanism
      likely to involve an NMDA-like receptor. Similarly to glutamate, NO activation
      induced an increase in intracellular cGMP levels through activation of soluble
      guanylyl cyclase. Immunohistochemical localization of proteins possessing the
      phosphorylated target sequence of AGC family kinases (RXXS/T-P), among them
      protein kinase A (RRXS/T-P), showed striking similarities to the distribution of
      NOS/cGMP. Activators of cyclic nucleotide synthesis increased the AGC-kinase
      dependent phosphorylation of discrete proteins with 28, 45, and 55kDamw.
      Importantly, exposure of snails to an attractive odorant induced
      hyperphosphorylation of the 28kDa protein, and increased levels of cGMP
      synthesis. Protein S-nitrosylation and intercellular activation of protein kinase
      G were also suggested as alternative components of NO signaling in the snail
      procerebrum. The present results from Helix pomatia indicate an important role
      for procerebrum NO/cGMP/PKA signaling pathways in the regulation of olfactory
      (food-finding) behavior.

PMID- 27884733
TI  - Hospital-related cost of sepsis: A systematic review.
AB  - OBJECTIVES: This article systematically reviews research on the costs of sepsis
      and, as a secondary aim, evaluates the quality of economic evaluations reported
      in peer-reviewed journals. METHODS: We systematically searched the MEDLINE,
      National Health Service (Abstracts of Reviews of Effects, Economic Evaluation and
      Health Technology Assessment), Cost-effectiveness Analysis Registry and Web of
      Knowledge databases for studies published between January 2005 and June 2015. We
      selected original articles that provided cost and cost-effectiveness analyses,
      defined sepsis and described their cost calculation method. Only studies that
      considered index admissions and re-admissions in the first 30 days were published
      in peer-reviewed journals and used standard treatments were considered. All costs
      were adjusted to 2014 US dollars. Medians and interquartile ranges (IQRs) for
      various costs of sepsis were calculated. The quality of economic studies was
      assessed using the Drummond 10-item checklist. RESULTS: Overall, 37 studies met
      our eligibility criteria. The median of the mean hospital-wide cost of sepsis per
      patient was $32,421 (IQR $20,745-$40,835), and the median of the mean ICU cost of
      sepsis per patient was $27,461 (IQR $16,007-$31,251). Overall, the quality of
      economic studies was low. CONCLUSIONS: Estimates of the hospital-related costs of
      sepsis varied considerably across the included studies depending on the method
      used for cost calculation, the type of sepsis and the population that was
      examined. A standard model for conducting cost improve the quality of studies on
      the costs of sepsis.

PMID- 27884735
TI  - Elderly listeners with low intelligibility scores under reverberation show
      degraded subcortical representation of reverberant speech.
AB  - In order to elucidate why many elderly listeners have difficulty understanding
      speech under reverberation, we investigated the relationship between word
      intelligibility and auditory brainstem responses (ABRs) in 28 elderly listeners.
      We hypothesized that the elderly listeners with low word intelligibility scores
      under reverberation would show degraded subcortical encoding information of
      reverberant speech as expressed in their ABRs towards a reverberant /da/
      syllable. The participants were divided into two groups (top and bottom
      performance groups) according to their word intelligibility scores for anechoic
      and reverberant words, and ABR characteristics between groups were compared. We
      found that correlation coefficients between responses to anechoic and reverberant
      /da/ were lower in the bottom performance group than in the top performance
      group. This result suggests that degraded neural representation toward
      information of reverberant speech may account for lower intelligibility of
      reverberant speech in elderly listeners.

PMID- 27884736
TI  - Brain and intestinal expression of galanin-like peptide (GALP), galanin receptor
      R1 and galanin receptor R2, and GALP regulation of food intake in goldfish
      (Carassius auratus).
AB  - Galanin-like peptide (GALP) is a 60 amino acid neuropeptide originally discovered
      from porcine hypothalamus, and is involved in the regulation of food intake in
      mammals. Since its discovery, GALP and its receptors (GALR1 and GALR2) have been
      characterized in mammals, but no publications are available on GALP in fish and
      other non-mammals. The present study aimed to characterize brain and intestinal
      GALP and its receptors using immunohistochemistry in a teleost, the goldfish
      (Carassius auratus), and to study its effects on feeding behavior. Immunostaining
      of brain sections shows the presence of GALP- and GALR1- and GALR2-like
      immunoreactive cells in different encephalic areas, including the telencephalon,
      some hypothalamic nuclei, the optic tectum, the torus longitudinalis and the
      cerebellum. Signal for GALP was also observed in the fasciculus retroflexus. In
      the gut, GALP-and GALR1 and GALR2 immunoreactive cells were detected in the
      mucosa. Results from the feeding study demonstrate that intracerebroventricular
      administration of GALP (1ng/g bodyweight) increases goldfish food intake at 1h
      post-injection. These observations form the first report on the presence of GALP
      in the fish brain and gut, and also on its modulatory role on fish feeding
      behavior. GALP, as in mammals, appears to be a functional neuropeptide in
      goldfish.

PMID- 27884737
TI  - Botulinum neurotoxin type A alleviates mechanical hypersensitivity associated
      with infraorbital nerve constriction injury in rats.
AB  - We investigated the effect of botulinum neurotoxin type A (BoNT-A) on mechanical
      allodynia and hyperalgesia associated with infraorbital nerve constriction (ION
      CCI) in rats. ION-CCI rats received a subcutaneous BoNT-A injection into the
      whisker pad area on day 7 postoperatively and underwent pain assessment on days
      14 and 21 postoperatively. Rats were assigned to one of four treatment groups
      (n=5 each): ION-CCI+BoNT-A 20pg (low-dose group), ION-CCI+BoNT-A 200pg (high-dose
      group), ION-CCI+saline, and Sham. Mechanical allodynia and hyperalgesia were
      evaluated preoperatively (baseline) and on days 7, 14, and 21 postoperatively.
      After noxious mechanical stimulation of whisker pad skin, the number and
      distribution pattern of the phosphorylated extracellular signal-regulated kinase
      (pERK)-immunoreactive (IR) neurons were analyzed in the trigeminal spinal
      subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2). On day 21,
      nocifensive behavior was attenuated by high-dose but not low-dose BoNT-A
      administration. In addition, after noxious mechanical stimulation of whisker pad
      skin, the numbers of pERK-IR cells in the superficial laminae of Vc and C1-C2
      were significantly lower in the high-dose BoNT-A group than in the ION-CCI+saline
      group. The present findings suggest that, by suppressing Vc neuronal activity,
      high-dose intradermal injection of BoNT-A at the site of ION innervation
      alleviates mechanical facial allodynia and hyperalgesia associated with ION-CCI.

PMID- 27884738
TI  - Development of the human oculomotor nuclear complex: Centrally-projecting Edinger
      Westphal nucleus.
AB  - BACKGROUND: The cytoarchitecturally defined Edinger-Westphal nucleus (EW) is now
      referred to by many investigators as the centrally-projecting EW (EWcp) in
      humans. Although the mature structure is well-characterized, there have been few
      reports describing the precise morphology of this nucleus during the second half
      of gestation. SUBJECTS/DESIGN: Eleven brains were examined from preterm infants,
      aged 20-39 postmenstrual weeks, who died of various causes. After fixation, the
      brains were embedded in celloidin and serial sections of 30-MUm thickness were
      cut in the horizontal plane. Sections were stained using the Kluver-Barrera
      method. In addition to microscopic observations, computerized 3D reconstruction
      and morphometry were performed. RESULTS: From 21 weeks, the EWcp had a
      distinctive, complex 3D structure comprising two or three parts. The dorsal part
      was arcuate, half encircling the oculomotor somatic nuclei (OSN). The rostral
      part was the most voluminous, ventral to the rostral OSN, extending anteriorly.
      The caudal part was the smallest, and was composed of several neuronal groups
      near the ventral tip of the OSN. In three cases, the caudal part was absent. It
      could also be joined to the rostral part, forming a ventral part. The total
      volume of the EWcp increased exponentially with age, and the ventral part grew
      more rapidly than the dorsal part. The mean neuronal profile area increased
      linearly with age, and the rate of increase was almost equal between the dorsal
      and ventral parts. CONCLUSIONS: This study suggests that a distinctive, complex,
      two- or three-part 3D structure of the EWcp is preserved after mid-gestation, and
      that the ventral part of the EWcp may expand in volume more rapidly than the
      dorsal part.

PMID- 27884740
TI  - Effect of mechanical debridement with adjunct antimicrobial photodynamic therapy
      in the treatment of peri-implant diseases in type-2 diabetic smokers and non
      smokers.
AB  - OBJECTIVE: The aim of the present 6-month follow-up study was to assess the
      effect of mechanical debridement (MD) with adjunct antimicrobial photodynamic
      therapy (aPDT) in the treatment of peri-implant diseases in type-2 diabetic
      smokers and non-smokers. METHODS: Patients were divided into 2 groups: (a) Group
      1: type-2 diabetic smokers; and (b) Group-2: type-2 diabetic non-smokers. In both
      groups, hemoglobin A1c (HbA1c) levels and peri-implant bleeding on probing (BOP)
      and probing depth (PD) >=4mm were measured at baseline and after 6 months of
      follow-up. Group comparisons were performed using the Kruskall-Wallis test and
      for multiple comparisons Bonferroni post hoc test was used. Level of significance
      was set at P<0.05. RESULTS: Sixty-four individuals (33 in Group-1 and 31 in Group
      2) were included. At baseline, BOP and PD>=4mm were comparable among individuals
      in groups 1 and 2. The mean age of individuals in groups 1 and 2 were 52.6+/-0.8
      and 54.4+/-1.2years, respectively. The mean duration of type-2 DM among patients
      in groups 1 and 2 was 8.2+/-0.3years and 10+/-0.2years, respectively. In Group-1,
      the participants were smoking 6.3+/-1.5 cigarettes daily since 12.7+/-3.3years.
      At 6-months follow-up, there was no statistically significant difference in BOP
      and PD>=4mm among patients in groups 1 and 2 compared with the respective
      baseline values. HbA1c levels were comparable in all groups at all time intervals
      CONCLUSION: Outcomes of the treatment of periimplant diseases using MD with
      adjunct aPDT are comparable among type-2 diabetic smokers and non-smokers.

PMID- 27884739
TI  - Structural and functional improvements due to robot-assisted gait training in the
      stroke-injured brain.
AB  - Robot-assisted gait training (RAGT) can improve walking ability after stroke.
      Because the underlying mechanisms are still unknown, we analyzed changes in post
      stroke injured brains after RAGT. Ten non-ambulatory patients receiving inpatient
      rehabilitation were examined within 3 months of stroke onset. RAGT consisted of
      45min of training, 3days per week. We acquired diffusion tensor imaging (DTI)
      data before and after 20 sessions of RAGT. Fractional anisotropy (FA) maps were
      then used to determine neural changes after RAGT. Fugl-Meyer motor assessment of
      the lower extremity, motricity index of the lower extremity, functional
      ambulation category, and trunk control tests were also conducted before training,
      after 10 and 20 RAGT sessions, and at the 1-month follow-up. After RAGT, the
      supplementary motor area of the unaffected hemisphere showed increased FA, but
      the internal capsule, substantia nigra, and pedunculopontine nucleus of the
      affected hemisphere showed decreased FA. All clinical outcome measures improved
      after 20 sessions of RAGT. Our findings indicate that RAGT can facilitate
      plasticity in the intact supplementary motor area, but not the injured motor
      related areas, in the affected hemisphere.

PMID- 27884741
TI  - Klebsiella and Klebs the person behind the name.

PMID- 27884742
TI  - Antifungals.
AB  - The need for new antifungal agents is undeniable. Current therapeutic choices for
      the treatment of invasive fungal infections are limited to three classes of
      drugs. Most used antifungal agents are not completely effective due to the
      development of resistance, host toxicity and undesirable side effects that limit
      their use in medical practice. Invasive fungal infections have significantly
      increased over the last decades and the mortality rates remain unacceptably high.
      More threatening, new resistance patterns have been observed including
      simultaneous resistance to different antifungal classes. In the last years,
      deeper insights into the molecular mechanisms for fungal resistance and virulence
      have yielded some new potential targets for antifungal therapeutics. Chemical
      genomics-based screenings, high throughput screenings of natural products and
      repurposing of approved drugs are some of the approaches being followed for the
      discovery of new antifungal molecules. However, despite the emerging need for
      effective antifungal agents, the current pipeline contains only a few promising
      molecules, with novel modes of action, in early clinical development stages.

PMID- 27884743
TI  - Mortality and morbidity after spinal surgery in patients with Parkinson's
      disease: a retrospective matched-pair cohort study.
AB  - BACKGROUND CONTEXT: There is a lack of information about postoperative outcomes
      and related risk factors associated with spinal surgery in patients with
      Parkinson's disease (PD). PURPOSE: This study aimed to investigate the
      postoperative morbidity and mortality associated with spinal surgery for patients
      with PD, and the risk factors for poor outcomes. STUDY DESIGN: This is a
      retrospective matched-pair cohort study. PATIENT SAMPLE: Data of patients who
      underwent elective spinal surgery between July 2010 and March 2013 were extracted
      from the Diagnosis Procedure Combination database, a nationwide inpatient
      database in Japan. OUTCOME MEASURES: In-hospital mortality and occurrence of
      postoperative complications. METHODS: For each patient with PD, we randomly
      selected up to four age- and sex-matched controls in the same hospital in the
      same year. The differences in in-hospital mortality and occurrence of
      postoperative complications were compared between patients with PD and controls.
      A multivariable logistic regression model fitted with a generalized estimation
      equation was used to identify significant predictors of major complications
      (surgical site infection, sepsis, pulmonary embolism, respiratory complications,
      cardiac events, stroke, and renal failure). Multiple imputation was used for
      missing data. RESULTS: Among 154,278 patients undergoing spinal surgery, 1,423
      patients with PD and 5,498 matched controls were identified. Crude in-hospital
      mortality was higher in patients with PD than in controls (0.8% vs. 0.3%,
      respectively). The crude proportion of major complications was also higher in
      patients with PD (9.8% vs. 5.1% in controls). Postoperative delirium was more
      common in patients with PD (30.3%) than in controls (4.3%). Parkinson's disease
      was a significant predictor of major postoperative complications, even after
      adjusting for other risk factors (odds ratio, 1.74; 95% confidence intervals,
      1.37-2.22; p<.001). CONCLUSIONS: Patients with PD had a significantly increased
      risk of postoperative complications following spinal surgery. Postoperative
      delirium was the most frequently observed complication.

PMID- 27884744
TI  - Technical description of oblique lateral interbody fusion at L1-L5 (OLIF25) and
      at L5-S1 (OLIF51) and evaluation of complication and fusion rates.
AB  - BACKGROUND CONTEXT: The oblique lateral interbody fusion (OLIF) procedure is
      aimed at mitigating some of the challenges seen with traditional anterior lumbar
      interbody fusion (ALIF) and transpsoas lateral lumbar interbody fusion (LLIF),
      and allows for interbody fusion at L1-S1. PURPOSE: The study aimed to describe
      the OLIF technique and assess the complication and fusion rates. STUDY DESIGN:
      This is a retrospective cohort study. PATIENT SAMPLE: The sample is composed of
      137 patients who underwent OLIF procedure. OUTCOME MEASURES: The outcome measures
      were adverse events within 6 months of surgery: infection, symptomatic
      pseudarthrosis, hardware failure, vascular injury, perioperative blood
      transfusion, ureteral injury, bowel injury, renal injury, prolonged postoperative
      ileus (more than 3 days), incisional hernia, pseudohernia, reoperation,
      neurologic deficits (weakness, numbness, paresthesia), hip flexion pain,
      retrograde ejaculation, sympathectomy affecting lower extremities, deep vein
      thrombosis, pulmonary embolism, myocardial infarction, pneumonia, and
      cerebrovascular accident. The outcome measures also include fusion and subsidence
      rates based on computed tomography (CT) done at 6 months postoperatively.
      METHODS: Retrospective chart review of 150 consecutive patients was performed to
      examine the complications associated with OLIF at L1-L5 (OLIF25), OLIF at L5-S1
      (OLIF51), and OLIF at L1-L5 combined with OLIF at L5-S1 (OLIF25+OLIF51). Only
      patients who had at least 6 months of postoperative follow-up, including CT scan
      at 6 months after surgery, were included. Independent radiology review of CT data
      was performed to assess fusion and subsidence rates at 6 months. RESULTS: A total
      of 137 patients underwent fusion at 340 levels. An overall complication rate of
      11.7% was seen. The most common complications were subsidence (4.4%),
      postoperative ileus (2.9%), and vascular injury (2.9%). Ileus and vascular
      injuries were only seen in cases including OLIF51. No patient suffered neurologic
      injury. No cases of ureteral injury, sympathectomy affecting the lower
      extremities, or visceral injury were seen. Successful fusion was seen at 97.9% of
      surgical levels. CONCLUSIONS: Oblique lateral interbody fusion is a safe
      procedure at L1-L5 as well as L5-S1. The complication profile appears acceptable
      when compared with LLIF and ALIF. The oblique trajectory mitigates psoas muscle
      and lumbosacral plexus-related complications seen with the lateral transpsoas
      approach. Furthermore, there is a high fusion rate based on CT data at 6 months.

PMID- 27884745
TI  - Increase in spinal deformity surgery in patients age 60 and older is not
      associated with increased complications.
AB  - BACKGROUND CONTEXT: Surgical treatment for adult spinal deformity improves
      patient quality of life; however, trends in surgical utilization in the elderly,
      who may be at higher risk for complications, remain unclear. PURPOSE: To identify
      trends in the utilization of adult deformity and determine complication rates
      among older patients. STUDY DESIGN: This is a retrospective database analysis.
      PATIENT SAMPLE: The Nationwide Inpatient Sample database was queried from 2004 to
      2011 to identify adult patients who underwent spinal fusion of eight or more
      levels using International Classification of Diseases, Ninth Revision (ICD-9)
      coding. OUTCOME MEASURES: Incidence of surgery, complication rates, length of
      stay, and total hospital charges. METHODS: The incidence of surgery was
      normalized to United States census data by age group. Trends in complications,
      length of stay, and inflation-adjusted hospital charges were determined using
      linear regression and Cochran-Armitage trend testing. RESULTS: An estimated
      29,237 patients underwent adult spinal deformity surgery with an increase from
      2,137 to 5,030 cases per year from 2004 to 2011. Surgical incidence among
      patients 60 years and older increased from 1.9 to 6.5 cases per 100,000 people
      from 2004 to 2011 (p<.001), whereas utilization in patients younger than 60
      increased from 0.59 to 0.93. Linear regression revealed that the largest increase
      in surgical utilization was for patients aged 65-69 years with an increase of
      0.68 patients per 100,000 people per year (p<.001), followed by patients aged 70
      74 years with a rate of 0.56 patients per 100,000 people per year (p=.001).
      Overall complication rates were 22.5% in 2004 and 26.7% in 2011. Although
      complication risk increased with age (>=60 vs. <60: relative risk 1.91 [1.83,
      1.99], p<.001), within-age group rates were stable over time. Mean length of stay
      was 9.6 days in 2004 and 9.0 days in 2011. Inflation-adjusted mean hospital
      charges increased from $171,517 in 2004 to $303,479 in 2011 (p<.001).
      CONCLUSIONS: Operative management of adult spinal deformity increased 3.4-fold
      among patients >=60 years from 2004 to 2011, with an associated 1.8-fold increase
      in hospital charges. Although the exact reasons for the striking increase in
      hospital charges remain unclear, some of the increase is likely related to
      decreasing reimbursement of charges by payors over the same period of time. The
      large majority of cases were performed in large academic centers, and growth in
      deformity trained spine specialists in these centers may have contributed to this
      trend. Despite the increased utilization of surgery for adult spinal deformity,
      in-hospital complications remained stable across all ages.

PMID- 27884747
TI  - Novel function of alpha1D L-type calcium channel in the atria.
AB  - Ca entry through atrial L-type Calcium channels (alpha1C and alpha1D) play an
      important role in muscular contraction, regulation of gene expression, and
      release of hormones including atrial natriuretic peptide (ANP), and brain
      natriuretic peptide (BNP). alpha1D Ca channel is exclusively expressed in atria,
      and has been shown to play a key role in the pathogenesis of atrial fibrillation.
      Recent data have shown that the small conductance calcium-activated potassium
      channel, SK4 is also atrial specific and also contributes prominently to the
      secretion of ANP and BNP. However, its functional role in the heart is still
      poorly understood. Here we used alpha1D gene heterozygous (alpha1D+/-) mice and
      HL-1 cells to determine the functional contribution of SK4 channels to alpha1D
      dependent regulation of ANP and BNP secretion in response to endothelin (ET),
      and/or mechanical stretch. Immunoprecipitation with alpha1D specific antibody and
      western blotting with SK4 specific antibody on the immuno-precipitated protein
      complex showed a band at 50 KDa confirming the presence of SK4 in the complex and
      provided evidence of interaction between SK4 and alpha1D channels. Using RT-PCR,
      we observed a 2.9 fold decrease in expression of Cacna1d (gene encoding alpha1D)
      mRNA in atria from alpha1D+/-mice. The decrease in alpha1D mRNA corresponded with
      a 4.2 fold decrease in Kcnn4 (gene encoding SK4) mRNA from alpha1D+/- mice. These
      changes were paralleled with a 77% decrease in BNP serum levels from alpha1D+/-
      mice. When alpha1D was knocked down in HL-1cardiomyocytes using CRISPR/Cas9
      technology, a 97% decrease in secreted BNP was observed even in cells subjected
      to stretch and endothelin. In conclusion, our data are first to show that alpha1D
      Ca and SK4 channels are coupled in the atria, and that deletion of alpha1D leads
      to decreased SK4 mRNA and BNP secretion providing evidence for a novel role of
      alpha1D in atrial endocrine function. Elucidating the regulatory factors that
      underlie the secretory function of atria will identify novel therapeutic targets
      for treatment and prevention of cardiac arrhythmias such as atrial fibrillation.

PMID- 27884746
TI  - Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB).
AB  - Neglected disease drug discovery is generally poorly funded compared with major
      diseases and hence there is an increasing focus on collaboration and
      precompetitive efforts such as public-private partnerships (PPPs). The More
      Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by
      the EU with the goal of discovering new drugs for tuberculosis. Collaborative
      Drug Discovery has provided a commercial web-based platform called CDD Vault
      which is a hosted collaborative solution for securely sharing diverse chemistry
      and biology data. Using CDD Vault alongside other commercial and free
      cheminformatics tools has enabled support of this and other large collaborative
      projects, aiding drug discovery efforts and fostering collaboration. We will
      describe CDD's efforts in assisting with the MM4TB project.

PMID- 27884748
TI  - Isolation of bacterial strains able to degrade biphenyl, diphenyl ether and the
      heat transfer fluid used in thermo-solar plants.
AB  - Thermo-solar plants use eutectic mixtures of diphenyl ether (DE) and biphenyl
      (BP) as heat transfer fluid (HTF). Potential losses of HTF may contaminate soils
      and bioremediation is an attractive tool for its treatment. DE- or BP-degrading
      bacteria are known, but up to now bacteria able to degrade HTF mixture have not
      been described. Here, five bacterial strains which are able to grow with HTF or
      its separate components DE and BP as sole carbon sources have been isolated,
      either from soils exposed to HTF or from rhizospheric soils of plants growing
      near a thermo-solar plant. The organisms were identified by 16S rRNA gene
      sequencing as Achromobacter piechaudii strain BioC1, Pseudomonas plecoglossicida
      strain 6.1, Pseudomonas aeruginosa strains HBD1 and HBD3, and Pseudomonas
      oleovorans strain HBD2. Activity of 2,3-dihydroxybiphenyl dioxygenase (BphC), a
      key enzyme of the biphenyl upper degradation pathway, was detected in all
      isolates. Pseudomonas strains almost completely degraded 2000ppm HTF after 5-day
      culture, and even tolerated and grew in the presence of 150,000ppm HTF, being
      suitable candidates for in situ soil bioremediation. Degradation of both
      components of HTF is of particular interest since in the DE-degrader Sphingomonas
      sp. SS3, growth on DE or benzoate was strongly inhibited by addition of BP.

PMID- 27884749
TI  - Celecoxib exerts antitumor effects in HL-60 acute leukemia cells and inhibits
      autophagy by affecting lysosome function.
AB  - Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated
      to exert antitumor activity in a variety of cancer cells. The underlying
      mechanism involves inhibition of cell cycle progression and induction of
      apoptosis. Besides, celecoxib has also been found to induce autophagy in some
      solid tumor cells. The aim of this study was to investigate the effect of
      celecoxib on cell proliferation in HL-60 human acute leukemia cells and to
      explore the potential mechanism. HL-60 cells were exposed to various
      concentrations of celecoxib and cell viability was evaluated by the MTT assay.
      Apoptosis was analyzed with flow cytometry and the amount of autophagosome was
      evaluated by LysoTracker probe labelling. The expression of apoptosis- and
      autophagy-related proteins was assayed by Western blot and LysoSensor probe
      labelling was used to detect the effect of celecoxib on the lysosomal functions.
      The results of this study indicated that celecoxib inhibited cell proliferation
      in a time- and dose-dependent fashion. The flow cytometry analysis showed that
      celecoxib induced apoptosis at low concentrations and mainly cell necrosis at
      high concentrations. The Western blot test confirmed the induction of apoptosis
      by the upregulation of apoptosis-related proteins cleaved caspase-3 and cleaved
      PARP. Furthermore, this study demonstrated that celecoxib prevented the
      autophagic flux by inhibiting lysosome function; the fluorescence intensity of
      the LysoTracker probe and the level of autophagy-related proteins LC3-II and p62
      were increased, but the fluorescence intensity of the LysoSensor probe was
      weakened. These findings show that celecoxib is an autophagy suppresser and has
      antitumor effects in HL-60 cells by inducing cell apoptosis and necrosis.

PMID- 27884750
TI  - Methylprednisolone improves lactate metabolism through reduction of elevated
      serum lactate in rat model of multiple sclerosis.
AB  - BACKGROUND: Some studies have demonstrated elevated concentrations of lactate
      both in the cerebrospinal fluid (CSF) and blood samples of multiple sclerosis
      (MS) patients as a pathological condition. We designed an experimental study
      first to investigate the serum level of lactate as a biomarker of MS progression
      and also to investigate the effect of methylprednisolone on serum lactate.
      METHODS: Experimental autoimmune encephalomyelitis (EAE) was inducted in Lewis
      rats, and then rats were treated intraperitoneally with methylprednisolone
      (30mg/kg/d), at the disease onset, and the clinical scores were recorded. After
      seven days of treatment, the serum levels of lactate were determined using high
      performance liquid chromatography (HPLC). Moreover, lymphocyte infiltration and
      the demyelinated area was analysed in spinal cord. RESULTS: Compared to the
      untreated-EAE rats, methylprednisolone remarkably improved the clinical score of
      EAE and ameliorated the spinal cord inflammation and demyelination. In addition,
      the marked decline in IFN-gamma and the increase in IL-4 confirmed improvement in
      the rats treated with methylprednisolone. Measurement of lactate using HPLC
      indicated enhancement in the serum level of lactate in the untreated-EAE rats;
      the lactate level significantly decreased after methylprednisolone therapy.
      Moreover, serum lactates and disease severity were correlated positively and
      significantly. CONCLUSION: These data confirmed for the first time, that
      methylprednisolone can decreases the enhanced level of serum lactate in EAE
      model. In addition, it was shown that measurement of serum lactate could be an
      inexpensive and accurate laboratory test to determine the response to treatment
      and to assess disease severity in MS patients.

PMID- 27884751
TI  - A systematic review of the effect of cannabidiol on cognitive function: Relevance
      to schizophrenia.
AB  - BACKGROUND AND OBJECTIVES: Cognitive impairment is a core symptom domain of
      schizophrenia, neurological disorders and substance abuse. It is characterised by
      deficits in learning, memory, attention and executive functioning and can
      severely impact daily living. Antipsychotic drugs prescribed to treat
      schizophrenia provide limited cognitive benefits and novel therapeutic targets
      are required. Cannabidiol (CBD), a component of the cannabis plant, has anti
      inflammatory and antipsychotic-like properties; however, its ability to improve
      cognitive impairment has not been thoroughly explored. The aim of this systematic
      review was to evaluate preclinical and clinical literature on the effects of CBD
      in cognitive domains relevant to schizophrenia. METHODS: A systematic literature
      search was performed across numerous electronic databases for English language
      articles (January 1990-March 2016), with 27 articles (18 preclinical and 9
      clinical studies) included in the present review. RESULTS: CBD improves cognition
      in multiple preclinical models of cognitive impairment, including models of
      neuropsychiatric (schizophrenia), neurodegenerative (Alzheimer's disease), neuro
      inflammatory (meningitis, sepsis and cerebral malaria) and neurological disorders
      (hepatic encephalopathy and brain ischemia). To date, there is one clinical
      investigation into the effects of CBD on cognition in schizophrenia patients,
      with negative results for the Stroop test. CBD attenuates Delta9-THC-induced
      cognitive deficits. CONCLUSIONS: The efficacy of CBD to improve cognition in
      schizophrenia cannot be elucidated due to lack of clinical evidence; however,
      given the ability of CBD to restore cognition in multiple studies of impairment,
      further investigation into its efficacy in schizophrenia is warranted. Potential
      mechanisms underlying the efficacy of CBD to improve cognition are discussed.

PMID- 27884752
TI  - Quantitative proteomic analysis reveals that proteins required for fatty acid
      metabolism may serve as diagnostic markers for gastric cancer.
AB  - BACKGROUND: Gastric cancer is one of the leading causes of cancer-related deaths
      worldwide. The sensitivities and specificities of current biomarkers for gastric
      cancer are insufficient for clinical detection, and new diagnostic tests are
      therefore urgently required. METHODS: A discovery set of gastric cancer and
      adjacent normal tissues were analyzed for differentially expressed proteins by
      labeling of peptide digests with isobaric tag for relative and absolute
      quantitation (iTRAQ) reagents followed by liquid chromatography-electrospray
      ionization-tandem mass spectrometry. A validation set of 70 pairs of gastric
      cancer and adjacent normal tissues were examined to confirm the expression levels
      of the potential biomarkers identified by iTRAQ labeling. RESULTS: We detected
      431 proteins associated with 16 KEGG pathways that were differentially expressed
      in gastric cancer tissues, of which 224 were upregulated and 207 were
      downregulated in gastric cancer tissues. Coexpression of fatty acid binding
      protein (FABP1) and fatty acid synthase (FASN) in gastric cancer tissues (61.4%
      sensitivity and 77.1% specificity) was strongly associated with lymph node
      metastasis and Tumor, Node, Metastasis stage I/II. CONCLUSION: Quantitative
      proteomic analysis of gastric cancer tissues revealed that coexpression of FABP1
      and FASN may serve as a biomarker for detection of early gastric cancer.

PMID- 27884754
TI  - Increased serum concentrations of asymmetric dimethylarginine (ADMA) in patients
      with early-onset coronary artery disease.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA) has been associated with an
      increased risk of cardiovascular disease. We investigated the role of serum ADMA
      concentrations in early-onset coronary artery disease (EOCAD). METHODS:
      Candidates for coronary artery angiography (age<50y for men and <55y for women)
      who met the inclusion criteria were enrolled in this study. Serum concentrations
      of ADMA were determined using ELISA. Severity of coronary atherosclerosis was
      estimated by number of diseased vessels. RESULTS: A total of 601 subjects (286
      with EOCAD patients and 315 controls) were included in the study. ADMA
      concentrations were found to be significantly higher in the EOCAD group (0.480+/
      0.110MUmol/l) than in the control group (0.457+/-0.091, P=0.007). ADMA
      concentrations significantly increased with the number of diseased vessels
      (P<0.001). In addition, serum ADMA concentrations were affected by diabetes
      mellitus and smoking status, and were positively correlated with serum creatinine
      and body mass index (BMI). CONCLUSIONS: Our results show that serum ADMA
      concentrations were associated with the presence and severity of EOCAD,
      suggesting that ADMA may be involved in the progression of EOCAD.

PMID- 27884753
TI  - Cell-free DNA induced apoptosis of granulosa cells by oxidative stress.
AB  - BACKGROUND: Cell-free DNA is a DNA fragment that is produced by cell apoptosis
      which can affect the micro-environment of cell apoptosis. The levels of Cell-free
      DNA have been associated with successful rate of in vitro fertilization-embryo
      transfer (IVF-ET) and embryonic development. Our aim is to determine the
      relationship between cell-free DNA and embryo quality. The mechanisms of cell
      free DNA in granulose and the apoptosis will be determined also. METHODS: The
      study enrolled patients who were undergone IVF for the first time and grouped the
      patients as pregnant (n=130) and non-pregnant (n=59). The relationship was
      determined by statistical analysis between the levels of cell-free DNA in the
      follicular fluid and clinical data of IVF patients. Flow cytometry was done to
      detect the rate of granulosa cell apoptosis and intracellular reactive oxygen
      species (ROS) level. Western blotting and fluorescent quantitative PCR detected
      the apoptosis-related gene expressions. RESULTS: Clinical data statistics showed
      that cell-free DNA levels were positively correlated with granulosa cell
      apoptosis and negatively correlated with embryo quality and pregnancy rates. High
      levels of cell-free DNA lead to increased ROS in granulosa cells and activated
      caspase through Fas/FasL that induced apoptosis. CONCLUSION: High levels of cell
      free DNA triggers granulosa cell apoptosis and influences oocyte maturation
      embryo development and pregnancy rates in IVF treatments. Cell-free DNA can be as
      a secondary criteria and predictive marker for the quality control of IVF embryo.

PMID- 27884756
TI  - Repeated unpredictable threats without harm impair spatial working memory in the
      Barnes maze.
AB  - Psychological stressors elicit the anticipation of homeostatic challenge, whereas
      physical stressors are direct threats to homeostasis. Many rodent models of
      stress include both types of stressors, yet deficits, like those reported for
      working memory, are often attributed to psychological stress. To empirically test
      whether intermittent psychological stressors, such as repeated threats, are
      solely sufficient to impair spatial working memory, we developed a novel rodent
      model of stress that is restricted to the anticipation of threat, and free of
      direct physical challenge. Adolescent male Sprague-Dawley rats were randomly
      assigned to control (CT) or stress (ST) housing conditions consisting of two tub
      cages, one with food and another with water, separated by a tunnel. Over three
      weeks (P31-P52), the ST group received random (probability of 0.25), simultaneous
      presentations of ferret odor, and abrupt lights, and sound at the center of the
      tunnel. Relative to the CT group, the ST group had consistently fewer tunnel
      crossings, consistent with avoidance of a psychological stressor. Both groups had
      similar body weights and crossed the tunnel more in the dark than light period.
      Three days after removal from the treatment conditions, spatial working memory
      was tested on the Barnes maze. The ST group displayed deficits in spatial working
      memory, including longer latencies to enter the goal box position, and a greater
      number of returns to incorrect holes, but no significant differences in speed.
      Memory can be affected by sleep disruption, and sleep can be affected by stress.
      Circadian activity patterns in the tunnels were similar across groups. Therefore,
      the data suggest that intermittent threats without physical stress are sufficient
      to impair spatial working memory in adolescence.

PMID- 27884755
TI  - 64Cu-PSMA uptake in meningioma: A potential pitfall of a promising radiotracer.

PMID- 27884758
TI  - Magnesium enhances opioid-induced analgesia - What we have learnt in the past
      decades?
AB  - Opioids are increasingly used in alleviating pain, including cancer-related pain
      and postoperative pain. Unfortunately, the development of tolerance, the
      resistance of neuropathic pain on opioid analgesia or other undesirable effects
      may limit their utility. In order to reduce opioid doses, and thereby to avoid
      the risk of side effects and sudden deaths due to overdosing, attempts have been
      made to introduce co-analgesics. Due to an increasing amount of data concerning a
      potential enhance of opioid analgesia by the physiological antagonist of N-methyl
      d-aspartate receptors, magnesium ions (Mg2+), a concomitant use of such a
      combination seems to be interesting from a clinical point of view. Therefore, the
      aim of this review is to provide an analysis of existing preclinical and clinical
      studies in the context of the benefits of using this combination in clinical
      practice. A potential mechanism of magnesium - opioid interaction is also
      suggested. The potential influence of Mg on opioid adverse/side effects as well
      as conclusions on the safety of combined administration of magnesium and opioid
      drugs were also summarized. Data from animal studies indicate that magnesium
      increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well
      as acute pain. In clinical trials, most authors confirmed that magnesium reduces
      opioid consumption and alleviates postoperative pain scores while not increasing
      the risk of side effects after opioids. However, more clinical studies are needed
      concerning an influence of Mg on opioid activity in other difficult to treat
      types of pain, especially neuropathic and inflammatory.

PMID- 27884757
TI  - The role of hearing ability and speech distortion in the facilitation of
      articulatory motor cortex.
AB  - Excitability of articulatory motor cortex is facilitated when listening to speech
      in challenging conditions. Beyond this, however, we have little knowledge of what
      listener-specific and speech-specific factors engage articulatory facilitation
      during speech perception. For example, it is unknown whether speech motor
      activity is independent or dependent on the form of distortion in the speech
      signal. It is also unknown if speech motor facilitation is moderated by hearing
      ability. We investigated these questions in two experiments. We applied
      transcranial magnetic stimulation (TMS) to the lip area of primary motor cortex
      (M1) in young, normally hearing participants to test if lip M1 is sensitive to
      the quality (Experiment 1) or quantity (Experiment 2) of distortion in the speech
      signal, and if lip M1 facilitation relates to the hearing ability of the
      listener. Experiment 1 found that lip motor evoked potentials (MEPs) were larger
      during perception of motor-distorted speech that had been produced using a tongue
      depressor, and during perception of speech presented in background noise,
      relative to natural speech in quiet. Experiment 2 did not find evidence of motor
      system facilitation when speech was presented in noise at signal-to-noise ratios
      where speech intelligibility was at 50% or 75%, which were significantly less
      severe noise levels than used in Experiment 1. However, there was a significant
      interaction between noise condition and hearing ability, which indicated that
      when speech stimuli were correctly classified at 50%, speech motor facilitation
      was observed in individuals with better hearing, whereas individuals with
      relatively worse but still normal hearing showed more activation during
      perception of clear speech. These findings indicate that the motor system may be
      sensitive to the quantity, but not quality, of degradation in the speech signal.
      Data support the notion that motor cortex complements auditory cortex during
      speech perception, and point to a role for the motor cortex in compensating for
      differences in hearing ability.

PMID- 27884759
TI  - Heterodimerisation between VEGFR-1 and VEGFR-2 and not the homodimers of VEGFR-1
      inhibit VEGFR-2 activity.
AB  - Vascular endothelial growth factor (VEGF) signaling is tightly regulated by
      specific VEGF receptors (VEGF-R). Recently, we identified heterodimerisation
      between VEGFR-1 and VEGFR-2 (VEGFR1-2) to regulate VEGFR-2 function. However,
      both the mechanism of action and the relationship with VEGFR-1 homodimers remain
      unknown. The current study shows that activation of VEGFR1-2, but not VEGFR-1
      homodimers, inhibits VEGFR-2 receptor phosphorylation under VEGF stimulation in
      human endothelial cells. Furthermore, inhibition of phosphatidylinositol 3-kinase
      (PI3K) increases VEGFR-2 phosphorylation under VEGF stimulation. More
      importantly, inhibition of PI3K pathway abolishes the VEGFR1-2 mediated
      inhibition of VEGFR-2 phosphorylation. We further demonstrate that inhibition of
      PI3K pathway promotes capillary tube formation. Finally, the inhibition of PI3K
      abrogates the inhibition of in vitro angiogenesis mediated by VEGFR1-2
      heterodimers. These findings demonstrate that VEGFR1-2 heterodimers and not VEGFR
      1 homodimers inhibit VEGF-VEGFR-2 signaling by suppressing VEGFR-2
      phosphorylation via PI3K pathway.

PMID- 27884760
TI  - Marine n-3 fatty acids and the risk of new-onset postoperative atrial
      fibrillation after cardiac surgery.

PMID- 27884762
TI  - Pleasantness, familiarity, and identification of spice odors are interrelated and
      enhanced by consumption of herbs and food neophilia.
AB  - The primary dimension of odor is pleasantness, which is associated with a
      multitude of factors. We investigated how the pleasantness, familiarity, and
      identification of spice odors were associated with each other and with the use of
      the respective spice, overall use of herbs, and level of food neophobia. A total
      of 126 adults (93 women, 33 men; age 25-61 years, mean 39 years) rated the odors
      from 12 spices (oregano, anise, rosemary, mint, caraway, sage, thyme, cinnamon,
      fennel, marjoram, garlic, and clove) for pleasantness and familiarity, and
      completed a multiple-choice odor identification. Data on the use of specific
      spices, overall use of herbs, and Food Neophobia Scale score were collected using
      an online questionnaire. Familiar odors were mostly rated as pleasant (except
      garlic), whereas unfamiliar odors were rated as neutral (r = 0.63). We observed
      consistent and often significant trends that suggested the odor pleasantness and
      familiarity were positively associated with the correct odor identification,
      consumption of the respective spice, overall use of herbs, and food neophilia.
      Our results suggest that knowledge acquisition through repetitive exposure to
      spice odor with active attention may gradually increase the odor pleasantness
      within the framework set by the chemical characteristics of the aroma compound.

PMID- 27884761
TI  - Assessment of the motivation to use artificial sweetener among individuals with
      an eating disorder.
AB  - Eating disorders are associated with a range of abnormalities in eating behavior.
      Some individuals consume large amounts of non-caloric artificial sweeteners,
      suggesting abnormalities in appetitive responding. The current study aimed to
      quantify hedonic and motivating effects of artificial sweetener in individuals
      with and without an eating disorder. Two laboratory studies were conducted.
      Hedonic preference was estimated using the number of artificial sweetener packets
      (0-10) added to unsweetened cherry flavored Kool-Aid (study 1). Motivation to
      obtain sweetener was assessed by a progressive ratio (PR) work task (study 2).
      Ninety-three participants (25 anorexia nervosa restricting type (AN-R), 23 AN
      binge/purge type (AN-B/P), 20 bulimia nervosa (BN), and 25 normal controls (NC))
      completed the study. No significant difference in hedonic preference was found
      among participant groups. Work completed at the PR task ranged from 0 to 9500 key
      board presses. The AN-B/P group had a significantly higher breakpoint and
      performed significantly more work for sweetener compared to the BN and NC groups.
      Among AN-B/P and AN-R participants, the preferred number of Equal packets was
      significantly correlated with the breakpoint and total work. The increased amount
      of work for sweetener among individuals with AN-B/P supports an enhanced reward
      value of sweet taste in this population, and suggests that the characteristic
      food avoidance in AN cannot be accounted for by decreased reward value of all
      taste-related stimuli. This study also supports the novel application of a PR
      ratio task to quantify the motivating effect of sweet taste among individuals
      with an eating disorder.

PMID- 27884764
TI  - Targeted direct-acting antiviral treatment for chronic hepatitis C: A financial
      reality or an obstacle to elimination?

PMID- 27884763
TI  - ACOX2 deficiency: An inborn error of bile acid synthesis identified in an
      adolescent with persistent hypertransaminasemia.
AB  - BACKGROUND & AIMS: Acyl-CoA oxidase (ACOX2) is involved in the shortening of C27
      cholesterol derivatives to generate C24 bile acids. Inborn errors affecting the
      rest of peroxisomal enzymes involved in bile acid biosynthesis have been
      described. Here we aimed at investigating the case of an adolescent boy with
      persistent hypertransaminasemia of unknown origin and suspected dysfunction in
      bile acid metabolism. METHODS: Serum and urine samples were taken from the
      patient, his sister and parents and underwent HPLC-MS/MS and HPLC-TOF analyses.
      Coding exons in genes of interest were amplified by high-fidelity PCR and
      sequenced. Wild-type or mutated (mutACOX2) variants were overexpressed in human
      hepatoblastoma HepG2 cells to determine ACOX2 enzymatic activity, expression and
      subcellular location. RESULTS: The patient's serum and urine showed negligible
      amounts of C24 bile acids, but augmented levels of C27 intermediates, mainly
      tauroconjugated trihydroxycholestanoic acid (THCA). Genetic analysis of enzymes
      potentially involved revealed a homozygous missense mutation (c.673C>T; R225W) in
      ACOX2. His only sister was also homozygous for this mutation and exhibited
      similar alterations in bile acid profiles. Both parents were heterozygous and
      presented normal C24 and C27 bile acid levels. Immunofluorescence studies showed
      similar protein size and peroxisomal localization for both normal and mutated
      variants. THCA biotransformation into cholic acid was enhanced in cells
      overexpressing ACOX2, but not in those overexpressing mutACOX2. Both cell types
      showed similar sensitivity to oxidative stress caused by C24 bile acids. In
      contrast, THCA-induced oxidative stress and cell death were reduced by
      overexpressing ACOX2, but not mutACOX2. CONCLUSION: ACOX2 deficiency, a condition
      characterized by accumulation of toxic C27 bile acid intermediates, is a novel
      cause of isolated persistent hypertransaminasemia. LAY SUMMARY: Elevation of
      serum transaminases is a biochemical sign of liver damage due to multiplicity of
      causes (viruses, toxins, autoimmunity, metabolic disorders). In rare cases the
      origin of this alteration remains unknown. We have identified by the first time
      in a young patient and his only sister a familiar genetic defect of an enzyme
      called ACOX2, which participates in the transformation of cholesterol into bile
      acids as a cause of increased serum transaminases in the absence of any other
      symptomatology. This treatable condition should be considered in the diagnosis of
      those patients where the cause of elevated transaminases remains obscure.

PMID- 27884765
TI  - Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of
      Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized,
      Controlled, Phase IIb/III Trial.
AB  - BACKGROUND: Influenza causes excessive hospitalizations and deaths. The study
      assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir
      combination for treatment of serious influenza. METHODS: From February to April
      2015, we conducted a prospective open-label, randomized, controlled trial. Adult
      patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day
      combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg
      twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice
      daily without placebo for 5 days as a control method (1:1). The primary end point
      was 30-day mortality. The secondary end points were 90-day mortality, serial
      nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor
      resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and
      duration of hospital stay. RESULTS: Among the 217 patients with influenza A(H3N2)
      enrolled, 107 were randomly assigned to the combination treatment. The median age
      was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died
      during the 30-day follow-up. The combination treatment was associated with lower
      30-day mortality (P = .01), less frequent high dependency unit admission (P =
      .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3;
      P < .01) and the NPA specimens with NIRV quasispecies >= 5% (days 1-2; P < .01)
      were significantly lower in the combination treatment group. Multivariate
      analysis showed that combination treatment was the only independent factor
      associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04).
      CONCLUSIONS: Combination treatment reduced both 30- and 90-day mortality and
      length of hospital stay. Further study of the antiviral and immunomodulatory
      effects of this combination treatment of severe influenza is warranted. TRIAL
      REGISTRY: BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL:
      www.isrctn.com/ISRCTN11273879.

PMID- 27884767
TI  - EIF2AK4 Mutations in Patients Diagnosed With Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary
      capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension
      (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important
      clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase
      4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause
      HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4
      mutations in patients diagnosed clinically with IPAH or HPAH. METHODS: Sanger
      sequencing and deletion/duplication analysis were performed to detect mutations
      in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients
      diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n =
      9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in
      four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients
      negative for mutations in all known PAH genes (n = 66) were then sequenced for
      mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and
      reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations.
      RESULTS: Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients
      with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4
      mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with
      HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with
      severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic
      EIF2AK4 mutations. CONCLUSIONS: Pathogenic biallelic EIF2AK4 mutations are rarely
      identified in patients diagnosed with HPAH. Identification of pathogenic
      biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from
      heritable PVOD or PCH.

PMID- 27884766
TI  - Mechanisms of Vascular Dysfunction in COPD and Effects of a Novel Soluble Epoxide
      Hydrolase Inhibitor in Smokers.
AB  - BACKGROUND: Smoking and COPD are risk factors for cardiovascular disease, and the
      pathogenesis may involve endothelial dysfunction. We tested the hypothesis that
      endothelium-derived epoxyeicosatrienoic acid (EET)-mediated endothelial function
      is impaired in patients with COPD and that a novel soluble epoxide hydrolase
      inhibitor, GSK2256294, attenuates EET-mediated endothelial dysfunction in human
      resistance vessels both in vitro and in vivo. METHODS: Endogenous and stimulated
      endothelial release of EETs was assessed in 12 patients with COPD, 11 overweight
      smokers, and two matched control groups, using forearm plethysmography with
      intraarterial infusions of fluconazole, bradykinin, and the combination. The
      effects of GSK2256294 on EET-mediated vasodilation in human resistance arteries
      were assessed in vitro and in vivo in a phase I clinical trial in healthy
      overweight smokers. RESULTS: Compared with control groups, there was reduced
      vasodilation with bradykinin (P = .005), a blunted effect of fluconazole on
      bradykinin-induced vasodilation (P = .03), and a trend toward reduced basal
      EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD (P = .08). A
      similar pattern was observed in overweight smokers. In vitro, 10 MUM GSK2256294
      increased 11,12-EET-mediated vasodilation compared with vehicle (90% +/- 4.2% vs
      72.6% +/- 6.2% maximal dilatation) and shifted the bradykinin half-maximal
      effective concentration (EC50) (-8.33 +/- 0.172 logM vs -8.10 +/- 0.118 logM; P =
      .001 for EC50). In vivo, 18 mg GSK2256294 improved the maximum bradykinin
      response from 338% +/- 46% before a dose to 566% +/- 110% after a single dose (P
      = .02) and to 503% +/- 123% after a chronic dose (P = .003). CONCLUSIONS:
      GSK2256294 attenuates smoking-related EET-mediated endothelial dysfunction,
      suggesting potential therapeutic benefits in patients with COPD. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01762774; URL: www.clinicaltrials.gov.

PMID- 27884768
TI  - Intact renewal after extinction of conditioned suppression with lesions of either
      the retrosplenial cortex or dorsal hippocampus.
AB  - Extinction of fear to a Pavlovian conditioned stimulus (CS) is known to be
      context-specific. When the CS is tested outside the context of extinction, fear
      returns, or renews. Several studies have demonstrated that renewal depends upon
      the hippocampus, although there are also studies where renewal was not impacted
      by hippocampal damage, suggesting that under some conditions context encoding
      and/or retrieval of extinction depends upon other regions. One candidate region
      is the retrosplenial cortex (RSC), which is known to contribute to contextual and
      spatial learning and memory. Using a conditioned-suppression paradigm, Experiment
      1 tested the impact of pre-training RSC lesions on renewal of extinguished fear.
      Consistent with previous studies, lesions of the RSC did not impact acquisition
      or extinction of conditioned fear to the CS. Further, there was no evidence that
      RSC lesions impaired renewal, indicating that contextual encoding and/or
      retrieval of extinction does not depend upon the RSC. In Experiment 2, post
      extinction lesions of either the RSC or dorsal hippocampus (DH) also had no
      impact on renewal. However, in Experiment 3, both RSC and DH lesions did impair
      performance in an object-in-place procedure, an index of place memory. RSC and DH
      contributions to extinction and renewal are discussed.

PMID- 27884770
TI  - Neutrophil granulocytes in cerebral ischemia - Evolution from killers to key
      players.
AB  - Neutrophil granulocytes (or polymorphonuclear cells, PMNs) have long been
      considered as crude killing machines, particularly trained to attack bacterial or
      fungal pathogens in wounds or infected tissues. That perspective has
      fundamentally changed over the last decades, as PMNs have been shown to exert a
      livery exchange between other cells of the innate and adaptive immune system.
      PMNs do provide major immunomodulatory contribution during acute inflammation and
      subsequent clearance. Following sterile inflammation like cerebral ischemia, PMNs
      are among the first hematogenous cells attracted to the ischemic tissue. As
      inflammation is a crucial component within stroke pathophysiology, several
      studies regarding the role of PMNs following cerebral ischemia have been carried
      out. And indeed, recent research suggests a direct connection between PMNs'
      influx and brain damage severity. This review highlights the latest research
      regarding the close interconnection between PMNs and co-working cells following
      cerebral ischemia. We describe how PMNs are attracted to the site of injury and
      their tasks within the inflamed brain tissue and the periphery. We further report
      of new findings regarding the interaction of PMNs with resident microglia,
      immigrating macrophages and T cells after stroke. Finally, we discuss recent
      research results from experimental studies in the context with current clinical
      trials and point out potential new therapeutic applications that could emerge
      from this new knowledge on the action and interaction of PMNs following cerebral
      ischemia.

PMID- 27884769
TI  - Upregulation of CD74 and its potential association with disease severity in
      subjects with ischemic stroke.
AB  - Macrophage migration inhibitory factor (MIF) is a key cytokine/chemokine in the
      activation and recruitment of inflammatory T lymphocytes known to exacerbate
      experimental stroke severity. MIF effects are mediated through its primary
      cellular receptor, CD74, the MHC class II invariant chain present on all class II
      expressing cells, including monocytes, macrophages and dendritic cells (DC). We
      demonstrated previously that partial MHC class II/peptide constructs (pMHC) can
      effectively treat mice with experimental stroke, in part through their ability to
      competitively inhibit MIF/CD74 interactions and downstream signaling. However,
      the role of MIF and CD74 in human ischemic stroke is not yet well established. To
      evaluate the therapeutic potential for pMHC, we assessed MIF and CD74 expression
      levels and their association with disease outcome in subjects with ischemic
      stroke. MIF levels were assessed in blood plasma by ELISA and CD74 expression was
      quantified by flow cytometry and qRT-PCR in peripheral blood mononuclear cells
      (PBMCs) obtained from subjects with ischemic stroke and age and sex-matched
      healthy controls (HC). MIF levels were increased in plasma and the number of
      CD74+ cells and CD74 mRNA expression levels were significantly increased in PBMC
      of subjects with ischemic stroke versus HC, mainly on CD4+ T cells, monocytes and
      DC. Greater increases of CD74+ cells were seen in subjects with cortical vs.
      subcortical infarcts and the number of CD74+ cells in blood correlated strongly
      with infarct size and neurological outcomes. However, differences in MIF and CD74
      expression were not affected by age, gender or lesion laterality. Increased CD74
      expression levels may serve as a useful biomarker for worse stroke severity and
      predicted outcomes in subjects with ischemic stroke and provide a rationale for
      potential future treatment with pMHC constructs.

PMID- 27884771
TI  - Rapid detection of Salmonella in raw chicken breast using real-time PCR combined
      with immunomagnetic separation and whole genome amplification.
AB  - We presented the first attempt to combine immunomagnetic separation (IMS), whole
      genome amplification by multiple displacement amplification (MDA) and real-time
      PCR for detecting a bacterial pathogen in a food sample. This method was
      effective in enabling real-time PCR detection of low levels of Salmonella
      enterica Serotype Enteritidis (SE) (~10 CFU/g) in raw chicken breast without
      culture enrichment. In addition, it was able to detect refrigeration-stressed SE
      cells at lower concentrations (~0.1 CFU/g) in raw chicken breast after a 4-h
      culture enrichment, shortening the detection process from days to hours and
      displaying no statistical difference in detection rate in comparison with a
      culture-based detection method. By substantially improving performance in SE
      detection over conventional real-time PCR, we demonstrated the potential of IMS
      MDA real-time PCR as a rapid, sensitive and affordable method for detecting
      Salmonella in food.

PMID- 27884772
TI  - Ovol2 gene inhibits the Epithelial-to-Mesenchymal Transition in lung
      adenocarcinoma by transcriptionally repressing Twist1.
AB  - BACKGROUND: Associated with recent achievements in therapy for advanced lung
      adenocarcinoma, there will still be an unmet medical need for effective treatment
      of stage IIIb/IV, and the prognosis of lung cancer is not optimistic till now.
      OBJECTIVE: In order to obtain some essential evidences for a potential targeted
      therapy in lung adenocarcinoma, the effects of Ovol2 gene on Epithelial-to
      Mesenchymal Transition (EMT) was observed and the probable mechanisms were
      analyzed. METHODS: Ovol2 expression was previously evaluated by immunochemistry
      in lung adenocarcinoma tissue, and Ovol2 was overexpressed by lentivirus
      infection in A549 cells. Subsequently, the migration and invasion ability of A549
      cells was tested by Transwell and Wound healing experiments. The mRNA level of
      genes correlated to EMT was detected by Real-time PCR, and the expression of
      reasonable makers was probed by Western Blot. Finally, rescue experiment,
      Luciferase assay, and chromatin immunoprecipitation assay were performed to
      explore the probable mechanisms. RESULTS: After treated with Ovol2
      overexpression, the expression level of E-cadherin was increased, while the
      expression level of Vimentin and Twist1 was declined not only in the mRNA level
      but also in the protein level. Moreover, we found that Ovol2 represses
      transcription of Twist1 by binding to its promoter directly. Wound healing and
      Transwell assays indicate that the migration and invasion ability were
      downregulated by Ovol2 in A549 cells. CONCLUSION: Ovol2 can suppress migration
      and invasion ability of A549 cells, and prevent EMT by inhibition of Twist1
      transcription directly.

PMID- 27884773
TI  - An intelligent prognostic system for analyzing patients with paraquat poisoning
      using arterial blood gas indexes.
AB  - The arterial blood gas (ABG) test is used to assess gas exchange in the lung, and
      the acid-base level in the blood. However, it is still unclear whether or not ABG
      test indexes correlate with paraquat (PQ) poisoning. This study investigates the
      predictive value of ABG tests in prognosing patients with PQ poisoning; it also
      identifies the most significant indexes of the ABG test. An intelligent machine
      learning-based system was established to effectively give prognostic analysis of
      patients with PQ poisoning based on ABG indexes. In the proposed system, an
      enhanced support vector machine combined with a feature selection strategy was
      developed to predict the risk status from a pool of 103 patients (56 males and 47
      females); of these, 52 subjects were deceased and 51 patients were alive. The
      proposed method was rigorously evaluated against the real-life dataset in terms
      of accuracy, sensitivity, and specificity. Additionally, the feature selection
      was investigated to identify correlating factors for the risk status. The results
      demonstrated that there were significant differences in ABG indexes between
      deceased and alive subjects (p-value <0.01). According to the feature selection,
      we found that the most important correlated indexes were associated with partial
      pressure of carbon dioxide (PCO2). This study discovered the relationship between
      ABG test and poisoning degree to provide a new avenue for prognosing PQ
      poisoning.

PMID- 27884774
TI  - Magnetically-responsive, multifunctional drug delivery nanoparticles for elastic
      matrix regenerative repair.
AB  - : Arresting or regressing growth of abdominal aortic aneurysms (AAAs), localized
      expansions of the abdominal aorta are contingent on inhibiting chronically
      overexpressed matrix metalloproteases (MMPs)-2 and -9 that disrupt elastic matrix
      within the aortic wall, concurrent with providing a stimulus to augmenting
      inherently poor auto-regeneration of these matrix structures. In a recent study
      we demonstrated that localized, controlled and sustained delivery of doxycycline
      (DOX; a tetracycline-based antibiotic) from poly(lactic-co-glycolic acid)
      nanoparticles (PLGA NPs), enhances elastic matrix deposition and MMP-inhibition
      at a fraction of the therapeutically effective oral dose. The surface
      functionalization of these NPs with cationic amphiphiles, which enhances their
      arterial uptake, was also shown to have pro-matrix regenerative and anti-MMP
      effects independent of the DOX. Based on the hypothesis that the incorporation of
      superparamagnetic iron oxide NPs (SPIONs) within these PLGA NPs would enhance
      their targetability to the AAA site under an applied external magnetic field, we
      sought to evaluate the functional effects of NPs co-encapsulating DOX and SPIONs
      (DOX-SPION NPs) on elastic matrix regeneration and MMP synthesis/activity in
      vitro within aneurysmal smooth muscle cell (EaRASMC) cultures. The DOX-SPION NPs
      were mobile under an applied external magnetic field, while enhancing elastic
      matrix deposition 1.5-2-fold and significantly inhibiting MMP-2 synthesis and MMP
      2 and -9 activities, compared to NP-untreated control cultures. These results
      illustrate that the multifunctional benefits of NPs are maintained following
      SPION co-incorporation. Additionally, preliminary studies carried out
      demonstrated enhanced targetability of SPION-loaded NPs within proteolytically
      disrupted porcine carotid arteries ex vivo, under the influence of an applied
      external magnetic field. Thus, this dual-agent loaded NP system proffers a
      potential non-surgical option for treating small growing AAAs, via controlled and
      sustained drug release from multifunctional, targetable nanocarriers. STATEMENT
      OF SIGNIFICANCE: Proactive screening of high risk elderly patients now enables
      early detection of abdominal aortic aneurysms (AAAs). There are no established
      drug-based therapeutic alternatives to surgery for AAAs, which is unsuitable for
      many elderly patients, and none which can achieve restore disrupted and lost
      elastic matrix in the AAA wall, which is essential to achieve growth arrest or
      regression. We have developed a first generation design of polymer nanoparticles
      (NPs) for AAA tissue localized delivery of doxycycline, a modified tetracycline
      drug at low micromolar doses at which it provides both pro-elastogenic and anti
      proteolytic benefits that can augment elastic matrix regenerative repair. The
      nanocarriers themselves are also uniquely chemically functionalized on their
      surface to also provide them pro-elastin-regenerative & anti-matrix degradative
      properties. To provide an active driving force for efficient uptake of intra
      lumenally infused NPs to the AAA wall, in this work, we have rendered our polymer
      NPs mobile in an applied magnetic field via co-incorporation of super
      paramagnetic iron oxide NPs. We demonstrate that such modifications significantly
      improve wall uptake of the NPs with no significant changes to their physical
      properties and regenerative benefits. Such NPs can potentially stimulate
      structural repair in the AAA wall following one time infusion to delay or prevent
      AAA growth to rupture. The therapy can provide a non-surgical treatment option
      for high risk AAA patients.

PMID- 27884776
TI  - Inverted orientation improves decellularization of whole porcine hearts.
AB  - : In structurally heterogeneous organs, such as heart, it is challenging to
      retain extracellular matrix integrity in the thinnest regions (eg, valves) during
      perfusion decellularization and completely remove cellular debris from thicker
      areas. The high inflow rates necessary to maintain physiologic pressure can
      distend or damage thin tissues, but lower pressures prolong the process and
      increase the likelihood of contamination. We examined two novel retrograde
      decellularization methods for porcine hearts: inverting the heart or venting the
      apex to decrease inflow rate. We measured flow dynamics through the aorta (Ao)
      and pulmonary artery (PA) at different Ao pressures and assessed the heart's
      appearance, turbidity of the outflow solutions, and coronary perfusion
      efficiency. We used rectangle image fitting of decellularized heart images to
      obtain a heart shape index. Using nonlinear optical microscopy, we determined the
      microstructure of collagen and elastin fibers of the aortic valve cusps. DNA,
      glycosaminoglycan, and residual detergent levels were compared. The inverted
      method was superior to the vented method, as shown by a higher coronary perfusion
      efficiency, more cell debris outflow, higher collagen and elastin content inside
      the aortic valve, lower DNA content, and better retention of the heart shape
      after decellularization. To our knowledge, this is the first study to use flow
      dynamics in a whole heart throughout the decellularization procedure to provide
      real-time information about the success of the process and the integrity of the
      vulnerable regions of the matrix. Heart orientation was important in optimizing
      decellularization efficiency and maintaining extracellular matrix integrity.
      STATEMENT OF SIGNIFICANCE: The use of decellularized tissue as a suitable
      scaffold for engineered tissue has emerged over the past decade as one of the
      most promising biofabrication platforms. The decellularization process removes
      all native cells, leaving the natural biopolymers, extracellular matrix materials
      and native architecture intact. This manuscript describes heart orientation as
      important in optimizing decellularization efficiency and maintaining
      extracellular matrix integrity. To our knowledge, this is the first study to
      assess flow dynamics in a whole heart throughout the decellularization procedure.
      Our findings compared to currently published methods demonstrate that continuous
      complex real-time measurements and analyses are required to produce an optimal
      scaffold for cardiac regeneration.

PMID- 27884775
TI  - Tuning acoustic and mechanical properties of materials for ultrasound phantoms
      and smart substrates for cell cultures.
AB  - : Materials with tailored acoustic properties are of great interest for both the
      development of tissue-mimicking phantoms for ultrasound tests and smart scaffolds
      for ultrasound mediated tissue engineering and regenerative medicine. In this
      study, we assessed the acoustic properties (speed of sound, acoustic impedance
      and attenuation coefficient) of three different materials (agarose,
      polyacrylamide and polydimethylsiloxane) at different concentrations or cross
      linking levels and doped with different concentrations of barium titanate ceramic
      nanoparticles. The selected materials, besides different mechanical features
      (stiffness from few kPa to 1.6MPa), showed a wide range of acoustic properties
      (speed of sound from 1022 to 1555m/s, acoustic impedance from 1.02 to 1.67MRayl
      and attenuation coefficient from 0.2 to 36.5dB/cm), corresponding to ranges in
      which natural soft tissues can fall. We demonstrated that this knowledge can be
      used to build tissue-mimicking phantoms for ultrasound-based medical procedures
      and that the mentioned measurements enable to stimulate cells with a highly
      controlled ultrasound dose, taking into account the attenuation due to the cell
      supporting scaffold. Finally, we were able to correlate for the first time the
      bioeffect on human fibroblasts, triggered by piezoelectric barium titanate
      nanoparticles activated by low-intensity pulsed ultrasound, with a precise
      ultrasound dose delivered. These results may open new avenues for the development
      of both tissue-mimicking materials for ultrasound phantoms and smart triggerable
      scaffolds for tissue engineering and regenerative medicine. STATEMENT OF
      SIGNIFICANCE: This study reports for the first time the results of a systematic
      acoustic characterization of agarose, polyacrylamide and polydimethylsiloxane at
      different concentrations and cross-linking extents and doped with different
      concentrations of barium titanate nanoparticles. These results can be used to
      build tissue-mimicking phantoms, useful for many ultrasound-based medical
      procedures, and to fabricate smart materials for stimulating cells with a highly
      controlled ultrasound dose. Thanks to this knowledge, we correlated for the first
      time a bioeffect (the proliferation increase) on human fibroblasts, triggered by
      piezoelectric nanoparticles, with a precise US dose delivered. These results may
      open new avenues for the development of both tissue-mimicking phantoms and smart
      triggerable scaffolds for tissue engineering and regenerative medicine.

PMID- 27884777
TI  - Anionic glycosylated polysulfone membranes for the affinity adsorption of low
      density lipoprotein via click reactions.
AB  - : An anionic glycosylated polysulfone (PSf) membrane was prepared as a high
      affinity adsorbent for low-density lipoprotein (LDL). The UV-induced grafting of
      acrylic acid to the membrane was followed by amidation and a 'thiol-yne' click
      reaction to achieve glycosylation and sulfonation. Membrane modification was
      confirmed by attenuated total reflectance-Fourier transform infrared spectroscopy
      and X-ray photoelectron spectroscopy. These tests revealed that the chemical
      compositions of the membranes' surfaces were easily regulated by controlling the
      'thiol-yne' click reaction through the feed ratio of 2,3,4,6-tetra-O-acetyl-1
      thio-beta-d-glucopyranose and sodium 3-mercapto-1-propanesulfonate. LDL
      adsorption and desorption rates were estimated using an enzyme-linked
      immunosorbent assay, which revealed that the obtained anionic glycosylated PSf
      membrane had a higher affinity for LDL than either glycosylated or sulfonated
      membranes alone. The combination of glycosyl and sulfonyl groups enhanced the
      membranes' affinities for LDL. The modified PSf membrane had an excellent
      biocompatibility and adsorbed a large amount of LDL, making it a promising
      material for LDL apheresis. STATEMENT OF SIGNIFICANCE: Low-density lipoprotein
      (LDL) adsorbents normally contain negative charged ligand to induce electrostatic
      interaction with the positively charged regions of LDL. Furthermore, saccharide
      is another common component which share in most of the LDL-adsorbents and the LDL
      receptor (LDLR). Such structural similarity impels us to investigate the
      synergistic effect of anionic and saccharide on LDL recognition. For this
      purpose, an anionic glycosylated membrane of which surface composition can be
      controlled by click reaction with mutable glycosyl/sulfonyl ratios was prepared.
      The obtained membrane showed better LDL adsorption/desorption property and the
      adsorption amount for LDL at an optimum feed ratio. This finding highlights the
      role of synergistic effect of anionic and saccharide, which offer a new strategy
      for designing LDL adsorbent with high efficiency.

PMID- 27884778
TI  - Expression of adipokines in osteoarthritis osteophytes and their effect on
      osteoblasts.
AB  - OBJECTIVE: Osteophyte formation in osteoarthritis (OA) is mediated by increased
      osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway.
      Obesity is regarded a risk factor in OA, yet little is known about the
      interaction between adipose tissue-derived factors, the adipokines, and bone
      formation, although adipokines are associated with the pathogenesis of OA.
      Therefore, the effect of adipokines on bone and cartilage forming cells and
      osteophyte development was analyzed. METHODS: Human OA osteophytes were
      histologically characterized and adipokine expression was evaluated by
      immunohistochemistry. Osteoblasts and chondrocytes were isolated from OA tissue
      and stimulated with adiponectin, resistin, or visfatin. Cytokine and
      osteoblast/chondrocyte markers were quantified and activation of Wnt and p38 MAPK
      signaling was analyzed. RESULTS: Adiponectin, resistin, and visfatin were
      expressed in OA osteophytes by various articular cell types. Stimulation of OA
      osteoblasts with adiponectin and of OA chondrocytes with visfatin led to an
      increased release of proinflammatory mediators but not to osteoblast
      differentiation or activation. Additionally, visfatin increased matrix degrading
      factors in chondrocytes. Wnt signaling was not altered by adipokines, but
      adiponectin induced p38 MAPK signaling in osteoblasts. CONCLUSION: Adipokines are
      present in OA osteophytes, and adiponectin and visfatin increase the release of
      proinflammatory mediators by osteoblasts and chondrocytes. The effects of
      adiponectin were mediated by p38 MAPK but not Wnt signaling in osteoblasts.
      Therefore, the results support the idea that adipokines do not directly influence
      osteophyte development but the proinflammatory conditions in OA.

PMID- 27884779
TI  - Gene-Targeted Next Generation Sequencing Identifies PNPLA1 Mutations in Patients
      with a Phenotypic Spectrum of Autosomal Recessive Congenital Ichthyosis: The
      Impact of Consanguinity.
AB  - Autosomal recessive congenital ichthyosis is a heterogeneous group of disorders
      associated with mutations in at least nine distinct genes. To ascertain the
      molecular basis of ichthyosis patients in Iran, a country of approximately 80
      million people with a high prevalence of customary consanguineous marriages, we
      have developed a gene-targeted next generation sequencing array consisting of 38
      genes reported in association with ichthyosis phenotypes. In a subset of nine
      extended consanguineous families, we found homozygous missense mutations in the
      PNPLA1 gene, six of them being distinct and, to our knowledge, previously
      unpublished. This gene encodes an enzyme with lipid hydrolase activity, important
      for development and maintenance of the barrier function of the epidermis. These
      six mutations, as well as four previously published mutations, reside exclusively
      within the patatin-like subdomain of PNPLA1 containing the catalytic site. The
      mutations clustered around the active center of the enzyme or resided at the
      surface of the protein possibly involved in the protein-protein interactions.
      Clinical features of the patients showed considerable intra- and interfamilial
      heterogeneity. Knowledge of the specific mutations allows identification of
      heterozygous carriers, assisting in genetic counseling, prenatal testing, and
      preimplantation genetic diagnosis in extended families at risk of recurrence of
      this disorder, the incidence of which is significantly increased in
      consanguineous marriages.

PMID- 27884781
TI  - Epigenetic mechanisms underlying lifespan and age-related effects of dietary
      restriction and the ketogenic diet.
AB  - Aging constitutes the central risk factor for major diseases including many forms
      of cancer, neurodegeneration, and cardiovascular diseases. The aging process is
      characterized by both global and tissue-specific changes in gene expression
      across taxonomically diverse species. While aging has historically been thought
      to entail cell-autonomous, even stochastic changes, recent evidence suggests that
      modulation of this process can be hierarchal, wherein manipulations of nutrient
      sensing neurons (e.g., in the hypothalamus) produce peripheral effects that may
      modulate the aging process itself. The most robust intervention extending
      lifespan, plausibly impinging on the aging process, involves different modalities
      of dietary restriction (DR). Lifespan extension by DR is associated with broad
      protection against diseases (natural and engineered). Here we review potential
      epigenetic processes that may link lifespan to age-related diseases, particularly
      in the context of DR and (other) ketogenic diets, focusing on brain and
      hypothalamic mechanisms.

PMID- 27884782
TI  - Is the plant-associated microbiota of Thymus spp. adapted to plant essential oil?
AB  - We examined whether the microbiota of two related aromatic thyme species, Thymus
      vulgaris and Thymus citriodorus, differs in relation to the composition of the
      respective essential oil (EO). A total of 576 bacterial isolates were obtained
      from three districts (leaves, roots and rhizospheric soil). They were
      taxonomically characterized and inspected for tolerance to the EO from the two
      thyme species. A district-related taxonomic pattern was found. In particular,
      high taxonomic diversity among the isolates from leaves was detected. Moreover,
      data obtained revealed a differential pattern of resistance of the isolates to
      EOs extracted from T. vulgaris and T. citriodorus, which was interpreted in terms
      of differing chemical composition of the EO of their respective host plants. In
      conclusion, we suggest that bacterial colonization of leaves in Thymus spp. is
      influenced by the EO present in leaf glandular tissue as one of the selective
      forces shaping endophytic community composition.

PMID- 27884783
TI  - Secondary multidrug efflux pump mutants alter Escherichia coli biofilm growth in
      the presence of cationic antimicrobial compounds.
AB  - Escherichia coli possesses many secondary active multidrug resistance
      transporters (MDTs) that confer overlapping substrate resistance to a broad range
      of antimicrobials via proton and/or sodium motive force. It is uncertain whether
      redundant MDTs uniquely alter cell survival when cultures grow planktonically or
      as biofilms. In this study, the planktonic and biofilm growth and antimicrobial
      resistance of 13 E. coli K-12 single MDT gene deletion strains in minimal and
      rich media were determined. Antimicrobial tolerance to tetracycline, tobramycin
      and benzalkonium were also compared for each DeltaMDT strain. Four E. coli MDT
      families were represented in this study: resistance nodulation and cell division
      members acrA, acrB, acrD, acrE, acrF and tolC; multidrug and toxin extruder mdtK;
      major facilitator superfamily emrA and emrB; and small multidrug resistance
      members emrE, sugE, mdtI and mdtJ. Deletions of multipartite efflux system genes
      acrB, acrE and tolC resulted in significant reductions in both planktonic and
      biofilm growth phenotypes and enhanced antimicrobial susceptibilities. The loss
      of remaining MDT genes produced similar or enhanced (acrD, acrE, emrA, emrB,
      mdtK, emrE and mdtJ) biofilm growth and antimicrobial resistance. DeltaMDT
      strains with enhanced antimicrobial tolerance also enhanced biofilm biomass.
      These findings suggest that many redundant MDTs regulate biofilm formation and
      drug tolerance.

PMID- 27884784
TI  - Phenotypic and genomic characterization of the antimicrobial producer
      Rheinheimera sp. EpRS3 isolated from the medicinal plant Echinacea purpurea:
      insights into its biotechnological relevance.
AB  - In recent years, there has been increasing interest in plant microbiota; however,
      despite medicinal plant relevance, very little is known about their highly
      complex endophytic communities. In this work, we report on the genomic and
      phenotypic characterization of the antimicrobial compound producer Rheinheimera
      sp. EpRS3, a bacterial strain isolated from the rhizospheric soil of the
      medicinal plant Echinacea purpurea. In particular, EpRS3 is able to inhibit
      growth of different bacterial pathogens (Bcc, Acinetobacter baumannii, and
      Klebsiella pneumoniae) which might be related to the presence of gene clusters
      involved in the biosynthesis of different types of secondary metabolites. The
      outcomes presented in this work highlight the fact that the strain possesses huge
      biotechnological potential; indeed, it also shows antimicrobial effects upon well
      described multidrug-resistant (MDR) human pathogens, and it affects plant root
      elongation and morphology, mimicking indole acetic acid (IAA) action.

PMID- 27884780
TI  - Regulation of metabolic health and aging by nutrient-sensitive signaling
      pathways.
AB  - All organisms need to be capable of adapting to changes in the availability and
      composition of nutrients. Over 75 years ago, researchers discovered that a
      calorie restricted (CR) diet could significantly extend the lifespan of rats, and
      since then a CR diet has been shown to increase lifespan and healthspan in model
      organisms ranging from yeast to non-human primates. In this review, we discuss
      the effects of a CR diet on metabolism and healthspan, and highlight emerging
      evidence that suggests that dietary composition - the precise macronutrients that
      compose the diet - may be just as important as caloric content. In particular, we
      discuss recent evidence that suggests protein quality may influence metabolic
      health. Finally, we discuss key metabolic pathways which may influence the
      response to CR diets and altered macronutrient composition. Understanding the
      molecular mechanisms responsible for the effects of CR and dietary composition on
      health and longevity may allow the design of novel therapeutic approaches to age
      related diseases.

PMID- 27884785
TI  - Viable but non-culturable state and toxin gene expression of enterohemorrhagic
      Escherichia coli O157 under cryopreservation.
AB  - As major food-borne pathogens worldwide, Escherichia coli are capable of toxin
      production directly causing severe human disease. However, routine methods are
      incapable of detecting viable but non-culturable (VBNC) bacteria in food products
      and raw materials, leading to false-negative identification. In this study, VBNC
      E. coli O157 strains were acquired after cryopreservation at -20  degrees C, with
      and without freeze-thawing; morphology was observed to be of shorter rod-shape,
      and toxin expression remained at relatively high levels. PMA-PCR assay for VBNC
      detection was also validated. Therefore, these results suggest that VBNC E. coli
      O157 strains may represent a strong threat to public health and food safety.

PMID- 27884786
TI  - Osteopontin and the dento-osseous pathobiology of X-linked hypophosphatemia.
AB  - Seven young patients with X-linked hypophosphatemia (XLH, having inactivating
      PHEX mutations) were discovered to accumulate osteopontin (OPN) at the sites of
      defective bone mineralization near osteocytes - the so-called hallmark
      periosteocytic (lacunar) "halos" of XLH. OPN was also localized in the
      pericanalicular matrix extending beyond the osteocyte lacunae, as well as in the
      hypomineralized matrix of tooth dentin. OPN, a potent inhibitor of mineralization
      normally degraded by PHEX, is a member of a family of acidic, phosphorylated,
      calcium-binding, extracellular matrix proteins known to regulate dental,
      skeletal, and pathologic mineralization. Associated with the increased amount of
      OPN (along with inhibitory OPN peptide fragments) in XLH bone matrix, we found an
      enlarged, hypomineralized, lacuno-canalicular network - a defective pattern of
      skeletal mineralization that decreases stiffness locally at: i) the cell-matrix
      interface in the pericellular environment of the mechanosensing osteocyte, and
      ii) the osteocyte's dendritic network of cell processes extending throughout the
      bone. Our findings of an excess of inhibitory OPN near osteocytes and their cell
      processes, and in dentin, spatially correlates with the defective mineralization
      observed at these sites in the skeleton and teeth of XLH patients. These changes
      likely contribute to the dento-osseous pathobiology of XLH, and participate in
      the aberrant bone adaptation and remodeling seen in XLH.

PMID- 27884788
TI  - The virtual dissecting room: Creating highly detailed anatomy models for
      educational purposes.
AB  - INTRODUCTION: Virtual 3D models are powerful tools for teaching anatomy. At the
      present day, there are a lot of different digital anatomy models, most of these
      commercial applications are based on a 3D model of a human body reconstructed
      from images with a 1mm intervals. The use of even smaller intervals may result in
      more details and more realistic appearances of 3D anatomy models. The aim of this
      study was to create a realistic and highly detailed 3D model of the hand and
      wrist based on small interval cross-sectional images, suitable for undergraduate
      and postgraduate teaching purposes with the possibility to perform a virtual
      dissection in an educational application. METHODS: In 115 transverse cross
      sections from a human hand and wrist, segmentation was done by manually
      delineating 90 different structures. With the use of Amira the segments were
      imported and a surface model/polygon model was created, followed by smoothening
      of the surfaces in Mudbox. In 3D Coat software the smoothed polygon models were
      automatically retopologied into a quadrilaterals formation and a UV map was
      added. In Mudbox, the textures from 90 structures were depicted in a realistic
      way by using photos from real tissue and afterwards height maps, gloss and
      specular maps were created to add more level of detail and realistic lightning on
      every structure. Unity was used to build a new software program that would
      support all the extra map features together with a preferred user interface.
      CONCLUSION: A 3D hand model has been created, containing 100 structures (90 at
      start and 10 extra structures added along the way). The model can be used
      interactively by changing the transparency, manipulating single or grouped
      structures and thereby simulating a virtual dissection. This model can be used
      for a variety of teaching purposes, ranging from undergraduate medical students
      to residents of hand surgery. Studying the hand and wrist anatomy using this
      model is cost-effective and not hampered by the limited access to real dissecting
      facilities.

PMID- 27884789
TI  - Surgery for advanced epithelial ovarian cancer.
AB  - Cytoreductive surgery for patients with advanced epithelial ovarian cancer has
      been practised since the pioneering work of Tom Griffiths in 1975. Further
      research has demonstrated the prognostic significance of the extent of metastatic
      disease pre-operatively, and of complete cytoreduction post-operatively. Patients
      with advanced epithelial ovarian cancer should be referred to high volume cancer
      units, and managed by multidisciplinary teams. The role of thoracoscopy and
      resection of intrathoracic disease is presently investigational. In recent years,
      there has been increasing use of neoadjuvant chemotherapy and interval
      cytoreductive surgery in patients with poor performance status, which is usually
      due to large volume ascites and/or large pleural effusions. Neoadjuvant
      chemotherapy reduces the post-operative morbidity, but if the tumour responds
      well to the chemotherapy, the inflammatory response makes the surgery more
      difficult. Post-operative morbidity is generally tolerable, but increases in
      older patients, and in those having multiple, aggressive surgical procedures,
      such as bowel resection or diaphragmatic stripping. Primary cytoreductive surgery
      should be regarded as the gold standard for most patients until a test is
      developed which would allow the prediction of platinum resistance pre
      operatively.

PMID- 27884790
TI  - Altered spermatogenesis, steroidogenesis and suppressed fertility in adult male
      rats exposed to genistein, a non-steroidal phytoestrogen during embryonic
      development.
AB  - This article focuses on the effects of prenatal exposure to genistein on the
      mother, her pregnancy and reproductive functions of the male progeny, since these
      issues have ethological relevance in both animals and humans. Pregnant Wistar
      rats received i.p. injections of genistein at a dose level of 2, 20 or 100 mg/kg
      body weight daily from 12th to 19th day of gestation. Male pups from control and
      genistein exposed animals were weaned and allowed to develop until 100 days of
      age; however, when they were 90 days old, twelve males from each group were
      cohabited with untreated 90-day old females for 8 days. Results revealed a
      significant decrease in indices of reproductive organs in adult male rats exposed
      to genistein during embryonic development. Dose dependent reduction was observed
      in daily sperm production and epididymal sperm density and quality in genistein
      treated rats. Significant decrease was observed in the activity levels of 3beta-
      and 17beta-hydroxysteroid dehydrogenases in testis of experimental rats with a
      decline in plasma testosterone levels. Histological examination of testis of
      genistein treated rats indicated deterioration in testicular architecture. In the
      fertility study, the mean number of implantations and live fetuses per dam mated
      with 100 mg genistein exposed males was reduced.

PMID- 27884787
TI  - Loss of Cbl-PI3K interaction modulates the periosteal response to fracture by
      enhancing osteogenic commitment and differentiation.
AB  - The periosteum contains multipotent skeletal progenitors that contribute to bone
      repair. The signaling pathways regulating the response of periosteal cells to
      fracture are largely unknown. Phosphatidylinositol-3 Kinase (PI3K), a prominent
      lipid kinase, is a major signaling protein downstream of several factors that
      regulate osteoblast differentiation. Cbl is an E3 ubiquitin ligase and a major
      adaptor protein that binds to the p85 regulatory subunit and modulates PI3K
      activity. Substitution of tyrosine 737 to phenylalanine (Y737F) in Cbl abolishes
      the interaction between Cbl and p85 subunit without affecting the Cbl's ubiquitin
      ligase function. Here, we investigated the role of PI3K signaling during the very
      early stages of fracture healing using OsterixRFP reporter mice. We found that
      the absence of PI3K regulation by Cbl resulted in robust periosteal thickening,
      with increased proliferation of periosteal cells. While the multipotent
      properties of periosteal progenitors to differentiate into chondrocytes and
      adipocytes did not change, osteogenic differentiation in the absence of Cbl-PI3K
      interaction was highly augmented. The increased stability and nuclear
      localization of Osterix observed in periosteal cells lacking Cbl-PI3K interaction
      may explain this enhanced osteogenic differentiation since the expression of
      Osterix transcriptional target genes including osteocalcin and BSP are increased
      in YF cells. Overall, our findings highlight a hitherto unexplored and novel role
      for Cbl and PI3K in modulating the osteogenic response of periosteal cells during
      the early stages of fracture repair.

PMID- 27884791
TI  - Immunomodulatory effect of characterized extract of Zataria multiflora on Th1,
      Th2 and Th17 in normal and Th2 polarization state.
AB  - The effect of the extract of Zataria multiflora (Z. multiflora) on IFN-gamma,
      FOXP3, IL-4, TGF-beta, and IL-17 gene expression was evaluated in cultured
      splenocytes obtained from control, nontreated asthma or sensitized mice (group
      S), Sensetized animals treated with dexamethasone or three concentrations of Z.
      multiflora extract (200, 400 and 800 MUg/ml) (n = 6, for each group). IFN-gamma
      and FOXP3 gene expressions were significantly decreased (P < 0.001 for both
      cases) but IL-4 (P < 0.001) and IL-17 (P < 0.05) were increased in group S
      compared to control group. Z. Multiflora extract 800 MUg/ml, significantly
      upregulated IFN-gamma gene expression (P < 0.01) and its 400 and 800 MUg/ml
      concentrations increased FOXP3 gene expression (P < 0.05 and P < 0.001,
      respectively) compared to group S. Z. multiflora extract at all concentrations
      (200, 400 and 800 MUg/ml) decreased TGF-beta gene expression and its lowest
      concentration significantly reduced IL-17 gene expression compared to group S (P
      < 0.001 for all cases). Only IL-4 and TGF-beta gene expression was significantly
      decreased following treatment with dexamethasone (P < 0.001 for both cases). The
      results indicated an increase in IFN-gamma and FOXP3 but decrease in TGF-beta and
      IL-17 gene expression profile in sensitized splenocytes treated with the extract,
      which might be partially due to the presence of one of its constituent,
      carvacrol.

PMID- 27884792
TI  - RIFM fragrance ingredient safety assessment, beta-Guaiene, CAS Registry Number 88
      84-6.

PMID- 27884793
TI  - Sex, stress and sleep apnoea: Decreased susceptibility to upper airway muscle
      dysfunction following intermittent hypoxia in females.
AB  - Obstructive sleep apnoea syndrome (OSAS) is a devastating respiratory control
      disorder more common in men than women. The reasons for the sex difference in
      prevalence are multifactorial, but are partly attributable to protective effects
      of oestrogen. Indeed, OSAS prevalence increases in post-menopausal women. OSAS is
      characterized by repeated occlusions of the pharyngeal airway during sleep.
      Dysfunction of the upper airway muscles controlling airway calibre and
      collapsibility is implicated in the pathophysiology of OSAS, and sex differences
      in the neuro-mechanical control of upper airway patency are described. It is
      widely recognized that chronic intermittent hypoxia (CIH), a cardinal feature of
      OSAS due to recurrent apnoea, drives many of the morbid consequences
      characteristic of the disorder. In rodents, exposure to CIH-related redox stress
      causes upper airway muscle weakness and fatigue, associated with mitochondrial
      dysfunction. Of interest, in adults, there is female resilience to CIH-induced
      muscle dysfunction. Conversely, exposure to CIH in early life, results in upper
      airway muscle weakness equivalent between the two sexes at 3 and 6 weeks of age.
      Ovariectomy exacerbates the deleterious effects of exposure to CIH in adult
      female upper airway muscle, an effect partially restored by oestrogen replacement
      therapy. Intriguingly, female advantage intrinsic to upper airway muscle exists
      with evidence of substantially greater loss of performance in male muscle during
      acute exposure to severe hypoxic stress. Sex differences in upper airway muscle
      physiology may have relevance to human OSAS. The oestrogen-oestrogen receptor
      alpha axis represents a potential therapeutic target in OSAS, particularly in
      post-menopausal women.

PMID- 27884794
TI  - Peroxiredoxin 6 suppresses Muc5ac overproduction in LPS-induced airway
      inflammation through H2O2-EGFR-MAPK signaling pathway.
AB  - Mucus hypersecretion is a prominent mechanism in airway inflammation. Muc5ac is a
      major component of mucus and can be activated by reactive oxygen species (ROS).
      Peroxiredoxin 6 (Prdx6) highly expresses in airway epithelium and protects the
      airway from oxidative stress. In this study, we investigated the roles of Prdx6
      in lipopolysaccharide (LPS)-induced mucin production in mice. We found that the
      levels of H2O2 and the Muc5ac mRNA were significantly increased in Prdx6 (-/-)
      mice compared to those in C57BL/6J mice after LPS instillation, which were
      markedly inhibited by epithelial growth factor receptor (EGFR) inhibitor
      Elrotinib. In vitro studies showed that mRNA levels of Prdx6 were decreased while
      H2O2 and Muc5ac were increased in a dose-dependent manner after LPS exposure,
      with significant increase in Prdx6 knockdown bronchial epithelial cells compared
      with those in normal epithelial cells. LPS-induced Muc5ac release was
      significantly inhibited by EGFR inhibitor, p38 inhibitor and JNK inhibitor, but
      not ERK1/2 inhibitor, indicating that the H2O2-EGFR-MAPK pathway is likely
      involved in the responses. This study indicated that Prdx6 decreased LPS-induced
      Muc5ac increase and played important roles in mucin hypersecretion after LPS
      exposure.

PMID- 27884795
TI  - Forced oscillation technique as a predictor of FEV1 improvement in asthma.
AB  - The usefulness of the forced oscillation technique (FOT) for predicting the
      treatment outcomes in untreated asthmatic patients is unknown. We investigated
      whether FOT could predict an improvement in FEV1 following treatment. FOT,
      spirometry, and fractional exhaled nitric oxide were performed in 31 outpatients
      before and after undergoing a minimum of two months combination therapy of
      inhaled corticosteroids and long-acting beta2-agonists. The patients were
      classified as responders or nonresponders to treatment based on the presence or
      absence of a 10% improvement in the FEV1. The responders to the treatment regimen
      exhibited lower FEV1, FEV1/FVC, FEF25-75%, and higher respiratory resistance at
      5Hz (R5), as well as a difference between R5 and R20 (R5-R20) at baseline
      compared to the nonresponders. In the multivariate logistic regression analyses,
      a change in FEV1 greater than 10% was independently predicted by the R5 (adjusted
      odds ratio: 15.9). The ROC curve analyses revealed that the area under the curve
      for R5 (0.731) was larger than that of the other parameters. Thus, R5 is a forced
      oscillatory parameter and predicts an improvement in FEV1 following treatment.

PMID- 27884796
TI  - Can the measurement of pulmonary diffusing capacity for nitric oxide replace the
      measurement of pulmonary diffusing capacity for carbon monoxide?
AB  - Pulmonary diffusing capacity for carbon monoxide (DLCO) has been an important
      pulmonary function test used since the 1950's. It measures the uptake of CO from
      the alveolar space into pulmonary capillary blood, following the same path as
      oxygen. It's used to evaluate/follow the progress of various lung diseases. In
      the eighties, a new test was developed similar to the DLCO test: pulmonary
      diffusing capacity for nitric oxide (DLNO). About 81-90% of the variance in DLNO
      is shared by DLCO in patients with cardiopulmonary disease and in healthy
      subjects. When DLNO is abnormally low, so is DLCO, and when DLNO is normal, so is
      DLCO (Kappa Statistic=0.69, n=251). The probability that DLNO and DLCO will be
      abnormally low when a cardiopulmonary disease is present (sensitivity) is 79% and
      68%, respectively. The DLNO test avoids many technical issues associated with the
      measurement of DLCO: (1) DLNO is relatively unaffected by inspired oxygen
      concentration or ambient pressure, (2) DLNO is unaffected by carboxyhemoglobin,
      (3) DLNO is minimally affected by hemoglobin (Hb) concentration, thus correcting
      for Hb is not needed. (4) DLNO is more affected by lung volume compared to DLCO,
      thus DLNO divided by alveolar volume (KNO) is a better measure than KCO in those
      with restrictive lung disease, and (5) DLNO is a more stable measure over time
      compared to DLCO. Therefore, DLNO has several advantages over DLCO in the
      management of patients and could replace the DLCO test in most cases moving
      forward.

PMID- 27884798
TI  - Neural markers of loss aversion in resting-state brain activity.
AB  - Neural responses in striatal, limbic and somatosensory brain regions track
      individual differences in loss aversion, i.e. the higher sensitivity to potential
      losses compared with equivalent gains in decision-making under risk. The
      engagement of structures involved in the processing of aversive stimuli and
      experiences raises a further question, i.e. whether the tendency to avoid losses
      rather than acquire gains represents a transient fearful overreaction elicited by
      choice-related information, or rather a stable component of one's own preference
      function, reflecting a specific pattern of neural activity. We tested the latter
      hypothesis by assessing in 57 healthy human subjects whether the relationship
      between behavioral and neural loss aversion holds at rest, i.e. when the BOLD
      signal is collected during 5minutes of cross-fixation in the absence of an
      explicit task. Within the resting-state networks highlighted by a spatial group
      Independent Component Analysis (gICA), we found a significant correlation between
      strength of activity and behavioral loss aversion in the left ventral striatum
      and right posterior insula/supramarginal gyrus, i.e. the very same regions
      displaying a pattern of neural loss aversion during explicit choices. Cross-study
      analyses confirmed that this correlation holds when voxels identified by gICA are
      used as regions of interest in task-related activity and vice versa. These
      results suggest that the individual degree of (neural) loss aversion represents a
      stable dimension of decision-making, which reflects in specific metrics of
      intrinsic brain activity at rest possibly modulating cortical excitability at
      choice.

PMID- 27884799
TI  - The infectious hypoxia: occurrence and causes during Shigella infection.
AB  - Hypoxia is defined as a tissue oxygenation status below physiological needs.
      During Shigella infection, an infectious hypoxia is induced within foci of
      infection. In this review, we discuss how Shigella physiology and virulence are
      modulated and how the main recruited immune cells, the neutrophils, adapt to this
      environment.

PMID- 27884800
TI  - The Hidden Cost of Medicine.

PMID- 27884797
TI  - Breathing abnormalities in animal models of Rett syndrome a female neurogenetic
      disorder.
AB  - A characteristic feature of Rett syndrome (RTT) is abnormal breathing accompanied
      by several other neurological and cognitive disorders. Since RTT rodent models
      became available, studies have begun shedding insight into the breathing
      abnormalities at behavioral, cellular and molecular levels. Defects are found in
      several groups of brainstem neurons involved in respiratory control, and
      potential neural mechanisms have been suggested. The findings in animal models
      are helpful in therapeutic strategies for people with RTT with respect to
      lowering sudden and unexpected death, preventing secondary developmental
      consequences, and improving the quality of lives.

PMID- 27884801
TI  - Effect of Flexible Duty Hour Policies on Length of Stay for Complex Intra
      Abdominal Operations: A Flexibility in Duty Hour Requirements for Surgical
      Trainees (FIRST) Trial Analysis.
AB  - BACKGROUND: Changes to resident duty hour policies in the Flexibility in Duty
      Hour Requirements for Surgical Trainees (FIRST) trial could impact hospitalized
      patients' length of stay (LOS) by altering care coordination. Length of stay can
      also serve as a reflection of all complications, particularly those not captured
      in the FIRST trial (eg pneumothorax from central line). Programs were randomized
      to either maintaining current ACGME duty hour policies (Standard arm) or more
      flexible policies waiving rules on maximum shift lengths and time off between
      shifts (Flexible arm). Our objective was to determine whether flexibility in
      resident duty hours affected LOS in patients undergoing high-risk surgical
      operations. STUDY DESIGN: Patients were identified who underwent hepatectomy,
      pancreatectomy, laparoscopic colectomy, open colectomy, or ventral hernia repair
      (2014-2015 academic year) at 154 hospitals participating in the FIRST trial. Two
      procedure-stratified evaluations of LOS were undertaken: multivariable negative
      binomial regression analysis on LOS and a multivariable logistic regression
      analysis on the likelihood of a prolonged LOS (>75th percentile). RESULTS: Before
      any adjustments, there was no statistically significant difference in overall
      mean LOS between study arms (Flexible Policy: mean [SD] LOS 6.03 [5.78] days vs
      Standard Policy: mean LOS 6.21 [5.82] days; p = 0.74). In adjusted analyses,
      there was no statistically significant difference in LOS between study arms
      overall (incidence rate ratio for Flexible vs Standard: 0.982; 95% CI, 0.939
      1.026; p = 0.41) or for any individual procedures. In addition, there was no
      statistically significant difference in the proportion of patients with prolonged
      LOS between study arms overall (Flexible vs Standard: odds ratio = 1.028; 95% CI,
      0.871-1.212) or for any individual procedures. CONCLUSIONS: Duty hour flexibility
      had no statistically significant effect on LOS in patients undergoing complex
      intra-abdominal operations.

PMID- 27884802
TI  - Association Between Flexible Duty Hour Policies and General Surgery Resident
      Examination Performance: A Flexibility in Duty Hour Requirements for Surgical
      Trainees (FIRST) Trial Analysis.
AB  - BACKGROUND: Concerns persist about the effect of current duty hour reforms on
      resident educational outcomes. We investigated whether a flexible, less
      restrictive duty hour policy (Flexible Policy) was associated with differential
      general surgery examination performance compared with current ACGME duty hour
      policy (Standard Policy). STUDY DESIGN: We obtained examination scores on the
      American Board of Surgery In-Training Examination, Qualifying Examination
      (written boards), and Certifying Examination (oral boards) for residents in 117
      general surgery residency programs that participated in the Flexibility in Duty
      Hour Requirements for Surgical Trainees (FIRST) Trial. Using bivariate analyses
      and regression models, we compared resident examination performance across study
      arms (Flexible Policy vs Standard Policy) for 2015 and 2016, and 1 year of the
      Qualifying Examination and Certifying Examination. Adjusted analyses accounted
      for program-level factors, including the stratification variable for
      randomization. RESULTS: In 2016, FIRST trial participants were 4,363 general
      surgery residents. Mean American Board of Surgery In-Training Examination scores
      for residents were not significantly different between study groups (Flexible
      Policy vs Standard Policy) overall (Flexible Policy: mean [SD] 502.6 [100.9] vs
      Standard Policy: 502.7 [98.6]; p = 0.98) or for any individual postgraduate year
      level. There was no difference in pass rates between study arms for either the
      Qualifying Examination (Flexible Policy: 90.4% vs Standard Policy: 90.5%; p =
      0.99) or Certifying Examination (Flexible Policy: 86.3% vs Standard Policy:
      88.6%; p = 0.24). Results from adjusted analyses were consistent with these
      findings. CONCLUSIONS: Flexible, less-restrictive duty hour policies were not
      associated with differences in general surgery resident performance on
      examinations during the FIRST Trial. However, more years under flexible duty hour
      policies might be needed to observe an effect.

PMID- 27884803
TI  - Association Between Resident Perceptions of Patient Safety and Duty Hour
      Violations.
AB  - BACKGROUND: Residents are often required to balance whether to adhere to duty
      hour policies or violate them to care for patients and obtain educational
      experiences. Little is known about why residents violate duty hour policies and
      whether there is a relationship between how often residents violate duty hours
      and concerns about patient safety. Our objective was to assess the association
      between resident duty hour violations and resident concerns about patient safety.
      STUDY DESIGN: We analyzed survey data collected from surgery residents who
      completed the 2015 American Board of Surgery In-Training Examination, excluding
      those in the Flexible Policy arm of the Flexibility in Duty Hour Requirements for
      Surgical Trainees (FIRST) trial. Perceptions of how duty hour restrictions affect
      patient safety were dichotomized as either "positive/neutral" or "negative."
      Resident duty hour violations in a typical month were separated as "frequently"
      (>=3 times) or "infrequently" (<3 times). Rates were compared and regression
      models were used to examine the association between negative perceptions and duty
      hour violations, adjusting for resident and program-level covariates. RESULTS:
      Overall, 25.3% of trainees under current policies perceived that current ACGME
      duty hour policies negatively affected patient safety. This negative perception
      increased with PGY level (PGY1: 18.5%, PGY2 to 3: 22.6%, PGY4 to 5: 32.0%; p <
      0.001). Residents with negative perceptions more often reported frequent duty
      violations (positive/neutral: 20.0% vs negative: 32.7%; p < 0.001). After
      adjustment for covariates, a negative perception of how duty hour policies affect
      patient safety was significantly associated with a higher likelihood of frequent
      duty hour violations among all trainees grouped together (odds ratio [OR] = 1.89;
      95% CI, 1.60-2.22), and separately for interns (OR = 2.59; 95% CI, 1.70-3.93),
      junior (OR = 1.62; 95% CI 1.22-2.16), and senior residents (OR = 1.99; 95% CI,
      1.54-2.58). CONCLUSIONS: Trainees who reported perceiving negative effects of
      duty hour policies on patient safety were more likely to report frequent duty
      hour violations.

PMID- 27884804
TI  - Gender-Based Differences in Surgical Residents' Perceptions of Patient Safety,
      Continuity of Care, and Well-Being: An Analysis from the Flexibility in Duty Hour
      Requirements for Surgical Trainees (FIRST) Trial.
AB  - BACKGROUND: Little is known about gender differences in residency training
      experiences and whether duty hour policies affect these differences. Using data
      from the Flexibility in Duty Hour Requirements for Surgical Trainees (FIRST)
      trial, we examined gender differences in surgical resident perceptions of patient
      safety, education, health and well-being, and job satisfaction, and assessed
      whether duty hour policies affected gender differences. STUDY DESIGN: We compared
      proportions of male and female residents expressing dissatisfaction or perceiving
      a negative effect of duty hours on aspects of residency training (ie patient
      safety, resident education, well-being, job satisfaction) overall and by PGY.
      Logistic regression models with robust clustered SEs were used to test for
      significant gender differences and interaction effects of duty hour policies on
      gender differences. RESULTS: Female PGY2 to 3 residents were more likely than
      males to be dissatisfied with patient safety (odds ratio [OR] = 2.50; 95% CI,
      1.29-4.84) and to perceive a negative effect of duty hours on most health and
      well-being outcomes (OR = 1.51-2.10; all p < 0.05). Female PGY4 to 5 residents
      were more likely to be dissatisfied with resident education (OR = 1.56; 95% CI,
      1.03-2.35) and time for rest (OR = 1.55; 95% CI, 1.05-2.28) than males. Flexible
      duty hours reduced gender differences in career dissatisfaction among interns (p
      = 0.028), but widened gender differences in negative perceptions of duty hours on
      patient safety (p < 0.001), most health and well-being outcomes (p < 0.05), and
      outcomes related to job satisfaction (p < 0.05) among PGY2 to 3 residents.
      CONCLUSIONS: Gender differences exist in perceptions of surgical residency. These
      differences vary across cohorts and can be influenced by duty hour policies.

PMID- 27884805
TI  - Use and Underlying Reasons for Duty Hour Flexibility in the Flexibility in Duty
      Hour Requirements for Surgical Trainees (FIRST) Trial.
AB  - BACKGROUND: The Flexibility in Duty Hour Requirements for Surgical Trainees
      (FIRST) Trial randomly assigned surgical residency programs to either standard
      duty hour policies or flexible policies that eliminated caps on shift lengths and
      time off between shifts. Our objectives were to assess adherence to duty hour
      requirements in the Standard Policy arm and examine how often and why duty hour
      flexibility was used in the Flexible Policy arm. STUDY DESIGN: A total of 3,795
      residents in the FIRST trial completed a survey in January 2016 (response rate
      >95%) that asked how often and why they exceeded current standard duty hour
      limits in both study arms. RESULTS: Flexible Policy interns worked more than 16
      hours continuously at least once in a month more frequently than Standard Policy
      residents (86% vs 37.8%). Flexible Policy residents worked more than 28 hours
      once in a month more frequently than Standard Policy residents (PGY1: 64% vs
      2.9%; PGY2 to 3: 62.4% vs 41.9%; PGY4 to 5: 52.2% vs 36.6%), but this occurred
      most frequently only 1 to 2 times per month. Although residents reported working
      more than 80 hours in a week 3 or more times in the most recent month more
      frequently under Flexible Policy vs Standard Policy (19.9% vs 16.2%), the
      difference was driven by interns (30.9% vs 19.6%), and there were no significant
      differences in exceeding 80 hours among PGY2 to 5 residents. The most common
      reasons reported for extending duty hours were facilitating care transitions
      (76.6%), stabilizing critically ill patients (70.7%), performing routine
      responsibilities (67.9%), and operating on patients known to the trainee (62.0%).
      CONCLUSIONS: There were differences in duty hours worked by residents in the
      Flexible vs Standard Policy arms of the FIRST trial, but it appeared that
      residents generally used the flexibility for patient care and educational
      opportunities selectively.

PMID- 27884806
TI  - Exploring Qualitative Perspectives on Surgical Resident Training, Well-Being, and
      Patient Care.
AB  - BACKGROUND: The Flexibility in Duty Hour Requirements for Surgical Trainees
      (FIRST) trial found no difference in patient outcomes or resident well-being
      between more restrictive and flexible duty hour policies. Qualitative methods are
      appropriate for better understanding the experience and perceptions of those
      affected by duty hour regulations. We conducted a pilot qualitative study on how
      resident duty hour regulations are perceived by general surgery program
      directors, surgical residents, and attending surgeons who participated in the
      FIRST Trial. STUDY DESIGN: Semi-structured qualitative interviews were pilot
      tested with program directors, residents, and attendings to examine initial
      perceptions of the standard and flexible policies implemented during the trial.
      The transcribed interviews were analyzed thematically using a constant
      comparative approach and grouped first by study arm and then by level (patient,
      surgeon, program, and national). RESULTS: More restrictive duty hours were
      perceived as creating a tension between resident personal and professional well
      being. Standard Policy resulted in more transitions, which was perceived as
      creating vulnerable gaps in patient care. Standard Policy restrictions were seen
      as particularly challenging for interns and often led to inadequate preparation
      for promotion and encouraged a shift mentality. CONCLUSIONS: In our pilot study,
      interviewees valued the flexibility afforded in the Flexible Policy arm, as it
      allowed them to maximize patient safety and educational attainment. Additional
      qualitative research will expand on program director, resident, and attending
      perceptions of resident duty hours as well as perceptions of patient safety.
      Qualitative methods can contribute to the national debate on resident duty hours.

PMID- 27884807
TI  - Helix-helix interactions in membrane domains of bitopic proteins: Specificity and
      role of lipid environment.
AB  - Interaction between transmembrane helices often determines biological activity of
      membrane proteins. Bitopic proteins, a broad subclass of membrane proteins, form
      dimers containing two membrane-spanning helices. Some aspects of their structure
      function relationship cannot be fully understood without considering the protein
      lipid interaction, which can determine the protein conformational ensemble.
      Experimental and computer modeling data concerning transmembrane parts of bitopic
      proteins are reviewed in the present paper. They highlight the importance of
      lipid-protein interactions and resolve certain paradoxes in the behavior of such
      proteins. Besides, some properties of membrane organization provided a clue to
      understanding of allosteric interactions between distant parts of proteins.
      Interactions of these kinds appear to underlie a signaling mechanism, which could
      be widely employed in the functioning of many membrane proteins. Treatment of
      membrane proteins as parts of integrated fine-tuned proteolipid system promises
      new insights into biological function mechanisms and approaches to drug design.
      This article is part of a Special Issue entitled: Lipid order/lipid defects and
      lipid-control of protein activity edited by Dirk Schneider.

PMID- 27884808
TI  - Biodegradable nano-polymers as delivery vehicles for therapeutic small non-coding
      ribonucleic acids.
AB  - Nowadays, small non-coding Ribo Nucleic Acids (sncRNAs) such as siRNA, miRNA and
      shRNA are extremely serving to gene regulation. They are involved in many
      biological processes and in an increasing number of studies regarding a variety
      of application of sncRNAs toward human health and relieving diseases ranging from
      metabolic disorders to those involving various organ systems as well as different
      types of cancer. One of the most severe limitations for applying RNA interference
      technology is the absence of safe and effective carriers for in vivo delivery,
      including localizing the molecules to a specific site of interest and sustaining
      the presentation of the payloads for a controlled period of time. In this review,
      we focus on the sncRNA functions and recent advances on the delivery of these
      molecules by biodegradable, biocompatible and nontoxic biopolymers including
      chitosan, cyclodextrins, poly-l-lysine, dextran, poly (lactic co-glycolic acid),
      polyglutamic acid, hyaluronic acid and gelatin.

PMID- 27884809
TI  - Construction of a Streptococcus agalactiae phoB mutant and evaluation of its
      potential as an attenuated modified live vaccine in golden pompano, Trachinotus
      ovatus.
AB  - Streptococcus agalactiae is a Gram-positive pathogen that can survive inside
      professional phagocytes and nonphagocytic cells to cause septicemia and
      meningoencephalitis in freshwater and marine fish. However, vaccines based on
      extracellular products (ECP) and formalin-killed whole S. agalactiae cells, as
      well as subunit vaccine are unable to protect fish from infection by variant
      serotypes S. agalactiae. The search for live attenuated vaccine with highly
      conserved and virulent-related genes is essential for producing a vaccine to help
      understand and control streptococcosis In this study, the phoB gene was cloned
      from pathogenic S. agalactiae TOS01 strain and the mutant strain SADeltaphoB was
      constructed via allelic exchange mutagenesis. The results showed that the deduced
      amino acid of S. agalactiae TOS01 shares high similarities with other
      Streptococcus spp. and has high conserved response regulator receiver domain
      (REC) and DNA-binding effector domain of two-component system response regulators
      (Trans_reg_C). Cell adherence and invasion assays, challenge experiments and
      histopathological changes post-vaccination were performed and observed, the
      results showed that the mutant strain SADeltaphoB has a lower adherence and
      invasion rate and less virulent than the wild type strain in golden pompano, and
      it doesn't induce clinical symptoms and obvious pathological changes in golden
      pompano, thereby indicating that the deletion of phoB affects the virulence and
      infectious capacity of S. agalactiae. Golden pompano vaccinated via
      intraperitoneal injection SADeltaphoB had the relative percent survival value of
      93.1% after challenge with TOS01, demonstrating its high potential as an
      effective attenuated live vaccine candidate. Real-time PCR assays showed that the
      SADeltaphoB was able to enhance the expression of immune-related genes, including
      MHC-I, MyD88, IL-22 and IL-10 after vaccination, indicating that the SADeltaphoB
      is able to induce humoral and cell-mediated immune response in golden pompano
      over a long period of time.

PMID- 27884810
TI  - Mobile Apps in Oncology: A Survey on Health Care Professionals' Attitude Toward
      Telemedicine, mHealth, and Oncological Apps.
AB  - BACKGROUND: Mobile apps are an evolving trend in the medical field. To date, few
      apps in an oncological context exist. OBJECTIVE: The aim was to analyze the
      attitude of health care professionals (HCPs) toward telemedicine, mHealth, and
      mobile apps in the field of oncology. METHODS: We developed and conducted an
      online survey with 24 questions evaluating HCPs' general attitude toward
      telemedicine and patients using medical mobile apps. Specific questions on the
      possible functionality for patients and the resulting advantages and
      disadvantages for both the patients' and HCPs' daily clinical routine were
      evaluated. RESULTS: A total of 108 HCPs completed the survey. In all, 88.9%
      (96/108) considered telemedicine useful and 84.3% (91/108) supported the idea of
      an oncological app complementing classical treatment. Automatic reminders,
      timetables, and assessment of side effects and quality of life during therapy
      were rated as the most important functions. In contrast, uncertainty regarding
      medical responsibility and data privacy were reasons mostly named by critics.
      Most (64.8%, 70/108) were in favor of an alert function due to data input needing
      further clarification, and 94% (66/70) were willing to contact the patient after
      a critical alert. In all, 93.5% (101/108) supported the idea of using the
      collected data for scientific research. Moreover, 75.0% (81/108) believed
      establishing a mobile app could be beneficial for the providing hospital.
      CONCLUSIONS: A majority of HCPs are in favor of telemedicine and the use of
      oncological apps by patients. Assessing side effects can lead to quicker response
      and thus lower inconvenience for patients. Clinical data, such as life quality
      and treatment satisfaction, could be used to evaluate and improve the therapy
      workflow. Eventually, a mobile app would enhance the patients' relationship to
      their treating department because they are in permanent contact.

PMID- 27884811
TI  - How Professionals Share an E-Care Plan for the Elderly in Primary Care:
      Evaluating the Use of an E-Communication Tool by Different Combinations of
      Professionals.
AB  - BACKGROUND: Home-dwelling elderly patients with multimorbidity are at risk of
      fragmentation of care because of the many different professionals involved and a
      potentially unclear level of communication. Multidisciplinary communication seems
      to occur incidentally. Mutual feedback is needed for a professional team to
      provide consistent care and adequate support to the patient system. eHealth
      technology can improve outcomes. OBJECTIVE: The aim of this study was to evaluate
      the use of a tool, Congredi, for electronic communication by professionals for
      the care of home-dwelling elderly patients. METHODS: The research group was
      recruited through general practices and home care organizations. Congredi, a tool
      designed for multidisciplinary communication, was made available for
      professionals in primary care. It consists of a care plan and a communication
      channel (secure emailing). Professionals opened Congredi records for elderly
      patients who had 2 or more professionals involved. The records were the unit of
      analysis. Data were gathered from the Congredi system over a period of 42 weeks.
      RESULTS: An inclusion rate of 21.4% (203/950) was achieved; nearly half of the
      participants were nurses. During the study, professionals were active in 448
      patient records; female professionals were prevalent. In the patient records, 3
      types of actions (care activities, emailing, and process activities) were
      registered. Most activities occurred in the multidisciplinary records (mean
      12.2), which had twice the number of activities of monodisciplinary records
      (6.35), and solo records had a mean of 3.43 activities. Most activities were care
      activities (mean 9.14), emailing had a mean of 0.89 activities, and process
      activities had a mean of 0.29. CONCLUSIONS: An e-communication tool (Congredi)
      was usable for improving multidisciplinary communication among professionals. It
      even seemed to yield results for 40% of the professionals who used the e-care
      plan on their own. The content of the tool provided an active communication
      practice, with significant increases observed in the actions that must be shared
      for the effective coordination of care.

PMID- 27884812
TI  - Consumers' Use of UMLS Concepts on Social Media: Diabetes-Related Textual Data
      Analysis in Blog and Social Q&A Sites.
AB  - BACKGROUND: The widely known terminology gap between health professionals and
      health consumers hinders effective information seeking for consumers. OBJECTIVE:
      The aim of this study was to better understand consumers' usage of medical
      concepts by evaluating the coverage of concepts and semantic types of the Unified
      Medical Language System (UMLS) on diabetes-related postings in 2 types of social
      media: blogs and social question and answer (Q&A). METHODS: We collected 2 types
      of social media data: (1) a total of 3711 blogs tagged with "diabetes" on Tumblr
      posted between February and October 2015; and (2) a total of 58,422 questions and
      associated answers posted between 2009 and 2014 in the diabetes category of
      Yahoo! Answers. We analyzed the datasets using a widely adopted biomedical text
      processing framework Apache cTAKES and its extension YTEX. First, we applied the
      named entity recognition (NER) method implemented in YTEX to identify UMLS
      concepts in the datasets. We then analyzed the coverage and the popularity of
      concepts in the UMLS source vocabularies across the 2 datasets (ie, blogs and
      social Q&A). Further, we conducted a concept-level comparative coverage analysis
      between SNOMED Clinical Terms (SNOMED CT) and Open-Access Collaborative Consumer
      Health Vocabulary (OAC CHV)-the top 2 UMLS source vocabularies that have the most
      coverage on our datasets. We also analyzed the UMLS semantic types that were
      frequently observed in our datasets. RESULTS: We identified 2415 UMLS concepts
      from blog postings, 6452 UMLS concepts from social Q&A questions, and 10,378 UMLS
      concepts from the answers. The medical concepts identified in the blogs can be
      covered by 56 source vocabularies in the UMLS, while those in questions and
      answers can be covered by 58 source vocabularies. SNOMED CT was the dominant
      vocabulary in terms of coverage across all the datasets, ranging from 84.9% to
      95.9%. It was followed by OAC CHV (between 73.5% and 80.0%) and Metathesaurus
      Names (MTH) (between 55.7% and 73.5%). All of the social media datasets shared
      frequent semantic types such as "Amino Acid, Peptide, or Protein," "Body Part,
      Organ, or Organ Component," and "Disease or Syndrome." CONCLUSIONS: Although the
      3 social media datasets vary greatly in size, they exhibited similar conceptual
      coverage among UMLS source vocabularies and the identified concepts showed
      similar semantic type distributions. As such, concepts that are both frequently
      used by consumers and also found in professional vocabularies such as SNOMED CT
      can be suggested to OAC CHV to improve its coverage.

PMID- 27884814
TI  - Shadow of the law in cases of avoidable harm.

PMID- 27884813
TI  - Development and Feasibility Testing of PROMPT-Care, an eHealth System for
      Collection and Use of Patient-Reported Outcome Measures for Personalized
      Treatment and Care: A Study Protocol.
AB  - BACKGROUND: Patient-reported outcome (PRO) measures have been used widely to
      screen for depression, anxiety, and symptoms in cancer patients. Computer-based
      applications that collect patients' responses and transfer them to the treating
      health professional in real time have the potential to improve patient well-being
      and cancer outcomes. OBJECTIVE: This study will test the feasibility and
      acceptability of a newly developed eHealth system which facilitates PRO data
      capture from cancer patients, data linkage and retrieval to support clinical
      decisions and patient self-management, and data retrieval to support ongoing
      evaluation and innovative research. METHODS: The eHealth system is being
      developed in consultation with 3 overarching content-specific expert advisory
      groups convened for this project: the clinical advisory group, technical advisory
      group, and evaluation advisory group. The following work has already been
      completed during this phase of the study: the Patient-Reported Outcome Measures
      for Personalized Treatment and Care (PROMPT-Care) eHealth system was developed,
      patient-reported outcomes were selected (distress, symptoms, unmet needs),
      algorithms to inform intervention thresholds for clinical and self-management
      were determined, clinician PRO feedback summary and longitudinal reports were
      designed, and patient self-management resources were collated. PROsaiq, a custom
      information technology system, will transfer PRO data in real time into the
      hospital-based oncology information system to support clinical decision making.
      The PROMPT-Care system feasibility and acceptability will be assessed through
      patients completing PROMPT-Care assessments, participating in face-to-face
      cognitive interviews, and completing evaluation surveys and telephone interviews
      and oncology staff participating in telephone interviews. RESULTS: Over the
      course of 3 months, the system will be pilot-tested with up to 50 patients
      receiving treatment or follow-up care and 6 oncology staff at 2 hospitals in New
      South Wales, Australia. Data will be collected to determine the accuracy and
      completeness of data transfer procedures, extent of missing data from
      participants' assessments, acceptability of the eHealth system and usefulness of
      the self-management resources (via patient evaluation surveys and interviews),
      and acceptability and perceived usefulness of real-time PRO reporting (via
      oncology staff interviews) at the completion of the pilot phase. CONCLUSIONS:
      This research investigates implementation of evidence into real world clinical
      practice through development of an efficient and user-friendly eHealth system.
      This study of feasibility and acceptability of the newly developed eHealth system
      will inform the next stage of larger scale testing and future implementation of
      the system as part of routine care. CLINICALTRIAL: Australian New Zealand
      Clinical Trials Registry ACTRN1261500135294;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369299&isReview=
      rue (Archived by WebCite at http://www.webcitation.org/6lzylG5A0).

PMID- 27884815
TI  - David Oliver: Keeping older doctors in the job.

PMID- 27884817
TI  - Promise of new Alzheimer's drug is dashed after lack of evidence.

PMID- 27884818
TI  - Doctors should nap during night shifts, conference hears.

PMID- 27884819
TI  - Government must be clearer in its claims about NHS funding, says statistics
      watchdog.

PMID- 27884820
TI  - Una destinatio, viae diversae: Does exposure to the vaginal microbiota confer
      health benefits to the infant, and does lack of exposure confer disease risk?

PMID- 27884821
TI  - The effect of different durations of remission on damage accrual: results from a
      prospective monocentric cohort of Caucasian patients.
AB  - AIM: To identify the shortest duration of remission associated with improved
      outcomes in systemic lupus erythematosus (SLE). METHODS: We studied 293 Caucasian
      patients with SLE during 7-year follow-up. Disease activity was assessed by SLE
      Disease Activity Index 2000 and damage by Systemic Lupus International
      Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We
      defined three remission levels: complete, clinical off-corticosteroids, clinical
      on-corticosteroids (prednisone 1-5 mg/day). The effect of different durations of
      remission (1, 2, 3, 4 and >=5 consecutive years) on damage was evaluated by
      multivariate logistic regression analysis. RESULTS: Among patients achieving 1
      year (27 patients), 2-year (47 patients), 3-year (45 patients), 4-year (26
      patients) remission, damage was similar irrespective of the level of remission
      achieved, whereas, among patients achieving >=5-year remission (113 patients),
      damage was higher in those in clinical remission on-corticosteroids (p<0.001).In
      multivariate analysis, >=2 consecutive year remission was protective against
      damage (OR (95% CI)): 2 years 0.228 (0.061 to 0.850); 3 years 0.116 (0.031 to
      0.436); 4 years 0.118 (0.027 to 0.519) and >=5 years 0.044 (0.012 to 0.159).
      Predictors of damage were cumulative prednisone dose >=180 mg/month (3.136 (1.276
      to 7.707)), antiphospholipid antibody syndrome (5.517 (2.092 to 14.546)),
      vasculitis (3.107 (1.030 to 9.307)) and number of flare/year (8.769 (1.692 to
      45.449)). CONCLUSIONS: Two consecutive years is the shortest duration of
      remission associated with a decrease in damage progression in Caucasian patients
      with SLE.

PMID- 27884823
TI  - Researcher suing PubPeer was found culpable of misconduct, court documents show.

PMID- 27884825
TI  - Statins for primary prevention of cardiovascular disease.

PMID- 27884827
TI  - Brazilian health authorities on alert after rise in deaths from chikungunya.

PMID- 27884828
TI  - Effects of age on left atrial volume and strain parameters using echocardiography
      in a normal black population.
AB  - OBJECTIVE: Normal cut-off values for left atrial (LA) size and function may be
      altered by aging and ethnic differences. No age-related reference values for LA
      volumetric measurements or LA strain exist in Africans. We aimed to establish
      normal age-appropriate values of LA size and function in black Africans.
      Additionally, we studied the correlation between age, LA strain and volumetric
      parameters. METHODS: In this prospective, cross-sectional study of 120
      individuals (mean age 38.7 +/- 12.8 years, 50% men), subjects were classified
      into four age groups: 18-29, 30-39, 40-49 and 50-70 years. LA volumes were
      measured by biplane Simpson's method, and Philips QLAB 9 (Amsterdam, The
      Netherlands) speckle-tracking software was used to measure LA peak strain in the
      reservoir (ER) and contractile phase (ECT). RESULTS: No significant differences
      in the maximum and minimum LAVi were noted among the four age categories (P =
      0.1, P = 0.2). LA volumetric function assessment showed no difference in
      reservoir function between age groups (P > 0.05), conduit function decreased with
      advancing age (r = -0.3, P < 0.001) and booster function displayed a significant
      increase with age (LA active emptying volume index, P = 0.001). There was a
      significant decrease in LA ER (P < 0.0001) in the older age groups, whereas ECT
      remained unchanged (P = 0.27). CONCLUSION: Age-related changes in LA reservoir,
      conduit and contractile function in black Africans are similar to those observed
      in other populations, as was the trend of declining ER with advancing age. The
      preservation of ECT with increasing age requires further analysis.

PMID- 27884822
TI  - A framework for remission in SLE: consensus findings from a large international
      task force on definitions of remission in SLE (DORIS).
AB  - OBJECTIVES: Treat-to-target recommendations have identified 'remission' as a
      target in systemic lupus erythematosus (SLE), but recognise that there is no
      universally accepted definition for this. Therefore, we initiated a process to
      achieve consensus on potential definitions for remission in SLE. METHODS: An
      international task force of 60 specialists and patient representatives
      participated in preparatory exercises, a face-to-face meeting and follow-up
      electronic voting. The level for agreement was set at 90%. RESULTS: The task
      force agreed on eight key statements regarding remission in SLE and three
      principles to guide the further development of remission definitions:1.
      Definitions of remission will be worded as follows: remission in SLE is a durable
      state characterised by ...................... (reference to symptoms, signs,
      routine labs).2. For defining remission, a validated index must be used, for
      example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0,
      British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European
      consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments
      included, and supplemented with physician's global assessment.3. Distinction is
      made between remission off and on therapy: remission off therapy requires the
      patient to be on no other treatment for SLE than maintenance antimalarials; and
      remission on therapy allows patients to be on stable maintenance antimalarials,
      low-dose corticosteroids (prednisone <=5 mg/day), maintenance immunosuppressives
      and/or maintenance biologics.The task force also agreed that the most appropriate
      outcomes (dependent variables) for testing the prognostic value (construct
      validity) of potential remission definitions are: death, damage, flares and
      measures of health-related quality of life. CONCLUSIONS: The work of this
      international task force provides a framework for testing different definitions
      of remission against long-term outcomes.

PMID- 27884829
TI  - Patient care is at risk from lack of new funds in autumn statement, healthcare
      leaders warn.

PMID- 27884830
TI  - Burgess AW, Wilson EMA, Metcalf D. Stimulation by human placental conditioned
      medium of hemopoietic colony formation by human marrow cells. Blood.
      1977;49(4):573-583.

PMID- 27884831
TI  - Is the lymphoma better? Not easy to determine.

PMID- 27884832
TI  - Novel antivirals for HCV-associated lymphomas.

PMID- 27884833
TI  - Pericytes: new EPO-producing cells in the brain.

PMID- 27884834
TI  - Glycans of plasma ADAMTS13.

PMID- 27884835
TI  - Sickle cell disease: the price of cure.

PMID- 27884836
TI  - Pseudo Chediak-Higashi anomaly in acute monoblastic leukemia.

PMID- 27884837
TI  - Characteristic peripheral blood smear findings in disorders of cobalamin
      metabolism.

PMID- 27884838
TI  - Gill S, Tasian SK, Ruella M, et al. Preclinical targeting of human acute myeloid
      leukemia and myeloablation using chimeric antigen receptor-modified T cells.
      Blood. 2014;123(15):2343-2354.

PMID- 27884839
TI  - Morillo-Gutierrez B, Beier R, Rao K, et al. Treosulfan-based conditioning for
      allogeneic HSCT in children with chronic granulomatous disease: a multicenter
      experience. Blood. 2016;128(3):440-448.

PMID- 27884840
TI  - Long-term effects of the Active for Life Year 5 (AFLY5) school-based cluster
      randomised controlled trial.
AB  - OBJECTIVE: To investigate the long-term effectiveness of a school-based
      intervention to improve physical activity and diet in children. DESIGN: Cluster
      randomised controlled trial. SETTING: 60 primary schools in the southwest of
      England. PARTICIPANTS: Primary school children who were aged 8-9 years at
      recruitment, 9-10 years during the intervention and 10-11 years at the long-term
      follow-up assessment. INTERVENTION: Teacher training, provision of lesson and
      child-parent interactive homework plans and teaching materials. MAIN OUTCOME
      MEASURES: Primary outcomes were accelerometer-assessed minutes of moderate to
      vigorous physical activity (MVPA) per day, accelerometer-assessed minutes of
      sedentary behaviour per day and reported daily consumption of servings of fruit
      and vegetables. RESULTS: 60 schools with 2221 eligible children were recruited.
      As in the previously published assessment immediately after the end of the
      intervention, none of the three primary outcomes differed between children in
      schools allocated to the intervention, compared with those in control schools at
      the end of the long-term follow-up (1 year after the end of the intervention).
      Differences in secondary outcomes were consistent with those at the immediate
      follow-up, with no evidence that these had diminished over time. Comparing
      intervention with control schools, the difference in mean child-reported screen
      viewing at the weekend was -16.03 min (95% CI -32.82 to 0.73), for servings of
      snacks per day, the difference was -0.11 (95% CI -0.39 to 0.06), in servings of
      high-energy drinks per day -0.20 (95% CI -0.39 to -0.01) and in servings of high
      fat foods per day -0.12 (95% CI -0.39 to 0.00). None of these reached our
      predefined level of statistical significance, especially after accounting for
      multiple testing. CONCLUSIONS: School-based curriculum interventions alone are
      unlikely to have a major public health impact on children's diet and physical
      activity. TRIAL REGISTRATION NUMBER: ISRCTN50133740, Post-results.

PMID- 27884842
TI  - Predictors of in-hospital mortality among patients with pulmonary tuberculosis: a
      protocol of systematic review and meta-analysis of observational studies.
AB  - INTRODUCTION: Tuberculosis (TB) continues to be a major public health issue
      worldwide, with 1.4 million deaths occurring annually. There is uncertainty
      regarding which factors are associated with in-hospital mortality among patients
      with pulmonary TB. This knowledge gap complicates efforts to identify and improve
      the management of those individuals with TB at greatest risk of death. The aim of
      this systematic review and meta-analysis is to establish predictors of in
      hospital mortality among patients with pulmonary TB to enhance the evidence base
      for public policy. METHODS AND ANALYSIS: Studies will be identified by a MEDLINE,
      EMBASE and Global Health search. Eligible studies will be cohort and case-control
      studies that report predictors or risk factors for in-hospital mortality among
      patients with pulmonary TB and an adjusted analysis to explore factors associated
      with in-hospital mortality. We will use the Grading of Recommendations
      Assessment, Development and Evaluation approach to summarise the findings of some
      reported predictors. Teams of 2 reviewers will screen the titles and abstracts of
      all citations identified in our search, independently and in duplicate, extract
      data, and assess scientific quality using standardised forms quality assessment
      and tools tailored. We will pool all factors that were assessed for an
      association with mortality that were reported by >1 study, and presented the OR
      and the associated 95% CI. When studies provided the measure of association as a
      relative risk (RR), we will convert the RR to OR using the formula provided by
      Wang. For binary data, we will calculate a pooled OR, with an associated 95% CI.
      ETHICS AND DISSEMINATION: This study is based on published data, and therefore
      ethical approval is not a requirement. Findings will be disseminated through
      publication in peer-reviewed journals and conference presentations at relevant
      conferences. TRIAL REGISTRATION NUMBER: CRD42015025755.

PMID- 27884841
TI  - Herbal medicines for the treatment of otitis media with effusion: a systematic
      review of randomised controlled trials.
AB  - OBJECTIVES: This systematic review aimed to assess the clinical evidence
      supporting the use of herbal medicines (HMs) for the treatment of otitis media
      with effusion (OME). DESIGN: Systematic review and meta-analysis. DATA SOURCES:
      MEDLINE, EMBASE, Cochrane Library, AMED, CINAHL and three trial registries were
      searched up to January 2015. We also searched five Korean medical databases
      (KoreaMed, RISS, OASIS, DBPIA and KISS) and three Chinese databases (CNKI,
      Wanfang and VIP). STUDY ELIGIBILITY CRITERIA: This study included randomised
      clinical trials that reported the effects of HM for OME. The primary outcome was
      the complete resolution of OME at 2 or 3 months post randomisation. Secondary
      outcomes included the partial or complete resolution at all possible time points
      and hearing test. Three authors independently screened the titles and abstracts,
      selected studies and extracted the data relating to trial quality,
      characteristics and results. RESULTS: A total of 2141 potentially relevant
      studies were identified, of which 17 randomised clinical trials met our inclusion
      criteria. Most were evaluated as having a high or unclear risk of bias. Tongqiao
      tablets, Tongqiao huoxue decoctions and Tsumura-Saireito were associated with a
      lower complete or partial resolution rate when compared with conventional
      medicines (CMs) (p=0.02, p=0.0001, and p=0.04, respectively), and similar
      outcomes were observed with Huanglong tonger pills, Erzhang decoctions and
      Shenling baizhu powder when combined with CM versus CM alone (p<0.00001, p=0.02,
      and p=0.05, respectively). Tongqiao huoxue decoction plus CM appeared to be more
      effective than CM in terms of improving the pure tone threshold levels
      (p=0.0007). Tsumura-Saireito was found to affect the proportion of patients with
      normalised tympanometry (p=0.03). CONCLUSIONS: Despite some indications of
      potential symptom improvement, the evidence regarding the effectiveness and
      efficacy of HMs for OME is of poor quality and therefore inconclusive. PROTOCOL
      REGISTRATION NUMBER: CRD42013005430.

PMID- 27884843
TI  - Traumatic brain injury in England and Wales: prospective audit of epidemiology,
      complications and standardised mortality.
AB  - OBJECTIVES: To provide a comprehensive assessment of the management of traumatic
      brain injury (TBI) relating to epidemiology, complications and standardised
      mortality across specialist units. DESIGN: The Trauma Audit and Research Network
      collects data prospectively on patients suffering trauma across England and
      Wales. We analysed all data collected on patients with TBI between April 2014 and
      June 2015. SETTING: Data were collected on patients presenting to emergency
      departments across 187 hospitals including 26 with specialist neurosurgical
      services, incorporating factors previously identified in the Ps14 multivariate
      logistic regression (Ps14n) model multivariate TBI outcome prediction model. The
      frequency and timing of secondary transfer to neurosurgical centres was assessed.
      RESULTS: We identified 15 820 patients with TBI presenting to neurosurgical
      centres directly (6258), transferred from a district hospital to a neurosurgical
      centre (3682) and remaining in a district general hospital (5880). The commonest
      mechanisms of injury were falls in the elderly and road traffic collisions in the
      young, which were more likely to present in coma. In severe TBI (Glasgow Coma
      Score (GCS) <=8), the median time from admission to imaging with CT scan is 0.5
      hours. Median time to craniotomy from admission is 2.6 hours and median time to
      intracranial pressure monitoring is 3 hours. The most frequently documented
      complication of severe TBI is bronchopneumonia in 5% of patients. Risk-adjusted W
      scores derived from the Ps14n model indicate that no neurosurgical unit fell
      outside the 3 SD limits on a funnel plot. CONCLUSIONS: We provide the first
      comprehensive report of the management of TBI in England and Wales, including
      data from all neurosurgical units. These data provide transparency and suggests
      equity of access to high-quality TBI management provided in England and Wales.

PMID- 27884844
TI  - Medication reconciliation as a medication safety initiative in Ethiopia: a study
      protocol.
AB  - INTRODUCTION: Medication related adverse events are common, particularly during
      transitions of care, and have a significant impact on patient outcomes and
      healthcare costs. Medication reconciliation (MedRec) is an important initiative
      to achieve the Quality Use of Medicines, and has been adopted as a standard
      practice in many developed countries. However, the impact of this strategy is
      rarely described in Ethiopia. The aims of this study are to explore patient
      safety culture, and to develop, implement and evaluate a theory informed MedRec
      intervention, with the aim of minimising the incidence of medication errors
      during hospital admission. METHODS AND ANALYSES: The study will be conducted in a
      resource limited setting. There are three phases to this project. The first phase
      is a mixed methods study of healthcare professionals' perspectives of patient
      safety culture and patients' experiences of medication related adverse events. In
      this phase, the Hospital Survey on Patient Safety Culture will be used along with
      semi-structured indepth interviews to investigate patient safety culture and
      experiences of medication related adverse events. The second phase will use a
      semi-structured interview guide, designed according to the 12 domains of the
      Theoretical Domains Framework, to explore the barriers and facilitators to
      medication safety activities delivered by hospital pharmacists. The third phase
      will be a single centre, before and after study, that will evaluate the impact of
      pharmacist conducted admission MedRec in an emergency department (ED). The main
      outcome measure is the incidence and potential clinical severity of medication
      errors. We will then analyse the differences in the incidence and severity of
      medication errors before and after initiation of an ED pharmacy service.

PMID- 27884846
TI  - Real-world evidence studies into treatment adherence, thresholds for intervention
      and disparities in treatment in people with type 2 diabetes in the UK.
AB  - PURPOSE: The University of Surrey-Lilly Real World Evidence (RWE) diabetes cohort
      has been established to provide insights into the management of type 2 diabetes
      mellitus (T2DM). There are 3 areas of study due to be conducted to provide
      insights into T2DM management: exploration of medication adherence, thresholds
      for changing diabetes therapies, and ethnicity-related or socioeconomic-related
      disparities in management. This paper describes the identification of a cohort of
      people with T2DM which will be used for these analyses, through a case finding
      algorithm, and describes the characteristics of the identified cohort.
      PARTICIPANTS: A cohort of people with T2DM was identified from the Royal College
      of General Practitioners Research and Surveillance Centre (RCGP RSC) data set.
      This data set comprises electronic patient records collected from a nationally
      distributed sample of 130 primary care practices across England with scope to
      increase the number of practices to 200. FINDINGS TO DATE: A cohort (N=58 717) of
      adults with T2DM was identified from the RCGP RSC population (N=1 260 761), a
      crude prevalence of diabetes of 5.8% in the adult population. High data quality
      within the practice network and an ontological approach to classification
      resulted in a high level of data completeness in the T2DM cohort; ethnicity
      identification (82.1%), smoking status (99.3%), alcohol use (93.3%), glycated
      haemoglobin (HbA1c; 97.9%), body mass index (98.0%), blood pressure (99.4%),
      cholesterol (87.4%) and renal function (97.8%). Data completeness compares
      favourably to other, similarly large, observational cohorts. The cohort comprises
      a distribution of ages, socioeconomic and ethnic backgrounds, diabetes
      complications, and comorbidities, enabling the planned analyses. FUTURE PLANS:
      Regular data uploads from the RCGP RSC practice network will enable this cohort
      to be followed prospectively. We will investigate medication adherence, explore
      thresholds and triggers for changing diabetes therapies, and investigate any
      ethnicity-related or socioeconomic-related disparities in diabetes management.

PMID- 27884845
TI  - Prevalence and determinants of carotid plaque in the cross-sectional REFINE
      Reykjavik study.
AB  - OBJECTIVE: Carotid plaque and intima-media thickness are non-invasive arterial
      markers that are used as surrogate end points for cardiovascular disease. The aim
      was to assess the prevalence and severity of carotid plaque, and examine its
      determinant risk factors and their association to the common carotid artery
      intima-media thickness (CCA-IMT) in a general population. METHODS: We examined
      6524 participants aged 25-69 years in the population-based REFINE (Risk
      Evaluation For INfarct Estimates)-Reykjavik study. Plaques at the bifurcation and
      internal carotid arteries were evaluated. Mean CCA-IMT was measured in the near
      and far walls of the common carotid arteries. RESULTS: The prevalence of minimal,
      moderate and severe plaque was 35.0%, 8.9% and 1.1%, respectively, and the mean
      CCA-IMT was 0.73 (SD 0.14) mm. Age, sex, smoking and type 2 diabetes mellitus
      (T2DM) were the strongest risk factors associated with plaque, followed by
      systolic blood pressure, total cholesterol, body mass index and family history of
      myocardial infarct. Low educational level was also strongly and independently
      associated with plaque. CCA-IMT shared the same risk factors except for a non
      significant association with T2DM and family history of myocardial infarction
      (MI). Participants with T2DM had greater plaque prevalence, 2-fold higher in
      those <50 years and 17-30% greater in age groups 50-54 to 60-64, and more
      significant plaques (moderate or severe) were the difference in prevalence was
      24% in age group 50-54 and >=60% in older age groups, compared with non-T2DM.
      CONCLUSIONS: Carotid plaque and CCA-IMT have mostly common determinants. However,
      T2DM and family history of MI were associated with plaque but not with CCA-IMT.
      Greater prevalence and more severe plaques in individuals with T2DM raise the
      concern that with increasing prevalence of T2DM we may expect an increase in
      atherosclerosis and its consequences.

PMID- 27884847
TI  - Long-term mortality in mothers with perinatal losses and risk modification by
      surviving children and attained education: a population-based cohort study.
AB  - OBJECTIVE: To assess the association between perinatal losses and mother's long
      term mortality and modification by surviving children and attained education.
      DESIGN: A population-based cohort study. SETTING: Norwegian national registries.
      PARTICIPANTS: We followed 652 320 mothers with a first delivery from 1967 and
      completed reproduction before 2003, until 2010 or death. We excluded mothers with
      plural pregnancies, without information on education (0.3%) and women born
      outside Norway. MAIN OUTCOME MEASURES: Main outcome measures were age-specific
      (40-69 years) cardiovascular and non-cardiovascular mortality. We calculated
      mortality in mothers with perinatal losses, compared with mothers without, and in
      mothers with one loss by number of surviving children in strata of mothers'
      attained education (<11 years (low), >=11 years (high)). RESULTS: Mothers with
      perinatal losses had increased crude mortality compared with mothers without;
      total: HR 1.3 (95% CI 1.3 to 1.4), cardiovascular: HR 1.8 (1.5 to 2.1), non
      cardiovascular: HR 1.3 (1.2 to 1.4). Childless mothers with one perinatal loss
      had increased mortality compared with mothers with one child and no loss;
      cardiovascular: low education HR 2.7 (1.7 to 4.3), high education HR 0.91 (0.13
      to 6.5); non-cardiovascular: low education HR 1.6 (1.3 to 2.2), high education HR
      1.8 (1.1 to 2.9). Mothers with one perinatal loss, surviving children and high
      education had no increased mortality, whereas corresponding mothers with low
      education had increased mortality; cardiovascular: two surviving children HR 1.7
      (1.2 to 2.4), three or more surviving children HR 1.6 (1.1 to 2.4); non
      cardiovascular: one surviving child HR 1.2 (1.0 to 1.5), two surviving children
      HR 1.2 (1.1 to 1.4). CONCLUSIONS: Irrespective of education, we find excess
      mortality in childless mothers with a perinatal loss. Increased mortality in
      mothers with one perinatal loss and surviving children was limited to mothers
      with low education.

PMID- 27884849
TI  - ACCESS HD pilot: A randomised feasibility trial Comparing Catheters with fistulas
      in Elderly patientS Starting haemodialysis.
AB  - INTRODUCTION: The selection of the type of vascular access for haemodialysis is
      an important intervention question. However, only observational studies are
      available to inform decision-making in this area, and they are at high risk of
      selection bias. While a clinical trial comparing the effects of the 2 most
      frequently chosen strategies for haemodialysis access (fistulas and catheters) on
      patient important and 'hard' clinical end points is needed, the feasibility of
      such a trial is uncertain. METHODS AND ANALYSIS: This open-label pilot randomised
      controlled trial will test the feasibility and safety of randomising elderly
      people (>=65 years) who start haemodialysis with a central venous catheter (the
      most common initial type of haemodialysis access), and are eligible to receive a
      fistula, to a catheter-based strategy (comparator) or to a fistula-based strategy
      (intervention). We will enrol 100 patients at 10 centres across Canada.
      Participants assigned to the catheter-strategy arm will continue to use
      catheters; participants assigned to the fistula-strategy arm will receive a
      surgical attempt at fistula creation. The inclusion criteria are designed to
      minimise the risk of protocol violation and attrition. The primary outcome is
      feasibility, which we will assess by measuring: (1) the proportion of
      participants deemed eligible for the trial who consent to randomisation; and (2)
      the proportion of participants randomised to the intervention who receive the
      fistula surgery within 90 days of randomisation. Secondary outcomes will include
      safety outcomes, the reasons people and healthcare providers may not accept
      randomisation, and the reasons sites may not adhere to the trial protocol. ETHICS
      AND DISSEMINATION: The Conjoint Health Research Ethics Board at the University of
      Calgary approved the study protocol. We will submit the results of this
      feasibility study in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:
      NCT02675569, Pre-results.

PMID- 27884848
TI  - Are differences in travel time or distance to healthcare for adults in global
      north countries associated with an impact on health outcomes? A systematic
      review.
AB  - OBJECTIVES: To investigate whether there is an association between differences in
      travel time/travel distance to healthcare services and patients' health outcomes
      and assimilate the methodologies used to measure this. DESIGN: Systematic Review.
      We searched MEDLINE, Embase, Web of Science, Transport database, HMIC and EBM
      Reviews for studies up to 7 September 2016. Studies were excluded that included
      children (including maternity), emergency medical travel or countries classed as
      being in the global south. SETTINGS: A wide range of settings within primary and
      secondary care (these were not restricted in the search). RESULTS: 108 studies
      met the inclusion criteria. The results were mixed. 77% of the included studies
      identified evidence of a distance decay association, whereby patients living
      further away from healthcare facilities they needed to attend had worse health
      outcomes (eg, survival rates, length of stay in hospital and non-attendance at
      follow-up) than those who lived closer. 6 of the studies identified the reverse
      (a distance bias effect) whereby patients living at a greater distance had better
      health outcomes. The remaining 19 studies found no relationship. There was a
      large variation in the data available to the studies on the patients'
      geographical locations and the healthcare facilities attended, and the methods
      used to calculate travel times and distances were not consistent across studies.
      CONCLUSIONS: The review observed that a relationship between travelling further
      and having worse health outcomes cannot be ruled out and should be considered
      within the healthcare services location debate.

PMID- 27884850
TI  - Comparative effectiveness and safety of oral anticoagulants for atrial
      fibrillation in real-world practice: a population-based cohort study protocol.
AB  - INTRODUCTION: Anticoagulants are arguably the most important drug family of all,
      based on the frequency and duration of their use, and the clinical importance and
      frequency of benefits and harms. Several direct acting oral anticoagulants
      (DOACs) have recently joined warfarin for the treatment of atrial fibrillation,
      with a resultant significant expansion in use of oral anticoagulants (OACs). Our
      objectives are to compare safety and effectiveness of DOACs versus warfarin in a
      full population where anticoagulation management is good and to identify which
      types of patients do better with DOACs versus warfarin and vice versa. METHODS
      AND ANALYSIS: This is a retrospective cohort study of all adults living in
      British Columbia who have a diagnosis of atrial fibrillation in hospital or
      medical service data, and a first prescription for an OAC. Coprimary outcomes are
      ischaemic stroke and systemic embolism (benefit) and major bleeding (harm).
      Secondary outcomes include net clinical benefit (composite of stroke, systemic
      embolism, major bleeds, myocardial infarction, pulmonary embolism and death),
      drug discontinuation and individual composite item occurrence. We will estimate
      the effects of treatment in a 2-year follow-up period, using time-to-event models
      with propensity score adjustment to control confounding. Secondary analyses will
      examine 'as treated' outcomes. ETHICS AND DISSEMINATION: The protocol, data
      creation plan, privacy impact statement and data sharing agreements have been
      approved. Dissemination is planned via conferences and publications as well as
      directly to drug policy leaders. Information on the overall comparative
      effectiveness and safety of DOACs versus warfarin in a country with high quality
      anticoagulation management, as well as for vulnerable subgroups, will be an
      important addition to the literature.

PMID- 27884851
TI  - Influence of preinfarction angina and coronary collateral blood flow on the
      efficacy of remote ischaemic conditioning in patients with ST segment elevation
      myocardial infarction: post hoc subgroup analysis of a randomised controlled
      trial.
AB  - OBJECTIVES: Remote ischaemic conditioning (RIC) confers cardioprotection in
      patients with ST segment elevation myocardial infarction (STEMI) undergoing
      primary percutaneous coronary intervention (pPCI). We investigated whether
      preinfarction angina and coronary collateral blood flow (CCBF) to the infarct
      related artery modify the efficacy of RIC. DESIGN: Post hoc subgroup analysis of
      a randomised controlled trial. PARTICIPANTS: A total of 139 patients with STEMI
      randomised to treatment with pPCI or RIC+pPCI. INTERVENTIONS: RIC was performed
      prior to pPCI as four cycles of 5 min upper arm ischaemia and reperfusion with a
      blood pressure cuff. PRIMARY OUTCOME MEASURE: Myocardial salvage index (MSI)
      assessed by single-photon emission computerised tomography. We evaluated the
      efficacy of RIC in subgroups of patients with or without preinfarction angina or
      CCBF. RESULTS: Of 139 patients included in the study, 109 had available data for
      preinfarction angina status and 54 had preinfarction angina. Among 83 patients
      with Thrombolysis In Myocardial Infarction flow 0/1 on arrival, 43 had CCBF.
      Overall, RIC+pPCI increased median MSI compared with pPCI alone (0.75 vs 0.56,
      p=0.045). Mean MSI did not differ between patients with and without preinfarction
      angina in either the pPCI alone (0.58 and 0.57; 95% CI -0.17 to 0.19, p=0.94) or
      the RIC+pPCI group (0.66 and 0.69; 95% CI -0.18 to 0.10, p=0.58). Mean MSI did
      not differ between patients with and without CCBF in the pPCI alone group (0.51
      and 0.55; 95% CI -0.20 to 0.13, p=0.64), but was increased in patients with CCBF
      versus without CCBF in the RIC+pPCI group (0.75 vs 0.58; 95% CI 0.03 to 0.31,
      p=0.02; effect modification from CCBF on the effect of RIC on MSI, p=0.06).
      CONCLUSIONS: Preinfarction angina did not modify the efficacy of RIC in patients
      with STEMI undergoing pPCI. CCBF to the infarct-related artery seems to be of
      importance for the cardioprotective efficacy of RIC. TRIAL REGISTRATION NUMBER:
      NCT00435266, Post-results.

PMID- 27884852
TI  - Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma
      (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) is an asbestos-related cancer,
      which is difficult to diagnose. Thoracoscopy is frequently required but is not
      widely available. An accurate, non-invasive diagnostic biomarker would allow
      early specialist referral, limit diagnostic delays and maximise clinical trial
      access. Current markers offer insufficient sensitivity and are not routinely
      used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated
      sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM
      (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma)
      is a suitably powered, multicentre, prospective observational study designed to
      determine whether these markers provide clinically useful diagnostic and
      prognostic information. METHODS AND ANALYSIS: Serum and plasma (for SOMAscan and
      fibulin-3, respectively) will be collected at presentation, prior to pleural
      biopsy/pleurodesis, from 83 to 120 patients with MPM, at least 480 patients with
      non-MPM pleural disease and 109 asbestos-exposed controls. Final numbers of
      MPM/non-MPM cases will depend on the incidence of MPM in the study population
      (estimated at 13-20%). Identical sampling and storage protocols will be used in
      22 recruiting centres and histological confirmation sought in all cases. Markers
      will be measured using the SOMAscan proteomic assay (SomaLogic) and a
      commercially available fibulin-3 ELISA (USCN Life Science). The SE in the
      estimated sensitivity and specificity will be <5% for each marker and their
      performance will be compared with serum mesothelin. Blood levels will be compared
      with paired pleural fluid levels and MPM tumour volume (using MRI) in a nested
      substudy. The prognostic value of each marker will be assessed and a large
      bioresource created. ETHICS AND DISSEMINATION: The study has been approved by the
      West of Scotland Research Ethics Committee (Ref: 13/WS/0240). A Trial Management
      Group meets on a monthly basis. Results will be published in peer-reviewed
      journals, presented at international meetings and disseminated to patient groups.
      TRIAL REGISTRATION NUMBER: ISRCTN10079972, Pre-results.

PMID- 27884853
TI  - Gyejibongneyong-hwan, a herbal medicine for the treatment of dysmenorrhoea with
      uterine fibroids: a protocol for a randomised controlled trial.
AB  - INTRODUCTION: Gyejibongneyong-hwan (GBH), or the Guizhi Fuling Formula in
      Chinese, is widely used to treat uterine fibroids in East Asian countries
      including Korea, China and Japan. This study will assess the efficacy and safety
      of the GBH formula for the treatment of dysmenorrhoea. METHODS AND ANALYSIS: This
      study will be a randomised double-blind controlled trial with two parallel arms:
      the GBH group and the placebo group. This trial will recruit 38 women between 18
      and 45 years of age with secondary dysmenorrhoea with uterine fibroids. The
      investigational drugs, either GBH or placebo, will be administered to the
      participants three times per day for two menstrual periods (8 weeks). The
      participants will be followed up for three menstrual cycles after administration
      of the drugs. The primary outcome will be the Numeric Rating Scale score of
      average menstrual pain. All analyses will be performed with SAS (V.9.1.3; SAS
      Institute, Cary, North Carolina, USA) by a statistician blinded to the allocation
      of the groups. Statistical analysis will be undertaken on the intent-to-treat
      (ITT) basis with a 95% CI using the last observation carried forward for missing
      values. The ITT analysis will include all randomised patients. ETHICS AND
      DISSEMINATION: This research protocol has been reviewed and approved by the
      institutional review boards of the trial centre (number WSOH IRB 1606-03).
      Written informed consent will be obtained from all study participants prior to
      enrolment in the study. The results will be published in a peer-reviewed journal
      and will be disseminated electronically and in print. TRIAL REGISTRATION NUMBER:
      KCT0001967.

PMID- 27884854
TI  - Cross-sectional assessment of patient attitudes towards participation in clinical
      trials: does making results publicly available matter?
AB  - OBJECTIVES: Previous studies have shown that a majority of patients cite
      altruistic motives, such as contributing to generalisable medical knowledge, as
      factors motivating clinical trial participation. We sought to examine the impact
      of making trial results publicly available on patients' willingness to
      participate in clinical research. DESIGN: Cross-sectional analysis using a
      questionnaire developed by a panel with expertise in publication bias, informed
      consent and survey design. SETTING: A single urban, academic emergency department
      (ED) in the Northeastern USA. PARTICIPANTS: 799 ED patients. OUTCOME MEASURES: We
      assessed (1) participants' attitudes towards clinical trial participation, and
      (2) the impact of whether study results would eventually be made publicly
      available or not on willingness to participate in a trial. RESULTS: Of 799
      patients surveyed, 36% (95% CI 32% to 39%) reported that they would generally
      like to participate in a trial, and another 50% (95% CI 47% to 54%) reported that
      they would consider participation depending on study details. For the majority of
      participants, the publication of trial results was either important (36%; 95% CI
      33% to 40%) or very important (48%; 95% CI 44% to 51%). Most (63%; 95% CI 59% to
      66%) reported they would be less likely to participate in a trial if
      investigators had not publicly released results from a prior study. Additionally,
      85% (95% CI 82% to 87%) felt that it was important or very important to receive
      information about the publication track record of sponsors and investigators
      during the informed consent process. CONCLUSIONS: The majority of patients in
      this sample would consider participation in a clinical trial. Patients value the
      public release of trial results, and believe that the informed consent process
      should address the possibility of non-publication.

PMID- 27884855
TI  - Effectiveness of trauma-focused psychological therapies compared to usual
      postnatal care for treating post-traumatic stress symptoms in women following
      traumatic birth: a systematic review protocol.
AB  - INTRODUCTION: Maternal mental health has been largely neglected in the
      literature. Women, however, may be vulnerable to developing post-traumatic stress
      symptoms or post-traumatic stress disorder (PTSD), following traumatic birth. In
      turn, this may affect their capacity for child rearing and ability to form a
      secure bond with their baby and impact on the wider family. Trauma-focused
      psychological therapies (TFPT) are widely regarded as effective and acceptable
      interventions for PTSD in general and clinical populations. Relatively little is
      known about the effectiveness of TFPT for women postpartum who have post
      traumatic stress symptoms. METHODS AND ANALYSIS: We will conduct a review to
      assess the effectiveness of TFPT, compared with usual postpartum care, as a
      treatment for post-traumatic stress symptoms or PTSD for women following
      traumatic birth. Using a priori search criteria, we will search for randomised
      controlled trials (RCT) in four databases: Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, PsycINFO and OpenGrey. We will use search
      terms that relate to the population, TFPT and comparators. Screening of search
      results and data extraction will be undertaken by two reviewers, independently.
      Risk of bias will be assessed in RCTs which meet the review criteria. Data will
      be analysed using the following methods, as appropriate: narrative synthesis;
      meta-analysis; subgroup analysis and meta-regression. DISSEMINATION AND ETHICS:
      As this work comprises a synthesis of existing studies, ethical approvals are not
      required. Results will be disseminated at conferences and in publications.

PMID- 27884856
TI  - A refugee camp in the centre of Europe: clinical characteristics of asylum
      seekers arriving in Brussels.
AB  - BACKGROUND: In the summer of 2015, the exodus of Syrian war refugees and
      saturation of refugee camps in neighbouring countries led to the influx of asylum
      seekers in European countries, including Belgium. This study aims to describe the
      demographic and clinical characteristics of asylum seekers who arrived in a
      huddled refugee camp, in the centre of a well-developed country with all medical
      facilities. METHODS: Using a descriptive cross-sectional study design, physicians
      of Medecins du Monde prospectively registered age, gender, origin, medical
      symptoms and diagnoses of all patients presenting to an erected field hospital in
      Brussels in September 2015. Diagnoses were post hoc categorised according to the
      International Classification of Diseases. RESULTS: Of 4037 patients examined in
      the field hospital, 3907 were included and analysed for this study. Over 11% of
      patients suffered from injuries, but these were outnumbered by the proportion of
      patients with respiratory (36%), dental (9%), skin (9%) and digestive (8%)
      diagnoses. More than 49% had features of infections at the time of the
      consultation. CONCLUSIONS: Asylum seekers arriving in a refugee camp in Brussels
      after a long and hazardous journey suffer mostly from respiratory, dental, skin
      and digestive diseases. Still, one in seven suffers from injury. These findings,
      consistent with other reports, should be anticipated when composing emergency
      medical teams and interagency emergency health or similar kits to be used in a
      field hospital, even in a Western European country. TRIAL REGISTRATION NUMBER:
      ISRCTN13523620, Results.

PMID- 27884857
TI  - Implementing shared decision-making in interprofessional home care teams (the
      IPSDM-SW study): protocol for a stepped wedge cluster randomised trial.
AB  - INTRODUCTION: The frail elderly in Canada face a tough decision when they start
      to lose autonomy: whether to stay at home or move to another location. This study
      seeks to scale up and evaluate the implementation of shared decision-making (SDM)
      in interprofessional (IP) home care teams caring for elderly clients or their
      caregivers facing a decision about staying at home or moving elsewhere. METHODS:
      A stepped wedge cluster randomised trial involving 8 Health and Social Service
      Centers (HSSCs) will be conducted with IP home care teams. HSSCs are the unit of
      randomisation. A decision guide will be passively distributed to all of the
      participating HSSCs at the beginning of the project. The participating HSSCs will
      then be randomised to 1 of 4 intervention start times, separated by 7-month
      intervals. The primary outcome is whether or not clients and caregivers assumed
      an active role in decision-making, assessed with a modified version of the
      Control Preferences Scale. The intervention, targeted at IP home care teams,
      consists of a 1.5 hour online tutorial and a 3.5 hour skills building workshop in
      IP SDM. Clients will be eligible for outcome assessment if they (1) are aged
      >=65; (2) are receiving care from the IP home care team of the enrolled HSSCs;
      (3) have made a decision about whether to stay at home or move to another
      location during the recruitment periods; (4) are able to read, understand and
      write French or English; (5) can give informed consent. If clients are not able
      to provide informed consent, their primary caregiver will become the eligible
      participant. ETHICS AND DISSEMINATION: Ethics committee review approval has been
      obtained from the Multicenter Ethics Committee of CISSS-Laval. Results will be
      disseminated at conferences, on websites of team members and in peer-reviewed and
      professional journals intended for policymakers and managers. TRIAL REGISTRATION
      NUMBER: NCT02592525, Pre-results.

PMID- 27884859
TI  - Isolated GNRH deficiency: genotypic and phenotypic characteristics of the
      genetically heterogeneous Greek population.

PMID- 27884858
TI  - Hemicraniectomy versus medical treatment with large MCA infarct: a review and
      meta-analysis.
AB  - OBJECTIVE: Large middle cerebral artery stroke (space-occupying middle-cerebral
      artery (MCA) infarction (SO-MCAi)) results in a very high incidence of death and
      severe disability. Decompressive hemicraniectomy (DHC) for SO-MCAi results in
      large reductions in mortality; the level of function in the survivors, and
      implications, remain controversial. To address the controversy, we pooled
      available randomised controlled trials (RCTs) that examined the impact of DHC on
      survival and functional ability in patients with large SO-MCAi and cerebral
      oedema. METHODS: We searched MEDLINE, EMBASE and Cochrane library databases for
      randomised controlled trials (RCTs) enrolling patients suffering SO-MCAi
      comparing conservative management to DHC administered within 96 hours after
      stroke symptom onset. Outcomes were death and disability measured by the modified
      Rankin Scale (mRS). We used a random effects meta-analytical approach with
      subgroup analyses (time to treatment and age). We applied GRADE methods to rate
      quality/confidence/certainty of evidence. RESULTS: 7 RCTs were eligible (n=338
      patients). We found DHC reduced death (69-30% in medical vs surgical groups, 39%
      fewer), and increased the number of patients with mRS of 2-3 (slight to moderate
      disability: 14-27%, increase of 13%), those with mRS 4 (severe disability: 10
      32%, increase of 22%) and those with mRS 5 (very severe disability 7-11%:
      increase of 4%) (all differences p<0.0001). We judged
      quality/confidence/certainty of evidence high for death, low for functional
      outcome mRS 0-3, and moderate for mRS 0-4 (wide CIs and problems in concealment,
      blinding of outcome assessors and stopping early). CONCLUSIONS: DHC in SO-MCAi
      results in large reductions in mortality. Most of those who would otherwise have
      died are left with severe or very severe disability: for example, inability to
      walk and a requirement for help with bodily needs, though uncertainty about the
      proportion with very severe, severe and moderate disability remains (low to
      moderate quality/confidence/certainty evidence).

PMID- 27884860
TI  - Using technology to measure daily and weekly movement patterns in exercise
      medicine patients.

PMID- 27884861
TI  - Diagnostic accuracy of the Ottawa Ankle and Midfoot Rules: a systematic review
      with meta-analysis.
AB  - OBJECTIVE: To review the diagnostic accuracy of the Ottawa Ankle and Midfoot
      Rules and explore if clinical features and/or methodological quality of the study
      influence diagnostic accuracy estimates. DESIGN: Systematic review with meta
      analysis. DATA SOURCES: MEDLINE, EMBASE, CINAHL, SPORTDiscus and Cochrane
      Library. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Primary diagnostic studies
      reporting the accuracy of the Rules in people with ankle and/or midfoot injury
      were retrieved. Diagnostic accuracy estimates, overall and for subgroups
      (patient's age, profession of the assessor and setting of application), were
      made. Sensitivity analyses included studies with a low risk of bias and studies
      where all patients received radiographs. RESULTS: 66 studies were included. Ankle
      and Midfoot Rules presented similar accuracies, which were homogeneous and high
      for sensitivity and negative likelihood ratios and poor and heterogeneous for
      specificity and positive likelihood ratios (mean, 95% CI pooled sensitivity of
      Ankle Rules: 99.4%, 97.9% to 99.8%; specificity: 35.3%, 28.8% to 42.3%).
      Sensitivity of the Ankle Rules was higher in adults than in children, but the
      profession of the assessor did not appear to influence accuracy. Specificity was
      higher for Midfoot than for Ankle Rules. There were not enough studies to allow
      comparison according to setting of application. Studies with a low risk of bias
      and where all patients received radiographs provided lower accuracy estimates.
      Specificity heterogeneity was not explained by assessor training, use of imaging
      in all patients and low risk of bias. CONCLUSIONS: Study features and the
      methodological quality influence estimates of the diagnostic accuracy of the
      Ottawa Ankle and Midfoot Rules.

PMID- 27884863
TI  - Misinterpretations of the 'p value': a brief primer for academic sports medicine.

PMID- 27884862
TI  - Associations of occupational standing with musculoskeletal symptoms: a systematic
      review with meta-analysis.
AB  - OBJECTIVE: Given the high exposure to occupational standing in specific
      occupations, and recent initiatives to encourage intermittent standing among
      white-collar workers, a better understanding of the potential health consequences
      of occupational standing is required. We aimed to review and quantify the
      epidemiological evidence on associations of occupational standing with
      musculoskeletal symptoms. DESIGN: A systematic review was performed. Data from
      included articles were extracted and described, and meta-analyses conducted when
      data were sufficiently homogeneous. DATA SOURCES: Electronic databases were
      systematically searched. ELIGIBILITY CRITERIA: Peer-reviewed articles on
      occupational standing and musculoskeletal symptoms from epidemiological studies
      were identified. RESULTS: Of the 11 750 articles screened, 50 articles reporting
      49 studies were included (45 cross-sectional and 5 longitudinal; n=88 158
      participants) describing the associations of occupational standing with
      musculoskeletal symptoms, including low-back (39 articles), lower extremity (14
      articles) and upper extremity (18 articles) symptoms. In the meta-analysis,
      'substantial' (>4 hours/workday) occupational standing was associated with the
      occurrence of low-back symptoms (pooled OR (95% CI) 1.31 (1.10 to 1.56)).
      Evidence on lower and upper extremity symptoms was too heterogeneous for meta
      analyses. The majority of included studies reported statistically significant
      detrimental associations of occupational standing with lower extremity, but not
      with upper extremity symptoms. CONCLUSIONS: The evidence suggests that
      substantial occupational standing is associated with the occurrence of low-back
      and (inconclusively) lower extremity symptoms, but there may not be such an
      association with upper extremity symptoms. However, these conclusions are
      tentative as only limited evidence was found from high-quality, longitudinal
      studies with fully adjusted models using objective measures of standing.

PMID- 27884864
TI  - Sports injuries and illnesses in the Lillehammer 2016 Youth Olympic Winter Games.
AB  - BACKGROUND: Injury and illness surveillance during high-level youth sports events
      is an important first step in health prevention and caretaking of the young elite
      athletes. AIM: To analyse injuries and illnesses that occurred during the 10 days
      2nd Youth Olympic Winter Games (YOG), held in Lillehammer 2016. METHODS: We
      recorded the daily occurrence (or non-occurrence) of injuries and illnesses
      through the reporting of (1) all National Olympic Committee (NOC) medical teams
      and (2) the polyclinic and medical venues by the Lillehammer Organising Committee
      (LYOCOG) medical staff. RESULTS: In total, 1083 athletes (48 double-starters),
      46% (n=502) of them females, from 70 NOCs were registered in the study. NOCs and
      LYOCOG reported 108 injuries and 81 illnesses, equalling to 9.5 injuries and 7.2
      illnesses per 100 athletes. The percentage of injured athletes was highest in the
      snowboard and ski slopestyle and cross disciplines, alpine skiing and skeleton,
      and lowest in the Nordic skiing disciplines. Approximately, two-thirds of the
      injuries (n=71, 65.7%) prevented the athlete from training or competition, while
      10 injuries (9.3%) were registered with an estimated absence from sport for >7
      days. The rate of illness was highest in curling and the Nordic skiing
      disciplines with most of them being respiratory tract infections (81.5%).
      CONCLUSIONS: Overall, 9% of the athletes incurred at least one injury during the
      games, and 7% an illness, which is similar to the first YOG in Innsbruck 2012 and
      slightly lower compared with previous Winter Olympic Games. The incidence of
      injuries and illnesses varied substantially between sports.

PMID- 27884865
TI  - Running exposure is associated with the risk of hamstring strain injury in elite
      Australian footballers.
AB  - BACKGROUND: To investigate the association between running exposure and the risk
      of hamstring strain injury (HSI) in elite Australian footballers. METHODS: Elite
      Australian footballers (n=220) from 5 different teams participated. Global
      positioning system (GPS) data were provided for every athlete for each training
      session and match for the entire 2015 season. The occurrences of HSIs throughout
      the study period were reported. Receiver operator characteristic curve analyses
      were performed and the relative risk (RR) of subsequent HSI was calculated for
      absolute and relative running exposure variables related to distance covered
      above 10 and 24 km/hour in the preceding week/s. RESULTS: 30 prospective HSIs
      occurred. For the absolute running exposure variables, weekly distance covered
      above 24 km/hour (>653 m, RR=3.4, 95% CI 1.6 to 7.2, sensitivity=0.52,
      specificity=0.76, area under the curve (AUC)=0.63) had the largest influence on
      the risk of HSI in the following week. For the relative running exposure
      variables, distance covered above 24 km/hour as a percentage of distance covered
      above 10 km/hour (>2.5%, RR=6.3, 95% CI 1.5 to 26.7, sensitivity=0.93,
      specificity=0.34, AUC=0.63) had the largest influence on the risk of HSI in the
      following week. Despite significant increases in the RR of HSI, the predictive
      capacity of these variables was limited. CONCLUSIONS: An association exists
      between absolute and relative running exposure variables and elite Australian
      footballers' risk of subsequent HSI, with the association strongest when
      examining data within 7-14 days. Despite this, the use of running exposure
      variables displayed limited clinical utility to predict HSI at the individual
      level.

PMID- 27884866
TI  - A Case of Specific Language Impairment in a Deaf Signer of American Sign
      Language.
AB  - This article describes the case of a deaf native signer of American Sign Language
      (ASL) with a specific language impairment (SLI). School records documented normal
      cognitive development but atypical language development. Data include school
      records; interviews with the child, his mother, and school professionals; ASL and
      English evaluations; and a comprehensive neuropsychological and psychoeducational
      evaluation, and they span an approximate period of 7.5 years (11;10-19;6)
      including scores from school records (11;10-16;5) and a 3.5-year period (15;10
      19;6) during which we collected linguistic and neuropsychological data. Results
      revealed that this student has average intelligence, intact visual perceptual
      skills, visuospatial skills, and motor skills but demonstrates challenges with
      some memory and sequential processing tasks. Scores from ASL testing signaled
      language impairment and marked difficulty with fingerspelling. The student also
      had significant deficits in English vocabulary, spelling, reading comprehension,
      reading fluency, and writing. Accepted SLI diagnostic criteria exclude deaf
      individuals from an SLI diagnosis, but the authors propose modified criteria in
      this work. The results of this study have practical implications for
      professionals including school psychologists, speech language pathologists, and
      ASL specialists. The results also support the theoretical argument that SLI can
      be evident regardless of the modality in which it is communicated.

PMID- 27884867
TI  - Narrative medicine and death in the ICU: word clouds as a visual legacy.
AB  - OBJECTIVE: The Word Cloud is a frequent wish in the 3 Wishes Project developed to
      nurture peace and ease the grieving process for dying critically ill patients.
      The objective was to examine whether Word Clouds can act as a heuristic approach
      to encourage a narrative orientation to medicine. Narrative medicine is an
      approach which can strengthen relationships, compassion and resilience. DESIGN:
      Word Clouds were created for 42 dying patients, and we interviewed 37 family
      members and 73 clinicians about their impact. We conducted a directed qualitative
      content analysis, using the 3 stages of narrative medicine (attention,
      representation, affiliation) to examine the narrative medicine potential of Word
      Clouds. RESULTS: The elicitation of stories for the Word Cloud promotes narrative
      attention to the patient as a whole person. The distillation of these stories
      into a list of words and the prioritisation of those words for arrangement in the
      collage encourages a representation that did not enforce a beginning, middle or
      end to the story of the patient's life. Strong affiliative connections were
      achieved through the honouring of patients, caring for families and sharing of
      memories encouraged through the creation, sharing and discussion of Word Clouds.
      CONCLUSIONS: In the 3 Wishes Project, Word Clouds are 1 way that families and
      clinicians honour a dying patient. Engaging in the process of making a Word Cloud
      can promote a narrative orientation to medicine, forging connections, making
      meaning through reminiscence and leaving a legacy of a loved one. Documenting and
      displaying words to remember someone in death reaffirms their life.

PMID- 27884870
TI  - Development and Validation of an LC-ESI-MS/MS Method for Simultaneous
      Determination of Ligustroflavone and Rhoifolin in Rat Plasma and Its Application
      to a Pharmacokinetic Study.
AB  - A selective and sensitive liquid chromatography-electrospray ionization tandem
      mass spectrometry (LC-ESI-MS/MS) method was developed for the simultaneous
      determination of ligustroflavone and rhoifolin in rat plasma. Chromatographic
      separation was performed on a Venusil HILIC column using an isocratic mobile
      phase consisting of acetonitrile/water/formic acid (75:25:0.1, v/v/v). The
      detection was achieved using a triple-quadrupole tandem MS in negative ionization
      through selected reaction monitoring (SRM) mode. The calibration curves of both
      analytes in plasma showed good linearity over the concentration ranges of 3-300
      ng/mL for ligustroflavone, and 2-200 ng/mL for rhoifolin. This assay was used to
      investigate the pharmacokinetics of ligustroflavone and rhoifolin in rats.

PMID- 27884868
TI  - Combined associations of body weight and lifestyle factors with all cause and
      cause specific mortality in men and women: prospective cohort study.
AB  - OBJECTIVE:  To evaluate the combined associations of diet, physical activity,
      moderate alcohol consumption, and smoking with body weight on risk of all cause
      and cause specific mortality. DESIGN:  Longitudinal study with up to 32 years of
      follow-up. SETTING:  Nurses' Health Study (1980-2012) and Health Professionals
      Follow-up Study (1986-2012). PARTICIPANTS:  74 582 women from the Nurses' Health
      Study and 39 284 men from the Health Professionals Follow-up Study who were free
      from cardiovascular disease and cancer at baseline. MAIN OUTCOME MEASURES: 
      Exposures included body mass index (BMI), score on the alternate healthy eating
      index, level of physical activity, smoking habits, and alcohol drinking while
      outcome was mortality (all cause, cardiovascular, cancer). Cox proportional
      hazard models were used to calculate the adjusted hazard ratios of all cause,
      cancer, and cardiovascular mortality with their 95% confidence intervals across
      categories of BMI, with 22.5-24.9 as the reference. RESULTS:  During up to 32
      years of follow-up, there were 30 013 deaths (including 10 808 from cancer and
      7189 from cardiovascular disease). In each of the four categories of BMI studied
      (18.5-22.4, 22.5-24.9, 25-29.9, >=30), people with one or more healthy lifestyle
      factors had a significantly lower risk of total, cardiovascular, and cancer
      mortality than individuals with no low risk lifestyle factors. A combination of
      at least three low risk lifestyle factors and BMI between 18.5-22.4 was
      associated with the lowest risk of all cause (hazard ratio 0.39, 95% confidence
      interval 0.35 to 0.43), cancer (0.40, 0.34 to 0.47), and cardiovascular (0.37,
      0.29 to 0.46) mortality, compared with those with BMI between 22.5-24.9 and none
      of the four low risk lifestyle factors. CONCLUSION:  Although people with a
      higher BMI can have lower risk of premature mortality if they also have at least
      one low risk lifestyle factor, the lowest risk of premature mortality is in
      people in the 18.5-22.4 BMI range with high score on the alternate healthy eating
      index, high level of physical activity, moderate alcohol drinking, and who do not
      smoke. It is important to consider diet and lifestyle factors in the evaluation
      of the association between BMI and mortality.

PMID- 27884871
TI  - Simultaneous Liquid Chromatographic Determination of Ebastine with Two
      Sympathomimetic Drugs Using a Monolithic Column.
AB  - Ebastine (EBS) has been assayed in its laboratory-prepared co-formulated tablets
      with either pseudoephedrine hydrochloride (PSU) or phenylephrine hydrochloride
      (PHR) using isocratic reversed-phase chromatography. Separation was conducted
      using a 50 mm * 4.6 mm i.d., Chromolith(r) SpeedROD RP-18 end-capped column at
      ambient temperature. A mobile phase composed of water:acetonitrile in a ratio of
      25:75 having a pH of 3.2, has been utilized at 1 mL/min with UV detection at 254
      nm for both EBS and PSU and 274 nm for PHR which in turn increased the
      sensitivity of the proposed method significantly. Symmetric well-separated peaks
      resulted in a short chromatographic run; <5 min. The proposed method was
      subjected to detailed validation procedures and proved to be highly sensitive as
      shown from limit of quantification values which were 4.7, 39.4 and 10.2 MUg/mL
      for EBS, PSU and PHR, respectively. The proposed method was used to analyze EBS
      in its laboratory-prepared co-formulated tablets; the obtained results were
      comparable to those resulting from the reference method.

PMID- 27884869
TI  - Sex based subgroup differences in randomized controlled trials: empirical
      evidence from Cochrane meta-analyses.
AB  - OBJECTIVE:  To evaluate the frequency, validity, and relevance of statistically
      significant (P<0.05) sex-treatment interactions in randomized controlled trials
      in Cochrane meta-analyses. DESIGN:  Meta-epidemiological study. DATA SOURCES: 
      Cochrane Database of Systematic Reviews (CDSR) and PubMed. ELIGIBILITY CRITERIA
      FOR STUDY SELECTION:  Reviews published in the CDSR with sex-treatment subgroup
      analyses in the forest plots, using data from randomized controlled trials. DATA
      EXTRACTION:  Information on the study design and sex subgroup data were extracted
      from reviews and forest plots that met inclusion criteria. For each statistically
      significant sex-treatment interaction, the potential for biological plausibility
      and clinical significance was considered. RESULTS:  Among the 41 reviews with
      relevant data, there were 109 separate treatment-outcome analyses ("topics").
      Among the 109 topics, eight (7%) had a statistically significant sex-treatment
      interaction. The 109 topics included 311 randomized controlled trials (162 with
      both sexes, 46 with males only, 103 with females only). Of the 162 individual
      randomized controlled trials that included both sexes, 15 (9%) had a
      statistically significant sex-treatment interaction. Of four topics where the
      first published randomized controlled trial had a statistically significant sex
      treatment interaction, no meta-analyses that included other randomized controlled
      trials retained the statistical significance and no meta-analyses showed
      statistical significance when data from the first published randomized controlled
      trial were excluded. Of the eight statistically significant sex-treatment
      interactions from the overall analyses, only three were discussed by the CDSR
      reviewers for a potential impact on different clinical management for males
      compared with females. None of these topics had a sex-treatment interaction that
      influenced treatment recommendations in recent guidelines. UpToDate, an online
      physician-authored clinical decision support resource, suggested differential
      management of men and women for one of these sex-treatment interactions.
      CONCLUSION:  Statistically significant sex-treatment interactions are only
      slightly more frequent than what would be expected by chance and there is little
      evidence of subsequent corroboration or clinical relevance of sex-treatment
      interactions.

PMID- 27884872
TI  - An HPLC Procedure for the Quantification of Aloin in Latex and Gel from Aloe
      barbadensis Leaves.
AB  - Aloin is an anthraquinone-C-glycoside present in Aloe vera. This compound is
      extremely variable among different species and highly depends on the growing
      conditions of the plants. The quantification of aloin in different extraction
      preparations has been a frequent problem due to the high instability of the
      compound. The aim of the present study is to develop and validated an analytical
      method for aloin detection in fresh and dry samples of Aloe barbadensis gel and
      latex using high performance liquid chromatography coupled to a diode array
      detector (HPLC-DAD). Phosphate buffered saline (pH 3) was selected as the
      extraction solvent. The aloin was separated using a Zorbax Eclipse AAA column
      (4.6 * 150 mm) at 35 degrees C, and water and acetonitrile were used as the
      mobile phase at a flow rate of 0.9 mL/min. The linearity was satisfactory with a
      correlation coefficient greater than 0.999. Under these conditions, the method
      precision (relative standard deviation) was 3.71% for FL, 4.41% for dry latex,
      0.81% for fresh gel and 4.42% for dry gel samples. Aloe latex was determined to
      have a greater amount of aloin than aloe gel. The method validation was
      satisfactory and exhibited adequate linearity, repeatability and accuracy.

PMID- 27884873
TI  - Optimization of Robust HPLC Method for Quantitation of Ambroxol Hydrochloride and
      Roxithromycin Using a DoE Approach.
AB  - The aim of this work was to develop and optimize a robust HPLC method for the
      separation and quantitation of ambroxol hydrochloride and roxithromycin utilizing
      Design of Experiment (DoE) approach. The Plackett-Burman design was used to
      assess the impact of independent variables (concentration of organic phase,
      mobile phase pH, flow rate and column temperature) on peak resolution, USP
      tailing and number of plates. A central composite design was utilized to evaluate
      the main, interaction, and quadratic effects of independent variables on the
      selected dependent variables. The optimized HPLC method was validated based on
      ICH Q2R1 guideline and was used to separate and quantify ambroxol hydrochloride
      and roxithromycin in tablet formulations. The findings showed that DoE approach
      could be effectively applied to optimize a robust HPLC method for quantification
      of ambroxol hydrochloride and roxithromycin in tablet formulations. Statistical
      comparison between results of proposed and reported HPLC method revealed no
      significant difference; indicating the ability of proposed HPLC method for
      analysis of ambroxol hydrochloride and roxithromycin in pharmaceutical
      formulations.

PMID- 27884874
TI  - Development and Validation of a Sensitive LC-MS-MS Method for Quantification of
      Mogrol in Rat Plasma and Application to Pharmacokinetic Study.
AB  - Mogrol, the aglycone of mogrosides, is a potential pharmacologically active
      ingredient isolated from the fruits of Siraitia grosvenorii. The aim of this
      study was to develop and validate an LC-MS-MS method for the quantification of
      mogrol in rat plasma. Protein precipitation extraction procedure using
      methanol/water (1:1, v/v) was employed to extract mogrol from rat plasma.
      Chromatographic separation was performed on a reverse-phase Agilent Zorbax XDB
      C18 column (50 mm * 2.1 mm, 3.5 MUm) with gradient elution using a mobile phase
      containing methanol and water, both of which contained 0.1% formic acid at a flow
      rate of 0.50 mL/min. The analyte was monitored by tandem-mass spectrometry with
      positive electrospray ionization mode. The precursor/product transitions (m/z) in
      the positive ion mode were 459.3->423.3 and 386.2->122.3 for mogrol and internal
      standard, respectively. The method was validated over the concentration range of
      10.0-10,000 ng/mL with a lower limit of quantification of 10.0 ng/mL in rat
      plasma. Validation experiments included tests for specificity, precision,
      accuracy, matrix effect, and stability under different storage and handling
      conditions. This method was successfully utilized to pharmacokinetic evaluation
      of mogrol after intravenous and oral administration of a single dose in rats at
      2.0 and 5.0 mg/kg, respectively. The oral absolute bioavailability (F) of mogrol
      was estimated to be 10.3 +/- 2.15% with an elimination half-life (t1/2) value of
      2.41 +/- 0.11 h.

PMID- 27884876
TI  - Measurement of Cortical Thickness and Volume of Subcortical Structures in
      Multiple Sclerosis: Agreement between 2D Spin-Echo and 3D MPRAGE T1-Weighted
      Images.
AB  - BACKGROUND AND PURPOSE: Gray matter pathology is known to occur in multiple
      sclerosis and is related to disease outcomes. FreeSurfer and the FMRIB Integrated
      Registration and Segmentation Tool (FIRST) have been developed for measuring
      cortical and subcortical gray matter in 3D-gradient-echo T1-weighted images.
      Unfortunately, most historical MS cohorts do not have 3D-gradient-echo, but 2D
      spin-echo images instead. We aimed to evaluate whether cortical thickness and the
      volume of subcortical structures measured with FreeSurfer and FIRST could be
      reliably measured in 2D-spin-echo images and to investigate the strength and
      direction of clinicoradiologic correlations. MATERIALS AND METHODS: Thirty-eight
      patients with MS and 2D-spin-echo and 3D-gradient-echo T1-weighted images
      obtained at the same time were analyzed by using FreeSurfer and FIRST. The
      intraclass correlation coefficient between the estimates was obtained.
      Correlation coefficients were used to investigate clinicoradiologic associations.
      RESULTS: Subcortical volumes obtained with both FreeSurfer and FIRST showed good
      agreement between 2D-spin-echo and 3D-gradient-echo images, with 68.8%-76.2% of
      the structures having either a substantial or almost perfect agreement.
      Nevertheless, with FIRST with 2D-spin-echo, 18% of patients had mis-segmentation.
      Cortical thickness had the lowest intraclass correlation coefficient values, with
      only 1 structure (1.4%) having substantial agreement. Disease duration and the
      Expanded Disability Status Scale showed a moderate correlation with most of the
      subcortical structures measured with 3D-gradient-echo images, but some
      correlations lost significance with 2D-spin-echo images, especially with FIRST.
      CONCLUSIONS: Cortical thickness estimates with FreeSurfer on 2D-spin-echo images
      are inaccurate. Subcortical volume estimates obtained with FreeSurfer and FIRST
      on 2D-spin-echo images seem to be reliable, with acceptable clinicoradiologic
      correlations for FreeSurfer.

PMID- 27884875
TI  - Identification and Determination of Phenolics in Lamiaceae Species by UPLC-DAD
      ESI-MS/MS.
AB  - This study reports the phenolic profile screening of aromatic Lamiaceae species
      such as marjoram (Origanum majorana L.), lavender (Lavandula officinalis) and
      pennyroyal (Mentha pulegium L.) using a novel and validated ultra performance
      liquid chromatography method coupled with DAD diode array detector and tandem
      mass spectrometry (MS/MS) in negative mode of electrospray ionization.
      Identification and quantification of phenolics in these plant extracts has been
      realized within 12 min. This method showed good precision (percentage relative
      standard deviation; RSD% 0.54-2.72 for intra-day, 1.71-4.64 for inter-day),
      reproducibility (percentage recovery, REC% 92.0-109.0) and linearity (r = 0.9988
      0.9999). Limits of detection ranged from 0.02 to 18.2 ng/mL. The extraction of
      plants was performed using microwave-assisted extraction technique and 60% (v/v)
      aqueous methanol solvent medium was selected as suitable solvent because of
      maximum extraction efficiency. Total antioxidant capacity, total phenolic content
      and free radical scavenging activity of these plant extracts were tested and the
      results correlated well among each other. According to the Folin assay, phenolic
      contents of Origanum majorana L., Mentha pulegium L. and Lavandula officinalis
      were calculated as 119 +/- 3.4, 85.1 +/- 2.8 and 57.8 +/- 2.1 mg GAE/g dry
      matter, respectively.

PMID- 27884877
TI  - Associations between Measures of Structural Morphometry and Sensorimotor
      Performance in Individuals with Nonspecific Low Back Pain.
AB  - BACKGROUND AND PURPOSE: To date, most structural brain imaging studies in
      individuals with nonspecific low back pain have evaluated volumetric changes.
      These alterations are particularly found in sensorimotor-related areas. Although
      it is suggested that specific measures, such as cortical surface area and
      cortical thickness, reflect different underlying neural architectures, the
      literature regarding these different measures in individuals with nonspecific low
      back pain is limited. Therefore, the current study was designed to investigate
      the association between the performance on a sensorimotor task, more specifically
      the sit-to-stand-to-sit task, and cortical surface area and cortical thickness in
      individuals with nonspecific low back pain and healthy controls. MATERIALS AND
      METHODS: Seventeen individuals with nonspecific low back pain and 17 healthy
      controls were instructed to perform 5 consecutive sit-to-stand-to-sit movements
      as fast as possible. In addition, T1-weighted anatomic scans of the brain were
      acquired and analyzed with FreeSurfer. RESULTS: Compared with healthy controls,
      individuals with nonspecific low back pain needed significantly more time to
      perform 5 sit-to-stand-to-sit movements (P < .05). Brain morphometric analyses
      revealed that cortical thickness of the ventrolateral prefrontal cortical regions
      was increased in patients with nonspecific low back pain compared with controls.
      Furthermore, decreased cortical thickness of the rostral anterior cingulate
      cortex was associated with lower sit-to-stand-to-sit performance on an unstable
      support surface in individuals with nonspecific low back pain and healthy
      controls (r = -0.47, P < .007). In addition, a positive correlation was found
      between perceived pain intensity and cortical thickness of the superior frontal
      gyrus (r = 0.70, P < .002) and the pars opercularis of the inferior ventrolateral
      prefrontal cortex (r = 0.67, P < .004). Hence, increased cortical thickness was
      associated with increased levels of pain intensity in individuals with
      nonspecific low back pain. No associations were found between cortical surface
      area and the pain characteristics in this group. CONCLUSIONS: The current study
      suggests that cortical thickness may contribute to different aspects of sit-to
      stand-to-sit performance and perceived pain intensity in individuals with
      nonspecific low back pain.

PMID- 27884879
TI  - Henry J.M. Barnett.

PMID- 27884878
TI  - Comparison of 3 Different Types of Spinal Arteriovenous Shunts below the Conus in
      Clinical Presentation, Radiologic Findings, and Outcomes.
AB  - BACKGROUND AND PURPOSE: Spinal arteriovenous shunts below the conus constitute 3
      types of lesions, which have previously been mainly described in case reports,
      given their rarity, and are sometimes misdiagnosed. The purpose of this study was
      to describe the features of each type and compare these types as to epidemiologic
      features, clinical and radiologic presentations, treatment, and outcomes in a
      consecutive series of 48 cases. MATERIALS AND METHODS: The prospectively
      collected data bases of 2 referral centers for spinal vascular lesions were
      retrospectively reviewed. Spinal arteriovenous shunts below the conus were
      defined as all dural and intradural shunts below the conus medullaris. Clinical
      features, radiologic findings, treatment results, and clinical outcomes were
      assessed. RESULTS: There were filum terminale arteriovenous fistulas in 11
      patients (22.9%), radicular arteriovenous shunts in 7 patients (14.6%), and
      spinal dural arteriovenous fistulas in 30 patients (62.5%). Radicular
      arteriovenous shunts presented at a younger age (P = .017) and with a higher
      incidence of back pain symptoms (P = .037). A tethered spinal cord was found in
      54.5% of patients with filum terminale arteriovenous fistulas and 23.3% of
      patients with spinal dural arteriovenous fistulas. After treatment, the
      angiographic complete obliteration rate was 89.4% and spinal function was
      improved significantly (P < .001). CONCLUSIONS: Three groups of spinal
      arteriovenous shunts below the conus can be differentiated according to clinical
      and radiologic features. Filum terminale arteriovenous fistulas are frequently
      associated with dysraphic malformations, which may suggest a particular
      embryologic origin.

PMID- 27884880
TI  - First-Pass Contrast-Enhanced MRA for Pretherapeutic Diagnosis of Spinal Epidural
      Arteriovenous Fistulas with Intradural Venous Reflux.
AB  - BACKGROUND AND PURPOSE: Spinal epidural AVFs are rare spinal vascular
      malformations. When there is associated intradural venous reflux, they may mimic
      the more common spinal dural AVFs. Correct diagnosis and localization before
      conventional angiography is beneficial to facilitate treatment. We hypothesize
      that first-pass contrast-enhanced MRA can diagnose and localize spinal epidural
      AVFs with intradural venous reflux and distinguish them from other spinal AVFs.
      MATERIALS AND METHODS: Forty-two consecutive patients with a clinical and/or
      radiologic suspicion of spinal AVF underwent MR imaging, first-pass contrast
      enhanced MRA, and DSA at a single institute (2000-2015). MR imaging/MRA and DSA
      studies were reviewed by 2 independent blinded observers. DSA was used as the
      reference standard. RESULTS: On MRA, all 7 spinal epidural AVFs with intradural
      venous reflux were correctly diagnosed and localized with no interobserver
      disagreement. The key diagnostic feature was arterialized filling of an epidural
      venous pouch with a refluxing radicular vein arising from the arterialized
      epidural venous system. CONCLUSIONS: First-pass contrast-enhanced MRA is a
      reliable and useful technique for the initial diagnosis and localization of
      spinal epidural AVFs with intradural venous reflux and can distinguish these
      lesions from other spinal AVFs.

PMID- 27884882
TI  - Lymphomatosis cerebri: diagnostic challenges and review of the literature.
AB  - Lymphomatosis cerebri (LC) is a rare variant of a primary central nervous system
      non-Hodgkin's lymphoma (PCNSL) characterised by diffuse infiltration of tumour
      cells throughout the brain parenchyma. We present a 68-year-old immunocompetent
      woman with headaches, dizziness, blurred vision, localised right leg weakness and
      rapidly progressive dementia. A brain MRI demonstrated diffuse T2 hyperintense
      white matter lesions that did not enhance with contrast. The clinical
      differential diagnosis of these lesions included metastatic disease, infectious
      or inflammatory process such as sarcoidosis, lymphoma, demyelinating disease and
      less likely vascular aetiology, such as vasculitis or ischaemic stroke. A right
      frontal stereotactic brain biopsy was non-diagnostic. The patient eventually died
      from aspiration pneumonia following a pneumonectomy for a primary lung
      adenocarcinoma. The diagnosis of LC was established on postmortem examination of
      the brain.

PMID- 27884881
TI  - Testing Stenting and Flow Diversion Using a Surgical Elastase-Induced Complex
      Fusiform Aneurysm Model.
AB  - BACKGROUND AND PURPOSE: Rabbit elastase-induced saccular aneurysms have been
      commonly used for preclinical testing of endovascular devices, including flow
      diverters. However, all tested devices have been shown to be capable of aneurysm
      occlusion with this model. We aimed to create a more challenging model to test
      and discriminate among neurovascular devices of varying efficacies. MATERIALS AND
      METHODS: With a surgical approach that included elastase infusion and balloon
      dilation, we attempted the creation of complex fusiform aneurysms in 16 rabbits,
      with standard saccular carotid aneurysms created in 15 other animals. Aneurysms
      were randomly allocated to one of the following treatments: flow diversion (n =
      8), high-porosity stent (n = 6), double high-porosity stent (n = 5), and control
      (n = 6). Angiographic assessment and pathologic analyses were performed at 3
      months. RESULTS: Creation of complex fusiform and standard saccular aneurysms was
      successful in 12/16 and 13/15 attempts, respectively. All saccular (n = 4) or
      complex fusiform (n = 4) aneurysms treated with flow diverters were successfully
      occluded. Three of 3 saccular compared with 0/2 complex fusiform aneurysms were
      occluded by double high-porosity stents. One of 3 saccular and 0/3 complex
      fusiform aneurysms were occluded by a single high-porosity stent. Both aneurysm
      types shared the same pathologic findings when untreated: The aneurysm wall
      lacked an elastic layer and smooth muscle cells, while the lumen was lined with
      neointima of varying thickness. Neointimal coverage of the devices was complete
      when aneurysms were occluded, while leaks were always associated with aneurysm
      remnants. CONCLUSIONS: Challenging fusiform aneurysms can be created in rabbits
      by using a surgical modification of the elastase method.

PMID- 27884883
TI  - Bilateral ureteric obstruction during in vitro fertilisation therapy in a patient
      with complex surgically managed Crohn's disease.
AB  - A 37-year-old woman receiving in vitro fertilisation (IVF) treatment presented
      with lethargy, fevers and anuria. Her background included complex surgically
      managed Crohn's disease and mild right-sided hydronephrosis (with no evidence of
      obstruction on MAG3 renogram). On examination, she had a distended abdomen with
      generalised tenderness. Blood tests revealed an acute kidney injury and confirmed
      sepsis. She was found to have bilateral ureteric obstruction with worsening of
      the right-sided hydronephrosis and new-onset left-sided hydronephrosis secondary
      to bilateral ovarian masses, diagnosed as mild ovarian hyperstimulation syndrome
      (OHSS). She was initially managed with fluid resuscitation, bilateral
      nephrostomies, antibiotics and supportive management of mild OHSS. She made a
      good recovery and was discharged after placement of antegrade stents and removal
      of nephrostomies. On follow-up, following resolution of ovarian hyperstimulation,
      she has been diagnosed with a right-sided distal ureteric stricture and is
      awaiting reconstruction. Her left ureteric stent has been removed.

PMID- 27884884
TI  - Existing evidence is insufficient to justify metformin or other agents as first
      line therapy for type 2 diabetes.

PMID- 27884885
TI  - Rate of epilepsy in people with autism and the rate of autism in people with
      epilepsy are high.

PMID- 27884886
TI  - A question of evidence.

PMID- 27884887
TI  - Number of locums has doubled since 2009.

PMID- 27884888
TI  - Getting the Message Out.

PMID- 27884889
TI  - Palliative care in children with cancer: implications for general practice.

PMID- 27884890
TI  - New technologies and general practice.

PMID- 27884891
TI  - BJGP Open: a new, online-only, open access journal.

PMID- 27884892
TI  - GPFV: a new charter for general practice?

PMID- 27884893
TI  - Primary care is the cornerstone of our NHS.

PMID- 27884894
TI  - Confronting the bashing: fundamental questions remain.

PMID- 27884895
TI  - Bullying and banter.

PMID- 27884896
TI  - Colchicine in overdose.

PMID- 27884897
TI  - Child health training and the College.

PMID- 27884898
TI  - Cruse Bereavement Care.

PMID- 27884899
TI  - Family medicine on the rise in Kosovo.

PMID- 27884900
TI  - Shoot the academics? Running the gauntlet of online responders.

PMID- 27884901
TI  - The reappearance of the sick man: a landmark publication revisited.

PMID- 27884902
TI  - La Tour's hypovitaminosis in the peasants' swollen eyelids and deformed nails.

PMID- 27884903
TI  - Yonder: European GP workforce, asthma, malignant wounds, and breast implants.

PMID- 27884904
TI  - RCGP Research Paper of the Year 2015: strong messages for clinical care in all
      six research categories.

PMID- 27884905
TI  - Bad Medicine: Resilience.

PMID- 27884906
TI  - Our ailing profession: we need more than resilience and replenishment.

PMID- 27884907
TI  - Books: A Body of Work: An Anthology of Poetry and Medicine: A Body Beautiful.

PMID- 27884908
TI  - Books: The FRAYED Consultation Model for Doctors Dealing with Unreasonable
      Demands from Difficult Patients: A Communication Skills Guide for Stressed GPs on
      How to Survive Doctor-Patient Conflict: To Yield or not to Yield.

PMID- 27884909
TI  - BJGP Library: Howards End.

PMID- 27884910
TI  - In praise of the vanishing skill of watchful waiting.

PMID- 27884911
TI  - Time to rethink the capture and use of family history in primary care.

PMID- 27884912
TI  - Peer review: acknowledging its value and recognising the reviewers.

PMID- 27884913
TI  - Reducing the risk of type 2 diabetes mellitus in primary care after gestational
      diabetes: a role for mobile technology to improve current care.

PMID- 27884914
TI  - Red eyes in children: red flags and a case to learn from.

PMID- 27884915
TI  - A case of congenital rubella syndrome and infection in South-East London in 2015:
      prevention, diagnosis, and the public health response.

PMID- 27884916
TI  - Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual
      bleeding: long-term randomised pragmatic trial in primary care.
AB  - BACKGROUND: Heavy menstrual bleeding (HMB) is a common, chronic problem affecting
      women and health services. However, long-term evidence on treatment in primary
      care is lacking. AIM: To assess the effectiveness of commencing the
      levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical
      treatments for women presenting with HMB in general practice. DESIGN AND SETTING:
      A pragmatic, multicentre, parallel, open-label, long term, randomised controlled
      trial in 63 primary care practices across the English Midlands. METHOD: In total,
      571 women aged 25-50 years, with HMB were randomised to LNG-IUS or usual medical
      treatment (tranexamic/mefenamic acid, combined oestrogen-progestogen, or
      progesterone alone). The primary outcome was the patient reported Menorrhagia
      Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties,
      social life, psychological and physical health, and work and family life; scores
      from 0 to 100). Secondary outcomes included surgical intervention (endometrial
      ablation/hysterectomy), general quality of life, sexual activity, and safety.
      RESULTS: At 5 years post-randomisation, 424 (74%) women provided data. While the
      difference between LNG-IUS and usual treatment groups was not significant (3.9
      points; 95% confidence interval = -0.6 to 8.3; P = 0.09), MMAS scores improved
      significantly in both groups from baseline (mean increase, 44.9 and 43.4 points,
      respectively; P<0.001 for both comparisons). Rates of surgical intervention were
      low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95%
      CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life,
      sexual activity scores, or serious adverse events. CONCLUSION: Large improvements
      in symptom relief across both groups show treatment for HMB can be successfully
      initiated with long-term benefit and with only modest need for surgery.

PMID- 27884917
TI  - Managing barriers to empathy in the clinical encounter: a qualitative interview
      study with GPs.
AB  - BACKGROUND: Current daily general practice has become increasingly technical and
      somatically oriented (where attention to patients' feelings is decreased) due to
      an increase in protocol-based guidelines. Priorities in GP-patient communication
      have shifted from a focus on listening and empathy to task-oriented
      communication. AIM: To explore what barriers GPs experience when applying empathy
      in daily practice, and how these barriers are managed. DESIGN AND SETTING: Thirty
      Dutch GPs with sufficient heterogeneity in sex, age, type of practice, and rural
      or urban setting were interviewed. METHOD: The consolidated criteria for
      reporting qualitative research (COREQ) were applied. The verbatim transcripts
      were then analysed. RESULTS: According to participating GPs, the current emphasis
      on protocol-driven care can be a significant barrier to genuineness in
      communication. Other potential barriers mentioned were time pressures and
      constraints, and dealing with patients displaying 'unruly behaviour' or those
      with personality disorders. GPs indicated that it can be difficult to balance
      emotional involvement and professional distance. Longer consulting times, smaller
      practice populations, and efficient practice organisation were described as
      practical solutions. In order to focus on a patient-as-person approach, GPs
      strongly suggested that deviating from guidelines should be possible when
      necessary as an element of good-quality care. Joining intercollegiate counselling
      groups was also discussed. CONCLUSION: In addition to practical solutions for
      barriers to behaving empathically, GPs indicated that they needed more freedom to
      balance working with protocols and guidelines, as well as a patient-as-person and
      patient-as-partner approach. This balance is necessary to remain connected with
      patients and to deliver care that is truly personal.

PMID- 27884918
TI  - Patients' beliefs on the impediments to good diabetes control: a mixed methods
      study of patients in general practice.
AB  - BACKGROUND: Most people with diabetes are not attaining desirable levels of HbA1c
      (glycated haemoglobin), or of blood pressure and cholesterol, leaving them at
      risk of developing complications. AIM: To identify ways of improving diabetes
      control by gaining insight into patients' attitudes/beliefs. DESIGN AND SETTING:
      Questionnaires were offered to patients attending for a diabetes review in the 24
      GP practices of North East Hampshire and Farnham Clinical Commissioning Group.
      METHOD: Infrequent attenders were contacted by post. Volunteers then participated
      in focus groups. RESULTS: Self-reported medication adherence was good with 83%
      (98/118) of responders recording >=9 on a 10-point scale. Patients generally
      accepted they 'needed' and 'could take' medication. A substantial minority
      reported 'not liking' taking tablets. Focus groups confirmed this and revealed a
      reluctance to change lifestyle, with medication reported as a way to evade it. A
      total of 68 out of 112 responders (60.7%) knew their HbA1c value. However, focus
      groups identified little understanding of HbA1c, with responders perceiving it as
      medical jargon. Phrases such as 'stuck-on-sugar' or 'sugarload' were suggested as
      being semantically easier to understand. The questionnaire revealed trust in
      clinicians. This was confirmed in focus groups but confounded by frequent reports
      of healthcare providers giving inadequate/incorrect advice. CONCLUSION:
      Investment in lifestyle change is needed. Participants were reluctant to change
      and saw medication as a way of avoiding it. HbA1c needs to be better explained.
      Intuitive phrases such as 'stuck-on-sugar' or 'sugarload' could be adopted into
      common parlance. Inadequate/incorrect advice seems to be hampering diabetes
      management and there appears to be a need for more diabetes-trained clinicians.

PMID- 27884919
TI  - Percutaneous cooled-probe microwave versus radiofrequency ablation in early-stage
      hepatocellular carcinoma: a phase III randomised controlled trial.

PMID- 27884920
TI  - Systematic review of bariatric surgery liver biopsies clarifies the natural
      history of liver disease in patients with severe obesity.
AB  - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a frequent complication
      of morbid obesity, but its severity varies greatly and thus there is a strong
      need to better define its natural history in these patients. DESIGN: Liver
      biopsies were systematically performed in 798 consecutive patients with severe
      obesity undergoing bariatric surgery. Histology was compared with clinical,
      biological, anthropometrical and body composition characteristics. RESULTS:
      Patients with presumably normal liver (n=179, 22%) were significantly younger at
      bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001).
      However, both groups showed quite similar obesity duration, since patients with
      presumably normal liver reported the onset of obesity at a significantly younger
      age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass
      ratio increased according to liver disease severity (presumably normal liver:
      1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001),
      although the total body fat mass decreased (presumably normal liver: 50%,
      steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes
      increased according to severity of liver disease but only in female patients
      (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996
      picolitres). CONCLUSIONS: These results suggest that young adults are more prone
      to store fat in subcutaneous tissue and reach the threshold of bariatric surgery
      indication before their liver is damaged. A shift of fat storage from
      subcutaneous to visceral adipose tissue compartment is associated with liver
      damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in
      females since hypertrophic adipocytes are more exposed to lipolysis and to the
      production of inflammatory mediators.

PMID- 27884921
TI  - Reply: 'More viral mutants, less HBsAg clearance? One size may not fit all'.

PMID- 27884922
TI  - Letter to editor: Best estimations of the effects of alcohol on emergency
      department attendance.

PMID- 27884923
TI  - Clinical metrics in emergency medicine: the shock index and the probability of
      hospital admission and inpatient mortality.
AB  - STUDY OBJECTIVES: The shock index (SI), defined as the ratio of HR to systolic
      BP, has been studied as an alternative prognostic tool to traditional vital signs
      in specific disease states and subgroups of patients. However, literature
      regarding its utility in the general ED population is lacking. Our main objective
      was to determine the probability of admission and inpatient mortality based on
      the first measured SI at initial presentation in the general adult ED population
      in our tertiary care centre. METHODS: A retrospective chart review of all adult
      patients (>=18 years old) presenting to the ED at our tertiary care centre over a
      12-month period was conducted. Likelihood ratios (LRs) were calculated in order
      to determine the optimal SI cut-off for predicting hospital admission and
      inpatient mortality. RESULTS: We reviewed 58 336 ED patient encounters occurring
      between 1 October 2012 and 30 September 2013. SI >1.2 was associated with a large
      increase in the likelihood of hospital admission, with a positive LR (+LR) of
      11.69 (95% CI 9.50 to 14.39) and a moderate increase in the likelihood of
      inpatient mortality with a +LR of 5.82 (95% CI 4.31 to 7.85). SI >0.7 and >0.9,
      the traditional 'normal' cut-offs cited in the literature, were only associated
      with minimal to small increases in the likelihood of admission and inpatient
      mortality. CONCLUSIONS: In our single-centre study, the initial SI recorded in
      the ED shows promise as a clinical metric in the general adult ED population,
      increasing the probability of both hospital admission and inpatient mortality,
      specifically at a threshold of SI >1.2.

PMID- 27884926
TI  - Proposal for an improved classification system for cavernous sinus dural
      arteriovenous fistula (CS-DAVF).

PMID- 27884927
TI  - Novel approaches to access and treatment of cavernous sinus dural arteriovenous
      fistula (CS-DAVF): case series and review of the literature.
AB  - Caroticocavernous fistula or cavernous sinus dural arteriovenous fistula (CS
      DAVF) has presented various treatment challenges over many years. This paper
      outlines these challenges in a review of the literature, and attempts to address
      them by analyzing the anatomical and hemodynamic characteristics of 32
      consecutive patients with CS-DAVF treated between 2007 and 2016, in doing so
      proposing novel strategies for safe access and treatment of CS-DAVF.

PMID- 27884924
TI  - Low-acuity presentations to the emergency department in Canada: exploring the
      alternative attempts to avoid presentation.
AB  - OBJECTIVE: ED visits have been rising year on year worldwide. It has been
      suggested that some of these visits could be avoided if low-acuity patients had
      better primary care access. This study explored patients' efforts to avoid ED
      presentation and alternative care sought prior to presentation. METHODS:
      Consecutive adult patients presenting to three urban EDs in Edmonton, Canada,
      completed a questionnaire collecting demographics, actions attempted to avoid
      presentation and reasons for presentation. Survey data were cross-referenced to a
      minimal patient dataset containing ED and demographic information. RESULTS: A
      total of 1402 patients (66.5%) completed the survey. Although 89.3% of the
      patients felt that the ED was their best care option, the majority of patients
      (60.1%) sought alternative care or advice prior to presentation. Men, individuals
      who presented with injury only, and individuals with less than a high school
      education were all less likely to seek alternative care. Alternative care actions
      included visiting a physician (54.1%) or an alternative healthcare professional
      (eg, chiropractor, physiotherapist, etc; 21.2%), calling physician offices (47%)
      or the regional health information line (13%). Of those who called their
      physicians, the majority received advice to present to the ED (67.5%).
      CONCLUSIONS: Most low-acuity patients attempt to avoid ED presentation by seeking
      alternative care. This analysis identifies groups of individuals in the study
      region who are less likely to seek alternative care first and may benefit from
      targeted interventions/education. Other regions may wish to complete a similar
      profile to determine which patients are less likely to seek alternative care
      first.

PMID- 27884928
TI  - MACRA 2.0: are you ready for MIPS?
AB  - The annual cost of healthcare delivery in the USA now exceeds US$3 trillion. Fee
      for service methodology is often implicated as a cause of this exceedingly high
      figure. The Affordable Care Act created the Center for Medicare and Medicaid
      Innovation (CMMI) to pilot test value based alternative payments for reimbursing
      physician services. In 2015, the Medicare Access and CHIP Reauthorization Act
      (MACRA) was passed into law. MACRA has dramatic implications for all US based
      healthcare providers. MACRA permanently repealed the Medicare Sustainable Growth
      Rate so as to stabilize physician part B Medicare payments, consolidated pre
      existing federal performance programs into the Merit based Incentive Payments
      System (MIPS), and legislatively mandated new approaches to paying clinicians.
      Neurointerventionalists will predominantly participate in MIPS. MIPS unifies,
      updates, and streamlines previously existing federal performance programs,
      thereby reducing onerous redundancies and overall administrative burden, while
      consolidating performance based payment adjustments. While MIPS may be perceived
      as a straightforward continuation of fee for service methodology with performance
      modifiers, MIPS is better viewed as a stepping stone toward eventually adopting
      alternative payment models in later years. In October 2016, the Centers for
      Medicare and Medicaid Services (CMS) released a final rule for MACRA
      implementation, providing greater clarity regarding 2017 requirements. The final
      rule provides a range of options for easing MIPS reporting requirements in the
      first performance year. Nonetheless, taking the newly offered 'minimum possible'
      approach toward meeting the requirements will still have negative consequences
      for providers.

PMID- 27884929
TI  - Pro-nociceptive migraine mediator CGRP provides neuroprotection of sensory,
      cortical and cerebellar neurons via multi-kinase signaling.
AB  - Background Blocking the pro-nociceptive action of CGRP is one of the most
      promising approaches for migraine prophylaxis. The aim of this study was to
      explore a role for CGRP as a neuroprotective agent for central and peripheral
      neurons. Methods The viability of isolated rat trigeminal, cortical and
      cerebellar neurons was tested by fluorescence vital assay. Engagement of Nrf2
      target genes was analyzed by qPCR. The neuroprotective efficacy of CGRP in vivo
      was tested in mice using a permanent cerebral ischemia model. Results CGRP
      prevented apoptosis induced by the amino acid homocysteine in all three distinct
      neuronal populations. Using a set of specific kinase inhibitors, we show the role
      of multi-kinase signaling pathways involving PKA and CaMKII in neuronal survival.
      Forskolin triggered a very similar signaling cascade, suggesting that cAMP is the
      main upstream trigger for multi-kinase neuroprotection. The specific CGRP
      antagonist BIBN4096 reduced cellular viability, lending further support to the
      proposed neuroprotective function of CGRP. Importantly, CGRP was neuroprotective
      against permanent ischemia in mice. Conclusion Our data show an unexpected
      'positive' role for the endogenous pro-nociceptive migraine mediator CGRP,
      suggesting more careful examination of migraine prophylaxis strategy based on
      CGRP antagonism although it should be noted that homocysteine induced apoptosis
      in primary neuronal cell culture might not necessarily reproduce all the features
      of cell loss in the living organism.

PMID- 27884930
TI  - Diet modification challenges faced by marginalized and nonmarginalized adults
      with type 2 diabetes: A systematic review and qualitative meta-synthesis.
AB  - Objectives Diet modification is an important part of the prevention and treatment
      of type 2 diabetes, but sustained dietary change remains elusive for many
      individuals. This paper describes and interprets the barriers to diet
      modification from the perspective of people with type 2 diabetes, paying
      particular attention to the experiences of people who experience social
      marginalization. Methods A systematic review of primary, empirical qualitative
      research was performed, capturing 120 relevant studies published between 2002 and
      2015. Qualitative meta-synthesis was used to provide an integrative analysis of
      this knowledge. Results Due to the central role of food in social life, dietary
      change affects all aspects of a person's life, and barriers related to self
      discipline, emotions, family and social support, social significance of food, and
      knowledge were identified. These barriers are inter-linked and overlapping.
      Social marginalization magnifies barriers; people who face social marginalization
      are trying to make the same changes as other people with diabetes with fewer
      socio-material resources in the face of greater challenges. Discussion A social
      ecological model of behavior supports our findings of challenges at all levels,
      and highlights the need for interventions and counseling strategies that address
      the social and environmental factors that shape and sustain dietary change.

PMID- 27884933
TI  - Using the Personality Assessment Inventory Antisocial and Borderline Features
      Scales to Predict Behavior Change: A Multisite Longitudinal Study of Youthful
      Offenders.
AB  - A substantial amount of research has examined the developmental trajectory of
      antisocial behavior and, in particular, the relationship between antisocial
      behavior and maladaptive personality traits. However, research typically has not
      controlled for previous behavior (e.g., past violence) when examining the utility
      of personality measures, such as self-report scales of antisocial and borderline
      traits, in predicting future behavior (e.g., subsequent violence). Examination of
      the potential interactive effects of measures of both antisocial and borderline
      traits also is relatively rare in longitudinal research predicting adverse
      outcomes. The current study utilizes a large sample of youthful offenders ( N =
      1,354) from the Pathways to Desistance project to examine the separate effects of
      the Personality Assessment Inventory Antisocial Features (ANT) and Borderline
      Features (BOR) scales in predicting future offending behavior as well as trends
      in other negative outcomes (e.g., substance abuse, violence, employment
      difficulties) over a 1-year follow-up period. In addition, an ANT * BOR
      interaction term was created to explore the predictive effects of secondary
      psychopathy. ANT and BOR both explained unique variance in the prediction of
      various negative outcomes even after controlling for past indicators of those
      same behaviors during the preceding year.

PMID- 27884931
TI  - Mild Depressive Symptoms Mediate the Impact of Childhood Trauma on Long-Term
      Functional Outcome in Early Psychosis Patients.
AB  - Introduction: The mechanism linking childhood trauma (CT) to the functional
      deficits observed in early psychosis (EP) patients is as yet unknown. We aim to
      examine the potential mediating effect of depressive symptoms in this well
      established association. Methods: Two hundred nine EP subjects aged 18-35 were
      assessed for functioning and psychopathology after 2, 6, 12, 18, 24, 30, and 36
      months of treatment. Patients were classified into early trauma if they had faced
      at least one experience of abuse (physical, sexual, or emotional) or neglect
      (physical or emotional) before age 12, and late trauma if the exposure had
      occurred between ages 12 and 16. Diagnosis was based on the criteria of the
      Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).
      Psychopathology was assessed with the Positive and Negative Syndrome Scale and
      the Montgomery-Asberg Depression Rating Scale. Functioning was measured with the
      Global Assessment of Functioning (GAF) and the Social and Occupational
      Functioning Assessment Scale (SOFAS). Mediation analyses were performed in order
      to study whether the relationship between CT and functioning was mediated by
      depressive symptoms. Results: When compared with nonexposed patients, early but
      not late trauma patients showed lower levels of GAF and SOFAS scores over all the
      time points, excepting after the first assessment. After 30 and 36 months, the
      effect of early trauma on functioning was completely mediated by depressive
      symptoms. No mediating effect of positive or negative symptoms was highlighted at
      those time points. Conclusion: Mild depressive symptoms mediated the impact of
      early trauma on long-term functional outcome. Intensifying pharmacologic and/or
      psychotherapeutic treatment, focused on the depressive dimension, may help
      traumatized EP patients to improve their functioning.

PMID- 27884932
TI  - Drosophila WASH is required for integrin-mediated cell adhesion, cell motility
      and lysosomal neutralization.
AB  - The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH; also known as
      Washout in flies) is a conserved actin-nucleation-promoting factor controlling
      Arp2/3 complex activity in endosomal sorting and recycling. Previous studies have
      identified WASH as an essential regulator in Drosophila development. Here, we
      show that homozygous wash mutant flies are viable and fertile. We demonstrate
      that Drosophila WASH has conserved functions in integrin receptor recycling and
      lysosome neutralization. WASH generates actin patches on endosomes and lysosomes,
      thereby mediating both aforementioned functions. Consistently, loss of WASH
      function results in cell spreading and cell migration defects of macrophages, and
      an increased lysosomal acidification that affects efficient phagocytic and
      autophagic clearance. WASH physically interacts with the vacuolar (V)-ATPase
      subunit Vha55 that is crucial to establish and maintain lysosome acidification.
      As a consequence, starved flies that lack WASH function show a dramatic increase
      in acidic autolysosomes, causing a reduced lifespan. Thus, our data highlight a
      conserved role for WASH in the endocytic sorting and recycling of membrane
      proteins, such as integrins and the V-ATPase, that increase the likelihood of
      survival under nutrient deprivation.

PMID- 27884934
TI  - Chronic neuropathic pain severity is determined by lesion level in aquaporin 4
      antibody-positive myelitis.
AB  - IMPORTANCE: Chronic, intractable neuropathic pain is a common and debilitating
      consequence of neuromyelitis optica spectrum disorder (NMOSD) myelitis, with no
      satisfactory treatment; few studies have yet to explore its aetiology. OBJECTIVE:
      To establish if myelitis-associated chronic pain in NMOSD is related to the
      craniocaudal location of spinal cord lesions. METHOD: (1) Retrospective cohort of
      76 aquaporin 4-antibody (AQP4-Ab)-positive patients from Oxford and Liverpool's
      national NMOSD clinics, assessing current pain and craniocaudal location of cord
      lesion contemporary to pain onset. (2) Focused prospective study of 26 AQP4-Ab
      positive Oxford patients, a subset of the retrospective cohort, assessing current
      craniocaudal lesion location and current pain. RESULTS: Patients with isolated
      thoracic cord myelitis at the time of pain onset were significantly more disabled
      and suffered more pain. Cervical and thoracic lesions that persisted from pain
      onset to 'out of relapse' follow-up (current MRI) had highly significant (p<0.01)
      opposing effects on pain scores (std. beta=-0.46 and 0.48, respectively). Lesion
      length, total lesion burden and number of transverse myelitis relapses did not
      correlate with pain. CONCLUSIONS: Persistent, caudally located (ie, thoracic)
      cord lesions in AQP4-Ab-positive patients associate with high postmyelitis
      chronic pain scores, irrespective of number of myelitis relapses, lesion length
      and lesion burden. Although disability correlated with pain in isolation, it
      became an insignificant predictor of pain when analysed alongside craniocaudal
      location of lesions.

PMID- 27884937
TI  - Implementation of ICRP 116 Dose Conversion Coefficients for Reconstructing Organ
      Dose in a Radiation Compensation Program.
AB  - Since 2000, National Institute for Occupational Safety and Health (NIOSH) has
      used dose conversion coefficients published by the International Commission on
      Radiation Protection in report 74 (ICRP 74) to determine organ dose from external
      radiation sources. In 2010, the ICRP issued publication 116 using more realistic
      phantoms than ICRP 74. NIOSH has developed a Monte Carlo method to sample the
      energy-organ-specific distribution of the ICRP 116 conversion coefficients to
      determine the organ dose and the associated uncertainty. Using Monte Carlo
      methods, irradiation geometry factors (IGFs) were developed to convert the
      measured dosemeter dose on the front of the body to values that are compatible
      with ICRP 116 organ dose conversion coefficients. Specific IGFs were developed
      for (1) both neutrons and photon exposures, (2) to male and female workers and
      (3) for rotational and isotropic exposure geometries. The computed mean organ
      dose and the associated uncertainty are used in the probability of causation
      calculation for compensation.

PMID- 27884936
TI  - CONSTANCES: a general prospective population-based cohort for occupational and
      environmental epidemiology: cohort profile.
AB  - : WHY THE COHORT WAS SET UP?: CONSTANCES is a general-purpose cohort with a focus
      on occupational and environmental factors. COHORT PARTICIPANTS: CONSTANCES was
      designed as a randomly selected sample of French adults aged 18-69 years at
      inception; 200 000 participants will be included. DATA COLLECTION PHASES: At
      enrolment, the participants are invited to complete questionnaires and to attend
      a health screening centre (HSC) for a health examination. A biobank will be set
      up. The follow-up includes an yearly self-administered questionnaire, a periodic
      visit to an HSC and linkage to social and national health administrative
      databases. MAIN TYPES OF DATA COLLECTED: Data collected for participants include
      social and demographic characteristics, socioeconomic status, life events and
      behaviours. Regarding occupational and environmental factors, a wealth of data on
      organisational, chemical, biological, biomechanical and psychosocial lifelong
      exposure, as well as residential characteristics, are collected at enrolment and
      during follow-up. The health data cover a wide spectrum: self-reported health
      scales, reported prevalent and incident diseases, long-term chronic diseases and
      hospitalisations, sick-leaves, handicaps, limitations, disabilities and injuries,
      healthcare usage and services provided, and causes of death. CONTROL OF SELECTION
      EFFECTS: To take into account non-participation and attrition, a random cohort of
      non-participants was set up and will be followed through the same national
      databases as participants. DATA ACCESS: Inclusions begun at the end of 2012 and
      more than 110 000 participants were already included by September 2016. Several
      projects on occupational and environmental risks already applied to a public call
      for nested research projects.

PMID- 27884935
TI  - Diagnostic value of exome and whole genome sequencing in craniosynostosis.
AB  - BACKGROUND: Craniosynostosis, the premature fusion of one or more cranial
      sutures, occurs in ~1 in 2250 births, either in isolation or as part of a
      syndrome. Mutations in at least 57 genes have been associated with
      craniosynostosis, but only a minority of these are included in routine laboratory
      genetic testing. METHODS: We used exome or whole genome sequencing to seek a
      genetic cause in a cohort of 40 subjects with craniosynostosis, selected by
      clinical or molecular geneticists as being high-priority cases, and in whom prior
      clinically driven genetic testing had been negative. RESULTS: We identified
      likely associated mutations in 15 patients (37.5%), involving 14 different genes.
      All genes were mutated in single families, except for IL11RA (two families). We
      classified the other positive diagnoses as follows: commonly mutated
      craniosynostosis genes with atypical presentation (EFNB1, TWIST1); other core
      craniosynostosis genes (CDC45, MSX2, ZIC1); genes for which mutations are only
      rarely associated with craniosynostosis (FBN1, HUWE1, KRAS, STAT3); and known
      disease genes for which a causal relationship with craniosynostosis is currently
      unknown (AHDC1, NTRK2). In two further families, likely novel disease genes are
      currently undergoing functional validation. In 5 of the 15 positive cases, the
      (previously unanticipated) molecular diagnosis had immediate, actionable
      consequences for either genetic or medical management (mutations in EFNB1, FBN1,
      KRAS, NTRK2, STAT3). CONCLUSIONS: This substantial genetic heterogeneity, and the
      multiple actionable mutations identified, emphasises the benefits of exome/whole
      genome sequencing to identify causal mutations in craniosynostosis cases for
      which routine clinical testing has yielded negative results.

PMID- 27884938
TI  - The Russian Human Radiobiological Tissue Repository: A Unique Resource for
      Studies of Plutonium-Exposed Workers.
AB  - The Russian Radiobiological Human Tissue Repository (RHTR) at the Southern Urals
      Biophysics Institute in Ozyorsk, Russia, was established to collect and store
      biospecimens supporting research on health consequences of chronic, low-dose
      radiation exposures. The purpose of this paper is to describe the RHTR resources
      and the availability of high-quality biological specimens. RHTR has enrolled two
      groups of subjects from 1951 to the present time: exposed workers at the Mayak
      Production Association facilities and residents of Ozyorsk who were never
      occupationally exposed to ionizing radiation (controls). Biospecimens are
      collected with informed consent of participants and are annotated with
      demographic, occupational, dosimetry and medical information. To date, 900
      individuals have provided surgical tissues and 1000 have provided autopsy
      tissues. Blood samples are also collected and stored. Familial DNA is available
      from parent-offspring triads. Biospecimens and annotated data are available to
      interested scientists worldwide, via the RHTR website.

PMID- 27884939
TI  - Regulation of sugar transporter activity for antibacterial defense in
      Arabidopsis.
AB  - Microbial pathogens strategically acquire metabolites from their hosts during
      infection. Here we show that the host can intervene to prevent such metabolite
      loss to pathogens. Phosphorylation-dependent regulation of sugar transport
      protein 13 (STP13) is required for antibacterial defense in the plant Arabidopsis
      thaliana STP13 physically associates with the flagellin receptor flagellin
      sensitive 2 (FLS2) and its co-receptor BRASSINOSTEROID INSENSITIVE 1-associated
      receptor kinase 1 (BAK1). BAK1 phosphorylates STP13 at threonine 485, which
      enhances its monosaccharide uptake activity to compete with bacteria for
      extracellular sugars. Limiting the availability of extracellular sugar deprives
      bacteria of an energy source and restricts virulence factor delivery. Our results
      reveal that control of sugar uptake, managed by regulation of a host sugar
      transporter, is a defense strategy deployed against microbial infection.
      Competition for sugar thus shapes host-pathogen interactions.

PMID- 27884940
TI  - Ecological speciation of bacteriophage lambda in allopatry and sympatry.
AB  - Understanding the conditions that allow speciation to occur is difficult because
      most research has focused on either long-lived organisms or asexual
      microorganisms. We propagated bacteriophage lambda, a virus with rapid
      generations and frequent recombination, on two Escherichia coli host genotypes
      that expressed either the LamB or OmpF receptor. When supplied with either single
      host (allopatry), phage lambda improved its binding to the available receptor
      while losing its ability to use the alternative. When evolving on both hosts
      together (sympatry), the viruses split into two lineages with divergent receptor
      preferences. Although the level of divergence varied among replicates, some
      lineages evolved reproductive isolation via genetic incompatibilities. This
      outcome indicates that, under suitable conditions, allopatric and sympatric
      speciation can occur with similar ease.

PMID- 27884942
TI  - Severe Pancytopenia in a Premature Infant.

PMID- 27884941
TI  - Developing predictive models for return to work using the Military Power,
      Performance and Prevention (MP3) musculoskeletal injury risk algorithm: a study
      protocol for an injury risk assessment programme.
AB  - BACKGROUND: Musculoskeletal injuries are a primary source of disability in the US
      Military, and low back pain and lower extremity injuries account for over 44% of
      limited work days annually. History of prior musculoskeletal injury increases the
      risk for future injury. This study aims to determine the risk of injury after
      returning to work from a previous injury. The objective is to identify criteria
      that can help predict likelihood for future injury or re-injury. METHODS: There
      will be 480 active duty soldiers recruited from across four medical centres.
      These will be patients who have sustained a musculoskeletal injury in the lower
      extremity or lumbar/thoracic spine, and have now been cleared to return back to
      work without any limitations. Subjects will undergo a battery of physical
      performance tests and fill out sociodemographic surveys. They will be followed
      for a year to identify any musculoskeletal injuries that occur. Prediction
      algorithms will be derived using regression analysis from performance and
      sociodemographic variables found to be significantly different between injured
      and non-injured subjects. DISCUSSION: Due to the high rates of injuries, injury
      prevention and prediction initiatives are growing. This is the first study
      looking at predicting re-injury rates after an initial musculoskeletal injury. In
      addition, multivariate prediction models appear to have move value than models
      based on only one variable. This approach aims to validate a multivariate model
      used in healthy non-injured individuals to help improve variables that best
      predict the ability to return to work with lower risk of injury, after a recent
      musculoskeletal injury. TRIAL REGISTRATION NUMBER: NCT02776930.

PMID- 27884943
TI  - Recombinant Staphylococcal Enterotoxin Type A Stimulate Antitumoral Cytokines.
AB  - BACKGROUND: About 20 different types of staphylococcal enterotoxins are produced
      by Staphylococcus aureus, in which type A is more common in food poisoning
      syndrome. Also staphylococcal enterotoxin A superantigen is a potent inducer of
      cytotoxic T lymphocyte activity and cytokine production and could stimulate T
      cells containing T-cell receptor beta chain domains when binding to major
      histocompatibility complex class II molecules. Hence, it is an important reagent
      in cancer immunotherapy. METHODS: For the construction of pET-21a/ entA cassette,
      the staphylococcal enterotoxin type A gene was isolated from S aureus strain HN2,
      cloned into pET-21a, and introduced into Escherichia coli strain BL-21(DE3).
      Consequently, Western blot analysis showed pET-21a/ entA cassette expression
      inserted entA gene successfully. It is the first prompt using a pET-21a as a
      cloning vector for entA gene and expression of construct in BL-21(DE3). In
      addition, this study examined the ability of standard staphylococcal enterotoxin
      A and cloned staphylococcal enterotoxin A to activate T cells in vitro.
      Lymphocyte cells derived from lymph node BALB/c mice were exposed to standard
      staphylococcal enterotoxin A and cloned staphylococcal enterotoxin (1.10,
      102,103, and 104 ng/uL) in order to evaluate the magnitude of proliferation,
      activation, and apoptosis of lymphocyte cells based on MTT and apoptosis assays,
      respectively. RESULTS: Our investigation showed that the function of cloned
      staphylococcal enterotoxin A was same as standard staphylococcal enterotoxin A,
      and the optimal concentration for the activation of lymphocyte cells and
      induction of apoptosis was 100 ng/uL and 1000 ng/uL ( P < .05), respectively.
      Quantification of cytokines clearly showed that lymphocyte cells exposed to
      standard staphylococcal enterotoxin A and cloned staphylococcal enterotoxin A
      significantly secreted higher interferon gamma and tumor necrosis factor alpha
      compared to control. CONCLUSION: According to our results, the biological
      activity of standard staphylococcal enterotoxin A and cloned staphylococcal
      enterotoxin A is identical; therefore, these procedures may be approved as an
      efficient method to express and purify this protein in a large scale.

PMID- 27884944
TI  - Ruptured abdominal aortic aneurysm after endovascular aortic aneurysm repair
      thrombosis.
AB  - Background Complete thrombosis of an aortic endograft after an endovascular
      aortic aneurysm repair is a rare complication. The majority of thrombotic events
      occur in the iliac limbs. Case presentation We present the case of a patient who
      presented with acute limb ischemia as the result of a thrombosed infra-renal
      aortic endograft. After restoration of blood flow to the lower extremities with
      an axillary to bi-femoral artery bypass, the patient was lost to follow-up. The
      patient returned two years later with a ruptured abdominal aortic aneurysm due to
      a type 1A endoleak. Discussion We propose that all patients after endovascular
      aortic aneurysm repair, including those with a thrombosed aortic endograft,
      continue to undergo regular graft surveillance. This case report highlights the
      importance of continued surveillance of the aortic sac, even after total
      thrombosis of the endovascular aortic aneurysm repair.

PMID- 27884945
TI  - Evaluation of European Domestic Violence Perpetrator Programmes: Toward a Model
      for Designing and Reporting Evaluations Related to Perpetrator Treatment
      Interventions.
AB  - This article is based on a review of 60 evaluations (published and unpublished)
      relating to European domestic violence perpetrator programmes, involving 7,212
      programme participants across 12 countries. The purpose of the review, part of
      the "IMPACT: Evaluation of European Perpetrator Programmes" project funded by the
      European Commission (Daphne III Programme), was to provide detailed knowledge
      about the range of European evaluation studies with particular emphasis on the
      design, methods, input, output, and outcome measures used in order to identify
      the possibilities and challenges of a multicountry, Europe-wide evaluation
      methodology that could be used to assess perpetrator programmes in the future. We
      provide a model to standardise the reporting of evaluation studies and to ensure
      attention is paid to what information is being collected at different time points
      so as to understand what and how the behaviour and attitudes of perpetrators
      might change throughout the course of the programme.

PMID- 27884948
TI  - Enteral feeding in motor neurone disease: Patients' perspectives and impact on
      quality of life.

PMID- 27884947
TI  - The Effect of Smartphone-Delivered Emergency Preparedness Education on Coping
      Knowledge Among Fifth- and Sixth-Grade Elementary Schoolchildren in South Korea.
AB  - This study examined the effect of an intervention on coping knowledge among fifth
      and sixth-grade elementary schoolchildren who received smartphone-delivered
      emergency preparedness education. This was a quasi-experimental study using a pre
      /posttest design. Eighty-six children were recruited to participate. The children
      in the experimental group ( n = 44) received smartphone-delivered emergency
      preparedness education while those in the control group ( n = 42) received
      traditional lecture-centered education. Data were analyzed using a repeated
      measured analysis of variance. Subsequently, the experimental group scored
      significantly higher than the control group on coping knowledge ( F = 7.96, f =
      .31, p = .010). The use of technology such as smartphone-delivered emergency
      preparedness education may be effective to improve their coping knowledge of
      fifth- and sixth-grade elementary schoolchildren.

PMID- 27884949
TI  - Control of blood pressure and cardiovascular risk in Moroccan patients with newly
      diagnosed hypertension: a 3-month observational study in primary care.
AB  - BACKGROUND: Control of blood pressure and reduction of cardiovascular risk
      factors are mandatory in patients with hypertension. The aim of this study was to
      determine the proportion of patients with controlled hypertension and to describe
      the cardiovascular risk profile in hypertensive patients followed by general
      practitioners (GPs) in Morocco. METHODS: This national, observational,
      multicentre, prospective, longitudinal study of patients with newly diagnosed
      hypertension was carried out between September 2011 and December 2011. The use of
      antihypertensive drugs was evaluated at inclusion and after 3 months of follow
      up. Uncontrolled hypertension was defined as systolic blood pressure (SBP) ? 140
      mmHg or diastolic blood pressure (DBP) ? 90 mmHg at 3 months of follow up. The
      SCORE scale issued by the European Society of Cardiology (ESC) was used to assess
      overall cardiovascular risk and probability of experiencing a cardiovascular
      event within 10 years. RESULTS: A total of 909 hypertensive patients were
      recruited (62.4% female). Mean age was 56.8 +/- 10.6 years. More than half of the
      patients (53.0%) were between 40-60 years and more than one-third (34.1%) were
      obese [body mass index (BMI) ? 30 kg/m2]. There were significantly more obese
      females than males ( p < 0.001). Over half of the patients (52.5%) had a high or
      extremely high cardiovascular risk. Abdominal obesity (measured as waist
      circumference) was the most common cardiovascular risk factor (61.7%) followed by
      age (40.5%), dyslipidaemia (36.3%) and diabetes (34.3%). Mean SBP decreased from
      168.1 +/- 14.8 to 138.3 +/- 13.2 mmHg ( p < 0.001) and mean DBP decreased from
      93.0 +/- 10.5 to 81.0 +/- 8.6 mmHg ( p < 0.001) after 3 months of treatment.
      Control of blood pressure was achieved in only 46.8% of patients. Poor compliance
      (17.1%) and a lack of treatment efficacy (16.9%) were the two main reasons for
      not achieving the blood pressure target. CONCLUSIONS: More than half (53.2%) of
      the hypertensive patients in our study did not achieve adequate blood pressure
      control during the 3-month follow-up period and had a high cardiovascular risk.
      More effective management of hypertension is required in primary care.

PMID- 27884951
TI  - Glycaemic control by monoamine oxidase inhibition in a patient with type 1
      diabetes.
AB  - We present clinical, electroencephalographic and low-resolution electromagnetic
      tomography data that support combined treatment with insulin and a monoamine
      oxidase inhibitor in a patient with type 1 diabetes. We suggest that brain
      imaging data can identify a subgroup of patients who are likely to benefit from
      an insulin regimen and monoamine oxidase inhibition to improve glycaemic control,
      cardiovascular function, normalize the circadian rhythm and restore perception of
      glycaemic awareness.

PMID- 27884950
TI  - Neutrophil Extracellular Traps in the Amniotic Cavity of Women with Intra
      Amniotic Infection: A New Mechanism of Host Defense.
AB  - OBJECTIVE: Neutrophil extracellular traps (NETs) control microbial infections
      through their antimicrobial activities attributed to DNA, histones, granules, and
      cytoplasmic proteins (eg, elastase). Intra-amniotic infection is characterized by
      the influx of neutrophils into the amniotic cavity; therefore, the aim of this
      study was to determine whether amniotic fluid neutrophils form NETs in this
      inflammatory process. METHODS: Amniotic fluid samples from women with intra
      amniotic infection (n = 15) were stained for bacteria detection using fluorescent
      dyes. Amniotic fluid neutrophils were purified by filtration. As controls,
      neutrophils from maternal blood samples (n = 3) were isolated by density
      gradients. Isolated neutrophils were plated onto glass cover slips for culture
      with and without 100 nM of phorbol-12-myristate-13-acetate (PMA). NET formation
      was assessed by 4',6-diamidino-2-phenylindole (DAPI) staining and scanning
      electron microscopy. Different stages of NET formation were visualized using
      antibodies against elastase and histone H3, in combination with DAPI staining, by
      confocal microscopy. Finally, maternal or neonatal neutrophils were added to
      amniotic fluid samples from women without intra-amniotic infection (n = 4), and
      NET formation was evaluated by DAPI staining. RESULTS: (1) NETs were present in
      the amniotic fluid of women with intra-amniotic infection; (2) all of the
      amniotic fluid samples had detectable live and dead bacteria associated with the
      presence of NETs; (3) in contrast to neutrophils from the maternal circulation,
      amniotic fluid neutrophils did not require PMA stimulation to form NETs; (4)
      different stages of NET formation were observed by co-localizing elastase,
      histone H3, and DNA in amniotic fluid neutrophils; and (5) neither maternal nor
      neonatal neutrophils form NETs in the amniotic fluid of women without intra
      amniotic infection. CONCLUSION: NETs are detectable in the amniotic fluid of
      women with intra-amniotic infection.

PMID- 27884952
TI  - How Violence Constitutes Order: Consent, Coercion, and Censure in Tanzania.
AB  - Survey data show that most Tanzanian women find wife-beating justifiable. What is
      the meaning of the violence that enjoys such broad social approval? Does respect
      for women's agency invalidate feminist opposition to wife-beating? I explore
      these questions by analyzing data on hegemonic norms generated through 27 focus
      group discussions in Arumeru and Kigoma-Vijijini districts, and find that wife
      beating was supported for its role in constituting social order. This analysis of
      how exactly violence can constitute order yielded insights into the interplay
      between violence and consent that are theoretically relevant to violence against
      women in other forms and contexts, reminding researchers and practitioners of the
      role of power and coercion in supposedly agreed-upon community norms.

PMID- 27884946
TI  - Analysis of the Caenorhabditis elegans innate immune response to Coxiella
      burnetii.
AB  - The nematode Caenorhabditis elegans is well established as a system for
      characterization and discovery of molecular mechanisms mediating microbe-specific
      inducible innate immune responses to human pathogens. Coxiella burnetii is an
      obligate intracellular bacterium that causes a flu-like syndrome in humans (Q
      fever), as well as abortions in domesticated livestock, worldwide. Initially,
      when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C.
      burnetii (CCB) a number of overt pathological manifestations resulted, including
      intestinal distension, deformed anal region and a decreased lifespan. However,
      nematodes fed autoclave-killed CCB did not exhibit these symptoms. Although
      vertebrates detect C. burnetii via TLRs, pathologies in tol-1(-) mutant nematodes
      were indistinguishable from N2, and indicate nematodes do not employ this
      orthologue for detection of C. burnetii. sek-1(-) MAP kinase mutant nematodes
      succumbed to infection faster, suggesting that this signaling pathway plays a
      role in immune activation, as previously shown for orthologues in vertebrates
      during a C. burnetii infection. C. elegans daf-2(-) mutants are hyper-immune and
      exhibited significantly reduced pathological consequences during challenge.
      Collectively, these results demonstrate the utility of C. elegans for studying
      the innate immune response against C. burnetii and could lead to discovery of
      novel methods for prevention and treatment of disease in humans and livestock.

PMID- 27884953
TI  - Postpartum Domestic Violence in Homes With Young Children: The Role of Maternal
      and Paternal Drinking.
AB  - There has been limited investigation of mothers' drinking patterns and their
      experience of domestic abuse while parenting young children, especially in the
      context of co-resident fathers' drinking. Using data representative of the 2001
      U.S. birth cohort, the authors conducted longitudinal latent class analyses of
      maternal drinking over four perinatal time points as predictors of maternal
      victimization at 2 years postpartum due to intimate partner violence. Women
      classified as higher risk drinkers over the study period faced significantly
      increased risk of physical abuse while parenting a 2-year-old child. Among non
      drinking mothers, paternal binge drinking signaled additional risk, with clinical
      and programmatic implications.

PMID- 27884954
TI  - Impact of external pneumatic compression target inflation pressure on
      transcriptome-wide RNA expression in skeletal muscle.
AB  - Next-generation RNA sequencing was employed to determine the acute and subchronic
      impact of peristaltic pulse external pneumatic compression (PEPC) of different
      target inflation pressures on global gene expression in human vastus lateralis
      skeletal muscle biopsy samples. Eighteen (N = 18) male participants were randomly
      assigned to one of the three groups: (1) sham (n = 6), 2) EPC at 30-40 mmHg (LP
      EPC; n = 6), and 3) EPC at 70-80 mmHg (MP-EPC; n = 6). One hour treatment with
      sham/EPC occurred for seven consecutive days. Vastus lateralis skeletal muscle
      biopsies were performed at baseline (before first treatment; PRE), 1 h following
      the first treatment (POST1), and 24 h following the last (7th) treatment (POST2).
      Changes from PRE in gene expression were analyzed via paired comparisons within
      each group. Genes were filtered to include only those that had an RPKM >= 1.0, a
      fold-change of >=1.5 and a paired t-test value of <0.01. For the sham condition,
      two genes at POST1 and one gene at POST2 were significantly altered. For the LP
      EPC condition, nine genes were up-regulated and 0 genes were down-regulated at
      POST1 while 39 genes were up-regulated and one gene down-regulated at POST2. For
      the MP-EPC condition, two genes were significantly up-regulated and 21 genes were
      down-regulated at POST1 and 0 genes were altered at POST2. Both LP-EPC and MP-EPC
      acutely alter skeletal muscle gene expression, though only LP-EPC appeared to
      affect gene expression with subchronic application. Moreover, the transcriptome
      response to EPC demonstrated marked heterogeneity (i.e., genes and
      directionality) with different target inflation pressures.

PMID- 27884955
TI  - Effect of exercise-induced muscle damage on vascular function and skeletal muscle
      microvascular deoxygenation.
AB  - This paper investigated the effects of unaccustomed eccentric exercise-induced
      muscle damage (EIMD) on macro- and microvascular function. We tested the
      hypotheses that resting local and systemic endothelial-dependent flow-mediated
      dilation (FMD) and microvascular reactivity would decrease, VO2max would be
      altered, and that during ramp exercise, peripheral O2 extraction, evaluated via
      near-infrared-derived spectroscopy (NIRS) derived deoxygenated hemoglobin +
      myoglobin ([HHb]), would be distorted following EIMD In 13 participants,
      measurements were performed prior to (Pre) and 48 h after a bout of knee extensor
      eccentric exercise designed to elicit localized muscle damage (Post). Flow
      mediated dilation and postocclusive reactive hyperemic responses measured in the
      superficial femoral artery served as a measurement of local vascular function
      relative to the damaged tissue, while the brachial artery served as an index of
      nonlocal, systemic, vascular function. During ramp-incremental exercise on a
      cycle ergometer, [HHb] and tissue saturation (TSI%) in the m. vastus lateralis
      were measured. Superficial femoral artery FMD significantly decreased following
      EIMD (pre 6.75 +/- 3.89%; post 4.01 +/- 2.90%; P < 0.05), while brachial artery
      FMD showed no change. The [HHb] and TSI% amplitudes were not different following
      EIMD ([HHb]: pre, 16.9 +/- 4.7; post 17.7 +/- 4.9; TSI%: pre, 71.0 +/- 19.7; post
      71.0 +/- 19.7; all P > 0.05). At each progressive increase in workload (i.e., 0
      100% peak), the [HHb] and TOI% responses were similar pre- and 48 h post-EIMD (P
      > 0.05). Additionally, VO2max was similar at pre- (3.0 +/- 0.67 L min-1) to 48 h
      post (2.96 +/- 0.60 L min-1)-EIMD (P > 0.05). Results suggest that moderate
      eccentric muscle damage leads to impaired local, but not systemic, macrovascular
      dysfunction.

PMID- 27884956
TI  - Regional effects of streptozotocin-induced diabetes on shortening and calcium
      transport in epicardial and endocardial myocytes from rat left ventricle.
AB  - In the heart, the left ventricle pumps blood at higher pressure than the right
      ventricle. Within the left ventricle, the electromechanical properties of
      ventricular cardiac myocytes vary transmurally and this may be related to the
      gradients of stress and strain experienced in vivo across the ventricular wall.
      Diabetes is also associated with alterations in hemodynamic function. The aim of
      this study was to investigate shortening and Ca2+ transport in epicardial (EPI)
      and endocardial (ENDO) left ventricular myocytes in the streptozotocin (STZ)
      induced diabetic rat. Shortening, intracellular Ca2+ and L-type Ca2+ current
      (ICa,L) were measured by video detection, fura-2 microfluorimetry, and whole-cell
      patch clamp techniques, respectively. Time to peak (TPK) shortening was prolonged
      to similar extents in ENDO and EPI myocytes from STZ-treated rats compared to
      ENDO and EPI myocytes from controls. Time to half (THALF) relaxation of
      shortening was prolonged in ENDO myocytes from STZ-treated rats compared to ENDO
      controls. TPK Ca2+ transient was prolonged in ENDO myocytes from STZ-treated rats
      compared to ENDO controls. THALF decay of the Ca2+ transient was prolonged in
      ENDO myocytes from STZ-treated rats compared to ENDO controls. Sarcoplasmic
      reticulum (SR) fractional release of Ca2+ was reduced in EPI myocytes from STZ
      treated rats compared to EPI controls. ICa,L activation, inactivation, and
      recovery from inactivation were not significantly altered in EPI and ENDO
      myocytes from STZ-treated rats or controls. Regional differences in Ca2+
      transport may partly underlie differences in ventricular myocyte shortening
      across the wall of the healthy and the STZ-treated rat left ventricle.

PMID- 27884957
TI  - Altered CO2 sensitivity of connexin26 mutant hemichannels in vitro.
AB  - Connexin26 (Cx26) mutations underlie human pathologies ranging from hearing loss
      to keratitis ichthyosis deafness (KID) syndrome. Cx26 hemichannels are directly
      gated by CO2 and contribute to the chemosensory regulation of breathing. The KID
      syndrome mutation A88V is insensitive to CO2, and has a dominant negative action
      on the CO2 sensitivity of Cx26WT hemichannels, and reduces respiratory drive in
      humans. We have now examined the effect of further human mutations of Cx26 on its
      sensitivity to CO2 : Mutated Cx26 subunits, carrying one of A88S, N14K, N14Y,
      M34T, or V84L, were transiently expressed in HeLa cells. The CO2-dependence of
      hemichannel activity, and their ability to exert dominant negative actions on
      cells stably expressing Cx26WT, was quantified by a dye-loading assay. The KID
      syndrome mutation, N14K, abolished the sensitivity of Cx26 to CO2 Both N14Y and
      N14K exerted a powerful dominant negative action on the CO2 sensitivity of Cx26WT
      None of the other mutations (all recessive) had a dominant negative action. A88S
      shifted the affinity of Cx26 to slightly higher levels without reducing its
      ability to fully open to CO2 M34T did not change the affinity of Cx26 for CO2 but
      reduced its ability to open in response to CO2 V84L had no effect on the CO2
      sensitivity of Cx26. Some pathological mutations of Cx26 can therefore alter the
      CO2 sensitivity of Cx26 hemichannels. The loss of CO2 sensitivity could
      contribute to pathology and consequent reduced respiratory drive could be an
      unrecognized comorbidity of these pathologies.

PMID- 27884958
TI  - Activity-dependent redistribution of Kv2.1 ion channels on rat spinal
      motoneurons.
AB  - Homeostatic plasticity occurs through diverse cellular and synaptic mechanisms,
      and extensive investigations over the preceding decade have established Kv2.1 ion
      channels as key homeostatic regulatory elements in several central neuronal
      systems. As in these cellular systems, Kv2.1 channels in spinal motoneurons (MNs)
      localize within large somatic membrane clusters. However, their role in
      regulating motoneuron activity is not fully established in vivo. We have
      previously demonstrated marked Kv2.1 channel redistribution in MNs following in
      vitro glutamate application and in vivo peripheral nerve injury (Romer et al.,
      2014, Brain Research, 1547:1-15). Here, we extend these findings through the
      novel use of a fully intact, in vivo rat preparation to show that Kv2.1 ion
      channels in lumbar MNs rapidly and reversibly redistribute throughout the somatic
      membrane following 10 min of electrophysiological sensory and/or motor nerve
      stimulation. These data establish that Kv2.1 channels are remarkably responsive
      in vivo to electrically evoked and synaptically driven action potentials in MNs,
      and strongly implicate motoneuron Kv2.1 channels in the rapid homeostatic
      response to altered neuronal activity.

PMID- 27884959
TI  - Cardiac responses to exercise distinguish postural orthostatic tachycardia
      syndrome variants.
AB  - We previously showed that one-third of adolescents with postural orthostatic
      tachycardia syndrome (POTS) have hyperkinetic circulation. In a subsequent
      cohort, we compare participants with POTS grouped according to cardiac output (Q)
      versus oxygen uptake (VO2) function, whose circulatory response to exercise lay
      at the lower end of this distribution. We hypothesized that such grouping
      determines the circulatory response to incremental-protocol, upright, cycle
      ergometry by whatever blend of flow and resistance adjustments best maintains
      normal blood pressure. We reviewed data on 209 POTS participants aged 10-19 years
      (73% female) grouped as follows: Q-VO2 < 3.20 L.min-1 per L.min-1 were designated
      low Q or hypokinetic variant (N = 31); normal-Q had slopes between 3.21 and 7.97;
      hyperkinetic participants had Q-VO2 slope >8 L.min-1 per L.min-1 (N = 32). Heart
      rate response to exercise was virtually identical in each group. Mean stroke
      volume (SV) rose normally in the hyperkinetic group (51 +/- 38%); less in the
      normal Q group (22 +/- 27%); but was flat in the low Q group (-7 +/- 16%). Mean
      arterial pressure was similar at rest while systemic vascular conductance was
      flat from rest to exercise in the hypokinetic group, and by comparison rose more
      steeply in the normal Q (P < 0.001) and in the hyperkinetic (P = 0.02) groups. In
      conclusion, we identified a variant of POTS with a hypokinetic circulation
      maintained by a vasoconstricted state. We speculate that they cannot muster
      preload to augment exercise SV due to profound thoracic hypovolemia, and must
      resort to vasoconstriction in order to maintain perfusion pressure within working
      muscle.

PMID- 27884960
TI  - Can inorganic phosphate explain sag during unfused tetanic contractions of
      skeletal muscle?
AB  - We test the hypothesis that cytosolic inorganic phosphate (Pi) can account for
      the contraction-induced reductions in twitch duration which impair summation and
      cause force to decline (sag) during unfused tetanic contractions of fast-twitch
      muscle. A five-state model of crossbridge cycling was used to simulate twitch and
      unfused tetanic contractions. As Pi concentration ([Pi]) was increased from 0 to
      30 mmol.L-1, twitch duration decreased, with progressive reductions in
      sensitivity to Pi as [Pi] was increased. When unfused tetani were simulated with
      rising [Pi], sag was most pronounced when initial [Pi] was low, and when the
      magnitude of [Pi] increase was large. Fast-twitch extensor digitorum longus (EDL)
      muscles (sag-prone, typically low basal [Pi]) and slow-twitch soleus muscles (sag
      resistant, typically high basal [Pi]) were isolated from 14 female C57BL/6 mice.
      Muscles were sequentially incubated in solutions containing either glucose or
      pyruvate to create typical and low Pi environments, respectively. Twitch duration
      was greater (P < 0.05) in pyruvate than glucose in both muscles. Stimuli applied
      at intervals approximately three times the time to peak twitch tension resulted
      in sag of 35.0 +/- 3.7% in glucose and 50.5 +/- 1.4% in pyruvate in the EDL
      (pyruvate > glucose; P < 0.05), and 3.9 +/- 0.3% in glucose and 37.8 +/- 2.7% in
      pyruvate in the soleus (pyruvate > glucose; P < 0.05). The influence of Pi on
      crossbridge cycling provides a tenable mechanism for sag. Moreover, the low basal
      [Pi] in fast-twitch relative to slow-twitch muscle has promise as an explanation
      for the fiber-type dependency of sag.

PMID- 27884961
TI  - Therapeutic silencing of fat-specific protein 27 improves glycemic control in
      mouse models of obesity and insulin resistance.
AB  - Obesity is a component of the metabolic syndrome, mechanistically linked to
      diabetes, fatty liver disease, and cardiovascular disease. Proteins that regulate
      the metabolic fate of intracellular lipid droplets are potential therapeutic
      candidates to treat obesity and its related consequences. CIDEC (cell death
      inducing DFFA-like effector C), also known in mice as Fsp27 (fat-specific protein
      27), is a lipid droplet-associated protein that prevents lipid mobilization and
      promotes intracellular lipid storage. The consequences of complete loss of FSP27
      on hepatic metabolism and on insulin resistance are controversial, as both
      healthy and deleterious lipodystrophic phenotypes have been reported in Fsp27-/-
      mice. To test whether therapeutic silencing of Fsp27 might be useful to improve
      obesity, fatty liver, and glycemic control, we used antisense oligonucleotides
      (ASOs) in both nutritional (high-fat diet) and genetic (leptin-deficient ob/ob)
      mouse models of obesity, hyperglycemia, and hepatosteatosis. We show that partial
      silencing Fsp27 in either model results in the robust decrease in visceral fat,
      improved insulin sensitivity and whole-body glycemic control, and tissue-specific
      changes in transcripts controlling lipid oxidation and synthesis. These data
      suggest that partial reduction of FSP27 activity (e.g., using ASOs) might be
      exploited therapeutically in insulin-resistant obese or overweight patients.

PMID- 27884962
TI  - Triheptanoin: long-term effects in the very long-chain acyl-CoA dehydrogenase
      deficient mouse.
AB  - A rather new approach in the treatment of long-chain fatty acid oxidation
      disorders is represented by triheptanoin, a triglyceride with three medium-odd
      chain heptanoic acids (C7), due to its anaplerotic potential. We here investigate
      the effects of a 1-year triheptanoin-based diet on the clinical phenotype of very
      long-chain-acyl-CoA-dehydrogenase-deficient (VLCAD-/-) mice. The cardiac function
      was assessed in VLCAD-/- mice by in vivo MRI. Metabolic adaptations were
      identified by the expression of genes regulating energy metabolism and
      anaplerotic processes using real-time PCR, and the results were correlated with
      the measurement of the glycolytic enzymes pyruvate dehydrogenase and pyruvate
      kinase. Finally, the intrahepatic lipid accumulation and oxidative stress in
      response to the long-term triheptanoin diet were assessed. Triheptanoin was not
      able to prevent the development of systolic dysfunction in VLCAD-/- mice despite
      an upregulation of cardiac glucose oxidation. Strikingly, the anaplerotic effects
      of triheptanoin were restricted to the liver. Despite this, the hepatic lipic
      content was increased upon triheptanoin supplementation. Our data demonstrate
      that the concept of anaplerosis does not apply to all tissues equally.

PMID- 27884964
TI  - What are the characteristics of, and clinical outcomes in men who have sex with
      men prescribed HIV postexposure prophylaxis following sexual exposure (PEPSE) at
      sexual health clinics in England?
AB  - OBJECTIVES: To explore the risk factors for, and clinical outcomes in men who
      have sex with men (MSM) prescribed HIV postexposure prophylaxis following sexual
      exposure (PEPSE) at sexual health clinics (SHCs) in England. METHODS: National
      STI surveillance data were extracted from the genitourinary medicine clinic
      activity dataset (GUMCADv2) for 2011-2014. Quarterly and annual trends in the
      number of episodes where PEPSE was prescribed were analysed by gender and sexual
      risk. Risk factors associated with being prescribed PEPSE among MSM attendees
      were explored using univariable and multivariable logistic regression. Subsequent
      HIV acquisition from 4 months after initiating PEPSE was assessed using
      multivariable Cox proportional hazards models, stratified by clinical risk
      profiles. RESULTS: During 2011-2014, there were 24 004 episodes where PEPSE was
      prescribed at SHCs, of which 69% were to MSM. The number of episodes where PEPSE
      was prescribed to MSM increased from 2383 in 2011 to 5944 in 2014, and from 1384
      to 2226 for heterosexual men and women. 15% of MSM attendees received two or more
      courses of PEPSE. Compared with MSM attendees not prescribed PEPSE, MSM
      prescribed PEPSE were significantly more likely to have been diagnosed with a
      bacterial STI in the previous 12 months (adjusted OR (95% CI)-gonorrhoea: 11.6
      (10.5 to 12.8); chlamydia: 5.02 (4.46 to 5.67); syphilis: 2.25 (1.73 to 2.93)),
      and were more likely to subsequently acquire HIV (adjusted HR (aHR) (95% CI)
      single PEPSE course: 2.54 (2.19 to 2.96); two or more PEPSE courses: aHR (95% CI)
      4.80 (3.69 to 6.25)). The probability of HIV diagnosis was highest in MSM
      prescribed PEPSE who had also been diagnosed with a bacterial STI in the previous
      12 months (aHR (95% CI): 6.61 (5.19 to 8.42)). CONCLUSIONS: MSM prescribed PEPSE
      are at high risk of subsequent HIV acquisition and our data show further risk
      stratification by clinical and PEPSE prescribing history is possible, which might
      inform clinical practice and HIV prevention initiatives in MSM.

PMID- 27884963
TI  - Ectopic fat deposition contributes to age-associated pathology in Caenorhabditis
      elegans.
AB  - Age-dependent collapse of lipid homeostasis results in spillover of lipids and
      excessive fat deposition in nonadipose tissues. Ectopic fat contributes to
      lipotoxicity and has been implicated in the development of a metabolic syndrome
      that increases risk of age-associated diseases. However, the molecular mechanisms
      coupling ectopic fat accumulation with aging remain obscure. Here, we use
      nonlinear imaging modalities to visualize and quantify age-dependent ectopic
      lipid accumulation in Caenorhabditis elegans We find that aging is accompanied by
      pronounced deposition of lipids in nonadipose tissues, including the nervous
      system. Importantly, interventions that promote longevity such as low insulin
      signaling, germ-line loss, and dietary restriction, which effectively delay aging
      in evolutionary divergent organisms, diminish the rate of ectopic fat
      accumulation and the size of lipid droplets. Suppression of lipotoxic
      accumulation of fat in heterologous tissues is dependent on helix-loop-helix
      (HLH)-30/transcription factor EB (TFEB) and autophagy. Our findings in their
      totality highlight the pivotal role of HLH-30/TFEB and autophagic processes in
      the maintenance of lipid homeostasis during aging, in addition to establishing
      nonlinear imaging as a powerful tool for monitoring ectopic lipid droplet
      deposition in vivo.

PMID- 27884965
TI  - 'Can you recommend any good STI apps?' A review of content, accuracy and
      comprehensiveness of current mobile medical applications for STIs and related
      genital infections.
AB  - OBJECTIVE: Seeking sexual health information online is common, and provision of
      mobile medical applications (apps) for STIs is increasing. Young people,
      inherently at higher risk of STIs, are avid users of technology, and apps could
      be appealing sources of information. We undertook a comprehensive review of
      content and accuracy of apps for people seeking information about STIs. METHODS:
      Search of Google Play and iTunes stores using general and specific search terms
      for apps regarding STIs and genital infections (except HIV), testing, diagnosis
      and management, 10 September 2014 to 16 September 2014. We assessed eligible apps
      against (1) 19 modified Health on The Net (HON) Foundation principles; and (2)
      comprehensiveness and accuracy of information on STIs/genital infections, and
      their diagnosis and management, compared with corresponding National Health
      Service STI information webpage content. RESULTS: 144/6642 apps were eligible. 57
      were excluded after downloading. 87 were analysed. Only 29% of apps met >=6 HON
      criteria. Content was highly variable: 34/87 (39%) covered one or two infections;
      40 (46%) covered multiple STIs; 5 (6%) focused on accessing STI testing. 13 (15%)
      were fully, 46 (53%) mostly and 28 (32%) partially accurate. 25 (29%) contained
      >=1 piece of potentially harmful information. Apps available on both iOS and
      Android were more accurate than single-platform apps. Only one app provided fully
      accurate and comprehensive information on chlamydia. CONCLUSIONS: Marked
      variation in content, quality and accuracy of available apps combined with the
      nearly one-third containing potentially harmful information risks undermining
      potential benefits of an e-Health approach to sexual health and well-being.

PMID- 27884966
TI  - Setting up a Neuroscience Stroke and Rehabilitation Centre in Brunei Darussalam
      by a transcontinental on-site and telemedical cooperation.
AB  - Due to the world-wide aging population, there is a need for specialist
      neurological knowledge, treatment and care. Stroke treatment is effective in
      reducing mortality and disability, but it is still not available in many areas of
      the world. We describe the set-up process of a specialized Neuroscience, Stroke
      and Rehabilitation Centre in Brunei Darussalam (BNSRC) in cooperation with a
      German hospital. This study details the setup of a stroke-, neurological
      intensive care- and neurorehabilitation unit, laboratories and a telemedical
      network to perform all evidence-based stroke treatments. All neurological on-site
      services and the telemedical network were successfully established within a short
      time. After setup, 1386 inpatients and 1803 outpatients with stroke and stroke
      mimics were treated. All evidence-based stroke treatments including thrombolysis
      and hemicraniectomy could be performed. It is possible to establish evidence
      based modern stroke treatment within a short time period by a transcontinental on
      site and telemedical cooperation.

PMID- 27884967
TI  - The value of being biologically related to one's family.

PMID- 27884968
TI  - Dissenting from care.data: an analysis of opt-out forms.
AB  - BACKGROUND: Care.data was a programme of work led by NHS England for the
      extraction of patient-identifiable and coded information from general
      practitioner (GP) records for secondary uses. This study analyses the forms (on
      the websites of GP practices) which enabled patients to opt out. METHODS:
      Theoretical sampling and summative content analysis were used to collect and
      analyse dissent forms used by patients to opt out from care. DATA: Domains
      included basic information about the programme, types of objections and personal
      details required for identification purposes. RESULTS: One hundred opt-out forms
      were analysed. Fifty-four forms mentioned that this programme was run by NHS
      England. 81 forms provided two types of objections to data-sharing, and 15
      provided only one objection. Only 26 forms mentioned that direct care would not
      be affected and 32 that patients maintain their right to opt back anytime. All
      but one of the opt-out forms we reviewed requested the name of the person wishing
      to opt out. 94 required a date of birth and 33 an NHS number. 82 required an
      address, 42 a telephone number and 7 an email address. CONCLUSIONS: Numbers of
      patients (not) opting out should be treated with caution, because the variability
      of information provided and the varied options for dissent may have caused
      confusion among patients. To ensure that dissent is in accordance with individual
      preferences and moral values, we recommend that well-designed information
      material and standardised opt-out forms be developed for such data-sharing
      initiatives.

PMID- 27884969
TI  - Ethics knowledge of recent paediatric residency graduates: the role of residency
      ethics curricula.
AB  - OBJECTIVE: To evaluate the relationship between recently trained paediatricians'
      ethics knowledge and exposure to a formal ethics or professionalism curriculum
      during residency. METHODS: We conducted a cross-sectional survey of recently
      trained paediatricians which included a validated 23-item instrument called the
      Test of Residents' Ethics Knowledge for Pediatrics. The sample included
      paediatricians who completed medical school in 2006-2008, whose primary specialty
      was paediatrics or a paediatric subspecialty, and who completed paediatric
      residency training in 2010-2011. This sample was stratified based on residency
      programme variables: presence of a formal curriculum in ethics or
      professionalism, programme size and American Board of Pediatrics certifying exam
      passage rate. Paediatricians were randomly selected from each stratum for survey
      participation. RESULTS: Among the 370 responding paediatricians (55%), the mean
      knowledge score was 17.3 (SD 2.2) out of a possible 23. Presence of a formal
      curriculum in ethics and/or professionalism was not significantly associated with
      knowledge. Knowledge was lowest on items about parental requests for a child to
      undergo genetic testing (2 items, 44% and 85% incorrect), preserving patient
      confidentiality over email (55% incorrect), decision-making regarding life
      sustaining technologies (61% incorrect), and decision-making principles such as
      assent and parental permission (2 items, 47% and 49% incorrect). CONCLUSIONS:
      This study highlights several areas in which paediatricians' knowledge may be low
      and that are amenable to targeted educational interventions. These findings
      should prompt discussion and research among ethicists and educators about how
      ethics and professionalism curricula can more consistently influence
      paediatricians' knowledge.

PMID- 27884970
TI  - Ethics briefing.

PMID- 27884972
TI  - Increased serum hepcidin contributes to the anemia of chronic kidney disease in a
      murine model.

PMID- 27884971
TI  - Progression in patients with low- and intermediate-1-risk del(5q) myelodysplastic
      syndromes is predicted by a limited subset of mutations.
AB  - A high proportion of patients with lower-risk del(5q) myelodysplastic syndromes
      will respond to treatment with lenalidomide. The median duration of transfusion
      independence is 2 years with some long-lasting responses, but almost 40% of
      patients progress to acute leukemia by 5 years after starting treatment. The
      mechanisms underlying disease progression other than the well-established finding
      of small TP53-mutated subclones at diagnosis remain unclear. We studied a
      longitudinal cohort of 35 low- and intermediate-1-risk del(5q) patients treated
      with lenalidomide (n=22) or not (n=13) by flow cytometric surveillance of
      hematopoietic stem and progenitor cell subsets, targeted sequencing of mutational
      patterns, and changes in the bone marrow microenvironment. All 13 patients with
      disease progression were identified by a limited number of mutations in TP53,
      RUNX1, and TET2, respectively, with PTPN11 and SF3B1 occurring in one patient
      each. TP53 mutations were found in seven of nine patients who developed acute
      leukemia, and were documented to be present in the earliest sample (n=1) and
      acquired during lenalidomide treatment (n=6). By contrast, analysis of the
      microenvironment, and of hematopoietic stem and progenitor cells by flow
      cytometry was of limited prognostic value. Based on our data, we advocate
      conducting a prospective study aimed at investigating, in a larger number of
      cases of del(5q) myelodysplastic syndromes, whether the detection of such
      mutations before and after lenalidomide treatment can guide clinical decision
      making.

PMID- 27884973
TI  - The emerging role of immune checkpoint inhibition in malignant lymphoma.
AB  - To evade elimination by the host immune system, tumor cells commonly exploit
      physiological immune checkpoint pathways, restraining efficient anti-tumor immune
      cell function. Growing understanding of the complex dialog between tumor cells
      and their microenvironment contributed to the development of immune checkpoint
      inhibitors. This innovative strategy has demonstrated paradigm-shifting clinical
      activity in various malignancies. Antibodies targeting programmed death 1 and
      cytotoxic T-lymphocyte-associated protein-4 are also being investigated in
      lymphoid malignancies with varying levels of activity and a favorable toxicity
      profile. To date, evaluated only in the setting of relapsed or refractory
      disease, anti-programmed death 1 antibodies such as nivolumab and pembrolizumab
      show encouraging response rates particularly in classical Hodgkin lymphoma but
      also in follicular lymphoma and diffuse-large B-cell lymphoma. As the first
      immune checkpoint inhibitor in lymphoma, nivolumab was approved for the treatment
      of relapsed or refractory classical Hodgkin lymphoma by the Food and Drug
      Administration in May 2016. In this review, we assess the role of the pathways
      involved and potential rationale of checkpoint inhibition in various lymphoid
      malignancies. In addition to data from current clinical trials, immune-related
      side effects, potential limitations and future perspectives including promising
      combinatory approaches with immune checkpoint inhibition are discussed.

PMID- 27884976
TI  - The career of William Osler.

PMID- 27884974
TI  - From leeches to personalized medicine: evolving concepts in the management of
      polycythemia vera.
AB  - Polycythemia vera is a clonal disorder of hematopoietic stem/progenitor cells. It
      manifests as an expansion of red cell mass. It is the most common chronic
      myeloproliferative neoplasm. In virtually all cases, it is characterized by a
      V617F point mutation in JAK2 exon 14 or less common mutations in exon 12. The
      landmark discovery of the autonomously activated JAK/STAT signaling pathway paved
      the way for the clinical development of the first target drug, the JAK1 and JAK2
      inhibitor ruxolitinib. This is now approved for patients with resistance or
      intolerance to hydroxyurea. Phlebotomies and hydroxyurea are still the
      cornerstone of treatment, and aim to prevent the first appearance or recurrence
      of cardiovascular events that, together with progression to post-polycythemia
      vera myelofibrosis and leukemia, represent the main causes of death. Interferon
      alpha is an alternative drug and has been shown to induce molecular remissions.
      It is currently undergoing phase III trials that might eventually lead to its
      approval for clinical use. The last few years have witnessed important advances
      towards an accurate early diagnosis of polycythemia vera, greater understanding
      of its pathogenesis, and improved patient management. This review will focus on
      the most recent achievements and will aim to unify the different concepts
      involved in a personalized approach to the patient with polycythemia vera. In
      spite of many recent advances in the understanding of its pathogenesis and
      improved disease management, polycythemia vera remains a life-threatening
      myeloproliferative neoplasm for which there is no cure. This review will present
      a critical overview of evolving concepts in diagnosis and treatment of this
      disease.

PMID- 27884975
TI  - Different clinical characteristics of paroxysmal nocturnal hemoglobinuria in
      pediatric and adult patients.

PMID- 27884977
TI  - NANOG regulates epithelial-mesenchymal transition and chemoresistance in ovarian
      cancer.
AB  - A key transcription factor associated with poor prognosis and resistance to
      chemotherapy in ovarian cancer is NANOG. However, the mechanism by which NANOG
      functions remains undefined. It has been suggested that epithelial-to-mesenchymal
      transition (EMT) also contributes to development of drug resistance in different
      cancers. We thus determined whether NANOG expression was associated with EMT and
      chemoresistance in epithelial ovarian cancer cells. NANOG expression was
      increased in epithelial ovarian cancer cell lines compared with its expression in
      normal epithelial ovarian cell lines. NANOG expression in SKOV-3 or OV2008 cells
      directly correlated with high expression of mesenchymal cell markers and
      inversely with low expression of epithelial cell marker. RNAi-mediated silencing
      of NANOG in SKOV-3 reversed the expression of mesenchymal cell markers and
      restored expression of E-cadherin. Reversibly, stable overexpression of NANOG in
      Moody cells increased expression of N-cadherin whereas down-regulating expression
      of E-cadherin, cumulatively indicating that NANOG plays an important role in
      maintaining the mesenchymal cell markers. Modulating NANOG expression did not
      have any effect on proliferation or colony formation. Susceptibility to cisplatin
      increased in SKOV-3 cells on down-regulating NANOG and reversible results were
      obtained in Moody cells post-overexpression of NANOG. NANOG silencing in SKOV-3
      and OV2008 robustly attenuated in vitro migration and invasion. NANOG expression
      exhibited a biphasic pattern in patients with ovarian cancer and expression was
      directly correlated to chemoresistance retrospectively. Cumulatively, our data
      demonstrate that NANOG expression modulates chemosensitivity and EMT resistance
      in ovarian cancer.

PMID- 27884979
TI  - Cost-Effectiveness of Behavior Activation Versus Supportive Therapy on Adherence
      to Eye Exams in Older African Americans With Diabetes.
AB  - Although the importance of ophthalmologic screening in diabetic patients is
      widely recognized by clinicians, the cost-effectiveness of strategies aimed at
      improving eye care utilization in this population is not well established. A cost
      effectiveness analysis was performed comparing behavior activation (BA) to
      supportive therapy (ST) in activating patients to receive a dilated fundus exam
      (DFE) and promoting healthy management of diabetes. Two hundred six subjects were
      randomized to receive either BA or ST between 2009 and 2013. Cost-effectiveness
      was calculated as incremental cost-effectiveness ratio (ICER) of BA versus ST.
      Total costs for BA and ST per participant were $259.02 and $216.12, respectively.
      At the 6-month follow-up, 87.91% of BA subjects received a DFE compared to 34.48%
      of ST subjects. The ICER for BA versus ST was $80.29/percent increase in DFE
      rate. In terms of improving DFE rates, BA was found to be more cost-effective
      than ST.

PMID- 27884980
TI  - An interactive three-dimensional digital atlas and quantitative database of human
      development.
AB  - Current knowledge about human development is based on the description of a
      limited number of embryonic specimens published in original articles and
      textbooks, often more than 100 years ago. It is exceedingly difficult to verify
      this knowledge, given the restricted availability of human embryos. We created a
      three-dimensional digital atlas and database spanning the first 2 months of human
      development, based on analysis of nearly 15,000 histological sections of the
      renowned Carnegie Collection of human embryonic specimens. We identified and
      labeled up to 150 organs and structures per specimen and made three-dimensional
      models to quantify growth, establish changes in the position of organs, and
      clarify current ambiguities. The atlas provides an educational and reference
      resource for studies on early human development, growth, and congenital
      malformations.

PMID- 27884982
TI  - News at a glance.

PMID- 27884983
TI  - Republicans ready a regulatory rollback.

PMID- 27884984
TI  - Gas changes signal eruptions.

PMID- 27884985
TI  - Catching ancient maize domestication in the act.

PMID- 27884981
TI  - Tissue damage and senescence provide critical signals for cellular reprogramming
      in vivo.
AB  - Reprogramming of differentiated cells into pluripotent cells can occur in vivo,
      but the mechanisms involved remain to be elucidated. Senescence is a cellular
      response to damage, characterized by abundant production of cytokines and other
      secreted factors that, together with the recruitment of inflammatory cells,
      result in tissue remodeling. Here, we show that in vivo expression of the
      reprogramming factors OCT4, SOX2, KLF4, and cMYC (OSKM) in mice leads to
      senescence and reprogramming, both coexisting in close proximity. Genetic and
      pharmacological analyses indicate that OSKM-induced senescence requires the
      Ink4a/Arf locus and, through the production of the cytokine interleukin-6,
      creates a permissive tissue environment for in vivo reprogramming. Biological
      conditions linked to senescence, such as tissue injury or aging, favor in vivo
      reprogramming by OSKM. These observations may be relevant for tissue repair.

PMID- 27884978
TI  - Oestrogen receptor negativity in breast cancer: a cause or consequence?
AB  - Endocrine resistance, which occurs either by de novo or acquired route, is posing
      a major challenge in treating hormone-dependent breast cancers by endocrine
      therapies. The loss of oestrogen receptor alpha (ERalpha) expression is the vital
      cause of establishing endocrine resistance in this subtype. Understanding the
      mechanisms that determine the causes of this phenomenon are therefore essential
      to reduce the disease efficacy. But how we negate oestrogen receptor (ER)
      negativity and endocrine resistance in breast cancer is questionable. To answer
      that, two important approaches are considered: (1) understanding the cellular
      origin of heterogeneity and ER negativity in breast cancers and (2)
      characterization of molecular regulators of endocrine resistance. Breast tumours
      are heterogeneous in nature, having distinct molecular, cellular, histological
      and clinical behaviour. Recent advancements in perception of the heterogeneity of
      breast cancer revealed that the origin of a particular mammary tumour phenotype
      depends on the interactions between the cell of origin and driver genetic hits.
      On the other hand, histone deacetylases (HDACs), DNA methyltransferases (DNMTs),
      miRNAs and ubiquitin ligases emerged as vital molecular regulators of ER
      negativity in breast cancers. Restoring response to endocrine therapy through re
      expression of ERalpha by modulating the expression of these molecular regulators
      is therefore considered as a relevant concept that can be implemented in treating
      ER-negative breast cancers. In this review, we will thoroughly discuss the
      underlying mechanisms for the loss of ERalpha expression and provide the future
      prospects for implementing the strategies to negate ER negativity in breast
      cancers.

PMID- 27884986
TI  - Graveyard of cold slabs mapped in Earth's mantle.

PMID- 27884987
TI  - Rogue protein's partners offer hope in Parkinson's disease.

PMID- 27884988
TI  - The wanderers.

PMID- 27884989
TI  - Research night owls.

PMID- 27884990
TI  - Proinflammatory primates.

PMID- 27884991
TI  - Closing the loop.

PMID- 27884992
TI  - Teaching nature the unnatural.

PMID- 27884994
TI  - Bringing order to neutral atom arrays.

PMID- 27884993
TI  - Mosquitoes on the move.

PMID- 27884995
TI  - Susan Lindquist (1949-2016).

PMID- 27884997
TI  - Toxic textiles.

PMID- 27884996
TI  - Ten policies for pollinators.

PMID- 27884999
TI  - Northeast Asia trip bolsters ongoing scientific cooperation.

PMID- 27884998
TI  - Embodied inequality.

PMID- 27885000
TI  - 2016 AAAS Fellows approved by the AAAS Council.

PMID- 27885001
TI  - On the clock.

PMID- 27885002
TI  - The scientific night shift.

PMID- 27885003
TI  - Circadian clocks: Not your grandfather's clock.
AB  - The last 20 years have seen the rapid evolution of our understanding of the
      molecular genes and networks that enable almost all forms of life to generate 24
      hour-or circadian-rhythms. One finding has been particularly exciting: that the
      molecular circadian clock resides in almost all of the cells of the body and that
      the clock regulates the timing of many cellular and signaling pathways associated
      with multiple disease states. Such advances represent a new frontier for
      medicine: circadian medicine.

PMID- 27885004
TI  - Circadian time signatures of fitness and disease.
AB  - Biological clocks are autonomous anticipatory oscillators that play a critical
      role in the organization and information processing from genome to whole
      organisms. Transformative advances into the clock system have opened insight into
      fundamental mechanisms through which clocks program energy transfer from sunlight
      into organic matter and potential energy, in addition to cell development and
      genotoxic stress response. The identification of clocks in nearly every single
      cell of the body raises questions as to how this gives rise to rhythmic
      physiology in multicellular organisms and how environmental signals entrain
      clocks to geophysical time. Here, we consider advances in understanding how
      regulatory networks emergent in clocks give rise to cell type-specific functions
      within tissues to affect homeostasis.

PMID- 27885005
TI  - Immunity around the clock.
AB  - Immunity is a high-cost, high-benefit trait that defends against pathogens and
      noxious stimuli but whose overactivation can result in immunopathologies and
      sometimes even death. Because many immune parameters oscillate rhythmically with
      the time of day, the circadian clock has emerged as an important gatekeeper for
      reducing immunity-associated costs, which, in turn, enhances organismal fitness.
      This is mediated by interactions between extrinsic environmental cues and the
      intrinsic oscillators of immune cells, which together optimize immune responses
      throughout the circadian cycle. The elucidation of these clock-controlled
      immunomodulatory mechanisms might uncover new approaches for treating infections
      and chronic inflammatory diseases.

PMID- 27885008
TI  - Better health? Prepare to sweat.

PMID- 27885009
TI  - Mega-earthquakes go the flat way.

PMID- 27885007
TI  - Circadian physiology of metabolism.
AB  - A majority of mammalian genes exhibit daily fluctuations in expression levels,
      making circadian expression rhythms the largest known regulatory network in
      normal physiology. Cell-autonomous circadian clocks interact with daily light
      dark and feeding-fasting cycles to generate approximately 24-hour oscillations in
      the function of thousands of genes. Circadian expression of secreted molecules
      and signaling components transmits timing information between cells and tissues.
      Such intra- and intercellular daily rhythms optimize physiology both by managing
      energy use and by temporally segregating incompatible processes. Experimental
      animal models and epidemiological data indicate that chronic circadian rhythm
      disruption increases the risk of metabolic diseases. Conversely, time-restricted
      feeding, which imposes daily cycles of feeding and fasting without caloric
      reduction, sustains robust diurnal rhythms and can alleviate metabolic diseases.
      These findings highlight an integrative role of circadian rhythms in physiology
      and offer a new perspective for treating chronic diseases in which metabolic
      disruption is a hallmark.

PMID- 27885010
TI  - Tuning nanoparticle strain.

PMID- 27885006
TI  - Mechanisms linking circadian clocks, sleep, and neurodegeneration.
AB  - Disruptions of normal circadian rhythms and sleep cycles are consequences of
      aging and can profoundly affect health. Accumulating evidence indicates that
      circadian and sleep disturbances, which have long been considered symptoms of
      many neurodegenerative conditions, may actually drive pathogenesis early in the
      course of these diseases. In this Review, we explore potential cellular and
      molecular mechanisms linking circadian dysfunction and sleep loss to
      neurodegenerative diseases, with a focus on Alzheimer's disease. We examine the
      interplay between central and peripheral circadian rhythms, circadian clock gene
      function, and sleep in maintaining brain homeostasis, and discuss therapeutic
      implications. The circadian clock and sleep can influence a number of key
      processes involved in neurodegeneration, suggesting that these systems might be
      manipulated to promote healthy brain aging.

PMID- 27885011
TI  - Bringing carbon-silicon bonds to life.

PMID- 27885012
TI  - Protecting memories from stress.

PMID- 27885013
TI  - Targeting the ligand in hypophosphatemia.

PMID- 27885014
TI  - Status alters immune function in macaques.

PMID- 27885015
TI  - Making perfect atomic arrays.

PMID- 27885016
TI  - Open sesame!

PMID- 27885017
TI  - Digital reconstruction of human development.

PMID- 27885018
TI  - For cell reprogramming, context matters.

PMID- 27885019
TI  - Increasing viral threats from mosquitoes.

PMID- 27885020
TI  - Continuing the dialog via experiment.

PMID- 27885021
TI  - Cardiac side effect.

PMID- 27885022
TI  - A new direction for breast cancer therapy.

PMID- 27885023
TI  - Ants farming plants.

PMID- 27885024
TI  - THz-driven magnetism goes nonlinear.

PMID- 27885025
TI  - A clean combination of CO and amines.

PMID- 27885026
TI  - Fast action with little effect.

PMID- 27885027
TI  - Mega-earthquakes rupture flat megathrusts.
AB  - The 2004 Sumatra-Andaman and 2011 Tohoku-Oki earthquakes highlighted gaps in our
      understanding of mega-earthquake rupture processes and the factors controlling
      their global distribution: A fast convergence rate and young buoyant lithosphere
      are not required to produce mega-earthquakes. We calculated the curvature along
      the major subduction zones of the world, showing that mega-earthquakes
      preferentially rupture flat (low-curvature) interfaces. A simplified analytic
      model demonstrates that heterogeneity in shear strength increases with curvature.
      Shear strength on flat megathrusts is more homogeneous, and hence more likely to
      be exceeded simultaneously over large areas, than on highly curved faults.

PMID- 27885028
TI  - Direct and continuous strain control of catalysts with tunable battery electrode
      materials.
AB  - We report a method for using battery electrode materials to directly and
      continuously control the lattice strain of platinum (Pt) catalyst and thus tune
      its catalytic activity for the oxygen reduction reaction (ORR). Whereas the
      common approach of using metal overlayers introduces ligand effects in addition
      to strain, by electrochemically switching between the charging and discharging
      status of battery electrodes the change in volume can be precisely controlled to
      induce either compressive or tensile strain on supported catalysts. Lattice
      compression and tension induced by the lithium cobalt oxide substrate of ~5% were
      directly observed in individual Pt nanoparticles with aberration-corrected
      transmission electron microscopy. We observed 90% enhancement or 40% suppression
      in Pt ORR activity under compression or tension, respectively, which is
      consistent with theoretical predictions.

PMID- 27885029
TI  - The ATG conjugation systems are important for degradation of the inner
      autophagosomal membrane.
AB  - In macroautophagy, cytoplasmic contents are sequestered into the double-membrane
      autophagosome, which fuses with the lysosome to become the autolysosome. It has
      been thought that the autophagy-related (ATG) conjugation systems are required
      for autophagosome formation. Here, we found that autophagosomal soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 17
      positive autophagosome-like structures could be generated even in the absence of
      the ATG conjugation systems, although at a reduced rate. These syntaxin 17
      positive structures could further fuse with lysosomes, but degradation of the
      inner autophagosomal membrane was significantly delayed. Accordingly, autophagic
      activity in ATG conjugation-deficient cells was strongly suppressed. We suggest
      that the ATG conjugation systems, which are likely required for the closure
      (i.e., fission) of the autophagosomal edge, are not absolutely essential for
      autolysosome formation but are important for efficient degradation of the inner
      autophagosomal membrane.

PMID- 27885031
TI  - Retrieval practice protects memory against acute stress.
AB  - More than a decade of research has supported a robust consensus: Acute stress
      impairs memory retrieval. We aimed to determine whether a highly effective
      learning technique could strengthen memory against the negative effects of
      stress. To bolster memory, we used retrieval practice, or the act of taking
      practice tests. Participants first learned stimuli by either restudying or
      engaging in retrieval practice. Twenty-four hours later, we induced stress in
      half of the participants and assessed subsequent memory performance. Participants
      who learned by restudying demonstrated the typical stress-related memory
      impairment, whereas those who learned by retrieval practice were immune to the
      deleterious effects of stress. These results suggest that the effects of stress
      on memory retrieval may be contingent on the strength of the memory
      representations themselves.

PMID- 27885030
TI  - Social status alters immune regulation and response to infection in macaques.
AB  - Social status is one of the strongest predictors of human disease risk and
      mortality, and it also influences Darwinian fitness in social mammals more
      generally. To understand the biological basis of these effects, we combined
      genomics with a social status manipulation in female rhesus macaques to
      investigate how status alters immune function. We demonstrate causal but largely
      plastic social status effects on immune cell proportions, cell type-specific gene
      expression levels, and the gene expression response to immune challenge. Further,
      we identify specific transcription factor signaling pathways that explain these
      differences, including low-status-associated polarization of the Toll-like
      receptor 4 signaling pathway toward a proinflammatory response. Our findings
      provide insight into the direct biological effects of social inequality on immune
      function, thus improving our understanding of social gradients in health.

PMID- 27885034
TI  - Family-friendly science.

PMID- 27885035
TI  - Science fiction and the medical humanities.
AB  - Research on science fiction within the medical humanities should articulate
      interpretative frameworks that do justice to medical themes within the genre.
      This means challenging modes of reading that encourage unduly narrow accounts of
      science fiction. Admittedly, science studies has moved away from reading science
      fiction as a variety of scientific popularisation and instead understands science
      fiction as an intervention in the technoscientific imaginary that calls for
      investment in particular scientific enterprises, including various biomedical
      technologies. However, this mode of reading neglects science fiction's critical
      relationship to the construction of 'the future' in the present: the ways in
      which science fiction proposes concrete alternatives to hegemonic narratives of
      medical progress and fosters critical self-awareness of the contingent activity
      which gives 'the future' substance in the here-and-now. Moreover, the future
      orientation of science fiction should not distract from the function of medical
      science fiction as 'cognitive estrangement': the technological innovations that
      dominate science-fiction narratives are less concrete predictions and more
      generic devices that explain in historical time the origins of a marvellous world
      bearing provocative correspondences to our own, everyday reality. The editorial
      concludes with a series of introductions to the articles comprising the special
      issue, covering the print edition and a special online-only section.

PMID- 27885032
TI  - Directed evolution of cytochrome c for carbon-silicon bond formation: Bringing
      silicon to life.
AB  - Enzymes that catalyze carbon-silicon bond formation are unknown in nature,
      despite the natural abundance of both elements. Such enzymes would expand the
      catalytic repertoire of biology, enabling living systems to access chemical space
      previously only open to synthetic chemistry. We have discovered that heme
      proteins catalyze the formation of organosilicon compounds under physiological
      conditions via carbene insertion into silicon-hydrogen bonds. The reaction
      proceeds both in vitro and in vivo, accommodating a broad range of substrates
      with high chemo- and enantioselectivity. Using directed evolution, we enhanced
      the catalytic function of cytochrome c from Rhodothermus marinus to achieve more
      than 15-fold higher turnover than state-of-the-art synthetic catalysts. This
      carbon-silicon bond-forming biocatalyst offers an environmentally friendly and
      highly efficient route to producing enantiopure organosilicon molecules.

PMID- 27885036
TI  - Visionary medicine: speculative fiction, racial justice and Octavia Butler's
      'Bloodchild'.
AB  - Medical students across the USA have increasingly made the medical institution a
      place for speculating racially just futures. From die-ins in Fall 2014 to silent
      protests in response to racially motivated police brutality, medical schools have
      responded to the public health crisis that is racial injustice in the USA.
      Reading science fiction may benefit healthcare practitioners who are already
      invested in imagining a more just, healthier futurity. Fiction that rewrites the
      future in ways that undermine contemporary power regimes has been termed
      'visionary fiction'. In this paper, the authors introduce 'visionary medicine' as
      a tool for teaching medical students to imagine and produce futures that preserve
      health and racial justice for all. This essay establishes the connections between
      racial justice, medicine and speculative fiction by examining medicine's racially
      unjust past practices, and the intersections of racial justice and traditional
      science and speculative fiction. It then examines speculative fiction author
      Octavia Butler's short story 'Bloodchild' as a text that can introduce students
      of the medical humanities to a liberatory imagining of health and embodiment, one
      that does not reify and reinscribe boundaries of difference, but reimagines the
      nature of Self and Other, power and collaboration, agency and justice.

PMID- 27885037
TI  - The psychologist, the psychoanalyst and the 'extraordinary child' in postwar
      British science fiction.
AB  - A sudden influx of portrayals of 'extraordinary children' emerged in British
      science fiction after the Second World War. Such children both violated and
      confirmed the new set of expectations about ordinary childhood that emerged from
      the findings of developmental psychologists around the same time. Previous work
      on extraordinary children in both science fiction and horror has tended to
      confine the phenomenon to an 'evil child boom' within the American filmmaking
      industry in the 1970s. This article suggests that a much earlier trend is visible
      in British postwar science fiction texts, analysing a cluster of novels that
      emerged in the 1950s: Arthur C. Clarke's Childhood's End (1953), William
      Golding's Lord of the Flies (1954) and John Wyndham's The Midwich Cuckoos (1957).
      It will be argued that the groups of extraordinary children in these novels both
      tap into newer child-centred assertions about the threats posed by abnormal
      childhood, underwritten by psychology and psychoanalysis, and represent a
      reaction to an older progressive tradition in which children were envisaged as
      the single hope for a utopian future. This article will ultimately assert that
      the sudden appearance of extraordinary children in science fiction reflects a
      profound shift in assessment criteria for healthy childhood in Britain from the
      1950s onwards, an issue that had become vitally important in a fledgling social
      democracy.

PMID- 27885038
TI  - Design, fiction and the medical humanities.
AB  - This paper sets out to explore the similarities between the developing discipline
      of speculative and critical design (SCD) and science fiction, and their relevance
      to the medical humanities. SCD looks beyond 'commercial design' to consider what
      sort of things we should, or should not, be designing in order to create
      preferable futures. It does so by extrapolating from current social, economic,
      political and scientific knowledge, designing artefacts, experiences and
      scenarios which communicate futures and alternative realities in tangible ways.
      By first outlying the relevance of SCD to the medical humanities, through its
      ability to imagine and visualise preferable healthcare futures, the paper will
      then discuss several recent design projects which focus on current and future
      ethical issues raised by emerging biotechnology. Through these projects, the
      paper will look at SCD's ability to provoke, engage and critique science and
      society, while also critically reflecting on the limitations of the evolving
      design discipline. Through the paper it is hoped that there can be an increased
      understanding of SCD and its ambitions, as well as its limitations, in order for
      SCD to better approach issues relating to health and wellbeing, along with other
      difficult and challenging issues which will affect all us today and into the (sci
      fi) future.

PMID- 27885039
TI  - Th17 cell frequency and IL-17A concentrations in peripheral blood mononuclear
      cells and vitreous fluid from patients with diabetic retinopathy.
AB  - Objective To quantify T helper (Th)17 cells and determine interleukin (IL)-17A
      levels in peripheral blood mononuclear cell (PBMC) culture and vitreous fluid
      from patients with type 2 diabetes mellitus (T2DM) with diabetic retinopathy
      (DR). Methods Th17 cell frequency and IL-17A concentrations in PBMCs from 60
      patients with T2DM with DR, 30 without DR and 30 sex- and age-matched healthy
      individuals were measured by flow cytometry and enzyme-linked immunosorbent assay
      (ELISA), respectively. IL-17A levels in vitreous fluid from 31 eyes with
      proliferative DR and diabetic macular oedema (DR group) and 32 eyes with an
      epiretinal membrane and macular hole (control group) that underwent vitrectomy
      were also examined by ELISA. Results Compared with the control group, the
      proportion of Th17 cells and IL-17A concentrations in PBMCs were significantly
      increased in patients without DR but decreased in those with DR. IL-17A
      concentrations and Th17 cell frequency in PBMCs tended to decrease with DR
      severity and were negatively correlated with body mass index, T2DM duration and
      glycated haemoglobin. Additionally, vitreous fluid IL-17A levels were
      significantly elevated in patients with DR compared with those of the control
      group. Conclusions We conclude that disturbances in Th17 cells and IL-17A levels
      are possibly associated with DR.

PMID- 27885041
TI  - Pigeons use distinct stop phases to control pecking.
AB  - Pecking at small targets requires accurate spatial coordination of the head.
      Planning of the peck has been proposed to occur in two distinct stop phases, but
      although this idea has now been around for a long time, the specific functional
      roles of these stop phases remain unsolved. Here, we investigated the
      characteristics of the two stop phases using high-speed motion capture and
      examined their functions with two experiments. In experiment 1, we tested the
      hypothesis that the second stop phase is used to pre-program the final approach
      to a target and analyzed head movements while pigeons (Columba livia) pecked at
      targets of different size. Our results show that the duration of both stop phases
      significantly increased as stimulus size decreased. We also found significant
      positive correlations between stimulus size and the distances of the beaks to the
      stimulus during both stop phases. In experiment 2, we used a two-alternative
      forced choice task with different levels of difficulty to test the hypothesis
      that the first stop phase is used to decide between targets. The results indicate
      that the characteristics of the stop phases do not change with an increasing
      difficulty between the two choices. Therefore, we conclude that the first stop
      phase is not exclusively used to decide upon a target to peck at, but also
      contributes to the function of the second stop phase, which is improving pecking
      accuracy and planning the final approach to the target.

PMID- 27885042
TI  - Evidence for partial overlap of male olfactory cues in lampreys.
AB  - Animals rely on a mosaic of complex information to find and evaluate mates.
      Pheromones, often consisting of multiple components, are considered to be
      particularly important for species-recognition in many species. Although the
      evolution of species-specific pheromone blends is well described in many insects,
      very few vertebrate pheromones have been studied in a macro-evolutionary context.
      Here, we report a phylogenetic comparison of multi-component male odours that
      guide reproduction in lampreys. Chemical profiling of sexually mature males from
      eleven species of lamprey, representing six of ten genera and two of three
      families, indicated that the chemical profiles of sexually mature male odours are
      partially shared among species. Behavioural assays conducted with four species
      sympatric in the Laurentian Great Lakes indicated asymmetric female responses to
      heterospecific odours, where Petromyzon marinus were attracted to male odour
      collected from all species tested, but other species generally preferred only the
      odour of conspecifics. Electro-olfactogram recordings from P. marinus indicated
      that although P. marinus exhibited behavioural responses to odours from males of
      all species, at least some of the compounds that elicited olfactory responses
      were different in conspecific male odours compared with heterospecific male
      odours. We conclude that some of the compounds released by sexually mature males
      are shared among species and elicit olfactory and behavioural responses in P.
      marinus, and suggest that our results provide evidence for partial overlap of
      male olfactory cues among lampreys. Further characterization of the chemical
      identities of odour components is needed to confirm shared pheromones among
      species.

PMID- 27885040
TI  - Development and application of a fluorescence protein microarray for detecting
      serum alpha-fetoprotein in patients with hepatocellular carcinoma.
AB  - Objective To develop a simple, effective, time-saving and low-cost fluorescence
      protein microarray method for detecting serum alpha-fetoprotein (AFP) in patients
      with hepatocellular carcinoma (HCC). Method Non-contact piezoelectric print
      techniques were applied to fluorescence protein microarray to reduce the cost of
      prey antibody. Serum samples from patients with HCC and healthy control subjects
      were collected and evaluated for the presence of AFP using a novel fluorescence
      protein microarray. To validate the fluorescence protein microarray, serum
      samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA).
      Results A total of 110 serum samples from patients with HCC ( n = 65) and healthy
      control subjects ( n = 45) were analysed. When the AFP cut-off value was set at
      20 ng/ml, the fluorescence protein microarray had a sensitivity of 91.67% and a
      specificity of 93.24% for detecting serum AFP. Serum AFP quantified via
      fluorescence protein microarray had a similar diagnostic performance compared
      with ELISA in distinguishing patients with HCC from healthy control subjects
      (area under receiver operating characteristic curve: 0.906 for fluorescence
      protein microarray; 0.880 for ELISA). Conclusion A fluorescence protein
      microarray method was developed for detecting serum AFP in patients with HCC.

PMID- 27885043
TI  - Aedes aegypti Rhesus glycoproteins contribute to ammonia excretion by larval anal
      papillae.
AB  - In larval Aedes aegypti, transcripts of the Rhesus-like glycoproteins AeRh50-1
      and AeRh50-2 have been detected in the anal papillae, sites of ammonia (NH3/NH4+)
      excretion; however, these putative ammonia transporters have not been previously
      localized or functionally characterized. In this study, we show that the AeRh50s
      co-immunolocalize with apical V-type H+-ATPase as well as with basal Na+/K+
      ATPase in the epithelium of anal papillae. The double-stranded RNA-mediated
      knockdown of AeRh50-1 and AeRh50-2 resulted in a significant reduction in AeRh50
      protein abundance in the anal papillae, and this was coupled to decreased ammonia
      excretion. The knockdown of AeRh50-1 resulted in decreased hemolymph [NH4+] and
      pH whereas knockdown of AeRh50-2 had no effect on these parameters. We conclude
      that the AeRh50s are important contributors to ammonia excretion at the anal
      papillae of larval A. aegypti, which may be the basis for their ability to
      inhabit areas with high ammonia levels.

PMID- 27885045
TI  - How Canada's Asbestos Industry Was Defeated in Quebec.
AB  - Less than a decade ago, the Quebec asbestos industry enjoyed support from all the
      political parties in the Canadian House of Commons and the Quebec National
      Assembly, as well as from business and union organizations. Two lobby
      organizations (Chrysotile Institute and International Chrysotile Association) had
      significant global impact in promoting asbestos use and defeating asbestos ban
      efforts in developing countries. Quebec's two asbestos mines planned to expand
      operations and make Quebec the second biggest global asbestos exporter. With the
      aid of lobbyists, public relations consultants, and government financing, the
      asbestos industry came close to succeeding. The article examines how a campaign
      of international solidarity, involving scientific experts, asbestos victims, and
      health activists in Quebec, Canada, and overseas, succeeded in closing the two
      mines and defeating the political and social power that the Quebec asbestos
      industry had wielded for a century. This victory ended Canada's destructive role
      as global propagandist for the asbestos industry.

PMID- 27885044
TI  - Blood clotting behavior is innately modulated in Ursus americanus during early
      and late denning relative to summer months.
AB  - Remarkably, American black bears (Ursus americanus) are capable of varying their
      heart rates to coincide with their breathing, creating pauses of 30 s or more,
      yet they do not appear to suffer from embolic events. We evaluated some features
      of the clotting cascade of black bears, providing novel insights into the
      underlying mechanisms they evoke for embolic protection during hibernation. We
      measured activated clotting time, prothrombin time and activated partial
      thromboplastin time during early denning (December), late denning (March) and
      summer (August). Activated clotting time during early hibernation was ~3 times
      longer than that observed among non-hibernating animals. Clotting time was
      reduced later in hibernation, when bears were within ~1 month of emerging from
      dens. Prothrombin time was similar for each seasonal time point, whereas
      activated partial thromboplastin time was highest during early denning and
      decreased during late denning and summer. We also examined D-dimer concentration
      to assess whether the bears were likely to have experienced embolic events. None
      of the non-parturient bears exceeded a D-dimer concentration of 250 ng ml-1
      (considered the clinical threshold for embolism in mammals). Our findings suggest
      there is unique expression of the clotting cascade in American black bears during
      hibernation, in which extrinsic pathways are maintained but intrinsic pathways
      are suppressed. This was evaluated by a significant difference between the
      activated clotting time and activated partial thromboplastin time during the
      denning and non-denning periods. These changes are likely adaptive, to avoid
      clotting events during states of immobilization and/or periods of asystole.
      However, an intact extrinsic pathway allows for healing of external injuries
      and/or foreign body responses.

PMID- 27885046
TI  - The role of basic psychological need satisfaction, sleep, and mindfulness in the
      health-related quality of life of people living with HIV.
AB  - Research has not yet examined the relationship between psychological need
      satisfaction, sleep, mindfulness, and health-related quality of life in people
      living with HIV. This cross-sectional study ( N = 101; 84% male; mean age =
      45.48, SD = 12.75) found need satisfaction to relate positively to physical and
      mental health. Sleep quality fully mediated the association with physical health
      and partially mediated the association with mental health. Furthermore,
      mindfulness related to higher sleep quality through higher need satisfaction.
      Findings underscore the role of need satisfaction in determining health-related
      quality of life and sleep quality in people living with HIV and suggest that
      mindfulness may facilitate need satisfaction.

PMID- 27885047
TI  - Morphological variability of the arterial valve in common arterial trunk and the
      concept of normality.
AB  - OBJECTIVE: Until now, no study established a morphometric evaluation of the
      truncal valve dysplasia and a description of its different presentation patterns.
      Thus, authors conducted an anatomopathological study describing the gross
      features and histological findings of the truncal valve. METHODS: 50 common
      arterial trunk (CAT) specimens were examined. The number of valvar leaflets was
      determined and valvar dysplasia was classified as absent, mild, moderate or
      severe. Selected leaflets were sectioned and submitted to histological analysis
      and linear measurements (thickness, length and area), besides quantification of
      collagen area fraction. RESULTS: 28 (56%) valves presented three, 15 (30%) four
      and 7 (14%) two leaflets. Valvar dysplasia was absent in 13 (26%) cases, mild in
      19 (38%), moderate in 6 (12%) and severe in 12 (24%). A significant association
      was found between the presence of four leaflets and valvar dysplasia (p<0.001).
      Single coronary ostium was more common in two-leaflet cases than in three-leaflet
      cases (p=0.037). Leaflets medial thirds were thicker in the more dysplastic
      valves (p=0.006) and in those presenting anarchic collagen distribution
      (p=0.002). CONCLUSIONS: CAT semilunar valves present two main patterns. The first
      characterised by three leaflets and absent or mild dysplasia and the second by
      four leaflets and severe dysplasia. Still, great variability regarding thickness,
      microscopic organisation of the extracellular matrix and proportions of leaflets'
      dimensions exists, which may impact on the surgical outcomes.

PMID- 27885048
TI  - Trends in educational inequalities in premature mortality in Belgium between the
      1990s and the 2000s: the contribution of specific causes of deaths.
AB  - BACKGROUND: Reducing socioeconomic inequalities in mortality, a key public health
      objective may be supported by a careful monitoring and assessment of the
      contributions of specific causes of death to the global inequality. METHODS: The
      1991 and 2001 Belgian censuses were linked with cause-of-death data, each
      yielding a study population of over 5 million individuals aged 25-64, followed up
      for 5 years. Age-standardised mortality rates (ASMR) were computed by educational
      level (EL) and cause. Inequalities were measured through rate differences (RDs),
      rate ratios (RRs) and population attributable fractions (PAFs). We analysed
      changes in educational inequalities between the 1990s and the 2000s, and
      decomposed the PAF into the main causes of death. RESULTS: All-cause and
      avoidable ASMR decreased in all ELs and both sexes. Lung cancer, ischaemic heart
      disease (IHD), chronic obstructive pulmonary disease (COPD) and suicide in men,
      and IHD, stroke, lung cancer and COPD in women had the highest impact on
      population mortality. RDs decreased in men but increased in women. RRs and PAFs
      increased in both sexes, albeit more in women. In men, the impact of lung cancer
      and COPD inequalities on population mortality decreased while that of suicide and
      IHD increased. In women, the impact of all causes except IHD increased.
      CONCLUSION: Absolute inequalities decreased in men while increasing in women;
      relative inequalities increased in both sexes. The PAFs decomposition revealed
      that targeting mortality inequalities from lung cancer, IHD, COPD in both sexes,
      suicide in men and stroke in women would have the largest impact at population
      level.

PMID- 27885049
TI  - Residential segregation and mental health among Latinos in a nationally
      representative survey.
AB  - BACKGROUND: Among Latinos, living in a locality with greater Latino ethnic
      density may be protective for mental health, although findings vary by Latino
      subgroup, gender and birthplace. Although little studied, Latino residential
      segregation may capture different pathways linking risk and protective
      environmental factors to mental health than local ethnic density. METHODS: This
      study evaluated the association between residential segregation and mental
      distress as measured by the Kessler-10 (K10) among Latino participants in the
      National Latino and Asian American Study (NLAAS). Census data from 2000 was used
      to calculate metropolitan statistical area (MSA) residential segregation using
      the dissimilarity and isolation indices, as well as census tract ethnicity
      density and poverty. Latino subgroup (Puerto Rican, Mexican American, Cuban
      American and other Latino subgroup), gender and generation status were evaluated
      as moderators. RESULTS: Among 2554 Latino participants in NLAAS, residential
      segregation as measured by the isolation index was associated with less mental
      distress (beta -0.14, 95% CI -0.26 to -0.03 log(K10)) among Latinos overall after
      adjustment for ethnic density, poverty and individual covariates. Residential
      segregation as measured by the dissimilarity index was significantly associated
      with less mental distress among men (beta -0.56, 95% CI -1.04 to -0.08) but not
      among women (beta -0.20, 95% CI -0.45 to 0.04, p-interaction=0.019). No
      modification was observed by Latino subgroup or generation. CONCLUSIONS: Among
      Latinos, increasing residential segregation was associated with less mental
      distress, and this association was moderated by gender. Findings suggest that MSA
      level segregation measures may capture protective effects associated with living
      in Latino communities for mental health.

PMID- 27885051
TI  - Linear-rank testing of a non-binary, responder-analysis, efficacy score to
      evaluate pharmacotherapies for substance use disorders.
AB  - The design of pharmacological trials for management of substance use disorders is
      shifting toward outcomes of successful individual-level behavior (abstinence or
      no heavy use). While binary success/failure analyses are common, McCann and Li
      (CNS Neurosci Ther 2012; 18: 414-418) introduced "number of beyond-threshold
      weeks of success" (NOBWOS) scores to avoid dichotomized outcomes. NOBWOS scoring
      employs an efficacy "hurdle" with values reflecting duration of success. Here, we
      evaluate NOBWOS scores rigorously. Formal analysis of mathematical structure of
      NOBWOS scores is followed by simulation studies spanning diverse conditions to
      assess operating characteristics of five linear-rank tests on NOBWOS scores.
      Simulations include assessment of Fisher's exact test applied to hurdle
      component. On average, statistical power was approximately equal for five linear
      rank tests. Under none of conditions examined did Fisher's exact test exhibit
      greater statistical power than any of the linear-rank tests. These linear-rank
      tests provide good Type I and Type II error control for comparing distributions
      of NOBWOS scores between groups (e.g. active vs. placebo). All methods were
      applied to re-analyses of data from four clinical trials of differing lengths and
      substances of abuse. These linear-rank tests agreed across all trials in
      rejecting (or not) their null (equality of distributions) at <= 0.05.

PMID- 27885052
TI  - Enhanced protective responses to a serotype-independent pneumococcal vaccine when
      combined with an inactivated influenza vaccine.
AB  - Streptococcus pneumoniae and influenza are the world's foremost bacterial and
      viral respiratory pathogens. We have previously described a gamma-irradiated
      influenza A virus (gamma-FLU) vaccine that provides cross-protective immunity
      against heterosubtypic infections. More recently, we reported a novel non
      adjuvanted gamma-irradiated S pneumoniae (gamma-PN) vaccine that elicits serotype
      independent protection. Considering the clinical synergism of both pathogens,
      combination of a serotype-independent pneumococcal vaccine with a broad-spectrum
      influenza vaccine to protect against both infections would have a considerable
      clinical impact. In the present study, we co-immunized C57BL/6 mice intranasally
      (IN) with a mixture of gamma-PN (whole inactivated cells) and gamma-FLU (whole
      inactivated virions) and examined protective efficacy. Co-immunization enhanced
      gamma-PN vaccine efficacy against virulent pneumococcal challenge, which was
      dependent on CD4+ T-cell responses. In contrast, vaccination with gamma-PN alone,
      co-immunization enhanced pneumococcal-specific effector T-helper 17 cell (Th17)
      and Th1 memory cell, promoted development of CD4+ tissue-resident memory (TRM)
      cells and enhanced Pneumococcus-specific antibody responses. Furthermore, co
      immunization elicited significant protection against lethal influenza challenge,
      as well as against co-infection with both influenza and S pneumoniae. This is the
      first report showing the synergistic effect of combining whole cell and whole
      virion vaccines to both S pneumoniae and influenza as a single vaccine to protect
      against individual and co-infection, without compromising pathogen-specific
      immunity.

PMID- 27885050
TI  - Cross-sectional and longitudinal associations of neighbourhood social environment
      and smoking behaviour: the multiethnic study of atherosclerosis.
AB  - BACKGROUND: Social features of neighbourhood environments may influence smoking
      by creating a stressful environment or by buffering stress through social
      cohesion. However, the association of the overall neighbourhood social
      environment (NSE) with smoking, and the association of specific neighbourhood
      social factors with change in smoking behaviour over time, has rarely been
      examined. METHODS: This study included 5856 adults aged 45-84 years from the
      Multi-Ethnic Study of Atherosclerosis (2000-2012, average follow-up: 7.8 years).
      Outcomes included current smoking status and smoking intensity (average number of
      cigarettes smoked per day among baseline smokers). NSE was assessed as a
      composite score composed of aesthetic quality, safety and social cohesion scales
      (derived from neighbourhood surveys). Generalised linear mixed models evaluated
      the association of baseline NSE (composite score and individual scales) with
      current smoking (modified Poisson models) and smoking intensity (negative
      binomial models) cross-sectionally and longitudinally. RESULTS: Each SD increase
      in baseline NSE composite score was associated with 13% lower prevalence of
      smoking at baseline (adjusted prevalence ratio (aPR) 0.87 (95% CI 0.78 to 0.98).
      Neighbourhood safety and aesthetic quality were similarly associated with lower
      smoking prevalence (aPR 0.87 (0.78 to 0.97) and aPR 0.87 (0.77 to 0.99),
      respectively) but the association with social cohesion was weaker or null. No
      significant associations were observed for smoking intensity among baseline
      smokers. Baseline NSE was not associated with changes in smoking risk or
      intensity over time. CONCLUSIONS: Results suggest that neighbourhood social
      context influences whether older adults smoke, but does not promote smoking
      cessation or reduction over time.

PMID- 27885053
TI  - 11beta-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome
      response to Western diet.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconverts active
      glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme,
      11beta-HSD1, predominantly reactivates glucocorticoids in vivo and can also
      metabolise bile acids. 11beta-HSD1-deficient mice show altered inflammatory
      responses and are protected against the adverse metabolic effects of a high-fat
      diet. However, the impact of 11beta-HSD1 on the composition of the gut microbiome
      has not previously been investigated. We used high-throughput 16S rDNA amplicon
      sequencing to characterise the gut microbiome of 11beta-HSD1-deficient and
      C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat
      enriched 'Western' diet. 11beta-HSD1 deficiency significantly altered the
      composition of the gut microbiome, and did so in a diet-specific manner. On a
      Western diet, 11beta-HSD1 deficiency increased the relative abundance of the
      family Bacteroidaceae, and on a chow diet, it altered relative abundance of the
      family Prevotellaceae Our results demonstrate that (i) genetic effects on host
      microbiome interactions can depend upon diet and (ii) that alterations in the
      composition of the gut microbiome may contribute to the aspects of the metabolic
      and/or inflammatory phenotype observed with 11beta-HSD1 deficiency.

PMID- 27885054
TI  - Impact of uteroplacental insufficiency on postnatal rat male gonad.
AB  - Prenatal events such as intrauterine growth restriction can affect gonadal
      development of the offspring and have an impact on reproductive health. To
      investigate the effects of intrauterine growth restriction induced by uterine
      artery ligation on the postnatal rat testis. Pregnant rats underwent uterine
      artery ligation at day 19 of gestation. Offspring were killed at 5, 20 and 40
      days post-partum (dpp). At killing, one gonad was snap-frozen in liquid nitrogen
      and processed for RNA and steroid extraction. The other gonad was formalin-fixed
      for histology. Gene expression was analyzed by TaqMan Low-Density Array.
      Intratesticular testosterone, estradiol and serum gonadotrophins were measured.
      Thirty genes were dysregulated in intrauterine growth-restricted rats compared to
      controls, among which markers of Sertoli cell and Leydig cell function, cell
      metabolism and growth factors. Testis weights were significantly reduced at 5 and
      20 dpp in intrauterine growth-restricted rats and caught-up by 40 dpp
      Accordingly, Sertoli cell number was significantly lower in 5 dpp intrauterine
      growth-restricted rats. At 20 dpp, intratesticular testosterone was significantly
      increased in intrauterine growth-restricted rats, whereas serum gonadotrophins
      were unchanged. IUGR altered the gene expression in the rat testes up to
      peripubertal age and reduced testis size and Sertoli cell number in neonatal age.
      Multiple mechanisms encompassing genetic changes and steroid production by the
      testis may be involved in the catch-up growth phase that restored testis size by
      40 dpp Permanent consequences on organ function and gamete integrity cannot be
      excluded and deserve further investigations.

PMID- 27885055
TI  - 17beta-estradiol improves hepatic mitochondrial biogenesis and function through
      PGC1B.
AB  - Sexual dimorphism in mitochondrial biogenesis and function has been described in
      many rat tissues, with females showing larger and more functional mitochondria.
      The family of the peroxisome proliferator-activated receptor gamma coactivator 1
      (PGC1) plays a central role in the regulatory network governing mitochondrial
      biogenesis and function, but little is known about the different contribution of
      hepatic PGC1A and PGC1B in these processes. The aim of this study was to
      elucidate the role of 17beta-estradiol (E2) in mitochondrial biogenesis and
      function in liver and assess the contribution of both hepatic PGC1A and PGC1B as
      mediators of these effects. In ovariectomized (OVX) rats (half of which were
      treated with E2) estrogen deficiency led to impaired mitochondrial biogenesis and
      function, increased oxidative stress, and defective lipid metabolism, but was
      counteracted by E2 treatment. In HepG2 hepatocytes, the role of E2 in enhancing
      mitochondrial biogenesis and function was confirmed. These effects were
      unaffected by the knockdown of PGC1A, but were impaired when PGC1B expression was
      knocked down by specific siRNA. Our results reveal a widespread protective role
      of E2 in hepatocytes, which is explained by enhanced mitochondrial content and
      oxidative capacity, lower hepatic lipid accumulation, and a reduction of
      oxidative stress. We also suggest a novel hepatic protective role of PGC1B as a
      modulator of E2 effects on mitochondrial biogenesis and function supporting
      activation of PGC1B as a therapeutic target for hepatic mitochondrial disorders.

PMID- 27885056
TI  - Understanding the functions and operations of data monitoring committees: Survey
      and focus group findings.
AB  - BACKGROUND: The use of data monitoring committees in the conduct of clinical
      trials has increased and evolved, but there is a lack of published information on
      when data monitoring committees are needed and utilized, the acceptable range of
      data monitoring committee practices, and appropriate qualifications of data
      monitoring committee members. METHODS: To gain a better understanding of data
      monitoring committee operations and areas for improvement, the Clinical Trials
      Transformation Initiative conducted a survey and set of focus groups. A total of
      143 respondents completed the online survey: 76 data monitoring committee
      members, 52 sponsors involved with organization of data monitoring committees,
      and 15 statistical data analysis center representatives. There were 42 focus
      group participants, including data monitoring committee members; patients and/or
      patient advocate data monitoring committee members; institutional review board
      and US Food and Drug Administration representatives; industry, government, and
      non-profit sponsors; and statistical data analysis center representatives.
      RESULTS: Participants indicated that the primary responsibility of a data
      monitoring committee is to be an independent advisory body representing the
      interests of trial participants by assessing the risk and benefit ratio in
      ongoing trials. They noted that data monitoring committees must have access to
      unmasked data in order to perform this role. No clear consensus emerged regarding
      specific criteria for requiring a data monitoring committee for a given trial,
      and some participants felt data monitoring committees may be overused.
      Respondents offered suggestions for the data monitoring committee charter and
      communications with sponsors, institutional review boards, and regulators.
      Overall, data monitoring committee members reported that they are able to
      function independently and their recommendations are almost always accepted by
      the sponsor. Participants indicated that there are no standards or guidelines
      pertaining to qualifications of data monitoring committee members. Furthermore,
      only 8% (6/72) of data monitoring committee member survey respondents received
      any formal training, and 94% (68/72) were not aware of any training programs.
      CONCLUSION: Findings from the survey and focus groups provide a better
      understanding of contemporary data monitoring committee operations and insights
      regarding challenges and best practices. Overall, it was clear that increased
      training will be needed to prepare the next generation of qualified data
      monitoring committee members to meet the growing demand. These findings can be
      used by Clinical Trials Transformation Initiative and others to develop
      recommendations and tools to improve data monitoring committee operations and the
      overall quality of trial oversight.

PMID- 27885057
TI  - Circulating active serum calcium reduces the risk of hypertension.
AB  - Purpose Calcium, which is one the most abundant mineral elements in the body, has
      been suggested to be involved in blood pressure regulation. We aimed to assess
      the association of active serum calcium (which is the ionised and physiologically
      active form of serum calcium) with the future risk of hypertension. Methods The
      active serum calcium concentration was assessed at baseline in the Finnish Kuopio
      Ischemic Heart Disease population-based prospective cohort study of 1562
      normotensive men aged 42-61 years at baseline. Cox proportional hazard models
      were used to assess the hazard ratios (95% confidence intervals (CIs)) for
      incident hypertension. Results During a median follow-up of 24.9 years, 247 men
      developed new-onset hypertension. Active serum calcium was inversely associated
      with incident hypertension in an approximately linear fashion. In age-adjusted
      analysis, the hazard ratio for hypertension per 1 standard deviation increase in
      active serum calcium was 0.86 (95% CI 0.76-0.98), which remained consistent after
      adjustment for several established risk factors and potential confounders 0.82
      (0.71-0.94). In a comparison of extreme quintiles of active serum calcium levels,
      the corresponding adjusted hazard ratios were 0.59 (95% CI 0.39-0.90) and 0.54
      (95% CI 0.35-0.82), respectively. Conclusion Active serum calcium is protective
      of future hypertension in a middle-aged male Caucasian population. Further
      research is needed to confirm these findings and help unravel the mechanistic
      pathways of calcium in the pathogenesis of hypertension.

PMID- 27885058
TI  - Association between human immunodeficiency virus infection and arterial stiffness
      in children.
AB  - Background Human immunodeficiency virus infection (HIV) is associated with
      increased cardiovascular risk and adverse cardiovascular outcome in adults. Early
      recognition of changes in vascular properties might prove essential in
      cardiovascular prevention in HIV-infected patients. We investigated the relations
      between HIV infection and arterial stiffness in children. Methods This cross
      sectional study included 51 HIV-infected and 52 healthy children (age 3.2-14.5
      years, 49 males). All infected children had acquired HIV by vertical transmission
      and were receiving antiretroviral therapy at time of assessment. Arterial
      stiffness was measured by pulse wave velocity and aortic augmentation index,
      using the Arteriograph system (Tensiomed Kft, Budapest, Hungary). We applied
      multivariable general linear modeling to evaluate the relationship between HIV
      infection and arterial stiffness with further adjustment for confounders and
      possible intermediary variables. Findings represent mean group differences with
      95% confidence intervals and p values. Results Aortic augmentation index was
      higher by 9.0% (5.6-12.5, p < 0.001) in HIV-infected than in healthy children.
      Adjustment for blood pressure, protease inhibitor use, biomarkers for level of
      inflammation, lipid- and glucose-metabolism, as possible intermediary variables,
      did not appreciably alter the results. There were no significant differences in
      pulse wave velocity between HIV-infected and healthy children (mean difference
      0.28 m/s, -0.14-0.69, p = 0.19). Conclusion HIV-infected children have an
      increased aortic augmentation index, compared to healthy children. Early
      cardiovascular assessment may be important in targeted prevention for HIV
      infected children.

PMID- 27885059
TI  - Association of grip strength with cardiovascular risk markers.
AB  - Background Mechanisms underlying the association between grip strength and
      cardiovascular mortality are poorly understood. We aimed to assess the
      association of grip strength with a panel of cardiovascular risk markers. Design
      The study was based on a cross-sectional analysis of 3468 adults aged 50-75 years
      (1891 women) from a population-based sample in Lausanne, Switzerland. Methods
      Grip strength was measured using a hydraulic hand dynamometer. Cardiovascular
      risk markers included anthropometry, blood pressure, lipids, glucose, adiposity,
      inflammatory and other metabolic markers. Results In both genders, grip strength
      was negatively associated with fat mass (Pearson correlation coefficient: women: 
      0.170, men: -0.198), systolic blood pressure (women: -0.096, men: -0.074),
      fasting glucose (women: -0.048, men: -0.071), log-transformed leptin (women: 
      0.074, men: -0.065), log-transformed high-sensitivity C-reactive protein (women: 
      0.101, men: -0.079) and log-transformed homocysteine (women: -0.109, men: 
      0.060). In men, grip strength was also positively associated with diastolic blood
      pressure (0.068), total (0.106) and low density lipoprotein-cholesterol (0.082),
      and negatively associated with interleukin-6 (-0.071); in women, grip strength
      was negatively associated with triglycerides (-0.064) and uric acid (-0.059).
      After multivariate adjustment, grip strength was negatively associated with waist
      circumference (change per 5 kg increase in grip strength: -0.82 cm in women and 
      0.77 cm in men), fat mass (-0.56% in women; -0.27% in men) and high-sensitivity C
      reactive protein (-6.8% in women; -3.2% in men) in both genders, and with body
      mass index (0.22 kg/m2) and leptin (-2.7%) in men. Conclusion Grip strength shows
      only moderate associations with cardiovascular risk markers. The effect of muscle
      strength as measured by grip strength on cardiovascular disease does not seem to
      be mediated by cardiovascular risk markers.

PMID- 27885060
TI  - Gender differences in physical activity following acute myocardial infarction in
      adults: A prospective, observational study.
AB  - Aims Despite the benefits of regular physical activity participation following
      acute myocardial infarction, little is known about gender differences in physical
      activity among patients after acute myocardial infarction. We described, by
      gender, physical activity trajectories pre- and post-acute myocardial infarction,
      and determined whether gender was independently associated with physical
      activity. Methods and results The Variation in Recovery: Role of Gender on
      Outcomes of Young AMI patients (VIRGO) study, conducted at 103 US, 24 Spanish,
      and three Australian hospitals, was designed, in part, to evaluate gender
      differences in lifestyle behaviors following acute myocardial infarction. We used
      baseline, one-month, and 12-month data collected from patients aged 18-55 years (
      n = 3572). Patients were assigned to American Heart Association-defined levels of
      physical activity. A generalized estimating equation model was used to account
      for repeated measures within the same individual over time. Men were more active
      (>=150 min/wk moderate or >=75 min/wk vigorous activity) than women at baseline
      (42% vs 34%), one month (45% vs 34%), and 12 months (48% vs 36%) (all p <
      0.0001). Men engaged in a significantly longer duration of activity at each time
      point. When controlling for all other factors, women had 1.37 times the odds of
      being less active than men from pre-acute myocardial infarction to 12-months post
      acute myocardial infarction (95% confidence interval: 1.21-1.55). Non-white race,
      non-active workplaces, smoking, diabetes, hypertension, and obesity were also
      associated independently with being less active over time (all p < 0.05).
      Conclusions Although activity increased modestly over time, women recovering from
      acute myocardial infarction were less likely to meet physical activity
      recommendations than were men. By identifying factors associated with low levels
      of activity during acute myocardial infarction recovery, targeted interventions
      can be introduced prior to hospital discharge.

PMID- 27885061
TI  - Alemtuzumab improves quality-of-life outcomes compared with subcutaneous
      interferon beta-1a in patients with active relapsing-remitting multiple
      sclerosis.
AB  - BACKGROUND: Alemtuzumab was superior on clinical and magnetic resonance imaging
      (MRI) outcomes versus subcutaneous interferon beta-1a in phase 3 trials in
      patients with relapsing-remitting multiple sclerosis. OBJECTIVE: To examine
      quality-of-life (QoL) outcomes in the alemtuzumab phase 3 trials. METHODS:
      Patients who were treatment naive (Comparison of Alemtuzumab and Rebif(r)
      Efficacy in Multiple Sclerosis I [CARE-MS I]) or had an inadequate response to
      prior therapy (CARE-MS II) received annual courses of alemtuzumab 12 mg/day at
      baseline (5 days) and Month 12 (3 days) or subcutaneous interferon beta-1a 44 ug
      three times/week. QoL was measured every 6 or 12 months using Functional
      Assessment of Multiple Sclerosis (FAMS), European Quality of Life-5 Dimensions
      (EQ-5D) and its visual analog scale (EQ-VAS), and 36-Item Short-Form Survey (SF
      36). RESULTS: Statistically significant improvements from baseline with
      alemtuzumab were observed on all three QoL instruments at the earliest post
      baseline assessment and sustained through Year 2. Statistically significant
      greater QoL improvements over subcutaneous interferon beta-1a were seen at all
      time points in CARE-MS II with FAMS, EQ-VAS and SF-36 physical component summary,
      and in CARE-MS I with FAMS. CONCLUSION: Patients treated with alemtuzumab had
      improvements in physical, mental, and emotional QoL regardless of treatment
      history. Improvements were significantly greater with alemtuzumab versus
      subcutaneous interferon beta-1a on both disease-specific and general measures of
      QoL.

PMID- 27885062
TI  - Quantifying risk of early relapse in patients with first demyelinating events:
      Prediction in clinical practice.
AB  - BACKGROUND: Characteristics at clinically isolated syndrome (CIS) examination
      assist in identification of patient at highest risk of early second attack and
      could benefit the most from early disease-modifying drugs (DMDs). OBJECTIVE: To
      examine determinants of second attack and validate a prognostic nomogram for
      individualised risk assessment of clinical conversion. METHODS: Patients with CIS
      were prospectively followed up in the MSBase Incident Study. Predictors of
      clinical conversion were analysed using Cox proportional hazards regression.
      Prognostic nomograms were derived to calculate conversion probability and
      validated using concordance indices. RESULTS: A total of 3296 patients from 50
      clinics in 22 countries were followed up for a median (inter-quartile range
      (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a
      second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first
      symptom location, oligoclonal bands and various brain and spinal magnetic
      resonance imaging (MRI) metrics were all predictors of conversion. Conversely,
      older age and DMD exposure post-CIS were associated with reduced rates.
      Prognostic nomograms demonstrated high concordance between estimated and observed
      conversion probabilities. CONCLUSION: This multinational study shows that age at
      CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and
      oligoclonal bands are associated with shorter time to relapse. Nomogram
      assessment may be useful in clinical practice for estimating future clinical
      conversion.

PMID- 27885063
TI  - Closing the gap: Longitudinal changes in employment for Australians with multiple
      sclerosis.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have documented far lower employment
      participation rates for people with multiple sclerosis (PwMS) compared to the
      general population. In a large national sample of PwMS, we examined employment
      status, longitudinal changes in employment and the provision of modifications to
      work role/environment from 2010 to 2013. METHODS: Employment data were collected
      through the Australian MS Longitudinal Study from 2010 to 2013, with 1260 people
      responding to all four surveys. Employment rates were compared with the
      Australian general population. The survey included questions on the provision of
      modifications to employees' work role and work environment. RESULTS: Employment
      (full- and part-time) increased from 48.8% in 2010 to 57.8% in 2013, mainly due
      to increases in male full-time employment. The employment gap between PwMS and
      the general population fell from 14.3% in 2010 to 3.5% in 2013. Male employment
      rates, however, remain significantly lower than the general population. The
      majority of PwMS who required adjustments to either their work role or
      environment received them. CONCLUSION: The gap in employment between PwMS and the
      general population has substantially reduced from 2010 to 2013, with
      organisations responding positively to requests for work role/environment
      adjustments.

PMID- 27885064
TI  - Differential effects of aging on motor and cognitive functioning in multiple
      sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) patients are impaired in motor and cognitive
      performance, but the extent to which these deficits are magnified by aging is
      unknown. In one prior study, differences in cognitive processing speed between MS
      patients and healthy individuals were of similar magnitude across the lifespan.
      Here, we have improved on this work by expanding assessment to multiple cognitive
      domains and motor functioning. OBJECTIVE: To determine whether the degree of
      cognitive and motor dysfunction in MS is magnified with increasing age. METHODS:
      In all, 698 MS patients (aged 29-71 years) and 226 healthy controls (HCs; aged 18
      72 years) completed neuroperformance tests covering ambulation, upper extremity
      function, information processing speed, and memory. RESULTS: Linear regression
      models predicting cognitive and motor function revealed main effects of MS/HC
      diagnosis, age, and education across all measures. There was also an interaction
      between age and diagnosis on measures of motor function, but not on cognitive
      outcomes. CONCLUSION: The progression of motor decline is amplified by aging in
      MS. However, the degree of cognitive impairment does not vary across the
      lifespan. Thus, evidence of accelerated cognitive impairment in older adults with
      MS may signal the presence of other age-related cognitive pathologies.

PMID- 27885065
TI  - Effectiveness of mycophenolate mofetil as first-line therapy in AQP4-IgG, MOG
      IgG, and seronegative neuromyelitis optica spectrum disorders.
AB  - OBJECTIVE: To evaluate the effectiveness and tolerance of mycophenolate mofetil
      (MMF) as a first-line treatment in neuromyelitis optica spectrum disorder
      (NMOSD). METHODS: In all, 67 NMOSD patients treated by MMF as first-line therapy,
      from the NOMADMUS cohort were included. A total of 65 fulfilled 2015 NMOSD
      criteria, and 5 were myelin oligodendrocyte glycoprotein (MOG)-immunoglobulin G
      (IgG) positive. Effectiveness was evaluated on percentage of patients continuing
      MMF, percentage of patients free of relapse, pre- and post-treatment change in
      the annualized relapse rate (ARR), and Expanded Disability Status Scale (EDSS).
      RESULTS: Among 67 patients, 40 (59.7%) continued treatment till last follow-up. A
      total of 33 (49.3%) were relapse-free. The median ARR decreased from one pre
      treatment to zero post-treatment. Of 53 patients with complete EDSS data, the
      score improved or stabilized in 44 (83%; p < 0.05). Effectiveness was observed in
      aquaporin-4 (AQP4)-IgG (57.8% continued treatment, 46.7% relapse-free), MOG-IgG
      (3/5 continued treatment, 4/5 relapse-free), and seronegative NMOSD (64.7%
      continued treatment, 61.3% relapse-free). In 16 patients with associated
      steroids, 13 (81.2%) continued MMF till last follow-up versus 15 of 28 (53.6%) in
      the non-steroid group. Nine patients discontinued treatment for tolerability
      purpose. CONCLUSION: MMF showed effectiveness and good tolerability as a first
      line therapy in NMOSD, whatever the AQP4-IgG status. Concomitant use of oral
      steroids at start could limit the risk of treatment failure.

PMID- 27885067
TI  - Repeat infection with Neisseria gonorrhoeae among active duty U.S. Army
      personnel: a population-based case-series study.
AB  - Little information is known on the rate of repeat gonorrhea infection among U.S.
      military personnel. We analyzed all gonorrhea cases reported to the Defense
      Medical Surveillance System during 2006-2012 to determine the rate of repeat
      infection. During the seven-year study period, 17,602 active duty U.S. Army
      personnel with a first incident gonorrhea infection were reported. Among the 4987
      women with a first gonorrhea infection, 14.4% had at least one repeat infection.
      Among the 12,615 men with a first gonorrhea infection, 13.7% had at least one
      repeat infection. Overall, the rate of repeat gonorrhea infection was 44.5 and
      48.9 per 1000 person-years for women and men, respectively. Service members aged
      17-19 years (hazard ratio [HR] for women = 1.51; HR for men = 1.71), African
      American personnel (HR for women = 1.26; HR for men = 2.17), junior enlisted
      personnel (HR for women = 2.64; HR for men = 1.37), and those with one year or
      less of service (HR for women = 1.23; HR for men = 1.37) were at higher risk of
      repeat infection. The findings from this study highlight the need to develop
      targeted prevention initiatives including education, counseling, and retesting to
      prevent gonorrhea reinfections among U.S. Army personnel.

PMID- 27885068
TI  - Facial Redness Increases Men's Perceived Healthiness and Attractiveness.
AB  - Past research has shown that peripheral and facial redness influences perceptions
      of attractiveness for men viewing women. The current research investigated
      whether a parallel effect is present when women rate men with varying facial
      redness. In four experiments, women judged the attractiveness of men's faces,
      which were presented with varying degrees of redness. We also examined perceived
      healthiness and other candidate variables as mediators of the red-attractiveness
      effect. The results show that facial redness positively influences ratings of
      men's attractiveness. Additionally, perceived healthiness was documented as a
      mediator of this effect, independent of other potential mediator variables. The
      current research emphasizes facial coloration as an important feature of social
      judgments.

PMID- 27885069
TI  - Exploring family stigma among caregivers of persons with Alzheimer's disease: The
      experiences of Israeli-Arab caregivers.
AB  - Providing care to persons with Alzheimer's disease poses challenges for spouses
      and adult children, including experiencing stigmatic beliefs towards themselves
      i.e., family stigma. Drawing on the frameworks of ethnicity and stigma and
      ethnicity and dementia, the current study explored stigmatic experiences among
      Israeli Arab family caregivers of a person with Alzheimer's disease. Three focus
      groups with 20 caregivers (adult children and spouses) of persons with
      Alzheimer's disease were conducted. Data were analyzed using theory-led thematic
      analysis. Caregivers reported experiencing family stigma in two dimensions:
      public and affiliate stigma, in both the existence of an attribution process in
      which cognitive stereotypes elicit negative and positive emotions which in turn
      provoke behavioral attributions, was evident. Family stigma was found to be a
      discernible feature of everyday reality among Israeli Arab caregivers of persons
      with Alzheimer's disease and stress the importance of developing management
      strategies that are tailored to the socio-cultural characteristics of the
      caregivers.

PMID- 27885070
TI  - PRUDENCE AND CONSERVATISM IN RADIATION PROTECTION: A CASE STUDY.
AB  - Prudence is a cornerstone of radiation protection philosophy. However, whilst the
      concept is clearly valid at the level of principle, it is nonetheless necessary
      to ask 'How should prudence be applied in the context of various practical
      situations.' This is perhaps particularly important where exposures are low
      within the range of natural background, where changes in the level of protection
      will have no meaningful impact whatsoever on the overall exposure level of any
      individual. The concept of prudence is applied at a 'top tier' level through the
      application of the Linear No Threshold hypothesis. In day-to-day protection
      considerations, including many types of dose assessments, the concept of prudence
      has translated into the need to take a conservative approach. This paper
      considers the combined impact of accumulated layers of conservatism, using the
      example of clearance as a case study. It concludes that doses actually resulting
      from the clearance process are typically more than two orders of magnitude below
      the internationally agreed objective of 'some tens of uSv y-1', which was itself
      established on the basis of considerable prudence. The implications of this
      outcome are discussed.

PMID- 27885066
TI  - Effects in dogs with behavioural disorders of a commercial nutraceutical diet on
      stress and neuroendocrine parameters.
AB  - The well-being of dogs can be affected by changes in human lifestyle, eating
      habits and increased stressors that lead to behavioural disorders including fear,
      hyperactivity and anxiety, followed by negative affective moods and poor welfare.
      This randomised, controlled clinical evaluation involved 69 dogs, 38 males and 31
      females, of different breeds, with behavioural disorders related to anxiety and
      chronic stress. They were fed a control diet or a nutraceutical diet (ND group)
      for 45 days. Neuroendocrine (serotonin, dopamine, beta-endorphins, noradrenaline
      and cortisol) and stress (derivatives of reactive oxygen metabolites (dROMs) and
      biological antioxidant potential (BAP)) parameters related to behavioural
      disorders were evaluated at the beginning and end of the study period. Results
      showed a significant increase in serotonin, dopamine and beta-endorphins plasma
      concentrations (*P<0.05, *P<0.05 and **P<0.01, respectively) and a significant
      decrease in noradrenaline and cortisol plasma concentrations in the ND group
      (*P<0.05). dROMs significantly decreased in the ND group (*P<0.05) while BAP was
      not affected. This study demonstrated for the first time that a specific diet
      significantly and positively affected neuroendocrine parameters and dROMs. These
      results open significant perspectives concerning the use of diet and
      nutraceuticals in the treatment of behavioural disorders.

PMID- 27885071
TI  - Certified Training for Nuclear and Radioactive Source Security Management.
AB  - Radioactive sources are used by hospitals, research facilities and industry for
      such purposes as diagnosing and treating illnesses, sterilising equipment and
      inspecting welds. Unfortunately, many States, regulatory authorities and
      licensees may not appreciate how people with malevolent intentions could use
      radioactive sources, and statistics confirm that a number of security incidents
      happen around the globe. The adversary could be common thieves, activists,
      insiders, terrorists and organised crime groups. Mitigating this risk requires
      well trained and competent staff who have developed the knowledge, attributes and
      skills necessary to successfully discharge their security responsibilities. The
      International Atomic Energy Agency and the World Institute for Nuclear Security
      are leading international training efforts. The target audience is a multi
      disciplinary group of professionals with management responsibilities for security
      at facilities with radioactive sources. These efforts to promote training and
      competence amongst practitioners have been recognised at the 2014 and 2016
      Nuclear Security and Nuclear Industry Summits.

PMID- 27885072
TI  - MONTE CARLO CALIBRATION OF THE WHOLE-BODY COUNTING DETECTION SYSTEM FOR IN VIVO
      MEASUREMENT OF PEOPLE INTERNALLY CONTAMINATED WITH 90SR.
AB  - This work is focused on numerical calibrations of the body counter for in vivo
      measurement of pure beta emitters through the produced bremsstrahlung radiation.
      Calibrations were performed using the UPh-02T block whole-body phantom and the
      Lawrence Livermore National Laboratory (LLNL) realistic torso phantom. Neither of
      these physical phantoms is appropriate for such calibrations; therefore, specific
      90Sr sources have been manufactured to be used with the UPh-02T phantom for
      experimental measurement followed with Monte Carlo (MC) simulations. Calibrations
      with the LLNL torso phantom were carried out solely using MC technique. Different
      scenarios of the 90Sr distribution in the human tissues were considered for the
      spectrometer calibrations. MC simulations with the LLNL confirmed the
      applicability of the UPh-02T with specific 90Sr/90Y sources for experimental
      calibrations of the body counters for measurement of pure beta emitters.
      Differences in count rates in 50-200 keV for UPh-02T and LLNL were not >25% for
      all considered scenarios.

PMID- 27885073
TI  - EVALUATION OF EYE LENS DOSES OF INTERVENTIONAL CARDIOLOGISTS.
AB  - The effective dose of medical staff members, especially interventional
      radiologists and cardiologists, is classified as a relatively high level. We
      measured the dose for interventional cardiologists by using optically stimulated
      luminescence dosimeters (OSLDs). However, this quantity is not the same as Hp
      (3). In experiments, the dose at the eye-lens position of a phantom were measured
      using OSLDs and thermoluminescence dosimeters (TLDs). A conversion factor from
      dose measured by using TLDs to OSLDs was estimated from these results. In
      addition, the eye doses of interventional cardiologists in clinical situations
      were measured, and the effect of eyewear on the eye-lens dose was discussed.

PMID- 27885074
TI  - Developing an Optimum Protocol for Thermoluminescence Dosimetry with GR-200 Chips
      using Taguchi Method.
AB  - Thermoluminescence dosimetry (TLD) is a powerful technique with wide applications
      in personal, environmental and clinical dosimetry. The optimum annealing, storage
      and reading protocols are very effective in accuracy of TLD response. The purpose
      of this study is to obtain an optimum protocol for GR-200; LiF: Mg, Cu, P, by
      optimizing the effective parameters, to increase the reliability of the TLD
      response using Taguchi method. Taguchi method has been used in this study for
      optimization of annealing, storage and reading protocols of the TLDs. A number of
      108 GR-200 chips were divided into 27 groups, each containing four chips. The
      TLDs were exposed to three different doses, and stored, annealed and read out by
      different procedures as suggested by Taguchi Method. By comparing the signal-to
      noise ratios the optimum dosimetry procedure was obtained. According to the
      results, the optimum values for annealing temperature ( degrees C), Annealing
      Time (s), Annealing to Exposure time (d), Exposure to Readout time (d), Pre-heat
      Temperature ( degrees C), Pre-heat Time (s), Heating Rate ( degrees C/s), Maximum
      Temperature of Readout ( degrees C), readout time (s) and Storage Temperature (
      degrees C) are 240, 90, 1, 2, 50, 0, 15, 240, 13 and -20, respectively. Using the
      optimum protocol, an efficient glow curve with low residual signals can be
      achieved. Using optimum protocol obtained by Taguchi method, the dosimetry can be
      effectively performed with great accuracy.

PMID- 27885075
TI  - SUITABILITY OF PORTABLE RADIONUCLIDE IDENTIFIERS FOR EMERGENCY INCORPORATION
      MONITORING.
AB  - The suitability of portable nuclide inspectors for incorporation measurements
      were tested with three probes (LaBr3(Ce), NaI(Tl) and HPGe) differing in
      sensitive volume and energy resolution. The efficiencies for the measurement of
      whole-body and lung radionuclide burden were calibrated using a whole-body block
      phantom with traceable radionuclide sources of 60Co, 133Ba, 137Cs, 152Eu and 40K.
      A standing geometry was chosen as it allows rapid positioning of persons for the
      measurements. Decision and detection limits were determined for the unshielded
      detector in a normal laboratory radiation environment according to ISO 11929 for
      134Cs, 137Cs and 60Co. The detection limits of all three probes were
      significantly higher compared to well-shielded dedicated whole-body monitors
      (HPGe and NaI(Tl)) using a sitting geometry. Nevertheless, lung and whole-body
      burdens derived from dose constraints for routine and emergency conditions could
      be measured with all three probes with a counting time of one minute.

PMID- 27885076
TI  - Estimates of Radiation Effects on Cancer Risks in the Mayak Worker, Techa River
      and Atomic Bomb Survivor Studies.
AB  - For almost 50 y, the Life Span Study cohort of atomic bomb survivor studies has
      been the primary source of the quantitative estimates of cancer and non-cancer
      risks that form the basis of international radiation protection standards.
      However, the long-term follow-up and extensive individual dose reconstruction for
      the Russian Mayak worker cohort (MWC) and Techa River cohort (TRC) are providing
      quantitative information about radiation effects on cancer risks that complement
      the atomic bomb survivor-based risk estimates. The MWC, which includes ~26 000
      men and women who began working at Mayak between 1948 and 1982, is the primary
      source for estimates of the effects of plutonium on cancer risks and also
      provides information on the effects of low-dose rate external gamma exposures.
      The TRC consists of ~30 000 men and women of all ages who received low-dose-rate,
      low-dose exposures as a consequence of Mayak's release of radioactive material
      into the Techa River. The TRC data are of interest because the exposures are
      broadly similar to those experienced by populations exposed as a consequence of
      nuclear accidents such as Chernobyl. In this presentation, it is described the
      strengths and limitations of these three cohorts, outline and compare recent
      solid cancer and leukemia risk estimates and discussed why information from the
      Mayak and Techa River studies might play a role in the development and refinement
      of the radiation risk estimates that form the basis for radiation protection
      standards.

PMID- 27885077
TI  - HIGHLIGHTS OF THE RUSSIAN HEALTH STUDIES PROGRAM AND UPDATED RESEARCH FINDINGS.
AB  - Recognized for conducting cutting-edge science in the field of radiation health
      effects research, the Department of Energy's (DOE) Russian Health Studies Program
      has continued to generate excitement and enthusiasm throughout its 23-year
      mission to assess worker and public health risks from radiation exposure
      resulting from nuclear weapons production activities in the former Soviet Union.
      The three goals of the Program are to: (1) clarify the relationship between
      health effects and chronic, low-to-medium dose radiation exposure; (2) estimate
      the cancer risks from exposure to gamma, neutron, and alpha radiation; and (3)
      provide information to the national and international organizations that
      determine radiation protection standards and practices. Research sponsored by
      DOE's Russian Health Studies Program is conducted under the authority of the
      Joint Coordinating Committee for Radiation Effects Research (JCCRER), a bi
      national committee representing Federal agencies in the United States and the
      Russian Federation. Signed in 1994, the JCCRER Agreement established the legal
      basis for the collaborative research between USA and Russian scientists to
      determine the risks associated with working at or living near Russian former
      nuclear weapons production sites. The products of the Program are peer-reviewed
      publications on cancer risk estimates from worker and community exposure to
      ionizing radiation following the production of nuclear weapons in Russia. The
      scientific return on investment has been substantial. Through 31 December 2015,
      JCCRER researchers have published 299 peer-reviewed publications. To date, the
      research has focused on the Mayak Production Association (Mayak) in Ozersk,
      Russia, which is the site of the first Soviet nuclear weapons production
      facility, and people in surrounding communities along the Techa River. There are
      five current projects in the Russian Health Studies Program: two radiation
      epidemiology studies; two historical dose reconstruction studies and a worker
      biorepository. National and international standard-setting organizations use
      cancer risk estimates computed from epidemiological and historical dose
      reconstruction studies to validate or revise radiation protection standards. An
      overview of the most important research results will be presented.

PMID- 27885078
TI  - The International Nuclear Workers Study (Inworks): A Collaborative
      Epidemiological Study to Improve Knowledge About Health Effects of Protracted Low
      Dose Exposure.
AB  - INWORKS is a multinational cohort study, gathering 308 297 workers in the nuclear
      industry in France, the United Kingdom and the United States of America, with
      detailed individual monitoring data for external exposure to ionising radiation.
      Over a mean duration of follow-up of 27 y, the number of observed deaths was 66
      632, including 17 957 deaths due to solid cancers, 1791 deaths due to
      haematological cancers and 27 848 deaths due to cardiovascular diseases. Mean
      individual cumulative external dose over the period 1945-2005 was 25 mSv.
      Analyses demonstrated a significant association between red bone marrow dose and
      the risk of leukaemia (excluding chronic lymphocytic leukaemia) and between colon
      dose and the risk of solid cancers. INWORKS assembled some of the strongest
      evidence to strengthen the scientific basis for the protection of adults from low
      dose, low-dose rate, exposures to ionising radiation.

PMID- 27885079
TI  - The Work of ICRP on the Ethical Foundations of the System of Radiological
      Protection.
AB  - The International Commission on Radiological Protection (ICRP) has established
      Task Group 94 (TG 94) to develop a publication on the ethical foundations of the
      system of radiological protection aiming to consolidate the basis of ICRP's
      recommendations, to improve the understanding of the system and to provide a
      basis for communication on radiation risk and its perception. Through the review
      of the publications of the Commission and the conduct of a series of workshops,
      TG 94 has identified the key components of the ethical theories and principles
      relevant to the system of radiological protection. The purpose of eliciting the
      ethical values underpinning the system of radiological protection is not only to
      clarify the rationale of the recommendations made by the Commission, but also to
      assist in discussions related to its practical implementation. The report nearing
      completion by TG 94 will present the key steps concerning the scientific, ethical
      and practical evolutions of the system of radiological protection since the first
      ICRP publication in 1928, describe the core ethical values underpinning the
      present system and address the key procedural aspects for its implementation.

PMID- 27885080
TI  - IMPORTANCE OF ENGAGING IN DIALOGUE WITH THE POPULATION AFTER A NUCLEAR ACCIDENT.
AB  - Human behaviour is primarily driven by perceptions and this is particularly
      important in the aftermath of a nuclear accident. One of the main lessons we can
      draw from the Chernobyl and Fukushima accidents is that once the acute phase of
      the accident is over, it is important to engage in dialogue with the affected
      population. Science-based government measures, imposed from above, give rise to
      much opposition. Examples of this are the aversion of having to live in a
      contaminated territory, the reluctance of consumers to buy even slightly
      contaminated food and the opposition of most evacuees to return to their old
      homes. The continuing controversy within the scientific community about low-dose
      risks, which results in conflicting messages to the population, is also not very
      helpful. A way to deal with these problems is by empowering the affected
      population by establishing a kind of formal consultation structure funded by the
      authorities but operated by the local community. This will give the population
      the feeling of having some control over the situation. Such a participatory
      approach is very demanding for the authorities, but is likely to change the state
      of mind of the affected people from victims to survivors.

PMID- 27885081
TI  - NUCLEAR NEW BUILD-INTEGRATING CULTURAL DIFFERENCES IN RADIATION PROTECTION.
AB  - Across the world, we are seeing a resurgence in Nuclear New Build. In the UK
      alone, plans are under way for the construction of 10 new reactors, using 4
      different reactor designs all of which are to be provided by foreign vendors, and
      operated by 3 newly formed licensees within the UK. As these new licensees embark
      on the task of establishing themselves and progressing the design and build of
      these reactors, there are challenges faced in integrating the Radiation
      Protection Requirements and Culture from the various Foreign Investors and
      Vendors into the UK 'Context'. The following paper identifies the origin of the
      Radiation Protection Requirements within the UK and foreign investor/vendor
      countries, in an attempt to integrate them into the UK licensing and approval
      process. Thus, allowing due credit to be taken for the regulatory regime of the
      foreign countries where these reactors originate.

PMID- 27885082
TI  - THE SIZE-SPECIFIC DOSE ESTIMATE (SSDE) FOR TRUNCATED COMPUTED TOMOGRAPHY IMAGES.
AB  - The purpose of this study is to investigate truncated axial computed tomography
      (CT) images in the clinical environment and to produce correction factors for
      abdomen, thoracic and head regions based on clinical data, in order to accurately
      predict the water-equivalent diameter (DW) and size-specific dose estimate
      (SSDE). We investigated axial images of 75 patients who underwent CT
      examinations. Truncated axial images were characterized by the truncation
      percentage (TP). Correction factors were calculated by using the value of DW for
      a certain TP (truncated image) divided by the value of DW for TP = 0% (the non
      truncated image). Most of the thorax images acquired for this study were
      truncated images (86.2%), in the abdomen region about half of the images were
      truncated (48.1%), and in the head region only a small portion were truncated
      (9.1%). In the thorax region the value of TP for the truncated images varied up
      to 50%, in the abdomen region it varied up to 35%, and in the head region it was
      smaller than 10%. We have shown how to accurately estimate DW and SSDE by
      applying a correction factor to the truncated images. The correction factors
      increase exponentially with increasing TP. The corrected DW and SSDE for the
      truncated images were significant in the thoracic region, but were not
      significant in the abdomen and head regions.

PMID- 27885083
TI  - Internal Dose Assessment of New 177Lu-Radiopharmaceuticals and Its Role in
      Radiation Protection of Patients.
AB  - Since 2006, CNEA has been conducting studies on the production, labeling, quality
      control and NIH mice biodistribution of several radiopharmaceuticals based on
      177Lu locally produced. In order to contribute to ensuring the radiation
      protection of patients, the Internal Dosimetry Laboratory of the ARN has been
      complementing the preclinical study performing a dose assessment. This assessment
      included: the activity biodistribution analysis in NIH mice, the estimation of
      the absorbed dose, the extrapolation of the results to humans, the identification
      of healthy organs with high risk and the estimation of the maximum activity that
      can be administered to a patient without exceeding the threshold of radiotoxicity
      in healthy organs. It can be observed that internal dosimetry assessment has an
      important role for ensuring radiation protection in patients, since treatment
      parameters can be optimized out of the estimation of the maximum activity to be
      administered to the patient.

PMID- 27885085
TI  - IMMUNOLOGICAL MONITORING OF THE PERSONNEL AT RADIATION HAZARDOUS FACILITIES.
AB  - The study of possible mechanisms resulting in changes in the immune system after
      exposure to ionizing radiation is an area that has not been thoroughly evaluated
      during recent years. This article presents an overview of immunological
      monitoring studies of personnel from the radiation-hazardous factories that took
      place over the past 20 years in Russia. The methodology of these studies is based
      on: (1) the preclinical evaluation of immune status of workers whose occupation
      involves potential exposure to ionizing radiation; (2) selecting at risk groups
      according to the nature of immune deficiency manifestation; and (3) studying the
      changes of immune status of employees with regard to the potential effects of
      radiation exposure. The principal aim of these studies is accumulation of new
      data on the impact of radiation exposure on the human immune system and search
      for the relationship between the clinical manifestations of immune disorders and
      laboratory parameters of immunity to improve the monitoring system of the health
      status of the professional workers involved in radiation-hazardous industrial
      environments and the population living close to these facilities.

PMID- 27885084
TI  - Analysis of Neutron Production in Passively Scattered Ion-Beam Therapy.
AB  - A new treatment facility for heavy ion therapy since 2010 was constructed. In the
      broad beam, a range shifter, ridge filter and multi leaf collimator (MLC) for the
      generation of the spread-out Bragg peak is used. In this case, secondary neutrons
      produced by the interactions of the ion field with beam-modifying devices (e.g.
      double-scattering system, beam shaping collimators and range compensators) are
      very important for patient safety. Therefore, these components must be carefully
      examined in the context of secondary neutron yield and associated secondary
      cancer risk. In this article, Monte Carlo simulation has been carried out with
      the FLUktuierende KAskade particle transport code, the fluence and distribution
      of neutron generation and the neutron dose equivalent from the broad beam
      components are compared using carbon and proton beams. As a result, it is
      confirmed that the yield of neutron production using a carbon beam from all
      components of the broad beam was higher than using a proton beam. The ambient
      dose by neutrons per heavy ion and proton ion from the MLC surface was 0.12-0.18
      and 0.0067-0.0087 pSv, respectively, which shows that heavy ions generate more
      neutrons than protons. However, ambient dose per treatment 2 Gy, which means
      physical dose during treatment by ion beam, is higher than carbon beam because
      proton therapy needs more beam flux to make 2-Gy prescription dose. Therefore,
      the neutron production from the MLC, which is closed to the patient, is a very
      important parameter for patient safety.

PMID- 27885086
TI  - Comparison of Primary Doses Obtained in Three 6 MV Photon Beams Using a Small
      Attenuator.
AB  - 17: It is a common technique in radiotherapy treatment planning systems to
      simplify the calculations by splitting the radiation beam into two components:
      namely the primary and scattered components. The contributions of the two
      components are evaluated separately and then summed to give the dose at the point
      of interest. Usually, the primary dose is obtained experimentally by
      extrapolating the ionization measured within the medium to zero-field size
      (Godden, Gamma radiation from cobalt 60 teletherapy units. Br. J. Radiol. Suppl.
      , 45(1983)). This approach offers the opportunity to obtain the primary component
      of dose without the need for an uncertain non-linear extrapolation. The primary
      dose can be obtained from two measurements of ionization in a large beam in a
      water phantom, as well as four measurements of ionization in a narrow beam
      geometry. The measurements were done over a range of different depths and thus
      the primary linear attenuation coefficient was also obtained. The calibrated
      output of a linear accelerator is usually 1.00 Gy per 100 monitor units (MU) at
      the depth of maximum dose ( d max ) in water for a 10 cm * 10 cm field. The
      values for the primary dose components at d max in a 10 cm * 10 cm field obtained
      in three different 6 MV beams using this method are D P ( d max , 10 cm * 10 cm)
      = 0.925-0.943 Gy/100 MU. The obtained values of the primary dose components
      compare well with measurements in the same beams extrapolated to zero-field size
      and also to literature. One can thus conclude that this method has the potential
      to provide an independent measurable verification of calculations of primary
      dose.

PMID- 27885087
TI  - LONG-TERM ELECTROMAGNETIC FIELD MEASUREMENT AND ASSESSMENT FOR A SHOPPING MALL.
AB  - As a result of the dense deployment of wireless devices and base stations,
      measuring and evaluating the electromagnetic (EM) exposure levels they emit have
      become important to human health especially if they exceed the limits defined in
      the standards. Base stations, Wi-Fi equipment and other electronic devices are
      used heavily, especially in densely crowded places like shopping centers. In this
      study, electric field strength (E) measurements were conducted at one of the
      largest shopping malls in Turkey. Broadband E measurements were performed using
      PMM 8053 EM field strength meter for 24 h a day for the duration of one week
      while frequency selective measurements were carried out with SRM-3006 EM field
      strength meter. It is concluded from the measurements that the mean measured
      total E in the band between 100 kHz and 3 GHz is 0.59 V/m while the maximum E is
      7.88 V/m, which are both below the limit determined by International Commission
      on Non-Ionizing Radiation Protection. Evolutions show that E can increase by up
      to 55% during the daytime. Analyses demonstrate that 71.3% of total E is caused
      by UMTS2100, 16.3% is produced by GSM900, 6.2% by LTE, 3.5% by Wi-Fi, and 2.7% is
      generated by devices that use the remaining frequency bands. Based on the
      detailed statistical analysis of long-term E measurement results, it can be
      concluded that the measured E levels are not in normal distribution and that they
      are statistically different with respect to days. Furthermore, distribution of E
      can be best modeled with the non-parametric approach.

PMID- 27885088
TI  - Survey of Effective Doses to Patients Undergoing Contrast-Based X-ray Fluoroscopy
      Procedures in Tanzania.
AB  - The aim of this study was to assess the radiation burden imparted to patients
      from contrast-based X-ray fluoroscopy procedures in Tanzania. The effective doses
      (EDs) to patients from five contrast-based fluoroscopy procedures were obtained
      from four hospitals. The ED was estimated using the knowledge of the patient
      characteristics, patient-related exposure parameters, measurements of air kerma
      area product and PCXCM software. The median EDs for the barium swallow (BS),
      barium meal (BM), barium enema (BE), hysterosalpingography (HSG) and retrograde
      urethrography (RUG) were 0.50, 1.43, 2.83, 0.65 and 0.59 mSv, respectively. The
      median ED per hospital for the BS and BM procedures varied by factors of up to
      9.9 and 4.2, respectively, while for the BE, HSG and RUG varied by factors of up
      to 2.3, 2.4 and 4.3, respectively. The overall differences between individual EDs
      across the four hospitals varied by factors of up to 53, 58.9 and 11.4 for the
      BS, BM and BE, respectively, while for the HSG and RUG differed by factors of up
      to 22 and 46.7, respectively. The mean EDs in this study were mostly lower than
      reported values from Spain, the UK, Ghana and Greece, while slightly higher than
      those reported from India. The observed wide variations of procedural protocols
      and patient doses within and across the hospitals; and the observed high patient
      doses in this study relative to those from the literature call for the need to
      standardize procedural protocols and optimize contrast-based fluoroscopy
      procedures.

PMID- 27885089
TI  - SLAYING THE DRAGON-THE STORY OF ONE FPSO, 20 VIETNAMESE OPERATORS AND 3 CONCRETE
      MIXERS.
AB  - End of life of a floating production, storage and offloading (FPSO) facility
      requires a lot of planning and management. One of the major challenges is the
      issue of decontamination and waste management. Waste disposal is a very sensitive
      subject and with agreements like the London Protocol and differences in
      legislation between countries, it has the potential to become a major stumbling
      block. Radiation safety is something not often on the mind of an FPSO operator.
      The planning and layout of such a vessel and its processing plant have usually
      not gone through any as low as reasonably achievable process during design.
      Planning the decontamination of such a vessel should start long before the actual
      decommissioning date. Performing regular vessel cleanouts and radiological
      profiling of the plant can be beneficial in the end. Finding a workable solution
      in getting naturally occurring radioactive material contaminated waste out of the
      vessels and tanks and effectively reducing the waste volumes for end of life
      clean-up is very important.

PMID- 27885090
TI  - THE IMPACT OF CIRCADIAN RHYTHMS ON MEDICAL IMAGING AND RADIOTHERAPY REGIMES FOR
      THE PAEDIATRIC PATIENT.
AB  - Daily rhythmic changes are found in cellular events in cell cycle, DNA repair,
      apoptosis and angiogenesis in both normal and tumour tissue, as well as in
      enzymatic activity and drug metabolism. In this paper, we hypothesize that
      circadian rhythms need to be considered in radiation protection and optimization
      in personalized medicine, especially for paediatric care. The sensitivity of the
      eye lens to ionizing radiation makes the case for limiting damage to the lens
      epithelium by planning medical radio-imaging procedures for the afternoon, rather
      than the morning. Equally, the tumour and normal tissue response to radiotherapy
      is also subject to diurnal variation enabling optimization of time of treatment.

PMID- 27885092
TI  - Nuclear and Radiological Preparedness: The Achievements of the European Research
      Project PREPARE.
AB  - The PREPARE project aimed closing gaps identified in nuclear and radiological
      preparedness in Europe following the first evaluation of the Fukushima disaster.
      With 46 partners from Europe and Japan, it collected the key players in the area
      of emergency management and rehabilitation preparedness. Starting from February
      2013, the project ended in January 2016. Among others, the project reviewed
      existing operational procedures for long-lasting releases, cross-border problems
      in radiation monitoring and food safety and further developed missing
      functionalities in decision support systems ranging from improved source term
      estimation and dispersion modelling to the inclusion of hydrological pathways for
      European water bodies. In addition, a so-called Analytical Platform has been
      developed to explore the scientific and operational means to improve information
      collection, information exchange and the evaluation of such types of disasters.
      The tools developed within the project will be partly integrated into the
      decision support systems ARGOS and JRODOS.

PMID- 27885091
TI  - INTERNATIONAL STANDARDS ON FOOD AND ENVIRONMENTAL RADIOACTIVITY MEASUREMENT FOR
      RADIOLOGICAL PROTECTION: STATUS AND PERSPECTIVES.
AB  - Radiological protection is a matter of concern for members of the public and thus
      national authorities are more likely to trust the quality of radioactivity data
      provided by accredited laboratories using common standards. Normative approach
      based on international standards aims to ensure the accuracy or validity of the
      test result through calibrations and measurements traceable to the International
      System of Units. This approach guarantees that radioactivity test results on the
      same types of samples are comparable over time and space as well as between
      different testing laboratories. Today, testing laboratories involved in
      radioactivity measurement have a set of more than 150 international standards to
      help them perform their work. Most of them are published by the International
      Standardization Organization (ISO) and the International Electrotechnical
      Commission (IEC). This paper reviews the most essential ISO standards that give
      guidance to testing laboratories at different stages from sampling planning to
      the transmission of the test report to their customers, summarizes recent
      activities and achievements and present the perspectives on new standards under
      development by the ISO Working Groups dealing with radioactivity measurement in
      connection with radiological protection.

PMID- 27885093
TI  - PROPOSALS FOR THE ESTABLISHMENT OF NATIONAL DIAGNOSTIC REFERENCE LEVELS FOR
      RADIOGRAPHY FOR ADULT PATIENTS BASED ON REGIONAL DOSE SURVEYS IN RUSSIAN
      FEDERATION.
AB  - In 2009-2014, dose surveys aimed to collect adult patient data and parameters of
      most common radiographic examinations were performed in six Russian regions.
      Typical patient doses were estimated for the selected examinations both in
      entrance surface dose and in effective dose. 75%-percentiles of typical patient
      effective dose distributions were proposed as preliminary regional diagnostic
      reference levels (DRLs) for radiography. Differences between the 75%-percentiles
      of regional typical patient dose distributions did not exceed 30-50% for the
      examinations with standardized clinical protocols (skull, chest and thoracic
      spine) and a factor of 1.5 for other examinations. Two different approaches for
      establishing national DRLs were evaluated: as a 75%-percentile of a pooled
      regional sample of patient typical doses (pooled method) and as a median of 75%
      percentiles of regional typical patient dose distributions (median method).
      Differences between pooled and median methods for effective dose did not exceed
      20%. It was proposed to establish Russian national DRLs in effective dose using a
      pooled method. In addition, the local authorities were granted an opportunity to
      establish regional DRLs if the local radiological practice and typical patient
      dose distributions are significantly different.

PMID- 27885094
TI  - NORWEGIAN-RUSSIAN COOPERATION IN NUCLEAR LEGACY REGULATION: CONTINUING EXPERIENCE
      AND LESSONS.
AB  - Safe management of nuclear legacies arising from past activities is a critical
      issue in maintaining confidence for the continuing and future use of radioactive
      materials. Effective and efficient regulatory supervision of nuclear legacy
      management is a critical part of that process. The Norwegian Radiation Protection
      Authority plays an active role in bilateral regulatory cooperation projects with
      sister authorities in the Russian Federation, as part of Norway's Plan of Action
      to improve radiation and nuclear safety. Based on this experience and by
      reference to specific legacy sites and facilities, this study provides an
      overview of the substantial progress made in remediation at the Site of Temporary
      Storage for spent fuel and radioactive waste at Andreeva Bay and presents
      radiation protection issues arising from the experience and lessons learned in
      this work. It is suggested that this experience can be useful in the further
      development of international recommendations, standards and guidance on
      remediation of nuclear legacies.

PMID- 27885095
TI  - REMEDIATION OF RADIUM LEGACIES FROM THE SWISS WATCH INDUSTRY.
AB  - Discovery of radioactive radium contaminations in a former landfill site in Biel
      was made in 2014. Following this, it was decided to search for and remediate
      sites that had possibly been contaminated with radium as a result of its use in
      the watchmaking industry between 1920 and 1960. This work describe the general
      approach to identify survey and remediate affected sites. The methods is based on
      the concept of existing exposure situations as developed by the International
      Commission on Radiological Protection, and is supported by an action plan for
      radium 2015-2019 approved by the Federal Council in 2015. The plan comprises four
      steps: the search for potentially contaminated sites, the measurement and
      assessment of each site, the remediation of those sites where the public would be
      exposed to an annual dose higher than 1 mSv, and actions to secure the landfill
      sites. The arrangements for each step are described in the present article. The
      measurement and remediation procedures imply intrusions into the privacy of the
      inhabitants. This requires the public authorities to actively inform the
      population and to develop an effective and transparent means of communication.
      The actions developed for this are also described.

PMID- 27885096
TI  - PROMOTING FLUOROSCOPIC PERSONAL RADIATION PROTECTION EQUIPMENT: UNFAMILIARITY,
      FACTS AND FEARS.
AB  - An incomplete understanding of risk can cause inappropriate fear. Personal
      protective equipment (PPE) offered for the prevention of brain cancer in
      interventional fluoroscopists (IR-PPE). Similar items are offered for cell-phone
      use (RF-PPE). Publications on fluoroscopy staff brain cancer and similar papers
      on cell-phone induced brain cancer were reviewed. An internet safety product
      search was performed, which resulted in many tens of thousands of hits. Vendor
      claims for either ionizing radiation or radio frequency products seldom addressed
      the magnitude of the risk. Individuals and institutions can buy a wide variety of
      safety goods. Any purchase of radioprotective equipment reduces the funds
      available to mitigate other safety risks. The estimated cost of averting an
      actuarial fatal brain cancer appears to be in the order of magnitude $10 000 000
      $100 000 000. Unwarranted radiation fears should not drive the radiation
      protection system to the point of decreasing overall safety.

PMID- 27885097
TI  - RESULTS OF RELID STUDY 2014-BUENOS AIRES, ARGENTINA RETROSPECTIVE EVALUATION OF
      LENS INJURIES AND DOSE.
AB  - High levels of scatter radiation in catheterization laboratories may lead to
      posterior subcapsular opacities in the lens of the staff. The international
      Retrospective Evaluation of Lens Injuries and Dose (RELID) was performed in
      Argentina for the first time in 2010 in the context of the congress of the Latin
      American Society of Interventional Cardiology (SOLACI) and recently, in 2014, was
      carried out for the second time (SOLACI-CACI 2014). The 2014 study included 115
      participants: interventional cardiologists, technicians and nurses. Posterior
      subcapsular lens changes typical of ionizing radiation exposure were found in
      91.5% of interventional cardiologists, in 77% of technicians and in 100% of
      nurses, according to the Merriam-Focht scale. This RELID study (Argentina 2014)
      has particular importance since it allowed the follow-up of 10 professionals
      evaluated in 2010. The results obtained in the study population highlight the
      importance of the availability and proper use of the elements of radiation
      protection, as well as staff training.

PMID- 27885098
TI  - Energy costs and performance of transfemoral amputees and non-amputees during
      walking and running: A pilot study.
AB  - BACKGROUND: Limited information is available concerning the effects of prosthetic
      foot components on energy costs and ambulatory performance for transfemoral
      amputees. OBJECTIVES: Compare energy costs (VO2; gait economy) and ambulatory
      performance (self-selected walking speeds, self-selected running speeds, peak
      running speeds) differences during walking and running for transfemoral amputees
      and matched, non-amputee runners. STUDY DESIGN: Repeated measures. METHODS:
      Transfemoral amputees were accommodated and tested with three prosthetic feet:
      conventional foot, solid-ankle cushioned heel (SACH); energy storing and return
      foot, Renegade; and running-specific energy storing and return foot, Nitro.
      RESULTS: During walking, VO2 was similar between transfemoral amputees but was
      increased compared to controls. Self-selected walking speeds were slower for SACH
      compared to Renegade and Nitro. For transfemoral amputees, gait economy was
      decreased and self-selected walking speeds were slower compared to controls.
      During fixed running speeds, transfemoral amputees ran using Nitro, and VO2 was
      greater compared to controls. Transfemoral amputees ran at self-selected running
      speeds using Renegade and Nitro. Self-selected running speeds were slower for
      Renegade compared to Nitro. For transfemoral amputees, gait economy was decreased
      and self-selected running speeds were slower compared to controls. VO2 peak was
      similar between transfemoral amputees and controls, but controls achieved greater
      peak running speeds and % grade. CONCLUSION: Energy costs were greater and
      ambulatory performance was lower for transfemoral amputees compared to matched,
      non-amputee controls for all prosthetic foot conditions. Clinical relevance Both
      types of energy storing and return feet may improve walking performance for
      transfemoral amputees by providing faster self-selected walking speeds. For
      transfemoral amputees interested in performing vigorous running (exercise and
      running competition), clinicians should recommend a running-specific energy
      storing and return foot.

PMID- 27885099
TI  - Rotationplasty in adult cancer patients: what is the rehab strategy and what
      results can be expected? A case study.
AB  - BACKGROUND AND AIM: Rotationplasty is an important and demanding challenge for
      physiotherapists. The aim of this paper is to describe the functional outcome
      achieved by a patient undergoing rotationplasty in adult age following
      osteosarcoma. Case description and Methods: The patient was followed throughout
      the rehabilitation course and the results achieved were recorded at 6, 9 and 12
      months after surgery. Findings and outcomes: The results progressively improved
      in terms of function, functional performance and quality of life. The MSTS and
      TESS scales showed an improvement respectively of 20 and 23 percentage points,
      reaching levels of 80% and 87%. The quality of life perceived by the patient
      increased in the three assessments, the mental health score at one-year follow-up
      is higher than that expected for the population. CONCLUSIONS: Rotationplasty,
      even in adult age, produces good results and in the treatment of tumours in
      adults this operation should be taken into consideration. Clinical relevance
      Rotationplasty in adult age following osteosarcoma combined with a rehabilitation
      program enabled a patient to reach a successful outcome in terms of functional
      performance and quality of life.

PMID- 27885101
TI  - Giant Cell Tumor of Talus: T-Construct Method of Bone Grafting.
AB  - : Giant cell tumor (GCT) or osteoclastoma is a benign, locally aggressive tumor
      with a tendency to recur. Giant cell tumors typically occur in the epiphysis of
      long bones, including the distal femur and proximal tibia. They are uncommonly
      found in the small bones of the foot or ankle, and involvement of talus is rare.
      The authors present a case of GCT of the talar body in a 21-year-old man, which
      was diagnosed radiologically by the presence of a well-defined osteolytic lesion
      involving more than half of the talar body with thinning of the cortices. An
      intralesional curettage and chemical cauterization with phenol was done using a
      medial approach following an osteotomy of the medial malleolus for adequate
      exposure. Intraoperative frozen section of curetted tissue was sent and was
      reported as benign GCT. The residual cavity was packed with autologous
      corticocancellous bone grafts fashioned in a T-construct like manner. A
      protective cast was applied for a period of 2 months and patient was subsequently
      gradually mobilized to full weightbearing status. At 2-year follow-up, there was
      no clinical or radiologically evident signs of recurrence. There was good
      consolidation of the bone graft in the talus with no signs of collapse of the
      weightbearing articular surface. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case
      Study.

PMID- 27885100
TI  - Temporal analysis of blood-brain barrier disruption and cerebrospinal fluid
      matrix metalloproteinases in rhesus monkeys subjected to transient ischemic
      stroke.
AB  - Blood-brain barrier (BBB) disruption plays an important role in
      pathophysiological progress of ischemic stroke. However, our knowledge of the
      dynamic change of BBB permeability and its mechanism remains limited. In the
      current study, we used a non-human primate (NHP) MCAO model and a serial CSF
      sampling method that allowed us to determine the dynamic change of BBB
      permeability by calculating the CSF/serum albumin ratio (AR). We showed that AR
      increased rapidly and significantly after ischemia, and the fold increase of AR
      is highly correlated with the infarction size during the subacute phase.
      Moreover, we determined the temporal change of MMP-1, MMP-2, MMP-3, MMP-9, MMP
      10, MMP-13, TIMP-1, and TIMP-2 in CSF and serum. Each MMP and TIMP showed
      different change patterns when comparing their values in CSF and serum. Based on
      the longitudinal dataset, we showed that the fold increase of MMP-9 in serum and
      CSF are both correlated to infarction size. Among the measured MMPs and TIMPs,
      only MMP-2, MMP-13, and TIMP-2 in CSF correlated with AR to some extent. Our data
      suggest there is no single MMP or TIMP fully responsible for BBB breakdown, which
      is regulated by a much more complicated signal network and further investigations
      of the mechanisms are needed.

PMID- 27885102
TI  - Technique Tip: Single-Incision Endoscopic Plantar Fasciotomy.
AB  - : Two-incision endoscopic plantar fasciotomy (EPF) is an accepted surgical
      technique in the treatment of recalcitrant plantar fasciitis. Single-incision
      plantar fasciotomy is a relatively new technique in the surgeons' armamentarium;
      however, it is not without pitfalls, specifically poor visualization. This
      article aims to help the foot and ankle surgeon make a smooth transition from 2
      incision EPF to single-incision EPF while maintaining optimum visualization.
      LEVELS OF EVIDENCE: Level V: Expert opinion.

PMID- 27885103
TI  - No support for lipid rescue in oral poisoning: A systematic review and analysis
      of 160 published cases.
AB  - Lipid rescue is used as treatment of various poisonings despite weak scientific
      evidence. Some experimental studies have indicated a positive effect, but others
      have not. Clinical studies are lacking, wherefore a systematic review of
      virtually all published human case reports is presented. The case reports were
      searched for in PubMed and Web of Science and examined by two experts according
      to an assessment form grading the probability for a causal connection between
      lipid rescue and improved symptoms. A total of 160 cases were finally included,
      of which 30 had no positive effect of lipid rescue. Among the 130 included cases
      with alleged positive effect, 94 were oral poisonings and 36 were cases with
      local anesthetic systemic toxicity (LAST). The experts' assessment resulted in a
      "certain" causal connection in three cases with LAST but not in oral poisoning.
      Moreover, the mean assessment score among the oral poisonings was significantly
      worse than the corresponding score in the cases with LAST. The average log p
      value of the main toxins among the oral poisonings was significantly lower than
      the corresponding p-value in the cases with LAST. Among the oral poisonings, 91%
      had received some other resuscitative treatment more or less simultaneously with
      lipid rescue. Considering the findings of this study and the increasingly
      reported adverse effects of lipid rescue, it's reasonable to strictly limit its
      use in clinical practice. We would not recommend it in oral poisonings.

PMID- 27885104
TI  - Could vitamin C and zinc chloride protect the germ cells against sodium arsenite?
AB  - Arsenic (As) is commonly associated with natural and human processes such as
      volcanic emissions, mining and herbicides production, being an important
      pollutant. Several studies have associated As intake with male fertility
      reduction, thus the aim of the present study was to evaluate whether vitamin C
      and/or zinc would counteract As side effects within the testicles. Adult male
      Wistar rats were divided into six experimental groups: control, sodium arsenite
      (5 mg/kg/day), vitamin C (100 mg/kg/day), zinc chloride (ZnCl2; 20 mg/kg/day),
      sodium arsenite + vitamin C and sodium arsenite + ZnCl2. Testicles and epididymis
      were harvested and either frozen or routinely processed to be embedded in glycol
      methacrylate resin. As reduced the seminiferous epithelium and tubules diameter
      due to germ cell loss. In addition, both the round spermatids population and the
      daily sperm production were reduced. However, ZnCl2 and vitamin C showed to be
      effective against such side effects, mainly regarding to sperm morphology. Long
      term As intake increased the proportions of abnormal sperm, whereas the
      concomitant intake of As with zinc or vitamin C enhanced the proportions of
      normal sperm, showing that such compounds could be used to protect this cell type
      against morphological defects.

PMID- 27885106
TI  - Publisher's Notice.

PMID- 27885105
TI  - Authors' Response to the Comments on "Pattern-Reversal Visual Evoked Potential
      Parameters and Migraine in the Teenage Population".

PMID- 27885107
TI  - A systematic review of clinical prediction scores for deep vein thrombosis.
AB  - Objective Diagnosis of deep vein thrombosis remains a challenging problem.
      Various clinical prediction rules have been developed in order to improve
      diagnosis and decision making in relation to deep vein thrombosis. The purpose of
      this review is to summarise the available clinical scores and describe their
      applicability and limitations. Methods A systematic search of PubMed, MEDLINE and
      EMBASE databases was conducted in accordance with Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidance using the keywords: clinical score,
      clinical prediction rule, risk assessment, clinical probability, pretest
      probability, diagnostic score and medical Subject Heading terms: 'Venous
      Thromboembolism/diagnosis' OR 'Venous Thrombosis/diagnosis'. Both development and
      validation studies were eligible for inclusion. Results The search strategy
      returned a total of 2036 articles, of which 102 articles met a priori criteria
      for inclusion. Eight different diagnostic scores were identified. The development
      of these scores differs in respect of the population included (hospital
      inpatients, hospital outpatients or primary care patients), the exclusion
      criteria, the inclusion of distal deep vein thrombosis and the use of D-dimer.
      The reliability and applicability of the scores in the context of specific
      subgroups (inpatients, cancer patients, elderly patients and those with recurrent
      deep vein thrombosis) remains controversial. Conclusion Detailed knowledge of the
      development of the various clinical prediction scores for deep vein thrombosis is
      essential in understanding the power, generalisability and limitations of these
      clinical tools.

PMID- 27885108
TI  - Increasing Our Advocacy Capacity Through HIV Community Mobilization: Perspectives
      From Emerging and Mid-Career Professionals.
AB  - In this commentary, six public health practitioners and researchers discuss how
      their participation in the El Paso HIV Community Mobilization effort has
      contributed to their professional development and increased their collective
      capacity to advocate for practice and policy improvements that contribute to
      health equity in general and within the context of HIV prevention. Like previous
      commentaries in this department that have highlighted the value of the Certified
      Health Education Specialist credential ( http://www.nchec.org/health-education
      credentialing ) and the importance of gaining experience in policy advocacy, this
      article is relevant for public health professionals in diverse work settings. The
      authors hope that their experience will encourage others to participate in
      community mobilization efforts, and they welcome communication and collaboration
      with anyone interested in learning more about the HIV Community Mobilization
      efforts discussed in this commentary.

PMID- 27885111
TI  - UK 'on track' to meet antibiotic use targets.

PMID- 27885114
TI  - Product recall alert.

PMID- 27885120
TI  - Challenges and opportunities of Brexit.
AB  - Some of the potential implications of Brexit for the veterinary profession were
      highlighted during the BVA Congress at the London Vet Show last week. A session
      run jointly by the BVA and the RCVS gave delegates the chance to hear how the two
      organisations are approaching the issue and discuss their own concerns. Kathryn
      Clark reports.

PMID- 27885123
TI  - Walk like a vet, think like an owner.
AB  - Owners consulting the internet before venturing into a veterinary practice is a
      real issue in today's technological age, but how often do vets step into the
      owner's shoes and try to understand why they do so? On the farm, what are the
      motivations of the farmer, and are these being listened to by the vet? These were
      just some of the questions raised in a session at the BVA Congress during the
      London Vet Show last week. Georgina Mills reports.

PMID- 27885124
TI  - Moving towards outcomes-based CPD.
AB  - ? Pilot trial of an outcomes-based model for CPD? Strategic plan for 2017 to
      2019? Changes to the statutory membership examinationThese were among matters
      discussed by the RCVS Council at its meeting on November 10. The RCVS President,
      Chris Tufnell, chaired the meeting, which was held at Belgravia House, London
      SW1P.

PMID- 27885125
TI  - Immature rumen fluke cause deaths of ewes.
AB  - Ewe deaths due to immature rumen flukeAmyloidosis in a Suffolk-cross
      lambHaemonchosis in Valais blacknose ewesDeaths and diarrhoea due to Salmonella
      Reading in 26-week-old giltsFeline dysautonomia in a kittenThese are among
      matters discussed in the disease surveillance report for August 2016 from SAC
      Consulting: Veterinary Services (SAC C VS).

PMID- 27885126
TI  - Why is L-2 hydroxyglutaric aciduria relevant for a general practitioner?

PMID- 27885128
TI  - Monitoring for re-emergence of Schmallenberg virus.

PMID- 27885131
TI  - Promoting the right image?

PMID- 27885133
TI  - Trial of gene therapy in diabetic dogs.

PMID- 27885141
TI  - Wild animals don't make appointments.
AB  - Bev Panto grew up with a keen interest in wildlife, as well as being an active
      member of a local conservation group and a 'young ornithologist'. Twenty years
      on, she is now a wildlife vet.

PMID- 27885142
TI  - Characterisation of ultraviolet-absorbing recalcitrant organics in landfill
      leachate for treatment process optimisation.
AB  - Organics in leachate from municipal solid waste landfills are notoriously
      difficult to treat by biological processes. These organics have high ultraviolet
      absorbance and can interfere with the ultraviolet disinfection process at the
      wastewater treatment plant that receives leachate if the leachate flow
      contribution is large enough. With more wastewater treatment plants switching to
      ultraviolet disinfection, landfills face increased pressure to treat leachate
      further. This study used size exclusion chromatography, fluorescence spectroscopy
      and ultraviolet/Vis spectrophotometry to characterise the bulk organic matter in
      raw landfill leachate and the biorecalcitrant organic matter in biologically
      treated leachate from the same site. The results indicate that biorecalcitrant
      organics have the polyphenolic absorbance peak at 280 nm, fluorescence peak at
      280 nm excitation and 315 nm emission, and molecular size range of 1000-7000 Da,
      all of which are consistent with lignin. The lignin-like nature of
      biorecalcitrant leachate organics is supported by the fact that 30%-50% of
      municipal solid waste consists of plant debris and paper products. These findings
      shed light on the nature of biorecalcitrant organics in leachate and will be
      useful for the design of leachate treatment processes and further research on
      leachate treatment methods.

PMID- 27885143
TI  - Intrapulmonary Percussive Ventilation as a Lung Recruitment Strategy in Brain
      Dead Organ Donors.
AB  - OBJECTIVE: To determine the strength of the evidence evaluating the effectiveness
      of intrapulmonary percussive ventilation (IPV) as a safe alternative or
      adjunctive therapy to traditional chest physiotherapy (CPT) among potential organ
      donors. DATA SOURCES: Literature search conducted from February 2015 to November
      2015 using PubMed, Cumulative Index of Nursing and Allied Health Literature,
      Scopus, and bibliographies of pertinent articles. Search Terms: Intrapulmonary
      percussive ventilation, chest physiotherapy, chest wall oscillation, organ
      donors, and ventilation. STUDY SELECTION: Articles in English from 1994 to
      present directly compared IPV to CPT or conventional (no) therapy. DATA
      EXTRACTION: Association of Critical-Care Nurses Levels of Evidence was used to
      determine the strength of evidence. Level B and level C articles were reviewed.
      DATA SYNTHESIS: No studies were found using IPV in the donor population. Results
      from studies using IPV in other populations indicated IPV had no adverse effects,
      improved sputum clearance and oxygenation, and reduced atelectasis and pneumonia
      in patients with artificial airways. CONCLUSION: Intrapulmonary percussive
      ventilation may be a safe and effective alternative or adjunctive to CPT therapy
      and improve the number of lungs available for transplantation. Clinical research
      is essential to determine the effectiveness of this therapy for lung recruitment
      in the donor population.

PMID- 27885144
TI  - Treatment of Multiple Myeloma in a Heart Transplant Recipient.
AB  - Malignancy following solid organ transplant remains a significant threat to the
      survival of cardiac transplant recipients. Plasma cell dyscrasias including
      multiple myeloma have been encountered in this population, and medication
      treatments traditionally used to treat these disorders demonstrate
      immunomodulatory effects that may have implications on the transplanted
      allograft. Lenalidomide is an immunomodulatory agent that has been used to treat
      plasma cell disorders, including light-chain amyloidosis (AL) and multiple
      myeloma, and represents such a class of medications in which the risks and
      benefits in the solid organ transplant population remain to be fully elucidated.
      This report highlights a clinical practice issue where the treatment of a
      patient's multiple myeloma with lenalidomide may have potentiated an episode of
      severe acute cellular rejection and further demonstrates the need for future
      investigation of the optimal treatment of plasma cell disorders including AL
      amyloidosis and multiple myeloma following solid organ transplantation.

PMID- 27885145
TI  - Trajectories of Postpartum Depression in Italian First-Time Fathers.
AB  - Paternal postpartum depression (PPD) has received little attention compared with
      maternal prenatal and postpartum depression, despite research reporting that
      paternal PPD concerns a substantial number of fathers. History of depression and
      antenatal depression have been identified as important PPD's risk factors,
      underlining the continuity of depressive symptoms during the transition to
      parenthood. However, only few studies have focused on the evolution of depressive
      symptoms with longitudinal research design. The present study aims at analyzing
      the longitudinal trajectories of depressive symptoms from the third trimester of
      pregnancy to 1 year after childbirth. One hundred and twenty-six first-time
      fathers completed the Edinburgh Postnatal Depression Scale at four time points (7
      8 months of pregnancy, 40 days, 5-6 months, and 12 months after childbirth). Data
      were analyzed throughout latent growth mixture modeling. Latent growth mixture
      modeling analysis indicated a three-class model as the optimal solution. The
      three-class solution included a trajectory of low, stable depressive symptoms
      across the four time points ( resilient, 52%); a trajectory of moderate,
      relatively stable depressive symptomatology ( distress, 37%); and a trajectory of
      emergent clinical depression following a pattern of high depressive symptoms (
      emergent depression, 11%). This study allowed to identify different subpopulation
      within the sample, distinguishing among mental well-being, emotional distress,
      and high-risk conditions when-1 year after childbirth-fathers report the highest
      scores to the Edinburgh Postnatal Depression Scale. These results underline the
      importance to analyze fathers' well-being over the time during the transition to
      fatherhood.

PMID- 27885146
TI  - Men's Educational Group Appointments in Rural Nicaragua.
AB  - Men's preventive health and wellness is largely neglected in rural Nicaragua,
      where a machismo culture prevents men from seeking health care. To address this
      issue, a men's educational group appointment model was initiated at a rural
      health post to increase awareness about hypertension, and to train community
      health leaders to measure blood pressure. Men's hypertension workshops were
      conducted with patient knowledge pretesting, didactic teaching, and posttesting.
      Pretesting and posttesting performances were recorded, blood pressures were
      screened, and community leaders were trained to perform sphygmomanometry. An
      increase in hypertension-related knowledge was observed after every workshop and
      community health leaders demonstrated proficiency in sphygmomanometry. In
      addition, several at-risk patients were identified and follow-up care arranged.
      Men's educational group appointments, shown to be effective in the United States
      in increasing patient knowledge and satisfaction, appear to function similarly in
      a resource-constrained environment and may be an effective mechanism for reaching
      underserved men in Nicaragua.

PMID- 27885147
TI  - "You Can't Just Walk Down the Street and Meet Someone": The Intersection of
      Social-Sexual Networking Technology, Stigma, and Health Among Gay and Bisexual
      Men in the Small City.
AB  - Social-sexual networking technologies have been reported to yield both
      psychosocial benefits and sexual risks for gay and bisexual men, yet little
      research has explored how technology interacts with the social-geographical
      environment to shape the health of gay and bisexual men in the relatively
      understudied environment of small cities. This article draws on 29 semistructured
      interviews examining the use of social-sexual networking technologies among
      racially diverse gay and bisexual men in two small cities. Questions probed
      participants' use of technology to meet sexual partners, engagement in the gay
      community, and the role of virtual and nonvirtual spaces in relation to health.
      Findings suggest that social networking technologies can help men navigate the
      challenges of small cities, including small and insular gay communities, lack of
      dedicated gay spaces, and sexual minority stigma. However, participants also
      describe declines in gay community visibility and cohesion, which they attribute
      to technology use. The article concludes by discussing the intersections of
      virtual and physical space in small cities as sites for the production of health
      and illness.

PMID- 27885148
TI  - Injury, Interiority, and Isolation in Men's Suicidality.
AB  - Men's high suicide rates have been linked to individual risk factors including
      history of being abused as a child, single marital status, and financial
      difficulties. While it has also been suggested that the normative influences of
      hegemonic masculinities are implicated in men's suicide, the gendered experiences
      of male suicidality are poorly understood. In the current photovoice study, 20
      men who previously had suicidal thoughts, plans, and/or attempts were interviewed
      as a means to better understanding the connections between masculinities and
      their experiences of suicidality. The study findings revealed injury,
      interiority, and isolation as interconnected themes characterizing men's
      suicidality. Injury comprised an array of childhood and/or cumulative traumas
      that fueled men's ruminating thoughts inhibiting recovery and limiting hopes for
      improved life quality. In attempting to blunt these traumas, many men described
      self-injuring through the overuse of alcohol and other drugs. The interiority
      theme revealed how suicidal thoughts can fuel hopelessness amid summonsing
      remedies from within. The challenges to self-manage, especially when experiencing
      muddled thinking and negative thought were evident, and led some participants to
      summons exterior resources to counter suicidality. Isolation included
      separateness from others, and was linked to abandonment issues and not having a
      job and/or partner. Self-isolating also featured as a protection strategy to
      avoid troubling others and/or reducing exposure to additional noxious stimuli.
      The study findings suggest multiple intervention points and strategies, the
      majority of which are premised on promoting men's social connectedness. The
      destigmatizing value of photovoice methods is also discussed.

PMID- 27885150
TI  - Doctor William Gunn (1804-1890): From the South Pacific Islands to Chatham Royal
      Dockyard.
AB  - Doctor William Gunn had a long and varied career in the Royal Navy. After
      spending time on anti-slavery patrols along the west coast of Africa, he was
      posted to the south Pacific. At Pitcairn Island, he treated the inhabitants
      during an influenza epidemic, proving himself to be a determined and dedicated
      practitioner. Subsequently, he was appointed head of the medical department at
      Chatham Royal Dockyard (1859-1865), an appointment that coincided with the final
      stages of the Royal Navy's transition from sail and wood to steam and iron. The
      impact of these changes on the health of dockworkers was quickly felt at Chatham,
      and Gunn found himself in charge during the building of the first iron warship in
      a royal dockyard. His story thus offers a window through which to observe a
      practitioner confronting the health issues and medical uncertainties thrown up by
      technological change in the Victorian era.

PMID- 27885151
TI  - Sushruta: Father of plastic surgery in Benares.
AB  - Sushruta has been regarded as one of the pioneers of surgery. He performed
      procedures with crude surgical instruments that paved the path for today's
      operations. However, his existence is shrouded in myth and mystery. Sushruta
      belonged to a rich heritage of learned scholars and practiced and taught surgery
      at Benares University around 600BC. His work is assembled into a monumental
      thesis, possibly the first text book on surgery, the 'Sushruta Samhita' where he
      describes surgical instruments, procedures, illnesses, medicinal plants and
      preparation, dissection and the study of human anatomy, embryology and fractures.
      Sushruta is perhaps best known for the nasal reconstruction flap which is still
      used in different versions. For all his contributions, he has been aptly titled
      'Father of Plastic Surgery'.

PMID- 27885149
TI  - Yoshitaka Komiya's visits to China and schistosomiasis investigation.
AB  - This article is about a Japanese parasitologist, Yoshitaka Komiya (1900-1976),
      who was invited to China for a schistosomiasis investigation in 1956. In 1955,
      Chairman Mao initiated a national campaign to eliminate schistosomiasis, which at
      that time was still common in southern China, and for this purpose, the People's
      Republic of China invited Yoshitaka Komiya to China. He published a report based
      on his observations during this visit. This article aims to explore the meaning
      of Komiya's visit to the People's Republic of China and his observations about
      the anti-schistosomiasis campaign.

PMID- 27885152
TI  - First use of ether anaesthesia under combat conditions.

PMID- 27885153
TI  - Karl Otto Landsteiner (1868-1943). Physician-biochemist-immunologist.
AB  - Karl Landsteiner applied the sciences of biochemistry, pathology, microbiology,
      and immunology in medical research to great success during the first half of the
      20th century. Although he is principally known for elucidating the major blood
      group antigens A and B and their isoantibodies for which he was awarded the Nobel
      Prize in Physiology or Medicine, Landsteiner made many other important medical
      discoveries. In that respect, he ascertained that paralytic poliomyelitis was due
      to a virus, the pancreas was damaged in cystic fibrosis, simple chemicals called
      haptens were able to combine with antibodies, and the Rh antigen that was later
      found to be the principal cause of hemolytic anemia of the newborn was found in
      most humans. Moreover, Landsteiner's book "The Specificity of Serological
      Reactions" was a precursor to the molecular revolution in immunology that
      occurred after Second World War. Finally, he was one of the leaders of the
      American Association of Immunology and of the Journal of Immunology.

PMID- 27885154
TI  - The Relationship Between Religiosity and Health-Promoting Behaviors in Pregnant
      Women.
AB  - Pender's health promotion model guided this descriptive/correlational study
      exploring the relationship between religiosity and health-promoting behaviors of
      pregnant women at Pregnancy Resource Centers (PRCs). A consecutive sample
      included women who knew they were pregnant at least 2 months, could read/write
      English, and visited PRCs in eastern Pennsylvania. Participants completed self
      report surveys that examined religiosity, demographics, pregnancy-related
      variables, services received at PRCs, and health-promoting behaviors. Women
      reported they "sometimes" or "often" engaged in health-promoting behaviors,
      Hispanic women reported fewer health-promoting behaviors than non-Hispanic women,
      and women who attended classes at the centers reported more frequent health
      promoting behaviors than those who did not attend classes. In separate multiple
      linear regressions, organized, non-organized, and intrinsic religiosity and
      satisfaction with surrender to God explained additional variance in health
      promoting behaviors above and beyond what Hispanic ethnicity and attending
      classes at the PRCs explained in pregnant women at PRCs.

PMID- 27885155
TI  - Job Crafting, Employee Well-being, and Quality of Care.
AB  - The main objective is to study the effects of job crafting activities of elder
      care and nursing home employees on their perceived well-being and quality of care
      in two European countries, Spain and Sweden. The Job Crafting, the General
      Health, and the Quality of Care questionnaires were administered to 530
      employees. Correlations and hierarchical regression analyses were performed.
      Results confirm the effects of job crafting on quality of care ( r = .291, p <
      .01; beta = .261, p < .01; Delta R2 = .065, p < .01) and employees' well-being (
      r = .201, p < .01; beta = .171, p < .01; Delta R2 = .028, p < .01). A positive
      linear relationship was found between job crafting and well-being in Spain and
      Sweden and with quality of care in Spain. On the contrary, in Sweden, the
      relationship between job crafting and well-being was not linear. Job crafting
      contributes significantly to employees' and residents' well-being. Management
      should promote job crafting to co-create meaningful and productive work. Cultural
      effects are proposed to explain the differences found.

PMID- 27885156
TI  - Namaste CareTM: A Person-Centered Care Approach for Alzheimer's and Advanced
      Dementia.
AB  - New methods of care are required to meet the needs of people with dementia and
      their caregivers. The Namaste CareTM program provides a person-centered approach
      through meaningful activities and loving touch. The purpose of this qualitative
      study was to explore the experiences of residents, staff, and family involved in
      the Namaste CareTM program at a long-term care facility in the United States. A
      descriptive approach was used to interview 14 staff members. The findings
      revealed six themes: peaceful sanctuary, relating their way, transforming
      experiences, connections and community, positive moments, and awakened to the
      possibilities. Results suggest that Namaste CareTM may be useful for individuals
      no longer able to participate in traditional long-term care setting activities.
      Further studies are indicated to confirm the impact on hospital readmissions,
      therapy enhancement, and medication use in relationship to Namaste CareTM program
      participation.

PMID- 27885157
TI  - Arab American Adolescents' Perceived Stress and Bullying Experiences: A
      Qualitative Study.
AB  - In 2012, 20% of high school students were bullied in the United States. Bullying
      is more prevalent among minority populations. Arab American adolescents receive
      little research attention and are described as the invisible population. This
      descriptive qualitative study was conducted with 10 Arab American adolescent
      bullying victims to describe their bullying experiences and related stress. In
      addition to being bullied because of health problems or social disadvantages,
      Arab American adolescents reported that they were bullied because of their
      ethnic/racial background and religious affiliation. Victims described high stress
      levels and anxiety which compromised their ability to function. They reported
      feeling sad, angry, overwhelmed, helpless, and hurt when they were bullied. They
      also lost control over their lives and self-confidence. Family and friends were
      sources of support but school administrators and teachers were not supportive.
      Implications for practice and future research were discussed.

PMID- 27885158
TI  - Psychosocial work environment in school and students' somatic health complaints:
      An analysis of buffering resources.
AB  - AIM: This study explores the association between the psychosocial work
      environment in school and students' somatic health complaints. With its point of
      departure from the Demand-Control-Support (DCS) model, the aim was to examine how
      aspects of decision control and social support can moderate stress-related health
      implications of high psychological demands. METHODS: Data come from two cross
      sectional waves of the Swedish version of Health Behaviour in School-aged
      Children (HBSC 2005/2006 and 2009/2010), which consists of a total of 9427 11-,
      13- and 15-year-old students. A two-level random intercept model was applied,
      with school class as the level 2 unit. RESULTS: Findings showed significant
      associations between school demands and somatic health complaints for all studied
      age groups, with a slight increase in strength with age. Decision control as well
      as social support from teachers, parents and peers consistently predicted a
      favorable association with health. An age pattern emerged in the analyses of
      stress-moderating resources. For 11 year olds parental support was the only
      resource that displayed a significant interaction with demands in relation to
      somatic health complaints, whereas for 13 year olds, decision control and support
      from teachers and parents all demonstrated moderating effects on student health.
      For 15 year olds, however, it was peer support that acted as a buffering resource
      in the studied relationship. CONCLUSIONS: The psychosocial work environment is an
      important predictor of students' health complaints. Overall, social support was a
      better stress-moderating resource than decision control, but some "buffers" were
      more important at certain ages than others.

PMID- 27885159
TI  - Friendship trust and psychological well-being from late adolescence to early
      adulthood: A structural equation modelling approach.
AB  - AIMS: This study explored the sex-specific associations between friendship trust
      and the psychological well-being of young Swedes from late adolescence to early
      adulthood. METHODS: A random sample of native Swedes born in 1990 was surveyed at
      age 19 years and again at age 23 years regarding their own well-being and their
      relationships with a maximum of five self-named peers. The response rate was
      31.3%, resulting in 782 cases to be analysed. We used sex-stratified structural
      equation models to explore the associations between trust and well-being.
      Psychological well-being was constructed as the latent variable in the
      measurement part. The structural part accounted for the autocorrelation of trust
      with respect to well-being over time and incorporated the cross-lagged effects
      between late adolescence and early adulthood. RESULTS: It was found that trust
      increased while well-being decreased for young men and remained stable for young
      women from 19 to 23 years of age. The young women reported lower well-being at
      both time points, whereas no sex difference was found for trust. Based on model
      fit comparisons, a simple model without forward or reward causation was accepted
      for young men, whereas reversed causation from well-being to trust was suggested
      for young women. Subsequent analysis based on these assumptions confirmed the
      reversed effect for young women. CONCLUSIONS: The findings suggest that young
      people do not benefit from trustful social relations to the same extent as adult
      populations. Young women who express impaired well-being run a greater risk of
      being members of networks characterized by low friendship trust over time.

PMID- 27885160
TI  - How unemployment and precarious employment affect the health of young people: A
      scoping study on social determinants.
AB  - BACKGROUND: The impact of unemployment and precarious employment on the health of
      young people is not well understood. However, according to social causation,
      higher socio-economic positions and thus better working conditions are beneficial
      to health in general. We tried to synthesize the results of studies that test
      this hypothesis in the case of young people. METHODS: We conducted a scoping
      study mapping all the academic articles published in the period 2006-2016 in
      Europe. The literature was searched in PubMed/Medline, Science Direct, Web of
      Science and Scopus. RESULTS: We identified 1770 studies, of which only 46 met the
      inclusion criteria. There are more studies that focus on the relationship between
      unemployment and health than between precarious employment and health (28 and 16,
      respectively). The vast majority of the studies (44) found support for the social
      causation hypothesis, the most common health outcomes being mental health
      disorders, health risk behaviour, poor quality of life and occupational injuries.
      The causal mechanisms behind this association relied mainly on the life-course
      perspective, the breadwinner model, and the lack of social and economic benefits
      provided by standard employment. CONCLUSIONS: There is evidence that young people
      are especially vulnerable to health problems when unemployed or working in
      precarious conditions. Active labour market and training programmes, inclusive
      social security measures, improved working conditions and targeted health
      programmes are important for addressing this vulnerability. Further research
      should strive to enhance the causal model by including a gender perspective,
      longitudinal data, more indicators on precariousness and third factor
      explanations.

PMID- 27885162
TI  - Contralesional Corticomotor Neurophysiology in Hemiparetic Children With
      Perinatal Stroke.
AB  - BACKGROUND: Perinatal stroke causes most hemiparetic cerebral palsy. Ipsilateral
      connections from nonlesioned hemisphere to affected hand are common. The
      nonlesioned primary motor cortex (M1) determines function and is a potential
      therapeutic target but its neurophysiology is poorly understood. OBJECTIVE: We
      aimed to characterize the neurophysiological properties of the nonlesioned M1 in
      children with perinatal stroke and their relationship to clinical function.
      METHODS: Fifty-two participants with hemiparetic cerebral palsy and magnetic
      resonance imaging-confirmed perinatal stroke and 40 controls aged 8 to 18 years
      completed the same transcranial magnetic stimulation (TMS) protocol. Single-pulse
      TMS to nonlesioned M1 determined rest and active motor thresholds (RMT/AMT),
      motor-evoked potential (MEP) latencies, and stimulus recruitment curves (SRC:
      100%-150% RMT). Paired-pulse TMS evaluated short-latency intracortical inhibition
      (SICI) and intracortical facilitation (ICF). Ipsilateral (IP) participants
      (ipsilateral MEP >=0.05 mV in >=5/20 trials) were compared with contralateral MEP
      only, nonipsilateral (NI) participants. Assisting Hand and Melbourne assessments
      quantified clinical function. RESULTS: Twenty-five IP were compared with 13 NI (n
      = 38, median age 12 years, 66% male). IP had lower motor function. SRC to
      unaffected hand were comparable between IP and NI while IP had smaller
      ipsilateral SRC. Ipsilateral MEP latencies were prolonged (23.5 +/- 1.8 vs 22.2
      +/- 1.5 ms contra, P < .001). Contralateral SICI was different between IP (-42%)
      and NI (-20%). Ipsilateral SICI was reduced (-20%). Contralateral ICF was
      comparable between groups (+43%) and ipsilaterally (+43%). Measures correlated
      between contralateral and ipsilateral sides. CONCLUSION: Neurophysiology of
      nonlesioned M1 and its relationship to motor function is measureable in children
      with perinatal stroke. Correlation of excitability and intracortical circuitry
      measures between contralateral and ipsilateral sides suggests common control
      mechanisms.

PMID- 27885161
TI  - A Rehabilitation-Internet-of-Things in the Home to Augment Motor Skills and
      Exercise Training.
AB  - Although motor learning theory has led to evidence-based practices, few trials
      have revealed the superiority of one theory-based therapy over another after
      stroke. Nor have improvements in skills been as clinically robust as one might
      hope. We review some possible explanations, then potential technology-enabled
      solutions. Over the Internet, the type, quantity, and quality of practice and
      exercise in the home and community can be monitored remotely and feedback
      provided to optimize training frequency, intensity, and progression at home. A
      theory-driven foundation of synergistic interventions for walking, reaching and
      grasping, strengthening, and fitness could be provided by a bundle of home-based
      Rehabilitation Internet-of-Things (RIoT) devices. A RIoT might include wearable,
      activity-recognition sensors and instrumented rehabilitation devices with radio
      transmission to a smartphone or tablet to continuously measure repetitions,
      speed, accuracy, forces, and temporal spatial features of movement. Using
      telerehabilitation resources, a therapist would interpret the data and provide
      behavioral training for self-management via goal setting and instruction to
      increase compliance and long-term carryover. On top of this user-friendly, safe,
      and conceptually sound foundation to support more opportunity for practice,
      experimental interventions could be tested or additions and replacements made,
      perhaps drawing from virtual reality and gaming programs or robots. RIoT devices
      continuously measure the actual amount of quality practice; improvements and
      plateaus over time in strength, fitness, and skills; and activity and
      participation in home and community settings. Investigators may gain more control
      over some of the confounders of their trials and patients will have access to
      inexpensive therapies.

PMID- 27885163
TI  - Clinically Important Difference of the Arm Motor Ability Test in Stroke
      Survivors.
AB  - BACKGROUND: The Arm Motor Ability Test (AMAT) is used to assess and quantify
      upper-extremity (UE) functional limitation in stroke and other conditions.
      However, the AMAT score change indicative of important and clinically meaningful
      change has not been determined. OBJECTIVE: To determine the clinically important
      difference (CID) for the AMAT for individuals with stroke exhibiting mild to
      moderate hemiparesis. METHODS: A total of 146 chronic stroke survivors exhibiting
      stable, mild to moderate UE hemiparesis were administered the AMAT before and
      after interventions targeting their affected UEs. Patients and treating
      therapists rated perceived amount of UE motor recovery for each participant on a
      global rating of change (GROC) scale evaluating several facets of UE movement
      (grasp, release, move the affected UE, perform 5 important functional tasks,
      overall UE function). Estimated CID of the Functional Ability Scale of the AMAT
      was calculated using the receiver operating characteristics curve with the GROC
      scale as the anchor. Distribution-based methods were also used to estimate the
      CID. RESULTS: Mean baseline, postintervention, and change in AMAT values for all
      participants were 3.0 (0.68), 3.3 (0.73), and 0.33 (0.43) respectively. The CID
      was estimated as an improvement of 0.32 to 0.42 when anchored by the therapist's
      perception of improvement and 0.29 to 0.40 when anchored by the patient's
      perception of improvement. The CID using distribution-based methods ranged from
      0.40 to 0.44. CONCLUSIONS: A change of 0.44 or greater on the AMAT indicates a
      clinically meaningful improvement in UE functional movements. Clinicians should
      use this value to determine goals and interpret change scores.

PMID- 27885164
TI  - Relation of statin use with non-melanoma skin cancer: Prospective results from
      the Women's Health Initiative.

PMID- 27885165
TI  - Neoadjuvant chemotherapy in breast cancers.
AB  - With advances in science and technology, there are more innovations in the
      approach to management of patients with breast cancer. Neoadjuvant chemotherapy
      that is designed to be used prior to surgical removal of a tumor has received
      significant attention. Currently, neoadjuvant chemotherapy is offered to patients
      with locally advanced breast cancer and also those breast cancer patients who may
      benefit from size reduction before conservation therapy. There is now sufficient
      evidence that if neoadjuvant chemotherapy leads to complete pathologic response,
      the patient will enjoy a better outcome. Therefore, assessment of the degree of
      response to neoadjuvant chemotherapy has a major impact on patient selection and
      the follow-up management of each patient and defines patient outcome.

PMID- 27885166
TI  - The role of interleukin-33 in chronic rhinosinusitis.
AB  - RATIONALE: Interleukin (IL)-33, a new member of the IL-1 family, is
      constitutively expressed in epithelial tissues and lymphoid organs and plays an
      important role in the pathogenesis of allergic disease. However, the role of IL
      33 in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear.
      OBJECTIVE: To investigate the role of IL-33 in the pathophysiology of CRSwNP.
      METHODS: We investigated IL-33 expression and its cellular origins in the nasal
      polyps (NPs) of human subjects by immunohistochemistry (IHC), quantitative
      reverse transcription PCR (qRT-PCR), and multiplex cytokine assays. Correlations
      between IL-33 expression and other inflammatory markers were also explored. To
      investigate the role of IL-33 in CRSwNP, anti-IL-33 antibody was used in a murine
      model of CRS. RESULTS: Uncinate process tissues from control (19), CRSsNP (61),
      CRSwNP (69) and NP tissues (71) were used in this study. Increased expression of
      IL-33 mRNA and protein in patients with CRSwNP compared with controls was
      observed. The concentration of IL-33 protein in CRSwNP was positively correlated
      with the number of neutrophils and the expression of several Th1 and Th17
      inflammatory markers, including interferon (IFN)-gamma, IL-1beta, tumour necrosis
      factor (TNF)-alpha, IL-17A, IL-22, and various markers for neutrophil
      recruitment. However, protein levels of IL-5 and quantity of eosinophils were
      inversely correlated with levels of IL-33. The expression of tissue inhibitor of
      metalloproteinase (TIMP)-1 was negatively correlated with IL-33 protein levels,
      while the expression of matrix metalloproteinase (MMP)-2 and MMP-9 was positively
      correlated with IL-33 protein levels. In animal studies, IL-33 expression was
      upregulated in the CRSwNP group compared with controls. Anti-IL-33 treatment
      reduced the thickness of oedematous mucosa, subepithelial collagen deposition,
      and infiltration of neutrophils, but infiltration of eosinophils was not reduced.
      This treatment also inhibited the expression of neutrophilic inflammatory
      cytokines, but not IL-4. In addition, the expression of intracellular adhesion
      molecule 1, vascular adhesion molecule 1 and CXCL-2 in the nasal mucosa was
      suppressed in mice treated with anti-IL-33 antibody. CONCLUSIONS: Our data
      suggest a role for IL-33 in the pathogenesis of CRSwNP via neutrophil
      recruitment. Therefore, anti-IL-33 may provide a new treatment strategy to target
      infiltrating neutrophils in CRSwNP.

PMID- 27885168
TI  - Educational and wealth inequalities in tobacco use among men and women in 54 low
      income and middle-income countries.
AB  - BACKGROUND: Socioeconomic differentials of tobacco smoking in high-income
      countries are well described. However, studies to support health policies and
      place monitoring systems to tackle socioeconomic inequalities in smoking and
      smokeless tobacco use common in low-and-middle-income countries (LMICs) are
      seldom reported. We aimed to describe, sex-wise, educational and wealth-related
      inequalities in tobacco use in LMICs. METHODS: We analysed Demographic and Health
      Survey data on tobacco use collected from large nationally representative samples
      of men and women in 54 LMICs. We estimated the weighted prevalence of any current
      tobacco use (including smokeless tobacco) in each country for 4 educational
      groups and 4 wealth groups. We calculated absolute and relative measures of
      inequality, that is, the slope index of inequality (SII) and relative index of
      inequality (RII), which take into account the distribution of prevalence across
      all education and wealth groups and account for population size. We also
      calculated the aggregate SII and RII for low-income (LIC), lower-middle-income
      (lMIC) and upper-middle-income (uMIC) countries as per World Bank classification.
      FINDINGS: Male tobacco use was highest in Bangladesh (70.3%) and lowest in Sao
      Tome (7.4%), whereas female tobacco use was highest in Madagascar (21%) and
      lowest in Tajikistan (0.22%). Among men, educational inequalities varied widely
      between countries, but aggregate RII and SII showed an inverse trend by country
      wealth groups. RII was 3.61 (95% CI 2.83 to 4.61) in LICs, 1.99 (95% CI 1.66 to
      2.38) in lMIC and 1.82 (95% CI 1.24 to 2.67) in uMIC. Wealth inequalities among
      men varied less between countries, but RII and SII showed an inverse pattern
      where RII was 2.43 (95% CI 2.05 to 2.88) in LICs, 1.84 (95% CI 1.54 to 2.21) in
      lMICs and 1.67 (95% CI 1.15 to 2.42) in uMICs. For educational inequalities among
      women, the RII varied much more than SII varied between the countries, and the
      aggregate RII was 14.49 (95% CI 8.87 to 23.68) in LICs, 3.05 (95% CI 1.44 to
      6.47) in lMIC and 1.58 (95% CI 0.33 to 7.56) in uMIC. Wealth inequalities among
      women showed a pattern similar to that of men: the RII was 5.88 (95% CI 3.91 to
      8.85) in LICs, 1.76 (95% CI 0.80 to 3.85) in lMIC and 0.39 (95% CI 0.09 to 1.64)
      in uMIC. In contrast to men, among women, the SII was pro-rich (higher smoking
      among the more advantaged) in 13 of the 52 countries (7 of 23 lMIC and 5 of 7
      uMIC). INTERPRETATION: Our results confirm that socioeconomic inequalities
      tobacco use exist in LMIC, varied widely between the countries and were much
      wider in the lowest income countries. These findings are important for better
      understanding and tackling of socioeconomic inequalities in health in LMIC.

PMID- 27885167
TI  - Mortality from respiratory diseases associated with opium use: a population-based
      cohort study.
AB  - BACKGROUND: Recent studies have suggested that opium use may increase mortality
      from cancer and cardiovascular diseases. However, no comprehensive study of opium
      use and mortality from respiratory diseases has been published. We aimed to study
      the association between opium use and mortality from respiratory disease using
      prospectively collected data. METHODS: We used data from the Golestan Cohort
      Study, a prospective cohort study in northeastern Iran, with detailed, validated
      data on opium use and several other exposures. A total of 50 045 adults were
      enrolled from 2004 to 2008, and followed annually until June 2015, with a follow
      up success rate of 99%. We used Cox proportional hazard regression models to
      evaluate the association between opium use and outcomes of interest. RESULTS:
      During the follow-up period, 331 deaths from respiratory disease were reported
      (85 due to respiratory malignancies and 246 due to non-malignant aetiologies).
      Opium use was associated with an increased risk of death from any respiratory
      disease (adjusted HR 95% CI 3.13 (2.42 to 4.04)). The association was dose
      dependent with a HR of 3.84 (2.61 to 5.67) for the highest quintile of cumulative
      opium use versus never use (Ptrend<0.001). The HRs (95% CI) for the associations
      between opium use and malignant and non-malignant causes of respiratory mortality
      were 1.96 (1.18 to 3.25) and 3.71 (2.76 to 4.96), respectively. CONCLUSIONS: Long
      term opium use is associated with increased mortality from both malignant and non
      malignant respiratory diseases.

PMID- 27885169
TI  - Children's exposure to secondhand smoke at home before and after smoke-free
      legislation in Taiwan.
AB  - INTRODUCTION: In January 2009, Taiwan broadened smoke-free legislation, requiring
      mass transportation systems, indoor public areas and indoor workplaces with 3 or
      more people, to become smoke-free. We investigated the secondhand smoke (SHS)
      exposure at home for children aged 3-11 years in Taiwan before and after the
      implantation of the legislation. METHODS: We studied 7911 children from the 2005,
      2009 and 2013 National Health Interview Surveys (cross-sectional, nationally
      representative household surveys). Logistic regression modelling estimated
      adjusted ORs (AOR) and 95% CIs for children's SHS exposure at home in 2009 and
      2013 (2005 as reference) for the overall sample and for each category of
      household socioeconomic status (SES) and household composition. RESULTS:
      Prevalence of children SHS exposure at home decreased from 51% (2005) to 32%
      (2009) and 28% (2013). Compared to 2005, children in 2009 and 2013 had lower
      likelihoods of SHS exposure at home with AOR of 0.45 (95% CI 0.41 to 0.51) and
      0.41 (95% CI 0.36 to 0.46), respectively. All children had reduced SHS exposure
      at home after the legislation, irrespective of household SES and compositions.
      Low household income, low parental education level, living with grandparents or
      living with other adults was individually associated with increased SHS exposure.
      DISCUSSION: The proportion of children exposed to SHS at home in Taiwan declined
      substantially from 2005 to 2009 after smoke-free legislation, and fell further by
      2013, irrespective of SES and household compositions. Still, inequality in SHS
      exposure at home by SES and household composition warrants future research.

PMID- 27885171
TI  - SAPFLUXNET: towards a global database of sap flow measurements.
AB  - Plant transpiration is the main evaporative flux from terrestrial ecosystems; it
      controls land surface energy balance, determines catchment hydrological responses
      and influences regional and global climate. Transpiration regulation by plants is
      a key (and still not completely understood) process that underlies vegetation
      drought responses and land evaporative fluxes under global change scenarios.
      Thermometric methods of sap flow measurement have now been widely used to
      quantify whole-plant and stand transpiration in forests, shrublands and orchards
      around the world. A large body of research has applied sap flow methods to
      analyse seasonal and diurnal patterns of transpiration and to quantify their
      responses to hydroclimatic variability, but syntheses of sap flow data at
      regional to global scales are extremely rare. Here we present the SAPFLUXNET
      initiative, aimed at building the first global database of plant-level sap flow
      measurements. A preliminary metadata survey launched in December 2015 showed an
      encouraging response by the sap flow community, with sap flow data sets from
      field studies representing >160 species and >120 globally distributed sites. The
      main goal of SAPFLUXNET is to analyse the ecological factors driving plant- and
      stand-level transpiration. SAPFLUXNET will open promising research avenues at an
      unprecedented global scope, namely: (i) exploring the spatio-temporal variability
      of plant transpiration and its relationship with plant and stand attributes, (ii)
      summarizing physiological regulation of transpiration by means of few water-use
      traits, usable for land surface models, (iii) improving our understanding of the
      coordination between gas exchange and plant-level traits (e.g., hydraulics) and
      (iv) analysing the ecological factors controlling stand transpiration and
      evapotranspiration partitioning. Finally, SAPFLUXNET can provide a benchmark to
      test models of physiological controls of transpiration, contributing to improve
      the accuracy of individual water stress responses, a key element to obtain robust
      predictions of vegetation responses to climate change.

PMID- 27885172
TI  - Isohydric species are not necessarily more carbon limited than anisohydric
      species during drought.
AB  - Isohydry (i.e., strong regulation of leaf water potential, Psil) is commonly
      associated with strict stomatal regulation of transpiration under drought, which
      in turn is believed to minimize hydraulic risk at the expense of reduced carbon
      assimilation. Hence, the iso/anisohydric classification has been widely used to
      assess drought resistance and mortality mechanisms across species, with isohydric
      species being hypothetically more prone to carbon starvation and anisohydric
      species more vulnerable to hydraulic failure. These hypotheses and their
      underlying assumptions, however, have rarely been tested under controlled,
      experimental conditions. Our objective is to assess the physiological mechanisms
      underlying drought resistance differences between two co-occurring Mediterranean
      forest species with contrasting drought responses: Phillyrea latifolia L.
      (anisohydric and more resistant to drought) and Quercus ilex L. (isohydric and
      less drought resistant). A total of 100 large saplings (50 per species) were
      subjected to repeated drought treatments for a period of 3 years, after which Q.
      ilex showed 18% mortality whereas no mortality was detected in P. latifolia.
      Relatively isohydric behavior was confirmed for Q. ilex, but higher vulnerability
      to cavitation in this species implied that estimated embolism levels were similar
      across species (12-52% in Q. ilex vs ~30% in P. latifolia). We also found similar
      seasonal patterns of stomatal conductance and assimilation between species. If
      anything, the anisohydric P. latifolia tended to show lower assimilation rates
      than Q. ilex under extreme drought. Similar growth rates and carbon reserves
      dynamics in both species also suggests that P. latifolia was as carbon
      constrained as Q. ilex. Increasing carbon reserves under extreme drought stress
      in both species, concurrent with Q. ilex mortality, suggests that mortality in
      our study was not triggered by carbon starvation. Our results warn against making
      direct connections between Psil regulation, stomatal behavior and the mechanisms
      of drought-induced mortality in plants.

PMID- 27885174
TI  - Plant responses to stress impacts: the C we do not see.

PMID- 27885176
TI  - [Short history on the birth of mechanobiology.]
AB  - In the last decade a new scientific discipline called "Mechanobiology" has
      emerged. It aims at elucidation of roles and mechanisms of mechanical forces in
      organisms as well as applications of the obtained fruits to human beings.
      Mechanobiology deals with a wide variety of objectives, including molecules,
      cells, tissues, organs and individuals, in which "Cell Mechanosesing" forms the
      core concept. Starting with a definition of cell mechanosensing, this short
      review gives an outline of the history of mechanobiology and perspectives on the
      mechanobiology in the near future.

PMID- 27885177
TI  - [Response to mechanical stimulus and cardiovascular homeostasis.]
AB  - Response to mechanical stimulus, including blood pressure regulation as a typical
      example, is essential for cardiovascular homeostasis. Traditionally, mechanism of
      blood pressure regulation can be divided into two categories:short term neural
      regulation via arterial baroreceptor reflex and long term humoral regulation via
      renin-angiotensin system. Recent studies have revealed that sensitivity of
      baroreceptor reflex is impaired in metabolic syndrome and aging. Moreover, it is
      suggested that the baroreceptor reflex is involved in long term blood pressure
      regulation. This review introduces the mechanism of mechanotransduction in the
      baroreceptor reflex.

PMID- 27885175
TI  - CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic
      Implications and Relationships with the Serrated Neoplasia Pathway.
AB  - The concept of a CpG island methylator phenotype (CIMP) was first introduced by
      Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent
      hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular
      carcinogenesis mechanism was consolidated by the identification of the serrated
      neoplasia pathway, in which CIMP participates in the initiation and progression
      of serrated adenomas. Distinct clinicopathological and molecular features of CIMP
      high (CIMP-H) CRCs have been characterized, including proximal colon location,
      older age of onset, female preponderance, and frequent associations of high-level
      microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or
      traditional serrated adenomas and thus tend to display the morphological
      characteristics of serrated adenomas, including epithelial serration, vesicular
      nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor
      prognosis and different responses of CRCs to adjuvant therapy depending on CIMP
      status indicate clinical implications. In this review, we present an overview of
      the literature documenting the relevant findings of CIMP-H CRCs and their
      relationships with the serrated neoplasia pathway.

PMID- 27885178
TI  - [Changes in cytosolic Ca2+dynamics associated with muscular dystrophy.]
AB  - Duchenne muscular dystrophy(DMD)is X-linked genetic disorder caused by a lack of
      the membrane-associated protein dystrophin. DMD is characterized by progressive
      muscle wasting secondary to repeated muscle damage and inadequate repair. The
      mechanisms underlying the functional impairments in dystrophic muscle have not
      yet been fully determined. However, several recent studies indicate that elevated
      intracellular Ca2+homeostasis is a cause or facilitator of the development of
      muscle weakness in muscular dystrophy. This review focuses on abnormalities of
      Ca2+homeostasis and the possibilities for treatment by counteracting the
      Ca2+dysregulation.

PMID- 27885179
TI  - [Bone homeostasis and Mechano biology.]
AB  - The weight-bearing exercises help to build bones and to maintain them strength.
      Bone is constantly renewed by the balanced action of osteoblastic bone formation
      and osteoclastic bone resorption both of which mainly occur at the bone surface.
      This restructuring process called "bone remodeling" is important not only for
      normal bone mass and strength, but also for mineral homeostasis. Bone remodeling
      is stringently regulated by communication between bone component cells such as
      osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often
      linked to various bone diseases. During bone remodeling, resorption by
      osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte
      location within the bone matrix and the cellular morphology, it is proposed that
      osteocytes potentially contribute to the regulation of bone remodeling in
      response to mechanical and endocrine stimuli.

PMID- 27885180
TI  - [Mechano-bioscience in heart disease and regenerative medicine.]
AB  - During cardiac development and maturation, the heart continuously receives
      hemodynamic stimuli, referred to mechanical stress. Mechanical stress governs
      both cardiac development and differentiation, and also plays an important role in
      the maintenance of cardiac homeostasis. Indeed, cardiac hypertrophic changes
      emerge as a result of adaptation to mechanical overload. However, it is difficult
      to measure the mechanical stress precisely. Therefore, the molecular mechanisms
      of hemodynamics-related diseases are minimally understood. The progress in
      mechanobioscience field has a potential to uncover the mechanisms of cardiac
      diseases, and is expected to result in drug discovery in the future.

PMID- 27885181
TI  - [Clinical manifestation and pathophyisological bases of sarcopenia.]
AB  - Age-related loss of skeletal muscle mass, strength and function is known as
      sarcopenia, and its diagnostic criteria is based on usual gait speed, grip
      strength, and skeletal muscle mass. Whereas underlying mechanisms of sarcopenia
      remains to be fully clarified, recent studies have suggested age-related changes
      in inflammatory status and humoral factors might contribute to the
      pathophysiology of sarcopenia and linkage between bone and muscle metabolism.

PMID- 27885182
TI  - [Cartilage metabolism and mechanobioscience.]
AB  - Joint cartilage is under exposure to repetitive mechanical stress. It is well
      known fact that the mechanical stress is a major cause of joint disorders such as
      osteoarthritis. However the molecular mechanisms of cartilage under mechanical
      stress remain unclear. In recent years, some notable mechanosensor or signal
      cascades relating to mechanotransduction had been identified, which might be
      promising targets for treatment of joint disorders.

PMID- 27885183
TI  - [Osteoporosis and Mechano-biosciences.]
AB  - Mechanical unloading due to long-term bedrest or microgravity during spaceflight
      causes a devastating influence on bone. Although bisphosphonates can prevent bone
      loss and hypercalciuria by mechanical unloading for up to 6 months, the influence
      of unloading for longer period of time is unknown. This is because mechanical
      loading is one of the most important stimuli for bone formation. Mechanical
      stress activates several intracellular signaling pathways. Among them, activation
      of stress-activated cation channel by fluid shear stress stimulates ERK-CREB
      signaling to enhance the expression of fos family transcription factors, which
      stimulates IL-11 expression in osteoblastic cells. IL-11 then enhances Wnt/beta
      catenin signaling, by suppressing the expression of Wnt/beta-catenin inhibitors,
      sclerostin and Dkks. Because Wnt/beta-catenin signal enhances responsiveness to
      mechanical stimuli, stimulation of Wnt/beta-catenin signaling may increase the
      effect of exercise in maintaining axial bone mass.

PMID- 27885184
TI  - [Mechanotransduction and mechanical control of gene expression.]
AB  - Cells change gene expression when they differentiate into different cell
      lineages. Cells also change their gene expression profiles to adapt to altering
      milieus. Even physical forces(for example, forces evoked by muscle contraction or
      exercise)change gene expression dramatically, although the molecular mechanisms
      of this physico-genetic link are largely unknown. Here, we summarize several
      works published recently, trying to highlight the physical force as an essential
      parameter of gene expression and maintenance of homeostasis.

PMID- 27885185
TI  - [Therapeutic strategy targeting membrane molecular meshanosensing.]
AB  - Our bodies possess systems to detect various mechanical stimuli, called
      mechanosensing. Mechanosensing taking place in the membrane can be classified
      into to ion channel-dependent one and ion channel-independent one. Ion channel
      dependent mechanosensing is a relatively rapid response, involving various
      mechanosen sensitive channels, including recently identified pannexin. In
      contrast, ion-channel-independent mechanosensing is a slow response, such as
      tissue remodeling, and the mechanism via integrin-actin interaction at the focal
      adhesion is well known.

PMID- 27885186
TI  - [p130Cas-Mediated Regulation of Mechanical Functions of Cells.]
AB  - It is 10 years since we reported Cas as a cell mechano-sensor that converts
      stretching force to a biochemical signal. While we have been looking into the
      mechanism of how Cas molecules are extended, it appears that the source of
      stretching force does not derive from actomyosin contraction, but originates from
      actin polymerization. Furthermore, we have found that phosphorylated Cas links
      actomyosin contraction to cell migration by tensin 1-mediated association with
      inwardly moving actin filaments. Collectively, Cas serves as a force sensor at
      the cell leading edges as well as a part of force transmission machinery, i.e.
      clutch, which drives the cell forward.

PMID- 27885187
TI  - [Role of Hippo-YAP/TAZ signaling pathway in mechanotransduction.]
AB  - Transcriptional coactivators YAP(yes associated protein)and TAZ(transcriptional
      coactivator with PDZ-binding motif)regulate gene expression through binding to
      transcription factors. Recently, some studies showed that YAP/TAZ activity
      responded to mechanical inputs such as stiffness of the extracellular matrix and
      the mechanical regulation of YAP/TAZ controlled cell proliferation or
      differentiation. Additionally, we revealed important roles of YAP in tissue
      formation and homeostasis through cellular tension and pressure. These reports
      indicate that YAP/TAZ are major factors in mechanotransduction connecting between
      the mechanical environment and cell responses.

PMID- 27885188
TI  - [Mechanisms of vascular dynamic homeostasis.]
AB  - Vascular endothelial cells(ECs)play a critical role in controlling a variety of
      vascular functions including maintenance of the vascular tone, blood coagulation
      and fibrinolysis, and selective permeability of proteins. It has recently become
      apparent that ECs respond to hemodynamic forces, namely, shear stress and
      stretch, by altering their morphology, functions and gene expression profile.
      These responses also play important roles in maintaining normal circulatory
      system functions and homeostasis, and their impairment leads to various vascular
      diseases, including hypertension, aneurysm and atherosclerosis. The mechanisms
      underlying the mechanotransduction, however, are not yet clearly understood. In
      this article, we review the literature on the EC responses to mechanical forces
      and their roles in the regulation of the circulatory system, while also
      discussing the mechanosensing mechanisms of ECs.

PMID- 27885189
TI  - [Tissue regenerative therapies based on regulatory mechanisms underlying bone and
      cartilage development.]
AB  - Regenerative medicine is an approach that maximizes the natural healing ability
      by modulating regeneration-inducing signals within appropriate cells in
      combination with scaffolds. Tissue repair processes and developmental processes
      largely share common molecular mechanisms. Being inspired by the mechanisms, a
      large number of studies have been carried out on development of efficient systems
      for bone and cartilage regeneration. It would be the next step in this field to
      achieve the stability of regenerated tissues by modulating signals and
      intracellular molecules that are involved in the maintenance and metabolism of
      the tissues.

PMID- 27885190
TI  - [Design of mechanobio-materials for cell manipulation and its application for
      stem cell manipulation.]
AB  - Recently, control of mechanobiologic response of cells has been a strong
      attractive issue for biomaterials sciences in relation to the requirements for
      optimization of cell-materials interactions. In this mini-review, we survey the
      typical parameters for designing the biomaterials to manipulate cell
      mechanobiology, i.e., mechanobio-materials. In addition, from the view of
      regenerative biomedical engineering, we introduce our recent approaches on the
      development of mechanobio-materials for stem cell manipulation that ensures the
      high-qualified stemness.

PMID- 27885191
TI  - [Modeling and simulation of trabecular pattern formation in a cancellous bone
      defect under mechanical forces.]
AB  - Understanding regeneration of the trabecular structure in cancellous bone defects
      is an important issue in bone tissue engineering and regenerative medicine.
      Biochemical and biomechanical viewpoints are indispensable for understanding the
      fundamental mechanism that underlies the regeneration of the trabecular
      structure. In vitro observations of the Turing pattern-like bone differentiation
      into osteoblasts from human mesenchymal stem cells suggest that mathematical
      modeling and simulation based on a reaction-diffusion system model would help us
      to understand the mechanism of trabecular pattern formation during cancellous
      bone regeneration. In this article, we propose a mathematical model of trabecular
      morphogenesis based on the reaction-diffusion system in 3D, which comprises
      activators and inhibitors of bone formation by combining with mechanical factors.
      Based on the proposed model, we conduct computational simulation of trabecular
      regeneration in a cancellous bone defect using a voxel-based finite element
      method for stress analysis and a finite difference method for reaction-diffusion
      analysis. The proposed model could express the regeneration of the three
      dimensional trabecular structure with mechanically adapted functions as a load
      bearing structure. Based on these results, the proposed model and simulation
      framework are expected to facilitate the analysis of regeneration of the
      cancellous bone;this will help us to examine bone regeneration that involve
      complex biological factors.

PMID- 27885192
TI  - Occurrence of two novel linear penta-amines, pyropentamine and homopyropentamine,
      in extremely thermophilic Thermus composti.

PMID- 27885193
TI  - Biodegradation of polycyclic aromatic hydrocarbons by a thermotolerant white rot
      fungus Trametes polyzona RYNF13.
AB  - The biodegradation of three polycyclic aromatic hydrocarbons (PAHs),
      phenanthrene, fluorene, and pyrene, by a newly isolated thermotolerant white rot
      fungal strain RYNF13 from Thailand, was investigated. The strain RYNF13 was
      identified as Trametes polyzona, based on an analysis of its internal transcribed
      spacer sequence. The strain RYNF13 was superior to most white rot fungi. The
      fungus showed excellent removal of PAHs at a high concentration of 100 mg.L-1.
      Complete degradation of phenanthrene in a mineral salt glucose medium culture was
      observed within 18 days of incubation at 30 degrees C, whereas 90% of fluorene
      and 52% of pyrene were degraded under the same conditions. At a high temperature
      of 42 degrees C, the strain RYNF13 was still able to grow, and degraded
      approximately 68% of phenanthrene, whereas 48% of fluorene and 30% of pyrene were
      degraded within 32 days. Thus, the strain RYNF13 is a potential fungus for PAH
      bioremediation, especially in a tropical environment where the temperature can be
      higher than 40 degrees C. The strain RYNF13 secreted three different ligninolytic
      enzymes, manganese peroxidase, laccase, and lignin peroxidase, during PAH
      biodegradation at 30 degrees C. When the incubation temperature was increased
      from 30 degrees C to 37 degrees C and 42 degrees C, only two ligninolytic
      enzymes, manganese peroxidase and laccase, were detectable during the
      biodegradation. Manganese peroxidase was the major enzyme produced by the fungus.
      In the culture containing phenanthrene, manganese peroxidase showed the highest
      enzymatic activity at 179 U.mL-1. T. polyzona RYNF13 was determined as a
      potential thermotolerant white rot fungus, and suitable for application in the
      treatment of PAH-containing contaminants.

PMID- 27885194
TI  - Isolation and characterization of a thermostable lipase from Bacillus
      thermoamylovorans NB501.
AB  - Two thermophilic bacterial strains, Bacillus thermoamylovorans NB501 and NB502,
      were isolated from a high-temperature aerobic fermentation reactor system that
      processes tofu refuse (okara) in the presence of used soybean oil. We cloned a
      lipase gene from strain NB501, which secretes a thermophilic lipase. The
      biochemical characteristics of the recombinant enzyme (Lip501r) were elucidated.
      Lip501r is monomeric in solution with an apparent molecular mass of 38 kDa on SDS
      PAGE. The optimal pH and apparent optimal temperature of Lip501r were 8 and 60
      degrees C, respectively. Supplementation of 5 mM Ca2+ enhanced the
      thermostability, and the enzyme retained 56% of its activity for 30 min at 50
      degrees C. Lip501r was active on a wide range of substrates with different
      lengths of p-nitrophenyl (pNP) esters, and showed a remarkably higher activity
      with pNP-myristate. The Km and Vmax values for pNP-butyrate in the presence of 5
      mM CaCl2 were 1.8 mM and 220 units/mg, respectively. The possible industrial use
      of the thermophilic lipase in modifying edible oil was explored by examining the
      degradation of soybean oil. A TLC analysis of the degraded products indicated
      that Lip501r is an 1,3-position specific lipase. A homology modeling study
      revealed that helix alpha6 in the lid domain of NB501 lipase was shorter than
      that of lipases from the Geobacillus group.

PMID- 27885195
TI  - Evaluation and Influence of Brachiocephalic Branch Re-entry in Patients With Type
      A Acute Aortic Dissection.
AB  - BACKGROUND: Stanford type A acute aortic dissection (A-AAD) extends to the
      brachiocephalic branches in some patients. After ascending aortic replacement, a
      remaining re-entry tear in the distal brachiocephalic branches may act as an
      entry and result in a patent false lumen in the aortic arch. However, the effect
      of brachiocephalic branch re-entry concomitant with A-AAD remains unknown.Methods
      and Results:Eighty-five patients with A-AAD who underwent ascending aortic
      replacement in which both preoperative and postoperative multiple-detector
      computed tomography (MDCT) scans could be evaluated were retrospectively studied.
      The presence of a patent false lumen in at least one of the brachiocephalic
      branches on preoperative MDCT was defined as brachiocephalic branch re-entry, and
      41 patients (48%) had this. Postoperatively, 47 of 85 (55%) patients had a patent
      false lumen in the aortic arch. False lumen remained patent after operation in 34
      out of the 41 (83%) patients with brachiocephalic branch re-entry, as compared to
      that in 13 of the 44 (30%) patients without such re-entry (P<0.001).
      Brachiocephalic branch re-entry was a significant risk factor for a late increase
      in the aortic arch diameter greater than 10 mm (P=0.047). CONCLUSIONS:
      Brachiocephalic branch re-entry in patients with A-AAD is related to a patent
      false lumen in the aortic arch early after ascending aortic replacement and is a
      risk factor for late aortic arch enlargement.

PMID- 27885196
TI  - Stent Recoil Manifesting as Early Stent Thrombosis After Ultimaster Thin-Strut,
      Cobalt-Chromium Sirolimus-Eluting Stent Implantation.

PMID- 27885198
TI  - The Difference between Ideal and Actual Fasting Duration in the Treatment of
      Patients with Aspiration Pneumonia: A Nationwide Survey of Clinicians in Japan.
AB  - In Japan, aspiration pneumonia is common among the elderly and patients are often
      treated by temporary discontinuation of meals. However, there are few published
      studies on the fasting duration for aspiration pneumonia treatment. Therefore, we
      conducted the present study to assess the opinions of clinicians regarding the
      fasting duration for the treatment of patients with aspiration pneumonia and the
      actual medical practice with regard to oral ingestion in hospitalized patients
      with aspiration pneumonia. We targeted hospitals with internal medicine and
      respiratory medicine departments across Japan. A questionnaire regarding the
      fasting duration for aspiration pneumonia treatment and oral ingestion in
      hospitalized patients with aspiration pneumonia was mailed to physicians treating
      patients with pneumonia at 2,490 hospitals. We received appropriate responses
      from 350 facilities (response rate, 14.1%). Most clinicians (78.3%) responded
      that it best to keep the fasting duration for treatment as short as possible and
      considered that fasting is absolutely unnecessary. Regarding oral ingestion in
      hospitalized patients, more than 25% of clinicians restricted oral intake for a
      certain number of days. The majority of these clinicians (53.3%) preferred
      prolonged fasting for 3 to 7 days. Although most physicians preferred the fasting
      duration to be as short as possible, there was a difference between the ideal and
      actual scenarios in reintroducing oral intake early in patients with aspiration
      pneumonia. Improving physicians' knowledge and experience will bridge the gap
      between the ideal situation and what currently occurs. Further studies should
      investigate the acceptable fasting duration for the treatment of aspiration
      pneumonia.

PMID- 27885197
TI  - A Thermostable Bilirubin-Oxidizing Enzyme from Activated Sludge Isolated by a
      Metagenomic Approach.
AB  - A gene coding for a multicopper oxidase (BopA) was identified through the
      screening of a metagenomic library constructed from wastewater treatment
      activated sludge. The recombinant BopA protein produced in Escherichia coli
      exhibited oxidation activity toward 2,2'-azino-bis-(3-ethylbenzothiazoline-6
      sulfonate) (ABTS) in the presence of copper, suggesting that BopA is laccase. A
      bioinformatic analysis of the bopA gene sequence indicated that it has a
      phylogenetically bacterial origin, possibly derived from a bacterium within the
      phylum Deinococcus-Thermus. Purified BopA exhibited maximum activity at pH 7.5
      with bilirubin as its substrate and was found to be active over a markedly broad
      pH range from 6 to 11. It also showed notable thermostability; its activity
      remained intact even after a heat treatment at 90 degrees C for 60 min. This
      enzyme is a thermostable-bilirubin oxidase that exhibits markedly higher
      thermostability than that previously reported for laccases.

PMID- 27885199
TI  - DRUG-INDUCED ANAPHYLAXIS.

PMID- 27885200
TI  - GUIDELINE OF TREATMENT OF ATOPIC DERMATITIS 2015.

PMID- 27885201
TI  - PATHOGENIC MEMORY Th2 CELLS AND ALLERGIC DISEASES.

PMID- 27885202
TI  - SUBLINGUAL IMMUNOTHERAPY FOR MITE ALLERGIC RHINITIS.

PMID- 27885203
TI  - EXAMINATION OF THE EFFECTIVENESS OF SLOW AND DEEP INHALATION OF FP/FM-pMDI FOR
      THE SMALL-AIRWAYS DYSFUNCTION OF ADULT-ONSET ASTHMA.
AB  - BACKGROUNDS: To date adult-onset asthmatic patients who lack a clear stridor and
      show prolonged coughs and chest discomfort caused by small-airways dysfunction
      have increased. We examined the small-airways function of these cases and the
      effectiveness of slow and deep inhalation of FP/FM-pMDI. METHODS: 62 adult-onset
      asthmatic patients who had prolonged coughs and chest discomfort with the middle
      or high dose of ICS/LABA combination agents under well technique (32 of BUD/FM
      DPI group and 30 of FP/SM-pMDI group) were included into this study. ICS/LABAs
      were switched to FP/FM-pMDI and slow and deep inhalation for 2-3 seconds was
      carried out thoroughly. The dose of FP/FM-pMDI was reduced depending on the
      improvement of symptoms. ACT score, respiratory function tests and respiratory
      resistance were measured after approximately six months from switching (stable
      condition after switching) and were compared with the values of the same period
      of the last year (stable condition under the previous ICS/LABA). RESULTS: After
      switching to FP/FM-pMDI, asthmatic symptoms and plural values of small-airways
      function were improved in 93.7% (30/32 cases) of BUD/FM-DPI group and in 86.6%
      (26/30 cases) of FP/SM-pMDI group. Moreover, mean daily inhalation doses were
      decreased from 5.0 to 4.3 in BUD/FM-DPI group and decreased from 5.7 to 3.7 in
      FP/SM-pMDI group. CONCLUSIONS: Slow and deep inhalation of FP/FM-pMDI is
      effective in many asthmatic patients who have prolonged small-airways
      dysfunction. A prospective, multi-centered contrastive study is warranted to
      confirm the effectiveness of this inhalational method.

PMID- 27885204
TI  - GENETIC INTERACTIONS BETWEEN ADRB2 AND PTGER4 ON RESPONSES TO SALMETEROL OR
      MONTELUKAST IN JAPANESE PATIENTS WITH MILD PERSISTENT ASTHMA.
AB  - BACKGROUND: Long-acting beta2-agonists (LABA) and leukotriene receptor
      antagonists (LTRA) are two principal agents that can be added to inhaled
      corticosteroids (ICS) for patients with asthma that is not adequately controlled
      by ICS alone. In our previous study, the Gly16Arg genotype of the beta2
      adrenergic receptor (ADRB2) gene did not influence the differential
      bronchodilator effect of salmeterol versus montelukast as an add-on therapy to
      ICS within 16 weeks of follow-up (the J-Blossom study). METHODS: We examined if
      genes encoding CYSLTR1, CYSLTR2, PTGER2 or PTGER4 could explain differential
      responses to salmeterol versus montelukast using the participants of the J
      Blossom study. This study included 76 patients with mild-to-moderate asthma. The
      difference in peak expiratory flow (PEF) (DeltaPEF, l/min) after 16 weeks of
      treatment with salmeterol (DeltaPEFsal) versus montelukast (DeltaPEFmon) was
      associated with the genotypes at each of 4 genes. In addition, multivariate
      analyses were used to identify a gene-gene interaction between ADRB2 gene and
      each of these 4 genes. RESULTS: Although none of 4 genes were associated with
      DeltaPEFsal-DeltaPEFmon in the univariate analyses, multivariate analysis showed
      that PTGER4 gene, interacting with ADRB2 Gly16Arg, was associated with
      DeltaPEFsal-DeltaPEFmon (p=0.0032). CONCLUSION: Our findings suggested that the
      interactions between two genetic loci at ADRB2 and PTGER4 is important in
      determining the differential response to salmeterol versus montelukast in
      patients with chronic adult asthma.

PMID- 27885205
TI  - CLINICAL EFFICACY OF SUBLINGUAL IMMUNOTHERAPY IN THE SECOND TREATED YEAR FOR 133
      PATIENTS WITH JAPANESE CEDAR POLLINOSIS IN 2016.
AB  - : It past 2 years in 2016 after the first purchase of the drug for sublingual
      immunotherapy (SLIT) for Japanese Cedar pollinosis (JCP). PURPOSE: The purpose of
      this study is to clear the clinical efficacy of SLIT in the second treated year
      by comparing with other therapies, such as subcutaneous immunotherapy (SCIT), or
      other pharmacotherapy. METHODS: We started SLIT at our clinic in October
      December, 2014. We compared the clinical efficacy in 2016, of 133 SLIT with 46
      SCIT, 351 primary pharmacotherapy that started therapies before pollen dispersal,
      221 pharmacotherapy that started therapies after pollen disposal, or 337 non
      treatment. The clinical efficacy was evaluated with symptom scores and combined
      symptom-medication scores (SMS), symptoms of nose and eye by visual analog scale
      (VAS), quality of life (QOL) scores by Japanese rhino-conjunctivitis QOL
      questionnaire (JRQLQ No1). RESULTS: Fourteen cases by unknown reasons and 3 cases
      by inevitable reasons were dropped out for 2 years. Both SCIT and SLIT showed
      good clinical efficacy without significant difference in every assessment. Both
      SCIT and SLIT were significantly better than other pharmacotherapy in most
      assessment. Patients, whose symptom scores of nose and eye were 0 or 1 point
      without any rescue drugs, accounted for 26.3% of total SLIT. CONCLUSION: SLIT in
      the second treated year showed good clinical efficacy in reducing symptoms and
      SMS of JCP, and in improving QOL. SLIT was significantly effective compaired with
      other pharmacotherapies.

PMID- 27885206
TI  - LONG-TERM FOLLOW-UP OF A CASE OF APPLE ALLERGY WITH SYSTEMIC SYMPTOMS THROUGH
      ORAL FOOD CHALLENGES.
AB  - To our knowledge, there are no previous reports of apple allergy with systemic
      symptoms for which repeated oral food challenges were performed over a long
      follow-up. The patient was an 8-year-old boy with hay fever. He visited our
      hospital because of nasal drop, itchy eyes, and dyspnea after lunch every two
      months for 2 years. Apple allergy was suspected through his medical interview and
      specific immunoglobulin (Ig) E levels, and he consequently underwent an oral food
      challenge test. Ninety minutes after ingestion of one whole apple, he experienced
      coughing, nasal drop, eyelid edema, and conjunctival injection. At age 14, he
      underwent a repeat oral food challenge test. This time, 55 minutes after
      ingestion, he experienced coughing, dyspnea, and wheezing and had to be treated
      by anti-histamine and steroid administration, as well as inhalation of a beta 2
      stimulant. At ages 8, 9, 11, 12, 13, and 14, the apple-specific IgE levels
      (Ua/ml) were <0.35, <0.35, 0.36, 0.54, 0.47, and 0.66, respectively. The alder
      specific IgE levels (Ua/ml) were <0.35, 0.49, 1.31, 2.14, 2.73, and 3.11; the Mal
      d 1-specific IgE levels (Ua/ml) were <0.10, 0.13, 0.25, 0.45, 0.88, and 1.1; and
      the Bet v 1-specific IgE levels (Ua/ml) were <0.10, 0.40, 1.0, 1.4, 2.4, and 2.8,
      respectively. These levels all gradually increased, whereas the specific IgE to
      Mal d 3 remained negative. The patient experienced systemic symptoms without
      mucosal symptoms, and these did not improve over time. In conclusion, we could
      follow this case of apple allergy with systemic symptoms through oral food
      challenge tests.

PMID- 27885208
TI  - ?

PMID- 27885207
TI  - ?

PMID- 27885210
TI  - ?

PMID- 27885209
TI  - ?

PMID- 27885211
TI  - Airflow equation for an exterior type plain circular hood.

PMID- 27885212
TI  - Let's try to determine the original reference value of highly stress on stress
      check program.

PMID- 27885213
TI  - A FRET Biosensor for ROCK Based on a Consensus Substrate Sequence Identified by
      KISS Technology.
AB  - Genetically-encoded biosensors based on Forster/fluorescence resonance energy
      transfer (FRET) are versatile tools for studying the spatio-temporal regulation
      of signaling molecules within not only the cells but also tissues. Perhaps the
      hardest task in the development of a FRET biosensor for protein kinases is to
      identify the kinase-specific substrate peptide to be used in the FRET biosensor.
      To solve this problem, we took advantage of kinase-interacting substrate
      screening (KISS) technology, which deduces a consensus substrate sequence for the
      protein kinase of interest. Here, we show that a consensus substrate sequence for
      ROCK identified by KISS yielded a FRET biosensor for ROCK, named Eevee-ROCK, with
      high sensitivity and specificity. By treating HeLa cells with inhibitors or
      siRNAs against ROCK, we show that a substantial part of the basal FRET signal of
      Eevee-ROCK was derived from the activities of ROCK1 and ROCK2. Eevee-ROCK readily
      detected ROCK activation by epidermal growth factor, lysophosphatidic acid, and
      serum. When cells stably-expressing Eevee-ROCK were time-lapse imaged for three
      days, ROCK activity was found to increase after the completion of cytokinesis,
      concomitant with the spreading of cells. Eevee-ROCK also revealed a gradual
      increase in ROCK activity during apoptosis. Thus, Eevee-ROCK, which was developed
      from a substrate sequence predicted by the KISS technology, will pave the way to
      a better understanding of the function of ROCK in a physiological context.

PMID- 27885214
TI  - Giant Leiomyoma Arising from the Mediastinal Pleura: A Case Report.
AB  - This report presents a rare case involving a patient with a giant leiomyoma
      originating from the mediastinal pleura. The patient underwent a medical
      examination, and chest radiography revealed a giant tumor. Computed tomography
      (CT) and magnetic resonance imaging (MRI) showed a well demarcated, heterogeneous
      mass which seemed to originate from the posterior mediastinum. Positron emission
      tomography (PET) showed the uptake of this tumor with a standardized uptake value
      of 4.9. We suspected that this tumor was a solitary fibrous tumor, and the
      patient underwent a surgical resection. Intraoperative exploration revealed a
      well-encapsulated tumor measuring 15 * 11 cm that appeared to originate from the
      mediastinal pleura. Immunohistochemical findings revealed a benign leiomyoma. We
      finally diagnosed the patient with a mediastinal leiomyoma. The present report
      describes CT, MRI, and PET findings of leiomyoma, and presents a review of
      relevant literature.

PMID- 27885215
TI  - Clinical Evaluation and Outcomes of Digital Chest Drainage after Lung Resection.
AB  - BACKGROUND: Analog chest drainage systems (ACS) are generally used to monitor
      postoperative alveolar air leakage (PAL) after lung resection. An electronic
      digital chest drainage system (DCS) has recently been developed that reportedly
      has several advantages over the traditional ACS. Here, we report a single
      institution's experience of PAL management with the DCS. We also sought to
      establish whether DCS had superior clinical benefits and outcomes compared with
      ACS. METHODS: We enrolled 112 consecutive patients who underwent lung resection
      and were subsequently managed with DCS. We compared PAL rate, duration of chest
      drainage, and the incidence of complications with a group of 121 consecutive
      patients previously managed with ACS after lung resection, using propensity score
      matching. RESULTS: Mean maximum and minimum PAL rates during DCS chest drainage
      were 48.9 ml/min (range: 2.0-868.6 ml/min) and 0.1 ml/min (0.0-1.2 ml/min),
      respectively. Mean PAL rate at DCS removal was 1.3 ml/min (0.0-10.0 ml/min).
      After propensity score matching, mean duration of chest drainage was
      significantly shorter with DCS than ACS (2.7 days, range: 1-9 days, compared with
      3.7 days, range: 1-21 days, respectively; P = 0.031). CONCLUSIONS: Managing PAL
      with DCS after pulmonary resection appears to reduce the duration of chest
      drainage.

PMID- 27885216
TI  - A novel heterozygous intronic mutation in POU1F1 is associated with combined
      pituitary hormone deficiency.
AB  - POU class 1 homeobox 1 (POU1F1) regulates pituitary cell-specific gene expression
      of somatotropes, lactotropes, and thyrotropes. In humans, two POU1F1 isoforms
      (long and short isoform), which are generated by the alternative use of the
      splice acceptor site for exon 2, have been identified. To date, more than 30
      POU1F1 mutations in patients with combined pituitary hormone deficiency (CPHD)
      have been described. All POU1F1 variants reported to date affect both the short
      and long isoforms of the POU1F1 protein; therefore, it is unclear at present
      whether a decrease in the function of only one of these two isoforms is
      sufficient for disease onset in humans. Here, we described a sibling case of CPHD
      carrying a heterozygous mutation in intron 1 of POU1F1. In vitro experiments
      showed that this mutation resulted in exon 2-skipping of only in the short
      isoform of POU1F1, while the long isoform remained intact. This result strongly
      suggests the possibility, for the first time, that isolated mutations in the
      short isoform of POU1F1 could be sufficient for induction of POU1F1-related CPHD.
      This finding improves our understanding of the molecular mechanisms, and
      developmental course associated with mutations in POU1F1.

PMID- 27885218
TI  - Unusual Case of Rupture of Right Sinus of Valsalva Aneurysm Into the Left
      Ventricle.

PMID- 27885217
TI  - Lymphocytic adrenal medullitis and lymphocytic thyroiditis in a laboratory beagle
      dog.
AB  - Lymphocytic adrenal medullitis characterized by inflammation and atrophy in the
      medulla of the bilateral adrenal glands was observed in an 18-month-old male
      laboratory beagle dog. It might be that the present lymphocytic adrenal
      medullitis is an autoimmune-mediated disease as the histological characteristics
      are consistent with an autoimmune pathogenesis. However, the actual cause remains
      unclear as the existence of serum autoantibodies against the adrenal medulla
      could not be confirmed. Although this dog also contracted lymphocytic thyroiditis
      along with serum thyroglobulin autoantibodies, indicating that the thyroiditis
      occurred with an autoimmune basis; the relation between the adrenal medullitis
      and thyroiditis is unknown.

PMID- 27885220
TI  - ?

PMID- 27885219
TI  - ?

PMID- 27885221
TI  - A new oral care gel to prevent aspiration during oral care.
AB  - AIM: Although oral care is important in the prevention of aspiration pneumonia,
      the different institutions and practitioners employ various oral care methods,
      some of which are associated with the risk of aspiration. We have developed a new
      gel with the physical properties needed for waterless oral care. In the present
      study, we evaluated and investigated the properties and effectiveness of this
      gel. METHODS: The physical properties of the trial gel and commercial
      moisturizing gels were compared using a VAS scale. The effects of plaque
      elimination were evaluated in healthy volunteers. Brushing was carried out by a
      dental hygienist using the gel and water. The number of throat suctions performed
      during brushing was also counted, and the difference was evaluated. RESULTS: In
      the evaluation of physical characteristics, trial Gel B showed a significantly
      higher rating than the other gels. In plaque elimination, the rate of decrease in
      a modified PCR was significantly greater with the gel trial. Suctioning was also
      performed significantly fewer times with the trial gel. CONCLUSIONS: Good results
      were obtained with the newly developed trial Gel B with regard to the physical
      properties and the sensory evaluations. Its effectiveness was also confirmed in
      plaque elimination and in the evaluated risk of aspiration. The use of Gel B may
      have the potential to decrease the risk of aspiration during oral care and reduce
      the occurrence of aspiration pneumonia.

PMID- 27885222
TI  - The development of a self-administered dementia checklist: the examination of
      concurrent validity and discriminant validity.
AB  - PURPOSE: The present study aims to develop a self-administered dementia checklist
      to enable community-residing older adults to realize their declining functions
      and start using necessary services. A previous study confirmed the factorial
      validity and internal reliability of the checklist. The present study examined
      its concurrent validity and discriminant validity. METHODS: The authors conducted
      a 3-step study (a self-administered survey including the checklist, interviews by
      nurses, and interviews by doctors and psychologists) of 7,682 community-residing
      individuals who were over 65 years of age. The authors calculated Spearman's
      correlation coefficients between the scores of the checklist and the results of a
      psychological test to examine the concurrent validity. They also compared the
      average total scores of the checklist between groups with different Clinical
      Dementia Rating (CDR) scores to examine discriminant validity and conducted a
      receiver operating characteristic analysis to examine the discriminative power
      for dementia. RESULTS: The authors analyzed the data of 131 respondents who
      completed all 3 steps. The checklist scores were significantly correlated with
      the respondents' Mini-Mental State Examination and Frontal Assessment Battery
      scores. The checklist also significantly discriminated the patients with dementia
      (CDR = 1+) from those without dementia (CDR = 0 or 0.5). The optimal cut-off
      point for the two groups was 17/18 (sensitivity, 72.0%; specificity, 69.2%;
      positive predictive value, 69.2%; negative predictive value, 72.0%). CONCLUSION:
      This study confirmed the concurrent validity and discriminant validity of the
      self-administered dementia checklist. However, due to its insufficient
      discriminative power as a screening tool for older people with declining
      cognitive functions, the checklist is only recommended as an educational and
      public awareness tool.

PMID- 27885223
TI  - A study on the mortality patterns of missing and deceased persons with dementia
      who died due to wandering.
AB  - AIM: To clarify the mortality patterns derived from differences in the causes of
      death and to subsequently promote search activity and prevent the death of
      missing persons. METHODS: The Ministry of Health, Labour and Welfare (MHLW)
      performed a mail survey using a self-administered questionnaire. The families of
      all 388 deceased dementia patients from among all of the missing persons reports
      involving dementia patients that were submitted to the police in 2013, and the
      10,322 missing persons with dementia (or suspected cases) were the subjects of
      this survey. The survey was conducted from January 5 to February 2 in 2015. We
      analyzed the data provided by the MHLW on 61 cases in which the cause of death
      was recorded; the factors that were related to the differences in the causes of
      death were examined using a chi-squared test (Fisher's direct method) and a
      residual analysis. Based on previous studies, we classified the causes of death
      into three categories: "drowning," "hypothermia," and "others (e.g., traumatic
      injury, disease progression)." RESULTS: When the cause of death was hypothermia,
      death often occurred between three to four days from the time that the deceased
      individual went missing. A significantly higher number of patients who died of
      other causes were found to have died on the day that they went missing. More than
      40% of the drowning cases occurred on the day that the deceased individual went
      missing. CONCLUSION: We identified 3 patterns of mortality: (1) death on the day
      that the deceased individual went missing due to traumatic injury, disease
      progression, drowning, and other causes; (2) death due to hypothermia within a
      few days after the deceased individual went missing; and (3) patterns other than
      (1) and (2).

PMID- 27885224
TI  - The attitude of Japanese individuals toward end-of-life care.
AB  - OBJECTIVE: To understand the attitude of Japanese individuals toward end-of-life
      care. SUBJECTS AND METHODS: The present study was conducted among the individuals
      who participated in a public seminar and completed a questionnaire related to end
      of-life care. We analyzed their responses. One hundred seventy-six participants
      (mean age: 64.7 years) answered the questionnaires, which asked whether they were
      familiar with the concept of a living will, who should decide their end-of-life
      care planning, what kind of nutritional support they would prefer to receive at
      the end-of-life, and what kind of medical treatments they were unwilling to
      receive. The answers were compared between the two age groups: those who were
      >=75 years of age and those who were <75 years of age. RESULTS: A total of 49%
      were aware of the concept of a living will and 8% had actually written a living
      will. The difference between the two groups was not statistically significant.
      Most of the respondents (76% of the respondents who were <75 years of age and 63%
      of the respondents who were >=75 years of age) thought that they should be able
      to decide on their end-of-life care planning themselves; however, more of the
      respondents who were >=75 years of age wanted to depend on their primary care
      physician for the decision. The proportion of respondents who wished to maintain
      only oral intake until the end of their life was 54%; there was no significant
      difference between the two groups. Among the subjects who were >=75 years of age,
      a smaller number of respondents indicated a medical treatment that they were
      unwilling to receive. CONCLUSION: In the present study, most of the late-elderly
      respondents indicated that they preferred to decide on their own end-of-life care
      planning by themselves, as was seen in younger respondents.

PMID- 27885225
TI  - The physical signs of impending dehydration among elderly people in nursing
      homes: The association with axillary skin temperature, humidity, intraoral
      moisture content, and salivary components.
AB  - PURPOSE: The aim of the present study was to examine the association between
      impending dehydration among elderly people in nursing homes and physical signs,
      including the axillary skin temperature, humidity, intraoral moisture content,
      and salivary components. METHODS: The study included 78 elderly individuals who
      required long-term care in a nursing home (11 men and 67 women; average age,
      86.6+/-7.3 years). The elderly subjects were classified in two groups according
      to their serum osmolality levels: those with levels between the upper limit
      reference value (292 mOsm/kg H2O) and the diagnostic reference value of
      dehydration (300 mOsm/kg H2O) were classified into the boundary zone group and
      those with levels of <292 mOsm/kg H2O were classified into the normal range
      group. The following parameters were measured: basic attributes (age, gender and
      level of care required), body mass index, diet, daily fluid intake per kilogram
      of body weight, physiological indicators (blood pressure, pulse rate, body
      temperature, axillary skin temperature, humidity, total body water, body water
      rate, internal liquid rate, external solution rate, blood components, intraoral
      water amount, and salivary components), and the indoor environment (room
      temperature and humidity). We then performed a statistical analysis to compare
      the boundary zone group with the normal range group. After adjusting for age and
      the daily fluid intake per kilogram of body weight (<25 ml/>=25 ml), we performed
      a logistic regression analysis (the boundary zone group was used as an
      independent variable) for variables that had significance levels of <0.05 (except
      for blood components). RESULTS: The univariate analysis revealed significant
      differences in the following parameters: the serum sodium, chloride, and
      creatinine levels; the blood sugar level; the urea nitrogen/creatinine ratio; the
      axillary skin temperature; and room humidity. Only the axillary skin temperature
      showed a significant association in the final model of the logistic regression
      analysis (odds ratio, 3.664; 95% confidence interval, 1.101-12.197; p = 0.034).
      CONCLUSION: As the axillary skin temperature increased by 1 degrees C, there was
      a 3.67-fold risk of being classified into the boundary zone group instead of the
      normal range group. Thus, the axillary skin temperature was associated with
      impending dehydration.

PMID- 27885226
TI  - Association between the nutritional status and the severity of sarcopenia among
      community-dwelling elderly Japanese people.
AB  - AIM: To investigate the association between nutritional evaluation indices (body
      mass index, albumin, and weight loss) and sarcopenia severity among community
      dwelling elderly people in Japan. METHODS: The subjects consisted of 758
      community-dwelling elderly people >=65 years of age, categorized into two groups
      by based on Operation of long life medical care system (medical care system for
      elderly in the latter stage of life), the cut-off value for age used was 75. The
      outcome measures were basic characteristics, anthropometric measures, physical
      function, and blood biochemistry (five assessments). The appendicular skeletal
      muscle mass was calculated via a bioelectrical impedance analysis. The subjects
      were categorized into three groups by the body mass index (BMI) [BMI 3 group].
      The cut-off value for albumin used was 3.8 g/dL [A1b 2 group]. Weight loss was
      assessed using item 11 on the Kihon check list: "Have you experienced more than 2
      3 kg weight loss over the past 6 months? Yes=1, No=0." [weight loss 2 group].
      Sarcopenia was defined based on the European Working Group on Sarcopenia in Older
      People definition, using the Asian Working Group for Sarcopenia cut-off values.
      All subjects were then categorized into four groups based on their sarcopenia
      status: non-sarcopenic (non-), pre-sarcopenic (pre-), sarcopenic (sarco-), or
      severely sarcopenic (severe-) [sarco4 group]. RESULTS: The prevalence of
      sarcopenia and severe sarcopenia in men was 5.6% (n=18) and 1.2% (n=4),
      respectively, and in women was 7.8% (n=34) and 1.6% (n=7), respectively. The
      analysis showed that, among the people (>75 years of age) with normal BMI (18.5
      25.0), 10.4%-15.6% were in the Sarco group. Further, among women over 75 years of
      age with BMI >25.0, 5.7% (n=2) were in the Sarco group. There was a significant
      association between weight loss and sarcopenia severity in older men. No
      significant association between albumin levels and sarcopenia severity was
      observed. 80.0% of weight-loss was presented in above BMI 18.5 kg/m2 and Alb 3.8
      g/dL. CONCLUSION: Sarcopenia and severe sarcopenia were prevalent among those
      with normal BMI, and particularly among obese women over 75 years of age. Weight
      loss was presented in above BMI 18.5 kg/m2 and Alb 3.8 g/dL. Our findings
      indicate that the nutritional evaluation indices, including BMI, albumin, and
      weight loss, were insufficient in screening for malnutrition and sarcopenia among
      the elderly.

PMID- 27885227
TI  - The experience of dissolving polypharmacy by reducing the prescription of anti
      ulcer drugs in residents of a special geriatric nursing home.
AB  - AIM: As part of a broader study on polypharmacy among elderly nursing home
      residents, we examined the impact of reducing or discontinuing the prescription
      of proton pump inhibitors and other anti-ulcer drugs. METHODS: We employed a
      strategy of reducing and discontinuing the prescription of drugs to 160 elderly
      residents of the Hiroshima Atomic Bomb survivors nursing home, Kandayama
      Yasuragien. The residents had entered the home between April 2012 and November
      2015. As part of this study into anti-ulcer drugs, we also measured the
      concentrations of Helicobacter pylori antigen in stool specimens, and the serum
      concentrations of H pylori antibodies and pepsinogen I and II. RESULTS: The
      proportions of residents who were taking more than six drugs on April 2012,
      August 2014 and November 2015 were 55.2%, 49.0% and 43.0%, respectively. At the
      same times, the proportions of residents who were taking anti-ulcer drugs were
      50.0%, 49.0% and 6.0%, respectively. The presence of H pylori antigen and
      antibodies, and serum pepsinogen concentrations, did not influence the decisions
      to continue or discontinue anti-ulcer drugs. CONCLUSIONS: We have already
      reported that reduction of diuretics reduces the incidence of falls and fall
      related fractures in our residents, and have demonstrated the benefits of
      discontinuing folic acid and drugs that are given to control hyperkalemia. In the
      present study, we found that many anti-ulcer drugs were also of low necessity to
      elderly care home residents. It is essential to examine the clinical benefits of
      addressing polypharmacy in elderly individuals. In the future, we intend to focus
      on reducing hypnotics, laxatives and other drugs.

PMID- 27885228
TI  - Factors associated with the prognosis of elderly patients with advanced dementia
      who receive palliative care from geriatric health services facilities.
AB  - AIM: The aim of the present study is to identify the factors associated with the
      prognosis of advanced dementia patients who are newly admitted to a geriatric
      health services facility. METHODS: This retrospective cohort study used data that
      were obtained on admission in the care-assessment of long-term care facility
      patients. The 177 participants with advanced dementia were admitted to our
      facility between 2006 and 2013. The association between the factors in the care
      assessment and the three-month-mortality rates were examined throughout the year.
      RESULTS: At each of the 3-month time points, the mortarity rates of the patients
      who had total dependence on oral eating or hypoalbuminemia (<3.5 g/dl by BCG
      method) were significantly higher in comparison to the patients who had neither
      of these factors. The mortality rates in the patients with a past history of
      pneumonia (within 3 months) were significantly associated with both factors. At
      each time point, the three-month-mortality rates showed a significant decrease in
      the following patients groups (in order): patients with both total dependence on
      oral eating and hypoalbuminemia, patients with dependence on oral eating or
      hypoalbuminemia, patients without these two factors. CONCLUSION: Our results
      indicate that the factors in the care-assessment. That were associated with the
      prognosis of patients with advanced dementia on admission may be total dependence
      on oral eating and hypoalbuminemia. Evaluating the combination of these two
      factors can be a simple and useful measure to identify advanced dementia patients
      with a high risk of death who receive palliative care in a geriatric health
      services facility.

PMID- 27885230
TI  - The implantation of a loop recorder to detect the cause of pre-syncope in an 85
      year-old man.
AB  - The patient was an-85-year-old man with hypertension and hyperlipidemia. The
      patient had a history of faintness on standing. He visited our hospital after
      experiencing chest oppression and pre-syncope in 2015. Brain magnetic resonance
      imaging and echocardiography did not detect any structural brain or heart
      disease. Ischemic heart disease was suspected based on the myocardial
      scintigraphy findings, but coronary angiography revealed no unusual findings.
      Holter electrocardiography did not reveal the reason for his symptoms. Because he
      had experienced 2-second sinus arrest rather than faintness or pre-syncope during
      the Holter monitoring (not an indication for the implantation of a pacemaker), we
      implanted a loop recorder to detect the cause of pre-syncope.The loop recorder
      required that he or his family to manually send the telemetry monitoring data,
      but he and his wife did not understand how to do it. After the loop recorder
      failed to reveal the cause of his symptoms, he was hospitalized for its
      extraction. When we manually checked the loop recorder data on the day of
      hospitalization, sinus arrest of >3 seconds was detected 271 times; the maximum
      sinus arrest was 4 seconds. Sinus arrest was confirmed to be cause of his
      symptoms. His symptoms completely disappeared after the implantation of a
      permanent pacemaker.Although faintness is not rare in elderly people, it can be
      difficult to diagnose. An implantable loop recorder was useful for diagnosing pre
      syncope; however, in the present case, it was difficult for the elderly patient
      and his wife to perform telemetry monitoring.

PMID- 27885229
TI  - The effects of the employment of physical therapists and occupational therapists
      on the gait function of adult day service users after 1 year.
AB  - OBJECTIVE: The present study aimed to investigate the effects of the presence or
      absence of physical therapists (PTs) and occupational therapists (OTs) in an
      adult day service on the users' gait function, and to generalize the format of an
      effective service aimed at the preventing the exacerbation of the gait function
      and at promoting self-reliance in activities and participation. METHODS: The
      study population included 830 elderly day service users (mean age, 83.7+/-6.8
      years; male, n=252; female, n=578) in Japan. Their normal gait speed was measured
      at the baseline and at 1 year. The sex, age, level of nursing care, and number of
      adult day service users were assessed at the baseline. The subjects were divided
      into 2 groups: (1) those who used services that employed PTs or OTs (the PTOT
      group) and (2) those who used services that did not employ PTs or OTs (the
      control group). We performed a univariate analysis to confirm the absence of
      differences between the groups in terms of all their baseline variables. Next, we
      performed a repeated measures analysis of variance using the presence or absence
      of PT or OT and time as factors. We subsequently performed a univariate analysis
      to examine the difference in the gait speed of the groups, as well as the
      differences in the gait speed between the groups at the baseline and at 1 year.
      RESULTS: Although the repeated measures analysis of variance did not show that
      time had a significant effect on the gait speed, it showed the significant
      effects of the presence or absence of PTs or OTs as well as the interaction
      between time and group. Intragroup comparisons showed a significant difference
      between the gait speed at baseline and that at 1 year in the PTOT group. However,
      there was also a significant difference in the baseline and 1-year gait speeds of
      the control group. The intergroup comparisons did not show a significant
      difference in the gait speed at baseline, but did show a significant difference
      in the gait speed at 1 year. CONCLUSION: The employment of PTs and OTs in adult
      day service controlled the exacerbation of the gait function. The gait speed in
      elderly individuals who require long-term care is associated with the activities
      of daily living and mortality rates; thus, the results of the present study
      indicate the need for the employment of rehabilitation specialists in adult day
      services.

PMID- 27885232
TI  - ?

PMID- 27885233
TI  - ?

PMID- 27885231
TI  - Two elderly patients with difficult-to-treat acquired hemophilia A.
AB  - We herein report the cases of two elderly patients with acquired hemophilia A
      (AHA) for whom treatment was difficult.An 89-year-old woman (Case 1) was admitted
      to our department with subcutaneous hemorrhage and melena. Her activated partial
      thromboplastin time (APTT), factor VIII activity, and factor VIII inhibitor level
      were 127.7 seconds, 1.0%, and 48 BU/mL, respectively, which was suggestive of
      AHA. The administration of prednisolone (PSL 0.5 mg/kg) was initiated. After 3
      weeks, PSL was combined with cyclophosphamide (CPA 50 mg). Two months after the
      start of treatment, her factor VIII inhibitor level decreased to 3.4 BU/mL.
      However, hemorrhagic signs were repeatedly observed during the discontinuation of
      recombinant activated factor VII (rFVIIa) preparation; bleeding control became
      insufficient, and pneumonia developed, thus leading to a fatal outcome.An 81-year
      old woman (Case 2) was admitted to our department with subcutaneous hemorrhage,
      anemia (Hb: 9.2 g/dL), and a prolonged APTT (78.7 seconds). Her factor VIII
      activity was reduced to 0.9%, and her factor VIII inhibitor level was markedly
      increased to 1,364.9 BU/mL, suggesting AHA. Treatment with PSL (0.5 mg/kg) was
      initiated. After one month, it was combined with CPA (50 mg); however, her
      hemorrhagic signs were protracted, and her Hb level decreased to 8.0 g/dL.
      Subsequently, pneumonia occurred. However, weekly rituximab therapy (375 mg/m2)
      for 4 weeks decreased her factor VIII inhibitor level, leading to the
      disappearance of the inhibitor at 1 year and 5 months. During this period, there
      were no episodes requiring the administration of bypassing agents, such as
      rFVIIa.

PMID- 27885234
TI  - ?

PMID- 27885235
TI  - ?

PMID- 27885236
TI  - Proceedings of Regional Meeting of the Japan Geriatrics Society.

PMID- 27885241
TI  - Effects of coke oven emissions and benzo[a]pyrene on blood pressure and
      electrocardiogram in coke oven workers.
AB  - OBJECTIVE: To evaluate the effects of occupational exposures to coke oven
      emissions (COEs) and benzo[a]pyrene (B[a]P) on the prevalence of hypertension and
      abnormal electrocardiogram (ECG) in coke oven workers. METHODS: We included 880
      coke oven workers and 710 oxygen employees in the exposed and control groups,
      respectively. Blood pressure (BP), ECG, blood lipid levels, and glucose levels of
      all subjects were measured. COE and B[a]P concentrations at the bottom, side, and
      top of the oven and control plants were estimated by weighing and high
      performance liquid chromatography. RESULTS: The COE concentration at the top and
      side was higher than that at the bottom (P < 0.05). The levels of B[a]P at the
      top and side significantly exceeded the limit value. Abnormal BP, ECG, the
      detection ratio of hypertension and left ventricular high voltage were
      significantly greater in the exposed group than in the control group (P < 0.05).
      The logistic regression analysis results revealed that age and B[a]P exposure
      were risk factors for hypertension in coke oven workers (P < 0.05) and both were
      risk factors for abnormal ECG (P < 0.05). Moreover, B[a]P exposure, age, and
      gender were risk factors for impaired fasting glucose in coke oven workers (P <
      0.05). CONCLUSIONS: B[a]P and COE exposures are risk factors for hypertension and
      abnormal ECG in coke oven workers.

PMID- 27885240
TI  - Incidence and characteristics of needlestick injuries among medical trainees at a
      community teaching hospital: A cross-sectional study.
AB  - OBJECTIVES: This field study aimed to determine the incidence and distribution of
      needlestick injuries among medical trainees at a community teaching hospital in
      Toronto, Canada. METHODS: The study was performed during the 2013-2015 academic
      years at Toronto East General Hospital (TEGH), a University of Toronto-affiliated
      community-teaching hospital during the 2013-2015 academic years. Eight-hundred
      and forty trainees, including medical students, residents, and post-graduate
      fellows, were identified and invited via email to participate in an anonymous
      online fluidsurveys.com survey of 16 qualitative and quantitative questions.
      RESULTS: Three-hundred and fifty trainees responded (42% response rate). Eighty
      eight (25%) respondents reported experiencing at least one injury at TEGH. In
      total, our survey identified 195 total injuries. Surgical trainees were
      significantly more likely to incur injuries than non-surgical trainees (IRR =
      3.03, 95% CI 1.80-5.10). Orthopaedic surgery trainees had the highest risk of a
      needlestick injury, being over 12 times more likely to be injured than emergency
      medicine trainees (IRR = 12.4, 95% CI 2.11-72.32). Only 28 of the 88 most recent
      needlestick injuries were reported to occupational health. Trainees reported a
      perception of insignificant risk, lack of resources and support for reporting,
      and injury stigmatization as reasons for not reporting needlestick injuries.
      CONCLUSIONS: Needlestick injuries were a common underreported risk to medical
      trainees at TEGH. Future research should investigate strategies to reduce injury
      and improve reporting among the high-risk and reporting-averse trainees.

PMID- 27885242
TI  - Occupational noise-induced hearing loss in auto part factory workers in welding
      units in Thailand.
AB  - OBJECTIVES: Most workers in auto part factories in Thailand are usually exposed
      to excessive noise in their workplace. This study aimed to assess the level of
      occupational noise-induced hearing loss and investigate risk factors causing
      hearing loss in auto part factory workers in the welding units in Thailand.
      METHODS: This was a cross-sectional study. One hundred eighty subjects were
      recruited from 356 workers in the welding unit of three factories. Sixty eligible
      subjects in each factory were selected by systemic random sampling. The subjects
      were interviewed using a face-to-face questionnaire. Noise exposure levels and
      audiograms were measured by a noise dosimeter and an audiometer, respectively.
      RESULTS: The findings confirmed that noise exposure levels of 86-90 dB (A) and
      exceeding 90 dB (A) significantly increased the risk of hearing loss in either
      ear. A noise exposure level exceeding 90 dB (A) significantly increased the
      prevalence of hearing loss in both ears. Regarding, a 10-pack-year smoking
      history increased the prevalence of hearing loss in either ear or both ears. In
      addition, subjects with employment duration exceeding 10 years significantly
      developed hearing loss in either ear. CONCLUSIONS: The engineering control or
      personal control by wearing hearing protection device should be used to decrease
      noise exposure levels lower than 85 dB (A) for 8 h. Moreover, if the exposure
      level reaches 85 dB (A) for 8 h, the employer needs to implement a hearing
      conservation program in the workplace.

PMID- 27885243
TI  - Di-n-butyl phthalate induced hypospadias relates to autophagy in genital tubercle
      via the PI3K/Akt/mTOR pathway.
AB  - OBJECTIVE: To explore the mechanisms of hypospadias induced by in utero exposure
      to din-butyl phthalate (DBP). METHODS: Timed-pregnant Sprague-Dawley rats were
      administered 750 mg/kg of DBP by gavage from GD (gestation days) 13 to GD 18,
      whereas control group received corn oil. Genital tubercles (GTs) and blood
      samples were collected from male fetuses on GD 19. The serum testosterone
      concentration, apoptosis activity, autophagosomes and their related proteins
      (light chain 3 (LC3-I, LC3-II) ), and sequestosomes (SQSTM1/p62) in the GTs were
      then measured. Protein expression of protein kinase B (Akt), Beclin 1,
      phosphorylated Akt (p-Akt), p-S6, and phosphorylated mammalian target of
      rapamycin (p-mTOR) in the GTs were analyzed by Western blotting. RESULTS: The
      incidence of hypospadias induced by DBP was 43.64% in male fetuses. The GT volume
      and GT volume/body weight of fetuses were significantly reduced in the
      hypospadias and the non-hypospadias groups. Apoptotic cell number was
      significantly decreased in the GTs of the hypospadias group, but unchanged in the
      non-hyposadias group. The ratio of LC3-II/LC3-I was higher in the GTs from DBP
      exposed fetuses compared to the control group. The ratio of LC3-II/LC3-I in the
      GTs was higher in the hypospadias group than in the non-hypospadias group. The
      number of autophagosomes was increased in the GTs of the hypospadias group.
      Protein expression of p-S6, p-mTOR, and p-Akt were significantly decreased in the
      GTs of hypospadiac rats. CONCLUSIONS: DBP-induced hypospadias might be associated
      with apoptosis and autophagy mediated by the PI3K/Akt/mTOR signaling pathway in
      the GT.

PMID- 27885244
TI  - Internal consistency, convergent validity, and structural validity of the
      Japanese version of the Physical Activity Self-Regulation scale (PASR-12) among
      Japanese workers: A validation study.
AB  - OBJECTIVES: Self-regulation for physical activity is considered as one of the
      most effective factors in promoting physical activity. However, there is no
      reliable and valid scale to measure it in Japanese. The purpose of this study was
      to investigate the internal consistency, convergent validity, and structural
      validity of the newly developed Japanese version of the 12-item Physical Activity
      Self-Regulation scale (PASR-12) among Japanese workers. METHODS: A cross
      sectional Internet-based survey recruiting 516 Japanese workers was conducted in
      Japan. The PASR-12 was translated according to the International Society of
      Pharmacoeconomics and Outcomes Research (ISPOR) task force guidelines. Physical
      activity and self-efficacy for physical activity were measured as comparisons for
      convergent validity. We calculated Cronbach's alphas, and conducted correlational
      analyses and confirmatory factor analysis (CFA). RESULTS: Of 516 workers, 485
      workers were eligible for all analyses. Cronbach's alpha for the scale scores
      ranged from 0.79 to 0.95. The scores of the total and 6 factor scales of the
      Japanese version of the PASR-12 had small-to-moderate positive correlations with
      the total physical activity and self-efficacy. Moreover, the 6-factor
      hypothesized model demonstrated excellent fit (chi2 (39) = 100.74, CFI = 0.973,
      RMSEA = 0.057). CONCLUSIONS: The Japanese version of the PASR-12 showed good
      reliability and factor-based and construct validity. Therefore, this scale could
      be applied to assess self-regulation for physical activity among Japanese
      workers.

PMID- 27885246
TI  - The association between subjective socioeconomic status and health inequity in
      victims of occupational accidents in Korea.
AB  - OBJECTIVES: We aimed to investigate the health inequity of victims of
      occupational accidents through the association between socioeconomic status and
      unmet healthcare need. METHODS: Data from the first and second Panel Study of
      Workers' Compensation Insurance were used, which included 1,803 participants. The
      odds ratio and 95% confidence intervals for the unmet healthcare needs of
      participants with a lower socioeconomic status and other socioeconomic statuses
      were investigated using multivariate regression analysis. RESULTS: Among all
      participants, 103 had unmet healthcare needs, whereas 1,700 did not. After
      adjusting for sex, age, smoking, alcohol, chronic disease, recuperation duration,
      accident type, disability, and economic participation, the odds ratio of unmet
      healthcare needs in participants with a lower socioeconomic status was 2.04 (95%
      confidence interval 1.32-3.15) compared to participants with other socioeconomic
      statuses. CONCLUSIONS: The victims of occupational accidents who have a lower
      socioeconomic status are more likely to have unmet healthcare needs in comparison
      to those with other socioeconomic statuses.

PMID- 27885245
TI  - Personal lifestyle as a resource for work engagement.
AB  - OBJECTIVES: Personal lifestyle, including diet, exercise, and sleep, might have
      an impact on work engagement, though previous studies have not focused on these
      relationships. The aim of this study was to examine whether dietary intake of
      fish, regular exercise, sufficient sleep, abstinence from alcohol, and abstinence
      from tobacco were positively associated with work engagement. METHODS: We
      recruited adults aged 40-74 years who attended the health checkups with a
      particular focus on the metabolic syndrome in central Tokyo. In December 2015,
      797 people responded to a questionnaire and 592 (74.3%) who had regular jobs were
      selected for this study. Work engagement was assessed on the 9-item Utrecht Work
      Engagement Scale (UWES-9). Bivariate and multivariate regression analyses were
      performed to examine the relationships between lifestyle and UWES-9. RESULTS:
      Dietary intake of fish, regular exercise, sufficient sleep, and abstinence from
      tobacco were significantly correlated with the total UWES-9 score, even after
      adjusting for age, sex, and depressive and anxiety symptoms. The results
      suggested a dose-response relationship between dietary fish intake and work
      engagement. CONCLUSIONS: Dietary fish intake, regular exercise, sufficient sleep,
      and abstinence from tobacco might be lifestyle factors that can serve as
      resources for work engagement. These findings could be useful in motivating
      employees to make lifestyle improvements and convincing employers and managers
      that lifestyle is important not only for health but also for productivity.

PMID- 27885247
TI  - Effects of web-based stress and depression literacy intervention on improving
      work engagement among workers with low work engagement: An analysis of secondary
      outcome of a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this randomized, controlled trial was to examine the
      effects of a psychoeducational information website on improving work engagement
      among individual workers with low work engagement, where work engagement was
      measured as a secondary outcome. METHODS: Participants were recruited from
      registered members of a web survey site in Japan. Participants who fulfilled the
      eligibility criteria were randomly allocated to intervention or control groups.
      Immediately after the baseline survey, the intervention group was invited to
      study a psychoeducational website called the "UTSMed," which provided general
      mental health literacy and cognitive behavioral skills. Work engagement was
      assessed by using the Utrecht Work Engagement Scale at baseline, 1-, and 4-month
      follow-ups for both intervention and control groups. An exploratory analysis was
      conducted for a subgroup with low (lower than the median scores) work engagement
      scores at baseline. RESULTS: A total of 1,236 workers completed the baseline
      survey. In the low work engagement subgroup, a total of 313 and 300 participants
      were allocated to an intervention and control group, respectively. In the high
      work engagement subgroup, 305 and 318 participants were allocated to an
      intervention and control group, respectively. The program showed a significant
      effect on work engagement (t = 1.98, P = 0.048) at the 4-month follow-up in the
      low work engagement subgroup, with a small effect size (d = 0.17). CONCLUSION: A
      web-based psychoeducation resource of mental health literacy and cognitive
      behavioral skills may be effective for improving work engagement among individual
      workers with low work engagement.

PMID- 27885248
TI  - Rs3842530 Polymorphism in MicroRNA-205 Host Gene in Lung and Breast Cancer
      Patients.
AB  - BACKGROUND The expression of miR-205 is closely related to the occurrence,
      development, and prognosis of lung cancer and breast cancer. However, studies
      show that it plays opposite roles in different tumor types. Because the
      expression and regulation of miR-205 are primarily confined to epigenetic areas,
      whether genetic variation of miR-205 is related to the occurrence or to the
      development of tumors has not been reported. The aim of this study was to screen
      genetic variation of miR-205 gene and to investigate its association with the
      risk and development of lung and breast cancer. MATERIAL AND METHODS Genomic DNA
      was extracted from cultured tumor cell lines and formalin-fixed and paraffin
      embedded lung and breast tissue samples. Bisulfite Clone Sequencing (BCS) and qRT
      PCR were employed to detect the DNA methylation status and gene expression of the
      miR-205 gene, respectively. Genetic variation of miR-205 and miR-205HG were
      genotyped with PCR-sequencing method. Immunohistochemical analysis for ER, PR,
      and HER2 was performed on breast tissue samples. RESULTS These results indicate
      that the functional association of rs3842530 in miR-205HG and lung cancer might
      provide a possible explanation for the tissue-dependent function of miR-205 in
      different tumors. CONCLUSIONS These results indicate that the functional
      association of rs3842530 in miR-205HG and lung cancer might provide a possible
      explanation for the tissue-dependent function of miR-205 in different tumors.

PMID- 27885249
TI  - Lactation-Related MicroRNA Expression in Microvesicles of Human Umbilical Cord
      Blood.
AB  - BACKGROUND The complex process by which lactation is initiated upon neonate
      delivery remains incompletely understood. Microvesicles (MVs) can transmit
      microRNAs (miRNAs) into recipient cells to influence cell function, and recent
      studies have identified miRNAs essential for mammary gland development and
      lactation. This study aimed to investigate the expression of lactation-related
      miRNAs in MVs isolated from human umbilical cord blood immediately after
      delivery. MATERIAL AND METHODS Umbilical cord blood samples were collected from
      70 healthy pregnant women, and MVs were isolated through differential
      centrifugation and characterized by transmission electron microscopy, Western
      blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were
      screened using bioinformatics tools for miRNA target prediction, gene ontology,
      and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression
      analysis, and the results were validated by real-time PCR. Upon exposure of HBL
      100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence
      confocal microscopy and b-casein secretion was detected by ELISA. RESULTS
      Spherical MVs extracted from umbilical cord blood expressed CD63 and had an
      average diameter of 167.0+/-77.1 nm. We profiled 337 miRNAs in human umbilical
      cord blood MVs and found that 85 were related to lactation by bioinformatics
      analysis. The 25 most differentially expressed lactation-related miRNAs were
      validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture,
      and significantly increased secretion of beta-casein was observed after 96 h from
      cells exposed to MVs (P<0.05). CONCLUSIONS Umbilical cord blood MVs contain many
      lactation-related miRNAs and can induce beta-casein production by HBL-100 cells
      in vitro. Thus, umbilical cord blood MVs may mediate secretion of beta-casein
      through miRNAs, thereby playing an important role in fetal-maternal crosstalk.

PMID- 27885250
TI  - CXC Chemokine Receptor 4 (CXCR4) Antagonist, a Novel Pathway to Prevent Chronic
      Allograft Nephropathy.
AB  - BACKGROUND Chronic allograft nephropathy (CAN) remains a major problem for long
      term graft survival and different pathways participate in its development. CXC
      chemokine receptor 4 (CXCR4) is significantly upregulated following renal injury
      and fibrotic response. We investigated the effect of AMD3100, a CXCR4 antagonist,
      on the development of CAN in rat models. MATERIAL AND METHODS CAN rat models
      (n=20) were established using male Fisher 344 to Lewis rats. Rats in the
      experimental group (n=10) were treated with AMD3100 (1 mg/kg/day subcutaneously,
      0-12 weeks), rats in the control group (n=10) were treated with saline. The serum
      creatinine levels were monitored every week. Kidney grafts were harvested 12
      weeks after modeling for histological analysis. We used chronic allograft damage
      index (CADI) scores to evaluate each group. Q-PCR and Western blotting were used
      to measure CXCR4, TGF-beta1/Smad3 signaling pathway and alpha-smooth muscle actin
      (alpha-SMA) expression in renal allograft tissue. RESULTS CXCR4 expression was
      increased significantly in the control group which developed intense chronic
      changes after 12 weeks. Histological changes of CAN in the experimental group
      were ameliorated by AMD3100 which also had better graft function compare to the
      control group. AMD3100 significantly blunted the increase in the mRNA expression
      level of CXCR4, TGF-beta1/Smad3, and alpha-SMA. A significant reduction in TGF
      beta1 and alpha-SMA protein content was observed only in the experimental group
      as shown in a representative Western blot. CONCLUSIONS Based on these findings,
      CXCR4 expression may mediate in part the development of CAN. AMD3100 may
      ameliorate histological changes of CAN and maintain better allograft function. It
      blunts downstream effects of TGF-beta1 signaling and fibroblast activation.
      Therefore, antagonism of CXCR4 may provide a novel way to prevent the development
      of CAN.

PMID- 27885251
TI  - Postprandial and Orthostatic Hypotension Treated by Sitagliptin in a Patient with
      Dementia with Lewy Bodies.
AB  - BACKGROUND Postprandial hypotension, induced by an absorption of glucose from
      intestine, could be treated by acarbose; however, it was unclear whether
      dipeptidyl peptidase-4 inhibitor reduced postprandial hypotension. CASE REPORT A
      78-year-old woman who had experienced episodes of dizziness and hypotension after
      eating was admitted to our hospital. During 24-hour ambulatory blood pressure
      monitoring, there were repeated episodes of marked postprandial hypotension;
      i.e., a significant systolic blood pressure reduction within two hours after
      eating (from -58 to -64 mm Hg after meals). The patient was diagnosed with
      dementia with Lewy bodies. The patient exhibited postprandial hyperglycemia and
      hypotension after a 75 g oral glucose tolerance test. After the administration of
      25 mg sitagliptin, the patient's postprandial and orthostatic hypotension was
      reduced remarkably. Moreover, her Mini-Mental State Examination score
      subsequently increased (from 22 to 25 points). CONCLUSIONS The dipeptidyl
      peptidase-4 inhibitor sitagliptin can delay postprandial increases in glucose
      levels and hypotensive episodes, as well as sympathetic nervous system
      abnormalities and orthostatic hypotension.

PMID- 27885252
TI  - A Reliability Generalization Meta-analysis of the Leyton Obsessional Inventory
      Child Version Survey Form.
AB  - BACKGROUND: The Leyton Obsessional Inventory Child Version Survey Form (LOI-CV
      SF) is a scale created in order to detect obsessive-compulsive symptoms and their
      effects on the daily lives of children and adolescents from ages 10 to 18 and for
      the screening of non-clinic infant population. With the purpose of estimating the
      reliability of the test scores, and how it varies in relation to the
      characteristics of the studies, a meta-analysis of reliability generalization was
      carried out. METHODS: A meta-analysis was accomplished. An exhaustive research
      allowed to select 13 studies that reported some reliability estimate of the test
      scores and, through the KR-21 formula, this number was increased to 43
      estimations of internal consistency reliability. Taking these coefficients, an
      estimation of the average reliability and analyses of the variables that could be
      affecting the heterogeneity of reliability coefficients was accomplished.
      RESULTS: On average, the reliability by internal consistency of the symptom scale
      scores was 0.79 (95%CI:0.76 and 0.82), with minimum and maximum values of 0.52
      and 0.97, respectively. A large heterogeneity was found (I2 = 96%).The predictive
      model identified the standard deviation of tests scores as the most relevant
      variable. The analysis of moderator variables revealed that, mainly, the standard
      deviation of the test scores is the most statistically related to the
      reliability, presenting a positive relationship with it. CONCLUSIONS: The results
      of the LOI-CV-SF showed a satisfactory average reliability for research purposes,
      but not for clinical practice purposes.

PMID- 27885253
TI  - [Awareness, Treatment and Control of Hypertension in Population Aged 16 to 90
      Years Old in the Valencia Region, Spain, 2010].
AB  - OBJECTIVE: Hypertension is an important risk factor in terms of mortality
      attributable and the main modifiable cardiovascular risk factor. The aim of the
      study is to estimate the degree of awareness, treatment and control of
      hypertension in population of Valencia Region and identify predictors that
      explain the lack of proper control. 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. Automatic sphygmomanometer was used for taking
      blood pressure. Hypertension was defined according to the criteria of 2007
      European Society of Hypertension and the European Society of Cardiology. Data on
      knowledge and treatment were obtained by survey. Predictors for awareness,
      treatment and control of hypertension were estimated by logistic regression
      models. RESULTS: The prevalence of hypertension estimated for the study
      population was 38.2% (95% CI: 34.9%-41.5%). 51.4% (95% CI: 45.9%-57.0%) of the
      hypertensive population, knew his condition. 88.8% of them (95% CI: 83.9%-93.6%)
      were receiving drug therapy and of these, 45.1% (95% CI: 36.9%-53.3%) maintained
      blood pressure controlled. CONCLUSIONS: Since the last survey in Valencia Region,
      the degree of awareness of hypertension has not improved although an increase in
      those treated with antihypertensive drugs is observed.

PMID- 27885254
TI  - Aldehyde dehydrogenase is used by cancer cells for energy metabolism.
AB  - We found that non-small-cell lung cancer (NSCLC) cells express high levels of
      multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of
      metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical
      tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis,
      we found that multiple ALDH isozymes were generally abundant in NSCLC cells
      compared with their levels in normal IMR-90 human lung cells. As a result of the
      catalytic reaction mediated by ALDH, NADH is produced as a by-product from the
      conversion of aldehyde to carboxylic acid. We hypothesized that the NADH produced
      by ALDH may be a reliable energy source for ATP production in NSCLC. This study
      revealed that NADH production by ALDH contributes significantly to ATP production
      in NSCLC. Furthermore, gossypol, a pan-ALDH inhibitor, markedly reduced the level
      of ATP. Gossypol combined with phenformin synergistically reduced the ATP levels,
      which efficiently induced cell death following cell cycle arrest.

PMID- 27885256
TI  - Evolution of gossip-based indirect reciprocity on a bipartite network.
AB  - Cooperation can be supported by indirect reciprocity via reputation. Thanks to
      gossip, reputations are built and circulated and humans can identify defectors
      and ostracise them. However, the evolutionary stability of gossip is allegedly
      undermined by the fact that it is more error-prone that direct observation,
      whereas ostracism could be ineffective if the partner selection mechanism is not
      robust. The aim of this work is to investigate the conditions under which the
      combination of gossip and ostracism might support cooperation in groups of
      different sizes. We are also interested in exploring the extent to which errors
      in transmission might undermine the reliability of gossip as a mechanism for
      identifying defectors. Our results show that a large quantity of gossip is
      necessary to support cooperation, and that group structure can mitigate the
      effects of errors in transmission.

PMID- 27885255
TI  - TFAP2C-mediated upregulation of TGFBR1 promotes lung tumorigenesis and epithelial
      mesenchymal transition.
AB  - TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression
      has been positively correlated with poor prognosis in patients with certain types
      of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non
      small-cell lung cancer (NSCLC) are still unknown. We previously performed a
      microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming
      growth factor-beta receptor type 1) was found to be upregulated by TFAP2C. We
      observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such
      as cell viability, proliferation and cell cycle progression. TGFBR1 upregulation
      induced by TFAP2C also promoted cell motility and migration, leading to malignant
      development. We also found that PAK1 (p21 protein (Cdc42/Rac)-activated kinase 1)
      signaling was involved in TFAP2C/TGFBR1-induced tumorigenesis. These results were
      confirmed by an in vivo xenograft model and patient tissue samples. This study
      shows that TFAP2C promoted tumor progression by upregulation of TGFBR1 and
      consequent activation of PAK1 signaling.

PMID- 27885257
TI  - From Quasi-Planar B56 to Penta-Ring Tubular Ca(c)B56: Prediction of Metal
      Stabilized Ca(c)B56 as the Embryo of Metal-Doped Boron alpha-Nanotubes.
AB  - Motifs of planar metalloborophenes, cage-like metalloborospherenes, and metal
      centered double-ring tubular boron species have been reported. Based on extensive
      first-principles theory calculations, we present herein the possibility of doping
      the quasi-planar C2v B56 (A-1) with an alkaline-earth metal to produce the penta
      ring tubular Ca(c)B56 (B-1) which is the most stable isomer of the system
      obtained and can be viewed as the embryo of metal-doped (4,0) boron alpha
      nanotube Ca(c)BNT(4,0) (C-1). Ca(c)BNT(4,0) (C-1) can be constructed by rolling
      up the most stable boron alpha-sheet and is predicted to be metallic in nature.
      Detailed bonding analyses show that the highly stable planar C2v B56 (A-1) is the
      boron analog of circumbiphenyl (C38H16) in pi-bonding, while the 3D aromatic C4v
      Ca(c)B56 (B-1) possesses a perfect delocalized pi system over the sigma-skeleton
      on the tube surface. The IR and Raman spectra of C4v Ca(c)B56 (B-1) and
      photoelectron spectrum of its monoanion C4v Ca

PMID- 27885258
TI  - Circulating periostin in relation to insulin resistance and nonalcoholic fatty
      liver disease among overweight and obese subjects.
AB  - Recent study showed periostin play a pivotal role in abnormal liver triglyceride
      (TG) accumulation and in the development of obesity-related liver fat
      accumulation. However, little is known regarding whether periostin plays a key
      role in the heightened prevalence of NAFLD and other metabolic phenotypes among
      large-scale populations. A cross-sectional sample of 8850 subjects aged 40 yr or
      older from China were evaluated in this study. Serum periostin was measured by
      ELISA methods. The diagnosis of NAFLD by liver ultrasonic examination. Among
      overweight and obese subjects, NAFLD subjects had higher serum periostin levels
      than those without NAFLD (126.75 ng/ml vs. 75.96 ng/ml, p < 0.001). Periostin was
      associated with a higher risk for NAFLD (OR 1.75 for each SD increase in
      periostin, 95% CI 1.04-3.37, p < 0.001) among overweight and obese subjects after
      confounder adjustment. Furthermore, periostin levels among overweight and obese
      subjects were correlated with aspartate aminotransferase (r = 0.102, p = 0.004),
      alanine aminotransferase (r = 0.108, p = 0.003), waist circumference (r = 0.111,
      p = 0.002), homeostasis model assessment index-insulin resistance (r = 0.154, p <
      0.001) and fasting plasma insulin (r = 0.098, p = 0.006), TG (r = 0.117, p =
      0.001). Elevated circulating periostin level was associated with an increased
      risk of having NAFLD and insulin resistance among overweight and obese
      individuals.

PMID- 27885259
TI  - TrackNTrace: A simple and extendable open-source framework for developing single
      molecule localization and tracking algorithms.
AB  - Super-resolution localization microscopy and single particle tracking are
      important tools for fluorescence microscopy. Both rely on detecting, and
      tracking, a large number of fluorescent markers using increasingly sophisticated
      computer algorithms. However, this rise in complexity makes it difficult to fine
      tune parameters and detect inconsistencies, improve existing routines, or develop
      new approaches founded on established principles. We present an open-source
      MATLAB framework for single molecule localization, tracking and super-resolution
      applications. The purpose of this software is to facilitate the development,
      distribution, and comparison of methods in the community by providing a unique,
      easily extendable plugin-based system and combining it with a novel visualization
      system. This graphical interface incorporates possibilities for quick inspection
      of localization and tracking results, giving direct feedback of the quality
      achieved with the chosen algorithms and parameter values, as well as possible
      sources for errors. This is of great importance in practical applications and
      even more so when developing new techniques. The plugin system greatly simplifies
      the development of new methods as well as adapting and tailoring routines towards
      any research problem's individual requirements. We demonstrate its high speed and
      accuracy with plugins implementing state-of-the-art algorithms and show two
      biological applications.

PMID- 27885261
TI  - Curvature-driven bubbles or droplets on the spiral surface.
AB  - Directional motion of droplets or bubbles can often be observed in nature and our
      daily life, and this phenomenon holds great potential in many engineering areas.
      The study shows that droplets or bubbles can be driven to migrate perpetually on
      some special substrates, such as the Archimedean spiral, the logarithmic spiral
      and a cantilever sheet in large deflection. It is found that a bubble approaches
      or deviates from the position with highest curvature of the substrate, when it is
      on the concave or convex side. This fact is helpful to explain the repelling
      water capability of Nepenthes alata. Based on the force and energy analysis, the
      mechanism of the bubble migration is well addressed. These findings pave a new
      way to accurately manipulate droplet or bubble movement, which bring inspirations
      to the design of microfluidic and water harvesting devices, as well as oil
      displacement and ore filtration.

PMID- 27885260
TI  - Nitric oxide triggers a transient metabolic reprogramming in Arabidopsis.
AB  - Nitric oxide (NO) regulates plant growth and development as well as responses to
      stress that enhanced its endogenous production. Arabidopsis plants exposed to a
      pulse of exogenous NO gas were used for untargeted global metabolomic analyses
      thus allowing the identification of metabolic processes affected by NO. At early
      time points after treatment, NO scavenged superoxide anion and induced the
      nitration and the S-nitrosylation of proteins. These events preceded an extensive
      though transient metabolic reprogramming at 6 h after NO treatment, which
      included enhanced levels of polyamines, lipid catabolism and accumulation of
      phospholipids, chlorophyll breakdown, protein and nucleic acid turnover and
      increased content of sugars. Accordingly, lipid-related structures such as root
      cell membranes and leaf cuticle altered their permeability upon NO treatment.
      Besides, NO-treated plants displayed degradation of starch granules, which is
      consistent with the increased sugar content observed in the metabolomic survey.
      The metabolic profile was restored to baseline levels at 24 h post-treatment,
      thus pointing up the plasticity of plant metabolism in response to nitroxidative
      stress conditions.

PMID- 27885262
TI  - Comparison of the effect on bone healing process of different implants used in
      minimally invasive plate osteosynthesis: limited contact dynamic compression
      plate versus locking compression plate.
AB  - Minimally invasive plate osteosynthesis (MIPO) has been widely accepted because
      of its satisfactory clinical outcomes. However, the implant construct that works
      best for MIPO remains controversial. Different plate designs result in different
      influence mechanisms to blood flow. In this study, we created ulnar fractures in
      42 beagle dogs and fixed the fractures using MIPO. The dogs were randomly divided
      into two groups and were fixed with a limited contact dynamic compression plate
      (LC-DCP) or a locking compression plate (LCP). Our study showed that with MIPO,
      there was no significant difference between the LCP and the LC-DCP in terms of
      fracture fixation, bone formation, or mineralization. Combined with the previous
      literature, we inferred that the healing process is affected by the quality of
      fracture reduction more than plate selection.

PMID- 27885263
TI  - Targeting High Dynamin-2 (DNM2) Expression by Restoring Ikaros Function in Acute
      Lymphoblastic Leukemia.
AB  - Dynamin-2 (DNM2) is a GTPase essential for intracellular vesicle formation and
      trafficking, cytokinesis and receptor endocytosis. Mutations in DNM2 are common
      in early T-cell precursor acute lymphoblastic leukemia. However, DNM2 expression
      in other types of ALL are not reported. We studied DNM2 mRNA level in adults with
      B- and T-cell ALL. We found DNM2 is more highly expressed compared with normals
      in both forms of ALL. High DNM2 expression is associated with some clinical and
      laboratory features, inferior outcomes and with leukaemia cell proliferation. We
      also found Ikaros directly binds the DNM2 promoter and suppresses DNM2
      expression. Consequently IKZF1 deletion is associated with high DNM2 expression.
      Conversely, casein kinase-2 (CK2)-inhibitor increases Ikaros function thereby
      inhibiting DNM2 expression. Inhibiting DNM2 suppresses proliferation of leukemia
      cells and synergizes with CK2 inhibition. Our data indicate high DNM2 expression
      is associated with Ikaros dysregulation and may be important in the development
      of B-ALL.

PMID- 27885266
TI  - Electrospray deposition device used to precisely control the matrix crystal to
      improve the performance of MALDI MSI.
AB  - MALDI MSI has been recently applied as an innovative tool for detection of
      molecular distribution within a specific tissue. MALDI MSI requires deposition of
      an organic compound, known as matrix, on the tissue of interest to assist analyte
      desorption and ionization, in which the matrix crystal homogeneity and size
      greatly influence the imaging reproducibility and spatial resolution in MALDI
      MSI. In this work, a homemade electrospray deposition device was developed for
      deposition of matrix in MALDI MSI. The device could be used to achieve 1 MUm
      homogeneous matrix crystals in MALDI MSI analysis. Moreover, it was found, for
      the first time, that the electrospray deposition device could be used to
      precisely control the matrix crystal size, and the imaging spatial resolution was
      increased greatly as the matrix crystals size becoming smaller. In addition, the
      easily-built electrospray deposition device was durable for acid, base or organic
      solvent, and even could be used for deposition of nanoparticles matrix, which
      made it unparalleled for MALDI MSI analysis. The feasibility of the electrospray
      deposition device was investigated by combination with MALDI FTICR MSI to analyze
      the distributions of lipids in mouse brain and liver cancer tissue section.

PMID- 27885264
TI  - Deciphering the divergent roles of progestogens in breast cancer.
AB  - Most breast cancers are driven by oestrogen receptor-alpha. Anti-oestrogenic
      drugs are the standard treatment for these breast cancers; however, treatment
      resistance is common, necessitating new therapeutic strategies. Recent
      preclinical and historical clinical studies support the use of progestogens to
      activate the progesterone receptor (PR) in breast cancers. However, widespread
      controversy exists regarding the role of progestogens in this disease, hindering
      the clinical implementation of PR-targeted therapies. Herein, we present and
      discuss data at the root of this controversy and clarify the confusion and
      misinterpretations that have consequently arisen. We then present our view on how
      progestogens may be safely and effectively used in treating breast cancer.

PMID- 27885267
TI  - Contributory roles of two l-lactate dehydrogenases for l-lactic acid production
      in thermotolerant Bacillus coagulans.
AB  - Thermotolerant Bacillus coagulans is considered to be a more promising producer
      for bio-chemicals, due to its capacity to withstand harsh conditions. Two L
      lactate dehydrogenase (LDH) encoding genes (ldhL1 and ldhL2) and one D-LDH
      encoding gene (ldhD) were annotated from the B. coagulans DSM1 genome.
      Transcriptional analysis revealed that the expression of ldhL2 was undetectable
      while the ldhL1 transcription level was much higher than that of ldhD at all
      growth phases. Deletion of the ldhL2 gene revealed no difference in fermentation
      profile compared to the wild-type strain, while ldhL1 single deletion or
      ldhL1ldhL2 double deletion completely blocked L-lactic acid production.
      Complementation of ldhL1 in the above knockout strains restored fermentation
      profiles to those observed in the wild-type strain. This study demonstrates ldhL1
      is crucial for L-lactic acid production and NADH balance in B. coagulans DSM1 and
      lays the fundamental for engineering the thermotolerant B. coagulans strain as a
      platform chemicals producer.

PMID- 27885265
TI  - The disparate origins of ovarian cancers: pathogenesis and prevention strategies.
AB  - Ovarian cancer is the fifth cause of cancer-related death in women and comprises
      a histologically and genetically broad range of tumours, including those of
      epithelial, sex cord-stromal and germ cell origin. Recent evidence indicates that
      high-grade serous ovarian carcinoma, clear cell carcinoma and endometrioid
      carcinoma primarily arise from tissues that are not normally present in the
      ovary. These histogenetic pathways are informing risk-reduction strategies for
      the prevention of ovarian and ovary-associated cancers and have highlighted the
      importance of the seemingly unique ovarian microenvironment.

PMID- 27885268
TI  - Loss-induced Enhanced Transmission in Anisotropic Density-near-zero Acoustic
      Metamaterials.
AB  - Anisotropic density-near-zero (ADNZ) acoustic metamaterials are investigated
      theoretically and numerically in this paper and are shown to exhibit
      extraordinary transmission enhancement when material loss is induced. The
      enhanced transmission is due to the enhanced propagating and evanescent wave
      modes inside the ADNZ medium thanks to the interplay of near-zero density,
      material loss, and high wave impedance matching in the propagation direction. The
      equi-frequency contour (EFC) is used to reveal whether the propagating wave mode
      is allowed in ADNZ metamaterials. Numerical simulations based on plate-type
      acoustic metamaterials with different material losses were performed to
      demonstrate collimation and subwavelength imaging enabled by the induced loss in
      ADNZ media. This work provides a different way for manipulating acoustic waves.

PMID- 27885269
TI  - PbS Colloidal Quantum Dot Photodetectors operating in the near infrared.
AB  - Colloidal quantum dots have recently attracted lot of interest in the fabrication
      of optoelectronic devices due to their unique optical properties and their simple
      and low cost fabrication. PbS nanocrystals emerged as the most advanced colloidal
      material for near infrared photodetectors. In this work we report on the
      fabrication and characterization of PbS colloidal quantum dot photoconductors. In
      order to make devices suitable for the monolithic integration with silicon
      electronics, we propose a simple and low cost process for the fabrication of
      photodetectors and investigate their operation at very low voltage bias. Our
      photoconductors feature high responsivity and detectivity at 1.3 MUm and 1 V bias
      with maximum values of 30 A/W and 2.1010 cmHz1/2W-1, respectively. Detectivity
      close to 1011 cmHz1/2W-1 has been obtained resorting to bridge sensor readout.

PMID- 27885270
TI  - GDP per capita and obesity prevalence worldwide: an ambiguity of effects
      modification.

PMID- 27885271
TI  - p53 pathway dysfunction is highly prevalent in acute myeloid leukemia independent
      of TP53 mutational status.
AB  - TP53 mutations are associated with the lowest survival rates in acute myeloid
      leukemia (AML). In addition to mutations, loss of p53 function can arise via
      aberrant expression of proteins that regulate p53 stability and function. We
      examined a large AML cohort using proteomics, mutational profiling and network
      analyses, and showed that (1) p53 stabilization is universal in mutant TP53
      samples, it is frequent in samples with wild-type TP53, and in both cases
      portends an equally dismal prognosis; (2) the p53 negative regulator Mdm2 is
      frequently overexpressed in samples retaining wild-type TP53 alleles, coupled
      with absence of p21 expression and dismal prognosis similar to that of cases with
      p53 stabilization; (3) AML samples display unique patterns of p53 pathway protein
      expression, which segregate prognostic groups with distinct cure rates; (4) such
      patterns of protein activation unveil potential AML vulnerabilities that can be
      therapeutically exploited.

PMID- 27885272
TI  - Driver mutations' effect in secondary myelofibrosis: an international multicenter
      study based on 781 patients.

PMID- 27885274
TI  - Multicolor Colormetric Biosensor for the Determination of Glucose based on the
      Etching of Gold Nanorods.
AB  - In this work, 3,3',5,5'-tetramethylbenzidine(II) (TMB2+), derived from H2O2
      horseradish peroxidase (HRP)-3,3',5,5'-tetramethylbenzidine (H2O2-HRP-TMB)
      reaction system, was used to etch AuNRs to generate different colors of solution.
      Many enzyme reactions are involved in the production of H2O2 (e.g., glucose can
      react with the dissolved oxygen in the presence of glucose oxidase (GOx) to
      produce H2O2). Given this information, a simple visual biosensor was developed in
      this study, with glucose as the example target. The detection range of the
      proposed system varied with the experimental conditions, such as the
      concentration of GOx and HRP, and enzymatic reaction time. Under the optimized
      conditions, the longitudinal shift of localized surface plasmon resonances (LSPR)
      had a linear correlation with the glucose concentration in the range of 0.1~1.0
      mM. Meanwhile, the solution displayed a specific color in response to the glucose
      concentration, thus enabling the visual quantitative detection of glucose at a
      glance. Compared with the traditional monochromic colorimetry, this multicolor
      glucose sensor generates various vivid colors, which can be easily distinguished
      by naked eyes without any sophisticated instrument. Notably, the proposed method
      has been successfully applied to detect glucose in serum samples with satisfied
      results.

PMID- 27885273
TI  - Fatty acid-binding protein FABP4 mechanistically links obesity with aggressive
      AML by enhancing aberrant DNA methylation in AML cells.
AB  - Obesity is becoming more prevalent worldwide and is a major risk factor for
      cancer development. Acute myeloid leukemia (AML), the most common acute leukemia
      in adults, remains a frequently fatal disease. Here we investigated the molecular
      mechanisms by which obesity favors AML growth and uncovered the fatty acid
      binding protein 4 (FABP4) and DNA methyltransferase 1 (DNMT1) regulatory axis
      that mediates aggressive AML in obesity. We showed that leukemia burden was much
      higher in high-fat diet-induced obese mice, which had higher levels of FABP4 and
      interleukin (IL)-6 in the sera. Upregulation of environmental and cellular FABP4
      accelerated AML cell growth in both a cell-autonomous and cell-non-autonomous
      manner. Genetic disruption of FABP4 in AML cells or in mice blocked cell
      proliferation in vitro and induced leukemia regression in vivo. Mechanistic
      investigations showed that FABP4 upregulation increased IL-6 expression and
      signal transducer and activator of transcription factor 3 phosphorylation leading
      to DNMT1 overexpression and further silencing of the p15INK4B tumor-suppressor
      gene in AML cells. Conversely, FABP4 ablation reduced DNMT1-dependent DNA
      methylation and restored p15INK4B expression, thus conferring substantial
      protection against AML growth. Our findings reveal the FABP4/DNMT1 axis in the
      control of AML cell fate in obesity and suggest that interference with the
      FABP4/DNMT1 axis might be a new strategy to treat leukemia.

PMID- 27885275
TI  - TDB protects vascular endothelial cells against oxygen-glucose
      deprivation/reperfusion-induced injury by targeting miR-34a to increase Bcl-2
      expression.
AB  - Prolonged ischemia can result in apoptotic death of vascular endothelial cells
      and lead to ischemic vascular diseases including vascular dementia,
      arteriosclerosis and brain oedema. Finding protective strategies to prevent this
      is therefore an urgent mission. Recent studies have shown that dysregulation of
      microRNAs (miRNAs) can lead to imbalance of Bcl-2 family proteins and
      mitochondrial dysfunction, leading to further damage of vascular cells under
      ischemic conditions. However, whether miRNAs can be used as a drug target for
      treating vascular diseases is not fully understood. In this study, we observed
      that the natural product 2,4,5-trihydroxybenzaldehyde (TDB) could effectively
      inhibit vascular cell apoptosis following oxygen-glucose deprivation/reperfusion
      (OGD/R) by maintaining mitochondrial membrane potential (MMP) and suppressing
      activation of the mitochondria-dependent caspase-9/3 apoptosis pathway.
      Furthermore, we identified miR-34a, a crucial negative regulator of Bcl-2, as a
      target for the protective effect of TDB on vascular cells. TDB-induced
      suppression of miR-34a resulted in a significant upregulation of Bcl-2 protein,
      MMP maintenance, and the survival of vascular cells following OGD/R. Our findings
      suggest that targeting miR-34a with the natural product TDB may provide a novel
      strategy for the treatment of ischemic vascular injuries, and demonstrate the
      therapeutic potential in targeting miRNAs using appropriate small molecules.

PMID- 27885277
TI  - T cells: A tissue checkpoint for TH2s.

PMID- 27885278
TI  - Infection: Interferons suppress antibody responses.

PMID- 27885279
TI  - Macrophages: Macrophage muscle man.

PMID- 27885280
TI  - Infection: Zika virus: end of transmission?

PMID- 27885281
TI  - Macrophages: Granuloma macrophage differentiation.

PMID- 27885276
TI  - Immunoregulation by members of the TGFbeta superfamily.
AB  - The transforming growth factor-beta (TGFbeta) superfamily is encoded by 33 genes
      and includes TGFbeta, bone morphogenetic proteins (BMPs) and activins. Although
      TGFbeta is well recognized as a crucial regulator of immune responses, the
      immunoregulatory functions of other TGFbeta family members are less clear.
      However, recent evidence suggests that BMPs and activins have important roles in
      regulating immune responses. In this Review, we briefly outline the signalling
      pathways of the TGFbeta superfamily and discuss new insights into the
      immunoregulatory functions of BMPs and activins in the context of infection,
      inflammation and cancer.

PMID- 27885282
TI  - Genome-wide association studies of drug response and toxicity: an opportunity for
      genome medicine.

PMID- 27885284
TI  - Snakebite in Nepal: Neglected Public Health Challenge.

PMID- 27885285
TI  - Emergence of Aminoglycoside Resistance Due to armA methylase in Multi-drug
      Resistant Acinetobacter Baumannii Isolates in a University Hospital in Nepal.
AB  - BACKGROUND: The emergence of multidrug-resistant Acinetobacter baumannii
      associated with hospital-acquired infections has been increasingly reported
      worldwide. 16S rRNA methylase producing Gram-negative bacteria are highly
      resistant to all clinically important aminoglycosides. We analyzed A. baumannii
      clinical isolates resistant to aminoglycosides from hospitalized patients. The
      objective of this study was to investigate the emergence of armA in A.baumannii
      species associated with nosocomial infection in a university hospital in Nepal.
      METHODS: This was a cross-sectional study conducted at the department of Clinical
      Microbiology, Tribhuvan University Teaching Hospital (TUTH), from December 2013
      to December 2014. A total of 246 Acinetobacter species were isolated from
      different patients were screened for MDR A. baumannii. Identification at the
      species level was confirmed by 16S rRNA sequencing. Drug susceptibility testing
      was performed by Kirby- Bauer disc diffusion method and minimum inhibitory
      concentrations (MICs) were determined using the guidelines of the Clinical and
      Laboratory Standards Institute (CLSI). Screening for 16S rRNA methylase
      production was done for the isolates resistant to gentamicin and amikacin.
      Detection of 16S rRNA methylase gene was done by PCR. RESULTS: All 122 multidrug
      resistant A. baumanniiisolates were resistant to majority of the antibiotics used
      except polymyxin and tigecycline. Ninty-six MDR A. baumannii isolates had MICs of
      > 512 mg/L to amikacin and arbekacin indicating their high resistance to
      aminoglycosides.Of the 96 pan-aminoglycoside resistant isolates, 75 isolates had
      16SrRNAmethylasewith all isolates harboring armA gene. CONCLUSIONS: This is the
      first report describing multidrug-resistant A. baumannii strains harboring armA
      from hospitalized patients in Nepal. A methylase gene (armA), conferring high
      level of resistance to aminoglycosides, was detected in majority of our isolates.

PMID- 27885286
TI  - Immediate Outcome of Hypoxic Ischaemic Encephalopathy in Hypoxiate Newborns in
      Nepal Medical College.
AB  - BACKGROUND: Birth asphyxia is the fifth major cause of under-five child deaths
      after pneumonia, diarrhoea, neonatal infections and complications of preterm
      birth. It is one of the important causes of neonatal mortality and morbidity
      accounting up to 30% of neonatal death in Nepal. It is also an important cause of
      long-term neurological disability and impairment. The mortality rate due to birth
      asphyxia is considered a good guide to the quality of perinatal care. This study
      was conducted to assess the rate of birth asphyxia, risk factors and outcome of
      the babies who were asphyxiated at birth. METHODS: A prospective study was
      conducted during the period of one year from April 2013 to March 2014 in Nepal
      Medical College. All the term babies born during the period with APGAR score at 5
      minutes of < 7 were considered to have birth asphyxia and included in the study.
      Details of maternal risk factors during pregnancy and labor were analyzed. The
      newborn babies were assessed for clinical features of hypoxic ischemic
      encephalopathy (HIE) and its immediate outcome. RESULTS: Out of 2226 live births,
      47 (15.9%) newborns had birth asphyxia with the rate of 21.1/1000 live births.
      The mortality rate due to birth asphyxia was 4.25%. Meconium stained liquor was
      present in 31(65.96%) cases during delivery and prolonged rupture of membrane in
      7(14.89%). CONCLUSIONS: Early identification and close monitoring of high-risk
      mothers with maintaining partograph during labor help to reduce birth asphyxia.

PMID- 27885287
TI  - Comparative Study of Prevalence of Cataract at High Altitude and Kathmandu
      Valley.
AB  - BACKGROUND: Cataract is the leading cause of avoidable blindness in the world.
      Many etiological and risk factors for age related cataract has been documented.
      The present study is conducted to compare the prevalence of cataract at high
      altitude and Kathmandu valley.Many etiological and risk factors for age related
      cataract has been documented. METHODS: A cross sectional comparative study was
      conducted at Jomsom, Kagbeni, Jharkot and Muktinath of Mustang district and
      Balaju and Jawalakhel of Kathmandu valley of Nepal in 2009 to 2011 . There were
      222 participants at Mustang and186 participants at Kathmandu. The prevalence of
      cataract was studied among the Tibetans and Thakali population at Mustang and
      Tibetans at Jawalakhel and Thakali population at Balaju of Kathmandu valley.
      RESULTS: Prevalence of cataract at high altitude was 31.5% and 10.2% at Kathmandu
      valley. The prevalence of cataract is 4.05 times more at high altitude as
      compared to Kathmandu valley (p value < 0.001). CONCLUSIONS: The prevalence of
      cataract was significantly high at high altitude as compared to lower altitude.

PMID- 27885288
TI  - Correlation between Clinical Features and Magnetic Resonance Imaging Findings in
      Lumbar Disc Prolapse.
AB  - BACKGROUND: Magnetic resonance imaging is routinely done for diagnosis of lumbar
      disc prolapse. Many abnormalities of disc are observed even in asymptomatic
      patient.This study was conducted tocorrelate these abnormalities observed on
      Magnetic resonance imaging and clinical features of lumbar disc prolapse.
      METHODS: A This prospective analytical study includes 57 cases of lumbar disc
      prolapse presenting to Department of Orthopedics, Tribhuvan University Teaching
      Hospital from March 2011 to August 2012. All patientshad Magnetic resonance
      imaging of lumbar spine and the findings regarding type, level and position of
      lumbar disc prolapse, any neural canal or foraminal compromise was recorded.
      These imaging findings were then correlated with clinical signs and symptoms. Chi
      square test was used to find out p-value for correlation between clinical
      features and Magnetic resonance imaging findings using SPSS 17.0. RESULTS: This
      study included 57 patients, with mean age 36.8 years. Of them 41(71.9%) patients
      had radicular leg pain along specific dermatome. Magnetic resonance imaging
      showed 104 lumbar disc prolapselevel. Disc prolapse at L4-L5 and L5-S1 level
      constituted 85.5%.Magnetic resonance imaging findings of neural foramina
      compromise and nerve root compression were fairly correlated withclinical
      findings of radicular pain and neurological deficit. CONCLUSIONS: Clinical
      features and Magnetic resonance imaging findings of lumbar discprolasehad
      faircorrelation, but all imaging abnormalities do not have a clinical
      significance.

PMID- 27885289
TI  - Assessment of Knee Joint Injuries with Low Field Strength Magnetic Resonance
      Imaging.
AB  - BACKGROUND: Magnetic Resonance Imaging is an appropriate screening tool before
      therapeutic arthroscopy, making diagnostic arthroscopy unnecessary in most
      patients. This study aims to evaluate the MRI findings in knee injuries and
      diagnostic value of low Strength MRI for assessing Meniscal and cruciate ligament
      tear. METHODS: A cross sectional study was conducted on patients undergoing
      "Magnetic Resonance Imaging of the Knee" for injuries of the knee and excluded
      patients undergoing MRI for other causes, poor diagnostic quality MRI and post
      operative MRI. All patients were interviewed for mechanism of injury and followed
      up for arthroscopic findings. Statistical analysis was doe using IBM SPSS 20.0.
      RESULTS: A total of 81 MRIs was included in the study. Arthroscopic finding of
      only 32 patients could be followed up. Anterior cruciate ligament (ACL) tear was
      the most common internal ligament tear accounting for 34(42%) of cases followed
      by medial meniscus tear in 33(40.7%). Twisting 14( 42.4%)was the most common
      mechanism involved in medial meniscus tear while combined mechanism of injury was
      most common mechanism for ACL tear 16( 47.05%). The sensitivity of MRI for
      diagnosis of ACL tear and medial meniscus tear was 96.3% and 94.7% respectively.
      Specificity for ACL tear was however only 80% and that for medial meniscus tear
      was 100%. CONCLUSIONS: The diagnostic value of MRI for diagnosing internal
      derangement of knee was high even with a low Tesla (0.3 T) MRI thus emphasizing
      the role of MRI as a non-invasive alternative to diagnostic arthroscopy.

PMID- 27885290
TI  - Effectiveness of Spinal Anaesthesia versus General Anaesthesia for Open
      Cholecystectomy.
AB  - BACKGROUND: Cholecystectomy is performed either as an open or a laparascopic
      route. Despite of a number of peri-operative and post-operative benefits of
      laparascopic cholecystectomy, the traditional and invasive open cholecystectomy
      is still in frequent practice for various reasons. Though general anaesthesia is
      regarded as the gold standard anaesthetic technique, alternatives to it such as
      spinal anaesthesia, with its advantages, outweighs general anaesthesia. Spinal
      anaesthesia, therefore, could be a safe and effective anaesthetic procedure over
      general anaesthesia for open cholecystectomy. METHODS: 120 patients with
      uncomplicated symptomatic gallstone disease undergoing open cholecystectomy and
      complying with ASA I or II physical status, aged between 18 and 70 years of
      either sex and BMI <= 30 kg/m2 were enrolled for the study. They were randomly
      categorized into SA group (received spinal anaesthesia) and GA group (received
      general anaesthesia), each group containing 60 patients. Intra-operative events
      and post-operative events were observed up to 48 hours post-surgery and compared
      between the groups. Data is in percentage and mean with standard deviation and
      median. Statistical analysis was done using independent t-test, chi-square test,
      relative risks and ANOVA. RESULTS: Spinal anaesthesia is safe and effective in
      pain management post open cholecystectomy. The median pain-free intervalin SA
      group was 8hours as compared to 1 hour in GA group. The average mean pain score
      was also significantly less in SA group than in GA group at all intervals of time
      observed. Majority (90%) in SA groups were managed with intramuscular
      diclofenacsodium whereas majority in GA group were managed with intramuscular
      pethedine. Intra-operatively, SA group had more cases of haemodynamic instability
      than GA group, which were easily managed in both the groups. The differences in
      the incidence of post-operative nausea and vomiting and the days of hospital stay
      between the groups were not significant. CONCLUSIONS: Spinal anaesthesia is safe
      and more effective than general anaesthesia for uncomplicated open
      cholecystectomy in terms of peri-operative events and, in reducing post-operative
      pain, as well as in terms of surgeon's satisfaction as well.

PMID- 27885283
TI  - Induced protein degradation: an emerging drug discovery paradigm.
AB  - Small-molecule drug discovery has traditionally focused on occupancy of a binding
      site that directly affects protein function, and this approach typically
      precludes targeting proteins that lack such amenable sites. Furthermore, high
      systemic drug exposures may be needed to maintain sufficient target inhibition in
      vivo, increasing the risk of undesirable off-target effects. Induced protein
      degradation is an alternative approach that is event-driven: upon drug binding,
      the target protein is tagged for elimination. Emerging technologies based on
      proteolysis-targeting chimaeras (PROTACs) that exploit cellular quality control
      machinery to selectively degrade target proteins are attracting considerable
      attention in the pharmaceutical industry owing to the advantages they could offer
      over traditional small-molecule strategies. These advantages include the
      potential to reduce systemic drug exposure, the ability to counteract increased
      target protein expression that often accompanies inhibition of protein function
      and the potential ability to target proteins that are not currently
      therapeutically tractable, such as transcription factors, scaffolding and
      regulatory proteins.

PMID- 27885291
TI  - Factors Determining Availability, Utilization and Retention of Child Health Card
      in Western Nepal.
AB  - BACKGROUND: The immunization card is revised with addition of general information
      about child health and is later called as child health card. This card is a tool
      used by Health Management Information System in Nepal. It is important for
      tracking the records of immunization. Aim is to identify the factors determining
      the availability, utilization and retention of the child health card in Western
      Nepal. METHODS: A cross sectional study was conducted among mothers having
      children < 24 months old from Gorkha (Western Hill) and Nawalparasi (Western
      Terai) districts. The sample size for the study was 600 and systematic random
      sampling was used to select the mothers having less than 24 months old children.
      Data entry and analysis was done by using SPSS. Qualitative data was analyzed by
      making matrix. RESULTS: The average age of respondents was 24 years. The majority
      of respondents have gained higher level education. Retention of the card was
      found to be 82.2%. 90.3% retention was seen among 0-12 months children age group
      whereas it was 74 % among12 to 24 months age group. The reasons for less
      retention were torn by the child/played by child (54.6%) followed by lack of
      proper place,unaware about importance and poor quality of card.The new child
      health cards were insufficient, compelling use of both new and old cards which
      created problem in consistency. Regarding utilization of child health card, it
      was found to be used for birth registration and for further studies in abroad.
      CONCLUSIONS: The areas of utilization of child health card should be broadened so
      that the retention of card can be increased. The main reasons for less retention
      of the card are torn by children and lack of the proper place.

PMID- 27885292
TI  - An Assessment of Diabetic Retinopathy and Diabetes Management System in Nepal.
AB  - BACKGROUND: Visual damage due to diabetic retinopathy is a major concern which
      can be reduced through appropriate coordination and cooperation between the
      diabetes management services and diabetic retinopathy services. The study
      assessed the existence, availability and accessibility of health care services
      for diabetes mellitus and diabetic retinopathy in Nepal. METHODS: The study was
      carried out from 1 April to 24 June 2015. The tool for assessment of diabetic
      retinopathy and diabetes management systems developed by the World Health
      Organization was used for the assessment of major stakeholders like
      endocrinologists, ophthalmologists, ophthalmic assistants, nurses involved in
      diabetes care, patients and human resources from Ministry of Health and
      Population and international non-governmental organizations dealing with eye care
      services in Nepal. RESULTS: Thirty-seven key stakeholders were selected for the
      study. Six out of fifteen ophthalmologists were unaware about the prioritization
      of diabetes as national health concern. The main function of diabetes association
      included patient education and awareness 18(48.6%), clinician education and
      awareness 16(43.2%). Thirteen professionals (35.1%) said that the patients were
      not found to be aware about diabetic patients' organizations. The information to
      community is provided occasionally and only through national-level media. All
      forms of diabetes care were funded out-of-pocket by the patients themselves.
      CONCLUSIONS: Coordination should be strengthened for an effective and holistic
      management of diabetes mellitus making diabetes care and diabetic retinopathy
      services more accessible. Diabetes mellitus and its complications are becoming a
      public health threat in Nepal.

PMID- 27885294
TI  - Infant and Young Child Feeding Practices among Mothers at Chapagaun VDC.
AB  - BACKGROUND: Since childhood under nutrition and mortality are high in Nepal,
      promotion of infant and young child feeding practices among children is most
      critical intervention,which contributes to improved nutrition, health and
      development of children ultimately having impact on child survival. The objective
      of the study was to identify infant and young child feeding practices. METHODS: A
      descriptive cross-sectional study was carried out among mothers visiting
      Chapagaun Primary Health Care and Resource Centre (PHCRC) with child aged 6-23
      months between January1-14, 2016. Interview of 62 respondents was done by using
      structured questionnaire. The obtained data was analyzed by using Statistical
      Package for Social Sciences (SPSS) version 20 and Chi square test was performed.
      RESULTS: Majority (72.6%) initiated breastfeeding within 1 hour of delivery and
      gave colostrum as the first feed to the child. The rate of exclusive
      breastfeeding was 61.3%. Some of the children were initiated complementary
      feeding after 6 months, while 58% mothers practiced complementary feeding after
      the recommended age and 38.6% even before the recommended age. One fifth of the
      children received dietary diverse meal. Only 12.9% received complementary food
      with recommended frequency, 40.3% with appropriate consistency and 12.9% with
      adequate amount. Statistically there was significant association of practice with
      age of mother and mode of delivery. CONCLUSIONS: The practice of breastfeeding
      was good while complementary feeding practices were poor. The feeding practices
      were found to be sub-optimal. The findings from the study highlight the
      importance of education at immunization clinic in order to improve the practices.

PMID- 27885293
TI  - Prevalence of Extended Spectrum Beta-Lactamase Producing Klebsiella Pneumoniae
      Isolated From Urinary Tract Infected Patients.
AB  - BACKGROUND: Klebsiella pneumoniae, one of the bacterial agents associated with
      urinary tract infection has been often implicated as a major extended spectrum
      beta-lactamase (ESBL) producer in last few decades. This study was designed to
      assess the prevalence of ESBL producing Klebsiella pneumoniae in urinary isolates
      at a tertiary care hospital in Kathmandu, Nepal, from July to December 2014.
      METHODS: One thousand nine hundred eighty six mid-stream urine specimens were
      collected aseptically from the clinically suspected patients of urinary tract
      infections attending Capital Hospital and Research Center, Kathmandu. The samples
      were processed following standard guidelines as recommended by American Society
      for Microbiology (ASM) and the isolates including Klebsiella spp. were identified
      using the specific biochemical and sugar fermentation tests recommended by ASM.
      Antibiotic sensitivity testing was done by modified Kirby-Bauer disk diffusion
      method and interpreted following Clinical and Laboratory Standards Institute
      (CLSI) guidelines. Klebsiella pneumoniae isolates showing resistance upon initial
      screening with ceftriaxone (30 MUg) disc were then confirmed for ESBL production
      by phenotypic confirmatory disc diffusion test (PCDDT) using ceftazidime (30 ug)
      and ceftazidime + clavulanic acid (30 ug + 10ug) and cefotaxime (30 ug) and
      cefotaxime + clavulanic acid (30 ug +10ug) disc as per CLSI guidelines. RESULTS:
      Out of a total 1986 specimens investigated, Escherichia coli was isolated in 309
      (83.9%) and Klebsiella pneumoniae in 38 (10.3%) cases. Initial screening with
      ceftriaxone disc revealed 18 isolates of Klebsiella pneumoniae to be resistant.
      Further testing by PCDDT method confirmed 7 (18.4%) Klebsiella pneumoniae
      isolates to be ESBL producers. CONCLUSIONS: Compared to some earlier studies done
      in Nepal, higher prevalence of ESBL-producing Klebsiella pneumoniae was observed
      warranting a national surveillance for routine monitoring of ESBL producing
      Klebsiella pneumoniae isolates.

PMID- 27885295
TI  - Scrub Typhus: An Emerging Neglected Tropical Disease in Nepal.
AB  - BACKGROUND: Scrub typhus is a neglected tropical disease and is under reported
      from Nepal. The objective of this study was to investigate the sero-epidemiology
      of scrub typhus in patients suffering from acute febrile illness. METHODS: A
      total of 434 specimens collected from July to November 2015 at National Public
      Health Laboratory (NPHL) were investigated for detection of immunoglobulin M
      (IgM) antibody to Orientiatsutsugamushi.The Scrub Typhus Detect TM kit (InBios,
      USA) was used to detect the antibodies to O.tsutsugamushi in human serum.
      Randomly selected 10% positive specimens were used for confirmation by dot-
      enzyme-linked immunosorbent assay and indirect immunofluorescence assay. RESULTS:
      Of the total, 175 (40.3%) were positive for IgM antibodies to O. tsutsugamushi.
      Positive results of scrub typhus were highest among female in 11-20 year followed
      by males in 41-50 years age group. The IgM antibodies to O. tsutusugamushi were
      positive in specimens of various geographical regions including 30 districts of
      Nepal. Positive cases were found in various ecological regions of Nepal.
      CONCLUSIONS: Scrub typhus is one of the neglected tropical diseases in Nepal.
      Patients with acute febrile illness should be investigated for scrub typhus with
      high priority. There is an urgent need of reliable and affordable diagnostic
      tests at all level of health facilities of Nepal. Surveillance and public health
      awareness about the disease transmission and preventive measures needs to be
      initiated.

PMID- 27885296
TI  - Outcome of Twin Deliveries at a Tertiary Care Centre of Eastern Nepal.
AB  - BACKGROUND: Twins, compared to singletons, have higher perinatal mortality and
      morbidity. The aim of this study was to describe the twinning rate,
      epidemiological variables and hospital outcome of twin deliveries and to find out
      ways of better management of twins in our part. METHODS: A retrospective
      evaluation of the outcome of 92 twin pregnancies during one year study period
      (1st January 2014 to 31st December 2014) was conducted at BPKIHS. Twins delivered
      within the institution were included but cases less than 28 weeks gestation were
      excluded. Maternal and neonatal data were retrieved and analysed. RESULTS: The
      twinning rate was 9.2/1000 (92/10,031). The mean birth weight was 1636.30 +/
      339.21 grams and mean gestational age 34.31+/-2.67 weeks(28 - 40 weeks). One
      hundred eighty-two babies (98.9%) were low birth weight (LBW) while 32.1% were
      small for gestational age (SGA). There was mild, moderate and severe growth
      discordance in 63 (68.5%)22 (23.9%)and 7 (7.6%) respectively. Three (3.26%) of 92
      pairs had twin-to-twin transfusion syndrome. The hospital mortality rate was
      10.87% (20/184) and 69 (37.5%) babies had complications. The clinical causes of
      death were hyaline membrane disease in 7 (3.3%), severe birth asphyxia in 5
      (2.7%), congenital malformations in 3(1.6%) and sepsis in 3 (1.6%) babies.
      CONCLUSIONS: Twin deliveries are common in this hospital and have poor hospital
      outcome with more complications and mortality. Hence there is a need for further
      studies with long term follow-ups to plan for better management of twins in our
      part.

PMID- 27885297
TI  - Mimicker of Renal Colic: Mesenteric Panniculitis.
AB  - A Mesenteric panniculitis is an uncommon disorder with unknown etiology. It may
      cause nonspesific abdominal or systemic symptoms. Radiological modalitis
      especially computed tomography are very helpful to make a diagnosis. Hence, the
      radiologist should be familiar with its tomographic findings to avoid further
      examinations and unnecessary surgery. We report computed tomography findings of
      mesenteric panniculitis in an adult patient with renal colic.

PMID- 27885298
TI  - Klippel-Trenaunay Syndrome: A Case Report.
AB  - Klippel-Trenaunaysyndrome(KTS) is a rare congenital condition usually presenting
      with port wine stains, excessive growth of bones and soft tissue and varicose
      veins which most commonly occurs in the legs, but it also may affect the arms,
      face, head, or internal organs. We report a case of term male neonate with
      clinical findings of Port-wine stain, multiple cystic swellings with
      ultrasonographic findings suggestive of vascular malformations and limb
      abnormalities in the form ofsoft tissue hypertrophy of right upper limb,
      polydactyly of right hand and syndactyly of left hand consistent withKlippel
      Trenaunay syndrome.

PMID- 27885299
TI  - Influence of internal geometry on magnetization reversal in asymmetric permalloy
      rings.
AB  - We report the magnetization reversal behavior of microstructured Ni80Fe20 rings
      using magneto-optic indicator film imaging and magnetometry. While the reversal
      behavior of rings with a symmetric (circular) interior hole agrees with
      micromagnetic simulations of an onion -> vortex -> onion transition, we
      experimentally demonstrate that rings possessing an elliptical hole with an
      aspect ratio of 2 exhibit complex reversal behavior comprising incoherent domain
      propagation in the rings. Magneto optic images reveal metastable magnetic
      configurations that illustrate this incoherent behavior. These results have
      important implications for understanding the reversal behavior of asymmetric
      ferromagnetic rings.

PMID- 27885300
TI  - Rebooting the Franchise: The 2015 International Symposium on GPC/SEC and Related
      Techniques.

PMID- 27885301
TI  - Prevalence and Mortality of Melanoma in Oklahoma Among Racial Groups, 2000-2008.
AB  - INTRODUCTION: This study assessed the period prevalence (2000-2008) and mortality
      rates of melanoma, in Oklahoma, among different racial/ethnic strata. METHODS: We
      analyzed incident cases of melanoma from 2000-2008 from the Oklahoma Central
      Cancer Registry and determined disease duration using Kaplan-Meier survival
      analysis to calculate period prevalence of melanoma in Oklahoma. Using a series
      of Chi-Square tests, we compared period prevalence and mortality rates among the
      racial groups and compared mortality between Oklahoma and the US. RESULTS: White
      non-Hispanics in Oklahoma have the highest period prevalence (p<0.0001) among the
      racial strata. American Indian or Alaska Native (AI/AN) individuals have the
      second highest period prevalence in Oklahoma (p<0.0001). Furthermore, white non
      Hispanics (p<0.0001) and AI/AN individuals (p=0.0003) in Oklahoma had higher
      mortality rates compared to the US. CONCLUSIONS: There are disparities in the
      prevalence and mortality of melanoma among the AI/AN population in Oklahoma, and
      prevention and education programs should focus on this population.

PMID- 27885302
TI  - Cancers of the Thyroid: Overview and Statistics in the United States and
      Oklahoma.
AB  - Recent studies have shown an apparent increase in thyroid cancer in the United
      States. Whether is due to an actual increase or increased screening is disputed.
      We analyzed thyroid cancer incidence and mortality across age and racial groups
      in Oklahoma (using data from the Oklahoma Central Cancer Registry) against
      Surveillance, Epidemiology, and End Results (SEER) program national data - using
      SEER*Stat software for mortality. In the US and Oklahoma, females had a higher
      AAIR compared to males, but it was lower in Oklahoma than in the US (Females: US
      15.5 per 100,000, OK 10.9 per 100,000; Males: US 5.4 per 100,000, OK 3.8 per
      100,000). Overall, five-year relative survival was lower, yet still high, for
      Oklahoma than in the US (92.1% v. 97.1%). Survival by stage was lower in Oklahoma
      compared to the United States for localized (97.8% v. 99.8%), regional (92.0% v.
      97.0%), and distant (36.6% v. 55.3%) stage cancers.

PMID- 27885303
TI  - Oral Cavity and Oropharyngeal Cancer: Changing Trends in Incidence in the United
      States and Oklahoma.
AB  - Oral cavity cancer (OC) has steadily decreased in the United States (US) since
      1973 whereas oropharyngeal cancer (OP) has increased. We analyzed OC and OP cases
      from the Oklahoma Central Cancer Registry and Surveillance, Epidemiology, and End
      Results program comparing those diagnosed from 1997-1999 to those diagnosed from
      2010-2012. We compared the incidence of OC and OP cases between Oklahoma and the
      US and by demographic factors. We observed an increase in OP cases, but no change
      in OC cases in both the US and in Oklahoma, and observed some differences between
      Oklahoma and the US by race, gender, and age group. A possible explanation for
      the increasing incidence of OP cancers may be the increasing prevalence of HPV.
      This study highlighted the differences in temporal trends of OC and OP cancers
      and the importance of changing risk factors for these cancers.

PMID- 27885304
TI  - Trends in Lung and Bronchus, Prostate, Female Breast, and Colon and Rectum
      Cancers Incidence and Mortality in Oklahoma and the United States from 1999 to
      2012.
AB  - BACKGROUND: Cancer is the second-leading cause of death in the United States (US)
      and Oklahoma ranks near the top with the highest rates of mortality from cancer.
      The top four major sites of cancer were prostate, female breast, lung and
      bronchus, and colon and rectum. METHODS: Joinpoint software was used to examine
      the incidence and mortality for the four cancers over time from 1999-2012 for
      both the US and Oklahoma. RESULTS: Incidence and mortality rates declined from
      1999-2012 for the four cancer sites. The average annual, age-adjusted incidence
      rate was higher in the US than Oklahoma for prostate cancer, but higher in
      Oklahoma for female breast, lung and bronchus, and colon and rectum cancer sites.
      CONCLUSIONS: Over the course of 14 years from 1999-2012, the age-adjusted
      incidence and mortality rates of prostate cancer, female breast cancer, lung and
      bronchus cancer, and colon and rectum cancer decreased over time nationally and
      in Oklahoma.

PMID- 27885305
TI  - Racial, Ethnic, and Age Differences in the Incidence and Survival of Childhood
      Cancer in Oklahoma, 1997-2012.
AB  - While cancer is relatively rare in children under 20, it is the leading cause of
      disease-related death among children aged 5 to 14 years. We aimed to describe the
      incidence and survival of childhood cancer in Oklahoma from 1997-2012. We
      calculated age-adjusted incidence rates and five-year observed survival by cancer
      type using Oklahoma Central Cancer Registry and Surveillance, Epidemiology, and
      End Results program data among children diagnosed with cancer under the age of 20
      from 1997-2012. The average annual age-adjusted incidence rate of childhood
      cancer was 168.9 per million for the US and 171.7 per million for Oklahoma.
      Overall, Oklahoma had lower survival from childhood cancer compared to the US
      (77.0% v. 80.6%). In recent years, research has been conducted on the
      epidemiology of childhood cancer. Little research has been done, however, on the
      incidence or survival of childhood cancer at state levels and none focused
      exclusively on Oklahoma.

PMID- 27885306
TI  - Impact of a National Cancer Prevention and Treatment Program on the Prevalence of
      Late-Stage Breast Cancer Diagnoses in Oklahoma.
AB  - In 2000, Congress passed the Breast and Cervical Cancer Prevention and Treatment
      Act (BCCPTA) to provide coverage through Medicaid to women who screened positive
      for breast and cervical cancer. We aimed to determine if late-stage breast cancer
      prevalence decreased among Oklahoma women after passage of BCCPTA. Data were
      obtained from the Oklahoma Central Cancer Registry during 2000-2011. We estimated
      prevalence proportion ratios (PPR) using modified Poisson regression between the
      proportion of women with late-stage breast cancer and timing of diagnosis related
      to BCCPTA. Among uninsured women, the probability of being diagnosed with late
      stage cancer after enactment of the BCCPTA was 0.80 (95% CI: 0.67, 0.96) times
      the probability before enactment. This was significant among uninsured women
      living in metro counties (PPR: 0.74, 95% CI: 0.61, 0.90) but not in non-metro
      counties (PPR: 1.05, 95% CI: 0.71, 1.56). These findings may be similar to other
      rural states with large uninsured populations.

PMID- 27885307
TI  - Epidemiology of Testicular Cancer in Oklahoma and the United States.
AB  - Testicular cancer is a rare cause of morbidity and mortality in the US. Marked
      disparities in the development of this cancer exist, with testicular cancer being
      more common in Caucasian men and men of higher socioeconomic status. The
      incidence of testicular cancer is increasing worldwide, and the reasons for this
      have not been well documented. It has been proposed that this increase may be due
      to highly prevalent environmental factors, or from exposure to polychlorinated
      biphenyls, polyvinyl chloride, cigarette smoking, and tetrahydrocannabinol (THC).
      For our analysis, data were obtained from the Oklahoma Central Cancer Registry
      and the Surveillance, Epidemiology and End Results program. Age-adjusted
      incidence rates and five-year relative survival were calculated for Oklahoma and
      for the US. Overall, incidence was lower in Oklahoma than the US, but no
      differences were observed between the US and Oklahoma regarding survival by year
      of diagnosis, race, age, and stage.

PMID- 27885310
TI  - Concurrent generation of multivariate mixed data with variables of dissimilar
      types.
AB  - Data sets originating from wide range of research studies are composed of
      multiple variables that are correlated and of dissimilar types, primarily of
      count, binary/ordinal and continuous attributes. The present paper builds on the
      previous works on multivariate data generation and develops a framework for
      generating multivariate mixed data with a pre-specified correlation matrix. The
      generated data consist of components that are marginally count, binary, ordinal
      and continuous, where the count and continuous variables follow the generalized
      Poisson and normal distributions, respectively. The use of the generalized
      Poisson distribution provides a flexible mechanism which allows under- and over
      dispersed count variables generally encountered in practice. A step-by-step
      algorithm is provided and its performance is evaluated using simulated and real
      data scenarios.

PMID- 27885308
TI  - Pancreatic Cancer: A Survival Analysis Study in Oklahoma.
AB  - BACKGROUND: Pancreatic cancer is among the most deadly cancers. Risk factors
      associated with the disease include age, race, sex, smoking status, and diabetes
      status. METHOD: We conducted a prospective analysis of risk factors and length of
      survival among pancreatic cancer patients living in Oklahoma between 1997 and
      2012 (n=6,291). Kaplan-Meier survival curves were created followed by the log
      rank test to compare difference in the survival time. Cox proportional hazard
      regression models were used to examine the strength of association through the
      estimated hazard ratios. RESULTS: The median survival time of the cohort was
      three months. Significant risk factors for reduced survival times included age,
      stage at diagnosis, and year of diagnosis. CONCLUSION: Results are in agreement
      with previous research findings. There have been small but noteworthy
      improvements in survival times for pancreatic cancer patients in Oklahoma. Length
      of survival during the study period was significantly associated with known risk
      factors such as age and stage of diagnosis.

PMID- 27885309
TI  - Transcranial Direct Current Stimulation Use in the Treatment of Neuropsychiatric
      Disorders: A Brief Review.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive brain
      stimulation technique that has grown in popularity over the past two decades as
      an alternative treatment option for various neuropsychiatric disorders. tDCS
      modulates cortical excitability through the application of a weak direct current
      to the scalp via electrodes placed over cortical regions of interest. It has been
      shown to be a promising and relatively safe treatment tool with few adverse
      events. In this article, we will briefly review the efficacy of tDCS in
      depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder.
      We will also discuss biomarkers of tDCS efficacy in depression, as it is the most
      studied neuropsychiatric disorder using tDCS application. We will then offer
      suggestions for future directions. Although efficacy results show promise, more
      studies with larger samples and longer treatment periods are needed to better
      understand the benefits of using tDCS as an alternative treatment option for
      neuropsychiatric disorders.

PMID- 27885311
TI  - Mediating pathways in the socio-economic gradient of child development: Evidence
      from children 6-42 months in Bogota.
AB  - Research has previously shown a gap of near 0.5 of a standard deviation (SD) in
      cognition and language development between the top and bottom household wealth
      quartile in children aged 6-42 months in a large representative sample of low-
      and middle-income families in Bogota, using the Bayley Scales of Infant and
      Toddler Development. The gaps in fine motor and socio-emotional development were
      about half that size. Developmental deficits increased with age. The current
      study explored the associations amongst child development, household socio
      economic status (SES), and a set of potential mediating variables-parental
      characteristics, child biomedical factors, and the quality of the home
      environment-in this sample. We ran mediation tests to quantify the contribution
      of these variables to the SES gap, and explored the role of age as a moderator.
      Parental education, particularly maternal education, and the quality of the home
      environment mediated the SES gap in all outcomes examined. Height-for-age
      mediated a small amount of the deficit in language scales only. More educated
      mothers provided better home stimulation than less educated mothers and the home
      environment partly mediated the effect of maternal education. These results
      suggested that in interventions aimed at promoting child development, those
      focusing on the quality of the home environment should be effective.

PMID- 27885312
TI  - Implementing Speed and Separation Monitoring in Collaborative Robot Workcells.
AB  - We provide an overview and guidance for the Speed and Separation Monitoring
      methodology as presented in the International Organization of Standardization's
      technical specification 15066 on collaborative robot safety. Such functionality
      is provided by external, intelligent observer systems integrated into a robotic
      workcell. The SSM minimum protective distance function equation is discussed in
      detail, with consideration for the input values, implementation specifications,
      and performance expectations. We provide analytical analyses and test results of
      the current equation, discuss considerations for implementing SSM in human
      occupied environments, and provide directions for technological advancements
      toward standardization.

PMID- 27885313
TI  - Chloride diffusivity in hardened cement paste from microscale analyses and
      accounting for binding effects.
AB  - The diffusion of chloride ions in hardened cement paste (HCP) under steady-state
      conditions and accounting for the highly heterogeneous nature of the material is
      investigated. The HCP microstructures are obtained through segmentation of X-ray
      images of real samples as well as from simulations using the cement hydration
      model CEMHYD3D. Moreover, the physical and chemical interactions between chloride
      ions and HCP phases (binding), along with their effects on the diffusive process,
      are explicitly taken into account. The homogenized diffusivity of the HCP is then
      derived through a least square homogenization technique. Comparisons between
      numerical results and experimental data from the literature are presented.

PMID- 27885314
TI  - In Pursuit of Optimal Cytoreduction in Ovarian Cancer Patients: The Role of
      Surgery and Surgeon.
AB  - The standard of care for women with advanced stage epithelial ovarian cancer
      (EOC) involves surgery followed by adjuvant platinum-based combination
      chemotherapy. One of the goals of surgery is to resect all macroscopic disease.
      In this review we will discuss the justification for an aggressive surgical
      approach, including a discussion of factors limiting its implementation and
      suggestions for providing appropriate surgical intervention for all women with
      EOC.

PMID- 27885315
TI  - Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium
      difficile Infection Among Medicare Beneficiaries.
AB  - BACKGROUND: The management of Clostridium difficile infection (CDI) among
      hospitalized patients is costly, and ongoing payment reform is compelling
      hospitals to reduce its burden. To assess the impact of CDI on mortality,
      hospital costs, healthcare use, and Medicare payments for beneficiaries who were
      discharged with CDI listed as a secondary International Classification of
      Diseases, Ninth Revision, Clinical Modification claim diagnosis. METHODS: Data
      were analyzed from the 2009 to 2010 5% random sample Medicare Standard Analytic
      Files of beneficiary claims. Patients with index hospitalizations with CDI as a
      secondary diagnosis and no previous hospitalization within 30 days were
      identified. Outcomes included inpatient and 30-day mortality, inpatient costs,
      index hospital payments, all-provider payments, net hospital losses, payment to
      cost ratio, length of stay (LOS), and 30-day readmission; outcomes were each risk
      adjusted using propensity score matching and regression modeling techniques.
      RESULTS: A total of 3262 patients with CDI were identified after matching to
      patients without a CDI diagnosis. After risk adjustment, secondary CDI was
      associated with statistically significantly (all P < 0.05) greater inpatient
      mortality (3.1% vs. 1.7%), 30-day mortality (4.1% vs. 2.2%), longer LOS (7.0 days
      vs. 3.8 days), higher rates of 30-day hospital readmissions (14.8% vs. 10.4%),
      and greater hospital costs ($16,184 vs. $13,954) compared with the non-CDI
      cohort. The risk-adjusted payment-to-cost ratio was shown to be lower for
      patients with CDI than those without (0.76 vs. 0.85). CONCLUSIONS: Secondary CDI
      is associated with greater adjusted mortality, costs, LOS, and hospital
      readmissions, while receiving similar hospital reimbursement compared with
      patients without CDI in a Medicare population.

PMID- 27885317
TI  - Poetry and Neuroscience: : An Interdisciplinary Conversation.
AB  - Dialogues and collaborations between scientists and non-scientists are now widely
      understood as important elements of scientific research and public engagement
      with science. In recognition of this, the authors, a neuroscientist and a poet,
      use a dialogical approach to extend questions and ideas first shared during a lab
      based poetry residency. They recorded a conversation and then expanded it into an
      essayistic form, allowing divergent disciplinary understandings and uses of
      experiment, noise, voice and emotion to be articulated, shared and questioned.

PMID- 27885316
TI  - Bartonella Endocarditis and Pauci-Immune Glomerulonephritis: A Case Report and
      Review of the Literature.
AB  - Among culture-negative endocarditis in the United States, Bartonella species are
      the most common cause, with Bartonella henselae and Bartonella quintana
      comprising the majority of cases. Kidney manifestations, particularly
      glomerulonephritis, are common sequelae of infectious endocarditis, with nearly
      half of all Bartonella patients demonstrating renal involvement. Although a pauci
      immune pattern is a frequent finding in infectious endocarditis-associated
      glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti
      neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens
      causing endocarditis and has been previously reported with Bartonella species. In
      addition, ANCA-associated vasculitis can also present with renal and cardiac
      involvement, including noninfectious valvular vegetations and pauci-immune
      glomerulonephritis. Given the overlap in their clinical presentation, it is
      difficult to differentiate between Bartonella endocarditis and ANCA-associated
      vasculitis but imperative to do so to guide management decisions. We present a
      case of ANCA-positive Bartonella endocarditis with associated pauci-immune
      glomerulonephritis that was successfully treated with medical management alone.

PMID- 27885318
TI  - Multiscale Opening of Conjoined Fuzzy Objects: Theory and Applications.
AB  - Theoretical properties of a multi-scale opening (MSO) algorithm for two conjoined
      fuzzy objects are established, and its extension to separating two conjoined
      fuzzy objects with different intensity properties is introduced. Also, its
      applications to artery/vein (A/V) separation in pulmonary CT imaging and carotid
      vessel segmentation in CT angiograms (CTAs) of patients with intracranial
      aneurysms are presented. The new algorithm accounts for distinct intensity
      properties of individual conjoined objects by combining fuzzy distance transform
      (FDT), a morphologic feature, with fuzzy connectivity, a topologic feature. The
      algorithm iteratively opens the two conjoined objects starting at large scales
      and progressing toward finer scales. Results of application of the method in
      separating arteries and veins in a physical cast phantom of a pig lung are
      presented. Accuracy of the algorithm is quantitatively evaluated in terms of
      sensitivity and specificity on patients' CTA data sets and its performance is
      compared with existing methods. Reproducibility of the algorithm is examined in
      terms of volumetric agreement between two users' carotid vessel segmentation
      results. Experimental results using this algorithm on patients' CTA data
      demonstrate a high average accuracy of 96.3% with 95.1% sensitivity and 97.5%
      specificity and a high reproducibility of 94.2% average agreement between
      segmentation results from two mutually independent users. Approximately, twenty
      five to thirty-five user-specified seeds/separators are needed for each CTA data
      through a custom designed graphical interface requiring an average of thirty
      minutes to complete carotid vascular segmentation in a patient's CTA data set.

PMID- 27885319
TI  - Work-Related Psychosocial Factors and Mental Health Problems Associated with
      Musculoskeletal Pain in Nurses: A Cross-Sectional Study.
AB  - Background. Musculoskeletal pain is the most common cause of incapacity among
      nurses. This study aimed to report the prevalence of musculoskeletal pain among
      hospital nurses and to explore the associations of work-related psychosocial
      factors and mental health problems with musculoskeletal pain. Methods. A cross
      sectional survey was carried out among registered nurses at Tartu University
      Hospital during April and May 2011. Binary logistic regression was used to assess
      the associations between dependent and independent variables. Results. Analysis
      was based on 404 nurses (45% of the hospital's nursing population). The overall
      prevalence of MSP was 70% in the past year and 64% in the past month. Lower back
      (57%) and neck (56%) were the body areas most commonly painful in the past year.
      Higher quantitative and emotional demands, work pace, low justice and respect in
      the workplace, influence on work organisation, and role conflicts were
      significantly associated with musculoskeletal pain among nurses (p < 0.05). All
      mental health problems and most strongly somatic stress symptoms were associated
      with musculoskeletal pain. Conclusions. Work-related psychosocial risk factors
      and mental health problems, especially somatic stress symptoms, have an important
      impact on the occurrence of musculoskeletal pain among university hospital
      nurses.

PMID- 27885320
TI  - From by-product to valuable components: Efficient enzymatic conversion of lactose
      in whey using beta-galactosidase from Streptococcus thermophilus.
AB  - beta-Galactosidase from Streptococcus thermophilus was overexpressed in a food
      grade organism, Lactobacillus plantarum WCFS1. Laboratory cultivations yielded
      11,000 U of beta-galactosidase activity per liter of culture corresponding to
      approximately 170 mg of enzyme. Crude cell-free enzyme extracts obtained by cell
      disruption and subsequent removal of cell debris showed high stability and were
      used for conversion of lactose in whey permeate. The enzyme showed high
      transgalactosylation activity. When using an initial concentration of whey
      permeate corresponding to 205 g L-1 lactose, the maximum yield of galacto
      oligosaccharides (GOS) obtained at 50 degrees C reached approximately 50% of
      total sugar at 90% lactose conversion, meaning that efficient valorization of the
      whey lactose was obtained. GOS are of great interest for both human and animal
      nutrition; thus, efficient conversion of lactose in whey into GOS using an
      enzymatic approach will not only decrease the environmental impact of whey
      disposal, but also create additional value.

PMID- 27885321
TI  - Experimental measurement and modelling of reactive species generation in TiO2
      nanoparticle photocatalysis.
AB  - The generation of reactive species in titanium dioxide (TiO2) nanoparticle
      photocatalysis was assessed in a laboratory scale setup, in which P25 Aeroxide
      TiO2 suspensions were photoactivated by means of UV-A radiation. Photogenerated
      holes and hydroxyl radicals were monitored over time by observing their selective
      reaction with probe compounds, iodide and terephthalic acid, respectively. TiO2
      aggregate size and structure were characterized over the reaction time. Reactive
      species quenching was then described by a model, accounting for radiative
      phenomena, TiO2 nanoparticle aggregation and kinetic reactions. The interaction
      between iodide and photogenerated holes was influenced by iodide adsorption on
      TiO2 surface, described by a Langmuir-Hinshelwood mechanism, whose parameters
      were studied as a function of TiO2 concentration and irradiation time. Iodide
      oxidation was effectively simulated by modelling the reaction volume as a
      completely stirred two-dimensional domain, in which irradiation phenomena were
      described by a two-flux model and the steady state for reactive species was
      assumed. The kinetic parameters for iodide adsorption and oxidation were
      estimated and successfully validated in a different experimental setup. The same
      model was adapted to describe the oxidation of terephthalic acid by hydroxyl
      radicals. The kinetic parameters for terephthalic acid oxidation were estimated
      and validated, while the issues in investigating the interaction mechanisms among
      the involved species have been discussed. The sensitivity of operating parameters
      on model response was assessed and the most relevant parameters were highlighted.

PMID- 27885323
TI  - Contested Issues of Efficacy and Safety between Transnational Formulation Regimes
      of Tibetan Medicines in China and Europe.
AB  - Tibetan medicines are key material objects for medical treatment and have become
      part of a global trend of 'pharmaceuticalisation', playing increasingly important
      political and socio-economic roles in an 'alternative modernity'. As I argue in
      this paper, they also have become key 'sites of contestation' between different
      epistemic values and styles of practice related to efficacy and safety that are
      reproduced in and through specific formulation regimes. Based on my multisited
      ethnography of production, prescription, and use practices of Tibetan medicines
      in China and Europe, this paper conceptualises three distinct formulation
      regimes, offering a heuristic model for transnational comparison-a classical, an
      industrialised or reformulated, and a polyherbal regime. The first two are the
      major orientations while the polyherbal is a conjoint hybrid with either the
      classical or the industrialised formulation regime. Globalised national drug
      safety regulations legalise and confer legitimacy to industrialised Tibetan
      formulas that follow biomedically defined efficacy, safety, and disease
      categories, while classical formulas produced by private physicians or small
      scale cottage pharmacies are increasingly marginalised as producing 'unsafe' and
      at times illegal medicines, and need to find new ways for adapting and
      circulating their formulas.

PMID- 27885324
TI  - Clinical Outcome of a Novel Anti-CD6 Biologic Itolizumab in Patients of Psoriasis
      with Comorbid Conditions.
AB  - Psoriasis is a common, chronic, immune mediated, inflammatory disease of skin
      characterized by red patches enclosed with white scales and affects 2-3% of
      people in the world. Topical therapy, phototherapy, and systemic therapy were
      employed for management of disease from many last decades. However, long term
      uses of these agents are associated with unwanted effects and toxicities.
      Recently, Itolizumab has been developed as world's first anti-CD6 humanized
      monoclonal IgG1 antibody for the management of moderate-to-severe chronic plaque
      psoriasis in India. Here we are presenting the response indicated by Itolizumab
      in 7 Indian patients having moderate-to-severe psoriasis with severe
      comorbidities and who were intolerant/nonresponding to conventional therapies.

PMID- 27885322
TI  - Nedley Depression Hit Hypothesis: Identifying Depression and Its Causes.
AB  - Depression is often diagnosed using the Diagnostic and Statistical Manual of
      Mental Disorders Fifth Edition (DSM-5) criteria. We propose how certain lifestyle
      choices and non-modifiable factors can predict the development of depression. We
      identified 10 cause categories (hits or "blows" to the brain) and theorize that
      four or more active hits could trigger a depression episode. Methods. A sample of
      4271 participants from our community-based program (70% female; ages 17-94 years)
      was assessed at baseline and at the eighth week of the program using a custom
      test. Ten cause categories were examined as predictors of depression are (1)
      Genetic, (2)Developmental, (3)Lifestyle, (4)Circadian Rhythm, (5)Addiction,
      (6)Nutrition, (7)Toxic, (8)Social/Complicated Grief, (9)Medical Condition, and
      (10)Frontal Lobe. Results. The relationship between the DSM-5 score and a person
      having four hits categories in the first program week showed a sensitivity of
      89.98 % (95% CI: 89.20 % - 90.73%), specificity 48.84% (CI 45.94-51.75) and
      Matthew Correlation Coefficient (MCC) .41 . For the eight-week test, the results
      showed a sensitivity 83.6% (CI 81.9-85.5), specificity 53.7% (CI 51.7-55.6) and
      MCC .38. Overall, the hits that improved the most from baseline after the eighth
      week were: Nutrition (47%), Frontal lobe (36%), Addiction (24%), Circadian rhythm
      (24%), Lifestyle (20%), Social (12%) and Medical (10%). Conclusions. The Nedley
      four-hit hypothesis seems to predict a depressive episode and correlates well
      with the DSM-5 criteria with good sensitivity and MCC but less specificity.
      Identifying these factors and applying lifestyle therapies could play an
      important role in the treatment of depressed individuals.

PMID- 27885325
TI  - Current Role of Minimally Invasive Radical Cholecystectomy for Gallbladder
      Cancer.
AB  - Background. For Tis and T1a gallbladder cancer (GbC), laparoscopic
      cholecystectomy can provide similar survival outcomes compared to open
      cholecystectomy. However, for patients affected by resectable T1b or more
      advanced GbC, open approach radical cholecystectomy (RC), consisting in
      gallbladder liver bed resection or segment 4b-5 bisegmentectomy, with
      locoregional lymphadenectomy, is considered the gold standard while minimally
      invasive RC (MiRC) is skeptically considered. Aim. To analyze current literature
      on perioperative and oncologic outcomes of MiRC for patients affected by GbC.
      Methods. A Medline review of published articles until June 2016 concerning MiRC
      for GbC was performed. Results. Data relevant for this review were presented in
      13 articles, including 152 patients undergoing an attempt of MiRC for GbC. No
      randomized clinical trial was found. The approach was laparoscopic in 147
      patients and robotic in five. Conversion was required in 15 (10%) patients.
      Postoperative complications rate was 10% with no mortality. Long-term survival
      outcomes were reported by 11 studies, two of them showing similar oncologic
      results when comparing MiRC with matched open RC. Conclusions. Although
      randomized clinical trials are still lacking and only descriptive studies
      reporting on limited number of patients are available, current literature seems
      suggesting that when performed at highly specialized centers, MiRC for GbC is
      safe and feasible and has oncologic outcomes comparable to open RC.

PMID- 27885326
TI  - Review of Clinical Studies of the Treatment of Ulcerative Colitis Using
      Acupuncture and Moxibustion.
AB  - Background. Clinical studies suggest that acupuncture and moxibustion therapy in
      ulcerative colitis (UC) can regulate bowel inflammation, and these treatments
      have the advantages of low rates of adverse reactions and recurrence as well as
      good long-term efficacy. We reviewed the current status of clinical studies of
      the treatment. Methods. Randomized controlled trials (RCTs) using the therapy as
      the major intervention for treating UC were included from 1995 to 2015. The
      extracted data mainly included diagnostic standards, treatment methods, selection
      of acupoints, treatment times and courses, and efficacy determination criteria.
      Results. The use of diagnostic standards and efficacy criteria lacked unification
      and standardization. There were two main groups: acupuncture and moxibustion
      therapy combined with drug treatment and the use of all types of acupuncture and
      moxibustion therapy alone or in combination. The acupoint compositions included
      distal-proximal point combinations, back-shu point and front-mu point
      combinations, and acupuncture through meridians. The treatment courses in all the
      clinical trials had large variations. Conclusion. The treatment of UC in the
      examined articles was mainly based on the classical theory. However, many links
      of the clinical regimen design were still lacking, which affected the
      repeatability of the clinical studies and the accuracy of the clinical
      conclusions.

PMID- 27885327
TI  - Surgical Removal of an Extrauterine Device Migrating to Appendix.
AB  - Intrauterine devices (IUDs) remain highly effective reversible family planning
      methods in developing countries. We aimed to report one of the complications of
      extrauterine and intrauterine devices. A 44-year-old woman was admitted to our
      hospital with mislocated intrauterine device and abnormal uterine bleeding.
      Extrauterine IUD device was proven by ultrasound and X-ray. She had normal blood
      test count with a negative pregnancy test. There are several cases of
      complications with intrauterine devices, but this is the first case report about
      an extrauterine IUD embedded by inflame enlarged appendix presenting with
      abnormal uterine bleeding. Although intrauterine devices are a common safe method
      for contraception, there is no risk-free insertion even with advanced
      ultrasounds. A regular self-examination should be taught to the patients and
      ultrasonography should be performed in the follow-up of the patients especially
      for inserted devices during lactation period. Extrauterine IUDs can be
      successfully removed by laparotomy.

PMID- 27885328
TI  - Preparative Purification of Bioactive Compounds from Flos Chrysanthemi Indici and
      Evaluation of Its Antiosteoporosis Effect.
AB  - To understand the material basis and underlying molecular machinery of
      antiosteoporosis activity of the Flos Chrysanthemi Indici (FCI), the consequences
      of ethanol extract on the bone loss in mice induced due to ovariectomy (OVX) was
      evaluated. Also, the antiosteoporosis fraction obtained from the FCI ethanol
      extract was isolated and purified using a preparative high-speed countercurrent
      chromatography (HSCCC). The in vitro impact of the compounds was investigated on
      osteoblast proliferation and differentiation. The results revealed that ethyl
      acetate fraction with robust in vivo antiosteoporosis activity was obtained. The
      important compounds purified by HSCCC using gradient elution system included
      acacetin, apigenin, luteolin, and linarin. The four compounds enhanced the
      differentiation and proliferation of osteoblasts in MC3T3-E1 cells. They also
      augmented the mRNA levels of runt-related transcription factor 2 (Runx2),
      osteocalcin (OCN), osteopontin (OPN), and type I collagen (COL I). The AKT
      signaling pathway was also activated in MC3T3-E1 cells by the four compounds. The
      present study demonstrated that the antiosteoporosis effects of FCI did not
      depend on a single component, and HSCCC efficiently isolated and purified the
      antiosteoporosis bioactive compounds from FCI.

PMID- 27885330
TI  - Formulation of Propolis Phenolic Acids Containing Microemulsions and Their
      Biopharmaceutical Characterization.
AB  - Microemulsions (MEs) were formulated using PEG-8 caprylic/capric glycerides and
      ethanolic propolis extracts. Characterization of MEs was performed by determining
      mean droplet size, polydispersity index, stability under varying external
      factors, and formulation effect on delivery of phenolic compounds into the skin
      ex vivo. Essential oils were included into the formulations of MEs and their
      influence on physical characteristics of the nanostructured systems as well as
      penetration into epidermis and dermis were evaluated. The droplet size, their
      distribution, and stability of the formulated MEs were not affected. Presence of
      essential oils in the formulation increased penetration of phenolic compounds in
      general, but only the amount of ferulic acid increased significantly. Mean
      droplet size increased with increase of oily phase amount, suggesting that
      phenolic compounds and components of essential oils were not modifying the
      formation of the interphase film composition and/or structure. Phenolic compounds
      were predominantly located in the lipid phase of the MEs thus minimizing their
      availability at the surface of the skin.

PMID- 27885329
TI  - Physical-Performance Outcomes and Biomechanical Correlates from the 32-Week Yoga
      Empowers Seniors Study.
AB  - Background. Yoga Empowers Seniors Study (YESS) quantified physical demands
      associated with yoga performance using biomechanical methods. This study
      evaluated the efficacy of the program on physical function outcomes. Methods.
      Twenty community-dwelling older adults aged 70.7 +/- 3.8 years attended biweekly
      60-minute Hatha yoga classes for 32 weeks. Four domains of the physical
      measurements including (1) functional performance, (2) flexibility, (3) muscle
      strength, and (4) balance were taken at the baseline, 16-week and 32-week time
      points. Repeated-measures ANOVA omnibus tests and Tukey's post hoc tests were
      employed to examine the differences in each outcome variable across the 3 time
      points. Results. Improved timed chair stands (p < 0.01), 8-foot up and go (p <
      0.05), 2-min step test (p < 0.05), and vertical reach (p = 0.05) performance were
      evident. Isometric knee flexor strength (p < 0.05) and repetitions of the heel
      rise test (p < 0.001) also increased following the 32-week intervention. Both
      flexibility and balance performance remained unchanged. Conclusions. Significant
      improvements in physical function and muscle-specific lower-extremity strength
      occur with the regular practice of a modified Hatha yoga program designed for
      seniors. These adaptations corresponded with the previously reported
      biomechanical demands of the poses.

PMID- 27885331
TI  - Guided Growth of Horizontal p-Type ZnTe Nanowires.
AB  - A major challenge toward large-scale integration of nanowires is the control over
      their alignment and position. A possible solution to this challenge is the guided
      growth process, which enables the synthesis of well-aligned horizontal nanowires
      that grow according to specific epitaxial or graphoepitaxial relations with the
      substrate. However, the guided growth of horizontal nanowires was demonstrated
      for a limited number of materials, most of which exhibit unintentional n-type
      behavior. Here we demonstrate the vapor-liquid-solid growth of guided horizontal
      ZnTe nanowires and nanowalls displaying p-type behavior on four different planes
      of sapphire. The growth directions of the nanowires are determined by epitaxial
      relations between the nanowires and the substrate or by a graphoepitaxial effect
      that guides their growth along nanogrooves or nanosteps along the surface. We
      characterized the crystallographic orientations and elemental composition of the
      nanowires using transmission electron microscopy and photoluminescence. The
      optoelectronic and electronic properties of the nanowires were studied by
      fabricating photodetectors and top-gate thin film transistors. These measurements
      showed that the guided ZnTe nanowires are p-type semiconductors and are
      photoconductive in the visible range. The guided growth of horizontal p-type
      nanowires opens up the possibility of parallel nanowire integration into
      functional systems with a variety of potential applications not available by
      other means.

PMID- 27885332
TI  - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucoside Promotes Expression of the
      Longevity Gene Klotho.
AB  - The longevity gene klotho has numerous physiological functions, such as
      regulating calcium and phosphorus levels, delaying senescence, improving
      cognition, reducing oxidative stress, and protecting vascular endothelial cells.
      This study tested whether 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucoside
      (THSG), a small molecule with antiaging effects, regulates the expression and
      physiological effects of klotho. Our results showed that THSG dose-dependently
      increased the luciferase reporter activity of the klotho gene, reversed the
      decrease in mRNA and protein expression of klotho which was induced by
      angiotensin II in NRK-52E renal tubular epithelial cells, and increased klotho
      mRNA expression in the cerebral cortex, hippocampus, testis, and kidney medulla
      of spontaneously hypertensive rats. THSG also reduced the number of senescent
      cells induced by angiotensin II and improved the antioxidant capacity and
      enhanced the bone strength in vivo. Based on klotho's role in promoting
      cognition, regulating bone metabolism, and improving renal function, the effect
      of THSG on klotho expression will be beneficial to the functional improvement or
      enhancement of the expressed organs or tissues.

PMID- 27885333
TI  - Astragalus Polysaccharide Suppresses 6-Hydroxydopamine-Induced Neurotoxicity in
      Caenorhabditis elegans.
AB  - Astragalus membranaceus is a medicinal plant traditionally used in China for a
      variety of conditions, including inflammatory and neural diseases. Astragalus
      polysaccharides are shown to reduce the adverse effect of levodopa which is used
      to treat Parkinson's disease (PD). However, the neuroprotective effect of
      Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans
      models, we investigated the protective effect of astragalan, an acidic
      polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6
      hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that
      6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of
      food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these
      degenerative symptoms can be attenuated by astragalan treatment. Astragalan is
      also shown to alleviate oxidative stress through reducing reactive oxygen species
      level and malondialdehyde content and increasing superoxide dismutase and
      glutathione peroxidase activities and reduce the expression of proapoptotic gene
      egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is
      capable of elevating the decreased acetylcholinesterase activity induced by 6
      OHDA. Together, our results demonstrate that the protective effect of astragalan
      against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress
      and regulation of apoptosis pathway and cholinergic system and thus provide an
      important insight into the therapeutic potential of Astragalus polysaccharide in
      neurodegeneration.

PMID- 27885335
TI  - Rapid Synthesis of Redox-Active Dodecaborane B12(OR)12 Clusters Under Ambient
      Conditions.
AB  - We have developed a fast and efficient route to obtain perfunctionalized ether
      linked alkyl and benzyl derivatives of the closo-[B12(OH)12]2- icosahedral
      dodecaborate cluster via microwave-assisted synthesis. These icosahedral boron
      clusters exhibit three-dimensional delocalization of the cage-bonding electrons,
      tunable photophysical properties, and a high degree of stability in air in both
      solid and solution states. A series of closo-[B12(OR)12]2-, hypocloso
      [B12(OR)12]1- and hypercloso-[B12(OR)12]0 clusters have been prepared with
      reaction times ranging from hours to several minutes. This method is superior to
      previously reported protocols since it dramatically decreases the reaction times
      required and eliminates the need for inert atmosphere conditions. The generality
      of the new microwave-based method has been further demonstrated through the
      synthesis of several new derivatives, which feature redox potentials up to 0.6 V
      more positive than previously known B12(OR)12 cluster compounds. We further show
      how this method can be applied to a one-pot synthesis of hybrid, vertex
      differentiated species B12(OR)11(OR) that was formerly accessible only via multi
      step reaction sequence.

PMID- 27885334
TI  - (-)-Epicatechin Prevents Blood Pressure Increase and Reduces Locomotor
      Hyperactivity in Young Spontaneously Hypertensive Rats.
AB  - This study investigated the effects of subchronic (-)-epicatechin (Epi) treatment
      on locomotor activity and hypertension development in young spontaneously
      hypertensive rats (SHR). Epi was administered in drinking water (100 mg/kg/day)
      for 2 weeks. Epi significantly prevented the development of hypertension (138 +/-
      2 versus 169 +/- 5 mmHg, p < 0.001) and reduced total distance traveled in the
      open-field test (22 +/- 2 versus 35 +/- 4 m, p < 0.01). In blood, Epi
      significantly enhanced erythrocyte deformability, increased total antioxidant
      capacity, and decreased nitrotyrosine concentration. In the aorta, Epi
      significantly increased nitric oxide (NO) synthase (NOS) activity and elevated
      the NO-dependent vasorelaxation. In the left heart ventricle, Epi increased NOS
      activity without altering gene expressions of nNOS, iNOS, and eNOS. Moreover, Epi
      reduced superoxide production in the left heart ventricle and the aorta. In the
      brain, Epi increased nNOS gene expression (in the brainstem and cerebellum) and
      eNOS expression (in the cerebellum) but had no effect on overall NOS activity. In
      conclusion, Epi prevented the development of hypertension and reduced locomotor
      hyperactivity in young SHR. These effects resulted from improved cardiovascular
      NO bioavailability concurrently with increased erythrocyte deformability, without
      changes in NO production in the brain.

PMID- 27885336
TI  - Investigation of Structural Dynamics of Enzymes and Protonation States of
      Substrates Using Computational Tools.
AB  - This review discusses the use of molecular modeling tools, together with existing
      experimental findings, to provide a complete atomic-level description of enzyme
      dynamics and function. We focus on functionally relevant conformational dynamics
      of enzymes and the protonation states of substrates. The conformational
      fluctuations of enzymes usually play a crucial role in substrate recognition and
      catalysis. Protein dynamics can be altered by a tiny change in a molecular system
      such as different protonation states of various intermediates or by a significant
      perturbation such as a ligand association. Here we review recent advances in
      applying atomistic molecular dynamics (MD) simulations to investigate allosteric
      and network regulation of tryptophan synthase (TRPS) and protonation states of
      its intermediates and catalysis. In addition, we review studies using quantum
      mechanics/molecular mechanics (QM/MM) methods to investigate the protonation
      states of catalytic residues of beta-Ketoacyl ACP synthase I (KasA). We also
      discuss modeling of large-scale protein motions for HIV-1 protease with coarse
      grained Brownian dynamics (BD) simulations.

PMID- 27885337
TI  - The Nonmydriatic Fundus Camera in Diabetic Retinopathy Screening: A Cost
      Effective Study with Evaluation for Future Large-Scale Application.
AB  - Aims. The study aimed to present the experience of a screening programme for
      early detection of diabetic retinopathy (DR) using a nonmydriatic fundus camera,
      evaluating the feasibility in terms of validity, resources absorption, and future
      advantages of a potential application, in an Italian local health authority.
      Methods. Diabetic patients living in the town of Ponzano, Veneto Region (Northern
      Italy), were invited to be enrolled in the screening programme. The "no
      prevention strategy" with the inclusion of the estimation of blindness related
      costs was compared with screening costs in order to evaluate a future extensive
      and feasible implementation of the procedure, through a budget impact approach.
      Results. Out of 498 diabetic patients eligible, 80% was enrolled in the screening
      programme. 115 patients (34%) were referred to an ophthalmologist and 9 cases
      required prompt treatment for either proliferative DR or macular edema. Based on
      the pilot data, it emerged that an extensive use of the investigated screening
      programme, within the Greater Treviso area, could prevent 6 cases of blindness
      every year, resulting in a saving of ?271,543.32 (-13.71%). Conclusions. Fundus
      images obtained with a nonmydriatic fundus camera could be considered an
      effective, cost-sparing, and feasible screening tool for the early detection of
      DR, preventing blindness as a result of diabetes.

PMID- 27885338
TI  - Effects of Intravitreal Ranibizumab Injection on Chinese Patients with Wet Age
      Related Macular Degeneration: 5-Year Follow-Up Results.
AB  - Purpose. To observe the effect of intravitreal ranibizumab injection on wet age
      related macular degeneration (wAMD) over 5 years in Chinese patients. Methods.
      Thirty-seven patients who were diagnosed with wAMD in our hospital from June 2007
      to June 2014 were retrospectively reviewed. The PRN regimen and the treatment and
      extend regimen were applied. Best corrected visual acuity (BCVA), number of
      ranibizumab injections, and changes in the choroidal neovascularization (CNV)
      lesion over 5 years were analyzed. Results. The mean BCVA measured by the ETDRS
      chart at baseline was 47.4 and 5 years after the treatment it was 34.89 letters,
      which was significantly different (p = 0.013). Fourteen eyes (37.8%) had improved
      visual acuity after 5 years. The number of injections in 5 years was 11.53, and
      most of the injections were in the first two years. Seventeen (45.9%) cases
      developed fibrous lesions, and 2 (5.4%) cases had atrophic lesions after 5 years.
      The fibrosis/atrophy was significantly correlated with the injection numbers
      (Pearson, r = 0.663, and p = 0.000). Conclusion. Most of the patients can
      maintain visual acuity treated by ranibizumab in the first 3 years. After 5
      years, some patients can still improve or maintain visual acuity. Fibrous
      scarring of the lesion is the main reason for a decrease in vision of wAMD
      patients.

PMID- 27885339
TI  - Establishing Waist-to-Height Ratio Standards from Criterion-Referenced BMI Using
      ROC Curves in Low-Income Children.
AB  - The purpose of this study was to establish health-related waist-to-height ratio
      (WHtR) cut-points associating with FITNESSGRAM's body mass index (BMI) criterion
      referenced standards in low-income children. A secondary aim was to examine the
      classification agreement between the derived WHtR cut-points and various
      cardiometabolic blood markers using current recommendations. Participants were
      219 children from low-income schools (mean age = 10.5 +/- 0.6 years). Waist
      circumference, height, weight, and cardiometabolic blood markers were collected
      in a fasting state before school hours. Receiver operating characteristic (ROC)
      curves were used to determine WHtR cut-points that associated with a child
      meeting FITNESSGRAM's age- and sex-specific criterion-referenced standards for
      BMI. The derived WHtR cut-point was 0.50 (AUC = 0.89, p < 0.001; sensitivity =
      0.86, specificity = 0.82, and accuracy = 84.3%). Classification agreement using
      the derived WHtR cut-point with various blood marker standards was statistically
      significant but considered weak to fair (kappa 0.14-0.34, agreement = 59%-67%,
      and p < 0.01). The WHtR cut-point of 0.50 can be used with strong accuracy to
      distinguish low-income children who met FITNESSGRAM's criterion-referenced
      standards for body composition; however, the evidence was weaker for its use in
      distinguishing low-income children meeting specific cardiometabolic blood marker
      recommendations.

PMID- 27885341
TI  - Characteristics of the Relationship of Kidney Dysfunction with Cardiovascular
      Disease in High Risk Patients with Diabetes.
AB  - We aimed at comparing the relationship of reduced estimated glomerular filtration
      rate (eGFR) with cardiovascular disease (CVD) and mortality between high risk
      patients with and without type 2 diabetes mellitus (T2DM). The cross-sectional
      study evaluated 16,298 participants (1,627 T2DM) acutely admitted to hospital.
      The longitudinal study comprised 7,508 patients (673 with diabetes and 6,835
      without). eGFR was categorized into 6 stages from >90 to <15 mL/min/1.73 m2.
      Kidney dysfunction was defined by an eGFR < 60 mL/min/1.73 m2. Patients with T2D
      showed a higher prevalence of CVD (37.9% versus 23.6%; P < 0.001) and kidney
      dysfunction (25% versus 13.2%; P < 0.001) than in the general population. An
      association with CVD was found with eGFR stages from 30 to 90 mL/min/1.73 m2 in
      T2D and from <15 to 90 mL/min/1.73 m2 in general population, in whom the
      association of eGFR with coronary heart disease was in an inverse relationship (P
      < 0.01 for trend). Survival, in diabetes, was lower (P = 0.037) but not
      associated with kidney dysfunction. Conclusions. In a high risk population,
      patients admitted to hospital, the relationship of kidney function with CVD is
      different between T2D and the general population. Competing mortality and the
      presence of other major risk factors in diabetes may be responsible for this
      difference.

PMID- 27885340
TI  - Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review.
AB  - Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment
      strategy for lymphoproliferative disorders and bone marrow failure states
      including aplastic anemia and thalassemia. However, its use has been limited by
      the increased treatment related complications, including acute kidney injury
      (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been
      associated with an increased risk of mortality. The incidence of AKI reported in
      recipients of myeloablative allogeneic transplant is considerably higher in
      comparison to other subclasses mainly due to use of cyclosporine and development
      of graft-versus-host disease (GVHD) in allogeneic groups. Acute GVHD is by itself
      a major independent risk factor for the development of AKI in HSCT recipients.
      The other major risk factors are sepsis, nephrotoxic medications (amphotericin B,
      acyclovir, aminoglycosides, and cyclosporine), hepatic sinusoidal obstruction
      syndrome (SOS), thrombotic microangiopathy (TMA), marrow infusion toxicity, and
      tumor lysis syndrome. The mainstay of management of AKI in these patients is
      avoidance of risk factors contributing to AKI, including use of reduced intensity
      conditioning regimen, close monitoring of nephrotoxic medications, and use of
      alternative antifungals for prophylaxis against infection. Also, early
      identification and effective management of sepsis, tumor lysis syndrome, marrow
      infusion toxicity, and hepatic SOS help in reducing the incidence of AKI in HSCT
      recipients.

PMID- 27885343
TI  - Qualitative Inquiry into Challenges Experienced by Registered General Nurses in
      the Emergency Department: A Study of Selected Hospitals in the Volta Region of
      Ghana.
AB  - Registered General Nurses (RGNs) play crucial roles in emergency departments
      (EDs). EDs in Ghana are primarily staffed by RGNs who have had no additional
      formal education in emergency care. Additionally, basic, master's, or doctoral
      level nursing education programs provide limited content on the complexities of
      emergency nursing. Nurses in EDs are affected by many challenges such as growing
      patient population, financial pressures, physical violence, verbal abuse,
      operational inefficiencies, overcrowding, and work overload. There is a paucity
      of research on challenges experienced by RGNs in EDs in the Volta Region of
      Ghana. In this qualitative study, twenty RGNs in EDs from three selected
      hospitals in the Volta Region of Ghana were interviewed. All recorded interviews
      were transcribed, reviewed several times by researchers and supervisors, and
      analyzed using content analysis. Five thematic categories were identified. These
      thematic categories of challenges were lack of preparation for ED role, verbal
      abuse from patients relatives, lack of resources in ED, stressful and time
      consuming nature of ED, and overcrowding in ED. Formal education of RGNs in the
      advanced role of emergency care, adequate supply of resources, increased hospital
      management support, and motivations for RGNs working in ED are necessary to
      improve the practice of emergency care.

PMID- 27885342
TI  - Venous Adventitial Cystic Disease: A Review of 45 Cases Treated Since 1963.
AB  - Purpose. To review and identify the most accurate ways of diagnosing and treating
      adventitial cystic disease (ACD) of the venous system. Methods. Cases of ACD were
      collected through three popular medical databases, including PubMed, Cochrane,
      OVID, and MEDLINE. After reviewing the literature, the sites of occurrence of 323
      cases of adventitial cystic disease were documented, and all cases of arterial
      ACD were excluded. The clinical features, treatment, and subsequent course of 45
      cases of venous ACD are included in this paper. Results. After reviewing all 45
      cases of venous ACD , we have confirmed that the most common vessel affected is
      the common femoral vein, which reproduces the most common symptom of venous ACD:
      asymmetric lower extremity swelling worsening over time. Conclusion. Venous ACD
      most commonly affects the common femoral vein. When unilateral leg swelling
      occurs with or without a noticeable mass, ACD should be considered. It is best
      confirmed with CT venography and the treatment of choice is transluminal cyst
      evacuation and excision.

PMID- 27885344
TI  - Drug-Induced Hypersensitivity Syndrome Caused by Carbamazepine Used for the
      Treatment of Trigeminal Neuralgia.
AB  - An 88-year-old man was diagnosed with trigeminal neuralgia, and treatment of
      carbamazepine 200 mg/day was initiated. About 6 weeks later, the patient
      developed a skin rash accompanied by fever. He was admitted to hospital and
      diagnosed with drug-induced hypersensitivity syndrome (DIHS) caused by
      carbamazepine. Oral carbamazepine treatment was stopped, but blood tests showed
      acute liver and acute renal failure. Drug-induced lymphocyte stimulation test
      (DLST) for carbamazepine, human herpes virus-6 (HHV-6) IgG, and CMV-HRP were
      negative. Oral prednisolone therapy was begun 18 days later. The titer of HHV-6
      IgG antibodies was then detected (640 times). Following treatment, liver and
      renal function improved and the erythema disappeared.

PMID- 27885345
TI  - Effectiveness of Long Term Supervised and Assisted Physiotherapy in Postsurgery
      Oral Submucous Fibrosis Patients.
AB  - Oral submucous fibrosis is one of the leading potentially malignant disorders
      prevailing in India. A number of conservative and surgical treatment options have
      been suggested for this potentially malignant disorder (Arakeri and Brennan,
      2013). While the role of physiotherapy has been highlighted in the conservative
      management, its importance in postsurgical cases to avoid scar contracture and
      subsequent relapse has not been given due importance in the literature. The
      following is a case report of a male patient surgically treated for OSMF (oral
      submucous fibrosis) and meticulously followed up for recalls and physiotherapy.
      The constant supervision and motivation for physiotherapy along with the constant
      assistance helped achieve satisfying results.

PMID- 27885347
TI  - Fludarabine Treatment of Patient with Chronic Lymphocytic Leukemia Induces a
      Digital Ischemia.
AB  - We report a 63-year-old man with a history of chronic lymphocytic leukemia (CLL)
      who presented with asymmetrical Raynaud's phenomenon of sudden onset which
      progressed to acral gangrene rapidly in a week. These symptoms began
      approximately one week after the fourth cycle of fludarabine and cyclophosphamide
      chemotherapy and were accompanied by pain, numbness, and cyanosis in the fingers
      of his right hand except the first finger. Fludarabine may play a role in acral
      vascular syndrome. The treatment with fludarabine in patients with evolving
      digital ischemia should be carried out with caution.

PMID- 27885346
TI  - Association between Oesophageal Diverticula and Leiomyomas: A Report of Two
      Cases.
AB  - We report two rare cases of female patients presenting with oesophageal leiomyoma
      associated with oesophageal diverticulum, both of whom were surgically managed.
      Oesophageal leiomyoma and oesophageal diverticulum are uncommon as separate
      entities and rare as combined disease presentation. Clinicians need to be aware
      of the rare combination of the two entities and need to be able to exclude the
      presence of a tumour (benign or malignant) within a diverticulum and so plan the
      optimum treatment. Herein, we present two cases of oesophageal leiomyoma within
      oesophageal diverticulum and we try to elucidate the association between the two.
      To date, there is no consensus whether a diverticulum is secondary to a leiomyoma
      or, on the contrary, a leiomyoma arises within a diverticulum.

PMID- 27885349
TI  - Chronic Lymphocytic Leukemia with Translocation (2;14)(p16;q32): A Case Report
      and Review of the Literature.
AB  - We report the case of a young African American male with no significant past
      medical history presenting with low back and bilateral leg pain; presenting CBC
      and chemistries revealed elevated white blood cell count of 250,000, with anemia
      (Hb 6.8 g/dL) and thrombocytopenia (platelets 9 K/MUL), and elevated LDH, 1008.
      Physical examination findings were notable for diffuse lymphadenopathy and lower
      extremity skin nodules. Interestingly the bone marrow biopsy revealed involvement
      by CLL/SLL with translocation (2;14)(p16;q32) and trisomy 12. The patient was
      treated with fludarabine-based chemotherapy and steroids for CLL-related ITP with
      excellent response. After three cycles of chemotherapy, all the enlarged lymph
      nodes and skin nodules disappeared, and patient had achieved complete hematologic
      response. In this paper we also reviewed the available literature of CLL patients
      with translocation (2;14).

PMID- 27885348
TI  - Should Prophylactic Anticoagulation Be Considered with Large Uterine Leiomyoma? A
      Case Series and Literature Review.
AB  - Introduction. Uterine leiomyomas, also called uterine fibroids or myomas, are the
      most common pelvic tumors in women. They are very rarely the cause of acute
      complications. However, when complications occur they cause significant morbidity
      and mortality. Thromboembolic disease has been described as a rare complication
      of uterine leiomyomas. DVT is a serious illness, sometimes causing death due to
      acute PE. Cases. We report a case series of 3 patients with thromboembolic
      disease associated with uterine leiomyoma at Hurley Medical Center, Flint,
      Michigan, during 2015 and conduct a literature review on the topic. A literature
      search was conducted using Medline, PubMed, and PMC databases from 1966 to 2015.
      Conclusion. The uterine leiomyoma is a very rare cause of PE and only few cases
      have been reported. DVT secondary to uterine leiomyoma should be considered in a
      female presenting with abdominal mass and pelvic pressure, if there is no clear
      common cause for her symptoms. Thromboembolic disease secondary to large uterine
      leiomyoma should be treated with acute stabilization and then hysterectomy.
      Prophylactic anticoagulation would be beneficial for lowering the risk of VTE in
      patients with large uterine leiomyoma.

PMID- 27885350
TI  - A Case of Dermatomyositis and Anti-EJ Autoantibody with Chronic Intestinal
      Pseudoobstruction Successfully Treated with Octreotide.
AB  - Chronic intestinal pseudoobstruction (CIPO) is a serious complication in patients
      with connective tissue disease (CTD) and is sometimes life-threatening or fatal
      despite intensive medical treatment. Here, we report a patient with
      dermatomyositis (DM) and anti-EJ autoantibody who developed CIPO that was
      improved by octreotide. Because her abdominal pain and bloatedness were so severe
      and persistent, we introduced octreotide to relieve symptoms. In this case,
      continuous intravenous administration as well as long-acting subcutaneous
      injection of octreotide was effective for treating CIPO.

PMID- 27885352
TI  - Formulation and Evaluation of Antibacterial Creams and Gels Containing Metal Ions
      for Topical Application.
AB  - Background. Skin infections occur commonly and often present therapeutic
      challenges to practitioners due to the growing concerns regarding multidrug
      resistant bacterial, viral, and fungal strains. The antimicrobial properties of
      zinc sulfate and copper sulfate are well known and have been investigated for
      many years. However, the synergistic activity between these two metal ions as
      antimicrobial ingredients has not been evaluated in topical formulations.
      Objective. The aims of the present study were to (1) formulate topical creams and
      gels containing zinc and copper alone or in combination and (2) evaluate the in
      vitro antibacterial activity of these metal ions in the formulations. Method.
      Formulation of the gels and creams was followed by evaluating their organoleptic
      characteristics, physicochemical properties, and in vitro antibacterial activity
      against Escherichia coli and Staphylococcus aureus. Results. Zinc sulfate and
      copper sulfate had a strong synergistic antibacterial activity in the creams and
      gels. The minimum effective concentration was found to be 3 w/w% for both active
      ingredients against the two tested microorganisms. Conclusions. This study
      evaluated and confirmed the synergistic in vitro antibacterial effect of copper
      sulfate and zinc sulfate in a cream and two gels.

PMID- 27885351
TI  - Coronary Angiography Safety between Transradial and Transfemoral Access.
AB  - Background and Aim. The aim of study was to evaluate safety, feasibility, and
      procedural variables of transradial approach compared with transfemoral approach
      in a standard population of patients undergoing coronary catheterization as one
      of the major criticisms of the transradial approach is that it takes longer
      overall procedure and fluoroscopy time, thereby causing more radiation exposure.
      Method. Between January 2015 and December 2015, a total of 1,997 patients in LPS
      Institute of Cardiology, GSVM Medical College, Kanpur, UP, India, undergoing
      coronary catheterization were randomly assigned to the transradial or
      transfemoral approach. Result. Successful catheterization was achieved in 1045 of
      1076 patients (97.1%) in the transradial group and in 918 of 921 patients (99.7%)
      in the transfemoral group (p = 0.001). Comparing the transradial and transfemoral
      approaches, fluoroscopy time (2.46 +/- 1.22 versus 2.83 +/- 1.31 min; p = 0.32),
      procedure time (8.89 +/- 2.72 versus 9.33 +/- 2.82 min; p = 0.56), contrast
      volume (67.52 +/- 22.54 versus 71.63 +/- 25.41 mL; p = 0.32), radiation dose as
      dose area product (24.2 +/- 4.21 versus 22.3 +/- 3.46 Gycm2; p = 0.43), and
      postprocedural rise of serum creatinine (6 +/- 4.5% versus 8 +/- 2.6%; p = 0.41)
      were not significantly different while vascular access site complications were
      significantly lower in transradial group than transfemoral group (3.9% versus
      7.6%; p = 0.04). Conclusion. The present study shows that transradial access for
      coronary angiography is safe among patients compared to transfemoral access with
      lower rate of local vascular complications.

PMID- 27885353
TI  - A Comparison of the Effects of Alpha and Medical-Grade Honey Ointments on
      Cutaneous Wound Healing in Rats.
AB  - Introduction. This study compared the healing efficacy and possible adverse
      effects of topical Alpha and medical-grade honey ointments on cutaneous wounds in
      rats. Methods. To conduct the study, 22 male Sprague-Dawley rats were randomly
      allocated into two equal groups: (1) rats with Alpha ointment applied to the
      wound surface area and (2) rats with medical-grade honey ointment applied to
      their wounds. The ointments were applied daily during the 21-day study period.
      Wound contraction was examined photographically with images taken on days 0, 7,
      and 21 after wounding. The healing process was histopathologically assessed using
      skin biopsies taken from the wound sites on days 7 and 21. Results. No
      statistically significant difference in mean wound surface area was observed
      between the two study groups. According to histopathological assessment, a
      significant reduction in the amount of collagen deposition (P value: 0.007) and
      neovascularisation (P value: 0.002) was seen in the Alpha-treated rats on day 21.
      No tissue necrosis occurred following the application of Alpha ointment.
      Conclusion. Daily topical usage of Alpha ointment on a skin wound can negatively
      affect the healing process by inhibiting neovascularization. Topical Alpha
      ointment can reduce the possibility of excessive scar formation by reducing
      collagen deposition.

PMID- 27885354
TI  - A Potential Biofilm Metabolite Signature for Caries Activity - A Pilot Clinical
      Study.
AB  - BACKGROUND: This study's aim was to compare the dental biofilm metabolite-profile
      of caries-active (N=11) or caries-free (N=4) children by gas chromatography-mass
      spectrometry (GC/MS) analyses. METHODS: Samples collected after overnight
      fasting, with or without a previous glucose rinse, were combined for each child
      based on the caries status of the site, re-suspended in ethanol and analyzed by
      GC/MS. RESULTS: Biofilm from caries-active sites exhibited a different
      chromatographic profile compared to caries-free sites. Qualitative and
      quantitative analysis suggested a special cluster of branched alcohols and esters
      present at substantially higher intensity in biofilms of caries-active sites.
      CONCLUSIONS: This pilot study indicates that there are metabolites present in the
      biofilm which have the potential to provide a characteristic metabolomics
      signature for caries activity.

PMID- 27885355
TI  - Applying the Mini-Open Anterolateral Lumbar Interbody Fusion with Self-Anchored
      Stand-Alone Polyetheretherketone Cage in Lumbar Revision Surgery.
AB  - The author retrospectively studied twenty-two patients who underwent revision
      lumbar surgeries using ALLIF with a self-anchored stand-alone
      polyetheretherketone (PEEK) cage. The operation time, blood loss, and
      perioperative complications were evaluated. Oswestry disability index (ODI)
      scores and visual analog scale (VAS) scores of leg and back pain were analyzed
      preoperatively and at each time point of postoperative follow-up. Radiological
      evaluation including fusion, disc height, foraminal height, and subsidence was
      assessed. The results showed that the ALLIF with a self-anchored stand-alone PEEK
      cage is safe and effective in revision lumbar surgery with minor surgical trauma,
      low access-related complication rates, and satisfactory clinical and radiological
      results.

PMID- 27885356
TI  - Magnetization Transfer and Amide Proton Transfer MRI of Neonatal Brain
      Development.
AB  - Purpose. This study aims to evaluate the process of brain development in neonates
      using combined amide proton transfer (APT) imaging and conventional magnetization
      transfer (MT) imaging. Materials and Methods. Case data were reviewed for all
      patients hospitalized in our institution's neonatal ward. Patients underwent APT
      and MT imaging (a single protocol) immediately following the routine MR
      examination. Single-slice APT/MT axial imaging was performed at the level of the
      basal ganglia. APT and MT ratio (MTR) measurements were performed in multiple
      brain regions of interest (ROIs). Data was statistically analyzed in order to
      assess for significant differences between the different regions of the brain or
      correlation with patient gestational age. Results. A total of 38 neonates were
      included in the study, with ages ranging from 27 to 41 weeks' corrected
      gestational age. There were statistically significant differences in both APT and
      MTR measurements between the frontal lobes, basal ganglia, and occipital lobes
      (APT: frontal lobe versus occipital lobe P = 0.031 and other groups P = 0.00;
      MTR: frontal lobe versus occipital lobe P = 0.034 and other groups P = 0.00).
      Furthermore, APT and MTR in above brain regions exhibited positive linear
      correlations with patient gestational age. Conclusions. APT/MT imaging can
      provide valuable information about the process of the neonatal brain development
      at the molecular level.

PMID- 27885358
TI  - Miniopen Transforaminal Lumbar Interbody Fusion with Unilateral Fixation: A
      Comparison between Ipsilateral and Contralateral Reherniation.
AB  - The aim of this study was to evaluate the risk factors between ipsilateral and
      contralateral reherniation and to compare the effectiveness of miniopen
      transforaminal lumbar interbody fusion (TLIF) with unilateral fixation for each
      group. From November 2007 to December 2014, clinical and radiographic data of
      each group (ipsilateral or contralateral reherniation) were collected and
      compared. Functional assessment (Visual Analog Scale (VAS) score and Japanese
      Orthopaedic Association (JOA)) and radiographic evaluation (fusion status, disc
      height, lumbar lordosis (LL), and functional spine unit (FSU) angle) were applied
      to compare surgical effect for each group preoperatively and at final followup.
      MacNab questionnaire was applied to further evaluate the satisfactory rate after
      the discectomy and fusion. No difference except pain-free interval was found
      between ipsilateral and contralateral groups. There was a significant difference
      in operative time between two groups. No differences were found in clinical and
      radiographic data for assessment of surgical effect between two groups. The
      satisfactory rate was decreasing in both groups with time passing after
      discectomy. Difference in pain-free interval may be a distinction for ipsilateral
      and contralateral reherniation. Miniopen TLIF with unilateral pedicle screw
      fixation can be a recommendable way for single level reherniation regardless of
      ipsilateral or contralateral reherniation.

PMID- 27885359
TI  - Corrigendum to "Nutritional Risk Factors for Age-Related Macular Degeneration".
AB  - [This corrects the article DOI: 10.1155/2014/413150.].

PMID- 27885360
TI  - Neurodegeneration: Etiologies and New Therapies 2016.

PMID- 27885357
TI  - Achilles Tendinopathy: Current Concepts about the Basic Science and Clinical
      Treatments.
AB  - Achilles tendinopathy is one of the most frequently ankle and foot overuse
      injuries, which is a clinical syndrome characterized by the combination of pain,
      swelling, and impaired performance. The two main categories of Achilles
      tendinopathy are classified according to anatomical location and broadly include
      insertional and noninsertional tendinopathy. The etiology of Achilles
      tendinopathy is multifactorial including both intrinsic and extrinsic factors.
      Failed healing response and degenerative changes were found in the tendon. The
      failed healing response includes three different and continuous stages (reactive
      tendinopathy, tendon disrepair, and degenerative tendinopathy). The histological
      studies have demonstrated an increased number of tenocytes and concentration of
      glycosaminoglycans in the ground substance, disorganization and fragmentation of
      the collagen, and neovascularization. There are variable conservative and
      surgical treatment options for Achilles tendinopathy. However, there has not been
      a gold standard of these treatments because of the controversial clinical results
      between various studies. In the future, new level I researches will be needed to
      prove the effect of these treatment options.

PMID- 27885361
TI  - First principles search for n-type oxide, nitride, and sulfide thermoelectrics.
AB  - Oxides have many potentially desirable characteristics for thermoelectric
      applications, including low cost and stability at high temperatures, but thus far
      there are few known high zT n-type oxide thermoelectrics. In this work, we use
      high-throughput first principles calculations to screen transition metal oxides,
      nitrides, and sulfides for candidate materials with high power factors and low
      thermal conductivity. We find a variety of promising materials, and we
      investigate these materials in detail in order to understand the mechanisms that
      cause them to have high power factors. These materials all combine a high density
      of states near the Fermi level with dispersive bands, reducing the trade-off
      between the Seebeck coefficient and the electrical conductivity, but they do so
      for several different reasons. In addition, our calculations indicate that many
      of our candidate materials have low thermal conductivity.

PMID- 27885363
TI  - Mitotic Protein Kinase 1: Role in Spindle Assembly Checkpoint Revisited.

PMID- 27885364
TI  - Bidirectional RNN for Medical Event Detection in Electronic Health Records.
AB  - Sequence labeling for extraction of medical events and their attributes from
      unstructured text in Electronic Health Record (EHR) notes is a key step towards
      semantic understanding of EHRs. It has important applications in health
      informatics including pharmacovigilance and drug surveillance. The state of the
      art supervised machine learning models in this domain are based on Conditional
      Random Fields (CRFs) with features calculated from fixed context windows. In this
      application, we explored recurrent neural network frameworks and show that they
      significantly out-performed the CRF models.

PMID- 27885365
TI  - Hydrolysis of trivalent plutonium and solubility of Pu(OH)3 (am) under
      electrolytic reducing conditions.
AB  - The aim of this work is to determine the solubility product of plutonium
      hydroxide under reducing conditions and to ascertain the stability of Pu(OH)3
      (am) in water. Hydrolysis of Pu(iii) and solubility of Pu(OH)3 (am) were
      investigated at a constant ionic strength of 0.1 M NaClO4. Coulometric titration
      was adopted to adjust the pH of plutonium solutions, during which the
      electrolytic reducing conditions maintained the oxidation state of Pu(iii).
      Chemical speciation for dissolved plutonium was investigated using sensitive
      spectrophotometry coupled with a liquid waveguide capillary cell. The
      spectroscopic investigations indicated that dissolved Pu(iv), Pu(v), and Pu(vi)
      species were ignorable under these experimental conditions. The absorbance of
      Pu3+ ions decreased due to hydrolysis of Pu(iii) but the absorbance of Pu(iii)
      hydrolysis species was not distinguishable. The formation constant for the first
      hydrolysis species (log *beta'1) determined in the present study is -6.62 +/-
      0.25. The non-crystalline structure of the plutonium precipitate was observed
      through X-ray diffraction. The solubility product of Pu(OH)3 (am), log *K's,0 is
      determined to be 15.23 +/- 0.50. These results indicate a stronger tendency for
      the hydrolysis of Pu(iii) and higher stability (lower solubility) of Pu(OH)3 (am)
      compared to Am(iii).

PMID- 27885362
TI  - Current Rural Drug Use in the US Midwest.
AB  - The nature and challenge of illicit drug use in the United States continues to
      change rapidly, evolving in reaction to myriad social, economic, and local
      forces. While the use of illicit drugs affects every region of the country, most
      of our current information about drug use comes from large urban areas. Data on
      rural drug use and its harms justify greater attention. Record overdose rates,
      unexpected outbreaks of HIV, and a dearth of treatment facilities point to a
      rapidly worsening health situation. While health sciences have made considerable
      progress in understanding the etiology of drug use and uncovering the link
      between drug use and its myriad associated harms, this promising scientific news
      has not always translated to better health outcomes. The scope of the problem in
      the Central Plains of the US is growing, and can be estimated from available
      sources. Clear remedies for this rising level of abuse are available, but few
      have been implemented. Suggestions for short-term policy remedies are discussed.

PMID- 27885366
TI  - Controlling the magnetic properties of dysprosium metallofullerene within metal
      organic frameworks.
AB  - Magnetic endohedral metallofullerenes represent a new family of single-molecule
      magnets with a spherical form and solid framework. In this manuscript, we
      illustrate the controllable quantum tunneling of magnetism for metallofullerene
      DySc2N@C80 by means of molecule encapsulation in a porous metal-organic framework
      (MOF-177) with strong host-guest interactions.

PMID- 27885367
TI  - Olive oil and postprandial hyperlipidemia: implications for atherosclerosis and
      metabolic syndrome.
AB  - Olive oil is the primary source of fat in the Mediterranean diet, which is
      associated with a significant improvement in health status, as measured by
      reduced mortality from several chronic diseases. The current pandemic of obesity,
      metabolic syndrome, and type 2 diabetes is intimately associated with an
      atherogenic dyslipidemic phenotype. The core components of the dyslipidemia of
      the metabolic syndrome, which most likely initiate atherosclerosis, are the
      "lipid triad" consisting of high plasma triglycerides, low levels of high-density
      lipoproteins, and a preponderance of small, dense low-density lipoproteins at
      fasting. However, postprandial (non-fasting) TGs (postprandial hyperlipidemia)
      are also recognized as an important component for atherosclerosis. Herein, the
      purpose of this review was to provide an update on the effects and mechanisms
      related to olive oil on postprandial hyperlipidemia and its implications for the
      onset and progression of atherosclerosis and metabolic syndrome.

PMID- 27885368
TI  - Structural characterization of EasH (Aspergillus japonicus) - an oxidase involved
      in cycloclavine biosynthesis.
AB  - Aj_EasH is a non-heme iron- and alpha-keto-glutarate-dependent oxidase that is
      responsible for an unusual cyclopropyl ring formation in the biosynthesis of the
      fungal ergot alkaloid cycloclavine. The three dimensional structure of Aj_EasH
      (2.2 A resolution) reported here provides insight into the mechanism of this
      unusual and complex reaction.

PMID- 27885369
TI  - Electrospun poly(lactic acid) fibers containing novel chlorhexidine particles
      with sustained antibacterial activity.
AB  - The treatment of persistent infections often requires a high local drug
      concentration and sustained release of antimicrobial agents. This paper proposes
      the use of novel electrospinning of poly(lactic acid) (PLA) fibers containing
      uncoated and encapsulated chlorhexidine particles. Chlorhexidine particles with a
      mean (SD) diameter of 17.15 +/- 1.99 MUm were fabricated by the precipitation of
      chlorhexidine diacetate with calcium chloride. Layer-by-layer (LbL) encapsulation
      of the chlorhexidine particles was carried out to produce encapsulated particles.
      The chlorhexidine particles had a high chlorhexidine content (90%), and when they
      were electrospun into PLA fibers a bead-in-string structure was obtained. The
      chlorhexidine content in the fibers could be tuned and a sustained release over
      650 h was produced, via chlorhexidine particle encapsulation. Chlorhexidine
      release was governed by the polyelectrolyte multilayer encapsulation as
      demonstrated by SEM and confocal imaging. The incorporation of uncoated and
      encapsulated chlorhexidine particles (0.5% and 1% wt/wt chlorhexidine) into the
      fibers did not cause toxicity to healthy fibroblasts or affect cell adhesion to
      the fibers over a period of 5 days. The chlorhexidine-containing fibers also
      demonstrated sustained antibacterial activity against E. coli via an agar
      diffusion assay and broth transfer assay. Therefore, the chlorhexidine-containing
      PLA fibers may be useful in the treatment of persistent infections in medicine
      and dentistry.

PMID- 27885370
TI  - Water assisted high proton conductance in a highly thermally stable and superior
      water-stable open-framework cobalt phosphate.
AB  - Proton-conducting materials show important technological applications as key
      components in energy conversion, electrochemical sensing and electrochromic
      devices; the exploration for new types of proton-conducting materials is crucial
      for the development of efficient electrochemical devices. In this study, we
      investigated the proton transport nature of an inorganic-organic hybrid crystal
      of open-framework cobalt phosphate, (C2N2H10)0.5CoPO4. The structure of the
      hybrid crystal consists of the [CoPO4]-infinity anionic framework, and the proton
      carriers, H2en2+ cations (en = ethylenediamine), are located in the pores to
      compensate the negative charges of the inorganic framework. The open-framework is
      thermally stable up to 653 K (380  degrees C) at least, and also shows superior
      water stability. The open-framework exhibits negligible conductance in an
      anhydrous environment even at 473 K; however, there is evident water-assisted
      proton conduction. The conductivity reaches 2.05 * 10-3 S cm-1 at 329 K and 98%
      RH. Such high proton conductivity can compete with numerous state-of-the-art
      MOFs/PCPs-based proton conductors, and this material has promising applications
      in diverse electrochemical devices.

PMID- 27885371
TI  - Hierarchical ternary Ni-Co-Se nanowires for high-performance supercapacitor
      device design.
AB  - Large-scale uniform Ni-Co-Se bimetallic ternary nanowires have been successfully
      synthesized through a successive cation exchange. First, NiSe nanowires in situ
      grown on nickel foam (NF) were prepared by a facile solvothermal route. Next, a
      series of ternary materials possessing different proportions of Ni and Co were
      fabricated by a Co-exchange method using the Ni@NiSe material as a template,
      which effectively achieved morphological inheritance from the parent material. To
      explore the electrochemical performance, all synthetic materials were assembled
      into asymmetric supercapacitor devices. Among asymmetric supercapacitor devices,
      the Ni@Ni0.8Co0.2Se//active carbon (AC) device exhibited a high specific
      capacitance of 86 F g-1 at a current density of 1 A g-1 and excellent cycling
      stability with virtually no decrease in capacitance after 2000 continuous charge
      discharge cycles. This device still delivered an energy density of 17 Wh kg-1
      even at a high power density of 1526.8 W kg-1. These superior electrochemical
      properties of Ni@Ni0.8Co0.2Se as an electrode material for supercapacitor devices
      confirmed the synergistic effect between Co and Ni ions, suggesting their
      potential application in the field of energy storage.

PMID- 27885373
TI  - A new era of treatment for patients with haemophilia A?
AB  - Treatment and prevention of bleeding episodes in patients with severe haemophilia
      A require frequent intravenous injection of factor VIII. Inhibitory antibodies
      against factor VIII occur in approximately 30 % of these patients during the
      first exposure days and immune tolerance induction to eradicate the inhibitor is
      challenging. Prevention of bleeds in patients with haemophilia A and inhibitors
      is less effective and there is ongoing research for alternative treatment
      options. A promising approach in 2016 is the development of emicizumab (ACE910),
      a bi-specific IgG antibody to factor IXa and factor X, that mimics the cofactor
      function of factor VIII. Due to the different structure of this antibody it
      cannot be neutralized by factor VIII inhibitors and has the possibility to
      achieve haemostasis in patients with severe haemophilia A with and without
      inhibitors. First studies in healthy volunteers and in patients showed a
      shortened activated partial thromboplastin time and increased peak height of
      thrombin generation in a dose-dependent manner. The half-life of the drug was 4
      to 5 weeks. There were no clinical signs of thrombosis and no laboratory
      abnormalities indicating hypercoagulability. In a first study with 18 patients
      with severe haemophilia A with and without inhibitors a remarkable reduction in
      the annualised bleeding rate occurred. Safety of the drug has to be proven in
      ongoing research. Mimicking the cofactor activity of factor VIII by a bispecific
      antibody for the treatment of severe haemophilia A is so far safe and seems to be
      effective and is one highlight in haemostasis 2016.

PMID- 27885372
TI  - Treatment planning in PRRT based on simulated PET data and a PBPK model.
      Determination of accuracy using a PET noise model.
AB  - AIM: To investigate the accuracy of treatment planning in peptide-receptor
      radionuclide therapy (PRRT) based on simulated PET data (using a PET noise model)
      and a physiologically based pharmacokinetic (PBPK) model. METHODS: The parameters
      of a PBPK model were fitted to the biokinetic data of 15 patients. True
      mathematical phantoms of patients (MPPs) were the PBPK model with the fitted
      parameters. PET measurements after bolus injection of 150 MBq 68Ga-DOTATATE were
      simulated for the true MPPs. PET noise with typical noise levels was added to the
      data (i.e. c = 0.3 [low], 3, 30 and 300 [high]). Organ activity data in the
      kidneys, tumour, liver and spleen were simulated at 0.5, 1 and 4 h p.i. PBPK
      model parameters were fitted to the simulated noisy PET data to derive the PET
      predicted MPPs. Therapy was simulated assuming an infusion of 3.3 GBq of 90Y
      DOTATATE over 30 min. Time-integrated activity coefficients (TIACs) of simulated
      therapy in tumour, kidneys, liver, spleen and remainder were calculated from
      both, true MPPs (true TIACs) and predicted MPPs (predicted TIACs). Variability v
      between true TIACs and predicted TIACs were calculated and analysed. Variability
      <= 10 % was considered to be an accurate prediction. RESULTS: For all noise
      level, variabilities for the kidneys, liver, and spleen showed an accurate
      prediction for TIACs, e.g. c = 300: vkidney = (5 +/- 2)%, vliver = (5 +/- 2)%,
      vspleen = (4 +/- 2)%. However, tumour TIAC predictions were not accurate for all
      noise levels, e.g. c = 0.3: vtumour = (8 +/- 5)%. CONCLUSION: PET-based treatment
      planning with kidneys as the dose limiting organ seems possible for all reported
      noise levels using an adequate PBPK model and previous knowledge about the
      individual patient.

PMID- 27885374
TI  - Cardiovascular risk and inflammation in rheumatic diseases.

PMID- 27885375
TI  - Chylothorax in dermatomyositis complicated with interstitial pneumonia.
AB  - Chylothorax is a disease in which chyle leaks and accumulates in the thoracic
      cavity. Interstitial pneumonia and pneumomediastinum are common thoracic
      manifestations of dermatomyositis, but chylothorax complicated with
      dermatomyositis is not reported. We report a case of dermatomyositis with
      interstitial pneumonia complicated by chylothorax. A 77-year-old woman was
      diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5
      antibody and rapid progressive interstitial pneumonia. Treatment with
      betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was
      initiated, and her skin symptoms and interstitial pneumonia improved once.
      However, right-sided chylothorax began to accumulate and gradually increase, and
      at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers
      began to reappear on her fingers and auricles. Although her chylothorax improved
      by fasting and parenteral nutrition, she died due to further exacerbations of
      dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy,
      increase in the betamethasone dosage, additional intravenous high-dose
      cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as
      malignant tumors in the thoracic cavity. This is the first report of chylothorax
      complicated by dermatomyositis with interstitial pneumonia.

PMID- 27885376
TI  - High prevalence of subclinical atherosclerosis in psoriatic arthritis patients: a
      study based on carotid ultrasound.
AB  - Analyse the presence of subclinical atherosclerosis in psoriatic arthritis
      patients (PsA). A cross-sectional study of 53 patients with PsA and 53 controls
      matched for age and sex was designed. Carotid intima-media thickness (IMT) and
      the presence of carotid plaques (CP) were assessed with carotid ultrasound. Data
      on cardiovascular (CV) risk factors were collected. Patients with PsA had a
      higher prevalence rate of obesity and tobacco smoking. CP were detected more
      frequently in patients with PsA than in controls with an OR of 4.15, 95% CI 1.4
      12.1, which adjusted for smoking and those with history of CV disease gave an OR
      of 3.9, 95% CI 1.2-12.7, p = 0.026. Carotid IMT was significantly higher in
      patients with PsA adjusted for age and tobacco smoking. According to ultrasound
      data, 30.2% of patients with PsA had carotid atherosclerosis (presence of CP
      and/or carotid IMT > 0.90 mm) compared with 9.4% of controls. The SCORE index
      (Systematic Coronary Risk Evaluation) underestimated the CV risk in these
      patients: most patients with CP had an intermediate CV risk. According to carotid
      ultrasound data, PsA patients have a high prevalence of subclinical
      atherosclerosis. These results support the importance of screening for CV risk
      and to include carotid ultrasound in CV prevention strategies in these patients.

PMID- 27885377
TI  - [Partial pericardium defect with a cardiac heart diverticulum and extensive
      intrauterine hypoxic myocardial lesions].
AB  - The autopsy of a fetus at 23 weeks gestational age revealed a partial pericardial
      defect with subsequent herniation of parts of the left ventricle. The myocard was
      impinged by the fibrous rim of the residual pericardium. Microscopic examination
      showed signs of recurrent myocardial infarctions with necrosis, calcification,
      fibrosis and prominent deposition of iron.Partial pericardial defects result from
      incomplete fusion of the pleuropericardial membrane and may lead to myocardial
      infarction via compression of the coronary arteries.

PMID- 27885378
TI  - NETosis provides the link between activation of neutrophils on hemodialysis
      membrane and comorbidities in dialyzed patients.
AB  - INTRODUCTION: Neutrophil extracellular traps (NETs) are formed by activated
      neutrophils during the process of NETosis in which the nuclear material is
      released into extracellular space, including DNA molecules, citrullinated
      histones, and neutrophil granule enzymes, such as elastase. This material forms
      networks that are able not only to physically entrap bacteria but also to provide
      elevated concentration of bactericidal components. Over the last years, it has
      become clear that NETs can also be formed under numerous sterile inflammatory
      conditions, i.e., thrombosis, cancer, SLE, atherosclerosis, and diabetes. METHOD:
      We reviewed studies published until July 2016 to find possible associations
      between elevated cell-free DNA levels in dialyzed patients and the process of
      NETosis and its consequences. RESULTS: The process of NETosis, its elevated
      activation, or impaired clearance provides the link between clinical conditions
      and elevated levels of cell-free DNA found in plasma after the hemodialytic
      procedure which itself is able to activate neutrophils via platelets and ROS
      formation. NETs stimulate thrombosis and endothelial damage, and their formation
      may contribute to the development of spectrum of comorbidities described in
      dialyzed patients. CONCLUSION: The study of plasma cell-free DNA levels together
      with markers of NETosis could contribute to the evaluation of the influence of
      hemodialysis on the immune system of patients.

PMID- 27885381
TI  - Newborn with rhizomelia and  difficulty breathing.

PMID- 27885379
TI  - Preoperative radioactive seed localization of nonpalpable soft tissue masses: an
      established localization technique with a new application.
AB  - OBJECTIVE: To describe the technique of iodine125 (I125) seed deployment into
      nonpalpable soft tissue masses under direct ultrasound (US) or CT guidance for
      intraoperative localization. MATERIALS AND METHODS: Patients considered
      candidates for radioactive seed localization (RSL) based on advanced imaging
      findings underwent an ultrasound examination of the area of concern to verify
      sonographic visualization of the targeted mass. If the mass was not visible
      sonographically, CT was used for guidance. Patients were scheduled for surgery 1
      4 days after seed implantation. Intraoperative frozen section pathological
      analysis was performed on all patients. Operative time, specimen volume,
      intraoperative margin status, and final margin status were recorded. Following
      the surgery, patients and surgeons completed satisfaction surveys. RESULTS: Ten
      patients underwent seed placement between 1 and 4 days prior to surgery. All
      patients had successful surgical resection of the targeted mass with removal of
      all implanted radioactive seed(s). There was no seed migration. Intraoperative
      frozen-section margins were negative (>2 mm) in 6/10 patients. Final surgical
      margins were negative in 9/10 patients. The patient with a positive margin at
      final pathology did not undergo further resection due to the benign nature of the
      mass. Patient and surgeon satisfaction survey results were highly positive. All
      four surgeons reported a strong preference for seed localization over wire
      localization. CONCLUSIONS: RSL is an effective, reliable, and safe technique for
      preoperative localization of nonpalpable soft tissue masses and yields high
      patient and surgeon satisfaction.

PMID- 27885380
TI  - Anterior cruciate ligament reconstruction tunnel size: causes of tunnel
      enlargement and implications for single versus two-stage revision reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstructions have increased over the past 25
      years. The increased incidence of ACL reconstructions has translated into a
      larger number of graft failures and revision ACL procedures. It is important to
      understand the causes of graft failure when evaluating for a revision ACL
      reconstruction and to appreciate changes in tunnel anatomy over time prior to
      planning revision surgery. In this manuscript, tunnel size for ACL reconstruction
      and implications for single-stage versus two-stage revision ACL reconstruction
      will be discussed, as well as causes of tunnel enlargement, including mechanical
      and biological factors.

PMID- 27885382
TI  - MRI in flexor tendon rupture after collagenase injection.
AB  - Flexor tendon rupture is an unusual complication following collagenase injection
      to relieve contractures. These patients require a close follow-up and in the
      event of tendon rupture, a decision has to be made whether to repair the tendon
      or manage the complication conservatively. The authors report the utility of MRI
      in the prognostication and management of a patient with Dupuytren's contracture,
      who underwent collagenase injection and subsequently developed flexor digitorum
      profundus tendon rupture.

PMID- 27885384
TI  - Use of the arthroereisis screw with tendoscopic delivered platelet-rich plasma
      for early stage adult acquired flatfoot deformity.
AB  - PURPOSE: Early stage adult acquired flatfoot deformity (AAFD) is traditionally
      treated with osteotomy and tendon transfer. Despite a high success rate, the long
      recovery time and associated morbidity are not sufficient. This study aims to
      evaluate the functional and radiological outcomes following the use of the
      arthroereisis screw with tendoscopic delivered PRP for early stage AAFD. METHODS:
      Patients with stage IIa AAFD who underwent the use of the arthroereisis screw
      with tendoscopic delivered PRP with a minimum follow-up time of 24 months were
      retrospectively evaluated. Clinical outcomes for pain were evaluated with the
      Foot and Ankle Outcomes Score (FAOS) and Visual Analog Score (VAS). Radiographic
      deformity correction was assessed using weight-bearing imaging. RESULTS: Thirteen
      patients (13 feet) with mean follow-up of 29.5 months were included. The mean age
      was 37.3 years (range, 28-65 years). FAOS-reported symptoms, pain, daily
      activities, sports activities, and quality of life significantly improved from
      52.1, 42.6, 57.6, 35.7, and 15.4 pre-operatively to 78.5, 68.2, 83.3, 65.0, and
      49.6 post-operatively, respectively (p < 0.05). Statistically significant
      radiographic improvements (lateral talus first metatarsal angle, calcaneal pitch,
      and cuneiform to ground distance) were also observed between the pre- and post
      operative images. CONCLUSIONS: This study elucidates the successful
      implementation of a less invasive approach to stage IIa AAFD. Through the use of
      a subtalar arthroereisis screw, PTT tendoscopy, and PRP injection, clinical and
      radiographic outcomes were improved.

PMID- 27885385
TI  - In-Package Inactivation of Pathogenic and Spoilage Bacteria Associated with
      Poultry Using Dielectric Barrier Discharge-Cold Plasma Treatments.
AB  - The goal of this study was to test the efficacy of in-package dielectric barrier
      discharge-cold plasma (DBD-CP) treatment to inactivate poultry-associated
      spoilage (Pseudomonas fluorescens) and pathogenic (Salmonella enterica
      Typhimurium, Campylobacter jejuni) bacteria. Liquid cultures of the bacterial
      isolates were sealed within packages containing ambient air (Trial 1) or modified
      air (65% O2:30% CO2:5% N2; Trial 2). The packages were subjected to treatment
      times ranging from 30 to 180 s, and after 24 h incubation at 4  degrees C,
      bacterial titers were determined. The DBD-CP system completely inactivated the
      four isolates tested, although the in-package gas composition and treatment times
      were isolate-specific. Both C. jejuni isolates were completely inactivated
      between 30 s (modified air) and 120 s (ambient air), while modified air was
      required for the complete inactivation of S. typhimurium (90 s) and P.
      fluorescens (180 s). This DBD-CP system is effective for inactivating major
      poultry-associated spoilage and pathogenic bacteria in liquid culture, and
      through this study, system parameters to optimize inactivation were determined.
      This study demonstrates the potential for DBD-CP treatment to inactivate major
      bacteria of economic interest to the poultry industry, thus potentially allowing
      for reduced spoilage (e.g., longer shelf life) and increased safety of poultry
      products.

PMID- 27885383
TI  - Schwann cells: a new player in the tumor microenvironment.
AB  - Cancerous cells must cooperate with the surrounding stroma and non-malignant
      cells within the microenvironment to support the growth and invasion of the
      tumor. The nervous system is a component of every organ system of the body, and
      therefore, is invariably at the front line of the tumor invasion. Due to the
      complexity of the nervous system physiology, this review separately discusses the
      contributions of the central and peripheral nervous systems to the tumorigenesis
      and tumor progression. We further focus the discussion on the evidence that
      Schwann cells aid in tumor growth and invasion. Schwann cells, a largely
      unexplored element of the tumor microenvironment, may participate in the creation
      of tumor-favorable conditions through both bi-directional interaction with cancer
      cells and the facilitation of the immune-suppressive microenvironment through the
      mechanism of neural repair and immunomodulation.

PMID- 27885386
TI  - Wrist denervation of the posterior interosseous nerve through a volar approach: a
      new technique with anatomical considerations.
AB  - PURPOSE: Full or selective wrist denervation is an effective treatment for
      chronic wrist pain. In this cadaveric study, a volar approach for prophylactic
      denervation of the posterior interosseous nerve (PIN) and the anterior
      interosseous nerve (AIN) was assessed, which can simultaneously be performed
      during volar approaches for distal radius fracture fixation or in combination
      with metalwork removal. MATERIALS AND METHODS: In total 40 adult upper limbs,
      embalmed using Thiel's method, were investigated. Group 1 included 20 limbs of
      which the distances between AIN and PIN to the ulnar margin of radius were
      measured at levels 6, 8 and 10 cm proximal to the styloid process and the
      distance radial styloid process to proximal border of pronator quadratus which
      might be useful as an intraoperative landmark. Subsequently further additional 20
      adult limbs (group 2) were used. Transection of the PIN via this volar approach
      at the evaluated best level of step 1 was performed and evaluated by dissection
      via a dorsal approach. RESULTS: In group 1, the PIN runs within the interosseous
      membrane, from the ulnar border of the radius, 6.4 mm (SD 2.66) at 6 cm, 8.4 mm
      (SD 2.28) at 8 cm and 3.75 mm (SD 5.46) at 10 cm proximal to the radial styloid.
      The AIN runs within the interosseous membrane, from the ulna edge of the radius,
      7.5 mm (SD 2.4) at 6 cm, 7.3 mm (SD 1.95) at 8 cm and 2.35 mm (3.42) at 10 cm
      proximal to the radial styloid. AIN and PIN were in close proximity at the 8-cm
      level which equals a 1-cm distance proximal to the pronator quadratus border.
      Group 2 showed a successful transection of the PIN through a single volar
      surgical approach in additional 18 out of 20 adult upper limbs. CONCLUSIONS: This
      study shows the local anatomy of the PIN, allowing denervation via a volar
      approach.

PMID- 27885387
TI  - The Contribution of Project Environmental Assessment to Assessing and Managing
      Cumulative Effects: Individually and Collectively Insignificant?
AB  - This paper explores the opportunities and constraints to project-based
      environmental assessment as a means to support the assessment and management of
      cumulative environmental effects. A case study of the hydroelectric sector is
      used to determine whether sufficient information is available over time through
      project-by-project assessments to support an adequate understanding of cumulative
      change. Results show inconsistency from one project to the next in terms of the
      components and indicators assessed, limited transfer of baseline information
      between project assessments over time, and the same issues and concerns being
      raised by review panels-even though the projects reviewed are operating in the
      same watershed and operated by the same proponent. Project environmental
      assessments must be managed, and coordinated, as part of a larger system of
      impact assessment, if project-by-project assessments are to provide a meaningful
      forum for learning and understanding cumulative change. The paper concludes with
      recommendations for improved project-based assessment practice in support of
      cumulative effects assessment and management.

PMID- 27885388
TI  - Recovery of Forest and Phylogenetic Structure in Abandoned Cocoa Agroforestry in
      the Atlantic Forest of Brazil.
AB  - Cocoa agroforests like the cabrucas of Brazil's Atlantic forest are among the
      agro-ecosystems with greatest potential for biodiversity conservation. Despite a
      global trend for their intensification, cocoa agroforests are also being
      abandoned for socioeconomic reasons especially on marginal sites, because they
      are incorporated in public or private protected areas, or are part of mandatory
      set-asides under Brazilian environmental legislation. However, little is known
      about phylogenetic structure, the processes of forest regeneration after
      abandonment and the conservation value of former cabruca sites. Here we compare
      the vegetation structure and composition of a former cabruca 30-40 years after
      abandonment with a managed cabruca and mature forest in the Atlantic forest
      region of Espirito Santo, Brazil. The forest in the abandoned cabruca had
      recovered a substantial part of its original structure. Abandoned cabruca have a
      higher density (mean +/- CI95 %: 525.0 +/- 40.3 stems per ha), basal area (34.0
      +/- 6.5 m2 per ha) and species richness (148 +/- 11.5 species) than managed
      cabruca (96.0 +/- 17.7; 24.15 +/- 3.9 and 114.5 +/- 16.0, respectively) but no
      significant differences to mature forest in density (581.0 +/- 42.2), basal area
      (29.9.0 +/- 3.3) and species richness (162.6 +/- 15.5 species). Thinning
      (understory removal) changes phylogenetic structure from evenness in mature
      forest to clustering in managed cabruca, but after 30-40 years abandoned cabruca
      had a random phylogenetic structure, probably due to a balance between biotic and
      abiotic filters at this age. We conclude that abandoned cocoa agroforests present
      highly favorable conditions for the regeneration of Atlantic forest and could
      contribute to the formation of an interconnected network of forest habitat in
      this biodiversity hotspot.

PMID- 27885389
TI  - MRI features of perianal fistulas: is there a difference between Crohn's and non
      Crohn's patients?
AB  - PURPOSE: Though perianal fistulas are commonly seen in patients with Crohn's
      disease, they can also be seen in patients without inflammatory bowel disease.
      The purpose of this study was to evaluate MR imaging differences of perianal
      fistulas in patients with and without Crohn's disease. METHODS: Our retrospective
      search from January 2012 to December 2015 of the Radiology database for perianal
      fistula yielded 207 patients. Only patients with dedicated MR fistula protocol
      studies were included, whereas patients with previous anal surgery or
      anastomosis, anorectal tumors, and equivocal findings that could not be
      definitely assessed as a fistula were excluded. The following features were
      assessed: anatomic type of fistula (Parks Classification), luminal origin (hour
      clock position), anal verge distance, signs of acute inflammation, circumference
      of anus involved by inflammation, presence of rectal inflammation. and abscess.
      RESULTS: One hundred and twenty six of 207 patients met inclusion criteria. Of
      these, 96 (76.2%) had Crohn's disease and 30 (23.8%) did not. The most common
      fistulas identified were transphincteric (38.5% of Crohn's and 50% of non
      Crohn's) and intersphincteric (33.3% of Crohn's and 35.4% of non-Crohn's). An
      abscess was associated in 41 cases, 32 (33.3%) in the Crohn's group and 9 (30.0%)
      in the non-Crohn's group. Rectal inflammation was present in 29 patients with
      Crohn's disease (29.2%) and in 2 without Crohn's (6.7%). This finding was
      statistically significant (p = 0.0009). CONCLUSIONS: Our study demonstrates that
      while both groups can have similar MR imaging features, accompanying rectal
      inflammation was more commonly seen in Crohn's disease.

PMID- 27885390
TI  - CT angiography in the setting of suspected acute mesenteric ischemia: prevalence
      of ischemic and alternative diagnoses.
AB  - PURPOSE: The purpose of the study was to determine the prevalence of ischemic and
      alternative diagnoses and the diagnostic accuracy of CT angiography (CTA) in the
      setting of suspected acute mesenteric ischemia (AMI). MATERIAL AND METHODS: We
      included 959 patients undergoing CTA for the evaluation of suspected AMI. The
      final clinical diagnosis was used to determine the prevalence of ischemic and
      alternative diagnoses and to calculate the diagnostic accuracy of CTA. Prevalence
      of diagnoses by age, sex, and admission status was compared using Cochran
      Armitage and chi 2 tests. RESULTS: Prevalence was 18.8% (180/959) for AMI and
      61.2% (587/959) for specific alternative diagnoses. In the remaining 20.0%
      (192/959), no clear clinical diagnosis was established. The most frequent
      alternative diagnoses were small-bowel obstruction (10.4%; 61/587), infectious
      colitis (8.7%; 51/587), pneumonia (6.5%; 38/587), cholecystitis (6.1%; 36/587),
      and diverticulitis (5.6%; 33/587). Prevalence of specific alternative diagnoses
      varied significantly according to both age (p < .013) and admissions status (p <
      0.001). CTA had a sensitivity and specificity for diagnosing AMI of 89.4%/99.5%
      and for alternative diagnoses of 86.7%/96.9%, respectively. CONCLUSION: In the
      setting of suspected AMI, the prevalence of ischemic and alternative diagnoses
      varies significantly by age, sex, and admission status. CTA provides for rapid
      and non-invasive assessment of ischemic and alternative diagnoses with high
      diagnostic accuracy.

PMID- 27885391
TI  - Screening CT colonography reimbursement: triumphs and navigating a path forward.

PMID- 27885392
TI  - Imaging of acute anorectal conditions with CT and MRI.
AB  - Anorectal disorders are a common cause of presentation to the emergency
      department (ED). While the most frequently encountered anorectal conditions, such
      as hemorrhoids and anal fissures, are relatively benign and do not require
      imaging for diagnosis or management, there are multiple potentially life
      threatening anorectal conditions for which imaging is an important component of
      evaluation, diagnosis, and management. Although computed tomography (CT) is the
      most commonly used imaging modality for evaluation of anorectal pathology in the
      ED, magnetic resonance imaging (MRI) has an increasingly important role in the
      detection, characterization and management of specific anorectal conditions. This
      pictorial essay will review the imaging anatomy of the anorectum, summarize
      imaging protocols, and discuss the clinical presentation, imaging appearance, and
      differential diagnosis of anorectal conditions that may present to the emergency
      department, including infectious, inflammatory, malignant and vascular
      conditions.

PMID- 27885393
TI  - Erratum to: Venoarterial extracorporeal membrane oxygenation for cardiac
      arrest/cardiogenic shock.

PMID- 27885394
TI  - Sports-specific differences in postsurgical infections after arthroscopically
      assisted anterior cruciate ligament reconstruction.
AB  - PURPOSE: Post-operative infection after arthroscopically assisted anterior
      cruciate ligament (ACL) reconstruction is a rare but severe complication,
      particularly for young and active patients. It is unclear whether the prevalence
      of knee infection is correlated with the type of sports or the level of
      performance. METHODS: From 2008 to 2012, the internal single-centre ACL registry
      of the FIFA Medical Centre of Excellence Regensburg was retrospectively screened
      for sex, age, time between isolated primary ACL rupture and surgery, surgical
      technique, rate of infection after ACL reconstruction and the type of sports
      practised. RESULTS: In total, 4801 ACL reconstructions had been conducted over 5
      years, 4579 in amateur and 221 in professional athletes. After application of the
      exclusion criteria, 1809 athletes with ACL reconstruction were analysed regarding
      postsurgical infection and the type of sports practised. Professionals and
      amateurs did not significantly differ with regard to infection rates (n.s.) but
      in the timing of ACL repair (p < 0.001). Eleven of 1130 football players had
      developed postsurgical infection after ACL reconstruction (1.0%) in contrast to
      557 skiers and snowboarders without infection (p = 0.02). The timing of ACL
      repair did not differ between the different types of sports (n.s.).
      Staphylococcus aureus and epidermidis were the predominant detected bacteria. All
      patients were hospitalised and successfully treated with arthroscopic lavage and
      antibiotic medication. CONCLUSION: ACL infections showed sports-related
      differences. Athletes practising summer outdoor sports such as football had a
      significantly higher risk of infection after ACL reconstruction than winter
      sports athletes. No difference was found between professional and amateur
      athletes. Relevant prevention strategies for postsurgical ACL infections should
      consider influencing patient factors such as the type of sports activity and
      attendant circumstances. LEVEL OF EVIDENCE: III.

PMID- 27885396
TI  - The Effect of Liming and Sewage Sludge Application on Heavy Metal Speciation in
      Soil.
AB  - The aim of this paper is to assess the effect of liming and low doses of
      municipal sewage sludge (5%, 10%, 15% of the soil mass) on lead, chromium and
      nickel speciation in soil. The 420-day experiment was carried out in laboratory
      conditions. In all the samples lead, chromium and nickel concentration was
      determined with the ICP-AES method, while the content of those metals in
      different fractions was measured with the seven-step Zeien and Brummer method, on
      the 30th and 420th days of the experiment. Sewage sludge doses significantly
      diversified lead, chromium and nickel amounts in the soil. The highest dose of
      sludge caused a significant increase, compared to the control, in the content of
      those metals. In the sludge the dominant forms of metals tested in the experiment
      were lead and chromium bound to organic matter (F4) as well as nickel bound to
      amorphous iron oxides (F5). Liming decreased the mobility of the metals in the
      soil.

PMID- 27885395
TI  - Hip instability treated with arthroscopic capsular plication.
AB  - PURPOSE: Atraumatic microinstability of the hip is felt to be a cause of intra
      articular pathology, particularly tears of the anterior labrum. The purpose of
      this study is to evaluate a consecutive series of patients with atraumatic hip
      microinstability that resulted in anterior labral and cartilage pathology,
      treated with hip arthroscopy and capsular plication without any associated bony
      procedures. METHODS: Thirty-two patients underwent hip arthroscopy and suture
      capsular plication for the treatment of hip instability without concomitant bony
      resections of the acetabulum or proximal femur between November 2009 and November
      2012 and were followed for a minimum of 12 months. Patients were clinically
      evaluated preoperatively and again at 3, 6, 12, 24, and 36 months postoperatively
      with the modified Harris hip score (mHHS) and iHOT score in some patients (as
      this was introduced late in the study). Comparison was made evaluating centre
      edge angle, Tonnis angle, physical examination findings, and demographics on
      outcome. RESULTS: There was significant improvement in the mean mHHS from 67 (SD
      = 8.7) to 97 (SD = 4.7) and iHOT score from 41 (SD = 18.3) to 85 (SD = 10.1) at
      final follow-up. When comparing patients with mild hip dysplasia to patients
      without hip dysplasia, there was no significant difference in clinical outcome at
      any point in follow-up. There was no significant association between patient age,
      duration of preoperative symptoms, previous ipsilateral hip arthroscopy, nature
      of onset of symptoms, centre-edge angle, Tonnis angle, or preoperative physical
      examination findings with clinical outcome at final follow-up. CONCLUSION:
      Isolated arthroscopic suture capsular plication performed for the treatment of
      hip instability resulted in improved patient pain and function at a minimum of 1
      year follow-up.

PMID- 27885397
TI  - Assessment of Indexes for Heavy Metal Contamination in Remote Areas: A Case Study
      in a Pyrenean Forest, Navarra, Spain.
AB  - The objective of the present work was to verify and compare the performance of
      different geochemical indices employed to identify the anthropogenic origin of
      selected heavy metals and other trace elements in soils. To that end, two
      background values, the upper continental crust and the metal content in the bed
      rock, were used and obtained from a forested basin of the western Pyrenees. The
      enrichment factor (EF), geo-accumulation index (Igeo), and contamination factor
      (Cif) were finally evaluated for their ability to determine anthropogenic
      contamination: Results indicate that an in-depth knowledge of the bed rock
      geochemistry and the geological background content is essential to distinguish
      between the natural variability of soils and any anthropogenic contribution of
      heavy metals. Although both EF and Cif show a similar ability to detect soil
      contamination, the latter is proposed as a more appropriate and sensitive marker
      given its ability for finding episodically elevated contamination levels.

PMID- 27885398
TI  - Real-world risk of diabetes with antipsychotic use in older New Zealanders: a
      case-crossover study.
AB  - PURPOSE: The primary aim was to examine and compare the increased risk of
      incident diabetes associated with second-generation antipsychotics (SGAs) and
      first-generation antipsychotics (FGAs), with and without adjusting for potential
      confounding factors. The secondary aim was to recalculate the relative risks of
      diabetes onset using a semi-symmetric bidirectional case-crossover (SSBC) design
      to adjust for time-trend bias. METHOD: Prescription records (2005-2015) of
      antipsychotics were sourced from New Zealand Pharmaceutical Collections. The
      first-time diabetes diagnosis was extracted from the National Minimal Dataset.
      Relative risks (RRs) of diabetes onset were calculated using conditional logistic
      regression. Time-trend bias was corrected by recalculating the RR using a SSBC
      design. RESULTS: Among 645 individuals, the risk of diabetes onset is higher in
      SGA users (ARR = 8.72, 95% CI = [5.57, 13.67]) compared to FGA users (ARR = 5.68,
      95% CI = [3.43, 9.39]). The increased risk of diabetes onset associated with
      quetiapine is higher (ARR = 7.47, 95% CI = [4.10, 13.62]), compared to
      haloperidol (ARR = 5.05, 95% CI = [2.91, 8.75]). However, the increased risk of
      diabetes onset associated with olanzapine (ARR = 2.27, 95% CI = [0.86, 5.98]) is
      insignificant after adjusting for concomitant use of effect modifiers and other
      antipsychotic drugs. CONCLUSION: The results support that the magnitude of the
      risk of diabetes is higher with SGA use compared with FGA use, and the risk is
      higher when co-prescribed. Confounding by indication and time-varying confounders
      such as body mass index could bias the risk of onset of diabetes. Marginal
      structural models could provide more precise estimates of the risk of onset of
      diabetes following exposure to antipsychotics.

PMID- 27885399
TI  - Absolute oral bioavailability of selexipag, a novel oral prostacyclin IP receptor
      agonist.
AB  - PURPOSE: The aim of this single-center, open-label study was to assess the
      absolute bioavailability of an oral (tablet) versus intravenous (i.v.)
      formulation of selexipag in healthy subjects. METHODS: A pilot phase in three
      healthy male subjects, which preceded the main study, consisted of a single 20
      minute i.v. infusion of 50 MUg selexipag. Its objectives were to ensure the
      safety of the i.v. formulation and to select the i.v. dose for the main study.
      The main study had a randomized, two-way crossover design in 16 healthy male
      subjects. Subjects received a single oral dose of 400 MUg selexipag and a single
      80-minute i.v. infusion of 200 MUg selexipag. RESULTS: Three subjects in the
      pilot and 15 in the main phase completed the study as planned, whereas one
      subject of the main study withdrew the consent. A geometric mean total body
      clearance (95% confidence interval (CI)) of 17.9 L/h (15.0-21.5) and a volume of
      distribution of 11.7 L (10.6-13.0) were determined. The absolute oral
      bioavailability of selexipag (90% CI) was 49.4% (42.6-57.2). Selexipag was well
      tolerated; no adverse event (AE) occurred during the pilot phase, and the main
      observed AEs were headache, nausea, and vomiting. CONCLUSION: A single i.v.
      administration of selexipag in healthy subjects was safe and well-tolerated. The
      bioavailability of selexipag after oral administration is approximately 50%.

PMID- 27885400
TI  - Influences on antidepressant prescribing trends in the UK: 1995-2011.
AB  - PURPOSE: The number of antidepressants prescribed in the UK has been increasing
      over the last 25 years; however, the reasons for this are not clear. This study
      examined trends in antidepressant prescribing in the UK between 1995 and 2011
      according to age, sex, and drug class, and investigated reasons for the increase
      in prescribing over this period. METHODS: This is a retrospective analysis of
      antidepressant prescribing data from the Clinical Practice Research Datalink: a
      large, anonymised, primary care database in the UK. The dataset used in this
      study included 138 practices, at which a total of 1,524,201 eligible patients
      were registered across the 17-year period. The proportion of patients who
      received at least one antidepressant prescription and the number of patients who
      started a course of antidepressants were calculated for each year of the study.
      We used person years (PY) at risk as the denominator. The duration of treatment
      for those starting antidepressants was also examined. RESULTS: 23% of patients
      were prescribed an antidepressant on at least one occasion over the 17-year study
      period. Antidepressant prescriptions rose from 61.9 per 1000 PY in 1995 to 129.9
      per 1000 PY in 2011. This was largely driven by an increase in prescribing of
      selective serotonin reuptake inhibitors and 'other' antidepressants. In contrast,
      incidence rates of those starting antidepressants remained relatively stable
      (1995: 21.3 per 1000 PY; 2011: 17.9 per 1000 PY). The duration of treatment
      increased with later starting years, with an increasing proportion of long-term
      use, and decrease in short-term use. CONCLUSION: The increase in antidepressant
      prescribing over the study period appears to be driven by an increase in long
      term use of these medications.

PMID- 27885401
TI  - [Cutaneous side effects of targeted cancer drugs].
AB  - In the past decades many new drugs were approved for the treatment of cancer and
      have been established as essential parts of various therapeutic regimens. In
      particular targeted therapies and immune checkpoint inhibitors that aim at
      specific carcinogenic signaling pathways or modulate the tumor-immune response
      have revolutionized cancer therapy. Despite their targeted actions, these drugs
      may lead to diverse adverse reactions. In particular, cutaneous toxicities
      represent a serious threat to patients' quality of life and may lead to dose
      reduction or therapy cessation. In most cases, basic management is performed by
      the treating oncologist. Nevertheless, more severe reactions may require the
      expertise of a dermatologist. In this review, we present specific cutaneous
      adverse reactions of new drug classes such as epidermal growth factor receptor
      inhibitors (EGFR-I), multikinase inhibitors (MKI), BRAF inhibitors, MEK
      inhibitors, and immune checkpoint inhibitors (anti-PD1-, anti-CTLA4-antibodies).
      Furthermore, we give recommendations concerning the prevention and management of
      respective cutaneous reactions.

PMID- 27885402
TI  - [Retention of contrast media in the history of radiology : Sequelae of the former
      use of thorotrast and new challenges].
AB  - Detection of gadolinium deposits in patients who have repeatedly been
      administered intravenous gadolinium chelates have given rise to concern regarding
      the long-term safety of magnetic resonance imaging (MRI) contrast media.
      Nevertheless, negative long-term clinical effects have not yet been observed. In
      some publications parallels have been drawn to the sequelae of thorotrast that
      was formerly used for arterial angiography. In this article the history of
      thorotrast use is briefly described and in particular why, despite warnings, this
      substance was used frequently and worldwide. A brief summary of the results of
      the German Thorotrast Study revealed that high excess rates were only observed
      for primary malignant liver tumors after a 15-year or longer latency period and
      to a lesser degree of leukemias, as well as for severe local complications due to
      paravascular injections, particularly in the neck region. Based on this
      historical review, we will venture to take stock of the outcome from the "success
      story" of this contrast agent.

PMID- 27885403
TI  - [When a name becomes a unit: Antoine Henri Becquerel].

PMID- 27885404
TI  - [Health examination of asylum seekers: A nationwide analysis of state policies in
      Germany : S 62 of the asylum law].
AB  - BACKGROUND: A health examination of newly arrived asylum seekers, aimed at
      detecting infectious diseases and preventing disease outbreaks in accommodation
      facilities, is mandated by national law in all German states. Due to the
      decentralized German federal system, different state policies are in place and
      lead to substantial variation in the content and implementation of the health
      examination. OBJECTIVES: To compare health examination policies in the 16 German
      states with a focus on conducted tests, preventive measures and the general
      procedure. METHODS: A comparative content analysis of policy documents addressing
      the health examination was conducted. Relevant documents were identified through
      a nationwide search (conducted June-October 2015) through public sources,
      inquiries at responsible authorities and interviews with representatives of
      public health services. RESULTS: In the study period, relevant policy documents
      for 13 states were identified, of which eight were administrative decrees of the
      responsible state ministries. Policies differed strongly with respect to the
      content of the health examination and the selection of compulsory screening
      measures. We identified three main groups: (A) states with compulsory screening
      limited to measures enshrined in federal law, (B) states with extended
      tuberculosis screening for children and pregnant women, and (C) states with
      extended mandatory screening measures for further infectious diseases beyond
      tuberculosis. Considerable differences were also found with regard to the
      implementation of the examinations, and the purchasing and re-imbursement
      policies. CONCLUSIONS: The stark heterogeneity in health examination policies
      between the states cannot be rationally explained from a public health
      perspective. The indication for certain measures remains unclear. A broad
      discussion of the medical necessity of screening tests, combined with further
      systematic analyses, is necessary in order to develop nationwide evidence-based
      recommendations and decision-making tools for the conduct of health examinations
      of asylum seekers.

PMID- 27885405
TI  - Executive control and working memory are involved in sub-second repetitive motor
      timing.
AB  - The nature of the relationship between timing and cognition remains poorly
      understood. Cognitive control is known to be involved in discrete timing tasks
      involving durations above 1 s, but has not yet been demonstrated for repetitive
      motor timing below 1 s. We examined the latter in two continuation tapping
      experiments, by varying the cognitive load in a concurrent task. In Experiment 1,
      participants repeated a fixed three finger sequence (low executive load) or a
      pseudorandom sequence (high load) with either 524-, 733-, 1024- or 1431-ms inter
      onset intervals (IOIs). High load increased timing variability for 524 and 733-ms
      IOIs but not for the longer IOIs. Experiment 2 attempted to replicate this
      finding for a concurrent memory task. Participants retained three letters (low
      working memory load) or seven letters (high load) while producing intervals (524-
      and 733-ms IOIs) with a drum stick. High load increased timing variability for
      both IOIs. Taken together, the experiments demonstrate that cognitive control
      processes influence sub-second repetitive motor timing.

PMID- 27885406
TI  - Abnormal connectivity in the sensorimotor network predicts attention deficits in
      traumatic brain injury.
AB  - The aim of this study was to explore modifications of functional connectivity in
      multiple resting-state networks (RSNs) after moderate to severe traumatic brain
      injury (TBI) and evaluate the relationship between functional connectivity
      patterns and cognitive abnormalities. Forty-three moderate/severe TBI patients
      and 34 healthy controls (HC) underwent resting-state fMRI. Group ICA was applied
      to identify RSNs. Between-subject analysis was performed using dual regression.
      Multiple linear regressions were used to investigate the relationship between
      abnormal connectivity strength and neuropsychological outcome. Forty (93%) TBI
      patients showed moderate disability, while 2 (5%) and 1 (2%) upper severe
      disability and low good recovery, respectively. TBI patients performed worse than
      HC on the domains attention and language. We found increased connectivity in
      sensorimotor, visual, default mode (DMN), executive, and cerebellar RSNs after
      TBI. We demonstrated an effect of connectivity in the sensorimotor RSN on
      attention (p < 10-3) and a trend towards a significant effect of the DMN
      connectivity on attention (p = 0.058). A group-by-network interaction on
      attention was found in the sensorimotor network (p = 0.002). In TBI, attention
      was positively related to abnormal connectivity within the sensorimotor RSN,
      while in HC this relation was negative. Our results show altered patterns of
      functional connectivity after TBI. Attention impairments in TBI were associated
      with increased connectivity in the sensorimotor network. Further research is
      needed to test whether attention in TBI patients is directly affected by changes
      in functional connectivity in the sensorimotor network or whether the effect is
      actually driven by changes in the DMN.

PMID- 27885407
TI  - Effect of metal sulfide pulp density on gene expression of electron transporters
      in Acidithiobacillus sp. FJ2.
AB  - In Acidithiobacillus ferrooxidans, one of the most important bioleaching
      bacterial species, the proteins encoded by the rus operon are involved in the
      electron transfer from Fe2+ to O2. To obtain further knowledge about the
      mechanism(s) involved in the adaptive responses of the bacteria to growth on the
      different uranium ore pulp densities, we analyzed the expression of the four
      genes from the rus operon by real-time PCR, when Acidithiobacillus sp. FJ2 was
      grown in the presence of different uranium concentrations. The uranium
      bioleaching results showed the inhibitory effects of the metal pulp densities on
      the oxidation activity of the bacteria which can affect Eh, pH, Fe oxidation and
      uranium extractions. Gene expression analysis indicated that Acidithiobacillus
      sp. FJ2 tries to survive in the stress with increasing in the expression levels
      of cyc2, cyc1, rus and coxB, but the metal toxicity has a negative effect on the
      gene expression in different pulp densities. These results indicated that
      Acidithiobacillus sp. FJ2 could leach the uranium even in high pulp density (50%)
      by modulation in rus operon gene responses.

PMID- 27885408
TI  - Erratum to: A novel CYP24A1 genotype associated to a clinical picture of
      hypercalcemia, nephrolithiasis and low bone mass.

PMID- 27885409
TI  - [Simultaneous surgical treatment of the long head of the biceps tendon during
      operative treatment of proximal humeral fractures].
AB  - BACKGROUND: Pathologic conditions of the long biceps tendon can be found within
      treatment of proximal humeral fractures or as a source of pain after surgery.
      However, simultaneous surgical treatment at the index surgical intervention is so
      far not well established. The purpose of this study is to evaluate the results of
      a simultaneous biceps treatment during plate osteosynthesis of proximal humeral
      fractures. MATERIALS AND METHODS: Twenty-seven patients were included into this
      study. In 14 patients (high cosmetic and functional shoulder demand) a biceps
      tenodesis (LHB-TD) was carried out (7 women, 7 men; o57 years). In 13 patients
      (12 women, 1 man; o72 years) a biceps tenotomy (LHB-TT) was performed. In
      addition to the range of motion (ROM), the Constant score and the LHB score were
      evaluated. RESULTS: All 27 patients were investigated after a mean follow-up of
      25 months (range: 18-32 months). The ROM did not reveal any significant
      differences in either group. The Constant score was significantly decreased
      compared to the non-affected side (CS) without differences between the groups
      (LBS-TT 77 +/- 9 vs. LBS-TD 77 +/- 14; LBS-TT (CS) 82 +/- 4 vs. LBS-TD (CS) 87 +/
      4). The LHB score showed excellent results for both groups without significant
      differences (LBS-TT 98 +/- 3 vs. LBS-TD 93 +/- 10). In one patient of each group,
      an examiner-dependent upper arm deformity was detected. No patient complained of
      a subjective cosmetic deformity. CONCLUSION: The simultaneous surgical treatment
      of the LHB during plate osteosynthesis of proximal humeral fractures shows good
      clinical and cosmetic results. In a preselected patient population (cosmetic and
      functional demand) the kind of treatment (LHB tenotomy or LHB tenodesis) is
      indifferent.

PMID- 27885410
TI  - Is osteoporosis a predictor for future sarcopenia or vice versa? Four-year
      observations between the second and third ROAD study surveys.
AB  - : In a 4-year follow-up study that enrolled 1099 subjects aged >=60 years,
      sarcopenia prevalence was estimated at 8.2%. Moreover, the presence of
      osteoporosis was significantly associated with short-term sarcopenia occurrence,
      but the reciprocal relationship was not observed, suggesting that osteoporosis
      would increase the risk of osteoporotic fracture and sarcopenia occurrence.
      INTRODUCTION: The present 4-year follow-up study was performed to clarify the
      prevalence, incidence, and relationships between sarcopenia (SP) and osteoporosis
      (OP) in older Japanese men and women. METHODS: We enrolled 1099 participants
      (aged, >=60 years; 377 men) from the second survey of the Research on
      Osteoarthritis/Osteoporosis against Disability (ROAD) study (2008-2010) and
      followed them up for 4 years. Handgrip strength, gait speed, skeletal muscle
      mass, and bone mineral density were assessed. SP was defined according to the
      Asian Working Group for Sarcopenia. OP was defined based on the World Health
      Organization criteria. RESULTS: SP prevalence was 8.2% (men, 8.5%; women, 8.0%)
      in the second survey. In those with SP, 57.8% (21.9%; 77.6%) had OP at the lumbar
      spine L2-4 and/or femoral neck. SP cumulative incidence was 2.0%/year (2.2%/year;
      1.9%/year). Multivariate regression analysis revealed that OP was significantly
      associated with SP occurrence within 4 years (odds ratio, 2.99; 95% confidence
      interval, 1.46-6.12; p < 0.01), but the reciprocal relationship was not
      significantly observed (2.11; 0.59-7.59; p = 0.25). CONCLUSIONS: OP might raise
      the short-term risk of SP incidence. Therefore, OP would not only increase the
      risk for osteoporotic fracture but may also increase the risk for SP occurrence.

PMID- 27885412
TI  - Kynurenic acid and alcohol and cocaine dependence: novel effects and multiple
      mechanisms?

PMID- 27885411
TI  - Scopolamine disrupts place navigation in rats and humans: a translational
      validation of the Hidden Goal Task in the Morris water maze and a real maze for
      humans.
AB  - RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD)
      requires valid paradigms for testing their efficacy and sensitive tests validated
      in translational research. OBJECTIVES: We present validation of a place
      navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM),
      in comparable animal and human protocols. METHODS: We used scopolamine to model
      cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic
      medication for AD, to assess its potential reversible effect on this scopolamine
      induced cognitive dysfunction. We tested the effects of scopolamine and the
      combination of scopolamine and donepezil on place navigation and compared their
      effects in human and rat versions of the HGT. Place navigation testing consisted
      of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans
      or 1, 2.5, and 5 h in rats. RESULTS: Scopolamine worsened performance in both
      animals and humans. In the animal experiment, co-administration of donepezil
      alleviated the negative effect of scopolamine. In the human experiment, subjects
      co-administered with scopolamine and donepezil performed similarly to subjects on
      placebo and scopolamine, indicating a partial ameliorative effect of donepezil.
      CONCLUSIONS: In the task based on the MWM, scopolamine impaired place navigation,
      while co-administration of donepezil alleviated this effect in comparable animal
      and human protocols. Using scopolamine and donepezil to challenge place
      navigation testing can be studied concurrently in animals and humans and may be a
      valid and reliable model for translational research, as well as for preclinical
      and clinical phases of drug trials.

PMID- 27885414
TI  - Clinical implementation of an emergency department coronary computed tomographic
      angiography protocol for triage of patients with suspected acute coronary
      syndrome.
AB  - OBJECTIVES: To evaluate the efficiency and safety of emergency department (ED)
      coronary computed tomography angiography (CTA) during a 3-year clinical
      experience. METHODS: Single-center registry of coronary CTA in consecutive ED
      patients with suspicion of acute coronary syndrome (ACS). The primary outcome was
      efficiency of coronary CTA defined as the length of hospitalization. Secondary
      endpoints of safety were defined as the rate of downstream testing, normalcy
      rates of invasive coronary angiography (ICA), absence of missed ACS, and major
      adverse cardiac events (MACE) during follow-up, and index radiation exposure.
      RESULTS: One thousand twenty two consecutive patients were referred for clinical
      coronary CTA with suspicion of ACS. Overall, median time to discharge home was
      10.5 (5.7-24.1) hours. Patient disposition was 42.7 % direct discharge from the
      ED, 43.2 % discharge from emergency unit, and 14.1 % hospital admission. ACS rate
      during index hospitalization was 9.1 %. One hundred ninety two patients underwent
      additional diagnostic imaging and 77 underwent ICA. The positive predictive value
      of CTA compared to ICA was 78.9 % (95 %-CI 68.1-87.5 %). Median CT radiation
      exposure was 4.0 (2.5-5.8) mSv. No ACS was missed; MACE at follow-up after
      negative CTA was 0.2 %. CONCLUSIONS: Coronary CTA in an experienced tertiary care
      setting allows for efficient and safe management of patients with suspicion for
      ACS. KEY POINTS: * ED Coronary CTA using advanced systems is associated with low
      radiation exposure. * Negative coronary CTA is associated with low rates of MACE.
      * CTA in ED patients enables short median time to discharge home. * CTA strategy
      is characterized by few downstream tests including unnecessary ICA.

PMID- 27885413
TI  - Novel brewing yeast hybrids: creation and application.
AB  - The natural interspecies Saccharomyces cerevisiae * Saccharomyces eubayanus
      hybrid yeast is responsible for global lager beer production and is one of the
      most important industrial microorganisms. Its success in the lager brewing
      environment is due to a combination of traits not commonly found in pure yeast
      species, principally low-temperature tolerance, and maltotriose utilization.
      Parental transgression is typical of hybrid organisms and has been exploited
      previously for, e.g., the production of wine yeast with beneficial properties.
      The parental strain S. eubayanus has only been discovered recently and newly
      created lager yeast strains have not yet been applied industrially. A number of
      reports attest to the feasibility of this approach and artificially created
      hybrids are likely to have a significant impact on the future of lager brewing.
      De novo S. cerevisiae * S. eubayanus hybrids outperform their parent strains in a
      number of respects, including, but not restricted to, fermentation rate, sugar
      utilization, stress tolerance, and aroma formation. Hybrid genome function and
      stability, as well as different techniques for generating hybrids and their
      relative merits are discussed. Hybridization not only offers the possibility of
      generating novel non-GM brewing yeast strains with unique properties, but is
      expected to aid in unraveling the complex evolutionary history of industrial
      lager yeast.

PMID- 27885416
TI  - Favorable renal outcome in Japanese children with ANCA-associated pauci-immune
      glomerulonephritis: impact of urine screening program.

PMID- 27885415
TI  - Resting heart rate and risk of metabolic syndrome in adults: a dose-response meta
      analysis of observational studies.
AB  - The magnitude of the risk of metabolic syndrome (MetS) with increased resting
      heart rate (RHR) has been inconsistently reported in some observational studies,
      and whether a dose-response relationship exists between RHR and MetS is unclear.
      We performed a meta-analysis including dose-response analysis to quantitatively
      evaluate this association in adults. We searched PubMed, Web of Knowledge, China
      National Knowledge Infrastructure, and WanFang databases for articles published
      up to April 2, 2016. A random-effects model was used to pool relative risks (RRs)
      and 95% confidence intervals (CIs); restricted cubic spline function was used to
      assess the dose-response relationship. Seven prospective cohort studies and 10
      cross-sectional studies with a total of 169,786 participants were included. The
      pooled RR was 2.10 (95% CI 1.80-2.46, I 2 = 79.8%, n = 13) for the highest versus
      reference RHR category and 1.28 (95% CI 1.23-1.34, I 2 = 87.7%, n = 15) for each
      10 beats per minute (bpm) increment in RHR. We found no evidence of a nonlinear
      dose-response association between RHR and MetS (P nonlinearity = 0.201). The
      relationship was consistent in most subgroup analyses and robust on sensitivity
      analysis. No significant publication bias was observed. This meta-analysis
      suggests that risk of MetS may be increased with elevated RHR.

PMID- 27885417
TI  - Favorable renal outcome in Japanese children with ANCA-associated pauci-immune
      glomerulonephritis: authors' response to comments.

PMID- 27885419
TI  - Ketoconazole inhibits Malassezia furfur morphogenesis in vitro under
      filamentation optimized conditions.
AB  - Malassezia furfur, a constituent of the normal human skin flora, is an
      etiological agent of pityriasis versicolor, which represents one of the most
      common human skin diseases. Under certain conditions, both exogenous and
      endogenous, the fungus can transition from a yeast form to a pathogenic mycelial
      form. To develop a standardized medium for reproducible production of the
      mycelial form of M. furfur to develop and optimize susceptibility testing for
      this pathogen, we examined and characterized variables, including kojic acid and
      glycine concentration, agar percentage, and pH, to generate a chemically defined
      minimal medium on which specific inoculums of M. furfur generated the most robust
      filamentation. Next, we examined the capacity of ketoconazole to inhibit the
      formation of M. furfur mycelial form. Both low and high, 0.01, 0.05 and 0.1 ug/ml
      concentrations of ketoconazole significantly inhibited filamentation at 11.9,
      54.5 and 86.7%, respectively. Although ketoconazole can have a direct antifungal
      effect on both M. furfur yeast and mycelial cells, ketoconazole also has a
      dramatic impact on suppressing morphogenesis. Since mycelia typified the
      pathogenic form of Malassezia infection, the capacity of ketoconazole to block
      morphogenesis may represent an additional important effect of the antifungal.

PMID- 27885420
TI  - Erratum to: Effectiveness of adalimumab for the treatment of ulcerative colitis
      in clinical practice: comparison between anti-tumour necrosis factor-naive and
      non-naive patients.

PMID- 27885418
TI  - Phylogenetic and functional traits of ectomycorrhizal assemblages in top soil
      from different biogeographic regions and forest types.
AB  - Ectomycorrhizal (EM) fungal taxonomic, phylogenetic, and trait diversity
      (exploration types) were analyzed in beech and conifer forests along a north-to
      south gradient in three biogeographic regions in Germany. The taxonomic community
      structures of the ectomycorrhizal assemblages in top soil were influenced by
      stand density and forest type, by biogeographic environmental factors (soil
      physical properties, temperature, and precipitation), and by nitrogen forms
      (amino acids, ammonium, and nitrate). While alpha-diversity did not differ
      between forest types, beta-diversity increased, leading to higher gamma-diversity
      on the landscape level when both forest types were present. The highest taxonomic
      diversity of EM was found in forests in cool, moist climate on clay and silty
      soils and the lowest in the forests in warm, dry climate on sandy soils. In the
      region with higher taxonomic diversity, phylogenetic clustering was found, but
      not trait clustering. In the warm region, trait clustering occurred despite
      neutral phylogenetic effects. These results suggest that different forest types
      and favorable environmental conditions in forests promote high EM species
      richness in top soil presumably with both high functional diversity and
      phylogenetic redundancy, while stressful environmental conditions lead to lower
      species richness and functional redundancy.

PMID- 27885421
TI  - Role of vernalization-mediated demethylation in the floral transition of Brassica
      rapa.
AB  - MAIN CONCLUSION: Vernalization-mediated demethylation of BrCKA2 (casein kinase II
      alpha-subunit) and BrCKB4 (casein kinase II beta-subunit) shorten the period of
      the clock gene BrCCA1 (circadian clock associated 1) in Brassica rapa.
      Photoperiod and vernalization are two environmental cues involved in the
      regulation of floral transition, but the ways in which they interact remain
      unclear. DNA methylation is one of the main mechanisms involved in controlling
      the functional state of chromatin and gene expression in response to
      environmental signals. To study the interaction between photoperiod and
      vernalization in floral transition, we carried out a comparative genomic analysis
      of genome-wide DNA methylation profiles in normal (CK) and vernalized (CA) leaves
      from Brassica rapa using methylated-DNA immunoprecipitation sequencing (MeDIP
      seq). Two subunits of casein kinase II (CK2), BrCKA2 (catalytic alpha-subunit of
      CK2) and BrCKB4 (regulatory beta-subunit of CK2), exhibited gradual DNA
      demethylation and increased expression in vernalized B. rapa. DNA methylation
      defective plants demonstrated the causal link between DNA demethylation changes
      and changes in gene expression. Virus-induced gene silencing (VIGS) of BrCKA2 and
      BrCKB4 in B. rapa resulted in no change to the period of BrCCA1 (circadian clock
      associated 1) and a 1-week late flowering time. Finally, we demonstrated that
      increased levels of BrCKA2 and BrCKB4 in vernalized B. rapa confer elevated CK2
      activity, resulting in a shortened period of the clock gene BrCCA1, which plays
      an important role in perceiving photoperiod in plants. Thus, our results suggest
      that there is a direct interaction between photoperiod and vernalization through
      DNA methylation mechanisms.

PMID- 27885422
TI  - CD44 induces FOXP3 expression and is related with favorable outcome in breast
      carcinoma.
AB  - We studied the relationship between CD44 and Forkhead box P3 (FOXP3) gene
      expression in cell lines and breast carcinomas and their association with
      clinicopathological variables and patient outcome. We assessed messenger RNA
      (mRNA) expression of CD44 and FOXP3 by quantitative real-time PCR and determined
      the number of FOXP3+ Tregs by immunohistochemistry in 264 breast cancer
      specimens. CD44 was stimulated with hyaluronan treatment, and the accompanying
      changes in FOXP3 mRNA expression in breast cancer cell lines representing breast
      cancer subtype were assessed. We found that lower CD44 expression correlated with
      the presence of necrosis, lymph-vascular invasion, grade 3 tumors, and aggressive
      phenotype (HER2 and basal-like). FOXP3 mRNA correlated positively with CD44 mRNA
      expression and Treg content. Moreover, stimulation of CD44 expression by
      hyaluronan in cell lines increased FOXP3 expression, which supports that their
      regulation is associated. Survival analysis revealed that low CD44 expression is
      associated with higher frequency of recurrence. Our findings indicate that CD44
      has a regulatory role in FOXP3 expression and is associated with good prognostic
      factors in breast cancer.

PMID- 27885424
TI  - Editorial.

PMID- 27885427
TI  - [The Homburger Curriculum as a model for medical resident education for
      ophthalmologists at Saarland University Medical Center].
AB  - BACKGROUND: The Homburger Curriculum was introduced in 2012 to enhance the
      medical resident education and professional satisfaction. At the same time
      different steps were taken to encourage applications of eligible candidates.
      METHODS: To address candidates, the Homburger Curriculum is presented on the
      department's website and a short-term hospitation was introduced. The curriculum
      has been divided into time slots of 4 months throughout the 5 years of residency.
      In addition, a booklet of documented evidence of the rotations and a Resident's
      Compendium were introduced. Internal and external teaching programs, additional
      research projects and involvement of the residents in the organization of their
      curriculum were introduced. The paper describes the rationale behind the new
      structure of the curriculum and its practical outcomes for the department (e. g.
      a regular standby resident to fill in unexpected gaps). RESULTS: It is discussed
      in detail which steps were easy to implement and which steps were more difficult
      to introduce. After consolidation of the numerous steps, the number of resigning
      residents dropped significantly and the number of applicants increased.
      CONCLUSIONS: The new rotation schedule guarantees every young resident to be able
      to work at each work area of the Department of Ophthalmology. External training
      courses can be planned suitable to his/her rotations. An "internal competition"
      for popular rotations is no longer necessary. Clear organization and transparency
      in all areas provide good interpersonal climate in which much work still has to
      be done, but by motivated and satisfied residents.

PMID- 27885423
TI  - Publication trends in cachexia and sarcopenia in elderly heart failure patients.
AB  - The loss of skeletal mass - sarcopenia and cachexia - is considered to be a major
      contributor to morbidity and mortality in chronic heart failure (CHF).
      Unfortunately, sarcopenia is generally considered to be a geriatric syndrome, but
      not necessarily seen as a comorbidity in CHF, even though it has a wide range of
      adverse health outcomes. While there were 15,574 publication with the title word
      "heart failure" in PubMed in the 5-year period from 1 June 2011 to 31 May 2016,
      only 22 or 71 publications were found with the search combination "sarcopenia" or
      "cachexia" (title word) and "heart failure" (all fields), respectively. This
      shows very clearly that loss of muscle quality and function due to heart failure
      is still an underappreciated problem in the medical field.

PMID- 27885425
TI  - Intrathecal morphine versus intravenous opioid administration to impact
      postoperative analgesia in hepato-pancreatic surgery: a randomized controlled
      trial.
AB  - PURPOSE: Inadequate analgesia following abdominal surgery may affect outcome.
      Data in patients undergoing liver surgery suggested that postoperative
      coagulopathy might delay epidural catheter removal. Thus, alternative analgesic
      techniques should be evaluated. METHODS: We compared the analgesic efficacy of
      intraoperative intrathecal morphine [single injection 4 ug/kg before skin
      incision (ITM group, n = 23)] to intravenous opioids [iv remifentanil infusion
      during surgery followed by i.v. bolus of morphine, 0.15 mg/kg before the end of
      surgery (IVO group, n = 26)]. Forty-nine adult patients undergoing elective open
      resection of liver or pancreas lesions in the Tel Aviv Medical Center were
      randomized into the two analgesic protocols. Postoperatively both groups received
      i.v. morphine via a patient-controlled analgesia pump. Follow-up was till the 3rd
      postoperative day (POD). RESULTS: There was no significant difference in
      demographics and intraoperative data between groups. The primary outcome, pain
      scores on movement, was significantly worse in the IVO group when compared with
      the ITM group at various time points till POD3. In the secondary outcomes - need
      for rescue drugs - the IVO group required significantly more rescue morphine
      boluses. Complication related to the analgesia and recovery parameters were
      similar between groups. CONCLUSIONS: The findings suggest that a single dose of
      ITM before hepatic/pancreatic surgery may offer better postoperative pain control
      than i.v. opioid administration during surgery. This beneficial effect is
      maintained throughout the first three PODs and is not associated with a higher
      complication rate; neither did it influence recovery parameters. ITM provides an
      appropriate alternative to i.v. morphine during major abdominal surgery.

PMID- 27885426
TI  - Prospective cohort study assessing chronic pain in patients following minor
      surgery for breast cancer.
AB  - PURPOSE: Pain after tumorectomy and sentinel lymph node dissection is poorly
      reported in the literature. We carried out a prospective survey aimed at
      assessing pain three months after such minor surgery for breast cancer. METHODS:
      The study was approved by the local ethics committee. Most surgeries followed a
      standard protocol involving general anesthesia with no regional analgesia
      technique, laryngeal mask, sufentanil and propofol for induction, and multimodal
      analgesia during the postoperative period. Three months after the surgery, a
      questionnaire was sent to the patients with a pre-stamped envelope for return.
      The questions probed responses required to calculate a Brief Pain Inventory score
      and modified neuropathic pain score (DN3). RESULTS: Over a 5-month period, 150
      patients (aged 60 (11) years, body mass index of 25 (6) kg/m2) were included in
      the final analysis. In the recovery room, 43% of patients required morphine at a
      mean dose of 5.2 (1.8) mg. Three months post surgery, 60 patients (40%) reported
      persistent pain for which 62% took analgesic drugs. We found no risk factor
      associated with this persistent pain among our studied population. Neuropathic
      pain was noted in 61% of patients who reported persistent pain primarily
      associated with periareolar incision. CONCLUSIONS: Pain persisted up to three
      months after minor surgery for breast cancer in 40% of patients with mostly a
      neuropathic component (61%).

PMID- 27885429
TI  - Defect width: the prognostic index for vaginal repair of cesarean section
      diverticula.
AB  - PURPOSE: To evaluate the clinical parameter associated with cesarean section
      diverticula anatomic healing via vaginal repair management. METHODS:
      Observational cohort study. From Jul 2014 to Dec 2015, 143 women with CSD
      underwent vaginal repair surgery in Shanghai First Maternity and Infant Hospital,
      and 137(95.80%) were diagnosed using both transvaginal ultrasound and MRI. A
      total of 124 patients (86.71%) who were followed-up for more than 6 months after
      surgery were enrolled in this study. Excision and suture of CSD was performed
      through the vaginal approach. The defect sizes of the width, length, depth and
      TRM before or after repair were evaluated. RESULTS: The mean preoperative
      duration of menstruation was 14.47 +/- 3.30 days and the thickness of the
      remaining muscular layer was 2.65 +/- 1.13 mm before surgery. The study revealed
      that the healing effects of CSD repair stabilized 3 months after surgery. At the
      median follow-up time (11.28 months), CSD disappeared after surgery in 64.52% of
      patients (80/124), and 60.0% of patients (48/80) reached <=7 days of
      menstruation. Meanwhile, for 35.48% of patients (44/124), CSD persisted at the
      median follow-up after surgery, and 31.82% (14/44) of these patients reached <=7
      days of menstruation(P < 0.05). TRM at a median follow-up time after vaginal
      repair >7.88 mm, 92.11% (70/76) of CSD disappeared. Moreover, when preoperative
      CSD width <=18.85 mm indicates that only 18.75% (12/64) of patients will present
      with CSD after vaginal repair, as determined by MRI (95% CI 0.515-0.737).
      CONCLUSION: The defect width of the preoperative CSD was the prognostic index of
      CSD anatomical repair effect. When the preoperative CSD width >18.85 mm, we
      should pay more attention to the edge of the defect during vaginal repairing.

PMID- 27885428
TI  - Normative biometry of the fetal brain using magnetic resonance imaging.
AB  - The fetal brain shows accelerated growth in the latter half of gestation, and
      these changes can be captured by 2D and 3D biometry measurements. The aim of this
      study was to quantify brain growth in normal fetuses using Magnetic Resonance
      Imaging (MRI) and to produce reference biometry data and a freely available
      centile calculator ( https://www.developingbrain.co.uk/fetalcentiles/ ). A total
      of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21-38
      gestational weeks) were included in this study. 2D and 3D biometric parameters
      were measured from slice-to-volume reconstructed images, including 3D
      measurements of supratentorial brain tissue, lateral ventricles, cortex,
      cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal
      diameter and fronto-occipital length, skull biparietal diameter and
      occipitofrontal diameter, head circumference, transverse cerebellar diameter,
      extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and
      area. Centiles were constructed for each measurement. All participants were
      invited for developmental follow-up. All 2D and 3D measurements, except for
      atrial diameter, showed a significant positive correlation with gestational age.
      There was a sex effect on left and total lateral ventricular volumes and the
      degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile
      calculator were produced. Developmental follow-up was available for 73.1% of
      cases [mean chronological age 27.4 (+/-10.2) months]. We present normative
      reference charts for fetal brain MRI biometry at 21-38 gestational weeks.
      Developing growth trajectories will aid in the better understanding of normal
      fetal brain growth and subsequently of deviations from typical development in
      high-risk pregnancies or following premature delivery.

PMID- 27885430
TI  - Blood species discrimination using proton nuclear magnetic resonance
      spectroscopy.
AB  - Blood species identification is an important challenge in forensic science.
      Conventional methods used for blood species analysis are destructive and
      associated with time-consuming sample preparation steps. Nuclear magnetic
      resonance (NMR) spectroscopy is known for its nondestructive properties and fast
      results. This research study presents a proton (1H) NMR method to discriminate
      blood species including human, cat, dog, elephant, and bison. Characteristic
      signals acting as markers are observed for each species. Moreover, the data are
      evaluated by principle component analysis (PCA) and support vector machines
      (SVM). A 100% correct species recognition between human and nonhuman species is
      achieved using radial basis kernel function (RBF) and standardized data. The
      research study shows that 1H NMR spectroscopy is a powerful tool for
      differentiating human and nonhuman blood showing a great significance to forensic
      science.

PMID- 27885431
TI  - Forensic age assessment of asylum seekers in Finland.
AB  - In Finland, forensic age assessment is strictly regulated by legislation.
      According to the Aliens Act (301/2004) and the amendment of the Act (549/2010),
      the police authorities, the frontier guard authorities, and the immigration
      authorities have the right to refer asylum seekers to the University of Helsinki,
      Department of Forensic Medicine, for age assessment. These assessments are
      especially performed to solve if the person is of major age, the cutoff being 18
      completed years. The forensic age assessment is largely based on dental
      development, since the special permit of the Radiation and Nuclear Safety
      Authority (STUK) to the Department of Forensic Medicine of the University of
      Helsinki, allowing the use of ionizing radiation for non-medical purposes,
      includes dental and hand X-rays. Forensic age assessment is always performed by
      two forensic odontologists. In 2015, the total number of forensic age assessment
      examinations was 149, and the countries of origin of the asylum seekers were most
      commonly Iraq, Afghanistan, and Somalia. The current legislation on forensic age
      assessment has been well received and approved. Radiological and other
      examinations can be performed in different parts of Finland, but the forensic
      odontologist at the University of Helsinki is always involved in the process and
      ensures joint quality standards for the forensic age assessment.

PMID- 27885432
TI  - Immunohistochemical detection of early myocardial infarction: a systematic
      review.
AB  - The postmortem diagnosis of early myocardial infarction is a challenge for
      forensic pathologists because the routine histology is neither specific. Many
      authors have suggested the use of the immunohistochemistry to fill the gaps in
      the histological diagnosis of early myocardial infarction. This review aims to
      analyse advances of immunohistochemical detection of early cardiac damage due to
      ischaemia. To this purpose, we reviewed experimental studies that investigated
      immunohistochemical markers and their estimated timing of expression. The review
      was performed according to specific inclusion and exclusion criteria, and a total
      of 23 studies assessing the immunohistochemical markers for the diagnosis and
      timing of early myocardial infarction were identified. The literature review
      highlights that the analysed markers are complement components, others being
      inflammatory mediators, cardiac cell proteins, plasma proteins, stress or hypoxia
      induced factors and proteins associated with heart failure. All studies
      demonstrate the effectiveness of the tested markers in the early detection of
      myocardial infarction in both animal and human samples.

PMID- 27885433
TI  - Discussing sexuality with patients with Parkinson's disease: a survey among Dutch
      neurologists.
AB  - Sexual functioning is often impaired in patients with Parkinson's disease (PD)
      and may affect quality of life of patients and their spouse. However, little is
      known about the practice patterns of neurologists with regard to discussing
      sexuality in this field. The aim of this cross-sectional study was to evaluate to
      what extent neurologists discuss sexuality with PD patients. A 22-item
      questionnaire was sent to 139 neurologists specializing in PD. The survey
      contained questions about their attitudes, knowledge, and practice patterns with
      respect to sexual dysfunction (SD) in patients with PD. The response rate of the
      survey was 66.9%. Most participants (56.8%) stated that they address sexuality in
      less than half of their PD patients. High age of patients (42.0%), insufficient
      consultation time (37.5%), and a lack of patients' initiative to raise the topic
      themselves (36.4%) were frequently reported barriers towards discussing
      sexuality. The majority of participants considered that discussing sexuality is a
      responsibility that lay with neurologists (85.2%), nurses (73.9%), and patients
      (72.7%). One quarter of the neurologists reported to have insufficient or no
      knowledge on SD. The majority of participants regarded screening for SD important
      or slightly important (85.2%). A large proportion of Dutch neurologists
      specializing in PD do not routinely discuss sexuality with their PD patients.
      Sexual healthcare in PD patients may benefit from time-efficient tools and
      agreements on who is responsible for discussing SD. Furthermore, recommendations
      in PD guidelines on screening and managing SD should be adapted to fit everyday
      practice.

PMID- 27885434
TI  - Evaluation of miR-21 and miR-375 as prognostic biomarkers in oesophageal cancer
      in high-risk areas in China.
AB  - MicroRNAs have been associated with prognosis in oesophageal cancer (EC),
      suggesting that miRNAs could play a role in guiding treatment decisions. The aim
      of this study was to evaluate the prognostic potential of miRNAs found to be
      associated with zinc deficiency in a geographical area with a high incidence of
      EC. miRNAs found to be associated with zinc deficiency were isolated from EC cell
      lines cultured with various Zn levels. The expression levels of the miRNAs were
      quantified using qRT-PCR. The potential prognostic value of the selected miRNAs
      was assessed in a cohort study of 88 patients from an area in China with a high
      incidence of EC. Correlations between miRNAs and patient characteristics were
      assessed using chi2 statistical tests or Fisher's exact test. A Cox proportional
      hazards model was used to assess the correlations between miRNAs and overall
      survival (OS). Forest plots were performed to evaluate the prognostic impact of
      the miRNAs examined in the present study in the Asian population. The expression
      levels of miR-21, miR-31, miR-93 and miR-375 were different when Zn levels were
      varied in EC cell lines, but only miR-21 and miR-375 were associated with patient
      characteristics and prognosis in patients with EC from an area of China with a
      high incidence of EC. The patients expressing high levels of miR-21 had poor OS
      (HR 2.15, 95% CI 1.16-3.97), whereas those with high levels of miR-375 had
      improved OS (HR 0.47, 95% CI 0.26-0.87).The patients with both a high level of
      miR-375 and a low level of miR-21 had significantly better outcomes. Forest plots
      based on an analysis of this Asian population indicated that a high level of miR
      21 significantly predicted a shortened OS (HR 1.83, 95% CI 1.42-2.37), whereas a
      high level of miR-375 was significantly correlated with increased survival (HR
      0.56, 95% CI 0.43-0.73). MiR-21 and miR-375 could be used as prognostic
      biomarkers in areas with a high incidence of EC, and combining these markers may
      results in a better effect.

PMID- 27885436
TI  - Effects of aluminum trichloride on the cartilage stimulatory growth factors in
      rats.
AB  - Aluminum (Al) is considered to be a potentially toxic metal and inhibits
      cartilage formation. Transforming growth factor beta1 (TGF-beta1) and bone
      morphogenetic protein 2 (BMP-2) are cartilage stimulatory growth factors, which
      play important roles in regulating the cartilage formation. To investigate the
      effects of aluminum trichloride (AlCl3) on the regulation of cartilage formation.
      Eighty Wistar rats were orally exposed to 0 (control group), 0.4 g/L (low-dose
      group), 0.8 g/L (mid-dose group) and 1.6 g/L (high-dose group) AlCl3 for 120
      days, respectively. The rats body weight were decreased, the cartilage
      histological structure were disrupted, the cartilage and serum contents of Al and
      the serum level of C-telopeptide of type II collagen were all increased, the
      serum level of type II collagen (Col II) and alkaline phosphatase (ALP), and the
      mRNA expressions of TGF-beta1, BMP-2, ALP and Col II were all decreased in the
      AlCl3-treated groups compared with those in control group. These results indicate
      that AlCl3 inhibits the cartilage formation through inhibition of the cartilage
      stimulatory growth factors expressions.

PMID- 27885437
TI  - Association of STAT5A Gene Variants with Milk Production Traits in Agerolese
      Cattle.
AB  - Two polymorphisms at STAT5A gene were investigated in a sample of Agerolese cows.
      The aims of the present study were to estimate the allele and genotype
      frequencies and to investigate the relationship among genotypes and milk
      production traits. Milk production traits were analyzed for each animal in the
      first, second, third, and fourth lactation. No genetic variability was found at
      STAT5A/AvaI locus. At STAT5A/MslI locus, the frequencies of T and C alleles were
      0.875 and 0.125, respectively. Significant differences between genotypes were
      found: TT cow produced a milk with a higher content of fat and protein when
      compared with TC.

PMID- 27885435
TI  - Comparison of immunophenotypes of primary breast carcinomas and multiple
      corresponding distant metastases: an autopsy study of 25 patients.
AB  - Phenotypical change in metastatic breast carcinoma has widely been accepted as an
      inherent biological feature rather than technical fault. We analyzed the
      immunohistochemical phenotype and histopathological features of 25 primary breast
      carcinomas and 90 corresponding distant metastases in 23 organs retrospectively.
      Histological slides were reviewed for prognostic and predictive factors. Overall,
      metastases were more similar to each other and often differed from the primary
      tumor. We created a 3-step grouping system based on the localization of
      metastases. Regions: tumors metastasizing to the abdominal region were likely to
      lose ER (p = 0.002); we detected loss of PR in metastases to the thorax (p =
      0.039) and abdomen (p < 0.001). Organ systems: loss of ER and PR was observed in
      metastases to the gastrointestinal system (p = 0.026 and p = 0.001,
      respectively), in the respiratory system only the loss of PR was significant (p =
      0.05). Individual organs: the primaries were likely to lose the hormone receptors
      in liver metastases (ER p = 0.026; PR p = 0.004). In lung metastases only loss of
      PR was apparent (p = 0.049). We did not observe significant change in HER2
      status, regarding Ki67 change occurred only in bone metastases compared to the
      primary (p = 0.048). 7/25 patients' distant metastases had heterogeneous
      immunoprofiles. The later the metastasis was discovered the more likely it had a
      differing IHC profile compared to the primary tumor, patients who had longer OS
      had a higher chance to develop a discordant metastasis. Immunoprofile of
      metastases may differ from primary breast cancer and from each other, probably
      resulting in different response to therapy.

PMID- 27885440
TI  - ?

PMID- 27885439
TI  - Weekly paclitaxel plus carboplatin with or without trastuzumab as neoadjuvant
      chemotherapy for HER2-positive breast cancer: loss of HER2 amplification and its
      impact on response and prognosis.
AB  - PURPOSE: Neoadjuvant chemotherapy (NCT) plus anti-HER2 agents are the standard of
      care for locally advanced HER2-positive breast cancer. The aim of this study was
      to evaluate the prevalence and prognostic impact of HER2 loss in patients with
      HER2-positive disease treated with neoadjuvant therapy with or without
      trastuzumab. METHODS: 549 consecutive HER2-positive patients were included in
      this study. 379 patients were treated with paclitaxel, carboplatin, and
      trastuzumab (PCH cohort) and 170 were treated with paclitaxel and carboplatin
      only (PC cohort). Conversion of biomarkers before and after NCT was evaluated via
      immunohistochemistry (IHC) test. Cox regression model was used to investigate
      prognostic markers to relapse-free survival (RFS). RESULTS: 50.9% patients were
      considered as pCR responder in PCH cohort, whereas only 25.9% of patients
      experienced pCR in PC cohort (P < 0.001). HER2 loss were more frequently shown in
      PCH cohort with a proportion of 19.8%, compared to 9.4% in PC cohort (P = 0.009).
      In PCH cohort, patients with a loss of HER2 expression tended to have a higher
      risk of relapse compared to patients with maintained HER2 expression (HR = 2.639,
      95% CI 1.103-6.311, P = 0.029). However, it did not correlate to patient outcome
      in the PC cohort (P = 0.296). Loss of HER2 was also correlated to ER conversion
      in PCH cohort. CONCLUSION: Our study has provided new evidence that anti-HER2
      treatment has a significant impact on HER2 loss. Far more importantly, the loss
      of HER2 amplification could identify non-pCR patients with high risk of disease
      relapse, which might help in tailoring following systemic treatment.

PMID- 27885441
TI  - Bayesian comparative assessment of diagnostic accuracy of low-dose CT scan and
      ultrasonography in the diagnosis of urolithiasis after the application of the
      STONE score.
AB  - OBJECTIVE: The objective of our study was to assess the diagnostic quality of low
      dose computed tomography (CT) when compared to ultrasound (US) in diagnosis of
      urolithiasis using STONE score as a predictor of pre-test probability and the
      Bayesian statistical model to calculate post-test probabilities (POST) for both
      diagnostic tests. METHODS: STONE score was used to form risk groups to obtain pre
      test probabilities. Likelihood ratios (LR) were calculated from external data for
      low-dose CT and US. POST were obtained using pre-test probabilities and
      likelihood ratios with Bayesian nomogram. Absolute (ADG) and relative (RDG) gains
      in diagnostic value were calculated. RESULTS: Calculated +LR for US was 12 and 
      LR was 0.32; for CT, +LR was 19 and -LR 0.04. +LR and low STONE for US yielded
      POST 57% and RDG 470%; intermediate STONE POST 92% and RDG 84%; and high STONE
      POST 99% and RDG 10%. -LR and low STONE for US POST 3% and RDG -70%; intermediate
      POST 24% and RDG -52%; and high STONE POST 74% and RDG -17.7%. +LR and low STONE
      for CT POST 68% and RDG 580%; moderate STONE POST 95% and RDG 90%; and high STONE
      POST 99% and RDG 10%. -LR and low STONE for CT POST 0% and RDG -100%;
      intermediate POST 4% and RDG -92%; and high STONE POST 26% and RDG -71.1%. ANOVA
      calculations comparing CT vs US for +LR showed no statistical significance (P
      value = 0.9893; LR- P value = 0.5488). CONCLUSION: Bayesian statistical analysis
      demonstrated slight superiority of CT scan over US on STONE score low- and
      moderate-risk stratified subtypes, whereas no significant advantage was seen when
      evaluating high-probability patients.

PMID- 27885438
TI  - Phylogeny-guided (meta)genome mining approach for the targeted discovery of new
      microbial natural products.
AB  - Genomics-based methods are now commonplace in natural products research. A
      phylogeny-guided mining approach provides a means to quickly screen a large
      number of microbial genomes or metagenomes in search of new biosynthetic gene
      clusters of interest. In this approach, biosynthetic genes serve as molecular
      markers, and phylogenetic trees built with known and unknown marker gene
      sequences are used to quickly prioritize biosynthetic gene clusters for their
      metabolites characterization. An increase in the use of this approach has been
      observed for the last couple of years along with the emergence of low cost
      sequencing technologies. The aim of this review is to discuss the basic concept
      of a phylogeny-guided mining approach, and also to provide examples in which this
      approach was successfully applied to discover new natural products from microbial
      genomes and metagenomes. I believe that the phylogeny-guided mining approach will
      continue to play an important role in genomics-based natural products research.

PMID- 27885443
TI  - Roles of the haustorium and endosperm during the development of seedlings of
      Acrocomia aculeata (Arecaceae): dynamics of reserve mobilization and
      accumulation.
AB  - The mobilization of palm seed reserves is a complex process because of the
      abundance and diversity of stored compounds and results from the development of a
      highly specialized haustorium. This work focused on the important Neotropical
      oleaginous palm Acrocomia aculeata, with the aim of defining phases of seedling
      development associated with mobilization of reserves and elucidating the role of
      haustorium and endosperm in this process. Standard methods were performed,
      including biometric, anatomical, and histochemical analyses, as well as the
      evaluation of the activities of the enzymes endo-beta-mannanase and lipase,
      throughout the reserve mobilization in seeds during germination and in seedlings.
      Seeds of A. aculeata stored large quantities of proteins, lipids, and
      polysaccharides in the embryo and endosperm. The mobilization of reserves
      initiated in the haustorium during germination and subsequently occurred in the
      endosperm adjacent to the haustorium, forming a gradually increasing zone of
      digestion. Proteins and polysaccharides were the first to be mobilized, followed
      by lipids and cell wall constituents. The haustorium activates and controls the
      mobilization, forming transitory reserves and translocating them to the
      vegetative axis, while the endosperm, which also has an active role, serves as a
      site of intense enzymatic activity associated with protein bodies. Seedling
      development can be described as occurring in six phases over a long period
      (approximately 150 days) due to the large amount of seed reserves. This process
      exhibits an alternation between stages of accumulation and translocation of
      protein, lipid, and carbohydrate reserves in the haustorium, which favors the
      seedling establishment and the reproductive success of the species.

PMID- 27885444
TI  - Emergency Pacing via the Umbilical Vein and Subsequent Permanent Pacemaker
      Implantation in a Neonate.
AB  - A dying neonate with congenital complete atrioventricular block underwent an
      emergency temporary pacing via the umbilical vein 1 h after birth. Implantation
      of a permanent epicardial pacemaker system was performed at the age of 10 days.
      During the follow-up period of 3 months, the child had been growing well with the
      VVIR pacemaker.

PMID- 27885442
TI  - Patterns and trends of pediatric bloodstream infections: a 7-year surveillance
      study.
AB  - We characterize the epidemiology of pediatric bloodstream infections (BSIs) in
      Switzerland. We analyzed pathogen distribution and resistance patterns in
      monomicrobial and polymicrobial BSIs in children from 2008 to 2014 using data
      from the Swiss antibiotic resistance centre (ANRESIS). A confirmatory statistical
      analysis was performed comparing pathogens and resistance across 20 acute care
      hospitals. We identified 3,067 bacteremia episodes, of which 1,823 (59 %) were
      considered true BSI episodes. Overall, S. aureus (16.5 %, 300) was the most
      frequent pathogen, followed by E. coli (15.1 %, 276), coagulase-negative
      staphylococci (CoNS, 12.9 %, 235), S. pneumoniae (11.1 %, 202) and non-E. coli
      Enterobacteriaceae (8.7 %, 159). S. aureus and E. coli showed similar frequencies
      in all of the variables analyzed (e.g., hospital acquisition, hospital type,
      medical specialty). The proportion of these microorganisms did not change over
      time, resistance rates remained low (4.3 % methicillin resistance in S. aureus;
      7.3 % third-/fourth-generation cephalosporin resistance in E. coli), and no
      significant resistance trends were observed. We observed a 50 % increase of CoNS
      BSIs from 2008 (9.8 %, 27) to 2014 (15.2 %, 46, p value for trend = 0.03). S.
      pneumoniae decreased from 17.5 % (48) to 6.6 % (20) during that timeframe (p for
      trend = 0.007). S. aureus and E. coli remained the most significant pathogens
      among pediatric BSIs in Switzerland, exhibiting low resistance rates. CoNS
      accounted for a greater proportion of BSIs over time. The decrease in bacteremic
      pneumococcal infections can likely be attributed to the introduction of the 13
      valent conjugate vaccine in 2011.

PMID- 27885445
TI  - Limited Ventricular Preload is the Main Reason for Reduced Stress Reserve After
      Atrial Baffle Repair.
AB  - The atrial baffle repair (ABR) significantly improved the fate of patients with
      transposition of the great arteries (TGA). However, these patients show impaired
      exercise tolerance and some present severe decline of systemic ventricular
      function. Intrinsic myocardial weakness, low heart rate response to exercise and
      diastolic filling impairment are discussed to be causative. Forty-nine long-term
      survivors with TGA (median age 23.7 year) after ABR were catheterized with
      measured oxygen consumption in four conditions (baseline, volume, atrial pacing,
      dobutamine) and the results were compared to 10 normal controls. Median cardiac
      output was significantly lower in the ABR group (2.2 vs. 2.6 l/min/m2; p =
      0.015), and systemic resistance was significantly elevated (28.9 vs. 22.2 U m2; p
      = 0.04) in comparison with normals. While stroke volume rose by 27% in the
      control group, it dropped by 7% in patients after ABR at atrial pacing (80/min).
      Stroke volume increase after dobutamine was significantly lower after ABR in
      comparison with normal controls (34 vs. 106%; p = 0.001). Higher NYHA class (p =
      0.043), degree of tricuspid regurgitation (p = 0.009) and ventricular function (p
      = 0.028) were associated with lower stroke volume increase. Limited exercise
      capability of patients after ABR for TGA is primarily due to limited diastolic
      filling of the ventricles due to stiff non-compliant atrial pathways. Elevated
      systemic resistance may lead to severe myocardial hypertrophy with possible
      ischemia and contribute to the multifactorial decline of ventricular function in
      some patients.

PMID- 27885446
TI  - Post-cardiotomy Rescue Extracorporeal Cardiopulmonary Resuscitation in Neonates
      with Single Ventricle After Intractable Cardiac Arrest: Attrition After Hospital
      Discharge and Predictors of Outcome.
AB  - Extracorporeal cardiopulmonary resuscitation (ECPR) in children with cardiac
      arrest refractory to conventional cardiopulmonary resuscitation (CPR) has been
      reported with encouraging results. We reviewed outcomes of neonates with
      functional single ventricle (FSV) surviving post-cardiotomy ECPR after hospital
      discharge. Fifty-eight patients who required post-cardiotomy extracorporeal
      membrane oxygenation (ECMO) since the introduction of our ECPR protocol (January
      2007-December 2011) were identified. Forty-one were neonates. Survival analysis
      was conducted. Of 41 neonates receiving post-cardiotomy ECMO, 32 had FSV. Twenty
      one had ECPR. Fourteen underwent Norwood operation (NO) for hypoplastic left
      heart syndrome (HLHS). Seven had non-HLHS FSV. Four (of 7) underwent modified
      NO/DKS with systemic-to-pulmonary shunt (SPS), 2 SPS only and 1 SPS with
      anomalous pulmonary venous connection repair. Mean age was 6.8 +/- 2.1 days. ECMO
      median duration was 7 days [interquartile range (IQR25-75: 4-18)]. Survival to
      ECMO discontinuation was 72% (15 of 21 patients) and at hospital discharge 62%
      (13 of 21 patients). The most common cause of late attrition was cardiac. At last
      follow-up (median: 22 months; IQR25-75: 3-36), 47% of patients were alive.
      Duration of ECMO and failure of lactate clearance within 24 h from ECMO
      deployment determined late survival after hospital discharge (p < 0.05). Rescue
      post-cardiotomy ECMO support in neonates with FSV carries significant late
      attrition. ECMO duration and failure in lactate clearance after deployment are
      associated with unfavorable outcome. Emphasis on CPR quality, refinement of
      management directives early during ECMO and aggressive early identification of
      patients requiring heart transplantation might improve late survival.

PMID- 27885447
TI  - Contrast extravasation through MRI precedes cerebral hemorrhage in a patient with
      eclampsia.

PMID- 27885449
TI  - ?

PMID- 27885448
TI  - Cognitive dysfunction in patients with multiple sclerosis treated with first-line
      disease-modifying therapy: a multi-center, controlled study using the BICAMS
      battery.
AB  - Multiple sclerosis (MS) can impair cognitive functions even in the early stages.
      The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
      battery is very short and highly sensitive and can be used to evaluate cognitive
      status in the disease. Several clinical trials have shown beneficial effects of
      disease-modifying drugs (DMDs) on long-term cognitive measures which may even
      reduce cognitive deficits in MS patients. Relapsing remitting MS patients using
      DMDs were enrolled in the study and monitored for 12 months. BICAMS and the
      Expanded Disability Status Scale were applied to the study group. We evaluated
      and monitored 161 newly diagnosed cases of definite MS by the end of the trial.
      110 patients (68.2%) were female. One hundred and two healthy subjects (female to
      male ratio 68:34) were enrolled into the study. MS patients were categorized into
      three DMT groups: IFNB1-a SC, IFNB1-b, and GA. Mean scores of all three cognitive
      tests (SDMT, BVMT-R, and CVLT-II) were significantly higher in the control group
      than in the MS patients. The number of cognitively impaired patients decreased
      from 31.7 to 21.7% on the basis of CVLT (p = 0.024), and 42 (26.1%) to 30 (18.6%)
      on the basis of BVMT-R at month 12. A significant difference was determined in
      terms of cognitive status between MS patients using both IFNB and GA and the
      healthy control group. Ours is the first study to compare IFNB and GA in terms of
      evaluating cognitive involvement and to use the BICAMS battery in monitoring
      treatment.

PMID- 27885450
TI  - ?

PMID- 27885451
TI  - Increased nucleophosmin expression is a strong predictor of recurrence and
      prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing
      radical nephroureterectomy.
AB  - PURPOSE: We aimed to evaluate whether increased nucleophosmin expression predicts
      recurrence and survival in upper tract urothelial carcinoma (UTUC). METHODS:
      Specimens from 101 patients with N0M0 UTUC undergoing radical nephroureterectomy
      were evaluated. Nucleophosmin expression was determined immunohistochemically and
      categorized into two groups according to nucleophosmin staining intensity. The
      association between nucleophosmin expression and various clinicopathological
      factors including Ki-67 expression was analyzed. Multivariate analyses were
      performed to identify the independent predictors of extraurothelial recurrence
      and cancer-specific survival. RESULTS: High nucleophosmin expression was
      significantly correlated with tumor location, pT >=3, lymphovascular invasion,
      lymph node metastasis, and high Ki-67 expression. Patients whose tumors
      demonstrated high nucleophosmin expression had a significantly higher rate of
      extraurothelial recurrence and a lower survival rate than those with low
      nucleophosmin expression. Multivariate analysis showed that pT >=3, lymph node
      metastasis, high nucleophosmin expression, and high Ki-67 expression were
      independent predictors of extraurothelial recurrence. When patients were
      stratified into three groups according to the number of risk factors, the 2-year
      extraurothelial recurrence-free survival rates were 92.9% in patients with 0 or 1
      risk factor, 76.5% in patients with 2 risk factors, and 9.1% in patients with 3
      or 4 risk factors. Regarding cancer-specific survival, lymphovascular invasion
      and high nucleophosmin expression were independent predictors. CONCLUSIONS:
      Increased nucleophosmin expression was a strong predictor of extraurothelial
      recurrence and cancer-specific survival in patients with N0M0 UTUC undergoing
      radical nephroureterectomy. Our risk stratification models integrating
      nucleophosmin expression may provide valuable information on disease recurrence
      and prognosis.

PMID- 27885453
TI  - [Innovative radionuclide use in urology].

PMID- 27885454
TI  - [The urologist Eugen Joseph and his suicide].

PMID- 27885452
TI  - The zero ischemia index (ZII): a novel criterion for predicting complexity and
      outcomes of off-clamp partial nephrectomy.
AB  - PURPOSES: Although several anatomical classification systems that aimed to
      standardize the description of renal tumors were previously reported, a special
      classification system is required to help predict the complexity and
      perioperative outcomes of off-clamp nephron-sparing surgery (NSS). We developed a
      novel criterion-zero ischemia index (ZII), aiming to help predict the
      perioperative outcomes after off-clamp NSS and guide patient selection. METHODS:
      We retrospectively evaluated 149 patients between June 2009 and July 2014 in our
      institution who underwent off-clamp NSS with available computed tomography
      images. ZII was defined as the product of the tumor diameter and depth within
      renal parenchyma. ZII was then analyzed to investigate its association with
      perioperative outcomes. A specific ZII score was further selected to best guide
      patient selection in off-clamp NSS. RESULTS: ZII was significantly associated
      with estimated blood loss >500 mL (OR 1.270, 95% CI 1.036-1.557, p = 0.021),
      operative time >2 h (OR 1.286, 95% CI 1.051-1.573, p = 0.014), surgical
      complications (OR 1.251, 95% CI 1.035-1.511, p = 0.020), overall complications
      (OR 1.208, 95% CI 1.016-1.436, p = 0.032), and >10% decrease in estimated
      glomerular filtration rate (OR 1.362, 95% CI 1.045-1.776, p = 0.022). Patients
      with ZII > 6 may bear a higher risk of hemorrhage, perioperative complications,
      and a longer operative time, if they underwent an off-clamp NSS, compared to
      those with ZII <= 6. CONCLUSIONS: The ZII is a novel and readily measurable
      criterion which can help predict renal complexity of tumor and risk of
      perioperative outcomes after off-clamp NSS. ZII = 6 is established as a
      preliminary threshold for patient selection of off-clamp NSS. A more robust
      criterion is to be validated with more samples in a prospective study.

PMID- 27885455
TI  - [PSMA-radioguided surgery in localized recurrent prostate cancer : Current and
      future aspects].
AB  - Recently, PSMA-radioguided surgery (PSMA-RGS) was introduced for targeted
      resection of localized prostate cancer recurrence. Prerequisite for preoperative
      patient selection and localization of tumor recurrence is a positive 68Ga-HBED-CC
      PSMA positron emission tomography (PET) scan with preferably only singular soft
      tissue or lymph node recurrence. After injection of In-PSMA I&T or Tc-PSMA-I&S
      single photon emission computer tomography (SPECT)/computer tomography (CT)
      examination is performed in every patient to verify radiotracer uptake in tumor
      lesions. In a preliminary study, 111In-PSMA I&T SPECT/CT could detect about half
      of the 68Ga-HBED-CC PSMA PET-positive lesions, while nearly all PET-positive
      lesions could be detected using PSMA-RGS and also five additional lesions
      compared to 68Ga-HBED-CC-PSMA PET. Follow-up data from 55 patients show a PSA
      reduction >50% and >90% in 44 (80%) and 29 (53%) patients, respectively. In 34
      (62%) patients, a PSA drop to <0.2 ng/ml was observed. In all, 15 (27%) patients
      received further PC-specific treatment; the remaining 40 (73%) patients did not
      undergo further treatment. In 33% of patients, surgery-related complications were
      noted; however, most were regarded as minor. Thus, PSMA-RGS seems to be of high
      value in patients with localized prostate cancer recurrence with exact
      localization and resection of metastatic tissue. However, patient selection based
      on 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain
      satisfactory oncological results.

PMID- 27885456
TI  - [Intravesical radioimmunotherapy of carcinoma in situ of the urinary bladder
      after BCG failure].
AB  - BACKGROUND: In failure to respond to bacillus Calmette-Guerin (BCG) in patients
      with carcinoma in situ (CIS) of the urinary bladder, radical cystectomy remains
      the mainstay after BCG failure. OBJECTIVES: The aim of this pilot study was to
      evaluate tolerability and safety of the alpha-emitter radioimmunoconjugate
      instillation in patients after BCG failure. MATERIALS AND METHODS: Nine patients
      were included. After emptying the bladder via a transurethral catheter, Bi-213
      anti-EGFR-mAb was instilled. Treatment was terminated by emptying of the
      radioimmunoconjugate from the bladder 120 min after instillation. Efficacy was
      evaluated via endoscopy and histology 6 weeks after instillation. RESULTS: All
      patients showed excellent toleration of the treatment without any side effects.
      Treatment resulted in complete eradication of tumor cells in 3 patients and
      persistent tumor detection in the other 6 patients. CONCLUSIONS: Intravesical
      instillation of Bi-213-anti-EGFR-mAb is a promising therapeutic option for
      treatment of in situ bladder cancer after BCG failure for patients who wish to
      preserve the bladder.

PMID- 27885458
TI  - [Enuresis and pediatric urinary incontinence : Diagnostics and therapy].
AB  - Differentiated non-invasive diagnostic procedures allow a discrimination between
      nocturnal enuresis and behavior-linked urinary incontinence in children with
      daytime symptoms, which are different entities of a pathological pediatric
      micturition syndrome. The article describes the diagnostic procedure as well as
      the therapeutic approach to all forms of micturition disorders in childhood. All
      behavioral, medical and biofeedback therapeutic methods according to the recently
      published S2k guidelines from the Association of the Scientific Medical Societies
      in Germany (AWMF) on enuresis and non-organic (functional) incontinence in
      children and adolescents are mentioned and discussed.

PMID- 27885457
TI  - [PSMA-targeted radioligand therapy in prostate cancer].
AB  - Radioligand therapy (RLT) directed against prostate-specific membrane antigen
      (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing
      prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have
      been developed that can be labeled with beta-radiating lutetium-177. These are
      currently applied in compassionate use programs to treat metastatic castration
      resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered
      in several nuclear medicine departments throughout Germany. Several retrospective
      case series demonstrate its activity with a prostate-specific antigen (PSA)
      decrease >50% in 30-60% of mCRPC patients. The toxicity seems to be low.
      Hematologic grade 4 toxicity has not been observed and grade 3 toxicities rarely
      occur. The main nonhematologic adverse events are intermittent dry mouth because
      of unspecific PSMA expression in the salivary glands as well as fatigue and
      nausea. Currently there are no prospective studies available for evaluation of
      PSMA-targeted RLT and a survival benefit over approved standard therapies such as
      abiraterone, enzalutamide, radium-223-dichloride, docetaxel or cabazitaxel has
      not been shown. PSMA-targeted RLT should therefore currently only be offered
      after critical evaluation in patients who exhausted the approved standard
      therapies.

PMID- 27885459
TI  - Diabetes prevalence in patients with takotsubo syndrome in a Polish cohort: the
      meaning of 'controls'.

PMID- 27885461
TI  - Prevention and treatment effect of evogliptin on hepatic steatosis in high-fat
      fed animal models.
AB  - Dipeptidyl peptidase 4 (DPP4) is an adipokine that interrupts insulin signaling.
      The resulting insulin resistance exacerbates hepatic steatosis. We previously
      reported that the novel DPP4 inhibitor evogliptin improves insulin resistance.
      This study aimed to verify the therapeutic potential of evogliptin for fatty
      liver. Evogliptin treatment was initiated simultaneously with a high-fat diet
      (HFD) feeding in normal mice and in a post-24 week HFD-fed rats. In a prevention
      study, insulin sensitivity was preserved in evogliptin-treated mice after a 16
      week treatment. Overall plasma lipid levels stayed lower and hepatic lipid
      accumulation was drastically suppressed by evogliptin treatment. Evogliptin
      reduced hepatic expression of Srebf1, a key transcriptional factor for
      lipogenesis. Additionally, DPP4 inhibitor-treated mice showed less weight gain.
      In a treatment study, after evogliptin treatment for 14 weeks in pre-established
      HFD-fed obese rats, weight loss was marginal, while hepatic lipid accumulation
      and liver damage assessed by measuring plasma aminotransferase levels were
      completely resolved, suggesting weight loss-independent beneficial effects on
      fatty liver. Moreover, reduction in plasma non-esterified fatty acids supported
      the improvement of insulin resistance by evogliptin treatment. Conclusively, our
      findings suggest that evogliptin treatment ameliorates fatty liver by increasing
      insulin sensitivity and suppressing lipogenesis.

PMID- 27885462
TI  - The cytoprotective effect of Rumex Aquaticus Herba extract against hydrogen
      peroxide-induced oxidative stress in AGS cells.
AB  - The Rumex Aquaticus Herba extract containing quercetin-3-beta-D
      glucuronopyranoside (ECQ) has been reported to exhibit various pharmacological
      activities, including anti-inflammatory and anti-oxidative effects. This plant
      has been traditionally used for the treatment of diarrhea, disinfestation, edema
      and jaundice, and as an antipyretic drug. The aim of the present study was to
      investigate the ability of ECQ to protect against oxidative damage and to
      determine its signaling mechanism in AGS cells. The protein expressions of heme
      oxygenase-1 (HO-1) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were
      measured by Western blots. Cell viability was measured by MTT assay.
      Intracellular reactive oxygen species (ROS) levels were measured using 2',7'
      dichlorofluorescein diacetate. Glutathione peroxidase levels were measured using
      kits. The protein expressions of HO-1 and its upstream mediator, Nrf2, increased
      after ECQ treatment. The HO-1 inhibitor, ZnPP, repressed the protective effect of
      ECQ on H2O2-induced cell damage. We found that LY294002, a specific PI3 K/Akt
      inhibitor, suppressed ECQ-induced HO-1 expression. ECQ significantly attenuated
      H2O2-induced cytotoxicity and ROS generation. Also, ECQ enhanced the antioxidant
      enzyme activities of glutathione peroxidase. These results suggest that ECQ
      exerts a cytoprotective effect against H2O2-induced oxidative stress by
      upregulation of Nrf2/HO-1 via the PI3 K/Akt pathway.

PMID- 27885463
TI  - Molecular and morphological descriptions of Ceratomyxa collarae n. sp. and
      Ceratomyxa leucosternoni n. sp. from marine ornamental fishes of Indian waters.
AB  - Two novel species of Ceratomyxa infecting marine ornamental fishes from Indian
      waters are described. Marine ornamentals, Chaetodon collare and Chaetodon
      decussatus, collected from Vizhinjam, along the southwest coast of India and
      Acanthurus leucosternon collected from Lakshadweep islands of Arabian Sea
      revealed Ceratomyxa infections in their gall bladders. Mature spores of
      Ceratomyxa from Chaetodon collare and Chaetodon decussatus were elongate and
      slightly crescentic, with rounded ends, and measured 5.20 +/- 0.32 MUm in length
      and 16.32 +/- 1.29 MUm in thickness. Polar capsules spherical, equal in size and
      measured 2.23 +/- 0.16 MUm long and 2.24 +/- 0.20 MUm wide. Posterior angle
      measured 157.75 +/- 8.650. Principle Component Analysis and molecular analysis
      using partial SSUrDNA sequences showed the isolates from these two hosts to be
      identical. Morphological, morphometric and molecular analysis using partial
      SSUrDNA sequences revealed the taxonomic novelty of isolates and are hence
      treated as Ceratomyxa collarae n. sp. Mature spores of Ceratomyxa from Acanthurus
      leucosternon were elongate, slightly tapering with rounded ends, and measured
      7.34 +/- 0.92 MUm in length and 24.37 +/- 2.34 MUm in thickness. Shell valves
      were equal, joined by a narrow suture line. Polar capsules spherical in shape,
      equal in size, 2.59 +/- 0.32 MUm long and 2.46 +/- 0.32 MUm wide, and polar
      filament measured 18.68 +/- 2.54 MUm. Based on morphological, morphometric and
      molecular analyses, the present species of Ceratomyxa is distinct, considered as
      a new species and named Ceratomyxa leucosternoni n. sp. The paper also discusses
      the prevalence of the recovered parasites and host specificity of Ceratomyxa
      collarae n. sp.

PMID- 27885460
TI  - Contraceptive Considerations for Women with Gastrointestinal Disorders.
AB  - Gastroenterologists are in a unique position to assist women with chronic
      gastrointestinal disorders in order to optimize their health prior to pregnancy.
      Women, whether with chronic conditions or not, and their infants are more likely
      to be healthy when pregnancies are planned. Achieving a planned pregnancy at the
      ideal time or preventing pregnancy altogether requires the use of appropriate
      contraceptives. There is a broad range of contraceptives available to women in
      the USA, and the majority of women with digestive diseases will be candidates for
      all effective methods. Guidance from the Centers for Disease Control and
      Prevention aids clinicians in prescribing appropriate contraceptives to women
      with medical disorders. This review will focus on contraception for women with
      inflammatory bowel disease and chronic liver disease, including liver transplant.

PMID- 27885464
TI  - Erratum to: Evolutionary modularity and morphological integration in the haptoral
      anchor structures of Ligophorus spp. (Monogenea: Dactylogyridae).

PMID- 27885465
TI  - Multilocus sequence analysis of Giardia spp. isolated from patients with diarrhea
      in Austria.
AB  - Giardia duodenalis is a protozoan parasite causing intestinal infections in a
      wide range of mammals. Two distinct assemblages, A and B, infect humans
      predominantly; however, both are believed to be generally zoonotic. Giardia
      strains associated with infections in Austria have not been investigated at the
      molecular level. In this study, 65 human stool samples microscopically positive
      for Giardia spp. were subjected to DNA isolation and nested PCR targeting
      fragments of the glutamate dehydrogenase (gdh), triose phosphate isomerase (tpi),
      and beta-gardin (bg) genes. A total of 52 samples were successfully analyzed
      using PCR and DNA sequencing. Assemblage B was detected most frequently and
      accounted for 65.4% (34/52) of infections, while Assemblage A accounted for 34.6%
      (18/52). There was a high level of genetic diversity among the isolates with
      46.2% designated as sub-assemblage BIV (24/52), 25% sub-assemblage AII (13/52),
      19.2% sub-assemblage BIII (10/52), and 9.6% sub-assemblage AI (5/52). No mixed
      infections were detected. The results suggest that the majority of infections
      were imported and that endemic anthroponotic transmission plays a minor role in
      Austria.

PMID- 27885467
TI  - Response to letter to the Editors-Safety of long-term denosumab therapy.

PMID- 27885466
TI  - Molecular epidemiology and multilocus sequence analysis of potentially zoonotic
      Giardia spp. from humans and dogs in Jamaica.
AB  - Giardia spp. are the causative agents of intestinal infections in a wide variety
      of mammals including humans and companion animals. Dogs may be reservoirs of
      zoonotic Giardia spp.; however, the potential for transmission between dogs and
      humans in Jamaica has not been studied. Conventional PCR was used to screen 285
      human and 225 dog stool samples for Giardia targeting the SSU rDNA gene followed
      by multilocus sequencing of the triosephosphate isomerase (tpi), glutamate
      dehydrogenase (gdh), and beta-giardin (bg) genes. Prevalence of human infections
      based on PCR was 6.7 % (19/285) and canine infections 19.6 % (44/225). Nested PCR
      conducted on all 63 positive samples revealed the exclusive presence of
      assemblage A in both humans and dogs. Sub-assemblage A-II was responsible for
      79.0 % (15/19) and 70.5 % (31/44) of the infections in humans and dogs,
      respectively, while sub-assemblage A-I was identified at a rate of 15.8 % (3/19)
      and 29.5 % (13/44) in humans and dogs, respectively. The predominance of a single
      circulating assemblage among both humans and dogs in Jamaica suggests possible
      zoonotic transmission of Giardia infections.

PMID- 27885468
TI  - Staphylococcus lugdunensis infections, filling in the gaps: a 3-year
      retrospective review from a comprehensive cancer center.
AB  - OBJECTIVE: Staphylococcus lugdunensis is considered to be more aggressive than
      other coagulase-negative staphylococci (CoNS). There are gaps in knowledge
      regarding the importance of isolating S. lugdunensis from different sources and
      in different patient subsets. Our objective was to describe the spectrum,
      clinical manifestations, and outcomes of infections caused by S. lugdunensis in
      patients with cancer. METHODS: A retrospective review of all cancer patients from
      whom S. lugdunensis was isolated in a pure culture from clinically significant
      sites. RESULTS: Between 2011 and 2014, 2263 CoNS were isolated, of them 45 S.
      lugdunensis were isolated in a pure culture and were included in this analysis.
      Only three patients were neutropenic. Skin and skin structure infections (SSSIs)
      occurred most often (36 cases) followed by five blood stream infections, one of
      which had destructive endocarditis and four infections at other sites. Of the 36
      SSSIs, 29 were related to surgical or invasive procedures, and six of these
      involved an implanted medical device. All isolates were susceptible to
      vancomycin, 98% to levofloxacin and 89% to oxacillin. All patients responded to
      the therapy. CONCLUSIONS: Cancer patients including those with neutropenia do not
      appear to have an increased frequency of infections caused by S. lugdunensis.
      SSSIs are predominant and are often associated with surgical procedures and/or
      implanted medical devices. Blood stream infections caused by S. lugdunensis are
      uncommon but may have an increased rate of serious complications such as
      endocarditis. Nevertheless, these organisms are generally susceptible to multiple
      classes of antimicrobial agents, and the overall response to therapy is high.

PMID- 27885469
TI  - NEPA, a fixed oral combination of netupitant and palonosetron, improves control
      of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of
      chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral
      palonosetron.
AB  - PURPOSE: Antiemetic guidelines recommend co-administration of targeted
      prophylactic medications inhibiting molecular pathways involved in emesis. NEPA
      is a fixed oral combination of a new NK1 receptor antagonist (RA), netupitant
      (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5
      HT3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and
      vomiting (CINV) compared with oral PALO in a single chemotherapy cycle;
      maintenance of efficacy/safety over continuing cycles is the objective of this
      study. METHODS: This study is a multinational, double-blind study comparing a
      single oral dose of NEPA vs oral PALO in chemotherapy-naive patients receiving
      anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg
      (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25
      120 h) complete response (CR: no emesis, no rescue medication) in cycle 1.
      Sustained efficacy was evaluated during the multicycle extension by calculating
      the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by
      assessing the probability of sustained CR over multiple cycles. RESULTS: Of 1455
      patients randomized, 1286 (88 %) participated in the multiple-cycle extension for
      a total of 5969 cycles; 76 % completed >=4 cycles. The proportion of patients
      with an overall CR was significantly greater for NEPA than oral PALO for cycles 1
      4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %,
      respectively; p <= 0.001 each cycle). The cumulative percentage of patients with
      a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was
      well tolerated over cycles. CONCLUSIONS: NEPA, a convenient, guideline
      consistent, fixed antiemetic combination is effective and safe over multiple
      cycles of chemotherapy.

PMID- 27885470
TI  - A randomised controlled trial of transforaminal endoscopic discectomy vs
      microdiscectomy.
AB  - PURPOSE: Transforaminal endoscopic discectomy (TED) minimises paraspinal muscle
      damage. The aim of this trial was to compare clinical outcomes of TED to
      Microdiscectomy (Micro). METHODS: 143 patients, age 25-70 years and <115 kg, with
      single level lumbar prolapse and radiculopathy, were recruited and randomised. 70
      received TED under conscious sedation and 70 Micro under general anaesthesia.
      Oswestry Disability Index (ODI), visual analogue scores (VAS) of back and leg
      pain, and Short Form Health Survey indices (SF-36) were measured preoperatively
      and at 3, 12 and 24 months. RESULTS: All outcome measures improved significantly
      in both groups (p < 0.001). Affected side leg pain was lower in the TED group at
      2 years (1.9 +/- 2.6 vs 3.5 +/- 3.1, p = 0.002). Hospital stay was shorter
      following TED (0.7 +/- 0.7 vs 1.4 +/- 1.3 days, p < 0.001). Two Micro patients
      and five TED patients required revision giving a relative risk of revision for
      TED of 2.62 (95% CI 0.49-14.0). CONCLUSIONS: Functional improvements were
      maintained at 2 years in both groups with less ongoing sciatica after TED. A
      greater revision rate after TED was offset by a more rapid recovery.

PMID- 27885471
TI  - Modic changes in the adjacent vertebrae due to disc material infection with
      Propionibacterium acnes in patients with lumbar disc herniation.
AB  - INTRODUCTION: Modic changes (MCs) in vertebral bones are induced by two
      mechanisms of mechanical factors and infection. As Propionibacterium acnes (P.
      acnes) have been reported to be associated with LBP. The aim of this study is to
      evaluate the MCs in patients with disc herniation and positive for P. acnes.
      METHODS AND MATERIAL: A total of 120 patients with disc herniation surgery were
      enrolled into the study. The samples were excised during discectomy and then
      cultured in both anaerobic and aerobic incubations. Gram staining was employed
      for investigation of all colonies. The cultured P. acnes were detected by 16S
      rRNA-based polymerase chain reaction (PCR). MCs of baseline MRI were evaluated.
      RESULTS: In this study, 120 subjects (69 male and 51 female) with mean age of
      43.15 +/- 12.62 years were investigated. Sixty disc samples and eight muscle
      samples were positive for microorganisms. Moreover, 16S rDNA gene was identified
      in 46 (38.3%) disc samples. Moreover, 36/46 patients with P. acnes in their
      sample had MCs. CONCLUSION: According to the results and presence of 36/46 MCs in
      patients with lumbar disc herniation, positive for P. acnes suggests that P.
      acnes can lead to edema on the vertebrae endplates near to infected area.

PMID- 27885472
TI  - A prospective randomized trial comparing anterior cervical discectomy and fusion
      versus plate-only open-door laminoplasty for the treatment of spinal stenosis in
      degenerative diseases.
AB  - OBJECTIVE: For three or more involved cervical levels, there is a debate over
      which approach yields the best outcomes for the treatment of multilevel cervical
      degenerative disease. Our objective is to compare the radiological and clinical
      outcomes of two treatments for multilevel cervical degenerative disease: anterior
      cervical discectomy and fusion (ACDF) versus plate-only open-door laminoplasty
      (laminoplasty). METHODS: Patients were randomized on a 1:1 randomization schedule
      with 17 patients in the ACDF group and 17 patients in the laminoplasty group.
      Clinical outcomes were assessed by a visual analog scale (VAS), Japanese
      Orthopedic Association (JOA) scores, operative time, blood loss, rates of
      complications, drainage volume, discharge days after surgery, and complications.
      The cervical spine curvature index (CI) and range of motion (ROM) were assessed
      with radiographs. RESULTS: The mean VAS score, the mean JOA score, and the rate
      of complications did not differ significantly between groups. The laminoplasty
      group had greater blood loss, a longer operative time, more drainage volume, and
      a longer hospital stay than the ACDF group. There were no significant differences
      in the CI and ROM between the two groups at baseline and at each follow-up time
      point. ROM in both groups decreased significantly after surgery. CONCLUSIONS:
      Both ACDF and laminoplasty are effective and safe treatments for multilevel
      cervical degenerative disease. ACDF causes fewer traumas than laminoplasty.

PMID- 27885475
TI  - Erratum to: Validity and responsiveness of the French version of the Orebro
      Musculoskeletal Pain Screening Questionnaire in chronic low back pain.

PMID- 27885473
TI  - The application of a new type of titanium mesh cage in hybrid anterior
      decompression and fusion technique for the treatment of continuously three-level
      cervical spondylotic myelopathy.
AB  - PURPOSE: To evaluate the efficacy and safety of a new type of titanium mesh cage
      (NTMC) in hybrid anterior decompression and fusion method (HDF) in treating
      continuously three-level cervical spondylotic myelopathy (TCSM). METHODS: Ninety
      four cases who had TCSM and accepted the HDF from Jan 2007 to Jan 2010 were
      included. Clinical and radiological outcomes were compared between cases who had
      the NTMC (Group A, n = 45) and traditional titanium mesh cage (TTMC, Group B, n =
      49) after corpectomies. Each case accepted one polyetheretherketone cage (PEEK)
      after discectomy. RESULTS: Mean follow-up were 74.4 and 77.3 months in Group A
      and B, respectively (p > 0.05). Differences in cervical lordosis (CL), segmental
      lordosis (SL), anterior segmental height (ASH) and posterior segmental height
      (PSH) between two groups were not significant preoperatively, 3-days
      postoperatively or at final visit. However, losses of the CL, SL, ASH and PSH
      were all significantly larger in Group B at the final visit, so did incidences of
      segmental subsidence and severe subsidence. Difference in preoperative Japanese
      Orthopedic Association (JOA), visual analog scale (VAS), neck disability index
      (NDI) or SF-36 between two groups was not significant. At the final visit, fusion
      rate, JOA, and SF-36 were all comparable between two groups, but the VAS and NDI
      were both significantly greater in Group B. CONCLUSIONS: For cases with TCSM, HDF
      with the NTMC and TTMC can provide comparable radiological and clinical
      improvements. But application of the NTMC in HDF is of advantages in decreasing
      the subsidence incidence, losses of lordosis correction, VAS and NDI.

PMID- 27885474
TI  - Comparison of MRI-defined back muscles volume between patients with ankylosing
      spondylitis and control patients with chronic back pain: age and spinopelvic
      alignment matched study.
AB  - PURPOSE: To compare MRI-defined back muscle volume between AS patients and age,
      and spinopelvic alignment matched control patients with chronic back pain.
      METHODS: 51 male patients with AS were enrolled. Age and spinopelvic alignment
      matched controls (male) were found among non-AS patients with chronic back pain.
      After matching procedure, fully matched controls were found in 31 of 51 AS
      patients (60.8%), who represent AS patients without deformity. However, matched
      controls were not found in 20 of 51 AS patients (39.2%), who represent AS
      patients with deformity. MRI parameters of back muscle (paraspinal muscle and
      psoas muscle) at L4/5 disc level including cross-sectional area (CSA) and fat
      free cross-sectional area (FCSA) were compared between AS patients and matched
      controls. Covariates, including BMI, self-reported physical activity, and the
      presence of chronic disease, which can influence back muscle volume, were also
      investigated. RESULTS: There were no statistical differences in age, body mass
      index, score of back pain (NRS), and spinopelvic alignment, and physical activity
      between matched AS patients and control patients except for duration of back
      pain. All MRI parameters for paraspinal muscle volume in matched AS patients
      (without deformity) were significantly less than those of control patients, and
      significantly larger than those of non-matched AS patients (with deformity). Body
      size adjusted MRI parameters (relative CSA and relative FCSA) of paraspinal
      muscle showed strong correlations with lumbar lordosis and sacral slope. Such
      relationship between paraspinal muscle and spinopelvic parameters remained
      significant even after multivariate adjustment. CONCLUSIONS: AS patients without
      deformity already have decreased paraspinal muscle volume compared with age and
      spinopelvic alignment matched non-AS patients with chronic back pain. Such
      decrease in paraspinal muscle volume was significantly associated with kyphotic
      deformity of AS patients even after multivariate adjustment. Although the result
      of our study supports the causal relationship between muscle degeneration and
      kyphotic deformity in AS patients, further study is required to prove the
      causality.

PMID- 27885476
TI  - Does T2 mapping of the posterior annulus fibrosus indicate the presence of lumbar
      intervertebral disc herniation? A 3.0 Tesla magnetic resonance study.
AB  - PURPOSE: Indicating lumbar disc herniation via magnetic resonance imaging (MRI)
      T2 mapping in the posterior annulus fibrosus (AF). METHODS: Sagittal T2 maps of
      313 lumbar discs of 64 patients with low back pain were acquired at 3.0 Tesla
      (3T). The discs were rated according to disc herniation and bulging. Region of
      interest (ROI) analysis was performed on median, sagittal T2 maps. T2 values of
      the AF, in the most posterior 10% (PAF-10) and 20% of the disc (PAF-20), were
      compared. RESULTS: A significant increase in the T2 values of discs with
      herniations affecting the imaged area, compared to bulging discs and discs with
      lateral herniation, was shown in the PAF-10, where no association to the NP was
      apparent. The PAF-20 exhibited a moderate correlation to the nucleus pulposus
      (NP). CONCLUSIONS: High T2 values in the PAF-10 suggest the presence of disc
      herniation (DH). The results indicate that T2 values in the PAF-20 correspond
      more to changes in the NP.

PMID- 27885478
TI  - The Roland-Morris Disability Questionnaire: one or more dimensions?
AB  - PURPOSE: The Roland-Morris Disability Questionnaire (RMDQ) is one of the most
      recommended questionnaires to assess disability. Some previous studies support
      the assumption that the RMDQ is a unidimensional measure; however, recent studies
      have suggested that this measure has more than one domain and should be
      considered as a multidimensional scale. Therefore, the aim of this study was to
      analyse the structure of the RMDQ in a large sample of patients with low back
      pain using two different statistical approaches. METHODS: We analysed existing
      datasets from previous clinical studies. We assessed unidimensionality using
      Rasch analysis of item fit statistics and through principle component analysis of
      residuals. We also performed confirmatory factor analysis (CFA) to test the
      hypothesis of a 3-factor solution. RESULTS: We included data from 2826 patients
      with non-specific low back pain. The average age of all participants included was
      46.4 years, and half of the participants were women (50.1%). The Rasch analysis
      model showed that the RMDQ is unidimensional, with only two items demonstrating
      slight excessive positive outfit. Results from the CFA suggested poor fit to the
      data of a 3-factor solution. CONCLUSIONS: We recommend that the RMDQ should still
      be used as a unidimensional scale for measuring disability as the only construct.

PMID- 27885477
TI  - Impact of old age on patient-report outcomes and cost utility for anterior
      cervical discectomy and fusion surgery for degenerative spine disease.
AB  - PURPOSE: With growing older population and increasing rates of cervical spinal
      surgery, it is vital to understand the value of cervical surgery in this
      population. We set forth to determine the cost utility following anterior
      cervical decompression and fusion (ACDF) for degenerative disease in older
      patients. METHODS: Patients undergoing ACDF for degenerative diseases were
      enrolled into prospective longitudinal registry. Patient-reported outcomes (PROs)
      were recorded at baseline, 1-year, and 2-year postoperatively. Two-year medical
      resource utilization, missed work, and health-state values [quality-adjusted life
      years (QALYs)] were assessed to compute cost per QALY gained. Patients were
      dichotomized based on age: <65 years (younger) and >=65 years (older) to compare
      the cost utility in these age groups. RESULTS: Total 218 (87%) younger patients
      and 33 (13%) older patients who underwent ACDF were analyzed. Both the groups
      demonstrated a significant improvement in PROs 2-year following surgery. The
      older patients had a lower mean cumulative gain in QALYs compared to younger
      patients at 1 year (0.141 vs. 0.28, P = 0.05) and 2 years (0.211 vs. 0.424, P =
      0.04). There was no significant difference in the mean total 2-year cost between
      older [$21,041 (95% CI $18,466-$23,616)] and younger [$22,669 (95% CI $$21,259
      $24,079)] patients (P = 0.27). Two-year cost per QALY gained in older vs. younger
      patients was ($99,720/QALYs gained vs. ($53,464/QALYs gained, P = 0.68).
      CONCLUSION: ACDF surgery provided a significant gain in health-state utility in
      older patients with degenerative cervical pathology, with a mean cumulative 2
      year cost per QALY gained of $99,720/QALY. While older patients have a slightly
      higher cost utility compared to their younger counterparts, surgery in the older
      cohort does provide a significant improvement in pain, disability, and quality-of
      life outcomes.

PMID- 27885479
TI  - Wait and see approach for rectal cancer with a clinically complete response after
      neoadjuvant concurrent chemoradiotherapy.
AB  - PURPOSE: Rectal cancer patients with a pathological complete response (pCR) after
      neoadjuvant concurrent chemoradiotherapy (CCRT) have a better prognosis compared
      to those without a pCR. Therefore, the "Wait and See" (W&S) approach in those who
      achieved clinically complete response (cCR) after CCRT was introduced as an
      alternative modality to the total mesorectal excision (TME). The aim of this
      study was to compare the oncological outcomes between W&S and TME via meta
      analysis. METHODS: We performed a comprehensive literature search on January 14,
      2016, using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials,
      Web of Science, and Scopus. In addition, the references of all articles obtained
      were searched manually. The qualities of each study were assessed using the
      Newcastle-Ottawa quality assessment scale. The main outcomes were recurrence,
      disease-free survival (DFS), and overall survival (OS). We calculated the risk
      ratio (RR) and hazard ratio (HR) for the recurrence and survival rates,
      respectively. RESULTS: The RR of patients whose initial recurrences was local
      recurrence (LR), distant metastasis (DM), LR + DM, or overall recurrences were
      0.18, 1.00, 0.61, and 0.49, respectively. There was no heterogeneity in the
      results. The HR of DFS was 0.59 and indicated that DFS in the TME group was
      superior compared with that in the W&S group. The OS has no significant
      difference between the studies. CONCLUSIONS: Although the W&S approach seemed
      feasible for rectal cancer patients with a cCR after neoadjuvant CCRT, concrete
      evidence obtained in well-controlled randomized trials with a long-term follow-up
      is required to validate potential treatment options.

PMID- 27885480
TI  - A single institution's long-term follow-up of patients with pathological complete
      response in locally advanced rectal adenocarcinoma following neoadjuvant
      chemoradiotherapy.
AB  - PURPOSE: This paper aimed to study the long term follow-up of patients with
      primary rectal adenocarcinoma receiving neoadjuvant chemoradiotherapy who
      obtained a pathological complete response (pCR) and identify factors predicting
      complete response. METHODS: Retrospective review of notes, histology, pre
      operative full blood count and imaging of patients with primary rectal
      adenocarcinoma diagnosed in our institute from 2000 to 2012 from a prospectively
      maintained database were used. SPSS version 22.0 was used for statistical
      analysis. RESULTS: Three hundred eighty patients diagnosed with primary rectal
      adenocarcinoma were identified, 277 received neoadjuvant chemoradiotherapy
      followed by curative resection. Forty-six patients obtained a pCR (ypT0N0) with
      no local recurrence and two metastatic recurrences on follow-up. Patients with a
      pCR have a significantly improved overall survival and disease-free survival
      compared to a non-pCR (150.0 and 136.1 vs 77.5 and 84.7 months, p = 0.001). On
      univariate analysis, increased tumour height above anal verge, low lymph node
      yield, high pre-operative haemoglobin and a low neutrophil-lymphocyte ratio are
      significant factors identifying a pCR. Multivariable analysis of the above
      factors confirmed tumour height above anal verge as significant in obtaining a
      pCR. CONCLUSION: Patients with rectal adenocarcinoma who develop a pCR following
      neoadjuvant chemoradiotherapy have improved overall and disease-free survival. We
      have identified distance from anal verge, low lymph node yield, high pre
      operative haemoglobin and low neutrophil-lymphocyte ratio as significant
      predictors of developing a pCR.

PMID- 27885482
TI  - Traveling through the perineum(s): to the discovery of an old world.
AB  - INTRODUCTION: The migration of large numbers of people and refugees induces
      various fears in their receiving countries; the arrival of potential terrorists,
      and, among others, the negative impact that their need for health care can have
      on the sustainability of health services. In this sense, migrants are considered
      by many a threat. METHOD: In this brief "letter narrative", based on the
      experience gained in the treatment of various diseases of the perineum, I mean to
      suggest that the perineal disorders, especially in women, is common event, shared
      by women of different ethnicity, culture, and religion. Moreover, they do not
      threaten the sustainability of health services. DICUSSION AND CONCLUSION: For the
      scientific community, there is a need for greater attention and conscious
      analysis of pathologies and fundamental human rights that accompany these
      populations to better understand the scope and value also in terms of scientific
      research in this epochal event.

PMID- 27885481
TI  - Post-operative recurrence of Crohn's disease after definitive stoma: an
      underestimated risk.
AB  - INTRODUCTION: Crohn's disease (CD) is a progressive inflammatory disease
      affecting the entire gastrointestinal tract. The need for a definitive stoma (DS)
      is considered as the ultimate phase of damage. It is often believed that the risk
      of further disease progression is small when a DS has been performed. AIMS: The
      goals of the study were to establish the rate of CD recurrence above the DS and
      to identify predictive factors of CD recurrence at the time of DS. METHODS: We
      retrospectively reviewed all medical records of consecutive CD patients having
      undergone DS between 1973 and 2010. We collected clinical data at diagnosis, CD
      phenotype, treatment, and surgery after DS and mortality. Stoma was considered as
      definitive when restoration of continuity was not possible due to proctectomy,
      rectitis, anoperineal lesions (APL), or fecal incontinence. Clinical recurrence
      (CR) was defined as the need for re-introduction or intensification of medical
      therapy, and surgical recurrence (SR) was defined as a need for a new intestinal
      resection. RESULTS: Eighty-three patients (20 males, 63 females) with a median
      age of 34 years at CD diagnosis were included. The median time between diagnosis
      and DS was 9 years. The median follow-up after DS was 10 years. Thirty-five
      patients (42%) presented a CR after a median time of 28 months (2-211) and 32
      patients (38%) presented a SR after a median time of 29 months (4-212). In a
      multivariate analysis, APL (HR = 5.1 (1.2-21.1), p = 0.03) and colostomy at time
      of DS (HR = 3.8 (1.9-7.3), p = 0.0001) were associated factors with the CR.
      CONCLUSION: After DS for CD, the risk of clinical recurrence was high and
      synonymous with surgical recurrence, especially for patients with APL and
      colostomy.

PMID- 27885483
TI  - Neuroborreliosis.
AB  - Appropriate, critical application of evidence-based diagnostic criteria enables
      both a clear definition of what constitutes neuroborreliosis-nervous system
      infection with Borrelia burgdorferi sensu stricto in the US, B garinii and less
      commonly B. afzelii and other species in Europe-and recognition that this
      disorder is quite similar in Europe and the US. Most commonly evidenced by
      lymphocytic meningitis and/or multifocal inflammation of the peripheral (common;
      cranial neuropathy, radiculopathy, mononeuropathy multiplex) or central (rare)
      nervous system, it is readily diagnosed and highly antibiotic responsive.
      Encephalopathy-altered cognition or memory-can occur as part of the systemic
      infection and inflammatory state, but is not evidence of neuroborreliosis. Post
      treatment Lyme disease syndrome-persistent neurobehavioral symptoms 6 months or
      more after usually curative antibiotic treatment-if real and not simply an
      example of anchoring bias-is unrelated to neuroborreliosis. The pathophysiology
      of neuroborreliosis remains unclear, but appears to involve both a requirement
      for viable micro-organisms and significant immune amplification.

PMID- 27885485
TI  - Heinrich Simon Frenkel (1860-1931).

PMID- 27885484
TI  - The impact of cerebral microbleeds on intracerebral hemorrhage and poor
      functional outcome of acute ischemic stroke patients treated with intravenous
      thrombolysis: a systematic review and meta-analysis.
AB  - It is still controversial whether pre-existing cerebral microbleeds (CMBs)
      increase the risks of intracranial hemorrhage (ICH) and poor functional outcome
      (PFO) in acute ischemic stroke (AIS) patients treated with intravenous
      thrombolysis (IVT). Therefore, we performed a systematic review and meta-analysis
      to determine the impact of CMBs on ICH and PFO of AIS patients with IVT. We
      searched PubMed, EMBASE and Web of Science from inception to August 3, 2016, with
      language restriction in English. We included studies that reported the
      relationship between CMBs and ICH or PFO after thrombolysis. Two retrospective
      and nine prospective studies met inclusion criteria (total 2702 patients). The
      overall prevalence of CMBs on pre-IVT MRI scans was 24.0%. Pre-existing CMBs on
      MRI scans were not significantly associated with a higher risk of early sICH (OR
      1.74; 95% CI 0.91-3.33; I 2 = 44.5%). Subgroup analyses did not substantially
      influence these associations. The presence of CMBs was associated with the
      increased risk of 3-month PFO (OR 1.58; 95% CI 1.08-2.31; I 2 = 54.2%), PH (OR
      2.14; 95% CI 1.34-3.42; I 2 = 11.0%) and any ICH (OR 1.42; 95% CI 1.04-1.95; I 2
      = 0.0%), respectively. This meta-analysis showed that CMBs presence was not
      significantly associated with the increased risk of early sICH after IVT.
      However, the results also demonstrated that CMBs presence increased the risks of
      3-month PFO, PH and any ICH after IVT. Due to a small number of included studies
      and methodological limitations, the results of this meta-analysis should be
      interpreted cautiously. CMBs presence should not be a contraindication to IVT for
      AIS patients based on the existing evidence.

PMID- 27885487
TI  - Molecular Analysis of the CTNS Gene in Indians with Nephropathic Cystinosis.

PMID- 27885486
TI  - Pathological laughter as onset symptom in atypical parkinsonisms.

PMID- 27885488
TI  - Claudins in viral infection: from entry to spread.
AB  - Tight junctions are critically important for many physiological functions,
      including the maintenance of cell polarity, regulation of paracellular
      permeability, and involvement in signal transduction pathways to regulate
      integral cellular processes. Furthermore, tight junctions enable epithelial cells
      to form physical barriers, which act as an innate immune mechanism that can
      impede viral infection. Viruses, in turn, have evolved mechanisms to exploit
      tight junction proteins to gain access to cells or spread through tissues in an
      infected host. Claudin family proteins are integral components of tight junctions
      and are thought to play crucial roles in regulating their permeability. Claudins
      have been implicated in the infection process of several medically important
      human pathogens, including hepatitis C virus, dengue virus, West Nile virus, and
      human immunodeficiency virus, among others. In this review, we summarize the role
      of claudins in viral infections and discuss their potential as novel antiviral
      targets. A better understanding of claudins during viral infection may provide
      insight into physiological roles of claudins and uncover novel therapeutic
      antiviral strategies.

PMID- 27885491
TI  - Erratum to: nab-Paclitaxel Plus Gemcitabine Versus Gemcitabine in Patients with
      Metastatic Pancreatic Adenocarcinoma: Canadian Subgroup Analysis of the Phase 3
      MPACT Trial.

PMID- 27885492
TI  - Polymorphism of growth hormone receptor (GHR) gene in Nilagiri sheep.
AB  - The allelic variation in the regulatory sequence of growth hormone receptor (GHR)
      gene influences the growth traits of sheep. A study was carried out to find out
      the polymorphisms associated with exon 10 of GHR gene and its association with
      growth traits of Nilagiri sheep. The blood samples were collected from Nilagiri
      sheep (n = 103) reared at Sheep Breeding Research Station, Sandynallah, Tamil
      Nadu, India. DNA was isolated using the phenol-chloroform extraction procedure
      and eight samples having amplified product of part of exon 10 (895 bp) sequenced.
      The results indicated transitions of nucleotide G>A at loci G177624A and
      G177878A. The genotyping frequencies estimated using the tetra-primer
      amplification refractory mutation system-PCR for GG, GA and AA were 0.262, 0.544
      and 0.194, and 0.349, 0.505 and 0.146, respectively. The estimated allele
      frequencies of G and A nucleotides were 0.5340 and 0.4660, and 0.6015 and 0.3985,
      respectively, at loci G177624A and G177878A. The effects of both the mutations on
      growth-related traits viz., birth, weaning (3 months) 6, 9 and 12 months weight
      in Nilagiri sheep were found to be non-significant. This can be a novel approach
      to assess growth of sheep using the mutation in GHR gene. Thus, this approach can
      be useful for further investigation as a molecular marker associated with genetic
      improvement.

PMID- 27885490
TI  - Localized cortical chronic traumatic encephalopathy pathology after single,
      severe axonal injury in human brain.
AB  - Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated
      with repetitive mild impact traumatic brain injury from contact sports. Recently,
      a consensus panel defined the pathognomonic lesion for CTE as accumulations of
      abnormally hyperphosphorylated tau (p-tau) in neurons (neurofibrillary tangles),
      astrocytes and cell processes distributed around small blood vessels at sulcal
      depths in irregular patterns within the cortex. The pathophysiological mechanism
      for this lesion is unknown. Moreover, a subset of CTE cases harbors cortical beta
      amyloid plaques. In this study, we analyzed postmortem brain tissues from five
      institutionalized patients with schizophrenia and history of surgical leucotomy
      with subsequent survival of at least another 40 years. Because leucotomy involves
      severing axons bilaterally in prefrontal cortex, this surgical procedure
      represents a human model of single traumatic brain injury with severe axonal
      damage and no external impact. We examined cortical tissues at the leucotomy site
      and at both prefrontal cortex rostral and frontal cortex caudal to the leucotomy
      site. For comparison, we analyzed brain tissues at equivalent neuroanatomical
      sites from non-leucotomized patients with schizophrenia, matched in age and
      gender. All five leucotomy cases revealed severe white matter damage with dense
      astrogliosis at the axotomy site and also neurofibrillary tangles and p-tau
      immunoreactive neurites in the overlying gray matter. Four cases displayed p-tau
      immunoreactivity in neurons, astrocytes and cell processes encompassing blood
      vessels at cortical sulcal depths in irregular patterns, similar to CTE. The
      three cases with apolipoprotein E epsilon4 haplotype showed scattered beta
      amyloid plaques in the overlying gray matter, but not the two cases with
      apolipoprotein E epsilon3/3 genotype. Brain tissue samples from prefrontal cortex
      rostral and frontal cortex caudal to the leucotomy site, and all cortical samples
      from the non-leucotomized patients, showed minimal p-tau and beta-amyloid
      pathology. These findings suggest that chronic axonal damage contributes to the
      unique pathology of CTE over time.

PMID- 27885493
TI  - Hepatic encephalopathy: present and future.

PMID- 27885495
TI  - Erratum to: Prognostic value of right ventricular free wall strain in pulmonary
      hypertension patients with pseudo-normalized tricuspid annular plane systolic
      excursion values.

PMID- 27885494
TI  - Comparison of arterial stiffness/compliance in the ascending aorta and common
      carotid artery in healthy subjects and its impact on left ventricular structure
      and function.
AB  - Arterial stiffness and compliance parameters from two adjacent elastic arteries
      [aorta and common carotid artery (CCA)] were compared and their relationship with
      left ventricular (LV) structure and function and clinical parameters was
      assessed. 584 healthy subjects were prospectively enrolled [mean age 47.8 +/-
      18.4 years, range 16-94; 318 (54.4%) men]. They underwent comprehensive
      transthoracic echocardiography; M-mode diameters were measured at the level of
      the ascending aorta in systole and diastole and by echo-tracking at the level of
      the left CCA. The beta-stiffness, pressure-strain elastic modulus, arterial
      compliance and one-point pulse wave velocity were derived. A significant
      correlation was observed between aortic and CCA stiffness and compliance
      parameters (p < 0.0001 for all). At multiple regression analysis, CCA stiffness
      parameters were constantly correlated with age and systolic blood pressure, and
      accounted for up to 56% of the variability (vs. only 29% in aortic stiffness and
      compliance). CCA stiffness parameters were found to better predict LV structure,
      diastolic function than aortic stiffness parameters. Aortic and CCA stiffness and
      compliance were found to correlate with each other and with age, with the
      correlation being higher for CCA stiffness. At multiple regression analysis, CCA
      stiffness parameters were better predictors of LV structure and function than
      aortic stiffness.

PMID- 27885496
TI  - Descending aortic mechanics and atrial fibrillation: a two-dimensional speckle
      tracking transesophageal echocardiography study.
AB  - Vascular mechanics assessed with two-dimensional speckle tracking
      echocardiography (2D-STE) could be used as a new imaging surrogate of vascular
      stiffening. The CHA2DS2-VASc score is considered accurate as an estimate of
      stroke risk in non-valvular AF, although many potential stroke risk factors have
      not been included in this scoring method. The purpose of this research is to
      study the feasibility of evaluating vascular mechanics at the descending aorta in
      non-valvular AF patients using transesophageal 2D-STE and to analyze the
      association between descending aortic mechanics and stroke. We prospectively
      recruited a group of 44 patients referred for a transesophageal echocardiogram
      (TEE) in the context of cardioversion for non-valvular AF. A short-axis view of
      the descending aorta, one to two centimeters after the aortic arch was selected
      for the vascular mechanics assessment with the 2D-STE methodology. The vascular
      mechanics parameters analyzed were circumferential aortic strain (CAS) and early
      circumferential aortic strain rate (CASR). A clinical assessment was performed
      with focus on the past stroke history and the CHA2DS2-VASc score. The mean age of
      our cohort was 65 +/- 13 years and 75% were men; AF was known for 2.8 +/- 2.5
      years and it was considered paroxystic in 41% of cases. Waveforms adequate for
      measuring 2D-STE were present in 85% of the 264 descending aortic wall segments.
      The mean CAS was 3.5 +/- 1.2% and the mean CASR was 0.7 +/- 0.3 s-1. The inter-
      and intra-observer variability for aortic mechanics was considered adequate. The
      median CHA2DS2VASc score was 2 (2-3). As the score increased we noted that both
      the CAS (r = -0.38, P = 0.01) and the CASR (r = -0.42, P < 0.01) decreased. Over
      16% of the AF patients had a past history of stroke. These patients had lower
      values of both descending aortic strain [2.2 (1.8-2.6) vs. 3.9 (3.3-4.9)%, P <
      0.01] and strain rate [0.4 (0.3-0.4) vs. 0.7 (0.6-1.1) s-1, P < 0.01]. CAS
      remained independently associated with a past history of stroke after adjustment
      for the CHA2DS2VASc score. Our data showed that non-valvular AF patients with a
      past history of stroke had lower values of aortic mechanics assessed with
      transesophageal 2D-STE.

PMID- 27885497
TI  - Erratum to: A zebrafish mosaic assay to study mammalian stem cells in real time
      in vivo.

PMID- 27885499
TI  - The effects of alpha 1-adrenoceptor blockade and angiotensin converting enzyme
      inhibition on central and brachial blood pressure and vascular reactivity: the
      doxazosin-ramipril study.
AB  - We aimed to study whether inhibition of the renin-angiotensin-aldosterone system
      has effects on vascular structure and function beyond the effects on blood
      pressure reduction alone. Patients with mild-to-moderate hypertension (n = 61,
      age 54 +/- 12 years, 34% women) received the angiotensin converting enzyme
      inhibitor ramipril 10 mg or the alpha 1-adrenoceptor blocker doxazosin 8 mg
      double-blind for 12 weeks. Aortic blood pressure, pulse wave velocity, and
      augmentation index were assessed by applanation tonometry. Endothelial function
      was studied by forearm post-ischemic flow mediated vasodilatation and by pulse
      wave analysis with beta 2-adrenoceptor agonist stimulation. Skin microvascular
      reactivity was assessed by laser Doppler fluxmetry and iontophoresis. Treatment
      with doxazosin or ramipril reduced aortic and brachial blood pressures (all P <
      0.001), with greater reductions in aortic than brachial systolic blood pressures
      (P = 0.021) and aortic/brachial pulse pressure ratio (P = 0.005). Compared to
      doxazosin, ramipril reduced carotid-femoral and carotid-radial pulse wave
      velocity (both P < 0.05). Forearm endothelial dependent and independent
      vasodilatation, assessed by post-ischemic flow mediated vasodilatation and
      glyceryl trinitrate, and by pulse wave analysis remained unchanged by both
      doxazosin and ramipril. In addition, skin microvascular endothelial dependent
      (acetylcholine) and independent vasodilatation (sodium nitroprusside) remained
      unchanged. In conclusion, ramipril reduced indices of aortic stiffness,
      suggesting that angiotensin converting enzyme inhibitor therapy may have effects
      beyond blood pressure reduction. However, treatment did not appear to influence
      endothelial function. Evidence of endothelial dysfunction and its possible
      improvement by antihypertensive treatment might require more advanced
      hypertension.This study is registered at ClinicalTrials.gov (NCT02901977) and at
      EudraCT (# 2007-000631-25).

PMID- 27885498
TI  - Prognostic predictive value of gene mutations in Japanese patients with
      hypertrophic cardiomyopathy.
AB  - Although some studies have attempted to find useful prognostic factors in
      hypertrophic cardiomyopathy (HCM), those results are not fully helpful for use in
      actual clinical practice. Furthermore, several genetic abnormalities associated
      with HCM have been identified. However, the genotype-phenotype correlation in HCM
      remains to be elucidated. Here, we attempted to assess patients with different
      types of gene mutations causing HCM and investigate the prognosis. A total of 140
      patients with HCM underwent a screening test for myofilament gene mutations by
      direct sequencing of eight sarcomeric genes. Patients with a single mutation in
      cardiac troponin T, cardiac troponin I, alpha-tropomyosin, and regulatory and
      essential light chains were excluded from the study because the number of cases
      was too small. The clinical presentations and outcomes of the remaining 127
      patients with HCM, 31 beta-myosin heavy chain (MYH7) mutation carriers, 19
      cardiac myosin-binding protein C (MYBPC3) mutation carriers, and 77 mutation non
      carriers were analyzed retrospectively. MYBPC3 mutation carriers had a high
      frequency of ventricular arrhythmia and syncope. Kaplan-Meier curves revealed no
      significant difference in prognosis among the three groups, but a lack of family
      history of sudden death (SD) and a past history of syncope were significantly
      related to poor prognosis. An absence of family history of SD and past history of
      syncope are useful prognostic factors in patients with HCM. MYH7 and MYBPC3
      mutations did not significantly influence prognosis compared to non-carriers.
      However, patients with the MYBPC3 mutation should be closely followed for the
      possibility of SD.

PMID- 27885500
TI  - A review of anaesthetic outcomes in patients with genetically confirmed
      mitochondrial disorders.
AB  - : Mitochondrial disorders are a clinically and biochemically diverse group of
      disorders which may involve multiple organ systems. General anaesthesia (GA)
      poses a potential risk of decompensation in children with mitochondrial
      disorders, and there is little guidance for anaesthetists and other clinicians
      regarding the optimal anaesthetic agents and perioperative management to provide
      to patients with mitochondrial disease[15]. The aim of this review was to
      document adverse events and perioperative complications from GA in patients with
      genetically confirmed mitochondrial disorders. A retrospective chart review of
      patients with genetically confirmed mitochondrial disorders who had undergone GA
      was undertaken. The indication for GA, anaesthetic agents utilised, length of
      admission and post anaesthetic complications were documented and analysed. Twenty
      six patients with genetically proven mitochondrial disease underwent 65 GAs.
      Thirty-four (52%), received propofol as their induction agent. Thirty-three (51%)
      patients received sevoflurane for the maintenance of anaesthesia, while 8 (12%)
      received isoflurane and 24 (37%) received propofol. The duration of most GAs was
      short with 57 (87%) lasting less than 1 h. Perioperative complications occurred
      in five patients while under GA including ST segment depression, hypotension and
      metabolic acidosis in one. All five patients were stabilised successfully and
      none required ICU admission as a consequence of their perioperative
      complications. The duration of hospital stay post GA was <24 h in 25 (38%)
      patients. CONCLUSION: No relationship between choice of anaesthetic agent and
      subsequent perioperative complication was observed. It is likely that individual
      optimisation on a case-by-case basis is more important overall than choice of any
      one particular technique. What is Known: * General anaesthesia (GA) poses a
      potential risk of decompensation in children with mitochondrial disorders. *
      There is a great diversity in the anaesthetic approaches undertaken in this
      cohort, and little guidance exists for anaesthetists and other clinicians
      regarding the optimal anaesthetic agents and perioperative management to provide
      to patients with mitochondrial disease. What is New: * In this study of 26
      patients with genetically confirmed mitochondrial disease who underwent 65 GAs,
      no relationship between choice of anaesthetic agent and subsequent perioperative
      complication was observed * It is likely that individual optimisation on a case
      by-case basis is more important overall than choice of any one particular
      technique.

PMID- 27885501
TI  - Valence of Affective Verbal Fluency: fMRI Studies on Neural Organization of
      Emotional Concepts Joy and Fear.
AB  - The present study was designed to examine the underlying brain mechanisms of
      positive and negative emotional verbal fluency. Three verbal fluency tasks (one
      non-emotional phonemic task, two emotional tasks: Joy and Fear) were used in this
      study. The results were analyzed for 35 healthy, Polish-speaking, right-handed
      adults aged 20-35. Functional magnetic resonance imaging (3T) was used to show
      brain activity during active participation in emotional verbal fluency tasks. The
      results reported for emotional fluency confirmed activation of different brain
      regions for the negative and positive emotional verbal fluency: in positive
      emotional verbal fluency Joy elicits greater activation in the frontal regions
      and the cingulate cortex, while in negative verbal fluency Fear is reflected in
      activation of parietal and temporal areas. The study provides an evidence for
      differentiation in neural mechanisms between positive and negative emotional
      verbal fluency and/or positive and negative retrieving processes, and
      differentiation in brain-related determinants of the emotional concepts
      organization.

PMID- 27885502
TI  - Fading of wound-induced volatile release during Populus tremula leaf expansion.
AB  - The release of stress-driven volatiles throughout leaf development has been
      little studied. Therefore, we subjected poplar leaves during their developmental
      stage (from 2 days to 2 weeks old) to wounding by a single punch hole, and
      measured online the wound-induced volatile organic compound emissions. Our study
      shows that the emission of certain volatile compounds fades with increasing leaf
      age. Among these compounds we found lipoxygenase products (LOX products),
      acetaldehyde, methyl benzoate, methyl salicylate, and mono- and sesquiterpenes.
      In parallel, we studied the fading of constitutive emissions of methanol during
      leaf maturation, as well as the rise in isoprene constitutive emission during
      leaf maturation and its relationship to leaf photosynthetic capacity. We found
      highly significant relationships between leaf chlorophyll content, photosynthetic
      capacity, and leaf size during leaf ageing. As the level of constitutive defences
      increases with increasing leaf age, the strength of the volatile signal is
      expected to be gradually reduced. The higher elicitation of volatile organic
      compound emissions (especially LOX products) in younger leaves could be an
      evolutionary defence against herbivory, given that younger leaves are usually
      more subjected to infestation and herbivory.

PMID- 27885503
TI  - Shoot density of Miscanthus sinensis populations in different habitats and their
      maintenance mechanisms in relation to shoot growth.
AB  - How perennial grass populations are maintained in different climates is poorly
      understood at the level of individual shoots (ramets). During the years 1982-1987
      and 1991-1993, measurements of shoot dynamics and growth in populations of a
      clonal grass, Miscanthus sinensis, were made at two sites in Japan that differed
      by approximately 5  degrees C in mean temperature. While annual shoot births were
      very stable during the period 1982-1987 at both sites, the number of flowering
      shoots fluctuated cyclically every year. The clonal propagation of shoots was
      size-independent, whereas the reproduction (flowering) of shoots was size
      dependent and negatively affected their own offspring size. Shoot size negatively
      affected the overwintering of shoots. In the warm climate with a long growing
      period (9 months), both early-emerging shoots and the subsequent high order
      tillering shoots developed in large numbers. In the cool climate with a short
      growing period (6 months), more than half of the annual births occurred in August
      and September. Nevertheless, average longevity and wintering competency of shoots
      were not greatly different between the two populations. In response to a warmer
      climate, tillerings started earlier. This appeared to increase the total number
      of new shoots that would die within the year; nevertheless, the shoot densities
      remained much higher because a longer growing season would increase the number of
      high order tillerings. There was thus a trade-off between the annual survival
      ratio of new shoots and the number of annual shoot births.

PMID- 27885504
TI  - Plant dicer-like proteins: double-stranded RNA-cleaving enzymes for small RNA
      biogenesis.
AB  - Dicer, a double-stranded RNA (dsRNA)-specific endoribonuclease, plays an
      essential role in triggering both transcriptional and post-transcriptional gene
      silencing in eukaryotes by cleaving dsRNAs or single-stranded RNAs bearing stem
      loop structures such as microRNA precursor transcripts into 21- to 24-nt small
      RNAs. Unlike animals, plants have evolved to utilize at least four Dicer-like
      (DCL) proteins. Extensive genetic studies have revealed that each DCL protein
      participates in a specific gene silencing pathway, with some redundancy. However,
      a mechanistic understanding of how the specific action of each DCL protein is
      regulated in its respective pathway is still in its infancy due to the limited
      number of biochemical studies on plant DCL proteins. In this review, we summarize
      and discuss the biochemical properties of plant DCL proteins revealed by studies
      using highly purified recombinant proteins, crude extracts, and
      immunoprecipitates. With help from co-factor proteins and an ATPase/DExH-box RNA
      helicase domain, the microRNA-producing enzyme DCL1 recognizes bulges and
      terminal loop structures in its substrate transcripts to ensure accurate and
      efficient processing. DCL4 prefers long dsRNA substrates and requires the dsRNA
      binding protein DRB4 for its activity. The short-dsRNA preference of DCL3 is well
      suited for short-RNA transcription and subsequent dsRNA formation by coupling
      between a plant-specific DNA-dependent RNA-polymerase IV and RNA-dependent RNA
      polymerase 2 in the transcriptional gene silencing pathway. Inorganic phosphate
      also seems to play a role in differential regulation of DCL3 and DCL4 activities.
      Further development of biochemical approaches will be necessary for better
      understanding of how plant DCL proteins are fine-tuned in each small RNA
      biogenesis pathway under various physiological conditions.

PMID- 27885505
TI  - Pre-microRNA processing activity in nuclear extracts from Arabidopsis suspension
      cells.
AB  - MicroRNAs (miRNAs) play important roles in a variety of biological phenomena,
      such as development and responses to abiotic and biotic stresses, by regulating
      complementary target transcripts. Primary MIRNA transcripts (pri-miRNAs) are
      processed into miRNA/miRNA* duplexes via pre-miRNA intermediates by DICER family
      proteins. In plants miRNA/miRNA* duplexes are produced from pri-miRNAs
      exclusively by a complex containing DICER-LIKE1 (DCL1), Hyponastic leaves1 (HYL1)
      and SERREATE (SE) in the nucleus. Pri-miRNA or pre-miRNA processing activity has
      been detected using recombinant DCL1, HYL1 and SE proteins expressed in insect
      cells and immunopurified DCL1-HYL1-SE-containing complexes that transiently co
      overexpressed in Nicotiana benthamiana. However, the processing of pre-miRNAs
      into miRNA/miRNA* using nuclear extracts has not been reported. Here I report the
      detection of pre-miRNA processing in nuclear extracts prepared from Arabidopsis
      suspension cells. In the nuclear extracts including DCL1, small RNAs that were 21
      nucleotides in length were excised from a part of miRNA/miRNA* regions on pre
      miRNAs. This system is potentially useful for in vitro analyses of pre-miRNA
      processing.

PMID- 27885507
TI  - Erratum to: Genomic and functional features of the biosurfactant producing
      Bacillus sp. AM13.

PMID- 27885506
TI  - Marsh frogs, Pelophylax ridibundus, determine migratory direction by magnetic
      field.
AB  - Orientation by magnetic cues appears to be adaptive during animal migrations.
      Whereas the magnetic orientation in birds, mammals, and urodele amphibians is
      being investigated intensively, the data about anurans are still scarce. This
      study tests whether marsh frogs could determine migratory direction between the
      breeding pond and the wintering site by magnetic cues in the laboratory. Adult
      frogs (N = 32) were individually tested in the T-maze 127 cm long inside the
      three-axis Helmholtz coil system (diameter 3 m). The arms of the maze were
      positioned parallel to the natural migratory route of this population when
      measured in accordance with magnetic field. The frogs were tested under two
      motivational conditions mediated by temperature/light regime: the breeding
      migratory state and the wintering state. The frogs' choice in a T-maze was
      evident only when analyzed in accordance with the direction of the magnetic
      field: they moved along the migratory route to the breeding pond and followed the
      reversion of the horizontal component of the magnetic field. This preference has
      been detected in both sexes only in the breeding migratory state. This suggests
      that adult ranid frogs can obtain directional information from the Earth's
      magnetic field as was shown earlier in urodeles and anuran larvae.

PMID- 27885509
TI  - Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their
      structure activity relationship.
AB  - OBJECTIVES: To determine the inhibitory activities of flavonoids against NS2B-NS3
      protease of ZIKA virus (ZIKV NS2B-NS3pro) expressed in Escherichia coli BL21
      (DE3) and their structure activity relationship. RESULTS: ZIKV NS2B-NS3pro was
      expressed in E. coli BL21(DE3) as a 35 kDa protein. It had a K m of 26 uM with
      the fluorogenic peptide Dabcyl-KTSAVLQSGFRKME-Edan. The purified ZIKV NS2B-NS3pro
      was used for inhibition and kinetic assays to determine the activities of 22
      polyphenol compounds. These polyphenol compounds at 100 uM inhibited the activity
      of ZIKV NS2B-NS3pro by 6.2-88%. Seven polyphenol compounds had IC50 ranging from
      22 +/- 0.2 to 112 +/- 5.5 uM. Myricetin showed a mixed type inhibitory pattern
      against ZIKV NS2B-NS3pro protease. Its IC50 value was 22 +/- 0.2 uM with a K i
      value of 8.9 +/- 1.9 uM. CONCLUSION: The chemical structure of a polyphenol
      compound and its inhibitory activity against ZIKV NS2B-NS3pro can be explored to
      develop highly selective inhibitors against ZIKV NS2B-NS3pro.

PMID- 27885510
TI  - Left main crossover stenting in a patient with severe thrombocytopenia due to
      aplastic anemia.
AB  - A 76-year-old man with aplastic anemia presented with recurrent acute myocardial
      infarction (AMI) with heart failure. After the initial appearance of AMI
      approximately 2 months earlier, he had received conservative
      treatment/transfusion alone because of severe thrombocytopenia and anemia
      (platelet 11 * 103/MUL, hemoglobin 6.4 g/dL). Refractory heart failure persisted
      despite repeated conservative treatment/transfusion for the second AMI, and
      therefore, we performed transradial coronary angiography and left main crossover
      stenting with a bare metal stent. His critical condition markedly improved;
      however, soon after discharge, he complicated with subdural hematoma. He has
      since been free of cardiovascular/hemorrhagic events for 7 months without
      antiplatelet/anticoagulant therapy.

PMID- 27885511
TI  - Does anticoagulation therapy prevent thrombosis in coronary stent grafts?
AB  - A polytetrafluoroethylene (PTFE)-covered stent was deployed for enlarging
      coronary aneurysms in a 73-year-old man. Optical coherence tomography (OCT) and
      coronary angioscopy performed 3 months later revealed naked stent struts and thin
      patches of red thrombi covering the PTFE membrane even under dual antiplatelet
      therapy (DAPT). After 5-month warfarin administration under DAPT, OCT and
      angioscopy showed a clear extinction of the thin patches of red thrombi on the
      PTFE membrane and stent struts, although most of the struts were still naked. The
      addition of anticoagulation therapy to DAPT may reduce thrombosis events in
      patients treated with PTFE-covered stents.

PMID- 27885512
TI  - Clinicopathological features of thyroid cancer in the elderly compared to younger
      counterparts: single-center experience.
AB  - PURPOSE: The incidence of thyroid cancer is increased in elderly patients. It
      tends to be larger and have more aggressive characteristics in these patients.
      Our aim was to compare features of thyroid carcinoma in geriatric and non
      geriatric patients. METHODS: In total, 933 patients with thyroid cancer were
      retrospectively reviewed. Thyroid functions, ultrasonography features of
      malignant nodules, cytological and histopathological findings and the rates of
      recurrence and persistence were compared in patients >=65 and <65 years old.
      RESULTS: There were 153 malignant foci in 109 (11.7%) patients >=65 and 1185
      malignant foci in 824 (88.3%) patients <65 years old. Mean nodule diameter was
      significantly higher in geriatric patients (p = 0.008). Most of the
      ultrasonographical features of malignant nodules were similar in two groups.
      Hypoechoic halo was observed in 16.4 and 28.6% of malignant nodules in geriatric
      and non-geriatric group, respectively (p = 0.034). There was no significant
      difference in cytological diagnosis. Histopathologically, tumor diameter, rates
      of microcarcinomas and incidentality were similar. Of all cancer types, 88.8% in
      geriatric and 93.9% in non-geriatric group were papillary thyroid cancer (p =
      0.028). Hurthle cell cancer constituted 3.9 and 1.1% of carcinomas in geriatric
      and non-geriatric patients, respectively (p = 0.015); 2.0 and 0.2% of tumors in
      geriatric and non-geriatric group were anaplastic, respectively (p = 0.012).
      Capsular and vascular invasion, extrathyroidal extension, persistence and
      recurrence rates were similar. CONCLUSIONS: Rates of anaplastic cancer and
      Hurthle cell cancer which is known to have worser prognosis among other
      differentiated thyroid cancers are increased in geriatric ages. Cytological
      evaluation of thyroid nodules should strongly be considered due to increased
      tendency for aggressive tumor types in these patients.

PMID- 27885513
TI  - The comparison of the quality of life and intranasal edema between the patients
      with or without nasal packing after septoplasty.
AB  - Septoplasty is one of the most common operations performed in otolaryngology and
      anterior nasal packing is done routinely to prevent postoperative bleeding,
      septal hematoma or nasal synechia. Currently, transseptal sutures have gained a
      broader application area, not only for preventing the complications such as
      septal hematoma and bleeding but also closing any accidental tears of septal
      mucosa and providing additional support for the cartilage pieces retained in
      septoplasty. We evaluated the quality of life of the patients in early
      postoperative period (in the first postoperative week), intranasal edema with
      endoscopic examination and the intranasal changes with acoustic rhinometry. We
      performed a prospective and randomized study with patients undergoing septoplasty
      without inferior turbinectomy. As packing material, there were two groups: in
      group A, gauze in a glove finger and in group B, Doyle splint were used, and in
      the additional group C, only transseptal suture with 4/0 vicryl among the
      cartilaginous septum was performed. The patients were invited to control
      examinations on the postoperative 2nd, 4th and 7th days to evaluate the scores
      from 1 to 5 on the questionnaire for the pain, nasal fullness, sneezing,
      epiphora, difficulty in swallowing and sleep disturbances. The patients were also
      administered an endoscopic nasal examination for the purpose of detecting the
      intranasal edema, and acoustic rhinometry was performed during the control
      examinations to detect the intranasal changes. Total occluding packing was found
      to cause much more frequent and higher scores of epiphora, sneezing, difficulty
      in swallowing, but mainly, the pain compared to in silicone packing with airway
      and transseptal suture only. Although the silicone packing with airway was found
      to be much more comfortable, it also led to sneezing and epiphora. The patients
      without nasal packing had more comfortable period especially in the early
      postoperative days (the first 4 days). However, 1 week after surgery, groups with
      and without nasal packing were found to be equalized on behalf of the objective
      and subjective parameters. As any complication was not observed due to not using
      nasal packing, it is thought that nasal packing usage following septoplasty is
      not a necessity.

PMID- 27885514
TI  - Speech evoked auditory brainstem response and gap detection threshold in middle
      aged individual.
AB  - This study aimed at characterizing the gap detection threshold (GDT) and speech
      evoked ABR (SABR) in younger and middle-aged individuals. Two groups of subjects
      were participated in the study which includes 15 young adults in the age range of
      15-25 years and 15 middle-aged individuals in the age range of 40-60 years. SABR
      with stimulus/da/of 40 ms and GDT were investigated on both groups. For SABR,
      Mann-Whitney U test revealed that ageing has significantly adverse effect on the
      encoding of F1 and F2 at brainstem level. However, no significant effect of
      ageing (till middle age) on the encoding of F0 was observed in present study.
      Mann-Whitney U test also showed significant longer latency of wave V in middle
      aged individuals compared to younger adults. Furthermore, GDT was significantly
      better in younger adults compared to middle-aged individuals according to Mann
      Whitney U test. This study also revealed no significant correlation between GDT
      and F0, F1, F2 for younger as well as middle-aged individuals. The findings of
      this study showed poor encoding of certain aspects of speech at brainstem level
      in middle-aged individuals compared to younger adults. This study also revealed
      deterioration of auditory processes in middle-aged individuals.

PMID- 27885516
TI  - Development of a high-pressure set-up for measurements of binary diffusion
      coefficients in supercritical carbon dioxide.
AB  - We present the development of a high-pressure apparatus for measurements of
      diffusion coefficients in supercritical fluids. The Taylor dispersion method has
      been adapted to conduct experiments at the pressures up to 25.0 MPa. In order to
      test the developed set-up, binary diffusion coefficients D at infinite dilution
      in supercritical carbon dioxide have been measured for a reference system,
      benzene, at temperatures in the range of 309.50-319.95 K. The effects of flow
      velocity, number of consecutive injections and absorbance at different wave
      numbers on the diffusion coefficient have been analysed. The obtained diffusion
      coefficients are of the order of 10-8 m 2/s and in excellent agreement with the
      available literature data.

PMID- 27885515
TI  - Biological mesh extrusion months after laparoscopic ventral rectopexy.

PMID- 27885517
TI  - Octupolar order in three dimensions.
AB  - Octupolar order in three space dimensions is described by a real-valued, fully
      symmetric and traceless, third-rank tensor A. The real generalized eigenvalues of
      A are also the critical values of a real-valued potential [Formula: see text]
      defined on the unit sphere [Formula: see text] by A. Generalized eigenvalues of A
      and critical points of [Formula: see text] are equivalent means to describe
      octupolar order in a molecular assembly according to Buckingham's formula for the
      probability density distribution. Intuition suggests that [Formula: see text]
      would generically have four maxima, corresponding to the most probable molecular
      orientations, so that a (possibly distorted) tetrahedron would effectively
      describe A. This paper shows that another generic octupolar state flanks the
      expected one, featuring three maxima of [Formula: see text]. The two generic
      states are divided by a separatrix manifold, which may physically represent an
      intra-octupolar transition.

PMID- 27885518
TI  - Does ozone clinically enhance the remineralizing potential of nano-hydroxyapatite
      on initial enamel lesions?

PMID- 27885519
TI  - Domestic horses send signals to humans when they face with an unsolvable task.
AB  - Some domestic animals are thought to be skilled at social communication with
      humans due to the process of domestication. Horses, being in close relationship
      with humans, similar to dogs, might be skilled at communication with humans.
      Previous studies have indicated that they are sensitive to bodily signals and the
      attentional state of humans; however, there are few studies that investigate
      communication with humans and responses to the knowledge state of humans. Our
      first question was whether and how horses send signals to their potentially
      helpful but ignorant caretakers in a problem-solving situation where a food item
      was hidden in a bucket that was accessible only to the caretakers. We then
      examined whether horses alter their behaviours on the basis of the caretakers'
      knowledge of where the food was hidden. We found that horses communicated to
      their caretakers using visual and tactile signals. The signalling behaviour of
      the horses significantly increased in conditions where the caretakers had not
      seen the hiding of the food. These results suggest that horses alter their
      communicative behaviour towards humans in accordance with humans' knowledge
      state.

PMID- 27885520
TI  - The effect of pre-operative topical anaesthetic cream on the ablative width and
      coagulative depth of ablative fractional resurfacing laser.
AB  - Topical anaesthetic cream (TAC) is commonly used as a pre-treatment of ablative
      fractional resurfacing (AFR) laser. Most of anaesthetic cream contains distilled
      water as major component. Therefore, pre-operative TAC may interfere the
      photothermal reaction in the skin treated with fractional carbon-dioxide (FCO2)
      laser and fractional erbium-doped yttrium aluminium garnet (FEr:YAG) laser. The
      objective of the study was to compare the ablative width (AW) and coagulative
      depth (CD) of AFR laser with and without pre-treatment with TAC. Four Thai
      females who underwent abdominoplasty were included in the study. The excised skin
      of each subject was divided into four areas. TAC (eutectic mixture of local
      anaesthesia; EMLA) with 1-h occlusion was applied only on the first and second
      areas. The first and third areas were treated with FCO2 at 15 mj and 5% density.
      The second and fourth areas were treated with FEr:YAG at 28 J/cm2 and 5% density.
      Six biopsied specimens were obtained from each area. A total of 96 specimens (24
      specimens from each area) were collected from four patients and examined randomly
      by two dermatopathologists. The ablative width and coagulative depth from each
      specimen were determined. In FCO2-treated specimens, the mean AW of the specimens
      that were pre-treated with TAC and control was 174.86 +/- 24.57 and 188.52 +/-
      41.32 MUm. The mean CD of the specimens that were pre-treated with TAC and
      control was 594.96 +/- 111.72 and 520.03 +/- 147.40 MUm. There were no
      significant differences in AW and CD between both groups (p = 0.53 and p = 0.15).
      In FEr:YAG-treated specimens, the mean AW of the specimens that were pre-treated
      with TAC and control was 381.11 +/- 48.02 and 423.65 +/- 60.16 MUm. The mean CD
      of the specimens that were pre-treated with TAC and control was 86.03 +/- 29.44
      and 71.59 +/- 18.99 MUm. There were no significant differences in AW and CD
      between both groups (p = 0.16 and p = 0.24). The pre-treatment with TAC provided
      no statistically difference from the control group on AW and CD of both FCO2 and
      FEr:YAG laser irradiation. However, there was a tendency to have narrower AW and
      deeper CD of the areas that were pre-treated with TAC when comparing to that of
      the control.

PMID- 27885521
TI  - Laser and LED phototherapy on midpalatal suture after rapid maxilla expansion:
      Raman and histological analysis.
AB  - The aim of this study was to analyze the effect of laser or LED phototherapy on
      the acceleration of bone formation at the midpalatal suture after rapid maxilla
      expansion. Forty-five rats were divided into groups at 7 days (control,
      expansion, expansion and laser irradiation, and expansion and LED irradiation)
      and into 14 days (expansion, expansion and laser in the 1st week, expansion and
      LED in the 1st week, expansion and laser in the 1st and 2nd weeks, expansion and
      LED in the 1st and 2nd weeks). Laser/LED irradiation occurred every 48 h.
      Expansion was accomplished with a spatula and maintained with a triple helicoid
      of 0.020-in stainless steel orthodontic wire. A diode laser (lambda780 nm, 70 mW,
      spot of 0.04 cm2, t = 257 s, SAEF of 18 J/cm2) or a LED (lambda850 +/- 10 nm, 150
      +/- 10 mW, spot of 0.5 cm2, t = 120 s, SAEF of 18 J/cm2) was applied in one point
      in the midpalatal suture immediately behind the upper incisors. Raman
      spectroscopy and histological analyses of the suture region were carried and data
      was submitted to statistical analyses (p <= 0.05). Raman spectrum analysis
      demonstrated that irradiation increases hydroxyapatite in the midpalatal suture
      after expansion. In the histological analysis of various inflammation, there was
      a higher production of collagen and osteoblastic activity and less osteoclastic
      activity. The results showed that LED irradiation associated to rapid maxillary
      expansion improves bone repair and could be an alternative to the use of laser in
      accelerating bone formation in the midpalatal suture.

PMID- 27885522
TI  - Efficacy and safety of fractional CO2 laser versus fractional Er:YAG laser in the
      treatment of facial skin wrinkles.
AB  - Ablative fractional lasers were introduced for treating facial rhytides. Few
      studies have compared fractional CO2 and Er:YAG lasers on cutaneous photodamages
      by a split trial. The aim of the present study was to compare these modalities in
      a randomized controlled double-blind split-face design with multiple sessions and
      larger sample size compared to previous studies done before. Forty patients with
      facial wrinkles were enrolled. Patients were randomly assigned to receive three
      monthly treatments on each side of the face, one with a fractional CO2 and one
      with a fractional Er:YAG laser. The evaluations included investigating clinical
      outcome determined by two independent dermatologists not enrolled in the
      treatment along with measuring skin biomechanical property of cheeks using a
      sensitive biometrologic device with the assessment of cutaneous resonance running
      time (CRRT). Moreover, possible side effects and patients' satisfaction have been
      recorded at baseline, 1 month after each treatment, and 3 months after the last
      treatment session. Clinical assessment showed both modalities significantly
      reduce facial wrinkles (p value < 0.05), with no appreciable difference between
      two lasers. Mean CRRT values also decreased significantly after the laser
      treatment compared to the baseline in both laser groups. There was no serious
      long-standing adverse effect after both laser treatments, but the discomfort was
      more pronounced by the participants after CO2 laser treatment. According to the
      present study, both fractional CO2 and fractional Er:YAG lasers show considerable
      clinical improvement of facial skin wrinkles with no serious adverse effects, but
      post-treatment discomfort seems to be lower with Er:YAG laser.

PMID- 27885523
TI  - A review of the mechanism of action of lasers and photodynamic therapy for
      onychomycosis.
AB  - Onychomycosis is one of the most common diseases in the field of dermatology. It
      refers to the fungal infection of the nail plate or nail bed with high incidence
      in the general population. The available treatment options for onychomycosis have
      limited use due to side effects, drug interactions, and contraindications, which
      necessitates the application of an alternative treatment for onychomycosis. In
      the recent years, lasers and photodynamic therapy (PDT) have been recognized as
      alternative treatment options. Most of the previous studies have found them to be
      safe and effective treatment modalities in this indication; however, the results
      varied greatly and the in vitro and in vivo outcomes are contradictory. In the
      present review, studies related to the mechanism of action of lasers and PDT for
      the treatment of onychomycosis will be discussed, with a focus on to find
      explanation to the contradictory results.

PMID- 27885524
TI  - cAMP-Dependent Protein Kinase and cGMP-Dependent Protein Kinase as Cyclic
      Nucleotide Effectors.
AB  - The cAMP-dependent protein kinase (PKA) and the cGMP-dependent protein kinase
      (PKG) are homologous enzymes with different binding and activation specificities
      for cyclic nucleotides. Both enzymes harbor conserved cyclic nucleotide-binding
      (CNB) domains. Differences in amino acid composition of these CNB domains mediate
      cyclic nucleotide selectivity in PKA and PKG, respectively. Recently, the
      presence of the noncanonical cyclic nucleotides cCMP and cUMP in eukaryotic cells
      has been proven, while the existence of cellular cIMP and cXMP remains unclear.
      It was shown that the main effectors of cyclic nucleotide signaling, PKA and PKG,
      can be activated by each of these noncanonical cyclic nucleotides. With unique
      effector proteins still missing, such cross-activation effects might have
      physiological relevance. Therefore, we approach PKA and PKG as cyclic nucleotide
      effectors in this chapter. The focus of this chapter is the general cyclic
      nucleotide-binding properties of both kinases as well as the selectivity for cAMP
      or cGMP, respectively. Furthermore, we discuss the binding affinities and
      activation potencies of noncanonical cyclic nucleotides.

PMID- 27885525
TI  - Histamine H1 Receptor Gene Expression and Drug Action of Antihistamines.
AB  - The upregulation mechanism of histamine H1 receptor through the activation of
      protein kinase C-delta (PKCdelta) and the receptor gene expression was
      discovered. Levels of histamine H1 receptor mRNA and IL-4 mRNA in nasal mucosa
      were elevated by the provocation of nasal hypersensitivity model rats.
      Pretreatment with antihistamines suppressed the elevation of mRNA levels. Scores
      of nasal symptoms were correlatively alleviated to the suppression level of mRNAs
      above. A correlation between scores of nasal symptoms and levels of histamine H1
      receptor mRNA in the nasal mucosa was observed in patients with pollinosis. Both
      scores of nasal symptoms and the level of histamine H1 receptor mRNA were
      improved by prophylactic treatment of antihistamines. Similar to the
      antihistamines, pretreatment with antiallergic natural medicines showed
      alleviation of nasal symptoms with correlative suppression of gene expression in
      nasal hypersensitivity model rats through the suppression of PKCdelta. Similar
      effects of antihistamines and antiallergic natural medicines support that
      histamine H1 receptor-mediated activation of histamine H1 receptor gene
      expression is an important signaling pathway for the symptoms of allergic
      diseases. Antihistamines with inverse agonist activity showed the suppression of
      constitutive histamine H1 receptor gene expression, suggesting the advantage of
      therapeutic effect.

PMID- 27885526
TI  - Twelve-year follow-up of penetrating keratoplasty.
AB  - PURPOSE: To evaluate the long-term outcomes of penetrating keratoplasty (PKP)
      according to the corneal disease diagnosis and the number of PKP procedures
      performed. METHODS: Five-hundred-and-nine eyes from 403 patients who underwent
      PKP at Miyata Eye Hospital in Japan from 1998 through 2014, were included in this
      study. Medical charts were retrospectively examined to ascertain the corneal
      disease diagnosis and the period of graft survival. Graft survival rates were
      compared among various corneal disease diagnoses and among the number of PKP
      procedures performed. Changes in corneal endothelial cell density (ECD) were
      analyzed using a mixed-effects model. The presence/absence of various risk
      factors was compared between transparent grafts and failed grafts. RESULTS: The
      overall rate of graft survival at 12 years was 60.4%. The rates of graft survival
      in keratoconus was 100%, in corneal dystrophy 100%, in leukoma 70.8%, and in
      bullous keratopathy 51.7%. The rates of graft survival at 12 years for the first
      PKP was 65.4% and for the second PKP, 43.4% (p < 0.001). All cases of third PKP
      and fourth PKP failed within 8 years. Preoperative mean ECD (95% confidence
      interval) was 2722 (2666-2778) cells/mm2; it decreased exponentially after PKP.
      Mean ECD was 659 (440-878) cells/mm2 at 10 years. Rejection, trauma, and
      infection occurred significantly more frequently in failed grafts than in
      transparent grafts. CONCLUSIONS: The long-term prognosis of PKP depends on the
      original diagnosis. The long-term prognosis of re-grafting is worse than that of
      primary grafts. Rejection, trauma, and infection are risk factors for graft
      failure.

PMID- 27885528
TI  - A network biology approach to understanding the importance of chameleon proteins
      in human physiology and pathology.
AB  - Chameleon proteins are proteins which include sequences that can adopt alpha
      helix-beta-strand (HE-chameleon) or alpha-helix-coil (HC-chameleon) or beta
      strand-coil (CE-chameleon) structures to operate their crucial biological
      functions. In this study, using a network-based approach, we examined the
      chameleon proteins to give a better knowledge on these proteins. We focused on
      proteins with identical chameleon sequences with more than or equal to seven
      residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon,
      and CE-chameleon structures in the same protein. One hundred and ninety-one human
      chameleon proteins were identified via our in-house program. Then, protein
      protein interaction (PPI) networks, Gene ontology (GO) enrichment, disease
      network, and pathway enrichment analyses were performed for our derived data set.
      We discovered that there are chameleon sequences which reside in protein-protein
      interaction regions between two proteins critical for their dual function.
      Analysis of the PPI networks for chameleon proteins introduced five hub proteins,
      namely TP53, EGFR, HSP90AA1, PPARA, and HIF1A, which were presented in four PPI
      clusters. The outcomes demonstrate that the chameleon regions are in critical
      domains of these proteins and are important in the development and treatment of
      human cancers. The present report is the first network-based functional study of
      chameleon proteins using computational approaches and might provide a new
      perspective for understanding the mechanisms of diseases helping us in developing
      new medical therapies along with discovering new proteins with chameleon
      properties which are highly important in cancer.

PMID- 27885527
TI  - Insights into mortality patterns and causes of death through a process point of
      view model.
AB  - Process point of view (POV) models of mortality, such as the Strehler-Mildvan and
      stochastic vitality models, represent death in terms of the loss of survival
      capacity through challenges and dissipation. Drawing on hallmarks of aging, we
      link these concepts to candidate biological mechanisms through a framework that
      defines death as challenges to vitality where distal factors defined the age
      evolution of vitality and proximal factors define the probability distribution of
      challenges. To illustrate the process POV, we hypothesize that the immune system
      is a mortality nexus, characterized by two vitality streams: increasing vitality
      representing immune system development and immunosenescence representing vitality
      dissipation. Proximal challenges define three mortality partitions: juvenile and
      adult extrinsic mortalities and intrinsic adult mortality. Model parameters,
      generated from Swedish mortality data (1751-2010), exhibit biologically
      meaningful correspondences to economic, health and cause-of-death patterns. The
      model characterizes the twentieth century epidemiological transition mainly as a
      reduction in extrinsic mortality resulting from a shift from high magnitude
      disease challenges on individuals at all vitality levels to low magnitude stress
      challenges on low vitality individuals. Of secondary importance, intrinsic
      mortality was described by a gradual reduction in the rate of loss of vitality
      presumably resulting from reduction in the rate of immunosenescence. Extensions
      and limitations of a distal/proximal framework for characterizing more explicit
      causes of death, e.g. the young adult mortality hump or cancer in old age are
      discussed.

PMID- 27885530
TI  - Protein Secretion in Gram-Positive Bacteria: From Multiple Pathways to
      Biotechnology.
AB  - A number of Gram-positive bacteria are important players in industry as producers
      of a diverse array of economically interesting metabolites and proteins. As
      discussed in this overview, several Gram-positive bacteria are valuable hosts for
      the production of heterologous proteins. In contrast to Gram-negative bacteria,
      proteins secreted by Gram-positive bacteria are released into the culture medium
      where conditions for correct folding are more appropriate, thus facilitating the
      isolation and purification of active proteins. Although seven different protein
      secretion pathways have been identified in Gram-positive bacteria, the majority
      of heterologous proteins are produced via the general secretion or Sec pathway.
      Not all proteins are equally well secreted, because heterologous protein
      production often faces bottlenecks including hampered secretion, susceptibility
      to proteases, secretion stress, and metabolic burden. These bottlenecks are
      associated with reduced yields leading to non-marketable products. In this
      chapter, besides a general overview of the different protein secretion pathways,
      possible hurdles that may hinder efficient protein secretion are described and
      attempts to improve yield are discussed including modification of components of
      the Sec pathway. Attention is also paid to omics-based approaches that may offer
      a more rational approach to optimize production of heterologous proteins.

PMID- 27885529
TI  - Lack of Aquaporin 9 Reduces Brain Angiogenesis and Exaggerates Neuronal Loss in
      the Hippocampus Following Intracranial Hemorrhage in Mice.
AB  - Intracranial hemorrhage (ICH) is a common subtype of stroke with high morbidity
      and mortality. However, few clinical therapies that can reduce ICH-induced brain
      injury and promote the recovery outcome in ICH patients are available to improve
      the recovery from ICH. Given that aquaporin 9 (AQP9) plays a critical role in
      brain edema after ischemic stroke and traumatic brain injury and is involved in
      the regulation of angiogenesis, we examined the role of AQP9 in preventing
      neuronal loss and in neovascularization in the dorsal hippocampus (DH) after ICH.
      We found that intra-DH collagenase-induced ICH increased AQP9 protein levels in
      the hippocampus, which was associated with behavioral deficits in wild-type mice.
      However, ICH robustly enhanced behavioral deficits in the AQP9-null mice, as
      compared with the wild-type mice. Furthermore, neovascularization and
      proliferation of brain microvascular endothelial cells following ICH were
      severely impaired in the AQP9-null mice, as compared with the wild-type mice.
      Finally, hippocampal neuronal loss following ICH became severer in the AQP9-null
      mice, relative to the wild-type mice. Taken together, our findings indicated that
      AQP9 in the brain may play a compensatory role in response to ICH, promote brain
      angiogenesis, and prevent subsequent neuronal death, thus preventing the
      deterioration of neurological outcome of ICH.

PMID- 27885531
TI  - Evolution of Liver Steatosis Quantified by MR Imaging and MR Spectroscopy, in
      Morbidly Obese Patients Undergoing Sleeve Gastrectomy: Short-Term Outcomes.
AB  - BACKGROUND: Currently, the standard procedure used to evaluate hepatic steatosis
      is the liver biopsy. This is an invasive practice that presents inherent risks.
      Increasing evidence suggests that magnetic resonance imaging (MRI) and MR
      spectroscopy (MRS) may represent an accurate method to determine the hepatic
      lipid content. The aim of this study was to evaluate the effect of sleeve
      gastrectomy on liver steatosis, quantified by MRI and MRS. PATIENTS AND METHODS:
      A prospective observational study of patients undergoing laparoscopic sleeve
      gastrectomy was performed. All patients underwent a MRI and a MRS study 2 weeks
      before the intervention and 6 months after the surgery. Anthropometric,
      biochemical, and radiological parameters were analyzed. RESULTS: Twenty-three
      patients were included, 21 females and 2 males, with a mean age of 47.6 +/- 10.6
      years and mean pre-op BMI 47.6 +/- 6.7 Kg/m2. Six months after surgery, mean BMI
      was 32.2 +/- 5.1 Kg/m2, with a mean excess weight loss of 68.2 +/- 18.6%. Mean
      preoperative hepatic volume was 1999.9 +/- 436.2 ml and 6 months after surgery it
      decreased to 1568 +/- 170.3 ml (p = 0.005). Mean preoperative percentage of lipid
      content was 14.2 +/- 15.4% and 6 months after surgery, it decreased to 4.3 +/-
      3.2% (p = 0.007). A significant reduction of steatosis grade was observed, with
      disappearance of preoperative steatosis in 54.9% of the patients. CONCLUSION: Six
      months after sleeve gastrectomy, a significant reduction of liver steatosis is
      observed, as demonstrated by reduction in the percentage of intrahepatocitary
      lipids and liver volume, determined by MRS and MRI. These imaging techniques can
      be considered as noninvasive, accurate methods for monitoring liver steatosis in
      morbidly obese patients undergoing bariatric surgery.

PMID- 27885533
TI  - The Yield and Validity of Preoperative Gastroscopy in Bariatric Surgery.

PMID- 27885532
TI  - Whey Protein Supplementation Enhances Body Fat and Weight Loss in Women Long
      After Bariatric Surgery: a Randomized Controlled Trial.
AB  - BACKGROUND: The ideal nutritional approach for weight regain after bariatric
      surgery remains unclear. OBJECTIVE: The objective of this study is to assess the
      effect of whey protein supplementation on weight loss and body composition of
      women who regained weight 24 or more months after bariatric surgery. METHODS:
      This is a 16-week open-label, parallel-group, randomized controlled trial of
      women who regained at least 5 % of their lowest postoperative weight after a Roux
      en-Y gastric bypass (RYGB). A total of 34 participants were treated with
      hypocaloric diet and randomized (1:1) to receive or not supplementation with whey
      protein, 0.5 g/kg of the ideal body weight. The primary outcomes were changes in
      body weight, fat free mass (FFM), and fat mass (FM), evaluated by tetrapolar
      bioelectrical impedance analysis (BIA). Secondary outcomes included resting
      energy expenditure, blood glucose, lipids, adiponectin, interleukin 6 (IL-6), and
      cholecystokinin levels. Statistical analyses included generalized estimating
      equations adjusted for age and physical activity. RESULTS: Fifteen patients in
      each group were evaluated: mean age was 45 +/- 11 years, body mass index (BMI)
      was 35.7 +/- 5.2 kg/m2, and time since surgery was 69 +/- 23 months. Protein
      intake during follow-up increased by approximately 75 % in the intervention group
      (p = 0.01). The intervention group presented more body weight loss (1.86 kg, p =
      0.017), accounted for FM loss (2.78, p = 0.021) and no change in FFM, as compared
      to controls (gain of 0.42 kg of body weight and 0.6 kg of FM). No differences in
      secondary outcomes were observed between groups. CONCLUSIONS: Whey protein
      supplementation promoted body weight and FM loss in women with long-term weight
      regain following RYGB.

PMID- 27885534
TI  - Zinc Deficiency after Gastric Bypass for Morbid Obesity: a Systematic Review.
AB  - Up to 50% of patients have zinc deficiency before bariatric surgery. Roux-en-Y
      gastric bypass (RYGB) is the commonest bariatric procedure worldwide. It can
      further exacerbate zinc deficiency by reducing intake as well as absorption. The
      British Obesity and Metabolic Surgery Society, therefore, recommends that zinc
      level should be monitored routinely following gastric bypass. However, the
      American guidance does not recommend such monitoring for all RYGB patients and
      reserves it for patients with 'specific findings'. This review concludes that
      clinically relevant Zn deficiency is rare after RYGB. Routine monitoring of zinc
      levels is hence unnecessary for asymptomatic patients after RYGB and should be
      reserved for patients with skin lesions, hair loss, pica, dysgeusia, hypogonadism
      or erectile dysfunction in male patients, and unexplained iron deficiency
      anaemia.

PMID- 27885535
TI  - Preserved Fat-Free Mass after Gastric Bypass and Duodenal Switch.
AB  - BACKGROUND: Concerns for the possibility of an excessive loss of fat-free mass
      (FFM) and resting metabolic rate (RMR) after bariatric surgery, such as Roux-en-Y
      gastric bypass (RYGB) and duodenal switch (BPD/DS), have been raised. OBJECTIVES:
      This study aims to examine body composition and RMR in patients after RYGB and
      BPD/DS and in non-operated controls. METHODS: Body composition and RMR were
      studied with Bod Pod and indirect calorimetry in weight-stable RYGB (n = 15) and
      BPD/DS patients (n = 12) and compared with non-operated controls (n = 17). All
      patients were 30-55 years old and weight stable with BMI 28-35 kg/m2. RESULTS:
      FFM% was 58% (RYGB), 61% (BPD/DS), and 58% (controls). Body composition did not
      differ after RYGB and BPD/DS compared to controls, despite 27 and 40% total body
      weight loss, respectively. No difference in RMR or RMR/FFM was observed (1539,
      1617, and 1490 kcal/24 h; and 28.9, 28.4, and 28.8 kcal/24 h/kg). CONCLUSION:
      Weight-stable patients with BMI 28-35 kg/m2 after RYGB and BPD/DS have a body
      composition and RMR similar to that of non-operated individuals within the same
      BMI interval.

PMID- 27885537
TI  - Safety Analysis of Bariatric Patients Undergoing Outpatient Upper Endoscopy with
      Non-Anesthesia Administered Propofol Sedation.
AB  - BACKGROUND: Non-anesthesia administered propofol (NAAP) has been shown to be a
      safe and effective method of sedation for patients undergoing gastrointestinal
      endoscopy. Bariatric surgery patients are potentially at a higher risk for
      sedation-related complications due to co-morbidities including obstructive sleep
      apnea. The outcomes of NAAP in bariatric patients have not been previously
      reported. METHODS: In this retrospective cohort study, severely obese patients
      undergoing pre-surgical outpatient esophagogastroduodenoscopy (EGD) were compared
      to non-obese control patients (BMI <= 25 kg/m2) undergoing diagnostic EGD at our
      institution from March 2011-September 2015 using our endoscopy database.
      Patients' demographics and procedural and recovery data, including any airway
      interventions, were statistically analyzed. RESULTS: We included 130 consecutive
      pre-operative bariatric surgical patients with average BMI 45.8 kg/m2 (range 34
      80) and 265 control patients with average BMI 21.9 kg/m2 (range 14-25). The
      severely obese group had a higher prevalence of sleep apnea (62 vs 8%; p <
      0.001), experienced more oxygen desaturations (22 vs 7%; p < 0.001), and received
      more chin lift maneuvers (20 vs 6%; p < 0.001). Advanced airway interventions
      were rarely required in either group and were not more frequent in the bariatric
      group. CONCLUSIONS: With appropriate training of endoscopy personnel, NAAP is a
      safe method of sedation in severely obese patients undergoing outpatient upper
      endoscopy.

PMID- 27885536
TI  - Safety and Outcome of Laparoscopic Sleeve Gastrectomy Following Removal of
      Adjustable Gastric Banding: Lessons from 109 Patients in a Single Center and
      Review of the Literature.
AB  - BACKGROUND: Although considered a common bariatric procedure, laparoscopic
      adjustable gastric banding (LAGB) is associated with high rates of weight loss
      failure and long-term complications. PURPOSE: The purpose of this study was to re
      assess the safety and outcome of conversion of failed LAGB to laparoscopic sleeve
      gastrectomy (LSG). MATERIALS AND METHODS: One hundred and nine patients underwent
      conversion from LAGB to LSG (78 females, mean age 43 +/- 11.3 years, mean BMI
      42.4 +/- 7.4 kg/m2). Patient demographics, obesity-related co-morbidities, BMI
      before and after the procedure, post-operative complications, and length of
      hospital stay were documented. RESULTS: All cases were completed laproscopically,
      with 88% (n = 96) performed in a single stage. Fourteen patients developed early
      post-operative complications (12.8%), including two leaks and three post
      operative bleeding. There were no mortalities in this series. Average BMI at
      least 1-year following surgery was 33 +/- 5.3 kg/m2 (excess weight loss (EWL) =
      53.7%). CONCLUSIONS: Our data suggests that conversion of failed LAGB to LSG is
      both safe and effective. Randomized controlled studies comparing conversion of a
      failed LAGB to sleeve gastrectomy versus other bariatric operations are necessary
      to clarify the optimal conversion procedure.

PMID- 27885539
TI  - "PQRST": the shamrock method for lumbar plexus blocks.

PMID- 27885538
TI  - Multi-institutional prospective feasibility study to explore tolerability and
      efficacy of oral nutritional supplements for patients with gastric cancer
      undergoing gastrectomy (CCOG1301).
AB  - BACKGROUND: Postoperative malnutrition after gastrectomy is deemed inevitable,
      which could have prejudicial influence on survival for gastric cancer patients. A
      prospective feasibility study was conducted to evaluate the efficacy of
      postoperative oral nutritional supplements. METHODS: Stage I-III gastric cancer
      patients who underwent distal or total gastrectomy received oral administration
      of Racol(r) NF (Otsuka Pharmaceutical Factory, Japan), a liquid enteral
      nutritional formula, as a supplement to regular meals. Racol(r) NF administration
      at a recommended dosage of 400 kcal/400 ml per day was started within 7 days
      postoperatively and was continued for 3 months postoperatively. The primary end
      point was ratio of the weight loss at 3 months postoperatively to the
      preoperative body weight (body weight loss ratio). Secondary end points were the
      adherence to Racol(r) NF therapy and changes in body composition. RESULTS: One
      hundred eighteen patients were registered before surgery, 82 of whom were
      eligible for efficacy analyses. The average rate of body weight loss after 3
      months postoperatively was 8.3%. The mean daily intake of Racol(r) NF was 211 ml.
      There was a significant correlation between adherence to Racol(r) NF therapy and
      body weight loss ratio (P < 0.001). Adherence to Racol(r) NF therapy was the only
      factor that correlated with the body weight loss ratio among all clinical
      characteristics by the multiple linear regression analysis (P = 0.007).
      CONCLUSIONS: Oral nutritional supplementation with Racol(r) NF led to a
      significant reduction in body weight loss for gastrectomized patients who
      tolerated more than 200 ml of the nutrient per day compared with those who could
      not tolerate this amount.

PMID- 27885541
TI  - Erratum to: Workplace Outcomes in Work-Disability Prevention Research: A Review
      with Recommendations for Future Research.

PMID- 27885540
TI  - Automatic abdominal multi-organ segmentation using deep convolutional neural
      network and time-implicit level sets.
AB  - PURPOSE: Multi-organ segmentation from CT images is an essential step for
      computer-aided diagnosis and surgery planning. However, manual delineation of the
      organs by radiologists is tedious, time-consuming and poorly reproducible.
      Therefore, we propose a fully automatic method for the segmentation of multiple
      organs from three-dimensional abdominal CT images. METHODS: The proposed method
      employs deep fully convolutional neural networks (CNNs) for organ detection and
      segmentation, which is further refined by a time-implicit multi-phase evolution
      method. Firstly, a 3D CNN is trained to automatically localize and delineate the
      organs of interest with a probability prediction map. The learned probability map
      provides both subject-specific spatial priors and initialization for subsequent
      fine segmentation. Then, for the refinement of the multi-organ segmentation,
      image intensity models, probability priors as well as a disjoint region
      constraint are incorporated into an unified energy functional. Finally, a novel
      time-implicit multi-phase level-set algorithm is utilized to efficiently optimize
      the proposed energy functional model. RESULTS: Our method has been evaluated on
      140 abdominal CT scans for the segmentation of four organs (liver, spleen and
      both kidneys). With respect to the ground truth, average Dice overlap ratios for
      the liver, spleen and both kidneys are 96.0, 94.2 and 95.4%, respectively, and
      average symmetric surface distance is less than 1.3 mm for all the segmented
      organs. The computation time for a CT volume is 125 s in average. The achieved
      accuracy compares well to state-of-the-art methods with much higher efficiency.
      CONCLUSION: A fully automatic method for multi-organ segmentation from abdominal
      CT images was developed and evaluated. The results demonstrated its potential in
      clinical usage with high effectiveness, robustness and efficiency.

PMID- 27885543
TI  - Realism and Impartiality: Making Sustainability Effective in Decision-Making.
AB  - There is both individual and collective widespread concern in society about the
      impact of human activity and the effects of our decisions on the physical and
      social environment. This concern is included within the idea of sustainability.
      The meaning of the concept is still ambiguous and its practical effectiveness
      disputed. Like many other authors, this article uses as a starting point the
      definition proposed by the World Commission on Environment and Development (Our
      common future, Oxford University Press, Oxford, 1987), considering it to be a
      proposal for changing the assessment of the effects of decisions, from at least
      two perspectives: (1) what effects we should consider and (2) how we should
      assess them. Based on this double perspective, sustainability is explored as a
      method for decision-making which both expands the assessment of the consequences,
      and also provides an objective criterion for such assessment. It will be argued
      that the idea of sustainability, seen from this perspective, brings to decision
      making two qualities which had been partially lost: realism and impartiality. In
      turn, the criteria for realism and impartiality in decision-making can be used to
      identify the limitations of some partial approaches to sustainability, which
      suffer from insufficient realism (emotional altruism), insufficient impartiality
      (tactical altruism) or both phenomena at once (egoism). The article concludes by
      demonstrating how realism and impartiality provide the basis for a new form of
      sustainable decision-making (ethical sustainability), which is dependent on the
      development of two moral virtues, prudence and benevolence, and which brings
      practical effectiveness and ethical sense to the concept of sustainability.

PMID- 27885544
TI  - Do You Ignore Information Security in Your Journal Website?
AB  - Nowadays, web-based applications extend to all businesses due to their advantages
      and easy usability. The most important issue in web-based applications is
      security. Due to their advantages, most academic journals are now using these
      applications, with papers being submitted and published through their websites.
      As these websites are resources for knowledge, information security is primary
      for maintaining their integrity. In this opinion piece, we point out
      vulnerabilities in certain websites and introduce the potential for future
      threats. We intend to present how some journals are vulnerable and what will
      happen if a journal can be infected by attackers. This opinion is not a technical
      manual in information security, it is a short inspection that we did to improve
      the security of academic journals.

PMID- 27885542
TI  - A consensus statement on the gender perspective in lung cancer.
AB  - Lung cancer is the most common cancer globally and has the highest mortality.
      Although this disease is not associated with a particular gender, its incidence
      is rising among women, who are diagnosed at an increasingly younger age compared
      with men. One of the main reasons for this rise is women taking up smoking.
      However, many non-smoking women also develop this disease. Other risk factors
      implicated in the differential development of lung cancer in women are genetic
      predisposition, tumour histology and molecular profile. Proportionally more women
      than men with lung cancer have a mutation in the EGFR gene. This consensus
      statement reviews the available evidence about the epidemiological, biological,
      diagnostic, therapeutic, social and psychological aspects of lung cancer in
      women.

PMID- 27885545
TI  - Optimization of scan initiation timing after 11C-methionine administration for
      the diagnosis of suspected recurrent brain tumors.
AB  - OBJECTIVE: 11C-Methionine (MET) positron emission tomography (PET) imaging is a
      valuable technique for the evaluation of primary and recurrent brain tumors. Many
      studies have used MET-PET for data acquisition starting at 20 min after the
      tracer injection, while others have used scan initiation times at 5-15 min
      postinjection. No previous studies have identified the best acquisition timing
      during MET-PET imaging for suspected recurrent brain tumors. Here we sought to
      determine the optimal scan initiating timing after MET administration for the
      detection of recurrent brain tumors. MATERIALS AND METHODS: Twenty-three
      consecutive patients with suspected recurrent brain tumors underwent MET-PET
      examinations. Brain PET images were reconstructed from the four serial data sets
      (10-15, 15-20, 20-25, and 25-30 min postinjection) that were obtained using the
      list-mode acquisition technique. We determined the maximal standardized uptake
      values (SUVmax) of the target lesions and the target-to-normal-tissue ratios
      (TNRs), calculated as the SUVmax to the SUVmean of a region of interest placed on
      the normal contralateral frontal cortex. Target lesions without significant MET
      uptake were excluded. RESULTS: Thirty-one lesions from 23 patients were enrolled.
      There were no significant differences in MET SUVmax or TNR values among the PET
      images that were reconstructed with the data extracted from the four phases
      postinjection. CONCLUSION: The MET uptake in the suspected recurrent brain tumors
      was comparable among all data extraction time phases from 10 to 30 min
      postinjection. The scan initiation time of MET-PET at 10 min after the injection
      is allowable for the detection of recurrent brain tumors. The registration
      identification number of the original study is 1002.

PMID- 27885546
TI  - Target-specific NMR detection of protein-ligand interactions with antibody
      relayed 15N-group selective STD.
AB  - Fragment-based drug design has been successfully applied to challenging targets
      where the detection of the weak protein-ligand interactions is a key element. 1H
      saturation transfer difference (STD) NMR spectroscopy is a powerful technique for
      this work but it requires pure homogeneous proteins as targets. Monoclonal
      antibody (mAb)-relayed 15N-GS STD spectroscopy has been developed to resolve the
      problem of protein mixtures and impure proteins. A 15N-labelled target-specific
      mAb is selectively irradiated and the saturation is relayed through the target to
      the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the
      approach is experimentally feasible in a reasonable time frame. This method
      allows detection and identification of binding molecules directly from a protein
      mixture in a multicomponent system.

PMID- 27885548
TI  - Health-related quality of life in long-term survivors of acute lymphoblastic
      leukemia in childhood and adolescence.
AB  - PURPOSE: Children with acute lymphoblastic leukemia (ALL), the commonest form of
      cancer in this age group, suffer considerable morbidity during treatment, with
      the majority returning to good health soon after therapy has been completed, as
      reflected in health-related quality of life (HRQL). However, survivors are at
      risk of many adverse health outcomes later, including obesity, measured by body
      mass index (BMI), that is compounded by limited physical activity. This study
      examined the HRQL of long-term survivors of ALL and its relationship to BMI and
      physical activity. METHODS: A cohort of 75 subjects who were more than 10 years
      from diagnosis was assessed for BMI (weight in kg/height in m2) and completed two
      questionnaires. HRQL was measured by the multi-attribute, preference-based Health
      Utilities Index (HUI) instrument HUI23S4.15Q designed for self-report, and
      physical activity was quantified by the Habitual Activity Estimation Scale.
      RESULTS: The mean utility scores for overall HRQL (HUI2 = 0.88, HUI3 = 0.83) were
      similar to those in the Canadian and US general population segments of equivalent
      age (HUI2 = 0.86, HUI3 = 0.85). However, the minimum scores (HUI2 = 0.23, HUI3 = 
      0.09) revealed a group of survivors with notable disabilities in the attributes
      of hearing, emotion, cognition, and pain. There were no statistically significant
      correlations between HRQL and BMI or between HRQL and physical activity, except
      for deafness and inactivity on weekdays. CONCLUSIONS: Overall, long-term
      survivors of ALL in childhood enjoy good HRQL but some experience appreciable
      disability, though this is not associated with BMI or, in the main, with physical
      activity.

PMID- 27885547
TI  - Identifying High Ability Children with DSM-5 Autism Spectrum or Social
      Communication Disorder: Performance on Autism Diagnostic Instruments.
AB  - This study was a replication of Mazefsky et al.'s (Journal of Autism and
      Developmental Disabilities 43:1236-1242, 2013) investigation among a sample of 45
      high ability children and adolescents diagnosed with ASD under DSM-IV-TR. Items
      from the ADOS and ADI-R were mapped onto DSM-5 diagnostic criteria for ASD and
      SCD to determine whether participants would meet either diagnosis under DSM-5. If
      the ADOS were administered alone, 62% of individuals diagnosed with ASD would no
      longer meet criteria under DSM-5; however, when the ADI-R and ADOS scores were
      combined, 100% of individuals would continue to meet ASD diagnosis. The ADOS was
      determined to be an insufficient measure for SCD due to the small number of
      algorithm items measuring SCD diagnostic criteria, suggesting the development of
      SCD measures is required.

PMID- 27885549
TI  - Memory Reconsolidation.
AB  - Scientific advances in the last decades uncovered that memory is not a stable,
      fixed entity. Apparently stable memories may become transiently labile and
      susceptible to modifications when retrieved due to the process of
      reconsolidation. Here, we review the initial evidence and the logic on which
      reconsolidation theory is based, the wide range of conditions in which it has
      been reported and recent findings further revealing the fascinating nature of
      this process. Special focus is given to conceptual issues of when and why
      reconsolidation happen and its possible outcomes. Last, we discuss the potential
      clinical implications of memory modifications by reconsolidation.

PMID- 27885551
TI  - Condomless Sex Among Homeless Youth: The Role of Multidimensional Social Norms
      and Gender.
AB  - Most studies of condomless sex among homeless youth have focused on peer norms,
      while excluding other potentially pertinent influences. This study explored how
      different types of relationships contributed to norms about condomless sex and
      whether such norms were associated with engagement in condomless sex among
      homeless youth. Additionally, because recent work has noted gender differences in
      social networks of male and female homeless youth, gender differences in social
      network norms of condomless sex were also assessed. Egocentric network data were
      collected from homeless youth accessing services at two drop-in centers in Los
      Angeles, CA (N = 976). Multivariate analyses (non-stratified and stratified by
      gender) assessed associations between descriptive, injunctive, and communicative
      norms and participants' engagement in condomless sex. Multivariate analyses
      indicated that perception of peer condom use and communication with sexual
      partners were significantly associated with not engaging in condomless sex. These
      relationships, however, varied by gender. Implications for interventions are
      discussed.

PMID- 27885552
TI  - PrEP Awareness, Familiarity, Comfort, and Prescribing Experience among US Primary
      Care Providers and HIV Specialists.
AB  - HIV pre-exposure prophylaxis (PrEP) was FDA approved in 2012, but uptake remains
      low. To characterize what would facilitate health care providers' increased PrEP
      prescribing, we conducted a 10-city, online survey of 525 primary care providers
      (PCPs) and HIV providers (HIVPs) to assess awareness, knowledge, and experience
      with prescribing PrEP; and, comfort with and barriers to PrEP-related activities.
      Fewer PCPs than HIVPs had heard of PrEP (76 vs 98%), felt familiar with
      prescribing PrEP (28 vs. 76%), or had prescribed it (17 vs. 64%). PCPs were less
      comfortable than HIVPs with PrEP-related activities such as discussing sexual
      activities (75 vs. 94%), testing for acute HIV (83 vs. 98%), or delivering a new
      HIV diagnosis (80 vs. 95%). PCPs most frequently identified limited knowledge
      about PrEP and concerns about insurance coverage as prescribing barriers. PCPs
      and HIVPs differ in needs that will facilitate their PrEP prescribing. Efforts to
      increase PrEP uptake will require interventions to increase the knowledge,
      comfort, and skills of providers to prescribe PrEP.

PMID- 27885553
TI  - Biosimilars for the Treatment of Chronic Inflammatory Diseases: A Systematic
      Review of Published Evidence.
AB  - BACKGROUND: Clinicians are required to assimilate, critically evaluate, and
      extrapolate information to support appropriate use of biosimilars across
      indications. OBJECTIVES: The objective of this study was to systematically
      collate all published data in order to assess the weight (quantity and quality)
      of available evidence for each molecule and inform and support healthcare
      decision-making in chronic inflammatory diseases. METHODS: MEDLINE(r), EMBASE(r),
      and ISI Web of Science(r) were searched to September 2015. Selected conference
      proceedings were searched from 2012 to July 2015. Studies disclosing biosimilars
      with unique identifiers were categorized by originator, study type, and
      indication. Risk of bias assessments were performed. Intended copies were
      differentiated as commercially available agents without evidence of rigorous
      comparative biosimilarity evaluations. RESULTS: Proposed biosimilars for
      adalimumab, etanercept, infliximab, and rituximab are reported in the published
      literature. Across indications, approved biosimilars infliximab CT-P13, SB2, and
      etanercept SB4 have published studies involving the largest number of patients or
      healthy subjects (n = 1405, 743, and 734, respectively), mostly in rheumatoid
      arthritis. At data cut-off, only CT-P13 had published data in ankylosing
      spondylitis (n = 250; randomized control trial) and ulcerative colitis/Crohn's
      disease (n = 336; observational studies). Published data were not available for
      ongoing studies in psoriasis patients. Four intended copies were identified in
      published studies (total: n = 1430; n = 1372 in observational studies). Thematic
      analysis of non-empirical publications showed that indication extrapolation
      remains an issue, particularly for gastroenterologists. CONCLUSIONS: While most
      agents display a moderate to high degree of similarity to their originator in the
      published studies identified, large discrepancies persist in the overall amount
      and type of data available in the public domain. Significant gaps exist
      particularly for intended copies, reinforcing the need to maintain a clear
      differentiation between these molecules and true biosimilars.

PMID- 27885554
TI  - Short-term effects of a green coffee extract-, Garcinia c ambogia- and L
      carnitine-containing chewing gum on snack intake and appetite regulation.
AB  - INTRODUCTION: Different studies have assessed the influence of chewing gum to aid
      control of appetite and reduce food intake. PURPOSE: The aims of the present
      study were to evaluate the effects of chewing gum on satiety, food hedonics and
      snack intake and to explore the potential effects of the combination of Garcinia
      c ambogia, green coffee extract and L-carnitine on satiety, when administered in
      a gum format. METHODS: This was a prospective study in which 57 subjects randomly
      received three kinds of treatments, in a crossover design: (1) active gum; (2)
      placebo gum; and (3) no gum. Food preferences and appetite sensations were
      evaluated by means of the Leeds Food Preference Questionnaire and visual analog
      scales. RESULTS: There was a significant reduction in low-fat sweet snack intake
      with placebo gum and the active gum compared to no gum and a reduction in high
      fat sweet snack intake with the active gum compared to placebo gum and no gum.
      Total caloric intake was only reduced in the active gum condition. Both the
      active and placebo gum conditions significantly reduced hunger and prospective
      food consumption and increased fullness compared to no gum and were associated
      with a reduced wanting for sweet food in the LFPQ, consistent in a reduction in
      the relative preference for sweet snacks versus savoury snacks. CONCLUSION: This
      study supports the notion that chewing gum containing nutraceutical products
      might aid in the control over snack intake and reduce hunger sensations.

PMID- 27885556
TI  - Influence of Selenium on the Production of T-2 Toxin by Fusarium poae.
AB  - The objective of this study was to investigate the effects of selenium on the
      production of T-2 toxin by a Fusarium poae strain cultured in a synthetic medium
      containing different concentrations of selenium. The T-2 toxin contents in
      fermentative products were evaluated by a high performance liquid chromatography
      (HPLC). The results showed that the production of T-2 toxin was correlated with
      the concentration of selenium added to the medium. In all three treatments, the
      addition of 1 mg/L selenium to the medium resulted in a lower toxin yield than
      the control (0 mg/L); the yield of the toxin began to increase when selenium
      concentration was 10 mg/L, while it decreased again at 20 mg/L. In summary, T-2
      toxin yield in the fermentative product was affected by the addition of selenium
      to the medium, and a selenium concentration of 20 mg/L produced the maximum
      inhibitory effect of T-2 toxin yield in the fermentative product of F. poae.

PMID- 27885557
TI  - Isolation of Paenibacillus tumbae sp. nov., from the tomb of the emperor Yang of
      the Sui dynasty, and emended description of the genus Paenibacillus.
AB  - A novel strain, designated strain CSA42T, was isolated from the tomb of emperor
      Yang of Sui in Yangzhou, Jiangsu province, China. Strain CSA42T was observed to
      be Gram-stain positive, strictly aerobic, rod-shaped, spore-forming and motile.
      The optimum conditions for growth were found to be 30  degrees C, pH 8.0 and
      without NaCl. Phylogenetic analysis, based on 16S rRNA gene sequences, revealed
      strain CSA42T to be closely related to Paenibacillus larvae DSM 7030T (94.7%),
      Paenibacillus doosanensis CAU 1055T (94.4%) and Paenibacillus gansuensis B518T
      (94.2%). The major cellular fatty acids were identified as anteiso-C15:0, anteiso
      C17:0 and iso-C16:0. MK-8 was found to be the only respiratory quinone. The polar
      lipids were found to be comprised of diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol and two aminophospholipids. The
      cell wall peptidoglycan was found to contain meso-diaminopimelic acid and ribose
      as the only whole cell sugar. The genomic G+C content of strain CSA42T was
      determined to be 47.6 mol%. The low DNA-DNA relatedness values between strain
      CSA42T and the reference strain P. larvae KACC 11540T and many phenotypic
      properties support the classification of strain CSA42T (=KACC 18941T =CCTCC AB
      2016201T) as the type strain of a novel species of the genus Paenibacillus, for
      which the name Paenibacillus tumbae sp. nov. is proposed. An emended description
      of the genus Paenibacillus based on the new data is also given.

PMID- 27885555
TI  - Meat intake, cooking methods and doneness and risk of colorectal tumours in the
      Spanish multicase-control study (MCC-Spain).
AB  - PURPOSE: Although there is convincing evidence that red and processed meat intake
      increases the risk of colorectal cancer (CRC), the potential role of meat cooking
      practices has not been established yet and could partly explain the current
      heterogeneity of results among studies. Therefore, we aimed to investigate the
      association between meat consumption and cooking practices and the risk of CRC in
      a population-based case-control study. METHODS: A total of 1671 CRC cases and
      3095 controls recruited in Spain between September 2008 and December 2013
      completing a food frequency questionnaire with a meat-specific module were
      included in the analyses. Odds ratios (OR) and confidence intervals (CI) were
      estimated by logistic regression models adjusted for known confounders. RESULTS:
      Total meat intake was associated with increased risk of CRC (OR T3-T1 1.41; 95%
      CI 1.19-1.67; p trend < 0.001), and similar associations were found for white,
      red and processed/cured/organ meat. Rare-cooked meat preference was associated
      with low risk of CRC in red meat (ORrare vs. medium 0.66; 95% CI 0.51-0.85) and
      total meat (ORrare vs. medium 0.56; 95% CI 0.37-0.86) consumers, these
      associations being stronger in women than in men. Griddle-grilled/barbecued meat
      was associated with an increased CRC risk (total meat: OR 1.45; 95% CI 1.13
      1.87). Stewing (OR 1.25; 95% CI 1.04-1.51) and oven-baking (OR 1.18; 95% CI 1.00
      1.40) were associated with increased CRC risk of white, but not red, meat.
      CONCLUSIONS: Our study supports an association of white, red,
      processed/cured/organ and total meat intake with an increased risk of CRC.
      Moreover, our study showed that cooking practices can modulate such risk.

PMID- 27885559
TI  - Erratum to: Synergistic effect of programmed cell death protein 1 blockade and
      secondary lymphoid tissue chemokine in the induction of anti-tumor immunity by a
      therapeutic cancer vaccine.

PMID- 27885558
TI  - Aeromonas and Plesiomonas species from scarlet ibis (Eudocimus ruber) and their
      environment: monitoring antimicrobial susceptibility and virulence.
AB  - The present study aimed at evaluating the role of captive scarlet ibises
      (Eudocimus ruber) and their environment as reservoirs of Aeromonas spp. and
      Plesiomonas spp., and analyzing the in vitro antimicrobial susceptibility and
      virulence of the recovered bacterial isolates. Thus, non-lactose and weak-lactose
      fermenting, oxidase positive Gram-negative bacilli were recovered from cloacal
      samples (n = 30) of scarlet ibises kept in a conservational facility and from
      water samples (n = 30) from their environment. Then, the antimicrobial
      susceptibility, hemolytic activity and biofilm production of the recovered
      Aeromonas spp. and Plesiomonas shigelloides strains were assessed. In addition,
      the virulence-associated genes of Aeromonas spp. were detected. Ten Aeromonas
      veronii bv. sobria, 2 Aeromonas hydrophila complex and 10 P. shigelloides were
      recovered. Intermediate susceptibility to piperacillin-tazobactam and cefepime
      was observed in 2 Aeromonas spp. and 1 P. shigelloides, respectively, and
      resistance to gentamicin was observed in 4 P. shigelloides. The automated
      susceptibility analysis revealed resistance to piperacillin-tazobactam and
      meropenem among Aeromonas spp. and intermediate susceptibility to gentamicin
      among P. shigelloides. All Aeromonas isolates presented hemolytic activity, while
      3 P. shigelloides were non-hemolytic. All Aeromonas spp. and 3/10 P. shigelloides
      were biofilm-producers, at 28  degrees C, while 10 Aeromonas spp. and 6/10 P.
      shigelloides produced biofilms, at 37  degrees C. The most prevalent virulence
      genes of Aeromonas spp. were asa1 and ascV. Scarlet ibises and their environment
      harbour potentially pathogenic bacteria, thus requiring monitoring and measures
      to prevent contamination of humans and other animals.

PMID- 27885560
TI  - Expression of human endogenous retrovirus K and W in babies.
AB  - Here we determined the relative expression of HERV-K and W proviruses in HIV
      infected and non-infected mothers as well as their respective babies up to 1 year
      old. HIV-infected mothers, their babies and uninfected control groups presented
      expression of both HERV-K and HERV-W with relatively high frequency. While the
      level of HERV-K expression was similar among groups, the level of HERV-W
      expression in HIV-infected mothers was four-fold higher than the uninfected
      mothers from the control group (p < 0.01). HERV-W was down regulated in HIV
      exposed babies in comparison to non-exposed babies. To our knowledge, this is the
      first report of HERV transcriptional activity in babies from 0-1 year-old.

PMID- 27885562
TI  - Respiratory syncytial virus and influenza are the key viral pathogens in children
      <2 years hospitalized with bronchiolitis and pneumonia in Islamabad Pakistan.
AB  - Pneumonia remains a leading cause of morbidity and mortality in developing
      countries. Comprehensive surveillance data are needed to review the prevention
      and control strategies. We conducted active surveillance of acute lower
      respiratory infections among children aged <2 years hospitalized at two hospitals
      of Islamabad, Pakistan. Viral etiology was determined using real-time PCR on
      respiratory specimens collected during March 2011-April 2012. The overall mean
      age was 7.83 +/- 5.25 months while no statistical difference between age or sex
      distribution of patients with positive and negative viral etiology (p > 0.05).
      The average weight of the study group was 6.1 +/- 2.25 kg. >=1 viral pathogens
      were detected in 75% cases. Major respiratory viruses included RSV-A: 44%, RSV-B:
      23%, Influenza-A: 24.5%, Influenza-B: 7%, Adenovirus: 8.4% and HmPV: 5.2%. A
      single, dual or multiple viral pathogens were detected in 43%, 27% and 5.2%
      patients respectively. Common symptoms were cough (95%), apnoea (84%), fever
      (78%), wheeze (64.5%), nasal congestion (55%) and rhinorrhea (48%). Among the RSV
      positive cases, 2-6 months age group had highest detection rate for RSV-A (30%, n
      = 21/69) and RSV-B (20%, n = 14/69) while patients infected with Influenza-A were
      in 2.1-6 months age group (61%, 23/38). Statistically significant difference was
      observed between RSV-positive and negative cases for nutrition status (p =
      0.001), cigarette/wood smoke exposure (p = 0.001) and concomitant clinical
      findings. Most patients had successful outcome on combination therapy with
      bronchodilators, inhaled steroids and antibiotics. Our findings underscore high
      burden of ALRI in Pakistan. Interventions targeting viral pathogens coupled with
      improved diagnostic approaches are critical for better prevention and control.

PMID- 27885561
TI  - Outbreak of severe pseudorabies virus infection in pig-offal-fed farmed mink in
      Liaoning Province, China.
AB  - An outbreak of severe pseudorabies virus (PRV) infection in farmed mink occurred
      in northern China in late 2014, causing significant economic losses in the local
      fur industry. Here, we report the first case of a PRV outbreak in mink in
      northeastern China, caused by feeding farmed mink with raw pork or organs
      contaminated by PRV. Mink infected with virulent PRV exhibited diarrhea,
      neurologic signs, and higher mortality, which can be misdiagnosed as highly
      pathogenic mink enteritis virus (MEV), canine distemper virus (CDV), and food
      poisoning. However, these were excluded as causative agents by PCR or bacteria
      isolation. The duration of disease was 3-7 days, and the mortality rate was 80
      90%. PRV was characterized using indirect immunofluorescence assays (IFA) and
      electron microscopy (EM). Phylogenetic analysis based on full-length genome
      sequences and those of individual genes of this novel virus strain showed that it
      clustered in an independent branch with several other PRV isolates from China.

PMID- 27885563
TI  - Quasispecies composition and diversity do not reveal any predictors for chronic
      classical swine fever virus infection.
AB  - Classical swine fever (CSF) can run acute, chronic, and prenatal courses in both
      domestic pigs and wild boar. Although chronic infections are rare events, their
      epidemiological impact is very high due to the long-term shedding of virus. So
      far, little is known about the factors that influence disease course and outcome
      from either the host or virus's perspective. To elucidate the viral determinants,
      we analyzed the role of the viral populations for the development of chronic CSF
      virus (CSFV) infections. Three different animal trials that had led to both
      chronic and acute infections were chosen for a detailed analysis by deep
      sequencing. The three inocula represented sub-genogroups 2.1 and 2.3, and two
      viruses were wild-type CSFV, one derived from an infectious cDNA clone. These
      viruses and samples derived from acutely and chronically infected animals were
      subjected to next-generation sequencing. Subsequently, the derived full-length
      genomes were compared at both the consensus and the quasispecies level. At
      consensus level, no differences were observed between the parental viruses and
      the viruses obtained from chronically infected animals. Despite a considerable
      level of variability at the quasispecies level, no indications were found for any
      predictive pattern with regard to the chronicity of the CSFV infections. While
      there might be no direct marker for chronicity, moderate virulence of some CSFV
      strains in itself seems to be a crucial prerequisite for the establishment of
      long-term infections which does not need further genetic adaption. Thus, general
      host and virus factors need further investigation.

PMID- 27885550
TI  - Neural Activity Patterns Underlying Spatial Coding in the Hippocampus.
AB  - The hippocampus is well known as a central site for memory processing-critical
      for storing and later retrieving the experiences events of daily life so they can
      be used to shape future behavior. Much of what we know about the physiology
      underlying hippocampal function comes from spatial navigation studies in rodents,
      which have allowed great strides in understanding how the hippocampus represents
      experience at the cellular level. However, it remains a challenge to reconcile
      our knowledge of spatial encoding in the hippocampus with its demonstrated role
      in memory-dependent tasks in both humans and other animals. Moreover, our
      understanding of how networks of neurons coordinate their activity within and
      across hippocampal subregions to enable the encoding, consolidation, and
      retrieval of memories is incomplete. In this chapter, we explore how information
      may be represented at the cellular level and processed via coordinated patterns
      of activity throughout the subregions of the hippocampal network.

PMID- 27885564
TI  - Hepatitis E virus infection in patients on dialysis and in solid organ transplant
      recipients in Argentina: exploring associated risk factors.
AB  - Infection with hepatitis E virus (HEV) leads to acute hepatitis infection in
      immunocompetent hosts. HEV genotype 3 can present with high frequency and lead to
      chronic infection in individuals with a compromised immune system. The risk
      factors related to increased seroprevalence or chronicity in this population are
      not entirely understood. Moreover, most studies addressing risk factors for HEV
      in non-endemic areas come from developed areas such as North America and Europe.
      In this study we evaluated seroprevalence, chronicity and risk factors for HEV in
      120 transplant recipients and 88 patients on dialysis in Argentina. We found a
      significantly higher seroprevalence of HEV IgG in those undergoing dialysis
      compared with healthy controls (10.2% and 4.3% respectively, p = 0.03). No
      difference in HEV seroprevalence was observed between healthy controls and
      transplant recipients (5.8%). We found no association between previously
      identified risk factors for HEV, such as pork consumption or use of tacrolimus,
      and HEV seroprevalence. In univariate and multivariate analyses, consumption of
      fish was associated with higher seroprevalence of HEV (OR = 9.33; 95% CI: 2.07
      42.2; p = 0.04). None of the samples showed HEV RNA amplification, indicating
      that chronicity does not seem to be an issue in these cohorts. Our results show
      increased seroprevalence of HEV in individuals undergoing dialysis but not in
      transplant recipients. We also found that fish consumption can be a potential
      risk factor for acquiring HEV.

PMID- 27885565
TI  - Analysis of bacterial, fungal and archaeal populations from a municipal
      wastewater treatment plant developing an innovative aerobic granular sludge
      process.
AB  - Mature granules and flocs from aerobic sludge were collected from the wastewater
      treatment plant (WWTP) treating both municipal and industrial effluents in
      Haining city China. This plant has been operating under conditions favoring
      aerobic granular sludge formation, for over 3 years, suggesting that the
      granules, which stably retained under changing effluent conditions, may contain
      unique microbial populations. Microbial analysis indicated that the granular
      sludge was primarily composed of Planctomycetes, Proteobacteria and Bacteroidetes
      from the bacterial phyla. Interestingly, microbial communities were also observed
      to be stratified between the structural features of the sludge. For example,
      Euryarchaeota was found to make up the majority of the archaea found in the
      granules while Methanosaeta was dominant in the flocs. Additionally, granules
      were found to contain, 34 phyla and 222 genera of bacteria, 4 phyla and 13 genera
      of fungi, and 2 phyla and 17 genera of archaea. While flocs contained, 32 phyla
      and 203 genera of bacteria, 6 phyla and 26 genera of fungi, and 2 phyla and 12
      genera of archaea. This biodiversity signifying a preservation of bacterial and
      archaeal population in granules, and fungal populations in flocs may result from
      the sedimentary characteristics of the granules. This suggests microbes uniquely
      associated in the granules are playing a key role in structure formation and
      stability of the granular ecosystem, which is maintained by the longer sludge
      retention time.

PMID- 27885566
TI  - Vertical zonation of soil fungal community structure in a Korean pine forest on
      Changbai Mountain, China.
AB  - Changbai Mountain, with intact montane vertical vegetation belts, is located at a
      sensitive area of global climate change and a central distribution area of Korean
      pine forest. Broad-leaved Korean pine mixed forest (Pinus koraiensis as an
      edificator) is the most representative zonal climax vegetation in the humid
      region of northeastern China; their vertical zonation is the most intact and
      representative on Changbai Mountain. In this study, we analyzed the composition
      and diversity of soil fungal communities in the Korean pine forest on Changbai
      Mountain at elevations ranging from 699 to 1177 m using Illumina High-throughput
      sequencing. We obtained a total 186,663 optimized sequences, with an average
      length of 268.81 bp. We found soil fungal diversity index was decreased with
      increasing elevation from 699 to 937 m and began to rise after reaching 1044 m;
      the richness and evenness indices were decreased with an increase in elevation.
      Soil fungal compositions at the phylum, class and genus levels varied
      significantly at different elevations, but with the same dominant fungi. Beta
      diversity analysis indicated that the similarity of fungal communities decreased
      with an increased vertical distance between the sample plots, showing a distance
      decay relationship. Variation partition analysis showed that geographic distance
      (mainly elevation gradient) only explained 20.53 % of the total variation of
      fungal community structure, while soil physicochemical factors explained 69.78 %.

PMID- 27885567
TI  - Biodegradation of feather waste keratin by a keratinolytic soil fungus of the
      genus Chrysosporium and statistical optimization of feather mass loss.
AB  - This paper assesses the ability of strains of Aphanoascus fulvescens and
      Chrysosporium articulatum isolated from soil (phaesol) to degrade native feather
      keratin. Strains were identified based on phenotypic traits and nucleotide
      sequencing. Response Surface Methodology was used to optimize cultivation
      conditions exhibiting the highest keratinolytic activity. The experiments were
      based on Box-Behnken designs for the loss of substrate mass (chicken feathers).
      While substrate mass loss is an "economic coefficient" that reliably indicates
      feather keratin degradation, it has not been studied before. Stationary liquid
      cultures of five selected strains were conducted in laboratory conditions at 28 
      degrees C using poultry feathers (1 g) as the sole source of carbon, nitrogen and
      energy. Enzymatic activities, keratin mineralization products and substrate mass
      loss were determined periodically. The mineralization of keratin proteins by
      strains yielded a high number of ammonium ions alkalinizing the medium. Increased
      ammonium ions inhibited the activity of caseinian protease and keratinase. A
      decrease in the concentration of these ions induced proteolytic enzymes, chiefly
      the activity of keratinase, at the end of fungal cultivation. Keratinase activity
      was related to protein- and peptide release and that of caseinian protease to
      sulfate ions. The highest loss of substrate mass in comparison to the reference
      strain CBS104.62 (35.4%) was recorded for Aphanoascus fulvescens B21/4-5 (65.9%).
      Based on a Box-Behnken design, the maximum loss of substrate mass for the
      Aphanoascus fulvescens strain (71.08%) can be achieved at pH 7.58 and temperature
      28.7  degrees C.

PMID- 27885568
TI  - Massive internal jugular vein tumor thrombus derived from squamous cell carcinoma
      of the head and neck: two case reports.
AB  - PURPOSE: Tumor thrombosis of the internal jugular vein (IJV) is an extremely rare
      disease, and the reported cases have been exclusively associated with
      differentiated thyroid cancer. In the present study, we describe two cases of IJV
      tumor thrombosis originated from squamous cell carcinoma (SCC), which is the
      first case report. METHODS: Case 1 was a 67-year-old man diagnosed with advanced
      supraglottic SCC with a massive tumor thrombus in the IJV. He was treated with
      bio-radiotherapy followed by radical surgery. Case 2 was a 65-year-old woman who
      underwent radical surgery for SCC of thyroid with tumor thrombosis in the IJV.
      RESULTS: These cases rapidly developed local recurrences and distant metastases
      and died within 10 months after surgery. CONCLUSIONS: IJV tumor thrombosis
      originated from SCC apparently reflects extremely aggressive state of the tumor.
      Recognition and precaution to this condition is essential for the development of
      a clinically effective treatment strategy.

PMID- 27885569
TI  - Delayed retrieval of a displaced maxillary third molar from infratemporal space
      via trans-sinusoidal approach: a case report and the review of the literature.
AB  - AIM: The aim of this case report is to present the trans-sinusoidal pathway used
      to remove a displaced maxillary third molar from the infratemporal fossa and
      review the English literature regarding the techniques used. CASE REPORT: A 21
      year-old male patient was referred with the findings of an oroantral fistula on
      the left maxillary vestibular first molar region and slight restriction of mouth
      opening. The patient underwent a maxillary sinus surgery in order to remove a
      sinus retention cyst via Caldwell-Luc access in a dental clinic 4 years ago. A
      computerized tomography scan showed the inverted third molar to be located in the
      infratemporal fossa, just between zygomatic arch and lateral pterygoid plate. The
      tooth was accessed through the remaining lateral bone defect from the Caldwell
      Luc approach of the lateral sinus wall. The bone defect was extended. The
      posterior bony wall of the maxillary sinus was removed via a surgical burr. After
      that, the displaced tooth was exposed. The tooth was mobilized via Warwick James
      elevator downwards and removed with a forceps. CONCLUSION: Access for surgical
      removal of the tooth from the infratemporal fossa is not only difficult but also
      has potential for morbidity due to the structures running through it. Wide
      incision in the maxillary sulcus and blunt dissection are reported with lower
      success rates and usually necessitate a second intervention via extraoral route.
      Trans-sinusoidal approach might be an old fashioned but relatively successfully
      attempt in the removal of the upper third molars from the infratemporal fossa.
      Considering the time of removal, if no symptoms were present, it is beneficial to
      wait for a couple of weeks thus facilitating development of fibrous surrounding
      around the tooth.

PMID- 27885570
TI  - Neo-Darwinists and Neo-Aristotelians: how to talk about natural purpose.
AB  - This paper examines the points of disagreement between Neo-Darwinian and recent
      Neo-Aristotelian discussions of the status of purposive language in biology. I
      discuss recent Neo-Darwinian "evolutionary" treatments and distinguish three ways
      to deal with the philosophical status of teleological language of purpose:
      teleological error theory, methodological teleology, and Darwinian teleological
      realism. I then show how "non-evolutionary" Neo-Aristotelian approaches in the
      work of Michael Thompson and Philippa Foot differ from these by offering a view
      of purposiveness grounded in life-cycle patterns, rather than in long-term
      evolutionary processes or natural selection. Finally, I argue that the crucial
      difference between Neo-Darwinian and Neo-Aristotelian approaches regards the
      question of whether or not reproduction deserves the status of an "ultimate" aim
      of organisms. I offer reasons to reject the concept of an "ultimate" aim in
      evolutionary biology and to reject the notion that reproduction serves a purpose.
      I argue that evolutionary biology is not in the position to determine what the
      "ultimate" explanation of natural purpose is.

PMID- 27885571
TI  - ?

PMID- 27885572
TI  - Improving tribological and anti-bacterial properties of titanium external
      fixation pins through surface ceramic conversion.
AB  - In this study, an advanced ceramic conversion surface engineering technology has
      been applied for the first time to self-drilling Ti6Al4V external fixation pins
      to improve their performance in terms of biomechanical, bio-tribological and
      antibacterial properties. Systematic characterisation of the ceramic conversion
      treated Ti pins was carried out using Scanning electron microscope, X-ray
      diffraction, Glow-discharge optical emission spectroscopy, nano- and micro
      indentation and scratching; the biomechanical and bio-tribological properties of
      the surface engineered Ti pins were evaluated by insertion into high density bone
      simulation material; and the antibacterial behaviour was assessed with
      Staphylococcus aureus NCTC 6571. The experimental results have demonstrated that
      the surfaces of Ti6Al4V external fixation pins were successfully converted into a
      TiO2 rutile layer (~2 MUm in thickness) supported by an oxygen hardened case (~15
      MUm in thickness) with very good bonding due to the in-situ conversion nature.
      The maximum insertion force and temperature were reduced from 192N and 31.2 
      degrees C when using the untreated pins to 182N and 26.1  degrees C when the
      ceramic conversion treated pins were tested. This is mainly due to the
      significantly increased hardness (more than three times) and the effectively
      enhanced wear resistance of the cutting edge of the self-drilling Ti pins
      following the ceramic conversion treatment. The antibacterial tests also revealed
      that there was a significantly reduced number of bacteria isolated from the
      ceramic conversion treated pins compared to the untreated pins of around 50 %
      after 20 h incubation, P < 0.01 (0.0024). The results reported are encouraging
      and could pave the way towards high-performance anti-bacterial titanium external
      fixation pins with reduced pin-track infection and pin loosing.

PMID- 27885574
TI  - NADPH oxidase-dependent degradation of single-walled carbon nanotubes in
      macrophages.
AB  - Previous studies have shown that carboxylated single-walled carbon nanotubes
      (SWCNTs) could be oxidatively biodegraded by neutrophil myeloperoxidase (MPO) and
      peroxynitrite (ONOO-). However, the biodegradation mechanism of nanotubes in
      macrophages has not been explored enough. Here, we showed that both MPO and ONOO-
      could effectively oxidize SWCNTs to generate shorter and oxidative nanotubes in
      vitro. SWCNTs were significantly degraded in zymosan-stimulated macrophages, and
      the degradation mechanism was dependent on MPO and ONOO--driven oxidative
      pathways of activated macrophages, where NADPH oxidase was found to be a major
      determinant of the biodegradation process. Moreover, the functionalization of IgG
      to SWCNTs could stimulate MPO release and ONOO- formation in macrophages, thereby
      creating the conditions favorable for degradation of nanotubes and subsequently
      contributing to the higher degradation degree of IgG-coated SWCNTs. Therefore,
      our discovery of NADPH oxidase-dependent SWCNTs degradation in activated
      macrophages will open new opportunities for the regulation of SWCNTs fate in
      vivo.

PMID- 27885573
TI  - Poly(gamma-glutamic acid) and poly(gamma-glutamic acid)-based nanocomplexes
      enhance type II collagen production in intervertebral disc.
AB  - Intervertebral disc (IVD) degeneration often leads to low back pain, which is one
      of the major causes of disability worldwide, affecting more than 80% of the
      population. Although available treatments for degenerated IVD decrease symptoms'
      progression, they fail to address the underlying causes and to restore native IVD
      properties. Poly(gamma-glutamic acid) (gamma-PGA) has recently been shown to
      support the production of chondrogenic matrix by mesenchymal stem/stromal cells.
      gamma-PGA/chitosan (Ch) nanocomplexes (NCs) have been proposed for several
      biomedical applications, showing advantages compared with either polymer alone.
      Hence, this study explores the potential of gamma-PGA and gamma-PGA/Ch NCs for
      IVD regeneration. Nucleotomised bovine IVDs were cultured ex vivo upon injection
      of gamma-PGA (pH 7.4) and gamma-PGA/Ch NCs (pH 5.0 and pH 7.4). Tissue metabolic
      activity and nucleus pulposus DNA content were significantly reduced when NCs
      were injected in acidic-buffered solution (pH 5.0). However, at pH 7.4, both
      gamma-PGA and NCs promoted sulphated glycosaminoglycan production and significant
      type II collagen synthesis, as determined at the protein level. This study is a
      first proof of concept that gamma-PGA and gamma-PGA/Ch NCs promote recovery of
      IVD native matrix, opening new perspectives on the development of alternative
      therapeutic approaches for IVD degeneration.

PMID- 27885575
TI  - Administration of Huperzia quadrifariata Extract, a Cholinesterase Inhibitory
      Alkaloid Mixture, has Neuroprotective Effects in a Rat Model of Cerebral Hypoxia
      Ischemia.
AB  - Neonatal hypoxia-ischemia (HI) is an etiologic component of several neurologic
      pathologies associated to cognitive impairment. The mechanisms involved in HI
      induced tissue damage start immediately after HI and extend for days.
      Acetylcholine is an important neurotransmitter in the central nervous system and
      exerts a protector effect on tissue damage by modulating inflammation, and
      cholinesterase inhibitors have shown neuroprotective properties and their action
      are often attributed to inhibition of the immune response. The administration of
      Huperzia quadrifariata alkaloid extract (HqAE), with potent and selective
      cholinesterase inhibitor properties, will reduce the HI induced behavioral
      deficits and tissue damage. A total of 84 newborn Wistar rat pups at post natal
      day 7 (PND7) were subjected to right carotid occlusion followed by 1 h of hypoxia
      (8% of O2) and i.p. injections of saline, vehicle or HqAE (10 mg/kg). Morris
      Water Maze and inhibitory avoidance tests were used to assess the cognitive
      function. Flow cytometry was performed at PND11. Histological analysis was
      performed at PND45. HqAE treatment was able to prevent the HI induced cognitive
      deficits in both tests and, at PND45, histological analysis showed that HqAE
      treatment reduced hippocampus tissue damage. Flow cytometry of the injured
      hippocampus revealed that the treatment was able to reduce cellular death and the
      number of infiltrating T cells. Altogether, these results show the therapeutic
      potential of the Huperzia quadrifariata alkaloid extract to prevent cognitive
      deficits and histological damage caused by neonatal hypoxia-ischemia, probably by
      reducing cellular death and T cell mobilization.

PMID- 27885577
TI  - Distinct Expression of Various Angiogenesis Factors in Mice Brain After Whole
      Brain Irradiation by X-ray.
AB  - Radiation-induced brain injury (RBI) is the most serious complication after
      radiotherapy. However, the etiology of RBI remains elusive. In order to evaluate
      the effect of X-rays on normal brain tissue, adult male BALB/C mice were
      subjected to whole-brain exposure with a single dose of 10 Gy or sham radiation.
      The structure and number of mice brain vessels were investigated 1, 7, 30, 90 and
      180 days after irradiation by H&E staining and immune-fluorescence staining.
      Compared with sham control mice, in addition to morphological changes, a
      significant reduction of microvascular density was detected in irradiated mice
      brains. Whole-brain irradiation also caused damage in tight junction (TJ).
      Increased expression of glial fibrillary acidic protein (GFAP) and vascular
      endothelial growth factor (VEGF) was observed in irradiated mouse brains showed
      by Western Blot. Immune-fluorescence staining results also verified the co
      labeling of GFAP and VEGF after whole-brain irradiation. Furthermore, the protein
      expression levels of other angiogenesis factors, angiopoietin-1 (Ang-1),
      endothelial-specific receptor tyrosine kinase (Tie-2), and angiopoietin-2 (Ang-2)
      in brain were determined by Western Blot. Increased expression of Ang-2 was shown
      in irradiated mouse brains. In contrast, whole-brain irradiation significantly
      decreased Ang-1 and Tie-2 expression. Our data indicated that X-rays induced time
      dependent microvascular injury and activation of astrocytes after whole-brain
      irradiation in mouse brain. Distinct regulation of VEGF/Ang2 and Ang-1/Tie-2 are
      closely associated with RBI, suggesting that angiogenesis interventions might be
      beneficial for patients with RBI.

PMID- 27885578
TI  - EGb-761 Attenuates the Anti-proliferative Activity of Fluoride via DDK1 in PC-12
      Cells.
AB  - EGb-761 is commonly used as a treatment for ischemic brain injury,
      neurodegenerative diseases and some types of tumors (Christen and Maixent, in
      Cell Mol Biol 48(6):601-611, 2002). However, it is unclear whether EGb-761
      affects the proliferation of cells exposed to fluoride. In this study, the
      proliferation and apoptosis of PC-12 cells exposed to fluoride were investigated
      and EGb-761 was used to protect PC-12 cells against the effects of fluoride. We
      found that the canonical Wnt signaling pathway was involved in the anti
      proliferation of PC-12 cells exposed to fluoride. Furthermore, the results also
      showed that EGb-761 could attenuate the anti-proliferative activity of fluoride
      via DDK1 in PC-12 cells. This study may provide a new method for protecting
      against the inhibition of cell proliferation induced by fluoride.

PMID- 27885576
TI  - Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or
      Association?
AB  - The methylated derivative of L-arginine, asymmetric dimethylarginine (ADMA) is
      synthesized in different mammalian tissues including the brain. ADMA acts as an
      endogenous, nonselective, competitive inhibitor of all three isoforms of nitric
      oxide synthase (NOS) and may limit L-arginine supply from the plasma to the
      enzyme via reducing its transport by cationic amino acid transporters. Hepatic
      encephalopathy (HE) is a relatively frequently diagnosed complex neuropsychiatric
      syndrome associated with acute or chronic liver failure, characterized by
      symptoms linked with impaired brain function leading to neurological
      disabilities. The L-arginine-nitric oxide (NO) pathway is crucially involved in
      the pathomechanism of HE via modulating important cerebral processes that are
      thought to contribute to the major HE symptoms. Specifically, activation of this
      pathway in acute HE leads to an increase in NO production and free radical
      formation, thus, contributing to astrocytic swelling and cerebral edema.
      Moreover, the NO-cGMP pathway seems to be involved in cerebral blood flow (CBF)
      regulation, altered in HE. For this reason, depressed NO-cGMP signaling
      accompanying chronic HE and ensuing cGMP deficit contributes to the cognitive and
      motor failure. However, it should be remembered that ADMA, a relatively little
      known element limiting NO synthesis in HE, may also influence the NO-cGMP pathway
      regulation. In this review, we will discuss the contribution of ADMA to the
      regulation of the NO-cGMP pathway in the brain, correlation of ADMA level with
      CBF and cognitive alterations observed during HE progression in patients and/or
      animal models of HE.

PMID- 27885579
TI  - An integrated assessment of pollution and biological effects in flounder, mussels
      and sediment in the southern Baltic Sea coastal area.
AB  - Organic and metal contaminants and biological effects were investigated in
      flounder, mussels, and sediments in the southern Baltic Sea coastal area in order
      to assess environmental quality status in that area. Four sites were selected,
      including two within the Gulf of Gdansk (GoG). In biota and sediment at each
      site, DDTs dominated over PCBs and PBDEs were the least abundant among organic
      contaminants. Their concentrations decreased progressively outward from GoG.
      Among metal contaminants, the levels of Hg, Pb, and Cd were elevated in GoG.
      Biomarkers in flounder, EROD activity and DNA SB, showed moderate positive
      correlations with organic and metal contaminants. In flounder, the integrated
      biomarker index (IBR/n) presented a spatial trend coherent with chemical
      pollution index (CPI), but there was no clear spatial correspondence between
      IBR/n and CPI in mussels nor between sediment toxicity index (STI) and sediment
      CPI. The integrated assessment of contaminant and biological effect data against
      available assessment criteria indicated that in biota, the contaminant assessment
      thresholds were most often exceeded by CB-118, heptachlor, PBDE, and Hg (in the
      GoG sediments by p,p'-DDT, Hg and Cd), while of the biological determinants, the
      threshold was breeched by AChE activity in mussels in GoG. Applying the
      ICES/OSPAR traffic-light approach showed that of the 50 parameters assessed at
      each site, there were 18% of determinants in the red color category in the two
      GoG sites and 8% of determinants in the two sites outside GoG, which indicated
      that none of the four investigated sites attained good environmental status
      (GES).

PMID- 27885581
TI  - Effects of Praxelis clematidea invasion on soil nitrogen fractions and
      transformation rates in a tropical savanna.
AB  - Plant invasion has been reported to affect a mass of soil ecological processes
      and functions, although invasion effects are often context-, species- and
      ecosystem- specific. This study was conducted to explore potential impacts of
      Praxelis clematidea invasion on contents of total and available soil nitrogen (N)
      and microbial N transformations in a tropical savanna. Soil samples were
      collected from the surface and sub-surface layers in plots with non-, slight, or
      severe P. clematidea invasion in Hainan Province of southern China, which remains
      less studied, and analyzed for contents of the total and available N fractions
      and microbial N transformations. Results showed that total N content
      significantly increased in the surface soil but trended to decrease in the sub
      surface soil in the invaded plots relative to the non-invaded control. Slight
      invasion significantly increased soil alkali-hydrolysable N content in the two
      soil layers. Soil net N mineralization rate was not significantly changed in both
      the soil layers, although soil microbial biomass N was significantly higher in
      plots with severe invasion than the control. There was no significant difference
      in content of soil N fractions between plots with slight and severe invasion. Our
      results suggest that invasion of P. clematidea promotes soil N accumulation in
      the surface soil layer, which is associated with increased microbial biomass N.
      However, the invasion-induced ecological impacts did not increase with further
      invasion. Significantly higher microbial biomass N was maintained in plots with
      severe invasion, implying that severe P. clematidea invasion may accelerate
      nutrient cycling in invaded ecosystems.

PMID- 27885580
TI  - Does the groundwater nitrate pollution in China pose a risk to human health? A
      critical review of published data.
AB  - Nitrate pollution has pervaded many parts of the world, especially in developing
      countries such as China. Based on the available groundwater nitrate data sets in
      China (2000-2015), the groundwater pollution levels at the provincial scale are
      evaluated which contains 33 provinces (units) except for Macau because of lacking
      data. Then, the potential risks posed to human health in national scale are
      quantified. In order to make the results more precise and systematical, both
      drinking and dermal contact exposure pathways are considered, and the influenced
      crowd are more finely divided into four groups to study the impacts of age and
      gender on the outcome, which include infants (0-6 months), children (7 months-17
      years old), adult males (18 years old-), and adult females (18 years old-).
      Results indicate that there are seven units whose groundwater nitrate
      concentrations exceed the standard value with Shaanxi being a seriously poor
      condition. Facing the same level of nitrate, the health risk level changes in the
      order of infants > children > adult males > adult females. That is to say, minors
      and males are more vulnerable compared with adults and females, respectively.
      There is no adverse effect on adult females of the whole country, while gender
      really impacts on the health risk assessment result. Adult males, children, and
      infants face various degrees of health risk respectively in Shaanxi and Shandong,
      which are needed to pay more attention to.

PMID- 27885582
TI  - Biotransformation of herbicides by aquatic microbial communities associated to
      submerged leaves.
AB  - Leaf microbial communities possess a large panel of enzymes permitting the
      breakdown of leaf polymers as well as the transformation of organic xenobiotic
      compounds present in stream waters. This study aims to assess the potential of
      leaf microbial communities, exhibiting different exposure histories to pesticides
      (upstream versus downstream), to biotransform three maize herbicides (mesotrione,
      S-metolachlor, and nicosulfuron) in single and cocktail molecule exposures. The
      results showed a high dissipation of nicosulfuron (sulfonylurea herbicide) (from
      29.1 +/- 10.8% to 66 +/- 16.2%, day 40) in both single and cocktail exposures,
      respectively, but not of mesotrione and S-metolachlor. The formation of
      nicosulfuron metabolites such as ASDM (2-(aminosulfonyl)-N,N-dimethyl-3
      pyridinecarboxamide) and ADMP (2-amino-4,6-dimethoxypyrimidine) and the weak
      sorption (<0.4%) on the leaf matrix confirmed the transformation of this molecule
      by leaf microorganisms. In addition, the downstream communities showed a greater
      ability to transform nicosulfuron than the upstream communities suggesting that
      the exposure history to pesticides is an important parameter and can enhance the
      biotransformation potential of leaf microorganisms. After 40-day single exposure
      to nicosulfuron, the downstream communities were also those experiencing the
      greatest shifts in fungal and bacterial community diversity suggesting a
      potential adaptation of microorganisms to this herbicide. Our study emphasizes
      the importance of leaf microbial communities for herbicide biotransformation in
      polluted stream ecosystems where fungi could play a crucial role.

PMID- 27885583
TI  - Using GIS Mapping to Target Public Health Interventions: Examining Birth Outcomes
      Across GIS Techniques.
AB  - With advances in spatial analysis techniques, there has been a trend in recent
      public health research to assess the contribution of area-level factors to health
      disparity for a number of outcomes, including births. Although it is widely
      accepted that health disparity is best addressed by targeted, evidence-based and
      data-driven community efforts, and despite national and local focus in the U.S.
      to reduce infant mortality and improve maternal-child health, there is little
      work exploring how choice of scale and specific GIS visualization technique may
      alter the perception of analyses focused on health disparity in birth outcomes.
      Retrospective cohort study. Spatial analysis of individual-level vital records
      data for low birthweight and preterm births born to black women from 2007 to 2012
      in one mid-sized Midwest city using different geographic information systems
      (GIS) visualization techniques [geocoded address records were aggregated at two
      levels of scale and additionally mapped using kernel density estimation (KDE)].
      GIS analyses in this study support our hypothesis that choice of geographic scale
      (neighborhood or census tract) for aggregated birth data can alter programmatic
      decision-making. Results indicate that the relative merits of aggregated
      visualization or the use of KDE technique depend on the scale of intervention.
      The KDE map proved useful in targeting specific areas for interventions in cities
      with smaller populations and larger census tracts, where they allow for greater
      specificity in identifying intervention areas. When public health programmers
      seek to inform intervention placement in highly populated areas, however,
      aggregated data at the census tract level may be preferred, since it requires
      lower investments in terms of time and cartographic skill and, unlike
      neighborhood, census tracts are standardized in that they become smaller as the
      population density of an area increases.

PMID- 27885584
TI  - WT1 and NPHS2 gene mutation analysis and clinical management of steroid-resistant
      nephrotic syndrome.
AB  - Nephrotic syndrome (NS) is a kidney disease predominantly present in children
      with idiopathic condition; final stage of the disease progresses into end-stage
      renal disease. Generally, NS is treated using standard steroid therapy, however;
      most of the children are steroid sensitive and about 15-20% are non-responders
      (SRNS). Non-responsiveness of these children would be a risk with the possibility
      of mutational changes in podocyte genes (NPHS1, NPHS2, WT1, PLCE1). The mutation
      in podocyte genes is associated with SRNS. NPHS1, NPHS2, and WT1 genes are
      identified/directly linked to SRNS. The present study is a surveillance on the
      mutation analysis of WT1 (exons 8 and 9) and NPHS2 (exons 1-8) gene in SRNS
      followed by clinical management. In the present study, we analyzed these two
      genes in a total of 117 SRNS (73 boys and 44 girls) children. A total of five
      mutations were detected in six children. First, WT1 mutation was detected at 9th
      intron-IVS 9 + 4C > T position in one SRNS female patient. This WT1 mutation was
      identified in a girl having Frasier Syndrome (FS) with focal segmental
      glomerulosclerosis and a complete sex reversal found through molecular and
      karyological screening. In NPHS2, missense mutations of P20L (in two children),
      P316S, and p.R229Q, and a frame shift mutation of 42delG were detected. Thus,
      applying molecular investigation helped us to decide on treatment plan of SRNS
      patients, mainly to avoid unnecessary immunosuppressive treatment.

PMID- 27885587
TI  - Assaults against U.S. law enforcement officers in the line-of-duty: situational
      context and predictors of lethality.
AB  - BACKGROUND: Research on occupational safety of law enforcement officers (LEOs)
      has primarily focused on fatal assaults. Nonfatal assaults, however, have
      received little attention. The goal of this study was to describe the situational
      contexts in which LEOs are assaulted, and compare these contexts and risks
      between fatal and nonfatal assaults in the U.S. Analyzing both types of assaults
      provides a more complete understanding of occupational safety and opportunities
      for intervention. METHODS: This study includes a descriptive epidemiology of
      fatal and nonfatal assaults of LEOs in the U.S. and a pooled cross-sectional
      analysis of risk factors contributing to the odds of lethal assault. Data were
      collected from the Law Enforcement Officers Killed and Assaulted database.
      Descriptive statistics were used to characterize fatal and nonfatal assaults.
      Odds ratios were generated to understand the odds that an assault would result in
      a fatality. RESULTS: Between 1998 and 2013, there were 791 fatal assaults and
      2,022 nonfatal assaults of LEOs. Nearly 60% of primary wounds in fatal assaults
      were received to the head, neck, or throat while nearly 50% of primary wounds in
      nonfatal assaults were received to the arms/hands or below the waist. The odds
      that an assault resulted in a fatality decreased by 57% (OR 0.43, 95% CI 0.32 to
      0.58) when a LEO was wearing body armor. LEOs experiencing an ambush or
      unprovoked attack had significantly increased odds of an assault resulting in a
      fatality (OR 3.27, 95% CI 1.83 to 5.85 and OR 2.24, 95% CI 1.44 to 3.47
      respectively). LEOs that were disarmed during an encounter with a suspect had
      more than 2-fold increased odds of an assault resulting in a fatality (OR 2.24,
      95% CI 1.48 to 3.38). CONCLUSIONS: There are specific situational and encounter
      characteristics that influence the lethality of an assault, which suggest
      strategies for prevention. Mandatory wear policies for the use of body armor
      could significantly reduce mortality among assaulted LEOs.

PMID- 27885585
TI  - The conundrums of chronic kidney disease and aging.
AB  - Chronic kidney disease (CKD), as presently defined, is a common disorder. Aging
      is a nearly universal phenomenon that can affect renal anatomy and function, but
      at variable rates in individuals. Loss of nephrons and a decline in glomerular
      filtration rate (GFR) is a characteristic of normal aging, called renal
      senescence. Using fixed and absolute thresholds for defining CKD on the basis of
      GFR for all ages may lead to diagnostic uncertainty (a conundrum) in both young
      and older subjects. This brief review will consider the physiological and
      anatomical changes of the kidney occurring in the process of normal renal
      senescence focusing on GFR and will examine the relevance of these observation
      for the diagnosis of CKD using GFR as the distinguishing parameter. Once a better
      understanding of the pathobiology underlying renal senescence is obtained,
      specific interventions may become available to slow the process.

PMID- 27885586
TI  - An in vitro comparison of three delivery techniques for obturation of root canals
      in primary molars.
AB  - AIM: This in vitro study evaluated the efficacy of three different obturation
      techniques with regards to quality of two filling pastes-Ca(OH)2/iodoform syringe
      paste and zinc oxide eugenol paste in primary molars. METHODS: Root canals of 45
      extracted primary molars were prepared and randomly divided into three groups of
      15 teeth each. Group A-canals were filled with Ca(OH)2/iodoform syringe paste,
      Group B-zinc oxide eugenol paste with handheld lentulo spiral and Group C-zinc
      oxide eugenol paste with rotary lentulo spiral. The quality of filled root canals
      was evaluated with conventional radiography in antero-posterior and lateral
      dimensions. RESULTS: There were significant differences between all groups in the
      presence of voids (p = 0.03) and length of filling (p = 0.002). Half of the
      sampled teeth in handheld lentulo spiral group had voids in the filled canals,
      while 80% of the teeth filled with Ca(OH)2/iodoform syringe resulted in
      overfilling of the paste. CONCLUSIONS: All three delivery methods for the
      obturation of primary molars' root canals showed inherent limitations in terms of
      voids and quality of filling. Voids are inevitable and were present in all the
      techniques. Overfilling was more frequently seen with the syringe method, while
      the lentulo spiral technique, both handheld and rotary, showed a better quality
      of filling.

PMID- 27885588
TI  - A mouse model reveals that Mfsd2a is critical for unfolded protein response upon
      exposure to tunicamycin.
AB  - Major facilitator superfamily domain containing 2a (Mfsd2a) is a member of the
      major facilitator superfamily. Mfsd2a functions as a transporter for
      docosahexaenoic acid and also plays a role in the unfolded protein response (UPR)
      upon tunicamycin (TM) exposure. UPR is involved in the pathogenesis of various
      human diseases. TM and thapsigargin are representative experimental reagents that
      induce UPR. To elucidate the detailed function of Mfsd2a in UPR in vivo, we
      generated Mfsd2a-deficient mice and investigated the role of Mfsd2a during UPR
      induced by TM or thapsigargin. Phenotypically, Mfsd2a-deficient mice were small
      and short-lived. No gross anatomical abnormalities in Mfsd2a-deficient mice
      compared with the wild-type mice were exhibited. Embryonic fibroblasts derived
      from Mfsd2a-null mice failed to show induction of GRP78 and DDIT3 expressions
      upon TM exposure but not upon Tg exposure. This phenomenon could not be overcome
      despite the exposure under high TM concentration. Reconstitution of Mfsd2a in
      Mfsd2a-null MEF showed hypersensitivity to TM. Furthermore, we examined the
      physiological role of Mfsd2a against TM using an in vivo mouse model. DDIT3
      induction by TM was drastically attenuated in both the liver and brain of Mfsd2a
      deficient mice. These results reveal that Mfsd2a plays a critical role in UPR
      upon TM exposure.

PMID- 27885589
TI  - Organic Cocrystals: New Strategy for Molecular Collaborative Innovation.
AB  - Organic cocrystals that are composed of two or more components usually exhibit
      novel, unpredictable, and even unique properties rather than a simple combination
      of the properties of their components, such as white-light emission, ambipolar
      charge transport, nonlinear optics, and ferroelectricity. Since cocrystal
      engineering represents a novel strategy for synthesizing multifunctional
      materials, which opens the door for molecular collaborative innovation, it has
      aroused much attention in recent years. However, as it is also a relatively new
      research field, it is only in its early stages of development. In order to
      provide readers with an understanding of the future design of cocrystals for
      potential applications, a brief review of organic cocrystals is presented here,
      including an introduction to organic cocrystals as well as discussions of
      cocrystal preparation, methods and techniques of characterization, and
      multifunctional applications of cocrystals. Moreover, the outlook for further
      studies and applications of cocrystal engineering is considered.

PMID- 27885590
TI  - Payment Reform Needed to Address Health Disparities of Undiagnosed Diabetic
      Retinopathy in the City of Chicago.
AB  - INTRODUCTION: The Affordable Care Act (ACA) has expanded health coverage for
      thousands of Illinois residents. Expanded coverage, however, does not guarantee
      appropriate health care. Diabetes and its ocular complications serve as an
      example of how providers in underserved urban areas may not be able to keep up
      with new demand for labor- and technology-intensive health care unless changes in
      reimbursement policies are instituted. METHODS: A retrospective cohort study was
      conducted using medical encounter information from the Chicago HealthLNK Data
      Repository (HDR), an assembly of non-duplicated and de-identified patient medical
      records. We used a method of estimating the geographic distribution of
      undiagnosed diabetic retinopathy in the city of Chicago to illustrate the
      magnitude of potentially preventable eye disease. All rates were calculated for
      all ZIP Codes within Chicago (Cook County), and statistical differences between
      observed and geographically adjusted expected rates (p < 0.10, p < 0.05, p <
      0.01) were highlighted as underserved areas. RESULTS: This analysis included
      150,661 patients with diabetes identified from a total of nearly two million
      patients in Chicago. High rates of undetected diabetic retinopathy were found in
      low-income and minority areas. Within these areas, 37% of the identified
      diabetics were uninsured, with rates ranging widely from 20% to 68.6%. Among
      those with insurance, 32.8% were covered by Medicare and only 10% by Medicaid.
      Most patients with untreated diabetic retinopathy were found to reside in areas
      where primary health care is provided through Federally Qualified Health Centers.
      CONCLUSIONS: With 150,661 diabetics identified in the city of Chicago, and this
      number continuing to rise each year, a manpower approach with ophthalmologist
      screening for diabetic retinopathy is not realistic. The ability to identify the
      growing number of diabetic patients with retinopathy in low-income areas will
      likely require the adoption of cost-effective screening technologies that are
      currently not funded by Medicare and Medicaid.

PMID- 27885591
TI  - The Impact of Non-Steroidal Anti-Inflammatory Agents after Phacoemulsification on
      Quality of Life: A Randomized Study.
AB  - INTRODUCTION: The purpose of our study was to investigate the impact of ketorolac
      addition to the well-established combination of antibiotic-steroid agent in terms
      of vision-related quality of life. METHODS: Patients were randomized to: (1)
      fixed combination of tobramycin 0.3%-dexamethasone 0.1%, one drop qid (n = 68)
      and (2) fixed combination of tobramycin 0.3%-dexamethasone 0.1%, one drop qid,
      plus ketorolac tromethamine 0.5%, one drop tid (n = 70). All patients completed
      the VFQ-25 questionnaire to assess their functional vision before cataract
      surgery and postoperatively on days 7, 28 and 42. The statistical analysis
      comprised the point-wise comparison between the two groups at the four time
      points for all sub-scales of the VFQ-25 questionnaire, as well as the composite
      score. RESULTS: No significant differences were noted regarding the composite
      score, as well as all subscales in all examined time points. CONCLUSIONS: The
      addition of ketorolac did not seem to offer any additional benefit in terms of
      vision-related quality of life.

PMID- 27885592
TI  - Normal Threshold Size of Stimuli in Children Using a Game-Based Visual Field
      Test.
AB  - INTRODUCTION: The aim of this study was to demonstrate and explore the ability of
      novel game-based perimetry to establish normal visual field thresholds in
      children. METHODS: One hundred and eighteen children (aged 8.0 +/- 2.8 years old)
      with no history of visual field loss or significant medical history were
      recruited. Each child had one eye tested using a game-based visual field test
      'Caspar's Castle' at four retinal locations 12.7 degrees  (N = 118) from
      fixation. Thresholds were established repeatedly using up/down staircase
      algorithms with stimuli of varying diameter (luminance 20 cd/m2, duration 200 ms,
      background luminance 10 cd/m2). Relationships between threshold and age were
      determined along with measures of intra- and intersubject variability. RESULTS:
      The Game-based visual field test was able to establish threshold estimates in the
      full range of children tested. Threshold size reduced with increasing age in
      children. Intrasubject variability and intersubject variability were inversely
      related to age in children. CONCLUSIONS: Normal visual field thresholds were
      established for specific locations in children using a novel game-based visual
      field test. These could be used as a foundation for developing a game-based
      perimetry screening test for children.

PMID- 27885593
TI  - Campylobacter jejuni Isolation/Enumeration from Environmental Samples.
AB  - Currently, there is no universally accepted standard media or method for the
      recovery of Campylobacter species. This is likely due to the ubiquity of the
      organism in nature, the complex sample matrices from which the organism is often
      recovered, as well as the fragile/viable-but nonculturable state the organism
      assumes in response to stress. The use of a sterile filter placed upon a
      nonselective Brucella Agar Blood Plate (BAB), followed by incubation at 37 
      degrees C in a hydrogen-containing atmosphere (Campycheck), is one method to
      recover stressed and emerging Campylobacter spp. from complex environmental
      matrices; however, this technique does not currently allow for the enumeration of
      the recovered organisms. Enumeration is performed using serial dilutions of
      sample homogenate plated onto modified Campy-Cefex media followed by incubation
      at either 37  degrees C or 42  degrees C in a microaerobic atmosphere.

PMID- 27885595
TI  - Methods for Isolation, Purification, and Propagation of Bacteriophages of
      Campylobacter jejuni.
AB  - Here, we describe the methods for isolation, purification, and propagation of
      Campylobacter jejuni bacteriophages from samples expected to contain high number
      of phages such as chicken feces. The overall steps are (1) liberation of phages
      from the sample material; (2) observation of plaque-forming units on C. jejuni
      lawns using a spot assay; (3) isolation of single plaques; (4) consecutive
      purification procedures; and (5) propagation of purified phages from a plate
      lysate to prepare master stocks.

PMID- 27885594
TI  - Recovery of Campylobacter spp. from Food and Environmental Sources.
AB  - The recovery of Campylobacter species from food and environmental sources is
      challenging due to the slow growth of these bacteria and the need to suppress
      competing organisms during the isolation procedures. The addition of multiple
      selective antimicrobials to growth media can negatively impact recovery of some
      Campylobacter spp. Here, we describe our current method for the isolation of
      thermotolerant Campylobacter species, mainly C. jejuni and C. coli, from food and
      environmental samples. We emphasize the use of membrane filtration during plating
      for the specific isolation of Campylobacter spp. and a reduced use of
      antimicrobial supplements throughout the whole isolation process.

PMID- 27885596
TI  - Methods to Study Antimicrobial Resistance in Campylobacter jejuni.
AB  - Campylobacter jejuni is a leading bacterial cause of foodborne gastroenteritis
      worldwide and is increasingly resistant to clinically important antibiotics.
      Detection of antibiotic resistance in C. jejuni can be performed with both
      phenotypic and genotypic methods. In this chapter, we describe the most commonly
      used molecular biology methods for detection of resistance to clinically
      important antibiotics. These methods can be employed in both clinical and
      research settings to facilitate clinical therapy and to monitor the emergence and
      dissemination of antibiotic-resistant C. jejuni.

PMID- 27885597
TI  - Method of Peptide Nucleic Acid (PNA)-Mediated Antisense Inhibition of Gene
      Expression in Campylobacter jejuni.
AB  - Peptide nucleic acid (PNA) is an oligonucleotide mimic that recognizes and binds
      to nucleic acids. The strong binding affinity of PNA to mRNA coupled with its
      high sequence specificity enable antisense PNA to selectively inhibit (i.e.,
      knockdown) the protein synthesis of a target gene. This novel technology provides
      a powerful tool for Campylobacter studies because molecular techniques have been
      relatively less well-developed for this bacterium as compared to other pathogens,
      such as Escherichia coli and Salmonella. This chapter describes a protocol for
      PNA-mediated antisense inhibition of gene expression in Campylobacter jejuni.

PMID- 27885598
TI  - Identification of Ligand-Receptor Interactions: Ligand Molecular Arrays, SPR and
      NMR Methodologies.
AB  - Despite many years of research into bacterial chemotaxis, the only well
      characterized system to date is that of E. coli. Even for E. coli, the direct
      ligand binding had been fully characterized only for aspartate and serene
      receptors Tar and Tsr. In 30 years since, no other direct receptor-ligand
      interaction had been described for bacteria, until the characterization of the C.
      jejuni aspartate and multiligand receptors (Hartley-Tassell et al. Mol Microbiol
      75:710-730, 2010). While signal transduction components of many sensory pathways
      have now been characterized, ligand-receptor interactions remain elusive due to
      paucity of high-throughput screening methods. Here, we describe the use of
      microarray screening we developed to identify ligands, surface plasmon resonance,
      and saturation transfer difference nuclear magnetic resonance (STD-NMR) we used
      to verify the hits and to determine the affinity constants of the interactions,
      allowing for more targeted verification of ligands with traditional chemotaxis
      and in vivo assays described in Chapter 13 .

PMID- 27885599
TI  - Characterization of High Affinity Iron Acquisition Systems in Campylobacter
      jejuni.
AB  - Iron acquisition systems are critical for bacterial pathogenesis and thus have
      been proposed as attractive targets for iron-dependent pathogen control. Of these
      systems, high-affinity iron acquisition mediated by siderophore, a small iron
      chelator, is the most efficient iron-scavenging mechanism in gram-negative
      bacteria. Campylobacter does not produce any siderophores but has the ability to
      utilize exogenous siderophores. In particular, the enterobactin (Ent)-mediated
      iron scavenging is tightly linked to Campylobacter pathogenesis. To date, Ent, a
      triscatecholate with the highest known affinity for ferric iron, is a well
      characterized siderophore used by Campylobacter for iron acquisition during in
      vivo infection. Here, we describe the key methods used to characterize Ent
      mediated high affinity iron acquisition system in Campylobacter jejuni.

PMID- 27885600
TI  - Method for the Successful Crystallization of the Ferric Uptake Regulator from
      Campylobacter jejuni.
AB  - The Ferric Uptake Regulator (FUR) is a transcription factor (TF) regulating the
      expression of several genes to control iron levels in prokaryotes. Members of
      this family of TFs share a common structural scaffold that typically comprises
      two regions that include a DNA binding and dimerization domains. While this
      structural organization is conserved, FUR proteins employ different mechanisms to
      bind divergent DNA binding elements and regulate gene expression in the absence
      or presence of regulatory metals. These findings, combined with the observations
      that FUR proteins display different geometries in regard to the relative
      orientation of the DNA binding and dimerization domains, have highlighted an
      expanding repertoire of molecular mechanisms controlling the activity of this
      family of TFs. In this chapter, we present an overview of the methods to purify,
      crystallize, and solve the structure of Campylobacter jejuni FUR.

PMID- 27885601
TI  - Methods for Initial Characterization of Campylobacter jejuni Bacteriophages.
AB  - Here we describe an initial characterization of Campylobacter jejuni
      bacteriophages by host range analysis, genome size determination by pulsed-field
      gel electrophoresis, and receptor-type identification by screening mutants for
      phage sensitivity.

PMID- 27885602
TI  - Methods to Assess the Direct Interaction of C. jejuni with Mucins.
AB  - Studies of the interaction of bacteria with mucus-secreting cells can be
      complemented at a more mechanistic level by exploring the interaction of bacteria
      with purified mucins. Here we describe a far Western blotting approach to show
      how C. jejuni proteins separated by SDS PAGE and transferred to a membrane or
      slot blotted directly onto a membrane can be probed using biotinylated mucin. In
      addition we describe the use of novel mucin microarrays to assess bacterial
      interactions with mucins in a high-throughput manner.

PMID- 27885603
TI  - Methods to Study Campylobacter jejuni Adherence to and Invasion of Host
      Epithelial Cells.
AB  - Measuring bacterial adherence and invasion of cells in vitro has enabled
      researchers to dissect the interactions of Campylobacter jejuni with eukaryotic
      cells. Numerous C. jejuni virulence determinants and host cell factors that
      contribute to the process of adherence, invasion, and immune modulation have been
      identified utilizing in vitro adherence and invasion assays. In this chapter, we
      describe the evaluation of C. jejuni adherence to and invasion of HeLa cells
      using the gentamicin-protection assay.

PMID- 27885605
TI  - Characterization of Ligand-Receptor Interactions: Chemotaxis, Biofilm, Cell
      Culture Assays, and Animal Model Methodologies.
AB  - Chemotactic motility is an essential virulence factor for the pathogenesis of
      Campylobacter spp. infection. In Chapter 6 , we described technologies that
      enable initial screening and identification of ligands able to interact with
      chemoreceptor sensory domains. These include amino acid and glycan arrays, NMR,
      and SPR that are utilized to identify potential ligands interacting with
      Campylobacter jejuni. Here we describe techniques that enable the
      characterization and evaluation of ligand-receptor binding in chemotaxis through
      the assessment of motility and directed chemotactic motility as well as the
      associated phenotypes-autoagglutination behavior, biofilm formation, ability to
      adhere and invade cultured mammalian cells, and colonization ability in avian
      hosts.

PMID- 27885606
TI  - Using Galleria mellonella as an Infection Model for Campylobacter jejuni
      Pathogenesis.
AB  - Nonmammalian model systems of infection have been employed recently to study
      bacterial virulence. For instance, Galleria mellonella (the greater wax moth) has
      been shown to be susceptible to infection by many bacterial pathogens including
      the enteric pathogen Campylobacter jejuni. In contrast to the traditional animal
      models for C. jejuni such as the chick colonization model and ferret diarrheal
      model, the Galleria mellonella infection model has the advantages of lower cost,
      ease of use and no animal breeding is required. However, injecting the larvae
      with bacteria requires care to avoid killing of larvae, which could lead to
      misleading results. Here, we describe the infection of G. mellonella larvae by C.
      jejuni and how to record/interpret results.

PMID- 27885604
TI  - Assays to Study the Interaction of Campylobacter jejuni with the Mucosal Surface.
AB  - Mucosal colonization and overcoming the mucosal barrier are essential steps in
      the establishment of infection by Campylobacter jejuni. The interaction between
      C. jejuni and host cells, including binding and invasion, is thought to be the
      key virulence factor important for pathogenesis of C. jejuni infections in
      animals or humans. The intestinal mucosal barrier is composed of a polarized
      epithelium covered by a thick adherent mucus gel layer. There is a requirement
      for cell culture assays of infection to accurately represent the in vivo mucosal
      surface. In this chapter, we describe the use of a number of cell culture models
      and the use of polarized in vitro organ culture to examine the interaction of C.
      jejuni with mucosal surfaces.

PMID- 27885607
TI  - Mouse Models for Campylobacter jejuni Colonization and Infection.
AB  - Relevant animal models for Campylobacter jejuni infection have been difficult to
      establish due to C. jejuni's inability to cause disease in many common animal
      research models. Fortunately, recent work has proven successful in developing
      several new and relevant mouse models of C. jejuni infection, including the
      SIGIRR-deficient mouse strain that develops acute enterocolitis in response to C.
      jejuni. Here we describe how to properly infect mice with C. jejuni, as well as a
      number of accompanying histological techniques to aid in studying C. jejuni
      colonization and infection in mice.

PMID- 27885608
TI  - Metabolomic Analysis of Campylobacter jejuni by Direct-Injection Electrospray
      Ionization Mass Spectrometry.
AB  - Direct-injection mass spectrometry (DIMS) is a means of rapidly obtaining
      metabolomic phenotype data in both prokaryotes and eukaryotes. Given our
      generally poor understanding of Campylobacter metabolism, the high-throughput and
      relatively simple sample preparation of DIMS has made this an attractive
      technique for metabolism-related studies and hypothesis generation, especially
      when attempting to analyze metabolic mutants with no clear phenotype. Here we
      describe a metabolomic fingerprinting approach with sampling and extraction
      methodologies optimized for direct-injection electrospray ionization mass
      spectrometry (ESI-MS), which we have used as a means of comparing wild-type and
      isogenic mutant strains of C. jejuni with various metabolic blocks.

PMID- 27885609
TI  - Methods for Genome-Wide Methylome Profiling of Campylobacter jejuni.
AB  - Methylation has a profound role in the regulation of numerous biological
      processes in bacteria including virulence. The study of methylation in bacteria
      has greatly advanced thanks to next-generation sequencing technologies. These
      technologies have expedited the process of uncovering unique features of many
      bacterial methylomes such as characterizing previously uncharacterized
      methyltransferases, cataloging genome-wide DNA methylations in bacteria,
      identifying the frequency of methylation at particular genomic loci, and
      revealing regulatory roles of methylation in the biology of various bacterial
      species. For instance, methylation has been cited as a potential source for the
      pathogenicity differences observed in C. jejuni strains with syntenic genomes as
      seen in recent publications. Here, we describe the methodology for the use of
      Pacific Biosciences' single molecule real-time (SMRT) sequencing for detecting
      methylation patterns in C. jejuni and bioinformatics tools to profile its
      methylome.

PMID- 27885610
TI  - Characterizing Glycoproteins by Mass Spectrometry in Campylobacter jejuni.
AB  - The glycosylation systems of Campylobacter jejuni (C. jejuni) are considered
      archetypal examples of both N- and O-linked glycosylations in the field of
      bacterial glycosylation. The discovery and characterization of these systems both
      have revealed important biological insight into C. jejuni and have led to the
      refinement and enhancement of methodologies to characterize bacterial
      glycosylation. In general, mass spectrometry-based characterization has become
      the preferred methodology for the study of C. jejuni glycosylation because of its
      speed, sensitivity, and ability to enable both qualitative and quantitative
      assessments of glycosylation events. In these experiments the generation of
      insightful data requires the careful selection of experimental approaches and
      mass spectrometry (MS) instrumentation. As such, it is essential to have a deep
      understanding of the technologies and approaches used for characterization of
      glycosylation events. Here we describe protocols for the initial characterization
      of C. jejuni glycoproteins using protein-/peptide-centric approaches and discuss
      considerations that can enhance the generation of insightful data.

PMID- 27885611
TI  - Methods for Proteome Analysis of Campylobacter jejuni Using 2-D Electrophoresis.
AB  - This chapter describes protocols used for two-dimensional electrophoretic
      analysis of the proteome or subproteome of Campylobacter jejuni, a major human
      food-borne pathogen. The following protocols, adapted to Campylobacter strains,
      include all the steps from cultivation to gel-support protein separation.

PMID- 27885612
TI  - Analyzing Prokaryotic RNA-Seq Data: A Case Study Identifying Holo-Fur Regulated
      Genes in Campylobacter jejuni.
AB  - In recent years, RNA-seq has become an important method in the process of
      measuring gene expression in various cells and organisms. This chapter will
      detail all the bioinformatic steps that should be undertaken to determine
      differentially expressed genes from a typical RNA-seq experiment. Each step will
      be clearly explained in "non-bioinformatic" terminology so that readers embarking
      on RNA-seq analysis will be able to understand the rationale and reasoning behind
      each step. Moreover, the exact command lines used to process the data will be
      presented along with a description of the various flags and commands.

PMID- 27885613
TI  - Generation and Screening of an Insertion Sequencing-Compatible Mutant Library of
      Campylobacter jejuni.
AB  - The advent of next-generation sequencing technology has enabled experimental
      approaches to characterize large, complex populations of DNA molecules with high
      resolution. Included among these are methods to assess populations of transposon
      insertion libraries for the fitness cost of any particular mutant allele after
      applying selection to a population. These approaches have proven invaluable for
      identifying genetic factors that influence survival of bacterial pathogens within
      different environments, including animal hosts. One such method, termed insertion
      site sequencing (INSeq), was designed to generate a 16 bp fragment of transposon
      flanking genomic DNA captured during the protocol, which then serves as the
      substrate for massively parallel sequencing. Here we describe the generation of a
      transposon mutant library of Campylobacter jejuni amenable to INSeq and its use
      in identifying colonization determinants in a day-of-hatch chicken colonization
      model.

PMID- 27885614
TI  - Family income and body mass index - what have we learned from China.
AB  - Obesity poses lots of health risks in both developing and developed countries.
      One thing that remains unclear is the relationship between family income and
      weight gain. This paper explores the relationship between family income and Body
      Mass Index (BMI) given variations in individual choice towards basic consumption
      and life quality improvement consumption as income increases. We use a nationally
      representative longitudinal data from China, the China Health and Nutrition
      Survey (CHNS), to estimate the relationship between income and weight gain. We
      conduct both cross sectional and panel data analysis to study the causal effects
      of family income on weight development. Unlike other literature that found
      inverse relationship between prevalence of obesity and family income in
      developing countries, in this paper, we find that BMI will first increase with
      family income at a decreasing rate, and then decrease which suggests that the
      group of middle class may suffer the high risk of being overweight and obese.

PMID- 27885615
TI  - The white mullet (Mugil curema) as biological indicator to assess environmental
      stress in tropical coastal lagoons.
AB  - Several coastal lagoons and estuaries in Mexico receive untreated domestic and
      industrial discharges which contain complex mixtures of contaminants. In order to
      assess the effects of chemical contamination, we used the White mullet (Mugil
      curema) as biological indicator. We worked in two estuaries located in Northwest
      Mexico: Urias (highly polluted) and Teacapan (less polluted, therefore used as
      reference site). We measured several endpoints at different levels of biological
      organization: vitellogenin transcription in males as biomarker of estrogenic
      contamination, as well as reproductive, morphological (deformities),
      morphometric, and meristic parameters. Total RNA was isolated from the liver, and
      a partial sequence of the mullet vitellogenin gene was obtained; gene expression
      was analyzed by quantitative PCR. At the same time, gonad samples were analyzed
      by histologic techniques to determine sex ratios and the reproductive cycle
      stage. The reproductive season was detected from February to June in both sites,
      but the gonadosomatic index was consistently higher in Teacapan. Sex ratios were
      female-biased in both estuaries, and one intersex gonad and several malformations
      were found in fish from Urias. Vitellogenin gene transcription in males was
      detected in both sites, although gene expression was slightly higher in Urias.
      The results obtained in this study indicate that biological effects of
      contamination are evident in fish, environmental estrogens may be present in both
      estuaries, and the white mullet is useful as biological indicator to identify and
      characterize environmental stressors in tropical coastal ecosystems.

PMID- 27885616
TI  - Phytoplankton dynamics of a subtropical reservoir controlled by the complex
      interplay among hydrological, abiotic, and biotic variables.
AB  - This study was conducted to identify the key factors related to the
      spatiotemporal variations in phytoplankton abundance in a subtropical reservoir
      from 2006 to 2010 and to assist in developing strategies for water quality
      management. Dynamic factor analysis (DFA), a dimension-reduction technique, was
      used to identify interactions between explanatory variables (i.e., environmental
      variables) and abundance (biovolume) of predominant phytoplankton classes. The
      optimal DFA model significantly described the dynamic changes in abundances of
      predominant phytoplankton groups (including dinoflagellates, diatoms, and green
      algae) at five monitoring sites. Water temperature, electrical conductivity,
      water level, nutrients (total phosphorus, NO3-N, and NH3-N), macro-zooplankton,
      and zooplankton were the key factors affecting the dynamics of aforementioned
      phytoplankton. Therefore, transformations of nutrients and reactions between
      water quality variables and aforementioned processes altered by hydrological
      conditions may also control the abundance dynamics of phytoplankton, which may
      represent common trends in the DFA model. The meandering shape of Shihmen
      Reservoir and its surrounding rivers caused a complex interplay between
      hydrological conditions and abiotic and biotic variables, resulting in
      phytoplankton abundance that could not be estimated using certain variables.
      Additional water quality and hydrological variables at surrounding rivers and
      monitoring plans should be executed a few days before and after reservoir
      operations and heavy storm, which would assist in developing site-specific
      preventive strategies to control phytoplankton abundance.

PMID- 27885617
TI  - Assessment of impacts of land use changes on surface water using L-THIA model
      (case study: Zayandehrud river basin).
AB  - Land use changes in a basin are the most important factors affecting its
      hydrology and water quality. A hydrological model is an effective tool in
      assessing the effects of land use change on surface water. In this study, the
      effects of land use changes in the Zayandehrud basin are estimated using long
      term hydrologic impact assessment model. This model is applicable using long-term
      data on climate, soil hydrological groups, and land use maps. The study covered
      three land uses across 18 years (from 1997 to 2015), and we used data on 30 years
      of precipitation (from 1985 to 2015) in the model. The results of modeling
      revealed that the average runoff volume increased from around 5,765,034 m3 in
      1997 to 8,894,525 m3 in 2015. The results also showed an increase in runoff
      depth. Land use changes over the study period showed an increase of residential
      areas, bare land, and agricultural lands and a decrease of pasture and forests.
      The results can be used to make decisions and monitor changes in land use to
      control the depth and volume of runoff. Using output maps helps in delimitation
      of the areas that have high runoff average and in implementation of the
      management plans for controlling the amount of runoff in these areas. Appropriate
      land use design can decrease impacts of land use changes including hydrologic
      effects.

PMID- 27885618
TI  - Pre-clinical quantitative imaging and mouse-specific dosimetry for 111In-labelled
      radiotracers.
AB  - BACKGROUND: Accurate quantification in molecular imaging is essential to improve
      the assessment of novel drugs and compare the radiobiological effects of
      therapeutic agents prior to in-human studies. The aim of this study was to
      investigate the challenges and feasibility of pre-clinical quantitative imaging
      and mouse-specific dosimetry of 111In-labelled radiotracers. Attenuation, scatter
      and partial volume effects were studied using phantom experiments, and an
      activity calibration curve was obtained for varying sphere sizes. Six SK-OV-3
      tumour bearing mice were injected with 111In-labelled HER2-targeting monoclonal
      antibodies (mAbs) (range 5.58-8.52 MBq). Sequential SPECT imaging up to 197 h
      post-injection was performed using the Albira SPECT/PET/CT pre-clinical scanner.
      Mice were culled for quantitative analysis of biodistribution studies. The tumour
      activity, mass and percentage of injected activity per gram of tissue (%IA/g)
      were calculated at the final scan time point and compared to the values
      determined from the biodistribution data. Delivered 111In-labelled mAbs tumour
      absorbed doses were calculated using mouse-specific convolution dosimetry, and
      absorbed doses for 90Y-labelled mAbs were extrapolated under the assumptions of
      equivalent injected activities, biological half-lives and uptake distributions as
      for 111In. RESULTS: For the sphere sizes investigated (volume 0.03-1.17 ml), the
      calibration factor varied by a factor of 3.7, whilst for the range of tumour
      masses in the mice (41-232 mg), the calibration factor changed by a factor of
      2.5. Comparisons between the mice imaging and the biodistribution results showed
      a statistically significant correlation for the tumour activity (r = 0.999, P <
      0.0001) and the tumour mass calculations (r = 0.977, P = 0.0008), whilst no
      correlation was found for the %IA/g (r = 0.521, P = 0.29). Median tumour-absorbed
      doses per injected activity of 52 cGy/MBq (range 36-69 cGy/MBq) and 649 cGy/MBq
      (range 441-950 cGy/MBq) were delivered by 111In-labelled mAbs and extrapolated
      for 90Y-labelled mAbs, respectively. CONCLUSIONS: This study demonstrates the
      need for multidisciplinary efforts to standardise imaging and dosimetry protocols
      in pre-clinical imaging. Accurate image quantification can improve the
      calculation of the activity, %IA/g and absorbed dose. Diagnostic imaging could be
      used to estimate the injected activities required for therapeutic studies,
      potentially reducing the number of animals used.

PMID- 27885619
TI  - The Crystal Structure of Micro- and Nanopowders of ZnS Studied by EPR of Mn2+ and
      XRD.
AB  - The crystal structure of micro- and nanopowders of ZnS doped with different
      impurities was analyzed by the electron paramagnetic resonance (EPR) of Mn2+ and
      XRD methods. The powders of ZnS:Cu, ZnS:Mn, ZnS:Co, and ZnS:Eu with the particle
      sizes of 5-7 MUm, 50-200 nm, 7-10 MUm, and 5-7 nm, respectively, were studied.
      Manganese was incorporated in the crystal lattice of all the samples as
      uncontrolled impurity or by doping. The Mn2+ ions were used as EPR structural
      probes. It is found that the ZnS:Cu has the cubic structure, the ZnS:Mn has the
      hexagonal structure with a rhombic distortion, the ZnS:Co is the mixture of the
      cubic and hexagonal phases in the ratio of 1:10, and the ZnS:Eu has the cubic
      structure and a distorted cubic structure with stacking defects in the ratio 3:1.
      The EPR technique is shown to be a powerful tool in the determination of the
      crystal structure for mixed-polytype ZnS powders and powders with small
      nanoparticles. It allows observation of the stacking defects, which is revealed
      in the XRD spectra.

PMID- 27885620
TI  - Removal of Metal Nanoparticles Colloidal Solutions by Water Plants.
AB  - The ability of seven species of aquatic plants (Elodea canadensis, Najas
      guadelupensis, Vallisneria spiralis L., Riccia fluitans L., Limnobium laevigatum,
      Pistia stratiotes L., and Salvinia natans L.) to absorb metal nanoparticles from
      colloidal solutions was studied. It was established that investigated aquatic
      plants have a high capacity for removal of metal nanoparticles from aqueous
      solution (30-100%) which indicates their high phytoremediation potential.
      Analysis of the water samples content for elements including the mixture of
      colloidal solutions of metal nanoparticles (Mn, Cu, Zn, Ag + Ag2O) before and
      after exposure to plants showed no significant differences when using submerged
      or free-floating hydrophytes so-called pleuston. However, it was found that the
      presence of submerged hydrophytes in aqueous medium (E. canadensis, N.
      guadelupensis, V. spiralis L., and R. fluitans L.) and significant changes in the
      content of photosynthetic pigments, unlike free-floating hydrophytes (L.
      laevigatum, P. stratiotes L., S. natans L.), had occur. Pleuston possesses higher
      potential for phytoremediation of contaminated water basins polluted by metal
      nanoparticles. In terms of removal of nanoparticles among studied free-floating
      hydrophytes, P. stratiotes L. and S. natans L. deserve on special attention.

PMID- 27885621
TI  - Reduction of Polarization Field Strength in Fully Strained c-Plane InGaN/(In)GaN
      Multiple Quantum Wells Grown by MOCVD.
AB  - The polarization fields in c-plane InGaN/(In)GaN multiple quantum well (MQW)
      structures grown on sapphire substrate by metal-organic chemical vapor deposition
      are investigated in this paper. The indium composition in the quantum wells
      varies from 14.8 to 26.5% for different samples. The photoluminescence
      wavelengths are calculated theoretically by fully considering the related effects
      and compared with the measured wavelengths. It is found that when the indium
      content is lower than 17.3%, the measured wavelengths agree well with the
      theoretical values. However, when the indium content is higher than 17.3%, the
      measured ones are much shorter than the calculation results. This discrepancy is
      attributed to the reduced polarization field in the MQWs. For the MQWs with lower
      indium content, 100% theoretical polarization can be maintained, while, when the
      indium content is higher, the polarization field decreases significantly. The
      polarization field can be weakened down to 23% of the theoretical value when the
      indium content is 26.5%. Strain relaxation is excluded as the origin of the
      polarization reduction because there is no sign of lattice relaxation in the
      structures, judging by the X-ray diffraction reciprocal space mapping. The
      possible causes of the polarization reduction are discussed.

PMID- 27885622
TI  - The Role of Air Adsorption in Inverted Ultrathin Black Phosphorus Field-Effect
      Transistors.
AB  - Few-layer black phosphorus (BP) attracts much attention owing to its high
      mobility and thickness-tunable band gap; however, compared with the commonly
      studied transition metal dichalcogenides (TMDCs), BP has the unfavorable property
      of degrading in ambient conditions. Here, we propose an inverted dual gates
      structure of ultrathin BP FET to research the air adsorption on BP. In
      fabrication process of back-gate BP FET, BP was transferred directly onto a wafer
      covered with electrodes. Thus, we can exclude the BP degradation during the
      process of electrodes fabrication, such as electron beam lithography (EBL) and
      thermal evaporation process. Furthermore, without any electrode covering BP, BP
      could be in full contact with the air; then the accurate effect of the air
      adsorption on BP can be researched in detail. The results clearly show that
      annealing can remove the p-doping resulted from the metastable oxygen adsorbed on
      the surface of BP, but the adsorption can be restored in a few hours exposure. In
      addition, both back and top gate inverted BP FETs exhibit a favorable
      performance. Therefore, this inverted structure is also an optional structure to
      reduce the influence of the instability of BP devices.

PMID- 27885623
TI  - Shape- and Size-Controlled Synthesis of Silver Nanoparticles Using Aloe vera
      Plant Extract and Their Antimicrobial Activity.
AB  - Biogenic synthesis of silver nanoparticles (AgNP) was performed at room
      temperature using Aloe vera plant extract in the presence of ammoniacal silver
      nitrate as a metal salt precursor. The formation of AgNP was monitored by UV
      visible spectroscopy at different time intervals. The shape and size of the
      synthesized particle were visualized by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM) observations. These results were confirmed
      by X-ray powder diffraction (XRD) and Fourier transform infrared spectroscopy
      (FTIR) analyses and further supported by surface-enhanced Raman
      spectroscopy/Raman scattering (SERS) study. UV-visible spectrum has shown a sharp
      peak at 420 nm and further evidenced by FTIR peak profile (at 1587.6, 1386.4, and
      1076 cm-1 with corresponding compounds). The main band position with SERS was
      noticed at 1594 cm-1 (C-C stretching vibration). When samples were heated under
      microwave radiation, AgNP with octahedron shapes with 5-50 nm were found and this
      method can be one of the easier ways to synthesis anisotropic AgNP, in which the
      plant extract plays a vital role to regulate the size and shape of the
      nanoparticles. Enhanced antibacterial effects (two- to fourfold) were observed in
      the case of Aloe vera plant protected AgNP than the routinely synthesized
      antibiotic drugs. Shape and size-controlled synthesis of silver nanoparticles
      using Aloe vera plant extract.

PMID- 27885624
TI  - Introduction to the Glutamate-Glutamine Cycle.
AB  - The term 'glutamate-glutamine cycle' was coined several decades ago based on the
      observation that using certain 14C-labeled precursors for studies of brain
      metabolism the specific radioactivity of glutamine generated from glutamate was
      higher than that of glutamate, its immediate precursor. This is metabolically
      impossible unless it is assumed that at least two distinct pools of these amino
      acids exist. This combined with the finding that the enzyme synthesizing
      glutamine from glutamate was expressed in astrocytes but not in neurons formed
      the basis of the notion that a cycle must exist in which glutamate released from
      neurons is transported into astrocytes, converted to glutamine which is
      subsequently returned to neurons and converted to glutamate by an enzyme the
      activity of which is much higher in neurons than in astrocytes. Originally this
      cycle was supposed to function in a stoichiometric fashion but more recent
      research has seriously questioned this.This volume of Advances in Neurobiology is
      intended to provide a detailed discussion of recent developments in research
      aimed at delineating the functional roles of the cycle taking into account that
      in order for this system to work there must be a tight coupling between
      metabolism of glutamate in astrocytes, transfer of glutamine to neurons and de
      novo synthesis of glutamine in astrocytes. To understand this, knowledge about
      the activity and regulation of the enzymes and transporters involved in these
      processes is required and as can be seen from the table of contents these issues
      will be dealt with in detail in the individual chapters of the book.

PMID- 27885625
TI  - Glucose, Lactate, beta-Hydroxybutyrate, Acetate, GABA, and Succinate as
      Substrates for Synthesis of Glutamate and GABA in the Glutamine-Glutamate/GABA
      Cycle.
AB  - The glutamine-glutamate/GABA cycle is an astrocytic-neuronal pathway transferring
      precursors for transmitter glutamate and GABA from astrocytes to neurons. In
      addition, the cycle carries released transmitter back to astrocytes, where a
      minor fraction (~25 %) is degraded (requiring a similar amount of resynthesis)
      and the remainder returned to the neurons for reuse. The flux in the cycle is
      intense, amounting to the same value as neuronal glucose utilization rate or 75
      80 % of total cortical glucose consumption. This glucose:glutamate ratio is
      reduced when high amounts of beta-hydroxybutyrate are present, but beta
      hydroxybutyrate can at most replace 60 % of glucose during awake brain function.
      The cycle is initiated by alpha-ketoglutarate production in astrocytes and its
      conversion via glutamate to glutamine which is released. A crucial reaction in
      the cycle is metabolism of glutamine after its accumulation in neurons. In
      glutamatergic neurons all generated glutamate enters the mitochondria and its
      exit to the cytosol occurs in a process resembling the malate-aspartate shuttle
      and therefore requiring concomitant pyruvate metabolism. In GABAergic neurons one
      half enters the mitochondria, whereas the other one half is released directly
      from the cytosol. A revised concept is proposed for the synthesis and metabolism
      of vesicular and nonvesicular GABA. It includes the well-established neuronal
      GABA reuptake, its metabolism, and use for resynthesis of vesicular GABA. In
      contrast, mitochondrial glutamate is by transamination to alpha-ketoglutarate and
      subsequent retransamination to releasable glutamate essential for the
      transaminations occurring during metabolism of accumulated GABA and subsequent
      resynthesis of vesicular GABA.

PMID- 27885626
TI  - Anaplerosis for Glutamate Synthesis in the Neonate and in Adulthood.
AB  - A central task of the tricarboxylic acid (TCA, Krebs, citric acid) cycle in brain
      is to provide precursors for biosynthesis of glutamate, GABA, aspartate and
      glutamine. Three of these amino acids are the partners in the intricate
      interaction between astrocytes and neurons and form the so-called glutamine
      glutamate (GABA) cycle. The ketoacids alpha-ketoglutarate and oxaloacetate are
      removed from the cycle for this process. When something is removed from the TCA
      cycle it must be replaced to permit the continued function of this essential
      pathway, a process termed anaplerosis. This anaplerotic process in the brain is
      mainly carried out by pyruvate carboxylation performed by pyruvate carboxylase.
      The present book chapter gives an introduction and overview into this
      carboxylation and additionally anaplerosis mediated by propionyl-CoA carboxylase
      under physiological conditions in the adult and in the developing rodent brain.
      Furthermore, examples are given about pathological conditions in which
      anaplerosis is disturbed.

PMID- 27885627
TI  - Enzyme Complexes Important for the Glutamate-Glutamine Cycle.
AB  - Transient multienzyme and/or multiprotein complexes (metabolons) direct
      substrates toward specific pathways and can significantly influence the
      metabolism of glutamate and glutamine in the brain. Glutamate is the primary
      excitatory neurotransmitter in brain. This neurotransmitter has essential roles
      in normal brain function including learning and memory. Metabolism of glutamate
      involves the coordinated activity of astrocytes and neurons and high affinity
      transporter proteins that are selectively distributed on these cells. This
      chapter describes known and possible metabolons that affect the metabolism of
      glutamate and related compounds in the brain, as well as some factors that can
      modulate the association and dissociation of such complexes, including protein
      modifications by acylation reactions (e.g., acetylation, palmitoylation,
      succinylation, SUMOylation, etc.) of specific residues. Development of strategies
      to modulate transient multienzyme and/or enzyme-protein interactions may
      represent a novel and promising therapeutic approach for treatment of diseases
      involving dysregulation of glutamate metabolism.

PMID- 27885629
TI  - Glutaminases.
AB  - Mammalian glutaminases catalyze the stoichiometric conversion of L-glutamine to L
      glutamate and ammonium ions. In brain, glutaminase is considered the prevailing
      pathway for synthesis of the neurotransmitter pool of glutamate. Besides
      neurotransmission, the products of glutaminase reaction also fulfill crucial
      roles in energy and metabolic homeostasis in mammalian brain. In the last years,
      new functional roles for brain glutaminases are being uncovered by using
      functional genomic and proteomic approaches. Glutaminases may act as
      multifunctional proteins able to perform different tasks: the discovery of
      multiple transcript variants in neurons and glial cells, novel extramitochondrial
      localizations, and isoform-specific proteininteracting partners strongly support
      possible moonlighting functions for these proteins. In this chapter, we present a
      critical account of essential works on brain glutaminase 80 years after its
      discovery. We will highlight the impact of recent findings and thoughts in the
      context of the glutamate/glutamine brain homeostasis.

PMID- 27885628
TI  - BCAA Metabolism and NH3 Homeostasis.
AB  - The branched chain amino acids (BCAA) are essential amino acids required not only
      for growth and development, but also as nutrient signals and as nitrogen donors
      to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and
      oxidative decarboxylation of the BCAAs are catalysed by the branched-chain
      aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the
      branched-chain alpha-keto acid dehydrogenase enzyme complex (BCKDC),
      respectively. These proteins show tissue, cell compartmentation, and protein
      protein interactions, which call for substrate shuttling or channelling and
      nitrogen transfer for oxidation to occur. Efficient regulation of these pathways
      is mediated through the redox environment and phosphorylation in response to
      dietary and hormonal stimuli. The wide distribution of these proteins allows for
      effective BCAA utilisation. We discuss how BCAT, BCKDC, and glutamate
      dehydrogenase operate in supramolecular complexes, allowing for efficient
      channelling of substrates. The role of BCAAs in brain metabolism is highlighted
      in rodent and human brain, where differential expression of BCATm indicates
      differences in nitrogen metabolism between species. Finally, we introduce a new
      role for BCAT, where a change in function is triggered by oxidation of its redox
      active switch. Our understanding of how BCAA metabolism and nitrogen transfer is
      regulated is important as many studies now point to BCAA metabolic dysregulation
      in metabolic and neurodegenerative conditions.

PMID- 27885630
TI  - Vesicular Glutamate Uptake.
AB  - Glutamate is an excitatory neurotransmitter widely used in the vertebrate central
      nervous systems. The synaptic transmission process is characterized by three
      steps: (1) presynaptic vesicular transmitter uptake, (2) presynaptic release, and
      (3) postsynaptic receptor activation. Presynaptic vesicular glutamate uptake
      plays an initial pivotal role in glutamate transmission by concentrating
      glutamate in the vesicular lumen prior to its release. This active glutamate
      transport harnesses energy derived from ATP hydrolysis, and intra- or
      extravesicular chloride, and is highly specific to glutamate. The uptake system
      consists of a vesicular glutamate transporter (VGLUT) and v-type proton-pump
      ATPase, which generates an electrochemical proton gradient, the driving force of
      the transport. The major source of ATP is likely to be supplied by glycolytic
      vesicle-bound enzymes, glyceraldehyde 3-phosphate dehydrogenase, and 3
      phosphoglycerate kinase, rather than by mitochondrial ATP synthase. The VGLUT
      substrate glutamate is proposed to be synthesized by vesicle-bound aspartate
      amino transferase from alpha-ketoglutarate, not directly from glutamine. VGLUT
      has three isoforms, and gaged by their distributions they perform different
      physiological functions. The mechanism and regulation of vesicular glutamate
      uptake are discussed. The pharmacology of vesicular glutamate uptake is a
      developing field of inquiry.

PMID- 27885631
TI  - The Glutamine Transporters and Their Role in the Glutamate/GABA-Glutamine Cycle.
AB  - Glutamine is a key amino acid in the CNS, playing an important role in the
      glutamate/GABA-glutamine cycle (GGC). In the GGC, glutamine is transferred from
      astrocytes to neurons, where it will replenish the inhibitory and excitatory
      neurotransmitter pools. Different transporters participate in this neural
      communication, i.e., the transporters responsible for glutamine efflux from
      astrocytes and influx into the neurons, such as the members of the SNAT, LAT,
      y+LAT, and ASC families of transporters. The SNAT family consists of the
      transporter isoforms SNAT3 and SNAT5 that are related to efflux from the
      astrocytic compartment, and SNAT1 and SNAT2 that are associated with glutamine
      uptake into the neuronal compartment. The isoforms SNAT7 and SNAT8 do not have
      their role completely understood, but they likely also participate in the GGC.
      The isoforms LAT2 and y+LAT2 facilitate the exchange of neutral amino acids and
      cationic amino acids (y+LAT2 isoform) and have been associated with glutamine
      efflux from astrocytes. ASCT2 is a Na+-dependent antiporter, the participation of
      which in the GGC also remains to be better characterized. All these isoforms are
      tightly regulated by transcriptional and translational mechanisms, which are
      induced by several determinants such as amino acid deprivation, hormones, pH, and
      the activity of different signaling pathways. Dysfunctional glutamine transporter
      activity has been associated with the pathophysiological mechanisms of certain
      neurologic diseases, such as Hepatic Encephalopathy and Manganism. However, there
      might also be other neuropathological conditions associated with an altered GGC,
      in which glutamine transporters are dysfunctional. Hence, it appears to be of
      critical importance that the physiological and pathological aspects of glutamine
      transporters are thoroughly investigated.

PMID- 27885632
TI  - Glutamine Metabolism in Gliomas.
AB  - By histological, morphological criteria, and malignancy, brain tumors are
      classified by WHO into grades I (most benign) to IV (highly malignant), and
      gliomas are the most frequently occurring class throughout the grades. Similar to
      peripheral tumors, the growth of glia-derived tumor cells largely depends on
      glutamine (Gln), which is vividly taken up by the cells, using mostly ASCT2 and
      SN1 as Gln carriers. Tumor growth-promoting effects of Gln are associated with
      its phosphate-activated glutaminase (GA) (specifically KGA)-mediated degradation
      to glutamate (Glu) and/or with its entry to the energy- and intermediate
      metabolite-generating pathways related to the tricarboxylic acid cycle. However,
      a subclass of liver-type GA are absent in glioma cells, a circumstance which
      allows phenotype manipulations upon their transfection to the cells. Gln-derived
      Glu plays a major role in promoting tumor proliferation and invasion. Glu is
      relatively inefficiently recycled to Gln and readily leaves the cells by exchange
      with the extracellular pool of the glutathione (GSH) precursor Cys mediated by xc
      transporter. This results in (a) cell invasion-fostering interaction of Glu with
      ionotropic Glu receptors in the surrounding tissue, (b) intracellular
      accumulation of GSH which increases tumor resistance to radio- and chemotherapy.

PMID- 27885633
TI  - Oligodendrocytes: Development, Physiology and Glucose Metabolism.
AB  - The glutamate-glutamine cycle is an outstanding example of how essential neuronal
      glial interactions are for brain function. For several decades, this and other
      metabolic cycles in the brain have only included neurons and astrocytes but not
      oligodendrocytes, the myelinating cells of the central nervous system (CNS).
      Recent data revealed that oligodendrocytes are highly metabolically active cells
      in the brain and, therefore, should not be ignored. Using 13C-labelled glucose in
      combination with nuclear magnetic resonance spectroscopy (MRS) and/or mass
      spectrometry (MS) it is possible to characterize metabolic functions in primary
      oligodendrocyte cultures. Mature rat oligodendrocytes avidly metabolize glucose
      in the cytosol and pyruvate derived from glucose in mitochondria. Moreover, they
      seem to have the ability of performing anaplerosis from pyruvate, which might
      enable them to synthesize metabolites de novo and transfer them to neighbouring
      cells. All these original findings highlight the importance of investigating
      oligodendrocyte metabolism separately from that of astrocytes and neurons to be
      able to discern the roles played by the individual partners. This is of
      particular importance in the white matter where the number of oligodendrocytes is
      considerable. The present book chapter provides some background on
      oligodendrocyte biology and physiology and summarizes the not very extensive
      information published on glucose metabolism in oligodendrocytes.

PMID- 27885634
TI  - Dysregulation of Glutamate Cycling Mediates Methylmercury-Induced Neurotoxicity.
AB  - To examine the toxicological implications of glutamate, this chapter will focus
      specifically on its impact in the brain. More explicitly, it will illustrate the
      role glutamate plays in mediating methylmercury (MeHg)-induced neurotoxicity. In
      this chapter, one intends to highlight the processes that occur prior to
      glutamate-stimulated excitotoxicity and subsequent neurodegeneration. As such, it
      will emphasize three main routes by which MeHg alters glutamate homeostasis. It
      is essential to recognize that these effects are not mutually exclusive, and that
      they synergistically influence glutamate dysregulation. Furthermore, the
      consequences of MeHg exposure will be presented here as a direct pathway;
      however, it must be noted these effects occur simultaneously. First, glutamate
      uptake will be reviewed emphasizing the function of astrocytes. Next, the
      induction of oxidative stress by MeHg exposure will be discussed. This process
      has a two-fold effect on glutamate homeostasis by (1) inhibiting extracellular
      glutamate uptake and (2) altering transcription of genes vital to glutamate
      cycling. Finally, the impact glutamate dysregulation has on glutathione synthesis
      will be examined. Although this chapter centers on the link between glutamate and
      MeHg toxicity, it is imperative that the reader acknowledges the processes
      discussed here can be extended to any pro-oxidant.

PMID- 27885635
TI  - Astroglia, Glutamatergic Transmission and Psychiatric Diseases.
AB  - Astrocytes are primary homeostatic cells of the central nervous system. They
      regulate glutamatergic transmission through the removal of glutamate from the
      extracellular space and by supplying neurons with glutamine. Glutamatergic
      transmission is generally believed to be significantly impaired in the contexts
      of all major neuropsychiatric diseases. In most of these neuropsychiatric
      diseases, astrocytes show signs of degeneration and atrophy, which is likely to
      be translated into reduced homeostatic capabilities. Astroglial glutamate
      uptake/release and glutamate homeostasis are affected in all forms of major
      psychiatric disorders and represent a common mechanism underlying
      neurotransmission disbalance, aberrant connectome and overall failure on
      information processing by neuronal networks, which underlie pathogenesis of
      neuropsychiatric diseases.

PMID- 27885636
TI  - Glutamine Synthetase: Role in Neurological Disorders.
AB  - Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that
      synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively
      located in astrocytes where it serves to maintain the glutamate-glutamine cycle,
      as well as nitrogen metabolism. Changes in the activity of GS, as well as its
      gene expression, along with excitotoxicity, have been identified in a number of
      neurological conditions. The literature describing alterations in the activation
      and gene expression of GS, as well as its involvement in different neurological
      disorders, however, is incomplete. This review summarizes changes in GS gene
      expression/activity and its potential contribution to the pathogenesis of several
      neurological disorders, including hepatic encephalopathy, ischemia, epilepsy,
      Alzheimer's disease, amyotrophic lateral sclerosis, traumatic brain injury,
      Parkinson's disease, and astroglial neoplasms. This review also explores the
      possibility of targeting GS in the therapy of these conditions.

PMID- 27885637
TI  - The Glutamate-Glutamine Cycle in Epilepsy.
AB  - Epilepsy is a complex, multifactorial disease characterized by spontaneous
      recurrent seizures and an increased incidence of comorbid conditions such as
      anxiety, depression, cognitive dysfunction, and sudden unexpected death. About 70
      million people worldwide are estimated to suffer from epilepsy, and up to one
      third of all people with epilepsy are expected to be refractory to current
      medications. Development of more effective and specific antiepileptic
      interventions is therefore requisite. Perturbations in the brain's glutamate
      glutamine cycle, such as increased extracellular levels of glutamate, loss of
      astroglial glutamine synthetase, and changes in glutaminase and glutamate
      dehydrogenase, are frequently encountered in patients with epilepsy. Hence,
      manipulations of discrete glutamate-glutamine cycle components may represent
      novel approaches to treat the disease. The goal of his review is to discuss some
      of the glutamate-glutamine cycle components that are altered in epilepsy,
      particularly neurotransmitters and metabolites, enzymes, amino acid transporters,
      and glutamate receptors. We will also review approaches that potentially could be
      used in humans to target the glutamate-glutamine cycle. Examples of such
      approaches are treatment with glutamate receptor blockers, glutamate scavenging,
      dietary intervention, and hypothermia.

PMID- 27885638
TI  - When will biomedical research enter the 21st century? A 'young' perspective.

PMID- 27885639
TI  - Cosmopolitanism and the relevance of 'zombie concepts': the case of anomic
      suicide amongst Alevi Kurd youth.
AB  - Against Beck's claims that conventional sociological concepts and categories are
      zombie categories, this paper argues that Durkheim's theoretical framework in
      which suicide is a symptom of an anomic state of society can help us understand
      the diversity of trajectories that transnational migrants follow and that shape
      their suicide rates within a cosmopolitan society. Drawing on ethnographic data
      collected on eight suicides and three attempted suicide cases of second
      generation male Alevi Kurdish migrants living in London, this article explains
      the impact of segmented assimilation/adaptation trajectories on the incidence of
      suicide and how their membership of a 'new rainbow underclass', as a
      manifestation of cosmopolitan society, is itself an anomic social position with a
      lack of integration and regulation.

PMID- 27885640
TI  - Differences in Topographical Pressure Pain Sensitivity Maps of the Scalp Between
      Patients With Migraine and Healthy Controls.
AB  - OBJECTIVE: To investigate differences in topographical pressure pain sensitivity
      maps of the scalp between patients with migraine and healthy controls considering
      the chronicity (episodic/chronic) and side (strictly unilateral/bilateral) of the
      symptoms. BACKGROUND: It seems that the trigeminal area is sensitized in
      migraine. No study has investigated topographical pressure sensitivity maps of
      the scalp in patients with migraine. METHODS: Pressure pain thresholds (PPTs)
      were assessed from 21 points distributed over the scalp in 86 patients with
      episodic migraine, 76 with chronic migraine, and 42 healthy age and matched
      healthy controls in a blinded design. Topographical pressure pain sensitivity
      maps based on interpolation of the PPTs were constructed. Clinical features of
      migraine, anxiety, and depression (Hospital Anxiety and Depression Scale, HADS)
      were collected. RESULTS: The multivariate ANCOVA revealed significant differences
      in PPT between points (F = 55.674; P < .001) and groups (F = 5.316; P = .006),
      but not sides (F = 0.880; P = .417). No significant effect of gender (F = 0.897;
      P = .656), depression (F = 1.109; P = .220), or anxiety (F = 0.981; F = 0.569)
      was found. Post hoc comparisons revealed: (1) lower PPTs in both migraine groups
      than in healthy controls in all points (P < .001); (2) no significant differences
      between chronic or episodic migraine (P > .335) except for Fp1 (P = .045) and Fp2
      (P = .017) points where subjects with chronic migraine had lower PPTs than those
      with episodic migraine; (3) no differences between bilateral/unilateral migraine
      (P > .417). An anterior to posterior gradient was found, with the lowest PPTs
      located in frontal regions and the highest PPTs in occipital areas (all groups, P
      < .001). CONCLUSIONS: We found that patients with migraine exhibited generalized
      pressure pain hypersensitivity in the head as compared to healthy controls and
      that hypersensitivity was similar between episodic/chronic and
      unilateral/bilateral migraine. Topographical pressure pain sensitivity maps
      revealed an anterior to posterior gradient of pressure pain sensitivity in both
      migraine and control groups.

PMID- 27885641
TI  - Apophyseal Ossification of the Iliac Crest in Forensic Age Estimation: Computed
      Tomography Standards for Modern Australian Subadults.
AB  - This study contrasts the ontogeny of the iliac crest apophysis using conventional
      radiography and multislice computed tomography (MSCT), providing probabilistic
      information for age estimation of modern Australian subadults. Retrospective
      abdominopelvic MSCT data acquired from 524 Australian individuals aged 7-25 and
      surveillance radiographs of adolescent idiopathic scoliosis patients included in
      the Paediatric Spine Research Group Progression Study (n = 531) were assessed.
      Ossification scoring of pseudo-radiographs and three-dimensional (3D) volume
      rendered reconstructions using Risser (1958) quantitative descriptors indicate
      discrepancies in age estimates, stage allocation, and conflicting morphological
      progression. To mitigate visualization limitations associated with two
      dimensional radiographs, we provide and validate a modified 3D-MSCT scoring tier
      of ossification, demonstrating complete fusion between 17.3-19.2 and 17.1-20.1
      years in males and females. Legal demarcation for doli incapax presumption and
      age of majority (18 years) can be achieved using probability estimates from a
      fitted cumulative probit model for apophyseal fusion using the recalibrated
      standards.

PMID- 27885650
TI  - Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease.
AB  - BACKGROUND: Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal
      antibodies that target the standard p40 subunit of the cytokines interleukin-12
      and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of
      Crohn's disease. OBJECTIVES: The objectives of this review were to assess the
      efficacy and safety of anti-IL-12/23p40 antibodies for induction of remission in
      Crohn's disease. SEARCH METHODS: We searched the following databases from
      inception to 12 September 2016: PubMed, MEDLINE, EMBASE, and the Cochrane Library
      (CENTRAL). References and conference abstracts were searched to identify
      additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs)
      trials in which monoclonal antibodies against IL-12/23p40 were compared to
      placebo or another active comparator in patients with active Crohn's disease were
      included.  DATA COLLECTION AND ANALYSIS: Two authors independently screened 
      studies for inclusion and extracted data. Methodological quality was assessed
      using the Cochrane risk of bias tool. The primary outcome was failure to induce
      clinical remission, defined as a Crohn's disease activity index (CDAI) of < 150
      points. Secondary outcomes included failure to induce clinical improvement,
      adverse events, serious adverse events, and withdrawals due to adverse events.
      Clinical improvement was defined as decreases of > 70 or > 100 points in the CDAI
      from baseline. We calculated the risk ratio (RR) and 95% confidence intervals
      (95% CI) for each outcome. Data were analyzed on an intention-to-treat basis. The
      overall quality of the evidence supporting the outcomes was evaluated using the
      GRADE criteria. MAIN RESULTS: Six RCTs (n = 2324 patients) met the inclusion
      criteria. A low risk of bias was assigned to all studies. The two briakinumab
      trials were not pooled due to differences in doses and time points for analysis.
      In both studies there was no statistically significant difference in remission
      rates. One study (n = 79) compared doses of 1 mg/kg and 3 mg/kg to placebo. In
      the briakinumab group 70% (44/63) of patients failed to enter clinical remission
      at 6 or 9 weeks compared to 81% (13/16) of placebo patients (RR 0.86, 95% CI 0.65
      to 1.14). Subgroup analysis revealed no significant differences by dose. The
      other briakinumab study (n = 230) compared intravenous doses of 200 mg, 400 mg
      and 700 mg with placebo. Eighty-four per cent (154/184) of briakinumab patients
      failed to enter clinical remission at six weeks compared to 91% (42/46) of
      placebo patients (RR 0.92, 95% CI 0.83 to 1.03). Subgroup analysis revealed no
      significant differences by dose. GRADE analyses of the briakinumab studies rated
      the overall quality of the evidence for the outcome clinical remission as low.
      Based on the results of these two studies the manufacturers of briakinumab
      stopped production of this medication. The ustekinumab studies were pooled
      despite differences in intravenous doses (i.e. 1mg/kg, 3 mg/kg, 4.5 mg/kg, and 6
      mg/kg), however the subcutaneous dose group was not included in the analysis, as
      it was unclear if subcutaneous was equivalent to intravenous dosing. There was a
      statistically significant difference in remission rates. At week six, 84%
      (764/914) of ustekinumab patients failed to enter remission compared to 90%
      (367/406) of placebo patients (RR 0.92, 95% CI 0.88 to 0.96; 3 studies; high
      quality evidence). Subgroup analysis showed a statistically significant
      difference for the 6.0 mg/kg dose group (moderate-quality evidence). There were
      statistically significant differences in clinical improvement between ustekinumab
      and placebo-treated patients. In the ustekinumab group, 55% (502/914) of patients
      failed to improve clinically (i.e. 70-point decline in CDAI score), compared to
      71% (287/406) of placebo patients (RR 0.78, 95% CI 0.71 to 0.85; 3 studies).
      Subgroup analysis revealed significant differences compared to placebo for the 1
      mg/kg, 4.5 mg/kg and 6 mg/kg dosage subgroups. Similarly for a 100-point decline
      in CDAI, 64% (588/914) of patients in the ustekinumab group failed to improve
      clinically compared to 78% (318/406) of placebo patients (RR 0.82, 95% CI 0.77 to
      0.88; 3 studies; high-quality evidence). Subgroup analysis showed a significant
      difference compared to placebo for the 4.5 mg/kg and 6.0 mg/kg (high-quality
      evidence) dose groups. There were no statistically significant differences in the
      incidence of adverse events, serious adverse events or withdrawal due to adverse
      events. Sixty-two per cent (860/1386) of ustekinumab patients developed at least
      one adverse event compared to 64% (407/637) of placebo patients (RR 0.97, 95% CI
      0.90 to 1.04; 4 studies; high-quality evidence). Five per cent (75/1386) of
      ustekinumab patients had a serious adverse event compared to 6% (41/637) of
      placebo patients (RR 0.83, 95% CI 0.58 to 1.20; 4 studies; moderate-quality
      evidence). The most common adverse events in briakinumab patients were injection
      site reactions and infections. Infections were the most common adverse event in
      ustekinumab patients. Worsening of Crohn's disease and serious infections were
      the most common serious adverse events. AUTHORS' CONCLUSIONS: High quality
      evidence suggests that ustekinumab is effective for induction of clinical
      remission and clinical improvement in patients with moderate to severe Crohn's
      disease. Moderate to high quality evidence suggests that the optimal dosage of
      ustekinumab is 6 mg/kg. Briakinumab and ustekinumab appear to be safe. Moderate
      quality evidence suggests no increased risk of serious adverse events. Future
      studies are required to determine the long-term efficacy and safety of
      ustekinumab in patients with moderate to severe Crohn's disease.

PMID- 27885651
TI  - Barossa Night: cohesion in the British Army officer corps.
AB  - Contrasting the classical explanation of military group cohesion as sustained by
      interpersonal bonds, recent scholars have highlighted the importance of
      ritualized communication, training and drills in explaining effective military
      performance in professional armies. While this has offered a welcome addition to
      the cohesion literature and a novel micro-sociological method of examining
      cohesion, its primary evidential base has been combat groups. Indeed, despite
      their prominent role in directing operations over the past decade, the British
      Army's officer corps has received relatively little attention from sociologists
      during this period. No attempt has been made to explain cohesion in the officer
      corps. Using a similar method to recent cohesion scholars, this paper seeks to
      address this imbalance by undertaking a micro-sociology of one ritual in
      particular: 'Barossa Night' in the Royal Irish Regiment. Firstly, it draws on the
      work of Durkheim to examine how cohesion amongst the officer corps is created and
      sustained through a dense array of practises during formal social rituals. It
      provides evidence that the use of rituals highlights that social solidarity is
      central to understanding officer cohesion. Secondly, following Hockey's work on
      how private soldiers negotiate order, the paper shows how this solidarity in the
      officer corps is based on a degree of negotiated order and the need to release
      organizational tensions inherent in a strictly hierarchical rank structure. It
      highlights how the awarding of gallantry medals can threaten this negotiated
      order and fuel deviancy. In examining this behaviour, the paper shows that even
      amongst an officer class traditionally viewed as the elite upholders of
      organizational discipline, the negotiation of rank and hierarchy can be fluid.
      How deviant behaviour is later accepted and normalized by senior officers
      indicates that negotiated order is as important to understanding cohesion in the
      British Army's officer corps as it is amongst private soldiers.

PMID- 27885652
TI  - Intercellular translocation of molecules via plasmodesmata in the multiseriate
      filamentous brown alga, Halopteris congesta (Sphacelariales, Phaeophyceae).
AB  - Despite the high number of studies on the fine structure of brown algal cells,
      only limited information is available on the intercelluar transportation of
      molecules via plasmodesmata in brown algae. In this study, plasmodesmatal
      permeability of Halopteris congesta was examined by observing the translocation
      of microinjected fluorescent tracers of different molecular sizes. The tip region
      of H. congesta consists of a cylindrical apical cell, while the basal region is
      multiseriate. Fluorescein isothiocyanate-dextran (FD; 3, 10, and 20 kDa) and
      recombinant green fluorescent protein (27 kDa) were injected into the apical cell
      and were observed to diffuse into the neighboring cells. FD of 40 kDa was
      detected only in the injected apical cell. The plasmodesmatal size exclusion
      limit was considered to be more than 20 kDa and less than 40 kDa. The extent of
      translocation of 3 and 10 kDa FD from the apical to neighboring cells 2 h
      postinjection was estimated based on the fluorescence intensity. It was suggested
      that the diffusing capacity of plasmodesmata varied according to molecular size.
      In order to examine acropetal and/or basipetal direction of molecular movement, 3
      and 10 kDa FD were injected into the third cell from the apical cell. Successive
      observations indicated that the diffusion of fluorescence in the acropetal
      direction took longer than that in the basipetal direction. No ultrastructural
      difference in plasmodesmata was noted among the cross walls.

PMID- 27885653
TI  - Comparing Standard and Selective Degradation DNA Extraction Methods: Results from
      a Field Experiment with Sexual Assault Kits<sup/>.
AB  - : A growing number of U.S. cities have large numbers of untested sexual assault
      kits (SAKs) in police property facilities. Testing older kits and maintaining
      current case work will be challenging for forensic laboratories, creating a need
      for more efficient testing methods. METHODS: We evaluated selective degradation
      methods for DNA extraction using actual case work from a sample of previously
      unsubmitted SAKs in Detroit, Michigan. We randomly assigned 350 kits to either
      standard or selective degradation testing methods and then compared DNA testing
      rates and CODIS entry rates between the two groups. RESULTS AND CONCLUSIONS:
      Continuation-ratio modeling showed no significant differences, indicating that
      the selective degradation method had no decrement in performance relative to
      customary methods. Follow-up equivalence tests indicated that CODIS entry rates
      for the two methods could differ by more than +/-5%. Selective degradation
      methods required less personnel time for testing and scientific review than
      standard testing.

PMID- 27885654
TI  - Historical Trends in Graduate Research and Training of Diplomates of the American
      Board of Forensic Anthropology.
AB  - The history of forensic anthropology has been documented by numerous scholars.
      These contributions have described the work of early pioneers in the field and
      have described important milestones, such as the founding of the Physical
      Anthropology Section of the American Academy of Forensic Sciences (AAFS) in 1972
      and the American Board of Forensic Anthropology (ABFA) in 1977. This paper
      contributes to the growing literature on the history of forensic anthropology by
      documenting the academic training of all individuals who have been granted
      diplomate status by the ABFA (n = 115). Doctoral dissertation titles were queried
      to discern broad patterns of research foci. A total of 39 doctoral granting
      institutions have trained diplomates and 77.3% of board-certified forensic
      anthropologists wrote dissertations involving skeletal biology, bioarchaeology,
      or forensic anthropology. Board-certified forensic anthropologists are a broadly
      trained group of professionals with far-reaching anthropological interests and
      expertise.

PMID- 27885655
TI  - A landscape-scale field experiment reveals the importance of dispersal in a
      resource-limited metacommunity.
AB  - Dispersal may play a strong role in driving species diversity across landscapes.
      Theoretically, dispersal permits species to remain extant within a metacommunity,
      even if they are periodically excluded from some local communities. Field tests
      of dispersal effects are difficult, and most non-experimental data suggest that
      environmental conditions play the predominant role in setting species diversity.
      However, most such studies cannot differentiate between patterns caused primarily
      by dispersal constraints vs. abiotic factors vs. biotic constraints (e.g.,
      priority effects). In 22 km of a sand-bed stream in southeastern Australia,
      strong longitudinal gradients in the abiotic environment and detritus densities
      (resources) mean that downstream locations have abiotic conditions that may be
      physiologically stressful, low resource densities and low species diversities. We
      experimentally increased the retention of detritus over 40 m stream lengths along
      the gradient, with other sites acting as controls. If dispersal is constrained,
      or abiotic or biotic factors primarily control community structure, then we
      predicted that increasing resources would result in no change in species
      composition. Alternatively, if dispersal is common, we predicted that species
      diversity would increase at treatment sites through colonization by species able
      to tolerate abiotic conditions downstream and able to invade established
      communities. Invertebrates were sampled prior to manipulation and then four times
      (1, 4, 9 and 12 months) following manipulation. Detrital standing stocks
      increased by an order of magnitude at treatment sites. Over 1 yr, invertebrate
      densities and species richness also increased in treatment sites. Effect sizes
      were strong in middle and downstream areas, which were colonized by upstream
      species. Thus, faunal composition of the downstream treatment sites became more
      similar to upstream locales, and beta-diversity across treatment sites declined
      as alpha-diversity increased. Out of 54 common taxa, roughly half responded to
      the experiment; responders and non-responders had similar proportions of upstream
      specialists and of different functional feeding groups. Contrary to many non
      experimental studies, our results demonstrate that extensive dispersal can be
      very important and, for many species, potentially more important than the abiotic
      environment or biotic constraints in affecting community structure when adequate
      resources are available.

PMID- 27885656
TI  - PHF6 mutations in paediatric acute myeloid leukaemia.

PMID- 27885659
TI  - Tribute to Reviewers.

PMID- 27885658
TI  - Early skin-to-skin contact for mothers and their healthy newborn infants.
AB  - BACKGROUND: Mother-infant separation post birth is common. In standard hospital
      care, newborn infants are held wrapped or dressed in their mother's arms, placed
      in open cribs or under radiant warmers. Skin-to-skin contact (SSC) begins ideally
      at birth and should last continually until the end of the first breastfeeding.
      SSC involves placing the dried, naked baby prone on the mother's bare chest,
      often covered with a warm blanket. According to mammalian neuroscience, the
      intimate contact inherent in this place (habitat) evokes neuro-behaviors ensuring
      fulfillment of basic biological needs. This time frame immediately post birth may
      represent a 'sensitive period' for programming future physiology and behavior.
      OBJECTIVES: To assess the effects of immediate or early SSC for healthy newborn
      infants compared to standard contact on establishment and maintenance of
      breastfeeding and infant physiology. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (17 December 2015), made
      personal contact with trialists, consulted the bibliography on kangaroo mother
      care (KMC) maintained by Dr Susan Ludington, and reviewed reference lists of
      retrieved studies. SELECTION CRITERIA: Randomized controlled trials that compared
      immediate or early SSC with usual hospital care. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed trials for inclusion and risk of bias,
      extracted data and checked them for accuracy. Quality of the evidence was
      assessed using the GRADE approach. MAIN RESULTS: We included 46 trials with 3850
      women and their infants; 38 trials with 3472 women and infants contributed data
      to our analyses. Trials took place in 21 countries, and most recruited small
      samples (just 12 trials randomized more than 100 women). Eight trials included
      women who had SSC after cesarean birth. All infants recruited to trials were
      healthy, and the majority were full term. Six trials studied late preterm infants
      (greater than 35 weeks' gestation). No included trial met all criteria for good
      quality with respect to methodology and reporting; no trial was successfully
      blinded, and all analyses were imprecise due to small sample size. Many analyses
      had statistical heterogeneity due to considerable differences between SSC and
      standard care control groups. Results for womenSSC women were more likely than
      women with standard contact to be breastfeeding at one to four months post birth,
      though there was some uncertainty in this estimate due to risks of bias in
      included trials (average risk ratio (RR) 1.24, 95% confidence interval (CI) 1.07
      to 1.43; participants = 887; studies = 14; I2 = 41%; GRADE: moderate quality).
      SSC women also breast fed their infants longer, though data were limited (mean
      difference (MD) 64 days, 95% CI 37.96 to 89.50; participants = 264; studies =
      six; GRADE:low quality); this result was from a sensitivity analysis excluding
      one trial contributing all of the heterogeneity in the primary analysis. SSC
      women were probably more likely to exclusively breast feed from hospital
      discharge to one month post birth and from six weeks to six months post birth,
      though both analyses had substantial heterogeneity (from discharge average RR
      1.30, 95% CI 1.12 to 1.49; participants = 711; studies = six; I2 = 44%; GRADE:
      moderate quality; from six weeks average RR 1.50, 95% CI 1.18 to 1.90;
      participants = 640; studies = seven; I2 = 62%; GRADE: moderate quality).Women in
      the SCC group had higher mean scores for breastfeeding effectiveness, with
      moderate heterogeneity (IBFAT (Infant Breastfeeding Assessment Tool) score MD
      2.28, 95% CI 1.41 to 3.15; participants = 384; studies = four; I2 = 41%). SSC
      infants were more likely to breast feed successfully during their first feed,
      with high heterogeneity (average RR 1.32, 95% CI 1.04 to 1.67; participants =
      575; studies = five; I2 = 85%). Results for infantsSSC infants had higher SCRIP
      (stability of the cardio-respiratory system) scores overall, suggesting better
      stabilization on three physiological parameters. However, there were few infants,
      and the clinical significance of the test was unclear because trialists reported
      averages of multiple time points (standardized mean difference (SMD) 1.24, 95% CI
      0.76 to 1.72; participants = 81; studies = two; GRADE low quality). SSC infants
      had higher blood glucose levels (MD 10.49, 95% CI 8.39 to 12.59; participants =
      144; studies = three; GRADE: low quality), but similar temperature to infants in
      standard care (MD 0.30 degree Celcius ( degrees C) 95% CI 0.13  degrees C to 0.47
      degrees C; participants = 558; studies = six; I2 = 88%; GRADE: low quality).
      Women and infants after cesarean birthWomen practicing SSC after cesarean birth
      were probably more likely to breast feed one to four months post birth and to
      breast feed successfully (IBFAT score), but analyses were based on just two
      trials and few women. Evidence was insufficient to determine whether SSC could
      improve breastfeeding at other times after cesarean. Single trials contributed to
      infant respiratory rate, maternal pain and maternal state anxiety with no power
      to detect group differences. SubgroupsWe found no differences for any outcome
      when we compared times of initiation (immediate less than 10 minutes post birth
      versus early 10 minutes or more post birth) or lengths of contact time (60
      minutes or less contact versus more than 60 minutes contact). AUTHORS'
      CONCLUSIONS: Evidence supports the use of SSC to promote breastfeeding. Studies
      with larger sample sizes are necessary to confirm physiological benefit for
      infants during transition to extra-uterine life and to establish possible dose
      response effects and optimal initiation time. Methodological quality of trials
      remains problematic, and small trials reporting different outcomes with different
      scales and limited data limit our confidence in the benefits of SSC for infants.
      Our review included only healthy infants, which limits the range of physiological
      parameters observed and makes their interpretation difficult.

PMID- 27885657
TI  - CDC25B is involved in the centrosomal microtubule nucleation in two-cell stage
      mouse embryos.
AB  - CDC25B has been demonstrated to activate the complex of CDK1/Cyclin B and trigger
      mitosis. We have recently demonstrated that p-CDC25B-Ser351 is located at the
      centrosomes of mouse oocytes and contributes to the release of mouse oocytes from
      prophase I arrest. But much less is known about CDC25B function at the centrosome
      in two-cell stage mouse embryos. Here we investigate the effect of CDC25B
      regulating the microtubules nucleation. Microinjection of anti-CDC25B antibody
      caused aberrant microtubule nucleation. In addition, embryos injected with anti
      CDC25B antibody showed the marked absence of microtubule repolymerization and
      Nek2 foci after nocodazole washout. CDC25B overexpression caused microtubule
      organizing center (MTOC) overduplication. Moreover, overexpression of CDC25B-?65
      mutant resulted in the loss of CDC25B localization in the perinuclear region and
      made CDC25B less efficient in inducing mitosis. We additionally identified that
      CDC25B is responsible for the pericentrin localization to the MTOC. Our data
      suggest an important role of CDC25B for microtubule nucleation and organization.
      N-terminal of CDC25B is required for regulating the microtubule dynamics and
      mitotic function.

PMID- 27885660
TI  - In-Transit Melanoma Metastasis Mimicking Nodular Fasciitis.

PMID- 27885661
TI  - Pyogenic granuloma association with isotretinoin treatment for acne.

PMID- 27885662
TI  - Hearing loss in association with topical imiquimod use for squamous cell
      carcinoma in situ (Bowen disease).

PMID- 27885663
TI  - Forensic Investigation of Cooperative Storage Cloud Service: Symform as a Case
      Study.
AB  - Researchers envisioned Storage as a Service (StaaS) as an effective solution to
      the distributed management of digital data. Cooperative storage cloud forensic is
      relatively new and is an under-explored area of research. Using Symform as a case
      study, we seek to determine the data remnants from the use of cooperative cloud
      storage services. In particular, we consider both mobile devices and personal
      computers running various popular operating systems, namely Windows 8.1, Mac OS X
      Mavericks 10.9.5, Ubuntu 14.04.1 LTS, iOS 7.1.2, and Android KitKat 4.4.4.
      Potential artefacts recovered during the research include data relating to the
      installation and uninstallation of the cloud applications, log-in to and log-out
      from Symform account using the client application, file synchronization as well
      as their time stamp information. This research contributes to an in-depth
      understanding of the types of terrestrial artifacts that are likely to remain
      after the use of cooperative storage cloud on client devices.

PMID- 27885665
TI  - Can Cephalometrics Discriminate Between the Sexes in a Diverse Juvenile Sample?
AB  - A critical component of the biological profile is sex estimation. Methods
      commonly used for sex estimation in adults do not work well for juveniles.
      Population-specific studies have used cephalometrics to estimate juvenile sex
      with 80-90% accuracy. Our study attempts to estimate sex in individuals less than
      18 years of age using a sample of 1618 lateral cephalograms incorporating all
      three Angle Class occlusions as well as population diversity. For the sample as a
      whole, 10 skeletal cephalometrics were found to have significant differences
      between the sexes. Males and females classify correctly about 50% of the time.
      Dividing the sample by age groups and race/ethnicity improves results for older
      age groups and Native Americans, Hispanics, and Asian Americans. Our results
      indicate that cephalometrics are not useful in determining sex of unidentified
      juveniles when age and race are not known.

PMID- 27885664
TI  - Haloperidol plus promethazine for psychosis-induced aggression.
AB  - BACKGROUND: Health services often manage agitated or violent people, and such
      behaviour is particularly prevalent in emergency psychiatric services (10%). The
      drugs used in such situations should ensure that the person becomes calm swiftly
      and safely. OBJECTIVES: To examine whether haloperidol plus promethazine is an
      effective treatment for psychosis-induced aggression. SEARCH METHODS: On 6 May
      2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is
      compiled by systematic searches of major resources (including MEDLINE, EMBASE,
      AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and
      their monthly updates, handsearches, grey literature, and conference proceedings.
      SELECTION CRITERIA: All randomised clinical trials with useable data focusing on
      haloperidol plus promethazine for psychosis-induced aggression. DATA COLLECTION
      AND ANALYSIS: We independently extracted data. For binary outcomes, we calculated
      risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat
      basis. For continuous data, we estimated the mean difference (MD) between groups
      and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk
      of bias for included studies and created 'Summary of findings' tables using
      GRADE. MAIN RESULTS: We found two new randomised controlled trials (RCTs) from
      the 2015 update searching. The review now includes six studies, randomising 1367
      participants and presenting data relevant to six comparisons.When haloperidol
      plus promethazine was compared with haloperidol alone for psychosis-induced
      aggression for the outcome not tranquil or asleep at 30 minutes, the combination
      treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87,
      high-quality evidence). There were 10 occurrences of acute dystonia in the
      haloperidol alone arm and none in the combination group. The trial was stopped
      early as haloperidol alone was considered to be too toxic.When haloperidol plus
      promethazine was compared with olanzapine, high-quality data showed both
      approaches to be tranquillising. It was suggested that the combination of
      haloperidol plus promethazine was more effective, but the difference between the
      two approaches did not reach conventional levels of statistical significance
      (n=300, 1 RCT, RR 0.60, 95% CI 0.22 to 1.61, high-quality evidence). Lower
      quality data suggested that the risk of unwanted excessive sedation was less with
      the combination approach (n=116, 2 RCTs, RR 0.67, 95% CI 0.12 to 3.84).When
      haloperidol plus promethazine was compared with ziprasidone all data were of
      lesser quality. We identified no binary data for the outcome tranquil or asleep.
      The average sedation score (Ramsay Sedation Scale) was lower for the combination
      approach but not to conventional levels of statistical significance (n=60, 1 RCT,
      MD -0.1, 95% CI - 0.58 to 0.38). These data were of low quality and it is unclear
      what they mean in clinical terms. The haloperidol plus promethazine combination
      appeared to cause less excessive sedation but again the difference did not reach
      conventional levels of statistical significance (n=111, 2 RCTs, RR 0.30, 95% CI
      0.06 to 1.43).We found few data for the comparison of haloperidol plus
      promethazine versus haloperidol plus midazolam. Average Ramsay Sedation Scale
      scores suggest the combination of haloperidol plus midazolam to be the most
      sedating (n=60, 1 RCT, MD - 0.6, 95% CI -1.13 to -0.07, low-quality evidence).
      The risk of excessive sedation was considerably less with haloperidol plus
      promethazine (n=117, 2 RCTs, RR 0.12, 95% CI 0.03 to 0.49, low-quality evidence).
      Haloperidol plus promethazine seemed to decrease the risk of needing restraints
      by around 12 hours (n=60, 1 RCT, RR 0.24, 95% CI 0.10 to 0.55, low-quality
      evidence). It may be that use of midazolam with haloperidol sedates swiftly, but
      this effect does not last long.When haloperidol plus promethazine was compared
      with lorazepam, haloperidol plus promethazine seemed to more effectively cause
      sedation or tranquillisation by 30 minutes (n=200, 1 RCT, RR 0.26, 95% CI 0.10 to
      0.68, high-quality evidence). The secondary outcome of needing restraints or
      seclusion by 12 hours was not clearly different between groups, with about 10% in
      each group needing this intrusive intervention (moderate-quality evidence).
      Sedation data were not reported, however, the combination group did have less
      'any serious adverse event' in 24-hour follow-up, but there were not clear
      differences between the groups and we are unsure exactly what the adverse effect
      was. There were no deaths.When haloperidol plus promethazine was compared with
      midazolam, there was clear evidence that midazolam is more swiftly tranquillising
      of an aggressive situation than haloperidol plus promethazine (n=301, 1 RCT, RR
      2.90, 95% CI 1.75 to 4.8, high-quality evidence). On its own, midazolam seems to
      be swift and effective in tranquillising people who are aggressive due to
      psychosis. There was no difference in risk of serious adverse event overall
      (n=301, 1 RCT, RR 1.01, 95% CI 0.06 to 15.95, high-quality evidence). However, 1
      in 150 participants allocated haloperidol plus promethazine had a swiftly
      reversed seizure, and 1 in 151 given midazolam had swiftly reversed respiratory
      arrest. AUTHORS' CONCLUSIONS: Haloperidol plus promethazine is effective and
      safe, and its use is based on good evidence. Benzodiazepines work, with midazolam
      being particularly swift, but both midazolam and lorazepam cause respiratory
      depression. Olanzapine intramuscular and ziprasidone intramuscular do seem to be
      viable options and their action is swift, but resumption of aggression with
      subsequent need to re-inject was more likely than with haloperidol plus
      promethazine. Haloperidol used on its own without something to offset its
      frequent and serious adverse effects does seem difficult to justify.

PMID- 27885666
TI  - Differential expression of foxl2 and cyp19a1a mRNA during gonad developmental
      stages in great sturgeon Huso huso.
AB  - This study aimed to determine the sex specificity and expression pattern of foxl2
      and cyp19a1a genes in great sturgeon Huso huso gonads during gonadal sex
      differentiation and development. The results revealed that foxl2 and cyp19a1a
      mainly expressed in female gonads and during gonad development the foxl2 and
      cyp19a1a mRNA expression is required for ovarian development.

PMID- 27885667
TI  - Validation of photo-identification as a mark-recapture method in the spotted
      eagle ray Aetobatus narinari.
AB  - The spotted eagle ray Aetobatus narinari is characterized by pigmentation
      patterns that are retained for up to 3.5 years. These pigmentations can be used
      to identify individuals through photo-identification. Only one study has
      validated this technique, but no study has estimated the percentage of correct
      identification of the rays using this technique. In order to carry out
      demographic research, a reliable photographic identification technique is needed.
      To achieve this validation for A. narinari, a double-mark system was established
      over 11 months and photographs of the dorsal surface of 191 rays were taken.
      Three body parts with distinctive natural patterns were analysed (dorsal surface
      of the cephalic region, dorsal surface of the pectoral fins and dorsal surface of
      the pelvic fins) in order to determine the body part that could be used to give
      the highest percentage of correct identification. The dorsal surface of the
      pectoral fins of A. narinari provides the most accurate photo-identification to
      distinguish individuals (88.2%).

PMID- 27885668
TI  - Characterization of Gambierdiscus lapillus sp. nov. (Gonyaulacales, Dinophyceae):
      a new toxic dinoflagellate from the Great Barrier Reef (Australia).
AB  - Gambierdiscus is a genus of benthic dinoflagellates found worldwide. Some species
      produce neurotoxins (maitotoxins and ciguatoxins) that bioaccumulate and cause
      ciguatera fish poisoning (CFP), a potentially fatal food-borne illness that is
      common worldwide in tropical regions. The investigation of toxigenic species of
      Gambierdiscus in CFP endemic regions in Australia is necessary as a first step to
      determine which species of Gambierdiscus are related to CFP cases occurring in
      this region. In this study, we characterized five strains of Gambierdiscus
      collected from Heron Island, Australia, a region in which ciguatera is endemic.
      Clonal cultures were assessed using (i) light microscopy; (ii) scanning electron
      microscopy; (iii) DNA sequencing based on the nuclear encoded ribosomal 18S and
      D8-D10 28S regions; (iv) toxicity via mouse bioassay; and (v) toxin profile as
      determined by Liquid Chromatography-Mass Spectrometry. Both the morphological and
      phylogenetic data indicated that these strains represent a new species of
      Gambierdiscus, G. lapillus sp. nov. (plate formula Po, 3', 0a, 7", 6c, 7-8s,
      5''', 0p, 2"" and distinctive by size and hatchet-shaped 2' plate). Culture
      extracts were found to be toxic using the mouse bioassay. Using chemical
      analysis, it was determined that they did not contain maitotoxin (MTX1) or known
      algal-derived ciguatoxin analogs (CTX3B, 3C, CTX4A, 4B), but that they contained
      putative MTX3, and likely other unknown compounds.

PMID- 27885669
TI  - Occult Adrenocortical Carcinoma and Unexpected Early Childhood Death.
AB  - A four-year-old previously well boy collapsed unexpectedly and was taken
      immediately to hospital, where he developed seizures and cardiogenic shock with
      lethal, rapidly progressing multi-organ failure. At autopsy, the height was >90th
      percentile and there were indications of early virilization. Internally, a
      friable tumor of the left adrenal gland was identified that had invaded the left
      renal vein and inferior vena cava. Histology revealed typical features of an
      adrenocortical carcinoma with aggregated trabeculae of cells containing abundant
      eosinophilic cytoplasm and large pleomorphic nuclei. There was strong positive
      cytoplasmic staining for inhibin; mitochondria were shown on electron microscopy
      to contain prominent electron-dense granules. Death was due to massive pulmonary
      tumor embolism. Although adrenocortical carcinomas are very rare and are more
      commonly found in adults, the current case demonstrates that they may also occur
      in childhood and be responsible for unexpected death by the very unusual
      mechanism of tumor embolism.

PMID- 27885670
TI  - Telomeric localization of the Arabidopsis-type heptamer repeat, (TTTAGGG)n , at
      the chromosome ends in Saccharina japonica (Phaeophyta).
AB  - Telomeres generally consist of short repeats of minisatellite DNA sequences and
      are useful in chromosome identification and karyotype analysis. To date,
      telomeres have not been characterized in the economically important brown seaweed
      Saccharina japonica, thus its full cytogenetic research and genetic breeding
      potential has not been realized. Herein, the tentative sequence of telomeres in
      S. japonica was identified by PCR amplification with primers designed based on
      the Arabidopsis-type telomere sequence (TTTAGGG)n , which was chosen out of three
      possible telomeric repeat DNA sequences typically present in plants and algae.
      After PCR optimization and cloning, sequence analysis of the amplified products
      from S. japonica genomic DNA showed that they were composed of repeat units,
      (TTTAGGG)n , in which the repeat number ranged from 15 to 63 (n = 46). This type
      of repeat sequence was verified by a Southern blot assay with the Arabidopsis
      type telomere sequence as a probe. The digestion of S. japonica genomic DNA with
      the exonuclease Bal31 illustrated that the target sequence corresponding to the
      Arabidopsis-type telomere sequence was susceptible to Bal31 digestion, suggesting
      that the repeat sequence was likely located at the outermost ends of the kelp
      chromosomes. Fluorescence in situ hybridizations with the aforementioned probe
      provided the initial cytogenetic evidence that the hybridization signals were
      principally localized at both ends of S. japonica chromosomes. This study
      indicates that the telomeric repeat of the kelp chromosomes is (TTTAGGG)n which
      differs from the previously reported (TTAGGG)n sequence in Ectocarpus siliculosus
      through genome sequencing, thereby suggesting distinct telomeres in brown
      seaweeds.

PMID- 27885672
TI  - Defining oral health: a new comprehensive definition.

PMID- 27885671
TI  - Recruited monocytic myeloid-derived suppressor cells promote the arrest of tumor
      cells in the premetastatic niche through an IL-1beta-mediated increase in E
      selectin expression.
AB  - The tumor premetastatic niche initiated by primary tumors is constructed by
      multiple molecular factors and cellular components and provides permissive
      condition that allows circulating tumor cells to successfully metastasize.
      Myeloid-derived suppressor cells (MDSCs), a population of immature cells in
      pathological conditions, play a critical role in the formation of the
      premetastatic niche. However, few researches are focused on the function of
      monocytic MDSCs (mo-MDSCs), a subtype of MDSCs, in the construction of the niche.
      Here, we show that the number of mo-MDSCs is significantly increased in the
      premetastatic lungs of tumor-bearing mice, thus promoting tumor cell arrest and
      metastasis. Before the arrival of tumor cells, the lung-recruited mo-MDSCs
      produced IL-1beta, thereby increasing E-selectin expression and promoting tumor
      cell arrest on endothelial cells. Depletion of mo-MDSCs in the premetastatic
      lungs decreased IL-1beta production, resulting in reduced E-selectin expression.
      In addition, compared with alveolar macrophages and interstitial macrophages, mo
      MDSCs were the major source of IL-1beta expression in the premetastatic lungs.
      Cytokine array analyses and transwell experiments revealed that CCL12 recruits mo
      MDSCs to premetastatic lungs. CCL12 knockdown in tumor-bearing mice significantly
      decreased mo-MDSC infiltration into the premetastatic lungs, leading to reduced E
      selectin expression. Overall, the permissive conditions produced by the
      infiltrated mo-MDSCs correlated with increased tumor cell arrest and metastasis.
      These results reveal a novel role of mo-MDSCs in constructing the premetastatic
      niche. Thus, inhibition of mo-MDSCs infiltration may change the premetastatic
      niche to normal condition and attenuate tumor metastasis.

PMID- 27885673
TI  - A new definition for oral health developed by the FDI World Dental Federation
      opens the door to a universal definition of oral health.

PMID- 27885674
TI  - Gender Differences in the Use of Complementary and Alternative Medicine and Their
      Association With Moderate Mental Distress in U.S. Adults With Migraines/Severe
      Headaches.
AB  - OBJECTIVE: We examined whether the prevalence of complementary and alternative
      medicine (CAM) use varies by gender, and assessed the interaction of gender and
      CAM use on moderate mental distress (MMD) in U.S. adults with migraines/severe
      headaches. METHODS: We used data from the 2012 National Health Interview Survey,
      which represents non-institutionalized U.S. adults with migraines/severe
      headaches (n = 4645 unweighted). Using a cross-sectional design with survey
      sampling techniques, we conducted descriptive analyses for prevalence of CAM use
      by gender. Multivariate logistic regression analyses were run to investigate
      potential roles of migraines/severe headaches and CAM use on MMD by gender.
      RESULTS: The overall prevalence of past year CAM use was 44.4%. Women
      consistently used CAM more frequently than men (P = .004). The most commonly used
      CAM types included herbal supplements (22.2%), massage (14.2%), and
      chiropractic/osteopathic (13.9%). After controlling for covariates, the odds of
      MDD were increased by the presence of migraines/severe headaches (P < .001) and
      the use of any CAM (P < .001). The interaction effect of migraines/severe
      headaches and CAM use decreased the odds of MMD by 27% in women (P < .05), but
      not in men. CONCLUSION: Women used CAM more frequently than men among adults with
      migraines/severe headaches in the United States. In addition, the interaction of
      gender and CAM use exists; the CAM use was associated with decreased odds of MMD
      among women only, suggesting that women with migraines/severe headaches may have
      benefited from CAM for their mental distress. Future research is needed to
      explore why such patterns vary by gender.

PMID- 27885675
TI  - Intratissue lymphovenous communications in the mechanism of action of
      vascularized lymph node transfer.
AB  - BACKGROUND AND OBJECTIVES: Vascularized lymph node transfer (VLNT) as a surgical
      treatment for cancer-related lymphedema has shown beneficial effects. The
      mechanism of action of this procedure involves lymphangiogenesis and lymphovenous
      communications (LVC) within the lymph nodes. We propose intratissue LVC as an
      additional element responsible for drainage of lymph to blood in the flap and
      examine this hypothesis in the current study. METHODS: This prospective study
      determined the passage of lymph to the venous system via intratissue LVC in 26
      free flaps used for breast reconstruction. We evaluated whether fluorescence was
      positive in the pedicle vein after increasing time intervals following
      intradermal injection of indocyanine green (ICG) dye into the flaps using near
      infra-red fluorescence lymphography. RESULTS: We studied 26 free flaps, 22 deep
      inferior epigastric perforator (DIEP) flaps (84.6%), and 4 superior gluteal
      artery perforator (SGAP) flaps (15.4%). Fluorescence in the pedicle vein was
      positive in 22 of the 26 flaps (P = 0.000). The median time for fluorescence
      evaluation in the pedicle vein was 120 min. CONCLUSIONS: Fluorescence in the
      pedicle vein after ICG intradermal injection indicates functional intratissue LVC
      in free flaps. J. Surg. Oncol. 2017;115:27-31. (c) 2016 Wiley Periodicals, Inc.

PMID- 27885677
TI  - Chemical composition of microalgae Heterochlorella luteoviridis and Dunaliella
      tertiolecta with emphasis on carotenoids.
AB  - BACKGROUND: Microalgae have been used as food supplements owing to their high
      protein, polyunsaturated fatty acid and carotenoid contents. As different
      carotenoids have distinct properties and the carotenoid composition of microalgae
      has been poorly explored in the literature, this study determined the complete
      carotenoid composition of two microalgae species, Heterochlorella luteoviridis
      and Dunaliella tertiolecta, using high-performance liquid chromatography coupled
      with diode array detection and tandem mass spectrometry (HPLC-DAD/MS2 ).
      Additionally, the proximate composition and major minerals were evaluated.
      RESULTS: The carotenoid composition of the two microalgae was similar, with 13
      carotenoids being found in H. luteoviridis and 12 in D. tertiolecta. The major
      carotenoids were all-trans-lutein (1.18 mg g-1 in H. luteoviridis and 1.59 mg g-1
      in D. tertiolecta), all-trans-violaxanthin (0.52 mg g-1 in H. luteoviridis and
      0.45 mg g-1 in D. tertiolecta) and all-trans-beta-carotene (0.50 mg g-1 in H.
      luteoviridis and 0.62 mg g-1 in D. tertiolecta). All-trans-lutein was the
      predominant carotenoid in both microalgae, representing around 40% (mass
      fraction) of the total carotenoids. The lutein content found in these microalgae
      was significantly higher (2-40 times) than that in other important food sources
      of lutein (e.g. parsley, carrot, red pepper and broccoli). CONCLUSION: The
      microalgae H. luteoviridis and D. tertiolecta are excellent sources of lutein
      that could be commercially exploited by the food and pharmaceutical industries.
      Moreover, it was confirmed that both microalgae are good sources of protein,
      lipids and calcium. (c) 2016 Society of Chemical Industry.

PMID- 27885676
TI  - Effect of deamidation-induced modification on umami and bitter taste of wheat
      gluten hydrolysates.
AB  - BACKGROUND: Bitter taste is the main limiting factor for various applications of
      protein hydrolysates. Frequently used physicochemical methods for debittering
      protein hydrolysates come with some undesired side effects. Deamidation-induced
      modification would be a very promising technique to improve the flavor of wheat
      gluten hydrolysates (WGHs). This study was designed to determine the effect of
      deamidation with certain enzymes or acid treatment on the chemical composition,
      bitterness and umami properties of WGHs. The difference between umami peptide and
      free glutamic acid on the suppression of bitterness is emphatically discussed.
      The optimal scheme is proposed based on the flavor of WGHs and the yield of
      peptides. RESULTS: The generation of umami substances suppressed bitter signal
      transduction. When the content of umami substances was relatively high, the umami
      enhancing properties of umami peptides were obviously effective. The intensity of
      umami taste was high enough to further suppress bitter taste in the course of
      neurocognitive functioning. CONCLUSION: When WGHs were treated with Glutaminase
      for 180 min, the umami taste score increased from 1.62 to 4.27 and the bitter
      taste score decreased from 1.33 to 0.65. (c) 2016 Society of Chemical Industry.

PMID- 27885678
TI  - What happens when N = 1 and you want plus 1?
AB  - We present a personal case study of what happens when a family has a child with
      an undiagnosed genetic disorder yet wishes to have more children free of the
      disease. After an intractable diagnostic odyssey for our oldest son, our family
      turned to exome sequencing. Exome sequencing found likely pathogenic variants of
      uncertain significance in the gene NGLY1. We used social media to uncover more
      cases for the newly discovered disorder and confirm the diagnosis in the process.
      With a diagnosis, we then explored and experienced a broad range of options for
      conceiving a child free of the disorder. Our success in having another child free
      of the disorder created a pathway for other families in our newly discovered
      disease community to do the same. (c) 2016 John Wiley & Sons, Ltd.

PMID- 27885680
TI  - Effect of high hydrostatic pressure on the enzymatic hydrolysis of bovine serum
      albumin.
AB  - BACKGROUND: The extent of enzymatic proteolysis mainly depends on accessibility
      of the peptide bonds, which stabilize the protein structure. The high hydrostatic
      pressure (HHP) process is able to induce, at certain operating conditions,
      protein displacement, thus suggesting that this technology can be used to modify
      protein resistance to the enzymatic attack. This work aims at investigating the
      mechanism of enzymatic hydrolysis assisted by HHP performed under different
      processing conditions (pressure level, treatment time). Bovine serum albumin was
      selected for the experiments, solubilized in sodium phosphate buffer (25 mg mL-1
      , pH 7.5) with alpha-chymotrypsin or trypsin (E/S ratio = 1/10) and HPP treatment
      (100-500 MPa, 15-25 min). RESULTS: HHP treatment enhanced the extent of the
      hydrolysis reaction of globular proteins, being more effective than conventional
      hydrolysis. At HHP treatment conditions maximizing the protein unfolding, the
      hydrolysis degree of proteins was increased as a consequence of the increased
      exposure of peptide bonds to the attack of proteolytic enzymes. The maximum
      hydrolysis degree (10% and 7% respectively for the samples hydrolyzed with alpha
      chymotrypsin and trypsin) was observed for the samples processed at 400 MPa for
      25 min. At pressure levels higher than 400 MPa the formation of aggregates was
      likely to occur; thus the degree of hydrolysis decreased. CONCLUSION: Protein
      unfolding represents the key factor controlling the efficiency of HHP-assisted
      hydrolysis treatments. The peptide produced under high pressure showed lower
      dimensions and a different structure with respect to those of the hydrolysates
      obtained when the hydrolysis was carried out at atmospheric pressure, thus
      opening new frontiers of application in food science and nutrition. (c) 2016
      Society of Chemical Industry.

PMID- 27885679
TI  - Clinical auditing as an instrument for quality improvement in breast cancer care
      in the Netherlands: The national NABON Breast Cancer Audit.
AB  - BACKGROUND: In 2011, the NABON Breast Cancer Audit (NBCA) was instituted as a
      nation-wide audit to address quality of breast cancer care and guideline
      adherence in the Netherlands. The development of the NBCA and the results of 4
      years of auditing are described. METHODS: Clinical and pathological
      characteristics of patients diagnosed with invasive breast cancer or in situ
      carcinoma (DCIS) and information regarding diagnosis and treatment are collected
      in all hospitals (n = 92) in the Netherlands. Thirty-two quality indicators
      measuring care structure, processes and outcomes were evaluated over time and
      compared between hospitals. RESULTS: The NBCA contains data of 56,927 patients
      (7,649 DCIS and 49,073 invasive cancers). Patients being discussed in pre- and
      post-operative multidisciplinary team meetings improved (2011: 83% and 91%; 2014:
      98% and 99%, respectively) over the years. Tumour margin positivity rates after
      breast-conserving surgery for invasive cancer requiring re-operation were
      consistently low (~5%). Other indicators, for example, the use of an MRI-scan
      prior to surgery or immediate breast reconstruction following mastectomy showed
      considerable hospital variation. CONCLUSIONS: Results shown an overall high
      quality of breast cancer care in all hospitals in the Netherlands. For most
      quality indicators improvement was seen over time, while some indicators showed
      yet unexplained variation. J. Surg. Oncol. 2017;115:243-249. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27885681
TI  - Dynamics of occurrence of refractory coeliac disease and associated complications
      over 25 years.
AB  - BACKGROUND: Refractory coeliac disease, enteropathy associated T-cell lymphoma
      and small bowel adenocarcinoma are rare but prognostically important
      complications in coeliac disease. AIM: To analyse potential changes in occurrence
      of complicated coeliac disease over the last 25 years. METHODS: One thousand one
      hundred and thirty eight patients were included and evaluated based on their time
      of first presentation at the Medical University of Vienna, Austria. Occurrences
      of refractory coeliac disease and associated malignancies were evaluated for 5
      year intervals from January 1990 until December 2014 and were compared over time.
      RESULTS: 2.6% (n = 29) were diagnosed with refractory coeliac disease (females
      65.6%, mean age at diagnosis 62.8 years). The proportion of those patients was
      2.6%, 3.1%, 3.3%, 2.7% and 0.5% for the 5 year intervals from 1990 onwards. Thus,
      the number of refractory cases has been decreasing since 2000 (P = 0.024). The
      number of patients presenting with lymphoma (n = 7) was 0.6%, 0.4%, 1.1%, 0.8%
      and 0% from 1990 to 2014. Similarly the number of patients with adenocarcinoma (n
      = 4) decreased to 0% until 2014. Overall mortality in patients suffering from
      refractory disease was 48%. Of all patients diagnosed with lymphoma 71.4% died
      with a 5-year survival rate of 28.6%. CONCLUSIONS: Over the past 15 years the
      occurrence of complicated coeliac disease has been decreasing. This possibly
      reflects a higher awareness of coeliac disease and optimised diagnosis and
      treatment with avoidance of long-term immunological disease activity. Symptomatic
      disease and a delay in diagnosis are risk factors for refractory coeliac disease
      and related cancer.

PMID- 27885682
TI  - Fractional laser-assisted drug uptake: Impact of time-related topical application
      to achieve enhanced delivery.
AB  - BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) is acknowledged to
      increase uptake of topically applied agents in skin. AFXL channels gradually
      close over time, which may impair this capability. The time frame for applying a
      drug after AFXL exposure remains to be established. The aim of this study, was to
      investigate the importance of time-related topical application after AFXL
      exposure and to relate resultant uptake in skin with AFXL channel morphology and
      skin integrity. STUDY DESIGN/MATERIALS AND METHODS: Buttock skin of healthy
      volunteers (n = 11) was exposed to 10,600 nm fractional CO2 laser using 5%
      density, 120 MUm beam diameter, 15 mJ pulse energy. Sodium fluorescein (NaF) a
      small, hydrophilic molecule (370 MW, log P =  -1.52) was applied under
      standardized conditions at specific time points after laser exposure (0, 2, 5,
      10, 30, 60, 90 minute, 6, 24, and 48 hours). Fluorescence photography collected
      fluorescence images up to 180 minute after NaF application. Optical coherence
      tomography (OCT) assessed AFXL channel dimensions and transepidermal water loss
      (TEWL) estimated loss of skin integrity. RESULTS: Fluorescence intensities (FI)
      were significantly elevated when NaF was applied up to 6 hours after laser
      exposure compared to non-laser-processed skin (median FI 1947 arbitrary units
      [interquartile range 1,246-3,560] versus 1,004 [350-1,538], P < 0.02). The
      highest FI occurred when NaF was applied within 30 minute after laser exposure
      and similar FI were reached for applications at 0, 2, 5, 10, and 30 minute after
      AFXL exposure (0 minute: 3,866 [3,526-4,575], 30 minute: 3,775 AU [3,070-4,484],
      P > 0.1). NaF application later than 30 minute after AFXL exposure resulted in
      gradually decreasing FI, becoming similar to intact skin when applied at 24-48
      hours after AFXL exposure (P > 0.2). OCT images demonstrated that AFXL channels
      closed over time (100% [100-100%] open up to 30 minute, 75% [4-86%] at 6 hours
      and 3% [0-15%] at 24-48 hours after AFXL exposure). TEWL measurements proved loss
      of skin integrity up to 6 hours after AFXL exposure, while integrity was similar
      in laser-exposed and non-laser-exposed skin at 24-48 hours. CONCLUSIONS: The time
      frame to maintain enhanced drug delivery sustained for several hours after AFXL
      exposure, corresponding to channel morphology and loss of skin integrity. Lasers
      Surg. Med. 49:348-354, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27885683
TI  - The effect of pH and amino acids on the formation of methylglyoxal in a glucose
      amino acid model system.
AB  - BACKGROUND: Methylglyoxal (MGO) as a alpha-dicarbonyl compound not only affects
      food flavor and color but also contributes to the loss of nutrition and the
      generation of toxic compounds. The study was carried out using a glucose-amino
      acid model system with incubation at 120  degrees C to investigate the effect of
      amino acids and pH on the formation of MGO. MGO derivative (2-methylquinoxaline)
      was detected by high-performance liquid chromatography with a diode array
      detector. Changes in glucose, amino acids and products such as acetic acid were
      tested using high-performance anion exchange chromatography with an
      electrochemical detector or an electrical conductivity detector. RESULTS: Lysine
      and glycine had higher reactivity to form MGO and melanoidins than arginine and
      proline. More acetic acid was produced and a higher consumption of arginine was
      observed in glucose-arginine solution. Moreover, higher pH significantly
      accelerated the formation of MGO. CONCLUSION: Amino reactivity and pH were two
      important factors affecting the formation of MGO in the Maillard reaction. (c)
      2016 Society of Chemical Industry.

PMID- 27885684
TI  - Interference-free mass spectrometric detection of capillary isoelectric focused
      proteins, including charge variants of a model monoclonal antibody.
AB  - CIEF represents an elegant technique especially for the separation of structural
      similar analytes, whereas MS is a state-of-the-art instrumentation for the
      identification and characterization of biomolecules. The combination of both
      techniques can be realized by hyphenating CIEF with CZE-ESI-MS applying a
      mechanical valve. During the CZE step, the remaining ESI-interfering components
      of the CIEF electrolyte are separated from the analytes prior to MS detection. In
      this work, a multiple heart-cut approach is presented expanding our previous
      single heart-cut concept resulting in a dramatical reduction of analysis time.
      Moreover, different sample transfer loop volumes are systematically compared and
      discussed in regard to peak width and transfer efficiency. With this major
      enhancement, model proteins (1.63-9.75 mg/L), covering a wide pI range (5-10),
      and charge variants from a deglycosylated model antibody were analyzed on intact
      level. The promising CIEF-CZE-MS setup is expected to be applicable in different
      bioanalytical fields, e.g. for the fast and information rich characterization of
      therapeutic antibodies.

PMID- 27885685
TI  - Gastric and small intestine gastrointestinal stromal tumors: Do outcomes differ?
AB  - BACKGROUND AND OBJECTIVES: Gastrointestinal stromal tumors (GISTs) are the most
      common mesenchymal tumors of the gastrointestinal tract. Previous literature has
      suggested that small intestine GISTs are more aggressive than gastric GISTs. Our
      primary objective was to compare the outcomes of gastric and small intestine
      GISTs in the decade after approval of imatinib for treatment. METHODS: The SEER
      database was queried for cases of gastric and small intestine GIST between the
      years 2002 and 2012, using the ICD-O-3 histology code 8936. Survival analysis was
      performed using generalized gamma models for time to cause-specific mortality
      (CSM). RESULTS: CSM was 14.0% for the 3,759 gastric GIST patients and 14.3% for
      the 1,848 small intestine GIST patients. Five-year survival was 82.2% and 83.3%
      for gastric and small intestine patients, respectively. The number of diagnosed
      cases of GIST increased over the course of this study, especially for tumors <5
      cm in size and in patients over age 50 years. CONCLUSIONS: In this large nation
      wide study, we found that patients with gastric and small intestine GISTs had
      similar outcomes, in contrast to previous reports. The diagnosis of GIST has
      significantly increased in the last decade, which may reflect the increased
      recognition of this entity and frequent use of imaging. J. Surg. Oncol.
      2017;115:351-357. (c) 2016 Wiley Periodicals, Inc.

PMID- 27885686
TI  - Repeated oral administration of a cathepsin K inhibitor significantly suppresses
      bone resorption in exercising horses with evidence of increased bone formation
      and maintained bone turnover.
AB  - Our investigations evaluated the effect of VEL-0230, a highly specific
      irreversible inhibitor of cathepsin K (CatK). The objectives of our study were to
      determine whether repeated dosing of a CatK inhibitor (CatKI) produced a desired
      inhibition of the bone resorption biomarker (CTX-1), and document the effect of
      repeated dosing on bone homeostasis, structure, and dynamics of bone resorption
      and formation in horses. Twelve young exercising horses were randomized in a
      prospective, controlled clinical trial and received 4 weekly doses of a CatKI or
      vehicle. Baseline and poststudy nuclear scintigraphy, blood sampling and analysis
      of plasma bone biomarkers (CTX-1 and osteocalcin), poststudy bone fluorescent
      labeling, and bone biopsy were performed. Bone specimens were further processed
      for microcomputed tomography and bone histomorphometry. Each dose of this CatKI
      transiently inhibited plasma CTX-1 (reflecting inhibition of bone collagen
      resorption) and increased bone plasma osteocalcin concentrations, with no
      detectable adverse effect on normal bone turnover in the face of exercise. Bone
      morphology, density, and formation rate were not different between control and
      treated group. Further investigation of CatK inhibition in abnormal bone turnover
      is required in animals with bone diseases.

PMID- 27885687
TI  - Isotope ratio mass spectrometry in combination with chemometrics for
      characterization of geographical origin and agronomic practices of table grape.
AB  - BACKGROUND: Although table grape is one of the most cultivated and consumed
      fruits worldwide, no study has been reported on its geographical origin or
      agronomic practice based on stable isotope ratios. This study aimed to evaluate
      the usefulness of isotopic ratios (i.e. 2 H/1 H, 13 C/12 C, 15 N/14 N and 18 O/16
      O) as possible markers to discriminate the agronomic practice (conventional
      versus organic farming) and provenance of table grape. RESULTS: In order to
      quantitatively evaluate which of the isotopic variables were more discriminating,
      a t test was carried out, in light of which only delta13 C and delta18 O provided
      statistically significant differences (P <= 0.05) for the discrimination of
      geographical origin and farming method. Principal component analysis (PCA) showed
      no good separation of samples differing in geographical area and agronomic
      practice; thus, for classification purposes, supervised approaches were carried
      out. In particular, general discriminant analysis (GDA) was used, resulting in
      prediction abilities of 75.0 and 92.2% for the discrimination of farming method
      and origin respectively. CONCLUSION: The present findings suggest that stable
      isotopes (i.e. delta18 O, delta2 H and delta13 C) combined with chemometrics can
      be successfully applied to discriminate the provenance of table grape. However,
      the use of bulk nitrogen isotopes was not effective for farming method
      discrimination. (c) 2016 Society of Chemical Industry.

PMID- 27885688
TI  - Effect of high-pressure processing and thermal pasteurization on overall quality
      parameters of white grape juice.
AB  - BACKGROUND: The aim of this study was to investigate the microbial levels,
      physicochemical and antioxidant properties and polyphenol oxidase (PPO) and
      peroxidase (POD) activities as well as to conduct a sensory analysis of white
      grape juice treated with high-pressure processing (HPP) and thermal
      pasteurization (TP), over a period of 20 days of refrigerated storage. RESULTS:
      HPP treatment of 600 MPa and TP significantly reduced aerobic bacteria, coliform
      and yeast/mold counts. At day 20 of storage, HPP-600 juice displayed no
      significant differences compared with fresh juice in terms of physicochemical
      properties such as titratable acidity, pH and soluble solids, and retained less
      than 50% PPO and POD activities. Although significant differences were observed
      in the color, antioxidant contents and antioxidant capacity of HPP-treated juice,
      the extent of these differences was substantially lower than that in TP-treated
      juice, indicating that HPP treatment can better retain the quality of grape
      juice. Sensory testing showed no significant difference between HPP-treated juice
      and fresh juice, while TP reduced the acceptance of grape juice. CONCLUSION: This
      study shows that HPP treatment maintained the overall quality parameters of white
      grape juice, thus effectively extending the shelf life during refrigerated
      storage. (c) 2016 Society of Chemical Industry.

PMID- 27885689
TI  - The role of aberrant methylation of trophoblastic stem cell origin in the
      pathogenesis and diagnosis of placental disorders.
AB  - OBJECTIVES: The objective of the study is to investigate the role of methylation
      levels at promoter regions of placental vascularization genes (VEGF, EGFR, and c
      jun) in pathogenesis and diagnosis of placental disorders. METHODS: We analyzed
      DNA and histone methylation at promoters of VEGF, EGFR, and c-jun via methylation
      sensitive high-resolution melting and chromatin immunoprecipitation assay in
      pregnant women with normal pregnancy in first, second, and third trimesters (n =
      30 in each group) and pregnant women with pregnancy complicated with preeclampsia
      (n = 30) and hydatidiform mole (n = 15). RESULTS: The higher expression of VEGF,
      EGFR, and c-jun in early pregnancy was observed to be independent of DNA
      methylation, while it was associated with H3 K9/K27 trimethylations. Also,
      abnormally higher expression of c-jun in GTDs was associated with lower H3K9me3
      level at its promoter. Under preeclampsia conditions, we observed dysregulation
      of both DNA methylation and H3 trimethylation and subsequent low expression of
      VEGF, EGFR, and c-jun. Importantly, our promoter methylation data indicated that
      VEGF may act as novel fetal DNA diagnostic marker for preeclampsia and molar
      pregnancies in maternal plasma. CONCLUSION: These findings emphasize the
      importance of dysregulated epigenetic phenomenon behind the pathologies of
      placental disorders and use of promoter region DNA methylation as an epigenetic
      marker for these pathological pregnancies. (c) 2016 John Wiley & Sons, Ltd.

PMID- 27885690
TI  - Long-term straw returning affects Nitrospira-like nitrite oxidizing bacterial
      community in a rapeseed-rice rotation soil.
AB  - Nitrospira are the most widespread and well known nitrite-oxidizing bacteria
      (NOB) and putatively key nitrite-oxidizers in acidic ecosystems. Nevertheless,
      their ecology in agriculture soils has not been well studied. To understand the
      impact of straw incorporation on soil Nitrospira-like bacterial community, a
      cloned library analysis of the nitrite oxidoreductase gene-nxrB was performed for
      a long-term rapeseed-rice rotation system. In this study, most members of the
      Nitrospira-like NOB in the paddy soils from the Wuxue field experiment station
      were phylogenetically related with Nitrospira lineages II. The Shannon diversity
      index possessed a decrease trend in the straw applied soils. The relative
      abundances of 16 OTUs (accounting 72% of the total OTUs, including 11 unique OTUs
      and 5 shared OTUs) were different between in the straw applied and control soils.
      These data suggested a selection effect from the long-term straw fertilization.
      Canonical correspondence analysis data showed that a centralized group of
      Nitrospira-like NOB OTUs in the community was partly explained by the soil
      ammonium, nitrate, available phosphorus, and the available potassium. This could
      suggest that straw fertilization led to the soil Nitrospira-like NOB community
      shift, which was correlated with the change of available nutrients in the bulk
      soil.

PMID- 27885691
TI  - Psychological need satisfaction, control, and disordered eating.
AB  - OBJECTIVES: Unfulfilled basic psychological needs have been associated with
      disordered eating behaviours, but the mechanisms underlying that associations are
      not well understood. This study examined a two-stage path model linking basic
      psychological need satisfaction to disordered eating behaviours via issues of
      control. METHODS: Female university students (N = 323; Mage  = 19.61), community
      participants (N = 371; Mage  = 29.75), and women who self-reported having been
      diagnosed with an eating disorder (ED; N = 41; Mage  = 23.88) completed measures
      of psychological need satisfaction (i.e., autonomy and competence), issues of
      control (i.e., feelings of ineffectiveness and fear of losing self-control
      [FLC]), and ED pathology. RESULTS: Path analysis revealed that unsatisfied needs
      of autonomy and competence were indirectly related to disordered eating
      behaviours through feelings of ineffectiveness and FLC. CONCLUSIONS: The results
      indicate that issues of control might be one of the mechanisms through which lack
      of psychological need satisfaction is associated with disordered eating. Although
      the model was constructed using cross-sectional data, these findings suggest
      potential targets for prevention and treatment efforts aimed at reducing
      disordered eating in young females. PRACTITIONER POINTS: Our results indicate
      that young women with chronically unfulfilled basic psychological needs might be
      vulnerable to developing disordered eating behaviours. The observed patterns
      suggest that persistent experience of need frustration may engender an internal
      sense of ineffectiveness and lack of control, which then compels individuals to
      engage in disordered eating behaviours in an attempt to regain autonomy and
      competence. Interventions for eating disorders may be most effective when
      emphasizing the promotion of people's needs for autonomy and competence.
      Limitations The model was constructed using cross-sectional data. Future
      experimental and longitudinal studies are needed to confirm the temporal sequence
      from basic psychological needs to issues of control. The sample only consisted of
      young women. Further research should explore how thwarting of psychological need
      satisfaction functions in men. Our clinical sample was small and diagnosis was
      not confirmed through clinical interview; therefore, those data should be
      interpreted with caution.

PMID- 27885692
TI  - Physiologically based pharmacokinetic model for ethyl tertiary-butyl ether and
      tertiary-butyl alcohol in rats: Contribution of binding to alpha2u-globulin in
      male rats and high-exposure nonlinear kinetics to toxicity and cancer outcomes.
AB  - In cancer bioassays, inhalation, but not drinking water exposure to ethyl
      tertiary-butyl ether (ETBE), caused liver tumors in male rats, while tertiary
      butyl alcohol (TBA), an ETBE metabolite, caused kidney tumors in male rats
      following exposure via drinking water. To understand the contribution of ETBE and
      TBA kinetics under varying exposure scenarios to these tumor responses, a
      physiologically based pharmacokinetic model was developed based on a previously
      published model for methyl tertiary-butyl ether, a structurally similar chemical,
      and verified against the literature and study report data. The model included
      ETBE and TBA binding to the male rat-specific protein alpha2u-globulin, which
      plays a role in the ETBE and TBA kidney response observed in male rats.
      Metabolism of ETBE and TBA was described as a single, saturable pathway in the
      liver. The model predicted similar kidney AUC0-infinity for TBA for various
      exposure scenarios from ETBE and TBA cancer bioassays, supporting a male-rat
      specific mode of action for TBA-induced kidney tumors. The model also predicted
      nonlinear kinetics at ETBE inhalation exposure concentrations above ~2000 ppm,
      based on blood AUC0-infinity for ETBE and TBA. The shift from linear to nonlinear
      kinetics at exposure concentrations below the concentration associated with liver
      tumors in rats (5000 ppm) suggests the mode of action for liver tumors operates
      under nonlinear kinetics following chronic exposure and is not relevant for
      assessing human risk. Copyright (c) 2016 The Authors Journal of Applied
      Toxicology Published by John Wiley & Sons Ltd.

PMID- 27885694
TI  - Pharmacokinetics and tolerability of a new formulation of omeprazole in the
      horse.
AB  - A new formulation of omeprazole in gastro-resistant granules was tested with
      regard to its pharmacokinetics and tolerability. Twenty-four horses were randomly
      divided into three groups (8 horses/group) and treated, according a parallel
      study design, as follows: Group A untreated (control group), Group B received 4
      mg/kg of omeprazole, and Group C received 12 mg/kg of omeprazole, both of which
      were treated orally once a day for 90 days. Blood samples, taken from Group B
      subjects during the 1st and the 29th day of treatment at pre-established time
      points, were used to determine the concentration-time curves of omeprazole. The
      treatments were found to be safe and well tolerated by the horses. The serum
      hematological and biochemical values were within reference ranges for the entire
      observational time. No accumulation of the drug was found after 29 days of
      treatment. Lower Cmax and AUCs were obtained at the 29th day of treatment.

PMID- 27885693
TI  - Association of single nucleotide polymorphism in melatonin receptor 1A gene with
      egg production traits in Yangzhou geese.
AB  - In the present study the melatonin receptor 1A gene (MTNR1A) was proposed to be a
      candidate gene for egg production in Yangzhou geese. A total of 210 goose blood
      samples were collected to investigate the association of the MTNR1A gene with the
      number of eggs produced. Using a direct sequencing method, a single nucleotide
      polymorphism (SNP; g.177G>C) was detected in the 5' regulatory region of the
      MTNR1A gene (Genbank ss1985399687). Two alleles (G and C) and three genotypes
      were identified. Association analysis results showed that the g.177G>C SNP
      significantly affected the level of egg production within a 34-week egg-laying
      period (P < 0.05). Furthermore, the geese with the GG genotype produced
      significantly more eggs compared to the geese with the CC genotype. Quantitative
      real-time PCR analysis showed that the MTNR1A gene was highly expressed in small
      intestine, granulosa cell and ovary compared to other examined tissues. In
      addition, the mRNA expression level of MTNR1A in ovary indicated that
      significantly higher expression levels were recorded for geese with the GG
      genotype compared to those with the CC genotype. Moreover, a luciferase reporter
      assay showed that the CC genotype had significantly lower promoter activity than
      did GG. These results suggest that the identified SNP in the MTNR1A gene may
      influence the number of eggs produced and mRNA expression levels in Yangzhou
      geese and could be considered as a useful molecular marker in goose selection and
      improvement, especially for egg production.

PMID- 27885695
TI  - Vaccination mitigates the impact of PRRSv infection on the pharmacokinetics of
      ceftiofur crystalline-free acid in pigs.
AB  - The pharmacokinetics of intramuscularly administered ceftiofur crystalline-free
      acid (CCFA) were determined in pigs that were clinically healthy (n = 8),
      vaccinated with a Porcine reproductive and respiratory syndrome modified live
      virus (PRRS MLV) (n = 10), challenged with wild-type porcine reproductive and
      respiratory syndrome virus (PRRSv) VR-2385 (n = 10), or vaccinated with PRRS MLV
      and later challenged with wild-type PRRSv VR-2385 (n = 10). Animals were given a
      single dose of CCFA intramuscularly at 5 mg/kg body weight. Blood was collected
      at 0 (pretreatment), 0.25, 0.5, 1, 6, 12, 24, 48, 96, 144, 192, and 240 h
      postinjection. Plasma was analyzed using liquid chromatography-mass spectrometry.
      Plasma concentration-time curves for each group were evaluated with
      noncompartmental modeling. When compared to control animals, those receiving the
      PRRSv wild-type challenge only had a lower AUC0-last , higher Cl/F, and higher
      Vz/F. The PRRSv wild-type challenge only group had the longest T1/2lambda . The
      Cmax did not differ among all four treatments. Control animals had no
      statistically significant differences from animals vaccinated with PRRS MLV alone
      or animals vaccinated with PRRS MLV and later challenged with wild-type PRRSv.
      Our results suggest that PRRSv wild-type infection has the potential to alter
      CCFA pharmacokinetics and PRRS MLV vaccination may attenuate those changes.

PMID- 27885696
TI  - Pharmacokinetics of oral terbinafine in adult horses.
AB  - The primary study objective was to compare the pharmacokinetics of p.o.
      terbinafine alone to p.o. terbinafine administered with p.o. cimetidine in
      healthy adult horses. The second objective was to assess the pharmacokinetics of
      terbinafine when administered per rectum in two different suspensions at 30 mg/kg
      to adult horses. Six healthy adult horses were included in this crossover study.
      Plasma terbinafine concentrations were quantified with liquid chromatography and
      mass spectrometry. The half-life (geometric mean) was 8.38 and 10.76 h, for p.o.
      alone and p.o. with cimetidine, respectively. The mean maximum plasma
      concentrations were 0.291 MUg/mL at 1.54 h and 0.418 MUg/mL at 1.28 h for p.o.
      alone and p.o. with cimetidine, respectively. Terbinafine with cimetidine had an
      average CMAX 44% higher and the relative F was 153% compared p.o. terbinafine
      alone, but was not statistically different (P > 0.05). Terbinafine was
      infrequently detected when administered per rectum in two different suspensions
      (water or olive oil). Minor adverse effects included oral irritation, fever, and
      colic. All resolved spontaneously. More pharmacokinetic studies are indicated
      assessing drug-drug interactions and using multiple dosing intervals to improve
      our knowledge of effective oral dosing, the potential for drug accumulation, and
      systemic adverse effect of terbinafine in horses.

PMID- 27885697
TI  - Dynamic effects of CYP3A5 polymorphism on dose requirement and trough
      concentration of tacrolimus in renal transplant recipients.
AB  - WHAT IS KNOWN AND OBJECTIVE: Tacrolimus is a widely used immunosuppressive drug
      with marked pharmacokinetic variability partly due to CYP3A5 polymorphism. Our
      study aimed to investigate the dynamic effects of CYP3A5 genotypes on dose
      requirement and trough concentration (C0 ) of tacrolimus in renal transplant
      recipients. METHODS: A total of 194 Chinese renal transplant recipients received
      oral tacrolimus twice daily. Whole-blood C0 of tacrolimus were measured on the
      3rd day, 7th day, 14th day, 1st month, 3rd month and 6th month post
      transplantation. CYP3A5 genotypes were determined and the recipients were
      categorized as CYP3A5 expressers (CYP3A5*1 allele carriers) and non-expressers
      (homozygous CYP3A5*3). The correlated serum creatinine, haematocrit and albumin
      were also detected. RESULTS: The allele frequencies for CYP3A5*1/*1, *1/*3 and
      *3/*3 were 7.7%, 44.8% and 47.4%, respectively. There were no significant
      variability in serum creatinine, haematocrit and albumin values between CYP3A5
      expressers and non-expressers. Larger doses were administered to CYP3A5
      expressers than to non-expressers after surgery except the initial dose. C0 were
      much lower in CYP3A5 expressers than in non-expressers on the 3rd day, 7th day,
      14th day and 1st month post-transplantation (P < 0.01); however, no significant
      differences were found on the 3rd and 6th months post-transplantation. All of the
      dose-adjusted C0 in CYP3A5 expressers were significantly lower than non
      expressers (P < 0.01). Less of the recipients achieving target C0 (4-8 ng/mL)
      were found in CYP3A5 expressers than in non-expressers after initial dose (35.7%
      vs. 50%). Meanwhile, CYP3A5 non-expressers were detected having higher C0 (>8
      ng/mL) during 3 months post-transplantation. Besides, the proportions in the two
      groups both increased gradually over time and up to 91.8% and 94% on the 6th
      month, respectively. WHAT IS NEW AND CONCLUSION: There are no significant
      differences in serum creatinine, haematocrit and albumin values between CYP3A5
      expressers and non-expressers. CYP3A5 expressers have decreased dose-adjusted
      tacrolimus C0 when compared to non-expressers. Dose-adjusted C0 of tacrolimus
      increases in a time-dependent manner in both groups.

PMID- 27885699
TI  - Strains of Group B streptococci from septic patients induce platelet activation
      via Toll-like Receptor 2.
AB  - Group B Streptococcus (GBS) causes life-threatening bacterial sepsis, especially
      in newborns and pregnant women. Patients suffering from sepsis often display low
      platelet counts, characterized by thrombocytopenia, because of platelet
      activation. In the present study, the roles of six GBS strains from septic
      patients in platelet aggregation, as well as the underlying mechanisms, were
      investigated. Incubation of platelets with three of the strains induced platelet
      aggregation, increased the secretion of cellular adhesin molecule CD62P and
      activation of GPIIb/IIIa. Furthermore, the GBS strains that induced platelet
      activation also caused an increase in the expression of Toll-like receptor (TLR)
      2 in platelets. Pre-incubation of platelets with anti-TLR2 monoclonal antibody,
      but not anti-TLR4 monoclonal antibody, inhibited these functional responses
      induced by GBS. TLR2 stimulation also activated the phosphoinositide 3-kinase
      (PI3-K)/Akt signalling pathway in platelets, and inhibition of PI3-K
      significantly reduced GBS-induced platelet responses. Our results indicate that
      three of the GBS strains from the septic patients can trigger platelet activation
      by interacting with platelets, which involves the elevation of platelet TLR2
      expression.

PMID- 27885698
TI  - Long-term excess risk of stroke in people with Type 2 diabetes in Sweden
      according to blood pressure level: a population-based case-control study.
AB  - AIMS: To estimate the risk of stroke in people with Type 2 diabetes with
      different blood pressure levels compared with the risk in the general population
      in Sweden. METHODS: This prospective case-control study included 408 076 people
      with Type 2 diabetes, aged >= 18 years, and free of prior stroke, registered in
      the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control
      subjects (n = 1 913 507) without stroke from the general population were
      included. Stroke diagnoses were retrieved using International Classification of
      Disease codes from the Swedish patient and death registers. Cox hazard ratios and
      95% confidence intervals (CIs) were estimated at six different blood pressure
      levels. RESULTS: During a median follow-up of 4 years, 19 548 (4.8%) people with
      Type 2 diabetes and 61 690 (3.2%) without diabetes were diagnosed with stroke,
      corresponding to an adjusted hazard ratio of 1.43 (95% CI 1.41-1.46) for people
      with Type 2 diabetes as a group. Compared with people without diabetes, the risk
      of stroke for people with Type 2 diabetes with different blood pressure levels
      was significantly higher, starting at blood pressure levels > 130/80 mmHg. Hazard
      ratios for stroke were 1.20 (95% CI 1.16-1.24), 1.47 (95% CI 1.43-1.50), and 1.97
      (95% CI 1.90-2.03) for blood pressure categories of 130-139/80-89 mmHg, 140
      159/90-99 mmHg and >= 160/>= 100 mmHg, respectively, after adjustment for age,
      sex, diabetes duration, being born in Sweden, maximum education level and
      baseline comorbidities. CONCLUSIONS: People with Type 2 diabetes and blood
      pressure < 130/80 mmHg had a risk of stroke similar to that of the general
      population.

PMID- 27885700
TI  - Heterogeneous Monolithic Integration of Single-Crystal Organic Materials.
AB  - Manufacturing high-performance organic electronic circuits requires the effective
      heterogeneous integration of different nanoscale organic materials with uniform
      morphology and high crystallinity in a desired arrangement. In particular, the
      development of high-performance organic electronic and optoelectronic devices
      relies on high-quality single crystals that show optimal intrinsic charge
      transport properties and electrical performance. Moreover, the heterogeneous
      integration of organic materials on a single substrate in a monolithic way is
      highly demanded for the production of fundamental organic electronic components
      as well as complex integrated circuits. Many of the various methods that have
      been designed to pattern multiple heterogeneous organic materials on a substrate
      and the heterogeneous integration of organic single crystals with their crystal
      growth are described here. Critical issues that have been encountered in the
      development of high-performance organic integrated electronics are also
      addressed.

PMID- 27885702
TI  - When I say ... critical pedagogy.

PMID- 27885701
TI  - Bifunctional Oxygen Reaction Catalysis of Quadruple Manganese Perovskites.
AB  - Bifunctional electrocatalysts for oxygen evolution/reduction reaction (OER/ORR)
      are desirable for the development of energy conversion technologies. It is
      discovered that the manganese quadruple perovskites CaMn7 O12 and LaMn7 O12 show
      bifunctional catalysis in the OER/ORR. A possible origin of the high OER activity
      is the unique surface structure through corner-shared planar MnO4 and octahedral
      MnO6 units to promote direct O?O bond formations.

PMID- 27885703
TI  - Immunological Tolerance. Part I of a Report of a Workshop on Foundational
      Concepts of Immune Regulation.
AB  - This report, the first of two, arose from a one-week workshop directed at
      discussing concepts of immune regulation, and focuses on immunological tolerance.
      We first outline the major ideas we thought sufficiently plausible to provide a
      context for discussing more controversial issues around tolerance. We then report
      on our discussion of different experiments that appear paradoxical in terms of
      the different, contemporary models of CD4 T cell inactivation/activation, and how
      such observations might be resolved in terms of insights provided by these
      contemporary models. These discussions bear on the plausibility of the Pathogen
      Associated Molecular Pattern (PAMP), Danger and Two Step, Two Signal Models for
      the activation of naive CD4 T cells. Some of the observations considered appear
      paradoxical in terms of the PAMP and Danger Models, but not with the Two Step,
      Two Signal Model. For example, genetically immunodeficient mice have been given
      foreign, sterile ectopic grafts, and the immune system allowed to develop once
      these grafts were well-healed in, and so in the absence of PAMPs or danger. The
      grafts were rejected, unexpected on the PAMP or Danger Models. We also discussed
      considerations and observations bearing on the widely held idea that antigen must
      crosslink the membrane Ig receptors of a B cell to initiate the generation of
      signal 1, or the alternative possibility that monovalent binding by antigen can
      do so. We favored the latter possibility, and discussed a particular model, "the
      Elbow Model," for how this might be achieved.

PMID- 27885704
TI  - Effects of genetic variations in the genes encoding NOD1 and NOD2 on type 2
      diabetes mellitus and insulin resistance.
AB  - WHAT IS KNOWN AND OBJECTIVE: Nucleotide-binding oligomerization domain (NOD) 1
      and NOD 2 are members of the NOD-like receptor (NLR) family and contain a caspase
      recruitment domain. NLRs are located in the cytosol, bind bacterial and viral
      ligands and play a key role in the realization of innate and adaptive immune
      response, inflammation, apoptosis and reactive oxygen species generation. Insulin
      resistance (IR) is a leading cause of type 2 diabetes mellitus (T2DM) and
      associated with obesity, inflammation and pro-inflammatory responses. NOD1 and
      NOD2 gene variants may affect the risk of chronic inflammation, insulin
      resistance and T2DM by shifting the balance between pro- and anti-inflammatory
      cytokines. The aim of our study was to determine whether the NOD1/2 gene variants
      might contribute to the risk of T2DM and IR. METHODS: The rs5743336 variant of
      NOD1 and rs2066847 variant of NOD2 were analysed by PCR-RFLP analysis in 200
      subjects (T2DM: n = 100; healthy controls: n = 100) of Turkish origin. PCR
      products were digested with the AvaI and ApaI restriction enzymes. For the NOD1
      site, the presence of the G allele was indicated by cleavage of the 379 bp
      amplified PCR product that yielded 209-bp and 170-bp fragments. For the NOD2
      site, 151-bp PCR products were cleaved and yielded 130-bp and 21-bp fragments
      when the WT-insC mutation was present. Comparisons of the genotypes between
      controls and patients were performed by chi-square tests. RESULTS AND DISCUSSION:
      The genotypes of the rs5743336 variant of NOD1 and the rs2066847 variant of NOD2
      are presented, and no significant differences were observed in the genotype
      frequencies of the NOD1 and NOD2 variants between the healthy controls and T2DM
      patients (P > 0.05). According to our preliminary data, NOD1/2 gene variants are
      not linked with T2DM and IR. WHAT IS NEW AND CONCLUSION: This study is the first
      to look for possible association of the genotype frequencies of NOD1 and NOD2
      genes with T2DM and IR. The significant finding of this report is that the
      rs5743336 and rs2066847 variations in the NOD1/2 gene are not associated with
      T2DM and IR risk in patients of Turkish origin.

PMID- 27885707
TI  - Spatial resolution and velocity field improvement of 4D-flow MRI.
AB  - PURPOSE: 4D-flow MRI obtains a time-dependent 3D velocity field; however, its use
      for the calculation of higher-order parameters is limited by noise. We present an
      algorithm for denoising 4D-flow data. THEORY AND METHODS: By integrating a
      velocity field and eliminating streamlines in noisy flow, depicted by high
      curvature, a denoised dataset may be extracted. This method, defined as the
      velocity field improvement (VFIT) algorithm, was validated in an analytical
      dataset and using in vivo data in comparison with a computation fluid dynamics
      (CFD) simulation. As a proof of principal, wall shear stress (WSS) measurements
      in the descending aorta were compared with those defined by CFD. RESULTS: The
      VFIT algorithm achieved a >100% noise reduction of a corrupted analytical
      dataset. In addition, 4D-flow data were cleaned to show improved spatial
      resolution and near wall velocity representation. WSS measures compared well with
      CFD data and bulk flow dynamics were retained (<2% difference in flow
      measurements). CONCLUSION: This study presents a method for denoising 4D-flow
      datasets with improved spatial resolution. Bulk flow dynamics are accurately
      conserved while velocity and velocity gradient fields are improved; this is
      important in the calculation of higher-order parameters such as WSS, which are
      shown to be more comparable to CFD measures. Magn Reson Med 78:1959-1968, 2017.
      (c) 2016 International Society for Magnetic Resonance in Medicine.

PMID- 27885705
TI  - Multiple linear combination (MLC) regression tests for common variants adapted to
      linkage disequilibrium structure.
AB  - By jointly analyzing multiple variants within a gene, instead of one at a time,
      gene-based multiple regression can improve power, robustness, and interpretation
      in genetic association analysis. We investigate multiple linear combination (MLC)
      test statistics for analysis of common variants under realistic trait models with
      linkage disequilibrium (LD) based on HapMap Asian haplotypes. MLC is a
      directional test that exploits LD structure in a gene to construct clusters of
      closely correlated variants recoded such that the majority of pairwise
      correlations are positive. It combines variant effects within the same cluster
      linearly, and aggregates cluster-specific effects in a quadratic sum of squares
      and cross-products, producing a test statistic with reduced degrees of freedom
      (df) equal to the number of clusters. By simulation studies of 1000 genes from
      across the genome, we demonstrate that MLC is a well-powered and robust choice
      among existing methods across a broad range of gene structures. Compared to
      minimum P-value, variance-component, and principal-component methods, the mean
      power of MLC is never much lower than that of other methods, and can be higher,
      particularly with multiple causal variants. Moreover, the variation in gene
      specific MLC test size and power across 1000 genes is less than that of other
      methods, suggesting it is a complementary approach for discovery in genome-wide
      analysis. The cluster construction of the MLC test statistics helps reveal within
      gene LD structure, allowing interpretation of clustered variants as haplotypic
      effects, while multiple regression helps to distinguish direct and indirect
      associations.

PMID- 27885708
TI  - Oldest medical description of osteogenesis imperfecta (17th Century, France).
AB  - Osteogenesis imperfecta (OI), also known as Lobstein's syndrome or Vrolik's
      syndrome, comprises a heterogeneous group of rare genetic connective tissue
      disorders. It is characterized by increased bone fragility, low bone mass, and
      susceptibility to bone fractures of variable severity. Originally named
      "osteomalacia congenita," the condition was first medically described in a family
      by Ekman in 1778. Here, we report a 17th century medical account from France,
      which predates Eckman's doctoral dissertation by about a century. Medical
      analysis of this anatomical presentation indicates a precise diagnosis of Type I
      OI. Clin. Anat. 30:128-129, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27885706
TI  - Insulin pump failures in Italian children with Type 1 diabetes: retrospective 1
      year cohort study.
AB  - AIMS: Insulin pump failure and/or malfunction requiring replacement have not been
      thoroughly investigated. This study evaluated pump replacement in children and
      adolescents with Type 1 diabetes using insulin pump therapy. METHODS: Data were
      collected for all participants younger than 19 years, starting insulin pump
      therapy before 31 December 2013. For each child, age, disease duration, date of
      insulin pump therapy initiation, insulin pump model,
      failure/malfunction/replacement yes/no and reason were considered for the year
      2013. RESULTS: Data were returned by 40 of 43 paediatric centres belonging to the
      Diabetes Study Group of the Italian Society of Paediatric Endocrinology and
      Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type
      1 diabetes were using an insulin pump: 29.2% Animas VIBETM , 9.4% Medtronic
      MiniMed 715/515TM , 34.3% Medtronic MiniMed VEOTM , 24.3% Accu-Check Spirit
      ComboTM and 2.8% other models. In 2013, 0.165 insulin pump replacements per
      patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental
      damage) were recorded. Animas VIBETM (22.1%) and Medtronic MiniMed VEOTM (17.7%)
      were the most replaced. CONCLUSIONS: In a large cohort of Italian children and
      adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent
      replacement are aligned with rates previously reported and higher in more
      sophisticated pump models.

PMID- 27885710
TI  - Clinical imaging of macular pigment optical density and spatial distribution.
AB  - Clinical research continues to provide an increasing number of studies that
      reveal an association between macular pigment optical density (MPOD) and both
      visual function and ocular health. As a result, there is a growing need for
      repeatable, accurate measures of MPOD that can describe peak optical density as
      well as spatial distribution. Measurement of MPOD in a research setting has an
      established history encompassing a number of both objective and subjective
      techniques. Transition of these techniques to a clinical setting has produced an
      array of commercial devices using three primary methods: heterochromatic flicker
      photometry, fundus autofluorescence and fundus reflectometry. The inherent
      differences among the techniques create difficulty in making direct comparisons
      between MPOD measurement devices. Understanding the limitations of each technique
      is critical in the clinical interpretation of MPOD results. Here, both the
      objective and subjective methods of MPOD measurement are reviewed with emphasis
      on the commercially available devices used in clinical settings.

PMID- 27885711
TI  - The Importance of Research and Scholarly Activity in Pharmacy Training.
AB  - Regardless of practice setting, it is imperative that pharmacists be able to
      either participate in generating new knowledge or use the ever-expanding body of
      literature to guide patient care. However, competing priorities in Pharm.D.
      curricula and residency training programs have resulted in limited emphasis on
      acquiring research and scholarly skills. Factors likely contributing to this
      reduced focus include the lack of curricular and postgraduate training standards
      emphasizing the development of research skills, time to commit to scholarly
      activity, and accessibility to experienced mentors. Strategies for increasing
      scholarly activity for pharmacy students and residents should therefore continue
      to be a focus of professional degree and residency training programs. Several
      resources are available for academic planners, program directors, and
      institutions to augment scholarly experience for pharmacy trainees and
      clinicians. This commentary highlights the importance of providing research
      opportunities for students and residents, describes the potential barriers to
      these activities, and provides recommendations on how to increase the instruction
      and mentoring of trainees to generate and use research.

PMID- 27885709
TI  - The median hazard ratio: a useful measure of variance and general contextual
      effects in multilevel survival analysis.
AB  - Multilevel data occurs frequently in many research areas like health services
      research and epidemiology. A suitable way to analyze such data is through the use
      of multilevel regression models (MLRM). MLRM incorporate cluster-specific random
      effects which allow one to partition the total individual variance into between
      cluster variation and between-individual variation. Statistically, MLRM account
      for the dependency of the data within clusters and provide correct estimates of
      uncertainty around regression coefficients. Substantively, the magnitude of the
      effect of clustering provides a measure of the General Contextual Effect (GCE).
      When outcomes are binary, the GCE can also be quantified by measures of
      heterogeneity like the Median Odds Ratio (MOR) calculated from a multilevel
      logistic regression model. Time-to-event outcomes within a multilevel structure
      occur commonly in epidemiological and medical research. However, the Median
      Hazard Ratio (MHR) that corresponds to the MOR in multilevel (i.e., 'frailty')
      Cox proportional hazards regression is rarely used. Analogously to the MOR, the
      MHR is the median relative change in the hazard of the occurrence of the outcome
      when comparing identical subjects from two randomly selected different clusters
      that are ordered by risk. We illustrate the application and interpretation of the
      MHR in a case study analyzing the hazard of mortality in patients hospitalized
      for acute myocardial infarction at hospitals in Ontario, Canada. We provide R
      code for computing the MHR. The MHR is a useful and intuitive measure for
      expressing cluster heterogeneity in the outcome and, thereby, estimating general
      contextual effects in multilevel survival analysis. (c) 2016 The Authors.
      Statistics in Medicine published by John Wiley & Sons Ltd.

PMID- 27885712
TI  - Randomized controlled trial comparing lactulose plus albumin versus lactulose
      alone for treatment of hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy (HE) is associated with poor prognosis and
      treatment of HE is primarily directed at the reduction of the blood ammonia
      levels. The study evaluated the efficacy and safety of albumin plus lactulose
      versus lactulose alone for treatment of overt HE. METHODS: In prospective
      randomized controlled trial, 120 patients with overt HE were randomized in two
      groups: group A lactulose plus albumin (n = 60) and group B lactulose alone (n =
      60). Primary end point was complete reversal of HE, and secondary end points were
      mortality and hospital stay. RESULTS: A total of 120 patients (mean age 40.4 +/-
      9.3 years) were included in this study. Thirty-six (30%) patients were in Child
      Turcotte-Pugh (CTP) class B, and 84 (70%) were in CTP Class C. Mean CTP score was
      9.8 +/- 2.1, and model for end-stage liver disease score was 26.1 +/- 5.3. Twenty
      seven (22.5%) had grade 2, 57 (47.5%) had grade 3, and 36 (30%) had grade 4 HE at
      the time of admission. Forty-five (75%) patients in group A compared with 32
      (53.3%) patients in group B had complete reversal of HE (P = 0.03). Mortality was
      significantly lower in lactulose plus albumin group (11[18.3%]) versus lactulose
      alone (19 [31.6%], [P < 0.05]). There was significant decrease in levels of
      arterial ammonia, interleukin-6, interleukin-18, tumor necrosis factor-alpha, and
      endotoxins after treatment in both groups; however, the delta decrease was
      significantly higher in group A compared with group B. Hospital stay was shorter
      in group A. CONCLUSIONS: Combination of lactulose plus albumin is more effective
      than lactulose alone in treatment of overt HE.

PMID- 27885713
TI  - A new tool to quantify the geometrical characteristics of facial skin pores.
      Changes with age and a making-up procedure in Caucasian women.
AB  - BACKGROUND: Facial skin pores (FSP) are common and benign signs that generate
      frequent esthetic concerns or complaints. Despite their worldwide prevalence,
      related literature remains scarce. Hence, a new device has been developed and
      applied to validating studies, aiming at best describing FSP as they are self
      perceived, i.e. their anatomic features, their possible alterations with age and
      their appearance after application of a make-up product. METHODS: Dermascore+(r)
      is an imaging device dedicated to a direct observation and acquisition of various
      characteristics of the skin surface. Images are captured under a high
      magnification and under different lighting configurations, to highlight the skin
      relief, based upon parallel polarized images. Dedicated software allows FSP to
      being detected and their morphological parameters to being extracted and
      computed. By measuring each detected FSP in a given region of interest, a
      statistically significant impact of both age and an applied cosmetic product upon
      their morphological features can be observed and quantified. RESULTS: Although
      the size and density of FSP are not affected by aging, their shape becomes
      elongated. A few tested make up products show variable effects that closely
      correlate with visual assessments made by trained estheticians. CONCLUSION: The
      shape of FSP present on cheeks shows age-related changes, toward a more elongated
      aspect, likely linked to a progressively altered (more isotropic) skin surface
      micro-relief. The new tool Dermascore+(r) allows foundations to being rapidly
      differentiated and screened according to their variable effects upon the visual
      appearance through instrumental, objective depiction of FSP.

PMID- 27885714
TI  - High-Performance THz Emitters Based on Ferromagnetic/Nonmagnetic
      Heterostructures.
AB  - A low-cost, intense, broadband, noise resistive, magnetic field controllable,
      flexible, and low power driven THz emitter based on thin
      nonmagnetic/ferromagnetic metallic heterostructures is demonstrated. The THz
      emission origins from the inverse spin Hall Effect. The proposed devices are not
      only promising for a wide range of THz equipment, but also offer an alternative
      approach to characterize the spin-orbit interaction in nonmagnetic/ferromagnetic
      bilayers.

PMID- 27885715
TI  - Response to: The two faces of the translaminar pressure difference: the
      biomechanical one and the biochemical one.

PMID- 27885716
TI  - Organic Planar Heterojunctions: From Models for Interfaces in Bulk
      Heterojunctions to High-Performance Solar Cells.
AB  - Recent progress regarding planar heterojunctions (PHJs) is reviewed, with respect
      to the fundamental understanding of the photophysical processes at the
      donor/acceptor interfaces in organic photovoltaic devices (OPVs). The current
      state of OPV research is summarized and the advantages of PHJs as models for
      exploring the relationship between organic interfaces and device characteristics
      described. The preparation methods and the characterization of PHJ structures to
      provide key points for the appropriate handling of PHJs. Next, we describe the
      effects of the donor/acceptor interface on each photoelectric conversion process
      are reviewed by examining various PHJ systems to clarify what is currently known
      and not known. Finally, it is discussed how we the knowledge obtained by studies
      of PHJs can be used to overcome the current limits of OPV efficiency.

PMID- 27885717
TI  - Salsalate treatment for prediabetes: a therapeutic alternative?

PMID- 27885719
TI  - Targeting Nanocarriers with Anisamide: Fact or Artifact?
AB  - Encapsulating chemotherapeutics in nanoparticles can reduce the side effects of
      intravenous administration and improve their antitumor efficacy. Additionally,
      surface decoration of the nanocarriers with tumor-targeting ligands may enhance
      their specificity for cancer cells overexpressing the corresponding ligand
      binding counterpart. The focus here is on anisamide, a low-molecular-weight
      benzamide derivative used as a tumor-directing moiety in functionalized
      nanosystems, based on its alleged interaction with Sigma receptors. The
      scintigraphic agents that initially inspired the use of anisamide for tumor
      targeting are described, and the published anisamide-tethered nanocarrier
      formulations are reviewed, together with a critical overview of the ligand's
      tumor-targeting properties. Moreover, anisamide's putative but dubious cellular
      target, the Sigma-1 receptor, is discussed with regard to its subcellular
      localization and implications in cancer. Data from in vivo studies reveal that
      the effect of anisamide on the antitumor efficacy of the decorated nanosystems
      varies considerably among the published reports. Together with the evidence
      questioning the interaction of anisamide with the Sigma receptors, the
      variability of anisamide's effect on the tumor deposition and the antitumor
      efficacy of the decorated drug carriers calls into question the extent of the
      ligand's tumor-targeting effect. Further research is necessary to elucidate the
      ligand's utility in tumor targeting.

PMID- 27885718
TI  - Purinergic receptors: new targets for the treatment of gout and fibrosis.
AB  - Adenosine triphosphate is involved in many metabolic reactions, but it has also a
      role as a cellular danger signal transmitted through purinergic receptors (PRs).
      Indeed, adenosine 5'-triphosphate (ATP) can bind to PRs which are found in the
      membrane of many cell types, although the relative proportions of the receptor
      subtypes differ. PRs are classified according to genetic and pharmacological
      criteria and especially their affinities for agonists and their transduction
      mechanism (i.e. as metabotropic P2YRs or ionotropic P2XRs). Extracellular ATP
      release by activated or necrotic cells may activate various PRs and especially
      P2X7R, the best-characterized PR, on immune cells. P2X7R is known to regulate the
      activation of the Nod-like receptor (NLR)-family protein, NLRP3 inflammasome,
      which permit the release of IL-1beta, a potent pro-inflammatory cytokine. The
      P2X7R/NLRP3 pathway is involved in many inflammatory diseases, such as gout, and
      in fibrosis diseases associated with inflammatory process, liver or lung
      fibrosis. Some authors imaging also a real promising therapeutic potential of
      P2X7R blockage. Thus, several pharmaceutical companies have developed P2X7R
      antagonists as novel anti-inflammatory drug candidates. Clinical trials of the
      efficacy of these antagonists are now underway. A better understanding of the
      P2X7R/NLRP3 signalling pathways permits the identification of targets and the
      development of a new class of drugs able to inhibit the fibrogenesis process and
      collagen deposition.

PMID- 27885720
TI  - A retrospective clinical study of endoscopic-assisted transcervical insemination
      in the bitch with frozen-thawed dog semen.
AB  - Since the conclusion of data collation from previously published work, a further
      352 inseminations using frozen-thawed dog semen by endoscopic-assisted
      transcervical insemination (EIU) have been performed by the author. Insemination
      was performed on the second day in which crenulation of the anterior vagina was
      detected in conjunction with a progesterone concentration of >10 ng/ml. All semen
      samples were analysed for total number of sperm, total motility and progressive
      motility using computer-assisted semen analysis (CASA). The insemination dose was
      based on the progressively motile normal spermatozoa (PMNS). Insemination was
      performed on all bitches as previously described using a ureterorenoscope.
      Additional extender was inseminated subsequent to the semen to expand and fill
      the uterus. The semen and additional extender were inseminated slowly over a
      period of 15-20 min. Pregnancy was determined by B-mode ultrasound equipped with
      a 7.5-MHz probe whilst standing and/or via the whelping rate. The number of sperm
      inseminated ranged from 9 * 106 PMNS to 519 * 106 PMNS, with progressive motility
      values ranging between 20% and 80%. The overall pregnancy rate was 68% (238/352).
      When stratified by PMNS, pregnancy rates were as follows: >150 * 106 PMNS - 76%
      (110/145), 100-150 * 106 - 68% (87/128) and <100 * 106 PMNS - 52% (41/79).
      Pregnancy rate was significantly higher when >150 * 106 PMNS (p = .003) or 100
      150 *106 PMNS (p = .027) were inseminated compared to <100 * 106 PMNS. These data
      are concordant with previous reports recommending the insemination of >150 * 106
      PMNS to maximize pregnancy rate. These results indicate that one optimally timed
      EIU insemination results in similar pregnancy rates to previous publications of
      one optimally timed, or two or more non-optimally timed inseminations using the
      Norwegian catheter.

PMID- 27885721
TI  - Physicochemical and Electronic Properties of Cationic [6]Helicenes: from Chemical
      and Electrochemical Stabilities to Far-Red (Polarized) Luminescence.
AB  - The physicochemical properties of cationic dioxa (1), azaoxa (2), and diaza (3)
      [6]helicenes demonstrate a much higher chemical stability of the diaza adduct 3
      (pKR+ =20.4, Ered1/2 =-0.72 V) compared to its azaoxa 2 (pKR+ =15.2, Ered1/2 =
      0.45 V) and dioxa 1 (pKR+ =8.8, Ered1/2 =-0.12 V) analogues. The fluorescence of
      these cationic chromophores is established, and ranges from the orange to the far
      red regions. From 1 to 3, a bathochromic shift of the lowest energy transitions
      (up to 614 nm in acetonitrile) and an enhancement of the fluorescence quantum
      yields and lifetimes (up to 31 % and 9.8 ns, respectively, at 658 nm) are
      observed. The triplet quantum yields and circularly polarized luminescence are
      also reported. Finally, fine tuning of the optical properties of the diaza
      [6]helicene core is achieved through selective and orthogonal post
      functionalization reactions (12 examples, compounds 4-15). The electronic
      absorption is modulated from the orange to the far-red spectral range (560-731
      nm), and fluorescence is observed from 591 to 755 nm with enhanced quantum
      efficiency up to 70 % (619 nm). The influence of the peripheral auxochrome
      substituents is rationalized by first-principles calculations.

PMID- 27885722
TI  - Thrombin-Responsive Transcutaneous Patch for Auto-Anticoagulant Regulation.
AB  - A thrombin-responsive closed-loop patch is developed for prolonged heparin
      delivery in a feedback-controlled manner. This microneedle-based patch can sense
      activated thrombin and subsequently releases heparin to prevent coagulation in
      the blood flow. This "smart" heparin patch can be transcutaneously inserted into
      skin without drug leakage and can sustainably regulate blood coagulation in
      response to thrombin.

PMID- 27885723
TI  - Formation of Onion-Like NiCo2 S4 Particles via Sequential Ion-Exchange for Hybrid
      Supercapacitors.
AB  - Onion-like NiCo2 S4 particles with unique hollow structured shells are
      synthesized by a sequential ion-exchange strategy. With the structural and
      compositional advantages, these unique onion-like NiCo2 S4 particles exhibit
      enhanced electrochemical performance as an electrode material for hybrid
      supercapacitors.

PMID- 27885724
TI  - Identification of lactoferrin and glutamate receptor-interacting protein 1 in
      bovine cervical mucus: A putative marker for oestrous detection.
AB  - Accurate detection of oestrus is important for artificial insemination. The aim
      of this study was to identify oestrous-specific bovine cervical mucus proteins
      that could be used to determine the optimal time for artificial insemination. Non
      oestrous and controlled internal drug release (CIDR)-induced oestrous-stage mucus
      proteins were purified and subjected to surface-enhanced laser
      desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulphate
      polyacrylamide gel electrophoresis and MALDI-TOF/TOF. Among differentially
      expressed proteins, lactoferrin (LF) and glutamate receptor-interacting protein 1
      (GRIP1) showed a twofold increase during the CIDR-induced oestrous stage compared
      to the levels in non-oestrous stage in bovine cervical mucus. The RT-PCR, Western
      blotting and immunohistochemistry results showed that LF and GRIP1 expression was
      significantly increased during the oestrous stage in the uterus. This study
      demonstrated that bovine LF and GRIP1 exist during the oestrous stage, but not
      during the non-oestrous stage, suggesting that cervical mucus LF and GRIP1 are
      useful oestrous detection markers in cattle.

PMID- 27885725
TI  - Recyclable and Green Triboelectric Nanogenerator.
AB  - A recyclable and green triboelectronic nanogenerator (TENG) is developed based on
      triboelectrification and designed cascade reactions. Once triggered by water, the
      TENG can fully dissolve and degrade into environmentally benign end products.
      With features of rapid dissolution, reproductivity, and green electronic, the
      TENG has potential of serving as clearable energy harvester and nanosensor for
      health monitoring and motion sensing.

PMID- 27885726
TI  - Cryopreservation of feline oocytes by vitrification using commercial kits and
      slush nitrogen technique.
AB  - Assisted reproductive techniques are a valuable tool for conservation breeding of
      endangered species. Cryopreservation methods are the basis of gamete banks,
      supporting genetic diversity preservation. Unfortunately, cryopreservation of
      feline oocytes is still considered an experimental technique. The aim of this
      study was to compare two commercial kits, with our protocol for vitrification of
      cat oocytes (IZW), which comprises a three-step method with ethylene glycol,
      DMSO, fetal calf serum, trehalose and Ficoll PM-70. Furthermore, we applied slush
      nitrogen (SN2 ) for ultra-rapid freezing to improve survival rates. Cumulus
      oocyte complexes were collected from domestic cat ovaries by slicing and
      vitrified at immature stage using Cryotop as storage device. Vit Kit(r)
      Freeze/Thaw (n = 89) showed the lowest maturation percentage obtained after
      warming (10.1%). A significant difference in maturation percentage of oocytes was
      found between Kitazato(r) kit (38.7%, n = 137) and IZW protocol (24.5%, n = 143).
      The cleavage after ICSI of warmed and matured oocytes (20.7% and 28.6%,
      respectively) and the morula percentage (18. 2% and 22.5%, respectively),
      however, did not reveal any significant difference between the two methods.
      Application of SN2 did not result in any improvement of oocytes'
      cryopreservation. Maturation percentage of the oocytes vitrified by IZW method
      with SN2 (n = 144) decreased until 6.1%, without any cleavage after
      fertilization. For Kitazato(r) (n = 62), only 17.7% were able to undergo
      maturation and cleavage percentage dropped to 18.2%, not reaching morula stage.
      These data demonstrate that feline oocytes can be vitrified either by our IZW
      method or by commercial Kitazato(r) kit, but the use of SN2 is improving neither
      maturation nor cleavage percentages when combined with these procedures.

PMID- 27885727
TI  - Growth inhibitory and proapoptotic effects of l-asparaginase from Fusarium
      culmorum ASP-87 on human leukemia cells (Jurkat).
AB  - The objective of this study was to evaluate the anticancer properties of l
      asparaginase purified from fungal isolate Fusarium culmorum ASP-87 against human
      T-cell leukemia cell line (Jurkat). The growth inhibitory and proapoptotic
      effects of purified l-asparaginase on Jurkat cell lines were investigated by
      determining its influence on cell viability, colony formation, DNA fragmentation,
      and cell cycle progression. The results revealed that purified l-asparaginase
      showed significant decrease in cell survival with IC50 value of 90 MUg/mL (9
      IU/mL). The enzyme inhibited colony formation and showed characteristic laddering
      pattern on agarose gel thereby confirming the induction of apoptosis. Further,
      cell cycle analysis revealed that the enzyme induced apoptotic cell death by
      arresting the growth of cells at G2 -M phase. However, the enzyme did not elicit
      any toxic effects on human erythrocytes. l-asparaginase purified from F. culmorum
      ASP-87 showed significant and selective cytotoxic and apoptotic effects on human
      T-cell leukemic cells in dose-dependent manner. Results of the study give leads
      for the anticancer effects of fungal l-asparaginase and its potential usefulness
      in the chemotherapy of leukemia.

PMID- 27885728
TI  - Tailoring Graphene Oxide-Based Aerogels for Efficient Solar Steam Generation
      under One Sun.
AB  - Graphene oxide-based aerogels with carefully tailored properties are developed to
      enable efficient solar steam generation. Aerogels, with inherent porous
      structures, are excellent thermal insulators and provide channels for water
      supply and vapor escape. With enhanced absorption and hydrophilicity by
      incorporation of carbon nanotubes and sodium alginate, the resulting aerogels can
      enable efficient (~83%) solar steam generation under one-sun illumination.

PMID- 27885730
TI  - Artificial Olfactory System for Trace Identification of Explosive Vapors Realized
      by Optoelectronic Schottky Sensing.
AB  - A rapid, ultrasensitive artificial olfactory system based on an individual
      optoelectronic Schottky junction is demonstrated for the discriminative detection
      of explosive vapors, including military explosives and improvised explosives.

PMID- 27885729
TI  - New biosourced chiral molecularly imprinted polymer: Synthesis, characterization,
      and evaluation of the recognition capacity of methyltestosterone.
AB  - New biosourced chiral cross-linkers were reported for the first time in the
      synthesis of methyltestosterone (MT) chiral molecularly imprinted polymers
      (cMIPs). Isosorbide and isomannide, known as 1,4:3,6-dianhydrohexitols, were
      selected as starting diols. The cMIPs were synthesized following a noncovalent
      approach via thermal radical polymerization and monitored by Raman spectroscopy.
      These cross-linkers were fully characterized by 1 H and 13 C nuclear magnetic
      resonance (NMR) spectroscopy and high-resolution mass spectrometry. The cross
      polarization magic angle spinning 13 C NMR, Fourier transform infrared
      spectroscopy, scanning electron microscopy, and specific surface areas following
      the Brunauer-Emmett-Teller (BET) method were used to characterize the cMIPs. The
      effect of stereochemistry of cross-linkers on the reactivity of polymerization,
      morphology, and adsorption-recognition properties of the MIP was evaluated. The
      results showed that the cMIP exhibited an obvious improvement in terms of
      rebinding capacity for MT as compared with the nonimprinted polymer (NIP). The
      highest binding capacity was observed for cMIP-Is (27.298 mg g-1 ) for high
      concentrations (500 mg L-1 ). However, the isomannide homologue cMIP-Im showed
      higher recovery-up to 65% and capacity for low concentrations (15 mg L-1 ). The
      experimental data were properly fitted by the Freundlich adsorption isothermal
      model.

PMID- 27885731
TI  - Development of a Nucleotide Exchange Inhibitor That Impairs Ras Oncogenic
      Signaling.
AB  - Despite more than three decades of intense effort, no anti-Ras therapies have
      reached clinical application. Contributing to this failure has been an
      underestimation of Ras complexity and a dearth of structural information. In this
      regard, recent studies have revealed the highly dynamic character of the Ras
      surface and the existence of transient pockets suitable for small-molecule
      binding, opening up new possibilities for the development of Ras modulators.
      Herein, a novel Ras inhibitor (compound 12) is described that selectively impairs
      mutated Ras activity in a reversible manner without significantly affecting wild
      type Ras, reduces the Ras-guanosine triphosphate (GTP) levels, inhibits the
      activation of the mitogen-activated protein kinase (MAPK) pathway, and exhibits
      remarkable cytotoxic activity in Ras-driven cellular models. The use of molecular
      dynamics simulations and NMR spectroscopy experiments has enabled the molecular
      bases responsible for the interactions between compound 12 and Ras protein to be
      explored. The new Ras inhibitor binds partially to the GTP-binding region and
      extends into the adjacent hydrophobic pocket delimited by switch II. Hence, Ras
      inhibitor 12 could represent a new compound for the development of more
      efficacious drugs to target Ras-driven cancers; a currently unmet clinical need.

PMID- 27885733
TI  - S-Doped N-Rich Carbon Nanosheets with Expanded Interlayer Distance as Anode
      Materials for Sodium-Ion Batteries.
AB  - 2D composites with S doping into N-rich carbon nanosheets are fabricated, whose
      interlayer distance becomes large enough for Na+ insertion and diffusion. The
      large surface area and stable structure also provide more sites for Na+
      adsorption, leading to high Na-storage capacity and excellent rate performance.
      Moreover, Faradaic reactions between Na+ and tightly bound S is beneficial for
      further improvement of Na-storage capacity.

PMID- 27885732
TI  - Surface-Charge-Mediated Formation of H-TiO2 @Ni(OH)2 Heterostructures for High
      Performance Supercapacitors.
AB  - An electrochemically favorable Ni(OH)2 with porously hierarchical structure and
      ultrathin nanosheets in a core-shell structure H-TiO2 @Ni(OH)2 is achieved
      through modulating the surface chemical activity of TiO2 by hydrogenation, which
      creates a defect-rich surface of TiO2 , thereby facilitating the subsequent
      nucleation and growth of Ni(OH)2 . These configuration-tailored H-TiO2 @Ni(OH)2
      core-shell nanowires exhibit a superior electrochemical performance and good
      flexibility.

PMID- 27885734
TI  - Simultaneous determination of thermodynamic and kinetic parameters of
      aminopolycarbonate complexes of cobalt(II) and nickel(II) based on isothermal
      titration calorimetry data.
AB  - The influence of the different side chain residues on the thermodynamic and
      kinetic parameters for complexation reactions of the Co2+ and Ni2+ ions has been
      investigated by using the isothermal titration calorimetry (ITC) technique
      supported by potentiometric titration data. The study was concerned with the 2
      common tripodal aminocarboxylate ligands, namely, nitrilotriacetic acid and N-(2
      hydroxyethyl) iminodiacetic acid. Calorimetric measurements (ITC) were run in the
      2-(N-morpholino)ethanesulfonic acid hydrate (2-(N-morpholino) ethanesulfonic
      acid), piperazine-N,N'-bis(2-ethanesulfonic acid), and dimethylarsenic acid
      buffers (0.1 mol L-1 , pH 6) at 298.15 K. The quantification of the metal-buffer
      interactions and their incorporation into the ITC data analysis enabled to obtain
      the pH-independent and buffer-independent thermodynamic parameters (K, DeltaG,
      DeltaH, and DeltaS) for the reactions under study. Furthermore, the kinITC method
      was applied to obtain kinetic information on complexation reactions from the ITC
      data. Correlations, based on kinetic and thermodynamic data, between the kinetics
      of formation of Co2+ and Ni2+ complexes and their thermodynamic stabilities are
      discussed.

PMID- 27885736
TI  - Palladium Nanoparticles Encapsulated in Hollow Titanosilicate Spheres as an Ideal
      Nanoreactor for One-pot Oxidation.
AB  - One-pot reaction involving Pd-catalyzed H2 O2 production from H2 and O2 and Ti
      catalyzed successive oxidation with H2 O2 in a single reaction vessel is an
      alluring strategy for the synthesis of targeted chemicals in terms of
      sustainability and economic competitiveness. In this study, a yolk-shell
      nanostructured catalyst, consisting of Pd nanoparticles (NPs) with core diameter
      ca. 4.0 nm and a porous titanosilicate shell of ca. 15 nm thickness, was
      fabricated by using an oil-in-water (O/W) microemulsion-based interfacial self
      assembly approach. Compared with prototype titanosilicate-supported Pd NP
      catalysts and core-shell structured analogues, the yolk-shell nanostructured
      catalyst exhibited superior catalytic efficiency in the one-pot oxidation
      reaction of sulfides with 83 % H2 O2 utilization efficiency, because of the
      productive effect of the titanosilicate shell in limiting the diffusion of H2 O2
      generated in situ over the encapsulated Pd NPs and the efficient access of the H2
      O2 to the neighboring active Ti sites. This study provides promising avenues for
      the development of multifunctional nanostructured catalysts that are useful for
      one-pot reactions.

PMID- 27885737
TI  - A Zirconium Macrocyclic Metal-Organic Framework with Predesigned Shape-Persistent
      Apertures.
AB  - A microporous metal-organic framework (MOF) was synthesized from [Zr6 O4 (OH)4
      (C6 H5 COO)12 ] clusters and a triacid ligand based on a shape-persistent arylene
      ethynylene macrocycle. This framework, dubbed Zr-MCMOF, is held together by metal
      ligand coordination and multiple weak interactions: hydrogen bonding, [pi???pi]
      stacking, and [C-H???pi] interactions. The rigid ligand has a 9 A-wide central
      void, which serves as a predesigned aperture for the 1D channels; all of the
      porosity of Zr-MCMOF comes from the ligand. The resulting framework possesses
      high hydrolytic and thermal stability and a flexible structure unique among Zr
      based MOFs.

PMID- 27885735
TI  - Small acidic protein 1 and SCFTIR1 ubiquitin proteasome pathway act in concert to
      induce 2,4-dichlorophenoxyacetic acid-mediated alteration of actin in Arabidopsis
      roots.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D), a functional analogue of auxin, is used
      as an exogenous source of auxin as it evokes physiological responses like the
      endogenous auxin, indole-3-acetic acid (IAA). Previous molecular analyses of the
      auxin response pathway revealed that IAA and 2,4-D share a common mode of action
      to elicit downstream physiological responses. However, recent findings with 2,4-D
      specific mutants suggested that 2,4-D and IAA might also use distinct pathways to
      modulate root growth in Arabidopsis. Using genetic and cellular approaches, we
      demonstrate that the distinct effects of 2,4-D and IAA on actin filament
      organization partly dictate the differential responses of roots to these two
      auxin analogues. 2,4-D but not IAA altered the actin structure in long-term and
      short-term assays. Analysis of the 2,4-D-specific mutant aar1-1 revealed that
      small acidic protein 1 (SMAP1) functions positively to facilitate the 2,4-D
      induced depolymerization of actin. The ubiquitin proteasome mutants tir1-1 and
      axr1-12, which show enhanced resistance to 2,4-D compared with IAA for inhibition
      of root growth, were also found to have less disrupted actin filament networks
      after 2,4-D exposure. Consistently, a chemical inhibitor of the ubiquitin
      proteasome pathway mitigated the disrupting effects of 2,4-D on the organization
      of actin filaments. Roots of the double mutant aar1-1 tir1-1 also showed enhanced
      resistance to 2,4-D-induced inhibition of root growth and actin degradation
      compared with their respective parental lines. Collectively, these results
      suggest that the effects of 2,4-D on actin filament organization and root growth
      are mediated through synergistic interactions between SMAP1 and SCFTIR1 ubiquitin
      proteasome components.

PMID- 27885738
TI  - A collaborative exploration of the reasons for lower satisfaction with services
      among Bangladeshi and Pakistani social care users.
AB  - This study explored underlying reasons for the expression of dissatisfaction with
      services among Bangladeshi and Pakistani social care users in England and
      investigated, using a collaborative approach, how these could be addressed. In
      depth interviews were conducted in Birmingham, Leeds and London during 2012-2013
      with 63 Bangladeshi, Pakistani and white British service users and 24 social care
      managers, social workers and care workers. A further 34 cognitive interviews were
      conducted within the same study. Following data analysis, three collaborative
      workshops involving service users and providers were held to validate the
      findings and to draw out policy and practice recommendations. Analysis of the
      cognitive interviews showed that higher dissatisfaction among Bangladeshi and
      Pakistani service users reported in social care surveys was not due to
      questionnaire design. Instead in-depth interviews showed that dissatisfaction
      across all three groups was expressed along the social care journey, including
      accessing care, communication with social workers and the nature of care
      received. While many issues were common to all three groups, cultural differences
      also emerged as affecting experiences of social care. These included
      misunderstandings about family roles in care; gender issues, especially relating
      to women; language and communication barriers, alongside the need for a more
      nuanced approach to ethnic 'matching'; and continuing limited cultural
      understanding among care workers. The collaborative workshops identified
      practical actions that could address some of the issues identified. These covered
      raising awareness of services within communities; improving support for informal
      carers; service user input to assessments; consistent and ongoing sharing of
      information; improving access; and more efforts to diversify and appropriately
      train the social care workforce. In conclusion, the paper presents the reality of
      dissatisfaction among these groups and argues for more action involving
      communities and service providers to address these persistent issues
      collaboratively.

PMID- 27885739
TI  - ANALYSIS OF FACTORS AFFECTING OUTCOME OF ULTRASOUND-GUIDED RADIOFREQUENCY HEAT
      ABLATION FOR TREATMENT OF PRIMARY HYPERPARATHYROIDISM IN DOGS.
AB  - Radiofrequency (RF) parathyroid ablation is a noninvasive treatment for
      hyperparathyroidism in dogs. There are no published data assessing factors
      associated with RF parathyroid ablation success or failure in order to guide
      patient selection and improve outcome. The purpose of this retrospective
      analytical study was to determine whether imaging findings, biochemical data, or
      concurrent diseases were associated with RF heat ablation treatment failure. For
      inclusion in the study, dogs must have had a clinical diagnosis of primary
      hyperparathyroidism, undergone cervical ultrasound and RF ablation of abnormal
      parathyroid tissue, and must have had at least 3 months of follow-up information
      available following the date of ultrasound-guided parathyroid ablation. Dogs were
      grouped based on those with recurrent or persistent hypercalcemia and those
      without recurrent or persistent hypercalcemia following therapy. Parathyroid
      nodule size, thyroid lobe size, nodule location, and presence of concurrent
      disease were recorded. Recurrence of hypercalcemia occurred in 9/32 dogs that had
      ablation of abnormal parathyroid tissue (28%) and one patient had persistent
      hypercalcemia (3%) following parathyroid ablation. Nodule width (P = 0.036),
      height (P = 0.028), and largest cross-sectional area (P = 0.023) were larger in
      dogs that had recurrent or persistent hypercalcemia following ablation.
      Hypothyroidism was more common in dogs with recurrent disease (P = 0.044).
      Radiofrequency ablation was successful in 22/32 (69%) dogs. Larger parathyroid
      nodule size and/or concurrent hypothyroidism were associated with treatment
      failure in dogs that underwent ultrasound-guided RF parathyroid nodule ablation.

PMID- 27885741
TI  - Zika and pregnancy: A comprehensive review.
AB  - Zika virus (ZIKV) infection is a well-nurtured topic for healthcare personnel
      nowadays. Central nervous system involvement including microcephaly and ocular
      involvements has already been reported in neonates of affected pregnant ladies.
      In this article, we have discussed these effects on the newborns of ZIKV-infected
      mothers. The proposed pathogenesis, modes of transmission of this infection from
      mothers to the fetuses, diagnosis of the cases and precaution for the pregnant
      ladies have also been discussed. We have gathered the recently available data on
      the risk of ZIKV for expectant mothers from PubMed,
      https://www.gov.uk/guidance/zika-virus as well as from centers for disease
      control and prevention websites.

PMID- 27885742
TI  - Catheter Ablation in the Right Ventricular Outflow Tract Associated With
      Occlusion of Left Anterior Descending Coronary Artery.
AB  - Major vessel injury during right ventricular outflow tract ablation is not
      something widely recognized, and routine evaluation of the left anterior
      descending (LAD) artery location in relation to the septal right ventricle is not
      routinely performed. In the present article, we report a case of acute LAD
      occlusion after right ventricular outflow tract ablation and then illustrate the
      intimately close relationship of the LAD artery to the anterior septal site of
      the RVOT (approximately 2-3 cm under the pulmonic valve), using a combination of
      intracardiac echocardiography and 3-dimensional electroanatomical mapping
      recorded during a second case, in order to specifically point to the area at
      risk.

PMID- 27885743
TI  - Influence of polymerisation method and type of fibre on fracture strength of
      endodontically treated teeth.
AB  - The aim of this study was to investigate (i) the effect of direct or indirect
      polymerisation of adhesive-impregnated ribbon fibre under 4-mm bulk-filled
      composites on fracture strength; (ii) to compare polyethylene ribbon fibre
      reinforcement composites with short fibre-reinforced composite; and (iii) the
      effectiveness of polyethylene ribbon fibre according to the restorative materials
      used (low-viscous bulk-fill composite, high-viscous flowable composite or
      conventional paste composite). Seventy molars were divided into seven groups;
      (groups 1-2) Ribbond-reinforced Surefil-SDR; (group 3) Ribbond-reinforced G
      Aenial Flo; (group 4) Ribbond-reinforced G Aenial Posterior; (group 5) short
      fibre-reinforced composite everX Posterior; (group 6) unfilled cavity; (group 7)
      intact teeth. Ribbond was adopted to cavity walls by impregnating an adhesive and
      using a flowable composite. In group 1, adhesive-impregnated Ribbond was
      polymerised directly using a light-curing-unit, and indirectly in group 2 under 4
      mm bulk-filled composite. Direct or indirect polymerisation of adhesive
      impregnated ribbon fibre under 4-mm bulk-filled composite did not change the
      fracture strength results. Polyethylene ribbon fibre-reinforced groups (groups 1
      4) and short fibre-reinforced composite group (group 5) displayed similar
      results. Polyethylene ribbon fibre can be used safely under 4-mm bulk-filled
      composites. Ribbond-reinforced low-viscous bulk-fill, high-viscous flowable, and
      conventional paste composite exhibited similar fracture strength results.

PMID- 27885740
TI  - ASP5878, a selective FGFR inhibitor, to treat FGFR3-dependent urothelial cancer
      with or without chemoresistance.
AB  - FGF/FGFR gene aberrations such as amplification, mutation and fusion are
      associated with many types of human cancers including urothelial cancer. FGFR
      kinase inhibitors are expected to be a targeted therapy for urothelial cancer
      harboring FGFR3 gene alternations. ASP5878, a selective inhibitor of FGFR1, 2, 3
      and 4 under clinical investigation, selectively inhibited cell proliferation of
      urothelial cancer cell lines harboring FGFR3 point mutation or fusion (UM-UC-14,
      RT-112, RT4 and SW 780) among 23 urothelial cancer cell lines. Furthermore,
      ASP5878 inhibited cell proliferation of adriamycin-resistant UM-UC-14 cell line
      harboring MDR1 overexpression and gemcitabine-resistant RT-112 cell line. The
      protein expression of c-MYC, an oncoprotein, in gemcitabine-resistant RT-112 cell
      line was higher than that in RT-112 parental cell line and ASP5878 decreased the
      c-MYC expression in both RT-112 parental and gemcitabine-resistant RT-112 cell
      lines. Once-daily oral administration of ASP5878 exerted potent antitumor
      activities in UM-UC-14, RT-112 and gemcitabine-resistant RT-112 xenograft models
      without affecting body weight. These findings suggest that ASP5878 has the
      potential to be an oral targeted therapy against urothelial cancer harboring
      FGFR3 fusion or FGFR3 point mutation after the acquisition of gemcitabine- or
      adriamycin-resistance.

PMID- 27885744
TI  - Glutathione in combination with trehalose has supplementary beneficial effects on
      cryopreserved red deer (cervus elaphus) sperm.
AB  - OBJECTIVES: In this study, we evaluated the effects of glutathione in combination
      with trehalose addition to semen extenders on the quality parameters of frozen
      thawed red deer (cervus elaphus) spermatozoa. METHOD OF STUDY: The semen samples
      collected from six mature red deer once a week were diluted with Tris-egg yolk
      based extenders. The diluted semen samples were supplemented with glutathione (8
      mmol L-1 ) and or trehalose (5%, w/v), cryopreserved, thawed and then subjected
      to sperm quality parameter evaluation. RESULTS: Both glutathione and trehalose
      addition to the extender significantly improved progressive motility, acrosome
      integrity, membrane integrity, superoxide dismutase and glutathione peroxidase
      activity and decreased percentage abnormality and sperm malondialdehyde level
      compared with the control group (P<.05). Moreover, glutathione in combination
      with trehalose addition to semen extenders had higher efficiency compared with
      the glutathione or trehalose addition alone (P<.05). CONCLUSION: Therefore,
      glutathione in combination with trehalose could be a promising cryoprotectant for
      red deer sperm.

PMID- 27885745
TI  - Exaggerated Reactivity of Parasympathetic Nerves Is Involved in Ventricular
      Fibrillation in J-Wave Syndrome.
AB  - INTRODUCTION: Brugada syndrome (BrS) and early repolarization syndrome (ERS) are
      termed the J-wave syndrome. In most cases of J-wave syndrome, ventricular
      fibrillation (VF) often occurs around midnight or in the early morning when
      parasympathetic tone is augmented. OBJECTIVE: The purpose of this study was to
      clarify the relationship between VF and autonomic nervous activity in patients
      with J-wave syndrome. METHODS AND RESULTS: We enrolled 28 consecutive patients
      with J-wave syndrome (20 BrS and 8 ERS) in whom implantable cardioverter
      defibrillators (ICDs) were implanted between January 2002 and December 2014.
      Eleven patients (39%) experienced ICD shock delivery due to VF recurrence after
      ICD implantation (recurrent-VF group). We investigated baroreflex sensitivity
      (BRS) using the phenylephrine method, heart rate variability (HRV) with Holter
      electrocardiography, plasma levels of norepinephrine, and cardiac 123 I
      metaiodobenzylguanidine (MIBG) scintigraphy to estimate autonomic nervous
      function. Upon measurement of HRV, plasma levels of norepinephrine, and 123 I
      MIBG testing, there was no significant difference between recurrent-VF and
      nonrecurrent-VF groups. However, BRS was significantly higher in the recurrent-VF
      group than in the nonrecurrent-VF group (P = 0.03). Kaplan-Meier curves suggested
      that high-BRS patients had higher VF recurrence than those with nonhigh-BRS (P =
      0.04). Cox proportional hazards regression analyses showed that high BRS was
      associated independently with VF recurrence (P = 0.002). CONCLUSIONS: Our results
      suggest that exaggerated reactivity of parasympathetic nerves, as represented by
      increased BRS, may underlie VF in patients with J-wave syndrome.

PMID- 27885746
TI  - Group therapy processes and treatment outcomes in 2 couple-focused group
      interventions for breast cancer patients.
AB  - BACKGROUND: There has been little attention paid to the role of therapeutic
      processes in group therapy outcomes for cancer patients participating in group.
      The goal was to evaluate the contribution of 3 group processes-group climate
      (conflict, engagement, and avoidance) working alliance and therapeutic
      realizations-to the outcomes of 2 couple-focused approaches to group treatment.
      METHODS: Three hundred and two women with early stage breast cancer and their
      partners were randomized to one of 2 conditions: an 8-session enhanced couple
      focused group (ECG) intervention or a couples' support group participated.
      Couples completed measures of depressive symptoms and well-being before and 6
      months after group. Group process measures were completed after sessions 4 and 8.
      RESULTS: Support group participants (both patients and partners) perceived higher
      engagement and less avoidance than ECG participants. Conflict, working alliance,
      and therapeutic realizations did not differ. Group engagement, working alliance,
      and therapeutic realizations increased, and group conflict decreased over the
      course of both treatments. Greater conflict was associated with more
      posttreatment anxiety and lower well-being, and engagement was associated with
      higher posttreatment well-being. Patients whose partners reported higher conflict
      reported greater posttreatment anxiety. Working alliance was associated with
      posttreatment anxiety for ECG patients and with well-being among participants
      whose partners reported higher working alliance. CONCLUSIONS: Fostering a
      positive group environment bolsters treatment efficacy for women with early stage
      breast cancer and their partners attending couple-focused groups. Facilitating
      the leader-member alliance bolsters treatment efficacy. Improving engagement with
      one member of a couple impacts the other member.

PMID- 27885747
TI  - Exploring the relationship between nursing hours per patient day and mortality
      rate of hospitalised patients in Taiwan.
AB  - AIM: To investigate the relationship between nursing hours per patient day and
      the inpatient mortality rate in Taiwan. BACKGROUND: Nursing hours per patient day
      has been associated with better patient outcomes. The literature is inconclusive
      on the relationship between nursing hours per patient day and the inpatient
      mortality rate, and no studies have yet examined this issue in Taiwan. METHODS: A
      retrospective longitudinal study analysed data from the 'Nursing Utilization of
      Resources, Staffing and Environment on Outcome Study: NURSE-outcome study'.
      Hierarchical regression estimated the relationship between nursing hours per
      patient day and in-hospital mortality rate after controlling for confounding
      variables. RESULTS: The mean nursing hours per patient day in Taiwan was 2.3,
      while the mean inpatient mortality rate was 0.73% higher nursing hours per
      patient day was associated with a lower inpatient mortality rate after
      controlling for confounding variables. The total explained variance of this study
      in inpatient mortality rate was 19.9%. Significant relationships to inpatient
      mortality were found in levels of hospitals, seasonal variation and nurses' work
      experience. CONCLUSION: Nursing hours per patient day affects the mortality rate
      among hospitalised patients in Taiwan. IMPLICATIONS FOR NURSING MANAGEMENT:
      According to the results, we suggested the government and managers in Taiwan
      double the nursing hours per patient day so that the inpatient mortality rate
      will decline by 1.1%. This might be the optimal nurse configuration that could
      provide a balance between cost-effectiveness and patient safety.

PMID- 27885748
TI  - Protective efficacy and hepatitis B virus clearance in mice enhanced by cell
      mediated immunity with novel prime-boost regimens.
AB  - In this study, anti-hepatitis B virus (HBV) immunity was evaluated in mice using
      several regimens of the HBV recombinant protein vaccine HBSS1 that expressed in
      CHO cells containing S (1-223 aa) and preS1 (21-47 aa) and recombinant adenovirus
      rAdSS1 vaccine. Further, the protective efficacy of these vaccine regimens was
      studied in a mouse model. High titres of antigen-specific antibodies and
      neutralizing activity were elicited in mice after vaccination. However, robust
      multi-antigen (preS1 and S)-specific cell-mediated immunity (CMI) was only
      detected in mice primed with HBSS1 and boosted with rAdSS1. Moreover, functional
      T-cell responses with high levels of cytokines and antigen-specific cytotoxic T
      cell responses (CD107a+ CD8+ ) were also detected in the mice. Rapid clearance of
      hepatitis B surface antigen and HBV DNA in blood and significantly decreased
      hepatitis B envelope antigen levels were observed in mice immunized with the
      heterogeneous prime-boost vaccine after hepatitis B virus challenge by
      hydrodynamic injection (HI) of pCS-HBV1.3. The clearance of HBV correlated well
      with antigen-specific CMI (Th1 and CTL responses) and cytokine profiles (IFN
      gamma, TNF-alpha, IL-2) elicited by vaccination. Taken together, our results
      might contribute to the development of new human HBV vaccines and a better
      understanding of the mechanisms underlying immune protection and clearance of
      hepatitis B virus infection.

PMID- 27885749
TI  - Biophysical Modeling to Determine the Optimization of Left Ventricular Pacing
      Site and AV/VV Delays in the Acute and Chronic Phase of Cardiac Resynchronization
      Therapy.
AB  - BACKGROUND: Cardiac anatomy and function adapt in response to chronic cardiac
      resynchronization therapy (CRT). The effects of these changes on the optimal left
      ventricle (LV) lead location and timing delay settings have yet to be fully
      explored. OBJECTIVE: To predict the effects of chronic CRT on the optimal LV lead
      location and device timing settings over time. METHODS: Biophysical computational
      cardiac models were generated for 3 patients, immediately post-implant (ACUTE)
      and after at least 6 months of CRT (CHRONIC). Optimal LV pacing area and device
      settings were predicted by pacing the ACUTE and CHRONIC models across the LV
      epicardium (49 sites each) with a range of 9 pacing settings and simulating the
      acute hemodynamic response (AHR) of the heart. RESULTS: There were statistically
      significant differences between the distribution of the AHR in the ACUTE and
      CHRONIC models (P < 0.0005 in all cases). The site delivering the maximal AHR
      shifted location between the ACUTE and CHRONIC models but provided a negligible
      improvement (<2%). The majority of the acute optimal LV pacing regions (76-100%)
      and device settings (76-91%) remained optimal chronically. CONCLUSION:
      Optimization of the LV pacing location and device settings were important at the
      time of implant, with a reduced benefit over time, where the majority of the
      acute optimal LV pacing region and device settings remained optimal with chronic
      CRT.

PMID- 27885750
TI  - They're NICE and Neat, but Are They Useful? A Grounded Theory of Clinical
      Psychologists' Beliefs About and Use of NICE Guidelines.
AB  - : Guidelines are ubiquitous but inconsistently used in UK mental health services.
      Clinical psychologists are often influential in guideline development and
      implementation, but opinion within the profession is divided. This study utilized
      grounded theory methodology to examine clinical psychologists' beliefs about and
      use of NICE guidelines. Eleven clinical psychologists working in the NHS were
      interviewed. The overall emerging theme was; NICE guidelines are considered to
      have benefits but to be fraught with dangers. Participants were concerned that
      guidelines can create an unhelpful illusion of neatness. They managed the tension
      between the helpful and unhelpful aspects of guidelines by relating to them in a
      flexible manner. The participants reported drawing on specialist skills such as
      idiosyncratic formulation and integration. However, due to the pressures and
      dominant discourses within services they tended to practice in ways that prevent
      these skills from being recognized. This led to fears that their professional
      identity was threatened, which impacted upon perceptions of the guidelines. To
      our knowledge, the theoretical framework presented in this paper is the first
      that attempts to explain why NICE guidelines are not consistently utilized in UK
      mental health services. The current need for services to demonstrate 'NICE
      compliance' may be leading to a perverse incentive for clinical psychologists in
      particular to do one thing but say another and for specialist skills to be
      obscured. If borne out by future studies, this represents a threat to continued
      quality improvement and also to the profession. Copyright (c) 2016 John Wiley &
      Sons, Ltd. KEY PRACTITIONER MESSAGE: Guidelines have many benefits, but the
      current pressure for services to be 'NICE compliant' may be having unintended
      negative as well as positive effects. Lack of implementation may be partly the
      result of active choice by clinicians concerned to use the full range of
      professional skills and to offer flexibility and choice to service users. The
      current context is creating a perverse incentive for clinicians to say one thing
      but do another. This is problematic for services and a potential threat to the
      profession of clinical psychology.

PMID- 27885751
TI  - Effect of PR Interval on Outcomes Following Cardiac Resynchronization Therapy: A
      Secondary Analysis of the COMPANION Trial.
AB  - BACKGROUND: Prolonged PR intervals may impair atrioventricular mechanical
      coupling and adversely affect cardiac performance. We hypothesize that patients
      with advanced systolic heart failure, wide QRS complexes, and prolonged PR
      intervals will have improved survival from CRT-D regardless of whether left
      bundle branch block (LBBB) or non-LBBB is present. METHODS AND RESULTS: A total
      of 308 patients enrolled in the optimal pharmacologic therapy (OPT) and 595
      patients in the cardiac resynchronization therapy with defibrillation (CRT-D)
      arms of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart
      Failure trial were stratified according to normal (<=230 ms) or prolonged PR
      interval (>230 ms). The incidence of all-cause mortality (ACM) or hospitalization
      (primary endpoint) and ACM (secondary endpoint) was compared using Kaplan-Meier
      curves. Cox proportional hazards models for the primary and secondary endpoints
      were fit with LBBB status and baseline PR interval. CRT-D treatment reduced both
      hospitalization/ACM (P = 0.002) and ACM (P = 0.003) compared to OPT. However, CRT
      D was increasingly more effective in reducing ACM hazard in patients with longer
      baseline PR intervals (P = 0.002) regardless of LBBB status. In particular, in
      the prolonged baseline PR interval subgroup, ACM was reduced with CRT-D compared
      to OPT (P = 0.001) with little evidence of ACM reduction in the normal PR
      subgroup (P = 0.07). CONCLUSIONS: In patients with advanced systolic heart
      failure, wide QRS complexes, and prolonged PR intervals, restoration of
      atrioventricular mechanical coupling with CRT-D may improve survival regardless
      of LBBB status. In patients with non-LBBB, a benefit from CRT-D may occur with
      prolonged PR intervals.

PMID- 27885752
TI  - Biventricular Paced QRS Area Predicts Acute Hemodynamic CRT Response Better Than
      QRS Duration or QRS Amplitudes.
AB  - INTRODUCTION: Vectorcardiographic (VCG) QRS area of left bundle branch block
      (LBBB) predicts acute hemodynamic response in cardiac resynchronization therapy
      (CRT) patients. We hypothesized that changes in QRS area occurring with
      biventricular pacing (BV) might predict acute hemodynamic CRT response (AHR).
      METHODS AND RESULTS: VCGs of 624 BV paced electrocardiograms (25 LBBB patients
      with 35 different pacing configurations) were calculated according to Frank's
      orthogonal lead system. Maximum QRS vector amplitudes (XAmpl , YAmpl , ZAmpl ,
      and 3DAmp ) and QRS areas (XArea , YArea , ZArea , and 3DArea ) in the orthogonal
      leads (X, Y, and Z) and in 3-dimensional projection were measured. Volume of the
      3D vector loop and global QRS duration (QRSD) on the surface electrocardiogram
      were assessed. Differences (Delta) in VCG parameters between BV paced and LBBB
      QRS complexes were calculated. An increase of 10% in dP/dt max was considered as
      AHR. LBBB conduction is characterized by a large ZArea (109 MUVs, interquartile
      range [IQR]:75;135), significantly larger than XArea (22 MUVs, IQR:10;57) and
      YArea (44 MUVs, IQR:32;62, P < 0.001). Overall, QRS duration, amplitudes, and
      areas decrease significantly with BV pacing (P < 0.001). Of all VCG parameters,
      3DAmpl , Delta3DAmpl , ZArea, DeltaZArea , Delta3DArea , and DeltaQRSD
      differentiate AHR response from nonresponse (P < 0.05). DeltaZArea predicted best
      positive AHR (area under the curve = 0.813) and outperformed any other VCG
      parameter or QRSD measurement. CONCLUSION: Of all VCG parameters, reduction in
      QRS area, calculated in Frank's Z lead, predicts acute hemodynamic response best.
      This method might be an easy, noninvasive tool to guide CRT implantation and
      optimization.

PMID- 27885753
TI  - Prognosis of 1169 hepatitis C chronically infected patients with decompensated
      cirrhosis in the predirect-acting antiviral era.
AB  - At a population level, little is known regarding the risk of liver- and nonliver
      related mortality and hospitalization and the development of hepatocellular
      carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated
      cirrhosis (DC). This large-scale national record-linkage study estimates these
      outcomes following first hospital admission for DC. Record-linkages between
      national HCV diagnosis and clinical databases and the national inpatient hospital
      episode database and mortality register were conducted to follow-up the disease
      course of all identified HCV-diagnosed and chronically infected persons. The
      study population consisted of 1169 HCV chronically infected persons who had a
      first hospital admission for DC within the period 1994-2013. We observed an
      overall average annual percentage change of 12.6% in new DC patients (from 63 in
      1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the
      relative risks of liver-related or all-cause death over time. Between 1 January
      1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver
      related cause, respectively, and 106 patients had a subsequent first admission
      for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver
      related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%,
      respectively. The health burden in HCV-infected patients associated with
      development of decompensated cirrhosis has increased dramatically over the last
      20 years. Our findings establish the baseline mortality and HCC progression rates
      in DC patients against which the impact of new antiviral therapies can be
      measured.

PMID- 27885754
TI  - Adaptive and plastic responses of Quercus petraea populations to climate across
      Europe.
AB  - How temperate forests will respond to climate change is uncertain; projections
      range from severe decline to increased growth. We conducted field tests of
      sessile oak (Quercus petraea), a widespread keystone European forest tree
      species, including more than 150 000 trees sourced from 116 geographically
      diverse populations. The tests were planted on 23 field sites in six European
      countries, in order to expose them to a wide range of climates, including sites
      reflecting future warmer and drier climates. By assessing tree height and
      survival, our objectives were twofold: (i) to identify the source of differential
      population responses to climate (genetic differentiation due to past divergent
      climatic selection vs. plastic responses to ongoing climate change) and (ii) to
      explore which climatic variables (temperature or precipitation) trigger the
      population responses. Tree growth and survival were modeled for contemporary
      climate and then projected using data from four regional climate models for years
      2071-2100, using two greenhouse gas concentration trajectory scenarios each.
      Overall, results indicated a moderate response of tree height and survival to
      climate variation, with changes in dryness (either annual or during the growing
      season) explaining the major part of the response. While, on average, populations
      exhibited local adaptation, there was significant clinal population
      differentiation for height growth with winter temperature at the site of origin.
      The most moderate climate model (HIRHAM5-EC; rcp4.5) predicted minor decreases in
      height and survival, while the most extreme model (CCLM4-GEM2-ES; rcp8.5)
      predicted large decreases in survival and growth for southern and southeastern
      edge populations (Hungary and Turkey). Other nonmarginal populations with
      continental climates were predicted to be severely and negatively affected
      (Berce, France), while populations at the contemporary northern limit (colder and
      humid maritime regions; Denmark and Norway) will probably not show large changes
      in growth and survival in response to climate change.

PMID- 27885755
TI  - Marine assemblages respond rapidly to winter climate variability.
AB  - Even species within the same assemblage have varied responses to climate change,
      and there is a poor understanding for why some taxa are more sensitive to climate
      than others. In addition, multiple mechanisms can drive species' responses, and
      responses may be specific to certain life stages or times of year. To test how
      marine species respond to climate variability, we analyzed 73 diverse taxa off
      the southeast US coast in 26 years of scientific trawl survey data and determined
      how changes in distribution and biomass relate to temperature. We found that
      winter temperatures were particularly useful for explaining interannual variation
      in species' distribution and biomass, although the direction and magnitude of the
      response varied among species from strongly negative, to little response, to
      strongly positive. Across species, the response to winter temperature varied
      greatly, with much of this variation being explained by thermal preference. A
      separate analysis of annual commercial fishery landings revealed that winter
      temperatures may also impact several important fisheries in the southeast United
      States. Based on the life stages of the species surveyed, winter temperature
      appears to act through overwinter mortality of juveniles or as a cue for
      migration timing. We predict that this assemblage will be responsive to projected
      increases in temperature and that winter temperature may be broadly important for
      species relationships with climate on a global scale.

PMID- 27885756
TI  - Structure of Monomeric Transthyretin Carrying the Clinically Important T119M
      Mutation.
AB  - Mutations in the protein transthyretin can cause as well as protect individuals
      from transthyretin amyloidosis, an incurable fatal inherited disease. Little is
      known, however, about the structural basis of pathogenic and clinically
      protective transthyretin mutants. Here we determined the solution structure of a
      transthyretin monomer that carries the clinically important T119M mutation. The
      structure displays a non-native arrangement that is distinct from all known
      structures of transthyretin and highlights the importance of high-resolution
      studies in solution for understanding molecular processes that lead to amyloid
      diseases.

PMID- 27885757
TI  - Role of primary T-cell immunodeficiency and hepatitis B coinfection on
      spontaneous clearance of hepatitis C: The BC Hepatitis Testers Cohort.
AB  - T-cell host immune response against hepatitis C virus (HCV) has been suggested to
      play an important role in determining HCV infection outcome. However, data from
      human studies are not available. This study examined the effect of primary T-cell
      deficiency along with other factors on the spontaneous clearance of HCV in a
      large population-based cohort in British Columbia, Canada. The BC Hepatitis
      Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked
      with data on their medical visits, hospitalizations and prescription drugs. HCV
      positive individuals with at least one valid HCV PCR test on/after HCV diagnosis
      (n=46 783) were included in this study. To examine factors associated with the
      spontaneous clearance of HCV, multivariable logistic regression was fitted on the
      full sample, and Cox proportional hazards model on the HCV seroconverters.
      Spontaneous clearance was observed in 25.1% (n=11 737) of those tested for HCV.
      After adjusting for potential confounders, the odds of spontaneous clearance of
      HCV was lower in people with primary T-cell immunodeficiency (adjusted odds ratio
      [aOR]: 0.55, 95% CI: 0.32-0.94), and higher in females (aOR: 1.61, 95% CI: 1.54
      1.68) and in those coinfected with HBV (aOR: 2.31, 95% CI: 1.93-2.77). Similar
      results were observed in HCV seroconverters except HBV coinfection was not
      significant. In conclusion, primary T-cell immunodeficiency is associated with a
      lower spontaneous clearance of HCV while female sex and coinfection with HBV are
      associated with a higher spontaneous clearance.

PMID- 27885758
TI  - Cost-Effective, High-Performance Porous-Organic-Polymer Conductors Functionalized
      with Sulfonic Acid Groups by Direct Postsynthetic Substitution.
AB  - We demonstrate the facile microwave-assisted synthesis of a porous organic
      framework 1 and the sulfonated solid (1S) through postsubstitution. Remarkably,
      the conductivity of 1S showed an approximately 300-fold enhancement at 30 
      degrees C as compared to that of 1, and reached 7.72*10-2  S cm-1 at 80  degrees
      C and 90 % relative humidity. The superprotonic conductivity exceeds that
      observed for any conductive porous organic polymer reported to date. This
      material, which is cost-effective and scalable for mass production, also revealed
      long-term performance over more than 3 months without conductivity decay.

PMID- 27885759
TI  - Transanal minimally invasive rectal resection for deep endometriosis: a promising
      technique.
AB  - AIM: Surgical management of patients with deep endometriosis (DE) of the rectum
      is difficult. Inflammation and subsequent adhesions due to DE impede access to
      the lower pelvis and may lead to complications during laparoscopic low anterior
      resection (LAR). Transanal minimally invasive surgery (TAMIS) is an alternative
      to an abdominal approach with potential advantages. The aim of this study was to
      provide a description of the TAMIS technique and to present the perioperative
      results of TAMIS and of conventional LAR in patients with DE. METHOD: A
      prospective consecutive cohort of patients undergoing rectal resection for DE had
      either conventional laparoscopic LAR or TAMIS rectal excision. Pre-, intra- and
      postoperative parameters, such as patient symptomatology, operating time and
      postoperative complications were compared between the groups. Quality of life was
      assessed using the EORTC-QLQ-29/30 questionnaires. RESULTS: Between May 2014 and
      March 2016 a total of 11 rectal resections were performed, including five TAMIS
      procedures. No differences were found in the pre-, intra- or postoperative
      parameters. Two major complications occurred after conventional LAR and none
      after TAMIS. No differences in quality of life were found between the groups.
      CONCLUSION: Transanal minimally invasive surgery for DE of the rectum is
      feasible. Potential advantages include better surgical access to the pelvis,
      possibly fewer complications than LAR and no extraction incision with no
      difference in quality of life. Larger prospective studies are required to compare
      TAMIS with conventional rectal resection.

PMID- 27885760
TI  - Haploidentical hematopoietic stem cell transplantation for a case with X-linked
      chronic granulomatous disease.
AB  - CGD is a rare primary immunodeficiency with high mortality rates when treated
      conventionally, especially for the X-chromosome-linked form. HSCT is the only
      curative therapy for CGD; however, haploidentical transplantation in CGD is rare.
      Here, we report a case of X-linked CGD treated successfully by haploidentical
      HSCT. The patient showed a positive result with full donor chimerism, good
      quality of life, and the absence of recurrent infectious diseases at follow-up
      (68 months). Thus, haploidentical HSCT may serve as an acceptable treatment
      approach for patients who have CGD, but no HLA-matched related or unrelated
      donor.

PMID- 27885761
TI  - A Stably Protonated Adenine Nucleotide with a Highly Shifted pKa Value Stabilizes
      the Tertiary Structure of a GTP-Binding RNA Aptamer.
AB  - RNA tertiary structure motifs are stabilized by a wide variety of hydrogen
      bonding interactions. Protonated A and C nucleotides are normally not considered
      to be suitable building blocks for such motifs since their pKa values are far
      from physiological pH. Here, we report the NMR solution structure of an in vitro
      selected GTP-binding RNA aptamer bound to GTP with an intricate tertiary
      structure. It contains a novel kind of base quartet stabilized by a protonated A
      residue. Owing to its unique structural environment in the base quartet, the pKa
      value for the protonation of this A residue in the complex is shifted by more
      than 5 pH units compared to the pKa for A nucleotides in single-stranded RNA.
      This is the largest pKa shift for an A residue in structured nucleic acids
      reported so far, and similar in size to the largest pKa shifts observed for amino
      acid side chains in proteins. Both RNA pre-folding and ligand binding contribute
      to the pKa shift.

PMID- 27885762
TI  - Esophageal tuberculosis with coexisting opportunistic infections in a renal
      allograft transplant recipient.
AB  - We report a renal allograft transplant recipient with esophageal tuberculosis
      (TB) coinfected with herpes simplex virus (HSV) and Candida. The patient
      presented with oropharyngeal candidiasis and was started on fluconazole. Upper
      gastrointestinal endoscopy showed whitish patches with mucosal ulcers in the
      esophagus. Histopathological examination confirmed TB and HSV infection. The
      patient recovered after antiviral, antifungal, and anti-tubercular therapy with
      reduction in immunosuppression. In a TB-endemic zone, TB can coexist with
      opportunistic infections in an immunocompromised host.

PMID- 27885763
TI  - Meditation awareness training for the treatment of fibromyalgia syndrome: A
      randomized controlled trial.
AB  - OBJECTIVES: The purpose of this study was to conduct the first randomized
      controlled trial (RCT) to evaluate the effectiveness of a second-generation
      mindfulness-based intervention (SG-MBI) for treating fibromyalgia syndrome (FMS).
      Compared to first-generation mindfulness-based interventions, SG-MBIs are more
      acknowledging of the spiritual aspect of mindfulness. DESIGN: A RCT employing
      intent-to-treat analysis. METHODS: Adults with FMS received an 8-week SG-MBI
      known as meditation awareness training (MAT; n = 74) or an active control
      intervention known as cognitive behaviour theory for groups (n = 74). Assessments
      were performed at pre-, post-, and 6-month follow-up phases. RESULTS: Meditation
      awareness training participants demonstrated significant and sustained
      improvements over control group participants in FMS symptomatology, pain
      perception, sleep quality, psychological distress, non-attachment (to self,
      symptoms, and environment), and civic engagement. A mediation analysis found that
      (1) civic engagement partially mediated treatment effects for all outcome
      variables, (2) non-attachment partially mediated treatment effects for
      psychological distress and sleep quality, and (3) non-attachment almost fully
      mediated treatment effects for FMS symptomatology and pain perception. Average
      daily time spent in meditation was found to be a significant predictor of changes
      in all outcome variables. CONCLUSIONS: Meditation awareness training may be a
      suitable treatment for adults with FMS and appears to ameliorate FMS
      symptomatology and pain perception by reducing attachment to self. Statement of
      contribution What is already known on this subject? Designing interventions to
      treat fibromyalgia syndrome (FMS) continues to be a challenge. There is growing
      interest into the applications of mindfulness-based interventions for treating
      FMS. Second-generation mindfulness-based interventions (SG-MBIs) are a key new
      direction in mindfulness research. What does this study add? Meditation awareness
      training - an SG-MBI - resulted in significant reductions in FMS symptomatology.
      SG-MBIs recognize the spiritual aspect of mindfulness and may have a role in the
      treatment of FMS.

PMID- 27885764
TI  - Development of rubber-enriched dandelion varieties by metabolic engineering of
      the inulin pathway.
AB  - Natural rubber (NR) is an important raw material for a large number of industrial
      products. The primary source of NR is the rubber tree Hevea brasiliensis, but
      increased worldwide demand means that alternative sustainable sources are
      urgently required. The Russian dandelion (Taraxacum koksaghyz Rodin) is such an
      alternative because large amounts of NR are produced in its root system. However,
      rubber biosynthesis must be improved to develop T. koksaghyz into a commercially
      feasible crop. In addition to NR, T. koksaghyz also produces large amounts of the
      reserve carbohydrate inulin, which is stored in parenchymal root cell vacuoles
      near the phloem, adjacent to apoplastically separated laticifers. In contrast to
      NR, which accumulates throughout the year even during dormancy, inulin is
      synthesized during the summer and is degraded from the autumn onwards when root
      tissues undergo a sink-to-source transition. We carried out a comprehensive
      analysis of inulin and NR metabolism in T. koksaghyz and its close relative T.
      brevicorniculatum and functionally characterized the key enzyme fructan 1
      exohydrolase (1-FEH), which catalyses the degradation of inulin to fructose and
      sucrose. The constitutive overexpression of Tk1-FEH almost doubled the rubber
      content in the roots of two dandelion species without any trade-offs in terms of
      plant fitness. To our knowledge, this is the first study showing that energy
      supplied by the reserve carbohydrate inulin can be used to promote the synthesis
      of NR in dandelions, providing a basis for the breeding of rubber-enriched
      varieties for industrial rubber production.

PMID- 27885765
TI  - Conversion of the Native 24-mer Ferritin Nanocage into Its Non-Native 16-mer
      Analogue by Insertion of Extra Amino Acid Residues.
AB  - Protein assemblies with high symmetry are widely distributed in nature. Most
      efforts so far have focused on repurposing these protein assemblies, a strategy
      that is ultimately limited by the structures available. To overcome this
      limitation, methods for fabricating novel self-assembling proteins have received
      intensive interest. Herein, by reengineering the key subunit interfaces of native
      24-mer protein cage with octahedral symmetry through amino acid residues
      insertion, we fabricated a 16-mer lenticular nanocage whose structure is unique
      among all known protein cages. This newly non-native protein can be used for
      encapsulation of bioactive compounds and exhibits high uptake efficiency by
      cancer cells. More importantly, the above strategy could be applied to other
      naturally occurring protein assemblies with high symmetry, leading to the
      generation of new proteins with unexplored functions.

PMID- 27885766
TI  - Crystal Structure Determination of the Pentagonal-Pyramidal Hexamethylbenzene
      Dication C6 (CH3 )62.
AB  - In contrast to the well-known 2-norbornyl cation, the structure of which was a
      matter of long debate until its pentacoordinated nature was recently proven by an
      X-ray structure, the pentagonal-pyramidal dication of hexamethylbenzene has
      received considerably less attention. This species was first prepared by Hogeveen
      in 1973 at low temperatures in magic acid (HSO3 F/SbF5 ), for which he proposed a
      non-classical structure (containing a hexacoordinated carbon) based on NMR
      spectroscopy and reactivity studies, but no X-ray crystal structure has been
      reported. C6 (CH3 )62+ can be obtained through the dissolution of hexamethyl
      Dewar benzene epoxide in HSO3 F/SbF5 and crystallized as the SbF6- salt upon
      addition of excess anhydrous hydrogen fluoride. The crystal structure of C6 (CH3
      )62+ (SbF6- )2 ?HSO3 F confirms the pentagonal pyramidal structure of the
      dication. The apical carbon is bound to one methyl group (distance 1.479(3) A)
      and to the five basal carbon atoms (distances 1.694(2)-1.715(3) A).

PMID- 27885767
TI  - New Amino-Acid-Based beta-Phosphorylated Nitroxides for Probing Acidic pH in
      Biological Systems by EPR Spectroscopy.
AB  - There is increasing interest in measuring pH in biological samples by using
      nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra.
      Aiming to improve the spectral sensitivity (DeltaaX ) of these probes (i.e., the
      difference between the EPR hyperfine splitting (hfs) in their protonated and
      unprotonated forms), we characterized a series of novel linear alpha-carboxy,
      alpha'-diethoxyphosphoryl nitroxides constructed on an amino acid core and
      featuring an (alpha or alpha')-C-H bond. In buffer, the three main hfs (aN , aH ,
      and aP ) of their EPR spectra vary reversibly with pH and, from aP or aH
      titration curves, a two- to fourfold increase in sensitivity was achieved
      compared to reference imidazoline or imidazolidine nitroxides. The crystallized
      carboxylate 10 b (pKa ~3.6), which demonstrated low cytotoxicity and good
      resistance to bioreduction, was applied to probe stomach acidity in rats. The
      results pave the way to a novel generation of highly sensitive EPR pH markers.

PMID- 27885768
TI  - Gram-Scale Synthesis of Chiral Cyclopropane-Containing Drugs and Drug Precursors
      with Engineered Myoglobin Catalysts Featuring Complementary Stereoselectivity.
AB  - Engineered hemoproteins have recently emerged as promising systems for promoting
      asymmetric cyclopropanations, but variants featuring predictable, complementary
      stereoselectivity in these reactions have remained elusive. In this study, a
      rationally driven strategy was implemented and applied to engineer myoglobin
      variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high
      trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these
      cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective
      variants developed here and previously. In combination with whole-cell
      biotransformations, these stereocomplementary biocatalysts enabled the multigram
      synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine,
      Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent
      diastereo- and enantioselectivity (98-99.9% de; 96-99.9% ee). These biocatalytic
      strategies outperform currently available methods to produce these drugs.

PMID- 27885769
TI  - Diverging shrub and tree growth from the Polar to the Mediterranean biomes across
      the European continent.
AB  - Climate warming is expected to enhance productivity and growth of woody plants,
      particularly in temperature-limited environments at the northernmost or uppermost
      limits of their distribution. However, this warming is spatially uneven and
      temporally variable, and the rise in temperatures differently affects biomes and
      growth forms. Here, applying a dendroecological approach with generalized
      additive mixed models, we analysed how the growth of shrubby junipers and
      coexisting trees (larch and pine species) responds to rising temperatures along a
      5000-km latitudinal range including sites from the Polar, Alpine to the
      Mediterranean biomes. We hypothesize that, being more coupled to ground
      microclimate, junipers will be less influenced by atmospheric conditions and will
      less respond to the post-1950 climate warming than coexisting standing trees.
      Unexpectedly, shrub and tree growth forms revealed divergent growth trends in all
      the three biomes, with juniper performing better than trees at Mediterranean than
      at Polar and Alpine sites. The post-1980s decline of tree growth in Mediterranean
      sites might be induced by drought stress amplified by climate warming and did not
      affect junipers. We conclude that different but coexisting long-living growth
      forms can respond differently to the same climate factor and that, even in
      temperature-limited area, other drivers like the duration of snow cover might
      locally play a fundamental role on woody plants growth across Europe.

PMID- 27885770
TI  - The power of symbolic capital in patient and public involvement in health
      research.
AB  - BACKGROUND: Policy-makers and health research funders increasingly require
      researchers to demonstrate that they have involved patients in the design and
      conduct of research. However, the extent to which patients and public have the
      power to get involved on an equal footing is dependent on their economic,
      cultural, social and symbolic capital. OBJECTIVE: To explore power relations in
      patient and public involvement (PPI) in research, particularly how patients may
      wield symbolic capital to develop a more equal relationship. METHODS: Narrative
      interviews with a maximum variation sample of 38 people involved as patients,
      carers or public in health research, analysed thematically. FINDINGS: Symbolic
      capital may be demonstrated in a range of ways (sometimes alongside or in the
      absence of other forms of capital): illness experience, technical illness
      knowledge and the challenging outsider. Symbolic capital is unstable and
      dependent on others for recognition and legitimacy. Nonetheless, participants
      identify a gradual shift in power relations over time. DISCUSSION AND
      CONCLUSIONS: Research into PPI has been conceptually and theoretically poor,
      limiting our understanding of its mechanisms and wider contextual elements. Our
      findings demonstrate the importance of reflecting on the forms of power and
      capital wielded by the health research community, and of acknowledging the way in
      which PPI is challenging the status quo. As one of the first papers to
      conceptualize how different forms of symbolic capital operate and their critical
      role in challenging the balance of power, our findings may help researchers
      better plan their PPI activities and reflect on their own power.

PMID- 27885774
TI  - CORRIGENDUM.

PMID- 27885771
TI  - Selective gene dosage by CRISPR-Cas9 genome editing in hexaploid Camelina sativa.
AB  - In many plant species, gene dosage is an important cause of phenotype variation.
      Engineering gene dosage, particularly in polyploid genomes, would provide an
      efficient tool for plant breeding. The hexaploid oilseed crop Camelina sativa,
      which has three closely related expressed subgenomes, is an ideal species for
      investigation of the possibility of creating a large collection of combinatorial
      mutants. Selective, targeted mutagenesis of the three delta-12-desaturase (FAD2)
      genes was achieved by CRISPR-Cas9 gene editing, leading to reduced levels of
      polyunsaturated fatty acids and increased accumulation of oleic acid in the oil.
      Analysis of mutations over four generations demonstrated the presence of a large
      variety of heritable mutations in the three isologous CsFAD2 genes. The different
      combinations of single, double and triple mutants in the T3 generation were
      isolated, and the complete loss-of-function mutants revealed the importance of
      delta-12-desaturation for Camelina development. Combinatorial association of
      different alleles for the three FAD2 loci provided a large diversity of Camelina
      lines with various lipid profiles, ranging from 10% to 62% oleic acid
      accumulation in the oil. The different allelic combinations allowed an unbiased
      analysis of gene dosage and function in this hexaploid species, but also provided
      a unique source of genetic variability for plant breeding.

PMID- 27885772
TI  - Clinical practice patterns on the use of magnesium sulphate for treatment of pre
      eclampsia and eclampsia: a multi-country survey.
AB  - OBJECTIVE: To characterise the current clinical practice patterns regarding the
      use of magnesium sulphate (MgSO4 ) for eclampsia prevention and treatment in a
      multi-country network of health facilities and compare with international
      recommendations. DESIGN: Cross-sectional survey. SETTING: A total of 147 health
      facilities in 15 countries across Africa, Latin America and Asia. POPULATION:
      Heads of obstetric departments or maternity units. METHODS: Anonymous online and
      paper-based survey conducted in 2015. MAIN OUTCOME MEASURES: Availability and use
      of MgSO4 ; availability of a formal clinical protocol for MgSO4 administration;
      and MgSO4 dosing regimens for eclampsia prevention and treatment. RESULTS:
      Magnesium sulphate and a formal protocol for its administration were reported to
      be always available in 87.4% and 86.4% of all facilities, respectively. MgSO4 was
      used for the treatment of mild pre-eclampsia, severe pre-eclampsia and eclampsia
      in 24.3%, 93.5% and 96.4% of all facilities, respectively. Regarding the
      treatment of severe pre-eclampsia, 26.4% and 7.0% of all facilities reported
      using dosing regimens that were consistent with Zuspan and Pritchard regimens,
      respectively. Across regions, intramuscular maintenance regimens were more
      commonly used in the African region (45.7%) than in the Latin American (3.0%) and
      Asian (22.9%) regions, whereas intravenous maintenance regimens were more often
      used in the Latin American (94.0%) and Asian (60.0%) regions than in the African
      region (21.7%). Similar patterns were found for the treatment of eclampsia across
      regions. CONCLUSIONS: The reported clinical use of MgSO4 for eclampsia prevention
      and treatment varied widely, and was largely inconsistent with current
      international recommendations. TWEETABLE ABSTRACT: MgSO4 regimens for eclampsia
      prevention and treatment in many hospitals are inconsistent with international
      recommendations.

PMID- 27885775
TI  - The coffee leaf rust pathogen Hemileia vastatrix: one and a half centuries around
      the tropics.
AB  - TAXONOMY AND HISTORY: Hemileia vastatrix Berk. and Broome (Basidiomycota,
      Pucciniales) was described in 1869 in eastern Africa and Ceylon as the agent of
      coffee leaf rust and has spread to all coffee cultivation areas worldwide. Major
      disease outbreaks in Asia, Africa and America caused and continue to cause severe
      yield losses, making this the most important disease of Arabica coffee, a cash
      crop for many tropical and sub-tropical countries. LIFE CYCLE AND DISEASE
      SYMPTOMS: Hemileia vastatrix is a hemicyclic fungus with the urediniosporic life
      cycle as its most important (if not only) source of inoculum. Chlorotic spots are
      the first macroscopic symptoms, preceding the differentiation of suprastomatal,
      bouquet-shaped, orange-coloured uredinia. The disease can cause yield losses of
      up to 35% and have a polyetic epidemiological impact on subsequent years. DISEASE
      CONTROL: Although the use of fungicides is one of the preferred immediate control
      measures, the use of resistant cultivars is considered to be the most effective
      and durable disease control strategy. The discovery of 'Hibrido de Timor'
      provided sources of resistance that have been used in several breeding programmes
      and that have been proven to be effective and durable, as some have been in use
      for more than 30 years. GENETIC DIVERSITY AND MOLECULAR PATHOGENICITY: Although
      exhibiting limited genetic polymorphism, the very large genome of H. vastatrix
      (c. 797 Mbp) conceals great pathological diversity, with more than 50
      physiological races. Gene expression studies have revealed a very precocious
      activation of signalling pathways and production of putative effectors,
      suggesting that the plant-fungus dialogue starts as early as at the germ tube
      stage, and have provided clues for the identification of avr genes.

PMID- 27885776
TI  - Multidisciplinary care ensures successful pregnancy following intestinal
      transplantation: a case report.

PMID- 27885777
TI  - Variable Time Normalization Analysis: General Graphical Elucidation of Reaction
      Orders from Concentration Profiles.
AB  - The recent technological evolution of reaction monitoring techniques has not been
      paralleled by the development of modern kinetic analyses. The analyses currently
      used disregard part of the data acquired, thus requiring an increased number of
      experiments to obtain sufficient kinetic information for a given chemical
      reaction. Herein, we present a simple graphical analysis method that takes
      advantage of the data-rich results provided by modern reaction monitoring tools.
      This analysis uses a variable normalization of the time scale to enable the
      visual comparison of entire concentration reaction profiles. As a result, the
      order in each component of the reaction, as well as kobs  , is determined with
      just a few experiments using a simple and quick mathematical data treatment. This
      analysis facilitates the rapid extraction of relevant kinetic information and
      will be a valuable tool for the study of reaction mechanisms.

PMID- 27885778
TI  - Single dose versus multiple dose of antibiotic prophylaxis in caesarean section:
      a systematic review and meta-analysis.
AB  - BACKGROUND: Prophylactic antibiotics are traditionally given as a single dose for
      caesarean section. However, inconsistent application of recommendations and
      recent evidence prompted a literature review. OBJECTIVES: To assess the optimal
      regimen for antibiotic prophylaxis in caesarean section by comparing single
      versus multiple doses of the same intervention. SEARCH STRATEGY: MEDLINE, Web of
      Knowledge, SCOPUS, CENTRAL and ongoing trials databases were searched. Reference
      lists were reviewed and international groups contacted. SELECTION CRITERIA:
      Randomised controlled trials (RCT) comparing single with multiple dose regimens
      of the same antibiotic prophylaxis. Quasi-RCT and abstracts were suitable for
      inclusion. DATA COLLECTION AND ANALYSIS: Reviewers independently extracted data
      and assessed quality of evidence. A random-effects model was used and results
      presented as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS:
      Sixteen studies were included, involving 2695 women. Nonsignificant differences
      were observed between single dose and multiple dose antibiotic prophylaxis in the
      incidence of postpartum infectious morbidity (RR 0.95, 95% CI 0.75-1.20, I2 =
      25%), endometritis (RR 1.03, 95% CI 0.74-1.42, I2 = 0%) and wound infection (RR
      1.22, 95% CI 0.72-2.08, I2 = 0%). A trend towards lower risk of urinary tract
      infection was seen with multiple dose (RR 0.65, 95% CI 0.34-1.24, I2 = 0%).
      CONCLUSIONS: There was insufficient evidence to determine whether there is a
      difference between single and multiple dose regimens in reducing the incidence of
      infectious morbidity after caesarean section. The quality of evidence was very
      low and well-designed RCTs are needed. TWEETABLE ABSTRACT: Insufficient evidence
      of difference between dosage regimens of antibiotic prophylaxis in caesarean
      section.

PMID- 27885779
TI  - Explaining the Cyclic Voltammetry of a Poly(1,4-phenylene-ethynylene)-alt
      poly(1,4-phenylene-vinylene) Copolymer upon Oxidation by using Spectroscopic
      Techniques.
AB  - Poly(1,4-phenylene-ethynylene)-alt-poly(1,4-phenylene-vinylene) (PPE-PPV)
      copolymers have attracted quite a lot of attention in the last few years for
      electronic device applications owing to their enhanced fluorescence. In this
      work, we focus on one particular PPE-PPV copolymer with dissymmetrically
      substituted 1,4-phenylene-ethynylene and symmetrically substituted 1,4-phenylene
      vinylene building units. Six successively performed cyclic voltammograms are
      presented, measured during the oxidation reactions. As the oxidation onset of the
      electrochemical reaction shifts to lower potentials in each cycle, this behavior
      is elucidated by using spectroscopic techniques ranging from UV/Vis/near-IR to
      mid-IR including spin-resonance techniques. Hence, these findings help to explain
      some of the copolymer's most advantageous properties in terms of possible
      oxidation products.

PMID- 27885780
TI  - Synthesis and Investigation of Advanced Energetic Materials Based on
      Bispyrazolylmethanes.
AB  - Herein we present the preparation and characterization of three new bispyrazolyl
      based energetic compounds with great potential as explosive materials. The
      reaction of sodium 4-amino-3,5-dinitropyrazolate (5) with dimethyl iodide yielded
      bis(4-amino-3,5-dinitropyrazolyl)methane (6), which is a secondary explosive with
      high heat resistance (Tdec =310  degrees C). The oxidation of this compound
      afforded bis(3,4,5-trinitropyrazolyl)methane (7), which is a combined nitrogen-
      and oxygen-rich secondary explosive with very high theoretical and estimated
      experimental detonation performance (Vdet (theor)=9304 m s-1 versus Vdet
      (exp)=9910 m s-1 ) in the range of that of CL-20. Also, the thermal stability
      (Tdec =205  degrees C) and sensitivities of 7 are auspicious. The reaction of 6
      with in situ generated nitrous acid yielded the primary explosive bis(4-diazo-5
      nitro-3-oxopyrazolyl)methane (8), which showed superior properties to those of
      currently used diazodinitrophenol (DDNP).

PMID- 27885781
TI  - Cellular response of osteoblasts to low modulus Ti-24Nb-4Zr-8Sn alloy mesh
      structure.
AB  - Titanium alloys (Ti-6Al-4V and Ti-6Al-7Nb) are widely used for implants, which
      are characterized by high elastic modulus (~110 GPa) with (alpha + beta)
      structure and that may induce undesirable stress shielding effect and immune
      responses associated with the presence of toxic elements. In this regard, we have
      combined the attributes of a new alloy design and the concept of additive
      manufacturing to fabricate 3D scaffolds with an interconnected porous structure.
      The new alloy is a beta-type Ti-24Nb-4Zr-8Sn (Ti2448) alloy with significantly
      reduced modulus. In the present study, we explore the biological response of
      electron beam melted low modulus Ti2448 alloy porous mesh structure through the
      elucidation of bioactivity and osteoblast functions. The cellular activity was
      explored in terms of cell-to-cell communication involving proliferation,
      spreading, synthesis of extracellular and intracellular proteins,
      differentiation, and mineralization. The formation of fine apatite-like crystals
      on the surface during immersion test in simulated body fluid confirmed the
      bioactivity of the scaffold surface, which provided the favorable osteogenic
      microenvironment for cell-material interaction. The combination of unique surface
      chemistry and interconnected porous architecture provided the desired pathway for
      supply of nutrients and oxygen to cells and a favorable osteogenic micro
      environment for incorporation (on-growth and in-growth) of osteoblasts. The
      proliferation and differentiation of pre-osteoblasts and their ability to form a
      well mineralized bone-like extracellular matrix (ECM) by secreting bone markers
      (ALP, calcium, etc.) over the struts of the scaffold point toward the determining
      role of unique surface chemistry and 3D architecture of the Ti2448 alloy mesh
      structure in modulating osteoblasts functions. (c) 2016 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 105A: 859-870, 2017.

PMID- 27885782
TI  - Field evaluation of 3-hydroxy-2-hexanone and ethanol as attractants for the
      cerambycid beetle pest of vineyards, Xylotrechus arvicola.
AB  - BACKGROUND: The beetle Xylotrechus arvicola (Coleoptera: Cerambycidae) is a
      serious pest of vineyards in the Iberian Peninsula. In previous work, the male
      beetles, but not females, were shown to produce (R)-3-hydroxy-2-hexanone, and
      female beetles were attracted to this compound in a laboratory bioassay. In this
      study, release rates of 3-hydroxy-2-hexanone from different dispensers were
      measured in the laboratory, and the attractiveness of these to X. arvicola adults
      was determined in trapping tests in three traditional wine-growing regions in
      Spain. RESULTS: As a result of laboratory experiments, for field experiments 3
      hydroxy-2-hexanone was formulated as 100 MUL in a polyethylene sachet (50 mm * 50
      mm * 250 um), and ethanol was formulated as 1 mL in a polyethylene press-seal bag
      (76 mm * 57 mm *50 um). Field catches were similar at all three study sites.
      Catches in traps baited with 3-hydroxy-2-hexanone alone were not significantly
      different from those in unbaited control traps, but catches in traps baited with
      3-hydroxy-2-hexanone and ethanol in separate sachets, with 3-hydroxy-2-hexanone
      and ethanol in the same sachet or with ethanol alone were significantly greater
      than those in control traps. These results confirm that the beetles are attracted
      to ethanol, and the addition of 3-hydroxy-2-hexanone does not seem to make any
      difference. CONCLUSIONS: Attraction of females for the male-produced compound (R)
      3-hydroxy-2-hexanone has been observed in laboratory but not in field
      experiments. Traps baited with ethanol are highly attractive to both sexes of
      adults of X. arvicola, and these can be used for improved monitoring of the adult
      emergence and for population control by mass trapping. (c) 2016 Society of
      Chemical Industry.

PMID- 27885783
TI  - Protective effects of a novel nutritional and phytonutrient blend on ultraviolet
      radiation-induced skin damage and inflammatory response through aging defense
      mechanisms.
AB  - BACKGROUND: The human body relies on several aging defense mechanisms (ADMs) to
      limit damage induced from pro-aging stressors (aging aggressors). However, such
      protective mechanisms can be compromised, leading to accelerated aging. The skin
      provides a model to probe the effects of an oral nutritional intervention on ADMs
      in response to ultraviolet radiation (UVR)-induced damage. OBJECTIVE: To
      determine whether supplementation with a novel nutritional and phytonutrient
      blend could protect against UVR-induced skin damage and positively influence
      facial skin attributes and characteristics by bolstering ADMs. METHODS: Thirty
      six healthy, nonsmoking women (40-75 years) with Fitzpatrick skin types I and II
      were recruited. UVR-induced erythema and the number of apoptotic cells were
      determined before (pre-) and after 8-week (post-) supplementation. Other clinical
      variables included skin carotenoid concentrations, facial skin attributes and
      characteristics. RESULTS: Eight-week supplementation led to protection against
      UVR-induced skin damage as evidenced by reductions in erythema at all three
      minimal erythema doses (MEDs) (9.1 to 7.4 [P = 0.10]; 15.8 to 13.6 [P = 0.02];
      and 19.6 to 17.3 [P = 0.01] for one, two, and three MEDs and a reduction in the
      average number of apoptotic cells [11.3 to 5.3, P < 0.0001] pre- and post
      supplementation, respectively). Skin carotenoid concentrations increased from 28
      111 Raman intensity units to 38 472 (P < 0.0001) along with noticeable
      improvements in facial skin attributes and characteristics: elasticity,
      transepidermal water loss, radiance, texture, and overall appearance (all P <
      0.05) following supplementation. CONCLUSION: Eight weeks of oral supplementation
      positively impacted ADMs resulting in protection against UVR-induced skin damage
      and improvements in facial skin attributes and characteristics.

PMID- 27885784
TI  - MicroRNA and dsRNA targeting chitin synthase A reveal a great potential for pest
      management of the hemipteran insect Nilaparvata lugens.
AB  - BACKGROUND: Two RNA silencing pathways in insects are known to exist that are
      mediated by short interfering RNAs (siRNAs) and microRNAs (miRNAs), which have
      been hypothesised to be promising methods for insect pest control. However, a
      comparison between miRNA and siRNA in pest control is still unavailable,
      particularly in targeting chitin synthase gene A (CHSA). RESULTS: The dsRNA for
      Nilaparvata lugens CHSA (dsNlCHSA) and the microR-2703 (miR-2703) mimic targeting
      NlCHSA delivered via feeding affected the development of nymphs, reduced their
      chitin content and led to lethal phenotypes. The protein level of NlCHSA was
      downregulated after female adults were injected with dsNlCHSA or the miR-2703
      mimic, but there were no significant differences in vitellogenin (NlVg)
      expression or in total oviposition relative to the control group. However, 90.68
      and 46.13% of the eggs laid by the females injected with dsNlCHSA and miR-2703
      mimic were unable to hatch, respectively. In addition, a second-generation miRNA
      and RNAi effect on N. lugens was observed. CONCLUSION: Ingested miR-2703 seems to
      be a good option for killing N. lugens nymphs, while NlCHSA may be a promising
      target for RNAi-based pest management. These findings provide important evidence
      for applications of small non-coding RNAs (snRNAs) in insect pest management. (c)
      2016 Society of Chemical Industry.

PMID- 27885785
TI  - Osteogenic activity and antibacterial effect of porous titanium modified with
      metal-organic framework films.
AB  - As a new class of crystalline nanoporous materials, metal-organic frameworks
      (MOFs) have recently been used for biomedical applications due to their large
      surface area, high porosity, and theoretically infinite structures. To improve
      the biological performance of titanium, MOF films were applied to surface
      modification of titanium. Zn-based MOF films composed of zeolitic imidazolate
      framework-8 (ZIF-8) crystals with nanoscale and microscale sizes (nanoZIF-8 and
      microZIF-8) were prepared on porous titanium surfaces by hydrothermal and
      solvothermal methods, respectively. The ZIF-8 films were characterized by powder
      X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and
      scanning electron microscopy (SEM). The nanoZIF-8 film exhibited good
      biocompatibility, whereas the microZIF-8 film showed obvious cytotoxicity to MG63
      cells. Compared to pure titanium and alkali- and heat-treated porous titanium,
      the nanoZIF-8 film not only enhanced alkaline phosphatase (ALP) activity,
      extracellular matrix mineralization, and expression of osteogenic genes (ALP,
      Runx2) in MG63 cells but also inhibited the growth of Streptococcus mutans. These
      results indicate that MOF films or coatings may be promising candidates for bone
      tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      105A: 834-846, 2017.

PMID- 27885786
TI  - Effects of flaxseed oil on blood hepcidin and hematologic factors in hemodialysis
      patients.
AB  - INTRODUCTION: In hemodialysis (HD) patients, one of the common complications is
      renal anemia. Therefore, the present study was designed to investigate the
      effects of flaxseed oil consumption on blood hepcidin and hematologic factors in
      HD patients. METHODS: In this randomized, double-blind, clinical trial, 38 HD
      patients were randomly assigned to either the flaxseed oil or the control group.
      The patients in the flaxseed oil group received 6 g/d flaxseed oil for 8 wk,
      whereas the control group received 6 g/d medium chain triglycerides (MCT) oil. At
      baseline and the end of week 8, serum hepcidin, and blood hemoglobin, hematocrit,
      red blood cells (RBCs), mean corpuscular volume (MCV), mean corpuscular
      hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were
      measured after a 12- to 14-h fast. FINDINGS: Flaxseed oil consumption
      significantly reduced serum hepcidin concentration up to 25% during 8 weeks, and
      the reduction was significant in comparison with the MCT oil group. In addition,
      the number of RBCs, blood hemoglobin, hematocrit, MCH and MCHC increased
      significantly in the flaxseed oil group up to 6%, 10%, 6%, 5%, and 2%,
      respectively, and these elevations were significant in comparison with the MCT
      oil group. There was no significant difference between the two groups in mean
      changes of MCV. DISCUSSION: This study indicates that daily consumption of 6 g
      flaxseed oil reduces serum hepcidin and improves hematologic factors in HD
      patients.

PMID- 27885787
TI  - Cyclic Amino(Ylide) Silylene: A Stable Heterocyclic Silylene with Strongly
      Electron-Donating Character.
AB  - An isolable heterocyclic silylene (4) with two different pi-donating
      substituents, namely a classical amino group and a more electropositive and
      stronger carbon-based pi-donating phosphonium ylide, was synthesized and fully
      characterized. The combination of these two different pi-donating substituents
      confers high thermal stability and an unusual nucleophilic character on silylene
      4. Therefore, silylene 4 behaves as a strong donor ligand toward transition
      metals with a donating character comparable to N-heterocyclic carbenes, in
      contrast to classical N-heterocyclic silylenes, which generally present a weak
      donating character.

PMID- 27885788
TI  - Barriers to live donor kidney transplants in the pediatric population: A single
      center experience.
AB  - A decrease in live donor pediatric kidney transplants has occurred in the United
      States. This study investigates barriers that may influence access to live donor
      kidney transplants in children. Retrospective chart review was conducted for 91
      children (69% male, mean age 11.9 years) who underwent pretransplant workup from
      2005 to 2015 at an urban pediatric hospital. Fifty-four percent were African
      American, 32% Caucasian, 8% Arabic, 3% Hispanic, and 3% Others. Government
      sponsored insurance (Medicaid/Medicare) was utilized by 73%, and 54% had dual
      caregivers. Only nine of 68 kidney transplants were live donor transplants. Live
      donor transplants (11%) were significantly (P=.008) lower than deceased donor
      transplants (59%) in African Americans. Private insurance was reported by 56% of
      live donor recipients and 25% of deceased donor recipients. Among live donor
      recipients, 78% were from dual caregiver families. Caregiver, health-related,
      financial, and religious/cultural barriers to live donor transplants were
      reported, several of which may be amenable to positive intervention.

PMID- 27885789
TI  - Zika virus associated microcephaly/micrencephaly-fetal brain imaging in
      comparison with neuropathology.

PMID- 27885790
TI  - Hardiness, avoidance coping, and alcohol consumption in war veterans: A moderated
      mediation study.
AB  - Military personnel often engage in excessive alcohol use after returning from
      deployments. Thus far, research has paid scant attention to personality factors
      that may increase or diminish the risk for increased alcohol consumption in this
      population. The present study explores how psychological hardiness, avoidance
      coping, and stress exposure may interact to influence alcohol consumption
      patterns in soldiers following deployment. U.S. Army National Guard soldiers (N =
      357) were surveyed shortly after returning from combat operations in Afghanistan.
      Conditional process analysis was used to test for mediation and moderation
      effects. Mediation effects were further tested in a replication sample of
      Norwegian Army soldiers (N = 230) deployed to Kosovo. Findings show that
      hardiness is a significant (negative) predictor of increased alcohol use and that
      this relation is mediated by avoidance coping. Further, this effect was moderated
      by combat stress exposure in the U.S. sample, such that the mediation is stronger
      for those with greater exposure (moderated-mediation). Avoidance coping also
      mediated the effects of hardiness on alcohol consumption in the Norwegian sample.
      These findings suggest that avoidance coping and hardiness may be fruitful areas
      for interventions aimed at reducing risky drinking in high-stress groups like the
      military.

PMID- 27885792
TI  - Editorial overview: Membrane traffic and cell polarity.

PMID- 27885791
TI  - Simple and fast analysis of tetrabromobisphenol A, hexabromocyclododecane
      isomers, and polybrominated diphenyl ethers in serum using solid-phase extraction
      or QuEChERS extraction followed by tandem mass spectrometry coupled to HPLC and
      GC.
AB  - Two simplified sample preparation procedures for simultaneous extraction and
      clean-up of tetrabromobisphenol A, alpha-, beta-, and gamma
      hexabromocyclododecane and polybrominated diphenyl ethers in human serum were
      developed and validated. The first procedure was based on solid-phase extraction.
      Sample extraction, purification, and lipid removal were carried out directly on
      an Oasis HLB cartridge. The second procedure was a quick, easy, cheap, effective,
      rugged, and safe-based approach using octadecyl-modified silica particles as a
      sorbent. After sample extraction and cleanup, tetrabromobisphenol
      A/hexabromocyclododecane was separated from polybrominated diphenyl ethers by
      using a Si-based cartridge. Tetrabromobisphenol A and hexabromocyclododecane were
      then detected by high-performance liquid chromatography coupled to tandem mass
      spectrometry, while polybrominated diphenyl ethers were detected by gas
      chromatography coupled to tandem mass spectrometry. The results of the spike
      recovery test using fetal bovine serum showed that the average recoveries of the
      analytes ranged from 87.3 to 115.3% with relative standard deviations equal to or
      lower than 13.4 %. Limits of detection of the analytes were in the range of 0.4
      19 pg/mL except for decabromodiphenyl ether. The developed method was
      successfully applied to routine analysis of human serum samples from occupational
      workers and the general population. Extremely high serum polybrominated diphenyl
      ethers levels up to 3.32 * 104 ng/g lipid weight were found in occupational
      workers.

PMID- 27885793
TI  - Lipopolysaccharide binding protein predicts decompensated cirrhosis mortality? It
      is too early.

PMID- 27885794
TI  - A beekeeper's perspective on the neonicotinoid ban.
AB  - Bees and agrochemicals have a long history. For example, the first volume of
      IBRA's journal Bee World in 1919 contains mention of poisoning of bees by
      spraying an orchard with lead arsenate. Bees being insects, it is self-evident
      that the use of insecticides to control crop pests poses a risk to them. Bee
      poisoning incidents became a very serious problem in the 1960s and 1970s with
      spraying of, in particular, oilseed rape with organophosphorus compounds. The
      introduction of carbamates and then especially synthetic pyrethroids reduced
      these problems. Data from the Wildlife Incident Investigation Scheme show that in
      recent years there have been very few poisoning incidents in the United Kingdom
      that can be attributed to agricultural insecticides. The introduction of
      neonicotinoid insecticides has, however, been very controversial. Almost as soon
      as they were introduced in the 1990s, French beekeepers blamed colony losses on
      imidacloprid used on sunflowers and maize, but restrictions on its use did not
      lead to a reduction in losses or to a reduction in beekeepers' concerns. Acute
      pesticide poisoning incidents by neonicotinoids in Germany and Italy in 2008
      further sealed their reputation. Despite laboratory evidence showing their harm,
      field experience remains equivocal, and many commercial beekeepers continue to
      move their colonies to oilseed rape crops for honey production. The neonicotinoid
      moratorium has undoubtedly led to the increased use of older insecticides, and
      the effect of this on bee populations is unknown and unquantified. Many
      beekeepers are currently confused by the conflicting evidence. (c) 2016 Society
      of Chemical Industry.

PMID- 27885795
TI  - A digital tool for incorporating right atrial pressure into fractional flow
      reserve determination.

PMID- 27885797
TI  - Postpartum haemorrhage: a single definition is no longer enough.

PMID- 27885796
TI  - Hepatocellular carcinomas with intracellular hyaline bodies have a poor
      prognosis.
AB  - BACKGROUND & AIMS: Mallory-Denk bodies (MDBs) and intracellular hyaline bodies
      (IHBs) are cytoplasmic inclusions found in a subset of hepatocellular carcinoma
      (HCC). MDBs are mainly composed of the intermediate filament proteins keratin (K)
      8 and K18, the cellular stress- and adapter-protein sequestosome 1/p62 (p62) and
      ubiquitin, whereas IHBs consist of p62 and/or ubiquitin. Of note, cytoplasmic
      inclusions containing p62 can serve as markers of suppressed autophagy, which in
      turn has been associated with poor prognosis. The aim of this study was to
      evaluate the prognostic significance of p62-containing MDB and IHB in patients
      with HCC. METHODS: Ninety resected HCCs were assessed by H&E histology for MDB or
      IHB, and their presence was confirmed by immunohistochemistry using K8/18, p62
      and ubiquitin antibodies. The prognostic impact of inclusions was assessed using
      Kaplan-Meier and multivariate Cox proportional model. RESULTS: Mallory-Denk
      bodies and/or IHB were found in about 50% of HCC. Both types of inclusions were
      seen in 21%, MDB only in 19% and IHB only in 10% of cases. The presence of MDB in
      tumours was associated with the steatohepatitic variant of HCC, which also showed
      fatty change, ballooning of tumour cells, MDBs, inflammation and pericellular
      fibrosis (P<.001). In contrast, IHBs were not associated with steatohepatitic
      morphology but were associated with significantly shorter overall survival
      (P=.006). Multivariate analysis revealed macroscopic vascular invasion (P=.045)
      and presence of IHB in HCC cells (P=.005) as independently associated with
      overall survival. CONCLUSIONS: Intracellular hyaline bodies and macroscopic
      vascular invasion identify a subset of HCC patients with poor prognosis.

PMID- 27885798
TI  - In their own words: A short report of patients' experiences of recovering from
      total knee replacement.

PMID- 27885800
TI  - Sacral neuromodulation for the treatment of faecal incontinence following
      proctectomy.
AB  - AIM: This study assessed the effectiveness of sacral neuromodulation (SNM) for
      faecal incontinence (FI) following proctectomy with colorectal or coloanal
      anastomosis. METHODS: An Institutional Review Board (IRB)-approved database
      identified patients treated for FI following proctectomy (SNM-P) for benign or
      malignant disease, who were matched 1:1 according to preoperative Cleveland
      Clinic Florida Faecal Incontinence Scores (CCF-FIS) with patients without
      proctectomy (SNM-NP). Primary outcome was change in CCF-FIS. RESULTS: Twelve
      patients (seven women) were in the SNM-P group and 12 (all women) were in the SNM
      NP group. In the SNM-P group, six patients underwent proctectomy for low rectal
      cancer and five received neoadjuvant chemoradiation. Five patients had handsewn
      anastomosis, and one had stapled coloanal anastomosis. One lead explantation
      occurred after a failed 2-week SNM percutaneous trial. Six patients underwent
      proctectomy for benign conditions. Within-group analyses revealed significant
      improvement in CCF-FIS in the SNM-P group (reduction from a score of 18 to a
      score of 14; P = 0.02), which was more profound for benign disease (reduction
      from 14.5 to 8.5) than for rectal cancer (reduction from 19.5 to 15). SNM was
      explanted in 66% and 33% of patients after proctectomy for malignant and benign
      conditions, respectively. In the SNM-NP group, 41% underwent overlapping
      sphincteroplasty. One patient received chemoradiation for anal cancer. Within
      group analysis for the SNM-NP group showed significant improvement in CCF-FIS (a
      reduction from 17.5 to 4.0; P = 0.003). There was significant improvement in CCF
      FIS in patients without previous proctectomy (mean delta CCF-FIS: 11.1 vs 4.7; P
      = 0.011). Analysis of covariance (ANCOVA) reaffirmed that controls outperformed
      proctectomy patients (P = 0.006). CONCLUSION: SNM for FI after proctectomy
      appears less effective than SNM in patients without proctectomy, with high device
      explantation rates, particularly after neoadjuvant chemoradiation and proctectomy
      for low rectal cancer.

PMID- 27885799
TI  - The C-terminal extension of Mycobacterium tuberculosis Hsp16.3 regulates its
      oligomerization, subunit exchange dynamics and chaperone function.
AB  - Mycobacterium tuberculosis is a human pathogen that secretes a major
      immunodominant antigen, namely Hsp16.3, throughout the course of infection.
      Hsp16.3 belongs to the small heat shock protein family and exhibits a molecular
      chaperone function that is important for the growth and survival of M.
      tuberculosis in host cell macrophages. The importance of the N-terminal region
      for the structure and chaperone function of Hsp16.3 is well understood. However,
      the effect of the C-terminal region on these properties is far from clear.
      Therefore, we cloned, over-expressed and purified wild-type and seven C-terminal
      truncated mutant proteins of Hsp16.3. Mutants with deletions of one and two C
      terminal extension (CTE) residues had a structure and chaperone function similar
      to wild-type protein. Intriguingly, deletion of three residues from the CTE
      triggered perturbation of the tertiary structure, dissociation of the oligomeric
      assembly (dodecamer to octamer and dimer), enhancement of subunit exchange
      dynamics and improvement in the chaperone function of Hsp16.3. Interestingly,
      these structural modulations (except oligomeric dissociation) as well as
      chaperoning strength reached their apex upon truncation of the entire CTE (141
      RSTN144 ). Further deletions from the C-terminal region beyond the CTE increased
      only the degree of oligomeric dissociation, and the complete removal of this
      region made the protein into a dimer. Overall, our study suggests a 'new
      structural element' in the C-terminal region, i.e. the C-terminal extension,
      which plays an important role in the oligomerization, subunit exchange dynamics
      and chaperone function of Hsp16.3.

PMID- 27885801
TI  - Fraction transfer process in on-line comprehensive two-dimensional liquid-phase
      separations.
AB  - Two-dimensional liquid-phase separations have gained increasing attention for
      their ability to separate complex sample mixtures. Among the experimental setups
      used, an on-line approach is preferred to reduce the probability of sample
      contamination, for easier automation and high-sample throughput. The interfacing
      of the separation techniques in the on-line mode brings additional demands on
      proper optimization of the two-dimensional system. In this review, the
      possibilities of the on-line coupling of liquid chromatography and liquid
      chromatography with capillary electrophoresis in two-dimensional systems are
      discussed. Special attention is paid to the fraction transfer process, which
      includes an overview of interfaces and experimental setups applied, the
      compatibility issues of separation systems, and instrumental parameters. The
      benefits and drawbacks of using electromigration separations in combination with
      liquid chromatography are presented as well.

PMID- 27885803
TI  - Rapid and sensitive determination of phytosterols in functional foods and
      medicinal herbs by using UHPLC-MS/MS with microwave-assisted derivatization
      combined with dual ultrasound-assisted dispersive liquid-liquid microextraction.
AB  - In this work, a hyphenated technique of dual ultrasound-assisted dispersive
      liquid-liquid microextraction combined with microwave-assisted derivatization
      followed by ultra high performance liquid chromatography tandem mass spectrometry
      has been developed for the determination of phytosterols in functional foods and
      medicinal herbs. Multiple reaction monitoring mode was used for the tandem mass
      spectrometry detection. A mass spectrometry sensitive reagent, 4'-carboxy
      substituted rosamine, has been used as the derivatization reagent for five
      phytosterols, and internal standard diosgenin was used for the first time.
      Parameters for the dual microextraction, microwave-assisted derivatization, and
      ultra high performance liquid chromatography tandem mass spectrometry were all
      optimized in detail. Satisfactory linearity, recovery, repeatability, accuracy
      and precision, absence of matrix effect, extremely low limits of detection (0.005
      0.015 ng/mL) and limits of quantification (0.030-0.10 ng/mL) were achieved. The
      proposed method was compared with previously reported methods. It showed better
      sensitivity, selectivity, and accuracy. The matrix effect was also significantly
      reduced. The proposed method was successfully applied to the determination of
      five phytosterols in vegetable oil (sunflower oil, olive oil, corn oil, peanut
      oil), milk and orange juice (soymilk, peanut milk, orange juice), and medicinal
      herbs (Ginseng, Ganoderma lucidum, Cordyceps, Polygonum multiflorum) for the
      quality control of functional foods and medicinal herbs.

PMID- 27885804
TI  - Financial strain, dyadic coping, relationship satisfaction, and psychological
      distress: A dyadic mediation study in Greek couples.
AB  - Financial strain typically has a severe impact on a couple's functioning and the
      well-being of its members. In this study, we examined the indirect relation of
      financial strain to partners' relationship satisfaction and psychological
      distress, using dyadic coping as a mediator, in a sample of Greek couples. One
      hundred and eighteen couples participated in a cross-sectional study. Perceived
      material loss in the past and perceived threat of loss in the future were used as
      financial strain indices. The actor-partner interdependence mediation model was
      employed to test for the mediation hypotheses. According to the results, the
      complete mediation (i.e., only indirect) effects models showed an unsatisfactory
      fit to the data and were rejected. The partial mediation actor-partner
      interdependence mediation model revealed several statistically significant direct
      and indirect (actor and partner) effects of the financial strain indices. The
      results provide more support to the hypothesized mediated impact of financial
      strain on partners' relationship satisfaction than on psychological distress. The
      findings underline the importance of dyadic coping for couple's adaptation to
      financial strain. They also point to the need to examine responses to stress at a
      dyadic level.

PMID- 27885802
TI  - A novel P53/POMC/Galphas/SASH1 autoregulatory feedback loop activates mutated
      SASH1 to cause pathologic hyperpigmentation.
AB  - p53-Transcriptional-regulated proteins interact with a large number of other
      signal transduction pathways in the cell, and a number of positive and negative
      autoregulatory feedback loops act upon the p53 response. P53 directly controls
      the POMC/alpha-MSH productions induced by ultraviolet (UV) and is associated with
      UV-independent pathological pigmentation. When identifying the causative gene of
      dyschromatosis universalis hereditaria (DUH), we found three mutations encoding
      amino acid substitutions in the gene SAM and SH3 domain containing 1 (SASH1), and
      SASH1 was associated with guanine nucleotide-binding protein subunit-alpha
      isoforms short (Galphas). However, the pathological gene and pathological
      mechanism of DUH remain unknown for about 90 years. We demonstrate that SASH1 is
      physiologically induced by p53 upon UV stimulation and SASH and p53 is
      reciprocally induced at physiological and pathophysiological conditions. SASH1 is
      regulated by a novel p53/POMC/alpha-MSH/Galphas/SASH1 cascade to mediate
      melanogenesis. A novel p53/POMC/Galphas/SASH1 autoregulatory positive feedback
      loop is regulated by SASH1 mutations to induce pathological hyperpigmentation
      phenotype. Our study demonstrates that a novel p53/POMC/Galphas/SASH1
      autoregulatory positive feedback loop is regulated by SASH1 mutations to induce
      pathological hyperpigmentation phenotype.

PMID- 27885805
TI  - School absenteeism among school-aged children with medically attended acute viral
      respiratory illness during three influenza seasons, 2012-2013 through 2014-2015.
AB  - BACKGROUND: Acute respiratory illnesses (ARIs) are common in school-aged
      children, but few studies have assessed school absenteeism due to specific
      respiratory viruses. OBJECTIVE: To evaluate school absenteeism among children
      with medically attended ARI due to common viruses. METHODS: We analyzed follow-up
      surveys from children seeking care for acute respiratory illness who were
      enrolled in the influenza vaccine effectiveness study at Marshfield Clinic during
      the 2012-2013 through 2014-2015 influenza seasons. Archived influenza-negative
      respiratory swabs were retested using multiplex RT-PCR to detect 16 respiratory
      virus targets. Negative binomial and logistic regression models were used to
      examine the association between school absence and type of respiratory viruses;
      endpoints included mean days absent from school and prolonged (>2 days) absence.
      We examined the association between influenza vaccination and school absence
      among children with RT-PCR-confirmed influenza. RESULTS: Among 1027 children,
      2295 days of school were missed due to medically attended ARIs; influenza
      accounted for 39% of illness episodes and 47% of days missed. Mean days absent
      were highest for influenza (0.96-1.19) and lowest for coronavirus (0.62).
      Children with B/Yamagata infection were more likely to report prolonged absence
      than children with A/H1N1 or A/H3N2 infection [OR (95% CI): 2.1 (1.0, 4.5) and
      1.7 (1.0, 2.9), respectively]. Among children with influenza, vaccination status
      was not associated with prolonged absence. CONCLUSIONS: School absenteeism due to
      medically attended ARIs varies by viral infection. Influenza B infections
      accounted for the greatest burden of absenteeism.

PMID- 27885807
TI  - Loading of BMP-2-related peptide onto three-dimensional nano-hydroxyapatite
      scaffolds accelerates mineralization in critical-sized cranial bone defects.
AB  - Extrusion free-forming, as a rapid prototyping technique, is extensively applied
      in fabricating ceramic material in bone tissue engineering. To improve the
      osteoinductivity of nano-hydroxyapatite (nHA) scaffold fabricated by extrusion
      free-forming, in this study, we incorporated a new peptide (P28) and optimized
      the superficial microstructure after shaping by controlling the sintering
      temperature. P28, a novel bone morphogenic protein 2 (BMP-2)-related peptide, was
      designed in this study. Analysis of the structure, physicochemical properties and
      release kinetics of P28 from nHA sintered at temperatures ranging from 1000 
      degrees C to 1400  degrees C revealed that nHA sintered at 1000  degrees C had
      higher porosity, preferable pore size and better capacity to control P28 release
      than that sintered at other temperatures. Moreover, the nHA scaffold sintered at
      1000  degrees C with P28 showed improved adhesion, proliferation and osteogenic
      differentiation of MC3T3-E1 cells compared with scaffolds lacking P28 or BMP-2.
      In vivo, nHA scaffolds sintered at 1000  degrees C with P28 or BMP-2 induced
      greater bone regeneration in critical-sized rat cranial defects at 6 and 12 weeks
      post-implantation compared with scaffolds lacking P28 or BMP-2. Thus, nHA
      scaffolds sintered at 1000  degrees C and loaded with P28 may be excellent
      biomaterials for bone tissue engineering. Copyright (c) 2016 John Wiley & Sons,
      Ltd.

PMID- 27885806
TI  - Mental health of women entering fertility treatment: What role do age and
      internal resources play?
AB  - Drawing on Lazarus and Folkman's (1984) model of stress and coping, the study
      aimed at (a) examining the associations between the mental health of women
      entering fertility treatment and their internal resources (hope and two aspects
      of self-consciousness: reflection and rumination); (b) indicating whether mental
      health is associated with age (above or below 35), and whether this association
      is mediated by the internal resources. The sample consisted of 137 women (76 aged
      20-34; 61 aged 35-44) at the start of fertility treatment who completed a series
      of self-report questionnaires. Results indicated that younger women reported
      higher distress and rumination than older women. Higher hope was associated with
      greater well-being, and higher rumination was associated with greater distress.
      Furthermore, hope and rumination were found to mediate the association between
      age and mental health. These findings highlight the importance of developing age
      based interventions for women entering fertility treatment, aimed at
      strengthening their resilience to effectively cope with the demanding process
      ahead.

PMID- 27885808
TI  - VP1, the major capsid protein of the mouse polyomavirus, binds microtubules,
      promotes their acetylation and blocks the host cell cycle.
AB  - VP1, the major structural protein of the mouse polyomavirus (MPyV), is the major
      architectural component of the viral capsid. Its pentamers are able to self
      assemble into capsid-like particles and to non-specifically bind DNA. Surface
      loops of the protein interact with sialic acid of ganglioside receptors. Although
      the replication cycle of the virus, including virion morphogenesis, proceeds in
      the cell nucleus, a substantial fraction of the protein is detected in the
      cytoplasm of late-phase MPyV-infected cells. In this work, we detected VP1 mainly
      in the cytoplasm of mammalian cells transfected with plasmid expressing VP1. In
      the cytoplasm, VP1-bound microtubules, including the mitotic spindle, and the
      interaction of VP1 with microtubules resulted in cell cycle block at the G2/M
      phase. Furthermore, in the late phase of MPyV infection and in cells expressing
      VP1, microtubules were found to be hyperacetylated. We then sought to understand
      how VP1 interacts with microtubules. Dynein is not responsible for the VP1
      microtubule association, as neither overexpression of p53/dynamitin nor treatment
      with ciliobrevin-D (an inhibitor of dynein activity) prevented binding of VP1 to
      microtubules. A pull-down assay for VP1-interacting proteins identified the heat
      shock protein 90 (Hsp90) chaperone, and Hsp90 was also detected in the VP1
      microtubule complexes. Although Hsp90 is known to be associated with acetylated
      microtubules, it does not mediate the interaction between VP1 and microtubules.
      Our study provides insight into the role of the major structural protein in MPyV
      replication, indicating that VP1 is a multifunctional protein that participates
      in the regulation of cell cycle progression in MPyV-infected cells.

PMID- 27885809
TI  - Selective Production of Toluene from Biomass-Derived Isoprene and Acrolein.
AB  - Toluene is a basic chemical that is currently produced from petroleum resources.
      In this paper, we report a new route for the effective synthesis of toluene from
      isoprene and acrolein, two reactants readily available from biomass, through a
      simple two-step reaction. The process includes Diels-Alder cycloaddition of
      isoprene and acrolein in a Zn-containing ionic liquid at room temperature to
      produce methylcyclohex-3-enecarbaldehydes (MCHCAs) as intermediates, followed by
      M (M=Pt, Pd, Rh)/Al2 O3 -catalyzed consecutive dehydrogenation-decarbonylation of
      the MCHCAs at 573 K to generate toluene with an overall yield up to 90.7 %. Model
      reactions indicated that a synergistic inductive effect of the C=C double bond
      and the aldehyde group in MCHCA plays a key role in initiating the consecutive
      dehydrogenation-decarbonylation, and that methyl benzaldehydes are the key
      intermediates in the gas-phase transformation of MCHCAs. Microcalorimetric
      adsorption of CO on different catalysts showed that decarbonylation of the
      substrate occurs more likely on the strong adsorption sites. To the best of our
      knowledge, it is the first report of Pt/Al2 O3 -catalyzed consecutive
      dehydrogenation-decarbonylation of a given compound in one reactor. This work
      provides a highly efficient and environmental friendly route to toluene by
      utilizing two compounds that can be prepared from biomass.

PMID- 27885810
TI  - Value of 18 F-FDG PET/MRI for the outcome of CT-guided facet block therapy in
      cervical facet syndrome: initial results.
AB  - INTRODUCTION: The aim of this study was to evaluate the ability of 18 F
      fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18 F
      FDG PET/MRI) to detect PET-positive cervical facet arthropathy and identify
      patients who benefit from facet block therapy. METHODS: Ten patients with
      cervical facet syndrome (mean age: 65 +/- 12 years) underwent 18 F-FDG PET/MRI of
      the neck. Focal 18 F-FDG uptake in PET-positive facet joints served as target for
      computed tomography (CT)-guided facet blocks. In PET-negative patients, the
      target joint for facet block therapy was selected by current clinical standards
      considering the level of maximum facet arthrosis and pain. Neck pain was measured
      on visual analogue scale (VAS) before and after therapy. Bone marrow signal
      intensity (SI) ratio on turbo inversion recovery magnitude (TIRM) images and
      maximum standard uptake values (SUVmax) was calculated for each facet joint.
      Pearson's correlation coefficient (r) was calculated between bone marrow SI
      ratios on TIRM and SUVmax. RESULTS: 18 F-FDG PET/MRI detected PET-positive facet
      arthropathy in six patients. Patients with PET-positive facet arthropathy had
      significantly less pain compared with the pretreatment pain 3 h (P = 0.002), 4
      weeks (P = 0.002) and 3 months (P = 0.026) after facet block therapy. Pain did
      not change significantly in patients with PET-negative facet arthropathy. TIRM SI
      ratio was higher in PET-positive facet arthropathy than in PET-negative facet
      arthropathy (P < 0.001). Correlation was strong between bone marrow SI ratio on
      TIRM images and SUVmax (r = 0.7; P < 0.001). CONCLUSIONS: 18 F-FDG PET/MRI can
      detect PET-positive cervical facet arthropathy and help to identify patients
      benefitting from facet block therapy. Bone marrow TIRM SI ratio might be a
      surrogate for PET-positive facet arthropathy.

PMID- 27885811
TI  - 17,beta-estradiol inhibits hepatitis C virus mainly by interference with the
      release phase of its life cycle.
AB  - BACKGROUND & AIMS: Oestrogen and oestrogen-mediated signalling protect from
      hepatitis C virus through incompletely understood mechanisms. We aimed to
      ascertain which phase(s) of hepatitis C virus life cycle is/are affected by
      oestrogens. METHODS: Huh7 cells infected with the JFH1 virus (genotype 2a) were
      exposed to dehydroepiandrosterone, testosterone, progesterone and 17beta
      estradiol (tested with/without its receptor antagonist fulvestrant). Dose
      response curves were established to calculate half maximal inhibitory
      concentration values. To dissect how 17beta-estradiol interferes with phases of
      hepatitis C virus life cycle, its effects were measured on the hepatitis C virus
      pseudo-particle system (viral entry), the subgenomic replicon N17/JFH1 and the
      replicon cell line Huh7-J17 (viral replication). Finally, in a dual-step
      infection model, infectious supernatants, collected from infected cells exposed
      to hormones, were used to infect naive cells. RESULTS: Progesterone and
      testosterone showed no inhibitory effect on hepatitis C virus;
      dehydroepiandrosterone was only mildly inhibitory. In contrast, 17beta-estradiol
      inhibited infection by 64%-67% (IC50 values 140-160 nmol/L). Fulvestrant reverted
      the inhibition by 17beta-estradiol in a dose-dependent manner. 17beta-estradiol
      exerted only a slight inhibition (<20%) on hepatitis C virus pseudo-particles,
      and had no effect on cells either transiently or stably (Huh7-J17 cells)
      expressing the N17/JFH1 replicon. In the dual-step infection model, a significant
      half maximal inhibitory concentration decline occurred between primary (134
      nmol/L) and secondary (100 nmol/L) infections (P=.02), with extracellular
      hepatitis C virus RNA and infectivity being reduced to a higher degree in
      comparison to its intracellular counterpart. CONCLUSIONS: 17beta-estradiol
      inhibits hepatitis C virus acting through its intracellular receptors, mainly
      interfering with late phases (assembly/release) of the hepatitis C virus life
      cycle.

PMID- 27885813
TI  - A novel modelling approach to energy transport in a respiratory system.
AB  - In this paper, energy transport in a respiratory tract is modelled using the
      finite element method for the first time. The upper and lower respiratory tracts
      are approximated as a 1-dimensional domain with varying cross-sectional and
      surface areas, and the radial heat conduction in the tissue is approximated using
      the 1-dimensional cylindrical coordinate system. The governing equations are
      solved using 1-dimensional linear finite elements with convective and evaporative
      boundary conditions on the wall. The results obtained for the exhalation
      temperature of the respiratory system have been compared with the available
      animal experiments. The study of a full breathing cycle indicates that
      evaporation is the main mode of heat transfer, and convection plays almost
      negligible role in the energy transport. This is in-line with the results
      obtained from animal experiments.

PMID- 27885814
TI  - Trends, microbiology, and outcomes of infective endocarditis in children during
      2000-2010 in the United States.
AB  - BACKGROUND: We studied the incidence, trend, underlying conditions, microbiology,
      and outcomes of infective endocarditis (IE) in children during 11 years using
      Nationwide Inpatient Sample (NIS) database. This is the largest all-payer
      inpatient care database in the United States containing data for more than 8
      million hospital stays from over 1000 hospitals. METHODS: NIS data from 2000 to
      2010 of primary discharge diagnosis of IE in children aged <=19 years old were
      studied. Children with underlying congenital heart defects and acquired heart
      conditions were identified. Microbiological causative agents were recorded.
      Linear regression was used to assess trend of incidence over time. RESULTS: An
      estimated 3,840 (95% CI: 3,395-4,285) children had a discharge diagnosis of IE.
      The overall incidence was 0.43 per 100 000 children. The incidence was stable
      over the study period (P = .4 for trend). The majority of patients 56.2% were
      >=11 years old and 15.4% were <= 1 year. Underlying cardiac conditions were
      present in 53.5% of patients. Overall 30.2% of cases were culture-negative. Among
      those with identified pathogens, Staphylococcus species were most common (43.1%)
      followed by Streptococcus species (39.5%). Viridans Streptococcus group was most
      common in those with underlying heart disease (32.7%) and S. aureus was most
      common in those without heart disease (46.9%). Among culture-positive patients,
      there was a decline in proportion of Staphylococcal IE (P = .03) and an increase
      in proportion of Streptococcal IE (P = .04). Overall mortality was 2.8%. Patients
      with Staphylococcal IE had longer median length of stay (12 vs. 9 days; P < .01)
      and the highest mortality (4.7%). CONCLUSION: The incidence of IE in children has
      remained unchanged in the United States during the 11-year study period. Among
      culture-positive patients there was a significant decrease in Staphylococcal IE
      and a significant increase of Streptococcal IE. Staphylococcal IE was associated
      with increased LOS and highest mortality.

PMID- 27885816
TI  - Recent advances in pediatric rheumatology: July-September 2016.

PMID- 27885812
TI  - A whole animal chemical screen approach to identify modifiers of intestinal
      neutrophilic inflammation.
AB  - By performing two high-content small molecule screens on dextran sodium sulfate-
      and trinitrobenzene sulfonic acid-induced zebrafish enterocolitis models of
      inflammatory bowel disease, we have identified novel anti-inflammatory drugs from
      the John Hopkins Clinical Compound Library that suppress neutrophilic
      inflammation. Live imaging of neutrophil distribution was used to assess the
      level of acute inflammation and concurrently screen for off-target drug effects.
      Supporting the validity of our screening strategy, most of the anti-inflammatory
      drug hits were known antibiotics or anti-inflammatory agents. Novel hits included
      cholecystokinin (CCK) and dopamine receptor agonists. Using a pharmacological
      approach, we show that while CCK and dopamine receptor agonists alleviate
      enterocolitis-associated inflammation, receptor antagonists exacerbate
      inflammation in zebrafish. This work highlights the utility of small molecule
      screening in zebrafish enterocolitis models as a tool to identify novel bioactive
      molecules capable of modulating acute inflammation.

PMID- 27885817
TI  - Serum ferritin level is a prognostic marker in patients with peripheral T-cell
      lymphoma.
AB  - INTRODUCTION: The prognostic value of serum ferritin level in patients with
      peripheral T-cell lymphoma (PTCL) remains unknown. METHODS: We retrospectively
      analyzed clinical data from 78 consecutive patients with newly diagnosed PTCL
      that were treated with anthracycline-containing regimens between 1998 and 2011.
      RESULTS: The patients consisted of 50 males and 28 females with a median age of
      64 years (range, 16-83 years). The subtypes of PTCL were 39 PTCL, not otherwise
      specified and 39 angioimmunoblastic T-cell lymphoma (AITL). The median
      observation period for the surviving patients was 50 months. The overall survival
      (OS) was poorer in patients with serum ferritin level above the upper normal
      limit (n = 28), compared with patients with serum ferritin level within normal
      range (n = 50; 4-year OS: 23% vs. 72%; P < 0.001). In the multivariate analysis,
      poor performance status (P = 0.006) and elevated serum ferritin level (P = 0.018)
      were independent risk factors for poor OS. CONCLUSION: Serum ferritin level is a
      useful prognostic marker for PTCL.

PMID- 27885815
TI  - Changes in urine volume and serum albumin in incident hemodialysis patients.
AB  - INTRODUCTION: Hypoalbuminemia is a predictor of poor outcomes in dialysis
      patients. Among hemodialysis patients, there has not been prior study of whether
      residual kidney function or decline over time impacts serum albumin levels. We
      hypothesized that a decline in residual kidney function is associated with an
      increase in serum albumin levels among incident hemodialysis patients. METHODS:
      In a large national cohort of 38,504 patients who initiated hemodialysis during
      1/2007-12/2011, we examined the association of residual kidney function,
      ascertained by urine volume and renal urea clearance, with changes in serum
      albumin over five years across strata of baseline residual kidney function, race,
      and diabetes using case-mix adjusted linear mixed effects models. FINDINGS: Serum
      albumin levels increased over time. At baseline, patients with greater urine
      volume had higher serum albumin levels: 3.44 +/- 0.48, 3.50 +/- 0.46, 3.57 +/-
      0.44, 3.59 +/- 0.45, and 3.65 +/- 0.46 g/dL for urine volume groups of <300, 300
      <600, 600-<900, 900-<1,200, and >=1,200 mL/day, respectively (Ptrend  < 0.001).
      Over time, urine volume and renal urea clearance declined and serum albumin
      levels rose, while the baseline differences in serum albumin persisted across
      groups of urinary volume. In addition, the rate of decline in residual kidney
      function was not associated with the rate of change in albumin. DISCUSSION:
      Hypoalbuminemia in hemodialysis patients is associated with lower residual kidney
      function. Among incident hemodialysis patients, there is a gradual rise in serum
      albumin that is independent of the rate of decline in residual kidney function,
      suggesting that preservation of residual kidney function does not have a
      deleterious impact on serum albumin levels.

PMID- 27885818
TI  - The impact of bevacizumab in metastatic colorectal cancer with an intact primary
      tumor: Results from a large prospective cohort study.
AB  - BACKGROUND: Debate continues regarding the benefits versus risks of initial
      resection of the primary tumor in metastatic colorectal cancer (mCRC) patients
      with an asymptomatic primary tumor. Although the benefit of the anti-vascular
      endothelial growth factor agent bevacizumab alongside first-line chemotherapy in
      mCRC is established, the impact of bevacizumab on the intact primary tumor (IPT)
      is less well understood. METHODS: Data from an Australian mCRC registry were used
      to assess the impact of bevacizumab-based regimens in the presence of an IPT, to
      see if this differs from effects in resected primary tumor (RPT) patients and to
      understand the safety profile of bevacizumab in patients with IPT. Progression
      free survival (PFS), overall survival (OS) and safety endpoints were analyzed.
      RESULTS: Of 1204 mCRC patients, 826 (69%) were eligible for inclusion.
      Bevacizumab use was similar in both arms (IPT (64%) versus RPT (70%)); compared
      with chemotherapy alone, bevacizumab use was associated with significantly longer
      PFS (IPT: 8.5 months vs 4.7 months, P = 0.017; RPT: 10.8 months vs 5.8 months, P
      < 0.001) and OS (IPT: 20 months vs 14.8 months, P = 0.005; RPT: 24.4 months vs
      17.3 months, P = 0.004)).1 Bevacizumab use in an IPT was associated with more GI
      perforations (4.5% vs 1.8%, P = 0.210) but less frequent bleeding (1.5% vs 5.3%,
      P = 0.050) and thrombosis (1.5% vs 2.7%, P = 0.470), versus chemotherapy alone.
      Median survival was equivalent between patients that did or did not experience
      bevacizumab-related adverse events - 20.0 months versus 19.9 months, hazard ratio
      = 0.98, P = 0.623.1 CONCLUSIONS: The addition of bevacizumab significantly
      improved survival outcomes in mCRC with an IPT. The occurrence of bevacizumab
      related adverse events did not significantly impact survival outcomes.

PMID- 27885819
TI  - Annual banned-substance review: analytical approaches in human sports drug
      testing.
AB  - There has been an immense amount of visibility of doping issues on the
      international stage over the past 12 months with the complexity of doping
      controls reiterated on various occasions. Hence, analytical test methods
      continuously being updated, expanded, and improved to provide specific,
      sensitive, and comprehensive test results in line with the World Anti-Doping
      Agency's (WADA) 2016 Prohibited List represent one of several critical
      cornerstones of doping controls. This enterprise necessitates expediting the
      (combined) exploitation of newly generated information on novel and/or superior
      target analytes for sports drug testing assays, drug elimination profiles,
      alternative test matrices, and recent advances in instrumental developments. This
      paper is a continuation of the series of annual banned-substance reviews
      appraising the literature published between October 2015 and September 2016
      concerning human sports drug testing in the context of WADA's 2016 Prohibited
      List. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27885820
TI  - Coupling of homogeneous liquid-liquid extraction and dispersive liquid-liquid
      microextraction for the extraction and preconcentration of polycyclic aromatic
      hydrocarbons from aqueous samples followed by GC with flame ionization detection.
AB  - In the present study, a simple and rapid method for the extraction and
      preconcentration of some polycyclic aromatic hydrocarbons in water samples has
      been developed. In this method, two sample preparation methods were combined to
      obtain high extraction recoveries and enrichment factors for sensitive analysis
      of the selected analytes. In the first stage of the method, a homogeneous
      solution containing an aqueous solution and cyclohexyl amine is broken by the
      addition of a salt. After centrifugation, the upper collected phase containing
      the extracted analytes is subjected to the following dispersive liquid-liquid
      microextraction method. Rapid injection of the mixture of cyclohexyl amine
      resulted from the first stage and 1,1,2-trichloroethane (as an extraction
      solvent) into an acetic acid solution is led to form a cloudy solution. After
      centrifuging, the fine droplets of the extraction solvent are settled down in the
      bottom of the test tube, and an aliquot of it is analyzed by gas chromatography.
      Under the optimum extraction conditions, enrichment factors and limits of
      detection for the studied analytes were obtained in the ranges of 616-752 and
      0.08-0.20 MUg/L, respectively. The simplicity, high extraction efficiency, short
      sample preparation time, low cost, and safety demonstrated the efficiency of this
      method relative to other approaches.

PMID- 27885821
TI  - Exploring simulation in the internal medicine clerkship.
AB  - BACKGROUND: Simulation-based medical education has been shown to produce
      substantial educational benefits; however, the integration and effectiveness of
      high-fidelity simulation within the internal medicine (IM) clerkship remains
      largely unexplored. Investigators sought to determine the effectiveness of
      simulation in improving student confidence in acute coronary syndrome (ACS) and
      the Advanced Cardiac Life Support (ACLS) curriculum. Secondary goals included
      examining student perceptions of the role of simulation in medical education.
      METHODS: Investigators implemented a formative high-fidelity simulation
      curriculum in the IM clerkship at a large teaching institution. Third-year
      medical students enrolled in the IM clerkship between January and June 2014
      attended a simulation course during their ambulatory block. Following a 2-hour
      session, participants completed a 17-item questionnaire. Descriptive statistical
      analyses and a thematic qualitative analysis were performed. Integration of high
      fidelity simulation within the internal medicine clerkship remains largely
      unexplored RESULTS: The response rate was 100 per cent (n = 43). Students
      reported improvements in their ability to identify and manage ACS and ACLS before
      and after the simulation course: 93 per cent felt that simulation boosted their
      self-confidence in performing these tasks on a real patient; 86 per cent reported
      receiving useful feedback during the training sessions; 98 per cent agreed that
      their experience was enjoyable; and 95 per cent would recommend this course to
      other students. CONCLUSIONS: Internal medicine (IM) clerkship students
      participating in our pilot course demonstrated increased confidence in
      identifying and managing pathologies associated with ACS and arrhythmias.
      Students viewed simulation as an engaging and useful activity, desiring
      additional training sessions.

PMID- 27885822
TI  - From Type I to Type II: Design, Synthesis, and Characterization of Potent Pyrazin
      2-ones as DFG-Out Inhibitors of PDGFRbeta.
AB  - Reversible protein kinase inhibitors that bind in the ATP cleft can be classified
      as type I or type II binders. Of these, type I inhibitors address the active
      form, whereas type II inhibitors typically lock the kinase in an inactive form.
      At the molecular level, the conformation of the flexible activation loop holding
      the key DFG motif controls access to the ATP site, thereby determining an active
      or inactive kinase state. Accordingly, type I and type II kinase inhibitors bind
      to so-called DFG-in or DFG-out conformations, respectively. Based on our former
      study on highly selective platelet-derived growth factor receptor beta
      (PDGFRbeta) pyrazin-2-one type I inhibitors, we expanded this scaffold toward the
      deep pocket, yielding the highly potent and effective type II inhibitor 5 (4-[(4
      methylpiperazin-1-yl)methyl]-N-[3-[[6-oxo-5-(3,4,5-trimethoxyphenyl)-1H-pyrazin-3
      yl]methyl]phenyl]benzamide). In vitro characterization, including selectivity
      panel data from activity-based assays (300 kinases) and affinity-based assays (97
      kinases) of these PDGFRbeta type I (1; 5-(4-hydroxy-3-methoxy-phenyl)-3-(3,4,5
      trimethoxyphenyl)-1H-pyrazin-2-one) and II (5) inhibitors showing the same
      pyrazin-2-one chemotype are compared. Implications are discussed regarding the
      data for selectivity and efficacy of type I and type II ligands.

PMID- 27885823
TI  - Novel functionalization strategies of polymeric nanoparticles as carriers for
      brain medications.
AB  - For targeted brain delivery, nanoparticles (NPs) should bypass the blood-brain
      barrier (BBB). Novel functionalization strategies, based on low-density
      lipoprotein receptor (LDLR) binding domain, have been here tested to increase the
      brain targeting efficacy of poly d,l-lactic-co-glycolic acid (PLGA) NPs,
      biodegradable and suited for biomedical applications. Custom-made PLGA NPs were
      functionalized with an apolipoprotein E modified peptide (pep-apoE) responsible
      for LDLR binding, or with lipocalin-type prostaglandin-d-synthase (L-PGDS),
      highly expressed in the brain. At the comparison of pep-apoE and L-PGDS
      sequences, a highly homologs region was here identified, indicating that also L
      PGDS could bind LDLR. Non-functionalized and functionalized NPs did not affect
      the viability of cultured human dendritic cells, protagonists of the immune
      response, and did not activate them to a proinflammatory profile. At 2 h after
      intravenous injection in mice, functionalized, but not the non-functionalized
      ones, fluorescent-tagged NPs were observed in the cerebral cortex parenchyma. The
      NPs were mostly internalized by neurons and microglia; glial cells showed a weak
      activation. The findings indicate that the tested functionalization strategies do
      not elicit adverse immune responses and that the peptidic moieties enable BBB
      traversal of the NPs, thus providing potential brain drug carriers. These could
      be especially effective for brain diseases in which LDLR is involved. (c) 2016
      Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 847-858, 2017.

PMID- 27885824
TI  - The Quest for Value-Added Products from Carbon Dioxide and Water in a Dielectric
      Barrier Discharge: A Chemical Kinetics Study.
AB  - Recycling of carbon dioxide by its conversion into value-added products has
      gained significant interest owing to the role it can play for use in an
      anthropogenic carbon cycle. The combined conversion with H2 O could even mimic
      the natural photosynthesis process. An interesting gas conversion technique
      currently being considered in the field of CO2 conversion is plasma technology.
      To investigate whether it is also promising for this combined conversion, we
      performed a series of experiments and developed a chemical kinetics plasma
      chemistry model for a deeper understanding of the process. The main products
      formed were the syngas components CO and H2 , as well as O2 and H2 O2 , whereas
      methanol formation was only observed in the parts-per-billion to parts-per
      million range. The syngas ratio, on the other hand, could easily be controlled by
      varying both the water content and/or energy input. On the basis of the model,
      which was validated with experimental results, a chemical kinetics analysis was
      performed, which allowed the construction and investigation of the different
      pathways leading to the observed experimental results and which helped to clarify
      these results. This approach allowed us to evaluate this technology on the basis
      of its underlying chemistry and to propose solutions on how to further improve
      the formation of value-added products by using plasma technology.

PMID- 27885825
TI  - Multiphase fluid-solid coupled analysis of shock-bubble-stone interaction in
      shockwave lithotripsy.
AB  - A novel multiphase fluid-solid-coupled computational framework is applied to
      investigate the interaction of a kidney stone immersed in liquid with a
      lithotripsy shock wave (LSW) and a gas bubble near the stone. The main objective
      is to elucidate the effects of a bubble in the shock path to the elastic and
      fracture behaviors of the stone. The computational framework couples a finite
      volume 2-phase computational fluid dynamics solver with a finite element
      computational solid dynamics solver. The surface of the stone is represented as a
      dynamic embedded boundary in the computational fluid dynamics solver. The
      evolution of the bubble surface is captured by solving the level set equation.
      The interface conditions at the surfaces of the stone and the bubble are enforced
      through the construction and solution of local fluid-solid and 2-fluid Riemann
      problems. This computational framework is first verified for 3 example problems
      including a 1D multimaterial Riemann problem, a 3D shock-stone interaction
      problem, and a 3D shock-bubble interaction problem. Next, a series of shock
      bubble-stone-coupled simulations are presented. This study suggests that the
      dynamic response of a bubble to LSW varies dramatically depending on its initial
      size. Bubbles with an initial radius smaller than a threshold collapse within 1
      MUs after the passage of LSW, whereas larger bubbles do not. For a typical LSW
      generated by an electrohydraulic lithotripter (pmax  = 35.0MPa, pmin  =-
      10.1MPa), this threshold is approximately 0.12mm. Moreover, this study suggests
      that a noncollapsing bubble imposes a negative effect on stone fracture as it
      shields part of the LSW from the stone. On the other hand, a collapsing bubble
      may promote fracture on the proximal surface of the stone, yet hinder fracture
      from stone interior.

PMID- 27885826
TI  - Posterior reversible encephalopathy syndrome due to combination of vemurafenib
      and cobimetinib for metastatic melanoma.

PMID- 27885828
TI  - Superionic Conductivity in Hybrid of 3-Hydroxypropanesulfonic Acid and Graphene
      Oxide.
AB  - Insertion of 3-hydroxypropanesulfonicacid (HPS) in the graphene oxide (GO)
      interlayer results in high proton conductivity (10-2 -10-1  S cm-1 ), owing to an
      improvement in oxygen content, interlayer distance and water absorbing capacity.
      This result indicates that hydroxyalkylsulfonicacids can be perfect guest
      molecules for improving the proton conductivity of carbon materials.

PMID- 27885827
TI  - A Mathematical Modeling Approach to Understanding the Effect of Anti-Interleukin
      Therapy on Eosinophils.
AB  - Emerging T-helper type 2 (Th2 ) cytokine-based asthma therapies, such as
      tralokinumab, lebrikizumab (anti-interleukin (IL)-13), and mepolizumab (anti-IL
      5), have shown differences in their blood eosinophil (EOS) response. To better
      understand these effects, we developed a mathematical model of EOS dynamics. For
      the anti-IL-13 therapies, lebrikizumab and tralokinumab, the model predicted an
      increase of 30% and 10% in total and activated EOS in the blood, respectively,
      and a decrease in the total and activated EOS in the airways. The model predicted
      a rapid decrease in total and activated EOS levels in blood and airways for the
      anti-IL-5 therapy mepolizumab. All model-based predictions were consistent with
      published clinical observations. The modeling approach provided insights into EOS
      response after treatment with Th2 -targeted therapies, and supports the
      hypothesis that an increase in blood EOS after anti-IL-13 therapy is part of the
      pharmacological action of these therapies.

PMID- 27885830
TI  - Extended dual antiplatelet therapy after acute coronary syndrome in Spain:
      Results from the EPICOR study.
AB  - INTRODUCTION: Real-world, country-specific studies of dual antiplatelet therapy
      (DAPT) duration among survivors of acute coronary syndrome (ACS) are important
      for improving long-term prognosis. AIMS: To investigate DAPT duration after
      hospital discharge for ACS in Spain. RESULTS: Data from patients enrolled in the
      Spanish cohort of the EPICOR (long-tErm follow-up of antithrombotic management
      Patterns In acute CORonary syndrome patients) study (NCT01171404) were analyzed
      for changes to antithrombotic medication up to 2 years postdischarge according to
      index event diagnosis and patient characteristics. Deaths, coronary events, and
      bleeding events were analyzed over the same period. Overall, a high proportion of
      patients remained on DAPT at 2 years (53.1%). Among patients who experienced any
      on-treatment bleeding event, almost two-thirds remained on DAPT at the end of
      follow-up. Patients >65 years, diabetic, or those that were medically managed
      were more likely to continue with DAPT until 2 years following discharge. At 2
      years, the incidence of bleeding events requiring hospitalization was low
      compared with the incidence of coronary events (1.4% vs 6.6%). There was a
      numerical reduction in coronary events, but no increase in bleeding events, with
      DAPT continuation compared with single antiplatelet therapy. CONCLUSIONS: More
      than half of patients in this unselected cohort study remained on DAPT at 2 years
      following discharge for ACS. Continuation with DAPT was greater among patients
      with additional cardiovascular risk factors, which suggests that treating
      physicians in Spain prioritizes ischemic risk reduction over bleeding risk in
      patients with ACS, according to patient's risk profile.

PMID- 27885829
TI  - Autoclave Sterilization of PEDOT:PSS Electrophysiology Devices.
AB  - Autoclaving, the most widely available sterilization method, is applied to
      poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS)
      electrophysiology devices. The process does not harm morphology or electrical
      properties, while it effectively kills E. coli intentionally cultured on the
      devices. This finding paves the way to widespread introduction of PEDOT:PSS
      electrophysiology devices to the clinic.

PMID- 27885832
TI  - Defining pediatric inpatient cardiology care delivery models: A survey of
      pediatric cardiology programs in the USA and Canada.
AB  - BACKGROUND: The treatment of children with cardiac disease is one of the most
      prevalent and costly pediatric inpatient conditions. The design of inpatient
      medical services for children admitted to and discharged from noncritical
      cardiology care units, however, is undefined. North American Pediatric Cardiology
      Programs were surveyed to define noncritical cardiac care unit models in current
      practice. METHOD: An online survey that explored institutional and functional
      domains for noncritical cardiac care unit was crafted. All questions were multi
      choice with comment boxes for further explanation. The survey was distributed by
      email four times over a 5-month period. RESULTS: Most programs (n = 45, 60%)
      exist in free-standing children's hospitals. Most programs cohort cardiac
      patients on noncritical cardiac care units that are restricted to cardiac
      patients in 39 (54%) programs or restricted to cardiac and other subspecialty
      patients in 23 (32%) programs. The most common frontline providers are
      categorical pediatric residents (n = 58, 81%) and nurse practitioners (n = 48,
      67%). However, nurse practitioners are autonomous providers in only 21 (29%)
      programs. Only 33% of programs use a postoperative fast-track protocol. When
      transitioning care to referring physicians, most programs (n = 53, 72%) use
      facsimile to deliver pertinent patient information. Twenty-two programs (31%) use
      email to transition care, and eighteen (25%) programs use verbal communication.
      CONCLUSION: Most programs exist in free-standing children's hospitals in which
      the noncritical cardiac care units are in some form restricted to cardiac
      patients. While nurse practitioners are used on most noncritical cardiac care
      units, they rarely function as autonomous providers. The majority of programs in
      this survey do not incorporate any postoperative fast-track protocols in their
      practice. Given the current era of focused handoffs within hospital systems,
      relatively few programs utilize verbal handoffs to the referring pediatric
      cardiologist/pediatrician.

PMID- 27885831
TI  - A Bioinspired Ultraporous Nanofiber-Hydrogel Mimic of the Cartilage Extracellular
      Matrix.
AB  - A true biomimetic of the cartilage extracellular matrix (ECM) could greatly
      contribute to our ability to regenerate this tissue in a mechanically demanding,
      often inflamed environment. Articular cartilage is a composite tissue made of
      cells and fibrillar proteins embedded in a hydrophilic polymeric meshwork. Here,
      a polyanionic functionalized alginate is used to mimic the glycosaminoglycan
      component of the native ECM. To create the fibrillar component,
      cryoelectrospinning of poly(epsilon-caprolactone) on a -78  degrees C mandrel,
      subsequently treated by O2 plasma, is used to create a stable, ultraporous and
      hydrophillic nanofiber network. In this study, cell-laden, fiber-reinforced
      composite scaffolds thicker than 1.5 mm can be created by infiltrating a
      chondrocyte/alginate solution into the fiber mesh, which is then physically cross
      linked. The fibrillar component significantly reinforces the chondroinductive,
      but mechanically weak sulfated alginate hydrogels. This allows the production of
      a glycosaminoglycan- and collagen type II-rich matrix by the chondrocytes as well
      as survival of the composite in vivo. To further enhance the system, the
      electrospun component is loaded with dexamethasone, which protected the cells
      from an IL-1beta-mediated inflammatory insult.

PMID- 27885833
TI  - Identification of the novel HLA-DRB1*08:69 allele by polymerase chain reaction
      sequence-based typing in a Chinese cord blood donor.
AB  - HLA-DRB1*08:69 has one nucleotide change from HLA-DRB1*08:03:02 at position 262
      G>A.

PMID- 27885834
TI  - Presence of an Immune System Increases Anti-Tumor Effect of Ag Nanoparticle
      Treated Mice.
AB  - To date, most nanomedical studies rely on the use of immune-deficient mice in
      which the contribution of the immune system on the applied therapy is ignored.
      Here, the degradation of silver nanoparticles (Ag NPs) is exploited as a means to
      treat subcutaneous tumor models in mice. To investigate the impact of the immune
      system, the same tumor cell type (KLN 205 murine squamous cell carcinoma) is used
      in a xenograft model in NOD SCIDgamma immune-deficient mice and as a syngeneic
      model in immune-competent DBA/2 mice. The Ag NPs are screened for their
      cytotoxicity on various cancer cell lines, indicating a concentration-dependent
      induction of oxidative stress, mitochondrial damage, and autophagy on all cell
      types tested. At subcytotoxic concentrations, prolonged cellular exposure to the
      Ag NPs results in toxicity due to NP degradation and the generation of toxic Ag+
      ions. At subcytotoxic conditions, the NPs are found to cause inflammation in
      vitro. Similar results are obtained in the immune-competent mouse model, where
      clear inflammation is observed after treatment of the implanted tumors with Ag
      NPs. This inflammation leads to an ongoing antitumoral effect, which results in a
      significantly reduced tumor growth compared to Ag NP-treated tumors in an immune
      deficient model.

PMID- 27885835
TI  - Sequential Enzymatic Conversion of alpha-Angelica Lactone to gamma-Valerolactone
      through Hydride-Independent C=C Bond Isomerization.
AB  - A case of hydride-independent reaction catalyzed by flavin-dependent ene
      reductases from the Old Yellow Enzyme (OYE) family was identified. alpha-Angelica
      lactone was isomerized to the conjugated beta-isomer in a nicotinamide-free and
      hydride-independent process. The catalytic cycle of C=C bond isomerization
      appears to be flavin-independent and to rely solely on a deprotonation
      reprotonation sequence through acid-base catalysis. Key residues in the enzyme
      active site were mutated and provided insight on important mechanistic features.
      The isomerization of alpha-angelica lactone by OYE2 in aqueous buffer furnished
      6.3 mm beta-isomer in 15 min at 30  degrees C. In presence of nicotinamide
      adenine dinucleotide (NADH), the latter could be further reduced to gamma
      valerolactone. This enzymatic tool was successfully applied on semi-preparative
      scale and constitutes a sustainable process for the valorization of platform
      chemicals from renewable resources.

PMID- 27885836
TI  - Texture analysis of medical images for radiotherapy applications.
AB  - The high-throughput extraction of quantitative information from medical images,
      known as radiomics, has grown in interest due to the current necessity to
      quantitatively characterize tumour heterogeneity. In this context, texture
      analysis, consisting of a variety of mathematical techniques that can describe
      the grey-level patterns of an image, plays an important role in assessing the
      spatial organization of different tissues and organs. For these reasons, the
      potentiality of texture analysis in the context of radiotherapy has been widely
      investigated in several studies, especially for the prediction of the treatment
      response of tumour and normal tissues. Nonetheless, many different factors can
      affect the robustness, reproducibility and reliability of textural features, thus
      limiting the impact of this technique. In this review, an overview of the most
      recent works that have applied texture analysis in the context of radiotherapy is
      presented, with particular focus on the assessment of tumour and tissue response
      to radiations. Preliminary, the main factors that have an influence on features
      estimation are discussed, highlighting the need of more standardized image
      acquisition and reconstruction protocols and more accurate methods for region of
      interest identification. Despite all these limitations, texture analysis is
      increasingly demonstrating its ability to improve the characterization of
      intratumour heterogeneity and the prediction of clinical outcome, although
      prospective studies and clinical trials are required to draw a more complete
      picture of the full potential of this technique.

PMID- 27885837
TI  - Imaging findings of flexion type of hangman's fracture; an attempt for a more
      objective evaluation with newly introduced scoring system.
AB  - OBJECTIVE: To identify the flexion type of hangman's fracture on imaging studies.
      METHODS: 38 cases of hangman's fracture were retrospectively studied and
      categorized into flexion and non-flexion groups. Plain radiograph, CT and MRI of
      these patients were evaluated; 13 radiological parameters that might define
      flexion injuries were measured. The data were statistically analyzed to identify
      good criteria and to rank them according to their importance in predicting
      flexion. RESULTS: Seven radiological criteria that have the highest correlation
      with flexion injury were identified. These are C2-3 lower end-plate angle, C2-3
      posterior body angle, interspinous angle, disc disruption (MRI), widening of
      interspinous distance, disruption of the posterior ligamentous complex (MRI) and
      angle at the fracture site. Scoring 1 point for each positive criterion, a total
      score of 4 predicts flexion injury with 100% sensitivity and 96.9% specificity.
      Score of 5 has 83.3% sensitivity and 100% specificity. CONCLUSION: Flexion
      hangman's injury can be diagnosed by the presence of four out of seven
      radiological criteria in the newly introduced scoring system. The authors believe
      that this method may help spinal surgeons in their selection of therapeutic
      strategy. Advances in knowledge: This study introduces fast, simple and more
      objective imaging criteria for the diagnosis of flexion hangman's injury and
      separates it from the non-flexion pattern.

PMID- 27885838
TI  - Osimertinib for EGFR T790M mutation-positive non-small cell lung cancer.
AB  - INTRODUCTION: Significant advances have been made since the development of
      epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting
      EGFR mutations in non-small-cell lung cancer (NSCLC), however, lung cancer cells
      eventually acquire resistance to those agents. Osimertinib (AZD9291) has been
      developed as 3rd generation EGFR-TKI with activities against sensitizing
      mutations and T790 M resistance mutation, which account for about 50% of the
      mechanisms of acquired resistance to 1st or 2nd generation EGFR-TKIs. A recent
      phase I/II clinical trial with osimertinib for advanced NSCLC patients with known
      sensitizing EGFR mutations and documented disease progression on prior EGFR-TKIs
      revealed promising effect with acceptable toxicities. Areas covered: This article
      summarizes current understanding and available preclinical and clinical data on
      osimertinib and also discusses future directions. The literature search included
      PubMed and the latest articles from international conferences. Expert commentary:
      The development of osimertinib has provided new therapeutic options for NSCLC
      patients harboring T790 M. Compared with other EGFR-TKIs including rociletinib,
      osimertinib seems to possess an advantage with respect to the effect and safety
      profile among existing EGFR-TKIs. However, tumor progression still occurs even
      when treating with osimertinib. A further understanding of the mechanisms of
      resistance is eagerly anticipated in order to develop next generation EGFR-TKIs.

PMID- 27885839
TI  - The association of plasma miR-155 and VCAM-1 levels with coronary collateral
      circulation.
AB  - AIM: Inflammation plays an important role in development of coronary collateral
      circulation (CCC). The aim of this study is to determine whether the inflammation
      related miRNA miR-155 and the inflammation marker VCAM-1 could be a biomarker for
      CCC. PATIENTS & METHODS: We measured levels of plasma VCAM-1 and miR-155 in
      patients with CCC according to Rentrop grade by ELISA or real-time polymerase
      chain reaction, respectively (n = 112). RESULTS: Plasma miR-155 was negatively
      correlated with VCAM-1 in the poor CCC group and with Rentrop grade in all
      patients with CCC. In addition, plasma VCAM-1 was significantly decreased in CAD
      patients with CCC. CONCLUSION: Plasma miR-155 might be a potent independent
      predictor of collateral formation.

PMID- 27885840
TI  - Factors associated with the reduction of albumin excretion in diabetic
      hypertensive patients: differential effect of manidipine versus amlodipine.
AB  - AIMS: In AMANDHA trial, the addition of manidipine, but not amlodipine, in
      diabetic patients with uncontrolled hypertension, microalbuminuria and preserved
      renal function resulted in a large decrease of urinary albumin excretion (UAE)
      despite similar blood pressure (BP) reductions. Factors associated with the
      reduction of UAE were analyzed. METHODS: For this purpose, a multivariable
      analysis was performed. RESULTS: Although after 6 months of treatment, manidipine
      and amlodipine decreased BP to a similar extent, reductions of UAE were higher
      with manidipine. The assigned treatment, changes in mean BP, sympathetic tone and
      glycemic control were associated with changes in UAE. CONCLUSION: The assigned
      treatment, changes in mean BP, sympathetic tone and glycemic control were
      independently associated with changes in UAE. Compared with amlodipine,
      manidipine reduced UAE to a higher extent, independently of BP reduction.

PMID- 27885841
TI  - The utility of saliva for the assessment of anti-pneumococcal antibodies:
      investigation of saliva as a marker of antibody status in serum.
AB  - CONTEXT: Salivary antibodies may act as non-invasive marker of systemic immunity
      enabling assessment of vaccination and protection against bacterial infections.
      OBJECTIVE: To assess if levels of anti-pneumococcal (Pn) antibodies in saliva
      reflect concentrations in serum and determine whether saliva can accurately
      identify protective concentrations in serum. METHODS: IgG, IgA and IgM antibody
      levels in paired saliva and serum samples were measured against 12 Pn
      polysaccharide antigens in 72 healthy adults. RESULTS: Antibody levels in saliva
      correlated positively with serum across immunoglobulin classes, most strongly for
      IgA. Individuals who had protective antibody levels in serum demonstrated
      significantly higher IgG and IgA salivary antibody concentrations/secretion
      rates. Salivary IgG and IgA Pn antibodies were able to distinguish between those
      with/without protective levels in serum for the majority of serotypes. Salivary
      IgM antibodies were not able to differentiate protective status. Median IgG and
      IgA Pn salivary parameters were able to identify individuals who had protective
      levels in serum on >=8/12 serotypes with moderate accuracy: median IgA secretion
      rates provided the best sensitivity (73%) and specificity (71%). CONCLUSIONS:
      These findings suggest that IgG and IgA Pn specific antibodies in saliva may be
      useful surrogate markers of antibody status in serum.

PMID- 27885842
TI  - Crucial role of noncoding RNA in driving prostate cancer development and
      progression.

PMID- 27885843
TI  - Current evaluation and management of anemia in patients with inflammatory bowel
      disease.
AB  - INTRODUCTION: Anemia is a common extraintestinal manifestation in IBD patients
      and considerably impacts disease prognosis, hospitalization rates and time lost
      from work. While iron deficiency anemia is predominant, combinations of
      hematimetric and biochemical markers enable detection and targeted therapy of
      other etiologies including vitamin B12/folic acid deficiencies, hemolysis,
      myelosuppression and pharmacotherapies. Areas covered: Current literature was
      searched for articles focusing on etiology, diagnostics and therapy of anemia in
      IBD. In the light of their own experience, the authors describe the physiology of
      anemia in IBD and present current evidence endorsing diagnostic and therapeutic
      options, focusing particularly on non-iron-related etiologies. Expert commentary:
      Anemia in IBD is polyetiological, reaching far beyond iron deficiency anemia.
      While clinicians need to be aware of the increasing pallet of diagnostic tools
      and therapeutic options, detailed studies are needed to develop more convenient
      test procedures, long-term treatment and monitoring strategies, and unified
      guidelines for daily practice.

PMID- 27885844
TI  - Guidance to manage inappropriate polypharmacy in older people: systematic review
      and future developments.
AB  - INTRODUCTION: Single disease state led evidence-based guidelines do not provide
      sufficient coverage of issues of multimorbidities, with the cumulative impact of
      recommendations often resulting in overwhelming medicines burden. Inappropriate
      polypharmacy increases the likelihood of adverse drug events, drug interactions
      and non-adherence. Areas covered: A detailed description of a pan-European
      initiative, 'Stimulating Innovation Management of Polypharmacy and Adherence in
      the Elderly, SIMPATHY', which is a project funded by the European Commission to
      support innovation across the European Union. This includes a systematic review
      of the literature aiming to summarize and review critically current policies and
      guidelines on polypharmacy management in older people. The policy driven,
      evidence-based approach to managing inappropriate polypharmacy in Scotland is
      described, with consideration of a change management strategy based on Kotter's
      eight step process for leading sustainable change. Expert opinion: The challenges
      around promoting appropriate polypharmacy are on many levels, primarily clinical,
      organisational and political, all of which any workable solution will need to
      address. To be effective, safe and efficient, any programme that attempts to deal
      with the complexities of prescribing in this population must be patient-centred,
      clinically robust, multidisciplinary and designed to fit into the healthcare
      system in which it is delivered.

PMID- 27885847
TI  - Receptor-specific TRAIL as a means to achieve targeted elimination of activated
      hepatic stellate cells.
AB  - Activated hepatic stellate cells (HSCs) are known to play a central role in liver
      fibrosis and their elimination is a crucial step toward the resolution and
      reversion of liver fibrosis. Tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) is a molecule that may contribute to the apoptotic removal of
      activated HSC through binding to its dedicated receptors. In the present study,
      we investigated the potential application of recombinant receptor-specific TRAIL
      proteins in the efficient elimination of activated HSCs. Our finding revealed
      differential contribution of TRAIL receptors among HSCs populations with
      activated hepatic stellate cells expresses more TRAIL receptors DR5. In vitro
      treatment of activated HSCs with DR5-specific or wild-type TRAIL variants induced
      a significant reduction in viability and extracellular matrix production, whereas
      no significant decrease in viability was associated with the treatment of cells
      by DR4-specific TRAIL. Our analysis indicate the successful application of the
      DR5 receptor-specific TRAIL variant in the targeted elimination of activated HSCs
      via interference with collagen production and simultaneous induction of apoptosis
      via activation of the caspase pathway. DR5 receptor-specific TRAIL may thus
      represent a new therapeutic compound for the treatment of liver fibrosis.

PMID- 27885846
TI  - Big endothelin-1 level is a useful marker for predicting the presence of isolated
      coronary artery ectasia.
AB  - CONTEXT: Endothelin-1(ET-1) has been implicated in coronary artery disease (CAD)
      and may be associated with coronary artery ectasia (CAE). OBJECTIVE: To clarify
      the relationship between big ET-1 and isolated CAE. METHODS: We measured big ET-1
      with ELISA in 216 patients (CAE, n = 72; CAD, n = 72; normal, n = 72) and
      evaluated the link with isolated CAE. RESULTS: The level of plasma big ET-1 was
      significantly higher in patients with isolated CAE (p < 0.001). Big ET-1 was
      strongly and independently associated with CAE by multivariate analysis (OR
      95%CI: 1.026 (1.018-1.034), p = 0.000). CONCLUSIONS: Big ET-1 may be a useful
      predictor for the presence of isolated CAE.

PMID- 27885848
TI  - Conveying a newly designed hydrophilic anti-human thymidylate synthase peptide to
      cisplatin resistant cancer cells: are pH-sensitive liposomes more effective than
      conventional ones?
AB  - CONTEXT: LR-peptide, a novel hydrophilic peptide synthetized and characterized in
      previous work, is able to reduce the multi-drug resistance response in cisplatin
      (cDPP) resistant cancer cells by inhibiting human thymidylate synthase (hTS)
      overexpressed in several tumors, including ovarian and colon-rectal cancers, but
      it is unable to enter the cells spontaneously. OBJECTIVE: The aim of this work
      was to design and characterize liposomal vesicles as drug delivery systems for
      the LR peptide, evaluating the possible benefits of the pH-responsive feature in
      improving intracellular delivery. MATERIALS AND METHODS: For this purpose,
      conventional and pH-sensitive liposomes were formulated, compared regarding their
      physical-chemical properties (size, PDI, morphology, in vitro stability and drug
      release) and studied for in vitro cytotoxicity against a cDDP-resistant cancer
      cells. RESULTS AND DISCUSSION: Results indicated that LR peptide was successfully
      encapsulated in both liposomal formulations but at short incubation time only LR
      loaded pH-sensitive liposomes showed cell inhibition activity while for long
      incubation time the two kinds of liposomes demonstrated the same efficacy.
      CONCLUSIONS: Data provide evidence that acidic pH-triggered liposomal delivery is
      able to significantly reduce the time required by the systems to deliver the drug
      to the cells without inducing an enhancement of the efficacy of the drug.

PMID- 27885849
TI  - DNA methylation at diagnosis is associated with response to disease-modifying
      drugs in early rheumatoid arthritis.
AB  - AIM: A proof-of-concept study to explore whether DNA methylation at first
      diagnosis is associated with response to disease-modifying antirheumatic drugs
      (DMARDs) in patients with early rheumatoid arthritis (RA). PATIENTS & METHODS:
      DNA methylation was quantified in T-lymphocytes from 46 treatment-naive patients
      using HumanMethylation450 BeadChips. Treatment response was determined in 6
      months using the European League Against Rheumatism (EULAR) response criteria.
      RESULTS: Initial filtering identified 21 cytosine-phosphate-guanines (CpGs) that
      were differentially methylated between responders and nonresponders. After
      conservative adjustment for multiple testing, six sites remained statistically
      significant, of which four showed high sensitivity and/or specificity (>=75%) for
      response to treatment. Moreover, methylation at two sites in combination was the
      strongest factor associated with response (80.0% sensitivity, 90.9% specificity,
      AUC 0.85). CONCLUSION: DNA methylation at diagnosis is associated with disease
      modifying antirheumatic drug treatment response in early RA.

PMID- 27885850
TI  - Detour sign in the diagnosis of subluxation of the long head of the biceps tendon
      with arthroscopic correlation.
AB  - OBJECTIVE: To determine whether detection of the detour sign via MRI indicates
      subluxation of the long head of the biceps tendon (SLBT) in the shoulder joint
      and to investigate the association of SLBT with the degeneration of the long head
      of the biceps tendon (LBT) and rotator cuff tears. METHODS: This retrospective
      study included 65 patients with shoulder pain who underwent shoulder MRI and
      arthroscopic surgery. When axial images revealed that the LBT was displaced over
      the inner rim of the bicipital groove with some remaining contact with the groove
      (Criterion 1), or demonstrated a "detour sign" of the biceps tendon (Criterion
      2), the lesion was diagnosed as an SLBT. Shoulder arthroscopy was used as the
      reference standard. RESULTS: Arthroscopy identified SLBT in 18 patients. When the
      MRI diagnosis was based on Criterion 1 alone, SLBT was diagnosed with a
      sensitivity of 44.4-55.6% and 75.4-80% accuracy. However, when the MRI diagnosis
      was based on Criteria 1 plus 2, SLBT was diagnosed with a sensitivity of 83.3
      94.4% and 78.5-81.5% accuracy. There was a significant difference (p < 0.05) in
      the diagnostic sensitivity of Criteria 1 and 2. CONCLUSION: The detour sign based
      on axial MRI may be regarded an additional useful anatomical feature that
      improves the diagnostic performance of MRI in the identification of SLBT lesions.
      Advances in knowledge: Recognition of the detour sign may enhance the diagnostic
      performance of the conventional MRI protocol over the MR arthrography protocol
      for SLBT.

PMID- 27885845
TI  - DNA methylation in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a systemic autoimmune disease facilitated
      by aberrant immune responses directed against cells and tissues, resulting in
      inflammation and organ damage. In the majority of patients, genetic
      predisposition is accompanied by additional factors conferring disease
      expression. While the exact molecular mechanisms remain elusive, epigenetic
      alterations in immune cells have been demonstrated to play a key role in disease
      pathogenesis through the dysregulation of gene expression. Since epigenetic marks
      are dynamic, allowing cells and tissues to differentiate and adjust, they can be
      influenced by environmental factors and also be targeted in therapeutic
      interventions. Here, we summarize reports on DNA methylation patterns in SLE,
      underlying molecular defects and their effect on immune cell function. We discuss
      the potential of DNA methylation as biomarker or therapeutic target in SLE.

PMID- 27885851
TI  - Is anti-inflammatory radiotherapy an effective treatment in trochanteritis?
AB  - OBJECTIVE: To evaluate the analgesic efficacy of low-dose radiotherapy in
      refractory cases of trochanteritis. METHODS: We evaluated a total of 60
      consecutive patients who received low-dose radiotherapy to achieve an anti
      inflammatory and analgesic effect for recurrent trochanteritis following scarce
      response to conventional therapy. All patients were evaluated at baseline (prior
      to radiotherapy) and at 1 and 4 months after radiotherapy and then yearly
      thereafter for pain assessment using a visual analogue scale (VAS) and to
      determine the administration of analgesic treatment. RESULTS: An improvement in
      the symptomatology was observed in 62% of the patients with a significant
      reduction in the VAS (8 +/- 2 vs 4 +/- 2; p < 0.0001), which was largely
      maintained until the second evaluation at 4 months. In the cases responding to
      radiotherapy, the probability of maintaining improvement beyond 24 months was
      70%. CONCLUSION: Low-dose anti-inflammatory radiation may be used in the
      treatment of the recurrent cases of relapse or no response of trochanteritis to
      conventional treatments, with a high probability of remission of pain. These
      preliminary results indicate the need for evaluating the use of radiotherapy in
      patients with trochanteritis refractory to conventional treatment in a long-term
      controlled study. Advances in knowledge: Radiotherapy provides effective
      analgesic treatment for patients refractory to standard treatment for
      trochanteritis.

PMID- 27885852
TI  - Video-assisted thoracic surgery techniques for lung cancer: which is better?

PMID- 27885854
TI  - Gossypibomas, a surgeon's nightmare-patient demographics, risk factors, imaging
      and how we can prevent it.
AB  - OBJECTIVE: Gossypibomas are a cottonoid matrix left behind following surgery.
      Owing to the legal issues associated with it, very few literature studies are
      available online, most of them being case reports. The purpose of our study was
      to identify the patient demographics, risk factors and imaging features. METHODS:
      Six surgically identified and histopathologically confirmed cases of gossypibomas
      recorded over a period of 5 years from a single tertiary institution were
      retrospectively evaluated for patient demographics [sex, age, body mass index
      (BMI)], type of surgery and duration from time of surgery to onset of symptoms.
      Ultrasound and CT images obtained from our hospital database were evaluated for
      their characteristic pattern. Statistics used included percentage and frequency.
      RESULTS: Females formed the bulk of our patients and the mean BMI of our patients
      was 24.25. The interval between surgery and symptom presentation ranged from 2
      months to 7 years. The most common imaging patterns observed on ultrasound and CT
      were a thick-walled hypoechoic lesion with a strong posterior acoustic shadowing
      and a "spongiform pattern", respectively. CONCLUSION: A detailed patient history,
      taking into account radiologist-surgeon interaction, along with familiarization
      of the various risk factors and imaging patterns can bring about an accurate
      diagnosis of a gossypiboma. Advances in knowledge: Our study showed that the
      female sex, especially those undergoing gynaecology-related surgery such as
      hysterectomy and patients with a high BMI were at risk of gossypibomas. The
      combination of a hypoechoic lesion with strong posterior shadowing on ultrasound
      along with a spongiform pattern on CT was highly characteristic for gossypiboma
      on imaging.

PMID- 27885853
TI  - Nomogram for radiation-induced hypothyroidism prediction in nasopharyngeal
      carcinoma after treatment.
AB  - OBJECTIVE: The aim of this study was to develop a nomogram for radiation-induced
      hypothyroidism (RHT) prediction. METHODS: We collected data from 164 patients
      with nasopharyngeal carcinoma (NPC) in our previous prospective study.
      Biochemical hypothyroidism was defined as a serum thyroid-stimulating hormone
      level greater than the normal value. We collected both clinical and dose-volume
      factors. A univariate Cox regression analysis was performed to identify RHT risk
      factors. Optimal predictors were selected according to the least absolute
      shrinkage and selection operator (LASSO). We then selected the Cox regression
      models that best balanced the prediction performance and practicability to build
      a nomogram for RHT prediction. RESULTS: There were 38 (23.2%) patients who
      developed RHT, and the median follow-up was 24 months. The univariate Cox
      regression analysis indicated that gender, minimum dose, mean dose (Dmean) and
      V25-V60 [Vx (%), the percentage of thyroid volume receiving >x Gy] of the thyroid
      were significantly associated with RHT. The variables of gender, receiving
      chemotherapy or not (chemo), Dmean and V50 were selected using the LASSO
      analysis. A nomogram based on a three-variable (gender, chemo and V50) Cox
      regression model was constructed, and its concordance index was 0.72. Good
      accordance between prediction and observation was showed by calibration curves in
      the probability of RHT at 18, 24 and 30 months. CONCLUSION: This study built a
      nomogram for RHT in NPC survivors by analyzing both clinical and dose-volume
      parameters using LASSO. Thus, the individual dose constraint could be achieved in
      a visual format. Advances in knowledge: This study used LASSO to more accurately
      address the multicollinear problem between variables. The resulting nomogram will
      help physicians predict RHT.

PMID- 27885855
TI  - Frameless stereotactic volumetric modulated arc radiotherapy of brachial plexus
      tumours in dogs: 10 cases.
AB  - OBJECTIVE: Treatment of canine peripheral nerve sheath tumours (PNSTs) is
      challenging and prognosis after surgical resection is considered poor. The aim of
      this study was to evaluate the feasibility and effectiveness of stereotactic
      radiotherapy (RT) of these tumours. METHODS: 10 dogs with clinical symptoms and
      MRI findings consistent with PNSTs of the brachial plexus, branches and nerve
      roots were treated with linear accelerator-based volumetric-modulated arc
      radiotherapy (VMAT) with a dose of 35 Gy/5 fractions. Clinical and MRI follow-up
      examinations were planned and radiotoxicity and survival times were investigated.
      RESULTS: Tumours involved the plexus and proximal nerves in three dogs, the
      plexus, proximal nerves and nerve roots in five dogs and the nerve roots and
      proximal nerves in two dogs. Partial response and partial or complete reductions
      of neurological deficits were observed in all the treated dogs. Local recurrence
      was observed in 9/10 of treated dogs. No symptom directly referable to
      radiotoxicity was observed. Mean overall survival of 371 +/- 30 days [95%
      confidence interval (CI) of (315-427)] and mean progression-free survival of 240
      +/- 30 days (95% CI of 188-291) from this work are comparable with surgical
      literature data regarding the plexus and proximal nerve localization, but are
      superior in comparison with nerve root localization. CONCLUSION: VMAT can be a
      safe and viable alternative to surgery in cases of canine brachial plexus PNSTs
      involving the proximal nerves and nerve roots. Advances in knowledge: To our
      knowledge, this is the first prospective observational clinical study regarding
      VMAT stereotactic RT treatment for canine brachial plexus PNSTs and suggests that
      VMAT may achieve at least similar clinical outcome than surgery in a safer way.

PMID- 27885856
TI  - Ankle impingement syndromes: an imaging review.
AB  - Ankle impingement syndromes encompass a broad spectrum of post-traumatic and
      chronic degenerative changes that present with pain on specific movements about
      the ankle joint. Both amateur and professional athletes are disproportionately
      affected by these conditions, and while conservative measures can potentially
      treat an impingement syndrome, definitive therapy is often alleviated surgically.
      Imaging (including conventional radiography, ultrasound, CT and MRI) plays an
      invaluable role in the diagnosis and pre-surgical work-up. An anatomically based
      classification system is useful in these syndromes, as the aetiology, sites of
      pathology and preferred treatment methods are similarly based on anatomic
      locations about the ankle. This review focuses on the anatomic locations,
      pathophysiology, imaging considerations and brief discussion of therapies for
      each of the major anatomic ankle impingement syndromes.

PMID- 27885857
TI  - Dosimetric trade-offs in breast treatment with VMAT technique.
AB  - OBJECTIVE: Breast planning with volumetric modulated arc therapy (VMAT) has been
      explored, especially for left-sided breast treatments, with the primary intent of
      lowering the heart dose and improving target dose homogeneity. As a trade-off,
      larger healthy tissue volumes would receive low dose levels, with the potential
      risk of increasing late toxicities and secondary cancer induction, although no
      clinical data are available today to confirm the risk level. The scope of this
      work is to explore the dosimetric trade-offs using two different VMAT plans.
      METHODS: Two planning strategies for dual-partial-arc VMAT, RA_avoid and RA_full,
      with and without avoidance sectors, were explored in a cohort of 20 patients, for
      whole left breast irradiation for 40.05 Gy to the mean target dose in 15
      fractions. Common dose objectives included a stringent dose homogeneity, mean
      dose to the heart <5 Gy, ipsilateral lung (Ilung) <8 Gy, contralateral lung
      (Clung) <2 Gy and contralateral breast (Cbreast) <3 Gy. RESULTS: RA_full showed a
      better dose conformity, lower high-dose spillage in the healthy tissue and lower
      skin dose. RA_avoid presented a reduction of the mean doses for all critical
      structures: 51% to the heart, 12% to the Ilung, 81% to the Clung and 73% to the
      Cbreast. All differences were significant with p < 0.0001. CONCLUSION: The
      adaptation of VMAT options to planning objectives reduced significantly the
      healthy tissue dose levels at the price of some high-dose spillage. Evaluation of
      the trade-offs for application to the different critical structures should drive
      in improving the usage of the VMAT technique for breast cancer treatment.
      Advances in knowledge: Different planning strategies in the same VMAT technique
      could give significant variations in dose distributions. The choice of the trade
      offs would affect the possible future late toxicity and secondary cancer
      induction risk.

PMID- 27885859
TI  - Effect of 8 months of whole-body vibration training on quality of life in elderly
      women.
AB  - Whole-body vibration (WBV) training in elderly may improve muscle strength,
      muscle power and postural control. However, knowledge about the effect of WBV
      training in elderly on measures of health as a multidimensional construct (health
      related quality of life, HRQoL) is scarce. The present study aimed to determine
      the effects of WBV training on HRQoL in elderly women. A total of 37 women (aged
      82.4 +/- 5.7 years) were recruited and were assigned to either the WBV group or
      to the control (CON) group. After 8 months of training, the WBV group showed non
      significant changes on HRQoL and additional health-related outcomes (fall risk,
      life satisfaction or cognitive status). Our findings are in disagreement with
      previous studies of shorter duration (6 weeks), which reported positive
      significant changes in HRQoL in elderly people. Discrepancies among studies may
      be partly attributed to methodological differences, but the existence of
      publication bias in previous studies cannot be discarded.

PMID- 27885858
TI  - A systematic review of outcomes following stereotactic ablative radiotherapy in
      the treatment of early-stage primary lung cancer.
AB  - Stereotactic ablative body radiotherapy (SABR) describes a radiotherapy (RT)
      technique where high doses of radiation are precisely delivered to an
      extracranial target within the body, using either a single fraction of RT or
      using multiple small numbers of fractions. SABR has now become the standard of
      care treatment for patients with early-stage non-small-cell lung cancer (NSCLC)
      for whom surgery is not appropriate. This systematic review considers the
      evidence supporting the use of SABR in early-stage NSCLC, reported toxicity
      rates, the use of SABR in centrally located NSCLC, the use of SABR as salvage
      therapy following surgery or RT, and future potential drug combinations with
      SABR.

PMID- 27885860
TI  - Pioglitazone for the treatment of Alzheimer's disease.
AB  - INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia in
      the elderly. Pharmacological treatment of AD includes Anticholinesterase
      Inhibitors (AChEIs) for mild-moderate AD, and memantine for severe AD. These
      drugs provide mainly symptomatic short-term benefits without clearly influencing
      the progression of the disease. Pioglitazone (AD4833) is an insulin sensitizer of
      the thiazolidinedione class of nuclear Peroxisome-Proliferator Activated Receptor
      gamma (PPARgamma) agonists. It binds to PPARgamma, affecting gene transcription
      and reducing inflammation. Areas covered: This review discusses the history of
      Pioglitazone, its pharmacokinetics and pharmacodynamics profile, and safety
      issues, together with an overview of clinical trials carried out so far. A
      literature search was made in Pubmed for pioglitazone, AD, trial, and on the
      ClinicalTrials.gov site for clinical trials with Pioglitazone. Expert opinion: A
      Phase II study in AD, and its previous indication for diabetes, showed that
      Pioglitazone is safe and well tolerated. So far, two large Phase III trials are
      ongoing, but there are no preliminary results yet on a possible beneficial effect
      on cognition in patients with AD.

PMID- 27885861
TI  - Additional synthesis on thiophene-containing trisubstituted methanes (TRSMs) as
      inhibitors of M. tuberculosis and 3D-QSAR studies.
AB  - We earlier reported thiophene-containing trisubstituted methanes (TRSMs) as novel
      cores carrying anti-tubercular activity, and identified S006-830 as the
      phenotypic lead with potent bactericidal activity against single- and multi-drug
      resistant clinical isolates of Mycobacterium tuberculosis (M. tb). In this work,
      we carried out additional synthesis of several TRSMs. The reaction scheme
      essentially followed the Grignard reaction and Friedel-Crafts alkylation,
      followed by insertion of a dialkylaminoethyl chain. We also performed
      microbiological evaluations including in vitro screening against the virulent
      strain M. tb H37Rv, cytotoxicity assessment in the Vero C-1008 cell line, and 3D
      QSAR studies with comparative molecular field analysis (CoMFA) and comparative
      molecular similarity index analysis (CoMSIA). CoMFA and CoMSIA models yielded
      good statistical results in terms of q2 and r2 values, suggesting the validity of
      the models. It was concluded that a para-substituted benzene ring with bulkier
      electron-donating groups and aminoalkyl chains are required for higher inhibitory
      capacity against M. tuberculosis. We believe that these insights will rationally
      guide the design of newer, optimal, TRSMs.

PMID- 27885862
TI  - An automated curation procedure for addressing chemical errors and
      inconsistencies in public datasets used in QSAR modelling.
AB  - The increasing availability of large collections of chemical structures and
      associated experimental data provides an opportunity to build robust QSAR models
      for applications in different fields. One common concern is the quality of both
      the chemical structure information and associated experimental data. Here we
      describe the development of an automated KNIME workflow to curate and correct
      errors in the structure and identity of chemicals using the publicly available
      PHYSPROP physicochemical properties and environmental fate datasets. The workflow
      first assembles structure-identity pairs using up to four provided chemical
      identifiers, including chemical name, CASRNs, SMILES, and MolBlock. Problems
      detected included errors and mismatches in chemical structure formats,
      identifiers and various structure validation issues, including hypervalency and
      stereochemistry descriptions. Subsequently, a machine learning procedure was
      applied to evaluate the impact of this curation process. The performance of QSAR
      models built on only the highest-quality subset of the original dataset was
      compared with the larger curated and corrected dataset. The latter showed
      statistically improved predictive performance. The final workflow was used to
      curate the full list of PHYSPROP datasets, and is being made publicly available
      for further usage and integration by the scientific community.

PMID- 27885863
TI  - Progress and pitfalls in finding the 'missing proteins' from the human proteome
      map.
AB  - INTRODUCTION: The Human Proteome Project was launched with two main goals: the
      comprehensive and systematic definition of the human proteome map and the
      development of ready to use analytical tools to measure relevant proteins in
      their biological context in health and disease. Despite the great progress in
      this endeavour, there is still a group of reluctant proteins with no, or scarce,
      experimental evidence supporting their existence. These are called the 'missing
      proteins' and represent one of the biggest challenges to complete the human
      proteome map. Areas covered: This review focuses on the description of the
      missing proteome based on the HUPO standards, the analysis of the reasons
      explaining the difficulty of detecting missing proteins and the strategies
      currently used in the search for missing proteins. The present and future of the
      quest for the missing proteins is critically revised hereafter. Expert
      commentary: An overarching multidisciplinary effort is currently being done under
      the HUPO umbrella to allow completion of the human proteome map. It is expected
      that the detection of missing proteins will grow in the coming years since the
      methods and the best tissue/cell type sample for their search are already on the
      table.

PMID- 27885864
TI  - Probabilistic treatment planning for pancreatic cancer treatment: prospective
      incorporation of respiratory motion shows only limited dosimetric benefit.
AB  - BACKGROUND: We introduced a probabilistic treatment planning approach that
      prospectively incorporates respiratory-induced motion in the treatment plan
      optimization. The aim of this study was to determine the potential dosimetric
      benefit by comparing this approach to the use of an internal target volume (ITV).
      MATERIAL AND METHOD: We retrospectively compared the probabilistic respiratory
      motion-incorporated (RMI) approach to the ITV approach for 18 pancreatic cancer
      patients, for seven simulated respiratory amplitudes from 5 to 50 mm in the
      superior-inferior (SI) direction. For each plan, we assessed the target coverage
      (required: D98%>=95% of 50 Gy prescribed dose). For the RMI plans, we
      investigated whether target coverage was robust against daily variations in
      respiratory amplitude. We determined the distance between the clinical target
      volume and the 30 Gy isodose line (i.e. dose gradient steepness) in the SI
      direction. To investigate the clinical benefit of the RMI approach, we created
      for each patient an ITV and RMI treatment plan for the three-dimensional (3D)
      respiratory amplitudes observed on their pretreatment 4D computed tomography
      (4DCT). We determined Dmean, V30Gy, V40Gy and V50Gy for the duodenum. RESULTS:
      All treatment plans yielded good target coverage. The RMI plans were robust
      against respiratory amplitude variations up to 10 mm, as D98% remained >=95%. We
      observed steeper dose gradients compared to the ITV approach, with a mean
      decrease from 25.9 to 19.2 mm for a motion amplitude of 50 mm. For the 4DCT
      motion amplitudes, the RMI approach resulted in a mean decrease of 0.43 Gy, 1.1
      cm3, 1.4 cm3 and 0.9 cm3 for the Dmean, V30Gy, V40Gy and V50Gy of the duodenum,
      respectively. CONCLUSION: The probabilistic treatment planning approach yielded
      significantly steeper dose gradients and therefore significantly lower dose to
      surrounding healthy tissues than the ITV approach. However, the observed
      dosimetric gain for clinically observed respiratory motion amplitudes for this
      patient group was limited.

PMID- 27885865
TI  - Delivering phage therapy per os: benefits and barriers.
AB  - INTRODUCTION: Multidrug-resistant bacterial infections of the gastrointestinal
      tract pose a serious public health concern. High levels of antibiotic drug
      resistance, along with the potential for antibiotics to precipitate disease or
      alter the gut microbiome has prompted research into alternative treatment
      methods. Evidence suggests that bacteriophage therapy delivered per os may be
      well-suited to target such infections. Areas covered: Herein, we discuss the
      specific advantages and challenges of using orally administered phage therapy.
      Our literature review encompasses recent works using phages to target various
      clinically-relevant bacteria in vivo. We also provide insights into methods that
      aim to overcome the barriers to effective phage transit through the harsh
      gastrointestinal environment. Expert commentary: Evidence from a number of in
      vivo animal studies suggests that targeting bacterial infections using phages
      delivered orally holds potential. Efficacious oral phage therapy depends on the
      delivery of sufficient phage titers to the infection site, which may be hindered
      by the host's gastrointestinal tract and immune response.

PMID- 27885866
TI  - Thymic-derived tolerizing dendritic cells are upregulated in the spleen upon
      treatment with intravenous immunoglobulin in a murine model of immune
      thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by
      low platelet counts. First-line treatment includes intravenous immunoglobulin
      (IVIg), however, its working mechanism remains incompletely understood. We
      investigated splenic and thymic dendritic cell (DC) subsets upon IVIg treatment
      in a well-characterized active murine model of ITP. During active disease, there
      was a significant peripheral deficiency of splenic tolerizing SIRPalpha+ DCs
      which could be rescued by IVIg therapy, increasing platelet counts. These splenic
      tolerizing DC changes were associated with an abrogation of the thymic-retention
      of tolerizing DCs, suggesting that IVIg may raise platelet counts in ITP by
      modulating peripheral numbers of tolerizing DCs.

PMID- 27885867
TI  - Protein corona modulation of hepatocyte uptake and molecular mechanisms of gold
      nanoparticle toxicity.
AB  - Protein corona formation over gold nanoparticles (AuNP) can modulate cellular
      responses by altering AuNP physicochemical properties. The liver plays an
      essential role in metabolism, detoxification and elimination of xenobiotics and
      drugs as well as circulating NP clearance. We investigated human hepatic uptake
      of 40 and 80 nm AuNP with branched polyethylenimine (BPEI), lipoic acid (LA) and
      polyethylene glycol (PEG) coatings as well as human plasma protein (HP) and human
      serum albumin (HSA) coronas. AuNP-mediated cytotoxicity, reactive oxygen/reactive
      nitrogen species (ROS/RNS), and CYP activity in human hepatocytes as well as
      molecular mechanisms with 40 nm bare and HP BPEI-AuNP were investigated. Time
      dependent increase in uptake occurred for all bare AuNP but HP and HSA decreased
      uptake except for 40 nm HP PEG-AuNP. BPEI-AuNP showed time-and concentration
      dependent increase in ROS/RNS which correlated with cytotoxicity at 24 h. HP
      corona substantially reduced ROS/RNS. The 40 and 80 nm bare, HP or HSA LA- and
      PEG-AuNP were not toxic but HP was as cytotoxic as bare BPEI-AuNP. All bare and
      HP BPEI-AuNP, except for HP 80 nm BPEI-AuNP toward CYP1A2, inhibited CYP1A2,
      CYP2C9 and CYP3A4 activity. Transcriptional profiling was dose-dependent with 40
      nm bare BPEI-AuNP (1.9% genes at IC10 and 18.9% at LC50) and HP (23.5% at LC50).
      Differentially expressed genes at LC50 were mainly involved in phase I metabolism
      and phospholipidosis pathways. Cytotoxicity of bare BPEI-AuNP caused an
      upregulation of antioxidant and pro-apoptotic genes. These studies contribute to
      a better understanding of the dramatic effect of protein coronas (PC) on AuNP
      cellular uptake, cytotoxicity and their underlying molecular mechanisms of
      action.

PMID- 27885868
TI  - A case report of iatrogenic cutaneous Kaposi sarcoma due to rituximab therapy for
      thrombotic thrombocytopenic purpura.

PMID- 27885869
TI  - Pre-market version of a commercially available hearing instrument with a tinnitus
      sound generator: feasibility of evaluation in a clinical trial.
AB  - OBJECTIVE: This report considers feasibility of conducting a UK trial of
      combination devices for tinnitus, using data from the study which evaluated
      different listener programmes available within the pre-market version of Oticon
      Alta with Tinnitus Sound Generator. DESIGN: Open and closed questions addressed
      the following feasibility issues: (1) Participant recruitment; (2) Device
      acceptability; (3) Programme preferences in different self-nominated listening
      situations; (4) Usability; (5) Compliance; (6) Adverse events. STUDY SAMPLE:
      Eight current combination hearing aid users (all males) aged between 62-72 years
      (mean age 67.25 years, SD = 3.8). RESULTS: All eight participants reported the
      physical aspects and noise options on the experimental device to be acceptable.
      Programmes with amplification and masking features were equally preferred over
      the basic amplification-only programme. Individual preferences for the different
      programme options varied widely, both across participants and across listening
      situations. CONCLUSIONS: A set of recommendations for future trials were
      formulated which calls for more "real world" trial design rather than tightly
      controlling the fitting procedure.

PMID- 27885870
TI  - Transanal total mesorectal excision for restorative coloproctectomy in an obese
      high-risk patient with colitis-associated carcinoma.
AB  - Transanal total mesorectal excision (TaTME) offers great potential for the
      treatment of malign and benign diseases. However, laparoscopic-assisted TaTME in
      ulcerative colitis has not been described in more than a handful of patients. We
      present a 47-year-old highly comorbid female patient with an ulcerative colitis
      associated carcinoma of the ascending colon and steroid- refractory pancolitis. A
      two-stage restorative coloproctectomy including right-sided complete mesocolic
      excision was conducted. The second step consisted of a successful nerve-sparing
      TaTME and a handsewn ileal pouch-anal anastomosis. TaTME may extend the possible
      treatment options in inflammatory bowel disease, especially for high-risk
      patients.

PMID- 27885871
TI  - Continuous prophylaxis with recombinant factor IX Fc fusion protein and
      conventional recombinant factor IX products: comparisons of efficacy and weekly
      factor consumption.
AB  - BACKGROUND: Continuous prophylaxis for patients with hemophilia B requires
      frequent injections that are burdensome and that may lead to suboptimal adherence
      and outcomes. Hence, therapies requiring less-frequent injections are needed. In
      the absence of head-to-head comparisons, this study compared the first extended
      half-life-recombinant factor IX (rFIX) product-recombinant factor IX Fc fusion
      protein (rFIXFc)-with conventional rFIX products based on annualized bleed rates
      (ABRs) and factor consumption reported in studies of continuous prophylaxis.
      METHODS: This study compared ABRs and weekly factor consumption rates in clinical
      studies of continuous prophylaxis treatment with rFIXFc and conventional rFIX
      products (identified by systematic literature review) in previously-treated
      adolescents and adults with moderate-to-severe hemophilia B. Meta-analysis was
      used to pool ABRs reported for conventional rFIX products for comparison.
      Comparisons of weekly factor consumption were based on the mean, reported or
      estimated from the mean dose per injection. RESULTS: Five conventional rFIX
      studies (injections 1 to >3 times/week) met the criteria for comparison with once
      weekly rFIXFc reported by the B-LONG study. The pooled mean ABR for conventional
      rFIX was slightly higher than but comparable to rFIXFc (difference=0.71; p =
      0.210). Weekly factor consumption was significantly lower with rFIXFc than in
      conventional rFIX studies (difference in means = 42.8-74.5 IU/kg/week [93-161%],
      p < 0.001). CONCLUSION: Comparisons of clinical study results suggest weekly
      injections with rFIXFc result in similar bleeding rates and significantly lower
      weekly factor consumption compared with more-frequently-injected conventional
      rFIX products. The real-world effectiveness of rFIXFc may be higher based on
      results from a model of the impact of simulated differences in adherence.

PMID- 27885872
TI  - Improvement of solubility, dissolution and stability profile of artemether solid
      dispersions and self emulsified solid dispersions by solvent evaporation method.
AB  - The purpose of this study was to investigate changes in the water solubility of
      artemether; a poorly soluble drug used for the treatment of malaria. Different
      solid dispersions (SDs) of artemether were prepared using artemether and
      polyethylene glycol 6000 at ratio 12:88 (Group 1), self-emulsified solid
      dispersions (SESDs) containing artemether, polyethylene glycol 6000, cremophor-A
      25, olive oil, hydroxypropylmethylcellulose and transcutol in the ratio
      12:75:5:4:2:2, respectively (Group 2). SESDs were also prepared by substituting
      cremophor-A-25 in Group 2 with poloxamer 188 (noted as Group 3). Each of these
      preparations was formulated using physical mixing and the solvent evaporation
      method. Aqueous solubility of artemether improved 11-, 95- and 102-fold, while
      dissolution (in simulated gastric fluid) increased 3-, 13- and 14-fold, for
      formulation groups 1, 2 and 3, respectively. X-ray diffraction patterns of SDs
      indicated a decrease in peak intensities at 10 degrees  implying reduced
      artemether crystallinity. Scanning electron micrographs invariably revealed
      embedment of artemether by various excipients and a glassy appearance for solvent
      evaporated mixtures for all three formulation Groups. Our findings indicate
      improved hydrophilic interactions for drug particles yield greater solubility and
      dissolution in the following order for artemether formulating methods: solvent
      evaporation mixtures > physical mixtures > pure artemether.

PMID- 27885873
TI  - Effects of artificial tracheal fixation on tracheal epithelial regeneration and
      prevention of tracheal stenosis.
AB  - CONCLUSION: Tight fixation of the artificial trachea is important for
      epithelialization and tracheal stenosis. OBJECTIVE: The authors have developed an
      artificial trachea and have used it for tracheal reconstruction. Although various
      studies on tracheal reconstruction have been conducted, no studies have examined
      the effect of artificial tracheal fixation on tracheal stenosis and regeneration.
      Therefore, the purpose of the present study was to evaluate the effect of
      artificial tracheal fixation. STUDY DESIGN: Preliminary animal experiment.
      METHODS: Artificial tracheae were implanted into rabbits with partial tracheal
      defects. Tracheal stenosis and regeneration of the tracheal epithelium on the
      artificial tracheae were evaluated by endoscopic examination, scanning electron
      microscopic analysis, and histological examination. The artificial tracheae fixed
      to the tracheal defects were classified into three groups (0-point, 4-point, and
      8-point) by the number of fixation points. RESULTS: At 14 and 28 days post
      implantation, the luminal surface of the implantation area was mostly covered
      with epithelium in all fixation groups. However, a small amount of granulation
      tissue was observed in the 0-point fixation group at 14 days post-implantation.
      Moreover, tracheal stenosis did not occur in the 8-point fixation group, but
      stenosis was detected in the other groups.

PMID- 27885875
TI  - Epigenomic therapies: the potential of targeting SIRT6 for the treatment of
      pancreatic cancer.

PMID- 27885876
TI  - Predictors and survival for pathologic tumor response grade in borderline
      resectable and locally advanced pancreatic cancer treated with induction
      chemotherapy and neoadjuvant stereotactic body radiotherapy.
AB  - BACKGROUND: Neoadjuvant therapy response correlates with survival in multiple
      gastrointestinal malignancies. To potentially augment neoadjuvant response for
      pancreas adenocarcinoma, we intensified treatment with stereotactic body
      radiotherapy (SBRT) following multi-agent chemotherapy. Using this regimen, we
      analyzed whether the College of American Pathology (CAP) tumor regression grade
      (TRG) at pancreatectomy correlated with established response biomarkers and
      survival. MATERIALS AND METHODS: We identified borderline resectable (BRPC) and
      locally advanced (LAPC) pancreatic cancer patients treated according to our
      institutional clinical pathway who underwent surgical resection with reported TRG
      (n = 81, median follow-up after surgery 24.2 months). Patients had baseline CA19
      9, computed tomography (CT), endoscopic ultrasound, and FDG positron emission
      tomography (PET)/CT then underwent multi-agent chemotherapy (79% with three
      cycles of gemcitabine, docetaxel and capecitabine) followed by 5-fraction SBRT.
      They then underwent restaging CT, PET/CT and CA19-9. Overall (OS) and progression
      free (PFS) survival were estimated and compared by Kaplan-Meier and log-rank
      methods. Univariate ordinal logistic regression correlated TRG with baseline,
      restaging and change in CA19-9 and the PET maximum standardized uptake value
      (SUVmax). RESULTS: Restaging level and decrease in CA19-9 correlated with
      improved TRG (p = .02 for both) as did restaging SUVmax (p < .01), yet there was
      no TRG correlation with decrease in SUVmax (p = .10) or CT response (p = .30).
      The TRG groups had similar OS and PFS except the TRG 0 (complete response) group.
      Compared to partial response levels (TRG 1-3, median OS 33.9 months, median PFS
      13.0 months), the six (7%) patients with TRG 0 had no deaths (p = .05) and only
      one progression (p = .03). A group of 10 (12%) TRG 1 patients with only residual
      isolated tumor cells had similar outcomes to the other TRG 1-3 patients.
      CONCLUSION: Pre-operative PET-CT and CA19-9 response correlate with
      histopathologic tumor regression. Patients with complete pathologic response have
      superior outcomes, suggesting a rationale for intensification and personalization
      of neoadjuvant therapy in BRPC and LAPC.

PMID- 27885877
TI  - Surgical outcomes of middle fossa approach in intracanalicular vestibular
      schwannoma.
AB  - CONCLUSION: Middle fossa approach (MFA) shows a hearing preservation rate of 86%
      and facial nerve function was preserved with HB grade I or II in 93%. MFA is a
      good treatment option for intra-canalicular vestibular schwannomas when surgical
      excision is needed. BACKGROUND: Surgical outcomes of vestibular schwannoma have
      progressively improved with the advancement of microsurgical instruments. MFA is
      known to have better chances to preserve hearing, while it has limited access to
      the posterior fossa, limitation of tumor size, and higher risk of post-operative
      facial nerve weakness. OBJECTIVES: To investigate surgical outcomes and clinical
      efficiency of MFA in vestibular schwannoma. METHODS: A retrospective study was
      done in 14 patients who underwent MFA for vestibular schwannoma in Asan Medical
      Center. RESULTS: The median age at diagnosis was 46.3 years. At initial
      presentation, 57% of the patients had vertigo, 43% hearing disturbance, and 64%
      tinnitus. The mean tumor size was 9.7 mm. The tumors were completely resected in
      86% of the patients. Hearing was post-operatively preserved in 12 patients and
      two patients lost their hearing following surgery. Facial nerve function post
      operatively remained unchanged in 12 patients (86%).

PMID- 27885874
TI  - Post-translational regulation of neuronal nitric oxide synthase: implications for
      sympathoexcitatory states.
AB  - INTRODUCTION: Nitric oxide (NO) synthesized via neuronal nitric oxide synthase
      (nNOS) plays a significant role in regulation/modulation of autonomic control of
      circulation. Various pathological states are associated with diminished nNOS
      expression and blunted autonomic effects of NO in the central nervous system
      (CNS) including heart failure, hypertension, diabetes mellitus, chronic renal
      failure etc. Therefore, elucidation of the molecular mechanism/s involved in
      dysregulation of nNOS is essential to understand the pathogenesis of increased
      sympathoexcitation in these diseased states. Areas covered: nNOS is a highly
      regulated enzyme, being regulated at transcriptional and posttranslational levels
      via protein-protein interactions and modifications viz. phosphorylation,
      ubiquitination, and sumoylation. The enzyme activity of nNOS also depends on the
      optimal concentration of substrate, cofactors and association with regulatory
      proteins. This review focuses on the posttranslational regulation of nNOS in the
      context of normal and diseased states within the CNS. Expert opinion: Gaining
      insight into the mechanism/s involved in the regulation of nNOS would provide
      novel strategies for manipulating nNOS directed therapeutic modalities in the
      future, including catalytically active dimer stabilization and protein-protein
      interactions with intracellular protein effectors. Ultimately, this is expected
      to provide tools to improve autonomic dysregulation in various diseases such as
      heart failure, hypertension, and diabetes.

PMID- 27885878
TI  - A systematic review of risks and benefits with nipple-areola-reconstruction.
AB  - BACKGROUND: Most women who have their breast reconstructed are offered NAC
      reconstruction. Nonetheless, it is unclear what scientific evidence there is for
      the procedure. The aims of the present systematic review were to evaluate the
      quality of evidence for benefits and risks with NAC reconstruction, and to
      examine the evidence for different techniques. METHODS: Relevant databases were
      searched. Inclusion criteria were controlled studies comprising >=20 patients and
      a case series of >=50 patients. Included articles had to meet criteria defined in
      a PICO (Patient, Intervention, Comparison, and Outcome). Data extraction and
      collection were performed according to the QUADAS tool. The level of evidence of
      the selected articles was assessed according to the Oxford Centre for Evidence
      Based Medicine 2009 guidelines, and total evidence for the different research
      questions was graded according to the GRADE-system. RESULTS: A total of 362
      abstracts were retrieved following the search. Of these 325 did not meet the
      inclusion criteria and were excluded, leaving 37 studies to be included in the
      review. Among these, 36 were case series and one a small randomised non-blinded
      study Conclusions: The existing quality of evidence for risks and benefits of the
      operation is very low. It is unclear what the complication frequencies are after
      the reconstruction, and what effect on quality-of-life the operation has.
      Prospective studies of high quality are needed to evaluate the health effects and
      risks with NAC reconstruction.

PMID- 27885879
TI  - A high preoperative carbohydrate antigen 19-9 level is a risk factor for
      recurrence in stage II colorectal cancer.
AB  - BACKGROUND: Many risk factors for recurrence in stage II colorectal cancer (CRC)
      have been proposed, and the efficacy of adjuvant chemotherapy is still
      controversial. This study aimed to identify risk factors for tumor recurrence and
      assess whether they are related to the benefits of adjuvant chemotherapy in stage
      II CRC. MATERIAL AND METHODS: Patients with stage II CRC that was curatively
      operated on in a tertiary hospital between 2005 and 2014 were analyzed. Cox's
      proportional hazards models were applied to identify risk factors for recurrence
      and overall mortality. Kaplan-Meier methods were used to evaluate whether
      adjuvant chemotherapy was beneficial in terms of recurrence-free survival (RFS).
      RESULTS: A total of 384 patients were identified, among whom 38 (10%) received
      adjuvant chemotherapy. In a median follow-up of 48.6 months, 52 patients (14%)
      developed recurrence. Multivariate analyses identified two independent parameters
      that significantly decreased RFS; pathological T4 [hazard ratio (HR), 2.34; 95%
      confidence interval (CI), 1.31-4.15; p = .0045) and preoperative carbohydrate
      antigen (CA) 19-9 > 37 U/ml (HR 1.96; 95% CI 1.02-3.58; p = .045). These factors
      also inversely correlated with overall survival; T4: HR 2.10, p = .019) and CA 19
      9 > 37 U/ml (HR 2.15, p = .025). The combination of T4 and CA 19-9 > 37 U/ml
      resulted in an increased HR (3.52) for recurrence. However, adjuvant chemotherapy
      did not improve RFS in patients with these features. CONCLUSION: The present
      study demonstrated elevated CA 19-9 levels as well as T4 independently predicted
      worse long-term outcomes in patients with stage II CRC. However, the
      characterization of patients who gain survival advantages by adjuvant
      chemotherapy requires further investigation.

PMID- 27885880
TI  - Decreased zinc in the development and progression of malignancy: an important
      common relationship and potential for prevention and treatment of carcinomas.
AB  - INTRODUCTION: Efficacious chemotherapy does not exist for treatment or prevention
      of prostate, liver, and pancreatic carcinomas, and some other cancers that
      exhibit decreased zinc in malignancy. Zinc treatment offers a potential solution;
      but its support has been deterred by adverse bias. Areas covered: 1. The clinical
      and experimental evidence for the common ZIP transporter/Zn down regulation in
      these cancers. 2. The evidence for a zinc approach to prevent and/or treat these
      carcinomas. 3. The issues that introduce bias against support for the zinc
      approach. Expert opinion: ZIP/Zn downregulation is a clinically established
      common event in prostate, hepatocellular and pancreatic cancers. 2. Compelling
      evidence supports the plausibility that a zinc treatment regimen will prevent
      development of malignancy and termination of progressing malignancy in these
      cancers; and likely other carcinomas that exhibit decreased zinc. 3.
      Scientifically-unfounded issues that oppose this ZIP/Zn relationship have
      introduced bias against support for research and funding of a zinc treatment
      approach. 4. The clinically-established and supporting experimental evidence
      provide the scientific credibility that should dictate the support for research
      and funding of a zinc approach for the treatment and possible prevention of these
      cancers. 5. This is in the best interest of the medical community and the public
      at-large.

PMID- 27885882
TI  - State of the art of ultrasound in the assessment of psoriasis and psoriatic
      arthritis.
AB  - INTRODUCTION: Ultrasound (US) is a rapidly evolving technique that is gaining
      increasing success in the assessment of psoriatic arthritis (PsA). Recently, new
      research avenues have been opened, and these are focused on the potential of US
      for the assessment of extra musculoskeletal areas such as skin and nails. This
      permits work on the concept of 'holistic US assessment of PsA'. Areas covered:
      Here, we analyze the potential role of US in the global assessment of PsA.
      Additionally, we provide the current evidence supporting its application in
      routine clinical practice. Literature was obtained from medical databases
      including PubMed and Embase. Expert commentary: US can detect not only structural
      abnormalities but also minimal blood flow changes at the superficial soft tissue
      level. This makes it a great tool for the global assessment of disease activity
      in PsA, in which persistently active disease plays a major role in causing
      anatomical damage and physical functional disability.

PMID- 27885881
TI  - Spectral analysis of hearing protector impulsive insertion loss.
AB  - OBJECTIVE: To characterise the performance of hearing protection devices (HPDs)
      in impulsive-noise conditions and to compare various protection metrics between
      impulsive and steady-state noise sources with different characteristics. DESIGN:
      HPDs were measured per the impulsive test methods of ANSI/ASA S12.42- 2010 .
      Protectors were measured with impulses generated by both an acoustic shock tube
      and an AR-15 rifle. The measured data were analysed for impulse peak insertion
      loss (IPIL) and impulsive spectral insertion loss (ISIL). These impulsive
      measurements were compared to insertion loss measured with steady-state noise and
      with real-ear attenuation at threshold (REAT). STUDY SAMPLE: Tested HPDs included
      a foam earplug, a level-dependent earplug and an electronic sound-restoration
      earmuff. RESULTS: IPIL for a given protector varied between measurements with the
      two impulse noise sources, but ISIL agreed between the two sources. The level
      dependent earplug demonstrated level-dependent effects both in IPIL and ISIL.
      Steady-state insertion loss and REAT measurements tended to provide a
      conservative estimate of the impulsively-measured attenuation. CONCLUSIONS:
      Measurements of IPIL depend strongly on the source used to measure them,
      especially for HPDs with less attenuation at low frequencies. ISIL provides an
      alternative measurement of impulse protection and appears to be a more complete
      description of an HPD's performance.

PMID- 27885883
TI  - College students' stigmatization of people with mental illness: familiarity,
      implicit person theory, and attribution.
AB  - BACKGROUND: Stigma associated with mental illness (MI) results in
      underutilization of mental health care. We must understand factors contributing
      to stigma to shape anti-stigma campaigns. AIMS: To investigate the factors
      influencing stigma in university students. METHOD: Undergraduate psychology
      students completed measures on causal attribution, stigma, social distance,
      implicit person theory (IPT), and familiarity. RESULTS: The hypothesis was
      partially supported; people who felt personality traits were unchangeable (i.e.
      entity IPT) were more likely to stigmatize individuals with mental disorders and
      desired more social distance from them. Familiarity with people with a MI
      individually predicted less desire for social distance, yet the redundancy of the
      predictors made the effect of familiarity on stigma fall just short of
      statistical significance. Judgments of biogenetic causal attribution were related
      to higher stigma levels, but not so when familiarity and IPT were taken into
      account. CONCLUSIONS: Educational campaigns may be effective by focusing on
      aspects of MI highlighting similarity with non-diagnosed people, and that people
      with MI can recover.

PMID- 27885884
TI  - About the advantages and disadvantages of discrete-event simulation for health
      economic analyses.

PMID- 27885885
TI  - Septic encephalopathy and septic encephalitis??.
AB  - INTRODUCTION: During the last two decades, septic encephalopathy (SE) was
      recognized as a clinically relevant problem with a high prevalence in patients at
      admission and during their hospital stay. SE is a condition associated with
      increased mortality and morbidity such as long-term cognitive impairment. Areas
      covered: This review illustrates the pathophysiology of sepsis-associated
      encephalopathy and encephalitis involving blood-brain-barrier dysfunction and
      neuroinflammation caused by endothelial and microglial activation by endogenous
      or pathogen-derived compounds, hypoxia by impaired microvascular regulation and
      septic shock as well as imbalance of neurotransmitters. The continuum between
      septic-embolic and septic-metastatic encephalitis and SE is underlined by
      histological findings. The options of technical examinations and biomarkers to
      diagnose SE are discussed together with established therapeutic options as well
      as current experimental approaches. Expert commentary: An outlook for clinicians
      is provided including promising diagnostic approaches by means of new imaging
      techniques. Clinical trials with drugs already established for other indications
      such as statins, erythropoietin and minocycline are warranted in the future.

PMID- 27885886
TI  - Atrial fibrillation in patients with chronic lymphocytic leukemia (CLL).
AB  - Although preliminary data suggests that ibrutinib may increase risk of atrial
      fibrillation (AF), the incidence of AF in a general cohort of chronic lymphocytic
      leukemia (CLL) patients is unknown. We evaluated the prevalence of AF at CLL
      diagnosis and incidence of AF during follow-up in 2444 patients with newly
      diagnosed CLL. A prior history of AF was present at CLL diagnosis in 148 (6.1%).
      Among the 2292 patients without history of AF, 139 (6.1%) developed incident AF
      during follow-up (incidence approximately 1%/year). Older age (p < .0001), male
      sex (p = .01), valvular heart disease (p = .001), and hypertension (p = .04) were
      associated with risk of incident AF on multivariate analysis. A predictive model
      for developing incident AF constructed from these factors stratified patients
      into 4 groups with 10-year rates of incident AF ranging from 4% to 33% (p <
      .0001). This information provides context for interpreting rates of AF in CLL
      patients treated with novel therapies.

PMID- 27885888
TI  - Cangrelor in combination with ticagrelor provides consistent and potent P2Y12
      inhibition during and after primary percutaneous coronary intervention in real
      world patients with ST-segment-elevation myocardial infarction.
AB  - Patients pretreated with ticagrelor with less than 1 hour from percutaneous
      coronary intervention (PCI) or receiving ticagrelor in cath lab were
      prospectively included and received cangrelor. Cangrelor was infused for 2 hours
      and platelet function was assessed as P2Y12 reactivity units (PRU) with the
      VerifyNow P2Y12 function assay before start of infusion, 15 min after the start
      of infusion, and 30 min after the end of infusion. A total of n = 32 patients
      with an average age of 68 (+/-13) years with n = 22 (69%) males were included.
      The level of P2Y12 inhibition before cangrelor infusion was started was 249 PRU
      (IQR 221-271). After 15 min of cangrelor infusion the P2Y12 reactivity was
      markedly decreased to 71 PRU (IQR 52-104, p < 0.001). At 30 min after end of
      infusion PRU remained within the therapeutic range, 89 PRU (IQR 50-178; p < 0.001
      for comparison with preinfusion) with only n = 4 (12.5%) patients with PRU >225.
      Results were consistent between patients receiving ticagrelor prehospital or in
      the cath lab and no statistical differences in PRU were noted between the two
      groups in any of the three measurements. In conclusion, cangrelor in combination
      with ticagrelor results in consistent and strong P2Y12 inhibition during and
      after infusion and cangrelor may bridge the gap until oral P2Y12 inhibitors
      achieve effect in real-world STEMI patients undergoing primary PCI.

PMID- 27885887
TI  - Cell therapies for Parkinson's disease: how far have we come?
AB  - Over the past three decades, significant progress has been made in the
      development of potential regenerative cell-based therapies for neurodegenerative
      disease, with most success being seen in Parkinson's disease. Cell-based
      therapies face many challenges including ethical considerations, potential for
      immune-mediated rejection with allogeneic and xenogeneic tissue, pathological
      spread of protein-related disease into the grafted tissue as well as the risk of
      graft overgrowth and tumorigenesis in stem cell-derived transplants. Preclinical
      trials have looked at many tissue types of which the most successful to date have
      been those using fetal ventral mesencephalon grafts, which led to clinical
      trials, which have shown that in some cases they can work very well. With
      important proof-of-concept derived from these studies, there is now much interest
      in how dopaminergic neurons derived from stem cell sources could be used to
      develop cell-based therapies suitable for clinical use, with clinical trials
      poised to enter the clinic in the next couple of years.

PMID- 27885889
TI  - The assessment of skin picking in adolescence: psychometric properties of the
      Skin Picking Scale-Revised (German version).
AB  - BACKGROUND: Skin picking disorder has received growing attention since the
      release of DSM-5, yet there are no evidence-based assessment instruments for
      adolescent samples. AIM: The present study examines the psychometric properties
      of the Skin Picking Scale-Revised (SPS-R, German version) in adolescents.
      METHODS: A total of 76 adolescents (96% female) completed the SPS-R, the Clinical
      Psychological Diagnostic System (KPD-38), and a questionnaire assessing
      demographics and clinical characteristics online. RESULTS: The SPS-R had high
      internal consistency (alpha = 0.89) and significant small-to-medium correlations
      with reduced competence skills, psychological impairment, general life
      satisfaction, social support, and social problems on the KPD-38. Similar to prior
      findings for adults, an exploratory factor analysis suggested a two-factor model
      for the SPS-R in adolescents. Group comparisons failed to show significant
      differences on SPS-R scores between participants with and without dermatological
      conditions. CONCLUSIONS: The current results suggest that the SPS-R can be useful
      in adolescent samples as a reliable and valid instrument for the assessment of
      skin picking severity. Future research investigating scale validity and factor
      structure in a clinical sample of adolescent skin pickers is warranted.

PMID- 27885890
TI  - Use of a thrombopoietin receptor agonist in von Willebrand disease type 2B
      (p.V1316M) with severe thrombocytopenia and intracranial hemorrhage.
AB  - We present here a 63-year old woman with a long history of immune
      thrombocytopenia. She was hospitalized for a traumatic intracranial hemorrhage
      with thrombocytopenia. Following inefficient treatment of four platelet
      transfusions, immunoglobulins, and corticosteroids, we initiated treatment with a
      thrombopoietin (TPO) receptor agonist (eltrombopag 25 mg/d) with a good efficacy.
      Her mother and sister also had chronic thrombocytopenia. Clinical history,
      hemostasis results, and gene analysis revealed von Willebrand disease (VWD) type
      2B with the mutation (c.3946G>A; p.V1316M), which combines a von Willebrand
      factor defect with severe thrombocytopenia, as well as a thrombocytopathy. The
      efficacy of TPO receptor agonists appears to counterbalance, at least to some
      extent, the thrombocytopathy associated with this mutation. As such, the use of
      TPO receptor agonists could represent an alternative therapeutic approach in
      cases of VWD type 2B with severe thrombocytopenia.

PMID- 27885891
TI  - Wiskott-Aldrich syndrome in a child presenting with macrothrombocytopenia.
AB  - Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease resulting
      from variants in the WAS gene, characterized by a triad of immunodeficiency,
      eczema, and thrombocytopenia. Despite the fact that WAS is traditionally
      differentiated from immune thrombocytopenia (ITP) by small size of WAS platelets,
      in practice, microthrombocytopenia may occasionally not be present, and in
      certain cases, WAS patients exhibit some parallelism to ITP patients. We
      characterized one patient presenting with the classic form of the disease but
      increased mean platelet volume. Molecular studies revealed a novel hemizygous 1
      bp deletion in WAS gene, c.802delC, leading to a frameshift and stop codon at
      amino acid 308 (p.Arg268Glyfs*40). Next-generation sequencing of a total of 70
      additional genes known to harbor variants implicated in inherited platelet
      disorders did not identify additional defects. The pathogenesis of
      macrothrombocytopenia in this case is not known, but probably the coexistence of
      a still unidentified additional genetic variant might be involved.

PMID- 27885892
TI  - Invited Commentary on "MR Enterography of Inflammatory Bowel Disease with
      Endoscopic Correlation".

PMID- 27885893
TI  - Tumor-Vessel Relationships in Pancreatic Ductal Adenocarcinoma at Multidetector
      CT: Different Classification Systems and Their Influence on Treatment Planning.
AB  - Treatment of pancreatic ductal adenocarcinoma (PDAC) remains a challenge, given
      its propensity for early systemic spread and growth into the adjacent vital
      vascular structures. With the advent of newer surgical techniques and
      chemoradiation therapies, multidetector computed tomography (CT) plays a crucial
      role in the identification of patients with borderline resectable disease who may
      benefit from such treatments. Stage III PDAC is divided into two categories
      locally advanced, defined by arterial encasement or nonreconstructible
      portovenous axis involvement; and borderline resectable, defined by limited
      arterial involvement and/or reconstructible portovenous involvement. A consensus
      definition for stage III borderline resectable PDAC has been proposed by the
      Americas Hepato-Pancreato-Biliary Association, the Society of Surgical Oncology,
      and the Society for Surgery of the Alimentary Tract and has gained widespread
      use. Evaluation of borderline resectable disease involves the identification of
      the circumferential and longitudinal relationship of the tumor with its
      neighboring vessels, markers of vascular invasion, and aberrant anatomic
      structures that alter the surgical approach. Furthermore, the use of template
      based radiology reporting may increase the objectivity of the evaluation and
      mandate the provision of all of the key descriptors required for a comprehensive
      evaluation of the disease. In this review, the staging of PDAC at multidetector
      CT is described, with reference to the evaluation of the tumor-vessel interface
      as it guides treatment planning, along with a discussion of the key descriptors
      of PDAC at multidetector CT and their importance. Examples are provided of the
      imaging findings of borderline resectable disease and different surgical
      approaches, along with a discussion on the importance of standardized terminology
      and template-based reporting. (c)RSNA, 2016.

PMID- 27885894
TI  - MR Enterography of Inflammatory Bowel Disease with Endoscopic Correlation.
AB  - Crohn disease (CD) and ulcerative colitis (UC) are the two main forms of
      idiopathic inflammatory bowel disease (IBD). CD is a transmural chronic
      inflammatory disorder that can affect any part of the gastrointestinal tract in a
      discontinuous distribution. UC is a mucosal and submucosal chronic inflammatory
      disease that typically originates in the rectum and may extend proximally in a
      continuous manner. In treating patients with CD and UC, clinicians rely heavily
      on accurate diagnoses and disease staging. Magnetic resonance (MR) enterography
      used in conjunction with endoscopy and histopathologic analysis can help
      accurately diagnose and manage disease in the majority of patients. Endoscopy is
      more sensitive for detection of the early-manifesting mucosal abnormalities seen
      with IBD and enables histopathologic sampling. MR enterography yields more
      insightful information about the pathologic changes seen deep to the mucosal
      layer of the gastrointestinal tract wall and to those portions of the small bowel
      that are not accessible endoscopically. CD can be classified into active
      inflammatory, fistulizing and perforating, fibrostenotic, and reparative and
      regenerative phases of disease. Although CD has a progressive course, there is no
      stepwise progression between these disease phases, and various phases may exist
      at the same time. The endoscopic and MR enterographic features of UC can be
      broadly divided into two categories: acute phase and subacute-chronic phase.
      Understanding the endoscopic features of IBD and the pathologic processes that
      cause the MR enterographic findings of IBD can help improve the accuracy of
      disease characterization and thus optimize the medication and surgical therapies
      for these patients. (c)RSNA, 2016.

PMID- 27885895
TI  - Validity and reliability of the Very Short form of the Physical Self-Inventory
      among Turkish adolescents.
AB  - The study aimed to test the validity and reliability of the Very Short form of
      the Physical Self-Inventory (PSI-VS) among a sample of 635 Turkish adolescents.
      These adolescents have completed the 12 original items of the PSI-VS, plus a
      positively worded reformulation of the single reverse-keyed item of the physical
      attractiveness subscale. A series of confirmatory factor analyses was used to
      examine the psychometric properties of the original and modified versions of the
      PSI-VS. Findings revealed superior psychometric properties with the modified
      version than with the original set of items. The modified version was thus
      subsequently used to examine its factor structure invariance across sexes, age
      groups and sport practice involvement. Results not only report that this version
      was fully invariant across, but also that latent means were significantly
      different across sexes and sport practice involvement. In sum, the Turkish
      modified version of the PSI-VS presents acceptable psychometric properties and
      may be used to repeatedly and/or intensively assess participants' physical self
      perceptions in the context of sport and exercise interventions.

PMID- 27885896
TI  - Dual nanoparticle drug delivery: the future of anticancer therapies?

PMID- 27885897
TI  - False feedback and beliefs influence name recall in younger and older adults.
AB  - Feedback is an important self-regulatory process that affects task effort and
      subsequent performance. Benefits of positive feedback for list recall have been
      explored in research on goals and feedback, but the effect of negative feedback
      on memory has rarely been studied. The current research extends knowledge of
      memory and feedback effects by investigating face-name association memory and by
      examining the potential mediation of feedback effects, in younger and older
      adults, through self-evaluative beliefs. Beliefs were assessed before and after
      name recognition and name recall testing. Repeated presentation of false positive
      feedback was compared to false negative feedback and a no feedback condition.
      Results showed that memory self-efficacy declined over time for participants in
      the negative and no feedback conditions but was sustained for those receiving
      positive feedback. Furthermore, participants who received negative feedback felt
      older after testing than before testing. For name recall, the positive feedback
      group outperformed the negative feedback and no feedback groups combined, with no
      age interactions. The observed feedback-related effects on memory were fully
      mediated by changes in memory self-efficacy. These findings advance our
      understanding of how beliefs are related to feedback in memory and inform future
      studies examining the importance of self-regulation in memory.

PMID- 27885898
TI  - iPSC in the past decade: the Japanese dominance.

PMID- 27885899
TI  - Regenerative Medicine: lessons from Mother Nature.
AB  - Regenerative medicine strategies for the restoration of functional tissue have
      evolved from the concept of ex vivo creation of engineered tissue toward the
      broader concept of in vivo induction of functional tissue reconstruction.
      Multidisciplinary approaches are being investigated to achieve this goal using
      evolutionarily conserved principles of stem cell biology, developmental biology
      and immunology, current methods of engineering and medicine. This evolution from
      ex vivo tissue engineering to the manipulation of fundamental in vivo tenets of
      development and regeneration has the potential to capitalize upon the incredibly
      complex and only partially understood ability of cells to adapt, proliferate,
      self-organize and differentiate into functional tissue.

PMID- 27885900
TI  - Recreating composition, structure, functionalities of tissues at nanoscale for
      regenerative medicine.
AB  - Nanotechnology offers significant potential in regenerative medicine,
      specifically with the ability to mimic tissue architecture at the nanoscale. In
      this perspective, we highlight key achievements in the nanotechnology field for
      successfully mimicking the composition and structure of different tissues, and
      the development of bio-inspired nanotechnologies and functional nanomaterials to
      improve tissue regeneration. Numerous nanomaterials fabricated by
      electrospinning, nanolithography and self-assembly have been successfully applied
      to regenerate bone, cartilage, muscle, blood vessel, heart and bladder tissue. We
      also discuss nanotechnology-based regenerative medicine products in the clinic
      for tissue engineering applications, although so far most of them are focused on
      bone implants and fillers. We believe that recent advances in nanotechnologies
      will enable new applications for tissue regeneration in the near future.

PMID- 27885902
TI  - Regenerative medicine: looking backward 10 years further on.
AB  - The last decade has seen considerable changes in the Regenerative Medicine
      industry, but unfortunately the hope for numerous treatments that 'replace or
      regenerate human cells, tissues or organs to restore or establish normal
      function' has not yet emerged. In contrast to this, there have been major
      advances in the field of cellular immunotherapy though some do not consider these
      to be Regenerative Medicines. Regulatory changes have in some cases improved the
      route to a marketing license but they have not been matched by clarification of
      the complex, national reimbursement processes for cell-based treatments and this
      has adversely affected a number of leading Regenerative Medicine Companies. The
      review considers the direction that the industry may go in the future in relation
      to scientific, manufacturing and clinical strategies which may improve the rate
      of success of new therapies..

PMID- 27885901
TI  - The bone marrow pericyte: an orchestrator of vascular niche.
AB  - The concept of pericyte has been changing over years. This cell type was believed
      to possess only a function of trophic support to endothelial cells and to
      maintain vasculature stabilization. In the last years, the discovery of
      multipotent ability of perivascular populations led to the concept of vessel/wall
      niche. Likewise, several perivascular populations have been identified in animal
      and human bone marrow. In this review, we provide an overview on bone marrow
      perivascular population, their cross-talk with other niche components,
      relationship with bone marrow stromal stem cells, and similarities and
      differences with the perivascular population of the vessel/wall niche. Finally,
      we focus on the regenerative potential of these cells and the forthcoming
      challenges related to their use as cell therapy products.

PMID- 27885903
TI  - Opinions of nephrologists on the efficacy and tolerance of statins in
      hemodialysis patients.
AB  - Large randomized controlled trials have not confirmed the effects of statin
      therapy on reduction of cardiovascular morbidity and mortality in end-stage
      kidney disease, despite that statins are still widely prescribed by nephrologists
      to chronic dialysis patients. The aim of the study was to analyze the attitudes
      of nephrologists towards statin use in hemodialysis patients. Self-designed
      questionnaire, containing 18 questions, was distributed among 115 nephrologists.
      The survey contained description of the results of 3 largest statin trials in
      nephrology. The questions referred to the interpretation of trial results and the
      safety and efficacy of statin therapy and dose adjustments required in dialysis
      patients. 83% among 72 nephrologists who returned the questionnaire prescribed
      statins to their dialysis patients for secondary prevention of cardiovascular
      events. 90% prescribed atorvastatin. 64% nephrologists did not modify statin dose
      at the start of hemodialysis treatment and 47% before elective surgery. Liver
      disease was indicated as a main reason for dose modification in hemodialysis
      patients. Statin-induced myopathy was observed by 65% nephrologists and 61%
      reported a case of increased liver enzymes. 51% of nephrologists did not
      routinely discuss the possible benefits and risks of statin therapy with their
      patients. Statins are still widely prescribed and considered safe and effective
      lipid-lowering therapy in dialysis patients by most nephrologists.

PMID- 27885904
TI  - The effect of P2Y12 inhibition on platelet activation assessed with aggregation-
      and flow cytometry-based assays.
AB  - Patients on P2Y12 inhibitors may still develop thrombosis or bleeding
      complications. Tailored antiplatelet therapy, based on platelet reactivity
      testing, might reduce these complications. Several tests have been used, but
      failed to show a benefit of tailored antiplatelet therapy. This could be due to
      the narrowness of current platelet reactivity tests, which are limited to
      analysis of platelet aggregation after stimulation of the adenosine diphosphate
      (ADP)-pathway. However, the response to ADP does not necessarily reflect the
      effect of P2Y12 inhibition on platelet function in vivo. Therefore, we
      investigated whether measuring platelet reactivity toward other physiologically
      relevant agonists could provide more insight in the efficacy of P2Y12 inhibitors.
      The effect of in vitro and in vivo P2Y12 inhibition on alphaIIbbeta3-activation,
      P-selectin and CD63-expression, aggregate formation, release of alpha, and dense
      granules content was assessed after stimulation of different platelet activation
      pathways. Platelet reactivity measured with flow cytometry in 72 patients on
      P2Y12 inhibitors was compared to VerifyNow results. P2Y12 inhibitors caused
      strongly attenuated platelet fibrinogen binding after stimulation with peptide
      agonists for protease activated receptor (PAR)-1 and -4, or glycoprotein VI
      ligand crosslinked collagen-related peptide (CRP-xl), while aggregation was
      normal at high agonist concentration. P2Y12 inhibitors decreased PAR-agonist and
      CRP-induced dense granule secretion, but not alpha granule secretion. A
      proportion of P2Y12-inhibitor responsive patients according to VerifyNow,
      displayed normal fibrinogen binding assessed with flow cytometry after
      stimulation with PAR-agonists or CRP despite full inhibition of the response to
      ADP, indicating suboptimal platelet inhibition. Concluding, measurement of
      platelet fibrinogen binding with flow cytometry after stimulation of thrombin- or
      collagen receptors in addition to ADP response identifies different patients as
      nonresponders to P2Y12 inhibitors, compared to only ADP-induced aggregation-based
      assays. Future studies should investigate the value of both assays for monitoring
      on-treatment platelet reactivity.

PMID- 27885906
TI  - Supporting women with toileting in palliative care: use of the female urinal for
      bladder management.
AB  - AIMS AND OBJECTIVES: This study explored whether a female urinal is an
      acceptable, safe and effective product to meet the toileting requirements of
      women receiving palliative care on oncology wards in hospitals. BACKGROUND: There
      is minimal evidence on how urinary incontinence should be managed in women
      receiving palliative care. Female urinals may present an option. There have been
      two general reviews of products, but no formal evaluation since 1999. METHODS:
      This qualitative interview study used semi-structured interviews. Eleven healthy
      volunteers, 9 patients and 7 staff members used (or assisted with) a VernaFem
      (Vernacare) female urinal and were subsequently interviewed. Directed content
      analysis was used to analyse the interviews. RESULTS: User testing confirmed that
      the VernaFem is an acceptable, safe and effective product. Design improvements
      were suggested. CONCLUSIONS: While unlikely to be suitable for all patients,
      hospitals should consider offering a female urinal to patients in receipt of
      palliative care.

PMID- 27885905
TI  - Facilitating terminal discharge: fulfilling the hospitalised patient's wish for
      home death in the final hours.
AB  - BACKGROUND: Terminal discharge (TD) is the rapid discharge of a hospitalised
      patient when death is imminent. Its time-limited nature makes it challenging,
      particularly for ward nurses. AIM: To report the development of a structured TD
      framework, and determine if the framework can expedite TD processes and improve
      nurses' experience in conducting TDs. METHODS: A 3-phase audit was carried out in
      a Singapore hospital. The baseline and post intervention audits evaluated the
      time taken for TD, incidence of prescription errors, continuity of care, and
      timeliness of equipment arrangement. Nurse satisfaction was assessed through a
      written survey. Interventions encompassed the implementation of workflow changes
      and a TD guide. RESULTS: The mean time taken to complete TDs was shorter in the
      post-compared to pre-intervention phase (2.9+/-1.4 vs. 4.6+/-2.3 hours
      respectively, p<0.01). Approximately 89% of nurses who used the TD guide were
      satisfied that it made TDs easier. CONCLUSION: A structured TD framework is
      effective in expediting TDs and improving nurse satisfaction.

PMID- 27885907
TI  - The challenges of implementing a multi-centre audit of end-of-life care in care
      homes.
AB  - AIMS: This article aims to share the experience of a hospice in facilitating a
      multi-centre audit of end-of-life care in care homes, particularly noting the
      challenges and enablers of carrying out the audit. METHODS: The audit was a
      retrospective multi-centre survey of bereaved relatives/next of kin of residents
      who died in the care home, using an anonymous, validated questionnaire: the
      Family Perception of Care Scale. Questionnaires were sent 3-months after
      bereavement. Returned questionnaires were analysed using SPSS and Excel. The care
      homes were in areas encompassing outer and inner city populations. FINDINGS: The
      team identified eight challenges to the audit process, in particular, embedding
      procedures within the care homes, non-responses and developing action plans for
      improvement. CONCLUSION: Overall, the audit provided an indication of where
      improvements could be made and where care was already excellent, built confidence
      and increased expertise in the care-home staff.

PMID- 27885908
TI  - Moving on from patient labelling in palliative care.

PMID- 27885909
TI  - Research roundup.
AB  - Synopses of a selection of recently published research articles of relevance to
      palliative care.

PMID- 27885911
TI  - End-of-life prognostic indicators in patients with COPD: part 2.
AB  - In the UK, chronic respiratory diseases cause 13% of adult disability. The major
      chronic respiratory disease is chronic obstructive pulmonary disease (COPD), a
      condition involving chronic airway inflammation that causes airflow obstruction
      and destruction of lung tissue. This leads to a progressive loss of respiratory
      membrane, which accounts for the clinical manifestation of COPD, which is
      difficulty maintaining sufficient gas exchange to meet metabolic demands. The
      primary cause is smoking, with the vast majority of COPD patients having a past
      or present history of smoking. However, exposure to industrial pollutants is also
      a contributing factor, as is a rare genetic predisposition to developing COPD.

PMID- 27885910
TI  - An end-of-life care nurse service for people with COPD and heart failure:
      stakeholders' experiences.
AB  - BACKGROUND: End-of-life care (EOLC) has historically been associated with cancer
      care. However, demographic changes indicate that future provision must also cater
      for other long term conditions (LTC). An EOLC-LTC service, delivered by
      palliative care nurses, is currently being piloted in one area in the East
      Midlands with patients with cardiac and respiratory disease. In order to inform
      future commissioning, it is important to gain the views and experiences of those
      involved with the service. AIMS: This study aimed to explore patients, and their
      partners, views and experiences of the EOLC-LTC service. METHODS: Semi-structured
      interviews were used as part of a case study design, involving six cases. Each
      case consisted of the patient, their nominated family member/carer and key
      healthcare professionals involved in their care as identified by the patient.
      This paper reports on the findings from the interviews conducted with the six
      patients and their family member/carers. Data were analysed thematically.
      RESULTS: From the interviews, the following themes were identified: experiences
      managing a long term cardio-respiratory condition, the nurse service, building a
      close/therapeutic relationship and fragmentation and integration. CONCLUSIONS:
      This study has shown that the EOLC-LTC service is welcomed and highly regarded by
      patients and their family members/carers. Further studies are required to explore
      the views and experiences of other key stakeholders and to evaluate how well the
      pilot operates within the wider care pathway.

PMID- 27885912
TI  - Politics and palliative care: Mauritania.
AB  - Dion Smyth's review of palliative nursing on the internet.

PMID- 27885913
TI  - Platelet index levels and cardiovascular mortality in incident peritoneal
      dialysis patients: a cohort study.
AB  - Prior studies have shown that the levels of some platelet (PLT) indices were
      associated with mortality in patients undergoing hemodialysis. We aimed to
      investigate whether the changes in PLT indices associated with mortality in
      patients on peritoneal dialysis (PD). A single-center, retrospective
      observational cohort study was conducted in incident PD patients from 1 January
      2006 to 31 December 2012, and followed up until 31 December 2014. Cox
      proportional hazard models were used to examine the relationships between the
      levels of PLT indices including PLT, plateletcrit (PCT), mean platelet volume
      (MPV), platelet distribution width (PDW), platelet large cell ratio (PLCR), and
      mortality. Of 1324 patients, 276 (20.8%) died during follow-up (median, 37; IQR,
      3-107.4 months), among which 134 were due to cardiovascular diseases (CVD). The
      highest tertile of PLT levels at baseline was associated with increased risk for
      cardiovascular mortality after adjustment for demographic, clinical
      characteristics, and laboratory variables (hazard ratio [HR]:1.93; 95% confidence
      interval [CI]: 1.16-3.20). The similar treads were also observed in the middle
      and the highest tertile of the PCT level (HR: 1.68, 95%CI: 1.00-2.81 and HR:
      1.89, 95%CI: 1.14-3.14, respectively). In addition, the highest tertile of PCT
      was associated with increased all-cause mortality (HR: 1.41, 95%CI: 1.01-1.96).
      However, none of the associations in MPV, PDW, and PLCR analyses reached
      statistical significance (HR: 0.71, 95%CI: 0.43-1.16; HR: 0.72, 95%CI: 0.45-1.18
      and HR: 0.74, 95%CI: 0.46-1.19, respectively). These results suggest that higher
      PLT and PCT may be associated with higher risk for cardiovascular mortality in
      incident PD patients. Additional studies are needed to investigate whether
      correction of these two PLT indices reduces the risk.

PMID- 27885914
TI  - Chronic pain in older adults: prevalence, incidence, and risk factors.
AB  - OBJECTIVES: Chronic pain is common in older adults, yet little is known of its
      development and the factors that predict its persistence and onset at old age.
      The aims of this longitudinal cohort study were to examine the prevalence and
      incidence of chronic pain and to explore possible risk factors for its
      persistence and onset in a representative sample of older Swedish adults. METHOD:
      Data were collected through questionnaires and followed up after 12 and 24
      months. Chronic pain was defined as pain symptoms that lasted more than 3 months,
      regardless of the specific cause or site. Logistic regression analyses were used
      to identify odds ratios (ORs) with 95% confidence intervals (CIs) for potential
      predictors. RESULTS: Out of 2000 older adults approached (aged 65-103 years),
      1141 were included in the study. Chronic pain was reported among 38.5% of the
      participants, and was more common among females and among adults over 85 years of
      age. The incidence was estimated to be 5.4% annually. Being female (OR 3.19, 95%
      CI 1.04-9.59), having a lower body mass index (BMI; OR 0.89, 95% CI 0.79-0.99),
      more than one pain location (OR 4.02, 95% CI 1.56-10.35), higher severity (OR
      1.79, 95% CI 1.13-2.83), and longer duration (OR 1.08, 95% CI 1.01-1.15) were
      associated with the persistence of chronic pain, but this association did not
      remain significant for men when divided by gender. Younger age (OR 0.89, 95% CI
      0.89-0.99) was associated with new onset of chronic pain. CONCLUSIONS: Even
      though pain was often highly prevalent and persistent, our results show that both
      recovery and onset of pain occurred. Pain characteristics, rather than age
      related symptoms and psychosocial variables, predicted pain persistence among
      older women but not among older men. These findings highlight the importance of
      early pain management in the prevention of future pain.

PMID- 27885915
TI  - Effect of an SNP in SCAP gene on lipid-lowering response to rosuvastatin in
      Indian patients with metabolic syndrome.
AB  - AIM: Statins treat dyslipidemia associated with metabolic syndrome. Genetic
      factors contribute to variable response. Sterol regulatory element-binding
      factors cleavage-activating protein (SCAP) pathway regulates lipid homeostasis,
      so effect of SNP in SCAP gene on rosuvastatin response was studied. MATERIALS &
      METHODS: Metabolic syndrome patients with low-density lipoprotein-cholesterol
      >=130 mg/dl, were prescribed rosuvastatin 5 mg for 3 months. Lipids were measured
      initially and finally, and genotyping done. RESULTS & CONCLUSION: Sixty-three
      patients completed the study. Twenty-three were homozygous for AA while 40 were
      heterozygous. Significant association was found between post-treatment lipid
      values and SCAP genotypes but not with baseline values. Cholesterol (p = 0.002)
      and low-density lipoprotein-cholesterol (p = 0.008) were significantly reduced in
      patients carrying G allele as compared with AA. There was a significant effect of
      G allele on cholesterol reduction (p = 0.043). Out of total responders (achieving
      >23.58% total cholesterol reduction), 80.5% were 2386G carriers (GG+GA) and only
      19.5% were homozygous for A allele (p = 0.0048). SCAP 2386A>G gene polymorphism
      is a significant predictor of hypolipidemic response.

PMID- 27885918
TI  - Increased deficits in emotion recognition and regulation in children and
      adolescents with exogenous obesity.
AB  - OBJECTIVES: In this study we aimed to evaluate emotion recognition and emotion
      regulation skills of children with exogenous obesity between the ages of 11 and
      18 years and compare them with healthy controls. METHODS: The Schedule for
      Affective Disorders and Schizophrenia for School Aged Children was used for
      psychiatric evaluations. Emotion recognition skills were evaluated using Faces
      Test and Reading the Mind in the Eyes Test. The Difficulties in Emotions
      Regulation Scale was used for evaluating skills of emotion regulation. RESULTS:
      Children with obesity had lower scores on Faces Test and Reading the Mind in the
      Eyes Test, and experienced greater difficulty in emotional regulation skills.
      CONCLUSIONS: Improved understanding of emotional recognition and emotion
      regulation in young people with obesity may improve their social adaptation and
      help in the treatment of their disorder. To the best of our knowledge, this is
      the first study to evaluate both emotional recognition and emotion regulation
      functions in obese children and obese adolescents between 11 and 18 years of age.

PMID- 27885916
TI  - ATIC missense variant affects response to methotrexate treatment in rheumatoid
      arthritis patients.
AB  - AIM: The study was aimed at investigation of several gene variants of folate
      pathway enzymes for their potential association with methotrexate (MTX) treatment
      response in patients with rheumatoid arthritis. PATIENTS & METHODS: Four hundred
      and twenty two Caucasian patients were classified as good or poor responders, and
      subsequently genotyped for common SNPs in DHFR, FPGS and ATIC genes. RESULTS: No
      significant differences were observed in case of DHFR and FGPS SNPs. As for ATIC
      rs2372536 (Thr116Ser), GG minor genotype was significantly associated with good
      response to MTX (OR: 2.40; 95% CI: 1.30-4.42; p = 0.005), which was confirmed by
      multivariate analysis. CONCLUSION: The results of the study suggest that ATIC
      missense rs2372536 SNP may influence response to MTX therapy in rheumatoid
      arthritis patients.

PMID- 27885920
TI  - E-health in low to middle income countries.

PMID- 27885924
TI  - Editorial.

PMID- 27885925
TI  - Group detection of DON and its modified forms by an ELISA kit.
AB  - Deoxynivalenol (DON) and its modified forms (3-, and 15-acetyl-DON, DON-3
      glucoside) are commonly analysed by chromatographic methods. Indeed, coupled with
      proper extraction and clean-up, LC-MS represents the best approach for multi
      mycotoxin measurements. On the other hand, immunochemistry-based methods are
      possibly able to detect a family of structurally related compounds, although the
      determination of single contributions is not possible so far. However, ELISA
      methods often lead to an apparent overestimation of the mycotoxins content
      because modified forms and matrix components can potentially cross-react with the
      antibodies (designed for the parent toxin). Several data about the possible cross
      reactivity of commercial DON-detecting ELISA kit are reported in the literature
      so far. Data are commonly obtained in buffer solutions or in matrix-matched
      solutions, but comparison of a set of naturally incurred samples has never been
      reported. In the present work the accuracy of a commercial DON-detecting ELISA
      kit was evaluated on naturally incurred soft wheat (n = 15) and maize (n = 15),
      taking into account the matrix effect. Recovery was calculated considering the
      DON concentration found by LC-MS/MS and the total DON concentration, expressed as
      the sum of DON and its modified forms found by LC-MS/MS. The obtained data
      clearly show that, when 3-modified forms of DON occur in the sample, the ELISA
      kit does actually detect them, thus returning an apparent overestimation if only
      DON content is considered. When the ELISA recovery is calculated on the total DON
      content, the accuracy of the analysis increases and the variability decreases.
      According to our data, the ELISA kit seems to be a promising group detection tool
      for the accurate evaluation of DON and its modified forms, expressed as sum of
      DON, DON-3Glc and 3Ac-DON, for soft wheat and maize samples.

PMID- 27885927
TI  - The quest for industrial enzymes from microorganisms.
AB  - Satoshi Omura, Professor Emeritus at Kitasato University, was awarded the Nobel
      Prize for his discovery of a substance of tremendous value to mankind from a
      microorganism. As a researcher who regularly deals with enzymes produced by
      microorganisms and a person engaged in microorganism-based business, Professor
      Omura's Nobel Prize fills me with great pride and joy. It is perhaps not
      surprising that this Nobel Prize-winning research would emerge from Asia,
      specifically Japan, where people live in harmony with nature rather than try to
      conquer it. At Amano Enzyme Inc., we devote ourselves to searching for novel
      enzymes from microorganisms. While incorporating my own experiences, I will
      recount the stories of a few discoveries of valuable enzyme-producing microbes in
      soil and bacterial strain libraries. I will also briefly introduce microbial
      strain library construction as a tool for facilitating the identification of the
      desired producing bacteria.

PMID- 27885926
TI  - Short polyhistidine peptides penetrate effectively into Nicotiana tabacum
      cultured cells and Saccharomyces cerevisiae cells.
AB  - The polyhistidine peptides (PHPs) have been previously reported as novel cell
      penetrating peptides and are efficiently internalized into mammal cells; however,
      penetration of PHPs into other cell types is unknown. In this study, the cellular
      uptake of PHPs in plant and yeast cells was found to be dependent on the number
      of histidines, and short PHPs (H6-H10 peptides) showed effective internalization.
      The H8 peptide showed the highest cell-penetrating capacity and localized to
      vacuoles in plant and yeast cells. Low-temperature conditions inhibited
      significantly the cellular uptake of short PHPs by both cells. However, net
      charge neutralization of PHPs also completely inhibited cellular uptake by plant
      cells, but not by yeast cells. These results indicate that short PHPs penetrate
      effectively into plant and yeast cells by similar mechanism with the exception of
      net charge dependency. The findings show the short PHPs are promising candidates
      for new delivery tools into plant and yeast cells.

PMID- 27885928
TI  - Epoch-making milestones in antibiotic exploratory researches in Japan.
AB  - Professor Satoshi Omura was awarded the 2015 Nobel Prize in Physiology or
      Medicine. He is the third to win the award for research on antibiotic, following
      Fleming' (UK, 1945, discovery of penicillin) and Waksman (USA, 1952, discovery of
      streptomycin), and the second person after Waksman to receive the award for
      research on actinomycetes. By focusing his research on macrolides stemming from
      leucomycin research rather than beta-lactams like penicillin or aminoglycosides
      like streptomycin, Prof. Omura realized many scientific achievements. These
      efforts finally led to the discovery of avermectin and its semi-synthetic
      derivative, ivermectin, considered a monumental contribution to the human race.
      In this manuscript, I will outline the chronicles of the epoch-making antibiotic
      exploratory researches preceding Prof. Omura.

PMID- 27885929
TI  - Pursuing the unlimited potential of microorganisms-progress and prospect of a
      fermentation company.
AB  - Production of pharmaceuticals and chemicals using microbial functions has
      bestowed numerous benefits onto society. The Nobel Prize awarded to Professor
      Omura, Distinguished Emeritus Professor of Kitasato University, showed the world
      the importance of the discovery and practical application of microorganisms. Now,
      increasing attention is turned toward the future path of this field. As people
      involved in the microorganism industry, we will review the industrial activities
      thus far and consider the possible future developments in this field and its
      potential contribution to society.

PMID- 27885930
TI  - Continuing fascination of exploration in natural substances from microorganisms.
AB  - In the search for novel organic compounds, I think it is of paramount importance
      not to overlook the pursuit of microorganism diversity and the abilities those
      microorganisms hold as a resource. In commemoration of Professor Satoshi Omura's
      Nobel Prize in Physiology or Medicine, I will briefly describe the microorganism
      that produces avermectin and then discuss how innovating isolation methods and
      pioneering isolation sources have opened the door to numerous new microorganism
      resources. Furthermore, as exploratory research of substances views the world
      from many different angles-from biological activity to a compound's
      physiochemical properties-it is possible to discover a novel compound from a well
      known microorganism. Based on this, I will discuss the future prospects of
      exploratory research.

PMID- 27885931
TI  - Development of new antituberculosis drugs from natural products.

PMID- 27885932
TI  - Natural products discovery from micro-organisms in the post-genome era.
AB  - With the decision to award the Nobel Prize in Physiology or Medicine to Drs. S.
      Omura, W.C. Campbell, and Y. Tu, the importance and usefulness of natural drug
      discovery and development have been revalidated. Since the end of the twentieth
      century, many genome analyses of organisms have been conducted, and accordingly,
      numerous microbial genomes have been decoded. In particular, genomic studies of
      actinomycetes, micro-organisms that readily produce natural products, led to the
      discovery of biosynthetic gene clusters responsible for producing natural
      products. New explorations for natural products through a comprehensive approach
      combining genomic information with conventional methods show great promise for
      the discovery of new natural products and even systematic generation of
      unnaturally occurring compounds.

PMID- 27885933
TI  - Sufficient intake of high amylose cornstarch maintains high colonic hydrogen
      production for 24 h in rats.
AB  - Colonic hydrogen (H2) can suppress oxidative stress and damage in the body. We
      examined the minimum requirement of high amylose cornstarch (HAS) to maintain
      high colonic H2 production for 24 h. Ileorectostomized and sham-operated rats
      were fed a control diet supplemented with or without 20% HAS for 7 days. Colonic
      starch utilization was determined. Next, rats were fed the control diet with or
      without 10% or 20% HAS for 14 or 28 days, respectively. Breath and flatus H2
      excretion for 24 h was measured. 1.04 g of resistant fraction in HAS was utilized
      for 24 h by colonic bacteria. High H2 excretion was not maintained for 24 h in
      rats fed the 10% HAS diet, from which only 0.89 g of resistant starch was
      estimated to be delivered. High colonic H2 production for 24 h would be
      maintained by delivering more HAS to the large intestine than is utilized.

PMID- 27885935
TI  - Anecdote of the Omura laboratory and the discovery of avermectin.
AB  - I first met Professor Omura, Distinguished Emeritus Professor, at The Kitasato
      Institute (Kitaken) when I was 28 years old. Since then, he has been my
      respectful supervisor as well as mentor. Looking back on those memories, I am
      deeply honored to write about the discovery and development of avermectin.

PMID- 27885934
TI  - The path to producing pharmaceuticals from natural products uncovered by academia
      from the perspective of a science coordinator.
AB  - To actualize the invention of all-Japanese medicines, the Department of
      Innovative Drug Discovery and Development (iD3) in the Japan Agency for Medical
      Research and Development (AMED) serves as the headquarters for the Drug Discovery
      Support Network. iD3 assists with creating research strategies for the seeds of
      medicines discovered by academia and provides technological support, intellectual
      property management, and aid for applying the seeds through industry-led efforts.
      In this review, from the perspective of a science coordinator, I will describe
      the current activities of the drug discovery support network and iD3 as well as
      the challenges and future developments of pharmaceutical research and development
      using the natural product drug discovery method.

PMID- 27885936
TI  - Celebrating Dr. Satoshi Omura, the recipient of the 2015 Nobel Prize in
      Physiology or Medicine.

PMID- 27885937
TI  - Phenotypic screening meets natural products in drug discovery.
AB  - The Nobel Prize in Physiology or Medicine 2015 was awarded for discoveries
      related to the control of parasitic diseases using natural products of microbial
      and plant origin. In current drug discovery programs, synthesized compounds are
      widely used as a screening source; however, this award reminds us of the
      importance of natural products. Here, we introduce our phenotypic screening
      methods based on changes in cell morphology and discuss their effectiveness and
      impact for natural products in drug discovery.

PMID- 27885939
TI  - Microbial innovations in the world of food.
AB  - Technological developments in Japan based on the results of microbial research
      were a major pillar supporting the postwar industrial revolution. The wellspring
      of these advancements was the sophisticated technology used in traditional
      brewing, a foundation of the characteristic Japanese food culture. In this
      manuscript, we will describe the fermentative production of amino acids and
      nucleic acids following the discovery of the umami component so distinct in
      Japanese cuisine, which finally revealed the true power of microbial production.
      Thereafter, we will describe acetic acid production stemming from brewed vinegar
      production and the fermentative production of some other organic acids. Finally,
      we will delve into the massive scale of innovations achieved by the discovery of
      valuable micro-organisms and how they have affected the field of food.

PMID- 27885938
TI  - Genomic analysis of Bacillus subtilis lytic bacteriophage phiNIT1 capable of
      obstructing natto fermentation carrying genes for the capsule-lytic soluble
      enzymes poly-gamma-glutamate hydrolase and levanase.
AB  - Bacillus subtilis strains including the fermented soybean (natto) starter produce
      capsular polymers consisting of poly-gamma-glutamate and levan. Capsular polymers
      may protect the cells from phage infection. However, bacteriophage phiNIT1
      carries a gamma-PGA hydrolase gene (pghP) that help it to counteract the host
      cell's protection strategy. phiNIT had a linear double stranded DNA genome of
      155,631-bp with a terminal redundancy of 5,103-bp, containing a gene encoding an
      active levan hydrolase. These capsule-lytic enzyme genes were located in the
      possible foreign gene cluster regions between central core and terminal redundant
      regions, and were expressed at the late phase of the phage lytic cycle. All
      tested natto origin Spounavirinae phages carried both genes for capsule degrading
      enzymes similar to phiNIT1. A comparative genomic analysis revealed the diversity
      among phiNIT1 and Bacillus phages carrying pghP-like and levan-hydrolase genes,
      and provides novel understanding on the acquisition mechanism of these enzymatic
      genes.

PMID- 27885940
TI  - Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2
      cells against ethanol-induced oxidative stress.
AB  - Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against
      ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the
      isolates, furofuran lignans 4-6, significantly protected rat hepatocytes against
      ethanol-induced oxidative stress by reducing intracellular reactive oxygen
      species levels, preserving antioxidative defense enzyme activities, and
      maintaining the glutathione content. Moreover, 4 dose-dependently induced the
      heme oxygenase-1 expression in HepG2 cells.

PMID- 27885941
TI  - GSTT1 (rs4025935) null genotype is associated with increased risk of sickle cell
      disease in the populations of Tabuk-Northwestern region of Saudi Arabia.
AB  - BACKGROUND: Glutathione system plays an important role in the protection of cells
      and tissue against damage from oxidative stress. Impairment of the glutathione
      system due to genetic polymorphism of GST genes may increase the risk and
      severity of sickle cell disease (SCD). Present study was, therefore, undertaken
      to examine the relative impact of the genetic polymorphism of GSTT1 and GSTM1
      (rs4025935 and rs71748309) on susceptibility and hematological aspects of the
      patients with SCD. METHODS: Present study included 100 patients with SCD and 200
      healthy controls from northwestern region of Saudi Arabia. GSTM1 and GSTT1
      (rs4025935 and rs71748309) genotypes were investigated by using single-tube
      multiplex PCR technique. RESULTS: It was observed that patients with SCD
      possessed significantly higher frequency of GSTT1 null genotype (26%) than
      healthy controls (15%), (P = 0.00001). Compared to the presence of GSTT1
      genotype, the OR for the GSTT1 null genotype were estimated to be 4.3 (2.17-8.64,
      P = 0.00001). However, such association was not observed with respect to the
      presence of GSTM1 null genotype. In addition, it was observed that SCD in
      patients with GSTT1 genotype, the mean percentage levels for HbF and HbS were
      0.48 and 35.4%, respectively; however, among SCD patients with GSTT1 null
      genotype, the mean percentage levels were significantly higher 1.62% (P = 0.004)
      and 39.38% (P = 0.02), respectively. CONCLUSION: GSTT1 null genotype is
      significantly associated with increased risk of SCD among the population of
      northwestern region of Saudi Arabia. In addition, it may be one of the important
      factors responsible for hematological manifestations of SCD.

PMID- 27885942
TI  - Enlarged subarachnoid spaces and intracranial hemorrhage in children with
      accidental head trauma.
AB  - OBJECTIVE Benign external hydrocephalus (BEH) is an enlargement of the
      subarachnoid spaces (SASs) that can be seen in young children. It is
      controversial whether children with BEH are predisposed to developing subdural
      hemorrhage (SDH) with or without trauma. This issue is clinically relevant as a
      finding of unexplained SDH raises concerns about child abuse and often prompts
      child protection and law enforcement investigations. METHODS This retrospective
      study included children (1-24 months of age) who underwent head CT scanning after
      an accidental fall of less than 6 feet. Head CT scans were reviewed, cranial
      findings were documented, and the SAS was measured and qualitatively evaluated.
      Enlarged SAS was defined as an extraaxial space (EAS) greater than 4 mm on CT
      scans. Clinical measurements of head circumference (HC) were noted, and the head
      circumference percentile was calculated. The relationship between enlarged SAS
      and HC percentile, and enlarged SAS and intracranial hemorrhage (ICH), were
      investigated using bivariate analysis. RESULTS Of the 110 children included in
      this sample, 23 had EASs greater than 4 mm. The mean patient age was 6.8 months
      (median 6.0 months). Thirty-four patients (30.9%) had ICHs, including
      subarachnoid/subpial (6.2%), subdural (6.2%), epidural (5.0%), and unspecified
      extraaxial hemorrhage (16.5%). Enlarged SAS was positively associated with
      subarachnoid/subpial hemorrhage; there was no association between enlarged SASs
      and either SDH or epidural hemorrhage. A larger SAS was positively associated
      with larger HC percentile; however, HC percentile was not independently
      associated with ICH. CONCLUSIONS Enlarged SAS was not associated with SDH, but
      was associated with other ICHs. The authors' findings do not support the theory
      that BEH predisposes children to SDH with minor accidental trauma.

PMID- 27885943
TI  - Cortical herniation through compressive subdural membrane in an infant with a
      history of a large bihemispheric subdural hematoma and subdural-peritoneal shunt:
      case report.
AB  - Cortical herniation through subdural membrane formation is a rare complication of
      chronic subdural fluid collections and may occur following subdural shunting. The
      authors present a unique case of progressive cortical herniation through a
      compressive subdural membrane that occurred concomitant with a functioning
      subdural-peritoneal shunt.

PMID- 27885944
TI  - Letter to the Editor: Ascenda catheter versus silicone catheter in intrathecal
      baclofen therapy.

PMID- 27885945
TI  - Clinical, imaging, and immunohistochemical characteristics of focal cortical
      dysplasia Type II extratemporal epilepsies in children: analyses of an
      institutional case series.
AB  - OBJECTIVE Focal cortical dysplasia (FCD) Type II is divided into 2 subgroups
      based on the absence (IIA) or presence (IIB) of balloon cells. In particular,
      extratemporal FCD Type IIA and IIB is not completely understood in terms of
      clinical, imaging, biological, and neuropathological differences. The aim of the
      authors was to analyze distinctions between these 2 formal entities and address
      clinical, MRI, and immunohistochemical features of extratemporal epilepsies in
      children. METHODS Cases formerly classified as Palmini FCD Type II nontemporal
      epilepsies were identified through the prospectively maintained epilepsy database
      at the British Columbia Children's Hospital in Vancouver, Canada. Clinical data,
      including age of seizure onset, age at surgery, seizure type(s) and frequency,
      affected brain region(s), intraoperative electrocorticographic findings, and
      outcome defined by Engel's classification were obtained for each patient.
      Preoperative and postoperative MRI results were reevaluated. H & E-stained tissue
      sections were reevaluated by using the 2011 International League Against Epilepsy
      classification system and additional immunostaining for standard cellular markers
      (neuronal nuclei, neurofilament, glial fibrillary acidic protein, CD68). Two
      additional established markers of pathology in epilepsy resection, namely, CD34
      and alpha-B crystallin, were applied. RESULTS Seven nontemporal FCD Type IIA and
      7 Type B cases were included. Patients with FCD Type IIA presented with an
      earlier age of epilepsy onset and slightly better Engel outcome. Radiology
      distinguished FCD Types IIA and IIB, in that Type IIB presented more frequently
      with characteristic cortical alterations. Nonphosphorylated neurofilament protein
      staining confirmed dysplastic cells in dyslaminated areas. The white-gray matter
      junction was focally blurred in patients with FCD Type IIB. alpha-B crystallin
      highlighted glial cells in the white matter and subpial layer with either of the
      2 FCD Type II subtypes and balloon cells in patients with FCD Type IIB. alpha-B
      crystallin positivity proved to be a valuable tool for confirming the
      histological diagnosis of FCD Type IIB in specimens with rare balloon cells or
      difficult section orientation. Distinct nonendothelial cellular CD34 staining was
      found exclusively in tissue from patients with MRI-positive FCD Type IIB.
      CONCLUSIONS Extratemporal FCD Types IIA and IIB in the pediatric age group
      exhibited imaging and immunohistochemical characteristics; cellular
      immunoreactivity to CD34 emerged as an especially potential surrogate marker for
      lesional FCD Type IIB, providing additional evidence that FCD Types IIA and IIB
      might differ in their etiology and biology. Although the sample number in this
      study was small, the results further support the theory that postoperative
      outcome-defined by Engel's classification-is multifactorial and determined by not
      only histology but also the extent of the initial lesion, its location in
      eloquent areas, intraoperative electrocorticographic findings, and achieved
      resection grade.

PMID- 27885947
TI  - QuickBrain MRI for the detection of acute pediatric traumatic brain injury.
AB  - OBJECTIVE The current gold-standard imaging modality for pediatric traumatic
      brain injury (TBI) is CT, but it confers risks associated with ionizing
      radiation. QuickBrain MRI (qbMRI) is a rapid brain MRI protocol that has been
      studied in the setting of hydrocephalus, but its ability to detect traumatic
      injuries is unknown. METHODS The authors performed a retrospective cohort study
      of pediatric patients with TBI who were undergoing evaluation at a single Level I
      trauma center between February 2010 and December 2013. Patients who underwent CT
      imaging of the head and qbMRI during their acute hospitalization were included.
      Images were reviewed independently by 2 neuroradiology fellows blinded to patient
      identifiers. Image review consisted of identifying traumatic mass lesions and
      their intracranial compartment and the presence or absence of midline shift. CT
      imaging was used as the reference against which qbMRI was measured. RESULTS A
      total of 54 patients met the inclusion criteria; the median patient age was 3.24
      years, 65% were male, and 74% were noted to have a Glasgow Coma Scale score of 14
      or greater. The sensitivity and specificity of qbMRI to detect any lesion were
      85% (95% CI 73%-93%) and 100% (95% CI 61%-100%), respectively; the sensitivity
      increased to 100% (95% CI 89%-100%) for clinically important TBIs as previously
      defined. The mean interval between CT and qbMRI was 27.5 hours, and approximately
      half of the images were obtained within 12 hours. CONCLUSIONS In this
      retrospective pilot study, qbMRI demonstrated reasonable sensitivity and
      specificity for detecting a lesion or injury seen with neuroimaging (radiographic
      TBI) and clinically important acute pediatric TBI.

PMID- 27885946
TI  - Epilepsy surgery in patients with autism.
AB  - OBJECTIVE The purpose of this study was to report outcomes of epilepsy surgery in
      56 consecutive patients with autism spectrum disorder. METHODS Medical records of
      56 consecutive patients with autism who underwent epilepsy surgery were reviewed
      with regard to clinical characteristics, surgical management, postoperative
      seizure control, and behavioral changes. RESULTS Of the 56 patients with autism,
      39 were male, 45 were severely autistic, 27 had a history of clinically
      significant levels of aggression and other disruptive behaviors, and 30 were
      considered nonverbal at baseline. Etiology of the epilepsy was known in 32 cases,
      and included structural lesions, medical history, and developmental and genetic
      factors. Twenty-nine patients underwent resective treatments (in 8 cases combined
      with palliative procedures), 24 patients had only palliative treatments, and 3
      patients had only subdural electroencephalography. Eighteen of the 56 patients
      had more than one operation. The mean age at surgery was 11 +/- 6.5 years (range
      1.5-35 years). At a mean follow-up of 47 +/- 30 months (range 2-117 months),
      seizure outcomes included 20 Engel Class I, 12 Engel Class II, 18 Engel Class
      III, and 3 Engel Class IV cases. The age and follow-up times are stated as the
      mean +/- SD. Three patients were able to discontinue all antiepileptic drugs
      (AEDs). Aggression and other aberrant behaviors observed in the clinical setting
      improved in 24 patients. According to caregivers, most patients also experienced
      some degree of improvement in daily social and cognitive function. Three patients
      had no functional or behavioral changes associated with seizure reduction, and 2
      patients experienced worsening of seizures and behavioral symptoms. CONCLUSIONS
      Epilepsy surgery in patients with autism is feasible, with no indication that the
      comorbidity of autism should preclude a good outcome. Resective and palliative
      treatments brought seizure freedom or seizure reduction to the majority of
      patients, although one-third of the patients in this study required more than one
      procedure to achieve worthwhile improvement in the long term, and few patients
      were able to discontinue all AEDs. The number of palliative procedures performed,
      the need for multiple interventions, and continued use of AEDs highlight the
      complex etiology of epilepsy in patients with autism spectrum disorder. These
      considerations underscore the need for continued analysis, review, and reporting
      of surgical outcomes in patients with autism, which may aid in better
      identification and management of surgical candidates. The reduction in aberrant
      behaviors observed in this series suggests that some behaviors previously
      attributed to autism may be associated with intractable epilepsy, and further
      highlights the need for systematic evaluation of the relationship between the
      symptoms of autism and refractory seizures.

PMID- 27885948
TI  - Urinary signature of pig carcasses with boar taint by liquid chromatography-high
      resolution mass spectrometry.
AB  - Boar taint is an offensive odour that can occur while cooking pork or pork
      products and is identified in some uncastrated male pigs that have reached
      puberty. It is widely held that boar taint is the result of the accumulation in
      back fat of two malodorous compounds: androstenone and skatole. The purpose of
      this study is to assess a mass spectrometry-based metabolomics strategy to
      investigate the metabolic profile of urine samples from pig carcasses presenting
      low (untainted) and high (tainted) levels of androstenone and skatole in back
      fat. Urine samples were analysed by LC-ESI(+)-HRMS. Discrimination between
      tainted and untainted animals was observed by the application of multivariate
      statistical analysis, which allowed candidate urinary biomarkers to be
      highlighted. These urinary metabolites were positively correlated to androstenone
      and skatole levels in back fat. Therefore, the study suggests that the
      measurement of these urinary metabolites might provide information with regard to
      androstenone and skatole levels in live pigs.

PMID- 27885949
TI  - Letter to the Editor: Whole-brain CT perfusion and subarachnoid hemorrhage.

PMID- 27885950
TI  - Randomized controlled trials in neurosurgery: an observational analysis of trial
      discontinuation and publication outcome.
AB  - OBJECTIVE This study aimed to determine the trial discontinuation and publication
      rate of randomized controlled trials (RCTs) in neurosurgery. METHODS Trials
      registered from 2000 to 2012 were identified on the website clinicaltrials.gov
      using a range of key words related to neurosurgery. Any trials that were actively
      recruiting or had unknown status were excluded. Included trials were assessed for
      whether they were discontinued early on the clinicaltrials.gov database; this
      included trials identified as withdrawn, suspended, or terminated in the
      database. For included trials, a range of parameters was identified including the
      subspecialty, primary country, study start date, type of intervention, number of
      centers, and funding status. Subsequently, a systematic search for published peer
      reviewed articles was undertaken. For trials that were discontinued early or were
      found to be unpublished, principal investigators were sent a querying email.
      RESULTS Sixty-four neurosurgical trials fulfilled our inclusion criteria. Of
      these 64, 26.6% were discontinued early, with slow or insufficient recruitment
      cited as the major reason (57%). Of the 47 completed trials, 14 (30%) remained
      unpublished. Discontinued trials showed a statistically significant higher chance
      of remaining unpublished (88%) compared with completed trials (p = 0.0002).
      Industry-funded trials had a higher discontinuation rate (31%) compared with non
      industry-funded trials (23%), but this result did not reach significance (p =
      0.57). Reporting of primary outcome measures was complete in 20 (61%) of 33
      trials. For secondary outcome measures, complete reporting occurred in only 11
      (33.3%) of 33. CONCLUSIONS More than a fifth (26.6%) of neurosurgical RCTs are
      discontinued early and almost a third of those that are completed remain
      unpublished. This result highlights significant waste of financial resources and
      clinical data.

PMID- 27885951
TI  - Retraction: Effect of atorvastatin on resolution of chronic subdural hematoma: a
      prospective observational study.

PMID- 27885952
TI  - Pretreatment growth rate as a predictor of tumor control following Gamma Knife
      radiosurgery for sporadic vestibular schwannoma.
AB  - OBJECTIVE Over the last 30 years, stereotactic radiosurgery (SRS) has become an
      established noninvasive treatment alternative for small- to medium-sized
      vestibular schwannoma (VS). This study aims to further define long-term SRS tumor
      control in patients with documented pretreatment tumor growth for whom
      conservative observation failed. METHODS A prospective clinical database was
      queried, and patients with sporadic VS who elected initial observation and
      subsequently underwent SRS after documented tumor growth between 2004 and 2014
      were identified. Posttreatment tumor growth or shrinkage was determined by a >= 2
      mm increase or decrease in maximum linear dimension, respectively. RESULTS Sixty
      eight patients met study inclusion criteria. The median pre- and posttreatment
      observation periods were 16 and 43.5 months, respectively. The median dose to the
      tumor margin was 13 Gy (range 12-14 Gy), and the median maximum dose was 26 Gy
      (range 24-28 Gy). At the time of treatment, 59 tumors exhibited extracanalicular
      (EC) extension, and 9 were intracanalicular (IC). Of the 59 EC VSs, 50 (85%)
      remained stable or decreased in size following treatment, and 9 (15%) enlarged by
      > 2 mm. Among EC tumors, the median pretreatment tumor growth rate was 2.08
      mm/year for tumors that decreased or were stable, compared with 3.26 mm/year for
      tumors that grew following SRS (p = 0.009). Patients who demonstrated a
      pretreatment growth rate of < 2.5 mm/year exhibited a 97% tumor control rate,
      compared with 69% for those demonstrating >= 2.5 mm/year of growth prior to SRS
      (p = 0.007). No other analyzed variables were found to predict tumor growth
      following SRS. CONCLUSIONS Overall, SRS administered using a marginal dose
      between 12-14 Gy is highly effective in treating VSs in which initial observation
      fails. Tumor control is achieved in 97% of VSs that exhibit slow (< 2.5 mm/year)
      pretreatment growth; however, SRS is less successful in treating tumors
      exhibiting rapid growth (>= 2.5 mm/year).

PMID- 27885953
TI  - Targeted sequencing of SMO and AKT1 in anterior skull base meningiomas.
AB  - OBJECTIVE Meningiomas located in the skull base are surgically challenging.
      Recent genomic research has identified oncogenic SMO and AKT1 mutations in a
      small subset of meningiomas. METHODS The authors performed targeted sequencing in
      a large cohort of patients with anterior skull base meningiomas (n = 62) to
      better define the frequency of SMO and AKT1 mutations in these tumors. RESULTS
      The authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62
      (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred
      in the olfactory groove. Meningiomas with an SMO mutation presented with
      significantly larger tumor volume (70.6 +/- 36.3 cm3) compared with AKT1-mutated
      (18.2 +/- 26.8 cm3) and wild-type (22.7 +/- 23.9 cm3) meningiomas, respectively.
      CONCLUSIONS Combined, these data demonstrate clinically actionable mutations in
      30% of anterior skull base meningiomas and suggest an association between SMO
      mutation status and tumor volume. Genotyping of SMO and AKT1 is likely to be high
      yield in anterior skull base meningiomas with available surgical tissue.

PMID- 27885954
TI  - Novel biomarker identification using metabolomic profiling to differentiate
      radiation necrosis and recurrent tumor following Gamma Knife radiosurgery.
AB  - OBJECTIVE Following an initial response of brain metastases to Gamma Knife
      radiosurgery, regrowth of the enhancing lesion as detected on MRI may represent
      either radiation necrosis (a treatment-related inflammatory change) or recurrent
      tumor. Differentiation of radiation necrosis from tumor is vital for management
      decision making but remains difficult by imaging alone. In this study, gas
      chromatography with time-of-flight mass spectrometry (GC-TOF) was used to
      identify differential metabolite profiles of the 2 tissue types obtained by
      surgical biopsy to find potential targets for noninvasive imaging. METHODS
      Specimens of pure radiation necrosis and pure tumor obtained from patient brain
      biopsies were flash-frozen and validated histologically. These formalin-free
      tissue samples were then analyzed using GC-TOF. The metabolite profiles of
      radiation necrosis and tumor samples were compared using multivariate and
      univariate statistical analysis. Statistical significance was defined as p <=
      0.05. RESULTS For the metabolic profiling, GC-TOF was performed on 7 samples of
      radiation necrosis and 7 samples of tumor. Of the 141 metabolites identified, 17
      (12.1%) were found to be statistically significantly different between comparison
      groups. Of these metabolites, 6 were increased in tumor, and 11 were increased in
      radiation necrosis. An unsupervised hierarchical clustering analysis found that
      tumor had elevated levels of metabolites associated with energy metabolism,
      whereas radiation necrosis had elevated levels of metabolites that were fatty
      acids and antioxidants/cofactors. CONCLUSIONS To the authors' knowledge, this is
      the first tissue-based metabolomics study of radiation necrosis and tumor.
      Radiation necrosis and recurrent tumor following Gamma Knife radiosurgery for
      brain metastases have unique metabolite profiles that may be targeted in the
      future to develop noninvasive metabolic imaging techniques.

PMID- 27885955
TI  - Editorial: Vestibular schwannoma radiosurgery: progression or pseudoprogression?

PMID- 27885956
TI  - Solitary tentorial sarcoid granuloma associated with Propionibacterium acnes
      infection: case report.
AB  - Sarcoidosis is a systemic granulomatous disease with unknown cause, which very
      rarely occurs exclusively in the central nervous system. The authors performed
      biopsy sampling of a mass that developed in the left tentorium cerebelli that
      appeared to be a malignant tumor. The mass was diagnosed as a sarcoid granuloma,
      which was confirmed with the onset of antibody reaction product against
      Propionibacterium acnes. Findings suggesting sarcoidosis to be an immune response
      to P. acnes infection have recently been reported, and they give insight for
      diagnosis and treatment of this disease. The authors report the possible first
      case that was confirmed with P. acnes infection in a meningeal lesion in solitary
      neurosarcoidosis.

PMID- 27885957
TI  - Visual pathway impairment by pituitary adenomas: quantitative diagnostics by
      diffusion tensor imaging.
AB  - OBJECTIVE Despite ample experience in surgical treatment of pituitary adenomas,
      little is known about objective indices that may reveal risk of visual impairment
      caused by tumor growth that leads to compression of the anterior visual pathways.
      This study aimed to explore diffusion tensor imaging (DTI) as a means for
      objective assessment of injury to the anterior visual pathways caused by
      pituitary adenomas. METHODS Twenty-three patients with pituitary adenomas,
      scheduled for transsphenoidal tumor resection, and 20 healthy control subjects
      were included in the study. A minimum suprasellar tumor extension of Grade 2-4,
      according to the SIPAP (suprasellar, infrasellar, parasellar, anterior, and
      posterior) scale, was required for inclusion. Neuroophthalmological examinations,
      conventional MRI, and DTI were completed in all subjects and were repeated 6
      months after surgery. Quantitative assessment of chiasmal lift, visual field
      defect (VFD), and DTI parameters from the optic tracts was performed. Linear
      correlations, group comparisons, and prediction models were done in controls and
      patients. RESULTS Both the degree of VFD and chiasmal lift were significantly
      correlated with the radial diffusivity (r = 0.55, p < 0.05 and r = 0.48, p <
      0.05, respectively) and the fractional anisotropy (r = -0.58, p < 0.05 and r = 
      0.47, p < 0.05, respectively) but not with the axial diffusivity. The axial
      diffusivity differed significantly between controls and patients with VFD, both
      before and after surgery (p < 0.05); however, no difference was found between
      patients with and without VFD. Based on the axial diffusivity and fractional
      anisotropy, a prediction model classified all patients with VFD correctly
      (sensitivity 1.0), 9 of 12 patients without VFD correctly (sensitivity 0.75), and
      17 of 20 controls as controls (specificity 0.85). CONCLUSIONS DTI could detect
      pathology and degree of injury in the anterior visual pathways that were
      compressed by pituitary adenomas. The correlation between radial diffusivity and
      visual impairment may reflect a gradual demyelination in the visual pathways
      caused by an increased tumor effect. The low level of axial diffusivity found in
      the patient group may represent early atrophy in the visual pathways, detectable
      on DTI but not by conventional methods. DTI may provide objective data, detect
      early signs of injury, and be an additional diagnostic tool for determining
      indication for surgery in cases of pituitary adenomas.

PMID- 27885958
TI  - Articulating reproductive justice through reparative justice: case studies of
      abortion in Great Britain and South Africa.
AB  - Public health and rights-based approaches to abortion advocacy are well
      established. Feminists are, however, increasingly using a broader framework of
      'reproductive justice', which considers the intersecting conditions that serve to
      enhance or hinder women's reproductive freedoms, including their capacities to
      decide about the outcome of their pregnancies. Nonetheless, reproductive justice
      approaches to abortion are, conceptually, relatively under-developed. We
      introduce a reparative justice approach as a method of further articulating the
      concept of reproductive justice. We first explain how this approach can be used
      to conceptualise safe, accessible and supportive abortion as a key element of
      reproductive justice in relation to the injustice of unwanted or unsupportable
      pregnancies. Using Ernesto Verdeja's critical theory of reparative justice and
      case studies of two countries (South Africa and Great Britain) where abortion is
      legal, we show how such an approach enables an analysis of reproductive justice
      within the specificities of particular contexts. We argue that both the rights
      based legal framework adopted in South Africa and the medicalised approach of
      British law have, in practice, limited reparative justice in these contexts. We
      discuss the implications of reparative justice for abortion advocacy.

PMID- 27885959
TI  - Bone marrow stromal cell sheets may promote axonal regeneration and functional
      recovery with suppression of glial scar formation after spinal cord transection
      injury in rats.
AB  - OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical
      potential as a therapeutic strategy in the treatment of spinal cord injury (SCI).
      Although a scaffold is sometimes used for retaining transplanted cells in damaged
      tissue, it is also known to induce redundant immunoreactions during the
      degradation processes. In this study, the authors prepared cell sheets made of
      BMSCs, which are transplantable without a scaffold, and investigated their
      effects on axonal regeneration, glial scar formation, and functional recovery in
      a completely transected SCI model in rats. METHODS BMSC sheets were prepared from
      the bone marrow of female Fischer 344 rats using ascorbic acid and were
      cryopreserved until the day of transplantation. A gelatin sponge (GS), as a
      control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal
      cord at the T-8 level. Axonal regeneration and glial scar formation were assessed
      2 and 8 weeks after transplantation by immunohistochemical analyses using anti
      Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively.
      Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale.
      RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after
      transplantation, but there was no significant difference in the number of Tuj1
      positive axons between the sheet- and GS-transplanted groups. At 8 weeks after
      transplantation, Tuj1-positive axons elongated across the sheet, and their
      numbers were significantly greater in the sheet group than in the GS group. The
      areas of GFAP-positive glial scars in the sheet group were significantly reduced
      compared with those of the GS group at both time points. Finally, hindlimb
      locomotor function was ameliorated in the sheet group at 4 and 8 weeks after
      transplantation. CONCLUSIONS The results of the present study indicate that an
      ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables
      autologous transplantation without requiring a scaffold.

PMID- 27885960
TI  - High-dose tranexamic acid reduces intraoperative and postoperative blood loss in
      posterior lumbar interbody fusion.
AB  - OBJECTIVE Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been
      reported to reduce blood loss in orthopedic surgery, but there have been few
      reports of its use in spine surgery. Previous studies included limitations in
      terms of different TXA dose regimens, different levels and numbers of fused
      segments, and different surgical techniques. Therefore, the authors decided to
      strictly limit TXA dose regimens, surgical techniques, and fused segments in this
      study. There have been no reports of using TXA for prevention of intraoperative
      and postoperative blood loss in posterior lumbar interbody fusion (PLIF). The
      purpose of the study was to evaluate the efficacy of high-dose TXA in reducing
      blood loss and its safety during single-level PLIF. METHODS The study was a
      nonrandomized, case-controlled trial. Sixty consecutive patients underwent single
      level PLIF at a single institution. The first 30 patients did not receive TXA.
      The next 30 patients received 2000 mg of intravenous TXA 15 minutes before the
      skin incision was performed and received the same dose again 16 hours after the
      surgery. Intra- and postoperative blood loss was compared between the groups.
      RESULTS There were no statistically significant differences in preoperative
      parameters of age, sex, body mass index, preoperative diagnosis, or operating
      time. The TXA group experienced significantly less intraoperative blood loss
      (mean 253 ml) compared with the control group (mean 415 ml; p < 0.01). The TXA
      group also had significantly less postoperative blood loss over 40 hours (mean
      321 ml) compared with the control group (mean 668 ml; p < 0.01). Total blood loss
      in the TXA group (mean 574 ml) was significantly lower than in the control group
      (mean 1080 ml; p < 0.01). From 2 hours to 40 hours, postoperative blood loss in
      the TXA group was consistently significantly lower. There were no perioperative
      complications, including thromboembolic events. CONCLUSIONS High-dose TXA
      significantly reduced both intra- and postoperative blood loss without causing
      any complications during or after single-level PLIF.

PMID- 27885961
TI  - INSIG2 polymorphism and weight gain, dyslipidemia and serum adiponectin in
      Finnish patients with schizophrenia treated with clozapine.
AB  - AIM: To investigate INSIG2's association with obesity, weight change and serum
      lipid profile during clozapine treatment. MATERIALS & METHODS: Subjects with
      schizophrenia (n = 190) were genotyped, identifying seven SNPs. Genetic risk
      scores (GRSs) were calculated to adiponectin, high-density lipoprotein
      cholesterol, triglycerides and weight gain. RESULTS: In the model for weight
      gain, SNPs rs12151787, rs17047733 and rs10490626 were selected. Explanatory
      variables were BMI (p = 5.05 * 10-5), age (p = 0.003) and GRS (p = 2.81 * 10-5, p
      = 0.0002 after permutation). No GRS resulted for adiponectin or high-density
      lipoprotein cholesterol. Rs2161829 and rs10490620 were selected for
      triglycerides; this GRS was insignificant after permutation. CONCLUSION: INSIG2
      plays a role in weight gain and obesity during clozapine treatment.

PMID- 27885962
TI  - Parental history of moderate to severe infantile malnutrition is associated with
      cognitive deficits in their adult offspring.
AB  - OBJECTIVES: We compared the IQ and academic achievement of the young adult
      offspring of parents malnourished in infancy and those of a healthy control group
      in order to test the hypothesis that the offspring of previously malnourished
      individuals would show IQ and academic deficits that could be related to reduced
      parental socioeconomic status. METHODS: We conducted a group comparison study
      based on a community sample in Barbados (Barbados Nutrition Study). Participants
      were adult children >=16 years of age whose parents had been malnourished during
      the first year of life (n = 64; Mean age 19.3 years; 42% male) or whose parents
      were healthy community controls (n = 50; Mean age 19.7 years; 48% male). The
      primary outcome was estimated IQ (Wechsler Abbreviated Scale of Intelligence); a
      secondary outcome was academic achievement (Wide Range Achievement Test - Third
      Edition). Data were analyzed using PROC MIXED with and without adjusting for
      parental socioeconomic status (Hollingshead Index of Social Position). RESULTS:
      IQ was reduced in the offspring of previously malnourished parents relative to
      the offspring of controls (9.8 point deficit; P < 0.01), but this difference was
      not explained by parental socioeconomic status or parental IQ. The magnitude of
      the group difference was smaller for basic academic skills and did not meet
      criteria for statistical significance. DISCUSSION: The deleterious impact of
      infant malnutrition on cognitive function may be transmitted to the next
      generation; however, this intergenerational effect does not appear to be
      explained by the reduced socioeconomic status or IQ of the parent generation.

PMID- 27885963
TI  - Coping with discrimination among HIV-positive Black men who have sex with men.
AB  - In the USA, HIV-positive Black men who have sex with men show large disparities
      in disease outcomes compared to other racial/ethnic and risk groups. This study
      examined the strategies that HIV-positive Black men who have sex with men use to
      cope with different types of discrimination. A total of 27 HIV-positive Black men
      who have sex with men participated in semi-structured interviews, which were
      transcribed verbatim and coded using thematic analysis by multiple raters. Major
      coping themes included reactive avoidance (using behaviours, cognitions and
      emotions to escape from discrimination), a common reaction to racism; proactive
      avoidance (avoiding situations in which discrimination is anticipated),
      manifested as selective disclosure of HIV-serostatus; external attribution for
      discrimination (versus self-blame), used more for sexual orientation and HIV
      discrimination; and social support-seeking, which most often emerged in response
      to racism. Active coping strategies, such as self-advocacy (countering
      discrimination directly or indirectly), were infrequently reported. Findings
      suggest a need for structural anti-discrimination interventions, in tandem with
      culturally congruent individual- or group-level interventions that aim to enhance
      men's existing adaptive coping strategies.

PMID- 27885964
TI  - Porphyromonas gingivalis Capsule-Mediated Coaggregation as a Virulence Factor in
      Mixed Infection With Fusobacterium nucleatum.
AB  - BACKGROUND: Porphyromonas gingivalis (Pg) capsule enables evasion from
      phagocytosis, invasion of keratinocytes, and bacterial survival. In mixed
      infection, the capsule also participates in coaggregation, which may lead to
      characteristic virulence not present in the monoinfection. The aim of this study
      is to evaluate the role of Pg capsule as a virulence factor in coaggregated mixed
      infection with Fusobacterium nucleatum (Fn). METHODS: Mixed infections containing
      Fn and non-capsulated or capsulated strains of Pg were compared with the same
      infection with lactose as coaggregation inhibitor. Murine experimental
      periodontitis was used to assess disease severity. Primary polymorphonuclear
      leukocytes and keratinocytes were used to examine phagocytosis and bacterial
      invasion, respectively. RESULTS: Mixed infection with capsulated Pg augmented
      alveolar bone loss compared with that of mixed infection with non-capsulated Pg.
      Addition of lactose led to attenuation of bone loss in the capsulated mixed
      infection and to intensification of bone loss in the non-capsulated mixed
      infection. In the latter mixed infection, Fn evaded phagocytosis, whereas in the
      capsulated mixed infection Pg displayed a greater capacity for invasion of
      keratinocytes. CONCLUSIONS: Pg capsule was found to serve as a unique virulence
      factor in mixed infection with Fn. Capsule-dependent coaggregation led to
      augmented invasion of Pg and may be responsible for the severity of disease after
      mixed infection with Fn.

PMID- 27885965
TI  - Parameters That Improve Cleaning Efficiency of Subgingival Air Polishing on
      Titanium Implant Surfaces: An In Vitro Study.
AB  - BACKGROUND: This study aims to reveal how air polishing behaves on a titanium
      surface by evaluating the size and shape of the cleaned area and the influence of
      different device settings, probing depths, and cleaning movements. METHODS: Forty
      eight titanium sandblasted large-grit acid-etched surface film-coated disks were
      treated with an air abrasive system using a subgingival plastic nozzle. Two
      subgingival models were used: open-ended (step 1) and defined-size (step 2). In
      step 1, the most effective parameters were investigated by 5-second static
      applications under different settings. In step 2, the best settings were used for
      dynamic application to test influence of different movements (up-down, slowly up,
      rotation). For both steps, powder and water consumption and total cleaned area
      were calculated. RESULTS: Air pressure was the main factor with the strongest
      effect on cleaning. Increasing air pressure extended cleaning area. Other
      factors, such as nozzle depth and excessive powder flow amount, had weak
      influence. Cleaning effect reached deeper than the nozzle physically reached.
      Step 2 showed that there was no significant difference between different nozzle
      movements; however, cleaning efficiency decreased significantly without movement.
      CONCLUSIONS: For the most effective clinical use of air polishing, it should be
      applied with high pressure, deep insertion of nozzle, and enough water flow.
      Additionally, the nozzle has to be moved to get the best cleaning effect.

PMID- 27885967
TI  - Corrigendum.

PMID- 27885969
TI  - 36th International Symposium on Intensive Care and Emergency Medicine : Brussels,
      Belgium. 15-18 March 2016.

PMID- 27885966
TI  - Erbium, Chromium:Yttrium-Scandium-Gallium-Garnet Laser Effectively Ablates Single
      Species Biofilms on Titanium Disks Without Detectable Surface Damage.
AB  - BACKGROUND: Increasing evidence implicates biofilms, consisting of species such
      as Porphyromonas gingivalis (Pg), in the etiology of peri-implantitis. Multiple
      approaches to ablate biofilms on failing implants have been proposed and include
      use of lasers, most recently the erbium, chromium:yttrium-scandium-gallium-garnet
      (Er,Cr:YSGG) laser. The purpose of this study is to establish an in vitro single
      species biofilm model on implant surfaces and determine power settings of the
      Er,Cr:YSGG laser that remove biofilm without causing physical damage to disks.
      METHODS: Single-species biofilms consisting of Pg strain 381 were grown on
      titanium disks, including: 1) sandblasted, large-grit, acid-etched (SLA); 2)
      calcium phosphate nano-coated (CaP); 3) anodized; or 4) machined surfaces. Power
      settings from 0 to 1.5 W using an Er,Cr:YSGG laser equipped with radial firing
      tip were used. Biofilm formation/removal was quantitated using confocal and
      scanning electron microscopy. Surface changes in temperature, microroughness, and
      water contact angle were analyzed. RESULTS: Results show confluent Pg biofilm
      coating all disk surfaces. The laser removed biofilms from all surfaces, with CaP
      and SLA surfaces requiring power setting of 1.0 to 1.5 W for ablation of bacteria
      coating the disks. Within this power range, and with water spray, there were no
      changes in surface temperature, surface roughness, or contact angle on any
      surfaces tested. CONCLUSION: The Er,Cr:YSGG laser with radial firing tip and
      water spray was able to effectively ablate >=95% of biofilm on all types of
      tested titanium surfaces, using clinically relevant power settings, without
      causing measurable physical changes to surfaces.

PMID- 27885968
TI  - Possible approaches to CYP2C9-guided prescription of sulfonylureas in Russia.
AB  - AIM: To evaluate a possible role of CYP2C9 genotyping for sulfonylureas (SUs)
      prescription in Russia. MATERIALS & METHODS: We have collected the current data
      on correlation between SUs pharmacodynamics and CYP2C9 polymorphisms. We have
      evaluated the frequency of CYP2C9 polymorphisms in Russia by reviewing the
      literature published from 2004 to 2015 on Russian CYP2C9. RESULTS: The genotype
      *1/*1, which confers risk for treatment failure, has a higher frequency (81.92%)
      in the non-Caucasians than that (64.92%) in the Caucasians. The Caucasians have a
      frequency (3.58%) of the poor metabolizers (*2/*2, *2/*3 and *3/*3) eight-times
      higher than that (0.44%) in the non-Caucasians, predisposing an increased risk of
      hypoglycemia. CONCLUSION: Considering the received data and the existed knowledge
      on CYP2C9 influence on SUs pharmacokinetics and pharmacodynamics, we propose a
      possible approach to CYP2C9-guided SUs prescription for Russians.

PMID- 27885970
TI  - Cpt1a gene expression in peripheral blood mononuclear cells as an early biomarker
      of diet-related metabolic alterations.
AB  - BACKGROUND: Research on biomarkers that provide early information about the
      development of future metabolic alterations is an emerging discipline. Gene
      expression analysis in peripheral blood mononuclear cells (PBMC) is a promising
      tool to identify subjects at risk of developing diet-related diseases. OBJECTIVE:
      We analysed PBMC expression of key energy homeostasis-related genes in a time
      course analysis in order to find out early markers of metabolic alterations due
      to sustained intake of high-fat (HF) and high-protein (HP) diets. DESIGN: We
      administered HF and HP diets (4 months) to adult Wistar rats in isocaloric
      conditions to a control diet, mainly to avoid overweight associated with the
      intake of hyperlipidic diets and, thus, to be able to characterise markers of
      metabolically obese normal-weight (MONW) syndrome. PBMC samples were collected at
      different time points of dietary treatment and expression of relevant energy
      homeostatic genes analysed by real-time reverse transcription-polymerase chain
      reaction. Serum parameters related with metabolic syndrome, as well as fat
      deposition in liver, were also analysed. RESULTS: The most outstanding results
      were those obtained for the expression of the lipolytic gene carnitine
      palmitoyltransferase 1a (Cpt1a). Cpt1a expression in PBMC increased after only 1
      month of exposure to both unbalanced diets, and this increased expression was
      maintained thereafter. Interestingly, in the case of the HF diet, Cpt1a
      expression was altered even in the absence of increased body weight but
      correlated with alterations such as higher insulin resistance, alteration of
      serum lipid profile and, particularly, increased fat deposition in liver, a
      feature characteristic of metabolic syndrome, which was even observed in animals
      fed with HP diet. CONCLUSIONS: We propose Cpt1a gene expression analysis in PBMC
      as an early biomarker of metabolic alterations associated with MONW phenotype due
      to the intake of isocaloric HF diets, as well as a marker of increased risk of
      metabolic diseases associated with the intake of HF or HP diets.

PMID- 27885971
TI  - "A magical little pill that will relieve you of your womanly issues": What young
      women say about menstrual suppression.
AB  - Perceptions of menstruation by media discourses portray this bodily function to
      be messy, inconvenient, and as an unnecessary phenomenon to be controlled or
      possibly eliminated. Commercials shown on YouTube targeted toward young women
      suggest that having a monthly period is not healthy and a lifestyle that is
      menses free is both pharmacologically available and recommended in order to live
      a fuller life. We explored the meanings attached to online menstrual suppression
      commercials with 10 women aged between 18 and 25. In-depth open-ended interviews
      were conducted over a 10-month period in 2014 after each participant viewed three
      menstrual suppression online advertisements. Feminist critical discourse was used
      for analysis with both authors coding for inter-rater reliability recognizing how
      our age difference and relationship as mother and daughter informed our
      interpretation. An overarching theme of tension emerged from the interviews with
      participants feeling detached due to the gendered stereotypes the commercials
      used to frame menstruation as compared to their own lived experience. Meanings
      associated with the menstrual suppression commercials were contrary to the
      participants' lived experience of menstruation as a healthy process not a
      detrimental one to their well-being as suggested by the commercials. Subliminal
      messages within the advertisements were identified as reinforcing gender bias and
      prejudices, including those associated with femininity. Despite attempting to
      emulate popular culture, the menstrual suppression advertisements were largely
      dismissed by this group of participants as undermining their intelligence and of
      intentionally creating divisive binaries between groups of women. This study
      suggests that historical bias and stereotypical prejudices were identified by
      this group of young women within the marketing of menstrual suppression products
      and, as such, were dismissed as inauthentic to the menstruation experience
      reflecting a form of menstrual activism.

PMID- 27885972
TI  - Protecting the confidentiality and security of personal health information in low
      and middle-income countries in the era of SDGs and Big Data.
AB  - BACKGROUND: As increasing amounts of personal information are being collected
      through a plethora of electronic modalities by statutory and non-statutory
      organizations, ensuring the confidentiality and security of such information has
      become a major issue globally. While the use of many of these media can be
      beneficial to individuals or populations, they can also be open to abuse by
      individuals or statutory and non-statutory organizations. Recent examples include
      collection of personal information by national security systems and the
      development of national programs like the Chinese Social Credit System. In many
      low- and middle-income countries, an increasing amount of personal health
      information is being collected. The collection of personal health information is
      necessary, in order to develop longitudinal medical records and to monitor and
      evaluate the use, cost, outcome, and impact of health services at facility, sub
      national, and national levels. However, if personal health information is not
      held confidentially and securely, individuals with communicable or non
      communicable diseases (NCDs) may be reluctant to use preventive or therapeutic
      health services, due to fear of being stigmatized or discriminated against. While
      policymakers and other stakeholders in these countries recognize the need to
      develop and implement policies for protecting the privacy, confidentiality and
      security of personal health information, to date few of these countries have
      developed, let alone implemented, coherent policies. The global HIV response
      continues to emphasize the importance of collecting HIV-health information,
      recently re-iterated by the Fast Track to End AIDS by 2030 program and the recent
      changes in the Guidelines on When to Start Antiretroviral Therapy and on Pre
      exposure Prophylaxis for HIV. The success of developing HIV treatment cascades in
      low- and middle-income countries will require the development of National Health
      Identification Systems. The success of programs like Universal Health Coverage,
      under the recently ratified Sustainable Development Goals is also contingent on
      the availability of personal health information for communicable and non
      communicable diseases. DESIGN: Guidance for countries to develop and implement
      their own guidelines for protecting HIV-information formed the basis of
      identifying a number of fundamental principles, governing the areas of privacy,
      confidentiality and security. The use of individual-level data must balance
      maximizing the benefits from their most effective and fullest use, and minimizing
      harm resulting from their malicious or inadvertent release. DISCUSSION: These
      general principles are described in this paper, as along with a bibliography
      referring to more detailed technical information. A country assessment tool and
      user's manual, based on these principles, have been developed to support
      countries to assess the privacy, confidentiality, and security of personal health
      information at facility, data warehouse/repository, and national levels. The
      successful development and implementation of national guidance will require
      strong collaboration at local, regional, and national levels, and this is a pre
      condition for the successful implementation of a range of national and global
      programs. CONCLUSION: This paper is a call for action for stakeholders in low-
      and middle-income countries to develop and implement such coherent policies and
      provides fundamental principles governing the areas of privacy, confidentiality,
      and security of personal health information being collected in low- and middle
      income countries.

PMID- 27885973
TI  - Leprosy trends at a tertiary care hospital in Mumbai, India, from 2008 to 2015.
AB  - BACKGROUND: Leprosy remains an important cause of preventable disabilities. After
      the advent of multidrug therapy, new leprosy cases have come down dramatically.
      Despite this achievement, India, which contributes 60% of the global leprosy
      burden, faces some challenges to eliminate the disease, including active
      transmission in the community and delayed diagnosis of leprosy patients.
      OBJECTIVES: The objectives of the study were 1) to determine sociodemographic and
      clinical characteristics of newly diagnosed adults and children (less than 15
      years) with leprosy and their trends over time (2008-2015) and 2) to describe the
      profile of surgical procedures among leprosy patients registered for
      reconstructive surgeries during 2006-2015. DESIGN: Retrospective descriptive
      study was conducted involving a record review of new patients with leprosy
      registered in Vimala Dermatological Centre, Mumbai. RESULTS: A total of 578 new
      leprosy cases were registered in the hospital during 2008-2015. There has been a
      steady increase in the trend of child cases (less than 15 years) registered in
      the facility (from 3% in 2008 to 18% in 2015), x2=12.11, p<0.01. The majority of
      the patients (68%) were migrants of Uttar Pradesh and Bihar. CONCLUSIONS:
      Targeting children and migrants and ensuring early diagnosis and treatment
      initiation are essential components for leprosy elimination in an urban
      metropolis in India.

PMID- 27885974
TI  - The Academy Research Grants in Hearing and Balance.

PMID- 27885975
TI  - Hearing Benefit and Rated Satisfaction in Children with Unilateral Conductive
      Hearing Loss Using a Transcutaneous Magnetic-Coupled Bone-Conduction Hearing Aid.
AB  - BACKGROUND: Bilateral hearing is important for learning, development, and
      function in complex everyday environments. Children with conductive and mixed
      hearing loss (HL) have been treated for years with percutaneous coupling through
      an abutment, which achieves powerful output, but the implant site is susceptible
      to skin reactions and trauma. To overcome these complications, transcutaneous
      magnetic coupling systems were recently introduced. PURPOSE: The purpose of the
      study was to evaluate whether the new transcutaneous magnetic coupling is an
      effective coupling paradigm for bone-conduction hearing aids (BCHAs). We
      hypothesized that magnetic coupling will (1) have limited adverse events, (2)
      provide adequate functional gain, (3) improve spatial hearing and aid listening
      in everyday situations, and (4) provide satisfactory outcomes to children and
      their families given one normal hearing ear. RESEARCH DESIGN: Retrospective
      analysis of audiological outcomes in a tertiary academic pediatric hospital.
      STUDY SAMPLE: Nine children aged 5-17 yr with permanent unilateral conductive HL
      (UCHL) or mixed HL were implanted with a transcutaneous magnet-retained BCHA.
      Average hearing thresholds of the better and implanted ears were 12.3 +/- 11.5 dB
      HL and 69.1 +/- 11.6 dB HL, respectively, with a 59.4 +/- 4.8 dB (mean +/-
      standard deviation) conductive component. DATA COLLECTION AND ANALYSIS: Data were
      extracted from audiology charts of the children with permanent UCHL or mixed HL
      who qualified for a surgically retained BCHA and agreed to the magnetic coupling.
      Outcomes were collected from the 3- to 9-mo follow-up appointments, and included
      surgical complications, aided audiometric thresholds with varying magnet
      strength, speech performance in quiet and noise, and patient-rated benefit and
      satisfaction using questionnaires. Repeated measures analysis of variance was
      used to analyze audiometric outcomes, and nonparametric tests were used to
      evaluate rated benefit and satisfaction. RESULTS: All nine children tolerated the
      device and only one child had discomfort at the wound site. Similar access to
      sound was achieved regardless of magnet strength. Speech performance did not
      significantly improve in quiet or noise conditions with +10 and +5 dB signal-to
      noise ratio. Children benefited from spatially separating the noise from the
      speech signal, regardless of whether the noise was directed to the implanted or
      better ear. When wearing the BCHA, the children reported satisfaction and
      significant implant benefit, particularly in background noise, but at the expense
      of increased aversiveness to sound. CONCLUSIONS: Our findings, therefore,
      indicate that providing a transcutaneous magnetic-coupled BCHA to children who
      have UCHL or mixed HL provides benefit on some objective measures of bilateral
      hearing, as well as some subjective benefit in noise and everyday situations.

PMID- 27885976
TI  - Negative Effect of Acoustic Panels on Listening Effort in a Classroom
      Environment.
AB  - BACKGROUND: Acoustic panels are used to lessen the pervasive effects of noise and
      reverberation on speech understanding in a classroom environment. These panels,
      however, predominately absorb high-frequency energy important to speech
      understanding. Therefore, a classroom environment treated with acoustic panels
      might negatively influence the transmission of the target signal, resulting in an
      increase in listening effort exerted by the listener. PURPOSE: Acoustic panels
      were installed in a public school environment that did not meet the ANSI
      recommended guidelines for classroom design. We assessed the modifications to the
      acoustic climate by quantifying the effect of (1) acoustic panel (i.e., without,
      with) on the transmission of a standardized target signal at different seat
      positions (i.e., A-D) using the Speech Transmission Index (STI) and (2) acoustic
      panel and seat position on listening-effort performance in a group of third-grade
      students having normal-hearing sensitivity using a dual-task paradigm. RESEARCH
      DESIGN: STI measurements are described qualitatively. We used a repeated-measures
      randomized design to assess listening-effort performance of monosyllabic words in
      a primary task and digit recall in a secondary task for the independent variables
      of acoustic panel and seat position. STUDY SAMPLE: Twenty-seven, third-grade
      students (12 males, 15 females), ranging in age from 8.3 to 9.4 yr (mean = 8.7
      yr, standard deviation = 0.7), participated in this study. DATA COLLECTION AND
      ANALYSIS: Qualitatively, we performed STI measurements under both testing
      conditions (i.e., panel and seat location). For the primary task of the dual-task
      paradigm, participants heard a ten-item list of monosyllabic words (i.e., ten
      words per list) recorded through a manikin in the classroom environment without
      and with acoustic panels and at different seat positions. Participants were asked
      to repeat each word exactly as it was heard. During the secondary task,
      participants were shown a single, random string of five digits before the
      presentation of the monosyllabic words. After each list in the primary task was
      completed, participants were asked to recall the string of five digits verbatim.
      RESULTS: Word-recognition and digit-recall performance decreased with the
      presence of acoustic panels and as the distance from the target signal to a given
      seat location increased. The results were validated using the STI, as indicated
      by a decrease in the transmission of the target signal in the presence of
      acoustic panel and as the distance to a given seat location increased.
      CONCLUSIONS: The inclusion of acoustic panels reduced the negative effects of
      noise and reverberation in a classroom environment, resulting in an acoustic
      climate that complied with the ANSI-recommended guidelines for classroom design.
      Results, however, revealed that participants required an increased amount of
      mental effort when the classroom was modified with acoustic treatment compared to
      no acoustic treatment. Independent of acoustic treatment, mental effort was
      greatest at seat locations beyond the critical distance (CD). With the addition
      of acoustic panels, mental effort was found to increase significantly at seat
      locations beyond the CD compared to the unmodified room condition. Overall,
      results indicate that increasing the distance between the teacher and child has a
      detrimental impact on mental effort and, ultimately, academic performance.

PMID- 27885977
TI  - Preference to Patient-Centeredness in Undergraduate Audiology Students in
      Portugal.
AB  - BACKGROUND: In health care, the model of patient-centered care is growing; and
      improved outcomes have been linked to patient-centeredness. Practicing
      audiologists have been found to strongly prefer a patient-centered approach as
      years in practice increase. It is unknown whether patient-centeredness begins
      during education and training. PURPOSE: The current study was aimed at
      understanding the preference to patient-centeredness in undergraduate audiology
      students in Portugal. RESEARCH DESIGN: The study used a cross-sectional survey
      design. STUDY SAMPLE: One hundred and thirty-seven undergraduate audiology
      students completed patient-practitioner orientation scale (PPOS) and provided
      some demographic details. DATA COLLECTION AND ANALYSIS: The data were analyzed
      using one-way analysis of variance and one-sample t tests. RESULTS: A significant
      difference was found for sharing subscale (p <= 0.001), caring subscale (p =
      0.033), and the PPOS full scale (p <= 0.001) among different undergraduate
      groups. Further, post hoc tests showed that the difference between year 1 and
      with years 2, 3, and 4 were significant for sharing subscale and PPOS full scale,
      but not for caring subscale. No significant differences were observed among the
      years 2, 3, and 4 for sharing subscale, caring subscale, and for PPOS full scale.
      When compared audiologists' preferences from a previous study on audiologists
      with students' preferences in the current study, significant difference for both
      subscales and full scale was found between year 1 students and audiologists (p <=
      0.001), with higher preference to patient-centeredness was reported by qualified
      audiologists. Also, significant difference was found between audiologists and
      overall undergraduate group for caring subscale (p = 0.001). CONCLUSIONS: The
      current study suggests that audiology education influences preference to patient
      centeredness. Within a year of undergraduate coursework, students tend to develop
      high preference to patient-centeredness, which stays stable during four years of
      undergraduate studies. These results provide useful insights to audiology
      education and training, particularly in the context of audiological
      rehabilitation.

PMID- 27885978
TI  - Factors Affecting Daily Cochlear Implant Use in Children: Datalogging Evidence.
AB  - BACKGROUND: Children with profound hearing loss can gain access to sound through
      cochlear implants (CIs), but these devices must be worn consistently to promote
      auditory development. Although subjective parent reports have identified several
      factors limiting long-term CI use in children, it is also important to understand
      the day-to-day issues which may preclude consistent device use. In the present
      study, objective measures gathered through datalogging software were used to
      quantify the following in children: (1) number of hours of CI use per day, (2)
      practical concerns including repeated disconnections between the external
      transmission coil and the internal device (termed "coil-offs"), and (3) listening
      environments experienced during daily use. PURPOSE: This study aimed to (1)
      objectively measure daily CI use and factors influencing consistent device use in
      children using one or two CIs and (2) evaluate the intensity levels and types of
      listening environments children are exposed to during daily CI use. RESEARCH
      DESIGN: Retrospective analysis. STUDY SAMPLE: Measures of daily CI use were
      obtained from 146 pediatric users of Cochlear Nucleus 6 speech processors. The
      sample included 5 unilateral, 40 bimodal, and 101 bilateral CI users (77
      simultaneously and 24 sequentially implanted). DATA COLLECTION AND ANALYSIS:
      Daily CI use, duration, and frequency of coil-offs per day, and the time spent in
      multiple intensity ranges and environment types were extracted from the datalog
      saved during clinic appointments. Multiple regression analyses were completed to
      predict daily CI use based on child-related demographic variables, and to
      evaluate the effects of age on coil-offs and environment acoustics. RESULTS:
      Children used their CIs for 9.86 +/- 3.43 hr on average on a daily basis, with
      use exceeding 9 hr per day in ~64% of the children. Daily CI use reduced
      significantly with increasing durations of coil-off (p = 0.027) and increased
      significantly with longer CI experience (p < 0.001) and pre-CI acoustic
      experience (p < 0.001), when controlled for the child's age. Total time in sound
      (sum of CI and pre-CI experience) was positively correlated with CI use (r =
      0.72, p < 0.001). Longer durations of coil-off were associated with higher
      frequency of coil-offs (p < 0.001). The frequency of coil-offs ranged from 0.99
      to 594.10 times per day and decreased significantly with age (p < 0.001). Daily
      CI use and frequency of coil-offs did not vary significantly across known
      etiologies. Listening environments of all children typically ranged between 50
      and 70 dBA. Children of all ages were exposed to speech in noisy environments.
      Environment classified as "music" was identified more often in younger children.
      CONCLUSIONS: The majority of children use their CIs consistently, even during the
      first year of implantation. The frequency of coil-offs is a practical challenge
      in infants and young children, and demonstrates the need for improved coil
      retention methods for pediatric use. Longer hearing experience and shorter coil
      off time facilitates consistent CI use. Children are listening to speech in noisy
      environments most often, thereby indicating a need for better access to binaural
      cues, signal processing, and stimulation strategies to aid listening. Study
      findings could be useful in parent counseling of young and/or new CI users.

PMID- 27885979
TI  - Gender Differences in Audiological Findings and Hearing Aid Benefit in 255
      Individuals with Auditory Neuropathy Spectrum Disorder: A Retrospective Study.
AB  - BACKGROUND: There are many studies reported in the literature that have
      summarized audiological findings and possible rehabilitation in individuals with
      auditory neuropathy spectrum disorder (ANSD). However, there are very few studies
      that have attempted to delineate the gender differences in audiological
      characteristics and hearing aid benefit in individuals with ANSD. PURPOSE: The
      study aimed to explore the differences between males and females in terms of
      demographic details, audiogram, speech identification scores, otoacoustic
      emissions, acoustic reflexes, long latency responses, and hearing aid benefit.
      RESEARCH DESIGN: A retrospective study. STUDY SAMPLE: A total of 255 individuals
      diagnosed with ANSD were selected for the study. The study included 137 females
      and 88 males. DATA COLLECTION AND ANALYSIS: The demographic details, results of
      diagnostic audiological testing, and hearing aid benefit were analyzed
      retrospectively. The differences in findings across gender were compared.
      RESULTS: The study shows that females have a relatively higher degree of hearing
      loss and that the majority of females show a rising type of audiometric
      configuration. The study shows that females have poorer speech perception
      abilities and experience limited benefits from hearing aids compared to males.
      CONCLUSIONS: The results of the study show that there are gender differences in
      audiological findings and hearing aid benefits in individuals with ANSD. However,
      well-controlled prospective studies are essential to confirm the results obtained
      and to identify the possible mechanisms underlying the gender differences.

PMID- 27885980
TI  - A Revision Surgery for Cochlear Implantation in a Case of Incomplete Partition
      Type I.
AB  - BACKGROUND: Patients with cochlear malformations were long considered poor
      candidates for cochlear implantation (CI), and surgical approaches different than
      the standard facial recess approach were used to access the inner ear. There is
      no previous long-term follow-up of a patient with significantly malformed inner
      ear operated through an untraditional route and requiring a revision surgery.
      PURPOSE: This case provides a long-term follow-up from the initial surgery, a
      short-term follow-up from the revision surgery, and it illustrates the evolving
      classification of inner ear malformations as well as the potential problems
      associated with nonstandard approaches to the cochlea. RESEARCH DESIGN: A case
      report. INTERVENTION: Herein, we report a case of revision CI in a patient with
      incomplete partition type I, through the round window via a facial recess
      approach, 18 yr after an initial implantation via a transmastoid labyrinthotomy
      approach. RESULTS: The patient had an uncomplicated surgery, and after
      activation, she noted auditory perception on all electrodes without facial
      stimulation. A sound field sound awareness threshold was obtained at 15 dB HL.
      CONCLUSIONS: As the prior generation of cochlear implant recipients ages, the
      probability of a revision surgery for various causes increases. Cochlear implant
      surgeons should be aware of the potential pitfalls associated in these often
      challenging cases.

PMID- 27885984
TI  - A new trick for an old lipid.
AB  - Cholesterol can regulate the Hedgehog signalling pathway by directly binding to a
      receptor on the cell surface.

PMID- 27885983
TI  - Klp10A, a stem cell centrosome-enriched kinesin, balances asymmetries in
      Drosophila male germline stem cell division.
AB  - Asymmetric stem cell division is often accompanied by stereotypical inheritance
      of the mother and daughter centrosomes. However, it remains unknown whether and
      how stem cell centrosomes are uniquely regulated and how this regulation may
      contribute to stem cell fate. Here we identify Klp10A, a microtubule
      depolymerizing kinesin of the kinesin-13 family, as the first protein enriched in
      the stem cell centrosome in Drosophila male germline stem cells (GSCs). Depletion
      of klp10A results in abnormal elongation of the mother centrosomes in GSCs,
      suggesting the existence of a stem cell-specific centrosome regulation program.
      Concomitant with mother centrosome elongation, GSCs form asymmetric spindle,
      wherein the elongated mother centrosome organizes considerably larger half
      spindle than the other. This leads to asymmetric cell size, yielding a smaller
      differentiating daughter cell. We propose that klp10A functions to counteract
      undesirable asymmetries that may result as a by-product of achieving asymmetries
      essential for successful stem cell divisions.

PMID- 27885985
TI  - Connectivity map of bipolar cells and photoreceptors in the mouse retina.
AB  - In the mouse retina, three different types of photoreceptors provide input to 14
      bipolar cell (BC) types. Classically, most BC types are thought to contact all
      cones within their dendritic field; ON-BCs would contact cones exclusively via so
      called invaginating synapses, while OFF-BCs would form basal synapses. By mining
      publically available electron microscopy data, we discovered interesting
      violations of these rules of outer retinal connectivity: ON-BC type X contacted
      only ~20% of the cones in its dendritic field and made mostly atypical non
      invaginating contacts. Types 5T, 5O and 8 also contacted fewer cones than
      expected. In addition, we found that rod BCs received input from cones, providing
      anatomical evidence that rod and cone pathways are interconnected in both
      directions. This suggests that the organization of the outer plexiform layer is
      more complex than classically thought.

PMID- 27885987
TI  - Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in
      axolotls.
AB  - Axolotls are unique in their ability to regenerate the spinal cord. However, the
      mechanisms that underlie this phenomenon remain poorly understood. Previously, we
      showed that regenerating stem cells in the axolotl spinal cord revert to a
      molecular state resembling embryonic neuroepithelial cells and functionally
      acquire rapid proliferative divisions (Rodrigo Albors et al., 2015). Here, we
      refine the analysis of cell proliferation in space and time and identify a high
      proliferation zone in the regenerating spinal cord that shifts posteriorly over
      time. By tracking sparsely-labeled cells, we also quantify cell influx into the
      regenerate. Taking a mathematical modeling approach, we integrate these
      quantitative datasets of cell proliferation, neural stem cell activation and cell
      influx, to predict regenerative tissue outgrowth. Our model shows that while cell
      influx and neural stem cell activation play a minor role, the acceleration of the
      cell cycle is the major driver of regenerative spinal cord outgrowth in axolotls.

PMID- 27885989
TI  - Correction of: Sleep Quality Prediction From Wearable Data Using Deep Learning.
AB  - [This corrects the article DOI: 10.2196/mhealth.6562.].

PMID- 27885986
TI  - Mapping out Min protein patterns in fully confined fluidic chambers.
AB  - The bacterial Min protein system provides a major model system for studying
      reaction-diffusion processes in biology. Here we present the first in vitro study
      of the Min system in fully confined three-dimensional chambers that are
      lithography-defined, lipid-bilayer coated and isolated through pressure valves.
      We identify three typical dynamical behaviors that occur dependent on the
      geometrical chamber parameters: pole-to-pole oscillations, spiral rotations, and
      traveling waves. We establish the geometrical selection rules and show that,
      surprisingly, Min-protein spiral rotations govern the larger part of the
      geometrical phase diagram. Confinement as well as an elevated temperature reduce
      the characteristic wavelength of the Min patterns, although even for confined
      chambers with a bacterial-level viscosity, the patterns retain a ~5 times larger
      wavelength than in vivo. Our results provide an essential experimental base for
      modeling of intracellular Min gradients in bacterial cell division as well as,
      more generally, for understanding pattern formation in reaction-diffusion
      systems.

PMID- 27885990
TI  - Correction: Validation of a preclinical model for assessment of drug efficacy in
      melanoma.

PMID- 27885988
TI  - Global mapping of highly pathogenic avian influenza H5N1 and H5Nx clade 2.3.4.4
      viruses with spatial cross-validation.
AB  - Global disease suitability models are essential tools to inform surveillance
      systems and enable early detection. We present the first global suitability model
      of highly pathogenic avian influenza (HPAI) H5N1 and demonstrate that reliable
      predictions can be obtained at global scale. Best predictions are obtained using
      spatial predictor variables describing host distributions, rather than land use
      or eco-climatic spatial predictor variables, with a strong association with
      domestic duck and extensively raised chicken densities. Our results also support
      a more systematic use of spatial cross-validation in large-scale disease
      suitability modelling compared to standard random cross-validation that can lead
      to unreliable measure of extrapolation accuracy. A global suitability model of
      the H5 clade 2.3.4.4 viruses, a group of viruses that recently spread extensively
      in Asia and the US, shows in comparison a lower spatial extrapolation capacity
      than the HPAI H5N1 models, with a stronger association with intensively raised
      chicken densities and anthropogenic factors.

PMID- 27885991
TI  - Retraction: MMP-13 is involved in oral cancer cell metastasis.

PMID- 27885992
TI  - Effect of accelerated aging on the cross-link density of medical grade silicones.
AB  - Four specimens of Nagor silicone of different hardness (soft, medium and hard)
      were swollen, until they reached equilibrium (i.e. constant mass) in five liquids
      at 25 degrees C, before and after accelerated aging. For the specimens swollen
      before accelerated aging, the greatest swelling was obtained in methyl
      cyclohexane, while for the specimens swollen after accelerated aging, the
      greatest swelling was obtained in cyclohexane. The cross-link density, upsilon,
      was also calculated from the swelling measurements for all the specimens, before
      and after accelerated aging, using the Flory-Rehner equation. The softer
      silicones, which swelled the most, had lower upsilon values than harder
      silicones. The amount of swelling (measured in terms of phi) and upsilon varied
      significantly (p<0.05) in some cases, between the different silicone hardness and
      between different liquids. Furthermore, the cross-link density, upsilon,
      significantly (p<0.05) increased after accelerated aging in most liquids.Note:
      phi is defined as the volume fraction of polymer in its equilibrium swollen
      state. A probability value of statistical significance of 0.05 or 5% was
      selected, hence if a p value of less than 0.05 was obtained, the null hypothesis
      was rejected (i.e. significant if p<0.05).

PMID- 27885993
TI  - Arterial pulsatility under phasic left ventricular assist device support.
AB  - The aim of this study is to understand whether the phasic Continuous Flow Left
      Ventricular Assist Device (CF-LVAD) support would increase the arterial
      pulsatility. A Micromed DeBakey CF-LVAD was used to apply phasic support in an ex
      vivo experimental platform. CF-LVAD was operated over a cardiac cycle by phase
      shifting the pulsatile pump control with respect to the heart cycle, in 0.05 s
      increments in each experiment. The pump flow rate was selected as the control
      variable and a reference model was used to operate the CF-LVAD at a pulsatile
      speed. Arterial pulse pressure was the highest (9 mmHg) when the peak pump flow
      is applied at the peak systole under varying speed CF-LVAD support over a cardiac
      cycle while it was the lowest (2 mmHg) when the peak pump flow was applied in the
      diastolic phase. The mean arterial pressure and mean CF-LVAD output were the same
      in each experiment while arterial pulse pressure and pulsatility index varied
      depending on the phase of reference pump flow rate signal. CF-LVAD speed should
      be synchronized considering the timing of peak systole over a cardiac cycle to
      increase the arterial pulsatility. Moreover, it is possible to decrease the
      arterial pulsatility under counter-pulsating CF-LVAD support.

PMID- 27885994
TI  - Plasma nitriding of titanium alloy: Effect of roughness, hardness,
      biocompatibility, and bonding with bone cement.
AB  - Titanium (Ti) alloys have been widely used in orthopedics and orthodontic
      surgeries as implants because of their beneficial chemical, mechanical, and
      biological properties. Improvement of these properties of a Ti alloy, Ti-6Al-4V
      Eli, is possible by the use of plasma nitriding treatment on the Ti alloy. The
      novelty of this study is the evaluation of a DC glow discharge nitrogen plasma
      treatment method on the surface, mechanical and biological properties of Ti
      alloy. Specifically, this study measured the chemical states, roughness,
      hardness, and biocompatibility of plasma nitride treated Ti-6Al-4V Eli as well as
      determined the effect of plasma treatment on the fracture strength between the Ti
      alloy and bone clement. This study hypothesized that DC glow discharge nitrogen
      plasma treatment may alter the surface chemical and mechanical states of the Ti
      alloy that may influence the fracture strength of implant/cement interfaces under
      static load. This study found that plasma nitride treatment on Ti alloy does not
      have effect on the roughness and biocompatibility (P value > 0.5), but
      significantly effect on the hardness and fracture strength of Ti-bone cement
      interfaces compared to those values of untreated Ti samples (P value < 0.5).
      Therefore, the DC glow discharge nitrogen plasma treated Ti alloy can potentially
      be used for orthopedic applications.

PMID- 27885995
TI  - Transdermal delivery of estradiol-loaded PLGA nanoparticles using iontophoresis
      for treatment of osteoporosis.
AB  - BACKGROUND: Estradiol is one of the therapeutic agents for osteoporosis. We have
      reported transdermal permeability of estradiol-loaded nanoparticles, and
      permeability effect of estradiol was enhanced by using nanoparticle system and
      iontophoresis [Colloids and Surfaces B: Biointerfaces97 (2012), 84-89].
      OBJECTIVE: This study was conducted in vivo to evaluate therapeutic efficacy of
      the estradiol-loaded PLGA nanoparticles for osteoporosis. METHODS: Prior to the
      in vivo study, we have determined the surface charge density of the particles and
      found they have negatively charged polyelectrolyte layers on the surfaces.
      Ovariectomized female Sprague-Dawley rats were used as an animal model of
      osteoporosis. They were separated into three groups by administration route of
      estradiol-loaded PLGA nanoparticles, passive diffusion group, iontophoresis group
      and control. After treatment, we have measured bone mineral density of spine
      using an X-ray computed tomography system. RESULTS: Bone mineral density after
      iontophoresis was significantly higher than that of passive diffusion and control
      group. By usage of iontophoresis, the nanoparticles were permeated through
      follicles and migrated into capillary vessel around follicles, and the loaded
      drug reached effective blood concentration in plasma of rat. CONCLUSIONS: From
      this study, we found that the combination with charged nanoparticle system and
      iontophoresis is useful to osteoporosis treatment.

PMID- 27885996
TI  - Improvement of biological and mechanical properties of titanium surface by anodic
      oxidation.
AB  - A homogeneous and uniform array of nanotubes with a diameter of about 70 nm was
      produced on titanium (Ti) surface by anodic oxidation. The wall thickness of the
      nanotubes was around 20 nm, and the depth was about 200 nm. The biological
      properties of the anodized Ti surface were investigated by simulated body fluid
      (SBF) soaking test and in vitro cell culture test. The mechanical properties were
      evaluated by instrumented nanoindentation test and friction-wear test. The
      results showed that the anodized Ti surface can induce the formation of bone-like
      apatite after immersion in SBF for four weeks, enhance cell adhesion,
      proliferation and gene expression, it also showed decreased friction coefficient,
      similar stiffness and Young's modulus to those of the cortical bone. Based on
      these results, it can be concluded that anodic oxidation endowed the Ti surface
      with improved biological and mechanical properties, which was attributed to the
      formation of nanostructured surface.

PMID- 27885997
TI  - The enhancement of osteogenic capacity in a synthetic BMP-2 derived peptide
      coated mineralized collagen composite in the treatment of the mandibular defects.
AB  - The novel synthetic peptide P17-BMP-2 could promote cell attachment and enhance
      osteogenic capability. A composite, comprising nano-hydroxyapatite, collagen and
      poly(L-lactide) (nHAC/PLLA), was an efficient scaffold for carrier of P17-BMP-2.
      Our aim was to investigate whether nHAC/PLLA/P17-BMP-2 accelerates the
      osteogenesis as a reliable method for mandibular defect healing in this study.
      The repair capability was assessed by the gross observation, X-ray test and
      histological observation in four animal experiment groups at 2 week and 4 week
      after surgery: Group A (control), Group B (nHAC/PLLA treatment), Group C
      (nHAC/PLLA with 2 mg/g P17-BMP-2 treatment) and Group D (nHAC/PLLA with 10 mg/g
      P17-BMP-2 treatment). The Lane-Sandhu X-ray scores of the four groups were
      compared among four groups as well. The results showed that the composites
      containing the highest content of P17- BMP-2 performed best. Therefore, the
      nHAC/PLLA with P17-BMP-2 composite can accelerate the osteogenesis for mandibular
      defect healing and could be an ideal biological material as a bone graft material
      option for clinical applications.

PMID- 27885998
TI  - Bi-ventricular finite element model of right ventricle overload in the healthy
      rat heart.
AB  - BACKGROUND: The recognition of RV overpressure is critical to human life, as this
      may signify morbidity and mortality. Right ventricle (RV) dysfunction is
      understood to have an impact on the performance of the left ventricle (LV), but
      the mechanisms remain poorly understood. It is understood that ventricular
      compliance has the ability to affect cardiac performance. In this study, a bi
      ventricular model of the rat heart was used in preference to other, single
      ventricle models. Finite element analysis (FEA) of the bi-ventricular model
      provides important information on the function of the healthy heart. METHODS: The
      passive myocardium was modelled as a nearly incompressible, hyperelastic,
      transversely isotropic material using finite element (FE) methods. Bi-ventricular
      geometries of healthy rat hearts reconstructed from magnetic resonance images
      were imported in Abaqus(c). In simulating the normal passive filling of the rat
      heart, pressures of 4.8 kPa and 0.0098 kPa were applied to the inner walls of the
      LV and RV respectively. In addition, to simulate the overpressure of the RV,
      pressures of 2.4 kPa and 4.8 kPa were applied to the endocardial walls of the LV
      and RV respectively. As boundary conditions, the circumferential and longitudinal
      displacements at the base were set to zero. The radial displacements at the base
      were left free. RESULTS: The results show that the average circumferential stress
      at the mid-wall in the overloaded model increased from 2.8 kPa to 18.2 kPa. The
      average longitudinal stress increased from 1.5 kPa to 9.7 kPa. Additionally, in
      the radial direction, the average stress increased from 0.1 kPa to 0.6 kPa in the
      mid-wall. The average circumferential strain was found to be 0.138 and 0.100 on
      the endocardium of the over pressured and healthy model respectively. The average
      circumferential stress at the epicardium, mid-wall and endocardium in the case of
      a normal heart is 10 times lower than in the overloaded heart model. CONCLUSION:
      The finite analysis method is able to provide insights into the behaviour of the
      over pressured model (myocardium). In the overloaded model the high stresses and
      strains were observed on the septal wall. The bi-ventricular model was shown to
      provide useful information relating to the over pressured ventricle. The possible
      heart dysfunction may be attributable to high stress and strain in the over
      pressured heart.

PMID- 27885999
TI  - Peripheral vasomotor activity assessment using a continuous wavelet analysis on
      webcam photoplethysmographic signals.
AB  - BACKGROUND: Vasoconstriction and vasodilation phenomena reflect the relative
      changes in the vascular bed. They induce particular modifications in the pulse
      wave magnitude. Webcams correspond to remote sensors that can be employed to
      measure the pulse wave in order to compute the pulse frequency. OBJECTIVE: Record
      and analyze pulse wave signal with a low-cost webcam to extract the amplitude
      information and assess the vasomotor activity of the participant. METHODS:
      Photoplethysmographic signals obtained from a webcam are analyzed through a
      continuous wavelet transform. The performance of the proposed filtering technique
      was evaluated using approved contact probes on a set of 12 healthy subjects after
      they perform a short but intense physical exercise. During the rest period, a
      cutaneous vasodilation is observable. RESULTS: High degrees of correlation
      between the webcam and a reference sensor were obtained. CONCLUSIONS: Webcams are
      low-cost and non-contact devices that can be used to reliably estimate both heart
      rate and peripheral vasomotor activity, notably during physical exertion.

PMID- 27886000
TI  - Evaluation of corrosion resistance and surface characteristics of orthodontic
      wires immersed in different mouthwashes.
AB  - BACKGROUND: Patients use mouthwashes in addition to mechanical cleaning during
      orthodontic treatment. The effects of mouthwashes on the archwires have not been
      examined yet. OBJECTIVE: To compare the corrosion resistance of four different
      arch wires and corrosion effects of different mouthwashes to formulate a
      biocompatible and mechanically useful arch wire and mouthwash combination.
      METHODS: Each group comprised of 4 wire samples of 2 cm 0.016 * 0.022 inch. 1st
      group: ion implanted nickel titanium (INT), 2nd group: nickel titanium, without
      ion implantation (NT), 3rd group: micro layered esthetic nickel titanium (ENT),
      4th group: stainless steel (SS) wires. They were immersed inside 2 ml of
      artificial saliva solutions (AS) for the control, or AS (9%) combined with 1 of
      the 3 mouthwashes (91%) for study groups, for 24 hours. These mouthwashes were
      essential oil (EO), chlorhexidine (CHX), sodium-fluoride (NaF). An
      electrochemical analyzer was used for electrochemical impedance spectroscopy
      measurements. RESULTS: High corrosion resistance was obtained for ENT than the
      other wires. The corrosion potentials are 0.007, -0.042, 0.074 and -0.015 V
      (Ag/AgCl) for ENT, INT, SS and NT in the artificial salivary, respectively. In
      NaF containing mouthwash Rp value of ENT is significantly high in comparison to
      others. The impedance responses of all materials increased significantly in the
      presence of NaF mouthwash as well as in the CHX mouthwash. Low frequencies are
      seen at all materials in EO mouthwash. Diameters of loops are 22, 5.9, 5.9 and
      3.7 MOmega at ENT, INT, SS and NT. CONCLUSIONS: In this study, micro layered
      esthetic nickel titanium wires are found biocompatible among other wires and NaF
      and CHX mouthwashes can be recommend for their good corrosion resistance during
      fixed orthodontic therapy.

PMID- 27886002
TI  - Three-dimensional vs. two-dimensional shear-wave elastography of the testes -
      preliminary study on a healthy collective.
AB  - INTRODUCTION: Shear wave elastography (SWE) and its derivative Supersonic Shear
      Imaging (SSI) are newer techniques for the determination of tissue elasticity by
      measuring the velocity of generated shear waves (SWV), which correlates
      positively with tissue stiffness.The techniques are integrated into many modern
      ultrasound systems and have been examined in the evaluation of viscoelastic
      properties of different organ systems. Two-dimensional shear wave elastography
      (2D SWE) of the testes has been found to be a useful tool in recent studies which
      included the determination of standard values in healthy volunteers. Three
      dimensional shear wave elastography (3D SWE) is the latest development in
      elastography and is made possible by generation of a multiplanar three
      dimensional map via volumetric acquisition with a special ultrasound transducer.
      This technique allows the assessment of tissue elasticity in a three-dimensional,
      fully accessible organ map.The aim of this preliminary study was to both evaluate
      the feasibility of 3D SWE and to compare 2D and 3D SWE standard values in the
      testes of healthy subjects. MATERIAL AND METHODS: We examined the testes of
      healthy male volunteers (n = 32) with a mean age of 51.06+/-17.75 years (range 25
      77 years) by B-mode ultrasound, 2D and 3D SWE techniques in September of 2016.
      Volunteers with a history of testicular pathologies were excluded. For all
      imaging procedures the SL15-4 linear transducer (bandwidth 4-15 MHz) as well as
      the SLV16-4 volumetric probe (bandwidth 4-16 MHz) of the Aixplorer(r) ultrasound
      device (SuperSonic Imagine, Aix-en-Provence, France) were used. Seven regions of
      interest (ROI, Q-Box(r)) within the testes were evaluated for SWV using both
      procedures. SWV values were described in m/s. Results were statistically
      evaluated using univariateanalysis. RESULTS: Mean SWV values were 1.05 m/s for
      the 2D SWE and 1.12 m/s for the 3D SWE.Comparisons of local areas delivered no
      statistically significant differences (p = 0.11 to p = 0.66), except for the
      region in the central portion in the superior part of the coronal plane (p =
      0.03). Testicular volume was significanty higher by a mean of 1.72 ml when
      measured with 3D SWE (p = 0.001). CONCLUSION: 3D SWE proved to be a feasible
      diagnostic tool in the assessment of testicular tissue, providing the examiner
      with a fully accessible three-dimensional map in a multiplanar or multislice
      view. With this technique a more precise testicular imaging - especially if
      combined with the display of tissue stiffness in SWE - is available and therefore
      could improve the diagnostic work-up of scrotal masses or the routine
      investigation of infertile men. Further studies for a better understanding in the
      context of various testicular pathologies will be required.

PMID- 27886001
TI  - Strategy for the hemocompatibility testing of microparticles.
AB  - Polymer-based microparticles are applied as non-thrombogenic or thrombogenic
      materials in a wide variety of intra- or extra-corporeal medical devices. As
      demanded by the regulatory agencies, the hemocompatibility of these blood
      contacting biomaterials has to be evaluated in vitro to ensure that the particle
      systems appropriately fulfill the envisioned function without causing undesired
      events such as thrombosis or inflammation. Currently described in vitro assays
      for hemocompatibility testing of particles comprise tests with different single
      cell types (e.g. erythrocytes or leukocytes), varying concentrations/dilutions of
      the used blood cells or whole blood, which are not standardized.Here, we report
      about an in vitro dynamic test system for studying the hemocompatibility of
      polymeric microparticles utilizing fresh human whole blood from apparently
      healthy subjects, collected and processed under standardized conditions.
      Spherical poly(ether imide) microparticles with an average diameter of 140+/-30
      MUm were utilized as model systems. Reported as candidate materials for the
      removal of uremic toxins, these microparticles are anticipated to facilitate
      optimal flow conditions in a dialyzer with minimal backflow and blood cell
      damage. Pristine (PEI) and potassium hydroxide (PEI-KOH) functionalized
      microparticles exhibited similarly nanoporous surfaces (PEI: OExternal pore =
      90+/-60 nm; PEI-KOH OExternal pore = 150+/-130 nm) but varying water
      wettabilities (PEI: thetaadv = 112+/-10 degrees  PEI-KOH thetaadv = 60+/-2
      degrees ). The nanoporosity of the microparticle surfaces allows the exchange of
      toxic solutes from blood towards the interconnective pores in the particle core,
      while an immigration of the substantially larger blood cells is
      inhibited.Sterilized PEI microparticles were incorporated -air-free -in a syringe
      based test system and exposed to whole blood for 60 minutes under gentle
      agitation. Thereafter, thrombi formation on the particles surfaces were analyzed
      microscopically. In the collected whole blood the non-adherent/circulating single
      blood cells were quantified via a differentiated complete blood cell count and
      the activation of platelets (P-Selectin expression, secretion and release),
      platelet function (PFA100 closure time) as well as thrombin formation (thrombin
      antithrombin-complex) was analyzed. Free hemoglobin (HGB) levels were quantified
      as a measure of hemolysis.Microscopic evaluation revealed thrombi formation and
      particle aggregates for all tested microparticles. Reduction of circulating blood
      cells differed significantly between the particle types. Particularly, platelet
      and monocyte counts decreased up to 50% compared to the control (syringe filled
      with whole blood but without microparticles). In accordance, platelet activation,
      thrombin levels and degrees of hemolysis were clearly elevated in the particle
      loaded test systems and allowed a differentiation between the particle types.
      Increased PFA100 closure times (as activating agent a combination of collagen/ADP
      was used) indicated a similarly reduced ability of platelets to adhere and form
      stable aggregates independent from the particle type tested. This observation is
      most probably a consequence of the strong thrombus formation in the test system,
      which is associated with a reduction of the circulating blood cells.The reported
      in vitro dynamic whole blood test system allowed the sensitive analysis of the
      hemocompatibility of polymer-based microparticles and was successfully validated
      for porous PEI microparticles with different water wettabilities. Beyond the
      qualitative and quantitative analysis of cell-material interactions, the test
      also allowed the functional evaluation of platelets in whole blood.

PMID- 27886003
TI  - MRI and contrast enhanced ultrasound (CEUS) image fusion of renal lesions.
AB  - Ultrasound is a common and established imaging method for the initial
      characterization of renal lesions. The widespread used Bosniak classification (I
      IV) classifies renal lesions in five individual groups using contrast-enhanced
      computer tomography (CE-CT), magnetic resonance imaging (MRI) and/or contrast
      enhanced ultrasound (CEUS) imaging criteria. For complex pathologies, CEUS/MRI
      image fusion is a novel imaging technique for the differentiation of benign and
      malignant renal lesions. Compared to CE-CT and MRI alone, ultrasound image fusion
      offers the additional possibility of being a real-time imaging technique that can
      be used together with other cross-sectional imaging techniques.This article
      describes the newest possibilities of image fusion with CEUS and MRI in detection
      and characterization of unclear renal lesions.

PMID- 27886004
TI  - Influence of surface roughness on neural differentiation of human induced
      pluripotent stem cells.
AB  - Induced pluripotent stem cells (iPSCs) own the capacity to develop into all cell
      types of the adult body, presenting high potential in regenerative medicine.
      Regulating and controlling the differentiation of iPSCs using the surface
      topographic cues of biomaterials is a promising and safe approach to enhance
      their therapeutic efficacy. In this study, we tested the effects of surface
      roughness on differentiation of human iPSCs into neural progenitor cells and
      dopaminergic neuron cells using polystyrene with different roughness (R0: flat
      surface; R1: rough surface, Rq ~ 6 MUm; R2: rough surface, Rq ~ 38 MUm). Neural
      differentiation of human iPSCs could be influenced by surface roughness. Up
      regulated neuronal markers were found in cells on rough surface, as examined by
      real-time PCR and immunostaining. Particularly, the R1 surface significantly
      improved the neuronal marker expression, as compared to R0 and R2 surface. This
      study demonstrates the significance of surface roughness, depending on the
      roughness level, in promoting differentiation of human iPSCs towards the neuronal
      lineage. Our study suggests the potential applications of surface roughness in
      iPSCs based treatment of neural disorder diseases, and highlights the importance
      of design and development of biomaterials with effective surface structures to
      regulate stem cells.

PMID- 27886005
TI  - Compression in the treatment of chronic venous insufficiency: Efficacy depending
      on the length of the stocking.
AB  - BACKGROUND: Below knee two-component compression stockings (AD) have revealed as
      effective for compression treatment of venous leg ulcers. Upto groin, thigh
      length stocking (AG) may enhance clinical effects, however wear comfort of these
      stocking may be affected. OBJECTIVE: venous haemodynamic in relation to the
      length of compression stockings. METHODS: A two-component AD stocking (37 mmHg)
      and two thigh length stockings (AG 37, with an interface pressure of 37 mmHg; AG
      45, with an interface pressure of 45 mmHg) were tested by 16 patients with CVI.
      Leg volume changes and venous ejection fraction and venous filling index were
      measured, whilst quality of life and wear comfort were surveyed by
      questionnaires. RESULTS: Volume of both the lower limb and the thigh was reduced
      by AG stockings, whereas AD stockings reduced only the volume of the lower limb
      and increased thigh volume. Venous hemodynamic, ejection fraction and filling
      index were improved by AG and AD stockings, AG, however, was superior to AD.
      Quality of life and comfort of the stockings was assessed as good for AG 37 mmHg,
      AG 45 mmHg and AD 37 mmHg. CONCLUSIONS: Thigh length two component stockings (AG)
      were shown to be superior to below knee stocking (AD) with regard to volume
      reduction and venous hemodynamic, yet wear comfort was not impaired. These
      results imply that healing of trophic skin changes e.g. ulcers will be faster
      when thigh length two component stocking will be worn.

PMID- 27886007
TI  - Sleep-Wake Profile in Dementia with Lewy Bodies, Alzheimer's Disease, and Normal
      Aging.
AB  - BACKGROUND: Alterations of the sleep-wake cycle are common features of
      neurodegenerative dementia. OBJECTIVES: To study differences in sleep-wake
      profiles in dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and
      healthy controls. METHODS: 30 DLB and 32 AD patients, and 33 healthy elderly
      participants were studied. Patients were evaluated for global cognitive
      impairment, extrapyramidal signs, fluctuations of attention, and behavioral
      disorders. A comprehensive sleep-wake profile was obtained including a set of
      questionnaires [Pittsburgh Sleep Quality Index (PSQI), REM Sleep Behavior
      Disorder Single-Question screen (RBD1Q), Epworth Sleepiness Scale (ESS)] and 12
      day sleep diaries. RESULTS: Patients were matched for age, gender, and disease
      severity. DLB patients showed more severe daytime somnolence/dysfunction due to
      somnolence, and a higher proportion of RBD-like symptoms (70%) compared to AD and
      controls (p < 0.001), regardless of the presence of psychoactive drug treatment.
      As for sleep timing, DLB patients had a greater number of daytime naps and longer
      night sleep, with the latter being associated with use of clonazepam. The
      severity of fluctuations was associated with the presence of RBD (Clinician
      Assessment of Fluctuation score = RBD+: 5.2+/-3.7; RBD-: 2.1+/-3.2, p = 0.04). AD
      patients reported the best sleep-wake profile, while healthy controls declared
      the poorest sleep quality, although sleep timing and the quality of wakefulness
      were comparable between AD and controls. DISCUSSION: RBD and daytime fluctuations
      of attention may coexist in DLB and even reciprocally potentiate each other. Self
      reports of sleep quality may lead to an underestimation of sleep disturbances in
      AD, possibly influenced by anosognosia, compared to normal elderly individuals
      who complain mainly of insomnia.

PMID- 27886006
TI  - Semi-automated extraction and characterization of Stromal Vascular Fraction using
      a new medical device.
AB  - INTRODUCTION: The stem cell rich Stromal Vascular Fraction (SVF) can be harvested
      by processing lipo-aspirate or fat tissue with an enzymatic digestion followed by
      centrifugation. To date neither a standardised extraction method for SVF nor a
      generally admitted protocol for cell application in patients exists. A novel
      commercially available semi-automated device for the extraction of SVF promises
      sterility, consistent results and usability in the clinical routine. The aim of
      this work was to compare the quantity and quality of the SVF between the new
      system and an established manual laboratory method. MATERIAL AND METHODS: SVF was
      extracted from lipo-aspirate both by a prototype of the semi-automated
      UNiStationTM (NeoGenesis, Seoul, Korea) and by hand preparation with common
      laboratory equipment. Cell composition of the SVF was characterized by multi
      parametric flow-cytometry (FACSCanto-II, BD Biosciences). The total cell number
      (quantity) of the SVF was determined as well the percentage of cells expressing
      the stem cell marker CD34, the leucocyte marker CD45 and the marker CD271 for
      highly proliferative stem cells (quality). RESULTS: Lipo-aspirate obtained from
      six patients was processed with both the novel device (d) and the hand
      preparation (h) which always resulted in a macroscopically visible SVF. However,
      there was a tendency of a fewer cell yield per gram of used lipo-aspirate with
      the device (d: 1.1*105+/-1.1*105 vs. h: 2.0*105+/-1.7*105; p = 0.06). Noteworthy,
      the percentage of CD34+ cells was significantly lower when using the device (d:
      57.3% +/-23.8% vs. h: 74.1% +/-13.4%; p = 0.02) and CD45+ leukocyte counts tend
      to be higher when compared to the hand preparation (d: 20.7% +/-15.8% vs. h: 9.8%
      +/-7.1%; p = 0.07). The percentage of highly proliferative CD271+ cells was
      similar for both methods (d:12.9% +/-9.6% vs. h: 13.4% +/-11.6%; p = 0.74) and no
      differences were found for double positive cells of CD34+/CD45+ (d: 5.9% +/-1.7%
      vs. h: 1.7% +/-1.1%; p = 0.13), CD34+/CD271+ (d: 24.1% +/-12.0% vs. h: 14.2% +/
      8.5%; p = 0.07). DISCUSSION: The semi-automated closed system provides a
      considerable amount of sterile SVF with high reproducibility. Furthermore, the
      SVF extracted by both methods showed a similar cell composition which is in
      accordance with the data from literature. This semi-automated device offers an
      opportunity to take research and application of the SVF one step further to the
      clinic.

PMID- 27886008
TI  - The Alteration of ZiBuPiYin Recipe on Proteomic Profiling of Forebrain
      Postsynaptic Density of db/db Mice with Diabetes-Associated Cognitive Decline.
AB  - Diabetes-associated cognitive decline (DACD) is a brain injury induced by
      diabetes mellitus, with cognitive impairment as the major symptom. Growing
      evidence has revealed that DACD is correlated with disruptions in synapses
      involved in cognition. Within synapses, more specifically in areas of
      postsynaptic density (PSD), there is a high concentration of proteins that
      receive and transduce synaptic information. In the present study, to identify the
      differentially expressed PSD proteins among DACD mice, ZiBuPiYin recipe (ZBPYR)
      treated DACD mice and control mice, we applied isobaric tags for relative and
      absolute quantitation (iTRAQ) with LC-MS/MS technology, by which three biological
      replicates and three technical replicates were examined. A total of 24 and 23
      differentially expressed proteins were observed in control versus DACD mice and
      in DACD versus ZBPYR-treated DACD mice, respectively. Notably, we found 'Protein
      processing in endoplasmic reticulum' and 'PI3K-Akt signaling pathway' might be
      impaired in DACD pathogenesis, while Growth factor receptor-bound protein 2 might
      be a crucial protein as a molecular target of the neuroprotective effects of
      ZBPYR. To our knowledge, this is the first study to provide a reference proteome
      map for DACD and ZBPYR-treated DACD mouse forebrain PSD to aid understanding the
      underlying mechanisms of DACD and ZBPYR.

PMID- 27886009
TI  - Diagnostic Accuracy of a Combined Analysis of Cerebrospinal Fluid t-PrP, t-tau, p
      tau, and Abeta42 in the Differential Diagnosis of Creutzfeldt-Jakob Disease from
      Alzheimer's Disease with Emphasis on Atypical Disease Variants.
AB  - According to recent studies, the determination of cerebrospinal fluid (CSF) total
      tau (t-tau)/phosphorylated tau (p-tau) ratio and total prion protein (t-PrP)
      levels significantly improves the accuracy of the diagnosis of Alzheimer's
      disease (AD) in atypical cases with clinical or laboratory features mimicking
      Creutzfeldt-Jakob disease (CJD). However, this has neither been validated nor
      tested in series including atypical CJD variants. Furthermore, the added
      diagnostic value of amyloid-beta (Abeta)42 remains unclear. To address these
      issues, we measured t-PrP, 14-3-3, t-tau, p-tau, and Abeta42 CSF levels in 45
      typical and 44 atypical/rapidly progressive AD patients, 54 typical and 54
      atypical CJD patients, and 33 controls. CJD patients showed significantly lower
      CSF t-PrP levels than controls and AD patients. Furthermore, atypical CJD was
      associated with lower t-PrP levels in comparison to typical CJD. T-tau, 14-3-3,
      or t-PrP alone yielded, respectively, 80.6, 63.0, and 73.0% sensitivity and 75.3,
      92.1, and 75% specificity in distinguishing AD from CJD. On receiver operating
      characteristic (ROC) curve analyses of biomarker combinations, the (t
      tau*Abeta42)/(p-tau*t-PrP) ratio achieved the best accuracy, with 98.1%
      sensitivity and 97.7% specificity overall, and 96.2% sensitivity and 95.5%
      specificity for the "atypical" disease groups. Our results show that the combined
      analysis of CSF t-PrP, t-tau, p-tau, and Abeta42 is clinically useful in the
      differential diagnosis between CJD and AD. Furthermore, the finding of reduced
      CSF t-PrP levels in CJD patients suggest that, likewise Abeta42 in AD, CSF t-PrP
      levels reflect the extent of PrPc conversion into abnormal PrP (PrPSc) and the
      burden of PrPSc deposition in CJD.

PMID- 27886010
TI  - Discriminative Properties of Hippocampal Hypoperfusion in Marijuana Users
      Compared to Healthy Controls: Implications for Marijuana Administration in
      Alzheimer's Dementia.
AB  - BACKGROUND: Few studies have evaluated the impact of marijuana use on regional
      cerebral blood flow. OBJECTIVE: To determine whether perfusion in specific brain
      regions on functional neuroimaging, including those affected by Alzheimer's
      disease pathology, are abnormal in marijuana users compared to controls. METHOD:
      Persons with a diagnosis of cannabis use disorder by DSM-IV and DSM-V criteria (n
      = 982) were compared to controls (n = 92) with perfusion neuroimaging with SPECT
      at rest and at a concentration task. Perfusion estimates were quantified using a
      standard atlas. Cerebral perfusion differences were calculated using one-way
      ANOVA. Diagnostic separation was determined with discriminant analysis of all
      subjects. Feature selection with a minimum redundancy maximum relevancy (mRMR)
      identified predictive regions in a subset of marijuana users (n = 436) with
      reduced psychiatric co-morbidities. RESULTS: Marijuana users showed lower
      cerebral perfusion on average (p < 0.05). Discriminant analysis distinguished
      marijuana users from controls with correct classification of 96% and leave one
      out cross-validation of 92%. With concentration SPECT regions, there was correct
      classification of 95% with a leave-one-out cross validation of 90%. AUC analysis
      for concentration SPECT regions showed 95% accuracy, 90% sensitivity, and 83%
      specificity. The mRMR analysis showed right hippocampal hypoperfusion on
      concentration SPECT imaging was the most predictive in separating marijuana
      subjects from controls. CONCLUSION: Multiple brain regions show low perfusion on
      SPECT in marijuana users. The most predictive region distinguishing marijuana
      users from healthy controls, the hippocampus, is a key target of Alzheimer's
      disease pathology. This study raises the possibility of deleterious brain effects
      of marijuana use.

PMID- 27886012
TI  - Histogram-Based Feature Extraction from Individual Gray Matter Similarity-Matrix
      for Alzheimer's Disease Classification.
AB  - Automatic computer-aided diagnosis (CAD) systems have been widely used in
      classification of patients who suffer from Alzheimer's disease (AD). This paper
      presents an automatic CAD system based on histogram feature extraction from
      single-subject gray matter similarity-matrix for classifying the AD patients from
      healthy controls (HC) using structural magnetic resonance imaging (MRI) data. The
      proposed CAD system is composed of five stages. In the first stage, segmentation
      is employed to perform pre-processing on the MRI images, and segment into gray
      matter, white matter, and cerebrospinal fluid using the voxel-based morphometric
      toolbox procedure. In the second stage, gray matter MRI scans are used to
      construct similarity-matrices. In the third stage, a novel statistical feature
      generation process is proposed, utilizing the histogram of the individual
      similarity-matrix to represent statistical patterns of the respective similarity
      matrices of different size and order into fixed-size feature-vectors. In the
      fourth stage, we propose to combine MRI measures with a neuropsychological test,
      the Functional Assessment Questionnaire (FAQ), to improve the classification
      accuracy. Finally, the classification is performed using a support vector machine
      and evaluated with the 10-fold cross-validation strategy. We evaluated the
      proposed method on 99 AD and 102 HC subjects from the J-ADNI. The proposed CAD
      system yields an 84.07% classification accuracy using MRI measures and 97.01% for
      combining MRI measures with FAQ scores, respectively. The experimental results
      indicate that the performance of the proposed system is competitive with respect
      to state-of-the-art techniques reported in the literature.

PMID- 27886011
TI  - Odor Identification Screening Improves Diagnostic Classification in Incipient
      Alzheimer's Disease.
AB  - BACKGROUND: Measurements of olfaction may serve as useful biomarkers of incipient
      dementia. Here we examine the improvement in diagnostic accuracy of Alzheimer's
      disease (AD) and mild cognitive impairment (MCI) when assessing both cognitive
      functioning and odor identification. OBJECTIVE: To determine the utility of odor
      identification as a supplementary screening test in incipient AD. METHODS:
      Sniffin' Sticks Odor Identification Test (SS-OIT) and the Montreal Cognitive
      Assessment (MoCA) were administered in 262 AD, 174 MCI [150 amnestic (aMCI), and
      24 non-amnestic (naMCI)], and 292 healthy older adults (HOA). RESULTS: Odor
      identification scores were higher in HOA relative to MCI or AD groups, and MCI
      outperformed AD. Odor identification scores were higher in aMCI single domain
      than aMCI multiple domain. Complementing MoCA scores with the SS-OIT
      significantly improved diagnostic accuracy of individuals with AD and MCI,
      including within MCI subgroups. DISCUSSION: Odor identification is a useful
      supplementary screening tool that provides additional information relevant for
      clinical categorization of AD and MCI, including those who are at highest risk to
      convert to AD.

PMID- 27886013
TI  - Is Salivary Chromogranin A a Valid Psychological Stress Biomarker During Sensory
      Stimulation in People with Advanced Dementia?
AB  - Salivary chromogranin A (sCgA) is gaining attention as a biomarker of
      psychological stress. The objective of this work was to determine whether
      individualized music intervention and multisensory stimulation environment (MSSE)
      in a Snoezelen room produce changes in sCgA in severely demented older patients,
      and to assess the possible existence of differences in sCgA levels between the
      two types of interventions. Older adults with severe dementia (n = 22) were
      randomly assigned to two intervention groups. They participated in MSSE or
      individualized music interventions in 30-min weekly sessions for 16 weeks. Levels
      of sCgA were evaluated before and after a session, or 30-min interval, at four
      different time points: before starting the trial, in the middle and end of the
      intervention period, and two months later. Comparison of sCgA values obtained
      after each session with those obtained before (or at the same hour in before
      trial and follow-up samplings) showed no significant differences either in the
      individualized music or in the MSSE group at any sampling time. Comparison
      between the two types of interventions, both before and after each session, in
      the four sampling times, did not produce any significant difference either.
      Furthermore, no significant correlation was obtained between agitation, anxiety,
      cognitive function, and dementia severity with sCgA levels. In conclusion,
      despite beneficial effects of both individualized music and MSSE interventions
      being previously reported on neuropsychiatric outcomes for older patients with
      dementia, sCgA seems to not be a good indicator of these benefits.

PMID- 27886014
TI  - Embryonic Mutant Huntingtin Aggregate Formation in Mouse Models of Huntington's
      Disease.
AB  - The role of aggregate formation in the pathophysiology of Huntington's disease
      (HD) remains uncertain. However, the temporal appearance of aggregates tends to
      correlate with the onset of symptoms and the numbers of neuropil aggregates
      correlate with the progression of clinical disease. Using highly sensitive
      immunohistochemical methods we have detected the appearance of diffuse aggregates
      during embryonic development in the R6/2 and YAC128 mouse models of HD. These are
      initially seen in developing axonal tracts and appear to spread throughout the
      cerebrum in the early neonate.

PMID- 27886016
TI  - An Internet of Things platform architecture for supporting ambient assisted
      living environments.
AB  - Internet of Things (IoT) is the logical further development of today's Internet,
      enabling a huge amount of devices to communicate, compute, sense and act. IoT
      sensors placed in Ambient Assisted Living (AAL) environments, enable the context
      awareness and allow the support of the elderly in their daily routines,
      ultimately allowing an independent and safe lifestyle. The vast amount of data
      that are generated and exchanged between the IoT nodes require innovative context
      modeling approaches that go beyond currently used models. Current paper presents
      and evaluates an open interoperable platform architecture in order to utilize the
      technical characteristics of IoT and handle the large amount of generated data,
      as a solution to the technical requirements of AAL applications.

PMID- 27886017
TI  - Influence of proprioceptive insoles on spinal curvature in patients with slight
      idiopathic scoliosis.
AB  - PURPOSE: Proprioceptive insoles are known to influence the functions of posture
      and gait by modulations of the sensory structures at the sole of the foot.
      Literature has shown that they could improve the position of the upper-body in
      patients with postural complaints of the musculoskeletal system. The aim of this
      study was to evaluate the influence of proprioceptive insoles on the spinal
      curvature in patients with slight idiopathic scoliosis. PATIENTS AND METHODS:
      Eighteen patients were included in this prospective, single-centre, randomized
      study. All patients needed to have a relevant growth potential and suffered from
      a slight idiopathic scoliosis. Two groups were used, where group 1 performed
      physiotherapy twice a week, whereas group 2 was additionally supplied with
      proprioceptive insoles. Patients underwent three-dimensional rasterstereography
      for back-shape analysis. Furthermore, a conventional x-ray imaging of the spine
      was performed at the beginning and 1 year later to document the curvatures.
      RESULTS: There was no statistical difference in the Cobb angles, and in almost
      all parameters of the rasterstereography, there was no statistically significant
      change between and within both groups. CONCLUSION: According to the results of
      this study, there was no evidence of any statistical significant effect of
      proprioceptive insoles on spinal curvature in patients with slight idiopathic
      scoliosis.

PMID- 27886019
TI  - An analysis of a digital variant of the Trail Making Test using machine learning
      techniques.
AB  - BACKGROUND: The goal of this work is to develop a digital version of a standard
      cognitive assessment, the Trail Making Test (TMT), and assess its utility.
      OBJECTIVE: This paper introduces a novel digital version of the TMT and
      introduces a machine learning based approach to assess its capabilities. METHODS:
      Using digital Trail Making Test (dTMT) data collected from (N = 54) older adult
      participants as feature sets, we use machine learning techniques to analyze the
      utility of the dTMT and evaluate the insights provided by the digital features.
      RESULTS: Predicted TMT scores correlate well with clinical digital test scores (r
      = 0.98) and paper time to completion scores (r = 0.65). Predicted TICS exhibited
      a small correlation with clinically derived TICS scores (r = 0.12 Part A, r =
      0.10 Part B). Predicted FAB scores exhibited a small correlation with clinically
      derived FAB scores (r = 0.13 Part A, r = 0.29 for Part B). Digitally derived
      features were also used to predict diagnosis (AUC of 0.65). CONCLUSION: Our
      findings indicate that the dTMT is capable of measuring the same aspects of
      cognition as the paper-based TMT. Furthermore, the dTMT's additional data may be
      able to help monitor other cognitive processes not captured by the paper-based
      TMT alone.

PMID- 27886018
TI  - Radiofrequency-activated PMMA-augmentation through cannulated pedicle screws: A
      cadaver study to determine the biomechanical benefits in the osteoporotic spine.
AB  - INTRODUCTION: PMMA-augmentation of pedicle screws strengthens the bone-screw
      interface reducing cut-out risk. Injection of fluid cement bears a higher risk of
      extravasation, with difficulty of application because of inconsistent viscosity
      and limited injection time. OBJECTIVE: To test a new method of cement
      augmentation of pedicle screws using radiofrequency-activated PMMA, which is
      suspected to be easier to apply and have less extravasations. METHODS: Twenty
      seven fresh-frozen human cadaver lumbar spines were divided into 18 osteoporotic
      (BMD <= 0.8 g/cm2) and 9 non-osteoporotic (BMD > 0.8 g/cm2) vertebral bodies.
      Bipedicular cannulated pedicle screws were implanted into the vertebral bodies;
      right screws were augmented with ultra-high viscosity PMMA, whereas un-cemented
      left pedicle screws served as negative controls. Cement distribution was
      controlled with fluoroscopy and CT scans. Axial pullout forces of the screws were
      measured with a material testing machine, and results were analyzed
      statistically. RESULTS: Fluoroscopy and CT scans showed that in all cases an
      adequately big cement depot with homogenous form and no signs of extravasation
      was injected. Pullout forces showed significant differences (p < 0.001) between
      the augmented and non-augmented pedicle screws for bone densities below 0.8 g/cm2
      (661.9 N +/- 439) and over 0.8 g/cm2 (744.9 N +/- 415). CONCLUSIONS: Pullout
      forces were significantly increased in osteoporotic as well as in non
      osteoporotic vertebral bodies without a significant difference between these
      groups using this standardized, simple procedure with increased control and less
      complications like extravasation.

PMID- 27886020
TI  - Cranial electrotherapy stimulation affects mood state but not levels of
      peripheral neurotrophic factors or hypothalamic- pituitary-adrenal axis
      regulation.
AB  - Cranial electrotherapy stimulation (CES) is reported to aid in relieving symptoms
      of depression and anxiety, though the mechanism underlying this effect remains
      unclear. Therefore, the present study aimed to evaluate changes in the
      hypothalamic-pituitary-adrenal (HPA) axis response and levels of neurotrophic
      factors, as well as changes in mood state, in patients undergoing CES therapy.
      Fifty healthy postmenopausal women were randomly assigned to either a Sham CES
      group (n = 25) or an Active CES group (n = 25). CES treatment was conducted in 20
      minute sessions, three times per week for 8 weeks, using a micro current cranial
      electrotherapy stimulator. Blood samples were collected prior to and following
      the 8-week treatment period for measurement of cortisol, adrenocorticotropic
      hormone (ACTH), brain-derived neurotrophic factor (BDNF), and nerve growth factor
      (NGF) levels. Changes in mood state were also examined at the time of blood
      collection using the Profile of Mood States (POMS). No significant differences in
      cortisol, ACTH, BDNF, or NGF were observed between the two participant groups (p
      > 0.05) following the treatment period. However, those in the Active CES group
      exhibited significantly decreased Tension-Anxiety and Depression-Dejection scores
      on the POMS relative to pre-treatment scores (p < 0.05). Furthermore, Depression
      Dejection scores following treatment were significantly lower in the Active CES
      group than in the Sham CES group (p < 0.05). No significant differences were
      observed in any other POMS scores such as Anger-Hostility, Vigor-Activity,
      Fatigue-Inertia, and Confusion-Bewilderment (p > 0.05). These results suggest
      that 8 weeks of CES treatment does not induce changes in blood levels of
      neurotrophic factors or HPA-axis-related hormones, though such treatment may be
      effective in treating symptoms of anxiety and depression.

PMID- 27886021
TI  - Revision of orthovoltage chest wall treatment using Monte Carlo simulations.
AB  - PURPOSE: Given the high local control rates observed in breast cancer patients
      undergoing chest wall irradiation by kilovoltage x-rays, we aimed to revisit this
      treatment modality by accurate calculation of dose distributions using Monte
      Carlo simulation. METHODS AND MATERIAL: The machine components were simulated
      using the MCNPX code. This model was used to assess the dose distribution of
      chest wall kilovoltage treatment in different chest wall thicknesses and larger
      contour or fat patients in standard and mid sternum treatment plans. Assessments
      were performed at 50 and 100 cm focus surface distance (FSD) and different
      irradiation angles. In order to evaluate different plans, indices like
      homogeneity index, conformity index, the average dose of heart, lung, left
      anterior descending artery (LAD) and percentage target coverage (PTC) were used.
      Finally, the results were compared with the indices provided by electron therapy
      which is a more routine treatment of chest wall. RESULT: These indices in a
      medium chest wall thickness in standard treatment plan at 50 cm FSD and 15
      degrees tube angle was as follows: homogeneity index 2.57, conformity index 7.31,
      average target dose 27.43 Gy, average dose of heart, lung and LAD, 1.03, 2.08 and
      1.60 Gy respectively and PTC 11.19%. Assessments revealed that dose homogeneity
      in planning target volume (PTV) and conformity between the high dose region and
      PTV was poor. To improve the treatment indices, the reference point was
      transferred from the chest wall skin surface to the center of PTV. The indices
      changed as follows: conformity index 7.31, average target dose 60.19 Gy, the
      average dose of heart, lung and LAD, 3.57, 6.38 and 5.05 Gy respectively and PTC
      55.24%. Coverage index of electron therapy was 89% while it was 22.74% in the old
      orthovoltage method and also the average dose of the target was about 50 Gy but
      in the given method it was almost 30 Gy. CONCLUSION: The results of the treatment
      study show that the optimized standard and mid sternum treatment for different
      chest wall thicknesses is with 50 cm FSD and zero (vertical) tube angle, while in
      large contour patients, it is with 100 cm FSD and zero tube angle. Finally, chest
      wall kilovoltage and electron therapies were compared, which revealed that
      electron therapy produces a better dose distribution than kilovoltage therapy.

PMID- 27886023
TI  - Quantifying the dynamic of OSA brain using multifractal formalism: A novel
      measure for sleep fragmentation.
AB  - It is thought that the critical brain dynamics in sleep is modulated during
      frequent periods of wakefulness. This paper utilizes the capacity of EEG based
      scaling analysis to quantify sleep fragmentation in patients with obstructive
      sleep apnea. The scale-free (fractal) behavior refers to a state where no
      characteristic scale dominates the dynamics of the underlying process which is
      evident as long range correlations in a time series. Here, Multiscaling
      (multifractal) spectrum is utilized to quantify the disturbed dynamic of an OSA
      brain with fragmented sleep. The whole night multichannel sleep EEG recordings of
      18 subjects were employed to compute and quantify variable power-law long-range
      correlations and singularity spectra. Based on this characteristic, a new marker
      for sleep fragmentation named ''scaling based sleep fragmentation'' was
      introduced. This measure takes into account the sleep run length and stage
      transition quality within a fuzzy inference system to improve decisions made on
      sleep fragmentation. The proposed index was implemented, validated with
      sleepiness parameters and compared to some common indexes including sleep
      fragmentation index, arousal index, sleep diversity index, and sleep efficiency
      index. Correlations were almost significant suggesting that the sleep
      characterizing measure, based on singularity spectra range, could properly detect
      fragmentations and quantify their rate. This method can be an alternative for
      quantifying the sleep fragmentation in clinical practice after being approved
      experimentally. Control of sleep fragmentation and, subsequently, suppression of
      excessive daytime sleepiness will be a promising outlook of this kind of
      researches.

PMID- 27886022
TI  - Fracture risk of vertebral bodies after cryosurgery using a miniature cryoprobe:
      A biomechanical in-vitro analysis on human bones.
AB  - INTRODUCTION: Due to spinal instability and compressive neurologic deficits
      surgical management is sometimes necessary in patients with metastatic spinal
      lesions. However, in some cases open surgery is not possible and minimally
      invasive procedures, like cryoablation, are needed. The aim of the current study
      was to investigate whether a miniature cryoprobe provides adequate tissue cooling
      in vertebrae and to evaluate the direct impact of cryosurgery on vertebral body
      stability. MATERIALS AND METHODS: Twelve thoracic vertebral bodies were harvested
      from fresh cadavers. After documenting bone density cryoablation was performed in
      six vertebral bodies according to a standardized procedure. Afterwards
      temperature inside the vertebral body and maximum breaking force were measured in
      the control and experimental groups. RESULTS: Required temperature of -50 degrees
      was reached in all areas. There was a significant correlation between maximum
      breaking force and measured bone density (p= 0.001). Mean breaking force within
      the experimental group was 5047 N (SD = 2955 N) compared to 4458 N (SD = 2554 N)
      in the control group. There were no observable differences in maximum breaking
      force between both groups. CONCLUSION: Miniature cryoprobe can deliver adequate
      tissue cooling to -50 degrees C in vertebral bodies. The procedure does not seem
      to influence breaking force of the treated bones in-vitro. Therefore, using
      miniature probes cryosurgery may provide a valuable alternative to conventional
      surgical resection of neoplastic diseases as well as of benign locally aggressive
      bone tumors.

PMID- 27886026
TI  - Keyword Index Volume 24 (2016).

PMID- 27886024
TI  - Predicting adherence to use of remote health monitoring systems in a cohort of
      patients with chronic heart failure.
AB  - BACKGROUND: It is unclear whether subgroups of patients may benefit from remote
      monitoring systems (RMS) and what user characteristics and contextual factors
      determine effective use of RMS in patients with heart failure (HF). OBJECTIVE:
      The study was conducted to determine whether certain user characteristics (i.e.
      personal and clinical variables) predict use of RMS using advanced machine
      learning software algorithms in patients with HF. METHODS: This pilot study was a
      single-arm experimental study with a pre- (baseline) and post- (3 months) design;
      data from the baseline measures were used for the current data analyses. Sixteen
      patients provided consent; only 7 patients (mean age 65.8 +/- 6.1, range 58-83)
      accessed the RMS and transmitted daily data (e.g. weight, blood pressure) as
      instructed during the 12 week study duration. RESULTS: Baseline demographic and
      clinical characteristics of users and non-users were comparable for a majority of
      factors. However, users were more likely to have no HF specialty based care or an
      automatic internal cardioverter defibrillator. The precision accuracy of decision
      tree, multilayer perceptron (MLP) and k-Nearest Neighbor (k-NN) classifiers for
      predicting access to RMS was 87.5%, 90.3%, and 94.5% respectively. CONCLUSION:
      Our preliminary data show that a small set of baseline attributes is sufficient
      to predict subgroups of patients who had a higher likelihood of using RMS. While
      our findings shed light on potential end-users more likely to benefit from RMS
      based interventions, additional research in a larger sample is warranted to
      explicate the impact of user characteristics on actual use of these technologies.

PMID- 27886027
TI  - Epidemiology of hepatitis C in the Republic of Moldova: achievements and
      remaining challenges in prevention and control.
AB  - Viral hepatitis, especially those with parenteral and sexual transmission, still
      remain a major problem of public health, both globally and for the Republic of
      Moldova, due to wide spreading, endemicity, increased morbidity and mortality and
      high rate of invalidity following the chronization of infection, but usually
      neglected by population and public health authorities. This paper describes the
      epidemiology and preventive and control measures of hepatitis C in Moldova.
      Epidemiological analysis of the surveillance data on hepatitis C incidence in the
      Republic of Moldova was conducted. The data were obtained from the national
      reporting system of infectious diseases and serosurvey studies. Epidemiological
      particularities of acute and chronic hepatitis C in general Moldovan population
      and specific risk groups were evaluated. National hepatitis policies for
      prevention and control were analyzed. Only consolidation of all the actions
      stipulated in the national and international normative documents on the
      prevention and control of hepatitis, will help to reduce the morbidity of viral
      hepatitis C and probably to eliminate the new cases of disease in some regions.

PMID- 27886028
TI  - Salmonella serovars along two beef chains in Ethiopia.
AB  - INTRODUCTION: Salmonella has been reported from foods and the food production
      environment, with outbreaks occurring in the human population worldwide.
      METHODOLOGY: A survey on Salmonella in two beef production lines (a beef abattoir
      line and a processing line) in Addis Ababa, Ethiopia was conducted, with a total
      of 668 various samples randomly collected from animal-related materials, the
      environment, and a beef product (mortadella). RESULTS: Overall, a 12.9%
      prevalence (26.3% from the abattoir line, 5.3% from the processing plant line)
      was observed. The prevalence in the abattoir line environment (36.6%) was higher
      than that in animal-related samples (14.7%); the reverse was true for the
      processing plant line. Out of 86 isolates, 10 serovars were identified, and 8
      remained unidentified. The predominant serotypes were S. Saintpaul (32.5%), S.
      Muenchen (19.8%), and S. Larochelle (12.8%). S. Kastrup and S. London were
      isolated for the first time in Ethiopia. CONCLUSIONS: Data indicate open ports of
      entry for Salmonella, with possible transfer along the line. Further
      investigations from farm to fork are recommended in order to identify these
      positions of entry.

PMID- 27886029
TI  - Prevalence of H. pylori in gastric biopsy specimen in the southeastern region of
      Turkey.
AB  - INTRODUCTION: Helicobacter pylori is a Gram-negative, microaerophilic bacterium
      that colonizes human gastric mucosa. Gastric ulcer, duodenal ulcer, chronic
      atrophic gastritis, mucosa-associated lymphoid tissue lymphoma, and stomach
      adenocarcinoma are associated with H. pylori as the etiological agent. Cytotoxin
      associated gene A (cagA), which is one of the most important virulence factors of
      H. pylori, encodes a 120-145 kDa protein. The prevalence of cagA genes shows
      differences in H. pylori infections based on geographical area, and cagA-positive
      H. pylori strains play an important role in pathogenesis of gastric carcinoma.
      METHODOLOGY: The aim of this study was to detect the prevalence of cagA and vacA
      genes in H. pylori isolates in adult patient groups in the southeastern region of
      Turkey. The presence of H. pylori was investigated in gastric biopsy specimens
      using the culture method, and polymerase chain reaction (PCR) analysis was
      performed to detect the presence of the cagA and vacA s1 genes. RESULTS: H.
      pylori was detected in 65% (84/129) of patients who had gastrointestinal
      complaints. The number of vacA s1 and cagA genes of isolates were 44 (74.5%) and
      31 (52.5%), respectively. CONCLUSIONS: H. pylori infection in southeastern region
      of Turkey with are comparable to those in developed countries. Patients with cagA
      and vacA-positive H. pylori have a higher risk of severe inflammation and
      atrophy and should therefore be monitored for the development of gastric cancer.

PMID- 27886030
TI  - Effect of human development index parameters on tuberculosis incidence in Turkish
      provinces.
AB  - INTRODUCTION: A country's development level is measured with a quantitative
      parameter called the human development index (HDI). The present study researched
      the effects of HDI parameters (such as healthcare standards, income, and
      education level) on the incidence of tuberculosis. METHODOLOGY: HDI data of 36
      provinces of Turkey and the tuberculosis surveillance data were obtained from the
      Ministry of Development and the Ministry of Health, respectively. The
      associations between the incidence of tuberculosis and other HDI parameters were
      analyzed. RESULTS: Higher population density (n/km2) (CI = 0.05 to 0.40) and
      higher relapse rate of tuberculosis (CI = 0.36 to 1.48) were identified to be
      independent predicting factors that increased the incidence of tuberculosis,
      whereas higher gross national product (CI = -0.06 to 0.00), the population that
      holds a green Medicare card (CI=-0.58 to -0.04), increased general practitioners
      per 100,000 people (CI=-0.66 to -0.01), female population (CI = -0.70 to -0.06),
      married population (CI = -1.34 to -0.03), were found to be significant negative
      predicting factors that were relevant to the incidence (protective against
      tuberculosis). CONCLUSIONS: Tuberculosis is a disease that is affected by
      multiple factors, including the components of HDI. Improvement of income level,
      facilitation of access to health services via health insurance, urbanization with
      lower population density strategy, and provision of enough general practitioners
      may be useful in reducing the incidence of TB' in provinces of developing
      countries such as Turkey.

PMID- 27886031
TI  - Pertussis in north-central and northwestern regions of Algeria.
AB  - INTRODUCTION: Pertussis outbreaks continue to occur in many countries despite
      high vaccination coverage. Under-diagnosed cases in adolescents and adults may
      result in increased transmission to infants, who are at risk of severe pertussis.
      Additional measures to protect both groups should be considered. METHODOLOGY:
      Nasopharyngeal samples and sera were collected from patients and household
      contacts with clinically suspected pertussis. Diagnoses were confirmed by
      culture, real-time polymerase chain reaction (PCR), and serology. Bordetella
      pertussis isolates were characterized by antimicrobial sensitivity and fimbrial
      serotyping. RESULTS: Of 392 participants, 134/248 patients (54%) and 66/144
      contacts (45.8%) had confirmed pertussis infections. B. parapertussis was not
      detected. All B. pertussis isolates were sensitive to the antibiotics tested, and
      all expressed the Fim3, not the Fim2, fimbrial serotype. Most patients (81.2%)
      were <6 months (51.8% of whom were <3 months) of age; 77.6% were unvaccinated,
      and most positive contacts were mothers 20-40 years of age. CONCLUSIONS: Despite
      high vaccination coverage, pertussis is circulating in Algeria. Most infections
      occur in unvaccinated infants <6 months of age, with mothers as the main source
      of infection. An adolescent/adult booster should be considered. Adoption of
      sensitive and specific laboratory tests would improve pertussis diagnosis and
      surveillance.

PMID- 27886032
TI  - Prevalence and factors associated with different pathogens of acute diarrhea in
      adults in Beijing, China.
AB  - INTRODUCTION: Only a small proportion of patients with diarrhea are diagnosed
      with laboratory tests in China, and most are diagnosed based on clinical
      symptoms. Therefore, understanding the prevalence of different diarrheal
      pathogens and their specific symptoms is important. METHODOLOGY: Data from a
      prospective study in Beijing of acute diarrhea and the related pathogens were
      used to study the association between different pathogen groups and the infected
      patients' characteristics. A total of 355 patients with acute diarrhea,
      clinically diagnosed with infectious or noninfectious diarrhea by general
      practitioners (GPs), were recruited from three districts. RESULTS: Different
      species of diarrheal pathogens were detected in 133 (37.5%) patients. The most
      prevalent pathogen was calicivirus (42.9%), followed by rotavirus (30.1%), Vibrio
      parahaemolyticus (13.5%), and Salmonella spp. (10.5%). The detection rates in
      patients diagnosed with infectious or noninfectious diarrhea by GPs did not
      differ significantly (c2 = 0.026, p = 0.873). Abdominal pain correlated
      negatively with viral pathogens, whereas nausea, living in the suburbs, and
      winter infection correlated positively with viral infection. Abdominal pain and
      leukocytosis were positively associated with bacterial infections, whereas winter
      infection correlated negatively with them. CONCLUSION: In this study, we found
      that the detection rates in patients diagnosed with infectious or noninfectious
      diarrhea by GPs was the same. We also revealed the improper prescription of
      antibiotics by GPs based simply on clinical diagnoses. A further analysis of
      diagnostic accuracy and methods is required to assist GPs in improving their
      diagnoses when insufficient laboratory tests are available and budgets are
      limited.

PMID- 27886033
TI  - Efficacy of lytic Staphylococcus aureus bacteriophage against multidrug-resistant
      Staphylococcus aureus in mice.
AB  - INTRODUCTION: The use of bacteriophages as an alternative treatment method
      against multidrug-resistant bacteria has not been explored in Kenya. This study
      sought to determine the efficacy of environmentally obtained lytic bacteriophage
      against multidrug-resistant Staphylococcus aureus (MDRSA) bacterium in mice.
      METHODOLOGY: Staphylococcus aureus bacterium and S. aureus-specific lytic phage
      were isolated from sewage and wastewater collected within Nairobi County, Kenya.
      Thirty mice were randomly assigned into three groups: MDRSA infection group (n =
      20), phage-infection group (n = 5), and non-infection group (n = 5). The MDRSA
      infection group was further subdivided into three groups: clindamycin treatment
      (8 mg/kg; n = 5), lytic phage treatment (108 PFU/mL (n = 5), and a combination
      treatment of clindamycin and lytic phage (n = 5). Treatments were done at either
      24 or 72 hours post-infection (p.i), and data on efficacy, bacterial load, and
      animal physical health were collected. RESULTS: Treatment with phage was more
      effective (100%) than with clindamycin (62.25% at 24 hours p.i and 87.5% at 72
      hours p.i.) or combination treatment (75% at 24 hours p.i. and 90% at 72 hours
      p.i.) (p < 0.001). CONCLUSIONS: The results show that the environmentally
      obtained S. aureus lytic bacteriophage has therapeutic potential against MDRSA
      bacterium in mice.

PMID- 27886034
TI  - Antibiotic resistance profiles of Campylobacter species in the South Africa
      private health care sector.
AB  - INTRODUCTION: There is a dearth of surveillance data on clinical Campylobacter in
      South Africa, particularly in the private healthcare environment. We investigated
      the prevalence of resistance to first-line antibiotics used to treat
      campylobacterioses in clinical Campylobacter isolates from a private pathology
      laboratory. METHODOLOGY: Identification of the Campylobacter specific genes were
      confirmed by PCR. Minimum inhibitory concentrations were determined using the
      broth micro-dilution method against macrolides (erythromycin, azithromycin),
      fluoroquinolones (ciprofloxacin, gatifloxacin) and tetracycline. RESULTS: Seventy
      two Campylobacter isolates were identified by PCR, with 54 (75%) being classified
      as C. jejuni and 18 (25%) as C. coli. Of these, 11 (20.4%) C. jejuni and six
      (33.3%) C. coli strains were resistant to ciprofloxacin and three (7.41%) C.
      jejuni and three (16.7%) C. coli strains were resistant to gatifloxacin. The
      number of C. jejuni strains resistant to erythromycin and azithromycin was 17
      (31.5%) and 36 (50%) respectively, while the resistance of C. coli strains to
      erythromycin and azithromycin were seven (38.9%) and 14 (77.8%) respectively.
      Resistance to tetracycline was detected in 10 (55.6%) C. coli and 14 (25.9%) C.
      jejuni strains. CONCLUSION: In the light of these resistant profiles, the lack of
      a South African Campylobacter surveillance program is of concern. Relatively high
      prevalence of resistance in clinical isolates of C. jejuni and C. coli to the
      fluoroquinolones, macrolides and tetracycline used in first line treatment is of
      great concern. The efficacy treating human campylobacteriosis should thus be
      revisited.

PMID- 27886035
TI  - Developing a model to estimate the probability of bacteremia in women with
      community-onset febrile urinary tract infection.
AB  - INTRODUCTION: Among patients with urinary tract infection (UTI), bacteremic cases
      show higher mortality rates than do nonbacteremic cases. Early identification of
      bacteremic cases is crucial for severity assessment of patients with febrile UTI.
      This study aimed to identify predictors associated with bacteremia in women with
      community-onset febrile UTI and to develop a prediction model to estimate the
      probability of bacteremic cases. METHODOLOGY: This cross-sectional study included
      women consecutively hospitalized with community-onset febrile UTI at 10 hospitals
      in Korea. Multiple logistic regression identified predictors associated with
      bacteremia among candidate variables chosen from univariate analysis. A
      prediction model was developed using all predictors weighted by their regression
      coefficients. RESULTS: From July to September 2014, 383 women with febrile UTI
      were included: 115 (30.0%) bacteremic and 268 (70.0%) nonbacteremic cases. A
      prediction model consisted of diabetes mellitus (1 point), urinary tract
      obstruction by stone (2), costovertebral angle tenderness (2), a fraction of
      segmented neutrophils of > 90% (2), thrombocytopenia (2), azotemia (2), and the
      fulfillment of all criteria for systemic inflammatory response syndrome (2). The
      c statistic for the model was 0.807 (95% confidence interval [CI], 0.757-0.856).
      At a cutoff value of >= 3, the model had a sensitivity of 86.1% (95% CI, 78.1
      91.6%) and a specificity of 54.9% (95% CI, 48.7-91.6%). CONCLUSIONS: Our model
      showed a good discriminatory power for early identification of bacteremic cases
      in women with community-onset febrile UTI. In addition, our model can be used to
      identify patients at low risk for bacteremia because of its relatively high
      sensitivity.

PMID- 27886036
TI  - Prevalence, assessment, and antimicrobial resistance patterns of Salmonella from
      raw chicken eggs in Haramaya, Ethiopia.
AB  - INTRODUCTION: The presence of antimicrobial-resistant Salmonella in poultry and
      poultry products, including eggs, is a global public health concern. This study
      aimed to estimate the levels and patterns of antimicrobial resistance of
      Salmonella from chicken eggs and assess consumers' raw egg consumption and
      farmers' handling practices. METHODOLOGY: A total of 300 egg samples were
      collected from Haramaya open market (n = 150) and Haramaya University poultry
      farm (n = 150) in Ethiopia. Questionnaires were administered to egg sellers and
      buyers. A sterile cotton swab was used to sample the surface of eggs. The shells
      were sterilized and the egg content sampled. Isolation was done using the
      conventional methods for the detection of Salmonella, following the standard
      guidelines from ISO 6579. Sensitivity to 12 selected antibiotics was tested
      following the procedure of the Clinical and Laboratory Standards Institute.
      RESULTS: A level of 5.3% was observed among eggs shells from the open market and
      0% among egg shells from the poultry farm, for an overall level of 2.7%. There
      was a significant difference (p = 0.004) between the prevalence of Salmonella
      spp. in sample site and sample type. Of the antimicrobials tested, Salmonella
      isolates were all resistant to erythromycin and clindamycin. Isolates were
      sensitive to ciprofloxacin (100%) and chloramphenicol (87.5%). All isolates were
      resistant to multiple antibiotics. One-third of the consumers were found to have
      eaten raw eggs for perceived medicinal values. CONCLUSION: To minimize the
      potential contamination of eggs by pathogens, the eggs should be properly
      handled, transported, and stored.

PMID- 27886037
TI  - Hospital-acquired infection in public hospital buildings in the Philippines: Is
      the type of ventilation increasing the risk?
AB  - INTRODUCTION: Hospital-acquired infections (HAIs) are associated with increased
      morbidity and mortality, especially in developing countries. However, limited
      information is available about the risk of HAIs in naturally ventilated wards
      (NVWs) and mechanically ventilated intensive care units (MVICUs) of public
      hospitals in the Philippines. We aimed to assess the association between HAIs and
      type of ventilation in an urban tertiary care hospital in the Philippines.
      METHODOLOGY: A cross-sectional point-prevalence survey of infections was done in
      NVWs and MVICUs of a tertiary care hospital in December 2013. Multivariate
      analyses were done to examine the associations between HAIs and type of
      ventilation and other risk factors. RESULTS: Of the 224 patients surveyed, 63
      (28%) patients had 69 HAIs. Pneumonia was the most common HAI (35%). Wards near
      areas with high vehicular activity had more respiratory HAI cases. Being
      immunocompromised is a risk factor for HAI for pediatric and adult patients.
      Among pediatric patients, staying in MVICUs had a lower risk for HAIs (adjusted
      odds ratio [AOR]: 0.33; 95% confidence interval [CI]: 0.10-1.08) compared to
      staying in NVWs. For adult patients, a higher risk for HAIs (AOR: 2.41; 95% CI:
      0.29-18.20) was observed in MVICUs compared to NVWs. CONCLUSIONS: Type of
      ventilation is not a risk factor for HAIs. Patients who are immunocompromised may
      be at a higher risk for HAI. Indoor air pollution, proximity to congested main
      thoroughfare, and increased human foot traffic may contribute to the
      susceptibility of patients to HAIs. Hospital layout should be considered in
      infection control.

PMID- 27886038
TI  - Surveillance of antibiotic use in the private sector in Namibia using sales and
      claims data.
AB  - INTRODUCTION: Antibiotics are among the most commonly used therapeutic agents for
      humans globally, and their use has been associated with the development of
      resistance. The objective of this study was to identify sources for quantifying
      antibiotic usage patterns and to assess such use in ambulatory patients in the
      private health sector of Namibia. METHODOLOGY: A retrospective analysis of
      prescription claims data and sales data for the period 2008 to 2011 was
      conducted. Antibiotic use was expressed in the number of antibiotic-containing
      prescriptions and volume of units sold and then standardized using defined daily
      dose per 1,000 inhabitants per day. RESULTS: Antibiotic usage was highest in
      females (53%), in people 18-45 years of age (41%), and in Windhoek (34%).
      Overall, wholesale data showed higher antibiotic use than prescription claims
      data. However, both sources showed similar patterns of antibiotic use.
      Penicillins were the most used pharmacological group, with amoxicillin/clavulanic
      acid combination being the most used of the agents. CONCLUSION: Antibiotic use in
      the private sector of Namibia is comparable to that of high-consuming European
      countries such as Italy. A trend observed in this study was the decrease in the
      use of narrow-spectrum antibiotics in favour of broad-spectrum and newer
      antibiotics. Since this was the first study to assess antibiotic use in the
      private sector of Namibia, it could serve as a starting point for continued
      monitoring of antibiotic use in the whole of Namibia in the context of the World
      Health Organization's Global Action Plan to contain antibiotic resistance.

PMID- 27886039
TI  - Use of personal digital assistants to detect healthcare-associated infections in
      a neonatal intensive care unit in Egypt.
AB  - INTRODUCTION: Personal digital assistants (PDAs) used in electronic laboratory
      based surveillance are a promising alternative to conventional surveillance to
      detect healthcare-associated infections (HAIs). The aim of the study was to
      monitor, detect, and analyze HAIs using PDAs in a neonatal intensive care unit
      (NICU). METHODOLOGY: In this descriptive study, 1,053 neonates admitted to the
      NICU in the obstetrics and gynecology ward at the Cairo University hospital were
      included and evaluated for HAIs by collecting data using PDAs programmed by Naval
      Medical Research Unit 3, Cairo, with the definitions for HAIs provided by the
      National Healthcare Safety Network of the Centers for Disease Control and
      Prevention. Case records were reviewed three times a week over 19 months, from
      March 2012 to September 2013. RESULTS: Of 124 suspected episodes of infection
      recorded in PDAs, 89 confirmed episodes of infection were identified. HAI and
      NICU infection rates were 7.4 and 2.72/1,000 patient-days, respectively. Primary
      bloodstream infection was detected in 81 episodes and pneumonia in 8 episodes.
      The majority of infections (62%) were acquired in the ward before NICU admission.
      Klebsiella spp. was isolated most frequently (42%), followed by coagulase
      negative Staphylococci (31%). CONCLUSIONS: This study is the first to report the
      use of PDAs in surveillance to detect HAIs in the NICU in our hospital. The
      majority of infections were acquired at the obstetric care department, indicating
      the importance of implementing rigorous prevention and control programs and a
      more detailed surveillance to identify other risk factors for infections.

PMID- 27886040
TI  - Malaria knowledge and treatment adherence in a Brazilian Amazon community.
AB  - INTRODUCTION: Malaria remains an important public health problem despite recent
      scientific breakthroughs regarding knowledge about malaria and treatment
      strategies. The objective of this study was to analyze malaria patients'
      knowledge about the disease, its treatment and prevention, linking it to drug
      treatment adherence. METHODOLOGY: A descriptive, cross-sectional, epidemiological
      survey study was conducted in the district of Tres Fronteiras-MT. The study
      included 618 individuals who were interviewed and examined for Plasmodium
      infection. Of the 52 patients diagnosed with malaria, 27 were visited at home for
      an interview about malaria knowledge and treatment adherence. Treatment adherence
      was evaluated by self-reports and drug conference. RESULTS: A total of 18
      patients had satisfactory knowledge (66.6%) and 9 were evaluated as having
      unsatisfactory knowledge (33.4%) about malaria. Of the 27 malaria patients, 21
      (77.8%) reported having taken all the medication as prescribed, in the correct
      period of time and dosage, and had no medication tablets remaining. The majority
      (72.2%) of patients who had satisfactory knowledge, as well as the majority
      (88.8%) of those who had unsatisfactory knowledge, adhered to the malaria
      treatment. CONCLUSIONS: This study revealed a high proportion of patients with
      satisfactory prior knowledge about malaria and revealed that this knowledge was
      not related to disease treatment adherence. These results have implications for
      planning strategies for malaria control in the region and could contribute to the
      reduction in the cases of non-adherence to malaria treatment.

PMID- 27886041
TI  - Antimicrobial susceptibility of Pseudomonas aeruginosa before and after
      initiation of inhaled tobramycin in Bulgaria.
AB  - INTRODUCTION: In aim to achieve better infection control and possible eradication
      of the pathogens involved in chronic infections of patients with cystic fibrosis
      (CF) scientists have developed a new way to administer antimicrobials -
      inhalation. The first and so far the only available inhalable antimicrobial in
      Bulgaria is inhaled tobramycin (TOBI), introduced in 2009. We aimed to evaluate
      the antimicrobial susceptibility of Pseudomonas aeruginosa isolates from cystic
      fibrosis (CF) patients before and after initiation of TOBI in the regular
      treatment regimen. METHODOLOGY: We have determined the minimal inhibitory
      concentration (MIC) of 17 antimicrobials by the E-test (LIOFILCHEM) in sputa
      samples of 118 CF patients for the period of 2005-2014. The results were
      interpreted according to the annual Clinical and Laboratory Standards Institute
      guidelines. RESULTS: In the sputa of 70 patients a total of 102 P. aeruginosa
      isolates were found. Sixty-eight out of 102 (66.7%) were susceptible to all
      studied antimicrobials. We divided the isolates in two chronological groups:
      those collected before the introduction of TOBI as a regular treatment in 2009
      and those collected after 2009. A significant reduction (p < 0,001-0,02) in
      susceptibility for the strains after 2009 was noted towards piperacillin (100% vs
      50%), ceftazidime (100% / 77.3%), cefepime (97.9% / 68.2%), amikacin (100% /
      63.6%), gentamicin (95.7% / 40.9%), tobramycin (93.6% / 59.1%) and ciprofloxacin
      (93.6% / 45.5%). CONCLUSION: The introduction of inhaled tobramycin as a regular
      therapy for CF patients in Bulgaria lead to a significant change in antimicrobial
      susceptibility of CF P. aeruginosa.

PMID- 27886042
TI  - Molecular survey of Cytomegalovirus shedding profile in commercial pig herds in
      Brazil.
AB  - INTRODUCTION: Porcine cytomegalovirus (PCMV) causes rhinitis in both young and
      older pigs. The present study describes the detection and characterization of
      shedding profiles of PCMV in nine farrow-to-finish Brazilian swine herds.
      METHODOLOGY: Tonsil swabs from sows, nursery and grow-finish pigs of nine farrow
      to-finish commercial herds (n = 756) were evaluated for the presence of PCMV by
      PCR. RESULTS: The virus was detected in all herds. Positive samples were
      concentrated in piglets of ages varying from 40 to 60 days (nursery phase), while
      none of the sows were positive for PCMV detection. CONCLUSIONS: These findings
      corroborate the literature regarding PCMV worldwide distribution, and introduce
      the first report of PCMV shedding profile in Brazilian pig farms.

PMID- 27886043
TI  - First detection of the blaOXA-23 gene in a multidrug-resistant A. baumannii
      clinical isolate from Cochabamba, Bolivia.

PMID- 27886044
TI  - A highly sensitive Leishmania infantum chagasi isolation method from bone marrow
      and peripheral blood of adults and children.

PMID- 27886046
TI  - Views and Preferences for Nicotine Products as an Alternative to Smoking: A Focus
      Group Study of People Living with Mental Disorders.
AB  - Aims and Background: People living with mental disorders experience a
      disproportionately higher burden of tobacco-related disease than the general
      population. Long-term substitution with less harmful nicotine products could
      reduce the tobacco-related harm among this population. This study investigated
      the views and preferences of people with mental health disorders about different
      nicotine products and their use as long-term substitutes for cigarettes. Methods:
      Semi-structured focus group discussion followed by a brief questionnaire. The
      discussion transcripts were analysed for content and themes and quantitative data
      summarised with descriptive statistics. Results: Twenty-nine participants took
      part in four focus groups. Vaping devices were the most acceptable nicotine
      products discussed; however preferences for nicotine products were individual and
      varied along aesthetic, pragmatic, sensory and symbolic dimensions. The concept
      of tobacco harm reduction was unfamiliar to participants, however they generally
      agreed with the logic of replacing cigarettes with less harmful nicotine
      products. Barriers to activating tobacco harm reduction included the symbolism of
      smoking and quitting; the importance placed on health; the consumer appeal of
      alternatives; and cost implications. Discussion and Conclusions: Engaging this
      population in tobacco harm reduction options will require communication that
      challenges black and white thinking (a conceptual framework in which smoking
      cigarettes or quitting all nicotine are the only legitimate options) as in
      practice this serves to support the continuance of smoking. Consumers should be
      encouraged to trial a range of nicotine products to find the most acceptable
      alternative to smoking that reduces health harms. Providing incentives to switch
      to nicotine products could help overcome barriers to using less harmful nicotine
      products among mental health consumers.

PMID- 27886045
TI  - Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review.
AB  - Neural tube defects (NTDs) are a group of severe congenital malformations,
      induced by the combined effects of genes and the environment. The most valuable
      finding so far has been the protective effect of folic acid supplementation
      against NTDs. However, many women do not take folic acid supplements until they
      are pregnant, which is too late to prevent NTDs effectively. Long-term intake of
      folic acid-fortified food is a good choice to solve this problem, and mandatory
      folic acid fortification should be further promoted, especially in Europe, Asia
      and Africa. Vitamin B2, vitamin B-6, vitamin B-12, choline, betaine and n-3
      polyunsaturated fatty acids (PUFAs) can also reduce the NTD risk by interacting
      with the one-carbon metabolism pathway. This suggest that multivitamin B combined
      with choline, betaine and n-3 PUFAs supplementation may have a better protective
      effect against NTDs than folic acid alone. Genetic polymorphisms involved in one
      carbon metabolism are associated with NTD risk, and gene screening for women of
      childbearing age prior to pregnancy may help prevent NTDs induced by the risk
      allele. In addition, the consumption of alcohol, tea and coffee, and low intakes
      of fruit and vegetable are also associated with the increased risk of NTDs, and
      should be avoided by women of childbearing age.

PMID- 27886047
TI  - Topical Application of Apricot Kernel Extract Improves Dry Eye Symptoms in a
      Unilateral Exorbital Lacrimal Gland Excision Mouse.
AB  - The purpose of this study was to investigate the therapeutic effects of topical
      application of apricot kernel extract (AKE) in a unilateral exorbital lacrimal
      gland excision mouse model of experimental dry eye. Dry eye was induced by
      surgical removal of the lacrimal gland. Eye drops containing 0.5 or 1 mg/mL AKE
      were administered twice a day from day 3 to day 7 after surgery. Tear fluid
      volume and corneal irregularity scores were determined. In addition, we examined
      the immunohistochemical expression level of Muc4. The topical administration of
      AKE dose-dependently improved all clinical dry eye symptoms by promoting the
      secretion of tear fluid and mucin. Thus, the results of this study indicate that
      AKE may be an efficacious topical agent for treating dry eye disease.

PMID- 27886050
TI  - Design of Fresnel Lens-Type Multi-Trapping Acoustic Tweezers.
AB  - In this paper, acoustic tweezers which use beam forming performed by a Fresnel
      zone plate are proposed. The performance has been demonstrated by finite element
      analysis, including the acoustic intensity, acoustic pressure, acoustic potential
      energy, gradient force, and particle distribution. The acoustic tweezers use an
      ultrasound beam produced by a lead zirconate titanate (PZT) transducer operating
      at 2.4 MHz and 100 Vpeak-to-peak in a water medium. The design of the Fresnel
      lens (zone plate) is based on air reflection, acoustic impedance matching, and
      the Fresnel half-wave band (FHWB) theory. This acoustic Fresnel lens can produce
      gradient force and acoustic potential wells that allow the capture and
      manipulation of single particles or clusters of particles. Simulation results
      strongly indicate a good trapping ability, for particles under 150 um in
      diameter, in the minimum energy location. This can be useful for cell or
      microorganism manipulation.

PMID- 27886049
TI  - Alkynyl-Containing Peptides of Marine Origin: A Review.
AB  - Since the 1990s, a number of terminal alkynyl residue-containing cyclic/acyclic
      peptides have been identified from marine organisms, especially cyanobacteria and
      marine mollusks. This review has presented 66 peptides, which covers over 90%
      marine peptides with terminal alkynyl fatty acyl units. In fact, more than 90% of
      these peptides described in the literature are of cyanobacterial origin.
      Interestingly, all the linear peptides featured with terminal alkyne were solely
      discovered from marine cyanobacteria. The objective of this article is to provide
      an overview on the types, structural characterization of these unusual terminal
      alkynyl fatty acyl units, as well as the sources and biological functions of
      their composed peptides. Many of these peptides have a variety of biological
      activities, including antitumor, antibacterial, antimalarial, etc. Further, we
      have also discussed the evident biosynthetic origin responsible for formation of
      terminal alkynes of natural PKS (polyketide synthase)/NRPS (nonribosome peptide
      synthetase) hybrids.

PMID- 27886051
TI  - A Laminar Flow-Based Microfluidic Tesla Pump via Lithography Enabled 3D Printing.
AB  - Tesla turbine and its applications in power generation and fluid flow were
      demonstrated by Nicholas Tesla in 1913. However, its real-world implementations
      were limited by the difficulty to maintain laminar flow between rotor disks,
      transient efficiencies during rotor acceleration, and the lack of other
      applications that fully utilize the continuous flow outputs. All of the
      aforementioned limits of Tesla turbines can be addressed by scaling to the
      microfluidic flow regime. Demonstrated here is a microscale Tesla pump designed
      and fabricated using a Digital Light Processing (DLP) based 3D printer with 43 um
      lateral and 30 um thickness resolutions. The miniaturized pump is characterized
      by low Reynolds number of 1000 and a flow rate of up to 12.6 mL/min at 1200 rpm,
      unloaded. It is capable of driving a mixer network to generate microfluidic
      gradient. The continuous, laminar flow from Tesla turbines is well-suited to the
      needs of flow-sensitive microfluidics, where the integrated pump will enable
      numerous compact lab-on-a-chip applications.

PMID- 27886048
TI  - Interactions between the HIV-1 Unspliced mRNA and Host mRNA Decay Machineries.
AB  - The human immunodeficiency virus type-1 (HIV-1) unspliced transcript is used both
      as mRNA for the synthesis of structural proteins and as the packaged genome.
      Given the presence of retained introns and instability AU-rich sequences, this
      viral transcript is normally retained and degraded in the nucleus of host cells
      unless the viral protein REV is present. As such, the stability of the HIV-1
      unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm
      in order to ensure proper levels of this viral mRNA for translation and viral
      particle formation. During its journey, the HIV-1 unspliced mRNA assembles into
      highly specific messenger ribonucleoproteins (mRNPs) containing many different
      host proteins, amongst which are well-known regulators of cytoplasmic mRNA decay
      pathways such as up-frameshift suppressor 1 homolog (UPF1), Staufen double
      stranded RNA binding protein 1/2 (STAU1/2), or components of miRNA-induced
      silencing complex (miRISC) and processing bodies (PBs). More recently, the HIV-1
      unspliced mRNA was shown to contain N6-methyladenosine (m6A), allowing the
      recruitment of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), an m6A
      reader host protein involved in mRNA decay. Interestingly, these host proteins
      involved in mRNA decay were shown to play positive roles in viral gene expression
      and viral particle assembly, suggesting that HIV-1 interacts with mRNA decay
      components to successfully accomplish viral replication. This review summarizes
      the state of the art in terms of the interactions between HIV-1 unspliced mRNA
      and components of different host mRNA decay machineries.

PMID- 27886053
TI  - Automated Urban Travel Interpretation: A Bottom-up Approach for Trajectory
      Segmentation.
AB  - Understanding travel behavior is critical for an effective urban planning as well
      as for enabling various context-aware service provisions to support mobility as a
      service (MaaS). Both applications rely on the sensor traces generated by
      travellers' smartphones. These traces can be used to interpret travel modes, both
      for generating automated travel diaries as well as for real-time travel mode
      detection. Current approaches segment a trajectory by certain criteria, e.g.,
      drop in speed. However, these criteria are heuristic, and, thus, existing
      approaches are subjective and involve significant vagueness and uncertainty in
      activity transitions in space and time. Also, segmentation approaches are not
      suited for real time interpretation of open-ended segments, and cannot cope with
      the frequent gaps in the location traces. In order to address all these
      challenges a novel, state based bottom-up approach is proposed. This approach
      assumes a fixed atomic segment of a homogeneous state, instead of an event-based
      segment, and a progressive iteration until a new state is found. The research
      investigates how an atomic state-based approach can be developed in such a way
      that can work in real time, near-real time and offline mode and in different
      environmental conditions with their varying quality of sensor traces. The results
      show the proposed bottom-up model outperforms the existing event-based
      segmentation models in terms of adaptivity, flexibility, accuracy and richness in
      information delivery pertinent to automated travel behavior interpretation.

PMID- 27886052
TI  - A Melting Curve-Based Multiplex RT-qPCR Assay for Simultaneous Detection of Four
      Human Coronaviruses.
AB  - Human coronaviruses HCoV-OC43, HCoV-229E, HCoV-NL63 and HCoV-HKU1 are common
      respiratory viruses associated with acute respiratory infection. They have a
      global distribution. Rapid and accurate diagnosis of HCoV infection is important
      for the management and treatment of hospitalized patients with HCoV infection.
      Here, we developed a melting curve-based multiplex RT-qPCR assay for simultaneous
      detection of the four HCoVs. In the assay, SYTO 9 was used to replace SYBR Green
      I as the fluorescent dye, and GC-modified primers were designed to improve the
      melting temperature (Tm) of the specific amplicon. The four HCoVs were clearly
      distinguished by characteristic melting peaks in melting curve analysis. The
      detection sensitivity of the assay was 3 * 102 copies for HCoV-OC43, and 3 * 101
      copies for HCoV-NL63, HCoV-229E and HCoV-HKU1 per 30 MUL reaction. Clinical
      evaluation and sequencing confirmation demonstrated that the assay was specific
      and reliable. The assay represents a sensitive and reliable method for diagnosis
      of HCoV infection in clinical samples.

PMID- 27886054
TI  - An Improved Mobility-Based Control Protocol for Tolerating Clone Failures in
      Wireless Sensor Networks.
AB  - Nowadays, with the ubiquitous presence of the Internet of Things industry, the
      application of emerging sensor networks has become a focus of public attention.
      Unattended sensor nodes can be comprised and cloned to destroy the network
      topology. This paper proposes a novel distributed protocol and management
      technique for the detection of mobile replicas to tolerate node failures. In our
      scheme, sensors' location claims are forwarded to obtain samples only when the
      corresponding witnesses meet. Meanwhile, sequential tests of statistical
      hypotheses are applied to further detect the cloned node by witnesses. The
      combination of randomized detection based on encountering and sequential tests
      drastically reduces the routing overhead and false positive/negative rate for
      detection. Theoretical analysis and simulation results show the detection
      efficiency and reasonable overhead of the proposed method.

PMID- 27886055
TI  - Identification-While-Scanning of a Multi-Aircraft Formation Based on Sparse
      Recovery for Narrowband Radar.
AB  - It is known that the identification performance of a multi-aircraft formation
      (MAF) of narrowband radar mainly depends on the time on target (TOT). To realize
      the identification task in one rotated scan with limited TOT, the paper proposes
      a novel identification-while-scanning (IWS) method based on sparse recovery to
      maintain high rotating speed and super-resolution for MAF identification,
      simultaneously. First, a multiple chirp signal model is established for MAF in a
      single scan, where different aircraft may have different Doppler centers and
      Doppler rates. Second, based on the sparsity of MAF in the Doppler parameter
      space, a novel hierarchical basis pursuit (HBP) method is proposed to obtain
      satisfactory sparse recovery performance as well as high computational
      efficiency. Furthermore, the parameter estimation performance of the proposed IWS
      identification method is analyzed with respect to recovery condition, signal-to
      noise ratio and TOT. It is shown that an MAF can be effectively identified via
      HBP with a TOT of only about one hundred microseconds for IWS applications.
      Finally, some numerical experiment results are provided to demonstrate the
      effectiveness of the proposed method based on both simulated and real measured
      data.

PMID- 27886056
TI  - Varietal Dependence of GLVs Accumulation and LOX-HPL Pathway Gene Expression in
      Four Vitis vinifera Wine Grapes.
AB  - Variety is one of the major factors influencing grape and wine aromatic
      characteristics. Green leaf volatiles (GLVs), derived from lipoxygenase
      hydroperoxides lyase (LOX-HPL) pathway, are important components for the aromatic
      quality of grapes and wines. However, the varietal difference regarding GLVs
      accumulation and related gene expression are poorly studied. This work exhibited
      that the accumulation of various GLVs and the expression of LOX-HPL pathway genes
      in four Vitis vinifera wine grape cultivars: Syrah, Muscat Tchervine,
      Gewurztraminer and Chardonnay. The results showed a variety dependence of GLVs
      profile. Muscat Tchervine harvested grapes contained less C6 aldehydes and the
      most abundant esters, which corresponded to very low VvLOXA and VvHPL1 expression
      abundance as well as high VvAAT transcript in this variety. High expression level
      of both VvLOXA and VvHPL1 paralleled with higher level of C6 aldehydes together
      with higher alcohols in Syrah grape. Gewurztraminer and Chardonnay grapes had
      high aldehydes and alcohols as well as low esters, which were resulted from their
      higher expression level of VvLOXA or VvHPL1 and lower VvAAT. From these above
      corresponding relations, it is concluded that VvLOXA, VvHPL1 and VvAAT in the LOX
      HPL pathway are targets for altering GLVs composition in the grape varieties.

PMID- 27886057
TI  - Age-Related Modulations of AQP4 and Caveolin-1 in the Hippocampus Predispose the
      Toxic Effect of Phoneutria nigriventer Spider Venom.
AB  - We have previously demonstrated that Phoneutria nigriventer venom (PNV) causes
      blood-brain barrier (BBB) breakdown, swelling of astrocytes end-feet and fluid
      permeation into brain interstitium in rats. Caveolae and water channels respond
      to BBB alterations by co-participation in shear stress response and edema
      formation/resolution. Herein, we showed post-natal developmental-related changes
      of two BBB-associated transporter proteins: the endothelial caveolin-1 (Cav-1),
      the major scaffolding protein from caveolae frame, and the astroglial aquaporin-4
      (AQP4), the main water channel protein expressed in astrocytic peri-vascular end
      feet processes, in the hippocampus of rats intraperitoneally-administered PNV.
      Western blotting protein levels; immunohistochemistry (IHC) protein distribution
      in CA1, CA2, and CA3 subfields; and gene expression by Real Time-Polymerase Chain
      Reaction (qPCR) were assessed in post-natal Day 14 (P14) and 8-10-week-old rats
      over critical periods of envenomation. The intensity and duration of the toxic
      manifestations indicate P14 neonate rats more vulnerable to PNV than adults.
      Histologically, the capillaries of P14 and 8-10-week-old rats treated with PNV
      showed perivascular edema, while controls did not. The intensity of the toxic
      manifestations in P14 decreases temporally (2 > 5 > 24 h), while inversely the
      expression of AQP4 and Cav-1 peaked at 24 h when clinically PNV-treated animals
      do not differ from saline controls. IHC of AQP4 revealed that hippocampal CA1
      showed the least expression at 2 h when toxic manifestation was maximal. Subfield
      IHC quantification revealed that in P14 rats Cav-1 peaked at 24 h when toxic
      manifestations were absent, whereas in 8-10-week-old rats Cav-1 peaked at 2 h
      when toxic signs were highest, and progressively attenuated such increases until
      24 h, remaining though significantly above baseline. Considering astrocyte
      endothelial physical and functional interactions, we hypothesize that age-related
      modulations of AQP4 and Cav-1 might be linked both to changes in functional
      properties of astrocytes during post-natal development and in the BBB breakdown
      induced by the venom of P. nigriventer.

PMID- 27886058
TI  - Optical Aptamer Probes of Fluorescent Imaging to Rapid Monitoring of Circulating
      Tumor Cell.
AB  - Fluorescence detecting of exogenous EpCAM (epithelial cell adhesion molecule) or
      muc1 (mucin1) expression correlated to cancer metastasis using nanoparticles
      provides pivotal information on CTC (circulating tumor cell) occurrence in a
      noninvasive tool. In this study, we study a new skill to detect extracellular
      EpCAM/muc1 using quantum dot-based aptamer beacon (QD-EpCAM/muc1 ALB (aptamer
      linker beacon). The QD-EpCAM/muc1 ALB was designed using QDs (quantum dots) and
      probe. The EpCAM/muc1-targeting aptamer contains a Ep-CAM/muc1 binding sequence
      and BHQ1 (black hole quencher 1) or BHQ2 (black hole quencher2). In the absence
      of target EpCAM/muc1, the QD-EpCAM/muc1 ALB forms a partial duplex loop-like
      aptamer beacon and remained in quenched state because the BHQ1/2 quenches the
      fluorescence signal-on of the QD-EpCAM/muc1 ALB. The binding of EpCAM/muc1 of CTC
      to the EpCAM/muc1 binding aptamer sequence of the EpCAM/muc1-targeting
      oligonucleotide triggered the dissociation of the BHQ1/2 quencher and subsequent
      signal-on of a green/red fluorescence signal. Furthermore, acute inflammation was
      stimulated by trigger such as caerulein in vivo, which resulted in increased
      fluorescent signal of the cy5.5-EpCAM/muc1 ALB during cancer metastasis due to
      exogenous expression of EpCAM/muc1 in Panc02-implanted mouse model.

PMID- 27886060
TI  - Finding Harmony between Science and Art in Pediatric Cardiology: Acknowledging
      When Being "Objective" May Not Truly Be Objective.
AB  - As pediatric cardiologists, we greatly value objective decision-making and logic.
      [...].

PMID- 27886059
TI  - Regulation of Intrinsic and Extrinsic Apoptotic Pathways in Osteosarcoma Cells
      Following Oleandrin Treatment.
AB  - Our previous study has reported the anti-tumor effect of oleandrin on
      osteosarcoma (OS) cells. In the current study, we mainly explored its potential
      regulation on intrinsic and extrinsic apoptotic pathway in OS cells. Cells
      apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential
      (MMP) were detected using fluorescence staining and flow cytometry. Caspase-3
      activity was detected using a commercial kit. The levels of cytoplasmic
      cytochrome c, mitochondrial cytochrome c, bcl-2, bax, caspase-9, Fas, FasL,
      caspase-8 and caspase-3 were detected by Western blotting. z-VAD-fmk was applied
      to block both intrinsic and extrinsic apoptosis pathways, and cells apoptosis was
      also tested. Furthermore, we used z-LEHD-fmk and Fas blocking antibody to inhibit
      intrinsic and extrinsic pathways, separately, and the selectivity of oleandrin on
      these pathways was explored. Results showed that oleandrin induced the apoptosis
      of OS cells, which was accompanied by an increase in ROS and a decrease in MMP.
      Furthermore, cytochrome c level was reduced in mitochondria but elevated in the
      cytoplasm. Caspase-3 activity was enhanced by oleandrin in a concentration- and
      time-dependent manner. Oleandrin also down-regulated the expression of bcl-2, but
      up-regulated bax, caspase-9, Fas, FasL, caspase-8 and caspase-3. In addition, the
      suppression of both apoptotic pathways by z-VAD-fmk greatly reverted the
      oleandrin-induced apoptosis. Moreover, the suppression of one pathway by a
      corresponding inhibitor did not affect the regulation of oleandrin on another
      pathway. Taken together, we concluded that oleandrin induced apoptosis of OS
      cells via activating both intrinsic and extrinsic apoptotic pathways.

PMID- 27886061
TI  - Accelerating Families of Fuzzy K-Means Algorithms for Vector Quantization
      Codebook Design.
AB  - The performance of signal processing systems based on vector quantization depends
      on codebook design. In the image compression scenario, the quality of the
      reconstructed images depends on the codebooks used. In this paper, alternatives
      are proposed for accelerating families of fuzzy K-means algorithms for codebook
      design. The acceleration is obtained by reducing the number of iterations of the
      algorithms and applying efficient nearest neighbor search techniques. Simulation
      results concerning image vector quantization have shown that the acceleration
      obtained so far does not decrease the quality of the reconstructed images.
      Codebook design time savings up to about 40% are obtained by the accelerated
      versions with respect to the original versions of the algorithms.

PMID- 27886062
TI  - Microarray Expression Profiling of Long Non-Coding RNAs Involved in
      Nasopharyngeal Carcinoma Metastasis.
AB  - Increasing evidence has demonstrated a significant role for long non-coding RNAs
      (lncRNAs) in tumorigenesis. However, their functions in nasopharyngeal carcinoma
      (NPC) metastasis remain largely unknown. In this study, a model comparing high
      and low metastatic NPC cell lines (5-8F vs. 6-10B and S18 vs. S26) was
      constructed to determine the expression profile of lncRNAs using the microarray
      analysis, and we found 167 lncRNAs and 209 mRNAs were differentially expressed.
      Bioinformatic analysis indicated that the dysregulated mRNAs participated in
      important biological regulatory functions in NPC. Validation of 26 significantly
      dysregulated lncRNAs by qRT-PCR showed the expression patterns of 22 lncRNAs were
      in accordance with the microarray data. Furthermore, the expression level of
      ENST00000470135, which was the most upregulated lncRNA in high metastatic cell
      lines, was significantly higher in NPC cell lines and tissues with lymph node
      metastasis (LNM) and knocking down ENST00000470135 suppressed the migration,
      invasion and proliferation of NPC cells in vitro. In conclusion, our study
      revealed expression patterns of lncRNAs in NPC metastasis. The dysregulated
      lncRNAs may act as novel biomarkers and therapeutic targets for NPC.

PMID- 27886064
TI  - Probiotic Supplements Beneficially Affect Tryptophan-Kynurenine Metabolism and
      Reduce the Incidence of Upper Respiratory Tract Infections in Trained Athletes: A
      Randomized, Double-Blinded, Placebo-Controlled Trial.
AB  - BACKGROUND: Prolonged intense exercise has been associated with transient
      suppression of immune function and an increased risk of infections. In this
      context, the catabolism of amino acid tryptophan via kynurenine may play an
      important role. The present study examined the effect of a probiotic supplement
      on the incidence of upper respiratory tract infections (URTI) and the metabolism
      of aromatic amino acids after exhaustive aerobic exercise in trained athletes
      during three months of winter training. METHODS: Thirty-three highly trained
      individuals were randomly assigned to probiotic (PRO, n = 17) or placebo (PLA, n
      = 16) groups using double blind procedures, receiving either 1 * 1010 colony
      forming units (CFU) of a multi-species probiotic (Bifidobacterium bifidum W23,
      Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus
      W22, Lactobacillus brevis W63, and Lactococcus lactis W58) or placebo once per
      day for 12 weeks. The serum concentrations of tryptophan, phenylalanine and their
      primary catabolites kynurenine and tyrosine, as well as the concentration of the
      immune activation marker neopterin were determined at baseline and after 12
      weeks, both at rest and immediately after exercise. Participants completed a
      daily diary to identify any infectious symptoms. RESULTS: After 12 weeks of
      treatment, post-exercise tryptophan levels were lowered by 11% (a significant
      change) in the PLA group compared to the concentrations measured before the
      intervention (p = 0.02), but remained unchanged in the PRO group. The ratio of
      subjects taking the placebo who experienced one or more URTI symptoms was
      increased 2.2-fold compared to those on probiotics (PLA 0.79, PRO 0.35; p =
      0.02). CONCLUSION: Data indicate reduced exercise-induced tryptophan degradation
      rates in the PRO group. Daily supplementation with probiotics limited exercise
      induced drops in tryptophan levels and reduced the incidence of URTI, however,
      did not benefit athletic performance.

PMID- 27886065
TI  - Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate
      Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for
      Cartilage Tissue Engineering.
AB  - Glucosamine (GlcN) fulfills many of the requirements as an ideal component in
      scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a
      gelatin/hyaluronic acid (GH) cryogel scaffold could provide biological cues in
      maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with
      GlcN may also decrease the crosslinking density and modulate the mechanical
      properties of the cryogel scaffold, which may be beneficial as physical cues for
      chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9%
      GlcN (GH-GlcN9) and 16% GlcN (GH-GlcN16) by carbodiimide-mediated crosslinking
      reactions at -16  degrees C. The crosslinking density and the mechanical
      properties of the cryogel matrix could be tuned by adjusting the content of GlcN
      used during cryogel preparation. In general, incorporation of GlcN did not
      influence scaffold pore size and ultimate compressive strain but increased
      porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation
      rate in hyaluronidase and collagenase solutions. On the contrary, the Young's
      modulus, storage modulus, ultimate compressive stress, energy dissipation level,
      and rate of stress relaxation decreased by increasing the GlcN content in the
      cryogel. The release of GlcN from the scaffolds in the culture medium of
      chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7
      days for GH-GlcN9. In vitro cell culture experiments using rabbit articular
      chondrocytes revealed that GlcN incorporation affected cell proliferation,
      morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed
      the best performance in maintaining chondrogenic phenotype with reduced cell
      proliferation rate but enhanced glycosaminoglycans (GAGs) and type II collagen
      (COL II) secretion. Quantitative real-time polymerase chain reaction also showed
      time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan
      and Sox9) for GH-GlcN16. Implantation of chondrocytes/GH-GlcN16 constructs into
      full-thickness articular cartilage defects of rabbits could regenerate
      neocartilage with positive staining for GAGs and COL II. The GH-GlcN16 cryogel
      will be suitable as a scaffold for the treatment of articular cartilage defects.

PMID- 27886066
TI  - Importance of Heat and Pressure for Solubilization of Recombinant Spider Silk
      Proteins in Aqueous Solution.
AB  - The production of recombinant spider silk proteins continues to be a key area of
      interest for a number of research groups. Several key obstacles exist in their
      production as well as in their formulation into useable products. The original
      reported method to solubilize recombinant spider silk proteins (rSSp) in an
      aqueous solution involved using microwaves to quickly generate heat and pressure
      inside of a sealed vial containing rSSp and water. Fibers produced from this
      system are remarkable in their mechanical ability and demonstrate the ability to
      be stretched and recover 100 times. The microwave method dissolves the rSSPs with
      dissolution time increasing with higher molecular weight constructs, increasing
      concentration of rSSPs, protein type, and salt concentration. It has proven
      successful in solvating a number of different rSSPs including native-like
      sequences (MaSp1, MaSp2, piriform, and aggregate) as well as chimeric sequences
      (FlAS) in varied concentrations that have been spun into fibers and formed into
      films, foams, sponges, gels, coatings, macro and micro spheres and adhesives. The
      system is effective but inherently unpredictable and difficult to control.
      Provided that the materials that can be generated from this method of dissolution
      are impressive, an alternative means of applying heat and pressure that is
      controllable and predictable has been developed. Results indicate that there are
      combinations of heat and pressure (135  degrees C and 140 psi) that result in
      maximal dissolution without degrading the recombinant MaSp2 protein tested, and
      that heat and pressure are the key elements to the method of dissolution.

PMID- 27886067
TI  - A Real-Time Kinect Signature-Based Patient Home Monitoring System.
AB  - Assessment of body kinematics during performance of daily life activities at home
      plays a significant role in medical condition monitoring of elderly people and
      patients with neurological disorders. The affordable and non-wearable Microsoft
      Kinect ("Kinect") system has been recently used to estimate human subject
      kinematic features. However, the Kinect suffers from a limited range and angular
      coverage, distortion in skeleton joints' estimations, and erroneous multiplexing
      of different subjects' estimations to one. This study addresses these limitations
      by incorporating a set of features that create a unique "Kinect Signature". The
      Kinect Signature enables identification of different subjects in the scene,
      automatically assign the kinematics feature estimations only to the subject of
      interest, and provide information about the quality of the Kinect-based
      estimations. The methods were verified by a set of experiments, which utilize
      real-time scenarios commonly used to assess motor functions in elderly subjects
      and in subjects with neurological disorders. The experiment results indicate that
      the skeleton based Kinect Signature features can be used to identify different
      subjects in high accuracy. We demonstrate how these capabilities can be used to
      assign the Kinect estimations to the Subject of Interest, and exclude low quality
      tracking features. The results of this work can help in establishing reliable
      kinematic features, which can assist in future to obtain objective scores for
      medical analysis of patient condition at home while not restricted to perform
      daily life activities.

PMID- 27886063
TI  - d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action
      and Pharmacology.
AB  - d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and
      psychotic-like symptoms, especially at high doses. It is indeed used as a
      pharmacological model of psychosis in preclinical research. The goal of this
      review was to understand the mechanism of action of psychotic-like effects of
      LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles'
      reference lists for preclinical studies regarding the mechanism of action
      involved in the psychotic-like effects induced by LSD. LSD's mechanism of action
      is pleiotropic, primarily mediated by the serotonergic system in the Dorsal
      Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist.
      LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating
      dopamine D2, Trace Amine Associate receptor 1 (TAAR1) and 5-HT2A. More studies
      clarifying the mechanism of action of the psychotic-like symptoms or psychosis
      induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic
      mechanism involving serotonergic, dopaminergic, and glutamatergic
      neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the
      therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs
      with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR1
      receptors.

PMID- 27886068
TI  - Effects of Sampling Conditions and Environmental Factors on Fecal Volatile
      Organic Compound Analysis by an Electronic Nose Device.
AB  - Prior to implementation of volatile organic compound (VOC) analysis in clinical
      practice, substantial challenges, including methodological, biological and
      analytical difficulties are faced. The aim of this study was to evaluate the
      influence of several sampling conditions and environmental factors on fecal VOC
      profiles, analyzed by an electronic nose (eNose). Effects of fecal sample mass,
      water content, duration of storage at room temperature, fecal sample temperature,
      number of freeze-thaw cycles and effect of sampling method (rectal swabs vs.
      fecal samples) on VOC profiles were assessed by analysis of totally 725 fecal
      samples by means of an eNose (Cyranose320(r)). Furthermore, fecal VOC profiles of
      totally 1285 fecal samples from 71 infants born at three different hospitals were
      compared to assess the influence of center of origin on VOC outcome. We observed
      that all analyzed variables significantly influenced fecal VOC composition. It
      was feasible to capture a VOC profile using rectal swabs, although this differed
      significantly from fecal VOC profiles of similar subjects. In addition, 1285
      fecal VOC-profiles could significantly be discriminated based on center of birth.
      In conclusion, standardization of methodology is necessary before fecal VOC
      analysis can live up to its potential as diagnostic tool in clinical practice.

PMID- 27886069
TI  - Co-Creating the Cities of the Future.
AB  - In recent years, the evolution of urban environments, jointly with the progress
      of the Information and Communication sector, have enabled the rapid adoption of
      new solutions that contribute to the growth in popularity of Smart Cities.
      Currently, the majority of the world population lives in cities encouraging
      different stakeholders within these innovative ecosystems to seek new solutions
      guaranteeing the sustainability and efficiency of such complex environments. In
      this work, it is discussed how the experimentation with IoT technologies and
      other data sources form the cities can be utilized to co-create in the OrganiCity
      project, where key actors like citizens, researchers and other stakeholders shape
      smart city services and applications in a collaborative fashion. Furthermore, a
      novel architecture is proposed that enables this organic growth of the future
      cities, facilitating the experimentation that tailors the adoption of new
      technologies and services for a better quality of life, as well as agile and
      dynamic mechanisms for managing cities. In this work, the different components
      and enablers of the OrganiCity platform are presented and discussed in detail and
      include, among others, a portal to manage the experiment life cycle, an Urban
      Data Observatory to explore data assets, and an annotations component to indicate
      quality of data, with a particular focus on the city-scale opportunistic data
      collection service operating as an alternative to traditional communications.

PMID- 27886070
TI  - Molecularly Imprinted Filtering Adsorbents for Odor Sensing.
AB  - Versatile odor sensors that can discriminate among huge numbers of environmental
      odorants are desired in many fields, including robotics, environmental
      monitoring, and food production. However, odor sensors comparable to an animal's
      nose have not yet been developed. An animal's olfactory system recognizes odor
      clusters with specific molecular properties and uses this combinatorial
      information in odor discrimination. This suggests that measurement and clustering
      of odor molecular properties (e.g., polarity, size) using an artificial sensor is
      a promising approach to odor sensing. Here, adsorbents composed of composite
      materials with molecular recognition properties were developed for odor sensing.
      The selectivity of the sensor depends on the adsorbent materials, so specific
      polymeric materials with particular solubility parameters were chosen to adsorb
      odorants with various properties. The adsorption properties of the adsorbents
      could be modified by mixing adsorbent materials. Moreover, a novel molecularly
      imprinted filtering adsorbent (MIFA), composed of an adsorbent substrate covered
      with a molecularly imprinted polymer (MIP) layer, was developed to improve the
      odor molecular recognition ability. The combination of the adsorbent and MIP
      layer provided a higher specificity toward target molecules. The MIFA thus
      provides a useful technique for the design and control of adsorbents with
      adsorption properties specific to particular odor molecules.

PMID- 27886072
TI  - Peroxynitrite Sensor Based on a Screen Printed Carbon Electrode Modified with a
      Poly(2,6-dihydroxynaphthalene) Film.
AB  - For the first time the electropolymerization of 2,6-dihydroxynaphthalene (2,6
      DHN) on a screen printed carbon electrode (SPCE) was investigated and evaluated
      for peroxynitrite (PON) detection. Cyclic voltammetry was used to electrodeposit
      the poly(2,6-DHN) on the carbon electrode surface. The surface morphology and
      structure of poly(2,6-DHN) film were investigated by SEM and FTIR analysis, and
      the electrochemical features by cyclic voltammetry. The poly(2,6-DHN)/SPCE sensor
      showed excellent electrocatalytic activity for PON oxidation in alkaline
      solutions at very low potentials (0-100 mV vs. Ag/AgCl pseudoreference). An
      amperometric FIA (flow injection analysis) system based on the developed sensor
      was optimized for PON measurements and a linear concentration range from 2 to 300
      MUM PON, with a LOD of 0.2 MUM, was achieved. The optimized sensor inserted in
      the FIA system exhibited good sensitivity (4.12 nA.MUM-1), selectivity, stability
      and intra-/inter-electrode reproducibility for PON determination.

PMID- 27886071
TI  - Case Formulation in Young People with Post-Traumatic Stress Disorder and First
      Episode Psychosis.
AB  - BACKGROUND: Evidence based treatment interventions for young people with first
      episode psychosis (FEP) and trauma histories is lacking. Although case
      formulation (CF) has been widely regarded in cognitive behavioural therapy
      manuals as beneficial, there is limited empirical research examining how clients
      and therapists experience the process. AIM: This study aimed to explore young
      people's reactions to CF in treatment for PTSD (post-traumatic stress disorder)
      and FEP. METHOD: Semi-structured interviews were conducted with three
      participants (aged 19-20) with FEP and PTSD and their therapists, after they had
      completed a trauma-focused treatment program with a CF component. Transcripts
      were analysed using an interpretative phenomenological approach and themes were
      derived. RESULTS: Two themes related to participants' experiences were identified
      from the analysis: (1) Developing Insight; (2) A challenging experience; and two
      themes from the therapists: (1) Doing the case formulation; (2) Value of case
      formulation. Participants and therapists reported benefits in making connections
      between current symptoms and past trauma. Participants viewed the process as
      challenging. CONCLUSION: Results suggest a potential discrepancy between the
      experience of the case formulation process for clients and therapists.

PMID- 27886073
TI  - Effect of Six-Month Diet Intervention on Sleep among Overweight and Obese Men
      with Chronic Insomnia Symptoms: A Randomized Controlled Trial.
AB  - Growing evidence suggests that diet alteration affects sleep, but this has not
      yet been studied in adults with insomnia symptoms. We aimed to determine the
      effect of a six-month diet intervention on sleep among overweight and obese (Body
      mass index, BMI >= 25 kg/m2) men with chronic insomnia symptoms. Forty-nine men
      aged 30-65 years with chronic insomnia symptoms were randomized into diet (n =
      28) or control (n = 21) groups. The diet group underwent a six-month
      individualized diet intervention with three face-to-face counseling sessions and
      online supervision 1-3 times per week; 300-500 kcal/day less energy intake and
      optimized nutrient composition were recommended. Controls were instructed to
      maintain their habitual lifestyle. Sleep parameters were determined by
      piezoelectric bed sensors, a sleep diary, and a Basic Nordic sleep questionnaire.
      Compared to the controls, the diet group had shorter objective sleep onset
      latency after intervention. Within the diet group, prolonged objective total
      sleep time, improved objective sleep efficiency, lower depression score, less
      subjective nocturnal awakenings, and nocturia were found after intervention. In
      conclusion, modest energy restriction and optimized nutrient composition shorten
      sleep onset latency in overweight and obese men with insomnia symptoms.

PMID- 27886074
TI  - Eleventh International Foamy Virus Conference-Meeting Report.
AB  - The Eleventh International Foamy Virus Conference took place on 9-10 June 2016 at
      the Institut Pasteur, Paris, France. The meeting reviewed progress on foamy virus
      (FV) research, as well as related current topics in retrovirology. FVs are
      complex retroviruses that are widespread in several animal species. Several
      research topics on these viruses are relevant to human health: cross-species
      transmission and viral emergence, vectors for gene therapy, development of
      antiretroviral drugs, retroviral evolution and its influence on the human genome.
      In this article, we review the conference presentations on these viruses and
      highlight the major questions to be answered.

PMID- 27886075
TI  - The Expanding Family of Virophages.
AB  - Virophages replicate with giant viruses in the same eukaryotic cells. They are a
      major component of the specific mobilome of mimiviruses. Since their discovery in
      2008, five other representatives have been isolated, 18 new genomes have been
      described, two of which being nearly completely sequenced, and they have been
      classified in a new viral family, Lavidaviridae. Virophages are small viruses
      with approximately 35-74 nm large icosahedral capsids and 17-29 kbp large double
      stranded DNA genomes with 16-34 genes, among which a very small set is shared
      with giant viruses. Virophages have been isolated or detected in various
      locations and in a broad range of habitats worldwide, including the deep ocean
      and inland. Humans, therefore, could be commonly exposed to virophages, although
      currently limited evidence exists of their presence in humans based on serology
      and metagenomics. The distribution of virophages, the consequences of their
      infection and the interactions with their giant viral hosts within eukaryotic
      cells deserve further research.

PMID- 27886076
TI  - Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic
      Properties and Induce Protective Immune Responses.
AB  - Inactivated vaccines are commonly produced by incubating pathogens with chemicals
      such as formaldehyde or beta-propiolactone. This is a time-consuming process, the
      inactivation efficiency displays high variability and extensive downstream
      procedures are often required. Moreover, application of chemicals alters the
      antigenic components of the viruses or bacteria, resulting in reduced antibody
      specificity and therefore stimulation of a less effective immune response. An
      alternative method for inactivation of pathogens is ionizing radiation. It acts
      very fast and predominantly damages nucleic acids, conserving most of the
      antigenic structures. However, currently used irradiation technologies (mostly
      gamma-rays and high energy electrons) require large and complex shielding
      constructions to protect the environment from radioactivity or X-rays generated
      during the process. This excludes them from direct integration into biological
      production facilities. Here, low-energy electron irradiation (LEEI) is presented
      as an alternative inactivation method for pathogens in liquid solutions. LEEI can
      be used in normal laboratories, including good manufacturing practice (GMP)- or
      high biosafety level (BSL)-environments, as only minor shielding is necessary. We
      show that LEEI efficiently inactivates different viruses (influenza A (H3N8),
      porcine reproductive and respiratory syndrome virus (PRRSV), equine herpesvirus 1
      (EHV-1)) and bacteria (Escherichia coli) and maintains their antigenicity.
      Moreover, LEEI-inactivated influenza A viruses elicit protective immune responses
      in animals, as analyzed by virus neutralization assays and viral load
      determination upon challenge. These results have implications for novel ways of
      developing and manufacturing inactivated vaccines with improved efficacy.

PMID- 27886077
TI  - Magnetofection Enhances Lentiviral-Mediated Transduction of Airway Epithelial
      Cells through Extracellular and Cellular Barriers.
AB  - Gene transfer to airway epithelial cells is hampered by extracellular (mainly
      mucus) and cellular (tight junctions) barriers. Magnetofection has been used to
      increase retention time of lentiviral vectors (LV) on the cellular surface. In
      this study, magnetofection was investigated in airway epithelial cell models
      mimicking extracellular and cellular barriers. Bronchiolar epithelial cells (H441
      line) were evaluated for LV-mediated transduction after polarization onto filters
      and dexamethasone (dex) treatment, which induced hemicyst formation, with or
      without magnetofection. Sputum from cystic fibrosis (CF) patients was overlaid
      onto cells, and LV-mediated transduction was evaluated in the absence or presence
      of magnetofection. Magnetofection of unpolarized H441 cells increased the
      transduction with 50 MOI (multiplicity of infection, i.e., transducing
      units/cell) up to the transduction obtained with 500 MOI in the absence of
      magnetofection. Magnetofection well-enhanced LV-mediated transduction in mucus
      layered cells by 20.3-fold. LV-mediated transduction efficiency decreased in dex
      induced hemicysts in a time-dependent fashion. In dome-forming cells, zonula
      occludens-1 (ZO-1) localization at the cell borders was increased by dex
      treatment. Under these experimental conditions, magnetofection significantly
      increased LV transduction by 5.3-fold. In conclusion, these results show that
      magnetofection can enhance LV-mediated gene transfer into airway epithelial cells
      in the presence of extracellular (sputum) and cellular (tight junctions)
      barriers, representing CF-like conditions.

PMID- 27886080
TI  - Three-Dimensional Object Recognition and Registration for Robotic Grasping
      Systems Using a Modified Viewpoint Feature Histogram.
AB  - This paper presents a novel 3D feature descriptor for object recognition and to
      identify poses when there are six-degrees-of-freedom for mobile manipulation and
      grasping applications. Firstly, a Microsoft Kinect sensor is used to capture 3D
      point cloud data. A viewpoint feature histogram (VFH) descriptor for the 3D point
      cloud data then encodes the geometry and viewpoint, so an object can be
      simultaneously recognized and registered in a stable pose and the information is
      stored in a database. The VFH is robust to a large degree of surface noise and
      missing depth information so it is reliable for stereo data. However, the pose
      estimation for an object fails when the object is placed symmetrically to the
      viewpoint. To overcome this problem, this study proposes a modified viewpoint
      feature histogram (MVFH) descriptor that consists of two parts: a surface shape
      component that comprises an extended fast point feature histogram and an extended
      viewpoint direction component. The MVFH descriptor characterizes an object's pose
      and enhances the system's ability to identify objects with mirrored poses.
      Finally, the refined pose is further estimated using an iterative closest point
      when the object has been recognized and the pose roughly estimated by the MVFH
      descriptor and it has been registered on a database. The estimation results
      demonstrate that the MVFH feature descriptor allows more accurate pose
      estimation. The experiments also show that the proposed method can be applied in
      vision-guided robotic grasping systems.

PMID- 27886081
TI  - Improved Goldstein Interferogram Filter Based on Local Fringe Frequency
      Estimation.
AB  - The quality of an interferogram, which is limited by various phase noise, will
      greatly affect the further processes of InSAR, such as phase unwrapping.
      Interferometric SAR (InSAR) geophysical measurements', such as height or
      displacement, phase filtering is therefore an essential step. In this work, an
      improved Goldstein interferogram filter is proposed to suppress the phase noise
      while preserving the fringe edges. First, the proposed adaptive filter step,
      performed before frequency estimation, is employed to improve the estimation
      accuracy. Subsequently, to preserve the fringe characteristics, the estimated
      fringe frequency in each fixed filtering patch is removed from the original noisy
      phase. Then, the residual phase is smoothed based on the modified Goldstein
      filter with its parameter alpha dependent on both the coherence map and the
      residual phase frequency. Finally, the filtered residual phase and the removed
      fringe frequency are combined to generate the filtered interferogram, with the
      loss of signal minimized while reducing the noise level. The effectiveness of the
      proposed method is verified by experimental results based on both simulated and
      real data.

PMID- 27886082
TI  - Ultra-Low Power Optical Sensor for Xylophagous Insect Detection in Wood.
AB  - The early detection of pests is key for the maintenance of high-value
      masterpieces and historical buildings made of wood. In this work, we the present
      detailed design of an ultra-low power sensor device that permits the continuous
      monitoring of the presence of termites and other xylophagous insects. The
      operating principle of the sensor is based on the variations of reflected light
      induced by the presence of termites, and specific processing algorithms that deal
      with the behavior of the electronics and the natural ageing of components. With a
      typical CR2032 lithium battery, the device lasts more than nine years, and is
      ideal for incorporation in more complex monitoring systems where maintenance
      tasks should be minimized.

PMID- 27886079
TI  - Cerebellar Intermittent Theta-Burst Stimulation and Motor Control Training in
      Individuals with Cervical Dystonia.
AB  - BACKGROUND: There is emerging evidence that cervical dystonia is a neural network
      disorder with the cerebellum as a key node. The cerebellum may provide a target
      for neuromodulation as a therapeutic intervention in cervical dystonia.
      OBJECTIVE: This study aimed to assess effects of intermittent theta-burst
      stimulation of the cerebellum on dystonia symptoms, quality of life, hand motor
      dexterity and cortical neurophysiology using transcranial magnetic stimulation.
      METHODS: Sixteen participants with cervical dystonia were randomised into real or
      sham stimulation groups. Cerebellar neuromodulation was combined with motor
      training for the neck and an implicit learning task. The intervention was
      delivered over 10 working days. Outcome measures included dystonia severity and
      pain, quality of life, hand dexterity, and motor-evoked potentials and cortical
      silent periods recorded from upper trapezius muscles. Assessments were taken at
      baseline and after 5 and 10 days, with quality of life also measured 4 and 12
      weeks later. RESULTS: Intermittent theta-burst stimulation improved dystonia
      severity (Day 5, -5.44 points; p = 0.012; Day 10, -4.6 points; p = 0.025),
      however, effect sizes were small. Quality of life also improved (Day 5, -10.6
      points, p = 0.012; Day 10, -8.6 points, p = 0.036; Week 4, -12.5 points, p =
      0.036; Week 12, -12.4 points, p = 0.025), with medium or large effect sizes.
      There was a reduction in time to complete the pegboard task pre to post
      intervention (both p < 0.008). Cortical neurophysiology was unchanged by
      cerebellar neuromodulation. CONCLUSION: Intermittent theta-burst stimulation of
      the cerebellum may improve cervical dystonia symptoms, upper limb motor control
      and quality of life. The mechanism likely involves promoting neuroplasticity in
      the cerebellum although the neurophysiology remains to be elucidated. Cerebellar
      neuromodulation may have potential as a novel treatment intervention for cervical
      dystonia, although larger confirmatory studies are required.

PMID- 27886078
TI  - Effects of Two-Year Vitamin B12 and Folic Acid Supplementation on Depressive
      Symptoms and Quality of Life in Older Adults with Elevated Homocysteine
      Concentrations: Additional Results from the B-PROOF Study, an RCT.
AB  - Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing
      vitamin B12 and folic acid may reduce depressive symptoms and improve health
      related quality of life (HR-QoL) in older adults. This study aimed to test this
      hypothesis in a randomized controlled trial. Participants (N = 2919, >=65 years,
      Hcy concentrations >=12 umol/L) received either 500 ug vitamin B12 and 400 ug
      folic acid daily or placebo for two years. Both tablets contained 15 ug vitamin
      D3. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS
      15). HR-QoL was assessed with the SF-12 Mental and Physical component summary
      scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two
      year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy
      concentrations decreased more in the intervention group, but two-year change
      scores of the GDS-15 and three of four HR-QoL measures did not differ between
      groups. The EQ-5D Index score declined less in the intervention group than in the
      placebo group (mean change 0.00 vs. -0.02, p = 0.004). In conclusion, two-year
      supplementation with vitamin B12 and folic acid in older adults with
      hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce
      depressive symptoms, but it may have a small positive effect on HR-QoL.

PMID- 27886083
TI  - A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women.
AB  - This prospective study sought to investigate serum levels of trace elements
      (cobalt, copper, zinc, and selenium) and to assess their effects on pregnancy and
      neonatal outcomes. Serum levels of trace elements in 245 Korean pregnant women
      (median gestational age at delivery was 39 + 4 weeks and interquartile range was
      38 + 4-40 + 1 weeks) were compared with those of 527 general adults and those of
      previous studies in other ethnic groups. Pregnancy and neonatal outcomes
      including gestational diabetes, preeclampsia, neonatal birth weight, and
      congenital abnormalities were assessed. The median serum trace element
      concentrations of all pregnant women were: cobalt: 0.39 MUg/L (interquartile
      range, IQR 0.29-0.53), copper: 165.0 MUg/dL (IQR 144.0-187.0), zinc: 57.0 MUg/dL
      (IQR 50.0-64.0), and selenium: 94.0 MUg/L (IQR 87.0-101.0). Serum cobalt and
      copper concentrations were higher in pregnant women than in the general
      population, whereas zinc and selenium levels were lower (p < 0.01).
      Concentrations of all four trace elements varied significantly during the three
      trimesters (p < 0.05), and seasonal variation was found in copper, zinc, and
      selenium, but was not observed for cobalt. The prevalence of preeclampsia was
      significantly lower with high copper (p = 0.03). Trace element levels varied by
      pregnancy trimester and season, and alteration in copper status during pregnancy
      might influence pregnancy outcomes such as preeclampsia.

PMID- 27886086
TI  - Ligustrazine-Oleanolic Acid Glycine Derivative, G-TOA, Selectively Inhibited the
      Proliferation and Induced Apoptosis of Activated HSC-T6 Cells.
AB  - Hepatic fibrosis is a naturally occurring wound-healing reaction, with an
      imbalance of extracellular matrix (ECM) during tissue repair response, which can
      further deteriorate to hepatocellular carcinoma without timely treatment.
      Inhibiting activated hepatic stellate cell (HSC) proliferation and inducing
      apoptosis are the main methods for the treatment of liver fibrosis. In our
      previous study, we found that the TOA-glycine derivative (G-TOA) had exhibited
      more significant inhibitory activity against HepG2 cells and better
      hydrophilicity than TOA, ligustrazine (TMP), and oleanolic acid (OA). However,
      inhibiting activated HSC proliferation and inducing apoptosis by G-TOA had not
      been reported. In this paper, the selective cytotoxicity of G-TOA was evaluated
      on HSC-T6 cells and L02 cells, and apoptosis mechanisms were explored. It was
      found that G-TOA could selectively inhibit the proliferation of activated HSC-T6
      cells, induce morphological changes, early apoptosis, and mitochondrial membrane
      potential depolarization, increase intracellular free calcium levels,
      downregulate the expression of NF-kappaB/p65 and COX-2 protein, and decrease the
      ratio of Bcl-2/Bax, thereby inducing HSC-T6 cell apoptosis. Thence, G-TOA might
      be a potential antifibrosis agent for the therapy of hepatic fibrosis, provided
      that it exerts anti-fibrosis effects on activated HSC-T6 cells.

PMID- 27886087
TI  - State of the Art, Trends and Future of Bluetooth Low Energy, Near Field
      Communication and Visible Light Communication in the Development of Smart Cities.
AB  - The current social impact of new technologies has produced major changes in all
      areas of society, creating the concept of a smart city supported by an electronic
      infrastructure, telecommunications and information technology. This paper
      presents a review of Bluetooth Low Energy (BLE), Near Field Communication (NFC)
      and Visible Light Communication (VLC) and their use and influence within
      different areas of the development of the smart city. The document also presents
      a review of Big Data Solutions for the management of information and the
      extraction of knowledge in an environment where things are connected by an
      "Internet of Things" (IoT) network. Lastly, we present how these technologies can
      be combined together to benefit the development of the smart city.

PMID- 27886084
TI  - Intracranial Thrombus Morphology and Composition Undergoes Time-Dependent Changes
      in Acute Ischemic Stroke: A CT Densitometry Study.
AB  - The aim of our study was to assess whether cerebral artery clots undergo time
      dependent morphological and compositional changes in acute ischemic stroke. We
      performed a retrospective chart review of patients admitted within 5 h from
      symptom onset to three European stroke centers and evaluated non-contrast
      enhanced CT (NECT) for hyperdense artery signs (HAS) in 2565 scans. The occlusion
      site, density of HAS expressed in Hounsfield units (HU), area of HAS, and
      relative density (rHU) (HU clot/HU non-affected artery) were studied and related
      to time from symptom onset, clinical severity, stroke etiology, and laboratory
      parameters. A HAS was present in the middle cerebral artery (MCA) in 185 (7.2%)
      and further explored. The mean time from symptom onset to CT was 100 min (range
      17-300). We found a time-dependent loss of density in the occluded M1 segment
      within the first 5 h (N = 118, 95% CI [-15, -2], p = 0.01). Further, the thrombus
      area in the M2 segment decreased with time (cubic trend N = 67, 95% CI [-63, -8],
      p = 0.02). Overall, and especially in the M2 segment, a lower clot area was
      associated with higher fibrinogen (-21.7%, 95% CI [-34.8, -5.8], p = 0.009). In
      conclusion, our results disclosed time-dependent changes of intracranial thrombi
      with regard to occlusion site, density and area.

PMID- 27886085
TI  - Dirty Money: A Matter of Bacterial Survival, Adherence, and Toxicity.
AB  - In this study we report the underlying reasons to why bacteria are present on
      banknotes and coins. Despite the use of credit cards, mobile phone apps, near
      field-communication systems, and cryptocurrencies such as bitcoins which are
      replacing the use of hard currencies, cash exchanges still make up a significant
      means of exchange for a wide range of purchases. The literature is awash with
      data that highlights that both coins and banknotes are frequently identified as
      fomites for a wide range of microorganisms. However, most of these publications
      fail to provide any insight into the extent to which bacteria adhere and persist
      on money. We treated the various currencies used in this study as microcosms, and
      the bacterial loading from human hands as the corresponding microbiome. We show
      that the substrate from which banknotes are produced have a significant influence
      on both the survival and adherence of bacteria to banknotes. Smooth, polymer
      surfaces provide a poor means of adherence and survival, while coarser and more
      fibrous surfaces provide strong bacterial adherence and an environment to survive
      on. Coins were found to be strongly inhibitory to bacteria with a relatively
      rapid decline in survival on almost all coin surfaces tested. The inhibitory
      influence of coins was demonstrated through the use of antimicrobial disks made
      from coins. Despite the toxic effects of coins on many bacteria, bacteria do have
      the ability to adapt to the presence of coins in their environment which goes
      some way to explain the persistent presence of low levels of bacteria on coins in
      circulation.

PMID- 27886088
TI  - Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA
      Delivery.
AB  - (1) Background: A new family of nanosystems able to discern between normal and
      tumor cells and to release a therapeutic agent in controlled way were synthetized
      by e-beam irradiation. This technique permits to obtain biocompatible, sterile,
      carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels
      (NGs); (2) Methods: Here, we performed a targeting strategy based on the
      recognition of over-expressed proteins on tumor cells, like the folate receptor.
      The selective targeting was demonstrated by co-culture studies and flow cytometry
      analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to
      a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione
      sensitive spacer, in order to obtain a controlled release mechanism, specific for
      cancer cells. The drug efficiency was tested on tumor and healthy cells by flow
      cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity
      assay; the siRNA effect was investigated by RNAi experiment; (3) Results: The
      data obtained showed that the use of NGs permits a faster cargo release in cancer
      cells, in response to high cytosolic glutathione level, also improving their
      efficacy; (4) Conclusion: The possibility of releasing biological molecules in a
      controlled way and to recognize a specific tumor target allows overcoming the
      typical limits of the classic cancer therapy.

PMID- 27886089
TI  - Representation Method for Spectrally Overlapping Signals in Flow Cytometry Based
      on Fluorescence Pulse Time-Delay Estimation.
AB  - Flow cytometry is being applied more extensively because of the outstanding
      advantages of multicolor fluorescence analysis. However, the intensity
      measurement is susceptible to the nonlinearity of the detection method. Moreover,
      in multicolor analysis, it is impossible to discriminate between fluorophores
      that spectrally overlap; this influences the accuracy of the fluorescence pulse
      signal representation. Here, we focus on spectral overlap in two-color analysis,
      and assume that the fluorescence follows the single exponential decay model. We
      overcome these problems by analyzing the influence of the spectral overlap
      quantitatively, which enables us to propose a method of fluorescence pulse signal
      representation based on time-delay estimation (between fluorescence and scattered
      pulse signals). First, the time delays are estimated using a modified chirp Z
      transform (MCZT) algorithm and a fine interpolation of the correlation peak
      (FICP) algorithm. Second, the influence of hardware is removed via calibration,
      in order to acquire the original fluorescence lifetimes. Finally, modulated
      signals containing phase shifts associated with these lifetimes are created
      artificially, using a digital signal processing method, and reference signals are
      introduced in order to eliminate the influence of spectral overlap. Time-delay
      estimation simulation and fluorescence signal representation experiments are
      conducted on fluorescently labeled cells. With taking the potentially overlap of
      autofluorescence as part of the observed fluorescence spectrum, rather than
      distinguishing the individual influence, the results show that the calculated
      lifetimes with spectral overlap can be rectified from 8.28 and 4.86 ns to 8.51
      and 4.63 ns, respectively, using the comprehensive approach presented in this
      work. These values agree well with the lifetimes (8.48 and 4.67 ns) acquired for
      cells stained with single-color fluorochrome. Further, these results indicate
      that the influence of spectral overlap can be eliminated effectively. Moreover,
      modulation, mixing with reference signals, and low-pass filtering are performed
      with a digital signal processing method, thereby obviating the need for a high
      speed analog device and complex circuit system. Finally, the flexibility of the
      comprehensive method presented in this work is significantly higher than that of
      existing methods.

PMID- 27886090
TI  - Radius and Orientation Measurement for Cylindrical Objects by a Light Section
      Sensor.
AB  - In this paper, an efficient method based on a light section sensor is presented
      for measuring cylindrical objects' radii and orientations in a robotic
      application. By this method, the cylindrical objects can be measured under some
      special conditions, such as when the cylindrical objects are welded with others,
      or in the presence of interferences. Firstly, the measurement data are roughly
      identified and accurately screened to effectively recognize ellipses. Secondly,
      the data are smoothed and homogenized to eliminate the effect of laser line loss
      or jump and reduce the influence of the inhomogeneity of measurement data on the
      ellipse fitting to a minimum. Finally, the ellipse fitting is carried out to
      obtain the radii and orientations of the cylindrical objects. Measuring
      experiments and results demonstrate the effective of the proposed radius and
      orientation measurement method for cylindrical object.

PMID- 27886091
TI  - A Testbed to Evaluate the FIWARE-Based IoT Platform in the Domain of Precision
      Agriculture.
AB  - Wireless sensor networks (WSNs) represent one of the most promising technologies
      for precision farming. Over the next few years, a significant increase in the use
      of such systems on commercial farms is expected. WSNs present a number of
      problems, regarding scalability, interoperability, communications, connectivity
      with databases and data processing. Different Internet of Things middleware is
      appearing to overcome these challenges. This paper checks whether one of these
      middleware, FIWARE, is suitable for the development of agricultural applications.
      To the authors' knowledge, there are no works that show how to use FIWARE in
      precision agriculture and study its appropriateness, its scalability and its
      efficiency for this kind of applications. To do this, a testbed has been designed
      and implemented to simulate different deployments and load conditions. The
      testbed is a typical FIWARE application, complete, yet simple and comprehensible
      enough to show the main features and components of FIWARE, as well as the
      complexity of using this technology. Although the testbed has been deployed in a
      laboratory environment, its design is based on the analysis of an Internet of
      Things use case scenario in the domain of precision agriculture.

PMID- 27886092
TI  - 1-Deoxynojirimycin: Occurrence, Extraction, Chemistry, Oral Pharmacokinetics,
      Biological Activities and In Silico Target Fishing.
AB  - 1-Deoxynojirimycin (DNJ, C6H13NO4, 163.17 g/mol), an alkaloid azasugar or
      iminosugar, is a biologically active natural compound that exists in mulberry
      leaves and Commelina communis (dayflower) as well as from several bacterial
      strains such as Bacillus and Streptomyces species. Deoxynojirimycin possesses
      antihyperglycemic, anti-obesity, and antiviral features. Therefore, the aim of
      this detailed review article is to summarize the existing knowledge on
      occurrence, extraction, purification, determination, chemistry, and bioactivities
      of DNJ, so that researchers may use it to explore future perspectives of research
      on DNJ. Moreover, possible molecular targets of DNJ will also be investigated
      using suitable in silico approach.

PMID- 27886094
TI  - Damxungmacin A and B, Two New Amicoumacins with Rare Heterocyclic Cores Isolated
      from Bacillus subtilis XZ-7.
AB  - Two new amicoumacins, named Damxungmacin A (1) and B (2), were isolated from the
      culture broth of a soil-derived bacterium Bacillus subtilis XZ-7. Their chemical
      structures were elucidated by spectroscopic studies (UV, IR, NMR and HR-ESI-MS).
      Compound 1 possessed a 1,4-diazabicyclo[2.2.1]heptane-2-one ring system in its
      structure, which was reported for the first time, while 2 had a 1
      acetylmorpholine-3-one moiety, which was naturally rare. Compound 1 exhibited
      moderate to weak cytotoxic activities against three human tumor cell lines (A549,
      HCT116 and HepG2) with IC50 values of 13.33, 14.34 and 13.64 MUM, respectively.
      Meanwhile, compound 1 showed weak antibacterial activities against some strains
      of Staphylococcus epidermidis, while compound 2 at 16 MUg/mL did not show
      antibacterial activity.

PMID- 27886093
TI  - HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms.
AB  - High mobility group box 1 (HMGB1) is tightly connected to the process of tissue
      organization upon tissue injury. Here we show that HMGB1 controls epithelium and
      connective tissue regeneration both in vivo and in vitro during palatal wound
      healing. Heterozygous HMGB1 (Hmgb1+/-) mice and Wild-type (WT) mice were
      subjected to palatal injury. Maxillary tissues were stained with Mallory Azan or
      immunostained with anti-HMGB1, anti-proliferating cell nuclear antigen (PCNA),
      anti-nuclear factor-kappaB (NF-kappaB) p50 and anti-vascular endothelial growth
      factor (VEGF) antibodies. Palatal gingival explants were cultured with
      recombinant HMGB1 (rHMGB1) co-treated with siRNA targeting receptor for advanced
      glycation end products (RAGEs) for cell migration and PCNA expression analysis.
      Measurement of the wound area showed differences between Hmgb1+/- and WT mice on
      Day 3 after wounding. Mallory Azan staining showed densely packed of collagen
      fibers in WT mice, whereas in Hmgb1+/- mice weave-like pattern of low density
      collagen bundles were present. At three and seven days post-surgery, PCNA, NF
      kappaB p50 and VEGF positive keratinocytes of WT mice were greater than that of
      Hmgb1+/- mice. Knockdown of RAGE prevents the effect of rHMGB1-induced cell
      migration and PCNA expression in gingival cell cultures. The data suggest that
      HMGB1/RAGE axis has crucial roles in palatal wound healing.

PMID- 27886096
TI  - Service Demand Discovery Mechanism for Mobile Social Networks.
AB  - In the last few years, the service demand for wireless data over mobile networks
      has continually been soaring at a rapid pace. Thereinto, in Mobile Social
      Networks (MSNs), users can discover adjacent users for establishing temporary
      local connection and thus sharing already downloaded contents with each other to
      offload the service demand. Due to the partitioned topology, intermittent
      connection and social feature in such a network, the service demand discovery is
      challenging. In particular, the service demand discovery is exploited to identify
      the best relay user through the service registration, service selection and
      service activation. In order to maximize the utilization of limited network
      resources, a hybrid service demand discovery architecture, such as a Virtual
      Dictionary User (VDU) is proposed in this paper. Based on the historical data of
      movement, users can discover their relationships with others. Subsequently,
      according to the users activity, VDU is selected to facilitate the service
      registration procedure. Further, the service information outside of a home
      community can be obtained through the Global Active User (GAU) to support the
      service selection. To provide the Quality of Service (QoS), the Service Providing
      User (SPU) is chosen among multiple candidates. Numerical results show that, when
      compared with other classical service algorithms, the proposed scheme can improve
      the successful service demand discovery ratio by 25% under reduced overheads.

PMID- 27886095
TI  - Sociocultural Determinants of Risky Sexual Behaviors among Adult Latinas: A
      Longitudinal Study of a Community-Based Sample.
AB  - Few studies have examined the sociocultural determinants of risky sexual behavior
      trajectories among adult Latinas. To longitudinally examine the link between
      sociocultural determinants of risky sexual behaviors, we followed a sample of
      adult Latina mother-daughter dyads (n = 267) across a 10-year span through four
      waves of data collection. The present study investigates how risky sexual
      behavior (operationalized as sex under the influence of alcohol or other drugs,
      sex without a condom, or multiple sex partners) is affected by: (a) socioeconomic
      conditions; (b) mental health; (c) medical health; (d) acculturation to U.S.
      culture; (e) interpersonal support; (f) relationship stress; (g) mother-daughter
      attachment; (h) intimate partner violence; (i) religious involvement; and (j)
      criminal justice involvement. Results indicate the following factors are
      negatively associated with risky sexual behavior: drug and alcohol use, treating
      a physical problem with prescription drugs, religious involvement, and mother
      daughter attachment. The following factors are positively associated with risky
      sexual behavior: higher number of mental health symptoms, being U.S.-born, and
      criminal justice involvement. We discuss implications for the future development
      of culturally relevant interventions based on the study findings.

PMID- 27886097
TI  - Investigating Glycol-Split-Heparin-Derived Inhibitors of Heparanase: A Study of
      Synthetic Trisaccharides.
AB  - Heparanase is the only known endoglycosidase able to cleave heparan sulfate.
      Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and
      currently being tested in man as a potential drugs against cancer, contain in
      their structure glycol-split uronic acid moieties probably responsible for their
      strong inhibitory activity. We describe here the total chemical synthesis of the
      trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) and its glycol-split (gs) counterpart
      GlcNS6S-gsGlcA-1,6anGlcNS (2) from glucose. As expected, in a heparanase
      inhibition assay, compound 2 is one order of magnitude more potent than 1. Using
      molecular modeling techniques we have created a 3D model of 1 and 2 that has been
      validated by NOESY NMR experiments. The pure synthetic oligosaccharides have
      allowed the first in depth study of the conformation of a glycol-split glucuronic
      acid. Introducing a glycol-split unit in the structure of 1 increases the
      conformational flexibility and shortens the distance between the two glucosamine
      motives, thus promoting interaction with heparanase. However, comparing the
      relative activities of 2 and roneparstat, we can conclude that the glycol-split
      motive is not the only determinant of the strong inhibitory effect of
      roneparstat.

PMID- 27886098
TI  - Is Green Exercise for All? A Descriptive Study of Green Exercise Habits and
      Promoting Factors in Adult Norwegians.
AB  - Background: Physical activity (PA) in natural environments, known as green
      exercise (GE), can provide health benefits above and beyond PA in other
      environments, but little is known about the extent to which GE is an accessible
      form of weekly PA across different social groups. This study aims to examine the
      "GE phenomenon" in Norway, and evaluate possible differences in GE habits and
      perceived factors that promote GE across sub-groups of this population. Methods:
      2168 adults from all over Norway reported weekly GE and other forms of PA,
      specific forms of GE, and perceived factors that promote GE. Data were examined
      in the overall sample and in relation with the respondents' PA status and
      sociodemographic characteristics. Results: GE, especially "walking in the forest"
      and "activities by/on the sea", was the most popular form of weekly PA, even
      among those with low PA levels. GE was fairly represented across all social
      groups, and especially among the elderly, those who live with spouse/partner and
      those who live in the west regions of Norway, while no associations were found in
      relation to sex, centrality, education level or household income. "Time
      flexibility" and "PA-supportive places" were generally perceived as the most
      important factors that promote GE across all social groups. "Accessibility to
      nature" was generally perceived relatively little important, though a gradient
      was observed in relation to age, education level and household income.
      Conclusions: GE is an important source of weekly PA and health among adult
      Norwegians, especially in sub-groups of interest for public health such as the
      elderly, those with lower socio-economic status and those who live in non-urban
      areas. More should be done to understand and address the inequities relative to
      the perceived accessibility to nature.

PMID- 27886099
TI  - New Insights into the State Trapping of UV-Excited Thymine.
AB  - After UV excitation, gas phase thymine returns to a ground state in 5 to 7 ps,
      showing multiple time constants. There is no consensus on the assignment of these
      processes, with a dispute between models claiming that thymine is trapped either
      in the first (S1) or in the second (S2) excited states. In the present study, a
      nonadiabatic dynamics simulation of thymine is performed on the basis of ADC(2)
      surfaces, to understand the role of dynamic electron correlation on the
      deactivation pathways. The results show that trapping in S2 is strongly reduced
      in comparison to previous simulations considering only non-dynamic electron
      correlation on CASSCF surfaces. The reason for the difference is traced back to
      the energetic cost for formation of a CO pi bond in S2.

PMID- 27886100
TI  - Chemical Constituents of Phaius mishmensis.
AB  - The partitioned n-hexane, CHCl3, and EtOAc extracts from the crude MeOH extract
      of Phaius mishmensis showed considerable cytotoxicities against the human breast
      carcinoma (MCF-7), lung carcinoma (NCI-H460), and central nervous system
      carcinoma (SF-268) cell lines. Four new compounds, phaindole (1), (7'R,8'R)
      phaithrene (2), methyl 3-hydroxy-4,5-dimethoxypropiophenone (3), and methyl
      hematinate (4), as well as 44 known compounds were isolated from the MeOH extract
      of Phaius mishmensis. The structures of the compounds were determined using
      spectroscopic methods.

PMID- 27886101
TI  - Fatty Acid and Phenolic Compound Concentrations in Eight Different Monovarietal
      Virgin Olive Oils from Extremadura and the Relationship with Oxidative Stability.
AB  - Olive oils have been shown to be more resistant to oxidation than other vegetable
      fats, mainly due to their fatty acid (FA) profile which is rich in oleic acid and
      to their high content of antioxidants, principally phenols and tocopherols. This
      has situated virgin olive oils (VOOs) among the fats of high nutritional quality.
      However, it is important to stress that the oil's commercial category (olive oil,
      virgin olive oil, extra-virgin olive oil), the variety of the source plant, and
      the extraction-conservation systems all decisively influence the concentration of
      these antioxidants and the oil's shelf-life. The present work studied the fatty
      acid (FA) and phenolic composition and the oxidative stability (OS) of eight
      olive varieties grown in Extremadura (Arbequina, Cornicabra, Manzanilla Cacerena,
      Manzanilla de Sevilla, Morisca, Pico Limon, Picual, and Verdial de Badajoz), with
      the olives being harvested at different locations and dates. The Cornicabra,
      Picual, and Manzanilla Cacerena VOOs were found to have high oleic acid contents
      (>77.0%), while the VOOs of Morisca and Verdial de Badajoz had high linoleic acid
      contents (>14.5%). Regarding the phenol content, high values were found in the
      Cornicabra (633 mg.kg-1) and Morisca (550 mg.kg-1) VOOs, and low values in
      Arbequina (200 mg.kg-1). The OS was found to depend upon both the variety and the
      date of harvesting. It was higher in the Cornicabra and Picual oils (>55 h), and
      lower in those of Verdial de Badajoz (26.3 h), Arbequina (29.8 h), and Morisca
      (31.5 h). In relating phenols and FAs with the OS, it was observed that, while
      the latter, particularly the linoleic content (R = -0.710, p < 0.001, n = 135),
      constitute the most influential factors, the phenolic compounds, especially o
      diphenols, are equally influential when the oils' linoleic content is >=12.5% (R
      = 0.674, p < 0.001, n = 47). The results show that VOOs' resistance to oxidation
      depends not only on the FA or phenolic profile, but also on the interaction of
      these compounds within the same matrix.

PMID- 27886103
TI  - Groundwater Vulnerability Assessment of the Pingtung Plain in Southern Taiwan.
AB  - In the Pingtung Plain of southern Taiwan, elevated levels of NO3--N in
      groundwater have been reported. Therefore, efforts for assessing groundwater
      vulnerability are required as part of the critical steps to prevent and control
      groundwater pollution. This study makes a groundwater vulnerability assessment
      for the Pingtung Plain using an improved overlay and index-based DRASTIC model.
      The improvement of the DRASTIC model is achieved by reassigning the weighting
      coefficients of the factors in this model with the help of a discriminant
      analysis statistical method. The analytical results obtained from the improved
      DRASTIC model provide a reliable prediction for use in groundwater vulnerability
      assessment to nitrate pollution and can correctly identify the groundwater
      protection zones in the Pingtung Plain. Moreover, the results of the sensitivity
      analysis conducted for the seven parameters in the improved DRASTIC model
      demonstrate that the aquifer media (A) is the most sensitive factor when the
      nitrate-N concentration is below 2.5 mg/L. For the cases where the nitrate-N
      concentration is above 2.5 mg/L, the aquifer media (A) and net recharge (R) are
      the two most important factors.

PMID- 27886102
TI  - An Investigation on the Effect of Extremely Low Frequency Pulsed Electromagnetic
      Fields on Human Electrocardiograms (ECGs).
AB  - For this investigation, we studied the effects of extremely low frequency pulse
      electromagnetic fields (ELF-PEMF) on the human cardiac signal. Electrocardiograms
      (ECGs) of 22 healthy volunteers before and after a short duration of ELF-PEMF
      exposure were recorded. The experiment was conducted under single-blind
      conditions. The root mean square (RMS) value of the recorded data was considered
      as comparison criteria. We also measured and analysed four important ECG time
      intervals before and after ELF-PEMF exposure. Results revealed that the RMS value
      of the ECG recordings from 18 participants (81.8% of the total participants)
      increased with a mean value of 3.72%. The increase in ECG voltage levels was then
      verified by a second experimental protocol with a control exposure. In addition
      to this, we used hyperbolic T-distributions (HTD) in the analysis of ECG signals
      to verify the change in the RR interval. It was found that there were small
      shifts in the frequency-domain signal before and after EMF exposure. This shift
      has an influence on all frequency components of the ECG signals, as all spectrums
      were shifted. It is shown from this investigation that a short time exposure to
      ELF-PEMF can affect the properties of ECG signals. Further study is needed to
      consolidate this finding and discover more on the biological effects of ELF-PEMF
      on human physiological processes.

PMID- 27886106
TI  - Multi-Target Tracking Using an Improved Gaussian Mixture CPHD Filter.
AB  - The cardinalized probability hypothesis density (CPHD) filter is an alternative
      approximation to the full multi-target Bayesian filter for tracking multiple
      targets. However, although the joint propagation of the posterior intensity and
      cardinality distribution in its recursion allows more reliable estimates of the
      target number than the PHD filter, the CPHD filter suffers from the spooky effect
      where there exists arbitrary PHD mass shifting in the presence of missed
      detections. To address this issue in the Gaussian mixture (GM) implementation of
      the CPHD filter, this paper presents an improved GM-CPHD filter, which
      incorporates a weight redistribution scheme into the filtering process to modify
      the updated weights of the Gaussian components when missed detections occur. In
      addition, an efficient gating strategy that can adaptively adjust the gate sizes
      according to the number of missed detections of each Gaussian component is also
      presented to further improve the computational efficiency of the proposed filter.
      Simulation results demonstrate that the proposed method offers favorable
      performance in terms of both estimation accuracy and robustness to clutter and
      detection uncertainty over the existing methods.

PMID- 27886104
TI  - Prevalence and Parental Risk Factors for Speech Disability Associated with Cleft
      Palate in Chinese Children-A National Survey.
AB  - Although the prevalence of oral clefts in China is among the highest worldwide,
      little is known about the prevalence of speech disability associated with cleft
      palate in Chinese children. The data for this study were collected from the
      Second China National Sample Survey on Disability, and identification of speech
      disability associated with cleft palate was based on consensus manuals. Logistic
      regression was used to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs). A weighted number of 112,070 disabled children affected by cleft palate
      were identified, yielding a prevalence of 3.45 per 10,000 children (95% CI: 3.19
      3.71). A history of speech disability in the mother (OR = 20.266, 95% CI 5.788
      70.959, p < 0.0001), older paternal child-bearing age (OR = 1.061, 95% CI 1.017
      1.108, p = 0.0065, per year increase in age), and lower parental education
      (maternal: OR = 3.424, 95% CI 1.082-10.837, p = 0.0363; paternal: OR = 2.923, 95%
      CI 1.245-6.866, p = 0.0138) were strongly associated with risk of speech
      disability associated with cleft palate in the offspring. Our results showed that
      maternal speech disability, older paternal child-bearing age, and lower levels of
      parental education were independent risk factors for speech disability associated
      with cleft palate for children in China. These findings may have important
      implications for health disparities and prevention.

PMID- 27886107
TI  - Evaluation Research of the Effects of Longitudinal Speed Reduction Markings on
      Driving Behavior: A Driving Simulator Study.
AB  - The objective of this paper is to explore the effects of longitudinal speed
      reduction markings (LSRMs) on vehicle maneuvering and drivers' operation
      performance on interchange connectors with different radii. Empirical data were
      collected in a driving simulator. Indicators-relative speed change, standard
      deviation of acceleration, and gas/brake pedal power-were proposed to
      characterize driving behavior. Statistical results revealed that LSRMs could
      reduce vehicles' travel speed and limit drivers' willingness to increase speed in
      the entire connector. To probe the impacts of LSRMs, the connecter was split into
      four even sections. Effects of LSRMs on driving behavior were stronger in the
      second and the final sections of connectors. LSRMs also enhanced drivers'
      adaptability in the first three quarters of a connector when the radius was 50 m.
      Drivers' gas pedal operation would be impacted by LSRMs in the entire connector
      when the radius was 50 m. LSRMs could only make drivers press brake pedal more
      frequently in the second section with 80 m and 100 m radius. In the second
      quarter section of a connector-from the FQP (the first quartile point) to the MC
      (the middle point of curve)-LSRMs have better effects on influencing vehicle
      maneuvering and drivers' operation performance.

PMID- 27886108
TI  - Chemoenzymatic Synthesis of trans-beta-Aryl-delta-hydroxy-gamma-lactones and
      Enzymatic Kinetic Resolution of Their Racemic Mixtures.
AB  - Two novel and convenient routes to obtain enantiomerically enriched trans-beta
      aryl-delta-hydroxy-gamma-lactones 5a-d with potential antifeedant and anticancer
      activity were developed. In the first method starting from corresponding
      enantiomers of gamma,delta-unsaturated esters 4a-d derived from enzymatically
      resolved allyl alcohols 1a-d, both enantiomers of hydroxylactones 5a-d were
      synthesized with high enantiomeric excesses (73%-97%). Configurations of the
      stereogenic centers of the synthesized compounds were assigned based on the
      mechanism of acidic lactonization of esters 4a-d in the presence of m
      chloroperbenzoic acid (m-CPBA). An alternative method for the production of
      optically active trans-beta-aryl-delta-hydroxy-gamma-lactones 5a-d was lipase
      catalyzed kinetic resolution of their racemic mixtures by transesterification
      with vinyl propionate as the acyl donor. The most efficient enzyme in the
      screening procedure was lipase B from Candida antarctica. Its application on a
      preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones 5a
      d and (+)-(4R,5S,6R)-propionates 6a-d, most of them with high enantiomeric
      excesses (92%-98%). Resolution of lactone 5d with bulky 1,3-benzodioxol ring
      provided products with significantly lower optical purity (ee = 89% and 84% for
      hydroxylactone 5d and propionate 6d, respectively). The elaborated methods give
      access to both enantiomers of trans-beta-aryl-delta-hydroxy-gamma-lactones 5a-d
      with the defined absolute configurations of stereogenic centers, which is crucial
      requirement for the investigations of relationship: spatial structure-biological
      activity.

PMID- 27886109
TI  - Influence of Secondary-Structure Folding on the Mutually Exclusive Folding
      Process of GL5/I27 Protein: Evidence from Molecular Dynamics Simulations.
AB  - Mutually exclusive folding proteins are a class of multidomain proteins in which
      the host domain remains folded while the guest domain is unfolded, and both
      domains achieve exchange of their folding status by a mutual exclusive folding
      (MEF) process. We carried out conventional and targeted molecular dynamics
      simulations for the mutually exclusive folding protein of GL5/I27 to address the
      MEF transition mechanisms. We constructed two starting models and two targeted
      models, i.e., the starting models GL5/I27-S and GL5/I27-ST in which the first
      model involves the host domain GL5 and the secondary-structure unfolded guest
      domain I27-S, while the second model involves the host domain GL5 and the
      secondary/tertiary-structure extending guest domain I27-ST, and the target models
      GL5-S/I27 and GL5-ST/I27 in which GL5-S and GL5-ST represent the secondary
      structure unfolding and the secondary/tertiary-structure extending, respectively.
      We investigated four MEF transition processes from both starting models to both
      target models. Based on structural changes and the variations of the radius of
      gyration (Rg) and the fractions of native contacts (Q), the formation of the
      secondary structure of the I27-guest domain induces significant extending of the
      GL5-host domain; but the primary shrinking of the tertiary structure of the I27
      guest domain causes insignificant extending of the GL5-host domain during the
      processes. The results indicate that only formation of the secondary structure in
      the I27-guest domain provides the main driving force for the mutually exclusive
      folding/unfolding between the I27-guest and GL5-host domains. A special structure
      as an intermediate with both host and guest domains being folded at the same time
      was found, which was suggested by the experiment. The analysis of hydrogen bonds
      and correlation motions supported the studied transition mechanism with the
      dynamical "tug-of-war" phenomenon.

PMID- 27886110
TI  - Effects of Scale, Question Location, Order of Response Alternatives, and Season
      on Self-Reported Noise Annoyance Using ICBEN Scales: A Field Experiment.
AB  - The type of noise annoyance scale and aspects of its presentation such as
      response format or location within a questionnaire and other contextual factors
      may affect self-reported noise annoyance. By means of a balanced experimental
      design, the effect of type of annoyance question and corresponding scale (5-point
      verbal vs. 11-point numerical ICBEN (International Commission on Biological
      Effects of Noise) scale), presentation order of scale points (ascending vs.
      descending), question location (early vs. late within the questionnaire), and
      survey season (autumn vs. spring) on reported road traffic noise annoyance was
      investigated in a postal survey with a stratified random sample of 2386 Swiss
      residents. Our results showed that early appearance of annoyance questions was
      significantly associated with higher annoyance scores. Questionnaires filled out
      in autumn were associated with a significantly higher annoyance rating than in
      the springtime. No effect was found for the order of response alternatives.
      Standardized average annoyance scores were slightly higher using the 11-point
      numerical scale whereas the percentage of highly annoyed respondents was higher
      based on the 5-point scale, using common cutoff points. In conclusion, placement
      and presentation of annoyance questions within a questionnaire, as well as the
      time of the year a survey is carried out, have small but demonstrable effects on
      the degree of self-reported noise annoyance.

PMID- 27886112
TI  - Synthesis, Characterization, and Anti-Inflammatory Activities of Methyl
      Salicylate Derivatives Bearing Piperazine Moiety.
AB  - In this study, a new series of 16 methyl salicylate derivatives bearing a
      piperazine moiety were synthesized and characterized. The in vivo anti
      inflammatory activities of target compounds were investigated against xylol
      induced ear edema and carrageenan-induced paw edema in mice. The results showed
      that all synthesized compounds exhibited potent anti-inflammatory activities.
      Especially, the anti-inflammatory activities of compounds M15 and M16 were higher
      than that of aspirin and even equal to that of indomethacin at the same dose. In
      addition, the in vitro cytotoxicity activities and anti-inflammatory activities
      of four target compounds were performed in RAW264.7 macrophages, and compound M16
      was found to significantly inhibit the release of lipopolysaccharide (LPS)
      induced interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in a dose
      dependent manner. In addition, compound M16 was found to attenuate LPS induced
      cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide
      information for the development of new and safe anti-inflammatory agents.

PMID- 27886105
TI  - Pro-Tumoral Inflammatory Myeloid Cells as Emerging Therapeutic Targets.
AB  - Since the observation of Virchow, it has long been known that the tumor
      microenvironment constitutes the soil for the infiltration of inflammatory cells
      and for the release of inflammatory mediators. Under certain circumstances,
      inflammation remains unresolved and promotes cancer development. Here, we review
      some of these indisputable experimental and clinical evidences of cancer related
      smouldering inflammation. The most common myeloid infiltrate in solid tumors is
      composed of myeloid-derived suppressor cells (MDSCs) and tumor-associated
      macrophages (TAMs). These cells promote tumor growth by several mechanisms,
      including their inherent immunosuppressive activity, promotion of
      neoangiogenesis, mediation of epithelial-mesenchymal transition and alteration of
      cellular metabolism. The pro-tumoral functions of TAMs and MDSCs are further
      enhanced by their cross-talk offering a myriad of potential anti-cancer
      therapeutic targets. We highlight these main pro-tumoral mechanisms of myeloid
      cells and give a general overview of their phenotypical and functional diversity,
      offering examples of possible therapeutic targets. Pharmacological targeting of
      inflammatory cells and molecular mediators may result in therapies improving
      patient condition and prognosis. Here, we review experimental and clinical
      findings on cancer-related inflammation with a major focus on creating an
      inventory of current small molecule-based therapeutic interventions targeting
      cancer-related inflammatory cells: TAMs and MDSCs.

PMID- 27886111
TI  - Effects of Fetal Exposure to Asian Sand Dust on Development and Reproduction in
      Male Offspring.
AB  - In recent experimental studies, we reported the aggravating effects of Asian sand
      dust (ASD) on male reproduction in mice. However, the effects of fetal ASD
      exposure on male reproduction have not been investigated. The present study
      investigated the effects of fetal ASD exposure on reproduction in male offspring.
      Using pregnant CD-1 mice, ASD was administered intratracheally on days 7 and 14
      of gestation, and the reproduction of male offspring was determined at 5, 10, and
      15 weeks after birth. The secondary sex ratio was significantly lower in the
      fetal ASD-exposed mice than in the controls. Histologic examination showed
      partial vacuolation of seminiferous tubules in immature mice. Moreover, daily
      sperm production (DSP) was significantly less in the fetal ASD-exposed mice than
      in the controls. DSP in the fetal ASD-exposed mice was approximately 10% less
      than the controls at both 5 and 10 weeks. However, both the histologic changes
      and the DSP decrease were reversed as the mice matured. These findings suggest
      that ASD exposure affects both the fetal development and the reproduction of male
      offspring. In the future, it will be necessary to clarify the onset mechanisms of
      ASD-induced male fetus death and male reproductive disorders.

PMID- 27886114
TI  - AutoDock-GIST: Incorporating Thermodynamics of Active-Site Water into Scoring
      Function for Accurate Protein-Ligand Docking.
AB  - Water plays a significant role in the binding process between protein and ligand.
      However, the thermodynamics of water molecules are often underestimated, or even
      ignored, in protein-ligand docking. Usually, the free energies of active-site
      water molecules are substantially different from those of waters in the bulk
      region. The binding of a ligand to a protein causes a displacement of these
      waters from an active site to bulk, and this displacement process substantially
      contributes to the free energy change of protein-ligand binding. The free energy
      of active-site water molecules can be calculated by grid inhomogeneous solvation
      theory (GIST), using molecular dynamics (MD) and the trajectory of a target
      protein and water molecules. Here, we show a case study of the combination of
      GIST and a docking program and discuss the effectiveness of the displacing gain
      of unfavorable water in protein-ligand docking. We combined the GIST-based
      desolvation function with the scoring function of AutoDock4, which is called
      AutoDock-GIST. The proposed scoring function was assessed employing 51 ligands of
      coagulation factor Xa (FXa), and results showed that both scoring accuracy and
      docking success rate were improved. We also evaluated virtual screening
      performance of AutoDock-GIST using FXa ligands in the directory of useful decoys
      enhanced (DUD-E), thus finding that the displacing gain of unfavorable water is
      effective for a successful docking campaign.

PMID- 27886113
TI  - Predictors of Urinary 3-Phenoxybenzoic Acid Levels in 50 North Carolina Adults.
AB  - Limited data are available on the non-chemical stressors that impact adult
      exposures to pyrethroid insecticides based on urinary biomonitoring. The urinary
      metabolite, 3-phenoxybenzoic acid (3-PBA), is commonly used to assess human
      exposure to a number of pyrethroids. In a further analysis of published study
      data, we quantified urinary 3-PBA levels of 50 adults over a single, 24-h
      sampling period and examined the associations between the biomarker measurements
      and selected non-chemical stressors (demographic, lifestyle, and dietary
      factors). A convenience sample of 50 adults was recruited in North Carolina in
      2009-2011. Participants collected individual urine voids (up to 11) and filled
      out activity, food, and pesticide use diaries over a 24-h sampling period. Urine
      voids (n = 326) were analyzed for 3-PBA concentrations using high-performance
      liquid chromatography-tandem mass spectrometry. 3-PBA was detected in 98% of the
      24-h composited urine samples. The geometric mean urinary 3-PBA level was 1.68
      ng/mL in adults. Time spent outside (p = 0.0006) was a highly significant
      predictor of natural log-transformed (ln) urinary 3-PBA levels, while consumption
      of coffee (p = 0.007) and breads (p = 0.019) and ln creatinine levels (p = 0.037)
      were significant predictors of urinary 3-PBA levels. In conclusion, we identified
      specific factors that substantially increased adult exposures to pyrethroids in
      their everyday environments.

PMID- 27886115
TI  - The Draft Genome Sequence of Actinokineospora bangkokensis 44EHWT Reveals the
      Biosynthetic Pathway of the Antifungal Thailandin Compounds with Unusual
      Butylmalonyl-CoA Extender Units.
AB  - We report the draft genome sequence of Actinokineospora bangkokensis 44EHWT, the
      producer of the antifungal polyene compounds, thailandins A and B. The sequence
      contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the
      biosynthesis of secondary metabolites. There are three gene clusters encoding
      large polyketide synthases of type I. Annotation of the ORF functions and
      targeted gene disruption enabled us to identify the cluster for thailandin
      biosynthesis. We propose a plausible biosynthetic pathway for thailandin, where
      the unusual butylmalonyl-CoA extender unit is incorporated and results in an
      untypical side chain.

PMID- 27886116
TI  - Simultaneous Ultra Performance Liquid Chromatography Determination and
      Antioxidant Activity of Linarin, Luteolin, Chlorogenic Acid and Apigenin in
      Different Parts of Compositae Species.
AB  - Linarin (LA), luteolin (LE), chlorogenic acid (CA) and apigenin (AP) are four
      major flavonoids with various promising bioactivities found in Compositae (COP)
      species. A reliable, reproducible and accurate method for the simultaneous and
      quantitative determination of these four major flavonoids by Ultra Performance
      Liquid Chromatography (UPLC) analysis was developed. This method should be
      appropriate for the quality assurance of COP. The UPLC separation was carried out
      using an octadecylsilane (ODS) Hypersil (2.1 mm * 250 mm, 1.9 MUm) and a mobile
      phase composed of acetonitrile and 0.1% formic acid in water at a flow rate 0.44
      mL/min and ultraviolet (UV) detection 254 nm. Gradient elution was employed. The
      method was precise, with relative standard deviation below 3.0% and showed
      excellent linearity (R2 > 0.999). The recoveries for the four flavonoids in COP
      were between 95.49%-106.23%. The average contents of LA, LE, CA and AP in
      different parts (flower, leave and stem) of COP were between 0.64-1.47 g/100 g,
      0.66-0.89 g/100 g, 0.32-0.52 g/100 g and 0.16-0.18 g/100 g, respectively. The
      method was accurate and reproducible and it can provide a quantitative basis for
      quality control of COP.

PMID- 27886117
TI  - Surface Modification of a Nanoporous Carbon Photoanode upon Irradiation.
AB  - The photocorrosion of a nanoporous carbon photoanode, with low surface
      functionalization and high performance towards the photoelectrochemical oxidation
      of water using simulated solar light, was investigated. Two different light
      configurations were used to isolate the effect of the irradiation wavelength (UV
      and visible light) on the textural and chemical features of the carbon
      photoanode, and its long-term photocatalytic performance for the oxygen evolution
      reaction. A complete characterization of the carbon showed that the
      photocorrosion of carbon anodes of low functionalization follows a different
      pathway than highly functionalized carbons. The carbon matrix gets slightly
      oxidized, with the formation of carboxylic and carbonyl-like moieties in the
      surface of the carbon anode after light exposure. The oxidation of the carbon
      occurred due to the photogeneration of oxygen reactive species upon the
      decomposition of water during the irradiation of the photoanodes. Furthermore,
      the photoinduced surface reactions depend on the nature of the carbon anode and
      its ability to photogenerate reactive species in solution, rather than on the
      wavelength of the irradiation source. This surface modification is responsible
      for the decreased efficiency of the carbon photoanode throughout long
      illumination periods, due to the effect of the oxidation of the carbon matrix on
      the charge transfer. In this work, we have corroborated that, in the case of a
      low functionalization carbon material, the photocorrosion also occurs although it
      proceeds through a different pathway. The carbon anode gets gradually slightly
      oxidized due to the photogeneration of O-reactive species, being the
      incorporation of the O-groups responsible for the decreased performance of the
      anode upon long-term irradiation due to the effect of the oxidation of the carbon
      matrix on the electron transfer.

PMID- 27886118
TI  - Natural Compound Histone Deacetylase Inhibitors (HDACi): Synergy with
      Inflammatory Signaling Pathway Modulators and Clinical Applications in Cancer.
AB  - The remarkable complexity of cancer involving multiple mechanisms of action and
      specific organs led researchers Hanahan and Weinberg to distinguish biological
      capabilities acquired by cancer cells during the multistep development of human
      tumors to simplify its understanding. These characteristic hallmarks include the
      abilities to sustain proliferative signaling, evade growth suppressors, resist
      cell death, enable replicative immortality, induce angiogenesis, activate
      invasion and metastasis, avoid immune destruction, and deregulate cellular
      energetics. Furthermore, two important characteristics of tumor cells that
      facilitate the acquisition of emerging hallmarks are tumor-promoting inflammation
      and genome instability. To treat a multifactorial disease such as cancer, a
      combination treatment strategy seems to be the best approach. Here we focus on
      natural histone deacetylase inhibitors (HDACi), their clinical uses as well as
      synergies with modulators of the pro-inflammatory transcription factor signaling
      pathways.

PMID- 27886119
TI  - Synthesis and Antifungal Screening of 2-{[1-(5-Alkyl/arylalkylpyrazin-2
      yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones.
AB  - Two novel thiosemicarbazones and eight novel 2-{[1-(5-alkyl/arylalkylpyrazin-2
      yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones were prepared and tested against
      a panel of eight fungal strains-Candida albicans ATCC 44859, Candida tropicalis
      156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188,
      Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton
      interdigitale 445. 1,3-Thiazolidin-4-ones exhibited activity against all strains,
      the most potent derivative was 2-{[1-(5-butylpyrazin-2-yl)ethylidene]hydrazono}e
      1,3-thiazolidin-4-one. Susceptibility of C. glabrata to the studied 1,3
      thiazolidin-4-ones (minimum inhibitory concentrations (MICs) were in the range
      0.57 to 2.78 mg/L) is of great interest as this opportunistic pathogen is poorly
      susceptible to azoles and becomes resistant to echinocandins. Antifungal potency
      of thiosemicarbazones was slightly lower than that of 1,3-thiazolidin-4-ones.

PMID- 27886120
TI  - The Role and Application of Sirtuins and mTOR Signaling in the Control of Ovarian
      Functions.
AB  - The present short review demonstrates the involvement of sirtuins (SIRTs) in the
      control of ovarian functions at various regulatory levels. External and endocrine
      factors can affect female reproduction via SIRTs-mammalian target of rapamycin
      (mTOR) system, which, via hormones and growth factors, can in turn regulate basic
      ovarian functions (proliferation, apoptosis, secretory activity of ovarian cells,
      their response to upstream hormonal regulators, ovarian folliculo- and oogenesis,
      and fecundity). SIRTs and SIRTs-related signaling molecules and drugs regulating
      mTOR can be used for characterization, prediction, and regulation of ovarian
      functions, as well as for diagnostics and treatment of ovarian disorders.

PMID- 27886121
TI  - Sodium Butyrate Reduces Colitogenic Immunoglobulin A-Coated Bacteria and Modifies
      the Composition of Microbiota in IL-10 Deficient Mice.
AB  - High levels of immunoglobulin A (IgA)-coated bacteria may have a role in driving
      inflammatory bowel disease (IBD). We therefore investigated the effect of sodium
      butyrate on microbiota in IBD prone interleukin (IL)-10-/- mice. At 8 weeks of
      age, mice were allocated into three groups (n = 4/group): normal (C57BL/6), IL-10
      /-, and IL-10-/- treated with sodium butyrate (100 mM). Severity of colitis,
      inflammatory cytokine and short-chain fatty acid (SCFA) concentration in proximal
      colon contents, the percentage of IgA-coated bacteria and microbiota composition
      by 16S ribosomal RNA assessment of stool were measured after 4 weeks of
      treatment. Sodium butyrate ameliorated histological colitis and decreased levels
      of tumor necrosis factor (TNF)-alpha and IL-6 in IL-10-/- mice compared with
      those without treatment. At the phylum level, a reduction in Bacteroidetes and an
      increase in Firmicutes in IL-10-/- mice treated with sodium butyrate were
      observed. Additionally, Prevotellaceae species were reduced in IL-10-/- mice
      treated with sodium butyrate as compared with those without treatment. The level
      of biodiversity was slightly increased and the amount of IgA-coated bacteria
      decreased in IL-10-/- mice treated with sodium butyrate compared with those
      without treatment. Our results indicate that sodium butyrate protects against
      colitis, possibly through modifying the gut microbiota, enriching biodiversity
      and reducing the amount of colitogenic IgA-coated bacteria in IL-10-/- mice.

PMID- 27886122
TI  - Remote Blood Glucose Monitoring in mHealth Scenarios: A Review.
AB  - Glucose concentration in the blood stream is a critical vital parameter and an
      effective monitoring of this quantity is crucial for diabetes treatment and
      intensive care management. Effective bio-sensing technology and advanced signal
      processing are therefore of unquestioned importance for blood glucose monitoring.
      Nevertheless, collecting measurements only represents part of the process as
      another critical task involves delivering the collected measures to the treating
      specialists and caregivers. These include the clinical staff, the patient's
      significant other, his/her family members, and many other actors helping with the
      patient treatment that may be located far away from him/her. In all of these
      cases, a remote monitoring system, in charge of delivering the relevant
      information to the right player, becomes an important part of the sensing
      architecture. In this paper, we review how the remote monitoring architectures
      have evolved over time, paralleling the progress in the Information and
      Communication Technologies, and describe our experiences with the design of
      telemedicine systems for blood glucose monitoring in three medical applications.
      The paper ends summarizing the lessons learned through the experiences of the
      authors and discussing the challenges arising from a large-scale integration of
      sensors and actuators.

PMID- 27886123
TI  - One-Pot Click Access to a Cyclodextrin Dimer-Based Novel Aggregation Induced
      Emission Sensor and Monomer-Based Chiral Stationary Phase.
AB  - A 'two birds, one stone' strategy was developed via a one-pot click reaction to
      simultaneously prepare a novel cyclodextrin (CD) dimer based aggregation induced
      emission (AIE) sensor (AIE-DCD) and a monomer based chiral stationary phase (CSP
      MCD) for chiral high performance liquid chromatography (CHPLC). AIE-DCD was found
      to afford satisfactory AIE response for specific detection of Zn2+ with a
      detection limit of 50 nM. CSP-MCD exhibits excellent enantioseparation ability
      toward dansyl amino acids, where the resolution of dansyl amino leucine reaches
      5.43.

PMID- 27886125
TI  - Thermal-Performance Instability in Piezoresistive Sensors: Inducement and
      Improvement.
AB  - The field of piezoresistive sensors has been undergoing a significant revolution
      in terms of design methodology, material technology and micromachining process.
      However, the temperature dependence of sensor characteristics remains a hurdle to
      cross. This review focuses on the issues in thermal-performance instability of
      piezoresistive sensors. Based on the operation fundamental, inducements to the
      instability are investigated in detail and correspondingly available ameliorative
      methods are presented. Pros and cons of each improvement approach are also
      summarized. Though several schemes have been proposed and put into reality with
      favorable achievements, the schemes featuring simple implementation and excellent
      compatibility with existing techniques are still emergently demanded to construct
      a piezoresistive sensor with excellent comprehensive performance.

PMID- 27886124
TI  - Advances in Cancer Immunotherapy in Solid Tumors.
AB  - Immunotherapy is heralded as one of the most important advances in oncology.
      Until recently, only limited immunotherapeutic options were available in selected
      immunogenic cancers like melanoma and renal cell carcinomas. Nowadays, there is
      an improved understanding that anti-tumor immunity is controlled by a delicate
      balance in the tumor microenvironment between immune stimulatory and immune
      inhibitory pathways. Either by blocking the inhibitory pathways or stimulating
      the activating pathways that regulate cytotoxic lymphocytes, anti-tumor immunity
      can be enhanced leading to durable anti-tumor responses. Drugs which block the
      immune regulatory checkpoints namely the PD-1/PDL1 and CTLA 4 pathway have shown
      tremendous promise in a wide spectrum of solid and hematological malignancies,
      significantly improving overall survival in newly diagnosed and heavily
      pretreated patients alike. Hence there is renewed enthusiasm in the field of
      immune oncology with current research focused on augmenting responses to
      checkpoint inhibitors by combination therapy as well as studies looking at other
      immune modulators and adoptive T cell therapy. In this article, we highlight the
      key clinical advances and concepts in immunotherapy with particular emphasis on
      checkpoint inhibition as well as the future direction in this field.

PMID- 27886126
TI  - Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of
      Autoimmune Neurological Diseases: Insights from Preclinical Studies.
AB  - Exaggerated or inappropriate responses by B cells are an important feature in
      many types of autoimmune neurological diseases. The recent success of B-cell
      depletion in the treatment of multiple sclerosis (MS) has stimulated the
      development of novel B-cell-targeting therapies with the potential for improved
      efficacy. CD19 has emerged as a promising target for the depletion of B cells as
      well as CD19-positive plasmablasts and plasma cells. Inebilizumab (MEDI-551), an
      anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity
      against B cells, is currently being evaluated in MS and neuromyelitis optica.
      This review discusses the role of B cells in autoimmune neurological disorders,
      summarizes the development of inebilizumab, and analyzes the recent results for
      inebilizumab treatment in an autoimmune encephalitis mouse model. The novel
      insights obtained from these preclinical studies can potentially guide future
      investigation of inebilizumab in patients.

PMID- 27886127
TI  - Viperid Envenomation Wound Exudate Contributes to Increased Vascular Permeability
      via a DAMPs/TLR-4 Mediated Pathway.
AB  - Viperid snakebite envenomation is characterized by inflammatory events including
      increase in vascular permeability. A copious exudate is generated in tissue
      injected with venom, whose proteomics analysis has provided insights into the
      mechanisms of venom-induced tissue damage. Hereby it is reported that wound
      exudate itself has the ability to induce increase in vascular permeability in the
      skin of mice. Proteomics analysis of exudate revealed the presence of cytokines
      and chemokines, together with abundant damage associated molecular pattern
      molecules (DAMPs) resulting from both proteolysis of extracellular matrix and
      cellular lysis. Moreover, significant differences in the amounts of
      cytokines/chemokines and DAMPs were detected between exudates collected 1 h and
      24 h after envenomation, thus highlighting a complex temporal dynamic in the
      composition of exudate. Pretreatment of mice with Eritoran, an antagonist of Toll
      like receptor 4 (TLR4), significantly reduced the exudate-induced increase in
      vascular permeability, thus suggesting that DAMPs might be acting through this
      receptor. It is hypothesized that an "Envenomation-induced DAMPs cycle of tissue
      damage" may be operating in viperid snakebite envenomation through which venom
      induced tissue damage generates a variety of DAMPs which may further expand
      tissue alterations.

PMID- 27886128
TI  - Worldwide Mycotoxins Exposure in Pig and Poultry Feed Formulations.
AB  - The purpose of this review is to present information about raw materials that can
      be used in pig and poultry diets and the factors responsible for variations in
      their mycotoxin contents. The levels of mycotoxins in pig and poultry feeds are
      calculated based on mycotoxin contamination levels of the raw materials with
      different diet formulations, to highlight the important role the stage of
      production and the raw materials used can have on mycotoxins levels in diets. Our
      analysis focuses on mycotoxins for which maximum tolerated levels or regulatory
      guidelines exist, and for which sufficient contamination data are available. Raw
      materials used in feed formulation vary considerably depending on the species of
      animal, and the stage of production. Mycotoxins are secondary fungal metabolites
      whose frequency and levels also vary considerably depending on the raw materials
      used and on the geographic location where they were produced. Although several
      reviews of existing data and of the literature on worldwide mycotoxin
      contamination of food and feed are available, the impact of the different raw
      materials used on feed formulation has not been widely studied.

PMID- 27886129
TI  - Insights into the Hypertensive Effects of Tityus serrulatus Scorpion Venom:
      Purification of an Angiotensin-Converting Enzyme-Like Peptidase.
AB  - The number of cases of envenomation by scorpions has grown significantly in
      Brazil since 2007, with the most severe cases being caused by the Tityus
      serrulatus scorpion. Although envenomed patients mostly suffer neurotoxic
      manifestations, other symptoms, such as hypertension, cannot be exclusively
      attributed to neurotoxins. Omics analyses have detected plentiful amounts of
      metalloproteases in T. serrulatus venom. However, the roles played by these
      enzymes in envenomation are still unclear. Endeavoring to investigate the
      functions of scorpion venom proteases, we describe here for the first time an
      Angiotensin I-Converting Enzyme-like peptidase (ACE-like) purified from T.
      serrulatus venom. The crude venom cleaved natural and fluorescent substrates and
      these activities were inhibited by captopril. Regarding the serum neutralization,
      the scorpion antivenom was more effective at blocking the ACE-like activity than
      arachnid antivenom, although neither completely inhibited the venom cleavage
      action, even at higher doses. ACE-like was purified from the venom after three
      chromatographic steps and its identity was confirmed by mass spectrometric and
      transcriptomic analyses. Bioinformatics analysis showed homology between the ACE
      like transcript sequences from Tityus spp. and human testis ACE. These findings
      advance our understanding of T. serrulatus venom components and may improve
      treatment of envenomation victims, as ACE-like may contribute to envenomation
      symptoms, especially the resulting hypertension.

PMID- 27886130
TI  - Emotion-Bracelet: A Web Service for Expressing Emotions through an Electronic
      Interface.
AB  - The mechanisms to communicate emotions have dramatically changed in the last 10
      years with social networks, where users massively communicate their emotional
      states by using the Internet. However, people with socialization problems have
      difficulty expressing their emotions verbally or interpreting the environment and
      providing an appropriate emotional response. In this paper, a novel solution
      called the Emotion-Bracelet is presented that combines a hardware device and a
      software system. The proposed approach identifies the polarity and emotional
      intensity of texts published on a social network site by performing real-time
      processing using a web service. It also shows emotions with a LED matrix using
      five emoticons that represent positive, very positive, negative, very negative,
      and neutral states. The Emotion-Bracelet is designed to help people express their
      emotions in a non-intrusive way, thereby expanding the social aspect of human
      emotions.

PMID- 27886131
TI  - Changes in Meat/Poultry/Fish Consumption in Australia: From 1995 to 2011-2012.
AB  - The purpose of the study was to examine temporal changes in meat/poultry/fish
      consumption patterns between 1995 and 2011-2012 in the Australian population.
      Meat/poultry/fish consumption from all food sources, including recipes, was
      analysed by gender, age group, and socio-economic status using 24-h recall data
      from the 1995 National Nutrition Survey (n = 13,858) and the 2011-2012 National
      Nutrition and Physical Activity Survey (n = 12,153). The overall proportion of
      people consuming meat/poultry/fish remained stable (91.7% versus 91.3%, p =
      0.55), but a shift in the type of meat consumed was observed. Red meat, including
      beef and lamb, was consumed by fewer people over the time period (from 56% to
      49%), whereas poultry consumption increased (from 29% to 38%). Amounts of all
      meat/poultry/fish consumed were reportedly higher in 2011-2012 compared with
      1995. This resulted in similar (red meat, and processed meat) or slightly higher
      (poultry, and fish) per-capita intakes in 2011-2012. The magnitude of change of
      consumption varied between children and adults, and by gender. Monitoring trends
      in consumption is particularly relevant to policy makers, researchers and other
      health professionals for the formulation of dietary recommendations and
      estimation of potential health outcomes.

PMID- 27886132
TI  - The Future is The Past: Methylation QTLs in Schizophrenia.
AB  - Genome-wide association studies (GWAS) have remarkably advanced insight into the
      genetic basis of schizophrenia (SCZ). Still, most of the functional variance in
      disease risk remains unexplained. Hence, there is a growing need to map genetic
      variability-to-genes-to-functions for understanding the pathophysiology of SCZ
      and the development of better treatments. Genetic variation can regulate various
      cellular functions including DNA methylation, an epigenetic mark with important
      roles in transcription and the mediation of environmental influences. Methylation
      quantitative trait loci (meQTLs) are derived by mapping levels of DNA methylation
      in genetically different, genotyped individuals and define loci at which DNA
      methylation is influenced by genetic variation. Recent evidence points to an
      abundance of meQTLs in brain tissues whose functional contributions to
      development and mental diseases are still poorly understood. Interestingly, fetal
      meQTLs reside in regulatory domains affecting methylome reconfiguration during
      early brain development and are enriched in loci identified by GWAS for SCZ.
      Moreover, fetal meQTLs are preserved in the adult brain and could trace early
      epigenomic deregulation during vulnerable periods. Overall, these findings
      highlight the role of fetal meQTLs in the genetic risk for and in the possible
      neurodevelopmental origin of SCZ.

PMID- 27886133
TI  - Epigenetic Impact on EBV Associated B-Cell Lymphomagenesis.
AB  - Epigenetic modifications leading to either transcriptional repression or
      activation, play an indispensable role in the development of human cancers.
      Epidemiological study revealed that approximately 20% of all human cancers are
      associated with tumor viruses. Epstein-Barr virus (EBV), the first human tumor
      virus, demonstrates frequent epigenetic alterations on both viral and host
      genomes in associated cancers-both of epithelial and lymphoid origin. The cell
      type-dependent different EBV latent gene expression patterns appear to be
      determined by the cellular epigenetic machinery and similarly viral oncoproteins
      recruit epigenetic regulators in order to deregulate the cellular gene expression
      profile resulting in several human cancers. This review elucidates the epigenetic
      consequences of EBV-host interactions during development of multiple EBV-induced
      B-cell lymphomas, which may lead to the discovery of novel therapeutic
      interventions against EBV-associated B-cell lymphomas by alteration of reversible
      patho-epigenetic markings.

PMID- 27886134
TI  - Priority Actions and Progress to Substantially and Sustainably Reduce the
      Mortality, Morbidity and Socioeconomic Burden of Tropical Snakebite.
AB  - The deliberations and conclusions of a Hinxton Retreat convened in September
      2015, entitled "Mechanisms to reverse the public health neglect of snakebite
      victims" are reported. The participants recommended that the following priority
      actions be included in strategies to reduce the global impact of snake
      envenoming: (a) collection of accurate global snakebite incidence, mortality and
      morbidity data to underpin advocacy efforts and help design public health
      campaigns; (b) promotion of (i) public education prevention campaigns; (ii)
      transport systems to improve access to hospitals and (iii) establishment of
      regional antivenom-efficacy testing facilities to ensure antivenoms'
      effectiveness and safety;

PMID- 27886136
TI  - Interactions between the Multicolored Asian Lady Beetle Harmonia axyridis and the
      Parasitoid Dinocampus coccinellae.
AB  - Harmonia axyridis (Pallas) has been introduced either intentionally or
      accidentally in different areas outside its native range, where it is often
      regarded as invasive. Dinocampus coccinellae (Schrank) has been recorded to
      parasitize H. axyridis in the field, both in the native and introduced areas,
      Italy included. The percent of parasitism found in our field investigation was
      low (four percent). The effect of exposure time of H. axyridis to D. coccinellae
      and the impact of parasitization on host longevity, oviposition capacity and egg
      fertility were evaluated in the laboratory. The acceptance and suitability of H.
      axyridis as host for D. coccinellae were then studied, in comparison with the
      native coccinellid Adalia bipunctata (L.), which shares the same ecological
      niche. The effects of parasitization on female longevity and reproduction
      capacity in the exotic vs. the indigenous lady beetle were also investigated. The
      overall results showed that D. coccinellae negatively affected the fitness of H.
      axyridis, more than that of A. bipunctata. The parasitoid may thus play a
      marginal role in controlling the populations of the Asian lady beetle, without
      representing a threat to A. bipunctata.

PMID- 27886137
TI  - Ecosystem Services Insights into Water Resources Management in China: A Case of
      Xi'an City.
AB  - Global climate and environmental changes are endangering global water resources;
      and several approaches have been tested to manage and reduce the pressure on
      these decreasing resources. This study uses the case study of Xi'an City in China
      to test reasonable and effective methods to address water resource shortages. The
      study generated a framework combining ecosystem services and water resource
      management. Seven ecosystem indicators were classified as supply services,
      regulating services, or cultural services. Index values for each indicator were
      calculated, and based on questionnaire results, each index's weight was
      calculated. Using the Likert method, we calculated ecosystem service supplies in
      every region of the city. We found that the ecosystem's service capability is
      closely related to water resources, providing a method for managing water
      resources. Using Xi'an City as an example, we apply the ecosystem services
      concept to water resources management, providing a method for decision makers.

PMID- 27886139
TI  - Research on the Relationship between Reaction Ability and Mental State for Online
      Assessment of Driving Fatigue.
AB  - Background: Driving fatigue affects the reaction ability of a driver. The aim of
      this research is to analyze the relationship between driving fatigue,
      physiological signals and driver's reaction time. Methods: Twenty subjects were
      tested during driving. Data pertaining to reaction time and physiological signals
      including electroencephalograph (EEG) were collected from twenty simulation
      experiments. Grey correlation analysis was used to select the input variable of
      the classification model. A support vector machine was used to divide the mental
      state into three levels. The penalty factor for the model was optimized using a
      genetic algorithm. Results: The results show that alpha/beta has the greatest
      correlation to reaction time. The classification results show an accuracy of 86%,
      a sensitivity of 87.5% and a specificity of 85.53%. The average increase of
      reaction time is 16.72% from alert state to fatigued state. Females have a faster
      decrease in reaction ability than males as driving fatigue accumulates. Elderly
      drivers have longer reaction times than the young. Conclusions: A grey
      correlation analysis can be used to improve the classification accuracy of the
      support vector machine (SVM) model. This paper provides basic research that
      online detection of fatigue can be performed using only a simple device, which is
      more comfortable for users.

PMID- 27886138
TI  - Time Trend in Psychotropic Medication Use in Spain: A Nationwide Population-Based
      Study.
AB  - Background: We performed an epidemiologic study to analyze nationwide time trends
      in adult psychotropic drug use over a period from 2006 to 2012, and to identify
      those factors associated with the likelihood of consumption of these drugs during
      the study period; Methods: Cross-sectional study on psychotropic medication in
      the Spanish adult population. We used secondary individualized data drawn from
      the 2006 and 2012 Spanish National Health Surveys (SNHS). The dependent variable
      was the use of psychotropic drugs in the previous two weeks. Independent
      variables included socio-demographic characteristics, comorbidity, lifestyles and
      healthcare resource utilization. Using logistic multivariate regression models,
      we analyzed the temporal evolution of psychotropic medication consumption between
      2006 and 2012 in both sexes; Results: The prevalence of psychotropic drug use was
      significantly greater in women (18.14% vs. 8.08% in 2012 (p < 0.05). In Spanish
      women, the variables associated with a greater probability of psychotropic use
      were, age, unemployment (adjusted odds ratio (AOR), 1.60; 95% CI, 1.24-2.07),
      negative perception of health or taking non-psychotropic drugs. Among men,
      psychotropic use is associated with presence of chronic disease, negative
      perception of health (AOR, 3.27; 95% CI, 2.62-4.07 in 2012) or inactive status;
      Conclusions: Between 2006 and 2012, the probability of having taken psychotropic
      drugs increased by 16% among women. Unemployed women aged >=45 years with a
      negative perception of their health constitute a clear risk profile in terms of
      psychotropic drug use. Inactive men who have a negative perception of their
      health are the group most likely to consume psychotropic drugs.

PMID- 27886140
TI  - English Stop-Smoking Services: One-Year Outcomes.
AB  - The UK is a global leader in stop-smoking support-providing free behavioral
      support and cessation medication via stop smoking services (SSS) without charge
      to smokers. This study aimed to explore the client and service characteristics
      associated with abstinence 52 weeks after quitting. A prospective cohort study of
      3057 SSS clients in nine different areas of England who began their quit attempt
      between March 2012 and March 2013 was conducted. Important determinants of long
      term quitting were assessed through quit rates and multivariable logistic
      regression. Our results showed that the overall weighted carbon monoxide
      validated quit rate for clients at 52 weeks was 7.7% (95% confidence interval
      (CI) 6.6-9.0). The clients of advisors, whose main role was providing stop
      smoking support, were more likely to quit long-term than advisors who had a
      generalist role in pharmacies or general practices (odds ratio (OR) 2.3 (95% CI
      1.2-4.6)). Clients were more likely to achieve abstinence through group support
      than one-to-one support (OR 3.4 (95% CI 1.7-6.7)). Overall, one in thirteen
      people who set a quit date with the National Health Service (NHS) Stop-Smoking
      Service maintain abstinence for a year. Improving abstinence is likely to require
      a greater emphasis on providing specialist smoking cessation support. Results
      from this study suggest that over 18,000 premature deaths were prevented through
      longer-term smoking cessation achieved by smokers who accessed SSS in England
      from March 2012 to April 2013, but outcomes varied by client characteristic and
      the type of support provided.

PMID- 27886141
TI  - Comprehensive Transcriptome Analysis Provides Evidence of Local Thermal
      Adaptation in Three Loaches (Genus: Misgurnus).
AB  - The geographic distribution of three Misgurnus species, M. anguillicaudatus, M.
      bipartitus, and M. mohoity, displays a specific pattern in China, coincident with
      temperature zones. In this study, we sequenced the transcriptomes of these three
      species and used the sequences to investigate the lineage-specific adaptations
      within the genus Misgurnus. In total, 51 orphan genes (19 in M. anguillicaudatus,
      18 in M. bipartitus, and 14 in M. mohoity) that may contribute to the species
      specific adaptations were identified. An analysis of 1392 one-to-one orthologous
      genes revealed significantly higher ratios of nonsynonymous-to-synonymous
      substitutions in the M. mohoity lineage than in M. anguillicaudatus. The genes
      displaying signatures of positive selection and rapid evolution in Misgurnus were
      involved in four function categories, (1) energy metabolism; (2) signal
      transduction; (3) membrane; and (4) cell proliferation or apoptosis, implying
      that these candidate genes play critical roles in the thermal adaptation of the
      fish to their living environments. We also detected more than five positively
      selected sites in cldn15lb and isca1, which function as important factors in
      paracellular Na+ transport and Fe/S cluster assembly, respectively. Overall, our
      study provides valuable insights into the adaptive evolution of loaches from
      different temperature zones in China and is a foundation for future studies to
      clarify the genetic basis of temperature adaptation in fishes.

PMID- 27886142
TI  - Gender Differences in the Application of Spanish Criteria for Initiation of
      Enzyme Replacement Therapy for Fabry Disease in the Fabry Outcome Survey.
AB  - Both male/female patients with Fabry disease (FD) may receive enzyme replacement
      therapy (ERT). Previously published analyses of the Fabry Outcome Survey (FOS;
      Shire-sponsored) database suggested gender differences in timing of ERT
      initiation. We assessed alignment of criteria for ERT initiation in the Spanish
      adult population included in FOS with recommendations of a Spanish national
      consensus. This retrospective analysis examined baseline clinical data of 88
      adults (49 females) enrolled in the FOS database up to August 2014. Thirty-five
      (39.8%) patients were not receiving ERT: five (12.8%) males and 30 (61.2%)
      females. Baseline disease severity on the FOS-derived Mainz Severity Score Index
      was lower in untreated males (median (interquartile range), 0.0 (0.0-1.0)) than
      treated males (TM; 15.0 (7.5-26.5)), and was similar in untreated and treated
      females. The percentage of untreated females with at least one criterion for
      treatment initiation was 76.7% versus 100.0% of treated females (p = 0.0340) and
      97.1% (p = 0.0210) of TM. In discordance with Spanish consensus recommendations,
      a substantial number of females with evidence of FD who might benefit from ERT
      have not yet initiated treatment. These results suggest unequal gender
      perceptions with respect to ERT initiation in Spain.

PMID- 27886143
TI  - Neonatal Diesel Exhaust Particulate Exposure Does Not Predispose Mice to Adult
      Cardiac Hypertrophy or Heart Failure.
AB  - Background: We have previously reported that in utero and early life exposure to
      diesel exhaust particulates predisposes mice to adult heart failure, and that in
      utero exposure alone is sufficient to confer this predisposition. This follow up
      study addresses whether neonatal exposure alone can also confer this
      predisposition. Methods: Newborn male C57BL/6 mice were exposed to diesel exhaust
      (DE) particulates immediately after birth until weaning at 21 days of age,
      whereupon they were transferred to filtered air (FA) conditions. At the age of 12
      weeks, transverse aortic constriction (TAC) was performed followed by weekly
      echocardiography for three weeks. After the last echocardiogram, mice were
      euthanized for organ harvest, gravimetry and histology. Results: Neonatal
      exposure to DE particulates did not increase susceptibility to cardiac
      hypertrophy or heart failure after TAC when compared to FA exposed controls
      (ventricular weight/body weight ratio 7.505 vs. 7.517 mg/g, p = Not Significant
      (NS)). The left ventricular ejection fraction after TAC was similar between
      groups at one week, two weeks, and three weeks after procedure. Histological
      analysis showed no difference in the degree of cardiac hypertrophy or fibrosis.
      Conclusions: Neonatal exposure to DE particulates does not predispose mice to TAC
      induced cardiac hypertrophy and heart failure in adulthood, in contrast to
      previously published results showing susceptibility due to in utero exposure.

PMID- 27886144
TI  - Cuticular Lipids as a Cross-Talk among Ants, Plants and Butterflies.
AB  - Even though insects and plants are distantly related organisms, they developed an
      integument which is functionally and structurally similar. Besides functioning as
      a physical barrier to cope with abiotic and biotic stress, this interface, called
      cuticle, is also a source of chemical signaling. Crucial compounds with this
      respect are surface lipids and especially cuticular hydrocarbons (CHCs). This
      review is focused on the role of CHCs in fostering multilevel relationships among
      ants, plants and Lepidoptera (primarily butterflies). Indeed, particular traits
      of ants as eusocial organisms allowed the evolution and the maintenance of a
      variety of associations with both plants and animals. Basic concepts of
      myrmecophilous interactions and chemical deception strategies together with
      chemical composition, biosynthetic pathways and functions of CHCs as molecular
      cues of multitrophic systems are provided. Finally, the need to adopt a
      multidisciplinary and comprehensive approach in the survey of complex models is
      discussed.

PMID- 27886135
TI  - Soy and Health Update: Evaluation of the Clinical and Epidemiologic Literature.
AB  - Soyfoods have long been recognized as sources of high-quality protein and
      healthful fat, but over the past 25 years these foods have been rigorously
      investigated for their role in chronic disease prevention and treatment. There is
      evidence, for example, that they reduce risk of coronary heart disease and breast
      and prostate cancer. In addition, soy alleviates hot flashes and may favorably
      affect renal function, alleviate depressive symptoms and improve skin health.
      Much of the focus on soyfoods is because they are uniquely-rich sources of
      isoflavones. Isoflavones are classified as both phytoestrogens and selective
      estrogen receptor modulators. Despite the many proposed benefits, the presence of
      isoflavones has led to concerns that soy may exert untoward effects in some
      individuals. However, these concerns are based primarily on animal studies,
      whereas the human research supports the safety and benefits of soyfoods. In
      support of safety is the recent conclusion of the European Food Safety Authority
      that isoflavones do not adversely affect the breast, thyroid or uterus of
      postmenopausal women. This review covers each of the major research areas
      involving soy focusing primarily on the clinical and epidemiologic research.
      Background information on Asian soy intake, isoflavones, and nutrient content is
      also provided.

PMID- 27886146
TI  - A Robot-Based Tool for Physical and Cognitive Rehabilitation of Elderly People
      Using Biofeedback.
AB  - This publication presents a complete description of a technological solution
      system for the physical and cognitive rehabilitation of elderly people through a
      biofeedback system, which is combined with a Lego robot. The technology used was
      the iOS's (iPhone Operating System) Objective-C programming language and its
      XCode programming environment; and SQLite in order to create the database. The
      biofeedback system is implemented by the use of two biosensors which are, in
      fact, a Microsoft band 2 in order to register the user's heart rate and a MYO
      sensor to detect the user's arm movement. Finally, the system was tested with
      seven elderly people from La Santa y Real Casa de la Misericordia nursing home in
      Bilbao. The statistical assessment has shown that the users are satisfied with
      the usability of the system, with a mean score of 79.29 on the System Usability
      Scale (SUS) questionnaire.

PMID- 27886145
TI  - Role of Endogenous and Exogenous Tocopherols in the Lipid Stability of Marine Oil
      Systems: A Review.
AB  - In marine organisms primarily intended for human consumption, the quality of the
      muscle and the extracted oils may be affected by lipid oxidation during storage,
      even at low temperatures. This has led to a search for alternatives to maintain
      quality. In this sense, antioxidant compounds have been used to prevent such
      lipid deterioration. Among the most used compounds are tocopherols, which, due to
      their natural origin, have become an excellent alternative to prevent or retard
      lipid oxidation and maintain the quality of marine products. Tocopherols as
      antioxidants have been studied both exogenously and endogenously. Exogenous
      tocopherols are often used by incorporating them into plastic packaging films or
      adding them directly to fish oil. It has been observed that exogenous tocopherols
      incorporated in low concentrations maintain the quality of both muscle and the
      extracted oils during food storage. However, it has been reported that
      tocopherols applied at higher concentrations act as a prooxidant molecule,
      probably because their reactions with singlet oxygen may generate free radicals
      and cause the oxidation of polyunsaturated fatty acids in fish oils. However,
      when tocopherols are included in a fish diet (endogenous tocopherols), the
      antioxidant effect on the muscle lipids is more effective due to their
      incorporation into the membrane lipids, which can help extend the shelf life of
      seafood by reducing the lipid deterioration that occurs due to antioxidant
      synergy with other phenolic compounds used supplements in fish muscle. This
      review focuses on the most important studies in this field and highlights the
      potential of using tocopherols as antioxidants in marine oils.

PMID- 27886147
TI  - Emerging Phytochemicals for the Prevention and Treatment of Head and Neck Cancer.
AB  - Despite the development of more advanced medical therapies, cancer management
      remains a problem. Head and neck squamous cell carcinoma (HNSCC) is a
      particularly challenging malignancy and requires more effective treatment
      strategies and a reduction in the debilitating morbidities associated with the
      therapies. Phytochemicals have long been used in ancient systems of medicine, and
      non-toxic phytochemicals are being considered as new options for the effective
      management of cancer. Here, we discuss the growth inhibitory and anti-cell
      migratory actions of proanthocyanidins from grape seeds (GSPs), polyphenols in
      green tea and honokiol, derived from the Magnolia species. Studies of these
      phytochemicals using human HNSCC cell lines from different sub-sites have
      demonstrated significant protective effects against HNSCC in both in vitro and in
      vivo models. Treatment of human HNSCC cell lines with GSPs, (-)-epigallocatechin
      3-gallate (EGCG), a polyphenolic component of green tea or honokiol reduced cell
      viability and induced apoptosis. These effects have been associated with
      inhibitory effects of the phytochemicals on the epidermal growth factor receptor
      (EGFR), and cell cycle regulatory proteins, as well as other major tumor
      associated pathways. Similarly, the cell migration capacity of HNSCC cell lines
      was inhibited. Thus, GSPs, honokiol and EGCG appear to be promising bioactive
      phytochemicals for the management of head and neck cancer.

PMID- 27886148
TI  - Extraction of Opuntia dillenii Haw. Polysaccharides and Their Antioxidant
      Activities.
AB  - Use of natural polysaccharides in medicine and food has wide interest in
      research. In this study, we extracted and purified some polysaccharides from
      cactus Opuntia dillenii Haw. (ODP). Some preliminary functions of these products
      were characterized. Under the optimal purification conditions, the yield of ODP
      extracted from the 2-4 month-old Opuntia dillenii Haw. (T-ODP) was 30.60% +/-
      0.40%, higher than that of ODP from the 5-10 month-old materials (O-ODP) (18.97%
      +/- 0.58%). The extracted ODP was purified by DEAE sepharose fast flow anion
      exchange and Sephacryl S-400 chromatography with four fractions obtained (ODP-Ia,
      ODP-Ib, ODP-IIa and ODP-IIb). Analysis with UV-vis chromatography indicated that
      ODP-Ia and ODP-IIa were relatively homogeneous molecules with a molecular weight
      of 339 kD and 943 kD, respectively. Results of infrared spectroscopy indicated
      that ODP, ODP-Ia, and ODP-IIa were acidic polysaccharides. Further, the
      antioxidant activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radical,
      hydroxyl radicals, and superoxide radical in vitro demonstrated that the T-ODP
      exhibited higher antioxidant activity than the O-ODP, and the purified fraction
      (ODP-Ia) was superior to the ODP. These results will offer a theoretical basis
      for further research on the structure-function relationship of ODP and the
      rational utilization of Opuntia dillenii Haw.

PMID- 27886149
TI  - Toward Optimal Computation of Ultrasound Image Reconstruction Using CPU and GPU.
AB  - An ultrasound image is reconstructed from echo signals received by array elements
      of a transducer. The time of flight of the echo depends on the distance between
      the focus to the array elements. The received echo signals have to be delayed to
      make their wave fronts and phase coherent before summing the signals. In digital
      beamforming, the delays are not always located at the sampled points. Generally,
      the values of the delayed signals are estimated by the values of the nearest
      samples. This method is fast and easy, however inaccurate. There are other
      methods available for increasing the accuracy of the delayed signals and,
      consequently, the quality of the beamformed signals; for example, the in-phase
      (I)/quadrature (Q) interpolation, which is more time consuming but provides more
      accurate values than the nearest samples. This paper compares the signals after
      dynamic receive beamforming, in which the echo signals are delayed using two
      methods, the nearest sample method and the I/Q interpolation method. The
      comparisons of the visual qualities of the reconstructed images and the qualities
      of the beamformed signals are reported. Moreover, the computational speeds of
      these methods are also optimized by reorganizing the data processing flow and by
      applying the graphics processing unit (GPU). The use of single and double
      precision floating-point formats of the intermediate data is also considered. The
      speeds with and without these optimizations are also compared.

PMID- 27886151
TI  - Micro-Doppler Based Classification of Human Aquatic Activities via Transfer
      Learning of Convolutional Neural Networks.
AB  - Accurate classification of human aquatic activities using radar has a variety of
      potential applications such as rescue operations and border patrols.
      Nevertheless, the classification of activities on water using radar has not been
      extensively studied, unlike the case on dry ground, due to its unique challenge.
      Namely, not only is the radar cross section of a human on water small, but the
      micro-Doppler signatures are much noisier due to water drops and waves. In this
      paper, we first investigate whether discriminative signatures could be obtained
      for activities on water through a simulation study. Then, we show how we can
      effectively achieve high classification accuracy by applying deep convolutional
      neural networks (DCNN) directly to the spectrogram of real measurement data. From
      the five-fold cross-validation on our dataset, which consists of five aquatic
      activities, we report that the conventional feature-based scheme only achieves an
      accuracy of 45.1%. In contrast, the DCNN trained using only the collected data
      attains 66.7%, and the transfer learned DCNN, which takes a DCNN pre-trained on a
      RGB image dataset and fine-tunes the parameters using the collected data,
      achieves a much higher 80.3%, which is a significant performance boost.

PMID- 27886150
TI  - Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P
      Glycoprotein-Mediated Drug Transport.
AB  - P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and
      vincristine. Our previous study demonstrated that imperatorin increased the
      intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated
      drug efflux. However; the underlying mechanism was not known. The present study
      investigated the mechanism by which imperatorin promotes P-gp-mediated drug
      transport. We used molecular docking to predict the binding force between
      imperatorin and P-gp and the effect of imperatorin on P-gp activity. P-gp efflux
      activity and P-gp ATPase activity were measured using a rhodamine 123 (Rh-123)
      accumulation assay and a Pgp-GloTM assay; respectively. The fluorescent probe 1,6
      diphenyl-1,3,5-hexatriene (DPH) was used to assess cellular membrane fluidity in
      MDCK-MDR1 cells. Western blotting was used to analyze the effect of imperatorin
      on P-gp expression; and P-gp mRNA levels were assessed by qRT-PCR. Molecular
      docking results demonstrated that the binding force between imperatorin and P-gp
      was much weaker than the force between P-gp and verapamil (a P-gp substrate).
      Imperatorin activated P-gp ATPase activity; which had a role in the inhibition of
      P-gp activity. Imperatorin promoted Rh-123 accumulation in MDCK-MDR1 cells and
      decreased cellular membrane fluidity. Western blotting demonstrated that
      imperatorin inhibited P-gp expression; and qRT-PCR revealed that imperatorin down
      regulated P-gp (MDR1) gene expression. Imperatorin decreased P-gp-mediated drug
      efflux by inhibiting P-gp activity and the expression of P-gp mRNA and protein.
      Our results suggest that imperatorin could down-regulate P-gp expression to
      overcome multidrug resistance in tumors.

PMID- 27886152
TI  - Screening for Triterpenoid Saponins in Plants Using Hyphenated Analytical
      Platforms.
AB  - Recently the number of studies investigating triterpenoid saponins has
      drastically increased due to their diverse and potentially attractive biological
      activities. Currently the literature contains chemical structures of few hundreds
      of triterpenoid saponins of plant and animal origin. Triterpenoid saponins
      consist of a triterpene aglycone with one or more sugar moieties attached to it.
      However, due to similar physico-chemical properties, isolation and identification
      of a large diversity of triterpenoid saponins remain challenging. This study
      demonstrates a methodology to screen saponins using hyphenated analytical
      platforms, GC-MS, LC-MS/MS, and LC-SPE-NMR/MS, in the example of two different
      phenotypes of the model plant Barbarea vulgaris (winter cress), glabrous (G) and
      pubescent (P) type that are known to differ by their insect resistance. The
      proposed methodology allows for detailed comparison of saponin profiles from
      intact plant extracts as well as saponin aglycone profiles from hydrolysed
      samples. Continuously measured 1D proton NMR data during LC separation along with
      mass spectrometry data revealed significant differences, including contents of
      saponins, types of aglycones and numbers of sugar moieties attached to the
      aglycone. A total of 49 peaks were tentatively identified as saponins from both
      plants; they are derived from eight types of aglycones and with 2-5 sugar
      moieties. Identification of two previously known insect-deterrent saponins,
      hederagenin cellobioside and oleanolic acid cellobioside, demonstrated the
      applicability of the methodology for relatively rapid screening of bioactive
      compounds.

PMID- 27886153
TI  - A Dual Frequency Carrier Phase Error Difference Checking Algorithm for the GNSS
      Compass.
AB  - The performance of the Global Navigation Satellite System (GNSS) compass is
      related to the quality of carrier phase measurement. How to process the carrier
      phase error properly is important to improve the GNSS compass accuracy. In this
      work, we propose a dual frequency carrier phase error difference checking
      algorithm for the GNSS compass. The algorithm aims at eliminating large carrier
      phase error in dual frequency double differenced carrier phase measurement
      according to the error difference between two frequencies. The advantage of the
      proposed algorithm is that it does not need additional environment information
      and has a good performance on multiple large errors compared with previous
      research. The core of the proposed algorithm is removing the geographical
      distance from the dual frequency carrier phase measurement, then the carrier
      phase error is separated and detectable. We generate the Double Differenced
      Geometry-Free (DDGF) measurement according to the characteristic that the
      different frequency carrier phase measurements contain the same geometrical
      distance. Then, we propose the DDGF detection to detect the large carrier phase
      error difference between two frequencies. The theoretical performance of the
      proposed DDGF detection is analyzed. An open sky test, a manmade multipath test
      and an urban vehicle test were carried out to evaluate the performance of the
      proposed algorithm. The result shows that the proposed DDGF detection is able to
      detect large error in dual frequency carrier phase measurement by checking the
      error difference between two frequencies. After the DDGF detection, the accuracy
      of the baseline vector is improved in the GNSS compass.

PMID- 27886154
TI  - On Performance Analysis of Protective Jamming Schemes in Wireless Sensor
      Networks.
AB  - Wireless sensor networks (WSNs) play an important role in Cyber Physical Social
      Sensing (CPSS) systems. An eavesdropping attack is one of the most serious
      threats to WSNs since it is a prerequisite for other malicious attacks. In this
      paper, we propose a novel anti-eavesdropping mechanism by introducing friendly
      jammers to wireless sensor networks (WSNs). In particular, we establish a
      theoretical framework to evaluate the eavesdropping risk of WSNs with friendly
      jammers and that of WSNs without jammers. Our theoretical model takes into
      account various channel conditions such as the path loss and Rayleigh fading, the
      placement schemes of jammers and the power controlling schemes of jammers.
      Extensive results show that using jammers in WSNs can effectively reduce the
      eavesdropping risk. Besides, our results also show that the appropriate placement
      of jammers and the proper assignment of emitting power of jammers can not only
      mitigate the eavesdropping risk but also may have no significant impairment to
      the legitimate communications.

PMID- 27886155
TI  - Utilizing a Wristband Sensor to Measure the Stress Level for People with
      Dementia.
AB  - Stress is a common problem that affects most people with dementia and their
      caregivers. Stress symptoms for people with dementia are often measured by
      answering a checklist of questions by the clinical staff who work closely with
      the person with the dementia. This process requires a lot of effort with
      continuous observation of the person with dementia over the long term. This
      article investigates the effectiveness of using a straightforward method, based
      on a single wristband sensor to classify events of "Stressed" and "Not stressed"
      for people with dementia. The presented system calculates the stress level as an
      integer value from zero to five, providing clinical information of behavioral
      patterns to the clinical staff. Thirty staff members participated in this
      experiment, together with six residents suffering from dementia, from two nursing
      homes. The residents were equipped with the wristband sensor during the day, and
      the staff were writing observation notes during the experiment to serve as ground
      truth. Experimental evaluation showed relationships between staff observations
      and sensor analysis, while stress level thresholds adjusted to each individual
      can serve different scenarios.

PMID- 27886157
TI  - Intraoperative seizures and seizures outcome in patients underwent awake
      craniotomy.
AB  - BACKGROUND: Awake craniotomies (AC) could reduce neurological deficits compared
      with patients under general anesthesia, however, intraoperative seizure is a
      major reason causing awake surgery failure. The purpose of the study was to give
      a comprehensive overview the published articles focused on seizure incidence in
      awake craniotomy. METHODS: Bibliographic searches of the EMBASE, MEDLINE,were
      performed to identify articles and conference abstracts that investigated the
      intraoperative seizure frequency of patients underwent AC. RESULTS: Twenty-five
      studies were included in this meta-analysis. Among the 25 included studies, one
      was randomized controlled trials and 5 of them were comparable studies. The
      pooled data suggested the general intraoperative seizure(IOS) rate for patients
      with AC was 8%(fixed effect model), sub-group analysis identified IOS rate for
      glioma patients was 8% and low grade patients was 10%. The pooled data showed
      early seizure rates of AC patients was 11% and late seizure rates was 35%.
      CONCLUSION: This systematic review and meta-analysis shows that awake craniotomy
      is a safe technique with relatively low intraoperative seizure occurrence.
      However, few RCTs were available, and the acquisition of further evidence through
      high-quality RCTs is highly recommended.

PMID- 27886156
TI  - Conformity Scores Differentiate Older Hemodialyzed Patients and Patients with
      Continuous Peritoneal Dialysis.
AB  - BACKGROUND Conformity is a psychological variable related to the propensity of an
      individual to match his or her behavior and opinion to the perceived social and
      cultural norm, even if these do not represent the true beliefs of the person. The
      aim of the present study was to investigate whether the psychological variable of
      conformity is different in two distinct modes of renal replacement therapy (RRT)
      in end-stage renal disease (ESRD). MATERIAL AND METHODS A total of 56
      hemodialyzed patients (HD group), 45 continuous ambulatory peritoneal dialysis
      patients (CAPD group) and 62 healthy volunteers (CONTR group) were enrolled in
      the study. The Social Appraisal Questionnaire (SAQ) was employed, and chart
      review was performed to collect clinical data. RESULTS When age was not a factor,
      the conformity measure was significantly higher in the HD group compared with the
      CAPD and CONTR groups. The lowest conformity was found in healthy participants
      who were asked to imagine an acute medical problem. The highest conformity was
      found in older HD and CAPD patients. CONCLUSIONS Being chronically ill and having
      adaptable views may be more favorable traits for coping with ESRD in dialyzed
      patients, especially in elderly HD patients. On the other hand, conformity can be
      deleterious if CAPD patients decide to overlook certain facts or not confront the
      medical aspects of their condition.

PMID- 27886158
TI  - Recanalization and rupture after intracranial aneurysm treatment.
AB  - BACKGROUND: Treatment of intra cranial aneurysm (ICA) can sometimes required
      several procedures. The aim of this study is to analyze the risk of
      recanalization and rupture recurrence after ICA treatment by endovascular coiling
      (EVC) or surgical clipping (SC) on a very long follow-up. METHODS: Clinical data
      of 373 consecutive patients treated in our group between January 1996 and
      December 2006 as well by EVC as by SC for ruptured (RIA) or unruptured
      intracranial aneurysm (UIA), were reviewed. Patients were followed up at least to
      August 2009. First radiologic follow-up done six months after EVC and between
      three and five years after SC (median time: 5 years)). All patients underwent a
      clinical follow-up after treatment, at least by telephonic communication (median
      time: 6 years). RESULTS: Out of 197 patients with 198 RIAs, 82 (42 %) patients
      underwent an endovascular treatment and 115 (58%) were allocated to surgical
      treatment. From a total of 176 patients with 229 UIAs, 66 (37.5%) patients were
      treated by 74 EVC; and 110 (62.5%) patients were treated with 124 surgical
      procedures. Fifteen recanalizations of coiled RIAs were detected and only one in
      the surgical group (27% vs. 2%; p= 0.0008). Of the 15 recanalizations in the EVC
      group, 6 (40%) were initially completely occluded. We observed two rebleedings,
      one in each group (1.4% for EVC; 1% for SC; p=0.8). CONCLUSIONS: Our findings
      during the longest reported follow-up confirm a greater risk of recanalization
      for RIA treated by EVC without so far a significant difference in the rerupture
      risk.

PMID- 27886159
TI  - Cardiac monitoring in patients on trastuzumab: correlation of ultrasound and
      radionuclide ventriculography.
AB  - BACKGROUND: Guidance on cardiac surveillance during adjuvant trastuzumab therapy
      remains elusive. The recommended methods are two-dimensional echocardiography (2D
      ECHO) and electrocardiography gated equilibrium radionuclide ventriculography
      (RNV). We assessed the correlation and possible specific merits of these two
      methods. METHODS: In a prospective cohort study in patients undergoing post
      anthracycline adjuvant trastuzumab therapy, clinical assessment, 2D-ECHO and RNV
      were performed at baseline, 4, 8 and 12 months. The correlation between used
      methods was estimated with Pearson's correlation coefficient and Bland-Altman
      analysis. RESULTS: Ninety-two patients (mean age 53.6+/-9.0 years) were included.
      The correlation of LVEF measured by ECHO and RNV at each time point was
      statistically insignificant. Values obtained by ECHO were on average higher (3.7%
      to 4.5%). A decline in LVEF of >=10% from baseline was noticed in 19 (24.4%) and
      13 (14.9%) patients with ECHO and RNV, respectively, however in only one patient
      by both methods simultaneously. A decline in LVEF of >=10% to below 50% was found
      in three and none patients according to RNV and ECHO measurements, respectively.
      CONCLUSIONS: There is a weak correlation of ECHO and RNV measurements in
      individual patient, the results obtained by the methods are not interchangeable.
      LVEF values determined by 2D-ECHO were on average higher compared to RNV
      determined ones. When in an asymptomatic patient a decline in LVEF requiring
      treatment interruption is detected by RNV ECHO re-evaluation and referral to a
      cardiologist is advised.

PMID- 27886160
TI  - Left ventricular end-diastolic volume as early indicator of trastuzumab-related
      cardiotoxicity in HER2+ breast cancer patients: results from a single-center
      retrospective study.
AB  - BACKGROUND: Adjuvant trastuzumab therapy increases survival rates in patients
      with early HER2-positive breast cancer, although it can be potentially
      cardiotoxic. The aim of this study was to evaluate the prevalence of left
      ventricular (LV) systolic dysfunction; and the relationship between the presence
      of cardiovascular risk factors, cardiac therapy and/or echocardiographic
      parameters of systolic function at baseline and the development of cardiotoxicity
      in such patients. METHODS: A total of 227 patients were retrospectively reviewed.
      Cardiotoxicity was defined as a decrease in LV ejection fraction (EF) below 50%
      or an absolute decrease of >10 points below the baseline value or any indication
      of heart failure. Each patient underwent echocardiography at baseline and at
      follow-up every three months. RESULTS: The prevalence of cardiotoxicity was 17.6%
      (15.4% asymptomatic, 2.2% symptomatic). Patients developing LV dysfunction
      presented hypertension (P=0.041) and diabetes (P=0.01) and used cardiac therapy
      at baseline more frequently. Smoke habit, age >50 and use of angiotensin
      converting enzyme (ACE)-inhibitors, were independent predictors of cardiac
      damage. Furthermore, patients with LV dysfunction showed baseline LV end
      diastolic volume (EDV) higher than those who did not and baseline EDV (OR=1.02;
      95% CI: 1.00-1.04; P=0.027) independently predicted cardiotoxicity with 58 mL/m2
      as best cut-off point (AUC=0.65, 95% CI: 0.55-0.75]). CONCLUSIONS: The prevalence
      of trastuzumab-related cardiotoxicity in patients with HER2-positive early breast
      cancer is relatively frequent, although asymptomatic in most cases. Baseline EDV
      resulted as independent predictor of cardiotoxicity suggesting that EDV may be
      more reliable than LVEF to identify patients at higher risk of developing cardiac
      damage.

PMID- 27886161
TI  - Is there still a role for cardiac CT in the emergency department in the era of
      highly-sensitive troponins?
AB  - Physicians practicing cardiovascular medicine are every day confronted with
      patients presenting with symptoms suggestive of an acute coronary syndrome (ACS).
      Over the years, there have been substantial technical advances, such as the
      introduction of new non-invasive imaging techniques and the introduction of new
      highly sensitive cardiac biomarkers. Physicians have adopted these new assets and
      have become more experienced with them thus improving medical care. Nevertheless,
      the search for an efficient, yet safe diagnostic work-up for patients presenting
      with symptoms suggestive of ACS is ongoing. A large proportion of patients will
      require some form of non-invasive testing and the choice for the diagnostic
      modality as well as its timing are important steps in this process. Cardiac
      computed tomography (CT), a non-invasive imaging technique that rapidly provides
      visualization of the coronary artery tree, is an attractive option, with its
      unparalleled negative predictive value for obstructive coronary artery disease
      (CAD). With the introduction of highly-sensitive troponins (hsTn), the role of
      non-invasive testing, including cardiac CT, has changed. This review will provide
      an oversight on what is known about cardiac CT in acute chest presentations.
      Furthermore, we will discuss the changing role of cardiac CT in the era of hsTn
      and the possibility of their combined use in the work-up of suspected ACS
      patients. hsTn is currently an established tool for the diagnosis and triage of
      patients with suspected ACS. The role of cardiac CT has shifted now to a
      secondary, comprehensive rule-out test in patients with inconclusive biomarker
      status, providing information on stenosis severity, plaque burden, high-risk
      features and the presence of other serious conditions that can also give rise to
      hsTn.

PMID- 27886162
TI  - miR-146a rs2910164 and hepatocellular carcinoma: a meta-analysis.
AB  - INTRODUCTION: Single nucleotide polymorphism in miRNAs can alter its expression,
      thus can lead to the development of cancers. Many studies have explored the
      association between miR-146a rs2910164 (G>C) polymorphism and hepatocellular
      carcinoma (HCC) risk, but the results remains inconsistent. So, we performed this
      pooled analyses in order to get a precise result. EVIDENCE ACQUISITION: Odds
      ratios (OR) with 95% confidence intervals (CI), calculated by STATA software, was
      used to determine whether miR-146a rs2910164 polymorphism contributes to the risk
      of HCC. A comprehensive literature search was conducted on PubMed, Embase, Web of
      Science, and China National Knowledge Infrastructure up to May 30, 2016. EVIDENCE
      SYNTHESIS: A total of 14 studies including 5921 cases and 7005 controls were
      included in this meta-analysis. When all the eligible studies were pooled into
      this meta-analysis, the miR-146a rs2910164 was associated with a decreased risk
      of hepatocellular carcinoma (OR=0.90; 95% CI=0.82-0.98, P=0.01, allele model).
      CONCLUSIONS: Our meta-analysis supports that the miR-146a rs2910164 polymorphism
      contributes to the risk of HCC from currently available evidence.

PMID- 27886163
TI  - Alghedon Fentanyl Transdermal System.
AB  - The efficacy of transdermal fentanyl for cancer pain and chronic non-cancer pain
      (chronic lower back pain, rheumatoid arthritis, osteoarthritis, neuropathic pain)
      is well established. Several formulations of fentanyl transdermal systems have
      been developed to improve the drug delivery and prevent misuse of the active
      principle. The addition of a rate controlling membrane to the matrix system
      represented an important advance. The design and functional features of Alghedon
      patch are compared with other approved generic fentanyl transdermal systems,
      emphasizing the distinctiveness of Alghedon patch. Alghedon patch has no liquid
      component in the finished product, therefore no leakage of active ingredient from
      the system can occur. A rate-controlling membrane provides controlled release of
      the active substance from the matrix reservoir, ensuring that fentanyl delivery
      and entry into the microcirculation is not solely controlled by the skin's
      permeability to this active substance. Alghedon patch contains part of the drug
      (approximately 15%) in the skin-contact adhesive: this innovative solution allows
      to overcome a typical drawback of transdermal patches, i.e. the long lag-time
      before the drug appears in plasma after the first administration, and provides
      rapid analgesia during the first hours of administration. Alghedon Fentanyl
      Transdermal System employs materials commonly used in other transdermal
      applications and having established safety profiles. For each strength level, the
      fentanyl content - and, thus, the resulting residual fentanyl remaining in the
      patch after use - is at the lowest end of the range used in commercially
      available fentanyl patches, minimizing the potential for abuse and misuse.

PMID- 27886164
TI  - Fumarate drives EMT in renal cancer.

PMID- 27886165
TI  - Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity.
AB  - Circular RNAs are a class of non-coding RNAs that are receiving extensive
      attention. Despite reports showing circular RNAs acting as microRNA sponges, the
      biological functions of circular RNAs remain largely unknown. We show that in
      patient tumor samples and in a panel of cancer cells, circ-Foxo3 was minimally
      expressed. Interestingly, during cancer cell apoptosis, the expression of circ
      Foxo3 was found to be significantly increased. We found that silencing endogenous
      circ-Foxo3 enhanced cell viability, whereas ectopic expression of circ-Foxo3
      triggered stress-induced apoptosis and inhibited the growth of tumor xenografts.
      Also, expression of circ-Foxo3 increased Foxo3 protein levels but repressed p53
      levels. By binding to both, circ-Foxo3 promoted MDM2-induced p53 ubiquitination
      and subsequent degradation, resulting in an overall decrease of p53. With low
      binding affinity to Foxo3 protein, circ-Foxo3 prevented MDM2 from inducing Foxo3
      ubiquitination and degradation, resulting in increased levels of Foxo3 protein.
      As a result, cell apoptosis was induced by upregulation of the Foxo3 downstream
      target PUMA.

PMID- 27886166
TI  - Generation of single photons with highly tunable wave shape from a cold atomic
      ensemble.
AB  - The generation of ultra-narrowband, pure and storable single photons with widely
      tunable wave shape is an enabling step toward hybrid quantum networks requiring
      interconnection of remote disparate quantum systems. It allows interaction of
      quantum light with several material systems, including photonic quantum memories,
      single trapped ions and opto-mechanical systems. Previous approaches have offered
      a limited tuning range of the photon duration of at most one order of magnitude.
      Here we report on a heralded single photon source with controllable emission time
      based on a cold atomic ensemble, which can generate photons with temporal
      durations varying over three orders of magnitude up to 10 MUs without a
      significant change of the readout efficiency. We prove the nonclassicality of the
      emitted photons, show that they are emitted in a pure state, and demonstrate that
      ultra-long photons with nonstandard wave shape can be generated, which are
      ideally suited for several quantum information tasks.

PMID- 27886168
TI  - Hitting the right button: MAVS-mediated defense against HAV infection.
AB  - Studying the immune response against infection with hepatitis viruses is hampered
      by the lack of suitable preclinical model systems. A recent publication in
      Science identifies the cytosolic adapter molecule MAVS as being responsible for
      species restriction of infection with hepatitis A virus as well as linking
      cytosolic immune sensing in infected hepatocytes with innate effector functions
      and protective adaptive immunity.

PMID- 27886167
TI  - Mapping of long-range chromatin interactions by proximity ligation-assisted ChIP
      seq.

PMID- 27886169
TI  - The mitokine quest(ion).
AB  - Cells and organisms adapt to mitochondrial dysfunction by activating the
      mitochondrial unfolded protein response (UPR), which is regulated by
      mitochondrial-to-nuclear communication; and UPR activation can also be
      transmitted between different cell types suggesting a role in tissue
      coordination. Shao and colleagues now identify a neuronal circuit and a secreted
      neuropeptide required for cell non-autonomous UPR regulation.

PMID- 27886170
TI  - Tuning charge and correlation effects for a single molecule on a graphene device.
AB  - The ability to understand and control the electronic properties of individual
      molecules in a device environment is crucial for developing future technologies
      at the nanometre scale and below. Achieving this, however, requires the creation
      of three-terminal devices that allow single molecules to be both gated and imaged
      at the atomic scale. We have accomplished this by integrating a graphene field
      effect transistor with a scanning tunnelling microscope, thus allowing gate
      controlled charging and spectroscopic interrogation of individual tetrafluoro
      tetracyanoquinodimethane molecules. We observe a non-rigid shift in the
      molecule's lowest unoccupied molecular orbital energy (relative to the Dirac
      point) as a function of gate voltage due to graphene polarization effects. Our
      results show that electron-electron interactions play an important role in how
      molecular energy levels align to the graphene Dirac point, and may significantly
      influence charge transport through individual molecules incorporated in graphene
      based nanodevices.

PMID- 27886171
TI  - Transduction of group I mGluR-mediated synaptic plasticity by beta-arrestin2
      signalling.
AB  - Conventional signalling by the group I metabotropic glutamate receptors, mGluR1
      and mGluR5, occurs through G-protein coupling, but evidence suggests they might
      also utilize other, non-canonical effector pathways. Here we test whether group I
      mGluRs require beta-arrestin signalling during specific forms of plasticity at
      hippocampal excitatory synapses. We find that genetic ablation of beta-arrestin2,
      but not beta-arrestin1, results in deficits in plasticity mediated by mGlu1
      receptors in CA3 pyramidal neurons and by mGlu5 receptors in CA1 pyramidal
      neurons. Pharmacological studies additionally support roles for Src kinases and
      MAPK/ERK downstream of beta-arrestin2 in CA3 neurons. mGluR1 modulation of
      intrinsic conductances is otherwise preserved in beta-arrestin2-/- mice with the
      exception of a rebound depolarization, and non-mGluR-mediated long-term
      potentiation is unaltered. These results reveal a signalling pathway engaged by
      group I mGluRs to effect changes in synaptic and cell intrinsic physiology
      dependent upon beta-arrestin rather than G proteins. Pharmacological manipulation
      of mGluRs with effector-biased ligands could lead to novel therapies to treat
      neurological disease.

PMID- 27886172
TI  - Fundamental rate-loss trade-off for the quantum internet.
AB  - The quantum internet holds promise for achieving quantum communication-such as
      quantum teleportation and quantum key distribution (QKD)-freely between any
      clients all over the globe, as well as for the simulation of the evolution of
      quantum many-body systems. The most primitive function of the quantum internet is
      to provide quantum entanglement or a secret key to two points efficiently, by
      using intermediate nodes connected by optical channels with each other. Here we
      derive a fundamental rate-loss trade-off for a quantum internet protocol, by
      generalizing the Takeoka-Guha-Wilde bound to be applicable to any network
      topology. This trade-off has essentially no scaling gap with the quantum
      communication efficiencies of protocols known to be indispensable to long
      distance quantum communication, such as intercity QKD and quantum repeaters. Our
      result-putting a practical but general limitation on the quantum internet-enables
      us to grasp the potential of the future quantum internet.

PMID- 27886174
TI  - 5-Hydroxymethylcytosine localizes to enhancer elements and is associated with
      survival in glioblastoma patients.
AB  - Glioblastomas exhibit widespread molecular alterations including a highly
      distorted epigenome. Here, we resolve genome-wide 5-methylcytosine and 5
      hydroxymethylcytosine in glioblastoma through parallel processing of DNA with
      bisulfite and oxidative bisulfite treatments. We apply a statistical algorithm to
      estimate 5-methylcytosine, 5-hydroxymethylcytosine and unmethylated proportions
      from methylation array data. We show that 5-hydroxymethylcytosine is depleted in
      glioblastoma compared with prefrontal cortex tissue. In addition, the genomic
      localization of 5-hydroxymethylcytosine in glioblastoma is associated with
      features of dynamic cell-identity regulation such as tissue-specific
      transcription and super-enhancers. Annotation of 5-hydroxymethylcytosine genomic
      distribution reveal significant associations with RNA regulatory processes,
      immune function, stem cell maintenance and binding sites of transcription factors
      that drive cellular proliferation. In addition, model-based clustering results
      indicate that patients with low-5-hydroxymethylcytosine patterns have
      significantly poorer overall survival. Our results demonstrate that 5
      hydroxymethylcytosine patterns are strongly related with transcription, localizes
      to disease-critical genes and are associated with patient prognosis.

PMID- 27886175
TI  - Statistical power considerations in genotype-based recall randomized controlled
      trials.
AB  - Randomized controlled trials (RCT) are often underpowered for validating gene
      treatment interactions. Using published data from the Diabetes Prevention Program
      (DPP), we examined power in conventional and genotype-based recall (GBR) trials.
      We calculated sample size and statistical power for gene-metformin interactions
      (vs. placebo) using incidence rates, gene-drug interaction effect estimates and
      allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a
      metformin transported encoding locus. We then calculated statistical power for
      interactions between genetic risk scores (GRS), metformin treatment and intensive
      lifestyle intervention (ILI) given a range of sampling frames, clinical trial
      sample sizes, interaction effect estimates, and allele frequencies; outcomes were
      type 2 diabetes incidence (time-to-event) and change in small LDL particles
      (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR
      (participants recruited from the extremes of a GRS distribution) and conventional
      sampling (participants recruited without explicit emphasis on genetic
      characteristics). We further examined the influence of outcome measurement error
      on statistical power. Under most simulated scenarios, GBR trials have
      substantially higher power to observe gene-drug and gene-lifestyle interactions
      than same-sized conventional RCTs. GBR trials are becoming popular for validation
      of gene-treatment interactions; our analyses illustrate the strengths and
      weaknesses of this design.

PMID- 27886173
TI  - Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate
      genetic risk in inflammatory bowel disease.
AB  - Epigenetic alterations may provide important insights into gene-environment
      interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide
      DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls.
      These include 439 differentially methylated positions (DMPs) and 5 differentially
      methylated regions (DMRs), which we study in detail using whole genome bisulphite
      sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in
      an independent cohort. Using paired genetic and epigenetic data, we delineate
      methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with
      two polymorphisms in linkage disequilibrium with a known IBD susceptibility
      variant. Separated cell data shows that IBD-associated hypermethylation within
      the TXK promoter region negatively correlates with gene expression in whole-blood
      and CD8+ T cells, but not other cell types. Thus, site-specific DNA methylation
      changes in IBD relate to underlying genotype and associate with cell-specific
      alteration in gene expression.

PMID- 27886177
TI  - Work extraction from quantum systems with bounded fluctuations in work.
AB  - In the standard framework of thermodynamics, work is a random variable whose
      average is bounded by the change in free energy of the system. This average work
      is calculated without regard for the size of its fluctuations. Here we show that
      for some processes, such as reversible cooling, the fluctuations in work diverge.
      Realistic thermal machines may be unable to cope with arbitrarily large
      fluctuations. Hence, it is important to understand how thermodynamic efficiency
      rates are modified by bounding fluctuations. We quantify the work content and
      work of formation of arbitrary finite dimensional quantum states when the
      fluctuations in work are bounded by a given amount c. By varying c we interpolate
      between the standard and minimum free energies. We derive fundamental trade-offs
      between the magnitude of work and its fluctuations. As one application of these
      results, we derive the corrected Carnot efficiency of a qubit heat engine with
      bounded fluctuations.

PMID- 27886176
TI  - A feed-forward loop between lncARSR and YAP activity promotes expansion of renal
      tumour-initiating cells.
AB  - Renal tumour-initiating cells (T-ICs) contribute to tumorigenesis, progression
      and drug resistance of renal cell carcinoma (RCC). However, the underlying
      mechanism for the propagation of renal T-ICs remains unclear. Here we show that
      long non-coding RNA lncARSR is upregulated in primary renal T-ICs and associated
      with a poor prognosis of clear cell RCCs (ccRCC). Knockdown of lncARSR attenuates
      the self-renewal, tumorigenicity and metastasis of renal T-ICs. Conversely,
      forced lncARSR expression enhances T-IC properties of RCC cells. Mechanistically,
      the binding of lncARSR to YAP impedes LATS1-induced YAP phosphorylation and
      facilitates YAP nuclear translocation. Reciprocally, YAP/TEAD promotes lncARSR
      transcription, thus forming a feed-forward circuit. The correlation between
      lncARSR and YAP is validated in a ccRCC cohort, where the combination of these
      two parameters exhibits improved prognostic accuracy. Our findings indicate that
      lncARSR plays a critical role in renal T-ICs propagation and may serve as a
      prognostic biomarker and potential therapeutic target.

PMID- 27886178
TI  - A stable lithium-rich surface structure for lithium-rich layered cathode
      materials.
AB  - Lithium ion batteries are encountering ever-growing demand for further increases
      in energy density. Li-rich layered oxides are considered a feasible solution to
      meet this demand because their specific capacities often surpass 200 mAh g-1 due
      to the additional lithium occupation in the transition metal layers. However,
      this lithium arrangement, in turn, triggers cation mixing with the transition
      metals, causing phase transitions during cycling and loss of reversible capacity.
      Here we report a Li-rich layered surface bearing a consistent framework with the
      host, in which nickel is regularly arranged between the transition metal layers.
      This surface structure mitigates unwanted phase transitions, improving the
      cycling stability. This surface modification enables a reversible capacity of
      218.3 mAh g-1 at 1C (250 mA g-1) with improved cycle retention (94.1% after 100
      cycles). The present surface design can be applied to various battery electrodes
      that suffer from structural degradations propagating from the surface.

PMID- 27886179
TI  - Astrocytic GABA transporter activity modulates excitatory neurotransmission.
AB  - Astrocytes are ideally placed to detect and respond to network activity. They
      express ionotropic and metabotropic receptors, and can release gliotransmitters.
      Astrocytes also express transporters that regulate the extracellular
      concentration of neurotransmitters. Here we report a previously unrecognized role
      for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in
      astrocytic Na+ concentrations and a consequent increase in astrocytic Ca2+
      through Na+/Ca2+ exchange. This leads to the release of ATP/adenosine by
      astrocytes, which then diffusely inhibits neuronal glutamate release via
      activation of presynaptic adenosine receptors. Through this mechanism, increases
      in astrocytic GAT-3 activity due to GABA released from interneurons contribute to
      'diffuse' heterosynaptic depression. This provides a mechanism for homeostatic
      regulation of excitatory transmission in the hippocampus.

PMID- 27886180
TI  - MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment.
AB  - Rather than targeting tumour cells directly, elements of the tumour
      microenvironment can be modulated to sensitize tumours to the effects of therapy.
      Here we report a unique mechanism by which ectopic microRNA-103 can manipulate
      tumour-associated endothelial cells to enhance tumour cell death. Using gain-and
      loss of function approaches, we show that miR-103 exacerbates DNA damage and
      inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted
      delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour
      growth. Mechanistically, miR-103 regulation of its target gene TREX1 in
      endothelial cells governs the secretion of pro-inflammatory cytokines into the
      tumour microenvironment. Our data suggest that this inflammatory milieu may
      potentiate tumour cell death by supporting immune activation and inducing tumour
      expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk
      between vasculature and tumour cells that can be exploited to improve the
      efficacy of chemotherapy and radiation.

PMID- 27886181
TI  - A redox mechanism underlying nucleolar stress sensing by nucleophosmin.
AB  - The nucleolus has been recently described as a stress sensor. The nucleoplasmic
      translocation of nucleolar protein nucleophosmin (NPM1) is a hallmark of
      nucleolar stress; however, the causes of this translocation and its connection to
      p53 activation are unclear. Using single live-cell imaging and the redox
      biosensors, we demonstrate that nucleolar oxidation is a general response to
      various cellular stresses. During nucleolar oxidation, NPM1 undergoes S
      glutathionylation on cysteine 275, which triggers the dissociation of NPM1 from
      nucleolar nucleic acids. The C275S mutant NPM1, unable to be glutathionylated,
      remains in the nucleolus under nucleolar stress. Compared with wild-type NPM1
      that can disrupt the p53-HDM2 interaction, the C275S mutant greatly compromises
      the activation of p53, highlighting that nucleoplasmic translocation of NPM1 is a
      prerequisite for stress-induced activation of p53. This study elucidates a redox
      mechanism for the nucleolar stress sensing and may help the development of
      therapeutic strategies.

PMID- 27886182
TI  - Vitreous levels of placental growth factor correlate with activity of
      proliferative diabetic retinopathy and are not influenced by bevacizumab
      treatment.
AB  - PurposePlacental growth factor (PlGF) is a member of the VEGF family that plays
      an important role in experimental models of diabetic retinopathy and retinal
      neovascularization. We aimed to investigate whether vitreous levels of PlGF
      correlated with proliferative diabetic retinopathy (PDR) status, VEGF levels, and
      bevacizumab treatment. We also analysed PDR membranes to confirm the presence of
      the PlGF receptor, FLT1, in endothelial cells.MethodsThis was a case-control
      study: undiluted vitreous fluid samples were obtained from 28 active PDR patients
      without preoperative bevacizumab treatment, 21 active PDR patients with
      preoperative bevacizumab treatment, 18 inactive PDR patients, and 21 control
      patients. PlGF and VEGF levels in samples were determined by enzyme-linked
      immunosorbent assay. Immunohistochemistry for FLT1 was performed on human PDR
      membranes.ResultsCompared to control, vitreous PlGF levels were higher in both
      active PDR without bevacizumab (P<0.0001) and with bevacizumab (P<0.0001). There
      was no significant difference in PlGF between active PDR patients without and
      with bevacizumab (P=0.56). Compared to active PDR, PlGF levels were significantly
      reduced in inactive PDR (P=0.004). PlGF levels were highly correlated with VEGF
      levels in active PDR. VEGFR1 was expressed in endothelial cells in human PDR
      membranes.ConclusionThe strong correlation of PlGF levels with PDR disease status
      and expression of FLT1 in human PDR membranes suggest that PlGF has a pathogenic
      role in proliferative diabetic retinopathy. Therapeutic targeting of PlGF with
      agents like aflibercept may be beneficial.

PMID- 27886183
TI  - Fingolimod: therapeutic mechanisms and ocular adverse effects.
AB  - Fingolimod is an oral immunomodulating drug used in the management of relapsing
      remitting multiple sclerosis (RRMS). We aim to review the published literature on
      ocular manifestations of fingolimod therapy and their possible underlying
      mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine
      receptors, which are found ubiquitously in various organs, including lymphoid
      cells, central nervous system, cardiac myocytes, and smooth muscle cells.
      Fingolimod-associated macular oedema (FAME) is the most common ocular side effect
      but retinal haemorrhages and retinal vein occlusion can occur. The visual
      consequences appear to be mild and, in cases of FAME, resolution is often
      attained with discontinuation of therapy. However, in cases of retinal vein
      occlusion, discontinuation of fingolimod alone may not be sufficient and intra
      vitreal therapy may be required. We also propose a pragmatic service pathway for
      monitoring patients on fingolimod therapy, which includes stratifying them by
      risk and visual acuity.

PMID- 27886184
TI  - A view of the current and future role of optical coherence tomography in the
      management of age-related macular degeneration.
AB  - Optical coherence tomography (OCT) has become an established diagnostic
      technology in the clinical management of age-related macular degeneration (AMD).
      OCT is being used for primary diagnosis, evaluation of therapeutic efficacy, and
      long-term monitoring. Computer-based advances in image analysis provide
      complementary imaging tools such as OCT angiography, further novel automated
      analysis methods as well as feature detection and prediction of prognosis in
      disease and therapy by machine learning. In early AMD, pathognomonic features
      such as drusen, pseudodrusen, and abnormalities of the retinal pigment epithelium
      (RPE) can be imaged in a qualitative and quantitative way to identify early signs
      of disease activity and define the risk of progression. In advanced AMD, disease
      activity can be monitored clearly by qualitative and quantified analyses of fluid
      pooling, such as intraretinal cystoid fluid, subretinal fluid, and pigment
      epithelial detachment (PED). Moreover, machine learning methods detect a large
      spectrum of new biomarkers. Evaluation of treatment efficacy and definition of
      optimal therapeutic regimens are an important aim in managing neovascular AMD. In
      atrophic AMD hallmarked by geographic atrophy (GA), advanced spectral domain (SD)
      OCT imaging largely replaces conventional fundus autofluorescence (FAF) as it
      adds insight into the condition of the neurosensory layers and associated
      alterations at the level of the RPE and choroid. Exploration of imaging features
      by computerized methods has just begun but has already opened relevant and
      reliable horizons for the optimal use of OCT imaging for individualized and
      population-based management of AMD-the leading retinal epidemic of modern times.

PMID- 27886185
TI  - Hyper-IL-6: a potent and efficacious stimulator of RGC regeneration.
AB  - Mature retinal ganglion cells (RGCs) normally fail to regenerate injured axons
      and die soon after optic nerve injury. Research over the last two decades has
      demonstrated that application of IL-6-like cytokines or activation of respective
      downstream signaling pathways promote neuroprotection and optic nerve
      regeneration. However, the overall beneficial effects of natural cytokines remain
      usually rather moderate, possibly due to intrinsic signaling pathway inhibitors,
      such as PTEN or SOCS3, or a limited expression of specific cytokine receptors in
      RGCs. It was recently demonstrated that directly targeting the gp130 receptor, a
      common signalling receptor of all IL-6-like cytokines, induces stronger RGC axon
      regeneration in vitro and in vivo than other known growth-promoting treatments
      such as inflammatory stimulation or PTEN knockout. Remarkably, continuous
      expression of hyper-IL-6 (hIL-6) upon intravitreal AAV injection after nerve
      injury enables long-distance axon regeneration, with some axons growing through
      the optic chiasm 6 weeks after optic nerve injury. Thus, AAV-mediated hIL-6
      delivery is so far one of the strongest single, post-injury treatments for the
      promotion of optic nerve regeneration and may be suitable for the development of
      novel, clinically applicable therapeutic treatments for human patients.

PMID- 27886187
TI  - Plasma Proteomic Study in Pulmonary Arterial Hypertension Associated with
      Congenital Heart Diseases.
AB  - Pulmonary arterial hypertension associated with congenital heart disease (CHD
      PAH) has serious consequence and plasma protein profiles in CHD-PAH are unknown.
      We aimed to reveal the differential plasma proteins in 272 CHD patients with or
      without PAH. Various types of CHD-PAH were studied. Differential plasma proteins
      were first detected by iTRAQ proteomic technology and those with significant
      clinical relevance were selected for further ELISA validation in new cohort of
      patients. Among the 190 differential plasma proteins detected by iTRAQ, carbamoyl
      phosphate synthetase I (CPSI, related to urea cycle and endogenous nitric oxide
      production) and complement factor H-related protein 2 (CFHR2, related to
      complement system and coagulant mechanism) were selected for further ELISA
      validation in new cohort of 152 patients. Both CPSI and CFHR2 were down-regulated
      with decreased plasma levels (p < 0.01). Thus, we for the first time in CHD-PAH
      patients identified a large number of differential plasma proteins. The decreased
      CPSI expression in CHD-PAH patients may reveal a mechanism related to endogenous
      nitric oxide and the decrease of CFHR2 protein may demonstrate the deficiency of
      the immune system and coagulation mechanism. The findings may open a new
      direction for translational medicine in CHD-PAH with regard to the diagnosis and
      progress of the disease.

PMID- 27886189
TI  - Demonstration of a chip-based optical isolator with parametric amplification.
AB  - Despite being fundamentally challenging in integrated (nano)photonics, achieving
      chip-based light non-reciprocity becomes increasingly urgent in signal processing
      and optical communications. Because of material incompatibilities in conventional
      approaches based on the Faraday effect, alternative solutions have resorted to
      nonlinear processes to obtain one-way transmission. However, dynamic reciprocity
      in a recent theoretical analysis has pinned down the functionalities of these
      nonlinear isolators. To bypass such dynamic reciprocity, we here demonstrate an
      optical isolator on a silicon chip enforced by phase-matched parametric
      amplification in four-wave mixing. Using a high-Q microtoroid resonator, we
      realize highly non-reciprocal transport at the 1,550 nm wavelength when waves are
      injected from both directions in two different operating configurations. Our
      design, compatible with current complementary metal-oxide-semiconductor (CMOS)
      techniques, yields convincing isolation performance with sufficiently low
      insertion loss for a wide range of input power levels. Moreover, our work
      demonstrates the possibility of designing chip-based magnetic-free optical
      isolators for information processing and laser protection.

PMID- 27886190
TI  - Dysbiosis is not an answer.

PMID- 27886186
TI  - Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF
      kappaB and osteosarcoma progression.
AB  - The ability of cancer cells to survive and grow in anchorage- and serum
      independent conditions is well correlated with their aggressiveness. Here, using
      a human whole-genome shRNA library, we identify TMIGD3 isoform1 (i1) as a factor
      that suppresses this ability in osteosarcoma (OS) cells, mainly by inhibiting NF
      kappaB activity. Knockdown of TMIGD3 increases proliferation, tumour formation
      and metastasis of OS cells. Overexpression of TMIGD3 isoform1 (i1), but not
      isoform3 (i3) which shares a common C-terminal region, suppresses these malignant
      properties. Adenosine A3 receptor (A3AR) having an identical N-terminal region
      shows similar biological profiles to TMIGD3 i1. Protein expression of TMIGD3 and
      A3AR is lower in human OS tissues than normal tissues. Mechanistically, TMIGD3 i1
      and A3AR commonly inhibit the PKA-Akt-NF-kappaB axis. However, TMIGD3 i1 only
      partially rescues phenotypes induced by A3AR knockdown, suggesting the presence
      of distinct pathways. Our findings reveal an unappreciated role for TMIGD3 i1 as
      a suppressor of NF-kappaB activity and OS progression.

PMID- 27886188
TI  - The deubiquitinase USP21 maintains the stemness of mouse embryonic stem cells via
      stabilization of Nanog.
AB  - Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable
      expression of Nanog is essential to maintain the stemness of ESCs. However, Nanog
      is a short-lived protein and quickly degraded by the ubiquitin-dependent
      proteasome system. Here we report that the deubiquitinase USP21 interacts with,
      deubiquitinates and stabilizes Nanog, and therefore maintains the protein level
      of Nanog in mouse ESCs (mESCs). Loss of USP21 results in Nanog degradation, mESCs
      differentiation and reduces somatic cell reprogramming efficiency. USP21 is a
      transcriptional target of the LIF/STAT3 pathway and is downregulated upon
      differentiation. Moreover, differentiation cues promote ERK-mediated
      phosphorylation and dissociation of USP21 from Nanog, thus leading to Nanog
      degradation. In addition, USP21 is recruited to gene promoters by Nanog to
      deubiquitinate histone H2A at K119 and thus facilitates Nanog-mediated gene
      expression. Together, our findings provide a regulatory mechanism by which
      extrinsic signals regulate mESC fate via deubiquitinating Nanog.

PMID- 27886191
TI  - Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in
      hypoxic newborn pigs.
AB  - BACKGROUND: The aim of our study was to measure drug-related changes in
      hemodynamics and oxygen metabolism in response to different doses of an age
      appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to
      validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for
      subsequent clinical trials of this formulation in humans. METHODS: Newborn pigs
      (n = 18) were exposed to 2-h hypoxia (10-15% oxygen) followed by reoxygenation
      (21-30% oxygen 4 h). After 1-h reoxygenation, pigs were randomized to: control
      group (no treatment), dobutamine infusion at a rate of 10-15 or 15-20 ug/kg/min.
      Dobutamine groups received two dobutamine doses during 30 min with a 60 min
      washout period between doses. Cardiovascular profile and oxygen metabolism were
      monitored. In four animals, an ultrasonic perivascular flow probe was placed
      around superior vena cava to measure SVCF. RESULTS: Hypoxia significantly
      decreased CI, systemic vascular resistance and mean arterial blood pressure
      (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen
      delivery without changes in stroke-volume and MABP. Only 10-15 ug/kg/min
      increased oxygen consumption and peripheral tissue oxygenation measured by Near
      infrared spectroscopy. A positive correlation was observed between SVCF and CI.
      CONCLUSION: The new pediatric dobutamine formulation improved hemodynamic status,
      with dose-specific differences in metabolic response. SVCF may be a useful
      surrogate for CI in subsequent clinical trials.

PMID- 27886193
TI  - Antimicrobials: Constraints on microbial warfare.

PMID- 27886192
TI  - Phytanic acid attenuates insulin-like growth factor-1 activity via nitric oxide
      mediated gamma-secretase activation in rat aortic smooth muscle cells: possible
      implications for pathogenesis of infantile Refsum disease.
AB  - BACKGROUND: Infantile Refsum disease (IRD), a peroxisomal disease with defective
      phytanic acid oxidation, causes neurological impairment and development delay.
      Insulin-like growth factor-1 (IGF-1) regulates child development and to
      understand molecular mechanism(s) of IRD, we examined the effect of phytanic acid
      (PA) on IGF-1 activity. METHODS: Bromodeoxyuridine (BrdU) incorporation was
      measured in rat aortic smooth muscle cell (SMC) cultures following treatment with
      fetal bovine serum (FBS), basic fibroblast growth factor (bFGF), platelet-derived
      growth factor (PDGF) or IGF-1 in the absence or presence of PA. Gene expression
      and protein contents of IGF-1 receptor (IGF-1R) and PDGF receptor (PDGFR) were
      examined using quantitative PCR and western blotting. RESULTS: PA inhibited
      mitogenic activities of FBS, PDGF and IGF-1 with more pronounced effect on IGF-1
      induced bromodeoxyuridine (BrdU) incorporation. Palmitic acid or lignoceric acids
      did not inhibit IGF-1 activity. PA had no effect on PDGFR mRNA/protein levels but
      markedly increased IGF-1R mRNA levels. PA and nitric oxide (NO) markedly
      decreased IGF-1R protein. L-NAME, a NO synthase inhibitor and DAPT, a gamma
      secretase inhibitor, alleviated PA-induced decrease in IGF-1R protein. Both PA
      and NO donor increased gamma-secretase activity which was alleviated by L-NAME.
      CONCLUSION: This study demonstrates that PA attenuates IGF-1 activity possibly
      through IGF-1R impairment and NO-mediated modulation of gamma-secretase activity.

PMID- 27886194
TI  - Simultaneous Faraday filtering of the Mollow triplet sidebands with the Cs-D1
      clock transition.
AB  - Hybrid quantum systems integrating semiconductor quantum dots (QDs) and atomic
      vapours become important building blocks for scalable quantum networks due to the
      complementary strengths of individual parts. QDs provide on-demand single-photon
      emission with near-unity indistinguishability comprising unprecedented brightness
      while atomic vapour systems provide ultra-precise frequency standards and promise
      long coherence times for the storage of qubits. Spectral filtering is one of the
      key components for the successful link between QD photons and atoms. Here we
      present a tailored Faraday anomalous dispersion optical filter based on the
      caesium-D1 transition for interfacing it with a resonantly pumped QD. The
      presented Faraday filter enables a narrow-bandwidth (Deltaomega=2pi * 1 GHz)
      simultaneous filtering of both Mollow triplet sidebands. This result opens the
      way to use QDs as sources of single as well as cascaded photons in photonic
      quantum networks aligned to the primary frequency standard of the caesium clock
      transition.

PMID- 27886195
TI  - Is LUCA a thermophilic progenote?

PMID- 27886196
TI  - Reply to 'Is LUCA a thermophilic progenote?'

PMID- 27886197
TI  - Bone: Gut microbiota promote bone growth via IGF1.

PMID- 27886198
TI  - Obesity: Fermentable carbohydrates increase satiety signals.

PMID- 27886199
TI  - Global warming-induced upper-ocean freshening and the intensification of super
      typhoons.
AB  - Super typhoons (STYs), intense tropical cyclones of the western North Pacific,
      rank among the most destructive natural hazards globally. The violent winds of
      these storms induce deep mixing of the upper ocean, resulting in strong sea
      surface cooling and making STYs highly sensitive to ocean density stratification.
      Although a few studies examined the potential impacts of changes in ocean thermal
      structure on future tropical cyclones, they did not take into account changes in
      near-surface salinity. Here, using a combination of observations and coupled
      climate model simulations, we show that freshening of the upper ocean, caused by
      greater rainfall in places where typhoons form, tends to intensify STYs by
      reducing their ability to cool the upper ocean. We further demonstrate that the
      strengthening effect of this freshening over the period 1961-2008 is ~53%
      stronger than the suppressive effect of temperature, whereas under twenty-first
      century projections, the positive effect of salinity is about half of the
      negative effect of ocean temperature changes.

PMID- 27886200
TI  - It takes a village.

PMID- 27886201
TI  - Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy.
AB  - HIV-associated cryptococcal meningitis is by far the most common cause of adult
      meningitis in many areas of the world that have high HIV seroprevalence. In most
      areas in Sub-Saharan Africa, the incidence of cryptococcal meningitis is not
      decreasing despite availability of antiretroviral therapy, because of issues of
      adherence and retention in HIV care. In addition, cryptococcal meningitis in HIV
      seronegative individuals is a substantial problem: the risk of cryptococcal
      infection is increased in transplant recipients and other individuals with
      defects in cell-mediated immunity, and cryptococcosis is also reported in the
      apparently immunocompetent. Despite therapy, mortality rates in these groups are
      high. Over the past 5 years, advances have been made in rapid point-of-care
      diagnosis and early detection of cryptococcal antigen in the blood. These
      advances have enabled development of screening and pre-emptive treatment
      strategies aimed at preventing the development of clinical infection in patients
      with late-stage HIV infection. Progress in optimizing antifungal combinations has
      been aided by evaluation of the clearance rate of infection by using serial
      quantitative cultures of cerebrospinal fluid (CSF). Measurement and management of
      raised CSF pressure, a common complication, is a vital component of care. In
      addition, we now better understand protective immune responses in HIV-associated
      cases, immunogenetic predisposition to infection, and the role of immune-mediated
      pathology in patients with non-HIV associated infection and in the context of HIV
      associated immune reconstitution reactions.

PMID- 27886202
TI  - Multiple sclerosis: New imaging marker of brain leukocyte infiltration.

PMID- 27886203
TI  - Stroke: CT identifies patients in stroke treatment window.

PMID- 27886204
TI  - Characterization of Structural Connectivity of the Default Mode Network in Dogs
      using Diffusion Tensor Imaging.
AB  - Diffusion tensor imaging (DTI) provides us an insight into the micro-architecture
      of white-matter tracts in the brain. This method has proved promising in
      understanding and investigating the neuronal tracts and structural connectivity
      between the brain regions in primates as well as rodents. The close evolutionary
      relationship between canines and humans may have spawned a unique bond in regard
      to social cognition rendering them useful as an animal model in translational
      research. In this study, we acquired diffusion data from anaesthetized dogs and
      created a DTI-based atlas for a canine model which could be used to investigate
      various white matter diseases. We illustrate the application of this atlas by
      calculating DTI tractography based structural connectivity between the anterior
      cingulate cortex (ACC) and posterior cingulate cortex (PCC) regions of the
      default mode network (DMN) in dogs. White matter connectivity was investigated to
      provide structural basis for the functional dissociation observed between the
      anterior and posterior parts of DMN. A comparison of the integrity of long range
      structural connections (such as in the DMN) between dogs and humans is likely to
      provide us with new perspectives on the neural basis of the evolution of
      cognitive functions.

PMID- 27886205
TI  - A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential.
AB  - Malignant mesothelioma (MM) is an aggressive serosal tumor associated with
      asbestos exposure. We previously demonstrated that mesothelial cells
      differentiate into cells of different mesenchymal lineages and hypothesize that
      osseous tissue observed in a subset of MM patients is due to local
      differentiation of MM cells. In this study, the capacity of human and mouse MM
      cells to differentiate into osteoblast-like cells was determined in vitro using a
      functional model of bone nodule formation and in vivo using an established model
      of MM. Human and murine MM cell lines cultured in osteogenic medium expressed
      alkaline phosphatase and formed mineralized bone-like nodules. Several human and
      mouse MM cell lines also expressed a number of osteoblast phenotype markers,
      including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin
      and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors
      identified areas of ossification within the tumor, similar to those observed in
      human MM biopsies. These data demonstrate the ability of MM to differentiate into
      another mesenchymal cell type and suggest that MM cells may contribute to the
      formation of the heterologous elements observed in MM tumors.

PMID- 27886207
TI  - Characteristic tetrapod musculoskeletal limb phenotype emerged more than 400 MYA
      in basal lobe-finned fishes.
AB  - Previous accounts of the origin of tetrapod limbs have postulated a relatively
      sudden change, after the split between extant lobe-finned fish and tetrapods,
      from a very simple fin phenotype with only two muscles to the highly complex
      tetrapod condition. The evolutionary changes that led to the muscular anatomy of
      tetrapod limbs have therefore remained relatively unexplored. We performed
      dissections, histological sections, and MRI scans of the closest living relatives
      of tetrapods: coelacanths and lungfish. Combined with previous comparative,
      developmental and paleontological information, our findings suggest that the
      characteristic tetrapod musculoskeletal limb phenotype was already present in the
      Silurian last common ancestor of extant sarcopterygians, with the exception of
      the autopod (hand/foot) structures, which have no clear correspondence with fish
      structures. Remarkably, the two major steps in this long process - leading to the
      ancestral fin anatomy of extant sarcopterygians and limb anatomy of extant
      tetrapods, respectively - occurred at the same nodes as the two major similarity
      bottlenecks that led to the striking derived myological similarity between the
      pectoral and pelvic appendages within each taxon. Our identification of probable
      homologies between appendicular muscles of sarcopterygian fish and tetrapods will
      allow more detailed reconstructions of muscle anatomy in early tetrapods and
      their relatives.

PMID- 27886208
TI  - Flexible controls of scattering clouds using coding metasurfaces.
AB  - Metamaterials or metasurfaces have been designed to precisely manipulate the
      scattering at every angle. Here, we propose to control the probability of random
      scattering appearing in the desired range of angles, which is defined in this
      letter as scattering cloud. We present a controllable random metasurface by
      simply adding a random coding sequence to gradient coding sequence. It is shown
      that the direction and size of the scattering cloud can be arbitrarily
      engineered. We demonstrate the exotic behavior of the scattering cloud by making
      an analogy to the electron cloud in quantum mechanics. A new coding particle
      featuring low-interference with neighboring coding particles is designed to
      realize the controllable random surface, which demonstrates highly consistent
      results to the theoretical calculations using fast Fourier transform. The
      exciting phenomena and versatile behaviors of scattering clouds and their
      probabilities enabled by controllable random surfaces will lead to diversified
      applications in the fields of electromagnetic waves and acoustic waves.

PMID- 27886206
TI  - The antidepressant-like activity of AC-5216, a ligand for 18KDa translocator
      protein (TSPO), in an animal model of diabetes mellitus.
AB  - Diabetes mellitus is a chronic disease that is associated with depression. Also,
      depression is common in adults with type 2 diabetes mellitus (T2DM). Translocator
      protein (18kDa) (TSPO) and allopregnanolone play an important role in the
      depression treatment. However, few studies have evaluated TSPO and
      allopregnanolone in the treatment of depression in T2DM. AC-5216, a ligand for
      TSPO, produces anxiolytic- and antidepressant-like effects in animal models. The
      present study aimed to explore antidepressant-like effects of AC-5216 on diabetic
      rats. Following the development of diabetic model induced by high fat diet (HFD)
      feeding and streptozotocin (STZ), AC-5216 (0.3 and 1 mg/kg, i.g.) elicited the
      antidepressant-like effects in behavioral tests while these activities were
      blocked by TSPO antagonist PK11195 (3 mg/kg, i.p.). The levels of
      allopregnanolone in the prefrontal cortex and hippocampus were increased by AC
      5216 (0.3 and 1 mg/kg, i.g.), which was antagonized by PK11195 (3 mg/kg, i.p.).
      The increased plasma glucose (PG) and decreased insulin (INS) in HFD-STZ rats
      were reversed by AC-5216 (0.3 and 1 mg/kg, i.g.). This study indicates that the
      antidepressant-like effects of AC-5216 on HFD-STZ rats, suggesting that TSPO may
      represent a novel therapeutic target for depression in T2DM.

PMID- 27886209
TI  - Virus infection drives IL-2 antibody complexes into pro-inflammatory agonists in
      mice.
AB  - The use of IL-2/JES6-1 Ab complex (IL-2 Ab Cx) has been considered as a potential
      therapeutic for inflammatory diseases due to its selective expansion of
      regulatory T cells (Tregs) in mice. Here, IL-2 Ab Cx was explored as a
      therapeutic agent to reduce joint inflammation induced by chikungunya virus, an
      alphavirus causing debilitating joint disease globally. Virus-infected mice
      treated with IL-2 Ab Cx exhibited exacerbated joint inflammation due to
      infiltration of highly activated CD4+ effector T cells (Teffs). Virus infection
      led to upregulation of CD25 on the Teffs, rendering them sensitive towards IL2 Ab
      Cx. Ready responsiveness of Teffs to IL-2 was further demonstrated in healthy
      human donors, suggesting that the use of IL-2 Ab Cx in humans is not suitable.
      Changes in IL-2 sensitivity during active virus infection could change the
      responsive pattern towards the IL-2 Ab Cx, resulting in the expansion of pro
      inflammatory rather than anti-inflammatory responses.

PMID- 27886211
TI  - Ultrathin Co-O oxide layer-driven perpendicular magnetic anisotropy in a
      CoO/[Co/Pd]m multilayer matrix upon annealing.
AB  - Ferromagnetic/noble metal multilayer (ML) frames are expected to serve as
      reliable building blocks in a variety of perpendicular magnetic anisotropy (PMA)
      based spintronic devices. However, ultrathin ML matrices are highly susceptible
      to unintended reduction of electron spin polarization in the as-grown or annealed
      states and often require a large repeat number. Here, we introduce a simple
      approach to achieve thermally stable PMA in ultrathin [Co/Pd]3 MLs involving the
      incorporation of an ultrathin CoO capping layer. The thickness and oxygen content
      of the CoO layer are critical parameters to achieve enhanced PMA in ultrathin
      [Co/Pd]3/CoO MLs post-annealed up to 400  degrees C. An extensive analysis of
      structural features identified that robust PMA characteristics in [Co/Pd]3/CoO
      MLs are linked with thermally activated oxygen atom diffusion leading to
      structural reconfiguration upon annealing. The possible origin of the enhanced
      PMA in our [Co/Pd]3/CoO ML samples after high-temperature annealing is discussed,
      thereby enabling their use in future spintronic-related devices.

PMID- 27886210
TI  - Physical Activity, Energy Expenditure, and Defense of Body Weight in Melanocortin
      4 Receptor-Deficient Male Rats.
AB  - Melanocortin 4 receptor (MC4R) variants contribute to human obesity, and rats
      lacking functional MC4R (Mc4rK314X/K314X) are obese. We investigated the
      hypothesis that low energy expenditure (EE) and physical activity contribute to
      this obese phenotype in male rats, and determined whether lack of functional MC4R
      conferred protection from weight loss during 50% calorie restriction. Though
      Mc4rK314X/K314X rats showed low brown adipose Ucp1 expression and were less
      physically active than rats heterozygous for the mutation (Mc4r+/K314X) or wild
      type (Mc4r+/+) rats, we found no evidence of lowered EE in Mc4rK314X/K314X rats
      once body weight was taken into account using covariance. Mc4rK314X/K314X rats
      had a significantly higher respiratory exchange ratio. Compared to Mc4r+/+ rats,
      Mc4rK314X/K314X and Mc4r+/K314X rats lost less lean mass during calorie
      restriction, and less body mass when baseline weight was accounted for. Limited
      regional overexpression of Mc3r was found in the hypothalamus. Although lower
      physical activity levels in rats with nonfunctional MC4R did not result in lower
      total EE during free-fed conditions, rats lacking one or two functional copies of
      Mc4r showed conservation of mass, particularly lean mass, during energy
      restriction. This suggests that variants affecting MC4R function may contribute
      to individual differences in the metabolic response to food restriction.

PMID- 27886213
TI  - Promotive effects of bone morphogenetic protein 2 on angiogenesis in
      hepatocarcinoma via multiple signal pathways.
AB  - The effects of Bone morphogenetic protein 2 (BMP-2) on the angiogenesis of
      hepatocellular carcinoma have not yet been observed and its molecular mechanisms
      is not clear. We first constructed the recombinant lentivirus vectors expressing
      small hairpin RNA against BMP-2 gene (LV-SH-BMP2) and the recombinant lentivirus
      vectors over-expressing BMP-2 (overexpression-LV-BMP2), and then the two
      recombinant lentivirus vectors were respectively transfected into Hep G2 cells.
      The Hep G2 cells transfected with LV-SH-BMP2 or overexpression-LV-BMP2 were
      respectively co-cultured with human umbilical vein endothelial cells (HUVECs) to
      observe the effects of BMP-2 on HUVECs. The effect of BMP-2 on tumor microvessel
      density (MVD) was examined. The abilities of proliferation, migration and
      angiogenesis were significantly inhibited in the HUVECs co-cultured with BMP-2
      knockdown Hep G2 (all P < 0.05), but significantly enhanced in the HUVECs co
      cultured with BMP-2 overexpression Hep G2 (all P < 0.05). MVD was significantly
      increased in overexpression-LV-BMP2-transfected Hep G2 tumor, but decreased in LV
      SH-BMP2-transfected Hep G2 tumors. The protein expressions of VEGF, p-P38, p-ERK,
      p-AKT, p-m-TOR were significantly increased after BMP-2 over-expression, or
      significantly decreased after BMP-2 knockdown (all P < 0.05). These results
      reveal that BMP-2 can enhance HUVEC proliferation, migration and angiogenesis
      through P38, ERK and Akt/m-TOR pathway.

PMID- 27886212
TI  - Structural and Functional Connectivity of Default Mode Network underlying the
      Cognitive Impairment in Late-onset Depression.
AB  - To identify the association between the functional and structural changes of
      default mode network (DMN) underlying the cognitive impairment in Late-onset
      depression (LOD), 32 LOD patients and 39 normal controls were recruited and
      underwent resting-state fMRI, DTI scans, and cognitive assessments. Seed-based
      correlation analysis was conducted to explore the functional connectivity (FC) of
      the DMN. Deterministic tractography between FC-impaired regions was performed to
      examine the structural connectivity (SC). Partial correlation analyses were
      employed to evaluate the cognitive association of those altered FC and SC.
      Compared with controls, LOD patients showed decreased FC between DMN and the
      cingulo-opercular network (CON), as well as the thalamus. Decreased FA and
      increased RD of these fiber tracts connecting DMN with CON were found in LOD
      patient. The DMN-CON FC and the FA, RD of the fiber tracts were both
      significantly correlated with the cognitive performance. Therefore, the cognitive
      impairment in LOD might be associated with the decreased FC between the DMN and
      the CON, which probably resulted from the demyelination of the white matter.

PMID- 27886215
TI  - Hyperinvasiveness of Salmonella enterica serovar Choleraesuis linked to
      hyperexpression of type III secretion systems in vitro.
AB  - Salmonella enterica serovars Choleraesuis and Typhimurium are among the non
      typhoid Salmonella serovars that are important zoonotic pathogens. In clinical
      observation, S. Typhimurium typically causes diarrheal diseases; however, S.
      Choleraesuis shows high predilection to cause bacteremia. The mechanism why S.
      Choleraesuis is more invasive to humans remains unknown. In this study, we
      compared the S. Typhimurium LT2 and S. Choleraesuis SC-B67 proteomes through
      stable isotope labeling of amino acid in cell culture (SILAC). In SILAC, the
      expression of many virulence proteins in two type III secretion systems (T3SSs)
      were significantly higher in S. Choleraesuis than in S. Typhimurium. Similar
      differences were also found at the transcriptional level. Compared to S.
      Typhimurium, S. Choleraesuis showed a higher penetration level to Caco-2 (>100
      fold) and MDCK (>10-fold) monolayers. In mice after oral challenge, the invasion
      of spleen and liver was also higher in S. Choleraesuis than in S. Typhimurium.
      The transcription of hilD in S. Choleraesuis was increased in physiological (1
      mM) or high (10 mM) concentrations of Mg2+, but not in low (8 MUM) concentration.
      We conclude that S. Choleraesuis showed hyperinvasiveness in cellular as well as
      mouse models due to hyperexpression of T3SS genes.

PMID- 27886216
TI  - Drought rapidly diminishes the large net CO2 uptake in 2011 over semi-arid
      Australia.
AB  - Each year, terrestrial ecosystems absorb more than a quarter of the anthropogenic
      carbon emissions, termed as land carbon sink. An exceptionally large land carbon
      sink anomaly was recorded in 2011, of which more than half was attributed to
      Australia. However, the persistence and spatially attribution of this carbon sink
      remain largely unknown. Here we conducted an observation-based study to
      characterize the Australian land carbon sink through the novel coupling of
      satellite retrievals of atmospheric CO2 and photosynthesis and in-situ flux tower
      measures. We show the 2010-11 carbon sink was primarily ascribed to savannas and
      grasslands. When all biomes were normalized by rainfall, shrublands however, were
      most efficient in absorbing carbon. We found the 2010-11 net CO2 uptake was
      highly transient with rapid dissipation through drought. The size of the 2010-11
      carbon sink over Australia (0.97 Pg) was reduced to 0.48 Pg in 2011-12, and was
      nearly eliminated in 2012-13 (0.08 Pg). We further report evidence of an earlier
      2000-01 large net CO2 uptake, demonstrating a repetitive nature of this land
      carbon sink. Given a significant increasing trend in extreme wet year
      precipitation over Australia, we suggest that carbon sink episodes will exert
      greater future impacts on global carbon cycle.

PMID- 27886217
TI  - A Facile Methodology for Engineering the Morphology of CsPbX3 Perovskite
      Nanocrystals under Ambient Condition.
AB  - A facile and highly reproducible room temperature, open atmosphere synthesis of
      cesium lead halide perovskite nanocrystals of six different morphologies is
      reported just by varying the solvent, ligand and reaction time. Sequential
      evolution of the quantum dots, nanoplates and nanobars in one medium and
      nanocubes, nanorods and nanowires in another medium is demonstrated. These
      perovskite nanoparticles are shown to be of excellent crystalline quality with
      high fluorescence quantum yield. A mechanism of the formation of nanoparticles of
      different shapes and sizes is proposed. Considering the key role of morphology in
      nanotechnology, this simple method of fabrication of a wide range of high quality
      nanocrystals of different shapes and sizes of all-inorganic lead halide
      perovskites, whose potential is already demonstrated in light emitting and
      photovoltaic applications, is likely to help widening the scope and utility of
      these materials in optoelectronic devices.

PMID- 27886214
TI  - Epigenetic Enhancement of the Post-replicative DNA Mismatch Repair of Mammalian
      Genomes by a Hemi-mCpG-Np95-Dnmt1 Axis.
AB  - DNA methylation at C of CpG dyads (mCpG) in vertebrate genomes is essential for
      gene regulation, genome stability and development. We show in this study that
      proper functioning of post-replicative DNA mismatch repair (MMR) in mammalian
      cells relies on the presence of genomic mCpG, as well as on the maintenance DNA
      methyltransferase Dnmt1 independently of its catalytic activity. More
      importantly, high efficiency of mammalian MMR surveillance is achieved through a
      hemi-mCpG-Np95(Uhrf1)-Dnmt1 axis, in which the MMR surveillance complex(es) is
      recruited to post-replicative DNA by Dnmt1, requiring its interactions with
      MutSalpha, as well as with Np95 bound at the hemi-methylated CpG sites. Thus,
      efficiency of MMR surveillance over the mammalian genome in vivo is enhanced at
      the epigenetic level. This synergy endows vertebrate CpG methylation with a new
      biological significance and, consequently, an additional mechanism for the
      maintenance of vertebrate genome stability.

PMID- 27886218
TI  - Revisiting the fear of snakes in children: the role of aposematic signalling.
AB  - Why humans fear snakes is an old, yet unresolved debate. Its innate origin from
      evolutionary causes is debated against the powerful influence early experience,
      culture, media and religion may have on people's aversion to snakes. Here we show
      that the aversion to snakes in human beings may have been mistaken for an
      aversion to aposematic signals that are commonly displayed by snakes. A total of
      635 children were asked to rate single item images as "nice" or "mean". Snakes,
      pets and smiley emoticon items were not rated as "mean" unless they displayed
      subtle aposematic signals in the form of triangular (rather than round) shapes.
      Another 722 children were shown images featuring two items and asked which item
      was "nice" and which item was "mean". This context dependent comparison triggered
      even sharper responses to aposematic signals. We hypothesise that early primates
      evolved an aversion for aposematic signals in the form of potentially harmful
      triangular shapes such as teeth, claws or spikes, not for snakes per se. Further,
      we hypothesise that this adaptation was in turn exploited by snakes in their anti
      predatory threat display as a triangular head or dorsal zig-zag pattern, and is
      currently the basis for efficient international road-danger signalling.

PMID- 27886219
TI  - Elderly suicide trends in the context of transforming China, 1987-2014.
AB  - In the context of rapid ageing, understanding the time-trend of elderly suicide
      (ES) could inform China's efforts on suicide prevention. We examined time-trends
      in Chinese ES rates (ESRs) from 1987 to 2014, a period of profound social
      changes. Suicide rates by residence (rural/urban), gender, and 5-year age-group
      (65+) in 1987-2014 were provided by the Chinese Ministry of Health. Time-trends
      were analyzed with joinpoint analysis. The time-trend of national ESRs was
      downward (average annual percent change [AAPC] = -3.7, P < 0.001): 76.6/100000 in
      1987 and 30.2/100000 in 2014. However, the time-trend of corresponding
      percentages of ESs among the total suicides was monotonically increasing (AAPC =
      3.4, P < 0.001): 16.9% in 1987 to 41.2% in 2014. The time-trends in ESRs of both
      rural and urban men and women were decreasing, but only the rural trends were
      significant (P < 0.001). Rural-urban and male-female differences in ESRs were
      decreasing over time (slope = -4.2 and -3.0, P <= 0.006), but the rural-urban and
      male-female ESR differences in 2014 remained large (16.3/100000 and 9.8/100000, P
      < 0.001). While national ESRs decreased significantly during the past three
      decades, the current ESR remains high in China. Further, the age-pattern of
      Chinese suicide is transitioning to elderly predominance. ES, particularly rural
      ES, should be a public health priority in China.

PMID- 27886220
TI  - Tuning the Weak Ferromagnetic States in Dysprosium Orthoferrite.
AB  - RFeO3 orthoferrites, where R is a rare-earth ion of the lanthanide series, are
      attracting attention mostly because of their promising fast spin dynamics. The
      magnetic properties of these materials seem to crucially depend on whether the
      magnetizations of the R and Fe ions' weak ferromagnetic (WFM) components are
      parallel or antiparallel to each other. Here, we report an extensive
      investigation of a high-quality DyFeO3 single crystal in which the induced Dy3+
      magnetization (FDy) has a natural tendency to be antiparallel to Fe3+ sublattice
      magnetization (FFe) within a large temperature window. Moreover, we find that
      specific variations of temperature and applied magnetic fields allow us to make
      FDy parallel to FFe, or force a spin-flip transition in FFe, among other effects.
      We found three different magnetic states that respond to temperature and magnetic
      fields, i.e. linear versus constant or, alternatively, presenting either behavior
      depending on the history of the sample. An original magnetic field-versus
      temperature phase diagram is constructed to indicate the region of stability of
      the different magnetic phases, and to reveal the precise conditions yielding
      sudden spin switching and reversals. Knowledge of such a phase diagram is of
      potential importance to applications in spintronics and magnetic devices.

PMID- 27886222
TI  - Visualising Berry phase and diabolical points in a quantum exciton-polariton
      billiard.
AB  - Diabolical points (spectral degeneracies) can naturally occur in spectra of two
      dimensional quantum systems and classical wave resonators due to simple
      symmetries. Geometric Berry phase is associated with these spectral degeneracies.
      Here, we demonstrate a diabolical point and the corresponding Berry phase in the
      spectrum of hybrid light-matter quasiparticles-exciton-polaritons in
      semiconductor microcavities. It is well known that sufficiently strong optical
      pumping can drive exciton-polaritons to quantum degeneracy, whereby they form a
      macroscopically populated quantum coherent state similar to a Bose-Einstein
      condensate. By pumping a microcavity with a spatially structured light beam, we
      create a two-dimensional quantum billiard for the exciton-polariton condensate
      and demonstrate a diabolical point in the spectrum of the billiard eigenstates.
      The fully reconfigurable geometry of the potential walls controlled by the
      optical pump enables a striking experimental visualization of the Berry phase
      associated with the diabolical point. The Berry phase is observed and measured by
      direct imaging of the macroscopic exciton-polariton probability densities.

PMID- 27886221
TI  - Hydrocarbon degraders establish at the costs of microbial richness, abundance and
      keystone taxa after crude oil contamination in permafrost environments.
AB  - Oil spills from pipeline ruptures are a major source of terrestrial petroleum
      pollution in cold regions. However, our knowledge of the bacterial response to
      crude oil contamination in cold regions remains to be further expanded,
      especially in terms of community shifts and potential development of hydrocarbon
      degraders. In this study we investigated changes of microbial diversity,
      population size and keystone taxa in permafrost soils at four different sites
      along the China-Russia crude oil pipeline prior to and after perturbation with
      crude oil. We found that crude oil caused a decrease of cell numbers together
      with a reduction of the species richness and shifts in the dominant phylotypes,
      while bacterial community diversity was highly site-specific after exposure to
      crude oil, reflecting different environmental conditions. Keystone taxa that
      strongly co-occurred were found to form networks based on trophic interactions,
      that is co-metabolism regarding degradation of hydrocarbons (in contaminated
      samples) or syntrophic carbon cycling (in uncontaminated samples). With this
      study we demonstrate that after severe crude oil contamination a rapid
      establishment of endemic hydrocarbon degrading communities takes place under
      favorable temperature conditions. Therefore, both endemism and trophic
      correlations of bacterial degraders need to be considered in order to develop
      effective cleanup strategies.

PMID- 27886224
TI  - Intravitreal infusion: A novel approach for intraocular drug delivery.
AB  - Intraocular injection has become an increasingly important intervention in the
      treatment of posterior segment diseases. However, an acute intraocular pressure
      (IOP) elevation after intravitreal injection is a common concern. This study
      aimed to evaluate the efficacy of intravitreal infusion in maintaining stable IOP
      in a rabbit model. Trypan blue (TB) 0.06% with an external pump was used to
      evaluate intravitreal infusion in rabbit eyes. Groups A (50 MUL), B (100 MUL), C
      (150 MUL), and D (200 MUL) were slowly infused over 30 minutes with TB. As a
      control, Group E underwent conventional intravitreal injection of 100 MUL of TB.
      Group F received a bolus infusion of 100 MUL of TB within 1 minute. The mean
      increases in IOP during infusion for each group were: Group A (7.93 +/- 3.80
      mmHg), B (13.97 +/- 3.17 mmHg), C (19.91 +/- 6.06 mmHg) and D (29.38 +/- 8.97
      mmHg). Immediately post-injection in group E the mean increase in IOP amounted to
      34.33 +/- 6.57 mmHg. The mean increase in IOP of group F after bolus infusion was
      49.89 +/- 1.71 mmHg. Intravitreal infusion maintains a stable IOP and provides a
      controlled infusion speed compared with intravitreal injection.

PMID- 27886223
TI  - Redox cofactors insertion in prokaryotic molybdoenzymes occurs via a conserved
      folding mechanism.
AB  - A major gap of knowledge in metalloproteins is the identity of the prefolded
      state of the protein before cofactor insertion. This holds for molybdoenzymes
      serving multiple purposes for life, especially in energy harvesting. This large
      group of prokaryotic enzymes allows for coordination of molybdenum or tungsten
      cofactors (Mo/W-bisPGD) and Fe/S clusters. Here we report the structural data on
      a cofactor-less enzyme, the nitrate reductase respiratory complex and
      characterize the conformational changes accompanying Mo/W-bisPGD and Fe/S
      cofactors insertion. Identified conformational changes are shown to be essential
      for recognition of the dedicated chaperone involved in cofactors insertion. A
      solvent-exposed salt bridge is shown to play a key role in enzyme folding after
      cofactors insertion. Furthermore, this salt bridge is shown to be strictly
      conserved within this prokaryotic molybdoenzyme family as deduced from a
      phylogenetic analysis issued from 3D structure-guided multiple sequence
      alignment. A biochemical analysis with a distantly-related member of the family,
      respiratory complex I, confirmed the critical importance of the salt bridge for
      folding. Overall, our results point to a conserved cofactors insertion mechanism
      within the Mo/W-bisPGD family.

PMID- 27886225
TI  - No evidence of NRAS mutation in squamous cell anal carcinoma (SCAC).
AB  - Epidermal growth factor receptor (EGFR) is usually expressed in squamous cell
      anal carcinoma (SCAC) and anti-EGFR agents could represent a valid treatment
      strategy, also considering that KRAS and BRAF mutations are rare events in this
      type of cancer. However, no data are available on NRAS status in SCAC. In this
      study we analyzed NRAS status (exons 2-4) by Pyrosequencing in a case series of
      50 SCAC patients previously characterized in our laboratory for KRAS, BRAF,
      PIK3CA mutations and HPV and HIV infections. We found no mutation in NRAS gene.
      These results confirm that since the principal anti-EGFR resistance mechanisms
      are almost absent in SCAC, anti-EGFR agents should be considered for the
      treatment of this type of cancer.

PMID- 27886226
TI  - Functional Improvement and Regression of Medial Hypertrophy in the Remodeled
      Pulmonary Artery after Correction of Systemic Left-to-Right Shunt.
AB  - The presence of systemic left-to-right shunt and increased pulmonary blood flow
      can result in right heart failure and pulmonary arteriopathy. Correction of left
      to-right shunt has been shown to improve cardiac function and physical
      performance. However, the cardiopulmonary remodeling processes following
      cessation of left-to-right shunt have yet to be reported. In this experimental
      study, excessive pulmonary flow was restored through ligation of the aortocaval
      fistula in rats with flow-induced pulmonary hypertension. The cardiopulmonary
      morphometric functions were assessed, and phenotypic switching of pulmonary
      vascular smooth muscle cells (VSMC) was determined. Ligation of aortocaval
      fistula significantly attenuated pulmonary blood flow and right ventricular mass,
      and potentiated the isometric contraction of pulmonary artery. Inflammatory
      cytokines IL-1beta and IL-6 were reduced in the lung after ligation. Reduction of
      pulmonary blood flow restored the expressions of smooth muscle myosin heavy chain
      and alpha-smooth muscle actin in pulmonary artery, indicating the switching of
      VSMCs to the contractile phenotype. Our study demonstrated that normalization of
      pulmonary blood flow in flow-induced pulmonary hypertension reverses the
      remodeling in the right ventricle and pulmonary artery. The remodeling process of
      flow-induced pulmonary hypertension is functionally and morphometrically
      reversible by inducing transdifferentiation of pulmonary VSMC to contractile
      phenotypes and modulation of tissue inflammatory cytokines.

PMID- 27886227
TI  - Impact of human activities on subaqueous topographic change in Lingding Bay of
      the Pearl River estuary, China, during 1955-2013.
AB  - Estuaries have been sites of intensive human activities during the past century.
      Tracing the evolution of subaqueous topography in estuaries on a decadal
      timescale enables us to understand the effects of human activities on estuaries.
      Bathymetric data from 1955 to 2010 show that land reclamation decreased the
      subaqueous area of Lingding Bay, in the Pearl River estuary, by ~170 km2 and
      decreased its water volume by 615 * 106 m3, representing a net decrease of 11.2 *
      106 m3 per year and indicating the deposition of approximately 14.5 Mt/yr of
      sediment in Lingding Bay during that period. Whereas Lingding Bay was mainly
      governed by natural processes with slight net deposition before 1980, subsequent
      dredging and large port engineering projects changed the subaqueous topography of
      the bay by shallowing its shoals and deepening its troughs. Between 2012 and
      2013, continuous dredging and a surge of sand excavation resulted in local
      changes in water depth of +/- 5 m/yr, far exceeding the magnitude of natural
      topographic evolution in Lingding Bay. Reclamation, dredging, and navigation
      channel projects removed 8.4 Mt/yr of sediment from Lingding Bay, representing
      29% of the sediment input to the bay, and these activities have increased
      recently.

PMID- 27886229
TI  - Expanding and exploring the diversity of phytoplasmas from lucerne (Medicago
      sativa).
AB  - Phytoplasmas are a group of insect-vectored bacteria responsible for disease in
      many plant species worldwide. Among the crop species affected is the economically
      valuable forage species lucerne. Here we provide comprehensive molecular evidence
      for infection in multiple lucerne plants by a phytoplasma not previously known
      from this plant species. This phytoplasma had a >99% genetic similarity to an
      unclassified 16S rRNA subgroup previously reported as Stylosanthes little leaf
      from Stylosanthes spp. and was genetically and symptomatically distinct from a co
      occurring but less common 16SrIIA group phytoplasma. Neighbour-joining analyses
      with publicly available sequence data confirmed the presence of two distinct
      phytoplasma lineages in the plant population. No PCR detections were made among
      38 individuals of 12 co-occurring weed species. Sequence analysis revealed that
      all nine PCR detections from among 106 individuals of five Hemiptera insect
      species from the site, three of which had previously been reported as likely
      vectors, were false positives. This study demonstrates the importance of
      sequencing to complement PCR detection and avoid potentially inaccurate
      conclusions regarding vectors, highlights that sampling over a wide spatio
      temporal scale is important for vector and alternative host studies, and extends
      to eight the number of phytoplasma 16 Sr groups known from lucerne.

PMID- 27886230
TI  - Controlling the Electromagnetic Field Confinement with Metamaterials.
AB  - The definition of a precise illumination region is essential in many applications
      where the electromagnetic field should be confined in some specific volume. By
      using conventional structures, it is difficult to achieve an adequate confinement
      distance (or volume) with negligible levels of radiation leakage beyond it.
      Although metamaterial structures and metasurfaces are well-known to provide high
      controllability of their electromagnetic properties, this feature has not yet
      been applied to solve this problem. We present a method of electromagnetic field
      confinement based on the generation of evanescent waves by means of metamaterial
      structures. With this method, the confinement volume can be controlled, namely,
      it is possible to define a large area with an intense field without radiation
      leakage. A prototype working in the microwave region has been implemented, and
      very good agreement between the measurements and the theoretical prediction of
      field distribution has been obtained.

PMID- 27886228
TI  - Plasticity in the olfactory bulb of the maternal mouse is prevented by
      gestational stress.
AB  - Maternal stress is associated with an altered mother-infant relationship that
      endangers offspring development, leading to emotional/behavioral problems.
      However, little research has investigated the stress-induced alterations of the
      maternal brain that could underlie such a disruption of mother-infant bonding.
      Olfactory cues play an extensive role in the coordination of mother-infant
      interactions, suggesting that motherhood may be associated to enhanced olfactory
      performances, and that this effect may be abolished by maternal stress. To test
      this hypothesis, we analyzed the impact of motherhood under normal conditions or
      after gestational stress on olfactory functions in C57BL/6 J mice. We report that
      gestational stress alters maternal behavior and prevents both mothers' ability to
      discriminate pup odors and motherhood-induced enhancement in odor memory. We
      investigated adult bulbar neurogenesis as a potential mechanism of the enhanced
      olfactory function in mothers and found that motherhood was associated with an
      increased complexity of the dendritic tree of newborn neurons. This motherhood
      evoked remodeling was totally prevented by gestational stress. Altogether, our
      results may thus provide insight into the neural changes that could contribute to
      altered maternal behavior in stressed mothers.

PMID- 27886231
TI  - A universal synthetic route to carbon nanotube/transition metal oxide nano
      composites for lithium ion batteries and electrochemical capacitors.
AB  - We report a simple synthetic approach to coaxially grow transition metal oxide
      (TMO) nanostructures on carbon nanotubes (CNT) with ready control of phase and
      morphology. A thin (~4 nm) sulfonated-polystyrene (SPS) pre-coating is essential
      for the deposition of transition metal based materials. This layer has abundant
      sulfonic groups (-SO3-) that can effectively attract Ni2+, Co2+, Zn2+ ions
      through electrostatic interaction and induce them via hydrolysis, dehydration and
      recrystallization to form coaxial (NiO, Co3O4, NiCoO2 and ZnCo2O4) shells and a
      nanosheet-like morphology around CNT. These structures possess a large active
      surface and enhanced structural robustness when used as electrode materials for
      lithium-ion batteries (LIBs) and electrochemical capacitors (ECs). As electrodes
      for LIBs, the ZnCo2O4@CNT material shows extremely stable cycling performance
      with a discharge capacity of 1068 mAh g-1 after 100 cycles at a current density
      of 400 mAg-1. For EC applications, the NiCoO2@CNT exhibits a high capacitance of
      1360 Fg-1 at current densities of 10 Ag-1 after 3000 cycles and an overall
      capacitance loss of only 1.4%. These results demonstrate the potential of such
      hybrid materials meeting the crucial requirements of cycling stability and high
      rate capability for energy conversion and storage devices.

PMID- 27886232
TI  - Amplification of resonant field enhancement by plasmonic lattice coupling in
      metallic slit arrays.
AB  - Nonlinear spectroscopic investigation in the terahertz (THz) range requires
      significant field strength of the light fields. It is still a challenge to obtain
      the required field strengths in free space from table-top laser systems at
      sufficiently high repetition rates to enable quantitative nonlinear spectroscopy.
      It is well known that local enhancement of the THz field can be obtained for
      instance in narrow apertures in metallic films. Here we show by simulation,
      analytical modelling and experiment that the achievable field enhancement in a
      two-dimensional array of slits with micrometer dimensions in a metallic film can
      be increased by at least 60% compared to the enhancement in an isolated slit. The
      additional enhancement is obtained by optimized plasmonic coupling between the
      lattice modes and the resonance of the individual slits. Our results indicate a
      viable route to sensitive schemes for THz spectroscopy with slit arrays
      manufactured by standard UV photolithography, with local field strengths in the
      multi-ten-MV/cm range at kHz repetition rates, and tens of kV/cm at oscillator
      repetition rates.

PMID- 27886233
TI  - Apparent Power Law Scaling of Variable Range Hopping Conduction in Carbonized
      Polymer Nanofibers.
AB  - We induce dramatic changes in the structure of conducting polymer nanofibers by
      carbonization at 800  degrees C and compare charge transport properties between
      carbonized and pristine nanofibers. Despite the profound structural differences,
      both types of systems display power law dependence of current with voltage and
      temperature, and all measurements can be scaled into a single universal curve. We
      analyze our experimental data in the framework of variable range hopping and
      argue that this mechanism can explain transport properties of pristine polymer
      nanofibers as well.

PMID- 27886234
TI  - Expedited Holonomic Quantum Computation via Net Zero-Energy-Cost Control in
      Decoherence-Free Subspace.
AB  - Holonomic quantum computation (HQC) may not show its full potential in quantum
      speedup due to the prerequisite of a long coherent runtime imposed by the
      adiabatic condition. Here we show that the conventional HQC can be dramatically
      accelerated by using external control fields, of which the effectiveness is
      exclusively determined by the integral of the control fields in the time domain.
      This control scheme can be realized with net zero energy cost and it is fault
      tolerant against fluctuation and noise, significantly relaxing the experimental
      constraints. We demonstrate how to realize the scheme via decoherence-free
      subspaces. In this way we unify quantum robustness merits of this fault-tolerant
      control scheme, the conventional HQC and decoherence-free subspace, and propose
      an expedited holonomic quantum computation protocol.

PMID- 27886235
TI  - Time-lapse 3-D measurements of a glucose biosensor in multicellular spheroids by
      light sheet fluorescence microscopy in commercial 96-well plates.
AB  - Light sheet fluorescence microscopy has previously been demonstrated on a
      commercially available inverted fluorescence microscope frame using the method of
      oblique plane microscopy (OPM). In this paper, OPM is adapted to allow time-lapse
      3-D imaging of 3-D biological cultures in commercially available glass-bottomed
      96-well plates using a stage-scanning OPM approach (ssOPM). Time-lapse 3-D
      imaging of multicellular spheroids expressing a glucose Forster resonance energy
      transfer (FRET) biosensor is demonstrated in 16 fields of view with image
      acquisition at 10 minute intervals. As a proof-of-principle, the ssOPM system is
      also used to acquire a dose response curve with the concentration of glucose in
      the culture medium being varied across 42 wells of a 96-well plate with the whole
      acquisition taking 9 min. The 3-D image data enable the FRET ratio to be measured
      as a function of distance from the surface of the spheroid. Overall, the results
      demonstrate the capability of the OPM system to measure spatio-temporal changes
      in FRET ratio in 3-D in multicellular spheroids over time in a multi-well plate
      format.

PMID- 27886236
TI  - Anatomical recovery of the spinal glutamatergic system following a complete
      spinal cord injury in lampreys.
AB  - Lampreys recover locomotion following a spinal cord injury (SCI). Glutamate is
      necessary to initiate and control locomotion and recent data suggest a crucial
      role for intraspinal neurons in functional recovery following SCI. We aimed to
      determine whether, in lampreys, axotomized spinal glutamatergic neurons, which
      lose glutamate immunoreactivity immediately after SCI, recover it later on and to
      study the long-term evolution and anatomical recovery of the spinal glutamatergic
      system after SCI. We used glutamate immunoreactivity to study changes in the
      glutamatergic system, tract-tracing to label axotomized neurons and TUNEL
      labelling to study cell death. Transections of the cord were made at the level of
      the fifth gill. TUNEL experiments indicated that cell death is a minor
      contributor to the initial loss of glutamate immunoreactivity. At least some of
      the axotomized neurons lose glutamate immunoreactivity, survive and recover
      glutamate immunoreactivity 1 week post-lesion (wpl). We observed a progressive
      increase in the number of glutamatergic neurons/processes until an almost
      complete anatomical recovery at 10 wpl. Among all the glutamatergic populations,
      the population of cerebrospinal fluid-contacting cells is the only one that never
      recovers. Our results indicate that full recovery of the glutamatergic system is
      not necessary for the restoration of function in lampreys.

PMID- 27886237
TI  - LukMF' is the major secreted leukocidin of bovine Staphylococcus aureus and is
      produced in vivo during bovine mastitis.
AB  - Staphylococcus aureus is a major human and animal pathogen and a common cause of
      mastitis in cattle. S. aureus secretes several leukocidins that target bovine
      neutrophils, crucial effector cells in the defence against bacterial pathogens.
      In this study, we investigated the role of staphylococcal leukocidins in the
      pathogenesis of bovine S. aureus disease. We show that LukAB, in contrast to the
      gamma-hemolysins, LukED, and LukMF', was unable to kill bovine neutrophils, and
      identified CXCR2 as a bovine receptor for HlgAB and LukED. Furthermore, we
      assessed functional leukocidin secretion by bovine mastitis isolates and observed
      that, although leukocidin production was strain dependent, LukMF' was most
      abundantly secreted and the major toxin killing bovine neutrophils. To determine
      the role of LukMF' in bovine mastitis, cattle were challenged with high (S1444)
      or intermediate (S1449, S1463) LukMF'-producing isolates. Only animals infected
      with S1444 developed severe clinical symptoms. Importantly, LukM was produced in
      vivo during the course of infection and levels in milk were associated with the
      severity of mastitis. Altogether, these findings underline the importance of
      LukMF' as a virulence factor and support the development of therapeutic
      approaches targeting LukMF' to control S. aureus mastitis in cattle.

PMID- 27886238
TI  - MC5r and A2Ar Deficiencies During Experimental Autoimmune Uveitis Identifies
      Distinct T cell Polarization Programs and a Biphasic Regulatory Response.
AB  - Autoantigen-specific regulatory immunity emerges in the spleen of mice recovering
      from experimental autoimmune uveitis (EAU), a murine model for human autoimmune
      uveoretinitis. This regulatory immunity provides induced tolerance to ocular
      autoantigen, and requires melanocortin 5 receptor (MC5r) expression on antigen
      presenting cells with adenosine 2 A receptor (A2Ar) expression on T cells. During
      EAU it is not well understood what roles MC5r and A2Ar have on promoting
      regulatory immunity. Cytokine profile analysis during EAU revealed MC5r and A2Ar
      each mediate distinct T cell responses, and are responsible for a functional
      regulatory immune response in the spleen. A2Ar stimulation at EAU onset did not
      augment this regulatory response, nor bypass the MC5r requirement to induce
      regulatory immunity. The importance of this pathway in human autoimmune uveitis
      was assayed. PBMC from uveitis patients were assayed for MC5r expression on
      monocytes and A2Ar on T cells, and comparison between uveitis patients and
      healthy controls had no significant difference. The importance for MC5r and A2Ar
      expression in EAU to promote the induction of protective regulatory immunity, and
      the expression of MC5r and A2Ar on human immune cells, suggests that it may be
      possible to utilize the melanocortin-adenosinergic pathways to induce protective
      immunity in uveitic patients.

PMID- 27886239
TI  - Histone deacetylase 1 plays a predominant pro-oncogenic role in EMU-myc driven B
      cell lymphoma.
AB  - The two histone deacetylases (Hdacs), Hdac1 and Hdac2, are erasers of acetylation
      marks on histone tails, and are important regulators of gene expression that were
      shown to play important roles in hematological malignancies. However, several
      recent studies reported opposing tumor-suppressive or tumor-promoting roles for
      Hdac1 and Hdac2. Here, we investigated the functional role of Hdac1 and Hdac2
      using the EMU-myc mouse model of B cell lymphoma. We demonstrate that Hdac1 and
      Hdac2 have a pro-oncogenic role in both EMU-myc tumorigenesis and tumor
      maintenance. Hdac1 and Hdac2 promote tumorigenesis in a gene dose-dependent
      manner, with a predominant function of Hdac1. Our data show that Hdac1 and Hdac2
      impact on EMU-myc B cell proliferation and apoptosis and suggest that a critical
      level of Hdac activity may be required for EMU-myc tumorigenesis and proper B
      cell development. This provides the rationale for utilization of selective Hdac1
      and Hdac2 inhibitors in the treatment of hematological malignancies.

PMID- 27886240
TI  - Identification of ER-000444793, a Cyclophilin D-independent inhibitor of
      mitochondrial permeability transition, using a high-throughput screen in
      cryopreserved mitochondria.
AB  - Growing evidence suggests persistent mitochondrial permeability transition pore
      (mPTP) opening is a key pathophysiological event in cell death underlying a
      variety of diseases. While it has long been clear the mPTP is a druggable target,
      current agents are limited by off-target effects and low therapeutic efficacy.
      Therefore identification and development of novel inhibitors is necessary. To
      rapidly screen large compound libraries for novel mPTP modulators, a method was
      exploited to cryopreserve large batches of functionally active mitochondria from
      cells and tissues. The cryopreserved mitochondria maintained respiratory coupling
      and ATP synthesis, Ca2+ uptake and transmembrane potential. A high-throughput
      screen (HTS), using an assay of Ca2+-induced mitochondrial swelling in the
      cryopreserved mitochondria identified ER-000444793, a potent inhibitor of mPTP
      opening. Further evaluation using assays of Ca2+-induced membrane depolarisation
      and Ca2+ retention capacity also indicated that ER-000444793 acted as an
      inhibitor of the mPTP. ER-000444793 neither affected cyclophilin D (CypD)
      enzymatic activity, nor displaced of CsA from CypD protein, suggesting a
      mechanism independent of CypD inhibition. Here we identified a novel, CypD
      independent inhibitor of the mPTP. The screening approach and compound described
      provides a workflow and additional tool to aid the search for novel mPTP
      modulators and to help understand its molecular nature.

PMID- 27886241
TI  - Habitat generalists and specialists in microbial communities across a terrestrial
      freshwater gradient.
AB  - Observations of distributions of microorganisms and their differences in
      community composition across habitats provide evidence of biogeographical
      patterns. However, little is known about the processes controlling transfers
      across habitat gradients. By analysing the overall microbial community
      composition (bacteria, fungi, archaea) across a terrestrial-freshwater gradient,
      the aim of this study was to understand the spatial distribution patterns of
      populations and identify taxa capable of crossing biome borders. Barcoded 454
      pyrosequencing of taxonomic gene markers was used to describe the microbial
      communities in adjacent soil, freshwater and sediment samples and study the role
      of biotic and spatial factors in shaping their composition. Few habitat
      generalists but a high number of specialists were detected indicating that
      microbial community composition was mainly regulated by species sorting and niche
      partitioning. Biotic interactions within microbial groups based on an association
      network underlined the importance of Actinobacteria, Sordariomycetes,
      Agaricomycetes and Nitrososphaerales in connecting among biomes. Even if
      dispersion seemed limited, the shore of the lake represented a transition area,
      allowing populations to cross the biome boundaries. In finding few broadly
      distributed populations, our study points to biome specialization within
      microbial communities with limited potential for dispersal and colonization of
      new habitats along the terrestrial-freshwater continuum.

PMID- 27886243
TI  - Creating new layered structures at high pressures: SiS2.
AB  - Old and novel layered structures are attracting increasing attention for their
      physical, electronic, and frictional properties. SiS2, isoelectronic to SiO2, CO2
      and CS2, is a material whose phases known experimentally up to 6 GPa exhibit 1D
      chain-like, 2D layered and 3D tetrahedral structures. We present highly
      predictive ab initio calculations combined with evolutionary structure search and
      molecular dynamics simulations of the structural and electronic evolution of SiS2
      up to 100 GPa. A highly stable CdI2-type layered structure, which is octahedrally
      coordinated with space group surprisingly appears between 4 and up to at least
      100 GPa. The tetrahedral-octahedral switch is naturally expected upon
      compression, unlike the layered character realized here by edge-sharing SiS6
      octahedral units connecting within but not among sheets. The predicted phase is
      semiconducting with an indirect band gap of about 2 eV at 10 GPa, decreasing
      under pressure until metallization around 40 GPa. The robustness of the layered
      phase suggests possible recovery at ambient pressure, where calculated phonon
      spectra indicate dynamical stability. Even a single monolayer is found to be
      dynamically stable in isolation, suggesting that it could possibly be sheared or
      exfoliated from bulk -SiS2.

PMID- 27886245
TI  - Early evidence of stone tool use in bone working activities at Qesem Cave,
      Israel.
AB  - For a long while, the controversy surrounding several bone tools coming from pre
      Upper Palaeolithic contexts favoured the view of Homo sapiens as the only species
      of the genus Homo capable of modifying animal bones into specialised tools.
      However, evidence such as South African Early Stone Age modified bones, European
      Lower Palaeolithic flaked bone tools, along with Middle and Late Pleistocene bone
      retouchers, led to a re-evaluation of the conception of Homo sapiens as the
      exclusive manufacturer of specialised bone tools. The evidence presented herein
      include use wear and bone residues identified on two flint scrapers as well as a
      sawing mark on a fallow deer tibia, not associated with butchering activities.
      Dated to more than 300 kya, the evidence here presented is among the earliest
      related to tool-assisted bone working intended for non-dietary purposes, and
      contributes to the debate over the recognition of bone working as a much older
      behaviour than previously thought. The results of this study come from the
      application of a combined methodological approach, comprising use wear analysis,
      residue analysis, and taphonomy. This approach allowed for the retrieval of both
      direct and indirect evidence of tool-assisted bone working, at the Lower
      Palaeolithic site of Qesem Cave (Israel).

PMID- 27886244
TI  - Reconstructing Networks from Profit Sequences in Evolutionary Games via a
      Multiobjective Optimization Approach with Lasso Initialization.
AB  - Evolutionary games (EG) model a common type of interactions in various complex,
      networked, natural and social systems. Given such a system with only profit
      sequences being available, reconstructing the interacting structure of EG
      networks is fundamental to understand and control its collective dynamics.
      Existing approaches used to handle this problem, such as the lasso, a convex
      optimization method, need a user-defined constant to control the tradeoff between
      the natural sparsity of networks and measurement error (the difference between
      observed data and simulated data). However, a shortcoming of these approaches is
      that it is not easy to determine these key parameters which can maximize the
      performance. In contrast to these approaches, we first model the EG network
      reconstruction problem as a multiobjective optimization problem (MOP), and then
      develop a framework which involves multiobjective evolutionary algorithm (MOEA),
      followed by solution selection based on knee regions, termed as MOEANet, to solve
      this MOP. We also design an effective initialization operator based on the lasso
      for MOEA. We apply the proposed method to reconstruct various types of synthetic
      and real-world networks, and the results show that our approach is effective to
      avoid the above parameter selecting problem and can reconstruct EG networks with
      high accuracy.

PMID- 27886242
TI  - Exploring the molecular basis of age-related disease comorbidities using a multi
      omics graphical model.
AB  - Although association studies have unveiled numerous correlations of biochemical
      markers with age and age-related diseases, we still lack an understanding of
      their mutual dependencies. To find molecular pathways that underlie age-related
      diseases as well as their comorbidities, we integrated aging markers from four
      different high-throughput omics datasets, namely epigenomics, transcriptomics,
      glycomics and metabolomics, with a comprehensive set of disease phenotypes from
      510 participants of the TwinsUK cohort. We used graphical random forests to
      assess conditional dependencies between omics markers and phenotypes while
      eliminating mediated associations. Applying this novel approach for multi-omics
      data integration yields a model consisting of seven modules that represent
      distinct aspects of aging. These modules are connected by hubs that potentially
      trigger comorbidities of age-related diseases. As an example, we identified urate
      as one of these key players mediating the comorbidity of renal disease with body
      composition and obesity. Body composition variables are in turn associated with
      inflammatory IgG markers, mediated by the expression of the hormone oxytocin.
      Thus, oxytocin potentially contributes to the development of chronic low-grade
      inflammation, which often accompanies obesity. Our multi-omics graphical model
      demonstrates the interconnectivity of age-related diseases and highlights
      molecular markers of the aging process that might drive disease comorbidities.

PMID- 27886246
TI  - Disorder and dephasing as control knobs for light transport in optical fiber
      cavity networks.
AB  - Transport phenomena represent a very interdisciplinary topic with applications in
      many fields of science, such as physics, chemistry, and biology. In this context,
      the possibility to design a perfectly controllable experimental setup, where to
      tune and optimize its dynamics parameters, is a challenging but very relevant
      task to emulate, for instance, the transmission of energy in light harvesting
      processes. Here, we experimentally build a scalable and controllable transport
      emulator based on optical fiber cavity networks where the system noise parameters
      can be finely tuned while maximizing the transfer efficiency. In particular, we
      demonstrate that disorder and dephasing noise are two control knobs allowing one
      to play with constructive and destructive interference to optimize the transport
      paths towards an exit site. These optical setups, on one side, mimic the
      transport dynamics in natural photosynthetic organisms and, on the other, are
      very promising platforms to artificially design optimal nanoscale structures for
      novel, more efficient, clean energy technologies.

PMID- 27886247
TI  - Acupuncture and Moxibustion have Different Effects on Fatigue by Regulating the
      Autonomic Nervous System: A Pilot Controlled Clinical Trial.
AB  - In order to investigate the different effects of acupuncture and moxibustion on
      chronic fatigue syndrome (CFS) and alterations in the autonomic nervous system by
      measuring heart rate variability (HRV). Forty-five participants were recruited
      and randomly divided into 3 groups using a randomization schedule. The control
      group (CG, n = 15) and the acupuncture group (AG, n = 15) were treated by
      manipulation acupuncture, and the moxibustion group (MG, n = 15) was treated by
      indirect moxibustion. Primary outcomes were the scores of the Fatigue Assessment
      Instrument (FAI). Secondary outcomes were the HRV parameters which can reflect
      activity of the autonomic nervous system. This trial considered both
      instantaneous changes and long-term effectiveness. FAI scores decreased after the
      4th and 10th treatments in the 3 groups. The decrease in FAI in the MG was
      greater than that in the AG. Acupuncture was more effective in instantaneous
      changes of HRV and moxibustion in long-term aspects. Both acupuncture and
      moxibustion improved fatigue in CFS patients, but moxibustion was more effective.
      The possible mechanism of the intervention may be through activation of the vagus
      nerve. Moxibustion was more effective than acupuncture in long-term treatment of
      CFS.

PMID- 27886250
TI  - Shared somatosensory and motor functions in musicians.
AB  - Skilled individuals are characterized by fine-tuned perceptual and motor
      functions. Here, we tested the idea that the sensory and motor functions of
      highly-trained individuals are coupled. We assessed the relationships among
      multifaceted somatosensory and motor functions of expert pianists. The results
      demonstrated a positive covariation between the acuity of weight discrimination
      and the precision of force control during piano keystrokes among the pianists but
      not among the non-musicians. However, neither the age of starting musical
      training nor the total amount of life-long piano practice was correlated with
      these sensory-motor functions in the pianists. Furthermore, a difference between
      the pianists and non-musicians was absent for the weight discrimination acuity
      but present for precise force control during keystrokes. The results suggest that
      individuals with innately superior sensory function had finer motor control only
      in a case of having undergone musical training. Intriguingly, the tactile spatial
      acuity of the fingertip was superior in the pianists compared with the non
      musicians but was not correlated with any functions representing fine motor
      control among the pianists. The findings implicate the presence of two distinct
      mechanisms of sensorimotor learning elicited by musical training, which occur
      either independently in individual sensorimotor modalities or through interacting
      between modalities.

PMID- 27886249
TI  - Impairment of PDGF-induced chemotaxis by extracellular alpha-synuclein through
      selective inhibition of Rac1 activation.
AB  - Parkinson's disease (PD) is characterized by alpha-synuclein (alpha-Syn)-positive
      intracytoplasmic inclusions, known as Lewy bodies. Although it is known that
      extracellular alpha-Syn is detected in the plasma and cerebrospinal fluid, its
      physiological significance remains unclear. Here, we show that extracellular
      alpha-Syn suppresses platelet-derived growth factor (PDGF)-induced chemotaxis in
      human neuroblastoma SH-SY5Y cells. The inhibitory effect was stronger in the
      mutant alpha-Syn(A53T), found in hereditary PD, and the degree of inhibition was
      time-dependent, presumably because of the oligomerization of alpha-Syn. PDGF
      induced activation of Akt or Erk was not influenced by alpha-Syn(A53T). Further
      studies revealed that alpha-Syn(A53T) inhibited PDGF-induced Rac1 activation,
      whereas Cdc42 activation remained unaffected, resulting in unbalanced actin
      filament remodeling. These results shed light on the understanding of
      pathological as well as physiological functions of extracellular alpha-Syn in
      neuronal cells.

PMID- 27886248
TI  - Ultrasensitive, rapid and inexpensive detection of DNA using paper based lateral
      flow assay.
AB  - Sensitive, specific, rapid, inexpensive and easy-to-use nucleic acid tests for
      use at the point-of-need are critical for the emerging field of personalised
      medicine for which companion diagnostics are essential, as well as for
      application in low resource settings. Here we report on the development of a
      point-of-care nucleic acid lateral flow test for the direct detection of
      isothermally amplified DNA. The recombinase polymerase amplification method is
      modified slightly to use tailed primers, resulting in an amplicon with a duplex
      flanked by two single stranded DNA tails. This tailed amplicon facilitates
      detection via hybridisation to a surface immobilised oligonucleotide capture
      probe and a gold nanoparticle labelled reporter probe. A detection limit of 1 *
      10-11 M (190 amol), equivalent to 8.67 * 105 copies of DNA was achieved, with the
      entire assay, both amplification and detection, being completed in less than 15
      minutes at a constant temperature of 37  degrees C. The use of the tailed primers
      obviates the need for hapten labelling and consequent use of capture and reporter
      antibodies, whilst also avoiding the need for any post-amplification processing
      for the generation of single stranded DNA, thus presenting an assay that can
      facilely find application at the point of need.

PMID- 27886251
TI  - Fragmenting networks by targeting collective influencers at a mesoscopic level.
AB  - A practical approach to protecting networks against epidemic processes such as
      spreading of infectious diseases, malware, and harmful viral information is to
      remove some influential nodes beforehand to fragment the network into small
      components. Because determining the optimal order to remove nodes is a
      computationally hard problem, various approximate algorithms have been proposed
      to efficiently fragment networks by sequential node removal. Morone and Makse
      proposed an algorithm employing the non-backtracking matrix of given networks,
      which outperforms various existing algorithms. In fact, many empirical networks
      have community structure, compromising the assumption of local tree-like
      structure on which the original algorithm is based. We develop an immunization
      algorithm by synergistically combining the Morone-Makse algorithm and coarse
      graining of the network in which we regard a community as a supernode. In this
      way, we aim to identify nodes that connect different communities at a reasonable
      computational cost. The proposed algorithm works more efficiently than the Morone
      Makse and other algorithms on networks with community structure.

PMID- 27886252
TI  - Dressed Photons Induced Resistance Oscillation and Zero Resistance in Arrayed
      Simple Harmonic Oscillators with No Impurity.
AB  - We investigate a system of an array of N simple harmonic oscillators (SHO)
      interacting with photons through QED interaction. As the energy of photon is
      around the spacing between SHO energy levels, energy gaps appear in the
      dispersion relation of the interacted (dressed) photons. This is quite different
      from the dispersion relation of free photons. Due to interactions between dressed
      photonic field and arrayed SHO, the photoresistance of this system shows
      oscillations and also drops to zero as irradiated by EM field of varying
      frequencies.

PMID- 27886254
TI  - Two novel mutations in PRPF3 causing autosomal dominant retinitis pigmentosa.
AB  - Retinitis pigmentosa (RP) is a heterogeneous set of hereditary eye diseases,
      characterized by selective death of photoreceptor cells in the retina, resulting
      in progressive visual impairment. Approximately 20-40% of RP cases are autosomal
      dominant RP (ADRP). In this study, a Chinese ADRP family previously localized to
      the region between D1S2819 and D1S2635 was sequenced via whole-exome sequencing
      and a variant c.1345C > G (p.R449G) was identified in PRPF3. The Sanger
      sequencing was performed in probands of additional 95 Chinese ADRP families to
      investigate the contribution of PRPF3 to ADRP in Chinese population and another
      variant c.1532A > C (p.H511P) was detected in one family. These two variants, co
      segregate with RP in two families respectively and both variants are predicted to
      be pathological. This is the first report about the spectrum of PRPF3 mutations
      in Chinese population, leading to the identification of two novel PRPF3
      mutations. Only three clustered mutations in PRPF3 have been identified so far in
      several populations and all are in exon 11. Our study expands the spectrum of
      PRPF3 mutations in RP. We also demonstrate that PRPF3 mutations are responsible
      for 2.08% of ADRP families in this cohort indicating that PRPF3 mutations might
      be relatively rare in Chinese ADRP patients.

PMID- 27886253
TI  - CXCR4/CXCL12 axis counteracts hematopoietic stem cell exhaustion through
      selective protection against oxidative stress.
AB  - Hematopoietic stem cells (HSCs) undergo self-renewal to maintain hematopoietic
      homeostasis for lifetime, which is regulated by the bone marrow (BM)
      microenvironment. The chemokine receptor CXCR4 and its ligand CXCL12 are critical
      factors supporting quiescence and BM retention of HSCs. Here, we report an
      unknown function of CXCR4/CXCL12 axis in the protection of HSCs against oxidative
      stress. Disruption of CXCR4 receptor in mice leads to increased endogenous
      production of reactive oxygen species (ROS), resulting in p38 MAPK activation,
      increased DNA double-strand breaks and apoptosis leading to marked reduction in
      HSC repopulating potential. Increased ROS levels are directly responsible for
      exhaustion of the HSC pool and are not linked to loss of quiescence of CXCR4
      deficient HSCs. Furthermore, we report that CXCL12 has a direct rescue effect on
      oxidative stress-induced HSC damage at the mitochondrial level. These data
      highlight the importance of CXCR4/CXCL12 axis in the regulation of lifespan of
      HSCs by limiting ROS generation and genotoxic stress.

PMID- 27886255
TI  - Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain
      increase the virulence of H7N7 influenza A virus.
AB  - The PA N-terminal domain (PA-Nter) is essential for viral transcription and
      replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A
      in recently emerged avian influenza A viruses (IAVs) with potential effect on
      virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter
      substitutions into avian H7N7 IAV by reverse genetics. Our results showed that
      single substitution V63I and combined substitutions, I61T/V63I and
      A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in
      mammalian cells. Meanwhile, these substitutions conferred higher virus
      transcription/replication capacity by producing more mRNA, cRNA and vRNA.
      Consistently, the polymerase activity and the endonuclease activity were enhanced
      by these PA-Nter substitutions. Notably, substitutions V63I and Mfour strongly
      increased virus replication and virulence in mice. Collectively, our findings
      demonstrated that the PA-Nter substitutions V63I and Mfour enhanced IAV
      pathogenicity through modification of the polymerase activity and the
      endonuclease activity, which added to the evolving knowledge of IAV virulence
      determinants.

PMID- 27886256
TI  - Structural insights into the interaction of the ribosomal P stalk protein P2 with
      a type II ribosome-inactivating protein ricin.
AB  - Ricin is a type II ribosome-inactivating protein (RIP) that depurinates A4324 at
      the sarcin-ricin loop of 28 S ribosomal RNA (rRNA), thus inactivating the
      ribosome by preventing elongation factors from binding to the GTPase activation
      centre. Recent studies have disclosed that the conserved C-terminal domain (CTD)
      of eukaryotic ribosomal P stalk proteins is involved in the process that RIPs
      target ribosome. However, the details of the molecular interaction between ricin
      and P stalk proteins remain unknown. Here, we report the structure of ricin-A
      chain (RTA) in a complex with the CTD of the human ribosomal protein P2. The
      structure shows that the Phe111, Leu113 and Phe114 residues of P2 insert into a
      hydrophobic pocket formed by the Tyr183, Arg235, Phe240 and Ile251 residues of
      RTA, while Asp115 of P2 forms hydrogen bonds with Arg235 of RTA. The key residues
      in RTA and P2 for complex formation were mutated, and their importance was
      determined by pull-down assays. The results from cell-free translation assays
      further confirmed that the interaction with P stalk proteins is essential for the
      inhibition of protein synthesis by RTA. Taken together, our results provide a
      structural basis that will improve our understanding of the process by which
      ricin targets the ribosome, which will benefit the development of effective small
      molecule inhibitors for use as therapeutic agents.

PMID- 27886257
TI  - An evolutionary conserved interaction between the Gcm transcription factor and
      the SF1 nuclear receptor in the female reproductive system.
AB  - NR5A1 is essential for the development and for the function of steroid producing
      glands of the reproductive system. Moreover, its misregulation is associated with
      endometriosis, which is the first cause of infertility in women. Hr39, the
      Drosophila ortholog of NR5A1, is expressed and required in the secretory cells of
      the spermatheca, the female exocrine gland that ensures fertility by secreting
      substances that attract and capacitate the spermatozoids. We here identify a
      direct regulator of Hr39 in the spermatheca: the Gcm transcription factor.
      Furthermore, lack of Gcm prevents the production of the secretory cells and leads
      to female sterility in Drosophila. Hr39 regulation by Gcm seems conserved in
      mammals and involves the modification of the DNA methylation profile of mNr5a1.
      This study identifies a new molecular pathway in female reproductive system
      development and suggests a role for hGCM in the progression of reproductive tract
      diseases in humans.

PMID- 27886259
TI  - Atomic Resolution Interfacial Structure of Lead-free Ferroelectric K0.5Na0.5NbO3
      Thin films Deposited on SrTiO3.
AB  - Oxide interface engineering has attracted considerable attention since the
      discovery of its exotic properties induced by lattice strain, dislocation and
      composition change at the interface. In this paper, the atomic resolution
      structure and composition of the interface between the lead-free piezoelectric
      (K0.5Na0.5)NbO3 (KNN) thin films and single-crystalline SrTiO3 substrate were
      investigated by means of scanning transmission electron microscopy (STEM)
      combining with electron energy loss spectroscopy (EELS). A sharp epitaxial
      interface was observed to be a monolayer composed of Nb and Ti cations with a
      ratio of 3/1. The First-Principles Calculations indicated the interface monolayer
      showed different electronic structure and played the vital role in the asymmetric
      charge distribution of KNN thin films near the interface. We also observed the
      gradual relaxation process for the relatively large lattice strains near the
      KNN/STO interface, which remarks a good structure modulation behavior of KNN thin
      films via strain engineering.

PMID- 27886260
TI  - mTOR regulates neuroprotective effect of immunized CD4+Foxp3+ T cells in optic
      nerve ischemia.
AB  - The therapeutic potential of targeting CD4+Foxp3+ regulatory T cells (Tregs)
      remains controversial under the condition of neuroinflammation. This study aims
      to explore the neuroprotective role of Tregs in optic nerve ischemia (ONI) and
      evaluate the therapeutic strategy of Tregs transfer with a focus on targeting the
      mammalian target of rapamycin (mTOR) pathway. Intraocular pressure was
      transiently increased in adult C57BL/6 mice to induce ONI. Mucosal tolerance of
      myelin basic protein (MBP) markedly increased retinal ganglion cell (RGC)
      survival after ONI through enhanced Tregs suppression. mTOR inhibition
      significantly promoted the frequency of MBP-immunized Tregs in vitro with
      increased production of anti-inflammatory cytokines. Transient rapamycin
      treatment highly promoted the immunosuppressive capacity of Tregs and inhibited
      retinal inflammation in ONI animals. Intravenous infusion of MBP-immunized Tregs,
      instead of regular Tregs, beneficially modulated immune activities of host
      retinal CD11b+ cells and CD4+ effector T cells, leading to significant
      improvement of RGC survival. Importantly, rapamycin treatment further enhanced
      the neuroprotective effect of Tregs transfer. Taken together, these findings
      reveal a fine regulation of mTOR signaling on immunized Tregs after acute retinal
      injury. Adoptive transfer with targeting-mTOR strategy markedly improves neuronal
      recovery after ONI, supporting the therapeutic potentials of Tregs in acute and
      chronic neurological disorder.

PMID- 27886261
TI  - Neil3 induced neurogenesis protects against prion disease during the clinical
      phase.
AB  - Base excision repair (BER) is the major pathway for repair of oxidative DNA
      damage. Mice with genetic knockout of the BER enzyme Neil3 display compromised
      neurogenesis in the sub-ventricular zone of the lateral ventricle and sub
      granular layer of the dentate gyrus of the hippocampus. To elucidate the impact
      of oxidative DNA damage-induced neurogenesis on prion disease we applied the
      experimental prion disease model on Neil3-deficient mice. The incubation period
      for the disease was similar in both wild type and Neil3-/- mice and the overall
      neuropathology appeared unaffected by Neil3 function. However, disease in the
      Neil3-/- mice was of shorter clinical duration. We observed a mildly reduced
      astrogliosis in the hippocampus and striatum in the Neil3-deficient mice. Brain
      expression levels of neuronal progenitor markers, nestin (Nestin), sex
      determining region Box 2 (Sox2), Class III beta-tubulin (Tuj1) decreased towards
      end-stage prion disease whereas doublecortin (Dcx) levels were less affected.
      Neuronal nuclei (NeuN), a marker for mature neurons declined during prion disease
      and more pronounced in the Neil3-/- group. Microglial activation was prominent
      and appeared unaffected by loss of Neil3. Our data suggest that neurogenesis
      induced by Neil3 repair of oxidative DNA damage protects against prion disease
      during the clinical phase.

PMID- 27886258
TI  - A holistic approach to dissecting SPARC family protein complexity reveals FSTL-1
      as an inhibitor of pancreatic cancer cell growth.
AB  - SPARC is a matricellular protein that is involved in both pancreatic cancer and
      diabetes. It belongs to a wider family of proteins that share structural and
      functional similarities. Relatively little is known about this extended family,
      but evidence of regulatory interactions suggests the importance of a holistic
      approach to their study. We show that Hevin, SPOCKs, and SMOCs are strongly
      expressed within islets, ducts, and blood vessels, suggesting important roles for
      these proteins in the normal pancreas, while FSTL-1 expression is localised to
      the stromal compartment reminiscent of SPARC. In direct contrast to SPARC,
      however, FSTL-1 expression is reduced in pancreatic cancer. Consistent with this,
      FSTL-1 inhibited pancreatic cancer cell proliferation. The complexity of SPARC
      family proteins is further revealed by the detection of multiple cell-type
      specific isoforms that arise due to a combination of post-translational
      modification and alternative splicing. Identification of splice variants lacking
      a signal peptide suggests the existence of novel intracellular isoforms. This
      study underlines the importance of addressing the complexity of the SPARC family
      and provides a new framework to explain their controversial and contradictory
      effects. We also demonstrate for the first time that FSTL-1 suppresses pancreatic
      cancer cell growth.

PMID- 27886262
TI  - Coastal leatherback turtles reveal conservation hotspot.
AB  - Previous studies have shown that the world's largest reptile - the leatherback
      turtle Dermochelys coriacea - conducts flexible foraging migrations that can
      cover thousands of kilometres between nesting sites and distant foraging areas.
      The vast distances that may be travelled by migrating leatherback turtles have
      greatly complicated conservation efforts for this species worldwide. However, we
      demonstrate, using a combination of satellite telemetry and stable isotope
      analysis, that approximately half of the nesting leatherbacks from an important
      rookery in South Africa do not migrate to distant foraging areas, but rather,
      forage in the coastal waters of the nearby Mozambique Channel. Moreover, this
      coastal cohort appears to remain resident year-round in shallow waters (<50 m
      depth) in a relatively fixed area. Stable isotope analyses further indicate that
      the Mozambique Channel also hosts large numbers of loggerhead turtles Caretta
      caretta. The rare presence of a resident coastal aggregation of leatherback
      turtles not only presents a unique opportunity for conservation, but alongside
      the presence of loggerhead turtles and other endangered marine megafauna in the
      Mozambique Channel, highlights the importance of this area as a marine
      biodiversity hotspot.

PMID- 27886263
TI  - Nicotinic and opioid receptor regulation of striatal dopamine D2-receptor
      mediated transmission.
AB  - In addition to dopamine neuron firing, cholinergic interneurons (ChIs) regulate
      dopamine release in the striatum via presynaptic nicotinic receptors (nAChRs) on
      dopamine axon terminals. Synchronous activity of ChIs is necessary to evoke
      dopamine release through this pathway. The frequency-dependence of disynaptic
      nicotinic modulation has led to the hypothesis that nAChRs act as a high-pass
      filter in the dopaminergic microcircuit. Here, we used optogenetics to
      selectively stimulate either ChIs or dopamine terminals directly in the striatum.
      To measure the functional consequence of dopamine release, D2-receptor synaptic
      activity was assessed via virally overexpressed potassium channels (GIRK2) in
      medium spiny neurons (MSNs). We found that nicotinic-mediated dopamine release
      was blunted at higher frequencies because nAChRs exhibit prolonged
      desensitization after a single pulse of synchronous ChI activity. However, when
      dopamine neurons alone were stimulated, nAChRs had no effect at any frequency. We
      further assessed how opioid receptors modulate these two mechanisms of release.
      Bath application of the kappa opioid receptor agonist U69593 decreased D2
      receptor activation through both pathways, whereas the MU opioid receptor agonist
      DAMGO decreased D2-receptor activity only as a result of cholinergic-mediated
      dopamine release. Thus the release of dopamine can be independently modulated
      when driven by either dopamine neurons or cholinergic interneurons.

PMID- 27886265
TI  - Effect of a weak transverse magnetic field on the microstructure in directionally
      solidified peritectic alloys.
AB  - Effect of a weak transverse magnetic field on the microstructures in
      directionally solidified Fe-Ni and Pb-Bi peritectic alloys has been investigated
      experimentally. The results indicate that the magnetic field can induce the
      formation of banded and island-like structures and refine the primary phase in
      peritectic alloys. The above results are enhanced with increasing magnetic field.
      Furthermore, electron probe micro analyzer (EPMA) analysis reveals that the
      magnetic field increases the Ni solute content on one side and enhances the solid
      solubility in the primary phase in the Fe-Ni alloy. The thermoelectric (TE) power
      difference at the liquid/solid interface of the Pb-Bi peritectic alloy is
      measured in situ, and the results show that a TE power difference exists at the
      liquid/solid interface. 3 D numerical simulations for the TE magnetic convection
      in the liquid are performed, and the results show that a unidirectional TE
      magnetic convection forms in the liquid near the liquid/solid interface during
      directional solidification under a transverse magnetic field and that the
      amplitude of the TE magnetic convection at different scales is different. The TE
      magnetic convections on the macroscopic interface and the cell/dendrite scales
      are responsible for the modification of microstructures during directional
      solidification under a magnetic field.

PMID- 27886266
TI  - Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep
      Threshold-Switching Dynamics of AgInSbTe Devices.
AB  - Although phase-change memory (PCM) offers promising features for a 'universal
      memory' owing to high-speed and non-volatility, achieving fast electrical
      switching remains a key challenge. In this work, a correlation between the rate
      of applied voltage and the dynamics of threshold-switching is investigated at
      picosecond-timescale. A distinct characteristic feature of enabling a rapid
      threshold-switching at a critical voltage known as the threshold voltage as
      validated by an instantaneous response of steep current rise from an amorphous
      off to on state is achieved within 250 picoseconds and this is followed by a
      slower current rise leading to crystallization. Also, we demonstrate that the
      extraordinary nature of threshold-switching dynamics in AgInSbTe cells is
      independent to the rate of applied voltage unlike other chalcogenide-based phase
      change materials exhibiting the voltage dependent transient switching
      characteristics. Furthermore, numerical solutions of time-dependent conduction
      process validate the experimental results, which reveal the electronic nature of
      threshold-switching. These findings of steep threshold-switching of 'sub-50 ps
      delay time', opens up a new way for achieving high-speed non-volatile memory for
      mainstream computing.

PMID- 27886264
TI  - Sigma-1 Receptor Agonism Promotes Mechanical Allodynia After Priming the
      Nociceptive System with Capsaicin.
AB  - Sigma-1 receptor antagonists promote antinociception in several models of pain,
      but the effects of sigma-1 agonists on nociception (particularly when the
      nociceptive system is primed) are not so well characterized; therefore we
      evaluated the effects of sigma-1 agonists on pain under different experimental
      conditions. The systemic administration of the selective sigma-1 agonists (+)
      pentazocine and PRE-084, as well as the nonselective sigma-1 agonist
      carbetapentane (used clinically as an antitussive drug), did not alter
      sensitivity to mechanical stimulation under baseline conditions. However, they
      greatly promoted secondary mechanical allodynia after priming the nociceptive
      system with capsaicin. These effects of sigma-1 agonists were consistent in terms
      potency with the affinities of these drugs for sigma-1 receptors, were reversed
      by sigma-1 antagonists, and were not observed in sigma-1 knockout mice,
      indicating that they are sigma-1-mediated. Repeated systemic treatment with PRE
      084 induced proallodynic effects even 24 h after treatment completion, but only
      after the nociceptive system was primed. However, neither the presence of this
      drug in the organism nor changes in sigma-1 receptor expression in areas involved
      in pain processing explains its long-term effects, suggesting that sustained
      sigma-1 agonism induces plastic changes in the nociceptive system that promote
      nociception.

PMID- 27886267
TI  - In vivo characterization of hair and skin derived carbon quantum dots with high
      quantum yield as long-term bioprobes in zebrafish.
AB  - Carbon quantum dots (CDs) were widely investigated because of their tunable
      fluorescence properties and low toxicity. However, so far there have been no
      reports on in vivo functional studies of hair and skin derived CDs. Here, hair
      derived CDs (HCDs) and skin derived CDs (SCDs) were produced by using human hair
      and pig skin as precursors. The quantum yields (QYs) of HCDs and SCDs were quite
      high, compared to citric acid derived CDs (CCDs). HCDs and SCDs possess optimal
      photostability, hypotoxicity and biocompatibility in zebrafish, indicating that
      HCDs and SCDs possess the capacity of being used as fluorescence probes for in
      vivo biological imaging. The long-time observation for fluorescence alternation
      of CDs in zebrafish and the quenching assay of CDs by ATP, NADH and Fe3+ ions
      demonstrated that the decaying process of CDs in vivo might be induced by the
      synergistic effect of the metabolism process. All results indicated that large
      batches and high QYs of CDs can be acquired by employing natural and nontoxic
      hair and skin as precursors. To our knowledge, this is the first time to report
      SCDs, in vivo comparative studies of HCDs, SCDs and CCDs as bioprobes, and
      explore their mechanism of photostability in zebrafish.

PMID- 27886268
TI  - Correlation between superconductivity and bond angle of CrAs chain in non
      centrosymmetric compounds A2Cr3As3 (A = K, Rb).
AB  - Non-centrosymmetric superconductors, whose crystal structure is absent of
      inversion symmetry, have recently received special attentions due to the
      expectation of unconventional pairings and exotic physics associated with such
      pairings. The newly discovered superconductors A2Cr3As3 (A = K, Rb), featured by
      the quasi-one dimensional structure with conducting CrAs chains, belongs to such
      kind of superconductor. In this study, we are the first to report the finding
      that superconductivity of A2Cr3As3 (A = K, Rb) has a positive correlation with
      the extent of non-centrosymmetry. Our in-situ high pressure ac susceptibility and
      synchrotron x-ray diffraction measurements reveal that the larger bond angle of
      As-Cr-As (defined as alpha) in the CrAs chains can be taken as a key factor
      controlling superconductivity. While the smaller bond angle (defined as beta) and
      the distance between the CrAs chains also affect the superconductivity due to
      their structural connections with the alpha angle. We find that the larger value
      of alpha-beta, which is associated with the extent of the non-centrosymmetry of
      the lattice structure, is in favor of superconductivity. These results are
      expected to shed a new light on the underlying mechanism of the superconductivity
      in these Q1D superconductors and also to provide new perspective in understanding
      other non-centrosymmetric superconductors.

PMID- 27886270
TI  - AM fungi patchiness and the clonal growth of Glechoma hederacea in heterogeneous
      environments.
AB  - The effect of AM fungi spatial distribution on individual plant development may
      determine the dynamics of the whole plant community. We investigated whether
      clonal plants display, like for other resources, a foraging or a specialization
      response, to adapt to the distribution of AM fungi. Two separate experiments were
      done to investigate the response of Glechoma hederacea to a heterogeneous
      distribution of a mixture of 3 AM fungi species, and the effects of each species
      on colonization and allocation traits. No specialization and a limited foraging
      response to the heterogeneous distribution of AM fungi was observed. An effect of
      the AM fungal species on plant mass allocation and ramet production, but not on
      spacer length, was detected. Two possible explanations are proposed: (i) the
      plant's responses are buffered by differences in individual effects of the fungal
      species or their root colonization intensity. (ii) the initial heterogeneous
      distribution of AM fungi is perceived as homogeneous by the plant either by
      reduced physiological integration or due to the transfer of AM fungi propagules
      through the stolons. Microscopic and DNA sequencing analyses provided evidence of
      this transfer, thus demonstrating the role of stolons as dispersal vectors of AM
      fungi within the plant clonal network.

PMID- 27886271
TI  - Speciation and genetic diversity in Centaurea subsect. Phalolepis in Anatolia.
AB  - Mountains of Anatolia are one of the main Mediterranean biodiversity hotspots and
      their richness in endemic species amounts for 30% of the flora. Two main factors
      may account for this high diversity: the complex orography and its role as
      refugia during past glaciations. We have investigated seven narrow endemics of
      Centaurea subsection Phalolepis from Anatolia by means of microsatellites and
      ecological niche modelling (ENM), in order to analyse genetic polymorphisms and
      getting insights into their speciation. Despite being narrow endemics, all the
      studied species show moderate to high SSR genetic diversity. Populations are
      genetically isolated, but exchange of genes probably occurred at glacial maxima
      (likely through the Anatolian mountain arches as suggested by the ENM). The lack
      of correlation between genetic clusters and (morpho) species is interpreted as a
      result of allopatric diversification on the basis of a shared gene pool. As
      suggested in a former study in Greece, post-glacial isolation in mountains would
      be the main driver of diversification in these plants; mountains of Anatolia
      would have acted as plant refugia, allowing the maintenance of high genetic
      diversity. Ancient gene flow between taxa that became sympatric during
      glaciations may also have contributed to the high levels of genetic diversity.

PMID- 27886273
TI  - Improving landscape inference by integrating heterogeneous data in the inverse
      Ising problem.
AB  - The inverse Ising problem and its generalizations to Potts and continuous spin
      models have recently attracted much attention thanks to their successful
      applications in the statistical modeling of biological data. In the standard
      setting, the parameters of an Ising model (couplings and fields) are inferred
      using a sample of equilibrium configurations drawn from the Boltzmann
      distribution. However, in the context of biological applications, quantitative
      information for a limited number of microscopic spins configurations has recently
      become available. In this paper, we extend the usual setting of the inverse Ising
      model by developing an integrative approach combining the equilibrium sample with
      (possibly noisy) measurements of the energy performed for a number of arbitrary
      configurations. Using simulated data, we show that our integrative approach
      outperforms standard inference based only on the equilibrium sample or the energy
      measurements, including error correction of noisy energy measurements. As a
      biological proof-of-concept application, we show that mutational fitness
      landscapes in proteins can be better described when combining evolutionary
      sequence data with complementary structural information about mutant sequences.

PMID- 27886269
TI  - In silico clustering of Salmonella global gene expression data reveals novel
      genes co-regulated with the SPI-1 virulence genes through HilD.
AB  - A wide variety of Salmonella enterica serovars cause intestinal and systemic
      infections to humans and animals. Salmonella Patogenicity Island 1 (SPI-1) is a
      chromosomal region containing 39 genes that have crucial virulence roles. The
      AraC-like transcriptional regulator HilD, encoded in SPI-1, positively controls
      the expression of the SPI-1 genes, as well as of several other virulence genes
      located outside SPI-1. In this study, we applied a clustering method to the
      global gene expression data of S. enterica serovar Typhimurium from the COLOMBOS
      database; thus genes that show an expression pattern similar to that of SPI-1
      genes were selected. This analysis revealed nine novel genes that are co
      expressed with SPI-1, which are located in different chromosomal regions.
      Expression analyses and protein-DNA interaction assays showed regulation by HilD
      for six of these genes: gtgE, phoH, sinR, SL1263 (lpxR) and SL4247 were regulated
      directly, whereas SL1896 was regulated indirectly. Interestingly, phoH is an
      ancestral gene conserved in most of bacteria, whereas the other genes show
      characteristics of genes acquired by Salmonella. A role in virulence has been
      previously demonstrated for gtgE, lpxR and sinR. Our results further expand the
      regulon of HilD and thus identify novel possible Salmonella virulence genes.

PMID- 27886272
TI  - Can long-term dentine bonding created in real life be forecasted by parameters
      established in the laboratory?
AB  - Tooth-coloured plastic dental fillings secured by adhesives to tooth structures
      are widely used to fix decayed teeth. Whereas laboratory tests demonstrate rapid
      deterioration of the ability of the adhesives to stick to dentine, clinical
      studies show that these fillings are relatively durable. This discrepancy
      suggests that the parameters used for simulating bond degradation in the
      laboratory setting do not correlate well with clinical outcomes. The present
      study examined the long-term tensile bond strength of resin composite fillings
      performed in real life and under different laboratory-simulated bonding
      conditions to identify parameters that may be used to forecast the durability of
      adhesive bonds created in dentine. Fillings placed in vivo were subjected to
      different periods of intraoral function. In vitro specimens were bonded based on
      whether simulated pulpal pressure (SPP) or thermomechanical cycling was
      implemented, and how long the completed fillings were stored in water.
      Thermomechanical cycling used in combination with long-term water ageing are
      useful in forecasting the decline in strength of resin-dentine bonds created in
      vivo. These parameters should be adopted for future evaluations. Conversely, the
      use of SPP does not appear to be a significant parameter in the simulation of
      long-term clinical deterioration of bond integrity.

PMID- 27886274
TI  - Boosting photoresponse in silicon metal-semiconductor-metal photodetector using
      semiconducting quantum dots.
AB  - Silicon based metal-semiconductor-metal (MSM) photodetectors have faster
      photogeneration and carrier collection across the metal-semiconductor Schottky
      contacts, and CMOS integratibility compared to conventional p-n junction
      photodetectors. However, its operations are limited by low photogeneration,
      inefficient carrier-separation, and low mobility. Here, we show a simple and
      highly effective approach for boosting Si MSM photodetector efficiency by
      uniformly decorating semiconducting CdSe quantum dots on Si channel (Si-QD).
      Significantly higher photocurrent on/off ratio was achieved up to over 500
      compared to conventional Si MSM photodetector (on/off ratio ~5) by increasing
      photogeneration and improving carrier separation. Furthermore, a substrate
      biasing technique invoked wide range of tunable photocurrent on/off ratio in Si
      QD photodetector (ranging from 2.7 to 562) by applying suitable combinations of
      source-drain and substrate biasing conditions. Strong photogeneration and carrier
      separation were achieved by employing Stark effect into the Si-QD hybrid system.
      These results highlight a promising method for enhancing Si MSM photodetector
      efficiency more than 100 times and simultaneously compatible with current silicon
      technologies.

PMID- 27886275
TI  - Conspecific Leaf Litter-Mediated Effect of Conspecific Adult Neighborhood on
      Early-Stage Seedling Survival in A Subtropical Forest.
AB  - Conspecific adults have strong negative effect on the survival of nearby early
      stage seedlings and thus can promote species coexistence by providing space for
      the regeneration of heterospecifics. The leaf litter fall from the conspecific
      adults, and it could mediate this conspecific negative adult effect. However,
      field evidence for such effect of conspecific leaf litter remains absent. In this
      study, we used generalized linear mixed models to assess the effects of
      conspecific leaf litter on the early-stage seedling survival of four dominant
      species (Machilus leptophylla, Litsea elongate, Acer pubinerve and Distylium
      myricoides) in early-stage seedlings in a subtropical evergreen broad-leaved
      forest in eastern China. Our results consistently showed that the conspecific
      leaf litter of three species negatively affected the seedling survival.
      Meanwhile, the traditional conspecific adult neighborhood indices failed to
      detect this negative conspecific adult effect. Our study revealed that the
      accumulation of conspecific leaf litter around adults can largely reduce the
      survival rate of nearby seedlings. Ignoring it could result in underestimation of
      the importance of negative density dependence and negative species interactions
      in the natural forest communities.

PMID- 27886276
TI  - Estradiol-Estrogen Receptor alpha Mediates the Expression of the CXXC5 Gene
      through the Estrogen Response Element-Dependent Signaling Pathway.
AB  - 17beta-estradiol (E2), the primary circulating estrogen hormone, mediates
      physiological and pathophysiological functions of breast tissue mainly through
      estrogen receptor alpha (ERalpha). Upon binding to E2, ERalpha modulates the
      expression of target genes involved in the regulation of cellular proliferation
      primarily through interactions with specific DNA sequences, estrogen response
      elements (EREs). Our previous microarray results suggested that E2-ERalpha
      modulates CXXC5 expression. Because of the presence of a zinc-finger CXXC domain
      (ZF-CXXC), CXXC5 is considered to be a member of the ZF-CXXC family, which binds
      to non-methylated CpG dinucleotides. Although studies are limited, CXXC5 appears
      to participate as a transcription factor, co-regulator and/or epigenetic factor
      in the regulation of cellular events induced by various signaling pathways.
      However, how signaling pathways mediate the expression of CXXC5 is yet unclear.
      Due to the importance of E2-ERalpha signaling in breast tissue, changes in the
      CXXC5 transcription/synthesis could participate in E2-mediated cellular events as
      well. To address these issues, we initially examined the mechanism whereby E2
      ERalpha regulates CXXC5 expression. We show here that CXXC5 is an E2-ERalpha
      responsive gene regulated by the interaction of E2-ERalpha with an ERE present at
      a region upstream of the initial translation codon of the gene.

PMID- 27886277
TI  - A Retrospective Analysis on Two-week Short-course Pre-operative Radiotherapy in
      Elderly Patients with Resectable Locally Advanced Rectal Cancer.
AB  - To validate that a two-week short-course pre-operative radiotherapy regimen is
      feasible, safe, and effective for the management of elderly patients with locally
      advanced rectal cancer (LARC), we retrospectively analyzed 99 radiotherapy-naive
      patients >=70 years of age with LARC. Patients received pelvic radiation therapy
      (3D-CRT 30Gy/10f/2w) followed by TME surgery; some patients received adjuvant
      chemotherapy. The primary endpoint was OS, while the secondary endpoints were
      DFS, safety and response rate. The median follow-up time was 5.1 years. The 5
      year OS and DFS rates were 58.3% and 51.2%, respectively. The completion rate of
      radiotherapy (RT) was 99.0% (98 of 99). Grade 3 acute adverse events, which
      resulted from RT, occurred in only 1 patient (1.0%). In addition, no grade 4
      acute adverse events induced by RT were observed. All 99 patients (100%) were
      able to undergo R0 surgical resection, and 68.6% of the patients received
      sphincter-sparing surgery. The rate of occurrence of clinically relevant post
      operative complications was 12.1%. Three patients (3.0%) achieved pathologic
      complete responses, and forty-three patients (43.4%) achieved pathologic partial
      responses. The rates of T-downsizing and N-downstaging were 30.3% and 55.7%,
      respectively. Therefore, we believe that a two-week short-course pre-operative
      radiotherapy is feasible in elderly patients with resectable LARC.

PMID- 27886278
TI  - A GdAlO3 Perovskite Oxide Electrolyte-Based NOx Solid-State Sensor.
AB  - NOx is a notorious emission from motor vehicles and chemical factories as the
      precursor of acid rain and photochemical smog. Although zirconia-based NOx
      sensors have been developed and showed high sensitivity and selectivity at a high
      temperature of above 800  degrees C, they fail to show good performance, and even
      don't work at the typical work temperature window of the automotive engine (<500 
      degrees C). It still is a formidable challenge for development of mild
      temperature NOx detector or sensor. Herein, a novel amperometric solid-state NOx
      sensor was developed using perovskite-type oxide Gd1-xCaxAlO3-delta(GCA) as the
      electrolyte and NiO as the sensing electrode. NOx sensing properties of the
      device were investigated at the temperature region of 400-500  degrees C. The
      response current value at -300 mV was almost linearly proportional to the NOx
      concentration between 300 and 500 ppm at 500  degrees C. At such a temperature,
      the optimal sensor gave the highest NO2 sensitivity of 20.15 nA/ppm, and the
      maximum response current value reached 5.57 MUA. Furthermore, a 90% response and
      90% recover time to 500 ppm NO2 were about 119 and 92 s, respectively. The
      excellent selectivity and stability towards NOx sensing showed the potential
      application of the sensor in motor vehicles.

PMID- 27886279
TI  - Slowing down light using a dendritic cell cluster metasurface waveguide.
AB  - Slowing down or even stopping light is the first task to realising optical
      information transmission and storage. Theoretical studies have revealed that
      metamaterials can slow down or even stop light; however, the difficulty of
      preparing metamaterials that operate in visible light hinders progress in the
      research of slowing or stopping light. Metasurfaces provide a new opportunity to
      make progress in such research. In this paper, we propose a dendritic cell
      cluster metasurface consisting of dendritic structures. The simulation results
      show that dendritic structure can realise abnormal reflection and refraction
      effects. Single- and double-layer dendritic metasurfaces that respond in visible
      light were prepared by electrochemical deposition. Abnormal Goos-Hanchen (GH)
      shifts were experimentally obtained. The rainbow trapping effect was observed in
      a waveguide constructed using the dendritic metasurface sample. The incident
      white light was separated into seven colours ranging from blue to red light. The
      measured transmission energy in the waveguide showed that the energy escaping
      from the waveguide was zero at the resonant frequency of the sample under a
      certain amount of incident light. The proposed metasurface has a simple
      preparation process, functions in visible light, and can be readily extended to
      the infrared band and communication wavelengths.

PMID- 27886280
TI  - Starvation- and antibiotics-induced formation of persister cells in Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Planktonic stationary and exponential cultures of Pseudomonas
      aeruginosa are highly resistant to killing by bactericidal antimicrobials because
      of the presence of persisters, cells that are multidrug tolerant and play a key
      role in the recalcitrance of biofilm infections. AIM: The aim of this study was
      to investigate the formation of persister cells in P. aeruginosa stationary vs.
      exponential cultures using different class antimicrobials. METHODS: The
      susceptibilities of P. aeruginosa PAO1 wild-type and mutant strains to
      antimicrobials were determined by standard microtiter broth dilution method. In
      order to determine persister formation, dose- and time-dependent killing
      experiments were performed with antibiotics. RESULTS: Ceftazidime (Cephalosporin)
      showed little efficacy against either culture. Stationary-phase cells were more
      tolerant to imipenem (Carbapenem) than exponential cells, leaving a small
      fraction of persisters at high imipenem concentration in both populations.
      Polymyxin B (Polymyxin) appeared to be ineffective at low concentrations against
      both cell populations. Very high polymyxin B concentration completely eradicated
      exponential cells and regrowth was seen in a stationary population. Stationary
      cells were more tolerant to tobramycin (Aminoglycoside) than exponential cells
      but a higher concentration of tobramycin completely eliminated survivors.
      Ciprofloxacin (Fluoroquinolone) at a low concentration resulted in killing of
      both cultures of P. aeruginosa, producing persisters that were invulnerable to
      killing. CONCLUSIONS: Stationary cells appear to be somewhat more tolerant than
      exponential cells in all of these assays. We also showed that nutrient
      deprivation (serine starvation) regulated by stringent and general stress
      response, contribute to the increased tolerance of P. aeruginosa exponential and
      stationary planktonic cells via production of persisters.

PMID- 27886281
TI  - Green and highly efficient synthesis of perylene and naphthalene bisimides in
      nothing but water.
AB  - High-purity, symmetrically substituted perylene and naphthalene bisimides were
      obtained by hydrothermal condensation of monoamines with the corresponding
      bisanhydride. The hydrothermal imidization proceeds quantitatively, without the
      need for organic solvents, catalysts or excess of the amines.

PMID- 27886282
TI  - Dynamics and yields for CHBrCl2 photodissociation from 215-265 nm.
AB  - We investigate the A-band photodissociation of CHBrCl2 at 215, 225, 235, 245,
      255, and 265 nm. Following C-Br bond cleavage, resonance enhanced multiphoton
      ionization and time of flight mass spectrometry provide selective detection of
      the two product channels, from which we quantify the relative quantum yield of
      Br/Br* production. Velocity-map imaging of the photofragments allows us to
      determine the energy partitioning as a function of the photolysis energy for
      different exit channels. The anisotropy present in the imaging data suggests that
      absorption to the 3Q0+(A') state is important throughout the entire region we
      study, though competition with other excited states is evident. The 3Q0+(A')
      state forms an avoided crossing with the 1Q1(A') state, and we find that the
      propensity for adiabatic passage through this crossing region dictates the Br
      yield at longer wavelengths. At shorter wavelengths, Br production from excited
      states not subject to the crossing is more evident. While we find that spin-orbit
      excitation comes largely at the expense of the CHCl2 internal energy, both
      channels still produce highly excited CHCl2 photofragments. Impulsive modeling
      and comparison with similar halomethane dissociations suggests that a high degree
      of rotational excitation is present, dictated by the torque inherent in Cs
      symmetry dissociation and the angular dependence of the potential.

PMID- 27886283
TI  - Gold nanoparticles on OMS-2 for heterogeneously catalyzed aerobic oxidative
      alpha,beta-dehydrogenation of beta-heteroatom-substituted ketones.
AB  - In the presence of Au nanoparticles supported on manganese oxide OMS-2 (Au/OMS
      2), various kinds of beta-heteroatom-substituted alpha,beta-unsaturated ketones
      (heteroatom = N, O, S) can be synthesized through alpha,beta-dehydrogenation of
      the corresponding saturated ketones using O2 (in air) as the oxidant. The
      catalysis of Au/OMS-2 is truly heterogeneous, and the catalyst can be reused.

PMID- 27886284
TI  - Organic functionalization of epitaxial graphene on SiC through direct binding of
      transient radicals from the reaction mixture.
AB  - A common and versatile chemical approach for organic functionalization of
      graphene using a well known reaction mixture has been developed. Here we report
      the chemical binding of substituted aryl or alkyl radicals, transiently generated
      during the preparation of Grignard reagents, onto a graphene sample preloaded in
      a reaction vessel.

PMID- 27886285
TI  - High MOF loading in mixed-matrix membranes utilizing styrene/butadiene
      copolymers.
AB  - A series of styrene/butadiene polymers were combined with up to 90 wt% UiO-66 to
      form mixed-matrix membranes with varying physical properties. Notably,
      polystyrene-block-polybutadiene (SBS) membranes retained much of the
      processability and flexibility of the native polymer component and the porosity,
      chemical tunability, and adsorption of the native MOF.

PMID- 27886286
TI  - Neutral red as a specific light-up fluorescent probe for i-motif DNA.
AB  - We report a specific light-up fluorescent probe for i-motif DNA for the first
      time. Compared with the previously reported probes, neutral red could selectively
      interact with an i-motif and show a significant increase in its fluorescence.
      This feature makes it advantageous for designing label-free fluorescent sensing
      systems.

PMID- 27886287
TI  - A carborane-incorporated mononuclear Co(ii) complex showing zero-field slow
      magnetic relaxation.
AB  - An air-stable mononuclear Co(ii) complex bearing an o-carborane dithiolate ligand
      has been synthesized which shows slow relaxation of magnetization in the absence
      of an applied field and a hysteresis loop at 1.8 K. This is the first example of
      a carborane-incorporated complex that displays SMM properties.

PMID- 27886288
TI  - Exploring the mechanochemical cycle of dynein motor proteins: structural evidence
      of crucial intermediates.
AB  - Dyneins, a class of motor proteins consisting of six AAA+ modules (AAA1-AAA6),
      convert chemical energy derived from the hydrolysis of ATP into mechanical energy
      to walk along the microtubule track towards its minus end while accomplishing
      various cellular tasks including the transportation of various intracellular
      cargos. In a full mechanochemical cycle, dynein goes through ATP binding induced
      open to closed state transition of AAA1, hydrolysis of that ATP and closed to
      open state transition induced by the release of hydrolysed products along with
      linker remodelling in different nucleotide states. Here we built structure based
      models (SBMs) to explore the sequence of events of this mechanochemical cycle
      from structural aspects. Free energy and kinetic simulation approaches on a multi
      basin SBM of dynein reveal the following pathways: (1) in the closing pathway,
      the AAA1 domain first converts to a closed state followed by the movement of the
      linker and (2) in the opening transition, initially the AAA1 domain partially
      opens up and then the complete linker movement takes place followed by the
      complete opening of the AAA1 domain. In the opening transition, we have observed
      two intermediate states from our simulations where the AAA1 domain is partially
      opened. However, in one state the linker is at a closed position and in the other
      the linker is at an open position. The existence of such intermediates (Pi
      released, ADP bound state) of dynein has been suggested by numerous experimental
      studies earlier. Finally, we discuss the biological relevance of this sequence of
      events in terms of processivity and efficiency of the cycle. The current study
      also shows how the basic principle of protein folding can be extended to
      understand complex phenomena like the stepping mechanism of motor proteins.

PMID- 27886289
TI  - Hydration in silica based mesoporous materials: a DFT model.
AB  - The MCM-41 material is very commonly used as a support for catalysts. However,
      theoretical investigations are significantly limited due to the lack of
      appropriate models that well and accurately describe the real material and enable
      effective computation at the same time. In this work, our aim is to obtain
      calculable models at the DFT level of MCM-41 which are as close as possible to
      the real material. In particular the hydration degree has been investigated, and
      we present and characterize here for the first time a model for the MCM-41 unit
      cell filled with explicit solvent water molecules. This is particularly
      important, because the models developed here are aimed to be further applied in
      theoretical ab initio/DFT studies of adsorption or as a support for modelling
      active sites in catalysts.

PMID- 27886290
TI  - Diffusion-controlled alteration of inhomogeneous materials: tailoring of the
      spatial distribution of nanoparticles in nanocomposites.
AB  - Gaining control over the spatial distribution of nanoparticles in composite
      polymer materials is a relevant goal for a range of nanotechnology applications.
      Promising methods to produce nanoparticles directly in the polymer matrix rely on
      their self-assembly from the atoms that are generated due to the photodestruction
      of the precursor additive. Such materials are known as photoinduced
      nanocomposites. In this work, we theoretically study the possibility of producing
      tailored nanoparticle distributions in such materials by the local modification
      of their physical properties. For instance, laser irradiation may cause a
      permanent free-volume expansion (laser swelling), which results in a substantial
      change in the diffusivity of the aggregating atoms. The modeling shows that the
      nanoparticles tend to accumulate in the domains where the diffusivity is greater.
      Additionally, the variation of the matrix properties may result in spatial
      modulation of the atom-matrix interaction energy and thus modulation of the atom
      solubility in the matrix. This phenomenon can also affect the NP spatial
      distribution. This paper formulates the problem of the precipitation phase
      transition from the supersaturated solution in a polymer solvent which is
      "frozen" in the spatially nonuniform state. The basic traits of this phenomenon
      are studied by means of an analytical model. Then the NP growth is simulated
      using a lattice model.

PMID- 27886291
TI  - A first-principles study of the preventive effects of Al and Mg doping on the
      degradation in LiNi0.8Co0.1Mn0.1O2 cathode materials.
AB  - First-principles calculations have been used to investigate the effects of Al and
      Mg doping on the prevention of degradation phenomena in Li(Ni0.8Co0.1Mn0.1)O2
      cathode materials. Specifically, we have examined the effects of dopants on the
      suppression of oxygen evolution and cation disordering, as well as their
      correlation. It is found that Al doping can suppress the formation of oxygen
      vacancies effectively, while Mg doping prevents the cation disordering behaviors,
      i.e., excess Ni and Li/Ni exchange, and Ni migration. This study also
      demonstrates that formation of oxygen vacancies can facilitate the construction
      of the cation disordering, and vice versa. Delithiation can increase the
      probabilities of formation of all defect types, especially oxygen vacancies. When
      oxygen vacancies are present, Ni can migrate to the Li site during delithiation.
      However, Al and Mg doping can inhibit Ni migration, even in structures with
      preformed oxygen defects. The analysis of atomic charge variations during
      delithiation demonstrates that the degree of oxidation behavior in oxygen atoms
      is alleviated in the case of Al doping, indicating the enhanced oxygen stability
      in this structure. In addition, changes in the lattice parameters during
      delithiation are suppressed in the Mg-doped structure, which suggests that Mg
      doping may improve the lattice stability.

PMID- 27886292
TI  - Quantum tunneling during interstellar surface-catalyzed formation of water: the
      reaction H + H2O2 -> H2O + OH.
AB  - The final step of the water formation network on interstellar grain surfaces
      starting from the H + O2 route is the reaction between H and H2O2. This reaction
      is known to have a high activation energy and therefore at low temperatures it
      can only proceed via tunneling. To date, however, no rate constants are available
      at temperatures below 200 K. In this work, we use instanton theory to compute
      rate constants for the title reaction with and without isotopic substitutions
      down to temperatures of 50 K. The calculations are based on density functional
      theory, with additional benchmarks for the activation energy using unrestricted
      single-reference and multireference coupled-cluster single-point energies. Gas
      phase bimolecular rate constants are calculated and compared with available
      experimental data not only for H + H2O2 -> H2O + OH, but also for H + H2O2 -> H2
      + HO2. We find a branching ratio where the title reaction is favored by at least
      two orders of magnitude at 114 K. In the interstellar medium this reaction
      predominantly occurs on water surfaces, which increases the probability that the
      two reactants meet. To mimic this, one, two, or three spectator H2O molecules are
      added to the system. Eley-Rideal bimolecular and Langmuir-Hinshelwood
      unimolecular rate constants are presented here. The kinetic isotope effects for
      the various cases are compared to experimental data as well as to expressions
      commonly used in astrochemical models. Both the rectangular barrier and the
      Eckart approximations lead to errors of about an order of magnitude. Finally,
      fits of the rate constants are provided as input for astrochemical models.

PMID- 27886293
TI  - Computational design of high efficiency nonplanar tri-s-triazine-based ambipolar
      host materials for phosphorescent blue emitters.
AB  - A series of nonplanar tri-s-triazine-based molecules were designed, and their
      optical, electronic, and charge transport properties as ambipolar host materials
      for blue electrophosphorescence emitters were explored by density functional
      theory. The influence of the linkage between tri-s-triazine and carbazole,
      diphenylamine and triphenylamine, as well as the influence of a series of
      electron-donating and electron-withdrawing substituents on triplet energy, energy
      level matching and charge transport of the designed molecules was discussed in
      detail. Our results reveal that the molecules under investigation can serve as
      host materials for blue electrophosphorescence emitters. We also predicted the
      mobility of designed molecules with better performance in the P1[combining
      macron] space group. Based on the investigated results, we proposed a rational
      way for the design of host materials for OLEDs, and also expanded the application
      field of tri-s-triazine.

PMID- 27886294
TI  - The formation of H bubbles at small-angle tilt grain boundaries in W films.
AB  - The accumulation of H at the small-angle tilt grain boundary (GB) in the W(001)
      surface is investigated, on the basis of the first-principles calculations. By
      exploring the solution and diffusion behaviors of H at the GB, we find that the
      small-angle GB can capture the H atoms nearby, serving as a nucleation site of H
      bubbles. With the increasing number of trapped H atoms, the GB expands gradually,
      and the GBs can be unripped with an areal density of H up to 5.0 * 1015 H atoms
      per cm2, leading to the formation of H bubbles. Moreover, H2 molecules are
      observed, when the areal density of H atoms in GB is over 6.6 * 1015 atoms per
      cm2. According to our calculations, we propose a possible formation mechanism of
      H bubbles observed in the experiment, which is valuable for improving the service
      performance of W as a plasma-facing material in nuclear fusion reactors.

PMID- 27886295
TI  - Proposing the prospects of Ti3CN transition metal carbides (MXenes) as anodes of
      Li-ion batteries: a DFT study.
AB  - A two-dimensional (2D) transition metal carbonitride (MXenes) with a formula of
      Ti3CN as an anode of a lithium-ion battery (LIB) has been proposed in this work.
      The mechanism of Li+ adsorption and diffusion on the surface of Ti3CN and Ti3CNT2
      (T = F, O, and OH functional groups) was studied to estimate the potential
      application of Ti3CN as an anode material by density functional theory (DFT) and
      DFT+U computations. For Ti3CNT2 (T = O, F, OH), the value of Li diffusion
      barriers is from 0.2 eV to 0.3 eV. On the basis of our results, we can know that
      Li prefers adsorption on the nitrogen side for Ti3CN in the absence of functional
      groups and tends to adsorb on the carbon side for Ti3CNT2 (T = O, F, OH). This
      phenomenon can be explained by Bader charge population analysis. For Ti3CNF2, Li
      F formed a six-membered ring with increasing Li concentration, thereby making the
      system more stable. This work contributes to offering perspectives for
      carbonitride systems (MXenes) as LIB anodes.

PMID- 27886296
TI  - Multiplex miRNA assay using lanthanide-tagged probes and the duplex-specific
      nuclease amplification strategy.
AB  - A multiplex ICP-MS-based miRNA assay with duplex-specific nuclease amplification
      using bifunctional oligonucleotide probes was proposed. A multiplex assay of miR
      141, let-7d, and miR-21 could be achieved simultaneously.

PMID- 27886297
TI  - High-pressure dielectric behavior of BaMoO4: a combined experimental and
      theoretical study.
AB  - In situ impedance measurements were employed to investigate the electrical
      transport properties of BaMoO4 under pressures of up to 20.0 GPa. Two anomalous
      changes in the electrical parameters were found, related to the pressure-induced
      structural phase transitions. The dielectric performance of BaMoO4 was improved
      by pressure. The dispersion in the real part of dielectric constant versus
      frequency weakens with increasing pressure. Based on the first-principles
      calculations, the increases of resistance with increasing pressure in the
      tetragonal and monoclinic phases were mainly caused by the increasing defect
      levels. The decrease of the relative permittivity in the tetragonal phase was
      attributed to pressure-induced strengthening in electronic localization around Mo
      atoms, which hindered the polarization of Mo-O electric dipoles.

PMID- 27886298
TI  - A DFT study of the effect of SO4 groups on the properties of TiO2 nanoparticles.
AB  - We present a study of the optical, electronic, and structural properties of TiO2
      anatase-structured nanoparticles upon adsorption of SO4 groups, which are always
      present on the surface of the particles during the sulfate manufacturing method.
      Structural and electronic properties were studied using the density functional
      theory method (DFT), and optical properties were obtained by time-dependent DFT.
      It was found that SO4 groups alter both the geometric and electronic structure of
      TiO2 nanoparticles and change the photoabsorption characteristics. In particular,
      we find that eta2-O2 type O-O moieties are formed due to the adsorption of 3 and
      4SO4 groups.

PMID- 27886300
TI  - A three-dimensional graphene oxide supramolecular hydrogel for infrared light
      responsive cascade release of two anticancer drugs.
AB  - A three dimensional supramolecular hydrogel consisting of prodrug-modified
      graphene oxide and alpha-cyclodextrin was developed. This hydrogel with a well
      ordered interior microstructure integrated hydrophobic and hydrophilic anticancer
      drugs into a single multifunctional platform, and underwent a gel-sol transition
      leading to cascade release of two drugs in an on-demand fashion upon NIR light
      irradiation.

PMID- 27886299
TI  - DNA nanotechnology for nucleic acid analysis: multifunctional molecular DNA
      machine for RNA detection.
AB  - The Nobel prize in chemistry in 2016 was awarded for 'the design and synthesis of
      molecular machines'. Here we designed and assembled a molecular machine for the
      detection of specific RNA molecules. An association of several DNA strands, named
      multifunctional DNA machine for RNA analysis (MDMR1), was designed to (i) unwind
      RNA with the help of RNA-binding arms, (ii) selectively recognize a targeted RNA
      fragment, (iii) attract a signal-producing substrate and (iv) amplify the
      fluorescent signal by catalysis. MDMR1 enabled detection of 16S rRNA at
      concentrations ~24 times lower than that by a traditional deoxyribozyme probe.

PMID- 27886301
TI  - Palladium-mediated in situ synthesis of an anticancer agent.
AB  - As a novel prodrug activation strategy Pd(0) nanoparticles, entrapped within a
      modular polymeric support, were used in cell culture, to synthesise the
      anticancer agent PP-121 from two non-toxic precursors, thereby inducing cell
      death in the first example of in situ mediated drug synthesis.

PMID- 27886302
TI  - New approach for understanding experimental NMR relaxivity properties of magnetic
      nanoparticles: focus on cobalt ferrite.
AB  - Relaxivities r1 and r2 of cobalt ferrite magnetic nanoparticles (MNPs) have been
      investigated in the aim of improving the models of NMR relaxation induced by
      magnetic nanoparticles. On one hand a large set of relaxivity data has been
      collected for cobalt ferrite MNP dispersions. On the other hand the relaxivity
      has been calculated for dispersions of cobalt ferrite MNPs with size ranging from
      5 to 13 nm, without using any fitting procedure. The model is based on the
      magnetic dipolar interaction between the magnetic moments of the MNPs and the 1H
      nuclei. It takes into account both the longitudinal and transversal contributions
      of the magnetic moments of MNPs leading to three contributions in the relaxation
      equations. The comparison of the experimental and theoretical data shows a good
      agreement of the NMR profiles as well as the temperature dependence.

PMID- 27886303
TI  - Multiple correlations between spin crossover and fluorescence in a dinuclear
      compound.
AB  - Multiple correlations between spin crossover and fluorescence are established in
      a dinuclear compound with fluorescence from d(Fe) + pi(SCN) to pi*(ligand) charge
      transfer and correlation originated from ligand to Fe(ii) energy transfer.

PMID- 27886304
TI  - How far away are iron carbide clusters from the bulk?
AB  - Combining the basin hopping structure searching algorithm and density functional
      theory, the iron carbide clusters, FexCy (x <= 8 and y <= 8), and clusters with
      various stoichiometries (Fe2nCn, Fe3nCn, FenC2n, FenC3n and FenC4n (n = 1-7),
      Fe5nC2n, and Fe4nCn (n = 1-5)) are predicted. The stable structures of iron rich
      carbide clusters are composed of C-C dimers or single C atoms on the surface of
      the clusters, which are remarkably different from their corresponding bulk
      structures, where the carbon atoms are atomically distributed in the iron matrix.
      The most stable carbon rich clusters are highly diverse in topology (bowl,
      basket, plane, shoe, necklace, etc.) with long carbon chains. The Bader charge
      analysis shows that the size effect on iron carbide clusters is an electronic
      tuning. Large carbon-rich clusters appear even under low carbon chemical
      potentials, whereas small iron-rich clusters are only energetically stable in
      high carbon chemical potentials, which indicates that changing the carbon
      chemical potential can tune the morphology (size and stoichiometry) of the iron
      carbide clusters. These results may help us understand the catalytic activity of
      iron and iron carbides in reactions such as the Fischer-Tropsch synthesis and the
      carbon nanotube formation process.

PMID- 27886305
TI  - Dipolar dissociation dynamics in electron collisions with carbon monoxide.
AB  - Dipolar dissociation processes in the electron collisions with carbon monoxide
      have been studied using time of flight (TOF) mass spectroscopy in combination
      with the highly differential velocity slice imaging (VSI) technique. By probing
      ion-pair states, both positive and/or negative ions may be detected. The ion
      yield curve of negative ions provides the threshold energy for the ion-pair
      production. On the other hand, the kinetic energy distributions and angular
      distributions of the fragment anion provide detailed dynamics of the dipolar
      dissociation process. Two ion-pair states have been identified based on angular
      distribution measurements using the VSI technique.

PMID- 27886306
TI  - Experimental evidence for quantum cutting co-operative energy transfer process in
      Pr3+/Yb3+ ions co-doped fluorotellurite glass: dispute over energy transfer
      mechanism.
AB  - Pr3+/Yb3+ doped materials have been widely reported as quantum-cutting materials
      in recent times. However, the question of the energy transfer mechanism in the
      Pr3+/Yb3+ pair in light of the quantum-cutting phenomenon still remains
      unanswered. In view of that, we explored a series of Pr3+/Yb3+ co-doped low
      phonon fluorotellurite glass systems to estimate the probability of different
      energy transfer mechanisms. Indeed, a novel and simple way to predict the
      probability of the proper energy transfer mechanism in the Pr3+/Yb3+ pair is
      possible by considering the donor Pr3+ ion emission intensities and the relative
      ratio dependence in the presence of acceptor Yb3+ ions. Moreover, the observed
      results are very much in accordance with other estimated results that support the
      quantum-cutting phenomena in Pr3+/Yb3+ pairs, such as sub-linear power dependence
      of Yb3+ NIR emission upon visible ~450 nm laser excitation, integrated area of
      the donor Pr3+ ion's visible excitation spectrum recorded by monitoring the
      acceptor Yb3+ ion's NIR emission, and the experimentally obtained absolute
      quantum yield values using an integrating sphere setup. Our results give a simple
      way of estimating the probability of an energy transfer mechanism and the factors
      to be considered, particularly for the Pr3+/Yb3+ pair.

PMID- 27886307
TI  - A simple guiding principle for the temperature dependence of the solubility of
      light gases in imidazolium-based ionic liquids derived from molecular
      simulations.
AB  - We have determined the temperature dependence of the solvation behavior of a
      large collection of important light gases in imidazolium-based ionic liquids with
      the help of extensive molecular dynamics simulations. The motivation of our study
      is to unravel common features of the temperature dependent solvation under well
      controlled conditions, and to provide a guidance for cases, where experimental
      data from different sources disagree significantly. The solubility of molecular
      hydrogen, oxygen, nitrogen, methane, krypton, argon, neon and carbon dioxide in
      the imidazolium based ionic liquids of type 1-n-alkyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([Cnmim][NTf2]) with varying alkyl side chain
      lengths n = 2, 4, 6, 8 is computed for a temperature range between 300 K and 500
      K at 1 bar. By applying Widom's particle insertion technique and Bennet's
      overlapping distribution method, we are able to determine the temperature
      dependent solvation free energies of those selected light gases in simulated
      imidazolium based ionic liquids with high statistical accuracy. Our simulations
      demonstrate that the magnitude of the solvation free energy of a gas molecule at
      a chosen reference temperature and that of its temperature-derivatives are
      intimately related to one another. We conclude that this "universal" behavior is
      rooted in a solvation entropy-enthalpy compensation effect, which seems to be a
      defining feature of the solvation of small molecules in ionic liquids. The
      observations lead to simple analytical relations, determining the temperature
      dependence of the solubility data based on the absolute solubility at a certain
      reference temperature. By comparing our results with available experimental data
      from many sources, we can show that our approach is particularly helpful for
      providing reliable estimates for the solvation behavior of very light gases, such
      as hydrogen, where conflicting experimental data exist.

PMID- 27886308
TI  - Impact of the molecular structure and adsorption mode of D-pi-A dye sensitizers
      with a pyridyl group in dye-sensitized solar cells on the adsorption equilibrium
      constant for dye-adsorption on TiO2 surface.
AB  - D-pi-A dyes NI-4 bearing a pyridyl group, YNI-1 bearing two pyridyl groups and
      YNI-2 bearing two thienylpyridyl groups as the anchoring group on the TiO2
      surface have been developed as dye sensitizers for dye-sensitized solar cells
      (DSSCs), where NI-4 and YNI-2 can adsorb onto the TiO2 electrode through the
      formation of the coordinate bond between the pyridyl group of the dye and the
      Lewis acid site (exposed Tin+ cations) on the TiO2 surface, but YNI-1 is
      predominantly adsorbed on the TiO2 electrode through the formation of the
      hydrogen bond between the pyridyl group of the dye and the Bronsted acid sites
      (surface-bound hydroxyl groups, Ti-OH) on the TiO2 surface. The difference in the
      dye-adsorption mode among the three dyes on the TiO2 surface has been
      investigated from the adsorption equilibrium constant (Kad) based on the Langmuir
      adsorption isotherms. It was found that the Kad values of YNI-1 and YNI-2 are
      higher than that of NI-4, and more interestingly, the Kad value of YNI-2 is
      higher than that of YNI-1. This work demonstrates that that for the D-pi-A dye
      sensitizers with the pyridyl group as the anchoring group to the TiO2 surface the
      number of pyridyl groups and the dye-adsorption mode on the TiO2 electrode as
      well as the molecular structure of the dye sensitizer affect the Kad value for
      the adsorption of the dye to the TiO2 electrode, that is, resulting in a
      difference in the Kad value among the D-pi-A dye sensitizers NI-4, YNI-1 and YNI
      2.

PMID- 27886309
TI  - Expeditious trifluoromethylthiolation and trifluoromethylselenolation of
      alkynyl(phenyl)iodoniums by [XCF3]- (X = S, Se) anions.
AB  - Trifluoromethylthiolation and trifluoromethylselenolation of
      alkynyl(phenyl)iodonium tosylates by [XCF3]- (X = S, Se) ions was accomplished in
      5-10 minutes at room temperature under a N2 atmosphere and provided a variety of
      alkynyl trifluoromethyl sulfides and selenides in good yields. Compared to the
      known methods, this approach has several advantages such as short reaction times
      and metal- and additive-free conditions without needing excess [Me4N][XCF3]
      reagents. Moreover, the less efficient reactions of
      (phenylethynyl)benziodoxol(on)e with [Me4N][XCF3] under the standard conditions
      demonstrate that acyclic alkynyl(phenyl)iodoniums are more powerful alkynyl
      sources in the conversion. This protocol allows for a fast and convenient access
      to numerous alkynyl trifluoromethyl sulfides and selenides.

PMID- 27886310
TI  - Positive and negative linear compressibility and electronic properties of
      energetic and porous hybrid crystals with nitrate anions.
AB  - The structural and electronic properties of energetic nitrates with organic
      cations (uronium and 3,3'-diamino-4,4'-azo-1,2,4-triazole) and a metal-organic
      framework crystal [Ag(ethylenediamine)]NO3 have been investigated using density
      functional theory including van der Waals interactions. It is found that the
      linear compressibility of urea nitrate is positive and anisotropic (a ~ b < c),
      whereas 3,3'-diamino-4,4'-azo-1,2,4-triazole nitrate and [Ag(ethylenediamine)]NO3
      show both positive and negative linear compressibility along the b, c and a-axes,
      respectively. Negative linear compressibility is correlated with the expansion of
      hydrogen bonds. The band gaps of considered crystals are different, which is
      related to the difference in the nature (anionic, cationic or mixed) of upper
      valence and lower unoccupied electronic states. The band gap of 3,3'-diamino-4,4'
      azo-1,2,4-triazole nitrate is the smallest and nonlinearly decreases with
      pressure.

PMID- 27886311
TI  - Flexible synthesis of cationic peptide-porphyrin derivatives for light-triggered
      drug delivery and photodynamic therapy.
AB  - Efficient syntheses of cell-penetrating peptide-porphyrin conjugates are
      described using a variety of bioconjugation chemistries. This provides a flexible
      means to convert essentially hydrophobic tetrapyrolle photosensitisers into
      amphiphilic derivatives which are well-suited for use in light-triggered drug
      delivery by photochemical internalisation (PCI) and targeted photodynamic therapy
      (PDT).

PMID- 27886313
TI  - Insights into enhanced visible-light photocatalytic activity of C60 modified g
      C3N4 hybrids: the role of nitrogen.
AB  - Recent experiments have shown that the photocatalytic activity of g-C3N4 can be
      greatly enhanced by C60 modification, however, a fundamental understanding of its
      mechanistic operation is still lacking. Using first-principles calculations, the
      interfacial effects of C60/g-C3N4 nanocomposites on the electronic properties,
      charge transfer and optical response have been explored in detail. For different
      stacking patterns, the two constituents are always linked by van der Waals (vdW)
      forces without any exception, and form type-II heterojunctions in most cases. The
      valence band maximum and conduction band minimum of these heterostructures are
      dominated by the unsaturated nitrogen (N2) atoms and C60 molecule, respectively,
      which strongly interact with each other, resulting in strong charge transfer
      between the two involved constituents and an obvious bending of the g-C3N4
      sheets. The unsaturated N2 atoms included in the interfaces have a significant
      influence on promoting the photocatalytic performance, while the existence of
      saturated nitrogen (N1 and N3) atoms lying in the interfaces will weaken the
      interfacial interactions between C60 molecules and the g-C3N4 monolayers.
      Moreover, the sensitive optical response and satisfactory type-II band alignment
      clearly show that the C60/g-C3N4 heterostructure is an outstanding photocatalyst
      for hydrogen production. We proposed a deep insight (the role of nitrogen) into
      understanding the improved photocatalytic ability of the C60/g-C3N4
      nanocomposites, which may contribute to the rational design of both C60/g-C3N4
      and g-C3N4-based nanocomposite photocatalysts.

PMID- 27886314
TI  - Contrasting tunability of quinizarin fluorescence with p-sulfonatocalix[4,6]arene
      hosts.
AB  - This study reveals the intriguing modulations in the photophysics of quinizarin
      (QZ) on its interaction with p-sulfonatocalix[4]arene (SCX4) and p
      sulfonatocalix[6]arene (SCX6) hosts. While the SCX6-QZ system shows the usual
      reduction in both fluorescence intensity and lifetime, the SCX4-QZ system shows a
      contrasting effect of enhancement in the fluorescence intensity and reduction in
      the fluorescence lifetime. Such a contrasting effect is not only unusual but also
      observed for the first time for any host-guest system. The observed results are
      justifiably correlated with the changes in both radiative and nonradiative decay
      rate constants for the SCX4-QZ system.

PMID- 27886312
TI  - Standardisation of a European measurement method for the determination of anions
      and cations in PM2.5: results of field trial campaign and determination of
      measurement uncertainty.
AB  - European Committee for Standardisation (CEN) Technical Committee 264 'Air
      Quality' has recently produced a standard method for the measurements of anions
      and cations in PM2.5 within its Working Group 34 in response to the requirements
      of European Directive 2008/50/EC. It is expected that this method will be used in
      future by all Member States making measurements of the ionic content of PM2.5.
      This paper details the results of a field measurement campaign and the
      statistical analysis performed to validate this method, assess its uncertainty
      and define its working range to provide clarity and confidence in the
      underpinning science for future users of the method. The statistical analysis
      showed that, except for the lowest range of concentrations, the expanded combined
      uncertainty is expected to be below 30% at the 95% confidence interval for all
      ions except Cl-. However, if the analysis is carried out on the lower
      concentrations found at rural sites the uncertainty can be in excess of 50% for
      Cl-, Na+, K+, Mg2+ and Ca2+. An estimation of the detection limit for all ions
      was also calculated and found to be 0.03 MUg m-3 or below.

PMID- 27886315
TI  - Cellular membrane-anchored fluorescent probe with aggregation-induced emission
      characteristics for selective detection of Cu2+ ions.
AB  - The exploration of advanced fluorescent probes that can detect divalent copper
      (Cu2+) in aqueous environments and even in live organisms is particularly
      valuable for understanding the occurrence and development of Cu2+-related
      diseases. In this work, we report the design and synthesis of an aggregation
      induced emission luminogen (AIEgen)-based probe (TPE-Py-EEGTIGYG) by integrating
      an AIEgen, TPE-Py, with a peptide, EEGTIGYG, which can selectively detect Cu2+ in
      both aqueous solution and live cells. Peptide EEGTIGYG has dual functionality in
      the probe design, namely improving water solubility and providing specific cell
      membrane-binding ability. TPE-Py-EEGTIGYG can self-assemble into nanoaggregates
      at high concentration in aqueous solution (e.g., 25 MUM), which possess large
      fluorescence output due to the restriction of intramolecular rotation of the
      phenyl rings on TPE-Py. The fluorescence of the TPE-Py-EEGTIGYG nanoaggregates
      can be significantly quenched by Cu2+ but not by other metal ions, achieving the
      selective detection of Cu2+ in aqueous media. Furthermore, TPE-Py-EEGTIGYG can
      exist as a molecular species and is very weakly fluorescent in dilute aqueous
      solution (e.g., 5 MUM), but can however largely switch on its fluorescence upon
      specifically anchoring onto the cell membrane. The emissive probes on the cell
      membrane can be used for the detection of Cu2+ ions that move in and out of cells
      with a fluorescence "turn-off" mode.

PMID- 27886316
TI  - The mechanism of large second harmonic generation enhancement activated by Zn2+
      substitution.
AB  - Substitution is an effective method to create new nonlinear optical (NLO)
      materials with an enhanced second harmonic generation (SHG) response. However,
      the large SHG enhancement caused by the substitution of Mg2+ for Zn2+ in an
      isostructural system is rare and has not been investigated yet. Here we elucidate
      the contribution of Zn2+ with d10 electronic configuration to the SHG response
      based on two isostructural silicates Sr2MSi2O7 (M = Zn and Mg). The powder SHG
      measurements show that the SHG response of Sr2ZnSi2O7 is approximately 35 times
      that of alpha-SiO2 and 7 times higher than its isostructural compound Sr2MgSi2O7.
      The calculated band structures reveal that the difference in band gaps is minute
      and the sp hybridization between 4s-orbitals of Zn and 2p-orbitals of O is
      stronger than that between 3s-orbitals of Mg and 2p-orbitals of O. The
      significantly enhanced SHG response of Sr2ZnSi2O7 can be interpreted by the
      enhanced inter-band dipole resulting from strong sp hybridization between Zn and
      O. This provides a route to design new materials with enhanced NLO properties in
      the isostructural system.

PMID- 27886317
TI  - Nanoscale thermal cloaking in graphene via chemical functionalization.
AB  - Macro-thermal cloaking is typically produced by coordinate transformations, but
      this method is unsuitable for nanostructures. We designed a graphene-based
      nanoscale thermal cloak using a novel mechanism of phonon localization. The
      nanocloak in graphene was produced via the chemical functionalization of
      hydrogen, methyl and hydroxyl using molecular dynamics simulations. The cloaking
      performance was quantified by the ratio of thermal cloaking (RTC). We found that
      the RTC correlated with the functionalization fraction and it has a local maximum
      at a certain width, since the heat flux reduction in the exterior and the
      protected region reversed if the width was excessive. The atomic mass of the
      functional group also correlated with the RTC. Our simulations determined that
      phonon localization occurred due to sp2-to-sp3 bonding transitions, which caused
      the heat flux to avoid the transition region. Finally, the extent of phonon
      localization was related to the cloaking performance.

PMID- 27886318
TI  - Site-specific covalent capture of human O6-alkylguanine-DNA-alkyltransferase
      using single-stranded intrastrand cross-linked DNA.
AB  - A methodology is reported to conjugate human O6-alkylguanine-DNA-alkyltransferase
      (hAGT) to the 3'-end of DNA in excellent yields with short reaction times by
      using intrastrand cross-linked (IaCL) DNA probes. This strategy exploited the
      substrate specificity of hAGT to generate the desired DNA-protein covalent
      complex. IaCL DNA linking two thymidine residues, or linking a thymidine residue
      to a 2'-deoxyguanosine residue (either in a 5'->3' or 3'->5' fashion), lacking a
      phosphodiester linkage at the cross-linked site, were prepared using a
      phosphoramidite strategy followed by solid-phase synthesis. All duplexes
      containing the model IaCL displayed a reduction in thermal stability relative to
      unmodified control duplexes. The O4-thymidine-alkylene-O4-thymidine and the (5'
      >3') O6-2'-deoxyguanosine-alkylene-O4-thymidine IaCL DNA adducts were not
      repaired by any of the AGTs evaluated (human AGT and Escherichia coli homologues,
      OGT and Ada-C). The (5'->3') O4-thymidine-alkylene-O6-2'-deoxyguanosine IaCL DNA
      containing a butylene or heptylene tethers were efficiently repaired by the human
      variant, whereas Ada-C was capable of modestly repairing the heptylene IaCL
      adduct. The IaCL strategy has expanded the toolbox for hAGT conjugation to DNA
      strands, without requiring the presence of a complementary DNA sequence. Finally,
      hAGT was functionalized with a fluorescently-labelled DNA sequence to demonstrate
      the applicability of this conjugation method.

PMID- 27886319
TI  - White polymer light emitting diodes based on PVK: the effect of the electron
      injection barrier on transport properties, electroluminescence and controlling
      the electroplex formation.
AB  - The effects of the electron injection barrier on the charge transport, brightness
      and the electroluminescence (EL) properties of polymer light emitting diodes
      (PLEDs) with poly(9-vinylcarbazole) (PVK) as an emissive layer have been studied.
      By using Al and LiF/Al as the cathode in single layer PLEDs and diverse electron
      transporting layers (ETLs) such as 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline
      (BCP), 4,7-diphenyl-1,10-phenanthroline (BPhen) and 2,2',2''-(1,3,5-benzinetriyl)
      tris(1-phenyl-1-H-benzimidazole) (TPBi) in the case of multilayer PLEDs, the
      charge transport, brightness, color tuning and the EL properties of the devices
      were drastically modified. The energy barrier for electrons affects the electron
      current flowing through the device, thereby affecting the operating voltage and
      the brightness of the PLEDs. The PLEDs with TPBi as the ETL possess the lowest
      injection barrier and give the maximum brightness of 426.24 cd m-2. The electron
      injection barrier is also found to play a major role in defining the EL spectra
      of the PLEDs. A larger injection barrier gives rise to electroplex formation in
      the EML-ETL interface of the PLEDs and an additional peak at ~605 nm was observed
      in the EL spectrum. As a result, a near white emission with CIE coordinates of
      (0.30, 0.30) and (0.25, 0.23) at 20 V was obtained from devices with BCP and
      BPhen as ETLs. Furthermore, PVK doped with 2-phenyl-5-(4-biphenylyl)-1,3,4
      oxadiazole (PBD) at 10, 20 and 30 wt% ratios modified the electron transport
      nature of PVK and had a remarkable influence on the aforesaid properties,
      especially on the electroplex formation.

PMID- 27886320
TI  - A palladium and gold catalytic system enables direct access to O- and S-linked
      non-natural glyco-conjugates.
AB  - Here we report a straightforward cross-coupling method for the synthesis of non
      natural glycoamino acids from alkyne-bearing monosaccharides and p
      iodophenylalanine. Pd/Au-catalyzed Sonogashira coupling is tolerant to both O-
      and S-glycosides without any epimerization. In addition, no racemization of the
      amino acid was observed allowing direct access to the homogeneous glyco-conjugate
      in a single step. Notably, this Pd/Au catalytic system presents enhanced
      catalytic activity than conventional Pd/Cu and Pd-only platforms, and it further
      enables the convergent synthesis of glycodipeptides.

PMID- 27886321
TI  - Ion pairing controls rheological properties of "processionary" polyelectrolyte
      hydrogels.
AB  - We demonstrated recently that polyelectrolytes with cationic moieties along the
      chain and a single anionic head are able to form physical hydrogels due to the
      reversible nature of the head-to-body ionic bond. Here we generate a variety of
      such polyelectrolytes with various cationic moieties and counterion combinations
      starting from a common polymeric platform. We show that the rheological
      properties (shear modulus, critical strain) of the final hydrogels can be
      modulated over three orders of magnitude depending on the cation/anion pair. Our
      data fit remarkably well within a scaling model involving a supramolecular head
      to-tail single file between cross-links, akin to the behaviour of pine
      processionary caterpillar. This model allows the quantitative measure of the
      amount of counterion condensation from standard rheology procedure.

PMID- 27886322
TI  - The electronic structure and spin states of 2D graphene/VX2 (X = S, Se)
      heterostructures.
AB  - The structural, magnetic and electronic properties of 2D VX2 (X = S, Se)
      monolayers and graphene/VX2 heterostructures were studied using a DFT+U approach.
      It was found that the stability of the 1T phases of VX2 monolayers is linked to
      strong electron correlation effects. The study of vertical junctions comprising
      of graphene and VX2 monolayers demonstrated that interlayer interactions lead to
      the formation of strong spin polarization of both graphene and VX2 fragments
      while preserving the linear dispersion of graphene-originated bands. It was found
      that the insertion of Mo atoms between the layers leads to n-doping of graphene
      with a selective transformation of graphene bands keeping the spin-down Dirac
      cone intact.

PMID- 27886323
TI  - Sulfur doped reduced graphene oxides with enhanced catalytic activity for oxygen
      reduction via molten salt redox-sulfidation.
AB  - A spontaneous redox reaction of reduced graphene oxide (rGO) in molten Li2CO3
      Na2CO3-K2CO3 with a small amount of Li2SO4 at 550  degrees C was applied to
      synthesize sulfur and sulfur-cobalt doped rGOs (S-rGO/S-Co-rGO). The obtained S
      rGOs and S-Co-rGOs show enhanced catalytic activity for the oxygen reduction
      reaction (ORR) in alkaline aqueous solutions. The onset reduction potential and
      the half-wave potential of S-Co-rGO are 60 and 40 mV more positive than those of
      the original rGO, respectively. The reduction current density of S-Co-rGO
      increases by nearly five times. This study provides a green and continuous molten
      salt doping approach for the fabrication of heteroatom-doped graphene with
      excellent catalytic activity for the ORR.

PMID- 27886324
TI  - Shape-controlled syntheses of metal oxide nanoparticles by the introduction of
      rare-earth metals.
AB  - Here, we report the size- and shape-controlled synthesis of metal oxide
      nanoparticles through the introduction of rare-earth metals. The addition of
      gadolinium oleate in the synthesis of iron oxide nanoparticles induced sphere-to
      cube shape changes of nanoparticles and generated iron oxide nanocubes coated
      with gadolinium. Based on experimental investigations and density functional
      theory (DFT) calculations, we attribute the shape change to the facet-selective
      binding of undecomposed gadolinium oleates. While many previous studies on the
      shape-controlled syntheses of nanoparticles rely on the stabilization of specific
      crystal facets by anionic surfactants or their decomposition products, this study
      shows that the interaction between growing transition metal oxide nanoparticles
      and rare-earth metal complexes can be used as a robust new mechanism for shape
      controlled syntheses. Indeed, we demonstrated that this approach was applicable
      to other transition metal oxide nanoparticles (i.e., manganese oxide and
      manganese ferrite) and rare earth metals (i.e., gadolinium, europium, and
      cerium). This study also demonstrates that the nature of metal-ligand bonding can
      play an important role in the shape control of nanoparticles.

PMID- 27886325
TI  - The intrinsic strength of the halogen bond: electrostatic and covalent
      contributions described by coupled cluster theory.
AB  - 36 halogen-bonded complexes YXARm (X: F, Cl, Br; Y: donor group; ARm acceptor
      group) have been investigated at the CCSD(T)/aug-cc-pVTZ level of theory. Binding
      energies, geometries, NBO charges, charge transfer, dipole moments, electrostatic
      potential, electron and energy density distributions, difference density
      distributions, vibrational frequencies, local stretching and bending force
      constants, and relative bond strength orders n have been calculated and used to
      order the halogen bonds according to their intrinsic strength. Halogen bonding is
      found to arise from electrostatic and strong covalent contributions. It can be
      strengthened by H-bonding or lone pair delocalization. The covalent character of
      a halogen bond increases in the way 3c-4e (three-center-four-electron) bonding
      becomes possible. One can characterize halogen bonds by their percentage of 3c-4e
      bonding. FCl-phosphine complexes can form relatively strong halogen bonds
      provided electronegative substituents increase the covalent contributions in form
      of 3c-4e halogen bonding. Binding energies between 1 and 45 kcal mol-1 are
      calculated, which reflects the large variety in halogen bonding.

PMID- 27886326
TI  - Molecular dynamics simulation of amino acid ionic liquids near a graphene
      electrode: effects of alkyl side-chain length.
AB  - Electric double layer (EDL) supercapacitors, using ionic liquid electrolytes,
      have been receiving a great deal of attention in response to the growing demand
      for energy storage systems. In the present study, the nanoscopic structure of
      amino acid ionic liquids (AAILs) as biodegradable electrolytes near a neutral
      graphene surface was studied by molecular dynamics (MD) simulation. In order to
      explore the influence of the anion type and structure, the effect of the alkyl
      side-chain length of amino acids on the EDL was investigated. The results for the
      AAILs, composed of 1-ethyl-3-methylimidazolium ([EMIM]) cations near alanine
      ([ALA]) and isoleucine ([ILE]) anions, were compared to a conventional
      electrolyte, [EMIM][PF6]. A lower mobility of AAIL compared to [EMIM][PF6], with
      diffusions as low as 10-11 m2 s-1, was observed. The structural results
      demonstrated a layered structure near the surface and most of the adsorbed
      imidazolium cation rings lay flat on the graphene surface. Both MD and quantum
      computations were performed to shed light on the charge behavior of AAIL
      electrolytes. As the current results demonstrate, an increase in the anion side
      chain length leads to a decrease in both the number of adsorbed ions on the
      surface and the thickness of the first adsorbed layer. More impressively, it was
      observed that a low charge concentration in the EDL of AAILs is due to more side
      side interactions. This remarkable feature could introduce AAILs as more
      efficient electrolyte materials than conventional [EMIM][PF6].

PMID- 27886327
TI  - In situ TEM observation on the interface-type resistive switching by
      electrochemical redox reactions at a TiN/PCMO interface.
AB  - The interface-type resistive switching devices exhibiting bipolar and multi-level
      resistive switching have been considered as the key component for neuromorphic
      device applications. To directly observe the microscopic details of underlying
      electrochemical redox reactions occuring at a metal/oxide interface, we
      implemented in situ resistive switching of TiN/Pr0.7Ca0.3MnO3 (PCMO)/Pt junction
      devices in a transmission electron microscope (TEM). The in situ TEM observations
      directly show that an intermediate reaction layer (TiOxNy), growing and shrinking
      in the thickness range of a few nanometers at the TiN/PCMO interface in response
      to the applied voltage, mainly determines the device resistance by limiting the
      transport of charge carriers via the Poole-Frenkel conduction mechanism. A
      detailed analysis of in situ TEM observations demonstrates that electrochemical
      redox reactions at the TiN/PCMO interface are facilitated by the electric field
      driven drift of oxygen as well as Ti ions with a much stronger influence of the
      oxygen ions. As such, the reaction kinetics are governed by the electric field
      acting across the TiOxNy reaction layer. This layer defines the critical field
      for the onset of switching, which is measured to be of the order of 106 V cm-1, a
      typical value at which the ionic drift velocity starts increasing exponentially
      with the field according to the nonlinear ionic drift model. The present results
      indicate that understanding the nature of the electric field driven drift of ions
      in a nanoscale solid electrolyte is a key to the precise control of the resistive
      switching of metal/insulator/metal junction devices via voltage stimulations.

PMID- 27886328
TI  - Fluorinated alcohol-mediated [4 + 3] cycloaddition reaction of indolyl alcohols
      with cyclopentadiene.
AB  - This paper describes an efficient [4 + 3] cycloaddition reaction of 3
      indolylmethanols with cyclopentadiene in hexafluoroisopropanol (HFIP), which is
      catalyst-free and inexpensive, and offers mild reaction conditions, wide
      substrate scope and convenient workup. This methodology provides the first
      catalyst- and additive-free [4 + 3] cycloaddition reactions of indolyl alcohols,
      offering a green and efficient method for the synthesis of cyclohepta[b]indole
      derivatives.

PMID- 27886329
TI  - Interleukin-8 -251A/T polymorphism and periodontitis susceptibility: a meta
      analysis.
AB  - The -251A/T polymorphism in the anti-inflammatory cytokine interleukin-8 (IL-8)
      gene has been implicated in susceptibility to periodontitis; however, this
      correlation has not been elucidated. In this meta-analysis, we investigated the
      association between the IL-8 -251A/T polymorphism and the risk of periodontitis.
      All eligible case-control studies published until August 2014 were identified and
      extracted from PubMed, Web of Science, EMBASE, China National Knowledge Internet,
      and WanFang databases. The strength of this association was accessed by pooled
      odds ratios (ORs) with 95% confidence intervals (CIs), using either a fixed- or
      random-effect model. Nine case-control studies, including 1811 cases and 2043
      controls, were identified. Overall, no significant associations were found
      between the IL-8 -251A/T polymorphism and the risk of periodontitis. The results
      of the analysis of periodontitis subgroup revealed similarities between chronic
      periodontitis and aggressive periodontitis. An additional analysis based on
      ethnicity revealed an association between the IL-8 -251A/T polymorphism and
      periodontitis among Asians (dominant model, OR = 1.784, 95%CI = 1.130-2.817) and
      a mixed population (AA vs TT, OR = 0.667, 95%CI = 0.471-0.974). The results of
      this meta-analysis suggest that the IL-8 -251A/T polymorphism may increase the
      risk of periodontitis in Asian and mixed populations. However, larger and well
      designed studies are warranted to validate our findings.

PMID- 27886330
TI  - Genetic gains from selection for fiber traits in Gossypium hirsutum L.
AB  - Brazil is among the five largest producers of cotton in the world, cultivating
      the species Gossypium hirsutum L. r. latifolium Hutch. The cultivars should have
      good fiber quality as well as yield. Genetic improvement of fiber traits requires
      the study of the genetic structure of the populations under improvement, leading
      to the identification of promising parent plants. To this end, it is important to
      acquire some information, such as estimates of genetic variance components and
      heritability coefficients, which will support the appropriate choice of the
      breeding strategy to be employed as well as enable the estimation of gains from
      selection. This study aimed to evaluate some agronomic characteristics, such as
      fiber quality and yield, estimating genetic parameters for the purpose of
      predicting earnings. Twelve cultivars of cotton, including four male progenitors
      (CNPA 01-42, BRS Verde, Glandless, and Okra leaf) and eight female progenitors
      (Delta opal, CNPA 7H, Aroeira, Antares, Sucupira, Facual, Precoce 3, and CNPA
      8H), were used in performing crosses according to design I, proposed by Comstock
      and Robinson (1948). The experimental design was a randomized block with four
      replications. We observed genetic variability among all traits as well as higher
      efficiency of selection for the gains related to traits. Our results showed that
      the combined selection presented the highest genetic gains for all traits. For
      fiber length, the female/male selection and the combined selection resulted in
      the highest genetic gain.

PMID- 27886331
TI  - Effect of fragmentation on the natural genetic diversity of Theobroma speciosum
      Willd. ex Spreng. populations.
AB  - Forest fragmentation reduces the effective size of natural populations, isolates
      individuals in the landscape, and, consequently, changes species' mating systems
      by increasing the degree of relatedness between individuals and inbreeding.
      Investigating the impact of habitat degradation on forest fragments helps to
      assess the genetic and ecological consequences of these changes, and allows the
      development of effective and sustainable conservation strategies to manage the
      genetic resources of species living in degraded landscapes. The aim of the
      present study was to assess the genetic diversity of fragmented Theobroma
      speciosum populations using microsatellite markers. Three urban forest fragments
      were selected in the municipality of Alta Floresta, Mato Grosso State, Brazil,
      namely C/E park, J park, and Zoo Botanical park. Seventy-five individuals (25 in
      each fragment) were sampled by collecting their leaves for genomic DNA
      extraction. Polymerase chain reaction amplifications were performed using nine
      polymorphic simple sequence repeat primers, which amplified 84 alleles. The mean
      expected heterozygosity was 0.970, and it was always higher than the observed
      heterozygosity. Analysis of molecular variance revealed that most variability
      occurred within populations (64%) rather than between them (36%). The Structure
      software and an unweighted pair group method with arithmetic mean dendrogram
      revealed three distinct groups, showing that individuals were allocated to their
      correct populations. Genotype number 3 from C/E park, number 45 from J park, and
      number 51 from Zoo Botanical park could be used as stock plants in breeding
      programs, because they were the most dissimilar within the populations studied.
      The high genetic diversity levels detected in all three populations studied
      emphasize the importance of protecting this species in its natural habitat.

PMID- 27886332
TI  - Differential interactions between Curtobacterium flaccumfaciens pv.
      flaccumfaciens and common bean.
AB  - Bacterial wilt of common bean caused by Curtobacterium flaccumfaciens pv.
      flaccumfaciens is an important disease in terms of economic importance. It
      reduces grain yield by colonizing xylem vessels, subsequently impeding the
      translocation of water and nutrients to the superior plant parts. The existence
      of physiological races in C. flaccumfaciens pv. flaccumfaciens has not so far
      been reported. The objective of the present investigation was to identify
      physiological races, evaluate differential interaction, and select resistant
      genotypes of common bean. Initially, 30 genotypes of common bean were inoculated
      with eight isolates exhibiting different levels of aggressiveness, under
      controlled greenhouse conditions. Disease was assessed 15 days after inoculation.
      The existence of differential interactions between C. flaccumfaciens pv.
      flaccumfaciens isolates and common bean genotypes were identified by utilizing
      partial diallel analysis. The most aggressive isolates were BRM 14939 and BRM
      14942 and the least aggressive isolates were BRM 14941 and BRM 14946. The
      genotypes IPA 9, Ouro Branco, and Michelite were selected as more resistant among
      the test isolates. The genotypes IAC Carioca Akyta, BRS Notavel, Perola, IAC
      Carioca Arua, and Coquinho contributed more to the isolate x genotype interaction
      according to the ecovalence method of estimation, and were, therefore, indicated
      as differentials. Based on these results, it was possible to conclude that
      physiological races of the pathogen exist, to select resistant genotypes, and to
      propose a set of differentials.

PMID- 27886333
TI  - Association between the polymorphisms in the ATP-binding cassette genes ABCB1 and
      ABCC2 and the risk of drug-resistant epilepsy in a Chinese Han population.
AB  - Epilepsy is a common disease of the nervous system; approximately 20-30% of all
      patients with epilepsy are reported resistant to antiepileptic drugs. ABCB1 and
      ABCC2 are members of ATP-binding cassette transporter (ABC) family that is
      involved in the excretion of antiepileptic drugs. In this case-control study, we
      have investigated the role of ABCB1 rs1045642 and rs2032582 and ABCC2 rs2273697
      and rs717620 single nucleotide polymorphisms in antiepileptic drug-resistance in
      patients with epilepsy. A total of 254 patients with epilepsy (104 drug-resistant
      and 150 drug-responsive) were recruited from the People's Hospital of Wuhan
      University between March 2013 and April 2014. The correlation between the
      demographic, clinical, and genotypic characteristics of the patients and risk of
      drug resistance was statistically analyzed. Patients with drug-resistant epilepsy
      were more likely to present symptomatic epilepsy (chi2 = 22.29, P < 0.001)
      compared to those with drug-responsive epilepsy. The TT genotype of the ABCB1
      rs717620 polymorphism was associated with a higher risk of drug-resistant
      epilepsy compared to the CC genotype [odds ratio (OR) = 2.97, 95% confidence
      interval (CI) = 1.11-8.29]. The TT genotype of ABCB1 rs717620 was also related
      with an increased risk of drug-resistant epilepsy (OR = 2.64, 95%CI = 1.03-7.13)
      compared to the CC+CT genotype in the recessive model. Thus, our study suggests
      that the ABCC2 rs717620 polymorphism is associated with resistance to
      antiepileptic drugs in Chinese patients with epilepsy.

PMID- 27886334
TI  - Microsatellite loci and genetic structure of artificial populations of Cotesia
      flavipes (Hymenoptera, Braconidae).
AB  - Cotesia flavipes (Cameron) is a parasitoid wasp used in the biological control of
      the sugarcane borer (Diatraea saccharalis) (Fabr., 1794). Studies on the genetic
      diversity of C. flavipes are hampered by the lack of highly polymorphic molecular
      markers. In this report, a set of 11 microsatellite loci were developed from an
      enriched library of C. flavipes. Four microsatellite loci were polymorphic and
      were screened in 212 C. flavipes individuals (183 females and 29 males) that were
      randomly sampled from seven rearing laboratory populations. The number of alleles
      ranged from two to three. The average inbreeding coefficient (FIS) among all
      laboratory populations was 0.120, indicating an excess of homozygotes. The
      average genetic diversity within the laboratory populations was 0.292, which is
      lower than the values reported for wild Cotesia spp populations. Genetic
      diversity was most pronounced within laboratory populations (70 to 90%). Most of
      the observed alleles were fixed or close to fixation. This low overall genetic
      diversity may have originated from a founder effect, i.e., the contribution of a
      small number of individuals (genes and alleles) to the formation of these
      populations. To our knowledge, this study is the first to provide microsatellite
      loci and an analysis of the genetic structure of C. flavipes. Our results suggest
      that new introductions of C. flavipes may increase genetic diversity and improve
      the efficiency of the biological control of D. saccharalis. In addition,
      population structure data could be used to estimate the minimum number of wasps
      to be imported.

PMID- 27886335
TI  - microRNA 421 induces apoptosis of c-33a cervical cancer cells via down-regulation
      of Bcl-xL.
AB  - Cervical cancer is a life-threatening condition. MicroRNAs (miRNAs) can promote
      or inhibit cell death and proliferation. The present study investigated the
      effect of miRNA 421 on the growth and apoptosis of cervical cancer cells. miRNA
      421 and control miRNA were synthesized and transfected into c-33a cervical cancer
      cells. A thiazolyl blue tetrazolium bromide assay, caspase-3 activity, and flow
      cytometry were used to study the effects of miRNA 421 on c-33a cell growth, and
      apoptosis. Small interfering RNA targeting Bcl-xL was synthesized and transfected
      into c-33a cells along with miRNA 421. Bcl-xL expression and cell apoptosis were
      then measured by western blot and flow cytometry, respectively. Transfection of
      miRNA 421 into c-33a cells reduced their growth, promoted their apoptosis
      (measured by increased phosphatidylserine eversion), activated caspase-3, and
      decreased Bcl-xL expression. Silencing and overexpression of Bcl-xL enhanced and
      inhibited miRNA 421-induced apoptosis of c-33a cells, respectively. miRNA 421
      induces c-33a cell apoptosis via down-regulation of Bcl-xL, suggesting that this
      latter might be used as a potential clinical target.

PMID- 27886336
TI  - Comparative transcriptome analysis reveals three potential antiviral signaling
      pathways in lymph organ tissue of the red swamp crayfish, Procambarus clarkii.
AB  - The red swamp crayfish (Procambarus clarkii) is one of the most economically
      important farmed aquatic species in China. Compared with its relatively well
      known antibacterial and antifungal mechanisms, the antiviral mechanism is still
      unclear. We used Illumina-based RNA sequencing and bioinformatic technology to
      obtain high-quality sequence reads from the crayfish lymph organ. A total of 5933
      differentially expressed genes (DEGs) were identified between normal and white
      spot syndrome virus-challenged samples. Of these, 4638 genes were differentially
      upregulated and 1295 differentially downregulated by more than two-fold. The DEGs
      were then mapped to different signaling pathways; the Janus kinase/signal
      transducers and activators of transcription, insulin, and Wnt signaling pathways
      were predicted to be involved in crayfish antiviral innate immunity. These
      results provide new insights into crayfish antiviral immunity mechanisms.

PMID- 27886337
TI  - Determination of the optimal number of markers and individuals in a training
      population necessary for maximum prediction accuracy in F2 populations by using
      genomic selection models.
AB  - Genomic selection is a useful technique to assist breeders in selecting the best
      genotypes accurately. Phenotypic selection in the F2 generation presents with low
      accuracy as each genotype is represented by one individual; thus, genomic
      selection can increase selection accuracy at this stage of the breeding program.
      This study aimed to establish the optimal number of individuals required to
      compose the training population and to establish the amount of markers necessary
      to obtain the maximum accuracy by genomic selection methods in F2 populations. F2
      populations with 1000 individuals were simulated, and six traits were simulated
      with different heritability values (5, 20, 40, 60, 80 and 99%). Ridge regression
      best linear unbiased prediction was used in all analyses. Genomic selection
      models were set by varying the number of individuals in the training population
      (2 to 1000 individuals) and markers (2 to 3060 markers). Phenotypic accuracy,
      genotypic accuracy, genetic variance, residual variance, and heritability were
      evaluated. Greater the number of individuals in the training population, higher
      was the accuracy; the values of genotypic and residual variances and heritability
      were close to the optimum value. Higher the heritability of the trait, higher is
      the number of markers necessary to obtain maximum accuracy, ranging from 200 for
      the trait with 5% heritability to 900 for the trait with 99% heritability.
      Therefore, genomic selection models for prediction in F2 populations must consist
      of 200 to 900 markers of major effect on the trait and more than 600 individuals
      in the training population.

PMID- 27886338
TI  - Frequency of the Val1016Ile mutation on the kdr gene in Aedes aegypti (Diptera:
      Culicidae) in south Brazil.
AB  - Recently, the number of Aedes aegypti foci has increased in west of Santa
      Catarina, south Brazil, which has increased concern regarding mosquito-borne
      disease outbreaks such as dengue fever, Zika virus, and chikungunya. Therefore,
      it is important to monitor genetic resistance to insecticides through "knockdown
      resistance". Homozygosity (Ile/Ile) at position 1016 in the coding region of a
      voltage-dependent sodium channel gene (Nav) may induce resistance to pyrethroid
      insecticides. We evaluated the frequency of these alleles in A. aegypti in west
      Santa Catarina. In total, 349 specimens were obtained from the microregions of
      Joacaba (31), Concordia (35), Chapeco (154), and Sao Miguel do Oeste (129). We
      found that 109 individuals (31.0%) were homozygous for Val/Val, 102 (29.0%) were
      heterozygous for Val/Ile, and 138 (40.0%) were homozygous for Ile/Ile. The allele
      frequencies were similar for Val (0.455) and Ile (0.545). Joacaba and Concordia
      had the highest mutant allele frequencies (0.825 and 0.685, respectively).
      Therefore, these populations should be monitored for increases in pyrethroid
      resistance. The Sao Miguel do Oeste and Chapeco populations had similar
      frequencies of Val and Ile and were not in Hardy-Weinberg equilibrium, suggesting
      that a selection pressure or other evolutionary force has occurred. In
      conclusion, the observed frequency of Ile/Ile homozygous individuals in the
      region studied requires attention, because the implementation of controls using
      pyrethroid may increase the frequency of the mutant allele through the selection
      of resistant populations.

PMID- 27886339
TI  - Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK
      signaling pathway.
AB  - There is high incidence of periodontal disease in high-altitude environments;
      hypoxia may influence the proliferation and clone-forming ability of periodontal
      ligament stem cells (PDLSCs). The MAPK signaling pathway is closely correlated
      with cell proliferation, differentiation, and apoptosis. Thus, we isolated and
      cultured PDLSCs under hypoxic conditions to clarify the impact of hypoxia on
      PDLSC proliferation and the underlying mechanism. PDLSCs were separated and
      purified by the limiting dilution method and identified by flow cytometry. PDLSCs
      were cultured under hypoxic or normoxic conditions to observe their cloning
      efficiency. PDLSC proliferation at different oxygen concentrations was evaluated
      by MTT assay. Expression of p38/MAPK and MAPK/ERK signaling pathway members was
      detected by western blotting. Inhibitors for p38/MAPK or ERK were applied to
      PDLSCs to observe their impacts on clone formation and proliferation. Isolated
      PDLSCs exhibited typical stem cell morphological characteristics, strong
      abilities of globular clone formation and proliferation, and upregulated
      expression of mesenchymal stem cell markers. Stem cell marker expression was not
      statistically different between PDLSCs cultured under hypoxia and normoxia (P >
      0.05). The clone number in the hypoxia group was significantly higher than that
      in the control (P < 0.05). PDLSC proliferation under hypoxia was higher than that
      of the control (P < 0.001). p38 and ERK1/2 phosphorylation in hypoxic PDLSCs was
      markedly enhanced compared to that in the control (P < 0.05). Either P38/MAPK
      inhibitor or ERK inhibitor treatment reduced clone formation and proliferation.
      Therefore, hypoxia enhanced PDLSC clone formation and proliferation by activating
      the p38/MAPK and ERK/MAPK signaling pathways.

PMID- 27886340
TI  - Genetic divergence in a soybean (Glycine max) diversity panel based on agro
      morphological traits.
AB  - Owing to the narrow genetic basis of soybean (Glycine max), the incorporation of
      new sources of germplasm is indispensable when searching for alleles that
      contribute to a greater diversity of varieties. The alternative is plant
      introduction, which may increase genetic variability within breeding programs.
      Multivariate techniques are important tools to study genetic diversity and allow
      the precise elucidation of variability in a set of genotypes of interest. The
      agro-morphological traits of 93 soybean accessions from various continents were
      analyzed in order to assess the genetic diversity present, and to highlight
      important traits. The experimental design was incomplete blocks (Alpha lattice, 8
      x 12) with three replicates. Nine agro-morphological traits were analyzed, and
      principal component analysis and cluster analysis were performed, the latter by
      Ward's method. The dendrogram obtained contained eight subgroups, confirming the
      genetic diversity among the accessions and revealing similarities between 11
      national genotypes. The geographical origin of the accessions was not always
      related to the clusters. The traits evaluated, and the methods used, facilitated
      the distinction and characterization of genotypes between and within groups, and
      could be used in Brazilian soybean breeding programs.

PMID- 27886341
TI  - Clinical efficacy of therapeutic intervention for subclinical hypothyroidism
      during pregnancy.
AB  - This study explored the effects of levothyroxine (L-T4) replacement therapy on
      pregnancy outcomes in patients with subclinical hypothyroidism (SCH). We analyzed
      the effects on pregnancy outcomes with respect to gestational week when the
      desired thyroid-stimulating hormone (TSH) level was reached as well as the length
      of time required to reach the target level during L-T4 treatment. This study
      enrolled 457 patients diagnosed with SCH upon initial thyroid function screening.
      Subjects were assigned to the treatment group (N = 184), and the control group (N
      = 273). Two variables were analyzed in the treatment group: the gestational week
      when the target TSH level was achieved and the length of time required to reach
      the target level during treatment. Based on these criteria, the treatment group
      was further divided into subgroups, including three subgroups based on the time
      required to reach target levels (<4 weeks, 4-8 weeks, and >8 weeks) and
      gestational week when the target TSH level was achieved (before the 12th, between
      the 12th-28th, and after the 28th gestational week). The overall risk of
      complications in the control group was significantly higher than in the treatment
      group (P < 0.05). After L-T4 treatment, the incidences of premature rupture of
      fetal membranes (PROM), gestational diabetes mellitus, fetal macrosomia, and
      postpartum hemorrhage in the group with treatment duration <4 weeks were
      significantly lower than those in the groups with 4-8 and >8 weeks treatment
      duration (P < 0.05). L-T4 treatment can significantly reduce the risks of adverse
      pregnancy outcomes in pregnant women with SCH. The shorter the treatment duration
      required to reach the target TSH level and the earlier the gestational week when
      the target TSH level is achieved through treatment, the lower the incidence of
      complications.

PMID- 27886342
TI  - Genetic variability in three populations of Hypostomus hermanni (Teleostei:
      Loricariidae) found in the basins of Ivai River, Tiete River, and Sapucai-Mirim
      River of Brazil.
AB  - The genetic variability in three populations of Hypostomus hermanni from the
      tributaries of the rivers Ivai (Keller), Tiete (Piracicaba), and Sapucai (Sapucai
      Mirim) was determined using electrophoresis on starch gel. The variability in the
      genes for eight enzymes, namely, aspartate aminotransferase (EC 2.6.1.1), glucose
      6-phosphate isomerase (EC 5.3.1.9), glycerol-3-phosphate dehydrogenase (EC
      1.1.1.8), isocitrate dehydrogenase (EC 1.1.1.42), -lactate dehydrogenase (EC
      1.1.1.27), malate dehydrogenase (EC 1.1.1.37), malate dehydrogenase NADP+ (EC
      1.1.1.40), and phosphoglucomutase (EC 5.4.2.2), was assessed. Three loci with
      seven alleles were obtained in the population of Keller River whereas eight loci
      with 20 alleles and six loci with 16 alleles were present in the populations of
      Piracicaba and Sapucai-Mirim rivers, respectively. Individuals analyzed in the
      three watersheds presented all the detected polymorphic loci. The average
      heterozygosity was 0.0527, 0.1742, and 0.1299 in the Keller, Piracicaba, and
      Sapucai-Mirim River populations, respectively. On the basis of identity values
      and genetic distances, all the three populations were determined to be
      genetically very similar.

PMID- 27886343
TI  - Resistance of soybean genotypes to Sclerotinia sclerotiorum isolates in different
      incubation environments.
AB  - Sclerotinia sclerotiorum is an important soybean pathogen. The objectives of this
      study were to evaluate levels of resistance of soybean genotypes to the fungus,
      and to determine the effects of different incubation environments on host
      resistance and pathogen aggressiveness. Two experiments were conducted using 103
      genotypes from the seed collection of Laboratorio de Desenvolvimento de
      Germoplasma, Universidade Federal de Uberlandia (LAGER-UFU). The first experiment
      was conducted in a greenhouse, and the second in a growth chamber. Inoculations
      were performed by the straw test method using two Brazilian isolates of the
      fungus, one from Uberaba, Minas Gerais, and the other from Jatai, Goias. The
      average stem-lesion length (cm) at 5 days post-inoculation was used to determine
      levels of resistance. Overall, the most resistant genotype was EMGOPA-316, and
      the most susceptible genotype was LAGER-29. Incubation in a growth chamber and
      use of the Jatai isolate generated the most reliable data, and multivariate
      analysis indicated that the genotypes were divergent under the growth chamber
      conditions. Therefore, when studying host resistance of soybean genotypes to S.
      sclerotiorum, it is important to use environmental conditions favorable to the
      fungus and aggressive isolates.

PMID- 27886344
TI  - Genetic diversity among coffee tree progenies Big Coffee VL based on growth
      traits and production.
AB  - In a coffee plantation of a coffee 'Acaia' cultivar (Coffea arabica), on the
      Midwest of Minas Gerais in Capitolio city, a different kind of coffee tree was
      found (1989), possibly due to a mutation. It presented larger leaves and grains
      than those of conventional coffee trees and was named as "Big Coffee VL." The aim
      of this study was to estimate the genetic diversity of Big Coffee VL progenies
      cultivated at Universidade Federal de Lavras, by evaluating growth and production
      traits, based on genetic distances and clusters. The experiment was established
      in a lattice design with 100 progenies of this coffee tree and 23 repetitions.
      Traits evaluated were vigor, plant height, stem diameter, node number of
      plagiotropic branches, pair numbers of plagiotropic branches, and productivity.
      Genetic divergence was evaluated by multivariate procedures: Mahalanobis
      generalized distance, clustering methods, and principal component analysis.
      Genetic distances were estimated using Mahalanobis distance and presented
      variations from 0.04 to 18.70. The most similar progenies were P23 and P29 and
      the most dissimilar progenies were G8 and P14. The progenies were divided into
      three groups, with P14 present as an isolated group. Thus, it was possible to
      observe the existence of genetic variability among the progenies of Big Coffee
      VL, which can be used in breeding programs to increase grain size. Progenies G8
      and P14 presented the highest genetic distance, and were the most suitable for
      future integration of crossings in plant breeding programs.

PMID- 27886345
TI  - Estimation of genetic parameters and selection of high-yielding, upright common
      bean lines with slow seed-coat darkening.
AB  - Slow seed coat darkening is desirable in common bean cultivars and genetic
      parameters are important to define breeding strategies. The aims of this study
      were to estimate genetic parameters for plant architecture, grain yield, grain
      size, and seed-coat darkening in common bean; identify any genetic association
      among these traits; and select lines that associate desirable phenotypes for
      these traits. Three experiments were set up in the winter 2012 growing season, in
      Santo Antonio de Goias and Brasilia, Brazil, including 220 lines obtained from
      four segregating populations and five parents. A triple lattice 15 x 15
      experimental design was used. The traits evaluated were plant architecture, grain
      yield, grain size, and seed-coat darkening. Analyses of variance were carried out
      and genetic parameters such as heritability, gain expected from selection, and
      correlations, were estimated. For selection of superior lines, a "weight-free and
      parameter-free" index was used. The estimates of genetic variance, heritability,
      and gain expected from selection were high, indicating good possibility for
      success in selection of the four traits. The genotype x environment interaction
      was proportionally more important for yield than for the other traits. There was
      no strong genetic correlation observed among the four traits, which indicates the
      possibility of selection of superior lines with many traits. Considering
      simultaneous selection, it was not possible to join high genetic gains for the
      four traits. Forty-four lines that combined high yield, more upright plant
      architecture, slow darkening grains, and commercial grade size were selected.

PMID- 27886346
TI  - Simultaneous selection in beans for stability and high agronomic performance.
AB  - The objective of this study was to select common bean cultivars based on their
      stability for flowering, cycle, insertion of the first pod, grain yield, and high
      agronomic performance. Twenty experiments were carried out between 2000 and 2014,
      during two growing seasons, in Rio Grande do Sul, Brazil. The Eberhart and
      Russel, and Lin and Binns methods, as well as the additive main effect and
      multiplicative interaction (AMMI) method, were used to evaluate the stability of
      flowering, cycle, insertion of the first pod, and grain yield of 10 common
      cultivars in all experiments. The Eberhart and Russel, Lin and Binns, and AMMI
      methods identified the Carioca cultivar as the most stable for insertion of the
      first pod, and the Irai cultivar as the most instable for flowering and cycle.
      The Perola cultivar shows stability for flowering, cycle, and insertion of the
      first pod, and Guapo Brilhante is stable for grain yield, according to the Lin
      and Binns method. Controlled crossing between Perola and Guapo Brilhante is
      recommended for the development of new common bean cultivars with greater
      stability for semi-early cycle, architecture of upright plant, and grain yield.

PMID- 27886347
TI  - Genetic variability of Myzus persicae nicotianae densovirus based on partial NS
      and VP gene sequences.
AB  - We previously described a novel densovirus [Myzus persicae nicotianae densovirus
      (MpnDV)] infecting M. persicae nicotianae (Hemiptera: Aphididae) with 34%
      prevalence. This single-stranded DNA virus has a 5480-nucleotide ambisense genome
      and belongs to the Densovirinae subfamily within the family Parvoviridae. In the
      present study, we estimated the genetic diversity of MpnDV using partial
      nonstructural protein (NS) and capsid protein (VP) gene sequences from 10
      locations in China. First, we identified MpnDV-positive samples by amplifying a
      445-bp fragment with primers MpDVF/MpDVR. Subsequently, we amplified and
      sequenced COI genes with primers MpCOIF/ MpCOIR, and partial NS and VP sequences
      with primers MpnDVF1/MpnDVR1. The respective 655-, 1461-, and 423-bp COI, NS, and
      VP fragments were used to analyze the genetic diversity of MpnDV using MEGA 6.0
      and DnaSP 5.0. The high level of identity shared by all COI sequences (>99%)
      suggested that the aphids sampled were of the same species, and indicated
      population homogeneity across the 10 locations investigated. The nucleotide
      diversity of MpnDV sequences (0.0020 +/- 0.0025) was significantly higher than
      that of the COI genes (0.0002 +/- 0.0005). The pairwise fixation index for MpnDV
      was 0.832, and the total gene flow was 0.05. Phylogenetic analysis revealed that
      the MpnDV haplotypes clustered according to geographical location, except for
      those from the Liaoning and Shanxi provinces. In conclusion, MpnDV demonstrated a
      low level of gene flow and high genetic diversity, suggesting that it is
      vertically transmitted, and implying that endosymbiotic viruses could be used as
      markers in studies of insect population genetics.

PMID- 27886348
TI  - Sample sizes to estimate mean values for tassel traits in maize genotypes.
AB  - Tassel traits are important in maize breeding programs aiming to reduce the size
      and number of branches and maintain satisfactory pollen production in order to
      increase grain yield. The objectives of this study were to determine the sample
      size (number of tassels) required to estimate the mean values for tassel traits
      in maize genotypes and to verify the variability of sample size among genotypes.
      Twenty maize genotypes were evaluated in an experiment carried out in a
      randomized block design with three replicates. Twenty tassels were randomly
      collected in each plot, for a total of 1200 tassels. In each tassel, the
      following traits were measured: peduncle dry matter, branching space dry matter,
      central spike dry matter, tassel dry matter, peduncle length, branching space
      length, central spike length, tassel length, tassel dry matter to tassel length
      ratio, number of primary branches, number of secondary branches, and tassel
      branch number. Measures of central tendency and variability were calculated,
      analysis of variance and mean comparison tests were performed, normality was
      verified, and the sample size was determined. In order to estimate the means with
      the same precision, the sample size for weight traits was greater than that for
      length traits. For tassel traits, 11, 20, and 43 tassels are sufficient to
      estimate the mean with a precision of 40, 30, and 20%, respectively, of the
      estimated mean at a 95% confidence level. These data show that there is sample
      size variability among maize genotypes.

PMID- 27886349
TI  - Development of polymorphic microsatellites for Sillago sihama based on next
      generation sequencing and transferability to Sillago japonica.
AB  - Sillago sihama (Forsskal, 1775), a commercially important marine fishery species
      in the Indo-West Pacific, is being developed as a target species for aquaculture
      and stock enhancement in China. However, due to the limitations of traditional
      isolation methods, the available microsatellite loci, or simple sequence repeats
      (SSRs), of S. sihama lack diversity. We used a stepwise approach including
      Illumina sequencing, primer screening, and SSR marker validation to develop
      diverse SSRs for S. sihama. A total of 853.48 Mb clean sequences were assembled
      with high coverage and sequencing depth, and 27,288 potential SSRs were
      identified. A set of 18 novel SSR markers with four type motifs including 11 di-,
      1 tri-, 5 tetra-, and 1 hexanucleotide repeats were successfully isolated. The
      ranges of number of alleles per locus and observed and expected heterozygosities
      were 5-24, 0.226-0.968, and 0.319-0.950, respectively. The diversity parameters
      exhibited high levels of polymorphism in these 18 loci. Three loci with the
      presence of both null alleles and inbreeding showed significant deviation from
      Hardy-Weinberg equilibrium after Bonferroni correction. Moreover, 13 loci
      developed in S. sihama showed high transferability to the closely related species
      Sillago japonica. The polymorphic SSR markers developed in this study may serve
      as valuable tools for further basic and applied research on the genetic resources
      of S. sihama as well as S. japonica. Our results indicate that this approach,
      based on next-generation sequencing technology, is convenient, cost-effective,
      and suitable for SSR marker isolation in other sillaginid fishes.

PMID- 27886350
TI  - Design of artificial red blood cells using polymeric hydrogel microcapsules:
      hydrogel stability improvement and polymer selection.
AB  - PURPOSE: To improve the stability of pectin-oligochitosan hydrogel microcapsules
      under physiological conditions. METHODS: Two different approaches were examined:
      change of the cross-linker length and treatment of the hydrogel microcapsules
      with 150 Mm CaCl2. Replacement of pectin with alginate was also studied. RESULTS
      AND CONCLUSIONS: It was observed that the molecular weight of the cross-linker
      oligochiotsan had no significant improvement on microcapsule stability. On the
      other hand, the treatment of pectin-oligochitosan microcapsules with Ca2+
      increased the microcapsule stability significantly. Different types of alginate
      were used; however, no red-blood-cell-shaped microcapsules could be produced,
      which is likely due to the charge-density difference between deprotonated pectin
      and alginate polymers.

PMID- 27886352
TI  - Alterations of serum osteocalcin levels in patients with Legg-Calve-Perthes.
AB  - BACKGROUND: Legg-Calve-Perthes disease (LCPD) is a paediatric form of
      osteonecrosis that ultimately heals but will cause femoral head and acetabular
      deformities. The purpose of this study was to investigate the early serum
      measurement of osteocalcin in children with femoral head necrosis compared with
      that of healthy children. METHODS: 20 patients with LCPD (4 girls and 16 boys)
      and 20 healthy volunteers (5 girls and 15 boys) were enrolled. All patients did
      not have additional treatment. Blood samples were obtained from all patients
      preoperatively in the morning. All cases had hip radiographs. The serum levels of
      osteocalcin comparisons between the LCPD patients and the healthy volunteers were
      performed using Wilcoxon signed-rank test. The Spearman rank correlation was used
      to assess correlation between LCPD grade and serum osteocalcin levels.
      Significance was set at p = 0.05. RESULTS: The 20 patients with LCPD (72.75 +/-
      24.92 ng/ml) had significantly higher serum osteocalcin levels compared with the
      healthy group (16.80 +/- 4.04 ng/ml) (p<0.01). Serum osteocalcin levels of
      different LCPD grades were significantly different (Spearman's p = 0.540, p =
      0.014). CONCLUSIONS: We observed a significant correlation between serum
      osteocalcin levels and LCPD. These results may be meaningful in clinical practice
      and to future studies.

PMID- 27886351
TI  - Female primary bladder neck obstruction: role of videourodynamics and treatment
      options in a rare clinical entity.
AB  - INTRODUCTION: Primary female bladder neck obstruction is a rare clinical
      condition characterized by the absence/incomplete bladder neck opening during the
      voiding phase of micturition. METHODS: We present the cases of two women
      complaining dysuria, abdominal straining and sensation of incomplete bladder
      emptying. Videourodynamic evaluation was fundamental for a correct diagnosis.
      RESULTS: Videourodynamic evaluation showed a high detrusor pressure during
      emptying phase, partial use of abdominal strain, very low urine flow rate and
      significant postvoid residual; imaging showed a defect in the physiological
      funneling of the bladder neck, absent or incomplete. The first step therapy is
      represented by oral alpha-blockers and clean intermittent self-catheterization in
      case of high postvoid residual. Surgical operations, such as bladder neck
      incision and resection, represent the last option. CONCLUSIONS: In our
      experience, bladder neck obstruction is a rare condition in women and only a
      complete clinical evaluation associated with videourodynamic study can lead to an
      appropriate diagnosis and treatment.

PMID- 27886353
TI  - Patient-reported outcomes after revision surgery compared to primary total hip
      arthroplasty.
AB  - INTRODUCTION: Patients who undergo either primary or revision total hip
      arthroplasty (THA) mainly expect improvement in pain, function/activity and
      quality of life. The purpose of the study was to measure the degree of short-term
      and medium-term improvement and the differences in patient-reported outcome that
      can be expected in patients undergoing revision THA, compared to patients
      undergoing primary THA. METHODS: In this study, the results of patient-reported
      outcome measurements were compared in 124 matched patients, who underwent
      revision surgery and primary THA between 01/2007 and 12/2009. Assessment was
      performed at short-term and medium-term follow-up and included the WOMAC score,
      the UCLA activity score and EuroQol scores. RESULTS: 6 months after revision THA,
      the mean total WOMAC score improved by 22.1 points, the UCLA activity score by
      0.6 points and the EuroQol-Index by 0.2 points. After primary THA, the
      improvement was 41.4 points on the WOMAC, 1.1 points on the UCLA and 0.3 points
      on the EuroQol-Index. At medium-term follow-up, 3.6 years after revision surgery
      and 2.3 years after primary THA, patients undergoing revision THA showed
      significantly less overall improvement, as well as lower final outcome scores,
      than patients undergoing primary THA. CONCLUSIONS: Patients undergoing revision
      arthroplasty, as well as patients undergoing primary THA, can expect major
      improvement in function, activity and quality of life postoperatively. However,
      overall level of improvement, as well as peak attainable outcome levels, are
      lower after revision surgery than after primary THA. Appropriate information for
      patients who undergo hip revision surgery is necessary in order to avoid
      unrealistic expectations and postoperative dissatisfaction.

PMID- 27886354
TI  - A retrospective analysis of the merits and challenges associated with
      simultaneous bilateral THA using the direct anterior approach.
AB  - INTRODUCTION: 15%-20% of patients presenting for total hip arthroplasty (THA)
      have bilateral disease. While simultaneous bilateral THA is of interest to
      patients and surgeons, debate persists regarding its merits. The majority of
      previous reports on simultaneous bilateral THA involve patients in the lateral
      decubitus position, which require repositioning, prepping and draping, and
      exposure of a fresh wound to pressure and manipulation for the contralateral THA.
      The purpose of this study was to compare complications, component position, and
      financial parameters for simultaneous versus staged bilateral THAs using the
      direct anterior approach (DAA). METHODS: Medical records were reviewed for
      patient demographics, medical history, operative time, estimated blood loss
      (EBL), change in hemoglobin, transfusion, tranexamic acid (TXA) use, length of
      stay (LOS), discharge disposition, leg length discrepancy, acetabular cup
      position, and perioperative complications. Cost and reimbursement data were
      analysed. RESULTS: 44 patients were included in the sequential group and fifteen
      patients in the simultaneous group. Operative time, EBL, hemoglobin drop,
      transfusion rate, and LOS were significantly increased for simultaneous group.
      There was no significant difference in component position, complications, or
      readmissions between groups. Profit per hip was significantly higher for the
      simultaneous group. DISCUSSION: While simultaneous DAA THA presents challenges,
      our results suggest that simultaneous DAA THA may add value to the healthcare
      system without resulting in increased complications compared to sequential hip
      arthroplasty.

PMID- 27886355
TI  - Acetabular spacers in 2-stage hip revision: is it worth it? A single-centre
      retrospective study.
AB  - PURPOSE: The aim of this work is to evaluate an acetabular antibiotic loaded bone
      cement spacer in 2-stage revision surgery as a potential approach able to reduce
      complications during the inter-stage period (i.e. dislocation, acetabular wear),
      as well as simplify 2-stage hip revision surgery and improve hip biomechanics.
      METHODS: We performed a retrospective comparative study and evaluated clinical,
      radiological and surgical data of 71 patients affected by periprosthetic hip
      infection who were treated with 2-stage exchange. 31 patients were treated using
      an acetabular spacer in addition to the femoral (group A) while 40 underwent a
      standard revision surgery (femoral spacer only, group B). RESULTS: Mean time of
      surgery for the first stage was 148 +/- 59 minutes and 142 +/- 45 minutes for
      group A and B respectively; we noted a statistically significant reduction (26
      min, p = 0.015) in the same parameter for the second stage (83 +/- 35 minutes for
      group A and 109 +/- 36 minutes for group B). We observed the following interstage
      complications: 5 femoral spacer dislocations (1 for group A and 4 for group B); 1
      spacer fracture (group B), 1 spacer fracture (group A), 2 periprosthetic
      fractures (group B) and 2 patients with acetabular spacer instability (group B).
      Additionally, we observed a significant improvement in leg length restoration for
      group A (p = 0.03). CONCLUSIONS: Our data show that the acetabular spacer
      technique is able to reduce the interstage complication rate and allow improved
      hip biomechanics restoration.

PMID- 27886356
TI  - Posterior approach to optimise patient-reported outcome from revision hip
      arthroplasty.
AB  - INTRODUCTION: Most total hip arthroplasties (THAs) in the UK are performed
      through a posterior or lateral surgical approach. We aimed to investigate any
      difference in outcome from revision THA according to the approach at primary and
      revision THA surgery. METHODS: A retrospective cohort study of 205 patients who
      underwent revision THA for aseptic loosening. Patients rated their pain from 0-10
      and completed the Self-Administered Patient Satisfaction Scale (SAPS), Oxford Hip
      Score (OHS), WOMAC and Short form-12 questionnaires. RESULTS: 205 patients (209
      hips) from a cohort of 238 patients (243 hips, 86%) were available for analysis.
      The mean follow-up was 5 years (SD 1.71). Grouping by approach 20% (43/209) had
      both primary and revision procedures via a lateral approach, 20% (43/209) had
      their primary surgery via a lateral approach and their revision surgery via a
      posterior approach, whilst 60% (123/209) had both procedures via a posterior
      approach.The WOMAC and OHS were significantly better in patients who had a
      posterior approach for both primary and revision surgery, compared to those that
      did not (OHS p = 0.028, WOMAC p = 0.026). We found no significant differences in
      pain, satisfaction or health-related quality of life between the groups.
      DISCUSSION: Choice of approach for revision hip arthroplasty is influenced by a
      number of factors, but in clinical situations where either a lateral or posterior
      approach could be used, the posterior approach appears to be associated with
      better joint-specific outcomes. Registry data may help further explore the
      associations between surgical approach and the outcome from revision THA.

PMID- 27886358
TI  - Outcomes of total hip replacement in limbs affected by poliomyelitis.
AB  - INTRODUCTION: The outcomes of total hip replacement in patients suffering from
      residual poliomyelitis are poorly covered in the literature. In this
      retrospective study we posed the question of whether total hip replacement
      performed for degenerative hip diseases in limbs with residual poliomyelitis
      could determine satisfactory mid-term clinical and radiographic results, with a
      reasonable complication rate. METHODS: A retrospective study was carried out to
      assess the results of 14 total hip replacements performed on 14 patients with
      residual poliomyelitis on the involved limb from June 1999 to September 2011.
      Average age at the time of surgery was 51 years (range 26-66 years). Mean
      duration of follow-up was 92 months (range 52-156 months). Surgery was performed
      through a direct lateral approach on all hips. All but one were cementless
      implants. RESULTS: 2 implants failed, 1 due to traumatic acetabular fracture 6
      days after surgery, and 1 due to aseptic cup loosening 13 years after surgery.
      Surgery was uneventful in all patients except 1 (7%), who experienced a transient
      sensory sciatic nerve palsy. At the latest follow up Harris Hip Score was 83.3
      (range 72-91) with a marked improvement when compared to preoperative score
      (average 52, range 32-78). No dislocations had occurred. CONCLUSIONS: Total hip
      replacement can be considered a feasible option for hip osteoarthritis in
      patients with limbs affected by residual poliomyelitis. Longer follow-up studies
      are needed to assess the effectiveness of unconstrained total hip replacement in
      polio patients.

PMID- 27886357
TI  - Anterior iliopsoas impingement due to a malpositioned acetabular component -
      effective relief by surgical cup reorientation.
AB  - BACKGROUND: Determining the aetiology of persistent pain following total hip
      arthroplasty (THA) can be challenging. Impingement of the iliopsoas muscle due to
      a malpositioned acetabular component after THA might be a potential cause of
      postoperative groin pain. METHODS: We retrospectively analysed the data of 12
      consecutive patients from our orthopaedic department who underwent cup revision
      for painful iliopsoas impingement after primary THA. RESULTS: Thorough physical
      examination as well as radiological assessment of the included patients revealed
      that malpositioning of the acetabular component provoked iliopsoas
      impingement.The Harris Hip Score and the orientation of the acetabular component
      before and after surgical revision at an average follow-up of 56 months were
      analysed. CONCLUSIONS: We were able to demonstrate that surgical cup revision and
      reorientation resulted in distinctly improved scores and is a feasible option to
      effectively treat persistent iliopsoas impingement due to a malpositioned
      acetabular component following THA.

PMID- 27886359
TI  - Normal population reference values for the Oxford and Harris Hip Scores -
      electronic data collection and its implications for clinical practice.
AB  - BACKGROUND: The aim of this study was to assess whether the Harris Hip Score
      (HHS) and the Oxford Hip Score (OHS) were comparable in normal, healthy,
      pathology-free individuals of different age, gender, ethnicity, handedness and
      nationality. The purpose of this study was to establish normal population values
      for the HHS and OHS using an electronic data collection system. METHODS: 317
      Australian and 310 Canadian citizens with no active hip pain, injury or pathology
      in the ipsilateral hip corresponding to their dominant arm, were evaluated.
      Participants completed an electronically-administered questionnaire and were
      assessed clinically. Chi-square tests, Fisher's exact test and Poisson regression
      models were used where appropriate, to investigate the association between hip
      scores, ethnicity, nationality, gender, handedness and age. RESULTS: There was a
      statistically significant association between the OHS and age (p<0.0001) and the
      HHS and age (p = 0.0006); demonstrating that as age increased, normal hip scores
      decreased. There was no statistically significant association between the HHS and
      gender (p = 0.1389); or HSS and nationality, adjusting for age (p = 0.5698) and
      adjusting for gender (p = 0.6997). There was no statistically significant
      association between the OHS and gender (p = 0.1350). Australians reported a
      statistically significant 4.2% higher overall OHS value compared to Canadians (p
      = 0.0490). There was no statistically significant association between the OHS and
      nationality in age groups 18-79 years. Participants >80 years reported a
      statistically significant association between the OHS and nationality (p<0.0001).
      CONCLUSIONS: Studies using an electronic control group should consider
      differences in gender, age, ethnicity and nationality when using the HHS and OHS
      to assess patient outcomes. This study has established an electronic, normal
      control group for studies using the HHS and OHS. When using the OHS, the control
      group should be sourced from the same country of origin. When using the HHS, the
      control group should be sourced from a pre-established control group within a
      database, without necessarily being sourced from the same country of origin.

PMID- 27886361
TI  - Comparison of anatomic vs. straight femoral stem design in total hip replacement 
      femoral canal fill in vivo.
AB  - INTRODUCTION: The femoral canal fill between an anatomic and a straight
      prosthesis design in cementless total hip arthroplasty (THA) was compared. We
      hypothesised that the anatomic SPS stem has higher proximal fill and lesser
      distal fill than the straight stem. MATERIAL AND METHODS: The femoral canal fill
      was measured on 3 months routine postoperative x-rays at 5 levels of the stem in
      50 consecutive patients, aged 35-83 years, who underwent 56 THA procedures by a
      single surgeon in this hospital. 22 patients received a straight design
      Ceramconcept Global stem, 34 patients received an anatomic design Symbios SPS
      stem. Both anteroposterior (AP) and lateral x-rays were combined to suggest a 3-D
      measurement. RESULTS: On the AP x-rays, the canal fill was significantly higher
      using the anatomic design stem at the proximal measurement levels, and was
      significantly higher at the distal levels using the straight stem. With the AP
      and lateral x-rays combined, the canal fill at the proximal levels was also
      significantly higher in the anatomic groups, nonsignificantly lower at the
      central level and significantly lower at the distal levels. DISCUSSION: In THA
      surgery, achieving high fill at the metaphysis of the femur and less fill at the
      diaphysis has been suggested to result in satisfactory outcome and high stability
      of the prosthesis. This study demonstrated that, compared to straight stem
      design, an anatomically designed stem has a significantly higher metaphyseal
      femoral canal fill.

PMID- 27886360
TI  - High proximal migration in cemented acetabular revisions operated with bone
      impaction grafting; 47 revision cups followed with RSA for 17 years.
AB  - BACKGROUND: Bone impaction grafting is a biologically and mechanically appealing
      option in acetabular revision surgery, allowing restitution of the bone stock and
      restoration of the biomechanics. We analysed differences in proximal migration of
      the revision acetabular components when bone impaction grafting is used together
      with a cemented or an uncemented cup. PATIENTS AND METHODS: 43 patients (47
      hips), revised due to acetabular loosening and judged to have less than 50% host
      bone-implant contact were included. The hips were randomised to either an
      uncemented (n = 20) or a cemented (n = 27) revision cup. Radiostereometry and
      radiography was performed postoperatively, at 3 and 6 months, 1, 2, 3, 5, 7, 10
      and 13 and 17 years postoperatively. Clinical follow-up was performed at 1, 2 and
      5 years postoperatively and thereafter at the same interval as in the
      radiographic follow-up. RESULTS: There were no differences in the base line
      demographic data between the 2 groups. At the last follow-up (17 years) 14 hips
      (10 cemented, 4 uncemented) had been re-revised due to loosening. 3 additional
      cups (1 uncemented and 2 cemented) were radiographically loose. There was a
      higher early proximal migration in the cemented cups. DISCUSSION: Cups operated
      on with cement showed a higher early migration measured with RSA and also a
      higher number of late revisions. The reason for this is not known, but factors
      such as inclusion of cases with severe bone defects, use of smaller bone chips
      and issues related to the impaction technique might have had various degrees of
      influence.

PMID- 27886362
TI  - Balloon-assisted venous access salvage through a thrombosed arteriovenous graft.
AB  - INTRODUCTION: Maintaining vascular access by means of radiological intervention
      has become the mainstay of management of patients with central venous stenoses
      and occlusions (CVO), which can be challenging. We present a case of balloon
      assisted percutaneous puncture of an occluded left subclavian vein, through a
      thrombosed arteriovenous graft, for a tunneled dialysis catheter insertion.
      METHODS: A thrombosed left arm arteriovenous graft was accessed, and the occluded
      left subclavian vein was traversed with 0.018 platform. An 8 mm 0.018 low
      platform balloon was inflated in the left subclavian vein as a target for
      percutaneous puncture to gain direct access into the occluded segment of the
      vein. This access was then used for routine placement of a tunneled left
      subclavian dialysis catheter. RESULTS: Successful placement of a tunneled
      dialysis catheter into an occluded left subclavian vein using a balloon- assisted
      puncture technique, through a thrombosed left-arm arteriovenous graft.
      CONCLUSIONS: Thrombosed arteriovenous grafts are potential access sites into the
      central veins. Balloon-assisted punctures allow vascular access salvage into
      otherwise occluded segments of a central vein; in our case, it allowed access
      into an occluded left subclavian vein for dialysis catheter placement.

PMID- 27886363
TI  - The "dilemma of double lifelines": central venous catheter co-existence with
      transvenous cardiac pacemaker.

PMID- 27886364
TI  - Ultrasound-guided angioplasty for treatment of peripheral stenosis of
      arteriovenous fistula - a single-center experience.
AB  - PURPOSE: In patients with end-stage renal disease, arteriovenous fistulas (AVFs)
      are the access of choice for hemodialysis but are often complicated by stenosis.
      We present single-center experience of 78 ultrasound-guided angioplasty
      procedures for treating peripheral stenoses of AVFs. METHODS: Between January
      2013 and November 2015, 78 angioplasties were performed under ultrasound guidance
      in 53 patients with end-stage renal disease who were referred from dialysis
      centers with low flow rate, difficult cannulation, increased cannulation site
      bleeding, immature or thrombosed AVF. Angioplasties were carried out in the
      presence of a structural lesion in the AVF resulting in at least 50% reduction in
      vein diameter with a blood flow of <250 mL/min or a peak systolic velocity >300
      cm/s. Clinical success, anatomical success and post-intervention primary and
      secondary patency rates at 6, 12, 18 and 24 months were studied. RESULTS: In
      49/53 patients (92.4%), 74 angioplasty procedures were successfully performed,
      whereas 4/53 patients (7.6%) had primary failure. A total of 35/49 patients
      (71.4%) underwent single angioplasty procedure whereas 14/49 patients (28.6%)
      underwent multiple angioplasty procedures. Post-intervention primary patency
      rates at 6, 12, 18 and 24 months were 78.6%, 60.2%, 53.8% and 48.9%,
      respectively. Post-intervention secondary patency rates at 6, 12, 18 and 24
      months were 100%, 100%, 95.4% and 89%, respectively. Clinical success and
      anatomical success was 94.8% and 89.7%, respectively. CONCLUSIONS: Ultrasound
      guided angioplasty is an effective method with good long-term outcomes in
      selected dialysis patients with peripheral stenosis of AVF.

PMID- 27886366
TI  - Utility of blind percutaneous jugular venous cannulation in resource-limited
      settings.
AB  - BACKGROUND: For the nephrologist practicing in resource-limited settings,
      vascular ultrasound is often unavailable; consequently, blind percutaneous
      puncture of large veins is often employed to establish vascular access for
      hemodialysis. METHODS: To examine the efficacy and safety of this approach we
      evaluated 53 consecutive patients in whom central vascular access was required.
      The vascular access route utilized was primarily the right internal jugular vein.
      In the majority of cases, the indication for central vascular access was
      hemodialysis. RESULTS: The average number of needle passes required to obtain
      vascular access was 1.6 for the patient population studied. A total of 90.6% of
      the patients required <=2 needle passes during cannulation. Complication rate for
      the blind approach was low (7.6%) and no serious or life-threatening
      complications occurred. CONCLUSIONS: Our findings suggest that blind percutaneous
      puncture of the internal jugular vein by trained hands is a relatively safe and
      effective approach for establishing vascular access for hemodialysis in resource
      limited settings. Nevertheless, wherever vascular ultrasound is available, it
      should be primarily utilized because of the documented advantages of image-guided
      insertion. Keeping in view the risk of serious peri-procedural complications
      which include death, the emphasis on image-guided insertion, is appropriate,
      particularly, in non-emergent situations.

PMID- 27886365
TI  - The use of ultrasound for peripheral IV placement by vascular access team nurses
      at a tertiary children's hospital.
AB  - PURPOSE: Children receiving treatment in the hospital frequently require
      intravenous (IV) access. Placement of short peripheral catheters can be painful
      and challenging especially in those children who have difficult access. Many
      children's hospitals have teams of specialized vascular access nurses experienced
      in peripheral catheter insertion, and at times use vein visualization devices,
      including ultrasound (US), to assist in peripheral IV placement. Our objectives
      were to describe the prevalence and success rate of US-guided peripheral IV
      placement by vascular access team nurses at a single tertiary children's
      hospital. METHODS: We retrospectively reviewed quality assurance data kept by our
      institution's vascular access team between February, 2014 and March, 2014. Data
      extracted included: age, gender, number of attempts, if difficult, if ultimately
      successful and modality used to aid IV placement. Descriptive statistics and chi
      square tests were used to analyze and report data. RESULTS: There were 1111
      patient-nurse encounters reported for peripheral IV placement over a six-week
      period, and a total of 1579 attempts. Ultimately 84% of the patients had
      successful IV placement. Overall, visualization and palpation was the most
      frequently used technique (50.1%), followed by near-infrared light (40.6%), US
      (8.0%), and transillumination (1.3%). The success rate of US (60% overall and
      59.2% difficult) was not significantly different from other advanced
      visualization techniques. CONCLUSIONS: Vascular access team nurses use US
      infrequently for peripheral IV placement, including in children with difficult
      access. Methods to increase its skillful use in difficult access patients and
      improve successful IV placements should be explored.

PMID- 27886367
TI  - Tissue ischemia worsens during hemodialysis in end-stage renal disease patients.
AB  - BACKGROUND: Cognitive deficit is a common problem in end-stage renal disease
      (ESRD) patients. Ultrafiltration and hemodialysis lead to profound hemodynamic
      changes. The aim of this pilot study was to describe brain and hand oxygenation
      values in ESRD patients and their changes during hemodialysis. METHODS: Twenty
      seven patients treated by chronic hemodialysis and 17 controls patients of the
      same age were included in the study. Regional saturation of oxygen (SrO2) was
      measured at the brain frontal lobe and at the hand with dialysis access using the
      INVOS 5100C. In 17 of ESRD patients, SrO2 was also monitored throughout
      hemodialysis. Finger systolic blood pressure and basic hemodialysis and
      laboratory data were collected. RESULTS: Dialysis patients had lower brain and
      also hand SrO2 values at rest (51.5 +/- 10.9 vs. 68 +/- 7%, p<0.0001 and 55 +/-
      16 vs. 66 +/- 8%, p = 0.03, respectively). Both values further decreased during
      the first 35 minutes of hemodialysis (brain SrO2 to 47 +/- 8%, p<0.0001 and hand
      to 45 +/- 14%, p<0.0001, respectively). The brain SrO2 decrease was related to
      the ultrafiltration rate, the hand SrO2 decrease to the finger pressure and to
      blood hemoglobin. CONCLUSIONS: Chronic dialysis patients suffer from tissue
      ischemia and that even worsens after the beginning of hemodialysis. This
      observation may contribute to the understanding of cognitive deficit etiology.

PMID- 27886368
TI  - Written information for patients (or parents of child patients) to reduce the use
      of antibiotics for acute upper respiratory tract infections in primary care.
AB  - BACKGROUND: Acute upper respiratory tract infections (URTIs) are frequently
      managed in primary care settings. Although many are viral, and there is an
      increasing problem with antibiotic resistance, antibiotics continue to be
      prescribed for URTIs. Written patient information may be a simple way to reduce
      antibiotic use for acute URTIs. OBJECTIVES: To assess if written information for
      patients (or parents of child patients) reduces the use of antibiotics for acute
      URTIs in primary care. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase,
      CINAHL, LILACS, Web of Science, clinical trials.gov, and the World Health
      Organization (WHO) trials registry up to July 2016 without language or
      publication restrictions. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) involving patients (or parents of child patients) with acute URTIs,
      that compared written patient information delivered immediately before or during
      prescribing, with no information. RCTs needed to have measured our primary
      outcome (antibiotic use) to be included. DATA COLLECTION AND ANALYSIS: Two review
      authors screened studies, extracted data, and assessed study quality. We could
      not meta-analyse included studies due to significant methodological and
      statistical heterogeneity; we summarised the data narratively. MAIN RESULTS: Two
      RCTs met our inclusion criteria, involving a total of 827 participants. Both
      studies only recruited children with acute URTIs (adults were not involved in
      either study): 558 children from 61 general practices in England and Wales; and
      269 primary care doctors who provided data on 33,792 patient-doctor consultations
      in Kentucky, USA. The UK study had a high risk of bias due to lack of blinding
      and the US cluster-randomised study had a high risk of bias because the methods
      to allocate participants to treatment groups was not clear, and there was
      evidence of baseline imbalance.In both studies, clinicians provided written
      information to parents of child patients during primary care consultations: one
      trained general practitioners (GPs) to discuss an eight-page booklet with
      parents; the other conducted a factorial trial with two comparison groups
      (written information compared to usual care and written information plus
      prescribing feedback to clinicians compared to prescribing feedback alone).
      Doctors in the written information arms received 25 copies of two-page government
      sponsored pamphlets to distribute to parents.Compared to usual care, we found
      moderate quality evidence (one study) that written information significantly
      reduced the number of antibiotics used by patients (RR 0.53, 95% CI 0.35 to 0.80;
      absolute risk reduction (ARR) 20% (22% versus 42%)) and had no significant effect
      on reconsultation rates (RR 0.79, 95% CI 0.47 to 1.32), or parent satisfaction
      with consultation (RR 0.95, 95% CI 0.87 to 1.03). Low quality evidence (two
      studies) demonstrated that written information also reduced antibiotics
      prescribed by clinicians (RR 0.47, 95% CI 0.28 to 0.78; ARR 21% (20% versus 41%);
      and RR 0.84, 95% CI 0.81 to 0.86; 9% ARR (45% versus 54%)). Neither study
      measured resolution of symptoms, patient knowledge about antibiotics for acute
      URTIs, or complications for this comparison.Compared to prescribing feedback, we
      found low quality evidence that written information plus prescribing feedback
      significantly increased the number of antibiotics prescribed by clinicians (RR
      1.13, 95% CI 1.09 to 1.17; absolute risk increase 6% (50% versus 44%)). Neither
      study measured reconsultation rate, resolution of symptoms, patient knowledge
      about antibiotics for acute URTIs, patient satisfaction with consultation or
      complications for this comparison. AUTHORS' CONCLUSIONS: Compared to usual care,
      moderate quality evidence from one study showed that trained GPs providing
      written information to parents of children with acute URTIs in primary care can
      reduce the number of antibiotics used by patients without any negative impact on
      reconsultation rates or parental satisfaction with consultation. Low quality
      evidence from two studies shows that, compared to usual care, GPs prescribe fewer
      antibiotics for acute URTIs but prescribe more antibiotics when written
      information is provided alongside prescribing feedback (compared to prescribing
      feedback alone). There was no evidence addressing resolution of patients'
      symptoms, patient knowledge about antibiotics for acute URTIs, or frequency of
      complications.To fill evidence gaps, future studies should consider testing
      written information on antibiotic use for adults with acute URTIs in high- and
      low-income settings provided without clinician training and presented in
      different formats (such as electronic). Future study designs should endeavour to
      ensure blinded outcome assessors. Study aims should include measurement of the
      effect of written information on the number of antibiotics used by patients and
      prescribed by clinicians, patient satisfaction, reconsultation, patients'
      knowledge about antibiotics, resolution of symptoms, and complications.

PMID- 27886369
TI  - Genomic data reveals potential for hybridization, introgression, and incomplete
      lineage sorting to confound phylogenetic relationships in an adaptive radiation
      of narrow-mouth frogs.
AB  - The microhylid frog genus Kaloula is an adaptive radiation spanning the edge of
      the Asian mainland and multiple adjacent island archipelagos, with much of the
      clade's diversity associated with an endemic Philippine radiation. Relationships
      among clades from the Philippines, however, remain unresolved. With
      ultraconserved element (UCE) and mitogenomic data, we identified highly supported
      differences in topology and areas of poor resolution, for each marker set. Using
      the UCE data, we then identified possible instances of contemporary
      hybridization, past introgression, and incomplete lineage sorting (ILS) within
      the Philippine Kaloula. Using a simulation approach, and an estimate of the
      Philippine Kaloula clade origin (12.7-21.0 mya), we demonstrate that an
      evolutionary history including inferred instances of hybridization,
      introgression, and ILS leads to phylogenetic reconstructions that show
      concordance with results from the observed mitogenome and UCE data. In the
      process of validating a complex evolutionary scenario in the Philippine Kaloula,
      we provide the first demonstration of the efficacy of UCE data for phylogenomic
      studies of anuran amphibians.

PMID- 27886370
TI  - Epigenetic alterations of the BDNF gene in combat-related post-traumatic stress
      disorder.
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) plays a crucial role in
      modulating resilience and vulnerability to stress. The aim of this study was to
      investigate whether epigenetic regulation of the BDNF gene is a biomarker of post
      traumatic stress disorder (PTSD) development among veterans exposed to combat in
      the Vietnam War. METHODS: Using the Clinician-Administered PTSD Scale, combat
      veterans were grouped into those with (n = 126) and without (n = 122) PTSD. DNA
      methylation levels at four CpG sites within the BDNF promoter I region were
      quantified in the peripheral blood using pyrosequencing. The effects of BDNF DNA
      methylation levels and clinical variables on the diagnosis of PTSD were tested
      using binary logistic regression analysis. RESULTS: Subjects with PTSD showed a
      higher DNA methylation of four CpG sites at the BDNF promoter compared with those
      without PTSD. High methylation levels at the BDNF promoter CpG site, high combat
      exposure, and alcohol problems were significantly associated with PTSD diagnosis.
      CONCLUSIONS: This study demonstrated an association between higher DNA
      methylation of the BDNF promoter and PTSD diagnosis in combat-exposed
      individuals. Our findings suggest that altered BDNF methylation may be a valuable
      biomarker of PTSD after trauma exposure.

PMID- 27886372
TI  - Oxygen for breathlessness in patients with chronic obstructive pulmonary disease
      who do not qualify for home oxygen therapy.
AB  - BACKGROUND: Breathlessness is a cardinal symptom of chronic obstructive pulmonary
      disease (COPD). Long-term oxygen therapy (LTOT) is given to improve survival time
      in people with COPD and severe chronic hypoxaemia at rest. The efficacy of oxygen
      therapy for breathlessness and health-related quality of life (HRQOL) in people
      with COPD and mild or no hypoxaemia who do not meet the criteria for LTOT has not
      been established. OBJECTIVES: To determine the efficacy of oxygen versus air in
      mildly hypoxaemic or non-hypoxaemic patients with COPD in terms of (1)
      breathlessness; (2) HRQOL; (3) patient preference whether to continue therapy;
      and (4) oxygen-related adverse events. SEARCH METHODS: We searched the Cochrane
      Airways Group Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE and Embase, to 12 July 2016, for randomised controlled trials
      (RCTs). We handsearched the reference lists of included articles. SELECTION
      CRITERIA: We included RCTs of the effects of non-invasive oxygen versus air on
      breathlessness, HRQOL or patient preference to continue therapy among people with
      COPD and mild or no hypoxaemia (partial pressure of oxygen (PaO2) > 7.3 kPa) who
      were not already receiving LTOT. Two review authors independently assessed
      articles for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review
      authors independently collected and analysed data. We assessed risk of bias by
      using the Cochrane 'Risk of bias tool'. We pooled effects recorded on different
      scales as standardised mean differences (SMDs) with 95% confidence intervals
      (CIs) using random-effects models. Lower SMDs indicated decreased breathlessness
      and reduced HRQOL. We performed subanalyses and sensitivity analyses and assessed
      the quality of evidence according to the Grading of Recommendations, Assessment,
      Development and Evaluations (GRADE) approach. MAIN RESULTS: Compared with the
      previous review, which was published in 2011, we included 14 additional studies
      (493 participants), excluded one study and included data for meta-analysis of
      HRQOL. In total, we included in this review 44 studies including 1195
      participants, and we included 33 of these (901 participants)in the meta
      analysis.We found that breathlessness during exercise or daily activities was
      reduced by oxygen compared with air (32 studies; 865 participants; SMD -0.34, 95%
      CI -0.48 to -0.21; I2 = 37%; low-quality evidence). This translates to a decrease
      in breathlessness of about 0.7 points on a 0 to 10 numerical rating scale. In
      contrast, we found no effect of short-burst oxygen given before exercise (four
      studies; 90 participants; SMD 0.01, 95% CI -0.26 to 0.28; I2 = 0%; low-quality
      evidence). Oxygen reduced breathlessness measured during exercise tests (25
      studies; 442 participants; SMD -0.34, 95% CI -0.46 to -0.22; I2 = 29%; moderate
      quality evidence), whereas evidence of an effect on breathlessness measured in
      daily life was limited (two studies; 274 participants; SMD -0.13, 95% CI, -0.37
      to 0.11; I2 = 0%; low-quality evidence).Oxygen did not clearly affect HRQOL (five
      studies; 267 participants; SMD 0.10, 95% CI -0.06 to 0.26; I2 = 0%; low-quality
      evidence). Patient preference and adverse events could not be analysed owing to
      insufficient data. AUTHORS' CONCLUSIONS: We are moderately confident that oxygen
      can relieve breathlessness when given during exercise to mildly hypoxaemic and
      non-hypoxaemic people with chronic obstructive pulmonary disease who would not
      otherwise qualify for home oxygen therapy. Most evidence pertains to acute
      effects during exercise tests, and no evidence indicates that oxygen decreases
      breathlessness in the daily life setting. Findings show that oxygen does not
      affect health-related quality of life.

PMID- 27886371
TI  - Why babies die in unplanned out-of-institution births: an enquiry into perinatal
      deaths in Norway 1999-2013.
AB  - INTRODUCTION: The aims were to describe causes of death associated with unplanned
      out-of-institution births, and to study whether they could be prevented. MATERIAL
      AND METHODS: Retrospective population-based observational study based on data
      from the Medical Birth Registry of Norway and medical records. Between 1 January
      1999 and 31 December 2013, 69 perinatal deaths among 6027 unplanned out-of
      institution births, whether unplanned at home, during transportation, or
      unspecified, were selected for enquiry. Hospital records were investigated and
      cases classified according to Causes of Death and Associated Conditions. RESULTS:
      63 cases were reviewed. There were 25 (40%) antepartum deaths, 10 (16%)
      intrapartum deaths, and 24 neonatal (38%) deaths. Four cases were in the unknown
      death category (6%). Both gestational age and birthweight followed a bimodal
      distribution with modes at 24 and 38 weeks and 750 and 3400 g, respectively. The
      most common main cause of death was infection (n = 14, 22%), neonatal (n = 14,
      22%, nine due to extreme prematurity) and placental (n = 12, 19%, seven placental
      abruptions). There were 86 associated conditions, most commonly perinatal (n =
      32), placental (n = 15) and maternal (n = 14). Further classification revealed
      that the largest subgroup was associated perinatal conditions/sub-optimal care,
      involving 25 cases (40%), most commonly due to sub-optimal maternal use of
      available care (n = 14, 22%). CONCLUSIONS: Infections, neonatal, and placental
      causes accounted for almost two-thirds of perinatal mortality associated with
      unplanned out-of-institution births in Norway. Sub-optimal maternal use of
      available care was found in more than one-fifth of cases.

PMID- 27886374
TI  - Effect of Different Aloe Fractions on the Growth of Lactic Acid Bacteria.
AB  - Several foods on the market, such as yogurt and fermented milk, include mixtures
      of prebiotics and probiotic microorganisms effective in promoting the
      proliferation and equilibrium of intestinal bacteria, thus improving gut health.
      Particularly, researchers and the public have shown increasing interest in the
      combination of probiotics with natural substances that promote health or that can
      act as substrates to promote bacterial growth. The aim of this study is to
      evaluate the effects of different extracts of Aloe barbadensis and Aloe
      arborescens in fermented milk, taking into account both the prebiotic effect of
      aloe polysaccharides and the antimicrobial activity of several secondary
      metabolites. The results demonstrate a beneficial effect of 5% aloe inner gel on
      Lactobacillus growth and confirm the antimicrobial activity of the phenolic
      compounds peculiar of green rind extracts.

PMID- 27886375
TI  - Modulation of Chloride Currents in Human Lung Epithelial Cells Exposed to
      Exogenous Oxidative Stress.
AB  - Air pollution continues to be a major public health concern affecting 9 out of 10
      individuals living in urban areas worldwide. Respiratory tract is the organ most
      exposed to gas pollution, and ozone has been shown to be one of the most noxious
      pollutants to which living organisms are exposed. In the present work, we have
      investigated the effects of 0.1 ppm of ozone on chloride currents in human lung
      epithelial cells (A549 line) and whether this effect could be modulated by
      vitamin E pre-treatment. Whole-cell patch clamp technique was applied to not
      excitable cells in order to obtain information about chloride currents behavior,
      important for epithelial lung cells homeostasis. Significant alteration of the I
      V curve after ozone treatment was observed, with the appearance of a large
      outward rectifier component decreasing over time and returning to the basal state
      levels after 24 h. Statistical analysis indicated a modification of the amount of
      ions passing the membrane in the unit of time as a possible cause of this
      difference. RT-qPCR analysis showed an increase in ClC-2 and ORCC mRNA after
      ozone exposure. In addition, pre-treatment with vitamin E was able to suppress
      the outward rectifier component induced by ozone, bringing back the current
      values to the control level and preventing ozone induced chloride channels up
      regulation. Our data suggest that ozone exposure is able to modify chloride
      current density and the use of vitamin E can prevent the above-mentioned damage.
      J. Cell. Physiol. 232: 1817-1825, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27886373
TI  - Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK
      293 cells.
AB  - BACKGROUND AND PURPOSE: Clemizole, a histamine H1 receptor antagonist has a
      potential therapeutic effect on hepatitis C infection and also potently inhibits
      TRPC5 ion channels. The aim of the present study was to investigate whether
      clemizole blocks cardiac K+ currents and thus affects cardiac repolarization.
      EXPERIMENTAL APPROACH: Whole-cell patch techniques was used to examine the
      effects of clemizole on hERG channel current, IKs and Kv 1.5 channel current in
      HEK 293 cell expression systems as well as on ventricular action potentials of
      guinea pig hearts. Isolated hearts from guinea pigs were used to determine the
      effect on the ECG. KEY RESULTS: Clemizole decreased hERG current by blocking both
      open and closed states of the channel in a concentration-dependent manner (IC50 :
      0.07 MUM). The S631A, S636A, Y652A and F656V hERG mutant channels reduced the
      inhibitory effect of clemizole (IC50 : 0.82, 0.89, 1.49 and 2.98 MUM,
      respectively), suggesting that clemizole is a pore blocker of hERG channels.
      Clemizole also moderately decreased IKs and human Kv 1.5 channel current.
      Moreover, clemizole increased the duration of the ventricular action potential in
      guinea pig hearts and the QTc interval in isolated perfused hearts from guinea
      pigs, in a concentration-dependent manner (0.1-1.0 MUM). CONCLUSION AND
      IMPLICATIONS: Our results provide the first evidence that clemizole potently
      blocks hERG channels, moderately inhibits cardiac IKs , delays cardiac
      repolarization and thereby prolongs QT interval. Thus, caution should be taken
      when clemizole is used as a TRPC5 channel blocker or for treating hepatitis C
      infection.

PMID- 27886376
TI  - "The Burden of Pregnancy"; heavier for the heaviest? The changes in Health
      Related Quality of Life (HRQoL) assessed by the 15D instrument during pregnancy
      and postpartum in different body mass index groups: a longitudinal survey.
AB  - INTRODUCTION: Only little information is available on health-related quality of
      life (HRQoL) and its changes during the course of a normal pregnancy. We studied
      changes in HRQoL in a pregnant population during pregnancy and until 1 year
      postpartum in different body mass index (BMI) groups. MATERIAL AND METHODS: Seven
      hundred and fifty pregnant women attending the first ultrasound examination
      before gestational week 14 were invited to participate in a longitudinal,
      communal-based survey. The participants were divided into three groups according
      to their BMI; <25, 25-29.9, and >=30 kg/m2 . The women were asked to fill in
      questionnaires assessing HRQoL (15D), depressive symptoms (Edinburgh Depression
      Scale, EPDS), medical, obstetric and socioeconomic status at baseline. HRQoL and
      EPDS were re-assessed at 30 weeks of gestation, and 6 weeks, 3 and 12 months
      postpartum. RESULTS: Of the invited 750 mothers, 325 (43%) returned the
      questionnaires and at least one follow-up questionnaire. At baseline, mean 15D
      scores decreased with increasing BMI but the difference was not statistically
      significant when adjusted for age, educational attainment, parity or EPDS-scores
      (0.929, 0.921 and 0.916, p = 0.16). During the course of pregnancy, the HRQoL of
      all women decreased but this decrease was significantly greater in the obese
      group (-0.088; 95% CI -0.110 to -0.065) than in the other groups [-0.054 (95% CI 
      0.062 to -0.045) and -0.051 (95% CI -0.068 to -0.033), p = 0.019]. Within 3
      months postpartum the mean HRQoL recovered in all BMI groups to baseline levels,
      irrespective of the mode of delivery or pregnancy-related complications.
      CONCLUSION: The burden of pregnancy is heavier for the heaviest.

PMID- 27886377
TI  - A Kinetic Study of Furan Formation in Wheat Flour-Based Model Systems during
      Frying.
AB  - Furan is a possible human carcinogen, which is formed in worldwide highly
      consumed fried starchy foods. In order to elucidate the mechanisms responsible
      for its occurrence in this food category and propose techniques for its
      mitigation, the kinetics of furan formation, oil absorption, lipid oxidation, and
      color change were studied in wheat flour-based model systems during frying at
      160, 170, 180, and 190  degrees C up to 13 min and data were fitted to
      mathematical models. Additionally, an Arrhenius-type dependency with temperature
      was evaluated for all studied responses. More drastic frying conditions increased
      significantly (P <= 0.05) the furan content of fried samples. Furan formation
      followed a sigmoid trend with frying time only for frying temperature of 190 
      degrees C (RMS190 degrees C : 7.6%). At lower temperatures, furan generation did
      not reach the asymptotic concentration level. Color change, lipid oxidation, and
      oil absorption increased with frying temperature and followed asymptotic
      relationships with frying time. For all evaluated temperatures, color change
      (RMS: 4.4% to 12.5%) and polar compound generation (RMS: 2.6% to 7.4%) presented
      good fit to a first-order kinetic model. Oil absorption was successfully fit to a
      mass balance-based model (RMS: 10.0% to 19.8%). Under the experimental conditions
      studied, only color change (EA : 15.47 kJ/mol), lipid oxidation (EA : 6.67
      kJ/mol), and oil absorption (EA : 76.98 kJ/mol) presented good fit (RMS: 0.7% to
      6.3%) to an Arrhenius-type equation. Based on our results, the keeping of frying
      temperature below 180  degrees C and the reduction of the frying time would
      contribute to reduce not only the final furan occurrence in fried foods but also
      their oil content.

PMID- 27886378
TI  - Interactive Effect of Corticosterone and Lactate on Regulation of Testosterone
      Production in Rat Leydig Cells.
AB  - The increasing intensity of exercise enhanced corticosterone and lactate
      production in both humans and rodents. Our previous studies also demonstrated
      that lactate could stimulate testosterone production in vivo and in vitro.
      However, the production of testosterone in response to combined corticosterone
      and lactate on Leydig cells, and underlying molecular mechanisms are remained
      unclear. This study investigated the changes in testosterone levels of Leydig
      cells upon exposure to lactate, corticosterone or combination of both, and
      revealed the detailed mechanisms. Leydig cells were isolated from rat testes, and
      treated with different concentrations of lactate (2.5-20 mM), cortiosterone (10-9
      -10-4  M) and lactate plus corticosterone. The production of testosterone were
      assayed by radioimmunoassay, and the key molecular proteins, including
      luteinizing hormone receptor (LHR), protein kinase A (PKA), steroidogenic acute
      regulatory protein (StAR), and cholesterol P450 side-chain cleavage enzyme
      (P450scc) involved in testosterone production were performed by Western blot.
      Results showed that testosterone levels were significantly increased with
      lactate, while decresed with corticosterone and lactate plus corticosterone
      treatment. Protein expressions of LHR and P450scc were upregulated with lactate
      treatment. However, PKA and P450scc were downregulated by lactate plus
      corticosterone treatment. This downregulation was followed by decreased
      testoterone levels in Leydig cells. Furthermore, acetylated cAMP, which activates
      testosterone production was increased with lactate, but not altered by
      conrtiosterone. Our findings conclude that corticosterone may interfere with
      lactate, and restrict lactate-stimulated testosterone production in Leydig cells.
      J. Cell. Physiol. 232: 2135-2144, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27886379
TI  - Supernatants of Adipocytes From Obese Versus Normal Weight Women and Breast
      Cancer Cells: In Vitro Impact on Angiogenesis.
AB  - Breast cancer is correlated with a higher risk of metastasis in obese
      postmenopausal women. Adipokines, whose plasma concentrations are modulated in
      obese subjects and adipocytes surround mammary cells, suggesting that adipocyte
      secretome affect mammary tumorogenesis. We hypothesize that mature adipocyte
      secretions from obese women conditioned or not by breast neoplasic cells,
      increase changes on the angiogenesis stages. Supernatants of human mature
      adipocytes, differentiated from stem cells of either adipose tissue of normal
      weight (MA20) or obese (MA30) women or obtained from co-cultures between MA20 and
      MA30 and breast cancer cell line MCF-7, were collected. The impact of these
      supernatants was investigated on proliferation, migration, and tube formation by
      endothelial cells (HUVEC). MA20 and MA30 showed a preservation of their
      "metabolic memory" (increase of Leptin, ObR, VEGF, CYP19A1, and a decrease of
      Adiponectin expression in MA30 compared to MA20). Supernatants from obese
      adipocytes increased HUVEC proliferation, migration, and sprouting like with
      supernatants obtained from co-cultures of MA/MCF-7 regardless the women's BMI.
      Additional analyses such as the use of neutralizing antibodies, analysis of
      supernatants (Milliplex(r)) and variations in gene expression (qRT-PCR), strongly
      suggest an implication of IL-6, or a synergistic action among adipokines,
      probably associated with that of VEGF or IL-6. As a conclusion, supernatants from
      co-cultures of MA30 and MCF-7 cells increase proliferation, migration, and
      sprouting of HUVEC cells. These results provide insights into the interaction
      between adipocytes and epithelial cancer cells, particularly in case of obesity.
      The identification of synergistic action of adipokines would therefore be a great
      interest in developing preventive strategies. J. Cell. Physiol. 232: 1808-1816,
      2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27886380
TI  - Acceptability and Preference Drivers of Freshly Roasted Peanuts.
AB  - The objectives of this study were to determine and compare the sensory
      perceptions and aroma volatiles of 6 freshly roasted peanut samples and to
      explore the drivers of consumer acceptability. Normal-oleic Georgia 06G kernels
      (06G), high-oleic Georgia 13M kernels (13M), Georgia runner (mixed) in-shell
      (InR) & kernels (R), and Virginia (mixed) in-shell (InVA) & kernels (VA) were
      roasted to medium doneness for consumers, descriptive, and gas chromatography
      mass spectroscopy (GC-MS) tests. For Virginia variety, InVA was preferred over
      VA. High-oleic 13M was preferred over normal-oleic 06G in overall liking, aroma
      liking, flavor liking, sweet liking and roasted peanut flavor liking, and so on.
      Descriptive tests showed that 06G was highest in bitter taste. Cluster analysis
      divided consumers into 3 segments. Consumer overall liking was positively
      correlated with attributes related to fresh products and negatively correlated
      with the attributes that gave consumer the impression of oxidation and overroast.
      Consumer in cluster 3 had more light eaters and paid less attention to textural
      aspects. GC-MS data identified benzene derivatives and pyrazines as the principal
      volatiles. 06G had significantly (P <= 0.05) higher concentration of alcohols and
      aldehydes with the lowest concentration of pyrazines. As the major pyrazine, 2,5
      dimethyl-pyrazine had the strongest correlation with roasted peanutty flavor,
      while octanal, nonanal, hexanal, and 2-pentyl pyridine showed closer correlation
      with overall oxidized flavor.

PMID- 27886381
TI  - Composition-Based Prediction of Temperature-Dependent Thermophysical Food
      Properties: Reevaluating Component Groups and Prediction Models.
AB  - Prediction of temperature-dependent thermophysical properties (thermal
      conductivity, density, specific heat, and thermal diffusivity) is an important
      component of process design for food manufacturing. Current models for prediction
      of thermophysical properties of foods are based on the composition, specifically,
      fat, carbohydrate, protein, fiber, water, and ash contents, all of which change
      with temperature. The objectives of this investigation were to reevaluate and
      improve the prediction expressions for thermophysical properties. Previously
      published data were analyzed over the temperature range from 10 to 150  degrees
      C. These data were analyzed to create a series of relationships between the
      thermophysical properties and temperature for each food component, as well as to
      identify the dependence of the thermophysical properties on more specific
      structural properties of the fats, carbohydrates, and proteins. Results from this
      investigation revealed that the relationships between the thermophysical
      properties of the major constituents of foods and temperature can be
      statistically described by linear expressions, in contrast to the current
      polynomial models. Links between variability in thermophysical properties and
      structural properties were observed. Relationships for several thermophysical
      properties based on more specific constituents have been identified. Distinctions
      between simple sugars (fructose, glucose, and lactose) and complex carbohydrates
      (starch, pectin, and cellulose) have been proposed. The relationships between the
      thermophysical properties and proteins revealed a potential correlation with the
      molecular weight of the protein. The significance of relating variability in
      constituent thermophysical properties with structural properties--such as
      molecular mass--could significantly improve composition-based prediction models
      and, consequently, the effectiveness of process design.

PMID- 27886382
TI  - Evaluation of the Effects of Cucumis sativus Seed Extract on Serum Lipids in
      Adult Hyperlipidemic Patients: A Randomized Double-Blind Placebo-Controlled
      Clinical Trial.
AB  - Hyperlipidemia is associated with increased risk of atherosclerosis; therefore,
      control of this risk factor is very important in preventing atherosclerosis.
      Cucumber (Cucumis sativus) seed is used traditionally as a lipid-lowering
      nutritional supplement. The aim of this study was to evaluate the effect of
      cucumber seed extract on serum lipid profile in adult patients with mild
      hyperlipidemia. In a randomized double-blind placebo-controlled clinical trial,
      hyperlipidemic patients with inclusion criteria were randomly and equally
      assigned to either Cucumis or placebo groups and used one medicinal or placebo
      capsule, respectively, once daily with food for 6 wk. Body mass index (BMI) as
      well as fasting serum levels of total cholesterol, triglycerides (TG), low
      density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) were measured
      for all patients pre- and post-intervention and finally the changes were compared
      between the groups. Twenty-four patients in Cucumis group and 23 patients in
      placebo group completed the study. Cucumis seed extract resulted in significant
      reduction of total cholesterol (P = 0.016), LDL-C (P < 0.001), TG (P < 0.001),
      and BMI (P < 0.001) as well as significant increase of HDL-C (P = 0.012) compared
      to placebo. In conclusion, the consumption of C. sativus seed extract with daily
      dose of 500 mg results in desirable effects on serum lipid profile in adult
      hyperlipidemic patients. Therefore, cucumber seed could be considered as a food
      supplement for treatment of dyslipidemia.

PMID- 27886383
TI  - Permanent tooth loss and sugar-sweetened beverage intake in U.S. young adults.
AB  - OBJECTIVE: In young adults, sugar-sweetened beverage (SSB) intake is associated
      with dental caries, which in turn is a major contributor to tooth loss. The
      independent role of SSB intake on tooth loss, however, has not been well
      described. This cross-sectional study examined associations between tooth loss
      and SSB intake among U.S. young adults. METHODS: The outcome was number of
      permanent teeth lost because of dental caries or periodontal disease (0, 1-5, >=6
      teeth). Data from the 2012 Behavioral Risk Factor Surveillance System were used.
      The 22,526 adults aged 18-39 years completed the Sugar Drink Module. The exposure
      variable was daily frequency of SSB intake. We used multinomial logistic
      regression to examine the adjusted associations between tooth loss and daily SSB
      consumption (0, >0 to <1, 1-2, >2 times/day). RESULTS: Approximately, 26% of
      young adults reported losing at least one permanent tooth. Tooth loss was
      positively associated with SSB intake frequency; the odds of losing 1-5 teeth
      were higher among adults drinking SSBs >0-<1 times/day (OR = 1.44, 95%CI = 1.16
      1.79), 1-2 times/day (OR = 1.58, 95%CI = 1.25-1.99), and >2 times/day (OR = 1.97,
      95%CI = 1.51-2.58) than non-SSB consumers. The odds of losing >=6 teeth were
      higher among adults drinking SSBs 1-2 times/day (OR = 2.20, 95%CI = 1.15-4.22)
      and >2 times/day (OR = 2.81, 95%CI = 1.37-5.76) than non-SSB consumers.
      CONCLUSIONS: Frequency of SSB consumption was positively associated with tooth
      loss among young adults even when the average SSB intake was less than one time
      per day. This study suggests that efforts to reduce SSB intake among young adults
      may help to decrease the risk of tooth loss.

PMID- 27886384
TI  - Valorization of functional properties of extract and powder of olive leaves in
      raw and cooked minced beef meat.
AB  - BACKGROUND: Olive leaves (OL), available in huge amounts from pruning, are known
      to be a useful source of biologically active compounds. This study investigated
      the potential application of OL as a supplement to minced beef meat in order to
      develop a functional product. The effect of OL extract or powder (100 and 150 ug
      phenols g-1 meat) on the quality and stability of raw and cooked meat during
      refrigerated storage was examined. RESULTS: Microwave drying at 600 W gave OL
      with the highest antioxidant quality (evaluated by TEAC/[phenols] (mg mg-1 ) and
      DPPH/[phenols] (mg mg-1 )) compared with other methods. OL showed an ability to
      inhibit (P < 0.05) lipid oxidation (TBARS values (mg MDA kg-1 ) were reduced by
      25-65%) and myoglobin oxidation (metmyoglobin production was 43-65% in control
      samples and 14-35% in treated samples). OL also improved the technological
      quality of the meat, decreasing (P < 0.05) storage loss (%) and defrosting loss
      (%) without affecting cooking loss (%) and Napole yield (%). Sensory properties
      were not modified by the added ingredient at the tested levels (P < 0.05).
      CONCLUSION: OL (extract or powder) may have applications in the development of
      functional meat products of good technological quality that remain stable during
      storage. (c) 2016 Society of Chemical Industry.

PMID- 27886386
TI  - Costs of perennial allergic rhinitis and allergic asthma increase with severity
      and poor disease control.
AB  - BACKGROUND: Perennial allergic rhinitis (PAR) represents a global and public
      health problem, due to its prevalence, morbidity, and impact on the quality of
      life. PAR is frequently associated with allergic asthma (AA). Costs of PAR with
      or without AA are poorly documented. OBJECTIVE: Our study aimed to detail medical
      resource utilization (MRU) and related direct cost for PAR, with or without
      concomitant AA, in France. METHODS: Using Electronic Health Records (EHRs), we
      identified in 2010 two cohorts of PAR patients, based on General Practitioners'
      diagnoses and prescribing data, with and without concomitant AA. For each
      patient, the EHRs were linked to corresponding claims data with MRU and costs
      during years 2011 to 2013. Predefined subgroup analyses were performed according
      to severity of PAR and level of AA control. RESULTS: The median annual cost
      reimbursed by social security system for a patient with PAR, and no AA was 159?
      in 2013. This varied from 111? to 188? depending on PAR severity. For patients
      with PAR and concomitant AA, the median annual cost varied between 266? and 375?,
      and drug treatment accounted for 42-55% of the costs, depending on asthma
      control. CONCLUSION: This study linking diagnoses from EHRs to claims data
      collected valid information on PAR management, with or without concomitant AA,
      and on related costs. There was a clear increase in costs with severity of PAR
      and control of AA.

PMID- 27886387
TI  - Coping strategies, alexithymia and anxiety in young patients with food allergy.
AB  - BACKGROUND: Food allergy is major public health concern affecting nearly 15
      million Americans and 80 million Europeans. Risk of anaphylaxis and implications
      for social activities affect patients' quality of life and psychological well
      being. We previously found that young patients reported higher levels of
      alexithymia (difficulty in recognizing and expressing emotions) compared with
      healthy peers and may influence affect, management style and clinical outcomes.
      This study aimed to explore links between coping strategies, alexithymia and
      anxiety among food-allergic adolescents and young adults. METHODS: Ninety-two
      patients with IgE-mediated food allergy (mean age 18.6 years) completed Coping
      Orientation to Problems Experienced Inventory, Toronto Alexithymia Scale and
      Trait Anxiety subscale of State-Trait Anxiety Inventory. Multivariate analyses of
      variance assessed differences and associations between subgroups on the scales.
      RESULTS: Significant differences found between alexithymia levels in coping style
      were explained by Avoidance strategies. 'Avoidance' had the highest contribution
      in explaining alexithymia, followed by trait anxiety, age, anaphylaxis and social
      support. Respondents with higher alexithymia use avoidance as coping strategy
      over and above other coping strategies such as problem-solving and positive
      thinking, are younger, will have experienced anaphylaxis and will have lower
      social support. CONCLUSIONS: Recognizing the specific role of affect regulation
      in health behaviours may constitute an important step in supporting patients to
      explore more adaptive strategies.

PMID- 27886385
TI  - Nonreciprocal complementation of KNOX gene function in land plants.
AB  - Class I KNOTTED-LIKE HOMEOBOX (KNOX) proteins regulate development of the
      multicellular diploid sporophyte in both mosses and flowering plants; however,
      the morphological context in which they function differs. In order to determine
      how Class I KNOX function was modified as land plants evolved, phylogenetic
      analyses and cross-species complementation assays were performed. Our data reveal
      that a duplication within the charophyte sister group to land plants led to
      distinct Class I and Class II KNOX gene families. Subsequently, Class I sequences
      diverged substantially in the nonvascular bryophyte groups (liverworts, mosses
      and hornworts), with moss sequences being most similar to those in vascular
      plants. Despite this similarity, moss mutants were not complemented by vascular
      plant KNOX genes. Conversely, the Arabidopsis brevipedicellus (bp-9) mutant was
      complemented by the PpMKN2 gene from the moss Physcomitrella patens. Lycophyte
      KNOX genes also complemented bp-9 whereas fern genes only partially complemented
      the mutant. This lycophyte/fern distinction is mirrored in the phylogeny of KNOX
      interacting BELL proteins, in that a gene duplication occurred after divergence
      of the two groups. Together, our results imply that the moss MKN2 protein can
      function in a broader developmental context than vascular plant KNOX proteins,
      the narrower scope having evolved progressively as lycophytes, ferns and
      flowering plants diverged.

PMID- 27886389
TI  - Meaningful coping with chronic pain: Exploring the interplay between goal
      violation, meaningful coping strategies and life satisfaction in chronic pain
      patients.
AB  - Trying to cope with chronic pain is a highly demanding and challenging task and
      pain patients often need to reformulate goals or aspirations due to their pain
      condition. This goal violation is often related with experienced distress and
      requires coping processes in order to decrease the distress and stimulate a
      healthy adaptation. Some scholars, however, argued that in so-called unsolvable
      or irreparable stressors such as chronic pain, conventional coping strategies
      like problem-focused coping might not be the most adaptive option. In these
      situations, meaningful coping strategies attempting to transform the meaning of
      the stressful experience would be more accurate. In this study, we aim to test if
      goal violation triggers meaningful coping strategies over time and whether
      engagement in these meaningful coping strategies result in improved life
      satisfaction, as an indicator of adaptation. A longitudinal three wave study in a
      sample of paint patients (n = 125) tests whether goal violation triggers positive
      reappraisal and downward comparison, two possible meaningful coping strategies.
      The study furthermore tests if engagement in these strategies results in a better
      adaptation to the pain condition, reflected in higher life satisfaction. Results
      partially supported our hypotheses by pointing to the benevolent role of downward
      comparison on life satisfaction via decreased goal violation of pain patients.
      Our findings however did also show that positive reappraisal predicted lower life
      satisfaction via increased levels of appraised goal violation which questions the
      role of positive reappraisal as a genuine meaningful coping strategy.
      Implications and limitations are discussed.

PMID- 27886388
TI  - Phytate/calcium molar ratio does not predict accessibility of calcium in ready-to
      eat dishes.
AB  - BACKGROUND: Phytic acid (PA), a naturally occurring compound of plant food, is
      generally considered to affect mineral bioavailability. The aim of this study was
      to investigate the reliability of the PA/calcium molar ratio as a predictive
      factor of calcium accessibility in composed dishes and their ingredients.
      RESULTS: Dishes were chosen whose ingredients were rich in Ca (milk or cheese) or
      in PA (whole-wheat cereals) in order to consider a range of PA/Ca ratios (from 0
      to 2.4) and measure Ca solubility using an in vitro approach. The amounts of
      soluble Ca in composed dishes were consistent with the sum of soluble Ca from
      ingredients (three out of five meals) or higher. Among whole-wheat products,
      bread showed higher Ca accessibility (71%, PA/Ca = 1.1) than biscuits (23%, PA/Ca
      = 0.9) and pasta (15%, PA/Ca = 1.5), and among Ca-rich ingredients, semi-skimmed
      milk displayed higher Ca accessibility (64%) than sliced cheese (50%) and
      Parmesan (38%). No significant correlation between the PA/Ca ratio and Ca
      accessibility was found (P = 0.077). CONCLUSION: The reliability of the PA/Ca
      ratio for predicting the availability of calcium in composed dishes is
      unsatisfactory; data emphasized the importance of the overall food matrix
      influence on mineral accessibility. (c) 2016 Society of Chemical Industry.

PMID- 27886390
TI  - Green, Yellow, and Red risk perception in everyday life - a communication tool.
AB  - BACKGROUND: Adolescents have the highest risk for food allergy-related
      fatalities. Our main aim was to investigate the level of risk in everyday social
      situations as perceived by adolescents/young adults with peanut allergy, their
      families, and their friends. METHODS: The web-based 'Colours Of Risks' (COR)
      questionnaire was completed by 70 patients (aged 12-23 years), 103 mothers and
      fathers, 31 siblings (aged 12-26 years), and 42 friends (aged 12-24 years). COR
      deals with six main contexts (home, school/university, work, visiting/social
      activities, special occasions/parties, and vacations), each with 1-12 items.
      Response categories are green (I feel safe), yellow (I feel uncertain), or red (I
      feel everything is risky). RESULTS: There was a high level of agreement between
      participants in defining situations as safe, uncertain, or risky, but female
      patients and mothers rated fewer situations as safe compared to male patients and
      fathers. Being with close friends and family, and attending planned parties
      without alcohol were perceived as situations of low risk. While 94% of patients
      took an epinephrine auto-injector (EAI) into risky situations, only 65% took it
      into safe situations. In contrast to the close family, 31% of the friends did not
      know the patient had an EAI, and fewer knew how to administer the EAI.
      CONCLUSION: Young adults with peanut allergy face challenges when moving from the
      safe home with ready assistance if needed, to independence with unpredictable
      surroundings and less certain help. Perceived 'safe' situations may in fact be
      the riskiest, as patients often do not take the EAI with them.

PMID- 27886392
TI  - Deregulated expression of EZH2 in congenital brainstem disconnection.

PMID- 27886391
TI  - Estimate of the total costs of allergic rhinitis in specialized care based on
      real-world data: the FERIN Study.
AB  - BACKGROUND: Despite the socioeconomic importance of allergic rhinitis (AR), very
      few prospective studies have been performed under conditions of clinical practice
      and with a sufficiently long observation period outside the clinical trial
      scenario. We prospectively estimated the direct and indirect costs of AR in
      patients attending specialized clinics in Spain. METHODS: Patients were recruited
      at random from allergy outpatient clinics in 101 health centers throughout Spain
      over 12 months. We performed a multicenter, observational, prospective study
      under conditions of clinical practice. We analyzed direct costs from a funder
      perspective (healthcare costs) and from a societal perspective (healthcare and
      non-healthcare costs). Indirect costs (absenteeism and presenteeism [productivity
      lost in the workplace]) were also calculated. The cost of treating conjunctivitis
      was evaluated alongside that of AR. RESULTS: The total mean cost of AR per
      patient-year (n = 498) was ?2326.70 (direct, ?553.80; indirect, ?1772.90). Direct
      costs were significantly higher in women (?600.34 vs ?484.46, P = 0.02). Total
      costs for intermittent AR were significantly lower than for persistent AR
      (?1484.98 vs ?2655.86, P < 0.001). Total indirect costs reached ?1772.90
      (presenteeism, ?1682.71; absenteeism, ?90.19). The direct costs of AR in patients
      with intermittent asthma (?507.35) were lower than in patients with mild
      persistent asthma (?719.07) and moderate-persistent asthma (?798.71) (P = 0.006).
      CONCLUSIONS: The total cost of AR for society is considerable. Greater frequency
      of symptoms and more severe AR are associated with higher costs. Indirect costs
      are almost threefold direct costs, especially in presenteeism. A reduction in
      presenteeism would generate considerable savings for society.

PMID- 27886393
TI  - Blinded versus unblinded estimation of a correlation coefficient to inform
      interim design adaptations.
AB  - Regulatory authorities require that the sample size of a confirmatory trial is
      calculated prior to the start of the trial. However, the sample size quite often
      depends on parameters that might not be known in advance of the study.
      Misspecification of these parameters can lead to under- or overestimation of the
      sample size. Both situations are unfavourable as the first one decreases the
      power and the latter one leads to a waste of resources. Hence, designs have been
      suggested that allow a re-assessment of the sample size in an ongoing trial.
      These methods usually focus on estimating the variance. However, for some methods
      the performance depends not only on the variance but also on the correlation
      between measurements. We develop and compare different methods for blinded
      estimation of the correlation coefficient that are less likely to introduce
      operational bias when the blinding is maintained. Their performance with respect
      to bias and standard error is compared to the unblinded estimator. We simulated
      two different settings: one assuming that all group means are the same and one
      assuming that different groups have different means. Simulation results show that
      the naive (one-sample) estimator is only slightly biased and has a standard error
      comparable to that of the unblinded estimator. However, if the group means
      differ, other estimators have better performance depending on the sample size per
      group and the number of groups.

PMID- 27886394
TI  - Differences in the Evaluation of Generic Statements About Human and Non-Human
      Categories.
AB  - Generic statements (e.g., "Birds lay eggs") express generalizations about
      categories. Current theories suggest that people should be especially inclined to
      accept generics that involve threatening information. However, previous tests of
      this claim have focused on generics about non-human categories, which raises the
      question of whether this effect applies as readily to human categories. In
      Experiment 1, adults were more likely to accept generics involving a threatening
      (vs. a non-threatening) property for artifacts, but this negativity bias did not
      also apply to human categories. Experiment 2 examined an alternative hypothesis
      for this result, and Experiments 3 and 4 served as conceptual replications of the
      first experiment. Experiment 5 found that even preschoolers apply generics
      differently for humans and artifacts. Finally, Experiment 6 showed that these
      effects reflect differences between human and non-human categories more
      generally, as adults showed a negativity bias for categories of non-human
      animals, but not for categories of humans. These findings suggest the presence of
      important, early-emerging domain differences in people's judgments about
      generics.

PMID- 27886395
TI  - Popdc1/Bves Functions in the Preservation of Cardiomyocyte Viability While
      Affecting Rac1 Activity and Bnip3 Expression.
AB  - The Popeye domain containing1, also called Bves (Popdc1/Bves), is a transmembrane
      protein that functions in muscle regeneration, heart rate regulation, hypoxia
      tolerance, and ischemia preconditioning. The expression of Popdc1/Bves is
      elevated in cardiomyocytes maintained in serum free defined medium. We
      hypothesized that Popdc1/Bves is important for cardiomyocyte survival under the
      stress of serum deprivation and investigated the mechanisms involved. A deficit
      in Popdc1/Bves, achieved by siRNA-mediated gene silencing, results in
      cardiomyocyte injury and death, upregulation of the pro-apoptotic protein Bcl
      2/adenovirus E1B 19-kDa interacting protein3 (Bnip3), as well as reduction in
      Rac1-GTPase activity and in Akt phosphorylation. Combined Popdc1/Bves and Bnip3
      silencing attenuated cell injury and prevented Bnip3 upregulation induced by the
      silencing of Popdc1/Bves alone. Chromatin immunoprecipitation indicated an
      increased binding of the transcription factor FoxO3 to the Bnip3 promoter
      although augmentation of FoxO3 in the nuclei was not detected. By contrast, the
      transcription factor NFkappaB was excluded from the nuclei of Popdc1/Bves
      deficient cardiomyocytes and exhibited decreased binding to the Bnip3 promoter.
      The data indicates that Popdc1/Bves plays a role in the preservation of
      cardiomyocyte viability under serum deficiency through the alteration of Rac1
      activity and the regulation of Bnip3 expression by FoxO3 and NFkappaB
      transcription factors pointing to Popdc1/Bves as a potential target to enhance
      heart protection. J. Cell. Biochem. 118: 1505-1517, 2017. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27886396
TI  - 5-ALA-mediated photodynamic therapy reduces the parasite load in mice infected
      with Leishmania braziliensis.
AB  - Photodynamic therapy (PDT) has proven to be an effective alternative for the
      treatment of cutaneous leishmaniasis. Skin lesions consist of ulcers with well
      defined raised edges, and granular floor. Th1 immune response is the protective
      profile in patients infected with Leishmania. In this study, the photodynamic
      therapy with 5-aminolevulinic acid, the parasitic load, and the modulation of the
      immune response was evaluated in mice infected with Leishmania braziliensis.
      Balb/c mice were infected with L. braziliensis and subsequently treated with
      three sections of PDT. The parasite load and mRNA expression of cytokines (IFN
      gamma, IL-4, IL-17, IL-22, IL-27, IL-10) and transcription factors (GATA-3, Foxp3
      and T-bet) were analysed by quantitative PCR. The parasite load in the treated
      group was significantly lower than in the untreated group (P<.0001); in PDT
      treated animals, we observed an increase in IFN-gamma and T-bet mRNA (P=.012 and
      P=.0071). There was a significant reduction in mRNA expression of IL-22
      associated with an increased expression of IL-27 mRNA in the animals treated with
      light only (P=.0001). 5-ALA associated with photodynamic therapy promotes a
      reduction in parasite load and an increased expression of IFN-gamma and T-bet
      mRNA.

PMID- 27886398
TI  - An in situ toxicity identification and evaluation water analysis system:
      Laboratory validation.
AB  - It is difficult to assess the toxicity of a single stressor and establish a
      strong stressor-causality link when multiple stressors coexist. Toxicity
      identification evaluation (TIE) methodology uses a series of chemical and
      physical manipulations to fractionate compounds within a matrix and
      systematically identify potential toxicants. The current US Environmental
      Protection Agency application of TIE can provide valuable information but often
      lacks ecological realism and is subject to laboratory-related artifacts. An in
      situ TIE device (iTIED) was designed to assess the sources of toxicity in aquatic
      ecosystems. For this laboratory validation, each unit was equipped with a sorbent
      resin chamber, an organism exposure chamber, a water collection container, and a
      peristaltic pump. Chemical analyses of water processed by each iTIED unit were
      compared with both lethal and sublethal molecular responses of the organisms. The
      compound removal effectiveness of different sorbent resins was also compared. In
      addition to successfully fractionating diverse chemical mixtures, the iTIED
      demonstrated a potential for early detection of molecular biomarkers, which could
      identify chronic toxicity that may go unnoticed in traditional TIE assays.
      Utilizing this novel in situ system will reduce the uncertainty associated with
      laboratory-based simulations and aid management efforts in targeting compounds
      that pose the greatest threat. Environ Toxicol Chem 2017;36:1636-1643. (c) 2016
      SETAC.

PMID- 27886397
TI  - Telomerase and N-Cadherin Differential Importance in Adrenocortical Cancers and
      Adenomas.
AB  - Adrenocortical carcinomas (ACC) are most frequently highly aggressive tumors. We
      assessed the telomerase reverse transcriptase (TERT) and N-cadherin role in the
      biology of ACC and their potential utility as molecular biomarkers, in different
      types of tumoral adrenocortical tissue. A total of 48 adrenal cortex samples (39
      tumoral and 9 normal adrenal glands) were studied. TERT promoter mutations were
      searched by PCR and Sanger sequencing in two hotspots positions (-124 and -146).
      Also, telomerase and N-cadherin expression were evaluated by
      immunohistochemistry. TERT promoter mutations were not detected in any of the
      samples either malignant or benign. Telomerase nuclear expression was present in
      26.6% of ACC and in 45.5% of non-functioning adenomas. It was absent in benign
      Cushing's lesions and in normal adrenal glands. Contrarily, N-cadherin was always
      expressed in the cellular membranes of benign adenomas or normal adrenals but no
      expression was detected in the majority of ACC. Nuclear telomerase and membrane N
      cadherin expression were positively correlated in ACCs. We conclude that in ACC,
      the loss of N-cadherin is a frequent phenomenon while the existence of TERT
      promoter mutations is not and nuclear telomerase expression is present in only a
      minority of cases. Since the loss of N-cadherin expression was identified in both
      high and low proliferative ACC, this marker should be considered important for
      diagnostic application. Our study also suggests the existence of a TERT non
      canonical function in cell adhesion. J. Cell. Biochem. 118: 2064-2071, 2017. (c)
      2017 Wiley Periodicals, Inc.

PMID- 27886399
TI  - Simulation of total knee arthroplasty in 5 degrees  or 7 degrees  valgus: A study
      of gap imbalances and changes in limb and knee alignments from native.
AB  - This study calculated the frequency of occurrence of gap imbalances between
      medial and lateral compartments at 0 degrees  flexion and within a compartment
      between 0 degrees  and 90 degrees  flexion, and changes in limb and knee
      alignment from native after computer simulation of total knee arthroplasty (TKA)
      with the knee set in 5 degrees  or 7 degrees  valgus at 0 degrees  flexion. TKA
      was simulated on 49 3D bone models of native limbs. At 0 degrees  flexion, the
      femoral component was set in 5 degrees  or 7 degrees  valgus from the anatomic
      axis of the femur, and the tibial component was set 0 degrees  to the tibial
      anatomic axis. At 90 degrees  flexion, internal-external rotation of the femoral
      component was set perpendicular to the anteroposterior axis of the trochlear
      groove (Method 1), parallel to the transepicondylar axis (Method 2), 3 degrees 
      externally rotated to the posterior condylar axis (Method 3), and gap-balanced to
      the tibial resection at 0 degrees  flexion (Method 4). For 5 degrees  and 7
      degrees  valgus knees, the frequency of occurrence of TKAs (1) with >=2 mm gap
      imbalance between compartments at 0 degrees  flexion was >=49%, (2) with  >=2 mm
      gap imbalance within a compartment between 0 degrees  and 90 degrees  flexion
      ranged from 43-69% for Methods 1, 2, and 3, and (3) with >=2 degrees  change in
      limb and knee alignment from native was >=47%. Achieving balanced gaps between
      compartments at 0 degrees  flexion may often require soft tissue release.
      Unbalanced gaps within a compartment between 0 degrees  and 90 degrees  flexion
      represent a potential instability which is difficult to surgically correct. (c)
      2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 35:2031-2039, 2017.

PMID- 27886400
TI  - Review of the aetiology, diagnostics and outcomes of childhood encephalitis from
      1970 to 2009.
AB  - AIM: Encephalitis is a rare, serious condition, and antiviral therapies,
      increased knowledge of inflammatory pathways and improved diagnostics have
      increased the therapeutic possibilities. We describe 40 years of childhood
      encephalitis in Sweden, covering the diagnostics, aetiology and outcomes.
      METHODS: We reviewed the clinical data that were available for all children
      discharged from the Karolinska University Hospital in Stockholm following
      treatment for encephalitis from 1970 to 2009. The hospital treated all children
      in the region with the condition during the study period. RESULTS: There were 408
      episodes of encephalitis from 1970 to 2009 and the incidence was similar over the
      whole period, ranging from 6.4 to 8.7 per 100 000 child years. Although mortality
      markedly decreased from 10% in the first decade to zero in the last decade, and
      aetiologies shifted, no clear long-term improvements in outcome were seen. The
      need for intensive care was unchanged (18-20%) for each of the study intervals,
      possibly indicating that the severity of cases remained unaltered. CONCLUSION:
      Understanding the pathophysiological mechanisms of encephalitis is vitally
      important for developing more efficient treatment regimens. As well as reporting
      the results of this 40-year study, this study considers possible explanations,
      addresses current therapeutic options and explores directions for central nervous
      system infection research.

PMID- 27886401
TI  - Not all that glitters is gold-Electron microscopy study on uptake of gold
      nanoparticles in Daphnia magna and related artifacts.
AB  - Increasing use of engineered nanoparticles has led to extensive research into
      their potential hazards to the environment and human health. Cellular uptake from
      the gut is sparsely investigated, and microscopy techniques applied for uptake
      studies can result in misinterpretations. Various microscopy techniques were used
      to investigate internalization of 10-nm gold nanoparticles in Daphnia magna gut
      lumen and gut epithelial cells following 24-h exposure and outline potential
      artifacts (i.e., high-contrast precipitates from sample preparation related to
      these techniques). Light sheet microscopy confirmed accumulation of gold
      nanoparticles in the gut lumen. Scanning transmission electron microscopy and
      elemental analysis revealed gold nanoparticles attached to the microvilli of gut
      cells. Interestingly, the peritrophic membrane appeared to act as a semipermeable
      barrier between the lumen and the gut epithelium, permitting only single
      particles through. Structures resembling nanoparticles were also observed inside
      gut cells. Elemental analysis could not verify these to be gold, and they were
      likely artifacts from the preparation, such as osmium and iron. Importantly, gold
      nanoparticles were found inside holocrine cells with disrupted membranes. Thus,
      false-positive observations of nanoparticle internalization may result from
      either preparation artifacts or mistaking disrupted cells for intact cells. These
      findings emphasize the importance of cell integrity and combining elemental
      analysis with the localization of internalized nanoparticles using transmission
      electron microscopy. Environ Toxicol Chem 2017;36:1503-1509. (c) 2016 SETAC.

PMID- 27886402
TI  - Analysis of Paracoccidioides lutzii mitochondria: a proteomic approach.
AB  - The genus Paracoccidioides is composed of thermal dimorphic fungi, causative
      agents of paracoccidioidomycosis, one of the most frequent systemic mycoses in
      Latin America. Mitochondria have sophisticated machinery for ATP production,
      which involves metabolic pathways such as citric acid and glyoxylate cycles,
      electron transport chain and oxidative phosphorylation. In addition, this
      organelle performs a variety of functions in the cell, working as an exceptional
      metabolic signalling centre that contributes to cellular stress responses, as
      autophagy and apoptosis in eukaryotic organisms. The aim of this work was to
      perform a descriptive proteomic analysis of mitochondria in Paracoccidioides
      lutzii yeast cells. After mitochondria fractionation, samples enriched in
      mitochondrial proteins were digested with trypsin and analysed using a NanoUPLC
      MSE system (Waters Corporation, Manchester, UK). Ours results revealed that the
      established protocol for purification of mitochondria was very effective for P.
      lutzii, and 298 proteins were identified as primarily mitochondrial, in our
      analysis. To our knowledge, this is the first compilation of mitochondrial
      proteins from P. lutzii, to date. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27886404
TI  - Adipophilin expression in cutaneous malignant melanoma.
AB  - BACKGROUND: The lipogenic pathway is upregulated in cancer cells, including
      melanomas. However, the pathological significance of cellular lipids in
      melanocytic lesions has yet to be determined. In this study, we evaluated
      intracytoplasmic lipid droplets in melanocytic nevi (MNs) and malignant melanomas
      via immunohistochemical analysis of adipophilin (ADP), which coats lipid
      droplets. METHODS: One hundred primary cutaneous melanocytic lesions [33 MNs, 17
      melanomas in situ (MIS), and 50 invasive melanomas (IMs)] were immunostained for
      ADP. The intensity score (IS) and proportion score (PS) of ADP staining in each
      case was recorded semiquantitatively on a scale of 0 to 3+. RESULTS: High ADP
      expression (IS2/3+ and PS2/3+) was observed in 27 primary cutaneous melanocytic
      lesions that consisted of 23 IMs, three MISs, and one MN. Consequently, high ADP
      expression was associated with malignancy (38.8% vs. 3.0%; p < 0.0001). Among the
      IMs, high ADP expression was more prevalent in pT3/4 than pT1/2 (63.3% vs. 23.8%;
      p = 0.01) and Stage 3/4 than Stage 1/2 (76.9% vs. 36.8%; p = 0.02). CONCLUSIONS:
      The majority of the melanocytic lesions with high ADP expression were malignant
      melanomas in our cohort. Therefore, ADP expression may serve as a sensitive
      diagnostic marker for malignant melanoma.

PMID- 27886405
TI  - Hypercalcemia in Necrobiotic Xanthogranuloma: First Reported Case and Insight
      Into Treatment.
AB  - Necrobiotic xanthogranuloma (NXG) is a rare systemic and progressive
      granulomatous disease first described in 1980. Given no established first-line
      therapy, treatment focuses on the control of skin lesions and associated
      complications. Despite it being a granulomatous disease, NXG has not been
      associated with hypercalcemia. About 140 cases of NXG have been reported to date
      but, to our knowledge, this is the first case to be complicated by hypercalcemia.
      Our case confirms a granulomatous disease-mediated production of 1alpha
      hydroxylase leading to increased synthesis of 1,25-dihydroxyvitamin D and
      subsequent hypercalcemia. Based on this pathophysiology, we elected to start
      systemic glucocorticoids, titrated to clinical and metabolic response. Steroid
      sparing agents need to be considered to avoid long-term complications but
      continue controlling this granulomatous disease. (c) 2017 American Society for
      Bone and Mineral Research.

PMID- 27886403
TI  - Rapid test for lung maturity, based on spectroscopy of gastric aspirate,
      predicted respiratory distress syndrome with high sensitivity.
AB  - AIM: Respiratory distress syndrome (RDS) is a major cause of mortality and
      morbidity in premature infants. By the time symptoms appear, it may already be
      too late to prevent a severe course, with bronchopulmonary dysplasia or
      mortality. We aimed to develop a rapid test of lung maturity for targeting
      surfactant supplementation. METHODS: Concentrations of the most surface-active
      lung phospholipid dipalmitoylphosphatidylcholine and sphingomyelin in gastric
      aspirates from premature infants were measured by mass spectrometry and expressed
      as the lecithin/sphingomyelin ratio (L/S). The same aspirates were analysed with
      mid-infrared spectroscopy. Subsequently, L/S was measured in gastric aspirates
      and oropharyngeal secretions from another group of premature infants using
      spectroscopy and the results were compared with RDS development. The 10-minute
      analysis required 10 MUL of aspirate. RESULTS: An L/S algorithm was developed
      based on 89 aspirates. Subsequently, gastric aspirates were sampled in 136
      infants of 24-31 weeks of gestation and 61 (45%) developed RDS. The cut-off value
      of L/S was 2.2, sensitivity was 92%, and specificity was 73%. In 59 cases, the
      oropharyngeal secretions had less valid L/S than gastric aspirate results.
      CONCLUSION: Our rapid test for lung maturity, based on spectroscopy of gastric
      aspirate, predicted RDS with high sensitivity.

PMID- 27886406
TI  - Disrupted pancreatic duct treated with a combination of endoscopic
      cystoduodenostomy and pancreatic duct fistualization through a pseudocyst wall
      using a lumen-apposing metal stent.
AB  - Management of disconnected pancreatic duct syndrome is complex and is
      increasingly approached using emerging endoscopic techniques. Herein, we present
      a case of recurrent pancreatitis in an elderly woman complicated by pseudocyst
      formation and complete pancreatic duct disruption. Her condition was treated with
      a novel combination of transpapillary stenting and cystduodenostomy in which a
      pancreatic duct stent was placed into an opening in the pseudocyst wall through a
      lumen-apposing metal stent. This allowed for effective drainage into the
      gastrointestinal tract and resolution of duct disruption. Post-procedure, the
      patient has had recovery of nutritional status and no further recurrence of
      pancreatic fluid collection. Endoscopic approaches to complete pancreatic duct
      disruption represent a viable and less invasive alternative to surgical
      management in selected cases.

PMID- 27886410
TI  - High-Electron-Mobility and Air-Stable 2D Layered PtSe2 FETs.
AB  - The electrical and optical measurements, in combination with density functional
      theory calculations, show distinct layer-dependent semiconductor-to-semimetal
      evolution of 2D layered PtSe2 . The high room-temperature electron mobility and
      near-infrared photo-response, together with much better air-stability, make PtSe2
      a versatile electronic 2D layered material.

PMID- 27886407
TI  - First-in-human assessment of PRX002, an anti-alpha-synuclein monoclonal antibody,
      in healthy volunteers.
AB  - BACKGROUND: alpha-Synuclein is a major component of pathologic inclusions that
      characterize Parkinson's disease. PRX002 is an antibody that targets alpha
      synuclein, and its murine parent antibody 9E4 has been shown in preclinical
      studies to reduce alpha-synuclein pathology and to protect against cognitive and
      motor deteriorations and progressive neurodegeneration in human alpha-synuclein
      transgenic mice. METHODS: This first-in-human, randomized, double-blind, placebo
      controlled, phase 1 study assessed the impact of PRX002 administered to 40
      healthy participants in 5 ascending-dose cohorts (n = 8/cohort) in which
      participants were randomly assigned to receive a single intravenous infusion of
      study drug (0.3, 1, 3, 10, or 30 mg/kg; n = 6/cohort) or placebo (n = 2/cohort).
      RESULTS: PRX002 demonstrated favorable safety, tolerability, and pharmacokinetic
      profiles at all doses tested, with no immunogenicity. No serious adverse events,
      discontinuations as a result of adverse events, or dose-limiting toxicities were
      reported. Serum PRX002 exposure was dose proportional; the average terminal half
      life across all doses was 18.2 days. A significant dose-dependent reduction in
      free serum alpha-synuclein (unbound to PRX002) was apparent within 1 hour after
      PRX002 administration, whereas total alpha-synuclein (free plus bound) increased
      dose-dependently, presumably because of the expected change in kinetics following
      antibody binding. CONCLUSIONS: This study demonstrates that serum alpha-synuclein
      can be safely modulated in a dose-dependent manner after single intravenous
      infusions of an anti-alpha-synuclein antibody. These findings support continued
      development of PRX002, including further characterization of its safety,
      tolerability, pharmacokinetics, and pharmacodynamic effects in the central
      nervous system in patients with Parkinson's disease. (c) 2016 The Authors.
      Movement Disorders published by Wiley Periodicals, Inc. on behalf of
      International Parkinson and Movement Disorder Society.

PMID- 27886412
TI  - Cowden Syndrome: Serendipitous Diagnosis in Patients with Significant Breast
      Disease. Case Series and Literature Review.
AB  - Cowden syndrome (CS) is a multi-system disease that carries an increased lifetime
      risk of developing certain cancers as well as benign neoplasms. The presence of
      features of CS in the general unaffected population results in difficulties in
      the recognition and diagnosis of this condition. Early diagnosis is essential to
      prevent the development of malignant neoplasms, yet despite the introduction of
      diagnostic criteria and risk calculators, accurate diagnosis remains a challenge.
      We identified three patients who presented to the symptomatic breast unit of a
      University Teaching Hospital over a period of 12 weeks who subsequently were
      diagnosed with CS. In this article, we discuss their clinical presentations as
      well as their path to diagnosis. The short timeframe between the presentations of
      these patients undoubtedly expedited their diagnosis. Upon application of
      internationally recognized diagnostic criteria, only two out of our three
      patients were accurately diagnosed. The risk of breast cancer in CS is comparable
      with that found in Hereditary Breast and Ovarian Cancer Syndrome and while a
      protocol for breast screening in these patients exists in most centres, no such
      protocol exists for patients with CS in our institution. The recommended cancer
      surveillance programs for patients with CS have not been found to prolong
      survival, however. CS consists of a vast array of diseases that span the various
      specialties and the subsequent varied phenotypic presentation poses diagnostic
      difficulties for clinicians as emphasized in our series. Continued research is
      required to improve recognition and diagnosis and will hopefully result in the
      emergence of life prolonging strategies.

PMID- 27886411
TI  - Dog ownership and physical activity among breast, prostate, and colorectal cancer
      survivors.
AB  - BACKGROUND: Dog ownership has been associated with higher rates of physical
      activity (PA) in several populations but no study to date has focused on cancer
      survivors. The purpose of this study was to examine the associations between dog
      ownership and PA among cancer survivors and to examine correlates of dog
      ownership. METHODS: A stratified random sample of 2062 breast cancer survivors,
      prostate cancer survivors, and colorectal cancer survivors was mailed a
      questionnaire assessing PA, social cognitive, dog ownership, demographic, and
      medical variables. RESULTS: Overall, 25% of the sample was dog owners (DOs).
      There were no significant differences in moderate, vigorous, or total PA minutes
      between DOs and non-dog owners. There was a significant difference in light PA
      minutes in favor of DOs (153 vs 112 minutes; 95% CI = 4 to 77; P = .030),
      however, this was largely restricted to breast cancer survivors (143 vs 79
      minutes; 95% CI = 25 to 102; P = .001) who also reported fewer vigorous PA
      minutes (18 vs 39 minutes; 95% CI = -42 to -1; P = .042). Survivors were more
      likely to be DOs if they had breast cancer (P = .054), a higher income (P =
      .021), radiation therapy (P = .029), chemotherapy (P = .010), were younger (P <
      .001), employed (P < .001), and a current smoker (P = .015). Few social cognitive
      variables were associated with DO. CONCLUSIONS: Dog ownership among cancer
      survivors was not associated with moderate-to-vigorous PA but was associated with
      light PA. Further research is necessary to determine if promoting dog ownership
      and dog walking among cancer survivors may increase PA and possibly improve
      health outcomes.

PMID- 27886413
TI  - Noble-Metal-Free Photocatalytic Hydrogen Evolution Activity: The Impact of Ball
      Milling Anatase Nanopowders with TiH2.
AB  - Ball milling TiO2 anatase together with TiH2 can create an effective
      photocatalyst. The process changes the lattice and electronic structure of
      anatase. Lattice deformation created by mechanical impact combined with hydride
      incorporation yield electronic gap-states close to the conduction band of
      anatase. These provide longer lifetimes of photogenerated charge carriers and
      lead to an intrinsic cocatalytic activation of anatase for H2 evolution.

PMID- 27886408
TI  - Role of ROCK2 in CD4+ cells in allergic airways responses in mice.
AB  - BACKGROUND: Rho kinases (ROCKs) contribute to allergic airways disease. ROCKs
      also play a role in lymphocyte proliferation and migration. OBJECTIVE: To
      determine the role of ROCK2 acting within CD4+ cells in allergic airways
      responses. METHODS: ROCK2-haploinsufficient (ROCK2+/- ) and wild-type mice were
      sensitized with ovalbumin (OVA). ROCK2+/- mice then received either CD4+ cells
      from ROCK2-sufficient OVA TCR transgenic (OT-II) mice or saline i.v. 48 h before
      challenge with aerosolized OVA. Wild-type mice received saline before challenge.
      Allergic airways responses were measured 48 h after the last challenge. Allergic
      airways responses were also assessed in mice lacking ROCK2 only in CD4+ cells
      (ROCK2CD4Cre mice) vs. control (CD4-Cre and ROCK2flox/flox ) mice. RESULTS: OVA
      induced increases in bronchoalveolar lavage lymphocytes, eosinophils, IL-13, IL
      5, and eotaxin were reduced in ROCK2+/- vs. wild-type mice, as were airway
      hyperresponsiveness and mucous hypersecretion. In ROCK2+/- mice, adoptive
      transfer with CD4+ cells from OT-II mice restored effects of OVA on lymphocytes,
      eosinophils, IL-13, IL-5, and mucous hypersecretion to wild-type levels, whereas
      eotaxin and airway hyperresponsiveness were not affected. ROCK2 inhibitors
      reduced IL-13-induced release of eotaxin from airway smooth muscle (ASM), similar
      to effects of these inhibitors on ASM contractility. Despite the ability of
      adoptive transfer to restore allergic airways inflammation in ROCK2-insufficient
      mice, allergic inflammation was not different in ROCK2CD4Cre vs. control mice.
      CONCLUSION: ROCK2 contributes to allergic airways responses likely via effects
      within ASM cells and within non-lymphocyte cells involved in lymphocyte
      activation and migration into the airways.

PMID- 27886415
TI  - Primary Mucormycosis of the Breast: A Rare Entity.

PMID- 27886414
TI  - Chronic ghrelin treatment reduced photophobia and anxiety-like behaviors in
      nitroglycerin- induced migraine: role of pituitary adenylate cyclase-activating
      polypeptide.
AB  - Chronic migraine is a debilitating disorder that has a significant impact on
      patients and society. Nearly all migraineurs frequently reported light
      sensitivity during a headache attack. Pituitary adenylate cyclase-activating
      polypeptide (PACAP) plays an important role in the activation of trigeminal
      system and migraine pain. To identify the effect of chronic ghrelin treatment on
      endogenous PACAP and associated symptoms of migraine, an experimental chronic
      migraine model was induced by intermittent intraperitoneal (i.p) injection of
      nitroglycerin (NTG). Photophobia and anxiety-like behaviors were determined in
      the modified elevated plus maze on days 2, 4, 6, 8, and 10 and in the light/dark
      box on days 3, 5, 7, 9, and 11. Blood levels of PACAP and cortisol were assessed
      by enzyme-linked immunosorbent (ELISA) kits. Chronic injection of NTG evoked
      photophobia and anxiety-like behaviors and treatment with ghrelin (150 MUg/kg)
      for 11 days effectively attenuated photophobia and anxiety-like behaviors in the
      both paradigms. We further found that NTG increased the blood levels of PACAP and
      cortisol, which was significantly reduced by ghrelin treatment. Additionally,
      staining with Hematoxylin and Eosin (H&E) revealed that ghrelin reduced NTG
      induced increase in the number of satellite glial cells in the trigeminal
      ganglion. Furthermore, for the first time we showed that repeated administrations
      of NTG increased white blood cell (WBC) counts and mean platelet volume (MPV),
      and decreased platelet counts. These results indicated that ghrelin decreased
      migraine associated symptoms possibly through attenuating endogenous PACAP and
      cortisol levels. Therefore, ghrelin may hold therapeutic potentialities in
      managing the chronic migraine.

PMID- 27886417
TI  - Staphylococcus aureus requires at least one FtsK/SpoIIIE protein for correct
      chromosome segregation.
AB  - Faithful coordination between bacterial cell division and chromosome segregation
      in rod-shaped bacteria, such as Escherichia coli and Bacillus subtilis, is
      dependent on the DNA translocase activity of FtsK/SpoIIIE proteins, which move
      DNA away from the division site before cytokinesis is completed. However, the
      role of these proteins in chromosome partitioning has not been well studied in
      spherical bacteria. Here, it was shown that the two Staphylococcus aureus
      FtsK/SpoIIIE homologues, SpoIIIE and FtsK, operate in independent pathways to
      ensure correct chromosome management during cell division. SpoIIIE forms foci at
      the centre of the closing septum in at least 50% of the cells that are close to
      complete septum synthesis. FtsK is a multifunctional septal protein with a C
      terminal DNA translocase domain that is not required for correct chromosome
      management in the presence of SpoIIIE. However, lack of both SpoIIIE and FtsK
      causes severe nucleoid segregation and morphological defects, showing that the
      two proteins have partially redundant roles in S. aureus.

PMID- 27886416
TI  - A Case of Solitary Well-Differentiated Papillary Mesothelioma with Invasive Foci
      in the Pleura.
AB  - Well-differentiated papillary mesothelioma (WDPM) is a rare, distinct tumor
      consisting of mesothelial cells with a papillary architecture, bland cytological
      features, and a tendency toward superficial spread without invasion. Rare cases
      with superficial invasion are termed WDPM with invasive foci. We report a case of
      solitary WDPM with invasive foci in the pleura. A 61-year-old woman presented
      with a lung adenocarcinoma. A small papillary lesion measuring 29 * 10 * 8 mm was
      incidentally found in the parietal pleura during a lobectomy for the lung
      adenocarcinoma. The fibrovascular core of the small papillary lesion was
      surrounded by a single layer of cuboidal cells with mild to moderate atypia and
      large nucleoli. Atypical mesothelial cells focally invaded the submesothelial
      layer. The cells of the papillary lesion were positive for cytokeratins and
      mesothelial markers. The Ki67 index was <1 %. The lesion did not show p16 loss on
      fluorescence in situ hybridization. We could not detect atypical mesothelial
      cells in the specimen from an extrapleural pneumonectomy. WDPM with invasive foci
      is prone to multifocality; however, our case represents a solitary case in the
      pleura.

PMID- 27886418
TI  - Surviving Triple Trouble: Synchronous Breast and Cervical Cancer, HIV Infection
      and Myocardial Infarction.
AB  - Breast and cervical cancer are the two most common cancers in female. However,
      owing to the contrasting risk factors, synchronous breast and cervical cancer has
      very rarely been reported. However, noncommunicable disease like cardiovascular
      disease and different infections has tended to make situations complicated
      because of complex interaction. In recent years, such cases are being seen
      frequently and their management is challenging. We report such a case of
      synchronous breast and cervical cancer complicated by HIV infection and
      myocardial infarction. This highlights the importance of a wide spectrum of
      clinical knowledge and skill and interdisciplinary coordination.

PMID- 27886419
TI  - Functional characterization of a novel loss-of-function mutation of PRPS1 related
      to early-onset progressive nonsyndromic hearing loss in Koreans (DFNX1):
      Potential implications on future therapeutic intervention.
AB  - BACKGROUND: The symptoms of phosphoribosyl pyrophosphate synthetase 1 (PRPS1)
      deficiency diseases have been reported to be alleviated by medication. In the
      present study, we report biochemical data that favor PRPS1 deficiency-related
      hearing loss as a potential target for pharmaceutical treatment. METHODS: We
      recruited 42 probands from subjects aged less than 15 years with a moderate
      degree of nonsyndromic autosomal-recessive or sporadic sensorineural hearing loss
      (SNHL) in at least one side. Molecular genetic testing, including targeted exome
      sequencing (TES) of 129 genes for deafness, and in silico prediction were
      performed. RESULTS: A strong candidate variant (p.A82P) of PRPS1 is co-segregated
      with SNHL in X-linked recessive inheritance from one Korean multiplex SNHL
      family. Subsequent measurement of in vitro enzymatic activities of PRPS1 from
      erythrocytes of affected and unaffected family members, as well as unrelated
      normal controls, confirmed a pathogenic role of this variant. In detail, compared
      to normal hearing controls (0.23-0.26 nmol/ml/h), the proband, the affected
      sibling and their normal hearing mother demonstrated a significantly decreased
      PRPS1 enzymatic activity (0.07, 0.03 and 0.11 nmol/ml/h, respectively). This
      novel loss-of-function mutation of PRPS1 (p.A82P) is the ninth and sixth most
      reported mutation in the world and in Asia, respectively. CONCLUSIONS: DFNX1 was
      found to account for approximately 2.4% (1/42) of moderate SNHL in a Korean
      pediatric population. Confirmation of PRPS1 activity deficiency and an audiologic
      phenotype that initially begins in a milder form of SNHL, as in our family,
      should indicate the need for rigorous genetic screening as early as possible.

PMID- 27886420
TI  - Posterior tibial tendinopathy associated with matrix metalloproteinase 13
      promoter genotype and haplotype.
AB  - BACKGROUND: Posterior tibial tendon (PTT) is particularly vulnerable and its
      insufficiency is recognized as the main cause of adult acquired flat foot. Some
      patients have a predisposition without a clinically recognized cause, suggesting
      that individual characteristics play an important role in tendinopathy. The
      present study investigated whether genetic variants in matrix metalloproteinases
      (MMPs) are associated with PTT dysfunction. METHODS: One hundred women who
      presented PTT dysfunction, with histopathological examination of the tendon and
      magnetic resonance imaging (MRI) confirming tendinopathy, as well as 100
      asymptomatic women who presented intact PPT as assessed by MRI and constituting
      the control group, were evaluated for MMP-13 g.-77 A > G (rs2252070)
      polymorphism, individually and in haplotypes, as well as in combination with MMP
      1 g.-519 A > G (rs1144393), MMP-1 g.-1607 G > GG (rs1799750) and MMP-8 g.-799 C >
      T (rs11225395) polymorphisms with PTT dysfunction. Genomic DNA was extracted from
      the saliva and genotypes were obtained by polymerase chain reaction-restriction
      fragment length polymorphism. Statistical analysis of the results included a Mann
      Whitney U-test, Fisher's exact test, multiple logistic regression, chi-squared
      and SNPstats software (http://bioinfo. iconcologia.net/snpstats/start.htm). p <
      0.05 was considered statistically significant. RESULTS: The A allele frequency
      (MMP-13 g.-77 A > G (rs2252070) polymorphism) was significantly higher in the
      case group (76% and 61%, respectively; p = 0.010, odds ratio = 2.02; 95%
      confidence interval = 1.32-3.12). The genotype distribution was also
      significantly different between groups (p = 0.001, odds ratio = 2.82; 95%
      confidence interval = 1.58-5.02). Global haplotype analysis indicated a
      significant difference between both groups. CONCLUSIONS: In conclusion, these
      findings indicate that MMP-13 g.-77 A > G (rs2252070) polymorphism individually,
      as well as its haplotypes MMP-1 g.-519 A > G (rs1144393), MMP-1 g.-1607 G > GG
      (rs1799750) and MMP-8 g.-799 C > T (rs11225395), may contribute to PTT
      dysfunction.

PMID- 27886421
TI  - Pathophysiology of dyspnoea in acute pulmonary embolism: A cross-sectional
      evaluation.
AB  - BACKGROUND AND OBJECTIVE: Dyspnoea in pulmonary embolism (PE) remains poorly
      characterized. Little is known about how to measure intensity or about the
      underlying mechanisms that may be related to ventilatory abnormalities, alveolar
      dead space ventilation or modulating factors such as psychological modulate. We
      hypothesized that dyspnoea would mainly be associated with pulmonary vascular
      obstruction and its pathophysiological consequences, while the sensory-affective
      domain of dyspnoea would be influenced by other factors. METHODS: We undertook a
      prospective study of 90 consecutive non-obese patients (mean +/- SD age: 49 +/-
      16 years, 41 women) without cardiorespiratory disease. All patients were
      hospitalized with symptoms for <15 days and a confirmed PE (multi-detector
      computed tomography (MDCT) scan, n = 87 and high-probability
      ventilation/perfusion scan, n = 3). Patients underwent assessment of dyspnoea
      using the Borg score, modified Medical Research Council (mMRC) scale, assessment
      of psychological trait, state of anxiety and depression and chest pain via the
      Visual Analogical Scale at the time of maximum dyspnoea. Functional evaluations
      such as the quantitative ventilation-perfusion lung scan, echocardiography,
      alveolar dead space fraction and tidal ventilation measurements were completed
      within 48 h of admission. RESULTS: Multivariate analyses demonstrated that
      dyspnoea was mainly linked to pulmonary vascular obstruction and/or its
      consequences such as raised pulmonary arterial pressure and chest pain. The
      sensory-affective domain of dyspnoea showed additional determinants such as age,
      depression and breathing variability. CONCLUSION: Dyspnoea is mainly related to
      vascular consequences of PE such as increased pulmonary arterial pressure or
      chest pain. The sensory-affective domain of dyspnoea also correlates with age,
      depression and breathing variability.

PMID- 27886422
TI  - Update in respiratory sleep disorders: Prologue to a modern review series.

PMID- 27886423
TI  - An approach for identifying cryptic barriers to gene flow that limit species'
      geographic ranges.
AB  - Species' geographic range limits are most often not demarcated by obvious
      dispersal barriers. Poor-quality habitat at the edge of a species' range can
      prevent range expansion by preventing outward migration or through reducing
      adaptive potential resulting from decreased genetic diversity. We identified
      habitat variables that constrain gene flow across the entire geographic range of
      an endemic salamander (Ambystoma barbouri) in the eastern United States, and we
      tested whether increased resistance resulting from these variables provides
      cryptic dispersal barriers at the range edges. Using polymorphic microsatellite
      loci, we first identified three genetic clusters that are separated by the Ohio
      and Kentucky rivers. Through a combination of landscape genetic analyses and
      generalized dissimilarity modelling, we then classified variables that (i)
      restrict gene flow in each of the genetic clusters across the geographic
      distribution of A. barbouri and (ii) become more common towards the peripheries
      of the distribution. A decrease in limestone availability and an increase in
      growing season precipitation were correlated with high resistance to gene flow
      across the range, and both became more common at the edges of the species'
      distribution. However, other landscape variables were more important for
      explaining variation in geneflow rates in different portions of the range, such
      as increased mean annual temperature and frost-free period in the south vs.
      growing season precipitation in the north. Taken together, these results suggest
      that there are both range-wide and regionally specific cryptic habitat barriers
      preventing geographic range expansion. Species 'geographic range limits are
      probably governed by a set of ecological and evolutionary factors, and our
      landscape genetic approach could be applied to gain additional insight into many
      systems.

PMID- 27886424
TI  - PGMA-Based Star-Like Polycations with Plentiful Hydroxyl Groups Act as Highly
      Efficient miRNA Delivery Nanovectors for Effective Applications in Heart
      Diseases.

PMID- 27886425
TI  - Template-Directed Directionally Solidified Three-Dimensionally Mesostructured
      AgCl-KCl Eutectic Photonic Crystals.

PMID- 27886426
TI  - Retraction Statement: "High-Volumetric Performance Aligned Nano-Porous Microwave
      Exfoliated Graphite Oxide-based Electrochemical Capacitors" and "Aligned Nano
      Porous Microwave Exfoliated Graphite Oxide Ionic Actuators with High Strain and
      Elastic Energy Density".
AB  - These articles first published on 15 August 2013 and 21 August 2013 on the Wiley
      Online Library have been retracted at the request of the Research Integrity
      Officer (RIO) of The Pennsylvania State University, in agreement with the
      corresponding authors, the journal's Editor-in-Chief, and Wiley-VCH Verlag GmbH &
      Co. KGaA, because portions of the reported results cannot be considered reliable
      or reproducible. Following an investigation by the RIO of The Pennsylvania State
      University, it was found that the data in Figure 2a,b and Figure S1a,b
      (Supporting Information) of the article with DOI: 10.1002/adma.201301243, and
      Figure S3 (Supporting Information) of the article with DOI:
      10.1002/adma.201301370 were falsified. Data regarding the carbon electrode
      material, A-aMEGO, reported to have a density of 1.15 g cm-3 , in the article
      with DOI: 10.1002/adma.201301243, were falsified. The RIO of The Pennsylvania
      State University confirms that the investigation found that the mentioned data
      were falsified by the first author. No findings of research misconduct were made
      against the co-authors of these publications. [1] M. Ghaffari, Y. Zhou, H. Xu, M.
      Lin, T. Y. Kim, R. S. Ruoff, Q. M. Zhang, Adv. Mater. 25: 2013, 4879.
      doi:10.1002/adma.201301243 [2] M. Ghaffari, W. Kinsman, Y. Zhou, S. Murali, Q.
      Burlingame, M. Lin, R. S. Ruoff, Q. M. Zhang, Adv. Mater. 25: 2013, 6277.
      doi:10.1002/adma.201301370.

PMID- 27886427
TI  - Culture-negative fever after pancreas transplantation.

PMID- 27886429
TI  - Assessing healthcare quality using routine data: evaluating the performance of
      the national tuberculosis programme in South Africa.
AB  - OBJECTIVE: To assess the performance of healthcare facilities by means of
      indicators based on guidelines for clinical care of TB, which is likely a good
      measure of overall facility quality. METHODS: We assessed quality of care in all
      public health facilities in South Africa using graphical, correlation and locally
      weighted kernel regression analysis of routine TB test data. RESULTS: Facility
      performance falls short of national standards of care. Only 74% of patients with
      TB provided a second specimen for testing, 18% received follow-up testing and 14%
      received drug resistance testing. Only resistance testing rates improved over
      time, tripling between 2004 and 2011. National awareness campaigns and changes in
      clinical guidelines had only a transient impact on testing rates. The poorest
      performing facilities remained at the bottom of the rankings over the period of
      study. CONCLUSION: The optimal policy strategy requires both broad-based policies
      and targeted resources to poor performers. This approach to assessing facility
      quality of care can be adapted to other contexts and also provides a low-cost
      method for evaluating the effectiveness of proposed interventions. Devising
      targeted policies based on routine data is a cost-effective way to improve the
      quality of public health care provided.

PMID- 27886428
TI  - Immune reactivity after adenoviral-mediated aquaporin-1 cDNA transfer to human
      parotid glands.
AB  - OBJECTIVES: The purpose of this study was to examine the humoral and cellular
      immune reactivity to adenoviral vector (AdhAQP1) administration in the human
      parotid gland over the first 42 days of a clinical gene therapy trial. METHODS:
      Of eleven treated subjects, five were considered as positive responders (Baum et
      al, 2012). Herein, we measured serum neutralizing antibody titers, circulating
      cytotoxic lymphocytes, and lymphocyte proliferation in peripheral blood
      mononuclear cells. Additionally, after adenoviral vector stimulation of
      lymphocyte proliferation, we quantified secreted cytokine levels. RESULTS:
      Responders showed little to modest immune reactivity during the first 42 days
      following gene transfer. Additionally, baseline serum neutralizing antibody
      titers to serotype 5-adenovirus generally were not predictive of a subject's
      response to parotid gland administration of AdhAQP1. Cytokine profiling from
      activated peripheral blood mononuclear cells could not distinguish responders and
      non-responders. CONCLUSIONS: The data are the first to describe immune responses
      after adenoviral vector administration in a human parotid gland. Importantly, we
      found that modest (2-3 fold) changes in systemic cell-mediated immune reactivity
      did not preclude positive subject responses to gene transfer. However, changes
      beyond that level likely impeded the efficacy of gene transfer.

PMID- 27886430
TI  - The muddle of ages, turnover, transit, and residence times in the carbon cycle.
AB  - Comparisons among ecosystem models or ecosystem dynamics along environmental
      gradients commonly rely on metrics that integrate different processes into a
      useful diagnostic. Terms such as age, turnover, residence, and transit times are
      often used for this purpose; however, these terms are variably defined in the
      literature and in many cases, calculations ignore assumptions implicit in their
      formulas. The aim of this opinion piece was i) to make evident these
      discrepancies and the incorrect use of formulas, ii) highlight recent results
      that simplify calculations and may help to avoid confusion, and iii) propose the
      adoption of simple and less ambiguous terms.

PMID- 27886431
TI  - Music interventions for dental anxiety.
AB  - Anxiety is a significant issue in the dental care of adults and children. Dental
      anxiety often leads to avoidance of dental care which may result in significant
      deterioration of oral and dental health. Non-pharmacological anxiety management
      interventions such as music listening are increasingly used in dental care.
      Although efficacy for music's anxiolytic effects has been established for pre
      operative anxiety, findings regarding the use of music listening for dental
      anxiety are inconclusive, especially for children. The use of music for passive
      distraction may not be adequate for children and highly anxious adults. Instead,
      interventions offered by a trained music therapist may be needed to optimize
      music's anxiolytic impact. Music therapy interventions are individualized to the
      patient's presenting needs and geared at enhancing patients' active engagement in
      the management of their anxiety. Interventions may include (i) active refocusing
      of attention, (ii) music-guided deep breathing, (iii) music-assisted relaxation,
      and (iv) music-guided imagery. In addition, music therapists can teach patients
      music-based anxiety management skills prior to dental treatments, offer them the
      opportunity to express emotions related to the upcoming procedure, and help them
      gain a sense of control and safety. Clinical guidelines for the use of music
      listening by dental practitioners are offered.

PMID- 27886432
TI  - Long-term nucleos(t)ide analog(s) monoprophylaxis in Delta coinfected liver
      transplant recipients.

PMID- 27886433
TI  - The Burkholderia cenocepacia peptidoglycan-associated lipoprotein is involved in
      epithelial cell attachment and elicitation of inflammation.
AB  - The Burkholderia cepacia complex (Bcc) is a group of Gram-negative opportunistic
      pathogens causing infections in people with cystic fibrosis (CF). Bcc is highly
      antibiotic resistant, making conventional antibiotic treatment problematic. The
      identification of novel targets for anti-virulence therapies should improve
      therapeutic options for infected CF patients. We previously identified that the
      peptidoglycan-associated lipoprotein (Pal) was immunogenic in Bcc infected CF
      patients; however, its role in Bcc pathogenesis is unknown. The virulence of a
      pal deletion mutant (Deltapal) in Galleria mellonella was 88-fold reduced (p <
      .001) compared to wild type. The lipopolysaccharide profiles of wild type and
      Deltapal were identical, indicating no involvement of Pal in O-antigen transport.
      However, Deltapal was more susceptible to polymyxin B. Structural elucidation by
      X-ray crystallography and calorimetry demonstrated that Pal binds peptidoglycan
      fragments. Deltapal showed a 1.5-fold reduced stimulation of IL-8 in CF
      epithelial cells relative to wild type (p < .001), demonstrating that Pal is a
      significant driver of inflammation. The Deltapal mutant had reduced binding to
      CFBE41o- cells, but adhesion of Pal-expressing recombinant E. coli to CFBE41o-
      cells was enhanced compared to wild-type E. coli (p < .0001), confirming that Pal
      plays a direct role in host cell attachment. Overall, Bcc Pal mediates host cell
      attachment and stimulation of cytokine secretion, contributing to Bcc
      pathogenesis.

PMID- 27886434
TI  - Integrated total pelvic floor ultrasound in pelvic floor defaecatory dysfunction.
AB  - AIM: Imaging for pelvic floor defaecatory dysfunction includes defaecation
      proctography. Integrated total pelvic floor ultrasound (transvaginal,
      transperineal, endoanal) may be an alternative. This study assesses ultrasound
      accuracy for the detection of rectocele, intussusception, enterocele and
      dyssynergy compared with defaecation proctography, and determines if ultrasound
      can predict symptoms and findings on proctography. Treatment is examined. METHOD:
      Images of 323 women who underwent integrated total pelvic floor ultrasound and
      defaecation proctography between 2011 and 2014 were blindly reviewed. The size
      and grade of rectocele, enterocele, intussusception and dyssynergy were noted on
      both, using proctography as the gold standard. Barium trapping in a rectocele or
      a functionally significant enterocele was noted on proctography. Demographics and
      Obstructive Defaecation Symptom scores were collated. RESULTS: The positive
      predictive value of ultrasound was 73% for rectocele, 79% for intussusception and
      91% for enterocele. The negative predictive value for dyssynergy was 99%.
      Agreement was moderate for rectocele and intussusception, good for enterocele and
      fair for dyssynergy. The majority of rectoceles that required surgery (59/61) and
      caused barium trapping (85/89) were detected on ultrasound. A rectocele seen on
      both transvaginal and transperineal scanning was more likely to require surgery
      than if seen with only one mode (P = 0.0001). If there was intussusception on
      ultrasound the patient was more likely to have surgery (P = 0.03). An enterocele
      visualized on ultrasound was likely to be functionally significant on
      proctography (P = 0.02). There was, however, no association between findings on
      imaging and symptoms. CONCLUSION: Integrated total pelvic floor ultrasound
      provides a useful screening tool for women with defaecatory dysfunction such that
      defaecatory imaging can avoided in some.

PMID- 27886436
TI  - Factors that hinder or enable maternal health strategies to reduce delays in
      rural and pastoralist areas in Ethiopia.
AB  - OBJECTIVES: To document factors that hinder or enable strategies to reduce the
      first and second delays of the Three Delays in rural and pastoralist areas in
      Ethiopia. METHODS: A key informant study was conducted with 44 Health Extension
      Workers in Afar Region, Kafa Zone (Southern Nation, Nationalities and Peoples'
      Region), and Adwa Woreda (Tigray Region). Health Extension Workers were trained
      to interview women and ask for stories about their recent experiences of birth.
      We interviewed the Health Extension Workers about their experiences referring
      women for Skilled Birth Attendance and Emergency Obstetric and Newborn Care. Data
      were analysed using thematic analysis. RESULTS: Themes related to reducing the
      first delay, such as the tradition of home birth, decision-making, distance and
      unavailability of transport, did not differ between the three locations. Themes
      related to reducing the second delay differed substantially. Health Extension
      Workers in Adwa Woreda were more likely to call ambulances due to support from
      the Health Development Army and a functioning referral system. In Kafa Zone, some
      Health Extension Workers were discouraged from calling ambulances as they were
      used for other purposes. In Afar Region, few Health Extension Workers were called
      to assist women as most women give birth at home with Traditional Birth
      Attendants unless they need to travel to health facilities for Emergency
      Obstetric and Newborn Care. CONCLUSIONS: Initiatives to reduce delays can improve
      access to maternal health services, especially when Health Extension Workers are
      supported by the Health Development Army and a functioning referral system, but
      district (woreda) health offices should ensure that ambulances are used as
      intended.

PMID- 27886435
TI  - A multicomponent quality improvement intervention to improve blood pressure and
      reduce racial disparities in rural primary care practices.
AB  - The Southeastern United States has the highest prevalence of hypertension and
      African Americans have disproportionately worse blood pressure control. The
      authors sought to evaluate the effect of a multicomponent practice-based quality
      improvement intervention on lowering mean systolic blood pressure (SBP) at 12 and
      24 months compared with baseline among 525 patients, and to assess for a
      differential effect of the intervention by race (African Americans vs white). At
      12 months, both African Americans (-5.0 mm Hg) and whites (-7.8 mm Hg) had a
      significant decrease in mean SBP compared with baseline, with no significant
      between-group difference. Similarly, at 24 months, mean SBP decreased in both
      African Americans (-6.0 mm Hg) and whites (-7.2 mm Hg), with no significant
      difference between groups. Notably, no significant racial disparity in mean SBP
      at baseline was shown. The intervention was effective in lowering mean SBP in
      both African Americans and whites but there was no differential effect of the
      intervention by race.

PMID- 27886437
TI  - The microRNA-99 family modulates hepatitis B virus replication by promoting IGF
      1R/PI3K/Akt/mTOR/ULK1 signaling-induced autophagy.
AB  - MicroRNAs are small highly conserved noncoding RNAs that are widely expressed in
      multicellular organisms and participate in the regulation of various cellular
      processes including autophagy and viral replication. Evidently, microRNAs are
      able to modulate host gene expression and thereby inhibit or enhance hepatitis B
      virus (HBV) replication. The miR-99 family members are highly expressed in the
      liver. Interestingly, the plasma levels of miR-99 family in the peripheral blood
      correspond with HBV DNA loads. Thus, we asked whether the miR-99 family regulated
      HBV replication and analyzed the underlying molecular mechanism. Compared with
      primary hepatocytes, miR-99 family expression was downregulated in hepatoma
      cells. Transfection of miR-99a, miR-99b, and miR-100 markedly increased HBV
      replication, progeny secretion, and antigen expression in hepatoma cells.
      However, miR-99 family had no effect on HBV transcription and HBV promoter
      activities, suggesting that they regulate HBV replication at posttranscriptional
      steps. Consistent with bioinformatic analysis and recent reports, ectopic
      expression of miR-99 family attenuated IGF-1R/Akt/mTOR pathway signaling and
      repressed insulin-stimulated activation in hepatoma cells. Moreover, the
      experimental data demonstrated that the miR-99 family promoted autophagy through
      mTOR/ULK1 signaling and thereby enhanced HBV replication. In conclusion, the miR
      99 family promotes HBV replication posttranscriptionally through IGF
      1R/PI3K/Akt/mTOR/ULK1 signaling-induced autophagy.

PMID- 27886438
TI  - Self-Assembly of Bolaamphiphilic Molecules.
AB  - The current buzzword in science and technology is self-assembly and molecular
      self-assembly is one of the most prominent fields as far as research in chemical
      and biological sciences is concerned. Generally, self-assembly of molecules
      occurs through weak non-covalent interactions like hydrogen bonding, pi-pi
      stacking, hydrophobic effects, etc. Inspired by many natural systems consisting
      of self-assembled structures, scientists have been trying to understand their
      formation and mimic such processes in the laboratory to create functional "smart"
      materials, which respond to temperature, light, pH, electromagnetic field,
      mechanical stress, and/or chemical stimuli. These responses are usually
      manifested as remarkable changes from the molecular (e. g., conformational state,
      hierarchical order) to the macroscopic level (e. g., shape, surface properties).
      Many molecules such as peptides, viruses, and surfactants are known to self
      assemble into different structures. Among them, glycolipids are the new entries
      in the area of molecules that are being investigated for their self-assembly
      characteristics. Among the different classes of glycolipids like rhamnolipids and
      trehalose lipids, owing to their biological preparations and their structural
      novelty, sophorolipids (SLs) are evoking greater interest among researchers.
      Sophorolipids are a class of asymmetric bolas bearing COOH groups at one end and
      sophorose (dimeric glucose linked by an unusual beta(1->2) linkage). The extreme
      membrane stability of Archaea, attributed to the membrane-spanning bolas
      (tetraether glycolipids), has inspired chemists to unravel the molecular designs
      that underpin the self-assembly of bolaamphiphilic molecules. Apart from these
      self-assembled structures, bolaamphiphiles find applications in many fields such
      as drug delivery, membrane mimicking, siRNA therapies, etc. The first part of
      this Personal Account presents some possible self-assembled structures of
      bolaamphiphiles and their mechanism of formation. The later part covers our work
      on one of the typical bolaamphiphiles known as sophorolipids.

PMID- 27886439
TI  - Efficacy of accelerated hydrogen peroxide(r) disinfectant on foot-and-mouth
      disease virus, swine vesicular disease virus and Senecavirus A.
AB  - AIMS: In a laboratory, disinfectants used to inactivate pathogens on contaminated
      surfaces and to prevent spread of diseases often have adverse side effects on
      personnel and the environment. It is, therefore, essential to find safer, fast
      acting and yet effective disinfectants. The objective of this study was to
      evaluate an accelerated hydrogen peroxide(r) (AHP(r) )-based disinfectant against
      high consequence foreign animal disease pathogens such as foot-and-mouth disease
      virus (FMDV) and swine vesicular disease virus (SVDV), as well as Senecavirus A
      (SVA), which causes similar lesions as FMDV and SVDV. METHODS AND RESULTS: We
      tested varying dilutions and contact times of AHP against FMDV, SVDV and SVA by
      the standard US EPA and modified methods. AHP was effective against all three
      viruses, albeit at a higher concentration and double the manufacturer recommended
      contact time when testing wet films of SVDV. CONCLUSIONS: AHP is an effective
      disinfectant against FMDV, SVDV and SVA. SIGNIFICANCE AND IMPACT OF THE STUDY:
      AHP-based disinfectant can, therefore, be used in high containment laboratories
      working with FMDV, SVDV and related pathogens.

PMID- 27886440
TI  - The forgotten place of radioembolization for the treatment of hepatocellular
      carcinoma with portal vein tumour thrombosis.

PMID- 27886441
TI  - Divergent Total Synthesis of Atisane-Type Diterpenoids.
AB  - Atisane-type diterpenoids are the principal constituent of tetracyclic C20 
      diterpenoids, widely isolated from the plant kingdom with varying degrees of
      structural complexity and pharmacological activity. The tetracarbocyclic system
      with the unique bicyclo[2.2.2]octane skeleton of this natural product family has
      generated interest within the synthetic community. Divergent total synthesis is
      an effective tactic to synthesize several atisane-type diterpenoids using
      structural interconversion from a common intermediate. This account summarizes
      the divergent total synthesis of atisane-type diterpenoids.

PMID- 27886442
TI  - Eosinophilic pneumonia as complication of linear IgA dermatosis treated with
      dapsone.

PMID- 27886443
TI  - Introducing Barium in Transition Metal Oxide Frameworks: Impact upon
      Superconductivity, Magnetism, Multiferroism and Oxygen Diffusion and Storage.
AB  - The role of barium in the structural chemistry of some transition metal oxides of
      the series "Cu, Mn, Fe,Co" is reviewed, based on its size effect and its
      particular chemical bonding. Its impact upon various properties,
      superconductivity, magnetism, multiferroism, oxygen storage is emphasized.

PMID- 27886444
TI  - Incidence and classification of cutaneous manifestations in rheumatoid arthritis.
AB  - BACKGROUND AND OBJECTIVE: There have only been few studies examining rheumatoid
      arthritis (RA)-related skin manifestations in larger patient populations. Herein,
      we present current data on the prevalence and spectrum of cutaneous lesions in
      RA, addressing disease activity scores, anti-CCP antibodies as well as novel
      pharmacological approaches. PATIENTS AND METHODS: Between November 2006 and July
      2007, 214 patients with RA treated at the Division of Rheumatology, University
      Hospital Jena, Germany, were prospectively examined. RESULTS: 27.5 % of patients
      exhibited RA-related skin manifestations, almost all of which were rheumatoid
      nodules. These lesions occurred significantly more frequently in patients with
      longstanding disease, those testing positive for rheumatoid factor and anti-CCP
      antibodies, as well as individuals on leflunomide and TNF-alpha antagonists.
      Comparatively lower prevalence rates were observed for palisading neutrophilic
      and granulomatous dermatitis and rheumatoid vasculitis. CONCLUSIONS: Despite
      increasingly early treatment of RA and use of novel pharmacological agents, there
      is a high prevalence of rheumatoid nodules, which represent the most common
      cutaneous manifestation in RA. The higher prevalence of rheumatoid nodules in
      patients on leflunomide and TNF-alpha antagonists might be an indication that
      pharmacological treatment has only limited effects on their formation, possibly
      due to pathogenetic pathways that are only inadequately affected by drug
      therapies. By contrast, palisading neutrophilic and granulomatous dermatitis and
      rheumatoid vasculitis appear to respond better to novel pharmacological agents.

PMID- 27886445
TI  - Beard hair density increase. A possible role of topical tretinoin application?

PMID- 27886446
TI  - Mean platelet volume as a marker for differentiating disease flare from infection
      in Behcet's disease.
AB  - AIM: The aim of this study was to investigate the association between mean
      platelet volume (MPV) and clinical manifestations, disease activity or infection
      in patients with Behcet's disease (BD). METHODS: In total, 193 patients diagnosed
      with BD according to the international criteria for BD were enrolled. Demographic
      data, clinical manifestations and laboratory results were collected by medical
      interviews and reviewing medical records. RESULTS: The female : male ratio was 2
      : 1 and the age of symptom onset was 32.2 +/- 11.1 years. The age at diagnosis of
      BD was 44.7 +/- 11.1 years and the follow-up duration was 4.7 +/- 3.8 years. MPV
      at diagnosis were significantly lower than of age and sex-matched controls (8.2
      +/- 1.2 vs. 8.6 +/- 1.2 fL, P < 0.0001). Lower MPV was not related to organ
      involvement except skin diseases. During follow-up, MPV was lower in BD flare
      than in stable BD (8.2 +/- 1.4 vs. 9.1 +/- 1.4 fL, P < 0.0001) in the same
      patients. MPVs were significantly higher in cases of accompanying infections than
      in those with both BD flare and stable BD (9.3 +/- 1.4 vs. 8.1 +/- 1.3 fL, P =
      0.018 and 9.7 +/- 1.4 vs. 8.8 +/- 1.0 fL, P = 0.001, respectively). CONCLUSIONS:
      MPV was significantly lower in patients with BD than controls. MPV declined in BD
      flare and increased in cases of infection in same patients. MPV may be useful as
      a marker of BD activity and its monitoring can be helpful for differentiating BD
      flare from infection in BD patients.

PMID- 27886448
TI  - Comment on: "Effect on Sexual Function of Patients and Patients' Spouses After
      Midurethal Sling Procedure for Stress Urinary Incontinence: A Prospective Single
      Center Study".

PMID- 27886447
TI  - Synthesis of novel quaternary silica hybrid bioactive microspheres.
AB  - PURPOSE: To survey the preparation of novel hybrid microspheres of quaternary
      silicate glassy composition (SiO2 ?P2 O5 ?CaO?Na2 O) and the prospect of using
      them as an osteogenic system with enhanced bioactive properties for the
      development of hydroxyapatite. METHOD: In line with our previous synthetic
      procedure a two-step process was followed, wherein polystyrene (PS) microspheres
      were prepared by the emulsifier free-emulsion polymerization method and
      constituted the core for the sol-gel coating of the silicate inorganic shell. The
      development of the hybrid microspheres was based on silane and phosphate
      precursors and was assesses at different ratio of ethanol/water (of 9/1, 4/1, and
      2/1, in mL) and at varied ammonia concentration of 4.8-1.0 mL. RESULTS: The
      hybrid microspheres had an average size ranged between 350 and 550 nm according
      to SEM, depending on the ethanol/water solution rate and ammonia content. The
      final microspheres probably exhibited a porous-like structure through the
      formation of diffused voids along with the low carbon content of the EDX
      analysis, which could be regulated by the catalyst content. The hybrid
      microspheres exhibited effective in vitro bioactivity assessed in simulated body
      fluids (SBF). CONCLUSION: Quaternary hybrid silica microspheres were effectively
      synthesized. The bioassay evaluation of the final microspheres revealed the rapid
      in vitro formation of a bone-like apatite layer. The results verify the
      bioactivity of the microspheres and promote further research of their suitability
      on regenerative treatment of bone abnormalities. (c) 2016 Wiley Periodicals, Inc.
      J Biomed Mater Res Part B: Appl Biomater, 106B: 112-120, 2018.

PMID- 27886450
TI  - Comprehending 3D Diagrams: Sketching to Support Spatial Reasoning.
AB  - Science, technology, engineering, and mathematics (STEM) disciplines commonly
      illustrate 3D relationships in diagrams, yet these are often challenging for
      students. Failing to understand diagrams can hinder success in STEM because
      scientific practice requires understanding and creating diagrammatic
      representations. We explore a new approach to improving student understanding of
      diagrams that convey 3D relations that is based on students generating their own
      predictive diagrams. Participants' comprehension of 3D spatial diagrams was
      measured in a pre- and post-design where students selected the correct 2D slice
      through 3D geologic block diagrams. Generating sketches that predicated the
      internal structure of a model led to greater improvement in diagram understanding
      than visualizing the interior of the model without sketching, or sketching the
      model without attempting to predict unseen spatial relations. In addition, we
      found a positive correlation between sketched diagram accuracy and improvement on
      the diagram comprehension measure. Results suggest that generating a predictive
      diagram facilitates students' abilities to make inferences about spatial
      relationships in diagrams. Implications for use of sketching in supporting STEM
      learning are discussed.

PMID- 27886449
TI  - Ordered Micro/Nanostructures with Geometric Gradient: From Integrated Wettability
      "Library" to Anisotropic Wetting Surface.
AB  - Geometric gradients within ordered micro/nanostructures exhibit unique wetting
      properties. Well-defined and ordered microsphere arrays with geometric gradient
      (OMAGG) are successfully fabricated through combining colloidal lithography and
      inclined reactive ion etching (RIE). During the inclined RIE, the graded etching
      rates in vertical direction of etcher chamber are the key to generating a
      geometric gradient. The OMAGG can be used as an effective mask for the
      preparation of micro/nanostructure arrays with geometric gradient by selective
      RIE. Through this strategy, a well-defined wettability "library" with graded
      silicon cone arrays is fabricated, and the possibility of screening one desired
      "book" from the designated wettability "library" is demonstrated. Meanwhile, the
      silicon cone arrays with geometric gradient (SCAGG) can be applied to control the
      wetting behavior of water after being modified by hydrophilic or hydrophobic
      chemical groups. Based on this result, a temperature-responsive wetting substrate
      is fabricated by modifying poly n-isopropyl acrylamide (PNIPAM) on the SCAGG.
      These wettability gradients have great potential in tissue engineering,
      microfluidic devices, and integrated sensors.

PMID- 27886452
TI  - Bioresorbable vascular scaffolds in coronary bifurcation lesions: The next
      frontiers?

PMID- 27886453
TI  - You can't get there from here.

PMID- 27886451
TI  - Activity of Fluorine-Containing Analogues of WC-9 and Structurally Related
      Analogues against Two Intracellular Parasites: Trypanosoma cruzi and Toxoplasma
      gondii.
AB  - Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas
      disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the
      mevalonate pathway of their host cells upon infection, which suggests that this
      host pathway could be a potential drug target. In this work, a number of
      compounds structurally related to WC-9 (4-phenoxyphenoxyethyl thiocyanate), a
      known squalene synthase inhibitor, were designed, synthesized, and evaluated for
      their effect on T. cruzi and T. gondii growth in tissue culture cells. Two
      fluorine-containing derivatives, the 3-(3-fluorophenoxy)- and 3-(4
      fluorophenoxy)phenoxyethyl thiocyanates, exhibited half-maximal effective
      concentration (EC50 ) values of 1.6 and 4.9 MUm, respectively, against
      tachyzoites of T. gondii, whereas they showed similar potency to WC-9 against
      intracellular T. cruzi (EC50 values of 5.4 and 5.7 MUm, respectively). In
      addition, 2-[3- (phenoxy)phenoxyethylthio]ethyl-1,1-bisphosphonate, which is a
      hybrid inhibitor containing 3-phenoxyphenoxy and bisphosphonate groups, has
      activity against T. gondii proliferation at sub-micromolar levels (EC50 =0.7
      MUm), which suggests a combined inhibitory effect of the two functional groups.

PMID- 27886454
TI  - A toast to no sternotomy.

PMID- 27886456
TI  - Bifurcation stenting with bioresorbable scaffolds: Quo vadis?

PMID- 27886455
TI  - Provisional rotablator for calcified lesions: The Russian roulette of PCI.

PMID- 27886458
TI  - To BAV or not to BAV, that is a TAVR question.

PMID- 27886457
TI  - Serenity, courage, and wisdom: The keys to successful coronary calcification
      treatment.

PMID- 27886459
TI  - Standardized experiments in mutant mice reveal behavioural similarity on 129S5
      and C57BL/6J backgrounds.
AB  - Behavioural analysis of mice carrying engineered mutations is widely used to
      identify roles of specific genes in components of the mammalian behavioural
      repertoire. The reproducibility and robustness of phenotypic measures has become
      a concern that undermines the use of mouse genetic models for translational
      studies. Contributing factors include low individual study power, non
      standardized behavioural testing, failure to address confounds and differences in
      genetic background of mutant mice. We have examined the importance of these
      factors using a statistically robust approach applied to behavioural data
      obtained from three mouse mutations on 129S5 and C57BL/6J backgrounds generated
      in a standardized battery of five behavioural assays. The largest confounding
      effect was sampling variation, which partially masked the genetic background
      effect. Our observations suggest that strong interaction of mutation with genetic
      background in mice in innate and learned behaviours is not necessarily to be
      expected. We found composite measures of innate and learned behaviour were
      similarly impacted by mutations across backgrounds. We determined that, for
      frequently used group sizes, a single retest of a significant result conforming
      to the commonly used P < 0.05 threshold results in a reproducibility of 60%
      between identical experiments. Reproducibility was reduced in the presence of
      strain differences. We also identified a P-value threshold that maximized
      reproducibility of mutant phenotypes across strains. This study illustrates the
      value of standardized approaches for quantitative assessment of behavioural
      phenotypes and highlights approaches that may improve the translational value of
      mouse behavioural studies.

PMID- 27886460
TI  - The 6th Sino-German Frontiers of Chemistry Symposium.
AB  - Bilateral Symposium: The Shanghai Institute of Organic Chemistry (SIOC) hosted
      the 6th Sino-German Frontiers of Chemistry Symposium from August 29 to September
      3, 2016. This event, co-organized by the Chinese Chemical Society (CCS) and the
      Gesellschaft Deutscher Chemiker (German Chemical Society), featured excellent
      talks by the invited early-career chemists of both countries and offered ample
      opportunities for discussions and making friends among the participants.

PMID- 27886461
TI  - Biomaterial-Based Implantable Devices for Cancer Therapy.
AB  - This review article focuses on the current local therapies mediated by implanted
      macroscaled biomaterials available or proposed for fighting cancer and also
      highlights the upcoming research in this field. Several authoritative review
      articles have collected and discussed the state-of-the-art as well as the
      advancements in using biomaterial-based micro- and nano-particle systems for drug
      delivery in cancer therapy. On the other hand, implantable biomaterial devices
      are emerging as highly versatile therapeutic platforms, which deserve an
      increased attention by the healthcare scientific community, as they are able to
      offer innovative, more effective and creative strategies against tumors. This
      review summarizes the current approaches which exploit biomaterial-based devices
      as implantable tools for locally administrating drugs and describes their
      specific medical applications, which mainly target resected brain tumors or brain
      metastases for the inaccessibility of conventional chemotherapies. Moreover, a
      special focus in this review is given to innovative approaches, such as combined
      delivery therapies, as well as to alternative approaches, such as scaffolds for
      gene therapy, cancer immunotherapy and metastatic cell capture, the later as
      promising future trends in implantable biomaterials for cancer applications.

PMID- 27886463
TI  - Association between recovery from Bell's palsy and body mass index.
AB  - BACKGROUND: Although many factors have been found to be involved in recovery from
      Bell's palsy, no study has investigated the association between recovery from
      Bell's palsy and obesity. This study therefore evaluated the association between
      recovery from Bell's palsy and body mass index (BMI). METHODS: Subjects were
      classified into five groups based on BMI (kg/m2 ). Demographic and clinical
      characteristics were compared among these groups. Assessed factors included sex,
      age, time from paralysis to visiting a hospital, the presence of comorbidities
      such as diabetes mellitus and hypertension, degree of initial facial nerve
      paralysis by House-Brackmann (H-B) grade and neurophysiological testing, and
      final recovery rate. RESULTS: Based on BMI, 37 subjects were classified as
      underweight, 169 as normal weight, 140 as overweight, 155 as obese and 42 as
      severely obese. Classification of the degree of initial facial nerve paralysis as
      moderate or severe, according to H-B grade and electroneurography, showed no
      difference in severity of initial facial paralysis among the five groups (P >
      0.05). However, the final recovery rate was significantly higher in the normal
      weight than in the underweight or obese group (P < 0.05). CONCLUSIONS: Obesity or
      underweight had no effect on the severity of initial facial paralysis, but the
      final recovery rate was lower in the obese and underweight groups than in the
      normal group.

PMID- 27886464
TI  - Investigation of the chemical markers for experiential quality evaluation of
      crude aconite by UHPLC-Q-TOF-MS.
AB  - J. Sep. Sci. 2016, 39, 4281-4289 DOI: 10.1002/jssc.201600567 Aconite, called
      tiger and wolf drug, is known in Traditional Chinese Medicine for its strong
      cardiac effect. In the past, the toxins extracted from aconite were used as arrow
      poisons to kill animals, hence the name "wolf's bane." To a certain extent, the
      wolf represents the medicinal characteristics of aconite: fierce, wild and
      intractable. The cover picture shows, besides the wolf head as the main element,
      a flow chart of our study and summarizes the main topics of our article.

PMID- 27886462
TI  - Loss of ppr3, ppr4, ppr6, or ppr10 perturbs iron homeostasis and leads to
      apoptotic cell death in Schizosaccharomyces pombe.
AB  - : Pentatricopeptide repeat (PPR) proteins characterized by tandem arrays of a
      degenerate 35-amino-acid repeat belong to a large family of RNA-binding proteins
      that are involved in post-transcriptional control of organelle gene expression.
      PPR proteins are ubiquitous in eukaryotes, and particularly prevalent in higher
      plants. Schizosaccharomyces pombe has 10 PPR proteins. Among them, ppr3, ppr4,
      ppr6, and ppr10 participate in mitochondrial post-transcriptional processes and
      are required for mitochondrial electron transport chain (ETC) function. In the
      present work, we showed that deletion of ppr3, ppr4, ppr6, or ppr10 led to
      apoptotic cell death, as revealed by DAPI and Annexin V-FITC staining. These
      mutants also exhibited elevated levels of reactive oxygen species (ROS). RNA
      sequencing (RNA-seq) and quantitative RT-PCR analyses revealed that deletion of
      ppr10 affected critical biological processes. In particular, a core set of genes
      involved in iron uptake and/or iron homeostasis was elevated in the Deltappr10
      mutant, suggesting an elevated level of intracellular iron in the mutant.
      Consistent with this notion, Deltappr3, Deltappr4, Deltappr6, and Deltappr10
      mutants exhibited increased sensitivity to iron. Furthermore, the iron chelator,
      bathophenanthroline disulfonic acid, but not the calcium chelator EGTA, nearly
      restored the viabilities of Deltappr3, Deltappr4, Deltappr6, and Deltappr10
      mutants, and reduced ROS levels in the mutants. These results show for the first
      time that deletion of a ppr gene leads to perturbation of iron homeostasis. Our
      results also suggest that disrupted iron homeostasis in Deltappr3, Deltappr4,
      Deltappr6, and Deltappr10 mutants may lead to an increase in the level of ROS and
      induction of apoptotic cell death in S. pombe. DATABASE: The RNA-seq data have
      been deposited in the National Center for Biotechnology Information (NCBI)
      BioProject database (accession number SRP091623) and Gene Expression Omnibus
      (GEO) database (accession number GSE90144).

PMID- 27886465
TI  - Deterministic Down-Converter and Continuous Photon-Pair Source within the Bad
      Cavity Limit.
AB  - The development, characterization, and control of N-photon sources are
      instrumental for quantum technological applications. This work constitutes a step
      forward in this direction, where we propose a cavity quantum electrodynamics
      setup designed for the generation of photon pairs. We identify both the regime
      where our system works as a deterministic down-converter of a single input photon
      and as an optimal two-photon source under weak continuous driving. We use both
      the scattering and master equation formalisms to characterize the system, and
      from their connection naturally arises a physical criterion characterizing when
      weakly driven systems behave as continuous antibunched two-photon sources. We
      also show that the outgoing photons share nontrivial quantum correlations in
      general. We provide a specific implementation based on state-of-the-art
      superconducting circuits, showing how our proposal is within the reach of current
      technologies. As an outlook, we show the proposal can be extended to achieve
      deterministic conversion of a single photon into N photons.

PMID- 27886467
TI  - Transport in Out-of-Equilibrium XXZ Chains: Exact Profiles of Charges and
      Currents.
AB  - We consider the nonequilibrium time evolution of piecewise homogeneous states in
      the XXZ spin-1/2 chain, a paradigmatic example of an interacting integrable
      model. The initial state can be thought of as the result of joining chains with
      different global properties. Through dephasing, at late times, the state becomes
      locally equivalent to a stationary state which explicitly depends on position and
      time. We propose a kinetic theory of elementary excitations and derive a
      continuity equation which fully characterizes the thermodynamics of the model. We
      restrict ourselves to the gapless phase and consider cases where the chains are
      prepared: (1) at different temperatures, (2) in the ground state of two different
      models, and (3) in the "domain wall" state. We find excellent agreement (any
      discrepancy is within the numerical error) between theoretical predictions and
      numerical simulations of time evolution based on time-evolving block decimation
      algorithms. As a corollary, we unveil an exact expression for the expectation
      values of the charge currents in a generic stationary state.

PMID- 27886466
TI  - Measuring the Degeneracy of Discrete Energy Levels Using a GaAs/AlGaAs Quantum
      Dot.
AB  - We demonstrate an experimental method for measuring quantum state degeneracies in
      bound state energy spectra. The technique is based on the general principle of
      detailed balance and the ability to perform precise and efficient measurements of
      energy-dependent tunneling-in and -out rates from a reservoir. The method is
      realized using a GaAs/AlGaAs quantum dot allowing for the detection of time
      resolved single-electron tunneling with a precision enhanced by a feedback
      control. It is thoroughly tested by tuning orbital and spin degeneracies with
      electric and magnetic fields. The technique also lends itself to studying the
      connection between the ground-state degeneracy and the lifetime of the excited
      states.

PMID- 27886468
TI  - Practical Receiver for Optimal Discrimination of Binary Coherent Signals.
AB  - We address the long-standing problem of discriminating coherent states with the
      minimum error rate. We show an optimum receiver for coherent states which admits
      a relatively simple implementation with current technologies. The receiver is
      based on multichannel splitting of the signal, followed by feed-forward signal
      displacement and photon-counting detection. We develop an optimal control
      strategy for a finite signal split and show convergence of the error rate to the
      Helstrom bound.

PMID- 27886469
TI  - Quantum Simulation of the Factorization Problem.
AB  - Feynman's prescription for a quantum simulator was to find a Hamitonian for a
      system that could serve as a computer. The Polya-Hilbert conjecture proposed the
      demonstration of Riemann's hypothesis through the spectral decomposition of
      Hermitian operators. Here we study the problem of decomposing a number into its
      prime factors, N=xy, using such a simulator. First, we derive the Hamiltonian of
      the physical system that simulates a new arithmetic function formulated for the
      factorization problem that represents the energy of the computer. This function
      rests alone on the primes below sqrt[N]. We exactly solve the spectrum of the
      quantum system without resorting to any external ad hoc conditions, also showing
      that it obtains, for x?sqrt[N], a prediction of the prime counting function that
      is almost identical to Riemann's R(x) function. It has no counterpart in analytic
      number theory, and its derivation is a consequence of the quantum theory of the
      simulator alone.

PMID- 27886470
TI  - Stability of High-Density Two-Dimensional Excitons against a Mott Transition in
      High Magnetic Fields Probed by Coherent Terahertz Spectroscopy.
AB  - We have performed time-resolved terahertz absorption measurements on photoexcited
      electron-hole pairs in undoped GaAs quantum wells in magnetic fields. We probed
      both unbound- and bound-carrier responses via cyclotron resonance and
      intraexciton resonance, respectively. The stability of excitons, monitored as the
      pair density was systematically increased, was found to dramatically increase
      with increasing magnetic field. Specifically, the 1s-2p_{-} intraexciton
      transition at 9 T persisted up to the highest density, whereas the 1s-2p feature
      at 0 T was quickly replaced by a free-carrier Drude response. Interestingly, at 9
      T, the 1s-2p_{-} peak was replaced by free-hole cyclotron resonance at high
      temperatures, indicating that 2D magnetoexcitons do dissociate under thermal
      excitation, even though they are stable against a density-driven Mott transition.

PMID- 27886471
TI  - Evidence for Marginal Stability in Emulsions.
AB  - We report the first measurements of the effect of pressure on vibrational modes
      in emulsions, which serve as a model for soft frictionless spheres at zero
      temperature. As a function of the applied pressure, we find that the density of
      states D(omega) exhibits a low-frequency cutoff omega^{*}, which scales linearly
      with the number of extra contacts per particle deltaz. Moreover, for
      omega<omega^{*}, our results are consistent with D(omega)~omega^{2}/omega^{*2}, a
      quadratic behavior whose prefactor is larger than what is expected from Debye
      theory. This surprising result agrees with recent theoretical findings [E.
      DeGiuli, A. Laversanne-Finot, G. A. During, E. Lerner, and M. Wyart, Soft Matter
      10, 5628 (2014); S. Franz, G. Parisi, P. Urbani, and F. Zamponi, Proc. Natl.
      Acad. Sci. U.S.A. 112, 14539 (2015)]. Finally, the degree of localization of the
      softest low frequency modes increases with compression, as shown by the
      participation ratio as well as their spatial configurations. Overall, our
      observations show that emulsions are marginally stable and display non-plane-wave
      modes up to vanishing frequencies.

PMID- 27886472
TI  - Stochastic Gravitational-Wave Background due to Primordial Binary Black Hole
      Mergers.
AB  - Recent Advanced LIGO detections of binary black hole mergers have prompted
      multiple studies investigating the possibility that the heavy GW150914 binary
      system was of primordial origin, and hence could be evidence for dark matter in
      the form of black holes. We compute the stochastic background arising from the
      incoherent superposition of such primordial binary black hole systems in the
      Universe and compare it to the similar background spectrum due to binary black
      hole systems of stellar origin. We investigate the possibility of detecting this
      background with future gravitational-wave detectors, and conclude that
      constraining the dark matter component in the form of black holes using
      stochastic gravitational-wave background measurements will be very challenging.

PMID- 27886473
TI  - Lifshitz Transitions in the Ferromagnetic Superconductor UCoGe.
AB  - We present high field magnetoresistance, Hall effect and thermopower measurements
      in the Ising-type ferromagnetic superconductor UCoGe. A magnetic field is applied
      along the easy magnetization c axis of the orthorhombic crystal. In the different
      experimental probes, we observed five successive anomalies at H~4, 9, 12, 16, and
      21 T. Magnetic quantum oscillations were detected both in resistivity and
      thermoelectric power. At most of the anomalies, significant changes of the
      oscillation frequencies and the effective masses have been observed, indicating
      successive Fermi surface instabilities induced by the strong magnetic
      polarization under a magnetic field.

PMID- 27886474
TI  - Vertex Corrections for Positive-Definite Spectral Functions of Simple Metals.
AB  - We present a systematic study of vertex corrections in a homogeneous electron gas
      at metallic densities. The vertex diagrams are built using a recently proposed
      positive-definite diagrammatic expansion for the spectral function. The vertex
      function not only provides corrections to the well known plasmon and particle
      hole scatterings, but also gives rise to new physical processes such as the
      generation of two plasmon excitations or the decay of the one-particle state into
      a two-particle-one-hole state. By an efficient Monte Carlo momentum integration
      we are able to show that the additional scattering channels are responsible for a
      reduction of the bandwidth, the appearance of a secondary plasmon satellite below
      the Fermi level, and a substantial redistribution of spectral weights. The
      feasibility of the approach for first-principles band-structure calculations is
      also discussed.

PMID- 27886475
TI  - Magnon Polarons in the Spin Seebeck Effect.
AB  - Sharp structures in the magnetic field-dependent spin Seebeck effect (SSE)
      voltages of Pt/Y_{3}Fe_{5}O_{12} at low temperatures are attributed to the magnon
      phonon interaction. Experimental results are well reproduced by a Boltzmann
      theory that includes magnetoelastic coupling. The SSE anomalies coincide with
      magnetic fields tuned to the threshold of magnon-polaron formation. The effect
      gives insight into the relative quality of the lattice and magnetization
      dynamics.

PMID- 27886476
TI  - Coexistence of Quantized, Time Dependent, Clusters in Globally Coupled
      Oscillators.
AB  - We report on a novel collective state, occurring in globally coupled nonidentical
      oscillators in the proximity of the point where the transition from the system's
      incoherent to coherent phase converts from explosive to continuous. In such a
      state, the oscillators form quantized clusters, where neither their phases nor
      their instantaneous frequencies are locked. The oscillators' instantaneous speeds
      are different within the clusters, but they form a characteristic cusped pattern
      and, more importantly, they behave periodically in time so that their average
      values are the same. Given its intrinsic specular nature with respect to the
      recently introduced Chimera states, the phase is termed the Bellerophon state. We
      provide an analytical and numerical description of Bellerophon states, and
      furnish practical hints on how to seek them in a variety of experimental and
      natural systems.

PMID- 27886477
TI  - Lattice Vibrations Change the Solid Solubility of an Alloy at High Temperatures.
AB  - We develop a method to accurately and efficiently determine the vibrational free
      energy as a function of temperature and volume for substitutional alloys from
      first principles. Taking Ti_{1-x}Al_{x}N alloy as a model system, we calculate
      the isostructural phase diagram by finding the global minimum of the free energy
      corresponding to the true equilibrium state of the system. We demonstrate that
      the vibrational contribution including anharmonicity and temperature dependence
      of the mixing enthalpy have a decisive impact on the calculated phase diagram of
      a Ti_{1-x}Al_{x}N alloy, lowering the maximum temperature for the miscibility gap
      from 6560 to 2860 K. Our local chemical composition measurements on thermally
      aged Ti_{0.5}Al_{0.5}N alloys agree with the calculated phase diagram.

PMID- 27886478
TI  - Quantum Entanglement as a Diagnostic of Phase Transitions in Disordered
      Fractional Quantum Hall Liquids.
AB  - We investigate the disorder-driven phase transition from a fractional quantum
      Hall state to an Anderson insulator using quantum entanglement methods. We find
      that the transition is signaled by a sharp increase in the sensitivity of a
      suitably averaged entanglement entropy with respect to disorder-the magnitude of
      its disorder derivative appears to diverge in the thermodynamic limit. We also
      study the level statistics of the entanglement spectrum as a function of
      disorder. However, unlike the dramatic phase-transition signal in the
      entanglement entropy derivative, we find a gradual reduction of level repulsion
      only deep in the Anderson insulating phase.

PMID- 27886479
TI  - Resistivity Minimum in Highly Frustrated Itinerant Magnets.
AB  - We study the transport properties of frustrated itinerant magnets comprising
      localized classical moments, which interact via exchange with the conduction
      electrons. Strong frustration stabilizes a liquidlike spin state, which extends
      down to temperatures well below the effective Ruderman-Kittel-Kasuya-Yosida
      interaction scale. The crossover into this state is characterized by spin
      structure factor enhancement at wave vectors smaller than twice the Fermi wave
      vector magnitude. The corresponding enhancement of electron scattering generates
      a resistivity upturn at decreasing temperatures.

PMID- 27886480
TI  - Floquet Realization and Signatures of One-Dimensional Anyons in an Optical
      Lattice.
AB  - We propose a simple scheme for mimicking the physics of one-dimensional anyons in
      an optical-lattice experiment. It relies on a bosonic representation of the
      anyonic Hubbard model to be realized via lattice-shaking-induced resonant
      tunneling against potential offsets, which are created by a combination of a
      lattice tilt and strong on-site interactions. No lasers additional to those used
      for the creation of the optical lattice are required. We also discuss
      experimental signatures of the continuous interpolation between bosons and
      fermions when the statistical angle theta is varied from 0 to pi. Whereas the
      real-space density of the bosonic atoms corresponds directly to that of the
      simulated anyonic model, this is not the case for the momentum distribution.
      Therefore, we propose to use Friedel oscillations in the density as a probe for
      continuous fermionization of the bosonic atoms.

PMID- 27886481
TI  - Correlation between Fragility and the Arrhenius Crossover Phenomenon in Metallic,
      Molecular, and Network Liquids.
AB  - We report the observation of a distinct correlation between the kinetic fragility
      index m and the reduced Arrhenius crossover temperature theta_{A}=T_{A}/T_{g} in
      various glass-forming liquids, identifying three distinguishable groups. In
      particular, for 11 glass-forming metallic liquids, we universally observe a
      crossover in the mean diffusion coefficient from high-temperature Arrhenius to
      low-temperature super-Arrhenius behavior at approximately theta_{A}~2 which is in
      the stable liquid phases. In contrast, for fragile molecular liquids, this
      crossover occurs at much lower theta_{A}~1.4 and usually in their supercooled
      states. The theta_{A} values for strong network liquids spans a wide range higher
      than 2. Intriguingly, the high-temperature activation barrier E_{infinity} is
      universally found to be ~11k_{B}T_{g} and uncorrelated with the fragility or the
      reduced crossover temperature theta_{A} for metallic and molecular liquids. These
      observations provide a way to estimate the low-temperature glassy characteristics
      (T_{g} and m) from the high-temperature liquid quantities (E_{infinity} and
      theta_{A}).

PMID- 27886482
TI  - Synthesis of Freestanding Graphene on SiC by a Rapid-Cooling Technique.
AB  - Graphene has a negative thermal expansion coefficient; that is, when heated, the
      graphene lattice shrinks. On the other hand, the substrates typically used for
      graphene growth, such as silicon carbide, have a positive thermal expansion
      coefficient. Hence, on cooling graphene on SiC, graphene expands but SiC shrinks.
      This mismatch will physically break the atomic bonds between graphene and SiC. We
      have demonstrated that a graphenelike buffer layer on SiC can be converted to a
      quasifreestanding monolayer graphene by a rapid-cooling treatment. The decoupling
      of graphene from the SiC substrate was actually effective for reducing the
      electric carrier scattering due to interfacial phonons. In addition, the rapidly
      cooled graphene obtained in this way was of high-quality, strain-free, thermally
      stable, and strongly hole doped. This simple, classical, but quite novel
      technique for obtaining quasifreestanding graphene could open a new path towards
      a viable graphene-based semiconductor industry.

PMID- 27886483
TI  - Photocell Optimization Using Dark State Protection.
AB  - Conventional photocells suffer a fundamental efficiency threshold imposed by the
      principle of detailed balance, reflecting the fact that good absorbers must
      necessarily also be fast emitters. This limitation can be overcome by "parking"
      the energy of an absorbed photon in a dark state which neither absorbs nor emits
      light. Here we argue that suitable dark states occur naturally as a consequence
      of the dipole-dipole interaction between two proximal optical dipoles for a wide
      range of realistic molecular dimers. We develop an intuitive model of a photocell
      comprising two light-absorbing molecules coupled to an idealized reaction center,
      showing asymmetric dimers are capable of providing a significant enhancement of
      light-to-current conversion under ambient conditions. We conclude by describing a
      road map for identifying suitable molecular dimers for demonstrating this effect
      by screening a very large set of possible candidate molecules.

PMID- 27886484
TI  - Strain Pattern in Supercooled Liquids.
AB  - Investigations of strain correlations at the glass transition reveal unexpected
      phenomena. The shear strain fluctuations show an Eshelby-strain pattern
      [~cos(4theta)/r^{2}], characteristic of elastic response, even in liquids, at
      long times. We address this using a mode-coupling theory for the strain
      fluctuations in supercooled liquids and data from both video microscopy of a two
      dimensional colloidal glass former and simulations of Brownian hard disks. We
      show that the long-ranged and long-lived strain signatures follow a scaling law
      valid close to the glass transition. For large enough viscosities, the Eshelby
      strain pattern is visible even on time scales longer than the structural
      relaxation time tau and after the shear modulus has relaxed to zero.

PMID- 27886485
TI  - Radial Acceleration Relation in Rotationally Supported Galaxies.
AB  - We report a correlation between the radial acceleration traced by rotation curves
      and that predicted by the observed distribution of baryons. The same relation is
      followed by 2693 points in 153 galaxies with very different morphologies, masses,
      sizes, and gas fractions. The correlation persists even when dark matter
      dominates. Consequently, the dark matter contribution is fully specified by that
      of the baryons. The observed scatter is small and largely dominated by
      observational uncertainties. This radial acceleration relation is tantamount to a
      natural law for rotating galaxies.

PMID- 27886486
TI  - Atom-Chip Fountain Gravimeter.
AB  - We demonstrate a quantum gravimeter by combining the advantages of an atom chip
      for the generation, delta-kick collimation, and coherent manipulation of freely
      falling Bose-Einstein condensates (BECs) with an innovative launch mechanism
      based on Bloch oscillations and double Bragg diffraction. Our high-contrast BEC
      interferometer realizes tens of milliseconds of free fall in a volume as little
      as a one centimeter cube and paves the way for measurements with sub-MUGal
      accuracies in miniaturized, robust devices.

PMID- 27886487
TI  - Onset of Superfluidity in ^{3}He Films.
AB  - We elucidate, for the first time, the overall behavior of the onset temperature
      of superfluidity in ^{3}He films for a wide range of film thicknesses d between
      0.06 and 10  MUm by taking advantage of the tunability of d implemented using
      microfabricated devices. We observe a suppression of the onset temperature of
      superfluidity T_{c}^{f} in a film from the bulk transition temperature as d
      decreases. In particular, T_{c}^{f} is strongly suppressed when d approaches the
      coherence length (~77  nm). The observed T_{c}^{f} as a function of d is similar
      to that expected from the quasiclassical theory, but it unexpectedly deviates
      from the theoretical value by several percent when 0.5?d?5  MUm.

PMID- 27886488
TI  - Skyrmions at the Edge: Confinement Effects in Fe/Ir(111).
AB  - We have employed spin-polarized scanning tunneling microscopy and Monte Carlo
      simulations to investigate the effect of lateral confinement onto the nano
      Skyrmion lattice in Fe/Ir(111). We find a strong coupling of one diagonal of the
      square magnetic unit cell to the close-packed edges of Fe nanostructures. In
      triangular islands this coupling in combination with the mismatching symmetries
      of the islands and of the square nano-Skyrmion lattice leads to frustration and
      triple-domain states. In direct vicinity to ferromagnetic NiFe islands, the
      surrounding Skyrmion lattice forms additional domains. In this case a side of the
      square magnetic unit cell prefers a parallel orientation to the ferromagnetic
      edge. These experimental findings can be reproduced and explained by Monte Carlo
      simulations. Here, the single-domain state of a triangular island is lower in
      energy, but nevertheless multidomain states occur due to the combined effect of
      entropy and an intrinsic domain wall pinning arising from the skyrmionic
      character of the spin texture.

PMID- 27886489
TI  - Droplets of Trapped Quantum Dipolar Bosons.
AB  - Strongly interacting systems of dipolar bosons in three dimensions confined by
      harmonic traps are analyzed using the exact path integral ground-state Monte
      Carlo method. By adding a repulsive two-body potential, we find a narrow window
      of interaction parameters leading to stable ground-state configurations of
      droplets in a crystalline arrangement. We find that this effect is entirely due
      to the interaction present in the Hamiltonian without resorting to additional
      stabilizing mechanisms or specific three-body forces. We analyze the number of
      droplets formed in terms of the Hamiltonian parameters, relate them to the
      corresponding s-wave scattering length, and discuss a simple scaling model for
      the density profiles. Our results are in qualitative agreement with recent
      experiments showing a quantum Rosensweig instability in trapped Dy atoms.

PMID- 27886490
TI  - Dynamic Scaling and Island Growth Kinetics in Pulsed Laser Deposition of
      SrTiO_{3}.
AB  - We use real-time diffuse surface x-ray diffraction to probe the evolution of
      island size distributions and its effects on surface smoothing in pulsed laser
      deposition (PLD) of SrTiO_{3}. We show that the island size evolution obeys
      dynamic scaling and two distinct regimes of island growth kinetics. Our data show
      that PLD film growth can persist without roughening despite thermally driven
      Ostwald ripening, the main mechanism for surface smoothing, being shut down. The
      absence of roughening is concomitant with decreasing island density,
      contradicting the prevailing view that increasing island density is the key to
      surface smoothing in PLD. We also report a previously unobserved crossover from
      diffusion-limited to attachment-limited island growth that reveals the influence
      of nonequilibrium atomic level surface transport processes on the growth modes in
      PLD. We show by direct measurements that attachment-limited island growth is the
      dominant process in PLD that creates step flowlike behavior or quasistep flow as
      PLD "self-organizes" local step flow on a length scale consistent with the
      substrate temperature and PLD parameters.

PMID- 27886491
TI  - Interplay of Site and Bond Electron-Phonon Coupling in One Dimension.
AB  - The interplay of bond and charge correlations is studied in a one-dimensional
      model with both Holstein and Su-Schrieffer-Heeger (SSH) couplings to quantum
      phonons. The problem is solved exactly by quantum Monte Carlo simulations. If one
      of the couplings dominates, the ground state is a Peierls insulator with long
      range bond or charge order. At weak coupling, the results suggest a spin-gapped
      and repulsive metallic phase arising from the competing order parameters and
      lattice fluctuations. Such a phase is absent from the pure SSH model even for
      quantum phonons. At strong coupling, evidence for a continuous transition between
      the two Peierls states is presented.

PMID- 27886493
TI  - Erasure without Work in an Asymmetric Double-Well Potential.
AB  - According to Landauer's principle, erasing a memory requires an average work of
      at least kTln2 per bit. Recent experiments have confirmed this prediction for a
      one-bit memory represented by a symmetric double-well potential. Here, we present
      an experimental study of erasure for a memory encoded in an asymmetric double
      well potential. Using a feedback trap, we find that the average work to erase can
      be less than kTln2. Surprisingly, erasure protocols that differ subtly give
      measurably different values for the asymptotic work, a result we explain by
      showing that one protocol is symmetric with the respect to time reversal, while
      the other is not. The differences between the protocols help clarify the
      distinctions between thermodynamic and logical reversibility.

PMID- 27886492
TI  - Role of Excited States In High-order Harmonic Generation.
AB  - We investigate the role of excited states in high-order harmonic generation by
      studying the spectral, spatial, and temporal characteristics of the radiation
      produced near the ionization threshold of argon by few-cycle laser pulses. We
      show that the population of excited states can lead either to direct extreme
      ultraviolet emission through free induction decay or to the generation of high
      order harmonics through ionization from these states and recombination to the
      ground state. By using the attosecond lighthouse technique, we demonstrate that
      the high-harmonic emission from excited states is temporally delayed by a few
      femtoseconds compared to the usual harmonics, leading to a strong nonadiabatic
      spectral redshift.

PMID- 27886494
TI  - Stochastic Predator-Prey Dynamics of Transposons in the Human Genome.
AB  - Transposable elements, or transposons, are DNA sequences that can jump from site
      to site in the genome during the life cycle of a cell, usually encoding the very
      enzymes which perform their excision. However, some transposons are parasitic,
      relying on the enzymes produced by the regular transposons. In this case, we show
      that a stochastic model, which takes into account the small copy numbers of the
      active transposons in a cell, predicts noise-induced predator-prey oscillations
      with a characteristic time scale that is much longer than the cell replication
      time, indicating that the state of the predator-prey oscillator is stored in the
      genome and transmitted to successive generations. Our work demonstrates the
      important role of the number fluctuations in the expression of mobile genetic
      elements, and shows explicitly how ecological concepts can be applied to the
      dynamics and fluctuations of living genomes.

PMID- 27886495
TI  - New Integrable 4D Quantum Field Theories from Strongly Deformed Planar N=4
      Supersymmetric Yang-Mills Theory.
AB  - We introduce a family of new integrable quantum field theories in four dimensions
      by considering the gamma-deformed N=4 supersymmetric Yang-Mills (SYM) theory in
      the double scaling limit of large imaginary twists and small coupling. This limit
      discards the gauge fields and retains only certain Yukawa and scalar interactions
      with three arbitrary effective couplings. In the 't Hooft limit, these 4D
      theories are integrable, and contain a wealth of conformal correlators such that
      the whole arsenal of AdS/CFT integrability remains applicable. As a special case
      of these models, we obtain a quantum field theory of two complex scalars with a
      chiral, quartic interaction. The Berenstein-Maldacena-Nastase vacuum anomalous
      dimension is dominated in each loop order by a single "wheel" graph, whose bulk
      represents an integrable "fishnet" graph. This explicitly demonstrates the all
      loop integrability of gamma-deformed planar N=4 SYM theory, at least in our
      limit. Using this feature and integrability results we provide an explicit
      conjecture for the periods of double-wheel graphs with an arbitrary number of
      spokes in terms of multiple zeta values of limited depth.

PMID- 27886496
TI  - Nonequilibrium Phase Behavior from Minimization of Free Power Dissipation.
AB  - We develop a general theory for describing phase coexistence between
      nonequilibrium steady states in Brownian systems, based on power functional
      theory [M. Schmidt and J. M. Brader, J. Chem. Phys. 138, 214101 (2013)]. We apply
      the framework to the special case of fluid-fluid phase separation of active soft
      sphere swimmers. The central object of the theory, the dissipated free power, is
      calculated via computer simulations and compared to a simple analytical
      approximation. The theory describes well the simulation data and predicts
      motility-induced phase separation due to avoidance of dissipative clusters.

PMID- 27886497
TI  - Large Cross-Phase Modulations at the Few-Photon Level.
AB  - We demonstrate an efficient cross-phase modulation (XPM) based on a closed-loop
      double-Lambda system. The property of the double-Lambda medium can be controlled
      by changing the phases of the applied optical fields. This phase-dependent XPM
      scheme can achieve large phase modulations at low-light intensities without
      requiring cavities or tightly focusing laser beams. With this scheme, we observe
      a pi-level phase shift with two pulses, both consisting of eight photons in cold
      rubidium atoms. Such a novel scheme provides a simple route to generate strong
      interactions between photons and may have potential applications in all-optical
      quantum signal processing.

PMID- 27886498
TI  - Well-Ordered In Adatoms at the In_{2}O_{3}(111) Surface Created by Fe Deposition.
AB  - Metal deposition on oxide surfaces usually results in adatoms, clusters, or
      islands of the deposited material, where defects in the surface often act as
      nucleation centers. Here an alternate configuration is reported. After the vapor
      deposition of Fe on the In_{2}O_{3}(111) surface at room temperature, ordered
      adatoms are observed with scanning tunneling microscopy. These are identical to
      the In adatoms that form when the sample is reduced by heating in ultrahigh
      vacuum. Density functional theory calculations confirm that Fe interchanges with
      In in the topmost layer, pushing the excess In atoms to the surface where they
      arrange as a well-ordered adatom array.

PMID- 27886499
TI  - Interacting Atomic Interferometry for Rotation Sensing Approaching the Heisenberg
      Limit.
AB  - Atom interferometers provide exquisite measurements of the properties of
      noninertial frames. While atomic interactions are typically detrimental to good
      sensing, efforts to harness entanglement to improve sensitivity remain
      tantalizing. Here we explore the role of interactions in an analogy between
      atomic gyroscopes and SQUIDs, motivated by recent experiments realizing ring
      shaped traps for ultracold atoms. We explore the one-dimensional limit of these
      ring systems with a moving weak barrier, such as that provided by a blue-detuned
      laser beam. In this limit, we employ Luttinger liquid theory and find an analogy
      with the superconducting phase-slip qubit, in which the topological charge
      associated with persistent currents can be put into superposition. In particular,
      we find that strongly interacting atoms in such a system could be used for
      precision rotation sensing. We compare the performance of this new sensor to an
      equivalent noninteracting atom interferometer, and find improvements in
      sensitivity and bandwidth beyond the atomic shot-noise limit.

PMID- 27886500
TI  - Publisher's Note: Limits on Active to Sterile Neutrino Oscillations from
      Disappearance Searches in the MINOS, Daya Bay, and Bugey-3 Experiments [Phys.
      Rev. Lett. 117, 151801 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.151801.

PMID- 27886501
TI  - Fate of Alpha Dynamos at Large Rm.
AB  - At the heart of today's solar magnetic field evolution models lies the alpha
      dynamo description. In this work, we investigate the fate of alpha dynamos as the
      magnetic Reynolds number Rm is increased. Using Floquet theory, we are able to
      precisely quantify mean-field effects like the alpha and beta effect (i) by
      rigorously distinguishing dynamo modes that involve large-scale components from
      the ones that only involve small scales, and by (ii) providing a way to
      investigate arbitrary large-scale separations with minimal computational cost. We
      apply this framework to helical and nonhelical flows as well as to random flows
      with short correlation time. Our results determine that the alpha description is
      valid for Rm smaller than a critical value Rm_{c} at which small-scale dynamo
      instability starts. When Rm is above Rm_{c}, the dynamo ceases to follow the mean
      field description and the growth rate of the large-scale modes becomes
      independent of the scale separation, while the energy in the large-scale modes is
      inversely proportional to the square of the scale separation. The results in this
      second regime do not depend on the presence of helicity. Thus, alpha-type
      modeling for solar and stellar models needs to be reevaluated and new directions
      for mean-field modeling are proposed.

PMID- 27886502
TI  - Topological Surface States in Dense Solid Hydrogen.
AB  - Metallization of dense hydrogen and associated possible high-temperature
      superconductivity represents one of the key problems of physics. Recent
      theoretical studies indicate that before becoming a good metal, compressed solid
      hydrogen passes through a semimetallic stage. We show that such semimetallic
      phases predicted to be the most stable at multimegabar (~300  GPa) pressures are
      not conventional semimetals: they exhibit topological metallic surface states
      inside the bulk "direct" gap in the two-dimensional surface Brillouin zone; that
      is, metallic surfaces may appear even when the bulk of the material remains
      insulating. Examples include hydrogen in the Cmca-12 and Cmca-4 structures; Pbcn
      hydrogen also has metallic surface states but they are of a nontopological
      nature. The results provide predictions for future measurements, including probes
      of possible surface superconductivity in dense hydrogen.

PMID- 27886503
TI  - Signatures of Hyperfine, Spin-Orbit, and Decoherence Effects in a Pauli Spin
      Blockade.
AB  - We detect in real time interdot tunneling events in a weakly coupled two-electron
      double quantum dot in GaAs. At finite magnetic fields, we observe two
      characteristic tunneling times T_{d} and T_{b}, belonging to, respectively, a
      direct and a blocked (spin-flip-assisted) tunneling. The latter corresponds to
      the lifting of a Pauli spin blockade, and the tunneling times ratio
      eta=T_{b}/T_{d} characterizes the blockade efficiency. We find pronounced changes
      in the behavior of eta upon increasing the magnetic field, with eta increasing,
      saturating, and increasing again. We explain this behavior as due to the
      crossover of the dominant blockade-lifting mechanism from the hyperfine to spin
      orbit interactions and due to a change in the contribution of the charge
      decoherence.

PMID- 27886505
TI  - Dimensional Hierarchy of Fermionic Interacting Topological Phases.
AB  - We present a dimensional reduction argument to derive the classification
      reduction of fermionic symmetry protected topological phases in the presence of
      interactions. The dimensional reduction proceeds by relating the topological
      character of a d-dimensional system to the number of zero-energy bound states
      localized at zero-dimensional topological defects present at its surface. This
      correspondence leads to a general condition for symmetry preserving interactions
      that render the system topologically trivial, and allows us to explicitly write a
      quartic interaction to this end. Our reduction shows that all phases with
      topological invariant smaller than n are topologically distinct, thereby reducing
      the noninteracting Z classification to Z_{n}.

PMID- 27886504
TI  - Controlling Rayleigh-Taylor Instabilities in Magnetically Driven Solid Metal
      Shells by Means of a Dynamic Screw Pinch.
AB  - Magnetically driven implosions of solid metal shells are an effective vehicle to
      compress materials to extreme pressures and densities. Rayleigh-Taylor
      instabilities (RTI) are ubiquitous, yet typically undesired features in all such
      experiments where solid materials are rapidly accelerated to high velocities. In
      cylindrical shells ("liners"), the magnetic field driving the implosion can
      exacerbate the RTI. We suggest an approach to implode solid metal liners enabling
      a remarkable reduction in the growth of magnetized RTI (MRTI) by employing a
      magnetic drive with a tilted, dynamic polarization, forming a dynamic screw
      pinch. Our calculations, based on a self-consistent analytic framework,
      demonstrate that the cumulative growth of the most deleterious MRTI modes may be
      reduced by as much as 1 to 2 orders of magnitude. One key application of this
      technique is to generate increasingly stable, higher-performance implosions of
      solid metal liners to achieve fusion [M. R. Gomez et al., Phys. Rev. Lett. 113,
      155003 (2014)]. We weigh the potentially dramatic benefits of the solid liner
      dynamic screw pinch against the experimental tradeoffs required to achieve the
      desired drive field history and identify promising designs for future
      experimental and computational studies.

PMID- 27886507
TI  - Local Density of States for Nanoplasmonics.
AB  - We obtain the local density of states (LDOS) for any nanoplasmonic system in the
      frequency range dominated by a localized surface plasmon. By including the Ohmic
      losses in a consistent way, we show that the plasmon LDOS is proportional to the
      local field intensity normalized by the absorbed power. We obtain explicit
      formulas for the energy transfer (ET) between quantum emitters and plasmons as
      well as between donors and acceptors situated near a plasmonic structure. In the
      latter case, we find that the plasmon-assisted ET rate is proportional to the
      LDOS product at the donor and acceptor positions, obtain, in a general form, the
      plasmon ET enhancement factor, and establish the transition onset between Forster
      dominated and plasmon-dominated ET regimes.

PMID- 27886508
TI  - Immunization and Targeted Destruction of Networks using Explosive Percolation.
AB  - A new method ("explosive immunization") is proposed for immunization and targeted
      destruction of networks. It combines the explosive percolation (EP) paradigm with
      the idea of maintaining a fragmented distribution of clusters. The ability of
      each node to block the spread of an infection (or to prevent the existence of a
      large cluster of connected nodes) is estimated by a score. The algorithm proceeds
      by first identifying low score nodes that should not be vaccinated or destroyed,
      analogously to the links selected in EP if they do not lead to large clusters. As
      in EP, this is done by selecting the worst node (weakest blocker) from a finite
      set of randomly chosen "candidates." Tests on several real-world and model
      networks suggest that the method is more efficient and faster than any existing
      immunization strategy. Because of the latter property it can deal with very large
      networks.

PMID- 27886509
TI  - Smooth Horizonless Geometries Deep Inside the Black-Hole Regime.
AB  - We construct the first family of horizonless supergravity solutions that have the
      same mass, charges, and angular momenta as general supersymmetric rotating D1-D5
      P black holes in five dimensions. This family includes solutions with arbitrarily
      small angular momenta, deep within the regime of quantum numbers and couplings
      for which a large classical black hole exists. These geometries are well
      approximated by the black-hole solution, and in particular exhibit the same near
      horizon throat. Deep in this throat, the black-hole singularity is resolved into
      a smooth cap. We also identify the holographically dual states in the N=(4,4) D1
      D5 orbifold conformal field theory (CFT). Our solutions are among the states
      counted by the CFT elliptic genus, and provide examples of smooth microstate
      geometries within the ensemble of supersymmetric black-hole microstates.

PMID- 27886510
TI  - Generation of Subterahertz Superradiance Pulses Based on Excitation of a Surface
      Wave by Relativistic Electron Bunches Moving in Oversized Corrugated Waveguides.
AB  - The first experiments on the observation of short pulsed superradiant (SR)
      emission with the excitation of a surface wave by a relativistic electron bunch
      moving in an oversized corrugated waveguide were performed. Subterahertz SR
      pulses with a central frequency of 0.14 THz, an ultrashort duration of 150 ps,
      and an extremely high peak power of 50-70 MW were generated. The experiments were
      based on a theoretical consideration including the quasioptical approach and
      direct particle-in-cell simulations.

PMID- 27886511
TI  - Theory of Spin Loss at Metallic Interfaces.
AB  - Interfacial spin-flip scattering plays an important role in magnetoelectronic
      devices. Spin loss at metallic interfaces is usually quantified by matching the
      magnetoresistance data for multilayers to the Valet-Fert model, while treating
      each interface as a fictitious bulk layer whose thickness is delta times the spin
      diffusion length. By employing the properly generalized circuit theory and the
      scattering matrix approaches, we derive the relation of the parameter delta to
      the spin-flip transmission and reflection probabilities at an individual
      interface. It is found that delta is proportional to the square root of the
      probability of spin-flip scattering. We calculate the spin-flip scattering
      probabilities for flat and rough Cu/Pd interfaces using the Landauer-Buttiker
      method based on the first-principles electronic structure and find delta to be in
      reasonable agreement with experiment.

PMID- 27886506
TI  - Measurement of Excitation Spectra in the ^{12}C(p,d) Reaction near the eta^{'}
      Emission Threshold.
AB  - Excitation spectra of ^{11}C are measured in the ^{12}C(p,d) reaction near the
      eta^{'} emission threshold. A proton beam extracted from the synchrotron SIS-18
      at GSI with an incident energy of 2.5 GeV impinges on a carbon target. The
      momenta of deuterons emitted at 0 degrees  are precisely measured with the
      fragment separator (FRS) operated as a spectrometer. In contrast to theoretical
      predictions on the possible existence of deeply bound eta^{'}-mesic states in
      carbon nuclei, no distinct structures are observed associated with the formation
      of bound states. The spectra are analyzed to set stringent constraints on the
      formation cross section and on the hitherto barely known eta^{'}-nucleus
      interaction.

PMID- 27886512
TI  - Angular Dynamics of a Small Particle in Turbulence.
AB  - We compute the angular dynamics of a neutrally buoyant nearly spherical particle
      immersed in an unsteady fluid. We assume that the particle is small, that its
      translational slip velocity is negligible, and that unsteady and convective
      inertia are small perturbations. We derive an approximation for the torque on the
      particle that determines the first inertial corrections to Jeffery's equation.
      These corrections arise as a consequence of local vortex stretching and can be
      substantial in turbulence, where local vortex stretching is strong and closely
      linked to the irreversibility of turbulence.

PMID- 27886513
TI  - A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in
      Obese Women.
AB  - Obesity in reproductive-aged women is associated with a shorter luteal phase and
      lower progesterone levels. Lipid accumulation in follicles of obese women
      compromises endoplasmic reticulum (ER) function, activating ER stress in
      granulosa cells. We hypothesized that ER stress activation in granulosa-lutein
      cells (GLCs) would modulate progesterone production and contribute to obesity
      associated progesterone deficiency. Pretreatment with an ER stress inducer,
      tunicamycin or thapsigargin, inhibited human chorionic gonadotropin (hCG)
      stimulated progesterone production in cultured human GLCs. Pretreatment of human
      GLCs with tunicamycin inhibited hCG-stimulated expression of steroidogenic acute
      regulatory protein (StAR) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD)
      messenger RNAs (mRNAs) without affecting expression of cytochrome P450
      cholesterol side-chain cleavage enzyme (P450scc), as determined by real-time
      quantitative polymerase chain reaction. Pretreatment with tunicamycin also
      inhibited hCG-stimulated expression of StAR protein and 3beta-HSD enzyme activity
      in cultured human GLCs, as determined by Western blot analysis and an enzyme
      immunoassay, respectively, but did not affect hCG-induced intracellular 3',5'
      cyclic adenosine monophosphate accumulation. Furthermore, tunicamycin attenuated
      hCG-induced protein kinase A and extracellular signal-regulated kinase
      activation, as determined by Western blot analysis. In vivo administration of
      tunicamycin to pregnant mare serum gonadotropin-treated immature mice prior to
      hCG treatment inhibited the hCG-stimulated increase in serum progesterone levels
      and hCG-induced expression of StAR and 3beta-HSD mRNA in the ovary without
      affecting serum estradiol levels or the number of corpora lutea. Our findings
      indicate that ER stress in the follicles of obese women contributes to
      progesterone deficiency by inhibiting hCG-induced progesterone production in
      granulosa cells.

PMID- 27886514
TI  - Sugar-based novel niosomal nanocarrier system for enhanced oral bioavailability
      of levofloxacin.
AB  - CONTEXT: Vesicular systems have attracted great attention in drug delivery
      because of their amphiphilicity, biodegradability, non-toxicity and potential for
      increasing drug bioavailability. OBJECTIVE: A novel sugar-based double-tailed
      surfactant containing renewable block was synthesized for preparing niosomal
      vesicles that could be exploited for Levofloxacin encapsulation, aiming to
      increase its oral bioavailability. MATERIALS AND METHODS: The surfactant was
      characterized by 1H NMR, mass spectroscopy and Fourier transform infrared
      spectroscopy (FT-IR). Its biocompatibility was studied against cell cultures and
      human blood hemolysis. In vivo acute toxicity was evaluated in mice. The vesicle
      morphology, size, drug-excipients interaction and entrapment efficiency (EE) were
      examined using atomic force microscope (AFM), dynamic light scattering (DLS), FT
      IR and HPLC. Oral bioavailability studies of Levofloxacin in surfactant-based
      niosomal formulation were carried out using rabbits and plasma samples were
      analyzed using HPLC. RESULTS AND DISCUSSION: Vesicles were spherical in shape and
      the size was 190.31 +/- 4.51 nm with a polydispersity index (PDI) of 0.29 +/-
      0.03. The drug EE in niosomes was 68.28 +/- 3.45%. When applied on cell lines,
      high cell viability was observed even after prolonged exposure at high
      concentrations. It caused 5.77 +/- 1.34% hemolysis at 1000 MUg/mL and was found
      to be safe up to 2000 mg/kg. Elevated Levofloxacin plasma concentration was
      achieved when delivered with novel vesicles. CONCLUSION: The surfactant was
      demonstrated to be safe and effective as carrier of Levofloxacin. The study
      suggests that this sugar-based double-tailed nonionic surfactant could be
      promising nano-vesicular system for delivery and enhancing oral bioavailability
      of the hydrophobic Levofloxacin.

PMID- 27886515
TI  - Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely
      Regulate Bioactive Lipid Production?
AB  - Context: Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical
      features of an endocrine/metabolic disorder, including hyperinsulinemia and
      hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both
      tightly linked to PCOS and obesity, play important roles in inflammation and
      reproduction. Objective: This study aimed to investigate serum lipid profiles in
      newly diagnosed patients with PCOS using lipidomics and correlate these features
      with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity.
      Design and Setting: Thirty-two newly diagnosed women with PCOS and 34 controls
      were divided into obese and lean subgroups. A PCOS rat model was used to validate
      results of the human studies. Main Outcome Measures: Serum lipid profiles,
      including phospholipids, free fatty acids (FFAs), and bioactive lipids, were
      analyzed using gas chromatography-mass spectrometry (MS) and liquid
      chromatography-MS. Results: Elevation in phosphatidylcholine and a concomitant
      decrease in lysophospholipid were found in obese patients with PCOS vs lean
      controls. Obese patients with PCOS had decreased PUFA levels and increased levels
      of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids
      downstream of arachidonic acid were increased in obese controls, but reduced in
      both obese and lean patients with PCOS vs their respective controls. Conclusions:
      Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA
      metabolites. Circulating insulin and androgens may have opposing effects on lipid
      profiles in patients with PCOS, particularly on the bioactive lipid metabolites
      derived from PUFAs. These clinical observations warrant further studies of the
      molecular mechanisms and clinical implications of PCOS and obesity.

PMID- 27886517
TI  - Organic vs. functional neurological disorders: The role of childhood
      psychological trauma.
AB  - Although the relationship between psychological trauma and medically unexplained
      symptoms (MUS) is well established, this relationship is less well understood in
      people with medically unexplained neurological symptoms. In the present study, we
      set out to compare people with functional neurological disorders, and organic
      neurological disorders, in terms of childhood and adulthood traumatic events,
      traumatic stress, emotional dysregulation and symptoms of depression and anxiety.
      We have hypothesised that those with functional neurological disorders would be
      more likely to report childhood and adulthood traumatic life events, traumatic
      symptomatology, emotional dysregulation and symptoms of anxiety and depression,
      compared to those with organic neurological disorders. Sample consisted of a
      consecutive series of people with functional neurological disorders and with
      organic neurological disorders (n=82) recruited from a hospital in Scotland.
      Participants completed measures of life events, traumatic stress, emotional
      regulation, anxiety and depression. The two groups were found to significantly
      differ in relation to all measures, with the MUS group being more likely to
      report childhood and adulthood life events, more severe emotional dysregulation,
      traumatic stress and symptoms of anxiety and stress. Logistic regression analysis
      revealed that exposure to childhood traumatic life events, specifically childhood
      sexual abuse, and childhood physical neglect, were the only factors which were
      significantly associated with membership of the medically unexplained
      neurological symptoms group. Although further research is required to confirm our
      findings, our results suggest that identifying and addressing the impact of
      childhood trauma, may alleviate distress and aid recovery from functional
      neurological disorders.

PMID- 27886516
TI  - Inflammatory Stimuli Increase Progesterone Receptor-A Stability and
      Transrepressive Activity in Myometrial Cells.
AB  - The steroid hormone progesterone acting via the nuclear progesterone receptor
      (PR) isoforms, progesterone receptor A (PR-A) and progesterone receptor B (PR-B),
      is essential for the maintenance of uterine quiescence during pregnancy.
      Inhibition of PR signaling augments uterine contractility and induces labor.
      Human parturition is thought to be triggered by modulation of PR signaling in
      myometrial cells to induce a functional progesterone withdrawal. One mechanism
      for functional progesterone withdrawal is increased abundance of PR-A, which
      decreases progesterone responsiveness by inhibiting the transcriptional activity
      of PR-B. Human parturition also involves tissue-level inflammation within the
      myometrium. This study examined the control of PR-A abundance and transrepressive
      activity in myometrial cells and the role of the inflammatory stimuli in the form
      of interleukin-1beta (IL-1beta) and lipopolysaccharide (LPS) in these processes.
      We found that abundance of PR-A was markedly increased by progesterone and by
      exposure to IL-1beta and LPS via posttranslational mechanisms involving increased
      PR-A protein stability. In contrast, progesterone decreased abundance of PR-B by
      increasing its rate of degradation. Together, progesterone and proinflammatory
      stimuli induced a PR-A-dominant state in myometrial cells similar to that
      observed in term laboring myometrium. IL-1beta and LPS also increased the
      capacity for PR-A to inhibit the transcriptional activity of PR-B. Taken
      together, our data suggest that proinflammatory stimuli increase the steady-state
      levels of PR-A and its transrepressive activity in myometrial cells and support
      the hypothesis that tissue-level inflammation triggers parturition by inducing PR
      A-mediated functional progesterone withdrawal.

PMID- 27886518
TI  - Maltreatment, family environment, and social risk factors: Determinants of the
      child welfare to juvenile justice transition among maltreated children and
      adolescents.
AB  - This study prospectively examines the transition from the child welfare system
      into the juvenile justice system among 10,850 maltreated children and adolescents
      and explores how patterns of risks, including severity and chronicity of
      maltreatment, adverse family environment, and social risk factors, affect service
      systems transition. Almost three percent of maltreated children and adolescents
      had their first juvenile justice adjudication within an average of approximately
      six years of their initial child protective services investigation (CPS). Social
      risk factors, including a child's age at index CPS investigation (older), gender
      (boys), and race/ethnicity (Black and Hispanic) significantly predicted the risk
      of transition into the juvenile justice system. Recurrence of maltreatment and
      experiencing at least one incident of neglect over the course of the study period
      also increased the risk of transition into the juvenile justice system. However,
      subtypes of maltreatment, including physical, sexual, and other types of abuse
      did not significantly predict the risk of juvenile justice system transition.
      Finally, family environment characterized by poverty also significantly increased
      the risk of juvenile justice system transition. These findings have important
      implications for developing and tailoring services for maltreated children,
      particularly those at-risk for transitioning into the juvenile justice system.

PMID- 27886520
TI  - Surprise! 20-month-old infants understand the emotional consequences of false
      beliefs.
AB  - Recent studies suggest that by the second year of life, infants can attribute
      false beliefs to agents. However, prior studies have largely focused on infants'
      ability to predict a mistaken agent's physical actions on objects. The present
      research investigated whether 20-month-old infants could also reason about belief
      based emotional displays. In Experiments 1 and 2, infants viewed an agent who
      shook two objects: one rattled and the other was silent. Infants expected the
      agent to express surprise at the silent object if she had a false belief that
      both objects rattled, but not if she was merely ignorant about the objects'
      properties. Experiment 3 replicated and extended these findings: if an agent
      falsely believed that two containers held toy bears (when only one did so),
      infants expected the agent to express surprise at the empty, but not the full,
      container. Together, these results provide the first evidence that infants in the
      second year of life understand the causal relationship between beliefs and
      emotional displays. These findings thus provide new evidence for false-belief
      understanding in infancy and suggest that infants, like older children, possess a
      robust understanding of belief that applies to a broad range of belief-based
      responses.

PMID- 27886519
TI  - Mind wandering and the attention network system.
AB  - Attention and mind wandering are often seen as anticorrelated. However, both
      attention and mind wandering are multi-component processes, and their
      relationship may be more complex than previously thought. In this study, we
      tested the interference of different types of thoughts as measured by a Thought
      Identification Task - TIT (on task thoughts, task related interference thoughts,
      external distractions, stimulus independent and task unrelated thoughts) on
      different components of the attention network system - ANT (alerting, orienting,
      executive). Results show that, during the ANT, individuals were predominantly
      involved in task related interference thoughts which, along with external
      distractors, significantly impaired their performance accuracy. However, mind
      wandering (i.e., stimulus independent and task unrelated thoughts) did not
      significantly interfere with accuracy in the ANT. No significant relationship was
      found between type of thoughts and alerting, orienting, or executive effects in
      the ANT. While task related interference thoughts and external distractions
      seemed to impair performance on the attention task, mind wandering was still
      compatible with satisfactory performance in the ANT. The present results
      confirmed the importance of differentiating type of "out of task" thoughts in
      studying the relationship between though distractors and attention.

PMID- 27886521
TI  - Seeing the world through others' minds: Inferring social context from behaviour.
AB  - Past research tells us that individuals can infer information about a target's
      emotional state and intentions from their facial expressions (Frith & Frith,
      2012), a process known as mentalising. This extends to inferring the events that
      caused the facial reaction (e.g. Pillai, Sheppard, & Mitchell, 2012; Pillai et
      al., 2014), an ability known as retrodictive mindreading. Here, we enter new
      territory by investigating whether or not people (perceivers) can guess a
      target's social context by observing their response to stimuli. In Experiment 1,
      perceivers viewed targets' responses and were able to determine whether these
      targets were alone or observed by another person. In Experiment 2, another group
      of perceivers, without any knowledge of the social context or what the targets
      were watching, judged whether targets were hiding or exaggerating their facial
      expressions; and their judgments discriminated between conditions in which
      targets were observed and alone. Experiment 3 established that another group of
      perceivers' judgments of social context were associated with estimations of
      target expressivity to some degree. In Experiments 1 and 2, the eye movements of
      perceivers also varied between conditions in which targets were observed and
      alone. Perceivers were thus able to infer a target's social context from their
      visible response. The results demonstrate an ability to use other minds as a
      window onto a social context that could not be seen directly.

PMID- 27886522
TI  - Increase in PAS-induced neuroplasticity after a treatment course of intranasal
      ketamine for depression. Report of three cases from a placebo-controlled trial.
AB  - BACKGROUND: Animal studies suggest that neural plasticity may play a role in the
      antidepressant effects of a single ketamine dose. However, the potential effects
      of repeated ketamine treatments on human neuroplasticity are unknown. METHODS:
      This pilot RCT study measured plasticity-induced changes before and after a
      ketamine course, in three treatment-resistant depressed subjects, who were
      randomized to receive 8 intranasal treatments of 100mg ketamine or 4.5mg
      midazolam. Mood ratings were performed by a trained blinded rater at baseline and
      24h-48h after the ketamine course, using the Montgomery Asberg Depression Rating
      Scale (MADRS). Neuroplasticity was assessed in the motor cortex using a paired
      associative stimulation (PAS) paradigm at baseline and 24h-48h after the
      treatment course. No changes in current psychotropic medication or dosage were
      permitted for 4weeks prior to trial entry and throughout the trial. RESULTS: The
      subject receiving ketamine, but not those receiving midazolam, presented a marked
      increase in neural plasticity after the treatment course. However, mood changes
      were not associated with changes in neural plasticity. LIMITATIONS: Pilot study
      with small sample size. Concomitant antidepressant medications taken. Plasticity
      was tested in the motor cortex only, thus the generalizability of these findings
      to other brain areas cannot be assumed. CONCLUSIONS: These results suggest that a
      course of intranasal ketamine may enhance synaptic plasticity in subjects with
      depression, but this was not associated with antidepressant effects. Further
      research on this topic is warranted.

PMID- 27886523
TI  - Two years follow up of 270 patients treated by transvaginal mesh for anterior
      and/or apical prolapse.
AB  - OBJECTIVE: The aim of this study was to assess the 1 and 2 years outcomes of
      transvaginal single incision mesh surgery (SIMS) for anterior pelvic organ
      prolapse (POP). MATERIAL AND METHODS: This was a prospective study including all
      patients from November 2008 to December 2012 who underwent SIMS for symptomatic
      anterior prolapse stage>=2, according to the POP Quantification (POP-Q). Symptoms
      and quality of life were assessed using validated questionnaires: Pelvic Floor
      Distress Inventory (PFDI-20), Pelvic Floor Impact questionnaire (PFIQ-7), and
      Prolapse/Incontinence Sexual Questionnaire (PISQ-12). The main outcome was
      subjective success (question 3 of PFDI-20 score=0). Safety, anatomic and
      functional outcomes were used as the secondary outcomes. RESULTS: A total of 270
      patients were included in the study. Subjective success rate was 95,4% and 92,2%
      at 1 and 2 years. Objective success rate was 65,9%and 60,5% at 1 and 2 years. At
      1year, composite failure (subjective+objective) occurred for 11 patients (4,6%),
      5 patients with direct recurrence and 6 with indirect recurrence. At 2 years,
      composite failure was reported for 14 patients (6,4%): 6 direct recurrences and 8
      indirect recurrences. Re-treatment was performed in one case (0,4%). One case
      (0,4%) of asymptomatic mesh exposure occurred. The reoperation rate for mesh
      related complications was 3%. We reported a de novo dyspareunia rate of 8,4%,
      5,3% considered as mesh-related. A significant improvement was noted for symptoms
      and quality of life. CONCLUSION: POP repair using SIMS is a safe and efficient
      treatment of anterior compartment prolapse in the medium term with a low rate of
      mesh-related complications. Longer-term follow-up is ongoing.

PMID- 27886525
TI  - Development and assays estradiol equivalent concentration from prawn (p-EEQ) in
      river prawn, Macrobrachium nipponense, in Taiwan.
AB  - The present study established a fast and convenient bioassay method for aqueous
      ecosystems using the prawn estradiol equivalent concentration (p-EEQ) of male
      Macrobrachium nipponense, which produce vitellogenin (VTG) after exposure to xeno
      estrogens. This method was then used to determine the concentrations of xeno
      estrogen pollutants in the rivers of Taiwan. To establish the calibration curve
      for the concentrations based on the p-EEQ, the induced VTG content was determined
      using the alkali-labile phosphate method after male M. nipponense were exposed to
      0, 10, 100, 1,000 and 10,000ng/L of 17beta-estradiol for 1, 3, 5, 7, 10 and 14
      days, respectively. The results of the experiments showed that the induced VTG
      content in all of the experimental groups stabilized after 10 days, except for
      the 10,000ng/L experimental group, in which the induced VTG content decreased
      after 10 days. A 17beta-estradiol-VTG10day response curve was then established
      based on the induced VTG content in the 0, 10, 100 and 1000ng/L experimental
      groups at day 10. After establishing the curve, male M. nipponense were captured
      from the upper, middle and lower reaches of the Chuo-shui River, the Beigang
      River, the Jishui River, the Agongdian River and the Sichong River in Taiwan, and
      the VTG content in these prawns was determined. In addition, the p-EEQ in the
      waters was determined based on the VTG content, and the estradiol equivalent
      concentration (EEQ) in the waters was also measured immediately after sampling
      using the solid-phase extraction-enzyme-linked immunosorbent assay (SPE-ELISA)
      method. The results showed that the p-EEQ in the middle and lower reaches of the
      rivers in certain parts of Taiwan ranged from 38 to 400ng/L, and the detection
      rate was 100%. Moreover, the EEQ ranged from 7.9 to 92.9ng/L, and the detection
      rate was 42.9%, indicating that most of the middle and lower reaches of the
      rivers in Taiwan were polluted by xeno-estrogens. The 17beta-estradiol
      concentrations determined based on the p-EEQ were all higher than those based on
      the EEQ (SPE-ELISA method). The results of the present study showed that the use
      of M. nipponense to determine the p-EEQ in environmental waters provided
      advantages that included a high detection rate, high sensitivity and convenience.
      However, the p-EEQ cannot be used in waters that do not contain M. nipponense.

PMID- 27886524
TI  - Effects of ethanol on cocaine self-administration in monkeys responding under a
      second-order schedule of reinforcement.
AB  - BACKGROUND: Concurrent alcohol use among cocaine abusers is common but the
      behavioral variables that promote co-abuse are not well understood. The present
      study examined the effects of intragastric (i.g.) ethanol (EtOH) administration
      in monkeys responding under a schedule of cocaine reinforcement in which
      extensive drug seeking was maintained by conditioned stimuli. METHODS: Four adult
      male cynomolgus monkeys (Macaca fascicularis) were trained to respond under a
      second-order fixed-interval (FI) 600s (fixed-ratio (FR) 30:S) schedule of cocaine
      (0.003-0.56mg/kg/injection) presentation. Sessions ended after 5 injections or
      90min had elapsed. Different EtOH doses (0.5-2.0g/kg, i.g.) were administered
      30min before the session, typically on Tuesdays and Fridays. Blood ethanol
      concentrations (BECs) were also assessed. Pattern of FI responding was assessed
      by determining quarter-life (QL) values. RESULTS: Cocaine self-administration was
      characterized as an inverted U-shaped function of dose; QL values increased
      monotonically with dose. EtOH pretreatments dose-dependently decreased self
      administration at several cocaine doses in 3 of 4 monkeys. In one animal, EtOH
      increased low-dose cocaine-maintained responding. For all monkeys, QL values were
      increased by EtOH when low- and high-cocaine doses were self-administered,
      suggesting additive effects of EtOH and cocaine. Furthermore, BECs were not
      altered following cocaine self-administration. CONCLUSIONS: The reductions in
      cocaine self-administration and the increases in QL values following EtOH,
      suggest that EtOH was enhancing cocaine-related conditioned reinforcement. A
      better understanding of the behavioral mechanisms that mediate the co-abuse of
      alcohol and cocaine will lead to improved treatments for both drugs.

PMID- 27886526
TI  - Food and beverage product reformulation as a corporate political strategy.
AB  - Product reformulation- the process of altering a food or beverage product's
      recipe or composition to improve the product's health profile - is a prominent
      response to the obesity and noncommunicable disease epidemics in the U.S. To
      date, reformulation in the U.S. has been largely voluntary and initiated by
      actors within the food and beverage industry. Similar voluntary efforts by the
      tobacco and alcohol industry have been considered to be a mechanism of corporate
      political strategy to shape public health policies and decisions to suit
      commercial needs. We propose a taxonomy of food and beverage industry corporate
      political strategies that builds on the existing literature. We then analyzed the
      industry's responses to a 2014 U.S. government consultation on product
      reformulation, run as part of the process to define the 2015 Dietary Guidelines
      for Americans. We qualitatively coded the industry's responses for predominant
      narratives and framings around reformulation using a purposely-designed coding
      framework, and compared the results to the taxonomy. The food and beverage
      industry in the United States used a highly similar narrative around voluntary
      product reformulation in their consultation responses: that reformulation is
      "part of the solution" to obesity and NCDs, even though their products or
      industry are not large contributors to the problem, and that progress has been
      made despite reformulation posing significant technical challenges. This
      narrative and the frames used in the submissions illustrate the four categories
      of the taxonomy: participation in the policy process, influencing the framing of
      the nutrition policy debate, creating partnerships, and influencing the
      interpretation of evidence. These strategic uses of reformulation align with
      previous research on food and beverage corporate political strategy.

PMID- 27886527
TI  - Universal health coverage at the macro level: Synthetic control evidence from
      Thailand.
AB  - As more and more countries are moving towards Universal Health Coverage (UHC), it
      is important to understand the macro level or aggregate impacts of such a policy.
      We use synthetic control methods to study the impact of UHC, introduced in
      Thailand in 2001, on various macroeconomic and health outcomes. Thailand is
      compared to a weighted average of control countries in terms of aggregate health
      financing indicators, aggregate health outcomes and economic performance, over
      the period 1995 to 2012. Our results suggest that UHC helps alleviate the
      financial consequences of illnesses. The estimated treatment effect of UHC on out
      of-pocket payments as a percentage of overall health expenditures is negative 13
      percentage points and its effect on annual government per capita health spending
      is US$ 79. We detect a smaller effect of US$ 60.8 on total health spending per
      capita which appears with a lag. We document positive health effects as captured
      by reductions in infant and child mortality. We do not find any effect on GDP and
      the share of the government budget devoted to health. Overall, our results
      complement micro evidence based on within country variation. The counterfactual
      design implemented here may be used to inform other countries on the macro level
      repercussions of UHC.

PMID- 27886529
TI  - Autobiographical and episodic memory deficits in mild traumatic brain injury.
AB  - Those who have suffered a concussion, otherwise known as a mild traumatic brain
      injury (mTBI), often complain of lingering memory problems. However, there is
      little evidence in the behavioral literature reliably demonstrating memory
      deficits. Thus, in the present study, cognitive profiles including measures of
      general executive functioning and processing speed, as well as episodic and
      semantic memory were collected in younger and older adult participants with or
      without a remote (>1year prior to testing) mTBI. We first investigated whether
      there were observable episodic and autobiographical memory impairments associated
      with mTBI within an otherwise healthy young group. Next, because previous work
      had demonstrated some overlap in patterns of behavioral impairment in normally
      aging adults and younger adults with a history of mTBI (e.g. Ozen, Fernandes,
      Clark, & Roy, 2015), we sought to determine whether these groups displayed
      similar cognitive profiles. Lastly, we conducted an exploratory analysis to test
      whether having suffered an mTBI might exacerbate age-related cognitive decline.
      Results showed the expected age-related decline in episodic memory performance,
      coupled with a relative preservation of semantic memory in older adults.
      Importantly, this pattern was also present in younger adults with a history of
      remote mTBI. No differences were observed across older adult groups based on mTBI
      status. Logistic regression analyses, using each measure in our battery as a
      predictor, successfully classified mTBI status in younger participants with a
      high degree of specificity (79.5%). These results indicate that those who have
      had an mTBI demonstrate a distinct cognitive signature, characterized by
      impairment in episodic and autobiographical memory, coupled with a relative
      preservation of semantic memory.

PMID- 27886528
TI  - Neighborhood social stressors, fine particulate matter air pollution, and
      cognitive function among older U.S. adults.
AB  - A growing number of studies have found a link between outdoor air pollution and
      cognitive function among older adults. Psychosocial stress is considered an
      important factor determining differential susceptibility to environmental hazards
      and older adults living in stressful neighborhoods may be particularly vulnerable
      to the adverse health effects of exposure to hazards such as air pollution. The
      objective of this study is to determine if neighborhood social stress amplifies
      the association between fine particulate matter air pollution (PM2.5) and poor
      cognitive function in older, community-dwelling adults. We use data on 779 U.S.
      adults ages 55 and older from the 2001/2002 wave of the Americans' Changing Lives
      study. We determined annual average PM2.5 concentration in 2001 in the area of
      residence by linking respondents with EPA air monitoring data using census tract
      identifiers. Cognitive function was measured using the number of errors on the
      Short Portable Mental Status Questionnaire (SPMSQ). Exposure to neighborhood
      social stressors was measured using perceptions of disorder and decay and
      included subjective evaluations of neighborhood upkeep and the presence of
      deteriorating/abandoned buildings, trash, and empty lots. We used negative
      binomial regression to examine the interaction of neighborhood perceived stress
      and PM2.5 on the count of errors on the cognitive function assessment. We found
      that the association between PM2.5 and cognitive errors was stronger among older
      adults living in high stress neighborhoods. These findings support recent
      theoretical developments in environmental health and health disparities research
      emphasizing the synergistic effects of neighborhood social stressors and
      environmental hazards on residents' health. Those living in socioeconomically
      disadvantaged neighborhoods, where social stressors and environmental hazards are
      more common, may be particularly susceptible to adverse health effects of social
      and physical environmental exposures.

PMID- 27886530
TI  - Choosing wisely: The impact of patient selection on efficacy and safety outcomes
      in the EINSTEIN-DVT/PE and AMPLIFY trials.
AB  - BACKGROUND: The results of the EINSTEIN-DVT/PE and AMPLIFY trials, which compared
      rivaroxaban and apixaban with conventional anticoagulation therapy for acute
      venous thromboembolism (VTE), respectively, are often compared. However, the
      trials differed in duration of therapy (3-12 and 6months, respectively) and in
      patient selection (few exclusion criteria and more stringent exclusion criteria,
      respectively). METHODS: To determine the effect of these methodological
      differences on outcomes, the patients enrolled in EINSTEIN-DVT/PE were divided
      into 2 cohorts; the 5253 patients that matched the exclusion criteria for AMPLIFY
      and were treated for at least 6months (cohort 1) and the 2368 patients who would
      have been ineligible for AMPLIFY (cohort 2). RESULTS: Compared with patients in
      cohort 2, those in cohort 1 were older and more often male and there were more
      with unprovoked VTE, prior VTE, cancer and known thrombophilia. In cohort 1,
      rivaroxaban would have significantly reduced recurrent VTE (relative risk [RR],
      0.64; 95% confidence interval [CI], 0.43-0.95) and major bleeding (RR, 0.50; 95%
      CI, 0.30-0.82) compared with conventional therapy, whereas the two treatments
      would have had similar effects on recurrent VTE (RR, 1.08; 95% CI, 0.65-1.79) and
      major bleeding (RR, 1.03; 95% CI, 0.48-2.18) in cohort 2. CONCLUSIONS: This
      analysis illustrates the influence of patient selection and treatments duration
      on outcome results and highlights the limitations of cross-trial comparisons.

PMID- 27886531
TI  - Coagulation and sepsis.
AB  - Severe sepsis is almost invariably associated with systemic activation of
      coagulation. There is ample evidence that demonstrates a wide-ranging cross-talk
      between hemostasis and inflammation, which is probably implicated in the
      pathogenesis of organ dysfunction in patients with sepsis. Inflammation not only
      leads to initiation and propagation of coagulation activity, but coagulation also
      markedly influences inflammation. Molecular mechanisms that play a role in
      inflammation-induced effects on coagulation have been recognized in much detail.
      Pro-inflammatory cells and cyto- and chemokines can activate the coagulation
      system and downregulate crucial physiological anticoagulant mechanisms.
      Initiation of coagulation activation and consequent thrombin generation is caused
      by expression of tissue factor on activated monocytes and endothelial cells and
      is ineffectually offset by tissue factor pathway inhibitor. At the same time,
      endothelial-associated anticoagulant pathways, in particular the protein C
      system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is
      severely obstructed by inactivation of the endogenous fibrinolytic system, mainly
      as a result of upregulation of its principal inhibitor, plasminogen activator
      inhibitor type 1 (PAI-1). Increased fibrin generation and impaired break down
      lead to deposition of (micro)vascular clots, which may contribute to tissue
      ischemia and ensuing organ dysfunction. The foundation of the management of
      coagulation in sepsis is the explicit and thorough treatment of the underlying
      disorder by antibiotic treatment and source control measures. Adjunctive
      strategies focused at the impairment of coagulation, including anticoagulants and
      restoration of physiological anticoagulant mechanisms, may supposedly be
      indicated and have been found advantageous in experimental and initial clinical
      trials.

PMID- 27886532
TI  - Enantioselective metabolism and enantiomerization of benalaxyl in mice.
AB  - The enantiomerization and enantioselective metabolism of benalaxyl in mice after
      a single gavage administration were investigated in the present study. The
      pharmacokinetic result indicated that elimination of (-)-R-benalaxyl in plasma
      was slightly faster with the t1/2 of 26.65 h and 28.88 h for (-)-R- and (+)-S
      benalaxyl, respectively. Consistent with this, elimination in tissues and
      excretion were also enantioselective, with (+)-S-benalaxyl enriched in all
      tissues, urine and feces. And formation of the metabolites also exhibited an
      enantioselective manner. Both benalaxyl and most of its metabolites exhibited a
      potent excretion to feces and urine. In addition, significant enantiomerization
      of benalaxyl enantiomers was observed in plasma, with a larger extent from R to S
      than S to R. Thus, this difference in enantiomerization may be one of the reasons
      to explain the enantioselective enrichment of (+)-S-benalaxyl in mice observed in
      this study. Data from this study proves that besides metabolic enzymes,
      enantiomerization could be another important factor that contributes to the
      enantioselective metabolism of a chiral pesticide. Thus, research at enantiomeric
      level is necessary for efficient risk assessment of chiral pesticides.

PMID- 27886533
TI  - Toxicological effects of dimethomorph on soil enzymatic activity and soil
      earthworm (Eisenia fetida).
AB  - The objective of this study was to evaluate the toxicity of the fungicide
      dimethomorph to soil microbial activity and the earthworm Eisenia fetida.
      Multiple biomarkers, namely, four soil enzymes (urease, dehydrogenase, invertase,
      and acid phosphatase), four earthworm biochemical indices (dismutase, catalase,
      cellulase, and malondialdehyde), and the transcriptional levels of both target
      genes (dismutase and catalase) were measured at 1, 10, and 100 mg kg-1 after 1,
      7, 21, and 28 days. The degradation rate of dimethomorph in soil was also
      determined, and the results indicated that most parameters did not differ from
      the controls at 1 and 10 mg kg-1 dimethomorph by the last exposure time (28 d).
      However, high concentrations (100 mg kg-1) of dimethomorph had varying effects on
      soil enzymatic activity and earthworms. These effects gradually decreased with
      prolonged exposure times. Positive correlations (R2 > 0.57) between the target
      gene expression levels and antioxidant enzyme activities were observed in this
      study. We also found that earthworms have improved soil microbial activity and
      accelerated the degradation of dimethomorph. Overall, higher concentrations of
      dimethomorph might pose an ecological hazard to soil environments in the short
      term.

PMID- 27886534
TI  - Differences in the response of soil dehydrogenase activity to Cd contamination
      are determined by the different substrates used for its determination.
AB  - Dehydrogenase activity (DHA) is an important indicator of heavy metal toxicity in
      contaminated soils. Different instances of DHA were determined using various
      substrates and which could affect the description of heavy metal toxicity.
      Currently, too few investigations have been done on selecting appropriate
      substrates. This study employed indoor simulation to determine soil DHA and its
      response to external cadmium (Cd) using two substrates (TTC and INT). Hormesis
      for DHA obtained using the TTC method (DHA-TTC) in low Cd concentration was
      observed which was quickly inhibited in high Cd concentration. While DHA obtained
      using the INT method (DHA-INT) decreased slowly when Cd concentration increased.
      The DHA-TTC and DHA-INT in soils at Cd concentration of 500 mg kg-1 decreased 86%
      and 53%, respectively, compared to the control. The dose-response relationship of
      Cd to DHA can be well simulated using the logistic model (p < 0.01), which
      indicated DHA could be used to indicate soil Cd toxicity. Multiple stepwise
      regression analysis revealed that total organic matter (TOC) is the major factor
      influencing the toxicity of Cd to DHA-TTC, while TOC, pH and cation exchange
      capacity (CEC) are major factors influencing the toxicity of Cd to DHA-INT. The
      different responses of soil DHA-TTC and DHA-INT to Cd are due to the differences
      in electron transport chain characteristics between TTC and INT, as well as the
      influence of soil properties. Although both DHA-TTC and DHA-INT can monitor soil
      Cd contamination, DHA-INT is recommended as a superior bio-indicator to indicate
      and assess contamination of Cd in soil.

PMID- 27886535
TI  - Risk assessment for the mercury polluted site near a pesticide plant in Changsha,
      Hunan, China.
AB  - The distribution characteristics of mercury fractions at the site near a
      pesticide plant was investigated, with the total mercury concentrations ranging
      from 0.0250 to 44.3 mg kg-1. The mercury bound to organic matter and residual
      mercury were the main fractions, and the most mobile fractions accounted for only
      5.9%-9.7%, indicating a relatively low degree of potential risk. The
      relationships between mercury fractions and soil physicochemical properties were
      analysed. The results demonstrated that organic matter was one of the most
      important factors in soil fraction distribution, and both OM and soil pH appeared
      to have a significant influence on the Fe/Mn oxides of mercury. Together with the
      methodology of partial correlation analysis, the concept and model of delayed
      geochemical hazard (DGH) was introduced to reveal the potential transformation
      paths and chain reactions among different mercury fractions and therefore to have
      a better understanding of risk development. The results showed that the site may
      be classified as a low-risk site of mercury DGH with a probability of 10.5%, but
      it had an easy trend in mercury DGH development due to low critical points of DGH
      burst. In summary, this study provides a methodology for site risk assessment in
      terms of static risk and risk development.

PMID- 27886536
TI  - Rare earths and trace elements contents in leaves: A new indicator of the
      composition of atmospheric dust.
AB  - The relationship between the trace element distribution in atmospheric particles
      and leaves of some exposed plants in the environment was recently demonstrated.
      This indication would suggest that the trace element analysis of leaves in these
      plants could provide information about the composition, nature and origin of the
      atmospheric dust dispersed in the environment. In order to corroborate this
      hypothesis, the distribution of trace elements and Rare Earths were studied in
      leaves of some endemic plants, in the atmospheric fallout and in soils of rural,
      urban and industrial ecosystems in Sicily. These elements have been chosen to
      discriminate the source and nature of different source on atmospheric dust and
      the larger capability of the composition of the latter materials to influence the
      metal ion distribution in leaves of studied plants rather than the soil
      composition. These evidences are related to the recognition both of positive La
      anomaly and trace element enrichments in studied leaves and to their particular
      V/Th and Co/Ni signature. On the other hand, some particular normalised REE
      features recognised in leaves suggest that a limited contribution to the REE
      budget in studied leaves is provided by the REE migration from roots.

PMID- 27886538
TI  - Study of the presence of PCDDs/PCDFs on zero-valent iron nanoparticles.
AB  - Studies show that nanoscale zero-valent iron (nZVI) particles enhance the
      formation of chlorinated compounds such as polychlorinated dioxins and furans
      (PCDD/Fs) during thermal processes. However, it is unclear whether nZVI acts as a
      catalyst for the formation of these compounds or contains impurities, such as
      PCDD/Fs, within its structure. We analyzed the presence of PCDD/Fs in nZVI
      particles synthesized through various production methods to elucidate this
      uncertainty. None of the 2,3,7,8-substituted congeners were found in the
      commercially-produced nZVI, but they were present in the laboratory-synthesized
      nZVI produced through the borohydride method, particularly in particles
      synthesized from iron (III) chloride rather than from iron sulfate. Total PCDD/F
      WHO-TEQ concentrations of up to 35 pg/g were observed in nZVI particles, with
      hepta- and octa-chlorinated congeners being the most abundant. The reagents used
      in the borohydride method were also analyzed, and our findings suggest that FeCl3
      effectively contains PCDD/Fs at concentrations that could explain the
      concentrations observed in the nZVI product. Both FeCl3 and nZVI showed a similar
      PCDD/F patterns with slight differences. These results suggest that PCDD/Fs might
      transfer from FeCl3 to nZVI during the production method, and thus, care should
      be taken when employing certain nZVI for environmental remediation.

PMID- 27886537
TI  - Bioelectrochemical approach for reductive and oxidative dechlorination of
      chlorinated aliphatic hydrocarbons (CAHs).
AB  - A sequential reductive-oxidative treatment was developed in this study in a
      continuous-flow bioelectrochemical reactor to address bioremediation of
      groundwater contaminated by trichloroethene (TCE) and less-chlorinated but still
      harmful intermediates, such as vinyl chloride. In order to optimize the anodic
      compartment, whereby the oxygen-driven microbial oxidation of TCE-daughter
      products occurs, abiotic batch experiments were performed with various anode
      materials poised at +1.20 V vs. SHE (i.e., graphite rods and titanium mesh anode
      coated with mixed metal oxides (MMO)) and setups (i.e., electrodes embedded
      within a bed of silica beads or graphite granule). The MMO anode displayed higher
      efficiency (>90%) for oxygen generation compared to the graphite electrodes.
      Additionally, the graphite bed presence adversely affects oxygen generation,
      likely due to the oxygen scavenging. This effect was completely eliminated by
      replacing the graphite granules with silica beads. The anodic setups were
      thereafter verified in a mentioned reactor at an applied TCE loading rate of
      approximately 20 MUM d-1 and a hydraulic retention time of 1.4 d in each
      compartment. The cathode consisted of a bed of graphite granules and was
      potentiostatically controlled at -0.65 V vs. SHE. The best reactor performance in
      terms of removal efficiency (i.e., >97%), removal rate (i.e., 121.8 +/- 2.7 MUeq
      L-1 d-1), and the residual concentration (i.e., 5.03 +/- 0.63 MUeq L-1) of
      chlorinated contaminants was achieved with the MMO anode placed in a silica bed.
      Ecotoxicity tests performed with algae confirmed these results by showing
      progressive toxicity reduction from inlet to cathodic and anodic effluent using
      this reactor configuration.

PMID- 27886539
TI  - Understanding reduced inorganic mercury accumulation in rice following selenium
      application: Selenium application routes, speciation and doses.
AB  - Selenium (Se) has recently been demonstrated to reduce inorganic mercury (IHg)
      accumulation in rice plants, while its mechanism is far from clear. Here, we
      aimed at exploring the potential effects of Se application routes (soil or foliar
      application with Se), speciation (selenite and selenate), and doses on IHg-Se
      antagonistic interactions in soil-rice systems. Results of our pot experiments
      indicated that soil application but not foliar application could evidently reduce
      tissue IHg concentrations (root: 0-48%, straw: 15-58%, and brown rice: 26-74%),
      although both application routes resulted in comparable Se accumulation in
      aboveground tissues. Meanwhile, IHg distribution in root generally increased with
      amended Se doses in soil, suggesting antagonistic interactions between IHg and Se
      in root. These results provided initial evidence that IHg-Se interactions in the
      rhizosphere (i.e., soil or rice root), instead of those in the aboveground
      tissues, could probably be more responsible for the reduced IHg bioaccumulation
      following Se application. Furthermore, Se dose rather than Se speciation was
      found to be more important in controlling IHg accumulation in rice. Our findings
      regarding the importance of IHg-Se interactions in the rhizosphere, together with
      the systematic investigation of key factors affecting IHg-Se antagonism and IHg
      bioaccumulation, advance our understanding of Hg dynamics in soil-rice systems.

PMID- 27886540
TI  - The effect of different pyrolysis temperatures on the speciation and availability
      in soil of P in biochar produced from the solid fraction of manure.
AB  - Biochar application to agricultural land has been proposed as a means for
      improving phosphorus (P) availability in soil. The purpose of the current study
      was to understand how pyrolysis temperature affects P speciation in biochar and
      how this affects availability of P in the amended soil. Biochar was produced at
      different temperatures from digestate solids. The primary species of P in
      digestate solids were simple calcium phosphates. However, a high co-occurrence of
      magnesium (Mg) and P, indicated that struvite or other magnesium phosphates may
      also be important species. At low temperatures, pyrolysis had little effect on P
      speciation; however, as the temperature increased above 600  degrees C, the P
      gradually became more thermodynamically stable in species such as apatite. At
      very high temperatures above 1000  degrees C, there were indications of reduced
      forms of P. Biochar production decreased the immediate availability of P in
      comparison with the original digestate solids. However, for biochar produced at
      low temperatures, availability quickly increased to the same levels as in the
      digestate solids. For biochar produced at higher temperatures, availability
      remained depressed for much longer. The low availability of P in the biochar
      produced at high temperatures can probably be explained by the formation of less
      soluble P species in the biochar. In contrast, the transient decrease of
      availability of the P in the biochar produced at low temperatures can be
      explained by mechanisms, such as sorption on biochar, which gradually decreases
      because of oxidation of the biochar surfaces or changes in pH around the biochar
      particles.

PMID- 27886541
TI  - Long-term effects of nickel oxide nanoparticles on performance, microbial
      enzymatic activity, and microbial community of a sequencing batch reactor.
AB  - The nitrogen and phosphorus removal, microbial enzymatic activity, and microbial
      community of a sequencing batch reactor (SBR) were evaluated under long-term
      exposure to nickel oxide nanoparticles (NiO NPs). High NiO NP concentration (over
      5 mg L-1) affected the removal of chemical oxygen demand, nitrogen, and
      phosphorus. The presence of NiO NP inhibited the microbial enzymatic activities
      and reduced the nitrogen and phosphorus removal rates of activated sludge. The
      microbial enzymatic activities of the activated sludge showed a similar variation
      trend to the nitrogen and phosphorus removal rates with the increase in NiO NP
      concentration from 0 to 60 mg L-1. The Ni content in the effluent and activated
      sludge showed an increasing trend with the increase in NiO NP concentration. Some
      NiO NPs were absorbed on the sludge surface or penetrate the cell membrane into
      the interior of microbial cells in the activated sludge. NiO NP facilitated the
      increase in reactive oxygen species by disturbing the balance between the
      oxidation and anti-oxidation processes, and the variation in lactate
      dehydrogenase demonstrated that NiO NP could destroy the cytomembrane and cause
      variations in the microbial morphology and physiological function. High
      throughput sequencing demonstrated that the microbial community of SBR had some
      obvious changes at 0-60 mg L-1 NiO NPs at the phyla, class and genus levels.

PMID- 27886542
TI  - Occurrence of perfluoroalkyl substances in cord serum and association with growth
      indicators in newborns from Beijing.
AB  - Perfluoroalkyl substances (PFASs), a group of environmental pollutants,
      persistently exist in the environment. To investigate the associations between
      PFASs levels in cord serum and birth weight, birth length and ponderal index, we
      measured PFASs in cord serum samples from 170 infants from Feb. 2012 to Jun. 2012
      in Beijing, China. The mean concentrations in cord serum samples for
      perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS),
      perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA),
      perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnA) were 1.285
      ng/mL, 1.228 ng/mL, 0.230 ng/mL, 0.224 ng/mL, 0.100 ng/mL and 0.085 ng/mL,
      respectively. First-born children had slightly higher exposure levels of PFHxS (p
      < 0.001) and PFOA (p = 0.03) than second-born or third-born children. The
      spearman correlation coefficients with gestation time were individually 0.160 (p
      = 0.038) for PFHxS and 0.202 (p = 0.008) for PFOA. Both univariate and
      multivariate linear regression analysis showed that the exposure levels of PFASs
      had no statistically significant associations with birth weight, birth length or
      ponderal index in the present population. For male infants, we observed that
      PFHxS positively correlated with birth length, but the levels of PFUnA were
      negatively associated with birth length.

PMID- 27886543
TI  - Interactions among triphenyltin degradation, phospholipid synthesis and membrane
      characteristics of Bacillus thuringiensis in the presence of d-malic acid.
AB  - Degradation pathway and surface biosorption of triphenyltin (TPT) by effective
      microbes have been investigated in the past. However, unclear interactions among
      membrane components and TPT binding and transport are still obstacles to
      understanding TPT biotransformation. To reveal the mechanism involved, the
      phospholipid expression, membrane potential, cellular mechanism and molecular
      dynamics between TPT and fatty acids (FAs) during the TPT degradation process in
      the presence of d-malic acid (DMA) were studied. The results show that the
      degradation efficiency of 1 mg L-1 TPT by Bacillus thuringiensis (1 g L-1) with
      0.5 or 1 mg L-1 DMA reached values up to approximately 90% due to the promotion
      of element metabolism and cellular activity, and the depression of FA synthesis
      induced by DMA. The addition of DMA caused conversion of more linoleic acid into
      10-oxo-12(Z)-octadecenoic acid, increased the membrane permeability, and
      alleviated the decrease in membrane potential, resulting in TPT transport and
      degradation. Fluorescence analysis reveals that the endospore of B. thuringiensis
      could act as an indicator for membrane potential and cellular activities. The
      current findings are advantageous for acceleration of biosorption, transport and
      removal of pollutants from natural environments.

PMID- 27886544
TI  - 3-Aroylindoles display antitumor activity in vitro and in vivo: Effects of N1
      substituents on biological activity.
AB  - A series of 3-aroylindole hydroxamic acids (10-17) were developed based on the
      concept of a structural combination of tubulin and histone deacetylase (HDAC)
      inhibitors. This was accomplished by introducing hydroxamic acid-containing
      moieties at the N1 position of the tubulin assembly inhibitor, compound 9
      (SCB01A, BPR0L075, phase II trial). Most of synthetic compounds produced in this
      way displayed comparable HDAC inhibitory activity, and four (10, 12-14) of them
      also inhibit tubulin assembly. Notably, compound 12 possesses not only tubulin
      and HDAC inhibitory activity but also shows HDAC6 selectivity over other HDAC
      isoforms. In addition, it exhibits remarkable inhibitory activity against the
      growth cancer cells in vitro and in vivo (PC3 and RPMI-8226 cells). Notably, it
      suppresses the growth of multiple myeloma xenografts without leading to the death
      of teated animals like reference compound. In sum, this study provided potential
      compounds with safer profiles for cancer treatment.

PMID- 27886545
TI  - Design, synthesis, docking studies and biological evaluation of novel dihydro
      1,3,5-triazines as human DHFR inhibitors.
AB  - A novel series of dihydro-1,3,5-triazine derivatives bearing a heteroatom spiro
      ring were designed and synthesized on the basis of molecular flexible docking
      work, and their biological activities were evaluated. Compounds A2, A5, B1 and B3
      showed potent human dihydrofolate reductase (hDHFR) inhibitory activity with IC50
      values of 7.46 nM, 3.72 nM, 6.46 nM, 4.08 nM, versus reference drug methotrexate
      (MTX). From the molecular docking result we concluded that the conformation space
      generated by deformation of the flexible residue Phe31 is favorable for the
      binding of the spiro-ring, and inserting heteroatom into spiro ring might
      increase the binding affinity. There were 24 compounds with broadspectrum
      antiproliferative activity against several tumor cell lines (HCT116, A549, HL-60,
      HepG2 and MDA-MB-231) with IC50 values ranging from 0.79 to 0.001 MUM. The
      antitumor activity in vivo of compound A2 was determined in a human alveolar
      basal epithelial cell line A549 xenograft model. This study offered novel
      anticancer agents with high inhibitory activity that target hDHFR and have a
      binding mode of the novel molecular scaffold with hDHFR. This provides potent
      support for further development of novel hDHFR inhibitors.

PMID- 27886547
TI  - Comprehensive review on various strategies for antimalarial drug discovery.
AB  - The resistance of malaria parasites to existing drugs carries on growing and
      progressively limiting our ability to manage this severe disease and finally lead
      to a massive global health burden. Till now, malaria control has relied upon the
      traditional quinoline, antifolate and artemisinin compounds. Very few new
      antimalarials were developed in the past 50 years. Among recent approaches,
      identification of novel chemotherapeutic targets, exploration of natural products
      with medicinal significance, covalent bitherapy having a dual mode of action into
      a single hybrid molecule and malaria vaccine development are explored heavily.
      The proper execution of these approaches and proper investment from international
      agencies will accelerate the discovery of drugs that provide new hope for the
      control or eventual eradication of this global infectious disease. This review
      explores various strategies for assessment and development of new antimalarial
      drugs. Current status and scientific value of previous approaches are
      systematically reviewed and new approaches provide a pragmatic forecast for
      future developments are introduced as well.

PMID- 27886546
TI  - Biology-oriented drug synthesis (BIODS): In vitro beta-glucuronidase inhibitory
      and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl
      carboxylate derivatives.
AB  - Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2
      methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1-26, by
      treating metronidazole with different aryl and hetero-aryl carboxylic acids in
      the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures
      of all synthetic derivatives were confirmed with the help of various
      spectroscopic techniques such as EI-MS, 1H -NMR and 13C NMR. CHN elemental
      analyses were also found in agreement with the calculated values. Synthetic
      derivatives were evaluated to check their beta-glucuronidase inhibitory activity
      which revealed that except few derivatives, all demonstrated good inhibition in
      the range of IC50 = 1.20 +/- 0.01-60.30 +/- 1.40 MUM as compared to the standard
      d-saccharic acid 1,4-lactone (IC50 = 48.38 +/- 1.05 MUM). Compounds 1, 3, 4, 6, 9
      19, and 21-24 were found to be potent analogs and showed superior activity than
      standard. Limited structure-activity relationship is suggested that the molecules
      having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better
      activity than the compounds with electron donating groups such as Me, OMe and
      BuO. To verify these interpretations, in silico study was also performed, a good
      correlation was observed between bioactivities and docking studies.

PMID- 27886549
TI  - Enhanced adsorbability and photocatalytic activity of TiO2-graphene composite for
      polycyclic aromatic hydrocarbons removal in aqueous phase.
AB  - Photodegradation via titanium dioxide (TiO2) has been used to remove polycyclic
      aromatic hydrocarbons (PAHs) from environmental media broadly. In this study, a
      series of TiO2-graphene composites (P25-GR) with different GR weight ratios were
      synthesized via hydrothermal reaction of graphene oxide (GO) and P25. Their
      structures were characterized and the proprieties were tested in aqueous phase.
      Phenanthrene (PHE), fluoranthene (FLAN), and benzo[a]pyrene (BaP) were selected
      as models of PAHs. The experiment indicated that P25-2.5%GR exhibited enhancement
      in both adsorption and photodegradation, ~80% of PAHs were removed after 2h
      photocatalysis. The influence of photodegradation rate was studied, including
      PAHs initial concentration and pH. Aromatic intermediates were identified during
      the reaction process and the degradation pathways were portrayed. This work
      explored the enhanced photocatalysis performance was attributed to the PAH
      selective adsorbability and the strong electron transfer ability of the
      composite. The analysis of the degradation intermediates confirmed that the
      reaction proceeded with the formation of free radicals, leading to the gradual
      PAH mineralization.

PMID- 27886548
TI  - Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anti
      cancer agents for lung cancer.
AB  - The nuclear factor-kappa B (NF-kappaB) signaling pathway has been targeted for
      the therapy of various cancers, including lung cancer. EF24 was considered as a
      potent inhibitor of NF-kappaB signaling pathway. In this study, a series of
      asymmetric EF24 analogues were synthesized and evaluated for their anti-cancer
      activity against three lung cancer cell lines (A549, LLC, H1650). Most of the
      compounds exhibited good anti-tumor activity. Among them, compound 81 showed
      greater cytotoxicity than EF24. Compound 81 also possessed a potent anti
      migration and anti-proliferative ability against A549 cells in a concentration
      dependent manner. Moreover, compound 81 induced lung cancer cells death by
      inhibiting NF-kappaB signaling pathway, and activated the JNK-mitochondrial
      apoptotic pathway by increasing reactive oxygen species (ROS) generation
      resulting in apoptosis. In summary, compound 81 is a valuable candidate for anti
      lung cancer therapy.

PMID- 27886550
TI  - Vgamma1+gammadeltaT, early cardiac infiltrated innate population dominantly
      producing IL-4, protect mice against CVB3 myocarditis by modulating IFNgamma+ T
      response.
AB  - Viral myocarditis (VMC) is an inflammation of the myocardium closely associated
      with Coxsackievirus B3 (CVB3) infection. Vgamma1+gammadeltaT cells, one of early
      cardiac infiltrated innate population, were reported to protect CVB3 myocarditis
      while the precise mechanism not fully addressed. To explore cytokine profiles and
      kinetics of Vgamma1+gammadeltaT and mechanism of protection against VMC, flow
      cytometry was conducted on cardiac Vgamma1 cells in C57BL/6 mice following CVB3
      infection. The level of cardiac inflammation, transthoracic echocardiography and
      viral replication were evaluated after monoclonal antibody depletion of
      Vgamma1gammadeltaT. We found that Vgamma1+gammadeltaT cells infiltration peaked
      in the heart at day3 post CVB3 infection and constituted a minor source of IFN
      gamma but major producers for early IL-4. Vgamma1gammadeltaT cells were activated
      earlier holding a higher IL-4-producing efficiency than CD4+Th cells in the
      heart. Depletion of Vgamma1+gammadeltaT resulted in a significantly exacerbated
      cardiac infiltration, increased T, macrophage and neutrophil population in heart
      homogenates and worse cardiomyopathy; which was accompanied by a significant
      expansion of peripheral IFNgamma+CD4+ and CD8+T cells. Neutralization of IL-4 in
      mice resulted in an exacerbated acute myocarditis confirming the IL-4-mediated
      protective mechanism of Vgamma1. Our findings identify a unique property of
      Vgamma1+gammadeltaT cells as one dominant early producers of IL-4 upon CVB3 acute
      infection which is a key mediator to protect mice against acute myocarditis by
      modulating IFNgamma-secreting T response.

PMID- 27886551
TI  - Reconsidering azobenzene as a component of small-molecule hypoxia-mediated cancer
      drugs: A theranostic case study.
AB  - An azobenzene scaffold serves as both a fluorescence quencher and nitrogen
      mustard deactivator in a mitochondrial targeting unit bearing theranostic drug
      delivery system (DDS). The DDS exhibited a tissue selectivity for tumors with
      aggressive phenotypes, and the efficient in vitro and in vivo azoreduction under
      hypoxia conditions resulted in bright fluorescence at the tumor site as well as
      the in situ activation of the prodrug. In vivo therapeutic experiments
      demonstrated a significant reduction in tumor growth versus number of controls
      and ex vivo tissue analysis confirmed tissue normalization with strongly reduced
      angiogenic markers and suppressed cell proliferation. Mechanistic insight of the
      DDS's mode of action was gained by gene and protein expression experiments, aided
      by a proteomic analysis, revealing the circumvention of cellular drug resistance
      pathways as well as the normalization of Slit-Robo signaling, and the involvement
      of granzyme-triggered mitochondria-mediated apoptosis. Overall, the combined high
      sensitivity and synthetic ease as well as excellent therapeutic response suggests
      a revival of the azobenzene class of hypoxia activated drugs, especially applied
      to theranostics, is warranted.

PMID- 27886553
TI  - Mechanical stress regulates transport in a compliant 3D model of the blood-brain
      barrier.
AB  - Transport of fluid and solutes is tightly controlled within the brain, where
      vasculature exhibits a blood-brain barrier and there is no organized lymphatic
      network facilitating waste transport from the interstitial space. Here, using a
      compliant, three-dimensional co-culture model of the blood-brain barrier, we show
      that mechanical stimuli exerted by blood flow mediate both the permeability of
      the endothelial barrier and waste transport along the basement membrane.
      Application of both shear stress and cyclic strain facilitates tight junction
      formation in the endothelial monolayer, with and without the presence of
      astrocyte endfeet in the surrounding matrix. We use both dextran perfusion and
      TEER measurements to assess the initiation and maintenance of the endothelial
      barrier, and microparticle image velocimetry to characterize the fluid dynamics
      within the in vitro vessels. Application of pulsatile flow to the in vitro
      vessels induces pulsatile strain to the vascular wall, providing an opportunity
      to investigate stretch-induced transport along the basement membrane. We find
      that a pulsatile wave speed of approximately 1 mm/s with Womersley number of
      0.004 facilitates retrograde transport of high molecular weight dextran along the
      basement membrane between the basal endothelium and surrounding astrocytes.
      Together, these findings indicate that the mechanical stress exerted by blood
      flow is an important regulator of transport both across and along the walls of
      cerebral microvasculature.

PMID- 27886552
TI  - Three dimensional electrospun PCL/PLA blend nanofibrous scaffolds with
      significantly improved stem cells osteogenic differentiation and cranial bone
      formation.
AB  - Nanofibrous scaffolds that are morphologically/structurally similar to natural
      ECM are highly interested for tissue engineering; however, the electrospinning
      technique has the difficulty in directly producing clinically relevant 3D
      nanofibrous scaffolds with desired structural properties. To address this
      challenge, we have developed an innovative technique of thermally induced
      nanofiber self-agglomeration (TISA) recently. The aim of this work was to prepare
      (via the TISA technique) and evaluate 3D electrospun PCL/PLA blend (mass ratio:
      4/1) nanofibrous scaffolds having high porosity of ~95.8% as well as
      interconnected and hierarchically structured pores with sizes from sub
      micrometers to ~300 MUm for bone tissue engineering. The hypothesis was that the
      incorporation of PLA (with higher mechanical stiffness/modulus and bioactivity)
      into PCL nanofibers would significantly improve human mesenchymal stem cells
      (hMSCs) osteogenic differentiation in vitro and bone formation in vivo. Compared
      to neat PCL-3D scaffolds, PCL/PLA-3D blend scaffolds had higher mechanical
      properties and in vitro bioactivity; as a result, they not only enhanced the cell
      viability of hMSCs but also promoted the osteogenic differentiation. Furthermore,
      our in vivo studies revealed that PCL/PLA-3D scaffolds considerably facilitated
      new bone formation in a critical-sized cranial bone defect mouse model. In
      summary, both in vitro and in vivo results indicated that novel 3D electrospun
      PCL/PLA blend nanofibrous scaffolds would be strongly favorable/desired for hMSCs
      osteogenic differentiation and cranial bone formation.

PMID- 27886554
TI  - A biomaterial-assisted mesenchymal stromal cell therapy alleviates colonic
      radiation-induced damage.
AB  - Healthy tissues surrounding abdomino-pelvic tumours can be impaired by
      radiotherapy, leading to chronic gastrointestinal complications with substantial
      mortality. Adipose-derived Mesenchymal Stromal Cells (Ad-MSCs) represent a
      promising strategy to reduce intestinal lesions. However, systemic administration
      of Ad-MSCs results in low cell engraftment within the injured tissue.
      Biomaterials, able to encapsulate and withstand Ad-MSCs, can overcome these
      limitations. A silanized hydroxypropylmethyl cellulose (Si-HPMC) hydrogel has
      been designed and characterized for injectable cell delivery using the operative
      catheter of a colonoscope. We demonstrated that hydrogel loaded-Ad-MSCs were
      viable, able to secrete trophic factors and responsive to the inflammatory
      environment. In a rat model of radiation-induced severe colonic damage, Ad-MSC +
      Si-HPMC improve colonic epithelial structure and hyperpermeability compared with
      Ad-MSCs injected intravenously or locally. This therapeutic benefit is associated
      with greater engraftment of Si-HPMC-embedded Ad-MSCs in the irradiated colonic
      mucosa. Moreover, macrophage infiltration near the injection site was less
      pronounced when Ad-MSCs were embedded in the hydrogel. Si-HPMC induces modulation
      of chemoattractant secretion by Ad-MSCs that could contribute to the decrease in
      macrophage infiltrate. Si-HPMC is suitable for cell delivery by colonoscopy and
      induces protection of Ad-MSCs in the tissue potentiating their therapeutic effect
      and could be proposed to patients suffering from colon diseases.

PMID- 27886555
TI  - Overcoming multidrug resistance via simultaneous delivery of cytostatic drug and
      P-glycoprotein inhibitor to cancer cells by HPMA copolymer conjugate.
AB  - Multidrug resistance (MDR) is a common cause of failure in chemotherapy for
      malignant diseases. MDR is either acquired as a result of previous repeated
      exposure to cytostatic drugs (P388/MDR cells) or naturally, as some tumors are
      congenitally resistant to chemotherapy (CT26 cells). One of the most common
      mechanisms of MDR is upregulation of P-glycoprotein (P-gp) expression. Here, we
      used HPMA copolymer conjugates, whereby the cytostatic drug doxorubicin (Dox) or
      the derivative of the P-gp inhibitor reversin 121 (R121) or both were covalently
      bound through a degradable pH-sensitive hydrazone bond. We proved that R121, when
      bound to a polymeric carrier, is capable of inhibiting P-gp in P388/MDR cells and
      sensitizing them in relation to the cytostatic activity of Dox. Conjugate bearing
      both Dox and R121 was found to be far more potent in P388/MDR cells than
      conjugate bearing Dox alone or a mixture of conjugates bearing either Dox or R121
      when cytostatic activity in vitro, cell cycle arrest, accumulation of Dox in
      cells and induction of apoptosis were determined. Importantly, conjugate bearing
      R121 is also effective in vivo as it inhibits P-gp in P388/MDR tumors after
      intraperitoneal administration, while both the conjugate bearing Dox and R121
      induces apoptosis in P388/MDR tumors more effectively than conjugate bearing Dox
      alone. Only conjugate bearing Dox and R121 significantly inhibited P388/MDR tumor
      growth and led to the prolonged survival of treated mice. However, the most
      dramatic antitumor activity of this conjugate was found in the CT26 tumor model
      where it completely cured six out of eight experimental mice, while conjugate
      bearing Dox alone cured no mice.

PMID- 27886556
TI  - Modular delivery of CpG-incorporated lipid-DNA nanoparticles for spleen DC
      activation.
AB  - We introduce a versatile carrier system for in vitro and in vivo immune
      stimulation based on soft matter DNA nanoparticles (NPs). The incorporation of
      lipid-modified nucleotides into DNA strands enables the formation of micelles of
      uniform size. In a single self-assembly step, the micelles can be equipped with
      immune adjuvant (CpG) motifs and fluorescent probes. The immunological effects of
      CpG confined at the NP surface were studied in a comprehensive manner in animal
      experiments. Dose-dependent activation of spleen dendritic cells (DCs) by CpG
      conjugated NP was observed, which was accompanied by the pronounced up-regulation
      of co-stimulatory molecule and cytokine production.

PMID- 27886557
TI  - Upconversion optical/magnetic resonance imaging-guided small tumor detection and
      in vivo tri-modal bioimaging based on high-performance luminescent nanorods.
AB  - In this work, we demonstrated multifunctional NaYbF4: Tm3+/Gd3+ upconversion (UC)
      nanorods (UCNRs) with near-infrared (NIR)-to-NIR emission and controlled phase
      and size for UC optical and T1/T2 dual-weighted magnetic resonance (MR) imaging
      guided small tumor detection and tri-modal bioimaging. Cell toxicity and post
      injection histology results revealed that our designed UCNRs present low
      biotoxicity and good biocompatibility in living animals. Real-time tracking based
      on UCNRs in living mice demonstrated that the UCNRs were mainly accumulated in
      the reticuloendothelial system (RES) and excreted through the hepatic pathway.
      Additionally, the UCNRs exhibited high X-ray absorption coefficient and large K
      edge value, resulting in efficient in vivo CT imaging. A new type of binary
      (Yb3+/Gd3+) MR contrast agent for simultaneous T1/T2 dual-weighted MR imaging was
      achieved by doping Gd3+ into NaYbF4 host. Importantly, a small tumor (5 mm in
      diameter) could be detected in vivo by intravenously injecting UCNRs under UC
      optical and MR imaging modalities. Therefore, these multifunctional nanoprobes
      based on NaYbF4:Tm3+/Gd3+ UCNRs with remarkable NIR-to-NIR emission provide
      potential applications for tri-modal UC optical, CT, binary T1/T2 MR imaging, and
      early-stage tumor detection in nanomedicine.

PMID- 27886558
TI  - Optimization of sparse phase encodings for variable repetition-delay turbo-spin
      echo (TSE) T1 measurements for preclinical applications.
AB  - A variable repetition-delay (TR) spin echo sequence with repeated refocusing
      pulses, i.e., a variable TR turbo-spin echo (TSE), provides an attractive means
      of acquiring an accurate T1 map information that is free from gradient echo based
      artifacts such as magnetic field inhomogeneities particularly for ultra-high
      field (at 7T and above) preclinical applications. However, the applicability of
      multi-slice TSE sequences is often limited by signal distortion from T2
      relaxation due to echo-train acquisitions for short T2 tissues, inter-slice cross
      talks and magnetization transfer (MT) from repetitive slice-selective 180 degrees
      pulse, and extended scan times with multiple TR excitations. These TSE
      shortcomings are difficult to remedy for preclinical applications, where small
      sizes of target organs usually limit the slice-gap control with restricted
      parallel imaging capabilities. In this study, compressed-sensing-assisted turbo
      spin echo (CS-TSE) acquisitions for variable TR T1 measurements at 7T preclinical
      scanner were implemented to reduce the echo-trains by sparse phase encodings.
      Following the sparse signal simulation and sampling scheme optimization, the
      measured T1 values from CS-TSE and TSE were compared for phantoms, ex vivo, and
      in vivo subjects. The phantom T1 values from CS-TSE and TSE were identical to
      those from the inversion recovery spin echo. For both ex vivo and in vivo multi
      slice T1 mapping, the shortened echo-trains of CS-TSE relieved the T2 relaxation,
      reduced the inter-slice interferences of multi-slice acquisition, and made room
      for additional slice encodings while maintaining a shorter scan time than the
      conventional TSE at the expense of local image smoothness from CS
      regularizations.

PMID- 27886560
TI  - Serum metalloproteinase 9 levels increase after generalized tonic-clonic
      seizures.
AB  - Metalloproteinase 9 (MMP9) is a member of a family of enzymes that mediate the
      degradation of extracellular matrix proteins, and is especially involved in blood
      brain barrier maintenance. Increased levels of MMP9 have been observed in many
      neurological disorders, including epilepsy, suggesting it may be involved in the
      pathogenesis of seizures. We investigated changes in MMP9 serum levels after
      acute seizures in epilepsy patients. Concentrations of MMP9 in serum were
      measured by ELISA in 43 patients 1-3, 24, and 72h after generalized tonic-clonic
      seizure and once in participants of the control group. MMP9 levels were
      significantly increased 1-3 and 24h after seizure and decreased to control levels
      72h after seizure. Our results suggest that MMP9 is released after or just before
      seizure; however, further studies are needed to resolve the consequences of the
      observed MMP9 increase.

PMID- 27886559
TI  - Ectopic expression of GA 2-oxidase 6 from rapeseed (Brassica napus L.) causes
      dwarfism, late flowering and enhanced chlorophyll accumulation in Arabidopsis
      thaliana.
AB  - Gibberellins (GAs) are endogenous hormones that play an important role in higher
      plant growth and development. GA2-oxidase (GA2ox) promotes catabolism and
      inactivation of bioactive GAs or their precursors. In this study, we identified
      the GA2-oxidase gene, BnGA2ox6, and found it to be highly expressed in the
      silique and flower. Overexpression of BnGA2ox6 in Arabidopsis resulted in GA
      deficiency symptoms, including inhibited elongation of the hypocotyl and stem,
      delayed seed germination, and late flowering. BnGA2ox6 overexpression reduced
      silique growth, but had no effect on seed development. Additionally, BnGA2ox6
      overexpression enhanced chlorophyll b and total chlorophyll accumulation, and
      downregulated mRNA expression levels of the CHL1 and RCCR genes, which are
      involved in the chlorophyll degradation. These findings suggest that BnGA2ox6
      regulates plant hight, silique development, flowering and chlorophyll
      accumulation in transgenic Arabidopsis.

PMID- 27886561
TI  - The STOP-BANG questionnaire improves the detection of epilepsy patients at risk
      for obstructive sleep apnea.
AB  - Patients with epilepsy and obstructive sleep apnea (OSA) are at risk for worsened
      seizure control and quality of life. We performed a quality improvement project,
      evaluating for improvements in the screening of OSA in epilepsy patients using
      the STOP-BANG questionnaire. The electronic medical records of patients seen in
      our epilepsy clinic were screened for 4 months prior to the intervention. We
      subsequently implemented the STOP-BANG questionnaire for 3 months. Only 22/664
      patients (3.3%) had their sleeping habits explored during the pre-intervention
      period; 11 (1.7%) were referred to sleep medicine. Following implementation of
      the STOP-BANG questionnaire, the percentage of patients screened for OSA
      increased to 41.6% (269/647, Chi-square Fisher's Exact test 2-sided p<0.001). Of
      the 269 patients screened, 84 (31.2%) met criteria for elevated OSA risk. Forty
      one patients were referred to sleep medicine during the subsequent 3 month
      period, including 33 who met STOP-BANG criteria for OSA. This represented 6.3%
      and 5.1% (respectively) of all 647 patients, a significant improvement over the
      percentage referred prior to the intervention (Chi-square Fisher's Exact test 2
      sided p<0.001). Twelve of the 33 patients referred based on the STOP-BANG
      questionnaire saw sleep medicine; 11 (91.7%) were referred for polysomnography
      (PSG). Of the 10 patients who underwent PSG, 9 (90%) were diagnosed with OSA and
      offered treatment with continuous positive airway pressure (CPAP).

PMID- 27886562
TI  - Magnetic susceptibility, artifact volume in MRI, and tensile properties of swaged
      Zr-Ag composites for biomedical applications.
AB  - Zr-Ag composites were fabricated to decrease the magnetic susceptibility by
      compensating for the magnetic susceptibility of their components. The Zr-Ag
      composites with a different Zr-Ag ratio were swaged, and their magnetic
      susceptibility, artifact volume, and mechanical properties were evaluated by
      magnetic balance, three-dimensional (3-D) artifact rendering, and a tensile test,
      respectively. These properties were correlated with the volume fraction of Ag
      using the linear rule of mixture. We successfully obtained the swaged Zr-Ag
      composites up to the reduction ratio of 96% for Zr-4, 16, 36, 64Ag and 86% for Zr
      81Ag. However, the volume fraction of Ag after swaging tended to be lower than
      that before swaging, especially for Ag-rich Zr-Ag composites. The magnetic
      susceptibility of the composites linearly decreased with the increasing volume
      fraction of Ag. No artifact could be estimated with the Ag volume fraction in the
      range from 93.7% to 95.4% in three conditions. Young's modulus, ultimate tensile
      strength (UTS), and 0.2% yield strength of Zr-Ag composites showed slightly lower
      values compared to the estimated values using a linear rule of mixture. The
      decrease in magnetic susceptibility of Zr and Ag by alloying or combining would
      contribute to the decrease of the Ag fraction, leading to the improvement of
      mechanical properties.

PMID- 27886563
TI  - Nanomechanical properties, wear resistance and in-vitro characterization of Ta2O5
      nanotubes coating on biomedical grade Ti-6Al-4V.
AB  - Tantalum pentoxide nanotubes (Ta2O5 NTs) can dramatically raise the biological
      functions of different kinds of cells, thus have promising applications in
      biomedical fields. In this study, Ta2O5 NTs were prepared on biomedical grade Ti
      6Al-4V alloy (Ti64) via physical vapor deposition (PVD) and a successive two-step
      anodization in H2SO4: HF (99:1)+5% EG electrolyte at a constant potential of 15V.
      To improve the adhesion of nanotubular array coating on Ti64, heat treatment was
      carried out at 450 degrees C for 1h under atmospheric pressure with a
      heating/cooling rate of 1 degrees Cmin-1. The surface topography and composition
      of the nanostructured coatings were examined by atomic force microscopy (AFM) and
      X-ray electron spectroscopy (XPS), to gather information about the corrosion
      behavior, wear resistance and bioactivity in simulated body fluids (SBF). From
      the nanoindentation experiments, the Young's modulus and hardness of the 5min
      anodized sample were ~ 135 and 6GPa, but increased to ~ 160 and 7.5GPa,
      respectively, after annealing at 450 degrees C. It was shown that the corrosion
      resistance of Ti64 plates with nanotubular surface modification was higher than
      that of the bare substrate, where the 450 degrees C annealed specimen revealed
      the highest corrosion protection efficiency (99%). Results from the SBF tests
      showed that a bone-like apatite layer was formed on nanotubular array coating, as
      early as the first day of immersion in simulated body fluid (SBF), indicating the
      importance of nanotubular configuration on the in-vitro bioactivity.

PMID- 27886565
TI  - Investigating the relationship between reduced self-awareness of falls risk,
      rehabilitation engagement and falls in older adults.
AB  - The present study aimed to investigate whether self-awareness of falls risk is
      associated with rehabilitation engagement, motivation for rehabilitation, and
      number of falls after hospital discharge. The sample comprised 91 older adults
      (Mage=77.97, SD=8.04) undergoing inpatient rehabilitation. The Self-Awareness of
      Falls Risk Measure (SAFRM) was used to measure different aspects of self
      awareness. The treating physiotherapist and occupational therapist rated the
      patient's engagement in rehabilitation and the patient reported his/her
      motivation for treatment. Falls information was collected from the patient and
      significant other once a month for three months following hospital discharge.
      Significant correlations were found between physiotherapist-rated engagement and
      intellectual (rs=-0.22, p<0.05) and anticipatory awareness (rs=-0.24, p<0.05).
      Occupational therapist-rated engagement and patient-reported motivation for
      rehabilitation was correlated with emergent awareness (rs=-0.38 and -0.31,
      p<0.05, respectively) and overall self-awareness (rs=-0.31 and -0.26, p<0.05,
      respectively). Regression analyses indicated that overall self-awareness provided
      a unique contribution to occupational therapist-rated engagement when controlling
      for age, gender, cognition and functional ability. Falls were reported by 29.9%
      of participants, however, self-awareness did not differ significantly between
      fallers and non-fallers. The findings suggest that self-awareness of falls risk
      is associated with rehabilitation engagement and motivation. Therefore, improving
      patient self-awareness of falls risk may increase engagement in therapy leading
      to better patient outcomes.

PMID- 27886564
TI  - C-reactive protein is related to future cognitive impairment and decline in
      elderly individuals with cardiovascular disease.
AB  - AIMS: To explore the association of C-reactive protein (CRP) plasma levels with
      subsequent cognitive performance and decline among elderly individuals with pre
      existing cardiovascular disease (CVD), and to assess the role of cerebrovascular
      indices in this relationship. METHODS: CRP levels were measured in a subgroup of
      individuals with chronic CVD, who previously participated in a secondary
      prevention trial. Cognitive performance was evaluated 14.7+/-1.9 and 19.9+/
      1.0years after entry to the trial. A validated set of computerized cognitive
      tests was used (Neurotrax Computerized Cognitive Battery) to assess performance
      globally and in memory, executive function, visuospatial and attention domains.
      Linear regression and mixed models were used to assess the relationship of CRP
      plasma levels with cognitive scores and decline, respectively. In addition, we
      tested whether cerebrovascular reactivity, carotid intima media thickness and
      presence of carotid plaques modify these associations. RESULTS: Among 536
      participants (mean age at the first cognitive evaluation 72.6+/-6.4years; 95%
      males), CRP at the top tertile vs. the rest was associated with subsequent poorer
      performance overall (beta=-2.2+/-1.0; p=0.031) and on tests of executive function
      and attention (beta=-2.3+/-1.1; p=0.043 and beta=-2.0+/-1.4; p=0.047,
      respectively). Moreover, CRP levels were positively related to a greater decline
      in executive functions (beta=-2.4+/-1.1; p=0.03). These associations were
      independent of potential confounders and were not modified by cerebrovascular
      indices. CONCLUSION: Our findings suggest that systemic chronic inflammation,
      potentially associated with underlying atherosclerosis, is related to cognitive
      impairment and decline two decades later, in elderly individuals with pre
      existing CVD.

PMID- 27886566
TI  - Disentangling development of sensation seeking, risky peer affiliation, and binge
      drinking in adolescent sport.

PMID- 27886567
TI  - Evaluation of 8-hydroxy-2-deoxyguanosine and NFkB activation, oxidative stress
      response, acetylcholinesterase activity, and histopathological changes in rainbow
      trout brain exposed to linuron.
AB  - Linuron is a widely used herbicide to control grasses and annual broad leaf
      weeds. It is known that linuron has toxic effects on different organisms.
      However, the toxic effects of linuron on aquatic organisms, especially fish, is
      completely unknown. Thus, we aimed to investigate changes in 8-hydroxy-2
      deoxyguanosine (8-OHdG) and nuclear factor kappa B (NFkB) activity,
      histopathological changes, antioxidant responses and acetylcholinesterase (AChE)
      activity in rainbow trout brain after exposure to linuron. Fish were exposed to
      30MUg/L, 120MUg/L and 240MUg/L concentrations of linuron for twenty-one days.
      Brain tissues were taken from fish for 8-OHdG and NFkB activity,
      histopathological examination and determination of superoxide dismutase (SOD),
      catalase (CAT) enzyme activity, lipid peroxidation (LPO), and reduced glutathione
      (GSH) levels. Our data indicated that high linuron concentrations caused a
      decrease in GSH levels, SOD and CAT activities in brain tissues (p<0.05). LPO
      levels were significantly increased by 240MUg/L linuron. All concentrations
      caused a significant inhibition in brain AChE enzyme activity (p<0.05).
      Immunopositivity was detected for 8-OHdG and NFkB, and linuron exposure caused
      histopathological damage to the brain tissues. The results of this study can
      provide useful information for understanding of linuron-induced toxicity.

PMID- 27886568
TI  - Deep sequencing methods for protein engineering and design.
AB  - The advent of next-generation sequencing (NGS) has revolutionized protein
      science, and the development of complementary methods enabling NGS-driven protein
      engineering have followed. In general, these experiments address the functional
      consequences of thousands of protein variants in a massively parallel manner
      using genotype-phenotype linked high-throughput functional screens followed by
      DNA counting via deep sequencing. We highlight the use of information rich
      datasets to engineer protein molecular recognition. Examples include the creation
      of multiple dual-affinity Fabs targeting structurally dissimilar epitopes and
      engineering of a broad germline-targeted anti-HIV-1 immunogen. Additionally, we
      highlight the generation of enzyme fitness landscapes for conducting fundamental
      studies of protein behavior and evolution. We conclude with discussion of
      technological advances.

PMID- 27886570
TI  - Menarche, menstrual problems and suicidal behavior in Chinese adolescents.
AB  - BACKGROUND: Menarche is the first menstrual cycle. Menstrual problems, such as
      dysmenorrheal menorrhagia, oligomenorrhea, and irregular cycle are common in
      female adolescents. This research aims to examine the associations between age at
      menarche and menstrual problems and suicidal behavior among Chinese female
      adolescents. METHODS: An epidemiological survey of 5831 female adolescents from
      eight high schools of three counties of Shandong province, China, was conducted.
      A self-administered paper-and-pencil questionnaire was used to collect
      information. Logistic regression analyses were used to examine the association
      between menstruation and suicidality. RESULTS: The mean age of the sample was
      15.02 (SD=1.44) years. Of the sample, 5,231 (90.0%) had experienced their first
      menstrual cycle, and 23.2%, 10.4%, and 4.5% of the sample reported having had
      suicidal ideation, plan and attempt, respectively. In multivariate models,
      menarche at <=11 years was associated with increased risk of suicidal ideation
      (OR=1.41, 95%CI: 1.10-1.81) and menarche at 12 years was associated with suicide
      plan (OR=1.23, 95%CI: 1.00-1.51). Irregular menstrual cycle was significantly
      associated with increased risk of suicidal ideation (OR=1.40, 95%CI: 1.05-1.86)
      and menstrual period less than or equal to 4 days was significantly associated
      with increased risk of suicide plan (OR=1.32, 95%CI: 1.06-1.66). LIMITATIONS:
      This cross-sectional study cannot establish the causal directions between
      menstrual problems and suicidality in adolescents. CONCLUSIONS: Our study
      suggests that earlier menarche, irregular menstrual cycle and short menstrual
      period are associated with suicidal behavior in female adolescents. Further
      research is warranted to examine the causal relationship between menstrual
      problems and suicidal behavior in adolescents.

PMID- 27886569
TI  - Effects of a right unilateral ultrabrief pulse electroconvulsive therapy course
      on health related quality of life in elderly depressed patients.
AB  - INTRODUCTION: Patients with Major Depressive Disorder (MDD) referred for
      electroconvulsive therapy (ECT) have poorer Health Related Quality of Life
      (HRQOL), compared with other patients with MDD, but ECT is associated with
      significant and durable improvement in HRQOL. However, no prior research has
      focused exclusively on elderly patients with MDD receiving ECT. METHODS: HRQOL
      data from 240 depressed patients over the age of 60 was measured with the Medical
      Outcomes Study Short Form 36 (SF-36). The SF-36 was measured before and after a
      course of acute ECT. Predictors of change in HRQOL scores were identified by
      generalized linear modeling. RESULTS: At baseline, participants showed very poor
      HRQOL. After treatment with ECT, the full sample showed marked and significant
      improvement across all SF-36 measures, with the largest gains seen in dimensions
      of mental health. Across all participants, the Physical Component Summary (PCS)
      score improved by 2.1 standardized points (95% CI, 0.61,3.56), while the Mental
      Component Summary (MCS) score improved by 12.5 points (95% CI, 7.2,10.8) Compared
      with non-remitters, remitters showed a trend toward greater improvement in the
      PCS summary score of 2.7 points (95%CI, -0.45, 5.9), while the improvement in the
      MCS summary score was significantly greater (8.5 points, 95% CI, 4.6,12.3) in the
      remitters than non-remitters. Post-ECT SF-36 measurements were consistently and
      positively related to baseline scores and remitter/non-remitter status or change
      in depression severity from baseline. Objective measures of cognitive function
      had no significant relationships to changes in SF-36 scores. LIMITATIONS: This
      study's limitations include that it was an open label study with no comparison
      group, and generalizability is limited to elderly patients. DISCUSSION: ECT
      providers and elderly patients with MDD treated with ECT can be confident that
      ECT will result in improved HRQOL in the short-term. Attaining remission is a key
      factor in the improvement of HRQOL. Acute changes in select cognitive functions
      were outweighed by improvement in depressive symptoms in determining the short
      term HRQOL of the participants treated with ECT.

PMID- 27886571
TI  - Apigenin inhibited hypoxia induced stem cell marker expression in a head and neck
      squamous cell carcinoma cell line.
AB  - OBJECTIVE: Cancer stem cells contribute to tumor recurrence, and a hypoxic
      environment is critical for maintaining cancer stem cells. Apigenin is a natural
      product with anticancer activity. However, the effect of apigenin on cancer stem
      cells remains unclear. Our aim was to investigate the effect of apigenin on
      cancer stem cell marker expression in head and neck squamous cell carcinoma cells
      under hypoxia. DESIGN: We used three head and neck squamous cell carcinoma cell
      lines; HN-8, HN-30, and HSC-3. The mRNA expression of cancer stem cell markers
      was determined by semiquantitative RT-PCR and Real-time PCR. The cytotoxic effect
      of apigenin was determined by MTT colorimetric assay. Flow cytometry was used to
      reveal the number of cells expressing cancer stem cell surface markers. RESULTS:
      HN-30 cells, a cancer cell line from the pharynx, showed the greatest response to
      hypoxia by increasing their expression of CD44, CD105, NANOG, OCT-4, REX-1, and
      VEGF. Apigenin significantly decreased HN-30 cell viability in dose- and time
      dependent manners. In addition, 40MUM apigenin significantly down-regulated the
      mRNA expression of CD44, NANOG, and CD105. Consistent with these results, the
      hypoxia-induced increase in CD44+ cells, CD105+ cells, and STRO-1+ cells was
      significantly abolished by apigenin. CONCLUSION: Apigenin suppresses cancer stem
      cell marker expression and the number of cells expressing cell surface markers
      under hypoxia.

PMID- 27886574
TI  - The differential relationship between mental contamination and the core
      dimensions of contact contamination fear.
AB  - Two types of contamination fear are recognized: contact and mental contamination.
      Contact contamination appears to be motivated both by harm avoidance and disgust
      avoidance. This study aimed to examine the relationships between disgust
      propensity, mental contamination and contact contamination while differentiating
      between harm avoidance and disgust avoidance in contact contamination. 169 OCD
      patients completed a set of questionnaires assessing mental contamination,
      contact contamination, disgust propensity, OCD, anxiety and depression. 1)
      Contact contamination based on disgust avoidance was more strongly associated
      with mental contamination and disgust propensity than contact contamination based
      on harm avoidance; 2) mental contamination significantly predicted contact
      contamination based on disgust avoidance, while it did not predict contact
      contamination based on harm avoidance; 3) mental contamination had a significant
      mediational role in the relationship between disgust propensity and contact
      contamination motivated by disgust avoidance. Mental contamination plays a role
      in contact contamination fear when disgust is primarily experienced.

PMID- 27886573
TI  - Nuclear transportation of exogenous epidermal growth factor receptor and androgen
      receptor via extracellular vesicles.
AB  - Epidermal growth factor receptor (EGFR) plays a central role in the progression
      of several human malignancies. Although EGFR is a membrane receptor, it undergoes
      nuclear translocation, where it has a distinct signalling pathway. Herein, we
      report a novel mechanism by which cancer cells can directly transport EGFR to the
      nucleus of other cells via extracellular vesicles (EVs). The transported receptor
      is active and stimulates the nuclear EGFR pathways. Interestingly, the
      translocation of EGFR via EVs occurs independently of the nuclear localisation
      sequence that is required for nuclear translocation of endogenous EGFR. Also, we
      found that the mutant receptor EGFRvIII could be transported to the nucleus of
      other cells via EVs. To assess the role of EVs in the regulation of an actual
      nuclear receptor, we studied the regulation of androgen receptor (AR). We found
      that full-length AR and mutant variant ARv7 are secreted in EVs derived from
      prostate cancer cell lines and could be transported to the nucleus of AR-null
      cells. The EV-derived AR was able to bind the androgen-responsive promoter region
      of prostate specific antigen, and recruit RNA Pol II, an indication of active
      transcription. The nuclear-translocated AR via EVs enhanced the proliferation of
      acceptor cells in the absence of androgen. Finally, we provide evidence that
      nuclear localisation of AR could occur in vivo via orthotopically-injected EVs in
      male SCID mice prostate glands. To our knowledge, this is the first study showing
      the nuclear translocation of nuclear receptors via EVs, which significantly
      extends the role of EVs as paracrine transcriptional regulators.

PMID- 27886572
TI  - A rapid and sensitive UHPLC-MS/MS method for quantification of 83b1 in plasma and
      its application to bioavailability study in rats.
AB  - Great attentions have been drawn by quinoline for its broad bioactivity as anti
      fungal, anti-bacterial and anti-tumor activities. Compared with cisplatin, 83b1,
      a quinoline derivative, showed equal activity in anti-tumor and lower
      cyctotoxicity in normal cell. In this study, a simple, rapid and sensitive method
      for determination of 83b1 in rat plasma using UHPLC-MS/MS was developed for the
      first time. Loratadine was used as an internal standard (IS). Separation was
      performed on an Xterra MS C18 column by isocratic elution using acetonitrile:
      water solution with 10/00 formic acid (90:10, v/v) as mobile phase at a flow rate
      of 0.3mL/min. A triple quadrupole mass spectrometer operating in the positive ion
      switching electron spray ionization mode with selection reaction monitoring (SRM)
      was employed to determine 83b1 and IS transitions of m/z 321.82->147.84, 382.71
      >258.76 for 83b1 and Loratadine, respectively. The values of specificity,
      linearity and lower limit of quantification, intra- and inter- day precision and
      accuracy, extraction recovery, matrix effect and stability for this method
      satisfied the acceptable limits. The lower limit of quantification was 0.5ng/mL
      with a linear range of 0.5-1500ng/mL. The validated method was employed to study
      the bioavailability of 83b1 in rat by dosing with intravenous injection (1mg/kg)
      and gavage (10mg/kg), and the oral bioavailability of 83b1 in rat was calculated
      as 20.9+/-8.8%.

PMID- 27886575
TI  - An evaluation of the appropriateness and effectiveness of structured reflection
      for midwifery students in Ireland.
AB  - Midwifery students undertaking the undergraduate midwifery education programme in
      Ireland participate in facilitated reflective sessions that aim to develop their
      skills of reflecting on and in clinical practice. This paper presents a
      qualitative evaluation of the appropriateness and effectiveness of the
      facilitated reflection sessions for pre and post-registration midwifery students
      in two large Dublin maternity teaching hospitals. The aim was to evaluate
      structured reflective practice sessions which sought to assist midwifery students
      to become competent reflective practitioners. Group reflection sessions were
      conducted weekly in a clinical practice area at the same time each week over one
      academic year. After the series of structured reflective sessions, midwifery
      students and facilitating staff were invited to evaluate the reflective process.
      This evaluation consisted of a self-completion survey to identify the factors
      that facilitated and impeded student participation in the sessions. Respondents
      answered a series of questions about the reflective practice sessions and were
      also invited to enter qualitative data regarding their subjective experiences of
      the process in free text boxes. The data were then collated into themes by an
      independent reviewer. The results of the evaluation clearly indicate that
      midwifery students and facilitators welcomed the opportunity to engage in group
      reflection sessions as a form of peer support and as a catalyst for learning from
      clinical practice. Findings suggest that reflective practice can contribute to
      the development of skilled, self-aware and engaged practitioners.

PMID- 27886576
TI  - The effect of early goal-directed therapy for treatment of severe sepsis or
      septic shock: A systemic review and meta-analysis.
AB  - PURPOSE: To assess the effects of early goal-directed therapy (EGDT) on reducing
      mortality compared with conventional management of severe sepsis or septic shock.
      MATERIALS AND METHODS: We included a systemic review, using the Medline and
      EMBASE. Seventeen randomized trials with 5765 patients comparing EGDT with usual
      care were included. RESULTS: There were no significant differences in mortality
      between EGDT and control groups (relative risk [RR], 0.89; 95% confidence
      interval [CI], 0.79-1.00), with moderate heterogeneity (I2=56%). The EGDT was
      associated with lower mortality rates when the mortality rate of the usual care
      group was greater than 30% (12 trials; RR, 0.83; 95% CI, 0.72-0.96), but not when
      the mortality rate in the usual care group was less than 30% (5 trials; RR, 1.03;
      95% CI, 0.92-1.16). The mortality benefit was seen only in subgroup of population
      analyzed between publication of the 2004 and 2012 Surviving Sepsis Campaign
      guidelines, but not before and after these publications. CONCLUSION: This meta
      analysis was heavily influenced by the recent addition of the trio of trials
      published after 2014. The results of the recent trio of trials may be biased due
      to methodological issues. This includes lack of blinding by incorporating similar
      diagnostic and therapeutic interventions as the original EGDT trial.

PMID- 27886577
TI  - High-flow nasal cannula oxygen therapy vs conventional oxygen therapy in cardiac
      surgical patients: A meta-analysis.
AB  - INTRODUCTION: The use of high-flow nasal cannula (HFNC) for the treatment of many
      diseases has gained increasing popularity. In the present meta-analysis, we aimed
      to assess the efficacy and safety of HFNCs compared with conventional oxygen
      therapy (COT) in adult postextubation cardiac surgical patients. METHOD: We
      reviewed the Embase, PubMed, Cochrane Central Register of Controlled Trials,
      Wanfang databases, and the China National Knowledge Infrastructure. Two
      investigators independently collected the data and assessed the quality of each
      study. RevMan 5.3 was used for the present meta-analysis. RESULTS: We included
      495 adult postextubation cardiac surgical patients. There was no significant
      heterogeneity among the studies. Compared with COT, HFNCs were associated with a
      significant reduction in the escalation of respiratory support (risk ratio, 0.61;
      95% confidence interval [CI], 0.46-0.82; z = 3.32, P < .001). There were no
      significant differences in the reintubation rate (risk ratio, 0.96; 95% CI, 0.04
      24.84; z = 0.02, P = .98) or length of intensive care unit stay (weighted mean
      difference, 0.13; 95% CI, -0.88 to 7.92; z = 1.57, P = .12) between the 2 groups.
      No severe complications were reported in either group. CONCLUSIONS: The HFNC
      could reduce the need for escalation of respiratory support compared with COT,
      and it could be safely administered in adult postextubation cardiac surgical
      patients.

PMID- 27886578
TI  - Kynurenic acid and psychotic symptoms and personality traits in twins with
      psychiatric morbidity.
AB  - Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF)
      have been reported in patients with schizophrenia and bipolar disorder. The aim
      of the present study was to investigate cytokines and kynurenines in the CSF of
      twin pairs discordant for schizophrenia or bipolar disorder and to study these
      CSF markers in relation to psychotic symptoms and personality traits. CSF levels
      of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and
      tumor necrosis factor-alpha (TNF-alpha) were analyzed in 23 twins with
      schizophrenia or bipolar disorder, and in their not affected co-twins. Ratings of
      psychotic symptoms and personality traits were made using the Scales for
      Assessment of Negative and Positive symptoms, the Structured Clinical Interview
      for DSM-IV - Axis II Disorders, and the Schizotypal Personality Questionnaire -
      Brief. A total score for psychotic symptoms and personality traits was
      constructed for analysis. CSF KYNA was associated with the score for psychotic
      symptom and personality traits. TNF-alpha and IL-8 were associated, and the intra
      pair differences scores of TNF-alpha and IL-8 were highly correlated. Intraclass
      correlations indicated genetic influences on CSF KYNA, TRP, IL-8 and TNF-alpha.
      The association between KYNA and psychotic symptoms further supports a role of
      KYNA in psychotic disorders.

PMID- 27886579
TI  - A cytokine study of pediatric Tourette's disorder without obsessive compulsive
      disorder.
AB  - It has been suggested that post-infectious inflammation in central nervous system
      is a cause of tic disorder including Tourette's disorder (TD). Since pro
      inflammatory cytokines are important mediators inducing inflammation, the
      cytokine levels are regarded as one of the important indicators of inflammation.
      Several studies have investigated the relationship of autoimmunity and the
      pathogenesis of TD by measuring the inflammatory cytokine levels of blood.
      However, when using human samples, the experimental results can be affected by
      the factors like size of sample, comorbidity, medication that patients take and
      the severity of the diseases. Thus, it is important to exclude the possibility
      that comorbidity and medication affects the level of inflammatory cytokines in
      the serum of TD patients. In our experiment, we recruited 29 patients without
      obsessive compulsive disorder (OCD) comorbidity and the majority of these
      patients did not take medication. The six pro-inflammatory cytokine levels of
      blood between patient and healthy groups were compared, considering the factors
      above, to determine more accurate results. Of the cytokines we investigated, the
      interleukin 12 p70 (IL-12p70) and tumor necrosis factor alpha (TNFalpha) levels
      increased in patient group compared to healthy controls and the patient group
      which have anti-streptolysin O (ASO) score under the 200 or YTGSS score from 10
      to 19 also showed higher IL-12p70 or TNFalpha levels. In addition, the patients
      who did not take medication showed higher TNFalpha levels compared to healthy
      controls. In conclusion, we suggest that inflammatory pathways that involve IL
      12p70 or TNFalpha are important to the pathogenesis of TD.

PMID- 27886580
TI  - The real-life effectiveness of psychosocial therapies on social autonomy in
      schizophrenia patients: Results from a nationwide cohort study in France.
AB  - The objectives of the present study were to describe the prescribing patterns for
      psychosocial therapies in routine clinical practice and to assess the impact of
      psychoeducation on symptoms and social autonomy of patients with schizophrenia.
      We used data from the nationwide French ESPASS observational cohort study
      including 5967 patients with schizophrenia, which provided data on exposure to
      psychosocial therapies from 4961 (83%) participants. Patients who initiated
      psychosocial therapy within the first 3 months of study onset (n=143) were
      compared to patients not subject to psychosocial therapy throughout follow up
      (n=4268), using parametric tests. Symptom severity and social autonomy at 6
      months from baseline were compared between patients undergoing psychoeducation
      (n=117) and patients not subject to psychosocial therapy, matched (1:1) on
      propensity scores. Patients who initiated psychosocial therapy were significantly
      younger, more severely ill and used less often antipsychotic drugs than patients
      in the reference group. At 6 months, patients who initiated psychoeducation and
      their matched referents did not differ significantly in terms of symptom
      severity, but their level of improvement in social autonomy was significantly
      greater (p=0.005). In routine clinical practice, psychoeducation in addition to
      antipsychotic drugs provides some benefit among schizophrenia patients,
      particularly in terms of social autonomy.

PMID- 27886581
TI  - A multi-omic approach to elucidate low-dose effects of xenobiotics in zebrafish
      (Danio rerio) larvae.
AB  - Regulatory-approved toxicity assays such as the OECD Fish Embryo Toxicity Assay
      (TG236) allow correlation of chemical exposure to adverse morphological
      phenotypes. However, these assays are ineffective in assessing sub-lethal (i.e.
      low-dose) effects, or differentiating between similar phenotypes induced by
      different chemicals. Inclusion of multi-omic analyses in studies investigating
      xenobiotic action provides improved characterization of biological response,
      thereby enhancing prediction of toxicological outcomes in whole animals in the
      absence of morphological effects. In the current study, we assessed perturbations
      in both the metabolome and transcriptome of zebrafish (Danio rerio; ZF) larvae
      exposed from 96 to 120h post fertilization to environmental concentrations of
      acetaminophen (APAP), diphenhydramine (DH), carbamazepine (CBZ), and fluoxetine
      (FLX); common pharmaceuticals with known mechanisms of action. Multi-omic
      responses were evaluated independently and integrated to identify molecular
      interactions and biological relevance of the responses. Results indicated
      chemical- and dose-specific changes suggesting differences in the time scale of
      transcript abundance and metabolite production. Increased impact on the
      metabolome relative to the transcriptome in FLX-treated animals suggests a
      stronger post-translational effect of the treatment. In contrast, the
      transcriptome showed higher sensitivity to perturbation in DH-exposed animals.
      Integration of 'omic' responses using multivariate approaches provided additional
      insights not obtained by independent 'omic' analyses and demonstrated that the
      most distinct overall response profiles were induced following low-dose exposure
      for all 4 pharmaceuticals. Importantly, changes in transcript abundance
      corroborated with predictions from metabolomic enrichment analyses and the
      identified perturbed biological pathways aligned with known xenobiotic mechanisms
      of action. This work demonstrates that a multi-omic toxicological approach,
      coupled with a sensitive animal model such as ZF larvae, can help characterize
      the toxicological relevance of acute low-dose chemical exposures.

PMID- 27886582
TI  - Crude extract of cyanobacteria (Radiocystis fernandoi, strain R28) induces liver
      impairments in fish.
AB  - Radiocystis fernandoi R28 strain is a cyanobacterium which produces mostly the RR
      and YR microcystin variants (MC-RR and MC-YR, respectively). The effects of crude
      extract of the R. fernandoi strain R28 were evaluated on the protein phosphatases
      and on the structure and ultrastructure of the liver of the Neotropical fish,
      Hoplias malabaricus, after acute and subchronic exposure. Concomitantly, the
      accumulation of the majority of MCs was determined in the liver and muscle. The
      fish were exposed to 120.60 MC-RR+MC-LR kg-fish-1 (=100MUg MC-LReq kg-fish-1) for
      12 and 96h (one single dose, acute exposure) and 30days (one similar dose every
      72h, subchronic exposure). MCs did not accumulate in the muscle but, in the
      liver, MC-YR accumulated after acute exposure and MC-RR and MC-YR accumulation
      occurred after subchronic exposure. Protein phosphatase 2A (PP2A) activity was
      inhibited only after subchronic exposure. Acute exposure induced liver hyperemia,
      hemorrhage, changes in hepatocytes and cord-like disorganization. At the
      ultrastructural level, the decreasing of glycogen and lipid levels, the swelling
      of mitochondria and whirling of endoplasmic reticulum suggested hepatocyte
      necrosis. Subchronic exposure resulted in a complete disarrangement of cord-like
      hepatocytes, some recovery of mitochondria and whirling endoplasmic reticulum and
      extensive connective tissues containing fibrous materials in the liver
      parenchyma. Despite microcystin toxicity and liver alterations, no tumor was
      induced by MCs. In conclusion, the increased algal mass of R. fernandoi in
      tropical freshwater, producing mainly MC-RR and MC-YR variants, results in fish
      liver impairments.

PMID- 27886583
TI  - Bioaugmentation and rhizosphere-assisted biodegradation as strategies for
      optimization of the dissipation capacity of biobeds.
AB  - Biobeds are on-farm biodepuration systems whose efficiency rely on their high
      pesticide biodegradation capacity. We evaluated two optimization strategies,
      bioaugmentation and/or rhizosphere-assisted biodegradation, to maximize the
      dissipation capacity of biobeds. Iprodione was used as a model pesticide. Its
      dissipation and metabolism was determined in a biobed packing material inoculated
      with an iprodione-degrading Arthrobacter strain C1 (bioaugmentation, treatments
      B+C1) and/or seeded with ryegrass (rhizosphere-assisted biodegradation,
      treatments B+P). The impact of those strategies on the activity and composition
      of the microbial community was determined. Bioaugmentation accelerated the
      dissipation of iprodione which was further enhanced in the bioaugmented,
      rhizosphere-assisted treatment (treatment B+P+C1, Half-life (DT50) = 3.4 d),
      compared to the non-bioaugmented, non rhizosphere-assisted control (DT50 = 9.5 d,
      treatment B). Bioaugmentation resulted in the earlier formation of intermediate
      formation of metabolites I (3,5-dichlorophenyl-carboxamide), II (3,5
      dichlorophenylurea acetate) and 3,5-dichloroaniline (3,5-DCA). The latter was
      further dissipated by the indigenous microbial community. Acid phosphatase (AP)
      and beta-glucosidase (GLU) were temporarily stimulated in rhizosphere-assisted
      treatments, whereas a stimulation of the fluorescein diacetate (FDA) hydrolytic
      activity in the bioaugmented treatments coincided with the hydrolysis of
      iprodione. q-PCR showed that changes in the abundance of alpha-proteobacteria and
      firmicutes was driven by the presence of rhizosphere while bioaugmentation had no
      significant effect.

PMID- 27886584
TI  - Attributes of successful actions to restore lakes and estuaries degraded by
      nutrient pollution.
AB  - As more success is achieved in restoring lakes and estuaries from the impacts of
      nutrient pollution, there is increased opportunity to evaluate the scientific,
      social, and policy factors associated with achieving restoration goals. We
      examined case studies where deliberate actions to reduce nutrient pollution and
      restore ecosystems resulted in ecological recovery. Prospective cases were
      identified from scientific literature and technical documents for lakes and
      estuaries with: (1) scientific evidence of nutrient pollution; (2) restoration
      actions taken to mitigate nutrient pollution; and (3) documented ecological
      improvement. Using these criteria, we identified 9 estuaries and 7 lakes spanning
      countries, climatic regions, physical types, depths, and watershed areas. Among
      16 case studies ultimately included, 8 achieved improvements short of stated
      restoration goals. Five more were successful initially, but condition
      subsequently declined. Three of the case studies achieved their goals fully and
      are currently managing to maintain the restored condition. We examined each case
      to identify both common attributes of nutrient management, grouped into 'themes',
      and variations on those attributes, which were coded into categorical variables
      based on thorough review of documents associated with each case. The themes and
      variables were organized into a broad conceptual model illustrating how they
      relate to each other and to nutrient management outcomes. We then explored
      relationships among the themes and variables using multiple correspondence
      analysis (MCA). Results of the MCA suggested that the attributes most associated
      with achieving restoration goals include: (1) leadership by a dedicated watershed
      management agency; (2) governance through a bottom-up collaborative process; (3)
      a strategy that set numeric targets based on a specific ecological goal; and (4)
      actions to reduce nutrient loads from all sources. While our study did not
      provide a comprehensive road map to successful nutrient management, it suggested
      attributes that could be emulated in future efforts. The quantitative approach
      that was applied could be used to provide ongoing analysis as new examples of
      nutrient management success emerge.

PMID- 27886585
TI  - Facilitating adaptive management in a government program: A household energy
      efficiency case study.
AB  - Interim evaluations of government programs can sometimes reveal lower than
      expected outcomes, leading to the question of how adjustments can be made while
      the program is still underway. Although adaptive management frameworks can
      provide a practical roadmap to address this question, a lack of successful
      learnings and poor implementation have hampered the progress and wider
      application of adaptive management. Using a case study involving an energy
      efficiency government program targeting low-income households, this article
      provides supporting evidence on how adaptive management can be facilitated and
      applied. Factors such as proactive and responsive leadership, establishing a
      research-practice interface, and recognizing the skills, expertise, and
      contributions of multiple stakeholders guided adjustments to the program, and
      later paved the way for longer-term organizational learning that impacted how
      other programs are delivered. Implications for knowledge and practice, and a
      discussion of the challenges faced in the program, advance current thinking in
      adaptive management.

PMID- 27886586
TI  - Nitrous oxide from moving bed based integrated fixed film activated sludge
      membrane bioreactors.
AB  - The present paper reports the results of a nitrous oxide (N2O) production
      investigation in a moving bed based integrated fixed film activated sludge (IFAS)
      membrane bioreactor (MBR) pilot plant designed in accordance with the University
      of Cape Town layout for biological phosphorous removal. Gaseous and liquid
      samples were collected in order to measure the gaseous as well as the dissolved
      concentration of N2O. Furthermore, the gas flow rate from each reactor was
      measured and the gas flux was estimated. The results confirmed that the anoxic
      reactor represents the main source of nitrous oxide production. A significant
      production of N2O was, however, also found in the anaerobic reactor, thus
      indicating a probable occurrence of the denitrifying phosphate accumulating
      organism activity. The highest N2O fluxes were emitted from the aerated reactors
      (3.09 g N2ON m-2 h-1 and 9.87 g N2ON m-2 h-1, aerobic and MBR tank,
      respectively). The emission factor highlighted that only 1% of the total treated
      nitrogen was emitted from the pilot plant. Furthermore, the measured N2O
      concentrations in the permeate flow were comparable with other reactors. Nitrous
      oxide mass balances outlined a moderate production also in the MBR reactor
      despite the low hydraulic retention time. On the other hand, the mass balance
      showed that in the aerobic reactor a constant consumption of nitrous oxide (up to
      almost 15 mg N2O h-1) took place, due to the high amount of stripped gas.

PMID- 27886587
TI  - Measures of readiness for cognitive behavioural therapy in people with
      intellectual disability: A systematic review.
AB  - BACKGROUND AND AIMS: Cognitive behavioural therapy (CBT) is a promising treatment
      for mental health problems in people with intellectual disabilities but some may
      not be suited or ready. This review critically evaluates the quality and utility
      of measures of CBT readiness in people with intellectual disabilities. METHODS
      AND PROCEDURES: Twelve studies of six measures based on three aspects of CBT
      readiness were identified through systematic review. OUTCOMES AND RESULTS: Across
      measures, measurement quality was largely poor or un-assessed. Only one study
      evaluated measurement change over the course of CBT. Not all participants with
      intellectual disabilities could 'pass' readiness measures and performance may be
      affected by levels of language and cognitive functioning. There was some evidence
      that CBT readiness is trainable with brief interventions. CONCLUSIONS AND
      IMPLICATIONS: Before using readiness measures in a clinical context, further work
      is needed to extend initial evidence on recognising cognitive mediation as a CBT
      readiness ability. Given the lack of consensus as to the definition of CBT
      readiness and the heterogeneity of CBT interventions, future research could also
      focus on developing readiness measures using a bottom up approach, developing
      measures within the context of CBT interventions themselves, before further
      refining and establishing their psychometric properties. WHAT THIS PAPER ADDS:
      This paper is the first to systematically review measures of skills thought
      necessary to be ready for cognitive behavioural therapy in intellectual
      disabilities. The findings suggest that while readiness skills may be trainable
      with brief interventions, the available measures of these skills have not been
      fully evaluated for quality. Levels of functioning on these measures have yet to
      be established relative to those without intellectual disabilities and
      critically, there is very little evidence as to whether these skills are
      important in cognitive behavioural therapy process and outcome. We suggest that
      future research could focus on those constructs where there is preliminary
      evidence for utility such as recognising cognitive mediation and also on
      developing the concept of readiness perhaps by developing measures within the
      context of specific CBT interventions. Until this is done, clinicians should
      exercise caution in using these measures to assess readiness for cognitive
      behavioural therapy in people with intellectual disabilities.

PMID- 27886588
TI  - The expanding role of stereotactic body radiation therapy in oligometastatic
      solid tumors: What do we know and where are we going?
AB  - The spectrum hypothesis posits that there are distinct clinical states of
      metastatic progression. Early data suggest that aggressive treatment of more
      biologically indolent metastatic disease, characterized by metastases limited in
      number and destination organ, may offer an opportunity to alter the disease
      course, potentially allowing for longer survival, delay of systemic therapy, or
      even cure. The development of stereotactic body radiation therapy (SBRT) has
      opened new avenues for the treatment of oligometastatic disease. Early data
      support the use of SBRT for treating oligometastases in a number of organs, with
      promising rates of treated metastasis control and overall survival. Ongoing
      investigation is required to definitively establish benefit, determine the
      appropriate treatment regimen, refine patient selection, and incorporate SBRT
      with systemic therapies.

PMID- 27886589
TI  - ESR1 mutations: Moving towards guiding treatment decision-making in metastatic
      breast cancer patients.
AB  - Mutations in the gene coding for the estrogen receptor (ER), ESR1, have been
      associated with acquired endocrine resistance in patients with ER-positive
      metastatic breast cancer (MBC). Functional studies revealed that these ESR1
      mutations lead to constitutive activity of the ER, meaning that the receptor is
      active in absence of its ligand estrogen, conferring resistance against several
      endocrine agents. While recent clinical studies reported that the occurrence of
      ESR1 mutations is rare in primary breast cancer tumors, these mutations are more
      frequently observed in metastatic tissue and circulating cell-free DNA of MBC
      patients pretreated with endocrine therapy. Given the assumed impact that the
      presence of ESR1 mutations has on outcome to endocrine therapy, assessing ESR1
      mutations in MBC patients is likely to be of significant interest to further
      individualize treatment for MBC patients. Here, ESR1 mutation detection methods
      and the most relevant pre-clinical and clinical studies on ESR1 mutations
      regarding endocrine resistance are reviewed, with particular interest in the
      ultimate goal of guiding treatment decision-making based on ESR1 mutations.

PMID- 27886591
TI  - Gambling machine annexes as enabling spaces for addictive engagement.
AB  - The widespread proliferation of electronic gambling machines and improvements to
      their design have contributed to rising levels of gambling-related harm including
      harms associated with addictive behaviour and other impacts on health and
      wellbeing. Research into their addictive potential has focused mainly on the
      interface between gamblers and the machines themselves. We shift the focus onto
      the spatial contexts, the rooms and the venues, in which gambling machines are
      positioned. By examining a series of common layouts we identify the division of
      venues into two main areas: one for the main social activities of the venue (the
      "main hall") and the other a partitioned area (the "annex") in which gambling
      machines are tightly clumped in ways that discourage social interaction. Other
      features of the annex that encourage uninterrupted and solitary play include the
      absence of tables to socialize around, dimmed lighting and entry pathways that
      minimize scrutiny. We argue that these features promote a style of play more
      oriented towards heavy and problematic gambling. We also explore explanations for
      the nature of these annexes and discuss implications for public health.

PMID- 27886590
TI  - Pelvic floor dynamics during high-impact athletic activities: A computational
      modeling study.
AB  - BACKGROUND: Stress urinary incontinence is a significant problem in young female
      athletes, but the pathophysiology remains unclear because of the limited
      knowledge of the pelvic floor support function and limited capability of
      currently available assessment tools. The aim of our study is to develop an
      advanced computer modeling tool to better understand the dynamics of the internal
      pelvic floor during highly transient athletic activities. METHODS: Apelvic model
      was developed based on high-resolution MRI scans of a healthy nulliparous young
      female. A jump-landing process was simulated using realistic boundary conditions
      captured from jumping experiments. Hypothesized alterations of the function of
      pelvic floor muscles were simulated by weakening or strengthening the levator ani
      muscle stiffness at different levels. Intra-abdominal pressures and corresponding
      deformations of pelvic floor structures were monitored at different levels of
      weakness or enhancement. FINDINGS: Results show that pelvic floor deformations
      generated during a jump-landing process differed greatly from those seen in a
      Valsalva maneuver which is commonly used for diagnosis in clinic. The urethral
      mobility was only slightly influenced by the alterations of the levator ani
      muscle stiffness. Implications for risk factors and treatment strategies were
      also discussed. INTERPRETATION: Results suggest that clinical diagnosis should
      make allowances for observed differences in pelvic floor deformations between a
      Valsalva maneuver and a jump-landing process to ensure accuracy. Urethral
      hypermobility may be a less contributing factor than the intrinsic sphincteric
      closure system to the incontinence of young female athletes.

PMID- 27886592
TI  - The intersection of climate/environment, food, nutrition and health: crisis and
      opportunity.
AB  - Climate/environmental change (C-E-C) is affecting human health and quality of
      life. Significant attention has been given to the impact of C-E-C on food supply,
      and food as a vehicle for exposure. However, C-E-C has been superimposed on
      prevalent malnutrition, infectious and non-communicable diseases. We discuss why
      nutrition is not synonymous with food and must be viewed as a biological variable
      that affects and is affected by both C-E-C as well as the current global health
      challenges. The nexus of C-E-C, food, nutrition and health must be considered in
      the development of safe and efficacious interventions. A case is presented for
      how the convergence of C-E-C, food/nutrition and health, presents an opportunity
      for more integrated approaches to achieve global health goals.

PMID- 27886594
TI  - Proposed binding mechanism of galbanic acid extracted from Ferula assa-foetida to
      DNA.
AB  - Recently, galbanic acid (GA), a sesquiterpenoid coumarin, has been introduced as
      an apoptotic and geno/cytotoxicity agent. In the present study, GA has been
      extracted from Ferula assa-foetida, a native medicinal plant in Iran, and
      characterized by 1H NMR, mass spectroscopy. Additionally, spectroscopic studies
      have been performed in order to investigate its DNA-interaction mode. The
      electrochemical behavior of GA has been studied by cyclic voltammetry (CV) in
      various scan rates. In neutral media (pH=7.3) one irreversible cathodic peak was
      obtained at -1.46 V, while in higher scan rates an irreversible one was
      determined at -1.67 V. According to the voltametric data GA can be easily reduced
      by 2e-/2H+ mechanism at hanging mercury drop electrode (HMDE). The interaction of
      GA with ct-DNA was evaluated by CV, differential pulse voltammetry (DPV),
      enhancement fluorescence, UV-Vis, FT-IR spectroscopy and molecular docking. The
      molecular docking study shows that the GA interacts to DNA on partial
      intercalation mode via DNA groove binding and forms a complex by van der Waals
      and electroastatic interactions. In addition, the thermodynamic parameters of GA
      DNA complex were investigated with DeltaH degrees , DeltaS degrees  and DeltaG
      degrees  values of 15.81KJmol-1, 133.95Jmol-1 and -23.10KJmol-1, respectively.
      All data revealed that the GA is binding to DNA by van der Waals and
      electrostatic interactions through the partial intercalations from the DNA's
      grooves.

PMID- 27886593
TI  - The evolution of microRNAs in plants.
AB  - MicroRNAs (miRNAs) are a central player in post-transcriptional regulation of
      gene expression and are involved in numerous biological processes in eukaryotes.
      Knowledge of the origins and divergence of miRNAs paves the way for a better
      understanding of the complexity of the regulatory networks that they participate
      in. The biogenesis, degradation, and regulatory activities of miRNAs are
      relatively better understood, but the evolutionary history of miRNAs still needs
      more exploration. Inverted duplication of target genes, random hairpin sequences
      and small transposable elements constitute three main models that explain the
      origination of miRNA genes (MIR). Both inter-species and intra-species divergence
      of miRNAs exhibits functional adaptation and adaptation to changing environments
      in evolution. Here we summarize recent progress in studies on the evolution of
      MIR and related genes.

PMID- 27886595
TI  - Synthesis, photophysical properties and systematic evaluations of new
      phenanthroimidazole fluorescent probe for bioimaging: Experimental and
      theoretical study.
AB  - In this study, the newly synthesized 4'-(1H-phenantro[9,10-d]-imidazol-2-yl)
      bifenyl-4-carboaldehyde - PB2 was investigated as a fluorescent dye. For this
      reason, the spectroscopic properties in solvents of different polarity were
      studied. The experimental data were supported by quantum-chemical calculations
      using density functional theory. Measurements and theoretical calculations showed
      that PB2 compound is characterized by the non-monotonic solvatochromism, strongly
      polar charge transfer excited state, large Stokes' shift, high fluorescence
      quantum yield and high fluorescence lifetime. Simulations using AutoDock
      presented in this study, showed that after conjugation with Concanavalin A in the
      active site with LYS200, the PB2 possesses the highest probability of binding
      affinity. Circular dichroism (CD) measurement was performed to monitor the
      changes of the secondary structure of Concanavalin A induced by the presence of
      PB2 fluorophore. These results indicate that the addition of PB2 influences the
      secondary structure of Concanavalin A, but does not affect the interactions with
      carbohydrate moieties. Finally, by using fluorescence microscopy it was
      demonstrated that the PB2 is the photostable fluorescent probe and PB2 conjugate
      Concanavalin A exhibits a blue fluorescence. The results of this study have
      implications in designing PB2-protein conjugate as a valuable alternative to
      commercial probes designed for cellular labeling in biological and biomedical
      research.

PMID- 27886596
TI  - An end-point method based on graphene oxide for RNase H analysis and inhibitors
      screening.
AB  - As a highly conserved damage repair protein, RNase H can hydrolysis DNA-RNA
      heteroduplex endonucleolytically and cleave RNA-DNA junctions as well. In this
      study, we have developed an accurate and sensitive RNase H assay based on
      fluorophore-labeled chimeric substrate hydrolysis and the differential affinity
      of graphene oxide on RNA strand with different length. This end-point measurement
      method can detect RNase H in a range of 0.01 to 1 units /mL with a detection
      limit of 5.0*10-3 units/ mL under optimal conditions. We demonstrate the utility
      of the assay by screening antibiotics, resulting in the identification of
      gentamycin, streptomycin and kanamycin as inhibitors with IC50 of 60+/-5uM, 70+/
      8uM and 300+/-20uM, respectively. Furthermore, the assay was reliably used to
      detect RNase H in complicated biosamples and found that RNase H activity in tumor
      cells was inhibited by gentamycin and streptomycin sulfate in a concentration
      dependent manner. The average level of RNase H in serums of HBV infection group
      was similar to that of control group. In summary, the assay provides an
      alternative tool for biochemical analysis for this enzyme and indicates the
      feasibility of high throughput screening inhibitors of RNase H in vitro and in
      vivo.

PMID- 27886597
TI  - Paper-based enzymatic electrode with enhanced potentiometric response for
      monitoring glucose in biological fluids.
AB  - A novel paper-based potentiometric sensor with an enhanced response for the
      detection of glucose in biological fluids is presented. The electrode consists on
      platinum sputtered on a filter paper and a Nafion membrane to immobilize the
      enzyme glucose oxidase. The response obtained is proportional to the logarithm of
      the concentration of glucose, with a sensitivity of -119+/-8mV.decade-1, a linear
      range that spans from 10-4M to 10-2.5 M and a limit of detection of 10-4.5 M of
      glucose. It is shown that Nafion increases the sensitivity of the technique while
      minimizing interferences. Validation with human serum samples shows an excellent
      agreement when compared to standard methods. This approach can become an
      interesting alternative for the development of simple and affordable devices for
      point of care and home-based diagnostics.

PMID- 27886598
TI  - A fluorescent probe for the efficient discrimination of Cys, Hcy and GSH based on
      different cascade reactions.
AB  - A fluorescent probe (1) for distinguishing amongst biothiols, including cysteine
      (Cys), homocysteine (Hcy) and glutathione (GSH), is developed based on different
      cascade reactions. The key design feature of fluorescent probe 1 is the
      integration of two potential reaction groups for the thiol and amino groups of
      biothiols in one molecule. By reacting with the halogen atom and alpha, beta
      unsaturated malonitrile in probe 1, Cys, Hcy and GSH can generate a total of
      three main products with distinct photophysical properties. Probe 1 shows a
      strong fluorescence turn-on response to Cys with blue-green emission by using an
      excitation wavelength of 390nm. At an excitation wavelength of 500nm, probe 1
      responds to GSH over Cys and Hcy and emits strong orange fluorescence. The
      discrimination of biothiols can be demonstrated by cell imaging experiments,
      indicating that probe 1 can be a useful tool for the selective imaging of Cys and
      GSH in living cells.

PMID- 27886600
TI  - A lifetime-sensitive fluorescence anisotropy probe for DNA-based bioassays: The
      case of SYBR Green.
AB  - In standard steady-state fluorescence anisotropy (FA) DNA-based assays, the
      ligand binding to a given receptor is typically signalled by the rotational
      correlation time changes of the tracer. Herein, we report a radically different
      strategy that relies on the peculiar excited state lifetime features of the SYBR
      Green (SG) dye. This DNA-binding probe exhibits a drastically short lifetime in
      solution, leading to a high FA signal. Its complexation to oligonucleotides
      determines a singular and very large depolarization depending on the concerted
      effects of extreme lifetime enhancement and resonance energy homotransfer. On the
      basis of ligand-induced changes in the molar fractions of bound and free forms of
      SG, the approach provides an unprecedented means for the FA monitoring of the
      ligand binding to short DNA molecules, allowing the elaboration of a variety of
      intercalator displacement assays and label-free biosensors that involve diverse
      DNA structures (duplex, hairpin, G-quadruplex and single-stranded), ligand types
      (ion, small organic molecule and protein) and binding modes (intercalation, minor
      groove, allosteric switch). These findings open up promising avenues in the
      design of a new generation of FA assays.

PMID- 27886599
TI  - Recent advances in DNA-based electrochemical biosensors for heavy metal ion
      detection: A review.
AB  - The presence of heavy metal in food chains due to the rapid industrialization
      poses a serious threat on the environment. Therefore, detection and monitoring of
      heavy metals contamination are gaining more attention nowadays. However, the
      current analytical methods (based on spectroscopy) for the detection of heavy
      metal contamination are often very expensive, tedious and can only be handled by
      trained personnel. DNA biosensors, which are based on electrochemical
      transduction, is a sensitive but inexpensive method of detection. The principles,
      sensitivity, selectivity and challenges of electrochemical biosensors are
      discussed in this review. This review also highlights the major advances of DNA
      based electrochemical biosensors for the detection of heavy metal ions such as
      Hg2+, Ag+, Cu2+ and Pb2+.

PMID- 27886601
TI  - One-step separation-free detection of carcinoembryonic antigen in whole serum:
      Combination of two-photon excitation fluorescence and optical trapping.
AB  - Direct analysis of biomolecules in complex biological samples remains a major
      challenge for fluorescence-based approaches due to the interference of background
      signals. Herein, we report an analytical methodology by exploiting a single low
      cost near-infrared sub-nanosecond pulse laser to synchronously actualize optical
      trapping and two-photon excitation fluorescence for senstive detection of
      carcinoembryonic antigen (CEA) in buffer solution and human whole serum with no
      separation steps. The assay is performed by simultaneously trapping and exciting
      the same immune-conjugated microsphere fabricated with a sandwich immunization
      strategy. Since the signal is strictly limited in the region of a three
      dimensional focal volume where the microsphere is trapped, no obvious background
      signal is found to contribute the detected signals and thus high signal-to
      background data are obtained. As a proof-of-concept study, the constructed
      platform exhibits good specificity for CEA and the detection limit reaches as low
      as 8pg/mL (45 fM) with a wide linear range from 0.01 to 60ng/mL in the both
      cases. To investigate the potential application of this platform in clinical
      diagnosis, 15 cases of serum samples were analyzed with satisfactory results,
      which further confirm the applicability of this method.

PMID- 27886602
TI  - Multifunctional nanoparticles for protein detections in thin channels.
AB  - This paper presents a method for simultaneous detection of two proteins by using
      multifunctional nanoparticles with a magnetic immunoassay in thin channels.
      Biofunctional magnetic graphene quantum dots (GQDs) combined with two
      biofunctional quantum dots (QDs) were used for simultaneously detecting two
      proteins. Magnetic GQDs enabled selective and quantitative nanoparticle
      deposition with blue emission. Biofunctional QDs confirmed the two protein
      detections with orange and green emissions. We used two model biomarkers [alpha
      fetoprotein (AFP) and cancer antigen 125 (CA125)] to demonstrate the feasibility
      of the proposed method. The detection limits (0.06pg/mL AFP and 0.001U/mL CA125)
      and linear ranges (0.2pg/mL-0.68ng/mL AFP and 0.003-25U/mL CA125) of this method
      are the same as those of single protein detection within experimental errors.
      These detection limits are substantially lower and the linear ranges are
      considerably wider than those of enzyme-linked immunosorbent assay (ELISA) and
      other immunoassay methods. The differences between the proposed method and an
      ELISA method in AFP and CA125 measurements of serum samples were less than 12%.
      The proposed method demonstrates favorable detection of biomarkers with
      advantages of speed, sensitivity, selectivity, and throughput.

PMID- 27886603
TI  - MnO2 nanosheets as an artificial enzyme to mimic oxidase for rapid and sensitive
      detection of glutathione.
AB  - Nanozymes are increasingly used as components in assays and diagnostics. Here, we
      describe a rapid and highly sensitive colorimetric assay for the detection and
      quantification of glutathione (GSH) employing MnO2 nanosheets as an artificial
      oxidase. In the assay pale yellow 3,3',5,5'-tetramethylbenzidine (TMB) is
      oxidized to a blue product (oxTMB) under catalyzing of MnO2 nanosheets with a
      significant change in absorption at 650nm. GSH selectively inhibits this reaction
      with a detection limit of 300nM. The high specificity of inhibition by GSH allows
      this system to be used to determine the GSH concentrations in human serum
      samples. The MnO2 nanosheet-based assay is simple, rapid, sensitive and selective
      for the quantification of GSH and surpasses detection methods based on other MnO2
      nanomaterials.

PMID- 27886604
TI  - A low cost and palm-size analyzer for rapid and sensitive protein detection by AC
      electrokinetics capacitive sensing.
AB  - Specific detection of protein biomarkers has a wide range of applications in
      areas such as medical science, diagnostics, and pharmacology. Quantitative
      detection of protein biomarkers in biological media, such as serum, is critically
      important in detecting disease or physiological malfunction, or tracking disease
      progression. Among various detection methods, electrical detection is
      particularly well suited for point-of-care (POC) specific protein detection,
      being of low cost, light weight and small form factor. A portable system for
      sensitive and quantitative detection of protein biomarkers will be highly
      valuable in controlling and preventing diseases outbreaks. Recently, an
      alternating current electrokinetic (ACEK) capacitive sensing method has been
      reported to demonstrate very promising performance on rapid and sensitive
      detection of specific protein from serum. In this work, a low cost and portable
      analyzer with good accuracy is developed to use with ACEK capacitive sensing to
      produce a true POC technology. The development of a board-level capacitance
      readout system is presented, as well as the adaption of the protocol for use with
      ACEK capacitive sensing. Results showed that the developed system could achieve a
      limit of detection of 10ng/mL, comparable to a sophisticated benchtop instrument.
      With its small size and light-weight similar to a smart phone, the developed
      system is ready to be applicable to POC diagnostics. Further, the readout system
      can be readily expanded for multichannel monitoring and telecommunication
      capabilities.

PMID- 27886605
TI  - Self-tuning interfacial architecture for Estradiol detection by surface plasmon
      resonance biosensor.
AB  - This study reports the operation principles for reusable SPR biosensors utilizing
      nanoscale-specific electrostatic levitation phenomena in their sensitive layer
      design. Functional macromolecular building blocks localized near the "charged"
      surface by a variety of weak electrostatic interactions create a flexible and
      structurally variable architecture. A proof-of-concept is demonstrated by an
      immunospecific detection of 17beta-Estradiol (E2) following the competitive
      inhibition format. The sensing interfacial architecture is based on the BSA-E2
      conjugate within the BSA matrix immobilized on the "charged" (as a result of
      guanidine thiocyanate treatment) gold surface at pH 5.0. Kinetic analysis for
      different E2 concentrations shows that using parameter beta of the stretched
      exponential function ~(1-exp(-(t/tau)beta) as an analyte-specific response
      measure allows one to substantially decrease the low detection limit (down to 10
      3ng/ml) and increase the dynamic range (10-3-103ng/ml) of the SPR biosensor.
      Finally, it's concluded that the created interfacial architecture is a typical
      complex system, where SPR response is formed by the stochastic interactions
      within the whole variety of processes in the system. The E2 addition destroys the
      uniformity of the reaction space (where an interaction of the antibody (Ab) and
      the analog of E2 in the self-tuneable matrix takes place) by the redistribution
      of the immunospecific complexes Ab(E2)x (x=0, 1, 2) dependent on E2
      concentration. Binding dynamics changes are reflected in the values of beta which
      summarize in compact form all "hidden" information specific for the evolving
      distributed interfacial system.

PMID- 27886606
TI  - A symmetric supercapacitor/biofuel cell hybrid device based on enzyme-modified
      nanoporous gold: An autonomous pulse generator.
AB  - The integration of supercapacitors with enzymatic biofuel cells (BFCs) can be
      used to prepare hybrid devices in order to harvest significantly higher power
      output. In this study, a supercapacitor/biofuel cell hybrid device was prepared
      by the immobilisation of redox enzymes with electrodeposited poly(3,4
      ethylenedioxythiophene) (PEDOT) and the redox polymer [Os(2,2'
      bipyridine)2(polyvinylimidazole)10Cl]+/2+(Os(bpy)2PVI) on dealloyed nanoporous
      gold. The thickness of the deposition layer can be easily controlled by tuning
      the deposition conditions. Once charged by the internal BFC, the device can be
      discharged as a supercapacitor at a current density of 2mAcm-2 providing a
      maximum power density of 608.8MUWcm-2, an increase of a factor of 468 when
      compared to the power output from the BFC itself. The hybrid device exhibited
      good operational stability for 50 charge/discharge cycles and ca. 7h at a
      discharge current density of 0.2mAcm-2. The device could be used as a pulse
      generator, mimicking a cardiac pacemaker delivering pulses of 10MUA for 0.5ms at
      a frequency of 0.2Hz.

PMID- 27886607
TI  - Preparation of the tri-arabino di-mycolate fragment of mycobacterial
      arabinogalactan from defined synthetic mycolic acids.
AB  - An efficient synthetic approach to tri-arabino di-mycolates, using structurally
      defined synthetic alpha-, keto and methoxy mycolic acids is described.

PMID- 27886608
TI  - Changes of normal appearing optic nerve head on diffusion-weighted imaging in
      patients with diabetic retinopathy.
AB  - PURPOSE: To investigate whether there is any change by measuring ADC values
      particularly of the optic nerve head (ONH) in patients with diabetic retinopathy
      (DR). MATERIAL AND METHODS: ADC values at the ONHs was measured in 56 patients
      and 68 controls. RESULTS: ADC values of ONHs were significantly higher in
      patients with DR compared to controls (p=0.011). ADC values in patients with
      macular edema were higher than those without macular edema (p=0.017). CONCLUSION:
      DWI of ONHs can be useful in cases where it is difficult to assess macular edema
      during fundus examination, especially in diabetic patients with cataract.

PMID- 27886609
TI  - Utility of virtual touch quantification in the diagnosis of pancreatic ductal
      adenocarcinoma.
AB  - This study aimed to compare the tissue stiffness of pancreatic ductal
      adenocarcinoma (PDAC) with that of pancreatic parenchyma using virtual touch
      quantification (VTQ). SWV was measured in 34 PDAC lesions and in pancreatic
      parenchyma of both controls and patients. SWVs in PDAC lesions were significantly
      higher than in pancreatic parenchyma in both healthy controls and in patients
      with PDAC. The area under the ROC for diagnosis of PDAC was 0.94 for pancreatic
      parenchyma in healthy controls, and 0.85 for pancreatic parenchyma in patients
      with PDAC. VTQ can provide a useful and additional information for diagnosis of
      PDAC.

PMID- 27886610
TI  - Integration of intracardiac echocardiography and computed tomography during
      atrial fibrillation ablation: Combining ultrasound contours obtained from the
      right atrium and ventricular outflow tract.
AB  - BACKGROUND: We aimed to optimize the acquisition of the left atrial (LA) and
      pulmonary vein (PV) ultrasound contours for more accurate integration of
      intracardiac echocardiography (ICE) and computed tomography (CT) using the
      CARTO(r) 3 system during atrial fibrillation (AF) ablation. METHODS: Eighty-five
      AF patients underwent integration of ICE and CT using (1) the LA roof and
      posterior wall contours acquired from the right atrium (RA), (2) all LA/PV
      contours from the RA (Whole-RA-integration), (3) the LA roof/posterior wall
      contours from the RA and right ventricular outflow tract (RVOT) (Posterior-RA/RV
      integration), and (4) all LA/PV contours from the RA and RVOT (Whole-RA/RV
      integration). The integration accuracy was compared using the (1) surface
      registration error, (2) distances between the three-dimensional CT and eight
      specific sites on the anterior, posterior, superior, and inferior aspects of the
      right and left circumferential PV isolation lines, and (3) registration score: a
      score of 0 or 1 was assigned for whether or not each specific site was visually
      aligned with the CT, and summed for each method (0 best, 8 worst). RESULTS:
      Posterior-RA/RV-integration revealed a significantly lower surface registration
      error (1.30+/-0.15mm) than Whole-RA- and Whole-RA/RV-integration (p<0.001). The
      mean distances of the eight specific sites and the registration score for
      Posterior-RA/RV-integration (median 1.26mm and 2, respectively) were
      significantly smaller than those for the other integration approaches (p<0.001).
      CONCLUSIONS: Image integration with the LA roof and posterior wall contours
      acquired from the RA and RVOT may provide greater accuracy for catheter
      navigation with three-dimensional CT during AF ablation.

PMID- 27886611
TI  - Inter- and intraobserver consistency in LV myocardial strain measurement using a
      novel multi-layer technique in patients with severe aortic stenosis and preserved
      LV ejection fraction.
AB  - BACKGROUND: A new transthoracic echocardiography (TTE) technique allows multi
      layer measurement of left ventricular (LV), endocardial, epicardial, and whole
      layer myocardial strain. We evaluated interobserver and intraobserver TTE
      reproducibility for 2D LV global longitudinal (GLS) and circumferential strain
      (GCS) estimates using data from severe aortic stenosis (AS) subjects with
      preserved LV ejection fraction (EF). METHODS: Twenty severe AS subjects (11 male;
      mean age, 75+/-7years; LV EF >50%) underwent TTE (Vivid E9, GE Healthcare).
      Quantitative strain measurements of whole, endocardial, and epicardial layers
      were performed. GLS was defined as all 17 averaged LV segments, according to the
      American Heart Association classification. GCS was measured at the levels of the
      mitral valve, papillary muscle, and apex. RESULTS: Interobserver correlation
      coefficients in whole, endocardial, and epicardial layers for GLS estimates were
      0.81, 0.83, and 0.80, respectively, whereas those for GCS estimates were 0.38,
      0.56, and 0.19, respectively, for the mitral valve, 0.44, 0.54, and 0.36,
      respectively, for the papillary muscle, and 0.55, 0.29, and 0.59, respectively,
      for the apex. Intraobserver correlation coefficients in whole, endocardial, and
      epicardial layers for GLS estimates were 0.97, 0.97, and 0.94, respectively,
      whereas those for GCS estimates were 0.86, 0.81, and 0.50 , respectively, for the
      mitral valve, 0.56, 0.72, and 0.28, respectively, for the papillary muscle, and
      0.70, 0.69, and 0.62, respectively, for the apex. CONCLUSION: In severe AS
      subjects with preserved LVEF, inter- and intra-observer TTE reproducibility in
      whole, endocardial, and epicardial layers were more consistent for 2D LV GLS than
      for 2D LVGCS.

PMID- 27886614
TI  - Concerns about the ESC heart failure guidelines.

PMID- 27886612
TI  - Decreased Norton's functional score is an independent long-term prognostic marker
      in hospital survivors of acute myocardial infarction. Soroka Acute Myocardial
      Infarction II (SAMI-II) project.
AB  - BACKGROUND: Patient function is a risk factor of mortality following acute
      myocardial infarction (AMI). Norton scale (NS) was originally developed to
      estimate the risk for pressure ulcers. It contains 5 domains: mental condition,
      physical condition, mobility, activity in daily living and incontinence.
      OBJECTIVE: To evaluate NS as long-term prognostic marker following AMI. METHODS:
      A retrospective study based on computerized medical records of AMI patient
      hospitalized in a tertiary medical center in 2004-2012. NS scores and patients'
      characteristics were collected from computerized databases. The primary outcome
      was all-cause long-term (up-to 10-years) mortality. RESULTS: Overall 6964
      patients were included; mean age 67.3+/-14.1years, 68.1% males. Mean NS score was
      17.8+/-3; of which 21.1% had low-NS (<=16). Patients with low-NS had increased
      prevalence of hypertension, diabetes and renal disease, 3-vessel coronary artery
      disease, more often Non ST-Elevation Myocardial Infarction (NSTEMI) and in
      hospital complications. Throughout the follow-up period cumulative mortality rate
      in patients with low- and high-NS groups were 97.3% and 43% respectively (AdjHR
      1.66; 95% CI: 1.521-1.826; p<0.001). Furthermore, a reduction in one point in the
      NS score inversely associated with increased risk for mortality (AdjHR 1.10; 95%
      CI: 1.12-1.22; p<0.001). CONCLUSIONS: NS is an independent long-term prognostic
      marker for all-cause mortality in hospital survivors with a gradual "dose
      response" effect. This data emphasizes the importance prognostic implication of
      the general functional status on the prognosis of AMI patients.

PMID- 27886613
TI  - Computed tomography is important in appropriately diagnosing patients with third
      degree atrioventricular block and second-degree atrioventricular block but not
      Wenckebach type.
AB  - PURPOSE: To evaluate CT utility for detection of cardiac or lung abnormalities in
      the diagnosis of organic cardiac disease in subjects with second- or third-degree
      atrioventricular block (AVB) excepting Wenckebach type. MATERIALS AND METHODS: A
      total of 50 consecutive patients (25 male; 64+/-15years) with de novo third- or
      second-degree AVB underwent both TTE and a combination of cardiac and chest 320
      slice CT (Aquilion one, Toshiba Medical) and were retrospectively analyzed. The
      presence of focal left ventricular (LV) wall thinning and thickening was
      evaluated on both TTE and cardiac CT. We evaluated the presence of significant
      coronary artery stenosis, focal late enhancement (LE) in LV myocardium,
      significant-sized (>10mm) lymph nodes in hialus or mediastinum and/or typical
      lung nodules for sarcoidosis on CT. RESULTS: Abnormalities for 26%, 30%, and 36%
      of patients were demonstrated on TTE, cardiac CT, and a combination of cardiac
      and chest CT, respectively. 12% and 18% patients who did not exhibit cardiac
      abnormalities on TTE, revealed abnormalities on cardiac CT, or a combination of
      cardiac and chest CT, respectively. 36% patients had organic cardiac diseases.
      Sensitivities for detection of organic cardiac disease were significantly greater
      when cardiac and chest CT were combined than TTE alone (P<0.01). CONCLUSIONS:
      Approximately one third of patients with third- or second-degree AVB had organic
      cardiac diseases. For detection of cardiac and chest abnormality and correct
      diagnosis of organic cardiac disease in patients with third- or second-degree
      AVB, TTE is not sufficient on its own. CT or a combination of TTE and CT are
      required.

PMID- 27886615
TI  - HFpEF and HFrEF exhibit different phenotypes as assessed by leptin and
      adiponectin.
AB  - BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) exhibits a
      "reverse metabolic profile". Whether this profile exists in HF with preserved
      ejection fraction (HFpEF) is unknown. We tested the hypothesis that HFpEF and
      HFrEF are similar regarding concentrations of and prognostic impact of leptin and
      adiponectin. METHODS: In patients with HFpEF(n=79), HFrEF(n=84), and
      controls(n=71), we analyzed serum leptin and adiponectin concentrations, their
      correlations, and associations with outcome. RESULTS: Leptin levels in HFpEF and
      HFrEF were increased (p<0.05) compared to controls; with the highest levels in
      HFpEF, median (IQR), 23.1 (10.2-51.0), vs. HFrEF 15.0 (6.2-33.2), and vs.
      controls 10.8 (5.4-18.9) ng/mL.There was no difference between HFpEF and HFrEF
      p=0.125 (adjusted for gender, BMI and age). Leptin was inversely associated with
      NT-proBNP (r=-0.364 p=0.001) and associated with better outcome in HFrEF (HR per
      ln increase of leptin 0.76, 95% CI 0.58-0.99, p=0.044) but not in HFpEF. Crude
      levels of adiponectin were similar in HFpEF: 11.8 (7.9-20.1), HFrEF: 13.7 (7.0
      21.1), and controls: 10.5 (7.4-15.1) MUg/L. In men, adjusted similarly as leptin,
      there was no difference between HFpEF and HFrEF, p=0.310 but, compared to
      controls, higher levels in HFpEF (p=0.044) and HFrEF (p=0.001). Adiponectin
      correlated positively with NT-proBNP; r=0.396 p<0.001 and higher levels were
      associated with adverse outcome only in HFrEF (HR per ln increase 2.88 (95% CI
      1.02-8.14, p=0.045). CONCLUSION: HFpEF and HFrEF share elevated levels of leptin
      and adiponectin. However, the concept of reverse metabolic profile could not be
      confirmed in HFpEF, suggesting that HFpEF might have a conventional metabolic
      profile, rather than a distinct HF syndrome.

PMID- 27886617
TI  - Transcatheter versus surgical aortic valve replacement in low to intermediate
      risk patients: A meta-analysis of randomized and observational studies.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become the
      treatment of choice for patients with aortic stenosis and the preferred
      alternative for high surgical risk patients. However, TAVR's suitability for
      patients at low to intermediate risk still remains controversial. METHODS:
      PubMed, MEDLINE and Clinical trials were systematically searched for randomized
      control trials and observational cohort studies which reported the clinical
      outcomes of TAVR versus surgical aortic valve replacement (SAVR) in patients at
      low to intermediate surgical risk. Clinical endpoints including death, acute
      kidney injury, myocardial infarction, and major adverse cardiac and
      cerebrovascular events (MACCE) were assessed. RESULTS: From 2000 to 2016, 7
      clinical studies comprising 6214 patients were identified. In each time point (in
      hospital or 30days, 1year), TAVR was associated with similar incidence of death
      from any cause, cardiovascular death and MACCE. TAVR reduced short-term incidence
      of myocardial infarction and cerebrovascular events. However, TAVR was associated
      with a higher rate of major vascular complications and permanent pacemaker
      implantation. CONCLUSIONS: Comparing with SAVR in patients at low to intermediate
      surgical risk, TAVR has similar rates of mortality and MACCE, lower incidence of
      acute kidney injury and new-onset atrial fibrillation, but an increase in major
      vascular complications and permanent pacemaker implantation.

PMID- 27886616
TI  - Serial FDG-PET scans help to identify steroid resistance in cardiac sarcoidosis.
AB  - BACKGROUND: Cardiac sarcoidosis (CS) is increasingly being recognized.
      Immunosuppression with corticosteroids is the mainstay of therapy. But the
      optimal dose of steroids and how to assess response to therapy is not known.
      Prognosis is poor if these patients are untreated or undertreated. Fluorine-18
      flurodeoxyglucose positron emission computed tomography (18FDG-PET CT) is a
      sensitive tool in diagnosing CS. It correlates closely with the level of
      granulomatous inflammation and can be used to monitor response to therapy.
      METHODS: We identified 15 patients (6 women; mean age, 42.9+/-12.5years) based on
      histopathological diagnosis. All had a baseline and follow-up fasting 18FDG-PET
      CT scans before and after steroid therapy. Non-responders were defined as those
      in whom ventricular arrhythmias, symptoms of HF and left ventricular systolic
      function and/or ventricular arrhythmias did not improve or worsened despite
      steroid therapy. FDG uptake of involved myocardium and lymph nodes (LN) was
      compared in clinical responders and non-responders on follow-up. RESULTS: Of the
      15 patients, 4 were clinical non-responders to steroid therapy. Follow-up 18FDG
      PET CT was performed at 125.8+/-54.2days after the initiation of steroid therapy.
      Myocardial maximum standardized uptake of FDG (SUVmax) value decreased
      significantly in responders (p=0.004) while there was an increase in non
      responders (p<0.05) on follow-up. Number of left ventricle (LV) segments with FDG
      uptake significantly decreased in responders (p=0.007), and on increasing trend
      in non-responders (p=0.465). Heterogeneous FDG uptake on baseline PET scan,
      increase in intensity as well as area of myocardial inflammation on follow-up PET
      scan was associated with poor clinical outcome despite steroid therapy.
      CONCLUSIONS: Serial 18FDG-PET CT scans can be used to monitor steroid therapy in
      active CS. Increase in PET uptake after steroid therapy correlates with poor
      clinical outcome. Repeat PET scan may help to predict steroid-resistant CS and
      the need for up-titration of immunosuppressive therapy among poor responders to
      initial therapy.

PMID- 27886618
TI  - Massive parallel sequencing questions the pathogenic role of missense variants in
      dilated cardiomyopathy.
AB  - BACKGROUND: Germline genetic variants are an important cause of dilated
      cardiomyopathy (DCM). However, recent sequencing studies have revealed rare
      variants in DCM-associated genes also in individuals without known heart disease.
      In this study, we investigate variant prevalence and genotype-phenotype
      correlations in Swedish DCM patients, and compare their genetic variants to those
      detected in reference cohorts. METHODS AND RESULTS: We sequenced the coding
      regions of 41 DCM-associated genes in 176 unrelated patients with idiopathic DCM
      and found 102 protein-altering variants with an allele frequency of <0.04% in
      reference cohorts; the majority were missense variants not previously described
      in DCM. Fifty-five (31%) patients had one variant, and 24 (14%) patients had two
      or more variants in the analysed genes. Detection of genetic variants in any
      gene, and in LMNA, MYH7 or TTN alone, was associated with early onset disease and
      reduced transplant-free survival. As expected, nonsense and frameshift variants
      were more common in DCM patients than in healthy individuals of the reference
      cohort 1000 Genomes Europeans. Surprisingly however, the prevalence, conservation
      and pathogenicity scores, and localization of missense variants were similar in
      DCM patients and healthy reference individuals. CONCLUSION: To our knowledge,
      this is the first study to identify correlations between genotype and prognosis
      when sequencing a large number of genes in unselected DCM patients. The similar
      distribution of missense variants in DCM patients and healthy reference
      individuals questions the pathogenic role of many variants, and suggests that
      results from genetic testing of DCM patients should be interpreted with caution.

PMID- 27886619
TI  - Open-label therapy with alirocumab in patients with heterozygous familial
      hypercholesterolemia: Results from three years of treatment.
AB  - BACKGROUND: PCSK9 inhibition with alirocumab significantly reduced LDL-C levels
      in trials of up to 78weeks' duration in patients with heterozygous familial
      hypercholesterolemia (HeFH). We report results from 3years of an ongoing open
      label treatment extension (NCT01576484) to a 12-week double-blind trial in HeFH
      patients (NCT01266876). METHODS: Patients who completed the parent study and were
      receiving stable daily statin+/-ezetimibe could enter the open-label extension,
      where they received alirocumab 150mg every 2 weeks (Q2W) subcutaneously (n=58).
      The primary endpoint was safety (treatment-emergent adverse events, TEAEs).
      Efficacy endpoints included the percentage change in LDL-C from baseline at Week
      24. Safety and efficacy data were available up to Weeks 156 and 148,
      respectively. RESULTS: Mean baseline LDL-C was 150.7mg/dL (3.9mmol/L), despite
      all patients being on a statin (76% on high-intensity statin; 72% also receiving
      ezetimibe). Over 156weeks, 54 (93.1%) patients experienced a TEAE, 12 (20.7%)
      experienced a serious TEAE, and two (3.4%) discontinued due to a TEAE. Injection
      site reactions occurred in 21 (36.2%) patients. Mean (SD) reduction in LDL-C from
      baseline to Week 24 was 65.4 (21.1)%, with reductions maintained through 148weeks
      (Week 148 reduction: 56.0 [23.8]%). Mean apolipoprotein B reduction was 50.9% and
      median lipoprotein (a) reduction was 22.5% at Week 24 (46.1% and 25.6% at Week
      148, respectively). CONCLUSIONS: Open-label treatment for 3years with alirocumab
      150mg Q2W, administered with background statin+/-ezetimibe, was generally well
      tolerated and had a safety profile comparable with that seen in the overall
      alirocumab clinical trial program. Alirocumab provided significant, sustained LDL
      C reductions.

PMID- 27886621
TI  - Evaluation of two nucleophilic syntheses routes for the automated synthesis of 6
      [18F]fluoro-l-DOPA.
AB  - Two different strategies for the nucleophilic radiosynthesis of [18F]F-DOPA were
      evaluated regarding their applicability for an automated routine production on an
      Ecker&Ziegler Modular-Lab Standard module. Initially, we evaluated a promising 5
      step synthesis based on a chiral, cinchonidine-derived phase-transfer catalyst
      (cPTC) being described to give the product in high radiochemical yields (RCY),
      high specific activities (AS) and high enantiomeric excesses (ee). However, the
      radiosynthesis of [18F]F-DOPA based on this strategy showed to be highly complex,
      giving the intermediate products as well as the final product in insufficient
      yields for automatization. Furthermore, the automatization proved to be
      problematic due to incomplete radiochemical conversions and the formation of
      precipitates during the enantioselective reaction step. Furthermore, the required
      use of HI at 180 degrees C during the last reaction step led to partial
      decomposition of lines and seals of the module which further counteracts an
      automatization. Further on, we evaluated a 3-step synthesis using the
      commercially available, enantiomerically pure precursor AB1336 for
      automatization. This synthesis approach gave much better results and [18F]F-DOPA
      could be produced fully automated within 114min in RCYs of 20+/-1%, ee of >96%, a
      radiochemical purity (RCP) of >98% and specific activities of up to 2.2GBq/MUmol.

PMID- 27886620
TI  - PET measurement of "GABA shift" in the rat brain: A preclinical application of
      bolus plus constant infusion paradigm of [18F]flumazenil.
AB  - INTRODUCTION: We measured the tiagabine-induced enhancement of the GABAA
      receptor's affinity for benzodiazepine ligands ("GABA shift") using
      [18F]flumazenil (FMZ) PET with preclinical application of bolus plus constant
      infusion (B/I). Differences in quantified results of [18F]FMZ binding were
      compared to that of [18F]FMZ PET with single bolus injection (SB). MATERIALS AND
      METHODS: Sprague-Dawley rats underwent [18F]FMZ PET scans with B/I, which
      consisted of baseline and "GABA shift" sessions in a scan, or scans with SB one
      week apart. Tiagabine (10mg/kg) was intravenously injected after the baseline
      session. [18F]FMZ binding potentials (BPND) were calculated using an equilibrium
      ratio method and a modeling method for B/I and SB, respectively. Regional brain
      BPND changes (%) before and after the tiagabine treatment were also calculated.
      RESULTS: In PET studies with B/I (Kbol=20min), [18F]FMZ distribution in the
      various cortical and subcortical regions rapidly reached equilibrium. After the
      tiagabine treatment, [18F]FMZ BPND were substantially increased across the
      regions of interest (the frontal cortex, hippocampus, thalamus, and striatum),
      ranging from 3% to 7% BPND change (B/I) and 6-14% BPND change (SB), respectively.
      In PET studies with SB, a statistically significant increase of [18F]FMZ BPND was
      found only in the striatum, due to the greater inter-individual variance compared
      to those with B/I. CONCLUSIONS: Data demonstrated that an [18F]FMZ PET study with
      B/I (Kbol=20min) is both reliable and sensitive for the assessment of altered
      GABAA receptor function induced by tiagabine treatment in the rat brain. These
      results may help to improve the efficiency of the development of new GABA
      targeting drugs in the preclinical stage using [18F]FMZ PET.

PMID- 27886624
TI  - Complementary knowledge sharing: Experiences of nursing students participating in
      an educational exchange program between Madagascar and Norway.
AB  - AIM AND OBJECTIVES: To describe how Malagasy and Norwegian nursing students
      experience an educational exchange program in Madagascar. BACKGROUND: Previous
      studies show that nursing students participating in an educational exchange
      program enhanced their cultural knowledge and experienced personal growth.
      However, few studies have described two-way exchange programs, including
      experiences from both the hosts' and the guest students' perspectives. DESIGN:
      This study applies a descriptive qualitative design. METHODS: Data were collected
      in 2015 by means of five semi-structured interviews with Malagasy students and
      two focus group interview sessions with Norwegian students. They were analysed
      using qualitative content analysis. The study was conducted in Madagascar.
      FINDINGS: The data analyses revealed one main theme and two sub-themes related to
      the Malagasy and Norwegian nursing students' experiences. Main theme:
      complementary knowledge sharing; sub-themes: (1) learning from each other and (2)
      challenges of working together. CONCLUSION: The findings indicate that both the
      Malagasy and Norwegian nursing students experienced the exchange program as
      valuable and essential in exchanging knowledge. They also highlighted challenges,
      linked mainly to language barriers and the lack of available resources.

PMID- 27886623
TI  - Liver BCATm transgenic mouse model reveals the important role of the liver in
      maintaining BCAA homeostasis.
AB  - Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass
      first-pass liver degradation due to a lack of hepatocyte expression of the
      mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan
      shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To
      explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in
      peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two
      transgenic mouse lines with low and high hepatocyte expression of the BCATm
      transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and
      plasma amino acid concentrations and determine whether the first two BCAA
      enzymatic steps in liver, skeletal muscle, heart and kidney were impacted.
      Expression of the hepatic BCATm transgene lowered the concentrations of hepatic
      BCAAs while enhancing the concentrations of some nonessential amino acids.
      Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely
      unaffected, and no growth rate or body composition differences were observed in
      the transgenic animals as compared to wild-type mice. Feeding the transgenic
      animals a high-fat diet did not reverse the effect of the BCATm transgene on the
      hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma
      BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced
      attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and
      had impaired blood glucose tolerance. These results suggest that complete liver
      BCAA metabolism influences the regulation of glucose utilization during diet
      induced obesity.

PMID- 27886625
TI  - Culturally construed beliefs and perceptions of nursing students and the stigma
      impacting on people living with AIDS: A qualitative study.
AB  - BACKGROUND: Since HIV and AIDS were discovered, studies have demonstrated that
      negative perceptions and reluctance to provide care to affected people persist
      among nursing students throughout the world. This leads to poor quality care.
      OBJECTIVES: To report on a study that explored socio-cultural influences on the
      perceptions of international nursing students toward caring for people living
      with HIV/AIDS. METHODS: A qualitative descriptive research design, guided by
      stigma theory, was utilised. Participants were 21 international and Australian
      undergraduate nursing students enrolled in a Bachelor of Nursing program at an
      Australian university. Data were collected via semi-structured interviews in 2009
      and 2011; manual thematic analysis was performed on interview data. FINDINGS:
      Three major themes emerged: blame; othering; values. Perceptions were influenced
      by complex, interrelated factors and underscored by culturally construed blame
      and othering. People living with HIV/AIDS were perceived as alien and assumed as
      homosexuals, drug users, or promiscuous. They were labelled 'bad people'. Many
      participants were compassionate but others struggled with differences between
      their personal values and professional values expected of a Registered Nurse.
      There was considerable variation in the degree to which participants were willing
      to embrace different perspectives and values. CONCLUSION: Nursing curricula is
      vital to patient health and wellbeing and requires increased focus on the impact
      of HIV/AIDS. It is important for educators to recognise that simply providing
      information to students does not necessarily change their existing stigmatising
      perceptions. By addressing the effect of being stigmatised and marginalised by
      society nursing care to all patients will be enhanced. Students must also reflect
      on their perceptions and values so as to embrace diversity.

PMID- 27886622
TI  - Linoleic acid causes greater weight gain than saturated fat without hypothalamic
      inflammation in the male mouse.
AB  - A significant change in the Western diet, concurrent with the obesity epidemic,
      was a substitution of saturated fatty acids with polyunsaturated, specifically
      linoleic acid (LA). Despite increasing investigation on type as well as amount of
      fat, it is unclear which fatty acids are most obesogenic. The objective of this
      study was to determine the obesogenic potency of LA vs. saturated fatty acids and
      the involvement of hypothalamic inflammation. Forty-eight mice were divided into
      four groups: low-fat or three high-fat diets (HFDs, 45% kcals from fat) with LA
      comprising 1%, 15% and 22.5% of kilocalories, the balance being saturated fatty
      acids. Over 12 weeks, bodyweight, body composition, food intake, calorimetry, and
      glycemia assays were performed. Arcuate nucleus and blood were collected for mRNA
      and protein analysis. All HFD-fed mice were heavier and less glucose tolerant
      than control. The diet with 22.5% LA caused greater bodyweight gain, decreased
      activity, and insulin resistance compared to control and 1% LA. All HFDs elevated
      leptin and decreased ghrelin in plasma. Neuropeptides gene expression was higher
      in 22.5% HFD. The inflammatory gene Ikk was suppressed in 1% and 22.5% LA. No
      consistent pattern of inflammatory gene expression was observed, with suppression
      and augmentation of genes by one or all of the HFDs relative to control. These
      data indicate that, in male mice, LA induces obesity and insulin resistance and
      reduces activity more than saturated fat, supporting the hypothesis that
      increased LA intake may be a contributor to the obesity epidemic.

PMID- 27886626
TI  - Describing clinical faculty experiences with patient safety and quality care in
      acute care settings: A mixed methods study.
AB  - BACKGROUND: A major safety initiative in acute care settings across the United
      States has been to transform hospitals into High Reliability Organizations. The
      initiative requires developing cognitive awareness, best practices, and
      infrastructure so that all healthcare providers including clinical faculty are
      accountable to deliver quality and safe care. OBJECTIVE: To describe the
      experience of baccalaureate clinical nursing faculty concerning safety and near
      miss events, in acute care hospital settings. METHODS: A mixed method approach
      was used to conduct the pilot study. Nurse faculty (n=18) completed study surveys
      from the Agency for Healthcare Research and Quality (AHRQ) to track patient
      safety concerns: Incidents; Near misses; or Unsafe conditions, during one
      academic semester, within 9 different acute care hospitals. Additionally, seven
      nurse faculty participated in end of the semester focus groups to discuss the
      semester long experience. RESULTS: Clinical faculty identified a total of 24
      patient occurrences: 15 Incidents, 1 Near miss event, and 8 Unsafe conditions.
      Focus group participants (n=7) described benefits and challenges experienced by
      nursing clinical faculty and students in relation to the culture of safety in
      acute care hospital settings. Six themes resulted from the content analysis.
      CONCLUSIONS: Utilizing nursing clinical faculty and students may add significant
      value to promoting patient safety and the delivery of quality care, within acute
      care hospital settings.

PMID- 27886627
TI  - Facilitating the development of higher-order thinking skills (HOTS) of novice
      nursing postgraduates in Africa.
AB  - BACKGROUND: International research in nursing education has shown to be deficient
      regarding both the quality of research produced and the building of disciplinary
      capacity. The CHENMA (Collaboration for Higher Education of Nurses and Midwives
      in Africa) project aimed to strengthen nursing and midwifery expertise in Africa.
      Sixteen French-speaking students of the Democratic Republic of the Congo (DRC)
      enrolled for a master's degree in nursing midwifery at a South African university
      in 2008. Ten of the initial 16 students graduated with a master's degree in 2012.
      One student withdrew and five students completed a postgraduate diploma in
      midwifery. OBJECTIVES: The objective of this paper is to explore the quality of
      the output of those master's degree students, namely their dissertation (with
      specific reference to the demonstration of HOTS). METHODS: An exploratory,
      evaluative, single, descriptive case study was utilised. Realist, purposeful
      sampling was used. Six of the 10 completed final dissertations were evaluated as
      well as three reflective reports from the supervisor, translator and critical
      reader. RESULTS: The findings indicated that most dissertations fell below the
      expected standard, with a paucity of higher-order thinking and application
      skills. Language, and possibly cultural dynamics, seemed to be the largest
      barrier to learning and communication. The dissertations lacked conceptual
      skills, scientific writing skills, logical order of thought and congruency.
      Analysis of the dissertations revealed a limited ability of novice scholars to
      explore the nature of information and to interpret and manipulate the data in a
      novel way.

PMID- 27886628
TI  - EEG utilization in Canadian intensive care units: A multicentre prospective
      observational study.
AB  - PURPOSE: We have previously shown that electroencephalography (EEG) may be an
      underutilized monitoring modality in a single general medical-surgical ICU, that
      does not have a specific neurocritical care consultation service or neurocritical
      care unit. The present study was designed to describe the pattern of EEG
      utilization across 3 academic ICUs in Ontario, Canada that use different models
      of neurocritical care. METHOD: In this prospective multicentre observational
      study, ICU patients were screened weekly for 6 non-consecutive weeks to determine
      if they met the ESICM's recommendations or suggestions for EEG monitoring. If
      EEGs were performed, the results were recorded. Three models of neurocritical
      care provision were examined in 3 academic tertiary ICUs. Site 1 is an
      intensivist-led, medical-surgical ICU with no specific neurocritical care
      consultation service. The second site is also an intensivist led medical-surgical
      ICU, but with a formal neurocritical care consultation service. The third site is
      a virtual neurological and neurotrauma ICU within a medical-surgical ICU, staffed
      by rotating neurointensivists and general intensivists. RESULTS: Of the 375
      patients who were screened, 127 patients (34%) met at least one ESICM indication
      for EEG monitoring. Among the 127 patients, 46 patients (37%) had an EEG
      performed. Site 1 had the highest proportion of EEGs performed. The most common
      indication for EEG monitoring was for patients with unexplained altered level of
      consciousness, in the absence of primary brain injury. For the EEGs performed per
      ESICM indication, the majority of epileptiform abnormalities were found in
      patients admitted with status epilepticus. CONCLUSIONS: EEG may be underutilized
      in Canadian ICUs. The impact on patient management and outcomes are unknown.

PMID- 27886629
TI  - Transient Epileptic Amnesia over twenty years: Long-term follow-up of a case
      series with three detailed reports.
AB  - PURPOSE: Transient Epileptic Amnesia (TEA) is a form of adult onset temporal lobe
      epilepsy characterised by ictal amnesia. The amnesic seizures are often
      accompanied by interical memory disturbance, involving autobiographical amnesia
      and accelerated long-term forgetting. Short-term follow-up studies suggest a
      relatively stable cognitive profile once treated, but recent case reports raise
      concerns regarding the risk of developing Alzheimer's disease (AD). The current
      study reports clinical and cognitive outcome in TEA patients over a 20-year
      period. METHODS: A cohort of ten TEA patients first reported in 1998 were
      followed up at two time intervals, each 10 years apart. Information regarding
      clinical outcomes and subjective reports of memory functioning was gained via GP
      records and clinical interview. Objective memory function was determined at each
      time point via a comprehensive neuropsychological assessment, where possible.
      RESULTS: Information was obtained for nine of the original 10 participants. Over
      the 20-year period, 4 participants died, with no indication of dementia prior to
      death. One participant was diagnosed with Vascular Dementia. Seizures were
      generally well controlled. Subjective reports of memory varied, including no
      concerns, stable memory difficulties, and worsening memory. Neuropsychological
      assessment at 10 years showed stable performances across most measures. At the 20
      year follow up, there was no evidence of a general cognitive decline.
      Participants showed stability on some measures, with reductions on others.
      Performance was not consistent with AD. CONCLUSIONS: No elevated risk of dementia
      was evident from this TEA series. Although memory difficulties persist over time,
      the prognosis of TEA appears generally benign.

PMID- 27886630
TI  - The role of antiepileptic drugs in sudden unexpected death in epilepsy.
AB  - Sudden unexpected death in epilepsy (SUDEP) primarily affects young adults and is
      the leading cause of death related directly to seizures. High frequency of
      generalized tonic-clonic seizures is the most important risk factor, and
      effective seizure protection is probably the most important measure to prevent
      these tragic deaths. For several years a potential role of antiepileptic drugs
      (AEDs) has been discussed, but at present there is wide agreement that choice of
      AED therapy does not influence the risk. However, although it is well known that
      the efficacy and safety profiles of AEDs may differ significantly when used in
      the treatment of genetic epilepsy compared to symptomatic or cryptogenic
      epilepsy, this has generally been overlooked in epidemiologic studies of possible
      relationships between AEDs and SUDEP. Consequently important information about
      drug safety may have been lost. This review challenges the current view that no
      AED can increase the risk of SUDEP.

PMID- 27886632
TI  - Exploring the potential of iTRAQ proteomics for tracking the transformation of
      extracellular proteins from enzyme-disintegrated waste activated sludge.
AB  - To characterize the transformation of extracellular proteins extracted from raw
      and enzyme-disintegrated waste activated sludge (WAS), extracts of extracellular
      polymeric substances (EPS) were subject to isobaric tags for relative and
      absolute quantitation (iTRAQ) proteomics analysis. 209 proteins were identified
      and categorized into three Gene Ontology classifications: "cellular components",
      "molecular function", and "biological processes". Most identified proteins
      originated from intracellular components, organelles, or cytoplasm, suggesting
      that cell decline and lysis represent the main sources of extracellular proteins
      in WAS. The major protein functions comprised "transporter binding activity",
      "macromolecule metabolic process", and "biosynthesis enzyme catalytic activity".
      In total, 15 proteins categorized as "membrane part" and "biological adhesion"
      and 10 as "organelle" were down- or up-regulated, respectively, implying that the
      enzyme-disintegration mainly induced WAS floc-structure disintegration via
      membrane structure and corresponding biological adhesion disruption. The
      proteomics study will provide valuable clues to better understand EPS changes
      associated with enzymatic treatment at molecular levels.

PMID- 27886631
TI  - Metagenomics analysis reveals a new metallothionein family: Sequence and metal
      binding features of new environmental cysteine-rich proteins.
AB  - Metallothioneins are cysteine-rich proteins, which function as (i) metal carriers
      in basal cell metabolism and (ii) protective metal chelators in conditions of
      metal excess. Metallothioneins have been characterized from different eukaryotic
      model and cultivable species. Presently, they are categorized in 15 families but
      evolutionary relationships between these metallothionein families remain
      unresolved. Several cysteine-rich protein encoding genes that conferred Cd
      tolerance in Cd-sensitive yeast mutants have previously been isolated from soil
      eukaryotic metatranscriptomes. They were called CRPs for "cysteine-rich
      proteins". These proteins, of unknown taxonomic origins, share conserved cysteine
      motifs and could be considered as metallothioneins. In the present work, we
      analyzed these CRPs with respect to their amino acid sequence features and their
      metal-binding abilities towards Cd, Zn and Cu metal ions. Sequence analysis
      revealed that they share common features with different known metallothionein
      families, but also exhibit unique specific features. Noticeably, CRPs display two
      separate cysteine-rich domains which, when expressed separately in yeast, confer
      Cd-tolerance. The N-terminal domain contains some conserved atypical Cys motifs,
      such as one CCC and two CXCC ones. Five CRPs were expressed and purified as
      recombinant proteins and their metal-binding characteristics were studied. All
      these CRPs chelated Cd(II), Zn(II) and Cu(I), although displaying a better
      capacity for Zn(II) coordination. All CRPs are able to confer Cd-tolerance, and
      four of them confer Zn-tolerance in the Zn-sensitive zrc1Delta yeast mutant. We
      designated these CRPs as environmental metallothioneins belonging to a new
      formerly undescribed metallothionein family.

PMID- 27886633
TI  - A novel method to harvest Chlorella sp. via low cost bioflocculant: Influence of
      temperature with kinetic and thermodynamic functions.
AB  - In this study, harvesting efficiency (HE) of bioflocculant (egg shell) was
      observed with variation in flocculent concentrations (0-100mgL-1), temperature
      (30 degrees C, 35 degrees C 40 degrees C, 45 degrees C and 50 degrees C) and
      variable contact time (0-50min). It was found maximum (~95.6%) with 100mgL-1
      bioflocculant concentration whereas influence of temperature was also observed
      with optimized concentration of bioflocculant (100mgL-1) at 40 degrees C (~98.1%)
      and 50 degrees C (~99.3%), in 30min of contact time. Significant changes in algal
      cell structures were also analyzed after exposure to various temperatures with
      microscopy, SEM (Scanning electron microscopy) and EDS (Energy dispersive X-ray
      spectroscopy) images with and without bioflocculant. The experimental data was
      found to be a good fit with pseudo-second order kinetic model. The thermodynamic
      functions such as DeltaG (Gibbs free energy), DeltaH (enthalpy), DeltaS (entropy)
      were also determined. The negative value of DeltaG and positive value of DeltaH
      and DeltaS shows the spontaneous and endothermic nature of flocculation process.

PMID- 27886634
TI  - Influence of lead in the sorption of arsenate by municipal solid waste composts:
      metal(loid) retention, desorption and phytotoxicity.
AB  - The ability of two municipal solid waste composts (MSW-C) to sorb As(V) in the
      presence of Pb(II) and in acidic conditions was investigated. Sorption isotherms
      and kinetics showed that both MSW-C were able to sorb As(V) in a similar way
      (~0.24mmolg-1 MSW-C), but only when Pb(II) was present (0.45mmolL-1). The
      concomitant sorption of Pb(II) by both MSW-C (~0.40mmolg-1) suggested that the
      metal cation was likely acting as bridging element between the negatively charged
      functional groups of composts and As(V). SEM-EDX analysis of the MSW
      C+Pb(II)+As(V) systems supported the association between Pb(II) and As(V), while
      sequential extraction procedures and organic acids treatment showed that As(V)
      was strongly retained by MSW-C+Pb(II) and suggested the presence of different
      interaction types between As(V) and Pb(II). Plant growth experiments highlighted
      the key role of Pb(II) in the reduction of As(V)-phytotoxicity for triticale
      plants (*Triticosecale Wittm.) in the presence of MSW-C.

PMID- 27886635
TI  - Multiplex PCR reveals that viruses are more frequent than bacteria in children
      with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is a degenerative disease characterized by
      progressive epithelial secretory gland dysfunction associated with repeated
      respiratory infections. Bacterial infections are very frequent in children with
      cystic fibrosis, but because rapid METHODS: for screening for the wide variety of
      potentially involved viruses were unavailable until recently, the frequency of
      viral presence is unknown. Multiplex PCR enables screening for many viruses
      involved in respiratory infections. OBJECTIVES: This study aimed to evaluate the
      frequency of viruses and bacteria in respiratory specimens from children with
      cystic fibrosis and to clarify the incidence and characteristics (seasonality and
      age of patients) of different viruses detected in children with cystic fibrosis.
      STUDY DESIGN: In this 2-year prospective study, we obtained paired nasopharyngeal
      swab and sputum specimens from children with cystic fibrosis during clinical
      respiratory examinations separated by at least 14days. We analyzed viruses in
      nasopharyngeal-swab specimens with multiplex PCR and bacteria in sputum with
      standard methods. RESULTS: We analyzed 368 paired specimens from 33 children. We
      detected viruses in 154 (41.8%) and bacteria in 132 (35.9%). Bacteria were
      commoner in spring and summer; viruses were commoner in autumn and winter. In
      every season, Staphylococcus aureus was the commonest bacteria and rhinovirus was
      the commonest virus. Nearly all infections with Haemophilus influenzae occurred
      in autumn and winter. Viruses were more prevalent in children <5 years old, and
      bacteria were more prevalent in children >=12 years old. CONCLUSIONS: Multiplex
      PCR screening for respiratory viruses is feasible in children with cystic
      fibrosis; the clinical implications of screening warrant further study.

PMID- 27886636
TI  - The impact of social support, unit cohesion, and trait resilience on PTSD in
      treatment-seeking military personnel with PTSD: The role of posttraumatic
      cognitions.
AB  - BACKGROUND: The personal resources of social support, unit cohesion, and trait
      resilience have been found to be associated with posttraumatic stress disorder
      (PTSD) severity among military personnel. However, the underlying mechanisms of
      these relationships are unclear. We hypothesized that negative posttraumatic
      cognitions, which are associated with PTSD, mediate the relationships between
      these personal resources and PTSD. METHODS: The relationship between PTSD symptom
      severity and a latent factor comprised of social support, unit cohesion, and
      trait resilience was evaluated using cross-sectional data from 366 treatment
      seeking active duty military personnel with PTSD following deployments to or near
      Iraq or Afghanistan. Structural equation modeling (SEM) was used to test whether
      posttraumatic cognitions mediated this relationship. RESULTS: The SEM model
      indicated that (1) a robust latent variable named personal resources (indicated
      by social support, unit cohesion, and trait resilience) was negatively associated
      with PTSD severity; (2) personal resources were negatively associated with
      negative posttraumatic cognitions; (3) negative posttraumatic cognitions fully
      mediated the association between personal resources and PTSD severity. The final
      SEM mediation model showed a highly satisfactory fit [chi2 (22) = 16.344, p =
      0.798; chi2/df = 0.743; CFI = 1; RMSEA = 0.000]. CONCLUSIONS: These findings
      suggest that among active duty military personnel seeking treatment for PTSD,
      personal resources (social support, unit cohesion, and trait resilience) may
      mitigate PTSD severity by reducing negative posttraumatic cognitions.

PMID- 27886637
TI  - Handling clinical comorbidity in randomized clinical trials in psychiatry.
AB  - The purpose of this paper is to a) outline the importance of including patients
      with clinical comorbidities in Randomized Clinical Trials (RCTs) of psychiatric
      treatments; and b) to propose a specific approach for best handling, analyzing
      and interpreting the data on clinical comorbidities in terms of their impact on
      treatment outcomes. To do this we first define and describe clinical comorbidity
      and differentiate it from other forms of comorbidity. We then describe the
      methodological and analytical problems associated with excluding patients with
      clinically comorbid conditions from RCTs, including the impact on the outcomes of
      RCTs in psychiatry and the impact on evidence-based clinical decision-making. We
      then address the challenges inherent to including patients with clinical
      comorbidities in RCTs. Finally, we propose a methodological and analytic approach
      to deal with these issues in RCTs which aims to significantly improve the
      information yielded from RCTs in psychiatry, and thus improve clinical decision
      making.

PMID- 27886640
TI  - Perceived importance and responsibility for market-driven pig welfare: Literature
      review.
AB  - This review explores barriers and opportunities for market-driven pig welfare in
      Europe. It finds, first, that consumers generally rank animal welfare as
      important, but they also rank it low relative to other societal problems. Second,
      consumers have a wide range of concerns about pig welfare, but they focus
      especially on naturalness. Third, pig welfare is seen as an important indicator
      of meat quality. Fourth, consumers tend to think that responsibility for pig
      welfare lies with several actors: farmers, governments and themselves. The paper
      concludes that there is an opportunity for the market-driven strategy to sell a
      narrative about naturalness supplemented with other attractive qualities (such as
      eating quality). It also emphasizes that pig welfare needs to be on the
      political/societal agenda permanently if it is to be viewed as an important issue
      by consumers and if consumers are to assume some sort of responsibility for it.

PMID- 27886639
TI  - Hyaluronan-Derived Swelling of Solid Tumors, the Contribution of Collagen and
      Cancer Cells, and Implications for Cancer Therapy.
AB  - Despite the important role that mechanical forces play in tumor growth and
      therapy, the contribution of swelling to tumor mechanopathology remains
      unexplored. Tumors rich in hyaluronan exhibit a highly negative fixed charge
      density. Repulsive forces among these negative charges as well as swelling of
      cancer cells due to regulation of intracellular tonicity can cause tumor swelling
      and development of stress that might compress blood vessels, compromising tumor
      perfusion and drug delivery. Here, we designed an experimental strategy, using
      four orthotopic tumor models, to measure swelling stress and related swelling to
      extracellular matrix components, hyaluronan and collagen, as well as to tumor
      perfusion. Subsequently, interventions were performed to measure tumor swelling
      using matrix-modifying enzymes (hyaluronidase and collagenase) and by repurposing
      pirfenidone, an approved antifibrotic drug. Finally, in vitro experiments on
      cancer cell spheroids were performed to identify their contribution to tissue
      swelling. Swelling stress was measured in the range of 16 to 75 mm Hg, high
      enough to cause vessel collapse. Interestingly, while depletion of hyaluronan
      decreased swelling, collagen depletion had the opposite effect, whereas the
      contribution of cancer cells was negligible. Furthermore, histological analysis
      revealed the same linear correlation between tumor swelling and the ratio of
      hyaluronan to collagen content when data from all tumor models were combined. Our
      data further revealed an inverse relation between tumor perfusion and swelling,
      suggesting that reduction of swelling decompresses tumor vessels. These results
      provide guidelines for emerging therapeutic strategies that target the tumor
      microenvironment to alleviate intratumoral stresses and improve vessel
      functionality and drug delivery.

PMID- 27886641
TI  - Comparison of hot versus cold boning of beef carcasses on bacterial growth and
      the risk of blown pack spoilage.
AB  - Primals were prepared from beef Longissimus thoracis et lumborum (LTL), psoas
      major (PM), quadriceps femoris (QF) and semitendinosus (S) muscles from cold and
      hot boned carcasses, vacuum-packaged and stored for 42 or 100days at 2 degrees C
      and 7 degrees C. Storage temperature, carcass or primal surface temperature, pH
      and aw were monitored. Samples were taken periodically and tested for total
      viable count mesophilic (TVCm), TVC psychrophilic (TVCp), total
      Enterobacteriaceae count (TEC), presumptive Pseudomonas spp., lactic acid
      bacteria (LAB), Clostridium spp. and Brochothrix thermosphacta. A fifth muscle,
      biceps femoris (BF), was used to examine the impact of hot boning on blown pack
      spoilage (BPS). Primal counts increased to 6-7log10cfucm-2 after 6weeks.
      Significantly (P<0.05) higher TEC, Pseudomonas spp. and Br. thermosphacta counts
      were observed on cold versus hot boned primals. In contrast, significantly
      (P<0.05) higher TVC, LAB and Clostridium spp. concentrations were obtained on hot
      boned beef. Moreover, BPS pack distension/bursting occurred considerably sooner
      in hot boned product.

PMID- 27886638
TI  - Preliminary evidence that negative symptom severity relates to multilocus genetic
      profile for dopamine signaling capacity and D2 receptor binding in healthy
      controls and in schizophrenia.
AB  - Deficits in central, subcortical dopamine (DA) signaling may underlie negative
      symptom severity, particularly anhedonia, in healthy individuals and in
      schizophrenia. To investigate these relationships, we assessed negative symptoms
      with the Schedule for the Assessment of Negative Symptoms and the Brief Negative
      Symptom Scale (BNSS) and self-reported anhedonia with the Scales for Physical and
      Social Anhedonia (SPSA), Temporal Experience of Pleasure Scale, and Snaith
      Hamilton Pleasure Scale in 36 healthy controls (HC), 27 siblings (SIB) of
      individuals with schizophrenia, and 66 individuals with schizophrenia or
      schizoaffective disorder (SCZ). A subset of participants (N = 124) were genotyped
      for DA-related polymorphisms in genes for DRD4, DRD2/ANKK1, DAT1, and COMT, which
      were used to construct biologically-informed multi-locus genetic profile (MGP)
      scores reflective of subcortical dopaminergic signaling. DA receptor type 2 (D2R)
      binding was assessed among a second subset of participants (N = 23) using PET
      scans with the D2R-selective, non-displaceable radioligand (N
      [11C]methyl)benperidol. Higher MGP scores, reflecting elevated subcortical
      dopaminergic signaling capacity, were associated with less negative symptom
      severity, as measured by the BNSS, across all participants. In addition, higher
      striatal D2R binding was associated with less physical and social anhedonia, as
      measured by the SPSA, across HC, SIB, and SCZ. The current preliminary findings
      support the hypothesis that subcortical DA function may contribute to negative
      symptom severity and self-reported anhedonia, independent of diagnostic status.

PMID- 27886642
TI  - Obesity and the breast cancer methylome.
AB  - Breast cancer is associated with risk factors such as advancing age and obesity.
      However, the linkages between these risk factors for breast cancer development
      and initiation of the disease are not yet clear. Obesity may drive breast cancer
      development through increases in circulating estrogens in postmenopausal women.
      Mammary cell susceptibility to neoplastic transformation requires both genetic
      and epigenetic alterations, including changes in DNA methylation. Obesity is also
      subject to epigenetic regulation. In this review, the nature of epigenetic
      changes, specifically changes to the methylome, are discussed in the context of
      obesity and breast cancer, and a potential mechanism for the interaction of
      obesity and breast cancer is proposed. This proposed mechanism identifies
      opportunities for intervention (using drugs or biologic therapies) to prevent
      breast cancer development in the obese patient.

PMID- 27886643
TI  - Cardiac safety of adjuvant non-pegylated liposomal doxorubicin combined with
      cyclophosphamide and followed by paclitaxel in older breast cancer patients.
AB  - PURPOSE: To investigate the cardiac safety of adjuvant Non-Pegylated Liposomal
      Doxorubicin (NPL-DOX) combined to Cyclophosphamide (CTX) and followed by weekly
      Paclitaxel, in older patients (>=65 years) with diagnosis of high risk breast
      cancer. The main end point of this prospective study was the detection of early
      episodes of symptomatic congestive heart failure (CHF). METHODS: The cardiac
      function was evaluated by left ventricular ejection fraction (LVEF) measurements
      with repeated echocardiograms, performed 2 weeks before the beginning of
      chemotherapy and every 6 months, until 30 months after the study entry; then
      yearly for at least 5 years. RESULTS: Forty-seven patients were enrolled from two
      Italian Divisions of Medical Oncology. Final results revealed no early episodes
      of symptomatic CHF within the first 12 months from the enrolment. Only two
      cardiac events were observed: an episode of atrial flutter after the first cycle
      of NPL-DOX and CTX, with a quick return to normal rhythm, and a grade 3 (scored
      to NCI-CTCAE, version 3.0) CHF episode, 18 months later chemotherapy start. No
      other relevant toxicities were reported. CONCLUSIONS: This adjuvant combination
      including NPL-DOX in elderly patients, resulted in a low rate of cardiac toxic
      effects. Comparative trials should be encouraged to confirm these findings.

PMID- 27886644
TI  - Oral administration with diosgenin enhances the induction of intestinal T helper
      1-like regulatory T cells in a murine model of food allergy.
AB  - Although the development of T helper (Th)1-like regulatory T (Treg) cells under
      Th1 inflammatory conditions has been reported, the role of Th1-like Treg cells in
      Th2 allergic responses remains mostly unclear. We previously demonstrated that
      diosgenin, the major sapogenin contained in the Chinese yam, attenuated food
      allergy and augmented Th1 and Treg immune responses. In this study, we
      hypothesized that diosgenin may enhance the induction of Th1-like Treg cells in
      the gut of mice with food allergy. Ovalbumin (OVA)-sensitized BALB/c mice were
      gavaged daily with diosgenin and received repeatedly intragastric ovalbumin
      challenges to induce intestinal allergic responses. The induction of Foxp3+ Treg
      cells co-expressing Th1-type transcription factors, cytokines and chemokines in
      the intestine was examined, and the mRNA expression of the chemokines
      corresponding to Th1-like Treg cells was measured. Diosgenin administration
      increased the number of Foxp3+ Treg cells co-expressing Th1 markers, including
      CCR5, CXCR3, IFN-gamma and T-bet in the intestine, and enhanced populations of
      Foxp3+IFN-gamma+ and Foxp3+T-bet+ cells that expressed the regulatory cytokine IL
      10 in the Peyer's patches. Diosgenin also augmented the intestinal expression of
      CXCR3, CCL3, and CXCL10. Concordantly, diosgenin increased the number of
      CXCR3+Foxp3+IL-10 cells in the Peyer's patches. Our data demonstrated the
      enhanced induction of Th1-like Treg cells in allergic mice treated with
      diosgenin, providing evidence to suggest a role for Th1-like Treg cells in
      diosgenin-mediated anti-allergic effects against Th2-type allergy.

PMID- 27886645
TI  - A new 2-(2'-hydroxyphenyl)quinazolin-4(3H)-one derived acylhydrazone for
      fluorescence recognition of Al3.
AB  - A new 2-(2'-hydroxyphenyl)quinazolin-4(3H)-one derived acylhydrazone (QP) was
      designed and synthesized as a fluorescent sensor. In Tris?HCl buffer (10mM,
      pH7.4)/ethanol (1/9, v/v) solution, QP exhibits a highly selective fluorescence
      response to Al3+ over other metal ions with a significant blue-shifted and
      enhanced emission at 473nm. QP interacts with Al3+ reversibly through a 1:2
      binding ratio with a detection limit of 4.79*10-8M. Potential applicability of QP
      for Al3+ detection in tap and lake water samples were also examined by 'proof-of
      concept' experiments.

PMID- 27886647
TI  - High pressure Raman scattering study on Sm2Mo4O15 system.
AB  - High-pressure Raman experiments were performed on Sm2Mo4O15 system up to 7.9GPa.
      We show that this system exhibits an irreversible structural amorphization at
      5.0GPa. In contrast to any other molybdates and tungstates experiencing pressure
      induced amorphization, this structural change in Sm2Mo4O15 has strongly first
      order character. This amorphous phase can be originated from the hindrance of a
      crystalline structural phase transition from the P1- to P2/m structure.
      Additionally, the assignment of Raman modes of the ambient-pressure phase of
      Sm2Mo4O15 was proposed based on lattice dynamics calculations.

PMID- 27886646
TI  - Graphene oxide-based fluorescent sensor for sensitive turn-on detection of
      sinapine.
AB  - Sinapine (SP) has attracted extensive attention in food and medical field because
      it is a crucial component in many plants with unique physiological activities.
      Here, we reported a fluorescent sensor based on the unique properties of graphene
      oxide (GO) for rapid, sensitive detection of SP concentration. In this strategy,
      GO has stronger affinity toward SP and can be also served as a quencher for DNA
      fluorescence probe. The fluorescence can make a recovery by the addition of SP,
      which can competitively desorb probe from the surface of GO, and the SP can thus
      be monitored by recording the fluorescence change. Because of the low background
      assays and high quenching ability offered by GO, the developed method provides a
      great potential for plant-derived molecules research.

PMID- 27886648
TI  - Selective and sensitive fluorimetric determination of carbendazim in apple and
      orange after preconcentration with magnetite-molecularly imprinted polymer.
AB  - In this study, magnetite-molecularly imprinted polymer has been used for the
      first time as selective adsorbent before the fluorimetric determination of
      carbendazim. Adsorption capacity of the magnetite-molecularly imprinted polymer
      was found to be 2.31+/-0.63mgg-1 (n=3). Limit of detection (LOD) and limit of
      quantification (LOQ) of the method were found to be 2.3 and 7.8MUgL-1,
      respectively. Calibration graph was linear in the range of 10-1000MUgL-1.
      Rapidity is an important advantage of the method where re-binding and recovery
      processes of carbendazim can be completed within an hour. The same imprinted
      polymer can be used for the determination of carbendazim without any capacity
      loss repeatedly for at least ten times. Proposed method has been successfully
      applied to determine carbendazim residues in apple and orange, where the
      recoveries of the spiked samples were found to be in the range of 95.7-103%.
      Characterization of the adsorbent and the effects of some potential interferences
      were also evaluated. With the reasonably high capacity and reusability of the
      adsorbent, dynamic calibration range, rapidity, simplicity, cost-effectiveness
      and with suitable LOD and LOQ, the proposed method is an ideal method for the
      determination of carbendazim.

PMID- 27886649
TI  - Spectroscopic investigation, vibrational assignments, HOMO-LUMO, NBO, MEP
      analysis and molecular docking studies of oxoaporphine alkaloid liriodenine.
AB  - A combined experimental and theoretical DFT study of the structural, vibrational
      and electronic properties of liriodenine is presented using B3LYP function with 6
      311G (2d, p) basis set. The theoretical geometry optimization data were compared
      with the X-ray data for a similar structure in the associated literature, showing
      similar values. In addition, natural bond orbitals (NBOs), HOMO-LUMO energy gap,
      mapped molecular Electrostatic Potential (MEP) surface calculation, first and
      second order hyperpolarizabilities were also performed with the same calculation
      level. Theoretical UV spectrum agreed well with the measured experimental data,
      with transitions assigned. The molecular electrostatic potential map shows
      opposite potentials regions that forms hydrogen bonds that stabilize the dimeric
      form, which were confirmed by the close values related to the CO bond stretching
      between the dimeric form and the experimental IR spectra (1654cm-1 for the
      experimental, 1700cm-1 for the dimer form). Calculated HOMO/LUMO gaps shows the
      excitation energy for Liriodenine, justifying its stability and kinetics
      reaction. Molecular docking studies with Candida albicans dihydrofolate reductase
      (DHFR) and Candida albicans secreted aspartic protease (SAP) showed binding free
      energies values of -8.5 and -8.3kcal/mol, suggesting good affinity between the
      liriodenine and the target macromolecules.

PMID- 27886651
TI  - Foam-Mat Freeze-Drying of Bifidobacterium longum RO175: Viability and
      Refrigerated Storage Stability.
AB  - Foaming as a pretreatment was used prior to freeze-drying of Bifidobacterium
      longum RO175 to investigate the potential acceleration of the drying rate and
      increase in microorganism viability after the process. A study on storage of
      foamed and nonfoamed freeze-dried products at 4  degrees C completed this study.
      B. longum RO175 in foamed medium could be freeze-dried in 1/7 to 1/4 of the time
      required for nonfoamed suspensions. In addition, foamed suspensions presented
      higher viability immediately after freeze-drying (13.6% compared to 12.81 % or
      11.46%, depending on the cryoprotective media). Refrigerated storage led to a
      reduction in B. longum RO175 viability for all tested protective agents (foamed
      and nonfoamed). No correlation between glass transition temperature and stability
      of probiotic powders was observed during storage. In addition, lower viability
      after 56 d of storage was observed for foamed materials, probably due to foam
      porous structure and higher hygroscopicity, and oxygen presence and moisture
      pickup during storage.

PMID- 27886650
TI  - The relationship between gestational age and the severity of neonatal abstinence
      syndrome.
AB  - BACKGROUND AND AIMS: The relationship between gestational age at delivery and the
      severity of neonatal abstinence syndrome (NAS) is poorly understood. Our
      objective was to compare the length of pharmacotherapy and hospital stay among
      opioid-exposed infants born during the late pre-term, early term, full term and
      late term periods. DESIGN: Retrospective cohort study of infants affected by NAS.
      SETTING: MetroHealth Medical Center in Cleveland, OH, USA: an urban tertiary care
      hospital serving as the referral center for opioid dependency in pregnancy with a
      level III neonatal intensive care unit. PARTICIPANTS: All deliveries complicated
      by maternal opioid exposure from January 2000 to October 2014; 403 were eligible
      to be included [n = 102 late pre-term, 34-36 weeks (LP), n = 158 early term, 37
      38 weeks (ET), n = 122 full term, 39-40 weeks (FT), n = 21 late term, >=41 weeks
      (LT)]. MEASUREMENTS: NAS requiring pharmacotherapy with opioids and hospital stay
      duration were compared between gestational age cohorts. Interaction by type of
      maternal medication was evaluated. FINDINGS: The necessity for pharmacotherapy
      for NAS was similar in all gestational age groups [LP n = 45/102 (44%), ET n =
      65/158 (41%), FT n = 55/122 (45%), LT n = 9/21 (43%); P = 0.92]. However, the
      median duration of pharmacotherapy for NAS was significantly different between
      the groups [LP =16.0 median (interquartile range: IQR = 10.0-24.0) days, ET =
      22.5 (IQR = 15.0-40.0), FT = 23.0 (IQR = 6.0-38.0), LT = 22.0 (IQR = 6.0-28.0); P
      = 0.02]. Neonatal intensive care unit admission for NAS (P = 0.07) and total
      length of stay (P = 0.27), which includes observation for NAS not requiring
      medication, were not different. There was no significant interaction between
      gestational age cohorts and maternal medication assisted treatment therapy on the
      need for or duration of NAS treatment. The results were unchanged when evaluated
      for potential confounding variables. CONCLUSIONS: Gestational age (pre-term, term
      or late term) at birth appears to be unrelated to the need for pharmacotherapy to
      treat neonatal abstinence syndrome (NAS) in late pre-term and term infants. If
      treatment is needed it may tend to be given for longer in term than pre-term or
      late term infants.

PMID- 27886652
TI  - Factors associated with short-term transitions of non-daily smokers: socio
      demographic characteristics and other tobacco product use.
AB  - AIMS: To examine the transitions in smoking status among non-daily smokers who
      transitioned to daily or former smokers or remained as non-daily smokers during a
      12-month period. We analyzed factors associated with these transitions, including
      the use of cigars and smokeless tobacco (SLT). DESIGN: Secondary data analyses
      using pooled data from the 2003, 2006/07 and 2010/11 Tobacco Use Supplements to
      the Current Population Survey (TUS-CPS). SETTING: United States. PARTICIPANTS:
      Self-respondents aged 18+ who have smoked for more than 5 years and were non
      daily smokers 12 months before the interview (n = 13 673, or 14.5% of current
      smokers). MEASUREMENTS: Multinomial logistic regression model to determine the
      correlates of non-daily to daily, stable non-daily and non-daily to former
      smoking transitions among non-daily smokers at baseline. The model controlled for
      socio-demographic factors and the use of cigars and SLT. FINDINGS: Of the adults
      in our sample, 2.6% were non-daily smokers at baseline. Among these, 69.7%
      remained non-daily smokers (stable non-daily smokers), 18.4% became daily smokers
      (non-daily to daily smokers) and 11.9% quit smoking (non-daily to former smokers)
      after 12 months. The non-daily to daily versus stable non-daily smoking
      transition was less likely among those who were aged 65+ (P = 0.018), male (P <
      0.001), Hispanic (P < 0.001), with an income of $25 000-49 999 or >=$75 000 and
      current users of SLT (P = 0.003), but more likely among those without a college
      degree compared with the appropriate reference group. The non-daily to former
      versus stable non-daily smoking transition was less likely among those aged 25+,
      male (P = 0.013), non-Hispanic Asian (P = 0.032), without a college degree,
      widowed/divorced/separated (P = 0.013) or never married (P = 0.011) and current
      users of cigars (P = 0.003) compared with the appropriate reference group.
      CONCLUSIONS: While more than two-thirds of non-daily smokers in the United States
      remain as such after 12 months, others become daily smokers or quit. The
      likelihood of remaining stable non-daily smokers and of transition from non-daily
      to daily and non-daily to former smokers is associated with socio-demographic
      factors and current use of cigars and smokeless tobacco.

PMID- 27886653
TI  - Waffle Production: Influence of Baking Plate Material on Sticking of Waffles.
AB  - Background of this study was to understand the factors that contribute to
      sticking of fresh egg waffles on baking plates. The aim of this study was to
      investigate the sticking (adhesion) behavior of waffles on 4 different baking
      plate materials (ductile iron, grey iron, low alloyed steel, and steel with
      titanium nitrite coating) at different baking parameters (temperature and time)
      and application of 3 different release agents (different fat compositions).
      Baking plates from ductile and grey iron showed lower release properties of
      waffles than the 2 steel baking plates. Baking parameters had to be high enough
      to allow rapid product crust formation but prevent burning, which again increases
      sticking behavior. Release agents based on short-chain fatty acids with higher
      degree of saturation provided better release behavior of waffles than those based
      on long-chain fatty acids or on emulsifier-acid combinations. Baking plates with
      increased hardness, good heat storage capacity, and smooth surface seemed to be
      best suitable. Further research on appropriate coating material might be
      promising for future.

PMID- 27886654
TI  - Essential role of K+ uptake permease (Kup) for resistance to sucrose-induced
      stress in Gluconacetobacter diazotrophicus PAl 5.
AB  - Microorganisms are constantly challenged by stressful conditions, such as sugar
      rich environments. Such environments can cause an imbalance of biochemical
      activities and compromise cell multiplication. Gluconacetobacter diazotrophicus
      PAl 5 is among the most sugar-tolerant bacteria, capable of growing in the
      presence of up to 876 mM sucrose. However, the molecular mechanisms involved in
      its response to high sucrose remain unknown. The present work aimed to identify
      sucrose-induced stress resistance genes in G. diazotrophicus PAl 5. Screening of
      a Tn5 transposon insertion library identified a mutant that was severely
      compromised in its resistance to high sucrose concentrations. Molecular
      characterization revealed that the mutation affected the kupA gene, which encodes
      a K+ uptake transporter (KupA). Functional complementation of the mutant with the
      wild type kupA gene recovered the sucrose-induced stress resistance phenotype.
      High sucrose resistance assay, under different potassium concentrations, revealed
      that KupA acts as a high-affinity K+ transporter, which is essential for
      resistance to sucrose-induced stress, when extracellular potassium levels are
      low. This study is the first to show the essential role of the KupA protein for
      resistance to sucrose-induced stress in bacteria by acting as a high-affinity
      potassium transporter in G. diazotrophicus PAl 5.

PMID- 27886655
TI  - Gas Permeability and Permselectivity of Poly(L-Lactic Acid)/SiOx Film and Its
      Application in Equilibrium-Modified Atmosphere Packaging for Chilled Meat.
AB  - A layer of SiOx was deposited on the surface of poly(L-lactic acid) (PLLA) film
      to fabricate a PLLA/SiOx layered film, by plasma-enhanced chemical vapor
      deposition (PECVD) process. PLLA/SiOx film showed Young's modulus and tensile
      strength increased by 119.2% and 91.6%, respectively, over those of neat PLLA
      film. At 5  degrees C, the oxygen (O2 ) and carbon dioxide (CO2 ) permeability of
      PLLA/SiOx film decreased by 78.7% and 71.7%, respectively, and the CO2 /O2
      permselectivity increased by 32.5%, compared to that of the neat PLLA film. When
      the PLLA/SiOx film was applied to the equilibrium-modified atmosphere packaging
      of chilled meat, the gas composition in packaging reached a dynamic equilibrium
      with 6% to 11% CO2 and 8% to 13% O2 . Combined with tea polyphenol pads, which
      effectively inhibited the microbial growth, the desirable color of meat was
      maintained and an extended shelf life of 52 d was achieved for the chilled meat.

PMID- 27886657
TI  - Receipt of addiction treatment as a consequence of a brief intervention for drug
      use in primary care: a randomized trial.
AB  - BACKGROUND AND AIMS: Screening, brief intervention and 'referral to treatment'
      programs have been promoted widely as US federal policy. Little is known about
      the efficacy of the RT component (referral to treatment) of brief intervention
      for motivating patients with unhealthy drug use identified by screening to use
      addiction treatment. This study aimed to compare receipt of addiction treatment
      following two types of brief intervention for drug use versus a no-intervention
      control group among primary care patients screening positive for drug use.
      DESIGN: Secondary analyses from a single-site randomized controlled trial.
      SETTING: Massachusetts, USA. PARTICIPANTS: A total of 528 adults with Alcohol,
      Smoking and Substance Involvement Screening Test (ASSIST) drug-specific scores >=
      4. INTERVENTIONS: Random assignment to: (1) a 10-15-minute brief negotiated
      interview (BNI) conducted by health educators (n = 174), (2) a 30-45-minute
      adaptation of motivational interviewing by Masters-level counselors (MOTIV) (n =
      177) or (3) no BI (n = 177). All received a list of treatment and mutual help
      resources; both intervention protocols included dedicated staff for treatment
      referrals. MEASUREMENTS: Receipt of any addiction treatment within 6 months after
      study entry, assessed in a state-wide database and hospital electronic medical
      record linked to trial data. FINDINGS: Among 528 participants, the main drugs
      used were marijuana (63%), cocaine (19%) and opioids (17%); 46% met past-year
      drug dependence criteria (short form Composite International Diagnostic
      Interview); and 10% of MOTIV, 18% of BNI and 17% of control participants had any
      addiction treatment receipt within 6 months after study entry. There was no
      significant difference in addiction treatment receipt for BNI versus control
      [adjusted odds ratio (AOR) = 1.11; 95% confidence interval (CI) = 0.57, 2.15,
      Hochberg adjusted P = 0.76]. The MOTIV group had lower odds of linking to
      treatment (AOR = 0.36, 95% CI = 0.17, 0.78, Hochberg adjusted P = 0.02) compared
      with the no BI group. CONCLUSION: Brief intervention delivered in primary care
      for screen-identified drug use did not increase addiction treatment receipt
      significantly; a motivational interviewing approach appeared to be
      counterproductive.

PMID- 27886656
TI  - Neural mechanisms underlying visual attention to health warnings on branded and
      plain cigarette packs.
AB  - AIMS: To (1) test if activation in brain regions related to reward (nucleus
      accumbens) and emotion (amygdala) differ when branded and plain packs of
      cigarettes are viewed, (2) test whether these activation patterns differ by
      smoking status and (3) examine whether activation patterns differ as a function
      of visual attention to health warning labels on cigarette packs. DESIGN: Cross
      sectional observational study combining functional magnetic resonance imaging
      (fMRI) with eye-tracking. Non-smokers, weekly smokers and daily smokers performed
      a memory task on branded and plain cigarette packs with pictorial health warnings
      presented in an event-related design. SETTING: Clinical Research and Imaging
      Centre, University of Bristol, UK. PARTICIPANTS: Non-smokers, weekly smokers and
      daily smokers (n = 72) were tested. After exclusions, data from 19 non-smokers,
      19 weekly smokers and 20 daily smokers were analysed. MEASUREMENTS: Brain
      activity was assessed in whole brain analyses and in pre-specified masked
      analyses in the amygdala and nucleus accumbens. On-line eye-tracking during
      scanning recorded visual attention to health warnings. FINDINGS: There was no
      evidence for a main effect of pack type or smoking status in either the nucleus
      accumbens or amygdala, and this was unchanged when taking account of visual
      attention to health warnings. However, there was evidence for an interaction,
      such that we observed increased activation in the right amygdala when viewing
      branded as compared with plain packs among weekly smokers (P = 0.003). When
      taking into account visual attention to health warnings, we observed higher
      levels of activation in the visual cortex in response to plain packaging compared
      with branded packaging of cigarettes (P = 0.020). CONCLUSIONS: Based on
      functional magnetic resonance imaging and eye-tracking data, health warnings
      appear to be more salient on 'plain' cigarette packs than branded packs.

PMID- 27886658
TI  - Identifying in-patient costs attributable to the clinical sequelae and
      comorbidities of alcoholic liver disease in a national hospital database.
AB  - BACKGROUND AND AIMS: The clinical sequelae and comorbidities of alcoholic liver
      disease (ALD) often require hospitalization. The aims of this study were to (1)
      compare the average costs of hospitalizations with ALD and the costs of
      hospitalizations with other alcohol-related diagnoses that do not involve the
      liver; and (2) estimate the percentage of the difference in costs between the ALD
      and non-ALD hospitalizations that may be attributed to ascites, protein-calorie
      malnutrition and other conditions. DESIGN: The 2012 National Inpatient Sample is
      a population-based cross-sectional database representing more than 94% of all
      discharges from community hospitals in the United States. SETTING: Community
      hospitals in the United States. PARTICIPANTS: The sample included 72 531
      hospitalizations with ALD and 287 047 hospitalizations with other alcohol-related
      diagnoses. MEASUREMENTS: The dependent variable was total in-patient costs. We
      estimated the contribution of ascites, protein-calorie malnutrition and other
      conditions to the difference in costs between patients with ALD and patients with
      other diagnoses. FINDINGS: Average costs for ALD patients were $3188.4 higher
      than those for patients with other diagnoses ($13 543 versus $10 355; P < 0.001).
      Among all conditions in the analysis, protein-calorie malnutrition had the
      largest impact on costs [$6501; 95% confidence interval (CI) = 5956, 7045; P <
      0.001] accounting for 12% of the higher costs of ALD stays. CONCLUSIONS: Costs of
      hospital care for patients with alcoholic liver disease are higher than those for
      patients with other alcohol-related diagnoses. These increased costs are
      associated with specific clinical sequelae and comorbidities, with protein
      calorie malnutrition-a largely preventable condition-making a substantial
      contribution.

PMID- 27886659
TI  - Physicochemical and Mechanical Properties of Bambara Groundnut Starch Films
      Modified with Stearic Acid.
AB  - The physicochemical and mechanical properties of biofilm prepared from bambara
      starch modified with varying concentrations of stearic acid (0%, 2.5%, 3.5%, 5%,
      7%, and 10%) were studied. By scanning electron microscopy, bambara starch films
      modified with stearic acid (>=3.5%) showed a progressively rough surface compared
      to those with 2.5% stearic acid and the control. Fourier transform infrared
      spectroscopy spectra revealed a peak shift of approximately 31 cm-1 , suggesting
      the promotion of hydrogen bond formation between hydroxyl groups of starch and
      stearic acid. The addition of 2.5% stearic acid to bambara starch film reduced
      water vapor permeability by approximately 17%. Bambara starch films modified with
      higher concentration of stearic acid were more opaque and showed significantly
      high melting temperatures. However, mechanical properties of starch films were
      generally negatively affected by stearic acid. Bambara starch film may be
      modified with 2.5% stearic acid for improved water vapor permeability and thermal
      stability with minimal effect on tensile strength.

PMID- 27886661
TI  - Bacterial diversity shift determined by different diets in the gut of the spotted
      wing fly Drosophila suzukii is primarily reflected on acetic acid bacteria.
AB  - The pivotal role of diet in shaping gut microbiota has been evaluated in
      different animal models, including insects. Drosophila flies harbour an
      inconstant microbiota among which acetic acid bacteria (AAB) are important
      components. Here, we investigated the bacterial and AAB components of the
      invasive pest Drosophila suzukii microbiota, by studying the same insect
      population separately grown on fruit-based or non-fruit artificial diet. AAB were
      highly prevalent in the gut under both diets (90 and 92% infection rates with
      fruits and artificial diet respectively). Fluorescent in situ hybridization and
      recolonization experiments with green fluorescent protein (Gfp)-labelled strains
      showed AAB capability to massively colonize insect gut. High-throughput
      sequencing on 16S rRNA gene indicated that the bacterial microbiota of guts fed
      with the two diets clustered separately. By excluding AAB-related OTUs from the
      analysis, insect bacterial communities did not cluster separately according to
      the diet, suggesting that diet-based diversification of the community is
      primarily reflected on the AAB component of the community. Diet influenced also
      AAB alpha-diversity, with separate OTU distributions based on diets. High
      prevalence, localization and massive recolonization, together with AAB clustering
      behaviour in relation to diet, suggest an AAB role in the D. suzukii gut response
      to diet modification.

PMID- 27886660
TI  - Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O
      mutant on the humoral response to dengue virus antigens.
AB  - Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant
      molecule in the vaccination field. However, the cytotoxic and pro-apoptotic
      effects of LLO are the major limitations for this purpose. Here, we have
      performed a preclinical safety evaluation and characterized a new potential
      adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and
      modulate the immune response against the envelope (E) protein from dengue virus.
      In addition, we have studied the adjuvant effects of dtLLO on human immune cells
      and the role of membrane cholesterol for the binding and proinflammatory property
      of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a
      safer molecule than wild-type LLO (wtLLO), with a significantly increased
      survival rate for mice challenged with dtLLO compared with mice challenged with
      wtLLO (P < 0.001). Histopathological analysis showed non-toxic effects in key
      target organs such as brain, heart, liver, spleen, kidney and lung after
      challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma
      membrane cholesterol on the surface of murine and human immune cells.
      Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed
      with E protein elicited a robust specific humoral response with isotype
      diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we
      demonstrated that cholesterol and lipid raft integrity are required to induce a
      proinflammatory response by human cells. Taken together, these findings support a
      potential use of the dtLLO mutant as a safe and effective adjuvant molecule in
      vaccination.

PMID- 27886662
TI  - Osteoblast response to the surface topography of hydroxyapatite two-dimensional
      films.
AB  - In the current study, three hydroxyapatite two-dimensional films with similar
      wettability but different topological roughness have been prepared through a
      facile one-step method using hydrated polylactic acid discs as substrates. The
      results indicated that the protein adsorption capabilities of the hydroxyapatite
      two-dimensional films and the proliferation of osteoblast cells on the as
      prepared films increased obviously with the increase of the films' roughness.
      These reveal that the cellular responses to two-dimensional materials can be
      efficiently tuned by easily adjusting the topological roughness. This finding
      affords an efficient strategy to regulate the cellular response to bioinorganic
      two-dimensional materials and significantly expanded their application potentials
      in tissue engineering. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 105A: 991-999, 2017.

PMID- 27886663
TI  - Organic impurity profiling of methylone and intermediate compounds synthesized
      from catechol.
AB  - This work examined the synthesis and organic impurity profile of methylone
      prepared from catechol. The primary aim of this work was to determine whether the
      synthetic pathway used to prepare 3,4-methylenedioxypropiophenone could be
      ascertained through analysis of the synthesized methylone. The secondary aim was
      the structural elucidation and origin determination of the organic impurities
      detected in methylone and the intermediate compounds. The organic impurities
      present in the reaction products were identified using GC-MS and NMR
      spectroscopy. Six organic impurities were detected in 1,3-benzodioxole and
      identified as the 1,3-benzodioxole dimer, 1,3-benzodioxole trimer, [1,3]
      dioxolo[4,5-b]oxanthrene, 4,4'-, 4,5'-, and 5,5'-methylenebis-1,3-benzodioxole.
      Six organic impurities were detected in 3,4-methylenedioxypropiophenone and
      identified as (2-hydroxyphenyl) propanoate, [2-(chloromethoxy) phenyl]
      propanoate, (2-propanoyloxyphenyl)propanoate, 5-[1-(1,3-benzodioxol-5-yl)prop-1
      enyl]-1,3-benzodioxole, (5E)- and (5Z)-7-(1,3-benzodioxol-5-yl)-5-ethylidene-6
      methyl-cyclopenta[f][1,3]benzodioxole). Exploratory synthetic experiments were
      also conducted to unambiguously identify the organic impurities detected in 3,4
      methylenedioxypropiophenone. Two organic impurities were detected in 5-bromo-3,4
      methylenedioxypropiophenone and identified as [2-(chloromethoxy)phenyl]
      propanoate and 3,4-methylenedioxypropiophenone. Five organic impurities were
      detected in methylone and identified as 3,4-methylenedioxypropiophenone, 1-(1,3
      benzodioxol-5-yl)-N-methyl-propan-1-imine, 1-(1,3-benzodioxol-5-yl)-2-methylimino
      propan-1-one, 1-(1,3-benzodioxol-5-yl)-N1,N2-dimethyl-propane-1,2-diimine and
      butylated hydroxytoluene. The origin of these organic impurities was also
      ascertained, providing valuable insight into the chemical profiles of methylone
      and the intermediate compounds. However, neither the catechol precursor nor the
      1,3-benzodioxole intermediate could be identified based on the organic impurities
      detected in the synthesized methylone using standard techniques. This
      demonstrated that the organic impurity profiling of methylone had limitations in
      the determination of precursor chemical and synthetic pathways used. Copyright
      (c) 2017 John Wiley & Sons, Ltd.

PMID- 27886665
TI  - ?

PMID- 27886664
TI  - Degradation behaviors of geometric cues and mechanical properties in a 3D
      scaffold for tendon repair.
AB  - A three-dimensional (3D) scaffold fabricated via electrohydrodynamic jet printing
      (E-jetting) and thermally uniaxial stretching, has been developed for tendon
      tissue regeneration in our previous study. In this study, more in-depth
      biological test showed that the aligned cell morphology guided by the anisotropic
      geometries of the 3D tendon scaffolds, leading to up-regulated tendious gene
      expression including collagen type I, decorin, tenascin-C, and biglycan, as
      compared to the electrospun scaffolds. Given the importance of geometric cues to
      the biological function of the scaffolds, the degradation behaviors of the 3D
      scaffolds were investigated. Results from accelerated hydrolysis showed that the
      E-jetted portion followed bulk-controlled erosion, while the unaixially stretched
      portion followed surface-controlled erosion. The 3D tendon scaffold exhibited
      consistency between the weight loss and the decline of mechanical properties,
      which indicated by a 65% decrease in mass with a corresponding 56% loss in
      ultimate tensile strength after degradation. This study not only reveals that the
      anisotropic geometries of 3D tendon scaffold could affect cell morphology and
      lead to desired gene expression toward tendon tissue but also gives an insight
      into how the degradation impacts geometric cues and mechanical properties of the
      as-fabricated scaffold. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 105A: 1138-1149, 2017.

PMID- 27886666
TI  - Nurse scientist or nursing scientist: Future considerations for the field.

PMID- 27886667
TI  - Membrane Lipid Galore.

PMID- 27886668
TI  - A new definition for oral health developed by the FDI World Dental Federation
      opens the door to a universal definition of oral health.

PMID- 27886669
TI  - Revising the American Dental Association Principles of Ethics and Code of
      Professional Conduct: Adding "Respect for Human Dignity" as the sixth principle
      of dental ethics to accommodate advances in genetic science.

PMID- 27886670
TI  - Negotiating Payment Rates.

PMID- 27886671
TI  - No clinically significant differences in crestal bone loss between immediate
      implant placement and implants placed in healed bone: A systematic review of
      articles published from 1966 through 2012.

PMID- 27886672
TI  - How to get your staff members on board.

PMID- 27886673
TI  - In silico, in vitro and case-control analyses as an effective combination for
      analyzing BRCA1 and BRCA2 unclassified variants in a population-based sample.
AB  - Ascertaining the clinical consequences of BRCA1 and BRCA2 variants of uncertain
      significance (VUS) is currently indispensable for providing effective genetic
      counseling and preventive actions for families with hereditary breast and ovarian
      cancer (HBOC). To this end, we conducted a combination of in silico prediction
      and cDNA splicing analyses of 13 BRCA1 and 10 BRCA2 VUS identified in our cohort
      as well as a case-control analysis in a population-based sample of 10 recurrent
      VUS. We observed consistent results between the in silico predictions and
      sequencing analyses for all analyzed VUS. An abnormal cDNA pattern was observed
      for variants c.212+1G>A and c.5278-1G>A in BRCA1 and c.516+2T>A and c.8168A>G in
      BRCA2 according to in silico splicing prediction. A case-control study of VUS
      confirmed the polymorphisms of the c.67+62A>G, c.7008-62A>G and c.8851G>A BRCA2
      variants previously published. c.4068G>A in the BRCA2 gene can also be considered
      a polymorphism due to its occurrence at a frequency greater than 1% in our
      population. Our study shows that employing population-based analysis and a
      combination of several in silico methods yields highly accurate information,
      resulting in a reliable tool for selecting variants for cDNA sequencing analysis
      in routine cancer genetic counseling units.

PMID- 27886674
TI  - Pri-miR-34b/c rs4938723 polymorphism is associated with the risk of childhood
      acute lymphoblastic leukemia.
AB  - MicroRNAs (miRNAs), small noncoding regulatory RNAs, are key regulators of gene
      expression. The impact of Pri-miR-34b/c rs4938723 variant on development of
      various cancers is still controversial. In the present study, we examined whether
      a rs4938723 variant located at the promoter region of Pri-miR-34b/c is associated
      with childhood ALL. A total of 110 children with acute lymphoblastic leukemia
      (ALL) and 120 healthy children were recruited to participate in this study. The
      rs4938723 variant was genotyped by polymerase chain reaction restriction fragment
      length polymorphism (PCR-RFLP) method. The rs4938723 variant decreased the risk
      of ALL in heterozygous (TC vs OR = 0.48, 95% CI = 0.28-0.84, p = 0.012, TC vs TT)
      and overdominant (OR = 0.51, 95% CI = 0.30-0.89, p = 0.0.020, TC vs TT + CC): OR
      = 1.32, 95% CI = 0.67-2.59, p = 0.498; C vs T: OR = 0.99, 95% CI = 0.75-1.31, p =
      0.986) inheritance models tested. The C allele significantly decreased the risk
      of childhood ALL compared to T allele (OR = 0.52, 95% CI = 0.33-0.83, p = 0.006).
      Our findings proposed an association between Pri-miR-34 b/c rs4938723 variant and
      risk of childhood ALL development in a sample of Iranian population.

PMID- 27886675
TI  - Pathogenic germline MCM9 variants are rare in Australian Lynch-like syndrome
      patients.
AB  - Lynch syndrome is a hereditary cancer syndrome caused by the autosomal dominant
      inheritance of loss-of-function mutations in DNA mismatch repair (MMR) genes.
      Approximately one quarter of clinically suspected cases have no identifiable
      germline mutation in any MMR gene, a condition known as Lynch-like syndrome
      (LLS). MCM9 was recently identified as the DNA helicase in the mammalian MMR
      complex and loss of helicase activity results in microsatellite instability. We
      hypothesized that pathogenic variants in MCM9 may account for LLS. The 5'UTR and
      coding region of MCM9 were sequenced in germline DNA of 109 Australian patients
      with LLS and variants were cross-referenced with three population-based databases
      (dbSNP144, 1000 Genomes, ExAC). The functional effect of variants was assessed in
      silico with PolyPhen-2, SIFT and CONDEL. Fifteen variants that included six
      common SNPs and nine variants of unknown significance (VUS) were identified. We
      conclude that VUS occur in MCM9 in a small proportion of LLS patients and MCM9
      mutations are unlikely to explain most LLS cases.

PMID- 27886676
TI  - Chromosomal rearrangements in myoepithelial carcinoma of the breast that
      presented as metachronic double cancer with invasive ductal carcinoma in the
      ipsilateral breast.
AB  - Myoepithelial carcinoma of the breast is an extremely rare tumor composed
      entirely of malignant spindle cells with myoepithelial differentiation. The
      majority of previously reported cases have mainly described the
      clinicopathological features of the disease, and few have presented cytogenetic
      data. We herein present the case of a 48-year-old woman who was admitted with a
      left-sided breast lump in the inner upper quadrant that was initially diagnosed
      as a myoepithelioma with potentially malignant disorder. At 12 months after
      resection, she complained about a newly developed solid mass in the subareolar
      region of the ipsilateral breast that was diagnosed as an invasive ductal
      carcinoma. In addition, 16 months after the initial admission, a re-growing
      remnant lesion recurred in the inner upper quadrant and was ultimately diagnosed
      as a myoepithelial carcinoma. Lymph node metastasis of the myoepithelial
      carcinoma was also observed in her left axillary region 11 months after local
      recurrence. A cytogenetic analysis showed recurring specific chromosomal
      alterations both in the locally recurrent and in the lymph-node metastatic
      lesion: 48, XX, t(5;18)(q13;q23),del(6)(q?),+14. + mar1. To our knowledge, this
      is the first published report of clonal chromosomal rearrangements in
      myoepithelial carcinoma of the breast that presented as metachronic double cancer
      with invasive ductal carcinoma in the ipsilateral breast.

PMID- 27886678
TI  - Role of Patellofemoral Offset in Total Knee Arthroplasty: A Randomized Trial.
AB  - Total knee arthroplasty occasionally does not meet expectations. This randomized
      clinical trial assessed the effect of restoration of the native patellofemoral
      height on clinical outcomes. Group I underwent standard patellar bone resection;
      group II underwent modified patellar bone resection that adjusted the amount of
      anterior condylar bone removed and the anterior flange thickness. There were no
      differences in anterior knee pain, Western Ontario and McMaster Universities
      Arthritis Index scores, or Knee Injury and Osteoarthritis Outcome Score scores.
      Patellofemoral compartment height restoration versus patellar height alone does
      not appear to significantly reduce pain or improve function.

PMID- 27886677
TI  - Differences in global DNA methylation of testicular seminoma are not associated
      with changes in histone modifications, clinical prognosis, BRAF mutations or gene
      expression.
AB  - Testicular germ cell tumours of young adults are comprised of a heterogeneous
      group of non-seminomas and a homogeneous group of seminomas. While the majority
      of seminomas retain a hypo-methylated genome, a small fraction displays a highly
      methylated genome, resembling hyper-methylated non-seminomas. It is well
      established from e.g. melanoma, colorectal and thyroid cancer that a methylated
      phenotype can be correlated to prognosis and can be related to BRAF mutations. In
      the present study we investigated the global methylation level in 67 seminomas
      and classified them as hypo-methylated, intermediate, patchy and hyper
      methylated, respectively. A selected subset representing each level of DNA
      methylation and the TCam2 seminoma cell line were subsequently analysed for a
      range of other epigenetic marks (6 histone marks and 5-hydroxymethylcytosine),
      the presence of the BRAF V600E de novo mutation, differences in the transcriptome
      and finally correlated to the clinical outcome. We did not identify any histone
      marks or hydroxymethylation levels that correlated with the methylation level of
      the genome. Some histone marks, however, showed a great variation while others
      were found at the same level in all the investigated seminomas. We did not
      identify any tumours with the BRAF V600E mutation and transcriptome analysis
      revealed no significant differences between hypo- and hyper-methylated seminomas.
      Similarly, no obvious differences in the clinical manifestation of the patients
      representing hypo- or hyper-methylated seminomas were identified. The level of
      DNA methylation in testicular seminomas consequently seems secondary to the
      manifestation of the tumour phenotype.

PMID- 27886679
TI  - Impact of Inpatient Versus Outpatient Total Joint Arthroplasty on 30-Day Hospital
      Readmission Rates and Unplanned Episodes of Care.
AB  - This article describes a study comparing 30-day readmission rates between
      patients undergoing outpatient versus inpatient total hip (THA) and knee (TKA)
      arthroplasty. A retrospective review of 137 patients undergoing outpatient total
      joint arthroplasty (TJA) and 106 patients undergoing inpatient (minimum 2-day
      hospital stay) TJA was conducted. Unplanned hospital readmissions and unplanned
      episodes of care were recorded. All patients completed a telephone survey. Seven
      inpatients and 16 outpatients required hospital readmission or an unplanned
      episode of care following hospital discharge. Readmission rates were higher for
      TKA than THA. The authors found no statistical differences in 30-day readmission
      or unplanned care episodes.

PMID- 27886680
TI  - Timing of Operative Debridement in Open Fractures.
AB  - The optimal treatment of open fractures continues to be an area of debate in the
      orthopedic literature. Recent research has challenged the dictum that open
      fractures should be debrided within 6 hours of injury. However, the expedient
      administration of intravenous antibiotics remains of paramount importance in
      infection prevention. Multiple factors, including fracture severity, thoroughness
      of debridement, time to initial treatment, and antibiotic administration, among
      other variables, contribute to the incidence of infection and complicate
      identifying an optimal time to debridement.

PMID- 27886681
TI  - Heterotopic Ossification in Trauma.
AB  - Better understanding of the biology of heterotopic ossification (HO) formation
      will lead to treatment and prevention modalities that can be directed
      specifically at the cellular level. Early identification of HO precursor cells
      and target genes may provide prognostic value that guides individualized
      prophylactic treatment. Better understanding of molecular signaling and
      proteomics variability will allow surgeons to individualize preemptive treatment
      to suppress inflammation and formation of HO. Careful surgical technique to avoid
      muscle damage is important. Damaged muscle should be debrided as a prophylactic
      measure. Hemostasis and avoidance of a postoperative hematoma may decrease the
      chance of formation of HO.

PMID- 27886682
TI  - Clavicle Shaft Fractures in Adolescents.
AB  - Midshaft clavicle fractures in adolescents are common. Recent literature in
      adults fractures favors open reduction and plate fixation for significantly
      displaced and/or shortened midshaft clavicle fractures, although whether this
      applies to adolescents remains debatable. This article reviews the current
      literature and controversy in the management of displaced adolescent clavicle
      fractures.

PMID- 27886683
TI  - Complications of Pediatric Foot and Ankle Fractures.
AB  - Ankle fractures account for 5% and foot fractures account for approximately 8% of
      fractures in children. Some complications are evident early in the treatment or
      natural history of foot and ankle fractures. Other complications do not become
      apparent until weeks, months, or years after the original fracture. The incidence
      of long-term sequelae like posttraumatic arthritis from childhood foot and ankle
      fractures is poorly studied because decades or lifelong follow-up has frequently
      not been accomplished. This article discusses a variety of complications
      associated with foot and ankle fractures in children or the treatment of these
      injuries.

PMID- 27886684
TI  - Controversies in Fractures of the Proximal Ulna.
AB  - The olecranon process, coronoid process, and greater sigmoid notch are important
      components of the complex proximal ulna. Along with providing bony stability to
      the ulnohumeral joint, the proximal ulna serves as the attachment site of many
      important muscles and ligaments that impart soft tissue stability to the elbow
      joint. Management of proximal ulnar fractures continues to evolve as advances in
      imaging and anatomic and biomechanical studies have led to improvements in
      available implants; however, controversies remain, as shown in the current
      relevant literature.

PMID- 27886685
TI  - Posterior Malleolus Fractures.
AB  - Posterior malleolus fractures vary in morphology. A computed tomography scan is
      imperative to evaluate fragment size, comminution, articular impaction, and
      syndesmotic disruption. Despite an increasing body of literature regarding
      posterior malleolus fractures, many questions remain unanswered. Although,
      historically, fragment size guided surgical fixation, it is becoming evident that
      fragment size should not solely dictate treatment. Surgical treatment should
      focus on restoring ankle joint structural integrity, which includes restoring
      articular congruity, correcting posterior talar translation, addressing articular
      impaction, removing osteochondral debris, and establishing syndesmotic stability.

PMID- 27886686
TI  - Preoperative Versus Postoperative Initiation of Warfarin Therapy in Patients
      Undergoing Total Hip and Knee Arthroplasty.
AB  - The optimal strategy for postoperative deep venous thrombosis prophylaxis remains
      controversial in hip and knee arthroplasty. Warfarin causes transient
      hypercoagulability; however, the optimal timing of treatment remains unclear. We
      evaluated the effects of preoperative versus postoperative warfarin therapy with
      a primary endpoint of perioperative change in hemoglobin. Warfarin was dosed
      according to a standard nomogram. No difference in perioperative hemoglobin
      change was observed. The preoperative group demonstrated higher INRs. Initiation
      of warfarin preoperatively was not associated with any difference in
      perioperative hemoglobin change. Larger studies are needed to determine whether
      the risk of adverse events is increased with either strategy.

PMID- 27886687
TI  - Current Controversies in Management of Calcaneus Fractures.
AB  - Displaced intraarticular fractures of the calcaneus represent a technically
      challenging injury. Although there is conflicting evidence regarding advantages
      and disadvantages of operative versus nonoperative treatment, a growing body of
      literature suggests operative management with near-anatomic reduction of the
      posterior facet and restoration of overall calcaneal morphology offers greater
      potential for superior short- and long-term outcomes. A thorough understanding of
      calcaneal anatomy, fracture pattern, and associated injuries, along with careful
      selection of surgical approach and timing to surgery are critical to minimize the
      risk of complication and maximize potential for optimal outcomes.

PMID- 27886688
TI  - Controversies in Fracture Care.

PMID- 27886689
TI  - Invited Commentary: Misreading Between the Lines.

PMID- 27886691
TI  - Pharmacotherapy Pearls for the Geriatrician: Focus on Oral Disease-Modifying
      Antirheumatic Drugs Including Newer Agents.
AB  - Providing safe and effective pharmacotherapy to the geriatric patients with
      rheumatological disorders is an ongoing struggle for the rheumatologist and
      geriatrician alike. Cohesive communication and partnership can improve the care
      of these patients and subvert adverse outcomes. Disease-modifying antirheumatic
      drugs, including methotrexate, hydroxychloroquine, sulfasalazine, and
      leflunomide, and the newest oral agent for treatment of rheumatoid arthritis,
      tofacitinib, have distinctive monitoring and adverse effect profiles. This
      article provides the general practitioner or geriatrician with clinically
      relevant pearls regarding the use of these interventions in older patients.

PMID- 27886692
TI  - Cardiovascular Disease Risk in Patients with Rheumatic Diseases.
AB  - Evidence suggests the greater than 1.5 increased risk of cardiovascular disease
      (CVD) in rheumatoid arthritis (RA) is related to an accelerated burden of
      subclinical atherosclerosis that develops before the diagnosis of RA.
      Dyslipidemia in RA is better quantified by lipoproteins and apolipoproteins than
      cholesterol levels. Current risk factors likely underestimate CVD risk partly by
      underestimating prior risk factor levels. To reduce CVD risk in RA, control
      disease activity and aggressively treat CVD risk factors. Some of the two-fold
      higher risk of heart failure and total mortality in RA may be due to myocardial
      disease caused by inflammation.

PMID- 27886694
TI  - Update on Crystal-Induced Arthritides.
AB  - The prevalence of gout increases with age. Once serum concentration of urate
      exceeds the saturation/solubility point, it deposits in and around the joints.
      Clinical presentation in the elderly often has "atypical" features and is
      challenging to diagnose. Treatment depends on the stage of the disease and the
      patient's health status and comorbidities. Elderly patients often have several
      confounding issues; thus, treatment decisions can be complicated and therapeutic
      options limited. To prevent the recurrence of gout attacks, serum concentration
      of urate should be maintained well below the saturation threshold of 6.8 mg/dL,
      leading to dissolution of urate deposits and prevent recurrence.

PMID- 27886693
TI  - Gaps in Aging Research as it Applies to Rheumatologic Clinical Care.
AB  - The incidence and prevalence of rheumatologic conditions are increasing and the
      rheumatology workforce must be aware of aging-specific issues. This article
      reviews specific barriers to understanding the biology of aging and aging-related
      mechanisms that may underlie development of rheumatologic diseases in older
      adults. It summarizes gaps in the assessment, outcomes measurement, and treatment
      of these diseases in this unique population. It also highlights potential
      solutions to these barriers and suggests possible ways to bridge the gap, from a
      research and education standpoint, so that clinicians can be better prepared to
      effectively manage older adults with rheumatologic conditions.

PMID- 27886696
TI  - A Review of Osteoporosis in the Older Adult.
AB  - Osteoporosis in the elderly population is common. It results in more than 1.5
      million fractures per year in the United States. The goal of managing
      osteoporosis is to prevent fractures. In men, osteoporosis is underrecognized and
      undertreated. More men than women die every year as a consequence of hip
      fractures. A review of diagnosis and treatment of osteoporosis is described in
      this article. Bisphosphonates are the first-line treatment for men and women. In
      the past several years, advances in bone biology have resulted in major
      therapeutic advances.

PMID- 27886695
TI  - Pathogenesis and Management of Sarcopenia.
AB  - Sarcopenia represents a loss of muscle strength and mass in older individuals.
      Sarcopenia in the elderly has now become a major focus of research and public
      policy debate due to its impact on morbidity, mortality, and health care
      expenditure. Despite its clinical importance, sarcopenia remains under-recognized
      and poorly managed in routine clinical practice. This is, in part, due to a lack
      of available diagnostic testing and uniform diagnostic criteria. The management
      of sarcopenia is primarily focused on physical therapy for muscle strengthening
      and gait training. There are no pharmacologic agents for the treatment of
      sarcopenia.

PMID- 27886697
TI  - Nonsurgical Management of Osteoarthritis Knee Pain in the Older Adult.
AB  - Symptomatic knee osteoarthritis is a common complaint of many elderly patients in
      primary care offices. For those unable or unwilling to undergo knee replacement,
      the primary practitioners' understanding of the strengths and weaknesses of the
      available treatment modalities for pain relief is critical to successful in
      office counseling and expectation management. Treatment requires a multimodal
      approach of nonpharmacologic and pharmacologic therapies to achieve a maximal
      clinical benefit. The focus of this review is on the nonsurgical options for
      treatment of knee osteoarthritis in patients aged 65 and older.

PMID- 27886698
TI  - Regional Rheumatic Disorders and Rehabilitation in Older Adults.
AB  - Musculoskeletal problems are the most frequently reported complaints among older
      adults living in the community. The impact of the aging process on skeletal
      muscles and joints can have a profound effect on the ability of individuals with
      and without disabilities to function. This article reviews the rehabilitation
      medicine approach to the evaluation of older adults with regional rheumatic
      disorders, and the rehabilitation medicine considerations for clinical
      interventions. Future research considerations are encouraged in order to gain a
      greater understanding of the subject matter and its impact on the provision of
      care and patients' quality of life.

PMID- 27886699
TI  - Rheumatologic Manifestations of Malignancy.
AB  - A variety of conditions mimicking rheumatologic syndromes may be associated with
      an underlying malignancy. Therefore, distinguishing these syndromes from more
      common, nonparaneoplastic rheumatologic conditions can be perplexing. Some
      autoimmune conditions and the medications used for their management can be
      associated with increased future risk of malignancy. Some cancers can directly
      involve the musculoskeletal structures, whereas others present with systemic
      manifestations at sites away from the tumor and its metastases. Better awareness
      and timely recognition of these associations may lead to earlier cancer detection
      and hopefully better long-term survival.

PMID- 27886701
TI  - Rheumatic Diseases in Older Adults.

PMID- 27886703
TI  - Science-The Cornerstone of Nutrition Policy, Promotion, and Practice.

PMID- 27886702
TI  - The Academy's Millennial Generation.

PMID- 27886700
TI  - Sjogren Syndrome and Other Causes of Sicca in Older Adults.
AB  - Dry eye and dry mouth symptoms are each reported by up to 30% of persons more
      than 65 years of age, particularly in women. Medication side effects are the most
      common contributing factors. The evaluation of these symptoms requires measures
      of ocular and oral dryness. Sjogren syndrome is the prototypic disease associated
      with dryness of the eyes and mouth and predominantly affects women in their
      perimenopausal and postmenopausal years. In addition to topical treatment of the
      mucosal dryness, patients with Sjogren syndrome may require treatment with
      systemic immunomodulatory and immunosuppressive agents to manage a variety of
      extraglandular manifestations.

PMID- 27886704
TI  - Position of the Academy of Nutrition and Dietetics: Vegetarian Diets.
AB  - It is the position of the Academy of Nutrition and Dietetics that appropriately
      planned vegetarian, including vegan, diets are healthful, nutritionally adequate,
      and may provide health benefits for the prevention and treatment of certain
      diseases. These diets are appropriate for all stages of the life cycle, including
      pregnancy, lactation, infancy, childhood, adolescence, older adulthood, and for
      athletes. Plant-based diets are more environmentally sustainable than diets rich
      in animal products because they use fewer natural resources and are associated
      with much less environmental damage. Vegetarians and vegans are at reduced risk
      of certain health conditions, including ischemic heart disease, type 2 diabetes,
      hypertension, certain types of cancer, and obesity. Low intake of saturated fat
      and high intakes of vegetables, fruits, whole grains, legumes, soy products,
      nuts, and seeds (all rich in fiber and phytochemicals) are characteristics of
      vegetarian and vegan diets that produce lower total and low-density lipoprotein
      cholesterol levels and better serum glucose control. These factors contribute to
      reduction of chronic disease. Vegans need reliable sources of vitamin B-12, such
      as fortified foods or supplements.

PMID- 27886705
TI  - The Commission on Dietetic Registration: Ahead of the Trends for a Competent 21st
      Century Workforce.

PMID- 27886706
TI  - Erratum.

PMID- 27886707
TI  - What Strategies do Registered Dietitian Nutritionists Use to Assess a
      Patient's/Client's Weight Loss Readiness?

PMID- 27886708
TI  - Individual tooth segmentation from CT images scanned with contacts of maxillary
      and mandible teeth.
AB  - BACKGROUND AND OBJECTIVE: Tooth segmentation from computed tomography (CT) images
      is a fundamental step in generating the three-dimensional models of tooth for
      computer-aided orthodontic treatment. Individual tooth segmentation from CT
      images scanned with contacts of maxillary and mandible teeth is especially
      challenging, and no method has been reported previously. This study aimed to
      develop a method for individual tooth segmentation from these images. METHODS:
      Tooth contours of maxilla and mandible are first segmented from the volumetric CT
      images slice-by-slice. For each slice, a line is extracted using the Radon
      transform to separate neighboring teeth, and each tooth contour is then segmented
      by a level set model from the corresponding side of the line. Then, each
      maxillary tooth whose contours overlap with that of mandible ones is detected,
      and a mesh model is reconstructed from all the contours of these maxillary and
      mandible teeth with contour overlap. The reconstructed mesh model is segmented
      using threshold and fast marching watershed method to separate the touched
      maxillary and mandible teeth. Finally, the separated tooth models are restored to
      fill the holes to obtain complete tooth models. The proposed method was tested on
      CT images of ten subjects scanned with natural contacts of maxillary and mandible
      teeth. RESULTS: For all the tested images, individual tooth regions are extracted
      successfully, and the segmentation accuracy and efficiency of the proposed method
      is promising. CONCLUSIONS: The proposed method is effective to segment individual
      tooth from CT images scanned with contacts of maxillary and mandible teeth.

PMID- 27886709
TI  - A computer tool for a minimax criterion in binary response and heteroscedastic
      simple linear regression models.
AB  - BACKGROUND AND OBJECTIVE: Binary response models are used in many real
      applications. For these models the Fisher information matrix (FIM) is
      proportional to the FIM of a weighted simple linear regression model. The same is
      also true when the weight function has a finite integral. Thus, optimal designs
      for one binary model are also optimal for the corresponding weighted linear
      regression model. The main objective of this paper is to provide a tool for the
      construction of MV-optimal designs, minimizing the maximum of the variances of
      the estimates, for a general design space. METHODS: MV-optimality is a
      potentially difficult criterion because of its nondifferentiability at equal
      variance designs. A methodology for obtaining MV-optimal designs where the design
      space is a compact interval [a, b] will be given for several standard weight
      functions. RESULTS: The methodology will allow us to build a user-friendly
      computer tool based on Mathematica to compute MV-optimal designs. Some
      illustrative examples will show a representation of MV-optimal designs in the
      Euclidean plane, taking a and b as the axes. The applet will be explained using
      two relevant models. In the first one the case of a weighted linear regression
      model is considered, where the weight function is directly chosen from a typical
      family. In the second example a binary response model is assumed, where the
      probability of the outcome is given by a typical probability distribution.
      CONCLUSIONS: Practitioners can use the provided applet to identify the solution
      and to know the exact support points and design weights.

PMID- 27886710
TI  - Automated diagnosis of coronary artery disease (CAD) patients using optimized
      SVM.
AB  - BACKGROUND AND OBJECTIVE: Currently Coronary Artery Disease (CAD) is one of the
      most prevalent diseases, and also can lead to death, disability and economic loss
      in patients who suffer from cardiovascular disease. Diagnostic procedures of this
      disease by medical teams are typically invasive, although they do not satisfy the
      required accuracy. METHODS: In this study, we have proposed a methodology for the
      automatic diagnosis of normal and Coronary Artery Disease conditions using Heart
      Rate Variability (HRV) signal extracted from electrocardiogram (ECG). The
      features are extracted from HRV signal in time, frequency and nonlinear domains.
      The Principal Component Analysis (PCA) is applied to reduce the dimension of the
      extracted features in order to reduce computational complexity and to reveal the
      hidden information underlaid in the data. Finally, Support Vector Machine (SVM)
      classifier has been utilized to classify two classes of data using the extracted
      distinguishing features. In this paper, parameters of the SVM have been optimized
      in order to improve the accuracy. RESULTS: Provided reports in this paper
      indicate that the detection of CAD class from normal class using the proposed
      algorithm was performed with accuracy of 99.2%, sensitivity of 98.43%, and
      specificity of 100%. CONCLUSIONS: This study has shown that methods which are
      based on the feature extraction of the biomedical signals are an appropriate
      approach to predict the health situation of the patients.

PMID- 27886711
TI  - EEG epochs with less alpha rhythm improve discrimination of mild Alzheimer's.
AB  - BACKGROUND AND OBJECTIVE: Eyes-closed-awake electroencephalogram (EEG) is a
      useful tool in the diagnosis of Alzheimer's. However, there is eyes-closed-awake
      EEG with dominant or rare alpha rhythm. In this paper, we show that random
      selection of EEG epochs disregarding the alpha rhythm will lead to bias
      concerning EEG-based Alzheimer's Disease diagnosis. METHODS: We compared EEG
      epochs with more than 30% and with less than 30% alpha rhythm of mild Alzheimer's
      Disease patients and healthy elderly. We classified epochs as dominant alpha
      scenario and rare alpha scenario according to alpha rhythm (8-13 Hz) percentage
      in O1, O2 and Oz channels. Accordingly, we divided the probands into four groups:
      17 dominant alpha scenario controls, 15 mild Alzheimer's patients with dominant
      alpha scenario epochs, 12 rare alpha scenario healthy elderly and 15 mild
      Alzheimer's Disease patients with rare alpha scenario epochs. We looked for group
      differences using one-way ANOVA tests followed by post-hoc multiple comparisons
      (p < 0.05) over normalized energy values (%) on the other four well-known
      frequency bands (delta, theta, beta and gamma) using two different electrode
      configurations (parieto-occipital and central). RESULTS: After carrying out post
      hoc multiple comparisons, for both electrode configurations we found significant
      differences between mild Alzheimer's patients and healthy elderly on beta- and
      theta-energy (%) only for the rare alpha scenario. No differences were found for
      the dominant alpha scenario in any of the five frequency bands. CONCLUSIONS: This
      is the first study of Alzheimer's awake-EEG reporting the influence of alpha
      rhythm on epoch selection, where our results revealed that, contrarily to what
      was most likely expected, less synchronized EEG epochs (rare alpha scenario)
      better discriminated mild Alzheimer's than those presenting abundant alpha
      (dominant alpha scenario). In addition, we find out that epoch selection is a
      very sensitive issue in qEEG research. Consequently, for Alzheimer's studies
      dealing with resting state EEG, we propose that epoch selection strategies should
      always be cautiously designed and thoroughly explained.

PMID- 27886712
TI  - A SAS macro for the joint modeling of longitudinal outcomes and multiple
      competing risk dropouts.
AB  - BACKGROUND AND OBJECTIVES: The joint modeling of longitudinal and survival data
      to assess effects of multiple informative dropout mechanisms on longitudinal
      outcomes inference has received considerable attention during recent years;
      related statistical programs to apply these methods have been lacking. This paper
      provides a SAS macro implementation of a shared parameter model to accommodate
      the analysis of longitudinal outcomes in the presence of multiple competing
      survival/dropout events. METHODS: In this macro, we assumed that the associations
      between the survival and the longitudinal submodels are linked through a set of
      shared random effects. The submodel for the longitudinal outcome takes the form
      of a linear mixed effects model, with specifications for the random intercept
      and/or random slope. The survival submodel allows up to three different competing
      causes for dropout, each allowing either an exponential or Weibull parametric
      baseline hazard function. In addition, information criterion fit statistics AIC
      and BIC are provided to assist with parametric baseline hazard function
      selection. RESULTS: We illustrate the SAS Macro in a cognitive decline study
      sensitivity analysis using data from the Atherosclerosis Risk in Communities
      Neurocognitive Study (ARIC-NCS). In addition, we also conduct a simulation study
      to show that the joint model provides unbiased parameter estimates when
      informative dropout exists compared against separate model approach which assumes
      missing at random dropout mechanisms. CONCLUSIONS: We have presented a SAS macro
      to implement a shared parameter model for a longitudinal outcome and multiple
      cause-specific dropouts and made the macro code freely available for download.

PMID- 27886714
TI  - Classification of CT brain images based on deep learning networks.
AB  - While computerised tomography (CT) may have been the first imaging tool to study
      human brain, it has not yet been implemented into clinical decision making
      process for diagnosis of Alzheimer's disease (AD). On the other hand, with the
      nature of being prevalent, inexpensive and non-invasive, CT does present
      diagnostic features of AD to a great extent. This study explores the significance
      and impact on the application of the burgeoning deep learning techniques to the
      task of classification of CT brain images, in particular utilising convolutional
      neural network (CNN), aiming at providing supplementary information for the early
      diagnosis of Alzheimer's disease. Towards this end, three categories of CT images
      (N = 285) are clustered into three groups, which are AD, lesion (e.g. tumour) and
      normal ageing. In addition, considering the characteristics of this collection
      with larger thickness along the direction of depth (z) (~3-5 mm), an advanced CNN
      architecture is established integrating both 2D and 3D CNN networks. The fusion
      of the two CNN networks is subsequently coordinated based on the average of
      Softmax scores obtained from both networks consolidating 2D images along spatial
      axial directions and 3D segmented blocks respectively. As a result, the
      classification accuracy rates rendered by this elaborated CNN architecture are
      85.2%, 80% and 95.3% for classes of AD, lesion and normal respectively with an
      average of 87.6%. Additionally, this improved CNN network appears to outperform
      the others when in comparison with 2D version only of CNN network as well as a
      number of state of the art hand-crafted approaches. As a result, these approaches
      deliver accuracy rates in percentage of 86.3, 85.6 +/- 1.10, 86.3 +/- 1.04, 85.2
      +/- 1.60, 83.1 +/- 0.35 for 2D CNN, 2D SIFT, 2D KAZE, 3D SIFT and 3D KAZE
      respectively. The two major contributions of the paper constitute a new 3-D
      approach while applying deep learning technique to extract signature information
      rooted in both 2D slices and 3D blocks of CT images and an elaborated hand-crated
      approach of 3D KAZE.

PMID- 27886713
TI  - Automated classification of Pap smear images to detect cervical dysplasia.
AB  - BACKGROUND AND OBJECTIVES: The present study proposes an intelligent system for
      automatic categorization of Pap smear images to detect cervical dysplasia, which
      has been an open problem ongoing for last five decades. METHODS: The
      classification technique is based on shape, texture and color features. It
      classifies the cervical dysplasia into two-level (normal and abnormal) and three
      level (Negative for Intraepithelial Lesion or Malignancy, Low-grade Squamous
      Intraepithelial Lesion and High-grade Squamous Intraepithelial Lesion) classes
      reflecting the established Bethesda system of classification used for diagnosis
      of cancerous or precancerous lesion of cervix. The system is evaluated on two
      generated databases obtained from two diagnostic centers, one containing 1610
      single cervical cells and the other 1320 complete smear level images. The main
      objective of this database generation is to categorize the images according to
      the Bethesda system of classification both of which require lots of training and
      expertise. The system is also trained and tested on the benchmark Herlev
      University database which is publicly available. In this contribution a new
      segmentation technique has also been proposed for extracting shape features.
      Ripplet Type I transform, Histogram first order statistics and Gray Level Co
      occurrence Matrix have been used for color and texture features respectively. To
      improve classification results, ensemble method is used, which integrates the
      decision of three classifiers. Assessments are performed using 5 fold cross
      validation. RESULTS: Extended experiments reveal that the proposed system can
      successfully classify Pap smear images performing significantly better when
      compared with other existing methods. CONCLUSION: This type of automated cancer
      classifier will be of particular help in early detection of cancer.

PMID- 27886715
TI  - A software program to measure the three-dimensional length of the spine from
      radiographic images: Validation and reliability assessment for adolescent
      idiopathic scoliosis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to validate a new program
      which aims at measuring the three-dimensional length of the spine's midline based
      on two calibrated orthogonal radiographic images. The traditional uniplanar T1-S1
      measurement method is not reflecting the actual three dimensional curvature of a
      scoliotic spine and is therefore not accurate. The Spinal Measurement Software
      (SMS) is an alternative to conveniently measure the true spine's length. METHODS:
      The validity, inter- and intra-observer variability and usability of the program
      were evaluated. The usability was quantified based on a subjective questionnaire
      filled by eight participants using the program for the first time. The validity
      and variability were assessed by comparing the length of five phantom spines
      measured based on CT-scan data and on radiographic images with the SMS. The
      lengths were measured independently by each participant using both techniques.
      RESULTS: The SMS is easy and intuitive to use, even for non-clinicians. The SMS
      measured spinal length with an error below 2 millimeters compared to length
      obtained using CT scan datasets. The inter- and intra-observer variability of the
      SMS measurements was below 5 millimeters. CONCLUSIONS: The SMS provides accurate
      measurement of the spinal length based on orthogonal radiographic images. The
      software is easy to use and could easily integrate the clinical workflow and
      replace current approximations of the spinal length based on a single
      radiographic image such as the traditional T1-S1 measurement.

PMID- 27886716
TI  - Simulating the dynamics of lipid droplets in adipocyte differentiation.
AB  - BACKGROUND: Lipid droplets are cellular organelles that regulate the storage and
      hydrolysis of neutral lipids. The dynamic of lipid droplets (LDs), during the
      differentiation process from fibroblast-like cells into adipocyte, is strictly
      related to the lipid storage in cells. The number and size of the LDs depends on
      the lipidic or lipolytic stimulations to which the cells are exposed. METHOD:
      Here, we propose a computational approach to study the processes regulating the
      LDs' number and growth/reduction in size using Monte Carlo simulations. The
      number and size of LDs are measured before and after experimental treatment in
      3T3-L1 cell cultures. The algorithms simulating the evolution from basal to
      differentiate (lipidic or lipolytic) conditions are here detailed step by step.
      The algorithms can mimic thousand interacting events between LDs or
      squeezing/enlargement events of a single LD in a very brief computational time,
      from seconds up to few minutes. RESULTS: The main processes regulating the
      interactions between LDs are here presented, and for each of them, all the needed
      information to re-write the computational routine are provided. More
      specifically, the results obtained, analyzing the fusion process between LDs, are
      here presented. CONCLUSIONS: Here, we would like to supply the basis to explore
      the dynamics of lipid storage in cells with a computational approach and to
      encourage the applications of numerical simulation to cell studies.

PMID- 27886717
TI  - RUbioSeq+: A multiplatform application that executes parallelized pipelines to
      analyse next-generation sequencing data.
AB  - BACKGROUND AND OBJECTIVE: To facilitate routine analysis and to improve the
      reproducibility of the results, next-generation sequencing (NGS) analysis
      requires intuitive, efficient and integrated data processing pipelines. METHODS:
      We have selected well-established software to construct a suite of automated and
      parallelized workflows to analyse NGS data for DNA-seq (single-nucleotide
      variants (SNVs) and indels), CNA-seq, bisulfite-seq and ChIP-seq experiments.
      RESULTS: Here, we present RUbioSeq+, an updated and extended version of RUbioSeq,
      a multiplatform application that incorporates a suite of automated and
      parallelized workflows to analyse NGS data. This new version includes: (i) an
      interactive graphical user interface (GUI) that facilitates its use by both
      biomedical researchers and bioinformaticians, (ii) a new pipeline for ChIP-seq
      experiments, (iii) pair-wise comparisons (case-control analyses) for DNA-seq
      experiments, (iv) and improvements in the parallelized and multithreaded
      execution options. Results generated by our software have been experimentally
      validated and accepted for publication. CONCLUSIONS: RUbioSeq+ is free and open
      to all users at http://rubioseq.bioinfo.cnio.es/.

PMID- 27886718
TI  - Detecting retinal microaneurysms and hemorrhages with robustness to the presence
      of blood vessels.
AB  - BACKGROUND AND OBJECTIVES: Diabetic Retinopathy is the leading cause of blindness
      in developed countries in the age group 20-74 years. It is characterized by
      lesions on the retina and this paper focuses on detecting two of these lesions,
      Microaneurysms and Hemorrhages, which are also known as red lesions. This paper
      attempts to deal with two problems in detecting red lesions from retinal fundus
      images: (1) false detections on blood vessels; and (2) different size of red
      lesions. METHODS: To deal with false detections on blood vessels, novel filters
      have been proposed which can distinguish between red lesions and blood vessels.
      This distinction is based on the fact that vessels are elongated while red
      lesions are usually circular blob-like structures. The second problem of the
      different size of lesions is dealt with by applying the proposed filters on
      patches of different sizes instead of filtering the full image. These patches are
      obtained by dividing the original image using a grid whose size determines the
      patch size. Different grid sizes were used and lesion detection results for these
      grid sizes were combined using Multiple Kernel Learning. RESULTS: Experiments on
      a dataset of 143 images showed that proposed filters detected Microaneurysms and
      Hemorrhages successfully even when these lesions were close to blood vessels. In
      addition, using Multiple Kernel Learning improved the results when compared to
      using a grid of one size only. The areas under receiver operating characteristic
      curve were found to be 0.97 and 0.92 for Microaneurysms and Hemorrhages
      respectively which are better than the existing related works. CONCLUSIONS:
      Proposed filters are robust to the presence of blood vessels and surpass related
      works in detecting red lesions from retinal fundus images. Improved lesion
      detection using the proposed approach can help in automatic detection of Diabetic
      Retinopathy.

PMID- 27886719
TI  - A dual stage adaptive thresholding (DuSAT) for automatic mass detection in
      mammograms.
AB  - BACKGROUND AND OBJECTIVE: Early detection and diagnosis of breast cancer through
      mammography screening reduces breast cancer mortality by around 20%. However it
      is often a complex process to differentiate abnormalities due to the ill-defined
      margins and subtle appearances. METHOD: This paper investigates a new computer
      aided approach to detect the abnormalities in the digital mammograms using a Dual
      Stage Adaptive Thresholding (DuSAT). The suspicious mass region is identified
      using global histogram and local window thresholding method. The global
      thresholding is done based on the Histogram Peak Analysis (HPA) of the entire
      image and the threshold is obtained by maximizing the proposed threshold
      selection criteria. The local thresholding is carried out for each pixel in a
      defined neighborhood window that provides precise segmentation results. RESULTS:
      The algorithm is verified with 300 images in the DDSM database and 170 images in
      the mini-MIAS database. Experimental results show that the proposed algorithm
      achieves an average sensitivity of 92.5% with 1.06 FP/image for DDSM database and
      an average sensitivity of 93.5% with 0.62 FP/image for mini-MIAS database.
      CONCLUSION: The achieved results depict that the proposed approach provides
      better results compared to other state-of-art methods for mass detection that
      helps the radiologists in diagnosis of breast cancer at early stage.

PMID- 27886720
TI  - Editorial.

PMID- 27886721
TI  - Appointment of racial/ethnic minority directors: Ethnic matching or visibility
      threat?
AB  - The purpose of this study is to identify the industry and community-level
      compositional factors that influence the appointment of racial/ethnic minorities
      to corporate boards. We derived hypotheses from two theoretical perspectives:
      ethnic matching and visibility threat. Our analysis relied on data from seventy
      three Standard & Poor's 500 companies between 1980 and 2000. We find important
      differences between and among racial/ethnic groups in terms of the mechanisms
      that shape board appointments. Consistent with the ethnic matching perspective,
      we find that the representation of Black and Hispanic board directors is strongly
      predicted by the racial/ethnic composition of the industry's labor force.
      Contrary to the visibility threat perspective, however, we find that the
      appointment of Asian directors is strongly predicted by the ethnic composition of
      the community where the firm is located.

PMID- 27886722
TI  - Gender, race & the veteran wage gap.
AB  - This paper analyzes earnings outcomes of Iraq/Afghanistan-era veterans. We
      utilize the 2009-2013 American Community Survey and a worker-matching methodology
      to decompose wage differences between veteran and non-veteran workers. Among
      fully-employed, 25-40 year-olds, veteran workers make 3% less than non-veteran
      workers. While male veterans make 9% less than non-veterans, female and black
      veterans experience a wage premium (2% and 7% respectively). Decomposition of the
      earnings gap identifies some of its sources. Relatively higher rates of
      disability and lower rates of educational attainment serve to increase the
      overall wage penalty against veterans. However, veterans work less in low-paying
      occupations than non-veterans, serving to reduce the wage penalty. Finally, among
      male and white subgroups, non-veterans earn more in the top quintile due largely
      to having higher educational attainment and greater representation in higher
      paying occupations, such as management.

PMID- 27886723
TI  - Accounting for structural and exchange mobility in models of status attainment:
      Social fluidity in five European countries.
AB  - This paper proposes a new method to distinguish structural from exchange mobility
      in status attainment models with interval endogenous variables. In order to
      measure structural mobility, the paper proposes to trace occupational and
      educational changes across generations using information provided by children
      about their fathers. The validity of the method is assessed by comparing the
      effects of father's socio-economic status and education on son's status and
      educational attainments, net of occupational upgrading and educational expansion,
      in five European countries: Britain, Denmark, Germany, Norway, and Spain, using
      data from the 2005 EU-SILC survey. The results show that the effect of father's
      on son's ISEI weakens greatly in all countries after considering occupational
      upgrading, and that much of father's influence over sons occurs by directing them
      towards occupations with good economic prospects. Useful extensions to the method
      are discussed in the conclusions.

PMID- 27886724
TI  - Sexual orientation differences in attitudes about sexuality, race, and gender.
AB  - Researchers have extensively documented sociodemographic predictors of race and
      gender attitudes, and the mechanisms through which such attitudes are formed and
      change. Despite its growing recognition as an important status characteristic,
      sexual orientation has received little attention as a predictor of Americans'
      race and gender attitudes. Using nationally representative data from the American
      National Election Survey 2012 Time Series Study, I compare heterosexuals' and
      lesbian, gay, and bisexual (LGB) people's attitudes about sexuality, race, and
      gender. For most attitudes, LGB people hold significantly more liberal attitudes
      about sexuality, race, and gender than do heterosexuals, even upon controlling
      for other powerful sociodemographic determinants of social attitudes. However, a
      substantial proportion of these sexual orientation gaps in attitudes - especially
      about race and gender - are explained by LGB people's relatively liberal
      political ideology. The findings provide evidence for the necessity of
      incorporating sexual orientation in future assessments of Americans' social and
      political attitudes.

PMID- 27886725
TI  - When love meets hate: The relationship between state policies on gay and lesbian
      rights and hate crime incidence.
AB  - Do public policies on gay and lesbian rights affect the incidence of hate crimes
      based on sexual orientation? We propose that legal inequalities increase hate
      crimes because they provide discursive opportunities for bias, discrimination,
      and violence. Legal equality, however, will reduce violence. Using annual panel
      data from 2000 to 2012, a period of substantial policy change, we analyze how
      three state policies affect reported hate crimes: same-sex partnerships,
      employment non-discrimination, and hate crime laws. Hate crime and employment non
      discrimination laws that include sexual orientation reduce hate crime incidence.
      Partnership recognition increases reported hate crimes, though it may not
      increase actual crime incidence. Because incidence is spatially correlated,
      policy changes in one state yield spillover benefits in other states. These
      results provide some of the first quantitative evidence that public policies
      affect hate crimes based on sexual orientation. Findings confirm the roles of
      institutional heterosexism and discursive opportunities in producing hate crimes.

PMID- 27886726
TI  - What fosters concern for inequality among American adolescents?
AB  - Understanding cultural beliefs about social and economic inequality is vital to
      discerning the roadblocks and pathways to addressing that inequality. The
      foundation of concern for inequality is laid during adolescence, yet scholars
      understand little about the factors that influence whether and how adolescents
      come to express such concern. Arguing that structural and cultural contexts are
      just as consequential as whether adolescents themselves are members of
      disadvantaged groups, I draw on four theoretical perspectives to identify factors
      that influence adolescents' concern for addressing inequality: the underdog
      thesis, intergroup contact theory, the education enlightens thesis, and
      ideological buttressing. Using representative restricted-use Educational
      Longitudinal Survey data, I find that 12th-graders' beliefs are indeed influenced
      by more than their own demography: the diversity of their social milieu, the
      content of education in and out of the classroom, and ideological buttressing via
      political region and entertainment all influence whether they express concern for
      addressing inequality. These findings suggest extensions and amendments to the
      four theoretical perspectives and underscore the importance of studying
      structural and cultural factors that shape beliefs about inequality. The results
      also point to several interventions that may increase students' concern for
      inequality: involvement in civic-oriented extracurricular activities, more
      education in academic subjects that consider inequality, nurturing of cross-race
      friendships, and increased leisure reading.

PMID- 27886727
TI  - You can't always get what you want: Network determinants of relationship
      inactualization in adolescence.
AB  - Despite widespread interest in the link between social and sexual networks,
      little research has focused on how social networks influence the progression of
      intimate relationships (e.g., from holding hands to sexual intercourse). I argue
      that social networks not only affect individuals' opportunities to meet romantic
      partners, but also shape the ideal and actual progressions of intimate acts
      within their relationships. Using data from the National Longitudinal Survey of
      Adolescent to Adult Health (Add Health), I conduct an optimal matching analysis
      of adolescents' purported ideal versus actual relationship sequences, which are
      comprised of romantic and sexual events. Low discrepancy scores indicate that
      intimate acts in one's recent relationship were sequenced much as one had
      desired. Results demonstrate that how students are situated within their schools'
      broader friendship networks affects their experiences with intimacy: high rank
      prestige individuals are better able to achieve their ideal relationships, as are
      individuals with densely knit friendship networks. Additionally, increased gender
      salience among boys within the socio-centric friendship network is associated
      with increased discord between desired and actual relationship progressions, but
      this relationship is mediated by the rareness of the individual's ideal
      relationship trajectory.

PMID- 27886728
TI  - Do legal school leaving rules still affect schooling and earnings?
AB  - This paper quantifies whether compulsory schooling laws are still effective in
      the 21st century and if so, to what extent the school compulsion continues to
      influence individuals' educational achievement and labor market earnings. Using
      American Community Survey, I find that compulsory schooling laws were effective
      for the white men and women born in the 1930s and 1940s in the U.S.; however,
      they no longer produce the same seasonality effects on the educational attainment
      of the white cohorts who completed their educational attainment in the 2000s. I
      also find that the school compulsion was not binding for the older African
      American cohorts; however, they were effective in keeping the younger African
      American men at school longer.

PMID- 27886729
TI  - Reducing children's behavior problems through social capital: A causal
      assessment.
AB  - Behavior problems among young children have serious detrimental effects on short
      and long-term educational outcomes. An especially promising prevention strategy
      may be one that focuses on strengthening the relationships among families in
      schools, or social capital. However, empirical research on social capital has
      been constrained by conceptual and causal ambiguity. This study attempts to
      construct a more focused conceptualization of social capital and aims to
      determine the causal effects of social capital on children's behavior. Using data
      from a cluster randomized trial of 52 elementary schools, we apply several
      multilevel models to assess the causal relationship, including intent to treat
      and treatment on the treated analyses. Taken together, these analyses provide
      stronger evidence than previous studies that social capital improves children's
      behavioral outcomes and that these improvements are not simply a result of
      selection into social relations but result from the social relations themselves.

PMID- 27886730
TI  - School transitions, peer influence, and educational expectation formation: Girls
      and boys.
AB  - School transitions are a regular feature of the educational career. While they
      are of general interest as instances of academic change, they also represent
      instances of peer environment and influence change. Previous theoretical and
      empirical work suggests peer influence is important for students' academic and
      educational outcomes, especially for the complex decision-making processes
      leading up to those outcomes. In this manuscript, we study the impact of peers on
      educational expectation formation at the 8th-to-9th-grade school transition. In
      doing so, we test a theoretical model that links institutional settings, social
      influence, and individual decision-making. We find the 9th grade transition
      likely represents a negative shock for students' college attendance expectations.
      Independent of this transition, however, stable peer environments further depress
      expectations. A more equal mixture of new and old peers in the 9th grade likely
      increases students' educational expectations in contrast. These effects of peer
      perturbations and the re-organization of social ties they imply mainly apply to
      female students. But, both male and female students revise their educational
      expectations in light of changing peer intelligence comparisons, albeit in
      countervailing ways.

PMID- 27886731
TI  - Social capital, friendship networks, and youth unemployment.
AB  - Youth unemployment is a contemporary social problem in many societies. Youths
      often have limited access to information about jobs and limited social influence,
      yet little is known about the relationship between social capital and
      unemployment risk among youth. We study the effect of social capital on
      unemployment risk in a sample of 19 year olds of Swedish, Iranian, and
      Yugoslavian origin living in Sweden (N = 1590). We distinguish between two
      dimensions of social capital: occupational contact networks and friendship
      networks. First, ego's unemployment is found to be strongly associated with
      friends' unemployment among individuals of Yugoslavian origins and individuals of
      Swedish origin, but not Iranian origin. Second, occupational contact networks
      reduce unemployment risks for all groups, but especially so for Iranians. The
      effect sizes of the two dimensions are similar and substantial: going from low to
      high values on these measures is associated with a difference of some 60-70
      percent relative difference in unemployment risk. The findings are robust to a
      number of different model specifications, including a rich set of social origin
      controls, personality traits, educational performance, friends' characteristics,
      and friendship network characteristics, as well as controls for geographical
      employment patterns. A sensitivity simulation shows that homogeneity bias need to
      be very strong to explain away the effect.

PMID- 27886733
TI  - Maternal social status, early health capital, and young adults' economic
      attainment: Early life course investigation.
AB  - Using survey data collected from 12,278 adolescents and their mothers over 13
      years in a nationally representative National Longitudinal Study of Adolescent
      Health, this study examined how maternal social status influenced young adults'
      economic attainment over the early life course. We found that weight at birth and
      height at adolescence as early health capital mediated the influence of maternal
      social status on young adults' economic attainment. Also, adolescents'
      educational attainment and psychological vulnerabilities mediated the relation
      between early health capital and young adults' economic attainment. These
      findings highlight the importance of early intervention to prevent the persistent
      influence of adverse maternal social status on youths' developmental outcomes.

PMID- 27886734
TI  - Does the internet affect assortative mating? Evidence from the U.S. and Germany.
AB  - The Internet has now become a habitual channel for finding a partner, but little
      is known about the impact of this recent partnership market on mate selection
      patterns. This study revisits the supply side perspective on assortative mating
      by exploring the role played by online venues in breeding educational,
      racial/ethnic and religious endogamy. It compares couples that met online
      (through either online dating platforms, Internet social networking, Internet
      gaming website, Internet chat, Internet community, etc.) to those that met
      through various offline contexts of interaction. Using unique data from the U.S.
      for the year 2009 and data from Germany collected between 2008 and 2014, I run
      log-multiplicative models that allow for the strength of partners' association to
      vary along meeting settings. Results reveal that the Internet promotes weaker
      couple endogamy compared to conventional contexts typically known to foster
      endogamy, such as school, family, friends, or religious venues.

PMID- 27886732
TI  - Attention-deficit/hyperactivity disorder severity, diagnosis, & later academic
      achievement in a national sample.
AB  - Although 11% (6.4 million) American children are diagnosed with attention
      deficit/hyperactivity disorder (ADHD), the role of ADHD severity in shaping the
      association between ADHD diagnosis and academic achievement is not understood.
      Using a nationally-representative sample of 7830 U.S. kindergartners from the
      Early Childhood Longitudinal Study-Kindergarten Cohort, we use regression and
      propensity score matching to compare diagnosed (N = 350) and undiagnosed children
      who are cognitively, behaviorally, and demographically similar. Diagnosed
      children with less severe ADHD-related behaviors on average scored lower in
      reading (-0.30 SD) and math (-0.22 SD) than their undiagnosed peers - a
      difference two times larger than that between diagnosed and undiagnosed children
      with more severe ADHD-related behaviors. Pharmacological treatment did not
      attenuate most of this "diagnostic labeling effect" among children with less
      severe ADHD-related behaviors. Negative factors associated with an ADHD diagnosis
      may outweigh potential benefits for achievement among children with less severe
      ADHD-related behaviors, even those receiving treatment.

PMID- 27886736
TI  - Pushed or pulled? Girls and boys facing early school leaving risk in Italy.
AB  - Compared to girls, boys are more at risk of early school leaving. However, it is
      unclear whether gender differences are driven by push factors, which alienate
      students from the school system, or pull factors, which attract them out of it.
      This paper examines gender differences in early school leaving, assessing the
      role of previous scholastic performance, parental education, and differential
      employment opportunities. By analyzing two nationally representative datasets, we
      focus on Italy, a country with high rates of early school leaving and pronounced
      gender inequalities in the labor market. Our results show that gender effects are
      partially mediated by scholastic performance, a crucial push factor, and are
      stronger among low-achieving students, pointing to a higher resilience of girls
      to academic failure; parental education is highly protective, especially for
      boys. Yet, boys' higher propensity to drop out is also, at least partly,
      explained by better employment opportunities in the formal and informal labor
      market.

PMID- 27886735
TI  - Residential segregation and racial disparities in self-rated health: How do
      dimensions of residential segregation matter?
AB  - Previous research on segregation and health has been criticized for overlooking
      the fact that segregation is a multi-dimensional concept (i.e., evenness,
      exposure, concentration, centralization, and clustering) and recent evidence
      drawn from non-black minorities challenges the conventional belief that
      residential segregation widens racial health disparities. Combining a survey data
      (n = 18,752) from Philadelphia with the 2010 Census tract (n = 925) data, we
      examine two theoretical frameworks to understand why the association of
      segregation with health may differ by race/ethnicity. Specifically, we
      investigate how each dimension of segregation contributed to racial disparities
      in self-rated health. We found (1) high levels of white/black concentration could
      exacerbate the white/black health disparities up to 25 percent, (2) the
      white/Hispanic health disparities was narrowed by increasing the level of
      white/Hispanic centralization, and (3) no single dimension of segregation
      statistically outperforms others. Our findings supported that segregation is bad
      for blacks but may be beneficial for Hispanics.

PMID- 27886738
TI  - Political economy of family life: couple's earnings, welfare regime and union
      dissolution.
AB  - This study examines how institutional settings moderate the relation of couples'
      relative and absolute earnings to the likelihood of union dissolution. Based on
      ECHP data, it covers 12 countries in four welfare regimes. The relationship
      between a couple's economic dependence and the likelihood of union dissolution
      were found to differ across regimes. With regard to relative earnings, equality
      in earnings lowered the risk of separation only in regimes characterized by a
      high degree of defamilialization, through either the state or the market. As for
      absolute earnings, women's and men's earnings were significantly related to the
      risk of union dissolution only in regimes where state defamilialization is low.

PMID- 27886737
TI  - Social context of first birth timing in a rapidly changing rural setting.
AB  - This article examines the influence of social context on the rate of first birth.
      Drawing on socialization models, I develop a theoretical framework to explain how
      different aspects of social context (i.e., neighbors), may affect the rate of
      first birth. Neighbors, who in the study setting comprise individuals' immediate
      social context, have an important influence on the rate of first birth. To test
      my hypotheses, I leverage a setting, measures and analytical techniques designed
      to study the impact of macro-level social contexts on micro-level individual
      behavior. The results show that neighbors' age at first birth, travel to the
      capital city and media exposure tend to reduce the first birth rate, while
      neighbors' non-family work experience increases first birth rate. These effects
      are independent of neighborhood characteristics and are robust against several
      key variations in model specifications.

PMID- 27886739
TI  - Occupational segregation and earnings inequality: Rural migrants and local
      workers in urban China.
AB  - This article examines the central role of occupation as the "reward packages" in
      creating earnings disparities between rural migrants and local workers in urban
      China's labor markets. Analyses of data from the population mini-census of China
      in 2005 show that, rural migrants' earnings disadvantages are largely
      attributable to occupational segregation (between-occupation variation) by
      workers' household registration status (hukou) rather than unequal pay within the
      same occupations, but surprisingly they enjoy a slight earnings advantage in
      lower-status occupations (within-occupation variation). Even after controlling
      for education and other characteristics, occupational segregation by hukou status
      continues to exist. The occupational segregation is the most severe in government
      agencies/state institutions and the least severe in the private sector, leading
      to earnings disparities between rural migrants and urban local workers in
      different work unit sectors. Our findings shed new light on how government
      discriminatory policies could affect occupational segregation and thereby create
      inequality among social groups in urban China.

PMID- 27886740
TI  - Local peace and contemporary conflict: Constructing commonality and exclusion
      during war in Afghanistan.
AB  - Despite the "local turn" in international peacekeeping and the emphasis on
      community-centered development during the recent wars in Afghanistan and Iraq, it
      remains poorly understood how local actors-both foreign and indigenous-shape
      local-level wartime settings. This article explores the processes and
      consequences of one military unit's efforts to "win hearts and minds" in
      Afghanistan during 2012-13. The first portion of the analysis examines original
      textual data with a novel methodological approach depicting the unit's
      perceptions of commonalities between itself and local actors. The second portion
      explores the consequences with data from original interviews with residents of
      southern Afghanistan in 2014-15. The findings suggest that achieving a local
      peace can be undermined by military and development actors' own perception of the
      local community. The article concludes with a discussion of how sociological
      studies of micro-settings between actors can contribute to research on conflict
      and wartime development, as well as how the sociological study of war can further
      develop by disaggregating conflict settings and tracing the social construction
      of wartime socio-political landscapes.

PMID- 27886741
TI  - Spread of status value: Rewards and the creation of status characteristics.
AB  - Rewards have social significance and are highly esteemed objects, but what does
      their ownership signify to others? Prior work has demonstrated it may be possible
      for these rewards to spread their status to those who possess them, such that
      individuals gain or lose status and influence by virtue of the rewards they
      display. Yet, is this spread enough to produce entirely new status
      characteristics by virtue of their association with rewards? I propose a
      theoretical extension of the spread of status value theory and offer an
      experimental test considering whether the status value conveyed by rewards
      spreads to a new, nominal characteristic of those who come to possess these
      objects. The results indicate that states of a nominal characteristic do gain or
      lose status value and behavioral influence through their association with
      differentially valued rewards. Thus, rewards can create new status
      characteristics with resulting behavioral expectations.

PMID- 27886742
TI  - Drugs for chronic diseases: getting the price right.

PMID- 27886743
TI  - Misrepresented risk of thyroid cancer in Fukushima.

PMID- 27886744
TI  - Misrepresented risk of thyroid cancer in Fukushima - Authors' reply.

PMID- 27886745
TI  - Are statins useful in patients with advanced chronic kidney disease?

PMID- 27886746
TI  - Are statins useful in patients with advanced chronic kidney disease? - Authors'
      reply.

PMID- 27886747
TI  - Primary aldosteronism as a public health issue.

PMID- 27886748
TI  - Primary aldosteronism as a public health issue - Authors' reply.

PMID- 27886749
TI  - Papillary thyroid microcarcinoma and active surveillance.

PMID- 27886750
TI  - Papillary thyroid microcarcinoma and active surveillance.

PMID- 27886751
TI  - Papillary thyroid microcarcinoma and active surveillance.

PMID- 27886752
TI  - Papillary thyroid microcarcinoma and active surveillance.

PMID- 27886753
TI  - Papillary thyroid microcarcinoma and active surveillance - Authors' reply.

PMID- 27886754
TI  - Chernobyl: assessing the health effects, 30 years later.

PMID- 27886755
TI  - Correction to Lancet Diabetes Endocrinol 2016; 4: 885-86.

PMID- 27886756
TI  - Correction to Lancet Diabetes Endocrinol 2016; 4: 960-61.

PMID- 27886757
TI  - Different sample treatments for the determination of ICM-XR in fish samples
      followed by LC-HRMS.
AB  - Iodinated X-ray contrast media (ICM-XR) are a group of pharmaceuticals widely
      used in medicine. Due to their low biodegradation rate, which makes their removal
      at wastewater treatment plants difficult, and the high doses at which they are
      administered, they have been detected in aquatic environments. In the present
      paper, a method for the quantitative determination of a group of ICM-XR in
      different fish species was developed and validated for the first time. Two
      extraction techniques were compared: pressurised liquid extraction (PLE) and
      QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe), with PLE being
      selected, followed by liquid chromatography-high resolution mass spectrometry. In
      addition, several clean-up strategies were evaluated. The optimised method
      provided PLE recoveries ranging from 60% to 88% and limits of detection ranging
      from 5ng/g to 25ng/g (dry weight). The method was applied in order to evaluate
      the presence of the selected ICM-XR in different fish species.

PMID- 27886758
TI  - Sensing tyrosine enantiomers by using chiral CdSe/CdS quantum dots capped with N
      acetyl-l-cysteine.
AB  - Despite of the importance of enantiomers, the fluorescence sensing of enantiomers
      and the interpretation of the "preferential interaction" still remain
      insufficiently explored. In this study, we report the recognition of tyrosine
      (Tyr) enantiomers by chiral N-acetyl-L-cysteine (L-NAC) capped CdSe/CdS quantum
      dots (QDs) under alkaline experimental condition. L-Tyr could greatly quench the
      fluorescence of CdSe/CdS QDs, while D-Tyr displayed no effect on the
      fluorescence. The one-step synthesized chiral L-NAC-CdSe/CdS QDs demonstrated
      high selectivity for Tyr enantiomers. In particular, the mechanism of chiral
      recognition has been studied by UV/vis absorption spectra and circular dichroism
      (CD) spectra. The changes of intensity and sign of CD spectra corroborated the
      attachment of L-Tyr to the surface of QDs, which may be valuable aids in
      obtaining a better understanding of the possible mechanism of enantioselective
      recognition.

PMID- 27886760
TI  - Practical limitations of single particle ICP-MS in the determination of
      nanoparticle size distributions and dissolution: case of rare earth oxides.
AB  - The applicability of single particle ICP-MS (SP-ICP-MS) for the analysis of
      nanoparticle size distributions and the determination of particle numbers was
      evaluated using the rare earth oxide, La2O3, as a model particle. The composition
      of the storage containers, as well as the ICP-MS sample introduction system were
      found to significantly impact SP-ICP-MS analysis. While La2O3 nanoparticles
      (La2O3 NP) did not appear to interact strongly with sample containers, adsorptive
      losses of La3+(over 24h) were substantial (>72%) for fluorinated ethylene
      propylene bottles as opposed to polypropylene (<10%). Furthermore, each part of
      the sample introduction system (nebulizers made of perfluoroalkoxy alkane (PFA)
      or glass, PFA capillary tubing, and polyvinyl chloride (PVC) peristaltic pump
      tubing) contributed to La3+ adsorptive losses. On the other hand, the presence of
      natural organic matter in the nanoparticle suspensions led to a decreased
      adsorptive loss in both the sample containers and the introduction system,
      suggesting that SP-ICP-MS may nonetheless be appropriate for NP analysis in
      environmental matrices. Coupling of an ion-exchange resin to the SP-ICP-MS led to
      more accurate determinations of the La2O3 NP size distributions.

PMID- 27886759
TI  - Capillary electrophoresis-tandem mass spectrometry combined with molecularly
      imprinted solid phase extraction as useful tool for the monitoring of 5
      nitroimidazoles and their metabolites in urine samples.
AB  - A novel capillary electrophoresis-tandem mass spectrometry approach is proposed
      for the determination of eleven 5-nitroimidazoles in urine samples for
      therapeutical drug monitoring purposes. A comparison between two separation
      modes, namely micellar electrokinetic chromatography and capillary zone
      electrophoresis was carried out, obtaining higher selectivity when 1M formic acid
      (pH 1.8) was selected as background electrolyte. 5-Nitroimidazoles were
      hydrodynamically injected in water for 40s at 50mbar and their separation was
      performed at 28kV and 25 degrees C. To improve migration time repeatability, a
      pressure of 50mbar was applied to the inlet vial during runs without any loss of
      peak resolution. Electrospray ionization parameters were established as follow:
      6L/min, dry gas flow rate; 51,021.2Pa, nebulization pressure; 160 degrees C, dry
      gas temperature. Sheath liquid consisted of a mixture of propan-2-ol/water/acetic
      acid (60.0:38.8:0.2% v/v/v) supplied at 3.3uL/min. MS parameters were optimized
      for analyte identification through their MS2 and MS3 spectra. The method was
      applied to the determination of 5-nitroimidazoles in urine samples, applying
      molecularly imprinted solid phase extraction for sample clean-up. Recoveries
      higher than 79.2% demonstrated the suitability of the procedure. Limits of
      detection ranged from 9.6 to 130.2ug/L while precision assays resulted in
      relative standard deviations for peak areas lower than 16.1%.

PMID- 27886761
TI  - Simultaneous determination of La, Ce, Pr, and Nd elements in aqueous solution
      using surface-enhanced laser-induced breakdown spectroscopy.
AB  - Determination of rare earth elements (REEs) plays an important role in the
      extraction process. In this work, surface-enhanced laser-induced breakdown
      spectroscopy (SENLIBS) was introduced to detect REEs (lanthanum,
      cerium,praseodymium,and neodymium elements) in an aqueous solution. The emission
      lines of La II 394.91nm, Ce II 418.66nm, Pr II 422.29nm, and Nd II 406.10nm were
      selected for quantitative analysis by drying the analytical samples on a Zn metal
      substrate surface and optimizing the experimental parameters. The results showed
      that the limits of detection (LoDs) for determining La, Ce, Pr, and Nd elements
      can reach to 0.85, 4.07, 2.97, and 10.98MUgmL-1, respectively, which proved that
      SENLIBS is a feasible method for determining REEs.

PMID- 27886763
TI  - DNA covalently linked to graphene oxide for biotin-streptavidin interaction
      assay.
AB  - Based on terminal protection of small molecule-linked DNA and the covalently
      linking DNA to graphene oxide (GO) strategy, a high resisting nonspecific probe
      displacement platform for small molecule-protein interaction assay is proposed in
      this work. Specifically, the small molecule-linked DNA (probe 1) can be protected
      from exonuclease-catalyzed digestion upon binding to the protein target of the
      small molecule, so the DNA strand may hybridize with another DNA strand (FAM and
      amino dual modified DNA, probe 2) that is previously covalently linked onto GO
      surface. Such hybridization will result in the fluorescence restoration of FAM.
      Taking biotin-streptavidin (SA) interaction assay as an example in this work, the
      linearity, stability and specificity of the covalent sensor were systematically
      studied and compared to the noncovalent sensor. The covalent sensor can determine
      the protein in a linear range from 0.15 to 12nM with a detection limit of 0.08nM,
      which is comparable with that of noncovalent sensor. Though both sensors have
      similar sensitivity, the covalent one is more resistant to nonspecific probe
      displacement by proteins. Furthermore, because the covalent sensor can be used
      for the assay of biotin-SA interaction in serum samples, this novel method is
      expected to have great potential applications in the future.

PMID- 27886762
TI  - Core-shell Cu@Au nanoparticles-based colorimetric aptasensor for the
      determination of lysozyme.
AB  - A growing body of evidence indicates that lysozyme plays a significant role as an
      indicator for many diseases and a drug for treatment of infections, ulcers and to
      study the spatial conformation, enzyme kinetics, and molecular immunology.
      Therefore, highly sensitive determination of lysozyme is necessary and vital in a
      wide variety of fields. In this work, we put forward a simple but effective
      strategy for colorimetric visualization of lysozyme based on iodide-responsive
      Cu@Au nanoparticles (Cu@Au NPs) as well as the iodide-catalyzed H2O2-TMB (3,3,5,5
      tetramethylbenzidine) reaction system. Colorimetric detection is applied because
      of its simplicity, fast response for analysis, high detection limit, low costs
      and practicality. In our strategy, iodide is applied for the reason that it can
      induce an obvious color change of the Cu@Au nanoparticles solution from gray to
      red, along with the change of morphologies of the Cu@Au nanoparticles from
      irregular to spherical. Consequently, this phenomenon results in colorimetric
      signal variation of the iodide-catalytic H2O2-TMB system. What's more, by quite
      simple biomolecule modification on the Cu@Au nanoparticles surface, an all
      purpose colorimetric platform is established for the accurate detection of
      lysozyme, which could lead to the change of Cu@Au NP concentration through
      molecular recognition. The results show that modified Cu-Au NPs successfully
      achieved a simple, selective, visualized, and ultrasensitive detection of
      lysozyme with a linear range from 10-7 to 10-3M and a detection limit of 60nM.

PMID- 27886764
TI  - Sensitive and selective colorimetric assay of alkaline phosphatase activity with
      Cu(II)-phenanthroline complex.
AB  - Alkaline phosphatase (ALP) plays a vital role in dephosphorylation- and
      phosphorylation-related cellular regulation and signaling processes. Accordingly,
      the development of efficient methods for ALP activity assay is of significant
      importance in clinical diagnosis. In this work, a simple and practical method is
      reported for the first time for the sensitive and selective colorimetric assay of
      ALP activity by exploiting a water-soluble Cu(II)-phenanthroline complex as the
      probe, on the basis of the distinctive metal-to-ligand charge-transfer (MLCT)
      properties. This method is simply built on a two-step chromogenic reaction: the
      enzymatic hydrolysis of the substrate ascorbic acid 2-phosphate to ascorbic acid
      (AA), followed by the reduction of the colorimetric probe Cu(BPDS)22-
      (BPDS=bathophenanthroline disulfonate) by AA to its cuprous form. The latter
      process triggers a turn-on spectral absorption at 424nm and a striking color
      change of the solution from colorless to blackish-green. Needless of complicated
      protocols and instrumentation, this method allows a sensitive readout of ALP
      activity within a wide linear range of 0-200mUmL-1, with a detection limit down
      to 1.25mUmL-1. Results also reveal that it is highly selective and holds great
      potential in ALP inhibitor efficiency evaluation. In addition, quantitative
      analysis of ALP activity in spiked serum samples has been realized successfully
      in the linear range of 0-200mUmL-1, with a detection limit of 1.75mUmL-1.
      Advantages of simplicity, wide linear range, high sensitivity and selectivity,
      low cost, and little background interference render this method great potential
      in practical applications.

PMID- 27886765
TI  - Analytical advantages of copolymeric microspheres for fluorimetric sensing -
      tuneable sensitivity sensors and titration agents.
AB  - Analytical benefits related to application of copolymeric microspheres containing
      different number of carboxylic acid mers have been studied on example of acrylate
      copolymers. These structures can be used as a reagent in heterogeneous pH
      titration, benefiting from different number of reactive groups - i.e. different
      concentration of a titrant - within the series of copolymers. Thus introducing
      the same amount of different microspheres from a series to the sample, different
      amount of the titrant is introduced. Copolymeric microspheres also can be used as
      optical sensors - in this respect the increasing number of reactive groups in the
      series is useful to improve the analytical performance of microprobes -
      sensitivity of determination or/and response range. The increase in ion
      permeability of the spheres with increasing number of reactive mers is
      advantageous. It is shown that for pH sensitive microspheres containing higher
      number of carboxyl groups the higher sensitivity for alkaline pH samples is
      observed for an indicator present in the beads. The significant increase of
      optical responses is related to enhanced ion transport within the microspheres.
      For zinc or potassium ions model sensors tested it was shown that by choice of pH
      conditions and type of microspheres from the series, the optical responses can be
      tuned - to enhance sensitivity for analyte concentration change as well as to
      change the response pattern from sigmoidal (higher sensitivity, narrow range) to
      linear (broader response range). For classical optode systems (e.g. microspheres
      containing an optical transducer - pH sensitive dye and optically silent
      ionophore - receptor) copolymeric microspheres containing carboxylic acid mers in
      their structure allow application of the sensor in alkaline pH range, which is
      usually inaccessible for applied optical transducer.

PMID- 27886766
TI  - Hydrothermal carbonaceous sphere based stationary phase for anion exchange
      chromatography.
AB  - Monodisperse carbonaceous spheres produced by the hydrothermal carbonization of
      sucrose were first applied as green stationary phase for ion chromatography after
      quaternization. Depending on the polycondensation of methylamine and 1,4
      butanediol diglycidyl ether, polymer containing quaternary ammonium groups were
      facilely grafted onto the surfaces of hydrothermal carbonaceous spheres (HCSs).
      The quaternized HCSs with different number of polyelectrolyte layers were
      characterized by scanning electron microscopy, brunauer-emmett-teller, fourier
      transform infrared spectroscopy, X-ray photoelectron spectroscopy,
      thermogravimetric analysis and elemental analysis. The measurements of
      breakthrough curves demonstrated that more layers of grafted polyelectrolyte
      resulted in higher anion exchange capacity of stationary phase. With good
      stability, common inorganic anions, monocarboxylic acids, polarizable anions and
      carbohydrates were effectively separated on the stationary phases, respectively.
      The high hydrophilicity of HCS surface afforded excellent peak symmetry for all
      analytes. Furthermore, high-capacity HCSs stationary phase was successfully
      applied to detect fluoride in tea samples.

PMID- 27886768
TI  - Three-point multivariate calibration models by correlation constrained MCR-ALS: A
      feasibility study for quantitative analysis of complex mixtures.
AB  - When it comes to address quantitative analysis in complex mixtures, Partial Least
      Squares (PLS) is often referred to as a standard first-order multivariate
      calibration method. The set of samples used to build the PLS regression model
      should ideally be large and representative to produce reliable predictions. In
      practice, however, the large number of calibration samples is not always
      affordable and the choice of these samples should be handled with care as it can
      significantly affect the accuracy of the predictive model. Correlation
      constrained multivariate curve resolution (CC-MCR) is an alternative regression
      method for first-order datasets where, unlike PLS, calibration and prediction
      stages are performed iteratively and optimized under constraints until the
      decomposition meets the convergence criterion. Both calibration and test samples
      are fitted into a unique bilinear model so that the number of calibration samples
      is no longer a critical issue. In this paper we demonstrate that under certain
      conditions CC-MCR models can provide for reasonable predictions in quantitative
      analysis of complex mixtures even when only three calibration samples are
      employed. The latter are defined as samples having the minimum, the maximum and
      the average concentration, providing for a simple and rapid strategy to build
      reliable calibration model. The feasibility of three-point multivariate
      calibration approach was assessed with several case studies featuring mixtures of
      different analytes in presence of interfering species. Satisfactory predictions
      with relative errors in the range 3-15% were achieved and good agreement with
      classical PLS models built from a larger set of calibration samples was observed.

PMID- 27886769
TI  - Polyethylene comonomer characterization by using FTIR and a multivariate
      classification technique.
AB  - Many polyethylene (PE) films used in various packaging applications are based on
      multi-layer systems and are fabricated by using the coextrusion techniques that
      can combine different raw materials. The identification of the comonomer type
      (octene - C8, hexene - C6 and butene - C4) in films, where two or more different
      linear low density polyethylene (LLDPE) resins are present, is becoming a
      frequent request. This report presents a novel approach where multivariate
      classification techniques are used in combination with FTIR for the
      identification of the comonomer type in coextruded films. A set of different
      LLDPE coextruded samples have been measured by FTIR, and the resulting spectra
      processed by Principal Component Analysis (PCA). By projecting the samples to the
      scores plots a difference is observed as a function of comonomer composition.
      This approach, compared with others is much faster, as just the time of measuring
      a film by direct infrared analysis is required.

PMID- 27886767
TI  - Preparation and characterization of magnetic molecularly imprinted polymers for
      the extraction of hexamethylenetetramine in milk samples.
AB  - Magnetic molecularly imprinted polymers (M-MIPs) were synthesized as the sorbents
      for extracting hexamethylenetetramine (HMT) from milk samples. Molecular
      simulations were used to calculate the interaction energies of the template
      monomers. The physical properties of M-MIPs were characterized. The adsorption
      isotherms and kinetics were investigated. Gas chromatography coupled with tandem
      mass spectrometry (GC-MS/MS) was applied to determine the amount of HMT residue
      in milk samples. In the optimized method, a linear calibration curve was obtained
      using a matrix-matched standard in the range of 1.0-50.0MUgL-1. The limit of
      detection (LOD) and limit of quantification (LOQ) was 0.3MUgkg-1 and 1.0MUgkg-1,
      respectively. The relative standard deviation (RSD) of the intra-day assay ranged
      from 2.6% to 5.2%, while that of the inter-day assay ranged from 3.6% to 11.5%.
      The recovery of HMT in milk samples ranged from 88.7% to 111.4%.

PMID- 27886770
TI  - Multiresidue method for trace pesticide analysis in honeybee wax comb by GC-QqQ
      MS.
AB  - The aim of this analytical study is to develop an improved multi-residue
      methodology of high sensitivity and expanded scope for pesticide residue analysis
      in honeybee wax combs. The method was validated for 160 pesticide residues
      (including acaricides, insecticides, fungicides and herbicides) gas
      chromatography amenable and covering a wide variety of polarity and chemical
      structure. This method of analysis applied gas chromatography coupled to a triple
      quadrupole mass spectrometer for the quantitative analysis of pesticide residues.
      The extraction procedure applied was based QuEChERs method allowing acceptable
      recoveries for most of the pesticides (98%), within the range 60-120% with an
      associated precision (RSD) <20%, at concentration levels of MQL of 10ugkg-1 for
      all pesticides with the exception of 3,5-dichloroaniline and chlordane (20ugkg
      1). The expanded uncertainty of the results was +/-35% on average (coverage
      factor k=2 for a confidence level of 95%). The chromatographic multi-residue
      method was applied to determine levels of pesticide residues in 50 honeybee wax
      comb samples randomly collected from different apiaries in Spain. A total of 32
      pesticide residues (14 insecticides/acaricides, 10 insecticides, 6 fungicides and
      2 herbicides) were detected in the samples. The highest pesticide concentrations
      were found for those with insecticide-acaricide activity like acrinathrin,
      chlorfenvinphos, coumaphos and fluvalinate-tau, some of them are mainly applied
      in apiculture for controlling the honeybee parasite Varroa destructor. The total
      load of pesticide residues ranged from 69 to 1000ugkg-1 for 40% of the analysed
      samples, 22% contained pesticide residues in the ranges of 1000-2000ugkg-1, 24%
      between 2000 and 5000ugkg-1 and 14% of the samples contained residues between
      5000 and 9557ugkg-1.

PMID- 27886771
TI  - A label-free electrochemical biosensor for microRNA detection based on catalytic
      hairpin assembly and in situ formation of molybdophosphate.
AB  - A label-free electrochemical biosensor for sensitive detection of miRNA-155 was
      presented by coupling enzyme-catalyzed in situ generation of electronic mediator
      for signal introduction with catalytic hairpin assembly (CHA) induced target
      recycling amplification strategy. In this work, alkaline phosphatase (ALP) was
      adopted to hydrolyze inactive substrate 1-naphthyl phosphate (NPP) to produce
      phosphate ion (PO43-), which could further react with acidic molybdate to form
      abundant molybdophosphate anion (PMo12O403-) on the surface of electrode. The
      produced PMo12O403- could directly generate a strong and stable electrochemical
      signal for quantitative detection of targets. In addition, CHA induced the cyclic
      reuse of the target was also employed as an effective strategy for improving the
      sensitivity of biosensor. This electrochemical method for miRNA-155 detection had
      achieved a good linear relationship ranging from 10fM to 1nM with a detection
      limit of 1.64fM. With this assay successfully applied in tumor cell lysates, it
      holds great potential for early cancer diagnosis by employing miRNA as the
      effective biomarker.

PMID- 27886772
TI  - Selective and sensitive electrochemical device for direct VB2 determination in
      real products.
AB  - The developed by us electrochemical device for vitamin B2 (VB2; riboflavin)
      determination, without preconcentration step, in real products exhibits high
      sensitivity, selectivity, stability and low detection limit compared to those
      described in the literature. The determination procedure was based on the
      monitoring of the reduction current signal of VB2 bound with dsDNA anchored to
      the electrode surface through intermediary - carboxyphenyl layer. The application
      of such intermediary layer formed during electroreduction of appropriate
      diazonium salt at CV peak potential guarantees high efficiency of hybridization
      process and thus fully available places for VB2 interaction. Moreover, such
      intermediary layer provides good electrical contact, what is very important in
      the case of electrochemical sensors. The analytical range of work of the proposed
      VB2 sensor was between 0.08-1uM (30-377MUgL-1) of riboflavin concentration. The
      obtained detection (LOD) and quantification limits (LOQ) were 24+/-2 and 55+/
      5MUgL-1, respectively. The proposed VB2 detection method was used for
      determination of riboflavin content in commercially available dietary supplements
      and yolk of hen egg samples. The accuracy of the obtained data was proved using
      comparison with an independent method (HPLC FLD).

PMID- 27886773
TI  - A novel aptameric biosensor based on the self-assembled DNA-WS2 nanosheet
      architecture.
AB  - It has been reported that tungsten disulfide (WS2) can bind single-stranded DNA
      (ssDNA) with high affinity while it has less affinity toward double stranded DNA
      (dsDNA). In this work, for the first time, the high affinity between WS2 and
      ssDNA was used to construct stable sensing interface for ATP detection. A DNA
      sequence with -SH at one end was first immobilized on Au electrode. WS2
      nanosheets were immobilized on the SH-DNA/Au electrode surface due to the strong
      affinity between WS2 and ssDNA. Then the WS2 nanosheets were used to immobilize
      ATP binding aptamer (ABA) through the high affinity between WS2 and ssDNA, too.
      When ATP reacts with the ABA aptamer, duplex will be formed and dissociated from
      the WS2 nanosheets. On the basis of this, an electrochemical aptasensor for ATP
      was fabricated. This ATP sensor showed high sensitivity, selectivity and
      stability due to the unique WS2-ssDNA interactions and the specific aptamer
      target recognition. Furthermore, this strategy was generalized to detect Hg2+
      using a mercury-specific aptamer (MSO). This strategy can be expected to offer a
      promising approach for designing high-performance electrochemical aptasensors for
      a spectrum of targets.

PMID- 27886774
TI  - Analysis of tricyclic antidepressants in human plasma using online-restricted
      access molecularly imprinted solid phase extraction followed by direct mass
      spectrometry identification/quantification.
AB  - The use of a new class of hybrid materials, called restricted access molecularly
      imprinted polymers (RAMIPs) seems to present a good strategy for the sample
      preparation of complex matrices, since these materials combine good protein
      elimination capacity with high degree selectivity. Mass spectrometers (MS) have
      been successfully used for polar drug identification and quantification. In order
      to combine the advantages of both RAMIPs and mass spectrometry, we proposed a
      study that joins these properties in a single system, where we could analyse
      tricyclic antidepressants from human plasma, without offline extraction or
      chromatographic separation. A RAMIP for amitriptyline was synthesised by the bulk
      method, using methacrylic acid as a functional monomer and glycidilmethacrylate
      as a hydrophilic co-monomer. Then, epoxide ring openings were made and the
      polymer was covered with bovine serum albumin (BSA). A column filled with RAMIP
      BSA was coupled to a MS/MS instrument in an online configuration, using water as
      loading and reconditioning mobile phase and a 0.01% acetic acid aqueous solution:
      acetonitrile at 30:70 as elution mobile phase. The system was used for on-line
      extraction and simultaneous quantification of nortriptyline, desipramine,
      amitriptyline, imipramine, clomipramine and clomipramine-d3 (IS) (from 15.0 to
      500.0MUgL-1) from plasma samples. The correlation coefficient was higher than
      0.99 for all analytes. The CV (coefficient of variation) values ranged from 1.34%
      to 19.13% for intra assay precision and 1.32-19.77% for inter assay precision.
      The E% (relative error) values ranged from -19.15% to 19.51% for intra assay
      accuracy and from -9.04% to 16.22% for inter assay accuracy.

PMID- 27886775
TI  - A simple, fast and sensitive screening LC-ESI-MS/MS method for antibiotics in
      fish.
AB  - The objective of this study was to develop and validate a fast, sensitive and
      simple liquid chromatography-electrospray ionization-tandem mass spectrometry (LC
      ESI-MS/MS) method for the screening of six classes of antibiotics
      (aminoglycosides, beta-lactams, macrolides, quinolones, sulfonamides and
      tetracyclines) in fish. Samples were extracted with trichloroacetic acid. LC
      separation was achieved on a Zorbax Eclipse XDB C18 column and gradient elution
      using 0.1% heptafluorobutyric acid in water and acetonitrile as mobile phase.
      Analysis was carried out in multiple reaction monitoring mode via electrospray
      interface operated in the positive ionization mode, with sulfaphenazole as
      internal standard. The method was suitable for routine screening purposes of 40
      antibiotics, according to EC Guidelines for the Validation of Screening Methods
      for Residues of Veterinary Medicines, taking into consideration threshold value,
      cut-off factor, detection capability, limit of detection, sensitivity and
      specificity. Real fish samples (n=193) from aquaculture were analyzed and 15%
      were positive for enrofloxacin (quinolone), one of them at a higher concentration
      than the level of interest (50ugkg-1), suggesting possible contamination or
      illegal use of that antibiotic.

PMID- 27886776
TI  - Synthesis and performance of chiral ferrocene modified silica gel for mixed-mode
      chromatography.
AB  - A brush-type chiral stationary phase, N-ferrocenyl benzoyl-(1S, 2R)-1, 2-diphenyl
      ethanol-bonded on the silica gel (NFcBEs) for high performance liquid
      chromatography (HPLC), was prepared using gamma-glycidoxypropyltrimethoxysilane
      as coupling reagent. The structure of this novel material was characterized by
      infrared spectroscopy, elemental analysis and thermogravimetric analysis.
      Mechanism involved in the chromatographic separation is the multi-interaction
      including hydrophobic, pi-pi, hydrogen-bonding, pi-charge transfer, dipole-dipole
      and acid-base equilibrium interactions. Based on these interactions, successful
      separation could be achieved among polycyclic aromatic hydrocarbons, mono
      substituted benzenes, aromatic amines, quinolines, nucleosides, phenols and 5
      nitroimidazoles drugs in reversed phase liquid chromatography (RPLC). Good
      resolutions for substituted amine isomers were also obtained with NFcBEs.
      Racemates of amino acids and drug carvedilol mixtures were well separated on
      NFcBEs in the normal phase liquid chromatography (NPLC) mode. Such stationary
      phase with characteristics of multi-interaction mechanism and mixed-mode
      separation is potential for the analysis of complex samples. The retention
      behaviors of R- and S-carvedilol on NFcBEs column were investigated with the
      assistance of quantum chemistry calculation using the density functional theory
      (DFT) B3LYP method.

PMID- 27886778
TI  - Editorial Comment.

PMID- 27886779
TI  - Editorial Comment.

PMID- 27886777
TI  - Characteristics of patients who are not resuscitated in out of hospital cardiac
      arrests and opportunities to improve community response to cardiac arrest.
AB  - AIM: This study explores why resuscitation is withheld when emergency medical
      staff arrive at the scene of a cardiac arrest and identifies modifiable factors
      associated with this decision. METHODS: This is a secondary analysis of
      unselected patients who sustained an out of hospital cardiac arrest attended by
      ambulance vehicles participating in a randomized controlled trial of a mechanical
      chest compression device (PARAMEDIC trial). Patients were categorized as 'non
      resuscitation' patients if there was a do-not-attempt-cardiopulmonary
      resuscitation (DNACPR) order, signs unequivocally associated with death or
      resuscitation was deemed futile (15min had elapsed since collapse with no
      bystander-CPR and asystole recorded on EMS arrival). RESULTS: Emergency Medical
      Services attended 11,451 cardiac arrests. Resuscitation was attempted or
      continued by Emergency Medical Service staff in 4805 (42%) of cases.
      Resuscitation was withheld in 6646 cases (58%). 711 (6.2%) had a do not attempt
      resuscitation decision, 4439 (38.8%) had signs unequivocally associated with
      death and in 1496 cases (13.1%) CPR was considered futile. Those where
      resuscitation was withheld due to futility were characterised by low bystander
      CPR rates (7.2%) and by being female. CONCLUSIONS: Resuscitation was withheld by
      ambulance staff in over one in ten (13.1%) victims of out of hospital cardiac
      arrest on the basis of futility. These cases were associated with a very low rate
      of bystander CPR. Future studies should explore strengthening the 'Chain of
      Survival' to increase the community bystander CPR response and evaluate the
      effect on the numbers of survivors from out of hospital cardiac arrest.

PMID- 27886781
TI  - Ambulatory Blood Pressure Monitoring: A Complementary Strategy for Hypertension
      Diagnosis and Management in Low-Income and Middle-Income Countries.
AB  - Ambulatory blood pressure monitoring (ABPM) can assess out-of-clinic blood
      pressure. ABPM is an underutilized resource in low-income and middle-income
      countries but should be considered a complementary strategy to clinic blood
      pressure measurement for the diagnosis and management of hypertension. Potential
      uses for ABPM in low-income and middle-income countries include screening of high
      risk individuals who have concurrent communicable diseases, such as HIV, and in
      task-shifting health care strategies.

PMID- 27886782
TI  - Ensuring Patient-Centered Access to Cardiovascular Disease Medicines in Low
      Income and Middle-Income Countries Through Health-System Strengthening.
AB  - Cardiovascular disease (CVD) is the leading cause of global mortality and is
      expected to reach 23 million deaths by 2030. Eighty percent of CVD deaths occur
      in low-income and middle-income countries (LMICs). Although CVD prevention and
      treatment guidelines are available, translating these into practice is hampered
      in LMICs by inadequate health care systems that limit access to lifesaving
      medications. In this review article, we describe the deficiencies in the current
      LMIC supply chains that limit access to effective CVD medicines, and discuss
      existing solutions that are translatable to similar settings so as to address
      these deficiencies.

PMID- 27886784
TI  - Tuberculosis and the Heart.
AB  - Owing to the high prevalence of tuberculosis (TB) and human immunodeficiency
      virus/AIDS, tuberculous heart disease remains an important problem in TB endemic
      areas. In this review, we reiterate salient aspects of the traditional
      understanding and approach to its management, and provide important updates on
      the pathophysiology, diagnosis, and treatment garnered over the past decade of
      focused clinical and basic science research. We emphasize that, if implemented
      widely, these improved evidence-based approaches to the disease can build on the
      early progress made in treating tuberculous heart disease and help further the
      goal of significantly reducing its historically high morbidity and mortality.

PMID- 27886780
TI  - Global Shifts in Cardiovascular Disease, the Epidemiologic Transition, and Other
      Contributing Factors: Toward a New Practice of Global Health Cardiology.
AB  - One of the major drivers of change in the practice of cardiology is population
      change. This article discusses the current debate about epidemiologic transition
      paired with other ongoing transitions with direct relevance to cardiovascular
      conditions. Challenges specific to patterns of risk factors over time; readiness
      for disease surveillance and meeting global targets; health system, prevention,
      and treatment efforts; and physiologic traits and human-environment interactions
      are identified. This article concludes that a focus on the most populated regions
      of the world will contribute substantially to protecting the large gains in
      global survival and life expectancy accrued over the last decades.

PMID- 27886783
TI  - mHealth Interventions to Counter Noncommunicable Diseases in Developing
      Countries: Still an Uncertain Promise.
AB  - mHealth constitutes a promise for health care delivery in low- and middle-income
      countries (LMICs) where health care systems are unprepared to combat the threat
      of noncommunicable diseases (NCDs). This article assesses the impact of mHealth
      on NCD outcomes in LMICs. A systematic review identified controlled studies
      evaluating mHealth interventions that addressed NCDs in LMICs. From the 1274
      abstracts retrieved, 108 articles were selected for full text review and 20
      randomized controlled trials were included from 14 LMICs. One-way SMS was the
      most commonly used mobile function to deliver reminders, health education, and
      information. mHealth interventions in LMICs have positive but modest effects on
      chronic disease outcomes.

PMID- 27886786
TI  - Infective Endocarditis in Low- and Middle-Income Countries.
AB  - Infective endocarditis (IE) is a rare, life-threatening disease with a mortality
      rate of 25% and significant debilitating morbidities. Although much has been
      reported on contemporary IE in high-income countries, conclusions on the state of
      IE in low- and middle-income countries (LMICs) are based on studies conducted
      before the year 2000. Furthermore, unique challenges in the diagnosis and
      management of IE persist in LMICs. This article reviews IE studies conducted in
      LMICs documenting clinical experiences from the year 2000 to 2016. Presented are
      the causes of IE, management of patients with IE, and prevailing challenges in
      diagnosis and treatment of IE in LMICs.

PMID- 27886785
TI  - Approaches to Sustainable Capacity Building for Cardiovascular Disease Care in
      Kenya.
AB  - Cardiovascular diseases are approaching epidemic levels in Kenya and other low-
      and middle-income countries without accompanying effective preventive and
      therapeutic strategies. This is happening in the background of residual and
      emerging infections and other diseases of poverty, and increasing physical
      injuries from traffic accidents and noncommunicable diseases. Investments to
      create a skilled workforce and health care infrastructure are needed. Improving
      diagnostic capacity, access to high-quality medications, health care, appropriate
      legislation, and proper coordination are key components to ensuring the reversal
      of the epidemic and a healthy citizenry. Strong partnerships with the developed
      countries also crucial.

PMID- 27886787
TI  - Rheumatic Heart Disease: The Unfinished Global Agenda.
AB  - Primarily affecting the young, rheumatic heart disease (RHD) is a neglected
      chronic disease commonly causing premature morbidity and mortality among the
      global poor. Standard clinical prevention and treatment is based on studies from
      the early antimicrobial era, as research investment halted soon after the virtual
      eradication of the disease from developed countries. The emergence of new global
      data on disease burden, new technologies, and a global health equity platform
      have revitalized interest and investment in RHD. This review surveys past and
      current evidence for standard RHD diagnosis and treatment, highlighting gaps in
      knowledge.

PMID- 27886788
TI  - Chagas Cardiomyopathy: Clinical Presentation and Management in the Americas.
AB  - The initial infection of Chagas disease is typically asymptomatic, but
      approximately 30% of people will progress to a chronic cardiac form, and others
      develop the gastrointestinal form. Death is often sudden due to arrhythmias or
      progressive heart failure. Prevention through vector control programs and blood
      bank screening, along with strengthened surveillance systems and rapid
      information sharing, are key to decreasing disease burden globally. The
      epidemiology, diagnostic evaluation, diagnosis, and treatment of acute and
      chronic Chagas cardiac disease are discussed with focus on educating the primary
      care professionals and general cardiologists in nonendemic areas who have limited
      experience treating this disease.

PMID- 27886789
TI  - Electrophysiology in the Developing World: Challenges and Opportunities.
AB  - As a subset of the growing epidemic of cardiovascular morbidity and mortality in
      low-income and middle-income countries (LMICs), the significant burdens of heart
      rhythm disorders also increase. Effective diagnostic and treatment modalities
      exist, but financial resources and expertise are limited. Cost-effective
      strategies exist to address most of these limitations, but many surmountable
      barriers need to be overcome to introduce and improve electrophysiologic care in
      LMICs. In this article, current and potential solutions are offered for the
      diagnostic and therapeutic challenges of managing bradyarrhythmias and
      tachyarrhythmias.

PMID- 27886790
TI  - Cardiac Disease Associated with Human Immunodeficiency Virus Infection.
AB  - Over the last 2 decades human immunodeficiency virus (HIV) infection has become a
      chronic disease requiring long-term management. Aging, antiretroviral therapy,
      chronic inflammation, and several other factors contribute to the increased risk
      of cardiovascular disease in patients infected with HIV. In low-income and middle
      income countries where antiretroviral therapy access is limited, cardiac disease
      is most commonly related to opportunistic infections and end-stage manifestations
      of HIV/acquired immunodeficiency syndrome, including HIV-associated
      cardiomyopathy, pericarditis, and pulmonary arterial hypertension. Cardiovascular
      screening, prevention, and risk factor management are important factors in the
      management of patients infected with HIV worldwide.

PMID- 27886792
TI  - Diagnosis and Management of Endomyocardial Fibrosis.
AB  - Endomyocardial fibrosis (EMF) remains an important cause of restrictive
      cardiomyopathy worldwide. Patients cluster in specific geographic locations and
      are almost universally living in extreme poverty. Specific etiology remains
      elusive and is likely multifactorial. Untreated EMF has a very poor prognosis.
      Medical management can mitigate symptoms for a time but has no curative benefit.
      Early surgical interventions may improve survival but are not readily available
      in most EMF-endemic regions. Increased awareness, advocacy, and research are
      needed to further understand this neglected tropical cardiomyopathy and to
      improve survival of those affected.

PMID- 27886794
TI  - Five Reasons Why Global Health Matters to Cardiologists.

PMID- 27886795
TI  - Miscellaneous inflammatory musculoskeletal conditions: Always a diagnostic and
      therapeutic challenge.

PMID- 27886796
TI  - Adult-onset Still's disease: Advances in the treatment.
AB  - Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder
      mainly characterized by persistent high spiking fevers, evanescent rash, and
      joint involvement. The pathogenesis of AOSD is only partially known, but pro
      inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1, IL-6, IL-18, and IFN-gamma seem to play a major role in this disorder.
      AOSD is at the crossroad of auto-inflammatory syndromes and autoimmune diseases.
      It is diagnosed by exclusion to determine the presence of high serum ferritin
      levels, which is usually >1000 MUg/L. AOSD is generally treated with non
      steroidal anti-inflammatory drugs, corticosteroids, and disease-modifying anti
      rheumatic drugs (DMARDs). Although information on biologic therapy in the
      management of AOSD is scarce, these drugs represent a major breakthrough in the
      management of patients with AOSD refractory to corticosteroids or conventional
      DMARDs or in patients presenting life-threatening manifestations. In this regard,
      TNF-alpha, IL-1, and IL-6 antagonists had been proved effective in patients with
      AOSD.

PMID- 27886791
TI  - Environmental Exposures and Cardiovascular Disease: A Challenge for Health and
      Development in Low- and Middle-Income Countries.
AB  - Environmental exposures in low- and middle-income countries lie at the
      intersection of increased economic development and the rising public health
      burden of cardiovascular disease. Increasing evidence suggests an association of
      exposure to ambient air pollution, household air pollution from biomass fuel,
      lead, arsenic, and cadmium with multiple cardiovascular disease outcomes,
      including hypertension, coronary heart disease, stroke, and cardiovascular
      mortality. Although populations in low- and middle-income countries are
      disproportionately exposed to environmental pollution, evidence linking these
      exposures to cardiovascular disease is derived from populations in high-income
      countries. More research is needed to further characterize the extent of
      environmental exposures.

PMID- 27886797
TI  - Catastrophic antiphospholipid syndrome: The current management approach.
AB  - The current recommendation for catastrophic antiphospholipid syndrome (CAPS)
      management is the standard triple therapy with anticoagulation (AC),
      glucocorticoids (GCs), plasma exchange (PE), and/or intravenous immunoglobulins
      (IVIGs). Of note, only AC has a significant effect on the prognosis of these
      patients. However, from the experimental or basic point of view, there is only
      indirect evidence to advocate the use of these immunomodulatory therapies (GC,
      PE, and IVIG) in CAPS. Recently, there have been reports of severe or refractory
      CAPS patients treated with the monoclonal antibodies rituximab and eculizumab.
      The first blocks CD20, a surface protein expressed on the cytoplasmic membrane of
      B cells, and decreases the generation of pathogenic autoantibodies such as
      antiphospholipid (aPL) antibodies. The second binds with high affinity to C5
      complement protein, inhibiting its cleavage and thus preventing the generation of
      C5b-C9 complex.

PMID- 27886793
TI  - Innovative Approaches to Hypertension Control in Low- and Middle-Income
      Countries.
AB  - Elevated blood pressure, a major risk factor for ischemic heart disease, heart
      failure, and stroke, is the leading global risk for mortality. Treatment and
      control rates are very low in low- and middle-income countries. There is an
      urgent need to address this problem. The Global Alliance for Chronic Diseases
      sponsored research projects focus on controlling hypertension, including
      community engagement, salt reduction, salt substitution, task redistribution,
      mHealth, and fixed-dose combination therapies. This paper reviews the rationale
      for each approach and summarizes the experience of some of the research teams.
      The studies demonstrate innovative and practical methods for improving
      hypertension control.

PMID- 27886798
TI  - Multicentric reticulohistiocytosis: Rheumatology perspective.
AB  - Multicentric reticulohistiocytosis (MRH) is a rare, multisystemic non-Langerhans
      cell histiocytosis characterized by skin and articular involvement, and rarely
      involves various other organs. There are no specific laboratory findings for MRH.
      Diagnosis is based on clinical findings and skin or synovial biopsy results.
      There is currently no consensus for the treatment of MRH. Here, we review the
      differential diagnosis and treatment options of MRH from the rheumatologist's
      perspective. We also report an index case of MRH associated with Sjogren's
      syndrome and pulmonary embolism.

PMID- 27886799
TI  - IgG4-related disease: Advances in the diagnosis and treatment.
AB  - IgG4-related disease is a rare immune-mediated systemic disease with the
      capability of involving essentially any organ. Although the presenting clinical
      features vary substantially according to the speciality to which patients present
      first, perhaps the most common clinical presentation is that of single or
      multiple organ enlargement, arousing suspicion of cancer. The disease is
      frequently diagnosed unexpectedly in pathological specimens or on imaging
      studies. The diagnostic approach is complex and includes not only IgG4-related
      tests (serum levels, circulating plasmablasts, and specific immunohistochemical
      studies), but also clinical, laboratory, and imaging tests as well as the typical
      histopathological features (lymphocytic infiltration, storiform fibrosis,
      eosinophilic infiltration, and obliterative phlebitis). IgG4-related tests should
      not be considered as diagnostic in the absence of an appropriate clinical
      scenario. Therapeutic approaches reported to date pertain primarily to
      glucocorticoids, but the use of these medications has not been studied in a
      controlled or prospective manner. The most current investigational treatment
      approaches have focused on targeting cells of the B-cell lineage, including B
      cell-depleting agents (rituximab) and a non-depleting homodimer monoclonal
      antibody targeting CD19 and Fc-gamma RIIIb.

PMID- 27886800
TI  - Behcet's disease: How to diagnose and treat vascular involvement.
AB  - Behcet's disease is a multisystem disorder with unknown etiology and a unique
      geographic distribution. The disease is characterized by recurrent skin-mucosa
      lesions and sight-threatening panuveitis. Vascular involvement, which is more
      common and more severe among males, has also equally characteristic features such
      as affecting mostly veins, having a significant tendency for thrombosis, and
      running a relapsing course. Lower extremity vein thrombosis (LEVT) is the most
      frequent manifestation, followed by vena cava inferior thrombosis. Pulmonary
      artery involvement (PAI), the most common form of arterial involvement, manifests
      as aneurysms and "in situ" thrombosis. PAI and Budd-Chiari syndrome are the
      leading causes of increased mortality. In vascular cluster, typically, several
      types of venous or arterial vascular involvement may accumulate in the same
      individual. LEVT or cerebral venous sinus thrombosis is often present in these
      subgroups as the first event. Immunosuppressive treatment is essential in
      preventing the attacks and increasing survival.

PMID- 27886801
TI  - Approach to the patients with inadequate response to colchicine in familial
      Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is the most common form of monogenic
      autoinflammatory conditions, and response to colchicine has been considered as
      one of its distinctive features among other hereditary periodic fever disorders.
      Prophylactic colchicine has been shown to be effective in the prevention of
      inflammatory attacks and development of amyloidosis. However, the highest
      tolerable doses of colchicine may not be adequate enough to manage these goals in
      approximately 5% of FMF patients. Inadequate response to colchicine in fully
      compliant FMF patients may be associated with genetic and/or environmental
      factors affecting disease severity and colchicine bioavailability. Clarification
      of the molecular pathogenic mechanisms of FMF has revealed that interleukin-1
      beta (IL-1beta) cytokine is the most likely target to attack, and several case
      reports and case series have already documented the efficacy and safety of
      available anti-IL-1 agents, such as anakinra, rilonacept, and canakinumab in
      those patients inadequately responding to colchicine. Characterization and early
      identification of those FMF patients with uncontrolled inflammatory activity have
      become more important after the availability of new treatment options for the
      prevention of disease-associated complications and permanent damages.

PMID- 27886802
TI  - Advancements in the management of uveitis.
AB  - Uveitis may exist as a clinical manifestation of an underlying systemic disease
      or may represent an idiopathic entity, sometimes with a very characteristic
      pattern. Different forms of uveitis have been defined on the basis of three
      important variables: chronicity, anatomic location, and underlying etiology. The
      evolving understanding of the immune system has resulted in a more targeted
      approach to manage patients with different forms of uveitis, although clearly
      this approach is at a very early stage. Altered patterns of cellular processing
      and different cytokine expression, including TNF, IL-1, IL-2, IL-6, and IL17,
      have been defined in uveitis, and this has laid the pathway for targeted therapy.
      Furthermore, approved biologic therapies for some of the more common autoimmune
      illnesses have now been tested in uveitis. Adalimumab and infliximab have been
      the best studied anti-TNF agents and indeed have now been recommended by an
      expert panel as the first line of treatment for ocular manifestations of Behcet's
      disease and the second line of treatment for other forms of uveitis. Adalimumab
      has been recently approved for intermediate uveitis, posterior uveitis, and
      panuveitis. Other biologic agents have been tested, including daclizumab, a
      monoclonal antibody directed against IL-2, anti-IL1, and anti-IL-6 receptor
      agents and therapies that block antigen-presenting cell and T-cell interaction,
      such as abatacept. In small case series, other biologics such as interferon and
      rituximab have also been evaluated. Although these biologic therapies have
      provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is
      not a disease, but a manifestation of many potential systemic diseases that may
      have specific individual therapeutic targets. Identification and characterization
      of these underlying diseases are not always possible and, more importantly, the
      most effective therapies for each entity have not been defined. In this study, an
      approach to manage patients with uveitis is presented and current therapy is
      reviewed.

PMID- 27886804
TI  - Sarcoidosis: Rheumatology perspective.
AB  - Sarcoidosis is a systemic inflammatory granulomatous disease for which
      rheumatologists are uniquely trained and qualified to treat. Historically,
      sarcoidosis has been managed within silos of medical subspecialties, but with
      increased appreciation of the systemic nature of this disorder and the
      availability of more therapeutic options, it is clear that a multidisciplinary
      approach, with the rheumatologist as a key component, can offer more optimal
      care. This manuscript reviews clinically relevant immunology and pathophysiology,
      diagnostic issues, management decision-making, and therapeutics in the care of
      patients with sarcoidosis. Issues particularly relevant to rheumatologists are
      highlighted. These include aiding in establishing diagnosis; recognition of
      disease manifestations involving bone, joint, and muscle; management of calcium
      metabolism and metabolic bone disease; and formulation and implementation of anti
      inflammatory and immunomodulatory therapies.

PMID- 27886803
TI  - Relapsing polychondritis: A 2016 update on clinical features, diagnostic tools,
      treatment and biological drug use.
AB  - Relapsing polychondritis (RP) is a very rare autoimmune disease characterised by
      a relapsing inflammation of the cartilaginous tissues (joints, ears, nose,
      intervertebral discs, larynx, trachea and cartilaginous bronchi), which may
      progress to long-lasting atrophy and/or deformity of the cartilages. Non
      cartilaginous tissues may also be affected, such as the eyes, heart, aorta, inner
      ear and skin. RP has a long and unpredictable course. Because no randomised
      therapeutic trials are available, the treatment of RP remains mainly empirical.
      Minor forms of the disease can be treated with non-steroidal anti-inflammatory
      drugs, whereas more severe forms are treated with systemic corticosteroids. Life
      threatening diseases and corticosteroid-dependent or resistant diseases are an
      indication for immunosuppressant therapy such as methotrexate, azathioprine,
      mycophenolate mofetil and cyclophosphamide. Biologics could be given as second
      line treatment in patients with an active disease despite the use of steroids and
      immunosuppressive drugs. Although the biologics represent new potential treatment
      for RP, very scarce information is available to draw any firm conclusion on their
      use in RP.

PMID- 27886805
TI  - Prevalence and factors associated with smoking among adolescents.
AB  - OBJECTIVE: Despite anti-smoking prevention programs, many adolescents start
      smoking at school age. The main objectives of this study were to determine the
      prevalence and risk factors associated with smoking in adolescents living in
      Uruguaiana, RS, Brazil. METHODS: A prospective study was conducted in adolescents
      (12-19 years), enrolled in municipal schools, who answered a self-administered
      questionnaire on smoking. RESULTS: 798 adolescents were enrolled in the study,
      with equal distribution between genders. The tobacco experimentation frequency
      (ever tried a cigarette, even one or two puffs) was 29.3%; 14.5% started smoking
      before 12 years of age and 13.0% reported smoking at least one cigarette/day last
      month. Having a smoking friend (OR: 5.67, 95% CI: 2.06-7.09), having cigarettes
      offered by friends (OR: 4.21, 95% CI: 2.46-5.76) and having easy access to
      cigarettes (OR: 3.82, 95% CI: 1.22-5.41) was identified as factors associated
      with smoking. Having parental guidance on smoking (OR: 0.67, 95% CI: 0.45-0.77),
      having no contact with cigarettes at home in the last week (OR: 0.51, 95% CI:
      0.11-0.79) and knowing about the dangers of electronic cigarettes (OR: 0.88, 95%
      CI: 0.21-0.92) were identified as protection factors. CONCLUSION: The prevalence
      of smoking among adolescents in Uruguaiana is high. The implementation of
      measures to reduce/stop tobacco use and its new forms of consumption, such as
      electronic cigarettes and hookah, are urgent and imperative in schools.

PMID- 27886806
TI  - Psychopathology, quality of life, and related factors in children with celiac
      disease.
AB  - OBJECTIVE: This study aimed to survey children with celiac disease (CD) for
      psychiatric disorders, determine the possible factors that predict
      psychopathology, and analyze health-related quality of life and possible factors
      that could affect the quality of life. METHODS: In this study, all children
      completed the Schedule for Affective Disorders and Schizophrenia for School Age
      Children - Present and Lifetime Version - Turkish Version (K-SADS-PL-T), as well
      as the Pediatric Quality of Life Inventory (PedsQL) for the 8-12 age group, and a
      sentence completion test. A face-to-face interview was performed with the parents
      of the participants to inform them about the study. RESULTS: This study included
      52 children with celiac disease in the age range of 8-12 years, and 40 healthy
      children. The mean age of the study group was 10.36+/-0.36 years, and 31 (59%) of
      them were females. The mean age of the control group was 10.35+/-0.46 years and
      24 (60%) of them were females. The mean subscale scores of the Pediatric Quality
      of Life Inventory were significantly lower in children with celiac disease when
      compared to the control group (p<0.05). There was at least one psychiatric
      disorder in the 26 (50%) children with celiac disease. CONCLUSIONS: This study
      has shown once more that celiac disease is associated with some psychiatric
      signs/diagnoses, and that it decreased quality of life. Further studies are
      needed to determine the factors that could reduce the psychiatric signs. It is
      apparent that those studies would contribute new approaches to improve diagnosis,
      treatment, and quality of life.

PMID- 27886807
TI  - A method for the assessment of facial hedonic reactions in newborns.
AB  - OBJECTIVE: This study describes a quantitative and qualitative methodology to
      assess hedonic responses to sweet stimulus in healthy newborns. METHODS: A
      descriptive, cross-sectional, observational study, with healthy newborns (up to
      24h of life), between 37 and 42 gestational weeks, vaginally born and breastfed
      previously to all tests. The evaluation of the newborns reactions was performed
      by hedonic facial expression analysis, characterized by facial expressions with
      rhythmic serial tongue protrusion after neutral or sweet solution intake.
      Initially, 1mL of water solution was provided to the newborn, followed by a 1
      minute recording. Afterwards, the same amount of 25% sucrose solution was
      provided, performing a second recording. The concordance between researchers was
      analyzed by the Bland-Altman statistical method. RESULTS: A total of 100 newborns
      (n=49 males, n=51 females; mean lifetime=15h 12min+/-6h 29min) were recorded for
      neutral and sucrose solution intake, totaling 197 videos (n=3 missing in the
      water treatment). These videos were double-blind analyzed and the test revealed a
      90% concordance between the two trained researchers, in relation to both
      solutions. The intraclass correlation coefficient was 0.99 for both solutions,
      with a significant increase in frequency of hedonic expressions evoked by sucrose
      solution intake. CONCLUSIONS: These results confirm that the proposed method has
      an efficient power to detect significant differences between neutral and sucrose
      stimuli. In conclusion, this evaluation method of hedonic facial reactions in
      newborns reflects the response to a specific taste.

PMID- 27886809
TI  - Small mammal utilization by Middle Stone Age humans at Die Kelders Cave 1 and
      Pinnacle Point Site 5-6, Western Cape Province, South Africa.
AB  - Reported here are the results of a taphonomic analysis of the small mammals
      (between 0.75 kg and 4.5 kg adult body weight) and size 1 bovids (<=20 kg adult
      body weight) from the Middle Stone Age (MSA) sites of Die Kelders Cave 1 (DK1)
      and Pinnacle Point Site 5-6 (PP5-6), Western Cape Province, South Africa. This
      study provides a comprehensive taphonomic analysis of MSA small mammals with a
      focus on discerning the role of humans in their accumulation and the implications
      for human behavioral adaptations. Based on comparisons with control assemblages
      of known accumulation, it is evident that humans accumulated many of the Cape
      dune mole-rats, hares, and size 1 bovids at DK1. The patterning of cut-marked and
      burned mole-rat remains at DK1 provides evidence in the MSA for the systematic
      utilization of small mammals for their skins and as a protein source. Unlike DK1,
      small mammals and size 1 bovids constitute only a small portion of the PP5-6
      mammals and they exhibit little evidence of human accumulation. Nocturnal and
      diurnal raptors accumulated most of the small fauna at PP5-6. The nominal
      presence of small mammals in the PP5-6 fauna is atypical of MSA sites in the Cape
      Floristic Region, where they are abundant and often constitute large portions of
      MSA archaeofaunas. DK1 humans maximized the environmental yield by exploiting low
      quality resources, a strategy employed possibly in response to localized
      environmental conditions and to greater human population densities. In
      comparison, the MIS5-4 humans at PP5-6 did not exploit small mammals and instead
      focused on higher-quality resources like shellfish and large ungulates. Humans
      and predators accumulated few small mammals at PP5-6, suggesting that these taxa
      may have been less abundant near the site and/or that humans could afford to
      concentrate on high-quality resources, perhaps because of a higher-yield local
      environment. This study suggests that an adaptive response to the environmental
      conditions of MIS4 was to maximize the resource yield of local habitats to
      include lower-quality resources when necessary. The incorporation of these
      resources in the face of changing environmental and perhaps population pressures
      is a subsistence adaptation that played a crucial role in the population
      stability and expansion evidenced by the number of sites in the Cape dating to
      MIS4.

PMID- 27886808
TI  - Comparative isotope ecology of African great apes.
AB  - The isotope ecology of great apes is a useful reference for palaeodietary
      reconstructions in fossil hominins. As extant apes live in C3-dominated habitats,
      variation in isotope signatures is assumed to be low compared to hominoids
      exploiting C4-plant resources. However, isotopic differences between sites and
      between and within individuals are poorly understood due to the lack of
      vegetation baseline data. In this comparative study, we included all species of
      free-ranging African great apes (Pan troglodytes, Pan paniscus, Gorilla sp.).
      First, we explore differences in isotope baselines across different habitats and
      whether isotopic signatures in apes can be related to feeding niches (faunivory
      and folivory). Secondly, we illustrate how stable isotopic variations within
      African ape populations compare to other extant and extinct primates and discuss
      possible implications for dietary flexibility. Using 701 carbon and nitrogen
      isotope data points resulting from 148 sectioned hair samples and an additional
      collection of 189 fruit samples, we compare six different great ape sites. We
      investigate the relationship between vegetation baselines and climatic variables,
      and subsequently correct great ape isotope data to a standardized plant baseline
      from the respective sites. We obtained temporal isotopic profiles of individual
      animals by sectioning hair along its growth trajectory. Isotopic signatures of
      great apes differed between sites, mainly as vegetation isotope baselines were
      correlated with site-specific climatic conditions. We show that controlling for
      plant isotopic characteristics at a given site is essential for faunal data
      interpretation. While accounting for plant baseline effects, we found distinct
      isotopic profiles for each great ape population. Based on evidence from
      habituated groups and sympatric great ape species, these differences could
      possibly be related to faunivory and folivory. Dietary flexibility in apes
      varied, but temporal variation was overall lower than in fossil hominins and
      extant baboons, shifting from C3 to C4-resources, providing new perspectives on
      comparisons between extinct and extant primates.

PMID- 27886810
TI  - Early modern human lithic technology from Jerimalai, East Timor.
AB  - Jerimalai is a rock shelter in East Timor with cultural remains dated to 42,000
      years ago, making it one of the oldest known sites of modern human activity in
      island Southeast Asia. It has special global significance for its record of early
      pelagic fishing and ancient shell fish hooks. It is also of regional significance
      for its early occupation and comparatively large assemblage of Pleistocene stone
      artefacts. Three major findings arise from our study of the stone artefacts.
      First, there is little change in lithic technology over the 42,000 year sequence,
      with the most noticeable change being the addition of new artefact types and raw
      materials in the mid-Holocene. Second, the assemblage is dominated by small chert
      cores and implements rather than pebble tools and choppers, a pattern we argue
      pattern, we argue, that is common in island SE Asian sites as opposed to mainland
      SE Asian sites. Third, the Jerimalai assemblage bears a striking resemblance to
      the assemblage from Liang Bua, argued by the Liang Bua excavation team to be
      associated with Homo floresiensis. We argue that the near proximity of these two
      islands along the Indonesian island chain (c.100 km apart), the long antiquity of
      modern human occupation in the region (as documented at Jerimalai), and the
      strong resemblance of distinctive flake stone technologies seen at both sites,
      raises the intriguing possibility that both the Liang Bua and Jerimalai
      assemblages were created by modern humans.

PMID- 27886811
TI  - Morphoarchitectural variation in South African fossil cercopithecoid endocasts.
AB  - Despite the abundance of well-preserved crania and natural endocasts in the South
      African Plio-Pleistocene cercopithecoid record, which provide direct information
      relevant to the evolution of their endocranial characteristics, few studies have
      attempted to characterize patterns of external brain morphology in this highly
      successful primate Superfamily. The availability of non-destructive penetrating
      radiation imaging systems, together with recently developed computer-based
      analytical tools, allow for high resolution virtual imaging and modeling of the
      endocranial casts and thus disclose new perspectives in comparative
      paleoneurology. Here, we use X-ray microtomographic-based 3D virtual imaging and
      quantitative analyses to investigate the endocranial organization of 14
      cercopithecoid specimens from the South African sites of Makapansgat,
      Sterkfontein, Swartkrans, and Taung. We present the first detailed comparative
      description of the external neuroanatomies that characterize these Plio
      Pleistocene primates. Along with reconstruction of endocranial volumes, we
      combine a semi-automatic technique for extracting the neocortical sulcal pattern
      together with a landmark-free surface deformation method to investigate
      topographic differences in morphostructural organization. Besides providing and
      comparing for the first time endocranial volume estimates of extinct Plio
      Pleistocene South African cercopithecoid taxa, we report additional information
      regarding the variation in the sulcal pattern of Theropithecus oswaldi
      subspecies, and notably of the central sulcus, and the neuroanatomical condition
      of the colobine taxon Cercopithecoides williamsi, suggested to be similar for
      some aspects to the papionin pattern, and discuss potential phylogenetic and
      taxonomic implications. Further research in virtual paleoneurology, applied to
      specimens from a wider geographic area, is needed to clarify the polarity,
      intensity, and timing of cortical surface evolution in cercopithecoid lineages.

PMID- 27886812
TI  - Foraging potential of underground storage organ plants in the southern Cape,
      South Africa.
AB  - Underground storage organs (USOs) serve as a staple source of carbohydrates for
      many hunter-gatherer societies and they feature prominently in discussions of
      diets of early modern humans. While the way of life of hunter-gatherers in South
      Africa's Cape no longer exists, there is extensive ethnographic, historical, and
      archaeological evidence of hunter-gatherers' use of USOs. This is to be expected,
      given that the Cape supports the largest concentration of plant species with USOs
      globally. The southern Cape is the location of several Middle Stone Age sites
      that are highly significant to research on the origins of behaviourally modern
      humans, and this provided the context for our research. Here, we evaluate the
      foraging potential of USOs by identifying how abundant edible biomass is in the
      southern Cape, how easily it is gathered, and how nutritious it is. One hundred 5
      * 5 m plots were assessed in terms of USO species and abundance. Nearly all of
      the sites sampled (83%) contained edible USOs and some had high concentrations of
      edible biomass. Extrapolating from these sites suggests that the edible USO
      biomass falls within the range of biomass observed in areas supporting extant
      hunter-gatherer communities. The nutritional content for six USO species was
      assessed; these contained between 40 and 228 calories/100 g. Furthermore,
      foraging events were staged to provide an indication of the potential return
      rates for the same six USOs. The target species grow near the soil surface,
      mostly in sandy soils, and were gathered with minimal effort. Some 50% of the
      foraging events conducted yielded enough calories to meet the daily requirements
      of a hunter-gatherer within two hours. In conclusion, we demonstrate that USOs
      are a readily available source of carbohydrates in the southern Cape landscape
      and, therefore, there is a strong possibility that USOs played a critical role in
      providing food for early humans.

PMID- 27886813
TI  - Cranial vault thickness in non-human primates: Allometric and geometric analyses
      of the vault and its component layers.
AB  - Extremely thick cranial vaults have been noted as a diagnostic characteristic of
      Homo erectus since the first fossil of the species was identified, but relatively
      little work has been done on elucidating its variation within extant non-human
      primates. Cranial vault thickness (CVT) is not a monolithic trait, and the
      relationship of its layers to other morphological variables is unknown. Total CVT
      and the thickness of the cortical and diploe layers individually, as well as the
      ratio between diploe and total thickness, were calculated from 258 female
      individuals from 47 species of non-human primate. Measures of CVT were then
      regressed onto measures of body, brain, vault, facial, and mandibular size as
      well as vault shape. Total frontal and parietal CVT scales with positive
      allometry or isometry with measures of size across a combined non-human primate
      sample, although some variation exists within each infraorder and when diploe
      thickness alone is compared to measures of size. CVT in this sample correlates
      weakly with cranial vault shape, but the relationship described here contradicts
      an earlier hypothesis that long, low vaults should be thicker than higher,
      globular vaults. This study provides new data on the variation of vault
      morphology among extant primates that may be used to inform future hypotheses for
      the cranial vault hypertrophy of H. erectus.

PMID- 27886815
TI  - Antiplatelet Therapy for Secondary Prevention After Acute Myocardial Infarction.
AB  - Patients with prior myocardial infarction (MI) are at long-term heightened risk
      for recurrent ischemic events. Several large randomized controlled trials have
      demonstrated the benefit of more intensive antiplatelet strategies for long-term
      secondary prevention of cardiovascular death, recurrent MI, and stroke in
      patients with a history of MI at a cost of increased bleeding. The bleeding risk
      associated with long-term intensive antiplatelet strategies requires careful
      patient selection and involvement of patients in shared decision making regarding
      risks and benefits of therapy. Clinical characteristics, adherence to therapy,
      and integrated risk scores may aid clinicians in translating clinical trials into
      individualized therapy.

PMID- 27886816
TI  - Pretreatment with Antiplatelet Agents in the Setting of Percutaneous Coronary
      Intervention: When and Which Drugs?
AB  - Administering antiplatelet agents before coronary angiography to patients
      referred to elective or urgent percutaneous coronary intervention (PCI) requires
      a careful evaluation of advantages and disadvantages associated with platelet
      inhibition to avoid overtreatment on one side and undertreatment on the other.
      The delicate balance between ischemic protection and bleeding demands the ability
      to undertake risk stratification and individualized decisions, which is
      particularly challenging in the setting of ad hoc PCI and urgent procedures. This
      review analyzes the current evidence on pretreatment with oral and intravenous
      P2Y12 inhibitors in patients undergoing coronary angiography with intent to
      undergo PCI.

PMID- 27886814
TI  - Regulation of Platelet Activation and Coagulation and Its Role in Vascular Injury
      and Arterial Thrombosis.
AB  - Hemostasis requires tightly regulated interaction of the coagulation system,
      platelets, blood cells, and vessel wall components at a site of vascular injury.
      Dysregulation of this response may result in excessive bleeding if the response
      is impaired, and pathologic thrombosis with vessel occlusion and tissue ischemia
      if the response is robust. Studies have elucidated the major molecular signaling
      pathways responsible for platelet activation and aggregation. Antithrombotic
      agents targeting these pathways are in clinical use. This review summarizes
      research examining mechanisms by which these multiple platelet signaling pathways
      are integrated at a site of vascular injury to produce an optimal hemostatic
      response.

PMID- 27886817
TI  - Antithrombotic Therapy to Reduce Ischemic Events in Acute Coronary Syndromes
      Patients Undergoing Percutaneous Coronary Intervention.
AB  - Antithrombotic therapy is essential in the prevention of periprocedural death and
      myocardial infarction during and after percutaneous coronary intervention. In the
      pathogenesis of acute coronary syndromes (ACS), both platelets and the
      coagulation cascade play an important role. Therefore, periprocedural
      antithrombotic therapy is even more important in ACS than in elective PCI. The
      most used agents are aspirin, platelet P2Y12 blockers, platelet glycoprotein
      IIb/IIIa blockers, and parenteral anticoagulants. The P2Y12 blockers must be
      continued at least 12 months. High-risk patients should be treated with
      glycoprotein IIb/IIIa receptor antagonists, especially those undergoing primary
      angioplasty for ST-elevation acute coronary syndrome.

PMID- 27886819
TI  - Current Role of Platelet Function Testing in Percutaneous Coronary Intervention
      and Coronary Artery Bypass Grafting.
AB  - There is interindividual variability in the pharmacodynamic response to
      antiplatelet medications. High on-treatment platelet reactivity, reflecting a
      failure to achieve adequate platelet inhibition, is associated with a higher risk
      for thrombotic events. Low on-treatment platelet reactivity, or an enhanced
      response to antiplatelet medications, has been linked to a higher risk for
      bleeding. There is evidence for the prognostic value of platelet function testing
      for risk prediction. This review presents the current evidence regarding platelet
      function testing in patients undergoing percutaneous cardiac intervention and
      coronary artery bypass grafting. The possible role of platelet function testing
      for individualized antiplatelet treatment is highlighted.

PMID- 27886820
TI  - Optimal Duration of Dual Antiplatelet Therapy After Percutaneous Coronary
      Intervention.
AB  - Dual antiplatelet therapy (DAPT) is an essential component of treatment in
      patients with coronary artery disease treated with percutaneous coronary
      intervention (PCI). Recommendations for duration of DAPT after PCI should
      consider patient-specific risk, clinical presentation, stent characteristics, and
      procedural factors. Prolonged DAPT results in a reduction of stent thrombosis
      (ST) and myocardial infarction (MI) at the cost of increased bleeding. Studies of
      shorter-duration DAPT demonstrate similar mortality, MI, ST, and less bleeding
      when compared with longer DAPT duration. We review current evidence for
      strategies of prolonged DAPT and abbreviated DAPT following PCI.

PMID- 27886818
TI  - Genetic Determinants of P2Y12 Inhibitors and Clinical Implications.
AB  - There is significant interpatient variability in clopidogrel effectiveness, which
      is due in part to cytochrome P450 (CYP) 2C19 genotype. Approximately 30% of
      individuals carry CYP2C19 loss-of-function alleles, which have been consistently
      shown to reduce clopidogrel effectiveness after an acute coronary syndrome and
      percutaneous coronary intervention. Guidelines recommend consideration of
      prasugrel or ticagrelor in these patients. A clinical trial examining outcomes
      with CYP2C19 genotype-guided antiplatelet therapy is ongoing. In the meantime,
      based on the evidence available to date, several institutions have started
      clinically implementing CYP2C19 genotyping to assist with antiplatelet selection
      after percutaneous coronary intervention.

PMID- 27886821
TI  - Cangrelor: Pharmacology, Clinical Data, and Role in Percutaneous Coronary
      Intervention.
AB  - In clinical trials that assessed the safety and efficacy of cangrelor during
      percutaneous coronary intervention (PCI), cangrelor was administered as a 30
      MUg/kg bolus followed by a 4-MUg/kg/min infusion for at least 2 hours or the
      duration of the PCI, whichever was longer. Cangrelor is currently indicated as an
      adjunct to PCI to reduce the risk of myocardial infarction, repeat coronary
      revascularization, and stent thrombosis in patients who have not been treated
      with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa
      inhibitor.

PMID- 27886822
TI  - Ticagrelor: Effects Beyond the P2Y12 Receptor.
AB  - Platelet P2Y12 receptor inhibitors are crucial in the treatment of patients with
      acute coronary syndrome or undergoing percutaneous coronary intervention.
      Ticagrelor is a reversibly binding, potent oral P2Y12 inhibitor that also is a
      weak inhibitor of the equilibrative nucleoside transporter-1 pathway for cellular
      adenosine uptake. It is hypothesized that ticagrelor has clinically relevant "off
      target" effects, independent of its effect on platelet aggregation and
      thrombosis. This review considers the pleiotropic effects of ticagrelor and some
      of the possible mechanisms related to these effects.

PMID- 27886823
TI  - Protease-Activated Receptor-1 Antagonists Post-Percutaneous Coronary
      Intervention.
AB  - Thrombin is a potent platelet agonist, and protease-activated receptor-1 (PAR-1)
      is the main thrombin receptor in human platelets and thrombin. PAR-1 antagonism
      has attracted interest as a potential therapeutic target to reduce
      atherothrombotic events in patients with atherosclerotic disease, especially
      coronary artery disease. In this review, the author describes the rationale of
      PAR-1 antagonism for the reduction of atherothrombotic events and reviews the key
      phase 3 trial results, with special attention to analyses in percutaneous
      coronary intervention patients.

PMID- 27886824
TI  - Switching P2Y12 Receptor Inhibiting Therapies.
AB  - Antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor is the
      cornerstone of treatment of patients with atherothrombotic disease
      manifestations. Switching between P2Y12 inhibitors occurs commonly in clinical
      practice for a variety of reasons, including safety, efficacy, adherence, and
      economic considerations. There are concerns about the optimal approach for
      switching because of potential drug interactions, which may lead to ineffective
      platelet inhibition and thrombotic complications, or potential overdosing due to
      overlap in drug therapy, which might cause excessive platelet inhibition and
      increased bleeding. This review provides practical considerations of switching
      based on pharmacodynamic and clinical data available from the literature.

PMID- 27886825
TI  - Antiplatelet and Antithrombotic Therapy in Patients with Atrial Fibrillation
      Undergoing Coronary Stenting.
AB  - Stroke prevention is the main priority in the management cascade of atrial
      fibrillation. Most patients require long-term oral anticoagulation (OAC) and may
      require percutaneous coronary intervention. Prevention of recurrent cardiac
      ischemia and stent thrombosis necessitate dual antiplatelet therapy (DAPT) for up
      to 12 months. Triple antithrombotic therapy with OAC plus DAPT of shortest
      feasible duration is warranted, followed by dual antithrombotic therapy of OAC
      and antiplatelet agent, and OAC alone after 12 months. Because of elevated risk
      of hemorrhagic complications, new-generation drug-eluting stents, lower-intensity
      OAC, radial access, and routine use of gastric protection with proton pump
      inhibitors are recommended.

PMID- 27886826
TI  - Antiplatelet and Anticoagulation Therapy in Percutaneous Coronary Intervention.

PMID- 27886828
TI  - Wrist Arthroscopy for Athletic Injuries.
AB  - Management of hand and wrist injuries for athletes often places emphasis on an
      expeditious return to sport. Arthroscopic techniques have the advantage of
      directly visualizing joint derangements and correcting them via a minimally
      invasive approach. This article discusses the evaluation and management of common
      wrist injuries treated with arthroscopy in athletes, including scapholunate and
      lunotriquetral injury, triangular fibrocartilage complex tears, hamatolunate
      impingement, and arthroscopic-assisted reduction of wrist fractures.

PMID- 27886827
TI  - Treating the Football Athlete: Coaches' Perspective from the University of
      Michigan.
AB  - Although football is one of the most popular sports in America, its high injury
      incidence places concern on the injury prevention and safety of its players. This
      article investigates the perspectives of two National Collegiate Athletic
      Association Division 1 football coaches on promoting injury management and player
      safety while maintaining a highly competitive team. Through obtaining their
      coaching philosophy team management topics, effective strategies that contribute
      to a team culture prioritizing player well-being were identified. Interactions of
      football coaches with physicians and medical specialists are explored to
      highlight strengths that can optimize the care and treatment of football
      athletes.

PMID- 27886829
TI  - Finger Injuries in Ball Sports.
AB  - Finger injuries are common in athletes playing in professional ball sports.
      Understanding the intricate anatomy of the digit is necessary to properly
      diagnose and manage finger injuries. Unrecognized or poorly managed finger
      injuries can lead to chronic deformities that can affect an athlete's
      performance. Multiple factors and treatment options should be considered to
      provide the best functional outcome and rapid return to play for an athlete. This
      article discusses the mechanism of injury, diagnosis, treatment, and return-to
      play recommendations for common finger injuries in ball sports.

PMID- 27886830
TI  - Flexor Tendon Pulley Injuries in Rock Climbers.
AB  - Closed pulley ruptures are rare in the general population but occur more
      frequently in rock climbers due to biomechanical demands on the hand. Injuries
      present with pain and swelling over the affected pulley, and patients may feel or
      hear a pop at the time of injury. Sequential pulley ruptures are required for
      clinical bowstringing of the flexor tendons. Ultrasound confirms diagnosis of
      pulley rupture and evaluates degree of displacement of the flexor tendons.
      Isolated pulley ruptures frequently are treated conservatively with early
      functional rehabilitation. Sequential pulley ruptures require surgical
      reconstruction. Most climbers are able to return to their previous activity
      level.

PMID- 27886832
TI  - Thumb Injuries in Athletes.
AB  - Thumb injuries are common in athletes and present a challenging opportunity for
      upper extremity physicians. Common injuries include metacarpal base fractures
      (Bennett and Rolando types), ulnar and radial collateral ligament injuries,
      dislocation of the carpometacarpal and metacarpophalangeal joints, and phalanx
      fractures. This review, although not exhaustive, highlights some of the most
      common thumb injuries in athletes. The treating physician must balance pressure
      from athletes, parents, coaches, and executives to expedite return to play with
      the long-term well-being of the athlete. Operative treatment may expedite return
      to play; however, one must carefully weigh the added risks involved with surgical
      intervention.

PMID- 27886831
TI  - Finger Injuries in Football and Rugby.
AB  - Football and rugby athletes are at increased risk of finger injuries given the
      full-contact nature of these sports. Some players may return to play early with
      protective taping, splinting, and casting. Others require a longer rehabilitation
      period and prolonged time away from the field. The treating hand surgeon must
      weigh the benefits of early return to play for the current season and future
      playing career against the risks of reinjury and long-term morbidity, including
      post-traumatic arthritis and decreased range of motion and strength. Each player
      must be comprehensively assessed and managed with an individualized treatment
      plan.

PMID- 27886834
TI  - Upper Extremity Injuries in Gymnasts.
AB  - Gymnastics is a unique sport, which loads the wrist and arms as weight-bearing
      extremities. Because of the load demands on the wrist in particular, stress
      fractures, physeal injury, and overuse syndromes may be observed. This spectrum
      of injury has been termed "gymnast's wrist," and incorporates such disorders as
      wrist capsulitis, ligamentous tears, triangular fibrocartilage complex tears,
      chondromalacia of the carpus, stress fractures, distal radius physeal arrest, and
      grip lock injury.

PMID- 27886835
TI  - Shoulder Injuries in the Overhead Throwing Athlete.
AB  - The overhead pitching motion is a coordinated sequence of movements that subjects
      the shoulder to extreme forces. The ultimate goal of this complex, dynamic
      activity is to generate high ball velocity and accuracy. In doing so, repetitive
      throwing can cause adaptive and pathologic changes in the thrower's shoulder.
      This article reviews the relevant shoulder anatomy, the kinetic chain, and
      throwing mechanics, as well as common shoulder injuries and surgical options for
      the treating orthopedic surgeon.

PMID- 27886833
TI  - Upper Extremity Injuries in Tennis Players: Diagnosis, Treatment, and Management.
AB  - Upper extremity tennis injuries are most commonly characterized as overuse
      injuries to the wrist, elbow, and shoulder. The complex anatomy of these
      structures and their interaction with biomechanical properties of tennis strokes
      contributes to the diagnostic challenges. A thorough understanding of tennis
      kinetics, in combination with the current literature surrounding diagnostic and
      treatment methods, will improve clinical decision-making.

PMID- 27886836
TI  - Ulnar Neuropathy in Cyclists.
AB  - The form and function of the cyclist exposes the ulnar nerve to both traction and
      compressive forces at both the elbow and wrist. Prevention of ulnar neuropathy
      and treatment of early symptoms include bike fitting, avoidance of excessive or
      prolonged weight-bearing through the hands, and the use of padded gloves. For
      persisting or progressive symptoms, a thorough history and physical examination
      is essential to confirm the diagnosis and to rule out other sites of nerve
      compression. The majority of compression neuropathies in cyclists resolve after
      appropriate rest and conservative treatment; however, should symptoms persist,
      nerve decompression may be indicated.

PMID- 27886837
TI  - Therapy and Rehabilitation for Upper Extremity Injuries in Athletes.
AB  - The approach to rehabilitation of upper extremity injuries in athletes differs
      from traditional rehabilitation protocols. In general, athletes have higher
      functional demands and wish to return to competitive sport in a timely manner.
      Comprehensive rehabilitation must therefore be balanced with a timely and safe
      return to sport. Several rehabilitation programs and adjunctive therapies are
      available to hasten convalescence while minimizing the athlete's risks of
      reinjury. Here, we review techniques for soft tissue mobilization and strength
      training in athletic populations. We also discuss orthotics, taping, and
      alternative therapies used in rehabilitation and evaluate the evidence in support
      of these modalities.

PMID- 27886839
TI  - Medial Elbow Injuries in the Throwing Athlete.
AB  - Medial elbow injuries in the throwing athlete are common and increasing in
      frequency. They occur due to repetitive supraphysiologic forces acting on the
      elbow during the overhead throw. Overuse and inadequate rest are salient risk
      factors for injury. Most athletes improve substantially with rest and
      nonoperative treatment, although some athletes may require surgical intervention
      to return to play. Because of advances in conservative and surgical treatments,
      outcomes after medial elbow injury have improved over time. Currently, most
      athletes are able to return to a high level of play after ulnar collateral
      ligament reconstruction and experience a low rate of complications.

PMID- 27886838
TI  - Biceps and Triceps Ruptures in Athletes.
AB  - Although rare, biceps and triceps tendon ruptures constitute significant injuries
      that can lead to profound disability if left untreated, especially in the
      athletic population. Biceps rupture is more common than triceps rupture, with
      both resulting from a forceful eccentric load. Surgical repair is the treatment
      method of choice for tendinous ruptures in athletes. Nonoperative management is
      rarely indicated in this population and is typically reserved for individuals
      with partial ruptures that quickly regain strength and function. Surgical
      anatomy, evaluation, diagnosis, and surgical management of these injuries are
      covered in this article.

PMID- 27886840
TI  - Elbow Dislocations in Contact Sports.
AB  - Elbow dislocations are more common in athletes than in the general population.
      Simple elbow dislocations should be managed with early range of motion and early
      return to sport, even with high-level contact athletes. Patients with instability
      on examination or with complex elbow dislocations may require surgical
      intervention. Overall, the outcomes after simple elbow dislocations are excellent
      and athletes should be able to return to play without significant limitations.

PMID- 27886841
TI  - Management of Upper Extremity Injury in Divers.
AB  - Modern competitive diving-especially platform diving-applies dramatic stress to
      the upper extremity. Some stress occurs during handstand-style takeoffs, but more
      force is delivered to the hand, wrist, elbow, and shoulder during hands-first
      entry. Hand positions that minimize the amount of splash result in forceful wrist
      extension. This repetitive impact can lead to chronic upper extremity pain and
      acute injuries that require operative intervention. Many divers use taping and
      bracing to prevent or treat this type of injury, but these are only modestly
      effective. Although minor injuries can improve with conservative management,
      carpal fractures and ligamentous injuries often require operative intervention.

PMID- 27886842
TI  - Hand and Wrist Injuries in Golfers and Their Treatment.
AB  - A thorough understanding of the swing phases and mechanisms of injury in golf
      allows accurate diagnosis, treatment, and future prevention of injuries.
      Recommended initial treatment starts with cessation of practice to rest the
      wrist, a splint or orthotic brace, and nonsteroidal antiinflammatory drug
      medication with corticosteroid injection and swing modification. Pisiform
      excision is the best treatment of the most severe chronic cases of pisiform
      ligament complex syndrome. Delayed diagnosis of hook of hamate fracture may lead
      to complications, including flexor tendon rupture. Prompt surgical resection is
      recommended to hasten return to sport and to prevent further complications.

PMID- 27886843
TI  - Expediting Professional Athletes' Return to Competition.
AB  - Return-to-play (RTP) decisions often represent a challenge to physicians caring
      for athletes. The multifaceted and unique nature of each RTP decision makes
      standardization of the decision-making process impossible and demands of the
      physician thoughtful consideration of all competing interests and variables. Such
      difficult medical decisions are further complicated by unique ethical and legal
      considerations. Although no concrete RTP recommendations are available, the
      consensus of experienced team physicians and knowledge of the rules and
      regulations that apply to RTP are helpful guides to treating the various upper
      extremity injuries that occur in elite athletes.

PMID- 27886844
TI  - Hand and Wrist Injuries in Boxing and the Martial Arts.
AB  - Hand and wrist injuries in martial arts are typically a reflection of the combat
      nature of this discipline. In striking sports, the axial load mechanism of injury
      is common and causes fractures and dislocations; in grappling sports, sprain
      injuries and degenerative changes predominate. There is clear evidence to support
      that hand protection reduces the risk of hand injury. Traditional training in
      martial arts on proper technique and target selection in striking sports reduces
      the risk of hand injury, and is an important component of hand and wrist injury
      prevention.

PMID- 27886845
TI  - Optimizing the Treatment of Upper Extremity Injuries in Athletes.

PMID- 27886846
TI  - Are we facing a noncommunicable disease pandemic?
AB  - The global boom in premature mortality and morbidity from noncommunicable
      diseases (NCDs) shares many similarities with pandemics of infectious diseases,
      yet public health professionals have resisted the adoption of this label. It is
      increasingly apparent that NCDs are actually communicable conditions, and
      although the vectors of disease are nontraditional, the pandemic label is apt.
      Arguing for a change in terminology extends beyond pedantry as the move carries
      serious implications for the public health community and the general public.
      Additional resources are unlocked once a disease reaches pandemic proportions
      and, as a long-neglected and underfunded group of conditions, NCDs desperately
      require a renewed sense of focus and political attention. This paper provides
      objections, definitions, and advantages to approaching the leading cause of
      global death through an alternative lens. A novel framework for managing NCDs is
      presented with reference to the traditional influenza pandemic response.

PMID- 27886847
TI  - Autophagy in the respiratory diseases.

PMID- 27886848
TI  - Management of lung cancer with chronic obstructive pulmonary disorder - What are
      the issues?

PMID- 27886850
TI  - Cellular senescence and autophagy in the pathogenesis of chronic obstructive
      pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).
AB  - Aging is associated with impairments in homeostasis. Although aging and
      senescence are not equivalent, the number of senescent cells increases with
      aging. Cellular senescence plays important roles in tissue repair or remodeling,
      as well as embryonic development. Autophagy is a process of lysosomal self
      degradation that maintains a homeostatic balance between the synthesis,
      degradation, and recycling of cellular proteins. Autophagy diminishes with aging;
      additionally, accelerated aging can be attributed to reduced autophagy. Cellular
      senescence has been widely implicated in the pathogenesis of chronic obstructive
      pulmonary disease (COPD), a disease of accelerated lung aging, presumably by
      impairing cell repopulation and by aberrant cytokine secretion in the senescence
      associated secretory phenotype. The possible participation of autophagy in the
      pathogenic sequence of COPD has been extensively explored. Although it has been
      reported that increased autophagy may induce epithelial cell death, an
      insufficient reserve of autophagy can induce cellular senescence in bronchial
      epithelial cells of COPD. Furthermore, advanced age is one of the most important
      risk factors for the development of idiopathic pulmonary fibrosis (IPF). Telomere
      shortening is found in blood leukocytes and alveolar epithelial cells from
      patients with IPF. Accelerated senescence of epithelial cells plays a role in IPF
      pathogenesis by perpetuating abnormal epithelial-mesenchymal interactions.
      Insufficient autophagy may be an underlying mechanism of accelerated epithelial
      cell senescence and myofibroblast differentiation in IPF. Herein, we review the
      molecular mechanisms of cellular senescence and autophagy and summarize the role
      of cellular senescence and autophagy in both COPD and IPF.

PMID- 27886849
TI  - Prevalence and burden of comorbidities in Chronic Obstructive Pulmonary Disease.
AB  - The classical definition of Chronic Obstructive Pulmonary Disease (COPD) as a
      lung condition characterized by irreversible airway obstruction is outdated. The
      systemic involvement in patients with COPD, as well as the interactions between
      COPD and its comorbidities, justify the description of chronic systemic
      inflammatory syndrome. The pathogenesis of COPD is closely linked with aging, as
      well as with cardiovascular, endocrine, musculoskeletal, renal, and
      gastrointestinal pathologies, decreasing the quality of life of patients with
      COPD and, furthermore, complicating the management of the disease. The most
      frequently described comorbidities include skeletal muscle wasting, cachexia
      (loss of fat-free mass), lung cancer (small cell or non-small cell), pulmonary
      hypertension, ischemic heart disease, hyperlipidemia, congestive heart failure,
      normocytic anemia, diabetes, metabolic syndrome, osteoporosis, obstructive sleep
      apnea, depression, and arthritis. These complex interactions are based on chronic
      low-grade systemic inflammation, chronic hypoxia, and multiple common
      predisposing factors, and are currently under intense research. This review
      article is an overview of the comorbidities of COPD, as well as their interaction
      and influence on mutual disease progression, prognosis, and quality of life.

PMID- 27886851
TI  - The role of necroptosis in pulmonary diseases.
AB  - By regulating the cell number and eliminating harmful cells, programmed cell
      death plays a critical role in development, homeostasis, and disease. While
      apoptosis is a recognized form of programmed cell death, necrosis was considered
      a type of uncontrolled cell death induced by extreme physical or chemical stress.
      However, recent studies have revealed the existence of a genetically programmed
      and regulated form of necrosis, termed necroptosis. Necroptosis is defined as
      necrotic cell death that is dependent on receptor-interacting protein kinase 3
      (RIPK3). RIPK3, receptor-interacting protein kinase 1 (RIPK1), and a mixed
      lineage kinase domain-like protein (MLKL) form a multiprotein complex called a
      necrosome. Although necroptosis generally provides a cell-autonomous host
      defense, on the other hand, cell rupture caused by necroptosis induces
      inflammation through the release of damage-associated molecular patterns, such as
      mitochondrial DNA, HMGB1, and IL-1. Previously, necroptosis was considered an
      alternative to apoptosis, but it is becoming increasingly clear that necroptosis
      itself is relevant to clinical disease, independent of apoptosis. According to
      some recent studies, autophagy, a cellular process for organelle and protein
      turnover, regulates necroptosis. This review outlines the principal components of
      necroptosis and provides an overview of the emerging importance of necroptosis in
      the pathogenesis of pulmonary disease, including chronic obstructive pulmonary
      disease, lung cancer, infection, and sepsis. We also discuss the molecular
      relationship between necroptosis and autophagy. Strategies targeting necroptosis
      may yield novel therapies for pulmonary diseases.

PMID- 27886852
TI  - "Cold air" and/or "talking" as cough triggers, a sign for the diagnosis of cough
      variant asthma.
AB  - BACKGROUND: Fractional exhaled nitric oxide (FeNO) is considered an alternative
      marker of eosinophilic airway inflammation and is sometimes incorporated in the
      diagnosis of asthma. However, many patients with cough variant asthma (CVA)
      demonstrate an FeNO in the normal range. Therefore, additional information is
      needed to confirm the diagnosis of CVA, particularly in patients with low FeNO
      levels. We aimed to investigate the feasibility of using cough triggers to help
      diagnose CVA. METHODS: We studied 163 patients presenting with prolonged/chronic
      cough alone (including 104 CVA patients) who underwent FeNO measurements and an
      airway responsiveness test, and answered a questionnaire listing 18 cough
      triggers. The sensitivity and specificity of FeNO levels and cough triggers for
      the diagnosis of CVA were determined. RESULTS: CVA patients showed higher FeNO
      levels than non-CVA patients. When the cut-off value of FeNO levels for the
      diagnosis of CVA was set at 22ppb, its sensitivity was 57%. CVA patients more
      frequently responded to "cold air" and "talking" as cough triggers than non-CVA
      patients. When the analysis was confined to those with a low FeNO (<22ppb) group,
      the sensitivity and positive predictive values of "cold air" and "talking" for
      the diagnosis of CVA were 36% and 70% for "cold air", and 44% and 74% for
      "talking", respectively. Their specificity was 81%. "Cold air" was associated
      with airway hyperresponsiveness in all patients with an emphasis on those with
      low FeNO levels. CONCLUSION: "Cold air" and/or "talking" as cough triggers could
      be signs for the diagnosis of CVA, particularly when FeNO levels are low.

PMID- 27886854
TI  - Efficacy and safety of indacaterol/glycopyrronium in Japanese patients with COPD:
      Pooled analysis of SHINE and ARISE.
AB  - BACKGROUND: To better evaluate the efficacy and safety of the
      indacaterol/glycopyrronium (IND/GLY) fixed-dose combination versus tiotropium in
      Japanese patients, a pooled data analysis was conducted from the SHINE and ARISE
      studies, which were part of the IND/GLY clinical trial program. METHODS: Japanese
      patients with moderate-to-severe COPD were included in the analysis. Efficacy in
      terms of pre-dose forced expiratory volume in one second (FEV1) at Week 12 and
      Week 24/26 (ARISE/SHINE) and FEV1 at 30min and 60min post-dose at Day 1, Week 12,
      and Week 24/26 was evaluated. Health status using the St. George's Respiratory
      Questionnaire (SGRQ) score, rescue medication use (number of puffs/day), safety,
      and tolerability were also assessed. RESULTS: In total, 340 patients (IND/GLY,
      n=161; IND, n=41; GLY, n=40; tiotropium, n=79; and placebo, n=19) were included
      in the analysis that focused on comparing IND/GLY versus tiotropium since they
      were included in both studies. At Week 12 and Week 24/26, pre-dose FEV1 was
      significantly improved with IND/GLY compared with tiotropium (treatment
      differences=70mL and 80mL, respectively; both P<=0.001). FEV1 at 30min and 60min
      post-dose, the SGRQ total score, and rescue medication use were more
      statistically significant with IND/GLY than with tiotropium for all assessed time
      points. The overall incidence of adverse events (AEs) and serious AEs was similar
      between the IND/GLY- and tiotropium-treated groups. CONCLUSIONS: Compared to
      tiotropium, IND/GLY provided significant improvements in lung function, health
      status, and rescue medication use, while having a good safety profile in Japanese
      patients with moderate-to-severe COPD.

PMID- 27886853
TI  - Airway remodeling associated with cough hypersensitivity as a consequence of
      persistent cough: An experimental study.
AB  - BACKGROUND: Chronic cough involves airway remodeling associated with cough reflex
      hypersensitivity. Whether cough itself induces these features remains unknown.
      METHODS: Guinea pigs were assigned to receive treatment with citric acid (CA),
      saline (SA), or CA+dextromethorphan (DEX). All animals were exposed to 0.5M CA on
      days 1 and 22. On days 4-20, the CA and CA+DEX groups were exposed to CA, and the
      SA group to saline thrice weekly, during which the CA+DEX group was administered
      DEX pretreatment to inhibit cough. The number of coughs was counted during each
      10-min CA or SA exposure. Terbutaline premedication was started to prevent
      bronchoconstriction. Bronchoalveolar lavage and pathology were examined on day
      25. Average cough number for 10 CA exposures was examined as "cough index" in the
      CA group, which was divided into frequent (cough index>5) and infrequent (<5)
      cough subgroups for lavage and pathology analysis. RESULTS: The number of coughs
      significantly increased in the CA group from day 13 onwards. In the CA+DEX and SA
      groups, the number of coughs did not differ between days 1 and 22, while average
      number of coughs during days 4-20 was significantly lower than at days 1 and 22.
      Bronchoalveolar cell profiles were similar among the four groups. The smooth
      muscle area of small airways was significantly greater in the frequent-cough
      subgroup than in the other groups (in which it was similar), and highly
      correlated with cough index in CA group. CONCLUSION: Repeated cough induces
      airway smooth muscle remodeling associated with cough reflex hypersensitivity.

PMID- 27886855
TI  - Electrically induced mechanomyograms reflect inspiratory muscle strength in young
      or elderly subjects.
AB  - BACKGROUND: Respiratory muscle strength has been used as a tool for evaluating
      respiratory rehabilitation in chronic obstructive pulmonary disease. However,
      mouth pressure measurement evaluated by maximum expiratory mouth pressure (PEmax)
      or inspiratory mouth pressure (PImax) offers an indirect method for measuring
      respiratory muscle strength. We demonstrated the evaluation of diaphragm
      contractility using a mechanomyogram (MMG), which is the mechanical signal
      generated by the motion of the diaphragm induced by the electric stimulation of
      the phrenic nerve. METHODS: Study participants were 21 young and 20 elderly
      subjects with no symptoms of respiratory disease. The elderly subjects were
      divided into non-smoker or smoker groups. The smoker group was defined as
      subjects having a Brinkman Index of greater than 300. We measured basic
      spirometric parameters, mouth pressure (PEmax, PImax), and diaphragmatic MMG.
      RESULTS: Diaphragmatic MMG showed more clear contrast between young subjects and
      elderly non-smoker or smoker subjects than the conventional method for
      respiratory muscle contraction (PEmax, PImax). In addition, the diaphragmatic MMG
      strongly correlated with inspiratory muscle strength. CONCLUSIONS: Diaphragmatic
      MMG may reflect diaphragmatic contractility more directly and sensitively than
      the conventional method.

PMID- 27886856
TI  - A retrospective cohort study of outcome in systemic sclerosis-associated
      interstitial lung disease.
AB  - BACKGROUND: The relationship between the histological pattern and survival in
      systemic sclerosis-associated interstitial lung disease (SSc-ILD) is unclear. In
      patients with SSc-ILD, we investigated whether the clinical data obtained by non
      invasive examinations could be used for prognostic evaluation, and attempted to
      clarify whether complicating acute exacerbation (AE) and the selection of
      pharmacological therapy were associated with survival. METHODS: Thirty-five
      patients with SSc-ILD, who had not been diagnosed by surgical lung biopsy were
      analyzed, retrospectively. The HRCT findings were evaluated by 2 radiologists and
      classified into "CT-UIP" or "CT-inconsistent with UIP" patterns based on whole
      lung interpretations. HRCT scores were calculated based on the extent of
      abnormality evidenced by HRCT. The log-rank test was used to determine variables,
      including clinical parameters and histories. RESULTS: Twelve (34%) of the 35
      patients died during a median follow-up period of approximately 7.9 years. The
      log-rank test showed that a higher mortality was associated with higher age, a CT
      UIP pattern, a higher score for ground-glass attenuation with traction
      bronchiectasis on HRCT, and complicating AE, whereas a lower mortality was
      significantly associated with the use of immunosuppressants. A CT-UIP pattern was
      significantly associated with a higher incidence of later AE. CONCLUSION:
      Treatment with immunosuppressants was associated with a longer survival, and
      complicating AE is a predictor of shortened survival in SSc-ILD patients. Among
      the clinical parameters determined by non-invasive examinations, a CT-UIP pattern
      and the extent of fibrotic lesions on HRCT, but not a histological pattern of
      UIP, may be predictors of shortened survival.

PMID- 27886857
TI  - Factors associated with positive inhalation provocation test results in subjects
      suspected of having chronic bird-related hypersensitivity pneumonitis.
AB  - BACKGROUND: Chronic bird-related hypersensitivity pneumonitis (BRHP) is often
      misdiagnosed as other interstitial lung diseases. While the utility of the
      inhalation provocation test (IPT) has been reported, the test is not commonly
      performed. In this study, we aimed to identify significant clinical variables
      associated with positive inhalation provocation test results in subjects
      suspected of having chronic BRHP. This would help clinicians decide whether to
      perform IPT in patients suspected of having chronic BRHP in real-life practice.
      METHODS: We retrospectively evaluated 107 patients who underwent the IPT for
      suspected chronic BRHP. We used the IPT as the gold standard diagnostic tool for
      chronic BRHP. RESULTS: Specific antibodies against pigeon dropping extract were
      documented in 52% of the IPT-positive patients but also in 38% of the IPT
      negative patients (p=0.172). By using the logistic regression model, three
      significant predictors of IPT results were identified as follows: (1) a history
      of raising birds (odds ratio [OR] 3.112), (2) exposure to birds from the
      surrounding environment (OR 7.321), (3) white blood cell count (*102/MUl; OR
      0.959). CONCLUSIONS: This study demonstrates that current or past exposure to
      avian antigens is a positive predictor of positive IPT results in patients
      suspected of having chronic BRHP.

PMID- 27886859
TI  - Tolerability and efficacy of afatinib at a low starting dosage in 10 elderly or
      low performance status patients with advanced refractory non-small-cell lung
      cancer.
AB  - BACKGROUND: Whether a full dosage of afatinib is tolerable and effective for
      elderly or low performance status (PS) patients with advanced refractory non
      small-cell lung cancer (NSCLC) is unclear. METHODS: We retrospectively evaluated
      the tolerability and efficacy of afatinib in 10 patients (the majority elderly)
      with a low PS score (2 or 3), who had advanced refractory adenocarcinoma and were
      carrying active epidermal growth factor receptor mutations. Afatinib was
      administered at a starting dosage of 20 or 30mg/day, followed by 10mg increases
      in dose up to a maximum dosage of 40mg/day. RESULTS: The median patient age was
      76 years and 50% of the patients had a PS of 3. The patients had previously been
      treated with gefitinib and/or erlotinib, with a median number of three
      chemotherapy regimens. All the patients received at least 30mg/day of afatinib.
      Eight patients did not receive the 40mg/day dosage because of patient refusal due
      to grade 2 diarrhea (n=6) or the judgment of the doctor (n=2). One patient
      discontinued the treatment because of drug-induced interstitial lung disease. The
      most frequent adverse event was grade 2 diarrhea. The objective response rate was
      11% and the PS score of five cases improved after afatinib therapy. The median
      progression-free survival and overall survival periods were 3.6 months and 5.8
      months, respectively. CONCLUSIONS: A low starting dosage of afatinib might enable
      elderly or low PS patients with advanced refractory NSCLC to receive this drug as
      salvage therapy.

PMID- 27886858
TI  - Clinical analysis of patients treated with afatinib for advanced non-small cell
      lung cancer: A Nagano Lung Cancer Research Group observational study.
AB  - BACKGROUND: Afatinib has been available in Japan for the treatment of epidermal
      growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) since
      May 2014. We conducted an observational study in patients treated with afatinib
      in Nagano prefecture, focusing on response and associated toxicities. METHODS: We
      analyzed the clinical records of NSCLC patients treated with afatinib between May
      2014 and February 2015. RESULTS: The records of a total of 73 patients (27 men,
      46 women) with a median age of 69 years (range: 42-85 years) were analyzed.
      Afatinib was administered to 11 patients as a first-line therapy, but it was
      predominantly administered as a fifth-line or beyond therapy (32 cases, 43.8%).
      The overall response rates for afatinib as a first-line therapy and beyond second
      line therapy were 80% (95% confidence interval [CI]: 55.2-100.0%) and 27.1% (95%
      CI: 14.5-39.7%), respectively. The main toxicities grade >3 included diarrhea
      (8.2%), skin rash (6.8%), nausea (6.8%), and appetite loss (6.8%). A low body
      surface area (BSA) (<1.5m2) was significantly associated with a higher frequency
      of diarrhea grade >2, compared with a higher BSA (>= 1.5m2). Forty-eight patients
      (63.0%) were treated without a dose reduction of afatinib. CONCLUSIONS: Although
      the survival benefit with afatinib remains unclear, our observational analysis
      demonstrated the feasibility of using afatinib for EGFR-mutated NSCLC in clinical
      practice. In particular, a relatively high level of drug delivery is possible. In
      addition, a lower BSA may be a predictor of diarrhea in patients treated with
      afatinib.

PMID- 27886860
TI  - The predictive value of endobronchial ultrasonography with a guide sheath in the
      diagnosis of the histologic subtypes of lung cancer.
AB  - BACKGROUND: Recent studies have shown differential response to chemotherapy among
      the subtypes of non-small cell lung carcinoma (NSCLC). Therefore, to accurately
      differentiate between the types of lung cancer is of paramount importance.
      Transbronchial biopsy using endobronchial ultrasonography with a guide sheath
      (EBUS-GS) is a promising method for the diagnosis of NSCLC. The purpose of this
      study was to evaluate the consistency between the types of lung cancer
      histologically diagnosed by bronchial biopsy or cytologically by EBUS-GS, and the
      final diagnosis of the resected specimen. METHODS: A retrospective analysis was
      performed on 203 patients having primary lung cancers diagnosed by EBUS-GS, who
      subsequently underwent curative pulmonary resection at the Hokkaido University
      Hospital between July 2003 and December 2011. In the present study, non-small
      cell carcinoma was defined as non-squamous cell carcinoma, and squamous cell
      carcinoma (Sq) was excluded. RESULTS: Of the 40 cases diagnosed as Sq by EBUS-GS,
      37 cases were diagnosed as Sq, and 3 cases were diagnosed as non-Sq after
      surgical resection. Of the 159 cases diagnosed as non-Sq by EBUS-GS, 151 cases
      were diagnosed as non-Sq, 6 as Sq, and 2 as small cell carcinoma after surgical
      resection. These results showed that the positive predictive value of EBUS-GS in
      the diagnosis of Sq was 93%, and its positive predictive value in diagnosing non
      Sq was 95%. CONCLUSIONS: The pathological subtyping of NSCLC using small tissue
      and cytology samples obtained by EBUS-GS appears to effectively distinguish
      between Sq and non-Sq and is therefore considered useful in making a treatment
      decision.

PMID- 27886862
TI  - Advancing tuberculosis screening in Japan: Historical considerations and the way
      forward.

PMID- 27886863
TI  - Analysis of scrub typhus involvement of the lung by bronchoalveolar lavage: A
      case report.

PMID- 27886861
TI  - Applicability of the Japanese equation for estimating glomerular filtration rate
      in patients with advanced-stage thoracic cancer.
AB  - BACKGROUND: The 24-h creatinine clearance (24-h Ccr) and the Cockcroft-Gault
      equation (CG) are commonly used as markers of renal function in clinical
      practice. However, the utility of the Japanese equation for estimating glomerular
      filtration rate (eGFR) in cancer patients has not yet been evaluated. The aim of
      this cross-sectional study was to investigate the extent and correlating factors
      for differences between eGFR and both 24-h Ccr and CG in advanced-stage thoracic
      cancer patients. METHODS: eGFR, 24-h Ccr, and CG were calculated in 90 patients
      with thoracic malignancies. We evaluated how these three parameters are affected
      by clinical factors, including age, body surface area, serum creatinine
      concentration, and body mass index. RESULTS: eGFR and CG were significantly
      correlated with 24-h Ccr (r=0.64, p<0.001 and; r=0.67, p<0.001, respectively).
      However, the median value derived from eGFR was higher than the median 24-h Ccr
      and the CG value (74.0, 65.2, and 63.9mL/min, respectively). Age had a
      significant positive correlation with the differences between eGFR and both 24-h
      Ccr and CG value (r=0.30, p=0.005 and; r=0.47, p<0.001, respectively). The
      differences between eGFR and the other two parameters were significantly higher
      in older patients (age>=70 years) than in younger patients (age<70 years)
      (p=0.023, p<0.001, respectively). CONCLUSIONS: eGFR is likely to overestimate the
      renal function of elderly cancer patients. A modified equation for evaluating the
      renal function of Japanese older patients might be needed.

PMID- 27886864
TI  - An autopsy case of refractory pulmonary hypertension with sarcoidosis.
AB  - A 63-year-old man with sarcoidosis-associated pulmonary hypertension (SAPH) died
      suddenly of decompensated right heart failure. At autopsy, microscopy showed
      subpleural and interlobular fibrosis in both upper lobes, with marked broncho
      bronchiolectasis, as well as bronchovascular bundle fibrosis and fibrotic
      organization in alveolar lumens, which are consistent with pulmonary sarcoidosis.
      Intimal fibrosis and medial hypertrophy were noted in the proximal elastic to
      distal muscular pulmonary arteries (Heath-Edwards, grades II-III) within
      intensive fibrotic lesions. Additionally, diffuse alveolar capillary
      multiplication (DACM) was present in macroscopically normal lung parenchymal
      lesions, associated with wall muscularization. In this case, muscularization of
      capillaries may have been induced by hypoxemia and hypoxic pulmonary
      vasoconstriction, resulting in pulmonary hypertension.

PMID- 27886866
TI  - Corrigendum to "The effect of different drugs on the preparation and biological
      outcomes of plasma rich in growth factors" [Ann. Anat. 196 (2014) 423-429].

PMID- 27886865
TI  - Two cases of pseudo-achalasia with lung cancer: Case report and short literature
      review.
AB  - Pseudo-achalasia with lung cancer is a rare complication. We present 2 cases of
      pseudo-achalasia with lung cancer and summarize previous reports. The previous
      reports suggested that lung cancer can be complicated with pseudo-achalasia
      caused by paraneoplastic neurological syndromes rather than direct invasion of
      the tumor cells to the lower esophageal sphincter, irrespective of the histology
      of the lung cancer; this can strongly influence the performance status. Treatment
      for pseudo-achalasia improves not only the symptoms, but also the performance
      status. Therefore, pseudo-achalasia should be considered when lung cancer
      patients present with dysphagia without other known causes.

PMID- 27886867
TI  - Is It Time to Retire Santa Claus?

PMID- 27886868
TI  - Pilot Evaluation of the Informant AD8 as a Case-Finding Instrument for Cognitive
      Impairment in General Practitioner Clinics of Singapore: A Brief Report.
AB  - BACKGROUND: Case-finding services using a composite total risk score (TRS) and
      the informant AD8 have been previously recommended to detect cognitive impairment
      (CI) in government subsidized primary health care centers of Singapore (ie,
      polyclinics). OBJECTIVE: We compared the feasibility of implementing the services
      recommended for government-subsidized primary health care in private, primary
      health care service providers such as general practitioner (GP) clinics. METHOD:
      123 patients >=60 years of age were recruited from 2 GP clinics within Singapore.
      Trained research personnel administered the AD8 to informants. Patients of the
      present study were compared against a random sample of 123 patients selected from
      polyclinics. RESULTS: Significantly higher positive screening rates (AD8 >=3)
      were found among patients in polyclinics than GP clinics (P < .001). Patients
      attending polyclinics reported more comorbid medical issues such as subjective
      cognitive complaint (P < .001) and heart disease (P < .001). The TRS of patients
      attending polyclinics was significantly higher than those attending GP clinics (P
      < .001), indicating a higher proportion of patients at risk of CI in polyclinics.
      Therefore, patients attending polyclinics were found to have higher AD8 scores
      compared with patients in GP clinics (P < .001). CONCLUSION: Compared with GP
      clinics, polyclinics may be more suited to provide case-finding services for the
      detection of CI in primary health care.

PMID- 27886870
TI  - Interventions for the Treatment of Pain in Nursing Home Residents: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: More than one-half of nursing home residents experience a complex mix
      of pain. Despite this, assessment and treatment of pain remain inadequate.
      METHODS: Using techniques of the Cochrane Collaboration and Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we assessed
      efficacy of interventions aimed at reducing chronic pain in nursing home
      residents >65 years of age. We searched for controlled trials comparing and
      measuring pain interventions using standardized pain scales. Two reviewers
      independently selected included studies, abstracted data, and assessed risk of
      bias. We performed meta-analyses calculating standardized mean differences (SMDs)
      using random effect models. RESULTS: Fourteen trials (n = 2293) were included in
      the meta-analysis: 7 reported nonanalgesic treatments, 4 reported analgesic
      treatments, 5 reported system modifications, and 2 reported educational
      interventions. A variety of pain scales were used, reporting outcome measures
      from 1 week to 1 year. Pooled results at trial completion revealed a
      statistically significant small treatment effect [SMD -0.33, 95% confidence
      interval (CI) -0.51, -0.14]. Further subgroup analysis revealed that residents
      receiving analgesic interventions benefited most (SMD -0.65, 95% CI -1.07, 
      0.23), followed by those receiving educational interventions (SMD -0.40, 95% CI 
      0.59, -0.21), and those receiving system modification interventions (SMD -0.26,
      95% CI -0.51, -0.02). CONCLUSIONS: Nonanalgesic treatment and control groups
      showed no statistical differences. Our findings suggest that analgesics are the
      most effective pain intervention and should be considered first-line therapy.
      Caution should be used in interpreting findings as few trials were included, risk
      of bias was variable, sample sizes were small, and pooled treatment effects were
      small to moderate.

PMID- 27886869
TI  - Frailty and the Prediction of Negative Health Outcomes: A Meta-Analysis.
AB  - INTRODUCTION: Frailty is one of the most important concerns regarding our aging
      population. Evidence grows that the syndrome is linked to several important
      health outcomes. A general overview of frailty concepts and a comprehensive meta
      analysis of their relation with negative health outcomes still lacks in
      literature, making it difficult for health care professionals and researchers to
      recognize frailty and the related health risks on the one hand and on the other
      hand to appropriately follow up the frailty process and take substantiated
      action. Therefore, this study aims to give an overview of the predictive value of
      the main frailty concepts for negative health outcomes in community-dwelling
      older adults. METHODS: This review and meta-analysis assembles prospective
      studies regarding the relation between frailty and any potential health outcome.
      Frailty instruments were subdivided into frailty concepts, so as to make
      comprehensive comparisons. Odds ratios (ORs), hazard ratios (HRs), and relative
      risk (RR) scores were extracted from the studies, and meta-analyses were
      conducted in OpenMeta Analyst software. RESULTS: In total, 31 articles retrieved
      from PubMed, Web of Knowledge, and PsycInfo provided sufficient information for
      the systematic review and meta-analysis. Overall, (pre)frailty increased the
      likelihood for developing negative health outcomes; for example, premature
      mortality (OR 2.34 [1.77-3.09]; HR/RR 1.83 [1.68-1.98]), hospitalization (OR 1.82
      [1.53-2.15]; HR/RR 1.18 [1.10-1.28]), or the development of disabilities in basic
      activities of daily living (OR 2.05 [1.73-2.44]); HR/RR 1.62 [1.50-1.76]).
      CONCLUSION: Overall, frailty increases the risk for developing any discussed
      negative health outcome, with a 1.8- to 2.3-fold risk for mortality; a 1.6- to
      2.0-fold risk for loss of activities of daily living; 1.2- to 1.8-fold risk for
      hospitalization; 1.5- to 2.6-fold risk for physical limitation; and a 1.2- to 2.8
      fold risk for falls and fractures. The analyses presented in this study can be
      used as a guideline for the prediction of negative outcomes according to the
      frailty concept used, as well as to estimate the time frame within which these
      events can be expected to occur.

PMID- 27886871
TI  - Update on New Imaging Techniques for Trauma.
AB  - Computed tomography (CT) and MRI are complementary imaging modalities for the
      evaluation of the traumatic spine. Osseous delineation is best assessed with CT,
      whereas MRI gives superb soft tissue description. Awareness of the strengths and
      pitfalls of each modality is critical in the accurate interpretation of images.
      Advances in MR imaging of the spine, particularly of the spinal cord, provide
      glimpses into to the pathobiological mechanism of spinal cord injury. Innovative
      techniques relay microstructural information about the integrity of the axons and
      myelin sheaths. In addition to clinical status, imaging features may be helpful
      in prognostication and in monitoring therapeutic interventions.

PMID- 27886872
TI  - Pediatric Thoracolumbar Spine Trauma.
AB  - This article reviews thoracolumbar injury patterns that may be seen in children.
      Although much of the management of these injuries has been extrapolated from the
      adult literature, unique surgical and nonsurgical considerations in treating
      children with thoracolumbar spine fractures are discussed. In conclusion, most
      children achieve satisfactory outcomes in long-term follow-up after healing.

PMID- 27886873
TI  - Treatment of Odontoid Fractures in the Aging Population.
AB  - Odontoid fractures are the most common cervical fracture type among the elderly
      population. Several treatment options exist for these patients, ranging from
      immobilization with a semirigid orthosis to surgical arthrodesis. This report
      reviews the key points in the management of odontoid fractures in the aged
      patient, including diagnosis, the various forms of conservative therapies, and
      the options for surgical intervention.

PMID- 27886874
TI  - Treatment of Facet Injuries in the Cervical Spine.
AB  - Facet injuries are common in the cervical spine. Many classification systems over
      the years have characterized the heterogeneity of these injuries. For unilateral
      facet fractures with minimal displacement and no neurological deficit, there is
      mounting evidence that better radiographic and clinical outcomes may be achieved
      with surgical treatment. Anterior and posterior approaches can both be utilized
      successfully for the surgical management of facet injuries. The anterior approach
      is well tolerated, allows one to address a disc herniation, and provides a high
      union rate with good sagittal alignment. The posterior approach allows for easier
      open reduction and biomechanically superior fixation.

PMID- 27886875
TI  - The Role of a Miniopen Thoracoscopic-assisted Approach in the Management of Burst
      Fractures Involving the Thoracolumbar Junction.
AB  - Thoracoscopic spinal surgery is a minimally invasive open endoscopic approach to
      the anterior thoracolumbar spine for decompression and stabilization. It offers
      an alternative to open thoracotomy for thoracolumbar burst fractures, anterior
      spinal cord decompression, and spinal reconstruction with interbody and
      anterolateral plate instrumentation for restoration of biomechanical stability
      and alignment. Posterior instrumentation may not sufficiently stabilize a
      significantly disrupted anterior load-bearing spinal column, and the high access
      morbidity of open procedures is of significant concern. The adoption by spine
      surgeons of minimally invasive thoracoscopic techniques used by thoracic surgeons
      has expanded to include treatment of most anterior thoracolumbar disorders.

PMID- 27886876
TI  - Complications in the Management of Patients with Spine Trauma.
AB  - More than 50% of patients diagnosed with acute, traumatic spinal cord injury will
      experience at least 1 complication during their hospitalization. Age, severity of
      neurological injury, concurrent traumatic brain injury, comorbid illness, and
      mechanism of injury are all associated with increasing risk of complication. More
      than 75% of complications will occur within 2 weeks of injury. The complications
      associated with SCI carry a significant risk of morbidity and mortality; their
      early identification and management is critical in the care of the SCI patient.

PMID- 27886877
TI  - Minimally Invasive Treatment of Spine Trauma.
AB  - The role for minimally invasive surgery (MIS) continues to expand in the
      management of spinal pathology. In the setting of trauma, operative techniques
      that can minimize morbidity without compromising clinical efficacy have
      significant value. MIS techniques are associated with decreased intraoperative
      blood loss, operative time, and morbidity, while providing patients with
      comparable outcomes when compared with conventional open procedures. MIS
      interventions further enable earlier mobilization, decreased hospital stay,
      decreased pain, and an earlier return to baseline function when compared with
      traditional techniques. This article reviews patient selection and select MIS
      techniques for those who have suffered traumatic spinal injury.

PMID- 27886878
TI  - Return to Play for Athletes.
AB  - Sports-related activities are associated with a variety of spinal injuries. Spine
      surgeons must be able to determine an athlete's readiness to return to play. Most
      spine surgeons agree that an athlete should be neurologically intact, be pain
      free, be at full strength, and have full range of motion before returning to
      full, unrestricted athletic activity. Certain spine injuries such as stingers may
      allow for return to play nearly immediately; whereas, other clinical entities
      such as spear tackler's spine are considered absolute contraindications to return
      to play.

PMID- 27886879
TI  - Thoracolumbar Trauma Classification.
AB  - Useful thoracolumbar injury classifications allow for meaningful and concise
      communication between surgeons, trainees, and researchers. Although many have
      been proposed, none have been able to obtain universal acceptance. Historically,
      classifications focused only on the osseous injuries; more recent classifications
      focused on the injury morphology and other critical determinants of treatment,
      including the posterior ligamentous complex integrity and the patient's
      neurologic status. This review details the important historic classifications and
      reviews more contemporary thoracolumbar injury classifications, such as the
      Thoracolumbar Injury Classification System and the AOSpine Thoracolumbar Injury
      Classification System.

PMID- 27886880
TI  - Timing of Surgery After Spinal Cord Injury.
AB  - Although timing for surgical intervention after spinal cord injury remains
      controversial, there is accumulating evidence suggesting that early surgery may
      improve neurologic outcomes, particularly with incomplete spinal cord injury, and
      may reduce non-neurologic complications and health care resource utilization.
      Moreover, even in patients with complete spinal cord injury, minor improvement in
      neurologic function can lead to significant changes in quality of life. This
      article reviews the experimental and clinical data examining surgical timing
      after spinal cord injury.

PMID- 27886881
TI  - Central Cord Syndrome.
AB  - Central cord syndrome is a common spinal cord injury. The purpose of this review
      article is to provide an overview of the anatomy, pathophysiology, prognosis, and
      management of this disorder.

PMID- 27886882
TI  - Pharmacologic Management of Acute Spinal Cord Injury.
AB  - Spinal cord injury is a serious global public health problem that often leaves
      patients with devastating permanent disabilities. Although advances in supportive
      care have improved outcome in recent decades, there remains great need for a safe
      and efficacious medical treatment that improves neurologic outcome. This article
      reviews pharmacologic treatments evaluated or in the process of development in
      humans. Cellular transplantation strategies are briefly reviewed especially where
      they have been evaluated with pharmacologic treatments. There is great hope that
      one or more of these new therapeutics will be successfully translated and improve
      the neurologic recovery of patients in the near future.

PMID- 27886883
TI  - Restorative Treatments for Spinal Cord Injury.
AB  - Spinal cord injury remains an incurable disease with an enormous impact
      functionally, financially, and emotionally on affected individuals and their
      families. Current treatment modalities are focused on minimizing secondary injury
      and maximizing residual function via rehabilitation. In this article, the authors
      discuss ambitious advancements under investigation aimed at restoring function.
      These promising experimental treatments focus on neuroprotection with hypothermia
      and pharmacologic therapies, regeneration via cell transplantation, and rewiring
      with electrical stimulation.

PMID- 27886884
TI  - Classification and Management of Pediatric Craniocervical Injuries.
AB  - This article addresses the key features, clinical presentation, patterns of
      injury, indicated workup, and radiographic findings associated with
      craniocervical injuries in the pediatric population. It discusses nonsurgical and
      surgical management of pediatric cervical spine trauma, addressing when each is
      indicated, and the various techniques available to the pediatric neurosurgeon.

PMID- 27886885
TI  - Classification and Management of Pediatric Subaxial Cervical Spine Injuries.
AB  - Appropriate management of subaxial spine injury in children requires an
      appreciation for the differences in anatomy, biomechanics, injury patterns, and
      treatment options compared with adult patients. Increased flexibility, weak neck
      muscles, and cranial disproportion predispose younger children to upper cervical
      injuries and spinal cord injury without radiographic abnormality. A majority of
      subaxial cervical spine injuries can be treated nonoperatively. Surgical
      instrumentation options for children have significantly increased in recent
      years. Future studies of outcomes for children with subaxial cervical spine
      injury should focus on injury classification and standardized outcome measures to
      ensure continued improvement in quality of care for this patient population.

PMID- 27886886
TI  - Adult and Pediatric Spine Trauma.

PMID- 27886887
TI  - New Treatments for Nonarteritic Anterior Ischemic Optic Neuropathy.
AB  - Despite increasing knowledge about the risk factors and clinical findings of
      nonarteritic anterior ischemic optic neuropathy (NAION), the treatment of this
      optic neuropathy has remained limited and without clear evidence-based benefit.
      Historical treatments of NAION are reviewed, beginning with the Ischemic Optic
      Neuropathy Decompression Trial. More recent treatments are placed within the
      historical context and illustrate the need for evidence-based therapy for
      ischemic optic neuropathy.

PMID- 27886888
TI  - Imaging of Oculomotor (Third) Cranial Nerve Palsy.
AB  - When evaluating a patient with an oculomotor cranial nerve palsy it may be
      unclear which neuroimaging modality is optimal; MRI, MR angiography, computed
      tomography, computed tomography angiography, or intraarterial digital subtraction
      angiography. We discuss the clinical guidelines in the evaluation of such
      patients and review neuroimaging techniques, outlining the advantages and
      disadvantages of each.

PMID- 27886889
TI  - Update on Ocular Myasthenia Gravis.
AB  - Ocular myasthenia gravis (OMG) is a localized form of myasthenia gravis in which
      autoantibodies directed against acetylcholine receptors block or destroy these
      receptors at the postsynaptic neuromuscular junction. The hallmark of OMG is a
      history of painless weakness or fatigability of the extraocular muscles and
      ptosis with normal pupillary function and visual acuity. Clinical, laboratory,
      electrophysiologic, and pharmacologic tests are available for diagnosis.
      Treatment can begin with symptom management; there is no cure. Prognosis is
      improved by use of immunomodulators. Despite advances in treatment, research is
      needed, especially in the areas of surgical intervention and medical therapy
      based on risk stratification.

PMID- 27886890
TI  - Orbital Disease in Neuro-Ophthalmology.
AB  - Many abnormalities of the orbit present with neuro-ophthalmic findings, such as
      impaired ocular motility or alignment, and sensory changes, including optic
      neuropathy. Comprehensive coverage of all orbital diseases is beyond the scope of
      this article. This review focuses on diagnosis and management of the most common
      and the most vision- or life-threatening orbital conditions as well as more
      recently discovered entities and points of active controversy. These conditions
      include orbital trauma, vascular disease, inflammatory and infectious diseases,
      and neoplasms. Common presenting symptoms and associated neuro-orbital diseases
      also are summarized.

PMID- 27886891
TI  - The Yield of Diagnostic Imaging in Patients with Isolated Horner Syndrome.
AB  - We sought to determine, with a retrospective chart review, the imaging yield for
      patients with clinically isolated Horner syndrome. MRI/MRA of the head and neck
      extending from the supraorbital ridge to T4 with fat suppression and with
      postcontrast images was obtained. Of 88 patients with isolated Horner syndrome
      who were imaged, 20% had a causative etiology on imaging. The most common cause
      of an isolated Horner syndrome was a carotid artery dissection. There was 1
      patient with a primary malignancy found to be the causative lesion in this group,
      and 1 patient with spread of their known metastatic disease.

PMID- 27886892
TI  - Optical Coherence Tomography in Neuro-ophthalmology.
AB  - The afferent visual pathway is a functionally eloquent region of the central
      nervous system (CNS). Key clinical features of inflammatory, ischemic, and
      compressive CNS lesions can be appreciated through detailed ophthalmic
      examination. Optical coherence tomography (OCT) provides a noninvasive means of
      capturing manifestations of axonal and neuronal loss in the CNS. OCT represents a
      surrogate marker of structural integrity in the CNS, through which mechanisms of
      neurodegeneration and repair may be better understood. In this article, the role
      of OCT in facilitating the diagnosis and management of several CNS disorders is
      discussed.

PMID- 27886893
TI  - Erectile Dysfunction Agents and Nonarteritic Anterior Ischemic Optic Neuropathy.
AB  - Phosphodiesterase-5 inhibitors (PDE5I) are used for treatment of erectile
      dysfunction and pulmonary arterial hypertension and have been implicated as a
      causative factor for development of nonarteritic anterior ischemic optic
      neuropathy (NAION). Controversy remains regarding a cause and effect between
      PDE5I use and NAION because the mechanism by which NAION occurs is still not well
      understood. Because neuro-ophthalmologists have accepted that there is a
      potential relationship between ingestion of the PDE5I class of medications and
      NAION, the neuro-ophthalmologist should inquire about PDE5I use when evaluating a
      patient with a new diagnosis of NAION, and counsel patients regarding the
      implication of continued use of PDE5I.

PMID- 27886894
TI  - Homonymous Hemianopia and Vision Restoration Therapy.
AB  - Homonymous hemianopia from stroke causes visual disability. Although some
      patients experience spontaneous improvement, others have limited to no change and
      may be left with a severe disability. Current rehabilitation strategies are
      compensatory and cannot restore function. Animal studies suggest that central
      nervous system plasticity could allow for redirection of lost visual function
      into undamaged areas of cortex. A commercial therapy system was developed, from
      which claims of visual field expansion were disputed by independent researchers.
      The treatment remains controversial with seemingly contradictory data being
      generated. Continued research is underway to demonstrate the (non-)efficacy of
      this treatment method.

PMID- 27886895
TI  - Update on Idiopathic Intracranial Hypertension.
AB  - Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial
      pressure of unknown cause occurring predominantly in young women of childbearing
      age. The typical patient symptom profile is the presence of daily headache, pulse
      synchronous tinnitus, transient visual obscurations, and papilledema with its
      associated visual loss. Although surgical procedures are performed for those who
      fail medical therapy, their relative efficacy remains unclear. The main morbidity
      of IIH is from visual loss. This visual loss is present in most patients and can
      usually be reversed if recognized early in the patients' course and treated.

PMID- 27886896
TI  - Venous Sinus Stenting for Idiopathic Intracranial Hypertension: Where Are We Now?
AB  - Idiopathic intracranial hypertension causes headache, papilledema and visual
      field loss, typically in obese women of childbearing age. Its anatomical
      underpinnings remain unclear, but a stenosis at the junction of the transverse
      and sigmoid sinuses has been recognized in the majority of patients through
      venography. The stenosis may result from intrinsic dural sinus anatomy or
      extrinsic compression by increased intracranial pressure, but in either case, its
      stenting has been shown to lead to an improvement in symptoms of intracranial
      hypertension and papilledema in multiple retrospective, non-controlled studies.
      Prospective, controlled trials are needed to confirm its efficacy and safety.

PMID- 27886897
TI  - Update on the Management of Central Retinal Artery Occlusion.
AB  - Central retinal artery occlusion (CRAO) is caused by partial or complete
      occlusion of the central retinal artery, most commonly by an embolus from the
      ipsilateral carotid artery, aortic arch, or heart, and is the ocular equivalent
      of an acute cerebral ischemic event. The risk factors for a CRAO and acute
      cerebral ischemia are very similar, if not identical. Because no current
      therapeutic intervention has been shown to improve visual outcomes compared with
      the natural history of CRAO, management of CRAO should be focused on secondary
      prevention of vascular events, such as cerebral ischemia, myocardial infarction,
      and cardiovascular death.

PMID- 27886898
TI  - Neuro-Ophthalmology for Neurologists.

PMID- 27886900
TI  - Differential Diagnosis of Atopic Dermatitis.
AB  - Atopic dermatitis (AD) is a common inflammatory condition of the skin that is
      usually seen in childhood, but can onset or persist into adulthood. The
      characteristic distribution and morphology based on age, chronic relapsing
      course, and pruritus comprise the clinical criteria used in the diagnosis of AD.
      However, the numerous morphologies ranging from acute, weeping erythematous
      papules to chronic lichenified plaques, can be simulated by multiple other
      conditions, including inflammatory, infectious, neoplastic, and photo-dermatoses.
      Recognition of the distinguishing features and clinical mimickers of atopic
      dermatitis is vital for an accurate and timely diagnosis, and initiation of
      proper treatment regimens.

PMID- 27886901
TI  - Itch in Atopic Dermatitis.
AB  - Chronic itch in inflammatory skin diseases, such as atopic dermatitis, markedly
      diminishes the quality of life of affected individuals. Comprehensive progress
      has been made in understanding itch signaling and associated mediators in the
      skin, dorsal root ganglia, spinal cord, and central nervous system, which may
      amplify or suppress atopic itch. Conventional therapies for atopic dermatitis are
      capable of reducing atopic itch; however, most patients are not satisfied with
      the antipruritic capacity of conventional treatments. Exploring itch pathways and
      mechanisms may lead to novel therapeutic approaches for atopic itch.

PMID- 27886899
TI  - Atopic Dermatitis and Allergic Urticaria: Cutaneous Manifestations of
      Immunodeficiency.
AB  - Atopic dermatitis and allergic urticaria are common conditions of the skin that
      can also be the presenting symptoms of uncommon diseases. Defects leading to
      immunodeficiency may be associated with atopic dermatitis or allergic urticaria.
      Unusually severe or otherwise atypical presentations of atopic dermatitis or
      allergic urticaria may lead to clinical suspicion of an underlying
      immunodeficiency.

PMID- 27886902
TI  - Wet Wrap Therapy in Moderate to Severe Atopic Dermatitis.
AB  - National and international guidelines address stepwise atopic dermatitis (AD)
      management. Wet wrap therapy (WWT) is important as an acute therapeutic
      intervention for treatment of moderate to severe AD. Using clothing instead of
      bandages makes this intervention simpler, less time intensive, and less
      expensive. Education of patients and caregivers is critical to success;
      methodology must be standardized. Future studies must carefully describe all
      procedure components. Incorporation of validated outcomes tools would help with
      interpretation. WWT should be considered as a potential treatment option ahead of
      systemic immunosuppressive therapies for patients failing conventional therapy.

PMID- 27886903
TI  - Allergic Contact Dermatitis.
AB  - Allergic contact dermatitis (ACD) is a common skin disease caused by a T cell
      mediated immune reaction to usually innocuous allergens. ACD can have grave
      medical and socioeconomic consequences. ACD and irritant contact dermatitis often
      occur together. A detailed history and clinical examination are crucial and guide
      patch testing, which is the gold standard to diagnose ACD. T-cell clones
      persisting in the skin may explain the tendency of ACD to relapse even after
      years of allergen avoidance. Traditional treatments for ACD are topical steroids,
      calcineurin inhibitors, phototherapy, retinoids (including the recent
      alitretinoin), and immunosuppressants. Targeted therapies are lacking.

PMID- 27886904
TI  - Mastocytosis and Anaphylaxis.
AB  - This article updates current knowledge on epidemiology, risk factors, triggers,
      and management of anaphylaxis in patients with mastocytosis. Hyperactive mast
      cells and higher number of effector mast cells are speculated to facilitate
      anaphylaxis in this condition. In children, increased risk is limited to those
      with extensive skin involvement and high tryptase. In adults, manifestations of
      anaphylaxis are severe with high frequency of cardiovascular symptoms.
      Hymenoptera stings are the most common triggers for these reactions; however,
      idiopathic anaphylaxis and reactions to food or drugs occur. Patients with
      mastocytosis should be informed about risk of anaphylaxis and prescribing
      emergency self-medication and installing emergency preparedness before general
      anesthesia is considered.

PMID- 27886905
TI  - Cutaneous Manifestation of Drug Allergy and Hypersensitivity.
AB  - Drug hypersensitivity reactions may manifest with either organ-specific or
      systemic symptoms, but cutaneous eruptions are the most common manifestations.
      Different medications may cause identical skin symptoms, whereas hypersensitivity
      to a single drug may manifest with various patterns of symptoms depending on the
      pathomechanism of hypersensitivity. Drug reactions should be also taken into
      account in the differential diagnosis of numerous skin rashes. Analysis of
      morphology of drug-induced lesions, about potential immunologic or
      nonimmunological mechanisms, is important for the final diagnosis. Thus, here the
      authors present a morphologic approach to the diagnosis of cutaneous drug-induced
      eruptions.

PMID- 27886906
TI  - The Angiotensin-Converting-Enzyme-Induced Angioedema.
AB  - The bradykinin B2 receptor antagonist icatibant is effective in angiotensin
      converting enzyme inhibitor-induced angioedema. The drug is not approved
      officially for this indication and has to be administered in an emergency
      situation off-label. Corticosteroids or antihistamines do not seem to work in
      this condition. The effectiveness of C1-esterase-inhibitor in angiotensin
      converting enzyme-induced angioedema must be verified in a double-blind study.

PMID- 27886908
TI  - Cutaneous Manifestation of Food Allergy.
AB  - Hypersensitivity reactions to foods can have diverse and highly variable
      manifestations. Cutaneous reactions, such as acute urticaria and angioedema, are
      among the most common manifestations of food allergy. However, cutaneous
      manifestations of food allergy encompass more than just IgE-mediated processes
      and include atopic dermatitis, contact dermatitis, and even dermatitis
      herpetiformis. These cutaneous manifestations provide an opportunity to better
      understand the diversity of adverse immunologic responses to food and the
      interconnected pathways that produce them.

PMID- 27886907
TI  - Differential Diagnosis of Chronic Urticaria and Angioedema Based on Molecular
      Biology, Pharmacology, and Proteomics.
AB  - Differential diagnosis of urticaria and angioedema has been based on the
      phenotype as either acute or chronic depending on the duration of more than 6 to
      8 weeks, respectively. Additional subdivisions include poorly defined terms such
      as idiopathic, spontaneous, or autoimmune. In this article, the author suggests
      that an increased understanding of the acquired and innate immune system and data
      from novel proteomic technology have blurred the lines between these categories
      of diagnosis. Specific molecular pathways and response to specific medications
      should be incorporated in classification and diagnosis schemes.

PMID- 27886909
TI  - Clinical Measures of Chronic Urticaria.
AB  - The use of standardized, valid, and reliable clinical measures is an important
      element in modern patient management, particularly in diseases that are not
      objectively assessable and are associated with a high disease burden. Chronic
      urticaria is such a disorder for which several new and well-developed clinical
      measures became available. These measures comprise tools to assess disease
      activity, disease control, and health-related quality-of-life impairment. This
      review provides an overview of the currently available clinical measures for
      chronic urticaria. In addition, it provides information on their strengths and
      limitations and how to best use them and evaluate their results.

PMID- 27886910
TI  - Current and Future Biomarkers in Atopic Dermatitis.
AB  - Atopic dermatitis (AD) is a heterogeneous disease and many attempts have been
      made to define subsets of patients based on clinical characteristics. However,
      the current characterization of patients with AD might not adequately reflect the
      pathophysiologic diversity within patients with AD. This article reviews current
      biomarkers for AD and future perspectives. In the future, patients with AD will
      be stratified based on biomarker expression levels in body fluids and tissue,
      genetic variants, or combined biomarker expression patterns. With new targeted
      therapies for AD currently investigated in clinical trials this will lead to
      better identification of patients that can benefit from these highly specific,
      but expensive new treatments.

PMID- 27886911
TI  - The Role of Fungi in Atopic Dermatitis.
AB  - There is little doubt that Malassezia spp plays a role in atopic dermatitis
      because it may interact with the local skin immune responses and barrier
      function, and sensitization against this skin-colonizing yeast can correlate with
      disease activity. Also, antifungal therapy shows beneficial effects in some
      patients. However, the pathogenetic mechanism and mutual interaction between
      Malassezia spp and atopic dermatitis still remain partly unclear and need further
      investigation.

PMID- 27886912
TI  - Infectious Complications in Atopic Dermatitis.
AB  - Atopic dermatitis is characterized by the interplay of skin barrier defects with
      the immune system and skin microbiome that causes patients to be at risk for
      infectious complications. This article reviews the pathogenesis of atopic
      dermatitis and the mechanisms through which patients are at risk for infection
      from bacterial, viral, and fungal pathogens. Although these complications may be
      managed acutely, prevention of secondary infections depends on a multipronged
      approach in the maintenance of skin integrity, control of flares, and microbial
      pathogens.

PMID- 27886913
TI  - Biologics in Chronic Urticaria.
AB  - Chronic urticaria (CU) is defined as wheals, angioedema, or both, that last more
      than 6 weeks. Second-generation antihistamines are considered the first-line
      therapy for CU. Unfortunately, many patients will fail antihistamines and require
      alternative therapy, including immune response modifiers or biologics. Multiple
      biological agents have been evaluated for use in antihistamine-refractory CU,
      including omalizumab, rituximab, and intravenous immunoglobulin; omalizumab is
      the most efficacious. Because of the success of omalizumab, multiple new
      biologics that are directed at the IgE pathway are under investigation. This
      review summarizes the relevant data regarding the efficacy of biologics in
      antihistamine-refractory CU.

PMID- 27886915
TI  - Allergic Skin Diseases.

PMID- 27886914
TI  - Allergic Skin Disease and the Practicing Allergist: Growing Unmet Need, New
      Science, and New Treatments.

PMID- 27886916
TI  - Understanding Heart Failure.
AB  - Heart failure (HF) is a growing global health concern that affects more than 20
      million people worldwide. With an ever-growing segment of the population over the
      age of 65, the prevalence of HF and its associated costs are expected to increase
      exponentially over the next decade. Advances in the understanding of the
      pathophysiology and treatment of HF have resulted in the ability to enhance both
      the quantity and the quality of life of patients with HF. This article reviews
      the current understanding of the pathophysiology, cause, classification, and
      treatment of HF and describes areas of uncertainty that demand future study.

PMID- 27886917
TI  - Coronary Sinus Lead Extraction.
AB  - Expanded indications for cardiac resynchronization therapy and the increasing
      incidence of cardiac implantable electronic device infection have led to an
      increased need for coronary sinus (CS) lead extraction. The CS presents unique
      anatomical obstacles to successful lead extraction. Training and facility
      requirements for CS lead extraction should mirror those for other leads. Here we
      review the indications, technique, and results of CS lead extraction. Published
      success rates and complications are similar to those reported for other leads,
      although multiple techniques may be required. Re-implantation options may be
      limited, which should be incorporated into pre-procedural decision making.

PMID- 27886918
TI  - Cardiac Resynchronization Therapy: An Overview on Guidelines.
AB  - Cardiac resynchronization therapy (CRT) is included in international consensus
      guidelines as a treatment with proven efficacy in well-selected patients on top
      of optimal medical therapy. Although all the guidelines strongly recommend CRT
      for LBBB with QRS duration greater than 150 milliseconds, lower strength of
      recommendation is reported for QRS duration of 120 to 150 milliseconds,
      especially if not associated with LBBB. CRT is not recommended for a QRS of less
      than 120 milliseconds. No indication emerges for guiding the implant based on
      echocardiographic evaluation of dyssynchrony. Many data indicate that CRT is
      underused and there is heterogeneity in its implementation.

PMID- 27886919
TI  - Why the Authors Use Cardiac Resynchronization Therapy with Defibrillators.
AB  - Cardiac resynchronization therapy (CRT) improves left ventricular function,
      especially in patients with left bundle branch block or those receiving chronic
      right ventricular pacing. CRT is typically accomplished by placing a right
      ventricular endocardial pacing lead and a left ventricular pacing lead via the
      coronary sinus to a coronary vein overlying the lateral or posterolateral left
      ventricle. CRT can be combined with an implantable defibrillator or with a
      pacemaker. Limited data are available to compare these two versions of CRT head
      to head. This review summarizes the relevant trials and meta-analyses regarding
      these two forms of CRT.

PMID- 27886920
TI  - Why We Have to Use Cardiac Resynchronization Therapy-Pacemaker More.
AB  - Both cardiac resynchronization therapy with a pacemaker (CRT-P) and with a
      biventricular implantable cardioverter-defibrillator (CRT-D) are electrical
      treatment modalities validated for the management of chronic heart failure. There
      is no strong scientific evidence that a CRT-D must be offered to all candidates.
      Common sense should limit the prescription of these costly and complicated
      devices. The choice of CRT-P is currently acceptable. A direction to explore
      could be to downgrade from CRT-D to CRT-P at the time of battery depletion in
      patients with large reverse remodeling and no ventricular tachycardia and
      ventricular fibrillation detected.

PMID- 27886922
TI  - Atrial Fibrillation During Cardiac Resynchronization Therapy.
AB  - The landmark trials on cardiac resynchronization therapy (CRT) have focused on
      patients with sinus rhythm at inclusion. Little data are available on the
      efficacy of CRT in patients with atrial fibrillation (AF), while AF has a high
      prevalence (20-40%) among patients receiving CRT. This review focuses on the
      detrimental effect of AF on CRT response and discusses management of patients
      with AF during CRT. Uncertainty remains as to which thresholds of AF burden can
      lead to a reduced response to CRT and every effort should be made in trying to
      assess and guarantee successful biventricular pacing in patients with AF.

PMID- 27886921
TI  - Cardiac Resynchronization Therapy in Women.
AB  - The benefits of cardiac resynchronization therapy (CRT) on the outcomes of
      patients with heart failure are unquestionable. Women are under-represented in
      all CRT studies. Most of the available data show that CRT produces a greater
      clinical benefit in women than men. In several studies, women have left bundle
      branch block more frequently than men. Women have a remarkably high (90%) CRT
      response over a wide range of QRS lengths (130-175 milliseconds). Use of a QRS
      duration of 150 milliseconds as the threshold for CRT prescription may deny a
      life-saving therapy to many women likely to benefit from CRT.

PMID- 27886923
TI  - Atrioventricular Node Ablation.
AB  - Cardiac resynchronization therapy (CRT) is a device-based, nonpharmacologic
      approach that has shown to improve the outcome in patients with heart failure in
      terms of mortality and morbidity reduction. Large randomized trials have
      virtually enrolled patients in New York Heart Association class III-IV, with
      reduced left ventricular ejection fraction, with evidence of electrical
      dyssynchrony, and receiving optimal medical therapy and who were in sinus rhythm.
      Guidelines remain imprecise as to defining differentiated approaches according to
      the forms of atrial fibrillation other than permanent. These recommendations
      remain unsupported by evidence derived from randomized controlled trials, which
      are much needed.

PMID- 27886924
TI  - How to Improve Cardiac Resynchronization Therapy Benefit in Atrial Fibrillation
      Patients: Pulmonary Vein Isolation (and Beyond).
AB  - Although cardiac resynchronization therapy (CRT) is an important treatment of
      symptomatic heart failure patients in sinus rhythm with low left ventricular
      ejection fraction and ventricular dyssynchrony, its role is not well defined in
      patients with atrial fibrillation (AF). CRT is not as effective in patients with
      AF because of inadequate biventricular capture and loss of atrioventricular
      synchrony. Both can be addressed with catheter ablation of AF. It is still
      unclear if these therapies offer additive benefits in patients with ventricular
      dyssynchrony. This article discusses the role and techniques of catheter ablation
      of AF in patients with heart failure, and its application in CRT recipients.

PMID- 27886925
TI  - The Role of Atrioventricular and Interventricular Optimization for Cardiac
      Resynchronization Therapy.
AB  - Many patients with left ventricular systolic dysfunction may benefit from cardiac
      resynchronization therapy; however, approximately 30% of patients do not
      experience significant clinical improvement with this treatment. AV and VV delay
      optimization techniques have included echocardiography, device-based algorithms,
      and several other novel noninvasive techniques. Using these techniques to
      optimize device settings has been shown to improve hemodynamic function acutely;
      however, the long-term clinical benefit is limited. In most cases, an empiric AV
      delay with simultaneous biventricular or left ventricular pacing is adequate. The
      value of optimization of these intervals in "nonresponders" still requires
      further investigation.

PMID- 27886926
TI  - Containing the Cost of Heart Failure Management: A Focus on Reducing
      Readmissions.
AB  - Heart failure (HF) consumes a large proportion of the total national health care
      budget. Incidence and prevalence of HF are increasing and may give rise to an
      unsustainable increase in health care spending. Hospitalizations account for the
      vast majority of HF-related expenses, and 20% to 25% of patients discharged with
      a diagnosis of HF are readmitted within 60 days. Thus, efforts to reduce HF
      readmissions are a reasonable target for reducing overall expenses. It is to be
      seen if targeting readmission rates will lead to significant cost savings, and
      more importantly, to improved patient outcomes.

PMID- 27886927
TI  - What We Can Learn from "Super-responders".
AB  - This review discusses the state of the art of knowledge to help decision making
      in patients who are candidates for cardiac resynchronization therapy (CRT) and to
      analyze the long-term total and cardiac mortality, sudden death, and CRT with a
      defibrillator intervention rate, as well as the evolution of echocardiographic
      parameters in patients with a left ventricular (LV) ejection fraction of greater
      than 50% after CRT implantation. Owing to normalization of LV function in super
      responders, the need for a persistent defibrillator backup is also considered.

PMID- 27886928
TI  - Cardiac Resynchronization Therapy: How to Decrease Nonresponders.
AB  - Nonresponse to cardiac resynchronization therapy (CRT) is still a major issue in
      therapy expansion. The description of fast, simple, cost-effective methods to
      optimize CRT could help in adapting pacing intervals to individual patients. A
      better understanding of the importance of appropriate patient selection, left
      ventricular lead placement, and device programming, together with a
      multidisciplinary approach and an optimal follow-up of the patients, may reduce
      the percentage of nonresponders.

PMID- 27886930
TI  - Cellular and Molecular Aspects of Dyssynchrony and Resynchronization.
AB  - Dyssynchronous contraction of the ventricle significantly worsens morbidity and
      mortality in patients with heart failure (HF). Approximately one-third of
      patients with HF have cardiac dyssynchrony and are candidates for cardiac
      resynchronization therapy (CRT). The initial understanding of dyssynchrony and
      CRT was in terms of global mechanics and hemodynamics, but lack of clinical
      benefit in a sizable subgroup of recipients who appear otherwise appropriate has
      challenged this paradigm. This article reviews current understanding of these
      cellular and subcellular mechanisms, arguing that these aspects are key to
      improving CRT use, as well as translating its benefits to a wider HF population.

PMID- 27886929
TI  - Cardiac Resynchronization Therapy Follow-up: Role of Remote Monitoring.
AB  - Cardiac resynchronization therapy (CRT) is increasingly used in heart failure
      treatment and management of these patients imposes significant challenges. Remote
      monitoring is becoming essential for CRT follow-up and allows close surveillance
      of device function and patient condition. It is helpful to reduce clinic visits,
      increase device longevity and provide early detection of device failure. Clinical
      effects include prevention of appropriate and inappropriate shocks and early
      detection of arrhythmias, such as atrial fibrillation. For modification of heart
      failure the addition of monitoring to CRT by means of device-based
      multiparameters may help to modify disease progression and improve survival.

PMID- 27886931
TI  - Exploring the Electrophysiologic and Hemodynamic Effects of Cardiac
      Resynchronization Therapy: From Bench to Bedside and Vice Versa.
AB  - Cardiac resynchronization therapy (CRT) is an important therapy for heart failure
      patients with prolonged QRS duration. In patients with left bundle branch block
      the altered left ventricular electrical activation results in dyssynchronous,
      inefficient contraction of the left ventricle. CRT aims to reverse these changes
      and to improve cardiac function. This article explores the electrophysiologic and
      hemodynamic changes that occur during CRT in patient and animal studies. It also
      addresses how novel techniques, such as multipoint and endocardial pacing, can
      further improve the electromechanical response.

PMID- 27886932
TI  - Newer Echocardiographic Techniques in Cardiac Resynchronization Therapy.
AB  - Echocardiographic imaging plays a major role in patient selection for cardiac
      resynchronization therapy (CRT). One-third of patients do not respond; there is
      interest in advanced echocardiographic imaging to improve response. Current
      guidelines favor CRT for patients with electrocardiographic (ECG) QRS width of
      150 milliseconds or greater and left bundle branch block. ECG criteria are
      imperfect; there is interest in advanced echocardiographic imaging to improve
      patient selection. This discussion focuses on newer echocardiographic methods to
      improve patient selection, improve delivery, and identify patients at risk for
      poor outcomes and serious ventricular arrhythmias.

PMID- 27886933
TI  - The Role of Cardiovascular Magnetic Resonance in Cardiac Resynchronization
      Therapy.
AB  - Randomized, controlled trials have shown that cardiac resynchronization therapy
      (CRT) is beneficial in patients with heart failure, impaired left ventricular
      (LV) systolic function, and a wide QRS complex. Other studies have shown that
      targeting the LV pacing site can also improve patient outcomes. Cardiovascular
      magnetic resonance (CMR) is a radiation-free imaging modality that provides
      unparalleled spatial resolution. In addition, emerging data suggest that targeted
      LV lead deployment over viable myocardium improves the outcome of patients
      undergoing CRT. This review explores the role of CMR in the preoperative workup
      of patients undergoing CRT.

PMID- 27886934
TI  - Coronary Sinus Lead Positioning.
AB  - Although cardiac resynchronization therapy improves morbidity and mortality in
      patients with cardiomyopathy, heart failure, and electrical dyssynchrony, the
      rate of nonresponders using standard indications and implant techniques is still
      high. Optimal coronary sinus lead positioning is important to increase the chance
      of successful resynchronization. Patient factors such as cause of heart failure,
      type of dyssynchrony, scar burden, coronary sinus anatomy, and phrenic nerve
      capture may affect the efficacy of the therapy. Several modalities are under
      investigation. Alternative left ventricular lead implantation strategies are
      occasionally required when the transvenous route is not feasible or would result
      in a suboptimal lead position.

PMID- 27886935
TI  - Robotic-Assisted Left Ventricular Lead Placement.
AB  - Robot-assisted left ventricular lead implantation for cardiac resynchronization
      therapy is a feasible and safe technique with superior visualization, dexterity,
      and precision to target the optimal pacing site. The technique has been
      associated with clinical response and beneficial reverse remodeling comparable
      with the conventional approach via the coronary sinus. The lack of clinical
      superiority and a residual high nonresponder rate suggest that the appropriate
      clinical role for the technique remains as rescue therapy.

PMID- 27886936
TI  - Extending evidence to practice: Implementation of Models of Care for
      musculoskeletal health conditions across settings.

PMID- 27886937
TI  - Models of Care for musculoskeletal health: Moving towards meaningful
      implementation and evaluation across conditions and care settings.
AB  - Models of Care (MoCs) are increasingly recognised as a system-level enabler to
      translate evidence for 'what works' into policy and, ultimately, clinical
      practice. MoCs provide a platform for a reform agenda in health systems by
      describing not only what care to deliver but also how to deliver it. Given the
      enormous burden of disease associated with musculoskeletal (MSK) conditions,
      system-level (macro) reform is needed to drive downstream improvements in MSK
      healthcare - at the health service (meso) level and at the clinical interface
      (micro) level. A key challenge in achieving improvements in MSK healthcare is
      sustainable implementation of reform initiatives, whether they be macro, meso or
      micro level in scope. In this chapter, we introduce the special issue of the
      Journal dedicated to implementation of MSK MoCs. We provide a contextual
      background on MoCs, a synthesis of implementation approaches across care settings
      covered across the chapters in this themed issued, and perspectives on the
      evaluation of MoCs.

PMID- 27886938
TI  - Implementation of musculoskeletal Models of Care in primary care settings:
      Theory, practice, evaluation and outcomes for musculoskeletal health in high
      income economies.
AB  - Musculoskeletal conditions represent one of the largest causes of years lived
      with disability in high-income economies. These conditions are predominantly
      managed in primary care settings, and yet, there is a paucity of evidence on
      which approaches work well in increasing the uptake of best practice and in
      closing the evidence-to-practice gap. Increasingly, musculoskeletal models of
      service delivery (as components of models of care) such as integrated care,
      stratified care and therapist-led care have been tested in primary health care
      pathways for joint pain in older adults, for low back pain and for arthritis. In
      this chapter, we discuss why implementation of these models is important for
      primary care and how models are implemented using three case examples: we review
      implementation theory, principles and outcomes; we consider the role of health
      economic evaluation; and we propose key evidence gaps in this field. We propose
      the following research priorities for this area: investigating the
      generalisability of models of care across, for example, urban and rural settings,
      and for different musculoskeletal conditions; increasing support for self
      management; understanding the importance of context in choosing a model of care;
      detailing how implementation has been undertaken; and evaluation of
      implementation and its impact.

PMID- 27886939
TI  - Development and implementation of Models of Care for musculoskeletal conditions
      in middle-income and low-income Asian countries.
AB  - This chapter discusses the challenges faced in the development and implementation
      of musculoskeletal (MSK) Models of Care (MoCs) in middle-income and low-income
      countries in Asia and outlines the components of an effective MoC for MSK
      conditions. Case studies of four such countries (The Philippines, Malaysia,
      Bangladesh and Myanmar) are presented, and their unique implementation issues are
      discussed. The success experienced in one high-income country (Singapore) is also
      described as a comparison. The Community Oriented Program for Control of
      Rheumatic Diseases (COPCORD) project and the role of Asia Pacific League of
      Associations for Rheumatology (APLAR), a professional body supporting MoC
      initiatives in this region, are also discussed. The experience and lessons
      learned from these case studies can provide useful information to guide the
      implementation of future MSK MoC initiatives in other middle-income and low
      income countries.

PMID- 27886940
TI  - Harnessing and supporting consumer involvement in the development and
      implementation of Models of Care for musculoskeletal health.
AB  - Consumer involvement in the design and delivery of their healthcare is an
      integral strategy to ensure that health services and systems meet consumers'
      needs. This is also true for the design and delivery of Models of Care. This
      chapter presents the identified healthcare needs of people with musculoskeletal
      conditions and focuses on the current systematic review evidence for consumer
      involvement interventions in musculoskeletal Models of Care across the micro,
      meso and macro levels of healthcare. This chapter also presents three case
      studies of consumer involvement in different aspects of healthcare, offers a
      series of practice points to help translate the systematic review evidence into
      practice, and also provides direction to available resources, which support the
      implementation of consumer involvement within Models of Care.

PMID- 27886941
TI  - Management of musculoskeletal pain in a compensable environment: Implementation
      of helpful and unhelpful Models of Care in supporting recovery and return to
      work.
AB  - Models of Care (MoCs) for injured workers in the compensation environment
      recommend adoption of biopsychosocial management approaches. Still, widespread
      dominance of biomedical constructs at the system, organisational and individual
      levels of the compensation system prevails, contributing to suboptimal management
      practices and outcomes for injured workers. Efforts to implement contemporary
      MoCs in the compensation environment show some promise in improving outcomes.
      Areas of promise at the organisational level, particularly in the workplace, and
      at the system level are discussed. Implementation of a contemporary understanding
      of pain biology as part of the biopsychosocial approach in the management of the
      person with pain and associated disability has been effective in the non
      compensable environment. The implications of this for the compensable environment
      are explored. Resultant helpful and unhelpful perspectives and behaviours are
      presented as a blueprint for areas of potential change in development and
      implementation of MoCs in a compensable environment.

PMID- 27886942
TI  - Models of Care for addressing chronic musculoskeletal pain and health in children
      and adolescents.
AB  - Chronic musculoskeletal pain among children and adolescents is common and can
      negatively affect quality of life. It also represents a high burden on the health
      system. Effective models of care for addressing the prevention and management of
      pediatric musculoskeletal pain are imperative. This chapter will address the
      following key questions: (1) Why are pediatric-specific models of pain care
      needed? (2) What is the burden of chronic musculoskeletal pain among children and
      adolescents? (3) What are the best practice approaches for early identification
      and prevention of chronic musculoskeletal pain in children and adolescents? (4)
      What are the recommended strategies for clinical management of chronic pain,
      including pharmacological, physical, psychological and complementary, and
      alternative approaches? (5) What are the most effective strategies for
      implementing models of pain care across different care settings? (6) What are the
      research priorities to improve models of care for children and adolescents with
      chronic musculoskeletal pain?

PMID- 27886943
TI  - Use of eHealth technologies to enable the implementation of musculoskeletal
      Models of Care: Evidence and practice.
AB  - Musculoskeletal (MSK) conditions are the second leading cause of morbidity
      related burden of disease globally. EHealth is a potentially critical factor that
      enables the implementation of accessible, sustainable and more integrated MSK
      models of care (MoCs). MoCs serve as a vehicle to drive evidence into policy and
      practice through changes at a health system, clinician and patient level. The use
      of eHealth to implement MoCs is intuitive, given the capacity to scale
      technologies to deliver system and economic efficiencies, to contribute to
      sustainability, to adapt to low-resource settings and to mitigate access and care
      disparities. We follow a practice-oriented approach to describing the 'what' and
      'how' to harness eHealth in the implementation of MSK MoCs. We focus on the
      practical application of eHealth technologies across care settings to those MSK
      conditions contributing most substantially to the burden of disease, including
      osteoarthritis and inflammatory arthritis, skeletal fragility-associated
      conditions and persistent MSK pain.

PMID- 27886944
TI  - Osteoarthritis: Models for appropriate care across the disease continuum.
AB  - Osteoarthritis (OA) is a leading cause of pain and disability worldwide. Despite
      the existence of evidence-based treatments and guidelines, substantial gaps
      remain in the quality of OA management. There is underutilization of behavioral
      and rehabilitative strategies to prevent and treat OA as well as a lack of
      processes to tailor treatment selection according to patient characteristics and
      preferences. There are emerging efforts in multiple countries to implement models
      of OA care, particularly focused on improving nonsurgical management. Although
      these programs vary in content and setting, key lessons learned include the
      importance of support from all stakeholders, consistent program delivery and
      tools, a coherent team to run the program, and a defined plan for outcome
      assessment. Efforts are still needed to develop, deliver, and evaluate models of
      care across the spectrum of OA, from prevention through end-stage disease, in
      order to improve care for this highly prevalent global condition.

PMID- 27886945
TI  - Implementation of Models of Care for secondary osteoporotic fracture prevention
      and orthogeriatric Models of Care for osteoporotic hip fracture.
AB  - As the world's population ages, the prevalence of osteoporosis and its resultant
      fragility fractures is set to increase dramatically. This chapter focuses on
      current frameworks and major initiatives related to the implementation of
      fracture liaison services (FLS) and orthogeriatrics services (OGS), Models of
      Care designed to reliably implement secondary fracture prevention measures for
      individuals presenting to health services with fragility fractures. The current
      evidence base regarding the impact and effectiveness of FLS and OGS is also
      considered.

PMID- 27886946
TI  - Building multidisciplinary health workforce capacity to support the
      implementation of integrated, people-centred Models of Care for musculoskeletal
      health.
AB  - To address the burden of musculoskeletal (MSK) conditions, a competent health
      workforce is required to support the implementation of MSK models of care.
      Funding is required to create employment positions with resources for service
      delivery and training a fit-for-purpose workforce. Training should be aligned to
      define "entrustable professional activities", and include collaborative skills
      appropriate to integrated and people-centred care and supported by shared
      education resources. Greater emphasis on educating MSK healthcare workers as
      effective trainers of peers, students and patients is required. For quality,
      efficiency and sustainability of service delivery, education and research
      capabilities must be integrated across disciplines and within the workforce, with
      funding models developed based on measured performance indicators from all three
      domains. Greater awareness of the societal and economic burden of MSK conditions
      is required to ensure that solutions are prioritised and integrated within
      healthcare policies from local to regional to international levels. These
      healthcare policies require consumer engagement and alignment to social,
      economic, educational and infrastructure policies to optimise effectiveness and
      efficiency of implementation.

PMID- 27886948
TI  - Variation in Hospital Intrapartum Practices and Association With Cesarean Rate.
AB  - OBJECTIVE: To examine hospital variation in intrapartum care and its relationship
      with cesarean rates. DESIGN: Cross-sectional survey. SETTING: Connecticut and
      Massachusetts hospitals providing obstetric services. PARTICIPANTS: Nurse
      managers or other clinical staff knowledgeable about intrapartum care. METHODS:
      We assessed labor and delivery unit capacity and staffing, fetal monitoring,
      labor management, intrapartum interventions, newborn care, quality assurance, and
      performance review practices. Association of hospital characteristics and
      intrapartum practices with cesarean rate was evaluated using Wilcoxon exact rank
      sum test and Kendall's tau-b correlation coefficient. RESULTS: Among 60 eligible
      hospitals, respondents from 39 hospitals (65%) completed the survey. Cesarean
      rates varied from 21% to 42% (median = 30%). Regular review of cesarean rates and
      indications (85%), regular provision of feedback on cesarean rates and
      indications to physicians (80%), and regular review of vaginal birth after
      cesarean rates (94%) were commonly performed at responding hospitals. These
      practices, however, were not associated with hospital cesarean rate. Hospitals
      that offered cesarean at the request of the woman (p < .01) and had more liberal
      indications for labor induction (p < .01) and cesarean birth (p < .01) had
      significantly greater cesarean rates than institutions without these practices.
      Routinely placing an intravenous line (p < .01) and drawing blood for complete
      blood count/type and antibody screen (p < .01) in low-risk women were associated
      with greater cesarean rates; having a certified nurse-midwife in house at all
      times (p = .01) and permitting women to eat during labor (p = .02) were
      associated with lower cesarean rates. CONCLUSION: Intrapartum practices of
      hospitals varied markedly. These different patterns of care may suggest differing
      levels of intrapartum intervention.

PMID- 27886947
TI  - Utilization of electroencephalogram post cardiac arrest in the United States: A
      nationwide retrospective cohort analysis.
AB  - OBJECTIVE: The use of electroencephalogram (EEG) has been demonstrated to have
      diagnostic and prognostic value in cardiac arrest patients. The use of this
      modality across the United States in this population is unknown. METHODS: The
      Nationwide Inpatient Sample (NIS) is a federal database capturing 20% of all US
      hospital admissions. A cohort of patients who suffered both in and out of
      hospital cardiac arrests from the 2006 to 2012 NIS datasets was created. RESULTS:
      The records of 55,208,382 hospitalizations were analyzed, of which 207,703
      patients suffered a cardiac arrest. There were 2952 (1.42%) patients who also had
      an EEG. Patients who had an EEG compared to those who did not were: younger (62.2
      years SD 16.6 vs 66.9 years SD 16.2, p<0.01), were less likely to have insurance
      coverage (89.9% vs 91.6%, p=0.03) and had significantly longer length of stay
      (8.6days IQR 3.7-17.1 vs 4.1days IQR 1.0-10.5, p<0.01). Patients treated at urban
      teaching hospitals were more likely to receive an EEG than patients treated at
      urban non-teaching and rural hospitals (p<0.01). The rate of EEG in survivors of
      cardiac arrest increased from 1.03% in 2006 to 2.16% in 2012, a relative increase
      of 110% (p<0.02). The median time to performance of an EEG was 1.6days IQR 0.33
      4.53 days. CONCLUSION: EEG is performed on approximately 2% of patients who
      suffer cardiac arrest in the United States. The treatment hospital and patient
      characteristics of those who received an EEG different from those who did not.

PMID- 27886949
TI  - Why Do Chilean Women Choose to Have or Not Have Pap Tests?
AB  - OBJECTIVE: To describe the perceptions of Chilean women about why women choose to
      have or not have Pap test screening. DESIGN: Qualitative research using content
      analysis according to Krippendorf. SETTING: Four urban health clinics in
      Santiago, Chile. PARTICIPANTS: Fifty-seven Chilean women. METHODS: Audiotaped
      focus groups. RESULTS: Six themes emerged: Reasons that make it difficult for
      women to schedule appointments, Characteristics of health professionals that make
      it difficult to have a Pap test, Characteristics of the test that are barriers to
      having a Pap test, The relationship of the test with cancer, Family context, and
      Each woman's personal characteristics. CONCLUSION: Primary health care providers
      play an important role in promoting adherence to cervical cancer screening.
      Nurses should proactively address women's perceptions and knowledge about
      screening and openly and uniformly discuss the importance and benefits of Pap
      test screening.

PMID- 27886950
TI  - The Elegance of Structure.

PMID- 27886951
TI  - Endovascular Colorectal Adenocarcinoma Metastasis.

PMID- 27886952
TI  - Complex Inferior Vena Cava Filter Retrieval Complicated by Migration of Filter
      Fragment into the Aorta and Subsequent Distal Embolization.
AB  - In 2005, a 48-year-old man with a spinal cord injury had an inferior vena cava
      filter placed for recurrent deep vein thrombosis and pulmonary embolism. He was
      referred for filter retrieval after a computed tomography scan demonstrated caval
      stenosis and 2 fractured filter arms, 1 in a pulmonary artery and 1 penetrating
      into the retroperitoneum and impinging on the aorta. During retrieval, 1 arm was
      inadvertently advanced into the aorta, and embolization of the arm occurred to
      the left profunda femoris artery. It was subsequently retrieved. This is the
      first reported case to the authors' knowledge of migration and embolization of a
      filter fragment into the systemic arterial system.

PMID- 27886953
TI  - Flipping the Filter: Forceps Retrieval of a Left Common Iliac Vein Denali Filter
      through the Left Common Femoral Vein.

PMID- 27886954
TI  - Venous Access Site Closures Using the VASCADE Vascular Closure System.
AB  - This single-center, retrospective study describes using the VASCADE Vascular
      Closure System (Cardiva Medical, Inc, Santa Clara, California) to close 32 venous
      access sites in 21 consecutive patients (11 females; 10 males; age 45 y +/- 19)
      after catheter-directed interventions. Sheath sizes were 5-10 F (8.7 F +/- 1.7).
      Hemostasis was achieved in 30 of 32 deployments (93.8%). Complications were
      observed after 6 of 32 procedures, including 5 minor events in 4 patients and 1
      major event in 1 patient which was likely unrelated to device deployment. The
      VASCADE device efficaciously closes venotomies after deep venous procedures, but
      further studies comparing it with manual compression are required to define its
      optimal use.

PMID- 27886955
TI  - Iatrogenic Internal Mammary Arteriovenous Fistula.

PMID- 27886956
TI  - Methyl Methacrylate Mimicking a Retained Guide Wire.

PMID- 27886957
TI  - Ultrasound-Guided Percutaneous Microwave Ablation of Parathyroid Adenoma.

PMID- 27886958
TI  - Hepatic Artery Embolization for Hepatic Rupture in HELLP Syndrome.

PMID- 27886959
TI  - Can Aprons Be Properly Evaluated for Their Protective Quality without In-House
      Validation?

PMID- 27886961
TI  - Letter to the Editor.

PMID- 27886960
TI  - Re: Better Outcomes if Percutaneous Drainage Is Used Early and Proactively in the
      Course of Necrotizing Pancreatitis.

PMID- 27886962
TI  - Re: Safety and Efficacy of Doxorubicin Drug-Eluting Embolic Chemoembolization of
      Hepatocellular Carcinoma Supplied by Extrahepatic Collateral Arteries.

PMID- 27886963
TI  - Letters to the Editor.

PMID- 27886964
TI  - Endocrine Treatment Is Still the Main Option in the Management of Metastatic
      Breast Cancer Patients with Liver-Dominant Metastases.

PMID- 27886966
TI  - Erratum

PMID- 27886965
TI  - Letter To The Editor.

PMID- 27886967
TI  - The "Independent" Plastic Surgery Match: Analysis of Changes in Recent Years and
      Applicant Preferences.
AB  - BACKGROUND: The number of surgical applicants to "independent" plastic surgery
      programs has drastically decreased. However, the competitiveness of recent
      applicants relative to previous years has not been assessed. The purpose of this
      study was to analyze the characteristics of recent "independent" applicants and
      to obtain their preferences regarding the match. METHODS: A 25-question survey
      was distributed to 97 applicants of the 2012 "independent" match. The survey
      consisted of questions regarding demographics, academic qualifications, interview
      results, match results, program characteristic preferences, interview
      preferences, and future career plans. RESULTS: A total of 62 applicants
      responded; 71% male, 82% US medical graduates, 94% general surgery residents, and
      76% in university programs. Three-quarters had >=2 publications and 29% in
      plastic surgery journals. Applicants most commonly attended 11 to 13 interviews,
      and 31% got their top choice. Mean rank list position matched was 2.7. Out of 10
      program selection criteria, overall training quality and geographic location were
      most important to applicants. Difficulty of on-call responsibilities and research
      opportunities were least important. Applicants interested in university-based
      practice had a significantly higher interest in research (p = 0.003). Most prefer
      one-on-one interviews with 5 sessions being ideal. Two-thirds would prefer
      regional coordination of interviews. Half were undecided about fellowship, and
      most were undecided about subspecialty of greatest interest. University
      affiliated (39%) and university-based (33%) were the most commonly envisioned
      future practices. CONCLUSION: The profile of "independent" plastic surgery
      applicants has not changed much in recent years. When selecting a program,
      applicants are looking for the best overall operative training above all else
      with little regard for difficulty of on-call responsibilities or ability to do
      research. Applicants are still very moldable in their preference of future career
      plans with the majority possessing an early interest in academic-related
      practices.

PMID- 27886968
TI  - Defining Communication Improvement Needs in General Surgery: An Analysis of
      Pages, Communications, Patterns, and Content??>.
AB  - OBJECTIVE: To describe patterns of pages communication to general surgery (GS)
      residents, identify the need for and develop strategies to improve
      interprofessional communication. DESIGN: Retrospective cohort study. SETTING:
      General surgery (GS) service at a tertiary care academic institution, Sunnybrook
      Health Sciences Centre, in Toronto, Ontario, Canada. PARTICIPANTS: All pages sent
      to GS residents over 4 weeks at an academic institution. Timing, training level
      of receiver and content of pages were captured. RESULTS: Communication priority
      was assigned by 2 independent reviewers-low (121+ min), medium (31-120min), high
      (6-30min), and immediate (0-5min) priority. Overall, 2 independent reviewers
      analyzed pages' content through an inductive process, and generated themes. Of
      2025 pages retrieved, 963 (47.5%) contained exclusively a call back number. A
      median of 74 pages per day (range: 43-116) were received, with median page
      interval of 9.4 minutes (range: 0-640). Junior residents received 79.5% of pages.
      Timing of the pages was 43.9% weekday shift, 31.8% weeknight shift, and 24.3%
      weekend call. Communication priority was deemed low for 35.4% of pages, medium
      for 32.3%, high for 12.4%, and immediate for 0.7%. Content analysis of 1062 pages
      generated 5 major themes: nonurgent medical issue (54.0%), administrative
      (15.3%), communication (13.5%), emergencies (4.8%), and GS consultation requests
      (4.0%). Priority and content of pages varied according to training level and page
      timing. CONCLUSIONS: Pages to GS residents were frequent and most often of low
      priority. They were seldom related to urgent medical matters. Education and new
      communication strategies are warranted to reduce low priority pages.

PMID- 27886970
TI  - Surgical Residency Recruitment-Opportunities for Improvement.
AB  - INTRODUCTION: The Association of Program Directors in Surgery convened a panel
      during Surgical Education Week 2016 to discuss the current state of the general
      surgery residency application process and to review alternative ways to evaluate
      the suitability of each applicant to a residency program. METHODS/RESULTS: Over
      40,000 applicants registered for the National Resident Matching Program's 2016
      Main Residency Match. General Surgery had 2345 applicants for 1241 categorical
      postgraduate year (PGY)-1 positions, and 1239 of those positions were filled when
      the matching algorithm was processed. Program Directors reported that only 33% of
      applications received an in-depth review, and 62% were rejected with minimal
      review. Eventually (after all applications had been reviewed), only 13% of
      applicants were invited to interview. CONCLUSIONS: There are several
      opportunities for improvement within the current application process. These
      included standardized letter of recommendation and personal statements,
      refinement of the interview process, and recalibration of the Medical Student
      Performance Evaluation.

PMID- 27886969
TI  - A Pilot Study to Gauge Effectiveness of Standardized Patient Scenarios in
      Assessing General Surgery Milestones.
AB  - PURPOSE: Some General Surgery Milestones can be difficult to assess in
      traditional clinical settings and especially difficult to assess in junior
      residents. The purpose of this pilot study was to METHODS: A total of 9
      categorical interns participated in a comprehensive, 4-module, SP scenario
      designed to evaluate and manage right upper quadrant pain. SP checklist scores
      (SP%) were converted to Milestone-equivalent scores for direct comparison (SP-C).
      Milestone scores were analyzed from 3 different sources: SP, faculty (FAC), and
      CCC. Interns completed course evaluations at the end of each session. Spearman's
      rho was used to determine correlations. Wilcoxon signed rank tests were used to
      test for differences between scores from different sources. RESULTS: Individual
      intern Milestone scores from the 3 sources (SP-C, FAC, and CCC) did not
      correlate. All 7 mean Milestone scores from SPs were significantly higher than
      from FAC and CCC. FAC and CCC scores were statistically equivalent except for
      Systems-Based Practice 1 (SBP1) and Patient Care 3 (PC3) where CCC scores were
      significantly higher than FAC. Mean SP% scores for PC1 were significantly lower
      than for PROF1, MK1, MK2, and ICS1 (p < 0.05). Interns felt the modules were
      moderately to very useful. CONCLUSIONS: Developing an SP scenario for Milestones
      evaluation is feasible. SPs, faculty observers, and CCC each use different data
      to provide a unique source of Milestone assessment. SP scenarios may be ideally
      suited to assess specific resident strengths and weaknesses and provide
      individualized feedback, thus augmenting traditional evaluations. Additional SP
      scenarios, assessing a broader range of skills and Milestones, are advisable for
      more reliable estimates of resident performance.

PMID- 27886971
TI  - The Feasibility of Real-Time Intraoperative Performance Assessment With SIMPL
      (System for Improving and Measuring Procedural Learning): Early Experience From a
      Multi-institutional Trial.
AB  - PURPOSE: Intraoperative performance assessment of residents is of growing
      interest to trainees, faculty, and accreditors. Current approaches to collect
      such assessments are limited by low participation rates and long delays between
      procedure and evaluation. We deployed an innovative, smartphone-based tool, SIMPL
      (System for Improving and Measuring Procedural Learning), to make real-time
      intraoperative performance assessment feasible for every case in which surgical
      trainees participate, and hypothesized that SIMPL could be feasibly integrated
      into surgical training programs. METHODS: Between September 1, 2015 and February
      29, 2016, 15 U.S. general surgery residency programs were enrolled in an
      institutional review board-approved trial. SIMPL was made available after 70% of
      faculty and residents completed a 1-hour training session. Descriptive and
      univariate statistics analyzed multiple dimensions of feasibility, including
      training rates, volume of assessments, response rates/times, and dictation rates.
      The 20 most active residents and attendings were evaluated in greater detail.
      RESULTS: A total of 90% of eligible users (1267/1412) completed training.
      Further, 13/15 programs began using SIMPL. Totally, 6024 assessments were
      completed by 254 categorical general surgery residents (n = 3555 assessments) and
      259 attendings (n = 2469 assessments), and 3762 unique operations were assessed.
      There was significant heterogeneity in participation within and between programs.
      Mean percentage (range) of users who completed >=1, 5, and 20 assessments were
      62% (21%-96%), 34% (5%-75%), and 10% (0%-32%) across all programs, and 96%, 75%,
      and 32% in the most active program. Overall, response rate was 70%, dictation
      rate was 24%, and mean response time was 12 hours. Assessments increased from 357
      (September 2015) to 1146 (February 2016). The 20 most active residents each
      received mean 46 assessments by 10 attendings for 20 different procedures.
      CONCLUSIONS: SIMPL can be feasibly integrated into surgical training programs to
      enhance the frequency and timeliness of intraoperative performance assessment. We
      believe SIMPL could help facilitate a national competency-based surgical training
      system, although local and systemic challenges still need to be addressed.

PMID- 27886972
TI  - The Resident-Run Minor Surgery Clinic: A Pilot Study to Safely Increase Operative
      Autonomy.
AB  - OBJECTIVE: General surgery training has evolved to align with changes in work
      hour restrictions, supervision regulations, and reimbursement practices. This has
      culminated in a lack of operative autonomy, leaving residents feeling
      inadequately prepared to perform surgery independently when beginning fellowship
      or practice. A resident-run minor surgery clinic increases junior resident
      autonomy, but its effects on patient outcomes have not been formally established.
      This pilot study evaluated the safety of implementing a resident-run minor
      surgery clinic within a university-based general surgery training program.
      DESIGN: Single institution case-control pilot study of a resident-run minor
      surgery clinic from 9/2014 to 6/2015. Rotating third-year residents staffed the
      clinic once weekly. Residents performed operations independently in their own
      procedure room. A supervising attending surgeon staffed each case prior to
      residents performing the procedure and viewed the surgical site before wound
      closure. Postprocedure patient complications and admissions to the hospital
      because of a complication were analyzed and compared with an attending control
      cohort. SETTING: Massachusetts General Hospital General in Boston, MA; an
      academic tertiary care general surgery residency program. PARTICIPANTS: Ten third
      year general surgery residents. RESULTS: Overall, 341 patients underwent a total
      of 399 procedures (110 in the resident clinic vs. 289 in the attending clinic).
      Minor surgeries included soft tissue mass excision (n = 275), abscess incision
      and drainage (n = 66), skin lesion excision (n = 37), skin tag removal (n = 15),
      and lymph node excision (n = 6). There was no significant difference in the
      overall rate of patients developing a postprocedure complication within 30 days
      (3.6% resident vs. 2.8% attending; p = 0.65); which persisted on multivariate
      analysis. Similar findings were observed for the rate of hospital admission
      resulting from a complication. Resident evaluations overwhelmingly supported the
      rotation, citing increased operative autonomy as the greatest strength.
      CONCLUSIONS: Implementation of a resident-run minor surgery clinic is a safe and
      effective method to increase trainee operative autonomy. The rotation is well
      suited for mid-level residents, as it provides an opportunity for realistic self
      evaluation and focused learning that may enhance their operative experience
      during senior level rotations.

PMID- 27886973
TI  - Using the ACGME Milestones for Resident Self-Evaluation and Faculty Engagement.
AB  - BACKGROUND: Since July 2014 General Surgery residency programs have been required
      to use the Accreditation Council for Graduate Medical Education milestones twice
      annually to assess the progress of their trainees. We felt this change was a
      great opportunity to use this new evaluation tool for resident self-assessment
      and to furthermore engage the faculty in the educational efforts of the program.
      METHODS: We piloted the milestones with postgraduate year (PGY) II and IV
      residents during the 2013/2014 academic year to get faculty and residents
      acquainted with the instrument. In July 2014, we implemented the same protocol
      for all residents. Residents meet with their advisers quarterly. Two of these
      meetings are used for milestones assessment. The residents perform an independent
      self-evaluation and the adviser grades them independently. They discuss the
      evaluations focusing mainly on areas of greatest disagreement. The faculty member
      then presents the resident to the clinical competency committee (CCC) and the
      committee decides on the final scores and submits them to the Accreditation
      Council for Graduate Medical Education website. We stored all records anonymously
      in a MySQL database. We used Anova with Tukey post hoc analysis to evaluate
      differences between groups. We used intraclass correlation coefficients and
      Krippendorff's alpha to assess interrater reliability. RESULTS: We analyzed
      evaluations for 44 residents. We created scale scores across all Likert items for
      each evaluation. We compared score differences by PGY level and raters (self,
      adviser, and CCC). We found highly significant increases of scores between most
      PGY levels (p < 0.05). There were no significant score differences per PGY level
      between the raters. The interrater reliability for the total score and 6
      competency domains was very high (ICC: 0.87-0.98 and alpha: 0.84-0.97). Even
      though this milestone evaluation process added additional work for residents and
      faculty we had very good participation (93.9% by residents and 92.9% by faculty)
      and feedback was generally positive. CONCLUSION: Even though implementation of
      the milestones has added additional work for general surgery residency programs,
      it has also opened opportunities to furthermore engage the residents in
      reflection and self-evaluation and to create additional venues for faculty to get
      involved with the educational process within the residency program. Using the
      adviser as the initial rater seems to correlate closely with the final CCC
      assessment. Self-evaluation by the resident is a requirement by the RRC and the
      milestones seem to be a good instrument to use for this purpose. Our early
      assessment suggests the milestones provide a useful instrument to track trainee
      progression through their residency.

PMID- 27886975
TI  - In vitro metabolic engineering of bioelectricity generation by the complete
      oxidation of glucose.
AB  - The direct generation of electricity from the most abundant renewable sugar,
      glucose, is an appealing alternative to the production of liquid biofuels and
      biohydrogen. However, enzyme-catalyzed bioelectricity generation from glucose
      suffers from low yields due to the incomplete oxidation of the six-carbon
      compound glucose via one or few enzymes. Here, we demonstrate a synthetic ATP-
      and CoA-free 12-enzyme pathway to implement the complete oxidation of glucose in
      vitro. This pathway is comprised of glucose phosphorylation via polyphosphate
      glucokinase, NADH generation catalyzed by glucose 6-phosphate dehydrogenase
      (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH), electron transfer from NADH
      to the anode, and glucose 6-phosphate regeneration via the non-oxidative pentose
      phosphate pathway and gluconeogenesis. The faraday efficiency from glucose to
      electrons via this pathway was as high as 98.8%, suggesting the generation of
      nearly 24 electrons per molecule of glucose. The generated current density was
      greatly increased from 2.8 to 6.9mAcm-2 by replacing a low-activity G6PDH with a
      high-activity G6PDH and introducing a new enzyme, 6-phosphogluconolactonase,
      between G6PDH and 6PGDH. These results suggest the great potential of high-yield
      bioelectricity generation through in vitro metabolic engineering.

PMID- 27886974
TI  - Evaluating Coding Accuracy in General Surgery Residents' Accreditation Council
      for Graduate Medical Education Procedural Case Logs.
AB  - INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME)
      case log captures resident operative experience based on Current Procedural
      Terminology (CPT) codes and is used to track operative experience during
      residency. With increasing emphasis on resident operative experiences, coding is
      more important than ever. It has been shown in other surgical specialties at
      similar institutions that the residents' ACGME case log may not accurately
      reflect their operative experience. What barriers may influence this remains
      unclear. As the only objective measure of resident operative experience, an
      accurate case log is paramount in representing one's operative experience. This
      study aims to determine the accuracy of procedural coding by general surgical
      residents at a single institution. METHODS: Data were collected from 2
      consecutive graduating classes of surgical residents' ACGME case logs from 2008
      to 2014. A total of 5799 entries from 7 residents were collected. The CPT codes
      entered by residents were compared to departmental billing records submitted by
      the attending surgeon for each procedure. Assigned CPT codes by institutional
      American Academy of Professional Coders certified abstract coders were considered
      the "gold standard." A total of 4356 (75.12%) of 5799 entries were identified in
      billing records. Excel 2010 and SAS 9.3 were used for analysis. In the event of
      multiple codes for the same patient, any match between resident codes and billing
      record codes was considered a "correct" entry. A 4-question survey was
      distributed to all current general surgical residents at our institution for
      feedback on coding habits, limitations to accurate coding, and opinions on ACGME
      case log representation of their operative experience. RESULTS: All 7 residents
      had a low percentage of correctly entered CPT codes. The overall accuracy
      proportion for all residents was 52.82% (range: 43.32%-60.07%). Only 1 resident
      showed significant improvement in accuracy during his/her training (p = 0.0043).
      The survey response rate was 100%. Survey results indicated that inability to
      find the precise code within the ACGME search interface and unfamiliarity with
      available CPT codes were by far the most common perceived barriers to accuracy.
      Survey results also indicated that most residents (74%) believe that they code
      accurately most of the time and agree that their case log would accurately
      represent their operative experience (66.6%). CONCLUSION: This is the first study
      to evaluate correctness of residents' ACGME case logs in general surgery. The
      degree of inaccuracy found here necessitates further investigation into the
      etiology of these discrepancies. Instruction on coding practices should also
      benefit the residents after graduation. Optimizing communication among attendings
      and residents, improving ACGME coding search interface, and implementing
      consistent coding practices could improve accuracy giving a more realistic view
      of residents' operative experience.

PMID- 27886976
TI  - Airway and serum adipokines after allergen and diesel exposure in a controlled
      human crossover study of atopic adults.
AB  - Adipokines are mediators released from adipose tissue. These proteins are
      regarded as active elements of systemic and pulmonary inflammation, whose
      dysregulation can alter an individual's risk of developing allergic lung
      diseases. Despite this knowledge, adipokine responses to inhaled stimuli are
      poorly understood. We sought to measure serum and lung adiponectin, leptin, and
      resistin in an atopic adult study population following exposure to allergen and
      diesel exhaust (DE). Two types of lung samples including bronchoalveolar lavage
      (BAL) and bronchial wash (BW), and a time course of serum samples, were collected
      from the 18 subjects who participated in the randomized, double-blinded
      controlled human study. The two crossover exposure triads in this study were
      inhaled DE and filtered air each followed by instilled allergen or saline. Serum
      and lung adipokine responses to these exposures were quantified using enzyme
      linked immunosorbent assay. Allergen significantly increased adiponectin and
      leptin in BAL, and adiponectin in the BW 48 hours after exposure. Serum leptin
      and resistin responses were not differentially affected by exposure, but varied
      over time. Coexposure with DE and allergen revealed significant correlations
      between the adiponectin/leptin ratio and FEV1 changes and airway responsiveness
      measures. Changes in lung and serum adipokines in response to allergen exposure
      were identified in the context of a controlled exposure study. Coexposure
      identified a potentially protective role of adiponectin in the lung. This
      response was not observed in those with baseline airway hyper-responsiveness, or
      after allergen exposure alone. The clinical relevance of this potentially
      adaptive adipokine pattern warrants further study.

PMID- 27886977
TI  - Can Submandibular Tracheal Intubation Be an Alternative to Tracheotomy During
      Surgery for Major Maxillofacial Fractures?
AB  - PURPOSE: During surgery for major maxillofacial fractures, orotracheal intubation
      can interfere with some surgical procedures and nasal intubation can be
      contraindicated or impossible. That is why tracheotomy is presented as a
      solution, although it carries a relatively high incidence of complications. In
      this study, the use of submandibular tracheal intubation is basically evaluated
      as an alternative to tracheotomy in such circumstances. MATERIALS AND METHODS:
      This prospective study was performed in patients undergoing surgery for major
      maxillofacial fractures in which oral intubation and/or nasal intubation have
      been unsuitable, impossible, or contraindicated. The technique of submandibular
      intubation was assessed intraoperatively and in the postoperative period. The
      outcomes and complications are presented. RESULTS: The study included 26 patients
      aged between 14 and 57 years. All patients had mandibular fractures, with 19
      midface fractures (73.1%), 11 nasal bone fractures (42.3%), 10 zygomatic bone
      fractures (38.5%), 9 naso-orbito-ethmoidal fractures (34.6%), and 9 frontobasilar
      fractures (34.6%). The procedure time ranged from 5 to 12 minutes (mean, 7
      minutes 4.6 seconds). Delayed extubation was performed in 15 cases (57.7%) in
      which the tube was left in place for a period ranging from 8 to 50 hours (mean,
      30 hours 24 minutes). The technique has proved to be straightforward and
      satisfactory. A postoperative superficial infection occurred in 2 patients,
      whereas hypertrophic scars occurred in another 2 patients. CONCLUSIONS:
      Submandibular endotracheal intubation is straightforward, safe, and quick to
      carry out. It can be an alternative to tracheotomy as it allows operative
      techniques and postoperative airway protection without the risks and side effects
      of tracheotomy.

PMID- 27886978
TI  - In Reply.

PMID- 27886979
TI  - Focusing on the Effectiveness of Prophylactic Antibiotics to Prevent Prosthetic
      Joint Infection Caused by Dental Treatment.

PMID- 27886980
TI  - Alopecia Areata in an Adolescent With Inflammatory Bowel Disease.

PMID- 27886981
TI  - A Computer Adaptive Measure of Delay Discounting.
AB  - Delay discounting has been linked to important behavioral, health, and social
      outcomes, including academic achievement, social functioning and substance use,
      but thoroughly measuring delay discounting is tedious and time consuming. We
      develop and consistently validate an efficient and psychometrically sound
      computer adaptive measure of discounting. First, we develop a binary search-type
      algorithm to measure discounting using a large international data set of 4,190
      participants. Using six independent samples ( N = 1,550), we then present
      evidence of concurrent validity with two standard measures of discounting and a
      measure of discounting real rewards, convergent validity with addictive behavior,
      impulsivity, personality, survival probability; and divergent validity with time
      perspective, life satisfaction, age and gender. The new measure is considerably
      shorter than standard questionnaires, includes a range of time delays, can be
      applied to multiple reward magnitudes, shows excellent concurrent, convergent,
      divergent, and discriminant validity-by showing more sensitivity to effects of
      smoking behavior on discounting.

PMID- 27886983
TI  - Trial of novel leukaemia drug is stopped for second time after two more deaths.

PMID- 27886982
TI  - Impact of Norepinephrine Weight-Based Dosing Compared With Non-Weight-Based
      Dosing in Achieving Time to Goal Mean Arterial Pressure in Obese Patients With
      Septic Shock.
AB  - BACKGROUND: Currently, a lack of standardization exists in norepinephrine dosing
      units, the first-line vasopressor for septic shock. Timely achievement of goal
      mean arterial pressure (MAP) is dependent on optimal vasopressor dosing.
      OBJECTIVE: To determine if weight-based dosing (WBD) of norepinephrine leads to
      earlier time to goal MAP compared with non-WBD in obese patients with septic
      shock. METHODS: This was a retrospective, multicenter cohort study. Patients had
      a body mass index (BMI) >=30 kg/m2 and received norepinephrine for septic shock
      with either a non-WBD strategy (between December 2009 and January 2013) or WBD
      strategy (between January 2013 and December 2015). The primary outcome was time
      to goal MAP. Secondary outcomes were norepinephrine duration, dose requirements,
      and development of treatment-related complications. RESULTS: A total of 287
      patients were included (WBD 144; non-WBD 143). There was no difference in median
      time to goal MAP (WBD 58 minutes, interquartile range [IQR] = 16.8-118.5, vs non
      WBD 60 minutes, IQR = 17.5-193.5; P = 0.28). However, there was a difference in
      median cumulative norepinephrine dose (WBD 12.6 mg, IQR = 4.9-45.9, vs non-WBD
      10.5 mg, IQR = 3.9-25.6; P = 0.04) and time to norepinephrine discontinuation
      (WBD 33 hours, IQR = 15-69, vs non-WBD 27 hours, IQR = 12-51; P = 0.03). There
      was no difference in rates of atrial fibrillation (WBD 15.3% vs non-WBD 23.7%; P
      = 0.07) or mortality (WBD 23.6% vs non-WBD 23.1%; P = 0.92). CONCLUSION: WBD of
      norepinephrine does not achieve time to goal MAP earlier in obese patients with
      septic shock. However, WBD may lead to higher norepinephrine cumulative dose
      requirements and prolonged time until norepinephrine discontinuation.

PMID- 27886984
TI  - The Need for Forest Decontamination: For the Recovery of Fukushima.

PMID- 27886986
TI  - Decontamination and Recovery of a Nuclear Facility to Allow Continued Operation.
AB  - A power supply failure caused a loss of power to key ventilation systems in an
      operating nuclear facility. The in-cell depression was lost, which led to an
      egress of activity through prepared areas and into the normal operating areas.
      After an initial programme of radiological monitoring to quantify and categorise
      the activity in the operating areas, a plan was developed for the decontamination
      and remediation of the plant. The scope of the recovery plan was substantial and
      featured several key stages. The contamination was almost entirely 137Cs,
      reflecting the alpha:beta/gamma ratio for the facility. In addition to the
      physical remediation work, several administrative controls were introduced such
      as new local rules, safety signage to indicate abnormal radiological conditions
      in certain areas and training of the decontamination teams. All areas of plant,
      which were contaminated, were returned to normal access arrangements and the
      plant was successfully returned to full operational capability, <12 months from
      the date of the event.

PMID- 27886985
TI  - Efficacy of Lens Protection Systems: Dependency on Different Cranial CT Scans in
      The Acute Stroke Setting.
AB  - To evaluate the dose-reduction potential with different lens protectors for
      patients undergoing cranial computed tomography (CT) scans. Eye lens dose was
      assessed in vitro (alpha-Al2O3:C thermoluminescence dosemeters) using an Alderson
      Rando phantom(r) in cranial CT protocols at different CT scanners (SOMATOM
      Definition-AS+(r)(CT1) and SOMATOM-Definition-Flash(r) (CT2)) using two different
      lens-protection systems (Somatex(r) (SOM) and Medical Imaging Systems(r) (MIS)).
      Summarised percentage of the transmitted photons: (1) CT1 (a) unenhanced CT (nCT)
      with gantry angulation: SOM = 103%, MIS = 111%; (2) CT2 (a) nCT without gantry
      angulation: SOM = 81%, MIS = 91%; (b) CT angiography (CTA) with automatic dose
      modulation technique: SOM = 39%, MIS = 74%; (c) CTA without dose-modulation
      technique: SOM = 22%, MIS = 48%; (d) CT perfusion: SOM = 44%, MIS = 69%. SOM
      showed a higher dose-reduction potential than MIS maintaining equal image
      quality. Lens-protection systems are most effective in CTA protocols without dose
      reduction techniques. Lens-protection systems lower the average eye lens dose
      during CT scans up to 1/3 (MIS) and 2/3 (SOM), respectively, if the eye lens is
      exposed to the direct beam of radiation. Considering both the CT protocol and the
      material of lens protectors, they seem to be mandatory for reducing the radiation
      exposure of the eye lens.

PMID- 27886987
TI  - INTEGRATED OPERATIONAL DOSIMETRY SYSTEM AT CERN.
AB  - CERN, the European Organization for Nuclear Research, upgraded its operational
      dosimetry system in March 2013 to be prepared for the first Long Shutdown of
      CERN's facilities. The new system allows the immediate and automatic checking and
      recording of the dosimetry data before and after interventions in radiation
      areas. To facilitate the analysis of the data in context of CERN's approach to As
      Low As Reasonably Achievable (ALARA), this new system is interfaced to the
      Intervention Management Planning and Coordination Tool (IMPACT). IMPACT is a web
      based application widely used in all CERN's accelerators and their associated
      technical infrastructures for the planning, the coordination and the approval of
      interventions (work permit principle). The coupling of the operational dosimetry
      database with the IMPACT repository allows a direct and almost immediate
      comparison of the actual dose with the estimations, in addition to enabling the
      configuration of alarm levels in the dosemeter in function of the intervention to
      be performed.

PMID- 27886988
TI  - LIFETIME LUNG CANCER RISKS ASSOCIATED WITH INDOOR RADON EXPOSURE BASED ON VARIOUS
      RADON RISK MODELS FOR CANADIAN POPULATION.
AB  - This study calculates and compares the lifetime lung cancer risks associated with
      indoor radon exposure based on well-known risk models in the literature; two risk
      models are from joint studies among miners and the other three models were
      developed from pooling studies on residential radon exposure from China, Europe
      and North America respectively. The aim of this article is to make clear that the
      various models are mathematical descriptions of epidemiologically observed real
      risks in different environmental settings. The risk from exposure to indoor radon
      is real and it is normal that variations could exist among different risk models
      even when they were applied to the same dataset. The results show that lifetime
      risk estimates vary significantly between the various risk models considered
      here: the model based on the European residential data provides the lowest risk
      estimates, while models based on the European miners and Chinese residential
      pooling with complete dosimetry give the highest values. The lifetime risk
      estimates based on the EPA/BEIR-VI model lie within this range and agree
      reasonably well with the averages of risk estimates from the five risk models
      considered in this study.

PMID- 27886990
TI  - Radiation Protection Studies for Medical Particle Accelerators using Fluka Monte
      Carlo Code.
AB  - Radiation protection (RP) in the use of medical cyclotrons involves many aspects
      both in the routine use and for the decommissioning of a site. Guidelines for
      site planning and installation, as well as for RP assessment, are given in
      international documents; however, the latter typically offer analytic methods of
      calculation of shielding and materials activation, in approximate or idealised
      geometry set-ups. The availability of Monte Carlo (MC) codes with accurate up-to
      date libraries for transport and interaction of neutrons and charged particles at
      energies below 250 MeV, together with the continuously increasing power of modern
      computers, makes the systematic use of simulations with realistic geometries
      possible, yielding equipment and site-specific evaluation of the source terms,
      shielding requirements and all quantities relevant to RP at the same time. In
      this work, the well-known FLUKA MC code was used to simulate different aspects of
      RP in the use of biomedical accelerators, particularly for the production of
      medical radioisotopes. In the context of the Young Professionals Award, held at
      the IRPA 14 conference, only a part of the complete work is presented. In
      particular, the simulation of the GE PETtrace cyclotron (16.5 MeV) installed at
      S. Orsola-Malpighi University Hospital evaluated the effective dose distribution
      around the equipment; the effective number of neutrons produced per incident
      proton and their spectral distribution; the activation of the structure of the
      cyclotron and the vault walls; the activation of the ambient air, in particular
      the production of 41Ar. The simulations were validated, in terms of physical and
      transport parameters to be used at the energy range of interest, through an
      extensive measurement campaign of the neutron environmental dose equivalent using
      a rem-counter and TLD dosemeters. The validated model was then used in the design
      and the licensing request of a new Positron Emission Tomography facility.

PMID- 27886989
TI  - U.S. Department of Defense Multiple-Parameter Biodosimetry Network.
AB  - The U.S. Department of Defense (USDOD) service members are at risk of exposure to
      ionizing radiation due to radiation accidents, terrorist attacks and national
      defense activities. The use of biodosimetry is a standard of care for the triage
      and treatment of radiation injuries. Resources and procedures need to be
      established to implement a multiple-parameter biodosimetry system coupled with
      expert medial guidance to provide an integrated radiation diagnostic system to
      meet USDOD requirements. Current USDOD biodosimetry capabilities were identified
      and recommendations to fill the identified gaps are provided. A USDOD Multi
      parametric Biodosimetry Network, based on the expertise that resides at the Armed
      Forces Radiobiology Research Institute and the Naval Dosimetry Center, was
      designed. This network based on the use of multiple biodosimetry modalities would
      provide diagnostic and triage capabilities needed to meet USDOD requirements.
      These are not available with sufficient capacity elsewhere but could be needed
      urgently after a major radiological/nuclear event.

PMID- 27886991
TI  - RADIATION DOSE FOR PEDIATRIC AND YOUNG ADULT CT: A SURVEY TO ESTABLISH AGE-BASED
      REFERENCE LEVELS OF 2015-2016 IN KOREA.
AB  - To assess the doses delivered to pediatric patients during computed tomography
      (CT) examinations of the brain, chest, high-resolution lung and abdomen, and to
      establish diagnostic reference levels (DRLs) for various age groups in Korea.
      Dose survey was done to the 19 hospitals performing CT on children, addressing
      the scan parameters, volume CT dose index (CTDIvol) and dose length product
      (DLP). Per five age group (0, 1, 2-5, 6-10, 11-17 y of age), the proposed DRLs
      for brain, chest, high-resolution lung and abdomen CT are, respectively, in terms
      of CTDIvol: 18, 23, 26, 31, 36 mGy; 2, 3, 4, 6, 8 mGy; 2, 3, 4, 5, 7 mGy; 3, 4,
      5, 6, 9 mGy; and in terms of DLP: 260, 350, 420, 500, 620 mGy*cm; 50, 80, 100,
      170, 340 mGy*cm; 30, 40, 60, 90, 280 mGy*cm; 70, 80, 200, 300, 500 mGy*cm.
      Compared with published DRLs our suggestion for pediatric CT dose is the lower
      end. However, an optimization process should be initiated to reduce the spread in
      patient dose among hospitals despite same CT protocols shown in the study. A
      major element of this process should be the establishment of institution
      performance standard and the use of built DRLs.

PMID- 27886992
TI  - Characteristics of The Narrow Spectrum Beams Used in the Secondary Standard
      Dosimetry Laboratory at the Lebanese Atomic Energy Commission.
AB  - The Secondary Standard Dosimetry Laboratory at the Lebanese Atomic Energy
      Commission has different calibration methods for various types of dosimeters used
      in industrial, military and medical fields. The calibration is performed using
      different beams of X-rays (low and medium energy) and Gamma radiation delivered
      by a Cesium 137 source. The Secondary Standard Dosimetry laboratory in charge of
      calibration services uses different protocols for the determination of high and
      low air kerma rate and for narrow and wide series. In order to perform this
      calibration work, it is very important to identify all the beam characteristics
      for the different types of sources and qualities of radiation. The following work
      describes the methods used for the determination of different beam
      characteristics and calibration coefficients with their uncertainties in order to
      enhance the radiation protection of workers and patient applications in the
      fields of medical diagnosis and industrial X-ray. All the characteristics of the
      X-ray beams are determined for the narrow spectrum series in the 40 and 200 keV
      range where the inherent filtration, the current intensity, the high voltage, the
      beam profile and the total uncertainty are the specific characteristics of these
      X-ray beams. An X-ray software was developed in order to visualize the reference
      values according to the characteristics of each beam.

PMID- 27886993
TI  - Consideration of the Protection Curtain's Shielding Ability after Identifying the
      Source of Scattered Radiation in the Angiography.
AB  - To decrease radiation exposure to medical staff performing angiography, the dose
      distribution in the angiography was calculated in room using the particle and
      heavy ion transport code system (PHITS), which is based on Monte Carlo code, and
      the source of scattered radiation was confirmed using a tungsten sheet by
      considering the difference shielding performance among different sheet
      placements. Scattered radiation generated from a flat panel detector, X-ray tube
      and bed was calculated using the PHITS. In this experiment, the source of
      scattered radiation was identified as the phantom or acrylic window attached to
      the X-ray tube thus, a protection curtain was placed on the bed to shield against
      scattered radiation at low positions. There was an average difference of 20%
      between the measured and calculated values. The H*(10) value decreased after
      placing the sheet on the right side of the phantom. Thus, the curtain could
      decrease scattered radiation.

PMID- 27886994
TI  - Development of Northeast Asia Nuclear Power Plant Accident Simulator.
AB  - A conclusion from the lessons learned after the March 2011 Fukushima Daiichi
      accident was that Korea needs a tool to estimate consequences from a major
      accident that could occur at a nuclear power plant located in a neighboring
      country. This paper describes a suite of computer-based codes to be used by
      Korea's nuclear emergency response staff for training and potentially operational
      support in Korea's national emergency preparedness and response program. The
      systems of codes, Northeast Asia Nuclear Accident Simulator (NANAS), consist of
      three modules: source-term estimation, atmospheric dispersion prediction and dose
      assessment. To quickly assess potential doses to the public in Korea, NANAS
      includes specific reactor data from the nuclear power plants in China, Japan and
      Taiwan. The completed simulator is demonstrated using data for a hypothetical
      release.

PMID- 27886995
TI  - Cosmic Radiation Exposure of Future Hypersonic Flight Missions.
AB  - Cosmic radiation exposure in air traffic grows with flight altitude, geographical
      latitude and flight time. For future high-speed intercontinental point-to-point
      travel, the trade-off between reduced flight time and enhanced dose rate at
      higher flight altitudes is investigated. Various representative (partly)
      hypersonic cruise missions are considered and in dependence on solar activity the
      integral route dose is calculated for envisaged flight profiles and trajectories.
      Our results are compared to those for corresponding air connections served by
      present day subsonic airliners. During solar maximum, we find a significant
      reduction in route dose for all considered high-speed missions compared to the
      subsonic reference. However, during solar minimum, comparable or somewhat larger
      doses result on transpolar trajectories with (partly) hypersonic cruise at Mach
      5. Both solar activity and routing are hence found to determine, whether
      passengers can profit from shorter flight times in terms of radiation exposure,
      despite of altitude-induced higher dose rates. Yet, aircrews with fixed number of
      block hours are always subject to larger annual doses, which in the considered
      cases take values up to five times the reference. We comment on the implications
      of our results for route planning and aviation decision-making in the absence of
      radiation shielding solutions.

PMID- 27886996
TI  - A Comparison of Remediation After The Chernobyl and Fukushima Daiichi Accidents.
AB  - Extensive remediation was conducted on contaminated landscapes after the
      Chernobyl accident in 1986 and the Fukushima Daiichi accident in 2011. A
      comparison is made of a range of different features relevant to each accident
      including the characteristics of the contamination and the landscapes affected,
      the radiological criteria, the designation of areas to be remediated and the
      remediation measures adopted.

PMID- 27886998
TI  - Wilfrid T Fothergill.

PMID- 27886997
TI  - Using Stable Free Radicals to Obtain Unique and Clinically Useful Data In Vivo in
      Human Subjects.
AB  - This paper attempts to: (1) provide a critical overview of the challenges and
      opportunities to extend electron paramagnetic resonance (EPR) into practical
      applications in human subjects, based on EPR measurements made in vivo; (2)
      summarize the clinical applications of EPR for improving treatments in cancer,
      wound healing and diabetic care, emphasizing EPR's unique capability to measure
      tissue oxygen repeatedly and with particular sensitivity to hypoxia and (3)
      summarize the capabilities of in vivo EPR to measure radiation dose for triage
      and medical guidance after a large-scale radiation exposure. The conclusion is
      that while still at a relatively early stage of its development and availability,
      clinical applications of EPR already have demonstrated significant value and the
      field is likely to grow in both the extent of its applications and its impact on
      significant problems.

PMID- 27886999
TI  - Oliver Guy Dodge.

PMID- 27887000
TI  - Oral cancer rates rise by two thirds.

PMID- 27887001
TI  - Douglas Stewart Robbie.

PMID- 27887002
TI  - Longitudinal Predictions of Depression Symptoms Using the Activation and
      Avoidance Subscales of the Japanese Behavioral Activation for Depression Scale
      Short Form.
AB  - The Behavioral Activation for Depression Scale-Short Form (BADS-SF) is a
      questionnaire containing two subscales: Activation and Avoidance and was
      developed to measure changes in client behavior over the course of behavioral
      activation therapy. This study examines whether the subscales of the Japanese
      BADS-SF predict the future development of depression. Japanese university
      students ( N = 129) completed the BADS-SF and the Center for Epidemiologic
      Studies Depression Scale (CES-D) at the baseline and second test conducted eight
      weeks later, with no intervention in between. Multiple regression analyses
      revealed that baseline avoidance scores predicted the scores of CES-D during the
      second test, after controlling for baseline CES-D and the other BADS-SF subscale
      scores, but the relationship of the Activation subscale with the CES-D scores was
      not significant. Therefore, the results indicate that the avoidance scale
      predicts the occurrence of symptoms of depression.

PMID- 27887003
TI  - Philip Markman.

PMID- 27887004
TI  - Janet Anne Peters.

PMID- 27887005
TI  - Patrick Guy Houghton.

PMID- 27887006
TI  - The Perceived Impact of Trauma-Focused Research on Forensic Psychiatric Patients
      With Lifetime Victimization Histories.
AB  - This study examined the perceived costs, benefits, and motivations for
      participating in individual trauma-focused interviews among forensic psychiatric
      patients ( N = 74). The majority of our participants were male, and 100% endorsed
      adverse childhood experiences (e.g., abuse, neglect) or exposure to potentially
      traumatic events (e.g., assault). Levels of posttraumatic avoidance (41.9%),
      reexperiencing (59.5%), and increased arousal (51.3%) were high. In line with
      previous studies, our findings suggest an overall positive research experience in
      this sample. In spite of extensive histories of lifetime victimization we did not
      find an association between victimization, posttraumatic symptomatology, and a
      negative research experience. Our findings suggest that participation in trauma
      focused research is not only possible with, but also potentially beneficial for
      forensic patients.

PMID- 27887007
TI  - Clinical commissioning groups will be rated on sepsis care.

PMID- 27887009
TI  - Continuous Performance Test Is Sensitive to a Single Methylphenidate Challenge in
      Preschool Children With ADHD.
AB  - OBJECTIVE: There is a lack of evidence-based diagnostic paradigms and
      personalized interventions for preschoolers with ADHD. This study aimed to
      evaluate the performance of preschoolers diagnosed with ADHD on a continuous
      performance test (CPT) before and after a single methylphenidate (MPH) challenge.
      METHOD: The Test of Variables of Attention (TOVA)-a CPT-was administered to 61
      preschoolers (5.64 +/- 0.69 years; 74% boys) with ADHD before and after a single
      MPH challenge (0.3 or 0.5 mg/kg). Baseline TOVA performance was correlated with
      Conners' Rating Scales (CRS) and compared with post-MPH TOVA performance.
      RESULTS: A high rate of omission errors and several significant correlations
      between TOVA values and CRS scores were found at baseline. A single MPH
      administration improved TOVA performance significantly and was well tolerated.
      CONCLUSION: TOVA assessment may assist in the evaluation of the effect of MPH in
      preschoolers with ADHD and may help in planning interventions for them.

PMID- 27887010
TI  - Technical note: rapid, large-volume resuscitation at resuscitative thoracotomy by
      intra-cardiac catheterization.
AB  - An emergency thoracotomy may be life-saving by achieving four goals: (i)
      releasing cardiac tamponade, (ii) controlling haemorrhage, (iii) allowing access
      for internal cardiac massage and (iv) clamping the descending aorta to isolate
      circulation to the upper torso in damage control surgery. We theorize that a new
      goal should be achieving rapid, large-volume fluid resuscitation and we describe
      a technique to achieve this.

PMID- 27887008
TI  - Can Sluggish Cognitive Tempo Be Distinguished From ADHD Inattention in Very Young
      Children? Evidence From a Sample of Korean Preschool Children.
AB  - OBJECTIVE: This study evaluated whether sluggish cognitive tempo (SCT) is
      separable from ADHD-inattention (IN) and uniquely associated with internalizing
      dimensions in preschool children in South Korea. METHOD: Mothers of 172 preschool
      children (ages 4-6 years; 52% girls) rated children's SCT, ADHD-IN, ADHD
      hyperactivity/impulsivity (HI), oppositional defiant disorder (ODD), aggression,
      emotional reactivity, anxiety/depression, somatic complaints, withdrawal, and
      sleep problems. RESULTS: Eight of 10 SCT symptoms showed convergent and
      discriminant validity with ADHD-IN. ADHD-IN remained significantly positively
      associated with ADHD-HI, ODD, and aggressive behavior after controlling for SCT,
      whereas SCT was no longer positively associated with these externalizing
      behaviors after controlling for ADHD-IN. Both SCT and ADHD-IN were uniquely
      associated with greater emotionally reactivity, anxiety/depression, and
      withdrawal. Only SCT was uniquely associated with somatic complaints, and only
      ADHD-IN was uniquely associated with sleep problems. CONCLUSION: Findings
      replicate results with children and adolescents, thus expanding evidence for the
      validity of SCT in early development.

PMID- 27887011
TI  - Large primary leiomyoma causing progressive cervical deformity.
AB  - Leiomyomas are benign smooth tumors that rarely affect the neck area. Complete
      surgical resection is the treatment of choice. Here, we describe a 13-year-old
      girl with a large leiomyoma of the neck, which increased in size after incomplete
      resection. The tumor caused progressive cervical kyphotic deformity, difficulty
      breathing and severe malnourishment. The tumor was resected successfully in a
      second surgery, and the patient is stable after 3 years of follow-up.
      Histopathologically, the tumor was consistent with leiomyoma and showed strong
      reactivity to specific smooth muscle markers, such as desmin and caldesmon. This
      is the second reported case demonstrating massive growth of a leiomyoma, with
      emphasis on complete resection from the beginning.

PMID- 27887012
TI  - Epididymal papillary cystadenocarcinoma metastasising to the testis in a patient
      with infertility managed with Onco-microTeSE.
AB  - Papillary cystadenomas of the epididymis are known to occur in association with
      Von Hippel-Lindau (VHL) disease. The development of a papillary
      cystadenocarcinoma, its malignant counterpart, is rare with only a few sporadic
      cases reported in the literature. Metastatic deposits are exceedingly uncommon;
      in fact, only a single case report has documented metastases to the paraureteral
      region, but metastases to the testis have never been reported. A 43-year-old
      gentleman with VHL disease presented with non-obstructive azoospermia, a right
      epididymal mass, and an atrophic surgically corrected undescended left testis.
      The epididymal mass was reported as a papillary cystadenocarcinoma on biopsy. The
      patient was managed with a radical inguinal orchidectomy and bench microTeSE with
      successful sperm retrieval. Metastatic papillary cystadenocarcinoma of the
      epididymis to the testis has never been previously reported. This case was
      managed by radical orchidectomy and subsequent onco-microTeSE, allowing safe
      oncological treatment and optimal fertility preservation.

PMID- 27887013
TI  - Severe cervical spondylotic myelopathy with complete neurological and
      neuroradiological recovery within a month after surgery.
AB  - Cervical spondylotic myelopathy is a complex syndrome evolving in the presence of
      degenerative changes. The choice of care and prognostic factors are
      controversial. The use of appropriate surgical technique is very important.
      Posterior approach may be chosen when pathology is present dorsally and/or in the
      presence of neutral to lordotic alignment. Anterior approach is the golden
      standard in patients with kyphosis and/or stenosis due to ventral lesions, even
      with three or more affected levels. A 67-year-old man presented with progressive
      weakness and clumsiness (mJOA: 5; Nurick: 4). An anterior discectomy,
      osteophytectomy and bilateral foraminotomy of the C4-C5; C5-C6; C6-C7 were
      performed. Polyether-Ether-Ketone spacers and a titanium plate were placed. The
      patient was mobilized 3-hour post-surgery and was released the following day.
      Medicament therapy and a neck-conditioning program were prescribed. Clinical
      examinations were normal within a month. Magnetic resonance imaging showed no
      traces of the preoperatively registered intramedullary focal T2 hyper-intensity.

PMID- 27887014
TI  - Intra-abdominal myositis ossificans in an asymptomatic patient during closure of
      a Hartmann's colostomy.
AB  - Intra-abdominal myositis ossificans, also known as heterotopic mesenteric
      ossification, defines the formation of bone-like lesions inside the abdominal
      cavity. It is a rare medical condition, usually following abdominal surgery or
      trauma. A 55-year-old male presented for closure of a Hartmann's colostomy,
      created 6 months ago because of sigmoid adenocarcinoma. Intraoperative findings
      consisted of an elongated bone-like lesion attached on the peritoneum and
      protruding inside the abdominal cavity, while two more stiff calcified nodules
      were found in the mesocolon. All lesions were excised. The presence of a hard
      consistency sigmoid stump led to cancelation of the operation. Heterotopous bone
      formation constitutes a challenging surgical condition, since its clinical
      presentation is innocuous and repetitive surgery acts a stimuli for additional
      bone creation. Computed tomography scan plays a major role in its diagnosis,
      while nonsteroidal anti-inflammatory drugs and cimetidine are helpful in
      preventing further recurrence of the disease.

PMID- 27887015
TI  - Uncommon cause for ileocolic fistulation and caecal perforation following
      multiple magnet ingestion in an adult.
AB  - Non-accidental ingestion of foreign bodies rarely occurs in adults. We report a
      case of multiple magnet ingestion in an adult with learning difficulties to
      highlight the associated abdominal complications. Multiple magnets may not pass
      through the gastrointestinal tract spontaneously and approach considerations
      should differ from those who had ingested an isolated magnet or other foreign
      bodies.

PMID- 27887016
TI  - Inferior vena caval filter strut perforation causing intramural duodenal
      haematoma.
AB  - We present a case of intramural duodenal haematoma caused by inferior vena caval
      (IVC) filter strut perforation requiring innovative open and endovascular
      retrieval. A 32-year-old woman presents in shock with dull epigastric pain and
      non-bilious vomiting. She had previously had an IVC filter for deep venous
      thrombosis and pulmonary embolism. Computed tomography demonstrated strut
      perforation into the second part of the duodenum, causing intramural haematoma
      and duodenal obstruction. Laparotomy facilitated evacuation of the duodenal
      haematoma, while the IVC filter was retrieved by endovascular means. Causes of
      duodenal haematoma include blunt trauma, haematologic malignancy, coagulopathy,
      percutaneous or endoscopic procedures, pancreatic pathology, peptic ulcer disease
      and aortoenteric fistula. Duodenal haematoma is rare and is usually managed
      conservatively or by percutaneous drainage. While this patient had a typical
      presentation, IVC filter strut perforation has not been described in the
      literature as a cause for duodenal haematoma.

PMID- 27887017
TI  - Massive seminoma presenting with inguinal lymph node metastases only.
AB  - Seminomatous germ cell tumours characteristically affect men in their second-to
      fourth decades, presenting as a testicular mass. Metastases when present are
      usually seen in para-aortic lymph nodes. These tumours are difficult to diagnose
      clinically and histologically when the presentation is unusual. We describe a
      seminoma presenting in a 61-year-old male as an inguinal mass with associated
      lymphadenopathy resembling lymphoma. Past medical history included ipsilateral
      cryptorchidism and orchidopexy. The tumour responded well to conventional
      chemotherapy.This case illustrates a possible diagnostic pitfall and that germ
      cell tumours should be included in the differential diagnosis of tumours
      presenting in the groin.

PMID- 27887018
TI  - Case report: imaging the clinical course of FOPE-a cause of adolescent knee pain.
AB  - Focal periphyseal oedema (FOPE) is a rare MRI finding associated with pain in
      adolescent patients with very few reported cases. We present a case of FOPE in a
      13-year-old girl and the only follow-up imaging available for an isolated
      presentation of this condition.This article describes a clinical course that
      correlates well with the imaging obtained. This article describes a clinical
      course that correlates well with the imaging obtained.

PMID- 27887019
TI  - First case of penile metastasis following abdominoperineal resection with VRAM
      flap reconstruction.
AB  - Penile metastases are rare in colorectal cancer. We report the first case of such
      a recurrence in a patient who had undergone an extralevator abdominoperineal
      resection with vertical rectus abdominis myocutaneous flap perineal
      reconstruction. The patient was treated with curative intent by total penectomy.

PMID- 27887020
TI  - Gastric glomus tumor.
AB  - Gastric glomus tumors are rare, mesenchymal neoplasms, generally described as
      benign and account for nearly 1% of all gastrointestinal soft tissue tumors. The
      most common gastrointestinal site of involvement is the stomach, particularly the
      antrum. Gastric glomus tumors are submucosal tumors that lack specific clinical
      and endoscopic characteristics, and are often mistaken for the more common
      gastrointestinal stromal tumors. A 62-year-old Caucasian female presented with
      shortness of breath and a persistent cough. Clinical workup revealed a mass in
      the upper abdomen. After endoscopic ultrasound and fine needle aspiration raised
      concerns for cancer, the patient elected to proceed with exploratory laparotomy.
      A local resection was performed at the time of surgery. Pathologic and
      immunohistochemical findings following surgical resection were consistent with a
      gastric glomus tumor. Consideration of gastric glomus tumors in the differential
      diagnosis may optimize the chance for a more accurate preoperative diagnosis and
      targeted surgical intervention.

PMID- 27887021
TI  - An unusual presentation of a rare disease: posterior reversible encephalopathy
      syndrome following abdominal sepsis.
AB  - Posterior reversible encephalopathy syndrome (PRES) is an unusual disease of
      unknown incidence and cause. There are a wide range of associated, predisposing
      medical causes to include pregnancy, renal failure, immunosuppressive medication
      administration and hypertension. The diagnosis is made following the radiographic
      identification of characteristic vasogenic edema in the setting of neurologic
      impairment. A significant portion of patients will have long-term, if not
      permanent, sequelae of the disease. We present a patient who developed PRES
      following a hemicolectomy that was complicated by an anastomotic leak. She went
      on to a complete recovery following surgical treatment of the leak and supportive
      care.

PMID- 27887022
TI  - Case report: successful open resection of a symptomatic giant liver haemangioma
      during the second trimester of pregnancy.
AB  - Liver haemangiomas are consistently reported to be the commonest benign liver
      tumours and are most often incidental findings in asymptomatic individuals. Large
      lesions can become symptomatic, spontaneously rupture or result in a consumptive
      coagulopathy known as Kasabach-Merrit Syndrome. It is believed that the female
      sex hormones, particularly oestrogen, have an influence on haemangioma
      development and growth. The optimal management of large haemangiomas during the
      hyperoestrogenic state of pregnancy is poorly described in the current
      literature. To our knowledge, we describe only the second case of a giant hepatic
      haemangioma resection during pregnancy.

PMID- 27887023
TI  - A case of primary intracardiac yolk sac tumour with extracardiac extension.
AB  - Primary cardiac tumour is a rare entity as secondaries in the heart are more
      common. A 2-year-old child was having repeated respiratory tract infection with
      poor oral intake and poor activity for 3 months. His symptoms progressed from New
      York Heart Association (NYHA) Class II to IV. On evaluation he had an
      intracardiac mass with extracardiac extension. Emergency tumour excision under
      deep hypothermic circulatory arrest was performed with provisional diagnosis of
      sarcoma. But Serum markers, histopathological examination and
      immunohistochemistry confirmed diagnosis of yolk sac tumour. Postoperative
      recovery was uneventful and the child was receiving adjuvant chemotherapy.
      Extensive literature review revealed only four cases of primary intracardiac yolk
      sac tumour published till date. Our case report is unique, in that intracardiac
      tumour had extracardiac extension by infiltration through right atrial wall.
      Previous four reports mention purely intracardiac mass.

PMID- 27887024
TI  - Insulinoma or non-insulinoma pancreatogenous hypoglycemia? A diagnostic dilemma.
AB  - Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia
      in adults. An alternate etiology, non-insulinoma pancreatogenous hypoglycemia
      (NIPH), is rare. Clinically, NIPH is characterized by postprandial
      hyperinsulinemic hypoglycemia, negative 72-h fasts, negative preoperative
      localization studies for insulinoma and positive selective arterial calcium
      infusion tests. Histologically, diffuse islet hyperplasia with increased number
      and size of islet cells is present and confirms the diagnosis. Differentiating
      NIPH from occult insulinoma preoperatively is challenging. Partial pancreatectomy
      is the procedure of choice; however, recurrence of symptoms, although less
      debilitating, occurs commonly. Medical management with diazoxide, verapamil and
      octreotide can be used for persistent symptoms. Ultimately, near-total or total
      pancreatectomy may be necessary. We report a case of a 67-year-old male with
      hypoglycemia in whom preoperative workup, including computerized tomography
      abdomen, suggested insulinoma, but whose final diagnosis on pathology was NIPH
      instead.

PMID- 27887025
TI  - Design and expression of a chimeric vaccine candidate for avian necrotic
      enteritis.
AB  - Necrotic enteritis is an economically important disease of poultry mainly caused
      by Clostridium perfringens The bacteria release multiple toxins of which NetB,
      alpha toxin and TpeL have been reported to play important roles in pathogenicity
      and/or severity of the disease. In this study, the sequence of clostridial toxins
      NetB, alpha toxin and TpeL were analyzed using bioinformatics tools to determine
      protein domains with high immunogenicity factor. Several chimeric trivalent
      proteins consisting of the immunogenic regions of the three toxins were designed
      and evaluated. The separate regions were fused together using rigid linkers.
      Based on a modeled tertiary structure, a proper combination was selected and
      expressed in a bacterial host (Escherichia coli) and successfully purified. The
      expression of the chimeric protein was further verified by western blotting. The
      ability of the immunized serum in recognizing each individual subunit of the
      chimeric protein was also examined. Circular dichroism was used to evaluate the
      predicted secondary structure of the chimeric protein. In vitro potency test
      demonstrated that the serum from a rabbit immunized with the chimeric protein is
      able to partially neutralize Alpha toxin, hence the construct can potentially be
      used as a vaccine against C. perfringens.

PMID- 27887026
TI  - Chaetomium thermophilum formate dehydrogenase has high activity in the reduction
      of hydrogen carbonate (HCO3 -) to formate.
AB  - While formate dehydrogenases (FDHs) have been used for cofactor recycling in
      chemoenzymatic synthesis, the ability of FDH to reduce CO2 could also be utilized
      in the conversion of CO2 to useful products via formate (HCOO-). In this study,
      we investigated the reduction of CO2 in the form of hydrogen carbonate (HCO3-) to
      formate by FDHs from Candida methylica (CmFDH) and Chaetomium thermophilum
      (CtFDH) in a NADH-dependent reaction. The catalytic performance with HCO3- as a
      substrate was evaluated by measuring the kinetic rates and conducting
      productivity assays. CtFDH showed a higher efficiency in converting HCO3- to
      formate than CmFDH, whereas CmFDH was better in the oxidation of formate. The pH
      optimum of the reduction was at pH 7-8. However, the high concentrations of HCO3-
      reduced the reaction rate. CtFDH was modeled in the presence of HCO3- showing
      that it fits to the active site. The active site setting for hydride transfer in
      CO2 reduction was modeled. The hydride donated by NADH would form a favorable
      contact to the carbon atom of HCO3-, resulting in a surplus of electrons within
      the molecule. This would cause the complex formed by hydrogen carbonate and the
      hydride to break into formate and hydroxide ions.

PMID- 27887027
TI  - Expansion of the substrate range of the gentisate 1,2-dioxygenase from
      Corynebacterium glutamicum for the conversion of monohydroxylated benzoates.
AB  - The gentisate 1,2-dioxygenases (GDOs) from Corynebacterium glutamicum and various
      other organisms oxidatively cleave the aromatic nucleus of gentisate (2,5
      dihydroxybenzoate), but are not able to convert salicylate (2-hydroxybenzoate).
      In contrast, the alpha-proteobacterium Pseudaminobacter salicylatoxidans
      synthesises an enzyme ('salicylate dioxygenase', SDO) which cleaves gentisate,
      but also (substituted) salicylate(s). Sequence comparisons showed that the SDO
      belongs to a group of GDOs mainly originating from Gram-positive bacteria which
      also include the GDO from C. glutamicum ATCC 13032. The combination of sequence
      comparisons with previously performed structural and mutational analyses of the
      SDO allowed to identify an amino acid residue (Ala112) which might prevent the
      oxidation of (substituted) salicylate(s) by the GDO from C. glutamicum Therefore,
      the relevant mutation (Ala->Gly) was introduced into the GDO from C. glutamicum
      The GDO variant obtained gained the ability to oxidise salicylate and several
      other monohydroxylated substrates. In order to screen a broader range of enzyme
      variants a chromogenic assay was developed which allowed the detection of
      bacterial colonies converting salicylate. The applicability of this test system
      was proven by screening a set of GDO variants obtained by saturation mutagenesis
      at different positions. This demonstrated that also GDO variants carrying the
      mutations Ala112->Ser, Ala112->Ile and Ala112->Asp converted salicylate.

PMID- 27887028
TI  - Influence of urbanity on perception of mental illness stigma: a population based
      study in urban and rural Hanoi, Vietnam.
AB  - BACKGROUND AND AIMS: To examine, for the first time in Vietnam, whether urbanity
      of respondents among other socio-demographic factors affects the public
      perception of stigma attached to persons with mental illness in Hanoi. METHODS: A
      general population-based survey was carried out in 2013 in the greater Hanoi
      area. The perception of stigma attached to people with mental illness was
      elicited using Link's perceived discrimination and devaluation scale (PDDS)
      carried out in Vietnamese language. The survey sample (n = 806) was stratified
      for gender, urban/rural location, age, household size and marital status, in
      accordance with the 2013 Vietnamese census. RESULTS: Comparing the total score of
      the PDDS and its single items, we found less perceived stigma and discrimination
      among the rural population of Hanoi and in respondents who reported religious
      attainment to either Buddhism or Christianity. Logistic regression analyses found
      no significant influences of gender, age, household size or marital status
      regarding the perceived stigma toward persons with mental illness. CONCLUSION:
      Less negative perception of stigma attached to persons with mental illness that
      was observed among the rural population in the Hanoi area may be interpreted in
      the light of possibly more demanding living conditions in modern urban Vietnam
      with less opportunities for mentally ill patients and points toward a dynamic
      interaction with rapidly changing living conditions in Asian megacities.

PMID- 27887029
TI  - Circulating Humorous Antitobacco Videos on Social Media.
AB  - We investigated whether exposure to same humorous antitobacco videos via
      different types of social media platforms and contexts (health vs. humor)
      influences individual's health risk perceptions, attitudes, and behavioral
      intents. An experiment with a 2 (social media types: YouTube and Facebook) * 2
      (message contexts: health-focused and humor-focused contexts) factorial design
      was conducted. It was found that those who watched the humorous antitobacco
      videos on Facebook in the health-context exhibited a higher level of risk
      perception of smoking, less positive attitude toward smokers, and a higher level
      of intention to avoid smoking in the future than the participants who viewed the
      same videos on YouTube in the health-context or on Facebook in the humor-context.
      These findings provide useful practical guidelines in using social media for
      health communication/promotion. Humorous health promotion messages are best
      circulated on social networking sites such as Facebook accompanied by others'
      support for the given health topic (i.e., in health-contexts).
      Practical/theoretical implications and limitations of the study were further
      discussed in this article.

PMID- 27887030
TI  - Energy and nutrient intakes of Swedish children in relation to consumption of and
      habits associated with school lunch.
AB  - AIMS: School lunches are provided free in Sweden, although some children choose
      not to eat school lunch. The aim of this study was to analyse Swedish children's
      total energy and nutrient intakes on weekdays by the frequency of school lunch
      consumption and to analyse energy and nutrient intakes from school lunches by
      sex. Factors associated with children's school lunch habits were also studied.
      METHODS: Children in grades 2 and 5 ( n=1905) completed a food diary (school
      lunch data available for 1840 children) and the mean energy and nutrient intakes
      per day and per school lunch were calculated. The children also completed
      questions on the frequency of school lunch consumption and school lunch habits.
      Logistic regression was used to assess factors associated with school lunch
      habits. RESULTS: Children who reported eating school lunch every day had
      significantly higher energy and absolute nutrient intakes than children reporting
      eating school lunch less than five times a week, but not standardized for energy.
      Boys had significantly higher energy and absolute nutrient intakes from school
      lunches than girls, but not standardized for energy. Younger children and
      children who liked school lunches had higher odds of eating school lunch every
      day. Children in grade 5, those with a foreign background and those disliking
      school lunches had higher odds of omitting the main lunch component. CONCLUSIONS:
      Regular school lunch consumption was associated with a higher total intake for
      most nutrients, but not a better nutrient density. School lunch habits were
      associated with age, ethnic background and liking school lunches.

PMID- 27887031
TI  - Job mobility and health in the Danish workforce.
AB  - AIMS: The globalized economy has stimulated mobility in the labour market in many
      countries and Denmark has one of the highest rates of mobility between workplaces
      among the OECD countries. This raises the question of the potential health
      effects of mobility and the effect of disease on mobility. METHODS: This study
      was register-based with a longitudinal design using data on the entire Danish
      population in 1992-2006. The data included mobility between employers and
      workplaces and seven different diseases based on admissions to hospital and drug
      prescriptions. RESULTS: After adjusting for relevant confounders, an exposure
      response relationship was seen between mobility and the incidence of ischaemic
      heart disease, stroke, duodenal ulcer, anxiety/depression and, most strongly,
      with alcohol-related disorders. The effects were not very strong, however, with
      odds ratios varying from 1.2 to 1.6. As expected, no effect was seen for
      colorectal cancer. We also found an effect of both somatic and mental disorders
      on mobility, but not for the two cancer types. Mobility did not seem to prevent
      being out of the labour force after diagnosis. CONCLUSIONS: Frequent mobility in
      the labour market increases the risk of cardiovascular disease, common mental
      disorders and alcohol-related disorders and these diagnoses also seem to increase
      the risk of subsequent mobility.

PMID- 27887032
TI  - Provider Perception of Pharmacy Services in the Patient-Centered Medical Home.
AB  - BACKGROUND: Despite the positive data on clinical outcomes, cost savings, and
      provider experience, no study has surveyed providers to evaluate what pharmacy
      services they find to be worthwhile. OBJECTIVE: To determine what clinical,
      cost/access, and educational pharmacy services providers in a patient-centered
      medical home (PCMH) consider worthwhile and the perceived barriers to successful
      pharmacist incorporation. METHODS: A cross-sectional online survey was
      distributed to primary care physicians, nurse practitioners, and physician
      assistants in a PCMH physician group. RESULTS: The survey response rate was 78%.
      Top-tier clinical services were identified as medication counseling,
      reconciliation, adherence assessment, polypharmacy assessment, and drug
      information. Formulary review was the only top-tier cost- or access-related
      service. Top-tier educational services included new black-boxed warnings, drug
      market withdrawals, and new drug reviews. Ninety-one percent of providers were
      comfortable referring to a pharmacist for diabetes medication selection and dose
      titration, but no other disease state eclipsed 75%. More than twice as many
      providers found the pharmacy service to be very or extremely valuable when the
      pharmacist is physically located in the office versus virtual interactions (70%
      vs 34%). CONCLUSION: Top-tier clinical, cost/access, and educational services
      considered worthwhile by providers in a PCMH have been identified. In addition to
      these services, when developing or evaluating a pharmacy service, special
      attention should be paid to provider preference for physical location in the
      office and perceived barriers to the pharmacist availability, concern over
      complex disease management competency and patient confusion as to the role of the
      pharmacist.

PMID- 27887033
TI  - Skin Irritation and Sensitization Potential of Fixed-Dose Combination of
      Diclofenac 1% and Menthol 3% Topical Gel: Results of Two Phase I Patch Studies.
AB  - Phase I, randomized, controlled patch studies were conducted to evaluate skin
      sensitization and irritation potential of a new gel formulation containing 1%
      diclofenac and 3% menthol as a fixed-combination product.In study A, healthy
      volunteers were exposed to 4 test patches containing 1% diclofenac+3% menthol,
      diclofenac, menthol, or placebo gels during an induction (nine 48 to 72-h
      applications) and challenge phase (one 48-h application). Some subjects were re
      challenged to evaluate suspected sensitization. Study B participants underwent 21
      consecutive 24-h patch applications of the 4 treatments from study A, 0.2% sodium
      lauryl sulfate (positive control), 0.9% saline, and a marketed gel (1%
      diclofenac, Voltaren). Application sites were visually scored by blinded
      observers for skin sensitization/irritation.In study A, 77% of participants
      showed minimal erythema and signs of glazing and peeling with 1% diclofenac+3%
      menthol by the end of the induction phase, which diminished during the challenge
      phase. Similar patterns were seen with menthol gel. Only 1 subject exhibited
      possible sensitization to 1% diclofenac+3% menthol. In study B, mean cumulative
      irritation score with 1% diclofenac+3% menthol was significantly higher
      (P<0.0001) vs. reference treatments; however, the positive control failed to
      produce the expected level of irritation. No treatment-related adverse events
      were reported.The sensitization and irritation potential of 1% diclofenac+3%
      menthol was greater than with the reference treatments. Comparison with positive
      control was not possible because it did not produce irritation under
      semiocclusive patch conditions.

PMID- 27887035
TI  - Impact of transgene genome location on gene migration from herbicide-resistant
      wheat (Triticum aestivum L.) to jointed goatgrass (Aegilops cylindrica Host).
AB  - BACKGROUND: Wheat (Triticum aestivum) (ABD) and jointed goatgrass (Aegilops
      cylindrica) (CD) can cross and produce hybrids that can backcross to either
      parent. Such backcrosses can result in progeny with chromosomes and/or chromosome
      segments retained from wheat. Thus, a herbicide resistance gene could migrate
      from wheat to jointed goatgrass. In theory, the risk of gene migration from
      herbicide-resistant wheat to jointed goatgrass is more likely if the gene is
      located on the D genome and less likely if the gene is located on the A or B
      genome of wheat. RESULTS: BC1 populations (jointed goatgrass as a recurrent
      parent) were analyzed for chromosome numbers and transgene transmission rates
      under sprayed and non-sprayed conditions. Transgene retention in the non-sprayed
      BC1 generation for the A, B and D genomes was 84, 60 and 64% respectively. In the
      sprayed populations, the retention was 81, 59 and 74% respectively. CONCLUSION:
      The gene transmission rates were higher than the expected 50% or less under
      sprayed and non-sprayed conditions, possibly owing to meiotic chromosome
      restitution and/or chromosome non-disjunction. Such high transmission rates in
      the BC1 generation negates the benefits of gene placement for reducing the
      potential of gene migration from wheat to jointed goatgrass. (c) 2016 Society of
      Chemical Industry.

PMID- 27887034
TI  - Epicurus and B. F. Skinner: In search of the good life.
AB  - This paper examines similarities in the works of Epicurus, an ancient Greek
      philosopher, and B. F. Skinner, a behavioral psychologist. They both were
      empiricists who argued in favor of the lawfulness of behavior while maintaining
      that random events were included within those laws. They both devoted much effort
      to describing how individuals could live effective, rewarding and pleasurable
      lives. They both emphasized simple and natural pleasures (or reinforcers) and the
      importance of combining personal pleasures with actions that benefit friends and
      community. They both opposed punishment and all aversive measures used by
      governments and religions to control behaviors. And both created utopias: a real
      community, The Garden, where Epicurus lived with his followers, and a fictional
      one, Walden Two, by Skinner. We consider how a combination of the ideas of
      Epicurus and Skinner can contribute to their common goal of helping people to
      live better lives.

PMID- 27887036
TI  - Customized mandibular reconstruction plates improve mechanical performance in a
      mandibular reconstruction model.
AB  - The purpose of this paper was to analyze the biomechanical performance of
      customized mandibular reconstruction plates with optimized strength. The best
      locations for increasing bar widths were determined with a sensitivity analysis.
      Standard and customized plates were mounted on mandible models and mechanically
      tested. Maximum stress in the plate could be reduced from 573 to 393 MPa (-31%)
      by increasing bar widths. The median fatigue limit was significantly greater (p <
      0.001) for customized plates (650 +/- 27 N) than for standard plates (475 +/- 27
      N). Increasing bar widths at case-specific locations was an effective strategy
      for increasing plate fatigue performance.

PMID- 27887037
TI  - Failure of CRP decline within three days of hospitalization is associated with
      poor prognosis of Community-acquired Pneumonia.
AB  - BACKGROUND: C-reactive protein (CRP) is a well-known acute phase protein used to
      monitor the patient's response during treatment in infectious diseases. Mortality
      from Community-acquired Pneumonia (CAP) remains high, particularly in
      hospitalized patients. Better risk prediction during hospitalization could
      improve management and ultimately reduce mortality levels. The aim of this study
      was to evaluate CRP on the 3rd day (CRP3) of hospitalization as a predictor for
      30 days mortality. METHODS: A retrospective multicentre cohort study of adult
      patients admitted with CAP at three Danish hospitals. Predictive associations of
      CRP3 (absolute levels and relative decline) and 30 days mortality were analysed
      using receiver operating characteristics and logistic regression. RESULTS: Eight
      hundred and fourteen patients were included and 90 (11%) died within 30 days. The
      area under the curve for CRP3 level and decline for predicting 30 days mortality
      were 0.64 (0.57-0.70) and 0.71 (0.65-0.76). Risk of death was increased in
      patients with CRP3 level >75 mg/l (OR 2.44; 95%CI 1.36-4.37) and in patients with
      a CRP3 decline <50% (OR 4.25; 95%CI 2.30-7.83). In the multivariate analysis, the
      highest mortality risk was seen in patients who failed to decline by 50%,
      irrespective of the actual level of CRP (OR 7.8; 95%CI 3.2-19.3). Mortality risk
      increased significantly according to CRP decline for all strata of CURB-65 score.
      CONCLUSIONS: CRP responses day 3 is a valuable predictor of 30 days mortality in
      hospitalized CAP patients. Failure to decline in CRP was associated with a poor
      prognosis irrespective of the actual level of CRP or CURB-65.

PMID- 27887039
TI  - Corrigendum.

PMID- 27887038
TI  - AIMS65 score: a new prognostic tool to predict mortality in variceal bleeding.

PMID- 27887040
TI  - In vitro assessment of non-irritant microemulsified voriconazole hydrogel system.
AB  - Research was aimed on microemulsion-based hydrogel for voriconazole. Oleic acid
      and isopropyl myristate as lipid phases; tween 20: tween 80 as surfactants and
      PEG600 as cosurfactant were selected to formulate voriconazole microemulsions.
      The promising microemulsions in terms of zeta potential, pH, viscosity, and drug
      release were selected and developed into hydrogels using carbopol 934. Resulting
      microemulsion-based hydrogel (MBH) of voriconazole were evaluated for in vitro
      diffusion and ex vivo permeation. Antifungal potentials of MBH were assessed
      against selected fungal strains. Optimal MBH formulations, O6 and O8 had
      displayed their antifungal potentials with enlarged zone of inhibition against
      selected fungal strains.

PMID- 27887202
TI  - Serological markers in diagnosis of pediatric inflammatory bowel disease and as
      predictors for early tumor necrosis factor blocker therapy.
AB  - OBJECTIVE: To describe the prevalence of serological markers in newly diagnosed
      treatment-naive pediatric inflammatory bowel disease (IBD), their utility in
      differentiating Crohn's disease (CD), ulcerative colitis (UC) and symptomatic non
      IBD patients and whether serological markers are associated with early TNF
      blocker treatment. MATERIAL AND METHODS: Ninety-six children and adolescents <18
      years, 58 with IBD and 38 symptomatic non-IBD controls were included. At
      diagnosis and after 1-2 years, serological antibodies (anti-Saccharomyces
      cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibody
      (pANCA), flagellin expressed by Clostridial phylum (anti-CBir1), outer membrane
      porin of Escherichia coli (anti-OmpC), Pseudomonas fluorescens-associated
      sequence (anti-I2), CRP, ESR and fecal calprotectin were analyzed. The choice of
      treatment was made at the discretion of the treating pediatrician. RESULTS: Of
      the IBD patients, 20 (36%) and 26 (47%) were positive for ASCA and pANCA compared
      to 3(8%), p < .01 and 10 (27%), p = .04 of the controls. Thirteen (72%) of UC
      patients were pANCA positive, versus 13 (35%) of CD patients (p < .01). None of
      the UC patients was ASCA positive versus 20 (54%) of CD patients (p < .0001).
      Compared to conventionally treated patients, the 18 (49%) TNF blocker treated CD
      patients had higher presence of ASCA (p < .01), lower presence of pANCA (p = .02)
      and higher levels of fecal calprotectin, CRP and ESR at diagnosis. In
      multivariate analyses ASCA and pANCA status, but not CRP, ESR or calprotectin,
      were independently associated with early TNF blocker treatment. CONCLUSIONS: ASCA
      and pANCA status were associated with having IBD and with early TNF blocker
      treatment in CD.

PMID- 27887203
TI  - Contrast enhanced ultrasound features of hepatic cystadenoma and hepatic
      cystadenocarcinoma.
AB  - OBJECTIVE: Hepatic (biliary) cystic tumor (HBCT) is a rare focal cystic liver
      lesion, which has been rarely described in the literature. In our current
      multicenter, retrospective study, we aimed to analyze contrast enhanced
      ultrasound (CEUS) features and its diagnostic performance in histologically
      proved HBCT. MATERIAL AND METHODS: Twenty-three patients with single HBCT were
      retrospectively analyzed. Histologically, 17 (73.9%) were benign hepatic
      (biliary) cystadenoma (HBCA), 6 (26.1%) were hepatic (biliary) cystadenocarcinoma
      (HBCAC). All CEUS examinations were assessed by two independent radiologists in
      consensus. Criteria of CEUS imaging evaluation included the contrast enhancement
      pattern of lesion (hypoenhancing, hyperenhancing, isoenhancing in comparison to
      the surrounding liver parenchyma) during the arterial, portal venous and late
      phases. RESULTS: After injection of ultrasound contrast agents, most of the HBCTs
      (78.3%, 18/23) had typical honeycomb enhancement pattern of the cystic wall,
      septa or mural nodules. Comparing between HBCA and HBCAC, hyperenhancement of the
      honeycomb septa during the arterial phase was more common in HBCA (p = .047).
      However, hypoenhancement during the portal venous and late phases was the
      characteristic of HBCAC (p = .041). CONCLUSIONS: The EFSUMB algorithm for CEUS
      for characterization of solid focal liver lesions is also applicable to HBCT.
      CEUS evaluation can avoid further diagnostic investigations or invasive biopsy
      procedure.

PMID- 27887563
TI  - The trans-generational impact of population density signals on host-parasite
      interactions.
AB  - BACKGROUND: The density of a host population is a key parameter underlying
      disease transmission, but it also has implications for the expression of disease
      through its effect on host physiology. In response to higher densities,
      individuals are predicted to either increase their immune investment in response
      to the elevated risk of parasitism, or conversely to decrease their immune
      capacity as a consequence of the stress of a crowded environment. However, an
      individual's health is shaped by many different factors, including their genetic
      background, current environmental conditions, and maternal effects. Indeed,
      population density is often sensed through the presence of info-chemicals in the
      environment, which may influence a host's interaction with parasites, and also
      those of its offspring. All of which may alter the expression of disease, and
      potentially uncouple the presumed link between changes in host density and
      disease outcomes. RESULTS: In this study, we used the water flea Daphnia magna
      and its obligate bacterial parasite Pasteuria ramosa, to investigate how signals
      of high host density impact on host-parasite interactions over two consecutive
      generations. We found that the chemical signals from crowded treatments induced
      phenotypic changes in both the parental and offspring generations. In the absence
      of a pathogen, life-history changes were genotype-specific, but consistent across
      generations, even when the signal of density was removed. In contrast, the
      influence of density on infected animals depended on the trait and generation of
      exposure. When directly exposed to signals of high-density, host genotypes
      responded differently in how they minimised the severity of disease. Yet, in the
      subsequent generation, the influence of density was rarely genotype-specific and
      instead related to ability of the host to minimise the onset of infection.
      CONCLUSION: Our findings reveal that population level correlations between host
      density and infection capture only part of the complex relationship between
      crowding and the severity of disease. We suggest that besides its role in
      horizontal transmission, signals of density can influence parasite epidemiology
      by modifying mechanisms of resistance across multiple generations, and elevating
      variability via genotype-by-environment interactions. Our results help resolve
      why some studies are able to find a positive correlation between high density and
      resistance, while others uncover a negative correlation, or even no direct
      relationship at all.

PMID- 27887564
TI  - The Drosophila transcriptional network is structured by microbiota.
AB  - BACKGROUND: Resident microorganisms (microbiota) have far-reaching effects on the
      biology of their animal hosts, with major consequences for the host's health and
      fitness. A full understanding of microbiota-dependent gene regulation requires
      analysis of the overall architecture of the host transcriptome, by identifying
      suites of genes that are expressed synchronously. In this study, we investigated
      the impact of the microbiota on gene coexpression in Drosophila. RESULTS: Our
      transcriptomic analysis, of 17 lines representative of the global genetic
      diversity of Drosophila, yielded a total of 11 transcriptional modules of co
      expressed genes. For seven of these modules, the strength of the transcriptional
      network (defined as gene-gene coexpression) differed significantly between flies
      bearing a defined gut microbiota (gnotobiotic flies) and flies reared under
      microbiologically sterile conditions (axenic flies). Furthermore, gene
      coexpression was uniformly stronger in these microbiota-dependent modules than in
      both the microbiota-independent modules in gnotobiotic flies and all modules in
      axenic flies, indicating that the presence of the microbiota directs gene
      regulation in a subset of the transcriptome. The genes constituting the
      microbiota-dependent transcriptional modules include regulators of growth,
      metabolism and neurophysiology, previously implicated in mediating phenotypic
      effects of microbiota on Drosophila phenotype. Together these results provide the
      first evidence that the microbiota enhances the coexpression of specific and
      functionally-related genes relative to the animal's intrinsic baseline level of
      coexpression. CONCLUSIONS: Our system-wide analysis demonstrates that the
      presence of microbiota enhances gene coexpression, thereby structuring the
      transcriptional network in the animal host. This finding has potentially major
      implications for understanding of the mechanisms by which microbiota affect host
      health and fitness, and the ways in which hosts and their resident microbiota
      coevolve.

PMID- 27887565
TI  - Genomic evaluation by including dominance effects and inbreeding depression for
      purebred and crossbred performance with an application in pigs.
AB  - BACKGROUND: Improved performance of crossbred animals is partly due to heterosis.
      One of the major genetic bases of heterosis is dominance, but it is seldom used
      in pedigree-based genetic evaluation of livestock. Recently, a trivariate genomic
      best linear unbiased prediction (GBLUP) model including dominance was developed,
      which can distinguish purebreds from crossbred animals explicitly. The objectives
      of this study were: (1) methodological, to show that inclusion of marker-based
      inbreeding accounts for directional dominance and inbreeding depression in
      purebred and crossbred animals, to revisit variance components of additive and
      dominance genetic effects using this model, and to develop marker-based
      estimators of genetic correlations between purebred and crossbred animals and of
      correlations of allele substitution effects between breeds; (2) to evaluate the
      impact of accounting for dominance effects and inbreeding depression on
      predictive ability for total number of piglets born (TNB) in a pig dataset
      composed of two purebred populations and their crossbreds. We also developed an
      equivalent model that makes the estimation of variance components tractable.
      RESULTS: For TNB in Danish Landrace and Yorkshire populations and their
      reciprocal crosses, the estimated proportions of dominance genetic variance to
      additive genetic variance ranged from 5 to 11%. Genetic correlations between
      breeding values for purebred and crossbred performances for TNB ranged from 0.79
      to 0.95 for Landrace and from 0.43 to 0.54 for Yorkshire across models. The
      estimated correlation of allele substitution effects between Landrace and
      Yorkshire was low for purebred performances, but high for crossbred performances.
      Predictive ability for crossbred animals was similar with or without dominance.
      The inbreeding depression effect increased predictive ability and the estimated
      inbreeding depression parameter was more negative for Landrace than for Yorkshire
      animals and was in between for crossbred animals. CONCLUSIONS: Methodological
      developments led to closed-form estimators of inbreeding depression, variance
      components and correlations that can be easily interpreted in a quantitative
      genetics context. Our results confirm that genetic correlations of breeding
      values between purebred and crossbred performances within breed are positive and
      moderate. Inclusion of dominance in the GBLUP model does not improve predictive
      ability for crossbred animals, whereas inclusion of inbreeding depression does.

PMID- 27887566
TI  - The common redstart as a suitable model to study cuckoo-host coevolution in a
      unique ecological context.
AB  - BACKGROUND: Co-evolutionary arms-races result in spatio-temporally dynamic
      relationships between interacting species, e.g., brood parasites and their avian
      hosts. However, majority of avian co-evolutionary studies are limited to "snap
      shots" of a single breeding season in an open-nesting host. In a long-term study
      (11 breeding seasons), we explored a unique system between the brood parasitic
      common cuckoo (Cuculus canorus) and its host, the common redstart (Phoenicurus
      phoenicurus) which is exceptional among all cuckoo hosts due to being a cavity
      nester. Conditions in cavities are different from open nests, e.g., lower risks
      of predation, more favourable microclimate, increased risks of unsuccessful
      eviction of host offspring by the cuckoo nestling. Different conditions in
      cavities thus can be expected to shape parasite-host coevolution differently from
      what is typically studied in open nesting hosts. RESULTS: In our highly
      parasitised nest-box population (32.5%, n = 569 nests) only 35.7% of cuckoo eggs
      were laid into the nest cup and incubated by redstarts. Host nests shifted
      availability to later into the breeding season from 2006 to 2016 and cuckoos
      followed this trend by also shifting their timing of parasitism. Although
      previous studies revealed that redstarts selectively eject experimental non
      mimetic eggs (desertion was not a specific response to foreign eggs), the hosts
      never ejected naturally-laid cuckoo eggs or cuckoo eggs cross-fostered into
      naturally non-parasitised nests. We solve the long-standing debate about the
      origin of cuckoo eggs found on the nest rim: we gained the first direct video
      recording evidence that eggs found on the nest rim were mislaid by parasites and
      not ejected by hosts. Naturally-parasitised nests were deserted more often
      (18.6%) than control non-parasitized nests (5.6%) or nests artificially
      parasitised by us (1.4%). This suggests that the sight of the laying cuckoo
      female is the primary cue that triggers egg rejection (by desertion) in this
      host. Review of data from this and other study sites (10 populations, n = 853
      experiments) demonstrates high variability in rejection rates and shows that
      populations facing higher parasitism rates reject parasitic eggs with higher
      frequencies. Surprisingly, cuckoo chicks either growing solitarily or with
      redstart chicks did not differ in their fledging success. CONCLUSIONS: We suggest
      that the redstart is an ideal model system to study the flexibility and limits of
      brood parasite-host co-evolution in an extreme ecological setting.

PMID- 27887567
TI  - Fluorescence chromosome banding and FISH mapping in perennial ryegrass, Lolium
      perenne L.
AB  - BACKGROUND: The unambiguous identification of individual chromosomes is a key
      part of the genomic characterization of any species. In this respect, the
      development and application of chromosome banding techniques has revolutionised
      mammalian and especially, human genomics. However, partly because of the
      traditional use of chromosome squash preparations, consistent fluorescence
      banding has rarely been achieved in plants. Here, successful fluorescence
      chromosome banding has been achieved for the first time in perennial ryegrass
      (Lolium perenne), a forage and turf grass with a large genome and a symmetrical
      karyotype with chromosomes that are difficult to distinguish. RESULTS: Based on
      flame-dried chromosome preparations instead of squashes, a simple fluorescence Q
      banding technique using quinacrine mustard, unambiguously identified each
      chromosome and enabled the development of a banded karyotype and ideogram of the
      species. This Q-banding technique was also shown to be compatible with sequential
      FISH mapping enabling labelled genes and molecular markers to be precisely
      assigned to specific cytogenetic bands. A technique for DAPI-banding, which gave
      a similar pattern to Q-banding, was also introduced. This was compatible with
      FISH mapping and was used to anchor a single copy gene from an earlier mapped
      linkage group of L. perenne, thus providing a step towards integration of the
      genetic and cytogenetic maps. CONCLUSIONS: By enabling the allocation of genes
      mapped by other methods to physically identified chromosome positions, this work
      will contribute to a better understanding of genomic structures and functions in
      grasses.

PMID- 27887568
TI  - A new method of finding groups of coexpressed genes and conditions of
      coexpression.
AB  - BACKGROUND: To study a biological phenomenon such as finding mechanism of
      disease, common methodology is to generate the microarray data in different
      relevant conditions and find groups of genes co-expressed across conditions from
      such data. These groups might enable us to find biological processes involved in
      a disease condition. However, more detailed understanding can be made when
      information of a biological process associated with a particular condition is
      obtained from the data. Many algorithms are available which finds groups of co
      expressed genes and associated conditions of co-expression that can help finding
      processes associated with particular condition. However, these algorithms depend
      on different input parameters for generating groups. For real datasets, it is
      difficult to use these algorithms due to unknown values of these parameters.
      RESULTS: We present here an algorithm, clustered groups, which finds groups of co
      expressed genes and conditions of co-expression with minimal input from user. We
      used random datasets to derive a cutoff on the basis of which we filtered the
      resultant groups and showed that this can improve the relevance of obtained
      groups. We showed that the proposed algorithm performs better than other known
      algorithms on both real and synthetic datasets. We have also shown its
      application on a temporal microarray dataset by extracting biclusters and
      biological information hidden in those biclusters. CONCLUSIONS: Clustered groups
      is an algorithm which finds groups of co-expressed genes and conditions of co
      expression using only a single parameter. We have shown that it works better than
      other existing algorithms. It can be used to find these groups in different data
      types such as microarray, proteomics, metabolomics etc.

PMID- 27887570
TI  - MetaMIS: a metagenomic microbial interaction simulator based on microbial
      community profiles.
AB  - BACKGROUND: The complexity and dynamics of microbial communities are major
      factors in the ecology of a system. With the NGS technique, metagenomics data
      provides a new way to explore microbial interactions. Lotka-Volterra models,
      which have been widely used to infer animal interactions in dynamic systems, have
      recently been applied to the analysis of metagenomic data. RESULTS: In this
      paper, we present the Lotka-Volterra model based tool, the Metagenomic Microbial
      Interacticon Simulator (MetaMIS), which is designed to analyze the time series
      data of microbial community profiles. MetaMIS first infers underlying microbial
      interactions from abundance tables for operational taxonomic units (OTUs) and
      then interprets interaction networks using the Lotka-Volterra model. We also
      embed a Bray-Curtis dissimilarity method in MetaMIS in order to evaluate the
      similarity to biological reality. MetaMIS is designed to tolerate a high level of
      missing data, and can estimate interaction information without the influence of
      rare microbes. For each interaction network, MetaMIS systematically examines
      interaction patterns (such as mutualism or competition) and refines the biotic
      role within microbes. As a case study, we collect a human male fecal microbiome
      and show that Micrococcaceae, a relatively low abundance OTU, is highly connected
      with 13 dominant OTUs and seems to play a critical role. MetaMIS is able to
      organize multiple interaction networks into a consensus network for comparative
      studies; thus we as a case study have also identified a consensus interaction
      network between female and male fecal microbiomes. CONCLUSIONS: MetaMIS provides
      an efficient and user-friendly platform that may reveal new insights into
      metagenomics data. MetaMIS is freely available at:
      https://sourceforge.net/projects/metamis/ .

PMID- 27887569
TI  - Immune modulation of CD4+CD25+ regulatory T cells by zoledronic acid.
AB  - BACKGROUND: CD4+CD25+ regulatory T (Treg) cells suppress tumor immunity by
      inhibiting immune cells. Manipulation of Treg cells represents a new strategy for
      cancer treatment. Zoledronic acid (ZA), a nitrogen-containing bisphosphonate,
      inhibits the expression of receptor activator of nuclear factor kappa-B ligand
      (RANKL) on osteoblasts to inhibit osteoclastogenesis. In a mouse model of
      bisphosphonate-related osteonecrosis of the jaw, administration of ZA suppressed
      Treg-cell activity and activated inflammatory Th17 cells. However, the
      interaction between ZA and Treg cells remained unclear. This study investigated
      the immune modulation of Treg cells by ZA. METHODS: Flow cytometry was used to
      analyze the phenotypic and immunosuppressive characteristics of Treg cells
      treated with ZA. Chemotactic migration was evaluated using transwell assays.
      Quantitative real-time PCR (qRT-PCR) was used to investigate the effect of ZA on
      the expression of suppressive molecules by Treg cells. RESULTS: Proliferation of
      isolated Treg cells in culture was inhibited by ZA, although ZA did not induce
      apoptosis. qRT-PCR and flow cytometry showed that ZA significantly downregulated
      the expression of CCR4, CTLA4, PD-1 and RANKL on Treg cells. Chemotactic
      migration and immunosuppressive functions were also significantly attenuated in
      Treg cells pretreated with ZA, and these effects were dose-dependent. Co-culture
      with Treg cells significantly increased the migration rate of breast cancer
      cells, while pretreatment of Treg cells with ZA attenuated this effect.
      CONCLUSIONS: Our findings demonstrated that ZA acted as an immune modulator by
      significantly inhibiting the expansion, migration, immunosuppressive function and
      pro-metastatic ability of Treg cells. Immunomodulation of Treg cells by ZA
      represents a new strategy for cancer therapy.

PMID- 27887571
TI  - LBSizeCleav: improved support vector machine (SVM)-based prediction of Dicer
      cleavage sites using loop/bulge length.
AB  - BACKGROUND: Dicer is necessary for the process of mature microRNA (miRNA)
      formation because the Dicer enzyme cleaves pre-miRNA correctly to generate miRNA
      with correct seed regions. Nonetheless, the mechanism underlying the selection of
      a Dicer cleavage site is still not fully understood. To date, several studies
      have been conducted to solve this problem, for example, a recent discovery
      indicates that the loop/bulge structure plays a central role in the selection of
      Dicer cleavage sites. In accordance with this breakthrough, a support vector
      machine (SVM)-based method called PHDCleav was developed to predict Dicer
      cleavage sites which outperforms other methods based on random forest and naive
      Bayes. PHDCleav, however, tests only whether a position in the shift window
      belongs to a loop/bulge structure. RESULT: In this paper, we used the length of
      loop/bulge structures (in addition to their presence or absence) to develop an
      improved method, LBSizeCleav, for predicting Dicer cleavage sites. To evaluate
      our method, we used 810 empirically validated sequences of human pre-miRNAs and
      performed fivefold cross-validation. In both 5p and 3p arms of pre-miRNAs,
      LBSizeCleav showed greater prediction accuracy than PHDCleav did. This result
      suggests that the length of loop/bulge structures is useful for prediction of
      Dicer cleavage sites. CONCLUSION: We developed a novel algorithm for feature
      space mapping based on the length of a loop/bulge for predicting Dicer cleavage
      sites. The better performance of our method indicates the usefulness of the
      length of loop/bulge structures for such predictions.

PMID- 27887572
TI  - Maternal smoking impacts key biological pathways in newborns through epigenetic
      modification in Utero.
AB  - BACKGROUND: Children exposed to maternal smoking during pregnancy exhibit
      increased risk for many adverse health effects. Maternal smoking influences
      methylation in newborns at specific CpG sites (CpGs). Here, we extend evaluation
      of individual CpGs to gene-level and pathway-level analyses among 1062
      participants in the Norwegian Mother and Child Cohort Study (MoBa) using the
      Illumina 450 K platform to measure methylation in newborn DNA and maternal
      smoking in pregnancy, assessed using the biomarker, plasma cotinine. We used
      novel implementations of bioinformatics tools to collapse epigenome-wide
      methylation data into gene- and pathway-level effects to test whether exposure to
      maternal smoking in utero differentially methylated CpGs in genes enriched in
      biologic pathways. Unlike most pathway analysis applications, our approach allows
      replication in an independent cohort. RESULTS: Data on 485,577 CpGs, mapping to a
      total of 20,199 genes, were used to create gene scores that were tested for
      association with maternal plasma cotinine levels using Sequence Kernel
      Association Test (SKAT), and 15 genes were found to be associated (q < 0.25). Six
      of these 15 genes (GFI1, MYO1G, CYP1A1, RUNX1, LCTL, and AHRR) contained
      individual CpGs that were differentially methylated with regards to cotinine
      levels (p < 1.06 * 10-7). Nine of the 15 genes (FCRLA, MIR641, SLC25A24, TRAK1,
      C1orf180, ITLN2, GLIS1, LRFN1, and MIR451) were associated with cotinine at the
      gene-level (q < 0.25) but had no genome-wide significant individual CpGs (p >
      1.06 * 10-7). Pathway analyses using gene scores resulted in 51 significantly
      associated pathways, which we tested for replication in an independent cohort (q
      < 0.05). Of those 32 replicated in an independent cohort, which clustered into
      six groups. The largest cluster consisted of pathways related to cancer, cell
      cycle, ERalpha receptor signaling, and angiogenesis. The second cluster,
      organized into five smaller pathway groups, related to immune system function,
      such as T-cell regulation and other white blood cell related pathways.
      CONCLUSIONS: Here we use novel implementations of bioinformatics tools to
      determine biological pathways impacted through epigenetic changes in utero by
      maternal smoking in 1062 participants in the MoBa, and successfully replicate
      these findings in an independent cohort. The results provide new insight into
      biological mechanisms that may contribute to adverse health effects from exposure
      to tobacco smoke in utero.

PMID- 27887573
TI  - In-vitro function of upstream visfatin polymorphisms that are associated with
      adverse cardiometabolic parameters in obese children.
AB  - BACKGROUND: Visfatin is an adipokine associated with glucose and lipid
      metabolism. We previously reported two visfatin upstream single nucleotide
      polymorphisms (SNPs), c.-3187G > A (rs11977021) and c.-1537C > T (rs61330082),
      which were in perfect linkage disequilibrium, in a Singaporean cohort of severely
      obese children and are associated with visfatin level and adverse cardiometabolic
      parameters. We aim to functionally characterize the effect of c.-3187G > A and c.
      1537C > T SNPs on basal transcriptional activity. METHODS: A 1.6 kb and 3.7 kb
      upstream promoter region of the visfatin gene was amplified by polymerase chain
      reaction and separately cloned into luciferase reporter vectors. Successful
      clones were transfected into human embryonic kidney (HEK293T) and human breast
      carcinoma (MCF7) cells and in-vitro dual-luciferase assay was performed. 
      Electrophoretic mobility shift assay (  EMSA) was also conducted to examine the
      binding affinity between transcription factors and visfatin promoter sequences.
      RESULTS: Variant promoter with only c.-1537C > T SNP did not show a change in
      transcriptional activity as compared to the wild type. However, variant promoter
      with both c.-3187G > A and c.-1537C > T SNPs showed a statistically significant
      increase of 1.41 fold (p < 0.01) in transcriptional activity. The longer 3.7kbp
      visfatin promoter sequence was also shown to have significantly higher
      transcriptional activity (p < 0.05) as compared to the shorter 1.6kbp visfatin
      promoter. Both c.-3187G > A and c.-1537C > T variants showed an increased binding
      with nuclear protein. DISCUSSION AND CONCLUSIONS: We have demonstrated for the
      first time that visfatin variant promoter with both c.-3187G > A and c.-1537C > T
      SNPs result in an increase in transcriptional activity. This supports our
      previous finding and postulation that these SNPs contribute to elevated visfatin
      levels which may mediate higher triglyceride levels, severe systolic blood
      pressure and severe hypertension in obese children. These SNPs may co-operatively
      affect enhancer or silencer function to regulate transcriptional activity. In
      conclusion, this study shows that upstream visfatin SNPs could potentially affect
      phenotypic outcome in obese children through alteration of circulating visfatin
      level.

PMID- 27887574
TI  - FluxFix: automatic isotopologue normalization for metabolic tracer analysis.
AB  - BACKGROUND: Isotopic tracer analysis by mass spectrometry is a core technique for
      the study of metabolism. Isotopically labeled atoms from substrates, such as
      [13C]-labeled glucose, can be traced by their incorporation over time into
      specific metabolic products. Mass spectrometry is often used for the detection
      and differentiation of the isotopologues of each metabolite of interest. For
      meaningful interpretation, mass spectrometry data from metabolic tracer
      experiments must be corrected to account for the naturally occurring isotopologue
      distribution. The calculations required for this correction are time consuming
      and error prone and existing programs are often platform specific, non-intuitive,
      commercially licensed and/or limited in accuracy by using theoretical
      isotopologue distributions, which are prone to artifacts from noise or unresolved
      interfering signals. RESULTS: Here we present FluxFix ( http://fluxfix.science ),
      an application freely available on the internet that quickly and reliably
      transforms signal intensity values into percent mole enrichment for each
      isotopologue measured. 'Unlabeled' data, representing the measured natural
      isotopologue distribution for a chosen analyte, is entered by the user. This data
      is used to generate a correction matrix according to a well-established
      algorithm. The correction matrix is applied to labeled data, also entered by the
      user, thus generating the corrected output data. FluxFix is compatible with
      direct copy and paste from spreadsheet applications including Excel (Microsoft)
      and Google sheets and automatically adjusts to account for input data dimensions.
      The program is simple, easy to use, agnostic to the mass spectrometry platform,
      generalizable to known or unknown metabolites, and can take input data from
      either a theoretical natural isotopologue distribution or an experimentally
      measured one. CONCLUSIONS: Our freely available web-based calculator, FluxFix (
      http://fluxfix.science ), quickly and reliably corrects metabolic tracer data for
      natural isotopologue abundance enabling faster, more robust and easily accessible
      data analysis.

PMID- 27887575
TI  - The gut microbiota in young and middle-aged rats showed different responses to
      chicken protein in their diet.
AB  - BACKGROUND: Meat protein in the diet has been shown to be beneficial for the
      growth of Lactobacillus in the caecum of growing rats; however, it is unknown
      whether gut microbiota in middle-aged animals have the same responses to meat
      protein diets. This study compared the composition of the gut microbiota between
      young and middle-aged rats after being fed 17.7% chicken protein diet for 14
      days. METHODS: Feces were collected on day 0 and day 14 from young rats (4 weeks
      old) and middle-aged rats (64 weeks old) fed with 17.7% chicken protein diets.
      The composition of the gut bacteria was analyzed by sequencing the V4-V5 region
      of the 16S ribosomal RNA gene. RESULTS: The results showed that the composition
      of the gut microbiota was significantly different between young and middle-aged
      rats on both day 0 and day 14. The percentage of Firmicutes decreased for middle
      aged rats (72.1% versus 58.1% for day 0 and day 14, respectively) but increased
      for young rats (41.5 versus 57.7% for day 0 and day 14, respectively). The
      percentage of Bacteroidetes increased to 31.2% (20.5% on day 0) for middle-aged
      rats and decreased to 29.6% (41.3% on day 0) for young rats. The relative
      abundance of the beneficial genus Lactobacillus increased in response to the
      intake of chicken protein in the young group, while it had the opposite effect in
      the middle-aged group. CONCLUSION: The results of our study demonstrated that
      17.7% chicken protein diet promoted the beneficial genus Lactobacillus in young
      rats, but the opposite effect were found in the middle-aged group. To evaluate
      the linkage between diet and host health, age effect should be considered in the
      future studies.

PMID- 27887576
TI  - Carotid arterial wall inflammation in peripheral artery disease is augmented by
      type 2 diabetes: a cross-sectional study.
AB  - BACKGROUND: Patients with peripheral artery disease (PAD) are at increased risk
      of secondary events, which is exaggerated in the presence of type 2 diabetes
      mellitus. Diabetes is associated with a systemic pro-inflammatory state. We
      therefore investigated the cumulative impact of PAD and type 2 diabetes on
      carotid arterial wall inflammation. As recent data suggest a detrimental role of
      exogenous insulin on cardiovascular disease, we also included a group of insulin
      users. RESULTS: 18F-fluorodeoxyglucose positron emission tomography with computed
      tomography (18F-FDG PET/CT) imaging showed increased carotid arterial wall
      inflammation, assessed as target-to-background ratio (TBR), in PAD patients
      without diabetes (PAD-only: n = 11, 1.97 +/- 0.57) compared with matched controls
      (n = 12, 1.49 +/- 0.57; p = 0.009), with a significant further TBR increase in
      PAD patients with type 2 diabetes (PAD-DM, n = 23, 2.90 +/- 1, p = 0.033 vs PAD
      only). TBR of insulin users (n = 12, 3.31 +/- 1.14) was higher compared with
      patients on oral medication only (n = 11, 2.44 +/- 0.76, p = 0.035), despite
      comparable PAD severity (Fontaine stages), BMI and CRP. Multivariate regression
      analysis showed that Hba1c and plasma insulin levels, but not dose of exogenous
      insulin, correlated with TBR. CONCLUSIONS: Concurrent diabetes significantly
      augments carotid arterial wall inflammation in PAD patients. A further increase
      in those requiring insulin was observed, which was associated with diabetes
      severity, rather than with the use of exogenous insulin itself.

PMID- 27887577
TI  - Impact of financial incentives on alcohol intervention delivery in primary care:
      a mixed-methods study.
AB  - BACKGROUND: Local and national financial incentives were introduced in England
      between 2008 and 2015 to encourage screening and brief alcohol intervention
      delivery in primary care. We used routine Read Code data and interviews with
      General Practitioners (GPs) to assess their impact. METHODS: A sequential
      explanatory mixed-methods study was conducted in 16 general practices
      representing 106,700 patients and 99 GPs across two areas in Northern England.
      Data were extracted on screening and brief alcohol intervention delivery for 2010
      11 and rates were calculated by practice incentive status. Semi-structured
      interviews with 14 GPs explored which factors influence intervention delivery and
      recording in routine consultations. RESULTS: Screening and brief alcohol
      intervention rates were higher in financially incentivised compared to non
      incentivised practices. However absolute rates were low across all practices.
      Rates of short screening test administration ranged from 0.05% (95% CI: 0.03
      0.08) in non-incentivised practices to 3.92% (95% CI: 3.70-4.14) in nationally
      incentivised practices. For the full AUDIT, rates were also highest in nationally
      incentivised practices (3.68%, 95% CI: 3.47-3.90) and lowest in non-incentivised
      practices (0.17%, 95% CI: 0.13-0.22). Delivery of alcohol interventions was
      highest in practices signed up to the national incentive scheme (9.23%, 95% CI:
      8.91-9.57) and lowest in non-incentivised practices (4.73%, 95% CI: 4.50-4.96).
      GP Interviews highlighted a range of influences on alcohol intervention delivery
      and subsequent recording including: the hierarchy of different financial
      incentive schemes; mixed belief in the efficacy of alcohol interventions; the
      difficulty of codifying complex conditions; and GPs' beliefs about patient
      centred practice. CONCLUSIONS: Financial incentives have had some success in
      encouraging screening and brief alcohol interventions in England, but levels of
      recorded activity remain low. To improve performance, future policies must
      prioritise alcohol prevention work within the quality and outcomes framework, and
      address the values, attitudes and beliefs that shape how GPs' provide care.

PMID- 27887578
TI  - Evaluation of an international educational programme for health care
      professionals on best practice in the management of a perinatal death: IMproving
      Perinatal mortality Review and Outcomes Via Education (IMPROVE).
AB  - BACKGROUND: Stillbirths and neonatal deaths are devastating events for both
      parents and clinicians and are global public health concerns. Careful clinical
      management after these deaths is required, including appropriate investigation
      and assessment to determine cause (s) to prevent future losses, and to improve
      bereavement care for families. An educational programme for health care
      professionals working in maternal and child health has been designed to address
      these needs according to the Perinatal Society of Australia and New Zealand
      Guideline for Perinatal Mortality: IMproving Perinatal mortality Review and
      Outcomes Via Education (IMPROVE). The programme has a major focus on stillbirth
      and is delivered as six interactive skills-based stations. We aimed to determine
      participants' pre- and post-programme knowledge of and confidence in the
      management of perinatal deaths, along with satisfaction with the programme. We
      also aimed to determine suitability for international use. METHODS: The IMPROVE
      programme was delivered to health professionals in maternity hospitals in all
      seven Australian states and territories and modified for use internationally with
      piloting in Vietnam, Fiji, and the Netherlands (with the assistance of the
      International Stillbirth Alliance, ISA). Modifications were made to programme
      materials in consultation with local teams and included translation for the
      Vietnam programme. Participants completed pre- and post-programme evaluation
      questionnaires on knowledge and confidence on six key components of perinatal
      death management as well as a satisfaction questionnaire. RESULTS: Over the
      period May 2012 to May 2015, 30 IMPROVE workshops were conducted, including 26
      with 758 participants in Australia and four with 136 participants
      internationally. Evaluations showed a significant improvement between pre- and
      post-programme knowledge and confidence in all six stations and overall, and a
      high degree of satisfaction in all settings. CONCLUSIONS: The IMPROVE programme
      has been well received in Australia and in three different international settings
      and is now being made available through ISA. Future research is required to
      determine whether the immediate improvements in knowledge are sustained with less
      causes of death being classified as unknown, changes in clinical practice and
      improvement in parents' experiences with care. The suitability for this programme
      in low-income countries also needs to be established.

PMID- 27887580
TI  - Factors associated with difficulty accessing health care for infants in Canada:
      mothers' reports from the cross-sectional Maternity Experiences Survey.
AB  - BACKGROUND: Approximately 13% of Canadian mothers report difficulty accessing
      health care for their infants, yet little is known about the factors associated
      with difficulty. Therefore, we examined factors associated with difficulty
      accessing non-routine health care for Canadian infants, from birth to 14 months
      of age, as reported by their mothers. METHODS: Data was drawn from the Maternity
      Experiences Survey (MES), a cross-sectional, nationally representative survey of
      mothers who gave birth between November 2005 and May 2006, aged 15 years or
      older, and lived with their infants at the time of survey administration. A
      multivariable logistic regression analysis was conducted to determine factors
      associated with reporting difficulty, with difficulty defined as a mother
      reporting it being somewhat or very difficult to access a health care provider.
      RESULTS: Analysis of 2832 mothers who reported needing to access a health care
      provider for their infant for a non-routine visit found that 13% reported
      difficulty accessing a provider. Factors associated with reporting difficulty
      were: residing in Quebec (aOR 1.89, 95% CI: 1.31-2.73), being an immigrant (aOR
      1.58, 95% CI: 1.10-2.27), mistimed pregnancy (aOR 1.44, 95% CI: 1.05-1.98), low
      level of social support (aOR 1.69, 95% CI: 1.05-2.73), good health (aOR 1.88, 95%
      CI: 1.43-2.47), postpartum depression symptoms (aOR 1.55, 95% CI: 1.02-2.37) and
      a self-reported 'too-short' postpartum hospital stay (aOR 1.69, 95% CI: 1.21
      2.35). Additionally, accessing care for an infant with a birth weight of 2500 g
      or more (aOR 2.43, 95% CI: 1.02-5.82), was associated with reporting difficulty.
      Household income, mothers' level of education, marital status, Aboriginal
      ethnicity, and size of community of residence were not associated with difficulty
      accessing care. CONCLUSIONS: Ease of health care access for Canadian infants is
      not equal, suggesting that efforts to improve access should be tailored to groups
      facing increased difficulties.

PMID- 27887579
TI  - Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin
      minimum inhibitory concentration in complicated urinary tract infections.
AB  - BACKGROUND: Fluoroquinolones are a guideline-recommended therapy for complicated
      urinary tract infections, including pyelonephritis. Elevated drug concentrations
      of fluoroquinolones in the urine and therapy with high-dose levofloxacin are
      believed to overcome resistance and effectively treat infections caused by
      resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov,
      NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an
      opportunity to test this hypothesis by examining the clinical and microbiological
      outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory
      concentration. METHODS: Patients were randomly assigned 1:1 to
      ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg
      intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided
      data on 370 patients with at least one isolate of Enterobacteriaceae at baseline
      who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5
      9 days after treatment) and late follow-up (21-42 days after treatment) visits in
      the microbiologically evaluable population (N = 327). RESULTS: Test-of-cure
      clinical cure rates above 90% were observed at minimum inhibitory concentrations
      <=4 MUg/mL. Microbiological eradication rates were consistently >90% at
      levofloxacin minimum inhibitory concentrations <=0.06 MUg/mL. Lack of eradication
      of causative pathogens at the test-of-cure visit increased the likelihood of
      relapse by the late follow-up visit. CONCLUSIONS: Results from this study do not
      support levofloxacin therapy for complicated urinary tract infections caused by
      organisms with levofloxacin minimum inhibitory concentrations >=4 MUg/mL. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT01345929 and NCT01345955.

PMID- 27887581
TI  - Design of a randomized controlled trial of Internet-based cognitive behavioral
      therapy for treatment-induced menopausal symptoms in breast cancer survivors.
AB  - BACKGROUND: Menopausal symptoms are common and may be particularly severe in
      younger women who undergo treatment-induced menopause. Medications to reduce
      menopausal symptoms are either contra-indicated or have bothersome side effects.
      Previous studies have demonstrated that face-to-face cognitive behavioral therapy
      (CBT) is effective in alleviating menopausal symptoms in women with breast
      cancer. However, compliance with face-to-face CBT programs can be problematic. A
      promising approach is to use the Internet to make this form of CBT more
      accessible and feasible for patients. This study is evaluating the efficacy and
      cost-effectiveness of an Internet-based CBT program, with or without therapist
      guidance, in alleviating or reducing the severity of menopausal symptoms.
      METHODS/DESIGN: In a multicenter, randomized controlled trial we are evaluating
      the efficacy of two Internet-based CBT programs in alleviating or reducing the
      impact of menopausal symptoms, and particularly hot flushes and night sweats, in
      breast cancer survivors who have experienced a treatment-induced menopause.
      Secondary outcomes include sexual functioning, sleep quality, hot flush
      frequency, psychological distress, health-related quality of life and cost
      effectiveness. We will recruit 248 women who will be randomized to either a
      therapist guided or a self-management version of the 6-week Internet-based CBT
      program, or to a usual care, waiting list control group. Self-administered
      questionnaires are completed at baseline (T0), and at 10 weeks (T1) and 24 weeks
      (T2) post-randomization. DISCUSSION: Internet-based CBT is a potentially useful
      treatment for reducing menopausal symptoms in breast cancer survivors. This study
      will provide evidence on the efficacy and cost-effectiveness of such an Internet
      based CBT program, with or without therapist support. If demonstrated to be
      efficacious and cost-effective, the availability of such structured supportive
      intervention programs will be a welcome addition to standard medical treatment
      offered to cancer patients with treatment-induced menopause. TRIAL REGISTRATION:
      The study is retrospectively registered at ClinicalTrials.gov on January 26th
      2016 ( NCT02672189 ).

PMID- 27887582
TI  - YPTB3816 of Yersinia pseudotuberculosis strain IP32953 is a virulence-related
      metallo-oligopeptidase.
AB  - BACKGROUND: Although bacterial peptidases are known to be produced by various
      microorganisms, including pathogenic bacteria, their role in bacterial physiology
      is not fully understood. In particular, oligopeptidases are thought to be mainly
      involved in degradation of short peptides e.g. leader peptides released during
      classical protein secretion pathways. The aim of this study was to investigate
      effects of inactivation of an oligopeptidase encoding gene opdA gene of Yersinia
      pseudotuberculosis on bacterial properties in vivo and in vitro, and to test
      dependence of the enzymatic activity of the respective purified enzyme on the
      presence of different divalent cations. RESULTS: In this study we found that
      oligopeptidase OpdA of Yersinia pseudotuberculosis is required for bacterial
      virulence, whilst knocking out the respective gene did not have any effect on
      bacterial viability or growth rate in vitro. In addition, we studied enzymatic
      properties of this enzyme after expression and purification from E. coli. Using
      an enzyme depleted of contaminant divalent cations and different types of
      fluorescently labelled substrates, we found strong dependence of its activity on
      the presence of particular cations. Unexpectedly, Zn2+ showed stimulatory
      activity only at low concentrations, but inhibited the enzyme at higher
      concentrations. In contrast, Co2+, Ca2+ and Mn2+ stimulated activity at all
      concentrations tested, whilst Mg2+ revealed no effect on the enzyme activity at
      all concentrations used. CONCLUSIONS: The results of this study provide valuable
      contribution to the investigation of bacterial peptidases in general, and that of
      metallo-oligopeptidases in particular. This is the first study demonstrating that
      opdA in Yersinia pseudotuberculsosis is required for pathogenicity. The data
      reported are important for better understanding of the role of OpdA-like enzymes
      in pathogenesis in bacterial infections. Characterisation of this protein may
      serve as a basis for the development of novel antibacterials based on specific
      inhibition of this peptidase activity.

PMID- 27887583
TI  - Impact of physical and mental health on life satisfaction in old age: a
      population based observational study.
AB  - BACKGROUND: It is widely assumed that poor health lowers life satisfaction when
      ageing. Yet, research suggests this relationship is not straightforward. This
      study investigated how older people evaluate their life when facing disease and
      disabilities. METHODS: The Leiden 85-plus Study, a prospectively followed cohort
      of a cohort of a middle-sized city in the Netherlands, all aged 85 years, that
      was age-representative of the general population, was used. Those with severe
      cognitive dysfunction were excluded (n = 501). Comorbidities, physical
      performance, cognitive function, functional status, residual lifespan, depressive
      symptoms and experienced loneliness were measured during home visits. Life
      satisfaction was self-reported with Cantril's ladder. All analyses were performed
      using regression analysis. RESULTS: Participants reported high life satisfaction
      (median 8 out of 10 points) despite having representative levels of disease and
      disability. Comorbidity, low cognitive function, and residual lifespan as markers
      of health were not associated with life satisfaction. Poor physical performance
      and low functional status were weakly but significantly associated with lower
      life satisfaction (p < 0.05 respectively p < 0.001), but significance was lost
      after adjustment for depressive symptoms and perceived loneliness. Depressive
      symptoms and perceived loneliness were strongly related to lower life
      satisfaction (both p < 0.001), even after adjustment for physical health
      characteristics. CONCLUSION: Poor physical health was hardly related to lower
      life satisfaction, whereas poor mental health was strongly related to lower life
      satisfaction. This indicates that mental health has a greater impact on life
      satisfaction at old age than physical health, and that physical health is less
      relevant for a satisfactory old age.

PMID- 27887584
TI  - Ratio of apoB/LDL: a potential clinical index for vascular cognitive impairment.
AB  - BACKGROUND: Vascular cognitive impairment (VCI), compared to vascular dementia
      (VD), has a broader definition and highlights the effect of vascular disease in
      dementia, and stroke seems play an important role in the development of VCI.
      However, not all patients with brain infarcts suffer from VCI; unique risk
      factors appear to cause such progression. This study aimed to find potential risk
      factors of vascular cognitive impairment among patients with brain infarcts.
      METHODS: Thirty-seven dementia patients and 74 brain infarction patients were
      included; all had infarcts in both basilar ganglia. The frequencies of risk
      factors, such as age, hypertension, and hyperlipidemia, were compared between the
      two groups. RESULTS: The incident rate of hyperlipidemia in the patients with
      dementia was 35.14%, which was significantly lower than that in the patients with
      infarction (59.46%, P = 0.015). In the dementia group, there was a positive
      correlation between the ratio of apoprotein B (apoB)/low density lipoprotein
      (LDL) and the Mini Mental State Examination (MMSE) score (R = 0.411, P = 0.011).
      CONCLUSION: Our study indicated that the ratio of apoB/LDL may be a potential
      clinical index for vascular cognitive impairment.

PMID- 27887585
TI  - Reduction in antibiotic prescribing for respiratory tract infections in Swedish
      primary care- a retrospective study of electronic patient records.
AB  - BACKGROUND: Swedish studies on antibiotic use in primary care have been based on
      one-week registrations of infections. In order to study adherence to guidelines,
      analyses based on large databases that provide information on diagnosis linked
      prescriptions, are needed. This study describes trends in management of
      infections in Swedish primary care particularly with regards to antibiotic
      prescribing and adherence to national guidelines. METHODS: A descriptive study of
      Sweden's largest database regarding diagnosis linked antibiotic prescription
      data, the Primary care Record of Infections in Sweden (PRIS), for the years 2008,
      2010 and 2013. RESULTS: Although the consultation rate for all infections
      remained around 30% each year, antibiotic prescribing rates decreased
      significantly over the years from 53.7% in 2008, to 45.5% in 2010, to 38.6% in
      2013 (p = .032). The antibiotic prescribing rate for respiratory tract infections
      (RTIs) decreased from 40.5% in 2008 to 24.9% in 2013 while those for urinary
      tract infections and skin and soft tissue infections were unchanged. For most RTI
      diagnoses there was a decrease in prescription rate from 2008 to 2013,
      particularly for the age group 0-6 years. Phenoxymethylpenicillin (PcV) was the
      antibiotic most often prescribed, followed by tetracycline. Tonsillitis and acute
      otitis media were the two RTI diagnoses with the highest number of prescriptions
      per 1000 patient years (PY). For these diagnoses an increase in adherence to
      national guidelines was seen, with regards to treatment frequency, choice of
      antibiotics and use of rapid antigen detection test. The frequency in antibiotic
      prescribing varied greatly between different Primary Healthcare Centres (PHCCs).
      CONCLUSION: Falling numbers of consultations and decreased antibiotic
      prescription rates for RTIs have reduced the antibiotic use in Swedish primary
      care substantially. Overprescribing of antibiotics could still be suspected due
      to large variability in prescribing frequency, especially for acute bronchitis
      and sinusitis. Continuous evaluation of diagnosis linked prescribing data and
      feedback to doctors is essential in order to achieve a more prudent antibiotic
      use.

PMID- 27887586
TI  - Hepatitis E virus seroepidemiology: a post-earthquake study among blood donors in
      Nepal.
AB  - BACKGROUND: As one of the causative agents of viral hepatitis, hepatitis E virus
      (HEV) has gained public health attention globally. HEV epidemics occur in
      developing countries, associated with faecal contamination of water and poor
      sanitation. In industrialised nations, HEV infections are associated with travel
      to countries endemic for HEV, however, autochthonous infections, mainly through
      zoonotic transmission, are increasingly being reported. HEV can also be
      transmitted by blood transfusion. Nepal has experienced a number of HEV
      outbreaks, and recent earthquakes resulted in predictions raising the risk of an
      HEV outbreak to very high. This study aimed to measure HEV exposure in Nepalese
      blood donors after large earthquakes. METHODS: Samples (n = 1,845) were collected
      from blood donors from Kathmandu, Chitwan, Bhaktapur and Kavre. Demographic
      details, including age and sex along with possible risk factors associated with
      HEV exposure were collected via a study-specific questionnaire. Samples were
      tested for HEV IgM, IgG and antigen. The proportion of donors positive for HEV
      IgM or IgG was calculated overall, and for each of the variables studied. Chi
      square and regression analyses were performed to identify factors associated with
      HEV exposure. RESULTS: Of the donors residing in earthquake affected regions
      (Kathmandu, Bhaktapur and Kavre), 3.2% (54/1,686; 95% CI 2.7-4.0%) were HEV IgM
      positive and two donors were positive for HEV antigen. Overall, 41.9% (773/1,845;
      95% CI 39.7-44.2%) of donors were HEV IgG positive, with regional variation
      observed. Higher HEV IgG and IgM prevalence was observed in donors who reported
      eating pork, likely an indicator of zoonotic transmission. Previous exposure to
      HEV in Nepalese blood donors is relatively high. CONCLUSION: Detection of recent
      markers of HEV infection in healthy donors suggests recent asymptomatic HEV
      infection and therefore transfusion-transmission in vulnerable patients is a risk
      in Nepal. Surprisingly, this study did not provide evidence of a large HEV
      outbreak following the devastating earthquakes in 2015.

PMID- 27887587
TI  - Experiences of support in working toward personal recovery goals: a
      collaborative, qualitative study.
AB  - BACKGROUND: Recovery can be understood as a subjective process guided by personal
      expectations, goals and hopes. The aim of the study was to explore how persons
      using a Community Mental Health Centre (CMHC) experienced that their expectations
      for treatment, and goals and hopes for recovery were supported by the health
      professionals during treatment. METHODS: Employing a hermeneutic-phenomenological
      approach, eight service users were interviewed about their expectations for
      treatment and their goals and hopes for recovery at the start of their contact
      with health professionals at a CMHC. Two years later, they were re-interviewed
      about their experiences of treatment and support from the health professionals in
      their work towards these goals and hopes. A collaborative approach was adopted. A
      co-researcher with lived experience took part in all stages of the study. Data
      were analysed by means of a data-driven stepwise approach in line with thematic
      analysis. RESULTS: Five themes reflecting how participants experienced support
      from health professionals at the CMHC in their work towards their recovery goals
      were elicited, as follows: developing an understanding of oneself and one's
      mental health problems; learning how to change feelings and behaviours; being
      'pushed' into social arenas; finding helpful medication; and counselling in
      family, practical and financial issues. The participants' expectations about
      counselling with regard to longer-term family, practical, and financial
      challenges were insufficiently met by the CMHC. In the experience of the service
      users, recovery occurred within the context of their everyday life with or
      without the support of their professional helpers. CONCLUSIONS: To facilitate
      recovery, health professionals should acknowledge the service user's personal
      goals and hopes and take a more comprehensive and longer-term approach to his or
      her needs and desires. Acknowledging and facilitating recovery goals by offering
      counselling with regard to family, practical and financial issues seems
      particularly important.

PMID- 27887588
TI  - Longitudinal reference ranges for maternal plasma laeverin, and its role as a
      potential biomarker of preeclampsia.
AB  - BACKGROUND: Laeverin is a placenta-specific membrane-bound aminopeptidase. In
      this study we wanted to: 1) serially measure plasma levels of laeverin in healthy
      women during the second half of pregnancy and postpartum, 2) determine whether
      laeverin is differently expressed at 22-24 weeks in women who later develop
      preeclampsia compared to controls, 3) compare laeverin protein expression in
      placenta and umbilical vein serum in healthy and preeclamptic pregnancies at
      birth. METHODS: Plasma was obtained serially, approximately every 4-weeks, from
      53 healthy women with uncomplicated pregnancies during 22+0 to 39+6 weeks of
      gestation, and at 22-24 weeks from 15 women who later developed preeclampsia.
      Enzyme-linked immunosorbent assay was used to measure laeverin protein
      concentration. Serum from healthy non-pregnant premenopausal women (n = 10),
      menopausal women (n = 10) and men (n = 11) were used as negative controls.
      Protein extracts from placental tissue were obtained after birth from healthy- (n
      = 11) and preeclamptic women (n = 13). Paired umbilical artery and vein serum
      samples from the neonates (n = 10) of healthy mothers were also analyzed.
      Multilevel modeling was used to determine the reference centiles. Differences
      between groups were analyzed using Student's t-test. RESULTS: Healthy pregnant
      women at term (37-40 weeks) had significantly higher plasma levels of laeverin
      (mean 4.95 +/- 0.32 ng/mL; p < 0.0001) compared to men (mean 0.18 +/- 0.31
      ng/mL), non-pregnant premenopausal women (mean 0.77 +/- 0.26 ng/mL) and
      postmenopausal women (mean 0.57 +/- 0.40 ng/mL). Maternal plasma laeverin levels
      decreased with advancing gestation, from 6.96 +/- 0.32 ng/mL at 22-24 weeks to
      4.95 +/- 0.32 ng/mL at term (p < 0.0001) in uncomplicated pregnancies. Half of
      the women who developed preeclampsia had plasma laeverin levels below the 5th
      percentile at 22-24 weeks gestation. However, laeverin levels were 1.6 fold
      higher in preeclamptic compared to healthy placentas (p = 0.0071). Umbilical
      venous samples of healthy neonates (n = 38) had higher (p = 0.001) mean levels of
      laeverin (16.63 +/- 0.73 ng/mL), compared to neonates of preeclamptic (n = 14)
      mothers (12.02 +/- 1.00 ng/mL). Postpartum plasma levels of laeverin decreased in
      healthy and preeclamptic women with a half-life of 3 and 5 days, respectively.
      CONCLUSIONS: Maternal plasma levels of laeverin decrease with advancing gestation
      during the second half of normal pregnancy and lower levels measured at 22-24
      weeks might be associated with the development of preeclampsia later in
      gestation.

PMID- 27887589
TI  - Guidelines for dementia or Parkinson's disease with depression or anxiety: a
      systematic review.
AB  - BACKGROUND: Depression and anxiety remain under-diagnosed and under-treated in
      those with neurologic diseases such as dementia or Parkinson's Disease (PD). Our
      objectives were to first, to provide a synthesis of high quality guidelines
      available for the identification and management of depression or anxiety in those
      with dementia or PD. Second, to identify areas for improvement for future
      guidelines. METHODS: We searched MEDLINE, PsycINFO, and EMBASE (2009 to July 24,
      2015), grey literature (83 sources; July 24-Sept 6, 2015), and bibliographies of
      included studies. Included studies were evaluated for quality by four independent
      reviewers the AGREE II tool. Guideline characteristics, statements and
      recommendations relevant to depression or anxiety for dementia and PD were then
      extracted. (PROSPERO CRD: 42016014584) RESULTS: 8121 citations were reviewed with
      31 full text articles included for assessment with the AGREE II tool. 17 were of
      sufficient quality for inclusion. Mean overall quality scores were between 4.25
      to 6.5. Domain scores were lowest in the areas of stakeholder involvement,
      applicability, and editorial independence. Recommendations for the screening and
      diagnosis of depression were found for PD and dementia. There was little evidence
      to guide diagnosis or management of anxiety. Non-pharmacologic therapies were
      recommended for dementia patients. Most advocated pharmacologic treatment for
      depression, for both PD and dementia, but did not specify an agent due to lack of
      evidence. CONCLUSIONS: The available recent high quality guidelines outline
      several recommendations for the management of comorbid depression or anxiety in
      PD or dementia. However there remain significant gaps in the evidence.

PMID- 27887590
TI  - Comparing the adverse clinical outcomes in patients with non-insulin treated type
      2 diabetes mellitus and patients without type 2 diabetes mellitus following
      percutaneous coronary intervention: a systematic review and meta-analysis.
AB  - BACKGROUND: Several studies showed Type 2 Diabetes Mellitus (T2DM) to be
      associated with worse adverse clinical outcomes compared to non-T2DM (NDM)
      following Percutaneous Coronary Intervention (PCI). In addition, patients with
      insulin-treated T2DM (ITDM) showed worse clinical outcomes compared to patients
      with non-insulin treated T2DM (NITDM). Since NITDM and NDM have seldom been
      systematically analyzed, this study aimed to compare the short and long term
      adverse clinical outcomes observed in patients with NITDM and patients without
      T2DM following PCI. METHODS: Medline/PubMed, EMBASE and the Cochrane library were
      searched for Randomized Controlled Trials (RCTs) and observational studies
      comparing patients with (including ITDM and NITDM) and without T2DM following
      PCI. Endpoints included adverse clinical outcomes reported during a short and a
      long term follow up period. Odd Ratios (OR) and 95% Confidence Intervals (CI) in
      accordance with either a fixed or a random effects model appropriately, were
      calculated and the pooled analyses were performed with RevMan 5.3. RESULTS:
      Twelve studies consisting of a total number of 52,451 patients (14,863 NITDM and
      37,588 NDM) were included. Patients with NITDM were found to have significantly
      higher short-term Major Adverse Cardiac Events (MACEs) and mortality with OR:
      1.63, 95% CI (1.17, 2.27); P = 0.004 and OR: 1.71, 95% CI (1.40, 2.10), P <
      0.00001 respectively and higher long-term MACEs and mortality with OR: 1.25, 95%
      CI (1.12, 1.40), P = 0.0001 and OR: 1.32, 95% CI (1.19, 1.47), P < 0.00001
      respectively compared to NDM following PCI. In addition, compared to NDM, long
      term Target Vessel Revascularization (TVR) and Target Lesion Revascularization
      (TLR) were significantly higher in the NITDM group with OR: 1.36, 95% CI (1.18,
      1.56), P < 0.0001 and OR: 1.32, 95% CI (1.10, 1.59), P = 0.003 respectively.
      However, even if an increased long-term stent thrombosis was observed in the
      NITDM group with OR: 1.13; 95% CI (0.91, 1.40), P = 0.28, the result was
      insignificant. CONCLUSION: Short and long term MACEs and mortality were
      significantly higher in patients with NITDM compared to patients without diabetes
      following PCI. Revascularization also significantly favored patients without
      T2DM. However, stent thrombosis was not significantly different.

PMID- 27887591
TI  - A prospective cohort study to assess seroprevalence, incidence, knowledge,
      attitudes and practices, willingness to pay for vaccine and related risk factors
      in dengue in a high incidence setting.
AB  - BACKGROUND: Dengue is one of the most important vector-borne diseases in the
      world, causing significant morbidity and economic impact. In Colombia, dengue is
      a major public health problem. Departments of La Guajira, Cesar and Magdalena are
      dengue endemic areas. The objective of this research is to determine the
      seroprevalence and the incidence of dengue virus infection in the participating
      municipalities from these Departments, and also establish the association between
      individual and housing factors and vector indices with seroprevalence and
      incidence. We will also assess knowledge, attitudes and practices, and
      willingness-to-pay for dengue vaccine. METHODS: A cohort study will be assembled
      with a clustered multistage sampling in 11 endemic municipalities. Approximately
      1000 homes will be visited to enroll people older than one year who living in
      these areas, who will be followed for 1 year. Dengue virus infections will be
      evaluated using IgG indirect ELISA and IgM and IgG capture ELISA. Additionally,
      vector indices will be measured, and adult mosquitoes will be captured with
      aspirators. Ovitraps will be used for continuous estimation of vector density.
      DISCUSSION: This research will generate necessary knowledge to design and
      implement strategies with a multidimensional approach that reduce dengue
      morbidity and mortality in La Guajira and other departments from Colombian
      Caribbean.

PMID- 27887592
TI  - Association of peripheral arterial disease with all-cause and cardiovascular
      mortality in hemodialysis patients: a meta-analysis.
AB  - BACKGROUND: Recent studies have shown an association between peripheral arterial
      disease (PAD) and increased risk of mortality in hemodialysis (HD) patients;
      however, the estimates vary widely and are inconsistent. It is necessary to
      elucidate the degree of mortality risk for PAD patients in HD population.
      METHODS: PubMed, EMBASE, Web of Science and Cochrane Library (from inception to
      September 4th, 2016) were systematically searched for cohort studies assessing
      the association between PAD and mortality in HD patients. We calculated the
      pooled risk ratios (RRs) with 95% confidence intervals (CI) of all-cause and
      cardiovascular (CV) mortality using random effects models. Subgroup analyses were
      conducted to explore the source of heterogeneity. RESULTS: The search identified
      2,973 potentially eligible records and 10 studies (n = 32,864) were included. Our
      meta-analysis revealed that PAD significantly increased the risk of all-cause
      mortality (RR 2.15, 95 % CI 1.67-2.77, n = 32,864) and CV mortality (RR 2.99, 95
      % CI 1.66-5.38, n = 31,794) in HD patients after multivariate adjustment.
      Subgroup analyses showed the study design and follow-up time might be two sources
      of heterogeneity. CONCLUSION: PAD may be a prognostic marker of all-cause and CV
      mortality in HD patients. More attention should be paid to diagnosis and
      management of PAD in HD patients.

PMID- 27887593
TI  - Expression of Barhl2 and its relationship with Pax6 expression in the forebrain
      of the mouse embryo.
AB  - BACKGROUND: The transcription factor Barhl2 is an antiproneural transcription
      factor with roles in neuronal differentiation. The functions of its homologue in
      Drosophila development are better understood than its functions in mammalian
      brain development. Existing evidence suggests that its expression in the
      embryonic forebrain of the mouse is regional and may complement that of another
      transcription factor that is important for forebrain development, Pax6. The aim
      of this study is to provide a more detailed description of the Barhl2 expression
      pattern in the embryonic forebrain than is currently available, to relate its
      expression domains to those of Pax6 and to examine the effects of Pax6 loss on
      Barhl2 expression. RESULTS: We found that Barhl2 is expressed in the developing
      diencephalon from the time of anterior neural tube closure. Its expression
      initially overlaps that of Pax6 in a central region of the alar diencephalon but
      over the following days their domains of expression become complementary in most
      forebrain regions. The exceptions are the thalamus and pretectum, where
      countergradients of Pax6 and Barhl2 expression are established by embryonic day
      12.5, before overall Pax6 levels in these regions decline greatly while Barhl2
      levels remain relatively high. We found that Barhl2 expression becomes
      upregulated in specifically the thalamus and pretectum in Pax6-null mice.
      CONCLUSIONS: The region-specific expression pattern of Barhl2 makes it likely to
      be an important player in the development of region-specific differences in
      embryonic mouse forebrain. Repression of its expression in the thalamus and
      pretectum by Pax6 may be crucial for allowing proneural factors to promote normal
      neuronal differentiation in this region.

PMID- 27887594
TI  - First trimester serum placental growth factor and hyperglycosylated human
      chorionic gonadotropin are associated with pre-eclampsia: a case control study.
AB  - BACKGROUND: To study whether maternal serum hyperglycosylated human chorionic
      gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when
      combined with placental growth factor (PlGF), pregnancy-associated plasma protein
      A (PAPP-A) and maternal risk factors. METHODS: Gestational-age-adjusted
      concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by
      time-resolved immunofluorometric assays at 8-13 weeks of gestation. The case
      control study included 98 women who developed pre-eclampsia, 25 who developed
      gestational hypertension, 41 normotensive women with small-for-gestational-age
      (SGA) infants and 177 controls. RESULTS: Of 98 women with pre-eclampsia, 24 women
      developed preterm pre-eclampsia (diagnosis < 37 weeks of gestation) and 13 of
      them had early-onset pre-eclampsia (diagnosis < 34 weeks of gestation). They had
      lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (%hCG-h) than
      controls. In receiver-operating characteristics (ROC) curve analysis, the area
      under the curve (AUC) for the combination of PlGF, PAPP-A, %hCG-h, nulliparity
      and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699
      0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750-0.988) for early-onset
      pre-eclampsia. Without %hCG-h the AUC values were 0.756 (95% CI 0.651-0.861) and
      0.810 (95% CI 0.682-0.938) respectively. For prediction of gestational
      hypertension, the AUC for %hCG-h was 0.708 (95% CI 0.608-0.808), but for other
      markers the AUC values were not significant. None of the AUC values were
      significant for the prediction of SGA infants in normotensive women. CONCLUSIONS:
      First trimester maternal serum %hCG-h tended to improve prediction of preterm and
      early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk
      factors.

PMID- 27887595
TI  - Antimicrobial stewardship of Chinese ministry of health reduces multidrug
      resistant organism isolates in critically ill patients: a pre-post study from a
      single center.
AB  - BACKGROUND: China's Ministry of Health (MOH) has established a policy about the
      antimicrobial stewardship. To date, the effects of this policy on multidrug
      resistant organism (MDRO) in critically ill patients are unknown. METHODS: A pre
      post study was conducted on intensive care unit (ICU) patients from June 2010 to
      May 2011 and from June 2012 to May 2013. Bacterial cultures were conducted at ICU
      admission and discharge. In June 2011, our hospital started to administer the
      antimicrobial stewardship program of Chinese MOH. We collected the data on
      antimicrobial consumption during the 3-year period in all hospital and individual
      department every month, and analyzed the correlation between the proportion of
      critically patients colonized or infected with MDRO and antimicrobial
      consumption. RESULTS: A total of 978 patients were involved in the present study.
      With the intervention, the monthly mean Defined Daily Dose (DDD) per 100 occupied
      bed-days throughout the hospital decreased from 96 +/- 7 to 65 +/- 6 (p < 0.001),
      and the proportion of patients colonized or infected with MDRO decreased from 36
      to 13% at the time of ICU admission and declined from 48 to 29% at the time of
      ICU discharge (both p < 0.001). There was a significant positive relationship
      between the proportion of all critically ill patients colonized or infected with
      MDRO at ICU admission and the DDD of the entire hospital (R2 = 0.7858, p <
      0.001). CONCLUSION: The antimicrobial stewardship program of Chinese MOH reduced
      the consumption of antibiotics. Moreover, the proportion of patients colonized or
      infected with MDRO decreased along with reduced consumption of antibiotics. TRIAL
      REGISTRATION: Retrospectively registered: NCT02128399; Date of registration: 22
      APR 2014; Detail information web link:
      https://clinicaltrials.gov/ct2/show/NCT02128399?term=NCT02128399&rank=1.

PMID- 27887596
TI  - Effectiveness, immunogenicity and safety of 23-valent pneumococcal polysaccharide
      vaccine revaccinations in the elderly: a systematic review.
AB  - BACKGROUND: In many industrialized countries routine vaccination with the 23
      valent pneumococcal polysaccharide vaccine (PPSV-23) is recommended to prevent
      pneumococcal disease in the elderly. However, vaccine-induced immunity wanes
      after a few years, and there are controversies around revaccination with PPSV-23.
      Here, we systematically assessed the effectiveness and safety of PPSV-23
      revaccination. METHOD: We conducted a systematic literature review in MEDLINE,
      EMBASE, and Cochrane Central Register of Controlled Trials from inception to June
      2015. We included all study types that compared effectiveness, immunogenicity
      and/or safety of PPSV-23 as a primary vs. a revaccination dose in persons aged 50
      years and older. With respect to immunogenicity, we calculated the ratio of
      geometric mean antibody concentrations and opsonophagocytic indexes at identical
      time-points after primary and revaccination. Additionally, we compared rates and
      severity of adverse events (AEs) after primary and revaccination. RESULTS: We
      included 14 observational studies. 10 studies had a prospective design and
      analysed data on (i) the same individuals after a first and a second dose of PPSV
      23 given 1 to 10 years later (n = 5) or (ii) two groups consisting of
      participants receiving PPSV-23 who were either vaccine-naive or had received a
      first PPSV-23 dose 3 to 13 years earlier (n = 5). Three studies used electronic
      data bases to compare AEs after primary vs. revaccination doses of PPSV-23 after
      1 to 10 years and one study had a cross-sectional design. Number of participants
      in the non-register-based and register-based studies ranged from 29 to 1414 and
      360 to 316,000, respectively. 11 out of 14 included studies were at high risk of
      bias, three studies had an unclear risk of bias. None of the studies reported
      data on clinical effectiveness. Immunogenicity studies revealed that during the
      first two months antibody levels tended to be lower after revaccination as
      compared to primary vaccination. Thereafter, no obvious differences in antibody
      levels were observed. Compared to primary vaccination, revaccination was
      associated with an increased risk of local and systemic AEs, which, however, were
      usually mild and self-limiting. The risk and severity of AEs appeared to decrease
      with longer intervals between primary and revaccination. CONCLUSION: Data
      comparing the effectiveness of primary vs. revaccination with PPSV-23 are still
      lacking, because there are no studies with clinical endpoints. Data from
      observational studies indicates that revaccination with PPSV-23 is likely to
      induce long-term antibody levels that are comparable to those after primary
      vaccination. Given the high disease burden and the waning of vaccine-induced
      immunity, revaccination with PPSV-23 could be considered in the elderly. The
      increased risk of local and systemic AEs can likely be mitigated when giving
      revaccination at least five years after the primary dose. Adequately powered
      randomized controlled trials using clinical endpoints are urgently needed.

PMID- 27887597
TI  - Technology-enhanced multi-domain at home continuum of care program with respect
      to usual care for people with cognitive impairment: the Ability
      TelerehABILITation study protocol for a randomized controlled trial.
AB  - BACKGROUND: According to the World Alzheimer Report (Prince, The Global Impact of
      Dementia: an Analysis of Prevalence, Incidence, Cost and Trends, 2015), 46.8
      million people worldwide are nowadays living with dementia. And this number is
      estimated to approximate 131.5 million by 2050, with an increasing burden on
      society and families. The lack of medical treatments able to stop or slow down
      the course of the disease has moved the focus of interest toward the
      nonpharmacological approach and psychosocial therapies for people with/at risk of
      dementia, as in the Mild Cognitive Impairment (MCI) condition. The purpose of the
      present study is to test an individualized home-based multidimensional program
      aimed at enhancing the continuum of care for MCI and outpatients with dementia in
      early stage using technology. METHODS: The proposed study is a single blind
      randomized controlled trial (RCT) involving 30 subjects with MCI and Alzheimer's
      disease (AD) randomly assigned to the intervention group (Ability group), who
      will receive the "Ability Program", or to the active control group (ACG), who
      will receive "Treatment As Usual" (TAU). The protocol provides for three steps of
      assessment: at the baseline (T_0), after treatment, (T_1) and at follow-up (T_2)
      with a multidimensional evaluation battery including cognitive functioning,
      behavioral, functional, and quality of life measures. The Ability Program lasts 6
      weeks, comprises tablet-delivered cognitive (5 days/week) and physical activities
      (7 days/week) combined with a set of devices for the measurement and monitoring
      from remote of vital and physical health parameters. The TAU equally lasts 6
      weeks and includes paper and pencil cognitive activities (5 days/week), with
      clinician's prescription to perform physical exercise every day and to monitor
      selected vital parameters. DISCUSSION: Results of this study will inform on the
      efficacy of a technology-enhanced home care service to preserve cognitive and
      motor levels of functioning in MCI and AD, in order to slow down their loss of
      autonomy in daily life. The expected outcome is to ensure the continuity of care
      from clinical practice to the patient's home, enabling also cost effectiveness
      and the empowerment of patient and caregiver in the care process, positively
      impacting on their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov ID:
      NCT02746484 (registration date: 12/apr/2016 - retrospectively registered).

PMID- 27887598
TI  - Comparison of the most common isolates of postoperative endophthalmitis in South
      Korea; Enterococcus species vs coagulase-negative staphylococci.
AB  - BACKGROUND: To compare the related factors or manifestations of the two most
      common isolates of post-operative endophthalmitis, which were Enterococcus spp.
      and coagulase-negative staphylococci (CNS) in South Korea. METHODS: Medical
      records were reviewed for cases of post-operative endophthalmitis caused by
      Enterococcus spp. and CNS at eight institutions between January 2004 and July
      2010. Various factors including age, sex, residence, systemic diseases, smoking
      and drinking history, and best corrected visual acuity, and length of time
      between causative intraocular surgery and symptom development were compared
      between the two groups. RESULTS: The total number of post-operative
      endophthalmitis cases was 128 and in 116 cases, microbiological culture tests
      from the aqueous humor or vitreous were performed. Among these cases, 67 (57.8%)
      were culture proven. Among these 67 cases, 19 (28.4%) were caused by Enterococcus
      spp., 14 (20.9%) were caused by Staphylococcus epidermidis endophthalmitis, and 5
      (7.5%) were caused by other CNS spp. Age, sex, causative procedure, past medical
      history, social history, and laterality were not different in the two groups.
      Mean initial and final visual acuity were significantly worse in the Enterococcus
      spp. endophthalmitis group than in the CNS group (p = 0.049, 0.042,
      respectively). Length of time between the causative procedure and symptom
      development was significantly shorter in cases of Enterococcus spp.
      endophthalmitis (p = 0.004). CONCLUSIONS: Enterococcus spp. induce more severe
      and rapid-onset postoperative endophthalmitis than CNS. Infectious
      endophthalmitis developed within 2 days after cataract operation could be caused
      by Enterococcus spp. and have chance to be poor prognosis in South Korea.

PMID- 27887599
TI  - How severe and prevalent are Ebola and Marburg viruses? A systematic review and
      meta-analysis of the case fatality rates and seroprevalence.
AB  - BACKGROUND: Ebola and Marburg virus diseases are said to occur at a low
      prevalence, but are very severe diseases with high lethalities. The fatality
      rates reported in different outbreaks ranged from 24-100%. In addition, sero
      surveys conducted have shown different seropositivity for both Ebola and Marburg
      viruses. We aimed to use a meta-analysis approach to estimate the case fatality
      and seroprevalence rates of these filoviruses, providing vital information for
      epidemic response and preparedness in countries affected by these diseases.
      METHODS: Published literature was retrieved through a search of databases.
      Articles were included if they reported number of deaths, cases, and
      seropositivity. We further cross-referenced with ministries of health, WHO and
      CDC databases. The effect size was proportion represented by case fatality rate
      (CFR) and seroprevalence. Analysis was done using the metaprop command in STATA.
      RESULTS: The weighted average CFR of Ebola virus disease was estimated to be
      65.0% [95% CI (54.0-76.0%), I2 = 97.98%] whereas that of Marburg virus disease
      was 53.8% (26.5-80.0%, I2 = 88.6%). The overall seroprevalence of Ebola virus was
      8.0% (5.0%-11.0%, I2 = 98.7%), whereas that for Marburg virus was 1.2% (0.5-2.0%,
      I2 = 94.8%). The most severe species of ebolavirus was Zaire ebolavirus while
      Bundibugyo Ebolavirus was the least severe. CONCLUSIONS: The pooled CFR and
      seroprevalence for Ebola and Marburg viruses were found to be lower than usually
      reported, with species differences despite high heterogeneity between studies.
      Countries with an improved health surveillance and epidemic response have lower
      CFR, thereby indicating need for improving early detection and epidemic response
      in filovirus outbreaks.

PMID- 27887600
TI  - Individual, household and community level factors associated with keeping
      tuberculosis status secret in Ghana.
AB  - BACKGROUND: In tuberculosis (TB) control, early disclosure is recommended for the
      purposes of treatment as well as a means of reducing or preventing person-to
      person transmission of the bacteria. However, disclosure maybe avoided as a means
      of escaping stigma, and possible discrimination. This study aimed at providing
      insights into factors associated with intentions of Ghanaians to keep positive TB
      diagnosis in their families' a secret. METHODS: The paper was based on data from
      the 2014 Ghana Demographic and Health Survey. Descriptive statistics of
      proportions with Chi-square test and binary logistic regression were used to
      identify individual, household and community level factors that predicted the
      outcome variable (keeping TB secret). RESULTS: Women were more inclined (33%)
      than men (25%) to keep TB in the family a secret. Views about keeping TB secret
      declined with age for both sexes. For women, higher education had a positive
      association with whether TB in the family would be kept a secret or not but the
      same was not observed for men. In a multivariable regression model, the strongest
      predictor of keeping TB secret was whether the respondent would keep HIV secret,
      and this was uniform among women (OR = 6.992, p < 0.001) and men (OR = 9.870, p <
      0.001). CONCLUSION: Unwillingness towards disclosing TB status in Ghana is
      associated with varied socioeconomic and demographic characteristics, which may
      be driven by fears of stigma and discrimination. Addressing TB-related stigma and
      discrimination can enhance positive attitudes towards TB disclosure. For an
      infectious disease such as TB, openness towards status disclosure is important
      for public health.

PMID- 27887601
TI  - Protocol for a prospective, randomized study on neurophysiological assessment of
      lower urinary tract function in a healthy cohort.
AB  - BACKGROUND: Lower urinary tract symptoms are highly prevalent and a large
      proportion of these symptoms are known to be associated with a dysfunction of the
      afferent pathways. Diagnostic tools for an objective and reproducible assessment
      of afferent nerve function of the lower urinary tract are missing. Previous
      studies showed first feasibility results of sensory evoked potential recordings
      following electrical stimulation of the lower urinary tract in healthy subjects
      and patients. Nevertheless, a refinement of the methodology is necessary.
      METHODS: This study is a prospective, randomized trial conducted at Balgrist
      University Hospital, Zurich, Switzerland. Ninety healthy subjects (forty females
      and fifty males) without lower urinary tract symptoms are planned to be included
      in the study. All subjects will undergo a screening visit (including standardized
      questionnaires, 3-day bladder diary, urinalysis, medical history taking, vital
      signs, physical examination, neuro-urological examination) followed by two
      measurement visits separated by an interval of 3 to 4 weeks. Electrical
      stimulations (0.5Hz-5Hz, bipolar, square wave, pulse width 1 ms) will be applied
      using a custom-made transurethral catheter at different locations of the lower
      urinary tract including bladder dome, trigone, proximal urethra, membranous
      urethra and distal urethra. Every subject will be randomly stimulated at one
      specific site of the lower urinary tract. Sensory evoked potentials (SEP) will be
      recorded using a 64-channel EEG cap. For an SEP segmental work-up we will place
      additional electrodes on the scalp (Cpz) and above the spine (C2 and L1). Visit
      two and three will be conducted identically for reliability assessment.
      DISCUSSION: The measurement of lower urinary tract SEPs elicited by electrical
      stimulation at different locations of the lower urinary tract has the potential
      to serve as a neurophysiological biomarker for lower urinary tract afferent nerve
      function in patients with lower urinary tract symptoms or disorders. For
      implementation of such a diagnostic tool into clinical practice, an optimized
      setup with efficient and reliable measurements and data acquisition is crucial.
      In addition, normative data from a larger cohort of healthy subjects would
      provide information on variability, potential confounding factors and cut-off
      values for investigations in patients with lower urinary tract
      dysfunction/symptoms. TRIAL REGISTRATION: Clinicaltrials.gov; Identifier:
      NCT02272309 .

PMID- 27887602
TI  - Combination of aspirin with essential fatty acids is superior to aspirin alone to
      prevent or ameliorate sepsis or ARDS.
AB  - It has been suggested that aspirin may be of benefit in treating sepsis and ARDS
      in view of its ability to block cyclo-oxygenase-1 (COX-1) and COX-2 activities;
      inhibit nuclear factor kappa B (NF-kappaB); enhance the production of endothelial
      nitric oxide (eNO) and lipoxin A4 (LXA4). Our previous studies revealed that
      plasma phospholipid content of arachidonic acid (AA) and eicosapentaenoic acid
      (EPA) is low in patients with sepsis. This implies that beneficial actions of
      aspirin in sepsis and ARDS is unlikely to be obtained in view of deficiency of AA
      and EPA, the precursors of LXA4 and resolvins respectively that are potent anti
      inflammatory compounds and enhancers of eNO generation. In view of this, I
      propose that a combination of aspirin and AA and EPA (and possibly,
      docosahexaenoic acid, DHA) is likely to be superior in the management of sepsis
      and ARDS compared to aspirin alone. This suggestion is supported by the recent
      observation that trauma patients with uncomplicated recoveries had higher
      resolvin pathway gene expression and lower gene expression ratios of leukotriene:
      resolvin pathways.

PMID- 27887603
TI  - Genetic elements associated with antimicrobial resistance among avian pathogenic
      Escherichia coli.
AB  - BACKGROUND: Avian-pathogenic Escherichia coli (APEC) are pathogenic strains of E.
      coli that are responsible for one of the most predominant bacterial disease
      affecting poultry worldwide called avian colibacillosis. This study describes the
      genetic determinants implicated in antimicrobial resistance among APEC isolated
      from different broiler farms in Egypt. METHODS: A total of 116 APEC were
      investigated by serotyping, antimicrobial resistance patterns to 10
      antimicrobials, and the genetic mechanisms underlying the antimicrobial-resistant
      phenotypes. RESULTS: Antibiogram results showed that the highest resistance was
      observed for ampicillin, tetracycline, nalidixic acid, and chloramphenicol. The
      detected carriage rate of integron was 29.3% (34/116). Further characterization
      of gene cassettes revealed the presence gene cassettes encoding resistance to
      trimethoprim (dfrA1, dfrA5, dfrA7, dfrA12), streptomycin/spectinomycin (aadA1,
      aadA2, aadA5, aadA23), and streptothricin (sat2). To our knowledge, this the
      first description of the presence of aadA23 in APEC isolates. Analysis of other
      antimicrobial resistance types not associated with integrons revealed the
      predominance of resistance genes encoding resistance to tetracycline (tetA and
      tetB), ampicillin (bla TEM), chloramphenicol (cat1), kanamycin (aphA1), and
      sulphonamide (sul1 and sul2). Among ciprofloxacin-resistant isolates, the S83L
      mutation was the most frequently substitution observed in the quinolone
      resistance-determining region of gyrA (56.3%). The bla TEM and bla CTX-M-1 genes
      were the most prevalent among APEC isolates producing extended-spectrum beta
      lactamase (ESbetaL). CONCLUSIONS: These findings provided important clues about
      the role of integron-mediated resistance genes together with other independent
      resistance genes and chromosomal mutations in shaping the epidemiology of
      antimicrobial resistance in E. coli isolates from poultry farms in Egypt.

PMID- 27887604
TI  - Variable ventilation improves pulmonary function and reduces lung damage without
      increasing bacterial translocation in a rat model of experimental pneumonia.
AB  - BACKGROUND: Variable ventilation has been shown to improve pulmonary function and
      reduce lung damage in different models of acute respiratory distress syndrome.
      Nevertheless, variable ventilation has not been tested during pneumonia.
      Theoretically, periodic increases in tidal volume (VT) and airway pressures might
      worsen the impairment of alveolar barrier function usually seen in pneumonia and
      could increase bacterial translocation into the bloodstream. We investigated the
      impact of variable ventilation on lung function and histologic damage, as well as
      markers of lung inflammation, epithelial and endothelial cell damage, and
      alveolar stress, and bacterial translocation in experimental pneumonia. METHODS:
      Thirty-two Wistar rats were randomly assigned to receive intratracheal of
      Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals
      were anesthetized and ventilated for 2 h with either conventional volume
      controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT = 6
      mL/kg, PEEP = 5cmH2O, and FiO2 = 0.4. During VV, tidal volume varied randomly
      with a coefficient of variation of 30% and a Gaussian distribution. Additional
      animals assigned to receive either PA or SAL (n = 8/group) were not ventilated
      (NV) to serve as controls. RESULTS: In both SAL and PA, VV improved oxygenation
      and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6
      expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3
      [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV
      (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced
      perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum
      neutrophils (2.0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis
      (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage
      scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU)
      counts were comparable (7 [0-28] vs. 6 [0-26], p = 0.77). Compared to NV, VCV,
      but not VV, increased expression amphiregulin, IL-6, and cytokine-induced
      neutrophil chemoattractant (CINC)-1 (2.1 [1.6-2.5] vs. 0.9 [0.7-1.2], p = 0.025;
      12.3 [7.9-22.0] vs. 0.8 [0.6-1.9], p = 0.006; and 4.4 [2.9-5.6] vs. 0.9 [0.8
      1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV
      compared to NV animals (0.5 [0.3-0.8] vs. 1.3 [1.0-1.5], p = 0.01). CONCLUSION:
      In this rat model of pneumonia, VV improved pulmonary function and reduced lung
      damage as compared to VCV, without increasing bacterial translocation.

PMID- 27887605
TI  - A randomised, open-labelstudy of insulin glargine or neutral protamine Hagedorn
      insulin in Chinese paediatric patients with type 1 diabetes mellitus.
AB  - BACKGROUND: We aimed to describe the safety and efficacy of insulin glargine in
      Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral
      protamine Hagedorn (NPH) insulin was the reference therapy. METHODS: This open
      label, randomised, Phase III study was conducted at 10 sites in China. Children
      aged >=6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH
      insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin
      aspart was given as bolus insulin. The primary endpoint was absolute change in
      glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints
      included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and
      safety. The study was registered at clinicaltrials.gov (NCT01223131). RESULTS: In
      total,196 patients were screened, and 162 were randomised (107 and 55 patients
      were randomised to insulin glargine and NPH insulin, respectively). The mean +/-
      SD of absolute change in HbA1c was-0.25 +/- 1.68% (-2.69 +/- 18.32 mmol/mol) in
      the insulin glargine group and -0.54 +/- 1.67% (-5.55 +/- 20.32 mmol/mol) in the
      NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine
      and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments
      were generally well tolerated. A numerically lower rate of symptomatic
      hypoglycaemia per patient year was observed for insulin glargine versus NPH
      insulin (24.3 +/- 45.8 versus32.3 +/- 43.2); severe hypoglycaemia was rare (<2%).
      CONCLUSIONS: Initiation of insulin glargine can aid Chinese paediatric patients
      with T1DM to safely reduce their HbA1c levels.

PMID- 27887606
TI  - Cancer somatic mutations cluster in a subset of regulatory sites predicted from
      the ENCODE data.
AB  - BACKGROUND: Transcriptional regulation of gene expression is essential for
      cellular differentiation and function, and defects in the process are associated
      with cancer. The ENCODE project has mapped potential regulatory sites across the
      complete genome in many cell types, and these regions have been shown to harbour
      many of the somatic mutations that occur in cancer cells, suggesting that their
      effects may drive cancer initiation and development. The ENCODE data suggests a
      very large number of regulatory sites, and methods are needed to identify those
      that are most relevant and to connect them to the genes that they control.
      METHODS: Predictive models of gene expression were developed by integrating the
      ENCODE data for regulation, including transcription factor binding and DNase1
      hypersensitivity, with RNA-seq data for gene expression. A penalized regression
      method was used to identify the most predictive potential regulatory sites for
      each transcript. Known cancer somatic mutations from the COSMIC database were
      mapped to potential regulatory sites, and we examined differences in the mapping
      frequencies associated with sites chosen in regulatory models and other
      (rejected) sites. The effects of potential confounders, for example replication
      timing, were considered. RESULTS: Cancer somatic mutations preferentially occupy
      those regulatory regions chosen in our models as most predictive of gene
      expression. CONCLUSION: Our methods have identified a significantly reduced set
      of regulatory sites that are enriched in cancer somatic mutations and are more
      predictive of gene expression. This has significance for the mechanistic
      interpretation of cancer mutations, and the understanding of genetic regulation.

PMID- 27887607
TI  - Erratum to: The effectiveness of non-pyrethroid insecticide-treated durable wall
      lining to control malaria in rural Tanzania: study protocol for a two-armed
      cluster randomized trial.

PMID- 27887608
TI  - Role of NCAN rs2228603 polymorphism in the incidence of nonalcoholic fatty liver
      disease: a case-control study.
AB  - BACKGROUND: Recently genome-wide association studies identified that NCAN
      rs2228603 polymorphism was associated with non-alcoholic fatty liver disease
      (NAFLD) mainly in subjects of European ancestry. While no research have been
      conducted to demonstrate the relationship between NCAN rs2228603 and NAFLD in
      Chinese Han adults. The aim of this study was to investigate whether NCAN
      rs2228603 is associated with NAFLD in Chinese population. METHODS: Gene NCAN
      rs2228603 was genotyped in 182 patients with NAFLD and 195 healthy controls. The
      expression of NCAN was tested according to polymerase chain reaction analysis
      (PCR) and serum lipids were performed by biology techniques. RESULTS: No
      significant difference was found in genotype and allele frequencies of NCAN
      rs2228603 between the NAFLD group and the controls (P > 0.05). Subjects with the
      NCAN rs2228603 CT genotype showed a higher level of alkaline phosphatase (AKP) (P
      = 0.017) and a higher high-density lipoprotein (HDL) (P < 0.05). CONCLUSIONS: Our
      study for the first time identified that the gene NCAN rs2228603 is not a risk
      factor for the incidence of NAFLD in Chinese population. Also we found the dual
      and opposite role of T variant in protecting liver with a higher level of HDL and
      conferring risk for liver damage with a higher level of AKP. TRIAL REGISTRATION:
      Chinese Clinical Trial Register.gov Identifier: ChiCTR-ROC-15006447 .

PMID- 27887609
TI  - Cytotoxic effects of ergone, a compound isolated from Fulviformes fastuosus.
AB  - BACKGROUND: Mushrooms inspired the cuisines of many cultures and conventional
      medicaments for cancer. However, a substantial number of mushroom species are yet
      unexplored, possessing an unknown chemical, biological and pharmacological
      profiles. Fulviformes fastuosus is a terrestrial mushroom, which is commonly
      found in Sri Lankan woodlands. The current study was aimed at isolation and
      characterization of a potent cytotoxic compound from F. fastuosus and
      investigating the apoptotic effect induced by the active principle against cancer
      and normal cell lines. METHODS: Bioactivity guided isolation of active principles
      from the methanol extract of F. fastuosus was performed by a rapid extraction and
      isolation method using different chromatographic techniques. Potential cytotoxic
      compound was identified using one and two dimensional nuclear magnetic resonance
      spectroscopy and mass spectrometry. Isolated compound was screened for in vitro
      cytotoxicity against Hepatocellular carcinoma (HepG-2), Muscle rhabdomyosarcoma
      (RD) and Rat Wistar liver normal (CC-1) cell lines using 3 4, 5-(dimethylthiazol
      2-yl) 2-5-diphenyl tetrazolium bromide (MTT) cell viability assay. Apoptotic
      features of cells were observed via microscopic examination and ethidium
      bromide/acridine orange fluorescent staining. RESULTS: The interpretation of
      spectral data resulted in the identification of the chemical structure as ergosta
      4,6,8 (14),22-tetraen-3-one (ergone). Ergone exhibited promising cytotoxic
      properties against RD cells with less cytotoxicity effect on CC-1 cells. In
      addition, ergone also possesses a strong cytotoxic effect against HepG-2 cells
      showing low toxic level for CC-1 cells. Apoptotic features of treated cells were
      detected via morphological characterization and ethidium bromide/acridine orange
      staining. CONCLUSION: The present study elaborates the isolation of a potent
      cytotoxic compound; ergone, from F. fastuosus via a rapid and efficient isolation
      method. Importantly, ergone has exhibited greater cytotoxic activity against RD
      cells with high selectivity index compared to cytotoxicity against HepG-2 cells.
      Ergone can be used in the development of therapeutic strategies for curbing
      rhabdomyosarcoma.

PMID- 27887610
TI  - Integral strategy to supportive care in breast cancer survivors through
      occupational therapy and a m-health system: design of a randomized clinical
      trial.
AB  - BACKGROUND: Technological support using e-health mobile applications (m-health)
      is a promising strategy to improve the adherence to healthy lifestyles in breast
      cancer survivors (excess in energy intake or low physical activity are
      determinants of the risk of recurrence, second cancers and cancer mortality).
      Moreover, cancer rehabilitation programs supervised by health professionals are
      needed due to the inherent characteristics of these breast cancer patients. Our
      main objective is to compare the clinical efficacy of a m-health lifestyle
      intervention system alone versus an integral strategy to improve Quality of Life
      in breast cancer survivors. METHODS: This therapeutic superiority study will use
      a two-arm, assessor blinded parallel RCT design. Women will be eligible if: they
      are diagnosed of stage I, II or III-A breast cancer; are between 25 and 75 years
      old; have a Body Mass Index > 25 kg/m2; they have basic ability to use mobile
      apps; they had completed adjuvant therapy except for hormone therapy; and they
      have some functional shoulder limitations. Participants will be randomized to one
      of the following groups: integral group will use a mobile application (BENECA
      APP) and will receive a face-to-face rehabilitation (8-weeks); m-health group
      will use the BENECA app for 2-months and will received usual care information.
      Study endpoints will be assessed after 8 weeks and 6 months. The primary outcome
      will be Quality of Life measured by The European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire Core and breast module. The
      secondary outcomes: body composition; upper-body functionality (handgrip,
      Disability of the Arm, Shoulder and Hand questionnaire, goniometry); cognitive
      function (Wechsler Adult Intelligence Scale, Trail Making Test); anxiety and
      depression (Hospital Anxiety and Depression Scale); physical fitness (Short
      version of the Minnesota Leisure Time Physical Activity Questionnaire, Self
      Efficacy Scale for Physical Activity); accelerometry and lymphedema. DISCUSSION:
      This study has been designed to seek to address the new needs for support and
      treatment of breast cancer survivors, reflecting the emerging need to merge new
      low cost treatment options with much-needed involvement of health professionals
      in this type of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT02817724 (date of registration: 22/06/2016).

PMID- 27887611
TI  - The performance of interferon-gamma release assay in nontuberculous mycobacterial
      diseases: a retrospective study in China.
AB  - BACKGROUND: The interferon-gamma release assay (IGRA) is more specific than the
      tuberculin skin test to discriminate between tuberculosis (TB) and nontuberculous
      mycobacterial (NTM) diseases. Here we performed a retrospective study to evaluate
      the performance of the T-SPOT.TB in patients with NTM diseases. METHODS: Between
      March, 2013 and Nov, 2015, a total of 58 patients with NTM diseases had a T
      SPOT.TB performed were enrolled, 30 patients had definite NTM diseases, 28 had
      probable diseases. Their clinicopathological characteristics were reviewed and
      analyzed. Cultures for mycobacteria were performed. The indirect proportion
      method with Lowenstein-Jensen (L-J) medium was used for first-line drug
      susceptibility test. T-SPOT.TB assay was performed according to the
      manufacturer's instructions. Data were expressed as mean +/- standard deviation
      (continuous variables) and as numbers and percentages (categorical variables).
      The chi 2 test was used for comparisons between proportions. RESULTS: The average
      age was 51.8 +/- 16.1 years (range 10 to 77 years), 58.6% (34/58) were male.
      16.4% (9/55) were TB-PCR positive. 34 (58.6%) isolates were Mycobacterium
      intracellulare, ten (17.2%) were Mycobacterium chelonae and seven (12.1%) were
      Mycobacterium fortuitum. Fifty-two (89.7%) patients were NTM lung disease, five
      (8.6%) were pleural disease, and one (1.7%) lymphadenitis. The total positivity
      of T-SPOT.TB was 53.4% (31/58) among the whole group (probable and definite). For
      probable cases, the T-SPOT.TB assay was positive in 53.5% (15/28); for definite
      cases, 16 (53.3%) of 30 definite cases were positive. There was no statistical
      difference in the positivity rate between them (P < 0.01). CONCLUSIONS: In the
      study, we showed that a significant portion of NTM diseases were T-SPOT.TB
      positive in China. Although T-SPOT.TB is useful diagnostic method for
      differentiating TB from NTM diseases, in China, the IGRA assay show limited value
      in the discrimination. In addition, further research is needed to investigate the
      association between TB infection and treatment for NTM patients.

PMID- 27887612
TI  - Phenotyping the Snark: hazards of 3D.

PMID- 27887613
TI  - Enhancing evidence use in public health nutrition policymaking: theoretical
      insights from a New Zealand case study.
AB  - BACKGROUND: Enhancing the use of evidence in policymaking is critical to
      addressing the global burden of nutrition-related disease. Whilst the public
      health nutrition community has embraced evidence-informed policymaking, their
      approach of defining relevant evidence and evaluating policy has not brought
      about major shifts in policymaking. This article uses a public health nutrition
      case study to refine a novel theory-informed framework for enhancing the use of
      evidence in government public health nutrition policymaking. Our aim is to
      contribute insights from evidence-informed policy to the emerging paradigm in
      public health nutrition policymaking. METHODS: An enquiry framework informed by
      three groups of theories underpinning evidence-informed policy was used to
      explore the role of socially mediated processes on the use of evidence. A public
      health nutrition case study on food marketing to New Zealand children was
      conducted to refine the framework. Interview data collected from 54 individuals
      representing four key policy stakeholder groups, policymakers, academics, and
      food industry and non-government organisations were analysed using deductive and
      inductive thematic analysis. To enhance theoretical robustness, an alternative
      hypothesis of political explanations for evidence use was explored alongside the
      enquiry framework. RESULTS: We found the prevailing political climate influenced
      the impact of advocacy for evidence inclusive processes at the meta-policy and
      policymaking process levels and in policy community relationships. Low levels of
      awareness of the impact of these processes on evidence use and uncoordinated
      advocacy resulted in the perpetuation of ad hoc policymaking. These findings
      informed refinements to the enquiry framework. CONCLUSION: Our study highlights
      the role advocates can play in shifting government public health nutrition
      policymaking systems towards enhanced use of evidence. Our Advocacy for Evidence
      Use framework argues for a three-channel approach to advocacy for using evidence
      in the public interest. The framework provides a means for building a
      constituency for evidence use in public health nutrition and adds understanding
      about advocacy to the field of evidence-informed policy. Future research should
      examine the impact of coordinated advocacy on public health nutrition
      policymaking systems.

PMID- 27887614
TI  - Insight into k13-propeller gene polymorphism and ex vivo DHA-response profiles
      from Cameroonian isolates.
AB  - BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin
      derivatives in Southeast Asia is a major source of concern and the emergence of
      resistance in Africa would have dramatic consequences, by increasing malaria
      mortality and morbidity. It is therefore urgent to implement regular monitoring
      in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools.
      The prevalence of k13-propeller mutations and the phenotypic profiles are poorly
      known in sub-Saharan Africa. Here, the k13-propeller polymorphism was compared to
      both ex vivo susceptibility to DHA and early parasitological and clinical
      responses to artemisinin combination therapy (ACT). METHODS: Plasmodium
      falciparum isolates were collected in 2015 in Yaounde (Cameroon) from patients
      treated with dihydroartemisinin-piperaquine combination. Samples were analysed
      for their susceptibility to artemisinin using the k13-propeller sequencing, the
      ex vivo ring-stage survival assay, the in vivo parasite positive rate and the
      clinical statute at day 2. RESULTS: None of the collected isolates revealed the
      presence of resistance mutations in the k13-propeller sequence. The median ring
      stage survival rate for all the 64 interpretable isolates after a 6-hour pulse of
      700 nM dihydroartemisinin was low, 0.49% (IQR: 0-1.3). Total parasite clearance
      was observed for 87.5% of patients and the remaining parasitaemic isolates
      (12.5%) showed a high reduction of parasite load, ranging from 97.5 to 99.9%.
      Clinical symptoms disappeared in 92.8% of cases. CONCLUSION: This study
      demonstrated the absence of k13-resistant genotypes in P. falciparum isolates
      from Cameroon. Only synonymous mutations were found with a low prevalence (4.3%).
      A good association between k13 genotypes and the ex vivo ring-stage survival
      assay or parasitological and clinical data was obtained. These results give a
      baseline for the long-term monitoring of artemisinin derivative efficacy in
      Africa.

PMID- 27887615
TI  - Developing a set of strong intronic promoters for robust metabolic engineering in
      oleaginous Rhodotorula (Rhodosporidium) yeast species.
AB  - BACKGROUND: Red yeast species in the Rhodotorula/Rhodosporidium genus are
      outstanding producers of triacylglyceride and cell biomass. Metabolic engineering
      is expected to further enhance the productivity and versatility of these hosts
      for the production of biobased chemicals and fuels. Promoters with strong
      activity during oil-accumulation stage are critical tools for metabolic
      engineering of these oleaginous yeasts. RESULTS: The upstream DNA sequences of 6
      genes involved in lipid biosynthesis or accumulation in Rhodotorula toruloides
      were studied by luciferase reporter assay. The promoter of perilipin/lipid
      droplet protein 1 gene (LDP1) displayed much stronger activity (4-11 folds) than
      that of glyceraldehyde-3-phosphate dehydrogenase gene (GPD1), one of the
      strongest promoters known in yeasts. Depending on the stage of cultivation,
      promoter of acetyl-CoA carboxylase gene (ACC1) and fatty acid synthase beta
      subunit gene (FAS1) exhibited intermediate strength, displaying 50-160 and 20-90%
      levels of GPD1 promoter, respectively. Interestingly, introns significantly
      modulated promoter strength at high frequency. The incorporation of intron 1 and
      2 of LDP1 (LDP1in promoter) enhanced its promoter activity by 1.6-3.0 folds.
      Similarly, the strength of ACC1 promoter was enhanced by 1.5-3.2 folds if
      containing intron 1. The intron 1 sequences of ACL1 and FAS1 also played
      significant regulatory roles. When driven by the intronic promoters of ACC1 and
      LDP1 (ACC1in and LDP1in promoter, respectively), the reporter gene expression
      were up-regulated by nitrogen starvation, independent of de novo oil biosynthesis
      and accumulation. As a proof of principle, overexpression of the endogenous acyl
      CoA-dependent diacylglycerol acyltransferase 1 gene (DGA1) by LDP1in promoter was
      significantly more efficient than GPD1 promoter in enhancing lipid accumulation.
      CONCLUSION: Intronic sequences play an important role in regulating gene
      expression in R. toruloides. Three intronic promoters, LDP1in, ACC1in and FAS1in,
      are excellent promoters for metabolic engineering in the oleaginous and
      carotenogenic yeast, R. toruloides.

PMID- 27887616
TI  - Weak outcome predictors of multimodal rehabilitation at one-year follow-up in
      patients with chronic pain-a practice based evidence study from two SQRP centres.
AB  - BACKGROUND: For patients with chronic pain, the heterogeneity of clinical
      presentations makes it difficult to identify patients who would benefit from
      multimodal rehabilitation programs (MMRP). Yet, there is limited knowledge
      regarding the predictors of MMRP's outcomes. This study identifies predictors of
      outcome of MMRPs at a 12-month follow-up (FU-12) based on data from the Swedish
      Quality Registry for Pain Rehabilitation (SQRP). METHODS: Patients with chronic
      pain from two clinical departments in Sweden completed the SQRP questionnaires
      background, pain characteristics, psychological symptoms, function,
      activity/participation, health and quality of life-on three occasions: 1) during
      their first visit; 2) immediately after the completion of their MMRP; and 3) 12
      months after completing the MMRP (n = 227). During the FU-12, the patients also
      retrospectively reported their global impressions of any changes in their
      perception of pain and their ability to handle their life situation in general.
      RESULTS: Significant improvements were found for pain, psychological symptoms,
      activity/participation, health, and quality of life aspects with low/medium
      strong effects. A general pattern was observed from the analyses of the changes
      from baseline to FU-12; the largest improvements in outcomes were significantly
      associated with poor situations according to their respective baseline scores.
      Although significant regressors of the investigated outcomes were found, the
      significant predictors were weak and explained a minor part of the variation in
      outcomes (15-25%). At the FU-12, 53.6% of the patients reported that their pain
      had decreased and 80.1% reported that their life situation in general had
      improved. These improvements were associated with high education, low pain
      intensity, high health level, and work importance (only pain perception). The
      explained variations were low (9-11%). CONCLUSIONS: Representing patients in real
      world clinical settings, this study confirmed systematic reviews that outcomes of
      MMRP are associated with broad positive effects. A mix of background and baseline
      variables influenced the outcomes investigated, but the explained variations in
      outcomes were low. There is still a need to develop standardized and relatively
      simple outcomes that can be used to evaluate MMRP in trials, in clinical
      evaluations at group level, and for individual patients.

PMID- 27887617
TI  - Increased expression of TROP2 in airway basal cells potentially contributes to
      airway remodeling in chronic obstructive pulmonary disease.
AB  - BACKGROUND: The airway epithelium of chronic obstructive pulmonary disease (COPD)
      patients undergoes aberrant repair and remodeling after repetitive injury
      following exposure to environmental factors. Abnormal airway regeneration
      observed in COPD is thought to originate in the stem/progenitor cells of the
      airway epithelium, the basal cells (BCs). However, the molecular mechanisms
      underlying these changes remain unknown. Here, trophoblast cell surface antigen 2
      (TROP2), a protein implicated in the regulation of stem cell activity, was
      examined in lung tissue samples from COPD patients. METHODS: The expression of
      TROP2 and hyperplasia index Ki67 was assessed in lung epithelium specimens from
      non-smokers (n = 24), smokers (n = 24) and smokers with COPD (n = 24). Primary
      airway BCs were isolated by bronchoscopy from healthy individuals and COPD
      patients and subsequently transfected with pcDNA3.1-TROP2 or siRNA sequence in
      vitro. The functional consequences of TROP2 overexpression in BCs were explored.
      RESULTS: Immunohistochemistry and immunofluorescence revealed increased TROP2
      expression in airway BCs in smokers with COPD compared to nonsmokers and smokers
      without COPD, and staining was highly localized to hyperplastic regions
      containing Ki67 positive cells. TROP2 expression was also inversely correlated
      with airflow limitation in patients with COPD (r = -0.53, P < 0.01). pcDNA3.1
      TROP2-BCs in vitro exhibited improved proliferation with activation of ERK1/2
      phosphorylation signaling pathway. In parallel, changes in vimentin and E
      cadherin in pcDNA3.1-TROP2-BCs were consistent with an epithelial-mesenchymal
      transition (EMT)-like change, and secretion of inflammatory factors IL-1beta, IL
      8 and IL-6 was increased. Moreover, down-regulation of TROP2 by siRNA
      significantly attenuated the proliferation of BCs derived from COPD patients. EMT
      like features and cytokine levels of COPD basal cells were also weakened
      following the down-regulation of TROP2. CONCLUSION: The results indicate that
      TROP2 may play a crucial role in COPD by affecting BC function and thus airway
      remodeling through increased BC hyperplasia, EMT-like change, and introduction of
      inflammatory molecules into the microenvironment.

PMID- 27887618
TI  - Portable air cleaners should be at the forefront of the public health response to
      landscape fire smoke.
AB  - Landscape fires can produce large quantities of smoke that degrade air quality in
      both remote and urban communities. Smoke from these fires is a complex mixture of
      fine particulate matter and gases, exposure to which is associated with increased
      respiratory and cardiovascular morbidity and mortality. The public health
      response to short-lived smoke events typically advises people to remain indoors
      with windows and doors closed, but does not emphasize the use of portable air
      cleaners (PAC) to create private or public clean air shelters. High efficiency
      particulate air filters and electrostatic precipitators can lower indoor
      concentrations of fine particulate matter and improve respiratory and
      cardiovascular outcomes. We argue that PACs should be at the forefront of the
      public health response to landscape fire smoke events.

PMID- 27887619
TI  - The prognostic value of measurement of high-sensitive cardiac troponin T for
      mortality in a cohort of stable chronic obstructive pulmonary disease patients.
AB  - BACKGROUND: Cardiovascular disease (CVD) is a common comorbidity in chronic
      obstructive pulmonary disease (COPD). Cardiac troponin (cTn) elevation,
      indicating myocardial injury, is frequent during acute COPD exacerbations and
      associated with increased mortality. The prognostic value of circulating cTnT
      among COPD patients in the stable state of the disease is still unknown. The
      purpose of the present study was to assess the association between circulating
      cTnT measured by a high sensitive assay (hs-cTnT) and all-cause mortality among
      patients with stable COPD without overt CVD. METHODS: In a prospective cohort
      study we included 275 patients from the Akershus University Hospital's outpatient
      clinic and from Glittre, a pulmonary rehabilitation clinic. COPD-severity and
      cardiovascular risk factors were assessed, and time to all-cause death was
      recorded during a mean follow-up time of 2.8 years. RESULTS: One hundred-eighty
      patients (65%) had hs-cTnT concentrations >= the level of detection (5.0 ng/L)
      and 66 patients (24%) had hs-cTnT above the normal range (>=14.0 ng/L). In total,
      47 patients (17%) died. hs-cTnT concentrations in the ranges <5.0, 5.0-13.9 and
      >=14 ng/L were associated with crude mortality rates of 2.8, 4.4 and 11.0 per 100
      patient-years, respectively. In adjusted analyses the hazard ratios (95%
      confidence intervals) for death were 1.7 (0.8-3.9) and 2.9 (1.2-7.2) among
      patients with hs-cTnT concentrations 5.0-13.9 and >=14 ng/L, respectively,
      compared to patients with hs-cTnT <5.0 ng/L. CONCLUSIONS: hs-cTnT elevation is
      frequently present in patients with stable COPD without overt CVD, and associated
      with increased mortality, independently of COPD-severity and other cardiovascular
      risk factors.

PMID- 27887620
TI  - Anatomy meets dentistry! Linking anatomy and clinical practice in the preclinical
      dental curriculum.
AB  - BACKGROUND: Establishing a strong link early on between preclinical coursework
      and the clinical context is necessary for students to be able to recognize the
      practical relevance of the curriculum during their preclinical anatomical courses
      and to transfer knowledge more easily. Our objective was to enhance the clinical
      relevance of a preclinical anatomy course for second-year medical students of
      dentistry by implementing an interdisciplinary skills training course on
      "Palpation of the Head and Neck Muscles" and to measure the learning outcomes.
      METHODS: For the curricular development of the expanded course module, Kern's 6
      step approach was applied including subjective evaluation. We used a peer
      teaching format supported by an e-learning application. A randomized control
      study measured effects of the two components (skills training, e-module) on
      learning outcomes. Four learning methods were compared: (1) lecture, (2) lecture
      + e-module, (3) lecture + skills training, (4) lecture + skills training + e
      module. An objective structured clinical examination (OSCE) was used to measure
      and compare learning outcomes. RESULTS: The two-way variance analysis
      demonstrated that participation in the skills training had a statistically
      significant effect on the OSCE results (p = 0.0007). Students who participated in
      the skills training did better (phi 107.4 +/- 14.4 points) than students who only
      attended the lecture (phi 88.8 +/- 26.2 points). Students who used the e-module
      but did not attend the skills training earned a slightly but not significantly
      higher average number of points (phi 91.8 +/- 31.3 points) than those who only
      attended the lecture. The learning outcomes of the skills training were again
      significantly increased when the training was combined with the e-module (phi
      121.8 +/- 21.8 points), thus making it the ideal method for achieving the
      learning objectives defined in this study. CONCLUSIONS: The "Palpation of the
      Head and Neck Muscles" interdisciplinary skills training course linking basic
      anatomical knowledge and clinical skills led to clearly improved learning
      outcomes for both, anatomical knowledge and clinical skills. The additional use
      of an e-learning tool (e-module) improved the learning effect.

PMID- 27887622
TI  - Learning to care: medical students' reported value and evaluation of palliative
      care teaching involving meeting patients and reflective writing.
AB  - BACKGROUND: Over recent years there has been an increase in teaching of both
      palliative care and reflective practice in UK medical schools. The palliative
      care teaching at the University of Cambridge School of Clinical Medicine is multi
      faceted and involves students writing reflective essays after individually
      meeting patients approaching the end of life during their final year general
      practice and hospital medicine placements. This paper draws on two studies
      examining this teaching element to analyse what the students found valuable about
      it and to comment on the practice of meeting patients and subsequent reflective
      writing. METHODS: Two studies have explored students' perceptions of these course
      components. The first was a thematic analysis of 234 reflective essays from 123
      students written in 2007-2008, including examining what students wrote about the
      exercise itself. The second project involved a semi-structured questionnaire that
      students completed anonymously; this paper reports on the free text elements of
      that study [sample size =107]. Since similar themes were found in both studies,
      the coding structures from each project were compared and combined, enabling
      triangulation of the findings around what the students found valuable from the
      palliative care teaching involving meeting patients and reflective writing.
      RESULTS: Overall, students reported that these components of the palliative care
      teaching are valuable. Four main themes were identified as aspects that students
      valued: (1) dedicated time with patients, (2) learning about wider elements of
      treatment and holistic care, (3) practicing communication skills, and (4)
      learning about themselves through reflective writing. Some students expressed a
      dislike for having to formally write a reflective essay. CONCLUSION: It is
      possible to arrange for all of the medical students to individually meet at least
      two patients receiving palliative or end of life care. Students found these
      encounters valuable and many wrote about the benefit of formally writing about
      these experiences. Students reported finding this model useful in widening their
      skill-set and understanding of palliative care.

PMID- 27887621
TI  - Pediatric emergency department visits and ambient Air pollution in the U.S. State
      of Georgia: a case-crossover study.
AB  - BACKGROUND: Estimating the health effects of ambient air pollutant mixtures is
      necessary to understand the risk of real-life air pollution exposures. METHODS:
      Pediatric Emergency Department (ED) visit records for asthma or wheeze (n =
      148,256), bronchitis (n = 84,597), pneumonia (n = 90,063), otitis media (n =
      422,268) and upper respiratory tract infection (URI) (n = 744,942) were obtained
      from Georgia hospitals during 2002-2008. Spatially-contiguous daily
      concentrations of 11 ambient air pollutants were estimated from CMAQ model
      simulations that were fused with ground-based measurements. Using a case
      crossover study design, odds ratios for 3-day moving average air pollutant
      concentrations were estimated using conditional logistic regression, matching on
      ZIP code, day-of-week, month, and year. RESULTS: In multipollutant models, the
      association of highest magnitude observed for the asthma/wheeze outcome was with
      "oxidant gases" (O3, NO2, and SO2); the joint effect estimate for an IQR increase
      of this mixture was OR: 1.068 (95% CI: 1.040, 1.097). The group of "secondary
      pollutants" (O3 and the PM2.5 components SO42-, NO3-, and NH4+) was strongly
      associated with bronchitis (OR: 1.090, 95% CI: 1.050, 1.132), pneumonia (OR:
      1.085, 95% CI: 1.047, 1.125), and otitis media (OR: 1.059, 95% CI: 1.042, 1.077).
      ED visits for URI were strongly associated with "oxidant gases," "secondary
      pollutants," and the "criteria pollutants" (O3, NO2, CO, SO2, and PM2.5).
      CONCLUSIONS: Short-term exposures to air pollution mixtures were associated with
      ED visits for several different pediatric respiratory diseases.

PMID- 27887623
TI  - Generation of protective immunity against Orientia tsutsugamushi infection by
      immunization with a zinc oxide nanoparticle combined with ScaA antigen.
AB  - BACKGROUND: Zinc oxide nanoparticle (ZNP) has been applied in various biomedical
      fields. Here, we investigated the usage of ZNP as an antigen carrier for vaccine
      development by combining a high affinity peptide to ZNP. RESULTS: A novel zinc
      oxide-binding peptide (ZBP), FPYPGGDA, with high affinity to ZNP (K a  = 2.26 *
      106 M-1) was isolated from a random peptide library and fused with a bacterial
      antigen, ScaA of Orientia tsutsugamushi, the causative agent of scrub typhus. The
      ZNP/ZBP-ScaA complex was efficiently phagocytosed by a dendritic cell line,
      DC2.4, in vitro and significantly enhanced anti-ScaA antibody responses in vivo
      compared to control groups. In addition, immunization with the ZNP/ZBP-ScaA
      complex promoted the generation of IFN-gamma-secreting T cells in an antigen
      dependent manner. Finally, we observed that ZNP/ZBP-ScaA immunization provided
      protective immunity against lethal challenge of O. tsutsugamushi, indicating that
      ZNP can be used as a potent adjuvant when complexed with ZBP-conjugated antigen.
      CONCLUSIONS: ZNPs possess good adjuvant potential as a vaccine carrier when
      combined with an antigen having a high affinity to ZNP. When complexed with ZBP
      ScaA antigen, ZNPs could induce strong antibody responses as well as protective
      immunity against lethal challenges of O. tsutsugamushi. Therefore, application of
      ZNPs combined with a specific soluble antigen could be a promising strategy as a
      novel vaccine carrier system.

PMID- 27887624
TI  - Detection and phylogenetic analysis of porcine epidemic diarrhea virus in central
      China based on the ORF3 gene and the S1 gene.
AB  - BACKGROUND: Porcine epidemic diarrhea (PED) has increased in severity in China
      since 2010. To investigate further the infectivity, genetic diversity and
      molecular epidemiology of its causative agent, the porcine epidemic diarrhea
      virus (PEDV), we assessed 129 clinical samples, which were the intestinal tissue
      of piglets with severe diarrhea, from 17 cities in central China. Both the spike
      (S) glycoprotein (S1, 1-789 amino acids (aa)) and the full-length ORF3 gene of 21
      representative field strains from 21 farms in 11 cities were sequenced and
      analysed. METHODS: PEDV was detected by reverse transcription-polymerase chain
      reaction (RT-PCR), and S1 and ORF3 sequences were processed by the Clustal W
      method via DNAMAN 8 software, and phylogenetic trees were constructed by the
      neighbor-joining method using MEGA 6 software. RESULTS: The prevalence of PEDV
      was 92.25% and was detected in 119 of 129 samples, with 94.03% (63 of 67) of pig
      farms harbouring the disease. According to the phylogenetic analysis of the S1
      genes, our isolates all fell into group G2 (variants) and showed a close
      relationship to isolates from Chinese (HN1303, CH/ZMDZY/11 and AJ1102), Korean
      (AD01), American (MN, IA1, IA2 and 13-019349) sources, and these isolates
      differed genetically from other Chinese (LZC, CH/HNZZ/2011 and SD-M) and Korean
      (SM98) strains as well Japanese (83-P5 and MK) strains. In addition, our isolates
      differed from attenuated vaccine strains, CV777 (used in China) and DR13 (used in
      Korea). According to our derived amino acid sequence analysis, we detected one
      novel variant PEDV, viz: CH/HNLY, with 4-aa insertion/deletion (RSSS/T) at
      position 375 and 1-aa (D) deletion at position 430 compared to the CV777
      attenuated strain. These mutations were located on the receptor binding domain.
      Our ORF3 gene analyses showed that the prevalent PEDV isolates were variants, and
      the isolated strains differed genetically from the vaccine strains. CONCLUSIONS:
      These findings illustrated the existence of genetic diversity among
      geographically distinct PEDV strains, and our study has provided an impetus to
      conduct further research on the PEDV receptor binding protein and on the new and
      efficacious vaccines design.

PMID- 27887625
TI  - The impact of temperature and precipitation on blacklegged tick activity and Lyme
      disease incidence in endemic and emerging regions.
AB  - BACKGROUND: The incidence of Lyme disease shows high degrees of inter-annual
      variation in the northeastern United States, but the factors driving this
      variation are not well understood. Complicating matters, it is also possible that
      these driving factors may vary in regions with differing histories of Lyme
      disease endemism. We evaluated the effect of the number of hot (T > 25  degrees
      C), dry (precipitation = 0) days during the questing periods of the two immature
      Ixodes scapularis life stages (larval and nymphal) on inter-annual variation in
      Lyme disease incidence between 2000 and 2011 in long-term endemic versus recently
      endemic areas. We also evaluated the effect of summer weather on tick questing
      activity and the number of ticks found on small mammals between 1994 and 2012 on
      six sites in Millbrook, NY. RESULTS: The number of hot, dry days during the
      larval period of the previous year did not affect the human incidence of Lyme
      disease or the density of questing nymphs the following season. However, dry
      summer weather during the nymphal questing period had a significant negative
      effect on the incidence of Lyme disease in the long-term endemic areas, and on
      the density of questing nymphs. Summer weather conditions had a more pronounced
      effect on actively questing I. scapularis collected via dragging than on the
      number of ticks found feeding on small mammals. In recently endemic areas Lyme
      disease incidence increased significantly over time, but no trend was detected
      between disease incidence and dry summer weather. CONCLUSIONS: Recently endemic
      regions showed an increase in Lyme disease incidence over time, while incidence
      in long-term endemic regions appears to have stabilized. Only within the
      stabilized areas were we able to detect reduced Lyme disease incidence in years
      with hot, dry summer weather. These patterns were reflected in our field data,
      which showed that questing activity of nymphal I. scapularis was reduced by hot,
      dry summer weather.

PMID- 27887626
TI  - Expression and processing analyses of wild type and p.R47H TREM2 variant in
      Alzheimer's disease brains.
AB  - BACKGROUND: Genetic analyses showed that the triggering receptor expressed in
      myeloid cells 2 (TREM2) p.R47H variant increases the risk for Alzheimer's disease
      (AD). The question of whether the p.R47H mutation affects expression or function
      of the receptor remains unanswered. To address this question we quantified mRNA
      and analyzed protein profiles of WT and p.R47H TREM2 in human brains. METHODS:
      Quantitative real-time PCR (qPCR) was performed using 2 sets of primers one that
      detects all TREM2 mRNA isoforms and one specific for the alternative spliced
      isoform (TREM2alt) that encodes for the extracellular domain (soluble TREM2).
      Because in the brain TREM2 is expressed primarily in microglial cells, we also
      assessed the levels of IBA1 to control for microglial variability across samples.
      For TREM2 protein quantitation and N-glycosylation processing, RIPA brain
      extracts were analyzed by Western blot before and after EndoH and PNGaseF
      treatments. RESULTS: We identified statistically significant increased levels of
      TREM2 transcripts in the temporal cortex of AD subjects when compared with
      controls; TREM2alt was likewise higher in AD cases, but was not significant after
      adjustment for covariates. Quantitative analysis of TREM2 protein confirmed qPCR
      results that showed higher levels in AD than in control brains. Among AD
      subjects, we observed a trend towards higher mRNA and protein TREM2 levels in
      carriers of the p.R47H risk allele. Analysis of individual TREM2 species found no
      difference in the relative amounts of mature and immature species, and carboxyl
      terminal fragments between non carriers and p.R47H samples. Furthermore, TREM2
      species from either non carriers or p.R47H brains were equally susceptible to
      EndoH and PNGaseF treatments. CONCLUSIONS: Our results suggest that TREM2
      expression is increased in AD. Furthermore, we provide evidence indicating that
      p.R47H mutation does not affect the levels of TREM2 either directly by altering
      expression or indirectly by affecting processing of the protein. Our data support
      previous findings that suggest that p.R47H variant affects TREM2 function by
      altering binding properties of the receptor rather than expression.

PMID- 27887627
TI  - EphA5 protein, a potential marker for distinguishing histological grade and
      prognosis in ovarian serous carcinoma.
AB  - BACKGROUND: Ovarian serous carcinoma (OSC) is the most common ovarian epithelial
      malignancy. Disregulation of Eph/ephrin signaling has been implicated in
      oncogenesis and tumor progression. EphA5 receptor is one of large families of Eph
      tyrosine kinase receptor and is documented in the development of nervous system.
      Till now, there is no published data about the role of EphA5 in ovarian
      epithelial neoplasmas. METHODS: This study aims to investigate the expression of
      EphA5 protein in ovarian serous carcinoma, and its relationship to clinical
      pathological characteristics. Sixty-one cases of ovarian serous carcinoma, 24
      cases of benign ovarian serous tumors, 42 cases of serous borderline tumors and
      20 cases of normal fallopian tubes were examined using immunohistochemical
      staining. The relationship between EphA5 expression and pathological parameters
      was analyzed. Kaplan-Meier survival function was used to analyze prognosis of
      patients. RESULTS: Immunostaining analysis demonstrated that the EphA5 protein
      was highly expressed in 100% (20/20) of normal fallopian tube samples, 100%
      (24/24) of benign epithelial ovarian tumors, 76% (32/42) of ovarian serous
      borderline tumors, and 31% (19/61) of ovarian serous carcinomas. Loss of
      EphA5expression was associated with tumor grade (P < 0.001) and FIGO stage (P =
      0.005). The survival analysis showed that patients with negative or weak
      expression of EphA5 protein had a poor outcome than those with positive
      expression (P = 0.004). CONCLUSIONS: Our results show that EphA5 may be a
      potential biomarker for distinguishing high-and low-grade ovarian serous
      carcinoma and a potential prognostic marker.

PMID- 27887628
TI  - Implications of vessel co-option in sorafenib-resistant hepatocellular carcinoma.
AB  - The reason why tumors generally have a modest or transient response to
      antiangiogenic therapy is not well understood. This poses a major challenge for
      sorafenib treatment of advanced hepatocellular carcinoma (HCC) where alternate
      therapies are lacking. We recently published a paper entitled "Co-option of liver
      vessels and not sprouting angiogenesis drives acquired sorafenib resistance in
      hepatocellular carcinoma" in the Journal of the National Cancer Institute,
      providing a potential explanation for this limited benefit. We found that in mice
      bearing HCCs that had acquired resistance to sorafenib, tumors had switched from
      using angiogenesis for growth to co-opting the liver vasculature by becoming more
      invasive. Accumulating evidence suggests that many human tumor types may use
      vessel co-option, which has profound implications for the use of anti-angiogenic
      agents for cancer treatment.

PMID- 27887629
TI  - The Oxford Nanopore MinION: delivery of nanopore sequencing to the genomics
      community.
AB  - Nanopore DNA strand sequencing has emerged as a competitive, portable technology.
      Reads exceeding 150 kilobases have been achieved, as have in-field detection and
      analysis of clinical pathogens. We summarize key technical features of the Oxford
      Nanopore MinION, the dominant platform currently available. We then discuss
      pioneering applications executed by the genomics community.

PMID- 27887630
TI  - Immunohistochemical insights into Saffold virus infection of the brain of
      juvenile AG129 mice.
AB  - BACKGROUND: Saffold Virus (SAFV) is a human cardiovirus that is suspected of
      causing infection of the central nervous system (CNS) in children. While recent
      animal studies have started to elucidate the pathogenesis of SAFV, very little is
      known about the mechanisms behind it. METHOD: In this study, we attempted to
      elucidate some of the mechanisms of the pathogenesis of SAFV in the brain of a
      juvenile mouse model by using immunohistochemical methods. RESULTS: We first
      showed that SAFV is able to infect both neuronal and glial cells in the brain of
      2 week-old AG129 mice. We then showed that SAFV is able to induce apoptosis in
      both neuronal and glial cells in the brain. Lastly, we showed that SAFV infection
      does not show any signs of gross demyelination in the brain. CONCLUSION: Overall,
      our results provide important insights into the mechanisms of SAFV in the brain.

PMID- 27887631
TI  - The complexities and caveats of lineage tracing in the mammary gland.
AB  - Lineage tracing is increasingly being utilised to probe different cell types that
      exist within the mammary gland. Whilst this technique is powerful for tracking
      cells in vivo and dissecting the roles of different cellular subsets in
      development, homeostasis and oncogenesis, there are important caveats associated
      with lineage tracing strategies. Here we highlight key parameters of particular
      relevance for the mammary gland. These include tissue preparation for whole-mount
      imaging, whereby the inclusion of enzymatic digestion can drastically alter
      tissue architecture and cell morphology, and therefore should be avoided. Other
      factors include the scoring of clones in three dimensions versus two dimensions,
      the timing of induction, and the marked variability in labelling efficiency that
      is evident not only between different mouse models harbouring a similar gene
      promoter but also within a given strain and even within a single mammary gland.
      Thus, it becomes crucial to visualise extensive areas of ductal tissue and to
      consider the intricacies of the methodology for lineage tracing studies on normal
      mammary development and on potential 'cells of origin' of cancer.

PMID- 27887632
TI  - Adjuvant therapies in advanced hepatocellular carcinoma: moving forward from the
      STORM.
AB  - : Like other previous treatments and approaches, sorafenib, an antiangiogenic
      drug, failed to show any benefit in the adjuvant setting for hepatocellular
      carcinoma in a large clinical trial. We discuss reasons and implications of these
      negative results and the implications for clinical practice and future research.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT00692770 . Registered 5 June 2008.
      This study has been completed.

PMID- 27887633
TI  - Antitumor activity of TY-011 against gastric cancer by inhibiting Aurora A,
      Aurora B and VEGFR2 kinases.
AB  - BACKGROUND: Overexpression of Aurora A and B has been reported in a wide range of
      tumor types, including gastric cancer. Anti-angiogenesis has been considered as
      an important therapeutic modality in advanced gastric cancer. Here we identified
      a novel compound TY-011 with promising antitumor activity by targeting mitotic
      kinases (Aurora A and B) and angiogenic receptor tyrosine kinase (VEGFR2).
      METHODS: HTRF(r) KinEASETM assay was used to detect the effect of TY-011 against
      Aurora A, Aurora B and VEGFR2 activities. Docking simulation study was performed
      to predict the binding mode of TY-011 with Aurora A and B kinases. CCK-8 assay
      was used to test cell growth. Cell cycle and cell apoptosis was analyzed by flow
      cytometry. Gastric cancer cell xenograft mouse models were used for in vivo
      study. TUNEL kit was used to determine the apoptosis of tumor tissues.
      Immunohistochemistry analysis and HUVEC tube formation assay were performed to
      determine the anti-angiogenesis ability. Immunofluorescence and western blot were
      used to test protein expression. RESULTS: TY-011 was identified as a potential
      Aurora A and B inhibitor by HTRF(r) KinEASETM assay. It effectively inhibited
      cellular Aurora A and B activities in a concentration-dependent manner. TY-011
      occupied the ATP-binding site of both Aurora A and B kinases. TY-011 demonstrated
      prominent inhibitory effects on proliferation of gastric cancer cells. TY-011
      treatment induced an obvious accumulation of cells at G2/M phase and a modest
      increase of cells with >4 N DNA content, which then underwent apoptosis.
      Meaningfully, orally administration of TY-011 demonstrated superior efficacy
      against the tumor growth in gastric cancer cell xenograft, with ~90% inhibition
      rate and 100% tumor regression at 9 mg/kg dose, and TY-011 did not affect the
      body weight of mice. Interestingly, we observed that TY-011 also antagonized
      tumor angiogenesis by targeting VEGFR2 kinase. CONCLUSIONS: These results
      indicate that TY-011 is a well-tolerated, orally active compound that targets
      mitosis and angiogenesis in tumor growth, and provides strong preclinical support
      for use as a therapeutic for human gastric cancers.

PMID- 27887634
TI  - Mental contrasting as a behaviour change technique: a systematic review protocol
      paper of effects, mediators and moderators on health.
AB  - BACKGROUND: Mental contrasting is a self-regulation strategy that is required for
      strong goal commitment. In mental contrasting, individuals firstly imagine a
      desired future or health goal that contrasted with the reality proceeding the
      goal state, which after reflection is viewed as an obstacle (Oettingen et al. J
      Pers Soc Psychol 80:736-753, 2001). Mentally contrasting a positive future with
      reality enables individuals to translate positive attitudes and high efficacy
      into strong goal commitment. METHODS: A systematic review of the literature is
      proposed to explore the efficacy of mental contrasting as a behaviour change
      technique (Michie et al., Ann Behav Med 46: 81-95, 2013) for health. The review
      also aims to identify the effects of mental contrasting on health-related
      behaviour, as well as identifying mediator and moderator variables. DISCUSSION:
      This will be the first systematic review of mental contrasting as a health
      behaviour change technique. With sufficient studies, a meta-analysis will be
      conducted with sensitivity and sub group analyses. If meta-analysis is not
      appropriate, a narrative synthesis of the reviewed studies will be conducted.
      SYSTEMATIC REVIEW REGISTRATION: Review protocol registered on PROSPERO reference
      CRD42016034202 .

PMID- 27887635
TI  - Anisakis pegreffii (Nematoda: Anisakidae) products modulate oxidative stress and
      apoptosis-related biomarkers in human cell lines.
AB  - BACKGROUND: In countries with elevated prevalence of zoonotic anisakiasis and
      high awareness of this parasitosis, a considerable number of cases that associate
      Anisakis sp. (Nematoda, Anisakidae) and different bowel carcinomas have been
      described. Although neoplasia and embedded larvae were observed sharing the
      common site affected by chronic inflammation, no association between the nematode
      and malignancy were directly proved. Similarly, no data are available about the
      effect of secretory and excretory products of infecting larvae at the host's
      cellular level, except in respect to allergenic interaction. METHODS: To test the
      mechanisms by which human non-immune cells respond to the larvae, we exposed the
      fibroblast cell line HS-68 to two Anisakis products (ES, excretory/secretory
      products; and EC, crude extract) and evaluated molecular markers related to
      stress response, oxidative stress, inflammation and apoptosis, such as p53,
      HSP70, TNF-alpha, c-jun and c-fos, employing cell viability assay,
      spectrophotometry, immunoblotting and qPCR. RESULTS: Both Anisakis products led
      to increased production of reactive oxygen species (ROS), especially in EC
      treated cells. While the ES treatment induces activation of kinases suggesting
      inflammation and cell proliferation (or inhibition of apoptosis), in EC-treated
      cells, other signaling pathways indicate the inhibition of apoptosis, marked by
      strong upregulation of Hsp70. Elevated induction of p53 in fibroblasts treated by
      both Anisakis products, suggests a significantly negative effect on the host DNA.
      CONCLUSIONS: This study shows that in vitro cell response to Anisakis products
      can result in at least two different scenarios, which in both cases lead to
      inflammation and DNA damage. Although these preliminary results are far from
      proving a relationship between the parasite and cancer, they are the first to
      support the existence of conditions where such changes are feasible.

PMID- 27887636
TI  - Development and validation of a nomogram for predicting the survival of patients
      with non-metastatic nasopharyngeal carcinoma after curative treatment.
AB  - BACKGROUND: The TNM staging system is far from perfect in predicting the survival
      of individual cancer patients because only the gross anatomy is considered. The
      survival rates of the patients who have the same TNM stage disease vary across a
      wide spectrum. This study aimed to develop a nomogram that incorporates other
      clinicopathologic factors for predicting the overall survival (OS) of non
      metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments.
      METHODS: We retrospectively collected the clinical data of 1520 NPC patients who
      were diagnosed histologically between November 2000 and September 2003. The
      clinical data of a separate cohort of 464 patients who received intensity
      modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to
      examine the extensibility of the model. Cox regression analysis was used to
      identify the prognostic factors for building the nomogram. The predictive
      accuracy and discriminative ability were measured using the concordance index (c
      index). RESULTS: We identified and incorporated 12 independent clinical factors
      into the nomogram. The calibration curves showed that the prediction of OS was in
      good agreement with the actual observation in the internal validation set and
      IMRT cohort. The c-index of the nomogram was statistically higher than that of
      the 7th edition TNM staging system for predicting the survival in both the
      primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63). CONCLUSION:
      We developed and validated a novel nomogram that outperformed the TNM staging
      system in predicting the OS of non-metastatic NPC patients who underwent curative
      therapy.

PMID- 27887637
TI  - Clinical improvement and reduction in serum calprotectin levels after an
      intensive exercise programme for patients with ankylosing spondylitis and non
      radiographic axial spondyloarthritis.
AB  - BACKGROUND: The efficacy of exercise therapy for ankylosing spondylitis (AS) is
      well-documented, but dearth of information is for non-radiographic axial
      spondyloarthritis (nr-axSpA). Biomarkers like serum calprotectin, interleukins IL
      6, IL-17 and tumour necrosis factor (TNF)-alpha may reflect the disease activity
      of axial spondyloarthritis (axSpA). In this study, we investigated clinical and
      laboratory parameters of both axSpA subgroups in response to intensive physical
      exercise. METHODS: Altogether, 46 patients with axSpA, characterised according to
      the Assessment of SpondyloArthritis International Society criteria as having nr
      axSpA or AS underwent 6-month exercise programme. Clinical outcomes of disease
      activity, Bath AS Disease Activity Index (BASDAI), AS Disease Activity Index
      (ASDAS-CRP), mobility, Bath AS Metrology Index (BASMI) and function, Bath AS
      Functional Index (BASFI) were evaluated at baseline and at the end of the
      exercise programme. Serum IL-6 and IL-17, TNF-alpha and calprotectin were
      measured via ELISA. The clinical and laboratory data of 29 control axSpA patients
      were used for the evaluation of the results. RESULTS: In all axSpA patients, the
      ASDAS-CRP (2.10 +/- 0.12 to 1.84 +/- 0.11, p <0.01) and BASMI (1.28 +/- 0.14 to
      0.66 +/- 0.84, p <0.0001) improved after 6 months of exercise therapy. There was
      a significant improvement in the ASDAS-CRP in the nr-axSpA subgroup (2.01 +/-
      0.19 to 1.73 +/- 0.16, p <0.05) and in the BASMI in both, the nr-axSpA and the AS
      subgroups (1.09 +/- 0.12 to 0.47 +/- 0.08, p <0.0001 and 1.43 +/- 0.24 to 0.82 +/
      0.23, p <0.0001, respectively). Both, ASDAS-CRP and BASDAI, were significantly
      improved in the exercise axSpA group compared to the control axSpA group (mean 
      0.26 vs. -0.13 and -0.49 vs. 0.12, respectively, all p <0.05). Only calprotectin
      was significantly reduced after the exercise programme in nr-axSpA and AS
      patients (from 2379.0 +/- 243.20 to 1779.0 +/- 138.30 MUg/mL and from 2430.0 +/-
      269.70 to 1816.0 +/- 148.20 MUg/mL, respectively, all p <0.01). The change in
      calprotectin was more profound in the axSpA intervention group (mean -604.56)
      than in the control axSpA (mean -149.28, p <0.05). CONCLUSION: This study
      demonstrated similar efficacy for an intensive exercise programme in both nr
      axSpA and AS patients. A significant decrease in serum calprotectin levels in
      both subgroups of axSpA patients after the exercise programme reflected an
      improvement in the disease activity and spinal mobility.

PMID- 27887638
TI  - Mitochondrial replacement approaches: challenges for clinical implementation.
AB  - The advent of mitochondrial replacement techniques poses many scientific,
      regulatory, and ethical questions. Previous studies suggest good safety and
      efficacy profiles of these techniques, but challenges remain for clinical
      implementation and international consensus is needed on the regulation of these
      approaches.

PMID- 27887639
TI  - Prevalence, sensitivity and specificity of antibodies against carbamylated
      proteins in a monocentric cohort of patients with rheumatoid arthritis and other
      autoimmune rheumatic diseases.
AB  - BACKGROUND: Antibodies against carbamylated proteins (anti-CarP) have been
      recently identified in the sera of patients with rheumatoid arthritis (RA). The
      objective of the study was to evaluate the prevalence, sensitivity and
      specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA)
      and rheumatoid factor (RF), replicating the existing data in a large cohort of
      Italian patients with RA and extending the evaluation to other autoimmune
      rheumatic diseases (AIRDs). METHODS: Serum samples (n = 607) from 309 patients
      with RA, 200 disease controls and 98 normal healthy subjects (NHS) were
      evaluated. Anti-CarP were detected using carbamylated fetal calf serum as the
      antigen. ACPAs were detected using second-generation ELISA and IgM RF was
      assessed as part of routine analysis. RESULTS: Anti-CarP antibodies were detected
      in 117 patients with RA (34.4%), ACPA in 190 patients (61.4%) and RF in 202
      patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS
      (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among
      disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA
      in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of
      patients with systemic lupus erythematosus and 31.1% of patients with Sjogren
      syndrome were positive for anti-CarP. The sensitivity of anti-CarP, ACPA and RF
      was 46.8%, 61.8% and 64.4%, respectively and specificity was 91.95%, 89.93% and
      76.51%, respectively. CONCLUSIONS: The present study extends the knowledge of
      anti-CarP antibodies, confirming previous data on the diagnostic accuracy of anti
      CarP in RA in a large cohort of Italian patients. Anti-CarP antibodies
      demonstrated relatively low sensitivity and slightly higher specificity compared
      to ACPA and RF. Even if predominantly present in RA, anti-CarP was detected in a
      variable percentage of patients with other autoimmune rheumatic diseases and
      their generation could be attributed to the inflammatory status; the clinical
      relevance of anti-CarP antibodies in these latter patients should be further
      determined.

PMID- 27887640
TI  - Functional and regulatory profiling of energy metabolism in fission yeast.
AB  - BACKGROUND: The control of energy metabolism is fundamental for cell growth and
      function and anomalies in it are implicated in complex diseases and ageing.
      Metabolism in yeast cells can be manipulated by supplying different carbon
      sources: yeast grown on glucose rapidly proliferates by fermentation, analogous
      to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon
      sources metabolism shifts towards respiration. RESULTS: We screened deletion
      libraries of fission yeast to identify over 200 genes required for respiratory
      growth. Growth media and auxotrophic mutants strongly influenced respiratory
      metabolism. Most genes uncovered in the mutant screens have not been implicated
      in respiration in budding yeast. We applied gene-expression profiling approaches
      to compare steady-state fermentative and respiratory growth and to analyse the
      dynamic adaptation to respiratory growth. The transcript levels of most genes
      functioning in energy metabolism pathways are coherently tuned, reflecting
      anticipated differences in metabolic flows between fermenting and respiring
      cells. We show that acetyl-CoA synthase, rather than citrate lyase, is essential
      for acetyl-CoA synthesis in fission yeast. We also investigated the
      transcriptional response to mitochondrial damage by genetic or chemical
      perturbations, defining a retrograde response that involves the concerted
      regulation of distinct groups of nuclear genes that may avert harm from
      mitochondrial malfunction. CONCLUSIONS: This study provides a rich framework of
      the genetic and regulatory basis of energy metabolism in fission yeast and
      beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for
      investigating metabolism. As a model for cellular energy regulation, fission
      yeast provides an attractive and complementary system to budding yeast.

PMID- 27887641
TI  - Structural divergence of chromosomes between malaria vectors Anopheles lesteri
      and Anopheles sinensis.
AB  - BACKGROUND: Anopheles lesteri and Anopheles sinensis are two major malaria
      vectors in China and Southeast Asia. They are dramatically different in terms of
      geographical distribution, host preference, resting habitats, and other traits
      associated with ecological adaptation and malaria transmission. Both species
      belong to the Anopheles hyrcanus group, but the extent of genetic differences
      between them is not well understood. To provide an effective way to differentiate
      between species and to find useful markers for population genetics studies, we
      performed a comparative cytogenetic analysis of these two malaria vectors.
      RESULTS: Presented here is a standard cytogenetic map for An. lesteri, and a
      comparative analysis of chromosome structure and gene order between An. lesteri
      and An. sinensis. Our results demonstrate that much of the gene order on
      chromosomes X and 2 was reshuffled between the two species. However, the banding
      pattern and the gene order on chromosome 3 appeared to be conserved. We also
      found two new polymorphic inversions, 2Lc and 3Rb, in An. lesteri, and we mapped
      the breakpoints of these two inversions on polytene chromosomes. CONCLUSIONS: Our
      results demonstrate the extent of structural divergence of chromosomes between
      An. lesteri and An. sinensis, and provide a new taxonomic cytogenetic tool to
      distinguish between these two species. Polymorphic inversions of An. lesteri
      could serve as markers for studies of the population structure and ecological
      adaptations of this major malaria vector.

PMID- 27887642
TI  - Rapid scoring of genes in microbial pan-genome-wide association studies with
      Scoary.
AB  - Genome-wide association studies (GWAS) have become indispensable in human
      medicine and genomics, but very few have been carried out on bacteria. Here we
      introduce Scoary, an ultra-fast, easy-to-use, and widely applicable software tool
      that scores the components of the pan-genome for associations to observed
      phenotypic traits while accounting for population stratification, with minimal
      assumptions about evolutionary processes. We call our approach pan-GWAS to
      distinguish it from traditional, single nucleotide polymorphism (SNP)-based GWAS.
      Scoary is implemented in Python and is available under an open source GPLv3
      license at https://github.com/AdmiralenOla/Scoary .

PMID- 27887643
TI  - Distribution of FDG-avid nodes in esophageal cancer: implications for
      radiotherapy target delineation.
AB  - PURPOSE: Clinical target volumes (CTV) for radiotherapy (RT) in esophageal cancer
      (EC) are based on standard expansions of primary tumor volume. Data is needed to
      define regions at highest risk for occult disease, based on histology and
      location of the primary tumor. We therefore reviewed PET scans in EC patients to
      characterize the location of FDG-avid lymph node metastases (LNM). MATERIALS AND
      METHODS: We identified 473 EC patients with reviewable pre-treatment PET-CT
      scans. Tumors were classified by histology and location; 85% were distal or GE
      junction tumors and 71% were adenocarcinoma. FDG-avid LNM were classified using
      standard radiographic nodal atlases, and distances from primary tumor to
      paraesophageal LNM were also measured. RESULTS: The most common LNM in upper EC
      were supraclavicular, retrotracheal and paratracheal. The most common LNM in
      lower EC were paraesophageal and in the gastrohepatic space. Overall, 55% of
      paraesophageal LNM were adjacent to primary tumor. Of upper esophageal tumors
      with paraesophageal LNM, 87% were adjacent to the tumor and none were >6 cm from
      tumor. However, 57% of lower esophageal tumors with paraesophageal LNM had non
      adjacent paraesophageal nodes, 24% of which were >8 cm from the tumor.
      CONCLUSION: A more data-driven and individualized approach to CTV delineation
      could improve the therapeutic ratio of RT in esophageal cancer. These results can
      guide CTV delineation by indicating the potential distribution of nodal
      involvement in esophageal cancer.

PMID- 27887644
TI  - Copenhagen comorbidity in HIV infection (COCOMO) study: a study protocol for a
      longitudinal, non-interventional assessment of non-AIDS comorbidity in HIV
      infection in Denmark.
AB  - BACKGROUND: Modern combination antiretroviral therapy (cART) has improved
      survival for people living with HIV (PLWHIV). Non-AIDS comorbidities have
      replaced opportunistic infections as leading causes of mortality and morbidity,
      and are becoming a key health concern as this population continues to age. The
      aim of this study is to estimate the prevalence and incidence of non-AIDS
      comorbidity among PLWHIV in Denmark in the cART era and to determine risk factors
      contributing to the pathogenesis. The study primarily targets cardiovascular,
      respiratory, and hepatic non-AIDS comorbidity. METHODS/DESIGN: The Copenhagen
      comorbidity in HIV-infection (COCOMO) study is an observational, longitudinal
      cohort study. The study was initiated in 2015 and recruitment is ongoing with the
      aim of including 1500 PLWHIV from the Copenhagen area. Follow-up examinations
      after 2 and 10 years are planned. Uninfected controls are derived from the
      Copenhagen General Population Study (CGPS), a cohort study including 100,000
      uninfected participants from the same geographical region. Physiological and
      biological measures including blood pressure, ankle-brachial index,
      electrocardiogram, spirometry, exhaled nitric oxide, transient elastography of
      the liver, computed tomography (CT) angiography of the heart, unenhanced CT of
      the chest and upper abdomen, and a number of routine biochemical analysis are
      uniformly collected in participants from the COCOMO study and the CGPS. Plasma,
      serum, buffy coat, peripheral blood mononuclear cells (PBMC), urine, and stool
      samples are collected in a biobank for future studies. Data will be updated
      through periodical linking to national databases. DISCUSSION: As life expectancy
      for PLWHIV improves, it is essential to study long-term impact of HIV and cART.
      We anticipate that findings from this cohort study will increase knowledge on non
      AIDS comorbidity in PLWHIV and identify targets for future interventional trials.
      Recognizing the demographic, clinical and pathophysiological characteristics of
      comorbidity in PLWHIV may help inform development of new guidelines and enable us
      to move forward to a more personalized HIV care. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT02382822 .

PMID- 27887645
TI  - Resource utilisation, costs and clinical outcomes in non-institutionalised
      patients with Alzheimer's disease: 18-month UK results from the GERAS
      observational study.
AB  - BACKGROUND: Alzheimer's disease (AD), the commonest cause of dementia, represents
      a significant cost to UK society. This analysis describes resource utilisation,
      costs and clinical outcomes in non-institutionalised patients with AD in the UK.
      METHODS: The GERAS prospective observational study assessed societal costs
      associated with AD for patients and caregivers over 18 months, stratified
      according to baseline disease severity (mild, moderate, or moderately
      severe/severe [MS/S]). All patients enrolled had an informal caregiver willing to
      participate in the study. Healthcare resource utilisation was measured using the
      Resource Utilization in Dementia instrument, and 18-month costs estimated by
      applying unit costs of services and products (2010 values). Total societal costs
      were calculated using an opportunity cost approach. RESULTS: Overall, 526
      patients (200 mild, 180 moderate and 146 MS/S at baseline) were recruited from 24
      UK centres. Mini-Mental State Examination (MMSE) scores deteriorated most
      markedly in the MS/S patient group, with declines of 3.6 points in the mild
      group, 3.5 points in the moderate group and 4.7 points in the MS/S group; between
      group differences did not reach statistical significance. Patients with MS/S AD
      dementia at baseline were more likely to be institutionalised (Kaplan-Meier
      probability 28% versus 9% in patients with mild AD dementia; p < 0.001 for
      difference across all severities) and had a greater probability of death (Kaplan
      Meier probability 15% versus 5%; p = 0.013) at 18 months. Greater disease
      severity at baseline was also associated with concomitant increases in caregiver
      time and mean total societal costs. Total societal costs of L43,560 over 18
      months were estimated for the MS/S group, versus L25,865 for the mild group and
      L30,905 for the moderate group (p < 0.001). Of these costs, over 50% were related
      to informal caregiver costs at each AD dementia severity level. CONCLUSIONS: This
      study demonstrated a mean deterioration in MMSE score over 18 months in patients
      with AD. It also showed that AD is a costly disease, with costs increasing with
      disease severity, even when managed in the community: informal caregiver costs
      represented the main contributor to societal costs.

PMID- 27887646
TI  - It's complicated: why do tuberculosis patients not initiate or stay adherent to
      treatment? A qualitative study from South Africa.
AB  - BACKGROUND: Individuals who test positive for active tuberculosis (TB) but do not
      initiate treatment present a challenge to TB programmes because they contribute
      to ongoing transmission within communities. To better understand why individuals
      do not initiate treatment, or are adherent after initiating treatment, South
      African respondents were approached to obtain insights as to which factors
      enabled and inhibited the treatment process. METHODS: This qualitative work was
      nested in a larger study investigating initial loss to follow-up (LTFU) amongst
      new smear positive TB patients across five provinces of South Africa. In-depth
      interviews were done with 41 adherent and initial LTFU respondents. RESULTS: Key
      issues contributing to initial LTFU appeared to be a poor knowledge, or low
      awareness of TB treatment; stigma around TB including its connection to HIV;
      immediate problems in the respondents' lives particularly poverty, lack of access
      to transport and the need to continue working; and problems in the healthcare
      facilities including under resourced facilities, poor functioning health systems
      and negative staff attitudes. In contrast the reasons given for being adherent
      related to the level of illness, support received at home and healthcare
      facilities, a belief in the health system and positive experiences in the health
      service including positive attitudes from staff. CONCLUSIONS: Key changes need to
      be made to the healthcare system to enable patients to initiate treatment and
      remain adherent, but the six month regimen of daily observed treatment presents
      real practical and personal challenges to patients. Alternative strategies to
      DOTS at facility level should be investigated to bring services closer to
      communities to encourage patients to access care, initiate and adhere to
      treatment.

PMID- 27887647
TI  - The hide and seek of Plasmodium vivax in West Africa: report from a large-scale
      study in Beninese asymptomatic subjects.
AB  - BACKGROUND: Plasmodium vivax is considered to be absent from western Africa,
      where the prevalence of Duffy-negative red blood cell phenotype proves to be
      high. Several studies have, however, detected P. vivax infection cases in this
      part of Africa, raising the question of what is the actual prevalence of P. vivax
      in local populations. METHODS: The presence of P. vivax was investigated in a
      large population of healthy blood donors in Benin using microscopy, serology and
      molecular detection. The seroprevalence was measured with species-specific ELISA
      using two recombinant P. vivax proteins, namely rPvMSP1 and rPvCSP1. Specific
      molecular diagnosis of P. vivax infection was carried out using nested-PCR. The
      performances and cut-off values of both rPvCSP1 and rPvMSP1 ELISA were first
      assessed using sera from P. vivax-infected patients and from non-exposed
      subjects. RESULTS: Among 1234 Beninese blood donors, no parasites were detected
      when using microscopy, whereas 28.7% (354/1234) of patients exhibited had
      antibodies against rPvMSP1, 21.6% (266/1234) against rPvCSP1, and 15.2%
      (187/1234) against both. Eighty-four samples were selected for nested-PCR
      analyses, of which 13 were positive for P. vivax nested-PCR and all Duffy
      negative. CONCLUSION: The results of the present study highlight an unexpectedly
      high exposure of Beninese subjects to P. vivax, resulting in sub-microscopic
      infections. This suggests a probably underestimated and insidious parasite
      presence in western Africa. While the vaccination campaigns and therapeutic
      efforts are all focused on Plasmodium falciparum, it is also essential to
      consider the epidemiological impact of P. vivax.

PMID- 27887648
TI  - The potential hazard of drug-eluting stent-induced coronary vasospasm causing
      subacute stent thrombosis: a case report.
AB  - BACKGROUND: Drug-eluting stent (DES) -induced coronary vasospasm is a well known
      phenomenon after stent implantation; however, the extent of this risk is still
      unknown. We report a case in which DES-induced severe coronary vasospasm was
      clinically suspected as a cause of subacute stent thrombosis (ST). CASE
      PRESENTATION: A 67-year-old man came to our hospital due to chest pain with mild
      exercise. He was diagnosed with effort angina by coronary angiography and
      underwent DES implantation in the mid-left ascending artery (LAD) after the
      administration of dual anti-platelet therapy. The procedure was uneventful, but
      his symptoms changed from effort angina to rest angina after stenting. Five days
      after the procedure, subacute ST occurred, requiring aspiration thrombectomy and
      balloon angioplasty. Thereafter, he continued to report early morning chest
      discomfort. We performed a spasm provocation test to evaluate the coronary
      vasomotor response; it revealed severe stent-edge spasm in the left main trunk to
      the LAD, except for the stented lesion, and total occlusion of the left
      circumflex artery. CONCLUSIONS: To our knowledge, the present case is the first
      report describing in-stent thrombosis secondary to stent-edge spasm. This case
      describes the potential hazard of DES-induced coronary vasospasm. Although there
      are several overlapping risk factors for ST development, we consider that stent
      edge spasm also plays an important role in ST development. Therefore, we should
      monitor new-onset rest angina after stent implantation and carefully assess DES
      induced coronary vasospasm.

PMID- 27887649
TI  - Postpartum depression in the Occupied Palestinian Territory: a longitudinal study
      in Bethlehem.
AB  - BACKGROUND: Postpartum depression (PPD) affects women from different cultures
      around the world. No previous studies have investigated PPD among women in
      Palestine. Fertility rates in Palestine are among the highest in the world, hence
      even low rates of PPD could have considerable national impact. The aim of this
      study was to determine the prevalence of, and risk factors for, PPD among
      Palestinian mothers. METHODS: 101 mothers were recruited during the registration
      of their child's birth (within 1 week) at the Bethlehem branch of the Ministry of
      Interior. Participants were assessed via a face to face interview, and were
      followed up 1 week, 2 weeks, 6 weeks, 3 months, and 6 months later by telephone
      interview. Interviews included the Arabic Edinburgh Postnatal Depression Scale
      (EPDS), with PPD indicated by depressive symptoms (EPDS score >=11) at >=2 follow
      up time points. Pearson's correlation was calculated between repeated EPDS
      scores, and multivariable logistic regression was used to investigate risk
      factors for PPD. RESULTS: The prevalence of depressive symptoms was fairly
      constant (14-19%) over the follow-up period. Most depressive symptoms developed
      within 1 month of delivery; mothers with depressive symptoms at 3 months
      postpartum were highly likely to still have symptoms at 6 months. 27.7% (28/101)
      of women met our criteria for PPD. High parity (odds ratio (OR) 4.52 (95% CI
      0.90, 22.8) parity 3+ versus primiparous), unplanned pregnancy (OR 2.44 (0.99,
      6.01)) and sex of child not being the one desired (OR 5.07 (1.12, 22.9)) were
      associated with PPD, but these associations were attenuated in multivariable
      analysis. CONCLUSIONS: The prevalence of PPD in Palestine appears to be higher
      than in high income countries, but similar to the prevalence in other Middle
      Eastern countries. High parity and unplanned pregnancy were identified as risk
      factors for PPD, suggesting that fully meeting the need for family planning could
      reduce the incidence of PPD in the Palestinian population.

PMID- 27887650
TI  - The anti-inflammatory effect of Andrographis paniculata (Burm. f.) Nees on pelvic
      inflammatory disease in rats through down-regulation of the NF-kappaB pathway.
AB  - BACKGROUND: Andrographis paniculata (Burm. f.) Nees (APN), a principal
      constituent of a famous traditional Chinese medicine Fukeqianjin tablet which is
      used for the treatment of pelvic inflammatory disease (PID), has been reported to
      have anti-inflammatory effect in vitro. However, whether it has pharmacological
      effect on PID in vivo is unclear. Therefore, the aim of this study is to test the
      anti-inflammatory effect of APN and illuminate a potential mechanism. METHODS:
      Thirty-six female specific pathogen-free SD rats were randomly divided into
      control group, PID group, APN1 group, APN2 group, APN3 group and prednisone
      group. Pathogen-induced PID rats were constructed. The APN1, APN2 and APN3 group
      rats were orally administrated with APN extract at different levels. The
      prednisone group rats were administrated with prednisone. Eight days after the
      first infection, the histological examination of upper genital tract was carried
      out, and enzyme-linked immunosorbent assay (ELISA) was carried out using
      homogenate of the uterus and fallopian tube. Furthermore, immunohistochemical
      evaluations of NF-kappaB p65 and IkappaB-alpha in uterus was conducted. RESULTS:
      APN obviously suppressed the infiltrations of neutrophils and lymphocytes, and it
      could significantly reduce the excessive production of cytokines and chemokines
      including IL-1beta, IL-6, CXCL-1, MCP-1 and RANTES in a dose-dependent manner.
      Furthermore, APN could block the pathogen-induced activation of NF-kappaB
      pathway. CONCLUSION: APN showed potent anti-inflammatory effect on pathogen
      induced PID in rats, with a potential mechanism of inhibiting the NF-kappaB
      signal pathway.

PMID- 27887651
TI  - Studies on the therapeutic effect of propolis along with standard antibacterial
      drug in Salmonella enterica serovar Typhimurium infected BALB/c mice.
AB  - BACKGROUND: Antibiotic resistance is an emerging public health problem. Centers
      for Disease Control and Prevention (CDC) has described antibiotic resistance as
      one of the world's most pressing health problems in 21st century. WHO rated
      antibiotic resistance as "one of the three greatest threats to human health". One
      important strategy employed to overcome this resistance is the use of combination
      of drugs. Many plants, natural extracts have been shown to exhibit synergistic
      response with standard drugs against microorganisms. The present study focused on
      the antibacterial potential of propolis in combination with the standard
      antibiotic Cefixime against the typhoid causing bacteria i.e. Salmonella.
      METHODS: Ethanolic extract of propolis was taken for the present work. For the
      experiment BALB/c mice were taken as animal model and divided into ten groups.
      Along with normal and infected control groups, four different combinations of
      cefixime and propolis were used. Biochemical, hematological and histopathological
      indices were studied by following the standard protocols. RESULTS: In BALB/c
      mice, Salmonella causes severe biochemical, hematological and histopathological
      alterations by 5th day of infection. Ethanolic extract of propolis at a dose of
      300 mg/kg body weight of mice when used alone to treat Salmonella infection in
      mice gave significant results by 30th day of treatment. Similarly, when cefixime
      (4 mg/kg body weight of mice) was used to treat infection in mice, significant
      results as compared to infected control were observed after 5th day. But when
      propolis and cefixime were used together in different concentrations in
      combination therapy, evident results were observed after 5 days of treatment. The
      levels of various liver and kidney function enzymes, blood indices and the
      histopathology of liver, spleen and kidney were restored to near normal after 5
      days of treatment and at much lower doses as compared to the effective dose when
      used alone. CONCLUSION: The study confirmed that significant results were
      observed in three combinations of cefixime and propolis as compared to infected
      controls. Propolis acted synergistically with cefixime and enhanced the efficacy
      of antibiotic and reduced its effective dose in combined therapy.

PMID- 27887652
TI  - Limitations of malaria reactive case detection in an area of low and unstable
      transmission on the Myanmar-Thailand border.
AB  - BACKGROUND: Reactive case detection is an approach that has been proposed as a
      tool for malaria elimination in low-transmission settings. It is an intuitively
      justified approach based on the concept of space-time clustering of malaria
      cases. When an index malaria clinical case is detected, it triggers reactive
      screening and treatment in the index house and neighbouring houses. However, the
      efficacy of this approach at varying screening radii and malaria prevalence
      remains ill defined. METHODS: Data were obtained from a detailed demographic and
      geographic surveillance study in four villages on the Myanmar-Thailand border.
      Clinical cases were recorded at village malaria clinics and were linked back to
      patients' residencies. These data were used to simulate the efficacy of reactive
      case detection for clinical cases using rapid diagnostic tests (RDT). Simulations
      took clinical cases in a given month and tabulated the number of cases that would
      have been detected in the following month at varying screening radii around the
      index houses. Simulations were run independently for both falciparum and vivax
      malaria. Each simulation of a reactive case detection effort was run in
      comparison with a strategy using random selection of houses for screening.
      RESULTS: In approximately half of the screenings for falciparum and 10% for vivax
      it would have been impossible to detect any malaria cases regardless of the
      screening strategy because the screening would have occurred during times when
      there were no cases. When geographically linked cases were present in the
      simulation, reactive case detection would have only been successful at detecting
      most malaria cases using larger screening radii (150-m radius and above). At this
      screening radius and above, reactive case detection does not perform better than
      random screening of an equal number of houses in the village. Screening within
      very small radii detects only a very small proportion of cases, but despite this
      low performance is better than random screening with the same sample size.
      CONCLUSIONS: The results of these simulations indicate that reactive case
      detection for clinical cases using RDTs has limited ability in halting
      transmission in regions of low and unstable transmission. This is linked to high
      spatial heterogeneity of cases, acquisition of malaria infections outside the
      village, as well missing asymptomatic infections. When cases are few and
      sporadic, reactive case detection would result in major time and budgetary
      losses.

PMID- 27887653
TI  - Intravascular versus surface cooling for targeted temperature management after
      out-of-hospital cardiac arrest - an analysis of the TTM trial data.
AB  - BACKGROUND: Targeted temperature management is recommended after out-of-hospital
      cardiac arrest and may be achieved using a variety of cooling devices. This study
      was conducted to explore the performance and outcomes for intravascular versus
      surface devices for targeted temperature management after out-of-hospital cardiac
      arrest. METHOD: A retrospective analysis of data from the Targeted Temperature
      Management trial. N = 934. A total of 240 patients (26%) managed with
      intravascular versus 694 (74%) with surface devices. Devices were assessed for
      speed and precision during the induction, maintenance and rewarming phases in
      addition to adverse events. All-cause mortality, as well as a composite of poor
      neurological function or death, as evaluated by the Cerebral Performance Category
      and modified Rankin scale were analysed. RESULTS: For patients managed at 33 
      degrees C there was no difference between intravascular and surface groups in the
      median time taken to achieve target temperature (210 [interquartile range (IQR)
      180] minutes vs. 240 [IQR 180] minutes, p = 0.58), maximum rate of cooling (1.0
      [0.7] vs. 1.0 [0.9]  degrees C/hr, p = 0.44), the number of patients who reached
      target temperature (within 4 hours (65% vs. 60%, p = 0.30); or ever (100% vs.
      97%, p = 0.47), or episodes of overcooling (8% vs. 34%, p = 0.15). In the
      maintenance phase, cumulative temperature deviation (median 3.2 [IQR 5.0] 
      degrees C hr vs. 9.3 [IQR 8.0]  degrees C hr, p = <0.001), number of patients
      ever out of range (57.0% vs. 91.5%, p = 0.006) and median time out of range (1
      [IQR 4.0] hours vs. 8.0 [IQR 9.0] hours, p = <0.001) were all significantly
      greater in the surface group although there was no difference in the occurrence
      of pyrexia. Adverse events were not different between intravascular and surface
      groups. There was no statistically significant difference in mortality
      (intravascular 46.3% vs. surface 50.0%; p = 0.32), Cerebral Performance Category
      scale 3-5 (49.0% vs. 54.3%; p = 0.18) or modified Rankin scale 4-6 (49.0% vs.
      53.0%; p = 0.48). CONCLUSIONS: Intravascular and surface cooling was equally
      effective during induction of mild hypothermia. However, surface cooling was
      associated with less precision during the maintenance phase. There was no
      difference in adverse events, mortality or poor neurological outcomes between
      patients treated with intravascular and surface cooling devices. TRIAL
      REGISTRATION: TTM trial ClinicalTrials.gov number
      https://clinicaltrials.gov/ct2/show/NCT01020916 NCT01020916; 25 November 2009.

PMID- 27887654
TI  - Proportion of children meeting recommendations for 24-hour movement guidelines
      and associations with adiposity in a 12-country study.
AB  - BACKGROUND: The Canadian 24-h movement guidelines were developed with the hope of
      improving health and future health outcomes in children and youth. The purpose of
      this study was to evaluate adherence to the 3 recommendations most strongly
      associated with health outcomes in new 24-h movement guidelines and their
      relationship with adiposity (obesity and body mass index z-score) across
      countries participating in the International Study of Childhood Obesity,
      Lifestyle and the Environment (ISCOLE). METHODS: Cross-sectional results were
      based on 6128 children aged 9-11 years from the 12 countries of ISCOLE. Sleep
      duration and moderate-to-vigorous physical activity (MVPA) were assessed using
      accelerometry. Screen time was measured through self-report. Body weight and
      height were measured. Body mass index (BMI, kg . m-2) was calculated, and BMI z
      scores were computed using age- and sex-specific reference data from the World
      Health Organization. Obesity was defined as a BMI z-score > +2 SD. Meeting the
      overall 24-h movement guidelines was defined as: 9 to 11 h/night of sleep, <=2
      h/day of screen time, and at least 60 min/day of MVPA. Age, sex, highest parental
      education and unhealthy diet pattern score were included as covariates in
      statistical models. Associations between meeting vs. not meeting each single
      recommendation (and combinations) with obesity were assessed with odds ratios
      calculated using generalized linear mixed models. A linear mixed model was used
      to examine the differences in BMI z-scores between children meeting vs. not
      meeting the different combinations of recommendations. RESULTS: The global
      prevalence of children meeting the overall recommendations (all three behaviors)
      was 7%, with children from Australia and Canada showing the highest adherence
      (15%). Children meeting the three recommendations had lower odds ratios for
      obesity compared to those meeting none of the recommendations (OR = 0.28, 95% CI
      0.18-0.45). Compared to not meeting the 24-h movement recommendations either
      independently or combined, meeting them was significantly associated with a lower
      BMI z-score. Whenever the MVPA recommendation was included in the analysis the
      odds ratios for obesity were lower. CONCLUSIONS: For ISCOLE participants meeting
      these 3 healthy movement recommendations the odds ratios of being obese or having
      high BMI z-scores were lower. However, only a small percentage of children met
      all recommendations. Future efforts should aim to find promising ways to increase
      daily physical activity, reduce screen time, and ensure an adequate night's sleep
      in children. TRIAL REGISTRATION: The International Study of Childhood Obesity,
      Lifestyle and the Environment (ISCOLE) was registered at ClinicalTrials.gov
      (Identifier NCT01722500) (October 29, 2012).

PMID- 27887655
TI  - Fracture risk and healthcare resource utilization and costs among osteoporosis
      patients with type 2 diabetes mellitus and without diabetes mellitus in Japan:
      retrospective analysis of a hospital claims database.
AB  - BACKGROUND: Osteoporosis, osteoporosis-related fractures, and diabetes are
      considerable health burdens in Japan. Diabetes in patients with osteoporosis has
      been reported to be associated with increased fracture risk. This retrospective
      analysis of a Japanese hospital claims database investigated the real-world
      effect of type 2 diabetes mellitus (T2DM) on the incidence of clinical fractures,
      costs, and healthcare resource utilization in patients with osteoporosis and a
      subgroup of patients prescribed raloxifene. METHODS: Women aged >=50 years
      diagnosed with osteoporosis who had a first prescription claim for osteoporosis
      treatment with a pre-index period >=12 months and a post-index period of 30
      months were selected from a database extract (April 2008-July 2013). Patients
      prescribed raloxifene were classed as a subgroup. Patients diagnosed with T2DM
      constituted the T2DM group; all other patients (excluding patients with type 1
      diabetes mellitus) constituted the non-diabetes mellitus (non-DM) group. Groups
      were matched by exact matching, using selected baseline characteristics. Patient
      demographic and clinical characteristics were compared using chi-squared tests, t
      tests, or Wilcoxon rank sum tests. Time to first fracture was examined using
      Kaplan-Meier survival analysis. RESULTS: Overall, the T2DM and non-DM groups had
      7580 and 7979 patients, respectively; following matching, there were 3273
      patients per group. In the raloxifene subgroup, the T2DM and non-DM groups had
      668 and 699 patients, respectively; following matching, there were 239 patients
      per group. At baseline, the T2DM group (overall and raloxifene subgroup) had
      significantly higher healthcare resource utilization and comorbidities. During
      the post-index period, a similar pattern was observed in the overall group, even
      after matching; the T2DM group also had a higher incidence of fracture. In the
      raloxifene subgroup, after matching, there were no significant differences in
      fracture incidence or costs and fewer differences in healthcare resource
      utilization between the T2DM and non-DM groups. CONCLUSIONS: These findings
      suggest that comorbid T2DM increases fracture incidence in patients with
      osteoporosis, compared with patients without DM. Increases in fracture incidence
      were accompanied by greater costs and healthcare resource utilization, which are
      important considerations for clinical practice in Japan. Further research
      investigating the use of raloxifene for treatment of osteoporosis with comorbid
      T2DM may also be warranted.

PMID- 27887656
TI  - Looking beyond the cancer cell for effective drug combinations.
AB  - Combinations of therapies are being actively pursued to expand therapeutic
      options and deal with cancer's pervasive resistance to treatment. Research
      efforts to discover effective combination treatments have focused on drugs
      targeting intracellular processes of the cancer cells and in particular on small
      molecules that target aberrant kinases. Accordingly, most of the computational
      methods used to study, predict, and develop drug combinations concentrate on
      these modes of action and signaling processes within the cancer cell. This focus
      on the cancer cell overlooks significant opportunities to tackle other components
      of tumor biology that may offer greater potential for improving patient survival.
      Many alternative strategies have been developed to combat cancer; for example,
      targeting different cancer cellular processes such as epigenetic control;
      modulating stromal cells that interact with the tumor; strengthening physical
      barriers that confine tumor growth; boosting the immune system to attack tumor
      cells; and even regulating the microbiome to support antitumor responses. We
      suggest that to fully exploit these treatment modalities using effective drug
      combinations it is necessary to develop multiscale computational approaches that
      take into account the full complexity underlying the biology of a tumor, its
      microenvironment, and a patient's response to the drugs. In this Opinion article,
      we discuss preliminary work in this area and the needs-in terms of both
      computational and data requirements-that will truly empower such combinations.

PMID- 27887657
TI  - Complexity galore: 3D cultures, biomechanics and systems medicine at the eighth
      ENBDC workshop "Methods in Mammary Gland Development and Cancer".
AB  - The ENBDC workshop "Methods in Mammary Gland Development and Cancer" is an
      established international forum to showcase the latest technical advances in the
      field. The eighth meeting focused on emerging concepts and technologies for
      studying normal and neoplastic breast development.

PMID- 27887658
TI  - Parameter set for computer-assisted texture analysis of fetal brain.
AB  - BACKGROUND: Magnetic resonance data were collected from a diverse population of
      gravid women to objectively compare the quality of 1.5-tesla (1.5 T) versus 3-T
      magnetic resonance imaging of the developing human brain. MaZda and B11
      computational-visual cognition tools were used to process 2D images. We proposed
      a wavelet-based parameter and two novel histogram-based parameters for Fisher
      texture analysis in three-dimensional space. RESULTS: Wavenhl, focus index, and
      dispersion index revealed better quality for 3 T. Though both 1.5 and 3 T images
      were 16-bit DICOM encoded, nearly 16 and 12 usable bits were measured in 3 and
      1.5 T images, respectively. The four-bit padding observed in 1.5 T K-space
      encoding mimics noise by adding illusionistic details, which are not really part
      of the image. In contrast, zero-bit padding in 3 T provides space for storing
      more details and increases the likelihood of noise but as well as edges, which in
      turn are very crucial for differentiation of closely related anatomical
      structures. CONCLUSIONS: Both encoding modes are possible with both units, but
      higher 3 T resolution is the main difference. It contributes to higher perceived
      and available dynamic range. Apart from surprisingly larger Fisher coefficient,
      no significant difference was observed when testing was conducted with down
      converted 8-bit BMP images.

PMID- 27887659
TI  - Fab glycosylation of immunoglobulin G does not associate with improvement of
      rheumatoid arthritis during pregnancy.
AB  - BACKGROUND: Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation
      are associated with changes in rheumatoid arthritis (RA) disease activity in
      response to pregnancy. Here, we sought to determine whether the same holds true
      for variable domain (Fab) glycosylation. METHODS: IgGs were captured from RA and
      control sera obtained before (RA only), during and after pregnancy, followed by
      Fc and Fab separation, glycan release, and mass spectrometric detection. In
      parallel, glycans from intact IgG were analysed. The data was used to calculate
      glycosylation traits, and to estimate the level of Fab glycosylation. RESULTS:
      The overall level of Fab glycosylation was increased in RA patients compared to
      controls, while no differences in Fab glycosylation patterns were found. For the
      Fc and intact IgG (Total) previously observed differences in galactosylation and
      bisection were confirmed. Furthermore, increased galactosylation of Fc and Total
      were associated with lower disease activity and autoantibody positivity. In
      addition, the change in Fc galactosylation associated with the change in disease
      activity during pregnancy and after delivery, while this was not the case for
      Fab. CONCLUSIONS: In contrast to changes in Fc glycosylation, changes in Fab
      glycosylation are not associated with improvement of RA during pregnancy and
      arthritis flare after delivery.

PMID- 27887661
TI  - Biochemical and proteomic analyses of the physiological response induced by
      individual housing in gilts provide new potential stress markers.
AB  - BACKGROUND: The objective assessment of animal stress and welfare requires proper
      laboratory biomarkers. In this work, we have analyzed the changes in serum
      composition in gilts after switching their housing, from pen to individual
      stalls, which is generally accepted to cause animal discomfort. RESULTS: Blood
      and saliva samples were collected a day before and up to four days after changing
      the housing system. Biochemical analyses showed adaptive changes in lipid and
      protein metabolism after the housing switch, whereas cortisol and muscular
      markers showed a large variability between animals. 2D-DIGE and iTRAQ proteomic
      approaches revealed variations in serum protein composition after changing
      housing and diet of gilts. Both techniques showed alterations in two main
      homeostatic mechanisms: the innate immune and redox systems. The acute phase
      proteins haptoglobin, apolipoprotein A-I and alpha1-antichymotrypsin 3, and the
      antioxidant enzyme peroxiredoxin 2 were found differentially expressed by 2D
      DIGE. Other proteins related to the innate immune system, including
      lactotransferrin, protegrin 3 and galectin 1 were also identified by iTRAQ, as
      well as oxidative stress enzymes such as peroxiredoxin 2 and glutathione
      peroxidase 3. Proteomics also revealed the decrease of apolipoproteins, and the
      presence of intracellular proteins in serum, which may indicate physical injury
      to tissues. CONCLUSIONS: Housing of gilts in individual stalls and diet change
      increase lipid and protein catabolism, oxidative stress, activate the innate
      immune system and cause a certain degree of tissue damage. We propose that
      valuable assays for stress assessment in gilts may be based on a score composed
      by a combination of salivary cortisol, lipid metabolites, innate immunity and
      oxidative stress markers and intracellular proteins.

PMID- 27887660
TI  - Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem
      cells achieved full donor engraftment in refractory acute lymphoblastic leukemia.
AB  - BACKGROUND: Elderly patients with relapsed and refractory acute lymphoblastic
      leukemia (ALL) have poor prognosis. Autologous CD19 chimeric antigen receptor
      modified T (CAR-T) cells have potentials to cure patients with B cell ALL;
      however, safety and efficacy of allogeneic CD19 CAR-T cells are still
      undetermined. CASE PRESENTATION: We treated a 71-year-old female with relapsed
      and refractory ALL who received co-infusion of haplo-identical donor-derived CD19
      directed CAR-T cells and mobilized peripheral blood stem cells (PBSC) following
      induction chemotherapy. Undetectable minimal residual disease by flow cytometry
      was achieved, and full donor cell engraftment was established. The transient
      release of cytokines and mild fever were detected. Significantly elevated serum
      lactate dehydrogenase, alanine transaminase, bilirubin and glutamic-oxalacetic
      transaminase were observed from days 14 to 18, all of which were reversible after
      immunosuppressive therapy. CONCLUSIONS: Our preliminary results suggest that co
      infusion of haplo-identical donor-derived CAR-T cells and mobilized PBSCs may
      induce full donor engraftment in relapsed and refractory ALL including elderly
      patients, but complications related to donor cell infusions should still be
      cautioned. TRIAL REGISTRATION: Allogeneic CART-19 for Elderly Relapsed/Refractory
      CD19+ ALL. NCT02799550.

PMID- 27887662
TI  - The effects of water lubrication of tracheal tubes on post-intubation airway
      complications: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Water is known to have lubricating properties, thus it is used for
      lubrication of tracheal tubes to reduce airway injuries caused by intubation.
      However, there is no definite evidence to substantiate the beneficial effects of
      lubricating tracheal tubes using water for attenuating airway injuries. Moreover,
      the lubrication pretreatment may cause contamination of the tube, leading to
      respiratory infections. Therefore, this trial aims to assess whether no
      pretreatment of tracheal tubes does not increase post-intubation airway
      complications as compared with water lubrication of tubes. METHODS/DESIGN: This
      is a prospective, double-blind, single-center, parallel-arm, noninferiority,
      randomized controlled trial to be conducted in participants aged 20-80 years who
      are undergoing elective surgery under general anesthesia with orotracheal
      intubation. Participants are randomly assigned into one of two groups depending
      on whether intubation is performed using a tracheal tube lubricated with water (n
      = 150) or without any pretreatment (n = 150). The primary outcome is the
      incidence of sore throat at 0, 2, 4, and 24 h after surgery, which is analyzed
      with a noninferiority test. The secondary outcomes are the incidence and severity
      of postoperative hoarseness, oropharyngeal injuries, and respiratory infections.
      DISCUSSION: Because we hypothesized that lubricating tracheal tubes using water
      has no advantage in reducing airway injuries associated with intubation, we will
      compare the incidence of sore throat, which is the most common complaint after
      intubation, in a noninferiority manner. This is the first randomized controlled
      trial to investigate the possibly beneficial or harmful effects of lubricating
      tracheal tubes using water before intubation. We expect that this trial will
      provide useful evidence to formulate a protocol for preparing tracheal tubes
      before intubation. TRIAL REGISTRATION: This trial is registered at
      ClinicalTrials.gov on 1 July 2015 ( NCT02492646 ).

PMID- 27887663
TI  - Effects of royal jelly supplementation on regulatory T cells in children with
      SLE.
AB  - BACKGROUND AND OBJECTIVE: To our knowledge, no previous studies have focused on
      the immunomodulatory effects of fresh royal jelly (RJ) administration on systemic
      lupus erythematosus (SLE) in humans. Our aim was to study the effect of fresh RJ
      administration on the disease course in children with SLE with some immunological
      markers (CD4+ and CD8+ regulatory T cells and T lymphocytes apoptosis). METHODS:
      This was an open-label study in which 20 SLE children received 2 g of freshly
      prepared RJ daily, for 12 weeks. RESULTS: The percentages of CD4+ CD25+high
      FOXP3+cells (CD4+ regulatory T cells) and CD8+CD25+high FOXP3+cells (CD8+
      regulatory T cells) were significantly increased after RJ treatment when compared
      with baseline values. Apoptotic CD4 T lymphocytes were significantly decreased
      after RJ therapy when compared with baseline values and the control group.
      CONCLUSION: This is the first human study on the effect of RJ supplementation in
      children with SLE. Our results showed improvements with 3-month RJ treatment with
      regard to the clinical severity score and laboratory markers for the disease. At
      this stage, it is a single study with a small number of patients, and a great
      deal of additional wide-scale randomized controlled studies are needed to
      critically validate the efficacy of RJ in SLE.

PMID- 27887664
TI  - Translating sickle cell guidelines into practice for primary care providers with
      Project ECHO.
AB  - BACKGROUND: Approximately 100,000 persons with sickle cell disease (SCD) live in
      the United States, including 15,000 in the Midwest. Unfortunately, many patients
      experience poor health outcomes due to limited access to primary care providers
      (PCPs) who are prepared to deliver evidence-based SCD care. Sickle Treatment and
      Outcomes Research in the Midwest (STORM) is a regional network established to
      improve care and outcomes for individuals with SCD living in Indiana, Illinois,
      Michigan, Minnesota, Ohio, and Wisconsin. METHODS: STORM investigators
      hypothesized that Project ECHO(r) methodology could be replicated to create a low
      cost, high-impact intervention to train PCPs in evidence-based care for pediatric
      and young adult patients with SCD in the Midwest, called STORM TeleECHO. This
      approach utilizes video technology for monthly telementoring clinics consisting
      of didactic and case-based presentations focused on the National Heart, Lung and
      Blood Institute (NHLBI) evidence-based guidelines for SCD. RESULTS: Network leads
      in each of the STORM states assisted with developing the curriculum and are
      recruiting providers for monthly clinics. To assess STORM TeleECHO feasibility
      and acceptability, monthly attendance and satisfaction data are collected.
      Changes in self-reported knowledge, comfort, and practice patterns will be
      compared with pre-participation, and 6 and 12 months after participation.
      CONCLUSIONS: STORM TeleECHO has the potential to increase implementation of the
      NHLBI evidence-based guidelines, especially increased use of hydroxyurea,
      resulting in improvements in the quality of care and outcomes for children and
      young adults with SCD. This model could be replicated in other pediatric chronic
      illness conditions to improve PCP knowledge and confidence in delivering evidence
      based care.

PMID- 27887665
TI  - In the eye of the beholder: to make global health estimates useful, make them
      more socially robust.
AB  - A plethora of new development goals and funding institutions have greatly
      increased the demand for internationally comparable health estimates in recent
      years and have brought important new players into the field of health estimate
      production. These changes have rekindled debates about the validity and
      legitimacy of global health estimates. This paper draws on country case studies
      and personal experience to support our opinion that the production and use of
      estimates are deeply embedded in specific social, economic, political, and
      ideational contexts, which vary at different levels of the global health
      architecture. Broadly, most global health estimates tend to be made far from the
      localities where the data upon which they are based are collected and where the
      results of estimation processes must ultimately be used if they are to make a
      difference to the health of individuals. Internationally standardised indicators
      are necessary, but they are no substitute for data that meet local needs and that
      fit with local ideas of what is credible and useful - in other words, data that
      are both technically and socially robust for those who make key decisions about
      health. We suggest that greater engagement of local actors (and local data) in
      the formulation, communication, and interpretation of health estimates would
      increase the likelihood that these data will be used by those most able to
      translate them into health gains for the longer term. Besides strengthening
      national information systems, this requires ongoing interaction, building trust,
      and establishing a communicative infrastructure. Local capacities to use
      knowledge to improve health must be supported.

PMID- 27887666
TI  - Contributions of national and global health estimates to monitoring health
      related sustainable development goals.
AB  - The millennium development goals triggered an increased demand for data on child
      and maternal mortalities for monitoring progress. With the advent of the
      sustainable development goals and growing evidence of an epidemiological
      transition toward non-communicable diseases, policymakers need data on mortality
      and disease trends and distribution to inform effective policies and support
      monitoring progress. Where there are limited capacities to produce national
      health estimates (NHEs), global health estimates (GHEs) can fill gaps for global
      monitoring and comparisons. This paper discusses lessons learned from Thailand's
      burden of disease (BOD) study on capacity development on NHEs and discusses the
      contributions and limitations of GHEs in informing policies at the country level.
      Through training and technical support by external partners, capacities are
      gradually strengthened and institutionalized to enable regular updates of BOD at
      national and subnational levels. Initially, the quality of cause-of-death
      reporting in death certificates was inadequate, especially for deaths occurring
      in the community. Verbal autopsies were conducted, using domestic resources, to
      determine probable causes of deaths occurring in the community. This method
      helped to improve the estimation of years of life lost. Since the achievement of
      universal health coverage in 2002, the quality of clinical data on morbidities
      has also considerably improved. There are significant discrepancies between the
      Global Burden of Disease 2010 study estimates for Thailand and the 1999
      nationally generated BOD, especially for years of life lost due to HIV/AIDS, and
      the ranking of priority diseases. National ownership of NHEs and an effective
      interface between researchers and decision-makers contribute to enhanced country
      policy responses, whereas subnational data are intended to be used by various
      subnational partners. Although GHEs contribute to benchmarking country
      achievement compared with global health commitments, they may hamper development
      of NHE capacities. GHEs should encourage and support countries to improve their
      data systems and develop a data infrastructure that supports the production of
      empirical data needed to underpin estimation efforts.

PMID- 27887667
TI  - From instinct to evidence: the role of data in country decision-making in Chile.
AB  - BACKGROUND: The Chilean health system has undergone profound reforms since 1990,
      while going through many political upheavals, and faced demographic, health, and
      economic transformations. The full information requirements to develop an
      evidence-informed process implied the best possible use of available data, as
      well as efforts for improving the information systems. OBJECTIVE: To examine,
      from a historical perspective, the use of data during the health reforms
      undertaken in Chile since 1990, and to identify the factors that have determined
      its utilization and improvement. DESIGN: A qualitative methodological approach
      was followed to review the case study of the Chilean experience with data on
      decision-making. We use as the primary source our first-hand experience as
      officials of the Ministry of Health (MOH) and the Ministry of Finance during the
      reform period considered. Second, a literature review was conducted, using
      documents from official sources, historical accounts, books, policy reports, and
      articles about the reform process, looking for the use of data. FINDINGS: The
      Chilean health care reform process was intensive in utilization and production of
      information. In this context, the MOH conducted several studies, from the burden
      of disease, efficacy of interventions, cost-effectiveness, out-of-pocket
      payments, and fiscal impact to social preferences, among others. Policy and
      prioritization frameworks developed by international agencies influenced the use
      of data and the studies' agenda. CONCLUSIONS: Health systems in Latin America
      have struggled to adapt to changing health needs caused by demographic transition
      and economic growth. Health reforms in Chile provide lessons of this sustained
      effort, based on data and scientific grounds, with lights and shadows. Tradition,
      receptiveness to foreign ideas, and benchmarking with international data
      determined this approach, facilitated by the political influence of physicians
      and other technocrats. Besides, internationally comparable statistics are shown
      to play a significant role in policy debate.

PMID- 27887668
TI  - Meddling with middle modalities: a decomposition approach to mental health
      inequalities between intersectional gender and economic middle groups in northern
      Sweden.
AB  - BACKGROUND: Intersectionality has received increased interest within population
      health research in recent years, as a concept and framework to understand
      entangled dimensions of health inequalities, such as gender and socioeconomic
      inequalities in health. However, little attention has been paid to the
      intersectional middle groups, referring to those occupying positions of mixed
      advantage and disadvantage. OBJECTIVE: This article aimed to 1) examine mental
      health inequalities between intersectional groups reflecting structural positions
      of gender and economic affluence and 2) decompose any observed health
      inequalities, among middle groups, into contributions from experiences and
      conditions representing processes of privilege and oppression. DESIGN:
      Participants (N=25,585) came from the cross-sectional 'Health on Equal Terms'
      survey covering 16- to 84-year-olds in the four northernmost counties of Sweden.
      Six intersectional positions were constructed from gender (woman vs. men) and
      tertiles (low vs. medium vs. high) of disposable income. Mental health was
      measured through the General Health Questionnaire-12. Explanatory variables
      covered areas of material conditions, job relations, violence, domestic burden,
      and healthcare contacts. Analysis of variance (Aim 1) and Blinder-Oaxaca
      decomposition analysis (Aim 2) were used. RESULTS: Significant mental health
      inequalities were found between dominant (high-income women and middle-income
      men) and subordinate (middle-income women and low-income men) middle groups. The
      health inequalities between adjacent middle groups were mostly explained by
      violence (mid-income women vs. men comparison); material conditions (mid- vs. low
      income men comparison); and material needs, job relations, and unmet medical
      needs (high- vs. mid-income women comparison). CONCLUSIONS: The study suggests
      complex processes whereby dominant middle groups in the intersectional space of
      economic affluence and gender can leverage strategic resources to gain mental
      health advantage relative to subordinate middle groups.

PMID- 27887669
TI  - Couple interdependence impacts HIV-related health behaviours among pregnant
      couples in southwestern Kenya: a qualitative analysis.
AB  - INTRODUCTION: HIV infection is frequently transmitted within stable couple
      partnerships. In order to prevent HIV acquisition in HIV-negative couples, as
      well as improve coping in couples with an HIV-positive diagnosis, it has been
      suggested that interventions be aimed at strengthening couple relationships, in
      addition to addressing individual behaviours. However, little is known about
      factors that influence relationships to impact joint decision-making related to
      HIV. METHODS: We conducted qualitative in-depth interviews with 40 pregnant women
      and 40 male partners in southwestern Kenya, an area of high HIV prevalence.
      Drawing from the interdependence model of communal coping and health behaviour
      change, we employed thematic analysis methods to analyze interview transcripts in
      Dedoose software with the aim of identifying key relationship factors that could
      contribute to the development of a couples-based intervention to improve health
      outcomes for pregnant women and their male partners. RESULTS: In accordance with
      the interdependence model, we found that couples with greater relationship
      centred motivations described jointly engaging in more health-enhancing
      behaviours, such as couples HIV testing, disclosure of HIV status, and
      cooperation to improve medication and clinic appointment adherence. These couples
      often had predisposing factors such as stronger communication skills and shared
      children, and were less likely to face potential challenges such as polygamous
      marriages, wife inheritance, living separately, or financial difficulties. For
      HIV-negative couples, joint decision-making helped them face the health threat of
      acquiring HIV together. For couples with an HIV-positive diagnosis, communal
      coping helped reduce risk of interspousal transmission and improve long-term
      health prospects. Conversely, participants felt that self-centred motivations led
      to more concurrent sexual partnerships, reduced relationship satisfaction, and
      mistrust. Couples who lacked interdependence were more likely to mention
      experiencing violence or relationship dissolution, or having difficulty coping
      with HIV-related stigma. CONCLUSIONS: We found that interdependence theory may
      provide key insights into health-related attitudes and behaviours adopted by
      pregnant couples. Interventions that invest in strengthening relationships, such
      as couple counselling during pregnancy, may improve adoption of beneficial HIV
      related health behaviours. Future research should explore adaptation of existing
      evidence-based couple counselling interventions to local contexts, in order to
      address modifiable relationship characteristics that can increase interdependence
      and improve HIV-related health outcomes.

PMID- 27887670
TI  - Early progression under mitotane and polychemotherapy does not mean failure in
      adrenocortical carcinoma patient.

PMID- 27887671
TI  - Choroidal metastasis from papillary thyroid cancer: An unusual feature of a
      common disease.

PMID- 27887672
TI  - Cost of Cutaneous Melanoma by Tumor Stage: A Descriptive Analysis.
AB  - BACKGROUND AND OBJECTIVE: The basis for optimal resource allocation is an
      understanding of requirements during the diagnostic and treatment phases. Costs
      associated with the rising incidence of cutaneous melanoma are considerable. We
      undertook an up-to-date analysis of the cost of diagnosis, treatment, and follow
      up according to tumor stage. METHODS: We constructed descriptive tables following
      a theoretical model of direct costs based on amounts published in directives for
      the Spanish national health system and in international guidelines for managing
      cutaneous melanoma according to stage at diagnosis and clinical course. The
      tables allowed us to calculate the cost of treating individual patients as well
      as the expected cost for all patients with tumors in the same stage. RESULTS:
      Individual patients would generate costs ranging from ?1689 (for a stage I tumor)
      to ?88, 268 (stage IV). The largest differences were between stages IA and IB-IIA
      and between stages III and IV. Costs differed greatly between patients with early
      stage tumors and favorable outcomes and those with recurring tumors, which cost
      50-fold more in the first year and 20-fold more after 10 years of follow-up.
      CONCLUSIONS: The high cost of diagnosing advanced-stage cutaneous melanoma calls
      attention to the need to promote primary prevention and early detection. Our
      findings provide the knowledge base for cost-effectiveness studies in this
      disease.

PMID- 27887673
TI  - A reddish plaque in the forehead.

PMID- 27887674
TI  - Nodule on the External Ear.

PMID- 27887675
TI  - Clinical Efficacy and Safety of Ixekizumab for Treatment of Psoriasis.
AB  - Psoriasis is a common, chronic, inflammatory skin disorder with a physical and
      emotional burden. Emerging evidence suggests that IL17-A is a key cytokine in the
      immunopathogenesis of psoriasis. Ixekizumab is a humanized IgG4 monoclonal
      antibody that acts by neutralizing IL-17A. Data from Phase I-III studies reveal
      that ixekizumab is highly effective in treating patients with moderate-to-severe
      plaque psoriasis. A large proportion of patients receiving ixekizumab achieved or
      maintained complete or near complete resolution of psoriatic lesions with an
      acceptable safety profile through week 60. These remarkable results introduce a
      paradigm shift in the medically management of psoriasis, where complete or almost
      completely clear skin becomes the new therapeutic goal.

PMID- 27887676
TI  - Trauma patients: I can't get no (patient) satisfaction?
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) provides
      financial incentives to hospitals based on the Hospital Consumer Assessment of
      Healthcare Providers and Systems (HCAHPS) patient satisfaction survey. This data
      is made publicly available on their website to be utilized by patients and
      insurers. Hospitals are profoundly interested in identifying patient populations
      that negatively contribute to overall patient satisfaction scores. Hospitals
      consider trauma patients "high risk" from a HCAHPS perspective, but there is no
      data to inform this opinion. The purpose of this study is to evaluate trauma
      patient satisfaction scores and their impact on overall patient satisfaction.
      METHODS: Three different analyses were performed. Group 1 was composed of ALL
      patients admitted to our hospital over a 7-month period who were administered a
      validated patient satisfaction survey by a 3rd party and compared patient
      satisfaction of trauma vs. non-trauma patients (ALL). Group 2 compared admitted
      patients with a specific ICD-9 procedure code to non-trauma patients who
      underwent a procedure with the same ICD-9 code (ICD). Group 3 examines patient
      satisfaction between three Level I Trauma Centers within our geographic area
      (TC). Patient satisfaction data of trauma vs non-trauma patients (ALL), those
      with a specific ICD-9 procedure code (ICD), and the 3 Level I Trauma Centers in
      our area (TC) were analyzed with the appropriate statistical test. RESULTS: In
      the ALL group, no difference in satisfaction was noted in 18/21 questions for
      trauma patients when compared to non-trauma patients at our hospital. In the ICD
      group, 57 ICD-9 procedure codes were analyzed. Of these, only patients who
      required spinal fusion secondary to trauma reported lower overall patient
      satisfaction. No meaningful difference was found in HCAHPS associated
      satisfaction between the Level I Trauma Centers in our area (TC). CONCLUSION: In
      contrast to commonly held opinion, trauma patients do not negatively contribute
      to overall patient satisfaction in our facility. Certain injuries may offer
      opportunities for improvement and efforts around improved physician-patient
      communication may be warranted. In the era of public reporting and financial
      penalties, surgeons should embrace patient satisfaction as it may be vital to the
      survival of the trauma center.

PMID- 27887677
TI  - Outcome disparities between African Americans and Caucasians in contemporary
      kidney transplant recipients.
AB  - BACKGROUND: Racial disparities in African-American (AA) kidney transplant have
      persisted for nearly 40 years, with limited data available on the scope of this
      issue in the contemporary era of transplantation. METHODS: Descriptive
      retrospective cohort study of US registry data including adult solitary kidney
      transplants between Jan 1, 2005 to Dec 31, 2009. RESULTS: 60,695 recipients were
      included; 41,426 Caucasians (68%) and 19,269 AAs (32%). At baseline, AAs were
      younger, had lower college graduation rates, were more likely to be receiving
      public health insurance and have diabetes. At one-year post-transplant, AAs had
      62% higher risk of graft loss (RR 1.62, 95% CI 1.50-1.75) which increased to 93%
      at five years (RR 1.93, 95% CI 1.85-2.01). Adjusted risk of graft loss,
      accounting for baseline characteristics, was 60% higher in AAs (HR 1.61 [1.52
      1.69]). AAs had significantly higher risk of acute rejection and delayed graft
      function. CONCLUSION: AAs continue to experience disproportionately high rates of
      graft loss within the contemporary era of transplant, which are related to a
      convergence of an array of socioeconomic and biologic risk factors.

PMID- 27887678
TI  - [Cushing's disease in a psychiatric setting].

PMID- 27887679
TI  - [Mindfulness-based interventions in obsessive-compulsive disorder: Mechanisms of
      action and presentation of a pilot study].
AB  - Obsessive-compulsive disorder (OCD) is a frequent and severe disease, potentially
      inducing a major impairment for the patient and burden for their family. Recent
      research in psychiatry and neuroscience have led to better comprehension of the
      disease's mechanisms and helped to improve its treatment. However, a large
      proportion of patients have refractory symptoms, including for traditional
      cognitive and behavioral therapy by exposure and response prevention (ERP),
      leading clinicians to look for new treatments. Mindfulness-based interventions
      (MBI) are a new type of approach, initially based on Buddhist meditation, which
      aims to provide better consciousness of the present moment. It has been
      successfully developed in some psychiatric diseases and other general medical
      conditions such as chronic pain. The two main programs using mindfulness
      meditation, Mindfulness-based stress reduction (MBSR) and Mindfulness-based
      cognitive therapy (MBCT), have shown effectiveness for the reduction of
      depressive and anxiety symptoms and relapses of depressive episodes in unipolar
      depression. It has no side effects and is well tolerated by patients. Its action
      relies on the specific correction of cognitive deficits in attention, emotion
      regulation and executive functions which are shared by OCD, GAD and depression.
      For OCD, we make the hypothesis that Mindfulness-Based Interventions could reduce
      the cognitive bias specifically existing in this pathology, such as dysfunctional
      beliefs, and therefore improve the symptoms. This article first reviews the
      existing literature on clinical trials involving Mindfulness-Based Interventions
      in OCD which comprises a small number of clinical studies based on very different
      types of protocols. At this time, and due to the lack of gold-standard studies
      with a large number of patients, no proof of the efficiency of mindfulness-based
      interventions in OCD has been shown. In a second section, following our
      hypothesis on the mechanisms of specific and non-specific action of this therapy
      in OCD, we propose a cognitive model of mindfulness-based therapy action in OCD
      involving the correction of OCD's cognitive bias. In this model, mindfulness
      based therapy is supposed to treat specifically the cognitive aspects of the
      disease, while ERP is focused on its behavioral part. Then we present a clinical
      study aiming to prove the feasibility and the interest of the use of mindfulness
      in OCD, carried out in two different clinical centers. One of them used MBCT
      while the second used MBSR. Its results show the feasibility of mindfulness-based
      therapy in OCD patients and tend to prove that it could be more effective in
      young patients suffering from less severe forms of OCD. In parallel, attention
      tests and fMRI scans were done at the beginning and at the end of the therapy.
      Their results will be published separately. We also discuss the putative role of
      a specific form of MBCT adapted for OCD, specifically for its benefits in
      psychoeducation, which could reduce the dysfunctional beliefs present in OCD
      patients. Finally, we propose a therapeutic strategy in which the MBCT could
      complement the classical ERP therapy, as a "maintenance" treatment, aiming to
      extend the relapse of OCD symptoms. This article is a step further in the use of
      mindfulness-based therapy for OCD which could be added to the existing treatments
      reducing the patient's symptoms and improving their quality of life.

PMID- 27887680
TI  - Emergency Video Telemedicine Consultation for Newborn Resuscitations: The Mayo
      Clinic Experience.
AB  - OBJECTIVE: To describe the Mayo Clinic experience with emergency video
      telemedicine consultations for high-risk newborn deliveries. PATIENTS AND
      METHODS: From March 26, 2013, through December 31, 2015, the Division of Neonatal
      Medicine offered newborn telemedicine consultations to 6 health system sites. A
      wireless tablet running secure video conferencing software was used by the local
      care teams. Descriptive data were collected on all consultations. After each
      telemedicine consult, a survey was sent to the neonatologist and referring
      provider to assess the technology, teamwork, and user satisfaction. RESULTS:
      During the study, neonatologists conducted 84 telemedicine consultations, and 64
      surveys were completed. Prematurity was the most frequent indication for
      consultation (n=32), followed by respiratory distress (n=15) and need for
      advanced resuscitation (n=14). After the consult, nearly one-third of the infants
      were able to remain in the local hospital. User assessment of the technology
      revealed that audio and video quality were poor or unusable in 16 (25%) and 12
      (18.8%) of cases, respectively. Providers failed to establish a video connection
      in 8 consults (9.5%). Despite technical issues, providers responded positively to
      multiple questions assessing teamwork (86.0% [n=37 of 43] to 100.0% [n=17 of 17]
      positive responses per question). In 93.3% (n=14 of 15) of surveyed cases, the
      local provider agreed that the telemedicine consult improved patient safety,
      quality of care, or both. CONCLUSION: Telemedicine consultation for neonatal
      resuscitation improves patient access to neonatology expertise and prevents
      unnecessary transfers to a higher level of care. A highly reliable technology
      infrastructure that provides high-quality audio and video should be considered
      for any emergency telemedicine service.

PMID- 27887681
TI  - Bone Accrual in Males with Autism Spectrum Disorder.
AB  - OBJECTIVE: To test the hypothesis that bone accrual over a 4-year period is
      reduced in boys with autism spectrum disorder (ASD) compared with typically
      developing controls. STUDY DESIGN: Twenty-five boys with ASD and 24 controls were
      assessed for bone outcomes. Fourteen boys with ASD and 11 controls were assessed
      both at baseline and after 4 years. The mean subject age was 11.0 +/- 1.6 years
      at study initiation and 14.9 +/- 1.6 years at follow-up. Bone mineral density
      (BMD) was measured at the spine, hip, and whole body using dual-energy X-ray
      absorptiometry and normalized for age, race, and sex (BMD z-scores). Height
      adjustments were performed as well. We assessed medical history, physical
      activity using questionnaires, vitamin D and calcium intake using food records,
      and serum calcium, phosphorus, 25(OH)-vitamin D, and pubertal hormone levels.
      RESULTS: Boys with ASD had lower spine, hip, and whole body BMD z-scores compared
      with controls. In those subjects assessed both at baseline and after 4 years,
      bone accrual rates did not differ between the 2 groups; however, spine and hip
      BMD z-scores remained lower in the boys with ASD than in controls at follow-up.
      Notably, the ASD group was less physically active at both time points.
      CONCLUSION: Although pubertal bone accrual was similar to that in controls, BMD
      in children with ASD remained low over a 4-year follow-up period, suggesting that
      low BMD is a consequence of prepubertal factors, such as low physical activity.
      Studies are needed to investigate the causes and consequences of decreased BMD,
      to assess BMD in females and adults with ASD, and to evaluate therapeutic
      interventions.

PMID- 27887682
TI  - Tracheal cartilage growth by intratracheal injection of basic fibroblast growth
      factor.
AB  - BACKGROUND/PURPOSE: We have previously shown that intratracheal injection of
      slowly released (in gelatin) basic fibroblast growth factor (bFGF) significantly
      enlarged the tracheal lumen by a slight margin. This study aimed to investigate
      differences in tracheal cartilage growth by the intratracheal injection of bFGF
      doses in a rabbit model. METHODS: Water (group 1; n=7; control) or 100MUg (group
      2; n=8) or 200MUg (group 3; n=8) of bFGF dissolved in water was injected into the
      posterior wall of the cervical trachea of New Zealand white rabbits using a
      tracheoscope. All animals were sacrificed four weeks later. RESULTS: The mean
      circumferences of cervical tracheas for groups 1, 2, and 3 were 18.8+/-0.83,
      21.1+/-2.0, and 22.1+/-1.3mm, respectively. A significant difference was found
      between groups 1 and 2 (P=0.034) and groups 1 and 3 (P=0.004). The mean luminal
      areas of cervical tracheas for groups 1, 2, and 3 were 27.0+/-2.1, 32.2+/-4.8,
      and 36.3+/-4.6mm2, respectively. A significant difference was found between
      groups 1 and 3 (P=0.001). CONCLUSION: Intratracheal injection of bFGF in the dose
      range used significantly promoted the growth of tracheal cartilage in a rabbit
      model. LEVELS OF EVIDENCE: Level II at treatment study (animal experiment).

PMID- 27887683
TI  - Sacral nerve stimulation allows for decreased antegrade continence enema use in
      children with severe constipation.
AB  - BACKGROUND: Sacral nerve stimulation (SNS) can be beneficial for children with
      constipation, but no studies have focused on children with constipation severe
      enough to require antegrade continence enemas (ACEs). Our objective was to
      evaluate the efficacy of SNS in children with constipation treated with ACE.
      METHODS: Using a prospective patient registry, we identified patients <21years
      old who were receiving ACE prior to SNS placement. We compared ACE/laxative
      usage, PedsQL Gastrointestinal Symptom Scale (GSS), Fecal Incontinence Quality of
      Life Scale (FIQL), Fecal Incontinence Severity Index (FISI), and Vancouver
      Dysfunctional Elimination Syndrome Score (DES) at baseline and progressive follow
      up time intervals. RESULTS: Twenty-two patients (55% male, median 12years) were
      included. Median ACE frequency decreased from 7 per week at baseline to 1 per
      week at 12months (p<0.0001). Ten children (45%) had their
      cecostomy/appendicostomy closed. Laxative use, GSS, FIQL, and DES did not change.
      FISI improved over the first 12months with statistical significance reached only
      at 6months (p=0.02). Six (27%) children experienced complications after SNS that
      required further surgery. CONCLUSIONS: In children with severe constipation
      dependent on ACE, SNS led to a steady decrease in ACE usage with nearly half of
      patients receiving cecostomy/appendicostomy closure within 2years. LEVEL OF
      EVIDENCE: IV.

PMID- 27887684
TI  - The relationship of red blood cell transfusion to intestinal mucosal injury in
      premature infants.
AB  - OBJECTIVE: To determine the incidence of intestinal mucosal injury before and
      after transfusions in premature infants. STUDY DESIGN: Urine was collected
      throughout the hospital stay of 62 premature infants and specimens obtained
      within 24h before and after transfusion were assayed for intestinal fatty acid
      binding protein (iFABP). A urinary iFABP:creatinine ratio (iFABPu:Cru) of
      2.0pg/nmol was considered elevated. RESULT: Forty-nine infants were transfused.
      iFABPu:Cru was elevated following 71 (75.6%) of 94 transfusions for which urine
      was available. In 51 (71.8%) of these, iFABPu:Cru was also elevated prior to the
      transfusion. Among four cases of transfusion-associated NEC, iFABPu was elevated
      following every sentinel transfusion and prior to three of them. CONCLUSION:
      Subclinical intestinal mucosal injury is frequent following blood transfusions in
      premature infants and, when present, usually precedes transfusion. This suggests
      that transfusion may not be a primary mediator of intestinal injury so much as
      anemia and its associated conditions. LEVEL OF EVIDENCE: Prognosis study/level 3.

PMID- 27887685
TI  - Reply to letter to the editor.

PMID- 27887686
TI  - Erratum for "Utility of Isoproterenol to Provoke Outflow Tract Gradients in
      Patients with Hypertrophic Cardiomyopathy" Am J Cardiol 2008;101:516-520.

PMID- 27887687
TI  - Comparison of Lower Extremity Endovascular Intervention Outcomes in Women Versus
      Men.
AB  - This study examined a gender difference in 12-month patient outcomes after
      endovascular intervention for symptomatic peripheral artery disease (PAD)
      utilizing propensity score-matched Excellence in Peripheral Artery Disease
      registry data. Mortality and repeat intervention outcomes after endovascular
      treatment in women compared with men in the existing literature are inconsistent
      and confounded by other risk factors. The study included 1,084 patients who
      underwent 1,702 endovascular procedures, at 8 non-Veterans Administration
      hospitals from January 2005 to October 2015. Frailty hazard ratios by gender for
      time-to-event analysis were estimated. Women made up about 40% of the study
      population. After propensity score matching, 449 women and 449 men were included
      in the analysis, in which women had similar baseline patient and lesion
      characteristics, laboratory data, procedural characteristics, and medical therapy
      as men. Within 12-month postintervention, women were at a lower risk of mortality
      than men (p = 0.05); however, they underwent significantly more frequent repeat
      revascularization procedures (p = 0.04). In subgroup analysis, women with
      superficial femoral artery disease were also at higher risk of 12-month repeat
      intervention than men (p <0.01) and had a higher mortality risk, albeit with an
      attenuated significance (p = 0.07). Women with PAD are at a higher risk of 12
      month repeat intervention than men.

PMID- 27887688
TI  - Long-Term Outcomes After Stent Implantation for Left Main Coronary Artery (from
      the Multicenter Assessing Optimal Percutaneous Coronary Intervention for Left
      Main Coronary Artery Stenting Registry).
AB  - We assessed long-term outcomes after left main coronary artery (LMCA) stenting
      based on lesion types and stenting strategies. In the Assessing Optimal
      percutaneous coronary Intervention for Left Main Coronary Artery stenting
      registry, we evaluated 1,607 consecutive patients undergoing stent implantation
      for unprotected LMCA lesions (bifurcation lesions: n = 1318 and nonbifurcation
      lesions: n = 289). Among the bifurcation lesions, 1,281 lesions were treated with
      stenting across the bifurcation (bifurcation 1-stent strategy: n = 999 or
      bifurcation 2-stent strategy: n = 282). Among the nonbifurcation lesions, 219
      lesions were treated with nonbifurcation stenting. The median follow-up duration
      was 4.6 (95% CI 4.5 to 4.8) years. The 5-year risk of bifurcation lesions
      relative to nonbifurcation lesions was neutral for target lesion
      revascularization (TLR) (adjusted hazard ratio [HR] 0.82, 95% CI 0.55 to 1.23, p
      = 0.34) and all-cause death (adjusted HR 1.22, 95% CI 0.87 to 1.71, p = 0.26).
      The risk of the bifurcation 1-stent strategy relative to nonbifurcation stenting
      in nonbifurcation lesions was also neutral for TLR (adjusted HR 1.19, 95% CI 0.74
      to 1.90, p = 0.47) and all-cause death (adjusted HR 0.81, 95% CI 0.56 to 1.18, p
      = 0.27). However, the bifurcation 2-stent strategy was associated with worse
      clinical outcomes than the bifurcation 1-stent strategy in TLR (adjusted HR 1.76,
      95% CI 1.23 to 2.52, p = 0.002) and definite or probable stent thrombosis (crude
      HR 3.50, 95% CI 1.32 to 9.33, p = 0.01), despite neutral risk for all-cause death
      (adjusted HR 1.00, 95% CI 0.74 to 1.36, p = 0.99). There was no definite or
      probable very late stent thrombosis up to 5 years. In conclusion, long-term
      outcomes after stent implantation for unprotected LMCA lesions were not dependent
      on the bifurcation lesion types but related to the bifurcation stenting
      strategies with worse outcomes for the bifurcation 2-stent strategy.

PMID- 27887689
TI  - Usefulness of Post-coronary Dilation to Prevent Recurrent Myocardial Infarction
      in Patients Treated With Percutaneous Coronary Intervention for Acute Coronary
      Syndrome (from the BASE ACS Trial).
AB  - Stent underexpansion is associated with worse outcome after stent implantation.
      Whether post-dilation (PD) improves outcome in patients with acute coronary
      syndrome (ACS) remains unclear. We performed post hoc analysis of outcome in
      patients from the BASE ACS (A prospective randomized comparison of titanium
      nitride-oxide-coated bioactive stents with everolimus-eluting stents in acute
      coronary syndrome) trial who underwent PD versus those who did not. The BASE ACS
      trial randomized 827 patients (1:1) with ACS to receive either titanium-nitride
      oxide-coated bioactive stents or everolimus-eluting stents. The primary end point
      was major adverse cardiac events (MACE): a composite of cardiac death, nonfatal
      myocardial infarction (MI), or ischemia-driven target lesion revascularization.
      Follow-up was planned at 12 months and yearly thereafter for up to 7 years. Of
      827 patients enrolled in the BASE ACS trial, 357 (43.2%) underwent PD. Median
      follow-up duration was 5 years. Patients who underwent PD had less frequent
      nonfatal MI events at long-term follow-up, compared with those who did not (4.5%
      vs 8.5%, respectively, p = 0.02). The rates of MACE (15.7% vs 15.1%,
      respectively, p = 0.81), and the other endpoints, were not significantly
      different (p >0.5 for all). The results were consistent in propensity score
      matched analysis (270 pairs). In patients treated with bioactive stents, those
      who underwent PD had a trend for a fewer nonfatal MI events (p = 0.076).
      Comparably, in patients treated with everolimus-eluting stents, MACE and all the
      individual end points were comparable (p >0.5 for all). In conclusion, patients
      treated with early percutaneous coronary intervention for ACS who underwent PD
      had less frequent nonfatal MI events at long-term follow-up, compared with those
      who did not; MACE rates were not significantly different.

PMID- 27887690
TI  - Relation of Mitochondrial DNA Copy Number in Peripheral Blood to Postoperative
      Atrial Fibrillation After Isolated Off-Pump Coronary Artery Bypass Grafting.
AB  - Oxidative stress has been considered to be an important factor contributing to
      postoperative atrial fibrillation (PoAF). Mitochondrial DNA (mtDNA) copy number
      in peripheral blood has been found to be associated with a patient's oxidative
      stress. Therefore, we sought to determine whether there was association between
      mtDNA copy number and the onset of atrial fibrillation. mtDNA copy numbers were
      measured using the quantitative real-time polymerase chain reaction in peripheral
      blood from 485 consecutive patients with sinus rhythm undergoing coronary artery
      bypass grafting. The blood was collected before surgery. In the cohort, the
      incidence of PoAF was 20.8% (101/485). The mean mtDNA copy number was
      significantly higher in patents with PoAF than in those with sinus rhythm (36.43
      vs 16.63, p <0.001). The receiver operating characteristic analysis proved that
      the mtDNA copy number could predict PoAF with good sensitivity and specificity
      (area under the curve = 0.814, cutoff = 20.91, sensitivity = 70.3%, specificity =
      80.2%, p <0.001). On multivariate logistic and Cox regression analysis, mtDNA
      copy number was shown to be a significant independent risk factor for PoAF (odds
      ratio = 10.01, p <0.001 and hazard ratio = 7.011, p = 0.004). There was a strong
      positive correlation between mtDNA copy number and malondialdehyde in patients
      with PoAF (r = 0.449, p = 0.01). In conclusion, we showed that elevated mtDNA
      copy number in peripheral blood is associated with PoAF. Further investigation is
      needed to validate mtDNA copy number as a predictive biomarker for PoAF and to
      explore its potential role in arrhythmogenesis.

PMID- 27887691
TI  - Cost Effectiveness of Achieving Targets of Low-Density Lipoprotein Particle
      Number Versus Low-Density Lipoprotein Cholesterol Level.
AB  - A recent analysis of a commercially insured US population found fewer
      cardiovascular disease (CVD) events in high-risk patients attaining low levels of
      low-density lipoprotein (LDL), as measured by LDL particle number (LDL-P) versus
      low LDL cholesterol (LDL-C). Here, we investigated the cost effectiveness of LDL
      lowering therapy guided by LDL-P. Patients were selected from the HealthCore
      Integrated Research Database and followed for 12 to 36 months. Patients who
      achieved LDL-P <1,000 nmol/l were placed into the LDL-P cohort, whereas those
      without LDL-P tests, but who achieved LDL-C <100 mg/dl, were placed into the LDL
      C cohort. CVD-related costs included all health plan paid amounts related to CVD
      events or lipid management. Cost effectiveness was assessed through incremental
      cost-effectiveness ratios, defined as difference in total costs across the
      cohorts divided by difference in CVD events, measured over follow-up. Each cohort
      included 2,094, 1,242, and 705 patients over 12-, 24-, and 36-month follow-up.
      Patients in the LDL-P cohort received more aggressive lipid-lowering therapy and
      had fewer CVD events during follow-up compared to patients in the LDL-C cohort.
      This led to greater pharmacy costs and lower medical costs over time. Incremental
      cost-effectiveness ratio estimates ranged from $23,131 per CVD event avoided at
      12 months to $3,439 and -$4,555 at 24- and 36-month follow-up, suggesting a high
      likelihood that achieving LDL-P <1,000 nmol/l is cost effective. In conclusion,
      LDL-lowering therapy guided by LDL-P was demonstrated to be cost effective, with
      greater clinical and economic benefit seen over longer time horizons and with the
      increased use of generic statins.

PMID- 27887692
TI  - Mechanisms of Effort Intolerance in Patients With Heart Failure and Borderline
      Ejection Fraction.
AB  - Combining echocardiography and cardiopulmonary stress testing allows noninvasive
      assessment of hemodynamics, and oxygen extraction (A-VO2 difference). We
      evaluated mechanisms of effort intolerance in patients with heart failure with
      borderline (40% to 49%) left ventricular ejection fraction (EF) (HF and
      Borderline Ejection fraction). We included 89 consecutive patients with HF and
      Borderline Ejection fraction (n = 25; 63.6 +/- 14 years, 64% men), control
      subjects (n = 22), patients with HF with preserved EF (n = 26; EF >=50%), and
      patients with HF with reduced EF (n = 16; <40%). Various echo parameters (left
      ventricular volumes, EF, stroke volume, mitral regurgitation [MR] volume, e',
      right ventricle end-diastolic area, and right ventricle end-systolic area), and
      ventilatory or combined parameters (peak oxygen consumption [VO2] and A-VO2
      difference) were measured at 4 predefined activity stages. Effort-induced
      functional MR was frequent and more prevalent in HF and Borderline Ejection
      fraction than in all the other types of HF. In multivariable analysis heart rate
      response (p <0.0001), A-VO2 difference (p = 0.02), stroke volume (p = 0.002), and
      right ventricle end-systolic area were the only independent predictors of
      exercise capacity in HF and Borderline Ejection fraction but peak EF was not. In
      HF and Borderline Ejection fraction exercise intolerance is predominantly due to
      chronotropic incompetence, peripheral factors, and limited stroke volume reserve,
      which are related to right ventricle dysfunction and functional MR but not to
      left ventricular ejection fraction. Combined testing can be helpful in
      determining mechanisms of exercise intolerance in HF and Borderline Ejection
      fraction.

PMID- 27887693
TI  - Reprint of "Survey and first molecular characterization of Echinococcus
      granulosus sensu stricto (G1) in Pampas fox (Lycalopex gymnocercus) in Buenos
      Aires province, Argentina".
AB  - Echinococcosis is a zoonosis caused by tapeworms of the genus Echinococcus.
      Echinococcus granulosus sensu lato (s. l.) has a world-wide distribution and its
      transmission is primarily maintained in a synanthropic cycle with dogs as
      definitive hosts and livestock species as intermediate hosts. However, many wild
      canids also function as definitive hosts for E. granulosus s. l. Echinococcosis
      in humans is mainly caused by E. granulosus sensu stricto (s. s.) G1 genotype. In
      the present work, we expanded the epidemiological study on echinococcosis
      reported cases in Pampas fox (Lycalopex gymnocercus) to provide a prevalence
      estimate for rural areas of southern Buenos Aires province, Argentina. Ninety
      five whole intestines were analyzed using the sedimentation and counting
      technique with a result of 83 foxes (87.37%) harboring at least one helminth
      species. E. granulosus s. l. adults were found in one Pampas fox (1.05%). These
      adult helminthes were E. granulosus s. s. (G1) according to the genotyping
      analysis of a 450-bp region of the mitochondrial cytochrome c oxidase subunit 1
      (cox1) gene.

PMID- 27887694
TI  - Reprint of "Assessing the impact of a joint human-porcine intervention package
      for Taenia solium control: Results of a pilot study from northern Lao PDR".
AB  - Following confirmation that a remote village of approximately 300 inhabitants in
      northern Lao PDR was hyperendemic for the Neglected Tropical Disease Taenia
      solium, a pilot human-porcine therapeutic control intervention was implemented
      between October 2013 and November 2014. Mass drug administration with a three day
      albendazole 400mg protocol was offered to all eligible humans in October 2013 and
      March 2014. At these times, and again in October 2014, eligible village pigs
      received the anti-cysticercosis TSOL18 vaccination and an oral dose of
      oxfendazole anthelmintic at 30mg/kg, both repeated one month later. Community and
      individual human taeniasis prevalences were estimated via copro-antigen ELISA of
      volunteered human faecal samples prior to October 2013, and again in January
      2015, in order to examine the short term impact of the intervention.

PMID- 27887695
TI  - Reprint of "Echinococcus granulosus sensu stricto (s.s.) from the critically
      endangered antelope Addax nasomaculatus in Tunisia".
AB  - Echinococcus granulosus sensu lato (s.l.) is a zoonotic disease highly endemic in
      Tunisia. Canids including stray and semi-stray dogs, jackals and foxes are known
      as definitive hosts and a wide range of ungulates have been shown to harbour the
      metacestode hydatid stage and may serve as intermediate hosts. Fertile hydatid
      cysts of Echinococcus equinus and E. granulosus sensu stricto (s.s.) were
      recently molecularly identified for the first time from Tunisian donkeys. E.
      granulosus (s.s.) was also identified from wild boars in Tunisia. Here we report
      the confirmation of hydatid cysts caused by E. granulosus (s.s.) in the
      critically endangered antelope, Addax nasomaculatus in Tunisia. DNA-based
      molecular analysis revealed that A. nasomaculatus was infected with E. granulosus
      (s.s.) which had a 100% identity with the main globally distributed E. granulosus
      (s.s.) (EgTu01) haplotype. Cysts of Taenia hydatigena (n=33) were also observed
      on the liver and in the body cavity. Due to their endangered status and their
      relatively small numbers, it is unlikely that hydatid infection of A.
      nasomaculatus will form a major contribution to the epidemiology and transmission
      of E. granulosus in Tunisia, but infection may result in pathology, morbidity and
      early mortality, and may still play a role in the perpetuation of the parasite in
      wildlife cycles.

PMID- 27887696
TI  - Reprint of "Neurocysticercosis-related mortality in Brazil, 2000-2011:
      Epidemiology of a neglected neurologic cause of death".
AB  - Neurocysticercosis (NCC) is an important cause of severe neurological disease
      mainly in low- and middle-income countries, but data on NCC mortality from
      endemic areas are scarce. Here we analysed the epidemiological patterns of NCC
      related mortality in Brazil. We included all deaths recorded in Brazil between
      2000 and 2011, in which NCC was mentioned on death certificates, either as
      underlying or as associated cause of death. NCC was identified in 1829/12,491,280
      deaths (0.015%), 1130 (61.8%) as underlying cause, and 699 (38.2%) as associated
      cause. Overall age-adjusted mortality rate for the period was 0.97
      deaths/1,000,000 inhabitants (95% confidence interval [CI]: 0.83-1.12). The
      highest NCC-related mortality rates were found in males, elderly, white
      race/colour and residents in endemic states/regions. Age-adjusted mortality rates
      at national level decreased significantly over time (annual percent change [APC]:
      -4.7; 95% CI: -6.0 to -3.3), with a decrease in the Southeast, South and Central
      West regions, and a non-significant increasing trend in the North and Northeast
      regions. We identified spatial and spatiotemporal high-risk mortality clusters
      located mainly in NCC-endemic areas. Conditions related to the nervous system
      were the most commonly associated causes of death when NCC was mentioned as an
      underlying cause, and HIV/AIDS was the main underlying cause when NCC was an
      associated cause. NCC is a neglected and preventable cause of severe neurologic
      disease and death with high public health impact in Brazil. There is a clear need
      to strengthen nationwide epidemiological surveillance and control for the
      taeniasis/cysticercosis complex.

PMID- 27887697
TI  - Hypercrosslinked cholesterol-based polystyrene monolithic capillary columns.
AB  - Cholesteryl methacrylate has been used to obtain hypercrosslinked
      poly(cholesteryl methacrylate-co-4-methylstyrene-co-vinylbenzyl chloride-co
      divinylbenzene) monolithic stationary phase for capillary liquid chromatography.
      Different contents of cholesteryl methacrylate and toluene in polymerization
      mixture have been tested to obtain chromatographic performance. The best column
      has been prepared using 7% of cholesteryl methacrylate and 1% of toluene in
      polymerization mixture. Such a monolithic material exhibited a surface area of
      452m2/g (BET). The column efficiency of about 63 000 plates/m (H=15MUm) was
      achieved for benzene. The polystyrene column with cholesteryl methacrylate
      providing an additional functional group gave the highest efficiency compared to
      known poly(4-methylstyrene-co-vinylbenzyl chloride-co-divinylbenzene) and
      poly(cholesteryl methacrylate-co-trimethylolpropane trimethacrylate) monolithic
      columns. All of the above capillary columns were used for the separations of
      small molecules, such as alkylbenzenes, o-terphenyl/triphenylene, parabens, and
      proteins in reversed-phase liquid chromatography mode. The relative standard
      deviation of day-to-day reproducibility of hypercrosslinked poly(cholesteryl
      methacrylate-co-4-methylstyrene-co-vinylbenzyl chloride-co-divinylbenzene)
      monolithic columns were between 12.39-15.95% for retention factors and 10-24% for
      plate heights, respectively.

PMID- 27887698
TI  - Simultaneous extraction of polycyclic aromatic hydrocarbons through the complete
      dissolution of solid biological samples in sodium hydroxide/urea/thiourea aqueous
      solution.
AB  - In order to precisely and simultaneously extract polycyclic aromatic hydrocarbons
      (PAHs) for measurement using a high performance liquid chromatography
      fluorescence detector (HPLC-FL), a novel sample preparation method was developed.
      This method is based on the complete and fast dissolution of biological samples
      in a new non-alcoholic alkaline medium. A solution composed of NaOH/urea/thiourea
      at an optimized ratio was used for complete dissolution of approximately 0.25g
      dried fish samples within 20min. The proposed method was conducted at 10 degrees
      C and under atmospheric pressure to obtain a stable and highly homogeneous
      solution, without the need for microwaves or any other apparatus. This process
      operates at considerably lower temperature than conventional methods and provides
      an opportunity to simultaneously extract the target analytes from their matrices
      by adding the extracting solvent in the initial steps of the dissolution; this
      process greatly reduced the time of analysis and the loss of analytes via
      vaporization. Several key parameters were identified and their effects on
      precision and extraction recoveries were investigated. Linearity over a
      calibration range of 1.0-100 and 2.5-100ngg-1 was achieved, with high
      coefficients of determination (r2) ranging between 0.9987 and 0.9998. Based on
      relative standard deviations (n=5), the intra-day and inter-day precisions of the
      spiked PAHs were found to be better than 3.1% and 3.2%, respectively, at a
      concentration level of 25ngg-1. The recoveries of PAH from spiked marine fish
      tissues and shrimp samples were in the range of 90.6%-100.4%. The spiked samples
      were also treated with the alcoholic alkaline and Soxhlet extraction methods in
      order to provide a comparison.

PMID- 27887699
TI  - An improved method for the analysis of 2-aminoacetophenone in wine based on
      headspace solid-phase microextraction and heart-cut multidimensional gas
      chromatography with selective detection by tandem mass spectrometry.
AB  - Heart-cut multidimensional gas chromatography coupled to selective mass
      spectrometric detection (H/C MDGC-MS-MS) was shown to be a suitable combination
      for analysis of the key component for the wine off-flavor named "atypical aging
      off-flavor" (german: "Untypische Alterungsnote", UTA), 2-aminoacetophenone (2
      AAP). Headspace solid phase microextraction (HS-SPME) was applied as an easy to
      automate sample preparation step suiting routine control situations. During
      method development two critical aspects were found, of which one is the chemical
      degradation of the neat substance, leading to signal reduction and a false
      response behavior. A second aspect is the pH stability of the deuterated
      isotopologue 1-(2-aminophenyl)-2,2,2-trideuterio-ethanone (2-AAP-d3) used for
      quantification via a stable isotope dilution assay. Despite an earlier suggestion
      to increase the extractable amount of 2-AAP and its isotopic standard in the
      headspace, alkalization of 2-AAP-d3 containing aqueous samples were found to be
      critical. In such a milieu a deuterium exchange can then cause erroneous
      quantitative results. The method proposed in our study thus uses native wine pH
      conditions and proved to be suitable for routine control with respect to the
      detection of the "atypical aging off-flavor" in wine at concentration levels
      below its sensory threshold of about 1MUgL-1. Good linearity was obtained in the
      calibrated range from 0.1-8MUgL-1 (y=1,2338x+0,1029, R=0,9985) with limits of
      detection or quantification being 0.01 and 0.14MUg/L, respectively.

PMID- 27887700
TI  - Advances in downstream processing of biologics - Spectroscopy: An emerging
      process analytical technology.
AB  - Process analytical technologies (PAT) for the manufacturing of biologics have
      drawn increased interest in the last decade. Besides being encouraged by the Food
      and Drug Administration's (FDA's) PAT initiative, PAT promises to improve process
      understanding, reduce overall production costs and help to implement continuous
      manufacturing. This article focuses on spectroscopic tools for PAT in downstream
      processing (DSP). Recent advances and future perspectives will be reviewed. In
      order to exploit the full potential of gathered data, chemometric tools are
      widely used for the evaluation of complex spectroscopic information. Thus, an
      introduction into the field will be given.

PMID- 27887701
TI  - More than 170 polyunsaturated tocopherol-related compounds in a vitamin E
      capsule: Countercurrent chromatographic enrichment, gas chromatography/mass
      spectrometry analysis and preliminary identification of the potential artefacts.
AB  - Tocopherols and tocotrienols (usually summed up as vitamin E) are a class of
      structurally related natural antioxidants. Commonly, only some of the eight
      classic representatives (four tocopherols and four tocotrienols) are found with
      varied composition in food. In this study we fractionated 230mg oil from
      commercial vitamin E supplement capsules by countercurrent chromatography (CCC)
      and subsequent analysis by gas chromatography with mass spectrometry (GC/MS) of
      silylated CCC fractions showed that these eight isomers represented only about
      70% of total tocopherol compounds. Detailed analysis enabled the detection of
      161T3 isomers (alpha-, gamma- and delta-T3) along with 18 tetra- and several
      penta-unsaturated isomers (tocools), two tocomonoenol isomers, and several
      degradation products with shorter isoprenoid side chain (apo-tocools).
      Altogether, over 170 tocool compounds, most likely artefacts which originated
      from an inappropriate oil refining process were described in this study. Silver
      ion high performance liquid chromatography (Ag+-HPLC) was used to separate one
      fraction rich in gamma-T3 into four peaks each consisting of at least five peaks
      according to GC/MS. About ten gamma-T3 isomers were also detected in rice bran
      oils from one producer bought retail in Germany.

PMID- 27887702
TI  - Wiring technique for lesser trochanter fixation in proximal IM nailing of
      unstable intertrochanteric fractures: A modified candy-package wiring technique.
AB  - INTRODUCTION: The purpose of this study was to introduce a new surgical
      technique, that involves modified Candy-package wiring followed by IM nailing
      fixation and to determine the clinical and radiological results obtained in
      patients with unstable intertrochanteric fractures with a lesser trochanter
      fragment. MATERIALS AND METHODS: This study included 22 patients who were
      undergone proximal IM nailing with lesser trochanter wiring between January 2014
      to June 2015. All patients were treated with minimally invasive technique of
      candy-package wiring for lesser trochanter fragments. The mean age was 75.8 years
      (range, 53-88) and average follow-up period was 15.1 months (range, 12-24). Each
      patient was followed up for a minimum of 12 months and their clinical and
      radiological results were analyzed. RESULTS: The mean period required for
      fracture union was 16.6 weeks. (range, 8-25) and union was successfully completed
      in all cases. The WOMAC scores at the last F/U visit (average; 45.4, range; 21
      75) were not significantly different to pre-trauma status (average; 36.5, range;
      19-59) (p=0.087). In comparison of ambulatory capacity prior to trauma,
      ambulatory aggravation was noted in four cases (18.2%), and eighteen cases
      (81.8%) was sustained walking ability of prior of trauma. Wiring breakage was
      found in two cases and heterotrophic ossification in one case. There were no
      functional deficeit related to the radiologic finding in these patients. With
      regard to postoperative complications, were no cut-outs, breakage, or pullout of
      screws. CONCLUSION: When surgically repairing unstable intertrochanteric
      fractures with lesser trochanter comminution using proximal IM nailing method,
      the modified Candy-packaging wiring technique increases the fixation force at the
      fracture site. Thus, through this technique, both firm fixation of the lesser
      trochanter and more stable bony union were obtained.

PMID- 27887703
TI  - The Delphi method: A tool to support injury control and trauma care policy.

PMID- 27887704
TI  - Aberrant modulation of brain activation by emotional valence during self
      referential processing among patients with delusions of reference.
AB  - BACKGROUND AND OBJECTIVES: Delusions of reference are thought to reflect
      abnormally heightened attributions of salience to mundane events or stimuli that
      lead to convictions that they are personally significant or directed at the
      observer. Recent findings highlight abnormal recruitment of brain regions
      associated with self-referential processes among patients with referential
      delusions. Given the inherent overlap of emotion, incentive salience, and self
      relevance, as well as with aberrant thought processes in psychosis, this study
      investigated the implicit relations between participants' perception of the
      emotional valence of stimuli on neural correlates of self-referent judgments
      among schizophrenia-spectrum patients with referential delusions. METHODS: During
      fMRI scanning, participants indicated whether sentences describing personal
      characteristics seemed to refer specifically to them. Subsequently, participants
      rated their perceived emotional valence of each statement. RESULTS: Regression
      analyses revealed differential relations between groups across regions associated
      with self-referential processing, including prefrontal regions, anterior
      cingulate, insula, precuneus, and dorsal striatum. Within these regions, greater
      activation related to sentences rated as more positive among healthy comparison
      participants and more negative among patients. LIMITATIONS: The current results
      warrant replication and extension with larger and longitudinal samples to assess
      potential moderating relations of clinical and demographic individual
      differences. CONCLUSIONS: These findings support aberrant brain activation
      associated with emotional and salience brain networks in schizophrenia and
      highlight the importance of considering specific emotional attributes (valence)
      in discrete domains of delusional thought (self-referential communication).

PMID- 27887705
TI  - Perceptions on the surgical treatment of inflammatory bowel disease in Spain.
      Results of a national survey.
AB  - INTRODUCTION: The incidence of inflammatory bowel disease (IBD) is increasing in
      Spain but there is little information on the availability of multidisciplinary
      care. This study aims to assess surgeon's opinions on the current situation of
      surgery for IBD in Spain. METHODS: An electronic closed survey was sent to
      members of the Spanish Association of Surgeons (AEC) from January to March 2015.
      This was a 52-item anonymised questionnaire with questions about how the
      treatment of IBD patients is organized in each centre, the existence of specific
      units, the management strategy in IBD patients, and the opinion of colorectal,
      general and trainee surgeons about the surgical treatment of IBD in their centre
      and in Spain. RESULTS: One hundred and ninety-two surgeons responded. Most
      participants work in tertiary hospitals (45%), most of them from different
      hospitals, some from the same hospital. Only 50% of hospitals have
      multidisciplinary teams for IBD. The initial approach is laparoscopic in 56% of
      cases, and 80% of participants in centres with multidisciplinary teams consider
      the timing of surgery to be appropriate. The annual number of IBD surgeries in
      tertiary hospitals is higher than in secondary hospitals in ulcerative colitis
      (57 vs. 24% 10-15 patients/year, P<.001) and Crohn's disease (68 vs. 28% 3-5
      patients/month, P<.001). Most centres operate less than 10 ulcerative colitis
      patients per year, even larger centres (67%) and they perform <=3 J-pouches/month
      (ulcerative colitis and other indications) (P<.001). Ninety-five percent of
      surgeons consider that centralization of complex cases in specialized units and
      the creation of national registries should be developed. The majority of
      participants (70%) believe that there is a deficit in research and educational
      activities in IBD surgery in Spain. CONCLUSION: This survey suggests that most
      Spanish hospitals have a low volume of IBD surgery, even large tertiary
      hospitals, and many centres do not have a multidisciplinary team dedicated to IBD
      patients. Most survey participants believe it is necessary to develop registries
      and increase training and research in IBD surgery in Spain.

PMID- 27887706
TI  - Sectorization of medical and surgical management of inflammatory bowel disease.

PMID- 27887707
TI  - [Usefulness of social and educational approach in adolescents and young adults
      with cancer: The Lille team's experience].
AB  - Within the second "Cancer plan" 2009-2013, the French national institute of
      cancer (INCa) recommended the implementation of programs dedicated to adolescents
      and youngs adults (AYA) with cancer. In this context and in parallel to the
      specific medical care developed for AYA, the Oscar-Lambret center created a
      psycho-social-educational team including among others a social worker (SW) and a
      special educational teacher (SET), offering multidisciplinary qualifications and
      views. The social approach, realized as a pair by SW-SET, takes into account
      every aspect of each AYA (family, academic, career/professional, personal,
      cultural aspects...). We expose the first 2 years' experience of this special
      program for AYA through diagnosis to remission time. For this period, 164 AYA
      were seen by the social professionals, with a total of 602 consultations in the
      unit. The number of these consultations depended on the needs of AYA and their
      family. Nevertheless, only 10 AYA required no further intervention (6.1 %). The
      study highlights that the social interventions are most frequently about
      scolarity, work and disability recognition. These 2 years of experience of the SW
      SET team offered a way to reflect upon our values and our culture, and on the
      role of the social worker in a medical setting. Each AYA has a personal story,
      which affects significantly the way to overcome the challenges that come with the
      disease. Our findings underscore the need for AYA with cancer to have access to
      personalized supportive care, encouraging them in pursing their personal goals
      and rewarding themselves.

PMID- 27887708
TI  - Pulsatile gonadotropin-releasing hormone therapy in persistent amenorrheic weight
      recovered anorexia nervosa patients.
AB  - OBJECTIVE: To compare hormonal and clinical responses to GnRH pulsatile treatment
      in weight-recovered anorexia nervosa patients (Rec-AN) with persistent functional
      hypothalamic amenorrhea (HA) vs. in patients with secondary and primary HA.
      DESIGN: Retrospective, observational, ambulatory study. SETTING: University
      hospital. PATIENT(S): Forty-one women: 19 Rec-AN (body mass index >18.5 kg/m2
      without menses recovery), 15 secondary HA without any eating disorders patients
      (SHA), and 7 primary HA patients (PHA). INTERVENTION(S): Gonadotropin-releasing
      hormone pulsatile therapy. MAIN OUTCOME MEASURE(S): Baseline E2, LH, and P plasma
      levels and their changes during induction cycles; ovulation, follicular
      recruitment, and pregnancies. RESULTS: The Rec-AN group displayed higher basal E2
      and LH plasma levels after GnRH injection compared with SHA and PHA. Higher E2
      and LH levels were observed during induction cycles in Rec-AN compared with SHA
      and PHA. Follicular recruitment was higher in Rec-AN. The ovulation rate was
      higher in Rec-AN compared with PHA but similar to SHA. CONCLUSION(S): This study
      showed increased gonadal status and higher E2 response to pulsatile GnRH therapy
      in persistent amenorrheic weight-recovered AN compared with HA from other causes.
      It suggests that their individual set-point of body weight allowing a fully
      functional gonadal axis is not reached yet. Specific factors of gonadal inertia
      in Rec-AN still remain unclear.

PMID- 27887709
TI  - Impact of tamoxifen therapy on fertility in breast cancer survivors.
AB  - OBJECTIVE: To determine whether tamoxifen use is associated with decreased
      ovarian reserve and decreased likelihood of having a child after a breast cancer
      diagnosis, using data from the Furthering Understanding of Cancer, Health, and
      Survivorship in Adult (FUCHSIA) Women Study. DESIGN: Population-based cohort
      study. SETTING: Not applicable. PATIENT(S): Three hundred ninety-seven female
      breast cancer survivors aged 22-45 years whose cancer was diagnosed between ages
      20 and 35 years and who were at least 2 years after diagnosis; 108 survivors also
      participated in a clinic visit. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Time to first child after cancer diagnosis, clinical measures of ovarian reserve
      (antimullerian hormone [AMH] and antral follicle count [AFC]) after cancer.
      RESULT(S): Women who had ever used tamoxifen were substantially less likely to
      have a child after the breast cancer diagnosis (hazard ratio [HR] 0.29; 95%
      confidence interval [CI], 0.16, 0.54) than women who had never used tamoxifen.
      After adjusting for age at diagnosis, exposure to an alkylating agent, and race,
      the HR was 0.25 (95% CI, 0.14, 0.47). However, after adjusting for potential
      confounders, women who had used tamoxifen had an estimated geometric mean AMH
      level 2.47 times higher (95% CI, 1.08, 5.65) than women who had never taken
      tamoxifen. Antral follicle count was also higher in the tamoxifen group compared
      with the tamoxifen nonusers when adjusted for the same variables (risk ratio
      1.21; 95% CI, 0.84, 1.73). CONCLUSION(S): Breast cancer survivors who had used
      tamoxifen were less likely to have a child after breast cancer diagnosis compared
      with survivors who never used tamoxifen. However, tamoxifen users did not have
      decreased ovarian reserve compared with the tamoxifen nonusers.

PMID- 27887710
TI  - Supplementation with progestogens in the first trimester of pregnancy to prevent
      miscarriage in women with unexplained recurrent miscarriage: a systematic review
      and meta-analysis of randomized, controlled trials.
AB  - OBJECTIVE: To investigate whether treatment with progestogens in the first
      trimester of pregnancy would decrease the incidence of miscarriage in women with
      a history of unexplained recurrent miscarriage. DESIGN: Systematic review and
      meta-analysis. SETTING: Not applicable. PATIENT(S): Women with a history of
      unexplained recurrent miscarriage. INTERVENTION(S): Randomized, controlled trials
      were identified by searching electronic databases. We included randomized,
      controlled trials comparing supplementation with progestogens (i.e., intervention
      group) in the first trimester of pregnancy with control (either placebo or no
      treatment) in women with a history of recurrent miscarriage. All types of
      progestogens, including natural P and synthetic progestins, were analyzed. MAIN
      OUTCOME MEASURE(S): The primary outcome was the incidence of miscarriage. The
      summary measures were reported as relative risk (RR) with 95% confidence interval
      (CI). RESULT(S): Ten trials including 1,586 women with recurrent miscarriage were
      analyzed. Eight studies used placebo as control and were double-blind. Regarding
      the intervention, two RCTs used natural P, whereas the other eight studies used
      progestins: medroxyprogesterone, cyclopentylenol ether of progesterone,
      dydrogesterone, or 17-hydroxyprogesterone caproate. Pooled data from the 10
      trials showed that women with a history of unexplained recurrent miscarriage who
      were randomized to the progestogens group in the first trimester and before 16
      weeks had a lower risk of recurrent miscarriage (RR 0.72, 95% CI 0.53-0.97) and
      higher live birth rate (RR 1.07, 95% CI 1.02-1.15) compared with those who did
      not. No statistically significant differences were found in the other secondary
      outcomes, including preterm birth (RR 1.09, 95% CI 0.71-1.66), neonatal mortality
      (RR 1.80, 95% CI 0.44-7.34), and fetal genital abnormalities (RR 1.68, 95% CI
      0.22-12.62). CONCLUSION(S): Our findings provide evidence that supplementation
      with progestogens may reduce the incidence of recurrent miscarriages and seem to
      be safe for the fetuses. Synthetic progestogens, including weekly IM 17
      hydroxyprogesterone caproate, but not natural P, were associated with a lower
      risk of recurrent miscarriage. Given the limitations of the studies included in
      our meta-analysis, it is difficult to recommend route and dose of progestogen
      therapy. Further head-to-head trials of P types, dosing, and route of
      administration are required.

PMID- 27887711
TI  - Low body mass index compromises live birth rate in fresh transfer in vitro
      fertilization cycles: a retrospective study in a Chinese population.
AB  - OBJECTIVE: To evaluate the effects of low body mass index (BMI) on in vitro
      fertilization (IVF) outcomes in fresh transfer cycles. DESIGN: Retrospective
      cohort study. SETTING: University-affiliated hospital. PATIENT(S): A total of
      4,798 cycles with conventional stimulation and fresh transfer in a single IVF
      center during the period 2013-2014. Low BMI (<18.5 kg/m2) was defined according
      to World Health Organization guidelines, and cycles within a normal weight range
      (18.5-24.9 kg/m2) were used as reference. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Live birth rate per fresh embryo transfer. RESULT(S): Low BMI was
      associated with reduced live birth rates and increased miscarriage rates compared
      with normal weight, controlling for important covariates known to influence IVF
      outcomes. Patient age was the most potent confounder, causing a 10.5% reduction
      in the odds ratio (OR) for live birth between the groups compared. When an
      interaction term (age * BMI) was introduced, the OR for live birth was reduced in
      cycles of those aged >=35 years compared with cycles of those aged 28-34 years,
      whereas the change in OR between cycles in those aged <28 and cycles in those
      aged 28-34 years was insignificant. CONCLUSION(S): Low BMI is associated with
      negative outcomes in fresh transfer cycles, especially for women of advanced age.

PMID- 27887713
TI  - Magnetic resonance imaging correlation to intraoperative findings of deeply
      infiltrative endometriosis.
AB  - OBJECTIVE: To show characteristics of deeply infiltrative endometriosis (DIE) on
      magnetic resonance imaging (MRI) and how they correlate with intraoperative
      findings. DESIGN: Overview of still and dynamic MRI images of four different
      patients with DIE. We then used videos from their surgeries to highlight the
      appearance of endometriosis corresponding to these images (educational video).
      SETTING: University hospital. PATIENT(S): Four different patients with DIE were
      included in this video. These were all women of reproductive age who suffered
      from debilitating deeply infiltrative endometriosis. These patients had a pelvic
      MRI performed at our institution and subsequently underwent surgery with one of
      our minimally invasive gynecologic surgeons. INTERVENTION(S): The MRI
      endometriosis protocol includes T1-weighted fat and nonfat saturated as well as
      T2-weighted sequences. Images are taken along all three planes (axial, sagittal,
      and coronal) before and after contrast. What distinguishes the standard MRI from
      the endometriosis-protocol MRI is the thickness of the slices taken. For the
      evaluation of endometriosis, T1 nonfat saturated images are taken in 6-mm slices
      with no skip sections in between. Then, T1 fat saturated images and T2-weighted
      images are taken in 5-mm slices with a 1-mm skip section in between slices. The
      areas that are suspicious for lesions consistent with DIE are corroborated on
      videos taken during surgery. MAIN OUTCOME MEASURE(S): Value of accurate mapping
      of lesions with the use of preoperative MRI in surgical planning and complete
      resection of diseased tissue. RESULT(S): Results from a previously published
      prospective study by Bazot et al. reported sensitivity, specificity, positive
      predictive value, and negative predictive value of 90.3%, 91%, 92.1%, and 89%,
      respectively. Similarly to our institution, that study used a 1.5-T MRI, and the
      protocol of our institution closely mimicked the technique used in that study.
      Another prospective study published by Hottat et al. showed sensitivity,
      specificity, and positive and negative predictive values of MRI predicting
      intraoperative disease of 96.3%, 100%, 100%, and 93.3% respectively. Those
      results were gathered with the use of a 3.0-T MRI. The high accuracy in these
      studies of prediction of deep pelvic endometriosis in specific locations shows
      that MRI is effective for preoperative planning, as was the case for the four
      patients in our video. CONCLUSION(S): Preoperative planning for DIE with the use
      of MRI is integral in surgical planning. Other imaging modalities to diagnose
      DIE, such as transvaginal ultrasound, endoanal ultrasound, barium enema,
      cystoscopy, and rectoscopy, have all been used and studied for the evaluation of
      endometriosis. However, given its accuracy for mapping lesions, MRI could
      potentially replace multiple types of imaging while offering the best option for
      preoperative planning. Accurate mapping would result in greater success of
      resection and allow for multidisciplinary planning if necessary. Furthermore,
      being able to train the eye to identify lesions on MRI that are consistent with
      DIE is an asset to the gynecologic surgeon.

PMID- 27887714
TI  - Erratum.

PMID- 27887715
TI  - Focus on recurrent miscarriage phenotypes.

PMID- 27887716
TI  - Who requests their sperm donor's identity? The first ten years of information
      releases to adults with open-identity donors.
AB  - OBJECTIVE: To report findings from 10 years of requests from adults eligible to
      obtain their open-identity sperm donor's information. DESIGN: Analysis of
      archived family and donor data. Semistructured interviews at information
      releases. SETTING: Not applicable. PATIENT(S): A total of 85 DI adults requesting
      43 donor identities; program data on 256 DI families. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): We identified [1] demographic predictors of requesting donor
      identities, [2] information release timing and length, and [3] request motives.
      RESULT(S): Just >35% of eligible DI adults requested their donor's identity.
      Adults ranged from 18-27 years, requesting at median age 18 years. More women
      than men requested. Proportionally fewer adults requested when they had
      heterosexual-couple parents, and proportionally more when they had one rather
      than two parents. In interviews, the common theme was wanting to know more about
      the donor, especially about shared characteristics. Most adults planned to
      contact their donor. More than 94% of adults had donors who were open to contact;
      adults expressed modest expectations about this contact. CONCLUSION(S): In 2001,
      the first adults became eligible to obtain their open-identity sperm donor's
      information. Ten years of identity requests at one program indicates that
      information about one's donor is important to a significant proportion of these
      DI adults. Most requested their donor's identity soon after becoming eligible,
      suggesting some urgency to wanting the information. Interview data highlighted
      the role of donor information in helping adults better understand themselves and
      their ancestry. Findings hold important implications for practice and policy.

PMID- 27887717
TI  - Continued existence of significant disparities in the technical practices of
      sperm morphology assessment and the clinical implications: results of a French
      questionnaire.
AB  - OBJECTIVE: To investigate current practices for sperm morphology assessment.
      DESIGN: E-mail survey questionnaire. SETTING: Diagnostic and clinical
      institutions/laboratories. PATIENT(S): French biologists and clinicians (n =
      225). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Answers to 24 questions.
      RESULT(S): The survey shows that even now in France there is great inconsistency
      in the use of sperm morphology assessments. For example, the survey revealed that
      no fewer than six different staining techniques were in use. Automatic reading is
      hardly used (used by 2.5% of the biologists replying to the survey). More than
      33.6% of biologists use a threshold of normal forms unsuited to their
      classification, and 20% do not perform any internal quality control in this area.
      Prescribing doctors seldom trust the tests, likely due to their lack of analytic
      reliability. Among the biologists surveyed 26% said the percentage of normal
      forms is either unreliable or not very reliable in analytic terms, and 24% of
      clinicians stated that it has little clinical relevance. CONCLUSION(S): The
      survey reveals a marked lack of uniformity in French laboratories for performing
      sperm morphology assessment and in the use of the results by physicians. Regular
      quality control procedures and well-trained personnel, up to date with their
      training and conversant with the latest techniques as well as harmonized
      practices, are clearly indispensable. It is time for a consensus on the practice
      and interpretation of this particular test.

PMID- 27887718
TI  - Novel centrifugal technology for measuring sperm concentration in the home.
AB  - OBJECTIVE: To evaluate the analytical performance and usability of the Trak Male
      Fertility Testing System, a semiquantitative (categorical) device recently US
      Food and Drug Administration (FDA)-cleared for measuring sperm concentration in
      the home by untrained users. DESIGN: A three-site clinical trial comparing self
      reported lay user results versus reference results obtained by computer-aided
      semen analysis (CASA). SETTING: Simulated home use environments at fertility
      centers and urologist offices. PATIENT(S): A total of 239 untrained users.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sperm concentration results
      reported from self-testing lay users and laboratory reference method by CASA were
      evaluated semiquantitatively against the device's clinical cutoffs of 15 M/mL
      (current World Health Organization cutoff) and 55 M/mL (associated with faster
      time to pregnancy). Additional reported metrics include assay linearity,
      precision, limit of detection, and ease-of-use ratings from lay users. RESULT(S):
      Lay users achieved an accuracy (versus the reference) of 93.3% (95% confidence
      interval [CI] 84.1%-97.4%) for results categorized as <=15 M/mL, 82.4% (95% CI
      73.3%-88.9%) for results categorized as 15-55 M/mL, and 95.5% (95% CI 88.9%
      98.2%) for results categorized as >55 M/mL. When measured quantitatively, Trak
      results had a strong linear correlation with CASA measurements (r = 0.99). The
      precision and limit of detection studies show that the device has adequate
      reproducibility and detection range for home use. Subjects generally rated the
      device as easy to use. CONCLUSION(S): The Trak System is an accurate tool for
      semiquantitatively measuring sperm concentration in the home. The system may
      enable screening and longitudinal assessment of sperm concentration at home.
      CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02475395.

PMID- 27887719
TI  - Leucine-rich repeat-containing G-protein-coupled receptor 5-positive cells in the
      endometrial stem cell niche.
AB  - OBJECTIVE: To study, isolate and characterize leucine-rich repeat-containing
      heterotrimeric guanine nucleotide-binding protein-coupled receptor 5 (LGR5)
      positive cells from human endometrium to determine their functional relevance.
      DESIGN: Prospective experimental animal study. SETTING: University research
      laboratories. ANIMAL(S): Nonobese diabetic mice (NOD-SCID) (strain code 394;
      NOD.CB17-Prkdcscid/NcrCrl). INTERVENTION(S): Human LGR5+ cells were labeled with
      superparamagnetic iron oxide nanoparticles (SPIOs) and injected under the kidney
      capsule in immunocompromised mice. MAIN OUTCOME MEASURE(S): Epithelial and
      stromal LGR5+ cells were isolated from human endometrium by means of fluorescence
      activated cell sorting, and phenotypic characterization was performed by means of
      flow cytometry with the use of hematopoietic and mesenchymal markers. Engrafted
      SPIO-labeled LGR5+ cells were localized with the use of Prussian blue staining
      and immunohistochemistry against CD9 and Vimentin. Deep transcriptomic profiling
      of LGR5+ cells was performed with the use of microarrays and RNA sequencing.
      RESULT(S): The percentage of LGR5+ cells in human endometrium represented 1.08 +/
      0.73% and 0.82 +/- 0.76% of total cells in the epithelial and stromal
      compartments, respectively. LGR5+ cells were phenotypically characterized by
      abundant expression of CD45 hematopoietic marker and no expression of surface
      markers CD31, CD34, CD133, CD73, and CD90. Coexpression with the macrophage
      marker CD163 was detected. Xenotransplantation of labeled LGR5+ cells into the
      kidney capsules of immunocompromised mice resulted in a weak endometrial
      reconstitution from this cell of origin. Transcriptomic profiling revealed new
      attributes for LGR5+ cells related to their putative hematopoietic origin.
      CONCLUSION(S): These data suggest that endometrial LGR5 is not an endogenous stem
      cell marker. Instead, LGR5+ cells appear to be recruited from blood to be part of
      the stem cell niche at the perivascular microenvironment to activate the
      endogenous niche.

PMID- 27887720
TI  - Prehospital electrocardiographic acuteness score of ischemia is inversely
      associated with neurohormonal activation in STEMI patients with severe ischemia.
AB  - BACKGROUND: Elevated levels of N-terminal pro brain natriuretic peptide (NT
      proBNP) are associated with adverse cardiovascular outcome after ST elevation
      myocardial infarction (STEMI). We hypothesized that decreasing acuteness-score
      (based on the electrocardiographic score by Anderson-Wilkins acuteness score of
      myocardial ischemia) is associated with increasing NT-proBNP levels and the
      impact of decreasing acuteness-score on NT-proBNP levels is substantial in STEMI
      patients with severe ischemia. METHODS: In 186 STEMI patients treated with
      primary percutaneous coronary intervention (pPCI), the severity of ischemia
      (according to Sclarovsky-Birnbaum severity grades of ischemia) and the acuteness
      score were obtained from prehospital ECG. Patients were classified according to
      the presence of severe ischemia or non-severe ischemia and acute ischemia or non
      acute ischemia. Plasma NT-proBNP (pmol/L) was obtained after pPCI within 24hours
      of admission and was correlated with the acuteness-score. RESULTS: NT-proBNP
      levels were median (25th-75th interquartile) 112 (51-219) pmol/L in patients with
      non-severe ischemia (71.5%) and 145 (79-339) in patients with severe ischemia
      (28.5%) (p=0.074). NT-proBNP levels were highest in patients with severe and non
      acute ischemia compared to those with severe and acute ischemia (182 (98-339)
      pmol/L vs 105 (28-324) pmol/L, p=0.012). There was a negative correlation between
      acuteness-score and log(NT-proBNP) in patients with severe ischemia (r=0.395,
      p=0.003), which remained significant in multilinear regression analysis (beta=
      0.155, p=0.007). No correlation was observed between the acuteness-score and
      log(NT-proBNP) in patients with non-severe ischemia (p=0.529) or in the entire
      population (p=0.187). CONCLUSION: In STEMI patients with severe ischemia,
      neurohormonal activation is inversely associated with ECG patterns of acute
      myocardial ischemia.

PMID- 27887721
TI  - Comparative Multimodal Meta-analysis of Structural and Functional Brain
      Abnormalities in Autism Spectrum Disorder and Obsessive-Compulsive Disorder.
AB  - BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder
      (OCD) share inhibitory control deficits possibly underlying poor control over
      stereotyped and repetitive and compulsive behaviors, respectively. However, it is
      unclear whether these symptom profiles are mediated by common or distinct neural
      profiles. This comparative multimodal meta-analysis assessed shared and disorder
      specific neuroanatomy and neurofunction of inhibitory functions. METHODS: A
      comparative meta-analysis of 62 voxel-based morphometry and 26 functional
      magnetic resonance imaging (fMRI) studies of inhibitory control was conducted
      comparing gray matter volume and activation abnormalities between patients with
      ASD (structural MRI: 911; fMRI: 188) and OCD (structural MRI: 928; fMRI: 247) and
      control subjects. Multimodal meta-analysis compared groups across voxel-based
      morphometry and fMRI. RESULTS: Both disorders shared reduced function and
      structure in the rostral and dorsomedial prefrontal cortex including the anterior
      cingulate. OCD patients had a disorder-specific increase in structure and
      function of left basal ganglia (BG) and insula relative to control subjects and
      ASD patients, who had reduced right BG and insula volumes versus OCD patients. In
      fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal
      activation and reduced posterior cingulate deactivation, whereas OCD patients
      showed temporoparietal underactivation. CONCLUSIONS: The multimodal comparative
      meta-analysis shows shared and disorder-specific abnormalities. Whereas the
      rostrodorsomedial prefrontal cortex was smaller in structure and function in both
      disorders, this was concomitant with increased structure and function in BG and
      insula in OCD patients, but a reduction in ASD patients, presumably reflecting a
      disorder-specific frontostriatoinsular dysregulation in OCD in the form of poor
      frontal control over overactive BG, and a frontostriatoinsular maldevelopment in
      ASD with reduced structure and function in this network. Disorder-differential
      mechanisms appear to drive overlapping phenotypes of inhibitory control
      abnormalities in patients with ASD and OCD.

PMID- 27887722
TI  - The Effect of Specific Surface Area of Chitin-Metal Silicate Coprocessed
      Excipient on the Chemical Decomposition of Cefotaxime Sodium.
AB  - Chitin-metal silicates are multifunctional excipients used in tablets.
      Previously, a correlation between the surface acidity of chitin-calcium and
      chitin-magnesium silicate and the chemical decomposition of cefotaxime sodium was
      found but not with chitin-aluminum silicate. This lack of correlation could be
      due to the catalytic effect of silica alumina or the difference in surface area
      of the excipients. The objective of this study was to investigate the effect of
      the specific surface area of the excipient on the chemical decomposition of
      cefotaxime sodium in the solid state. Chitin was purified and coprocessed with
      different metal silicates to prepare the excipients. The specific surface area
      was determined using gas adsorption. The chemical decomposition was studied at
      constant temperature and relative humidity. Also, the degradation in solution was
      studied. A correlation was found between the degradation rate constant and the
      surface area of chitin-aluminum and chitin-calcium silicate but not with chitin
      magnesium silicate. This was due to the small average pore diameter of this
      excipient. Also, the degradation in solution was slower than in solid state. In
      conclusion, the stability of cefotaxime sodium was dependent on the surface area
      of the excipient in contact with the drug.

PMID- 27887723
TI  - Synergistic Effect of Cavitation and Agitation on Protein Aggregation.
AB  - It was recently reported that dropping induces protein aggregation due to the
      occurrence of cavitation. Agitation also causes protein aggregation. In this
      study, vials filled with antibody solution were subjected to a cycle of dropping
      and shaking using the friability testing apparatus to examine the combined effect
      of cavitation and agitation on protein aggregation. A cycle of dropping and
      shaking generated a massive amount of subvisible particles. Comparison of
      aggregation rate at different fill volumes indicated that shaking plays an
      important role in protein aggregation due to combination stress. Furthermore, the
      impact of dropping on aggregate formation was apparent because aggregation rate
      under combination stress was much faster than that under shaking stress alone.
      Increase in aggregate concentration was observed after shaking of the antibody
      solution, which was freshly filled into vials that had been previously used in
      the dropping and shaking test. Polysorbate 80 was effective in inhibiting
      aggregate formation under combination stress. These results suggest the following
      particle formation pathway: cavitation caused by dropping promotes antibody
      unfolding, the unfolded antibodies adsorb on the inner surface of the vial, and
      subsequent shaking yields subvisible particles by desorbing the adsorbed
      antibodies.

PMID- 27887724
TI  - Facial deformations during nasal continuous positive airway pressure therapy.
AB  - Obstructive Sleep Apnoea (OSA), characterised by repeated collapse of the
      pharyngeal airway during sleep, causes cessation of breathing followed by
      arousal, restoring normality. Continuous Positive Airway Pressure (CPAP) is a non
      invasive, effective treatment for OSA where positive pressure is applied to the
      airway through a mask, maintaining patency. Nasal masks are commonly used,
      contacting the face across the upper lip, sides of the nose and the nasal bridge.
      Despite health benefits, therapy compliance is sub-optimal, often due to poor
      mask fit and discomfort. Masks have been designed to conform to the facial
      profile, but have not taken into account facial deformations. The nature of
      facial deformations while undergoing CPAP therapy is unknown. This study
      investigates the facial deformations experienced by a patient while undergoing
      nasal CPAP therapy. Magnetic Resonance Imaging (MRI) scans of the face were
      acquired of participants in the reference configuration and while undergoing CPAP
      therapy. The CPAP scan volume was registered onto the reference volume prior to
      surface generation for each state. Perpendicular deformation was measured from
      the reference facial profile to the deformed profile. Large facial deformations
      were measured at the sides of the nose (4.6+/-1.6mm) and the upper lip (4.9+/
      1.8mm) with much smaller deformations at the nasal bridge (2.4+/-0.2mm). When
      normalised by applied load and tissue thickness, no difference was found. These
      findings and techniques can be used to consider facial deformation in the
      development of future nasal CPAP masks to improve comfort and compliance to
      therapy.

PMID- 27887725
TI  - A calcified polymeric valve for valve-in-valve applications.
AB  - The prevalence of aortic valve stenosis (AS) is increasing in the aging society.
      More recently, novel treatments and devices for AS, especially transcatheter
      aortic valve replacement (TAVR) have significantly changed the therapeutic
      approach to this disease. Research and development related to TAVR require
      testing these devices in the calcified heart valves that closely mimic a native
      calcific valve. However, no animal model of AS has yet been available.
      Alternatively, animals with normal aortic valve that are currently used for TAVR
      experiments do not closely replicate the aortic valve pathology required for
      proper testing of these devices. To solve this limitation, for the first time, we
      developed a novel polymeric valve whose leaflets possess calcium hydroxyapatite
      inclusions immersed in them. This study reports the characteristics and
      feasibility of these valves. Two types of the polymeric valve, i.e., moderate and
      severe calcified AS models were developed and tested by deploying a transcatheter
      valve in those and measuring the related hemodynamics. The valves were tested in
      a heart flow simulator, and were studied using echocardiography. Our results
      showed high echogenicity of the polymeric valve, that was correlated to the
      severity of the calcification. Aortic valve area of the polymeric valves was
      measured, and the severity of stenosis was defined according to the clinical
      guidelines. Accordingly, we showed that these novel polymeric valves closely
      mimic AS, and can be a desired cost-saving solution for testing the performance
      of the transcatheter aortic valve systems in vitro.

PMID- 27887726
TI  - Visualisation studies and glomerular filtration in early diabetic rats.
AB  - The purpose of this mini-review is to show that more modern multi-photon
      microscopy approaches allow quantitative glomerular filtration experiments.
      Modern science has now entered a transition period from light microscopy to multi
      photon confocal microscopy. Since the late 20th century, multi-photon microscopy
      has been applied in the study of organ function. In keeping with observations
      made in renal physiology and other representative studies throughout this
      transition period, and in the context of advancing microscopy techniques, this
      review has been presented as a comment on the glomerular filtration barrier, with
      a focus on the early aetiopathogenesis of diabetes.

PMID- 27887727
TI  - Shear-mediated platelet activation in the free flow: Perspectives on the emerging
      spectrum of cell mechanobiological mechanisms mediating cardiovascular implant
      thrombosis.
AB  - Shear-mediated platelet activation (SMPA) is central in thrombosis of implantable
      cardiovascular therapeutic devices. Despite the morbidity and mortality
      associated with thrombosis of these devices, our understanding of mechanisms
      operative in SMPA, particularly in free flowing blood, remains limited. Herein we
      present and discuss a range of emerging mechanisms for consideration for "free
      flow" activation under supraphysiologic shear. Further definition and
      manipulation of these mechanisms will afford opportunities for novel
      pharmacologic and mechanical strategies to limit SMPA and enhance overall implant
      device safety.

PMID- 27887728
TI  - Novel multi-functional fluid flow device for studying cellular
      mechanotransduction.
AB  - Cells respond to their mechanical environment by initiating multiple
      mechanotransduction signaling pathways. Defects in mechanotransduction have been
      implicated in a number of pathologies; thus, there is need for convenient and
      efficient methods for studying the mechanisms underlying these processes. A
      widely used and accepted technique for mechanically stimulating cells in culture
      is the introduction of fluid flow on cell monolayers. Here, we describe a novel,
      multifunctional fluid flow device for exposing cells to fluid flow in culture.
      This device integrates with common lab equipment including routine cell culture
      plates and peristaltic pumps. Further, it allows the fluid flow treated cells to
      be examined with outcomes at the cell and molecular level. We validated the
      device using the biologic response of cultured UMR-106 osteoblast-like cells in
      comparison to a commercially available system of laminar sheer stress to track
      live cell calcium influx in response to fluid flow. In addition, we demonstrate
      the fluid flow-dependent activation of phospho-ERK in these cells, consistent
      with the findings in other fluid flow devices. This device provides a low cost,
      multi-functional alternative to currently available systems, while still
      providing the ability to generate physiologically relevant conditions for
      studying processes involved in mechanotransduction in vitro.

PMID- 27887729
TI  - Valveless pumping mechanics of the embryonic heart during cardiac looping:
      Pressure and flow through micro-PIV.
AB  - Cardiovascular development is influenced by the flow-induced stress environment
      originating from cardiac biomechanics. To characterize the stress environment, it
      is necessary to quantify flow and pressure. Here, we quantify the flow field in a
      developing zebrafish heart during the looping stage through micro-particle
      imaging velocimetry and by analyzing spatiotemporal plots. We further build upon
      previous methods to noninvasively quantify the pressure field at a low Reynolds
      number using flow field data for the first time, while also comparing the impact
      of viscosity models. Through this method, we show that the atrium builds up
      pressure to ~0.25mmHg relative to the ventricle during atrial systole and that
      atrial expansion creates a pressure difference of ~0.15mmHg across the atrium,
      resulting in efficient cardiac pumping. With these techniques, it is possible to
      noninvasively fully characterize hemodynamics during heart development.

PMID- 27887730
TI  - Reducing upper airway collapse at lower continuous positive airway titration
      pressure.
AB  - During respiration, upper airway (UA) collapse occurs when the forces generated
      from the negative UA pressures exceed the forces produced by the UA muscles;
      which leads to loose soft tissue at the back of the mouth. At predetermined
      titration pressure, the Continuous Positive Airway Pressure (CPAP) normally
      provides a continuous pressurized and humidified air to prevent airway collapse.
      However, high titration pressures are not always tolerated by patients and may
      lead to damaging effects including stroke symptoms for cardiovascular disease
      patients. This paper hypothesizes that superimposed pressure oscillation can
      modulate the loose tissue and allow unblocking the upper airway passages to help
      reduce the required titration pressure. Using MRI scans, this paper investigates
      the effects of using pressure oscillations superimposed on the CPAP to keep the
      airway open at lower pressure distributions inside the upper airway and
      consequently increase the patients' comfort and reduce their rejection to the
      CPAP.

PMID- 27887731
TI  - Assessment of heavy metal pollution in surface sediments of the Bayan Lepas area,
      Penang, Malaysia.
AB  - This study aimed to evaluate the spatial and temporal distribution of heavy
      metals (Cd, Cr, Cu, Co, Fe, Pb, Ni, V, and Zn) in the sediments of Bayan Lepas
      Free Industrial Zone of Penang, Malaysia. Ten sampling stations were selected and
      sediment samples were collected during low tide (2012-2013). Metals were analyzed
      and the spatial distribution of metals were evaluated based on GIS mapping.
      According to interim sediment quality guidelines (ISQG), metal contents ranged
      from below low level to above high level at different stations. Based on the
      geoaccumulation index (Igeo) of sediment, sampling stations were categorized from
      unpolluted to strongly polluted. The enrichment factor (EF) of metals in the
      sediment varied between no enrichment to extremely high enrichment. The potential
      ecological risk index (RI) indicated Bayan Lepas FIZ was at low risk.

PMID- 27887732
TI  - Expressions of pathologic markers in PRP based chondrogenic differentiation of
      human adipose derived stem cells.
AB  - BACKGROUND: Optimization of the differentiation medium through using autologous
      factors such as PRP is of great consideration, but due to the complex, variable
      and undefined composition of PRP on one hand and lack of control over the
      absolute regulatory mechanisms in in vitro conditions or disrupted and different
      mechanisms in diseased tissue microenvironments in in vivo conditions on the
      other hand, it is complicated and rather unpredictable to get the desired effects
      of PRP making it inevitable to monitor the possible pathologic or undesired
      differentiation pathways and therapeutic effects of PRP. Therefore, in this study
      the probable potential of PRP on inducing calcification, inflammation and
      angiogenesis in chondrogenically-differentiated cells was investigated. METHODS:
      The expressions of chondrogenic, inflammatory, osteogenic and angiogenic markers
      from TGFbeta or PRP-treated cells during chondrogenic differentiation of human
      adipose-derived stem cells (ADSCs) was evaluated. Expressions of Collagen II (Col
      II), Aggrecan, Sox9 and Runx2 were quantified using q-RT PCR. Expression of Col
      II and X was investigated by immunocytochemistry as well. Glycosaminoglycans
      (GAGs) production was also determined by GAG assay. Possible
      angiogenic/inflammatory potential was determined by quantitatively measuring the
      secreted VEGF, TNFalpha and phosphorylated VEGFR2 via ELISA. In addition, the
      calcification of the construct was monitored by measuring ALP activity and
      calcium deposition. RESULTS: Our data showed that PRP positively induced
      chondrogenesis; meanwhile the secretion of angiogenic and inflammatory markers
      was decreased. VEGFR2 phosphorylation and ALP activity had a decreasing trend,
      but tissue mineralization was enhanced upon treating with PRP. CONCLUSIONS:
      Although reduction in inflammatory/angiogenic potential of the chondrogenically
      differentiated constructs highlights the superior effectiveness of PRP in
      comparison to TGFbeta for chondrogenic differentiation, yet further improvement
      of the PRP-based chondrogenic differentiation media is required to inhibit the
      production of angiogenic/inflammatory markers, calcification and the release of
      synthesized GAG out of the construct.

PMID- 27887733
TI  - Determining oxidative stress and EROD activity in dab (Limanda limanda) in the
      North and Baltic Seas.
AB  - The North and Baltic Seas are heavily trafficked marine areas with extensive
      anthropogenic activities, including cargo and fishing vessels, waste dumping, oil
      platforms, industrial activities and contamination from coastal runoff. In order
      to evaluate the environmental health of these regions, we used the demersal fish
      dab (Limanda limanda) as a sentinel species. The current study used well
      established biomarkers for PAH exposure and oxidative stress, measuring EROD
      activity, the acute antioxidant response as well as oxidation of proteins
      detected as protein carbonyl levels. Results show the strongest biomarker results
      in an area with extensive oil drilling, where dab displayed high levels of EROD
      activities. This was also seen in dab captured in the Baltic Sea where elevated
      levels of oxidized glutathione and a trend towards higher EROD activity were
      observed. The obtained results did, however, not indicate a coherent biomarker
      response. The study was conducted off shore where many areas have presumably low
      levels of pollutants, and we could detect minor effects using the biomarker
      approach.

PMID- 27887734
TI  - Two countries - Two treatment strategies for rectal cancer.
AB  - BACKGROUND AND PURPOSE: Trials in rectal cancer have shown that radiotherapy (RT)
      decreases local recurrence rates, whereas the effects on survival are uncertain.
      Swedish and Norwegian oncologists have had different treatment recommendations.
      The aim was to evaluate local recurrence rates and survival in the two countries.
      PATIENTS AND METHODS: Between 1995 and 2012 rectal cancer patients registered in
      Sweden and Norway were analyzed, presenting population-based "real world" data.
      RESULTS: Totally 29,029 Swedish and 15,456 Norwegian patients were analyzed.
      Resection for cure was performed in two-thirds of the patients. RT was given to
      49% of Swedish patients, mainly short-course RT and to 26% of Norwegian patients,
      predominantly chemoradiotherapy (CRT). In Sweden, the proportion irradiated was
      stable whereas in Norway, an increase from 10% to 40% was seen. Local 5-year
      recurrence rates were initially higher in Norway (12%) than in Sweden (8%),
      whereas they were equally low (4%) during the latter time. No survival
      differences were seen, however, survival improved with time in both countries.
      CONCLUSIONS: Two entirely different approaches to preoperative therapy resulted
      in similar survival with initially higher local recurrence rates in Norway, but
      similarly low rates in later years. This raises questions about optimal RT rates
      and regimens.

PMID- 27887735
TI  - Influence of general anaesthesia on the brainstem.
AB  - The exact role of the brainstem in the control of body functions is not yet well
      known and the same applies to the influence of general anaesthesia on brainstem
      functions. Nevertheless in all general anaesthesia the anaesthesiologist should
      be aware of the interaction of anaesthetic drugs and brainstem function in
      relation to whole body homeostasis. As a result of this interaction there will be
      changes in consciousness, protective reflexes, breathing pattern, heart rate,
      temperature or arterial blood pressure to name a few. Brainstem function can be
      explored using three different approaches: clinically, analyzing changes in brain
      electric activity or using neuroimaging techniques. With the aim of providing the
      clinician anaesthesiologist with a global view of the interaction between the
      anaesthetic state and homeostatic changes related to brainstem function, the
      present review article addresses the influence of anaesthetic drug effects on
      brainstem function through clinical exploration of cranial nerves and reflexes,
      analysis of electric signals such as electroencephalographic changes and what it
      is known about brainstem through the use of imaging techniques, more specifically
      functional magnetic resonance imaging.

PMID- 27887736
TI  - Use of Clarus Video System(r) in expected difficult airway in a patient with Rett
      syndrome.
AB  - Difficult airway management remains one of the key points in our specialty, as
      the difficulty or impossibility of tracheal intubation is the main cause of
      morbidity/mortality attributable to anaesthesia. Rett syndrome is a severe and
      incapacitating neurological disease. We present the case of a 21-year-old girl
      affected by this syndrome, with significant psychomotor retardation and difficult
      airway predictors, who was scheduled to have a laparoscopic cholecystectomy under
      general anaesthesia. We decided on one attempt of Clarus Video System(r)
      fiberoptic intubation as primary intervention. Intubation was successfully
      performed with the help of this optical stylet. The use of optical stylets is
      gaining prominence and finding a place in the latest algorithms of difficult
      airway management. We highlight the growing role these devices play in managing
      difficult airway, therefore we review the current situation of videolaryngoscopes
      in the management of the predicted difficult airway.

PMID- 27887737
TI  - Polyphenolic diversity and characterization in the red-purple berries of East
      Asian wild Vitis species.
AB  - Grapes (Vitis spp.) produce diverse polyphenolic compounds, which are
      phytochemicals that contribute to human health. In this study, the polyphenolic
      profiles of the red-purple berries of two wild grape species native to Japan,
      Vitis ficifolia and V. coignetiae, and their interspecific hybrid cultivars were
      investigated and compared with the profiles of V. vinifera and V. * labruscana
      cultivars. Proanthocyanidins (PAs) were present at lower concentrations in both
      skins and seeds of wild grape species and their hybrid cultivars than those in V.
      vinifera cultivars. They also differed in their composition, consisting mainly of
      epicatechin in wild grape species, but containing considerable amounts of both
      epigallocatechin in the skins and epicatechin gallate in the seeds of V.
      vinifera. In contrast, V. ficifolia varieties and their hybrid cultivars
      accumulated high concentrations of diverse anthocyanins, and whose compositions
      of anthocyanins and flavonols differed between species in their degree of
      modification by glucosylation, acylation, methylation and B-ring hydroxylation.
      Principal component analysis (PCA) indicated that the polyphenolic constituents
      clearly separate V. vinifera and V. * labruscana cultivars from the wild grape
      species as well as between wild grape species, V. coignetiae and V. ficifolia.
      Intermediate compositions were also observed in the hybrid cultivars between
      these wild grape species and V. vinifera.

PMID- 27887738
TI  - Mother-infant interactions in captive and wild chimpanzees.
AB  - We review studies on mother-infant interactions in chimpanzees, our closest
      living relatives, in captive and wild environments. Infant cognitive development
      is formed through mother-infant interactions during the long dependent period,
      which is approximately 5 years. Patterns of interaction between mothers and
      infants are different from those observed in adult chimpanzees. Mother-infant
      interactions are relatively altruistic, although solicitation by infants is
      almost always required. Active teaching has rarely been reported in chimpanzees;
      instead, infants socially learn new skills through long-term observation. Case
      studies describing rearing of a disabled infant by a multiparous but
      inexperienced chimpanzee, and the carrying of dead infants in the wild
      chimpanzees of Bossou reveal the strong affectionate bond between mothers and
      infants. Characteristics of human mother-infant interaction are highlighted
      through comparisons with chimpanzees.

PMID- 27887739
TI  - Differences in the modulation of reactive species, lipid bodies, cyclooxygenase
      2, 5-lipoxygenase and PPAR-gamma in cerebral malaria-susceptible and resistant
      mice.
AB  - Proinflammatory responses are associated with the severity of cerebral malaria.
      NO, H2O2, eicosanoid and PPAR-gamma are involved in proinflammatory responses,
      but regulation of these factors is unclear in malaria. This work aimed to compare
      the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible CBA
      and C57BL/6 and -resistant BALB/c mice. Mice were infected with Plasmodium
      berghei ANKA, and the survival rates and parasitemia curves were assessed. On the
      sixth day post-infection, cyclooxygenase-2 and 5-lipoxygenase in brain sections
      were assessed by immunohistochemistry, and, NO, H2O2, lipid bodies, and PPAR
      gamma expression were assessed in peritoneal macrophages. The C57BL/6 had more
      severe disease with a lower survival time, higher parasitemia and lower
      production of plasmodicidal NO and H2O2 molecules than BALB/c. Enhanced COX-2 and
      5-LOX expression were observed in brain tissue cells and vessels from C57BL/6
      mice, and these mice expressed higher constitutive PPAR-gamma levels. There was
      no translocation of PPAR-gamma from cytoplasm to nucleus in macrophages from
      these mice. CBA mice had enhanced COX-2 expression in brain tissue cells and
      vessels and also lacked PPAR-gamma cytoplasm-to-nucleus translocation. The
      resistant BALB/c mice presented higher survival time, lower parasitemia and
      higher NO and H2O2 production on the sixth day post-infection. These mice did not
      express either COX-2 or 5-LOX in brain tissue cells and vessels. Our data showed
      that besides the high parasite burden and lack of microbicidal molecules, an
      imbalance with high COX-2 and 5-LOX eicosanoid expression and a lack of
      regulatory PPAR-gamma cytoplasm-to-nucleus translocation in macrophages were
      observed in mice that develop cerebral malaria.

PMID- 27887740
TI  - Outcomes of Renal Transplantation in Patients With Bipolar Affective Disorder and
      Schizophrenia: A National Retrospective Cohort Study.
AB  - BACKGROUND: Patients with severe psychiatric disorders such as schizophrenia and
      bipolar affective disorder (BPAD) have in the past been excluded from organ
      transplantation programs based on their psychiatric illness. However, there is
      little data on the outcomes of renal transplantation in these patients and little
      evidence to support such exclusion. METHODS: We reviewed the database of the
      Irish National Renal Transplant Programme and identified all patients with a
      history of BPAD or schizophrenia who had received a transplant over a 28-year
      period. Data were collected for the following outcomes: patient survival, graft
      survival, graft function, length of hospitalization for transplantation, and
      frequency of acute rejection episodes. The control group was the general
      transplant group, that is, all patients without these psychiatric disorders and
      who had received a renal transplant during the relevant time period. RESULTS:
      Between January 1, 1986, and December 31, 2013, 3000 renal transplants were
      performed at our center. Of the transplant recipients, 0.5% (n = 15) had a
      diagnosis of BPAD and 0.2% (n = 6) had schizophrenia. No significant differences
      were found between the BPAD or schizophrenia group and the general renal
      transplant group in relation to patient survival, graft survival, and graft
      function. In addition, length of hospital admission for transplantation and
      frequency of acute rejection episodes were comparable among the 3 groups.
      CONCLUSIONS: Although consideration of psychiatric comorbidity is an important
      part of pretransplant assessment and selection, patients should not be
      discriminated against based on a diagnosis of BPAD or schizophrenia as there is
      no evidence that this negatively affects transplant outcomes.

PMID- 27887741
TI  - Evaluation of 16 genotype-guided Warfarin Dosing Algorithms in 310 Korean
      Patients Receiving Warfarin Treatment: Poor Prediction Performance in VKORC1
      1173C Carriers.
AB  - PURPOSE: The purpose of this study was to evaluate the performance of 16
      previously published warfarin dosing algorithms in Korean patients. METHODS: The
      16 algorithms were selected through a literature search and evaluated using a
      cohort of 310 Korean patients with atrial fibrillation or cerebral infarction who
      were receiving warfarin therapy. FINDINGS: A large interindividual variation (up
      to 11-fold) in warfarin dose was observed (median, 25 mg/wk; range, 7-77 mg/wk).
      Estimated dose and actual maintenance dose correlated well overall (r range, 0.52
      0.73). Mean absolute error (MAE) of the 16 algorithms ranged from -1.2 to -20.1
      mg/wk. The percentage of patients whose estimated dose fell within 20% of the
      actual dose ranged from 1.0% to 49%. All algorithms showed poor accuracy with
      increased MAE in a higher dose range. Performance of the dosing algorithms was
      worse in patients with VKORC1 1173TC or CC than in total (r range, 0.38-0.61 vs
      0.52-0.73; MAE range, -2.6 to -28.0 mg/wk vs -1.2 to -20.1 mg/wk). IMPLICATIONS:
      The algorithms had comparable prediction abilities but showed limited accuracy
      depending on ethnicity, warfarin dose, and VKORC1 genotype. Further studies are
      needed to develop genotype-guided warfarin dosing algorithms with greater
      accuracy in the Korean population.

PMID- 27887742
TI  - Corrigendum to "Dentognathic remains of Australopithecus afarensis from Nefuraytu
      (Woranso-Mille, Ethiopia): Comparative description, geology, and paleoecological
      context" [J Hum Evol 100 (2016) 35-53].

PMID- 27887743
TI  - Quantification of Diabetic Macular Ischemia Using Optical Coherence Tomography
      Angiography and Its Relationship with Visual Acuity.
AB  - PURPOSE: To quantify foveal avascular zone (FAZ) area and macular vascular
      density objectively using optical coherence tomography angiography (OCTA) and to
      examine correlations with visual acuity in eyes with diabetic retinopathy (DR) in
      the absence of diabetic macular edema. DESIGN: Retrospective observational case
      series. PARTICIPANTS: Eighty-four eyes from 55 patients with DR and 34 control
      eyes from 27 age-matched healthy participants. METHODS: All eyes underwent OCTA
      (RTVue-XR Avanti; Optovue, Inc, Fremont, CA). Integrated automated algorithms
      were used to quantify FAZ area and macular vascular density. MAIN OUTCOME
      MEASURES: FAZ area, vessel area density (VAD), vessel length density (VLD), and
      visual acuity. RESULTS: In each study eye, DR was classified as mild
      nonproliferative DR (NPDR; n = 32 [38%]), moderate-to-severe NPDR (n = 31 [37%]),
      or proliferative DR (n = 21 [25%]). Mean FAZ area was greater in diabetic eyes
      compared with control eyes both in the superficial (0.427 mm2 vs. 0.275 mm2; P <
      0.001) and deep (0.616 mm2 vs. 0.372 mm2; P < 0.001) vascular networks. Mean VAD
      was lower in diabetic eyes compared with control eyes in both the superficial
      (49.44% vs. 55.09%; P < 0.001) and deep (56.65% vs. 61.32%; P < 0.001) networks.
      Mean VLD was also lower in diabetic eyes compared with control eyes in both the
      superficial (17.68 mm-1 vs. 21.55 mm-1; P < 0.001) and deep (21.19 mm-1 vs. 24.38
      mm-1; P < 0.001) networks. In all eyes, there was a statistically significant
      negative correlation between the logarithm of the minimum angle of resolution
      (logMAR) visual acuity and the vascular density in both the superficial (VAD, rho
      = -0.52; VLD, rho = -0.54; P < 0.001) and deep (VAD, rho = -0.50; VLD, rho = 
      0.50; P < 0.001) networks. A positive correlation was found between logMAR visual
      acuity and FAZ area in both the superficial (rho = 0.29; P < 0.01) and deep (rho
      = 0.48; P < 0.001) networks. CONCLUSIONS: Automated quantitative algorithms allow
      for objective assessment of retinal vascular changes in eyes with DR that are
      correlated to visual acuity. These methods may prove useful in monitoring disease
      progression and identifying parameters that affect visual function.

PMID- 27887744
TI  - Findings from a UK-Morocco training programme to improve capacity in nutrition
      surveillance, research and education.

PMID- 27887745
TI  - 2016 Pinnochio awards: Public Health Responsibility Deal among the nominees!

PMID- 27887746
TI  - Behaviour revised: Contaminant effects on aquatic animal behaviour.

PMID- 27887747
TI  - The Rise of Invasive Species Denialism.
AB  - Scientific consensus on the negative impacts of invasive alien species (IAS) is
      increasingly being challenged. Whereas informed scepticism of impacts is
      important, science denialism is counterproductive. Such denialism arises when
      uncertainty on impacts is confounded by differences in values. Debates on impacts
      must take into account both the evidence presented and motivations.

PMID- 27887748
TI  - Probes for manipulating and monitoring IP3.
AB  - Inositol 1,4,5-trisphosphate (IP3) is an important second messenger produced via
      G-protein-coupled receptor- or receptor tyrosine kinase-mediated pathways. IP3
      levels induce Ca2+ release from the endoplasmic reticulum (ER) via IP3 receptor
      (IP3R) located in the ER membrane. The resultant spatiotemporal pattern of Ca2+
      signals regulates diverse cellular functions, including fertilization, gene
      expression, synaptic plasticity, and cell death. Therefore, monitoring and
      manipulating IP3 levels is important to elucidate not only the functions of IP3
      mediated pathways but also the encoding mechanism of IP3R as a converter of
      intracellular signals from IP3 to Ca2+.

PMID- 27887749
TI  - Angiogenic factors are associated with multiple sclerosis.
AB  - A growing body of evidence suggests that angiogenesis plays a crucial role in the
      pathogenesis of multiple sclerosis (MS). Animal models of MS show a significant
      improvement when the process of angiogenesis is halted. In this study, we
      measured the serum levels of vascular-endothelial growth factor (VEGF), soluble
      Endoglin (sEng), angiopoietin 1(Ang-1), angiopoietin 2 (Ang-2), and uric acid
      (UA) as well as serum anti-Epstein-Barr virus (EBV) EBNA-1 IgG in 50 MS patients
      (including 20 newly diagnosed and 30 patients taking IFN-beta for >6months) and
      40 healthy individuals. Enzyme-linked immunosorbent assays (ELISA) were used
      apart from UA where the uricase quantitative enzymatic assay was used. A
      significant increase of VEGF, Ang-1, Ang-2, and sEng in serum samples of MS
      patients with respect to healthy subjects was observed. VEGF was higher in newly
      diagnosed MS patients in comparison to patients taking interferon-beta and was
      associated with EDSS. The serum levels of UA were statistically lower in MS
      patients as compared to the healthy group. Higher levels of anti-EBV antibody
      titers were seen in MS patients than controls and anti-EBV titers correlated with
      angiogenic factors. It seems that in summary, angiogenesis may play an important
      role in MS and infection with EBV might be correlated with this phenomenon.

PMID- 27887750
TI  - Chronic Kidney Disease.
AB  - The definition and classification of chronic kidney disease (CKD) have evolved
      over time, but current international guidelines define this condition as
      decreased kidney function shown by glomerular filtration rate (GFR) of less than
      60 mL/min per 1.73 m2, or markers of kidney damage, or both, of at least 3 months
      duration, regardless of the underlying cause. Diabetes and hypertension are the
      main causes of CKD in all high-income and middle-income countries, and also in
      many low-income countries. Incidence, prevalence, and progression of CKD also
      vary within countries by ethnicity and social determinants of health, possibly
      through epigenetic influence. Many people are asymptomatic or have non-specific
      symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made
      after chance findings from screening tests (urinary dipstick or blood tests), or
      when symptoms become severe. The best available indicator of overall kidney
      function is GFR, which is measured either via exogenous markers (eg, DTPA,
      iohexol), or estimated using equations. Presence of proteinuria is associated
      with increased risk of progression of CKD and death. Kidney biopsy samples can
      show definitive evidence of CKD, through common changes such as glomerular
      sclerosis, tubular atrophy, and interstitial fibrosis. Complications include
      anaemia due to reduced production of erythropoietin by the kidney; reduced red
      blood cell survival and iron deficiency; and mineral bone disease caused by
      disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five
      to ten times more likely to die prematurely than they are to progress to end
      stage kidney disease. This increased risk of death rises exponentially as kidney
      function worsens and is largely attributable to death from cardiovascular
      disease, although cancer incidence and mortality are also increased. Health
      related quality of life is substantially lower for people with CKD than for the
      general population, and falls as GFR declines. Interventions targeting specific
      symptoms, or aimed at supporting educational or lifestyle considerations, make a
      positive difference to people living with CKD. Inequity in access to services for
      this disease disproportionally affects disadvantaged populations, and health
      service provision to incentivise early intervention over provision of care only
      for advanced CKD is still evolving in many countries.

PMID- 27887751
TI  - Heart failure and vitamin D receptor gene.

PMID- 27887752
TI  - Changes in plasma fatty acid composition are associated with improvements in
      obesity and related metabolic disorders: A therapeutic approach to overweight
      adolescents.
AB  - BACKGROUND & AIMS: In recent years, obesity has reached alarming levels among
      children and adolescents. The study of plasma fatty acid (FA) composition, as a
      reflection of diet, and its associations with other parameters, that are closely
      linked to obesity and the cardiometabolic profile, may be useful for setting
      nutritional goals for obesity treatment and prevention. This study explored the
      relationship between plasma FA levels and body fat and cardiometabolic risk
      markers, in overweight adolescents. METHODS: A multidisciplinary weight loss
      program was followed by 127 overweight and obese adolescents aged 12-17 years
      old. Plasma FA composition, anthropometric indicators of adiposity and
      biochemical parameters were analyzed at baseline, two months (the end of the
      intensive intervention phase) and six months (the end of the extensive phase).
      RESULTS: While saturated fatty acid (SFA) and n-6 polyunsaturated fatty acid
      (PUFA) levels decreased significantly during the intervention, monounsaturated
      fatty acid (MUFA) and n-3 PUFA showed the opposite trend. The decrease in SFA
      C14:0 was associated with a reduction in total and LDL cholesterol,
      apolipoprotein B and insulin. The increase in MUFAs, especially C18:1n-9, was
      related to a reduction in weight, fat mass, fat mass index and glucose. Regarding
      PUFAs, changes in the n-3 series were not associated with any of the parameters
      studied, whereas the reduction in n-6 PUFAs was directly related to weight, fat
      mass, total and HDL cholesterol, apolipoprotein A1, glucose and insulin, and
      inversely associated with diastolic blood pressure. The adolescents with greater
      weight loss presented significant changes in MUFAs, n-6 PUFAs and C14:0.
      CONCLUSIONS: Modifications in plasma FA composition were associated with
      adiposity reduction and cardiometabolic profile improvement in an anti-obesity
      program aimed at adolescents. The changes observed in FA composition were related
      to the success of the treatment, since the individuals most affected by these
      variations were those who presented the greatest weight loss.

PMID- 27887753
TI  - Effect of culturally competent educational films about prenatal screening on
      informed decision making of pregnant women in the Netherlands.
AB  - OBJECTIVE: To evaluate the effect of a culturally competent educational film
      (CCEF) on informed decision making (IDM) regarding prenatal screening (PS) in a
      study population consisting of multicultural pregnant women. METHODS: A cross
      sectional study with 262 women in the control group and 117 in the intervention
      group. All counselled participants received a self-report questionnaire to obtain
      data on IDM and only the intervention group received the CCEF. Twenty two percent
      of the study population had an ethnic minority background and 52% had a low or
      medium educational level. RESULTS: After exposure to the CCEF, knowledge about
      the Fetal Anomaly Scan (FAS) was significantly increased in ethnic minority women
      and in 'medium' and 'highly' educated women. Among women in the intervention
      group who had the intention to participate in FAS, there was an increase of 11%
      in IDM and a decrease of 12% in uninformed decision making. CONCLUSION: CCEF
      leads to a significant increase in the level of knowledge in medium and highly
      educated groups as well as non-western ethnic minority groups. The increase in
      IDM among intentional participants in the FAS is promising as well. CCEF's are a
      valuable complement to counseling about PS.

PMID- 27887756
TI  - Needlestick injuries among healthcare professionals in training: using the
      surgical 'time-out' and hand-off protocols to deter high-risk needlesticks.

PMID- 27887754
TI  - Meticillin-resistant Staphylococcus aureus (MRSA) acquisition risk in an endemic
      neonatal intensive care unit with an active surveillance culture and
      decolonization programme.
AB  - BACKGROUND: Meticillin-resistant Staphylococcus aureus (MRSA) is a leading cause
      of healthcare-associated infection in the neonatal intensive care unit (NICU).
      Decolonization may eliminate bacterial reservoirs that drive MRSA transmission.
      AIM: To measure the association between colonization pressure from decolonized
      and non-decolonized neonates and MRSA acquisition to inform use of this strategy
      for control of endemic MRSA. METHODS: An eight-year retrospective cohort study
      was conducted in a level-4 NICU that used active surveillance cultures and
      decolonization for MRSA control. Weekly colonization pressure exposures were
      defined as the number of patient-days of concurrent admission with treated
      (decolonized) and untreated (non-decolonized) MRSA carriers in the preceding
      seven days. Poisson regression was used to estimate risk of incident MRSA
      colonization associated with colonization pressure exposures. The population
      attributable fraction was calculated to assess the proportion of overall unit
      MRSA incidence attributable to treated or untreated patients in this setting.
      FINDINGS: Every person-day increase in exposure to an untreated MRSA carrier was
      associated with a 6% increase in MRSA acquisition risk [relative risk (RR): 1.06;
      95% confidence interval (CI): 1.01-1.11]. Risk of acquisition was not influenced
      by exposure to treated, isolated MRSA carriers (RR: 1.01; 95% CI: 0.98-1.04). In
      the context of this MRSA control programme, 22% (95% CI: 4.0-37) of MRSA
      acquisition could be attributed to exposures to untreated MRSA carriers.
      CONCLUSION: Untreated MRSA carriers were an important reservoir for transmission.
      Decolonized patients on contact isolation posed no detectable transmission
      threat, supporting the hypothesis that decolonization may reduce patient-to
      patient transmission. Non-patient reservoirs may contribute to unit MRSA
      acquisition and require further investigation.

PMID- 27887755
TI  - Use of ventilator utilization ratio for stratifying alcohol-based hand-rub
      consumption data to improve surveillance on intensive care units.
AB  - BACKGROUND: Germany has established a nationwide surveillance system of alcohol
      based hand-rub consumption (AHC) per patient-day in hospital settings as a
      surrogate parameter for hand hygiene (HH) compliance. Analysis of AHC data in
      intensive care units (ICUs) shows not only a wide range of consumption between
      units of different specialties, but also within units of one specialty. This
      seems to reflect variation in the number of HH opportunities per patient-day
      between ICUs due to variation in complexity of care. AIM: To investigate whether
      ventilator utilization ratio (VUR) might be a good surrogate for describing
      complexity and intensity of care on ICUs and whether stratification by VUR works
      as a new method of setting benchmarks for AHC data. METHODS: Data from 365 ICUs
      participating in the German national nosocomial infection surveillance system
      (KISS) were used. VUR was calculated by dividing the number of ventilator-days
      per unit by the number of patient-days per unit. AHC was stratified according to
      VUR in quartiles. FINDINGS: The median AHC was 107mL/patient-day [interquartile
      range (IQR): 86-134] and the median VUR was 33% (IQR: 22-45%). The Spearman rank
      correlation coefficient was 0.28 (P<0.0001). After stratifying AHC according to
      VUR, the AHC in quartile I was significantly lower compared to quartile IV. There
      was also significant difference between quartile I and quartiles II and III.
      CONCLUSION: Stratification of AHC data according to VUR is suggested to improve
      the quality of benchmark parameters based on AHC data as surrogate parameter for
      HH compliance in ICUs.

PMID- 27887757
TI  - Hepatic Artery Rupture in a Young Man with Abdominal Pain and a Testicular Mass.
AB  - BACKGROUND: Male patients presenting to the emergency department (ED) with
      abdominal pain accompanied by a testicular mass should be evaluated for the
      presence of hernia, epididymitis, orchitis, and testicular torsion. When a
      patient presents with an asymptomatic testicular nodule or mass, the emergency
      physician should consider testicular carcinoma, a diagnosis that typically
      warrants no more than prompt urologic outpatient referral. CASE REPORT: We
      present a case involving a young male whose presenting complaint was abdominal
      pain. Despite his reluctance to initially discuss any genitourinary (GU)
      complaints, careful questioning and thorough examination revealed a large left
      testicular mass. Despite having a benign abdomen, the patient experienced a rapid
      clinical deterioration in the ED after a previously undiagnosed metastatic lesion
      to his liver eroded into his hepatic artery. WHY SHOULD AN EMERGENCY PHYSICIAN BE
      AWARE OF THIS?: This case highlights the importance of performing a GU
      examination in all patients presenting with abdominal pain and discusses a rare
      presentation of a relatively common male condition. We also discuss the
      prioritization of emergent interventions and diagnostic studies specific to this
      case.

PMID- 27887758
TI  - Blind Nasal Intubation Revisited: No Longer a Blind Technique?
AB  - BACKGROUND: Advancements in airway management have made the practice of blind
      nasal intubation obsolete. We report on successful blind nasal intubation
      performed with the help of capnography and real-time ultrasonography in two
      patients with tempormandibular joint ankylosis. CASE REPORT: Blind nasal
      intubation was performed in a 12-year-old patient and a 17-year old patient under
      general anesthesia with spontaneous respiration. Capnography was used as an aid
      during insertion and dynamic ultrasonography was performed to guide and confirm
      proper tracheal tube placement. Use of capnography helps in following the correct
      path toward the glottic opening, with quick detection of any obstruction, and
      with confirmation of final placement of the tracheal tube. Ultrasonography aids
      with entry into the glottis and with identifying the correct placement. We
      recommend the use of this modified blind nasal intubation in patients with
      limited mouth opening when equipment, such as a fiberoptic scope, is not
      available or is nonfunctional in the emergency department. WHY SHOULD AN
      EMERGENCY PHYSICIAN BE AWARE OF THIS?: Adapting this technique will add to the
      armamentarium available for airway management in emergency medicine, particularly
      in maxillofacial injuries with limited mouth opening.

PMID- 27887759
TI  - Implementing an open-access CASA software for the assessment of stallion sperm
      motility: Relationship with other sperm quality parameters.
AB  - Setting an open-access computer assisted sperm analysis (CASA) may benefit the
      evaluation of motility in mammalian sperm, especially when economic constraints
      do not allow the use of a commercial system. There have been successful attempts
      to develop such a device in Zebra fish sperm and the system has been used in very
      few studies on mammalian spermatozoa. Against this background, the present study
      aimed at developing an open-access CASA system for mammalian sperm using the
      horse as a model and based upon the Image J software previously established for
      Zebra fish sperm. Along with determining the sperm progressive motility and other
      kinetic parameters (such as amplitude of lateral head displacement), the
      "results" window was adjusted to simplify subsequent statistical analyses. The
      path window was enriched with colored sperm trajectories on the basis of the
      subpopulation they belong to and a number that allowed the sperm track to be
      associated to the sperm motility data shown in the "results" window. Data
      obtained from the novel plugin (named as CASA_bgm) were compared with those of
      the commercial CASA Hamilton-Thorn IVOS Vers.12, through Bland Altman's plots.
      While the percentage of total and progressive motile sperm, VCL, VAP, VSL, LIN
      and STR and ALH were in agreement with those obtained with the commercial system,
      BCF significantly differed between the two systems probably due to their
      settings. Interestingly, a positive and significant correlation between the
      percentages of total motile sperm evaluated through CASA_bgm and those showing
      high mitochondrial membrane potential evaluated by JC-1 staining was found. In
      conclusion, CASA_bgm ImageJ plugin could be useful and reliable for stallion
      sperm motility analysis and it is our aim to apply this system to other mammalian
      species.

PMID- 27887760
TI  - Response by Wallace et al. to letter regarding "Quadrigeminal Perimesencephalic
      Subarachnoid Hemorrhage".

PMID- 27887761
TI  - Letter to the Editor regarding "Quadrigeminal Perimesencephalic Subarachnoid
      Hemorrhage".

PMID- 27887762
TI  - Extracardiac Signs of Fluid Overload in the Critically Ill Cardiac Patient: A
      Focused Evaluation Using Bedside Ultrasound.
AB  - Fluid balance management is of great importance in the critically ill cardiac
      patient. Although intravenous fluids are a cornerstone therapy in the management
      of unstable patients, excessive administration coupled with cardiac dysfunction
      leads to elevation in central venous pressure and end-organ venous congestion.
      Fluid overload is known to have a detrimental effect on organ function and is
      responsible for significant morbidity in critically ill patients. Multisystem
      bedside point of care ultrasound imaging can be used to assess signs of fluid
      overload and venous congestion in critically ill patients. In this review we
      describe the ultrasonographic extracardiac signs of fluid overload and how they
      can be used to complement clinical evaluation to individualize patient
      management.

PMID- 27887763
TI  - Composite lymphoma with diffuse large B-cell lymphoma and classical Hodgkin
      lymphoma components: A case report and review of the literature.
AB  - Composite lymphoma (CL) is an infrequently diagnosed entity in which two or more
      distinct types of lymphomas occur synchronously in the same organ or anatomical
      site. Most commonly, CLs are composed of two non-Hodgkin B-cell lymphomas. We
      present a case of a composite lymphoma with diffuse large B-cell lymphoma, not
      otherwise specified (DLBCL-NOS) and classical Hodgkin lymphoma (CHL) components
      involving the terminal ileum, colon and pericolic lymph nodes.
      Immunohistochemical evaluation for determination of cell of origin of the DLBCL
      NOS component indicated a germinal center B-cell subtype. Immunoglobulin heavy
      chain fragment length analysis revealed identical dominant monoclonal peaks on
      the DH1-6-JH reaction, and also a dominant monoclonal peak observed only in the
      framework II reaction done on the CHL component, indicating a partial clonal
      relationship between the two components. Additionally, a review of the available
      literature reveals a total of 20 previously reported cases of CL with DLBCL-NOS
      and CHL components, and most of the tested cases showed clonal relationship
      between the two components. The overall findings indicate that in most cases, the
      two components of CL with DLBCL-NOS and CHL components are clonally related, and
      suggest a shared origin from a common B-cell precursor.

PMID- 27887764
TI  - The importance of economic context in interpreting forensic data on drug
      trafficking networks.

PMID- 27887765
TI  - Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae
      expressing combined mechanisms of resistance.
AB  - INTRODUCTION: Antimicrobial resistance in Enterobacteriaceae is increasing
      worldwide and is making treating infections caused by multidrug-resistant
      Enterobacteriaceae a challenge. The use of beta-lactam agents is compromised by
      microorganisms harboring extended-spectrum beta-lactamases (ESBLs) and other
      mechanisms of resistance. Avibactam is a non beta-lactam agent that inhibits
      clinically relevant beta-lactamases, such as ESBL and AmpC. The ceftazidime
      avibactam combination (CAZ-AVI) was recently approved for use in certain
      complicated infections, and may provide a therapeutic alternative for infections
      caused by these microorganisms. METHODS: The in vitro activity of CAZ and CAZ-AVI
      (AVI at a fixed concentration of 4mg/L) was tested against 250 clinical isolates
      of Enterobacteriaceae using broth microdilution. EUCAST breakpoint criteria were
      used for CAZ, and FDA criteria for CAZ-AVI. Clinical isolates included bacteria
      producing extended-spectrum beta-lactamases (ESBLs) and acquired AmpC beta
      lactamases (AACBLs). Porin loss in Klebsiella pneumoniae was also evaluated.
      RESULTS: The combination of AVI with CAZ displayed excellent activity against
      clinical isolates of ESBL-producing Escherichia coli and Klebsiella pneumoniae,
      rendering all the ceftazidime-resistant isolates susceptible to ceftazidime. CAZ
      AVI retained activity against porin-deficient isolates of K. pneumoniae producing
      ESBLs, AACBLs, or both, although MIC values were higher compared to porin
      expressing isolates. CAZ-AVI rendered all the ceftazidime-resistant AACBL
      producing Enterobacteriaceae tested susceptible to ceftazidime. CONCLUSION: CAZ
      AVI showed potent in vitro activity against clinical isolates of
      Enterobacteriaceae producing ESBLs and/or AACBLs, including K. pneumoniae with
      loss of porins.

PMID- 27887768
TI  - Evaluation of Acute Kidney Injury Using Contrast Ultrasonography in a Rabbit
      Model of Crush Syndrome.
AB  - This study aimed to investigate the feasibility of evaluating acute kidney injury
      (AKI) using contrast ultrasonography in a rabbit model of crush syndrome. Sixty
      four New Zealand white rabbits were anesthetized and the left hind limb was
      wrapped and compressed for 4 h with a sphygmomanometer. Contrast ultrasonography
      of the left kidney using microbubbles as the contrast medium was performed. The
      serum levels of blood urea nitrogen (BUN), creatine (Cr), creatine kinase (CK)
      and lactate dehydrogenase (LDH) were significantly increased in comparison to
      before the compression. Correlation analysis showed that peak intensity was
      negatively correlated with the biochemical parameters and area under the curve
      (AUC) was positively correlated with these parameters. Contrast ultrasonography
      is thus sensitive to the changes in renal perfusion after limb crush injury in
      rabbits. The ultrasonography results correlated well with the biochemical
      parameters that are related to muscle injury and AKI.

PMID- 27887770
TI  - Robust learning in SpikeProp.
AB  - Training a Spiking Neural Network using SpikeProp and its derivatives faces
      stability issues. Surges, marked by a sudden rise in learning cost, are a common
      occurrence during the learning process. They disrupt the learning process and
      often destabilize the process resulting in failure. A proper learning rate, which
      is neither too small nor too big, is important to minimize surges. Furthermore,
      external disturbances due to imperfection in sample data as well as internal
      disturbances are additional destabilizing source during the learning process. In
      this paper, we perform error system analysis incorporating external disturbance,
      followed by weight convergence analysis along with detailed robust stability
      analysis of SpikeProp learning process to ensure error bound of the learning
      process. Based on these results, we propose a robust adaptive learning rate
      scheme that aligns with the results of theoretical analysis. The performance of
      the proposed method has been compared with other prevalent methods based on
      different benchmark datasets and the results demonstrate that our method indeed
      has better performance in terms of convergence and learning speed as well.

PMID- 27887769
TI  - Activity and Sedentary Time 10 Years After a Successful Lifestyle Intervention:
      The Diabetes Prevention Program.
AB  - INTRODUCTION: This study aims to determine if evidence exists for a lasting
      effect of the Diabetes Prevention Program (DPP) lifestyle intervention on
      activity levels by comparing objectively collected activity data between the DPP
      Outcome Study (DPPOS) cohort and adults from the National Health and Nutrition
      Examination Survey (NHANES; 2003-2006). METHODS: Average minutes/day of light and
      moderate to vigorous physical activity (MVPA) and sedentary behavior from
      ActiGraph accelerometers (collected 2010-2012) were examined (2013-2014) for
      comparable DPPOS and NHANES subgroups by age, sex, and diabetes status.
      Longitudinal questionnaire data on leisure activity, collected yearly from DPP
      baseline to the time of accelerometer measurement (1996-2010; 11.9-year mean
      follow-up), were also examined to provide support for a long-term intervention
      effect. RESULTS: Average minutes/day of accelerometer-derived MVPA was higher in
      all DPPOS subgroups versus NHANES subgroups of similar age/sex/diabetes status;
      with values as much as twice as high in some DPPOS subgroups. Longitudinal
      questionnaire data from DPP/DPPOS showed a maintained increase of 1.24 MET
      hours/week (p=0.026) of leisure activity in DPPOS participants from all original
      study arms between DPP baseline and accelerometer recording. There were no
      consistent differences between comparable DPPOS and NHANES subgroups for
      accelerometer-derived sedentary or light-intensity activity minutes/day.
      CONCLUSIONS: More than 10 years after the start of DPP, DPPOS participants
      performed more accelerometer-measured MVPA than similar adults from NHANES.
      Longitudinal questionnaire data support the accelerometer-based findings by
      suggesting that leisure activity levels at the time of accelerometer recording
      remained higher than DPP baseline levels.

PMID- 27887771
TI  - Microbiological Research Under the Nagoya Protocol: Facts and Fiction.
AB  - The Nagoya Protocol is based on concepts of biological diversity that are hardly
      applicable to microorganisms. Because of this incongruence, the Nagoya Protocol
      threatens future microbial research, potentially defeating its original purpose.
      Countries with appropriate regulations can promote science and their bioeconomy
      through international collaboration and simultaneously gain a competitive
      advantage.

PMID- 27887772
TI  - Dechlorination of organochloride waste mixture by microwave irradiation before
      forming solid recovered fuel.
AB  - In order to form a modified solid recovered fuel (SRF) with low chlorine content,
      high calorific value and well combustion performance, low temperature microwave
      irradiation was applied to remove the chlorine of the organochloride waste
      mixture before they were mixed to form SRF. The optimizing conditions of final
      temperature, microwave absorbents and heating rate were also detected to obtain
      high dechlorination ratio and high ratio of hydrogen chloride (HCl) to volatiles.
      In the temperature range of 220-300 degrees C, 280 degrees C would be chose as
      the optimal low microwave modified temperature concerning at which the
      dechlorination ratio was high and ratio of HCl to volatiles was relatively high
      as well; The use of microwave absorbents of graphite and silicon carbide (SiC)
      had a pronounced effect on the dechlorination of organochloride waste mixture,
      and the dechlorination ratio was increased significantly which could be reached
      to 87%, almost 20% higher than absorbent absent sample; The heating rate should
      set be not too fast nor too slow, and there was no big difference between the
      heating rate of 13 degrees C/min and 15 degrees C/min; The content of Cl of
      modified SRF is dramatically decreased and reaches to a low level 0.328%. Hence,
      the modified SRF can be ascended from the third class to the second class
      according to the Finland chlorine Classes I-III. Moreover, the combustibility of
      modified SRF was substantial improved compared to the traditional SRF. The low
      heating value was almost 20.56MJ/kg which is close to the LHV of lignite coal and
      bituminous coal in China, and it increased by 60% over that of traditional SRF.
      Removing chlorine of organochloride waste mixture before they are mixed with
      other kinds of combustible waste to form a modified SRF which is expected to be
      an alternative fuel for combustion in the future.

PMID- 27887773
TI  - Estimation of fugitive landfill methane emissions using surface emission
      monitoring and Genetic Algorithms optimization.
AB  - As municipal solid waste (MSW) landfills can generate significant amounts of
      methane, there is considerable interest in quantifying fugitive methane emissions
      at such facilities. A variety of methods exist for the estimation of methane
      emissions from landfills. These methods are either based on analytical emission
      models or on measurements. This paper presents a method to estimate methane
      emissions using ambient air methane measurements obtained on the surface of a
      landfill. Genetic Algorithms based optimization combined with the standard
      Gaussian dispersion model is employed to identify locations as well as emission
      rates of potential emission sources throughout a municipal solid waste landfill.
      Four case studies are employed in order to evaluate the performance of the
      proposed methodology. It is shown that the proposed approach enables estimation
      of landfill methane emissions and localization of major emission hotspots in the
      studied landfills. The proposed source-locating-scheme could be seen as a cost
      effective method assisting landfill operators to reasonably estimate and locate
      major methane emissions.

PMID- 27887775
TI  - Bactericidal dental nanocomposites containing 1,2,3-triazolium-functionalized
      POSS additive prepared through thiol-ene click polymerization.
AB  - OBJECTIVE: Deterioration of mechanical strength for the dental composite
      containing ionic bactericidal compounds restricts the widespread utilization of
      this class of useful materials. This problem is originated from the reduction of
      the intermolecular interaction of polymeric network due to plasticization effect
      of absorbed water molecules penetrated between the chain segments. The main goal
      of this study is the synthesis of the highly efficient bactericidal additive with
      low hydrophilicity and consequently the least adverse effect on the final
      mechanical strength of the dental composite. METHODS: The bactericidal 1, 2, 3
      triazolium functional groups were chemically anchored on the surface of
      hydrophobic POSS nanoparticles (Triazolium-POSS) and incorporated into a dental
      restorative system composed of a ternary thiol-allyl ether-methacrylate resin and
      glass fillers. A similar system was also prepared, in which the POSS additive was
      replaced with quaternized dimethyl aminoethyl methacrylate monomer (DMAEMA-BC).
      The chemical structure of POSS derivatives was evaluated by 1HNMR and FTIR
      spectra. The water uptake of dental composites was evaluated at days 1 and 14
      after immersion into water. The bactericidal activity of composite specimens
      against Streptococcus mutans (ATCC 35668) was determined based on ASTM E 2180 -
      07. The flexural properties of samples were investigated through three-point
      bending assay and the shrinkage-strain of photo-cured resins was measured using
      the bonded-disk technique. The degree of conversion (DC %) of methacrylate
      functions was followed by FTIR spectroscopy. MTT assay was performed to
      investigate the cytocompatibility of samples. RESULTS: Regardless of the partial
      increase in water uptake for Triazolium-POSS-containing sample, this parameter
      was much favor than the composite made from DMAEMA-BC. Therefore, the lower
      decline in flexural properties was recorded under the wet condition for the
      former system. Incorporation of Triazolium-POSS had no significant effect on
      shrinkage strain and cytocompatibility of composite specimen, meanwhile, a higher
      degree of conversion of methacrylate functional groups was recorded. The
      Triazolium-POSS-containing nano composite showed significantly higher
      bactericidal activity against Streptococcus mutans than another studied model
      system. SIGNIFICANCE: The new derivative of bactericidal POSS nanoparticles
      decorated with 1, 2, 3-Triazolium moieties is a highly efficient bactericidal
      compound. If Triazolium-POSS is incorporated into a proper dental resin
      formulation, it can provide a strong bactericidal activity for dental materials;
      in the meantime, it leads to minimum deterioration of their mechanical strength
      due to its low water uptake.

PMID- 27887774
TI  - Rationale and study design of RESPITE: An open-label, phase 3b study of riociguat
      in patients with pulmonary arterial hypertension who demonstrate an insufficient
      response to treatment with phosphodiesterase-5 inhibitors.
AB  - Patients with pulmonary arterial hypertension (PAH) who do not have an adequate
      response to therapy with phosphodiesterase-5 inhibitors (PDE-5i) may have
      insufficient synthesis of cyclic guanosine monophosphate (cGMP). These patients
      may respond to a direct soluble guanylate cyclase (sGC) stimulator such as
      riociguat. RESPITE (NCT02007629) was an open-label, multicenter, uncontrolled,
      single-arm phase 3b study of riociguat in patients with PAH who demonstrated an
      insufficient response to treatment with PDE-5i. Insufficient response was defined
      as World Health Organization functional class (WHO FC) III despite PDE-5i therapy
      for at least 90 days; 6-min walk distance (6MWD) of 165-440 m, and right-heart
      catheterization showing mean pulmonary artery pressure >30 mmHg, cardiac index
      <3.0 L/min/m2, and pulmonary vascular resistance >400 dyn s cm-5. PAH patients
      with an insufficient response to stable doses of sildenafil or tadalafil-either
      as monotherapy or in combination with an endothelin receptor antagonist-for at
      least 90 days were switched to riociguat for 24 weeks. Starting at 1.0 mg TID,
      the dose of riociguat was increased during the 8-week titration phase in 0.5-mg
      increments in 2-week intervals if the patient had no signs or symptoms of
      hypotension. In the ensuing 16-week maintenance phase, riociguat was continued at
      the optimal individual dose. All efficacy outcomes were exploratory and include
      change from baseline to 24 weeks in 6MWD, cardiac index, N-terminal pro-brain
      natriuretic peptide, WHO FC, and quality of life and the proportion of patients
      with clinical worsening. The following biomarkers were to be measured: cGMP,
      asymmetric dimethyl arginine, growth-differentiation factor-15, and ST2. Results
      from RESPITE will help to determine if PAH patients who do not respond to PDE-5i
      are likely to benefit from treatment with an sGC stimulator. The study may also
      identify biomarkers that are able to suggest which patients are more likely to
      respond to sGC stimulators.

PMID- 27887776
TI  - Critical role of superoxide anions and hydroxyl radicals in HEMA-induced
      apoptosis.
AB  - OBJECTIVE: Resin monomers such as 2-hydroxyethyl methacrylate (HEMA) induce
      apoptosis because of the excess formation of reactive oxygen species (ROS). The
      portion of ROS including superoxide anions, hydrogen peroxide or hydroxyl
      radicals in monomer-induced apoptosis is unknown. Here, the effectiveness of
      superoxide anions or hydroxyl radicals was analyzed using tempol or sodium
      formate as radical scavengers. METHODS: RAW264.7 mouse macrophages were exposed
      to HEMA (0-6-8mM) in the presence of tempol (0-0.05-0.5-5.0mM) or sodium formate
      (0-1-5-10mM). The formation of ROS using DCFH2-DA or dihydrorhodamine 123
      (DHR123) as fluorescent dyes and the induction of apoptosis was determined by
      flow cytometry after 1h or 24h exposure periods. Expression of enzymes related to
      ROS metabolism was detected by Western blotting. RESULTS: DCF fluorescence
      significantly increased after short exposure (1h) while DHR123 fluorescence was
      enhanced after a long exposure period (24h) in cells treated with HEMA. Although
      no influence was detected on the formation of ROS, tempol or sodium formate
      protected cells from HEMA-induced apoptosis. The number of cells in late
      apoptosis or necrosis induced with 6 or 8mM HEMA was reduced in the presence of
      tempol or low concentrations of sodium formate. HEMA-induced expression of
      catalase, indicating oxidative stress, decreased in the presence of tempol.
      SIGNIFICANCE: Superoxide anions and hydroxyl radicals contribute to HEMA-induced
      apoptosis. The current findings support the development of strategies based on
      the pharmacological inhibition of enzymes producing superoxide anions finally
      converted to hydroxyl radicals to compensate for potential adverse tissue
      reactions associated with dental composites.

PMID- 27887777
TI  - ADAMTS13-specific circulating immune complexes as potential predictors of relapse
      in patients with acquired thrombotic thrombocytopenic purpura.
AB  - BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare
      thrombotic microangiopathy due to the development of autoantibodies against the
      VWF-cleaving protease ADAMTS13. ADAMTS13-specific circulating immune complexes
      (CICs) have been described in patients with acquired TTP, but their clinical
      relevance remained to be established. The aim of this study was to assess the
      association between ADAMTS13-specific CICs and ADAMTS13-related measurements,
      clinical and laboratory markers of disease severity, and occurrence of TTP
      relapse, in autoimmune TTP patients. MATERIAL AND METHODS: We measured ADAMTS13
      specific CICs in 51 patients with severe ADAMTS13 deficiency and anti-ADAMTS13
      autoantibodies, at the first episode of acquired TTP. The associations between
      ADAMTS13-specific CICs and the variables of interest were assessed by linear,
      logistic and Cox proportional hazard regression models, where appropriate.
      RESULTS: The prevalence of ADAMTS13-specific CICs in patients experiencing the
      first TTP episode was 39% (95% confidence intervals [CI]: 26-52%). ADAMTS13
      specific CICs were not associated neither with laboratory markers of disease
      severity, nor with patterns of clinical presentation. Conversely, among 45
      survivors, a positive association was found between the presence of ADAMTS13
      specific CICs and the risk of recurrence within 2years after the first TTP
      episode (adjusted hazard ratio, 3.4 [95% CI: 0.9 to 13.5]). CONCLUSIONS: ADAMTS13
      specific CICs seem to be able to predict the recurrence of acute TTP episodes in
      the first 2years after disease onset. Therefore, their measurement might be used
      as a tool to stratify the risk of disease relapse, with potential influence on
      surveillance and therapeutic choices during remission phase.

PMID- 27887779
TI  - Challenges facing the identification of distinctive cognitive and neurobiological
      features of schizophrenia and bipolar disorder and the need for a data-driven
      approach: Response to Dr. Martino.

PMID- 27887778
TI  - Cultivation of four microalgae species in the effluent of anaerobic digester for
      biodiesel production.
AB  - This study investigated if an effluent from anaerobic digestion (AD) system can
      be used as a nutrients source for the microalgae cultivation, and in so doing, if
      the effluent can be properly treated. Nitrogen and phosphorus in the AD effluent
      well supported microalgal growth, and their removal efficiency reached >97.9% and
      99.2%, respectively. Among four different algal species tested, Micractinium
      inermum particularly stood out, showing the highest biomass and FAME
      productivity: 0.16gL-1d-1 with 3.23gL-1 of dry cell weight, and 0.04gL-1d-1 with
      27.54% (w/w) of FAME contents, respectively. As the concentrations of the
      nutrients decreased over time, the FAME contents were increased and its quality
      as well, satisfying several biodiesel quality standards. This study supports that
      the AD effluent can indeed serve as a cheap and nutrient-rich medium for
      microalgae cultivation, and equally importantly, microalgae can be a workable
      treatment option for it.

PMID- 27887780
TI  - Insight and white matter fractional anisotropy in first-episode schizophrenia.
AB  - Impaired insight is a hallmark feature of schizophrenia. Structural studies
      implicate predominantly prefrontal, cingulate, cuneus/precuneus, and inferior
      temporal brain regions. The cortical midline structures (CMS) are also implicated
      in functional studies primarily through self-reflective processing tasks.
      However, few studies have explored the relationship between white matter tracts
      and insight in schizophrenia, and none in first-episode schizophrenia (FES).
      Here, we examined for fractional anisotropy (FA) differences in 89 minimally
      treated FES patients and 98 matched controls, and identified those FA differences
      associated with impaired clinical insight in patients. We found widespread FA
      reduction in FES patients compared to controls. Poorer insight in patients was
      predicted by lower FA values in a number of white matter tracts with a
      predilection for tracts associated with cortical midline structures (fronto
      occipital, cingulate, cingulate hippocampus, uncinate, anterior corona radiata),
      and more severe depressive symptoms. The association between FA abnormalities and
      insight was most robust for the awareness of symptoms and illness awareness
      domains. Our study implicates a network of tracts involved in impaired insight in
      schizophrenia with a predilection for the CMS. This study is a first step in
      delineating the white matter tracts involved in insight impairment in
      schizophrenia prior to chronicity.

PMID- 27887781
TI  - High psychosis liability is associated with altered autonomic balance during
      exposure to Virtual Reality social stressors.
AB  - BACKGROUND: Social stressors are associated with an increased risk of psychosis.
      Stress sensitisation is thought to be an underlying mechanism and may be
      reflected in an altered autonomic stress response. Using an experimental Virtual
      Reality design, the autonomic stress response to social stressors was examined in
      participants with different liability to psychosis. METHOD: 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 were exposed to
      social stressors (crowdedness, ethnic minority status and hostility) in a Virtual
      Reality environment. Heart rate variability parameters and skin conductance
      levels were measured at baseline and during Virtual Reality experiments. RESULTS:
      High psychosis liability groups had significantly increased heart rate and
      decreased heart rate variability compared to low liability groups both at
      baseline and during Virtual Reality experiments. Both low frequency (LF) and high
      frequency (HF) power were reduced, while the LF/HF ratio was similar between
      groups. The number of virtual social stressors significantly affected heart rate,
      HF, LF/HF and skin conductance level. There was no interaction between psychosis
      liability and amount of virtual social stress. CONCLUSION: High liability to
      psychosis is associated with decreased parasympathetic activity in virtual social
      environments, which reflects generally high levels of arousal, rather than
      increased autonomic reactivity to social stressors.

PMID- 27887782
TI  - Ambient particulate matter, landscape fire smoke, and emergency ambulance
      dispatches in Sydney, Australia.
AB  - BACKGROUND: Emergency ambulance dispatches (EAD) are a novel outcome for
      evaluating the public health impacts of air pollution. We assessed the
      relationships between ambient particulate matter (PM) from all sources, PM from
      landscape fire smoke (LFS), and EADs likely to be associated with
      cardiorespiratory problems in the Sydney greater metropolitan region for an 11
      year period from 2004 to 2015. METHODS: EAD codes are assigned at the time of the
      call to emergency services using standard computer assisted algorithms. We
      assessed EADs coded as: breathing problems, chest pain, stroke or cerebrovascular
      accident (stroke), cardiac or respiratory arrest and death (arrest), and heart or
      defibrillator problems (other heart problems). Using a daily times series study
      design with a generalized linear Poisson regression model we quantified the
      association between EAD and daily PM2.5 from all sources (PM2.5,all) and PM2.5
      primarily due to LFS (PM2.5,LFS). RESULTS: Increases of 10MUg.m-3 in PM2.5,all
      were positively associated with same day EAD for breathing problems (RR=1.03, 95%
      CI 1.02 to 1.04), arrest (RR=1.03, 95% CI 1.00 to 1.06), and chest pain (RR=1.01
      CI 1.00 to 1.02) but not with other outcomes. Increases of 10MUg.m-3 PM2.5,LFS
      were also positively associated with breathing problems on the same day (RR=1.04,
      95% CI 1.02 to 1.05) and other heart problems at lag of two days (RR=1.05, 95% CI
      1.01 to 1.09). CONCLUSIONS: Emergency dispatches for breathing problems are
      associated with PM2.5,all and PM2.5,LFS and provide a sensitive end point for
      continued research and surveillance activities investigating the impacts of daily
      fluctuations in ambient PM2.5.

PMID- 27887783
TI  - A systematic review of Mancozeb as a reproductive and developmental hazard.
AB  - BACKGROUND: The potential adverse reproductive and developmental effects of
      Mancozeb, especially in sensitive subpopulations, have not been fully reviewed
      for this widely used fungicide. OBJECTIVE: To review the experimental and
      epidemiologic evidence for the association between exposure to Mancozeb and
      reproductive and developmental health outcomes using an adaptation of the
      National Toxicology Program's Office of Health Assessment and Translation (OHAT)
      systematic review framework. DATA SOURCES: Four databases (PubMed, TOXNET, Web of
      Science, Google Scholar) were searched for published studies on Mancozeb. Of 403
      identified articles, 30 met our inclusion criteria for systematic review.
      RESULTS: Results from in vitro studies provide evidence that Mancozeb may
      indirectly disrupt or impair reproduction at the cellular level and should be
      regarded as a reproductive toxicant. Animal studies confirm reproductive and
      developmental toxicity in mammals and suggest that males chronically exposed to
      Mancozeb experience significant changes in physiological, biochemical, and
      pathological processes that may lead to infertility. Epidemiological studies were
      limited to indirect methods of exposure assessment and examined the effect of
      fungicides more broadly during pre-conception, pregnancy, and birth, yielding
      mixed results. CONCLUSIONS: High confidence ratings from in vitro and animal
      studies, in combination with moderate confidence ratings from epidemiologic
      studies employing indirect methods of exposure assessment, provide evidence that
      Mancozeb should be regarded as a suspected developmental hazard and a presumed
      reproductive hazard in humans. More population-based studies linking direct
      measures and/or biomarkers of exposure to adverse effects on male and female
      fertility, as well as in utero and early life development, are needed to improve
      the quality of the evidence base concerning the human reproductive and
      developmental consequences of Mancozeb exposure.

PMID- 27887784
TI  - Endoscopic debridement and fibrin glue injection of a chronic Morel-Lavallee
      lesion of the knee in a professional soccer player: A case report and literature
      review.
AB  - A Morel-Lavallee lesion is a post-traumatic closed degloving injury of soft
      tissue. The lesion is due to a shearing trauma with separation of subcutaneous
      tissue from underlying fascia. When conservative treatment fails, surgical
      treatment is imperative. Commonly, open drainage and debridement is performed.
      This case report describes a Morel-Lavallee lesion of the knee in a professional
      soccer player who was successfully treated with endoscopic debridement and fibrin
      glue injection after failure of conservative management. This method achieves the
      goal of an open surgical debridement without exposing patients to an increased
      morbidity.

PMID- 27887785
TI  - Thromboelastography (TEG(r)) demonstrates that tinzaparin 4500 international
      units has no detectable anticoagulant activity after caesarean section.
AB  - BACKGROUND: Low molecular weight heparin is routinely used for thromboprophylaxis
      in pregnancy and the puerperium. Consensus guidelines recommend waiting 10-12h
      after administration of a thromboprophylactic dose of low molecular weight
      heparin before performing a neuraxial block or removing an epidural catheter.
      Thromboelastography (TEG(r)) has been reported to be sensitive to the effects of
      enoxaparin 4h after administration. The purpose of this study was to use TEG to
      examine coagulation changes in the first 10h after a thromboprophylactic dose of
      tinzaparin in an attempt to ratify the current consensus guidelines about timing
      of neuraxial blockade and epidural catheter removal. METHODS: Twenty-four women
      who had undergone caesarean delivery and were classified as low or intermediate
      risk of thrombosis were recruited. Blood samples were taken before subcutaneous
      administration of tinzaparin 4500IU, and at 4, 8 and 10h post-dose. Standard TEG
      analyses were performed using plain and heparinase cuvettes and samples were also
      sent for laboratory anti-Xa assay. Thromboelastograph profiles were analysed for
      a low molecular weight heparin effect. RESULTS: Analysis revealed no significant
      differences in R time, K time, alpha angle or maximum amplitude between plain and
      heparinase samples at any time point. Apart from a small statistically
      significant (P=0.033) decrease in maximum amplitude of 2.8% (95% CI 0.3 to 5.4%)
      at 4h, there were no significant changes in coagulation for any TEG parameter.
      Anti-Xa levels were virtually undetectable in all patients over the 10h period
      (median 0.00U/mL; range 0.00-0.13U/mL). CONCLUSION: A thromboprophylactic dose of
      tinzaparin 4500IU had little detectable effect on coagulation as assessed by TEG
      and anti-Xa assay. These findings support consensus guidelines which state that
      it is acceptable to perform neuraxial blockade or remove an epidural catheter 10
      12h after a thromboprophylactic dose of tinzaparin. Rather than suggesting a lack
      of anticoagulant activity, the findings indicate that TEG may not have the
      sensitivity to detect a tinzaparin effect when this dose is used in this patient
      group.

PMID- 27887786
TI  - Validity and reliability of Fitbit activity monitors compared to ActiGraph GT3X+
      with female adults in a free-living environment.
AB  - OBJECTIVES: Inexpensive activity monitors have recently gained popularity with
      the general public. Researchers have evaluated these consumer-based monitors in
      laboratory-conditions. Given the current wide-spread consumer use of these
      devices, it is important to ensure users are attaining accurate information
      compared to previously validated measures. This study investigates the accuracy
      of Fitbit One and Flex activity monitors in measuring steps, sedentary time, and
      time spent in light, moderate, and vigorous intensity activities with ActiGraph
      GT3X+ with female adults in free-living conditions. DESIGN: Cross-sectional
      study. METHODS: Twenty-two women, 21.23+/-1.63 years, BMI: 22.35+/-2.34kg/m2 wore
      two Fitbit Ones (bra and waist), one Fitbit Flex on the wrist, and one ActiGraph
      GT3X+ on the waist for seven-consecutive days. Repeated measures ANOVA was used
      to explore differences in steps, sedentary time, and time spent in light,
      moderate and vigorous intensity activities among the four devices. RESULTS: No
      differences were found in number of steps recorded across the four devices.
      Fitbit One, waist and bra, overestimated time spent in light intensity
      activities. Fitbit One (waist) and Fitbit Flex overestimated time spent in
      moderate intensity activities. Fitbit One, waist and bra, and Fitbit Flex
      overestimated time spent in vigorous intensity activities. All Fitbit activity
      monitors overestimated MVPA and underestimated sedentary time compared to the
      ActiGraph. CONCLUSIONS: Regardless of wear-location all Fitbit devices provide
      similar activity monitoring and users can wear the devices wherever best
      accommodates their lifestyle or needs. Users should not rely solely on these
      monitors when tracking vigorous and MVPA activities.

PMID- 27887787
TI  - Vascular endothelial growth factor (VEGF) and platelet-derived growth factor
      (PDGF) levels in the cerebrospinal fluid of children with influenza-associated
      encephalopathy.
AB  - INTRODUCTION: To search for an index of neurologic prognosis of children with
      influenza-associated encephalopathy (IAE), involvement of angiogenesis-related
      growth factors in the pathology was investigated. PATIENTS AND METHODS: The
      subjects were 11 IAE patients, 6 patients with bacterial meningitis (BM), and 24
      patients with non-central nervous system infection as a control group admitted to
      our hospital. The correlation between the vascular endothelial growth factor
      (VEGF) and platelet-derived growth factor (PDGF) levels in cerebrospinal fluid
      and the relationship with an index of inflammatory marker, interleukin (IL)-6,
      were investigated. Using the Pediatric Cerebral Performance Categories (PCPC)
      score as a prognostic indicator, we evaluated the association between the
      biomarkers and neurologic prognosis. RESULT: PDGF significantly increased in the
      IAE group compared with that in the BM group. Cerebrospinal fluid VEGF and PDGF
      increased in all IAE and BM patients compared with that in the control group, and
      VEGF and PDGF were positively correlated in the 2 groups. No correlation was
      found between the cerebrospinal fluid VEGF and PDGF levels and IL-6 level in the
      IAE group, whereas a correlation was found in the BM group. All these factors
      increased in patients with poor neurologic prognosis. DISCUSSION: It is possible
      that the disease state of IAE can be evaluated based on vascular endothelial
      disorder-related markers.

PMID- 27887788
TI  - Hospital admission volume does not impact the in-hospital mortality of acute
      pancreatitis.
AB  - BACKGROUND: Multiple factors influence mortality in Acute Pancreatitis (AP).
      METHODS: To evaluate the association of demographic, clinical, and hospital
      factors with the in-hospital mortality of AP using a population-based
      administrative database. The Maryland HSCRC database was queried for adult (>=18
      years) admissions with primary diagnosis of AP between 1/94-12/10. Organ failure
      (OF), interventions, hospital characteristics and referral status were evaluated.
      RESULTS: There were 72,601 AP admissions across 48 hospitals in Maryland with 885
      (1.2%) deaths. A total of 1657 (2.3%) were transfer patients, of whom 101 (6.1%)
      died. Multisystem OF was present in 1078 (1.5%), of whom 306 (28.4%) died. On
      univariable analysis, age, male gender, transfer status, comorbidity, OF, all
      interventions, and all hospital characteristics were significantly associated
      with mortality; however, only age, transfer status, OF, interventions, and large
      hospital size were significant in the adjusted analysis. Patients with commercial
      health insurance had significantly less mortality than those with other forms of
      insurance (OR 0.65, 95% CI: 0.52, 0.82, p = 0.0002). CONCLUSION: OF is the
      strongest predictor of mortality in AP after adjusting for demographic, clinical,
      and hospital characteristics. Admission to HV or teaching hospital has no
      survival benefit in AP after adjusting for OF and transfer status.

PMID- 27887789
TI  - Relationship between caries, body mass index and social class in Spanish
      children.
AB  - OBJECTIVE: To determine the association between caries, body mass index (BMI) and
      social class in child population of the Valencia region (Spain) at 6, 12 and 15
      years, and study. METHODS: In a cross sectional study of 1326 children aged 6
      (n=488), 12 (n=409) and 15 years (n=433) who took part in the 2010 Oral Health
      Survey of the Valencia region, the ICDAS II criteria were employed for diagnosing
      and coding all the teeth examined. The quantitative BMI values on a continuous
      scale were grouped into 3 categories (normal weight, overweight, obese) based on
      a table adjusted for age and gender. The highest-ranking occupation of the
      parents was taken to indicate the social class of the child. RESULTS: The mean
      BMI was 17.21 at 6 years, 21.39 at 12 years and 22.38 at 15 years. No significant
      differences in caries indexes (DMFT or dft) by degree of obesity stratified by
      social class were found in any of the age groups studied. There was no
      significant correlation between BMI and DMFT-dft in any of the age groups.
      CONCLUSIONS: Obesity is not associated with dental caries in schoolchildren of
      this population.

PMID- 27887790
TI  - In Response.

PMID- 27887791
TI  - Cryptogenic Stroke and Nonstenosing Intracranial Calcified Atherosclerosis.
AB  - OBJECTIVE: Because some cryptogenic strokes may result from large-artery
      atherosclerosis that goes unrecognized as it causes <50% luminal stenosis, we
      compared the prevalence of nonstenosing intracranial atherosclerotic plaques
      ipsilateral to cryptogenic cerebral infarcts versus the unaffected side using
      imaging biomarkers of calcium burden. METHODS: In a prospective stroke registry,
      we identified patients with cerebral infarction limited to the territory of one
      internal carotid artery (ICA). We included patients with stroke of undetermined
      etiology and, as controls, patients with cardioembolic stroke. We used
      noncontrast computed tomography to measure calcification in both intracranial
      ICAs, including qualitative calcium scoring and quantitative scoring utilizing
      the Agatston-Janowitz (AJ) calcium scoring. Within subjects, the Wilcoxon signed
      rank sum test for nonparametric paired data was used to compare the calcium
      burden in the ICA upstream of the infarction versus the ICA on the unaffected
      side. RESULTS: We obtained 440 calcium measures from 110 ICAs in 55 patients.
      Among 34 patients with stroke of undetermined etiology, we found greater calcium
      in the ICA ipsilateral to the infarction (mean Modified Woodcock Visual Scale
      score, 6.7 +/- 4.6) compared with the contralateral side (5.4 +/- 4.1) (P =
      .005). Among 21 patients with cardioembolic stroke, we found no difference in
      calcium burden ipsilateral to the infarction (6.7 +/- 5.9) versus the
      contralateral side (7.3 +/- 6.3) (P = .13). The results were similar using
      quantitative calcium measurements, including the AJ calcium scores. CONCLUSION:
      In patients with strokes of undetermined etiology, the burden of calcified
      intracranial large-artery plaque was associated with downstream cerebral
      infarction.

PMID- 27887792
TI  - Edaravone with and without .6 Mg/Kg Alteplase within 4.5 Hours after Ischemic
      Stroke: A Prospective Cohort Study (PROTECT4.5).
AB  - BACKGROUND: Edaravone is widely used to treat acute ischemic stroke (AIS) within
      24 hours of onset. We aimed to evaluate current edaravone treatment practices and
      the efficacy and safety of edaravone used with recombinant tissue plasminogen
      activator (tPA) in AIS patients within 4.5 hours of onset. The results were
      compared with those of the Safe Implementation of Treatments in Stroke
      International Stroke Thrombolysis Registry (SITS-ISTR) study. METHODS: PROTECT4.5
      was a prospective observational study conducted from April 2010 to March 2013 in
      Japan. The primary end points were favorable outcomes (modified Rankin Scale
      score [mRS] 0-1) at 3 months after onset and incidence of symptomatic
      intracranial hemorrhage (sICH) within 36 hours of treatment. For comparison with
      SITS-ISTR, patients were categorized based on the time from onset to treatment
      (within 3 hours of and 3-4.5 hours after onset) and baseline National Institutes
      of Health Stroke Scale score (NIHSS). RESULTS: Among the 11,384 registered
      patients, 11,126 and 8274 patients were included in the safety and efficacy
      analysis populations, respectively. The proportions of patients with mRS 0-1
      receiving edaravone alone and edaravone + tPA were 51.3% (95% confidence
      interval, 49.7%-52.8%) and 39.0% (37.6%-40.5%), respectively. The incidence of
      sICH within 36 hours after tPA treatment (edaravone + tPA group) was 1.6% (1.3%
      2.0%). When compared with the SITS-ISTR results, those treated with edaravone +
      tPA appeared to show better outcomes in patients with NIHSS score >=16.
      CONCLUSIONS: The efficacy and safety of edaravone combined with tPA and
      administered within 4.5 hours of AIS onset were demonstrated with numerically
      lower incidence of sICH and better outcomes.

PMID- 27887793
TI  - Antiproliferative and antimetastatic action of quercetin on A549 non-small cell
      lung cancer cells through its effect on the cytoskeleton.
AB  - To our knowledge, this study is the first to investigate the effect of the
      dietary flavonoid quercetin on the main cytoskeletal elements, namely
      microfilaments, microtubules and vimentin intermediate filaments, as well as
      cytoskeleton-driven processes in A549 non-small cell lung cancer cells. The
      methyl-thiazol-diphenyl-tetrazolium assay, annexin V/propidium iodide test,
      electron microscopic examination, cell cycle analysis based on DNA content, real
      time PCR assays, in vitro scratch wound-healing assay, fluorescence staining of F
      actin, beta-tubulin and vimentin were performed to assess the effects of
      quercetin on A549 cells. Our results showed that quercetin triggered BCL2/BAX
      mediated apoptosis, as well as necrosis and mitotic catastrophe, and inhibited
      the migratory potential of A549 cells. The disassembling effect of quercetin on
      microfilaments, microtubules and vimentin filaments along with its inhibitory
      impact on vimentin and N-cadherin expression might account for the decreased
      migration of A549 cells in response to quercetin treatment. We also suggest that
      the possible mechanism underlying quercetin-induced mitotic catastrophe involves
      the perturbation of mitotic microtubules leading to monopolar spindle formation,
      and, consequently, to the failure of cytokinesis. We further propose that
      cytokinesis failure could also be a result of the depletion of actin filaments by
      quercetin. These findings are important to our further understanding of the
      detailed mechanism of the antitumor activity of quercetin and render this
      flavonoid a potentially useful candidate for combination therapy with
      conventional antimicrotubule drugs, nucleic acid-directed agents or novel
      cytoskeletal-directed agents.

PMID- 27887794
TI  - Retinoschisis and neurosensory detachment in advanced focal glaucoma.
AB  - CLINICAL CASE: A 71-year-old woman with normotensive primary open-angle glaucoma
      presented with an asymptomatic temporal peripapillary retinoschisis, associated
      with serous retinal detachment in the eye with the more advanced glaucoma. It was
      located at the inferior pole of the optic disc, in the proximity of a
      glaucomatous focal disc defect. DISCUSSION: Although congenital optic pits are
      strongly related with juxta-papillary retinoschisis, retinoschisis can also arise
      from acquired defects in the proximity of glaucomatous optic discs. As symptoms
      depend on the extent of the retinoschisis, the prevalence of this complication
      could be greater than that reported in glaucomatous eyes.

PMID- 27887795
TI  - Clinician knowledge, clinician barriers, and perceived parental barriers
      regarding human papillomavirus vaccination: Association with initiation and
      completion rates.
AB  - PURPOSE: We tested the hypothesis that clinician knowledge, clinician barriers,
      and perceived parental barriers relevant to the human papillomavirus (HPV)
      vaccination account for the variation in vaccine delivery at the practice-site
      level. METHODS: We conducted a survey from October 2015 through January 2016
      among primary care clinicians (n=280) in a 27-county geographic region to assess
      clinician knowledge, clinician barriers, and perceived parental barriers
      regarding HPV vaccination. Primary care clinicians included family medicine
      physicians, general pediatricians, and family and pediatric nurse-practitioners.
      We also used the Rochester Epidemiology Project to measure HPV vaccination
      delivery. Specifically we used administrative data to measure receipt of at least
      one valid HPV vaccine dose (initiation) and receipt of three valid HPV vaccine
      doses (completion) among 9-18year old patients residing in the same 27-county
      geographic region. We assessed associations of clinician survey data with
      variation in vaccine delivery at the clinical site using administrative data on
      patients aged 9-18years (n=68,272). RESULTS: Consistent with our hypothesis, we
      found that greater knowledge of HPV and the HPV vaccination was associated with
      higher rates of HPV vaccination initiation (Incidence rate ratio [IRR]=1.05) and
      completion of three doses (IRR=1.28). We also found support for the hypothesis
      that greater perceived parental barriers to the HPV vaccination were associated
      with lower rates of initiation (IRR=0.94) and completion (IRR=0.90). These IRRs
      were statistically significant even after adjustment for site-level
      characteristics including percent white, percent female, percent ages 9-13, and
      percent with government insurance or self-pay at each site. CONCLUSIONS:
      Clinician knowledge and their report of the frequency of experiencing parental
      barriers are associated with HPV vaccine delivery rates-initiation and
      completion. Higher measures of knowledge correlated with higher rates. Fewer
      perceived occurrences of parental barriers correlated with lower rates. These
      data can guide efforts to improve HPV vaccine delivery in clinical settings.

PMID- 27887797
TI  - Mortality burden and prognosis of thin melanomas overall and by subcategory of
      thickness, SEER registry data, 1992-2013.
AB  - BACKGROUND: Thin melanomas cause a high death toll despite excellent prognosis.
      OBJECTIVE: We examined melanoma mortality burden and prognosis by categories of
      thickness within Surveillance, Epidemiology, and End Results (SEER) 13 Registry
      1992-2013. METHODS: We divided 49,319 stage I and II melanoma cases diagnosed
      between 1992 and 2003 into T1 through T4 and then subdivided T1 into 0.01-0.25
      mm, 0.26-0.50 mm, 0.51-0.75 mm, and 0.76-1.00 mm categories. We determined the
      number and proportion of deaths due to melanoma within 10 years of diagnosis for
      each thickness category and proportions within T1 subcategories with ulceration.
      RESULTS: We confirmed prognosis worsened as melanoma thickened from T1 to T4;
      however, most deaths resulted from melanomas that were diagnosed at the T1 stage.
      The smallest number of deaths within T1 resulted from 0.01-0.25 mm-thick
      melanomas; however, the risk for death within 10 years was greater for those
      diagnosed with melanoma when tumor depth was 0.01-0.25 mm than for those
      diagnosed when tumor depth was 0.26-0.50 mm. Prognosis worsened with depths
      starting at 0.51 mm. The pattern within T1 was not explained by ulceration.
      LIMITATIONS: We did not evaluate melanoma subtype, mitotic rate, or other
      associated features. CONCLUSION: Thin melanomas are a substantial public health
      burden. Efforts should be made to diagnose melanoma at the in situ stage.

PMID- 27887796
TI  - Vaccine strategies: Optimising outcomes.
AB  - Successful immunisation programmes generally result from high vaccine
      effectiveness and adequate uptake of vaccines. In the development of new
      vaccination strategies, the structure and strength of the local healthcare system
      is a key consideration. In high income countries, existing infrastructures are
      usually used, while in less developed countries, the capacity for introducing new
      vaccines may need to be strengthened, particularly for vaccines administered
      beyond early childhood, such as the measles or human papillomavirus (HPV)
      vaccine. Reliable immunisation service funding is another important factor and
      low income countries often need external supplementary sources of finance. Many
      regions also obtain support in generating an evidence base for vaccination via
      initiatives created by organisations including World Health Organization (WHO),
      the Pan American Health Organization (PAHO), the Agence de Medecine Preventive
      and the Sabin Vaccine Institute. Strong monitoring and surveillance mechanisms
      are also required. An example is the efficient and low-cost approaches for
      measuring the impact of the hepatitis B control initiative and evaluating
      achievement of goals that have been established in the WHO Western Pacific
      region. A review of implementation strategies reveals differing degrees of
      success. For example, in the Americas, PAHO advanced a measles-mumps-rubella
      vaccine strategy, targeting different population groups in mass, catch-up and
      follow-up vaccination campaigns. This has had much success but coverage data from
      some parts of the region suggest that children are still not receiving all
      appropriate vaccines, highlighting problems with local service infrastructures.
      Stark differences in coverage levels are also observed among high income
      countries, as is the case with HPV vaccine implementation in the USA versus the
      UK and Australia, reflecting differences in delivery settings. Experience and
      research have shown which vaccine strategies work well and the factors that
      encourage success, which often include strong support from government and
      healthcare organisations, as well as tailored, culturally-appropriate local
      approaches to optimise outcomes.

PMID- 27887798
TI  - Development and validation of a patient-reported outcome measure in vitiligo: The
      Self Assessment Vitiligo Extent Score (SA-VES).
AB  - BACKGROUND: The Vitiligo Extent Score (VES) has recently been introduced as a
      physicians' score for the clinical assessment of the extent of vitiligo, but a
      good patient self-assessment score is lacking. OBJECTIVE: The objective is to
      develop and validate a simplified version of the VES as a patient-reported
      outcome measure (PROM). METHODS: After extensive pilot testing, patients were
      asked to score their vitiligo extent twice with an interval of 2 weeks using the
      Self Assessment Vitiligo Extent Score (SA-VES). The scores were compared with the
      physicians' evaluation (VES). RESULTS: The SA-VES demonstrated very good test
      retest reliability (intraclass correlation = 0.948, 95% confidence interval [CI]:
      0.911-0.970) that was not affected by age, skin type, or vitiligo distribution
      pattern. According to patients, this evaluation method was easy to use (22% very
      easy; 49% easy; 29% normal) and required <5 minutes in the majority of patients
      (73%, <5 minutes; 24%, 5-10 minutes; 2%, 10-15 minutes). Comparison of the SA-VES
      and the VES demonstrated excellent correlation (r = 0.986, P <.001). LIMITATIONS:
      Few patients had a dark skin type. CONCLUSION: The results demonstrate excellent
      reliability of the SA-VES and excellent correlation with its investigator
      reported counterpart (VES). This patient-oriented evaluation method provides a
      useful tool for the assessment of vitiligo extent.

PMID- 27887799
TI  - Procedural and longer-term outcomes of wire- versus device-based antegrade
      dissection and re-entry techniques for the percutaneous revascularization of
      coronary chronic total occlusions.
AB  - BACKGROUND: There are few data regarding the procedural and follow-up outcomes of
      different antegrade dissection/re-entry (ADR) techniques for chronic total
      occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We compiled a
      multicenter registry of consecutive patients undergoing ADR-based CTO PCI at four
      high-volume specialized institutions. Patients were divided according to the
      specific ADR technique used: subintimal tracking and re-entry (STAR), limited
      antegrade subintimal tracking (LAST), or device-based with the CrossBoss/Stingray
      system (Boston Scientific, Marlborough, MA). Major adverse cardiac events (MACE:
      cardiac death, target-vessel myocardial infarction and target-vessel
      revascularization) on follow-up were the main outcome of this study. Independent
      predictors of MACE were sought with Cox regression analysis. RESULTS: A total of
      223 patients were included (STAR n=39, LAST n=68, CrossBoss/Stingray n=116).
      Baseline characteristics were similar across groups. Technical and procedural
      success was lower with STAR (59% and 59%), as compared with LAST (96% and 96%)
      and CrossBoss/Stingray (89% and 87%; p<0.001 for both). At 24-month follow-up,
      MACE rates were higher in STAR (15.4%) and LAST (17.5%), as compared with device
      based ADR with CrossBoss/Stingray (4.3%, p=0.02), driven by TVR (7.7% vs. 15.5%
      vs. 3.1%, respectively; p=0.02). Multivariable Cox regression analysis identified
      wire-based ADR (STAR and LAST) and total stent length as independent predictors
      of MACE. CONCLUSIONS: In this multicenter cohort of patients undergoing CTO PCI
      with ADR techniques, STAR had lower success rates, as compared with the
      CrossBoss/Stingray system and LAST. The CrossBoss/Stingray system was
      independently associated with lower risk of MACE on follow-up, as compared with
      wire-based ADR techniques.

PMID- 27887800
TI  - Coronary artery disease and lunar catecholamine cardiomyopathy.
AB  - OBJECTIVE: Show how lunar catecholamine cardiomyopathy alone, exemplified by Neil
      Armstrong's single space walk, prior to exposure to inhalation of fine
      particulate matter, can trigger " Neil Armstrong Syndrome" or by Irwin with
      coronary, possibly hypertensive heart disease, and catecholamine cardiomyopathy.
      With space flight, invariably magnesium ion deficits, catecholamine elevations,
      vicious cycles. Design Use lunar heart rates while configuring rover to show
      severe tachycardia component of the syndrome. Use Irwin's stress test-" cyanotic
      fingernails" to support Apollo 15 Space Syndrome. Use Irwin's autobiography to
      compensate for often incomplete data. Results Paper shows that both Irwin as well
      as Armstrong meet criteria of my 2nd. Space Syndrome: severe thirst, severe
      shortness of breath, severe tachycardia, the latter, corrected by replenishing
      plasma volume. Conclusions Irwin, with a history of hypertension prior to the
      Apollo 15 mission and classical angina during Earth reentry, may have had
      coronary as well as hypertensive heart disease whereas there was no evidence that
      Armstrong had these conditions prior or during his mission. However both, on
      return to Earth, had abnormal stress tests.

PMID- 27887801
TI  - Cardio-cerebrovascular disease and Helicobacter pylori-related metabolic
      syndrome: We consider eradication therapy as a potential cardio-cerebrovascular
      prevention strategy.

PMID- 27887803
TI  - Reply to the letter to the editor "Survival after cardiac arrest in Greece".

PMID- 27887802
TI  - Meta-analysis of clopidogrel pretreatment in acute coronary syndrome patients
      undergoing invasive strategy.
AB  - BACKGROUND: It is unknown whether pretreatment with clopidogrel in acute coronary
      syndrome (ACS) managed invasively, is superior to a strategy of administering
      clopidogrel in the cardiac catheterization laboratory at the time of percutaneous
      coronary intervention (PCI). Current practice guidelines do not endorse one
      strategy over the other. METHODS: A comprehensive literature search was done to
      identify all relevant studies comparing pretreatment with clopidogrel to
      administration in the cardiac catheterization laboratory at the time of PCI (no
      pretreatment). A meta-analysis using a random effects model was used to calculate
      outcomes of interest. RESULTS: Our search identified 16 studies including 61,517
      ACS patients undergoing cardiac catheterization. At 30days, clopidogrel
      pretreatment was associated with lower MACE 7.67% vs 9.46% (odds ratio (OR) 0.77,
      95% confidence interval (CI) [0.68, 0.86]; P<0.0001) and all-cause mortality 2.8%
      vs 4.1% (OR 0.70, 95% CI [0.58, 0.85]; P=0.0003). Mortality according to the
      longest follow up available was also significantly lower with pretreatment. No
      difference in major bleeding events was observed. These results were not
      significantly different between randomized vs observational studies or STEMI vs
      NSTEACS patients. Sensitivity analysis showed significantly lower MACE 7.98% vs
      9.6% (OR 0.83, 95% CI [0.71, 0.96]; P=0.01) without increased major bleeding in
      NSTEACS patients undergoing PCI within 48h from pretreatment. CONCLUSION: In ACS
      patients undergoing PCI, clopidogrel pretreatment was associated with
      significantly lower 30day all-cause mortality and major adverse cardiovascular
      events without increased major bleeding events.

PMID- 27887804
TI  - The effect of photobiomodulation on chemotherapy-induced peripheral neuropathy: A
      randomized, sham-controlled clinical trial.
AB  - BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side
      effect of cancer therapy with few efficacious treatments. METHODS: We enrolled 70
      patients with CIPN in a randomized, double-blinded, sham-controlled, cross-over
      trial to determine if photobiomodulation (PBM)+/-physiotherapy reduced the
      symptoms of neuropathy compared to sham treatment. At the conclusion of follow
      up, sham-arm patients could cross-over into a third arm combining PBM and
      physiotherapy to determine if multimodal treatment had additive effects.
      Treatment included 30minute sessions 3-times weekly for 6weeks using either PBM
      or sham therapy. Neuropathy was assessed using the modified total neuropathy
      score (mTNS) at initiation and 4, 8, and 16weeks after initiating treatment.
      RESULTS: Sham-treated patients experienced no significant change in mTNS scores
      at any point during the primary analysis. PBM patients experienced significant
      reduction in mTNS scores at all time points. Mean changes in mTNS score (and
      corresponding percent drop from baseline) for sham and PBM-group patients
      respectively were -0.1 (-0.7%) and -4.2 (-32.4%) at 4weeks (p<0.001), 0.2 (0.0%)
      and -6.8 (-52.6%) at 8weeks (p<0.001), and 0.0 (0.1%) and -5.0 (-38.8%) at
      16weeks (p<0.001). Patients who crossed over into the PBM/PT-group experienced
      similar results to those treated primarily; changes in mTNS score from baseline
      were -5.5 (-40.6%) 4weeks (p<0.001), -6.9 (-50.9%) at 8weeks (p<0.001), and -4.9
      (-35.9%) at 16weeks (p<0.001). The addition of physiotherapy did not improve
      outcomes over PBM alone. CONCLUSION AND RELEVANCE: Among patients with CIPN, PBM
      produced significant reduction in neuropathy symptoms.

PMID- 27887805
TI  - Patterns of care of IMRT usage in postoperative management of uterine cancer.
AB  - OBJECTIVE: To analyze the patterns of care regarding intensity modulated
      radiation therapy (IMRT) usage in the postoperative management of uterine cancer.
      METHODS: The National Cancer Database was queried to identify women with
      endometrial adenocarcinoma who underwent hysterectomy followed by external beam
      radiation between 2004-2012. Descriptive statistics were used to analyze IMRT
      usage with comparison via the Chi Square test. Overall survival was also compared
      between IMRT and three dimensional conformal radiation therapy. Multivariable
      logistic regression and multivariable Cox Regression were used to identify
      covariables that impact IMRT usage and improved survival respectively. RESULTS:
      7839 women were included in this study. IMRT utilization increased from 1.9% in
      2004 to 32.4% in 2012 (p<0.001). The adjusted odds ratio (OR) for IMRT in 2012
      compared with 2004 was 24.90, 95% CI 15.24-40.67 (p<0.001). Aside from year,
      other predictors of IMRT usage on multivariate analysis were positive nodes,
      higher dose, private insurance and higher income. Black race was associated with
      lower IMRT usage compared to Whites with an OR of 0.60, 95% CI 0.44-0.81
      (p=0.001). IMRT was not associated with significantly increased survival (HR
      0.86, 95% CI 0.73-1.01, p=0.06). Black race and positive nodes were associated
      with decreased survival within the group studied whereas private insurance and
      higher income were associated with improved survival. CONCLUSIONS: In this
      hospital-based registry, IMRT has significantly increased in utilization for
      postoperative radiation in uterine cancer between 2004-2012 although not
      resulting in significantly improved survival. Socioeconomic and racial
      disparities exist in the allocation of IMRT usage.

PMID- 27887807
TI  - The role of the pharmacy in the management of bronchial asthma: A literature
      based evaluation.
AB  - OBJECTIVE: Pharmacists play a relevant role in the real-life management of asthma
      because they are a first-line referral for patients. In fact, the role of
      pharmacies has been underlined and evidenced also in guidelines. Nonetheless, the
      true effect of pharmacy-based management of asthma has been assessed in only a
      few studies. We review the available literature on asthma management in a
      territorial pharmacy setting. DATA SOURCES: The literature was searched for the
      keywords pharmacy, bronchial asthma, control, and management. STUDY SELECTIONS:
      The available studies were subdivided into observational and interventional and
      described. RESULTS: Seven observational studies and 14 interventional trials were
      found, involving approximately 20,000 individuals. Most of those studies were
      performed in Europe and Australia. A high proportion of patients had poorly
      controlled asthma in the observational studies. The active involvement of
      pharmacists, in the interventional trials, consistently led to an improvement of
      the quality of life, a better inhalation technique, and a reduction of
      exacerbations. CONCLUSION: The literature analysis confirms the relevance of the
      role of pharmacists in the real-life management of bronchial asthma and
      underlines the need for a more specific training for those health care
      professionals.

PMID- 27887806
TI  - A comparison of two psychological interventions for newly-diagnosed gynecological
      cancer patients.
AB  - OBJECTIVE: This study compared the efficacy of two psychological interventions, a
      coping and communication-enhancing intervention (CCI) and supportive counseling
      (SC), in reducing depressive symptoms, cancer-specific distress, fear of
      recurrence, and emotional well-being of women diagnosed with gynecological
      cancer. Demographic, medical, and psychological moderators of intervention
      effects were evaluated. METHODS: Three hundred fifty-two women with gynecological
      cancer were randomly assigned to eight sessions of CCI, eight sessions of SC, or
      usual care (UC). Participants completed measures of distress and wellbeing at six
      time points over an 18month period of time. RESULTS: CCI had a beneficial impact
      on depressive symptoms and cancer specific distress over the first six months as
      compared with UC and SC and had a beneficial impact on emotional well-being. The
      greater coping skill development in CCI has made it a more effective intervention
      than traditional SC across a broader range of key psychological outcomes.
      Declines among women in the SC condition were not significantly different from
      UC. CONCLUSIONS: The CCI intervention had significant effect on patients'
      depression, cancer-specific distress, and emotional well-being during a time when
      the majority of newly diagnosed patients experience elevated levels of distress.
      Ameliorating such distress post-diagnosis merits its incorporation into clinical
      care. A brief 8-session structured intervention can be readily applied to this
      distressed population in need. Brief supportive counseling did not evidence
      treatment effects, suggesting that more structured approaches are crucial to
      truly deliver benefits.

PMID- 27887809
TI  - An estimation of burden of serious fungal infections in France.
AB  - OBJECTIVE OF THE STUDY: An estimation of burden of serious fungal diseases in
      France is essential data to inform public health priorities on the importance of
      resources and research needed on these infections. In France, precise data are
      available for invasive fungal diseases but estimates for several other diseases
      such as chronic and immunoallergic diseases are by contrast less known. MATERIALS
      AND METHODS: A systematic literature search was conducted using the Web of
      Science Platform. Published epidemiology papers reporting fungal infection rates
      from France were identified. Where no data existed, we used specific populations
      at risk and fungal infection frequencies in those populations to estimate
      national incidence or prevalence, depending on the condition. RESULTS: The model
      predicts high prevalences of severe asthma with fungal sensitization episodes
      (189 cases/100,000 adults per year), of allergic bronchopulmonary aspergillosis
      (145/100,000) and of chronic pulmonary aspergillosis (5.24/100,000). Besides,
      estimated incidence for invasive aspergillosis is 1.8/100,000 annually based on
      classical high risk factors. Estimates for invasive mucormycosis, pneumocystosis
      and cryptococcosis are 0.12/100,000, 1/100,000 and 0.2/100,000, respectively.
      Regarding invasive candidiasis, more than 10,000 cases per year are estimated,
      and a much higher number of recurrent vaginal candidiasis is probable but must be
      confirmed. Finally, this survey was an opportunity to report a first picture of
      the frequency of tinea capitis in France. CONCLUSION: Using local and literature
      data of the incidence or prevalence of fungal infections, approximately 1,000,000
      (1.47%) people in France are estimated to suffer from serious fungal infections
      each year.

PMID- 27887811
TI  - Using the Borg CR10 Physical Exertion Scale to Measure Patient-perceived Vocal
      Effort Pre and Post Treatment.
AB  - OBJECTIVES: Reduction of vocal effort is a therapeutic goal in resonant voice
      therapy and in the treatment of a variety of voice disorders. The Borg CR10 is a
      perceived effort scale that is widely accepted across a wide variety of
      disciplines. The purpose of the present study was to examine (1) the utility of
      an anchored, adapted Borg CR10 in observing treatment-related vocal effort
      reduction and (2) the convergent validity of the Borg CR10 in its relation to
      Voice Handicap Index (VHI) item 14. STUDY DESIGN: This is a pretest-posttest
      experimental design. METHODS: A total of 36 individuals with phonotraumatic
      hyperfunctional voice disorders completed item 14 of the VHI and the Borg CR10 at
      the start and completion of four sessions of resonant voice therapy treatment.
      RESULTS: Scores from the Borg CR10 significantly differentiated pre- from post
      therapy perceived effort levels. Convergent validity was demonstrated through
      significant associations with scores from item 14 of the VHI. CONCLUSION: The
      anchored Borg CR10 is an easy to use clinical tool to capture treatment-related
      vocal effort reduction. Whereas VHI item 14 indicates how frequently increased
      perceived effort is experienced, the Borg CR10 captures the severity of perceived
      effort used. Thus, the two measures complement each other.

PMID- 27887810
TI  - Early surgery in infective endocarditis: Why should we wait?

PMID- 27887808
TI  - Norovirus Regulation by Host and Microbe.
AB  - Norovirus (NoV) infection is the leading cause of epidemic gastroenteritis
      globally, and can lead to detrimental chronic infection in immunocompromised
      hosts. Despite its prevalence as a cause of diarrheal illness, the study of human
      NoVs (HNoVs) has historically been limited by a paucity of models. The use of
      murine NoV (MNoV) to interrogate mechanisms of host control of viral infection
      has facilitated the exploration of different genetic mouse models, revealing
      roles for both innate and adaptive immunity in viral regulation. MNoV studies
      have also recently identified important interactions between the commensal
      microbiota and NoV with clear extensions to HNoVs. In this review, we discuss the
      most current understanding of how the host, the microbiome, and their
      interactions regulate NoV infections.

PMID- 27887812
TI  - Chlorobenzene degeradation by non-thermal plasma combined with EG-TiO2/ZnO as a
      photocatalyst: Effect of photocatalyst on CO2 selectivity and byproducts
      reduction.
AB  - The non-thermal plasma (NTP) technique, which suffers from low selectivity in
      complete oxidation of volatile organic compounds to CO2 and H2O, creates unwanted
      and harmful byproducts. NTP in concert with photocatalyst can resolve this
      limitation due to additional oxidation. TiO2 and ZnO nanoparticles were coated on
      the surface of the expanded graphite and placed downstream of the NTP reactor
      under UV light. In this study, to compare the performance of NTP and the combined
      system, chlorobenzene removal, selectivity of CO2 and byproducts formation were
      investigated. The results showed that the combined system enhanced both the
      removal efficiency and CO2 selectivity. The output gas of the NTP reactor
      contained chlorobenzene, phosgene, O3, NO, NO2, CO, CO2, HCL and CL. The bulk of
      these byproducts was oxidized on the surface of the nanocomposite; as a result,
      the content of the byproducts in the output gas of the combined system decreased
      dramatically. The removal efficiency and CO2 selectivity increased by rising the
      applied voltage and residence time because the collision between active species
      and pollutant molecules increases. Based on these results, the combined system is
      preferred due to a higher performance and lower formation of harmful byproducts.

PMID- 27887813
TI  - Migration of 75Se(IV) in crushed Beishan granite: Effects of the iron content.
AB  - The diffusion of selenite (labeled with 75Se) in compacted Beishan granite (BsG)
      was investigated using the in-diffusion capillary method at pH values from ~2.0
      to ~11.0 under oxic and anoxic conditions. The results indicate that the apparent
      diffusion coefficient (Da) values of selenite in BsG always reached the minimum
      at approximately pH 5. Unexpectedly, the Da values under oxic conditions are
      nearly one order of magnitude lower than those under the anoxic conditions.
      Further characterization reveals the existence of redox-sensitive Fe(II)
      containing components, which can be responsible for the great difference in Da
      values. Fe(2p) X-ray photoelectron spectroscopy (XPS) results show that more
      Fe(III)-oxyhydroxide coating is formed on the granite's surface under aerobic
      conditions than is formed under anaerobic conditions. Correspondingly, Se(3d)
      spectra indicate that more selenium is sorbed under oxic conditions, and the
      sorbed amount always reached the maximum at pH values from ~4 to ~5. A linear
      combination fit of X-ray absorption near edge structure (XANES) spectroscopy data
      revealed that Se(0) was formed under anoxic condition and that selenite preferred
      to form inner-sphere complexes with Fe(III)-oxyhydroxide. Overall, this study
      indicates that natural Fe-bearing minerals can greatly attenuate selenite
      diffusion and the retardation would be enhanced under aerobic conditions.

PMID- 27887814
TI  - Effect of bromide on the transformation and genotoxicity of octyl-dimethyl-p
      aminobenzoic acid during chlorination.
AB  - Octyl-dimethyl-p-aminobenzoic acid (ODPABA), one of the most commonly used
      organic UV filters, can undergo considerable transformation in water when
      entering into the disinfection process. The impacts of bromide on degradation
      kinetics, formation and speciation of transformation products, regulated
      disinfection by-products (DBPs) as well as genotoxicity changes during ODPABA
      chlorination were investigated in this study. Results indicated that the reaction
      of ODPABA with chlorine followed pseudo-first-order and second-order kinetics.
      Adding bromide noticeably enhanced the degradation rate of ODPABA, but reduced
      the impact of chlorine dose. Four halogenated transformation products (Cl-ODPABA,
      Br-ODPABA, Cl-Br-ODPABA and Br2-ODPABA) were detected by LC-MS/MS. Mono
      halogenated products were stable during 24-h chlorination, while di-halogenated
      products constantly increased. The total yields of trihalomethanes (THMs) and
      haloacetic acids (HAAs) were both low, but predominated by bromine substitution
      at high levels of bromide. In addition, SOS/umu tests showed that genotoxicity
      was generated after ODPABA chlorination, which was increased at least 1.5 times
      in the presence of bromine. Whereas, no significant genotoxicity variation was
      observed following bromide concentration change.

PMID- 27887815
TI  - Recycled hierarchical tripod-like CuCl from Cu-PCB waste etchant for lithium ion
      battery anode.
AB  - Hierarchical CuCl with high economic value added (EVA) was successfully recycled
      with 85% recovery from the acid Cu printed circuit board (Cu-PCB) waste etchant
      via facile liquid chemical reduction. The micro-structure and morphology of the
      recycled hierarchical CuCl were systematically characterized in terms of scanning
      electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray
      diffraction (XRD), transmission electron microscopy (TEM) and Brunauer-Emmett
      Teller (BET). Furthermore, the corresponding electrochemical performances as
      lithium ion battery (LIB) anode were also investigated in terms of galvanostatic
      charge/discharge, cyclic voltammetry (CV) and AC impedance. As expected, the
      recycled CuCl displayed a hierarchical tripod-like structure and large specific
      surface area of 21.2m2/g. As the anode in LIB, the reversible discharge capacity
      was about 201.4 mAh/g even after 100 cycles, implying the satisfactory cycle
      performance. Clearly, the satisfactory results may open a new avenue to develop
      the sustainable industry, which is very important in terms of both the resource
      recovery and the environmental protection.

PMID- 27887816
TI  - Accelerating biodegradation of a monoazo dye Acid Orange 7 by using its
      endogenous electron donors.
AB  - Biodegradation of a monoazo dye - Acid Orange 7 (AO7) was investigated by using
      an internal circulation baffled biofilm reactor. For accelerating AO7
      biodegradation, endogenous electron donors produced from AO7 by UV photolysis
      were added into the reactor. The result shows that AO7 removal rate can be
      accelerated by using its endogenous electron donors, such as sulfanilic and
      aniline. When initial AO7 concentration was 13.6mg/L, electron donors generated
      by 8h UV photolysis were added into the same system. The biodegradation rate
      0.4mg0.05h-1 was enhanced 60% than that without adding electron donor.
      Furthermore, sulfanilic and aniline were found to be the main endogenous electron
      carriers, which could accelerate the steps of the azo dye biodegradation.

PMID- 27887817
TI  - Is there a role for regenerative medicine in chronic rhinosinusitis with nasal
      polyps?

PMID- 27887818
TI  - Three-Dimensional Morphology of the Left Ventricular Outflow Tract: Impact on
      Grading Aortic Stenosis Severity.
AB  - BACKGROUND: Left ventricular outflow tract (LVOT) measurement is a critical step
      in the quantification of aortic valve area. The assumption of a circular
      morphology of the LVOT may induce some errors. The aim of this study was to
      assess the three-dimensional (3D) morphology of the LVOT and its impact on
      grading aortic stenosis severity. METHODS: Fifty-eight patients with aortic
      stenosis were studied retrospectively. LVOT dimensions were measured using 3D
      transesophageal echocardiography at three levels: at the hinge points (HP) of the
      aortic valve and at 4 and 8 mm proximal to the annular plane. Results were
      compared with standard two-dimensional echocardiographic measurements. RESULTS:
      Three-dimensional transesophageal echocardiography showed a funnel shape that was
      more circular at the HP and more elliptical at 4 and 8 mm proximal to the annular
      plane (circularity index = 0.92 vs 0.83 vs 0.76, P < .001). Cross-sectional area
      was smaller at the HP and larger at 4 and 8 mm from the annular plane (3.6 vs 3.9
      vs 4.1 cm2, P = .001). The best correlation between two-dimensional and 3D
      transesophageal echocardiographic dimensions was at the HP (intraclass
      correlation coefficient = 0.75; 95% CI, 0.59-0.86). When the HP approach was
      selected, there was a reduction in the percentage of patients with low flow (from
      41% to 29%). CONCLUSIONS: A large portion of patients with aortic stenosis have
      funnel-shaped and elliptical LVOTs, a morphology that is more pronounced in the
      region farther from the annular plane. Two-dimensional LVOT measurement closer to
      the annular plane has the best correlation with 3D measurements. Measurement of
      the LVOT closer to the annular plane should be encouraged to reduce measurement
      errors.

PMID- 27887819
TI  - Spontaneous splenic rupture from Plasmodium ovalae malaria.

PMID- 27887820
TI  - Real-time tidal volume feedback guides optimal ventilation during simulated CPR.
AB  - PURPOSE: We performed this study to investigate whether real-time tidal volume
      feedback increases optimal ventilation and decreases hyperventilation during
      manikin-simulated cardiopulmonary resuscitation (CPR). BASIC PROCEDURES: We
      developed a new real-time tidal volume monitoring device (TVD) which estimated
      tidal volume in real time using a magnetic flowmeter. The TVD was validated with
      a volume-controlled mechanical ventilator with various tidal volumes. We
      conducted a randomized, crossover, manikin-simulation study in which 14
      participants were randomly divided into a control (without tidal volume feedback,
      n = 7) and a TVD group (with real-time tidal volume feedback, n = 7) and
      underwent manikin simulation. The optimal ventilation was defined as 420-490 mL
      of tidal volumes for a 70-kg adult manikin. After 2 weeks of the washout period,
      the simulation was repeated via the participants' crossover. MAIN FINDINGS: In
      the validation study, 97.6% and 100% of the difference ratios in tidal volumes
      between the mechanical ventilator and TVD were within +/-1.5% and +/-2.5%,
      respectively. During manikin-simulated CPR, TVD use increased the proportion of
      optimal ventilation per person. Its median values (range) of the control group
      and the TVD group were 37.5% (0.0-65.0) and 87.5% (65.0-100.0), respectively, P <
      .001). TVD use also decreased hyperventilation. The proportions of
      hyperventilation in the control group and the TVD group were 25.0% vs 8.9%,
      respectively (P < .001). PRINCIPAL CONCLUSIONS: Real-time tidal volume feedback
      using the new TVD guided the rescuers to provide optimal ventilation and to avoid
      hyperventilation during manikin-simulated CPR.

PMID- 27887821
TI  - [Sleep disorders in Internet addiction].
AB  - BACKGROUND: The relationship between sleep disorders and Internet addiction has
      been little work. Given the importance of these disorders, we felt it appropriate
      to make a synthesis of available data and to establish causality or
      accountability between Internet addiction and the onset of sleep disorders.
      METHODS: A literature review was then performed. We selected scientific articles
      in English and French, published between 1987 and 2016 by consulting the
      databases Medline, Embase, PsycINFO and Google Scholar. The words used alone or
      in combination are as follows: addiction, dependence, Internet, behavioral
      addiction, sleep. RESULTS: A computer screen light inhibits melatonin secretion
      and acts as a real external desynchronizer circadian rhythm resulting in a
      withdrawal syndrome or syndrome sleep phase delay when the stress of social
      awakening is suppressed. CONCLUSION: We assume here that the specific treatment
      of addictive disorders have an influence on sleep disorders.

PMID- 27887822
TI  - Decline of trace metal pollution in the bottom sediments of the Barcelona City
      continental shelf (NW Mediterranean).
AB  - The evolution of trace metal pollution on the Barcelona city continental shelf
      during the last few decades was studied by analyzing the historical records of
      trace metals in sediment cores and surface sediment samples taken at the same
      locations in 1987 and in 2008. Polluted surface samples taken in 1987 reached
      enrichment factors of up to 490 for Hg, about 40 for Pb and Cd, and about 17 for
      Zn, Cr and Cu. The data show a decline of up to one order of magnitude in the
      trace metal content of surface sediments during the last few decades, with
      maximum enrichment factors of between 20 and 30 for Hg and Cd and between 5 and
      12 for Zn, Cr, Pb and Cu. Although present-day pollution is still significant, it
      is evident that environmental regulations that are in place, including the
      operation since 1979 of wastewater treatment plants built in the Besos River
      watershed, have drastically reduced the pollution levels in this highly populated
      and industrialized Mediterranean area. However, water discharge during heavy rain
      events exceeds the treatment capacity of the existing facilities, leading to the
      maintenance of still high levels of metals in sediments of the Barcelona city
      shelf.

PMID- 27887823
TI  - Transport and transformation of soil-derived CO2, CH4 and DOC sustain CO2
      supersaturation in small boreal streams.
AB  - Streams are typically supersaturated in carbon dioxide (CO2) and methane (CH4),
      and are recognized as important components of regional carbon (C) emissions in
      northern landscapes. Whereas there is consensus that in most of the systems the
      CO2 emitted by streams represents C fixed in the terrestrial ecosystem, the
      pathways delivering this C to streams are still not well understood. We assessed
      the contribution of direct soil CO2 injection versus the oxidation of soil
      derived dissolved organic C (DOC) and CH4 in supporting CO2 supersaturation in
      boreal streams in Quebec. We measured the concentrations of CO2, CH4 and DOC in
      43 streams and adjacent soil waters during summer base-flow period. A mass
      balance approach revealed that all three pathways are significant, and that the
      mineralization of soil-derived DOC and CH4 accounted for most of the estimated
      stream CO2 emissions (average 75% and 10%, respectively), and that these
      estimated contributions did not change significantly between the studied low
      order (<=3) streams. Whereas some of these transformations take place in the
      channel proper, our results suggest that they mainly occur in the hyporheic zones
      of the streams. Our results further show that stream CH4 emissions can be fully
      explained by soil CH4 inputs. This study confirms that these boreal streams, and
      in particular their hyporheic zones, are extremely active processors of soil
      derived DOC and CH4, not just vents for soil produced CO2.

PMID- 27887824
TI  - Reconstructing a long-term record of microcystins from the analysis of lake
      sediments.
AB  - Based on an analysis of sediment cores from Baptiste Lake (Alberta, Canada), we
      quantified century-scale trends in cyanobacteria and cyanotoxins, and identified
      possible drivers of toxigenic cyanobacteria. We measured concentrations of
      microcystins and pigments preserved in the sediment as proxies of toxigenic
      cyanobacteria and phytoplankton communities, respectively, while fossil diatom
      assemblages were used to infer past nutrient concentrations. Microcystins were
      detected in older sediments (ca. 1800s), pre-dating any significant alteration to
      the watershed. This demonstrates that toxigenic cyanobacteria may not be a recent
      phenomenon in eutrophic ecosystems. The dominant variants of microcystin
      throughout the sediment core were microcystin-LA and microcystin-LR. Other
      congeners including -LY, -7dmLR, -WR, -LF, -YR, and -LW (-RR was not detected)
      were mainly found in the upper layers of sediment (post 1980s). Starting in the
      1990s, concentrations of microcystins both in the water column and in the
      sediment record increased in parallel. Total sediment microcystins were strongly
      correlated with historical nitrogen and phosphorus concentrations inferred from
      diatom assemblages (r=0.80-0.81, p<0.001, n=22); both nutrients increased over
      the past two decades coincident with the intensification of agriculture.
      Microcystins also tracked the rise in cyanobacterial pigments present throughout
      the core. In contrast, we found no relationship between climate-related variables
      and sediment microcystin concentrations, although such relationships were
      detected over the monitoring record with respect to water column concentrations.
      Overall, the rise in sediment microcystins was much greater than the rise in
      sediment cyanobacteria and diatom inferred nutrient concentrations. Furthermore,
      we demonstrate that the reconstruction of the microcystin sediment record can
      provide important insight for the development of realistic lake management goals.
      Applying this analytical approach to different lakes and regions of the world,
      where both natural and anthropogenic gradients vary, has the potential to
      markedly improve our understanding of long-term drivers of cyanotoxin production.

PMID- 27887825
TI  - National investigation of semi-volatile organic compounds (PAHs, OCPs, and PCBs)
      in lake sediments of China: Occurrence, spatial variation and risk assessment.
AB  - In this study, a large scale investigation of semi-volatile organic compounds
      (SVOCs) in sediments from 52 lakes, located in five geographic regions across
      China, was conducted to assess sediment quality in terms of organic contaminants.
      Concentrations of polycyclic aromatic hydrocarbons (PAHs), organochlorine
      pesticides (OCPs), and polychlorinated biphenyls (PCBs) in sediment were found to
      range between 17.00-6,633, 0.12-45.24, and 0.03-13.99ngg-1, respectively. Lake
      sediments from different regions exhibited variation in contamination levels, and
      in the compositions of isomers. The descending order of contamination levels for
      the three SVOCs groups (i.e., ?PAHs, ?OCPs, ?PCBs) were as follows: the eastern
      plain region (EPR)>the Yunnan-Guizhou plateau (YGP)>the northeast China region
      (NCR)>the Qinghai-Tibet plateau (QTP)>the Mongolia-Xinjiang plateau (MXP). High
      molecular weight PAHs, OCPs and PCBs were found at high concentrations in parts
      of the EPR and YGP, while lighter isomers were likely to be atmospherically
      transported, resulting in their nationwide distribution. The sources and type
      variation (local input or atmospheric deposition) are the primary controls of
      spatial variation. Additionally, human related socio-economic factors, and
      geographic conditions also played important roles in influencing the spatial
      differentiation. According to simple sediment quality guidelines (SQG), the risks
      posed by PCBs in sediments were not as serious as those posed by PAHs and DDT.

PMID- 27887826
TI  - The impact of droughts and climate change on sinkhole occurrence. A case study
      from the evaporite karst of the Fluvia Valley, NE Spain.
AB  - This work introduces the concept that sinkhole frequency in some karst settings
      increases during drought periods. This conception is tested in a sector of the
      Fluvia River valley in NE Spain, where subsidence phenomena is related to the
      karstification of folded Eocene evaporite formations. In the discharge areas, the
      evaporites behave as confined aquifers affected by hypogene karstification caused
      by aggressive artesian flows coming form an underlying carbonate aquifer. A
      sinkhole inventory with chronological data has been constructed, revealing
      temporal clusters. Those clusters show a good correlation with drought periods,
      as revealed by precipitation, river discharge and piezometric data. This temporal
      association is particularly obvious for the last and current drought starting in
      1998, which is the most intense of the record period (1940-present). Climatic
      projections based on recent studies foresee an intensification of the droughts in
      this sector of NE Spain, which could be accompanied by the enhancement of the
      sinkhole hazard and the associated risks.

PMID- 27887827
TI  - Groundwater resource vulnerability and spatial variability of nitrate
      contamination: Insights from high density tubewell monitoring in a hard rock
      aquifer.
AB  - Agriculture has been increasingly relying on groundwater irrigation for the last
      decades, leading to severe groundwater depletion and/or nitrate contamination.
      Understanding the links between nitrate concentration and groundwater resource is
      a prerequisite for assessing the sustainability of irrigated systems. The
      Berambadi catchment (ORE-BVET/Kabini Critical Zone Observatory) in Southern India
      is a typical example of intensive irrigated agriculture and then an ideal site to
      study the relative influences of land use, management practices and aquifer
      properties on NO3 spatial distribution in groundwater. The monitoring of >200
      tube wells revealed nitrate concentrations from 1 to 360mg/L. Three
      configurations of groundwater level and elevation gradient were identified: i)
      NO3 hot spots associated to deep groundwater levels (30-60m) and low groundwater
      elevation gradient suggest small groundwater reserve with absence of lateral
      flow, then degradation of groundwater quality due to recycling through pumping
      and return flow; ii) high groundwater elevation gradient, moderate NO3
      concentrations suggest that significant lateral flow prevented NO3 enrichment;
      iii) low NO3 concentrations, low groundwater elevation gradient and shallow
      groundwater indicate a large reserve. We propose that mapping groundwater level
      and gradient could be used to delineate zones vulnerable to agriculture
      intensification in catchments where groundwater from low-yielding aquifers is the
      only source of irrigation. Then, wells located in low groundwater elevation
      gradient zones are likely to be suitable for assessing the impacts of local
      agricultural systems, while wells located in zones with high elevation gradient
      would reflect the average groundwater quality of the catchment, and hence should
      be used for regional mapping of groundwater quality. Irrigation with NO3
      concentrated groundwater induces a "hidden" input of nitrogen to the crop which
      can reach 200kgN/ha/yr in hotspot areas, enhancing groundwater contamination.
      Such fluxes, once taken into account in fertilizer management, would allow
      optimizing fertilizer consumption and mitigate high nitrate concentrations in
      groundwater.

PMID- 27887828
TI  - Occupational health risk assessment and exposure to floor dust PAHs inside an
      educational building.
AB  - Polycyclic aromatic hydrocarbons (PAHs) settled in floor dust play an important
      role in human health. Although many studies investigated occupational exposure to
      PAHs, no attempts have been made to report PAHs concentrations as well as their
      health risk assessment inside an educational building in Jordan. Therefore, the
      main objective of this study is to report the PAHs concentrations in floor dust
      and evaluate their exposure and health risk inside the Department of Physics of
      the University of Jordan. The total PAHs concentrations ranged from 714 to
      5246ng/g. The high concentrations were observed inside some offices, where
      tobacco smoking took place. One of those offices was previously renovated and
      some petrochemical liquids were used to remove the remaining glue from a previous
      carpet. Interestingly, the PAHs inside these offices were higher than those
      reported inside lecture rooms and the workshop area, where extensive activates of
      heavy machinery and use of petroleum products (such as lubricating oils). This
      implies that the health effects of exposure to tobacco smoking inside small micro
      environmental places that are poorly ventilated can be very harmful. We also made
      a simple exposure and health risk assessment for the ingested dust (hand-to
      mouth) by calculating the Estimated Daily Intake (EDI) and benzo(a)pyrene
      equivalent carcinogenic power (BaPE). The total EDI was less than 3.75ng/kg
      bw/day whereas the BaPE was less than 385ng/g. These values are lower than what
      was reported in some previous studies in Europe and Asia.

PMID- 27887830
TI  - Drugs of abuse and their metabolites in the urban rivers of Beijing, China:
      Occurrence, distribution, and potential environmental risk.
AB  - The occurrence and distribution of five drugs of abuse and their metabolites,
      namely, methamphetamine (METH), amphetamine (AMP), ketamine (KET), ephedrine
      (EPH), and hydroxylimine (HY), were investigated in the surface water in urban
      rivers in Beijing, China. A total of 117 surface water samples were collected
      from the seven rivers in the Beijing urban areas during four different seasons.
      Laboratory analyses revealed that EPH and METH were the most predominant drugs,
      with detection frequency ranging from 94% to 100% and from 65% to 100%,
      respectively. High levels of METH and KET were observed in the center part of the
      urban areas, which was likely associated with the drug abuse and the
      entertainment activities. Seasonal variation of the drug occurrence showed that
      the highest concentration of drugs of abuse was found during winter, which was
      likely due to the high consumption, low temperature, and low water flows during
      the cold weather. By contrast, the concentration and detection frequency of AMP
      and HY were relatively low. Risk assessment by the risk quotient method indicated
      that the five drugs of abuse and their metabolites were not likely to exert
      biological effects on the aquatic ecosystems at current levels in the surface
      water. However, the potential adverse effect of drugs of abuse and their
      metabolites on ecosystem functioning and human health should not be neglected.

PMID- 27887829
TI  - Use of simulated epithelial lung fluid in assessing the human health risk of Pb
      in urban street dust.
AB  - In many urban contexts, non-dietary Pb exposure from street dusts may add to the
      overall exposure burden, and the presence of high total Pb content is well
      documented in urban street dust from across the globe. Given the increasing
      recognition of the potential adverse health effects from both the quantity and
      the chemical and physical composition of the inhaled fraction, and the
      recognition that it is the soluble fraction rather than the total element content
      that has more direct links to health effects, attention has focused in this study
      on the human health risks via this exposure pathway. In order to investigate the
      environmental exposure to Pb from the inhalation of urban street dusts, a newly
      developed in vitro simulated epithelium lung fluid (SELF) has been applied to the
      <10MUm fraction of urban street dusts. In this context, 21 urban street dust
      samples, across five UK cities, were selected based on their high pseudo-total Pb
      content. The work revealed that inhalation bioaccessibility, and hence inhalation
      dose, varied across the cities but was generally found to be low (<10%). Indeed,
      the lung bioaccessibility was far lower (% lung bioaccessibility ranged from 1.2
      to 8.8) than is currently applied in two of the most commonly employed risk
      assessment models i.e. the Integrated Exposure Uptake Biokinetic model (IEUBK,
      USA) and the Contaminated Land Exposure Assessment model (CLEA, UK). The
      estimated inhalation dose (for adults) calculated from the PM10 bioaccessibility
      ranged from 7ngkg-1BWday-1 (Edinburgh) to 1.3ngkg-1BWday-1 (Liverpool). The
      results indicate a low potential inhalation bioaccessibility for Pb in these
      urban street dust samples when modelled using the neutral pH conditions of the
      SELF.

PMID- 27887831
TI  - Long-term Cu stabilization and biomass yields of Giant reed and poplar after
      adding a biochar, alone or with iron grit, into a contaminated soil from a wood
      preservation site.
AB  - A 2-year pot experiment was carried out to examine the aging effect of biochar
      (B), alone or combined with iron grit (Z), on Cu stabilization and plant growth
      in a contaminated soil (964mg Cu kg-1) from a wood preservation site. The
      experiment consisted in 3 soil treatments, either planted with Arundo donax L.
      (Ad) or Populus nigra L. (Pn): (1) untreated Cu-contaminated soil (Ad, Pn); (2)
      Unt+1% (w/w) B (AdB, PnB), and (3) Unt+1% B+1% Z (AdBZ, PnBZ). After 22months,
      the soil pore water (SPW) was sampled and roots and shoots were harvested. The
      SPW compositions at 3 and 22months were compared, showing that the SPW Cu2+
      concentration increased again in the PnB and PnBZ soils. Cultivation of A. donax
      enhanced the dissolved organic matter concentration in the SPW, which decreased
      its Cu2+ concentration but promoted its total Cu concentration in the Ad and AdB
      soils. Adding Z with B reduced both SPW Cu2+ and Cu concentrations in the pots
      cultivated by A. donax and P. nigra as compared to B alone. The B and BZ
      treatments did not enhance root and shoot yields of both plant species as
      compared to the Unt soil but their shoot Cu concentrations were in the range of
      common values.

PMID- 27887832
TI  - Perfluoroalkyl acids (PFAAs) in the Pra and Kakum River basins and associated tap
      water in Ghana.
AB  - Perfluoroalkyl acids (PFAAs) are persistent environmental pollutants that have
      been detected in various media including human serum. Due to concerns regarding
      their bioaccumulation and possible negative health effects, an understanding of
      routes of human exposure is necessary. PFAAs are recalcitrant in many water
      treatment processes, making drinking water a potential source of human exposure.
      This study presents the first report on contamination from PFAAs in river and
      drinking water in Ghana. The targeted PFAAs were perfluoroalkyl carboxylic acids
      (PFCAs) with C4-14 carbon chain and perfluoroalkane sulphonic acids (PFSAs) with
      C6, 8, 10. Five PFAA congeners - PFOA, PFOS, PFHxA, PFDA and PFPeA - were
      commonly detected in river and tap water. The mean concentrations of ?PFAAs in
      the Kakum and Pra Rivers were 281 and 398ng/L, while tap water (supplied from the
      treatment of water from those rivers) contained concentrations of 197 and
      200ng/L, respectively. PFOA and PFOS constituted about 99% of the ?PFAAs. The
      risk quotient (RQ) attributed to drinking of tap water was estimated at 1.01 and
      1.74 for PFOA and PFOS, respectively. For a country that has not produced these
      compounds, the RQs were unexpectedly high, raising concerns particularly about
      contamination from such emerging pollutants in local water sources. The study
      revealed limitations of local tap water treatment in getting rid of these
      emerging pollutants.

PMID- 27887833
TI  - The impact of pollutants from a major northern highway on an adjacent hardwood
      forest.
AB  - Emissions of pollutants from highways can exert multiple stresses on adjacent
      ecosystems. In this study air concentrations of NO2 and throughfall deposition of
      inorganic N (NO3- and NH4+), SO42-, Cl-, base cations and several metals were
      measured in all four seasons along a 1.5km hardwood forest gradient extending
      away from a major highway (Highway 401) in southern Ontario, Canada. Soil and
      lichen chemistry and herbaceous plant and epiphytic lichen species composition
      were measured within the hardwood forest to evaluate impacts of these pollutants.
      Air concentrations of NO2 and deposition of inorganic N, Cl-, base cations and Cu
      and Zn in throughfall were significantly elevated within 100m of the road
      compared with the more distant sites. Concentrations of several pollutants
      including N (and delta15N), Na+, Al and Fe in epiphytic lichen tissue decreased
      with distance from the highway, and epiphytic lichen richness was lower at sites
      within 100m of the road. Despite high throughfall inputs of >15kgNha-1y-1 and
      100kgNa+ha-1y-1 within 33m of the highway, for example, there was no significant
      difference in soil chemistry amongst sites. Plant community composition at sites
      within 80m of the highway differed from sites located further from the road, but
      it is unclear whether differences were due to highway emissions or were a result
      of natural forest edge effects.

PMID- 27887834
TI  - Neonicotinoids and bees: The case of the European regulatory risk assessment.
AB  - Neonicotinoid insecticides are systemic pesticides authorised in Europe since
      1991. From their introduction on the market, they have received significant
      attention from the scientific community, particularly regarding the assessment of
      lethal and sublethal effects on bees. The availability of scientific evidence
      alongside some concerns raised on the bee health led to the development of more
      articulate risk assessment methodologies for pesticides. To support the European
      Commission in its decision-making process, since 2012 EFSA has been requested to
      evaluate the risk to bees posed by the exposure to neonicotinoids. The outcome of
      the EFSA evaluations has been used by risk managers to revise the approval
      conditions of the substances clothianidin, imidacloprid and thiamethoxam and to
      impose severe restrictions on their use. Meanwhile, a number of new studies have
      been carried out. EFSA is evaluating these data in order to further support the
      decision-making process with updated scientific assessments.

PMID- 27887835
TI  - Link practical-oriented research and education: New training tools for a
      sustainable use of plant protection products.
AB  - In the Horizon 2020 work programme 2016-17 it is stated that in 2010, 71% of
      European farm managers were operating on the basis of practical experience only.
      Education levels greatly vary depending on country, farm managers' age and
      gender, or farm structures, and this can hamper innovation. Transition towards a
      more sustainable agriculture requires a renewal and strengthening of the
      technical skills of all the actors involved and - as a consequence - of the
      educational system. The EU Directive on the sustainable use of pesticides (EU,
      128/2009/EC) requires European Member States to develop training activities
      targeting occupational exposure to pesticides. The objective of this study is to
      develop new training tools for operators, addressing the new legal requirements
      and taking into account what is already available. For this reason, the outcomes
      of different European and national research projects developed by the Opera
      Research Centre were used, involving stakeholders in the decision making process,
      but also considering the real behaviours and perceptions of the final users. As a
      result, an e-learning tool able to build personalized training programmes, by
      collecting and integrating existing training material on Plant Protection
      Products use was developed, together with an e-learning course, with the aim to
      help operators, advisors and distributors to get prepared for their national
      certificate test. This work highlights the opportunity to create long-term added
      value through enhanced collaboration between educators and researchers, and
      identifies a common set of priorities that has to be taken into account in order
      to nudge the changes required to achieve a more sustainable use of pesticide and,
      more in general, sustainable development.

PMID- 27887836
TI  - Modelling white-water rafting suitability in a hydropower regulated Alpine River.
AB  - Cultural and recreational river ecosystem services and their relations with the
      flow regime are still poorly investigated. We develop a modelling-based approach
      to assess recreational flow requirements and the spatially distributed river
      suitability for white-water rafting, a typical service offered by mountain
      streams, with potential conflicts of interest with hydropower regulation. The
      approach is based on the principles of habitat suitability modelling using water
      depth as the main attribute, with preference curves defined through interviews
      with local rafting guides. The methodology allows to compute streamflow
      thresholds for conditions of suitability and optimality of a river reach in
      relation to rafting. Rafting suitability response to past, present and future
      flow management scenarios can be predicted on the basis of a hydrological model,
      which is incorporated in the methodology and is able to account for anthropic
      effects. Rafting suitability is expressed through a novel metric, the "Rafting
      hydro-suitability index" (RHSI) which quantifies the cumulative duration of
      suitable and optimal conditions for rafting. The approach is applied on the Noce
      River (NE Italy), an Alpine River regulated by hydropower production and affected
      by hydropeaking, which influences suitability at a sub-daily scale. A dedicated
      algorithm is developed within the hydrological model to resemble hydropeaking
      conditions with daily flow data. In the Noce River, peak flows associated with
      hydropeaking support rafting activities in late summer, highlighting the dual
      nature of hydropeaking in regulated rivers. Rafting suitability is slightly
      reduced under present, hydropower-regulated flow conditions compared to an
      idealized flow regime characterised by no water abstractions. Localized water
      abstractions for small, run-of-the-river hydropower plants are predicted to
      negatively affect rafting suitability. The proposed methodology can be extended
      to support decision making for flow management in hydropower regulated streams,
      as it has the potential to quantify the response of different ecosystem services
      to flow regulation.

PMID- 27887837
TI  - Evaluating the influence of geo-environmental factors on gully erosion in a semi
      arid region of Iran: An integrated framework.
AB  - Despite the importance of soil erosion in sustainable development goals in arid
      and semi-arid areas, the study of the geo-environmental conditions and factors
      influencing gully erosion occurrence is rarely undertaken. As effort to this
      challenge, the main objective of this study is to apply an integrated approach of
      Geographic Object-Based Image Analysis (GEOBIA) together with high-spatial
      resolution imagery (SPOT-5) for detecting gully erosion features at the Kashkan
      Poldokhtar watershed, Iran. We also aimed to apply a Conditional Probability (CP)
      model for establishing the spatial relationship between gullies and the Geo
      Environmental Factors (GEFs). The gully erosion inventory map prepared using
      GEOBIA and field surveying was randomly partitioned into two subsets: (1) part 1
      that contains 70% was used in the training phase of the CP model; (2) part 2 is a
      validation dataset (30%) for validation of the model and to confirm its accuracy.
      Prediction performances of the GEOBIA and CP model were checked by overall
      accuracy and Receiver Operating Characteristics (ROC) curve methods,
      respectively. In addition, the influence of all GEFs on gully erosion was
      evaluated by performing a sensitivity analysis model. The validation findings
      illustrated that overall accuracy for GEOBIA approach and the area under the ROC
      curve for the CP model were 92.4% and 89.9%, respectively. Also, based on
      sensitivity analysis, soil texture, drainage density, and lithology represent
      significantly effects on the gully erosion occurrence. This study has shown that
      the integrated framework can be successfully used for modeling gully erosion
      occurrence in a data-poor environment.

PMID- 27887838
TI  - A mixture toxicity approach to predict the toxicity of Ag decorated ZnO
      nanomaterials.
AB  - Nanotechnology is a rising field and nanomaterials can now be found in a vast
      variety of products with different chemical compositions, sizes and shapes. New
      nanostructures combining different nanomaterials are being developed due to their
      enhancing characteristics when compared to nanomaterials alone. In the present
      study, the toxicity of a nanostructure composed by a ZnO nanomaterial with Ag
      nanomaterials on its surface (designated as ZnO/Ag nanostructure) was assessed
      using the model-organism Daphnia magna and its toxicity predicted based on the
      toxicity of the single components (Zn and Ag). For that ZnO and Ag nanomaterials
      as single components, along with its mixture prepared in the laboratory, were
      compared in terms of toxicity to ZnO/Ag nanostructures. Toxicity was assessed by
      immobilization and reproduction tests. A mixture toxicity approach was carried
      out using as starting point the conceptual model of Concentration Addition. The
      laboratory mixture of both nanomaterials showed that toxicity was dependent on
      the doses of ZnO and Ag used (immobilization) or presented a synergistic pattern
      (reproduction). The ZnO/Ag nanostructure toxicity prediction, based on the
      percentage of individual components, showed an increase in toxicity when compared
      to the expected (immobilization) and dependent on the concentration used
      (reproduction). This study demonstrates that the toxicity of the prepared mixture
      of ZnO and Ag and of the ZnO/Ag nanostructure cannot be predicted based on the
      toxicity of their components, highlighting the importance of taking into account
      the interaction between nanomaterials when assessing hazard and risk.

PMID- 27887839
TI  - Lung bioaccessibility of As, Cu, Fe, Mn, Ni, Pb, and Zn in fine fraction (<20MUm)
      from contaminated soils and mine tailings.
AB  - The present study aims (1) to characterize contaminated soils (n=6) and mine
      tailings samples (n=3) for As, Cu, Fe, Mn, Ni, Pb, and Zn content; and (2) to
      assess elemental lung bioaccessibility in fine fraction (d<20MUm which might
      contribute to airborne particulate matter (PM) and thus be inhaled) by means of
      in vitro tests using Gamble's solution (GS) and an artificial lysosomal fluid
      (ALF). Elemental concentrations were high in the majority of samples,
      particularly for As (up to 2040mg.kg-1), Fe (up to 30.7%), Mn (up to 4360mg.kg
      1), and Zn (up to 4060mg.kg-1); and elemental concentrations (As, Cu, and Ni) in
      the sieved fraction (d<20MUm) obtained from contaminated soils were significantly
      higher than in the bulk fraction (<160MUm). In vitro tests with ALF yielded much
      higher bioaccessibility than tests with GS, and the use of ALF in addition to GS
      is recommended to assess lung bioaccessibility. Bioaccessibility in ALF was high
      for all elements after 2weeks of testing both in terms of concentration (e.g. up
      to 1730mg.kg-1 for As) and percentages (e.g. up to 81% for Pb). The elemental
      solubilization rate generally declined rapidly and continuously with time.
      Similarly, bioaccessibility increased rapidly and tended to reach a plateau with
      time for most samples and metals. However, it is not possible to recommend a
      general testing duration as the solubilization behavior was highly element and
      sample-specific.

PMID- 27887840
TI  - New p-terphenyls from the endophytic fungus Aspergillus sp. YXf3.
AB  - Five new p-terphenyls named prenylterphenyllin D (1), prenylterphenyllin E (2),
      2'-O-methylprenylterphenyllin (3), 4-O-methylprenylterphenyllin (4) and 3'-O
      methylterphenyllin (5) together with seven known compounds (6-12), were isolated
      from cultures of Aspergillus sp. YXf3. The structures of the new compounds were
      elucidated by extensive MS and NMR analyses. The NMR and MS data of 5 is reported
      for the first time, as its structure was listed in SciFinder Scholar with no
      associated reference. Compounds 6 and 7 were distinguished from each other on the
      basis of 2D NMR experiments. Compounds 1, 2, 3 and 8 showed antibacterial
      activities against X. oryzae pv. oryzicola Swings and E. amylovora with the same
      MIC values of 20MUg/mL while 10 exhibited activities against E. amylovora with an
      MIC value of 10MUg/mL.

PMID- 27887841
TI  - Cytotoxic activity, apoptosis induction and structure-activity relationship of 8
      OR-2-aryl-3,4-dihydroisoquinolin-2-ium salts as promising anticancer agents.
AB  - As our continuing research, a series of 2-aryl-8-OR-3,4-dihydroisoquinolin-2-ium
      bromides were evaluated for cytotoxic activity on cancer cells and apoptosis
      induction in the present study. SAR was derived also. Among them, 23 compounds
      showed the higher cytotoxicity on MKN-45 cells with IC50 values of 1.99-11.3MUM
      than a standard anticancer drug cis-platinum (IC50=11.4MUM) or their natural
      model compound chelerythrine (IC50=12.7MUM); 16 compounds possessed the medium to
      high activity on NB4 cells with IC50 values of 1.67-4.62MUM. SAR analysis showed
      that both substitution patterns of the N-aromatic ring and the type of 8-OR
      significantly impact the activity. AO/EB staining and flow cytometry analysis
      with Annexin V/PI double staining showed that the compounds were able to induce
      apoptosis in a concentration-dependent manner. The results above suggested that
      the title compounds are a class of promising compounds for the development of new
      anti-cancer drugs.

PMID- 27887842
TI  - Simple N,N-dimethyl phenylsulfonamides show potent anticonvulsant effect in two
      standard epilepsy models.
AB  - Optimization of the previously reported benzothiazine analogue A led to the
      identification of compound 1, which showed anti-convulsant activity in two golden
      standard animal models of seizure, the MES and scPTZ models. Structure-activity
      relationship investigation of compound 1 revealed compounds 2, 6 and 19 as
      attractive anti-epileptic drug (AED) candidates with potent anticonvulsant effect
      in both the MES and scPTZ models. As these compounds are structurally different
      from existing AEDs, determination of their mechanism of actions could provide
      clues to understanding current therapy-resistant seizures. Moreover, these simple
      phenylsulfoneamide compounds could be good starting points for searching broad
      spectrum AEDs by such in vivo screening.

PMID- 27887843
TI  - Synthesis and bioactivity evaluation of 2,3-diaryl acrylonitrile derivatives as
      potential anticancer agents.
AB  - Thirty novel derivatives of 2,3-diaryl acrylonitrile were synthesized and
      evaluated for biological activity. Preliminary investigations of antitumor
      activity in vitro showed that most of the synthesized compounds have significant
      antiproliferative effects on human cancer cell lines, such as BEL-7402, HeLa, and
      HCT116 with IC50 values in the range of 0.13-60.23MUM without significant toxic
      effects on the non-cancerous human liver cell line L-02. In particular, compounds
      4d and 4p were found to be the most potent against HeLa (4.20MUM) and HCT116
      cells (0.13MUM), respectively, with superior or similar in vitro efficacy to that
      of the broad-spectrum anticancer drug taxol.

PMID- 27887844
TI  - Anthraquinones from Morinda longissima and their insulin mimetic activities via
      AMP-activated protein kinase (AMPK) activation.
AB  - AMP-activated protein kinase (AMPK) activators are known to increase energy
      metabolism and to reduce body weight, as well as to improve glucose uptake.
      During for searching AMPK activators, a new anthraquinone, modasima A (10), along
      with eighteen known analogues (1-9 and 11-19) were isolated from an ethanol
      extract of the roots of Morinda longissima Y. Z. Ruan (Rubiaceae). Using the
      fluorescent tagged glucose analogues, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino)-2-deoxy-D-glucose (2-NBDG), insulin mimetics were screened with
      compounds 1-19 in 3T3-L1 adipocytes. Among them, compounds 2, 8 and 10 enhanced
      significantly glucose uptake into adipocytes and up-regulated the phosphorylated
      AMPK (Thr172) whereas the glucose uptake enhancing activities of compounds 2, 8
      and 10 were abrogated by treatment of compound C, an AMPK inhibitor. Taken
      together, these anthraquinones showed the potential action as insulin mimetic to
      improve glucose uptake via activation of AMPK.

PMID- 27887845
TI  - [Management of atherosclerotic renal-artery stenosis in 2016].
AB  - Endovascular revascularization as treatment of atherosclerotic renal-artery
      stenosis (aRAS) is controversial since 3 large and multicentric randomised trials
      (CORAL, ASTRAL, STAR) failed to prove the superiority of percutaneous
      transluminal renal-artery stenting (PTRAS) over medical treatment only (MT).
      However, considering the multiple bias of these trials, among which questionable
      inclusion criterias, these results must be extrapolated in clinical practice with
      caution. New pathophysiological data have been helping to understand why
      restoring blood flow does not necessarily lead to kidney function improvement.
      Today, the diagnostic approach must in one hand confirm the artery stenosis and
      on the other hand assess its severity and impact on the kidney. Therapeutic
      options still lie on the American guidelines published in 2006, since no study
      data can be reasonably used in everyday practice. However, particular sub-groups
      of patients who could benefit from revascularisation have been identified through
      recent cohort studies. Further prospective studies are needed in order to confirm
      the superiority of PTRAS in these populations. Meanwhile, multidisciplinary
      approach should be promoted, in order to provide the best treatment for each
      patient.

PMID- 27887846
TI  - Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1
      regulates the expression of Gli2 by miR-202 to strengthen gastric cancer
      progression.
AB  - BACKGROUND: Gastric cancer (GC) is one of the most common malignancies and ranks
      the second leading cause of cancer death worldwide. Some studies had reported the
      tumor-promoting effects of long non-coding RNA metastasis-associated lung
      adenocarcinoma transcript 1 (MALAT1) as a competing endogenous RNA (ceRNA) by
      sponging to microRNAs. However, the molecular mechanism of ceRNA regulatory
      pathway involving MALAT1 in GC remains unclear. METHODS: MALAT1 and miR -202
      expression was detected by quantitative real time PCR (qRT-PCR) in 60 gastric
      cancer tissues and adjacent normal tissues, CCK8 cell proliferation assays, cell
      cycle analysis and cell apoptosis assays were performed to detect the GC cell
      proliferation and apoptosis. The mRNA and protein levels of Gli2 were analyzed by
      quantitative real-time PCR and Western blotting assays. Furthermore, using online
      software, luciferase reporter assays, RNA immunoprecipitation (RIP) and RNA
      pulldown assays demonstrated miR-202 was a target of MALAT1. RESULTS: We found
      that MALAT1 was upregulated in GC tissues and higher MALAT1 expression was
      correlated with larger tumor size, lymph node metastasis, and TNM stage.
      Moreover, we revealed that MALAT1 was a direct target of miR-202 and knockdown of
      MALAT1 significantly decreased the expression of Gli2 through negatively
      regulating miR-202. In addition, knockdown of Malat1 inhibited GC cells
      proliferation, S-phase cell number, and induced cell apoptosis via negatively
      regulating miR-202 in vitro. CONCLUSIONS: Our results elucidated MALAT1/miR
      202/Gli2 regulatory pathway, which maybe contribute to a novel therapeutic
      strategy for GC patients.

PMID- 27887847
TI  - Role of the HTLV-1 viral factors in the induction of apoptosis.
AB  - Adult T-cell leukemia (ATL) and HTLV-1-associated Myelopathy/Tropical Spastic
      Paraparesis (HAM/TSP) are the two main diseases that are caused by the HTLV-1
      virus. One of the features of HTLV-1 infection is its resistance against
      programmed cell death, which maintains the survival of cells to oncogenic
      transformation and underlies the viruses' therapeutic resistance. Two main genes
      by which the virus develops cancer are Tax and HBZ; playing an essential role in
      angiogenesis in regulating viral transcription and modulating multiple host
      factors as well as apoptosis pathways. Here we have reviewed by prior research
      how the apoptosis pathways are suppressed by the Tax and HBZ and new drugs which
      have been designed to deal with this suppression.

PMID- 27887848
TI  - Simvastatin inhibits tumor angiogenesis in HER2-overexpressing human colorectal
      cancer.
AB  - Overexpression of the HER2 oncogene contributes to tumor angiogenesis, which is
      an essential hallmark of cancer. Simvastatin has been reported to exhibit
      antitumor activities in several cancers; however, its roles and molecular
      mechanismsin the regulation of colorectal angiogenesis remain to be clarified.
      Here, we show that colon cancer cells express high levels of VEGF, total HER2 and
      phosphorylated HER2, and simvastatin apparently decreased their expression in
      HER2-overexpressing colon cancer cells. Simvastatin pretreatment reduced
      endothelial tube formation in vitro and microvessel density in vivo. Furthermore,
      simvastatin markedly inhibited tumor angiogenesis even in the presence of
      heregulin (HRG)-beta1 (a HER2 co-activator) pretreatment in HER2+ tumor cells.
      Mechanistic investigation showed that simvastatin significantly abrogated HER2
      induced tumor angiogenesis by inhibiting VEGF secretion. Together, these results
      provide a novel mechanism underlying the simvastatin-induced inhibition of tumor
      angiogenesis through regulating HER2/VEGF axis.

PMID- 27887850
TI  - Laser flow cytometry as a tool for the advancement of clinical medicine.
AB  - Flow cytometry is a classic laser technology. With the discovery of the
      cytometer, flow cytometry has become a primary tool in biodiagnostic research.
      This review focuses on current applications of flow cytometry to the diagnosis of
      disease and treatment monitoring at the single-cell level. A description of the
      principles of flow cytometry and a brief overview of the major applications are
      presented. Our criteria for selecting research papers for this review are those
      that show advances in biomedicine and pharmacotherapy achieved by using non
      invasive flow cytometry. New concepts for diagnosis and classification based on
      quantitative measurements of cellular parameters and the expression of specific
      differentiation antigens on the surface of cells will be discussed herein.

PMID- 27887851
TI  - Nonlinear dynamics of avian influenza epidemic models.
AB  - Avian influenza is a zoonotic disease caused by the transmission of the avian
      influenza A virus, such as H5N1 and H7N9, from birds to humans. The avian
      influenza A H5N1 virus has caused more than 500 human infections worldwide with
      nearly a 60% death rate since it was first reported in Hong Kong in 1997. The
      four outbreaks of the avian influenza A H7N9 in China from March 2013 to June
      2016 have resulted in 580 human cases including 202 deaths with a death rate of
      nearly 35%. In this paper, we construct two avian influenza bird-to-human
      transmission models with different growth laws of the avian population, one with
      logistic growth and the other with Allee effect, and analyze their dynamical
      behavior. We obtain a threshold value for the prevalence of avian influenza and
      investigate the local or global asymptotical stability of each equilibrium of
      these systems by using linear analysis technique or combining Liapunov function
      method and LaSalle's invariance principle, respectively. Moreover, we give
      necessary and sufficient conditions for the occurrence of periodic solutions in
      the avian influenza system with Allee effect of the avian population. Numerical
      simulations are also presented to illustrate the theoretical results.

PMID- 27887849
TI  - Inhibition of heat shock protein (Hsp) 90 potentiates the antiproliferative and
      pro-apoptotic effects of 2-(4'fluoro-phenylamino)-4H-1,3-thiazine[6,5-b]indole in
      A2780cis cells.
AB  - Ovarian carcinoma is initially sensitive to platinum-based therapy, but become
      resistant over time. The study of cancer sensitizing substance is therefore the
      major challenge for a number of scientific groups. Our experiments were carried
      out on human ovarian adenocarcinoma A2780cis cells resistant to cisplatin and
      their response to 2-(4'fluoro-phenylamino)-4H-1,3-thiazine[6,5-b]indole
      (thiazine[6,5-b]indole) and/or heat shock protein (Hsp) 90 inhibitor 17
      dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) using proliferation
      assay, cell cycle analysis and monitoring of apoptosis were examined. A2780cis
      cells revealed the same fold of resistance to Hsp90 inhibitor 17-DMAG as it is
      declared for cisplatin (18 times), but only 3.2 times for thiazine[6,5-b]indole.
      Our results showed that the combination of thiazine[6,5-b]indole and 17-DMAG
      significantly reduced proliferation of A2780cis cells and led to their
      accumulation in G2/M phase of the cell cycle. Moreover, both thiazine[6,5
      b]indole as well as 17-DMAG increased the number of annexin V positive A2780cis
      cells in time dependent manner. Interestingly, thiazine[6,5-b]indole treatment
      significantly activated also caspase-3 compared to untreated or 17-DMAG-treated
      cells and reduced mitochondrial membrane potential (MMP) of A2780cis cells with
      more significant decline after combined treatment. In this regard, the incubation
      of A2780cis cells with thiazine[6,5-b]indole induced PARP protein cleavage as
      well as an increased level of Bad protein with more pronounced changes after
      combined treatment. Importantly, Hsp70 protein was not upregulated in A2780cis
      cells neither by individual treatment nor by mutual combination. Our results
      signify antiproliferative and pro-apoptotic effects of novel thiazine[6,5
      b]indole potentiated by Hsp90 inhibitor 17-DMAG in ovarian adenocarcinoma cells
      resistant to cisplatin and therefore represents new strategy in cancer treatment.

PMID- 27887852
TI  - Morphological and functional imaging of neck paragangliomas.
AB  - OBJECTIVE: To review the optimal techniques for localization and characterization
      of neck paragangliomas (PGL). MATERIAL AND METHODS: Systematic review of the
      literature from the PubMed/Medline database. RESULTS: Neck PGL are hypervascular
      tumours essentially arising from paraganglionic tissue situated at the carotid
      bifurcation (carotid body) and along the vagus nerve. Morphological and
      functional imaging are indicated to confirm the diagnosis, identify multifocal
      disease and for local and regional staging. MR angiography is the noninvasive
      technique of choice. CT scan and especially CT angiography are excellent
      alternatives for diagnosis and staging. Conventional arteriography remains useful
      preoperatively for embolization and occlusion tests. Functional imaging allows
      localization and characterization of PGLs. Somatostatin receptor scintigraphy
      (SRS) was the reference imaging technique for staging of sporadic PGLs. The
      indications for PET imaging have been extended over recent years in parallel with
      the development of new tracers such as [18F]-FDOPA PET or 68Gallium-labelled DOTA
      peptides. 68Gallium-labelled DOTA peptides has become the first-line imaging
      modality in the evaluation of cervical PGLs, regardless of the genetic
      background. CONCLUSION: Morphological and functional imaging is essential for the
      staging of neck PGL.

PMID- 27887853
TI  - The value of endografts in the surgical management of arterial lesions secondary
      to Behcet disease.
AB  - BACKGROUND: This study summarizes our experience in the surgical management of
      arterial lesions secondary to Behcet disease (BD) and assesses the value of
      endografts. METHODS: Data from BD patients with arterial lesions managed
      surgically in our center from January 1998 to December 2015 were studied
      retrospectively. Surgical procedures, graft selection, graft-related
      complications, and retreatments were analyzed. RESULTS: We recruited 33 patients
      (29 men and 4 women; male-to-female ratio, 7.25:1) with an average age of 36.7
      years (range, 25-51 years). The arterial lesions included 27 aneurysms in 24
      patients and nine stenotic or occlusive lesions in nine patients.
      Immunosuppressive therapy was administered routinely preoperatively and
      postoperatively as recommended. Altogether, 15 great saphenous veins (GSVs), 8
      synthetic grafts, and 13 endografts were used in 36 primary procedures. The mean
      follow-up duration was 3.8 +/- 2.9 years. Graft-related pseudoaneurysm was seen
      in three GSVs (20%) and in three synthetic grafts (38%) at the anastomosis, but
      not in endograft implantations (log-rank, P = .171). Graft occlusions were
      observed in 1 GSV (7%), 2 synthetic (25%), and 2 endografts (15%; log-rank, P =
      .881). Graft infection occurred in one synthetic graft (13%) and in one endograft
      (8%) but not in the GSVs (log-rank, P = .689). Graft-related artery rupture
      occurred in only one endograft (8%). Two patients died, giving a mortality rate
      of 6.1%. CONCLUSIONS: In the surgical management of arterial lesions secondary to
      BD, endografts were superior to GSV and synthetic grafts in decreasing
      anastomotic pseudoaneurysm. However, improvements are needed to enhance the long
      term patency and reduce infections.

PMID- 27887855
TI  - Regional anesthesia as the anesthetic of choice for high-risk surgical patients
      undergoing repair of juxtarenal aortic aneurysms with fenestrated stent grafts.
AB  - Juxtarenal aortic aneurysms (JAAs) have been conventionally treated using open
      repair with excellent results. Recent approval of fenestrated stent grafts by the
      United States Food and Drug Administration has given patients with JAAs an
      alternative for repair. However, most of these procedures are still performed
      under general anesthesia, making some surgeons reluctant to offer repair to a
      subset of patients deemed too high risk for general anesthesia. We present three
      patients with JAAs at high surgical risk, including one patient with a ruptured
      aneurysm, who were successfully treated using a fenestrated stent graft under
      regional anesthesia.

PMID- 27887854
TI  - Significant regional variation exists in morbidity and mortality after repair of
      abdominal aortic aneurysm.
AB  - OBJECTIVE: Limited data exist comparing perioperative morbidity and mortality
      after open and endovascular abdominal aortic aneurysm (AAA) repair (EVAR) among
      regions of the United States. This study evaluated the regional variation in
      mortality and perioperative outcomes after repair of AAAs. METHODS: The Vascular
      Quality Initiative (VQI) was used to identify patients undergoing open AAA repair
      and EVAR between 2009 and 2014. Ruptured and intact aneurysms were evaluated
      separately, and the analysis of intact aneurysms was limited to infrarenal AAAs.
      All 16 regions of the VQI were deidentified, and those with <100 open repairs
      were combined to eliminate the effect of low-volume regions. Regional variation
      was evaluated using chi2 and Fisher exact tests. Regional rates were compared
      against current quality benchmarks. RESULTS: Perioperative outcomes from 14
      regions were compared. After open repair of intact aneurysms, no significant
      variation was seen in 30-day or in-hospital mortality; however, multiple regions
      exceeded the Society for Vascular Surgery benchmark for in-hospital mortality
      after open repair of intact aneurysms of <5% (range, 0%-7%; P = .55). After EVAR,
      all regions met the Society for Vascular Surgery benchmark of <3% (range, 0%-1%;
      P = .75). Significant variation in in-hospital mortality existed after open (14%
      63%; P = .03) and endovascular (3%-32%; P = .03) repair of ruptured aneurysms
      across the VQI regional groups. After repair of intact aneurysms, wide variation
      was seen in prolonged length of stay (>7 days for open repair: 32%-53%, P = .54;
      >2 days for EVAR: 16-43%, P < .01), transfusion (open: 10%-35%, P < .01; EVAR: 7%
      18%, P < .01), use of vasopressors (open: 19%-37%, P < .01; EVAR: 3%-7%, P <
      .01), and postoperative myocardial infarction (open: 0%-13%, P < .01; EVAR: 0%
      3%, P < .01). After open repair, worsening renal function (6%-18%; P = .04) and
      respiratory complications (6%-20%; P = .20) were variable across regions. The
      frequency of endoleak at completion of EVAR also had considerable variation (15%
      38%; P < .01). CONCLUSIONS: Despite limited variation, multiple regions do not
      meet current benchmarks for in-hospital mortality after open AAA repair for
      intact aneurysms. Significant regional variation exists in perioperative outcomes
      and length of stay, and mortality is widely variable after repair for rupture.
      These data identify important areas for quality improvement initiatives and
      clinical practice guidelines.

PMID- 27887856
TI  - Preoperative thoracic false lumen branches relate to aortic remodeling after
      thoracic endovascular aortic repair for DeBakey IIIb aortic dissection.
AB  - OBJECTIVE: This study evaluated the association between thoracic false lumen
      branches (TFLBs; dissected thoracic branches fed by a false lumen) and distal
      thoracic aortic enlargement (DTAE) after thoracic endovascular aortic repair
      (TEVAR) for DeBakey IIIb aortic dissection. METHODS: We retrospectively analyzed
      the records of 67 patients with DeBakey IIIb dissection initially treated with
      TEVAR between January 2011 and December 2013. Preoperative and postoperative
      computed tomography angiography images were reviewed to evaluate the number of
      preoperative TFLBs and aortic diameter change after TEVAR. Patients were
      stratified into two groups by the estimated optimal cutoff value of preoperative
      TFLBs for the prediction of DTAE: group A (n = 28), preoperative TFLBs >=8; group
      B (n = 39), preoperative TFLBs <8. The diameter changes over time were modeled by
      mixed models of repeated data. Multivariable Cox regression analysis was used to
      assess the independent association between preoperative TFLBs and DTAE after
      TEVAR. RESULTS: Baseline demographics, clinical features, and devices implanted
      were largely similar between the two groups. Group A had more preoperative
      abdominal false lumen branches (7 [4-8] vs 4 [1-6]; P = .02) and a greater
      proportion of preoperative patent thoracic false lumen (83.9% vs 66.7%; P = .04).
      Twelve patients experienced DTAE during a median imaging follow-up period of 12.2
      months (interquartile range, 4.3-26.6 months). Log-rank testing revealed a
      significant increase in cumulative estimated proportion with DTAE in group A (P <
      .01). The maximum thoracic aortic diameter decreased significantly in group B (P
      < .01) but not in group A. The overall change in the maximum thoracic aortic
      diameter was statistically different between the two groups (P < .01). Each group
      exhibited a significant increase in true lumen diameter and a significant
      decrease in false lumen diameter postoperatively. However, a lower degree of
      false lumen regression in group A was detected compared with group B (P = .03).
      Multivariable analysis identified that preoperative TFLBs were independently
      associated with DTAE after TEVAR (hazard ratio [for one increase], 1.46; 95%
      confidence interval, 1.20-1.77) after adjustment for gender, hyperlipidemia,
      length of dissected aorta and height index, preoperative abdominal false lumen
      branches, and preoperative false lumen status of thoracic aorta. CONCLUSIONS:
      Preoperative TFLBs are independently associated with DTAE after TEVAR in DeBakey
      IIIb aortic dissection. Long-term follow-up is necessary to further verify the
      preliminary finding.

PMID- 27887857
TI  - A potential contribution of dipeptidyl peptidase-4 by the mediation of monocyte
      differentiation in the development and progression of abdominal aortic aneurysms.
AB  - OBJECTIVE: Abdominal aortic aneurysms (AAAs) are characterized by the destruction
      of elastin and collagen in the media and adventitia. Dipeptidyl peptidase-4 (DPP
      4, an adipokine known as CD26) influences cell signaling, cell-matrix
      interactions, and the regulation of the functional activity of incretins in
      metabolic and inflammatory disorders. Although the role of DPP-4 in AAA evolution
      has been demonstrated, the underlying mechanisms of DPP-4-regulated AAA
      development remains unknown. METHODS: Patients with AAA (n = 93) and healthy
      controls (CTL, n = 20) were recruited. Based on computed tomography image
      analyses, 93 patients were divided into two groups: those with a small AAA (SAA,
      aortic diameter <5 cm, n = 16) and those with a large AAA (LAA, aortic diameter
      >=5 cm, n = 77). Plasma DPP-4, glucagon-like peptide-1 levels, and expression of
      CD26 on mononuclear cells were analyzed. In addition, phorbol 12-myristate 13
      acetate (PMA)-induced THP-1 cells and angiotensin II-infused apolipoprotein
      EtmlUnc mice were used to explore the underlying mechanisms. RESULTS: The levels
      of DPP-4 (MUU/MUg) increased while active glucagon-like peptide-1 (pM) decreased
      in patients with AAA in a diameter-dependent manner [CTL: 2.3 +/- 1.5 and 3.7 +/-
      2.4, respectively; SAA: 10.0 +/- 10.9 and 2.1 +/- 0.9, respectively; LAA: 32.2 +/
      15.0 and 1.8 +/- 1.1, respectively]. A significant decline in monocyte CD26
      expression in patients with AAAs was observed relative to the CTL group. In vitro
      studies demonstrated that the inhibition of DPP-4 promoted PMA-induced monocytic
      cells differentiation, with increased CD68 and p21 expression, regulated by
      extracellular signal-regulated protein kinase 1/2 activation. Furthermore,
      inhibition of DPP-4 significantly increased the phosphorylation of PYK2 and
      paxillin in PMA-induced THP-1 cell differentiation. Finally, the animal study was
      used to confirm the in vitro results that LAA mice showed marked macrophage
      infiltration in the adventitia with a decreased expression of DPP-4 as compared
      with SAA mice. CONCLUSIONS: Increased plasma DPP-4 activity may correlate with
      aneurysmal development. CD26 on monocytes plays a critical role in cell
      differentiation, possibly mediated by extracellular signal-regulated protein
      kinase 1/2-p21 axis signaling pathways and cytoskeletal proteins reassembly.
      Exploring the role of DPP-4 further may yield potential therapeutic insights.

PMID- 27887858
TI  - Predictive value of neutrophil-to-lymphocyte ratio in diabetic wound healing.
AB  - OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been used as a surrogate
      marker of systemic inflammation. We sought to investigate the association between
      NLR and wound healing in diabetic wounds. METHODS: The outcomes of 120 diabetic
      foot ulcers in 101 patients referred from August 2011 to December 2014 were
      examined retrospectively. Demographic, patient-specific, and wound-specific
      variables as well as NLR at baseline visit were assessed. Outcomes were
      classified as ulcer healing, minor amputation, major amputation, and chronic
      ulcer. RESULTS: The subjects' mean age was 59.4 +/- 13.0 years, and 67 (66%) were
      male. Final outcome was complete healing in 24 ulcers (20%), minor amputation in
      58 (48%) and major amputation in 16 (13%), and 22 chronic ulcers (18%) at the
      last follow-up (median follow-up time, 6.8 months). In multivariate analysis,
      higher NLR (odds ratio, 13.61; P = .01) was associated with higher odds of
      nonhealing. CONCLUSIONS: NLR can predict odds of complete healing in diabetic
      foot ulcers independent of wound infection and other factors.

PMID- 27887859
TI  - Olanzapine modulation of long- and short-range functional connectivity in the
      resting brain in a sample of patients with schizophrenia.
AB  - Treatment effects of antipsychotic drugs on cerebral function are seldom
      examined. Exploring functional connectivity (FC) in drug-free schizophrenia
      patients before and after antipsychotic treatment can improve the understanding
      of antipsychotic drug mechanisms. A total of 17 drug-free patients with recurrent
      schizophrenia and 24 healthy controls underwent resting-state functional magnetic
      resonance imaging scans. Long- and short-range FC strengths (FCS) were calculated
      for each participant. Compared with the controls, the patients at baseline
      exhibited increased long-range positive FCS (lpFCS) in the bilateral inferior
      parietal lobule (IPL) and decreased lpFCS in the brain regions of the default
      mode network (DMN) regions and sensorimotor circuits of the brain. By contrast,
      increased short-range positive FCS was observed in the right IPL of the patients
      at baseline compared with the controls. After treatment with olanzapine,
      increased FC in the DMN and sensorimotor circuits of the brain was noted, whereas
      decreased FC was observed in the left superior temporal gyrus (STG). Moreover,
      the alterations of the FCS values and the reductions in symptom severity among
      the patients after treatment were correlated. The present study provides evidence
      that olanzapine normalizes the abnormalities of long- and short-range FCs in
      schizophrenia. FC reductions in the right IPL may be associated with early
      treatment response, whereas those in the left STG may be related to poor
      treatment outcome.

PMID- 27887860
TI  - Modeling the development of panic disorder with interoceptive conditioning.
AB  - Panic disorder is characterized by the paroxysmal occurrence and fear of bodily
      symptoms. In recent years it has been proposed that patients "learn" to fear
      cardiorespiratory sensations through interoceptive conditioning. This study
      sought to model the initial stage of this process in healthy volunteers (N=44)
      using mild cardiac sensations. An additional aim was to explore whether anxiety
      sensitivity - a known risk factor for panic disorder - modulates such
      interoceptive learning. Infusions of pentagastrin and saline were used to
      manipulate the presence versus absence of cardiac sensations, respectively, and
      served as conditioned stimuli in a differential interoceptive conditioning
      paradigm. Inhalation of 35% CO2-enriched air served as the panicogenic,
      unconditioned stimulus (UCS). In half of the participants ("prepared" condition),
      cardiac sensations caused by pentagastrin were followed by inhalation of CO2
      enriched air (penta CS+), whereas the absence of such sensations (saline) was
      followed by room air (saline CS-). The reversed combination ("unprepared"
      condition) was used in the other half of the participants. Conditioning effects
      showed up for self-reported UCS-expectancy, but not for skin conductance and
      anxiety ratings. Only participants from the prepared group learned to expect the
      UCS, and differential learning was impaired with higher scores on anxiety
      sensitivity. Expectancy learning was more easily established towards the presence
      compared to the absence of cardiac sensations, whereas the reverse effect was
      observed for safety learning. Modeling impaired discriminatory learning and the
      moderating effect of anxiety sensitivity provides new insight in the development
      of panic disorder.

PMID- 27887861
TI  - Bias in the reporting of harms in clinical trials of second-generation
      antidepressants: The tip of the iceberg?
AB  - Serious adverse events are poorly reported in clinical trials of second
      generation antidepressants. Moreover some key opinion leaders (eg. in France)
      deliberately failed to warn against them. The gross distortions of
      antidepressants' benefit:harm ratio in adolescents showed evidence that open
      science (ie access to de-identified individual patient data for re-analyses) is a
      mandatory prerequisite for a trustworthy science.

PMID- 27887862
TI  - Report on the microbiota of Melipona quadrifasciata affected by a recurrent
      disease.
AB  - Melipona quadrifasciata is an eusocial stingless bee traditionally used for honey
      production in Brazil. In the last decades, the species disappeared from the wild
      in Southern Brazil, being kept exclusively in managed colonies for commercial and
      recreational purposes. Stingless beekeepers from this region report annual losses
      of their colonies due to a syndrome of yet unknown causes. We investigate whether
      it is associated to pathogenic microorganisms already known to cause disease in
      bees. These results provide a starting point for future studies aimed at
      clarifying the relationship between the microbial community of stingless bees and
      their colony collapses.

PMID- 27887863
TI  - Body mass index and mortality in patients with type 2 diabetes mellitus: A
      prospective cohort study of 11,449 participants.
AB  - AIMS: To investigate the association between body-mass index and mortality in
      Chinese adults T2DM. METHODS: 11,449 participants of Kailuan Study with T2DM were
      included in this prospective cohort study. All-cause mortality was calculated
      using Kaplan-Meier analysis. Cox proportional hazards analysis was used to
      estimate the association between BMI and mortality. RESULTS: During a mean follow
      up period of 7.25+/-1.42years, 1254 deaths occurred. The number of deaths of the
      underweight, normal weight, overweight, and obese group was 23, 389, 557, and
      285; the corresponding mortality was 25.0%, 13.4%, 10.3%, and 9.4%, respectively.
      The obese group had the lowest all-cause mortality rate (log-rank chi
      square=48.430, P<0.001). After adjusting for age, sex, fasting blood glucose,
      smoking status, systolic blood pressure, history of hypertension, stroke, cancer
      and myocardial infarction, compared with the normal weight group, Multivariate
      Cox proportional hazard regression analysis showed that HR (95% CI) of all-cause
      mortality in the underweight, overweight, and obese group was 1.497 (0.962,
      2.330), 0.833 (0.728, 0.952), and 0.809 (0.690, 0.949). After stratifying for age
      tertiles, this trend remained. CONCLUSIONS: In T2DM patients in north China, the
      risk for all-cause mortality was lower in the overweight and the obese groups
      than those in the normal weight and the underweight groups.

PMID- 27887866
TI  - Continuously expanding CAR NK-92 cells display selective cytotoxicity against B
      cell leukemia and lymphoma.
AB  - BACKGROUND AIMS: Natural killer (NK) cells can rapidly respond to transformed and
      stressed cells and represent an important effector cell type for adoptive
      immunotherapy. In addition to donor-derived primary NK cells, continuously
      expanding cytotoxic cell lines such as NK-92 are being developed for clinical
      applications. METHODS: To enhance their therapeutic utility for the treatment of
      B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to
      express chimeric antigen receptors (CARs) that target CD19 and contain human
      CD3zeta (CAR 63.z), composite CD28-CD3zeta or CD137-CD3zeta signaling domains
      (CARs 63.28.z and 63.137.z). RESULTS: Exposure of CD19-positive targets to CAR NK
      92 cells resulted in formation of conjugates between NK and cancer cells, NK-cell
      degranulation and selective cytotoxicity toward established B-cell leukemia and
      lymphoma cells. Likewise, the CAR NK cells displayed targeted cell killing of
      primary pre-B-ALL blasts that were resistant to parental NK-92. Although all
      three CAR NK-92 cell variants were functionally active, NK-92/63.137.z cells were
      less effective than NK-92/63.z and NK-92/63.28.z in cell killing and cytokine
      production, pointing to differential effects of the costimulatory CD28 and CD137
      domains. In a Raji B-cell lymphoma model in NOD-SCID IL2R gammanull mice,
      treatment with NK-92/63.z cells, but not parental NK-92 cells, inhibited disease
      progression, indicating that selective cytotoxicity was retained in vivo.
      CONCLUSIONS: Our data demonstrate that it is feasible to generate CAR-engineered
      NK-92 cells with potent and selective antitumor activity. These cells may become
      clinically useful as a continuously expandable off-the-shelf cell therapeutic
      agent.

PMID- 27887865
TI  - Overcoming the bottleneck of platelet lysate supply in large-scale clinical
      expansion of adipose-derived stem cells: A comparison of fresh versus three types
      of platelet lysates from outdated buffy coat-derived platelet concentrates.
AB  - BACKGROUND: Platelet lysates (PL) represent a promising replacement for xenogenic
      growth supplement for adipose-derived stem cell (ASC) expansions. However, fresh
      platelets from human blood donors are not clinically feasible for large-scale
      cell expansion based on their limited supply. Therefore, we tested PLs prepared
      via three methods from outdated buffy coat-derived platelet concentrates (PCs) to
      establish an efficient and feasible expansion of ASCs for clinical use. METHODS:
      PLs were prepared by the freeze-thaw method from freshly drawn platelets or from
      outdated buffy coat-derived PCs stored in the platelet additive solution,
      InterSol. Three types of PLs were prepared from outdated PCs with platelets
      suspended in either (1) InterSol (not manipulated), (2) InterSol + supplemented
      with plasma or (3) plasma alone (InterSol removed). Using these PLs, we compared
      ASC population doubling time, cell yield, differentiation potential and cell
      surface markers. Gene expression profiles were analyzed using microarray assays,
      and growth factor concentrations in the cell culture medium were measured using
      enzyme-linked immunosorbent assay (ELISA). RESULTS: Of the three PL compositions
      produced from outdated PCs, removal of Intersol and resuspension in plasma prior
      to the first freezing process was overall the best. This specific outdated PL
      induced ASC growth kinetics, surface markers, plastic adherence and
      differentiation potentials comparable with PL from fresh platelets. ASCs expanded
      in PL from fresh versus outdated PCs exhibited different expressions of 17
      overlapping genes, of which 10 were involved in cellular proliferation, although
      not significantly reflected by cell growth. Only minor differences in growth
      factor turnover were observed. CONCLUSION: PLs from outdated platelets may be an
      efficient and reliable source of human growth supplement allowing for large-scale
      ASC expansion for clinical use.

PMID- 27887864
TI  - Optimization of cGMP purification and expansion of umbilical cord blood-derived T
      regulatory cells in support of first-in-human clinical trials.
AB  - BACKGROUND AIMS: Thymic-derived regulatory T cells (tTreg) are critical
      regulators of the immune system. Adoptive tTreg transfer is a curative therapy
      for murine models of autoimmunity, graft rejection, and graft-versus-host disease
      (GVHD). We previously completed a "first-in-human" clinical trial using in vitro
      expanded umbilical cord blood (UCB)-derived tTreg to prevent GVHD in patients
      undergoing UCB hematopoietic stem cell transplantation (HSCT). tTreg were safe
      and demonstrated clinical efficacy, but low yield prevented further dose
      escalation. METHODS: To optimize yield, we investigated the use of KT64/86
      artificial antigen presenting cells (aAPCs) to expand tTreg and incorporated a
      single re-stimulation after day 12 in expansion culture. RESULTS: aAPCs increased
      UCB tTreg expansion greater than eightfold over CD3/28 stimulation. Re
      stimulation with aAPCs increased UCB tTreg expansion an additional 20- to 30
      fold. Re-stimulated human UCB tTreg ameliorated GVHD disease in a xenogeneic
      model. Following current Good Manufacturing Practice (cGMP) validation, a trial
      was conducted with tTreg. tTreg doses up to >30-fold higher compared with that
      obtained with anti-CD3/28 mAb coated-bead expansion and Foxp3 expression was
      stable during in vitro expansion and following transfer to patients. Increased
      expansion did not result in a senescent phenotype and GVHD was significantly
      reduced. DISCUSSION: Expansion culture with cGMP aAPCs and re-stimulation
      reproducibly generates sufficient numbers of UCB tTreg that exceeds the numbers
      of T effector cells in an UCB graft. The methodology supports future tTreg
      banking and is adaptable to tTreg expansion from HSC sources. Furthermore,
      because human leukocyte antigen matching is not required, allogeneic UCB tTreg
      may be a useful strategy for prevention of organ rejection and autoimmune
      disease.

PMID- 27887867
TI  - Evaluation of function and recovery of adipose-derived stem cells after exposure
      to paclitaxel.
AB  - BACKGROUND AIMS: Adipose-derived stem cells (ASCs) are considered to play a
      positive role in wound healing as evidenced by their increasing use in breast
      reconstructive procedures. After chemotherapy for breast cancer, poor soft tissue
      wound healing is a major problem. In the present study, the functional
      capabilities and recovery of ASCs after exposure to chemotherapeutic agent
      paclitaxel (PTX) using in vitro and ex vivo models were demonstrated. METHODS:
      Human ASCs were isolated from periumbilical fat tissue and treated with PTX at
      various concentrations. Adult Sprague-Dawley rats were given intravenous
      injections with PTX. Two and four weeks after the initial PTX treatment, ASCs
      were isolated from rat adipose tissue. Proliferation, cell viability, apoptosis
      and cell migration rates were measured by growth curves, MTT assays, flow
      cytometry and scratch assays. ASCs were cultured in derivative-specific
      differentiation media with or without PTX for 3 weeks. Adipogenic, osteogenic and
      endothelial differentiation levels were measured by quantitative reverse
      transcriptase polymerase chain reaction and histological staining. RESULTS: PTX
      induced apoptosis, decreased the proliferation and cell migration rates of ASCs
      and inhibited ASCs multipotent differentiation in both in vitro human ASC
      populations and ex vivo rat ASC populations with PTX treatment. Furthermore,
      after cessation of PTX, ASCs exhibited recovery potential of differentiation
      capacity in both in vitro and animal studies. CONCLUSIONS: Our results provide
      insight into poor soft tissue wound healing and promote further understanding of
      the potential capability of ASCs to serve as a cell source for fat grafting and
      reconstruction in cancer patients undergoing chemotherapy treatment.

PMID- 27887868
TI  - Reassessing APOBEC3G Inhibition by HIV-1 Vif-Derived Peptides.
AB  - The human APOBEC3G (A3G) enzyme restricts HIV-1 in the absence of the viral
      accessory protein viral infectivity factor (Vif) by deaminating viral cDNA
      cytosines to uracils. These uracil lesions base-pair with adenines during the
      completion of reverse transcription and result in A3G signature G-to-A mutations
      in the viral genome. Vif protects HIV-1 from A3G-mediated restriction by forming
      an E3-ubiquitin ligase complex to polyubiquitinate A3G and trigger its
      degradation. Prior studies indicated that Vif may also directly block the
      enzymatic activity of A3G and, provocatively, that Vif-derived peptides, Vif 25
      39 and Vif 105-119, are similarly inhibitory. Here, we show that Vif 25-39 does
      not inhibit A3G enzymatic activity and that the inhibitory effect of Vif 105-119
      and that of a shorter derivative Vif 107-115, although recapitulated, are non
      specific. We also elaborate a simple method for assaying DNA cytosine deaminase
      activity that eliminates potential polymerase chain reaction-induced biases. Our
      results show that these Vif-derived peptides are unlikely to be useful as tools
      to study A3G function or as leads for the development of future therapeutics.

PMID- 27887869
TI  - A Highly Diverse and Functional Naive Ubiquitin Variant Library for Generation of
      Intracellular Affinity Reagents.
AB  - We report the design, construction, and validation of a highly diverse phage
      displayed naive ubiquitin variant (Ubv) library. We first conducted a mutation
      tolerance scan of 27 residues and confirmed that 24 of these could be substituted
      by chemically diverse amino acids without compromising the display of Ubvs on
      phage. Subsequently, we constructed a library containing 6.8*1010 unique members,
      in which these 24 positions were diversified with a degenerate codon that encodes
      for 6 aa that are prevalent in protein interaction sites. To ensure the optimal
      structural stability of the Ubvs, we constructed the library in a two-step
      process, whereby 12 positions were randomized first, and following the selection
      for displayed Ubvs, the resulting pool was further diversified at the other 12
      positions. The resulting library was validated by conducting binding selections
      against a panel of 40 diverse protein antigens and was found to be as functional
      as a highly validated synthetic antibody library, yielding binders against 30 of
      the antigens. Detailed characterization of an Ubv that bound to the cell-surface
      receptor human epidermal growth factor receptor 3 revealed tight binding in the
      single-digit nanomolar range. Moreover, Ubvs that bound to two distinct sites on
      the intracellular adapter Grb2 could be combined to generate a potent inhibitor
      that functioned in cells. These results validate ubiquitin as a robust scaffold
      for the construction of naive libraries that can be used to generate Ubvs that
      target signaling networks both outside and inside the cells.

PMID- 27887870
TI  - Involvement of Indian hedgehog signaling in mesenchymal stem cell-augmented
      rotator cuff tendon repair in an athymic rat model.
AB  - BACKGROUND: Bone marrow aspirate has been used in recent years to augment tendon
      to-bone healing, including in rotator cuff repair. However, the healing mechanism
      in cell-based therapy has not been elucidated in detail. METHODS: Sixteen athymic
      nude rats were randomly allocated to 2 groups: experimental (human mesenchymal
      stem cells in fibrin glue carrier) and control (fibrin glue only). Animals were
      sacrificed at 2 and 4 weeks. Immunohistochemical staining was performed to
      evaluate Indian hedgehog (Ihh) signaling and SOX9 signaling in the healing
      enthesis. Macrophages were identified using CD68 and CD163 staining, and
      proliferating cells were identified using proliferating cell nuclear antigen
      staining. RESULTS: More organized and stronger staining for collagen II and a
      higher abundance of SOX9+ cells were observed at the enthesis in the experimental
      group at 2 weeks. There was significantly higher Gli1 and Patched1 expression in
      the experimental group at the enthesis at 2 weeks and higher numbers of Ihh+
      cells in the enthesis of the experimental group vs control at both 2 weeks and 4
      weeks postoperatively. There were more CD68+ cells localized to the tendon
      midsubstance at 2 weeks compared with 4 weeks, and there was a higher level of
      CD163 staining in the tendon midsubstance in the experimental group than in the
      control group at 4 weeks. CONCLUSION: Stem cell application had a positive effect
      on fibrocartilage formation at the healing rotator cuff repair site. Both SOX9
      and Ihh signaling appear to play an important role in the healing process.

PMID- 27887871
TI  - Radiographic results of augmented all-polyethylene glenoids in the presence of
      posterior glenoid bone loss during total shoulder arthroplasty.
AB  - BACKGROUND: Chronic osteoarthritis can result in glenohumeral subluxation and
      loss of posterior glenoid bone. This can alter normal glenohumeral biomechanics
      and affect the stress placed on the glenoid implant after total shoulder
      arthroplasty. This study evaluated the clinical and radiographic results of an
      augmented all-polyethylene glenoid for the treatment of glenoid osteoarthritis in
      the presence of posterior glenoid bone loss and determined whether any failures
      or complications occurred with short-term follow-up. METHODS: During a 2-year
      period, 21 patients were treated with an augmented glenoid for an index diagnosis
      of osteoarthritis with a biconcave glenoid and average posterior glenoid bone
      loss of 4.7 mm. Clinical outcomes were recorded for the American Shoulder and
      Elbow Surgeons Shoulder Assessment, Simple Shoulder Test, and active motion.
      Radiographic analysis included glenoid version, humeral head subluxation,
      component seating, ingrowth, and loosening. RESULTS: Significant improvements
      were demonstrated for American Shoulder and Elbow Surgeons Shoulder Assessment
      (52.3), Simple Shoulder Test (8.1), forward flexion (50 degrees ), external
      rotation (32 degrees ), and pain. Radiographic improvements were found for
      glenoid version (12 degrees ), humeral scapular alignment (23%), and humeral
      glenoid alignment (8%). Central peg ingrowth was demonstrated in all patients,
      and complete component seating was achieved in 19 patients. No complications were
      encountered, and no clinical or radiographic failures were identified.
      CONCLUSION: Augmented polyethylene glenoid components demonstrated improved
      clinical outcome, without implant failure or complications, during short-term
      follow-up.

PMID- 27887872
TI  - Optimizing the rehabilitation of elbow lateral collateral ligament injuries: a
      biomechanical study.
AB  - BACKGROUND: Elbow lateral collateral ligament (LCL) injury may arise after trauma
      or lateral surgical approaches. The optimal method of rehabilitating the LCL
      insufficient elbow is unclear. Therapists often prescribe active motion exercises
      with the forearm pronated. Recently, overhead exercises have become popular as
      they may enable gravity to compress the elbow joint, improving stability,
      although this has not been proved biomechanically. This investigation aimed to
      quantify the effects of several variables used in LCL injury rehabilitation on
      elbow stability. METHODS: Seven cadaveric specimens were tested in a custom elbow
      motion simulator in 3 arm positions (overhead, dependent, and varus) and 2
      forearm positions (pronation and supination) during passive and simulated active
      elbow extension. Three injury patterns were studied (intact, LCL injury, and LCL
      with common extensor origin injury). An electromagnetic tracking device measured
      ulnohumeral kinematics. RESULTS: Following combined LCL and common extensor
      origin injury, overhead positioning enhanced elbow stability relative to the
      other arm positions (P < .01 in pronation; P = .04 in supination). Active motion
      stabilized the LCL-deficient elbow in the dependent (P = .02) and varus (P < .01)
      positions. Pronation improved stability in the overhead (P = .05), dependent (P =
      .06), and varus (P < .01) positions. CONCLUSIONS: Rehabilitation with the arm
      overhead improves elbow stability after LCL injury. Initiating earlier range of
      motion in this "safe position" might decrease elbow stiffness and allow optimal
      ligament healing. If exercises are done in the dependent position, active motion
      with forearm pronation should be encouraged. Varus arm positioning should be
      avoided.

PMID- 27887873
TI  - Neer Award 2017: A rapid method for detecting Propionibacterium acnes in surgical
      biopsy specimens from the shoulder.
AB  - BACKGROUND: Propionibacterium (P) acnes infection of the shoulder after
      arthroplasty is a common and serious complication. Current detection methods for
      P acnes involve anaerobic cultures that require prolonged incubation periods
      (typically 7-14 days). We have developed a polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP) approach that sensitively and
      specifically identifies P acnes in tissue specimens within a 24-hour period.
      METHODS: Primers were designed to amplify a unique region of the 16S rRNA gene in
      P acnes that contained a unique HaeIII restriction enzyme site. PCR and RFLP
      analyses were optimized to detect P acnes DNA in in vitro cultures and in
      arthroscopic surgical biopsy specimens from patients with P acnes infections.
      RESULTS: A 564 base-pair PCR amplicon was derived from all of the known P acnes
      strains. HaeIII digests of the amplicon yielded a restriction fragment pattern
      that was unique to P acnes. P acnes-specific amplicons were detected in as few as
      10 bacterial cells and in clinical biopsy specimens of infected shoulder tissues.
      CONCLUSION: This PCR-RFLP assay combines the sensitivity of PCR with the
      specificity of RFLP mapping to identify P acnes in surgical isolates. The assay
      is robust and rapid, and a P acnes-positive tissue specimen can be confirmed
      within 24 hours of sampling, facilitating treatment decision making, targeted
      antibiotic therapy, and monitoring to minimize implant failure and revision
      surgery.

PMID- 27887874
TI  - Clinical and radiographic outcome of revision surgery of radial head prostheses:
      midterm results in 16 patients.
AB  - BACKGROUND: Little is known about revision surgery of radial head arthroplasty.
      The aim of this study was to report on the clinical and radiographic outcome of
      revision arthroplasty of the elbow with a bipolar metallic radial head
      prosthesis. METHODS: Between 2006 and 2013, we used either a press-fit or
      cemented RHS bipolar radial head prosthesis for revision surgery of radial head
      arthroplasty in 16 patients. Patients were prospectively enrolled in the study.
      Differences in outcome parameters before and after revision surgery were
      compared. RESULTS: At a mean follow-up of 75 months (range, 36-116 months), none
      of the revised radial head prostheses needed a second revision. None of the stems
      showed radiographic signs of loosening. In 1 patient the head was dissociated
      from the prosthesis. The average flexion-extension arc was 127 degrees  (range,
      105 degrees -140 degrees ), and the average pronation-supination arc was 138
      degrees  (range, 90 degrees -160 degrees ). Stability scores improved after
      revision surgery, resulting in 13 stable elbows (P = .01). In 8 patients the
      Oxford Elbow Score was between 37 and 48 points. The percentage of patients with
      either good or excellent results according to the Mayo Elbow Performance Score
      was 63%. The mean score on the EQ-5D (EuroQol Five Dimensions) was 80 (range, 63
      100), and the visual analog scale scores both for pain at rest and for pain with
      activity improved to 3 (range, 0-9) and 4 (range, 0-9), respectively (P < .001).
      All but 1 patient was satisfied with the results of the revision procedure.
      CONCLUSION: The clinical and radiographic outcomes of revision surgery of a
      radial head prostheses are favorable.

PMID- 27887875
TI  - Two-stage revision for infected shoulder arthroplasty.
AB  - BACKGROUND: Periprosthetic shoulder infections (PSIs) are challenging to treat
      and often result in significant patient morbidity. Without a standardized
      treatment protocol, PSIs are often managed similarly to periprosthetic hip and
      knee infections. Because 2-stage revision is the gold standard for treating
      periprosthetic hip and knee infections, we performed a case series and literature
      review to determine its effectiveness in PSIs. METHODS: We identified 19 patients
      (14 men) from our institution who were treated with a 2-stage revision after
      presenting with a PSI. Mean patient age was 63 +/- 9 years, and average body mass
      index was 30.8 +/- 5.8. The average time from the index arthroplasty to treatment
      was 40 months, 8 of 13 positive cultures were Propionibacterium acnes, and 9 of
      19 patients had multiple shoulder operations before presenting with infection.
      Minimum follow-up for all patients was 2 years. RESULTS: After a mean follow-up
      of 63 months (range, 25-184 months), 15 of 19 patients in our study were
      successfully treated for PSI. Average postoperative American Shoulder and Elbow
      Surgeons (ASES) Shoulder Assessment score was 69 (range, 32-98) and average
      postoperative forward elevation was significantly increased from 58 degrees  to
      119 degrees  (P < .001). The incidence of recurrent infection was 26%. The rate
      of noninfection complications was 16%, for a total complication rate of 42%.
      CONCLUSION: In patients with PSIs, especially those with intractable, chronic
      infections, a 2-stage revision represents a viable treatment option for
      eradicating infection and restoring function. However, it is important to
      recognize the risk of recurrent infection and postoperative complications in this
      challenging patient population.

PMID- 27887877
TI  - A discrete stage-structured model of California newt population dynamics during a
      period of drought.
AB  - We introduce a mathematical model for studying the population dynamics under
      drought of the California newt (Taricha torosa), a species of special concern in
      the state of California. Since 2012, California has experienced a record-setting
      drought, and multiple studies predict drought conditions currently underway will
      persist and even increase in severity. Recent declines and local extinctions of
      California newt populations in Santa Monica Mountain streams motivate our study
      of the impact of drought on newt population sizes. Although newts are terrestrial
      salamanders, they migrate to streams each spring to breed and lay eggs. Since egg
      and larval stages occur in water, a precipitation deficit due to drought
      conditions reduces the space for newt egg-laying and the necessary habitat for
      larval development. To mathematically forecast newt population dynamics, we
      develop a nonlinear system of discrete equations that includes demographic
      parameters such as survival rates for newt life stages and egg production, which
      depend on habitat availability and rainfall. We estimate these demographic
      parameters using 15 years of stream survey data collected from Cold Creek in Los
      Angeles County, California, and our model captures the observed decline of the
      parameterized Cold Creek newt population. Based upon data analysis, we predict
      how the number of available newt egg-laying sites varies with annual
      precipitation. Our model allows us to make predictions about how the length and
      severity of drought can affect the likelihood of persistence and the time to
      critical endangerment of a local newt population. We predict that sustained
      severe drought will critically endanger the newt population but that the newt
      population can rebound if a drought is sufficiently short.

PMID- 27887876
TI  - An accuracy study of computer-planned implant placement in the augmented maxilla
      using osteosynthesis screws.
AB  - Previous research on the accuracy of flapless implant placement of virtually
      planned implants in the augmented maxilla revealed unfavourable discrepancies
      between implant planning and placement. By using the osteosynthesis screws placed
      during the augmentation procedure, the surgical template could be optimally
      stabilized. The purpose of this study was to validate this method by evaluating
      its clinically relevant accuracy. Twelve consecutive fully edentulous patients
      with extreme resorption of the maxilla were treated with a bone augmentation
      procedure. Virtual implant planning was performed and a surgical template was
      manufactured. Subsequently, six implants were installed using the surgical
      template, which was only supported by the osteosynthesis screws. Implant
      deviations between planning and placement were calculated. A total of 72 implants
      were installed. Mean deviations found in the mesiodistal direction were 0.817mm
      at the implant tip and 0.528mm at the implant shoulder. The angular deviation was
      2.924 degrees . In the buccolingual direction, a deviation of 1.038mm was
      registered at the implant tip and 0.633mm at the implant shoulder. The angular
      deviation was 3.440 degrees . This study showed that implant placement in the
      augmented maxilla using a surgical template supported by osteosynthesis screws is
      accurate.

PMID- 27887879
TI  - Solitary osteochondroma arising in lumbar spinous process: Case report.
AB  - Solitary osteochondromas rarely occur in the axial skeleton. Those tumors mostly
      arise on the posterior elements of the cervical column causing various symptoms
      especially when developing within the spinal canal. Exophytic lumbar variety is
      uncommon presenting with palpable mass or spinal deformity. We report a 20-year
      old man presenting with a solid painless mass at the lower lumbar region.
      Radiological examinations revealed an exophytic lesion arising in the third
      lumbar spinous process appearing to be a solitary osteochondroma. The lesion was
      treated by en-bloc resection; histopathological examination confirmed the
      diagnosis of osteochondroma with no evidence of recurrence at the end of 2-year
      follow up.

PMID- 27887878
TI  - Poor pharmacological adherence to inhaled medicines compared with oral medicines
      in Japanese patients with asthma and chronic obstructive pulmonary disease.

PMID- 27887880
TI  - Anamnestic prediction of bucket handle compared to other tear patterns of the
      medial meniscus in stable knees.
AB  - OBJECTIVE: The aim of this study was to analyze and compare the preoperative
      anamnestic details between patients with an arthroscopic diagnosis of bucket
      handle and other tear patterns of the medial meniscus in stable knees. METHODS: A
      total of 204 patients (mean age 49.3 +/- 13 years) were included in the study.
      The mean age was 49.3 +/- 13 years. The study group included 65 patients (63
      males, 2 females) with an arthroscopic diagnosis of bucket handle tear and the
      control group included 139 patients (90 males, 49 females) with non-bucket handle
      tear patterns. The preoperative clinical assessments of the two groups were
      analyzed retrospectively. Anamnestic prediction for the diagnosis of a bucket
      handle tear was based upon various medical history parameters. Multivariate
      logistic regression was carried out to identify independent anamnestic factors
      for predicting isolated bucket handle tears of the medial meniscus compared to
      non-bucket handle tears. RESULTS: Analysis of the multivariate logistic
      regression yielded 3 statistically significant independent anamnestic risk
      factors for predicting isolated bucket handle tears of the medial meniscus: male
      gender (OR, 9.7; 95% CI, 1.1-37.6), locking events (OR, 4.6; 95% CI, 1.8-11.3)
      and pain in extension (OR, 6.9; 95% CI, 2.5-23.7). Other preoperative variables
      such as age, BMI, activity level, comorbidities, duration of symptoms, pain
      location, preceding injury and its mechanism had no significant effect on tear
      pattern. CONCLUSIONS: Preoperative strong clues for bucket handle tears of the
      medial meniscus in stable knees are male gender, locking events and limitation in
      extension. LEVEL OF EVIDENCE: Level III, Diagnostic study.

PMID- 27887881
TI  - Sedation versus no sedation: Are there differences in relatives' satisfaction
      with the Intensive Care Unit? A survey study based on data from a randomised
      controlled trial.
AB  - BACKGROUND: Currently there is a trend towards less or no use of sedation of
      mechanically ventilated patients. Still, little is known about how different
      sedation strategies affect relatives' satisfaction with the Intensive Care Unit
      (ICU). AIM: To explore if there was a difference in relatives' personal reactions
      and the degree of satisfaction with information, communication, surroundings,
      care and treatment in the ICU between relatives of patients who receive no
      sedation compared with relatives of patients receiving sedation during mechanical
      ventilation in the ICU. METHOD: A survey study using a questionnaire with 39
      questions was distributed to relatives of mechanically ventilated patients, who
      had been randomised to either sedation with daily wake up or no sedation.
      RESULTS: Forty-nine questionnaires were sent out and 36 relatives answered. The
      response rate was 73%. We found no differences in relatives' personal reactions
      or in the degree of satisfaction with information, communication, care and
      treatment in the ICU between relatives of patients in the two groups. Relatives
      of patients treated with no sedation felt more bothered by disturbances in the
      surroundings compared with relatives of patients who were sedated (p=0.03).
      CONCLUSION: Treating the patient during mechanical ventilation with no sedation
      does not affect relatives' satisfaction adversely.

PMID- 27887882
TI  - C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol
      Mannosides to Promote a Th1 Response during Infection.
AB  - Phosphatidyl-inositol mannosides (PIM) are glycolipids unique to mycobacteria and
      other related bacteria that stimulate host immune responses and are implicated in
      mycobacteria pathogenicity. Here, we found that the FcRgamma-coupled C-type
      lectin receptor DCAR (dendritic cell immunoactivating receptor; gene symbol
      Clec4b1) is a direct receptor for PIM. Mycobacteria activated reporter cells
      expressing DCAR, and delipidation of mycobacteria abolished this activity.
      Acylated PIMs purified from mycobacteria were identified as ligands for DCAR.
      DCAR was predominantly expressed in small peritoneal macrophages and monocyte
      derived inflammatory cells in lungs and spleen. These cells produced monocyte
      chemoattractant protein-1 (MCP-1) upon PIM treatment, and absence of DCAR or
      FcRgamma abrogated MCP-1 production. Upon mycobacterial infection, Clec4b1
      deficient mice showed reduced numbers of monocyte-derived inflammatory cells at
      the infection site, impaired IFNgamma production by T cells, and an increased
      bacterial load. Thus, DCAR is a critical receptor for PIM that functions to
      promote T cell responses against mycobacteria.

PMID- 27887884
TI  - Calcium phosphate nanoparticles functionalized with alendronate-conjugated
      polyethylene glycol (PEG) for the treatment of bone metastasis.
AB  - Because of the peculiarity of the bone microstructure, the uptake of
      chemotherapeutics often happens at non-targeted sites, which induces side
      effects. In order to solve this problem, we designed a bone-targeting drug
      delivery system that can release drug exclusively in the nidus of the bone.
      Alendronate (ALN), which has a high ability to target to hydroxyapatite, was used
      to fabricate double ALN-conjugated poly (ethylene glycol) 2000 material (ALN
      PEG2k-ALN). The ALN-PEG2k-ALN was characterized using 1H NMR and 31P NMR and
      FTIR. ALN-PEG2k-ALN-modified calcium phosphate nanoparticles (APA-CPNPs) with an
      ALN targeting moiety and hydrophilic poly (ethylene glycol) arms tiled on the
      surface was prepared for bone-targeted drug delivery. The distribution of ALN
      PEG2k-ALN was tested by X-ray photoelectron spectroscopy. Isothermal titration
      calorimetry data indicated that similar to free ALN, both ALN-PEG2k-ALN and APA
      CPNPs can bind to calcium ions. The bone-binding ability of APA-CPNPs was
      verified via ex vivo imaging of bone fragments. An in vitro release experiment
      demonstrated that APA-CPNPs can release drug faster in an acid environment than a
      neutral environment. Cell viability experiments indicated that blank APA-CPNPs
      possessed excellent biocompatibility with normal cells. Methotrexate (MTX) loaded
      APA-CPNPs have the same ability to inhibit cancer cells as free drug at high
      concentrations, while they are slightly weaker at low concentrations. All of
      these experiments verified the prospective application of APA-CPNPs as a bone
      targeting drug delivery system.

PMID- 27887883
TI  - Nanoprecipitated catestatin released from pharmacologically active microcarriers
      (PAMs) exerts pro-survival effects on MSC.
AB  - Catestatin (CST), a fragment of Chromogranin-A, exerts angiogenic, arteriogenic,
      vasculogenic and cardioprotective effects. CST is a very promising agent for
      revascularization purposes, in "NOOPTION" patients. However, peptides have a very
      short half-life after administration and must be conveniently protected.
      Fibronectin-coated pharmacologically active microcarriers (FN-PAM), are
      biodegradable and biocompatible polymeric microspheres that can convey
      mesenchymal stem cell (MSCs) and therapeutic proteins delivered in a prolonged
      manner. In this study, we first evaluated whether a small peptide such as CST
      could be nanoprecipitated and incorporated within FN-PAMs. Subsequently, whether
      CST may be released in a prolonged manner by functionalized FN-PAMs (FN-PAM-CST).
      Finally, we assessed the effect of CST released by FN-PAM-CST on the survival of
      MSCs under stress conditions of hypoxia-reoxygenation. An experimental design,
      modifying three key parameters (ionic strength, mixing and centrifugation time)
      of protein nanoprecipitation, was used to define the optimum condition for CST.
      An optimal nanoprecipitation yield of 76% was obtained allowing encapsulation of
      solid CST within FN-PAM-CST, which released CST in a prolonged manner. In vitro,
      MSCs adhered to FN-PAMs, and the controlled release of CST from FN-PAM-CST
      greatly limited hypoxic MSC-death and enhanced MSC-survival in post-hypoxic
      environment. These results suggest that FN-PAM-CST are promising tools for cell
      therapy.

PMID- 27887885
TI  - The watching-eyes phenomenon and blood donation: Does exposure to pictures of
      eyes increase blood donation by young adults?
AB  - This study examined the effectiveness of exposure to a "watching-eyes image" in
      increasing blood donation rates among young people, a segment of the population
      that is particularly underrepresented among blood donors. Participants were 454
      first-year university students, each of who was given a blood-donation flyer at
      the beginning of a lecture. Participants were randomly assigned to one of two
      conditions depending on whether the flyer they received bore a picture of eyes
      (experimental condition) or a neutral picture (control condition). We recorded
      the numbers of participants who promised to give blood and who actually gave
      blood during the blood drive. Results show that the number of people who gave
      blood was significantly higher in the experimental condition than in the control
      condition. These findings provide the first evidence of the effectiveness of the
      watching-eyes strategy in encouraging young people to give blood. We discuss the
      processes underlying the "watching-eyes effect" with respect to blood donation.

PMID- 27887886
TI  - Understanding the needs of older patients with narcolepsy.

PMID- 27887887
TI  - Late use of electronic media and its association with sleep, depression, and
      suicidality among Korean adolescents.
AB  - OBJECTIVE: The aim of this study was to investigate the association of
      adolescents' last electronic media use time with their sleep and mood
      disturbances, including depression and suicidality. We also examined whether
      sleep disturbances and duration mediated the relationship between last media use
      time and mood disturbances. METHODS: This cross-sectional, school-based, online
      survey was administered by the Sleep Center at Samsung Medical Center and the
      Korea Centers for Disease Control and Prevention (KCDC) in 2011. A total of
      26,395 participants (12,593 male and 13,802 female) were recruited from 150
      middle and high schools representative of nationwide adolescents from 15
      administrative districts in Korea. The sleep habits of participants on weekdays
      and weekends were evaluated using a questionnaire. Sleep disturbances,
      depression, and suicidality were assessed using the Korean versions of the Global
      Sleep Assessment Questionnaire, Epworth Sleepiness Scale, and Beck 19-item Scale
      for Suicide Ideation. We also collected last media use time, from which we
      subtracted actual bedtime. RESULTS: Late electronic media use was significantly
      associated with increased mood disturbances including depression and suicidality
      directly, but not indirectly via sleep duration or disturbances. CONCLUSION: Our
      results suggest that adolescents might benefit from the restricted use of
      electronic media after bedtime in terms of their mood and sleep. Moreover,
      education regarding media use at night might be helpful in preventing youth
      suicide.

PMID- 27887888
TI  - Evaluating outer segment length as a surrogate measure of peak foveal cone
      density.
AB  - Adaptive optics (AO) imaging tools enable direct visualization of the cone
      photoreceptor mosaic, which facilitates quantitative measurements such as cone
      density. However, in many individuals, low image quality or excessive eye
      movements precludes making such measures. As foveal cone specialization is
      associated with both increased density and outer segment (OS) elongation, we
      sought to examine whether OS length could be used as a surrogate measure of
      foveal cone density. The retinas of 43 subjects (23 normal and 20 albinism; aged
      6-67years) were examined. Peak foveal cone density was measured using confocal
      adaptive optics scanning light ophthalmoscopy (AOSLO), and OS length was measured
      using optical coherence tomography (OCT) and longitudinal reflectivity profile
      based approach. Peak cone density ranged from 29,200 to 214,000cones/mm2
      (111,700+/-46,300cones/mm2); OS length ranged from 26.3 to 54.5MUm (40.5+/
      7.7MUm). Density was significantly correlated with OS length in albinism
      (p<0.0001), but not normals (p=0.99). A cubic model of density as a function of
      OS length was created based on histology and optimized to fit the albinism data.
      The model includes triangular cone packing, a cylindrical OS with a fixed volume
      of 136.6MUm3, and a ratio of OS to inner segment width that increased linearly
      with increasing OS length (R2=0.72). Normal subjects showed no apparent
      relationship between cone density and OS length. In the absence of adequate AOSLO
      imagery, OS length may be used to estimate cone density in patients with
      albinism. Whether this relationship exists in other patient populations with
      foveal hypoplasia (e.g., premature birth, aniridia, isolated foveal hypoplasia)
      remains to be seen.

PMID- 27887889
TI  - Development of Intramammary Drug Delivery Systems: Novel In Vitro Release Method.
AB  - The aim of this study was to develop an in vitro release model for intramammary
      drug delivery system (IMDS) evaluation. This study was the first to establish an
      in vitro-in vivo correlation with investigation of an IMDS containing lasalocid.
      Three different methods including the standard United States Pharmacopeia
      dissolution method with apparatus 2, a modified United States Pharmacopeia method
      using a dialysis bag, or a specifically designed enhancer cell system, were
      assessed for the release study. Full cream milk and water were selected as the
      release media. In vivo evaluation was carried out by administering lasalocid IMDS
      into the udder of lactating Holstein dairy cows. Milk samples were collected and
      analyzed at selected time points after treatment. Dissolution data were fitted to
      various kinetic models. The results indicated that the release rate of lasalocid
      from IMDS was controlled by factors other than diffusion, which could include the
      sedimentation of lasalocid to the interface and the wetting of lasalocid
      particles by water at the interface of oil in the formulation and release media.
      The results obtained in vivo and in vitro were consistent. The in vitro
      assessment supports formulation design for early stage development and
      potentially for in vivo performance analysis.

PMID- 27887891
TI  - High Intake of Nonmilk Extrinsic Sugars Is Associated With Protein and
      Micronutrient Dilution in Home-Dwelling and Institutionalized Older People.
AB  - BACKGROUND: High dietary sugar intake may compromise protein and micronutrient
      intakes in people with low energy intakes. The results of micronutrient dilution
      studies in older people have been few and conflicting. We examined the
      nutritional status and nutrient intakes associated with nonmilk extrinsic sugars
      (NMES) intakes in older people representing a broad spectrum of both healthy and
      vulnerable older populations. DESIGN AND PARTICIPANTS: This cross-sectional study
      combined five Finnish data sets covering home-dwelling (n = 526) and
      institutionalized (n = 374) older people. Their nutritional status was assessed
      using Mini Nutritional Assessment (MNA) and nutrient intakes retrieved from 1- to
      3-day food records. The participants were divided into quartiles corresponding to
      the proportions of energy received from NMES. Energy, nutrient, and fiber intakes
      were classified according to the NMES quartiles, and the participants were
      divided according to their places of residence (home, institution). RESULTS: High
      NMES intakes were associated with older age, female sex, poor cognition, low MNA
      scores, immobility, and institutionalization. In all, 90% of the participants in
      the highest NMES quartile (Q4) were institutionalized. In the institutionalized
      individuals, low protein and micronutrient intakes were observed in both those
      with low energy intake (Q1) and in those with very high NMES intakes (Q4). In
      home-dwelling individuals, the nutrient intakes tended to decline linearly with
      increasing NMES intakes in protein and most micronutrients. CONCLUSIONS:
      Institutionalized older people consumed diets high in NMES, compared with those
      living at home, and their low energy and high NMES intakes were associated with
      low protein and micronutrient intakes.

PMID- 27887892
TI  - The Third Transition: The Clinical Evolution Oriented to the Contemporary Older
      Patient.

PMID- 27887890
TI  - Nonadditive Effects of Repetitive Administration of Lipoplexes in Immunocompetent
      Mice.
AB  - Repetitive administration is routinely used to maintain therapeutic drug levels,
      but previous studies have documented an accelerated blood clearance of some lipid
      based delivery systems under these conditions. To assess the effect of repetitive
      administration, non-PEGylated lipoplexes (+/-0.5) were administered 4 times via
      tail vein injection at 3-day intervals to immunocompetent BALB/c mice bearing 4T1
      tumors. This study measured the effect of repeat administration of nontargeted
      lipoplexes on clearance, cytokine/chemokine response, plasmid distribution,
      reporter gene expression, and liver toxicity. We do not observe a refractory
      period or a statistically significant difference in blood clearance between the
      first administration and subsequent injections of this lipoplex formulation,
      consistent with the absence of a cytokine/chemokine response. However, we do see
      a significant effect on both plasmid accumulation and expression, an enhancement
      of 26-fold and 10-fold in tumor plasmid levels and expression, respectively,
      after 4 injections as compared to that after a single injection. In addition, in
      vivo imaging suggests that expression in other organs had diminished rapidly 72 h
      after each administration, in contrast to relatively constant expression in the
      tumor. Taken together, the findings indicate that gene delivery to tumors can be
      dramatically enhanced by employing repetitive administration.

PMID- 27887893
TI  - Emotion modulation of the startle reflex in essential tremor: Blunted reactivity
      to unpleasant and pleasant pictures.
AB  - BACKGROUND: Essential tremor is a highly prevalent movement disorder
      characterized by kinetic tremor and mild cognitive-executive changes. These
      features are commonly attributed to abnormal cerebellar changes, resulting in
      disruption of cerebellar-thalamo-cortical networks. Less attention has been paid
      to alterations in basic emotion processing in essential tremor, despite known
      cerebellar-limbic interconnectivity. OBJECTIVES: In the current study, we tested
      the hypothesis that a psychophysiologic index of emotional reactivity, the
      emotion modulated startle reflex, would be muted in individuals with essential
      tremor relative to controls. METHODS: Participants included 19 essential tremor
      patients and 18 controls, who viewed standard sets of unpleasant, pleasant, and
      neutral pictures for six seconds each. During picture viewing, white noise bursts
      were binaurally presented to elicit startle eyeblinks measured over the
      orbicularis oculi. RESULTS: Consistent with past literature, controls' startle
      eyeblink responses were modulated according to picture valence (unpleasant >
      neutral > pleasant). In essential tremor participants, startle eyeblinks were not
      modulated by emotion. This modulation failure was not due to medication effects,
      nor was it due to abnormal appraisal of emotional picture content. CONCLUSIONS:
      Neuroanatomically, it remains unclear whether diminished startle modulation in
      essential tremor is secondary to aberrant cerebellar input to the amygdala, which
      is involved in priming the startle response in emotional contexts, or due to more
      direct disruption between the cerebellum and brainstem startle circuitry. If the
      former is correct, these findings may be the first to reveal dysregulation of
      emotional networks in essential tremor.

PMID- 27887894
TI  - Adult-onset pure tic disorder after post-traumatic hypoxic lesions of the globus
      pallidus.

PMID- 27887895
TI  - Clavicle fracture mimicking dropped-head syndrome in a patient with multiple
      system atrophy.

PMID- 27887896
TI  - Comorbid Parkinson's disease, falls and fractures in the 2010 National Emergency
      Department Sample.
AB  - INTRODUCTION: Parkinson's disease (PD) is a progressive, neurodegenerative
      disorder of multifactorial etiology affecting ~1% of older adults. Research
      focused on linking PD to falls and bone fractures has been limited in Emergency
      Department (ED) settings, where most injuries are identified. We assessed whether
      injured U.S. ED admissions with PD diagnoses were more likely to exhibit comorbid
      fall- or non-fall related bone fractures and whether a PD diagnosis with a
      concomitant fall or bone fracture is linked to worse prognosis. METHODS: We
      performed secondary analyses of 2010 Healthcare Utilization Project National ED
      Sample from 4,253,987 admissions to U.S. EDs linked to injured elderly patients.
      ED discharges with ICD-9-CM code (332.0) were identified as PD and those with ICD
      9-CM code (800.0-829.0) were used to define bone fracture location. Linear and
      logistic regression models were constructed to estimate slopes (B) and odds
      ratios (OR) with 95% confidence intervals (CI). RESULTS: PD admissions had 28%
      increased adjusted prevalence of bone fracture. Non-fall injuries showed stronger
      relationship between PD and bone fracture (ORadj = 1.33, 95% CI: 1.22-1.45) than
      fall injuries (ORadj = 1.06, 95% CI: 1.01-1.10). PD had the strongest impact on
      hospitalization length when bone fracture and fall co-occurred, and total charges
      were directly associated with PD only for fall injuries. Finally, PD status was
      not related to in-hospital death in this population. CONCLUSION: Among injured
      U.S. ED elderly patient visits, those with PD had higher bone fracture prevalence
      and more resource utilization especially among fall-related injuries. No
      association of PD with in-hospital death was noted.

PMID- 27887897
TI  - Nomenclature and diagnosis of gluten-related disorders: A position statement by
      the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO).
AB  - BACKGROUND: "Gluten-related disorders" is a term that encompasses different
      diseases induced by the ingestion of gluten-containing food. Because of their
      incidence the scientific community has been intensively studying them. AIM: To
      support gastroenterologists with a correct nomenclature and diagnostic approach
      to gluten-related disorders in adulthood. METHODS: The Italian Association of
      Hospital Gastroenterologists and Endoscopists (AIGO) commissioned a panel of
      experts to prepare a position statement clarifying the nomenclature and diagnosis
      of gluten-related disorders, focusing on those of gastroenterological interest.
      Each member was assigned a task and levels of evidence/recommendation have been
      proposed. RESULTS: The panel identified celiac disease, wheat allergy and non
      celiac gluten sensitivity as the gluten-related disorders of gastroenterological
      interest. Celiac disease has an autoimmune nature, wheat allergy is IgE-mediated
      while the pathogenesis of non-celiac gluten sensitivity is still unknown as is
      the case of non-IgE mediated allergy. Diagnosis should start with the serological
      screening for celiac disease and wheat allergy. In case of normal values, the
      response to a gluten-free diet should be evaluated and a confirmatory blind food
      challenge carried out. CONCLUSIONS: Gluten-related disorders are clinically
      heterogeneous. Patients should be carefully managed and specific protocols
      applied for a correct differential diagnosis in gastroenterological setting.

PMID- 27887898
TI  - In-Hospital Outcomes and Complications of Coronary Artery Bypass Grafting in the
      United States Between 2008 and 2012.
AB  - OBJECTIVE: To investigate the frequency and predictors of in-hospital
      complications among patients undergoing coronary artery bypass grafting (CABG) in
      the United States. DESIGN: Retrospective national database analysis SETTINGS:
      United States hospitals. PARTICIPANTS: A weighted sample of 1,910,236 patients
      undergoing CABG surgery identified from the National (Nationwide) Inpatient
      Sample from 2008 to 2012. INTERVENTIONS: CABG surgery MEASUREMENTS AND MAIN
      RESULTS: The number of CABG surgeries decreased from 436,275 in 2008 to 339,749
      in 2012. The Deyo comorbidity index showed a steady increase from 2008 to 2012.
      The rate of in-hospital mortality decreased from 2.7% in 2008 to 2.2% in 2012
      (p<0.001). The most common in-hospital complication was postoperative hemorrhage
      (30.4%), followed by cardiac (11.34%) and respiratory complications (2.3%).
      During the 5-year period, the rates of in-hospital cardiac, respiratory and
      infectious complications decreased (p<0.001), while the rate of postoperative
      hemorrhage showed a 35.8% relative increase in 2012 compared to 2008. CONCLUSION:
      The annual number of CABG surgeries is declining in the United States. While the
      burden of comorbidities is increasing, the rates of mortality and most in
      hospital complications are improving. The increasing rate of postoperative
      bleeding necessitates the need to develop strategies to improve the risk of
      bleeding in this patient population.

PMID- 27887899
TI  - Association of Preoperative Right and Left Ventricular Diastolic Dysfunction With
      Postoperative Atrial Fibrillation in Patients Undergoing Lung Surgery: A
      Prospective Observational Study.
AB  - OBJECTIVES: To clarify the relationship between right and left ventricular (RV
      and LV) diastolic function and postoperative atrial fibrillation (POAF). The
      early effects of major lung surgery on cardiac function in the intraoperative
      period during lung surgery were evaluated, using transesophageal
      echocardiography. DESIGN: Single-center prospective observational study. SETTING:
      A public hospital. PARTICIPANTS: Patients undergoing elective lobectomy with
      lymph node dissection for lung cancer (n = 116). INTERVENTIONS: Transesophageal
      echocardiography examination was performed under general anesthesia before skin
      incision (preoperative) and after chest closure (postoperative). According to
      measured echocardiographic variables, ventricular systolic and diastolic
      functions were classified at each time point. MEASUREMENTS AND MAIN RESULTS: Of
      the 116 patients, 24 (20.7%) experienced POAF. Preoperative RV and LV diastolic
      dysfunction were more common in patients with POAF than in those without POAF
      (58.3 v 28.3%, p = 0.008; 54.2 v 19.6%, p = 0.001, respectively). Among patients
      without preoperative diastolic dysfunction, a small number developed RV and LV
      diastolic dysfunction immediately after surgery (9.2% and 16.5%, respectively)
      and these distributions were comparable between patients with POAF and those
      without POAF. RV systolic dysfunction was observed in 6.5% of patients
      immediately after surgery and was not related to the occurrence of POAF.
      Multivariate analysis revealed older age, chronic obstructive pulmonary disease
      (COPD), and preoperative biventricular diastolic dysfunction as risk factors for
      POAF. CONCLUSIONS: Preoperative biventricular diastolic dysfunction, as well as
      older age and COPD, are associated with POAF in patients undergoing lobectomy.
      Major lung surgery has minimal early effects on postoperative systolic and
      diastolic functions.

PMID- 27887900
TI  - Pro: Antegrade/Retrograde Cerebral Perfusion Should Be Used During Major Aortic
      Surgery With Deep Hypothermic Circulatory Arrest.

PMID- 27887902
TI  - Pro: Pulmonary Artery Catheter Placement After Anesthetic Induction in Patients
      Undergoing Pulmonary Thromboendarterectomy.

PMID- 27887901
TI  - Procedural Management of Patients With Advanced Heart Failure Undergoing
      MitraClip Implantation (From the GRASP Registry).

PMID- 27887903
TI  - A Novel Approach to Assess the Three-Dimensional Anatomy of a Mitral Valve
      Regurgitant Jet Orifice.

PMID- 27887904
TI  - A new integrated symmetrical table for genetic codes.
AB  - Degeneracy is a salient feature of genetic codes, because there are more codons
      than amino acids. The conventional table for genetic codes suffers from an
      inability of illustrating a symmetrical nature among genetic base codes. In fact,
      because the conventional wisdom avoids the question, there is little agreement as
      to whether the symmetrical nature actually even exists. A better understanding of
      symmetry and an appreciation for its essential role in the genetic code formation
      can improve our understanding of nature's coding processes. Thus, it is worth
      formulating a new integrated symmetrical table for genetic codes, which is
      presented in this paper. It could be very useful to understand the Nobel laureate
      Crick's wobble hypothesis - how one transfer ribonucleic acid can recognize two
      or more synonymous codons, which is an unsolved fundamental question in
      biological science.

PMID- 27887905
TI  - A systematic review on the safety of Prostar XL versus ProGlide after TAVR and
      EVAR.
AB  - BACKGROUND: Endovascular aortic aneurysm repair (EVAR) and transfemoral
      transcatheter aortic valve replacement (TAVR) are widely spreading minimally
      invasive procedures performed mainly through the femoral artery. Prostar XL and
      ProGlide vascular closure devices are used in clinical practice for the
      hemostasis in these procedures and they have been shown to be safe and effective.
      PURPOSE: The aim of our systematic review is to compare the safety of these two
      devices for percutaneous closure of large arteriotomies in patients undergoing
      TAVR and EVAR. METHODS: We searched PubMed, EMBASE, Google Scholar and the
      Cochrane Central Register of Controlled Trials for all randomized and
      observational published studies that compared Prostar XL vs. ProGlide. Relative
      risk was calculated by random-effects model. Review Manager 5.1 was used for
      statistical analysis. RESULTS: A total number of 2909 patients were included in
      our analysis. The rate of overall vascular complications did not differ between
      Prostar XL and ProGlide {RR 1.35 (0.80-2.29), p=0.27}. In contrary, the risk
      ratio of all bleeding complications with Prostar XL compared to ProGlide was 1.82
      (1.47-2.24, p<0.001) and for major and life-threatening bleeding complications
      was 2.48 (1.65-3.73, p<0001, suggesting a lower bleeding risk with ProGlide). No
      statistical difference was found between groups for end-stage acute kidney injury
      (AKI), with a risk ratio of 2.14 (0.81-5.66), p=0.05. Finally, there were no
      differences in in-hospital and 30-days mortality rate between the two groups
      (1.41, 0.56-3.54, p=0.46 and 1.43, 0.55-3.73, p=0.47, respectively). CONCLUSIONS:
      Prostar XL is associated with greater risk of any bleeding as well as life
      threatening bleeding compared to the ProGlide device. However, no significant
      differences were observed in the rate of overall vascular complications, end
      stage AKI and in-hospital and 30-days mortality.

PMID- 27887907
TI  - Bodily illusions and weight-related disorders: Clinical insights from
      experimental research.

PMID- 27887906
TI  - Complex regional pain syndrome associated with hyperattention rather than neglect
      for the healthy side: A comprehensive case study.
AB  - Complex regional pain syndrome (CRPS) is a dehabilitating chronic condition
      occurring with peripheral lesions. There is growing consensus for a central
      contribution to CRPS. Although the nature of this central body representation
      disorder is increasingly debated, it has been repeatedly argued that CRPS results
      in motor neglect of the affected side. The present article describes a
      comprehensive and quantitative case report demonstrating that: (1) not all
      patients with chronic CRPS exhibit decreased spatial attention for the affected
      side and (2) patients may actually exhibit a substantial, broad and reliable
      attentional bias toward the painful side, akin to spatial neglect for the healthy
      side. This unexpected result agrees with the idea that patients can be hyper
      attentive toward their pathological side as a manifestation of lowered pain
      threshold, allodynia and kinesiophobia.

PMID- 27887908
TI  - The Yin and Yang of nucleic acid-based therapy in the brain.
AB  - The post-genomic era has unveiled the existence of a large repertory of non
      coding RNAs and repetitive elements that play a fundamental role in cellular
      homeostasis and dysfunction. These may represent unprecedented opportunities to
      modify gene expression at the right time in the correct space in vivo, providing
      an almost unlimited reservoir of new potential pharmacological agents. Hijacking
      their mode of actions, the druggable genome can be extended to regulatory RNAs
      and DNA elements in a scalable fashion. Here, we discuss the state-of-the-art of
      nucleic acid-based drugs to treat neurodegenerative diseases. Beneficial effects
      can be obtained by inhibiting (Yin) and increasing (Yang) gene expression,
      depending on the disease and the drug target. Together with the description of
      the current use of inhibitory RNAs (small inhibitory RNAs and antisense
      oligonucleotides) in animal models and clinical trials, we discuss the molecular
      basis and applications of new classes of activatory RNAs at transcriptional
      (RNAa) and translational (SINEUP) levels.

PMID- 27887909
TI  - Modified tubularized incised plate urethroplasty in distal hypospadias repair:
      Stepwise technique with validated functional and cosmetic outcome.
AB  - OBJECTIVE: To describe modification of the tubularized incised plate
      urethroplasty (TIP) for distal hypospadias, and assess its efficacy, and
      functional and cosmetic outcomes. METHODS: A prospective evaluation of a
      consecutive series of patients operated for primary distal hypospadias was
      conducted at a tertiary reference center. A standardized modification of the TIP
      (mTIP) procedure was performed on a 10 French catheter. Clinical data were
      collected in a dedicated database. Intraoperative variables, postoperative
      complications and outcomes, by means of uroflowmetries and a validated (HOPE)
      questionnaire, were assessed. Efficacy was evaluated with the reported
      complications: functional outcome was evaluated with uroflowmetries and cosmetic
      assessment by a validated questionnaire (HOPE). A descriptive statistical
      analysis was performed. RESULTS: Of the 112 boys operated between 30/09/2011 and
      1/04/2014, 50 completed long-term follow-up with functional and esthetic
      evaluation, as required for inclusion. Median age at surgery was 25 months (range
      14-156); median follow-up time was 21.5 months (range 6-48). Complications
      requiring re-intervention occurred in 2/50 boys. Uroflowmetry presented a bell
      shaped curve in 47/50 boys, and the median HOPE score was 9.5 (range 7.6-10.0).
      CONCLUSION: The mTIP procedure provided satisfactory long-term functional and
      cosmetic outcomes, as validated by uroflowmetries and standardized questionnaire.

PMID- 27887910
TI  - Assessment of serum level of corticotropin-releasing factor in primary nocturnal
      enuresis.
AB  - INTRODUCTION: Primary nocturnal enuresis is one of the sleep related phenomena
      characterized by disruption in the relationship between arousal and urination.
      Corticotropin-releasing factor (CRF) is a neurohormone released from the
      paraventricular nucleus of the hypothalamus into the median eminence to elicit
      release of adrenocorticotrophin from the anterior pituitary. It may act to
      modulate autonomic function and behavior in concert with the endocrine effects.
      Conflicting animal studies about the role of CRF in micturition, either
      facilitating or inhibiting, have been raised. It was suggested to be a novel
      target for treatment of urinary disorders based on the finding that manipulation
      of CRF in the pontine micturition circuit could affect urodynamic function. AIM:
      The aim was to throw light on the possible role of CRF in primary monosymptomatic
      nocturnal enuresis by assessing its serum level. SUBJECTS AND METHODS: Twenty
      nine children aged 8-14 years complaining of primary monosymptomatic nocturnal
      enuresis and 16 age- and sex-matched healthy children with good toilet control
      day and night were recruited to the study. History taking, clinical examination,
      and assessment of serum CRF levels in the morning and evening (9 a.m. and 9 p.m.)
      were carried out for all patients and controls. RESULTS AND DISCUSSION: A
      positive family history of enuresis was detected in 82.8% of enuretic patients.
      Serum levels of CRF (both morning and evening) were significantly lower in
      patients than in controls. Several animal studies suggested that CRF in
      descending projections from Barrington's nucleus to the lumbosacral
      parasympathetic neurons is inhibitory to micturition, which supports our results
      and the assumption that reduction of the evening serum CRF level could have a
      role in the occurrence of primary monosymptomatic nocturnal enuresis. No
      significant difference was found between morning and evening CRF serum levels in
      either cases or controls, which negates our assumption of having a rhythmic
      pattern of release (figure). No correlations with age were found. According to
      their history, all our enuretic patients were deep sleepers. Deep sleep and
      difficult arousal were found to have a major role in primary monosymptomatic
      nocturnal enuresis. It was proposed that CRF function may allow arousal to occur
      before micturition to facilitate preparative behaviors. A lower CRF level may
      explain deep-sleep pattern in children with enuresis. CONCLUSION: CRF was
      deficient in our enuretic children, which may draw attention to the possible
      pathophysiological implications in primary nocturnal enuresis (either at the
      level of loss of inhibitory effect on micturition or lack of arousal in response
      to bladder distension). Further proof studies are recommended.

PMID- 27887911
TI  - Does perception of catheterization limit its use in pediatric UTI?
AB  - INTRODUCTION: Urinary tract infections (UTIs) affect 3-8% of febrile children
      annually, but correctly diagnosing UTI in young children can present a challenge.
      Diagnosis requires a non-contaminated urine sample, which requires
      catheterization or suprapubic aspiration in infants and young children that have
      not completed toilet training. To improve adherence to these guidelines, it is
      critical to understand the barriers to urine testing and catheterization.
      OBJECTIVE: The purpose of this study was to investigate parental perception of
      pediatric UTI evaluation to better understand factors that impede urine testing
      prior to treatment of suspected UTI. STUDY DESIGN: We conducted an electronic,
      cross-sectional survey via social media targeting parents of children with a
      history of UTI. Participants were queried regarding demographics, urine specimen
      collection method, factors influencing urine collection method, and perception of
      the experience. Multivariable logistic regression was used to assess factors
      associated with catheterization distress and urine testing. RESULTS: Of 2726
      survey respondents, > 80% were female and White; 74% of the children with a
      history of UTI were female. Fifty-six percent of parents perceived extreme
      distress with catheterization. Among parents whose child was catheterized,
      extreme distress was less likely perceived if the parent was White (OR 0.6, 95%
      CI 0.4-0.9) or if the child was circumcised (OR 0.7, 95% CI 0.4-0.98). Among
      those whose child was not catheterized, extreme distress was more likely if
      parents had a college education (OR 3.2, 95% CI 2.2-4.5) and the child was more
      than 1 year old (OR 1.7, 95% CI 1.2-2.5). Catheterization was less likely to be
      withheld if parents had a college education (OR 0.1, 95% CI 0.1-0.2), and if the
      child was circumcised (OR 0.5, 95% CI 0.3-0.8) or had only one UTI (OR 0.6, 95%
      CI 0.4-0.8) (Table). DISCUSSION: Parental education level, child age, and
      circumcision status play an important role in the subjective distress associated
      with catheterization. This highlights the substantial impact of parental factors
      on adherence to guidelines for children suspected of UTI. For example, college
      educated parents were more likely to be offered catheterization. However, these
      parents are also more likely to associate the catheterization experience with
      extreme distress, possibly limiting their likelihood of consent to this
      procedure. More studies are required to better understand the impact of these
      factors on catheterization. But, it is clear that parental input has a
      substantial impact on the evaluation of their child's suspected UTI.

PMID- 27887912
TI  - Application of the STROBE statement to the hypospadias literature: Report of the
      international pediatric urology task force on hypospadias.
AB  - INTRODUCTION: Observational studies, particularly case series, represent the
      majority of the current hypospadias research. As a result, this literature lacks
      standardization of surgical techniques, uniform definitions of hypospadias
      complications, and consistency of outcome reporting, which may make it difficult
      to compare results across studies. A modified version of the STROBE statement,
      containing 20 items, was presented at the International Pediatric Urology Task
      Force on Hypospadias meeting to assist with clear and transparent reporting of
      hypospadias studies. The adoption and implementation of this modified tool will
      allow investigators and health care providers to critically evaluate quality and
      identify bias within the literature. In addition this instrument will ensure
      consistency of reporting, improving objective comparisons between studies,
      unification of results, and development of evidence-based clinical guidelines.
      METHODS: In this article, we have applied the modified STROBE statement to the
      hypospadias literature, aiming to create a guide on study reporting for pediatric
      urologists, and ultimately improve the quality of research in our field. We
      present itemized recommendations for adequate reporting of hypospadias studies
      and case series, ranging from drafting the abstract to addressing biases and
      potential sources of confounding. Included with each item is a brief explanation
      of its importance and potential effect on the study, as well as pertinent
      examples of hypospadias articles. RESULTS: A modified STROBE summary table
      containing 20 items is presented in (Supplementary Table 1). CONCLUSIONS: If
      properly conducted and reported, hypospadias studies have the potential to
      provide useful information to clinicians and surgeons. However, authors should
      recognize the inherent limitations of these observational studies, especially in
      the form of bias, which may introduce invalid data or limit generalizability.
      Thus, we expect that the use of this guiding tool will not only improve
      transparency of hypospadias reporting, but also improve its methodological
      quality, allowing proper comparison and interpretation of data across different
      institutions.

PMID- 27887914
TI  - Practical and functional classification of the double urethra: A variable,
      complex and fascinating malformation observed in 20 patients.
AB  - INTRODUCTION: Urethral duplication is a rare and variable malformation of the
      urinary tract, with non-univocal and complex management. In addition, different
      classification schemes have been proposed, but none have considered all the
      possible variants. OBJECTIVE: To report experience with the management of 20
      urethral duplication patients and propose a classification of this anomaly.
      MATERIALS AND METHODS: A retrospective analysis collecting information regarding
      20 patients (Table) with urethral duplication treated at a single institution
      over the past 40 years. Three females and 17 males were treated: two had vesico
      urethral duplication, eight had urethral duplication with a single bladder, and
      eight had 'lambda' duplication. RESULTS: Immediate postoperative complications
      included urethral dehiescence (n = 1) and urethral stenosis (n = 2). The
      progressive augmentation by dilating the urethra (PADUA) technique was
      ineffective. During follow-up, the following were recorded: urinary incontinence
      (n = 2), urinary tract infection (n = 3), hypertension (n = 3) and erectile
      dysfunction (n = 1). All patients were satisfied with the aesthetic result.
      DISCUSSION: Urethral duplication is a rare anomaly with male preponderance. Four
      types of duplication were described, on the basis of anatomy and management:
      vesical and urethral duplication (type 1), urethral duplication with single
      bladder (type 2), 'lambda-type' duplication (type 3) and 'miscellanea' (multiple
      urethral channels, spindle urethra, other female forms, type 4). A full
      description of the malformation and surgical approach was given for each type.
      The advantages of the classification were compared with the literature.
      CONCLUSIONS: The proposed classification should be a useful tool, based on the
      required surgical approach, even if surgery should be tailored to the patient. It
      is important to restore the anatomy and achieve urinary continence. Surgery can
      be challenging and a multi-step process, especially in cases of 'lambda'
      duplications.

PMID- 27887913
TI  - Prospective assessment of cosmesis before and after genital surgery.
AB  - INTRODUCTION: Little data exist about the surgical interventions taking place for
      children with disorders of sex development (DSD). Most studies that have
      evaluated cosmetic outcomes after genitoplasty have included retrospective
      ratings by a physician at a single center. OBJECTIVE: The present study aimed to:
      1) describe frequency of sex assignment, and types of surgery performed in a
      cohort of patients with moderate-to-severe genital ambiguity; and 2)
      prospectively determine cosmesis ratings by parents and surgeons before and after
      genital surgery. STUDY DESIGN: This prospective, observational study included
      children aged <2 years of age, with no prior genitoplasty at the time of
      enrollment, moderate-to-severe genital atypia, and being treated at one of 11
      children's hospitals in the United States of America (USA). Clinical information
      was collected, including type of surgery performed. Parents and the local
      pediatric urologist rated the cosmetic appearance of the child's genitalia prior
      to and 6 months after genitoplasty. RESULTS: Of the 37 children meeting
      eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY
      karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis
      overall was congenital adrenal hyperplasia (54%). Thirty-five children had
      surgery; 21 received feminizing genitoplasty, and 14 had masculinizing
      genitoplasty. Two families decided against surgery. At baseline, 22 mothers
      (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were
      dissatisfied or very dissatisfied with the appearance of the child's genitalia.
      Surgeons rated the appearance of the genitalia significantly worse than mothers
      (P < 0.001) and fathers (P <= 0.001) at baseline. At the 6-month postoperative
      visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all
      groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%)
      reported either a good outcome, or they were satisfied (see Summary Figure);
      there were no significant between-group differences in ratings. DISCUSSION: This
      multicenter, observational study showed surgical interventions being performed at
      DSD centers in the USA. While parent and surgeon ratings were discordant pre
      operatively, they were generally concordant postoperatively. Satisfaction with
      postoperative cosmesis does not necessarily equate with satisfaction with the
      functional outcome later in life. CONCLUSION: In this cohort of children with
      genital atypia, the majority had surgery. Parents and surgeons all rated the
      appearance of the genitalia unfavorably before surgery, with surgeons giving
      worse ratings than parents. Cosmesis ratings improved significantly after
      surgery, with no between-group differences.

PMID- 27887915
TI  - Voiding patterns of adult patients who underwent hypospadias repair in childhood.
AB  - OBJECTIVE: This study aimed at evaluating the voiding patterns of adult patients
      who underwent hypospadias repair in childhood. METHOD: Following IRB approval 103
      (22.7%) of 449 adult patients who underwent hypospadias repair between 1978 and
      1993 responded to the following questionnaires: International Prostate Symptom
      Score (I-PSS) and Short Form 12 questionnaire (SF-12). Uroflowmetry (UF) was
      performed for all patients. The patients were divided into three groups according
      to the primary meatus localization. Group I had 63 patients (61.5%) treated for
      glanular hypospadias, group II had 19 patients (18.4%) treated for distal
      hypospadias, and group III comprised the remaining 21 patients (20.4%) treated
      for proximal hypospadias. RESULTS: The mean +/- SD I-PSS score for all patients
      who responded to the questionnaire was 2.3 +/- 2.4, and UF was 21.1 +/- 4.3 mL/s.
      The patients from groups I and III had fewer urinary symptoms compared with those
      of the group II: 1.3 +/- 1.5, 5.5 +/- 2.4, and 1.6 +/- 1.4, respectively (p <
      0.0001). With regards to UF, the patients from the groups I and III did better
      compared with those from the group II: 22.1 +/- 4.1 mL/s, 18.91 +/- 4.2 mL/s, and
      20.11 +/- 3.42 mL/s, respectively (p = 0.021) (Figure). The UF was better in
      patients with normal vs. abnormal IPSS (p = 0.0064). The physical component
      summary was 49.8 +/- 10.3, 51.1 +/- 3.6, and 46.4 +/- 0.3 in groups I, II, and
      III, respectively. The mental summary component was 42.64 +/- 4.1, 42.2 +/- 2.4,
      and 39.89 +/- 2.9 in groups I, II, and III, respectively. CONCLUSIONS: Most of
      the adult patients who underwent hypospadias repair in childhood had normal or
      mild voiding disturbance, with no effects on their physical or mental status.

PMID- 27887916
TI  - Interfaces for noninvasive ventilation in the acute setting in children.
AB  - The use of noninvasive ventilation (NIV) is very specific in the acute setting as
      compared to its use in a chronic setting. In the Pediatric Intensive care Unit
      (PICU), NIV may be required around the clock and initiation has to be fast and
      easy. Despite the increasing use of non-invasive ventilation (NIV) and the larger
      choice of interfaces, data comparing the use of different interfaces for
      pediatric patients are scarce and recommendations for the most appropriate choice
      of interface are lacking. However, this choice in acute settings is crucial and a
      major contributor of the success of NIV. The aim of the present review was to
      describe the different types of interfaces available for children in the acute
      setting, their advantages and limitations, to highlight how to choose the optimal
      interface, and how to monitor the tolerance of the interface.

PMID- 27887917
TI  - MicroRNA-136 inhibits cancer stem cell activity and enhances the anti-tumor
      effect of paclitaxel against chemoresistant ovarian cancer cells by targeting
      Notch3.
AB  - To identify microRNAs (miRNAs) regulating Notch3 expression in association with
      paclitaxel resistance, candidate miRNAs targeting Notch3 were predicted using
      TargetScan. We found that miR-136 directly targets Notch3, and miR-136 was
      significantly downregulated in OSC tissues relative to normal control tissues,
      and low expression of miR-136 correlated with poor overall in ovarian cancer
      patients. Artificial miR-136 overexpression significantly reduced cell viability,
      proliferation, Cancer stem cell (CSC) spheroid formation, and angiogenesis, and
      increased apoptosis in paclitaxel-resistant SKpac cells compared with the effects
      of paclitaxel alone. miR-136 overexpression downregulated cell survival-
      (survivin, DNA-PK, pS6, S6) and cell cycle- (Cyclin D1, NF-kappaB) related
      proteins, and anti-apoptotic proteins (BCL2, and BCL-XL), and upregulated pro
      apoptotic proteins (Bim, Bid, and Bax). Taken together, miR-136 targets the
      Notch3 oncogene and functions as a tumor suppressor. miR-136 overexpression
      resensitized paclitaxel-resistant ovarian cancer cells and reduced CSC
      activities, suggesting a promising new target for the treatment of chemoresistant
      ovarian cancers.

PMID- 27887918
TI  - Giant Ilio-iliac Arteriovenous Fistula and Abdominal Aortic Aneurysm 32 Years
      after Penetrating Trauma.

PMID- 27887919
TI  - Homeostasis and the fuelling of metabolism: Comment on "Physics of metabolic
      organization" by Marko Jusup et al.

PMID- 27887920
TI  - Evaluation of body injury in organic personality disorder.

PMID- 27887921
TI  - Non-invasive prenatal diagnosis of thalassemias using maternal plasma cell free
      DNA.
AB  - Non-invasive prenatal testing (NIPT) using maternal plasma cell free DNA has
      already reshaped the existing prenatal care system for pregnancies screened for
      common chromosomal aneuploidies. On the other hand, much progress has been made
      in developing NIPT for monogenic diseases. Thalassemia served as a disease model
      to develop strategies for NIPT of monogenic traits. One approach focuses on the
      detection or exclusion of paternally inherited fetal mutations that are absent
      from the mother's genome. The assessment of maternally inherited mutations in
      maternal plasma requires the use of highly sensitive DNA quantification
      techniques. The relative mutation dosage (RMD) or the relative haplotype dosage
      (RHDO) approach provides a powerful tool to elucidate the fetal mutational status
      even in populations with lower genetic diversity, where the parents share the
      same mutation. With expected decrease in sequencing costs, NIPT for monogenic
      diseases is becoming an affordable option in prenatal care.

PMID- 27887923
TI  - The association between obesity and mental rotation ability in an adolescent
      sample.
AB  - Obesity has been related to deficient mental rotation performance. We assessed
      object-based and egocentric MR tasks in 19 obese and 19 normal-weight
      participants. Results showed slower response times of obese adolescents only for
      high angular disparities. This finding might emerge because of impairments in
      working memory, motor skills or perspective taking processes in obese youth.

PMID- 27887922
TI  - Obesity, foot pain and foot disorders in older men and women.
AB  - OBJECTIVE: We investigated obesity, foot pain and selected foot disorders, and
      determined if associations differed by foot posture or dynamic foot function.
      METHODS: We included 2445 men and women (4888 feet) from the Framingham Foot
      Study (2002-2008). A foot examination assessed presence of disorders and pain on
      each foot. Body mass index (BMI, kg/m2) was categorized as normal (<25),
      overweight (25-29.99), moderate-obesity (30-34.99) severe-obesity (35+). Foot
      posture (normal, cavus, planus) and dynamic foot function (normal, supinated,
      pronated) were defined using plantar pressure measurement system. We used sex
      specific logistic regression with generalized estimating equations to account for
      correlation between two feet of the same person, adjusted for age and stratified
      by foot posture and dynamic foot function. RESULTS: Average age was 68+/-11
      years, 56% female, average BMI 28+/-5kg/m2. 18% of feet had pain, 25% hallux
      valgus, 2% claw toes, 18% hammer toes, 7% overlapping toes. In men, severe
      obesity was associated with foot pain (OR=2.4, p=0.002) and claw toes (OR=3.4,
      p=0.04). In women, overweight, moderate-obesity and severe-obesity were
      associated with foot pain. Women with severe-obesity were less likely to have
      hallux valgus. Similar patterns were evident after stratification by foot posture
      and dynamic foot function. CONCLUSION: Both men and women were at increased odds
      of foot pain as BMI increased. Data suggested foot posture and dynamic foot
      function had no effect, thus are unlikely mechanisms.

PMID- 27887924
TI  - [A safe technique of Le Fort I osteotomy in bilateral cleft patients].
AB  - Le Fort I osteotomy is often needed in bilateral cleft patients. The usual
      approach to the maxillae may compromise the premaxillary vascularisation. We
      present a subperiosteal exposure preserving two paramedian vascular pedicles that
      respect premaxillary blood-supply.

PMID- 27887925
TI  - A large degenerated GI stromal tumor presenting as a peripancreatic cyst.

PMID- 27887926
TI  - Geographic Clustering of Acute Complications and Sociodemographic Factors in
      Adults with Type 1 Diabetes.
AB  - OBJECTIVES: To assess the geographic distribution of acute complications in
      patients with type 1 diabetes in a large urban centre; and to assess the
      association between acute complications and community-level sociodemographic
      factors. METHODS: Adults (aged >=18 years old) with type 1 diabetes and acute
      complications were identified between 2004 and 2008 by using a diabetes centre
      clinical database or discharge abstracts for acute complications (diabetic
      ketoacidosis or hypoglycemia). Using a geographic information system, hot-spot
      analysis was used to identify spatial clusters of acute complications in a large
      urban centre. The association between acute complications and community-level
      sociodemographic factors were assessed by Spearman rank correlation. RESULTS: We
      identified 1779 patients with type 1 diabetes, of whom 456 had been hospitalized
      for acute complications. The mean age of patients was 40.9+/-16.0 years, and men
      were more likely to have acute complications (59.2% vs. 52.3%; p<0.01). Spatial
      clusters of high values and low values were identified. Higher median family
      income (r=-0.36; p<0.0001) and higher education levels (r=-0.30; p<0.0001) were
      associated with lower rates of acute complications. CONCLUSIONS: This study
      demonstrated geographic clusters of hospitalizations for acute complications and
      important community sociodemographic factors. Prevention strategies and
      interventions targeting these geographic and sociodemographic disparities need to
      be explored as a means of minimizing hospitalizations for acute complications.

PMID- 27887927
TI  - Effects of in vitro, acute and chronic treatment with fluoxetine on the
      sympathetic neurotransmission of rat vas deferens.
AB  - It is described that fluoxetine treatment is able to induce ejaculatory
      disorders. However, the exact mechanism is still not fully understood. Therefore,
      this study was carried out to further evaluate the anti-ejaculatory effects of
      fluoxetine, using different approaches (in vitro or in vivo treatments), on the
      sympathetic neurotransmission of the rat vas deferens. Vas deferens from male
      Wistar rats were used to check the in vitro effects of fluoxetine 10-6M, 3.10-6M
      or 10-5M. Animals were also acutely (20mg/kg, i.p. 4h or 24h) or chronically
      (10mg/kg, i.p., 30days) treated with fluoxetine or drug-free vehicle. The vas
      deferens from non-treated and treated animals were isolated and mounted in an
      isolated organ bath for the study of the contractions induced by adrenergic
      agonists, tyramine, 5-HT, Ca2+ or electrical field stimulation. In vitro or acute
      treatment with fluoxetine decreased the contraction induced by agonists, Ca2+ or
      electrical field stimulation. The chronic treatment with fluoxetine decreased the
      contractions induced agonists, tyramine or Ca2+, but did not modify the
      contractions induced by electrical field stimulation. We have shown that in vitro
      or in vivo fluoxetine treatment is able to alter the sympathetic
      neurotransmission of the rat vas deferens which could be related to alterations
      in the calcium signalling.

PMID- 27887928
TI  - Degradation of paraoxon (VX chemical agent simulant) and bacteria by magnesium
      oxide depends on the crystalline structure of magnesium oxide.
AB  - In this work, our goal was to study the capability of a single metallic oxide to
      neutralize a chemical agent and to exhibit an antibacterial effect. We tested two
      types of magnesium oxides, MgO. The first MgO sample tested, which commercial
      data size characteristic was -325 mesh (MgO-1) destroyed in 3 h, 89.7% of
      paraoxon and 93.2% of 4-nitrophenol, the first degradation product. The second
      MgO sample, which commercial data size was <50 nm (MgO-2) neutralized in the same
      time, 19.5% of paraoxon and 10.9% of 4-nitrophenol. For MgO-1 no degradation
      products could be detected by GC-MS. MgO-1 had a bactericidal activity on
      Escherichia coli (6 log in 1 h), and showed a decrease of almost 3 log on a
      Staphylococcus aureus population in 3 h. MgO-2 caused a decrease of 2 log of a
      E.coli culture but had no activity against S. aureus. Neither of these two
      products had an activity on Bacillus subtilis spores. Analytical investigations
      showed that the real sizes of MgO nanoparticles were 11 nm for MgO-1 and 25 nm
      for MgO-2. Moreover, their crystalline structures were different. These results
      highlighted the importance of the size of the nanoparticles and their microscopic
      arrangements to detoxify chemical products and to inhibit or kill microbial
      strains.

PMID- 27887930
TI  - Paired editorial: Alcohol use risk in Adolescents 2 years after Bariatric
      Surgery.

PMID- 27887929
TI  - Anti-vascular inflammatory effects of pentacyclic triterpenoids from Astilbe
      rivularis in vitro and in vivo.
AB  - Sepsis is a systemic inflammatory condition resulting from bacterial infections.
      It is associated with high mortality rates, and its therapeutic options are
      limited. Transforming growth factor beta induced protein (TGFBIp) is an
      extracellular matrix protein that functions as a mediator of experimental sepsis.
      C-27-carboxylated pentacyclic triterpenoids are specifically found in species of
      the genus Astilbe, and show several biological effects. Given the anti
      inflammatory effects of pentacyclic triterpenoids, we investigated the effects of
      3beta-trans-p-coumaroyloxy-olean-12-en-27-oic acid (1) and 6beta-hydroxy-3
      oxoolean-12-en-27-oic acid (2) on TGFBIp-mediated vascular inflammatory
      responses. The anti-inflammatory activities of compounds 1 and 2 were determined
      by measuring the permeability, leukocyte adhesion and migration, and activation
      of pro-inflammatory proteins in TGFBIp-activated human umbilical vein endothelial
      cells (HUVECs) and mice. We found that compounds 1 and 2 inhibited
      lipopolysaccharide (LPS)-induced TGFBIp secretion, TGFBIp-induced barrier
      disruption, expression of cell adhesion molecules (CAMs), and the
      adhesion/transendothelial migration of the neutrophils to the human endothelial
      cells. Compounds 1 and 2 also suppressed TGFBIp-induced hyperpermeability and
      leukocyte migration in vivo. These results suggested that C-27-carboxylated
      pentacyclic triterpenoids 1 and 2 have anti-inflammatory functions by inhibiting
      hyperpermeability, CAM expression, and leukocyte adhesion/migration. Therefore,
      these compounds can be considered as a potential therapy for vascular
      inflammatory diseases.

PMID- 27887931
TI  - Revision of primary sleeve gastrectomy to Roux-en-Y gastric bypass: indications
      and outcomes from a high-volume center.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (SG) has become an accepted primary
      bariatric operation. Like other bariatric operations, inadequate weight loss and
      complications have been reported. OBJECTIVES: The aim of this study was to assess
      the indications and outcomes of revision of SG to laparoscopic Roux-en-Y gastric
      bypass (RYGB) at a single community hospital. SETTING: Community hospital, United
      States. METHODS: Retrospective review of a prospectively collected database
      identifying SG operations done from February 2009 to June 2014. All patients who
      underwent revision from SG to RYGB were studied. RESULTS: Forty-eight patients
      underwent revision of SG to RYGB. Mean time to revision was 26 months (range, 2
      60 mo) and mean follow up after RYGB was 20 months (range, 4-48 mo). Indications
      for revision were reflux (n = 14), inadequate weight loss (n = 11), reflux and
      inadequate weight loss (n = 16), stricture (n = 4), chronic leak (n = 1), and
      recurrent diabetes and reflux (n = 2). Reflux symptoms resolved in 96% of
      patients after revision, and hiatal hernias were repaired in 50% of patients.
      Percentage total weight loss at 3, 6, 12, 24, and 36 months was 9.0%, 12.9%,
      15.7%, 13.3%, and 6.5%, respectively. The overall rate of complication was 31%.
      There were no mortalities. CONCLUSIONS: Revision of SG to RYGB is a potentially
      effective means of treating SG complications, particularly reflux. Reflux was the
      most common indication for revision and was often associated with a hiatal
      hernia. Further studies will be necessary to evaluate the long-term maintenance
      of additional weight loss after revision of SG to RYGB.

PMID- 27887932
TI  - Assessing national provision of care: variability in bariatric clinical care
      pathways.
AB  - BACKGROUND: The American Society for Metabolic and Bariatric Surgery (ASMBS)
      Quality Improvement and Patient Safety (QIPS) Committee hypothesized that
      collecting and sharing clinical pathways could provide a valuable resource to new
      and existing bariatric programs. OBJECTIVE: To shed light on the variability in
      practice patterns across the country by analyzing pathways. SETTING: United
      States Centers of Excellence METHODS: From June 2014 to April 2015, clinical
      pathways pertaining to preoperative, intraoperative, and postoperative management
      of bariatric patients were solicited from the ASMBS executive council (EC), QIPS
      committee members, and state chapter presidents. Pathways were de-identified and
      then analyzed based on predetermined metrics pertaining to preoperative,
      intraoperative, and postoperative care. Concordance and discordance were then
      analyzed. RESULTS: In total, 31 pathways were collected; response rate was 80%
      from the EC, 77% from the QIPS committee, and 21% from state chapter presidents.
      The number of pathways sent in ranged from 1 to 10 with a median of 3 pathways
      per individual or institution. The majority of pathways centered on perioperative
      care (80%). Binary assessment (presence or absence) of variables found a high
      concordance (defined by greater than 65% of pathways accounting for that
      parameter) in only 6 variables: nutritional evaluation, psychological evaluation,
      intraoperative venous thromboembolism (VTE) prophylaxis, utilization of
      antiemetics in the postoperative period, a dedicated pain pathway, and
      postoperative laboratory evaluation. CONCLUSION: There is considerable national
      variation in clinical pathways among practicing bariatric surgeons. Most pathways
      center on Metabolic and Bariatric Surgery Accredited Quality Improvement Program
      (MBSAQIP) accreditation parameters, patient satisfaction, or Surgical Care
      Improvement Protocol (SCIP) measures. These pathways provide a path toward
      standardization of improved care.

PMID- 27887933
TI  - Prostate Artery Embolization for Benign Prostatic Hyperplasia: Current Status.
AB  - Prostate artery embolization has garnered much attention as a promising treatment
      for lower urinary tract symptoms secondary to benign prostatic hyperplasia. We
      aim to provide an up-to-date review of this minimally invasive technique,
      including discussion of potential benefits and technical challenges. Current
      evidence suggests it is a safe and effective option for patients with medication
      refractory urinary obstructive symptoms who are poor surgical candidates or
      refuse surgical therapy. Larger, randomized studies with long-term follow-up data
      are needed for this technique to be formally established in the treatment
      paradigm for benign prostatic hyperplasia.

PMID- 27887934
TI  - Currarino Syndrome in a Fetus, Infant, Child, and Adolescent: Spectrum of
      Clinical Presentations and Imaging Findings.
AB  - In 1981, Currarino et al described a triad of findings that consist of partial
      sacral dysgenesis, presacral mass (anterior meningocele, enteric cyst, or
      presacral teratoma) and anorectal malformation. Currarino syndrome exhibits
      variable expressivity and the clinical presentation tends to vary with the age of
      the subject such as spinal anomaly detected in the fetus, imperforate anus in the
      newborn, and intractable constipation or neurologic symptoms in the infant and
      older child. At any age, meningitis can be the presenting symptom and imaging is
      required for proper investigation. Meningitis, sepsis, urinary tract infections,
      and, rarely, malignant transformation of a teratoma are serious potential
      complications. This pictorial review describes the imaging findings, clinical
      history, surgical interventions, and genetic background in 5 children with this
      syndrome who presented in our hospital in the interval of 1 year.

PMID- 27887935
TI  - Prevalence of Extracranial Venous Narrowing on Magnetic Resonance Venography Is
      Similar in People With Multiple Sclerosis, Their Siblings, and Unrelated Healthy
      Controls: A Blinded, Case-Control Study.
AB  - PURPOSE: The study sought to assess and compare the prevalence of narrowing of
      the major extracranial veins in subjects with multiple sclerosis and controls,
      and to assess the sensitivity and specificity of magnetic resonance venography
      (MRV) for describing extracranial venous narrowing as it applies to the chronic
      cerebrospinal venous insufficiency theory, using catheter venography (CV) as the
      gold standard. METHODS: The jugular and azygos veins were assessed with time-of
      flight MRV in this assessor-blinded, case-control study of subjects with multiple
      sclerosis, their unaffected siblings, and unrelated controls. The veins were
      evaluated by diameter and area, and compared with CV. Collateral vessels were
      also analyzed for maximal diameter, as a potential indicator of compensatory
      flow. RESULTS: A high prevalence of extracranial venous narrowing was
      demonstrated in all study groups, collectively up to 84% by diameter criteria and
      90% by area, with no significant difference between the groups when assessed
      independently (P = .34 and .63, respectively). There was high interobserver
      variability in the reporting of vessel narrowing (kappa = 0.32), and poor vessel
      per vessel correlation between narrowing on MRV and CV (kappa = 0.064).
      Collateral neck veins demonstrated no convincing difference in maximum size or
      correlation with jugular narrowing. CONCLUSION: There is a high prevalence of
      narrowing of the major extracranial veins on MRV in all 3 study groups, with no
      significant difference between them. These findings do not support the chronic
      cerebrospinal venous insufficiency theory. Although MRV has shown a high
      sensitivity for identifying venous narrowing, time-of-flight imaging demonstrates
      poor interobserver agreement and poor specificity when compared with the gold
      standard CV.

PMID- 27887937
TI  - Intestinal Microbiome and Atherosclerosis.

PMID- 27887936
TI  - Prokineticin 2 Plays a Pivotal Role in Psoriasis.
AB  - Psoriasis is histologically characterized by keratinocytes (KC)
      hyperproliferation, inflammation, and increased angiogenesis, but the
      pathological factor responsible for these symptoms is unknown. Here, a
      neuroendocrine peptide (prokineticin 2, PK2), is highly expressed in human and
      mouse psoriatic skins but no significant change in other autoimmune diseases,
      suggesting that PK2 is a psoriasis-specific factor. Bacterial products
      significantly up-regulated PK2, implying that infection induces PK2 over
      expression. PK2 promoted KC and macrophage to produce interleukin-1 (IL-1), the
      central player of inflammation and psoriasis, which acts on adjacent fibroblast
      to induce inflammatory cascades and KC hyperproliferation. IL-1 feeds back on
      macrophages to induce PK2 production to perpetuate PK2-IL-1 positive feedback
      loop. PK2 also promoted angiogenesis, another psoriatic symptom. In mouse models,
      PK2 over-expression aggravated psoriasis while its knock-down inhibited
      pathological development. The results indicate that PK2 over-production
      perpetuates psoriatic symptoms by creating PK-2-IL-1 vicious loop. PK2 is a
      central player in psoriasis and a promising psoriasis-specific target.

PMID- 27887938
TI  - Molecular profiles in foregut oncology.
AB  - Oncology is and will continue to evolve resulting from a better understanding of
      the biology and intrinsic genetic profile of each cancer. Tumor biomarkers and
      targeted therapies are the new face of precision medicine, so it is essential for
      all physicians caring for cancer patients to understand and assist patients in
      understanding the role and importance of such markers and strategies to target
      them. This review was initiated in an attempt to identify, characterize, and
      discuss literature supporting clinically relevant molecular markers and
      interventions. The efficacy of targeting specific markers will be examined with
      data from clinical trials focusing on treatments for esophageal, gastric, liver,
      gallbladder, biliary tract, and pancreatic cancers.

PMID- 27887939
TI  - Re: Zhihua Lu, Guiting Lin, Amanda Reed-Maldonado, Chunxi Wang, Yung-Chin Lee,
      Tom F. Lue. Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile
      Function: A Systematic Review and Meta-analysis. Eur Urol 2017;71:223-33: Low
      intensity Extracorporeal Shock Wave Treatment of Erectile Dysfunction: Does the
      Shadow Exceed the Light?

PMID- 27887940
TI  - Re: A Narrative Review of Patient-reported Outcomes in Overactive Bladder: What
      is the Way of the Future?

PMID- 27887942
TI  - Progress in Prognosis and Prediction for Men with Prostate Cancer.

PMID- 27887941
TI  - Functional Outcomes and Quality of Life After Radical Prostatectomy Only Versus a
      Combination of Prostatectomy with Radiation and Hormonal Therapy.
AB  - BACKGROUND: While the optimal use and timing of secondary therapy after radical
      prostatectomy (RP) remain controversial, there are limited data on patient
      reported outcomes following multimodal therapy. OBJECTIVE: To assess the impact
      of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on
      urinary continence, potency, and quality of life (QoL) after RP. DESIGN, SETTING,
      AND PARTICIPANTS: Among 13150 men who underwent RP from 1992 to 2013, 905
      received RP + RT, 407 RP + ADT and 688 RP + RT + ADT. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSES: Urinary function, sexual function, and overall QoL were
      evaluated annually using self-administered validated questionnaires. Propensity
      score-matched and bootstrap analyses were performed, and the distributions for
      all functional outcomes were analyzed as a function of time after RP. RESULTS AND
      LIMITATIONS: Patients who received RP + RT had a 4% higher overall incontinence
      rate 3 yr after surgery, and 1% higher rate for severe incontinence (>3 pads/24h)
      compared to matched RP-only patients. ADT further increased the overall and
      severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT
      patients. RP + RT was associated with an 18% lower rate of potency compared to RP
      alone, while RP + RT + ADT was associated with a further 17% reduction compared
      to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12%
      compared to RP only and RP + RT, respectively. The timing of RT after RP had no
      influence on continence, but adjuvant compared to salvage RT was associated with
      significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%).
      Limitations of our study include the observational study design and potential for
      selection bias in the treatments received. CONCLUSIONS: Secondary RT and ADT
      after RP have an additive negative influence on urinary function, potency, and
      QoL. Patients with high-risk disease should be counseled before RP on the
      potential net impairment of functional outcomes due to multimodal treatment.
      PATIENT SUMMARY: Men with high-risk disease choosing surgery upfront should be
      counseled on the potential need for additional radiation and or androgen
      deprivation, and the potential net impairment of functional outcomes arising from
      multimodal treatment.

PMID- 27887943
TI  - Magnetic Resonance Imaging for Membranous Urethral Length Assessment Prior to
      Radical Prostatectomy: Can it Really Improve Prostate Cancer Management?

PMID- 27887944
TI  - Facing the Fate of the Remnant Urothelium After Radical Cystectomy: There Is Room
      for Improvement.

PMID- 27887945
TI  - Kisspeptin system in pejerrey fish (Odontesthes bonariensis). Characterization
      and gene expression pattern during early developmental stages.
AB  - In vertebrates, kisspeptins and their receptors are known to be related to
      puberty onset and gonadal maturation, however, there are few studies concerning
      their role in early development. Here, we characterize the kisspeptin system in
      the pejerrey, Odontesthes bonariensis, a fish with strong temperature-dependent
      sex determination. We reconstructed the phylogenetic history of the two ligands
      (kiss1 and kiss 2) and two receptors (kissr2 and kissr3) in pejerrey in the
      context of recent classifications of bony fishes, determined their tissue
      distribution and documented the early expression pattern of these ligands and
      receptors. Phylogenetic analysis of these gene families clearly resolved the
      percomorph clade and grouped pejerrey with Beloniformes. Paralogous sets of genes
      putatively arising from the teleost-specific genome duplication event (3R) were
      not detected. Kisspeptins and their receptors showed a wide tissue distribution
      in adult pejerrey, including tissues not related to reproduction. In larvae
      reared at 24 degrees C, the four kisspeptin elements were expressed in the head
      from week 1 to week 8 of life, with no differences in transcript levels. Larvae
      kept at a female-producing temperature (17 degrees C) did not show statistically
      significant differences in the transcript levels of all analyzed genes during the
      sex determination/differentiation period; however, in those larvae raised at male
      producing temperature (29 degrees C), kiss2 levels were increased at week 4 after
      hatching. These results showed that all members of the kisspeptin system are
      expressed at this early period, and the increase of kiss2 transcripts at week 4
      could be interpreted as it would be related to the differentiation of the brain
      pituitary axis in male development.

PMID- 27887946
TI  - Inhibition of eicosanoid signaling leads to increased lipid peroxidation in a
      host/parasitoid system.
AB  - We posed the hypothesis that inhibition of eicosanoid biosynthesis leads to
      increased lipid peroxidation in insects. Here we report that rearing the greater
      wax moth, Galleria mellonella, on media supplemented with selected inhibitors of
      eicosanoid biosynthesis throughout the larval, pupal and adult life led to major
      alterations in selected oxidative and antioxidative parameters of wax moth and
      its ectoparasitoid, Bracon hebetor. The highest dietary dexamethasone (Dex),
      esculetin (Esc) and phenidone (Phe) led to increased malondialdehyde (MDA) levels
      and to elevated catalase (CAT) and glutathione-S-transferase (GST) activities in
      all developmental stages of host larvae. Dietary Phe resulted in increased MDA
      levels, and CAT activity in G. mellonella adults by about 4-fold and about 2
      fold, respectively. The Phe effect on GST activity in all stages of the wax moth
      was expressed in a dose-dependent manner, increased to 140nmol/mg protein/min in
      larvae. MDA levels were increased by over 30-fold in adult wasps reared on Dex-
      and Esc-treated hosts. CAT and GST activities were increased in adult parasitoids
      reared on Esc-and Phe-treated hosts. GST activity of Dex-treated parasitoid
      larvae increased from about 4 to over 30nmol/mg protein/min. Dietary Phe led to
      increased GST activity, by about 25-fold, in adult wasps. These data indicate
      that chronic inhibition of eicosanoid biosynthesis leads to increased oxidative
      stress, strongly supporting our hypothesis. The significance of this work lies in
      understanding the roles of eicosanoids in insect biology. Aside from other well
      known eicosanoids actions, we propose that eicosanoids mediate reductions in
      oxidative stress.

PMID- 27887947
TI  - Berberine enhances the AMPK activation and autophagy and mitigates high glucose
      induced apoptosis of mouse podocytes.
AB  - High glucose concentration can induce injury of podocytes and berberine has a
      potent activity against diabetic nephropathy. However, whether and how berberine
      can inhibit high glucose-mediated injury of podocytes have not been clarified.
      This study tested the effect of berberine on high glucose-mediated apoptosis and
      the AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR)
      activation and autophagy in podocytes. The results indicated that berberine
      significantly mitigated high glucose-decreased cell viability, and nephrin and
      podocin expression as well as apoptosis in mouse podocytes. Berberine
      significantly increased the AMPK activation and mitigated high glucose and/or the
      AMPK inhibitor, compound C-mediated mTOR activation and apoptosis in podocytes.
      Berberine significantly enhanced the AMPK activation and protected from high
      glucose-induced apoptosis in the AMPK-silencing podocytes. Furthermore, berberine
      significantly increased the high glucose-elevated Unc-51-like autophagy
      activating kinase 1 (ULK1) S317/S555 phosphorylation, Beclin-1 expression, the
      ratios of LC3II to LC3I expression and the numbers of autophagosomes, but reduced
      ULK1 S757 phosphorylation in podocytes. In addition, berberine significantly
      attenuated compound C-mediated inhibition of autophagy in podocytes. The
      protective effect of berberine on high glucose-induced podocyte apoptosis was
      significantly mitigated by pre-treatment with 3-methyladenine or bafilomycin A1.
      Collectively, berberine enhanced autophagy and protected from high glucose
      induced injury in podocytes by promoting the AMPK activation. Our findings may
      provide new insights into the molecular mechanisms underlying the anti-diabetic
      nephropathy effect of berberine and may aid in design of new therapies for
      intervention of diabetic nephropathy.

PMID- 27887948
TI  - S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats
      via suppression of oxidative stress, inflammation, and acetylcholinesterase.
AB  - Diabetes mellitus (DM) is associated with learning, memory, and cognitive
      deficits. S-allyl cysteine (SAC) is the main organosulfur bioactive molecule in
      aged garlic extract with anti-diabetic, antioxidant, anti-inflammatory and
      nootropic property. This research was conducted to evaluate the efficacy of SAC
      on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic
      rats and to explore involvement of toll-like receptor 4 (TLR4), nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-kappa B (NF-kappaB), and heme
      oxygenase 1 (HO-1) signaling cascade. Male Wistar rats were divided into control,
      diabetic, SAC-treated diabetic, and glibenclamide-treated diabetic (positive
      control) groups. SAC was administered at a dose of 150mg/kg for seven weeks.
      Treatment of diabetic rats with SAC lowered serum glucose, improved spatial
      recognition memory in Y maze, discrimination ratio in novel object recognition
      task, and restored step-through latency (STL) in passive avoidance paradigm. In
      addition, SAC reduced acetylcholinesterase activity, lipid peroxidation marker
      malondialdehyde (MDA) and augmented antioxidant defensive system including
      superoxide dismutase (SOD), catalase and reduced glutathione (GSH) in hippocampal
      lysate. Meanwhile, SAC lowered hippocampal NF-kB, TLR4, and TNFalpha and
      prevented reduction of Nrf2 and heme oxygenase-1 (HO-1) in diabetic rats. Taken
      together, chronic SAC treatment could ameliorate cognitive deficits in STZ
      diabetic rats through modulation of Nrf2/NF-kappaB/TLR4/HO-1, and
      acetylcholinesterase and attenuation of associated oxidative stress and
      neuroinflammation.

PMID- 27887949
TI  - Pharmacological effects of a recombinant hPTH(1-34) derived peptide on
      ovariectomized rats.
AB  - A recombinant peptide Pro-Pro-[Arg11]hPTH(1-34)-Pro-Pro, was designed,
      biosynthesized, and purified in our lab (generated by substituting Arg for Leu at
      position 11 and adding -Pro-Pro to the carboxyl terminus of hPTH(1-34)-peptide),
      and reported to be capable of enhancing serum calcium level in chicken. In this
      investigation, we studied its impact on the structure, component, and
      biomechanical properties of rat bones. The pharmacological effect of Pro-Pro
      [Arg11]hPTH(1-34)-Pro-Pro was investigated to evaluate its therapeutic potential
      for the treatment of osteoporosis, one of the most prevalent and rapidly
      spreading diseases in the world. 3-month-old normal female rats were sham
      ovariectomized or ovariectomized, then fed for 14 weeks. Small doses of Pro-Pro
      [Arg11]hPTH(1-34)-Pro-Pro were given to the rats afterward (daily subcutaneous
      injection of 0.4-0.9nmol/100g body weight for 16 weeks). Values of various
      parameters, including the body weight, the bone mass, the bone geometry, the bone
      biomechanics, the bone histology, the bone histomorphology, and the serum
      biochemistry, were collected before or after animal sacrifice. Daily subcutaneous
      injection of Pro-Pro-[Arg11]hPTH(1-34)-Pro-Pro induced 37.0-42.4% increase in
      vertebral BMD, 28.5-47.9% increase in femoral BMD, 30.7-43.7% decrease in marrow
      cavity or increase in trabecular bone area. The peptide also increased calcium,
      phosphorus, and collagen in bone by 52.1-59.7%, 24.5-34.7%, and 26.3-28.0%,
      respectively. In terms of mechanic properties, peptide administration elevated
      bone rigidity by 55.7-84.5%, decreased the deflection by 14.8-26.7%, and improved
      modulus of elasticity by 28.1-76.4%. These data suggest Pro-Pro-[Arg11]hPTH(1-34)
      Pro-Pro has a positive effect on bone mass accumulation and microstructure
      improvement, fortifies bone strength, and possesses anti-aging capability, which
      may merit further investigation.

PMID- 27887950
TI  - CysLT2 receptor activation is involved in LTC4-induced lung air-trapping in
      guinea pigs.
AB  - CysLT1 receptors are known to be involved in the pathogenesis of asthma. However,
      the functional roles of CysLT2 receptors in this condition have not been
      determined. The purpose of this study is to develop an experimental model of
      CysLT2 receptor-mediated LTC4-induced lung air-trapping in guinea pigs and use
      this model to clarify the mechanism underlying response to such trapping. Because
      LTC4 is rapidly converted to LTD4 by gamma-glutamyltranspeptidase (gamma-GTP)
      under physiological conditions, S-hexyl GSH was used as a gamma-GTP inhibitor. In
      anesthetized artificially ventilated guinea pigs with no S-hexyl GSH treatment,
      i.v. LTC4-induced bronchoconstriction was almost completely inhibited by
      montelukast, a CysLT1 receptor antagonist, but not by BayCysLT2RA, a CysLT2
      receptor antagonist. The inhibitory effect of montelukast was diminished by
      treatment with S-hexyl GSH, whereas the effect of BayCysLT2RA was enhanced with
      increasing dose of S-hexyl GSH. Macroscopic and histological examination of lung
      tissue isolated from LTC4-/S-hexyl-GSH-treated guinea pigs revealed air-trapping
      expansion, particularly at the alveolar site. Inhaled LTC4 in conscious guinea
      pigs treated with S-hexyl GSH increased both airway resistance and airway
      hyperinflation. On the other hand, LTC4-induced air-trapping was only partially
      suppressed by treatment with the bronchodilator salmeterol. Although montelukast
      inhibition of LTC4-induced air-trapping was weak, treatment with BayCysLT2RA
      resulted in complete suppression of this air-trapping. Furthermore, BayCysLT2RA
      completely suppressed LTC4-induced airway vascular hyperpermeability. In
      conclusion, we found in this study that CysLT2 receptors mediate LTC4-induced
      bronchoconstriction and air-trapping in S-hexyl GSH-treated guinea pigs. It is
      therefore believed that CysLT2 receptors contribute to asthmatic response
      involving air-trapping.

PMID- 27887951
TI  - A Multi-Institutional Comparison of Clinicopathological Characteristics and
      Oncologic Outcomes of Upper Tract Urothelial Carcinoma in China and the United
      States.
AB  - PURPOSE: We evaluated differences in clinicopathological characteristics and
      oncologic outcomes between patients with upper tract urothelial carcinoma in
      mainland China and the United States. MATERIALS AND METHODS: We retrospectively
      compiled clinicopathological and oncologic outcomes data on patients with upper
      tract urothelial carcinoma treated surgically at tertiary care medical facilities
      in the United States or China from 1998 to 2015. Baseline demographics,
      comorbidities and pathological features were evaluated. Oncologic end points,
      including intravesical recurrence and cancer specific survival, were obtained
      after excluding patients who received systemic chemotherapy. Multivariable Cox
      regression was performed to determine predictors of adverse oncologic outcomes
      for each country. RESULTS: A total of 775 patients with upper tract urothelial
      carcinoma were identified, including 451 in China and 324 in the United States.
      Median followup was 42 months. American patients were more frequently male (65%
      vs 44%) and smokers (79% vs 18%), and had a worse mean ASA(r) (American Society
      of Anesthesiologists(r)) score (2.7 vs 2.2) and prior bladder cancer (41% vs 4%,
      all p <0.001). Chinese patients more often had preoperative hydronephrosis (56%
      vs 40%), high grade pathology (98% vs 77%), muscle invasion (64% vs 38%) and
      nodal metastases (26% vs 6%, all p <0.001). American patients had worse overall
      survival on Kaplan-Meier analysis (p = 0.049). However, country of origin did not
      predict local relapse or cancer specific survival. CONCLUSIONS: Patient and
      disease characteristics of upper tract urothelial carcinoma differed between the
      Chinese and American cohorts. Chinese patients appeared relatively healthier at
      presentation but more often exhibited adverse pathological features. While
      evaluation and management patterns may account for these variations, the
      pathological findings may reflect a differential underlying pathogenesis of
      disease. Additional study is warranted to further characterize these differences.

PMID- 27887952
TI  - Mini review: Update on bioaugmentation in anaerobic processes for biogas
      production.
AB  - Anaerobic digestion (AD) is increasingly being used and exploited as a strategy
      to generate biomethane, which can be used as a renewable and clean energy. AD
      rests on the biodegradation of organic compounds in anaerobic condition, and
      these organic compounds are generally agricultural-, industrial- and domestic
      wastes. However, problems of AD decrease efficiency, as the result of bioreactor
      stress, are generally encountered. The primarily cause of this stress is the
      presence of high concentrations of inhibitory substances such as nitrate,
      sulfate, heavy metals and oxygen among others. Another cause of AD decrease
      efficiency is the use of organic compounds that are less amenable to
      biodegradation such as lignocellulosic compounds. One of the strategies to
      overcome these limitations is the addition in bioreactors of "stress resistant"-
      or "efficient biomethane generating"- microorganisms to improve AD process. This
      strategy, known as bioaugmentation, has been used for the last 15 years to
      increase biomethane production. In this review, work carried out on this
      bioaugmentation process has been summarised, and new strategies that could be
      used or exploited to improve the success of this approach have also been
      discussed.

PMID- 27887953
TI  - Reply to Meisel et al.

PMID- 27887954
TI  - The Short-Chain Fatty Acid Sodium Butyrate Functions as a Regulator of the Skin
      Immune System.
AB  - There is evidence that gut commensal microbes affect the mucosal immune system
      via expansion of regulatory T cells (Tregs) in the colon. This is mediated via
      short-chain fatty acids, bacterial metabolites generated during fiber
      fermentation, which include butyrate, propionate, and acetate. We postulated that
      short-chain fatty acids produced by commensal skin bacteria may also activate
      resident skin Tregs, the activity of which is diminished in certain inflammatory
      dermatoses. Sodium butyrate (SB) either injected subcutaneously or applied
      topically onto the ears of hapten-sensitized mice significantly reduced the
      contact hypersensitivity reaction. This effect was histone acetylation-dependent
      because suppression was abrogated by anacardic acid, a histone acetyltransferase
      inhibitor. The genes encoding for the Treg-specific transcription factor foxp3
      and for IL-10 were up-regulated upon treatment with sodium butyrate, as
      determined by quantitative real-time reverse transcription-PCR.
      Immunofluorescence analysis showed enhanced numbers of Foxp3-positive cells in
      sodium butyrate-treated skin. Additionally, CD4+CD25- nonregulatory human T cells
      exerted suppressive features upon incubation with sodium butyrate. This indicates
      that Tregs can be induced by short-chain fatty acids, suggesting (i) that
      resident skin microbes may prevent exaggerated inflammatory responses by exerting
      a down-regulatory function and thereby maintaining a stable state under
      physiologic conditions and (ii) that short-chain fatty acids may be used
      therapeutically to mitigate inflammatory skin reactions.

PMID- 27887955
TI  - Treatment of Hypereosinophilic Syndrome with Cutaneous Involvement with the JAK
      Inhibitors Tofacitinib and Ruxolitinib.

PMID- 27887956
TI  - [Childhood's ophthalmologic involvement in Sturge-Weber-Krabbe syndrome].
AB  - Ophthalmologic involvement in Sturge-Weber-Krabbe syndrome (SWKS) is present in
      30-70% of cases and needs to be reviewed because of its impact on visual
      development. We report a case of a newborn for whom SSWK with ophthalmologic
      involvement was suspected. She had a right segmental plane angioma associated
      with right congenital glaucoma and suspected right pial angioma. Ophthalmic
      involvement in SWKS may be nonocular: iatrogenic by treatment-associated
      complications and central by leptomeningeal damage. Ophthalmologic involvement
      can occur throughout childhood and is mainly represented by glaucoma and diffuse
      choroidal hemangioma and then conjunctival hemangioma, retinal detachment, and
      iris heterochromia. SWKS requires multidisciplinary care with eye examination and
      prolonged follow-up as soon as clinical suspicion arises.

PMID- 27887957
TI  - Moving toward mechanical control of cardiac arrest.

PMID- 27887958
TI  - On the article "Findings questioning the involvement of Sigma-1 receptor in the
      uptake of anisamide-decorated particles" [J. Control. Release 224 (2016) 229
      238]: Letter to the Editor 1 (September 14, 2016).

PMID- 27887959
TI  - Decreased plasma concentrations of brain-derived neurotrophic factor in
      preeclampsia.
AB  - BACKGROUND: Preeclampsia (PE) is a disease characterized by excessive maternal
      inflammatory response. Early studies suggested that brain-derived neurotrophic
      factor (BDNF) modulates inflammation. The main objective of this study was to
      investigate BDNF plasma concentrations in PE women and to compare with BDNF
      concentrations from normotensive pregnant women. We also investigated the
      association among the plasma concentrations of BDNF and inflammatory mediators,
      and maternal clinical features. METHODS: BDNF plasma concentrations were measured
      by ELISA in 38 PE women (17 early onset and 21 late onset) and in 20 normotensive
      pregnant women (Norm) matched for gestational age (Norm<34weeks: n=8;
      Norm>=34weeks: n=12). Correlation analyses between laboratory parameters and
      clinical characteristics were evaluated through Spearman's coefficients. RESULTS:
      BDNF concentration was lower in PE women than in normotensive pregnant women, but
      no difference was detected between the subgroups of PE women and normotensive
      pregnant women. BDNF correlated negatively with annexin A1, and positively with
      body mass index and diastolic blood pressure. No correlation was significant in
      normotensive pregnant women. CONCLUSIONS: Lower BDNF plasma concentrations and
      cross-talk between BDNF and AnxA1 signaling pathways might be involved in PE
      pathogenesis.

PMID- 27887960
TI  - Corticosteroid-binding globulin cleavage may be pathogen-dependent in bloodstream
      infection.
AB  - OBJECTIVE: The process of enzymatic cleavage of high- to low-affinity
      corticosteroid-binding globulin (haCBG to laCBG) by neutrophil elastase leads to
      local tissue release of cortisol. Recently Pseudomonas aeruginosa was shown to
      instigate CBG cleavage with release of free cortisol in vitro. Hence, CBG
      cleavage with release of anti-inflammatory cortisol in infection may be pathogen
      dependent. Our objective was to determine whether haCBG and laCBG levels are
      altered in infected patients compared with controls, and whether these
      alterations were particular to causative bacteria. DESIGN: An observational,
      cross-sectional study at a public pathology institution and tertiary hospital in
      Adelaide, South Australia. METHODS: 100 positive blood culture samples and 100
      healthy control samples were analysed for serum total CBG, haCBG, laCBG, total
      and free cortisol, leukocyte and neutrophil count, C-reactive protein and Pitt
      severity score. RESULTS: Patients with infection had lower serum total CBG, haCBG
      and laCBG, all P<0.0001, than healthy controls. This was true in patients with
      and without a systemic inflammatory response and in those with culture-positive
      and culture-negative infections. Pseudomonas aeruginosa infection was associated
      with the lowest total and laCBG levels of the pathogen groups despite having the
      lowest inflammatory markers. CONCLUSIONS: There was evidence of CBG cleavage in
      early infection both in patients with and without systemic inflammation and
      regardless of culture status. Pseudomonas infection appeared to enhance cleavage.
      This observation, along with cleavage in severe neutropenia suggests mechanisms
      other than neutrophil elastase may be involved in CBG cleavage and local tissue
      cortisol release in infection.

PMID- 27887961
TI  - Clinical perspective: creating an effective practice peer review process-a
      primer.
AB  - Peer review serves as an important adjunct to other hospital quality and safety
      programs. Despite its importance, the available literature contains virtually no
      guidance regarding the structure and function of effective peer review
      committees. This Clinical Perspective provides a summary of the purposes,
      structure, and functioning of effective peer review committees. We also discuss
      important legal considerations that are a necessary component of such processes.
      This discussion includes useful templates for case selection and review. Proper
      committee structure, membership, work flow, and leadership as well as close
      cooperation with the hospital medical executive committee and legal
      representatives are essential to any effective peer review process. A thoughtful,
      fair, systematic, and organized approach to creating a peer review process will
      lead to confidence in the committee by providers, hospital leadership, and
      patients. If properly constructed, such committees may also assist in monitoring
      and enforcing compliance with departmental protocols, thus reducing harm and
      promoting high-quality practice.

PMID- 27887962
TI  - Synthesis of a biological active beta-hairpin peptide by addition of two
      structural motifs.
AB  - The idea of privileged scaffolds - that there seem to be more bioactive compounds
      found around some structures than others - is well established for small drug
      molecules, but has little significance for standalone peptide secondary
      structures whose adaptable shapes escape the definition of a 3D motif in the
      absence of a protein scaffold. Here, we joined two independent biological
      functions in a single highly restricted peptide to support the hypothesis that
      the beta-hairpin shape is the common basis of two otherwise unrelated biological
      recognition processes. To achieve this, the hydrophobic cluster HWX4LV from the
      decapeptide cyclic hairpin model peptide C1-C10cyclo-CHWEGNKLVC was included in
      the bicyclic peptide 2. The designed beta-hairpin peptide C4-C17, C8-C13bicyclo
      KHQCHWECTZGRCRLVCGRSGS (2, Z=citrulline), serves, on the one hand, as a specific
      epitope for rheumatoid autoantibodies and, on the other hand, shows a not
      negligible antibiotic effect against the bacterial strain E. coli AS19.

PMID- 27887963
TI  - Animal models in the pharmacokinetic/pharmacodynamic evaluation of antimicrobial
      agents.
AB  - Animal infection models in the pharmacokinetic/pharmacodynamic (PK/PD) evaluation
      of antimicrobial therapy serve an important role in preclinical assessments of
      new antibiotics, dosing optimization for those that are clinically approved, and
      setting or confirming susceptibility breakpoints. The goal of animal model
      studies is to mimic the infectious diseases seen in humans to allow for robust
      PK/PD studies to find the optimal drug exposures that lead to therapeutic
      success. The PK/PD index and target drug exposures obtained in validated animal
      infection models are critical components in optimizing dosing regimen design in
      order to maximize efficacy while minimize the cost and duration of clinical
      trials. This review outlines the key components in animal infection models which
      have been used extensively in antibiotic discovery and development including
      PK/PD analyses.

PMID- 27887964
TI  - Anti-inflammatory tetraquinane diterpenoids from a Crinipellis species.
AB  - The small pro-inflammatory 10kDa chemokine CXCL10 (Interferon-inducible protein
      10, IP-10) plays an important role in mediating immune responses through the
      activation and recruitment of leukocytes such as T cells, eosinophils, monocytes
      and NK cells to the sites of inflammation. Elevated levels of CXCL10 have been
      associated with chronic inflammatory and infectious diseases and therefore CXCL10
      represents an attractive target for the development of new anti-inflammatory
      drugs. In a search for anti-inflammatory compounds from fungi inhibiting the
      inducible CXCL10 promoter activity, four new tetraquinane diterpenoids,
      crinipellin E (1), crinipellin F (2), crinipellin G (3) and crinipellin H (4)
      were isolated from fermentations of a Crinipellis species. The structures of the
      compounds were elucidated by a combination of one- and two-dimensional NMR
      spectroscopy and mass spectrometry. Compounds 1, 2, and 3 inhibited the LPS/IFN
      gamma induced CXCL10 promoter activity in transiently transfected human MonoMac6
      cells in a dose-dependent manner with IC50 values of 15MUM, 1.5MUM, and 3.15MUM
      respectively, whereas compound 4 was devoid of any biological activity. Moreover,
      compounds 1, 2 and 3 reduced mRNA levels and synthesis of pro-inflammatory
      mediators such as cytokines and chemokines in LPS/IFN-gamma stimulated MonoMac6
      cells.

PMID- 27887965
TI  - Muropeptide signature of inhibitors of protein synthesis correlates with beta
      lactam synergism against methicillin-resistant Staphylococcus aureus.
AB  - Quinupristin/dalfopristin (Q/D) and beta-lactams interact positively against
      methicillin-resistant Staphylococcus aureus (MRSA). The effect extends to other
      inhibitors of protein synthesis, but not to inhibitors of polynucleotide
      synthesis or assembly, or to Q/D plus non-beta-lactam cell wall inhibitors.
      Moreover, electron microscopy studies have correlated this effect with a
      thickened cell wall. In this study, we sought to determine whether inhibitors of
      protein synthesis might produce a specific peptidoglycan muropeptide signature
      that would correlate with their positive beta-lactam interaction. The
      muropeptides of six S. aureus isolates (three methicillin-susceptible and three
      MRSA) were analysed using high-performance liquid chromatography and mass
      spectrometry. Exposure to 0.25* the minimum inhibitory concentration of
      inhibitors of protein synthesis consistently produced three main alterations
      irrespective of methicillin resistance: (i) an increase in peak 12 (a cyclic
      dimer of glycine-containing disaccharide-tetrapeptide); (ii) an increase in
      poorly resolved late-eluting materials; and (iii) a decrease in peak 1 (a
      disaccharide-pentapeptide). Eventually, the rate of autolysis was also decreased,
      supporting the structural alteration of the peptidoglycan. Other drug classes did
      not produce these anomalies. An increase in peak 12 was also observed in
      staphylococci treated with fosfomycin, which decreases expression of the native
      penicillin-binding protein (PBP) 2 and 4. Parallel blockage of normal PBPs with
      beta-lactams abolished the anomalies, indicating that they resulted from altered
      function of native PBPs. This underlines the potential of inhibiting both protein
      synthesis and transpeptidation simultaneously and suggests that such a drug
      combination strategy might be efficaciously exploited.

PMID- 27887966
TI  - Forgotten antibiotics: a follow-up inventory study in Europe, the USA, Canada and
      Australia.
AB  - The objective of this study was to update a 2011 survey, conducted on behalf of
      the ESCMID Study Group for Antibiotic Policies (ESGAP), studying the availability
      of old but clinically useful antibiotics in North America, Europe and Australia.
      This follow-up survey was performed in 2015 in 40 countries among specialists
      from the pharmaceutical, infectious diseases and microbiology sectors in North
      America, Europe and Australia in order to assess the availability through usual
      marketing processes of 36 systemic antibiotics (addition of 3 antibiotics
      compared with the 2011 survey) selected for their ability to treat infections
      caused by resistant bacteria and their unique value for specific criteria. The
      questionnaire was sent by e-mail to national contacts belonging to ESGAP and
      ReAct networks. In all, 39 of the 40 countries participated in this survey. The
      number of available antibiotics differed considerably from one drug to another as
      well as from one country to another (e.g. 7 antibiotics available in Estonia, 24
      in France). Overall, 25/36 selected antibiotics were marketed in 20/39 countries
      or less. From 2011 to 2015 (data available for both periods in 37 countries for
      33 antibiotics), the number of available selected antibiotics increased in 13
      countries and decreased in 17. In conclusion, despite the ongoing bacterial
      resistance crisis, the situation regarding the availability of 'forgotten
      antibiotics' has worsened since 2011. Urgent measures are needed to ensure better
      availability of these antibiotics on a global scale as a conservation measure to
      ensure sustainable and responsible use of antibiotics.

PMID- 27887968
TI  - Enteral Access Procedures: An 18-Year Analysis of Changing Patterns of
      Utilization in the Medicare Population.
AB  - PURPOSE: To evaluate national trends in enteral access and maintenance procedures
      for Medicare beneficiaries with regard to utilization rates, specialty group
      roles, and sites of service. MATERIALS AND METHODS: Using Medicare Physician
      Supplier Procedure Summary Master Files for the period 1994-2012, claims for
      gastrostomy and gastrojejunostomy access and maintenance procedures were
      identified. Longitudinal utilization rates were calculated using annual
      enrollment data. Procedure volumes by site of service and medical specialty were
      analyzed. RESULTS: Between 1994 and 2012, de novo enteral access procedure
      utilization decreased from 61.6 to 42.3 per 10,000 Medicare Part B beneficiaries
      (-31%). Gastroenterologists and surgeons performed > 80% of procedures (unchanged
      over study period) with 97% in the hospital setting. Over time, relative use of
      an endoscopic approach (62% in 1994; 82% in 2012) increased as percutaneous (21%
      to 12%) and open surgical (17% to 5%) procedures declined. Existing enteral
      access maintenance services increased 29% (from 20.1 to 25.9 per 10,000
      beneficiaries). Radiologists (from 13% to 31%) surpassed gastroenterologists
      (from 36% to 21%) as dominant providers of maintenance procedures. Emergency
      physicians (from 8% to 23%) and nonphysician providers (from 0% to 6%) have seen
      rapid growth as maintenance services providers as these services have
      transitioned increasingly to the emergency department setting (from 18% to 32%).
      CONCLUSIONS: Among Medicare beneficiaries, de novo enteral access procedures have
      declined in the last 2 decades as existing access maintenance services have
      increased. The latter are increasingly performed by radiologists, emergency
      physicians, and nonphysician providers.

PMID- 27887967
TI  - Percutaneous Image-Guided Cryoablation for the Treatment of Phantom Limb Pain in
      Amputees: A Pilot Study.
AB  - PURPOSE: To prospectively evaluate percutaneous image-guided nerve cryoablation
      for treatment of refractory phantom limb pain (PLP) in a pilot cohort for
      purposes of deriving parameters to design a larger, randomized, parallel-armed,
      controlled trial. MATERIALS AND METHODS: From January 2015 to January 2016, 21
      patients with refractory PLP underwent image-guided percutaneous cryoneurolysis
      procedures. Visual analog scale scores were documented at baseline and 7, 45, and
      180 days after the procedure. Responses to a modified Roland Morris Disability
      Questionnaire were documented at baseline and 7 and 45 days after the procedure.
      RESULTS: Technical success rate of the procedures was 100%. There were 6 (29%)
      minor procedure-related complications. Disability scores decreased from a
      baseline mean of 11.3 to 3.3 at 45-day follow-up (95% confidence interval 5.8,
      10.3; P < .0001). Pain intensity scores decreased from a baseline mean of 6.2 to
      2.0 at long-term follow-up (95% confidence interval 2.8, 5.6; P < .0001).
      CONCLUSIONS: Image-guided percutaneous nerve cryoablation is feasible and safe
      and may represent a new efficacious therapeutic option for patients with phantom
      pains related to limb loss.

PMID- 27887971
TI  - Biosorption of U(VI) by modified Hottentot Fern: Kinetics and equilibrium
      studies.
AB  - Batch experiments were conducted to investigate the biosorption of U(VI) onto
      Hottentot Fern (Cyclosorus interruptus). The selective adsorption, the adsorption
      of different sections of Cyclosorus interruptus (CI), and the adsorption of
      polluted CI compared with that of unpolluted one were studied in detail. The raw
      CI and the CI modified by CaCl2, MgCl2, MgCl2/H2O2 were investigated for
      adsorption of U(VI) from aqueous solution. The results indicate that raw CI
      showed good adsorption selectivity for U(VI), compared with the adsorption of
      Cu(II), Co(II) and Ni(II). The stem of CI possesses a prominent adsorption
      capacity compared to the leaf and root of CI, and the unpolluted CI showed its
      superiority in adsorption capacity than the polluted CI. Adsorption rate was very
      fast during the first 30 min in the whole adsorption process. The pseudo-second
      order kinetics model was proposed for the adsorption of U(VI) and the equilibrium
      data fitted well to Langmuir adsorption isotherms. The maximum adsorption
      capacity of R-CI, Ca-CI, Mg-CI and Mg/H2O2-CI is 41.67, 52.63, 62.50 and 71.43 mg
      g-1 at 20  degrees C, respectively.

PMID- 27887970
TI  - Production and release rate of 37Ar from the UT TRIGA Mark-II research reactor.
AB  - Air samples were taken at various locations around The University of Texas at
      Austin's TRIGA Mark II research reactor and analyzed to determine the
      concentrations of 37Ar, 41Ar, and 133Xe present. The measured ratio of 37Ar/41Ar
      and historical records of 41Ar releases were then utilized to estimate an annual
      average release rate of 37Ar from the reactor facility. Using the calculated
      release rate, atmospheric transport modeling was performed in order to determine
      the potential impact of research reactor operations on nearby treaty verification
      activities. Results suggest that small research reactors (~1 MWt) do not release
      37Ar in concentrations measurable by currently proposed OSI detection equipment.

PMID- 27887969
TI  - Flexible head-casts for high spatial precision MEG.
AB  - BACKGROUND: In combination with magnetoencephalographic (MEG) data, accurate
      knowledge of the brain's structure and location provide a principled way of
      reconstructing neural activity with high temporal resolution. However, measuring
      the brain's location is compromised by head movement during scanning, and by
      fiducial-based co-registration with magnetic resonance imaging (MRI) data. The
      uncertainty from these two factors introduces errors into the forward model and
      limit the spatial resolution of the data. NEW METHOD: We present a method for
      stabilizing and reliably repositioning the head during scanning, and for co
      registering MRI and MEG data with low error. RESULTS: Using this new flexible and
      comfortable subject-specific head-cast prototype, we find within-session
      movements of <0.25mm and between-session repositioning errors around 1mm.
      COMPARISON WITH EXISTING METHOD(S): This method is an improvement over existing
      methods for stabilizing the head or correcting for location shifts on- or off
      line, which still introduce approximately 5mm of uncertainty at best (Adjamian et
      al., 2004; Stolk et al., 2013; Whalen et al., 2008). Further, the head-cast
      design presented here is more comfortable, safer, and easier to use than the
      earlier 3D printed prototype, and give slightly lower co-registration errors
      (Troebinger et al., 2014b). CONCLUSIONS: We provide an empirical example of how
      these head-casts impact on source level reproducibility. Employment of the
      individual flexible head-casts for MEG recordings provide a reliable method of
      safely stabilizing the head during MEG recordings, and for co-registering MRI
      anatomical images to MEG functional data.

PMID- 27887972
TI  - Radon as a natural tracer for underwater cave exploration.
AB  - The Molnar Janos cave is one of the largest hypogenic caves of the Buda Thermal
      Karst (Budapest, Hungary) and mainly characterized by water-filled passages. The
      major outflow point of the waters of the cave system is the Boltiv spring, which
      feeds the artificial Malom Lake. Previous radon measurements in the cave system
      and in the spring established the highest radon concentration (71 BqL-1) in the
      springwater. According to previous studies, the origin of radon was identified as
      iron-hydroxide containing biofilms, which form where there is mixing of cold and
      thermal waters, and these biofilms efficiently adsorb radium from the thermal
      water component. Since mixing of waters is responsible for the formation of the
      cave as well, these iron-hydroxide containing biofilms and the consequent high
      radon concentrations mark the active cave forming zones. Based on previous radon
      measurements, it is supposed that the active mixing and cave forming zone has to
      be close to the spring, since the highest radon concentration was measured there.
      Therefore radon mapping was carried out with the help of divers in order to get a
      spatial distribution of radon in the cave passages closest to the spring. Based
      on our measurements, the highest radon activity concentration (84 BqL-1) was
      found in the springwater. Based on the distribution of radon activity
      concentrations, direct connection was established between the spring and the
      Istvan-room of the cave, which was verified by an artificial tracer. However, the
      distribution of radon in the cave passages shows lower concentrations (18-46 BqL
      1) compared to the spring, therefore an additional deep inflow from hitherto
      unknown cave passages is assumed, from which waters with high radon content
      arrive to the spring. These passages are assumed to be in the active cave
      formation zone. This study proved that radon activity concentration distribution
      is a useful tool in underwater cave exploration.

PMID- 27887973
TI  - Decommissioning strategy for liquid low-level radioactive waste surface storage
      water reservoir.
AB  - The Techa Cascade of water reservoirs (TCR) is one of the most environmentally
      challenging facilities resulted from FSUE "PA "Mayak" operations. Its reservoirs
      hold over 360 mln m3 of liquid radioactive waste with a total activity of some 5
      * 1015 Bq. A set of actions implemented under a special State program involving
      the development of a strategic plan aimed at complete elimination of TCR
      challenges (Strategic Master-Plan for the Techa Cascade of water reservoirs)
      resulted in considerable reduction of potential hazards associated with this
      facility. The paper summarizes the key elements of this master-plan: defining TCR
      final state, feasibility study of the main strategies aimed at its attainment,
      evaluation of relevant long-term decommissioning strategy, development of
      computational tools enabling the long-term forecast of TCR behavior depending on
      various engineering solutions and different weather conditions.

PMID- 27887975
TI  - Human exposure to brominated flame retardants through the consumption of fish and
      shellfish in Tarragona County (Catalonia, Spain).
AB  - The concentrations of 19 brominated flame retardants (BFRs) (8 polybrominated
      diphenyl ethers (PBDEs), 8 methoxylated PBDEs (MeO-PBDEs) and 3 emerging flame
      retardants) were determined in 10 species of fish and shellfish widely consumed
      in Tarragona County (Catalonia, Spain), by pressurized liquid extraction followed
      by gas chromatography coupled to tandem mass spectrometry. A higher occurrence of
      PBDEs was found in all the analyzed samples, while MeO-PBDEs were only detected
      in a few ones and the levels of emerging pollutants were relatively low. In
      contrast, hexabromobenzene was found in almost all samples at concentrations
      ranging between non detected and 0.2 ng g-1 wet weight (w.w.). Salmon, sole,
      hake, cod and tuna showed the highest concentrations of SigmaPBDEs (>0.8 ng g-1
      w.w.), while mussel was the species with the highest level of MeO-PBDEs (1.5 ng g
      1 w.w.). The dietary exposure of BFRs through consumption of these 10 species of
      fish and shellfish by the population of Tarragona County was estimated for
      different subpopulations, classified according to age and gender. Furthermore,
      calculations were performed in upper-, middle- and lower-bound risk scenarios.
      According to our data, the current concentrations of BFRs in fish and shellfish
      suggest no significant health risks for the consumers.

PMID- 27887976
TI  - The establishment of a telestroke service using multimodal CT imaging decision
      assistance: "Turning on the fog lights".
AB  - Telestroke services have been shown to increase stroke therapy access in rural
      areas. The implementation of advanced CT imaging for patient assessment may
      improve patient selection and detection of stroke mimics in conjunction with
      telestroke. We implemented a telestroke service supported by multimodal CT
      imaging in a rural hospital in Australia. Over 21months we conducted an
      evaluation of service activation, thrombolysis rates and use of multimodal
      imaging to assess the feasibility of the service. Rates of symptomatic
      intracranial haemorrhage and 90-day modified Rankin Score were used as safety
      outcomes. Fifty-eight patients were assessed using telestroke, of which 41 were
      regarded to be acute ischemic strokes and 17 to be stroke mimics on clinical
      grounds. Of the 41 acute stroke patients, 22 patients were deemed eligible for
      thrombolysis. Using multimodal CT imaging, 8 more patients were excluded from
      treatment because of lack of treatment target. Multimodal imaging failed to be
      obtained in one patient. For the 14 treated patients, median door-imaging time
      was 38min. Median door-treatment time was 91min. A 90-day mRS ?2 was achieved in
      40% of treated patients. We conclude that a telestroke service using advanced CT
      imaging for therapy decision assistance can be successfully implemented in
      regional Australia and can be used to guide acute stroke treatment decision
      making and improve access to thrombolytic therapy. Efficiency and safety is
      comparable to established telestroke services.

PMID- 27887974
TI  - Perusal of parasitic nematode 'omics in the post-genomic era.
AB  - The advent of high-throughput, next-generation sequencing methods combined with
      advances in computational biology and bioinformatics have greatly accelerated
      discovery within biomedical research. This "post-genomics" era has ushered in
      powerful approaches allowing one to quantify RNA transcript and protein abundance
      for every gene in the genome - often for multiple conditions. Herein, we
      chronicle how the post-genomics era has advanced our overall understanding of
      parasitic nematodes through transcriptomics and proteomics and highlight some of
      the important advances made in each major nematode clade. We primarily focus on
      organisms relevant to human health, given that nematode infections significantly
      impact disability-adjusted life years (DALY) scores within the developing world,
      but we also discuss organisms of veterinary importance as well as those used as
      laboratory models. As such, we envision that this review will serve as a
      comprehensive resource for those seeking a better understanding of basic
      parasitic nematode biology as well as those interested in targets for vaccination
      and pharmacological intervention.

PMID- 27887977
TI  - Direct and indirect cost of myasthenia gravis: A prospective study from a
      tertiary care teaching hospital in India.
AB  - Myasthenia gravis (MG) requires lifelong treatment. The cost of management MG is
      very high in developed countries but there is no information on the cost of
      management of MG in the developing countries. This study reports the direct and
      indirect cost and predictors of cost of MG in a tertiary care teaching hospital
      in India. In a prospective hospital based study, from a tertiary hospital in
      India 66 consecutive patient during 2014-2015 were included. The age of the
      patients ranged between 6 and 75years. The severity of MG was assessed by
      myasthenia gravis foundation association (MGFA) class (MGFA) I-V. The patient
      data was collected s and their direct cost was calculated from the computerized
      Hospital information system. The indirect cost was calculated from patient's
      memory, checking the bills of transportation and wages loss by the patient or the
      care giver. Total annual cost of MG ranged between INR (4560-532227) with median
      INR 61390.5 (US$911.64). The median cost of outpatient department (OPD)
      consultation of 16 patients was INR 20439.9 (US$303.53), of 50 admitted patients
      was INR 44311.8 (US$658.03) and 21 intensive care unit (ICU) patients was INR
      59574.3 (US$ 884.6) and the direct cost of thymectomy was INR 45000 (US$ 668.25).
      Direct cost was related to indirect cost (r=0.55; p=0.0001). Predictors of
      patient outcome were severity of MG, ICU admission, and thymectomy. The total
      median cost for management of myasthenia gravis was INR 61390.5 (4560-532227,
      US$911.64) per year, and the cost was mainly determined by the severity of MG.

PMID- 27887978
TI  - Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) due to
      dengue virus.
AB  - A 14-year-old girl presented with encephalopathy, delirium and ophthalmoplegia
      following a 3day history of high-grade fever. Brain MRI on day 6 of illness
      showed diffusion restricted ovoid lesion in the splenium of corpus callosum.
      Dengue virus encephalitis was diagnosed with positive PCR for dengue virus type-2
      in both serum and cerebrospinal fluid. She made a complete recovery from day 10
      of illness. Repeat brain MRI on day 12 of illness showed resolution of the
      splenial lesion. Serial diffusion tensor imaging (DTI) showed normal fractional
      anisotropy values on resolution of splenial lesion indicating that MERS was
      likely due to transient interstitial oedema with preservation of white matter
      tracts. This is the first reported case of MERS following dengue virus infection.
      It highlights the usefulness of performing serial DTI in understanding the
      underlying pathogenesis of MERS. Our case report widens the neurological
      manifestations associated with dengue infection and reiterates that patients with
      MERS should be managed supportively as the splenial white matter tracts are
      reversibly involved in MERS.

PMID- 27887979
TI  - Protective effect of nicotinamide adenine dinucleotide (NAD+) against spinal cord
      ischemia-reperfusion injury via reducing oxidative stress-induced neuronal
      apoptosis.
AB  - As previous studies demonstrate that oxidative stress and apoptosis play crucial
      roles in ischemic pathogenesis and nicotinamide adenine dinucleotide (NAD+)
      treatment attenuates oxidative stress-induced cell death among primary neurons
      and astrocytes as well as significantly reduce cerebral ischemic injury in rats.
      We used a spinal cord ischemia injury (SCII) model in rats to verify our
      hypothesis that NAD+ could ameliorate oxidative stress-induced neuronal
      apoptosis. Adult male rats were subjected to transient spinal cord ischemia for
      60min, and different doses of NAD+ were administered intraperitoneally
      immediately after the start of reperfusion. Neurological function was determined
      by Basso, Beattie, Bresnahan (BBB) scores. The oxidative stress level was
      assessed by superoxide dismutase (SOD) activity and malondialdehyde (MDA)
      content. The degree of apoptosis was analyzed by deoxyuridinetriphosphate nick
      end labeling (TUNEL) staining and protein levels of cleaved caspase-3 and AIF
      (apoptosis inducing factor). The results showed that NAD+ at 50 or 100mg/kg
      significantly decreased the oxidative stress level and neuronal apoptosis in the
      spinal cord of ischemia-reperfusion rats compared with saline, as accompanied
      with the decreased oxidative stress, NAD+ administration significantly restrained
      the neuronal apoptosis after ischemia injury while improved the neurological and
      motor function. These findings suggested that NAD+ might protect against spinal
      cord ischemia-reperfusion via reducing oxidative stress-induced neuronal
      apoptosis.

PMID- 27887980
TI  - The interaction between state and dispositional emotions in decision making: An
      ERP study.
AB  - In this study, to investigate the influence of incidental emotions on decision
      making in high-anxious individuals, participants were required to perform a
      monetary gambling task. Behavioral and electroencephalography responses were
      recorded to explore the stages of option assessment and outcome evaluation during
      decision making, respectively. Incidental emotions were elicited by facial
      expression pictures presented on the background, which included four conditions
      (control, neutral, fearful, and happy). Results showed smaller feedback-related
      negativity (FRN) amplitudes in high-anxious participants than low-anxious
      participants in the control, neutral, and fearful conditions, but not in the
      happy condition, for small outcomes. The P3 amplitudes were larger in high
      anxious participants compared to their counterparts in the fearful and happy
      conditions, but not in the other conditions. In short, the interaction effects
      between trait anxiety and facial emotions manifested on the outcome evaluation
      stage of decision making.

PMID- 27887981
TI  - Predictors of Mortality in the Critically Ill Cirrhotic Patient: Is the Model for
      End-Stage Liver Disease Enough?
AB  - BACKGROUND: Critically ill cirrhotics require liver transplantation urgently, but
      are at high risk for perioperative mortality. The Model for End-stage Liver
      Disease (MELD) score, recently updated to incorporate serum sodium, estimates
      survival probability in patients with cirrhosis, but needs additional evaluation
      in the critically ill. The purpose of this study was to evaluate the predictive
      power of ICU admission MELD scores and identify clinical risk factors associated
      with increased mortality. STUDY DESIGN: This was a retrospective review of
      cirrhotic patients admitted to the ICU between January 2011 and December 2014.
      Patients who were discharged or underwent transplantation (survivors) were
      compared with those who died (nonsurvivors). Demographic characteristics,
      admission MELD scores, and clinical risk factors were recorded. Multivariate
      regression was used to identify independent predictors of mortality, and measures
      of model performance were assessed to determine predictive accuracy. RESULTS: Of
      276 patients who met inclusion criteria, 153 were considered survivors and 123
      were nonsurvivors. Survivor and nonsurvivor cohorts had similar demographic
      characteristics. Nonsurvivors had increased MELD, gastrointestinal bleeding,
      infection, mechanical ventilation, encephalopathy, vasopressors, dialysis, renal
      replacement therapy, requirement of blood products, and ICU length of stay. The
      MELD demonstrated low predictive power (c-statistic 0.73). Multivariate analysis
      identified MELD score (adjusted odds ratio [AOR] = 1.05), mechanical ventilation
      (AOR = 4.55), vasopressors (AOR = 3.87), and continuous renal replacement therapy
      (AOR = 2.43) as independent predictors of mortality, with stronger predictive
      accuracy (c-statistic 0.87). CONCLUSIONS: The MELD demonstrated relatively poor
      predictive accuracy in critically ill patients with cirrhosis and might not be
      the best indicator for prognosis in the ICU population. Prognostic accuracy is
      significantly improved when variables indicating organ support (mechanical
      ventilation, vasopressors, and continuous renal replacement therapy) are included
      in the model.

PMID- 27887982
TI  - Genotypic resistance of cytomegalovirus to antivirals in hematopoietic stem cell
      transplant recipients from Portugal: A retrospective study.
AB  - The aim of this study was to characterize Human Cytomegalovirus (HCMV) drug
      resistance mutations in UL97 and UL54 genes in allogeneic hematopoietic stem cell
      transplant (allo-HSCT) recipients in Portugal. We have performed a retrospective
      study with 22 patients from a cohort of patients with different haematological
      malignancies submitted to allo-HSCT between 2010 and 2014. Patients were selected
      according to clinical and laboratory data of HCMV infection and management. HCMV
      resistance mutations were characterized by sequencing of UL97 and UL54 genes.
      Sequence data were compared with: 1) HCMV genome reference strain AD169; and also
      2) UL97 from Merlin strain (GenBank: AY446894.2), and UL54 from TB40/E strain
      (GenBank: ABV71585.1). Resistance mutations were identified in seven patients
      (32%): five harboured resistance mutations in UL97: A594V (n = 2), C592G (n = 1),
      L595W (n = 1), and C603W (n = 1); and two harboured resistance mutations in UL54:
      P522S and L957F, one in each patient. Several natural polymorphisms and unknown
      mutations were found in both UL97 and UL54, with the majority of the patients
      harbouring more than one unknown mutation in UL97 but only one in UL54. No
      simultaneous mutations were found. This is the first study in Portugal to
      characterize HCMV UL97 and UL54 sequences and to identify HCMV drug-resistance
      mutations in allo-HSCT patients. The UL97 resistance mutations found were amongst
      the most frequent resistant mutations, while UL54 L957F mutation was here
      reported for the first time in a clinical specimen. This information provides
      important information regarding HCMV strains and antiviral resistance in our
      population.

PMID- 27887983
TI  - Method of evaluating respiratory induced organ motion by vector volume histogram.
AB  - PURPOSE: Published organ motion data have been collected from measurements of a
      limited number of points within the organ, the centroid, or the edge of the
      organ. These are derived from the spatial characteristics of respiratory induced
      motion; however, this approach does not consider non-rigid organ deformation. We
      propose a novel quantitative method for evaluating respiratory induced organ
      motion using Deformable Image Registration (DIR). METHOD: Two phases from a 4
      dimensional computed tomography (4D CT) dataset at maximum inspiration and
      expiration were each taken from five patients. The left and right lungs,
      esophagus, stomach, spinal cord, and liver were manually contoured in the end
      expiration phase. The hybrid deformable registration algorithm of the RayStation
      treatment planning system (TPS) was used to deform the end-expiration phase to
      the end-inspiration phase. From this, the deformation vector field (DVF) was
      calculated. DVFs consist of DVFLR (left-right), DVFAP (anterior-posterior), and
      DVFSI (superior-inferior) as separate files. We calculated the vector volume
      histogram (VVH) and Lmax (maximum absolute vector of the organ) to evaluate every
      vector for each individual organ. We also measured respiratory organ motion from
      the position of the organ centroid in two phases. RESULTS: VVH enabled us to find
      the absolute distance and volume of the organ contributing to motion points on
      the curve. Organ motion using the centroid method was smaller than Lmax using
      VVH. Using the centroid method, it is difficult to evaluate the deformable organ
      motion. CONCLUSION: VVH may be a useful technique in evaluating organ volumetric
      change during respiratory organ motion.

PMID- 27887984
TI  - Impact of beta-hydroxy beta-methylbutyrate (HMB) on age-related functional
      deficits in mice.
AB  - beta-Hydroxy beta-methylbutyrate (HMB) is a metabolite of the essential amino
      acid leucine. Recent studies demonstrate a decline in plasma HMB concentrations
      in humans across the lifespan, and HMB supplementation may be able to preserve
      muscle mass and strength in older adults. However, the impact of HMB
      supplementation on hippocampal neurogenesis and cognition remains largely
      unexplored. The purpose of this study was to simultaneously evaluate the impact
      of HMB on muscle strength, neurogenesis and cognition in young and aged mice. In
      addition, we evaluated the influence of HMB on muscle-resident mesenchymal
      stem/stromal cell (Sca-1+CD45-; mMSC) function to address these cells potential
      to regulate physiological outcomes. Three month-old (n=20) and 24 month-old
      (n=18) female C57BL/6 mice were provided with either Ca-HMB or Ca-Lactate in a
      sucrose solution twice per day for 5.5weeks at a dose of 450mg/kg body weight.
      Significant decreases in relative peak and mean force, balance, and neurogenesis
      were observed in aged mice compared to young (age main effects, p<=0.05). Short
      term HMB supplementation did not alter activity, balance, neurogenesis, or
      cognitive function in young or aged mice, yet HMB preserved relative peak force
      in aged mice. mMSC gene expression was significantly reduced with age, but HMB
      supplementation was able to recover expression of select growth factors known to
      stimulate muscle repair (HGF, LIF). Overall, our findings demonstrate that while
      short-term HMB supplementation does not appear to affect neurogenesis or
      cognitive function in young or aged mice, HMB may maintain muscle strength in
      aged mice in a manner dependent on mMSC function.

PMID- 27887985
TI  - Insulin-like growth factor-1 protects SH-SY5Y cells against beta-amyloid-induced
      apoptosis via the PI3K/Akt-Nrf2 pathway.
AB  - Insulin-like growth factor-1 (IGF-1) shows protective effect against Abeta
      induced cytotoxicity and apoptosis, but the underlying mechanisms are poorly
      characterized. The present study was conducted to explore the mechanisms involved
      in the beneficial effect of IGF-1 against Abeta-induced apoptosis in SH-SY5Y
      cells. We found that pretreatment with IGF-1 attenuated Abeta25-35-induced loss
      of cell viability and apoptosis in SH-SY5Y cells in a dose-dependent manner. In
      addition, IGF-1 inhibited the generation of reactive oxygen species (ROS) and
      increased the antioxidant activity in Abeta25-35-treated cells. Further, IGF-1
      significantly promoted the nuclear translocation of Nrf2, and upregulated the
      expression of its downstream gene heme oxygenase-1 (HO-1). Moreover, LY294002, a
      specific PI3K inhibitor, was found to completely abolish the protective effect of
      IGF-1 on Abeta25-35-induced apoptosis and ROS generation. Together, our findings
      suggest that IGF-1 protects SH-SY5Y cells against Abeta25-35-induced cell injury
      by scavenging ROS via the PI3K/Akt-Nrf2 signaling pathway.

PMID- 27887986
TI  - Isolation of bacterial compartments to track movement of protein synthesis
      factors.
AB  - Aminoacyl-tRNA synthetases (AARSs) comprise an enzyme family that generates and
      maintains pools of aminoacylated tRNAs, which serve as essential substrates for
      protein synthesis. Many protein synthesis factors, including tRNA and AARSs also
      have non-canonical functions. Particularly in mammalian cells, alternate
      functions of AARSs have been associated with re-distribution in the cell to sites
      that are removed from translation. Sub-fractionation methods for E. coli were
      designed and optimized to carefully investigate re-localization of bacterial
      AARSs and tRNA that might aid in conferring alternate activities. Cell
      fractionation included isolation of the cytoplasm, periplasm, membrane, outer
      membrane vesicles, and extracellular media. Specific endogenous proteins and RNAs
      were probed respectively within each fraction via Western blots using antibodies
      and by Northern blots with primers to unique regions of the nucleic acid.

PMID- 27887987
TI  - Structural characterization of human aminoacyl-tRNA synthetases for translational
      and nontranslational functions.
AB  - Aminoacyl-tRNA synthetases (aaRSs) are enzymes that function at the first step of
      translation, catalyzing the conjugation of amino acids to their cognate tRNAs for
      protein synthesis. While preserving this essential role, higher eukaryotic aaRSs,
      such as human cytoplasmic aaRSs, have developed other functions during evolution,
      including angiogenesis, inflammation, development, tumorigenesis, etc. These
      translational and nontranslational functions of aaRSs are attractive targets for
      developing antibacterial, antifungal, anticancer agents and for treating other
      human diseases. Structural characterization of aaRS functions in both categories
      has deepened our understanding and provided insightful platform for further
      structure-based drug design. The convergence of the mechanism of action, together
      with their divergent functions, offers a possible protocol for studying these
      features of aaRSs in general. To guide this objective in future, we provide here
      a review on the methods used in structural analysis, which may be applied to
      study this special group of housekeeping proteins.

PMID- 27887988
TI  - In vitro and in vivo delivery of therapeutic proteins using cell penetrating
      peptides.
AB  - The failure of proteins to penetrate mammalian cells or target tumor cells
      restricts their value as therapeutic tools in a variety of diseases such as
      cancers. Recently, protein transduction domains (PTDs) or cell penetrating
      peptides (CPPs) have been shown to promote the delivery of therapeutic proteins
      or peptides into live cells. The successful delivery of proteins mainly depends
      on their physicochemical properties. Although, linear cell penetrating peptides
      are one of the most effective delivery vehicles; but currently, cyclic CPPs has
      been developed to potently transport bioactive full-length proteins into cells.
      Up to now, several small protein transduction domains from viral proteins
      including Tat or VP22 could be fused to other peptides or proteins to entry them
      in various cell types at a dose-dependent approach. A major disadvantage of PTD
      fusion proteins is primary uptake into endosomal vesicles leading to inefficient
      release of the fusion proteins into the cytosol. Recently, non-covalent complex
      formation (Chariot) between proteins and CPPs has attracted a special interest to
      overcome some delivery limitations (e.g., toxicity). Many preclinical and
      clinical trials of CPP-based delivery are currently under evaluation. Generally,
      development of more efficient protein transduction domains would significantly
      increase the potency of protein therapeutics. Moreover, the synergistic or
      combined effects of CPPs with other delivery systems for protein/peptide drug
      delivery would promote their therapeutic effects in cancer and other diseases. In
      this review, we will describe the functions and implications of CPPs for
      delivering the therapeutic proteins or peptides in preclinical and clinical
      studies.

PMID- 27887989
TI  - Quantitative PET image reconstruction employing nested expectation-maximization
      deconvolution for motion compensation.
AB  - Bulk body motion may randomly occur during PET acquisitions introducing blurring,
      attenuation-emission mismatches and, in dynamic PET, discontinuities in the
      measured time activity curves between consecutive frames. Meanwhile, dynamic PET
      scans are longer, thus increasing the probability of bulk motion. In this study,
      we propose a streamlined 3D PET motion-compensated image reconstruction (3D-MCIR)
      framework, capable of robustly deconvolving intra-frame motion from a static or
      dynamic 3D sinogram. The presented 3D-MCIR methods need not partition the data
      into multiple gates, such as 4D MCIR algorithms, or access list-mode (LM) data,
      such as LM MCIR methods, both associated with increased computation or memory
      resources. The proposed algorithms can support compensation for any periodic and
      non-periodic motion, such as cardio-respiratory or bulk motion, the latter
      including rolling, twisting or drifting. Inspired from the widely adopted point
      spread function (PSF) deconvolution 3D PET reconstruction techniques, here we
      introduce an image-based 3D generalized motion deconvolution method within the
      standard 3D maximum-likelihood expectation-maximization (ML-EM) reconstruction
      framework. In particular, we initially integrate a motion blurring kernel,
      accounting for every tracked motion within a frame, as an additional MLEM
      modeling component in the image space (integrated 3D-MCIR). Subsequently, we
      replaced the integrated model component with a nested iterative Richardson-Lucy
      (RL) image-based deconvolution method to accelerate the MLEM algorithm
      convergence rate (RL-3D-MCIR). The final method was evaluated with realistic
      simulations of whole-body dynamic PET data employing the XCAT phantom and real
      human bulk motion profiles, the latter estimated from volunteer dynamic MRI
      scans. In addition, metabolic uptake rate Ki parametric images were generated
      with the standard Patlak method. Our results demonstrate significant improvement
      in contrast-to-noise ratio (CNR) and noise-bias performance in both dynamic and
      parametric images. The proposed nested RL-3D-MCIR method is implemented on the
      Software for Tomographic Image Reconstruction (STIR) open-source platform and is
      scheduled for public release.

PMID- 27887990
TI  - WITHDRAWN: The new approach of multiple genome sequence parallel matching based
      on GPU.
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- 27887991
TI  - VCP/p97 regulates beta2AR quality control during receptor biosynthesis.
AB  - GPCRs form signalling complexes with other receptors as part of dimers, G
      proteins and effector partners. A proteomic screen to identify proteins that
      associate with the beta2-adrenergic receptor (beta2AR) identified many of
      components of the Endoplasmic-Reticulum-Associated Degradation (ERAD) quality
      control system [1], including the valosin-containing protein (VCP/p97). Here, we
      validated the interaction of VCP with co-expressed FLAG-beta2AR, demonstrating,
      using an inducible expression system, that the interaction of FLAG-beta2AR and
      VCP is not an artifact of overexpression of the beta2AR per se. We knocked down
      VCP and noted that levels of FLAG-beta2AR were increased in cells with lower VCP
      levels. This increase in the level of FLAG-beta2AR did not lead to an increase in
      the level of functional receptor observed at the cell surface. Similarly,
      inhibition of the proteasome lead to a dramatic increase in the abundance of TAP
      beta2AR, while cellular responses again remained unchanged. Taken together, our
      data suggests that a substantial proportion of the beta2AR produced is non
      functional and VCP plays a key role in the maturation and trafficking of the
      beta2AR as part of the ERAD quality control process.

PMID- 27887993
TI  - ISG15: In Sickness and in Health.
AB  - ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with
      pleiotropic functions, acting both as a soluble molecule and as a protein
      modifier. Surprisingly, and despite the antiviral functions of ISG15 described in
      mice, humans born with inactivating mutations of ISG15 do not present with any
      overt viral phenotype, but are highly susceptible to environmental mycobacteria
      and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also
      leads to persistently high levels of type I IFN-stimulated gene expression and to
      increased resistance to all viruses tested to date. This suggests that ISG15
      deficiency increases antiviral responses in humans, in stark contrast to
      expectations based on mouse experiments. We discuss here the roles of each of the
      forms of ISG15 in health and disease, as well as the differences between species.

PMID- 27887992
TI  - Does elevated progesterone on day of oocyte maturation play a role in the racial
      disparities in IVF outcomes?
AB  - The aim of this study was to evaluate if premature progesterone elevation on the
      last day of assisted reproduction technique stimulation contributes to racial
      disparities in IVF outcome. A total of 3289 assisted reproduction technique
      cycles were evaluated in Latino, Asian, African American, and white women. Live
      birth was more likely in white women (42.6%) compared with Asian (34.8%) and
      African American women (36.3%), but was similar to Latino women (40.7%). In all
      racial groups, progesterone was negatively associated with live birth and the
      negative effect of progesterone persisted when adjusting for confounders.
      Although the effect of elevated progesterone was similar in all racial groups,
      the prevalence of elevated progesterone differed. Progesterone > 1.5 ng/ml
      occurred in only 10.6% of cycles in white women compared with 18.0% in Latino and
      20.2% in Asian women. Progesterone > 2 ng/ml occurred in only 2.3% of cycles in
      white women compared with 6.3% in Latino, 5.9% in Asian and 4.4% in African
      American women. The increased prevalence of premature elevated progesterone
      persisted when controlling for IVF stimulation parameters. In conclusion,
      premature progesterone elevation had a negative effect on live birth in all
      racial groups studied. The prevalence of elevated progesterone was higher in
      racial minorities.

PMID- 27887994
TI  - Tactile stimulation during sleep alters slow oscillation and spindle densities
      but not motor skill.
AB  - Studies using targeted memory reactivation have shown that presentation of
      auditory or olfactory contextual cues during sleep can bias hippocampal
      reactivations towards the preferential replay of the cue-associated material,
      thereby resulting in enhanced consolidation of that information. If the same
      cortical ensembles are indeed used for encoding and storage of a given piece of
      information, forcing the sleeping brain to re-engage in task-intrinsic
      information processing should disturb the natural ongoing consolidation processes
      and therefore impair possible sleep benefits. Here we aimed at recreating an
      integral part of the sensory experience of a motor skill in a daytime nap, by
      means of a tactile stimulation. We hypothesized that tampering with the tactile
      component of a motor skill during sleep would result in hindered performance at
      retest, due to interference between the highly congruent incoming stimuli and the
      core skill trace. Contrary to our predictions, the tactile stimulation did not
      influence neither speed nor accuracy, when compared to natural sleep. However, an
      exploratory sleep EEG analysis revealed stimulation-induced alterations in the
      abundance and cortical topography of slow oscillations and spindles. These
      findings suggest that despite the lack of a significant effect on motor behavior,
      tactile stimulation induced changes in EEG features suggestive of a possible
      uncoupling between the sleep oscillations thought to underlie consolidation
      processes, i.e. slow oscillations and sleep spindles.

PMID- 27887995
TI  - Chronic stress and hippocampal dendritic complexity: Methodological and
      functional considerations.
AB  - The current understanding of how chronic stress impacts hippocampal dendritic
      arbor complexity and the subsequent relationship to hippocampal-dependent spatial
      memory is reviewed. A surge in reports investigating hippocampal dendritic
      morphology is occurring, but with wide variations in methodological detail being
      reported. Consequently, this review systematically outlines the basic
      neuroanatomy of relevant hippocampal features to help clarify how chronic stress
      or glucocorticoids impact hippocampal dendritic complexity and how these changes
      occur in parallel with spatial cognition. Chronic stress often leads to
      hippocampal CA3 apical dendritic retraction first with other hippocampal regions
      (CA3 basal dendrites, CA1, dentate gyrus, DG) showing dendritic retraction when
      chronic stress is sufficiently robust or long lasting. The stress-induced
      reduction in hippocampal CA3 apical dendritic arbor complexity often coincides
      with impaired hippocampal function, such as spatial learning and memory. Yet,
      when chronic stress ends and a post-stress recovery period ensues, the atrophied
      dendritic arbors and poor spatial abilities often improve. However, this process
      differs from a simple reversal of chronic stress-induced deficits. Recent reports
      suggest that this return to baseline-like functioning is uniquely different from
      non-stressed controls, emphasizing the need for further studies to enhance our
      understanding of how a history of stress subsequently alters an organism's
      spatial abilities. To provide a consistent framework for future studies, this
      review concludes with an outline for a quick and easy reference on points to
      consider when planning chronic stress studies with the goal of measuring
      hippocampal dendritic complexity and spatial ability.

PMID- 27887996
TI  - Effects of erythropoietin on neonatal hypoxia-ischemia brain injury in rat model.
AB  - BACKGROUND: Hypoxic-ischemic (HI) injury to the developing brain remains a major
      cause of morbidity. To date, few therapeutic strategies could provide complete
      neuroprotection. Erythropoietin (EPO) has been shown to be beneficial in several
      models of neonatal HI. This study examines the effect of treatment with
      erythropoietin on postnatal day 2 (P2) rats introduced with HI injury. METHOD:
      Rats at P2 were randomized into four groups: sham, bilateral carotid artery
      occlusion (BCAO), BCAO + early EPO, and BCAO + late EPO groups. Pups in each
      group were injected with either saline or EPO (5000U/kg) intraperitoneally once
      at immediately (early) or 48h (late) after HI induction. Body weight was assessed
      at P2 before and day 7 after HI. Mortality Rate was assessed at 24h, 48h and 72h
      after HI and brain water content was assessed at 72h. Brain weight and expression
      of myelin basic protein (MBP) were assessed at day 7 and day 14. At day 31 to 35
      following HI insult, neurological behavior function was assessed via Morris water
      maze (MWM) test. RESULT: HI cause significant higher mortality in male than in
      female (P=0.0445). Among the surviving animal, HI affect significantly the body
      growth, brain growth, MBP expression, and neurological behavior. EPO treatments
      at both early and late time points significantly benefit the rats in injury
      recovery, in which they promoted weight gains, reduced brain edema, as well as
      improved spatial learning ability and memory. CONCLUSION: We demonstrated a
      single dose of EPO at 5000U/kg immediately or 48h after HI injury had significant
      benefit for the P2 rats in injury recovery, and there was no adverse effect
      associated with either EPO treatment.

PMID- 27887997
TI  - A role for leptin-regulated neurocircuitry in subordination stress.
AB  - The visible burrow system produces a distinct combination of psychological and
      metabolic stress on, primarily, subordinate individuals that results in
      pronounced physiologic and behavioral dysfunction. However, the mechanisms
      underlying the consequences of chronic subordination stress are largely unknown.
      The simplest mechanistic explanation is that adaptations within brain systems
      with overlapping functions of both psychological and metabolic control provide
      immediate benefits that result in lasting susceptibility to diseases, disorders,
      and increased mortality rates in subordinates. Circuits regulated by leptin adapt
      to fluctuating levels of energy storage, such that the loss of leptin action
      within leptin-regulated neurocircuitry results in dysfunction in physiologic and
      behavioral systems implicated in the consequences of chronic social
      subordination. Thus, leptin-regulated neurocircuitry may provide a window into
      understanding the consequences of social subordination stress. This review
      examines the neural systems of leptin physiology implicated in social
      subordination stress: energy balance, motivation, HPA axis, and glycemic control.

PMID- 27887999
TI  - Rates and Technique for Oophoropexy in Pediatric Ovarian Torsion: A Single
      Institution Case Series.
AB  - STUDY OBJECTIVE: Ovarian torsion (OT) is uncommon, but can result in loss of
      reproductive function. Traditionally managed using adnexectomy, torsed adnexae
      are now being conserved, increasing the potential for recurrent OT. As a result,
      some experts suggest oophoropexy (OP) to prevent recurrence. We report on a
      series of 11 patients who underwent OP. DESIGN, SETTING, PARTICIPANTS,
      INTERVENTIONS, AND MAIN OUTCOME MEASURES: A retrospective case series was
      conducted from 2004 to 2013 to identify patients younger than the age of 18 years
      with OT. From this, data for patients with OP were extracted for detailed review.
      RESULTS: We identified 97 patients with OT; 6 of 97 (6.2%) had recurrent OT. The
      rate of recurrence was higher (14.8%, 4/27) in the group with torsion without an
      adnexal mass. Eleven of 97 patients (11.3%) underwent OP. The mean age of
      patients with OP was 8.8 years. Nine patients had normal adnexae at initial
      torsion. Five of 11 had OP during their initial procedure. OP was most commonly
      performed for long utero-ovarian ligaments (n = 6), recurrence (n = 4), or
      bilateral OT (n = 2). Eight of 8 patients with follow-up ultrasound imaging after
      torsion showed at least 1 marker of normal ovarian function. One of 11 patients
      (9%) had a recurrence of OT of an oophoropexied ovary. There were no
      complications due to the OP portion of the procedure. CONCLUSION: In our series
      of OT, a small percentage of patients underwent prophylactic OP. Recurrence might
      still occur after OP. It seems reasonable to offer OP to patients at higher risk
      of recurrent OT although level 1 evidence is lacking. Future research should
      focus on techniques and long-term outcomes of OP.

PMID- 27888000
TI  - Enhanced laboratory capacity development: a boost for effective tuberculosis
      control in resource-limited settings.
AB  - Both routine and research tuberculosis (TB) laboratory capacity urgently need to
      be expanded in large parts of Sub-Saharan Africa. In 2009, the Centre de
      Recherches Medicales de Lambarene (CERMEL) took a strategic decision to expand
      its activities by building TB laboratory capacity to address research questions
      and to improve routine diagnostic and treatment capacity. Over the past 7 years,
      a standard laboratory has been developed that is contributing significantly to TB
      diagnosis, treatment, and control in Gabon; training has also been provided for
      TB research staff in Central Africa. CERMEL has a cordial relationship with the
      Gabon National TB Control Programme (PNLT), which has culminated in a successful
      Global Fund joint application. This endeavour is considered a model for similar
      developments needed in areas of high TB prevalence and where TB control remains
      poor to date.

PMID- 27887998
TI  - The intricacies of the renin-angiotensin-system in metabolic regulation.
AB  - Over recent years, the renin-angiotensin-system (RAS), which is best-known as an
      endocrine system with established roles in hydromineral balance and blood
      pressure control, has emerged as a fundamental regulator of many additional
      physiological and pathophysiological processes. In this manuscript, we celebrate
      and honor Randall Sakai's commitment to his trainees, as well as his contribution
      to science. Scientifically, Randall made many notable contributions to the
      recognition of the RAS's roles in brain and behavior. His interests, in this
      regard, ranged from its traditionally-accepted roles in hydromineral balance, to
      its less-appreciated functions in stress responses and energy metabolism. Here we
      review the current understanding of the role of the RAS in the regulation of
      metabolism. In particular, the opposing actions of the RAS within adipose tissue
      vs. its actions within the brain are discussed.

PMID- 27888001
TI  - Antioxidants and HNE in redox homeostasis.
AB  - Under physiological conditions, cells are in a stable state known as redox
      homeostasis, which is maintained by the balance between continuous ROS/RNS
      generation and several mechanisms involved in antioxidant activity. ROS
      overproduction results in alterations in the redox homeostasis that promote
      oxidative damage to major components of the cell, including the biomembrane
      phospholipids. Lipid peroxidation subsequently generates a diverse set of
      products, including alpha,beta-unsaturated aldehydes. Of these products, 4
      hydroxy-2-nonenal (HNE) is the most studied aldehyde on the basis of its
      involvement in cellular physiology and pathology. This review summarizes the
      current knowledge in the field of HNE generation, metabolism, and detoxification,
      as well as its interactions with various cellular macromolecules (protein,
      phospholipid, and nucleic acid). The formation of HNE-protein adducts enables HNE
      to participate in multi-step regulation of cellular metabolic pathways that
      include signaling and transcription of antioxidant enzymes, pro-inflammatory
      factors, and anti-apoptotic proteins. The most widely described roles for HNE in
      the signaling pathways are associated with its activation of kinases, as well as
      transcription factors that are responsible for redox homeostasis (Ref-1, Nrf2,
      p53, NFkappaB, and Hsf1). Depending on its level, HNE exerts harmful or
      protective effects associated with the induction of antioxidant defense
      mechanisms. These effects make HNE a key player in maintaining redox homeostasis,
      as well as producing imbalances in this system that participate in aging and the
      development of pathological conditions.

PMID- 27888002
TI  - Polymorphisms in MIR499A and MIR125A gene are associated with autoimmune thyroid
      diseases.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) of the miR-146a, miR-499a and
      miR-125a have been shown to be associated with the susceptibility to several
      autoimmune diseases. This study was conducted to identify the association of SNPs
      rs2910164, rs57095329, rs3746444 and rs12976445 with autoimmune thyroid diseases
      (AITDs) in a Chinese Han population. METHODS: We enrolled 1061 patients with
      AITDs, including 701 patients with Graves' disease (GD) and 360 patients with
      Hashimoto's thyroiditis (HT), and 938 healthy individuals for a case-control
      genetic association study. Four SNPs were selected for genotyping by multiplex
      polymerase chain reaction and ligase detection reaction. RESULTS: The frequencies
      of rs3746444 genotypes in patients with AITD and GD differed significantly from
      those in the controls. The frequencies of rs12976445 genotypes in patients with
      HT differed significantly from those in the controls. The frequencies of allele C
      in HT groups were significantly higher than those in control group. For the
      rs3746444 polymorphism, genetic associations between the combinational genotype
      and AITD/GD risk were observed in the dominant model, recessive model, and
      overdominant model. For the rs12976445 polymorphism, genetic associations between
      the combinational genotype and HT risk were also found in the dominant model and
      overdominant model. Moreover, gene-sex interactions were identified by GMDR and 2
      * 2 crossover analysis. CONCLUSIONS: Our results suggest rs3746444 (miR-499a) and
      rs12976445 (miR-125a) associated with AITD susceptibility and potential gene-sex
      interactions between the four polymorphisms and AITD.

PMID- 27888003
TI  - Small non-coding RNAs-based bone regulation and targeting therapeutic strategies.
AB  - Small non-coding RNAs, which are 20-25 nucleotide ribonucleic acids, have emerged
      as an important transformation in the biological evolution over almost three
      decades. microRNAs (miRNAs) and short interfering RNAs (siRNAs) are two
      significant categories of the small RNAs that exert important effects on bone
      endocrinology and skeletology. Therefore, clarifying the expression and function
      of these important molecules in bone endocrine physiology and pathology is of
      great significance for improving their potential therapeutic value for metabolism
      associated bone diseases. In the present review, we highlight the recent advances
      made in understanding the function and molecular mechanism of these small non
      coding RNAs in bone metabolism, especially their potentially therapeutic values
      in bone-related diseases.

PMID- 27888004
TI  - Unliganded estrogen receptor alpha regulates vascular cell function and gene
      expression.
AB  - The unliganded form of the estrogen receptor is generally thought to be inactive.
      Our prior studies, however, suggested that unliganded estrogen receptor alpha
      (ERalpha) exacerbates adverse vascular injury responses in mice. Here, we show
      that the presence of unliganded ERalpha decreases vascular endothelial cell (EC)
      migration and proliferation, increases smooth muscle cell (SMC) proliferation,
      and increases inflammatory responses in cultured ECs and SMCs. Unliganded ERalpha
      also regulates many genes in vascular ECs and mouse aorta. Activation of ERalpha
      by E2 reverses the cell physiological effects of unliganded ERalpha, and promotes
      gene regulatory effects that are predicted to counter the effects of unliganded
      ERalpha. These results reveal that the unliganded form of ERalpha is not inert,
      but significantly impacts gene expression and physiology of vascular cells.
      Furthermore, they indicate that the cardiovascular protective effects of estrogen
      may be connected to its ability to counteract these effects of unliganded
      ERalpha.

PMID- 27888005
TI  - A simplified, semi-quantitative structural lung disease computed tomography
      outcome during quiet breathing in infants with cystic fibrosis.
AB  - Chest tomography (CT) using the controlled ventilation technique (CTCV) is a
      sensitive method to detect features of lung cystic fibrosis (CF) disease in
      infants with CF. However, this technique needs sedation and is not easily applied
      for the clinician who may need, in the follow-up, to evaluate more precisely lung
      disease in infants with CF. Thus, our study aims to evaluate if CT assessment of
      lung disease, without the need of sedation, during quiet breathing, using a semi
      quantitative scoring system, is reproducible and may discriminate infants with CF
      from control infants at an early stage of the lung disease. 39 infants with CF
      underwent a first CT at 10.3 [9.4, 11.4] weeks of age. Among them, 33 underwent a
      second CT at 56.1 [53.1, 59.6] weeks of age. CF scoring images of the different
      scanner variables, i.e. bronchial wall thickening, bronchiectasis, mucus plugging
      and air trapping were compared to CT scoring obtained in 2 different groups of
      control infants of similar age without lung disease. Among all the constituents
      of the scoring, air trapping is the only parameter discriminating infants with CF
      from control infants at both ages in our study (p<=0.01). Moreover, air trapping
      explains 90% of the total score variability with r2=0.89 with a good concordance
      after re-scoring in blind, 6months apart, by the same operator for both infant
      populations: ICC=0.98 [0.97, 0.99]. In this study, we propose that CT during
      quiet breathing could be a useful clinical tool to evaluate the early presence of
      gas trapping in infants with CF.

PMID- 27888006
TI  - Physicochemical characteristics and in vitro digestibility of potato and cassava
      starches under organic acid and heat-moisture treatments.
AB  - A combination of acid (citric acid or lactic acid) and heat-moisture treatment
      was used to modify cassava and potato starches in this study. Changes in
      physicochemical properties and in vitro digestibility of the treated starches
      were investigated. The cassava starch contained 17.0% amylose and possessed A
      type crystallinity, whereas the potato starch had 27.4% amylose and possessed B
      type crystallinity. After acid and heat-moisture treatment, the crystalline
      structure of the cassava starch remained unchanged (A type), while the
      crystalline structure of the potato starch changed from B type to the C (B+A)
      type. The acid and heat-moisture treatment increased gelatinization temperature,
      peak and final viscosities of cassava starch but reduced peak and breakdown
      viscosities of the potato starch. After acid and heat-moisture treatment, rapid
      digestible starch contents of the treated cassava and potato starches were
      significantly reduced. However, resistant starch (RS) contents of the treated
      starches significantly increased as compared to the native starches. Citric acid
      was found to have high impact on formation of RS in starches. The RS contents of
      cassava and potato starches obtained under the citric acid and heat-moisture
      treatment were 40.2% and 39.0%, respectively, two times higher than those of the
      native starches.

PMID- 27888007
TI  - HRI, a stress response eIF2alpha kinase, exhibits structural and functional
      stability at high temperature and alkaline conditions.
AB  - The Heme Regulated Inhibitor (HRI) is a key regulator of protein synthesis in
      mammalian cells. Once activated under heme-deficiency and other stress
      conditions, it phosphorylates the alpha subunit of eukaryotic initiation factor 2
      (eIF2alpha) leading to inhibition of protein synthesis. In the present study, our
      objective was to establish the structural and functional credentials of this
      kinase so as to qualify it as a stress responsive eIF2alpha kinase. When the
      catalytic kinase domain of the HRI (HRI.CKD) protein was subjected to high
      temperature, 45 degrees C (above mammalian heat shock temperature), it could
      still phosphorylate the substrate, indicating its potential as a stress response
      kinase. At a temperature beyond 45 degrees C, loss in secondary structure of the
      HRI.CKD is attributable to loss of its function. Furthermore, no significant
      structural changes were observed at the broad pH range of 3.0--10.0. The HRI.CKD
      incubated at any pH between 8.0-10.0, exhibited more than 60% of its kinase
      activity, demonstrating structural and functional stability of the kinase at an
      alkaline pH. These data taken together establish that the structural stability of
      this kinase at high temperature and alkaline conditions is due to conservation of
      its secondary structure and that the resulting functional activity qualifies this
      kinase as a stress responsive kinase.

PMID- 27888009
TI  - A novel approach for the chromatographic purification and peptide mass
      fingerprinting of urinary free light chains.
AB  - We describe a chromatographic approach for the purification of urinary free light
      chains (FLCs) viz., lambda free light chains (lambda-FLCs) and kappa free light
      chains (kappa-FLCs). Isolated urinary FLCs were analyzed by SDS-PAGE,
      immunoblotting and mass spectrometry (MS). The relative molecular masses of
      lambda-FLC and kappa-FLC are 22,933.397 and 23,544.336Da respectively. Moreover,
      dimer forms of each FLC were also detected in mass spectrum which corresponds to
      45,737.747 and 47,348.028Da respectively for lambda-FLCs and kappa-FLCs. Peptide
      mass fingerprint analysis of the purified lambda-FLCs and kappa-FLCs has yielded
      peptides that partially match with known light chain sequences viz., gi|218783338
      and gi|48475432 respectively. The tryptic digestion profile of isolated FLCs
      infers the exclusive nature of them and they may be additive molecules in the
      dictionary of urinary proteins. This is the first report of characterization and
      validation of FLCs from large volume samples by peptide sequencing. This simple
      and cost-effective approach to purification of FLCs, together with the easy
      availability of urine samples make the large-scale production of FLCs possible,
      allowing exploration of various bioclinical as well as biodiagnostic
      applications.

PMID- 27888008
TI  - Extracellular expression of alkali tolerant xylanase from Bacillus subtilis
      Lucky9 in E. coli and application for xylooligosaccharides production from agro
      industrial waste.
AB  - An alkali tolerant xylanase gene from Bacillus subtilis Lucky9 was cloned and
      extracellular expressed in E. coli BL21. Xylanase amino acid sequence showed 99%
      identity with xylanase sequence from Bacillus subtilis 168, and was belonged to
      glycoside hydrolase family 11. The recombinant E. coli (pET-pelB-xynLC9)
      containing pelB signal peptide produced extracellular xylanase of 436.5U/mL for
      8h, which was used arabinose as extra carbon source and inducer for enhancing
      extracellular production. The extracellular xylanase was determined by SDS-PAGE
      with a relative molecular mass of 21kDa. The recombinant xylanase was optimally
      activity at pH 6.5 and 60 degrees C. The xylanase exhibited 80% residual activity
      over a broad pH range of 6.0-9.0 for 24h. Thermostability studies showed that
      xylanase retained 60% residual activity after 2h at 60 degrees C. The main end
      products of hydrolysis of beech-wood xylan and corncob by the extracellular
      xylanase were xylobiose and xylotriose. This extracellular xylanase without
      purification is a suitable candidate for application in the industrial production
      of xylooligosaccharides from agro-industrial waste for use as prebiotics.

PMID- 27888010
TI  - Indole-3-acetic acid/diol based pH-sensitive biological macromolecule for
      antibacterial, antifungal and antioxidant applications.
AB  - Indole-3-acetic acid (IAA)/diol based pH-sensitive biopolymeric hydrogels with
      tunable biological properties (cytotoxicity, anti-oxidant and anti-fungal) have
      been synthesized via condensation polymerization. The present study focused on
      the synthesis of heterocyclic hydrogel using citric acid (CA), indole-3-acetic
      acid (IAA) and diethylene glycol (DEG) by condensation polymerization. The
      hydrogels revealed a pH-sensitive swelling behaviour, with increased swelling in
      acidic media, then turns to decreased the swelling in the basic media. The
      hydrogel samples were tested for antifungal activity against Aspergillus
      fumigates, Rhizopusoryzae and Candida albicans at different concentrations using
      ketoconazole as positive control and DMSO as negative control for antifungal
      activity. Antioxidant activity increasing nature in DPPH than NO radical compared
      with rutin and confirmed non toxic property using cytotoxicity analysis. The
      biopolymeric hydrogels were characterized by Fourier transform infrared (FT-IR)
      spectroscopy, 1H NMR,13C NMR, TGA, DSC followed by scanning electron microscopy
      (SEM). Such hydrogels with antioxidant properties is recommended for medical
      applications such as bandages, catheters, drains and tubes to prevent infection.

PMID- 27888012
TI  - Percutaneous Repair of a Complex Periprosthetic Aortic Leak.

PMID- 27888011
TI  - Antiproliferative and ultrastructural effects of phenethylamine derivatives on
      promastigotes and amastigotes of Leishmania (Leishmania) infantum chagasi.
AB  - Leishmania (Leishmania) infantum chagasi is one of the agents that cause visceral
      leishmaniasis. This disease occurs more frequently in third world countries, such
      as Brazil. The treatment is arduous, and is dependent on just a few drugs like
      the antimonial derivatives and amphotericin B. Moreover, these drugs are not only
      expensive, but they can also cause severe side effects and require long-term
      treatment. Therefore, it is very important to find new compounds that are
      effective against leishmaniasis. In the present work we evaluated a new group of
      synthetic amides against the promastigote and amastigote forms of L. infantum
      chagasi. The results showed that one of these amides in particular, presented
      very effective activity against the promastigotes and amastigotes of L. infantum
      chagasi at low concentrations and it also presented low toxicity for mammal
      cells, which makes this synthetic amide a promising drug for combating
      leishmaniasis.

PMID- 27888013
TI  - Epicardial Adipose Tissue in the General Middle-aged Population and Its
      Association With Metabolic Syndrome.
AB  - INTRODUCTION AND OBJECTIVES: There is currently increasing interest in epicardial
      adipose tissue (EAT) as a marker of cardiovascular disease. Our purpose was to
      describe EAT, measured by transthoracic echocardiography, and to assess its
      association with metabolic syndrome (MS) in the RIVANA population-based study.
      METHODS: Physical examination was performed in 880 participants aged 45 to 74
      years (492 of them with MS according to the harmonized definition). Fasting
      glucose, high-density lipoprotein cholesterol, triglyceride, and C-reactive
      protein concentrations were determined in a blood sample. In all participants,
      EAT thickness was measured with transthoracic echocardiography at end-systole.
      RESULTS: Among participants without MS, the prevalence of EAT >= 5mm
      significantly increased with age (OR > 65 years vs 45-54 years=8.22; 95%CI, 3.90
      17.35; P for trend<.001). Increasing EAT quintiles were significantly associated
      with MS (OR fifth quintile vs first quintile=3.26; 95%CI, 1.59-6.71; P for
      trend=.001). Considering the different MS criteria, increasing quintiles of EAT
      were independently associated with low high-density lipoprotein cholesterol (OR
      fifth quintile vs first quintile=2.65; 95%CI, 1.16-6.05; P for trend=.028), high
      triglycerides (OR fifth quintile vs first quintile=2.22; 95%CI, 1.26-3.90; P for
      trend=.003), and elevated waist circumference (OR fifth quintile vs first
      quintile=6.85; 95%CI, 2.91-16.11; P for trend<.001). CONCLUSIONS: In a subsample
      of the general population, EAT measured by echocardiography increased
      significantly and independently with age. Increased EAT thickness was
      independently associated with MS and with low high-density lipoprotein
      cholesterol, high triglycerides, and elevated waist circumference as individual
      criteria.

PMID- 27888015
TI  - Early and Long-Term Impaired T Lymphocyte Immune Reconstitution after Cord Blood
      Transplantation with Antithymocyte Globulin.
AB  - Immune reconstitution is crucial to the success of allogeneic hematopoietic stem
      cell transplantation. Umbilical cord blood transplantation (UCBT) has been
      associated with delayed immune reconstitution. We characterized the kinetics and
      investigated the risk variables affecting recovery of the main lymphocyte subsets
      in 225 consecutive pediatric and adult patients (males, n = 126; median age, 15;
      range, .3 to 60; interquartile range, 4 to 35) who underwent myeloablative single
      UCBT between 2005 and 2015 for malignant and nonmalignant disorders. Low CD4+ and
      CD8+ T cell counts were observed up to 12 months after UCBT. In contrast, B and
      natural killer cells recovered rapidly early after transplantation. In a
      multivariate regression model, factors favoring CD4+ T cell recovery >= 200
      cells/uL were lower dose antithymocyte globulin (ATG) (hazard ratio [HR], 3.93;
      95% confidence interval [CI], 2.3 to 5.83; P = .001), negative recipient
      cytomegalovirus (CMV) serostatus (HR, 3.76; 95% CI, 1.9 to 5.74; P = .001), and
      younger age (HR, 2.61; 95% CI, 1.01 to 3.47; P = .03). Factors favoring CD8+ T
      cell recovery >= 200 cells/uL were lower dose ATG (HR, 3.03; 95% CI, 1.4 to 5.1;
      P = .03) and negative recipient CMV serostatus (HR, 1.9; 95% CI, 1.63 to 2.15; P
      = .01). Our results demonstrate the significant negative impact of ATG on
      lymphocyte recovery. A reduction of the dose or omission of ATG could improve
      immune reconstitution and perhaps reduce opportunistic infections after UCBT.

PMID- 27888014
TI  - Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post
      Transplantation Cyclophosphamide for Pediatric and Young Adult Patients with High
      Risk Hematologic Malignancies.
AB  - Lower-intensity conditioning regimens for haploidentical blood or marrow
      transplantation (BMT) are safe and efficacious for adult patients with
      hematologic malignancies. We report data for pediatric/young adult patients with
      high-risk hematologic malignancies (n = 40) treated with nonmyeloablative
      haploidentical BMT with post-transplantation cyclophosphamide from 2003 to 2015.
      Patients received a preparative regimen of fludarabine, cyclophosphamide, and
      total body irradiation. Post-transplantation immunosuppression consisted of
      cyclophosphamide, mycophenolate mofetil, and tacrolimus. Donor engraftment
      occurred in 29 of 32 (91%), with median time to engraftment of neutrophils
      >500/uL of 16 days (range, 13 to 22) and for platelets >20,000/uL without
      transfusion of 18 days (range, 12 to 62). Cumulative incidences of acute graft
      versus-host disease (GVHD) grades II to IV and grades III and IV at day 100 were
      33% and 5%, respectively. The cumulative incidence of chronic GVHD was 23%, with
      7% moderate-to-severe chronic GVHD, according to National Institutes of Health
      consensus criteria. Transplantation-related mortality (TRM) at 1 year was 13%.
      The cumulative incidence of relapse at 2 years was 52%. With a median follow-up
      of 20 months (range, 3 to 148), 1-year actuarial overall and event-free survival
      were 56% and 43%, respectively. Thus, we demonstrate excellent rates of
      engraftment, GVHD, and TRM in pediatric/young adult patients treated with this
      regimen. This approach is a widely available, safe, and feasible option for
      pediatric and young adult patients with high-risk hematologic malignancies,
      including those with a prior history of myeloablative BMT and/or those with
      comorbidities or organ dysfunction that preclude eligibility for myeloablative
      BMT.

PMID- 27888017
TI  - Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary
      diffuse large B cell lymphoma cells through interleukin 10 pathway.
AB  - Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by
      the malignant transformation of B cells. Although it has been established that
      the follicular helper T (Tfh) cells play a central role in B cell development,
      little information is available on their involvement in DLBCL pathogenesis. We
      studied the role of the peripheral Tfh equivalent, the CXCR5+ CD4+ T cells, in
      DLBCL. Data showed that compared to CXCR5- CD4+ T cells, CXCR5+ CD4+ T cells were
      significantly more effective at promoting the proliferation as well as inhibiting
      the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found
      that at equal cell numbers, CXCR5+ CD4+ T cells in DLBCL patients secreted
      significantly less interleukin (IL)-21 than CXCR5- CD4+ T cells, while the level
      of IL-10 secretion was significant elevated in the CXCR5+ compartment compared to
      the CXCR5- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5+ CD4+
      T cell coculture compromised the CXCR5+ CD4+ T cell-mediated pro-tumor effects,
      in a manner that was dependent on the concentration of anti-IL-10 antibodies. The
      CXCR5+ compartment also contained significantly lower frequencies of cytotoxic
      CD4+ T cells than the CXCR5- compartment. In conclusion, our investigations
      discovered a previously unknown pro-tumor role of CXCR5-expressing circulating
      CD4+ T cells, which assisted the survival and proliferation of primary DLBCL
      cells through IL-10.

PMID- 27888016
TI  - Post-Transplantation Cyclophosphamide and Ixazomib Combination Rescues Mice
      Subjected to Experimental Graft-versus-Host Disease and Is Superior to Either
      Agent Alone.
AB  - Lapses in the prevention of graft-versus-host disease (GVHD) after allogeneic
      hematopoietic stem cell transplantation (HSCT) warrant novel approaches. Such
      approaches include, among others, the use of post-transplantation
      cyclophosphamide (PTC) and proteasome inhibitors. Although PTC alone consistently
      produces low rates of chronic GVHD, the incidence of acute GVHD remains
      significant. Inversely, prolonged post-transplantation administration of
      proteasome inhibitors carries a risk of paradoxical aggravation of GVHD. We
      examined whether the combination of cyclophosphamide and ixazomib addresses the
      limitations of each of these agents when used alone to prevent GVHD in mice
      subjected to allogeneic HSCT across MHC barriers. We chose ixazomib, an orally
      bioavailable proteasome inhibitor, because of its favorable physiochemical
      characteristics. The combination of cyclophosphamide and ixazomib improved
      overall survival of mice in comparison to an untreated control group and to
      groups receiving either cyclophosphamide alone or ixazomib alone. Furthermore,
      cyclophosphamide prevented the surge of IL-1beta, GVHD aggravation, and sudden
      death associated with prolonged administration of ixazomib after HSCT. Finally,
      we demonstrated that although ixazomib was administered before cyclophosphamide,
      it did not impair the preferential depletion of proliferating as opposed to
      resting donor T cells. Our data suggest that the combination of cyclophosphamide
      and ixazomib for the prevention of GVHD after allogeneic HSCT is promising and
      merits further investigation in clinical trials.

PMID- 27888018
TI  - 1400W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive
      deficits by suppressing the induction of inducible nitric oxide synthase in rat
      cerebral cortex microglia.
AB  - Nitric oxide (NO) is involved in neuronal modifications, and overproduction of NO
      contributes to memory deficits after acute hypobaric hypoxia-reoxygenation. This
      study investigated the ability of the iNOS inhibitor 1400W to counteract spatial
      memory deficits following acute hypobaric hypoxia-reoxygenation, and to affect
      expression of NOS, NO, 3-NT and MDA production, and apoptosis in rat cerebral
      cortex. We also used primary rat microglia to investigate the effect of 1400W on
      expression of NOS, NO, 3-NT and MDA production, and apoptosis. Acute hypobaric
      hypoxia-reoxygenation impaired spatial memory, and was accompanied by activated
      microglia, increased iNOS expression, NO, 3-NT and MDA production, and neuronal
      cell apoptosis in rat cerebral cortex one day post-reoxygenation. 1400W treatment
      inhibited iNOS expression without affecting nNOS or eNOS. 1400W also reduced NO,
      3-NT and MDA production, and prevented neuronal cell apoptosis in cerebral
      cortex, in addition to reversing spatial memory impairment after acute hypobaric
      hypoxia-reoxygenation. Hypoxia-reoxygenation activated primary microglia, and
      increased iNOS and nNOS expression, NO, 3-NT, and MDA production, and apoptosis.
      Treatment with 1400W inhibited iNOS expression without affecting nNOS, reduced
      NO, 3-NT and MDA production, and prevented apoptosis in primary microglia. Based
      on the above findings, we concluded that the highly selective iNOS inhibitor
      1400W inhibited iNOS induction in microglial cells, and reduced generation of NO,
      thereby mitigating oxidative stress and neuronal cell apoptosis in the rat
      cerebral cortex, and improving the spatial memory dysfunction caused by acute
      hypobaric hypoxia-reoxygenation.

PMID- 27888020
TI  - Neural correlates of affective empathy and reinforcement learning in boys with
      conduct problems: fMRI evidence from a gambling task.
AB  - BACKGROUND: Conduct problems (CP) comprise abnormal behaviors associated with
      aberrant aspects of affective empathy as well as learning. However, behavioral
      measures for affective empathy are challenging, and previous results concerning
      learning in patients with CP are inconsistent. METHODS: Nineteen boys with CP and
      24 typically developing (TD) boys aged 11-17 years (M=14.34, SD=1.93)
      participated in the study. An ultimatum-game was applied in order to elicit the
      feeling of like or dislike towards the opponent for a subsequent gambling task,
      which was played by the opponents (OTHER-condition) and by the participants
      themselves (SELF-condition). Functional MRI data were recorded throughout the
      experiment. RESULTS: In accordance with the model of insensitivity to punishment,
      hypo-activation of the left amygdala, left anterior insula, ventral medial
      prefrontal cortex (MPFC), and bilateral temporo-parietal junction (TPJ) was
      observed as a response to losing in participants with CP during the SELF
      condition. Callous-unemotional (CU)-traits correlated negatively with activation
      of amygdala and right TPJ. During the OTHER-condition, TD participants showed
      activation in brain areas associated with theory of mind (right TPJ, left IFG),
      and affect regulation (right DLPFC) rather than areas associated with affective
      empathy. This pattern was not found in adolescents with CP. Moreover, and
      independently of individual characteristics of their opponents, adolescents with
      CP demonstrated reward-associated activation (ventral striatum) observing others
      win, which was positively correlated with CU-traits. This may be interpreted in
      line with the theory of reward dominance. CONCLUSIONS: The current study provides
      support for the theory of abnormal learning processing in adolescents with CP
      which yields implications for further research as well as clinical practice. The
      gambling task did not activate affective empathy networks, but was specific for
      cognitive empathy, inhibition, and affect regulation.

PMID- 27888022
TI  - Intentions and barriers toward breastfeeding among Jordanian mothers-A cross
      sectional descriptive study using quantitative method.
AB  - PROBLEM/BACKGROUND: Breastfeeding is very important for both mother and infant.
      Within Jordanian hospitals, intentions and barriers to breastfeeding have not
      been addressed effectively during preparing policies in routine antenatal care or
      in maternal and child health care. AIM: To identify the intentions and barriers
      toward breastfeeding among Jordanian mothers with a specific focus on women from
      low income circumstances. METHODS: A cross-sectional descriptive study using
      quantitative methods was adopted in this study. Data was collected via the
      Modified Infant Feeding Intention Scale (MIFIS). FINDINGS: Women reported that
      for the most part their intention to feed their babies was using formula milk.
      However, they reported a desire to breastfeed but this intention could be
      hindered due to limited social support and challenges related to work
      arrangements. Further, participants also reported concerns regarding perceived
      pain that breastfeeding may cause and concerns regarding changes in their body
      shape and weight as a result of breastfeeding. CONCLUSION: Views toward
      breastfeeding among Jordanian women are not homogeneous. Policymakers and nurse
      educators should be cognizant of findings from this study and use them as
      guidelines for decision making. Efforts to improve intention toward breastfeeding
      can be achieved through structured and targeted educational programs for women
      from low income circumstances, and by modifying policies concerning work
      conditions for mothers to enable them to breastfeed their babies.

PMID- 27888021
TI  - Heightened aggressive behavior in mice deficient in aldo-keto reductase 1a
      (Akr1a).
AB  - Aldehyde reductase (Akr1a) is involved in the synthesis of ascorbic acid (AsA)
      which may play a role in social behavior. In the current study, we performed
      analyses on Akr1a-deficient (Akr1a-/-) mice that synthesize about 10% as much AsA
      as wild-type mice from the viewpoint of intermale aggression. The use of the
      resident-intruder test revealed that the Akr1a-/- mice exhibited more aggressive
      phenotypes than wild-type control mice. Unexpectedly, however, the oral
      administration of additional AsA failed to reduce the aggressive behavior of
      Akr1a-/- mice, suggesting that the heightened aggression was independent of AsA
      biosynthesis. The findings also show that the plasma levels of corticosterone,
      but not serotonin and testosterone, were increased in the absence of Akr1a in
      mice, suggesting that the mice were highly stressed. These results suggest that
      Akr1a might be involved in the metabolism of steroids and other carbonyl
      containing compounds and, hence, the absence of Akr1a results in heightened
      aggression via a malfunction in a metabolic pathway.

PMID- 27888019
TI  - Ifenprodil infusion in agranular insular cortex alters social behavior and
      vocalizations in rats exposed to moderate levels of ethanol during prenatal
      development.
AB  - Moderate exposure to alcohol during development leads to subtle neurobiological
      and behavioral effects classified under the umbrella term fetal alcohol spectrum
      disorders (FASDs). Alterations in social behaviors are a frequently observed
      consequence of maternal drinking, as children with FASDs display inappropriate
      aggressive behaviors and altered responses to social cues. Rodent models of FASDs
      mimic the behavioral alterations seen in humans, with rats exposed to ethanol
      during development displaying increased aggressive behaviors, decreased social
      investigation, and altered play behavior. Work from our laboratory has observed
      increased wrestling behavior in adult male rats following prenatal alcohol
      exposure (PAE), and increased expression of GluN2B-containing NMDA receptors in
      the agranular insular cortex (AIC). This study was undertaken to determine if
      ifenprodil, a GluN2B preferring negative allosteric modulator, has a significant
      effect on social behaviors in PAE rats. Using a voluntary ethanol exposure
      paradigm, rat dams were allowed to drink a saccharin-sweetened solution of either
      0% or 5% ethanol throughout gestation. Offspring at 6-8 months of age were
      implanted with cannulae into AIC. Animals were isolated for 24h before ifenprodil
      or vehicle was infused into AIC, and after 15min they were recorded in a social
      interaction chamber. Ifenprodil treatment altered aspects of wrestling, social
      investigatory behaviors, and ultrasonic vocalizations in rats exposed to ethanol
      during development that were not observed in control animals. These data indicate
      that GluN2B-containing NMDA receptors in AIC play a role in social behaviors and
      may underlie alterations in behavior and vocalizations observed in PAE animals.

PMID- 27888023
TI  - Integrated process for the purification and immobilization of the envelope
      protein domain III of dengue virus type 2 expressed in Rachiplusia nu larvae and
      its potential application in a diagnostic assay.
AB  - Dengue incidence has grown dramatically in the last years, with about 40% of the
      world population at risk of infection. Recently, a vaccine developed by Sanofi
      Pasteur has been registered, but only in a few countries. Moreover, specific
      antiviral drugs are not available. Thus, an efficient and accurate diagnosis is
      important for disease management. To develop a low-cost immunoassay for dengue
      diagnosis, in the present study we expressed the envelope protein domain III of
      dengue virus type 2 in Rachiplusia nu larvae by infection with a recombinant
      baculovirus. The antigen was expressed as a fusion to hydrophobin I (DomIIIHFBI)
      to easily purify it by an aqueous two-phase system (ATPS) and to efficiently
      immobilize it in immunoassay plates. A high level of recombinant DomIIIHFBI was
      obtained in R. nu, where yields reached 4.5 mg per g of larva. Also, we were able
      to purify DomIIIHFBI by an ATPS with 2% of Triton X-114, reaching a yield of 73%
      and purity higher than 80% in a single purification step. The recombinant
      DomIIIHFBI was efficiently immobilized in hydrophobic surface plates. The
      immunoassay we developed with the immobilized antigen was able to detect IgG
      specific for dengue virus type 2 in serum samples and not for other serotypes.

PMID- 27888025
TI  - The Importance of Role Models in Increasing Women in Radiology.

PMID- 27888024
TI  - Performance of Photon-Counting Breast Computed Tomography, Digital Mammography,
      and Digital Breast Tomosynthesis in Evaluating Breast Specimens.
AB  - RATIONALE AND OBJECTIVES: This study compared a novel photon-counting breast
      computed tomography (pcBCT) system with digital mammography (DM) and digital
      breast tomosynthesis (DBT) systems. For this reason, surgical specimens were
      examined with all three techniques and rated by three observers. MATERIALS AND
      METHODS: A total of 30 surgical specimens were investigated with DM, DBT, and
      pcBCT; the associated images were shown to three experienced radiologists.
      Findings (22 microcalcifications and 23 mass lesions) were recorded and compared
      to the results of the pathological examination. Sensitivity and specificity for
      detection of microcalcifications and lesions were calculated and displayed using
      receiver operating characteristic curves. RESULTS: Sensitivity for
      microcalcifications was 82% for DM, 70% for DBT, and 85% for pcBCT. Specificity
      for microcalcifications was 71% for DM, 75% for DBT, and 83% for pcBCT.
      Sensitivity for lesions was 45% for DM, 62% for DBT, and 65% for pcBCT.
      Specificity for lesions was 76% for DM, 62% for DBT, and 76% for pcBCT.
      CONCLUSIONS: pcBCT showed a comparable or superior performance compared to the
      clinically approved DM and DBT systems. Mass lesion detectability can be
      increased further by the use of contrast media.

PMID- 27888026
TI  - TEMPORARY REMOVAL: Priming theta burst stimulation enhances motor cortex
      plasticity in young but not old adults.

PMID- 27888027
TI  - Can exhaled nitric oxide fraction predict adherence to inhaled corticosteroids in
      atopic and nonatopic children with asthma?

PMID- 27888028
TI  - Identifying Allergic Drug Reactions Through Placebo-Controlled Graded Challenges.
AB  - BACKGROUND: Graded challenges are performed to exclude hypersensitivity reactions
      in patients with a low likelihood of drug allergy. Literature regarding optimal
      protocols with a defined number of steps and use of placebo is lacking.
      OBJECTIVE: To identify allergic drug reactions (ADRs) through a 3-step protocol
      composed of placebo followed by a 2-step graded drug challenge. METHODS: We
      performed a 5-year retrospective chart review of all patients with historical
      ADRs who underwent single-blind, placebo-controlled graded drug challenges
      between October 2010 and November 2015 at an outpatient drug allergy clinic.
      Patients' demographic characteristics and description of historical reaction were
      obtained. Outcomes of challenges to drug versus placebo were compared by drug
      class. RESULTS: Two hundred twenty-nine patients underwent at least 1 single
      blind placebo-controlled graded challenge. The most commonly challenged drug
      class was beta-lactams (70.8%) followed by nonsteroidal anti-inflammatory drugs
      (17.5%). The reaction rate to drug and placebo was similar during beta-lactam
      challenges (9.4% vs 8.2%; P = .9) and during nonsteroidal anti-inflammatory drug
      challenges (14% vs 7%, P = .5), respectively. Only 10 patients (4.4%) had
      objective findings during drug challenges. Patients who reacted to placebo before
      beta-lactam challenges had an increased number of drug allergies (4.3 +/- 1.0)
      compared with nonreactors (2.4 +/- 0.1) and to beta-lactam reactors (3.3 +/- 0.7)
      (P = .002). All placebo reactors were female (20 of 183 vs 0 of 46 males; P =
      .02). CONCLUSIONS: Two-step graded challenges are safe in appropriately selected
      patients with a low risk of reaction. Placebo should be considered to reduce
      false-positive results, especially in females and in patients with multiple drug
      allergies.

PMID- 27888029
TI  - Drug-specific upregulation of CD137 on CD8+ T cells aids in the diagnosis of
      multiple antibiotic toxic epidermal necrolysis.

PMID- 27888030
TI  - Antrochoanal Polyp.

PMID- 27888031
TI  - Comparison of treatment modalities for inpatient asthma exacerbations among US
      pediatric hospitals.

PMID- 27888032
TI  - Allergy to benznidazole: cross-reactivity with other nitroimidazoles.

PMID- 27888033
TI  - Prenatal Intake of Vitamins and Allergic Outcomes in the Offspring: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Allergic diseases have seen a rise worldwide, with children suffering
      the highest burden. Thus, early prevention of allergic diseases is a public
      health priority. OBJECTIVE: To synthesize the evidence from randomized controlled
      trials (RCTs) assessing the effect of vitamin interventions during pregnancy on
      developing allergic diseases in offspring. METHODS: We searched CENTRAL, MEDLINE,
      SCOPUS, World Health Organization's International Clinical Trials Registration, E
      theses, and Web of Science. Study quality was evaluated using Cochrane's risk of
      bias tool. Included RCTs had a minimum of 1-month follow-up postgestation.
      RESULTS: A total of 5 RCTs met the inclusion criteria, including 2456 children
      who used vitamins C + E (1 study), vitamin C (1 study), and vitamin D (3 studies)
      compared with placebo/control. Two studies were judged to have a high risk of
      bias for performance bias or a high rate of loss to follow-up. All were rated as
      low risk of bias for blinding of outcome assessment. We did not perform meta
      analysis with vitamin C or vitamin C + E studies due to high heterogeneity
      between the 2 included studies. However, we did conduct a meta-analysis with
      trials on vitamin D (including 1493 children) and the results showed an
      association between the prenatal intake of vitamin D and the risk of developing
      recurrent wheeze in offspring (relative risk (RR), 0.812; 95% CI, 0.67-0.98).
      CONCLUSIONS: The current evidence suggests that prenatal supplementation of
      vitamin D might have a beneficial effect on recurrent wheezing in children.
      Longer-term follow-up of these studies is needed to ascertain whether this
      observed effect is sustained. There is lack of evidence on the effect of other
      vitamins for the prevention of respiratory and/or allergic outcomes.

PMID- 27888034
TI  - A Proactive Approach to Penicillin Allergy Testing in Hospitalized Patients.
AB  - BACKGROUND: Penicillin allergy testing is underutilized in inpatients despite its
      potential to immediately impact antibiotic treatment. Although most tested
      patients are able to tolerate penicillin, limited availability and awareness of
      this tool leads to the use of costly and harmful substitutes. OBJECTIVE: We
      established an inpatient service at a large academic hospital to identify and
      test patients with a history of penicillin allergy with the goals of removing
      inaccurate diagnoses, reducing the use of beta-lactam alternatives, and educating
      patients and clinicians about the procedure. METHODS: Eligible inpatients were
      flagged daily through the electronic medical record and prioritized via a
      specialized algorithm. A trained clinical pharmacist performed penicillin skin
      tests and challenges preemptively or by provider request. Clinical
      characteristics and antibiotic use were analyzed in tested patients. RESULTS: A
      total of 1203 applicable charts were detected by our system leading to 252 direct
      evaluations over 18 months. Overall, 228 subjects (90.5%) had their penicillin
      allergy removed. Of these, 223 were cleared via testing and 5 by discovery of
      prior penicillin tolerance. Among patients testing negative, 85 (38%)
      subsequently received beta-lactams, preventing 504 inpatient days and 648
      outpatient days on alternative agents. CONCLUSIONS: Penicillin allergy testing
      using a physician-pharmacist team model effectively removes reported allergies in
      hospitalized patients. The electronic medical record is a valuable asset for
      locating and stratifying individuals who benefit most from intervention.
      Proactive testing substantially reduces unnecessary inpatient and outpatient use
      of beta-lactam alternatives that may otherwise go unaddressed.

PMID- 27888036
TI  - Desensitization for immediate hypersensitivity to oral dimethyl fumarate
      (Tecfidera).

PMID- 27888035
TI  - Racial Differences in Food Allergy Phenotype and Health Care Utilization among US
      Children.
AB  - BACKGROUND: Food allergy (FA) is a prevalent condition in the United States, but
      little is known about its phenotypes in racial minority groups. OBJECTIVE: The
      objective of this study was to characterize disease phenotypes and disparities in
      health care utilization among African American (AA), Hispanic, and white children
      with FA. METHODS: We conducted a large, 2-center, retrospective cohort study of
      children aged 0-17 years with FA seen in allergy/immunology clinics at 2 urban
      tertiary care centers in the United States. We used multiple logistic regression
      analyses adjusted for age, gender, and insurance. RESULTS: The cohort of 817
      children was composed of 35% AA, 12% Hispanic, and 53% non-Hispanic white.
      Compared with non-Hispanic white children, AA children had significantly higher
      odds of having asthma and eczema (P < .01), and significantly higher odds of
      allergy to wheat, soy, corn, fish, and shellfish (P < .01). Compared with non
      Hispanic white children, Hispanic children had significantly higher odds of
      allergy to corn, fish, and shellfish (P < .01), and higher odds of eczema (P <
      .01), but a similar rate of asthma (P = .44). In this cohort, 55%, 18%, and 11%
      of AA, Hispanic, and white children were covered by Medicaid, respectively (P <
      .00001). Compared with whites, AA and Hispanic children had a shorter duration of
      follow-up for FA with an allergy specialist and higher rates of FA-related
      anaphylaxis and emergency department visits (P < .01). CONCLUSIONS: FA phenotypes
      and health care utilization differ among children of different racial and/or
      ethnic backgrounds in the United States that put AA and Hispanic children at
      higher risks of adverse outcome than white children. These differences include
      coexistent atopic conditions, less well recognized food allergens, and higher
      rates of anaphylaxis.

PMID- 27888037
TI  - Insights from parents can guide asthma care for urban, minority children.

PMID- 27888038
TI  - Evidence of bottleneck effect on hepatitis C virus transmission between a couple
      under interferon based therapy.
AB  - Issues on the correlation of viral genetic diversity and treatment response to
      the hepatitis C infection remain uncertain. The bottleneck effect dictates the
      characteristics of the viral population that will establish the infection in a
      new host and is related to how the immune system and treatment will be effective
      against the virus. Here we evaluated the phylogenetic characteristics of
      quasispecies population and the treatment response pattern of a HCV infected
      couple. We also analyzed whether the viral population of these patients indicated
      that they were exposed to the same source for primer infection. This study
      included two patients (P10 and P11) HCV genotype 1b infected. The couple
      presented horizontal transmission. Viral RNA was isolated from serum samples
      collected before, during and after treatment, at specific time points. The HCV
      NS5A gene sequence was amplified, cloned and sequenced. Genetic and evolutionary
      analyses were performed to compare the quasispecies population of these two
      patients and local control patients. Genetic distance and diversity were
      calculated. Phylogenetic analyses were performed by using maximum likelihood and
      Bayesian methodologies. The analysis of the baseline samples showed that the
      genetic distance of the viral populations of patients P10 and P11 was
      significantly lower than when these patients and the control group based on
      sequences from local patients were analyzed, supporting the horizontal
      transmission hypothesis. Phylogenetic analysis with sequences from all the time
      point samples also demonstrated two patterns of evolution depending on the
      treatment response. The Bayesian analysis showed that one isolate corresponding
      to the baseline sample of P10 was grouped into the P11 clade, suggesting a way of
      infection and a bottleneck effect. Our data suggests that the patient P11 viral
      population may be originated from variants from P10 patient and consequently
      showing that clinical differences between treatment responses can emerge from the
      bottleneck effect on viral populations.

PMID- 27888039
TI  - Total midgut volvulus in adults with intestinal malrotation. Report of eleven
      patients.
AB  - OBJECTIVE: Total small-intestinal volvulus with malrotation (TSIVM) classically
      presents in the neonatal period; it occurs much less frequently in the adult and
      is often misdiagnosed. Prognosis is directly related to the degree and duration
      of intestinal ischemia. Our goal is to describe our experience with TSIVM in the
      adult, to identify any specific findings and to discuss its management. METHOD:
      Eleven patients who had undergone surgery for TSIVM at three centers between 1992
      and 2012 were included. Surgery was performed as an emergency for five patients
      and surgery was elective for six. RESULTS: Mean follow-up was 63 months (range:
      12-270). Six patients had had previous abdominal surgery. In nine cases, the
      diagnosis of TSIVM was made preoperatively, mainly by CT scan in eight cases.
      Seven patients had associated congenital failure of retroperitoneal fixation of
      the right colon and all of these underwent a Ladd procedure. The mortality rate
      was zero. Of the five patients who underwent emergency surgery, three required
      intestinal resections, one of whom developed a short bowel syndrome. The six
      patients who underwent surgery electively had no surgical complications.
      CONCLUSION: TSIVM is a very unusual finding in adult patients. The diagnosis can
      be made by CT scan with IV and oral contrast, but it often comes to light only at
      the time of surgery, even though the patients have often had recurrent episodes
      of abdominal symptomatology that dated back to childhood. The Ladd procedure,
      consisting of division of Ladd's bands, widening of the mesentery, and incidental
      appendectomy, remains the standard surgical repair. Digestive surgeons who care
      for adults should be familiar with this procedure, and it should be performed, as
      often as possible, with the assistance of a pediatric surgeon.

PMID- 27888040
TI  - Evidence that hidden hearing loss underlies amplitude modulation encoding
      deficits in individuals with and without tinnitus.
AB  - Damage to auditory nerve fibers that expresses with suprathreshold sounds but is
      hidden from the audiogram has been proposed to underlie deficits in temporal
      coding ability observed among individuals with otherwise normal hearing, and to
      be present in individuals experiencing chronic tinnitus with clinically normal
      audiograms. We tested whether these individuals may have hidden synaptic losses
      on auditory nerve fibers with low spontaneous rates of firing (low-SR fibers)
      that are important for coding suprathreshold sounds in noise while high-SR fibers
      determining threshold responses in quiet remain relatively unaffected. Tinnitus
      and control subjects were required to detect the presence of amplitude modulation
      (AM) in a 5 kHz, suprathreshold tone (a frequency in the tinnitus frequency
      region of the tinnitus subjects, whose audiometric thresholds were normal to 12
      kHz). The AM tone was embedded within background noise intended to degrade the
      contribution of high-SR fibers, such that AM coding was preferentially reliant on
      low-SR fibers. We also recorded by electroencephalography the "envelope following
      response" (EFR, generated in the auditory midbrain) to a 5 kHz, 85 Hz AM tone
      presented in the same background noise, and also in quiet (both low-SR and high
      SR fibers contributing to AM coding in the latter condition). Control subjects
      with EFRs that were comparatively resistant to the addition of background noise
      had better AM detection thresholds than controls whose EFRs were more affected by
      noise. Simulated auditory nerve responses to our stimulus conditions using a well
      established peripheral model suggested that low-SR fibers were better preserved
      in the former cases. Tinnitus subjects had worse AM detection thresholds and
      reduced EFRs overall compared to controls. Simulated auditory nerve responses
      found that in addition to severe low-SR fiber loss, a degree of high-SR fiber
      loss that would not be expected to affect audiometric thresholds was needed to
      explain the results in tinnitus subjects. The results indicate that hidden
      hearing loss could be sufficient to account for impaired temporal coding in
      individuals with normal audiograms as well as for cases of tinnitus without
      audiometric hearing loss.

PMID- 27888041
TI  - Understanding the contributions of visual stimuli to contextual fear
      conditioning: A proof-of-concept study using LCD screens.
AB  - The precise contribution of visual information to contextual fear learning and
      discrimination has remained elusive. To better understand this contribution, we
      coupled the context pre-exposure facilitation effect (CPFE) fear conditioning
      paradigm with presentations of distinct visual scenes displayed on 4 LCD screens
      surrounding a conditioning chamber. Adult male Long-Evans rats received non
      reinforced context pre-exposure on Day 1, an immediate 1.5mA foot shock on Day 2,
      and a non-reinforced context test on Day 3. Rats were pre-exposed to either
      digital Context (dCtx) A, dCtx B, a distinct Ctx C, or no context on Day 1.
      Digital context A and B were identical except for the visual image displayed on
      the LCD screens. Immediate shock and retention testing occurred in dCtx A. Rats
      pre-exposed dCtx A showed the CPFE with significantly higher levels of freezing
      compared to controls. Rats pre-exposed to Context B failed to show the CPFE, with
      freezing that did not highly differ from controls. These results suggest that
      visual information contributes to contextual fear learning and that visual
      components of the context can be manipulated via LCD screens. Our approach offers
      a simple modification to contextual fear conditioning paradigms whereby the
      visual features of a context can be manipulated to better understand the factors
      that contribute to contextual fear discrimination and generalization.

PMID- 27888042
TI  - Changes in neurotrophic and inflammatory factors in the cerebrospinal fluid of
      patients with postherpetic neuralgia.
AB  - Inflammatory and neurotrophic factors are involved in postherpetic neuralgia
      (PHN), but the association of these factors in the cerebrospinal fluid (CSF) with
      the level of pain is poorly known. The present study aimed to examine the changes
      in neurotrophic and inflammatory factors in the CSF of patients with PHN and to
      study the correlation between these factors and the degree of pain. Fifty
      patients with PHN and 28 patients with hemifacial spasm (as controls) were
      recruited between May 2015 and March 2016. CSF levels of inflammatory and
      neurotrophic factors were measured by ELISA. Compared with controls, patients
      with PHN had lower CSF levels of brain-derived neurotrophic factor (BDNF), nerve
      growth factor (NGF), neurotrophin (NT)-3, NT-5, and P substance (all P<0.05), and
      higher CSF levels of interleukin (IL)-1beta (P=0.050). Among patients with PHN,
      CSF BDNF levels were positively correlated to IL-8 (rs=0.229, P=0.04); glial cell
      line-derived neurotrophic factor (GDNF) levels to IL-8 (rs=0.326, P=0.004)
      levels; NGF levels to tumor necrosis factor (TNF)-alpha levels (rs=0.229,
      P=0.044); NT-3 levels to IL-1beta (rs=0.228, P=0.045); and NT-5 levels to IL-8
      (rs=0.388, P<0.001), and TNF-alpha (rs=0.445, P<0.001) levels. Inflammatory and
      neurotrophic factors were not correlated with the visual analog scale score and
      von Frey. Multivariable linear regression showed PHN was associated with NGF
      (P=0.038) and BDNF (P=0.029), independently from age and major medical history.
      In conclusion, patients with PHN showed low levels of BDNF, NGF, NT-3, and NT-5.
      Among patients with PHN, CSF levels of neurotrophic factors positively correlated
      with inflammatory factors.

PMID- 27888043
TI  - Infusion of fluoxetine, a serotonin reuptake inhibitor, in the shell region of
      the nucleus accumbens increases blood glucose concentrations in rats.
AB  - The brain is well known to regulate blood glucose, and the hypothalamus and
      hindbrain, in particular, have been studied extensively to understand the
      underlying mechanisms. Nuclei in these regions respond to alterations in blood
      glucose concentrations and can alter glucose liver output or glucose tissue
      uptake to maintain blood glucose concentrations within strict boundaries.
      Interestingly, several cortico-limbic regions also respond to alterations in
      glucose concentrations and have been shown to project to hypothalamic nuclei and
      glucoregulatory organs. For instance, electrical stimulation of the shell of the
      nucleus accumbens (sNAc) results in increased circulating concentrations of
      glucose and glucagon and activation of the lateral hypothalamus (LH). Whether
      this is caused by the simultaneous increase in serotonin release in the sNAc
      remains to be determined. To study the effect of sNAc serotonin on systemic
      glucose metabolism, we implanted bilateral microdialysis probes in the sNAc of
      male Wistar rats and infused fluoxetine, a serotonin reuptake inhibitor, or
      vehicle after which blood glucose, endogenous glucose production (EGP) and
      glucoregulatory hormones were measured. Fluoxetine in the sNAc for 1h
      significantly increased blood glucose concentrations without an effect on
      glucoregulatory hormones. This increase was accompanied by a higher EGP in the
      fluoxetine infused rats compared to the controls. These data provide further
      evidence for a role of sNAc-serotonin in the regulation of glucose metabolism.

PMID- 27888044
TI  - Motor memory consolidation processes in young female adults with ADHD may be less
      susceptible to interference.
AB  - Young adults with Attention Deficit Hyperactivity Disorder (ADHD) may have an
      atypical procedural ("how to") memory consolidation phase, after practicing a
      movement sequence, with smaller gains in speed and some costs in accuracy,
      compared to typical peers, at 24h post-training. Here we tested the
      susceptibility of performance gains retained after motor practice by young female
      adults with (N=16) and without (N=16) ADHD to post-training interference.
      Participants were trained on the finger-to-thumb opposition sequence learning
      task with performance speed and accuracy recorded before training, immediately
      after, and at 24h post-training. Two hour after the initial training,
      participants practiced a second, similarly constructed but differently ordered
      sequence of movements. Typical young adults showed a significant interference
      effect, with only the performance of the second sequence showing robust gains in
      speed, with no costs in accuracy, in the 24h post-training consolidation phase.
      Participants with ADHD showed only small additional speed gains in the post
      training consolidation phase but for both sequences. Altogether these results
      suggest that motor memory consolidation processes in young adults with ADHD may
      be less susceptible to interference compared to typical peers.

PMID- 27888045
TI  - Effects of tiotropium on lung function in current smokers and never smokers with
      bronchial asthma.
AB  - The effects of tiotropium, an inhaled long-acting muscarinic antagonist, on lung
      function were investigated in current smokers and nonsmokers with asthma treated
      with inhaled corticosteroids (ICSs) and other asthma controllers: inhaled long
      acting beta2 agonists, leukotriene receptor antagonists, and/or theophylline. We
      conducted a double-blind, placebo-controlled study of an inhaled single dose of
      tiotropium in 9 asthmatics currently smoking and 9 asthmatics who have never
      smoked in a crossover manner. Lung function was measured before and 1, 3, and 24
      h after inhalation of 18 MUg of tiotropium or a placebo. The primary outcome was
      a change in forced expiratory volume in 1 s (FEV1) from the baseline, and the
      secondary outcomes were changes in peak expiratory flow rate (PEFR), V50, and
      V25. At baseline, asthmatics with and without a smoking history had a mean FEV1
      of 2590 ml and 2220 ml and were taking a mean dose of ICSs of 1208 and 1000
      MUg/day, respectively. The increase from the baseline FEV1 was 169 ml and 105 ml
      higher at 3 h after tiotropium than after the placebo in current smokers and
      nonsmokers, respectively. PEFR, V50, and V25 were also significantly increased
      after tiotropium as compared with the placebo in both study groups. Changes in
      FEV1 and PEFR tended to be greater in asthmatics currently smoking than in
      subjects who have never smoked, although there were no statistical differences at
      any time points. Tiotropium resulted in improved lung function and symptoms both
      in current smoker and nonsmoker asthmatics. These findings suggest that
      tiotropium will provide a new strategy for the treatment of bronchial asthma.

PMID- 27888046
TI  - Proposed clinical guidance for excluding pregnancy prior to contraceptive
      initiation.

PMID- 27888047
TI  - Looking for a lost subdermal contraceptive implant? Think about the pulmonary
      artery.
AB  - This case highlights a rare but potentially life-threatening complication of a
      contraceptive implant insertion that was corrected by a noninvasive endovascular
      procedure. This procedure requires a quick intervention to be successful.

PMID- 27888048
TI  - Breaking the resistance of Escherichia coli: Antimicrobial activity of Berberis
      lycium Royle.
AB  - The antimicrobial activity of root bark of Berberis lycium and its principal
      component berberine was tested against a panel of microbial strains using agar
      well diffusion test and further analyzed using micro-broth dilution method.
      Preliminary analysis, on the basis of zone of Inhibition (ZOI) showed that the
      methanolic extract of B. lycium was highly effective against Escherichia coli
      (ZOI 41 +/- 1 mm). Among the bacterial strains E. coli was found to be most
      susceptible and among fungi Candida albicans was the most susceptible for
      berberine as well as the crude methanolic extract of the plant. Methanolic
      extract of the plant was more effective for E. coli (MIC 1.7 +/- 1.18; MBC 2.4 +/
      1.18) than berberine (MIC 3.5 +/- 0.57) (p < 0.05), whereas berberine was more
      effective than crude extracts for C. albicans. In addition, E. coli showed the
      development of resistant colonies after 72 h when tested with berberine but the
      development of such colonies was not observed with the methanolic extract of the
      plant. This could be due to the presence of resistance breaking molecules in the
      crude methanolic extract of B. lycium. Also the MIC index of crude methanolic
      extract was 1.39 for E. coli, which showed the mode of action to be bactericidal.
      HPLC analysis revealed the presence of berberine at highest concentration in
      methanolic extract of the plant, followed by aqueous extract. Potentiation of
      this berberine by resistance breaking molecules in the crude extract could be a
      possible explanation for its strong effectiveness.

PMID- 27888049
TI  - Complete overdentures retained by mini implants: A systematic review.
AB  - OBJECTIVE: The purpose of this systematic review was to evaluate the use of mini
      implants to retain complete overdentures in terms of survival rates of mini
      implants, marginal bone loss, satisfaction, and quality of life. DATA: This
      report followed the PRISMA Statement and PICO question. This review has been
      registered at PROSPERO under the number CRD42016036141. SOURCE: Two independent
      reviewers performed a comprehensive search of studies published until September
      2016 and listed in the PubMed/MEDLINE, Embase, and The Cochrane Library
      databases. The focused question was: is the use of mini implants feasible for
      prosthodontic rehabilitation with complete overdentures? RESULTS: The 24 studies
      selected for review evaluated 1273 patients whose mean age was 65.93 years; these
      patients had received 2494 mini implants and 386 standard implants for retaining
      overdenture prosthesis. The mean follow-up time was 2.48 years (range: 1-7
      years). There was a higher survival rate of mini implants (92.32%). More frequent
      failures for maxillary (31.71%) compared with mandibular arches (4.89%). The
      majority of studies revealed marginal bone loss values similar to those of
      standard implants (<1.5mm). All studies verified an increase in satisfaction and
      quality of life after rehabilitation treatment with mini dental implants.
      CONCLUSION: The present systematic review indicates that the use of mini implants
      for retaining overdenture prosthesis is considered an alternative treatment when
      standard treatment is not possible, since it presents high survival rates,
      acceptable marginal bone loss, and improvements in variables related to
      satisfaction and quality of life. CLINICAL SIGNIFICANCE: Based on the results of
      this study, the use of a minimum 4 and 6 mini implants can be considered a
      satisfactory treatment option for rehabilitation of the mandibular and maxillary
      arches respectively with a complete overdenture.

PMID- 27888050
TI  - Wake-Up Call: Pulmonary Arteriovenous Malformation.

PMID- 27888051
TI  - Absence of Oral Anticoagulation and Subsequent Outcomes Among Outpatients with
      Atrial Fibrillation.
AB  - BACKGROUND: Prior studies have shown a treatment gap in oral anticoagulation
      (OAC) use among patients with atrial fibrillation yet have incompletely
      characterized factors associated with failure to treat and subsequent outcomes in
      contemporary practice. METHODS: Using data collected between June 2010 and August
      2011 from 174 ambulatory care sites in the Outcomes Registry for Better Informed
      Treatment of Atrial Fibrillation, we identified factors associated with absence
      of OAC via stratified logistic regression. Using weighted Cox regression, we
      assessed the association between OAC non-use and subsequent outcomes over 2.5
      years. RESULTS: Among 9553 patients, 2202 (23.0%) were not on OAC. Among OAC
      nonrecipients, 1846 (83.8%) had a CHA2DS2-VASc score >=2. Factors independently
      associated with OAC non-use included atrial fibrillation type (paroxysmal odds
      ratio [OR] 0.73, 95% confidence interval [CI] 0.54-0.99; persistent OR 0.14, 95%
      CI 0.10-0.21; permanent OR 0.35, 95% CI 0.25-0.49; reference = new-onset), left
      atrial diameter enlargement (mild OR 0.80, 95% CI 0.66-0.97; moderate 0.58, 95%
      CI 0.47-0.73; severe 0.53, 95% CI 0.42-0.68; reference = normal diameter), and
      age >80 years (OR 1.04, 95% CI 1.02-1.08). Untreated patients had a higher risk
      of death (adjusted hazard ratio [HR] 1.22, 95% CI 1.05-1.41), a lower bleeding
      risk (adjusted HR 0.35, 95% CI 0.15-0.81), and a nonsignificant trend toward
      higher risk of stroke/non-central nervous system embolism/transient ischemic
      attack than those treated (adjusted HR 1.18, 95% CI 0.91-1.54). CONCLUSIONS: A
      majority of atrial fibrillation patients not treated with an OAC in current
      community practice meet guideline indications for treatment. Atrial fibrillation
      burden, chronicity, and comorbidity are associated with nontreatment. Untreated
      patients are at increased risk for adverse outcomes.

PMID- 27888052
TI  - Nonsteroidal Anti-Inflammatory Drugs and Clinical Outcomes in Patients Undergoing
      Coronary Artery Bypass Surgery.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in
      perioperative pain management of patients undergoing coronary artery bypass graft
      surgery. However, the association of periprocedural use of NSAIDs and clinical
      outcomes after coronary artery bypass graft is understudied. METHODS: We
      conducted a retrospective analysis using pooled data from 2 multicenter
      randomized controlled trials (PREVENT IV [n = 3014] and MEND-CABG II [n = 3023]).
      Rates of death, death or myocardial infarction, and death, myocardial infarction,
      or stroke in the 30 days following coronary artery bypass graft surgery were
      compared in patients using or not using perioperative NSAIDs. Inverse probability
      of treatment weighting and Cox proportional hazards regression models were used
      to adjust for confounding. RESULTS: A total of 5887 patients were studied. Median
      age was 65 years, 78% were male, and 91% were White. NSAIDs were used in 2368
      (40.2%) patients. The majority of patients (1822 [30.9%]) received NSAIDs after
      coronary artery bypass graft surgery; 289 (4.9%) used them prior to and after the
      surgery; and 257 (4.4) received NSAIDs prior to the surgery only. Adjusted 30-day
      outcomes were similar in patients receiving and not receiving NSAIDs (death:
      hazard ratio [HR] 1.18; 95% confidence interval [CI], 0.48-2.92; death or
      myocardial infarction: HR 0.87; 95% CI, 0.42-1.79; death, myocardial infarction,
      or stroke: HR 0.87; 95% CI, 0.46-1.65). CONCLUSION: In this pooled data analysis,
      perioperative NSAID use was common among patients undergoing coronary artery
      bypass graft surgery and was not associated with an increased short-term risk for
      major adverse clinical outcomes.

PMID- 27888053
TI  - Current Understanding of Atherogenesis.
AB  - Scientific understanding of atherogenesis is constantly developing. From
      Virchow's observations 160 years ago we now recognize the endothelial response to
      injury as inflammatory, involved in all stages of atherosclerosis. Endothelial
      activation may cause reversible injury or dysfunction, or lead to irreparable
      damage. Indeed, early atherosclerosis is reversible. The introduction of genome
      wide association testing has furthered the identification of potentially
      important genetic variants that help explain the heritability of coronary artery
      disease as well as spontaneous cases of severe coronary artery disease in
      patients with otherwise minimal risk factors. However, the mechanisms by which
      many of the newer variants exert their influence remain unknown.

PMID- 27888054
TI  - A Red Herring in the Green Grass: Syphilitic Membranous Glomerulonephritis.

PMID- 27888055
TI  - Dietary choline levels modify the effects of prenatal alcohol exposure in rats.
AB  - Prenatal alcohol exposure can cause a range of physical and behavioral
      alterations; however, the outcome among children exposed to alcohol during
      pregnancy varies widely. Some of this variation may be due to nutritional
      factors. Indeed, higher rates of fetal alcohol spectrum disorders (FASD) are
      observed in countries where malnutrition is prevalent. Epidemiological studies
      have shown that many pregnant women throughout the world may not be consuming
      adequate levels of choline, an essential nutrient critical for brain development,
      and a methyl donor. In this study, we examined the influence of dietary choline
      deficiency on the severity of fetal alcohol effects. Pregnant Sprague-Dawley rats
      were randomly assigned to receive diets containing 40, 70, or 100% recommended
      choline levels. A group from each diet condition was exposed to ethanol
      (6.0g/kg/day) from gestational day 5 to 20 via intubation. Pair-fed and ad lib
      lab chow control groups were also included. Physical and behavioral development
      was measured in the offspring. Prenatal alcohol exposure delayed motor
      development, and 40% choline altered performance on the cliff avoidance task,
      independent of one another. However, the combination of low choline and prenatal
      alcohol produced the most severe impairments in development. Subjects exposed to
      ethanol and fed the 40% choline diet exhibited delayed eye openings,
      significantly fewer successes in hindlimb coordination, and were significantly
      overactive compared to all other groups. These data suggest that suboptimal
      intake of a single nutrient can exacerbate some of ethanol's teratogenic effects,
      a finding with important implications for the prevention of FASD.

PMID- 27888056
TI  - Sclerostin expression and functions beyond the osteocyte.
AB  - Sclerostin, the product of the SOST gene, is a secreted inhibitor of Wnt
      signaling that is produced by osteocytes to regulate bone formation. While it is
      often considered an osteocyte-specific protein, SOST expression has been reported
      in numerous other cell types, including hypertrophic chondrocytes and
      cementocytes. Of interest, SOST/sclerostin expression is altered in certain
      pathogenic conditions, including osteoarthritis and rheumatic joint disease, and
      it is unclear whether sclerostin plays a protective role or whether sclerostin
      may mediate disease pathogenesis. Therefore, as anti-sclerostin antibodies are
      being developed for the treatment of osteoporosis, it is important to understand
      the functions of sclerostin beyond the regulation of bone formation.

PMID- 27888057
TI  - Association between rs2294020 in X-linked CCDC22 and susceptibility to autoimmune
      diseases with focus on systemic lupus erythematosus.
AB  - Autoimmune diseases often share common susceptibility genes. Most genetic
      variants associated with susceptibility to systemic lupus erythematosus are also
      associated with other autoimmune diseases. The X-linked variant rs2294020 is
      positioned in exon 7 of the CCDC22 gene. The encoded protein functions in the
      regulation of NF-kappaB, a master regulator in immune response. The aim of this
      study is to investigate whether the rs2294020 polymorphism may be a general
      susceptibility factor for autoimmunity. We evaluated case-control association
      between the occurrence of rs2294020 and different autoimmune diseases, including
      new data for systemic lupus erythematosus and previous genome-wide association
      studies (GWAS) (though most did not analyse the X chromosome) of psoriasis,
      celiac disease, Crohn's disease, ulcerative colitis, multiple sclerosis,
      vitiligo, type-1 diabetes, rheumatoid arthritis, and ankylosing spondylitis.
      Cases from patients affected by amyotrophic lateral sclerosis and type-2 diabetes
      were also included in the study. We detected nominal significant associations of
      rs2294020 with systemic lupus erythematosus (additive model test: p=0.01),
      vitiligo (p=0.016), psoriasis (p=0.038), and in only one of two studies of
      multiple sclerosis (p=0.03). Our results suggest that rs2294020 is associated
      with the risk of several autoimmune diseases in European populations,
      specifically with diseases that present themselves, among else, in the skin.

PMID- 27888058
TI  - Cerebrovascular reactivity mapping without gas challenges.
AB  - Cerebrovascular reactivity (CVR), the ability of cerebral vessels to dilate or
      constrict, has been shown to provide valuable information in the diagnosis and
      treatment evaluation of patients with various cerebrovascular conditions. CVR
      mapping is typically performed using hypercapnic gas inhalation as a vasoactive
      challenge while collecting BOLD images, but the inherent need of gas inhalation
      and the associated apparatus setup present a practical obstacle in applying it in
      routine clinical use. Therefore, we aimed to develop a new method to map CVR
      using resting-state BOLD data without the need of gas inhalation. This approach
      exploits the natural variation in respiration and measures its influence on BOLD
      MRI signal. In this work, we first identified a surrogate of the arterial CO2
      fluctuation during spontaneous breathing from the global BOLD signal. Second, we
      tested the feasibility and reproducibility of the proposed approach to use the
      above-mentioned surrogate as a regressor to estimate voxel-wise CVR. Third, we
      validated the "resting-state CVR map" with a conventional CVR map obtained with
      hypercapnic gas inhalation in healthy volunteers. Finally, we tested the utility
      of this new approach in detecting abnormal CVR in a group of patients with
      Moyamoya disease, and again validated the results using the conventional gas
      inhalation method. Our results showed that global BOLD signal fluctuation in the
      frequency range of 0.02-0.04Hz contains the most prominent contribution from
      natural variation in arterial CO2. The CVR map calculated using this signal as a
      regressor is reproducible across runs (ICC=0.91+/-0.06), and manifests a strong
      spatial correlation with results measured with a conventional hypercapnia-based
      method in healthy subjects (r=0.88, p<0.001). We also found that resting-state
      CVR was able to identify vasodilatory deficit in patients with steno-occlusive
      disease, the spatial pattern of which matches that obtained using the
      conventional gas method (r=0.71+/-0.18). These results suggest that CVR obtained
      with resting-state BOLD may be a useful alternative in detecting vascular
      deficits in clinical applications when gas challenge is not feasible.

PMID- 27888060
TI  - Faith and oscillations recovered: On analyzing EEG/MEG signals during tACS.
AB  - Despite recent success in analyzing brain oscillations recorded during
      transcranial alternating current stimulation (tACS), the field still requires
      further research to establish standards in artifact removal methods. This
      includes taking a step back from the removal of the tACS artifact and thoroughly
      characterizing the to-be-removed artifact. A recent study by Noury et al. (2016)
      contributed importantly to this endeavour by showing the existence of nonlinear
      artefacts in the tACS signal as seen by MEG and EEG. Unfortunately however this
      paper conveys the message that current artifact removal attempts have failed
      altogether and that-based on these available tools-brain oscillations recorded
      during tACS cannot be analyzed using MEG and EEG. Here we want to balance this
      overly pessimistic conclusion: In-depth reanalyses of our own data and phantom
      head measurements indicate that nonlinearities can occur, but only when technical
      limits of the stimulator are reached. As such they are part of the "real"
      stimulation and not a specific MEG analysis problem. Future tACS studies should
      consider these technical limits to avoid any nonlinear modulations of the tACS
      artifact. We conclude that even with current approaches, brain oscillations
      recorded during tACS can be meaningfully studied in many practical cases.

PMID- 27888059
TI  - Towards a consensus regarding global signal regression for resting state
      functional connectivity MRI.
AB  - The number of resting state functional connectivity MRI studies continues to
      expand at a rapid rate along with the options for data processing. Of the
      processing options, few have generated as much controversy as global signal
      regression and the subsequent observation of negative correlations (anti
      correlations). This debate has motivated new processing strategies and
      advancement in the field, but has also generated significant confusion and
      contradictory guidelines. In this article, we work towards a consensus regarding
      global signal regression. We highlight several points of agreement including the
      fact that there is not a single "right" way to process resting state data that
      reveals the "true" nature of the brain. Although further work is needed,
      different processing approaches likely reveal complementary insights about the
      brain's functional organisation.

PMID- 27888061
TI  - Secretory function of ovarian cells and myometrial contractions in cow are
      affected by chlorinated insecticides (chlordane, heptachlor, mirex) in vitro.
AB  - The aim of the study was to investigate the effect of chlordane, heptachlor and
      mirex, on hormonal regulation of the force of myometrial contractions.
      Myometrial, endometrial, granulosa and luteal cells as well as strips of
      myometrium from non-pregnant cows were incubated with three insecticides at
      environmentally relevant doses (0.1, 1 or 10ng/ml). None of the insecticides
      affected the viability of studied cells. Chlordane stimulated, while heptachlor
      and mirex inhibited, secretion of testosterone and estradiol from granulosa cells
      as well as secretion of progesterone from luteal cells, respectively. Secretion
      of oxytocin (OT) from granulosa cells was increased after incubation with all
      studied insecticides. Only mirex stimulated OT secretion from luteal cells, while
      heptachlor inhibited this effect. None of them affected synthesis of OT in luteal
      cells and prostaglandins (PGF2 and PGE2) secretion from uterine cells, except
      PGE2 secretion from endometrial cells was decreased when the cells were incubated
      with 0.1ng/ml of chlordane. Basal and OT-stimulated myometrial contractions were
      increased by mirex and decreased by heptachlor. The data show that the
      insecticides altered secretory function of ovarian cells. Heptachlor and mirex
      affected also myometrial contractions in vitro, but uterine secretion of
      prostaglandins were not involved in the mechanism of that adverse effect of
      insecticides. The data indicate on potential of these insecticides to disturb
      fertilisation, blastocyst implantation or even the length of gestation.

PMID- 27888062
TI  - Neurotrophin biology at NGF 2016: From fundamental science to clinical
      applications.

PMID- 27888063
TI  - Notch1 signalling inhibits apoptosis of human dental follicle stem cells via both
      the cytoplasmic mitochondrial pathway and nuclear transcription regulation.
AB  - Dental follicle stem cells (DFSCs) have been considered as promising candidate
      cells for periodontal tissue regeneration. Understanding the signalling pathways
      underlying the apoptosis of DFSCs will facilitate its biomedical application.
      Here we showed that Notch1 signalling could inhibit DFSCs apoptosis because the
      constitutive overexpression of the intracellular domain of Notch1 (ICN1) promoted
      proliferation and suppressed apoptosis by inhibiting cytoplasmic mitochondrial
      membrane depolarization, cytochrome c release and activation of caspase-9 and
      caspase-3. The survival-promoting effect of Notch1 was also accomplished by up
      regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1, down-regulation of the
      pro-apoptotic proteins Bax and Bad, and blockade of Bax multimerization.
      Moreover, p-Akt (S473) was significantly increased after ectopic Notch 1
      activation. The expression of p53 was also inhibited in Notch1-overexpressing
      DFSCs, while the ectopic expression of p53 promoted apoptosis even when Notch1
      was overexpressed. Meanwhile, all of the opposite phenomena were observed in
      Notch1 shRNA-silenced DFSCs. Our data strongly suggested that Notch1 signalling
      inhibited the apoptosis of DFSCs via the cytoplasmic mitochondrial pathway and
      ICN-Akt signalling pathway, together with nuclear gene expression regulation.
      These findings would provide molecular cues for the further medical application
      of DFSCs.

PMID- 27888064
TI  - Molecular cloning and nutrient regulation analysis of long chain acyl-CoA
      synthetase 1 gene in grass carp, Ctenopharyngodon idella L.
AB  - Long chain acyl-CoA synthetase 1 (ACSL1), a key regulatory enzyme of fatty acid
      metabolism, catalyzes the conversion of long-chain fatty acids to acyl-coenzyme
      A. The full-length cDNAs of ACSL1a and ACSL1b were cloned from the liver of a
      grass carp. Both cDNAs contained a 2094bp open reading frame encoding 697 amino
      acids. Amino acid sequence alignment showed that ACSL1a shared 73.5% sequence
      identity with ACSL1b. Each of the two ACSL1s proteins had a transmembrane domain,
      a P-loop domain, and L-, A-, and G-motifs, which were relatively conserved in
      comparison to other vertebrates. Relative expression profile of ACSL1 mRNAs in
      different tissues indicated that ACSL1a is highly expressed in heart, mesenteric
      adipose, and brain tissues, whereas ACSL1b is highly expressed in heart, white
      muscle, foregut, and liver tissues. Nutrient regulation research showed that the
      expression levels of ACSL1a and ACSL1b were significantly down-regulated when 3,
      6, and 9% fish oil were added in diet of grass carp as compared to the control
      group. However, no significant difference in the levels of ACSL1 mRNA was
      observed between the experimental groups. This study demonstrated the
      relationship between ACSL1a and ACSL1b genes in grass carp and laid a foundation
      for further research on ACSL family members in other species.

PMID- 27888065
TI  - Comparing the effects of sustained and transient spatial attention on the
      orienting towards and the processing of electrical nociceptive stimuli.
AB  - We examined whether sustained vs. transient spatial attention differentially
      affect the processing of electrical nociceptive stimuli. Cued nociceptive stimuli
      of a relevant intensity (low or high) on the left or right forearm required a
      foot pedal press. The cued side varied trial wise in the transient attention
      condition, while it remained constant during a series of trials in the sustained
      attention condition. The orienting phase preceding the nociceptive stimuli was
      examined by focusing on lateralized EEG activity. ERPs were computed to examine
      the influence of spatial attention on the processing of the nociceptive stimuli.
      Results for the orienting phase showed increased ipsilateral alpha and beta power
      above somatosensory areas in both the transient and the sustained attention
      conditions, which may reflect inhibition of ipsilateral and/or disinhibition of
      contralateral somatosensory areas. Cued nociceptive stimuli evoked a larger N130
      than uncued stimuli, both in the transient and the sustained attention
      conditions. Support for increased efficiency of spatial attention in the
      sustained attention condition was obtained for the N180 and the P540 component.
      We concluded that spatial attention is more efficient in the case of sustained
      than in the case of transient spatial attention.

PMID- 27888066
TI  - Looking Back at Baltimore 1997.

PMID- 27888067
TI  - Allele and genotype frequencies of polymorphisms in cytokine genes in ethnic
      Russian individuals from Moscow, Russia.
AB  - Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were
      genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G
      634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6G-174C
      and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were
      determined using real-time polymerase chain reaction with TaqMan probes and
      polymerase chain reaction followed by melting analysis of dual-labeled probe.
      Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all
      studied polymorphisms. Genotype data are available in the Allele Frequencies Net
      Database under identifier AFND 3367 and the population name "Russia Moscow
      Cytokine".

PMID- 27888068
TI  - Associations of single nucleotide polymorphisms of PTPN22 and Ctla4 genes with
      the risk of allergic rhinitis in a Chinese Han population.
AB  - BACKGROUND: Allergic rhinitis (AR) is an inflammatory disorder of the upper
      airway. Protein tyrosine phosphatase non-receptor 22 encoded by PTPN22 gene and
      cytotoxic T-lymphocyte associated 4 encoded by Ctla4 gene are associated with
      autoimmune diseases. PURPOSE: This study was performed to evaluate the potential
      association of PTPN22 and Ctla4 single nucleotide polymorphisms (SNPs) with AR in
      a Chinese Han population. METHODS: A case-control study was performed in 783
      Chinese AR patients and 811 healthy controls. Three SNPs in PTPN22 gene
      (rs2488457, rs1310182, and rs3789604) and 6 SNPs in Ctla4 gene (rs3087243,
      rs231779, rs11571302, rs11571315, rs231725, and rs35219727) were detected using a
      polymerase chain reaction-restriction fragment length polymorphism assay (PCR
      RFLP). RESULTS: For PTPN22 gene, a significantly decreased prevalence of the
      rs2488457 CC genotype and C allele was found in AR patients. The frequencies of
      the rs1310182 CC genotype, CT genotype, and C allele were significantly
      associated with the risk of AR. For Ctla4 gene, a significantly increased
      prevalence of the rs11571302 AA genotype, CA genotype and A allele was noted in
      AR patients. CONCLUSION: SNPs of PTPN22 and Ctla4 genes are significantly
      associated with the risk of AR in the Chinese Han population.

PMID- 27888069
TI  - Vertebrate embryos as tools for anti-angiogenic drug screening and function.
AB  - The development of new angiogenic inhibitors highlights a need for robust
      screening assays that adequately capture the complexity of vessel formation, and
      allow for the quantitative evaluation of the teratogenicity of new anti
      angiogenic agents. This review discusses the use of screening assays in
      vertebrate embryos, specifically focusing upon chicken and zebrafish embryos, for
      the detection of anti-angiogenic agents.

PMID- 27888070
TI  - Phosphoramide mustard induces autophagy markers and mTOR inhibition prevents
      follicle loss due to phosphoramide mustard exposure.
AB  - Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide.
      Postnatal day 4 Fisher 344 rat ovaries were exposed to vehicle control (1% DMSO)
      or PM (60MUM)+/-LY294002 or rapamycin for 2 or 4 d. Transmission election
      microscopy revealed abnormally large golgi apparatus and electron dense
      mitochondria in PM-exposed ovaries prior to and at the time of follicle
      depletion. PM exposure increased (P<0.05) mRNA abundance of Bbc3, Cdkn1a, Ctfr,
      Edn1, Gstp1, Nqo1, Tlr4, Tnfrsfla, Txnrd1 and decreased (P<0.05) Casp1 and Il1b
      after 4d. PM exposure increased (P<0.1) BECN1 and LAMP, decreased (P<0.1) ABCB1
      and did not alter ABCC1 protein. LY294002 did not impact PM-induced ovotoxicity,
      but decreased ABCC1 and ABCB1 protein. Rapamycin prevented PM-induced follicle
      loss. These data suggest that the mammalian target of rapamycin, mTOR, may be a
      gatekeeper of PM-induced follicle loss.

PMID- 27888071
TI  - Cell type-specific expression of FoxP2 in the ferret and mouse retina.
AB  - Although the anatomical and physiological properties of subtypes of retinal
      ganglion cells (RGCs) have been extensively investigated, their molecular
      properties are still unclear. Here, we examined the expression patterns of FoxP2
      in the retina of ferrets and mice. We found that FoxP2 was expressed in small
      subsets of neurons in the adult ferret retina. FoxP2-positive neurons in the
      ganglion cell layer were divided into two groups. Large FoxP2-positive neurons
      expressed Brn3a and were retrogradely labeled with cholera toxin subunit B
      injected into the optic nerve, indicating that they are RGCs. The soma size and
      the projection pattern of FoxP2-positive RGCs were consistent with those of X
      cells. Because we previously reported that FoxP2 was selectively expressed in X
      cells in the ferret lateral geniculate nucleus (LGN), our findings indicate that
      FoxP2 is specifically expressed in the parvocellular pathway from the retina to
      the LGN. Small FoxP2-positive neurons were positive for GAD65/67, suggesting that
      they are GABAergic amacrine cells. Most Foxp2-positive cells were RGCs in the
      adult mouse retina. Dendritic morphological analyses suggested that Foxp2
      positive RGCs included direction-selective RGCs in mice. Thus, our findings
      suggest that FoxP2 is expressed in specific subtypes of RGCs in the retina of
      ferrets and mice.

PMID- 27888072
TI  - Movement-related cortical magnetic fields associated with self-paced tongue
      protrusion in humans.
AB  - Sophisticated tongue movements are coordinated finely via cortical control. We
      elucidated the cortical processes associated with voluntary tongue movement.
      Movement-related cortical fields were investigated during self-paced repetitive
      tongue protrusion. Surface tongue electromyograms were recorded to determine
      movement onset. To identify the location of the primary somatosensory cortex
      (S1), tongue somatosensory evoked fields were measured. The readiness fields
      (RFs) over both hemispheres began prior to movement onset and culminated in the
      motor fields (MFs) around movement onset. These signals were followed by
      transient movement evoked fields (MEFs) after movement onset. The MF and MEF peak
      latencies and magnitudes were not different between the hemispheres. The MF
      current sources were located in the precentral gyrus, suggesting they were
      located in the primary motor cortex (M1); this was contrary to the MEF sources,
      which were located in S1. We conclude that the RFs and MFs mainly reflect the
      cortical processes for the preparation and execution of tongue movement in the
      bilateral M1, without hemispheric dominance. Moreover, the MEFs may represent
      proprioceptive feedback from the tongue to bilateral S1. Such cortical processing
      related to the efferent and afferent information may aid in the coordination of
      sophisticated tongue movements.

PMID- 27888073
TI  - Early-life inflammation with LPS delays fear extinction in adult rodents.
AB  - A large body of evidence has been brought forward connecting developmental immune
      activation to abnormal fear and anxiety levels. Anxiety disorders have extremely
      high lifetime prevalence, yet susceptibility factors that contribute to their
      emergence are poorly understood. In this research we investigated whether an
      inflammatory insult early in life can alter the response to fear conditioning in
      adulthood. Fear learning and extinction are important and adaptive behaviors,
      mediated largely by the amygdala and its interconnectivity with cortico-limbic
      circuits. Male and female rat pups were given LPS (100MUg/kg i.p.) or saline at
      postnatal day 14; LPS activated cFos expression in the central amygdala 2.5h
      after exposure, but not the basal or lateral nuclei. When tested in adulthood,
      acquisition of an auditory cued or contextual learned fear memory was largely
      unaffected as was the extinction of fear to a conditioned context. However, we
      detected a deficit in auditory fear extinction in male and female rats that
      experienced early-life inflammation, such that there is a significant delay in
      fear extinction processes resulting in more sustained fear behaviors in response
      to a conditioned cue. This response was specific to extinction training and did
      not persist into extinction recall. The effect could not be explained by
      differences in pain threshold (unaltered) or in baseline anxiety, which was
      elevated in adolescent females only and unaltered in adolescent males and adult
      males and females. This research provides further evidence for the involvement of
      the immune system during development in the shaping of fear and anxiety related
      behaviors.

PMID- 27888074
TI  - Toxoplasma gondii immune mapped protein 1 is anchored to the inner leaflet of the
      plasma membrane and adopts a novel protein fold.
AB  - The immune mapped protein 1 (IMP1) was first identified as a protective antigen
      in Eimeria maxima and described as vaccine candidate and invasion factor in
      Toxoplasma gondii. We show here that TgIMP1 localizes to the inner leaflet of
      plasma membrane (PM) via dual acylation. Mutations either in the N-terminal
      myristoylation or palmitoylation sites (G2 and C5) cause relocalization of TgIMP1
      to the cytosol. The first 11 amino acids are sufficient for PM targeting and the
      presence of lysine (K7) is critical. Disruption of TgIMP1 gene by double
      homologous recombination revealed no invasion defect or any measurable alteration
      in the lytic cycle of tachyzoites. Following immunization with TgIMP1 DNA
      vaccine, mice challenged with either wild type or IMP1-ko parasites showed no
      significant difference in protection. The sequence analysis identified a
      structured C-terminal domain that is present in a broader family of IMP1-like
      proteins conserved across the members of Apicomplexa. We present the solution
      structure of this domain determined from NMR data and describe a new protein fold
      not seen before.

PMID- 27888075
TI  - The domain II loops of Bacillus thuringiensis Cry1Aa form an overlapping
      interaction site for two Bombyx mori larvae functional receptors, ABC transporter
      C2 and cadherin-like receptor.
AB  - Information about the receptor-interaction region of Cry toxins, insecticidal
      proteins produced by Bacillus thuringiensis, is needed to elucidate the mode of
      action of Cry toxins and improve their toxicity through protein engineering. We
      analyzed the interaction sites on Cry1Aa with ABC transporter C2 (ABCC2), one of
      the most important Cry1A toxin receptors. A competitive binding assay revealed
      that the Bombyx mori ABCC2 (BmABCC2) Cry1A binding site was the same as the
      BtR175 binding site, suggesting that the loop region of Cry1Aa domain II is a
      binding site. Next, we constructed several domain II loop mutant toxins and
      tested their binding affinity in an SPR analysis, and also performed a cell
      swelling assay to evaluate receptor-mediated cytotoxicity. Our results indicate
      that the loop regions required for BtR175 and BmABCC2 binding and the regions
      important for cytotoxicity partially overlap. Our results also suggest that
      receptor binding is necessary but not sufficient for cytotoxicity. This is the
      first report showing the region of interaction between ABCC2 and Cry1Aa and the
      cytotoxicity-relevant properties of the Cry1Aa domain II loop region.

PMID- 27888076
TI  - Proteome-wide identification of lysine succinylation in thermophilic and
      mesophilic bacteria.
AB  - Lysine succinylation, one of post-translational acylations conserved from
      eukaryotes to bacteria, plays regulatory roles in various cellular processes.
      However, much remains unknown about the general and specific characteristics of
      lysine succinylation among bacteria, and about its functions different from those
      of other acylations. In this study, we characterized lysine succinylation, a
      newly discovered widespread type of lysine acylation in five bacterial species
      with different characteristics such as optimal growth temperature and cell wall
      structure. This study is the first to demonstrate that succinylation is general
      phenomenon occurring not only in mesophiles but also in thermophiles. Mapping of
      succinylation sites on protein structures revealed that succinylation occurs at
      many lysine residues important for protein function. Comparison of the
      succinylation sites in the five bacterial species provides insights regarding
      common protein regulation mechanisms utilizing lysine succinylation. Many
      succinylation sites were conserved among five bacteria, especially between
      Geobacillus kaustophilus and Bacillus subtilis, some of which are functionally
      important sites. Furthermore, systematic comparison of the succinyl-proteome
      results and our previous propionyl-proteome results showed that the abundance of
      these two types of acylations is considerably different among the five bacteria
      investigated. Many succinylation and propionylation events were detected in G.
      kaustophilus, whereas Escherichia coli and B. subtilis exhibited high
      succinylation and low propionylation; low succinylation and high propionylation
      were identified in Thermus thermophilus, and low succinylation and propionylation
      were observed in Rhodothermus marinus. Comparison of the characteristics of
      lysine succinylation and lysine propionylation suggested these two types of
      acylation play different roles in cellular processes.

PMID- 27888077
TI  - Subcortical Low-Intensity Lesions on Fluid-Attenuated Inversion Recovery Images
      After Revascularization Surgery for Moyamoya Disease.
AB  - OBJECTIVE: Although uncommon, subcortical low-intensity (SCLI) changes on fluid
      attenuated inversion recovery images are observed in various diseases, including
      cerebral ischemia. Here, we aimed to clarify the incidence and clinical
      implications of SCLI changes after revascularization surgery for moyamoya
      disease, focusing on the correlation with postoperative transient neurologic
      events (TNEs). METHODS: In this retrospective case series analysis, we included
      10 hemispheres from 9 adults with moyamoya disease who underwent
      revascularization surgery. Subcortical signal intensity at the 5 gyri around the
      anastomosis point was quantitatively measured at 1 week and 3 months
      postoperatively. Changes in cerebral blood flow (CBF) were assessed using single
      photon emission computed tomography. RESULTS: Images taken 1 week after surgery
      showed widespread SCLI changes below the operative fields in all 10 cases, but
      these changes normalized by 3 months. In addition, the changes in signal
      intensity at anastomoses negatively correlated with the changes in CBF (R2 =
      0.36; P = 0.039). Postoperative TNEs occurred in 6 cases (60%) but were resolved
      within 17 days after surgery. Postoperative CBF increased in 9 of the 10 cases,
      with a median of 23%; however, these increases were not associated with the
      development of TNEs. The SCLI changes at the anastomosis points did not differ by
      the experience of TNEs. CONCLUSIONS: Early after surgery, SCLI changes are common
      findings below the operative fields but negatively correlate with increases in
      CBF. Although no significant association was found between TNEs and the SCLI
      changes, the synchronized development of these phenomena may suggest a common
      underlying pathogenesis.

PMID- 27888078
TI  - Basilar Artery Herniation into the Sphenoid Sinus Secondary to Traumatic Skull
      Base Fractures: Case Report and Review of the Literature.
AB  - BACKGROUND: Traumatic clival fractures occur with less than 0.6% frequency and
      can be associated with significant neurovascular injuries. The most serious of
      these injuries is to the basilar artery in which the artery is dissected or is
      fully occluded, resulting in infarction of the brainstem and cerebellum. Among
      early reports of these injuries, postmortem autopsy showed entrapment, or
      incarceration, of the basilar artery at the clival fracture site. A literature
      search revealed 11 cases of entrapment of the basilar artery within a clival
      fracture. CASE DESCRIPTION: This report describes a 59-year-old man after a motor
      vehicle crash with computed tomography showing a basilar artery herniation
      through a sphenoid sinus fracture. The patient subsequently developed brainstem
      and cerebellar infarcts. CONCLUSIONS: Basilar artery incarceration and herniation
      through the sphenoid sinus is rare. Such an injury portends a poor prognosis. We
      discuss the relevant clinical imaging and review the literature.

PMID- 27888079
TI  - Neglected Recurrent Scalp Sinus: Calvarial Tuberculosis with Intracranial and
      Extracranial Extension.
AB  - BACKGROUND: Calvarial tuberculosis (TB) with intracranial tuberculoma and skin
      involvement is rare condition even in endemic regions. CASE PRESENTATION: A 43
      year-old man presented with a generalized seizure, altered mental state, scalp
      swelling, and pus-discharging sinus over the scalp. Magnetic resonance imaging of
      the brain indicated a conflicting diagnosis of anaplastic meningiomas and chronic
      osteomyelitis with intracranial extension. Debridement and drainage of
      intracranial pus was performed. Histopathologic examination revealed TB. After
      surgery, the patient's general condition improved, and he was started on
      antitubercular drugs. CONCLUSIONS: Calvarial TB manifests with various clinical
      features, and strong clinical suspicion is needed to diagnose and treat it. Only
      a few cases of calvarial TB with either skin involvement or intracranial
      extension have been reported in the literature. The present case was challenging
      to diagnose with a rare presentation involving both intracranial and extracranial
      extension.

PMID- 27888080
TI  - Comparison of Consecutive, Interval, and Skipped Pedicle Screw Techniques in
      Moderate Lenke Type 1 Adolescent Idiopathic Scoliosis.
AB  - OBJECTIVE: To compare perioperative, radiographic, and Scoliosis Research Society
      22 (SRS-22) outcomes of consecutive, interval, and skipped pedicle screw
      techniques in patients with moderate Lenke type 1 adolescent idiopathic scoliosis
      (AIS). METHODS: We retrospectively reviewed 65 consecutive moderate Lenke type 1
      AIS patients at a single institution using all-pedicle screw constructs, with a
      minimum of 2 years of follow-up. In the consecutive group (C group, n = 22),
      pedicle screws were instrumented at consecutive levels bilaterally. In the
      interval group (I group, n = 18), pedicle screws were placed at every level on
      the concave side while skipping levels on the convex side. In the skipped group
      (S group, n = 25), pedicle screws were instrumented by skipping levels
      bilaterally. Perioperative, radiographic, and SRS-22 measurements were analyzed
      with a 1-way analysis of variance. RESULTS: No significant differences were found
      in length of hospital stay, fused levels, coronal correction, and SRS-22 scores
      among the 3 groups. Increased surgery time was found in the C group compared with
      the I and S groups (P = 0.001 and P = 0.005, respectively). Decreased blood loss
      and blood transfusions were found in the S group compared with the C group (P =
      0.04 and P = 0.047, respectively). Decreased implant costs were found in the S
      group compared with the C and I groups (P < 0.001 and P = 0.03, respectively).
      CONCLUSIONS: Consecutive, interval, and skipped pedicle screw techniques all
      provide satisfactory deformity correction and SRS-22 outcomes with few
      complications. With better perioperative outcomes, interval and skipped pedicle
      screw techniques are the more cost-effective options for patients with moderate
      Lenke type 1 AIS.

PMID- 27888081
TI  - Bow Hunter's Syndrome from a Tortuous V1 Segment Vertebral Artery Treated with
      Stent Placement.
AB  - BACKGROUND: Bow hunter's syndrome is a dynamic and reversible occlusion of the
      vertebral artery occurring after rotation or extension of the neck. The V3
      segment is the most common site of compression, especially at the atlantoaxial
      joint. Surgical decompression with or without cervical fusion has been the
      mainstay of therapy. Endovascular intervention, such as placement of stents, is
      rarely performed. METHODS: We report a patient with bow hunter's syndrome from
      tortuosity of the V1 segment of the VA treated with a self-expanding biliary
      stent placement. RESULTS: The symptoms where completely resolved by this
      treatment. CONCLUSIONS: Stent placement is a safe and effective option for V1
      segment causes of Bow Hunter's syndrome, especially in absence of bony
      compression.

PMID- 27888082
TI  - Bifurcation Location Is Significantly Associated with Rupture of Small
      Intracranial Aneurysms (<5 mm).
AB  - BACKGROUND AND OBJECTIVE: Patients with small (<5 mm) unruptured intracranial
      aneurysms (UIAs) are at risk of subarachnoid hemorrhage, but risk assessment of
      these patients remains controversial in daily clinical practice. We aimed to
      identify the risk factors of aneurysmal rupture in these patients. METHODS: We
      retrospectively analyzed consecutive patients with small UIAs who were admitted
      to our center between February 2009 and December 2014. The enrolled patients were
      divided into ruptured and unruptured groups. The risk factors for aneurysmal
      rupture were determined using multivariate logistic regression analysis. RESULTS:
      A total of 548 patients with 618 small intracranial aneurysms (267 ruptured and
      351 unruptured) were included. Univariate analysis showed that rupture of small
      aneurysms was related to sex, age, smoking, hypertension, aspect ratio, size
      ratio, irregular shape, aneurysm width, height, and neck diameter, and location
      at bifurcation or posterior circulation. Multivariate logistic regression showed
      that rupture was associated with bifurcation location (odds ratio [OR], 5.409;
      95% confidence interval [CI], 3.656-8.001; P < 0.001), size ratio (OR, 3.092; 95%
      CI, 2.002-4.774; P < 0.001), location (OR, 2.624; 95% CI, 1.428-4.824; P =
      0.002), hypertension (OR, 1.698; 95% CI, 1.1140-2.527; P = 0.009), and age at
      diagnosis of UIA (OR, 1.826; 95% CI, 1.225-2.723; P = 0.003). CONCLUSIONS: This
      study showed that 70.4% of small ruptured intracranial aneurysms (<5 mm) were
      located at parent artery bifurcations and that bifurcation location was a
      significant independent factor for the risk of rupture of small UIAs (<5 mm).
      Prophylactic treatment should be recommended for small UIAs in this location.

PMID- 27888083
TI  - Clinical and Imaging Evaluation of Transuncus Selective Amygdalohippocampectomy.
AB  - BACKGROUND: Various reports have described the transuncus (TU) approach as a
      selective route to the amygdala and hippocampus, but this approach has not yet
      been submitted to solid postoperative imaging analysis. The objective of this
      study was to evaluate the anatomy, surgical technique, postoperative imaging
      analysis, and outcome in a series of patients with temporal lobe epilepsy who
      underwent selective amigdalohippocampectomy via a TU approach. METHODS: This was
      a prospective study of 25 consecutive patients who underwent selective
      amigdalohippocampectomy through a TU approach. The temporal stem and temporal
      pole were evaluated through different modalities of 3-Tesla magnetic resonance
      imaging, including tractography of optic radiation (OR), uncinate fascicle, and
      inferior fronto-occipital fascicle. Visual field analysis was performed with
      automated perimetry. RESULTS: The mean age was 40 +/- 8.21 years, and mean follow
      up was 26.44 + 12.58 months. Postoperatively, 21 patients (84%) were classified
      as Engel I (good seizure control). Diffusion tensor imaging (DTI) data showed
      that 78.2% of patients had some structural damage to the temporal stem and fibers
      of the uncinate fascicle were identified postoperatively in only 3 patients
      (13.04%). The inferior fronto-occipital fascicle was identified in 18 patients
      (78.3%); however, subsequent DTI analysis of the remaining fibers showed them to
      be damaged. Integrity of the OR did not differ between these 2 groups.
      CONCLUSIONS: A TU approach is a feasible and efficient approach to selective
      amigdalohippocampectomy for surgical treatment of temporal lobe epilepsy.
      Postoperative DTI analysis suggests that a TU approach results in more injury to
      the temporal stem and its associated white matter fiber tracts than expected by
      previous anatomic studies; however, it was efficient in preserving OR.

PMID- 27888084
TI  - Are Locked Facets a Contraindication for Extreme Lateral Interbody Fusion?
AB  - BACKGROUND: Extreme lateral interbody fusion (ELIF) has gained popularity as a
      minimally invasive treatment allowing for indirect decompression of neural
      elements. However, evidence regarding the influence of facet degeneration (FD)
      and facet tropism (FT) toward indirect decompression is lacking. The aim of the
      study was to evaluate whether indirect decompression is impaired by FD and FT in
      patients undergoing ELIF. METHODS: Thirty-seven patients undergoing ELIF were
      included in a retrospective study. Radiographic parameters including disk height,
      segmental disk angle, foraminal area, FD, FT, and clinical outcome parameters
      (Oswestry Disability Index and Visual Analog Scale) were measured preoperatively
      and postoperatively. FD and FT were correlated with radiographic and clinical
      outcome parameters in order to determine predictors restricting indirect
      decompression. RESULTS: Thirty-seven patients with a total of 74 levels were
      analyzed. Clinical and radiographic outcome measures including central canal area
      (Delta = +17.2 mm2), mean disk height (Delta = +3 mm), and foraminal area (Delta
      = +9.9 mm2) revealed significant improvement compared with before surgery (P <=
      0.05). Patients with severe FD (grade 4) were more likely to have FT >= 12
      degrees (32.3%) than patients without/mild (grades 0 and 1; 10%) or moderate FD
      (grades 2 and 3; 13%), P <= 0.05. FD and FT did not affect disk height
      restoration, foraminal area, canal surface area, or clinical outcome measures (P
      >= 0.05). CONCLUSIONS: Indirect decompression of neural elements in ELIF is not
      impaired by FD and FT are not relative contraindications in patients undergoing
      ELIF.

PMID- 27888085
TI  - High-Definition Fiber Tractography in Evaluation and Surgical Planning of
      Thalamopeduncular Pilocytic Astrocytomas in Pediatric Population: Case Series and
      Review of Literature.
AB  - OBJECTIVE: Thalamopeduncular tumors (TPTs) of childhood present a challenge for
      neurosurgeons due to their eloquent location. Preoperative fiber tracking
      provides total or near-total resection, without additional neurologic deficit.
      High-definition fiber tractography (HDFT) is an advanced white matter imaging
      technique derived from magnetic resonance imaging diffusion data, shown to
      overcome the limitations of diffusion tensor imaging. We aimed to investigate
      alterations of corticospinal tract (CST) and medial lemniscus (ML) caused by TPTs
      and to demonstrate the application of HDFT in preoperative planning. METHODS:
      Three pediatric patients with TPTs were enrolled. CSTs and MLs were evaluated for
      displacement, infiltration, and disruption. The relationship of these tracts to
      tumors was identified and guided surgical planning. Literature was reviewed for
      publications on pediatric thalamic and TPTs that used diffusion imaging. RESULTS:
      Two patients had histologic diagnosis of pilocytic astrocytoma. One patient whose
      imaging suggested a low-grade glioma was managed conservatively. All tracts were
      displaced (1 CST anteriorly, 2 CSTs, 1 ML anteromedially, 1 ML medially, and 1 ML
      posteromedially). Literature review revealed 2 publications with 15 pilocytic
      astrocytoma cases, which investigated CST only. The condition of sensory pathway
      or anteromedial displacement of the CST in these tumors was not reported
      previously. CONCLUSIONS: Displacement patterns of the perilesional fiber bundles
      by TPTs are not predictable. Fiber tracking, preferably HDFT, should be part of
      preoperative planning to achieve maximal extent of resection for longer survival
      rates in this young group of patients, while preserving white matter tracts and
      thus quality of life.

PMID- 27888086
TI  - Effects of Smoking on Subjective and Objective Measures of Pain Intensity,
      Functional Impairment, and Health-Related Quality of Life in Lumbar Degenerative
      Disk Disease.
AB  - BACKGROUND: Numerous studies assessed the effects of smoking on lumbar
      degenerative disk disease (DDD); they focused on patient-reported outcome
      measures (PROMs) and yielded conflicting results. METHODS: In this 2-center study
      on consecutive patients receiving surgical treatment for lumbar DDD, subjective
      functional impairment (SFI) in terms of PROMs including visual analog scale back
      and leg pain, Roland-Morris, Oswestry Disability Index, Euro-Qol-5D, and a Short
      Form 12 physical component summary was determined at baseline, 3 days, 6 weeks, 6
      months, and 1 year postoperatively. Age- and sex-adjusted T-scores of objective
      functional impairment (OFI) were determined using the Timed Up and Go test up to
      6 weeks postoperatively. The responder status was defined by the minimal
      clinically important difference. RESULTS: We analyzed 375 patients (n = 96
      [25.6%] smokers and n = 279 [74.4%] nonsmokers). SFI on any of the PROMs before
      treatment was similar in smokers and nonsmokers. Smokers were more likely to have
      OFI in univariate logistic regression analysis (95% confidence interval 1.31
      3.37, P = 0.002). In multivariate analysis, however, this relationship became
      insignificant (95% confidence interval 0.85-2.38, P = 0.184). The smoking status
      had no predictive capacity on the 6-week SFI or OFI responder status, and there
      were no differences in any of the PROMs until the 1-year follow-up. CONCLUSIONS:
      PROMs measuring SFI for pain intensity, functional impairment, and health-related
      quality of life were similar in smokers and nonsmokers before surgery for lumbar
      DDD, as well as postoperatively. The smoking status has negligible impact on the
      Timed Up and Go test, which appears to be a robust assessment tool for OFI.

PMID- 27888087
TI  - Coiling of a Ruptured Large Internal Carotid Artery Aneurysm via Extracranial
      Intracranial Saphenous Vein Bypass Graft Just After Proximal Ligation of the
      Internal Carotid Artery.
AB  - BACKGROUND: Combined direct and endovascular surgery has been performed to treat
      large to giant internal carotid artery (ICA) aneurysms. This report describes
      successful treatment of a large ICA aneurysm by coiling of the aneurysm via an
      extracranial-intracranial saphenous vein (SV) graft just after bypass and ICA
      proximal ligation. CASE DESCRIPTION: A 66-year-old woman presented with a left
      ICA supraclinoid aneurysm with progressive visual field defect and impaired
      visual acuity in the left eye. While waiting for scheduled surgery, she
      experienced a subarachnoid hemorrhage. An extracranial-intracranial high-flow
      bypass using an SV graft and proximal ligation of the ICA were performed. Coiling
      of the aneurysm was immediately performed successfully via the SV bypass graft.
      The patient experienced no new neurologic deficit after this treatment. Follow-up
      radiologic evaluations using magnetic resonance imaging and magnetic resonance
      angiography revealed complete aneurysm occlusion. CONCLUSIONS: Aneurysm coiling
      via an extracranial-intracranial SV bypass graft could offer an alternative when
      an antegrade access route to the ICA is not used because of prior parent artery
      ligation.

PMID- 27888088
TI  - Endoscopic Endonasal Management of Rare Sellar Lesions: Clinical and Surgical
      Experience of 78 Cases and Review of the Literature.
AB  - OBJECTIVE: In the present study we aim to provide further definition of a group
      of rare sellar diseases treated by the endoscopic endonasal approach. METHODS:
      The study was a retrospective analysis of data obtained from a series of 1729
      patients who underwent endoscopic endonasal surgery at 2 academic institutions
      (Universita degli Studi di Napoli Federico II, Naples, Italy between January 1997
      and December 2013 and the Wexner Medical Center at The Ohio State University
      between July 2010 and September 2015). Clinical charts, operative notes, and
      pathology reports were examined. RESULTS: A total of 346 cases were identified to
      have nonadenomatous diseases. Applying the Rosner test for outliers assisted in
      excluding relatively frequent lesions. The final cohort of rare sellar diseases
      comprised 78 patients. Arachnoid cysts were the most frequently encountered
      sellar lesion (12 patients, 15%), followed by metastasis (11 cases, 14%),
      followed by hypophysitis (8 cases, 10%), oncocytoma, and glioma (6 cases, 8%
      each). The most frequent clinical findings were headache (28%) and visual
      disorders (80%). A standard endoscopic endonasal approach was performed in 44
      patients (56%), and an extended approach was carried out in 34 patients (44%).
      Tumor removal was gross total in 53% of patients, subtotal in 19%, and partial in
      21%. Postoperative endocrinologic and visual deficit evaluation showed
      improvements in endocrine function in 8 patients (10%) and in visual disorders in
      13 (16%). Postoperative complications arose in 28% of cases, mostly represented
      by diabetes insipidus (10%). CONCLUSIONS: Endoscopic endonasal approaches offer
      some specific benefits in the treatment of these patients.

PMID- 27888089
TI  - Quantitative Measurements of the Skull Base and Craniovertebral Junction in
      Congenital Occipitalization of the Atlas: A Computed Tomography-Based Anatomic
      Study.
AB  - OBJECTIVE: To study the craniovertebral junction and determine the anatomic
      characteristics of occipitalization of the atlas (OC) by computed tomography (CT)
      imaging. METHODS: We retrospectively reviewed 80 cases of patients with OC who
      underwent cervical CT scanning between March 2012 and March 2014. Forty healthy
      subjects were recruited as a control cohort. Fusion pattern and associated
      osseous anomalies were recorded. Fifteen linear quantitative parameters were
      measured to study the outlet of the foramen magnum, angular dimension of the
      skull base, posterior cranial fossa, and height of the odontoid process. RESULTS:
      The most common fusion pattern was the complete osseous fusion (83.75%). Fifty
      four patients (67.5%) presented with other osseous anomalies. Measurements of the
      OC group, such as the length of the clivus, cranial canal angle, and height of
      the odontoid process, were significantly different than those of the control
      group. The correlation analysis showed that the C1 lateral facet inclination was
      significantly correlated with the age of onset. CONCLUSIONS: The outlet of the
      foramen magnum is severely impaired in patients with OC, and the presence of
      other osseous anomalies is common. Deformity is not confined to the region of the
      assimilated atlas; the clivus and odontoid process are also shorter than normal.
      The lateral facet inclination likely influences disease progression.

PMID- 27888090
TI  - Rationale and design of Mi-CARE: The mile square colorectal cancer screening,
      awareness and referral and education project.
AB  - Although colorectal cancer (CRC) is largely preventable through identification of
      pre-cancerous polyps through various screening modalities, morbidity and
      mortality rates remain a challenge, especially in African-American, Latino, low
      income and uninsured/underinsured patients. Barriers to screening include cost,
      access to health care facilities, lack of recommendation to screen, and
      psychosocial factors such as embarrassment, fear of the test, anxiety about
      testing preparation and fear of a cancer diagnosis. Various intervention
      approaches to improve CRC screening rates have been developed. However,
      comparative effectiveness research (CER) to investigate the relative performance
      of different approaches has been understudied, especially across different real
      life practice settings. Assessment of differential efficacy across diverse
      vulnerable populations is also lacking. The current paper describes the rationale
      and design for the Mile Square Colorectal Cancer Screening, Awareness and
      Referral and Education Project (Mi-CARE), which aims to increase CRC screening
      rates in 3 clinics of a large Federally Qualified Health Center (FQHC) by
      reducing prominent barriers to screening for low-income, minority and underserved
      patients. Patients attending these clinics will receive one of three
      interventions to increase screening uptake: lay patient navigator (LPN)-based
      navigation, provider level navigation, or mailed birthday CRC screening
      reminders. The design of our program allows for comparison of the effectiveness
      of the tailored interventions across sites and patient populations. Data from Mi
      CARE may help to inform the dissemination of tailored interventions across FQHCs
      to reduce health disparities in CRC.

PMID- 27888091
TI  - Patient and clinical characteristics that heighten risk for heart failure
      readmission.
AB  - BACKGROUND: Within 30 days of hospital discharge, heart failure (HF) readmission
      rates nationally accumulate to more than 20%. Due to this high rate of unplanned
      re-hospitalization, predictive models are needed to identify patients who pose
      the highest readmission risk. OBJECTIVE: To evaluate the diagnosis and timing and
      to identify patient and clinical characteristics associated with 30 day
      readmissions among HF patients. METHODS: A retrospective analysis of electronic
      health records was conducted to study HF admissions during the period October
      2008 to November 2014. Patients with a primary discharge diagnosis consistent
      with HF were included. Descriptive statistics were used to compare the readmitted
      and non-readmitted cohorts. Logistic regression was used to develop a predictive
      model to determine patient and clinical variables associated with 30 day
      readmission. RESULTS: Characteristics of the study cohort (n = 2420) are: a mean
      age of 72, predominantly male (55%), white (55%), currently not employed (91%),
      and utilizing Medicare as a payer (68%). Overall, 42% were married. Over the
      study time period there were 394 (16.3%) 30 day readmissions after 2420
      hospitalizations. The 3 most common reasons for readmission were HF (36.0%),
      renal disorders (8.4%), and other cardiac diseases (6.9%). Analysis showed that
      11.9% of patients readmitted during days 0-3, 15.2% during days 4-7, 31.5% during
      days 8-15, and 41.4% during days 16-30. The final multivariate predictive model
      included 5 variables that were associated with an increased risk for 30-day
      readmission: employment status as retired or disabled, > 1 emergency department
      visit in the past 90 days, length of stay >5 days during index visit, and a BUN
      value > 45 mg/dL. CONCLUSION: This study provides a deeper understanding of
      patient and clinical characteristics that are associated with readmission in HF.
      Evaluation of these characteristics will provide additional information to guide
      strategies meant to reduce HF readmission rates.

PMID- 27888092
TI  - Classifying pharmacists' interventions recorded in observational databases: Are
      they all necessary and appropriate?
AB  - Over the past 25 years in various countries, researchers have developed tools for
      recording pharmacist's interventions (PIs) and observational databases aimed at
      the exhaustive collection of these interventions. The large amount of published
      data contrasts strikingly with the fact that little attention has been paid to
      defining the different types of PIs from a theoretical point of view. Whatever
      the paper we read on this topic, each PI is presented as necessary and
      appropriate. We suggest this customary approach is biased and that the reality is
      somewhat more subtle. In order to better reflect the real world, we propose a new
      approach to the classification of PIs that is based on whether they are present
      or absent in observational databases, and we explain how to identify the absent
      ones. Present and absent PIs can be subdivided in two additional categories:
      appropriate and inappropriate ones. This additional classification should
      encourage pharmacists to critically examine and evaluate their practice and
      subsequently improve their ability to identify drug related problems in clinical
      practice.

PMID- 27888093
TI  - Randomized trial of rATg/Daclizumab vs. rATg/Alemtuzumab as dual induction
      therapy in renal transplantation: Results at 8years of follow-up.
AB  - Our goal in using dual induction therapy is to bring the kidney transplant
      recipient closer (through more effectively timed lymphodepletion) to an optimally
      immunosuppressed state. Here, we report long-term results of a prospective
      randomized trial comparing (Group I,N=100) rATG/Dac (3 rATG, 2 Dac doses) vs.
      (Group II,N=100) rATG/Alemtuzumab(C1H) (1 dose each), using reduced tacrolimus
      dosing, EC-MPS, and early corticosteroid withdrawal. Lower EC-MPS dosing was
      targeted in Group II to avoid severe leukopenia. Median follow-up was 96mo post
      transplant. There were no differences in 1st BPAR (including borderline) rates:
      10/100 vs. 9/100 in Groups I and II during the first 12mo(P=0.54), and 20/100 vs.
      20/100 throughout the study(P=0.90). Equally favorable renal function was
      maintained in both treatment arms(N.S.). While not significant, more patients in
      Group II experienced graft loss, 25/100 vs. 18/100 in Group I(P=0.23). Actuarial
      patient/graft survival at 96mo was 92%/83% vs. 85%/73% in Groups I and II(N.S.).
      DWFG-due-to-infection(N.S.), EC-MPS withholding-due-to-leukopenia during the
      first 2mo(P=0.03), and incidence of viral infections(P=0.09) were higher in Group
      II, whereas EC-MPS withholding-due-to-GI symptoms was higher in Group I(P=0.009).
      No other adverse event differences were observed. While long-term anti-rejection
      and renal function efficacy were demonstrated in both treatment arms, slight over
      immunosuppression of Group II patients occurred.

PMID- 27888094
TI  - Nano-analyses of wear particles from metal-on-metal and non-metal-on-metal dual
      modular neck hip arthroplasty.
AB  - Increased failure rates due to metallic wear particle-associated adverse local
      tissue reactions (ALTR) is a significant clinical problem in resurfacing and
      total hip arthroplasty. Retrieved periprosthetic tissue of 53 cases with
      corrosion/conventional metallic wear particles from 285 revision operations for
      ALTR was selected for nano-analyses. Three major classes of hip implants
      associated with ALTR, metal-on-metal hip resurfacing arthroplasty (MoM HRA) and
      large head total hip replacement (MoM LHTHA) and non-metal-on-metal dual modular
      neck total hip replacement (Non-MoM DMNTHA) were included. The size, shape,
      distribution, element composition, and crystal structure of the metal particles
      were analyzed by conventional histological examination and electron microscopy
      with analytic tools of 2D X-ray energy dispersive spectrometry and X-ray
      diffraction. Distinct differences in size, shape, and element composition of the
      metallic particles were detected in each implant class which correlate with the
      histological features of severity of ALTR and variability in implant performance.

PMID- 27888095
TI  - Modulation of voltage-gated conductances of retinal horizontal cells by UV
      excited TiO2 nanoparticles.
AB  - This study examines the ability of optically-excited titanium dioxide
      nanoparticles to influence voltage-gated ion channels in retinal horizontal
      cells. Voltage clamp recordings were obtained in the presence and absence of TiO2
      and ultraviolet laser excitation. Significant current changes were observed in
      response to UV light, particularly in the -40 mV to +40 mV region where voltage
      gated Na+ and K+ channels have the highest conductance. Cells in proximity to UV
      excited TiO2 exhibited a left-shift in the current-voltage relation of around 10
      mV in the activation of Na+ currents. These trends were not observed in control
      experiments where cells were excited with UV light without being exposed to TiO2.
      Electrostatic force microscopy confirmed that electric fields can be induced in
      TiO2 with UV light. Simulations using the Hodgkin-Huxley model yielded results
      which agreed with the experimental data and showed the I-V characteristics of
      individual ion channels in the presence of UV-excited TiO2.

PMID- 27888096
TI  - Development, validation and psychometric properties of the Arabic version of the
      Orofacial Esthetic Scale: OES-Ar.
AB  - PURPOSE: This study aimed at developing the Arabic version of the Orofacial
      Esthetic Scale (OES-Ar) and to investigate its psychometric properties among
      Arabic-speaking population with and without esthetic impairments. METHODS:
      Translation and cross-cultural adaptation was done according to the standard
      guidelines. Internal consistency was assessed on 230 participants. For test
      retest reliability, 50 subjects with natural teeth were recalled within a period
      of 2 weeks. Validity of the OES-Ar was tested by construct, convergent, and
      discriminant validity tests. Responsiveness to esthetic changes was assessed in
      60 patients. RESULTS: The results showed excellent internal consistency with
      Cronbach's alpha value of 0.92 and inter-item correlation average value of 0.60.
      The ICC values ranged from 0.87 to 0.96 which indicated excellent agreement.
      Construct validity of the OES-Ar was confirmed to be one-factor structure (one
      dimensional). For convergent validity, a significant correlation was found
      between OES summary score and overall impression of the orofacial esthetic as
      well as between OES summary score and the summary score of the three questions of
      the OHIP-49Ar related to esthetic. The discriminant validity test revealed
      significant differences between different study groups (P<0.001). Responsiveness
      to treatment was confirmed by significant differences between pre- and post
      treatment OES total summary score (P<0.001). CONCLUSION: The OES-Ar has excellent
      psychometric properties making it valuable instrument to assess orofacial
      esthetics in Arabic-speaking patients.

PMID- 27888097
TI  - Rab7a regulates cell migration through Rac1 and vimentin.
AB  - Rab7a, a small GTPase of the Rab family, is localized to late endosomes and
      controls late endocytic trafficking. The discovery of several Rab7a interacting
      proteins revealed that Rab7a function is closely connected to cytoskeletal
      elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible
      for the movement of Rab7a-positive vesicles and/or organelles on microtubule
      tracks, but also directly interacts with Rac1, a fundamental regulator of actin
      cytoskeleton, and with peripherin and vimentin, two intermediate filament
      proteins. Considering all these interactions and, in particular, the fact that
      Rac1 and vimentin are key factors for cellular motility, we investigated a
      possible role of Rab7a in cell migration. We show here that Rab7a is needed for
      cell migration as Rab7a depletion causes slower migration of NCI H1299 cells
      affecting cell velocity and directness. Rab7a depletion negatively affects
      adhesion and spreading onto fibronectin substrates, altering beta1-integrin
      activation, localization and intracellular trafficking, and myosin X
      localization. In fact, Rab7a-depleted cells show 40% less filopodia and active
      integrin accumulates at the leading edge of migrating cells. Furthermore, Rab7a
      depletion decreases the amount of active Rac1 but not its abundance and reduces
      the number of cells with vimentin filaments facing the wound, indicating that
      Rab7a has a role in the orientation of vimentin filaments during migration. In
      conclusion, our results demonstrate a key role of Rab7a in the regulation of
      different aspects of cell migration.

PMID- 27888098
TI  - Identification of novel peptide motifs in the serpin maspin that affect vascular
      smooth muscle cell function.
AB  - Maspin is a non-inhibitory member of the serpin family that affects cell
      behaviours related to migration and survival. We have previously shown that
      peptides of the isolated G alpha-helix (G-helix) domain of maspin show
      bioactivity. Migration, invasion, adhesion and proliferation of vascular smooth
      muscle cells (VSMC) are important processes that contribute to the build-up of
      atherosclerotic plaques. Here we report the use of functional assays of these
      behaviours to investigate whether other maspin-derived peptides impact directly
      on VSMC; focusing on potential anti-atherogenic properties. We designed 18 new
      peptides from the structural moieties of maspin above ten amino acid residues in
      length and considered them beside the existing G-helix peptides. Of the novel
      peptides screened those with the sequences of maspin strand 4 and 5 of beta sheet
      B (S4B and S5B) reduced VSMC migration, invasion and proliferation, as well as
      increasing cell adhesion. A longer peptide combining these consecutive sequences
      showed a potentiation of responses, and a 7-mer contained all essential elements
      for functionality. This is the first time that these parts of maspin have been
      highlighted as having key roles affecting cell function. We present evidence for
      a mechanism whereby S4B and S5B act through ERK1/2 and AMP-activated protein
      kinase (AMPK) to influence VSMC responses.

PMID- 27888099
TI  - Bivalent kinetic binding model to surface plasmon resonance studies of antigen
      antibody displacement reactions.
AB  - Molecular and functional analysis of small molecule binding to protein can
      provoke insights into cellular signaling and regulatory systems as well as
      facilitate pharmaceutical drug discovery. In label free small molecule detection
      the displacement assay format can be applied. This is beneficial because
      displacement of high molecular weight receptors is detected instead of low
      molecular weight ligand as in classical binding analysis. Thus, detection limit
      is potentially lowered. Using the influenza haemagglutinin (HA) peptide binding
      to mono or bivalent anti-haemagglutinin peptide antibody displacement assay
      formats could be established. The exact time resolved analysis of binding and
      dissolution of ligand HA and anti-Haemagglutinin peptide antibody was achieved
      with surface plasmon resonance (SPR) spectroscopy. Mathematical models could be
      developed from kinetic equations of ligand binding to mono or bivalent
      antibodies. With this, an accurate simulation of the SPR results was reached. The
      simulation plot had to be exactly adjusted to the SPR results to determine all
      kinetic rate constants defining ligand and receptor binding kinetics. Large
      variations in receptor concentration gave almost identical rate constants in
      binding. It became obvious that rebinding is in any case not necessary to
      understand the binding kinetics of our model system HA/anti-HA. Maximum decline
      of SPR response could be used to determine ligand concentrations in analyte.

PMID- 27888100
TI  - Harnessing Wharton's jelly stem cell differentiation into bone-like nodule on
      calcium phosphate substrate without osteoinductive factors.
AB  - : An important aim of bone regenerative medicine is to design biomaterials with
      controlled chemical and topographical features to guide stem cell fate towards
      osteoblasts without addition of specific osteogenic factors. Herein, we find that
      sprayed bioactive and biocompatible calcium phosphate substrates (CaP) with
      controlled topography induce, in a well-orchestrated manner, Wharton's jelly stem
      cells (WJ-SCs) differentiation into osteoblastic lineage without any osteogenic
      supplements. The resulting WJ-SCs commitment exhibits features of native bone,
      through the formation of three-dimensional bone-like nodule with osteocyte-like
      cells embedded into a mineralized type I collagen. To our knowledge, these
      results present the first observation of a whole differentiation process from
      stem cell to osteocytes-like on a synthetic material. This suggests a great
      potential of sprayed CaP and WJ-SCs in bone tissue engineering. These unique
      features may facilitate the transition from bench to bedside and the development
      of successful engineered bone. STATEMENT OF SIGNIFICANCE: Designing materials to
      direct stem cell fate has a relevant impact on stem cell biology and provides
      insights facilitating their clinical application in regenerative medicine.
      Inspired by natural bone compositions, a friendly automated spray-assisted system
      was used to build calcium phosphate substrate (CaP). Sprayed biomimetic solutions
      using mild conditions led to the formation of CaP with controlled physical
      properties, good bioactivity and biocompatibility. Herein, we show that via
      optimization of physical properties, CaP substrate induce osteogenic
      differentiation of Wharton's jelly stem cells (WJ-SCs) without adding osteogenic
      supplement factors. These results suggest a great potential of sprayed CaP and WJ
      SCs in bone tissue engineering and may facilitate the transition from bench to
      beside and the development of clinically successful engineered bone.

PMID- 27888101
TI  - Post-hatching brain morphogenesis and cell proliferation in the pulse-type
      mormyrid Mormyrus rume proboscirostris.
AB  - The anatomical organization of African Mormyrids' brain is a clear example of
      departure from the average brain morphotype in teleosts, probably related to
      functional specialization associated to electrosensory processing and sensory
      motor coordination. The brain of Mormyrids is characterized by a well-developed
      rhombencephalic electrosensory lobe interconnected with relatively large
      mesencephalic torus semicircularis and optic tectum, and a huge and complex
      cerebellum. This unique morphology might imply cell addition from
      extraventricular proliferation zones up to late developmental stages. Here we
      studied the ontogeny of these brain regions in Mormyrus rume proboscirostris from
      embryonic to adult stages by classical histological techniques and 3D
      reconstruction, and analyzed the spatial-temporal distribution of proliferating
      cells, using pulse type BrdU labeling. Brain morphogenesis and maturation
      progressed in rostral-caudal direction, from 4day old free embryos, through
      larvae, to juveniles whose brain almost attained adult morphological complexity.
      The change in the relative size of the telencephalon, and mesencephalic and
      rhombencephalic brain regions suggest a developmental shift in the relative
      importance of visual and electrosensory modalities. In free embryos,
      proliferating cells densely populated the lining of the ventricular system.
      During development, ventricular proliferating cells decreased in density and
      extension of distribution, constituting ventricular proliferation zones. The
      first recognizable one was found at the optic tectum of free embryos. Several
      extraventricular proliferation zones were found in the cerebellar divisions of
      larvae, persisting along life. Adult M. rume proboscirostris showed scarce
      ventricular but profuse cerebellar proliferation zones, particularly at the
      subpial layer of the valvula cerebelli, similar to lagomorphs. This might
      indicate that adult cerebellar proliferation is a conserved vertebrate feature.

PMID- 27888102
TI  - The phosphatidyl inositol 3 kinase pathway does not suppress activation of the
      ARF and BIM genes by deregulated E2F1 activity.
AB  - The transcription factor E2F plays crucial roles in tumor suppression by
      activating pro-apoptotic genes such as the tumor suppressor ARF. The regulation
      of the ARF gene is distinct from that of growth-related E2F targets, in that it
      is specifically activated by deregulated E2F activity, induced by over-expression
      of E2F or forced inactivation of pRB, but not by physiological E2F activity
      induced by growth stimulation. The phosphatidyl inositol 3 kinase (PI3K) pathway
      was reported to suppress expression of some atypical pro-apoptotic genes by over
      expressed E2F1. However, the effects of the PI3K pathway on the distinct
      regulation of typical pro-apoptotic E2F targets have not been elucidated. We
      examined whether the PI3K pathway suppressed activation of the typical pro
      apoptotic E2F targets ARF and BIM. Activation of the PI3K pathway by growth
      stimulation or introduction of a constitutively active Akt/PKB did not reduce
      induction of ARF or BIM gene expression or activation of their promoters by over
      expressed E2F1. These results suggest that the PI3K pathway does not suppress
      induction of typical pro-apoptotic genes that are selectively activated by
      deregulated E2F1.

PMID- 27888103
TI  - Luteolin improves non-alcoholic fatty liver disease in db/db mice by inhibition
      of liver X receptor activation to down-regulate expression of sterol regulatory
      element binding protein 1c.
AB  - In this study, we report that daily administration of luteolin for 8 weeks
      improved hepatic steatosis by repressing hepatic TG accumulation and increasing
      glycogen storage. Luteolin inhibited hepatic de novo lipid synthesis by
      regulating the LXR-SREBP-1c signaling pathway, which is over-activated in the
      livers of db/db mice. Further in vitro studies revealed that luteolin can
      competitively bind to the ligand binding domain to suppress the LXR activation
      induced by an LXR agonist and high glucose, thereby decreasing TG accumulation in
      HepG2 cells and primary hepatocytes. Taken together, our results indicate that
      luteolin can abolish lipid accumulation induced by LXR-SREBP-1c activation both
      in vivo and in vitro, and may have potential as a therapeutic agent for treating
      NAFLD.

PMID- 27888104
TI  - Inhibition of ERK activity enhances the cytotoxic effect of peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonists in HeLa cells.
AB  - In this study, we examined whether the peroxisome proliferator-activated receptor
      gamma (PPARgamma) agonists, ciglitazone (CGZ) and troglitazone (TGZ), induce cell
      death in human cervical cancer HeLa cells. The cells were treated with a range of
      CGZ or TGZ doses for 24 or 48 h. Low concentrations of CGZ (<=10 MUM) or TGZ
      (<=20 MUM) had no effect on cell viability whereas higher doses induced cell
      death in a time- and dose-dependent manner as evidenced by the detection of
      activated caspase-3 and PARP cleavage. Treatment with the PPARgamma antagonist
      GW9662 followed by PPARgamma agonists did not increase CGZ- or TGZ-induced cell
      death, indicating that PPARgamma agonists induced HeLa cell death independently
      of PPARgamma. Moreover, ERK1/2 activation was observed at a CGZ concentration of
      25 MUM and a TGZ concentration of 35 MUM, both of which induced cell death. To
      elucidate the role of ERK1/2 activated by the two PPARgamma agonists, the effect
      of U0126, an inhibitor of ERK1/2, on PPARgamma-agonist-induced cell death was
      examined. Treatment with 10 or 20 MUM U0126 followed by CGZ or TGZ induced the
      down-regulation of ERK1/2 activity and a decrease in Bcl-2 expression accompanied
      by the collapse of mitochondrial membrane potential, which in turn significantly
      enhanced CGZ- or TGZ-induced apoptotic cell death. Our results suggest that
      PPARgamma agonists are capable of inducing apoptotic cell death in HeLa cells
      independently of PPARgamma and that inhibition of ERK1/2 activity offers a
      strategy to enhance the cytotoxicity of PPARgamma agonists in the treatment of
      cervical cancer.

PMID- 27888105
TI  - Efficient ex vivo delivery of chemically modified messenger RNA using lipofection
      and magnetofection.
AB  - Recently, chemically modified mRNA (cmRNA) therapeutics have been the subject of
      extensive application-oriented research in both academia and industry as a safer
      alternative for gene and recombinant protein therapies. However, the lack of an
      efficient delivery system hinders widespread application. Here we used ~100-nm
      lipoplexes and magnetic lipoplexes that can protect cmRNA from RNases and
      efficiently deliver it into muscle and fat tissues as well as to the endothelium
      of the carotid artery. Establishing magnetofection for ex vivo cmRNA delivery for
      the first time, we suggest this method for potential enhanced and targeted
      delivery of cmRNA. This study introduces optimal cmRNA complexes with high ex
      vivo efficiency as good candidates for further in vivo cmRNA delivery.

PMID- 27888106
TI  - Long non-coding RNA NEAT1 facilitates pancreatic cancer progression through
      negative modulation of miR-506-3p.
AB  - Recently, long non-coding RNAs (lncRNAs) have been shown to have critical
      regulatory roles in tumourigenesis. Increasing evidence has suggested that lncRNA
      NEAT1 has been implicated in various types of human cancer. However, the
      potential biological roles and regulatory mechanisms of NEAT1 in pancreatic
      cancer (PC) remains unclear. Here, we found that the expression level of NEAT1
      was higher in PC tissues compared to the corresponding non-tumor tissues.
      Besides, our findings indicate that high NEAT1 expression level is closely
      correlated with tumor progression and poor survival in PC patients. Furthermore,
      we also found that knockdown of NEAT1 remarkably suppressed cell proliferation by
      inducing cell cycle arrest and apoptosis promotion in PC cells. Moreover,
      bioinformatics analysis and luciferase reporter assay revealed that NEAT1
      directly bound to the miR-506-3p, which has been reported to act as a tumor
      suppressor in diverse cancers. Additionally, our results confirmed that the tumor
      promoting effects of NEAT1 in PC cells is at least partly through negative
      modulation of miR-506-3p. Overall, our results suggested that NEAT1 functions as
      an oncogenic lncRNA in PC, which could be a novel diagnostic and therapeutic
      target for PC.

PMID- 27888108
TI  - Hypoxanthine causes endothelial dysfunction through oxidative stress-induced
      apoptosis.
AB  - Endothelial cell injury and dysfunction caused by reactive oxygen species (ROS)
      are implicated in the pathogenesis of vascular diseases. ROS are generated and
      hypoxanthine is degraded by xanthine oxidase. Smoking and alcohol consumption are
      associated with an increased level of hypoxanthine. We aimed to study the direct
      role of hypoxanthine in endothelial dysfunction in human umbilical vascular
      endothelial cells (HUVECs). Hypoxanthine induced cell death and production of
      ROS. Furthermore, hypoxanthine induced apoptosis through regulation of protein
      expression related to apoptosis. When cells were pretreated with N-acetylcysteine
      or a pancaspase inhibitor (Z-VAD-fmk) and stimulated with hypoxanthine, Z-VAD-fmk
      and N-acetylcysteine prevented hypoxanthine-induced apoptosis by inhibiting the
      ROS production and caspase pathway. Thus, an increased extracellular
      concentration of hypoxanthine induces endothelial dysfunction through ROS
      production and regulates expression of apoptosis-related proteins in HUVECs.
      These effects are expected to be associated with some vascular diseases.

PMID- 27888107
TI  - Sodium butyrate attenuates soybean oil-based lipid emulsion-induced increase in
      intestinal permeability of lipopolysaccharide by modulation of P-glycoprotein in
      Caco-2 cells.
AB  - Down-regulation of intestinal P-glycoprotein (P-gp) by soybean oil-based lipid
      emulsion (SOLE) may cause elevated intestinal permeability of lipopolysaccharide
      (LPS) in patients with total parenteral nutrition, but the appropriate
      preventative treatment is currently limited. Recently, sodium butyrate (NaBut)
      has been demonstrated to regulate the expression of P-gp. Therefore, this study
      aimed to address whether treatment with NaBut could attenuate SOLE-induced
      increase in intestinal permeability of LPS by modulation of P-gp in vitro. Caco-2
      cells were exposed to SOLE with or without NaBut. SOLE-induced down-regulation of
      P-gp was significantly attenuated by co-incubation with NaBut. Nuclear
      recruitment of FOXO 3a in response to NaBut was involved in P-gp regulation.
      Transport studies revealed that SOLE-induced increase in permeability of LPS was
      significantly attenuated by co-incubation with NaBut. Collectively, our results
      suggested that NaBut may be a potentially useful medication to prevent SOLE
      induced increase in intestinal permeability of LPS.

PMID- 27888109
TI  - Ephestia kuehniella tolerance to Bacillus thuringiensis Cry1Aa is associated with
      reduced oligomer formation.
AB  - The basis of the different susceptibility of Ephestia kuehniella to the Cry1Aa
      and Cry1Ac delta-endotoxins from Bacillus thuringiensis kurstaki BNS3 was
      studied. Both toxins bound specifically to the BBMV of E. kuehniella. The result
      of the ligand blot showed that Cry1Ac bound to three putative receptors of about
      100, 65 and 80 kDa and Cry1Aa interacted only with a 100 kDa protein. Pronase
      digestion of the BBMV-bound toxins was used to analyze the toxin insertion. Both
      toxins inserted into the BBMV as monomers however, a 14 kDa peptide of alpha4
      alpha5 which correspond to the oligomeric form of this peptide was detected in
      case of Cry1Ac only. Analysis of the in vitro oligomerisation of these toxins in
      the presence of the BBMV of E. kuehniella showed reduced oligomer formation in
      case of Cry1Aa in comparison with Cry1Ac. Taken together, these results strongly
      suggest that the difference of toxicity between Cry1Aa and Cry1Ac to E.
      kuehniella is due to a deficient oligomerisation of Cry1Aa.

PMID- 27888110
TI  - Tubby domain superfamily protein is required for the formation of the 7S SNARE
      complex in Drosophila.
AB  - Tubby domain superfamily protein (TUSP) is a distant member of the Tubby-like
      protein (TULP) family. Although other TULPs play important roles in sensation,
      metabolism, and development, the molecular functions of TUSP are completely
      unknown. Here, we explore the function of TUSP in the Drosophila nervous system
      where it is expressed in all neurons. Tusp mutant flies exhibit a temperature
      sensitive paralysis. This paralysis can be rescued by tissue-specific expression
      of Tusp in the giant fibers and peripherally synapsing interneurons of the giant
      fiber system, a well-characterized neuronal circuit that mediates rapid escape
      behavior in flies. Consistent with this paralytic phenotype, we observed a
      profound reduction in the assembly of the ternary 7S SNARE complex that is
      required for neurotransmitter release despite seeing no changes in the expression
      of each individual SNARE complex component. Together, these data suggest TUSP is
      a novel regulator of SNARE assembly and, therefore, of neurotransmitter release.

PMID- 27888112
TI  - Satellite cell activation induced by aerobic muscle adaptation in response to
      endurance exercise in humans and rodents.
AB  - Although the requirement of satellite cells activation and expansion following
      injury, mechanical load or growth stimulus provoked by resistance exercise has
      been well established, their function in response to aerobic exercise adaptation
      remains unclear. A clear relationship between satellite cell expansion in fiber
      type specific myosin heavy chain and aerobic performance has been related,
      independent of myonuclear accretion or muscle growth. However, the trigger for
      this activation process is not fully understood yet and it seems to be a multi
      faceted and well-orchestrated process. Emerging in vitro studies suggest a role
      for metabolic pathways and oxygen availability for satellite cell activation,
      modulating the self-renewal potential and cell fate control. The goal of this
      review is to describe and discuss the current knowledge about the satellite cell
      activation and expansion in response to aerobic exercise adaptation in human and
      rodent models. Additionally, findings about the in vitro metabolic control, which
      seems be involved in the satellite cell activation and cell fate control, are
      presented and discussed.

PMID- 27888111
TI  - Neutralizing human recombinant antibodies against herpes simplex virus type 1
      glycoproteins B from a phage-displayed scFv antibody library.
AB  - The HSV-1 envelope glycoprotein B (gB) plays a critical role in virus entry into
      host cells. Neutralizing antibodies can therefore potentially prevent virus entry
      into target cells and cell-to-cell spread of infection. Our present study focused
      on the selection of neutralizing single-chain Fv (scFv) antibodies of a phage
      displayed nonimmune human scFv antibody library against gB of HSV-1. To enrich
      specific scFvs, two phage antibodies were isolated against amino acid residues 31
      43 derived from the N-terminal part of gB using panning technique. Two scFvs,
      scFv-gB1 and scFv-gB2, with frequencies of 45% and 20% were obtained from scFv
      clones after performing PCR and MvaI fingerprinting. In phage ELISA analysis,
      both gB1 and gB2 scFvs demonstrated high reactivity with the gB peptide. In the
      neutralization assay, scFv-gB1 and scFv-gB2 represented neutralizing effects of
      55% and 59%, respectively. Upon further enhancement of the neutralizing effects
      of these antibodies, they can be considered as new potential alternatives in the
      treatment and prophylaxis of HSV-1 infections.

PMID- 27888113
TI  - Circadian urinary citrate excretion in a rat model of exercise.
AB  - AIMS: Circadian rhythms are the approximate 24h biological cycles that function
      to prepare an organism for daily environmental changes. Circadian rhythms
      unquestionably play critical roles in metabolic homeostasis and the exercise has
      emerged as a strong non-photic time cue or zeitgeber in animal models and humans.
      Numerous studies about the effects of exercise on the citrate synthase activity
      have been published. Citrate is used to assess energy production or expenditure
      because it is a substrate of the Krebs Cycle, a cycle for oxidative energy
      production. MAIN METHODS: We tested the existence of a rhythmic urinary citrate
      excretion in a rat model that is made to exercise at six different points during
      the day. KEY FINDINGS: The data obtained by the enzyme assays were fitted to a
      mathematical model (Fourier series), showing for the first time, the existence of
      a distinct ultradian rhythm in the urinary citrate excretion. The aerobic
      exercise led to the increase in the period length of the ultradian rhythm and
      raised the acrophase value of the urinary citrate excretion. Therefore, the
      urinary citrate excretion pattern changed after exercise, showing a clear
      circadian rhythm fitted to the mathematical model. SIGNIFICANCE: The citrate
      urine samples could provide accurate data for ranking an individual's metabolic
      status. Using exercise to maintain the circadian clock at an appropriate phase
      and amplitude might be effective to prevent cardiometabolic disease development.

PMID- 27888114
TI  - Limonene reduces hyperalgesia induced by gp120 and cytokines by modulation of IL
      1 beta and protein expression in spinal cord of mice.
AB  - AIMS: We have investigated the antihyperalgesic effects of limonene in mice that
      received intrathecal injection of gp120. MAIN METHODS: Male Swiss mice received
      gp120, IL-1beta or TNF-alpha intrathecally or sterile saline as a control. A
      mechanical sensitivity test was performed at 2 and 3h after the injection. Spinal
      cord and blood samples were isolated for protein quantification. KEY FINDINGS:
      Intrathecal administration of gp120 increased mechanical sensitivity measured
      with an electronic Von Frey apparatus, at 2 and 3h after the injections. Limonene
      administered orally prior to gp120 administration significantly decreased this
      mechanical sensitivity at 3h after the gp120 injection. In addition, intrathecal
      injection of gp120 increased IL-1beta and IL-10 in serum, and limonene prevented
      the ability of gp120 to increase these cytokines. Limonene also inhibited TNF
      alpha and IL-1beta-induced mechanical hyperalgesia. Western blot assay
      demonstrated limonene was capable of increasing SOD expression in the cytoplasm
      of cells from spinal cord at 4h after intrathecal IL-1beta injection.
      SIGNIFICANCE: These results demonstrate that gp120 causes mechanical hyperalgesia
      and a peripheral increase in IL-1beta and IL-10, and that prior administration of
      limonene inhibits these changes. Also limonene modulates the activation of SOD
      expression in the spinal cord after spinal IL-1beta application. The ability of
      limonene to inhibit the mechanical hyperalgesia induced by gp120, TNF-alpha and
      IL-1beta emphasizes the anti-inflammatory action of limonene, specifically its
      ability to inhibit cytokine production and its consequences.

PMID- 27888115
TI  - Application of carbon nanotubes as the carriers of the cannabinoid, 2
      arachidonoylglycerol: Towards a novel treatment strategy in colitis.
AB  - AIMS: Treatment of colitis has remained a major clinical challenge. The
      cannabinoid, 2-arachidonoyglycerol (2-AG), has shown beneficial effects in
      colitis, however, poor solubility or rapid hydrolysis may limit its efficiency.
      According to the high biocompatibility of carbon nanotubes (CNTs) and their
      ability for controlled drug delivery, we aimed to prepare multi-walled CNTs-2-AG
      (MWCNTs-2-AG) complex in order to improve the pharmacological profile of 2-AG and
      evaluate the therapeutic potential of this nanocomplex in a rat model of colitis.
      MATERIALS AND METHODS: Aminated MWCNTs-2-AG complex was prepared using acidified
      MWCNTs and then characterized by Fourier transform infrared spectroscopy and
      transmission electron microscopy. In vitro cytotoxicity of MWCNTs was evaluated.
      Colitis was induced by colonic instillation of trinitrobenzene sulfonic acid
      (TNBS) and the effects of 2-AG solution and various types of MWCNTs on the
      colonic tissue damage, inflammation, and oxidative stress were evaluated. KEY
      FINDINGS: Aminated MWCNTs and MWCNTs-2-AG complex exhibited significantly lower
      cytotoxicity than acidified MWCNTs. Once daily intrarectal application of MWCNTs
      2-AG complex (containing 2mg/kg of 2-AG) 2days before and 8days after the
      induction of colitis effectively reduced the macroscopic and microscopic
      injuries, malondialdehyde, tumour necrosis factor-alpha, and interlukin-1beta
      concentrations, and myeloperoxidase activity. While, free 2-AG (2mg/kg), and
      acidified or aminated MWCNTs showed no beneficial effects. SIGNIFICANCE: Amino
      functionalized MWCNTs appear as the suitable carriers for 2-AG which provide a
      sustained concentration for this cannabinoid leading to the promising therapeutic
      effects in the experimental colitis.

PMID- 27888116
TI  - HPV16 induces a wasting syndrome in transgenic mice: Amelioration by dietary
      polyphenols via NF-kappaB inhibition.
AB  - Cancer patients often show a wasting syndrome for which there are little
      therapeutic options. Dietary polyphenols have been proposed for treating this
      syndrome, but their usefulness in cases associated with human papillomavirus
      (HPV)-induced cancers is unknown. We characterized HPV16-transgenic mice as a
      model of cancer cachexia and tested the efficacy of long-term oral
      supplementation with polyphenols curcumin and rutin. Both compounds were orally
      administered to six weeks-old HPV16-transgenic mice showing characteristic multi
      step skin carcinogenesis, for 24weeks. Skin lesions and blood, liver and spleen
      inflammatory changes were characterized histologically and hematologically.
      Hepatic oxidative stress, skeletal muscle mass and the levels of muscle pro
      inflammatory transcription factor NF-kappaB were also assessed. Skin
      carcinogenesis was associated with progressive, severe, systemic inflammation
      (leukocytosis, hepatitis, splenitis), significant mortality and cachexia.
      Curcumin and rutin totally suppressed mortality while reducing white blood cells
      and the incidence of splenitis and hepatitis. Rutin prevented muscle wasting more
      effectively than curcumin. Preservation of muscle mass and reduced hepatic
      inflammation were associated with down-regulation of the NF-kappaB canonical
      pathway and with reduced oxidative stress, respectively. These results point out
      HPV16-transgenic mice as a useful model for studying the wasting syndrome
      associated with HPV-induced cancers. Dietary NF-kappaB inhibitors may be useful
      resources for treating this syndrome.

PMID- 27888117
TI  - Testing Assumptions in Human Pain Models: Psychophysical Differences Between
      First and Second Pain.
AB  - : Acute pain arises from activation of myelinated (A delta) and unmyelinated (C)
      nociceptive afferents, leading to first (A-fiber) or second (C-fiber) pain
      sensations. The current study sought to investigate first and second pain within
      glabrous and hairy skin sites in human upper limbs. Fifty healthy adults (25
      male/25 female, 18-30 years old, mean = 20.5 +/- 1.4 years) participated in a
      psychophysical study investigating electronically rated, thermal first and second
      pain sensations within the glabrous skin at the palm and hairy skin of the
      forearm. Repeated measures analysis of variance indicated that the threshold for
      first pain was lower (more sensitive) than for second pain (P = .004), for
      glabrous as well as hairy skin, and thresholds at glabrous skin were higher than
      for hairy skin (P = .001). Hairy skin presented a steeper slope for testing,
      whereas there were no differences in slope between first and second pain. The
      study findings support assumptions associated with mechanistic differences
      between first and second pain sensations, while offering a novel method for
      producing first and second pain with the same thermal stimulus. Efforts to
      understand abnormalities among people with clinical pain and development of new
      therapeutic agents will benefit from specific psychophysical methods.
      PERSPECTIVE: This article presents a novel method for directly comparing first
      and second pain within the same thermal stimulus. The ability to directly compare
      first and second pain sensations can aid in understanding pain abnormalities in
      clinical pain and development of therapeutic aids.

PMID- 27888118
TI  - Increased Risk of New-Onset Fibromyalgia Among Chronic Osteomyelitis Patients:
      Evidence From a Taiwan Cohort Study.
AB  - : Chronic inflammation, which changes the neurotransmitter metabolism and kindles
      neuroendocrine system dysfunction in the central nervous system, might cause
      fibromyalgia (FM) formation. In FM patients without traditional FM risk factors,
      such as hypertension, hyperlipidemia, diabetes, sleep disorder, depression, and
      anxiety, the chronic inflammatory process is a possible risk factor for FM. Thus,
      we investigated whether chronic osteomyelitis (COM), a disease characterized by
      chronic inflammation, increases FM risk. Including data for 1 million enrollees,
      the Longitudinal Health Insurance Database was used, and 1,244 COM patients
      without FM history and 4,976 randomly selected sex- and age-matched control
      subjects without COM or FM history were extracted. The development of FM over a
      13-year follow-up period from 1999 to 2011 was evaluated, and FM risk was
      estimated using the Cox proportional regression model. The aforementioned FM risk
      factors were more common in COM patients, who had a significantly greater FM risk
      than did the control subjects. Compared with those who had no associated risk
      factors, patients with COM had a greater FM risk than did the control subjects
      (adjusted hazard ratio [aHR] = 1.32, 95% confidence interval [CI], .99-1.75).
      Younger people had an even greater risk (age younger than 35 years: aHR = 1.58,
      95% CI, 1.03-2.44; age 60 years or older: aHR = 1.03, 95% CI, .78-1.36). To our
      knowledge, this is the first study to link COM to an enhanced risk of FM
      development. The results imply that COM is a predictor of FM, suggesting that
      close follow-up for patients with COM is required to prevent FM, especially in
      younger populations. PERSPECTIVE: COM is associated with the augmented risk of
      developing FM, and rigorous treatments for COM patients might decrease the future
      risk of FM formation, especially in those with relatively younger ages.

PMID- 27888119
TI  - Prenatal phthalate, triclosan, and bisphenol A exposures and child visual-spatial
      abilities.
AB  - INTRODUCTION: During fetal development, sex steroids influence sexually dimorphic
      behaviors, such as visual-spatial abilities. Thus, endocrine disrupting chemicals
      that impact sex steroids during gestation may affect these behaviors. OBJECTIVE:
      We investigated the relationship between prenatal urinary phthalate metabolite,
      triclosan, and BPA concentrations and visual-spatial abilities in a prospective
      cohort of 198 mother-child dyads. METHODS: Data are from a prospective cohort in
      Cincinnati, OH (HOME Study). We measured nine phthalate metabolites, triclosan,
      and BPA in maternal urine samples collected at 16 and 26 weeks of gestation. We
      assessed children's visual-spatial abilities at 8 years of age using the Virtual
      Morris Water Maze (VMWM), a computerized version of the rodent Morris Water Maze.
      We quantified the covariate-adjusted change in the time or distance to complete
      the VMWM and time spent in the correct quadrant during a probe trial with an
      interquartile range increase in chemical concentrations using linear mixed models
      and linear regression, respectively. RESULTS: Boys completed the VMWM faster
      (4.1s; 95% CI:-7.1, -1.2) and in less distance (1.4 units; 95% CI:-2.8, 0) than
      girls. Overall, children with higher mono-n-butyl (MnBP), mono-benzyl (MBzP), and
      mono-carboxypropyl phthalate concentrations completed the VMWM in less time and
      distance than children with lower concentrations. For example, children with
      higher MnBP concentrations completed the VMWM in 0.9 less distance units (95% CI:
      1.8, -0.0). Child sex modified the association between MnBP and VMWM performance.
      In girls, higher MnBP concentrations were associated with longer time (1.7s; 95%
      CI: -0.7, 4.1) and shorter distance (-1.7 units; 95% CI: -2.8, -0.5), whereas in
      boys, it was associated with shorter time (-3.0s; 95% CI:-5.6, -0.4), but not
      distance (-0.1 units; 95% CI:1.4, 1.0). Other phthalate metabolites, triclosan,
      and BPA were not associated with VMWM performance, and sex did not consistently
      modify these associations. CONCLUSIONS: In this cohort, greater prenatal urinary
      concentrations of some phthalate metabolites were associated with improved VMWM
      performance, particularly among boys. Future studies should confirm these
      findings and determine if phthalates affect other hormonally sensitive aspects of
      child neurobehavior.

PMID- 27888121
TI  - In situ affinity purification of his-tagged protein A from Bacillus megaterium
      cultivation using recyclable superparamagnetic iron oxide nanoparticles.
AB  - This paper discusses the use of recyclable functionalized nanoparticles for an
      improved downstream processing of recombinant products. The Gram-positive
      bacterium Bacillus megaterium was used to secrete recombinant protein A fused to
      a histidine tag into the culture supernatant in shaker flasks. Superparamagnetic
      iron oxide nanoparticles functionalized with 3-glycidoxypropyl-trimethoxysilane
      coupled-nitrilotriacetic-acid groups (GNTA-SPION) were synthesized and added
      directly to the growing culture. After 10min incubation time, >85% of the product
      was adsorbed onto the particles. The particles were magnetically separated using
      handheld neodymium magnets and the product was eluted. The GNTA-SPION were
      successfully regenerated and reused in five consecutive cycles. In the one-step
      purification, the purity of the product reached >99.9% regarding protein A. A
      very low particle concentration of 0.5g/L was sufficient for effective product
      separation. Bacterial growth was not influenced negatively by this concentration.
      Particle analysis showed similar properties between freshly synthesized and
      regenerated GNTA-SPION. The overall process efficiency was however influenced by
      partial disintegration of particle agglomerates and thus loss of particles. The
      demonstration of very fast in situ product removal from growing bacterial culture
      combined with a very high product purity within one step shows possibilities for
      automated large scale purification combined with recycling of biomass.

PMID- 27888122
TI  - The sunflower transcription factor HaHB11 confers tolerance to water deficit and
      salinity to transgenic Arabidopsis and alfalfa plants.
AB  - Homeodomain-leucine zipper (HD-Zip) transcription factors are unique to the plant
      kingdom; members of subfamily I are known to be involved in abiotic stress
      responses. HaHB11 belongs to this subfamily and it was previously shown that it
      is able to confer improved yield and tolerance to flooding via a quiescent
      strategy. Here we show that HaHB11 expression is induced by ABA, NaCl and water
      deficit in sunflower seedlings and leaves. Arabidopsis transgenic plants
      expressing HaHB11, controlled either by its own promoter or by the constitutive
      35S CaMV, presented rolled leaves and longer roots than WT when grown under
      standard conditions. In addition, these plants showed wider stems and more
      vascular bundles. To deal with drought, HaHB11 transgenic plants closed their
      stomata faster and lost less water than controls, triggering an enhanced
      tolerance to such stress condition and also to salinity stress. Concomitantly,
      ABA-synthesis and sensing related genes were differentially regulated in HaHB11
      transgenic plants. Either under long-term salinity stress or mild drought stress,
      HaHB11 transgenic plants did not exhibit yield penalties. Moreover, alfalfa
      transgenic plants were generated which also showed enhanced drought tolerance.
      Altogether, the results indicated that HaHB11 was able to confer drought and
      salinity tolerance via a complex mechanism which involves morphological,
      physiological and molecular changes.

PMID- 27888120
TI  - Gestational exposure to perfluorooctanoic acid (PFOA): Alterations in motor
      related behaviors.
AB  - Perfluoroalkyl and polyfluoroalkyl substances are used in commercial applications
      and developmental exposure has been implicated in alterations in neurobehavioral
      functioning. While associations between developmental perfluorooctanoic acid
      (PFOA) exposure and human outcomes have been inconsistent, studies in
      experimental animals suggest alterations in motor related behaviors. To examine a
      dose-response pattern of neurobehavioral effects following gestational exposure
      to PFOA, pregnant CD-1 mice received PFOA (0, 0.1, 0.3, 1.0mg/kg/day) via oral
      gavage from gestational day 1-17 and the male offspring examined. Motor activity
      assessments on postnatal day (PND)18, 19, and 20 indicated a shift in the
      developmental pattern with an elevated activity level observed in the
      1.0mg/kg/day dose group on PND18. In the adult, no alterations were observed in
      body weights, activity levels, diurnal pattern of running wheel activity, startle
      response, or pre-pulse startle inhibition. In response to a subcutaneous
      injection of saline or nicotine (80MUg/kg), all animals displayed a transient
      increase in activity likely associated with handling with no differences observed
      across dose groups. Inhibition of motor activity over 18days of 400MUg/kg
      nicotine injection was not significantly different across dose groups.
      Hyperactivity induced by 2mg/kg (+)-methamphetamine hydrochloride intraperitoneal
      injection was significantly lower in the 1.0mg/kg/day PFOA dose group as compared
      to controls. Taken together, these data suggest that the effects on motor-related
      behaviors with gestational PFOA exposure do not mimic those reported for acute
      postnatal exposure. Changes were not observed at dose levels under 1.0mg/kg/day
      PFOA. Further examination of pathways associated with methamphetamine-induced
      activity is warranted.

PMID- 27888123
TI  - Acute rhinosinusitis during Hajj season 2014: Prevalence of bacterial infection
      and patterns of antimicrobial susceptibility.
AB  - BACKGROUND: The presence of large number of pilgrims during Hajj in Makkah region
      increases the risk of respiratory diseases. In this study, we aimed to assess the
      bacteriology of acute rhinosinusitis (ARS) during Hajj season and to demonstrate
      the antimicrobial susceptibility patterns that should guide the clinicians
      towards more appropriate antibiotic use. METHODS: Patients with ARS presenting
      during Hajj season of 2014 were prospectively enrolled. According to EPOS2012
      criteria. Sampling of sinus secretions was performed from the middle meatus
      adjacent to the maxillary sinus ostium via endoscopic guidance. Over all, the
      study has covered all ENT, emergency and outpatient departments in Hajj. RESULTS:
      Two hundred and twenty six patients with ARS were enrolled in the study.
      Pathogenic bacteria were identified in 93 (41.2%) patients. Of the 93 patients
      with bacterial ARS, Staphylococcus aureus was isolated in 46 (49.5%) patients,
      out of which 13 (28.3%) were methicillin-resistant Staphylococcus aureus
      (MRSA).The second most common group of bacterial isolates was Enterobacteriaceae
      such as Escherichia coli, and various Klebsiella species. Antibiotic sensitivity
      showed that methicillin-sensitive Staphylococcus aureus (MSSA) was also sensitive
      to cephalosporins, quinolones and clindamycin, while exhibiting relatively less
      sensitivity rates to amoxicillin-clavulinic acid and macrolides. CONCLUSION: Our
      study demonstrates the importance of assessing the bacteriology of ARS to help
      implement guidelines for proper treatment and prevention protocols during Hajj
      season.

PMID- 27888124
TI  - Is Adam of Cremona's 13th century paper "De regimine et via itineris" the first
      travel medicine guide?

PMID- 27888125
TI  - Initiating NTD programs targeting schistosomiasis and soil-transmitted
      helminthiasis in two provinces of the Democratic Republic of the Congo:
      Establishment of baseline prevalence for mass drug administration.
AB  - BACKGROUND: Schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) are
      widely distributed in the Democratic Republic of the Congo (DRC) and constitute a
      serious public health problem. As recommended by the World Health Organization
      (WHO), before launching mass chemotherapy to control these diseases,
      parasitological surveys were conducted in sentinel sites in six health zones
      (HZs) in Bandundu and Maniema provinces. Baseline prevalence and intensity of
      infection for SCH and STH were determined to establish the appropriate treatment
      plan using Praziquantel (PZQ) and Albendazole (ALB). METHODS: Parasitological
      surveys were conducted from April to May 2015 in twenty-six selected sampling
      units (schools) for baseline mapping in six HZs: Fifty school children (25
      females and 25 males) aged 9-15 years were randomly selected per sampling unit. A
      total of 1300 samples (urine and stool) were examined using haematuria dipsticks,
      parasite-egg filtration and the point-of-care Circulating Cathodic Antigen (POC
      CCA) assay for urine samples and the Kato-Katz technique for stool specimens.
      RESULTS: Three species of schistosomes (S. mansoni, S. haematobium and S.
      intercalatum) and three groups of STH (hookworm, Ascaris and Trichuris) were
      detected at variable prevalence and intensity among the schools, the HZs and the
      provinces. In Bandundu, no SCH was detected by either Kato-Katz or the POC-CCA
      technique, despite a high prevalence of STH with 68% and 80% at Kiri and Pendjua
      HZs, respectively. In Maniema, intestinal schistosomiasis was detected by both
      Kato-Katz and POC-CCA with an average prevalence by Kato-Katz of 32.8% and by POC
      CCA of 42.1%. Comparative studies confirmed the greater sensitivity (and
      operational feasibility) of the POC-CCA test on urine compared to Kato-Katz
      examination of stool for diagnosing intestinal schistosomiasis even in areas of
      comparatively light infections. STH was widely distributed and present in all HZs
      with a mean prevalence (95% CI) of 59.62% (46.00-65.00%). The prevalence of
      hookworm, roundworm and whipworm were 51.62% (32.40%-71.50%), 15.77% (0.50%
      39.60%) and 13.46 (0.50%-33.20%), respectively. CONCLUSION: This study provided
      the evidence base for implementing programs targeting SCH and STH in these Health
      Zones. Observations also reinforce the operational value and feasibility of the
      POC-CCA test to detect S. mansoni and, for the first time, S. intercalatum
      infections in a routine NTD program setting.

PMID- 27888126
TI  - Understanding the complex evolution of rapidly mutating viruses with deep
      sequencing: Beyond the analysis of viral diversity.
AB  - With the advent of affordable deep sequencing technologies, detection of low
      frequency variants within genetically diverse viral populations can now be
      achieved with unprecedented depth and efficiency. The high-resolution data
      provided by next generation sequencing technologies is currently recognised as
      the gold standard in estimation of viral diversity. In the analysis of rapidly
      mutating viruses, longitudinal deep sequencing datasets from viral genomes during
      individual infection episodes, as well as at the epidemiological level during
      outbreaks, now allow for more sophisticated analyses such as statistical
      estimates of the impact of complex mutation patterns on the evolution of the
      viral populations both within and between hosts. These analyses are revealing
      more accurate descriptions of the evolutionary dynamics that underpin the rapid
      adaptation of these viruses to the host response, and to drug therapies. This
      review assesses recent developments in methods and provide informative research
      examples using deep sequencing data generated from rapidly mutating viruses
      infecting humans, particularly hepatitis C virus (HCV), human immunodeficiency
      virus (HIV), Ebola virus and influenza virus, to understand the evolution of
      viral genomes and to explore the relationship between viral mutations and the
      host adaptive immune response. Finally, we discuss limitations in current
      technologies, and future directions that take advantage of publically available
      large deep sequencing datasets.

PMID- 27888127
TI  - Characterization of small interfering RNAs derived from Rice black streaked dwarf
      virus in infected maize plants by deep sequencing.
AB  - Rice black streaked dwarf virus (RBSDV) is the casual agent of maize rough dwarf
      disease, which frequently causes severe yield loss in China. However, the
      interaction between RBSDV and maize plants is largely unknown. RNA silencing is a
      conserved mechanism against viruses in plants. To understand the antiviral RNA
      interfering response in RBSDV-infected plants, the profile of virus-derived small
      interfering RNAs (vsiRNAs) from RBSDV in infected maize plants was obtained by
      deep sequencing in this study. Our data showed that vsiRNAs, accumulated
      preferentially as 21- and 22-nucleotide (nt) species, were mapped against all 10
      genomic RNA segments of RBSDV and derived almost equally overall from both
      positive and negative strands, while there were significant differences in the
      accumulation level of vsiRNAs from segments 2, 4, 6, 7 and 10. The vsiRNAs (21
      and 22 nt) generated from each segment of RBSDV genome had a 5'-terminal
      nucleotide bias toward adenine and uracil. The single-nucleotide resolution maps
      showed that RBSDV-derived siRNAs preferentially distributed in the 5'- or 3'
      terminal regions of several genomic segments. In addition, our results showed
      that the mRNA levels of some components involved in antiviral RNA silencing
      pathway were differentially modified during RBSDV infection. Among them, the
      accumulation levels of ZmDCL1, ZmDCL2, ZmDCL3a, ZmAGO1a, ZmAGO1b, ZmAGO2a,
      ZmAGO18a and ZmRDR6 mRNAs were significantly up-regulated, while those of
      ZmDCL3b, ZmDCL4 and ZmAGO1c mRNAs showed no obvious changes in RBSDV-infected
      maize plants.

PMID- 27888128
TI  - Neutrophil gelatinase-associated lipocalin production negatively correlates with
      HK-2 cell impairment: Evaluation of NGAL as a marker of toxicity in HK-2 cells.
AB  - Neutrophil gelatinase-associated lipocalin is an extracellular protein produced
      mostly in kidney. Recently, it has become a promising biomarker of renal damage
      in vivo. On the other hand, the validation of NGAL as a biomarker for
      nephrotoxicity estimation in vitro has not been characterized in detail yet.
      Since the HK-2 cells are frequently used human kidney cell line, we aimed to
      characterize the production of NGAL in these cells and to evaluate NGAL as a
      possible marker of cell impairment. We used heavy metals (mercury, cadmium),
      peroxide, drugs (acetaminophen, gentamicin) and cisplatin to mimic
      nephrotoxicity. HK-2 cells were incubated with selected compounds for 1-24h and
      cell viability was measured together with extracellular NGAL production. We
      proved that HK-2 cells possess a capacity to produce NGAL in amount of 2pg/ml/h.
      We found a change in cell viability after 24h incubation with all tested toxic
      compounds. The largest decrease of the viability was detected in mercury,
      acetaminophen, cisplatin and gentamicin. Unexpectedly, we found also a
      significant decrease in NGAL production in HK-2 cells treated with these toxins
      for 24h: to 11+/-5%, 54+/-5%, 57+/-6% and 76+/-9% respectively, compared with
      controls (=100%). Our results were followed with qPCR analysis when we found no
      significant increase in LCN2 gene expression after 24h incubation. We conclude
      that extracellular NGAL production negatively correlates with HK-2 cell
      impairment.

PMID- 27888129
TI  - Iron metabolism modulation in Atlantic salmon infested with the sea lice
      Lepeophtheirus salmonis and Caligus rogercresseyi: A matter of nutritional
      immunity?
AB  - Sea lice are copepodid ectoparasites that produce high economic losses and
      environmental issues, thus impacting the salmon aquaculture worldwide. Atlantic
      salmon (Salmo salar) from Northern and Southern Hemispheres are primarily
      parasitized by Lepeophtheirus salmonis and Caligus rogercresseyi, respectively.
      To cope L. salmonis infestation, studies suggest that Atlantic salmon can
      restrict iron availability as a mechanism of nutritional immunity. However, no
      molecular studies of iron regulation from salmonids infected with C.
      rogercresseyi have been reported. The aim of this study was to determine if there
      are differences in the regulation of iron metabolism in Atlantic salmon infested
      with L. salmonis or C. rogercresseyi. For comparisons, skin and head kidney were
      profiled using qPCR of 15 genes related to iron regulation in Atlantic salmons
      infected with each sea louse species in Norway and Chile, respectively. Prior to
      infestation, no significant differences were observed between fish group.
      However, genes involved in iron transport and Heme biosynthesis were highly
      upregulated in Atlantic salmon infested with L. salmonis. Interestingly, hepcidin
      and Heme oxygenase, a component of the Heme degradation pathway, were upregulated
      during C. rogercresseyi infestation. Oxidative stress related genes were also
      evaluated, showing higher transcription activity in the head kidney than in the
      skin of Atlantic salmon infested with L. salmonis. These comparative results
      suggest pathogen-specific responses in infected Atlantic salmon, where iron
      metabolism is primarily regulated during the infestation with L. salmonis than C.
      rogercresseyi. Feeding behavior, for instance haematophagy, of the infesting sea
      lice species in relation to iron modulation is discussed.

PMID- 27888130
TI  - Protective role of phenylalanine on the ROS-induced oxidative damage, apoptosis
      and tight junction damage via Nrf2, TOR and NF-kappaB signalling molecules in the
      gill of fish.
AB  - This study explored the possible preventive effects of dietary phenylalanine
      (Phe) on antioxidant responses, apoptosis and tight junction protein
      transcription in the gills of young grass carp (Ctenopharyngodon idella). Fish
      were fed six different experimental diets containing graded levels of Phe (3.4
      16.8 g kg-1) for 8 weeks. The results showed that Phe deficiency induced protein
      oxidation and lipid peroxidation by decreasing the glutathione content and the
      activities and mRNA levels of Cu/Zn superoxide dismutase (SOD1), catalase (CAT),
      glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S
      transferase (GST) in fish gill (P < 0.05). These results may be ascribed to the
      downregulation of NF-E2-related factor 2 (Nrf2), target of rapamycin (TOR) and
      ribosomal protein S6 kinase 1 (S6K1), and the upregulation of Kelch-like-ECH
      associated protein 1 a (Keap1a) expression in grass carp gills (P < 0.05).
      Additionally, Phe deficiency induced DNA fragmentation via the up-regulation of
      Caspase 3, Caspase 8 and Caspase 9 mRNA expression (P < 0.05). These results may
      be ascribed to the improvement in reactive oxygen species (ROS) levels in the
      fish gills (P < 0.05). Furthermore, the results indicated that Phe deficiency
      decreased Claudin b, Claudin 3, Occludin and ZO-1 transcription and increased
      Claudin 15 expression in the fish gills (P < 0.05). These effects were partly due
      to the downregulation of interleukin 10 (IL-10), transforming growth factor beta
      (TGF-beta) and inhibitor factor kappaBalpha (ikappaBalpha) and the upregulation
      of relative mRNA expression of interleukin 1beta (IL-1beta), interleukin 8 (IL
      8), tumour necrosis factor-alpha (TNF-alpha) and nuclear transcription factor
      kappaB p65 (NF-kappaB p65) (P < 0.05). Taken together, the results showed that
      Phe deficiency impaired the structural integrity of fish gills by regulating the
      expression of tight junction proteins, cytokines, antioxidant enzymes, NF-kappaB
      p65, ikappaBalpha, TOR, Nrf2, Keap1 and apoptosis-related genes in the fish
      gills.

PMID- 27888131
TI  - HSP70 and HSP90 are involved in shrimp Penaeus vannamei tolerance to AHPND
      causing strain of Vibrio parahaemolyticus after non-lethal heat shock.
AB  - Acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus
      carrying toxin-producing plasmid, has led to severe mortalities in farmed penaeid
      shrimp throughout Asia. Previous studies reported that a non-lethal heat shock
      (NLHS) could enhance disease tolerance in aquatic animals. Here, we investigate
      whether the NLHS could enhance the survival of shrimp Penaeusvannamei upon
      challenge with an AHPND-causing strain of V. Parahaemolyticus (VPAHPND). Two NLHS
      conditions, acute and chronic NLHSs, were used. The former abruptly exposed the
      juveniles shrimp from 28  degrees C to 38  degrees C for 30 min only once whereas
      the latter exposed the shrimp to 38  degrees C for 5 min every day for 7 days.
      The treated shrimp were, then, challenged with VPAHPND at day 3, day 7, and day
      30 during the recovery time after the treatment. The results showed that the
      shrimp exposed to either acute or chronic NLHS had higher survival rate (>50%)
      than that of the non-heated shrimp control (20%) when they were challenged with
      VPAHPND at day 3 recovery time. However, only those exposed to chronic NLHS
      showed the VPAHPND protection at day 7 and day 30 recovery times. Furthermore,
      the qRT-PCR analysis revealed that the expression of heat shock proteins,
      LvHSP70, LvHSP90 as well as other immune-related genes, LvproPO and LvCrustin,
      were induced upon exposure of shrimp to chronic NLHS. Interestingly, gene
      silencing of LvHSP70 and LvHSP90 eliminated the VPAHPND tolerance in the chronic
      NLHS shrimp and had decreasing PO activity suggesting that these LvHSPs played
      crucial roles in bacterial defense in shrimp. All together, we show for the first
      time that the NLHS enhance the shrimp tolerance to VPAHPND infection and this is
      likely mediated by the induction of LvHSP70, LvHSP90 and subsequent activation of
      the proPO system.

PMID- 27888132
TI  - Vitamin E deficiency depressed fish growth, disease resistance, and the immunity
      and structural integrity of immune organs in grass carp (Ctenopharyngodon
      idella): Referring to NF-kappaB, TOR and Nrf2 signaling.
AB  - This study investigated the effects of dietary vitamin E on growth, disease
      resistance and the immunity and structural integrity of head kidney, spleen and
      skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets
      containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet)
      for 10 weeks. Subsequently, a challenge test was conducted by injection of
      Aeromonas hydrophila. The results showed that compared with optimal vitamin E
      supplementation, vitamin E deficiency caused depressed growth, poor survival
      rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E
      deficiency decreased lysozyme and acid phosphatase activities, complement
      component 3 and complement component 4 contents in the head kidney, spleen and
      skin of grass carp (P < 0.05). Moreover, vitamin E deficiency down-regulated
      antimicrobial peptides (Hepcidin, liver-expressed antimicrobial peptide-2A, -2B,
      beta-defensin), IL-10, TGFbeta1, IkappaBalpha, TOR and S6K1 mRNA levels (P <
      0.05) and up-regulated IL-1beta, IL-6, IL-8, IFN-gamma2 and TNFalpha, NF-kappaB
      p65, IKKalpha, IKKbeta and 4EBP1 (not in the head kidney) mRNA levels (P < 0.05).
      In addition, vitamin E deficiency caused oxidative damage, decreased superoxide
      dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione
      reductase (GR) activities, and down-regulated the mRNA levels of antioxidant
      enzymes and signaling molecules Nrf2 (P < 0.05). Vitamin E deficiency also
      induced apoptosis by up-regulating capase-2, -3, -7, and -8 mRNA levels in the
      head kidney, spleen and skin of grass carp. In conclusion, this study indicated
      that dietary vitamin E deficiency depressed fish growth, impaired the immune
      function and disturbed the structural integrity of the head kidney, spleen and
      skin in grass carp, but optimal vitamin E supplementation can reverse those
      negative effects in fish. The optimal vitamin E requirements for young grass carp
      (266.39-1026.63 g) to achieve optimal growth performance and disease resistance
      based on the percent weight gain (PWG) and skin lesion morbidity were estimated
      to be 116.2 and 130.9 mg/kg diet, respectively. Meanwhile, based on immune
      indicator (LA activity in the head kidney) and antioxidant indicator (protection
      of spleen against MDA), the optimal vitamin E requirements for young grass carp
      were estimated to be 123.8 and 136.4 mg/kg diet, respectively.

PMID- 27888133
TI  - Network pharmacology-based study on the mechanism of action for herbal medicines
      in Alzheimer treatment.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD), as the most common type
      of dementia, has brought a heavy economic burden to healthcare system around the
      world. However, currently there is still lack of effective treatment for AD
      patients. Herbal medicines, featured as multiple herbs, ingredients and targets,
      have accumulated a great deal of valuable experience in treating AD although the
      exact molecular mechanisms are still unclear. MATERIALS AND METHODS: In this
      investigation, we proposed a network pharmacology-based method, which combined
      large-scale text-mining, drug-likeness filtering, target prediction and network
      analysis to decipher the mechanisms of action for the most widely studied
      medicinal herbs in AD treatment. RESULTS: The text mining of PubMed resulted in
      10 herbs exhibiting significant correlations with AD. Subsequently, after drug
      likeness filtering, 1016 compounds were remaining for 10 herbs, followed by
      structure clustering to sum up chemical scaffolds of herb ingredients. Based on
      target prediction results performed by our in-house protocol named AlzhCPI,
      compound-target (C-T) and target-pathway (T-P) networks were constructed to
      decipher the mechanism of action for anti-AD herbs. CONCLUSIONS: Overall, this
      approach provided a novel strategy to explore the mechanisms of herbal medicine
      from a holistic perspective.

PMID- 27888134
TI  - Perilla frutescens leaves extract ameliorates ultraviolet radiation-induced
      extracellular matrix damage in human dermal fibroblasts and hairless mice skin.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Perilla frutescens (L.) Britt. (Lamiaceae) is a
      traditional herb that is consumed in East Asian countries as a traditional
      medicine. This traditional herb has been documented for centuries to treat
      various diseases such as depression, allergies, inflammation and asthma. However,
      the effect of Perilla frutescens on skin has not been characterized well. AIM OF
      THE STUDY: The present study aimed to investigate the effect of Perilla
      frutescens leaves extract (PLE) on ultraviolet radiation-induced extracellular
      matrix damage in human dermal fibroblasts and hairless mice skin. MATERIALS AND
      METHODS: Human dermal fibroblasts and Skh-1 hairless mice were irradiated with UV
      and treated with PLE. Protein and mRNA levels of various target molecules were
      analyzed by western blotting and quantitative RT-PCR, respectively. Histological
      changes of mouse skin were analyzed by H&E staining. To elucidate underlying
      mechanism of PLE, activator protein-1 (AP-1) DNA binding assay and the
      measurement of reactive oxygen species (ROS) were performed. RESULTS: PLE
      significantly inhibited basal and UV-induced MMP-1 and MMP-3 expression dose
      dependently, and also decreased UV-induced phosphorylation of extracellular
      signal-regulated kinases and c-Jun N-terminal kinases. This inhibitory effects of
      PLE on MMP-1 and MMP-3 were mediated by reduction of ROS generation and AP-1 DNA
      binding activity induced by UV. Furthermore, PLE promoted type I procollagen
      production irrespective of UV irradiation. In the UV-irradiated animal model, PLE
      significantly reduced epidermal skin thickness and MMP-13 expression induced by
      UV. CONCLUSION: Our results demonstrate that PLE has the protective effect
      against UV-induced dermal matrix damage. Therefore, we suggest that PLE can be a
      potential agent for prevention of skin aging.

PMID- 27888135
TI  - Antihypertensive effects of androgens in conscious, spontaneously hypertensive
      rats.
AB  - Androgens are vasoactive steroids that induce acute vasodilation in a number of
      isolated vascular beds from different species, but the effects of these hormones
      on systemic blood pressure (BP) have been studied little. Although it has been
      reported that androgens exert systemic hypotensive effects through peripheral
      vasodilation in normotensive rats, there have not been any reports of systemic
      hypotensive effects of androgens in animals with hypertension. This study was
      designed to evaluate the acute effects of testosterone (TES) and its 5-reduced
      metabolites on systemic BP in hypertensive rats and to test the hypothesis that
      hypotestosteronemia may be involved in the pathogenesis of hypertension. Chronic,
      indwelling catheters were implanted in carotid artery and jugular vein of 18-21
      week-old male spontaneously hypertensive rats (SHR) and normotensive-control
      Wistar-Kyoto (WKY) rats, for BP recording and drug administration, respectively.
      Bolus injections of TES, 5alpha- or 5beta-dihydrotestosterone (5alpha- and 5beta
      DHT), were administrated cumulatively to conscious rats at doses of 0.1
      100MUmolkg-1min-1. 5beta-DHT was also administrated during the pressor effect of
      Bay K 8644, an L-type voltage-operated Ca2+ channel (L-VOCC) agonist. In separate
      experiments, BP of orchidectomized normotensive male WKY and Wistar rats, with or
      without androgen-replacement therapy, was evaluated weekly for 10 weeks by tail
      cuff plethysmography. TES and its metabolites reduced BP in a dose-dependent
      manner, while heart rate was reduced with some androgens at the highest doses.
      The hypotensive effects of androgens were markedly greater in SHR, with a rank
      order potency of: 5beta-DHT>TES>5alpha-DHT. 5beta-DHT, the most potent
      antihypertensive androgen, abolished the pressor response to Bay K 8644 in SHR.
      TES deprivation by orchidectomy increased BP in normotensive WKY and Wistar rats,
      but this hypertension was prevented by TES replacement therapy. BP responses to
      androgens are androgen structure-dependent. These data indicate that: 1)
      androgens play a significant role in the control of BP and may contribute to the
      pathogenesis of hypertension; 2) blockade of L-VOCC is involved in the
      antihypertensive effects of androgens, which are non-genomically mediated; and 3)
      hypotestosteronemia may be a risk factor for hypertension.

PMID- 27888136
TI  - Different epigenetic mechanisms of ERalpha implicated in the fate of fulvestrant
      resistant breast cancer.
AB  - Approximately 70% of breast cancers express estrogen receptor alpha (ERalpha),
      which plays critical roles in breast cancer development. Fulvestrant has been
      effectively used to treat ERalpha-positive breast cancer, although resistance
      remains a critical problem. To elucidate the mechanism of resistance to
      fulvestrant, we established fulvestrant-resistant cell-lines named MFR (MCF-7
      derived fulvestrant resistance) and TFR (T-47D derived fulvestrant resistance)
      from the ERalpha-positive luminal breast cancer cell lines MCF-7 and T-47D,
      respectively. Both fulvestrant-resistant cell lines lost sensitivity to estrogen
      and anti-estrogens. We observed diminished ERalpha expression at both the protein
      and mRNA levels. To address the mechanism of gene expression regulation, we
      examined epigenetic alteration, especially the DNA methylation level of ERalpha
      gene promoters. MFR cells displayed high methylation levels upstream of the
      ERalpha gene, whereas no change in DNA methylation was observed in TFR cells.
      Hence, we examined the gene expression plasticity of ERalpha, as there are
      differences in its reversibility following fulvestrant withdrawal. ERalpha gene
      expression was not restored in MFR cells, and alternative intracellular
      phosphorylation signals were activated. By contrast, TFR cells exhibited
      plasticity of ERalpha gene expression and ERalpha-dependent growth; moreover,
      these cells were resensitized to estrogen and anti-estrogens. The difference in
      epigenetic regulation among individual cells might explain the difference in the
      plasticity of ERalpha expression. We also identified an MFR cell-activating
      HER/Src-Akt/MAPK pathway; thus, the specific inhibitors effectively blocked MFR
      cell growth. This finding implies the presence of multiple fulvestrant resistance
      mechanisms and suggests that the optimal therapies differ among individual tumors
      as a result of differing epigenetic mechanisms regulating ERalpha gene
      expression.

PMID- 27888139
TI  - An improved agar medium for growth of Geobacillus thermoglucosidarius strains.
AB  - Geobacillus species have potential applications in many biotechnological
      processes. They are fastidious in their vitamin and amino acid requirements. A
      new semi-defined agar medium (SDM) was developed which gave consistently high
      viable cell counts of various G. thermoglucosidasius strains (5*108-6*108cfu/ml)
      under aerobic conditions at 70 degrees C.

PMID- 27888138
TI  - The quality of placebos used in randomized, controlled trials of lumbar and
      pelvic joint thrust manipulation-a systematic review.
AB  - BACKGROUND CONTEXT: Spinal manipulative therapy (SMT) has been attributed with
      substantial non-specific effects. Accurate assessment of the non-specific effects
      of SMT relies on high-quality studies with low risk of bias that compare with
      appropriate placebos. PURPOSE: This review aims to characterize the types and
      qualities of placebo control procedures used in controlled trials of manually
      applied, lumbar and pelvic (LP)-SMT, and to evaluate the assessment of subject
      blinding and expectations. STUDY DESIGN: This is a systematic review of
      randomized, placebo-controlled trials. METHODS: We searched MEDLINE, EMBASE,
      Cochrane Central Register of Controlled Trials, Index to Chiropractic Literature,
      and relevant bibliographies. We included randomized, placebo or sham-controlled
      trials where the index treatment was manually applied LP-SMT. There were no
      restrictions on the type of condition being investigated. Two independent
      reviewers selected the studies, assessed study quality, and extracted the data.
      Relevant data were the type and quality of placebo control(s) used, the
      assessment of blinding and expectations, and the results of those assessments.
      RESULTS: Twenty-five randomized, placebo-controlled trials were included in this
      review. There were 18 trials that used a sham manual SMT procedure for their
      placebo control intervention; the most common approach was with an SMT setup but
      without the application of any thrust. One small pilot study used an
      unequivocally indistinguishable placebo, two trials used placebos that had been
      validated as inert a priori, and eight trials reported on the success of subject
      blinding. Risk of bias was high or unclear, for all included studies.
      CONCLUSIONS: Imperfect placebos are ubiquitous in clinical trials of LP-SMT, and
      few trials have assessed for successful subject blinding or balanced expectations
      of treatment success between active and control group subjects. There is thus a
      strong potential for unmasking of control subjects, unequal non-specific effects
      between active and control groups, and non-inert placebos in existing trials.
      Future trials should consider assessing the success of subject blinding and
      ensuring inertness of their placebo a priori, as a minimum standard for quality.

PMID- 27888137
TI  - The role of RhoA in retrograde neuronal death and axon regeneration after spinal
      cord injury.
AB  - Paralysis following spinal cord injury (SCI) is due to interruption of axons and
      their failure to regenerate. It has been suggested that the small GTPase RhoA may
      be an intracellular signaling convergence point for several types of growth
      inhibiting extracellular molecules. Even if this is true in vitro, it is not
      clear from studies in mammalian SCI, whether the effects of RhoA manipulations on
      axon growth in vivo are due to a RhoA-mediated inhibition of true regeneration or
      only of collateral sprouting from spared axons, since work on SCI generally is
      performed with partial injury models. RhoA also has been implicated in local
      neuronal apoptosis after SCI, but whether this reflects an effect on axotomy
      induced cell death or an effect on other pathological mechanisms is not known. In
      order to resolve these ambiguities, we studied the effects of RhoA knockdown in
      the sea lamprey central nervous system (CNS), where after complete spinal cord
      transection (TX), robust but incomplete regeneration of large axons belonging to
      individually identified reticulospinal (RS) neurons occurs, and where some RS
      neurons show unambiguous delayed retrograde apoptosis after axotomy. RhoA protein
      was detected in neurons and axons of the lamprey brain and spinal cord, and its
      expression was increased post-TX. Knockdown of RhoA in vivo by retrogradely
      delivered morpholino antisense oligonucleotides (MOs) to the RS neurons
      significantly reduced retrograde apoptosis signaling in identified RS neurons
      post-SCI, as indicated by Fluorochrome Labeled Inhibitor of Caspases (FLICA) in
      brain wholemounts. In individual RS neurons, the reduction of caspase activation
      by RhoA knockdown began at 2weeks post-TX and was still seen at 8weeks. RhoA
      knockdown slowed axon retraction and possibly increased early axon regeneration
      in the proximal stump. The number of axons regenerating beyond the lesion more
      than 5mm at 10weeks post-TX also was increased. Thus RhoA knockdown both enhanced
      true axon regeneration and inhibited retrograde apoptosis signaling after SCI.

PMID- 27888140
TI  - Designed covalent allosteric modulators: an emerging paradigm in drug discovery.
AB  - Covalent allosteric modulators possess the pharmacological advantages (high
      potency, extended duration of action and low drug resistance) of covalent ligands
      and the additional benefit of the higher specificity and lower toxicity of
      allosteric modulators. This approach is gaining increasing recognition as a
      valuable tool in drug discovery. Here, we review the recent advances in the
      design of covalent allosteric modulators with an emphasis on successful examples.
      A broad spectrum of protein targets capable of being modulated by them reflects
      the prevalence of this strategy. We also discuss the challenges and future
      directions in the development of covalent allosteric modulators.

PMID- 27888141
TI  - A glimpse into the modulation of post-translational modifications of human
      colonizing bacteria.
AB  - Protein post-translational modifications (PTMs) are a key bacterial feature that
      holds the capability to modulate protein function and responses to environmental
      cues. Until recently, their role in the regulation of prokaryotic systems has
      been largely neglected. However, the latest developments in mass spectrometry
      based proteomics have allowed an unparalleled identification and quantification
      of proteins and peptides that undergo PTMs in bacteria, including in species
      which directly or indirectly affect human health. Herein, we address this issue
      by carrying out the largest and most comprehensive global pooling and comparison
      of PTM peptides and proteins from bacterial species performed to date. Data was
      collected from 91 studies relating to PTM bacterial peptides or proteins
      identified by mass spectrometry-based methods. The present analysis revealed that
      there was a considerable overlap between PTMs across species, especially between
      acetylation and other PTMs, particularly succinylation. Phylogenetically closer
      species may present more overlapping phosphoproteomes, but environmental triggers
      also contribute to this proximity. PTMs among bacteria were found to be extremely
      versatile and diverse, meaning that the same protein may undergo a wide variety
      of different modifications across several species, but it could also suffer
      different modifications within the same species.

PMID- 27888142
TI  - Profiling and identification of new proteins involved in brain ischemia using
      MALDI-imaging-mass-spectrometry.
AB  - : The identification of proteins involved in brain ischemia might allow the
      discovery of putative biomarkers or therapeutic targets for ischemic stroke. Our
      aim is to study the distribution of proteins within mouse brain after an ischemic
      insult using MALDI imaging-mass-spectrometry and to identify relevant proteins
      involved in brain damage. We occluded the middle cerebral artery of C57BL/6J
      mice. Brain slices were analyzed by MALDI-TOF and infarct (IC) and contralateral
      (CL) regions were compared using ClinProTools. The ion distribution maps of
      relevant m/z values were obtained by FlexImagin3.0. Protein identification was
      conducted through a bottom-up approach consisting on complementary sample
      fractionation methods. Some identifications were confirmed by
      immunohistochemistry and western blot. We identified 102 m/z values with
      different abundances between IC and CL (p<0.05), from which 21 m/z peaks were
      selected as more relevant. Thirteen of them were found increased in the infarct
      region and 4 m/z values showed AUC>90% between IC and CL. Identification analyses
      confirmed altered expressions of ATP5i, COX6C and UMP-CMP kinase in IC compared
      to CL. BIOLOGICAL SIGNIFICANCE: Using MALDI-IMS we identified for the first time
      new proteins that might be involved in brain ischemia representing potential
      diagnostic biomarkers or target molecules for neurological recovery.

PMID- 27888143
TI  - Dissolution behavior of co-amorphous amino acid-indomethacin mixtures: The
      ability of amino acids to stabilize the supersaturated state of indomethacin.
AB  - Arginine, phenylalanine, and tryptophan have been previously shown to improve the
      solid-state stability of amorphous indomethacin. The present study investigates
      the ability of these amino acids to prolong the supersaturation of indomethacin
      in both aqueous and biorelevant conditions either when freely in solution or when
      formulated as co-amorphous mixtures. The co-amorphous amino acid-indomethacin
      mixtures (molar ratio 1:1) and amorphous indomethacin were prepared by
      cryomilling. Dissolution and precipitation tests were performed in buffer
      solutions (pH 5 and 6.5) and in Fed and Fasted State Simulated Intestinal Fluids
      (FeSSIF and FaSSIF, respectively). Precipitation tests were conducted with the
      solvent shift method. The supersaturation stability of indomethacin and the
      precipitation inhibitory effect of amino acids were evaluated by calculating the
      supersaturation factor and the excipient gain factor, respectively. Biorelevant
      media exerted a significant effect on indomethacin solubility but had little
      effect on the supersaturation stability. Arginine had the most significant impact
      on the dissolution properties of indomethacin, but also phenylalanine and
      tryptophan stabilized supersaturation in some media when formulated as co
      amorphous mixtures with indomethacin. Only arginine stabilized supersaturation
      without co-amorphization, an effect only observed in media of pH 6.5. The unique
      behavior of the arginine-indomethacin mixture was further demonstrated by the
      abrupt formation of a precipitate, when an excess physical mixture of arginine
      and indomethacin was added to FeSSIF (pH 6.5). The solid-state investigation of
      this precipitate indicated that it probably consisted of crystalline arginine
      indomethacin salt with possibly some residual crystalline starting materials.

PMID- 27888144
TI  - Calcifediol-loaded liposomes for local treatment of pulmonary bacterial
      infections.
AB  - The influence of vitamin D3 and its metabolites calcifediol (25(OH)D) and
      calcitriol on immune regulation and inflammation is well described, and raises
      the question of potential benefit against bacterial infections. In the current
      study, 25(OH)D was encapsulated in liposomes to enable aerosolisation, and tested
      for the ability to prevent pulmonary infection by Pseudomonas aeruginosa.
      Prepared 25(OH)D-loaded liposomes were nanosized and monodisperse, with a
      negative surface charge and a 25(OH)D entrapment efficiency of approximately 23%.
      Jet nebulisation of liposomes was seen to yield an aerosol suitable for tracheo
      bronchial deposition. Interestingly, 25(OH)D in either liposomes or ethanolic
      solution had no effect on the release of the proinflammatory cytokine KC from
      Pseudomonas-infected murine epithelial cells (LA-4); treatment of infected, human
      bronchial 16-HBE cells with 25(OH)D liposomes however resulted in a significant
      reduction in bacterial survival. Together with the importance of selecting an
      application-appropriate in vitro model, the current study illustrates the
      feasibility and practicality of employing liposomes as a means to achieve 25(OH)D
      lung deposition. 25(OH)D-loaded liposomes further demonstrated promising effects
      regarding prevention of Pseudomonas infection in human bronchial epithelial
      cells.

PMID- 27888145
TI  - Critical role of hnRNP A1 in activating KRAS transcription in pancreatic cancer
      cells: A molecular mechanism involving G4 DNA.
AB  - KRAS is one of the most mutated genes in human cancer. Its crucial role in the
      tumourigenesis of pancreatic ductal adenocarcinoma (PDAC) has been widely
      demonstrated. As this deadly cancer does not sufficiently respond to conventional
      chemotherapies, it is important to increase our knowledge of pancreatic cancer
      biology, in particular how oncogenic KRAS is regulated. The promoter of KRAS
      contains a GA-element composed of runs of guanines that fold into a G4 structure.
      This unusual DNA conformation is recognized by several nuclear proteins,
      including MAZ and hnRNP A1. Recent data have revealed that KRAS is interconnected
      to ILK and hnRNP A1 in a circuitry that enables pancreatic cancer cells to
      maintain an aggressive phenotype. The present review illustrates recent advances
      on how KRAS is regulated in pancreatic cancer cells, focusing on the formation of
      G4 structures in the KRAS promoter and their interaction with hnRNP A1. The newly
      discovered KRAS-ILK-hnRNP A1 regulatory loop is discussed, emphasizing its
      potential as a therapeutic target for PDAC-specific molecules. This article is
      part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta
      Giancola and Dr. Daniela Montesarchio.

PMID- 27888146
TI  - A rhodium(III)-based inhibitor of autotaxin with antiproliferative activity.
AB  - BACKGROUND: Cancer of the skin is by far the most common of all cancers. Melanoma
      accounts for only about 1% of skin cancers but causes a large majority of skin
      cancer deaths. Autotaxin (ATX), also known as ectonucleotide
      pyrophosphatase/phosphodiesterase 2 (ENPP2), regulates physiological and
      pathological functions of lysophosphatidic acid (LPA), and is thus an important
      therapeutic target. METHODS: We synthesized ten metal-based complexes and a novel
      cyclometalated rhodium(III) complex 1 was identified as an ATX enzymatic
      inhibitor using multiple methods, including ATX enzymatic assay, thermal shift
      assay, western immunoblotting and so on. RESULTS: Protein thermal shift assays
      showed that 1 increased the melting temperature (Tm) of ATX by 3.5 degrees C. 1
      also reduced ATX-LPA mediated downstream survival signal pathway proteins such as
      ERK and AKT, and inhibited the activation of the transcription factor nuclear
      factor kappaB (NF-kappaB) and signal transducer and activator of transcription 3
      (STAT3). 1 also exhibited strong anti-proliferative activity against A2058
      melanoma cells (IC50=0.58MUM). Structure-activity relationship indicated that
      both the rhodium(III) center and the auxiliary ligands of complex 1 are important
      for bioactivity. CONCLUSIONS: 1 represents a promising scaffold for the
      development of small-molecule ATX inhibitors for anti-tumor applications. To our
      knowledge, complex 1 is the first metal-based ATX inhibitor reported to date.
      GENERAL SIGNIFICANCE: Rhodium complexes will have the increased attention in
      therapeutic and bioanalytical applications.

PMID- 27888147
TI  - Pathway analysis of complex diseases for GWAS, extending to consider rare
      variants, multi-omics and interactions.
AB  - BACKGROUND: Genome-wide association studies (GWAS) is a major method for studying
      the genetics of complex diseases. Finding all sequence variants to explain fully
      the aetiology of a disease is difficult because of their small effect sizes. To
      better explain disease mechanisms, pathway analysis is used to consolidate the
      effects of multiple variants, and hence increase the power of the study. While
      pathway analysis has previously been performed within GWAS only, it can now be
      extended to examining rare variants, other "-omics" and interaction data. SCOPE
      OF REVIEW: 1. Factors to consider in the choice of software for GWAS pathway
      analysis. 2. Examples of how pathway analysis is used to analyse rare variants,
      other "-omics" and interaction data. MAJOR CONCLUSIONS: To choose appropriate
      software tools, factors for consideration include covariate compatibility, null
      hypothesis, one- or two-step analysis required, curation method of gene sets,
      size of pathways, and size of flanking regions to define gene boundaries. For
      rare variants, analysis performance depends on consistency between assumed and
      actual effect distribution of variants. Integration of other "-omics" data and
      interaction can better explain gene functions. GENERAL SIGNIFICANCE: Pathway
      analysis methods will be more readily used for integration of multiple sources of
      data, and enable more accurate prediction of phenotypes.

PMID- 27888149
TI  - Testicular Spermatozoa Are of Better Quality Than Epididymal Spermatozoa in
      Patients With Obstructive Azoospermia.
AB  - OBJECTIVE: To assess sperm quality as a function of the sampling site (testis or
      epididymis) in obstructive azoospermia (OA). MATERIALS AND METHODS: DNA
      fragmentation rates in spermatozoa sampled from the testis and epididymis (from
      patients with different etiologies of OA) were assessed in a dUTP nick-end
      labeling assay. RESULTS: Twenty-one OA patients were included: 5 had congenital
      bilateral absence of the vas deferens, 8 had genital tract infections, and 8 had
      idiopathic OA. A total of 8506 spermatozoa sampled from the testis, 18,358
      sampled from the caput epididymis, and 18,881 sampled from the corpus/cauda
      epididymis were assessed. For each patient, spermatozoa from the testis had a
      lower overall DNA fragmentation rate (6.71% +/- 0.75 in average) than epididymal
      spermatozoa from the caput (14.86% +/- 1.89 in average; P = .0007) or the
      corpus/cauda (32.61% +/- 3.11 in average; P < .0001). The DNA fragmentation rates
      did not differ significantly as a function of the etiology of OA. In this small
      series, all deliveries were obtained with sperm samples with a low DNA
      fragmentation rate and delivery rates tended to be higher when testicular sperm
      (rather than epididymal sperm) was used (35.7% vs 12.1%, respectively; P = .06).
      CONCLUSION: Our data argue in favor of using testicular sperm (rather than
      epididymal sperm) for patients with obstructive azoospermia.

PMID- 27888148
TI  - A Pilot Study of a Multimodal Treatment Paradigm to Accelerate Drug Evaluations
      in Early-stage Metastatic Prostate Cancer.
AB  - OBJECTIVE: To evaluate a multimodal strategy aimed at treating all sites of
      disease that provides a rapid readout of success or failure in men presenting
      with non-castrate metastatic prostate cancers that are incurable with single
      modality therapy. MATERIALS AND METHODS: Twenty selected men with oligometastatic
      M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated
      using a multimodal approach that included androgen deprivation, radical
      prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the
      presence of clinically positive retroperitoneal nodes), and stereotactic body
      radiotherapy to osseous disease or the primary site. Outcomes of each treatment
      were assessed sequentially. Androgen deprivation was discontinued in responding
      patients. The primary end point was an undetectable prostate-specific antigen
      (PSA) after testosterone recovery. The goal was to eliminate all detectable
      disease. RESULTS: Each treatment modality contributed to the outcome: 95% of the
      cohort achieved an undetectable PSA with multimodal treatment, including 25% of
      patients after androgen deprivation alone and an additional 50% and 20% after
      surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence
      interval: 3%-38%) achieved the primary end point, which persisted for 5, 6, 27+ ,
      and 46+ months. All patients meeting the primary end point had been classified
      with M1b disease at presentation. CONCLUSION: A sequentially applied multimodal
      treatment strategy can eliminate detectable disease in selected patients with
      metastatic spread at diagnosis. The end point of undetectable PSA after
      testosterone recovery should be considered when evaluating new approaches to
      rapidly set priorities for large-scale testing in early metastatic disease states
      and to shift the paradigm from palliation to cure.

PMID- 27888150
TI  - Coenzyme Q10 Intake From Food and Semen Parameters in a Subfertile Population.
AB  - OBJECTIVE: To assess the association between coenzyme Q10 (CoQ10) intake from
      food sources and semen quality. We assessed this association in a prospective
      cohort of men attending a fertility clinic. CoQ10 supplementation has been
      associated with improvements in semen parameters. However, the impact of CoQ10
      intake from food sources on semen quality has not been investigated. MATERIALS
      AND METHODS: Subfertile couples seeking fertility evaluation at the Massachusetts
      General Hospital Fertility Center were invited to participate in an ongoing study
      of environmental factors and fertility. In total, 211 male participants completed
      a validated food frequency questionnaire and provided 476 semen samples.
      Multivariable linear mixed models were used to examine the relation between CoQ10
      intake from food and semen parameters while adjusting for potential confounders
      and accounting for within-person correlations. RESULTS: Mean dietary CoQ10 intake
      was 19.2 mg/day (2.4-247.2 mg/day). No subjects were taking CoQ10 supplements.
      There were no associations between dietary CoQ10 intake from food and
      conventional semen parameters. The adjusted mean difference (95% confidence
      interval) comparing men in the top and bottom quartiles of CoQ10 intake from food
      were -3.1 mil/mL (95% confidence interval -29.5, 38.8 mil/mL) for sperm
      concentration, -4.5% (-15.1%, 6.0%) for total motility, -1.3% for progressive
      motility (-8.4%, 5.7%), and 0.3% (-1.4%, 2.0%) for sperm morphology. CONCLUSION:
      CoQ10 intake from food was not related to semen parameters among subfertile men.
      Mean dietary intake of CoQ10 in this study was 10-fold lower than the
      supplemental dose used in clinical trials showing improved sperm motility. CoQ10
      intake from food alone may be insufficient to optimize semen parameters.

PMID- 27888151
TI  - Examining Pediatric Cases From the Clinical Research Office of the Endourological
      Society Ureteroscopy Global Study.
AB  - OBJECTIVE: To evaluate the characteristics and outcomes of ureteroscopy (URS) in
      children treated in several hospitals participating in the Clinical Research
      Office of the Endourological Society (CROES) Study, and to present the overall
      results of pediatric URS compared with adults. PATIENTS AND METHODS: The CROES
      Study collected data on consecutive patients treated with URS for urolithiasis at
      each participating center over a 1-year period. The collected prospective global
      database includes data for 11,885 patients who received URS at 114 centers in 32
      countries. Of these URS-treated patients, 192 were <=18 years old. RESULTS: Of
      the 114 centers participating in the study, 42% had conducted pediatric URS.
      Among the pediatric cases, 7 were infants, 53 were small children, 59 were school
      aged children, and 73 were adolescents. A considerable number (37%) of the
      pediatric cases had previously undergone URS treatment. No differences in the
      surgical outcomes of the adults and children were reported. The URS-treated
      children had a greater number of positive preoperative urine cultures when
      compared with adult cases treated. A semirigid scope was used in the vast
      majority of pediatric cases (85%). According to the present data, within the
      group of URS-treated children, the younger the child, the more readmissions
      occurred. CONCLUSION: URS is as efficient and safe in children as it is in
      adults. The data suggest that readmissions among URS-treated children are
      associated with age, with the likelihood of readmissions greater among younger
      age groups.

PMID- 27888152
TI  - An Improved Methodology to Overcome Key Issues in Human Fecal Metagenomic DNA
      Extraction.
AB  - Microbes are ubiquitously distributed in nature, and recent culture-independent
      studies have highlighted the significance of gut microbiota in human health and
      disease. Fecal DNA is the primary source for the majority of human gut microbiome
      studies. However, further improvement is needed to obtain fecal metagenomic DNA
      with sufficient amount and good quality but low host genomic DNA contamination.
      In the current study, we demonstrate a quick, robust, unbiased, and cost
      effective method for the isolation of high molecular weight (>23kb) metagenomic
      DNA (260/280 ratio >1.8) with a good yield (55.8+/-3.8ng/mg of feces). We also
      confirm that there is very low human genomic DNA contamination (eubacterial:
      human genomic DNA marker genes=227.9:1) in the human feces. The newly-developed
      method robustly performs for fresh as well as stored fecal samples as
      demonstrated by 16S rRNA gene sequencing using 454 FLX+. Moreover, 16S rRNA gene
      analysis indicated that compared to other DNA extraction methods tested, the
      fecal metagenomic DNA isolated with current methodology retains species richness
      and does not show microbial diversity biases, which is further confirmed by qPCR
      with a known quantity of spike-in genomes. Overall, our data highlight a protocol
      with a balance between quality, amount, user-friendliness, and cost effectiveness
      for its suitability toward usage for culture-independent analysis of the human
      gut microbiome, which provides a robust solution to overcome key issues
      associated with fecal metagenomic DNA isolation in human gut microbiome studies.

PMID- 27888153
TI  - Three-dimensional black-blood T2 mapping with compressed sensing and data-driven
      parallel imaging in the carotid artery.
AB  - PURPOSE: To develop a 3D black-blood T2 mapping sequence with a combination of
      compressed sensing (CS) and parallel imaging (PI) for carotid wall imaging.
      MATERIALS AND METHODS: A 3D black-blood fast-spin-echo (FSE) sequence for T2
      mapping with CS and PI was developed and validated. Phantom experiments were
      performed to assess T2 accuracy using a Eurospin Test Object, with different
      combination of CS and PI acceleration factors. A 2D multi-echo FSE sequence was
      used as a reference to evaluate the accuracy. The concordance correlation
      coefficient and Bland-Altman statistics were calculated. Twelve volunteers were
      scanned twice to determine the repeatability of the sequence and the intraclass
      correlation coefficient (ICC) was reported. Wall-lumen sharpness was calculated
      for different CS and PI combinations. Six patients with carotid stenosis >50%
      were scanned with optimised sequence. The T2 maps were compared with multi
      contrast images. RESULTS: Phantom scans showed good correlation in T2 measurement
      between current and reference sequence (r=0.991). No significant difference was
      found between different combination of CS and PI accelerations (p=0.999).
      Volunteer scans showed good repeatability of T2 measurement (ICC: 0.93, 95% CI
      0.84-0.97). The mean T2 of the healthy wall was 48.0+/-9.5ms. Overall plaque T2
      values from patients were 54.9+/-12.2ms. Recent intraplaque haemorrhage and
      fibrous tissue have higher T2 values than the mean plaque T2 values (88.1+/-6.8ms
      and 62.7+/-9.3ms, respectively). CONCLUSION: This study demonstrates the
      feasibility of combining CS and PI for accelerating 3D T2 mapping in the carotid
      artery, with accurate T2 measurements and good repeatability.

PMID- 27888155
TI  - Significant HLA class I type associations with aromatic antiepileptic drug (AED)
      induced SJS/TEN are different from those found for the same AED-induced DRESS in
      the Spanish population.
AB  - Aromatic antiepileptic drugs (AEDs) are among the drugs most frequently involved
      in severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome
      (SJS), toxic epidermal necrolysis (TEN), and drug reactions with eosinophilia and
      systemic symptoms (DRESS). This study investigated the associations between the
      genetic polymorphisms of HLA class-I and AED-induced SCARs in the Spanish
      population. HLA class-I genotypes were determined in AED
      (phenytoin[PHT],lamotrigine[LTG],carbamazepine[CBZ],phenobarbital[PB])-induced
      SJS/TEN (n=15) or DRESS (n=12) cases included in the Spanish SCAR registry,
      PIELenRed. There were 3 control groups: (A)tolerant to a single AED, (B)tolerant
      to any AED, and (C)Spanish population controls. For SJS/TEN, concomitant HLA
      A*02:01/Cw15:02 alleles were significantly associated with PHT-cases compared to
      control groups B and C [(B)odds ratio(OR):14.75, p=0.009;(C)OR:27.50, p<0.001],
      and were close to significance with respect to control group A (p=0.060). The
      genotype frequency of the HLA-B*38:01 was significantly associated with PHT-LTG
      cases compared with the 3 groups of controls [(A)OR:12.86, p=0.012;(B)OR:13.81;
      p=0.002;(C)OR:14.35, p<0.001], and with LTG-cases [(A)OR:147.00,
      p=0.001;(B)OR:115.00, p<0.001;(C)OR:124.70, p<0.001]. We found the HLA-B*15:02
      allele in a Spanish Romani patient with a CBZ-case. The HLA-A*11:01 was
      significantly associated with CBZ-cases [(A)OR:63.89, p=0.002;(B)OR:36.33,
      p=0.005;(C)OR:28.29, p=0.007]. For DRESS, the HLA-A*24:02 genotype frequency was
      statistically significant in the PHT-LTG-cases [(A)OR:22.56, p=0.003;(B)OR:23.50.
      p=0.001; (C)OR:33.25, p<0.001], and in the LTG-cases [(A),OR:49.00,
      p=0.015;(B)OR:27.77, p=0.005; (C)OR:34.53, p=0.002]. HLA-A*31:01 was
      significantly associated with the CBZ-cases [(A)OR:22.00, p=0.047;(B)OR:29.50,
      p=0.033;(C)OR:35.14, p=0.006]. In conclusion, we identified several significant
      genetic risk factors for the first time in the Spanish Caucasian population: HLA
      A*02:01/Cw*15:02 combination as a risk factor for PHT-induced SJS/TEN, HLA
      B*38:01 for LTG- and PHT- induced SJS/TEN, HLA-A*11:01 for CBZ-induced SJS/TEN,
      and HLA-A*24:02 for LTG- and PHT- induced DRESS. The strong association between
      HLA*31:01 and CBZ-DRESS in Europeans was confirmed in this study.

PMID- 27888156
TI  - Effects of pomegranate juice on blood pressure: A systematic review and meta
      analysis of randomized controlled trials.
AB  - Punica granatum L. (Pomegranate) has been claimed to provide several health
      benefits. Pomegranate juice is a polyphenol-rich fruit juice with high
      antioxidant capacity. Several studies suggested that pomegranate juice can exert
      antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory effects.
      Nevertheless, the potential cardioprotective benefits of pomegranate juice
      deserve further clinical investigation. To systematically review and meta-analyze
      available evidence from randomized placebo-controlled trials (RCTs) investigating
      the effects of pomegranate juice consumption and blood pressure (BP). A
      comprehensive literature search in Medline and Scopus was carried out to identify
      eligible RCTs. A meta-analysis of eligible studies was performed using a random
      effects model. Quality assessment, sensitivity analysisand publication bias
      evaluations were conducted using standard methods. Quantitative data synthesis
      from 8 RCTs showed significant reductions in both systolic [weighed mean
      difference (WMD): -4.96mmHg, 95% CI: -7.67 to -2.25, p<0.001) and diastolic BP
      (WMD: -2.01mmHg, 95% CI: -3.71 to -0.31, p=0.021) after pomegranate juice
      consumption. Effects on SBP remained stable to sensitivity analyses. Pomegranate
      juice reduced SBP regardless of the duration (>12 wks: WMD=-4.36mmHg, 95% CI: 
      7.89 to -0.82, p=0.016) and <12 wks: WMD=-5.83 mmHg, 95% CI: -10.05 to -1.61,
      p=0.007) and dose consumed (>240cc: WMD=-3.62mmHg, 95% CI: -6.62 to -0.63,
      p=0.018) and <240cc: WMD=-11.01mmHg, 95% CI: -17.38 to -4.65, p=0.001,
      pomegranate juice per day) whereas doses >240cc provided a borderline significant
      effect in reducing DBP. The present meta-analysis suggests consistent benefits of
      pomegranate juice consumption on BP. This evidence suggests it may be prudent to
      include this fruit juice in a heart-healthy diet.

PMID- 27888157
TI  - Curcumin use in pulmonary diseases: State of the art and future perspectives.
AB  - Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric
      (Curcuma longa). It has been used for centuries in Ayurveda (Indian traditional
      medicine) for the treatment of several diseases. Over the last several decades,
      the therapeutic properties of curcumin have slowly been elucidated. It has been
      shown that curcumin has pleiotropic effects, regulating transcription factors
      (e.g., NF-kB), cytokines (e.g., IL6, TNF-alpha), adhesion molecules (e.g., ICAM
      1), and enzymes (e.g., MMPs) that play a major role in inflammation and
      cancerogenesis. These effects may be relevant for several pulmonary diseases that
      are characterized by abnormal inflammatory responses, such as asthma or chronic
      obstructive pulmonary disease, acute respiratory distress syndrome, pulmonary
      fibrosis, and acute lung injury. Furthermore, some preliminary evidence suggests
      that curcumin may have a role in the treatment of lung cancer. The evidence for
      the use of curcumin in pulmonary disease is still sparse and has mostly been
      obtained using either in vitro or animal models. The most important issue with
      the use of curcumin in humans is its poor bioavailability, which makes it
      necessary to use adjuvants or curcumin nanoparticles or liposomes. The aim of
      this review is to summarize the available evidence on curcumin's effectiveness in
      pulmonary diseases, including lung cancer, and to provide our perspective on
      future research with curcumin so as to improve its pharmacological effects, as
      well as provide additional evidence of curcumin's efficacy in the treatment of
      pulmonary diseases.

PMID- 27888158
TI  - Metabolomic profile of children with recurrent respiratory infections.
AB  - Recurrent respiratory infections (RRI) represent a widespread condition which has
      a severe social and economic impact. Immunostimulants are used for their
      prevention. It is crucial to better characterize children with RRI to refine
      their diagnosis and identify effective personalized prevention strategies.
      Metabolomics is a high-dimensional biological method that can be used for
      hypothesis-free biomarker profiling, examining a large number of metabolites in a
      given sample using spectroscopic techniques. Multivariate statistical data
      analysis then enables us to infer which metabolic information is relevant to the
      biological characterization of a given physiological or pathological condition.
      This can lead to the emergence of new, sometimes unexpected metabolites, and
      hitherto unknown metabolic pathways, enabling the formulation of new pathogenetic
      hypotheses, and the identification of new therapeutic targets. The aim of our
      pilot study was to apply mass-spectrometry-based metabolomics to the analysis of
      urine samples from children with RRI, comparing these children's biochemical
      metabolic profiles with those of healthy peers. We also compared the RRI
      children's and healthy controls' metabolomic urinary profiles after the former
      had received pidotimod treatment for 3 months to see whether this immunostimulant
      was associated with biochemical changes in the RRI children's metabolic profile.
      13 children (age range 3-6 yeas) with RRI and 15 matched per age healthy peers
      with no history of respiratory diseases or allergies were enrolled. Their
      metabolomic urine samples were compared before and after the RRI children had
      been treated with pidotimod for a period of 3 months. Metabolomic analyses on the
      urine samples were done using mass spectrometry combined with ultra-performance
      liquid chromatography (UPLC-MS). The resulting spectroscopic data then underwent
      multivariate statistical analysis and the most relevant variables characterizing
      the two groups were identified. Data modeling with post-transformation of PLS2
      Discriminant Analysis (ptPLS2-DA) generated a robust model capable of
      discriminating the urine samples from children with RRI from those of healthy
      controls (R2=0.92,Q2CV7-fold=0.75, p-value<0.001). The dataset included 1502 time
      per mass variables, and 138 of them characterized the difference between the two
      groups. Thirty-five of these distinctive 138 variables persisted in the profiles
      of the children with RRI after pidotimod treatment. Metabolomics can discriminate
      children with RRI from healthy controls, suggesting that the former have a
      dysregulated metabolic profile. Among the variables characterizing children with
      RRI there are metabolites that may reflect the presence of a different
      microbiome. After pidotimod treatment, the metabolic profile of the children with
      RRI was no longer very different from that of the healthy controls, except for
      the persistence of some microbiome-related variables. We surmise that pidotimod
      partially "restores" the altered metabolic profile of children with RRI, without
      modifying the metabolites related to the composition of the gut microbiota. In
      the light of these results, we hypothesize a potential synergic effect of the
      combined use of immunostimulants and probiotics for the purpose of prevention in
      children with RRI.

PMID- 27888154
TI  - Modulation of VEGF receptor 2 signaling by protein phosphatases.
AB  - Phosphorylation of serines, threonines, and tyrosines is a central event in
      signal transduction cascades in eukaryotic cells. The phosphorylation state of
      any particular protein reflects a balance of activity between kinases and
      phosphatases. Kinase biology has been exhaustively studied and is reasonably well
      understood, however, much less is known about phosphatases. A large body of
      evidence now shows that protein phosphatases do not behave as indiscriminate
      signal terminators, but can function both as negative or positive regulators of
      specific signaling pathways. Genetic models have also shown that different
      protein phosphatases play precise biological roles in health and disease.
      Finally, genome sequencing has unveiled the existence of many protein
      phosphatases and associated regulatory subunits comparable in number to kinases.
      A wide variety of roles for protein phosphatase roles have been recently
      described in the context of cancer, diabetes, hereditary disorders and other
      diseases. In particular, there have been several recent advances in our
      understanding of phosphatases involved in regulation of vascular endothelial
      growth factor receptor 2 (VEGFR2) signaling. The receptor is the principal
      signaling molecule mediating a wide spectrum of VEGF signal and, thus, is of
      paramount significance in a wide variety of diseases ranging from cancer to
      cardiovascular to ophthalmic. This review focuses on the current knowledge about
      protein phosphatases' regulation of VEGFR2 signaling and how these enzymes can
      modulate its biological effects.

PMID- 27888159
TI  - Transmembrane TNF-alpha reverse signaling leading to TGF-beta production is
      selectively activated by TNF targeting molecules: Therapeutic implications.
AB  - Tumor necrosis factor (TNF)-alpha is a potent pro-inflammatory cytokine exerting
      pleiotropic effects on various cell types. It is synthesized in a precursor form
      called transmembrane TNF-alpha (mTNF-alpha) which, after being processed by
      metalloproteinases, is released in a soluble form to mediate its biological
      activities through Type 1 and 2 TNF receptors in TNF receptor expressing cells.
      In addition to acting in soluble form, TNF-alpha also acts in the transmembrane
      form both as a ligand by activating TNF receptors, as well as a receptor that
      transmits outside-to-inside (reverse) signals back into mTNF-alpha bearing cells.
      Since the discovery that TNF-alpha plays a determining role in the pathogenesis
      of several chronic inflammatory diseases, anti-TNF agents are increasingly being
      used in the treatment of a rapidly expanding number of rheumatic and systemic
      autoimmune diseases, such as rheumatoid arthritis, Crohn's disease, psoriasis,
      psoriatic arthritis, ankyloting spondylitis, Wegener granulomatosis and
      sarcoidosis. There are 5 TNF antagonists currently available: etanercept, a
      soluble TNF receptor construct; infliximab, a chimeric monoclonal antibody;
      adalimumab and golimumab, fully human antibodies; and certolizumab pegol, an Fab'
      fragment of a humanized anti-TNF-alpha antibody. Though each compound can
      efficiently neutralize TNF-alpha, increasing evidence suggests that they show
      different efficacy in the treatment of these diseases. These observations
      indicate that in addition to neutralizing TNF-alpha, other biological effects
      induced by TNF-alpha targeting molecules dictate the success of the therapy.
      Recently, we found that mTNF-alpha reverse signaling leads to transforming growth
      factor (TGF)-beta production in macrophages and anti-TNF agents selectively
      trigger this pathway. In this review we will focus on the potential contribution
      of the activation of the mTNF-alpha signaling pathway to the success of the anti
      TNF therapy.

PMID- 27888160
TI  - Preliminary results of comparative study for subsequent photodynamic therapy
      versus secondary excision after primary excision for treating basal cell
      carcinoma.
AB  - Some basal cell carcinomas (BCCs) are indistinguishable from nevi based on
      clinical manifestations. Therefore, it is often difficult for the excision
      margins of the initial surgical treatment to achieve radical removal of the
      malignancy. This study was a comparative analysis of the clinical results of
      aminolevulinic acid (ALA)-photodynamic therapy (PDT) or secondary surgery after
      the primary excision. In total, 20 patients with preoperative clinical diagnoses
      of nevi underwent in situ resection. The postoperative pathological diagnoses
      confirmed all cases were BCC. Ten patients received PDT twice after the primary
      excision, and 10 cases received extended resection after the primary excision.
      Patients were followed up for 8 months at least, and the 2 groups did not show
      statistically significant differences in the recurrence rate, while the PDT group
      had better results in terms of economic burden, healing period, and cosmetic
      satisfaction than the group with secondary surgery. Our study demonstrates that
      ALA-PDT can sever as a considerable remedial treatment for the BCC patients who
      have not accepted radical resection due to primary clinical misdiagnosis.

PMID- 27888161
TI  - Sensitization of immune cells following hexylaminolevulinate photodynamic therapy
      of cervical intraepithelial neoplasia.
AB  - BACKGROUND: Effects of photodynamic therapy (PDT) were tested with respect to
      immune cell stimulation in cervical intraepithelial neoplasia (CIN). METHODS: A
      patient with CIN received hexaminolevulinate (HAL) and subsequent PDT. These data
      were compared to a placebo PDT patient and a healthy HPV16-vaccinated donor.
      Isolation of peripheral blood mononuclear cells (PBMC) was performed before PDT
      and at 4 different time points after PDT. The proliferation of these PBMC was
      tested by [3H]thymidine incorporation following stimulation with control or HPV16
      L1 peptides. Potential effects on the CD4+ and CD8+ cell subsets were analysed.
      RESULTS: The data revealed an unchanged or decreased proliferation of HPV16-L1
      peptide-stimulated PBMC as compared to placebo patient. HPV16-L1 peptide
      incubation of PBMC from the HAL patient demonstrated significant proliferative
      capacity after PDT. The CD4+ and CD8+ T cell populations in placebo patient were
      slightly increased after HPV16-L1 peptide administration at each time point.
      Mixed results were obtained for CD4+ cells as compared to controls and nearly
      unchanged amounts of CD8+ cells were detectable following HPV16-L1 peptide
      exposure of PBMC from the HAL/PDT-treated patient. CONCLUSIONS: These findings
      suggest a T cell reaction from CIN patients during repeated HAL/PDT treatment.
      However, further immune cell populations might be involved during PDT.

PMID- 27888162
TI  - Photodynamic therapy as an alternative treatment for relapsed or refractory
      mycosis fungoides: A systemic review.
AB  - Mycosis fungoides is the most common cutaneous T-cell lymphoma. It is
      characterized by slow progress over years to decades, developing from patches to
      infiltrated plaques, and sometimes to tumors. Therapies such as localized
      chemotherapy, photochemotherapy and radiotherapy are often employed when lesions
      of refractory or relapsing mycosis fungoides are resistant to conventional
      therapies. However, these methods have acute or chronic side effects and
      toxicity, which may accumulate with repeated and protracted treatment cycles.
      Photodynamic therapy is a promising, well-tolerated option for the treatment of
      localized lesions with excellent cosmetic outcomes. In this article, we
      systematically reviewed and discussed clinical application of photodynamic
      therapy in relapsed or refractory mycosis fungoides. There are 20 papers included
      in this review article.

PMID- 27888163
TI  - Antimicrobial photodynamic therapy adjuvant to non-surgical periodontal therapy
      in patients with diabetes mellitus: A meta-analysis.
AB  - BACKGROUND: To determine whether treatment with antimicrobial photodynamic
      therapy (aPDT) as an adjunct to scaling and root planing (SRP) improves
      periodontal clinical and glycemic outcomes in chronic periodontitis patients (CP)
      with type 2 diabetes mellitus (DM). METHODS: Databases (MEDLINE via PubMed;
      EMBASE; Cochrane Central Register of Controlled Trials and Cochrane Oral Health
      Group Trials Register databases) were searched up to and including October 2016.
      The addressed PICO question was: "What are the effects of aPDT as an adjunct to
      SRP in terms of periodontal and glycemic outcomes as compared to SRP alone in
      individuals with DM?" RESULTS: Four randomized clinical trials were included in
      the present review. All studies reporting clinical periodontal and metabolic
      parameters, showed that aPDT was effective in the treatment of CP in DM subjects
      at follow up. Considering the effects of aPDT as an adjunct as compared to SRP
      alone on clinical signs of CP in DM subjects, no difference could be observed for
      all evaluated parameters (PD: Z=-0.61, P=0.54; CAL: Z=0.27, P=0.78; HbA1c:
      Z=0.138, P=0.89) CONCLUSION: It remains debatable whether aPDT is effective as an
      adjunct to SRP than SRP alone in patients having CP with DM, given that the
      scientific evidence is weak. In terms of periodontal parameters and glycemic
      levels, aPDT does not provide additional benefit in the treatment of CP in DM
      patients. However, further randomized clinical trials with standard laser
      parameters and long follow up periods are warranted to study periodontal and
      glycemic outcomes in this regard.

PMID- 27888164
TI  - Optimizing Zn porphyrin-based photosensitizers for efficient antibacterial
      photodynamic therapy.
AB  - INTRODUCTION: Efficient photodynamic inactivation of microbes requires highly
      efficient photosensitizers which kill microbial cells, but spare host tissues.
      One way to achieve such selectivity is to use photosensitizers that are rapidly
      taken up by microbes and, when applied at low concentrations, efficiently kill
      them after a short illumination. Design of such photosensitizers requires insight
      into molecular properties which are critical for antimicrobial photo-efficiency.
      This study explores the contribution of molecular shape and exposure of charges,
      to the antimicrobial activity of tetra-cationic Zn porphyrin-based
      photosensitizers. MATERIALS AND METHODS: Two isomers, ortho (2) and meta (3)
      hexyl and octyl Zn(II) meso-tetrakis(N-alkylpyridinium-2(3)-yl)porphyrins
      [ZnTnHex-2(3)-PyP and ZnTnOct-2(3)-PyP] were compared for uptake and photo
      efficiency against a Gram-negative bacterium, Escherichia coli. RESULTS: The
      highest photo-efficiency was displayed by the meta hexyl derivative. At
      concentration as low as 1.0MUM and during only 5min of preincubation with the
      cells, ZnTnHex-3-PyP decreased viable cell number by about 6log10 after only 5min
      of illumination. Since bacterial suspensions were thoroughly washed after
      preincubation with photosensitizers, this effect can be attributed only to
      photosensitizer taken up or bound to E. coli. Irrespective of its highest uptake
      by the cells, the octyl meta isomer, ZnTnOct-3-PyP, did not show higher
      antibacterial activity than the shorter-chain hexyl derivative, ZnTnHex-3-PyP.
      CONCLUSION: Efficiency and eventually selectivity of antimicrobial
      photosensitizers can be improved by optimizing the shape of the molecule and the
      position of electric charges. Increasing lipophilicity and cellular uptake per
      se, does not necessarily materialize in high antimicrobial efficiency of the
      photosensitizer.

PMID- 27888165
TI  - Clinical effectiveness of adjunctive antimicrobial photodynamic therapy for
      residual pockets during supportive periodontal therapy: A systematic review and
      meta-analysis.
AB  - PURPOSE: To evaluate the clinical efficacy of antimicrobial photodynamic therapy
      (aPDT) adjunctive to scaling and root planing (SRP) in the treatment of residual
      pockets for chronic periodontitis patients on supportive periodontal therapy
      (SPT). METHOD: Bibliographic databases of MEDLINE and Cochrane Library were
      thoroughly searched up to July 2016 for eligible randomized controlled trials
      (RCTs). Mean differences (MD) and the corresponding 95% confidence intervals (CI)
      were synthesized for probing depth (PD) reduction and clinical attachment level
      (CAL) gain. The I2 test and Q statistics were employed to assess inter-study
      heterogeneity. Subgroup analysis was performed based on the enrollment of
      smokers. RESULT: Four RCTs fulfilling the eligibility criteria were included.
      Pooled estimates demonstrated statistically significant improvements in both PD
      reduction (MD=0.69, CI: 0.11-1.28, p=0.02) and CAL gain (MD=0.60, CI: 0.11-1.10,
      p=0.02) for SRP+aPDT versus SRP alone. Meta-analysis of studies with smokers
      failed to produce a significant additional effect in PD (MD=0.32, CI: -0.30 to
      0.94, p=0.31) and CAL (MD=0.42, CI: -0.26 to 1.09, p=0.23) when SRP was
      associated with aPDT. However, significant enhancements in PD reduction (MD=1.23,
      CI: 0.74-1.72, p<0.001) and CAL gain (MD=0.96, CI: 0.31-1.62, p=0.004) were
      observed for studies excluding smokers. CONCLUSION: Pooled evidence indicates an
      additional clinical improvement in the maintenance of residual pockets in favor
      of SRP+aPDT compared with SRP alone. Subgroup analysis demonstrates an adverse
      impact of smoking on clinical effect of the combined therapy. Substantial
      heterogeneity and the paucity of included studies undermine the statistical power
      of this meta-analysis. Future well-designed and large-scale clinical trials
      evaluating the adjunctive efficacy of aPDT in periodontal maintenance phase are
      critically needed.

PMID- 27888166
TI  - Positive Peer-Pressured Productivity (P-QUAD): Novel Use of Increased
      Transparency and a Weighted Lottery to Increase a Division's Academic Output.
AB  - OBJECTIVE: Evaluate a dual incentive model combining positive peer pressure
      through increased transparency of peers' academic work with a weighted lottery
      where entries are earned based on degree of productivity. METHODS: We developed a
      dual-incentive peer mentoring model, Positive Peer-Pressured Productivity (P
      QUAD), for faculty in the Pediatric Hospital Medicine Division at the University
      of Minnesota Masonic Children's Hospital. This model provided relative value
      based incentives, with points assigned to different scholarly activities (eg. 1
      point for abstract submission, 2 points for poster presentation, 3 points for
      oral presentation, etc.). These points translated into to lottery tickets for a
      semi-annual drawing for monetary prizes. Productivity was compared among faculty
      for P-QUAD year to the preintervention year. RESULTS: Fifteen (83%) of 18
      eligible faculty members participated. Overall annual productivity per faculty
      member as measured by total P-QUAD score increased from a median of 3
      (interquartile range [IQR] 0-14) in the preintervention year to 4 (IQR 0-27) in
      the P-QUAD year (P = .051). Submissions and acceptances increased in all
      categories except posters which were unchanged. Annual abstract submissions per
      faculty member significantly increased from a median of 1 (IQR 0-2) to 2 (IQR 0
      2; P = .047). Seventy-three percent (8 of 11) of post-survey respondents
      indicated that the financial incentive motivated them to submit academic work;
      100% indicated that increased awareness of their peers' work was a motivator.
      CONCLUSIONS: The combination of increased awareness of peers' academic
      productivity and a weighted lottery financial incentive appears to be a useful
      model for stimulating academic productivity in early-career faculty.

PMID- 27888168
TI  - Estimating the Duration of Public Concern After the Fukushima Dai-ichi Nuclear
      Power Station Accident From the Occurrence of Radiation Exposure-Related Terms on
      Twitter: A Retrospective Data Analysis.
AB  - BACKGROUND: After the Fukushima Dai-ichi Nuclear Power Station accident in Japan
      on March 11, 2011, a large number of comments, both positive and negative, were
      posted on social media. OBJECTIVE: The objective of this study was to clarify the
      characteristics of the trend in the number of tweets posted on Twitter, and to
      estimate how long public concern regarding the accident continued. We surveyed
      the attenuation period of the first term occurrence related to radiation exposure
      as a surrogate endpoint for the duration of concern. METHODS: We retrieved
      18,891,284 tweets from Twitter data between March 11, 2011 and March 10, 2012,
      containing 143 variables in Japanese. We selected radiation, radioactive, Sievert
      (Sv), Becquerel (Bq), and gray (Gy) as keywords to estimate the attenuation
      period of public concern regarding radiation exposure. These data, formatted as
      comma-separated values, were transferred into a Statistical Analysis System (SAS)
      dataset for analysis, and survival analysis methodology was followed using the
      SAS LIFETEST procedure. This study was approved by the institutional review board
      of Hokkaido University and informed consent was waived. RESULTS: A Kaplan-Meier
      curve was used to show the rate of Twitter users posting a message after the
      accident that included one or more of the keywords. The term Sv occurred in
      tweets up to one year after the first tweet. Among the Twitter users studied,
      75.32% (880,108/1,168,542) tweeted the word radioactive and 9.20%
      (107,522/1,168,542) tweeted the term Sv. The first reduction was observed within
      the first 7 days after March 11, 2011. The means and standard errors (SEs) of the
      duration from the first tweet on March 11, 2011 were 31.9 days (SE 0.096) for
      radioactive and 300.6 days (SE 0.181) for Sv. These keywords were still being
      used at the end of the study period. The mean attenuation period for radioactive
      was one month, and approximately one year for radiation and radiation units. The
      difference in mean duration between the keywords was attributed to the effect of
      mass media. Regularly posted messages, such as daily radiation dose reports, were
      relatively easy to detect from their time and formatted contents. The survival
      estimation indicated that public concern about the nuclear power plant accident
      remained after one year. CONCLUSIONS: Although the simple plot of the number of
      tweets did not show clear results, we estimated the mean attenuation period as
      approximately one month for the keyword radioactive, and found that the keywords
      were still being used in posts at the end of the study period. Further research
      is required to quantify the effect of other phrases in social media data. The
      results of this exploratory study should advance progress in influencing and
      quantifying the communication of risk.

PMID- 27888169
TI  - Impact of Information Technology-Based Interventions for Type 2 Diabetes Mellitus
      on Glycemic Control: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Information technology-based interventions are increasingly being
      used to manage health care. However, there is conflicting evidence regarding
      whether these interventions improve outcomes in people with type 2 diabetes.
      OBJECTIVE: The objective of this study was to conduct a systematic review and
      meta-analysis of clinical trials, assessing the impact of information technology
      on changes in the levels of hemoglobin A1c (HbA1c) and mapping the interventions
      with chronic care model (CCM) elements. METHODS: Electronic databases PubMed and
      EMBASE were searched to identify relevant studies that were published up until
      July 2016, a method that was supplemented by identifying articles from the
      references of the articles already selected using the electronic search tools.
      The study search and selection were performed by independent reviewers. Of the
      1082 articles retrieved, 32 trials (focusing on a total of 40,454 patients) were
      included. A random-effects model was applied to estimate the pooled results.
      RESULTS: Information technology-based interventions were associated with a
      statistically significant reduction in HbA1c levels (mean difference -0.33%, 95%
      CI -0.40 to -0.26, P<.001). Studies focusing on electronic self-management
      systems demonstrated the largest reduction in HbA1c (0.50%), followed by those
      with electronic medical records (0.17%), an electronic decision support system
      (0.15%), and a diabetes registry (0.05%). In addition, the more CCM-incorporated
      the information technology-based interventions were, the more improvements there
      were in HbA1c levels. CONCLUSIONS: Information technology strategies combined
      with the other elements of chronic care models are associated with improved
      glycemic control in people with diabetes. No clinically relevant impact was
      observed on low-density lipoprotein levels and blood pressure, but there was
      evidence that the cost of care was lower.

PMID- 27888170
TI  - A Predictive Model for Medical Events Based on Contextual Embedding of Temporal
      Sequences.
AB  - BACKGROUND: Medical concepts are inherently ambiguous and error-prone due to
      human fallibility, which makes it hard for them to be fully used by classical
      machine learning methods (eg, for tasks like early stage disease prediction).
      OBJECTIVE: Our work was to create a new machine-friendly representation that
      resembles the semantics of medical concepts. We then developed a sequential
      predictive model for medical events based on this new representation. METHODS: We
      developed novel contextual embedding techniques to combine different medical
      events (eg, diagnoses, prescriptions, and labs tests). Each medical event is
      converted into a numerical vector that resembles its "semantics," via which the
      similarity between medical events can be easily measured. We developed simple and
      effective predictive models based on these vectors to predict novel diagnoses.
      RESULTS: We evaluated our sequential prediction model (and standard learning
      methods) in estimating the risk of potential diseases based on our contextual
      embedding representation. Our model achieved an area under the receiver operating
      characteristic (ROC) curve (AUC) of 0.79 on chronic systolic heart failure and an
      average AUC of 0.67 (over the 80 most common diagnoses) using the Medical
      Information Mart for Intensive Care III (MIMIC-III) dataset. CONCLUSIONS: We
      propose a general early prognosis predictor for 80 different diagnoses. Our
      method computes numeric representation for each medical event to uncover the
      potential meaning of those events. Our results demonstrate the efficiency of the
      proposed method, which will benefit patients and physicians by offering more
      accurate diagnosis.

PMID- 27888167
TI  - Delta-Notch signalling in segmentation.
AB  - Modular body organization is found widely across multicellular organisms, and
      some of them form repetitive modular structures via the process of segmentation.
      It's vastly interesting to understand how these regularly repeated structures are
      robustly generated from the underlying noise in biomolecular interactions. Recent
      studies from arthropods reveal similarities in segmentation mechanisms with
      vertebrates, and raise the possibility that the three phylogenetic clades,
      annelids, arthropods and chordates, might share homology in this process from a
      bilaterian ancestor. Here, we discuss vertebrate segmentation with particular
      emphasis on the role of the Notch intercellular signalling pathway. We introduce
      vertebrate segmentation and Notch signalling, pointing out historical milestones,
      then describe existing models for the Notch pathway in the synchronization of
      noisy neighbouring oscillators, and a new role in the modulation of gene
      expression wave patterns. We ask what functions Notch signalling may have in
      arthropod segmentation and explore the relationship between Notch-mediated
      lateral inhibition and synchronization. Finally, we propose open questions and
      technical challenges to guide future investigations into Notch signalling in
      segmentation.

PMID- 27888172
TI  - Disease activity trajectories in early axial spondyloarthritis: results from the
      DESIR cohort.
AB  - BACKGROUND: Disease activity may change over time in axial spondyloarthritis
      (axSpA). The objectives were to identify patterns of disease activity evolution
      in patients with early axSpA. METHODS: Patients from the prospective early axSpA
      cohort (DEvenir des Spondyloarthrites Indifferenciees Recentes (DESIR)) who
      fulfilled the Assessment in SpondyloArthritis Society (ASAS) criteria for axSpA
      at baseline and with at least three Ankylosing Spondylitis Disease Activity Score
      (ASDAS) values available over the 3 years of follow-up were analysed. Statistical
      analyses: trajectories were estimated by group-based trajectory modelling;
      predisposing baseline factors for such trajectories were identified by univariate
      and multivariable multinomial (logit) regression; work disability over time was
      compared between the trajectories by Cox hazard model. RESULTS: In all, 370
      patients were analysed: mean disease duration was 1.6 (+/-0.9) years. The five
      distinct trajectories of disease activity over the 3 years were (t1) 'persistent
      moderate disease activity' (n=134 (36.2%)); (t2) 'persistent inactive disease'
      (n=66 (17.8%); (t3) 'changing from very high disease activity to inactive
      disease' ((n=29 (7.8%)); (t4) 'persistent high disease activity' (n=126 (34.1%))
      and (t5) 'persistent very high disease activity' (n=15 (4.1%)). After adjustment
      for other characteristics, t2 was associated with a white-collar job (OR=2.6 (95%
      CI 1.0 to 6.7)) and t3 with male gender (OR=7.1 (1.6 to 32.2)), higher education
      level (OR=9.4 (1.4 to 63.4)) and peripheral joint involvement (OR=6.2 (1.23 to
      31.32)). Patients from (t4) and (t5) were more often declared work disabled over
      follow-up (HR=5.2 (1.5 to 18.0) and HR=8.0 (1.3 to 47.9), respectively).
      CONCLUSIONS: Trajectory modelling of disease activity was feasible in early
      axSpA: more than 30% patients (141/370) were in a trajectory with a persistent
      high disease activity. Persistent high disease activity trajectories were
      significantly associated with consequences on work. TRIAL REGISTRATION NUMBER:
      NCT01648907.

PMID- 27888173
TI  - Association between job stress and occupational injuries among Korean
      firefighters: a nationwide cross-sectional study.
AB  - OBJECTIVE: We aimed to assess the nature of association between job stress and
      occupational injuries among firefighters in Korea. DESIGN: Cross-sectional study.
      SETTING: We conducted a nationwide survey using self-reported questionnaires in
      South Korea. PARTICIPANTS: A survey was conducted among 30 630 firefighters; 25
      616 (83.6%) responded. Our study included firefighters who were 20-59 years old.
      Individuals with <12 months of current job experience and those with missing data
      were excluded; ultimately, 14 991 firefighters were analysed. RESULTS: Among fire
      suppression personnel, high job demands (OR=1.49, 95% CI 1.25 to 1.77), high
      interpersonal conflicts (OR=1.18, 95% CI 1.02 to 1.37), a poor organisational
      system (OR=1.33, 95% CI 1.14 to 1.55), and a negative workplace environment
      (OR=1.41, 95% CI 1.21 to 1.64) were associated with the occurrence of
      occupational injury; high job demands (OR=1.22, 95% CI 1.01 to 1.47) were also
      associated with the frequency of injuries. Among emergency medical services
      personnel, high job demands (OR=1.26, 95% CI 1.03 to 1.54), high interpersonal
      conflicts (OR=1.40, 95% CI 1.19 to 1.66), a poor organisational system (OR=1.55,
      95% CI 1.30 to 1.85), lack of reward (OR=1.43, 95% CI 1.21 to 1.69) and a
      negative workplace environment (OR=1.30, 95% CI 1.10 to 1.54) were associated
      with the occurrence of occupational injury; low job control (OR=1.20, 95% CI 1.04
      to 1.38), high interpersonal conflicts (OR=1.18, 95% CI 1.03 to 1.36), lack of
      reward (OR=1.17, 95% CI 1.02 to 1.35) and a negative workplace climate (OR=1.16,
      95% CI 1.01 to 1.34) were also associated with a greater number of injuries.
      Among officers, high job demands (OR=1.96, 95% CI 1.35 to 2.85) and a negative
      workplace environment (OR=1.54, 95% CI 1.13 to 2.10) were associated with the
      occurrence of occupational injuries; however, there was no significant
      correlation between job stress and the number of injuries. CONCLUSIONS: High job
      stress among firefighters was associated with both the occurrence of occupational
      injury, and also with an increased frequency of injuries. Therefore, job stress
      should be addressed to prevent occupational injuries among firefighters.

PMID- 27888171
TI  - Clinical Relevance of the First Domomedicine Platform Securing Multidrug
      Chronotherapy Delivery in Metastatic Cancer Patients at Home: The inCASA European
      Project.
AB  - BACKGROUND: Telehealth solutions can improve the safety of ambulatory
      chemotherapy, contributing to the maintenance of patients at their home, hence
      improving their well-being, all the while reducing health care costs. There is,
      however, need for a practicable multilevel monitoring solution, encompassing
      relevant outputs involved in the pathophysiology of chemotherapy-induced
      toxicity. Domomedicine embraces the delivery of complex care and medical
      procedures at the patient's home based on modern technologies, and thus it offers
      an integrated approach for increasing the safety of cancer patients on
      chemotherapy. OBJECTIVE: The objective was to evaluate patient compliance and
      clinical relevance of a novel integrated multiparametric telemonitoring
      domomedicine platform in cancer patients receiving multidrug chemotherapy at
      home. METHODS: Self-measured body weight, self-rated symptoms using the 19-item
      MD Anderson Symptom Inventory (MDASI), and circadian rest-activity rhythm
      recording with a wrist accelerometer (actigraph) were transmitted daily by
      patients to a server via the Internet, using a dedicated platform installed at
      home. Daily body weight changes, individual MDASI scores, and relative percentage
      of activity in-bed versus out-of-bed (I<O) were computed. Chemotherapy was
      administered according to the patient medical condition. Compliance was evaluated
      according to the proportions of (1) patient-days with all data available (full)
      and (2) patient-days with at least one parameter available (minimal).
      Acceptability was assessed using the Whole Systems Demonstrator Service User
      Technology Acceptability Questionnaire. Linear discriminant analysis was used to
      identify the combination of parameters associated with subsequent unplanned
      hospitalization. RESULTS: A total of 31 patients (males: 55% [17/31]; World
      Health Organization Performance Status=0: 29% (9/31); age range: 35-91 years)
      participated for a median of 58 days (38-313). They received a total of 102
      chemotherapy courses (64.7% as outpatients). Overall full compliance was 59.7%
      (522/874), with at least one data available for 830/874 patient-days (95.0%),
      during the 30-day per-protocol span. Missing data rates were similar for each
      parameter. Patients were altogether satisfied with the use of the platform. Ten
      toxicity-related hospitalizations occurred in 6 patients. The combination of
      weighted circadian function (actigraphy parameter I<O), body weight change, and
      MDASI scores predicted for ensuing emergency hospitalization within 3 days, with
      an accuracy of 94%. CONCLUSIONS: Multidimensional daily telemonitoring of body
      weight, circadian rest-activity rhythm, and patient-reported symptoms was
      feasible, satisfactory, and clinically relevant in patients on chemotherapy. This
      domomedicine platform constitutes a unique tool for the further development of
      safe home-based chemotherapy administration.

PMID- 27888174
TI  - Phenotypic and antibiogram pattern of V. cholerae isolates from a tertiary care
      hospital in Mumbai during 2004-2013: a retrospective cross-sectional study.
AB  - OBJECTIVES: Cholera is a major gastroenteric disease with reports on fluctuation
      and resistance. Hence, the objective is to determine the trend in seasonality,
      resistance pattern, prevalent biotypes, serotypes and phage types between 2004
      and 2013 among Vibrio cholerae isolates. DESIGN: A retrospective cross-sectional
      study. SETTINGS: A single-centre study was carried out at a tertiary care
      hospital in a metropolitan city (Mumbai) of a developing country (India).
      METHODS: Records of stool specimen cultures of patients with suspected cholera
      from January 2004 to December 2013 were analysed. The organisms were identified
      as per standard protocol. Antimicrobial susceptibility testing was performed as
      per Clinical Laboratory Standard Institute. Biotyping, serotyping and phage
      typing were carried out. From the confirmed cases of cholera, demographic and
      laboratory details were noted. Descriptive analysis was used and the data were
      presented in the form of percentages. RESULTS: Vibrio cholerae was predominant in
      males and was isolated from 9.41% (439/4664) of stool specimens. Variability was
      found in terms of the gross appearance of stool specimens, seasonal trend and
      antibiotic resistance pattern. The antimicrobial susceptibility showed a waxing
      and waning pattern for most of the antibiotics (ampicillin, cefuroxime,
      chloramphenicol, tetracycline) tested, while for a few others the strains were
      either uniformly sensitive (gentamicin, norfloxacin) or resistant (trimethoprim
      sulfamethoxazole, nalidixic acid). All isolates belonged to subgroup O1 and
      biotype El Tor. The most common serotype was Ogawa. The predominant phage type
      was T2 (old scheme) and T27 (new scheme). CONCLUSIONS: The predominant biotype,
      serotype and phage type were El Tor, Ogawa and T27 phage, respectively. The
      changing trends in antimicrobial resistance pattern over the years necessitate
      continued epidemiological and microbiological surveillance of the disease.

PMID- 27888176
TI  - Nailfold capillary morphological characteristics of hand-arm vibration syndrome:
      a cross-sectional study.
AB  - OBJECTIVE: The purpose of this study was to investigate the characteristics of
      nailfold capillaroscopy associated with hand-arm vibration syndrome (HAVS).
      METHODS: In total, 113 male gold miners were recruited: 35 workers who were
      chronically exposed to vibration and developed vibration-induced white finger
      were defined as the HAVS group, 39 workers who were exposed to vibration but did
      not have HAVS were classified as the vibration-exposed controls (VEC) group, and
      39 workers without vibration exposure were categorised as the non-VEC (NVEC)
      group. Video capillaroscopy was used to capture images of the 2nd, 3rd and 4th
      fingers of both hands. The following nailfold capillary characteristics were
      included: number of capillaries/mm, avascular areas, haemorrhages and enlarged
      capillaries. The experiments were carried out in the same winter. All
      characteristics were evaluated under blinded conditions. RESULTS: Significant
      differences in all morphological characteristics existed between the groups
      (p<0.05). Avascular areas in the HAVS, VEC and NVEC groups appeared in 74.3%,
      43.6% and 25.0% of participants, respectively. A higher percentage of
      participants had haemorrhages in the HAVS group (65.7%) compared with the other
      groups (VEC: 7.7% and NVEC: 7.5%). The number of capillaries/mm, input limb
      width, output limb width, apical width, and ratio of output limb and input limb
      all had more than 70% sensitivity or specificity of their cut-off value.
      CONCLUSIONS: Nailfold capillary characteristics, especially the number of
      capillaries/mm, avascular areas, haemorrhages, output limb width, input limb
      width and apical width alterations, revealed significant associations with HAVS.

PMID- 27888175
TI  - Association between adolescent tobacco, alcohol and illicit drug use and
      individual and environmental resilience protective factors.
AB  - OBJECTIVES: Research suggests that individual and environmental resilience
      protective factors may be associated with adolescent substance use; however, the
      associations between a broad range of such factors and use of various types of
      substances have not been examined. The study aimed to determine the association
      between a comprehensive range of adolescent individual and environmental
      resilience protective factors and measures of tobacco, alcohol and illicit
      substance use. DESIGN: Cross-sectional study. SETTING: 32 Australian secondary
      schools. PARTICIPANTS: Grade 7-10 students (aged 11-17 years). MEASURES: Data
      regarding 14 student individual and environmental resilience protective factors
      and seven substance use measures (tobacco, alcohol, marijuana, other illicit drug
      use) were obtained via an online self-report survey. Adjusted multivariate
      logistic regression analyses examined the association between all student
      resilience protective factors and seven substance use measures. RESULTS: Inverse
      univariate associations were found for 94 of 98 relationships examined (n=10
      092). Multivariate analyses found: consistent inverse associations between 2 of
      14 protective factors and all substance use measures ('goals and aspirations',
      'prosocial peers'); inverse associations between 4 protective factors with
      multiple substance use measures ('home support' (5 of 7), 'school support' (3 of
      7), 'self-awareness' (2 of 7), 'community meaningful participation' (2 of 7));
      positive associations between 2 resilience protective factors with multiple
      measures of substance use ('community support' (3 of 7), 'peer caring
      relationships' (5 of 7)) and 6 protective factors not to be associated with any
      substance use measure. CONCLUSIONS: Despite individual relationships between the
      majority of resilience protective factors and substance use types, the protective
      benefit of such factors for adolescent substance use was limited to only a small
      number of such factors when considered collectively. Such results suggest that
      interventions seeking to reduce adolescent substance use may need to target
      specific protective factors to address specific types of substance use. TRIAL
      REGISTRATION NUMBER: ACTRN12611000606987, Results.

PMID- 27888177
TI  - Study protocol for a cluster-randomised controlled trial of an NCD access to
      medicines initiative: evaluation of Novartis Access in Kenya.
AB  - INTRODUCTION: Novartis recently launched Novartis Access, an initiative to
      provide a basket of reduced price medicines for non-communicable diseases (NCDs)
      to be sold through the public and private non-profit sectors in programme
      countries. This study will evaluate the impact of Novartis Access on the
      availability and price of NCD medicines at health facilities and households in
      Kenya, the first country to receive the programme. METHODS AND ANALYSIS: This
      study will be a cluster-randomised controlled trial. 8 counties in Kenya will be
      randomly assigned to the intervention or control group using a covariate
      constrained randomisation method to maximise balance on demographic and health
      characteristics. In intervention counties, public and private non-profit health
      facilities will be able to order Novartis Access NCD medicines from the Mission
      for Essential Drugs and Supplies (MEDS). Data will be collected from a random
      sample of 384 health facilities and 800 households at baseline, midline after 1
      year of intervention, and end-line after 2 years. Quarterly surveillance data
      will also be collected from health facilities and a subsample of households
      through phone-based interviews. Households will be eligible if at least one
      resident has been previously diagnosed and prescribed a medicine for an NCD
      addressed by Novartis Access, including hypertension and diabetes. The primary
      outcomes will be availability and price of NCD medicines at health facilities,
      and availability, price, and expenditures on NCD medicines at households. Impacts
      will be estimated using intention-to-treat analysis. ETHICS AND DISSEMINATION:
      This protocol was approved by the Institutional Review Boards at Strathmore
      University and at Boston University. Informed consent will be obtained from all
      participants at the start of the trial. The findings of the trial will be
      disseminated through peer-reviewed journals, international conferences, and
      meetings and events organised with local stakeholders. TRIAL REGISTRATION NUMBER:
      NCT02773095.

PMID- 27888178
TI  - Perceived causes of differential attainment in UK postgraduate medical training:
      a national qualitative study.
AB  - OBJECTIVES: Explore trainee doctors' experiences of postgraduate training and
      perceptions of fairness in relation to ethnicity and country of primary medical
      qualification. DESIGN: Qualitative semistructured focus group and interview
      study. SETTING: Postgraduate training in England (London, Yorkshire and Humber,
      Kent Surrey and Sussex) and Wales. PARTICIPANTS: 137 participants (96 trainees,
      41 trainers) were purposively sampled from a framework comprising: doctors from
      all stages of training in general practice, medicine, obstetrics and gynaecology,
      psychiatry, radiology, surgery or foundation, in 4 geographical areas, from white
      and black and minority ethnic (BME) backgrounds, who qualified in the UK and
      abroad. RESULTS: Most trainees described difficult experiences, but BME UK
      graduates (UKGs) and international medical graduates (IMGs) could face additional
      difficulties that affected their learning and performance. Relationships with
      senior doctors were crucial to learning but bias was perceived to make these
      relationships more problematic for BME UKGs and IMGs. IMGs also had to deal with
      cultural differences and lack of trust from seniors, often looking to IMG peers
      for support instead. Workplace-based assessment and recruitment were considered
      vulnerable to bias whereas examinations were typically considered more rigorous.
      In a system where success in recruitment and assessments determines where in the
      country you can get a job, and where work-life balance is often poor, UK BME and
      international graduates in our sample were more likely to face separation from
      family and support outside of work, and reported more stress, anxiety or burnout
      that hindered their learning and performance. A culture in which difficulties are
      a sign of weakness made seeking support and additional training stigmatising.
      CONCLUSIONS: BME UKGs and IMGs can face additional difficulties in training which
      may impede learning and performance. Non-stigmatising interventions should focus
      on trainee-trainer relationships at work and organisational changes to improve
      trainees' ability to seek social support outside work.

PMID- 27888179
TI  - Predicting tuberculosis risk in the foreign-born population of British Columbia,
      Canada: study protocol for a retrospective population-based cohort study.
AB  - INTRODUCTION: Improved understanding of risk factors for developing active
      tuberculosis (TB) will better inform decisions about diagnostic testing and
      treatment for latent TB infection (LTBI) in migrant populations in low-incidence
      regions. We aim to examine TB risk factors among the foreign-born population in
      British Columbia (BC), Canada, and to create and validate a clinically relevant
      multivariate risk score to predict active TB. METHODS AND ANALYSIS: This
      retrospective population-based cohort study will include all foreign-born
      individuals who acquired permanent resident status in Canada between 1 January
      1985 and 31 December 2013 and acquired healthcare coverage in BC at any point
      during this period. Multiple administrative databases and disease registries will
      be linked, including a National Immigration Database, BC Provincial Health
      Insurance Registration, physician billings, hospitalisations, drugs dispensed
      from community pharmacies, vital statistics, HIV testing and notifications,
      cancer, chronic kidney disease and dialysis treatment, and all TB and LTBI
      testing and treatment data in BC. Extended proportional hazards regression will
      be used to estimate risk factors for TB and to create a prognostic TB risk score.
      ETHICS AND DISSEMINATION: Ethical approval for this study has been obtained from
      the University of British Columbia Clinical Ethics Review Board. Once completed,
      study findings will be presented at conferences and published in peer-reviewed
      journals. An online TB risk score calculator will also be created.

PMID- 27888182
TI  - Feasibility of using text message reminders to increase fulfilment of emergency
      contraception prescriptions by adolescents.

PMID- 27888181
TI  - Postponing menstruation: choices and concerns.

PMID- 27888180
TI  - Northern Manhattan Hispanic Caregiver Intervention Effectiveness Study: protocol
      of a pragmatic randomised trial comparing the effectiveness of two established
      interventions for informal caregivers of persons with dementia.
AB  - INTRODUCTION: The prevalence of dementia is increasing without a known cure,
      resulting in an increasing number of informal caregivers. Caring for a person
      with dementia results in increased stress and depressive symptoms. There are
      several behavioural interventions designed to alleviate stress and depressive
      symptoms in caregivers of persons with dementia with evidence of efficacy. Two of
      the best-known interventions are the New York University Caregiver Intervention
      (NYUCI) and the Resources for Enhancing Alzheimer's Caregivers Health (REACH).
      The effectiveness of the NYUCI and REACH has never been compared. There is also a
      paucity of data on which interventions are more effective in Hispanics in New
      York City. Thus, we proposed the Northern Manhattan Hispanic Caregiver
      intervention Effectiveness Study (NHiCE), a pragmatic clinical trial designed to
      compare the effectiveness of adaptations of the NYUCI and the REACH in informal
      Hispanic caregivers of persons with dementia in New York City. METHODS AND
      ANALYSIS: NHiCE is a 6-month randomised controlled trial comparing the
      effectiveness of adaptations of the NYUCI and REACH among 200 Hispanic informal
      adult caregivers of persons with dementia. The planned number of sessions of the
      NYUCI and REACH are similar. The primary outcome measures are changes from
      baseline to 6 months in the Zarit Caregiver Burden Scale and Geriatric Depression
      Scale. Our primary approach to analyses will be intent-to-treat. The primary
      analyses will use mixed random effects models, and a full information maximum
      likelihood approach, with sensitivity analyses using generalised estimating
      equation. ETHICS AND DISSEMINATION: NHiCE is approved by the Institutional Review
      Board of Columbia University Medical Center (protocol AAAM5150). A Data Safety
      Monitoring Board monitors the progress of the study. Dissemination will include
      reports of the characteristics of the study participants, as well as a report of
      the results of the clinical trial. TRIAL REGISTRATION NUMBER: NCT02092987, Pre
      results.

PMID- 27888183
TI  - Long-term visual and systemic prognoses of 83 cases of biopsy-proven sarcoid
      uveitis.
AB  - AIMS: To determine the long-term visual and systemic outcomes of uveitis patients
      with biopsy-proven sarcoidosis. METHODS: A retrospective study of biopsy-proven
      sarcoid uveitis, with a 3-year minimum follow-up, seen at Lyon University
      Hospital, between April 2004 and January 2016. RESULTS: A total of 83 patients
      were included, with a median age at onset of 52 (37-62) years and an unbalanced
      gender ratio (women 77.1%). Thirty-one patients had original systemic sarcoidosis
      in addition to ocular localisation, whereas 52 initially presented with isolated
      sarcoid uveitis. Among the latter, 7.7% (n=4) developed an extraocular disease
      after a median follow-up duration of 60 (44-110) months. The systemic spread in
      these patients included cutaneous sarcoids (n=2), arthritis (n=1) and multiple
      mononeuritis (n=1). Complete visual recovery was obtained for 60.2% of all
      patients and 89.2% had retrieved best-corrected visual acuity (BCVA) >20/50 in
      both eyes. A unilateral loss of BCVA of worse than 20/200 was documented in two
      patients in the isolated sarcoid uveitis group. No patient suffered from
      bilateral severe visual impairment or blindness. Factors linked to a poor visual
      prognosis, defined by BCVA <=20/50 in at least one eye, were chronic macular
      oedema (p=0.009) and persistent ocular inflammation (p=0.0005). CONCLUSIONS: In
      this large European series of biopsy-proven sarcoidosis to date, with a prolonged
      follow-up, sarcoid uveitis was suggestive of a favourable systemic and visual
      outcome. Clinically isolated uveitis that revealed sarcoidosis remained a
      strictly ocular condition in most cases.

PMID- 27888185
TI  - Registries, codifications and cardiovascular outcomes in familial
      hypercholesterolaemia.

PMID- 27888184
TI  - Amnion-assisted conjunctival epithelial redirection in limbal stem cell grafting.
AB  - AIMS: To develop a technique using amniotic membrane (AM) to prevent admixture of
      conjunctival epithelial cells and limbal explant-derived corneal epithelial cells
      in patients undergoing limbal stem cell transplantation. To compare this
      technique with the current method of 'sequential sector conjunctival
      epitheliectomy' (SSCE). METHODS: 26 patients with total limbal stem cell
      deficiency who underwent ocular surface reconstruction with limbal stem cells
      transplantation were retrospectively studied. Patients were categorised into
      group A (11) in which AM was used to direct the conjunctival epithelial cells
      away from the corneal surface so that the latter could be covered by the limbal
      explant-derived epithelial cells-the procedure was termed 'amnion-assisted
      conjunctival epithelial redirection' (ACER)-and group B (15) in which the
      conjunctival epithelium was prevented from migrating on to the corneal surface by
      SSCE. RESULTS: In nine eyes of group A, the conjunctival epithelium was
      successfully directed on to the AM, preventing admixture with limbal explant
      derived corneal epithelial cells. The AM was removed or it came off spontaneously
      within 1-4 weeks. Patients treated with SSCE (group B) underwent two to four
      interventions until complete re-epithelialisation. 12 patients had pain or
      discomfort. 11 patients had conjunctival haemorrhage during SSCE. The cornea was
      epithelised from the limbal explant-derived epithelium in all patients.
      CONCLUSIONS: ACER is a viable option in limbal transplantation that reduces
      multiple patient visits, bleeding and pain that can be associated with SSCE.

PMID- 27888187
TI  - What does the ALSFRS-R really measure? A longitudinal and survival analysis of
      functional dimension subscores in amyotrophic lateral sclerosis.
AB  - INTRODUCTION: ALS functional rating scale (revised) (ALSFRS-R) is the most widely
      used functional rating system in patients with amyotrophic lateral sclerosis
      (ALS). However, heterogeneity in ALSFRS-R progression renders analysis
      challenging. We have explored the characteristics of total ALSFRS-R, and ALSFRS-R
      subscores in longitudinal and survival models, to determine whether subscore
      analysis enhances the precision of the instrument. METHODS: All cases with ALSFRS
      R scores on the Irish ALS register were included. ALSFRS-R subscores were defined
      for bulbar, motor and respiratory domains. Longitudinal models were used to
      visualise fitted total ALSFRS-R and ALSFRS-R subscore progression. In addition,
      the prognostic value of convenience and computed ALSFRS-R slope and subscore
      slopes were compared. RESULTS: 407 incident cases were identified with a complete
      ALSFRS-R measure. 233 (57%) patients were male, and 125 (31%) had bulbar-onset
      disease. ALSFRS-R bulbar and motor subscore slopes provided a better fit in
      prognostic models when combined over the total ALSFRS-R slope. Longitudinal
      analysis revealed that the ALSFRS-R motor subscore deteriorated earlier in spinal
      onset disease over bulbar-onset disease, while in bulbar-onset disease the ALSFRS
      R bulbar subscore deteriorated earlier and faster than in spinal-onset disease.
      DISCUSSION: Our analysis builds on previous knowledge of ALSFRS-R subscores.
      Decline in ALSFRS-R motor subscores in patients with spinal-onset disease, and
      decline in ALSFRS-R bulbar subscores in patients with bulbar-onset disease, may
      predate reported disease onset dates. Respiratory subscores were not
      prognostically informative after adjustment for bulbar and motor subscores. These
      results provide robust evidence that the ALSFRS-R should not be reported as a
      single combined score, but rather as domain specific subscores.

PMID- 27888186
TI  - Velocity of intraneural blood flow is increased in inflammatory neuropathies:
      sonographic observation.

PMID- 27888188
TI  - Corrigendum.

PMID- 27888189
TI  - Patients who self-monitor or self-manage can improve the quality of their oral
      anticoagulation therapy.

PMID- 27888190
TI  - Tfap2 and Sox1/2/3 cooperatively specify ectodermal fates in ascidian embryos.
AB  - Epidermis and neural tissues differentiate from the ectoderm in animal embryos.
      Although epidermal fate is thought to be induced in vertebrate embryos,
      embryological evidence has indicated that no intercellular interactions during
      early stages are required for epidermal fate in ascidian embryos. To test this
      hypothesis, we determined the gene regulatory circuits for epidermal and neural
      specification in the ascidian embryo. These circuits started with Tfap2-r.b and
      Sox1/2/3, which are expressed in the ectodermal lineage immediately after zygotic
      genome activation. Tfap2-r.b expression was diminished in the neural lineages
      upon activation of fibroblast growth factor signaling, which is known to induce
      neural fate, and sustained only in the epidermal lineage. Tfap2-r.b specified the
      epidermal fate cooperatively with Dlx.b, which was activated by Sox1/2/3 This
      Sox1/2/3-Dlx.b circuit was also required for specification of the anterior neural
      fate. In the posterior neural lineage, Sox1/2/3 activated Nodal, which is
      required for specification of the posterior neural fate. Our findings support the
      hypothesis that the epidermal fate is specified autonomously in ascidian embryos.

PMID- 27888192
TI  - Atypical chemokine receptor ACKR2 controls branching morphogenesis in the
      developing mammary gland.
AB  - Macrophages are important regulators of branching morphogenesis during
      development and postnatally in the mammary gland. Regulation of macrophage
      dynamics during these processes can therefore have a profound impact on
      development. We demonstrate here that the developing mammary gland expresses high
      levels of inflammatory CC-chemokines, which are essential in vivo regulators of
      macrophage migration. We further demonstrate that the atypical chemokine receptor
      ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed
      during mammary gland development. We have previously shown that ACKR2 regulates
      macrophage dynamics during lymphatic vessel development. Here, we extend these
      observations to reveal a novel role for ACKR2 in regulating the postnatal
      development of the mammary gland. Specifically, we show that Ackr2-/- mice
      display precocious mammary gland development. This is associated with increased
      macrophage recruitment to the developing gland and increased density of the
      ductal epithelial network. These data demonstrate that ACKR2 is an important
      regulator of branching morphogenesis in diverse biological contexts and provide
      the first evidence of a role for chemokines and their receptors in postnatal
      development processes.

PMID- 27888191
TI  - Wt1 directs the lineage specification of sertoli and granulosa cells by
      repressing Sf1 expression.
AB  - Supporting cells (Sertoli and granulosa) and steroidogenic cells (Leydig and
      theca-interstitium) are two major somatic cell types in mammalian gonads, but the
      mechanisms that control their differentiation during gonad development remain
      elusive. In this study, we found that deletion of Wt1 in the ovary after sex
      determination caused ectopic development of steroidogenic cells at the embryonic
      stage. Furthermore, differentiation of both Sertoli and granulosa cells was
      blocked when Wt1 was deleted before sex determination and most genital ridge
      somatic cells differentiated into steroidogenic cells in both male and female
      gonads. Further studies revealed that WT1 repressed Sf1 expression by directly
      binding to the Sf1 promoter region, and the repressive function was completely
      abolished when WT1 binding sites were mutated. This study demonstrates that Wt1
      is required for the lineage specification of both Sertoli and granulosa cells by
      repressing Sf1 expression. Without Wt1, the expression of Sf1 was upregulated and
      the somatic cells differentiated into steroidogenic cells instead of supporting
      cells. Our study uncovers a novel mechanism of somatic cell differentiation
      during gonad development.

PMID- 27888193
TI  - Conserved and novel functions of programmed cellular senescence during vertebrate
      development.
AB  - Cellular senescence, a form of stable cell cycle arrest that is traditionally
      associated with tumour suppression, has been recently found to occur during
      mammalian development. Here, we show that cell senescence is an intrinsic part of
      the developmental programme in amphibians. Programmed senescence occurs in
      specific structures during defined time windows during amphibian development. It
      contributes to the physiological degeneration of the amphibian pronephros and to
      the development of the cement gland and oral cavity. In both contexts, senescence
      depends on TGFbeta but is independent of ERK/MAPK activation. Furthermore,
      elimination of senescent cells through temporary TGFbeta inhibition leads to
      developmental defects. Our findings uncover conserved and new roles of senescence
      in vertebrate organogenesis and support the view that cellular senescence may
      have arisen in evolution as a developmental mechanism.

PMID- 27888194
TI  - A set of simple cell processes is sufficient to model spiral cleavage.
AB  - During cleavage, different cellular processes cause the zygote to become
      partitioned into a set of cells with a specific spatial arrangement. These
      processes include the orientation of cell division according to: an animal
      vegetal gradient; the main axis (Hertwig's rule) of the cell; and the contact
      areas between cells or the perpendicularity between consecutive cell divisions
      (Sachs' rule). Cell adhesion and cortical rotation have also been proposed to be
      involved in spiral cleavage. We use a computational model of cell and tissue
      biomechanics to account for the different existing hypotheses about how the
      specific spatial arrangement of cells in spiral cleavage arises during
      development. Cell polarization by an animal-vegetal gradient, a bias to
      perpendicularity between consecutive cell divisions (Sachs' rule), cortical
      rotation and cell adhesion, when combined, reproduce the spiral cleavage, whereas
      other combinations of processes cannot. Specifically, cortical rotation is
      necessary at the 8-cell stage to direct all micromeres in the same direction. By
      varying the relative strength of these processes, we reproduce the spatial
      arrangement of cells in the blastulae of seven different invertebrate species.

PMID- 27888195
TI  - Remodeling of adhesion and modulation of mechanical tensile forces during
      apoptosis in Drosophila epithelium.
AB  - Apoptosis is a mechanism of eliminating damaged or unnecessary cells during
      development and tissue homeostasis. During apoptosis within a tissue, the
      adhesions between dying and neighboring non-dying cells need to be remodeled so
      that the apoptotic cell is expelled. In parallel, contraction of actomyosin
      cables formed in apoptotic and neighboring cells drives cell extrusion. To date,
      the coordination between the dynamics of cell adhesion and the progressive
      changes in tissue tension around an apoptotic cell is not fully understood. Live
      imaging of histoblast expansion, which is a coordinated tissue replacement
      process during Drosophila metamorphosis, shows remodeling of adherens junctions
      (AJs) between apoptotic and non-dying cells, with a reduction in the levels of AJ
      components, including E-cadherin. Concurrently, surrounding tissue tension is
      transiently released. Contraction of a supra-cellular actomyosin cable, which
      forms in neighboring cells, brings neighboring cells together and further
      reshapes tissue tension toward the completion of extrusion. We propose a model in
      which modulation of tissue tension represents a mechanism of apoptotic cell
      extrusion.

PMID- 27888196
TI  - Differential temporal control of Foxa.a and Zic-r.b specifies brain versus
      notochord fate in the ascidian embryo.
AB  - In embryos of an invertebrate chordate, Ciona intestinalis, two transcription
      factors, Foxa.a and Zic-r.b, are required for specification of the brain and the
      notochord, which are derived from distinct cell lineages. In the brain lineage,
      Foxa.a and Zic-r.b are expressed with no temporal overlap. In the notochord
      lineage, Foxa.a and Zic-r.b are expressed simultaneously. In the present study,
      we found that the temporally non-overlapping expression of Foxa.a and Zic-r.b in
      the brain lineage was regulated by three repressors: Prdm1-r.a (formerly called
      BZ1), Prdm1-r.b (BZ2) and Hes.a. In morphant embryos of these three repressor
      genes, Foxa.a expression was not terminated at the normal time, and Zic-r.b was
      precociously expressed. Consequently, Foxa.a and Zic-r.b were expressed
      simultaneously, which led to ectopic activation of Brachyury and its downstream
      pathways for notochord differentiation. Thus, temporal controls by
      transcriptional repressors are essential for specification of the two distinct
      fates of brain and notochord by Foxa.a and Zic-r.b Such a mechanism might enable
      the repeated use of a limited repertoire of transcription factors in
      developmental gene regulatory networks.

PMID- 27888199
TI  - Risk factors for decreased cardiac output after coronary artery bypass grafting:
      a prospective cohort study.
AB  - BACKGROUND: No previous study has investigated the predictive risk factors of the
      nursing diagnosis of risk for decreased cardiac output after coronary artery
      bypass grafting (CABG). AIMS: This study aimed to identify the predictive risk
      factors of the nursing diagnosis of risk for decreased cardiac output after CABG.
      METHODS: This was a prospective cohort study performed at a cardiac university
      hospital in Sao Paulo, Brazil and 257 adult patients undergoing CABG were
      included. Potential risk factors for low cardiac output in the immediate post
      operative period were investigated using the patients' medical records.
      Univariate analysis and logistic regression were used to identify the predictive
      risk factors of decreased cardiac output. The area under the receiver operating
      characteristic curve was calculated as a measure of accuracy. The variables that
      could not be analysed through logistic regression were analysed through Fisher's
      exact test. RESULTS: One hundred and ninety-five patients had low cardiac output
      in the immediate post-operative period. The predictive risk factors included age
      ?60 years, decreased left ventricle ejection fraction, not using the radial
      artery graft, positive fluid balance and post-operative arrhythmia that differed
      from the pre-operative arrhythmia. This model predicted the outcome with a
      sensitivity of 62.9%, a specificity of 87.2% and an accuracy of 81.5%. The
      variables analysed through Fisher's exact test included heart failure, re
      exploration and bleeding-related re-exploration. CONCLUSIONS: The predictive risk
      factors for the nursing diagnosis of risk for decreased cardiac output after CABG
      were found. These results can be used to direct nurses in patient monitoring,
      staff training and nursing team staffing.

PMID- 27888197
TI  - Islet adaptations in fetal sheep persist following chronic exposure to high
      norepinephrine.
AB  - Complications in pregnancy elevate fetal norepinephrine (NE) concentrations.
      Previous studies in NE-infused sheep fetuses revealed that sustained exposure to
      high NE resulted in lower expression of alpha2-adrenergic receptors in islets and
      increased insulin secretion responsiveness after acutely terminating the NE
      infusion. In this study, we determined if the compensatory increase in insulin
      secretion after chronic elevation of NE is independent of hyperglycemia in sheep
      fetuses and whether it is persistent in conjunction with islet desensitization to
      NE. After an initial assessment of glucose-stimulated insulin secretion (GSIS) at
      129 +/- 1 days of gestation, fetuses were continuously infused for seven days
      with NE and maintained at euglycemia with a maternal insulin infusion. Fetal GSIS
      studies were performed again on days 8 and 12. Adrenergic sensitivity was
      determined in pancreatic islets collected at day 12. NE infusion increased (P <
      0.01) fetal plasma NE concentrations and lowered (P < 0.01) basal insulin
      concentrations compared to vehicle-infused controls. GSIS was 1.8-fold greater (P
      < 0.05) in NE-infused fetuses compared to controls at both one and five days
      after discontinuing the infusion. Glucose-potentiated arginine-induced insulin
      secretion was also enhanced (P < 0.01) in NE-infused fetuses. Maximum GSIS in
      islets isolated from NE-infused fetuses was 1.6-fold greater (P < 0.05) than
      controls, but islet insulin content and intracellular calcium signaling were not
      different between treatments. The half-maximal inhibitory concentration for NE
      was 2.6-fold greater (P < 0.05) in NE-infused islets compared to controls. These
      findings show that chronic NE exposure and not hyperglycemia produce persistent
      adaptations in pancreatic islets that augment beta-cell responsiveness in part
      through decreased adrenergic sensitivity.

PMID- 27888200
TI  - Effect of Principal Component Analysis Centering and Scaling on Classification of
      Mycobacteria from Raman Spectra.
AB  - Raman spectroscopy has been used for decades to detect and identify biological
      substances as it provides specific molecular information. Spectra collected from
      biological samples are often complex, requiring the aid of data truncation
      techniques such as principal component analysis (PCA) and multivariate
      classification methods. Classification results depend on the proper selection of
      principal components (PCs) and how PCA is performed (scaling and/or centering).
      There are also guidelines for choosing the optimal number of PCs such as a scree
      plot, Kaiser criterion, or cumulative percent variance. The goal of this research
      is to evaluate these methods for best implementation of PCA and PC selection to
      classify Raman spectra of bacteria. Raman spectra of three different isolates of
      mycobacteria ( Mycobacterium sp. JLS, Mycobacterium sp. KMS, Mycobacterium sp.
      MCS) were collected and then passed through PCA and linear discriminant analysis
      for classification. Principal component analysis implementation as well as PC
      selection was evaluated by comparing the highest possible classification
      accuracies against accuracies determined by PC selection methods for each
      centering and scaling option. Centered and unscaled data provided the best
      results when selecting PCs based on cumulative percent variance.

PMID- 27888198
TI  - Ovarian characteristics in sheep with multiple fecundity genes.
AB  - Ewes heterozygous for combinations of the Inverdale (FecXI; I+), Booroola (FecB;
      B+) and Woodlands (FecX2W; W+) mutations have ovulation rates higher than each
      mutation separately. The aims of the experiments described herein were to examine
      the ovarian phenotypes in I+B+ and I+B+W+ ewes and to compare these with the
      appropriate ++ (controls), I+ and BB animals available for this study. The mean
      +/- s.e.m. ovulation rates in the ++ (n = 23), I+ (10), I+B+ (7), I+B+W+ (10) and
      BB (3) animals were 1.8 +/- 0.1, 2.5 +/- 0.2, 6.6 +/- 1.0, 9.6 +/- 0.9 and 9.7 +/
      0.9 respectively. The maximum number of granulosa cells per follicle in the ++
      and I+ genotypes was accumulated after exceeding 5 mm diameter, whereas in I+B+,
      I+B+W+ and BB animals, this was achieved when follicles reached >2-3 mm. The
      number of putative preovulatory follicles, as assessed from those with LH
      responsive granulosa cells, 24 h after the induction of luteolysis, was higher (P
      < 0.01) in the I+B+ and I+B+W+ compared to the ++ and I+ genotypes. The median
      follicular diameters of these follicles in the ++, I+, I+B+, I+B+W+ and BB
      genotypes were 6, 5, 3, 3 and 3 mm respectively. The total number of granulosa
      cells in the putative preovulatory follicles when added together, and total mass
      of luteal tissue, did not differ between the genotypes. Thus, despite large
      ovulation rate differences between animals with one or more fecundity genes, the
      total cell compositions over all preovulatory follicles and corpora lutea, when
      added together, are similar to that from the one or two such follicles in the
      wild types.

PMID- 27888201
TI  - Increasing trunk flexion transforms human leg function into that of birds despite
      different leg morphology.
AB  - Pronograde trunk orientation in small birds causes prominent intra-limb
      asymmetries in the leg function. As yet, it is not clear whether these
      asymmetries induced by the trunk reflect general constraints on the leg function
      regardless of the specific leg architecture or size of the species. To address
      this, we instructed 12 human volunteers to walk at a self-selected velocity with
      four postures: regular erect, or with 30 deg, 50 deg and maximal trunk flexion.
      In addition, we simulated the axial leg force (along the line connecting hip and
      centre of pressure) using two simple models: spring and damper in series, and
      parallel spring and damper. As trunk flexion increases, lower limb joints become
      more flexed during stance. Similar to birds, the associated posterior shift of
      the hip relative to the centre of mass leads to a shorter leg at toe-off than at
      touchdown, and to a flatter angle of attack and a steeper leg angle at toe-off.
      Furthermore, walking with maximal trunk flexion induces right-skewed vertical and
      horizontal ground reaction force profiles comparable to those in birds.
      Interestingly, the spring and damper in series model provides a superior
      prediction of the axial leg force across trunk-flexed gaits compared with the
      parallel spring and damper model; in regular erect gait, the damper does not
      substantially improve the reproduction of the human axial leg force. In
      conclusion, mimicking the pronograde locomotion of birds by bending the trunk
      forward in humans causes a leg function similar to that of birds despite the
      different morphology of the segmented legs.

PMID- 27888202
TI  - Jim Bear: Delineating the mechanics of cell migration.

PMID- 27888203
TI  - GTSE1 leads cancer cells into CIN.

PMID- 27888204
TI  - No ATG8s, no problem? How LC3/GABARAP proteins contribute to autophagy.
AB  - The ATG8 family LC3/GABARAP proteins are attached to the membrane of nascent
      autophagosomes, but their functions during autophagy are unclear. In this issue,
      Nguyen et al. (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201607039) show
      that LC3/GABARAP proteins are not essential for autophagosome formation but are
      critical for autophagosome-lysosome fusion.

PMID- 27888205
TI  - Engagement in the HIV care cascade and barriers to antiretroviral therapy uptake
      among female sex workers in Port Elizabeth, South Africa: findings from a
      respondent-driven sampling study.
AB  - BACKGROUND: Female sex workers (FSWs) are disproportionately affected by HIV,
      even in the context of broadly generalised HIV epidemics such as South Africa.
      This has been observed in spite of the individual and population-level benefits
      of HIV treatment. We characterise the HIV care cascade among FSWs and
      relationships with antiretroviral therapy (ART) use. METHODS: FSWs >=18 years
      were recruited through respondent-driven sampling into a cross-sectional study in
      Port Elizabeth, South Africa. Participants completed questionnaires and received
      HIV and syphilis testing; CD4 counts were assessed among women living with HIV.
      Engagement in the HIV care cascade is described, and correlates of self-reported
      ART use among treatment-eligible previously diagnosed FSWs were estimated using
      robust Poisson regression. RESULTS: Between October 2014 and April 2015, 410 FSWs
      participated in study activities. Overall, 261/410 were living with HIV
      (respondent-driven sampling-weighted prevalence 61.5% (95% bootstrapped CI 54.1%
      to 68.0%)). Prior diagnosis of HIV was relatively high (214/261, 82%); however,
      ART coverage among FSWs living with HIV was 39% (102/261). In multivariate
      analyses, FSWs were less likely to be on ART if they had not disclosed their HIV
      status to non-paying partners (adjusted prevalence ratio (aPR) 0.43, 95% CI 0.22
      to 0.86, where the reference is FSWs without non-paying partners), and also if
      they engaged in mobile healthcare services (aPR 0.71, 95% CI 0.57 to 0.89).
      CONCLUSIONS: HIV testing and awareness of HIV status were high, but substantial
      losses in the cascade occur at treatment initiation. Given that FSWs engaged in
      mobile HIV testing and peer education programmes have unmet HIV treatment needs,
      models of decentralised treatment provision such as mobile-based ART care should
      be evaluated.

PMID- 27888206
TI  - Access of non-specialist sexual health services by men who have sex with men: do
      they differ from those attending specialist services?
AB  - OBJECTIVES: Men who have sex with men (MSM) bear a disproportionate burden of
      STIs. While routine STI surveillance data suggest MSM regularly access specialist
      genitourinary medicine (GUM) clinics for their sexual healthcare, the extent to
      which MSM attend non-specialist sexual health services (SHSs) is unclear.
      METHODS: We used data from the GUM Clinic Activity Data Set (GUMCADv2), the
      national STI surveillance system, to compare the characteristics, service usage
      and STI outcomes of MSM accessing specialist and non-specialist (non-GUM) SHSs in
      England in 2014. Pearson's chi2, Student's t-test and logistic regression
      analysis were used. RESULTS: Where sexual orientation was recorded (92%), 11%
      (4552/41 597) of non-GUM attendances were among MSM compared with 28% (280
      466/999 331) of GUM attendances (p<0.001). Compared with those attending GUM
      services, MSM attending non-GUM services were younger (mean age: 30.2 years vs
      37.7 years; p<0.001) and were more likely to be of mixed ethnicity (4.9% vs 3.5%;
      p<0.001), to have had a full sexual health screen (chlamydia, gonorrhoea,
      syphilis and HIV tests) (48.0% vs 37.0%; p<0.001) and to be diagnosed with
      chlamydia (7.4% vs 4.1%; p<0.001) and gonorrhoea (8.5% vs 6.5%: p<0.001). MSM
      attending non-GUM services had slightly lower HIV test uptake (87.0% vs 95.0%;
      p=0.157) and were less likely to be diagnosed with HIV (0.5% vs 0.8%; p=0.019),
      compared with those attending GUM clinics. CONCLUSIONS: Non-specialist SHSs play
      an important role in the care of MSM and should ensure services meet their needs.

PMID- 27888207
TI  - New media challenges and opportunities.

PMID- 27888208
TI  - Double trouble: tPA-induced angioedema.

PMID- 27888210
TI  - Management of young competitive athletes with cardiovascular conditions.

PMID- 27888209
TI  - Optimal duration of dual antiplatelet therapy after acute coronary syndromes and
      coronary stenting.

PMID- 27888211
TI  - Biceps femoris architecture: the association with injury and response to
      training.

PMID- 27888212
TI  - Back to basics with some new tools: first ensure the safety of sporting
      environments.

PMID- 27888213
TI  - Coach-directed education is associated with injury-prevention behaviour in
      players: an ecological cross-sectional study.
AB  - BACKGROUND/AIM: Rugby union ('rugby') presents an above-average risk of injury to
      participants. BokSmart is a South African nationwide intervention that aims to
      reduce rugby-related injuries in players. This is achieved by educating coaches
      and referees to improve injury behaviour of players. Thus, the aim of this study
      was to assess if the receipt of injury-prevention education was associated with
      player behaviour. METHODS: Junior (n=2279) and senior (n=1642) players, who
      attended merit-based South African Rugby tournaments (2008-2012), completed an
      anonymous questionnaire. Logistic regressions investigated if player injury
      prevention behaviours were associated with the receipt of education on the same
      topic. Additionally, players' preferred sources of education were explored
      through frequency and chi2 analyses. RESULTS: Of the 16 injury-prevention
      behaviours, 12 (75%) were associated with receiving education on that topic. The
      four behaviours not associated with education were: warming-up (before training
      and matches), and avoiding heat and massage post injury. Of the seven possible
      sources of this education, the majority of players chose either coaches or
      physiotherapists as their preferred media. In comparison with junior players,
      more senior players chose physiotherapists instead of coaches for warming-up and
      cooling-down education. CONCLUSIONS: The results of this study support, to a
      large degree, the strategy of BokSmart-influence of player behaviour through
      coach education. However, these findings also suggest that BokSmart could target
      team physiotherapists in addition to coaches and referees with their safety
      education. Also, players might have different preferences for this education
      depending on their age.

PMID- 27888214
TI  - Cardiorespiratory fitness and death from cancer: a 42-year follow-up from the
      Copenhagen Male Study.
AB  - OBJECTIVES: Poor cardiorespiratory fitness (CRF) is associated with death from
      cancer. If follow-up time is short, this association may be confounded by
      subclinical disease already present at the time of CRF assessment. This study
      investigates the association between CRF and death from cancer and any cause with
      42 years and 44 years of follow-up, respectively. SETTING, PARTICIPANTS AND MAIN
      OUTCOME MEASURES: Middle-aged, employed and cancer-free Danish men from the
      prospective Copenhagen Male Study, enrolled in 1970-1971, were included. CRF
      (maximal oxygen consumption (VO2max)) was estimated using a bicycle ergometer
      test and analysed in multivariable Cox models including conventional risk
      factors, social class and self-reported physical activity. Death from cancer and
      all-cause mortality was assessed using Danish national registers. Follow-up was
      100% complete. RESULTS: In total, 5131 men were included, mean (SD) age 48.8
      (5.4) years. During 44 years of follow-up, 4486 subjects died (87.4%), 1527
      (29.8%) from cancer. In multivariable models, CRF was highly significantly
      inversely associated with death from cancer and all-cause mortality ((HR (95%
      CI)) 0.83 (0.77 to 0.90) and 0.89 (0.85 to 0.93) per 10 mL/kg/min increase in
      estimated VO2max, respectively). A similar association was seen across specific
      cancer groups, except death from prostate cancer (1.00 (0.82 to 1.2); p=0.97;
      n=231). The associations between CRF and outcomes remained essentially unchanged
      after excluding subjects dying within 10 years (n=377) and 20 years (n=1276) of
      inclusion. CONCLUSIONS: CRF is highly significantly inversely associated with
      death from cancer and all-cause mortality. The associations are robust for
      exclusion of subjects dying within 20 years of study inclusion, thereby
      suggesting a minimal influence of reverse causation.

PMID- 27888215
TI  - Super-resolution microscopy reveals the insulin-resistance-regulated
      reorganization of GLUT4 on plasma membranes.
AB  - GLUT4 (also known as SLC2A4) is essential for glucose uptake in skeletal muscles
      and adipocytes, which play central roles in whole-body glucose metabolism. Here,
      using direct stochastic optical reconstruction microscopy (dSTORM) to investigate
      the characteristics of plasma-membrane-fused GLUT4 at the single-molecule level,
      we have demonstrated that insulin and insulin resistance regulate the spatial
      organization of GLUT4 in adipocytes. Stimulation with insulin shifted the balance
      of GLUT4 on the plasma membrane toward a more dispersed configuration. In
      contrast, insulin resistance induced a more clustered distribution of GLUT4 and
      increased the mean number of molecules per cluster. Furthermore, our data
      demonstrate that the F5QQI motif and lipid rafts mediate the maintenance of GLUT4
      clusters on the plasma membrane. Mutation of F5QQI (F5QQA-GLUT4) induced a more
      clustered distribution of GLUT4; moreover, destruction of lipid rafts in
      adipocytes expressing F5QQA-GLUT4 dramatically decreased the percentage of large
      clusters and the mean number of molecules per cluster. In conclusion, our data
      clarify the effects of insulin stimulation or insulin resistance on GLUT4
      reorganization on the plasma membrane and reveal new pathogenic mechanisms of
      insulin resistance.

PMID- 27888216
TI  - Drosophila Sulf1 is required for the termination of intestinal stem cell division
      during regeneration.
AB  - Stem cell division is activated to trigger regeneration in response to tissue
      damage. The molecular mechanisms by which this stem cell mitotic activity is
      properly repressed at the end of regeneration are poorly understood. Here, we
      show that a specific modification of heparan sulfate is crucial for regulating
      Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis
      and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1
      resulted in increased ISC division during normal homeostasis, which was caused by
      upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog
      pathways. Using a regeneration model, we found that ISCs failed to properly halt
      division at the termination stage in Sulf1 mutants, showing that Sulf1 is
      required for terminating ISC division at the end of regeneration. We propose that
      post-transcriptional regulation of mitogen signaling by heparan sulfate
      structural modifications provides a new regulatory step for precise temporal
      control of stem cell activity during regeneration.

PMID- 27888217
TI  - A quantitative FastFUCCI assay defines cell cycle dynamics at a single-cell
      level.
AB  - The fluorescence ubiquitination-based cell cycle indicator (FUCCI) is a powerful
      tool for use in live cells but current FUCCI-based assays have limited throughput
      in terms of image processing and quantification. Here, we developed a lentiviral
      system that rapidly introduced FUCCI transgenes into cells by using an all-in-one
      expression cassette, FastFUCCI. The approach alleviated the need for sequential
      transduction and characterisation, improving labelling efficiency. We coupled the
      system to an automated imaging workflow capable of handling large datasets. The
      integrated assay enabled analyses of single-cell readouts at high spatiotemporal
      resolution. With the assay, we captured in detail the cell cycle alterations
      induced by antimitotic agents. We found that treated cells accumulated at G2 or M
      phase but eventually advanced through mitosis into the next interphase, where the
      majority of cell death occurred, irrespective of the preceding mitotic phenotype.
      Some cells appeared viable after mitotic slippage, and a fraction of them
      subsequently re-entered S phase. Accordingly, we found evidence that targeting
      the DNA replication origin activity sensitised cells to paclitaxel. In summary,
      we demonstrate the utility of the FastFUCCI assay for quantifying spatiotemporal
      dynamics and identify its potential in preclinical drug development.

PMID- 27888218
TI  - Diverting CERT-mediated ceramide transport to mitochondria triggers Bax-dependent
      apoptosis.
AB  - A deregulation of ceramide biosynthesis in the endoplasmic reticulum (ER) is
      frequently linked to induction of mitochondrial apoptosis. Although in vitro
      studies suggest that ceramides might initiate cell death by acting directly on
      mitochondria, their actual contribution to the apoptotic response in living cells
      is unclear. Here, we have analyzed the consequences of targeting the biosynthetic
      flow of ceramides to mitochondria using a ceramide transfer protein (encoded by
      COL4A3BP) equipped with an OMM anchor, mitoCERT. Cells expressing mitoCERT import
      ceramides into mitochondria and undergo Bax-dependent apoptosis. Apoptosis
      induction by mitoCERT was abolished through (i) removal of its ceramide transfer
      domain, (ii) disruption of its interaction with VAMP-associated proteins (VAPs)
      in the ER, (iii) addition of antagonistic CERT inhibitor HPA12, (iv) blocking de
      novo ceramide synthesis and (v) targeting of a bacterial ceramidase to
      mitochondria. Our data provide the first demonstration that translocation of ER
      ceramides to mitochondria specifically commits cells to death and establish
      mitoCERT as a valuable new tool to unravel the molecular principles underlying
      ceramide-mediated apoptosis.

PMID- 27888219
TI  - Long-term intestinal bleeding in a child: a rare case of heterotopic gastric
      mucosa in the jejunum.
AB  - We report a rare case of heterotopic gastric mucosa presenting in a jejunal polyp
      of a 9-year-old girl, diagnosed with capsule endoscopy and laparoscopic
      exploration, after a 15-month history of lower gastrointestinal bleeding and
      anaemia. During surgery, the jejunal segment containing the polyp was resected
      and pathological examination revealed a polyp with gastric heterotopia.
      Heterotopic gastric mucosa is a rare pathology characterised by the presence of
      gastric mucosa outside of the stomach. Heterotopic gastric mucosa usually occurs
      in the oesophagus, duodenum, Meckel's diverticulum and enteric duplication cysts.
      It can be either congenital (heterotopic) or acquired (metaplastic). Symptoms
      vary from mild dyspepsia to massive gastrointestinal bleeding.

PMID- 27888220
TI  - Castleman's disease in carcinoma gall bladder.
AB  - Castleman's disease (CD) also known as angiofollicular lymph node hyperplasia
      represents a group of uncommon non-clonal lymphoproliferation. We herein report a
      case of CD associated with carcinoma of the gall bladder. To the best of our
      knowledge, it is the first of its kind and has not been reported in the past. The
      hypothesis regarding the aetiopathogenesis of CD is that it is associated with
      interleukin-6 surges. This may be explained by the overproduction of IL-6 by
      tumour cells or IL-6 production due to a long-standing/smouldering localised
      inflammatory response. An important question raised by this observation is
      whether the finding of CD has any effect on the outcome of this patient of
      carcinoma of the gall bladder. Further research is required in this matter.

PMID- 27888221
TI  - Severe endocarditis and open-heart surgery during pregnancy.
AB  - A woman aged 36 years G2P1 presented at our outpatient clinic with symptoms of
      discomfort, dyspnoea and fever at a gestational age of 17 weeks. She was
      subsequently diagnosed with severe endocarditis with a large vegetation on the
      mitral valve. She underwent open chest mitral valve surgery while on
      cardiopulmonary bypass (CPB) within a few days. Such surgical intervention is not
      only associated with increased maternal risks, but also with severe fetal
      morbidity and mortality. In such patients, certain perioperative measures can
      diminish these risks. In this case, mitral valve plasty was successfully
      performed and no maternal complications occurred. 22 weeks later, she had an at
      term vaginal delivery of a healthy son.

PMID- 27888222
TI  - Asymptomatic colitis induced by low-dose methotrexate.
AB  - A woman aged 77 years with a history of rheumatoid arthritis (RA) presented with
      inflammatory colitis confined to her rectum, which was incidentally found by a
      screening colonoscopy. Histopathological examination of colonic biopsies showed
      non-specific inflammatory infiltrates of lymphocytes, the cause of which was
      unknown. She had been diagnosed with RA 5 years before, and she was receiving
      methotrexate 6 mg weekly, to which tocilizumab had been added 4 years earlier,
      which achieved stable control of her disease. She had no gastrointestinal
      symptoms or other health problems. Tocilizumab-induced colitis was considered
      likely, and the drug was discontinued. Metronidazole was also prescribed because
      of possible Clostridium difficile-associated colitis. 3 months later, a repeat
      colonoscopy showed no improvement of the colitis. The methotrexate was also
      discontinued, and folinic acid was prescribed daily for 2 weeks, leading to
      complete resolution of the colitis observed at repeat colonoscopy.

PMID- 27888223
TI  - Adams-Oliver syndrome associated with gastrointestinal malformations.

PMID- 27888224
TI  - Massive haemolysis, gas-forming liver abscess and sepsis due to Clostridium
      perfringens bacteraemia.
AB  - Clostridial soft tissue infections are infrequent, but can be life-threatening
      when associated with certain underlying conditions, such as immunosuppression or
      malignancy. When bacteraemia occurs, it can be accompanied by haemolysis. Only
      surgical removal of the focus of infection and early onset of antibiotic therapy
      can prevent a very poor outcome. We describe the case of a man aged 65 years who
      presented with sepsis, haemolysis and rapid worsening. The identification of a
      gas-forming liver abscess, the early percutaneous drainage and the prompt
      initiation of antibiotic treatment were the key factors in the outcome of this
      patient.

PMID- 27888225
TI  - Use of the Pipeline embolization device for recurrent and residual cerebral
      aneurysms: a safety and efficacy analysis with short-term follow-up.
AB  - OBJECTIVE: Evaluation of the safety and efficacy of the Pipeline embolization
      device (PED) when used as second-line treatment for recurrent or residual,
      pretreated ruptured and unruptured intracranial aneurysms (IAs). METHODS:
      Retrospective review of our database to include all patients who were treated
      with a PED for recurrent or residual IAs following surgical clipping or coiling.
      We evaluated neurological outcome and angiograms at discharge, 6- and 12-months'
      follow-up and assessed intimal hyperplasia at follow-up. RESULTS: Twenty-four
      patients met our inclusion criteria. Most IAs were located in the anterior
      circulation (n=21). No change of preprocedure modified Rankin Scale score was
      seen at discharge or at any scheduled follow-up. Complete or near-complete
      aneurysm occlusion on 6- and 12-month angiograms was seen in 94.4% (17/18 cases)
      and 93.3% (14/15 cases), respectively. Complete or near-complete occlusion was
      seen in 100% of previously ruptured and 85.7% (6/7 cases) and 83.3% (5/6 cases)
      of previously unruptured cases at the 6- and 12-months' follow-up, respectively.
      One case of moderate intimal hyperplasia was observed at 6 months and decreased
      to mild at the 12-months' follow-up. No difference in device performance was
      observed among pretreated unruptured or ruptured IAs. CONCLUSIONS: Treatment of
      recurrent or residual IAs with a PED after previous coiling or clipping is
      feasible and safe. There is no difference in device performance between ruptured
      or unruptured IAs.

PMID- 27888227
TI  - Heartbeat: Chronic inflammatory disorders and cardiovascular disease.

PMID- 27888228
TI  - Cardiovascular highlights from non-cardiology journals.

PMID- 27888229
TI  - Loneliness and social isolation and increased risk of coronary heart disease and
      stroke: clinical implications.

PMID- 27888226
TI  - Single-cell sequencing maps gene expression to mutational phylogenies in PDGF-
      and EGF-driven gliomas.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive type of primary
      brain tumor. Epidermal growth factor (EGF) and platelet-derived growth factor
      (PDGF) receptors are frequently amplified and/or possess gain-of-function
      mutations in GBM However, clinical trials of tyrosine-kinase inhibitors have
      shown disappointing efficacy, in part due to intra-tumor heterogeneity. To assess
      the effect of clonal heterogeneity on gene expression, we derived an approach to
      map single-cell expression profiles to sequentially acquired mutations identified
      from exome sequencing. Using 288 single cells, we constructed high-resolution
      phylogenies of EGF-driven and PDGF-driven GBMs, modeling transcriptional kinetics
      during tumor evolution. Descending the phylogenetic tree of a PDGF-driven tumor
      corresponded to a progressive induction of an oligodendrocyte progenitor-like
      cell type, expressing pro-angiogenic factors. In contrast, phylogenetic analysis
      of an EGFR-amplified tumor showed an up-regulation of pro-invasive genes. An in
      frame deletion in a specific dimerization domain of PDGF receptor correlates with
      an up-regulation of growth pathways in a proneural GBM and enhances proliferation
      when ectopically expressed in glioma cell lines. In-frame deletions in this
      domain are frequent in public GBM data.

PMID- 27888230
TI  - ToxReporter: viewing the genome through the eyes of a toxicologist.
AB  - One of the many roles of a toxicologist is to determine if an observed adverse
      event (AE) is related to a previously unrecognized function of a given
      gene/protein. Towards that end, he or she will search a variety of public and
      propriety databases for information linking that protein to the observed AE.
      However, these databases tend to present all available information about a
      protein, which can be overwhelming, limiting the ability to find information
      about the specific toxicity being investigated. ToxReporter compiles information
      from a broad selection of resources and limits display of the information to user
      selected areas of interest. ToxReporter is a PERL-based web-application which
      utilizes a MySQL database to streamline this process by categorizing public and
      proprietary domain-derived information into predefined safety categories
      according to a customizable lexicon. Users can view gene information that is 'red
      flagged' according to the safety issue under investigation. ToxReporter also uses
      a scoring system based on relative counts of the red-flags to rank all genes for
      the amount of information pertaining to each safety issue and to display their
      scored ranking as an easily interpretable 'Tox-At-A-Glance' chart. Although
      ToxReporter was originally developed to display safety information, its flexible
      design could easily be adapted to display disease information as well.Database
      URL: ToxReporter is freely available at https://github.com/mgosink/ToxReporter.

PMID- 27888233
TI  - Neurological letter from Cape Town.

PMID- 27888231
TI  - Text mining resources for the life sciences.
AB  - Text mining is a powerful technology for quickly distilling key information from
      vast quantities of biomedical literature. However, to harness this power the
      researcher must be well versed in the availability, suitability, adaptability,
      interoperability and comparative accuracy of current text mining resources. In
      this survey, we give an overview of the text mining resources that exist in the
      life sciences to help researchers, especially those employed in biocuration, to
      engage with text mining in their own work. We categorize the various resources
      under three sections: Content Discovery looks at where and how to find biomedical
      publications for text mining; Knowledge Encoding describes the formats used to
      represent the different levels of information associated with content that enable
      text mining, including those formats used to carry such information between
      processes; Tools and Services gives an overview of workflow management systems
      that can be used to rapidly configure and compare domain- and task-specific
      processes, via access to a wide range of pre-built tools. We also provide links
      to relevant repositories in each section to enable the reader to find resources
      relevant to their own area of interest. Throughout this work we give a special
      focus to resources that are interoperable-those that have the crucial ability to
      share information, enabling smooth integration and reusability.

PMID- 27888232
TI  - Parents perspectives on whole genome sequencing for their children: qualified
      enthusiasm?
AB  - OBJECTIVE: To better understand the consequences of returning whole genome
      sequencing (WGS) results in paediatrics and facilitate its evidence-based
      clinical implementation, we studied parents' experiences with WGS and their
      preferences for the return of adult-onset secondary variants (SVs)-medically
      actionable genomic variants unrelated to their child's current medical condition
      that predict adult-onset disease. METHODS: We conducted qualitative interviews
      with parents whose children were undergoing WGS as part of the SickKids Genome
      Clinic, a research project that studies the impact of clinical WGS on patients,
      families, and the healthcare system. Interviews probed parents' experience with
      and motivation for WGS as well as their preferences related to SVs. Interviews
      were analysed thematically. RESULTS: Of 83 invited, 23 parents from 18 families
      participated. These parents supported WGS as a diagnostic test, perceiving clear
      intrinsic and instrumental value. However, many parents were ambivalent about
      receiving SVs, conveying a sense of self-imposed obligation to take on the
      'weight' of knowing their child's SVs, however unpleasant. Some parents chose to
      learn about adult-onset SVs for their child but not for themselves. CONCLUSIONS:
      Despite general enthusiasm for WGS as a diagnostic test, many parents felt a duty
      to learn adult-onset SVs. Analogous to 'inflicted insight', we call this
      phenomenon 'inflicted ought'. Importantly, not all parents of children undergoing
      WGS view the best interests of their child in relational terms, thereby
      challenging an underlying justification for current ACMG guidelines for reporting
      incidental secondary findings from whole exome and WGS.

PMID- 27888234
TI  - Neuromyelitis optica presenting as acute bilateral ptosis.
AB  - Acute bilateral ptosis can be a hallmark of several serious neurological
      conditions. We present the first case of acute bilateral near-complete ptosis
      secondary to neuromyelitis optica spectrum disorder. We suggest that clinicians
      should consider this disorder among the differential diagnosis of acute bilateral
      ptosis, especially if there are other brainstem signs.

PMID- 27888235
TI  - Rare cause of abdominal pain and fever in a pregnant woman.
AB  - CLINICAL PRESENTATION: A pregnant woman (third trimester) presented with intense
      abdominal pain, nausea and myalgia. The patient was obese (body mass index 38)
      and was being treated for high blood pressure, hyperuricemia and hypothyroidism.
      She had chronic renal deficiency related to focal segmental glomerular sclerosis
      requiring dialysis. The physical examination at admission revealed a fever of 39
      degrees C and an acute abdomen with abdominal guarding in the right upper
      quadrant without hepatomegaly or splenomegaly. There were no clinical signs of
      pre-eclampsia. Fetal ultrasound and a Doppler of the umbilical vessels were
      normal. Laboratory tests showed normal liver and liver function (total protein
      95%, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin
      normal). The white cell count was 10*109/l (90% neutrophils), with a normal
      platelet count. Blood, urine and vaginal cultures were negative. Abdominal
      ultrasound revealed isolated thickening of the gallbladder wall without
      cholelithiasis. Empirical antibiotic treatment was begun with intravenous
      amoxicillin. Six days later, the patient's condition had worsened with increased
      abdominal pain, persistent fever and liver test abnormalities (AST-ALT 6N).
      However, bilirubin, hepatic synthesis tests, as well as leucocyte and platelet
      counts were still normal. A caesarean section followed by coelioscopy was
      decided. Coelioscopy revealed a liver with numerous necrotic spots (see figure
      1).gutjnl;66/11/1911/GUTJNL2016313097F1F1GUTJNL2016313097F1Figure 1Diagnostic
      laparoscopy revealed a liver surface covered with numerous white necrotic spots.
      QUESTION: What is the diagnosis?

PMID- 27888236
TI  - Schlafen-1 causes a cell cycle arrest by inhibiting induction of cyclin D1.

PMID- 27888237
TI  - Mice lacking alpha-tubulin acetyltransferase 1 are viable but display alpha
      tubulin acetylation deficiency and dentate gyrus distortion.

PMID- 27888238
TI  - Rational design of a parthenolide-based drug regimen that selectively eradicates
      acute myelogenous leukemia stem cells.

PMID- 27888239
TI  - The increasing diversity of functions attributed to the SAFB family of RNA-/DNA
      binding proteins.
AB  - RNA-binding proteins play a central role in cellular metabolism by orchestrating
      the complex interactions of coding, structural and regulatory RNA species. The
      SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like
      transcriptional modulator, SLTM), which are highly conserved evolutionarily, were
      first identified on the basis of their ability to bind scaffold attachment region
      DNA elements, but attention has subsequently shifted to their RNA-binding and
      protein-protein interactions. Initial studies identified the involvement of these
      proteins in the cellular stress response and other aspects of gene regulation.
      More recently, the multifunctional capabilities of SAFB proteins have shown that
      they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as
      well as in interaction with chromatin-modifying complexes. With the advent of new
      techniques for identifying RNA-binding sites, enumeration of individual RNA
      targets has now begun. This review aims to summarise what is currently known
      about the functions of SAFB proteins.

PMID- 27888240
TI  - Topological organisation of the phosphatidylinositol 4,5-bisphosphate
      phospholipase C resynthesis cycle: PITPs bridge the ER-PM gap.
AB  - Phospholipase C (PLC) is a receptor-regulated enzyme that hydrolyses
      phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) at the plasma membrane (PM)
      triggering three biochemical consequences, the generation of soluble inositol
      1,4,5-trisphosphate (IP3), membrane-associated diacylglycerol (DG) and the
      consumption of PM PI(4,5)P2 Each of these three signals triggers multiple
      molecular processes impacting key cellular properties. The activation of PLC also
      triggers a sequence of biochemical reactions, collectively referred to as the
      PI(4,5)P2 cycle that culminates in the resynthesis of this lipid. The biochemical
      intermediates of this cycle and the enzymes that mediate these reactions are
      topologically distributed across two membrane compartments, the PM and the
      endoplasmic reticulum (ER). At the PM, the DG formed during PLC activation is
      rapidly converted into phosphatidic acid (PA) that needs to be transported to the
      ER where the machinery for its conversion into PI is localised. Conversely, PI
      from the ER needs to be rapidly transferred to the PM where it can be
      phosphorylated by lipid kinases to regenerate PI(4,5)P2 Thus, two lipid transport
      steps between membrane compartments through the cytosol are required for the
      replenishment of PI(4,5)P2 at the PM. Here, we review the topological constraints
      in the PI(4,5)P2 cycle and current understanding how these constraints are
      overcome during PLC signalling. In particular, we discuss the role of lipid
      transfer proteins in this process. Recent findings on the biochemical properties
      of a membrane-associated lipid transfer protein of the PITP family, PITPNM
      proteins (alternative name RdgBalpha/Nir proteins) that localise to membrane
      contact sites are discussed. Studies in both Drosophila and mammalian cells
      converge to provide a resolution to the conundrum of reciprocal transfer of PA
      and PI during PLC signalling.

PMID- 27888241
TI  - Neuropsychiatry: a synthesis of clinical and scientific fields for disorders of
      mind and body.

PMID- 27888243
TI  - Critical appraisal.

PMID- 27888242
TI  - Revalidation and continuing professional development.

PMID- 27888245
TI  - Yes, marriage equality is a mental health issue.

PMID- 27888247
TI  - From the President.

PMID- 27888246
TI  - The language of psychiatry.

PMID- 27888250
TI  - Feedback on the 2012 Fellowship program.

PMID- 27888249
TI  - Talking with Emeritus Professor Sidney Bloch.

PMID- 27888253
TI  - Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for
      intramuscular immunization.
AB  - In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with
      sol-gel transition temperature around 32C as an intramuscular vaccine delivery
      system by using ovalbumin as a model antigen. First, in vitro release test showed
      that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a
      more sustainable way. From fluorescence living imaging, 50-200 mg/mL of PLGA-PEG
      PLGA formulations could release antigen in a sustainable manner in vivo,
      suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further,
      the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased
      antigen availability in the spleens of the immunized mice. The intramuscular
      immunization results showed that 50-200 mg/mL of PLGA-PEG-PLGA formulations
      promoted significantly more potent antigen-specific IgG immune response. In
      addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the
      secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation
      assay, 50-200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly
      higher splenocyte activation. These results indicate that the thermo-sensitive
      and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA
      based hydrogel) own promising potential as an intramuscular vaccine delivery
      system.

PMID- 27888254
TI  - An evaluation of the Aerie Real campaign: Potential for promoting positive body
      image?
AB  - This study evaluated the impact on young women's body satisfaction of an
      advertising campaign: Aerie Real, which included images of models who were not
      digitally modified. In total, 200 female students were randomly allocated to view
      either Aerie Real images or digitally modified images from previous campaigns. In
      the total sample, no condition differences appeared. However, participants with
      high appearance comparison reported a smaller decrease in body satisfaction after
      viewing the Aerie Real images as compared to those viewing previous images ( p =
      .003). Findings provide preliminary support for the Aerie Real campaign as less
      deleterious form of media for body image.

PMID- 27888255
TI  - Longitudinal analysis of intervention effects on temptations and stages of change
      for dietary fat using parallel process latent growth modeling.
AB  - The Dietary Guidelines for Americans recommend a 20-35 percent daily intake of
      fat. Resisting the temptation to eat high-fat foods, in conjunction with stage of
      readiness to avoid these foods, has been shown to influence healthy behavior
      change. Data ( N = 6516) from three randomized controlled trials were pooled to
      examine the relationships among direct intervention effects on temptations and
      stage of change for limiting high-fat foods. Findings demonstrate separate
      simultaneous growth processes in which baseline level of temptations, but not the
      rate of change in temptations, was significantly related to the change in
      readiness to avoid high-fat foods.

PMID- 27888256
TI  - Corrigendum.
AB  - Lubrini G, Rios Lago M, Perianez JA, et al. The contribution of depressive
      symptoms to slowness of information processing in relapsing remitting multiple
      sclerosis. Mult Scler 2016; 22: 1607-1615. DOI: 10.1177/1352458516661047 .

PMID- 27888257
TI  - A Flexible Question-and-Answer Task for Measuring Speech Understanding.
AB  - This report introduces a new speech task based on simple questions and answers.
      The task differs from a traditional sentence recall task in that it involves an
      element of comprehension and can be implemented in an ongoing fashion. It also
      contains two target items (the question and the answer) that may be associated
      with different voices and locations to create dynamic listening scenarios. A set
      of 227 questions was created, covering six broad categories (days of the week,
      months of the year, numbers, colors, opposites, and sizes). All questions and
      their one-word answers were spoken by 11 female and 11 male talkers. In this
      study, listeners were presented with question-answer pairs and asked to indicate
      whether the answer was true or false. Responses were given as simple button or
      key presses, which are quick to make and easy to score. Two preliminary
      experiments are presented that illustrate different ways of implementing the
      basic task. In the first experiment, question-answer pairs were presented in
      speech-shaped noise, and performance was compared across subjects, question
      categories, and time, to examine the different sources of variability. In the
      second experiment, sequences of question-answer pairs were presented amidst
      competing conversations in an ongoing, spatially dynamic listening scenario.
      Overall, the question-and-answer task appears to be feasible and could be
      implemented flexibly in a number of different ways.

PMID- 27888258
TI  - Forecasting the byproducts generated by hydrothermal carbonisation of municipal
      solid wastes.
AB  - The influences of temperature and residence times on the conversion and product
      distribution during hydrothermal carbonisation of municipal solid wastes were
      investigated. Analysis of variance and reaction severity were used to
      comprehensively analyse the experimental results. Analysis results showed both
      reaction temperature and residence time had varying degrees of impact on
      production distribution and hydrochars characteristic, while the effect of
      combine temperature and time was negligible. It is novel to find that the
      products yield was a linear function of the logarithm of the reaction ordinate.
      Base on comprehensive consideration, 240  degrees C to 260  degrees C and 50 min
      to 60 min would be the optimised reaction region to achieve relatively better
      economic benefits for hydrothermal carbonisation of municipal solid waste. By
      employing the analysis results and estimated models of high heating value and
      solid yield established in this article, predicting the product characteristics
      that have not been explored experimentally become possible.

PMID- 27888259
TI  - The disengaged in science communication: How not to count audiences and publics.
AB  - In this article, we suggest that three concepts from cultural and media studies
      might be useful for analysing the ways audiences are constructed in science
      communication: that media are immanent to society, media are multiple and
      various, and audiences are active. This article uses those concepts, along with
      insights from Science and Technology Studies (STS), to examine the category of
      'the disengaged' within science communication. This article deals with the
      contrast between 'common sense' and scholarly ideas of media and audiences in the
      field of cultural and media studies. It compares the 'common sense' with
      scholarly ideas of science publics from STS. We conclude that it may be time to
      reconsider the ontology of publics and the disengaged for science communication.

PMID- 27888260
TI  - Threshold concepts in prosthetics.
AB  - BACKGROUND: Curriculum documents identify key concepts within learning
      prosthetics. Threshold concepts provide an alternative way of viewing the
      curriculum, focussing on the ways of thinking and practicing within prosthetics.
      Threshold concepts can be described as an opening to a different way of viewing a
      concept. This article forms part of a larger study exploring what students and
      staff experience as difficult in learning about prosthetics. OBJECTIVES: To
      explore possible threshold concepts within prosthetics. STUDY DESIGN:
      Qualitative, interpretative phenomenological analysis. METHODS: Data from 18
      students and 8 staff at two universities with undergraduate prosthetics and
      orthotics programmes were generated through interviews and questionnaires. The
      data were analysed using an interpretative phenomenological analysis approach.
      RESULTS: Three possible threshold concepts arose from the data: 'how we walk',
      'learning to talk' and 'considering the person'. CONCLUSION: Three potential
      threshold concepts in prosthetics are suggested with possible implications for
      prosthetics education. These possible threshold concepts involve changes in both
      conceptual and ontological knowledge, integrating into the persona of the
      individual. This integration occurs through the development of memories
      associated with procedural concepts that combine with disciplinary concepts.
      Considering the prosthetics curriculum through the lens of threshold concepts
      enables a focus on how students learn to become prosthetists. Clinical relevance
      This study provides new insights into how prosthetists learn. This has
      implications for curriculum design in prosthetics education.

PMID- 27888261
TI  - Fluctuating residual limb volume accommodated with an adjustable, modular socket
      design: A novel case report.
AB  - BACKGROUND: This novel case report describes the problems of prescribing a
      prosthetic socket in a left transfemoral amputee secondary to chronic
      patellofemoral instability compounded by complex regional pain syndrome. Case
      Description and Methods: Following the amputation, complex regional pain syndrome
      symptoms recurred in the residual limb, presenting mainly with oedema. Due to
      extreme daily volume fluctuations of the residual limb, a conventional, laminated
      thermoplastic socket fitting was not feasible. Findings and Outcomes: An
      adjustable, modular socket design was trialled. The residual limb volume
      fluctuations were accommodated within the socket. Amputee rehabilitation could be
      continued, and the rehabilitation goals were achieved. The patient was able to
      wear the prosthesis for 8 h daily and to walk unaided indoors and outdoors.
      CONCLUSION: An adjustable, modular socket design accommodated the daily residual
      limb volume fluctuations and provided a successful outcome in this case. It
      demonstrates the complexities of socket fitting and design with volume
      fluctuations. Clinical relevance Ongoing complex regional pain syndrome symptoms
      within the residual limb can lead to fitting difficulties in a conventional,
      laminated thermoplastic socket due to volume fluctuations. An adjustable, modular
      socket design can accommodate this and provide a successful outcome.

PMID- 27888263
TI  - A CBPR Approach to Finding Community Strengths and Challenges to Prevent Youth
      Suicide and Substance Abuse.
AB  - PURPOSE: To improve health and reduce health disparities, research partnerships
      with American Indian and Alaska Native communities should build on existing
      traditions and strengths. The overall goal of this pilot project was to clarify
      the needs of tribal community members and determine strengths and resources
      available to the community. DESIGN: Community-based participatory research was
      the approach used to obtain community input. Data collection methods included,
      Photovoice ( n = 16), digital storytelling ( n = 4), and community capacity
      surveys ( n = 128). RESULTS: Quantitative and qualitative findings supported the
      need to (1) address youth suicide and substance abuse on the reservation and (2)
      use preexisting resources available in the community. The results led to the
      development of a strengths-based intervention incorporating the Gathering of
      Native American's curriculum. CONCLUSION: Integral to the development,
      implementation, and sustainability of the intervention was the truly reciprocal
      relationship developed between community and university partners.

PMID- 27888262
TI  - Search for an animal model to investigate selective pulmonary vasodilation.
AB  - Pulmonary arterial hypertension is a life-threatening disease with a poor
      prognosis. Oral treatment with vasodilators is often limited by systemic
      hypotension. Inhalation of vasodilators offers the opportunity for selective
      pulmonary vasodilation. Testing selective pulmonary vasodilation by inhaled
      nitric oxide or alternative substances in animal models requires an increased
      pulmonary vascular tone. The aim of this study was to identify animal models that
      are suitable for investigating selective pulmonary vasodilation. To do so, a
      haemodynamic stable pulmonary hypertension was initiated, with a 30 min duration
      deemed to be a sufficient time interval before and after a possible intervention.
      In anaesthetized and mechanically-ventilated Sprague-Dawley rats pulmonary
      hypertension was induced either by acute hypoxia due to reduction of the inspired
      oxygen fraction from 0.21 to 0.1 ( n = 6), a fixed infusion rate of the
      thromboxane analogue U46619 (240 ng/min; n = 6) or a monocrotaline injection
      (MCT; 60 mg/kg applied 23 days before the investigation; n = 7). The animals were
      instrumented to measure right ventricular and systemic arterial pressures. Acute
      hypoxia caused a short, and only transient, increase of pulmonary artery pressure
      as well as profound systemic hypotension which suggested haemodynamic
      instability. U46619 infusion induced variable changes in the pulmonary and
      systemic vascular tone without sufficient stabilization within 30 min. MCT
      provoked sustained pulmonary hypertension with normal systemic pressure values
      and inhalation of nitric oxide caused selective pulmonary vasodilation. In
      conclusion, out of the three examined rat animal models only MCT-induced
      pulmonary hypertension is a solid and reliable model for investigating selective
      pulmonary vasodilation.

PMID- 27888264
TI  - Sharing for Health: A Study of Chinese Adolescents' Experiences and Perspectives
      on Using Social Network Sites to Share Health Information.
AB  - PURPOSE: This exploratory qualitative study examines Chinese adolescents' health
      information sharing habits on social network sites. METHOD: Ten focus group
      meetings with 76 adolescents, ages 12 to 17 years, were conducted at community
      based organizations in Chicago's Chinatown. The research team transcribed the
      recording and analyzed the transcripts using ATLAS.ti. RESULTS: Chinese
      adolescents are using different social network sites for various topics of health
      information including food, physical activity, and so on. Adolescents would share
      useful and/or interesting health information. Many adolescents raised credibility
      concerns regarding health information and suggested evaluating the information
      based on self-experience or intuition, word-of-mouth, or information online.
      CONCLUSION: The findings shed lights on future intervention using social network
      sites to promote health among Chinese adolescents in the United States.
      IMPLICATIONS FOR PRACTICE: Future interventions should provide adolescents with
      interesting and culturally sensitive health information and educate them to
      critically evaluate health information on social network sites.

PMID- 27888265
TI  - Zika: exposing anew the need for health promotion in Latin America.

PMID- 27888269
TI  - Internal Carotid Artery Pseudoaneurysm and Ischemic Stroke Secondary to
      Retropharyngeal and Parapharyngeal Abscess.
AB  - Internal carotid artery pseudoaneurysm is an uncommon complication of
      retropharyngeal and parapharyngeal abscess in children. Treatment of the
      pseudoaneurysm has evolved in recent years from surgical ligation to endovascular
      techniques. Neurologic sequelae most commonly consist of Horner's syndrome with
      cerebral ischemia being uncommon. The clinical course of a 2-year-old boy with
      retropharyngeal abscess complicated by internal carotid artery pseudoaneurysm, is
      described and the literature is reviewed. A conventional angiogram confirmed the
      presence of a large pseudoaneurysm with no anterograde flow distal to the
      pseudoaneurysm and substantial collateral flow across the circle of Willis, with
      filling of the left anterior and middle cerebral arteries via the anterior and
      posterior communicating arteries. Endovascular occlusion resulted in nonfilling
      of the left internal carotid artery, pseudoaneurysm, and left internal jugular
      vein at the base of the skull. Following the procedure, the patient developed
      transient mild right hemiparesis associated with frontal lobe ischemia.

PMID- 27888270
TI  - Cerebellar Volume in Children With Attention-Deficit Hyperactivity Disorder
      (ADHD).
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is associated with altered
      cerebellar volume and cerebellum is associated with cognitive performance.
      However there are mixed results regarding the cerebellar volume in young patients
      with ADHD. To clarify the size and direction of this effect, we conducted the
      analysis on the large public database of brain images. The aim of this study was
      to confirm that cerebellar volume in ADHD is smaller than in control subjects in
      currently the largest publicly available cohort of ADHD subjects.We applied cross
      sectional case control study design by comparing 286 ADHD patients (61 female)
      with age and gender matched control subjects. Volumetric measurements of
      cerebellum were obtained using automated segmentation with FreeSurfer 5.1.
      Statistical analysis was performed in R-CRAN statistical environment. Patients
      with ADHD had significantly smaller total cerebellar volumes (134.5+/-17.11cm3
      vs.138.90+/-15.32 cm3). The effect was present in both females and males (males
      136.9+/-14.37 cm3 vs. 141.20+/-14.75 cm3; females 125.7+/-12.34 cm3 vs. 131.20+/
      15.03 cm3). Age was positively and significantly associated with the cerebellar
      volumes. These results indicate either delayed or disrupted cerebellar
      development possibly contributing to ADHD pathophysiology.

PMID- 27888271
TI  - Investigation of the Association Between Motor Stereotypy Behavior With
      Fundamental Movement Skills, Adaptive Functioning, and Autistic Spectrum Disorder
      Symptomology in Children With Intellectual Disabilities.
AB  - Motor stereotypy behaviors are patterned, coordinated, repetitive behaviors that
      are particularly evident in those with an autistic spectrum disorder and
      intellectual disabilities. The extent to which motor stereotypy behavior severity
      is associated with motor skills and maladaptive behavior, measures of adaptive
      functioning, along with fundamental movement skills and degree of autistic
      spectrum disorder symptomology is assessed in this preliminary report. Twelve
      participants, aged 7 to 16 years, with a reported motor stereotypy behavior and
      either mild or severe intellectual disability comprising developmental or global
      delay took part in the study. Spearman rho correlational analysis showed that
      severity of motor stereotypy behavior was significantly positively correlated
      with autistic spectrum disorder symptomology ( P = .008) and maladaptive behavior
      ( P = .008) but not fundamental movement skills ( P > .05). An increase in
      fundamental movement skills score was associated with a decrease in autistic
      spectrum disorder symptomology ( P = .01) and an increase in motor skills ( P =
      .002). This study provides evidence showing a significant relationship between
      motor stereotypy behavior severity with degree of autistic spectrum disorder
      symptomology and maladaptive behavior.

PMID- 27888272
TI  - Introductory paragraph.

PMID- 27888273
TI  - Upward ballooning of the third ventricle floor in a patient with slit ventricle
      syndrome: A unique magnetic resonance imaging finding.
AB  - Slit ventricle syndrome (SVS) is a well-known chronic complication of
      ventriculoperitoneal shunt (VPS) placement. In this report, we describe a unique
      anatomical change that we observed on the magnetic resonance (MR) images of the
      brain acquired from a patient with SVS. The patient was a 40-year-old woman who
      had undergone VPS placement at 3 months of age. A computed tomography scan of her
      brain revealed a slit-like ventricle. In addition, an MR image of her brain
      revealed upward ballooning of the third ventricle floor, which returned to normal
      after a lumbar puncture. This anatomical change resulted from the pressure
      gradient between the intra- and extraventricular spaces. We believe our findings
      will further our understanding of the pathogenesis of SVS. Moreover, we hope our
      findings will help clinicians to select endoscopic third ventriculostomy as the
      primary surgical approach in patients with this particular SVS pathogenesis in
      order to avoid complications.

PMID- 27888274
TI  - Percutaneous sacroplasty for the management of painful pathologic fracture in a
      multiple myeloma patient: Case report and review of the literature.
AB  - Percutaneous kyphoplasty has a well-established role in the treatment of
      pathologic fractures in patients with multiple myeloma. Despite this, there is a
      scarcity of literature surrounding its use and efficacy in the sacrum. We present
      a case of successful symptom resolution in a patient with painful sacral fracture
      following sacroplasty, and review the existing literature. An 81-year-man with
      multiple myeloma presented to the hematology/oncology clinic with a history of
      excruciating pain while seated. The impact of this pain on his quality of life
      subjectively was rated to be particularly high. Computed tomography of the sacrum
      confirmed the presence of pathologic fracture within the S1 and S2 vertebrae.
      Under fluoroscopic guidance, polymethyl methacrylate (PMMA) bone cement was
      injected via 11-gauge needles using an anterior-oblique approach. No immediate
      post-procedural complications occurred, such as foraminal extravasation or venous
      injection. The patient reported himself to be pain-free 1 day following the
      procedure, and this remains the case to date at 2 years of follow-up. Sacroplasty
      is technically feasible and can provide durable relief of symptoms in patients
      with painful pathologic fractures of the sacrum. It is likely underused and can
      offer tremendous benefit to myeloma patients.

PMID- 27888275
TI  - Acute disseminated encephalomyelitis following Campylobacter jejuni
      gastroenteritis: Case report and review of the literature.
AB  - We describe a case of a 25-year-old male with a diagnosis of acute disseminated
      encephalomyelitis (ADEM) following infection with Campylobacter jejuni, which is
      implicated in various human pathologies regarding the central nervous system
      (CNS) with acute course like Guillain-Barre syndrome (GBS), Miller-Fisher
      syndrome (MFS), Bickerstaff's brainstem encephalitis (BEE), acute transverse
      myelitis (ATM) as well as ADEM. These conditions are caused by cross-reactivity
      between Campylobacter's epitopes and cells of the CNS that causes an
      immunomediated inflammatory demyelination of the CNS. In the acute phase,
      magnetic resonance (MR) can detect pathologic signal intensity at the CNS with
      areas of pathologic contrast enhancement at cortical and spinal white matter that
      normalize over time or can be stable. These findings can be associated with edema
      in parts of the CNS. The lesions typically appear at different times during the
      disease course and also can have a different evolution. Our purpose therefore was
      to describe the clinical course and MR findings of this case and perform a
      critical review of the literature.

PMID- 27888276
TI  - Communicating About Choices in Transplantation (COACH).
AB  - INTRODUCTION: Previous research highlights the difficulties patients with end
      stage renal disease awaiting kidney transplant experience while attempting to
      manage both the logistical and the content-related aspects of discussions about
      transplantation. This article presents pilot results of the behavioral
      communication intervention program, Communicating about Choices in
      Transplantation (COACH), designed to improve transplant candidates' communication
      about transplantation. RESEARCH QUESTIONS: As compared to matched controls,
      increases in knowledge of deceased and living donor transplantation,
      communication self-efficacy, intentions to hold conversations about
      transplantation, and self-reported discussion were expected for pilot
      participants from pre- and postassessment; decreases in conversational
      difficulties were also posited. DESIGN: Using a nonrandomized quasi-experimental
      design, we compared transplant knowledge and communication between patients
      completing a 2-hour COACH session (pilot sample) to a sample of matched controls
      (n = 10). Data were collected via semi-structured telephone interviews upon
      enrollment and 1 month after enrollment or attendance at a COACH program session.
      RESULTS: The results revealed significant differences in knowledge from pre- to
      postassessment between the pilot and control samples ( P = .02). Although no
      other statistically significant between-group differences were found, paired
      sample t tests revealed significant pre-post increases in transplant knowledge
      (7.6 [standard deviation, SD = 2.0] to 9.5 [SD =1.8]; P = .05) and communication
      self-efficacy (1255.8 [SD = 239.7] to 1513.8 [SD = 114.3]; P = .009) for pilot
      participants. Decreases in perceived conversational difficulties were also
      observed ( P = .53). DISCUSSION: Results provide preliminary support for the
      program's impact. Moreover, participant evaluations of the COACH were
      overwhelmingly positive. A more definitive program evaluation with a larger, more
      diverse sample is currently underway.

PMID- 27888277
TI  - Looking the World in the Face: The Benefits and Challenges of Facial
      Transplantation for Blind Patients
AB  - Total bilateral blindness in the setting of facial transplantation is a
      controversial matter. Some transplant teams exclude these candidates, while
      others accept them onto their facial transplant waiting list. Using 3 cases, the
      clinical and ethical complexity of total bilateral blindness is explored.
      Guidance (medical, psychological, and social) for total bilateral blindness as
      both an inclusion and exclusion criterion is provided, with the stipulation that
      total bilateral blindness should not be an automatic exclusion criterion for
      facial transplantation. Additionally, guidance for corneal transplant in facial
      transplant candidates is discussed. Suggestions for posttransplant disability
      assistance for patients with total bilateral blindness are also provided.

PMID- 27888278
TI  - Missing Domains of Lung Transplant Patient Selection.
AB  - : The goal of consistent, predictable, and improved outcomes has continued to
      elude the scientific community in the 30 years since lung transplantation became
      the procedure of choice for patients with terminal, nonmalignant lung disease.
      BACKGROUND: Although there is consensus regarding disease-specific indications
      for lung transplant, ambiguity remains regarding how patient-specific attributes
      should influence lung transplant candidacy. This study had 3 aims (1) to
      establish the missing domains of the interdisciplinary assessment of the lung
      transplant candidate, (2) to have these domains validated by an international
      panel of lung transplant experts, and (3) to recommend the next step for
      inclusion of these domains into the lung transplant candidate selection process.
      METHODS: Three levels of evidence were reviewed. A search for standards and
      guidelines, a comprehensive literature review, and a validation of domains by
      experts were conducted. RESULTS: Seven domains of patient attributes were
      identified as relevant to lung transplant patient selection: cognitive
      performance, frailty, psychological factors, self-efficacy, social support,
      quality of life, and sociodemographic factors. Within each domain, several
      elements were identified to be incorporated in the process of patient assessment.
      CONCLUSION: Assessment of the missing domains and elements should be incorporated
      into the interdisciplinary lung transplant evaluation process. Standardized
      recognition and reporting of the patient-specific attributes will inform the work
      of individual transplant programs and the international transplant community.
      Further study is needed to associate these patient attributes with transplant
      outcomes. Improved understanding is needed regarding how nurses assess lung
      transplant candidates and how they communicate their findings within
      interdisciplinary settings.

PMID- 27888279
TI  - Predictors of Liver Transplant Patient Survival.
AB  - OBJECTIVE: Liver transplantation is a costly and risky procedure, representing 25
      050 procedures worldwide in 2013, with 6729 procedures performed in the United
      States in 2014. Considering the scarcity of organs and uncertainty regarding
      prognosis, limited studies address the variety of risk factors before
      transplantation that might contribute to predicting patient's survival and
      therefore developing better models that address a holistic view of transplant
      patients. This critical review aimed to identify predictors of liver transplant
      patient survival included in large-scale studies and assess the gap in risk
      factors from a holistic approach using the Wellbeing Model and the Strengthening
      the Reporting of Observational Studies in Epidemiology (STROBE) statement. DATA
      SOURCE: Search of the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), Medline, and PubMed from the 1980s to July 2014. STUDY SELECTION:
      Original longitudinal large-scale studies, of 500 or more subjects, published in
      English, Spanish, or Portuguese, which described predictors of patient survival
      after deceased donor liver transplantation. DATA EXTRACTION: Predictors were
      extracted from 26 studies that met the inclusion criteria. DATA SYNTHESIS: Each
      article was reviewed and predictors were categorized using a holistic framework,
      the Wellbeing Model (health, community, environment, relationship, purpose, and
      security dimensions). CONCLUSIONS: The majority (69.7%) of the predictors
      represented the Wellbeing Model Health dimension. There were no predictors
      representing the Wellbeing Dimensions for purpose and relationship nor emotional,
      mental, and spiritual health. This review showed that there is rigorously
      conducted research of predictors of liver transplant survival; however, the
      reported significant results were inconsistent across studies, and further
      research is needed to examine liver transplantation from a whole-person
      perspective.

PMID- 27888280
TI  - An Effective New Intestinal Anastomosis Method.
AB  - BACKGROUND This study aimed to establish an easy, safe, and cost-saving
      intestinal anastomotic method. MATERIAL AND METHODS Between January 2014 and
      February 2016, a total of 150 patients with gastric cancer who underwent surgery
      in the Department of General Surgery of Xuzhou Medical University Affiliated
      Hospital were divided into 2 groups: the treatment group (80) using new hand-sewn
      anastomoses, and the control group (70) using stapled anastomoses. Briefly, a new
      hand-sewn anastomosis of continuous suture without inversion was performed, with
      the first layer encompassing the entire layer of the intestinal wall. The edge
      was about 5 mm, and the stitch spacing was about 6 mm. Continuous suturing was
      performed only in the seromuscular layer of intestinal wall for the second layer,
      with the same edge and stitch spacing as the first layer. All 70 patients in the
      control group underwent intestinal stapled anastomoses. Surgical anastomotic time
      and cost, postoperative anastomotic bleeding, leakage, and stricture were
      recorded and analyzed. RESULTS The surgical anastomotic time using the new method
      was relatively short compared with the control group (8+/-1.6 min vs. 9+/-2.8
      min), and the cost of anastomosis using the new method was significantly lower
      compared to the control group ($30+/-6.8 vs. $1000+/-106.2). The new method
      exhibited lower anastomotic bleeding (0/80 vs. 2/70) and anastomotic leakage
      (0/80 vs. 1/70), but similar anastomotic stricture (0/80 vs. 0/70). CONCLUSIONS
      Our results suggest the new hand-sewn intestinal anastomosis is a safe, easy-to
      learn, cost-saving, and time-saving method that also avoids some of the drawbacks
      of the stapled anastomoses.

PMID- 27888281
TI  - The actions of relaxin family peptides on signal transduction pathways activated
      by the relaxin family peptide receptor RXFP4.
AB  - The relaxin family peptide receptor 4 (RXFP4) is a G protein-coupled receptor
      (GPCR) expressed in the colorectum with emerging roles in metabolism and appetite
      regulation. It is activated by its cognate ligand insulin-like peptide 5 (INSL5)
      that is expressed in enteroendocrine L cells in the gut. Whether other
      evolutionarily related peptides such as relaxin-2, relaxin-3, or INSL3 activate
      RXFP4 signal transduction mechanisms with a pattern similar to or distinct from
      INSL5 is still unclear. In this study, we compare the signaling pathways
      activated by various relaxin family peptides to INSL5. We found that, like INSL5,
      relaxin-3 activated ERK1/2, p38MAPK, Akt, and S6RP phosphorylations leading to
      increased cell proliferation and also caused GRK and beta-arrestin-mediated
      receptor internalization. Interestingly, relaxin-3 was slightly more potent than
      INSL5 in ERK1/2 and Akt phosphorylations, but both peptides were almost
      equipotent in adenylyl cyclase inhibition, S6RP phosphorylation, and cell
      proliferation. In addition, relaxin-3 showed greater efficacy only in Akt
      phosphorylation but not in the other pathways investigated. In contrast, no
      signaling activity or receptor internalization mechanisms were observed following
      relaxin-2 and INSL3. In conclusion, relaxin-3 is a high-efficacy agonist at RXFP4
      with a comparable signal transduction profile to INSL5.

PMID- 27888282
TI  - Monte Carlo systems used for treatment planning and dose verification.
AB  - General-purpose radiation transport Monte Carlo codes have been used for
      estimation of the absorbed dose distribution in external photon and electron beam
      radiotherapy patients since several decades. Results obtained with these codes
      are usually more accurate than those provided by treatment planning systems based
      on non-stochastic methods. Traditionally, absorbed dose computations based on
      general-purpose Monte Carlo codes have been used only for research, owing to the
      difficulties associated with setting up a simulation and the long computation
      time required. To take advantage of radiation transport Monte Carlo codes applied
      to routine clinical practice, researchers and private companies have developed
      treatment planning and dose verification systems that are partly or fully based
      on fast Monte Carlo algorithms. This review presents a comprehensive list of the
      currently existing Monte Carlo systems that can be used to calculate or verify an
      external photon and electron beam radiotherapy treatment plan. Particular
      attention is given to those systems that are distributed, either freely or
      commercially, and that do not require programming tasks from the end user. These
      systems are compared in terms of features and the simulation time required to
      compute a set of benchmark calculations.

PMID- 27888283
TI  - Retrograde conditioning of place preference and motor activity with cocaine in
      mice.
AB  - RATIONALE: In order to improve understanding of the nature of drug-associated
      memory, the current studies addressed whether conditioned place preference (CPP)
      could develop under conditions in which there was a delay between presentation of
      context and drug exposure (i.e., retrograde or trace conditioning). OBJECTIVES:
      The objective was to assess development of CPP when cocaine or methamphetamine
      was injected simultaneously with exposure to a salient context (S+), or after
      delays differing in length. METHODS: Dose response curves for conventional CPP
      were established using separate groups of Swiss-Webster mice injected with
      cocaine or methamphetamine just prior to S+ exposure. To assess the development
      of retrograde CPP, other groups received trace conditioning, where cocaine (15
      mg/kg) or methamphetamine (0.5 mg/kg) was injected after a delay of 15, 60, 120,
      180, 240, or 480 min following the end of the S+ session. RESULTS: Mice receiving
      conventional CPP with cocaine or methamphetamine during S+ showed significant
      place preference. None of the groups receiving delayed methamphetamine showed
      significant CPP; however, CPP was evident in mice receiving cocaine after delays
      of up to 4 h following S+. In a separate study, delayed methamphetamine also did
      not result in significant place preference when presented in doses of 0.25 or 1
      mg/kg. CONCLUSIONS: These results suggest that psychostimulant drug taking may be
      broadly generalized to context through retrograde association with events in
      recent memory, a factor that may contribute to drug-seeking and relapse following
      abstinence.

PMID- 27888284
TI  - Attenuation of the anxiogenic effects of cocaine by 5-HT1B autoreceptor
      stimulation in the bed nucleus of the stria terminalis of rats.
AB  - RATIONALE: Cocaine produces significant aversive/anxiogenic actions whose
      underlying neurobiology remains unclear. A possible substrate contributing to
      these actions is the serotonergic (5-HT) pathway projecting from the dorsal raphe
      (DRN) to regions of the extended amygdala, including the bed nucleus of the stria
      terminalis (BNST) which have been implicated in the production of anxiogenic
      states. OBJECTIVES: The present study examined the contribution of 5-HT signaling
      within the BNST to the anxiogenic effects of cocaine as measured in a runway
      model of drug self-administration. METHODS: Male Sprague-Dawley rats were fitted
      with bilateral infusion cannula aimed at the BNST and then trained to traverse a
      straight alley once a day for a single 1 mg/kg i.v. cocaine infusion delivered
      upon goal-box entry on each of 16 consecutive days/trials. Intracranial infusions
      of CP 94,253 (0, 0.25, 0.5, or 1.0 MUg/side) were administered to inhibit local 5
      HT release via activation of 5-HT1B autoreceptors. To confirm receptor
      specificity, the effects of this treatment were then challenged by co
      administration of the selective 5-HT1B antagonist NAS-181. RESULTS: Intra-BNST
      infusions of the 5-HT1B autoreceptor agonist attenuated the anxiogenic effects of
      cocaine as reflected by a decrease in runway approach-avoidance conflict
      behavior. This effect was reversed by the 5-HT1B antagonist. Neither start
      latencies (a measure of the subject's motivation to seek cocaine) nor spontaneous
      locomotor activity (an index of motoric capacity) were altered by either
      treatment. CONCLUSIONS: Inhibition of 5-HT1B signaling within the BNST
      selectively attenuated the anxiogenic effects of cocaine, while leaving
      unaffected the positive incentive properties of the drug.

PMID- 27888285
TI  - Efficacy of statins for osteoporosis: a systematic review and meta-analysis.
AB  - Our meta-analysis assessed the efficacy of statins on the risk of fracture, bone
      mineral density (BMD), and the markers of bone metabolism by collecting data from
      33 clinical trials. We found that statin treatment was associated with bone
      metabolism. And statins seemed to be more effective on male patients with
      osteoporosis. The efficacy of statins for the treatment of osteoporosis has been
      controversial in previous studies and meta-analyses. Our meta-analysis was
      conducted to examine in detail the efficacy of statins on osteoporosis. We
      searched PubMed, Embase, and the Cochrane Library databases for clinical trials
      from inception to May 2016. We included studies that described the effect of
      statins on the risk of fracture, BMD, or bone turnover markers. Moreover, we also
      conducted subgroup analyses according to the skeleton site, patient gender, and
      length of follow-up. A total of 33 studies which included 23 observational
      studies (16 cohort studies and 7 case-control studies) and 10 randomized
      controlled trials (RCTs) were evaluated. These 33 studies included 314,473
      patients in statin group and 1,349,192 patients in control group. Statins
      decreased the risk of overall fractures (OR = 0.81, 95% CI 0.73-0.89) and hip
      fractures (OR = 0.75, 95% CI 0.60-0.92). Furthermore, the use of statins was
      associated with increased BMD at the total hip (standardized mean difference
      (SMD) = 0.18, 95% CI 0.00-0.36) and lumbar spine (SMD = 0.20, 95% CI 0.07-0.32)
      and improved the bone formation marker, osteocalcin (OC) (SMD = 0.21, 95% CI 0.00
      0.42). However, there was no positive effect on vertebral fractures, upper
      extremity fractures, BMD at the femoral neck, bone-specific alkaline phosphatase
      (BALP), and serum C-terminal peptide of type I collagen (S-CTX). Also, compared
      with male subgroups, the effect on female subgroups was only slightly positive or
      of no statistical significance. Our meta-analysis indicates that statin treatment
      may be associated with a decreased risk of overall fractures and hip fractures,
      an increased BMD at the total hip, BMD at the lumbar spine, and OC. Moreover, our
      results also show that statin treatment may have a greater effect on male
      patients than on female patients.

PMID- 27888286
TI  - The effectiveness of a multidisciplinary hip fracture care model in improving the
      clinical outcome and the average cost of manpower.
AB  - : After the implementation of the multidisciplinary geriatric hip fracture
      clinical pathway in 2007, the hospital length of stay and the clinical outcomes
      improves. Moreover, the cost of manpower for each hip fracture decreases. It
      proves that this care model is cost-effective. INTRODUCTION: The objective of
      this study is to compare the clinical outcomes and the cost of manpower before
      and after the implementation of the multidisciplinary geriatric hip fracture
      clinical pathway (GHFCP). METHODS: The hip fracture data from 2006 was compared
      with the data of four consecutive years since 2008. The efficiency of the program
      is assessed using the hospital length of stay. The clinical outcomes include
      mortality rates and complication rates are compared. Cost of manpower was also
      analysed. RESULTS: After the implementation of the GHFCP, the preoperative length
      of stay shortened significantly from 5.8 days in 2006 to 1.3 days in 2011. The
      total length of stay in both acute and rehabilitation hospitals were also
      shortened by 6.1 days and 14.2 days, respectively. The postoperative pneumonia
      rate also decreased from 1.25 to 0.25%. The short- and long-term mortalities also
      showed a general improvement. Despite allied health manpower was increased to
      meet the increased workload, the shortened length of stay accounted for a mark
      decrease in cost of manpower per hip fracture case. CONCLUSION: This study proves
      that the GHFCP shortened the geriatric hip fracture patients' length of stay and
      improves the clinical outcomes. It is also cost-effective which proves better
      care is less costly.

PMID- 27888289
TI  - Epigenetic synergism between interleukin-4 and aryl-hydrocarbon receptor in human
      macrophages.
AB  - : The aryl hydrocarbon receptor (AhR)-ligand axis is involved in immune
      regulation, but its molecular basis remains to be fully elucidated. Chemokine (C
      C motif) ligand 1 (CCL1) is an important chemoattractant, but how CCL1 is
      regulated remains to be defined. The role of AhR in regulating CCL1 expression in
      two major subsets of macrophage was investigated. We used a human THP-1 cell
      line, monocytes, and mouse peritoneal macrophages to generate M(IFN-gamma/LPS)
      and M(IL-4) subsets, and the AhR's ligand effect was determined by the use of a
      combination of chromatin immunoprecipitation, PCR, and ELISA. Upon exposure to a
      classical AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), selective
      induction of CCL1 was noted only in M(IL-4), not M(IFN-gamma/LPS) cells in human
      but not murine macrophages. This selectivity was mediated by AhR's binding to the
      distal dioxin-responsive element (DRE) in the CCL1 promoter of the M(IL-4)
      subset, and a deletion mutant lacking the distal DRE sequence lost its activity.
      In contrast to the M(IFN-gamma/LPS) cells, the distal DRE was devoid of tri
      methylated histone 3 lysine 27 (H3K27) in M(IL-4) cells, and the addition of a
      H3K27 demethylase inhibitor blocked AhR-mediated CCL1 expression. Similar
      selectivity of CCL1 expression was also noted in monocyte-derived M(IL-4)
      subsets, and the level of AhR binding to distal DRE in monocytes was correlated
      with the levels of plasma interleukin-4 (IL-4) in 23 human subjects. These
      findings suggested the existence of a new regulatory epigenetic-based mechanism,
      wherein AhR in concert with IL-4 differentially regulated human, not murine,
      macrophage CCL1 response. KEY MESSAGE: Human CCL1 gene is selectively targeted by
      AhR in M(IL-4) macrophage. IL-4-induced epigenetic modification potentiates AhR
      mediated CCL1 expression. This epigenetic control of CCL1 expression is not
      operative in murine macrophages.

PMID- 27888290
TI  - [Influenza : How to vaccinate?]

PMID- 27888288
TI  - Nonlinear association of BMI with all-cause and cardiovascular mortality in type
      2 diabetes mellitus: a systematic review and meta-analysis of 414,587
      participants in prospective studies.
AB  - AIMS/HYPOTHESIS: The relationship between BMI and mortality has been extensively
      investigated in the general population; however, it is less clear in people with
      type 2 diabetes. We aimed to assess the association of BMI with all-cause and
      cardiovascular mortality in individuals with type 2 diabetes mellitus. METHODS:
      We searched electronic databases up to 1 March 2016 for prospective studies
      reporting associations for three or more BMI groups with all-cause and
      cardiovascular mortality in individuals with type 2 diabetes mellitus. Study
      specific associations between BMI and the most-adjusted RR were estimated using
      restricted cubic splines and a generalised least squares method before pooling
      study estimates with a multivariate random-effects meta-analysis. RESULTS: We
      included 21 studies including 24 cohorts, 414,587 participants, 61,889 all-cause
      and 4470 cardiovascular incident deaths; follow-up ranged from 2.7 to 15.9 years.
      There was a strong nonlinear relationship between BMI and all-cause mortality in
      both men and women, with the lowest estimated risk from 31-35 kg/m2 and 28-31
      kg/m2 (p value for nonlinearity <0.001) respectively. The risk of mortality at
      higher BMI values increased significantly only in women, whilst lower values were
      associated with higher mortality in both sexes. Limited data for cardiovascular
      mortality were available, with a possible inverse linear association with BMI
      (higher risk for BMI <27 kg/m2). CONCLUSIONS/INTERPRETATION: In type 2 diabetes,
      BMI is nonlinearly associated with all-cause mortality with lowest risk in the
      overweight group in both men and women. Further research is needed to clarify the
      relationship with cardiovascular mortality and assess causality and sex
      differences.

PMID- 27888287
TI  - Wnt signaling and cellular metabolism in osteoblasts.
AB  - The adult human skeleton is a multifunctional organ undergoing continuous
      remodeling. Homeostasis of bone mass in a healthy adult requires an exquisite
      balance between bone resorption by osteoclasts and bone formation by osteoblasts;
      disturbance of such balance is the root cause for various bone disorders
      including osteoporosis. To develop effective and safe therapeutics to modulate
      bone formation, it is essential to elucidate the molecular mechanisms governing
      osteoblast differentiation and activity. Due to their specialized function in
      collagen synthesis and secretion, osteoblasts are expected to consume large
      amounts of nutrients. However, studies of bioenergetics and building blocks in
      osteoblasts have been lagging behind those of growth factors and transcription
      factors. Genetic studies in both humans and mice over the past 15 years have
      established Wnt signaling as a critical mechanism for stimulating osteoblast
      differentiation and activity. Importantly, recent studies have uncovered that Wnt
      signaling directly reprograms cellular metabolism by stimulating aerobic
      glycolysis, glutamine catabolism as well as fatty acid oxidation in osteoblast
      lineage cells. Such findings therefore reveal an important regulatory axis
      between bone anabolic signals and cellular bioenergetics. A comprehensive
      understanding of osteoblast metabolism and its regulation is likely to reveal
      molecular targets for novel bone therapies.

PMID- 27888292
TI  - Seasonal and Spatial Variations of Saltmarsh Benthic Foraminiferal Communities
      from North Norfolk, England.
AB  - Time series foraminiferal data were obtained from samples collected from three
      sites at Brancaster Overy Staithe, Burnham Overy Staithe and Thornham on the
      North Norfolk coast over a 1-year period. At each collection point, six
      environmental variables-temperature, chlorophyll, sand, mud, pH and salinity-were
      also measured. The principle aim of this study was to examine the benthic
      foraminiferal fauna in regard to the temporal variability of foraminiferal
      abundance, seasonal trend, dominant species, species diversity and the impact of
      environmental variables on the foraminiferal communities in the top 1 cm of
      sediment over a 1-year time series. The foraminiferal assemblages at the three
      sites were dominated by three species: Haynesina germanica, Ammonia sp. and
      Elphidium williamsoni. Foraminiferal species showed considerable seasonal and
      temporal fluctuation throughout the year at the three investigated sites. The
      foraminiferal assemblage at the three low marsh zones showed a maximum abundance
      in autumn between September and November and a minimum abundance observed between
      July and August. There were two separate peaks in the abundance of Ammonia sp.
      and E. williamsoni, one in spring and another in autumn. In contrast, H.
      germanica showed a single peak in its abundance in autumn. A generalized additive
      modelling approach was used to explain the variation in the observed
      foraminiferal abundance and to estimate the significant impact of each of the
      environmental variables on living foraminiferal assemblages, with taxa abundance
      as the dependent variable. When included in the model as predictors, most of the
      environmental variables contributed little in explaining the observed variation
      in foraminiferal species abundance. However, the hypotheses for differences
      amongst sites, salinity and pH were significant and explained most of the
      variability in species relative abundance.

PMID- 27888291
TI  - Whole-Genome Enrichment Provides Deep Insights into Vibrio cholerae Metagenome
      from an African River.
AB  - The detection and typing of Vibrio cholerae in natural aquatic environments
      encounter major methodological challenges related to the fact that the bacterium
      is often present in environmental matrices at very low abundance in nonculturable
      state. This study applied, for the first time to our knowledge, a whole-genome
      enrichment (WGE) and next-generation sequencing (NGS) approach for direct
      genotyping and metagenomic analysis of low abundant V. cholerae DNA (<50 genome
      unit/L) from natural water collected in the Morogoro river (Tanzania). The
      protocol is based on the use of biotinylated RNA baits for target enrichment of
      V. cholerae metagenomic DNA via hybridization. An enriched V. cholerae metagenome
      library was generated and sequenced on an Illumina MiSeq platform. Up to 1.8 *
      107 bp (4.5* mean read depth) were found to map against V. cholerae reference
      genome sequences representing an increase of about 2500 times in target DNA
      coverage compared to theoretical calculations of performance for shotgun
      metagenomics. Analysis of metagenomic data revealed the presence of several V.
      cholerae virulence and virulence associated genes in river water including major
      virulence regions (e.g. CTX prophage and Vibrio pathogenicity island-1) and
      genetic markers of epidemic strains (e.g. O1-antigen biosynthesis gene cluster)
      that were not detectable by standard culture and molecular techniques. Overall,
      besides providing a powerful tool for direct genotyping of V. cholerae in complex
      environmental matrices, this study provides a 'proof of concept' on the
      methodological gap that might currently preclude a more comprehensive
      understanding of toxigenic V. cholerae emergence from natural aquatic
      environments.

PMID- 27888293
TI  - Cytokine-induced killer cells hunt individual cancer cells in droves in a mouse
      model.
AB  - Cytotoxicity of cytokine-induced killer (CIK) cells depends mainly on their
      encounters with target cells, but how many CIK cells are required to kill an
      individual cancer cell is unknown. Here we used time-lapse imaging to quantify
      the critical effector cell number required to kill an individual target cell. CIK
      cells killed MHC-I-negative and MHC-I-positive cancer cells, but natural killer
      (NK) cells destroyed MHC-I-negative cells only. The average threshold number of
      CIK cells required to kill an individual cancer cell was 6.7 for MHC-I-negative
      cells and 6.9 for MHC-I-positive cells. That of NK cells was 2.4 for MHC-I
      negative cells. Likely due to the higher threshold numbers, killing by CIK cells
      was delayed in comparison with NK cells: 40% of MHC-negative target cells were
      killed after 5 h when co-cultured with CIK cells and after 2 h with NK cells. Our
      data have implications for the rational design of CIK cell-based immunotherapy of
      cancer patients.

PMID- 27888294
TI  - Total hip arthroplasty with dual mobility cup in osteonecrosis of the femoral
      head in young patients: over ten years of follow-up.
AB  - Osteonecrosis of the femoral head affects mainly young patients with high
      functional needs this increases the risk of dislocation. Dual mobility cups known
      for low rate of dislocation and high mobility range seems indicated. We evaluate
      functional efficiency, survival and dislocation rate of dual mobility cup for
      total hip arthroplasty for osteonecrosis in young patients. Monocentric
      retrospective clinical study, from 2000 to 2008. With a clinical analysis in pre
      operative and over ten years of follow-up of one cohort of patients under 55
      years old with an indication of THA for ONFH. The judgement criteria was:
      clinical scores at the maximal follow-up, the dislocation rate, and the cumulate
      survival rate over ten years follow-up. Forty THA in 31 patients, nine bilateral
      cases, 23 males and eight females with average age of 44 (+/-4) years old. In pre
      operative: PMA 11 (+/-3.3), HHS 50,8 (+/-15.5). At the final follow-up of 129.8
      (+/-33.8) months: PMA (17.4 +/- 1.12), HHS (95.7 +/- 6.9), no dislocation. We had
      11 deaths on average at 95.2 +/- 47.3 months. The cumulate survival rate over ten
      years follow-up is 100% without revisions or long-term dislocation. Analysis
      concludes to very significant functional improvement without any dislocation
      despite the young population with high level of activity. Thus, dual mobility
      cups is a reliable choice preventing dislocation with a very good survival rate
      without premature wear, preserving mobility and activity.

PMID- 27888297
TI  - Elevated RON protein expression in endometriosis and disease-associated ovarian
      cancers.
AB  - BACKGROUND: Recepteur d'origine nantais (RON) protein expression has been
      demonstrated to correlate with tumor progression, metastasis, and prognosis, and
      its mRNA expression increases in deeply infiltrating endometriotic lesions.
      However, it remains unclear whether RON protein expression also increases in
      endometriotic lesions, and may be a risk factor of malignant transformation in
      endometriotic lesions. METHODS: The protein expression of RON in control (n =
      19), eutopic (n = 16), and ectopic (n = 51) endometria, as well as in
      endometriosis-associated ovarian cancers (EAOC, n = 16) was determined by
      immunohistochemical (IHC) staining. RESULTS: Endometriotic lesions expressed low
      levels of RON protein, but no RON protein expression appeared in matched eutopic
      or control endometrium. EAOC exhibited high levels of RON protein. The frequency
      and IHC score of RON protein expression were both significantly higher in EAOC
      [100.0% (14/14), 5.37 +/- 0.74] than those in endometriotic lesions [51.0%
      (26/51), 2.15 +/- 1.12; P = 0.002, 0.001]. Multivariate analysis of covariance
      only revealed a correlation of RON protein expression and EAOC (P = 0.006), but
      no correlations of RON protein expression and clinical parameters (P > 0.05).
      CONCLUSIONS: These obtained results suggest that increased RON expression might
      be involved in the pathogenesis of endometriosis and disease-associated ovarian
      cancers.

PMID- 27888296
TI  - Toll-like receptor 2 is increased in neurons in Parkinson's disease brain and may
      contribute to alpha-synuclein pathology.
AB  - Inflammation is likely a key contributor to the pathogenesis of Parkinson's
      disease (PD), a progressively debilitating neurodegenerative disease that is
      accompanied by a pathological accumulation of the alpha-synuclein protein in a
      staged manner through the brain. What leads to the accumulation of alpha
      synuclein in PD and how this relates to inflammatory pathways, however, is not
      entirely clear. Toll-like receptor (TLR) signaling is a major pathway mediating
      inflammation and, in particular, TLR2 is increasingly being implicated in PD. We
      have, therefore, examined the expression of TLR2 in postmortem brain tissue from
      PD patients and matched controls. We confirm that TLR2 is increased in PD brain,
      and find that levels of TLR2 correlate with the accumulation of pathological
      alpha-synuclein. TLR2 was expressed on neurons as well as microglia; however, the
      neuronal rather than glial expression of TLR2 was significantly increased in PD
      brain in accordance with disease staging, and TLR2 was strongly localized to
      alpha-synuclein positive Lewy bodies. In cell culture, activation of neuronal
      TLR2 induced an inflammatory response, including the secretion of inflammatory
      cytokines and microglial-activating chemokines, as well as the production of
      reactive oxygen species. Moreover, activation of neuronal TLR2 increased levels
      of endogenous alpha-synuclein protein, which was in turn associated with
      increased levels of the autophagy/lysosomal pathway marker p62. Finally,
      promoting autophagy with rapamycin or pharmacological inhibition of the TLR2
      signaling pathway prevented the TLR2-mediated increase in alpha-synuclein in
      neuronal cell cultures. These results implicate neuronal TLR2 expression in human
      PD pathogenesis. In particular, the increased expression of TLR2 on neurons may
      provide new insight into disease pathogenesis and/or options for therapeutic
      intervention.

PMID- 27888295
TI  - Platelet-rich plasma for the treatment of bone defects: from pre-clinical
      rational to evidence in the clinical practice. A systematic review.
AB  - PURPOSE: The treatment of large bone defects represents a significant challenge
      for orthopaedic surgeons. In recent years, biologic agents have also been used to
      further improve bone healing. Among these, platelet-rich plasma (PRP) is the most
      exploited strategy. The aim of the present study was to systematically review the
      available literature to identify: 1) preclinical in-vivo results supporting the
      rational of PRP use for bone healing; 2) evidence from the clinical practice on
      the actual clinical benefit of PRP for the treatment of fractures and
      complications such as delayed unions and non-unions. METHODS: A systematic review
      of the literature was performed on the application of PRP in bone healing, using
      the following inclusion criteria: pre-clinical and clinical reports of any level
      of evidence, written in English language, published in the last 20 years (1996
      2016), on the use of PRP to stimulate long-bone defect treatment, with focus on
      fracture and delayed/non-unions healing. RESULTS: The search in the Pubmed
      database identified 64 articles eligible for inclusion: 45 were preclinical in
      vivo studies and 19 were clinical studies. Despite the fact that the overall pre
      clinical results seem to support the benefit of PRP in 91.1 % of the studies, a
      more in depth analysis underlined a lower success rate, with a positive outcome
      of 84.4 % in terms of histological analysis, and even lower values considering
      radiological and biomechanical results (75.0 % and 72.7 % positive outcome
      respectively). This was also mirrored in the clinical literature, where the real
      benefit of PRP use to treat fractures and non-unions is still under debate.
      CONCLUSION: Overall, the available literature presents major limitations in terms
      of low quality and extreme heterogeneity, which hamper the possibility to
      optimize PRP treatment and translate it into a real clinical benefit despite
      positive preclinical findings on its biological potential to favour bone healing.

PMID- 27888298
TI  - ?

PMID- 27888299
TI  - ?

PMID- 27888300
TI  - Analysis of local recurrences after transanal endoscopic microsurgery for low
      risk rectal carcinoma.
AB  - AIM: Rates of local recurrence (LR) after transanal endoscopic microsurgery (TEM)
      for rectal carcinoma vary; the reasons remain unclear. We analyzed LR after TEM
      for low-risk pT1 (G1/2/X, L0/X) rectal carcinoma to investigate the influence of
      completeness of resection and occult lymph node metastasis on risk of LR. METHOD:
      LR location and stage, completeness of resection of primary carcinoma (minimal
      distance between tumor and resection line <=1 mm vs >1 mm), and incidence of
      involved lymph nodes in resected LR specimens were collected, and tumor
      characteristics of LR were compared with primary carcinoma. Distant metastasis
      and overall and cancer-specific survival were determined. RESULTS: LR developed
      in 14 patients; in 2/4 with R1/X resection, in 3/8 (38%) with clear margins (R0)
      but a minimal distance of <=1 mm, and in 9/88 (10%) with formally complete
      resection. Six of nine patients with formally complete resection underwent
      radical surgery for LR; in five out of these six, lymph nodes were not involved.
      In 5/14 patients, LR was poorly differentiated compared to primary carcinoma.
      Main LR causes were incomplete tumor resection or tumor persistence after
      formally complete resection. Overall (p = 0.008) and cancer-specific (p < 0.001)
      survival was lower in LR patients compared to non-LR patients, even if lymph
      nodes were uninvolved. CONCLUSIONS: The results suggest that most LRs after TEM
      for low-risk rectal cancer were caused by residual tumor at the previous excision
      site and not by undetected lymph node metastases. By improved standardization of
      surgical techniques to ensure complete resection of carcinomas and thorough
      pathological assessments, most LRs seem to be avoidable.

PMID- 27888302
TI  - [Macrophages : Causing ocular metastasis or immune reaction on tumor cells in the
      eye?]

PMID- 27888303
TI  - Dual-energy CT workflow: multi-institutional consensus on standardization of
      abdominopelvic MDCT protocols.
AB  - PURPOSE: To standardize workflow for dual-energy computed tomography (DECT)
      involving common abdominopelvic exam protocols. MATERIALS AND METHODS: 9
      institutions (4 rsDECT, 1 dsDECT, 4 both) with 32 participants [average # years
      (range) in practice and DECT experience, 12.3 (1-35) and 4.6 (1-14),
      respectively] filled out a single survey (n = 9). A five-point agreement scale
      (0, 1, 2, 3, 4-contra-, not, mildly, moderately, strongly indicated,
      respectively) and utilization scale (0-not performing and shouldn't; 1-performing
      but not clinically useful; 2-performing but not sure if clinically useful; 3-not
      performing it but would like to; 4-performing and clinically useful) were used.
      Consensus was considered with a score of >=2.5. Survey results were discussed
      over three separate live webinar sessions. RESULTS: 5/9 (56%) institutions
      exclude large patients from DECT. 2 (40%) use weight, 2 (40%) use transverse
      dimension, and 1 (20%) uses both. 7/9 (78%) use 50 keV for low and 70 keV for
      medium monochromatic reconstructed images. DECT is indicated for dual liver
      [agreement score (AS) 3.78; utilization score (US) 3.22] and dual pancreas in the
      arterial phase (AS 3.78; US 3.11), mesenteric ischemia/gastrointestinal bleeding
      in both the arterial and venous phases (AS 2.89; US 2.79), RCC exams in the
      arterial phase (AS 3.33; US 2.78), and CT urography in the nephrographic phase
      (AS 3.11; US 2.89). DECT for renal stone and certain single-phase exams is
      indicated (AS 3.00). CONCLUSIONS: DECT is indicated during the arterial phase for
      multiphasic abdominal exams, nephrographic phase for CTU, and for certain single
      phase and renal stone exams.

PMID- 27888301
TI  - The genome sequence and insights into the immunogenetics of the bananaquit
      (Passeriformes: Coereba flaveola).
AB  - Avian genomics, especially of non-model species, is in its infancy relative to
      mammalian genomics. Here, we describe the sequencing, assembly, and annotation of
      a new avian genome, that of the bananaquit Coereba flaveola (Passeriformes:
      Thraupidae). We produced ~30-fold coverage of the genome with an assembly size of
      ca. 1.2 Gb, including approximately 16,500 annotated genes. Passerine birds, such
      as the bananaquit, are commonly infected by avian malarial parasites
      (Haemosporida), which presumably drive adaptive evolution of immunogenetic loci
      within the host genome. In the context of our research on the distribution of
      avian Haemosporida, we specifically characterized immune loci, including toll
      like receptor (TLR) and major histocompatibility complex (MHC) genes.
      Additionally, we identified novel molecular markers in the form of single
      nucleotide polymorphisms (SNPs), both genome-wide and within identified immune
      loci. We discovered nine TLR genes and four MHC genes and identified five other
      TLR- or MHC- associated genes. Genome-wide, over 6 million high-quality SNPs were
      annotated, including 568 within TLR genes and 102 in MHC genes. This newly
      described genome and immune characterization expands the knowledge base for avian
      genomics and phylogenetics and allows for immune genotyping in the bananaquit,
      providing tools for the investigation of host-parasite coevolution.

PMID- 27888304
TI  - The wearable cardioverter-defibrillator in a real-world clinical setting:
      experience in 102 consecutive patients.
AB  - BACKGROUND: The wearable cardioverter-defibrillator (WCD) is used for temporary
      protection of patients deemed to be at high risk for sudden death (SCD) not yet
      meeting indications for the implantable defibrillator (ICD). OBJECTIVES: To
      evaluate the efficacy, safety, and compliance of/to WCD use and subsequent medium
      term outcome of patients in a single-center observational study. METHODS: A total
      of 102 consecutive patients were fitted with the WCD from 2012 to 2015 and
      followed for a mean of 11 months (+/-8 months). RESULTS: The most common clinical
      indication for WCD-prescription (63%) was a new diagnosis of severely impaired LV
      function (LVEF <=35%). The median wear time of the WCD was 54 days with a daily
      use of 23 h. Appropriate WCD therapy occurred in four patients (seven shocks for
      VF, one shock for VT). An ICD was finally implanted in 56 patients (55%).
      Improvement in LV function was the most common reason not to implant an ICD (HR
      0.37; 95% CI 0.19-0.73; p = 0.004). Two patients had inappropriate shocks from
      their WCD due to atrial fibrillation/flutter. Five patients fitted with an ICD
      after the end of WCD therapy suffered VT/VF episodes. After wearing the WCD, six
      patients died (five ICD recipients and one non-ICD recipient). CONCLUSION: WCD
      therapy was well accepted by patients and provided temporary protection against
      ventricular tachyarrhythmias in patients at risk for SCD. The WCD may help to
      avoid unnecessary ICD implantations in a significant proportion of patients.

PMID- 27888305
TI  - Reversed-phase separation methods for glycan analysis.
AB  - Reversed-phase chromatography is a method that is often used for glycan
      separation. For this, glycans are often derivatized with a hydrophobic tag to
      achieve retention on hydrophobic stationary phases. The separation and elution
      order of glycans in reversed-phase chromatography is highly dependent on the
      hydrophobicity of the tag and the contribution of the glycan itself to the
      retention. The contribution of the different monosaccharides to the retention
      strongly depends on the position and linkage, and isomer separation may be
      achieved. The influence of sialic acids and fucoses on the retention of glycans
      is still incompletely understood and deserves further study. Analysis of complex
      samples may come with incomplete separation of glycan species, thereby
      complicating reversed-phase chromatography with fluorescence or UV detection,
      whereas coupling with mass spectrometry detection allows the resolution of
      complex mixtures. Depending on the column properties, eluents, and run time,
      separation of isomeric and isobaric structures can be accomplished with reversed
      phase chromatography. Alternatively, porous graphitized carbon chromatography and
      hydrophilic interaction liquid chromatography are also able to separate isomeric
      and isobaric structures, generally without the necessity of glycan labeling.
      Hydrophilic interaction liquid chromatography, porous graphitized carbon
      chromatography, and reversed-phase chromatography all serve different research
      purposes and thus can be used for different research questions. A great advantage
      of reversed-phase chromatography is its broad distribution as it is used in
      virtually every bioanalytical research laboratory, making it an attracting
      platform for glycan analysis. Graphical Abstract Glycan isomer separation by
      reversed phase liquid chromatography.

PMID- 27888307
TI  - Monitoring doxorubicin cellular uptake and trafficking using in vitro Raman
      microspectroscopy: short and long time exposure effects on lung cancer cell
      lines.
AB  - Raman microspectroscopy is a non-invasive, in vitro analytical tool which is
      being increasingly explored for its potential in clinical applications and
      monitoring the uptake, mechanism of action and cellular interaction at a
      molecular level of chemotherapeutic drugs, ultimately as a potential label-free
      preclinical screening and companion diagnostic tool. In this study, doxorubicin
      (DOX), a "gold standard" chemotherapeutic drug, is employed as a model in the in
      vitro lung cancer cell line A549 in order to demonstrate the potential of Raman
      microspectroscopy to screen and identify spectroscopic markers of its trafficking
      and mechanism of action. Confocal laser scanning microscopy (CLSM) was used in
      parallel to illustrate the uptake and subcellular localisation, and cytotoxicity
      assays were employed to establish the toxicity profiles for early and late
      exposure times of A549 to DOX. Multivariate statistical analysis, consisting of
      principal components analysis (PCA), partial least squares regression (PLSR) and
      independent component analysis (ICA), was used to elucidate the spectroscopic
      signatures associated with DOX uptake and subcellular interaction. Raman
      spectroscopic profiling illustrates both drug kinetics and its pharmacodynamics
      in the cell and associated biochemical changes, demonstrating that DOX is mainly
      localised in the nuclear area, saturating the nucleolus first, within ~6 h of
      exposure, before the surrounding nuclear areas after ~12 h, and only accumulates
      in the cytoplasm after 48 h. PLSR over varying time intervals enables
      identification of DOX-DNA binding at early stages of exposure (0-12 h), while
      regression over longer time periods (24-72 h) reveals spectroscopic signatures
      associated with the metabolic cellular response. Graphical Abstract Subcellular
      uptake of doxorubicin, and changes in biomolecular signatures in the nucleolus,
      as monitored by Raman spectroscopy.

PMID- 27888306
TI  - A simple analytical method of determining 1-hydroxypyrene glucuronide in human
      urine by isotope dilution with ultra performance liquid chromatography-tandem
      mass spectrometry.
AB  - The glucuronide conjugate of 1-hydroxypyrene (1-OHP-G) is a sensitive and
      reliable index biomarker for assessing low exposure to polycyclic aromatic
      hydrocarbons (PAHs). A simple method for determining 1-OHP-G in human urine with
      ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was
      established and applied to evaluate the exposure level of PAHs of pregnant women
      in a large sample size. After the urine sample was extracted with ethyl acetate,
      0.2 mL of the aqueous phase was diluted to 1.0 mL with 5 mmol/L ammonium acetate
      before injection. The chromatographic separation was performed on a C18 column
      with a gradient elution and identification was conducted on a tandem mass
      spectrometry with electrospray ionization in negative mode. 1-OHP-d9-G was used
      as an internal standard to improve precision. The method was validated and good
      linearity was obtained in the range of 0.1~2.0 ng/mL. The limit of detection
      (LOD) and the limit of quantification (LOQ) of 1-OHP-G were 0.015 and 0.051
      ng/mL. Intra-day and inter-day precision were 4.3 and 6.7 %, respectively. The
      spiked recoveries were 79.4~106 % for urine samples. This method was rapid,
      sensitive, and very suitable for batch analysis of urine. Six hundred seventy
      five urine samples of pregnant women from the cities of Fuzhou, Shenzhen, and
      Nanning of P.R. China were analyzed with the proposed method. The medians of 1
      OHP-G concentration were 0.27 MUg/g.cr (n = 201), 0.30 MUg/g.cr (n = 212), and
      0.51 MUg/g.cr (n = 262) for the cities of Fuzhou, Shenzhen, and Nanning,
      respectively. 1-OHP-G concentrations in urine samples of pregnant women from the
      cities of Fuzhou and Shenzhen in coastal areas were both significantly lower than
      that of Nanning City in inland region (p < 0.001). Graphical Abstract The
      internal standard 1-OHP-d9-G and 2.0 mL of ethyl acetate were added to 1.0 mL of
      urine sample, after vortex vibration and centrifugation the aqueous phase was
      removed and diluted, and 5 MUl of aliquot was analyzed by UPLC-MS/MS.

PMID- 27888308
TI  - Comparative analysis of INLIGHTTM-labeled enzymatically depolymerized heparin by
      reverse-phase chromatography and high-performance mass spectrometry.
AB  - Structural characterization of the microheterogeneity of heparin, heparan
      sulfate, and other glycosaminoglycans is a major analytical challenge. We present
      the use of a stable isotope-labeled hydrazide tag (INLIGHTTM) with high
      resolution/accurate mass (HRAM) reverse-phase LC-MS/MS, which was recently
      introduced for detailed study of N-glycan heterogeneity, to characterize
      heparinase-digested heparin (digHep) products without the use of semi-volatile
      ion pairing reagents. Using both full scan LC-MS and data-dependent LC-MS/MS, we
      identified 116 unique digHep species, a feat possible because of INLIGHTTM
      labeling. Of these, 83 digHep products were structurally identified, including
      the 12 standard disaccharides as well as 34 tetra- (DP4), 26 hexa- (DP6), 21 octa
      (DP8), and 2 decasaccharides (DP10). Each of the 116 digHep species co-eluted
      with both light and heavy INLIGHTTM tags (L/Havg = 1.039 +/- 0.163); thus
      enhancing confidence in their identification via MS and MS/MS. This work sets the
      foundation for INLIGHTTM-based comparative analyses of different forms of
      heparin, heparan sulfate, and other GAGs with high quantitative precision using
      mainstay reverse-phase HRAM LC-MS/MS. Graphical Abstract Reducing end labeling
      strategy for mapping depolymerized heparin/heparan sulfate products by reverse
      phase LC-MS/MS.

PMID- 27888309
TI  - Selective quantification of DOSS in marine sediment and sediment-trap solids by
      LC-QTOF-MS.
AB  - At the onset of the 2010 Gulf oil spill, analytical methods for the
      quantification of the surfactants in Corexit did not exist in the peer-reviewed
      literature. To date, only a single study reports the presence of bis-(2
      ethylhexyl) sodium sulfosuccinate (DOSS) in deep-sea Gulf sediment collected in
      2010 from a single location. There are no data on the occurrence of DOSS in
      association with settling solids (i.e., sediment-trap solids). To address this
      data gap, DOSS was initially quantified by liquid chromatography tandem
      quadrupole mass spectrometry (LC-MS/MS) in sediment and sediment-trap solids
      collected from multiple sites in the Gulf between 2010 and 2013. However,
      interferences confounded analyses using only a quadrupole (MS/MS) system;
      therefore, a LC-high mass accuracy quadruple time of flight mass spectrometry (LC
      QTOF-MS) method was developed. The LC-QTOF method was validated and applied to
      eight representative samples of sediment and of sediment-trap solids. The
      presented method quantifies DOSS in solids of marine origin at concentrations
      above the limit of quantification of 0.23 MUg kg-1 with recoveries of 97 +/- 20 %
      (mean +/- 95 CI). Gulf sediment and sediment-trap solids gave DOSS concentrations
      of <LOQ-25 and 1.5-6.3 MUg kg-1, respectively. Graphical Abstract Sediment core
      and sediment trap materials were collected in the Gulf and analyzed for DOSS by
      LCQTOF.

PMID- 27888310
TI  - Determination of trace bisphenol A in environmental water by high-performance
      liquid chromatography using magnetic reduced graphene oxide based solid-phase
      extraction coupled with dispersive liquid-liquid microextraction.
AB  - Bisphenol A (BPA), an endocrine-disrupting chemical, has received much attention
      from researchers and the general public. In this paper, a novel method of
      determining BPA at trace levels was developed, using magnetic reduced graphene
      oxide (rGO-Fe3O4)-based solid-phase extraction coupled with dispersive liquid
      liquid microextraction (DLLME), followed by high-performance liquid
      chromatographic determination. The rGO-Fe3O4 was prepared and then characterized
      by Fourier transform infrared spectroscopy, transmission electron microscopy, and
      vibrating sample magnetometry. The greatest saturation magnetization of rGO-Fe3O4
      was up to 43.8 emu g-1, which allowed rapid isolation of the rGO-Fe3O4 from
      solutions upon applying an appropriate magnetic field. The effects of solution
      pH, adsorbent amount, type and volume of eluent and extraction solvent,
      extraction time, and salt concentration on the extraction efficiency of BPA were
      examined and optimized. Under the optimum conditions, an enrichment factor of
      5217 and an LOD of 0.01 MUg L-1 for BPA were obtained. The reusability of rGO
      Fe3O4 for at least 12 repeated cycles without any significant decrease in the
      extraction recovery of BPA was demonstrated. The proposed method was applied to
      the determination of BPA in different real water samples, with relative
      recoveries of 84.8-104.9 % and RSDs of 0.8-8.3 % in the spiked concentration
      range 1-10 MUg L-1.

PMID- 27888315
TI  - Thank you for 2016.

PMID- 27888311
TI  - Sampling and simultaneous determination of volatile per- and polyfluoroalkyl
      substances in wastewater treatment plant air and water.
AB  - Volatile per- and polyfluoroalkyl substances (PFASs) are often used as precursors
      in the synthesis of nonvolatile PFASs. The volatile PFASs, which include the
      perfluoroalkyl iodides (PFAIs), fluorotelomer iodides (FTIs), fluorotelomer
      alcohols (FTOHs), fluorotelomer olefins (FTOs), fluorotelomer acrylates (FTACs),
      and fluorotelomer methacrylates (FTMACs), are often produced starting from the
      telomerization process. These volatile compounds can be present in the air and
      water environment and can be transformed into highly persistent perfluoroalkyl
      carboxylic acids. With the exception of FTOHs, which are well studied, the
      determination of other volatile PFASs is also of prime importance in studying the
      sources and fate of PFASs. In this study, a method was developed to determine
      representative precursor compounds that included PFAIs, FTIs, FTOs, FTACs, and
      FTMACs in wastewater treatment plant (WWTP) air and water samples. The sampling
      and sample preparation step involved the use of solid-phase extraction (SPE)
      cartridges with HLBTM material to enrich the analyte. Gas chromatography with
      mass spectrometry was employed for the detection and quantification of the
      analytes. Method validation results showed high linearity and sensitivity in the
      positive electron ionization-selected ion monitoring mode (+EI-SIM). The absolute
      instrumental limits of detection were in the range of 0.5 to 2 pg. The method
      detection limit (MDL) in air was 1 ng/m3 with the exception of the FTACs which
      could be only be detected at concentrations higher than 40 ng/m3. The MDL in
      water was 10 ng/L. Direct spiking of the cartridges and analyte introduction by
      volatilization from the glass surface onto the SPE material had recoveries
      between 86 and 100%. The volatile PFASs were shown to readily partition into the
      air rather than into water. Consequently, large losses in the amount of PFASs
      were observed when these were spiked into the water. Graphical abstract
      Wastewater treatment plant air and water samples were passed through HLBTM solid
      phase materials. The eluates were injected onto a GC-MS system to simultaneously
      determine the volatile PFASs.

PMID- 27888314
TI  - Capillary coating as an important factor in optimization of the off-line and on
      line MEKC assays of the highly hydrophobic enzyme chlorophyllase.
AB  - The choice between bare and coated capillaries is a key decision in the
      development and use of any methods based on capillary electrophoresis. In this
      work several permanently and dynamically coated capillaries were successfully
      implemented in a previously developed micellar electrokinetic chromatography
      (MEKC) assay of the plant membrane enzyme chlorophyllase. The results obtained
      demonstrate the rationale behind the use of capillary coating, which is crucial
      for successful optimization of both the off-line mode and the on
      line/electrophoretically mediated microanalysis assay mode. The application of an
      amine permanently coated capillary (eCAP) is a simple way to significantly
      increase the repeatability of migration times and peak areas, and to ensure a
      strong electroosmotic flow that considerably decreases the overall analysis time.
      A dynamic coating (CEofix) allows one to apply an on-line incubation to control
      the reaction progress inside the capillary, and to increase the signal-to-noise
      ratio and peak efficiency. The dynamic coating is possible with use of both the
      normally applied uncoated silica capillary and the precoated amine capillary,
      which ensures more repeatable migration times. The strong points of the uncoated
      silica capillary are its attractive price and wide range of pH that can be
      applied. The characteristics presented may simplify the choice of capillary
      modification, especially in the case of hydrophobic analytes, MEKC-based
      separations, and other enzymatic assays.

PMID- 27888316
TI  - Erratum to: Treatment of patella baja by a modified Z-plasty.

PMID- 27888317
TI  - Effect of tibial slope changes on femorotibial contact kinematics after cruciate
      retaining total knee arthroplasty.
AB  - PURPOSE: The present study was undertaken to evaluate the effect of tibial slope
      (TS) changes on the femorotibial articular contact kinematics in subjects
      undergoing posterior cruciate-retaining total knee arthroplasty (CRTKA). METHODS:
      Eighteen knees in nine patients with medial osteoarthritis who underwent CRTKA
      using the same size prosthesis were analysed preoperatively and 2 years after
      TKA. TS changes were calculated on lateral radiographs taken before and after
      TKA. Knees were classified into two groups according to the change in TS obtained
      by subtracting the post-operative value from the preoperative value: group 1 (>3
      degrees ) and group 2 (<3 degrees ). The femorotibial articular contact
      kinematics of knees during weight-bearing flexion were compared between the two
      groups by two-dimensional/three-dimensional registration. RESULTS: Group 1 showed
      a continuous posterior translation of the medial femoral condyle during the
      process of knee flexion, whereas in group 2 the medial femoral condyle
      experienced paradoxical anterior motion from 20 degrees  to 90 degrees  of knee
      flexion. The lateral femoral condyle continuously moved posteriorly in both
      groups. CONCLUSION: A greater reduction in TS after TKA compared with
      preoperative TS reduces paradoxical medial femoral condylar movement. This may
      contribute to improved patient satisfaction after CR TKA. LEVEL OF EVIDENCE: III.

PMID- 27888319
TI  - Subacute cutaneous lupus erythematosus inducing unilateral sensorimotor
      neuropathy.
AB  - We describe the case of a 32-year-old male with previous history of subacute
      cutaneous lupus erythematosus (SCLE) who presented with arthritis followed by a
      unilateral lower-limb sensorimotor impairment, without biochemical or
      immunological marker abnormalities. Our patient currently satisfies only three of
      the systemic lupus international collaborating clinics criteria. Management of
      such patients is challenging due to lack of examples in the literature, with this
      case being the first described where a seronegative patient with SCLE
      demonstrated neurological involvement. A brief review of the available literature
      is included.

PMID- 27888318
TI  - Toward Improving the Fetal Diagnosis of Coarctation of the Aorta.
AB  - Coarctation of the aorta (CoA) is the most common ductal-dependent lesion missed
      on neonatal exam screening. Prenatal diagnosis of CoA improves outcomes through
      early initiation of prostaglandin. Fetal echocardiographic parameters including
      2D and Doppler findings have been studied as predictive measures for fetal
      diagnosis of CoA, but diagnosis rates remain variable. A comprehensive set of
      predictor variables was applied to fetuses suspected of CoA to analyze which
      parameters were associated with postnatal CoA. UCSF Fetal Cardiovascular Program
      databases were queried for fetuses suspected of CoA (2008-2014). Retrospective
      measurements of aorta/pulmonary artery ratio (AoPA), LV/RV ratio, ascending aorta
      Z-score (AscAo), isthmus Z-score, isthmus/duct ratio (I/D), posterior "shelf" of
      descending aorta, and diastolic flow persistence at the isthmus were recorded.
      ROC analysis identified the parameters most predictive of postnatal CoA. Among 97
      fetuses with probable CoA, 62 had complete follow-up. Of these fetuses, 45
      (72.5%) had postnatal confirmation of CoA and 17 did not have CoA. The parameters
      most predictive of postnatal CoA included AscAo, isthmus Z-score, and I/D, with
      respective AUC of 0.80, 0.89, and 0.90. Diastolic flow persistence was seen more
      often in fetuses with postnatal CoA, but did not reach statistical significance.
      Combining 2D and Doppler criteria (AoPA < 0.65 or diastolic flow persistence)
      improved sensitivity to 87%, but introduced several false positives. Isthmus
      imaging and AoPA ratio are useful predictors of CoA. Doppler information was most
      helpful when 2D imaging was equivocal; its addition resulted in high sensitivity
      in an enriched cohort referred for fetal echocardiography.

PMID- 27888321
TI  - Genetic characterization of canine parvovirus type 2 subtypes in Maputo,
      Mozambique.
AB  - Canine parvovirus type 2 (CPV-2) comprises three antigenic subtypes (2a, 2b and
      2c) that have been reported in many countries. These subtypes cause serious
      disease in dogs with characteristic gastroenteritis signs. Little information has
      been documented in Africa about the genetic characterization of CPV-2. The aim of
      this study was to detect and to characterize the CPV-2 subtypes circulating in
      dogs admitted to Veterinary Clinics from two cities of Mozambique, Maputo and
      Matola, in 2010. A total of 40 field fecal samples were collected and tested for
      CPV-2 by polymerase chain reaction assay. The partial length VP2 gene of the
      positive samples were sequenced and genetically analyzed. Twenty-six (65%) fecal
      samples were positive for CPV-2. The restriction fragment length polymorphism
      analysis was also performed from positive samples and did not reveal the presence
      of CPV-2c subtype. The results of the sequencing revealed the presence of CPV-2a
      (n = 9) and CPV-2b (n = 17). No CPV-2 and CPV-2c were detected. Sequence analysis
      comparison showed nucleotide identities of 99.6-100% among our CPV-2 isolates.
      Amino acid analysis showed predicted amino acid changes. Phylogenetically, all of
      the CPV-2a strains isolated formed a cluster together with South African and
      Nigerian isolates. Most of Mozambican CPV-2b isolates also tended to cluster
      together with South African isolates; however, four were more closely related to
      French strain and one isolates to the American strain. The present study was the
      first to characterize the CPV-2 circulating in the Mozambican dog population.

PMID- 27888322
TI  - Allee effect: the story behind the stabilization or extinction of microbial
      ecosystem.
AB  - A population exhibiting Allee effect shows a positive correlation between
      population fitness and population size or density. Allee effect decides the
      extinction or conservation of a microbial population and thus appears to be an
      important criterion in population ecology. The underlying factor of Allee effect
      that decides the stabilization and extinction of a particular population density
      is the threshold or the critical density of their abundance. According to Allee,
      microbial populations exhibit a definite, critical or threshold density, beyond
      which the population fitness of a particular population increases with the rise
      in population density and below it, the population fitness goes down with the
      decrease in population density. In particular, microbial population displays
      advantageous traits such as biofilm formation, expression of virulence genes,
      spore formation and many more only at a high population density. It has also been
      observed that microorganisms exhibiting a lower population density undergo
      complete extinction from the residual microbial ecosystem. In reference to Allee
      effect, decrease in population density or size introduces deleterious mutations
      among the population density through genetic drift. Mutations are carried forward
      to successive generations resulting in its accumulation among the population
      density thus reducing its microbial fitness and thereby increasing the risk of
      extinction of a particular microbial population. However, when the microbial load
      is high, the chance of genetic drift is less, and through the process of biofilm
      formation, the cooperation existing among the microbial population increases that
      increases the microbial fitness. Thus, the high microbial population through the
      formation of microbial biofilm stabilizes the ecosystem by increasing fitness.
      Taken together, microbial fitness shows positive correlation with the ecosystem
      conservation and negative correlation with ecosystem extinction.

PMID- 27888320
TI  - Cardiac mechanics and heart rate variability in patients with systemic sclerosis:
      the association that we should not miss.
AB  - We aimed to determine left ventricular (LV) and right ventricular (RV) structure,
      function and mechanics, as well as heart rate variability (HRV), and their
      relationship, in patients with systemic sclerosis (SSc). The study included 41
      SSc patients and 30 age-matched healthy volunteers. All the patients underwent
      clinical examination, serological tests, pulmonary function testing, 24-h Holter
      monitoring and complete two-dimensional echocardiography including strain
      analysis. The parameters of LV structure (interventricular septum thickness and
      LV mass index) and RV structure (RV wall thickness) were significantly higher in
      SSc patients. LV and RV diastolic function (estimated by mitral and tricuspid
      E/e' ratio) was significantly impaired in SSc group comparing with the healthy
      controls. LV and RV longitudinal function was significantly deteriorated in SSc
      patients. LV circumferential strain was also significantly lower in SSc group,
      whereas LV radial strain was similar between the observed groups. All parameters
      of time and frequency domain of HRV were decreased in SSc patients. LV and RV
      cardiac remodeling parameters, particularly diastolic function and longitudinal
      strain, were associated with HRV indices without regard to the main demographic
      or the clinical and echocardiographic characteristics. Rodnan Skin Score was also
      independently associated with biventricular cardiac remodeling in SSc patients.
      LV and RV structure, function and mechanics, as well as autonomic nervous
      function, were significantly impaired in SSc patients. There is the significant
      association between biventricular cardiac remodeling and autonomic function in
      these patients, which could be useful for their everyday clinical assessment.

PMID- 27888323
TI  - The calmodulin gene in Neurospora crassa is required for normal vegetative
      growth, ultraviolet survival, and sexual development.
AB  - We isolated a Neurospora crassa mutant of the calmodulin (cmd) gene using repeat
      induced point mutation and studied its phenotypes. The cmd RIP mutant showed a
      defect in growth, reduced aerial hyphae, decreased carotenoid accumulation, a
      severe reduction in viability upon ultraviolet (UV) irradiation, and a fertility
      defect. Moreover, meiotic silencing of the cmd gene resulted in a barren
      phenotype. In addition, we also performed site-directed mutational analysis of
      the calcium/calmodulin-dependent kinase-2 (Ca2+/CaMK-2), a target of the CaM
      protein encoded by the cmd gene. The camk-2 S247A and the camk-2 T267A mutants in
      a homozygous cross, or in a cross with a Deltacamk-2 mutant, displayed an
      intermediate phenotype, suggesting that serine 247 and threonine 267
      phosphorylation sites of the Ca2+/CaMK-2 are essential for full fertility in N.
      crassa. Therefore, CaM in N. crassa is required for normal vegetative growth, UV
      survival, and sexual development. Additionally, serine 247 and threonine 267
      phosphorylation sites are important for the Ca2+/CaMK-2 function.

PMID- 27888324
TI  - Learning to echolocate in sighted people: a correlational study on attention,
      working memory and spatial abilities.
AB  - Echolocation can be beneficial for the orientation and mobility of visually
      impaired people. Research has shown considerable individual differences for
      acquiring this skill. However, individual characteristics that affect the
      learning of echolocation are largely unknown. In the present study, we examined
      individual factors that are likely to affect learning to echolocate: sustained
      and divided attention, working memory, and spatial abilities. To that aim,
      sighted participants with normal hearing performed an echolocation task that was
      adapted from a previously reported size-discrimination task. In line with
      existing studies, we found large individual differences in echolocation ability.
      We also found indications that participants were able to improve their
      echolocation ability. Furthermore, we found a significant positive correlation
      between improvement in echolocation and sustained and divided attention, as
      measured in the PASAT. No significant correlations were found with our tests
      regarding working memory and spatial abilities. These findings may have
      implications for the development of guidelines for training echolocation that are
      tailored to the individual with a visual impairment.

PMID- 27888326
TI  - Secondary Sulfur and Nitrogen Species in PM10 from the Rijeka Bay Area (Croatia).
AB  - Samples of PM10 were collected over a 12 month period at two sites approximately
      5 km apart. Site 1 was an urban site in the center of the city of Rijeka,
      Croatia, and Site 2 was an industrial site in the proximity of a shipyard,
      located in the southeastwards direction from the city. No significant differences
      in airborne concentrations of PM10 or secondary inorganic ions were found between
      the two sites. Therefore, the sampling continued only at Site 1. The dominant
      airborne compound was ammonium sulfate, being approximately six times more
      abundant in the summer (S) months than ammonium nitrate. This ratio was lower in
      the winter (W) months, being approximately 1.5 at both sites. Seasonal
      distribution of secondary inorganic aerosols (SIA), particularly SO42- is
      emphasized in 2008-2009 with W/S <1, most likely caused by local emissions,
      meteorology and long-range transport. In spite of closing down the petroleum
      refinery facilities in mid-2008, no significant decline in airborne
      concentrations of sulfates, nitrates or ammonium were observed during the period
      from 2007 to 2009 at the site nearest to the refinery (Site 1).

PMID- 27888327
TI  - Pollution Assessment of Toxic and Potentially Toxic Elements in Agricultural
      Soils of the City Addis Ababa, Ethiopia.
AB  - Due to the significantly fast urban expansion and increased industrial
      activities, the soils in the farms in Addis Ababa are contaminated by some toxic
      and potentially toxic elements (As, V, Cr, Fe, Co, Ni, Cu, B, Ba, Sr, Zn, Mn, Pb
      and Cd) in varying degrees. The mean concentrations of Cr, Ni, As and B in most
      of the soil farms were found to be higher than the maximum recommended limits.
      The mean concentrations of Cd, Cu, Pb, Co, Ni and Mn were found to be higher than
      the background soil concentrations given for uncontaminated soils. Multivariate
      analyses coupled with correlation analysis were used to identify possible
      sources. The geo-accumulation index values for Cr, Mn and Pb indicated that the
      farm soils were unpolluted to moderately polluted as a result of anthropogenic
      activities. A comprehensive environmental management strategy should be
      formulated by the government to measure further pollution of the farmland soil.

PMID- 27888325
TI  - Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal
      cancer patients treated with regorafenib.
AB  - PURPOSE: This study was performed to evaluate whether fluorine-18
      fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT)
      could predict treatment outcome of regorafenib in metastatic colorectal cancer
      (mCRC). METHODS: Previously treated refractory mCRC patients were enrolled into a
      prospective biomarker study of regorafenib. For this sub-study, the results of
      FDG PET/CT scans at baseline and after two cycles of treatment were analyzed.
      Various metabolic parameters obtained from PET images were analyzed in relation
      to treatment outcome. RESULTS: A total of 40 patients were evaluable for PET
      image analysis. Among various PET parameters, total lesion glycolysis (TLG)
      measured in the same target lesions for RECIST 1.1 analysis were the most
      significant in predicting prognosis, with the lowest p-value observed in TLG
      calculated using the margin threshold of 40 % (TLG40 %). Further analysis using
      TLG40 % showed significantly longer overall survival (OS) in patients with lower
      baseline TLG40 % (<151.8) (p = 0.003, median 14.2 vs. 9.1 months in <151.8 and
      >=151.8, respectively). Patients showing higher decrease in TLG40 % after
      treatment showed significantly longer progression-free survival (PFS) (p = 0.001,
      median 8.0 vs. 2.4 months in %DeltaTLG40 % < -9.6 % and >= -9.6 %, respectively)
      and OS (p = 0.002, median 16.4 vs. 9.1 months in %DeltaTLG40 % < -9.6 % and >= 
      9.6 %, respectively). The same cutoff could discriminate patients with longer
      survival among the patients who were under the stable disease category according
      to RECIST 1.1 (median PFS 8.4 vs. 6.8 months, p = 0.020; median OS 18.3 vs. 11.5
      months, p = 0.049). CONCLUSION: Measurement of TLG can predict treatment outcome
      of regorafenib in mCRC.

PMID- 27888328
TI  - Potential of the Biotic Ligand Model (BLM) to Predict Copper Toxicity in the
      White-Water of the Solimoes-Amazon River.
AB  - In this study, we evaluated the capacity of the Biotic Ligand Model (BLM) to
      predict copper toxicity in white-waters of the Solimoes-Amazon River. LC50 tests
      using the species Otocinclus vittatus (Regan, 1904) were performed with Solimoes
      Amazon river water (100%) at 20%, 40%, 60%, and 80% dilutions. A sevenfold
      decrease in both dissolved and total Cu toxicity was observed in the experiment
      conducted with 100% when compared to 20% white-water, indicating that
      physicochemical characteristics of white-water attenuate Cu toxicity. There was
      agreement between the observed LC50 and the LC50 predicted by the BLM after the
      adjustment of critical accumulation concentration (LA50) for O. vittatus. BLM
      modeling indicated that dissolved organic carbon (DOC) and pH were the most
      important water parameters influencing Cu toxicity, followed by Ca2+. Our results
      highlight the first evidence that the BLM presents potential to predict Cu
      toxicity to aquatic organisms in the white-water of the Solimoes-Amazon River.

PMID- 27888329
TI  - The Origin of Hexavalent Chromium as a Critical Parameter for Remediation of
      Contaminated Aquifers.
AB  - Two different cases of Cr(VI) contaminated ophiolitic aquifers are presented
      herein. The first is located at Vergina (Northern Greece), where the maximum
      Cr(VI) concentration measured was 64 MUg/L, being one of the highest geogenic
      concentrations recorded globally in areas with similar geological background. The
      second case is located at Inofyta (Central Greece), a makeshift industrial area,
      where the maximum detected Cr(VI) concentration exceeds 10,000 MUg/L, indicating
      clearly anthropogenic activities as the main source. Although for the Vergina
      aquifer, area-wide institutional measures and in some cases pump and treat
      systems might be sufficient to ensure a safe water supply for domestic and
      agricultural use, this is not the case for the contaminated aquifer of Inofyta.
      There a comprehensive remediation scheme should be properly implemented adopting,
      however, realistic remediation targets, that should also take into account the
      geogenic contribution to the high Cr(VI) groundwater concentrations measured.

PMID- 27888333
TI  - Fusion of agarase and neoagarobiose hydrolase for mono-sugar production from
      agar.
AB  - In enzymatic saccharification of agar, endo- and exo-agarases together with
      neoagarobiose hydrolase (NABH) are important key enzymes for the sequential
      hydrolysis reactions. In this study, a bifunctional endo/exo-agarase was fused
      with NABH for production of mono-sugars (D-galactose and 3,6-anhydro-L-galactose)
      from agar using only one fusion enzyme. Two fusion enzymes with either
      bifunctional agarase (Sco3476) or NABH (Zg4663) at the N-terminus, Sco3476-Zg4663
      (SZ) and Zg4663-Sco3476 (ZS), were constructed. Both fusion enzymes exhibited
      their optimal agarase and NABH activities at 40 and 35  degrees C, respectively.
      Fusions SZ and ZS enhanced the thermostability of the NABH activity, while only
      fusion SZ showed a slight enhancement in the NABH catalytic efficiency (K cat/K
      M) from 14.8 (mg/mL)-1 s-1 to 15.8 (mg/mL)-1 s-1. Saccharification of agar using
      fusion SZ resulted in 2-fold higher mono-sugar production and 3-fold lower
      neoagarobiose accumulation when compared to the physical mixture of Sco3476 and
      Zg4663. Therefore, this fusion has the potential to reduce enzyme production
      cost, decrease intermediate accumulation, and increase mono-sugar yield in agar
      saccharification.

PMID- 27888330
TI  - Dendritic cells in central nervous system autoimmunity.
AB  - Dendritic cells (DCs) operate at the intersection of the innate and adaptive
      immune systems. DCs can promote or inhibit adaptive immune responses against
      neuroantigens. While DC intrinsic properties, i.e., their maturation state or the
      subset they belong to, are important determinants of the outcome of an autoimmune
      reaction, tissue-specific cues might also be relevant for the function of DCs.
      Thus, a better understanding of the performance of distinct DC subsets in
      specific anatomical niches, not only in lymphoid tissue but also in non-lymphoid
      tissues such as the meninges, the choroid plexus, and the inflamed CNS
      parenchyma, will be instrumental for the design of immune intervention strategies
      to chronic inflammatory diseases that do not put at risk basic surveillance
      functions of the immune system in the CNS. Here, we will review modern concepts
      of DC biology in steady state and during autoimmune neuroinflammation.

PMID- 27888334
TI  - Capacity of lactic acid bacteria in immunity enhancement and cancer prevention.
AB  - Lactic acid bacteria are associated with the human gastrointestinal tract. They
      are important for maintaining the balance of microflora in the human gut. An
      increasing number of published research reports in recent years have denoted the
      importance of producing interferon-gamma and IgA for treatment of disease. These
      agents can enhance the specific and nonspecific immune systems that are dependent
      on specific bacterial strains. The mechanisms of these effects were revealed in
      this investigation, where the cell walls of these bacteria were modulated by the
      cytokine pathways, while the whole bacterial cell mediated the host cell immune
      system and regulated the production of tumor necrosis factors and interleukins. A
      supplement of highly active lactic acid bacteria strains provided significant
      potential to enhance host's immunity, offering prevention from many diseases
      including some cancers. This review summarizes the current understanding of the
      function of lactic acid bacteria immunity enhancement and cancer prevention.

PMID- 27888335
TI  - Bayesian inference supports the host selection hypothesis in explaining adaptive
      host specificity by European bitterling.
AB  - Generalist parasites have the capacity to infect multiple hosts. The temporal
      pattern of host specificity by generalist parasites is rarely studied, but is
      critical to understanding what variables underpin infection and thereby the
      impact of parasites on host species and the way they impose selection on hosts.
      Here, the temporal dynamics of infection of four species of freshwater mussel by
      European bitterling fish (Rhodeus amarus) was investigated over three spawning
      seasons. Bitterling lay their eggs in the gills of freshwater mussels, which
      suffer reduced growth, oxygen stress, gill damage and elevated mortality as a
      result of parasitism. The temporal pattern of infection of mussels by European
      bitterling in multiple populations was examined. Using a Bernoulli Generalized
      Additive Mixed Model with Bayesian inference it was demonstrated that one mussel
      species, Unio pictorum, was exploited over the entire bitterling spawning season.
      As the season progressed, bitterling showed a preference for other mussel
      species, which were inferior hosts. Temporal changes in host use reflected
      elevated density-dependent mortality in preferred hosts that were already
      infected. Plasticity in host specificity by bitterling conformed with the
      predictions of the host selection hypothesis. The relationship between bitterling
      and their host mussels differs qualitatively from that of avian brood parasites.

PMID- 27888332
TI  - Interaction of gut microbiota with bile acid metabolism and its influence on
      disease states.
AB  - Primary bile acids serve important roles in cholesterol metabolism, lipid
      digestion, host-microbe interactions, and regulatory pathways in the human host.
      While most bile acids are reabsorbed and recycled via enterohepatic cycling, ~5%
      serve as substrates for bacterial biotransformation in the colon. Enzymes
      involved in various transformations have been characterized from cultured gut
      bacteria and reveal taxa-specific distribution. More recently, bioinformatic
      approaches have revealed greater diversity in isoforms of these enzymes, and the
      microbial species in which they are found. Thus, the functional roles played by
      the bile acid-transforming gut microbiota and the distribution of resulting
      secondary bile acids, in the bile acid pool, may be profoundly affected by
      microbial community structure and function. Bile acids and the composition of the
      bile acid pool have historically been hypothesized to be associated with several
      disease states, including recurrent Clostridium difficile infection, inflammatory
      bowel diseases, metabolic syndrome, and several cancers. Recently, however,
      emphasis has been placed on how microbial communities in the dysbiotic gut may
      alter the bile acid pool to potentially cause or mitigate disease onset. This
      review highlights the current understanding of the interactions between the gut
      microbial community, bile acid biotransformation, and disease states, and
      addresses future directions to better understand these complex associations.

PMID- 27888331
TI  - The origin of DCs and capacity for immunologic tolerance in central and
      peripheral tissues.
AB  - Dendritic cells (DCs) are specialized immune sentinels that play key role in
      maintaining immune homeostasis by efficiently regulating the delicate balance
      between protective immunity and tolerance to self. Although DCs respond to
      maturation signals present in the surrounding milieu, multiple layers of
      suppression also co-exist that reduce the infringement of tolerance against self
      antigens. These tolerance inducing properties of DCs are governed by their origin
      and a range of other factors including distribution, cytokines, growth factors,
      and transcriptional programing, that collectively impart suppressive functions to
      these cells. DCs directing tolerance secrete anti-inflammatory cytokines and
      induce naive T cells or B cells to differentiate into regulatory T cells (Tregs)
      or B cells. In this review, we provide a detailed outlook on the molecular
      mechanisms that induce functional specialization to govern central or peripheral
      tolerance. The tolerance-inducing nature of DCs can be exploited to overcome
      autoimmunity and rejection in graft transplantation.

PMID- 27888336
TI  - Ocean acidification alters temperature and salinity preferences in larval fish.
AB  - Ocean acidification alters the way in which animals perceive and respond to their
      world by affecting a variety of senses such as audition, olfaction, vision and pH
      sensing. Marine species rely on other senses as well, but we know little of how
      these might be affected by ocean acidification. We tested whether ocean
      acidification can alter the preference for physicochemical cues used for
      dispersal between ocean and estuarine environments. We experimentally assessed
      the behavioural response of a larval fish (Lates calcarifer) to elevated
      temperature and reduced salinity, including estuarine water of multiple cues for
      detecting settlement habitat. Larval fish raised under elevated CO2
      concentrations were attracted by warmer water, but temperature had no effect on
      fish raised in contemporary CO2 concentrations. In contrast, contemporary larvae
      were deterred by lower salinity water, where CO2-treated fish showed no such
      response. Natural estuarine water-of higher temperature, lower salinity, and
      containing estuarine olfactory cues-was only preferred by fish treated under
      forecasted high CO2 conditions. We show for the first time that attraction by
      larval fish towards physicochemical cues can be altered by ocean acidification.
      Such alterations to perception and evaluation of environmental cues during the
      critical process of dispersal can potentially have implications for ensuing
      recruitment and population replenishment. Our study not only shows that
      freshwater species that spend part of their life cycle in the ocean might also be
      affected by ocean acidification, but that behavioural responses towards key
      physicochemical cues can also be negated through elevated CO2 from human
      emissions.

PMID- 27888338
TI  - A comprehensively quantitative method of evaluating the impact of drought on crop
      yield using daily multi-scale SPEI and crop growth process model.
AB  - The quantitative evaluation of the impact of drought on crop yield is one of the
      most important aspects in agricultural water resource management. To assess the
      impact of drought on wheat yield, the Environmental Policy Integrated Climate
      (EPIC) crop growth model and daily Standardized Precipitation Evapotranspiration
      Index (SPEI), which is based on daily meteorological data, are adopted in the
      Huang Huai Hai Plain. The winter wheat crop yields are estimated at 28 stations,
      after calibrating the cultivar coefficients based on the experimental site data,
      and SPEI data was taken 11 times across the growth season from 1981 to 2010. The
      relationship between estimated yield and multi-scale SPEI were analyzed. The
      optimum time scale SPEI to monitor drought during the crop growth period was
      determined. The reference yield was determined by averaging the yields from
      numerous non-drought years. From this data, we propose a comprehensive
      quantitative method which can be used to predict the impact of drought on wheat
      yields by combining the daily multi-scale SPEI and crop growth process model.
      This method was tested in the Huang Huai Hai Plain. The results suggested that
      estimation of calibrated EPIC was a good predictor of crop yield in the Huang
      Huai Hai Plain, with lower RMSE (15.4 %) between estimated yield and observed
      yield at six agrometeorological stations. The soil moisture at planting time was
      affected by the precipitation and evapotranspiration during the previous 90 days
      (about 3 months) in the Huang Huai Hai Plain. SPEIG90 was adopted as the optimum
      time scale SPEI to identify the drought and non-drought years, and identified a
      drought year in 2000. The water deficit in the year 2000 was significant, and the
      rate of crop yield reduction did not completely correspond with the volume of
      water deficit. Our proposed comprehensive method which quantitatively evaluates
      the impact of drought on crop yield is reliable. The results of this study
      further our understanding why the adoption of counter measures against drought is
      important and direct farmers to choose drought-resistant crops.

PMID- 27888339
TI  - Nonlinear variations of forest leaf area index over China during 1982-2010 based
      on EEMD method.
AB  - Variations in leaf area index (LAI) are critical to research on forest ecosystem
      structure and function, especially carbon and water cycle, and their responses to
      climate change. Using the ensemble empirical mode decomposition (EEMD) method and
      global inventory modeling and mapping studies (GIMMS) LAI3g dataset from 1982 to
      2010, we analyzed the nonlinear feature and spatial difference of forest LAI
      variability over China for the past 29 years in this paper. Results indicated
      that the national-averaged forest LAI was characterized by quasi-3- and quasi-7
      year oscillations, which generally exhibited a rising trend with an increasing
      rate. When compared with 1982, forest LAI change by 2010 was more evident than
      that by 1990 and 2000. The largest increment of forest LAI occurred in Central
      and South China, while along the southeastern coastal areas LAI increased at the
      fastest pace. During the study period, forest LAI experienced from decrease to
      increase or vice versa across much of China and varied monotonically for only a
      few areas. Focusing on regional-averaged trend processes, almost all eco
      geographical regions showed continuously increasing trends in forest LAI with
      different magnitudes and speeds, other than tropical humid region and temperate
      humid/subhumid region, where LAI decreased initially and increased afterwards.

PMID- 27888337
TI  - Claudins: vital partners in transcellular and paracellular transport coupling.
AB  - Tight junction (TJ) strands between epithelial or endothelial cells are formed by
      claudins, a protein family comprising up to 27 members in mammals. Although many
      more proteins are involved in the formation of TJ complexes, claudins are the
      only TJ proteins that are able to form TJ-like strands when overexpressed in
      cells that are normally devoid of TJs (e.g., fibroblasts). Within the
      paracellular cleft, the extracellular domains of claudins provide the matrix that
      seals the paracellular pathway. However, within this matrix, some claudins act as
      channels that specifically allow certain ions to cross this barrier. Barrier
      forming claudins predominate in epithelia that enclose compartments containing
      harmful ion concentrations (e.g., H+ in the stomach, K+ in the inner ear
      endolymph) or high pressures (e.g., in blastocoel or brain ventricle formation
      during development). Here, even seemingly minor alterations in TJ composition may
      be detrimental to the organism. In contrast, in many transporting epithelia,
      channel-forming claudins are essential for transcellular and paracellular
      transport coupling. Mutation or knockout of channel-forming claudins in these
      tissues brings both transcellular and paracellular transports to a standstill.
      The present review will present examples to illustrate the importance of single
      members of the claudin family in general epithelial transport physiology.

PMID- 27888340
TI  - Prognostic value of comorbidities in patients with carcinoma of the major
      salivary glands.
AB  - This study aimed at evaluating the influence of comorbidities on outcome and
      survival in patients with carcinoma of the major salivary glands. Medical records
      of 109 patients with carcinoma of the major salivary glands treated at a single
      quaternary medical care and cancer center between 2003 and 2015 were reviewed.
      Comorbidities were classified according to the Age-Adjusted Charlson Comorbidity
      Index (ACCI) scoring system. 59 patients were males, 50 were females. Median age
      was 69 years and the median interval between tumor diagnosis and date of study
      inclusion was 71 months. Most carcinoma arose in the parotid gland (90 patients),
      and most patients presented with T 1 (25) or T 2 (37) cancer. Mean ACCI score was
      2.9, and the most frequent ACCI score was 4. Mean overall survival was 119 months
      (ACCI 0-3) and 55 months (ACCI score >4), respectively (p = 0.005). Mean disease
      free survival (ACCI 0-3) was 110 and 58 months (ACCI > 4), respectively (p =
      0.02). Survival was significantly improved in low grade tumors, lower T and UICC
      stage and lymph node-negative patients. Sex, age, history of smoking and
      resection margins had no influence on overall survival. High comorbidity is an
      independent risk factor on overall and disease-free survival in patients with
      major salivary gland carcinoma. This is the first study evaluating comorbidity
      using the ACCI scoring system in this group of patients.

PMID- 27888341
TI  - Efficacy of the transtemporal approach with awake brain mapping to reach the
      dominant posteromedial temporal lesions.
AB  - BACKGROUND: Surgeries for lesions in the dominant hippocampal and parahippocampal
      gyrus involving the posteromedial temporal regions are challenging to perform
      because they are located close to Wernicke's area; white matter fibers related
      with language; the optic radiations; and critical neurovascular structures. We
      performed a transtemporal approach with awake functional mapping for lesions
      affecting the dominant posteromedial temporal regions. The aim of this study was
      to assess the feasibility, safety, and efficacy of awake craniotomy for these
      lesions. METHODS: We retrospectively reviewed four consecutive patients with
      tumors or cavernous angiomas located in the left hippocampal and parahippocampal
      gyrus, which further extended to the posteromedial temporal regions, who
      underwent awake surgery between December 2014 and January 2016. RESULTS: Four
      patients with lesions associated with the left hippocampal and parahippocampal
      gyrus, including the posteromedial temporal area, who underwent awake surgery
      were registered in the study. In all four patients, cortical and subcortical
      eloquent areas were identified via direct electrical stimulation. This allowed
      determination of the optimal surgical route to the angioma or tumor, even in the
      language-dominant hippocampal and parahippocampal gyrus. In particular, this
      approach enabled access to the upper part of posteromedial temporal lesions,
      while protecting the subcortical language-related fibers, such as the superior
      longitudinal fasciculus. CONCLUSIONS: This study revealed that awake brain
      mapping can enable the safe resection of dominant posteromedial temporal lesions,
      while protecting cortical and subcortical eloquent areas. Furthermore, our
      experience with four patients demonstrates the feasibility, safety, and efficacy
      of awake surgery for these lesions.

PMID- 27888342
TI  - Putting recommendations into practice: Australian rheumatologists' opinions on
      leflunomide use in rheumatoid arthritis.
AB  - Leflunomide is the most recently introduced conventional disease-modifying anti
      rheumatic drugs in Australia. It has several unique methods for initiation,
      unique monitoring recommendations and a distinctive cessation protocol in the
      event of serious toxicity. The aim of this study was to evaluate initiation and
      monitoring practices of Australian rheumatologists using leflunomide. A survey
      was emailed twice, approximately 3 months apart to 332 rheumatologist members of
      the Australian Rheumatology Association. Wave analysis was used to assess
      evidence of non-response bias. The response rate to the survey was 20% and there
      was no difference between the responses of waves 1 and 2. Fifty percent of the
      respondents indicated that 20 mg once daily was the initial dose of leflunomide
      that they most commonly prescribed, 45% indicated 10 mg once daily, whilst only
      3% preferred to initiate leflunomide at 100 mg daily for 2-3 days followed by 10
      mg once a day as recommended when first marketed. Of the responders, 12% had used
      doses above 20 mg daily and 70% had used alternate daily dosing with leflunomide.
      In a patient taking leflunomide with an ALT or AST >3 times the ULN on two or
      more blood tests, 75% of responders indicated they would stop leflunomide
      immediately and 20% would follow cessation by administering a cholestyramine
      washout. The choice of initial leflunomide dose among responding Australian
      rheumatologists varied considerably, although most preferred not to use the
      loading dose. Despite the recommendation of clinical guidelines, the use of a
      cholestyramine washout procedure for hepatic toxicity is not universal.

PMID- 27888343
TI  - Laparoscopic anterior versus endoscopic posterior approach for adrenalectomy: a
      shift to a new golden standard?
AB  - PURPOSE: There has been an increased utilization of the posterior retroperitoneal
      approach (PRA) for adrenalectomy alongside the "classic" laparoscopic
      transabdominal technique (LTA). The aim of this study was to compare both
      procedures based on outcome variables at various ranges of tumor size. METHODS: A
      retrospective analysis was performed on 204 laparoscopic transabdominal (UMC
      Groningen) and 57 retroperitoneal (UMC Utrecht) adrenalectomies between 1998 and
      2013. We applied a univariate and multivariate regression analysis. Mann-Whitney
      and chi-squared tests were used to compare outcome variables between both
      approaches. RESULTS: Both mean operation time and median blood loss were
      significantly lower in the PRA group with 102.1 (SD 33.5) vs. 173.3 (SD 59.1)
      minutes (p < 0.001) and 0 (0-200) vs. 50 (0-1000) milliliters (p < 0.001),
      respectively. The shorter operation time in PRA was independent of tumor size.
      Complication rates were higher in the LTA (19.1%) compared to PRA (8.8%). There
      was no significant difference in recovery time between both approaches.
      CONCLUSIONS: Application of the PRA decreases operation time, blood loss, and
      complication rates compared to LTA. This might encourage institutions that use
      the LTA to start using PRA in patients with adrenal tumors, independent of tumor
      size.

PMID- 27888344
TI  - Impact of urgent resuscitative surgery for life-threatening torso trauma.
AB  - PURPOSE: This study investigated the advantages of performing urgent
      resuscitative surgery (URS) in the emergency department (ED); namely, our URS
      policy, to avoid a delay in hemorrhage control for patients with severe torso
      trauma and unstable vital signs. METHODS: We divided 264 eligible cases into a
      URS group (n = 97) and a non-URS group (n = 167) to compare, retrospectively, the
      observed survival rate with the predicted survival using the Trauma and Injury
      Severity Score (TRISS). RESULTS: While the revised trauma score and the injury
      severity score were significantly lower in the URS group than in the non-URS
      group, the observed survival rate was significantly higher than the predicted
      rate in the URS (48.5 vs. 40.2%; p = 0.038). URS group patients with a systolic
      blood pressure (SBP) <90 mmHg and a Glasgow coma scale (GCS) score of >=9 had
      significantly higher observed survival rates than predicted survival rates (0.433
      vs. 0.309, p = 0.008), (0.795 vs. 0.681, p = 0.004). The implementation of damage
      control surgery (DCS) was found to be a significant predictor of survival (OR
      5.23, 95% CI 0.113-0.526, p < 0.010). CONCLUSION: The best indications for the
      URS policy are an SBP <90 mmHg, a GCS >=9 on ED arrival, and/or the need for DCS.
      By implementing our URS policy, satisfactory survival of patients requiring
      immediate hemostatic surgery was achieved.

PMID- 27888346
TI  - Methionine and cysteine deficiencies altered proliferation rate and time-course
      differentiation of porcine preadipose cells.
AB  - Methionine (Met) is an essential sulfur amino acid (AA) limiting growth and is
      the precursor of cysteine (Cys), the rate-limiting factor in the synthesis of
      glutathione, and the main intracellular non-enzymatic antioxidant. This study
      aimed at determining the effects of limited supplies in Met and(or) Cys in early
      aspects of adipose tissue development and oxidative stress in differentiated
      adipocytes. Incremental reductions in Met (70, 40, and 0 uM) were compared with
      Met 100 uM (control dose) in porcine preadipocytes cultured in media without or
      with Cys (250 uM). In Cys-deprived media, both the absence (0 uM) and the lowest
      dose of Met (40 uM) reduced preadipocyte proliferation. Adding Cys in media only
      partly compensated for this decrease. On the opposite, mild Met deficiency (70
      uM) did not alter preadipocyte proliferation in media without or with Cys. Strong
      Met deficiency (40 uM) also reduced differentiation and lipid accumulation into
      preadipose cells. Mild Met deficiency also reduced preadipocyte differentiation
      when Cys was present in the culture media, whereas in Cys-deprived media, percent
      of differentiated cell was similar and intracellular lipid content was slightly
      higher at Met 70 uM than at Met 100 uM. Finally, incremental reductions in Met in
      media with or without Cys lowered reactive oxygen species (ROS) production by
      differentiated cells. These results demonstrate the strong dependency of porcine
      adipogenesis to sulfur AA supplies. Strong Met deficiency decreases both
      proliferation and differentiation, whereas mild deficiency only alters
      differentiation.

PMID- 27888345
TI  - Robust thalamic nuclei segmentation method based on local diffusion magnetic
      resonance properties.
AB  - The thalamus is an essential relay station in the cortical-subcortical
      connections. It is characterized by a complex anatomical architecture composed of
      numerous small nuclei, which mediate the involvement of the thalamus in a wide
      range of neurological functions. We present a novel framework for segmenting the
      thalamic nuclei, which explores the orientation distribution functions (ODFs)
      from diffusion magnetic resonance images at 3 T. The differentiation of the
      complex intra-thalamic microstructure is improved by using the spherical harmonic
      (SH) representation of the ODFs, which provides full angular characterization of
      the diffusion process in each voxel. The clustering was performed using the k
      means algorithm initialized in a data-driven manner. The method was tested on 35
      healthy volunteers and our results show a robust, reproducible and accurate
      segmentation of the thalamus in seven nuclei groups. Six of them closely matched
      the anatomy and were labeled as anterior, ventral anterior, medio-dorsal, ventral
      latero-ventral, ventral latero-dorsal and pulvinar, while the seventh cluster
      included the centro-lateral and the latero-posterior nuclei. Results were
      evaluated both qualitatively, by comparing the segmented nuclei to the
      histological atlas of Morel, and quantitatively, by measuring the clusters'
      extent and the clusters' spatial distribution across subjects and hemispheres. We
      also showed the robustness of our approach across different sequences and
      scanners, as well as intra-subject reproducibility of the segmented clusters
      using additional two scan-rescan datasets. We also observed an overlap between
      the path of the main long-connection tracts passing through the thalamus and the
      spatial distribution of the nuclei identified with our clustering algorithm. Our
      approach, based on SH representations of the ODFs, outperforms the one based on
      angular differences between the principle diffusion directions, which is
      considered so far as state-of-the-art method. Our findings show an anatomically
      reliable segmentation of the main groups of thalamic nuclei that could be of
      potential use in many clinical applications.

PMID- 27888347
TI  - Different phenotypes in identical twins with cerebrotendinous xanthomatosis: case
      series.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare, genetically determined error of
      metabolism. The characteristic clinical symptoms are diarrhea, juvenile
      cataracts, tendon xanthomas and neuropsychiatric alterations. The aim of this
      study is to present a pair of identical adult twins with considerable differences
      in the severity of phenotype. With regards to neuropsychiatric symptoms, the
      predominant features were severe Parkinsonism and moderate cognitive dysfunctions
      in the more-affected individual, whereas these alterations in the less-affected
      patient were only very mild and mild, respectively. The characteristic increase
      in the concentrations of serum cholestanol and the lesion volumes in dentate
      nuclei in the brain assessed with magnetic resonance imaging were quite similar
      in both cases. The lifestyle conditions, including eating habits of the twin
      pair, were quite similar as well; therefore, currently unknown genetic modifiers
      or certain epigenetic factors may be responsible for the differences in severity
      of phenotype. This case series serves as the first description of an identical
      twin pair with CTX presenting heterogeneous clinical features.

PMID- 27888348
TI  - Pathogenesis of COPD and Asthma.
AB  - Asthma and COPD remain two diseases of the respiratory tract with unmet medical
      needs. This review considers the current state of play with respect to what is
      known about the underlying pathogenesis of these two chronic inflammatory
      diseases of the lung. The review highlights why they are different conditions
      requiring different approaches to treatment and provides a backdrop for the
      subsequent chapters in this volume discussing recent advances in the pharmacology
      and treatment of asthma and COPD.

PMID- 27888350
TI  - Totally implantable vascular access device (TIVAD) placement: a modified
      technique that takes post-procedure aesthetic aspects into account.
AB  - Major progress has been made in breast cancer reconstruction surgery. The
      standard technique for totally implanted vascular access device (TIVAD)
      implantation generally requires an incision for port insertion on the anterior
      part of the thorax that leaves a scar in the middle of the neckline in patients
      who have undergone mastectomy with complex breast reconstruction. The aim of this
      technical note is to report our revised surgical technique for TIVAD placement.
      In patients with breast cancer, we take a lateralized approach, performing an
      oblique incision on the lowest part of the deltopectoral groove. This allows us
      to introduce the port and to place it on the anterolateral part of the thorax,
      thus avoiding an unaesthetic scar on the anterior part of the thorax. Our
      modified technique for TIVAD implantation is described.

PMID- 27888349
TI  - Final irrigation protocols may affect intraradicular dentin ultrastructure.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of different
      irrigation protocols on the root dentin structure using scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). MATERIALS AND
      METHODS: Thirty-nine lower bovine incisors were hemisected longitudinally and
      randomly divided into 13 groups (n = 3). After the root halves were reassembled,
      it was applied a specific irrigation protocol for each group, as following: G1,
      distilled water (control); G2, 0.9% saline; G3, saline + 17% EDTA; G4, saline +
      PUI; G5, saline + PUI + EDTA; G6 to G9 received the same protocol as above
      replacing 0.9% saline by 2.5% NaOCl; and G10 to G13 by 2% CHX. One-half of each
      sample was prepared and evaluated using SEM and the other one by TEM
      observations. RESULTS: TEM descriptive analysis showed modifications in dentin
      organic ultrastructure, characterized by the thinning of dentin collagen fibrils,
      caused by NaOCl, enhanced by EDTA and/or PUI. SEM analysis showed that NaOCl with
      PUI caused significantly larger erosion of the peritubular dentin than in all the
      other groups (P < 0.05), followed by NaOCl + EDTA and NaOCl + EDTA + PUI.
      CONCLUSIONS: NaOCl caused ultrastructural alterations in the dentin collagen, and
      enhanced by EDTA and/or PUI, promoted peritubular and intertubular erosion.
      CLINICAL RELEVANCE: The effect of irrigating solutions on dentin ultrastructure
      was still unclear. The acknowledgment about the kind of solution, concentrations,
      application time, and sequence of use was important to achieve the right
      sanitization without jeopardizing the dentin ultrastructure quality.

PMID- 27888352
TI  - Acknowledgment to referees.

PMID- 27888351
TI  - Identity, ecology and ecophysiology of planktic green algae dominating in ice
      covered lakes on James Ross Island (northeastern Antarctic Peninsula).
AB  - The aim of this study was to assess the phylogenetic relationships, ecology and
      ecophysiological characteristics of the dominant planktic algae in ice-covered
      lakes on James Ross Island (northeastern Antarctic Peninsula). Phylogenetic
      analyses of 18S rDNA together with analysis of ITS2 rDNA secondary structure and
      cell morphology revealed that the two strains belong to one species of the genus
      Monoraphidium (Chlorophyta, Sphaeropleales, Selenastraceae) that should be
      described as new in future. Immotile green algae are thus apparently capable to
      become the dominant primary producer in the extreme environment of Antarctic
      lakes with extensive ice-cover. The strains grew in a wide temperature range, but
      the growth was inhibited at temperatures above 20  degrees C, indicating their
      adaptation to low temperature. Preferences for low irradiances reflected the
      light conditions in their original habitat. Together with relatively high growth
      rates (0.4-0.5 day-1) and unprecedently high content of polyunsaturated fatty
      acids (PUFA, more than 70% of total fatty acids), it makes these isolates
      interesting candidates for biotechnological applications.

PMID- 27888353
TI  - Degenerative spondylolisthesis: contemporary review of the role of interbody
      fusion.
AB  - Degenerative spondylolisthesis is a common presentation, yet the best surgical
      treatment continues to be a matter of debate. Interbody fusion is one of a number
      of options, but its exact role remains ill defined. The aim of this study was to
      provide a contemporary review of the literature to help determine the role, if
      any, of interbody fusion in the surgical treatment of degenerative
      spondylolisthesis. A systematic review of the literature since 2005 was
      performed. Details on study size, patient age, surgical treatments, levels of
      slip, patient reported outcome measures, radiographic outcomes, complications and
      selected utility measures were recorded. Studies that compared a cohort treated
      with interbody fusion and at least one other surgical intervention for comparison
      were included for review. Only studies examining the effect in degenerative
      spondylolisthesis were included. Two authors independently reviewed the
      manuscripts and extracted key data. Thirteen studies were included in the final
      analysis. A total of 565 underwent interbody fusion and 761 underwent other
      procedures including decompression alone, interspinous stabilisation and
      posterolateral fusion with or without instrumentation. Most studies were graded
      Level III evidence. Heterogeneous reporting of outcomes prevented formal
      statistical analysis. However, in general, studies reviewed concluded no
      significant clinical or radiographic difference in outcome between interbody
      fusion and other treatments. Two small studies suggested interbody fusion is a
      better option in cases of definite instability. Interbody fusion only provided
      outcomes as good as instrumented posterolateral fusion. However, most studies
      were Level III, and hence, we remain limited in defining the exact role of
      interbody fusion-cases with clear instability appear to be most appropriate.
      Future work should use agreed-upon common outcome measures and definitions.

PMID- 27888354
TI  - Effects of reward and punishment on the interaction between going and stopping in
      a selective stop-change task.
AB  - Inhibition of no-longer relevant go responses supports flexible and goal-directed
      behavior. The present study explored if the interaction between going and
      stopping is influenced by monetary incentives. Subjects (N = 108) performed a
      selective stop-change task, which required them to stop and change a go response
      if a valid signal occurred, but to execute the planned go response if invalid
      signals or no signals occurred. There were two incentive groups: the punishment
      group lost points for unsuccessful valid-signal trials, whereas the reward group
      gained points for successful valid-signal trials. There was also a control group
      that could not win or lose points on any trials. We found that, compared with the
      control group, incentives encouraged subjects to slow down on no-signal trials,
      suggesting proactive control adjustments. Furthermore, latencies of valid change
      responses were shorter in the incentive groups than in the control group,
      suggesting improvements in executing an alternative response. However, incentives
      did not modulate stop latency or the interaction between going and stopping on
      valid-signal trials much. Finally, Bayesian analyses indicated that there was no
      difference between the reward and punishment groups. These findings are
      inconsistent with the idea that reward and punishment have distinct effects on
      stop performance.

PMID- 27888355
TI  - Psychometric properties of the Swedish version of the Treatment Outcome
      Satisfaction Questionnaire.
AB  - PURPOSE: Patient satisfaction is an outcome measure for low-back pain (LBP)
      interventions which allows clinicians to design patient-oriented treatments. The
      Treatment Outcome Satisfaction Questionnaire (TOSQ) is an English instrument
      constructed for such evaluations, and no equivalent instruments exist for the
      Swedish population. This study, therefore, translated TOSQ into Swedish and
      assessed the translated version's psychometric properties for patients with LBP.
      METHODS: A cross-cultural adaptation was used to translate TOSQ into Swedish.
      Subsequently, data from 131 patients with LBP whom undergone physiotherapy were
      consecutively aggregated and analyzed in a Rasch rating scale model with person
      measures standardized at 0-100 logits to evaluate the translated scale's
      validity. Finally, test-retest reliability of the Swedish version of TOSQ (TOSQ
      S) was quantified via an intraclass correlation coefficient (ICC) and the
      standard error of measurement (SEM) in 41 patients. RESULTS: TOSQ was
      successfully translated into Swedish; however, while some Rasch model indices
      supported the translated scale's unidimensionality, one out of eight items and 12
      out of 131 subjects misfitted the model. Scale optimization resulted in a 6-item
      subconfiguration, for which all items fitted the model, person misfits were
      reduced to ten subjects, and the person separation index increased from 1.86 to
      2.04. ICC and SEM estimates suggested acceptable reliability for the six-item
      TOSQ-S at 0.66 and 6.6 logits, respectively. CONCLUSIONS: A six-item TOSQ-S
      configuration showed acceptable psychometric properties and is suitable for
      measuring treatment outcome satisfaction of physiotherapy in patients with LBP.

PMID- 27888358
TI  - Veranstaltungen.

PMID- 27888356
TI  - Intestinal stem cell transplantation.
AB  - Organoid technologies to expand intestinal epithelial cells are gaining
      increasing attention as a useful tool to investigate many aspects of intestinal
      epithelial biology and pathology. One important application of organoid systems
      would be to use intestinal epithelial cells expanded in culture for following
      transplantation experiments. In this article, we present a brief overview of the
      studies that have succeeded in generating new epithelial tissues in the surface
      of native intestines in mice by organoid transplantation. We also discuss
      possible applications of this experimental approach in basic research on the
      intestinal epithelium as well as in regenerative medicine for various types of
      intestinal diseases in humans.

PMID- 27888357
TI  - Aberrant cytoplasmic expression of MHCII confers worse progression free survival
      in diffuse large B-cell lymphoma.

PMID- 27888360
TI  - Identification of symplasmic domains in the embryo and seed of Sedum acre L.
      (Crassulaceae).
AB  - MAIN CONCLUSION: Our study demonstrated that symplasmic communication between
      Sedum acre seed compartments and the embryo proper is not uniform. The presence
      of plasmodesmata (PD) constitutes the structural basis for information exchange
      between cells, and symplasmic communication is involved in the regulation of cell
      differentiation and plant development. Most recent studies concerning an analysis
      of symplasmic communication between seed compartments and the embryo have been
      predominantly performed on Arabidopsis thaliana. The results presented in this
      paper describe the analysis of symplasmic communication on the example of Sedum
      acre seeds, because the ultrastructure of the seed compartments and the embryo
      proper, including the PD, have already been described, and this species
      represents an embryonic type of development different to Arabidopsis. Moreover,
      in this species, an unusual electron-dense dome associated with plasmodesmata on
      the border between the basal cell/chalazal suspensor cells and the basal cell/the
      endosperm has been described. This prompted the question as to whether these
      plasmodesmata are functional. Thus, the aim of this study was to describe the
      movement of symplasmic transport fluorochromes between different Sedum seed
      compartments, with particular emphasis on the movement between the basal cell and
      the embryo proper and endosperm, to answer the following questions: (1) are seeds
      divided into symplasmic domains; (2) if so, are they stable or do they change
      with the development? The results have shown that symplasmic tracers movement:
      (a) from the external integument to internal integument is restricted; (b) from
      the basal cell to the other part of the embryo proper and from the basal cell to
      the endosperm is also restricted;

PMID- 27888362
TI  - Reply to the "Letter to the Editor" commenting on the article "An Update of
      Peripheral Ossifying Fibroma: Case Report and Literature Review".

PMID- 27888361
TI  - Morphological and structural characterization of the attachment system in aerial
      roots of Syngonium podophyllum.
AB  - MAIN CONCLUSION: The attachment of aerial roots of Syngonium podophyllum involves
      a multi-step process adjusted by multi-scale structures. Helical-crack root hairs
      are first found in the attachment system, representing specialized structures for
      surface anchorage. The morphological variability of attachment organs reflects
      diverse climbing strategies. One such anchoring mode in clinging-climbers
      involves the time-dependent interaction between roots and the support: By
      naturally occurring adhesive roots with root hairs, the plant can ascend on
      supports of any shape and size. As a typical root-climber, Syngonium podophyllum
      develops elongate aerial roots at nodes. Here, we studied its attachment behavior
      from the external morphology to the internal structure in detail. Through SEM and
      LM observation on several root-substrate interfaces, we suggested that the
      attachment of aerial roots was mediated by a multi-step process, in which root
      hairs played significant roles in releasing mucilaginous substance and securing
      the durable anchorage. We summarized all the types of shape changes of root hairs
      with particular focus on the abnormal transition from a tube to a helical-crack
      ribbon. We demonstrated our understanding with respect to the formation of the
      helical-crack root hairs, based on the structural evidence of cellulose
      microfibrils orientation on the cell wall lamellae. The helical-crack root hairs
      serving as energy-dissipating units retard the failure of adhesion under high
      winds and loads.

PMID- 27888359
TI  - Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with
      mortality in patients with liver cirrhosis.
AB  - BACKGROUND AND AIMS: Vitamin D deficiency is frequent in patients with cirrhosis.
      The aims of this study were to evaluate the relation of vitamin D status to
      portal hypertension, degree of liver dysfunction and survival. METHODS: Patients
      with cirrhosis who have been tested for 25-OH-vitamin D levels were
      retrospectively included. Vitamin D deficiency was defined as 25-OH-vitamin D
      levels <10 ng/ml. Child-Pugh score, model for end-stage liver disease (MELD) and
      available hepatic venous pressure gradient (HVPG) were recorded. Mortality was
      documented during follow-up. RESULTS: A total of 199 patients were included.
      Prevalence of vitamin D deficiency (<10 ng/ml) was 40% (79/199), with 14% in
      Child-Pugh stage A, 39% in Child-Pugh stage B and 47% in Child-Pugh stage C (p =
      0.001). Vitamin D deficiency was more common in patients with clinically
      significant portal hypertension (CSPH, HVPG >= 10 mm Hg) than in patients without
      (43.5% vs. 24.4%, p = 0.025). Significantly more deaths were observed in patients
      with vitamin D deficiency (32.9%, 26/79 vs. 13.3%, 16/120; p = 0.001). COX
      regression found presence of hepatocellular carcinoma (p < 0.001; HR: 5.763
      95%CI:2.183-15.213), presence of CSPH (p = 0.026; HR: 5.487 95%CI: 1.226-24.55)
      and Child-Pugh stage C (p = 0.003; HR:5.429 95%CI: 1.771-16.638) as independent
      risk factors for mortality. Furthermore we could show a tendency towards group
      vitamin D deficiency being an independent risk factor (p = 0.060; HR: 1.86
      95%CI:0.974-3.552). CONCLUSIONS: Vitamin D levels progressively decrease in more
      advanced Child stages and in patients with increasing HVPG. Vitamin D deficiency
      might be a valuable predictor of mortality in cirrhosis.

PMID- 27888363
TI  - Evaluation of the oropharynx in class I and II skeletal patterns by CBCT.
AB  - PURPOSE: This study aimed to evaluate the dimensions of the oropharynx and its
      shape in the minimum cross-sectional area, in individuals with Class I and Class
      II skeletal patterns, using three-dimensional CBCT images. METHODS: Forty-two
      cone-beam computed tomography images of grown individuals were evaluated. The
      images were divided according to the patient's skeletal patterns. The dimensions
      of the oropharyngeal airway space were determined using the Dolphin Imaging
      software. RESULTS: The volume and the minimum cross-sectional area were greater
      in patients with a Class I skeletal pattern, with a median difference of 5379 mm3
      and 86.8 mm2, respectively. The anteroposterior and lateral diameters in the
      minimum cross-sectional area were also higher in Class I individuals (2.3 and 6.0
      mm, respectively), but the ratio between them was not different. CONCLUSIONS: The
      volume and the minimum cross-sectional area of the oropharynx, as well as the
      anteroposterior and lateral diameters, are lower in individuals with a class II
      skeletal pattern than in individuals with a class I skeletal pattern. There was
      no difference in the shape of the oropharynx in healthy individuals with
      different skeletal patterns.

PMID- 27888364
TI  - In vitro reconstitution of the cyclosporine specific P450 hydroxylases using
      heterologous redox partner proteins.
AB  - The cytochrome P450 enzymes (CYPs) CYP-sb21 from Sebekia benihana and CYP-pa1
      from Pseudonocardia autotrophica are able to hydroxylate the immunosuppressant
      cyclosporin A (CsA) in a regioselective manner, giving rise to the production of
      two hair-stimulating agents (with dramatically attenuated immunosuppressant
      activity), gamma-hydroxy-N-methyl-L-Leu4-CsA (CsA-4-OH) and gamma-hydroxy-N
      methyl-L-Leu9-CsA (CsA-9-OH). Recently, the in vitro activity of CYP-sb21 was
      identified using several surrogate redox partner proteins. Herein, we
      reconstituted the in vitro activity of CYP-pa1 for the first time via a similar
      strategy. Moreover, the supporting activities of a set of ferredoxin
      (Fdx)/ferredoxin reductase (FdR) pairs from the cyanobacterium Synechococcus
      elongatus PCC 7942 were comparatively analyzed to identify the optimal redox
      systems for these two CsA hydroxylases. The results suggest the great value of
      cyanobacterial redox partner proteins for both academic research and industrial
      application of P450 biocatalysts.

PMID- 27888365
TI  - Development of a novel engineered antibody targeting Neisseria species.
AB  - OBJECTIVES: A Neissaria bacterial pilus sugar, bacillosamine, was synthesized
      and, for the first time, used as a probe to screen a single-chain variable
      fragment (scFv). RESULTS: Four Neisseria, Neisseria gonorrhoeae, Neisseria
      meningitidis, Neisseria sicca and Neisseria subflava, and two negative controls,
      Streptococcus pneumoniae and Escherichia coli, were tested through ELISA,
      immunostaining and gold nanoparticle immunological assay. All results indicated
      that the selected scFv is feasible for the specific detection of Neisseria
      species via the recognition of bacillosamine. CONCLUSIONS: The recombinant scFv
      could detect Neisseria strains at 106 CFU/ml.

PMID- 27888366
TI  - Heritability and Longitudinal Stability of Planning and Behavioral Disinhibition
      Based on the Porteus Maze Test.
AB  - The Porteus Maze Test (PMT) provides measures of planning and behavioral
      disinhibition. The PMT was administered to 941 twins during Wave 1 (9-10 years)
      and 320 twins during Wave 2 (11-13 years). Participants were drawn from the
      University of Southern California Risk Factors for Antisocial Behavior Study
      (RFAB). Heritability of behavioral disinhibition, determined by PMT Q-Score, were
      33% at Wave 1 and 52% at Wave 2. For planning, determined by Test Age,
      heritability was 53% at Wave 1; at Wave 2, the non-shared environment was
      important in boys, whereas genetic influences were important in girls. Both
      indices were modestly stable (r = 0.52; r = 0.37). A common genetic factor
      influenced both indices, respectively, at the two time points, with no 'new'
      genetic variance at Wave 2; the non-shared environment was time-specific. Thus,
      both genetic and non-shared environmental influences are important for behavioral
      disinhibition (Q-Score) and planning (Test Age).

PMID- 27888368
TI  - Primary Immunodeficiency Classification on Smartphone.

PMID- 27888367
TI  - Increasing Opportunities for Question-Asking in School-Aged Children with Autism
      Spectrum Disorder: Effectiveness of Staff Training in Pivotal Response Treatment.
AB  - Deficits in question-asking are common in children with autism spectrum disorder
      (ASD). Furthermore, their opportunities to self-initiate questions are often
      hindered by directive behavior of their conversation partners. This study
      assessed the effectiveness of staff training in pivotal response treatment (PRT)
      on staff member-created opportunities and self-initiated questions of school-aged
      children with ASD. Generalization and maintenance were also assessed.
      Participants were 14 staff members and children with ASD attending an inpatient
      treatment facility. Data showed that PRT resulted in significant increases in
      both staff member-created opportunities and child-initiated questions.
      Generalization to group situations and collateral changes in children's language,
      pragmatic, and adaptive skills, and maladaptive behaviors did not occur.
      Implications for clinical practice and directions for future research are
      discussed.

PMID- 27888369
TI  - Prevalence of periodontal pathogens as predictor of the evolution of periodontal
      status.
AB  - The aim of this study was to determine the relationship between the prevalence of
      Porphyromonas gingivalis, its fimA genotypes, Aggregatibacter
      actinomycetemcomitans, Tannerella forsythia, and Treponema denticola and the
      evolution of periodontal health. In a longitudinal prospective study, samples of
      subgingival plaque were taken from 114 patients (37 with chronic periodontitis,
      17 with gingivitis, and 60 periodontally healthy) in the course of a full
      periodontal examination. PCR was employed to determine the presence of the
      periodontopathogenic bacteria. Four years later, a second examination and sample
      collection were performed in 90 of these patients (20 with chronic periodontitis,
      12 with gingivitis, and 58 periodontally healthy). T. forsythia, P. gingivalis,
      and T. denticola are the most prevalent bacteria in patients with chronic
      periodontitis (78.4%, 62.2 y 56.8%, respectively). The P. gingivalis bacterium
      and its fimA genotypes I, II, and IV showed the highest correlation between the
      baseline and follow-up assessments. P. gingivalis fimA genotype II and T.
      forsythia were associated to a significant degree with unfavourable periodontal
      evolution. Of the variables studied, P. gingivalis fimA genotype II and T.
      forsythia increase the risk of an unfavourable evolution of periodontal status.

PMID- 27888370
TI  - Understanding the Impact of Migration on HIV Risk: An Analysis of Mexican
      Migrants' Sexual Practices, Partners, and Contexts by Migration Phase.
AB  - HIV risk among Mexican migrants varies across migration phases (pre-departure,
      transit, destination, interception, and return), but there is limited knowledge
      about specific sexual behaviors, characteristics of sexual partners, and sexual
      contexts at different migration stages. To fill the gap, we used data from a
      cross-sectional population-based survey conducted in Tijuana, Mexico. Information
      on migration phase and last sexual encounter was collected from 1219 male
      migrants. Our findings suggest that compared to pre-departure migrants, repeat
      migrants returning from communities of origin were more likely to have sex with
      male partners, use substances before sex, and not use condoms; migrants in the
      transit phase in the Mexican border were more likely to have sex with casual
      partners and sex workers; and migrants in the interception phase were more likely
      to engage in anal sex and use substances before sex. Sexual behaviors, partners,
      and contexts vary significantly among migrants at different migration phases.
      Tailored HIV prevention programs targeting Mexican migrants need to be developed
      and implemented at all migration phases.

PMID- 27888372
TI  - Effect of oil pollution on function of sandy soils in protected deserts and
      investigation of their improvement guidelines (case study: Kalmand area, Iran).
AB  - Soil pollution is one of the most dangerous sorts of environmental pollutions
      because of waste materials, fossil fuels, etc. Unfortunately in developing
      countries, there are very few arrangements to prevent soil pollution due to the
      fossil fuels and to improve polluted soil. In this research, influences of gas
      oil on properties of Kalmand protected area's sandy soil near Yazd, Iran, were
      studied. It was found that gas oil constituted 5.25% of soil weight in the
      refueling station in the region. Therefore, cleaning and strengthening of the
      soil by adding cement rather than expensive and complicated methods were the most
      important goals of this research. First, the influence of gas oil on soil
      properties was studied, and to improve the soil, different percentages of
      ordinary portland cement were added to the polluted sand to study the improved
      soil properties using laboratory tests. It was found that unconfined compressive
      strength, cohesion, and angle of internal friction of sample with 16% cement and
      8% gas oil after 28 days of curing were higher than those of the specimen of 6%
      cement and 14% gas oil, at 4.6, 5.4, and 1.3 times, respectively. Moreover, based
      on falling head tests it was observed that permeability of the stabilized
      specimens decreased substantially. From SEM tests, fewer voids were observed in
      the stabilized samples, which led to less pollutant penetration into the soil.
      According to EDX, although dangerous elements in the contaminated specimen made
      up 3.99% of the specimen total weight, addition of cement introduced considerable
      amounts of elements that are vital for pozzolanic reactions. Therefore, it can be
      concluded that addition of cement to the gas oil-polluted soil not only can
      improve geotechnical properties of the soil and reduce its permeability, but also
      is very efficient for environmental issues.

PMID- 27888374
TI  - Prophylactic mechanical hemodynamic support for catheter ablation of VT: locking
      the barn door before the horse has bolted.

PMID- 27888371
TI  - Protective Effect of the Sulfated Agaran Isolated from the Red Seaweed Laurencia
      aldingensis Against Toxic Effects of the Venom of the Snake, Lachesis muta.
AB  - Snakebite is a serious occupational hazard affecting mainly rural populations of
      tropical and subtropical developing countries. Lachesis muta (Bushmaster) bites
      are extremely serious but are rarely reported in the literature. Bushmaster
      envenomings are characterized by intense local pain, edema, neurotoxicity,
      hypotension, local hemorrhage, and dramatic systemic alterations. Antivenom
      treatment has regularly been used for more than a century; however, it fails to
      neutralize local tissue damage and hemorrhage, leading to morbidity or
      disabilities in victims. Thus, the production and clinical use of antivenom must
      be improved. The present work characterizes, for the first time, a sulfated
      polysaccharide from the red seaweed, Laurencia aldingensis, including its
      neutralizing effect on some toxic activities of L. muta venom. Chemical and
      spectroscopic analyses showed that L. aldingensis produces sulfated agarans with
      the A-units partially C-2 sulfated or 6-O-methoxylated presetting the B-units in
      the cyclized (3,6-anhydro-alpha-L-galactose) or in the non-cyclized form (alpha-L
      galactose). The latter is significantly substituted by sulfate groups on C-6. In
      vitro and in vivo assays showed that this sulfated agaran inhibited hemolysis,
      coagulation, proteolysis, edema, and hemorrhage of L. muta venom. Neutralization
      of hemorrhagic activity was also observed when the agaran was administered by
      different routes and after or before the venom injection. Furthermore, the agaran
      blocked the edema caused by a phospholipase A2 isolated from the L. muta venom.
      Experimental evidence therefore indicates that the sulfated agaran of L.
      aldingensis has potential to aid antivenom therapy of accidents caused by L. muta
      venom and may help to develop more effective antivenom treatments of snake bites
      in general.

PMID- 27888373
TI  - Combined toxic effect of airborne heavy metals on human lung cell line A549.
AB  - Many studies have demonstrated that heavy metals existing as a mixture in the
      atmospheric environment cause adverse effects on human health and are important
      key factors of cytotoxicity; however, little investigation has been conducted on
      a toxicological study of a metal mixture from atmospheric fine particulate
      matter. The objective of this study was to predict the combined effects of heavy
      metals in aerosol by using in vitro human cells and obtain a suitable mixture
      toxicity model. Arsenic, nickel, and lead were selected for mixtures exposed to
      A549 human lung cancer cells. Cell proliferation (WST-1), glutathione (GSH), and
      interleukin (IL)-8 inhibition were observed and applied to the prediction models
      of mixture toxicity, concentration addition (CA) and independent action (IA). The
      total mixture concentrations were set by an IC10-fixed ratio of individual
      toxicity to be more realistic for mortality and enzyme inhibition tests. The
      results showed that the IA model was statistically closer to the observed results
      than the CA model in mortality, indicating dissimilar modes of action. For the
      GSH inhibition, the results predicted by the IA and CA models were highly
      overestimated relative to mortality. Meanwhile, the IL-8 results were stable with
      no significant change in immune reaction related to inflammation. In conclusion,
      the IA model is a rapid prediction model in heavy metals mixtures; mortality, as
      a total outcome of cell response, is a good tool for demonstrating the combined
      toxicity rather than other biochemical responses.

PMID- 27888375
TI  - HBK-14 and HBK-15 with antidepressant-like and/or memory-enhancing properties
      increase serotonin levels in the hippocampus after chronic treatment in mice.
AB  - 5-HT1A and 5-HT7 receptor ligands might have antidepressant-like properties and
      improve cognitive function. We previously reported significant antidepressant-
      and anxiolytic-like effects of two dual 5-HT1A and 5-HT7 receptor antagonists in
      various behavioral tests in rodents. As a continuation of our previous
      experiments, in this study we aimed to investigate whether chronic administration
      of 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine
      hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2
      methoxyphenyl)piperazine hydrochloride (HBK-15) caused antidepressant-like
      effects and elevated serotonin levels in the murine hippocampus. We also
      evaluated cholinolytic properties and the influence of acute administration of
      both compounds on cognitive function in mice. To assess antidepressant-like
      properties and the influence on learning and memory we used forced swim test and
      step-through passive avoidance task in mice, respectively. Both compounds showed
      antidepressant-like properties and significantly elevated serotonin levels in the
      hippocampus after chronic treatment (HBK-14 - 2.5 mg/kg; HBK-15 - 0.625 and 1.25
      mg/kg). HBK-15 administered chronically antidepressant-like activity at lower
      dose (0.625 mg/kg) than the dose active after acute treatment (1.25 mg/kg). None
      of the compounds affected locomotor activity of mice. HBK-15 possessed very weak
      cholinolytic properties, whereas HBK-14 did not show any effect on muscarinic
      receptors. Only HBK-15 (0.625 mg/kg) presented memory-enhancing properties and
      ameliorated cognitive impairments caused by scopolamine (1 mg/kg). Our results
      indicate that 5-HT1A and 5-HT7 antagonists might have potential in the treatment
      of depression and possess positive influence on cognitive function.

PMID- 27888377
TI  - Correlation between status of epidermal growth factor receptor mutation and
      distant metastases of lung adenocarcinoma upon initial diagnosis based on 1063
      patients in China.
AB  - The study aimed to explore the correlations between status of epidermal growth
      factor receptor (EGFR) mutations and distant metastases. A total of 1063 patients
      with lung adenocarcinoma indentified with status of EGFR mutations from August
      2010 to May 2015 at Shanxi Cancer Hospital were enrolled. 456 patients were
      confirmed with EGFR mutations. The associations among EGFR mutations, clinical
      factors, and distant metastases at initial diagnosis were evaluated. Patients
      harboring EGFR mutation were more likely to be female (P < 0.001), with no
      smoking history (P < 0.001), brain metastases (P = 0.029), and higher ECOG
      performance scores (P = 0.025). The correlation between EGFR mutation status and
      distant metastases showed statistical significance both in univariate (P = 0.022)
      and in multivariate analysis (OR 1.573, 95 % CI 1.202-2.059, P = 0.001)
      especially in brain metastases (OR 1.675, 95 % CI 1.132-2.479, P = 0.010) and
      lung metastases (OR 1.571, 59 % CI 1.101-2.243 P = 0.013). Furthermore, the 19del
      mutations showed associations with brain metastases (OR 1.586, 95 % CI 1.028
      2.447, P = 0.037), and lung metastases (OR 1.587, 95 % CI 1.065-2.346, P =
      0.023). The exon 21 point mutations showed statistically significant differences
      in liver metastases (OR 1.987, 95 % CI 1.094-3.067, P = 0.024). In conclusion,
      the EGFR mutations in lung adenocarcinoma patients were independently correlated
      with distant metastases. Subgroup analyses showed that patients harboring 19del
      mutations presented different distant metastases compared with those harboring 21
      point mutaions.

PMID- 27888380
TI  - Kinetin improves motility, viability and antioxidative parameters of ram semen
      during storage at refrigerator temperature.
AB  - The present experiment was conducted to evaluate the effect of kinetin on ram
      semen quality during cold storage. Ejaculates were collected using an artificial
      vagina from five Qezel rams. Ejaculates which met the criteria (volume of 0.75-2
      ml; minimum spermatozoa concentration of 2.5 * 109 spermatozoa/ml and forward
      progressive motility of 80%), were pooled, diluted with extender without kinetin
      (control) or enriched with 25 (K 25), 50 (K 50), 100 (K 100) and 200 (K 200) MUM
      kinetin at a final concentration of 500 * 106 spermatozoa per mL. Spermatozoa
      motion characteristics were evaluated by computer-assisted sperm analysis. In
      addition, percent of viability (spermatozoa showing no color was considered to be
      alive) and spermatozoa with intact plasma membrane (spermatozoa with
      curled/swollen tail was considered healthy) were determined. Moreover, amounts of
      malondialdehyde (MDA), total antioxidant activity (AOA), nitric oxide (NO) and
      superoxide dismutase (SOD) activity were determined in the seminal plasma and
      spermatozoa at 0, 24, 48 and 72 h of storage. Higher percent of total and forward
      progressive motility was observed in K 25, K 50 and K 100 groups compared to
      control group at 72 h of storage (P < 0.001). Moreover, K 25 (78.61 +/- 1.11%), K
      50 (82.46 +/- 1.08%) and K 100 (82.96 +/- 1.49%) groups showed higher percentage
      of viability compared to control (72.38 +/- 1.49%) at 72 h of storage (P < 0.05).
      Semen enrichment with kinetin resulted in the higher percent of intact plasma
      membrane of spermatozoa at 48 and 72 h (P < 0.001). Amounts of MDA were lower and
      amounts of AOA were higher in K 50 and K 100 groups compared to control at 48 and
      72 h (P < 0.05). There were no significant differences in NO levels and SOD
      activities of seminal plasma and spermatozoa among groups during the experiment.
      The present experiment revealed that kinetin at proper concentration could
      enhances spermatozoa kinematics, viability, spermatozoa plasma membrane
      functionality and amounts of AOA and reduces the level of lipid peroxidation
      during chilled storage of ram semen.

PMID- 27888381
TI  - Listening to Quackery: Reading John Wesley's Primitive Physic in an Age of Health
      Care Reform.
AB  - This article uses a reading of John Wesley's Primitive Physic, or An Easy and
      Natural Method of Curing Most Diseases (1747) to resist the common rejection
      often as "quackery"-of Wesley's treatments for common maladies. We engage Wesley
      not because he was right but because his approach offers useful moments of pause
      in light of contemporary medical epistemology. Wesley's recommendations were
      primarily oriented towards the categories of personal responsibility and
      capability, but he also sought to empower individuals-especially the poor-with
      the knowledge to safely and affordably treat maladies of their own. We leverage
      Primitive Physic to rethink contemporary medical knowledge production, especially
      as sanctioned by randomized clinical trials and legitimate views of experience
      and contemporary institutions such as the AMA. Ultimately, we suggest that the
      medical humanities has a key role to play in mining the discarded and dismissed
      for what they can tell scholars about medical knowledge.

PMID- 27888376
TI  - Laser flare-cell photometer: principle and significance in clinical and basic
      ophthalmology.
AB  - A slit-lamp examination is an indispensable and essential clinical evaluation
      method in ophthalmology, but, it is qualitative subjective. To complement its
      weaknesses in making a quantitative evaluation of flare intensity and number of
      cells in the aqueous humor in the eye, we invented the laser flare-cell
      photometer in 1988. The instrument enables a non-invasive quantitative evaluation
      of flare intensity and number of cells in the aqueous with good accuracy and
      repeatability as well as maneuverability equal to slit-lamp microscopy. The
      instrument can elucidate the pathophysiology in the blood-aqueous barrier (BAB)
      function in a variety of ocular disorders. The accuracy of the instrument makes
      it possible to investigate not only the pathophysiology of intraocular disorders
      but also the effects of various drugs and surgical procedures in BAB. The
      instrument does not only lighten the burden on patients in clinical examinations
      and study but it also helps minimize the sacrifice of experimental animals and
      improves the reliability of the results by minimizing inter-individual variations
      through its good repeatability. Here I shall relate how the instrument has been
      applied to clinical and basic studies in ophthalmology and what novel knowledge
      its application contributed to pathophysiology in ophthalmology.

PMID- 27888379
TI  - Medical Co-morbidities Among Patients with Severe Mental Illnesses in a Community
      Health Facility in Nigeria.
AB  - To examine prevalence of medical comorbidity (MCM) in schizophrenia (n = 1310)
      and in bipolar disorder (n = 1307) and the association of high burden of MCM (>=3
      MCM) with duration of untreated illness, number of episodes, functioning, poly
      medication and lifetime hospitalization for the mental disorder. Participants
      were recruited from a private psychiatric facility in Ibadan, Nigeria between
      2004 and 2013 and enquiry made about the lifetime occurrence of 20 common chronic
      diseases including common tropical diseases. Psychiatric diagnosis was made using
      the Structured Clinical Interview for DSM IV Axis I disorder (SCID). Except for
      nutritional anemia, dermatitis and intestinal Helminthiasis, patients with
      schizophrenia were not at higher odds of reporting MCM than those with bipolar
      disorder. DUI >=2 years, episodes of illness >=3, being on multiple neuroleptics
      and history of previous hospitalization were significantly associated with high
      burden of MCM in schizophrenia and episodes of illness >=3, reduced functioning
      and history of previous hospitalization with bipolar disorder. Schizophrenia and
      bipolar disorder are associated with high rates of medical comorbidity. Treatment
      of this medical comorbidity is essential in order to improve the outcomes for
      patients with bipolar disorder and schizophrenia.

PMID- 27888378
TI  - Interactive Effect of Immigration-Related Factors with Legal and Discrimination
      Acculturative Stress in Predicting Depression Among Asian American Immigrants.
AB  - This study examined the impact of discrimination and legal acculturative stress
      on Major Depression Episode lifetime among Asian American immigrants. It further
      examined the role of immigration related-factors (age at immigration, reason for
      immigration, and years spent in the U.S.) on the relationship of acculturative
      stress and Major Depression Episode lifetime. The National Latino and Asian
      American Study 2002-2003 dataset was used. The study findings were: (1) high
      discrimination and legal acculturative stress were associated with Major
      Depression Episode lifetime; (2) age at immigration buffered the relationship of
      discrimination acculturative stress and Major Depression Episode lifetime as well
      as the relationship of legal acculturative stress and Major Depression Episode
      lifetime; and (3) years spent in the U.S. buffered the relationship of
      discrimination acculturative stress and Major Depression Episode lifetime only.
      These findings highlight the complex relationship of factors that impact the
      mental health of the Asian American immigrants.

PMID- 27888382
TI  - "Say Your Favorite Poet in the World is Lying There": Eileen Myles, James
      Schuyler, and the Queer Intimacies of Care.
AB  - This article closely reads "Chelsea Girls," an autobiographical short story by
      Eileen Myles that depicts her experience caring for the diabetic, bipolar poet
      James Schuyler when she was a young writer getting started in East Village in the
      late 1970s. Their dependency relationship is a form of queer kinship, an early
      version of the caring relations between lesbians and gay men that HIV/AIDS would
      demand over the next two decades as chosen families emerged to nurture gay men
      and lesbians rejected by their families of origin. The representation of queer
      kinship offers an alternative to more traditional portrayals of care in
      literature that focus on the heteronormative family, a site of care that feminist
      dependency theory also paradoxically privileges. This article synthesizes
      insights from queer theory and critical disability studies in order to expand our
      understanding of the roles participants in care can play, the ways they can feel,
      and the outcomes they can achieve. Myles and Schuyler's dependency relationship
      was sustaining for both of them and also critical for her development as a
      pioneering lesbian poet in an art world still dominated by men.

PMID- 27888383
TI  - Relationships between blood mercury levels, reproduction, and return rate in a
      small seabird.
AB  - Mercury (Hg) is a ubiquitous heavy metal that occurs naturally in the
      environment, but its levels have been supplemented for decades by a variety of
      human activities. Mercury can have serious deleterious effects on a variety of
      organisms, with top predators being particularly susceptible because
      methylmercury bioaccumulates and biomagnifies in food webs. Among birds, seabirds
      can have especially high levels of Hg contamination and Leach's storm-petrels
      (Oceanodroma leucorhoa), in particular, have amongst the highest known levels.
      Several populations of Leach's storm-petrels have declined recently in the
      Northwest Atlantic. The causes of these declines remain uncertain, but the toxic
      effects of Hg could be a potential factor in this decline. Here, we tested for
      relationships between adult blood total Hg (THg) concentration and several
      offspring development parameters, and adult return rate of Leach's storm-petrels
      breeding on Bon Portage Island (43 degrees  28' N, 65 degrees  44' W), Nova
      Scotia, Canada, between 2011 and 2015 (blood samples n = 20, 36, 6, 15, and 13
      for each year, respectively). Overall, THg levels were elevated (0.78 +/- 0.43
      MUg/g wet wt.) compared to other species of seabirds in this region, and varied
      significantly among years. However, we found no associations between THg levels
      and reproductive parameters or adult return rate. Our results indicate that
      levels of mercury observed in Leach's storm-petrel blood, although elevated,
      appear not to adversely affect their offspring development or adult return rate
      on Bon Portage Island.

PMID- 27888384
TI  - Exploiting histone deacetylases for cancer therapy: from hematological
      malignancies to solid tumors.

PMID- 27888385
TI  - Targeting SPOP with small molecules provides a novel strategy for kidney cancer
      therapy.

PMID- 27888387
TI  - Incubation experiment demonstrates effects of carbon and nitrogen on microbial
      phosphate-solubilizing function.

PMID- 27888386
TI  - Innate recognition of microbial-derived signals in immunity and inflammation.
AB  - Microbes generate a vast array of different types of conserved structural
      components called pathogen-associated molecular patterns (PAMPs), which can be
      recognized by cells of the innate immune system. This recognition of "nonself"
      signatures occurs through host pattern recognition receptors (PRRs), suggesting
      that microbial-derived signals are good targets for innate immunity to
      discriminate between self- and nonself. Such PAMP-PRR interactions trigger
      multiple but distinct downstream signaling cascades, subsequently leading to
      production of proinflammatory cytokines and interferons that tailor immune
      responses to particular microbes. Aberrant PRR signals have been associated with
      various inflammatory diseases and fine regulation of PRR signaling is essential
      for avoiding excessive inflammatory immune responses and maintaining immune
      homeostasis. In this review we summarize the ligands and signal transduction
      pathways of PRRs and highlight recent progress of the mechanisms involved in
      microbe-specific innate immune recognition during immune responses and
      inflammation, which may provide new targets for therapeutic intervention to the
      inflammatory disorders.

PMID- 27888388
TI  - Cardiac BIN1 (cBIN1) is a regulator of cardiac contractile function and an
      emerging biomarker of heart muscle health.
AB  - In recent decades, a cardiomyocyte membrane scaffolding protein bridging
      integrator 1 (BIN1) has emerged as a critical multifunctional regulator of
      transverse-tubule (t-tubule) function and calcium signaling in cardiomyocytes.
      Encoded by a single gene with 20 exons that are alternatively spliced, more than
      ten BIN1 protein isoforms are expressed with tissue and disease specificity. The
      recently discovered cardiac alternatively spliced isoform BIN1 (cBIN1 or
      BIN1+13+17)plays a crucial role in organizing membrane microfolds within cardiac
      t-tubules. These cBIN1-induced microfolds form functional dyad microdomains by
      trafficking L-type calcium channels (LTCC) to t-tubule membrane and recruiting
      ryanodine receptors (RyR) to junctional sarcoplasmic reticulum membrane. When
      cBIN1 is transcriptionally reduced as occurs in heart failure, cBIN1-microfolds
      are disrupted and fail to form LTCC and RyR couplons. As a result, impaired dyad
      formation limits excitation-contraction coupling thus cardiac contractility, and
      accumulation of orphaned leaky RyRs outside of dyads increases ventricular
      arrhythmias. Reduced myocardial BIN1 in heart failure is also detectable at the
      blood level, and plasma BIN1 level predicts heart failure progression and future
      arrhythmias in cardiomyopathy patients. Here we will review the recent progress
      in BIN1-related cardiomyocyte biology studies and discuss the diagnostic and
      predictive values of cBIN1 in future clinical use.

PMID- 27888389
TI  - Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder
      Carcinogenesis.
AB  - PURPOSE: Gallstone is a high-risk factor for gallbladder pre-malignancy or
      malignancy (GB PM-M) but which substances of gallstones definitely assist to turn
      out in to GB PM-M, remains unclear. This study aimed to find out the presence of
      carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of
      gallbladder pre-malignancy and malignancy. METHODS: Presence of elements in
      gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with
      scanning electron microscopy (SEM) and then level of carcinogenic heavy metals
      was estimated in gallstones using atomic absorption spectroscopy (AAS). The
      experiment was carried out in gallstone samples of 46 patients with gallbladder
      pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched
      patients with chronic cholecystitis (C-C group). Gallstones were also classified
      in to three types such as cholesterol stone, mixed stone, and black pigment
      stone. RESULTS: EDS analysis detected presence of mercury, lead, and cobalt
      elements in all types of gallstones of both PM-M and C-C groups. AAS analysis
      revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001),
      cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C
      groups. The presence of these heavy metals also varied among stone types of both
      groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones.
      CONCLUSIONS: Presence of significantly higher amount of mercury, lead, cobalt,
      and cadmium in gallstones may play a pivotal role as risk factors in the
      development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of
      these metals in the gallstones which is the first observation, may act as crucial
      doses of carcinogens.

PMID- 27888390
TI  - What Do We Need to Know About Colonic Polypoid Ganglioneuroma? A Case Report and
      A Comprehensive Review.

PMID- 27888391
TI  - Small Bowel Adenocarcinoma in Celiac Disease: a Case Report.

PMID- 27888393
TI  - Erratum to: Associations between adult attachment and: oral health-related
      quality of life, oral health behaviour, and self-rated oral health.

PMID- 27888392
TI  - Factors associated with the quality of life of mothers of preterm infants with
      very low birth weight: a 3-year follow-up study.
AB  - AIM: To analyze possible factors associated with the quality of life (QoL) of
      mothers of preterm infants with very low birth weight (VLBW) during the first 3
      years after delivery. METHODS: The World Health Organization Quality of Life
      (WHOQOL)-bref scores were compared and correlated with maternal and infant
      related sociodemographic and clinical variables at maternal discharge (T0) and at
      6 (T1), 12 (T2), 24 (T3), and 36 (T4) months after delivery. Multiple linear
      regression models were fitted to investigate the effect of these variables on the
      mothers' QoL. RESULTS: The WHOQOL-BREF physical domain scores were higher at T1
      and T2 compared to T0 (p = 0.013). Maternal variables that contributed to
      maternal QoL scores (p < 0.05) were stable marital union (b = 13.60; T0), family
      income (b = -12.75; T3), Evangelical religion (b = 8.11; T4), and beck depression
      inventory (BDI) score (-1.42 <= b <= -0.36; T0, T1, T2, T3, and T4). Infants'
      variables that most affected maternal QoL (p < 0.05) were posthemorrhagic
      hydrocephalus (PHH) (-18.84 <= b <= -10.05; T1, T2, and T4), bronchopulmonary
      dysplasia (BPD) (b = -7.41; T2), female gender (b = 8.09; T2), and SNAPPE
      severity score (b = -0.23; T3). CONCLUSION: Mothers of preterm infants with VLBW
      exhibited transient improvements in physical well-being during the first year
      after delivery. The presence of depressive symptoms in mothers and the diagnosis
      of PHH or BPD were negatively associated with QoL. Social, religious, and
      economic aspects were also important factors for the QoL of mothers of preterm
      infants with VLBW.

PMID- 27888394
TI  - Comparative evaluation of hormonal protocol on the performance of crossbred
      cattle.
AB  - A total of 60 animals (38 cows, 22 heifers) were selected and were divided into
      three groups of 20 animals each (containing both anoestrus and repeat breeder) in
      which treatment was performed for 60 days. Group I: control (farmer practice), T1
      group: group I + hormone (double synch), and T2 group: group I + hormone (Estra
      double synch). The growth performances were measured in terms of body weight and
      average daily gain (ADG). Blood collection was done at the start and end of the
      experiment for assessment of blood biochemical, hematological, and reproductive
      status of the animals. Results revealed significant improvement in growth and
      reproductive performances in treatment group as compared to control group. Higher
      percentage of conception was achieved in group III (60%) followed by group II
      (55%). The least percentage was in group I (15%), i.e., in control group. So it
      was found that the effect of treating the reproductive-disordered animals with
      Estra double synch gave comparatively better result than double synch hormonal
      application.

PMID- 27888395
TI  - Utility of FVC/DLCO ratio to stratify the risk of mortality in unselected
      subjects with pulmonary hypertension.
AB  - In patients with systemic sclerosis, a ratio between forced vital capacity (FVC)
      and diffusing capacity of carbon monoxide (DLCO, FCV%/DLCO%) >1.5 might be a
      predictor of pulmonary hypertension (PH). The aim of this study is, therefore, to
      evaluate whether this index can be used in patients with PH, regardless of
      etiology. 83 consecutive outpatients with suspected PH at non-invasive work-up
      underwent spirometry and DLCO test before right heart catheterization (RHC);
      FVC%/DLCO% ratio was then calculated and compared with mean pulmonary-artery
      pressure (mPAP) and mortality at 5-year follow-up. Significant correlations
      between FVC%/DLCO% and PAsP and mPAP levels were found (p < 0.05). After ROC
      curve analysis and definition of best cut-off values for PAsP and FVC%/DLCO%,
      increased mPAP values at RHC were observed comparing subjects with both PAsP and
      FVC%/DLCO% values below cut off values (-/-), either PAsP or FVC%/DLCO% above cut
      off values (+/-), or both above (+/+) (p < 0.05). Poorer survival rates are
      observed at follow-up with higher FVC%/DLCO% values (0% for <1, 17.4% for 1-3,
      33.3% for >3, p < 0.05), when comparing subjects with either increased PAsP and
      FVC%/DLCO% values or both with those with lower (log-rank p < 0.05). Even in
      subjects with mPAP at RHC >25 mmHg, increased FVC%/DLCO% values predicted a worse
      outcome (p < 0.05). FVC%/DLCO% values are related to mPAP in subjects with
      suspected PH, and may further stratify the risk of mortality in addition to PAP.

PMID- 27888396
TI  - Effects of Administered Ethanol and Methamphetamine on Glial Glutamate
      Transporters in Rat Striatum and Hippocampus.
AB  - Exposure to ethanol (EtOH) or methamphetamine (MA) can lead to increase in
      extracellular glutamate concentration in the brain. Although studies from ours
      showed the effects of EtOH exposure on key glial glutamate transporters, little
      is known about the effects of sequential exposure to EtOH and MA or MA alone on
      certain glial glutamate transporters. In this study, we investigated the effects
      of sequential exposure to EtOH and MA on the expression of the major glutamate
      transporters, glutamate transporter 1 (GLT-1), as well as cystine/glutamate
      antiporter (xCT) and glutamate aspartate transporter (GLAST) in striatum and
      hippocampus. We also tested the effects of ceftriaxone (CEF), known to upregulate
      GLT-1, in animals administered EtOH and MA. Wistar rats were orally gavaged with
      EtOH (6 g/kg) or water for 7 days. On the following day (day 8), the rats
      received four intraperitoneal (i.p.) injections of MA (10 mg/kg) or saline
      (vehicle) occurring every 2 h. The rats were then treated with CEF (200
      mg/kg/day, i.p.) or saline on days 8, 9, and 10. EtOH or MA exposure caused a
      significant downregulation of GLT-1 expression as compared to control groups in
      striatum and hippocampus. Furthermore, sequential exposure of EtOH and MA caused
      a significant downregulation of GLT-1 expression as compared to either drug
      administered alone in both brain regions. Importantly, GLT-1 expression was
      restored following CEF treatment. There were no significant differences on xCT
      and GLAST expression in striatum and hippocampus between all groups. These
      findings demonstrated that sequential exposure to EtOH and MA has additive effect
      in downregulation of GLT-1 and this effect can be attenuated by CEF treatment.

PMID- 27888397
TI  - Synaptosome-Associated Protein 25 (SNAP25) Gene Association Analysis Revealed
      Risk Variants for ASD, in Iranian Population.
AB  - Autism spectrum disorder (ASD) is a common, complex neurological condition,
      affecting approximately 1% of people worldwide. Monogenic neurodevelopmental
      disorders which showed autistic behavior patterns have suggested synaptic
      dysfunction, as a key mechanism in the pathophysiology of ASD. Subsequently,
      genes involved in synaptic signaling have been investigated with a priority for
      candidate gene studies. A synaptosomal-associated protein 25 (SNAP25) gene plays
      a crucial role in the central nervous system, contributing to exocytosis by
      targeting and fusion of vesicles to the cell membrane. Studies have shown a
      correlation between aberrant expression of the SNAP25 and a variety of brain
      diseases. Single nucleotide polymorphisms (SNPs) in this gene are associated with
      several psychiatric diseases, such as bipolar, schizophrenia, and attention
      deficit/hyperactivity disorder. The aim of the present study was to investigate
      whether polymorphisms (rs3746544 and rs1051312) in the regulatory 3'-untranslated
      region (3'UTR) of the SNAP25 gene have an association with ASD in unrelated
      Iranian case (N = 524)-control (N = 472) samples. We observed robust association
      of the rs3746544 SNP and ASD patients, in both allele and haplotype-based
      analyses. Our results supported the previous observations and indicated a
      possible role for SNAP25 polymorphisms as susceptibility genetic factors involved
      in developing ASD.

PMID- 27888398
TI  - The Value of the Electrocardiogram for Evaluating Prognosis in Patients with
      Idiopathic Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Association between electrocardiography (ECG) features and right
      ventricular anatomy and physiology has been established. This study is aimed to
      identify the value of 12-lead ECG in evaluating prognosis of patients with
      idiopathic pulmonary arterial hypertension (IPAH). METHOD: 194 patients with
      newly diagnosed IPAH were included in this study. Correlations between
      electrocardiography variables and hemodynamics were assessed. Univariate and
      multivariable cox regression analysis were performed to identify ECG variables
      for predicting all-cause mortality in IPAH. RESULTS: Partial correlation analysis
      showed that P wave amplitude in lead II correlated with the mean pulmonary
      arterial pressure (mPAP, r = 0.349, p <= 0.001) and cardiac index (CI, r = 
      0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p <=
      0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI
      (r = -0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R
      wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors
      of all-cause mortality. Kaplan-Meier survival curves showed patients with a p >=
      0.25 mv in lead II, and R >= 0.4 mv in lead aVR had lower 3-year survival (55 vs.
      91%, p < 0.001). CONCLUSION: Specific lead-12 ECG features could reflect right
      ventricular overload hemodynamics, and are useful to evaluate prognosis of
      patients with IPAH.

PMID- 27888399
TI  - Effectiveness and Safety of Bariatric Surgery in the Public Healthcare System in
      Brazil: Real-World Evidence from a High-Volume Obesity Surgery Center.
AB  - BACKGROUND: This study aimed to evaluate the waiting time, safety, and
      effectiveness of bariatric surgery based on real-world data. METHODS: This is a
      noninterventional, noncomparative, and retrospective study with 300 morbidly
      obese patients who had undergone open Roux-en-Y surgery. RESULTS: The procedure
      was found to be very safe, with low rates of overall complications (10.7%).
      Approximately 48.4% of the patients had reached a BMI <30 mg/kg2 at 12 months
      after surgery, while 6% were still classified as morbidly obese (BMI >40 mg/kg2).
      Comorbidity resolution was over 90% for all conditions, except for cardiovascular
      disease, which showed a 40% resolution. The mean number of drugs taken also
      decreased at 12 months after surgery. CONCLUSIONS: Bariatric surgery was found to
      be effective in weight reduction and in the resolution of comorbidities.

PMID- 27888400
TI  - Repression of CDKN2C caused by PML/RARalpha binding promotes the proliferation
      and differentiation block in acute promyelocytic leukemia.
AB  - Inappropriate cell proliferation during oncogenesis is often accompanied by
      inactivation of components involved in the cell cycle machinery. Here, we report
      that cyclin-dependent kinase inhibitor 2C (CDKN2C) as a member of the cyclin
      dependent kinase inhibitors is a target of the PML/RARalpha oncofusion protein in
      leukemogenesis of acute promyelocytic leukemia (APL).We found that CDKN2C was
      markedly downregulated in APL blasts compared with normal promyelocytes.
      Chromatin immunoprecipitation combined with quantitative polymerase chain
      reaction demonstrated that PML/RARalpha directly bound to the CDKN2C promoter in
      the APL patient-derived cell line NB4. Luciferase assays indicated that
      PML/RARalpha inhibited the CDKN2C promoter activity in a dose-dependent manner.
      Furthermore, all-trans retinoic acid treatment induced CDKN2C expression by
      releasing the PML/RARalpha binding on chromatin in NB4 cells. Functional studies
      showed that ectopic expression of CDKN2C induced a cell cycle arrest at the G0/G1
      phase and a partial differentiation in NB4 cells. Finally, the transcriptional
      regulation of CDKN2C was validated in primary APL patient samples. Collectively,
      this study highlights the importance of CDKN2C inactivation in the abnormal cell
      cycle progression and differentiation block of APL cells and may provide new
      insights into the study of pathogenesis and targeted therapy of APL.

PMID- 27888401
TI  - The impact of chronic hepatitis C infection on cholesterol metabolism in PBMCs is
      associated with microRNA-146a expression.
AB  - Chronic hepatitis C (CHC) infection is known to induce important changes in host
      cholesterol metabolism. MicroRNAs (miRNAs) regulate the expression of many genes
      and, in consequence, control various processes, including human metabolism and
      response to viral infection. Recently, the alteration of the immune-associated
      miR-146a, which is abundantly present in peripheral blood mononuclear cells
      (PBMCs), was found in some viral infections. The study aimed to analyse the
      influence of hepatitis C virus (HCV) infection on miR-146a expression in PBMCs in
      vivo and in vitro, as well as to assess the possible impact of miR-146a
      alteration on the intracellular cholesterol level in PBMCs. Blood samples
      collected from 42 healthy donors and 72 CHC patients were the source of
      materials. HCV RNA, intracellular cholesterol level and miR-146a expression were
      determined in PBMCs, as well as HCV genotype and interferon (IFN)alpha
      concentration in sera. The influence of miR-146a inhibition on cholesterol
      expression in PBMCs was analysed in vitro after transient cell transfections with
      mirVanaTM anti-miR-146a Inhibitor. Our data demonstrated an alteration of miR
      146a and intracellular cholesterol expression in PBMCs and of IFNalpha
      concentration in sera of genotype 1, HCV-infected patients compared to the
      healthy donors. Also, in cultured PBMCs, miR-146a expression and intracellular
      cholesterol level were significantly decreased in CHC patients compared to the
      healthy donors. In vitro blockage of miR-146a expression in PBMCs of CHC patients
      greatly impaired intracellular cholesterol expression. In these conditions, miR
      146a expression was positively correlated with the intracellular cholesterol
      level. These results suggest that genotype 1 HCV infection may alter miR-146a
      expression in PBMCs and, consequently, contribute to the observed dysregulation
      of cholesterol synthesis.

PMID- 27888402
TI  - Infectious encephalitis: utility of a rational approach to aetiological diagnosis
      in daily clinical practice.
AB  - In this study we attempt to assess the utility of a simplified step-wise
      diagnostic algorithm to determinate the aetiology of encephalitis in daily
      clinical practice and to describe the main causes in our setting. This was a
      prospective cohort study of all consecutive cases of encephalitis in adult
      patients diagnosed between January 2010 and March 2015 at the University Hospital
      Vall d'Hebron in Barcelona, Spain. The aetiological study was carried out
      following the proposed step-wise algorithm. The proportion of aetiological
      diagnoses achieved in each step was analysed. Data from 97 patients with
      encephalitis were assessed. Following a simplified step-wise algorithm, a
      definite diagnosis was made in the first step in 53 patients (55 %) and in 12
      additional cases (12 %) in the second step. Overall, a definite or probable
      aetiological diagnosis was achieved in 78 % of the cases. Herpes virus, L.
      monocytogenes and M. tuberculosis were the leading causative agents demonstrated,
      whereas less frequent aetiologies were observed, mainly in immunosuppressed
      patients. The overall related mortality was 13.4 %. According to our experience,
      the leading and treatable causes of encephalitis can be identified in a first
      diagnostic step with limited microbiological studies. L. monocytogenes treatment
      should be considered on arrival in some patients. Additional diagnostic effort
      should be made in immunosuppressed patients.

PMID- 27888403
TI  - The predictor of mortality outcome in adult patients with Ebola virus disease
      during the 2014-2015 outbreak in Guinea.
AB  - The purpose of this study was to examine the association of any demographic and
      clinical factors with mortality outcome among adult patients with Ebola virus
      disease (EVD) in Guinea. This retrospective observational study analyzed medical
      records of laboratory confirmed EVD adult patients during the 2014-2015 EVD
      outbreak in Guinea. The associations between any demographic or clinical
      variables and mortality outcome of EVD were assessed using univariate and
      multivariate logistic regression analyses. Of 2,310 EVD adult patients included
      for analysis, the overall case fatality rate was 68.1%. Univariate analyses
      identified factors possibly associated with mortality outcome, including patient
      age (p < 0.001), history of visiting or close contact with a suspected or
      confirmed EVD patient (p = 0.035), and seven clinical symptoms on admission,
      i.e., fever (p = 0.003), hiccups (p < 0.001), vomiting (p = 0.003), diarrhea (p <
      0.001), cough (p = 0.001), sore throat (p = 0.016), and unexplained bleeding (p =
      0.021). The multivariate analysis showed that patient age was independently
      associated with mortality outcome of EVD (OR = 1.06; 95%CI = 1.03-1.09; p <
      0.001), while none the of clinical symptoms on admission were significantly
      associated with the mortality outcome. Our analysis indicates that older age was
      the only independent factor associated with death among EVD adult patients in
      Guinea. This suggests that older EVD patients should receive intensive medical
      care and be carefully monitored.

PMID- 27888404
TI  - Ab initio and density functional theory (DFT) studies on triflic acid with water
      and protonated water clusters.
AB  - The structure, stability and infrared spectral signatures of triflic acid (TA)
      with water clusters (Wn) and protonated water clusters (TAH+Wn, n = 1 - 6) were
      computed using DFT and MP2 methods. Our calculations show that a minimum of three
      water molecules are necessary to stabilize the dissociated zwitterionic form of
      TA. It can be seen from the results that there is no significant movement of
      protons in smaller (n = 1 and 2) and linear (n = 1 - 6) types of water clusters.
      Further, the geometries of TAWn clusters first form a neutral pair (NP) to
      contact ion pair (CIP), then form a solvent separated ion pair (SSIP) in a water
      hexamer. These findings reveal that proton transfer may take place through NP to
      CIP and then CIP to SSIP. The calculated binding energies (BEs) of ion pair
      clusters is always higher than that of NP clusters (i.e., more stable than the
      NP). Existing excess proton linear chain clusters transfer a proton to adjacent
      water molecules via a Grotthuss mechanism, whereas the same isomers in the
      branched motifs do not conduct protons. Examination of geometrical parameters and
      infrared frequencies reveals hydronium ion (H3O+ also called Eigen cation)
      formation in both TAWn and protonated TAWn clusters. The stability of Eigen water
      clusters is three times higher than that of other non-Eigen water clusters. Our
      study shows clearly that formation of ion pairs in TAWn and TAH+Wn clusters
      greatly favors proton transfer to neighboring water molecules and also enhances
      the stability of these complexes.

PMID- 27888406
TI  - Rotovibrational states of the water molecule on the sun.
AB  - The infrared spectrum of water observed in sunspots is complex and dense, with
      bands separated by approximately 0.01 cm-1. For top asymmetrical molecules, there
      is no theoretical approach that allows for the calculation of rotovibrational
      energy with such precision. Experimentally derived rotovibracional energy levels
      of water at high temperatures combined with variational calculations have been
      used for the band assignments. These energy levels are employed to refine the
      analysis of a small portion of the infrared absorption spectrum. Such procedure
      has allowed for the identification of additional 55 bands to the 70 already
      identified as rotovibrational transitions of the water molecule. Our new
      assignments, which include pure and cross transitions, offer additional evidence
      of the existence of water on the sun, but above all they illustrate the
      complexity of the solar spectrum that involves states with higher levels of
      rotational excitation. Given the conditions on the sun, more molecules of water
      would occur in excited electronic states, which include apolar and paramagnetic
      states, generating intense bands in the spectrum. Since there is an analytical
      solution for the rotovibrational transitions of linear molecules, we were able to
      identify 16 bands relative to the excited electronic states 1B2 and 3A1 in the
      sunspot spectrum. Density functional B3LYP/AUG-cc-pVTZ calculations of the
      electric and magnetic dipole are employed to discuss some consequences of the
      presence of excited states of water in the dynamics of sunspots and solar
      magnetic field.

PMID- 27888405
TI  - Characterization of B-H agostic compounds involved in the dehydrogenation of
      amine-boranes by group 4 metallocenes.
AB  - For over a decade, amine-borane has been considered as a potential chemical
      hydrogen vector in the context of a search for cleaner energy sources. When
      catalyzed by organometallic complexes, the reaction mechanisms currently
      considered involve the formation of beta-BH agostic intermediates. A thorough
      understanding of these intermediates may constitute a crucial step toward the
      identification of ideal catalysts. Topological approaches such as QTAIM and ELF
      revealed to be particularly suitable for the description of beta-agostic
      interactions. When studying model catalysts, accurate theoretical calculations
      may be carried out. However, for a comparison with experimental data,
      calculations should also be carried out on large organo-metallic species, often
      including transition metals belonging to the second or the third row. In such a
      case, DFT methods are particularly attractive. Unfortunately, triple-zeta all
      electrons basis sets are not easily available for heavy transition metal
      elements. Thus, a subtle balance should be reached between the affordable level
      of calculations and the required accuracy of the electronic description of the
      systems. Herein we propose the use of B3LYP functional in combination with the
      LanL2DZ pseudopotential for the metal atom and 6-311++G(2d,2p) basis set for the
      other atoms, followed by a single point using the DKH2 relativistic Hamiltonian
      in combination with the B3LYP/DZP-DKH level, as a "minimum level of theory"
      leading to a consistent topological description of the interaction within the ELF
      and QTAIM framework, in the context of isolated (gas-phase) group 4 metallocene
      catalysts.

PMID- 27888407
TI  - Targeting the rhesus macaque TRIM5alpha gene to enhance the susceptibility of
      CD4+ T cells to HIV-1 infection.
AB  - The host range of human immunodeficiency virus type 1 (HIV-1) is extremely
      narrow, which has hampered the establishment of non-human primate models for HIV
      1 infection. The species-specific innate immune factor tripartite motif 5 alpha
      (TRIM5alpha) is a key molecule that confers potent resistance against HIV-1
      infection. In this study, we targeted the TRIM5alpha gene of rhesus macaques
      (rhTRIM5alpha) using the transcription activator-like effector nuclease (TALEN)
      to study the effect on HIV-1 infection. CD4+ T cells were separated from the
      peripheral blood of rhesus macaques by magnetic cell sorting, and the positive
      rate was greater than 99%. TALEN plasmids targeting rhTRIM5alpha were constructed
      and introduced into CD4+ T cells by electroporation, with a transfection
      efficiency of approximately 25%. The genome of the targeted cells was extracted,
      and the target efficiency was analyzed by T7E1 enzyme digestion. After sorting
      the positive transductants, the TALENs induced rhTRIM5alpha mutations at a rate
      of more than 40%. The ability of the HIV-1 virus to infect the targeted cells was
      demonstrated by ELISA. The results showed that targeting rhTRIM5alpha enhanced
      the susceptibility to HIV-1 infection. This finding will pave the way for further
      establishment of a new rhesus macaque model for HIV-1 studies.

PMID- 27888408
TI  - Extra-intestinal detection of canine kobuvirus in a puppy from Southern Brazil.
AB  - This study presents the pathological, immunohistochemical, and molecular findings
      associated with the extra-intestinal detection of canine kobuvirus (CaKV) in a 5
      month-old Chihuahua puppy, that had a clinical history of bloody-tinged feces.
      Principal pathological findings were interstitial pneumonia, necrotizing
      bronchitis, and parvovirus-induced enteritis. Molecular diagnostic methods
      identified CaKV within the cerebellum, cerebrum, lung, tonsil, and liver. CaKV
      and rotavirus were not identified within the feces and intestine.
      Immunohistochemistry (IHC) assays detected antigens of CDV and CAdV-1 in the
      lungs. These results confirmed the extra-intestinal detection of CaKV in this
      puppy and represent the first extra-intestinal detection of CaKV in a dog.

PMID- 27888409
TI  - Duplications in the 3' termini of three segments of Fusarium graminearum virus
      China 9.
AB  - The hypovirulence-inducing Fusarium graminearum virus China 9 (FgV-ch9) was
      described recently and is closely related to the Fusarium graminearum mycovirus-2
      (FgV2). Both viruses share common properties of viruses belonging to the family
      Chrysoviridae. Re-sequencing of FgV-ch9 revealed duplications of the 3' non
      coding regions of segments 2 and 3. Both duplications are arranged in a head-to
      tail array, are attached to the complete terminus, and do not affect the encoded
      gene. An internal duplication was found in segment 5. This duplication resulted
      in an increase in the size of the encoded protein. In silico analysis showed
      similar duplications in segments 2 and 3 of FgV2.

PMID- 27888410
TI  - Genome sequence, prevalence and quantification of the first iflavirus identified
      in a phytoplasma insect vector.
AB  - The leafhopper Euscelidius variegatus is a natural vector of chrysanthemum
      yellows phytoplasma (CY) and an efficient vector of flavescence doree phytoplasma
      (FD) under laboratory conditions. During a transcriptome sequencing (RNA-seq)
      project aimed at investigating the interactions between the insect and the two
      phytoplasmas, a 10,616-nucleotide-long contig with high sequence similarity to
      known picorna-like viruses was identified among the assembled insect transcripts.
      The discovery came totally unexpected, because insects from the laboratory colony
      did not show any evident symptom that could be related to the presence of a
      virus. The amino acid sequence, the shape and size of viral particles, and the
      results of phylogenetic analysis suggest that this virus, named Euscelidius
      variegatus virus 1 (EVV-1), can be considered a new member of a new species in
      the genus Iflavirus. EVV-1 was detected in all of the tested insects from the
      laboratory colony used for RNA-seq, both in phytoplasma-exposed and in non
      exposed insects, but the viral load measured in FD-exposed samples was
      significantly lower than that in non-exposed insects. This result suggests the
      possible existence of an intriguing cross-talk among insects, endogenous
      bacteria, and viruses. The identification of two other E. variegatus laboratory
      colonies that were free of EVV-1 could represent the key to addressing some basic
      virological issues, e.g., viral replication and transmission mechanisms, and
      offer the opportunity to use infectious clones to express heterologous genes in
      the leafhopper and manipulate the expression of endogenous genes by promoting
      virus-induced gene silencing.

PMID- 27888411
TI  - To screen or not to screen for vesicoureteral reflux in children with
      ureteropelvic junction obstruction: a systematic review.
AB  - : Ureteropelvic junction obstruction (UPJO) and vesicoureteral reflux (VUR) are
      the most common uropathies. The co-occurrence of both anomalies has led to the
      practice of screening for VUR in children with UPJO to prevent deterioration of
      kidney function due to renal scarring following urinary tract infections (UTIs).
      We determined the prevalence of VUR in children with UPJO for a critical
      assessment of VUR screening by voiding cystourethrography (VCUG). A systematic
      search strategy in MEDLINE, EMBASE, and CENTRAL was carried out for all articles
      that included VCUG, and renal scintigraphy or any other appropriate imaging
      technique for the diagnosis of UPJO. Twenty studies were eligible for inclusion.
      We found a pooled prevalence for VUR of 8.2 % (95 % CI = 3.6-12.7), about a
      threefold increase compared to the general pediatric population. VUR occurred
      bilateral or contralateral to the kidney with UPJO in 5.7 % (95 % CI = 3.0-8.5),
      equivalent to 75 % of all children with VUR. Considering the effect size of VUR
      treatment with antibiotics, about 207 and 278 children would need to undergo VCUG
      to prevent one febrile UTI and one case of renal scarring by 1-2 years,
      respectively. CONCLUSION: Against this background, screening for VUR needs to be
      scrutinized and restricted to selected risk groups. What is known: * Screening of
      patients with ureteropelvic junction obstruction (UPJO) for vesicoureteral reflux
      (VUR) is recommended based on a small number of repeatedly cited studies. * The
      lack of conclusive evidence results in different treatment strategies and leads
      to difficulties when communicating diagnoses and treatment options to parents.
      What is new: * A robust prevalence for VUR in children with UPJO based on all
      published evidence and the resulting number needed to screen are given for
      decision-making in daily clinical practice. * The results may be a precursor for
      implementation into guidelines.

PMID- 27888412
TI  - Diabetes screening in overweight and obese children and adolescents: choosing the
      right test.
AB  - : Type 2 diabetes can occur without any symptoms, and health problems associated
      with the disease are serious. Screening tests allowing an early diagnosis are
      desirable. However, optimal screening tests for diabetes in obese youth are
      discussed controversially. We performed an observational multicenter analysis
      including 4848 (2668 female) overweight and obese children aged 7 to 17 years
      without previously known diabetes. Using HbA1c and OGTT as diagnostic criteria,
      2.4% (n = 115, 55 female) could be classified as having diabetes. Within this
      group, 68.7% had HbA1c levels >=48 mmol/mol (>=6.5%). FPG >=126 mg/dl (>=7.0
      mmol/l) and/or 2-h glucose levels >=200 mg/dl (>=11.1 mmol/l) were found in
      46.1%. Out of the 115 cases fulfilling the OGTT and/or HbA1c criteria for
      diabetes, diabetes was confirmed in 43.5%. For FPG, the ROC analysis revealed an
      optimal threshold of 98 mg/dl (5.4 mmol/l) (sensitivity 70%, specificity 88%).
      For HbA1c, the best cut-off value was 42 mmol/mol (6.0%) (sensitivity 94%,
      specificity 93%). CONCLUSIONS: HbA1c seems to be more reliable than OGTT for
      diabetes screening in overweight and obese children and adolescents. The optimal
      HbA1c threshold for identifying patients with diabetes was found to be 42
      mmol/mol (6.0%). What is Known: * The prevalence of obesity is increasing and
      health problems related to type 2 DM can be serious. However, an optimal
      screening test for diabetes in obese youth seems to be controversial in the
      literature. What is New: * In our study, the ROC analysis revealed for FPG an
      optimal threshold of 98 mg/dl (5.4 mmol/l, sensitivity 70%, specificity 88%) and
      for HbA1c a best cut-off value of 42 mmol/mol (6.0%, sensitivity 94%, specificity
      93%) to detect diabetes. Thus, in overweight and obese children and adolescents,
      HbA1c seems to be a more reliable screening tool than OGTT.

PMID- 27888414
TI  - Structural brain abnormalities in patients with vestibular migraine.
AB  - New advances in understanding the pathophysiology of vestibular migraine (VM)
      have suggested a large overlap between migraine and vestibular pathways. We
      explored the regional distribution of gray (GM) and white matter (WM)
      abnormalities in VM patients in comparison to migraine patients with (MWA) and
      without aura (MWoA) and their correlations with patients' clinical
      manifestations. Using a 3.0 Tesla scanner, brain T2-weighted and 3D T1-weighted
      MRI scans were acquired from 19 VM, 19 MWA, 19 MWoA and 20 age-matched controls.
      GM and WM volumetric abnormalities were estimated using voxel-based morphometry
      (SPM12). Compared to controls, migraine patients had decreased GM volume of the
      left cerebellum and an increased GM volume of the left temporal lobe. VM patients
      had a selective GM volume increase of frontal and occipital regions compared to
      controls and the other two groups of migraineurs and no regions with decreased GM
      volume. Compared to MWoA and MWA, VM had increased GM volume of the left
      thalamus. Regional GM abnormalities did not correlate with disease duration and
      attack frequency. No WM volumetric differences were detected between migraine
      patients and controls. These results show that GM volume abnormalities of
      nociceptive and multisensory vestibular brain areas occur in VM patients.
      Overall, our findings suggest that an abnormal brain sensitization might lead to
      a dismodulation of multimodal sensory integration and processing cortical areas
      in VM patients.

PMID- 27888413
TI  - Improving manual oxygen titration in preterm infants by training and guideline
      implementation.
AB  - : To study oxygen saturation (SpO2) targeting before and after training and
      guideline implementation of manual oxygen titration, two cohorts of preterm
      infants <30 weeks of gestation needing respiratory support and oxygen therapy
      were compared. The percentage of the time spent with SpO2 within the target range
      (85-95%) was calculated (%SpO2-wtr). SpO2 was collected every minute when oxygen
      is >21%. ABCs where oxygen therapy was given were identified and analyzed. After
      training and guideline implementation the %SpO2-wtr increased (median
      interquartile range (IQR)) 48.0 (19.6-63.9) % vs 61.9 (48.5-72.3) %; p < 0.005,
      with a decrease in the %SpO2 > 95% (44.0 (27.8-66.2) % vs 30.8 (22.6-44.5) %; p <
      0.05). There was no effect on the %SpO2 < 85% (5.9 (2.8-7.9) % vs 6.2 (2.5-8) %;
      ns) and %SpO2 < 80% (1.9 (1.0-3.0) % vs 1.7 (0.8-2.6) %; ns). In total, 186 ABCs
      with oxygen therapy before and 168 ABCs after training and guideline
      implementation occurred. The duration of SpO2 < 80% reduced (2 (1-2) vs 1 (1-2)
      minutes; p < 0.05), the occurrence of SpO2 > 95% did not decrease (73% vs 64%;
      ns) but lasted shorter (2 (0-7) vs 1 (1-3) minute; p < 0.004). CONCLUSION:
      Training and guideline implementation in manual oxygen titration improved SpO2
      targeting in preterm infants with more time spent within the target range and
      less frequent hyperoxaemia. The durations of hypoxaemia and hyperoxaemia during
      ABCs were shorter. What is Known: * Oxygen saturation targeting in preterm
      infants can be challenging and the compliance is low when oxygen is titrated
      manually. * Hyperoxaemia often occurs after oxygen therapy for oxygen
      desaturation during apnoeas. What is New: * Training and implementing guidelines
      improved oxygen saturation targeting and reduced hyperoxaemia. * Training and
      implementing guidelines improved manual oxygen titration during ABC.

PMID- 27888415
TI  - Magnetic resonance imaging patterns of muscle involvement in genetic muscle
      diseases: a systematic review.
AB  - A growing body of the literature supports the use of magnetic resonance imaging
      as a potential biomarker for disease severity in the hereditary myopathies. We
      performed a systematic review of the medical literature to evaluate patterns of
      fat infiltration observed in magnetic resonance imaging studies of muscular
      dystrophy and congenital myopathy. Searches were performed using MEDLINE, EMBASE,
      and grey literature databases. Studies that described fat infiltration of muscles
      in patients with muscular dystrophy or congenital myopathy were selected for full
      length review. Data on preferentially involved or spared muscles were extracted
      for analysis. A total of 2172 titles and abstracts were screened, and 70
      publications met our criteria for inclusion in the systematic review. There were
      23 distinct genetic disorders represented in this analysis. In most studies,
      preferential involvement and sparing of specific muscles were reported. We
      conclude that magnetic resonance imaging studies can be used to identify distinct
      patterns of muscle involvement in the hereditary myopathies. However, larger
      studies and standardized methods of reporting are needed to develop imaging as a
      diagnostic tool in these diseases.

PMID- 27888417
TI  - Acute pneumonitis and pericarditis related to alemtuzumab therapy in relapsing
      remitting multiple sclerosis.

PMID- 27888416
TI  - Lesion remyelinating activity of GSK239512 versus placebo in patients with
      relapsing-remitting multiple sclerosis: a randomised, single-blind, phase II
      study.
AB  - Histamine H3 receptor blockade may enhance lesion remyelination in multiple
      sclerosis (MS). The efficacy (using a magnetic resonance imaging marker of
      myelination, magnetisation transfer ratio [MTR]), safety and pharmacokinetics of
      GSK239512, a potent and brain penetrant H3 receptor antagonist/inverse agonist on
      lesion remyelination in relapsing-remitting MS (RRMS) were assessed. This was a
      phase II, randomised, parallel-group, placebo-controlled, double-blind (sponsor
      unblinded), international, multicentre study (NCT01772199). Patients aged 18-50
      with RRMS, receiving intramuscular interferon-beta1a or glatiramer acetate, were
      randomised 1:1 to once-daily oral GSK239512 or placebo, up-titrated over 4-5
      weeks to a maximum tolerable dose up to 80 ug and maintained until Week 48. The
      co-primary endpoints were mean changes in post-lesion MTR in gadolinium-enhanced
      (GdE) or Delta-MTR defined lesions from pre-lesion values. Adverse events (AE)
      and withdrawals were monitored. Of the 131 patients randomised, 114 patients
      completed the study (GSK239512, n = 51; placebo, n = 63) and 27 (GSK239512) and
      28 (placebo) patients contributed lesions to the primary analysis. GSK239512 was
      associated with positive effect sizes of 0.344 [90% confidence interval (CI)
      0.018, 0.671] and 0.243 (90% CI -0.112, 0.598) for adjusted mean changes in the
      normalised MTR for GdE and Delta-MTR lesions, respectively. The overall incidence
      of AEs was similar between GSK239512 and placebo during the treatment phase
      although some AEs including insomnia were more common with GSK239512,
      particularly during the titration period. A small but positive effect of
      GSK239512 on remyelination was observed. MTR assessment represents a promising
      method for detecting lesion remyelination in RRMS.

PMID- 27888418
TI  - Suppression of mTOR signaling pathway promotes bone marrow mesenchymal stem cells
      differentiation into osteoblast in degenerative scoliosis: in vivo and in vitro.
AB  - To investigate the role of mTOR signaling pathway in bone marrow mesenchymal stem
      cells (BMSCs) differentiation into osteoblast in degenerative scoliosis (DS). The
      rat model of DS was established. Thirty-two Sprague-Dawley (SD) rats were
      selected and divided into the normal control group, the positive control group
      (normal rats injected with rapamycin), the negative control group (DS rats
      injected with PBS) and the experiment group (DS rats injected with rapamycin).
      H&E staining was performed to observe the osteogenesis of scoliosis. The BMSCs
      were obtained and assigned into seven groups: the normal control group, the
      positive control group, the negative control group and 1.0/10.0/100.0/1000.0
      nmol/L experiment groups. Flow cytometry was conducted to testify cell cycle. The
      mRNA and protein expressions of mTOR and osteoblastic differentiation markers
      were measured by qRT-PCR and western blotting. In vivo, compared with the
      negative control group, bone trabecular area and the number of differentiated
      bone cells were significantly increased in the experiment groups. In vitro, at 24
      and 48 h after rapamycin treatment, compared with the negative control group,
      BMSCs at G0/G1 stage increased, but BMSCs at S stage decreased in the
      1.0/10.0/100.0/1000.0 nmol/L experiment groups; the expressions of mTOR and p70
      S6K1 proteins were reduced in the 1.0/10.0/100.0/1000.0 nmol/L experiment groups,
      while ALP activity, OC levels, calcium deposition, Co1-I protein expression and
      the mRNA expressions of OC and Co1-I were significantly increased. Suppression of
      mTOR signaling pathway by rapamycin could promote BMSCs differentiation into
      osteoblast in DS.

PMID- 27888420
TI  - Endocan as a prognostic biomarker of triple-negative breast cancer.
AB  - PURPOSE: Triple-negative breast cancer (TNBC) has aggressive characteristics and
      fewer treatment options than other subtypes. The purpose of this study was to
      explore prognostic biomarkers for TNBC that can be easily detected from the blood
      samples. METHODS: MDA-MB-231 and MDA-MB-231BR, a brain metastatic variant of the
      human TNBC cell line MDA-MB-231, were used as less and more aggressive models of
      TNBC, respectively. The extent to which the candidate gene/protein identified by
      RNA sequencing correlated well with aggressiveness of TNBC and how much protein
      was detected from the blood of tumor-bearing mice were evaluated. RESULTS: Both
      the in vitro proliferation and in vivo tumor growth of MDA-MB-231BR were more
      rapid than those of MDA-MB-231. RNA sequencing identified ESM1 as a gene that was
      expressed significantly more in MDA-MB-231BR than in MDA-MB-231, and qRT-PCR
      confirmed a significantly higher expression of ESM1 in MDA-MB-231BR xenograft in
      vivo. Furthermore, Kaplan-Meier analysis of relapse-free survival demonstrated
      that TNBC patients with high ESM1 expression had clearly worse relapse-free
      survival than those with low ESM1 expression, which was consistent with our
      preclinical findings. Endocan, a protein of ESM1 gene product, was successfully
      detected in both conditioned medium from MDA-MB-231BR and plasma samples from
      mice bearing MDA-MB-231BR xenograft, which showed a significantly distinct
      pattern from less aggressive MDA-MB-231. Moreover, bisulfite sequence analysis
      revealed that overexpression of ESM1 in MDA-MB-231BR might be attributed to DNA
      demethylation in an upstream region of the ESM1 gene. CONCLUSION: This study
      indicates that endocan could be used as a blood-based prognostic biomarker in
      TNBC patients.

PMID- 27888421
TI  - Triple-negative breast cancer has worse overall survival and cause-specific
      survival than non-triple-negative breast cancer.
AB  - PURPOSE: The current American Joint Committee on Cancer (AJCC) staging manual
      uses tumor size, lymph node, and metastatic status to stage breast cancer across
      different subtypes. We examined the prognosis of triple-negative breast cancer
      (TNBC) versus non-TNBC within the same stages and sub-stages to evaluate whether
      TNBC had worse prognosis than non-TNBC. METHODS: We reviewed the National Cancer
      Institute Surveillance, Epidemiology, and End Results (SEER) data and identified
      158,358 patients diagnosed with breast cancer from 2010 to 2012. The overall
      survival (OS) time and breast cancer cause-specific survival time were compared
      between patients with TNBC and non-TNBC in each stage and sub-stages. The results
      were validated using a dataset of 2049 patients with longer follow-up from our
      institution. RESULTS: Compared with patients with non-TNBC, patients with TNBC
      had worse OS and breast cancer cause-specific survival time in every stage and
      sub-stage in univariate and multivariate analyses adjusting for age, race, tumor
      grade, and surgery and radiation treatments in the SEER data. The worse OS time
      in patients with TNBC was validated in our institutional dataset. CONCLUSIONS:
      Patients with TNBC have worse survival than patients with non-TNBC. The new AJCC
      staging manual should consider breast cancer biomarker information.

PMID- 27888419
TI  - Unravelling cardiovascular disease using four dimensional flow cardiovascular
      magnetic resonance.
AB  - Knowledge of normal and abnormal flow patterns in the human cardiovascular system
      increases our understanding of normal physiology and may help unravel the complex
      pathophysiological mechanisms leading to cardiovascular disease. Four-dimensional
      (4D) flow cardiovascular magnetic resonance (CMR) has emerged as a suitable
      technique that enables visualization of in vivo blood flow patterns and
      quantification of parameters that could potentially be of prognostic value in the
      disease process. In this review, current image processing tools that are used for
      comprehensive visualization and quantification of blood flow and energy
      distribution in the heart and great vessels will be discussed. Also, imaging
      biomarkers extracted from 4D flow CMR will be reviewed that have been shown to
      distinguish between normal and abnormal flow patterns. Furthermore, current
      applications of 4D flow CMR in the heart and great vessels will be discussed,
      showing its potential as an additional diagnostic modality which could aid in
      disease management and timing of surgical intervention.

PMID- 27888422
TI  - Enzymatic activities for lignin monomer intermediates highlight the biosynthetic
      pathway of syringyl monomers in Robinia pseudoacacia.
AB  - Most of the known 4-coumarate:coenzyme A ligase (4CL) isoforms lack CoA-ligation
      activity for sinapic acid. Therefore, there is some doubt as to whether sinapic
      acid contributes to sinapyl alcohol biosynthesis. In this study, we characterized
      the enzyme activity of a protein mixture extracted from the developing xylem of
      Robinia pseudoacacia. The crude protein mixture contained at least two 4CLs with
      sinapic acid 4-CoA ligation activity. The crude enzyme preparation displayed
      negligible sinapaldehyde dehydrogenase activity, but showed ferulic acid 5
      hydroxylation activity and 5-hydroxyferulic acid O-methyltransferase activity;
      these activities were retained in the presence of competitive substrates
      (coniferaldehyde and 5-hydroxyconiferaldehyde, respectively). 5-Hydroxyferulic
      acid and sinapic acid accumulated in the developing xylem of R. pseudoacacia,
      suggesting, in part at least, sinapic acid is a sinapyl alcohol precursor in this
      species.

PMID- 27888423
TI  - Assessment of land use and land cover change using spatiotemporal analysis of
      landscape: case study in south of Tehran.
AB  - In the recent years, dust storms originating from local abandoned agricultural
      lands have increasingly impacted Tehran and Karaj air quality. Designing and
      implementing mitigation plans are necessary to study land use/land cover change
      (LUCC). Land use/cover classification is particularly relevant in arid areas.
      This study aimed to map land use/cover by pixel- and object-based image
      classification methods, analyse landscape fragmentation and determine the effects
      of two different classification methods on landscape metrics. The same sets of
      ground data were used for both classification methods. Because accuracy of
      classification plays a key role in better understanding LUCC, both methods were
      employed. Land use/cover maps of the southwest area of Tehran city for the years
      1985, 2000 and 2014 were obtained from Landsat digital images and classified into
      three categories: built-up, agricultural and barren lands. The results of our
      LUCC analysis showed that the most important changes in built-up agricultural
      land categories were observed in zone B (Shahriar, Robat Karim and Eslamshahr)
      between 1985 and 2014. The landscape metrics obtained for all categories pictured
      high landscape fragmentation in the study area. Despite no significant difference
      was evidenced between the two classification methods, the object-based
      classification led to an overall higher accuracy than using the pixel-based
      classification. In particular, the accuracy of the built-up category showed a
      marked increase. In addition, both methods showed similar trends in fragmentation
      metrics. One of the reasons is that the object-based classification is able to
      identify buildings, impervious surface and roads in dense urban areas, which
      produced more accurate maps.

PMID- 27888424
TI  - Export of non-point source suspended sediment, nitrogen, and phosphorus from
      sloping highland agricultural fields in the East Asian monsoon region.
AB  - Excess sediment and nutrient export from agricultural fields with steep slopes is
      a major concern linked to surface water quality in Korea. In this study, the
      export of suspended sediment (SS), total nitrogen (TN), and total phosphorus (TP)
      and their event mean concentrations (EMCs) in surface runoff from a highland
      mixed land use (61% forested, 30% cropped, 9% other) watershed were quantified.
      In 2007, the Korean Ministry of Environment (MoE) declared the study area as a
      priority region for non-point source (NPS) pollution management and initiated
      various best management practices (BMPs) in the study watershed. SS, TN, and TP
      concentrations in Mandae Stream were monitored for 5 years (2009-2013) to
      evaluate the effectiveness of BMPs. Average EMCs for SS, TN, and TP were as high
      as 986, 3.4 and 0.8 mg/L, respectively. The agricultural export coefficients of
      agricultural land in the study watershed for SS, TN, and TP were 5611, 171, and
      6.83 kg/ha/year, respectively. A comparison with results from other studies shows
      that both EMCs and agricultural export coefficients in the study watershed were
      much higher than most of the results reported for watersheds in other regions.
      The results show that sediment and nutrient export from intensive agriculture
      areas with steep slopes continue to be a major concern for the downstream
      reservoir, Lake Soyang. Remedial strategies should be directed towards
      controlling sources of SS, TN, and TP to improve downstream water quality in
      sloping highland agricultural areas in Korea.

PMID- 27888425
TI  - An overview on common aspects influencing the dissipation pattern of pesticides:
      a review.
AB  - The common aspects and processes influencing dissipation kinetics of pesticides
      are determinants of their fate in the environment. Nowadays, with increasing
      population, the demand for food and fodder crops has also increased. With the
      development in science and technology, the methods of controlling pests may
      improve, but the major role played by the environment cannot be altered, i.e. the
      environmental factors, climatic conditions, and geology of areas under
      cultivation. Plants play a crucial role in the dissipation kinetics, as they may
      vary in species and characteristics. Differences in physico-chemical properties,
      such as formulation, bioavailability, and efficacy of the pesticide, may result
      in variable dissipation patterns even under the same environmental conditions.
      While modelling the dissipation kinetics for any specific pesticide applied to
      any specific crop, each factor must be considered. This review focusses on the
      variability observed across common factors, i.e. environmental aspects, plant
      associated facts, and observed characteristics of chemical substances,
      influencing pesticide dissipation.

PMID- 27888427
TI  - Taiwanese medical students' narratives of intercultural professionalism dilemmas:
      exploring tensions between Western medicine and Taiwanese culture.
AB  - In an era of globalization, cultural competence is necessary for the provision of
      quality healthcare. Although this topic has been well explored in non-Western
      cultures within Western contexts, the authors explore how Taiwanese medical
      students trained in Western medicine address intercultural professionalism
      dilemmas related to tensions between Western medicine and Taiwanese culture. A
      narrative interview method was employed with 64 Taiwanese medical students to
      collect narratives of professionalism dilemmas. Noting the prominence of culture
      in students' narratives, we explored this theme further using secondary analysis,
      identifying tensions between Western medicine and Taiwanese culture and
      categorizing students' intercultural professionalism dilemmas according to
      Friedman and Berthoin Antal's 'intercultural competence' framework: involving
      combinations of advocacy (i.e., championing one's own culture) and inquiry (i.e.,
      exploring one's own and others' cultures). One or more intercultural dilemmas
      were identified in nearly half of students' professionalism dilemma narratives.
      Qualitative themes included: family relations, local policy, end-of-life care,
      traditional medicine, gender relations and Taiwanese language. Of the 62
      narratives with sufficient detail for further analysis, the majority demonstrated
      the 'suboptimal' low advocacy/low inquiry approach (i.e., withdrawal or
      inaction), while very few demonstrated the 'ideal' high advocacy/high inquiry
      approach (i.e., generating mutual understanding, so 'intercultural competence').
      Though nearly half of students' professionalism narratives concerned
      intercultural dilemmas, most narratives represented disengagement from
      intercultural dilemmas, highlighting a possible need for more attention on
      intercultural competence training in Taiwan. The advocacy/inquiry framework may
      help educators to address similar disconnects between Western medicine and non
      Western cultures in other contexts.

PMID- 27888426
TI  - Evaluation of herbicides action on plant bioindicators by genetic biomarkers: a
      review.
AB  - The use of pesticides has increased worldwide, owing to the demand for products
      of good quality and to satisfy a growing population. Herbicides represent almost
      half of the total amount of pesticides used. Although important to the reduction
      of costs and an increase of productivity, their indiscriminate use, as well as
      that of the other pesticides, is a global environmental problem, since they
      affect the living organisms. To evaluate the damage caused by herbicides to the
      environment, different organisms have been used as bioindicators, especially
      higher plants, due to several advantages. This is a literature review on
      herbicidal actions in plant bioindicators, as assessed by genetic biomarkers.
      Also, the present manuscript aimed to characterize the main organisms (Allium
      cepa, Vicia faba and Tradescantia spp.) and the most used biomarkers (mitotic
      index, chromosome aberrations, micronuclei, sister chromatid exchange and
      mutations). We concluded that herbicides induce cytotoxicity and genotoxicity in
      the assessed bioindicators. The data corroborate the existing warnings of the
      risks that the indiscriminate and increasing use of pesticides poses to the
      environment and its biodiversity.

PMID- 27888428
TI  - Investigating the role of implicit prototypes in the prototype willingness model.
AB  - One useful theory to predict health behavior is the prototype-willingness model
      (PWM), which posits that people are more willing to engage in behavior to the
      extent that they have a positive view of the prototypical person who performs
      that behavior. The goal of the present research is to test whether adding an
      implicit measure of prototype favorability might improve explanatory power in the
      PWM. Two studies examined whether implicit prototype favorability uniquely
      predicted White women's intentions to engage in healthy sun behavior over the
      next 3-6 months, and their willingness to engage in risky sun behavior, should
      the opportunity arise. The results suggested that implicit prototype
      favorability, particularly implicit prototypes of those who engage in risky UV
      related behaviors, uniquely predicted intentions to engage in healthy sun
      behavior and willingness to engage in risky sun behavior in the PWM.

PMID- 27888429
TI  - Inappropriateness of diagnostic imaging examinations in the inpatient setting: a
      case study research.
AB  - OBJECTIVE: The purpose of our study was to audit the clinical appropriateness of
      the prescriptions of whole body CT (WB-CT), PET-CT and chest X-rays (CXRs)
      performed at Tor Vergata University Hospital in the inpatient setting. MATERIALS
      AND METHODS: WB-CT, PET-CT and CXRs examinations were retrospectively analysed in
      the period between January and December 2014. CXR examinations were divided into
      bedside CXRs and traditional CXRs. The appropriateness of the examinations was
      defined according the American College of Radiology Appropriateness Criteria.
      Inappropriate examinations were divided into six inappropriateness categories in
      accordance with the European Union Medical Imaging Guidelines. RESULTS:
      Appropriateness was suboptimal for all analysed techniques CXRs (A = 38%, I =
      62%); bedside CXRs (A = 45%, I = 53%); WB-CT (A = 45%, I = 55%); PET-CT (A = 48%,
      I = 52%). With respect to WB-CT the highest rate of inappropriate imaging
      prescriptions came from the haematology clinical operative unit (OU) (44%) and
      emergency medicine (33%); with respect to PET-CT, the thoracic surgery OU (53%)
      and haematology OU (48%) showed the most inappropriate prescriptions. For CXRs,
      the percentage of inappropriateness was consistently distributed among all
      surgical OUs. For bedside CXRs, the largest inappropriate prescribers were the
      emergency medicine OU (48%), the cardiac surgery OU (58%), the intensive care OU
      (67%) and anaesthesia resuscitation OU (78%). The most represented classes of
      inappropriateness were 2, 3, 4 and 6. CONCLUSIONS: The elimination of
      inappropriate prescriptions would result in an annual savings of approximately
      390,000 Euro. An implementation plan to increase prescription appropriateness is
      under development by our group.

PMID- 27888430
TI  - Radiation exposure in diagnostic imaging: wisdom and prudence, but still a lot to
      understand.
AB  - Since 2000, a series of scientific articles on CT have been raising increasing
      concern about the risk of radiation induced cancer in children. The alarming
      conclusions of some of these articles had international echo through global
      media, provoking widespread public concern. Actually, many of these alarming
      scientific publications appeared to be flawed by poor study design, but their
      conclusions were not openly contradicted. In US and Europe pediatric radiologists
      had to face a huge challenge, which brought to the Image Gently campaign and the
      Eurosafe initiative with the aim to rebut misinformation and to support medical
      radiation protection. The Linear No Threshold model-which is the base of
      contemporary radioprotection-is increasingly questioned by new recent studies
      suggesting that low dose radiation would decrease cancer risk thanks to the
      enhancement of immune system response. Actually, pediatric radiologists have to
      cope with many important issues and contradictory messages. Good medical practice
      includes good communication about the benefits and risks of health procedures,
      thus the communication of radiation risk is a key component for radiologists.
      When considering benefits and risks, an important risk is too often ignored: the
      risk that skipping a diagnostic exam may cause a misdiagnosis, and therefore, a
      poor outcome. We should emphasize that a risk from a radiological investigation
      is very small, if a risk at all, and we are not sure that there is a risk at very
      low doses, like those doses in the majority of X-ray procedures including CT.

PMID- 27888432
TI  - Candidate predisposing germline copy number variants in early onset colorectal
      cancer patients.
AB  - PURPOSE: A great proportion of the heritability of colorectal cancer (CRC) still
      remains unexplained, and rare variants, as well as copy number changes, have been
      proposed as potential candidates to explain the so-called 'missing heritability'.
      We aimed to identify rare high-to-moderately penetrant copy number variants
      (CNVs) in patients suspected of having hereditary CRC due to an early onset.
      METHODS/PATIENTS: We have selected for genome-wide copy number analysis, 27 MMR
      proficient early onset CRC patients (<50 years) without identifiable germline
      mutations in Mendelian genes related to this phenotype. Rare CNVs were selected
      by removing all CNVs detected at MAF >1% in the in-house control CNV database (n
      = 629 healthy controls). Copy number assignment was checked by duplex real-time
      quantitative PCR or multiplex ligation probe amplification. Somatic mutation
      analysis in candidate genes included: loss of heterozygosity studies, point
      mutation screening, and methylation status of the promoter. RESULTS: We have
      identified two rare germline deletions involving the AK3 and SLIT2 genes in two
      patients. The search for a second somatic mutational event in the corresponding
      CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in
      SLIT2. Both genes have been previously related to colorectal carcinogenesis.
      CONCLUSIONS: These findings suggest that AK3 and SLIT2 may be potential
      candidates involved in genetic susceptibility to CRC.

PMID- 27888433
TI  - Clinical significance of incidentally detected bladder wall thickening on
      computed tomography.
AB  - PURPOSE: To evaluate the clinical significance of incidentally detected bladder
      wall thickening (BWT) on computed tomography (CT). METHODS: A retrospective
      analysis was performed on 34,793 cystoscopy cases between January 2004 and
      December 2013. Among these, patients who underwent cystoscopy for the sole
      indication of incidentally detected BWT on CT were selected. Patients were
      categorized into the diffuse or focal group depending on the extent of BWT.
      Suspicious lesions on cystoscopy were biopsied to confirm histologic subtype. The
      incidence and predictive factors of bladder malignancy were examined. RESULTS: A
      total of 167 (0.5%) patients received cystoscopy for incidentally detected BWT on
      CT, of which 11 (6.6%) patients were diagnosed with bladder malignancy. When a
      suspicious lesion was identified on cystoscopy, 11 of 25 (44%) patients were
      found to have a bladder malignancy. Of the 15 patients with diffuse BWT, 5
      (33.3%) were diagnosed with bladder malignancy, consisting of carcinoma in situ
      in 2 patients, high-grade carcinoma in 2 patients and muscle invasive disease in
      1 patient. Of the 10 patients with focal BWT, 6 (60.0%) were diagnosed with
      bladder malignancy, of which 3 patients had high-grade disease. On multivariate
      logistic regression analysis, focal BWT [95% confidence interval (CI) 1.400
      25.357, P = 0.016] and atypical cells in urine cytology (95% CI 2.631-63.446, P =
      0.002) were positively associated with bladder malignancy. CONCLUSIONS:
      Incidentally detected BWT on CT can be suggestive of bladder malignancy.
      Therefore, further work-up including cystoscopy and urine cytology should be
      performed to assess bladder malignancy.

PMID- 27888436
TI  - Erratum to: Clinical and Biological Principles of Cold Atmospheric Plasma
      Application in Skin Cancer.

PMID- 27888434
TI  - A novel heavy metal ATPase peptide from Prosopis juliflora is involved in metal
      uptake in yeast and tobacco.
AB  - Heavy metal pollution of agricultural soils is one of the most severe ecological
      problems in the world. Prosopis juliflora, a phreatophytic tree species, grows
      well in heavy metal laden industrial sites and is known to accumulate heavy
      metals. Heavy Metal ATPases (HMAs) are ATP driven heavy metal pumps that
      translocate heavy metals across biological membranes thus helping the plant in
      heavy metal tolerance and phytoremediation. In the present study we have isolated
      and characterized a novel 28.9 kDa heavy metal ATPase peptide (PjHMT) from P.
      juliflora which shows high similarity to the C-terminal region of P1B ATPase
      HMA1. It also shows the absence of the invariant signature sequence DKTGT, and
      the metal binding CPX motif but the presence of conserved regions like
      MVGEGINDAPAL (ATP binding consensus sequence), HEGGTLLVCLNS (metal binding
      domain) and MLTGD, GEGIND and HEGG motifs which play important roles in metal
      transport or ATP binding. PjHMT, was found to be upregulated under cadmium and
      zinc stress. Heterologous expression of PjHMT in yeast showed a higher
      accumulation and tolerance of heavy metals in yeast. Further, transgenic tobacco
      plants constitutively expressing PjHMT also showed increased accumulation and
      tolerance to cadmium. Thus, this study suggests that the transport peptide from
      P. juliflora may have an important role in Cd uptake and thus in
      phytoremediation.

PMID- 27888435
TI  - Increased sclerostin and bone turnover after diet-induced weight loss in type 2
      diabetes: a post hoc analysis of the MADIAB trial.
AB  - BACKGROUND: Sclerostin has been directly related to bone turnover increase in
      dietary-induced weight loss in non-diabetics. This has not been studied in type 2
      diabetes, a condition characterized by increased circulating sclerostin and
      impaired bone turnover. PURPOSE: To study the effect of dietary weight loss and
      quality of the dietary intervention on changes of sclerostin and bone turnover
      markers in type 2 diabetes. METHODS: This was a post-hoc analysis of the MADIAB
      trial, a 21-day randomized controlled trial on overweight/obese type 2 diabetes
      patients. Patients were randomly assigned 1:1 to the Ma-Pi2 macrobiotic diet or a
      control diet based on dietary guidelines for type 2 diabetes. Serum sclerostin
      and circulating markers of bone resorption and formation (P1NP) were measured by
      enzyme linked immunosorbent assay in 40 subjects (1:1) at baseline and after 21
      days treatment. RESULTS: Both Ma-Pi2 and the control diet groups had significant
      decreases in body weight (6.0 +/- 0.2 vs. 3.2 +/- 0.1 %, p < 0.001). Sclerostin
      increased significantly in the two groups (all p < 0.001) but Ma-Pi2 diet group
      experienced a greater increase in sclerostin (34.5 vs. 15 %; p = 0.024). Serum
      circulating markers of bone resorption increased in the two groups (all p <
      0.001); circulating markers of bone resorption at the end of the treatment tended
      to be higher in Ma-Pi2 diet than the control diet group (p = 0.06). P1NP did not
      change significantly in the two group compared to baseline. Sclerostin changes
      were related to body mass index reduction (r = -0.37; p = 0.02). CONCLUSIONS:
      Diet-induced weight loss may induce significant and rapid changes in bone
      turnover and sclerostin levels. These changes may further impair bone health in
      subjects with type 2 diabetes.

PMID- 27888437
TI  - Estimated Budget Impact of Adopting the Affordable Care Act's Required Smoking
      Cessation Coverage on United States Healthcare Payers.
AB  - INTRODUCTION: Despite abundant information on the negative impacts of smoking,
      more than 40 million adult Americans continue to smoke. The Affordable Care Act
      (ACA) requires tobacco cessation as a preventive service with no patient cost
      share for all FDA-approved cessation medications. Health plans have a vital role
      in supporting smoking cessation by managing medication access, but uncertainty
      remains on the gaps between smoking cessation requirements and what is actually
      occurring in practice. This study presents current cessation patterns, real-world
      drug costs and plan benefit design data, and estimates the 1- to 5-year pharmacy
      budget impact of providing ACA-required coverage for smoking cessation products
      to understand the fiscal impact to a US healthcare plan. METHODS: A closed cohort
      budget impact model was developed in Microsoft Excel(r) to estimate current and
      projected costs for US payers (commercial, Medicare, Medicaid) covering smoking
      cessation medicines, with assumptions for coverage and smoking cessation product
      utilization based on current, real-world national and state-level trends for
      hypothetical commercial, Medicare, and Medicaid plans with 1 million covered
      lives. A Markov methodology with five health states captures quit attempt and
      relapse patterns. Results include the number of smokers attempting to quit,
      number of successful quitters, annual costs, and cost per-member per-month
      (PMPM). RESULTS: The projected PMPM cost of providing coverage for smoking
      cessation medications is $0.10 for commercial, $0.06 for Medicare, and $0.07 for
      Medicaid plans, reflecting a low incremental PMPM impact of covering two attempts
      ranging from $0.01 for Medicaid to $0.02 for commercial and Medicare payers.
      CONCLUSION: The projected PMPM impact of covering two quit attempts with access
      to all seven cessation medications at no patient cost share remains low. Results
      of this study reinforce that the impact of adopting the ACA requirements for
      smoking cessation coverage will have a limited near-term impact on health plan's
      budgets. FUNDING: Pfizer Inc.

PMID- 27888439
TI  - Laparoscopic use of the Contour(r) Curved Cutter Stapler device via a glove port:
      a modified technique.

PMID- 27888438
TI  - Transanal hemorrhoidal dearterialization with mucopexy versus open
      hemorrhoidectomy in the treatment of hemorrhoids: a meta-analysis of randomized
      control trials.
AB  - BACKGROUND: The aim of this study was to analyse the outcomes of transanal
      hemorrhoidal dearterialization with mucopexy (THDm) versus open hemorrhoidectomy
      (OH) in the management of hemorrhoids. METHODS: Randomized controlled trials in
      English were found by searching PubMed, Web of science, EMBASE, and the Cochrane
      Library database. Trials that compared THDm with OH were identified. Data were
      extracted independently for each study, and a meta-analysis was performed using
      fixed and random effects models. RESULTS: Four trials, including 316 patients,
      met the inclusion criteria. No statistically significant differences were noted
      in either total complications or postoperative bleeding, incontinence, recurrent
      prolapse, and urinary retention rate. Operative time was significantly longer for
      THDm with Doppler guidance than for THDm without Doppler guidance. Patients
      returned to normal activities faster after THDm than after OH. No statistically
      significant differences between THDm and OH were noted with regard to recurrence
      and reoperation rates. CONCLUSIONS: Our meta-analysis shows that THDm and OH are
      equally effective and can be attempted for the management of hemorrhoids.
      However, for THDm with Doppler guidance, more instruments and a longer operative
      time are required. Future large-scale, high-quality, multicenter trials with long
      term outcomes are needed to prove these results and determine whether Doppler
      guidance in THD is truly necessary or not.

PMID- 27888440
TI  - Primary and repeated perineal stapled prolapse resection.
AB  - BACKGROUND: Previous studies of the outcome after perineal stapled prolapse
      resection (PSPR) have included a limited number of patients with a short follow
      up and high recurrence rates. The present study was designed to assess the
      initial results, complications, recurrence rate, and outcomes up to 4 years after
      PSPR, as well as the need for a repeated procedure. METHODS: Fifty-four
      consecutive patients with rectal prolapse (mean age 77.2 years, range 46-93
      years; n = 3 men) were selected for PSPR between May 2009 and February 2015.
      Prolapse length was measured at baseline and after surgery. Patients were asked
      to grade intensity of symptoms as a satisfaction score of 1-10, 10 representing
      being symptom-free. RESULTS: The mean operation time was 45.3 min (SD = 17.5,
      range 25-95 min). The mean rectal prolapse length was reduced significantly from
      9.5 cm (SD = 5.0, range 4-30 cm) to 1.2 cm (SD = 2.6, range 0-10 cm; p < 0.0001).
      Bleeding requiring surgical intervention occurred in two patients (3.7%).
      Postoperative satisfaction score increased from a mean of 2.2 (SD = 0.9) to a
      mean of 6.4 (SD = 2.8, p <= 0.0001). After a mean follow-up of 13.4 months (SD =
      14.1), six patients with recurrence underwent a new PSPR and five patients
      underwent colostomy, mainly because of incontinence, resulting in a recurrence
      rate of 20.4%. There were no complications after redo PSPR, and after a median of
      10-month follow-up (range 6-37), there were no recurrences. CONCLUSIONS: PSPR is
      a rather new surgical procedure for external rectal prolapse. Immediate
      complications are few and not serious. Although recurrences can be treated with a
      second PSPR, the operation may only be the best option for old and fragile
      patients with comorbidities and a short life expectancy.

PMID- 27888441
TI  - Comparison of conventional incision and drainage for pilonidal abscess versus
      novel endoscopic pilonidal abscess treatment (EPAT).

PMID- 27888442
TI  - Annulohpoxylotol A and B, new sesquiterpenoids from the endophytic fungus
      Annulohypoxylon truncatum, are natural NF-kappaB inhibitors.
AB  - Two sesquiterpenoids, annulohpoxylotol A and B, were isolated along with five
      sterols from an ethyl acetate extract of cultures of the endophytic fungus
      Annulohypoxylon truncatum growing on leaves of Zizania caduciflora. The
      structures of the isolated compounds were established using one-dimensional (1D)
      and two-dimensional (2D)-NMR and mass spectrometry. The nuclear factor-kappa B
      (NF-kappaB) inhibitory activities of the isolated compounds stimulated with tumor
      necrosis factor-alpha (TNF-alpha) were measured using a luciferase reporter
      system. Annulohpoxylotol A (1) significantly inhibited NF-kappaB activation in a
      dose-dependent manner, with an IC50 of 7.11 MUM, whereas annulohpoxylotol B (2)
      and ergone (7) moderately inhibited NF-kappaB transcriptional activity, with IC50
      values of 19.24 and 17.51 MUM, respectively.

PMID- 27888444
TI  - First Report of Raoiella indica (Hirst) (Acari: Tenuipalpide) in Southern Brazil.
AB  - The red palm mite (RPM), Raoiella indica (Hirst) (Acari: Tenuipalpidae), was
      found for the first time in the Parana State, in southern Brazil. The first
      observations occurred in September 2015, on strawberry (Fragaria * ananassa Duch)
      leaves, which is not considered a typical host plant of RPM. It is probable that
      its occurrence on this plant was serendipitous. Visual surveys for RPM were
      carried out on four typical host plants (banana, coconut, foxtail palm, and real
      palm), in five cities of the Parana State (Bela Vista do Paraiso, Londrina,
      Maringa, Marialva, and Sarandi). RPM was found on each of the four typical host
      plants, in each of the five cities. Our survey extends RPM occurrence to the
      southern region of Brazil and indicates that the pest could be widespread in the
      country.

PMID- 27888443
TI  - The Effect of Heat and Free Chlorine Treatments on the Surface Properties of
      Murine Norovirus.
AB  - Heat and free chlorine are among the most efficient and commonly used treatments
      to inactivate enteric viruses, but their global inactivation mechanisms have not
      been elucidated yet. These treatments have been shown to affect at least the
      capsid proteins of viruses and thus may affect the surface properties (i.e.
      electrostatic charge and hydrophobicity) of such particles. Our aim was to study
      the effects of heat and free chlorine on surface properties for a murine
      norovirus chosen as surrogate for human norovirus. No changes in the surface
      properties were observed with our methods for murine norovirus exposed to free
      chlorine. Only the heat treatment led to major changes in the surface properties
      of the virus with the expression of hydrophobic domains at the surface of the
      particles after exposure to a temperature of 55  degrees C. No modification of
      the expression of hydrophobic domains occurred after exposure to 60  degrees C,
      and the low hydrophobic state exhibited by infectious and inactivated particles
      after exposure to 60  degrees C appeared to be irreversible for inactivated
      particles only, which may provide a means to discriminate infectious from
      inactivated murine noroviruses. When exposed to a temperature of 72  degrees C or
      to free chlorine at a concentration of 50 mg/L, the genome became available for
      RNases.

PMID- 27888445
TI  - Squeezed helical elastica.
AB  - We theoretically study the conformations of a helical semi-flexible filament
      confined to a flat surface. This squeezed helix exhibits a variety of unexpected
      shapes resembling circles, waves or spirals depending on the material parameters.
      We explore the conformation space in detail and show that the shapes can be
      understood as the mutual elastic interaction of conformational quasi-particles.
      Our theoretical results are potentially useful to determine the material
      parameters of such helical filaments in an experimental setting.

PMID- 27888446
TI  - Cesarean section in the setting of severe pulmonary hypertension requiring
      extracorporeal life support.
AB  - We describe the use of veno-arterial extracorporeal membrane oxygenation (ECMO)
      in a 35-year-old female with severe fixed pulmonary hypertension who went into
      cardiogenic shock during a Cesarean section. Pregnancy in the presence of severe
      pulmonary hypertension is typically contraindicated due to high maternal
      mortality rates. This patient visited our hospital at 37 weeks of gestation after
      experiencing dyspnea and chest pain. Clinical evaluation revealed severe fixed
      pulmonary hypertension. At the time of the planned delivery, femoral lines were
      placed; in case of emergency, ECMO became necessary during the delivery. During
      delivery, the patient developed sudden hemodynamic collapse necessitating rapid
      cannulation and initiation of ECMO. She was stabilized pharmacologically and
      separated from ECMO after 2 days. The baby was delivered uneventfully, and the
      mother and child were discharged 1 month after delivery.

PMID- 27888448
TI  - A Randomized, Single-Blind Trial of Clobetasol Propionate 0.05% Cream Under
      Silicone Dressing Occlusion Versus Intra-Lesional Triamcinolone for Treatment of
      Keloid.
AB  - BACKGROUND AND OBJECTIVE: Keloid is conventionally treated with intra-lesional
      (IL) triamcinolone, which is highly operator dependent and has its own adverse
      effects. Topical steroid and silicone dressings are a patient friendly and non
      invasive treatment alternative. We therefore sought to determine the efficacy and
      safety of topical clobetasol propionate (Dermovate(r)) 0.05% cream under
      occlusion with Mepiform(r) silicone dressing compared to IL triamcinolone in the
      treatment of keloid. METHODS: This was a prospective, randomised, observer
      blinded study. Two keloids on the same site were randomly assigned to receive
      either daily topical clobetasol propionate 0.05% cream under occlusion with
      silicone dressing (Scar 1) or monthly IL triamcinolone injection (Scar 2).
      Efficacy was assessed using patient and observer scar assessment scale (POSAS) at
      4-weekly intervals up to 12 weeks. Dimension of keloid and adverse effects were
      also assessed. RESULTS: A total of 34 scars from 17 patients completed the study.
      There was significant improvement of POSAS at 12 weeks compared to baseline
      within each treatment group. However, there was no statistically significant
      difference in POSAS at 12 weeks between the two treatments. Keloid dimensions
      showed a similar trend of improvement by week 12 with either treatment (p = 0.002
      in Scar 1, p = 0.005 for Scar 2). However, there was no significant difference
      between the treatment. In the IL triamcinolone group, all patients reported pain
      and 70.6% observed necrotic skin reaction. There was a significantly higher rate
      of adverse effects such as erythema (41.2 vs. 17.6%), hypopigmentation (35.3 vs.
      23.5%), telangiectasia (41.2 vs. 17.6%) and skin atrophy (23.5 vs. 5.9%)
      documented in the IL triamcinolone group when compared to clobetasol propionate
      0.05% cream under occlusion with silicone dressing. CONCLUSION: Clobetasol
      propionate 0.05% cream under occlusion with silicone dressing is equally
      effective and has fewer adverse effects compared to IL triamcinolone. Hence, it
      may be used as an alternative treatment for keloid particularly in patients with
      low pain threshold, needle phobia and those who prefers home-based treatment.

PMID- 27888450
TI  - Effects of Chromium-Loaded Chitosan Nanoparticles on Glucose Transporter 4,
      Relevant mRNA, and Proteins of Phosphatidylinositol 3-Kinase, Akt2-Kinase, and
      AMP-Activated Protein Kinase of Skeletal Muscles in Finishing Pigs.
AB  - The study was conducted to evaluate the effects of chromium-loaded chitosan
      nanoparticles (Cr-CNP) on glucose transporter 4 (GLUT4), relevant messenger RNA
      (mRNA), and proteins involved in phosphatidylinositol 3-kinase (PI3K), Akt2
      kinase, and AMP-activated protein kinase (AMPK) of skeletal muscles in finishing
      pigs. A total of 120 crossbred barrows (BW 65.00 +/- 1.26 kg) were randomly
      allotted to four dietary treatments, with three pens per treatment and 10 pigs
      per pen. Pigs were fed the basal diet supplemented with 0, 100, 200, or 400
      MUg/kg of Cr from Cr-CNP for 35 days. After the feeding trials, 24 pigs were
      slaughtered to collect longissimus muscle samples for analysis. Cr-CNP
      supplementation increased GLUT4 messenger RNA (mRNA) (quadratically, P < 0.01)
      and total and plasma membrane GLUT4 protein contents (linearly and quadratically,
      P < 0.001) in skeletal muscles. Glycogen synthase kinase 3beta (GSK-3beta) mRNA
      was decreased linearly (P < 0.001) and quadratically (P < 0.001). Supplemental Cr
      CNP increased insulin receptor (InsR) mRNA quadratically (P < 0.01), Akt2 total
      protein level linearly (P < 0.01) and quadratically (P < 0.001), and PI3K total
      protein was increased significantly (P < 0.05) in 200 MUg/kg treatment group. The
      mRNA of AMPK subunit gamma-3 (PRKAG3) and protein of AMPKalpha1 was significantly
      increased (P < 0.001) with the addition of Cr-CNP. The results indicate that
      dietary supplementation of Cr-CNP may promote glucose uptake by leading to
      recruitment of GLUT4 to the plasma membrane in skeletal muscles, and these
      actions may be associated with the insulin signal transduction and AMPK.

PMID- 27888447
TI  - The regulation of the mitochondrial apoptotic pathway by glucocorticoid receptor
      in collaboration with Bcl-2 family proteins in developing T cells.
AB  - Glucocorticoids (GC) are important in the regulation of selection and apoptosis
      of CD4+CD8+ double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP
      thymocytes, observed earlier, might be due to the combination of classical
      (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling
      events modifying activation or apoptotic pathways. In particular, the previously
      demonstrated mitochondrial translocation of activated GR in DP thymocytes offered
      a fascinating explanation for their pronounced GC-induced apoptosis sensitivity.
      However, the fine molecular details how the mitochondrial translocation of GR
      might regulate apoptosis remained unclear. Therefore, in the present study, we
      intended to examine which apoptotic pathways could be involved in GC-induced
      thymocyte apoptosis. Furthermore we investigated the potential relationship
      between the GR and Bcl-2 proteins. Using an in vitro test system, thymocytes from
      4-week-old BALB/c mice, were treated with the GC-analogue dexamethasone (DX). Bax
      accumulated in mitochondria upon DX treatment. Mitochondrial GR showed
      association with members of the Bcl-2 family: Bak, Bim, Bcl-xL. Elevated
      Cytochrome C, and active caspase-3, -8, and -9 levels were detected in thymocytes
      after DX treatment. These results support the hypothesis that in early phases of
      GC-induced thymocyte apoptosis, the mitochondrial pathway plays a crucial role,
      confirmed by the release of Cytochrome C and the activation of caspase-9. The
      activation of caspase-8 was presumably due to cross-talk between apoptotic
      signaling pathways. We propose that the GC-induced mitochondrial accumulation of
      Bax and the interaction between the GR and Bim, Bcl-xL and Bak could play a role
      in the regulation of thymocyte apoptosis.

PMID- 27888449
TI  - Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective
      Effects.
AB  - Genus Salvia, commonly known as sage, is the largest genus in the Lamiaceae
      family. It comprises many species traditionally used as brain-enhancing tonics.
      In vitro and animal studies have confirmed that several Salvia species contain a
      large array of active compounds that may enhance cognitive activity and protect
      against neurodegenerative disease. In this review, the active constituents in
      plants belonging to the genus Salvia are summarised, and their influence on
      pharmacodynamics pertinent to cognitive activity are detailed. In particular, the
      effects of plants belonging to the genus Salvia and their constituents on
      cognitive skills including memory, attention and learning are detailed. Their
      potential effects in dementia, including Alzheimer's disease, are also examined.
      Completed human trials are summarised, and factors influencing the potency of
      Salvia plants are covered. Finally, directions for future research are proposed
      to enhance our understanding of the potential health benefits of Salvia plants.

PMID- 27888451
TI  - N-Acetyl-L-Cysteine Protects Liver and Kidney Against Chromium(VI)-Induced
      Oxidative Stress in Mice.
AB  - Acute hexavalent chromium [Cr(VI)] compound exposure may lead to hepatotoxic and
      nephrotoxic effects. Cr(VI) reduction may generate reactive intermediates and
      radicals which might be associated with damage. We investigated effects of N
      acetyl-l-cysteine (NAC) pre- or post-treatment on oxidative stress and
      accumulation of Cr in liver and kidney of Cr(VI)-exposed mice. Intraperitoneal
      potassium dichromate injection (20 mg Cr/kg) caused a significant elevation of
      lipid peroxidation in both tissues as compared to control (p < 0.05). Significant
      decreases in non-protein sulfhydryl (NPSH) level, as well as enzyme activities of
      catalase (CAT) and superoxide dismutase (SOD) along with significant accumulation
      of Cr in the tissues (p < 0.05) were of note. NAC pre-treatment (200 mg/kg, ip)
      provided a noticeable alleviation of lipid peroxidation (p < 0.05) in both
      tissues, whereas post-treatment exerted significant effect only in kidney.
      Similarly, Cr(VI)-induced NPSH decline was restored by NAC pre-treatment in both
      tissues (p < 0.05); however, NAC post-treatment could only replenish NPSH in
      liver (p < 0.05). Regarding enzyme activities, in liver tissue NAC pre-treatment
      provided significant restoration on Cr(VI)-induced CAT inhibition (p < 0.05),
      while SOD enzyme activity was regulated to some extent. In kidney, SOD activity
      was efficiently restored by both treatments (p < 0.05), whereas CAT enzyme
      alteration could not be totally relieved. Additionally, NAC pre-treatment in both
      tissues and post-treatment in liver exerted significant tissue Cr level decreases
      (p < 0.05). Overall, especially NAC pre-treatment seems to provide beneficial
      effects in regulating pro-oxidant/antioxidant balance and Cr accumulation caused
      by Cr(VI) in liver and kidney. This finding may be due to several mechanisms
      including extracellular reduction or chelation of Cr(VI) by readily available
      NAC.

PMID- 27888452
TI  - The Influence of the Dietary Cu-Glycine Complex on the Histomorphology of
      Cancellous Bone, Articular Cartilage, and Growth Plate as well as Bone Mechanical
      and Geometric Parameters Is Dose Dependent.
AB  - Copper (Cu) is required for all basic biochemical and physiological processes.
      The objective of this study was to compare the effect of two different chemical
      forms (sulfates and glycinate chelates also below the recommended dose) of Cu
      administered to adult rats on the biomechanical and morphometric properties of
      femur. Male rats at the age of 12 weeks were used in the 12-week experiment. The
      control diet provided the required Cu level from sulfate (S-Cu), and the other
      diets were supplemented with Cu-glycine complex. The Cu-Gly-treatment,
      irrespective of its concentration, did not influence the bone mass and length.
      The Cu-Gly-treatment in 100 and 75% of daily demand increased mechanical
      endurance. The Cu-Gly-treatment (regardless of its concentration) increased the
      real bone volume in epiphysis and decreased the total thickness and zone I of the
      articular cartilage compared to the control group supplemented with S-Cu. The Cu
      Gly-treatment enhanced the content of proteoglycans (except the OG50 group).
      Dietary Cu given to adult rats in the Cu-Gly complex covering the daily demand in
      75% exerted a positive effect on bone metabolism and appeared to be the most
      effective among the investigated doses of the organic form.

PMID- 27888453
TI  - Evaluation of nucleoside reverse transcriptase inhibitor dosing during continuous
      veno-venous hemofiltration.
AB  - Background Unpredictable drug concentrations may lead to suboptimal exposure to
      nucleoside reverse transcriptase inhibitors (NRTIs) due to inadequate doses
      administered during continuous veno-venous hemofiltration (CVVH), which in turn
      may lead to decreased antiretroviral efficacy and possibly further HIV disease
      progression. Objective To compare administered doses of NRTIs to calculated doses
      of NRTIs to evaluate if patients were expected to have a favorable
      pharmacokinetic exposure profile while receiving CVVH. Methods The NRTI dose was
      compared to a table of recommendations based on a mathematical formula that
      estimates the amount of drug expected to be removed during CVVH. Results Twelve
      patients were on 27 NRTIs. Eleven (41%) NRTI doses were expected to provide a
      favorable pharmacokinetic profile based on pharmacokinetic mathematical
      calculations. Conclusion The majority of NRTIs were potentially not optimally
      dosed based on proposed pharmacokinetic calculations.

PMID- 27888454
TI  - Availability and quality of illegitimate somatropin products obtained from the
      Internet.
AB  - Background Growth hormones are widely available on the Internet for those who
      want to enhance their physical performance and improve body satisfaction.
      Illegitimate websites market somatropin injections without medical prescription
      and encourage misuse. Customers potentially put their health at risk when
      purchasing parenteral medications online. Objective The objective of our study
      was to evaluate the online market of no-prescription somatropin products and to
      analyse and document Internet pharmacy characteristics, distribution and
      pharmaceutical quality. Setting Websites indexed in Google promoting somatropin
      for sale direct to patients. Method Websites promoting the sale of growth hormone
      products were identified and analysed from June to August 2014. Internet vendor
      sites were evaluated to identify possible patient and medication safety concerns.
      Website characteristics, delivery time, storage conditions, packaging and
      attached product information were assessed. Investigation of the somatropin
      content was achieved using capillary electrophoresis with UV detection and
      electrospray ionization mass spectrometry. Main outcome measure Accessibility and
      quality of somatropin injections. Results Seventeen individual Internet vendor
      websites distributed somatropin products directly to patients, majority (94%) did
      not require a valid medical prescription before dispensing the products. Majority
      (70%) of Internet pharmacies displayed no medical information and none (0%) of
      the vendors displayed any regulatory body logo. All online samples had
      significantly (p < 0.001) lower somatropin concentration than labelled.
      Conclusion Our results clearly illustrate that prescription only biologic drugs
      are widely available online and can be easily accessed by anyone. Unprofessional
      distribution and handling is likely to cause degradation and possible patient
      safety concerns.

PMID- 27888455
TI  - Modalities of Generalization Through Single Case Studies.
AB  - The value of case studies for theory building is still doubted in psychology. The
      paper argues for the importance of case studies and the possibility of
      generalizing from these for a specific sociocultural understanding of human
      development. The paper first clarifies the notion of abduction within case
      studies, drawing on pragmatists James and Peirce and expanding it with the work
      of Lewin, and argues that it is the core mechanism that allows generalization
      from case studies. The second section presents the possibility of generalizing
      from individual single case studies, for which not only the subjective
      perspective, but also the dynamics by which the social and cultural environment
      guide and enable the person's development, have to be accounted for. The third
      section elaborates the question of institutional case studies, where the
      challenge is to account both for institutional dynamics, and for persons'
      trajectories within; this is exemplified with an ongoing study on the process of
      obtaining citizenship in Switzerland. The paper briefly concludes by highlighting
      two possible implications of the paper, one concerning the process of theoretical
      reasoning, the other, the fact that sociocultural psychology could itself be seen
      as an institution in-the-making.

PMID- 27888456
TI  - Soil pH and electrical conductivity are key edaphic factors shaping bacterial
      communities of greenhouse soils in Korea.
AB  - Soil microorganisms play an essential role in soil ecosystem processes such as
      organic matter decomposition, nutrient cycling, and plant nutrient availability.
      The land use for greenhouse cultivation has been increasing continuously, which
      involves an intensive input of agricultural materials to enhance productivity;
      however, relatively little is known about bacterial communities in greenhouse
      soils. To assess the effects of environmental factors on the soil bacterial
      diversity and community composition, a total of 187 greenhouse soil samples
      collected across Korea were subjected to bacterial 16S rRNA gene pyrosequencing
      analysis. A total of 11,865 operational taxonomic units at a 97% similarity
      cutoff level were detected from 847,560 sequences. Among nine soil factors
      evaluated; pH, electrical conductivity (EC), exchangeable cations (Ca2+, Mg2+,
      Na+, and K+), available P2O5, organic matter, and NO3-N, soil pH was most
      strongly correlated with bacterial richness (polynomial regression, pH: R2 =
      0.1683, P < 0.001) and diversity (pH: R2 = 0.1765, P < 0.001). Community
      dissimilarities (Bray-Curtis distance) were positively correlated with Euclidean
      distance for pH and EC (Mantel test, pH: r = 0.2672, P < 0.001; EC: r = 0.1473, P
      < 0.001). Among dominant phyla (> 1%), the relative abundances of Proteobacteria,
      Gemmatimonadetes, Acidobacteria, Bacteroidetes, Chloroflexi, and Planctomycetes
      were also more strongly correlated with pH and EC values, compared with other
      soil cation contents, such as Ca2+, Mg2+, Na+, and K+. Our results suggest that,
      despite the heterogeneity of various environmental variables, the bacterial
      communities of the intensively cultivated greenhouse soils were particularly
      influenced by soil pH and EC. These findings therefore shed light on the soil
      microbial ecology of greenhouse cultivation, which should be helpful for devising
      effective management strategies to enhance soil microbial diversity and improving
      crop productivity.

PMID- 27888457
TI  - Korean indigenous bacterial species with valid names belonging to the phylum
      Actinobacteria.
AB  - To understand the isolation and classification state of actinobacterial species
      with valid names for Korean indigenous isolates, isolation source, regional
      origin, and taxonomic affiliation of the isolates were studied. At the time of
      this writing, the phylum Actinobacteria consisted of only one class,
      Actinobacteria, including five subclasses, 10 orders, 56 families, and 330
      genera. Moreover, new taxa of this phylum continue to be discovered. Korean
      actinobacterial species with a valid name has been reported from 1995 as
      Tsukamurella inchonensis isolated from a clinical specimen. In 1997, Streptomyces
      seoulensis was validated with the isolate from the natural Korean environment.
      Until Feb. 2016, 256 actinobacterial species with valid names originated from
      Korean territory were listed on LPSN. The species were affiliated with three
      subclasses (Acidimicrobidae, Actinobacteridae, and Rubrobacteridae), four orders
      (Acidimicrobiales, Actinomycetales, Bifidobacteriales, and Solirubrobacterales),
      12 suborders, 36 families, and 93 genera. Most of the species belonged to the
      subclass Actinobacteridae, and almost of the members of this subclass were
      affiliated with the order Actinomycetales. A number of novel isolates belonged to
      the families Nocardioidaceae, Microbacteriaceae, Intrasporangiaceae, and
      Streptomycetaceae as well as the genera Nocardioides, Streptomyces, and
      Microbacterium. Twenty-six novel genera and one novel family, Motilibacteraceae,
      were created first with Korean indigenous isolates. Most of the Korean indigenous
      actionobacterial species were isolated from natural environments such as soil,
      seawater, tidal flat sediment, and fresh-water. A considerable number of species
      were isolated from artificial resources such as fermented foods, wastewater,
      compost, biofilm, and water-cooling systems or clinical specimens. Korean
      indigenous actinobacterial species were isolated from whole territory of Korea,
      and especially a large number of species were from Jeju, Gyeonggi, Jeonnam,
      Daejeon, and Chungnam. A large number of novel actinobacterial species continue
      to be discovered since the Korean government is encouraging the search for new
      bacterial species and researchers are endeavoring to find out novel strains from
      extreme or untapped environments.

PMID- 27888458
TI  - Helicobacter pylori outer membrane protein, HomC, shows geographic dependent
      polymorphism that is influenced by the Bab family.
AB  - The array of outer membrane proteins (OMPs) found in Helicobacter pylori provides
      a crucial component for persistent colonization within the gastric niche. Not
      only does H. pylori harbor a wide number of OMPs, but these OMPs often vary
      across strains; this likely contributes to immune evasion, adaptation during long
      term colonization, and potentially differential disease progression. Previous
      work from our group described OMP differences among the Bab family (babA, babB,
      and babC) and Hom family (homA and homB) from 80 American H. pylori clinical
      isolates (AH) and 80 South Korean H. pylori clinical isolates (KH). In the
      current study, we expanded our investigation to include the less well
      characterized Hom family member, HomC.Overall, we identified and genotyped three
      homC variants: homC S , homC L , and homC M , in both populations. Similar to
      other polymorphic genes, the KH group showed less overall diversity, with 97.5%
      of strains harboring homC L . In contrast, a more heterogeneous profile was
      observed in strains derived from an American population; we found nearly equal
      distribution of homC S and homC L . Further analysis of the AH group identified
      associations between homC polymorphism and bab genotype; in AH strains, there was
      a significant association between homC L and carriage of babA at locus A. Since
      babA is an important virulence factor for the development of severe gastric
      disease, these data may suggest that homC polymorphism plays a role in H. pylori
      pathogenesis.

PMID- 27888459
TI  - Comparative analysis of bacterial diversity in the rhizosphere of tomato by
      culture-dependent and -independent approaches.
AB  - The microbiome in the rhizosphere-the region surrounding plant roots-plays a key
      role in plant growth and health, enhancing nutrient availability and protecting
      plants from biotic and abiotic stresses. To assess bacterial diversity in the
      tomato rhizosphere, we performed two contrasting approaches: culture-dependent
      and -independent. In the culture-dependent approach, two culture media
      (Reasoner's 2A agar and soil extract agar) were supplemented with 12 antibiotics
      for isolating diverse bacteria from the tomato rhizosphere by inhibiting
      predominant bacteria. A total of 689 bacterial isolates were clustered into 164
      operational taxonomic units (OTUs) at 97% sequence similarity, and these were
      found to belong to five bacterial phyla (Proteobacteria, Actinobacteria,
      Bacteroidetes, Acidobacteria, and Firmicutes). Of these, 122 OTUs were retrieved
      from the antibiotic-containing media, and 80 OTUs were recovered by one specific
      antibiotic-containing medium. In the culture-independent approach, we conducted
      Illumina MiSeq amplicon sequencing of the 16S rRNA gene and obtained 19,215 high
      quality sequences, which clustered into 478 OTUs belonging to 16 phyla. Among the
      total OTUs from the MiSeq dataset, 22% were recovered in the culture collection,
      whereas 41% of OTUs in the culture collection were not captured by MiSeq
      sequencing. These results showed that antibiotics were effective in isolating
      various taxa that were not readily isolated on antibiotic-free media, and that
      both contrasting approaches provided complementary information to characterize
      bacterial diversity in the tomato rhizosphere.

PMID- 27888460
TI  - Metagenomic analysis reveals the contribution of anaerobic methanotroph-1b in the
      oxidation of methane at the Ulleung Basin, East Sea of Korea.
AB  - We have previously identified a sulfate methane transition zone (SMTZ) within the
      methane hydrate-bearing sediment in the Ulleung Basin, East Sea of Korea, and the
      presence of ANME-1b group in the sediment has been shown by phylogenetic analysis
      of a 16S rRNA gene. Herein, we describe taxonomic and functional profiling in the
      SMTZ sample by metagenomic analysis, comparing with that of surface sediment.
      Metagenomic sequences of 115 Mbp and 252 Mbp were obtained from SMTZ and surface
      sediments, respectively. The taxonomic profiling using BLASTX against the SEED
      within MG-RAST showed the prevalence of methanogens (19.1%), such as
      Methanosarcinales (12.0%) and Methanomicrobiales (4.1%) predominated within the
      SMTZ metagenome. A number of 185,200 SMTZ reads (38.9%) and 438,484 surface reads
      (62.5%) were assigned to functional categories, and methanogenesis-related reads
      were statistically significantly overrepresented in the SMTZ metagenome. However,
      the mapping analysis of metagenome reads to the reference genomes, most of the
      sequences of the SMTZ metagenome were mapped to ANME-1 draft genomes, rather than
      those of methanogens. Furthermore, the two copies of the methyl-coenzyme M
      reductase gene (mcrA) segments of the SMTZ metagenome were clustered with ANME-1b
      in the phylogenetic cluster. These results indicate that ANME-1b reads were miss
      annotated to methanogens due to limitation of database. Many of key genes
      necessary for reverse methanogenesis were present in the SMTZ metagenome, except
      for N 5,N 10-methenyl-H4MPT reductase (mer) and CoB-CoM heterodisulfide reductase
      subunits D and E (hdrDE). These data suggest that the ANME-1b represents the
      primary player the anaerobic methane oxidation in the SMTZ, of the methane
      hydrate-bearing sediment at the Ulleung Basin, East Sea of Korea.

PMID- 27888462
TI  - Deinococcus rubellus sp. nov., bacteria isolated from the muscle of antarctic
      fish.
AB  - Two new bacterial strains designated as Ant6T and Ant18 were isolated from the
      muscle of a fish which had been caught in the Antarctic Ocean. Both strains are
      Gram-stain-positive, catalase positive, oxidase negative, aerobic, and coccoid
      bacteria. Phylogenetic analysis based on the 16S rRNA gene sequences of strains
      Ant6T and Ant18 revealed that the strains Ant6T and Ant18 belong to the genus
      Deinococcus in the family Deinococcaceae in the class Deinococci. The highest
      degrees of sequence similarities of strains Ant6T and Ant18 were found with
      Deinococcus alpinitundrae LMG 24283T by 96.4% and 96.8%, respectively. Strain
      Ant6T exhibited a high level of DNA- DNA hybridization values with strain Ant18
      (82 +/- 0.6%). Chemotaxonomic data revealed that the predominant fatty acids were
      C17: 0 cyclo, 16:0, and feature 3 (C16:1 omega6c/omega7c) for both strains. A
      complex polar lipid profile consisted of major amounts of unknown
      phosphoglycolipids (PGL) and unknown aminophospholipid (APL). Based on the
      phylogenetic, phenotypic, and chemotaxonomic data, strains Ant6T (=KEMB 9004-169T
      =JCM 31434T) and Ant18 (=KEMB 9004-170) should be classified as a new species,
      for which the name Deinococcus rubellus sp. nov. is proposed.

PMID- 27888461
TI  - Inhibitory effects of bee venom and its components against viruses in vitro and
      in vivo.
AB  - Bee venom (BV) from honey bee (Apis Melifera L.) contains at least 18
      pharmacologically active components including melittin (MLT), phospholipase A2
      (PLA2), and apamin etc. BV is safe for human treatments dose dependently and
      proven to possess different healing properties including antibacterial and
      antiparasitidal properties. Nevertheless, antiviral properties of BV have not
      well investigated. Hence, we identified the potential antiviral properties of BV
      and its component against a broad panel of viruses. Co-incubation of non
      cytotoxic amounts of BV and MLT, the main component of BV, significantly
      inhibited the replication of enveloped viruses such as Influenza A virus (PR8),
      Vesicular Stomatitis Virus (VSV), Respiratory Syncytial Virus (RSV), and Herpes
      Simplex Virus (HSV). Additionally, BV and MLT also inhibited the replication of
      non-enveloped viruses such as Enterovirus-71 (EV-71) and Coxsackie Virus (H3).
      Such antiviral properties were mainly explained by virucidal mechanism. Moreover,
      MLT protected mice which were challenged with lethal doses of pathogenic
      influenza A H1N1 viruses. Therefore, these results provides the evidence that BV
      and MLT could be a potential source as a promising antiviral agent, especially to
      develop as a broad spectrum antiviral agent.

PMID- 27888464
TI  - Mycobiota of ground red pepper and their aflatoxigenic potential.
AB  - To investigate contamination of ground red pepper with fungi and mycotoxin, we
      obtained 30 ground red pepper samples from 15 manufacturers in the main chili
      pepper-producing areas in Korea. Fungal contamination was evaluated by spreading
      diluted samples on potato dextrose agar plates. The total fungi counts ranged
      from 0 to 7.3 * 103 CFU/g. In the samples, the genus Aspergillus had the highest
      incidence, while Paecilomyces was isolated most frequently. The next most
      frequent genera were Rhizopus, Penicillium, Cladosporium, and Alternaria. Within
      Aspergillus, A. ruber was predominant, followed by A. niger, A. amstelodami, A.
      ochraceus, A. terreus, A. versicolor, A. flavus, and A. fumigatus. The samples
      were analyzed for aflatoxins, ochratoxin A, and citrinin by ultra-perfomance
      liquid chromatography (UPLC) with a fluorescence detector. Ochratoxin A was
      detected from three samples at 1.03-2.08 MUg/kg, whereas no aflatoxins or
      citrinin were detected. To test the potential of fungal isolates to produce
      aflatoxin, we performed a PCR assay that screened for the norB-cypA gene for 64
      Aspergillus isolates. As a result, a single 800-bp band was amplified from 10 A.
      flavus isolates, and one Aspergillus sp. isolate. UPLC analyses confirmed
      aflatoxin production by nine A. flavus isolates and one Aspergillus sp. isolate,
      which produced total aflatoxins at 146.88-909.53 MUg/kg. This indicates that
      continuous monitoring of ground red pepper for toxigenic fungi is necessary to
      minimize mycotoxin contamination.

PMID- 27888463
TI  - Deinococcus sedimenti sp. nov. isolated from river sediment.
AB  - A novel Gram-positive, oval-shaped, non-motile bacterium designated strain 16F1LT
      was isolated from sediment collected from the Han River in Seoul, Republic of
      Korea. Based on the 16S rRNA gene sequence (1,448 bp), this strain was identified
      as a member of the genus Deinococcus that belongs to the class Deinococci.
      Similarities in the 16S rRNA gene sequence were shown with Deinococcus
      daejeonensis MJ27T (99.0%), D. grandis DSM 3963T (98.1%), D. radiotolerans C1T
      (97.5%), and D. caeni Ho-08T (97.2%). Strain 16F1LT was classified as a different
      genomic species from closely related Deinococcus members, based on less than 70%
      DNA-DNA relatedness. Genomic DNA G+C content of strain 16F1LT was 67.2 mol%.
      Strain 16F1LT was found to grow at temperatures of 10-37 degrees C (optimum 25
      degrees C) and pH 7-8 (optimum pH 7) on R2A medium, and was catalase-positive and
      oxidase-negative. Strain 16F1LT showed resistance to gamma radiation (D10 > 2
      kGy). In addition, this strain had the following chemotaxonomic characteristics:
      the major fatty acids were C15:1 omega6c and C16:1 omega7c; the polar lipid
      profile contained phosphoglycolipids, unknown aminophospholipids, an unknown
      aminoglycolipid, unknown aminolipids, an unknown glycolipid, an unknown
      phospholipid, and an unknown polar lipid; the major quinone was MK-8.
      Phylogenetic, genotypic, phenotypic, and chemotaxonomic characteristics indicated
      that strain 16F1LT represents a novel species within the genus Deinococcus, for
      which the name Deinococcus sedimenti sp. nov. is proposed. The type strain is
      16F1LT (=KCTC 33796T =JCM 31405T).

PMID- 27888465
TI  - Bacillus piscis sp. nov., a novel bacterium isolated from the muscle of the
      antarctic fish Dissostichus mawsoni.
AB  - In this paper, a new bacterial strain designated as 16MFT21T is isolated from the
      muscle of a fish caught in the Antarctic Ocean. Strain 16MFT21T is a Gram
      staining-positive, catalase-oxidase-positive, rod-shaped facultative-aerobic
      bacterium. The phylogenetic analysis that is based on the 16S-rRNA gene sequence
      of strain 16MFT21T revealed that it belongs to the genus Bacillus in the family
      Bacillaceae in the class Bacilli. The highest degrees of the sequence similarity
      of the strain 16MFT21T is with Bacillus licheniformis ATCC 14580T (96.6%) and
      Bacillus sonorensis NBRC 101234T (96.6%). The isolate formed a pale-yellow
      pigment, and it grew in the presence of 0% to 10% (w/v) NaCl (optimum at 2%
      NaCl), a pH of 6.0 to 10.0 (optimum pH from 7.0 to 8.0), and from 4 degrees C to
      30 degrees C (optimum at 30 degrees C). The major polar lipids consist of
      diphosphatidylglycerol (DPG) and phosphatidylglycerol (PG). The predominant fatty
      acids are iso-C15:0, anteiso-C15:0, iso-C17:0, and anteiso-C17:0. The main
      respiratory quinone is menaquinone-7 (MK-7), and based on the use of the meso
      diaminopimelic acid as the diagnostic diamino acid, the peptidoglycan cell-wall
      type is A1gamma. Based on the phylogenetic, phenotypic, and chemotaxonomic data,
      strain 16MFT21T (=KCTC 18866T =JCM 31664T) for which the name Bacillus piscis sp.
      nov. is proposed should be classified as a new species.

PMID- 27888466
TI  - The Expression of IGFBP6 after Spinal Cord Injury: Implications for Neuronal
      Apoptosis.
AB  - IGFBP6, a member of the insulin-like growth factor-binding proteins family that
      contains six high affinity IGFBPs, modulates insulin-like growth factor (IGF)
      activity and also showed an independent effect of IGF, such as growth inhibition
      and apoptosis. However, the role of IGFBP6 in spinal cord injury (SCI) remains
      largely elusive. In this study, we have performed an acute SCI model in adult
      rats and investigated the dynamic changes of IGFBP6 expression in the spinal
      cord. Our results showed that IGFBP6 was upregulated significantly after SCI,
      which was paralleled with the levels of apoptotic proteins p53 and active caspase
      3. Immunofluorescent labeling showed that IGFBP6 was co-localizated with active
      caspase-3 and p53 in neurons. To further investigate the function of IGFBP6, an
      apoptosis model was established in primary neuronal cells. When IGFBP6 was
      knocked down by specific short interfering RNA (siRNA), the protein levels of
      active caspase-3 and Bax as well as the number of apoptotic primary neurons were
      significantly decreased in our study. Taken together, our findings suggest that
      the change of IGFBP6 protein expression plays a key role in neuronal apoptosis
      after SCI.

PMID- 27888468
TI  - Reinforcement sensitivity and restrained eating: the moderating role of executive
      control.
AB  - PURPOSE: As the prevalence of overweight and obesity are still increasing, it is
      important to help individuals who encounter difficulty with losing weight. The
      current study was set out to further investigate characteristics of individuals
      who are highly motivated to restrict their food intake to lose weight, but fail
      to do so (i.e., restrained eaters). The motivation to lose weight might stem from
      high punishment sensitivity, whereas the failure to succeed in restricting food
      intake might be the result of high reward sensitivity. Thus, it was examined
      whether restrained eaters are characterized by both high reward sensitivity and
      high punishment sensitivity. Additionally, this is the first study to examine
      executive control as a potential moderator of this relationship. METHODS: Female
      undergraduates (N = 60) performed a behavioral measure of executive control, and
      completed the Restraint Scale to index level of restrained eating as well as two
      questionnaires on reinforcement sensitivity; the Behavioral Inhibition
      Scale/Behavioral Activation Scale, and the Sensitivity to Punishment and
      Sensitivity to Reward Questionnaire. RESULTS: There was a positive relationship
      between restrained eating and punishment sensitivity as indexed by both
      questionnaires. Reward sensitivity as measured by both indices was not directly
      related to restrained eating. Executive control moderated the relation between
      reward responsivity (but not reward-drive) and restrained eating; specifically in
      women with relatively weak executive control there was a positive relationship
      between reward responsivity and restrained eating behavior. CONCLUSION: In women
      with low executive control, restrained eating is associated with both heightened
      sensitivity to punishment and heightened responsivity to reward.

PMID- 27888467
TI  - OsWRKY80-OsWRKY4 Module as a Positive Regulatory Circuit in Rice Resistance
      Against Rhizoctonia solani.
AB  - BACKGROUND: Plant WRKY transcription factors play pivotal roles in diverse
      biological processes but most notably in plant defense response to pathogens.
      Sheath blight represents one of the predominant diseases in rice. However, our
      knowledge about the functions of WRKY proteins in rice defense against sheath
      blight is rather limited. RESULTS: Here we demonstrate that the expression of
      Oryza sativa WRKY80 gene (OsWRKY80) is rapidly and strongly induced upon
      infection of Rhizoctonia solani, the causal agent of rice sheath blight disease.
      OsWRKY80 expression is also induced by exogenous jasmonic acid (JA) and ethylene
      (ET), but not by salicylic acid (SA). OsWRKY80-GFP is localized in the nuclei of
      onion epidermal cells in a transient expression assay. Consistently, OsWRKY80
      exhibits transcriptional activation activity in a GAL4 assay in yeast cells.
      Overexpression of OsWRKY80 in rice plants significantly enhanced disease
      resistance to R. solani, concomitant with elevated expression of OsWRKY4, another
      positive regulator in rice defense against R. solani. Suppression of OsWRKY80 by
      RNA interference (RNAi), on the other hand, compromised disease resistance to R.
      solani. Results of yeast one-hybrid assay and transient expression assay in
      tobacco cells have revealed that OsWRKY80 specifically binds to the promoter
      regions of OsWRKY4, which contain W-box (TTGAC[C/T]) or W-box like (TGAC[C/T])
      cis-elements. CONCLUSIONS: We propose that OsWRKY80 functions upstream of OsWRKY4
      as an important positive regulatory circuit that is implicated in rice defense
      response to sheath blight pathogen R. solani.

PMID- 27888469
TI  - Paraneoplastic rhombencephalitis and cerebellitis preceded by isolated
      intractable vomiting.

PMID- 27888470
TI  - Mutation of the Ser18 phosphorylation site on the sole Saccharomyces cerevisiae
      UCS protein, She4, can compromise high-temperature survival.
AB  - Folding of the myosin head often requires the joint actions of Hsp90 and a
      dedicated UNC45, Cro1, She4 (UCS) domain-containing cochaperone protein.
      Relatively weak sequence conservation exists between the single UCS protein of
      simple eukaryotes (She4 in budding yeast) and the two UCS proteins of higher
      organisms (the general cell and smooth muscle UNC45s; UNC45-GC and UNC45-SM
      respectively). In vertebrates, UNC45-GC facilitates cytoskeletal function whereas
      the 55% identical UNC45-SM assists in the assembly of the contractile apparatus
      of cardiac and skeletal muscles. UNC45-SM, unlike UNC45-GC, shares with yeast
      She4 an IDSL sequence motif known to be a site of in vivo serine phosphorylation
      in yeast. Investigating this further, we found that both a non-phosphorylatable
      (S18A) and a phosphomimetic (S18E) mutant form of She4 could rescue the type 1
      myosin localisation and endocytosis defects of the yeast she4Delta mutant at 39 
      degrees C. Nevertheless, at higher temperature (45  degrees C), only She4 (S18A),
      not She4(S18E), could substantially rescue the cell lysis defect of she4Delta
      mutant cells. In the yeast two-hybrid system, the non-phosphorylatable S18A and
      S251A mutant forms of She4 and UNC45-SM still displayed the stress-enhanced in
      vivo interaction with Hsp90 seen with the wild-type She4 and UNC45-SM. Such high
      temperature enforcement to interaction was though lost with the phosphomimetic
      mutant forms (She4(S18E) and UNC45-SM (S251E)), an indication that
      phosphorylation might suppress these increases in She4/Hsp90 and UNC45-SM/Hsp90
      interaction with stress.

PMID- 27888471
TI  - The Role of Incarceration and Reentry on Colorectal Cancer Screening Among
      Formerly Incarcerated Black and Hispanic-Latino Men in New York City.
AB  - In the USA, the rate of incarceration has steadily increased from 1980 to 2010, a
      period called mass incarceration. Incarcerated individuals are now leaving the
      jail system in large numbers, the majority of whom are returning to low-income
      and Black and Hispanic-Latino communities. Although highly preventable,
      colorectal cancer (CRC) is a significant risk for minority and underserved men
      over the age of 50. Black men have the highest CRC incidence and mortality rates,
      which can be prevented and treated effectively when detected early, especially
      via colonoscopy. Hispanic-Latino men have the third highest CRC incidence rates
      and the fourth highest mortality rates. This qualitative study seeks to examine
      how the experience of incarceration and reintegration affects the awareness of
      CRC screening practices, the attitudes towards these services, the availability
      of services, and the frequency of CRC screening among the recently released Black
      and Hispanic-Latino men over the age of 50 in New York City.

PMID- 27888472
TI  - The Quality of Romanian Breast Cancer Websites: a Five-Year Longitudinal
      Assessment.
AB  - The Internet has become an important source of overall health information and
      seems to be the second common source of information used by patients in the
      process of decision-making before breast surgery. The goal of this study was to
      monitor Romanian breast cancer websites and their quality over a period of 5
      years. We evaluated a sample of 20 websites selected from Google's first search
      results pages using specific rating scores for e-health quality, completeness,
      accuracy, and potential risk, in 2011 and 2016, respectively. Only 15 (75%) of
      the websites in the 2011 sample were accessible in 2016 and only two (10%)
      retained real-life visibility (Google PageRank < 20). The mean quality scores at
      baseline (2011) and follow-up (2016), respectively, were as follows: e-health
      quality 3.80 vs. 4.05; completeness 4.23 vs. 5.43; accuracy 5.74 vs. 6.35; and
      potential risk score 7.60 vs. 7.30. All quality scores were low or, at best,
      modest and did not improve significantly over the 5-year period. The results of
      the study draw attention to the need for programs aiming to improve the ability
      of breast cancer patients to screen the online health resources and to better
      regulate the medical Internet to safeguard the best interest of health
      information seekers.

PMID- 27888474
TI  - Colorectal surgery in elderly patients: our experience with DaVinci Xi(r) System.
AB  - BACKGROUND: Robotic technology for colorectal surgery was introduced by Weber in
      2002 to improve the benefits of the minimally invasive surgery already offered by
      the laparoscopic approach. AIMS: To evaluate the feasibility and the efficacy of
      the application of robotic surgery in elderly patients affected by colorectal
      diseases. METHODS: We reported the outcomes obtained during our first 50
      colorectal robotic surgical performances with DaVinci Xi(r) System, and we
      compared the results assessed for patients younger or older than 70 years.
      RESULTS: We examined 28 patients younger and 22 older than 70 years who underwent
      colorectal robotic surgery in our institution from September 2014 to June 2016.
      We performed 15 right colectomies, 20 left colectomies, 15 rectal resections.
      Mean ASA score was significantly higher in the Elderly Group. No statistically
      significant differences have been revealed in terms of post-operative morbidity,
      hospital stay, first diet intake, first flatus canalization and oncological
      outcome. DISCUSSION: According to the prolonged operative time, robotic
      technology was initially reserved to young patients with good performance status
      in order to avoid systemic failures in elderly patients suffering from pre
      existent comorbidities. Otherwise, once robotic approach safety and benefits in
      terms of better systemic outcomes were demonstrated, it started to be performed
      in elderly patients with satisfactory outcomes. CONCLUSION: Our experience
      revealed that robotic surgical approach is safe, feasible and offers many
      systemic benefits in elderly patients also with high ASA score. Age alone has not
      to be considered as exclusion criteria for robotic approach.

PMID- 27888473
TI  - Nasal mucosa healing after endoscopic sinus surgery in chronic rhinosinusitis of
      elderly patients: role of topic alpha-tocopherol acetate.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) in European country ranges in elderly
      patients from 4.5 to 12% of population and has a significant effect on quality of
      life. In these patients, rhinosinusitis is linked to immune functions changes
      with age and to mucosal paraphysiological alterations such as crusting formations
      with atrophic epithelium, variations of nasal airflow and modifications of the
      mucociliary clearance. Failure of medical treatments leads to surgery in patients
      with persistent symptoms and radiographic signs of CRS. The choice of appropriate
      post-surgical topic treatments is important for healing time and for preventing
      mucosal complications such as synechiae, crusting formation and atrophy with
      secondary bacterial and fungal infections. AIMS: Defining the effects of topic
      alpha-tocopherol acetate administration on nasal mucosa healing after endoscopic
      sinus surgery in CRS of elderly patients. METHODS: In this study were included 32
      patients, mean age 68.6, who underwent FESS because affected by CRS not
      responsive to medical treatments. After surgical treatment, we distinguish two
      groups basing on local nasal therapy. RESULTS: We investigated, in the
      postoperative time, the role of alpha-tocopherol acetate compared to gomenol oil.
      Follow-up was performed at 7-15 days and 1-3 months after surgery. We evaluated
      mucosal restoration using Rhinoscopy Sum Score and quality of life using Nasal
      Six Items Symptom Questionnaire. We observed a faster healing time and less
      recurrence of complications in patients who underwent topic treatment with alpha
      tocopherol acetate. DISCUSSION: In our research, we observed that alpha
      tocopherol acetate has no contraindications and side effects. CONCLUSIONS: Our
      study showed the effectiveness of alpha-tocopherol acetate topic treatment in
      elderly patients affected by CRS after FESS, in improving and speeding up the
      process of restoring the sinonasal mucosa, compared to another topic medication.

PMID- 27888476
TI  - Histological detection of dynamic glial responses in the dysmyelinating Tabby
      jimpy mutant brain.
AB  - Oligodendrocytes (OLs) are glial cells that form myelin sheaths surrounding the
      axons in the central nervous system (CNS). Jimpy (jp) mutant mice are
      dysmyelinating disease models that show developmental abnormalities in myelinated
      OLs in the CNS. The causative gene in jp mice is the proteolipid protein (PLP)
      located on the X chromosome. Mutations in the jp allele result in exon 5 skipping
      and expression of abnormal PLP containing a C-terminal frame shift. Many lines of
      evidence suggest that abnormal PLP in OLs results in endoplasmic reticulum (ER)
      stress and cell death. To histologically detect glial responses in the jp mutant
      brain, we performed staining with lineage-specific markers. Using OL markers and
      OL progenitor cell marker staining, we identified reduced numbers of OL lineage
      cells in the jp mutant brain. Nuclear staining of the transcription factor Olig1
      was observed in the Tabby-jp brain, whereas cytoplasmic Olig1 staining was
      observed in the wild-type brain at postnatal day 21, suggesting that active
      myelination was present in the mutant brain. Many microglial cells with activated
      morphology and intensive staining of CD11b microglia marker were observed in the
      internal capsule of the mutant brain, a region of white matter containing
      residual OLs. Activated astrocytes with high glial fibrillary acidic protein
      immunoreactivity were also mainly observed in white matter. Finally, we performed
      in situ hybridization using C/EBP homologous protein (CHOP) antisense probes to
      detect ER stressed cells. CHOP mRNA was strongly expressed in residual OLs in the
      Tabby-jp mutant mice at postnatal stages. These data show that microglia and
      astrocytes exhibit dynamic glial activation in response to cell death of OLs
      during Tabby-jp pathogenesis, and that CHOP antisense probes may be a good marker
      for the detection of ER-stressed OLs in jp mutant mice.

PMID- 27888475
TI  - Assessing contamination of microalgal astaxanthin producer Haematococcus cultures
      with high-resolution melting curve analysis.
AB  - Due to its superior antioxidant capabilities and higher activity than other
      carotenoids, astaxanthin is used widely in the nutraceutical and medicine
      industries. The most prolific natural producer of astaxanthin is the unicellular
      green microalga Haematococcus pluvialis. The correct identification of any
      contaminants in H. pluvialis cultures is both essential and nontrivial for
      several reasons. Firstly, while it is possible to distinguish the main microalgal
      contaminant Coelastrella sp. (in H. pluvialis cultures), in practice, it is
      frequently a daunting and error-prone task for personnel without extensive
      experience in the microscopic identification of algal species. Secondly, the
      undetected contaminants may decrease or stop production of astaxanthin. Lastly,
      the presence of other contaminants such as fungi can eventually infect and
      destroy the whole algae collection. In this study, high-resolution melting (HRM)
      analysis was developed to detect microalgal and fungal contamination. The
      developed diagnostic procedure allowed to distinguish pure H. pluvialis samples
      from cultures contaminated with low amounts (1.25 ng/ml) of microalgal DNA and
      fungal DNA (2.5 ng/ml). Such discrimination is not possible with the use of
      microscopy observations and allows fast and efficient collection testing.

PMID- 27888477
TI  - Impact of Pediatric Acute Otitis Media on Child and Parental Quality of Life and
      Associated Productivity Loss in Malaysia: A Prospective Observational Study.
AB  - BACKGROUND: Acute otitis media (AOM) affects both child and parental quality of
      life (QoL). Data on QoL associated with AOM in Malaysia is sparse, and the burden
      of indirect costs have not been previously reported. OBJECTIVE: To determine the
      effect of pediatric AOM on child and parental QoL in Malaysia and its economic
      impact (indirect costs). METHODS: We utilized a set of QoL questionnaires (PAR
      AOM-QOL, OM-6, and EQ-5D) combined with questions addressing work/productivity
      loss and financial costs associated with caring for a child during his or her
      illness in an observational, multicenter, prospective study. RESULTS: One hundred
      and ten AOM patients aged <=5 years were included in the analysis. The majority
      of respondents were the patient's mother. Parental QoL was negatively affected
      for both emotional and daily disturbance scales, but the level of disturbance was
      low. Using OM-6, the greatest negative impact was on the child's QoL, followed by
      caregiver concerns, physical suffering, and emotional distress. Using EQ-5D, a
      moderately positive relationship between parents' emotional disturbance and daily
      disturbance, and a weak, negative correlation between parental emotional
      disturbance and parental health status was found. Parents with paid employment
      took an average of 21 h from work to care for their child, at an average cost of
      321.8 Malaysian ringgit (US$97) in addition to their contribution to direct
      medical costs. Productivity losses whilst at work, uncompensated wage losses, and
      leisure time losses are also reported. CONCLUSIONS: This study found that AOM is
      associated with some negative impact on parental QoL and significant economic
      impact at both patient and societal levels. The findings provide useful data on
      healthcare resource utilization and disease burden of AOM in Malaysia.

PMID- 27888478
TI  - Examining the Quality of Medicines at Kenyan Healthcare Facilities: A Validation
      of an Alternative Post-Market Surveillance Model That Uses Standardized Patients.
AB  - BACKGROUND: Promoting access to medicines requires concurrent efforts to
      strengthen quality assurance for sustained impact. Although problems of
      substandard and falsified medicines have been documented in low- and middle
      income countries, reliable information on quality is rarely available. OBJECTIVE:
      The aim of this study was to validate an alternative post-market surveillance
      model to complement existing models. METHODS: The study used standardized
      patients or mystery clients (people recruited from the local community and
      trained to pose as real patients) to collect medicine samples after presenting a
      pre-specified condition. The patients presented four standardized conditions to
      42 blinded facilities in Nairobi, Kenya, resulting in 166 patient-clinician
      interactions and dispensing of 300 medicines at facilities or nearby retail
      pharmacies. The medicine samples obtained thus resemble those that would be given
      to real patients. RESULTS: Sixty samples were selected from the 300, and sent for
      analysis at the Kenya National Quality Control Laboratory. Of these, ten (17%)
      did not comply with monograph specifications (three ibuprofen, two cetirizine,
      two amoxicillin/clavulanic acid combinations, and one each for prednisone,
      salbutamol and zinc). Five of the ten samples that failed had been
      inappropriately prescribed to patients who had presented symptoms of unstable
      angina. There was no association between medicine quality and ownership, size or
      location of the facilities. CONCLUSION: The study shows that the standardized
      patient model can provide insights into multiple dimensions of care, thus helping
      to link primary care encounters with medicine quality. Furthermore, it makes it
      possible to obtain medicines from blinded sellers, thus minimizing the risk of
      obtaining biased samples.

PMID- 27888479
TI  - Use of major ions to evaluate the hydrogeochemistry of groundwater influenced by
      reclamation and seawater intrusion, West Nile Delta, Egypt.
AB  - The aim of this research is to evaluate the groundwater geochemistry in western
      Nile Delta area as an example of an aquifer influenced by reclamation and
      seawater intrusion. To conduct this study, 63 groundwater samples and one surface
      water sample from El Nubaria Canal were collected. To estimate the origin of
      dissolved ions and the geochemical processes influencing this groundwater,
      integration between land use change, pedological, hydrogeological,
      hydrogeochemical, and statistical approaches was considered. Results suggest that
      the groundwater flow regime changed from northeast and southwest directions
      around El Nubaria canal before 1966 to northern and northeastern directions due
      to newly constructed channel network. Soil salinity and mineral contents, seepage
      from irrigation canal, and seawater intrusion are the main factors controlling
      the groundwater chemistry. Statistically, the groundwater samples were classified
      into eight groups, one to four for the deep groundwater and five to eight for the
      shallow groundwater. The deep groundwater is characterized by two groups of
      chemicals (SO4-HCO3-Mg-Ca-K and Cl-Na), while the shallow groundwater groups of
      chemicals are Na-Cl-SO4 and K-HCO3-Ca-Mg. Both shallow groundwater and deep
      groundwater are mostly saturated with respect to carbonate minerals and
      undersaturated with respect to chloride minerals. Sulfate minerals are above the
      saturation limit in the shallow groundwater, but in the deep samples, these
      minerals are under the saturation limit. Ion exchange, carbonate production,
      mineral precipitation, and seawater intrusion are the geochemical processes
      governing the groundwater chemistry in the study area.

PMID- 27888480
TI  - Serum concentrations of polychlorinated biphenyls (PCBs) in a Lebanese
      population: ENASB study.
AB  - Polychlorinated biphenyls (PCBs) are persistent organic pollutants that are still
      routinely detected 30 years after their restriction in many countries. PCBs have
      been associated with several non-communicable diseases. They are best measured
      via human biomonitoring (HBM). The concentrations of six indicator PCBs (PCBs 28,
      52, 101, 138, 153, and 180) were measured in the serum samples of 316 Lebanese
      students and employees from Saint Joseph University of Beirut, Lebanon, using gas
      chromatography coupled to an iron trap mass spectrometer detector. PCBs were
      detected in 56.3 to 59.2% of the serum samples. The sum of PCB (?PCBs) levels
      ranged from <LOD to 338.84 ng/g lipids, with a geometric mean level of 10.34 +/-
      0.98 ng/g lipids. The major contributor to the ?PCBs was PCB 180. In the present
      study, the levels were, in general, lower than the values observed in several
      Western and European countries. No association was found between age and
      concentration of any of the PCBs. In terms of risk for health, the highest levels
      were lower than critical limits such as HBM I and II values. We observed an
      inverted U-shaped association between levels of serum PCBs and the risk of
      overweight/obesity (OR = 2.140; CI = 1.095-4.185; p = 0.026). Regarding potential
      food contributors, we found no relation between PCB levels and fish consumption
      and a moderate relation with dairy product consumption (moderate consumers of
      dairy products had higher PCB levels compared to lower consumers) (16.92 +/-
      0.1/6.92 +/- 0.12; p = 0.025). The present study is the first to provide
      information regarding PCB levels in a Lebanese population. Larger studies are
      required in order to estimate the PCB exposure parameters of the Lebanese
      population.

PMID- 27888481
TI  - Rapid bacteria identification from environmental mining samples using MALDI-TOF
      MS analysis.
AB  - Copper mining has polluted soils and water, causing a reduction of the microbial
      diversity and a change in the structure of the resident bacterial communities. In
      this work, selective isolation combined with MALDI-TOF MS and the 16S rDNA method
      were used for characterizing cultivable bacterial communities from copper mining
      samples. The results revealed that MALDI-TOF MS analysis can be considered a
      reliable and fast tool for identifying copper-resistant bacteria from
      environmental samples at the genera level. Even though some results were
      ambiguous, accuracy can be improved by enhancing reference databases. Therefore,
      mass spectra analysis provides a reliable method to facilitate monitoring of the
      microbiota from copper-polluted sites. The understanding of the microbial
      community diversity in copper-contaminated sites can be helpful to understand the
      impact of the metal on the microbiome and to design bioremediation processes.

PMID- 27888483
TI  - Modeling the key factors that could influence the diffusion of CO2 from a
      wellbore blowout in the Ordos Basin, China.
AB  - Carbon dioxide (CO2) blowout from a wellbore is regarded as a potential
      environment risk of a CO2 capture and storage (CCS) project. In this paper, an
      assumed blowout of a wellbore was examined for China's Shenhua CCS demonstration
      project. The significant factors that influenced the diffusion of CO2 were
      identified by using a response surface method with the Box-Behnken experiment
      design. The numerical simulations showed that the mass emission rate of CO2 from
      the source and the ambient wind speed have significant influence on the area of
      interest (the area of high CO2 concentration above 30,000 ppm). There is a strong
      positive correlation between the mass emission rate and the area of interest, but
      there is a strong negative correlation between the ambient wind speed and the
      area of interest. Several other variables have very little influence on the area
      of interest, e.g., the temperature of CO2, ambient temperature, relative
      humidity, and stability class values. Due to the weather conditions at the
      Shenhua CCS demonstration site at the time of the modeled CO2 blowout, the
      largest diffusion distance of CO2 in the downwind direction did not exceed 200 m
      along the centerline. When the ambient wind speed is in the range of 0.1-2.0 m/s
      and the mass emission rate is in the range of 60-120 kg/s, the range of the
      diffusion of CO2 is at the most dangerous level (i.e., almost all Grade Four
      marks in the risk matrix). Therefore, if the injection of CO2 takes place in a
      region that has relatively low perennial wind speed, special attention should be
      paid to the formulation of pre-planned, emergency measures in case there is a
      leakage accident. The proposed risk matrix that classifies and grades blowout
      risks can be used as a reference for the development of appropriate regulations.
      This work may offer some indicators in developing risk profiles and emergency
      responses for CO2 blowouts.

PMID- 27888482
TI  - Biofertilizers: a potential approach for sustainable agriculture development.
AB  - The worldwide increase in human population raises a big threat to the food
      security of each people as the land for agriculture is limited and even getting
      reduced with time. Therefore, it is essential that agricultural productivity
      should be enhanced significantly within the next few decades to meet the large
      demand of food by emerging population. Not to mention, too much dependence on
      chemical fertilizers for more crop productions inevitably damages both
      environmental ecology and human health with great severity. Exploitation of
      microbes as biofertilizers is considered to some extent an alternative to
      chemical fertilizers in agricultural sector due to their extensive potentiality
      in enhancing crop production and food safety. It has been observed that some
      microorganisms including plant growth promoting bacteria, fungi, Cyanobacteria,
      etc. have showed biofertilizer-like activities in the agricultural sector.
      Extensive works on biofertilizers have revealed their capability of providing
      required nutrients to the crop in sufficient amounts that resulted in the
      enhancement of crop yield. The present review elucidates various mechanisms that
      have been exerted by biofertilizers in order to promote plant growth and also
      provides protection against different plant pathogens. The aim of this review is
      to discuss the important roles and applications of biofertilizers in different
      sectors including agriculture, bioremediation, and ecology.

PMID- 27888484
TI  - Persulfate-assisted photodegradation of diethylstilbestrol using monoclinic BiVO4
      under visible-light irradiation.
AB  - In this study, the photosynergistic performance of BiVO4 with persulfate (PS) is
      demonstrated under visible light irradiation for the first time.
      Diethylstilbestrol (DES) was selected as a reluctant compound, and factors
      including dosages of PS and catalyst, solution pHs, initial concertration of DES,
      and inorganic anions were evaluated. The morphology and chemical state of bismuth
      vanadate (BiVO4) was characterized by X-ray diffraction (XRD), scanning electron
      microscopy (SEM), energy-dispersive spectrometer (EDS), and ultraviolet-visible
      (UV-Vis) diffuse reflectance spectroscopy (DRS). It was found that the
      degradation of DES was promoted in either acid or alkaline solutions. The
      increase of PS and BiVO4 dosages was beneficial to the reactions, while
      incremental concentration of DES showed the inhibiting effect. By scavenging
      hVB+, Cl- was able to make the promotion, differentiated from the exsiting HCO-
      3. Moreover, the photocatalytic mechanism for the BiVO4/PS/vis-light system was
      proposed by using several probe compounds (isopropanol, tert-butanol, and 1,4
      benzoquinone), which consists of h+ VB/e- CB generation and recombination on the
      surface of BiVO4 as well as free radical oxidation in the solutions. The study
      provides a distinctive method to treat organic contaminants using visible light
      in the aqueous environment.

PMID- 27888485
TI  - Rapid in situ toxicity testing with luminescent bacteria Photorhabdus luminescens
      and Vibrio fischeri adapted to a small portable luminometer.
AB  - The present study demonstrates development of a rapid testing protocol based on a
      small portable luminometer using flash kinetic assessment of bacterial
      bioluminescence. The laboratory comparisons based on six model organic toxicants
      and two metals showed significant correlations between responses of freshwater
      bacteria Photorhabdus luminescens and standard marine bacterial species Vibrio
      fisheri. While P. luminescens was less sensitive in standard arrangements, the
      responses of both organisms were comparable in the newly introduced portable
      luminometer setup. The applicability and reproducibility of the portable
      luminometer protocol was further demonstrated in the assessment of 43 European
      wastewater effluents that were simultaneously tested for toxicity and analysed
      for 150 organic and 20 inorganic contaminants grouped into 13 major chemical
      classes. Clear association between the toxic responses in both compared bacterial
      species and the elevated levels of inorganic compounds (toxic metals),
      chlorophenols and benzotriazole anticorrosives was observed. The new protocol
      with a portable luminometer provides a fast (30 s) response and may be used as a
      tool for rapid in situ toxicity evaluation of freshwater environmental samples
      such as effluents.

PMID- 27888486
TI  - A Slowly Growing Orange Patch on the Cheek: Diagnosis of Lupus Vulgaris 20 Years
      After Onset of First Skin Changes.
AB  - Tuberculosis is a worldwide occurring disease that affects approximately 20-40%
      of the world's population and in particular in developing countries. However, in
      times of migration, industrialised countries are again being more and more
      affected. Cutaneous tuberculosis is rare and lupus vulgaris represents its most
      common form. Preferentially, young adults in developing or low-income countries
      are affected from cutaneous tuberculosis, which usually occurs in previously
      sensitized persons with a high degree of tuberculin sensitivity and a good
      immunoresponse. In Europe, more elderly people are involved. We present a case of
      lupus vulgaris that was diagnosed with a delay of about 20 years after onset of
      first skin changes.

PMID- 27888488
TI  - Phaeochromocytoma and Paraganglioma.
AB  - Phaeochromocytomas and paragangliomas are relatively uncommon tumours which may
      be manifest in many ways, specifically as sustained or paroxysmal hypertension,
      episodes of palpitations, sweating, headache and anxiety, or increasingly as an
      incidental finding. Recent studies have shown that an increasing number are due
      to germline mutations. This review concentrates on the diagnosis, biochemistry
      and treatment of these fascinating tumours.

PMID- 27888487
TI  - Mycotoxins as human carcinogens-the IARC Monographs classification.
AB  - Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins),
      mainly via food intake of plant and animal origin. The health risks stemming from
      mycotoxins may result from their toxicity, in particular their carcinogenicity.
      In order to prevent these risks, the International Agency for Research on Cancer
      (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the
      carcinogenic hazard assessment of some mycotoxins in humans, on the basis of
      epidemiological data, studies of cancer in experimental animals and mechanistic
      studies. The present article summarizes the carcinogenic hazard assessments of
      those mycotoxins, especially aflatoxins (aflatoxin B1, B2, G1, G2 and M1),
      fumonisins (fumonisin B1 and B2) and ochratoxin A (OTA). New information
      regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA
      in oxidative stress and the identification of epigenetic factors involved in OTA
      carcinogenesis-should they indeed provide strong evidence that OTA
      carcinogenicity is mediated by a mechanism that also operates in humans-could
      lead to the reclassification of OTA.

PMID- 27888489
TI  - The Role of DNA Methylation in Hypertension.
AB  - DNA methylation is the covalent modification of DNA that affects its function,
      without altering DNA sequences. Three important roles of DNA methylation include
      intrauterine programming, acquired predisposition, and transgenerational
      inheritance. A wide variety of factors can affect DNA methylation. Intrauterine
      programming involves drastic changes in DNA methylation patterns during cellular
      development and differentiation, which have a long-lasting effect on the
      predisposition of offspring. Influences from the mother, including maternal
      nutritional status, modify intrauterine epigenetic programming. In contrast to
      the rapid and drastic changes in utero, postnatal factors in daily life can also
      continue to slowly and dynamically change DNA methylation patterns in both
      somatic and germ cells. Epigenetic changes occurring in germ cell DNA exert a
      transgenerational impact on the phenotype of future generations, thus providing a
      means for ancestral transmission of environmental experiences. Despite adaptive
      ability, mismatch effect of transgenerational inheritance could be potentially
      harmful to health if environment has changed, and the acquired acclimatization is
      no longer beneficial. Increasing evidence from both human and animal studies
      indicates that DNA methylation exerts a causal impact on the development of
      hypertension. Therefore, an adverse outcome of maternal malnutrition could be the
      development of hypertension in offspring, whereby nutritional factors or disease
      conditions could induce phenotypes susceptible to hypertension through alteration
      of DNA methylation patterns. These factors are likely to alter DNA methylation
      patterns in all tissues including germ cells, and despite no direct evidence of
      an association between transgenerational epigenetic inheritance and hypertension,
      it is likely to play a role.

PMID- 27888490
TI  - Large-cell neuroendocrine carcinoma of the common bile duct: a case report and a
      review of literature.
AB  - BACKGROUND: Large-cell neuroendocrine carcinoma (LCNEC) of the bile duct is
      extremely rare and is a high-grade type of neuroendocrine tumor with an
      aggressive clinical course. Here, we report a case of LCNEC of the extrahepatic
      bile duct. CASE PRESENTATION: An 80-year-old man presented with severe jaundice.
      Endoscopic retrograde cholangiography and enhanced computed tomography revealed
      complete obstruction of the common bile duct (CBD) by a dense tumor measuring 1.5
      cm in diameter. Although there were no malignant cells in the biliary brush
      cytology, we suspected a cholangiocarcinoma and performed extrahepatic bile duct
      resection. Histologically, the LCNEC occupied most of the places deeper than the
      stratum submucosum and an adenocarcinoma component, approximately 15%, was
      present in the mucosa. There were no transitional areas between the two
      components. Immunohistochemically, the LCNEC cells were reactive for CD56 and
      synaptophysin and had a high MIB-1 index (72%). The patient died of multiple
      liver, lung, and peritoneal metastases 3 months after surgery. CONCLUSIONS: LCNEC
      of the CBD is particularly rare and has a very poor prognosis. Only five cases
      have been reported in the literature; therefore, there is no established
      effective therapy, including surgery, for LCNEC of the CBD at present. An
      accumulation of additional cases and further studies of multimodal treatment are
      required in the future to improve the prognosis.

PMID- 27888491
TI  - Twist removal of healed vs. nonhealed implants-a mechanical and histological
      study in mini pigs.
AB  - PURPOSE: The objective of this study was to evaluate the effect of removal torque
      (reverse torque) of titanium implants in peri-implant bone. METHODS: The P1-M1
      teeth were extracted bilaterally of 6 mini pigs (BR-1). Each animal received 6
      titanium implants, three for each side of mandible. On the right side of
      mandible, 3 implants reminded 9 months (9M) under masticatory activity and on the
      left side, other 3 implants were placed and immediately removed (IR). All 36
      implants were removed by removal torque, and the recorded values were
      statistically analyzed. Animals were euthanized right after the removal torque
      and recording. Each third (cervical, medium, and apical) of peri-implant bone was
      extracted and analyzed histological and immunohistochemically. Student's t test
      was used to determine statistical differences in the values between the 9M and IR
      samples. Data were presented as means with standard deviations. The level of
      significance was set at 5% (P < 0.05). RESULTS: Removal torque was higher in 9M
      experimental situation than in IR. Histological characteristics of mature bone
      were presented in the 9M experimental condition, and immature bone
      characteristics were presented in the IR experimental condition. Removal torque
      caused small fractures and rounding in the bone grooving. Immunohistochemical
      analysis reinforced the histological results; Student's t test provided
      statistically significant differences to osteocalcin expression in 9M samples and
      no statistically significant differences expression to collagen I in both
      experimental conditions (P < 0.05). CONCLUSIONS: Removal torque caused
      microscopical fractures and smoothing in the peri-implant bone grooves, but it
      does not compromise the bone healing.

PMID- 27888493
TI  - "The Penitent Magdalene": Jusepe de Ribera (1591-1652).
AB  - Jusepe or Jose de Ribera (1591-1652), known as Lo Spagnoletto ("the Little
      Spaniard"), has been a leading painter of the Spanish Baroque movement. In one of
      the portraits, de Ribera represented a scene in which the Magdalene shows a
      swelling at the base of the neck suggestive of a thyroid nodule.

PMID- 27888494
TI  - Patient-specific computer modelling - its role in the planning of transcatheter
      aortic valve implantation.
AB  - Transcatheter aortic valve implantation is increasingly used to treat patients
      with severe aortic stenosis who are at increased risk for surgical aortic valve
      replacement and is projected to be the preferred treatment modality. As patient
      selection and operator experience have improved, it is hypothesised that device
      host interactions will play a more dominant role in outcome. This, in combination
      with the increasing number of valve types and sizes, confronts the physician with
      the dilemma to choose the valve that best fits the individual patient. This
      necessitates the availability of pre-procedural computer simulation that is based
      upon the integration of the patient-specific anatomy, the physical and
      (bio)mechanical properties of the valve and recipient anatomy derived from in
      vitro experiments. The objective of this paper is to present such a model and
      illustrate its potential clinical utility via a few case studies.

PMID- 27888492
TI  - Vitamin D deficiency in early implant failure: two case reports.
AB  - An association between vitamin D deficiency and early dental implant failure is
      not properly verified, but its role in osteoimmunology is discussed. This article
      illustrates two case reports with vitamin D deficiency and early implant failure.
      Prior to implant placement, the first patient received crestal bone grafting with
      autologous material. Both patients received dental implants from different
      manufacturers in the molar region of the mandible. In the case of bone grafting
      in the first patient, all implants were placed in a two-stage procedure. All
      implants had to be removed within 15 days after implant placement. Vitamin D
      serum levels were measured: Both patients showed a vitamin D deficiency (serum
      vitamin D level <20 MUg/l). After vitamin D supplementation, implant placement
      was successful in both patients. Prospective, randomized clinical trials must
      follow to affirm the relationship between vitamin D deficiency, osteoimmunology,
      and early implant failure.

PMID- 27888496
TI  - Methanol Gas-Sensing Properties of SWCNT-MIP Composites.
AB  - The single-walled carbon nanotube (SWCNT)-molecularly imprinted powder (MIP)
      composites in this paper were prepared by mixing SWCNTs with MIPs. The structure
      and micrograph of the as-prepared SWCNTs-MIPs samples were characterized by XRD
      and TEM. The gas-sensing properties were tested through indirect-heating sensors
      based on SWCNT-MIP composites fabricating on an alumina tube with Au electrodes
      and Pt wires. The results showed that the structure of SWCNTs-MIPs is of
      orthogonal perovskite and the average particle size of the SWCNTs-MIPs was in the
      range of 10-30 nm. SWCNTs-MIPs exhibit good methanol gas-sensitive properties. At
      90  degrees C, the response to 1 ppm methanol is 19.7, and the response to the
      interferent is lower than 5 to the other interferent gases (ethanol,
      formaldehyde, toluene, acetone, ammonia, and gasoline). The response time and
      recovery time are 50 and 58 s, respectively. The as prepared SWCNTs-MIPs
      possesses good selectivity and high response to low concentrationmethanol.

PMID- 27888495
TI  - An unusual presentation of intraocular tuberculosis in a monocular patient:
      clinicopathological correlation.
AB  - BACKGROUND: Lack of uniform diagnostic criteria often poses a challenge in the
      diagnosis and management of tubercular uveitis. The index case describes an
      unusual presentation of tubercular panuveitis initially misdiagnosed as
      sympathetic ophthalmia, where the appropriate diagnosis was made using various
      imaging and laboratory investigations. RESULTS: A 52-year-old Indian woman
      underwent multimodal imaging, extensive clinical and laboratory work-up, and
      analysis of microbiological and histopathological specimens. At presentation, her
      best-corrected visual acuity (BCVA) was 20/30 in OD and no perception of light in
      OS. Ocular examination revealed multiple grayish-yellow choroiditis lesions
      resembling Dalen-Fuch's nodules, vitritis, and disc edema. Diagnosis of
      sympathetic ophthalmia was made and patient treated with intravenous and oral
      corticosteroids and immunosuppressive therapy. After an initial favorable
      response, the lesions progressively increased with worsening of vitritis. Due to
      worsening of chorioretinal lesions which were atypical for sympathetic
      ophthalmia, further investigations were performed that revealed positive
      tuberculin skin test and contrast-enhanced computerized tomography chest showed
      calcified mediastinal lymph nodes. Enucleation of OS confirmed acid-fast bacilli
      on Ziehl-Neelsen staining, tubercular granulomas on histopathology, and positive
      polymerase chain reaction. Anti-tubercular therapy and oral steroids were started
      with good healing response. CONCLUSIONS: Tubercular uveitis may have protean
      clinical manifestations. Thorough clinical evaluation and
      molecular/histopathological evaluation helps in establishing the diagnosis and
      the institution of appropriate therapy.

PMID- 27888497
TI  - Gold Nanoparticle-Quantum Dot Fluorescent Nanohybrid: Application for Localized
      Surface Plasmon Resonance-induced Molecular Beacon Ultrasensitive DNA Detection.
AB  - In biosensor design, localized surface plasmon resonance (LSPR)-induced signal
      from gold nanoparticle (AuNP)-conjugated reporter can produce highly sensitive
      nanohybrid systems. In order to retain the physicochemical properties of AuNPs
      upon conjugation, high colloidal stability in aqueous solution is needed. In this
      work, the colloidal stability with respect to the zeta potential (ZP) of four
      negatively charged thiol-functionalized AuNPs, thioglycolic (TGA)-AuNPs, 3
      mercaptopropionic acid (MPA)-AuNPs, L-cysteine-AuNPs and L-glutathione (GSH)
      AuNPs, and a cationic cyteamine-capped AuNPs was studied at various pHs, ionic
      strength, and NP concentration. A strong dependence of the ZP charge on the
      nanoparticle (NP) concentration was observed. High colloidal stability was
      exhibited between pH 3 and 9 for the negatively charged AuNPs and between pH 3
      and 7 for the cationic AuNPs. With respect to the ionic strength, high colloidal
      stability was exhibited at <=104 MUM for TGA-AuNPs, L-cysteine-AuNPs, and GSH
      AuNPs, whereas <=103 MUM is recommended for MPA-AuNPs. For the cationic AuNPs,
      very low ionic strength of <=10 MUM is recommended due to deprotonation at higher
      concentration. GSH-AuNPs were thereafter bonded to SiO2-functionalized alloyed
      CdZnSeS/ZnSe1.0S1.3 quantum dots (SiO2-Qdots) to form a plasmon-enhanced AuNP
      SiO2-Qdots fluorescent nanohybrid. The AuNP-SiO2-Qdots conjugate was afterward
      conjugated to a molecular beacon (MB), thus forming an ultrasensitive LSPR
      induced SiO2-Qdots-MB biosensor probe that detected a perfect nucleotide DNA
      sequence at a concentration as low as 10 fg/mL. The limit of detection was ~11
      fg/mL (1.4 fM) while the biosensor probe efficiently distinguished between single
      base mismatch and noncomplementary sequence target.

PMID- 27888498
TI  - Chitosan Nanolayered Cisplatin-Loaded Lipid Nanoparticles for Enhanced Anticancer
      Efficacy in Cervical Cancer.
AB  - In this study, cisplatin (CDDP)-loaded chitosan-coated solid lipid nanoparticles
      (SLN) was successfully formulated to treat HeLa cervical carcinoma. The
      formulation nanoparticles were nanosized and exhibited a controlled release of
      drug in physiological conditions. The blank nanoparticles exhibited an excellent
      biocompatibility profile indicating its suitability for cancer targeting. The
      incorporation of CDDP in SLN remarkably increased the cancer cell death as
      evident from the MTT assay. Importantly, CDDP-loaded chitosan-coated SLN (CChSLN)
      significantly (P < 0.05) decreased the viability of cancer cells even at low
      concentration. The higher cytotoxicity potential of CChSLN was attributed to the
      higher cellular uptake as well as the sustained drug release manner in comparison
      with CSLN. Consistent with the cytotoxicity assay, CChSLN showed the lowest IC50
      value of 0.6125 MUg/ml while CSLN presented 1.156 MUg/ml. CChSLN showed a
      significantly higher apoptosis in cancer cells compared to that of CSLN and CDDP,
      which is attributed to the better internalization of nanocarriers and controlled
      release of anticancer drugs in the intracellular environment. Our findings
      suggest that this new formulation could be a promising alternative for the
      treatment of cervical cancers. These findings are encouraging us to continue our
      research, with a more extended investigation of cellular response in real time
      and in animal models.

PMID- 27888499
TI  - Structural and electronic properties of two-dimensional stanene and graphene
      heterostructure.
AB  - Structural and electronic properties of two-dimensional stanene and graphene
      heterostructure (Sn/G) are studied by using first-principles calculations.
      Various supercell models are constructed in order to reduce the strain induced by
      the lattice mismatch. The results show that stanene interacts overall weakly with
      graphene via van der Waals (vdW) interactions. Multiple phases of different
      crystalline orientation of stanene and graphene could coexist at room
      temperature. Moreover, interlayer interactions in stanene and graphene
      heterostructure can induce tunable band gaps at stanene's Dirac point, and weak p
      type and n-type doping of stanene and graphene, respectively, generating a small
      amount of electron transfer from stanene to graphene. Interestingly, for model
      [Formula: see text] , there emerges a band gap about 34 meV overall the band
      structure, indicating it shows semiconductor feature.

PMID- 27888500
TI  - The effect of isoflurane on 18F-FDG uptake in the rat brain: a fully conscious
      dynamic PET study using motion compensation.
AB  - BACKGROUND: In preclinical positron emission tomography (PET) studies an
      anaesthetic is used to ensure that the animal does not move during the scan.
      However, anaesthesia may have confounding effects on the drug or tracer kinetics
      under study, and the nature of these effects is usually not known. METHOD: We
      have implemented a protocol for tracking the rigid motion of the head of a fully
      conscious rat during a PET scan and performing a motion compensated list-mode
      reconstruction of the data. Using this technique we have conducted eight rat
      studies to investigate the effect of isoflurane on the uptake of 18F-FDG in the
      brain, by comparing conscious and unconscious scans. RESULTS: Our results
      indicate that isoflurane significantly decreases the whole brain uptake, as well
      as decreasing the relative regional FDG uptake in the cortex, diencephalon, and
      inferior colliculi, while increasing it in the vestibular nuclei. No
      statistically significant changes in FDG uptake were observed in the cerebellum
      and striata. CONCLUSION: The applied event-based motion compensation technique
      allowed for the investigation of the effect of isoflurane on FDG uptake in the
      rat brain using fully awake and unrestrained rats, scanned dynamically from the
      moment of injection. A significant effect of the anaesthesia was observed in
      various regions of the brain.

PMID- 27888501
TI  - Infective Endocarditis: How Do We Currently Interpret the Duke Minor Criterion
      "Predisposing Heart Condition" in Native Valves?
AB  - INTRODUCTION: The term "predisposing heart condition" is used as an indication of
      antimicrobial prophylaxis to prevent infective endocarditis (IE) and as a
      criterion for diagnosing IE according to modified Duke criteria. The purpose of
      this survey was to elaborate clinician's knowledge and opinion on relevant heart
      conditions as a Duke minor criterion for the diagnosis of IE. METHODS: A
      questionnaire was created that consisted of two knowledge and two opinion
      questions on the term predisposing heart condition. The survey included results
      from 318 questionnaires with responses from specialists in the field of internal
      medicine, infectious diseases, and cardiology. RESULTS: The answers of what
      participants believed to be currently a Duke minor criterion and what they
      thought should be minor criterion were very distributed with a median accordance
      of 33%. CONCLUSION: The survey indicates that there is significant uncertainty
      regarding what is encountered as a Duke minor criterion predisposing heart
      condition in a native valve.

PMID- 27888502
TI  - A novel c132-134del mutation in Unverricht-Lundborg disease and the review of
      literature of heterozygous compound patients.
AB  - Unverricht-Lundborg disease or progressive myoclonic epilepsy type 1 (EPM1) is an
      autosomal recessive disease caused by mutation of the cystatin B gene (CSTB),
      located on chromosome 21q22.3. The most common mutation is an expansion of
      unstable dodecamer repetition (CCCCGCCCCGCG), whereas other types of mutations
      are rare. Among these, heterozygous compound mutations are described to induce a
      more severe phenotype than that of homozygous dodecameric repetition. We report
      two siblings affected by heterozygous compound mutations carrying a novel
      mutation of the deletion of three nucleotides in exon 2 of the gene in position
      132-134 of the coding sequence (c.132-134del) in the allele not including the
      dodecamer repetition. This mutation results in the loss of two amino acid
      residues and insertion of an asparagine in position 44 (p.Lys44_Ser45delinsAsn).
      Our patients presented a very different clinical picture. The male patient had a
      severe myoclonus, drug-resistant epilepsy and psychiatric comorbidity, while his
      affected sister had only very rare seizures and sporadic myoclonic jerks at
      awakening. The revision of literature about heterozygous compound EPM1 patients
      confirms this gender phenotypic expressivity, with female patients carrying less
      severe symptoms than male patients. These data lead to the hypothesis of complex
      gender-specific factors interacting with CSTB expressivity in EPM1 patients.

PMID- 27888504
TI  - Condensin Regulation of Genome Architecture.
AB  - Condensin complexes exist across all domains of life and are central to the
      structure and organization of chromatin. As architectural proteins, condensins
      control chromatin compaction during interphase and mitosis. Condensin activity
      has been well studied in mitosis but have recently emerged as important
      regulators of genome organization and gene expression during interphase. Here, we
      focus our discussion on recent findings on the molecular mechanism and how
      condensins are used to shape chromosomes during interphase. These findings
      suggest condensin activity during interphase is required for proper chromosome
      organization. J. Cell. Physiol. 232: 1617-1625, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27888503
TI  - Anti-hypercholesterolemic influence of the spice cardamom (Elettaria cardamomum)
      in experimental rats.
AB  - BACKGROUND: Cardamom (Elettaria cardamomum) is an aromatic seed spice grown
      extensively in India and used as a flavoring in sweets. In this study, the anti
      hypercholesterolemic effect of cardamom was evaluated in Wistar rats by inducing
      hypercholesterolemia with a high-cholesterol diet for 8 weeks. Dietary
      interventions were made with (a) cardamom powder (50 g kg-1 ), (b) cardamom oil
      (3 g kg-1 , equivalent to 50 g kg-1 cardamom) and (c) de-oiled cardamom powder
      (50 g kg-1 ). RESULTS: A significant reduction in blood total cholesterol (31%)
      and low-density lipoprotein cholesterol (44%) was observed by oral administration
      of cardamom oil in hypercholesterolemic rats, accompanied by a marked decrease in
      serum triglycerides by 42%. The cholesterol content of cardiac muscle was
      beneficially lowered by 39% with administration of cardamom oil in
      hypercholesterolemic rats. Liver triglycerides were reduced by 33%. Incorporation
      of cardamom oil/powder in the diet did not alter feed consumption by rats.
      Compromised activities of hepatic antioxidant enzymes in the hypercholesterolemic
      situation were generally countered by dietary cardamom. Treatment with de-oiled
      cardamom as well as cardamom oil countered the diminished activity of catalase in
      hypercholesterolemic animals. Cardamom also enhanced the activity of heart
      superoxide dismutase in the hypercholesterolemic situation. The concentration of
      ascorbic acid in serum was significantly increased by dietary cardamom or its
      fractions in the hypercholesterolemic situation. CONCLUSION: This animal study
      has established the potential of cardamom oil in restoring the alteration in
      lipid homeostasis in conditions of hypercholesterolemia. The significant
      reduction in atherogenicity index by dietary intervention with cardamom powder
      and cardamom oil indicates the potential cardioprotective effect of cardamom. (c)
      2016 Society of Chemical Industry.

PMID- 27888505
TI  - Geographical and ethnic distribution of MTHFR gene polymorphisms and their
      associations with diseases among Chinese population.
AB  - Numerous studies have investigated the distribution of methylenetetrahydrofolate
      reductase (MTHFR) C677T and A1298C polymorphisms and their associations with
      diseases in China. In this study we conducted a systematic review and meta
      analysis of these studies (715 eligible studies in total).Results revealed that
      the frequencies of the MTHFR C677T and A1298C polymorphisms varied markedly in
      different areas and ethnicities, and even showed geographical gradients. The
      MTHFR C677T polymorphism was significantly associated with 42 clinical disorders
      (p < 0.05), mostly relating to the diseases of circulatory system, birth defects
      and cancers. The association of the A1298C polymorphism with three diseases
      (coronary heart disease, breast cancer and neural tube defects fathers) was
      statistically significant (p < 0.05). However, according to the Venice criteria,
      only the associations of the C677T polymorphism with breast and ovarian cancers
      were assessed as having strong epidemiological credibility. This is the first
      study to provide a comprehensive assessment of the current status and gaps in
      genetic epidemiological study of the two polymorphisms in China, and its findings
      may be useful for medical and public health practices. Future studies are
      warranted to focus on the interactions of MTHFR genes with environmental exposure
      and with other genes, and to improve their methodological quality and reporting
      of findings.

PMID- 27888507
TI  - Understanding leisure preferences of young people with cerebral palsy.

PMID- 27888506
TI  - Rapid and safe response to low-dose carbamazepine in neonatal epilepsy.
AB  - OBJECTIVE: To evaluate treatment responses in benign familial neonatal epilepsy
      (BFNE). METHODS: We recruited patients with BFNE through a multicenter
      international collaboration and reviewed electroclinical and genetic details, and
      treatment response. All patients were tested at minimum for mutations/deletions
      in the KCNQ2, KCNQ3, and SCN2A genes. RESULTS: Nineteen patients were included in
      this study. A family history of neonatal seizures was positive in 16 patients,
      and one additional patient had a family history of infantile seizures. Mutations
      or deletions of KCNQ2 were found in 14, and of KCNQ3 in 2, of the 19 patients. In
      all patients, seizures began at 2-5 days of life and occurred multiple times per
      day. Four patients developed status epilepticus. Seizures were focal, alternating
      between hemispheres, and characterized by asymmetric tonic posturing associated
      with apnea and desaturation, followed by unilateral or bilateral asynchronous
      clonic jerking. Twelve of 19 patients were treated with multiple medications
      prior to seizure cessation. Seventeen of (88%) 19 patients were seizure-free
      within hours of receiving oral carbamazepine (CBZ) or oxcarbazepine (OXC).
      Earlier initiation of CBZ was associated with shorter hospitalization (p < 0.01).
      No side effects of CBZ were reported. All patients had normal development and
      remain seizure-free at a mean follow-up period of 7.8 years (6 months-16 years).
      SIGNIFICANCE: This study provides evidence that CBZ is safe and rapidly effective
      in neonates with BFNE, even in status epilepticus. We propose that CBZ should be
      the drug of choice in benign familial neonatal seizures.

PMID- 27888509
TI  - Functional properties of granule cells with hilar basal dendrites in the
      epileptic dentate gyrus.
AB  - OBJECTIVE: The maturation of adult-born granule cells and their functional
      integration into the network is thought to play a key role in the proper
      functioning of the dentate gyrus. In temporal lobe epilepsy, adult-born granule
      cells in the dentate gyrus develop abnormally and possess a hilar basal dendrite
      (HBD). Although morphological studies have shown that these HBDs have synapses,
      little is known about the functional properties of these HBDs or the intrinsic
      and network properties of the granule cells that possess these aberrant
      dendrites. METHODS: We performed patch-clamp recordings of granule cells within
      the granule cell layer "normotopic" from sham-control and status epilepticus (SE)
      animals. Normotopic granule cells from SE animals possessed an HBD (SE+ HBD+
      cells) or not (SE+ HBD- cells). Apical and basal dendrites were stimulated using
      multiphoton uncaging of glutamate. Two-photon Ca2+ imaging was used to measure
      Ca2+ transients associated with back-propagating action potentials (bAPs).
      RESULTS: Near-synchronous synaptic input integrated linearly in apical dendrites
      from sham-control animals and was not significantly different in apical dendrites
      of SE+ HBD- cells. The majority of HBDs integrated input linearly, similar to
      apical dendrites. However, 2 of 11 HBDs were capable of supralinear integration
      mediated by a dendritic spike. Furthermore, the bAP-evoked Ca2+ transients were
      relatively well maintained along HBDs, compared with apical dendrites. This
      further suggests an enhanced electrogenesis in HBDs. In addition, the output of
      granule cells from epileptic tissue was enhanced, with both SE+ HBD- and SE+ HBD+
      cells displaying increased high-frequency (>100 Hz) burst-firing. Finally, both
      SE+ HBD- and SE+ HBD+ cells received recurrent excitatory input that was capable
      of generating APs, especially in the absence of feedback inhibition.
      SIGNIFICANCE: Taken together, these data suggest that the enhanced excitability
      of HBDs combined with the altered intrinsic and network properties of granule
      cells collude to promote excitability and synchrony in the epileptic dentate
      gyrus.

PMID- 27888508
TI  - Outcomes following laryngectomy refusal after insufficient response to induction
      chemotherapy.
AB  - OBJECTIVE: To review patients who refused a total laryngectomy and were treated
      with radiotherapy (RT) after insufficient response to induction chemotherapy in a
      larynx preservation protocol for advanced-stage cancer of the larynx and to
      compare their outcomes with good responders. STUDY DESIGN: Retrospective cohort
      study. METHODS: Eighty-six patients treated with induction chemotherapy followed
      by RT were included in the analysis: 75 good responders and 11 insufficient
      responders who refused surgery. We compared overall survival (OS), disease-free
      survival (DFS), and laryngo-esophageal dysfunction-free survival (LEDFS) of the
      cohort populations in univariate and multivariate analyses. RESULTS: The median
      follow-up was 44 months. The 2-year and 5-year survival rates were respectively
      72.2% and 58.8% for OS, 62.8% and 49.4% for DFS, and 59.5% and 44.3% for LEDFS.
      No survival endpoint was significantly decreased among insufficient responders,
      contrary to what we expected. When we focused on patients with an initially fixed
      larynx, the recovery of larynx mobility after induction chemotherapy was not
      associated with OS (P = 0.6055), DFS (P = 0.459), or LEDFS (P = 0.7403).
      CONCLUSION: To the best of our knowledge, our study is the first patient
      treatment evaluation focused on subjects who refused a total laryngectomy after
      insufficient response to induction chemotherapy in a larynx preservation protocol
      for advanced-stage cancer of the larynx. Surprisingly, these patients treated
      with RT in our cancer center did not experience decreased functional and
      oncologic outcomes compared to good responders. Further studies will explore the
      relevance of response criteria and their evaluation methods. LEVEL OF EVIDENCE:
      4. Laryngoscope, 127:1791-1796, 2017.

PMID- 27888510
TI  - Tenosynovial giant cell tumors of the temporomandibular joint and lateral skull
      base: Review of 11 cases.
AB  - OBJECTIVES: To elucidate the clinical behavior, treatment, and outcomes of
      tenosynovial giant cell tumors (TGCT) involving the temporomandibular joint (TMJ)
      and adjacent temporal bone. STUDY DESIGN: Retrospective case series with
      histopathologic review. METHODS: A retrospective chart review was performed
      identifying and collecting data from all cases of TGCT involving the TMJ and
      adjacent temporal bone that were treated at the authors' center between January
      1960 and December 2015. RESULTS: Eleven histopathologically confirmed cases met
      inclusion criteria. The median age at diagnosis was 49 years, eight patients were
      men, and the median follow-up was 116 months. Computed tomographic (CT) imaging
      revealed a lytic expansile mass centered on the TMJ. Magnetic resonance imaging
      (MRI) most commonly exhibited hypointense signal on precontrast T1- and T2
      weighted sequences and variable postcontrast enhancement. The median delay in
      diagnosis was 24 months, and the most common presenting symptoms were hearing
      loss and pain. All patients underwent surgical resection, eight receiving gross
      total removal, one receiving near total removal, and two patients from early in
      the series receiving subtotal resection with neoadjuvant or adjuvant radiation.
      Histopathological review of surgical specimens revealed chondroid metaplasia in
      seven tumors. Eight of nine cases receiving gross total or near total resection
      have no evidence of recurrence to date. CONCLUSIONS: TGCT of the TMJ and temporal
      bone are rare and locally aggressive tumors that commonly present with
      nonspecific symptoms. A careful review of CT and MRI followed by early biopsy is
      critical in establishing an accurate diagnosis and facilitating appropriate
      treatment. TGCT of the TMJ more commonly contain chondroid metaplasia when
      compared to TGCT at other anatomic locations. Gross total resection is achievable
      in most cases and offers long-term cure. Radiation may be considered for
      recurrent disease or adjuvant therapy following subtotal resection. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 127:2340-2346, 2017.

PMID- 27888511
TI  - Dermatological content of U.K. undergraduate curricula: where are we now?

PMID- 27888512
TI  - Response to Astley's Letter to the Editor.

PMID- 27888513
TI  - Decreased allopregnanolone levels in cerebrospinal fluid obtained during status
      epilepticus.
AB  - Neuroactive steroids are increasingly considered as relevant modulators of
      neuronal activity. Especially allopregnanolone (AP) and pregnenolone sulfate (PS)
      have been shown to possess, respectively, anticonvulsant or proconvulsant
      properties. In view of the potential role of these steroids, we aimed at
      evaluating AP and PS levels in cerebrospinal fluid (CSF) and blood samples
      obtained from patients with status epilepticus (SE). To this purpose, we enrolled
      41 patients affected by SE and 41 subjects investigated for nonepileptic
      neurologic disorders. Liquid chromatographic procedures coupled with electrospray
      tandem mass spectrometry and routine laboratory investigations were performed.
      Significantly lower AP levels were found in the CSF of patients affected by SE (
      30%; p < 0.05, Mann-Whitney test). Notably, AP was not detectable in 28 of 41
      patients affected by SE (p < 0.01 vs. controls, Fisher's exact test). In serum,
      AP levels did not differ in the two considered groups. Conversely, PS was present
      at similar levels in the investigated groups. Finally, differences in AP levels
      could not be explained by a variation in CSF albumin content. These findings
      indicate that AP is defective in the CSF of patients affected by SE. This
      phenomenon was not dependent on carriers for steroids, such as albumin.

PMID- 27888514
TI  - The burden of premature mortality of epilepsy in high-income countries: A
      systematic review from the Mortality Task Force of the International League
      Against Epilepsy.
AB  - Since previous reviews of epidemiologic studies of premature mortality among
      people with epilepsy were completed several years ago, a large body of new
      evidence about this subject has been published. We aim to update prior reviews of
      mortality in epilepsy and to reevaluate and quantify the risks, potential risk
      factors, and causes of these deaths. We systematically searched the Medline and
      Embase databases to identify published reports describing mortality risks in
      cohorts and populations of people with epilepsy. We reviewed relevant reports and
      applied criteria to identify those studies likely to accurately quantify these
      risks in representative populations. From these we extracted and summarized the
      reported data. All population-based studies reported an increased risk of
      premature mortality among people with epilepsy compared to general populations.
      Standard mortality ratios are especially high among people with epilepsy aged <50
      years, among those whose epilepsy is categorized as structural/metabolic, those
      whose seizures do not fully remit under treatment, and those with convulsive
      seizures. Among deaths directly attributable to epilepsy or seizures, important
      immediate causes include sudden unexpected death in epilepsy (SUDEP), status
      epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature
      mortality imposes a significant public health burden, and many of the specific
      causes of death are potentially preventable. These require increased attention
      from healthcare providers, researchers, and public health professionals.

PMID- 27888515
TI  - Conserving the linear momentum in stochastic dynamics: Dissipative particle
      dynamics as a general strategy to achieve local thermostatization in molecular
      dynamics simulations.
AB  - Stochastic dynamics is a widely employed strategy to achieve local
      thermostatization in molecular dynamics simulation studies; however, it suffers
      from an inherent violation of momentum conservation. Although this short-coming
      has little impact on structural and short-time dynamic properties, it can be
      shown that dynamics in the long-time limit such as diffusion is strongly
      dependent on the respective thermostat setting. Application of the methodically
      similar dissipative particle dynamics (DPD) provides a simple, effective strategy
      to ensure the advantages of local, stochastic thermostatization while at the same
      time the linear momentum of the system remains conserved. In this work, the key
      parameters to employ the DPD thermostats in the framework of periodic boundary
      conditions are investigated, in particular the dependence of the system
      properties on the size of the DPD-region as well as the treatment of forces near
      the cutoff. Structural and dynamical data for light and heavy water as well as a
      Lennard-Jones fluid have been compared to simulations executed via stochastic
      dynamics as well as via use of the widely employed Nose-Hoover chain and
      Berendsen thermostats. It is demonstrated that a small size of the DPD region is
      sufficient to achieve local thermalization, while at the same time artifacts in
      the self-diffusion characteristic for stochastic dynamics are eliminated. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27888516
TI  - Beyond the two-group paradigm in studies of intergroup conflict and inequality:
      Third parties and intergroup alliances in xenophobic violence in South Africa.
AB  - Social psychologists typically conceptualize intergroup processes in terms of
      unequal pairs of social categories, such as an advantaged majority (e.g.,
      'Whites') and a disadvantaged minority (e.g., 'Blacks'). We argue that this two
      group paradigm may obscure the workings of intergroup power by overlooking: (1)
      the unique dynamics of intergroup relations involving three or more groups, and
      (2) the way some two-group relationships function as strategic alliances that
      derive meaning from their location within a wider relational context. We develop
      this argument through a field study conducted in a grape-farming town in South
      Africa in 2009, focusing on an episode of xenophobic violence in which a
      Zimbabwean farm worker community was forcibly evicted from their homes by their
      South African neighbours. Discursive analysis of interview accounts of the nature
      and origins of this violence shows how an ostensibly binary 'xenophobic' conflict
      between foreign and South African farm labourers was partially constituted
      through both groups' relationship with a third party who were neither victims nor
      perpetrators of the actual violence, namely White farmers. We highlight some
      potential political consequences of defaulting to a two-group paradigm in
      intergroup conflict studies.

PMID- 27888517
TI  - Differentiation of induced pluripotent stem cell-derived neutrophil granulocytes
      from common marmoset monkey (Callithrix jacchus).
AB  - BACKGROUND: Inherited and acquired marrow failure syndromes most commonly lead to
      defect in myeloid and/or neutrophil differentiation and/or function. Besides
      this, neutropenia induced by cancer-adjusted chemotherapy is a frequent clinical
      problem. In both cases, cell replacement therapy is a well-established, but due
      to necessity of donors limited and perilous procedure. Therefore, autologous cell
      replacement from patients' own marrow-derived cells lowers risk and bares new
      possibilities for therapy. Since the immune system of the marmoset monkey is
      known to show high similarity to humans, preclinical studies with these animals
      bare high hopes for immunologic research and cell replacement therapy. STUDY
      DESIGN AND METHODS: Marmoset-induced pluripotent stem (iPS) cells (cj-iPSC) were
      first cultivated on mouse embryonic feeder cells in medium containing recombinant
      human vascular endothelial growth factor. After 13 days, CD34+/vascular
      endothelial growth factor receptor-2 (VEGFR2)- cells were sorted, treated with
      interleukin (IL-3), thrombopoietin, and stem cell factor for 20 days and further
      cultivated with granulocyte-colony-stimulating factor (G-CSF) and IL-3 for 10
      days. RESULTS: CD34+/VEGFR2- cells could be generated in high amounts (39.65 +/-
      6.01%; 2.31 * 105 cells). Afterward, these hematopoietic progenitors could be
      successfully differentiated into mature cj-iPSC-derived neutrophils showing
      similar morphology, specific surface antigens, and neutrophil-specific gene
      products and in vitro phagocytic activity. CONCLUSION: cj-iPSC-derived
      neutrophils bare high hopes in hematologic cell replacement therapy. They exhibit
      high morphologic similarity to native neutrophils and present neutrophil-specific
      surface antigens, antimicrobial proteins, and gene products yielding an
      auspicious approach for continuative experiments including tests in living
      animals.

PMID- 27888518
TI  - A novel KEL silencing allele in a Brazilian patient with anti-Ku.

PMID- 27888519
TI  - Antibiotics in eosinophilic chronic rhinosinusitis: Rethinking maximal
      antimicrobial medical therapy.
AB  - OBJECTIVES/HYPOTHESIS: Eosinophilic chronic rhinosinusitis (eCRS) has recently
      been recognized as a CRS subtype characterized by inflammation rather than
      chronic infection. Consequently, the role of antibiotics as a component of
      maximal medical therapy for eCRS has been called into question. The purpose of
      this study was to investigate whether the use of antibiotics, which lack any
      secondary anti-inflammatory properties, are useful in the treatment of eCRS.
      STUDY DESIGN: Prospective individual cohort study. METHODS: Institutional review
      board-approved, prospective study of 39 patients presenting with chronic
      rhinosinusitis (CRS). In all patients, Lund-Kennedy endoscopy scores, Lund-Mackay
      computed tomography scores, and Sino-Nasal Outcome Test-22(SNOT-22) scores were
      obtained before and after treatment with amoxicillin-clavulanic acid twice a day
      (625 mg) for 4 weeks. Patients were subsequently stratified into eCRS and non
      eCRS groups based on having over 10 eosinophils per high-power field by
      histopathological examination. The efficacy of antibiotic therapy was compared
      between groups using the nonparametric Mann-Whitney U test. RESULTS: Within the
      non-eCRS group (n = 14), there was a significant improvement in both the Lund
      Mackay score (P = .002) and SNOT-22 score (P < .001) but not the endoscopy score.
      Among the eCRS patients (n = 25), the Lund-Mackay score was similarly improved (P
      = .007); however, there was no significant improvement in the endoscopy or SNOT
      22 scores. CONCLUSIONS: The use of antibiotics without independent anti
      inflammatory properties have limited efficacy in patients with eCRS. The concept
      of maximal medical therapy using antibiotics must continue to evolve in the
      setting of new evidence for inflammatory subtypes of CRS. LEVEL OF EVIDENCE: 2b.
      Laryngoscope, 127:794-796, 2017.

PMID- 27888520
TI  - Identifying the epileptogenic zone in interictal resting-state MEG source-space
      networks.
AB  - OBJECTIVE: In one third of patients, seizures remain after epilepsy surgery,
      meaning that improved preoperative evaluation methods are needed to identify the
      epileptogenic zone. A potential framework for such a method is network theory, as
      it can be applied to noninvasive recordings, even in the absence of epileptiform
      activity. Our aim was to identify the epileptogenic zone on the basis of hub
      status of local brain areas in interictal magnetoencephalography (MEG) networks.
      METHODS: Preoperative eyes-closed resting-state MEG recordings were
      retrospectively analyzed in 22 patients with refractory epilepsy, of whom 14 were
      seizure-free 1 year after surgery. Beamformer-based time series were
      reconstructed for 90 cortical and subcortical automated anatomic labeling (AAL)
      regions of interest (ROIs). Broadband functional connectivity was estimated using
      the phase lag index in artifact-free epochs without interictal epileptiform
      abnormalities. A minimum spanning tree was generated to represent the network,
      and the hub status of each ROI was calculated using betweenness centrality, which
      indicates the centrality of a node in a network. The correspondence of resection
      cavity to hub values was evaluated on four levels: resection cavity, lobar,
      hemisphere, and temporal versus extratemporal areas. RESULTS: Hubs were localized
      within the resection cavity in 8 of 14 seizure-free patients and in zero of 8
      patients who were not seizure-free (57% sensitivity, 100% specificity, 73%
      accuracy). Hubs were localized in the lobe of resection in 9 of 14 seizure-free
      patients and in zero of 8 patients who were not seizure-free (64% sensitivity,
      100% specificity, 77% accuracy). For the other two levels, the true negatives are
      unknown; hence, only sensitivity could be determined: hubs coincided with both
      the resection hemisphere and the resection location (temporal versus
      extratemporal) in 11 of 14 seizure-free patients (79% sensitivity). SIGNIFICANCE:
      Identifying hubs noninvasively before surgery is a valuable approach with the
      potential of indicating the epileptogenic zone in patients without interictal
      abnormalities.

PMID- 27888522
TI  - Barriers to the use of a federal travel grant by living kidney donors.
AB  - Living organ donation involves significant out-of-pocket costs, which burden
      donor candidates and may be an obstacle to donation. There is a single US grant
      (the National Living Donor Assistance Center-NLDAC) to cover live donor travel
      costs. Although there may be center-specific variability in grant utilization,
      prospective donors-and their intended recipients-must also meet eligibility
      criteria. In fact, the NLDAC grant is used by <10% of US live donors annually. We
      studied 154 consecutive kidney donor clinic evaluations (November 1, 2014-August
      30, 2015) to determine eligibility and usage patterns during the evaluation
      process. Of these, 63 (41%) were local, had travel benefits, or declined. Of the
      remaining 91 prospective donors who might have benefited from grant support, only
      29 (32%) obtained the grant. The other 62 (68%) did not meet eligibility
      screening. The major reason prospective donors were ineligible was that the
      recipient's household income was outside the required means test (ie, >300% of
      the federal poverty level) (n=51; 82%). The remaining exclusions (n=11; 18%)
      included being a nondirected donor, not meeting residency requirements, and
      "other." Expanding NLDAC eligibility criteria-by broadening the recipient means
      test or by taking steps to eliminate it from the NLDAC charter-would reduce
      financial burdens associated with live donation.

PMID- 27888521
TI  - Cancer-associated mesenchymal stroma fosters the stemness of osteosarcoma cells
      in response to intratumoral acidosis via NF-kappaB activation.
AB  - The role of mesenchymal stem cells (MSC) in osteosarcoma (OS), the most common
      primary tumor of bone, has not been extensively elucidated. We have recently
      shown that OS is characterized by interstitial acidosis, a microenvironmental
      condition that is similar to a wound setting, in which mesenchymal reactive cells
      are activated to release mitogenic and chemotactic factors. We therefore intended
      to test the hypothesis that, in OS, acid-activated MSC influence tumor cell
      behavior. Conditioned media or co-culture with normal MSC previously incubated
      with short-term acidosis (pH 6.8 for 10 hr, H+ -MSC) enhanced OS clonogenicity
      and invasion. This effect was mediated by NF-kappaB pathway activation. In fact,
      deep-sequencing analysis, confirmed by Real-Time PCR and ELISA, demonstrated that
      H+ -MSC differentially induced a tissue remodeling phenotype with increased
      expression of RelA, RelB and NF-kappaB1, and downstream, of CSF2/GM-CSF, CSF3/G
      CSF and BMP2 colony-promoting factors, and of chemokines (CCL5, CXCL5 and CXCL1),
      and cytokines (IL6 and IL8), with an increased expression of CXCR4. An increased
      expression of IL6 and IL8 were found only in normal stromal cells, but not in OS
      cells, and this was confirmed in tumor-associated stromal cells isolated from OS
      tissue. Finally, H+ -MSC conditioned medium differentially promoted OS stemness
      (sarcosphere number, stem-associated gene expression), and chemoresistance also
      via IL6 secretion. Our data support the hypothesis that the acidic OS
      microenvironment is a key factor for MSC activation, in turn promoting the
      secretion of paracrine factors that influence tumor behavior, a mechanism that
      holds the potential for future therapeutic interventions aimed to target OS.

PMID- 27888523
TI  - The cotton beta-galactosyltransferase 1 (GalT1) that galactosylates
      arabinogalactan proteins participates in controlling fiber development.
AB  - Arabinogalactan proteins (AGPs) are highly glycosylated proteins that play
      pivotal roles in diverse developmental processes in plants. Type-II AG glycans,
      mostly O-linked to the hydroxyproline residues of the protein backbone, account
      for up to 95% w/w of the AGP, but their functions are still largely unclear.
      Cotton fibers are extremely elongated single-cell trichomes on the seed
      epidermis; however, little is known of the molecular basis governing the
      regulation of fiber cell development. Here, we characterized the role of a CAZy
      glycosyltransferase 31 (GT31) family member, GhGalT1, in cotton fiber
      development. The fiber length of the transgenic cotton overexpressing GhGalT1 was
      shorter than that of the wild type, whereas in the GhGalT1-silenced lines there
      was a notable increase in fiber length compared with wild type. The carbohydrate
      moieties of AGPs were altered in fibers of GhGalT1 transgenic cotton. The
      galactose: arabinose ratio of AG glycans was higher in GhGalT1 overexpression
      fibers, but was lower in GhGalT1-silenced lines, compared with that in the wild
      type. Overexpression of GhGalT1 upregulates transcript levels of a broad range of
      cell wall-related genes, especially the fasciclin-like AGP (FLA) backbone genes.
      An enzyme activity assay demonstrated that GhGalT1 is a beta-1,3
      galactosyltransferase (beta-1,3-GalT) involved in biosynthesis of the beta-1,3
      galactan backbone of the type-II AG glycans of AGPs. We also show that GhGalT1
      can form homo- and heterodimers with other cotton GT31 family members to
      facilitate AG glycan assembly of AGPs. Thus, our data demonstrate that GhGalT1
      influences cotton fiber development via controlling the glycosylation of AGPs,
      especially FLAs.

PMID- 27888525
TI  - Breaking Sad: Unleashing the Breakthrough Potential of Ketamine's Rapid
      Antidepressant Effects.
AB  - Preclinical Research The surprising results of a small clinical trial on the
      effects of low dose ketamine, a 65-year old anesthetic drug that is also used off
      label for chronic pain and recreationally as a club drug, in eight depressed
      subjects unleashed the most significant advance in antidepressant drug
      development in decades. That study and subsequent ones have demonstrated that low
      dose, infused ketamine is able to induce a remission of depression in patients
      who have failed conventional medications, within 24 h. The apparent increased
      efficacy and rapid onset of effect of ketamine distinguish it from all other
      current antidepressant treatments. However, a single infusion of subanesthetic
      doses of ketamine produces benefits that typically last <3 weeks. The infusions
      are associated with a transient "psychedelic" experience and increased blood
      pressure that requires monitoring. There is also a theoretical potential to
      induce ketamine addiction. These features limit ketamine's ability to be a widely
      used treatment for depression and thus limit is ability to have a meaningful
      impact on the heavy morbidity and mortality associated with this disorder,
      despite its "breakthrough" rate of efficacy and speed of action. While growing
      numbers of clinicians are using ketamine to treat treatment resistant depression,
      many in the depression field believe that the aforementioned limiting aspects
      need to be separated from its remarkable therapeutic effects in order to unlock
      the breakthrough potential of this agent. To that end, drug development efforts
      have focused on various features of ketamine as targets for optimization
      including its modulation of the NMDA receptor, its pharmacokinetics, its
      chirality and its active metabolites including HNK (2R, 6R)-hyroxynorketamine.
      Drug Dev Res 77 : 489-494, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27888524
TI  - Systematic deletion of the ER lectin chaperone genes reveals their roles in
      vegetative growth and male gametophyte development in Arabidopsis.
AB  - Calnexin (CNX) and calreticulin (CRT) are homologous lectin chaperones in the
      endoplasmic reticulum (ER) that facilitate glycoprotein folding and retain
      folding intermediates to prevent their transit via the secretary pathway. The
      Arabidopsis genome has two CNX (CNX1 and CNX2) and three CRT (CRT1, CRT2 and
      CRT3) homologs. Despite growing evidence of the biological roles of CNXs and
      CRTs, little is understood about their function in Arabidopsis growth and
      development under normal conditions. Here, we report that the deletion of CNX1,
      but not of CNX2, in the crt1 crt2 crt3 triple mutation background had an adverse
      effect on pollen viability and pollen tube growth, leading to a significant
      reduction in fertility. The cnx1 crt1 crt2 crt3 quadruple mutation also conferred
      severe defects in growth and development, including a shortened primary root,
      increased root hair length and density, and reduced plant height. Disruption of
      all five members of the CNX/CRT family was revealed to be lethal. Finally, the
      abnormal phenotype of the cnx1 crt1 crt2 crt3 quadruple mutants was completely
      rescued by either the CNX1 or CNX2 cDNA under the control of the CNX1 promoter,
      suggesting functional redundancy between CNX1 and CNX2. Taken together, these
      results provide genetic evidence that CNX and CRT play essential and overlapping
      roles during vegetative growth and male gametophyte development in Arabidopsis.

PMID- 27888527
TI  - Electrophysiological correlates of decision making impairment in multiple
      sclerosis.
AB  - Although previous studies have shown that patients with multiple sclerosis (MS)
      may exhibit impaired decision making (DM), the specific neuro-cognitive processes
      that underlie this deficiency remain unknown. Inefficient DM may occur due to
      poor option assessment or a deficit in the evaluation of choice outcomes. This
      study uses, for the first time, the event-related potential (ERP) technique to
      analyze these DM subprocesses in patients with MS. Sixteen MS patients and
      nineteen control subjects performed a DM task based on the Iowa Gambling Task
      while a digital EEG was recorded. The P3b was analyzed as an index of option
      assessment, and both the feedback-related negativity (FRN) and P3b were
      considered markers for choice outcome evaluation. We found that MS patients made
      a larger number of unfavorable choices during the DM task (P = 0.02), with no
      differences between groups for reaction times. There were no significant
      differences in P3b for option assessment between the groups. In the control
      group, the type of feedback (gain, loss, or nothing) modified the FRN (F = 3.72,
      P = 0.033) and the P3b (F = 3.15, P = 0.059). This effect was not observed in the
      MS group. Also, FRN latencies were shorter in the MS group compared to controls
      (P = 0.047). Finally, lesions in temporal regions revealed by MRI were associated
      with DM both in behavioral and electrophysiological terms. We conclude that the
      DM impairment of patients with MS may be due to a deficit in their evaluation of
      choice outcomes or a general alteration in emotional reactivity.

PMID- 27888526
TI  - The optimal single-dose regimen of rasburicase for management of tumour lysis
      syndrome in children and adults: a systematic review and meta-analysis.
AB  - WHAT IS KNOWN AND OBJECTIVE: To perform a meta-analysis exploring the optimal
      single-dose regimen for managing tumour lysis syndrome (TLS) in children and
      adults with haematological malignancies. METHODS: We systematically searched
      PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov
      website for studies regarding single-dose rasburicase in paediatric and adult
      patients with TLS. Data were analysed using Open MetaAnalyst statistical
      software. RESULTS: Fifteen adult studies (fourteen retrospective studies and one
      randomized controlled trial) and four observational studies using children were
      extracted, with a total of 906 and 92 subjects, respectively. Single doses of
      1.5, 3, 4.5, 6, 7.5 mg and weight-based single doses of 0.05 and 0.15 mg/kg were
      compared. The response rate for 6, 7.5 mg and 0.15 mg/kg single doses was 90%
      (95% CI: 0.825-0.974), 98.6% (95% CI: 0.957-1.015) and 93.6% (95% CI: 0.864
      1.007), respectively, and higher than other dosing regimens tested. The single
      doses of 6 mg and 0.15 mg/kg rasburicase decreased uric acid levels more than the
      other regimens, and the mean uric acid reduction was 8.45 mg/dL (95% CI, 7.51
      9.38) and 10 mg/dL (95% CI, 8.58-11.42), respectively. WHAT IS NEW AND
      CONCLUSION: Our meta-analysis revealed that, for adult patients, a single 6 mg
      rasburicase dose is sufficient to normalize and sustain lower uric acid and
      creatinine levels in adults with TLS. This dose, therefore, balances cost and
      efficacy of treatment. The 3- and 4.5-mg single dose can be considered if the
      baseline uric acid level <12 mg/dL, with close monitoring of clinical and
      biochemical parameters, and repeat dosing if required. The 1.5 mg and 0.15 mg/kg
      single dose were sufficient to manage TLS in children.

PMID- 27888528
TI  - Hormone-Related Migraine Headaches and Mood Disorders: Treatment with Estrogen
      Stabilization.
AB  - Because estrogens and the trigeminal system are inherently linked, prescribers
      who are treating a woman with a hormonally related mood disorder and migraine
      headaches should consider hormonal options to optimize the patient's treatment.
      This article discusses the interrelationships of estrogen, serotonin, and the
      trigeminal system as they relate to menstrual migraine occurrence and hormone
      related mood symptoms. In addition, clinical examples are provided to facilitate
      the prescribers treating women during reproductive transitions in which declining
      estrogens are related to their suffering.

PMID- 27888530
TI  - Perturbation of longitudinal relaxation rate in rotating frame (PLRF) analysis
      for quantification of chemical exchange saturation transfer signal in a transient
      state.
AB  - PURPOSE: To develop a novel analytical method for quantification of chemical
      exchange saturation transfer (CEST) in the transient state. The proposed method
      aims to reduce the effects of non-chemical-exchange (non-CE) parameters on the
      CEST signal, emphasizing the effect of chemical exchange. METHODS: The difference
      in the longitudinal relaxation rate in the rotating frame ( DeltaR1rho) was
      calculated based on perturbation of the Z-value by R1rho, and a saturation-pulse
      amplitude-compensated exchange-dependent relaxation rate (SPACER) was determined
      with a high-exchange-rate approximation. In both phantom and human subject
      experiments, MTRasym (representative of the traditional CEST index), DeltaR1rho,
      and SPACER were measured, evaluated, and compared by altering the non-CE
      parameters in a transient-state continuous-wave CEST sequence. RESULTS: In line
      with the theoretical expectation, our experimental data demonstrate that the
      effects of the non-CE parameters can be more effectively reduced using the
      proposed indices (  DeltaR1rho and SPACER) than using the traditional CEST index
      ( MTRasym). CONCLUSION: The proposed method allows for the chemical exchange
      weight to be better emphasized in the transient-state CEST signal, which is
      beneficial, in practice, for quantifying the CEST signal. Magn Reson Med 78:1711
      1723, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine.

PMID- 27888529
TI  - Long-term progression of viral load and serum markers of fibrosis among treated
      and untreated patients with chronic hepatitis B.
AB  - BACKGROUND AND AIMS: Antiviral therapy for patients with hepatitis B (HBV)
      infection is generally deferred for "immune inactive" patients, although
      longitudinal changes in viral load and liver fibrosis remain understudied in this
      population. Likewise, in treated patients, the temporal relationship between
      changes in viral load and liver fibrosis is not well characterized. Using data
      from the chronic hepatitis cohort study, the study investigated viral load and
      the Fibrosis-4 index (FIB4, a serum-based marker of liver fibrosis) trajectories
      in both untreated and treated HBV patients. MATERIALS AND METHODS: We applied a
      bivariate, piecewise, linear spline, mixed-effects modeling approach to data from
      766 HBV patients (342 untreated, 424 treated). Treatment selection bias was
      adjusted using propensity scores. Multiple sensitivity analyses were used to
      confirm results in untreated patients. RESULTS: Among all untreated patients,
      FIB4 began to increase by 0.9% per month (11% per year; P < 0.05) at 28 months
      post-index date, suggesting fibrosis progression. Significant FIB4 progression
      was also observed in a subgroup analysis of "immune inactive" untreated patients.
      In treated patients, viral load declined 31.8% per month (P < 0.05) for the first
      5 months after treatment initiation, and 1.4-1.7% per month (P < 0.05)
      thereafter. At 5 months after treatment initiation, FIB4 began to decline 0.5%
      per month (P < 0.05), stabilizing at 28 months. CONCLUSION: Among untreated HBV
      patients, FIB4 gradually increases over time, suggesting fibrosis progression,
      even in those patients designated as immune inactive. In treated patients,
      antiviral therapy results in a rapid decline in viral load followed by a delayed
      decline in markers of liver fibrosis.

PMID- 27888532
TI  - Biliary strictures complicating liver transplantation in pediatric patients:
      Experience in a South American transplant center.
AB  - OBJECTIVE: To describe the experience of percutaneous transhepatic
      cholangiography (PTC) with biliary dilatation and drainage after pediatric liver
      transplantation and to determine the long-term outcome of this procedure.
      METHODS: Retrospective study from 2001 to 2013. Follow-up after treatment was
      also undertaken. A survival analysis was performed in patients in whom the
      procedure and eventual removal of the catheter were successful. RESULTS: In all,
      196 children received liver transplants; 40 of them (20 boys and 20 girls; median
      age of 4 years) were treated using PTC due to biliary complications. Sixty-one
      PTC procedures were performed in 40 liver transplant recipients. Technically
      successful PTC was achieved in 87.5% of the patients. The probability of a
      patient not developing unfavorable outcomes 1, 5, and 10 years after treatment
      was 88.9%, 83.0%, and 74.1%.

PMID- 27888533
TI  - Advances in understanding broad-spectrum resistance to pathogens in rice.
AB  - Rice diseases caused by multiple pathogen species are a major obstacle to
      achieving optimal yield. Using host pathogen species-non-specific broad-spectrum
      resistance (BSR) for rice improvement is an efficient way to control diseases.
      Recent advances in rice genomics and improved understanding of the mechanisms of
      rice-pathogen interactions have shown that using a single gene to improve rice
      BSR to multiple pathogen species is technically possible and the necessary
      resources exist. A variety of rice genes, including major disease resistance
      genes and defense-responsive genes, which function in pattern-triggered immunity
      signaling, effector-triggered immunity signaling or quantitative resistance, can
      mediate BSR to two or more pathogen species independently. These genes encode
      diverse proteins and function differently in promoting disease resistance, thus
      providing a relatively broad choice for different breeding programs. This updated
      knowledge will facilitate rice improvement with pathogen species-non-specific BSR
      via gene marker-assisted selection or biotechnological approaches.

PMID- 27888534
TI  - Early steroid withdrawal results in improved patient and graft survival and lower
      risk of post-transplant cardiovascular risk profiles: A single-center 10-year
      experience.
AB  - Long-term use of steroids results in predictable secondary effects that can lead
      to increased morbidity and mortality. In this study, we present 10 years worth of
      data of early steroid withdrawal (ESW) immunosuppression consisting of
      mycophenolate, sirolimus, and tacrolimus. From 2003 to 2013, 563 kidney
      transplant recipients were weaned off steroids prior to discharge. We compared
      outcomes with that of our 65 historical controls maintained on steroids. We
      analyzed graft and patient survival and determined the incidence of steroid
      related comorbidities such as hypertension, hypercholesterolemia, diabetes,
      coronary artery disease, and weight gain. Patients on ESW maintenance
      immunosuppression had improved patient and graft survival compared to controls.
      (HR: 0.23; P<=.011, 0.57; P=.026). Rates of biopsy-proven acute rejection were
      not different among both groups (HR: 1.24; P=.610). Incidence of post-transplant
      diabetes were reduced but not statistically significant (OR: 0.67; P=.138).
      Additionally, the development of hypertension (OR: 0.86, P<=.01),
      hypercholesterolemia (RR: 0.82; P=.027), CAD (RR: 0.43; P=.002), and >20 lbs.
      weight gain (RR: 0.29; P<=.01) was significantly improved over 10 years following
      initiation of ESW protocols. Early steroid withdrawal in renal transplant
      recipients results in improved patient and graft survival as well as better rates
      of post-transplant comorbid conditions.

PMID- 27888535
TI  - Chitin receptor CERK1 links salt stress and chitin-triggered innate immunity in
      Arabidopsis.
AB  - In nature, plants need to respond to multiple environmental stresses that require
      the involvement and fine-tuning of different stress signaling pathways. Cross
      tolerance, in which plants pre-treated with chitin (a fungal microbe-associated
      molecular pattern) have improved salt tolerance, was observed in Arabidopsis, but
      is not well understood. Here, we show a unique link between chitin and salt
      signaling mediated by the chitin receptor CHITIN ELICITOR RECEPTOR KINASE 1
      (CERK1). Transcriptome analysis revealed that salt stress-induced genes are
      highly correlated with chitin-induced genes, although this was not observed with
      other microbe-associated molecular patterns (MAMPs) or with other abiotic
      stresses. The cerk1 mutant was more susceptible to NaCl than was the wild type.
      cerk1 plants had an irregular increase of cytosolic calcium ([Ca2+ ]cyt ) after
      NaCl treatment. Bimolecular fluorescence complementation (BiFC) and co
      immunoprecipitation experiments indicated that CERK1 physically interacts with
      ANNEXIN 1 (ANN1), which was reported to form a calcium-permeable channel that
      contributes to the NaCl-induced [Ca2+ ]cyt signal. In turn, ann1 mutants showed
      elevated chitin-induced rapid responses. In short, molecular components
      previously shown to function in chitin or salt signaling physically interact and
      intimately link the downstream responses to fungal attack and salt stress.

PMID- 27888536
TI  - Ascorbate degradation in tomato leads to accumulation of oxalate, threonate and
      oxalyl threonate.
AB  - Ascorbate content in plants is controlled by its synthesis from carbohydrates,
      recycling of the oxidized forms and degradation. Of these pathways, ascorbate
      degradation is the least studied and represents a lack of knowledge that could
      impair improvement of ascorbate content in fruits and vegetables as degradation
      is non-reversible and leads to a depletion of the ascorbate pool. The present
      study revealed the nature of degradation products using [14 C]ascorbate labelling
      in tomato, a model plant for fleshy fruits; oxalate and threonate are accumulated
      in leaves, as is oxalyl threonate. Carboxypentonates coming from diketogulonate
      degradation were detected in relatively insoluble (cell wall-rich) leaf material.
      No [14 C]tartaric acid was found in tomato leaves. Ascorbate degradation was
      stimulated by darkness, and the degradation rate was evaluated at 63% of the
      ascorbate pool per day, a percentage that was constant and independent of the
      initial ascorbate or dehydroascorbic acid concentration over periods of 24 h or
      more. Furthermore, degradation could be partially affected by the ascorbate
      recycling pathway, as lines under-expressing monodehydroascorbate reductase
      showed a slight decrease in degradation product accumulation.

PMID- 27888537
TI  - Applying strong external electric field to thiophene-based oligomers: A promising
      approach to upgrade semiconducting performance.
AB  - A key parameter dictating the rate of charge transfer (CT) is reorganization
      energy (lambda), an energy associated with geometry changes during hole/electron
      transfer. We show that "ironing" the inter-ring dihedral angles of
      oligothiophenes via proper substitutions or insertions (e.g., -OR, -F or -C=C-),
      decreases the lambda and thus promotes CT according to Marcus equation. Our
      results demonstrate, to attain a smaller lambda, extending oligomer length is
      only significant if the flattened backbone structure is realized. Of great
      interest is that external electric fields, which are ubiquitous in electronic
      devices yet commonly overlooked in the computation of lambda, can have a
      significantly greater impact than conventional substitutions. It is important to
      emphasize, the responses of lambda to external fields is system-dependent.
      Compared to fused-ring conjugated systems, single-bond connected thiophenes are
      more sensitive to external fields. Fx lowers the lambda (552 meV) of
      quaterthiophene by almost 80% at the intensity of 1 V/A, down to a value (125
      meV) which is even lower than that of pentacene (154 meV) and rubrene (219 meV)
      at the same level of theory. (c) 2016 Wiley Periodicals, Inc.

PMID- 27888538
TI  - Specific N-glycan alterations are coupled in epithelial-mesenchymal transition
      induced by EGF in GE11 epithelial cells.
AB  - Epithelial-mesenchymal transition (EMT) is a phenomenon in cancer progression
      during which cancer cells undergo remarkable alteration acquiring highly invasive
      property. The aim of this study was to evaluate specific N-glycan alterations
      during EMT induced by epidermal growth factor (EGF) in GE11 epithelial cells.
      Herein, we demonstrated that EGF activated epidermal growth factor receptor
      (EGFR)/Akt/extracellular signal-regulated kinase (ERK) phosphorylation and
      promoted GE11 cell proliferation. Meanwhile, EGF stimulated the epithelial cells
      to undergo morphological alteration, destroying cell-cell inter-contact and
      exhibiting mesenchymal cells higher metastatic potential. A wound-healing assay
      showed the migratory ability increased 1.5-fold after EGF treatment. Moreover,
      the relative intensity of N-cadherin versus E-cadherin increased 2.6-fold, and
      the E-cadherin distribution in cell-cell junctions became jagged and faint after
      EGF incubation for 72 h. Interestingly, the amounts of bisecting GlcNAc structure
      were dramatically declined, by contrast, the formation of beta1,6 GlcNAc branches
      on cell surface was upregulated during EMT induced by EGF. To understand the
      roles of N-glycans in EGF-induced EMT, the cells were stably transfected with N
      acetylglucosaminyltransferase III (GnT-III), which catalyzes the bisecting GlcNAc
      structure formation. As the markers for EMT, EGF-induced E-cadherin decrease and
      fibronectin increase were delayed in GnT-III-overexpressing cells. Taken
      together, these results demonstrated that specific N-glycan alterations were
      coupled in EMT induced by EGF, which might be contributed to diagnosis and
      therapy of tumor metastasis.

PMID- 27888531
TI  - Fate of microglia during HIV-1 infection: From activation to senescence?
AB  - Microglia support productive human immunodeficiency virus type 1 (HIV-1)
      infection and disturbed microglial function could contribute to the development
      of HIV-associated neurocognitive disorders (HAND). Better understanding of how
      HIV-1 infection and viral protein exposure modulate microglial function during
      the course of infection could lead to the identification of novel therapeutic
      targets for both the eradication of HIV-1 reservoir and treatment of
      neurocognitive deficits. This review first describes microglial origins and
      function in the normal central nervous system (CNS), and the changes that occur
      during aging. We then critically discuss how HIV-1 infection and exposure to
      viral proteins such as Tat and gp120 affect various aspects of microglial
      homeostasis including activation, cellular metabolism and cell cycle regulation,
      through pathways implicated in cellular stress responses including p38 mitogen
      activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB). We thus
      propose that the functions of human microglia evolve during both healthy and
      pathological aging. Aging-associated dysfunction of microglia comprises
      phenotypes resembling cellular senescence, which could contribute to cognitive
      impairments observed in various neurodegenerative diseases. In addition,
      microglia seems to develop characteristics that could be related to cellular
      senescence post-HIV-1 infection and after exposure to HIV-1 viral proteins.
      However, despite its potential role as a component of HAND and likely other
      neurocognitive disorders, microglia senescence has not been well characterized
      and should be the focus of future studies, which could have high translational
      relevance. GLIA 2017;65:431-446.

PMID- 27888539
TI  - Macrophage depletion impairs skeletal muscle regeneration: The roles of
      regulatory factors for muscle regeneration.
AB  - Though macrophages are essential for skeletal muscle regeneration, which is a
      complex process, the roles and mechanisms of the macrophages in the process of
      muscle regeneration are still not fully understood. The objective of this study
      is to explore the roles of macrophages and the mechanisms involved in the
      regeneration of injured skeletal muscle. One hundred and twelve C57BL/6 mice were
      randomly divided into muscle contusion and macrophages depleted groups. Their
      gastrocnemius muscles were harvested at the time points of 12 h, 1, 3, 5, 7, 14 d
      post-injury. The changes in skeletal muscle morphology were assessed by
      hematoxylin and eosin (HE) stain. The gene expression was analyzed by real-time
      polymerase chain reaction. The data showed that CL-liposomes treatment did affect
      the expression of myogenic regulatory factors (MyoD, myogenin) after injury. In
      addition, CL-liposomes treatment decreased the expression of regulatory factors
      of muscle regeneration (HGF, uPA, COX-2, IGF-1, MGF, FGF6) and increased the
      expression of inflammatory cytokines (TGF-beta1, TNF-alpha, IL-1beta, RANTES) in
      the late stage of regeneration. Moreover, there were significant correlations
      between macrophages and some regulatory factors (such as HGF, uPA) for muscle
      regeneration. These results suggested that macrophages depletion impairs skeletal
      muscle regeneration and that the regulatory factors for muscle regeneration may
      play important roles in this process.

PMID- 27888540
TI  - Higher dose of CD34+ peripheral blood stem cells is associated with better
      survival after haploidentical stem cell transplantation in pediatric patients.
AB  - Haploidentical stem cell transplantation (SCT) is increasingly used to treat
      pediatric patients with malignant or nonmalignant hematological disorders. The
      CD34+ dose of bone marrow or peripheral blood stem cells (PBSCs) has been shown
      to be an important determinant of the transplant outcome in adults under various
      preparative regimens. However, knowledge of the effect of the CD34+ dose in
      pediatric haploidentical SCT is limited. We analyzed the data of 348 pediatric
      patients (aged 2-18 years) with acute or chronic leukemia, myelodysplastic
      syndrome (MDS), and other hematological disorders that received a transplant
      between 2002 and 2012. The results of multivariate analysis showed that PBSC
      CD34+ counts greater than 1.01 * 106  kg-1 improved platelet engraftment,
      improved overall survival, and reduced nonrelapse mortality. In contrast, a
      higher PBSC CD34+ dose did not affect the incidence of acute or chronic graft
      versus-host disease, including engraftment syndrome. These data suggest that a
      PBSC CD34+ dose greater than 1.01 * 106  kg-1 is optimal for pediatric
      haploidentical SCT.

PMID- 27888541
TI  - TWEAK increases SIRT1 expression and promotes p53 deacetylation affecting human
      hepatic stellate cell senescence.
AB  - To detect the effects of tumor necrosis factor-like weak inducer of apoptosis
      (TWEAK) on SIRT1 expression and p53 deacetylation, involving cell senescence, in
      activated human hepatic stellate cell (HSC) in vitro, human HSC LX-2 was cultured
      with TWEAK for 24 h. The result showed that the expression of membrane receptor
      Fn14 was remarkably increased by TWEAK, which upregulated SIRT1 in LX-2 cells,
      detected by Western blotting and real-time PCR. The expression of p53 was not
      significantly altered; however, the ac-p53 was decreased. Furthermore, the
      viability of LX-2 cells was significantly enhanced by TWEAK. The activity of SA
      beta-Gal was notably inhibited, showing a suppressing effect of TWEAK on the
      senescence of activated HSC. Primary cultured HSC on days 7 and 11 was used to
      examine the expression of TWEAK, Fn14, SIRT1, and the activity of SA-beta-Gal.
      The result indicated that the mRNA of TWEAK, SIRT1, and Fn14 was all decreased on
      day 11 compared to that on day 7, and the activity of SA-beta-Gal was higher on
      day 11 than that on day 7. The present study suggested that TWEAK enhanced the
      expression of SIRT1 and decreased the acetylation of p53, probably inhibiting the
      senescence of activated HSC in vitro, which provides a molecular basis for TWEAK
      as a potential target in the therapy of liver fibrosis.

PMID- 27888542
TI  - Clinical Outcomes of Extended Versus Intermittent Infusion of
      Piperacillin/Tazobactam in Critically Ill Patients: A Prospective Clinical Trial.
AB  - STUDY OBJECTIVE: To determine whether critically ill patients receiving extended
      infusion (EI) piperacillin/tazobactam would have improved clinical outcomes
      compared with patients receiving intermittent infusions. DESIGN: Single-center,
      open-label, prospective study. SETTING: Twenty-two-bed intensive care unit (ICU)
      in a regional hospital in Hong Kong. PATIENTS: A total of 367 adults who had a
      diagnosis of either bacterial infection or neutropenic fever and had received
      treatment with piperacillin/tazobactam for at least 48 hours between December 1,
      2013, and August 31, 2015. INTERVENTION: Patients were assigned to receive
      piperacillin/tazobactam as either a 4-hour EI (182 patients [EI group]) or a 30
      minute intermittent infusion (185 patients [non-extended infusion (NEI) group]).
      MEASUREMENTS AND MAIN RESULTS: All patients were followed for at least 14 days
      after treatment assignment. The primary outcome was the 14-day mortality rate
      after initiation of piperacillin/tazobactam. Secondary outcomes included in
      hospital mortality rate, time to defervescence, duration of mechanical
      ventilatory support, length of ICU stay, and duration of hospital stay. Both
      groups demonstrated similar 14-day mortality (11.5% in the EI group vs 15.7% in
      the NEI group, p=0.29). The mean time to defervescence was significantly reduced
      in the EI group (4 days in the EI group vs 6 days in the NEI group, p=0.01); no
      significant differences between groups were noted in the other secondary
      outcomes. An Acute Physiology and Chronic Health Evaluation II score of 29.5 or
      higher was found to strongly predict 14-day mortality (p=0.03) by Classification
      and Regression Tree analysis. In the post hoc analyses, a 14-day mortality
      benefit was demonstrated in patients in the EI group in whom infectious organisms
      were identified (mortality rate 9.3% in the EI group vs 22.4% in the NEI group,
      p=0.01) and in whom respiratory tract infection was diagnosed (mortality rate
      8.9% in the EI group vs 18.7% in the NEI group, p=0.02). CONCLUSION: Both the EI
      and NEI groups demonstrated similar 14-day mortality. Post hoc subgroup analysis
      revealed a mortality benefit in patients in the EI group who had infectious
      organisms identified or were diagnosed with respiratory tract infections.

PMID- 27888543
TI  - Segmented simultaneous multi-slice diffusion weighted imaging with generalized
      trajectories.
AB  - PURPOSE: The purpose of this work is to develop and evaluate a single framework
      for the use of Cartesian and non-Cartesian segmented trajectories for rapid and
      robust simultaneous multislice (SMS) diffusion weighted imaging (DWI) at 3 Telsa
      (T). METHODS: A generalized SMS approach with intrinsic phase navigation using
      Multiplexed Sensitivity Encoding (MUSE) was developed. Segmented blipped
      controlled aliasing in parallel imaging echo planar imaging (EPI) and z-gradient
      modulated spiral trajectories were examined using SMS DWI scans at 3T with a 32
      channel head coil. RESULTS: The generalized SMS MUSE reconstruction framework was
      successful in significantly reducing artifacts for all trajectories. A DWI brain
      volume with a 67.5-mm height, 1.5-mm isotropic resolution, and 90 diffusion
      weightings was obtained in a scan time of 6 minutes. CONCLUSION: The MUSE
      technique can be generalized to allow for reconstruction of both Cartesian and
      non-Cartesian segmented trajectories. Magn Reson Med 78:1476-1481, 2017. (c) 2016
      International Society for Magnetic Resonance in Medicine.

PMID- 27888544
TI  - Conditioned medium: a new alternative for cryopreservation of equine umbilical
      cord mesenchymal stem cells.
AB  - Cryopreservation is a feasible alternative to maintaining several cell lines,
      particularly for immediate therapeutic use, transportation of samples, and
      implementation of new in vitro studies. This work parts from the hypothesis that
      the medium of cryopreservation composed by 90% of conditioned medium (CM)
      supports cryopreservation of equine umbilical cord intervascular matrix
      mesenchymal stem cells (UCIM-MSCs), allowing the maintenance of the biological
      properties for the establishment of cell banks intended for therapeutic use and
      in vitro studies. Thus, we evaluated the viability, apoptosis/necrosis rates,
      immunophenotypic profile (IP), chromosomal stability, clonicity, and
      differentiation potential of UCIM-MSCs cryopreserved with four different mediums
      (with FBS: M1, M3, M4 and without FBS: M2). After 3 months of cryopreservation,
      samples were thawed and analyzed. The potential of differentiation in the
      mesodermal lineages, clonicity, and the chromosomal stability were maintained
      after cryopreservation of UCIM-MSCs with medium containing FBS. Changes (P <
      0.05) at IP for some markers were observed at cells cryopreserved with medium M1
      M3. Only the UCIM-MSCs cryopreserved with the CM (M4) had similar viability post
      thaw (P = 0.23) when compared with fresh cells. We proved the hypothesis that the
      medium of cryopreservation containing CM supports the cryopreservation of UCIM
      MSCs, at the experimental conditions, being the medium that better maintains the
      biological characteristics observed at fresh cells. Thus, future studies of UCIM
      MSCs secretome should be conducted to better understand the beneficial and
      protective effects of the CM during the freezing process.

PMID- 27888546
TI  - Sex differences in depolarizing actions of GABAA receptor activation in rat
      embryonic hypothalamic neurons.
AB  - GABAA receptor activation exerts trophic actions in immature neurons through
      depolarization of resting membrane potential. The switch to its classical
      hyperpolarizing role is developmentally regulated. Previous results suggest that
      a hormonally biased sex difference exists at the onset of the switch in
      hypothalamic neurons. The aim of this work was to evaluate sex differences in
      GABAA receptor function of hypothalamic neurons before brain masculinization by
      gonadal hormones. Hypothalamic cells were obtained from embryonic day 16 male and
      female rat foetuses, 2 days before the peak of testosterone production by the
      foetal testis, and grown in vitro for 9 days. Whole-cell and perforated patch
      clamp recordings were carried out in order to measure several
      electrophysiological parameters. Our results show that there are more male than
      female neurons responding with depolarization to muscimol. Additionally, among
      cells with depolarizing responses, males have higher and longer lasting responses
      than females. These results highlight the relevance of differences in neural cell
      sex irrespective of exposure to sex hormones.

PMID- 27888545
TI  - Anti-angiogenic therapy affects the relationship between tumor vascular structure
      and function: A correlation study between micro-computed tomography angiography
      and dynamic contrast enhanced MRI.
AB  - PURPOSE: To compare the effects of two anti-angiogenic drugs, bevacizumab and a
      cytosolic phospholipase A2-alpha inhibitor (AVX235), on the relationship between
      vascular structure and dynamic contrast enhanced (DCE)-MRI measurements in a
      patient-derived breast cancer xenograft model. METHODS: Mice bearing MAS98.12
      tumors were randomized into three groups: bevacizumab-treated (n = 9), AVX235
      treated (n = 9), and control (n = 8). DCE-MRI was performed pre- and post
      treatment. Median initial area under the concentration-time curve (IAUC60 ) and
      volume transfer constant (Ktrans ) were computed for each tumor. Tumors were
      excised for ex vivo micro-CT (computed tomography) angiography, from which the
      vascular surface area (VSA) and fractional blood volume (FBV) were computed.
      Spearman correlation coefficients (rho) were computed to evaluate the
      associations between the DCE-MRI and micro-CT parameters. RESULTS: With the
      groups pooled, IAUC60 and Ktrans correlated significantly with VSA (rho = 0.475
      and 0.527; P = 0.019 and 0.008). There were no significant correlations within
      the control group. There were various significant correlations within the
      treatment groups, but the correlations in the bevacizumab group were of opposite
      sign, for example, Ktrans versus FBV: AVX235, rho = 0.800 (P = 0.014);
      bevacizumab, rho = -0.786 (P = 0.023). CONCLUSION: DCE-MRI measurements can
      highly depend on vascular structure. The relationship between vascular structure
      and function changed markedly after anti-angiogenic treatment. Magn Reson Med
      78:1513-1522, 2017. (c) 2016 International Society for Magnetic Resonance in
      Medicine.

PMID- 27888547
TI  - Towards a whole-genome sequence for rye (Secale cereale L.).
AB  - We report on a whole-genome draft sequence of rye (Secale cereale L.). Rye is a
      diploid Triticeae species closely related to wheat and barley, and an important
      crop for food and feed in Central and Eastern Europe. Through whole-genome
      shotgun sequencing of the 7.9-Gbp genome of the winter rye inbred line Lo7 we
      obtained a de novo assembly represented by 1.29 million scaffolds covering a
      total length of 2.8 Gbp. Our reference sequence represents nearly the entire low
      copy portion of the rye genome. This genome assembly was used to predict 27 784
      rye gene models based on homology to sequenced grass genomes. Through
      resequencing of 10 rye inbred lines and one accession of the wild relative S.
      vavilovii, we discovered more than 90 million single nucleotide variants and
      short insertions/deletions in the rye genome. From these variants, we developed
      the high-density Rye600k genotyping array with 600 843 markers, which enabled
      anchoring the sequence contigs along a high-density genetic map and establishing
      a synteny-based virtual gene order. Genotyping data were used to characterize the
      diversity of rye breeding pools and genetic resources, and to obtain a genome
      wide map of selection signals differentiating the divergent gene pools. This rye
      whole-genome sequence closes a gap in Triticeae genome research, and will be
      highly valuable for comparative genomics, functional studies and genome-based
      breeding in rye.

PMID- 27888548
TI  - Effects of seasonality, transport pathway, and spatial structure on greenhouse
      gas fluxes in a restored wetland.
AB  - Wetlands can influence global climate via greenhouse gas (GHG) exchange of carbon
      dioxide (CO2 ), methane (CH4 ), and nitrous oxide (N2 O). Few studies have
      quantified the full GHG budget of wetlands due to the high spatial and temporal
      variability of fluxes. We report annual open-water diffusion and ebullition
      fluxes of CO2 , CH4 , and N2 O from a restored emergent marsh ecosystem. We
      combined these data with concurrent eddy-covariance measurements of whole
      ecosystem CO2 and CH4 exchange to estimate GHG fluxes and associated radiative
      forcing effects for the whole wetland, and separately for open-water and
      vegetated cover types. Annual open-water CO2 , CH4 , and N2 O emissions were 915
      +/- 95 g C-CO2  m-2  yr-1 , 2.9 +/- 0.5 g C-CH4  m-2  yr-1 , and 62 +/- 17 mg N
      N2 O m-2  yr-1 , respectively. Diffusion dominated open-water GHG transport,
      accounting for >99% of CO2 and N2 O emissions, and ~71% of CH4 emissions.
      Seasonality was minor for CO2 emissions, whereas CH4 and N2 O fluxes displayed
      strong and asynchronous seasonal dynamics. Notably, the overall radiative forcing
      of open-water fluxes (3.5 +/- 0.3 kg CO2 -eq m-2  yr-1 ) exceeded that of
      vegetated zones (1.4 +/- 0.4 kg CO2 -eq m-2  yr-1 ) due to high ecosystem
      respiration. After scaling results to the entire wetland using object-based cover
      classification of remote sensing imagery, net uptake of CO2 (-1.4 +/- 0.6 kt CO2 
      eq yr-1 ) did not offset CH4 emission (3.7 +/- 0.03 kt CO2 -eq yr-1 ), producing
      an overall positive radiative forcing effect of 2.4 +/- 0.3 kt CO2 -eq yr-1 .
      These results demonstrate clear effects of seasonality, spatial structure, and
      transport pathway on the magnitude and composition of wetland GHG emissions, and
      the efficacy of multiscale flux measurement to overcome challenges of wetland
      heterogeneity.

PMID- 27888549
TI  - Microscope-assisted hepatic artery reconstruction in adult living donor liver
      transplantation-A review of 325 consecutive cases in a single center.
AB  - BACKGROUND: Despite the technical and medical improvements in the recent years,
      hepatic artery thrombosis (HAT) remains a devastating complication after living
      donor liver transplantation (LDLT). We described our surgical techniques and
      monitoring protocols for hepatic artery reconstruction. We reported one of the
      lowest incidence rates of HAT in the literature. METHODS: Between 2008 and 2015,
      a total of 325 LDLTs performed at our institute were retrospectively analyzed.
      Under microscope assistance, all hepatic artery anastomosis were performed in a
      risk-free and back-wall first manner. We collected donors' and recipients'
      demographics, operative procedures, and outcome. RESULTS: A total of 325 adult
      LDLTs were enrolled in the study. Of these, 297(91.4%) were right liver graft.
      The mean diameter of the hepatic arteries of the graft was 1.9 +/- 0.3 mm. A
      single HA anastomosis was performed in 310 patients (95.4%). The 1-, 3-, and 5
      year overall patient survival rates were 84.8%, 76.8%, and 75.2%, respectively.
      Only one (0.3%) episode of HAT was encountered in our series. The patient was
      treated successfully with nonsurgical management. CONCLUSION: Our study showed
      that the occurrence of HAT is avoidable. Identifying risk factors associated with
      HAT, meticulous surgical techniques, and careful routine flow monitoring are
      mandatory to avoid disastrous complications.

PMID- 27888550
TI  - Concise Review: Mesenchymal Stem (Stromal) Cells: Biology and Preclinical
      Evidence for Therapeutic Potential for Organ Dysfunction Following Trauma or
      Sepsis.
AB  - Several experimental studies have provided evidence that bone-marrow derived
      mesenchymal stem (stromal) cells (MSC) may be effective in treating critically
      ill surgical patients who develop traumatic brain injury, acute renal failure, or
      the acute respiratory distress syndrome. There is also preclinical evidence that
      MSC may be effective in treating sepsis-induced organ failure, including evidence
      that MSC have antimicrobial properties. This review considers preclinical studies
      with direct relevance to organ failure following trauma, sepsis or major
      infections that apply to critically ill patients. Progress has been made in
      understanding the mechanisms of benefit, including MSC release of paracrine
      factors, transfer of mitochondria, and elaboration of exosomes and microvesicles.
      Regardless of how well they are designed, preclinical studies have limitations in
      modeling the complexity of clinical syndromes, especially in patients who are
      critically ill. In order to facilitate translation of the preclinical studies of
      MSC to critically ill patients, there will need to be more standardization
      regarding MSC production with a focus on culture methods and cell
      characterization. Finally, well designed clinical trials will be needed in
      critically ill patient to assess safety and efficacy. Stem Cells 2017;35:316-324.

PMID- 27888552
TI  - Initial clinical experience with the Medtronic Micro Vascular PlugTM in
      transcatheter occlusion of PDAs in extremely premature infants.
AB  - OBJECTIVES: To describe the early multicenter, clinical experience with the
      Medtronic Micro Vascular PlugTM (MVP) for the occlusion of patent ductus
      arteriosus (PDA) in premature infants. BACKGROUND: The MVP is a large diameter
      plug that can be delivered through a microcatheter for occlusion of abnormal
      blood vessels. METHODS: A Retrospective review of PDA embolization procedures
      performed in two centers using the MVP was performed. RESULTS: Fifteen premature
      infants underwent attempted PDA occlusion using the MVP. The gestational age and
      birth weight were 25.6 +/- 2.5 weeks and 735 +/- 251 g, respectively. The median
      weight and age at the time of the procedure were 1,210 g (700-3,500 g) and 4.5
      weeks (2-12 weeks), respectively. Median procedure and fluoroscopy times were 45
      and 6.5 min, respectively. The median radiation and contrast doses were 19.7 mGy
      and 2.4 mL/kg, respectively. Antegrade occlusion was successfully achieved in 13
      patients <2 kg with only femoral venous access aided by echo guidance. The two
      patients >2 kg had arterial access and attempted retrograde occlusion; one of
      which was unsuccessful due to the PDA being short and wide. Complete closure was
      observed in 13 of 14 successful procedures (93%), with one patient having a small
      residual shunt that was not seen on follow-up. There were no complications
      related to the procedure or noted during follow-up (Median 11 months).
      CONCLUSIONS: The MVP is a new, large-diameter vascular embolization device that
      may be useful for the occlusion of PDA in extremely small, premature infants. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27888553
TI  - Left Lobe Auxiliary Liver Transplantation for End-stage Hepatitis B Liver
      Cirrhosis.
AB  - Auxiliary liver transplantation (ALT) for hepatitis B virus (HBV)-related liver
      cirrhosis previously showed poor results, because the native liver was a
      significant source of HBV recurrence and the graft could be rapidly destroyed by
      HBV infection in an immunosuppressive condition. Four patients with HBV-related
      liver cirrhosis were unable to undergo orthotopic liver transplantation because
      the only available grafts of left lobe were too small. Under entecavir-based anti
      HBV treatment, they underwent ALT in which the recipient left liver was removed
      and the small left lobe graft was implanted in the corresponding space. The mean
      graft weight/recipient weight was 0.49% (range, 0.38%-0.55%). One year after
      transplantation, the graft sizes were increased to 273% and the remnant livers
      were decreased to 44%. Serum HBV DNA was persistently undetectable. Periodic
      graft biopsy showed no signs of tissue injury and negative immunostaining for
      hepatitis B surface antigen and hepatitis B core antigen. After a mean follow-up
      period of 21 months, all patients live well with normal graft function. Our study
      suggests that ALT for HBV-related liver cirrhosis is feasible under entecavir
      based anti-HBV treatment. Successful application of small left livers in end
      stage liver cirrhosis may significantly increase the pool of left liver grafts
      for adult patients.

PMID- 27888551
TI  - Selective Targeting of High-Affinity LFA-1 Does Not Augment Costimulation
      Blockade in a Nonhuman Primate Renal Transplantation Model.
AB  - Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to
      calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates
      of early acute rejection. These early rejections are mediated in part by memory T
      cells, which have reduced dependence on the pathway targeted by belatacept and
      increased adhesion molecule expression. One such molecule is leukocyte function
      antigen (LFA)-1. LFA-1 exists in two forms: a commonly expressed, low-affinity
      form and a transient, high-affinity form, expressed only during activation. We
      have shown that antibodies reactive with LFA-1 regardless of its configuration
      are effective in eliminating memory T cells but at the cost of impaired
      protective immunity. Here we test two novel agents, leukotoxin A and AL-579, each
      of which targets the high-affinity form of LFA-1, to determine whether this more
      precise targeting prevents belatacept-resistant rejection. Despite evidence of ex
      vivo and in vivo ligand-specific activity, neither agent when combined with
      belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a
      ceiling of toxicity before efficacy, while AL-579 failed to significantly alter
      the peripheral immune response. These data, and prior studies, suggest that LFA-1
      blockade may not be a suitable adjuvant agent for CoB-resistant rejection.

PMID- 27888554
TI  - A high-resolution genetic map of the cereal crown rot pathogen Fusarium
      pseudograminearum provides a near-complete genome assembly.
AB  - Fusarium pseudograminearum is an important pathogen of wheat and barley,
      particularly in semi-arid environments. Previous genome assemblies for this
      organism were based entirely on short read data and are highly fragmented. In
      this work, a genetic map of F. pseudograminearum has been constructed for the
      first time based on a mapping population of 178 individuals. The genetic map,
      together with long read scaffolding of a short read-based genome assembly, was
      used to give a near-complete assembly of the four F. pseudograminearum
      chromosomes. Large regions of synteny between F. pseudograminearum and F.
      graminearum, the related pathogen that is the primary causal agent of cereal head
      blight disease, were previously proposed in the core conserved genome, but the
      construction of a genetic map to order and orient contigs is critical to the
      validation of synteny and the placing of species-specific regions. Indeed, our
      comparative analyses of the genomes of these two related pathogens suggest that
      rearrangements in the F. pseudograminearum genome have occurred in the chromosome
      ends. One of these rearrangements includes the transposition of an entire gene
      cluster involved in the detoxification of the benzoxazolinone (BOA) class of
      plant phytoalexins. This work provides an important genomic and genetic resource
      for F. pseudograminearum, which is less well characterized than F. graminearum.
      In addition, this study provides new insights into a better understanding of the
      sexual reproduction process in F. pseudograminearum, which informs us of the
      potential of this pathogen to evolve.

PMID- 27888556
TI  - Evaluation of quality of kidneys from donation after circulatory death/expanded
      criteria donors by parameters of machine perfusion.
AB  - AIM: To investigate whether the parameters of machine perfusion could predict the
      quality of kidneys from donation after circulatory death (DCD) donors and
      expanded criteria donors (ECD). METHODS: Fifty-eight kidneys from DCD/ECD donors
      were harvested in our hospital from July 2011 to August 2014. All kidneys were
      preserved with machine perfusion (Life Port), and parameters of machine perfusion
      were collected. All kidneys were biopsied before transplantation. The primary
      endpoints were delayed graft function (DGF), graft loss and patient death.
      RESULTS: After kidney transplantation, 26 patients (44.8%) had DGF. We chose 1 h
      RI as a predictive parameter to predict DGF after transplant, and made the ROC
      curve. The ROC curve showed that 1 h RI = 0.4 was the best cut-off point for
      predicting DGF after transplant. The sensitivity was 61.54%, and the specificity
      was 81.25%. Fifty-eight recipients were divided into two groups according to 1 h
      RI of machine perfusion. 22 cases in high RI group (RI > 0.4) and 36 cases in low
      RI group (RI <=0.4). DGF rate was significantly higher in the high RI group
      (72.7% vs. 27.8%). One year serum creatinine levels were also significantly
      higher in the high RI group (P < 0.05). Acute rejection rate and 1 year graft and
      patient survival were comparable. CONCLUSIONS: One hour RI of machine perfusion
      is associated with DGF and 1 year graft function in DCD/ECD kidney
      transplantation, and may be a non-invasive tool for evaluating quality of DCD/ECD
      kidneys.

PMID- 27888555
TI  - Renal Operational Tolerance Is Associated With a Defect of Blood Tfh Cells That
      Exhibit Impaired B Cell Help.
AB  - Renal operationally tolerant patients (TOL) display a defect in B cell
      differentiation, with a deficiency in plasma cells. Recently described, T
      follicular helper (Tfh) cells play a critical role in B cell differentiation. We
      analyzed blood Tfh subsets in TOL and transplanted patients with stable graft
      function under immunosuppression (STA). We observed a reduced proportion of blood
      activated and highly functional Tfh subsets in TOL, without affecting Tfh
      absolute numbers. Functionally, Tfh cells from TOL displayed a modified gene
      expression profile, failed to produce interleukin-21, and were unable to induce
      IgG production by naive B cells. This Tfh defect is linked to a low incidence of
      postgraft de novo donor-specific antibody (dnDSA) immunization, suggesting that
      the lack of Tfh cells in TOL may induce a protolerogenic environment with reduced
      risk of developing dnDSA. Finally, we showed that elevated Tfh in STA precedes
      the occurrence of dnDSA during an alloresponse. These data provide new insights
      into the mechanisms of antibody response in operational tolerance. Disrupted
      homeostasis and impaired Tfh function in TOL could lead to a reduced risk of
      developing dnDSA and suggest a predictive role of blood Tfh cells on the
      occurrence of dnDSA in transplant recipients.

PMID- 27888557
TI  - Adoptive transfer of T regulatory cells inhibits lipopolysaccharide-induced
      inflammation in fetal brain tissue in a late-pregnancy preterm birth mouse model.
AB  - To evaluate the effect of regulatory T cells (Tregs) on the inflammation
      resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs
      isolated from pregnant mice were transferred into model mice, and the expression
      levels of fork head family transcription factor (Foxp3), interleukin-6 (IL-6),
      CD68 (a marker of microglia), and toll-like receptor 4 (TLR-4) were assessed in
      the fetal brain tissue. Foxp3, IL-6, and TLR-4 expression were detected by
      polymerase chain reaction and Western blot; CD68 expression level was detected
      using immunochemical analysis. Foxp3, IL-6, TLR-4, and CD68 expressions in fetal
      brain were significantly induced by maternal LPS administration, and the
      increased expression levels were markedly reduced by adoptive transfer of Tregs.
      Maternal LPS exposure significantly induced inflammation in perinatal brain
      tissue, and Tregs negatively regulated this LPS-induced inflammation.

PMID- 27888558
TI  - Spontaneous Single-Copy Loss of TP53 in Human Embryonic Stem Cells Markedly
      Increases Cell Proliferation and Survival.
AB  - Genomic aberrations have been identified in many human pluripotent stem cell
      (hPSC) cultures. Commonly observed duplications in portions of chromosomes 12p
      and 17q have been associated with increases in genetic instability and resistance
      to apoptosis, respectively. However, the phenotypic consequences related to
      sporadic mutations have not been evaluated to date. Here, we report on the
      effects of a single-copy deletion of the chr17p13.1 region, a sporadic mutation
      that spontaneously arose independently in several subclones of a human embryonic
      stem cell culture. Compared to cells with two normal copies of chr17p13.1 ("wild
      type"), the cells with a single-copy deletion of this region ("mutant") displayed
      a selective advantage when exposed to stressful conditions, and retained a higher
      percentage of cells expressing the pluripotency marker POU5F1/OCT4 after 2 weeks
      of in vitro differentiation. Knockdown of TP53, which is a gene encompassed by
      the deleted region, in wild-type cells mimicked the chr17p13.1 deletion
      phenotype. Thus, sporadic mutations in hPSCs can have phenotypic effects that may
      impact their utility for clinical applications. Stem Cells 2017;35:872-885.

PMID- 27888559
TI  - Ten-year all-cause mortality and its association with vision among Indigenous
      Australians within Central Australia: the Central Australian Ocular Health Study.
AB  - BACKGROUND: No studies to date have explored the association of vision with
      mortality in Indigenous Australians. We aimed to determine the 10-year all-cause
      mortality and its associations among Indigenous Australians living in Central
      Australia. DESIGN: Prospective observational cohort study. PARTICIPANTS: A total
      of 1257 (93.0%) of 1347 patients from The Central Australian Ocular Health Study,
      over the age of 40 years, were available for follow-up during a 10-year period.
      METHODS: All-cause mortality and its associations with visual acuity, age and
      gender were analysed. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: All
      cause mortality was 29.3% at the end of 10 years. Mortality increased as age of
      recruitment increased: 14.2% (40-49 years), 22.6% (50-59 years), 50.3% (60 years
      or older) (chi = 59.15; P < 0.00001). Gender was not associated with mortality as
      an unadjusted variable, but after adjustment with age and visual acuity, women
      were 17.0% less likely to die (t = 2.09; P = 0.037). Reduced visual acuity was
      associated with increased mortality rate (5% increased mortality per one line of
      reduced visual acuity; t = 4.74; P < 0.0001) after adjustment for age, sex,
      diabetes and hypertension. CONCLUSIONS: The 10-year all-cause mortality rate of
      Indigenous Australians over the age of 40 years and living in remote communities
      of Central Australia was 29.3%. This is more than double that of the Australian
      population as a whole. Mortality was significantly associated with visual acuity
      at recruitment. Further work designed to better understand this association is
      warranted and may help to reduce this disparity in the future.

PMID- 27888560
TI  - Do invasive alien plants benefit more from global environmental change than
      native plants?
AB  - Invasive alien plant species threaten native biodiversity, disrupt ecosystem
      functions and can cause large economic damage. Plant invasions have been
      predicted to further increase under ongoing global environmental change. Numerous
      case studies have compared the performance of invasive and native plant species
      in response to global environmental change components (i.e. changes in mean
      levels of precipitation, temperature, atmospheric CO2 concentration or nitrogen
      deposition). Individually, these studies usually involve low numbers of species
      and therefore the results cannot be generalized. Therefore, we performed a
      phylogenetically controlled meta-analysis to assess whether there is a general
      pattern of differences in invasive and native plant performance under each
      component of global environmental change. We compiled a database of studies that
      reported performance measures for 74 invasive alien plant species and 117 native
      plant species in response to one of the above-mentioned global environmental
      change components. We found that elevated temperature and CO2 enrichment
      increased the performance of invasive alien plants more strongly than was the
      case for native plants. Invasive alien plants tended to also have a slightly
      stronger positive response to increased N deposition and increased precipitation
      than native plants, but these differences were not significant (N deposition: P =
      0.051; increased precipitation: P = 0.679). Invasive alien plants tended to have
      a slightly stronger negative response to decreased precipitation than native
      plants, although this difference was also not significant (P = 0.060). So while
      drought could potentially reduce plant invasion, increases in the four other
      components of global environmental change considered, particularly global warming
      and atmospheric CO2 enrichment, may further increase the spread of invasive
      plants in the future.

PMID- 27888563
TI  - Qualities of robust systematic reviews and theoretical frameworks: a response to
      Backholer and Peeters.

PMID- 27888561
TI  - Novel hepato-preferential basal insulin peglispro (BIL) does not differentially
      affect insulin sensitivity compared with insulin glargine in patients with type 1
      and type 2 diabetes.
AB  - AIMS: Basal insulin peglispro (BIL) is a novel PEGylated basal insulin with a
      flat pharmacokinetic and glucodynamic profile and reduced peripheral effects,
      which results in a hepato-preferential action. In Phase 3 trials, patients with
      T1DM treated with BIL had lower prandial insulin requirements, yet improved
      prandial glucose control, relative to insulin glargine (GL). We hypothesized that
      this may be because of an enhanced sensitivity to prandial insulin with BIL
      resulting from lower chronic peripheral insulin action. MATERIALS AND METHODS:
      Two open-label, randomized, 2-period crossover clinical studies were conducted in
      28 patients with T1DM and 24 patients with T2DM. In each study period, patients
      received once-daily, individualized, stable, subcutaneous doses of BIL or GL for
      5 weeks before a euglycaemic 2-step hyperinsulinemic clamp procedure (with [6,6-
      2 H2 ]-glucose in 12 of the patients with T1DM). M-values were derived from the
      clamp procedure for all patients, with rate of glucose appearance (Ra) and
      disappearance (Rd) and insulin sensitivity index (SI) determined from the clamps
      with [6,6- 2 H2 ]-glucose. RESULTS: There were no statistically significant
      differences between BIL and GL in key measures of hepatic (% Ra suppression
      during the low-dose insulin infusion; 78.7% with BIL, 81.8% with GL) or
      peripheral (M-value and M/I during the high-dose insulin infusion, Rd and SI)
      insulin sensitivity in patients with T1DM or T2DM. CONCLUSIONS: The need to
      reduce prandial insulin observed with BIL during phase 3 trials cannot be
      explained by the differential effects of BIL and GL on sensitivity to prandial
      insulin in either T1DM or T2DM.

PMID- 27888562
TI  - Parainfluenza 3 Infections Early After Kidney or Simultaneous Pancreas-Kidney
      Transplantation.
AB  - Parainfluenza virus (PIV) can cause serious infections after hematopoietic stem
      cell or lung transplantation. Limited data exist about PIV infections after
      kidney transplantation. We describe an outbreak of PIV-3 in a transplant unit.
      During the outbreak, 45 patients were treated on the ward for postoperative care
      after kidney or simultaneous pancreas-kidney (SPK) transplantation. Overall, 29
      patients were tested for respiratory viruses (12 patients with respiratory
      symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs using
      polymerase chain reaction. PIV-3 infection was confirmed in 12 patients. One
      patient remained asymptomatic. In others, symptoms were mostly mild upper
      respiratory tract symptoms and subsided within a few days with symptomatic
      treatment. Two patients suffered from lower respiratory tract symptoms (dyspnea,
      hypoxemia, pulmonary infiltrates in chest computed tomography) and required
      supplemental oxygen. Four of six SPK patients and eight of 39 of kidney
      transplant patients were infected with PIV (p = 0.04). In patients with follow-up
      tests, PIV-3 shedding was still detected 11-16 days after diagnosis. Despite
      rapid isolation of symptomatic patients, PIV-3 findings were diagnosed within 24
      days, and the outbreak ceased only after closing the transplant ward temporarily.
      In conclusion, PIV-3 infections early after kidney or SPK transplantation were
      mostly mild. PIV-3 easily infected immunosuppressed transplant recipients, with
      prolonged viral shedding.

PMID- 27888564
TI  - Communicating with children and families about obesity and weight-related topics:
      a scoping review of best practices.
AB  - BACKGROUND: Healthcare professionals have called for direction on how best to
      communicate about weight-related topics with children and families. Established
      scoping review methodology was used to answer the question: 'How can healthcare
      professionals best communicate with children and their families about obesity and
      weight-related topics?' METHODS: We searched four scientific databases, two grey
      literature repositories and 14 key journals (2005-2016). Inclusion criteria were
      (i) children up to and including 18 years of age and/or their parents; (ii)
      communication about healthy weight, overweight, obesity or healthy/active living;
      and (iii) healthcare setting. RESULTS: Thirty-two articles were included.
      Evidence-based best practices were largely absent from the literature, although
      the following guiding principles were identified: (i) include all stakeholders in
      discussions; (ii) raise the topic of weight and health early and regularly; (iii)
      use strengths-based language emphasizing health over weight; (iv) use
      collaborative goal-setting to engage children and parents and (v) augment
      discussions with appropriate tools and resources. Guidance on how to implement
      these principles and how to negotiate relevant contextual factors (e.g. age,
      culture and disability) is still needed. CONCLUSION: Despite agreement on a
      number of guiding principles, evidence-based weight-related communication best
      practices are lacking. Rigorous, empirical evaluations of communication
      approaches are urgently required, especially those that include children's
      perspectives.

PMID- 27888566
TI  - Functional expression of G protein-coupled receptor 30 in immature rat epididymal
      epithelium.
AB  - The aim of this study is to investigate the functional role of G protein-coupled
      receptor 30 (GPR30) in the epididymis. We found that GPR30 is expressed in the
      epithelium of the immature rat epididymis and is involved in chloride secretion
      into the caudal epididymis lumen. The short-circuit current (Isc) experiments
      showed that in primary cultured caudal epididymis epithelium, activation of GPR30
      by its specific agonist G1 induced a mono-phasic current increase, and G15, the
      specific antagonist of GPR30, could completely inhibit the current induced by G1.
      The G1-induced Isc was largely blocked by application of the non-specific
      chloride channel inhibitor diphenylamine-dicarboxylic acid (DPC), or by the
      cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTRinh-172
      , suggesting that the current was mainly mediated through CFTR. In addition,
      after stimulating GPR30 by G1, the intracellular concentration of cAMP in the
      epithelium was significantly increased, indicating that the cAMP signal pathway
      is involved and could be responsible for the CFTR activation. Finally, to further
      investigate the function of GPR30 in vivo, G15 was administrated into rats
      subcutaneously. The osmotic pressure of the micro perfusion solution from
      epididymis was measured and the sperms were collected. Results showed that there
      was an osmotic pressure increase of the perfusion solution from G15 treated rats.
      When the GPR30 was inhibited by G15 endogenously, the motility of sperms
      decreased. Our data demonstrated that GPR30 is involved in the formation of
      caudal epididymis fluid micro-environment thus affecting sperm motility.

PMID- 27888567
TI  - Chiral separation of benzothiazole derivatives of amino acids using capillary
      zone electrophoresis.
AB  - A method for the separation of enantiomers of leucine and phenylalanine
      benzothiazole derivatives as potential antimicrobial agents was developed using
      capillary zone electrophoresis with a dual cyclodextrin (CD) system. The best
      resolution of enantiomers was achieved in 100 mmol/L phosphate background
      electrolyte (pH 3.5) with the dual CD system consisting of 10 mmol/L of beta-CD
      with 10 mmol/L of 2-hydroxypropyl-beta-cyclodextrin for leucine derivative and 10
      mmol/L of 2-hydroxypropyl-gamma-cyclodextrin for phenylalanine derivative,
      respectively. Under the optimal conditions, the highest enantioresolution of 1.25
      was achieved in a noncoated-fused silica capillary at 17 degrees C and 24 kV
      applied voltage.

PMID- 27888565
TI  - Applying Mass Cytometry to the Analysis of Lymphoid Populations in
      Transplantation.
AB  - Single-cell flow cytometric techniques have been indispensable to improving our
      understanding of the phenotype and function of immune cell subsets that are
      important in both rejection and tolerance after transplant. Mass cytometry, or
      cytometry by time of flight, is a single-cell-based platform that utilizes
      antibodies conjugated to rare heavy metal ions for analysis of cellular proteins
      by a time-of-flight mass spectrometer. This new technology allows for the
      evaluation of >40 simultaneous cellular parameters in a single sample because the
      limitation of spectral overlap, seen in conventional flow cytometry, is
      eliminated. In this review, we discuss the current state of mass cytometry,
      describe the advantages and disadvantages compared with multiparameter flow
      cytometry, introduce novel methods of high-dimensional data analysis and
      visualization, and review some recent studies using mass cytometry to profile the
      immune systems of healthy people and transplant recipients.

PMID- 27888568
TI  - Facile preparation of a polydopamine-based monolith for multiple monolithic fiber
      solid-phase microextraction of triazine herbicides in environmental water
      samples.
AB  - A new multiple monolithic fiber solid-phase microextraction using a polydopamine
      based monolith as the extraction medium is proposed. The monolith was synthesized
      by facile in situ copolymerization of N-methacryldopamine and dual cross-linkers
      (divinylbenzene/ethylenedimethacrylate) in the presence of N,N-dimethylformamide.
      The effect of the contents of N-methacryldopamine and porogen in the
      polymerization mixture on the extraction performance was investigated thoroughly.
      A series of characterization studies was performed to validate the structure and
      properties of the monolith. The prepared multiple monolithic fibers were used for
      the extraction of triazine herbicides in environmental water samples. After the
      optimization of the extraction parameters, a convenient, sensitive, cost
      effective, and environmentally friendly method for the determination of trace
      triazine herbicides in water samples was developed by coupling multiple
      monolithic fibers solid-phase microextraction with high-performance liquid
      chromatography and diode array detection. The results indicated that the limits
      of detection and quantification for the target compounds were 0.031-0.14 and 0.10
      0.45 MUg/L, respectively. Good precision and reproducibility were obtained with
      the relative standard deviations below 10%. The developed method was applied to
      the analysis of the triazine herbicides in different water samples (lake, river,
      and farmland waters). The recoveries of the method were in the range between 79.6
      and 117%.

PMID- 27888569
TI  - Providing Coverage for the Unique Lifelong Health Care Needs of Living Kidney
      Donors Within the Framework of Financial Neutrality.
AB  - Organ donation should neither enrich donors nor impose financial burdens on them.
      We described the scope of health care required for all living kidney donors,
      reflecting contemporary understanding of long-term donor health outcomes;
      proposed an approach to identify donor health conditions that should be covered
      within the framework of financial neutrality; and proposed strategies to pay for
      this care. Despite the Affordable Care Act in the United States, donors continue
      to have inadequate coverage for important health conditions that are donation
      related or that may compromise postdonation kidney function. Amendment of
      Medicare regulations is needed to clarify that surveillance and treatment of
      conditions that may compromise postdonation kidney function following donor
      nephrectomy will be covered without expense to the donor. In other countries
      lacking health insurance for all residents, sufficient data exist to allow the
      creation of a compensation fund or donor insurance policies to ensure appropriate
      care. Providing coverage for donation-related sequelae as well as care to
      preserve postdonation kidney function ensures protection against the financial
      burdens of health care encountered by donors throughout their lives. Providing
      coverage for this care should thus be cost-effective, even without considering
      the health care cost savings that occur for living donor transplant recipients.

PMID- 27888570
TI  - Deep eutectic solvents for the purification of chloromycetin and thiamphenicol
      from milk.
AB  - Deep eutectic solvents were used in both dispersive liquid-liquid microextraction
      and solid-phase extraction for the purification of chloromycetin and
      thiamphenicol from milk. In the dispersive liquid-liquid microextraction
      procedure, deep eutectic solvents mixed with chloroform at different ratios (0:1
      5:1, v/v) were used as the extraction agent to optimize the procedure, and the
      ratio of 2:1 v/v was found to be the best extraction agent with 87.23 and 83.17%
      recoveries of chloromycetin and thiamphenicol, respectively. Furthermore, deep
      eutectic solvents were also used to modify molecular imprinted polymers in solid
      phase extraction procedure, and the polymers were used to purify chloromycetin
      and thiamphenicol from milk. Fourier transform infrared spectroscopy, and nuclear
      magnetic resonance spectroscopy were used to characterize the polymers. The solid
      phase extraction recoveries with deep eutectic solvents with molecularly
      imprinted polymers (chloromycetin and thiamphenicol, two templates), molecularly
      imprinted polymers (without deep eutectic solvents), and nonimprinted polymers
      (without a template) for chloromycetin were 91.23, 82.64, and 57.3%,
      respectively, and recoveries for thiamphenicol were 87.02, 79.03, and 52.27%,
      respectively. The recoveries of chloromycetin and thiamphenicol from milk in the
      solid-phase extraction procedure were higher than using deep eutectic solvents
      mixed with chloroform as the extraction agent in the dispersive liquid-liquid
      microextraction procedure.

PMID- 27888571
TI  - Melody valve implantation within freestyle stentless porcine aortic heterograft.
AB  - BACKGROUND: The Melody transcatheter pulmonary valve has been implanted
      successfully worldwide since its first implant in 2000. The vast majority of
      these valves have been implanted in pulmonary homografts. In our institution, the
      most common valve used for pulmonary valve replacement is the Medtronic Freestyle
      stentless porcine aortic heterograft. OBJECTIVE: We describe our experience
      implanting the Melody valve within the Freestyle heterograft. METHODS:
      Retrospective chart review was performed. RESULTS: Between June 2012 and June
      2015, 19 Melody valves were placed within Freestyle heterografts. The most common
      indication for intervention was pulmonary stenosis. Following pre-stent and
      Melody valve implantation, right ventricle-to-pulmonary artery gradient decreased
      from 38.1 +/- 12.1 to 10 +/- 4.7 mm Hg (P < 0.001), and right ventricular
      pressure decreased from 61.7 +/- 17.8 to 35.6 +/- 10.2 mm Hg (P < 0.001). Two
      procedural adverse events occurred. At median follow-up of 24 months (range 2-48
      months), no patients had mean right ventricular outflow tract gradients >30 mm Hg
      or worse than mild insufficiency. No valve reinterventions have been necessary
      and no episodes of endocarditis have been observed. CONCLUSIONS: The Melody valve
      can be implanted successfully within a stentless aortic bioprosthesis with good
      short- and intermediate-term longevity. (c) 2016 Wiley Periodicals, Inc.

PMID- 27888572
TI  - Adverse Effect Profile of Topical Ocular Administration of Fingolimod for
      Treatment of Dry Eye Disease.
AB  - Fingolimod is a promising prodrug in attenuating multiple sclerosis and
      prolonging survival of organ allograft, with many other protective effects. Its
      mechanism of action is related to the internalization of sphingosine 1-phosphate
      receptors (S1PRs). Our previous study indicated that fingolimod eyedrops was
      efficacious in inhibiting ocular inflammation in a dry eye disease (DED) model of
      non-obese diabetic (NOD) mice. In the current study, we evaluated potential
      adverse effects of fingolimod eyedrops. Inbred 10-week-old BALB/c mice were
      randomly divided into four groups, fingolimod-treated groups at three different
      concentrations (0.01%, 0.1% and 0.5%) and a negative control group without
      intervention. Our results showed that in the 0.5% fingolimod group, adverse
      effects such as photophobia, catacleisis and corneal oedema were observed after 1
      week of treatment. 1 month later, corneal opacity, oedema and neovascularization
      persisted till the mice were killed 2 months later. In contrast, there was no
      significant abnormality in the negative control group, and 0.01% and 0.1%
      fingolimod-treated groups. During a 2-month treatment period, we did not detect
      fingolimod, nor significant change in blood cells in peripheral blood, nor
      pathological changes in retina and systemic organs. Combined with our previous
      study and the current results, we recommend that an optimal range of safe and
      effective concentration of fingolimod as eyedrops is between 0.005% and 0.1%.

PMID- 27888573
TI  - B-cell activating factor, a predictor of antibody mediated rejection in kidney
      transplantation recipients.
AB  - AIM: Donor-specific antibody (DSA) is a widely-used biomarker for antibody
      mediated rejection (ABMR) but correctly indicates only 30-40% of patients with
      ABMR. Additional biomarkers of ABMR in kidney transplant recipients are needed.
      METHODS: All 68 kidney transplanted-recipients enrolled in this study were
      negative for graft rejection as determined by surveillance-biopsy ELISA at day 7
      post-transplantation. Allograft biopsy was then performed at 6 months post
      transplantation for subclinical-ABMR detection. Recipients were stratified by pre
      transplant DSA and BAFF at day 7 into four groups. RESULTS: During the study
      period, 13.2% of the recipients demonstrated subclinical-ABMR at 6 months,
      without patient with clinical ABMR presentations. Overall mean BAFF at day 7 was
      393 pg/mL (95% CI = 316-471 pg/mL). The optimal cut-off value for low vs. high
      BAFF level was 573 pg/mL, with sensitivity and specificity at 77.8% and 88.1%,
      respectively. Fifty percent of recipients with high BAFF at day 7 (14 patients)
      and only 3.7% of patients with low BAFF demonstrated ABMR (P < 0.05). Indeed,
      ABMR was more common in patients high BAFF level (hazard ratio = 7.30; 95% CI =
      3.77-14.15). The prevalence of ABMR among negative pre-transplant DSA/low BAFF,
      positive DSA/low BAFF, negative DSA/high BAFF, and positive DSA/ high BAFF
      recipients were 4.4, 0, 37.5 and 66.7%, respectively (P < 0.05). CONCLUSIONS:
      Post-transplant ABMR can be predicted by perioperative serum BAFF level. Together
      with DSA testing, BAFF provides additional predictive value for ABMR.

PMID- 27888575
TI  - The effect of fibrinogen concentrate on perioperative bleeding in transurethral
      resection of the prostate: a double-blind placebo-controlled and randomized
      study.
AB  - : Essentials Perioperative bleeding during prostate surgery is still a common
      morbidity. Anticoagulant and antiplatelet medications contribute to the risk of
      hemorrhage and prolonged hospital stay. Multiple pharmacological agents have been
      proposed, but none of them have been widely accepted. It is crucial to find a
      safe and effective modality to reduce hemorrhage. SUMMARY: Background Hemorrhage
      during transurethral resection of the prostate (TUR-P) has always been a concern.
      Several studies have shown preoperative administration of fibrinogen concentrate
      to have promising results in reducing hemorrhage in cardiac surgery. Objectives
      To investigate the hemostatic effect of fibrinogen concentrate administration on
      reducing the amount of bleeding during TUR-P in patients with benign prostatic
      hyperplasia. Methods Sixty men with benign prostatic hyperplasia, who were chosen
      to undergo TUR-P, entered this prospective randomized double-blind placebo
      controlled study. The participants were randomly assigned to two groups:
      treatment (n = 31) and placebo (n = 29). They received an infusion of 2 g of
      fibrinogen concentrate (treatment group) or normal saline (placebo group) before
      surgery. Data regarding the amount of bleeding, the operation and complications
      were recorded and analyzed. Results No difference was observed in bleeding
      between the fibrinogen and placebo groups during (521 mL versus 557 mL,
      respectively) and after (291 mL versus 341 mL, respectively) surgery. This lack
      of difference was also seen in operation time (43 min versus 42 min), irrigating
      fluid volume used during (17 L versus 19 L) and after (29 L versus 28 L) surgery,
      and resected adenoma volume (19 g versus 19 g). The mean blood pressure was also
      similar in both groups as a confounding factor for the amount of bleeding.
      Conclusion Preoperative administration of fibrinogen concentrate had no
      significant influence on intraoperative and postoperative bleeding in TUR-P
      surgery.

PMID- 27888574
TI  - Normal 'heart' in Parkinson's disease: is this a distinct clinical phenotype?
AB  - BACKGROUND AND PURPOSE: Reduction of metaiodobenzylguanidine (MIBG) uptake has
      been observed in almost all patients with Parkinson's disease (PD), associated
      with hyposmia, orthostatic hypotension and rapid eye movement sleep behavioral
      disorder (RBD). In contrast, a subgroup of patients with PD with normal MIBG
      uptake have been reported to have milder disease and preserved cognition compared
      with those with lower MIBG. The aim of this study was to investigate whether non
      motor manifestations of PD differ between patients with normal and abnormal
      myocardial MIBG uptake. METHODS: Among 160 de-novo cases of PD, 44 had normal
      MIBG uptake. Twelve candidate non-motor features were evaluated using
      questionnaires and laboratory tests. RESULTS: Patients with decreased MIBG uptake
      had more constipation, RBD, cognitive impairment, hyposmia and orthostatic
      hypotension than did those with normal MIBG uptake. On linear regression
      analysis, orthostatic hypotension, olfactory function and probable RBD were
      significantly associated with MIBG uptake in PD. The principal component analysis
      showed that the group with normal MIBG was not associated with non-motor
      impairments. CONCLUSIONS: These results suggest that patients with PD with normal
      MIBG scans have a relatively low disease burden compared with those with abnormal
      MIBG. Fewer synuclein pathologies in the myocardia and sympathetic ganglia in PD
      with preserved MIBG uptake might be associated with lower threshold patterns of
      Braak synuclein pathology for non-motor manifestations compared with PD with
      decreased MIBG.

PMID- 27888576
TI  - Total Recall: Can We Reshape T Cell Memory by Lymphoablation?
AB  - Despite recent advances in immunosuppression, donor-reactive memory T cells
      remain a serious threat to successful organ transplantation. To alleviate
      damaging effects of preexisting immunologic memory, lymphoablative induction
      therapies are used as part of standard care in sensitized recipients. However,
      accumulating evidence suggests that memory T cells have advantages over their
      naive counterparts in surviving depletion and expanding under lymphopenic
      conditions. This may at least partially explain the inability of existing
      lymphoablative strategies to improve long-term allograft outcome in sensitized
      recipients, despite the well-documented decrease in the frequency of early acute
      rejection episodes. This minireview summarizes the insights gained from both
      experimental and clinical transplantation as to the effects of existing
      lymphoablative strategies on memory T cells and discusses the latest research
      developments aimed at improving the efficacy and safety of lymphoablation.

PMID- 27888577
TI  - Viral ecology comes of age.

PMID- 27888578
TI  - Clinical evaluation of a radio-protective cream for the hands of the pediatric
      interventional cardiologist.
AB  - OBJECTIVES: The aim of this study was to evaluate the effectiveness of
      UltraBLOXTM radiation attenuating hand cream during lengthy cardiac
      catheterization procedures in children. BACKGROUND: The hands of interventional
      cardiologists receive high doses of radiation due to their proximity to the X-ray
      beam. Radiation attenuating gloves have about a 26% attenuation rate, but reduce
      dexterity and tactile sensation. The UltraBLOXTM cream is a new FDA-approved X
      ray attenuating cream that can be applied to the operator's hands for radio
      protection. METHODS: Two nanoDotTM dosimeters were secured side by side on the
      dorsum of the operator's (n = 2) left hand close to the wrist. One dosimeter and
      the rest of the hand were covered with 0.2 mm layer of the cream. The other
      dosimeter was unshielded. Procedures were performed using 110 kVp fluoroscopy at
      15 pulses/sec. The measurements were categorized into four groups dependent on
      the duration of the procedure. The patients in all four groups were well matched
      for age and size. RESULTS: Procedural and cumulative hand radiation doses were
      higher with longer procedural duration. The overall % attenuation by the cream
      was 39.7% (28.6-51.5) and was unaffected by the length of the procedure (median:
      40.9% at 30 min and 41.4% at 180 min; P = 0.66) or the dose of radiation. The
      kappa statistic for interobserver agreement for good tactile sensitivity was
      0.82. CONCLUSIONS: UltraBLOXTM cream provides a new option for radio-protection
      for the hands of interventional cardiologists without impairing tactile
      sensitivity. There was no decrease in attenuation up to 180 min. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27888579
TI  - Non-target effects of fungicides on nectar-inhabiting fungi of almond flowers.
AB  - Nectar mediates interactions between plants and pollinators in natural and
      agricultural systems. Specialized microorganisms are common nectar inhabitants,
      and potentially important mediators of plant-pollinator interactions. However,
      their diversity and role in mediating pollination services in agricultural
      systems are poorly characterized. Moreover, agrochemicals are commonly applied to
      minimize crop damage, but may present ecological consequences for non-target
      organisms. Assessment of ecological risk has tended to focus on beneficial
      macroorganisms such as pollinators, with less attention paid to microorganisms.
      Here, using culture-independent methods, we assess the impact of two widely-used
      fungicides on nectar microbial community structure in the mass-flowering crop
      almond (Prunus dulcis). We predicted that fungicide application would reduce
      fungal richness and diversity, whereas competing bacterial richness would
      increase, benefitting from negative effects on fungi. We found that fungicides
      reduced fungal richness and diversity in exposed flowers, but did not
      significantly affect bacterial richness, diversity, or community composition. The
      relative abundance of Metschnikowia OTUs, nectar specialists that can impact
      pollination, was reduced by both fungicides. Given growing recognition of the
      importance of nectar microorganisms as mediators of plant-pollinator mutualisms,
      future research should consider the impact of management practices on plant
      associated microorganisms and consequences for pollination services in
      agricultural landscapes.

PMID- 27888580
TI  - Biology of VO2 max: looking under the physiology lamp.
AB  - In this review, we argue that several key features of maximal oxygen uptake (VO2
      max) should underpin discussions about the biological and reductionist
      determinants of its interindividual variability: (i) training-induced increases
      in VO2 max are largely facilitated by expansion of red blood cell volume and an
      associated improvement in stroke volume, which also adapts independent of changes
      in red blood cell volume. These general concepts are also informed by cross
      sectional studies in athletes that have very high values for VO2 max. Therefore,
      (ii) variations in VO2 max improvements with exercise training are also likely
      related to variations in these physiological determinants. (iii) All previously
      untrained individuals will respond to endurance exercise training in terms of
      improvements in VO2 max provided the stimulus exceeds a certain volume and/or
      intensity. Thus, genetic analysis and/or reductionist studies performed to
      understand or predict such variations might focus specifically on DNA variants or
      other molecular phenomena of relevance to these physiological pathways.

PMID- 27888581
TI  - Vascular Toxicity Risk Assessment of MC18 and MC70, Novel Potential Diagnostic
      Tools for In Vivo PET Studies.
AB  - The P-glicoprotein (P-gp) inhibitor MC18 has been recently proposed as a valuable
      PET tracer to measure P-gp expression in vivo. The aim of this study was to
      evaluate the toxic hazard towards the vasculature of MC18 along with the
      structurally related and more potent P-gp inhibitor MC70. Their effects on A7r5
      and EA.hy926 cells viability, on the mechanical activity of fresh and cultured
      rat aorta rings as well as on Cav 1.2 channel current (ICa1.2 ) of A7r5 cells
      were studied. At concentrations >10 MUM, MC18 and MC70 decreased cell viability
      causing evident morphological changes. In fresh rat aorta rings, both compounds
      (0.1-100 MUM) antagonized phenylephrine-induced contraction in a concentration
      dependent manner, with IC50 values in the range of 1.67-14.49 MUM, whereas only
      MC18 caused a concentration-dependent decrease of the 60 mM K+ (K60)-induced
      responses. In rings cultured for 7 days with both compounds (1-10 MUM), 10 MUM
      MC70 significantly reduced, while 10 MUM MC18 completely prevented the
      contractile response to both phenylephrine and K60. MC18 and MC70 (0.1-100 MUM)
      inhibited ICa1.2 in a concentration-dependent manner with IC50 values of 16.81
      and 32.13 MUM, respectively. These findings demonstrate that MC18-induced
      vascular effects took place at concentrations that are at least three orders of
      magnitude higher than those (<=10 nM) allowing in vivo measurement of P-gp
      expression. Thus, MC18, and possibly MC70, can be considered promising PET tools
      for in vivo P-gp quantification.

PMID- 27888583
TI  - Systematic Epidemiological Investigations of Cases of Senecavirus A in US Swine
      Breeding Herds.
AB  - Epidemiological investigations were conducted on a case series of six Senecavirus
      A (SVA)-affected breeding herds in the United States to determine potential
      routes of introduction and enhance the swine industry's knowledge of SVA's
      clinical presentation and spread. Each SVA-affected herd was evaluated using a
      standard form to ensure that all relevant data were collected. The form was used
      to guide a detailed discussion about the clinical presentation of SVA and risk
      events that occurred in the 4 weeks prior to the first observation of clinical
      signs with the herd veterinarian and farm personnel. Each event was then
      subjectively assigned a risk level of low, medium or high likelihood for SVA
      introduction by the investigation team. The clinical presentation of SVA varied
      by case. All SVA-affected herds (six of six) reported increases in pre-weaning
      mortality and sow anorexia. Vesicular lesions were observed in four of six herds,
      and mild-to-moderate neonatal diarrhoea was observed in three of six herds. No
      gross anatomic or histologic lesions were observed in neonatal pigs that tested
      positive for SVA via PCR. Multiple potential routes of introduction were
      identified. Events subjectively rated as high risk for SVA introduction were on
      farm employee entry (six of six), carcass disposal (four of six), cull sow
      removal (three of six) and breeding replacement entry (two of six). Non-swine
      domestic animals, rodents, other visitors, repairs outside swine barns, feed
      delivery, weaned pig removal and semen entry were assigned a high risk level in
      one of six herds. Cases occurred in breeding herds of all sizes with variable
      biosecurity in both swine dense and swine sparse areas.

PMID- 27888584
TI  - Small Molecule Inhibiting Nuclear Factor-kB Ameliorates Oxidative Stress and
      Suppresses Renal Inflammation in Early Stage of Alloxan-Induced Diabetic
      Nephropathy in Rat.
AB  - Diabetic nephropathy is one of the major microvascular complications of diabetes
      mellitus which ultimately gives rise to cardiovascular diseases. Prolonged
      hyperglycaemia and chronic renal inflammation are the two key players in the
      development and progression of diabetic nephropathy. Nuclear factor kB (NF-kB)
      mediated inflammatory cascade is a strong contributor to the renovascular
      inflammation in diabetic nephropathy. Here, we studied the effects of
      piceatannol, a potent NF-kB inhibitor, on various oxidative stress markers and NF
      kB dependent diabetic renoinflammatory cascades in rat induced by alloxan (ALX).
      Experimental diabetes was induced in male Wistar rats by a single intraperitoneal
      dose, 150 mg/kg body-weight (b.w.) of ALX. Diabetic rats were treated with
      Piceatannol (PCTNL) at a dose of 30 and 50 mg/kg b.w. After 14 days of oral
      treatment, PCTNL significantly restored blood sugar level, glomerular filtration
      rate, serum markers and plasma lipids. PCTNL administration also reversed the
      declined activity of cellular antioxidant machineries namely superoxide dismutase
      and glutathione and the elevated levels of malondialdehyde and nitric oxide.
      Moreover, piceatannol-treated groups showed marked inhibition of renal pro
      inflammatory cytokines and NF-kB p65/p50 binding to DNA. Renal histopathological
      investigations also supported its ameliorative effects against diabetic kidney
      damage. Importantly, effects were more prominent at a dose of 50 mg/kg, and in
      terms of body-weight gain, PCTNL failed to effect significantly. However, overall
      findings clearly demonstrated that PCTNL provides remarkable renoprotection in
      diabetes by abrogating oxidative stress and NF-kB activation - and might be
      helpful in early stage of diabetic nephropathy.

PMID- 27888582
TI  - Nucleotide substitutions in CD101, the human homolog of a diabetes susceptibility
      gene in non-obese diabetic mouse, in patients with type 1 diabetes.
AB  - AIMS/INTRODUCTION: Although genome-wide association studies have identified more
      than 50 susceptibility genes for type 1 diabetes, low-frequency risk variants
      could remain unrecognized. The present study aimed to identify novel type 1
      diabetes susceptibility genes by newly established methods. MATERIALS AND
      METHODS: We carried out whole-exome sequencing and genome-wide copy-number
      analysis for a Japanese family consisting of two patients with type 1 diabetes
      and three unaffected relatives. Further mutation screening was carried out for
      127 sporadic cases. The functional consequences of identified substitutions were
      evaluated by in silico analyses and fluorescence-activated cell sorting of blood
      samples. RESULTS: Whole-exome sequencing and genome-wide copy-number analysis of
      familial cases showed co-segregation of the p.V863L substitution in CD101, the
      human homolog of an autoimmune diabetes gene in the non-obese diabetic mouse,
      with type 1 diabetes. Mutation screening of CD101 in 127 sporadic cases detected
      the p.V678L and p.T944R substitutions in two patients. The p.V863L, p.V678L and
      p.T944R substitutions were absent or extremely rare in the general population,
      and were assessed as 'probably/possibly damaging' by in silico analyses. CD101
      expression on monocytes, granulocytes and myeloid dendritic cells of mutation
      positive patients was weaker than that of control individuals. CONCLUSIONS: These
      results raise the possibility that CD101 is a susceptibility gene for type 1
      diabetes.

PMID- 27888585
TI  - Discrepancy rates in reporting of acute stroke CT.
AB  - INTRODUCTION: With increasing after-hours workloads there has been reliance on
      registrars to report after-hours acute stroke CT scans at our institution. This
      practice was reviewed for the perceived possibility of error and poor patient
      outcomes by the reliance on after-hours registrar reports. Through an audit of 3
      years of these studies, we proposed to investigate if our current practice is
      safe and whether it results in poor patient outcomes. METHODS: Following ethics
      approval, all after-hours acute stroke CT scan reports from September 2012 to
      August 2015 were identified using the PACS. All reports were reviewed with data
      recorded on a written worksheet then transferred to an Excel spreadsheet for
      analysis. The consultant report was used as the gold standard. In cases where
      discrepancies occurred, medical records were reviewed. RESULTS: Eight hundred and
      ninety-four acute stroke CT scans were identified in the audit period with a
      subset of 316 studies identified where a registrar report was issued at time of
      scan and checked the following day by a radiology consultant. There were 114
      discrepancies (10 were major, 51 were minor, and 53 other). In three discrepancy
      cases, the patient's clinical course was altered. There were no adverse outcomes
      as a result of a discrepancy. Using a radiology consultant as the gold standard
      the major discrepancy rate was ~3% in the after-hours setting. CONCLUSION: Our 3
      year retrospective audit demonstrates that our practice of registrar report
      issued at the time of CT scan checked the following day by a radiologist has a
      low major discrepancy rate and that patient safety was not compromised. These
      results support the continuation of our current practice.

PMID- 27888586
TI  - Sequence and Phylogenetic Analyses of the Nsp2 and ORF5 Genes of Porcine
      Reproductive and Respiratory Syndrome Virus in Boars from South China in 2015.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is highly genetically
      diverse; however, little is known about the molecular epidemiology of PRRSV in
      the boar farms of South China. In this study, 367 samples were collected from
      boar farms in South China in 2015. The Nsp2 hypervariable region and ORF5 gene
      were PCR amplified from 66 PRRSV-positive samples, followed by sequencing and
      analysis. The percentage of PRRSV antigen-positive samples was 17.98%; 8.72% were
      positive for highly pathogenic PRRSV (HP-PRRSV), and 9.26% were positive for low
      pathogenic PRRSV (LP-PRRSV). Sequence alignment and phylogenetic tree analyses
      revealed three novel patterns of deletion in the hypervariable region of Nsp2,
      which had not been identified previously. Furthermore, numerous amino acid
      substitutions were identified in the putative signal peptide and extravirion
      regions of GP5. These results demonstrate for the first time that the existence
      of multiple different strains on the same boar farm, and extensive genetic
      mutation and high infection rate of PRRSV in boars from South China. Our research
      contributes to the understanding of the epidemiology and genetic characteristics
      of PRRSV on boar farms.

PMID- 27888587
TI  - Tuberculosis Caused by Mycobacterium orygis in Dairy Cattle and Captured Monkeys
      in Bangladesh: a New Scenario of Tuberculosis in South Asia.
AB  - Mycobacterium orygis, commonly known as the oryx bacillus and a newly proposed
      Mycobacterium tuberculosis complex subspecies, was isolated from 18 cattle in a
      dairy farm and two captured rhesus monkeys in a zoo in Bangladesh. All the
      infected animals had tuberculosis lesions in their lungs, suggesting transmission
      and infection with M. orygis by an airborne route. The 20 isolates were analysed
      using a range of conventional and molecular typing methods, and RD-deletion
      typing and sequencing of selected genes confirmed the isolates as M. orygis.
      Multiple-locus variable-number tandem repeat analysis (MLVA) allowed the isolates
      to be divided into three clusters based on the relatedness of their MLVA
      profiles. The two monkey isolates shared the same MLVA pattern with 15 of the
      cattle isolates, whereas the remaining three cattle isolates had different
      patterns, even though the latter animals had been kept in the same dairy farm.
      The diversity observed among isolates may suggest the bacteria have been
      established in this area for a long period. This study along with other recent
      findings that report the detection of M. orygis from animals as well as humans
      originating from South Asia potentially indicate endemic distribution of M.
      orygis in South Asia.

PMID- 27888588
TI  - LPS-Responsive Beige-Like Anchor Gene Mutation Associated With Possible
      Bronchiolitis Obliterans Organizing Pneumonia Associated With
      Hypogammaglobulinemia and Normal IgM Phenotype and Low Number of B Cells.
AB  - LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has
      recently been described in a group of patients with common variable
      immunodeficiency (CVID) in association with autoimmunity and/or inflammatory
      bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who
      experienced recurrent infections, mainly in the respiratory system, associated
      with thrombocytopenia and anemia. Immunological workup showed low numbers of B
      cells and low IgG, but normal IgM levels. In spite of therapeutic doses of
      antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin
      replacement therapy, he developed disseminated involvement of both lungs with
      peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis
      obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome
      sequencing identified a homozygous LRBA mutation in this patient
      (p.Asp248Glufs*2). Such clinical and immunological findings have not been
      described to date and illustrate the broad and variable clinical phenotype of
      human LRBA deficiency.

PMID- 27888589
TI  - Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia
      Reperfusion-Induced Renal Injury in Rats.
AB  - Renal ischemia-reperfusion (IR) contributes to the development of acute renal
      failure (ARF). Oxygen free radicals are considered to be principal components
      involved in the pathophysiological tissue alterations observed during renal IR.
      The purpose of this study was to investigate the combination effect of melatonin
      (MEL) and erythropoietin (EPO), which are a potent antioxidant and anti-apoptotic
      agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally
      nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24
      h reperfusion. MEL (10 mg/kg, i.p) and EPO (5000 U/kg, i.p) were administered
      prior to ischemia. After 24 h reperfusion, following decapitation, blood samples
      were collected for the determination of superoxide dismutase (SOD), glutathione
      peroxidase (GPx), and malondialdehyde (MDA) levels. Also, renal samples were
      taken for histological evaluation and apoptosis assay. Ischemia-reperfusion
      increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological
      findings of the IR group confirmed that there was renal impairment in the tubular
      epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels,
      histopathological changes, and TUNEL positive cells. These results indicated that
      the combination of MEL and EPO could not exert more nephroprotective and anti
      apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

PMID- 27888590
TI  - Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl4-Induced
      Cirrhotic Rats: The Ameliorative Effect of Naltrexone.
AB  - Cirrhosis is the consequence of chronic liver disease. Deleterious effects of
      oxidative stress on hepatocytes may be reflected in the erythrocyte membrane.
      Naltrexone (NTX) has been shown to attenuate hepatocellular injury in fibrotic
      animal models. The aim of this study was to investigate the progressive effect of
      CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored
      through alterations in the erythrocyte membrane. In this study, 84 male Wistar
      rats were divided into 4 groups and received reagents (i.p.) as follows: 1- CCl4,
      2- NTX + CCl4, 3- Mineral Oil (M), and 4- NTX + M. After 2, 6 and 8 weeks, the
      blood and liver tissue samples were collected. Plasma enzyme activities, the
      content of erythrocyte GSH and some membrane compositions, including protein
      carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8
      weeks, plasma enzyme activities and the content of protein carbonyl were higher
      in CCl4 group significantly, as compared to other groups (P<0.001). NTX
      significantly diminished protein carbonyl and plasma enzyme activities (P<0.001).
      GSH did not change until the 6th week. However, CCl4+NTX increased it
      significantly as compared to CCl4 group (P<0.05). Protein sulfhydryl showed
      changes in NTX+CCl4 group which indicated a significant increase in protein
      sulfhydryl content in a 6th week compared to CCl4 group (P<0.05). MDA did not
      show any significant alteration. CCl4-induced cirrhosis is accompanied by
      increased content of oxidative stress markers, especially protein carbonyl of RBC
      membrane and plasma enzyme activities. This study shows that the progression of
      liver cirrhosis and the ameliorative effect of NTX can be followed through
      alterations of these markers.

PMID- 27888591
TI  - A Novel Approach to Minimally Invasive Management of Sigmoid Volvulus.
AB  - Resection is the most common treatment choice for sigmoid volvulus, a common
      complication in our region. A new minimally invasive technique for sigmoid
      resection with local anesthesia was done in this study. This method is invented
      to avoid general on regional anesthesia in high-risk patients. Nineteen patients
      were evaluated and then 14 were enrolled in this study. Sigmoidectomy with a left
      lower quadrant incision was performed and demographic data, the length of
      hospital stay, complications and procedure time were recorded. The mean age of
      participants was 65.68, and the male to female ratio was 1:2.7. The mean duration
      of the operation was 91.42 min. Complications include one case each of wound
      hematoma and wound infection. The intraoperative pain score was 1.2/10 and
      postoperative pain score was 2.35/10. The mean hospital staying was 8.3 days. By
      meticulous patient selection, sigmoidectomy under local anesthesia for sigmoid
      volvulus could be a surgeons' armamentarium in special situations.

PMID- 27888592
TI  - Problems in Diagnosis and Treatment of Retrorectal Tumors: Our Experience in 50
      Patients.
AB  - Retrorectal tumors are rare lesions in adults, which remains a difficult
      diagnostic and management problem. The purpose of this study was to evaluate the
      results of surgical management of retrorectal tumors in our institution. In a
      retrospective study, a consecutive series of patients who underwent surgical
      excision of a retrorectal tumor were identified from a database. Medical records,
      radiology, pathology reports and surgical approach were checked retrospectively.
      The data was analyzed using SPSS statistical software (version 18). From 50
      patients, 24 were male, and 26 were female with the mean age of 41.7 years. The
      origin of mass was congenital in 46% (23 cases) and neurogenic in 14% (7
      patients), bone origin in 12% (6 cases) and miscellaneous in 24% (12 cases). In
      total, 56.7% (21 cases) were malignant. Surgical approaches included laparotomy
      in 11 cases, the sacral approach in 17 cases, the anterior-posterior approach in
      14 cases and one case through abdomino-sacral approach. The mean follow-up was
      56.7 (10-277) month. Ten patients died due to extensive metastases with a mean
      survival of 46.6 (1-158) months. Primary urethrorectal tumors are very rare.
      Successful treatment of these tumors requires careful clinical evaluation and
      expertise in pelvic surgery.

PMID- 27888593
TI  - A Comparative Study on Dietary Style and Physical Activity of Women With and
      Without Gestational Diabetes.
AB  - Gestational diabetes increases the risks for mother and fetus during pregnancy.
      As a principle of caring for diabetes, recommending patients to lose weight
      through more physical activities and a restrictive diet has a long history. The
      present study was carried out aiming at determining and comparing dietary style
      and physical activity in women with gestational diabetes and healthy pregnant
      women. This descriptive-comparative study was carried out simultaneously on 200
      pregnant women (with gestational diabetes and healthy). Tools for data collection
      were questionnaires of dietary style and physical activity during pregnancy.
      After obtaining research informed consent from samples, sampling was done by
      multi-stage convenience random sampling. Data was analyzed using SPSS 21. The
      results of the study revealed that the demographic and obstetric variables were
      identical. The mean scores for the dietary style of case and control groups were
      65.05 and 74.12, P<0.001 respectively. The mean scores for physical activity
      (inactive cases) in the two groups were 5.64 and 4.70, P<0.223, the mean scores
      for light activity in the two groups were 9.07 and 10.75 (P<0.059), and the mean
      scores for moderate activity in the two groups were 4.62 and 5.69, (P<0.042)
      respectively. Lower status of nutrition and physical activity of women with
      gestational diabetes comparing to non-diabetic pregnant women suggests a need
      providing sufficient and accurate information on appropriate dietary and physical
      activities during pregnancy.

PMID- 27888594
TI  - Effect of Acute Noise Exposure on Salivary Cortisol: A Randomized Controlled
      Trial.
AB  - Cardiovascular adverse effects are interesting aspects of occupational noise
      exposure. One possible mechanism of these effects is an alternation in
      hypothalamic-pituitary-adrenal axis. Our aim was to measure salivary cortisol
      response to relatively high-intensity noise exposure in a controlled randomized
      trial study. We exposed 50 male volunteers to 90 dBA noise for 20 minutes and
      compared their level of salivary cortisol with 50 non-exposed controls. Salivary
      samples obtained before and after exposure. Before intervention means (SD)
      salivary cortisol level were 3.24 (0.47)ng/ml and 3.25 (0.41)ng/ml for exposed
      and non-exposed groups respectively. Mean salivary cortisol level increased to
      4.17 ng/mlafter intervention in exposure group. This increment was statistically
      significant (P=0.00). Mean salivary cortisol level of the non-exposed group had
      statistically non-significant decrement after this period (0.2 ng/ml). The
      difference between salivary cortisol level of non-exposed and exposed groups
      after the intervention was statistically significant. Noise exposure may affect
      the hypothalamic-pituitary-adrenal axis activity, and this may be one of the
      mechanisms of noise exposure cardiovascular effects.

PMID- 27888595
TI  - Quality of Life in Medical Students With Internet Addiction.
AB  - The widespread use of internet has caused new psychological, social, and
      educational problems for the students. The aim of this study was to examine the
      quality of life in medical students who suffer from internet addiction. This
      cross-sectional survey was carried out in Tehran University of Medical Sciences,
      and a total of 174 fourth-to seventh-year undergraduate medical students were
      enrolled. The quality of life was assessed by WHOQOL-BREF questionnaire which
      covers four domains of physical health, psychological, social relationships, and
      the environment. For assessing internet addiction, we used Internet Addiction
      Test (IAT) of Young. The students with IAT score higher than 50 were considered
      as addicted. For evaluating academic performance, the students were requested to
      report their grade point average (GPA). The mean IA score (+/-SD) was 34.13+/
      12.76. Twenty-eight students (16.90%) had IAT score above 50. The mean quality of
      life score in internet addicted group was 54.97+/-11.38 versus 61.65+/-11.21 in
      normal group (P=0.005). Furthermore, there was a negative correlation between IA
      score and physical domain (r=-0.18, P=0.02); psychological domain (r=-0.35,
      P=0.000); and social relation domain (r=-0.26, P=0.001). Mean GPA was
      significantly lower in the addicted group. It seems that quality of life is lower
      in the internet addicted medical students; moreover, such students academically
      perform poorer in comparison with non-addicts. Since internet addiction is
      increasing at a rapid pace which may provoke considerable academic, psychological
      and social implications; as a result, it may require screening programs to the
      immediate finding of such problem to give consultations to prevent unwanted
      complications.

PMID- 27888596
TI  - A Study of the Readiness of Hospitals for Implementation of High Reliability
      Organizations Model in Tehran University of Medical Sciences.
AB  - Creating a safe of health care system requires the establishment of High
      Reliability Organizations (HROs), which reduces errors, and increases the level
      of safety in hospitals. This model focuses on improving reliability through
      higher process design, building a culture of accreditation, and leveraging human
      factors. The present study intends to determine the readiness of hospitals for
      the establishment of HROs model in Tehran University of Medical Sciences from the
      viewpoint of managers of these hospitals. This is a descriptive-analytical study
      carried out in 2013-2014. The research population consists of 105 senior and
      middle managers of 15 hospitals of Tehran University of Medical Sciences. The
      data collection tool was a 55-question researcher-made questionnaire, included
      six elements of HROs to assess the level of readiness for establishing HROS model
      from managers' point of view. The validity of the questionnaire was calculated
      through the content validity method using 10 experts in the area of hospitals'
      accreditation, and its reliability was calculated through test-retest method with
      a correlation coefficient of 0.90. The response rate was 90 percent. The Likert
      scale was used for the questions, and data analysis was conducted through SPSS
      version 21 Descriptive statistics was presented via tables and normal
      distributions of data and means. Analytical methods, including t-test, Mann
      Whitney, Spearman, and Kruskal-Wallis, were used for presenting inferential
      statistics. The study showed that from the viewpoint of senior and middle
      managers of the hospitals considered in this study, these hospitals are indeed
      ready for acceptance and establishment of HROs model. A significant relationship
      was showed between HROs model and its elements with demographic details of
      managers like their age, work experience, management experience, and level of
      management. Although the studied hospitals, as viewed by their managers, are
      capable of attaining the goals of HROs, it seems there are a lot of challenges in
      this way. Therefore, it is suggested that a detailed audit is conducted among
      hospitals' current status regarding different characteristics of HROs, and
      workshops are held for medical and non-medical employees and managers of
      hospitals as an influencing factor; and a re-assessment process afterward, can
      help moving the hospitals from their current position towards an HROs culture.

PMID- 27888597
TI  - Team-Based Learning: A New Approach Toward Improving Education.
AB  - Team-based learning is designed to provide students with both conceptual and
      procedural knowledge, aiming to enhance active learning and critical thinking. In
      the present study, team-based learning and lecture methods in teaching the
      "hospital organization and management" course among hospital management students
      were compared. This quasi-experimental study was conducted on 25 undergraduate
      students of management. Teaching sessions were divided into two parts. The first
      part was taught with interactive lectures and the second part with team-based
      learning method. The students' knowledge was measured before, immediately and two
      months (late post-test) after teaching. Finally, the mean scores of the final
      exam and students' satisfaction towards the methods of teaching were measured.
      There was an improvement in test scores of the students after the TBL sessions
      when compared to the test scores after lecture sessions (P<0.001). Also, TBL
      group had significantly a higher amount of knowledge retention compared to the
      lecture group (P<0.001), but no significant relationship was found between the
      mean scores of the final exam in the TBL and lecture groups (P=0.116). Finally,
      the majority of the respondents were more satisfied with TBL sessions compared to
      the ones held through lecture (P=0.037). The results indicated that TBL provides
      a better outcome for students. We found that the TBL approach allowed us to
      create an active learning environment that contributed to the improvement of the
      students' performances.

PMID- 27888598
TI  - Adult Onset Still's Disease With Different Antibodies: A Case Report and Review
      of Literature.
AB  - Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of
      unknown etiology. There is not currently any specific serological markers for
      AOSD , and  diagnosis still relying on the exclusion of other likely diagnoses.
      Yamaguchi's criteria are used as a diagnostic criterion which contains negative
      serologic markers for other collagen vascular diseases including systemic lupus
      erythematosus and rheumatoid arthritis. Here we report a 28-year-old woman with
      arthralgia, fever, rash, leukocytosis, lymphadenopathy, sore throat, abnormal
      liver function and negative rheumatoid factor and ANA but  seropositive for anti
      CCP, anti-dsDNA, and C-ANCA. It seems that despite AOSD is considered as a
      seronegativedisorder; it should be remembered in patients with compatible
      findings who are seropositive.

PMID- 27888599
TI  - A Rare Anomaly of Duodenum: A Case Report.
AB  - Anatomical variations of duodenum such as atresia, stenosis, and variations in
      shape have been described by various authors, but the existence of a gross
      anomaly in shape and position of midgut segment of the duodenum is rare. Few
      reported cases of duodenal anomalies date back to early twentieth century. In the
      wake of advancement of imaging techniques and minimal access surgeries, authors
      report a case of a rare duodenal anomaly. The reported case assumes significance
      because of thepossibility of misinterpretation of radiological images which has
      been discussed while citing such references. The present case reports an anomaly
      of the position of the midgut segment of the duodenum in an adult female cadaver.
      It was observed that the lower half of second part of duodenum was coiled like a
      serpent on the upper pole of right kidney. This part coursed initially upwards
      running parallel and to the right of the upper half of the second part of the
      duodenum. The third part coursed downwards and to the left, posterior to head and
      neck of pancreas, in its course sandwiching the commencement of portal vein.

PMID- 27888600
TI  - [Darunavir/cobicistat monotherapy. Experience in a tertiary hospital].
AB  - OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy:
      darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only
      provided in the major treatment guidelines in pretreated patients to prevent
      toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor
      (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r
      monotherapy, according to GESIDA guidelines 2016, patients need to meet the
      following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/
      mL for at least 6 months and absence of protease inhibitors mutations or previous
      virologic failures to IP/r. Currently, there are no studies that evaluate the
      efficacy and safety of darunavir/cobicistat (DRV/COBI) monotherapy. METHODS: This
      prospective study analyzed pretreated HIV patients with DRV/r monotherapy that
      were switched to DRV/COBI monotherapy. The aim of the study is to describe the
      effectiveness and safety of the DRV/COBI monotherapy. RESULTS: Seventy-eight
      patients were evaluated. Patients had a median of 31.29 months of DRV/r
      monotherapy before DRV/COBI monotherapy. Nine of the 78 patients developed
      "blips" (plasma viral load: 50-200 copies/ml) and four patients had plasma viral
      load >=200 copies/mL. An 83.3% (65/78) of the patients remained with undetectable
      plasma viral load. As for safety, there were no significant differences in lipid
      profile, liver function (transaminases) and renal function between DRV/r and
      DRV/COBI monotherapy. CONCLUSIONS: DRV/COBI monotherapy seems to be effective and
      safe (lipid profile, liver and kidney function). However, it will be necessary to
      design specific studies comparing DRV/r vs DRV/COBI monotherapy to confirm these
      results.

PMID- 27888601
TI  - Key issues in the infected patient care in the Emergency Department.
AB  - OBJECTIVE: To develop a set of recommendations, by consensus of Emergency
      Medicine experts, on key aspects related to the care of adult patients with acute
      infection attended in Spanish emergency departments (ED). METHODS: The study was
      divided into three phases: 1) To design a questionnaire by a coordinating group;
      2) To conduct a survey in ED physicians in order to know their opinion on the
      issues raised by the coordinating group; 3) To develop a number of
      recommendations based on the responses to the questionnaire and their subsequent
      discussion. RESULTS: A group of 28 experts from different Spanish ED, as well as
      5 members of the coordinating group, with knowledge and experience in the
      management of infectious diseases in ED, conducted a round of voting to a
      questionnaire of 18 issues grouped into three sections: 1) identification and
      stratification of the severity; 2) diagnosis and treatment; 3) management.
      CONCLUSIONS: A monitoring system and proper training of the entire healthcare
      team are required, as well as extensive knowledge on these issues, to ensure
      adequate and effective care for these patients. It is essential to educate and
      train all health staff, especially in the ED, because it is the initial point of
      contact for most patients with an infection. The experts established proposals
      based on survey questions and the discussion.

PMID- 27888603
TI  - Development of a mechanical sexing system to improve the efficacy of an area-wide
      sterile insect release programme to control American serpentine leafminer
      (Diptera: Agromyzidae) in Canadian ornamental greenhouses.
AB  - BACKGROUND: American serpentine leafminer (ASL), Liriomyza trifolii (Burgess), is
      a significant pest of greenhouse ornamental crops, and females damage leaf tissue
      with their ovipositor during feeding and oviposition. The sterile insect
      technique has been advocated as a non-chemical alternative to currently available
      control methods. In area-wide sterile insect release programmes, males act as
      true vectors of sterility. Females should be eliminated from a cohort of pupae
      prior to irradiation to maximise production economics and sterility spread. The
      aim of this research was to develop a mechanical sexing system based on pupal
      size to reduce the proportion of ASL females. RESULTS: Cumulative frequency
      distributions were used to examine significant differences in male and female
      pupal length and dorsal and lateral width distributions. Optimum size cut-off
      points based on the largest differences in distribution curves were used to
      determine the dimensions of three different sieve designs. Sieve pores measuring
      1.543 mm by 0.765 mm excluded 76% of female pupae and doubled the proportion of
      males in the throughput sample. CONCLUSION: Pupal sexual dimorphisms identified
      in this research can be used to design a sieve to aid in reducing the proportion
      of females prior to irradiation, thus improving the efficacy of an area-wide
      sterile insect release programme. (c) 2016 Society of Chemical Industry.

PMID- 27888602
TI  - A Glycovariant of Human CD44 is Characteristically Expressed on Human Mesenchymal
      Stem Cells.
AB  - The clinical effectiveness of systemically administered human mesenchymal stem
      cells (hMSCs) depends on their capacity to engage vascular endothelium. hMSCs
      derived from bone marrow (BM-hMSCs) natively lack endothelial binding capacity,
      but express a CD44 glycovariant containing N-linked sialyllactosamines that can
      be alpha(1,3)-fucosylated using fucosyltransferase-VI (FTVI) to enforce sLeX
      decorations, thereby creating hematopoietic cell E-/L-selectin ligand (HCELL).
      HCELL expression programs potent shear-resistant adhesion of circulating cells to
      endothelial beds expressing E-selectin. An alternative source of hMSCs is adipose
      tissue (A-hMSCs), and we assessed whether A-hMSCs bind E-selectin and/or possess
      sialyllactosamine-decorated CD44 accessible to alpha(1,3)-fucosylation. Similar
      to BM-hMSCs, we found that A-hMSCs natively lack E-selectin ligands, but FTVI
      mediated cell surface alpha(1,3)-fucosylation induces sLeX expression and robust
      E-selectin binding secondary to conversion of CD44 into HCELL. Moreover,
      treatment with the alpha(1,3)-fucosyltransferase-FTVII also generated expression
      of HCELL on both BM-hMSCs and A-hMSCs, with sLeX decorations created on N-linked
      glycans of the "standard" CD44 (CD44s) isoform. The finding that hMSCs from both
      source tissues each lack native E-selectin ligand expression prompted examination
      of the expression of glycosyltransferases that direct lactosaminyl glycan
      synthesis. These studies reveal that both types of hMSCs conspicuously lack
      transcripts encoding alpha(1,3)-fucosyltransferases, but equally express
      glycosyltransferases critical to creation of sialyllactosamines. Collectively,
      these data indicate that assembly of a sialyllactosaminyl-decorated CD44s
      glycovariant is a conserved feature of hMSCs derived from adipose tissue and
      marrow, thus identifying a CD44 glycosignature of these cells and supporting the
      applicability of cell surface alpha(1,3)-fucosylation in programming migration of
      systemically administered A-hMSCs to sites of tissue injury/inflammation. Stem
      Cells 2017;35:1080-1092.

PMID- 27888604
TI  - MRI depiction and 3D visualization of three anterior cruciate ligament bundles.
AB  - The anterior cruciate ligament (ACL) is divided into three fiber bundles (AM-M:
      anteromedial-medial, AM-L: anteromedial-lateral, PL: posterolateral). We
      attempted to depict the three bundles of the human ACL on MRI images and to
      obtain 3-dimensional visualization of them. Twenty-four knees of healthy
      volunteers (14 males, 10 females) were scanned by 3T-MRI using the fat
      suppression 3D coherent oscillatory state acquisition for the manipulation of
      imaging contrast (FS 3D-COSMIC). The scanned images were reconstructed after the
      isotropic voxel data, which allows the images to be reconstructed in any plane,
      was acquired. We conducted statistical examination on the identification rate of
      the three ACL bundles by 2D planes. Segmentation and 3D visualization of the
      fiber bundles using volume rendering were performed. The triple-bundle ACL was
      best depicted in the oblique axial plane. While the AM-M and AM-L bundles were
      clearly depicted in all cases, the PL bundle was not clearly visualized in two
      knees (8%). Therefore, the three ACL bundles were depicted in 22 knees (92%). The
      results of 3D visualization of the fiber arrangement agreed well with macroscopic
      findings of previous anatomical studies. 3T-MRI and the isotropic voxel data from
      FS 3D-COSMIC made it possible to demonstrate the identifiable depiction of three
      ACL bundles in nearly all cases. 3D visualization of the bundles could be a
      useful tool to understand the ACL fiber arrangement. Clin. Anat. 30:276-283,
      2017. 2016 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on
      behalf of American Association of Clinical Anatomists.

PMID- 27888605
TI  - Natural antisense transcripts are linked to the modulation of mitochondrial
      function and teliospore dormancy in Ustilago maydis.
AB  - The basidiomycete smut fungus Ustilago maydis causes common smut of corn. This
      disease is spread through the production of teliospores, which are thick-walled
      dormant structures characterized by low rates of respiration and metabolism.
      Teliospores are formed when the fungus grows within the plant, and the
      morphological steps involved in their formation have been described, but the
      molecular events leading to dormancy are not known. In U. maydis, natural
      antisense transcripts (NATs) can function to alter gene expression and many NATs
      have increased levels in the teliospore. One such NAT is as-ssm1 which is
      complementary to the gene for the mitochondrial seryl-tRNA synthetase (ssm1), an
      enzyme important to mitochondrial function. The disruption of ssm1 leads to cell
      lysis, indicating it is also essential for cellular viability. To assess the
      function of as-ssm1, it was ectopically expressed in haploid cells, where it is
      not normally present. This expression led to reductions in growth rate,
      virulence, mitochondrial membrane potential and oxygen consumption. It also
      resulted in the formation of as-ssm1/ssm1 double-stranded RNA and increased ssm1
      transcript levels, but no change in Ssm1 protein levels was detected. Together,
      these findings suggest a role for as-ssm1 in facilitating teliospore dormancy
      through dsRNA formation and reduction of mitochondrial function.

PMID- 27888606
TI  - Discovery of metabolic resistance to neonicotinoids in green peach aphids (Myzus
      persicae) in Australia.
AB  - BACKGROUND: Myzus persicae is a serious pest that attacks a broad range of
      agricultural crops. This species has developed chemical resistance to many
      insecticides globally, and within Australia resistance to multiple chemical
      groups has been identified. Resistance to neonicotinoid insecticides has been
      discovered in several countries, but has not previously been confirmed in
      Australia. We use biomolecular assays and bioassays on field-collected
      populations to investigate neonicotinoid resistance in M. persicae within
      Australia. RESULTS: Several geographically and genetically distinct populations
      showed evidence for resistance in bioassays. Genetic markers identified that the
      mechanism of neonicotinoid resistance in Australia is metabolic resistance
      through the enhanced expression of a cytochrome P450 gene, CYP6CY3. CONCLUSION:
      M. persicae populations in parts of Australia are now resistant to four different
      insecticide chemical groups, raising concerns about the long-term management of
      this pest. While higher copy numbers of CYP6CY3 were seen in all resistant
      populations, the number of gene copies was not strongly correlated with the level
      of resistance as determined by LD50 values generated through bioassays. This
      finding sheds further light on the complexity of the P450 genes in regulating
      neonicotinoid resistance. (c) 2016 Society of Chemical Industry.

PMID- 27888607
TI  - Catastrophic cellular events leading to complex chromosomal rearrangements in the
      germline.
AB  - Although complex chromosomal rearrangements were thought to reflect the
      accumulation of DNA damage over time, recent studies have shown that such
      rearrangements frequently arise from 'all-at-once' catastrophic cellular events.
      These events, designated chromothripsis, chromoanasynthesis, and
      chromoanagenesis, were first documented in the cancer genome and subsequently
      observed in the germline. These events likely result from micronucleus-mediated
      chromosomal shattering and subsequent random reassembly of DNA fragments,
      although several other mechanisms have also been proposed. Typically, only one or
      a few chromosomes of paternal origin are affected per event. These events can
      produce intrachromosomal deletions, duplications, inversions, and translocations,
      as well as interchromosomal translocations. Germline complex rearrangements of
      autosomes often result in developmental delay and dysmorphic features, whereas X
      chromosomal rearrangements are usually associated with relatively mild clinical
      manifestations. The concept of these catastrophic events provides novel insights
      into the etiology of human genomic disorders. This review introduces the
      molecular characteristics and phenotypic outcomes of catastrophic cellular events
      in the germline.

PMID- 27888608
TI  - Efficacy and safety of combined intraventricular fibrinolysis with lumbar
      drainage for prevention of permanent shunt dependency after intracerebral
      hemorrhage with severe ventricular involvement: A randomized trial and individual
      patient data meta-analysis.
AB  - OBJECTIVE: Intraventricular hemorrhage (IVH) is a negative prognostic factor in
      intracerebral hemorrhage (ICH) and is associated with permanent shunt dependency
      in a substantial proportion of patients post-ICH. IVH treatment by
      intraventricular fibrinolysis (IVF) was recently linked to reduced mortality
      rates in the CLEAR III study and IVF represents a safe and effective strategy to
      hasten clot resolution that may reduce shunt rates. Additionally, promising
      results from observational studies reported reductions in shunt dependency for a
      combined treatment approach of IVF plus lumbar drains (LDs). The present
      randomized, controlled trial investigated efficacy and safety of a combined
      strategy-IVF plus LD versus IVF alone-on shunt dependency in patients with ICH
      and severe IVH. METHODS: This randomized, open-label, parallel-group study
      included patients aged 18 to 85 years, prehospital modified Rankin Scale <=3, ICH
      volume < 60ml, Glasgow Coma Scale of <9, and severe IVH with tamponade of the
      third and fourth ventricles requiring placement of external ventricular drainage
      (EVD). Over a 3-year recruitment period, patients were allocated to either
      standard treatment (control group receiving IVF consisting of 1mg of recombinant
      human tissue plasminogen activator every 8 hours until clot clearance of third
      and fourth ventricles) or a combined treatment approach of IVF and-upon clot
      clearance of third and fourth ventricles-subsequent placement of an LD for
      drainage of cerebrospinal fluid (CSF; intervention group). The primary endpoint
      consisted of permanent shunt placement indicated after a total of three
      unsuccessful EVD clamping attempts or need for CSF drainage longer than 14 days
      in both groups. Secondary endpoints included IVF- and LD-related safety, such as
      bleeding or infections, and functional outcome at 90 and 180 days. Conducted
      endpoint analyses used individual patient data meta-analyses. The study was
      registered at clinicaltrials.gov (NCT01041950). RESULTS: The trial was stopped
      upon predefined interim analysis after 30 patients because of significant
      efficacy of tested intervention. The primary endpoint was analyzed without
      dropouts and was reached in 43% (7 of 16) of the control group versus 0% (0 of
      14) of the intervention group (p = 0.007). Meta-analyses were based on overall 97
      patients, 45 patients receiving IVF plus LD versus 42 with IVF only. Meta
      analyses on shunt dependency showed an absolute risk reduction of 24% for the
      intervention (LD, 2.2% [1 of 45] vs no-LD, 26.2% [11 of 42]; odds ratio [OR] =
      0.062; confidence interval [CI], 0.011-0.361; p = 0.002). Secondary endpoints did
      not show significant differences for CSF infections (OR = 0.869;CI, 0.445-1.695;
      p = 0.680) and functional outcome at 90 days (OR = 0.478; CI, 0.190-1.201; p =
      0.116), yet bleeding complications were significantly reduced in favor of the
      intervention (OR = 0.401; CI, 0.302-0.532; p < 0.001). INTERPRETATION: The
      present trial and individual patient data meta-analyses provide evidence that, in
      patients with severe IVH, as compared to IVF alone, a combined approach of IVF
      plus LD treatment is feasible and safe and significantly reduces rates of
      permanent shunt dependency for aresorptive hydrocephalus post-ICH. ANN NEUROL
      2017;81:93-103.

PMID- 27888609
TI  - Effects of lorcaserin on pre-existing valvulopathy: A pooled analysis of phase 3
      trials.
AB  - OBJECTIVE: To evaluate the effects of lorcaserin in patients with pre-existing
      Food and Drug Administration (FDA)-defined valvulopathy. METHODS: This is a
      pooled, post hoc analysis of three Phase 3 studies. BLOOM and BLOSSOM patients
      were 18 to 65 years of age without diabetes and with a body mass index (BMI) of
      27 to 29.9 kg/m2 and >=1 weight-related comorbidity or a BMI of 30 to 45 kg/m2 .
      BLOOM-DM patients had a BMI of 27 to 45 kg/m2 and type 2 diabetes. Patients were
      treated with placebo, lorcaserin 10 mg once daily, or lorcaserin 10 mg twice
      daily. Serial echocardiographs were obtained at baseline and every 6 months.
      RESULTS: Included patients (N = 169) had FDA-defined valvulopathy at baseline and
      a week 52 echocardiogram. At week 52, 35.5% and 52.7% of patients experienced
      changes from baseline in aortic and mitral regurgitation, respectively.
      Numerically greater proportions of patients taking lorcaserin versus placebo had
      decreases in aortic (33.0% vs. 28.3%) or mitral (41.3% vs. 36.7%) regurgitation.
      Fewer patients taking lorcaserin versus placebo had increases in aortic (2.8% vs.
      6.7%) or mitral (8.3% vs. 21.7%) regurgitation. No adverse event-related
      discontinuation was due to a valve problem. CONCLUSIONS: These data suggest that
      lorcaserin does not adversely affect valvular disease in patients with pre
      existing FDA-defined valvulopathy.

PMID- 27888613
TI  - PSMC2 is up-regulated in osteosarcoma and regulates osteosarcoma cell
      proliferation, apoptosis and migration.
AB  - Proteasome 26S subunit ATPase 2 (PSMC2) is a recently identified gene potentially
      associated with certain human carcinogenesis. However, the expressional
      correlation and functional importance of PSMC2 in osteosarcoma is still unclear.
      Current study was focused on elucidating the significance of PSMC2 on malignant
      behaviors in osteosarcoma including proliferation, apoptosis, colony formation,
      migration as well as invasion. The high protein levels of PSMC2 in osteosarcoma
      samples were identified by tissue microarrays analysis. Besides, its expression
      in the levels of mRNA and protein was also detected in four different
      osteosarcoma cell lines by real-time PCR and western blotting separately.
      Silencing PSMC2 by RNA interference in osteosarcoma cell lines (SaoS-2 and MG-63)
      would significantly suppress cell proliferation, enhance apoptosis, accelerate
      G2/M phase and/or S phase arrest, and decrease single cell colony formation.
      Similarly, pharmaceutical inhibition of proteasome with MG132 would mimic the
      PSMC2 depletion induced defects in cell cycle arrest, apoptosis and colonies
      formation. Silencing of PSMC2 was able to inhibit osteosarcoma cell motility,
      invasion as well as tumorigenicity in nude mice. Moreover, the gene microarray
      indicated knockdown of PSMC2 notably changed a number of genes, especially some
      cancer related genes including ITGA6, FN1, CCND1, CCNE2 and TGFbetaR2, and whose
      expression changes were further confirmed by western blotting. Our data suggested
      that PSMC2 may work as an oncogene for osteosarcoma and that inhibition of PSMC2
      may be a therapeutic strategy for osteosarcoma treatment.

PMID- 27888610
TI  - cAMP-independent signal pathways stimulate hyphal morphogenesis in Candida
      albicans.
AB  - The fungal pathogen Candida albicans can transition from budding to hyphal
      growth, which promotes biofilm formation and invasive growth into tissues.
      Stimulation of adenylyl cyclase to form cAMP induces hyphal morphogenesis. The
      failure of cells lacking adenylyl cyclase (cyr1Delta) to form hyphae has
      suggested that cAMP signaling is essential for hyphal growth. However, cyr1Delta
      mutants also grow slowly and have defects in morphogenesis, making it unclear
      whether hyphal inducers must stimulate cAMP, or if normal basal levels of cAMP
      are required to maintain cellular health needed for hyphal growth. Interestingly,
      supplementation of cyr1Delta cells with low levels of cAMP enabled them to form
      hyphae in response to the inducer N-acetylglucosamine (GlcNAc), suggesting that a
      basal level of cAMP is sufficient for stimulation. Furthermore, we isolated
      faster-growing cyr1Delta pseudorevertant strains that can be induced to form
      hyphae even though they lack cAMP. The pseudorevertant strains were not induced
      by CO2 , consistent with reports that CO2 directly stimulates adenylyl cyclase.
      Mutational analysis showed that induction of hyphae in a pseudorevertant strain
      was independent of RAS1, but was dependent on the EFG1 transcription factor that
      acts downstream of protein kinase A. Thus, cAMP-independent signals contribute to
      the induction of hyphal responses.

PMID- 27888614
TI  - Hierarchical investigating the predictive value of p53, COX2, EGFR, nm23 in the
      post-operative patients with colorectal carcinoma.
AB  - The aim of this study was to evaluate the correlations between p53, COX2, EGFR,
      nm23 expression and the progression free survival (PFS) of post-operative
      patients with colorectal carcinoma. Immunohistochemistry was used to detect the
      expression of p53, COX2, EGFR and nm23 in 459 specimens from colorectal carcinoma
      patients. Kaplan-Meier estimates, Cox proportional hazard regression analyses and
      hierarchical analyses were performed on the collected data. Kaplan-Meier
      estimates analysis suggested that EGFR expression was as a negative predictor,
      the median PFS of patients with EGFR high expression was 21.73 months, and the
      median PFS of patients with low EGFR expression was 57.83 months (chi2=20.880,
      P<0.001); nm23 expression was positive predictive factor for the prognosis of
      patients with colorectal carcinoma, the median PFS of patients with high nm23
      expression was 37.77 months, and the median PFS was 21.47 months in the patients
      with low nm23 expression (chi2=7.364, P=0.007). Cox regression analysis revealed
      that comparing with the patients with low expression of EGFR, the patients with
      high EGFR expression were at higher risk of tumor progression (HR=1.667,
      P=0.004); Comparing with the patients with high nm23 expression, the patients
      with nm23 low expression had a higher risk of tumor progression (HR=0.412,
      P<0.001); and the risk of tumor progression was higher in the patients with high
      EGFR expression and low nm23 expression (HR=0.245, P<0.001). Hierarchical
      analysis showed that EGFR expression mainly correlates with the PFS of TNM stage
      I-II colorectal cancer patients, the median PFS was 33.53 months in the TNM stage
      I-II colorectal cancer patients with high EGFR expression patients; The median
      PFS of the TNM stage I-II colorectal cancer patients with low EGFR expression was
      70.43 months (chi2=9.530, P=0.002); The median PFS was 19.2 months in the TNM
      stage III-IV colorectal cancer patients with high expression EGFR, the PFS of the
      TNM stage III-IV colorectal cancer patients with low EGFR expression was 37.87
      months (chi2=7.97, P=0.005). nm23 expression mainly correlates with the PFS of
      TNM stage III-IV colorecatal cancer patients. The median PFS was 47.27 months in
      TNM stage I-II colorectal cancer patients with nm23 high expression, the median
      PFS was 48.85 months in TNM stage I-II colorectal cancer patients with low nm23
      expression (chi2=0.101, P=0.750); The median PFS was 28.8 months in TNM stage III
      IV colorectal cancer patients with nm23 high expression, the median PFS was 14.7
      months in TNM stage III-IV colorectal cancer patients with low nm23 expression
      (chi2=13.213, P<0.001). EGFR is mainly a predictive factor for the prognosis of
      post-operative patients with TNM stage I-II colorectal cancer, and nm23 is
      important for predicting the prognosis of patients with stage III-IV, and EGFR
      and nm23 could be as predictor of combination.

PMID- 27888615
TI  - Unconjugated secondary bile acids activate the unfolded protein response and
      induce golgi fragmentation via a src-kinase-dependant mechanism.
AB  - Bile acids are components of gastro-duodenal refluxate and regarded as causative
      agents in oesophageal disease but the precise mechanisms are unknown. Here we
      demonstrate that a specific subset of physiological bile acids affect the protein
      secretory pathway by inducing ER stress, activating the Unfolded Protein Response
      (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells.
      Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA)
      activated the PERK arm of the UPR, via phosphorylation of eIF2alpha and up
      regulation of ATF3, CHOP and BiP/GRP78. UPR activation by these bile acids is
      mechanistically linked with Golgi fragmentation, as modulating the UPR using a
      PERK inhibitor (GSK2606414) or salubrinal attenuated bile acid-induced effects on
      Golgi structure. Furthermore we demonstrate that DCA, CDCA and LA activate Src
      kinase and that inhibition of this kinase attenuated both bile acid-induced
      BiP/GRP78 expression and Golgi fragmentation. This study highlights a novel
      mechanism whereby environmental factors (bile acids) impact important cellular
      processes regulating cell homeostasis, including the UPR and Golgi structure,
      which may contribute to cancer progression in the oesophagus.

PMID- 27888616
TI  - CCL2/EGF positive feedback loop between cancer cells and macrophages promotes
      cell migration and invasion in head and neck squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) represents the most frequent
      malignancy in the head and neck region, and the survival rate has not been
      improved significantly over the past three decades. It has been reported the
      infiltrated macrophages contribute to the malignant progression of HNSCC.
      However, the crosstalk between macrophages and cancer cells remains poorly
      understood. In the present study, we explored interactions between
      monocytes/macrophages and HNSCC cells by establishing the direct co-culture
      system, and found that the crosstalk promoted the migration and invasion of
      cancer cells by enhancing the invadopodia formation through a CCL2/EGF positive
      feedback loop. Our results demonstrated HNSCC cells educated monocytes into M2
      like macrophages by releasing C-C motif chemokine ligand 2 (CCL2, or MCP-1). And
      the M2-like macrophages secreted epithelial growth factor (EGF), which increased
      the motility of HNSCC cells by enhancing the invadopodia formation. These
      subcellular pseudopodia degraded extracellular matrix (ECM), facilitating tumor
      local invasion and distant metastasis. Moreover, EGF up-regulated CCL2 expression
      in HNSCC cells, which recruited monocytes and turned them into M2-like
      macrophages, thus forming a positive feedback paracrine loop. Finally, we
      reported that curcumin, a powerful natural drug, suppressed the production of EGF
      and CCL2 in macrophages and cancer cells, respectively, blocking the feedback
      loop and suppressing the migration and invasion of HNSCC cells. These results
      shed light on the possibilities and approaches based on targeting the crosstalk
      between cancer cells and monocytes/macrophages in HNSCC for potential cancer
      therapy.

PMID- 27888617
TI  - Suppression of osteopontin inhibits chemically induced hepatic carcinogenesis by
      induction of apoptosis in mice.
AB  - Previous clinical reports have found elevated osteopontin (OPN) levels in tumor
      tissues to be indicative of greater malignancy in human hepatocellular carcinoma
      (HCC). However, the role of OPN on carcinogenesis and its underlying mechanism
      remain unclear. In the present study, we investigated the oncogenic role of OPN
      in diethylnitrosamine (DEN)-induced hepatic carcinogenesis in mice. The overall
      incidence of hepatic tumors at 36 weeks was significantly lower in OPN knockout
      (KO) mice than in wild-type (WT) mice. Apoptosis was significantly enhanced in
      OPN KO mice, and was accompanied by the downregulation of epidermal growth factor
      receptor (EGFR). In the in vitro study, OPN suppression also led to lower mRNA
      and protein levels of EGFR associated with the downregulation of c-Jun in Hep3B
      and Huh7 human HCC cells lines, which resulted in increased apoptotic cell death
      in both cell lines. Moreover, a positive correlation was clearly identified
      between the expression of OPN and EGFR in human HCC tissues. These data
      demonstrate that the OPN deficiency reduced the incidence of chemically induced
      HCC by suppressing EGFR-mediated anti-apoptotic signaling. An important
      implication of our findings is that OPN positively contributes to hepatic
      carcinogenesis.

PMID- 27888620
TI  - Identification of different ALK mutations in a pair of neuroblastoma cell lines
      established at diagnosis and relapse.
AB  - Anaplastic Lymphoma Kinase (ALK) is a transmembrane receptor kinase that belongs
      to the insulin receptor superfamily and has previously been shown to play a role
      in cell proliferation, migration and invasion in neuroblastoma. Activating ALK
      mutations are reported in both hereditary and sporadic neuroblastoma tumours, and
      several ALK inhibitors are currently under clinical evaluation as novel
      treatments for neuroblastoma. Overall, mutations at codons F1174, R1275 and F1245
      together account for ~85% of reported ALK mutations in neuroblastoma. NBLW and
      NBLW-R are paired cell lines originally derived from an infant with metastatic
      MYCN amplified Stage IVS (Evans Criteria) neuroblastoma, at diagnosis and
      relapse, respectively. Using both Sanger and targeted deep sequencing, this study
      describes the identification of distinct ALK mutations in these paired cell
      lines, including the rare R1275L mutation, which has not previously been reported
      in a neuroblastoma cell line. Analysis of the sensitivity of NBLW and NBLW-R
      cells to a panel of ALK inhibitors (TAE-684, Crizotinib, Alectinib and
      Lorlatinib) revealed differences between the paired cell lines, and overall NBLW
      R cells with the F1174L mutation were more resistant to ALK inhibitor induced
      apoptosis compared with NBLW cells. This pair of cell lines represents a valuable
      pre-clinical model of clonal evolution of ALK mutations associated with
      neuroblastoma progression.

PMID- 27888619
TI  - Tetraspanin CD151 as an emerging potential poor prognostic factor across solid
      tumors: a systematic review and meta-analysis.
AB  - Tetraspanin CD151, also known as PETA-3 or SFA-1, has been reported to predict
      prognosis in various solid tumors. Yet, the results of these studies remained
      inconclusive. Here, we performed this meta-analysis of relevant studies published
      on the topic to quantitatively evaluate the clinicopathological significance of
      CD151 in solid tumors. The relevant articles were identified via searching the
      PubMed, Web of Science and Embase database. The pooled hazard ratios (HRs) and
      corresponding 95% confidence intervals (CI) of overall survival (OS) and disease
      free survival (DFS) were calculated to evaluate the prognostic value of CD151
      expression in patients with solid tumors. A total of 19 studies involving 4, 270
      participants were included in the study, we drew the conclusion that CD151
      overexpression was associated with statistically significant poor OS (pooled HR =
      1.498, 95% CI = 1.346-1.667, P<0.001) and poor DFS (pooled HR = 1.488, 95% CI =
      1.314-1.685, P<0.001). Furthermore, the subgroup analysis revealed that the
      associations between CD151 overexpression and the outcome endpoints (OS or TTP)
      were significant within the Asian region and European, as well in patients with
      breast cancer or gastric cancer. Taken together, the incorporative HR showed
      CD151 overexpression was associated with poor survival in human solid tumors.
      CD151 could be a valuable prognosis biomarker or a potential therapeutic target
      of solid tumors.

PMID- 27888621
TI  - Intraperitoneal ziv-aflibercept effectively manages refractory ascites in
      colorectal cancer patients.
AB  - Ascites related to metastatic colorectal cancer (mCRC) reduces patient survival
      and quality of life, and systemic chemotherapy is largely ineffective for
      managing ascites. Here, we examined the clinical efficacy of intraperitoneal (IP)
      ziv-aflibercept for managing refractory ascites in 15 mCRC patients who did not
      respond to standard chemotherapy. Fifty or 100 mg of ziv-aflibercept in 100 mL of
      saline solution were infused through a pigtail catheter and retained for 24 h.
      When the ascites drainage volumes were subsequently monitored, 73.3% of patients
      showed an objective response (OR) to IP ziv-aflibercept treatment. Patients with
      low Eastern Cooperative Oncology Group (ECOG) performance status or with serum
      ascites albumin gradients (SAAG) less than 1.1 g/dL had better responses to
      treatment, and 4 patients with SAAG less than 1.1 g/dL showed rapid objective
      responses (rOR). These findings indicate that intraperitoneal ziv-aflibercept
      therapy may be a highly effective means of treating refractory ascites in mCRC
      patients, and that SAAG may be predictive of a rapid response to this treatment.

PMID- 27888618
TI  - Involvement of inflammation and its related microRNAs in hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed type of
      cancer. The tumor inflammatory microenvironment regulates almost every step
      towards liver tumorigenesis and subsequent progression, and regulation of the
      inflammation-related signaling pathways, cytokines, chemokines and non-coding
      RNAs influences the proliferation, migration and metastasis of liver tumor cells.
      Inflammation fine-tunes the cancer microenvironment to favor epithelial
      mesenchymal transition, in which cancer stem cells maintain tumorigenic
      potential. Emerging evidence points to inflammation-related microRNAs as crucial
      molecules to integrate the complex cellular and molecular crosstalk during HCC
      progression. Thus understanding the mechanisms by which inflammation regulates
      microRNAs might provide novel and admissible strategies for preventing,
      diagnosing and treating HCC. In this review, we will update three hypotheses of
      hepatocarcinogenesis and elaborate the most predominant inflammation signaling
      pathways, i.e. IL-6/STAT3 and NF-kappaB. We also try to summarize the crucial
      tumor-promoting and tumor-suppressing microRNAs and detail how they regulate HCC
      initiation and progression and collaborate with other critical modulators in this
      review.

PMID- 27888622
TI  - Quantification and expert evaluation of evidence for chemopredictive biomarkers
      to personalize cancer treatment.
AB  - Predictive biomarkers have the potential to facilitate cancer precision medicine
      by guiding the optimal choice of therapies for patients. However, clinicians are
      faced with an enormous volume of often-contradictory evidence regarding the
      therapeutic context of chemopredictive biomarkers.We extensively surveyed public
      literature to systematically review the predictive effect of 7 biomarkers claimed
      to predict response to various chemotherapy drugs: ERCC1-platinums, RRM1
      gemcitabine, TYMS-5-fluorouracil/Capecitabine, TUBB3-taxanes, MGMT-temozolomide,
      TOP1-irinotecan/topotecan, and TOP2A-anthracyclines. We focused on studies that
      investigated changes in gene or protein expression as predictors of drug
      sensitivity or resistance. We considered an evidence framework that ranked
      studies from high level I evidence for randomized controlled trials to low level
      IV evidence for pre-clinical studies and patient case studies.We found that
      further in-depth analysis will be required to explore methodological issues,
      inconsistencies between studies, and tumor specific effects present even within
      high evidence level studies. Some of these nuances will lend themselves to
      automation, others will require manual curation. However, the comprehensive
      cataloging and analysis of dispersed public data utilizing an evidence framework
      provides a high level perspective on clinical actionability of these protein
      biomarkers. This framework and perspective will ultimately facilitate clinical
      trial design as well as therapeutic decision-making for individual patients.

PMID- 27888623
TI  - Recombined humanized endostatin (Endostar) combined with chemotherapy for
      advanced bone and soft tissue sarcomas in stage IV.
AB  - PURPOSE: This retrospective case-series study evaluated efficacy and safety of
      Endostar combined with chemotherapy in the treatment of advanced bone and soft
      tissue sarcomas in stage IV. MATERIALS AND METHODS: Forty-seven patients
      diagnosed with stage IV bone and soft tissue sarcomas and treated with
      chemotherapy in Tianjin Medical University Cancer Institute & Hospital were
      reviewed. Of these patients, 23 patients were treated with Endostar plus
      chemotherapy (designated as combined group), and 24 patients received only
      chemotherapy (designated as control group). Progression-free survival (PFS),
      overall survival (OS), objective response rate (ORR) and clinical benefit
      response (CBR) were analyzed to find the difference between these two groups with
      the purpose to investigate the role of Endostar in metastatic sarcomas. RESULTS:
      Endostar combined with chemotherapy had significantly increased PFS. In the
      combined group and control groups, the median PFS (8.6 months versus 4.4 months)
      and the CBR (47.8% versus 16.7%) showed significant difference (P = 0.032), while
      the median overall survival (11.7 months versus 10.6 months, P = 0.658) and the
      ORR (17.4% versus 8.3%, P = 0.167) showed no significant difference. The common
      grade 3-4 side effects for both groups were myelosuppression and transient
      elevation of transaminases. CONCLUSION: Endostar combined with chemotherapy had
      significant activity to increase the PFS and improve CBR in patients with
      advanced sarcomas, with tolerable side effects.

PMID- 27888624
TI  - RhoA regulates resistance to irinotecan by regulating membrane transporter and
      apoptosis signaling in colorectal cancer.
AB  - Colorectal cancer (CRC) is a major cause of mortality and morbidity worldwide.
      While surgery remains the mainstay of treatment in early stage CRC, chemotherapy
      is usually given to prolong the overall survival and improve the quality of life
      for metastatic colorectal cancer (mCRC). But drug resistance is one of the major
      hurdles of mCRC treatment, and the underlying mechanisms are still largely
      unknown. In this study, we show that, compared with parental cells, RhoA is up
      regulated in irinotecan (CPT-11)-resistant CRC cells. Furthermore, inhibition of
      RhoA in drug resistant cells, at least partially, rescues the resistance against
      irinotecan and increases the sensitivity to other chemotherapeutic drug by
      inhibiting expression of MDR1, MRP1and GSTP1, promotes apoptosis by suppressing
      the expression of BCL-XL and Bcl-2 and increasing Bax expression, and
      significantly decreases side population cells. Our results suggest that, in
      addition to survival, proliferation, migration, adhesion, cell cycle and gene
      transcription, RhoA is also involved in chemoresistance by regulating the
      expression of membrane transporter and apoptosis protein in colorectal cancer.
      They raise an interesting possibility that the expression of RhoA may indicate a
      poor prognosis due to the high probability to therapy resistance and, on the
      other hand, inhibition of RhoA activity and function may overcome chemoresistance
      and improve the effectiveness of clinical treatment of CRC.

PMID- 27888625
TI  - TRIM11, a direct target of miR-24-3p, promotes cell proliferation and inhibits
      apoptosis in colon cancer.
AB  - TRIM11 (tripartite motif-containing protein 11) is an E3 ubiquitin ligase
      recently identified as an oncogene in malignant glioma and lung cancer. In the
      present study, we report that expression of TRIM11 was increased in colon cancer
      (CC) tissue relative to paired normal tissues and that higher TRIM11 levels
      predicted poor overall survival (OS) and disease-free survival (DFS) in CC
      patients. Mechanistically, we showed that miR-24-3p downregulation contributes to
      TRIM11 upregulation in CC. We also demonstrated that TRIM11 overexpression
      promotes cell proliferation and colony formation and inhibits apoptosis in CC,
      while knocking down TRIM11 using CRISPR/Cas9-mediated genome editing inhibited
      cell proliferation and induced apoptosis. Silencing TRIM11 in vivo decreased
      tumor growth. These findings indicate that TRIM11 facilitates CC progression by
      promoting cell proliferation and inhibiting apoptosis and that the novel miR-24
      3p/TRIM11 axis may be a useful new target for treating patients with CC.

PMID- 27888627
TI  - Identification of differentially expressed genes in the development of
      osteosarcoma using RNA-seq.
AB  - OBJECTIVE: Osteosarcoma (OS) is a malignant bone tumor with high morbidity in
      young adults and adolescents. This study aimed to discover potential early
      diagnosis biomarkers in OS. RESULTS: In total, 111 differentially expressed genes
      (DEGs) were identified in primary OS compared with normal controls and 235 DEGs
      were identified in metastatic OS compared with primary OS. AURKB and PPP2R2B were
      the significantly up-regulated and down-regulated hub proteins, respectively, in
      the PPI protein-protein network (PPI) network of primary OS. ISG15 and BTRC were
      the significantly up-regulated and down-regulated hub proteins, respectively, in
      the network of metastatic OS. The DEGs in metastatic OS compared with primary OS
      were significantly enriched in the arachidonic acid metabolism, malaria, and
      chemokine signaling pathways. Finally, we employed quantitative real-time
      polymerase chain reaction (qRT-PCR) to validate the expression levels of
      candidate DEGs and the results indicated that our bioinformatics approach was
      acceptable. MATERIALS AND METHODS: The mRNA expression profiling of 20 subjects
      was obtained through high-throughput RNA-sequencing. DEGs were identified between
      primary OS and normal Control, and between primary OS and metastatic OS,
      respectively. Functional annotation and PPI networks were used to obtain insights
      into the functions of DEGs. qRT-PCR was performed to detect the expression levels
      of dysregulated genes in OS. CONCLUSIONS: Our work might provide groundwork for
      the further exploration of tumorigenesis and metastasis mechanisms of OS.

PMID- 27888626
TI  - Interleukin-18 deteriorates Fabry cardiomyopathy and contributes to the
      development of left ventricular hypertrophy in Fabry patients with GLA IVS4+919
      G>A mutation.
AB  - RATIONALE: A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry
      disease of the later-onset cardiac phenotype, has been reported in Taiwan.
      However, suitable biomarkers or potential therapeutic surrogates for Fabry
      cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT)
      remain unknown. OBJECTIVE: Using FC patients carrying IVS4+919 G>A mutation, we
      constructed an induced pluripotent stem cell (iPSC)-based disease model to
      investigate the pathogenetic biomarkers and potential therapeutic targets in ERT
      treated FC. RESULTS AND METHODS: The iPSC-differentiated cardiomyocytes derived
      from FC-patients (FC-iPSC-CMs) carried IVS4+919 G>A mutation recapitulating FC
      characteristics, including low alpha-galactosidase A enzyme activity, cellular
      hypertrophy, and massive globotriaosylceramide accumulation. Microarray analysis
      revealed that interleukin-18 (IL-18), a pleiotropic cytokine involved in various
      myocardial diseases, was the most highly upregulated marker in FC-iPSC-CMs.
      Meanwhile, IL-18 levels were found to be significantly elevated in the culture
      media of FC-iPSC-CMs and patients' sera. Notably, the serum IL-18 levels were
      highly paralleled with the progression of left ventricular hypertrophy in Fabry
      patients receiving ERT. Finally, using FC-iPSC-CMs as in vitro FC model,
      neutralization of IL-18 with specific antibodies combined with ERT
      synergistically reduced the secretion of IL-18 and the progression of
      cardiomyocyte hypertrophy in FC-iPSC-CMs. CONCLUSION: Our data demonstrated that
      cardiac IL-18 and circulating IL-18 are involved in the pathogenesis of FC and
      LVH. IL-18 may be a novel marker for evaluating ERT efficacy, and targeting IL-18
      might be a potential adjunctive therapy combined with ERT for the treatment of
      advanced cardiomyopathy in FC patients with IVS4+919 G>A mutation.

PMID- 27888628
TI  - Impact of epidemiological characteristics of supratentorial gliomas in adults
      brought about by the 2016 world health organization classification of tumors of
      the central nervous system.
AB  - The latest World Health Organization (WHO) classification of tumors of the
      central nervous system (CNS) integrates both histological and molecular features
      in the definition of diagnostic entities. This new approach enrolls novel
      entities of gliomas. In this study, we aimed to reveal the epidemiological
      characteristics, including age at diagnosis, gender ratio, tumor distribution and
      survival, of these new entities. We retrospectively reclassified 1210 glioma
      samples according to the 2016 CNS WHO diagnostic criteria. In our cohort,
      glioblastoma multiforme (GBM) with wildtype isocitrate dehydrogenase (IDH) was
      the most common malignant tumor in the brain. Almost all gliomas were more
      prevalent in males, especially in the cluster of WHO grade III gliomas and IDH
      wildtype GBM. Age at diagnosis was directly proportional to tumor grade. With
      respect to the distribution by histology, we found that gliomas concurrent with
      IDH-mutant and 1p/19q-codeleted or with single IDH-mutant were mainly distributed
      in frontal lobe, while those with IDH-wildtype were dominant in temporal lobe.
      Lesions located in insular lobe were more likely to be IDH-mutant astrocytoma. In
      summary, our results elucidated the epidemiological characteristics as well as
      the regional constituents of these new gliomas entities, which could bring
      insights into tumorigenesis and personalized treatment of Chinese glioma
      population.

PMID- 27888629
TI  - Inhibition of BCR signaling using the Syk inhibitor TAK-659 prevents stroma
      mediated signaling in chronic lymphocytic leukemia cells.
AB  - Proliferation and survival of chronic lymphocytic leukemia (CLL) cells depend on
      microenvironmental signals coming from lymphoid organs. One of the key players
      involved in the crosstalk between CLL cells and the microenvironment is the B
      cell receptor (BCR). Syk protein, a tyrosine kinase essential for BCR signaling,
      is therefore a rational candidate for targeted therapy in CLL. Against this
      background, we tested the efficacy of the highly specific Syk inhibitor TAK-659
      in suppressing the favorable signaling derived from the microenvironment. To ex
      vivo mimic the microenvironment found in the proliferation centers, we co
      cultured primary CLL cells with BM stromal cells (BMSC), CD40L and CpG ODN along
      with BCR stimulation. In this setting, TAK-659 inhibited the microenvironment
      induced activation of Syk and downstream signaling molecules, without inhibiting
      the protein homologue ZAP-70 in T cells. Importantly, the pro-survival,
      proliferative, chemoresistant and activation effects promoted by the
      microenvironment were abrogated by TAK-659, which furthermore blocked CLL cell
      migration toward BMSC, CXCL12, and CXCL13. Combination of TAK-659 with other BCR
      inhibitors showed synergistic effect in inducing apoptosis, and the sequential
      addition of TAK-659 in ibrutinib-treated CLL cells induced significantly higher
      cytotoxicity. These findings provide a strong rationale for the clinical
      development of TAK-659 in CLL.

PMID- 27888631
TI  - Autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic
      reticulum stress and oxidative stress.
AB  - To study the impact of autophagy on alveolar macrophage apoptosis and its
      mechanism in the early stages of hypoxia, we established a cell hypoxia
      reoxygenation model and orthotopic left lung ischemia-reperfusion model. Rat
      alveolar macrophages stably expressing RFP-LC3 were treated with autophagy
      inhibitor (3-methyladenine, 3-MA) or autophagy promoter (rapamycin), followed by
      hypoxia-reoxygenation treatment 2 h, 4 h or 6 h later. Twenty Sprague-Dawley male
      rats were randomly divided into four different groups: no blocking of left lung
      hilum (model group), left lung hilum blocked for 1h with DMSO lavage (control
      group), left lung hilum blocked for 1 h with 100 ml/kg 3-MA (5 MUmol/L) lavage (3
      MA group), and left lung hilum blocked for 1 h with 100 ml/kg rapamycin (250
      nmol/L) lavage (rapamycin group). Rapamycin decreased the unfolded protein
      response, which reduced endoplasmic reticulum stress-mediated apoptosis in the
      presence of oxygen deficiency. Rapamycin increased superoxide dismutase
      activities and decreased malondialdehyde levels, whereas 3-MA decreased
      superoxide dismutase activities and increased malondialdehyde levels. Thus,
      autophagy decreases alveolar macrophage apoptosis by attenuating endoplasmic
      reticulum stress and oxidative stress in the early stage of hypoxia in vitro and
      in vivo. This could represent a new approach to protecting against lung ischemia
      reperfusion injury.

PMID- 27888630
TI  - The association of variants in PNPLA3 and GRP78 and the risk of developing
      hepatocellular carcinoma in an Italian population.
AB  - Hepatocellular carcinoma (HCC) has one of the worst prognoses amongst all
      malignancies. It commonly arises in patients with established liver disease and
      the diagnosis often occurs at an advanced stage. Genetic variations, such as
      single nucleotide polymorphisms (SNPs), may alter disease risk and thus may have
      use as predictive markers of disease outcome. The aims of this study were (i) to
      assess the association of two SNPs, rs430397 in GRP78 and rs738409 in PNPLA3 with
      the risk of developing HCC in a Sicilian association cohort and, (ii) to use a
      machine learning technique to establish a predictive combinatorial phenotypic
      model for HCC including rs430397 and rs738409 genotypes and clinical and
      laboratory attributes. The controls comprised of 304 healthy subjects while the
      cases comprised of 170 HCC patients the majority of whom had hepatitis C (HCV)
      related cirrhosis. Significant associations were identified between the risk of
      developing HCC and both rs430397 (p=0.0095) and rs738409 (p=0.0063). The
      association between rs738409 and HCC was significantly stronger in the HCV
      positive cases. In the best prediction model, represented graphically by a
      decision tree with an acceptable misclassification rate of 17.0%, the A/A and G/A
      genotypes of the rs430397 variant were fixed and combined with the three rs738409
      genotypes; the attributes were age, sex and alcohol. These results demonstrate
      significant associations between both rs430397 and rs738409 and HCC development
      in a Sicilian cohort. The combinatorial predictive model developed to include
      these genetic variants may, if validated in independent cohorts, allow for
      earlier diagnosis of HCC.

PMID- 27888632
TI  - VENTX induces expansion of primitive erythroid cells and contributes to the
      development of acute myeloid leukemia in mice.
AB  - Homeobox genes are key regulators in normal and malignant hematopoiesis. The
      human Vent-like homeobox gene VENTX, a putative homolog of the Xenopus laevis
      Xvent-2 gene, was shown to be highly expressed in normal myeloid cells and in
      patients with acute myeloid leukemia. We now demonstrate that constitutive
      expression of VENTX suppresses expression of genes responsible for terminal
      erythroid differentiation in normal CD34+ stem and progenitor cells.
      Transplantation of bone marrow progenitor cells retrovirally engineered to
      express VENTX caused massive expansion of primitive erythroid cells and partly
      acute erythroleukemia in transplanted mice. The leukemogenic potential of VENTX
      was confirmed in the AML1-ETO transplantation model, as in contrast to AML1-ETO
      alone co-expression of AML1-ETO and VENTX induced acute myeloid leukemia, partly
      expressing erythroid markers, in all transplanted mice. VENTX was highly
      expressed in patients with primary human erythroleukemias and knockdown of VENTX
      in the erythroleukemic HEL cell line significantly blocked cell growth. In
      summary, these data indicate that VENTX is able to perturb erythroid
      differentiation and to contribute to myeloid leukemogenesis when co-expressed
      with appropriate AML oncogenes and point to its potential significance as a novel
      therapeutic target in AML.

PMID- 27888633
TI  - Toll-like receptor 9 expression is associated with breast cancer sensitivity to
      the growth inhibitory effects of bisphosphonates in vitro and in vivo.
AB  - Bisphosphonates are standard treatments for bone metastases. When given in the
      adjuvant setting, they reduce breast cancer mortality and recurrence in bone but
      only among post-menopausal patients. Optimal drug use would require biomarker
      based patient selection. Such biomarkers are not yet in clinical use. Based on
      the similarities in inflammatory responses to bisphosphonates and Toll-like
      receptor (TLR) agonists, we hypothesized that TLR9 expression may affect
      bisphosphonate responses in cells. We compared bisphosphonate effects in breast
      cancer cell lines with low or high TLR9 expression. We discovered that cells with
      decreased TLR9 expression are significantly more sensitive to the growth
      inhibitory effects of bisphosphonates in vitro and in vivo. Furthermore, cancer
      growth-promoting effects seen with some bisphosphonates in some control shRNA
      cells were not detected in TLR9 shRNA cells. These differences were not
      associated with inhibition of Rap1A prenylation or p38 phosphorylation, which are
      known markers for bisphosphonate activity. However, TLR9 shRNA cells exhibited
      increased sensitivity to ApppI, a metabolite that accumulates in cells after
      bisphosphonate treatment. We conclude that decreased TLR9-expression sensitizes
      breast cancer cells to the growth inhibitory effects of bisphosphonates. Our
      results suggest that TLR9 should be studied as a potential biomarker for adjuvant
      bisphosphonate sensitivity among breast cancer patients.

PMID- 27888634
TI  - Targeting protein kinase CK2 suppresses bladder cancer cell survival via the
      glucose metabolic pathway.
AB  - Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that
      promotes cell proliferation and resists apoptosis. Elevated CK2 expression has
      been demonstrated in several solid tumors. The expression of CK2alpha in bladder
      cancer was elevated in tumor tissues compared with that in adjacent normal
      tissues. Amplified expression of CK2alpha was highly correlated with histological
      grade in bladder cancer(P = 0.024). Knockdown of CK2alpha in bladder cancer cell
      lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower
      phosphorylated AKT. Moreover, low CK2alpha levels suppressed cell growth, and
      similar results could be reproduced after treatment with CX-4945 with a dose
      dependent response. CX-4945 inhibited migration and induced apoptosis.
      Furthermore, knockdown of CK2alpha decreased the tumorigenicity of bladder cancer
      cells in vivo. This study is the first to report that CK2 increases glucose
      metabolism in human bladder cancer. Blocking CK2 function may provide novel
      diagnostic and potential therapeutic.

PMID- 27888637
TI  - Standing on the shoulders of giants.

PMID- 27888636
TI  - Factors that influence treatment delay in patients with colorectal cancer.
AB  - A prospective study was performed of patients diagnosed with colorectal cancer
      (CRC), distinguishing between colonic and rectal location, to determine the
      factors that may provoke a delay in the first treatment (DFT) provided.2749
      patients diagnosed with CRC were studied. The study population was recruited
      between June 2010 and December 2012. DFT is defined as time elapsed between
      diagnosis and first treatment exceeding 30 days.Excessive treatment delay was
      recorded in 65.5% of the cases, and was more prevalent among rectal cancer
      patients. Independent predictor variables of DFT in colon cancer patients were a
      low level of education, small tumour, ex-smoker, asymptomatic at diagnosis and
      following the application of screening. Among rectal cancer patients, the
      corresponding factors were primary school education and being asymptomatic.We
      conclude that treatment delay in CRC patients is affected not only by
      clinicopathological factors, but also by sociocultural ones. Greater attention
      should be paid by the healthcare provider to social groups with less formal
      education, in order to optimise treatment attention.

PMID- 27888638
TI  - Should surgeons routinely inform patients about risks of taste dysfunction after
      tongue base surgery for sleep apnea?

PMID- 27888635
TI  - LncRNAs: the bridge linking RNA and colorectal cancer.
AB  - Long noncoding RNAs (lncRNAs) are transcribed by genomic regions (exceeding 200
      nucleotides in length) that do not encode proteins. While the exquisite
      regulation of lncRNA transcription can provide signals of malignant
      transformation, lncRNAs control pleiotropic cancer phenotypes through
      interactions with other cellular molecules including DNA, protein, and RNA.
      Recent studies have demonstrated that dysregulation of lncRNAs is influential in
      proliferation, angiogenesis, metastasis, invasion, apoptosis, stemness, and
      genome instability in colorectal cancer (CRC), with consequent clinical
      implications. In this review, we explicate the roles of different lncRNAs in CRC,
      and the potential implications for their clinical application.

PMID- 27888639
TI  - Association between body mass index and salivary uric acid among Mexican-origin
      infants, youth and adults: Gender and developmental differences.
AB  - Uric acid (UA) is the end product of the metabolic breakdown of purine
      nucleotides. Recent studies have measured UA in saliva in relation to obesity and
      chronic disease risk. Given the increasing prevalence of metabolic syndrome among
      Latino youth, we examined gender and age differences in salivary uric acid (sUA)
      and weight in a sample of Mexican-origin children (n = 65, 2 months to 18 years,
      49% female) and adults (n = 46, 19-58 years, 72% female). We measured weight,
      height, waist, and hip circumference and collected saliva samples (later assayed
      for sUA). Structural equation models estimated the relationship between age,
      developmental stage, and weight outcomes in relation to sUA levels between
      genders, while controlling for race. Results demonstrate that increased sUA
      levels were related to higher BMI percentiles in females of all ages (beta =
      0.43, p < .001). There were significant differences in sUA levels between
      developmental stages for girls, with female toddlers having the highest sUA
      levels (beta = .28, p = .02). In an interaction between BMI z-score and gender
      between youth and adults, BMI has a larger effect on increasing sUA levels among
      younger girls (beta = 0.27, p < .03) and adult women (beta = 0.33, p = .02).
      Levels of sUA may be gender-specific in relation to BMI and developmental stage.

PMID- 27888640
TI  - Chronotherapy versus conventional statins therapy for the treatment of
      hyperlipidaemia.
AB  - BACKGROUND: Elevated levels of total cholesterol and low-density lipoprotein play
      an important role in the development of atheromas and, therefore, in
      cardiovascular diseases. Cholesterol biosynthesis follows a circadian rhythm and
      is principally produced at night (between 12:00 am and 6:00 am). The adjustment
      of hypolipaemic therapy to biologic rhythms is known as chronotherapy.
      Chronotherapy is based on the idea that medication can have different effects
      depending on the hour at which it is taken. Statins are one of the most widely
      used drugs for the prevention of cardiovascular events. In usual clinical
      practice, statins are administered once per day without specifying the time when
      they should be taken. It is unknown whether the timing of statin administration
      is important for clinical outcomes. OBJECTIVES: To critically evaluate and
      analyse the evidence available from randomised controlled trials regarding the
      effects of chronotherapy on the effectiveness and safety of treating
      hyperlipidaemia with statins. SEARCH METHODS: We searched the CENTRAL, MEDLINE,
      Embase, LILACS, ProQuest Health & Medical Complete, OpenSIGLE, Web of Science
      Conference Proceedings, and various other resources including clinical trials
      registers up to November 2015. We also searched the reference lists of relevant
      reviews for eligible studies. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs), enrolling people with primary or secondary
      hyperlipidaemia. To be included, trials must have compared any chronotherapeutic
      lipid-lowering regimen with statins and any other statin lipid-lowering regimen
      not based on chronotherapy. We considered any type and dosage of statin as
      eligible, as long as the control and experimental arms differed only in the
      timing of the administration of the same statin. Quasi-randomised studies were
      excluded. DATA COLLECTION AND ANALYSIS: We used the standard methodological
      procedures expected by Cochrane. We extracted the key data from studies in
      relation to participants, interventions, and outcomes for safety and efficacy. We
      calculated odds ratios (OR) for dichotomous data and mean differences (MD) for
      continuous data with 95% confidence intervals (CI). Using the GRADE approach, we
      assessed the quality of the evidence and we used the GRADEpro Guideline
      Development Tool to import data from Review Manager to create 'Summary of
      findings' tables. MAIN RESULTS: This review includes eight RCTs (767 participants
      analysed in morning and evening arms). The trials used different lipid-lowering
      regimens with statins (lovastatin: two trials; simvastatin: three trials;
      fluvastatin: two trials; pravastatin: one trial). All trials compared the effects
      between morning and evening statin administration. Trial length ranged from four
      to 14 weeks. We found a high risk of bias in the domain of selective reporting in
      three trials and in the domain of incomplete outcome data in one trial of the
      eight trials included. None of the studies included were judged to be at low risk
      of bias.None of the included RCTs reported data on cardiovascular mortality,
      cardiovascular morbidity, incidence of cardiovascular events, or deaths from any
      cause. Pooled results showed no evidence of a difference in total cholesterol (MD
      4.33, 95% CI -1.36 to 10.01), 514 participants, five trials, mean follow-up 9
      weeks, low-quality evidence), low-density lipoprotein cholesterol (LDL-C) levels
      (MD 4.85 mg/dL, 95% CI -0.87 to 10.57, 473 participants, five trials, mean follow
      up 9 weeks, low-quality evidence), high-density lipoprotein cholesterol (HDL-C)
      (MD 0.54, 95% CI -1.08 to 2.17, 514 participants, five trials, mean follow-up 9
      weeks, low-quality evidence) or triglycerides (MD -8.91, 95% CI -22 to 4.17, 510
      participants, five trials, mean follow-up 9 weeks, low-quality evidence) between
      morning and evening statin administration.With regard to safety outcomes, five
      trials (556 participants) reported adverse events. Pooled analysis found no
      differences in statins adverse events between morning and evening intake (OR
      0.71, 95% CI 0.44 to 1.15, 556 participants, five trials, mean follow-up 9 weeks,
      low-quality evidence). AUTHORS' CONCLUSIONS: Limited and low-quality evidence
      suggested that there were no differences between chronomodulated treatment with
      statins in people with hyperlipidaemia as compared to conventional treatment with
      statins, in terms of clinically relevant outcomes. Studies were short term and
      therefore did not report on our primary outcomes, cardiovascular clinical events
      or death. The review did not find differences in adverse events associated with
      statins between both regimens. Taking statins in the evening does not have an
      effect on the improvement of lipid levels with respect to morning administration.
      Further high-quality trials with longer-term follow-up are needed to confirm the
      results of this review.

PMID- 27888641
TI  - Carotid artery and lower cranial nerve exposure with increasing surgical
      complexity to the parapharyngeal space.
AB  - OBJECTIVES/HYPOTHESIS: To investigate the extent of carotid artery exposure
      attained, including the identification of the external carotid branches and lower
      cranial nerves in five sequential external approaches to the parapharyngeal
      space, and to provide an anatomical algorithm. STUDY DESIGN: Anatomical study.
      METHODS: Six latex-injected adult cadaver heads were dissected in five
      consecutive approaches: transcervical approach with submandibular gland removal,
      posterior extension of the transcervical approach, transcervical approach with
      parotidectomy, parotidectomy with lateral mandibulotomy, and parotidectomy with
      mandibulectomy. The degree of carotid artery exposure attained, external carotid
      branches, and lower cranial nerves visualized was documented. RESULTS: The
      transcervical approach exposed 1.5 cm (Standard Deviation (SD) 0.5) of internal
      carotid artery (ICA) and 1.25 cm (SD 0.25) of external carotid artery (ECA). The
      superior thyroid and facial arteries and cranial nerve XII and XI were
      identified. The posterior extension exposed 2.9 cm (SD 0.7) of ICA and 2.7 cm (SD
      1.0) of ECA. Occipital and ascending pharyngeal arteries were visualized. The
      transparotid approach exposed 4.0 cm (SD 1.1) of ICA and 3.98 cm (SD 1.8) of ECA.
      Lateral mandibulotomy exposed the internal maxillary artery, cranial nerve X, the
      sympathetic trunk, and 4.6 cm (SD 2.4) of ICA. Mandibulectomy allowed for
      complete ECA exposure, cranial nerve IX, lingual nerve, and 6.9 cm (SD 1.3) of
      ICA. CONCLUSION: Approaches for the parapharyngeal space must be based on
      anatomic and biological patient factors. This study provides a guide for the
      skull base surgeon for an extended approach based on the desired anatomic
      exposure. LEVEL OF EVIDENCE: N/A. Laryngoscope, 127:585-591, 2017.

PMID- 27888642
TI  - Histamine H4 receptor gene polymorphisms: a potential predictor of oral H1
      antihistamine efficacy for allergic rhinitis.
AB  - BACKGROUND: Our study aimed to investigate the associations between Histamine H4
      receptor (HRH4) gene polymorphisms (rs77485247, rs74604924, and rs77041280) and
      oral H1 antihistamine efficacy for the treatment of allergic rhinitis (AR)
      patients. METHODS: A total of 142 AR patients were selected as a case group and
      160 healthy individuals were recruited as a control group. Single nucleotide
      polymorphisms (SNPs) in the HRH4 gene were detected using direct sequencing.
      Serum immunoglobulin E (IgE), specific IgE, and eosinophil cationic protein (ECP)
      levels were measured by enzyme-linked immunosorbent assay (ELISA). Clinical
      efficacy was evaluated by the visual analogue scale (VAS). The occurrence of
      adverse reaction was recorded. RESULTS: There were significant differences in the
      distribution frequencies of mutant genotype (TA + AA) and A allele of rs77485247,
      mutant genotype (AT + TT) and T allele of rs74604924, and mutant genotype (AT +
      TT) and T allele of rs77041280 between the case and control groups. AR patients
      with mutant genotype (TA + AA) of rs77485247 and AR patients with mutant genotype
      (AT + TT) of rs77041280 had higher specific IgE, ECP levels, and VAS scores after
      treatment and lower incidence of adverse reactions and total effective rate than
      those with TT genotype and those with AA genotype, respectively. However, for
      rs74604924, there were no differences was found between AR patients with mutant
      genotype (AT + TT) and those with AA genotype. CONCLUSION: Our findings provide
      evidence that HRH4 rs77485247 and rs77041280 polymorphisms may be associated with
      the risk of AR and the efficacy of H1 antihistamines for the treatment of AR
      patients.

PMID- 27888643
TI  - Correlation between the number of allergen sensitizations and immunoglobulin E:
      monosensitization vs polysensitization.
AB  - BACKGROUND: The purpose of this study was to determine if total serum
      immunoglobulin E (IgE) could predict monosensitization compared to
      polysensitization in patients with allergic rhinitis (AR). METHODS: This was a
      retrospective study of a cohort of 1073 patients who underwent allergy testing.
      Differences in total IgE level between unsensitized, monosensitized, and
      polysensitized subjects were calculated. Pearson correlation coefficient was
      calculated to determine whether there was a relationship between total IgE level
      and the number of positive allergen sensitizations. In addition, allergen
      sensitization class was calculated for each allergen sensitization and totaled
      for each patient. Pearson correlation coefficient was calculated to determine the
      relationship between total IgE level and weighted allergen sensitization by
      class. RESULTS: There were 159 patients who were monosensitized compared to 492
      patients who were polysensitized. Of the monosensitized patients, almost 50% (74)
      were sensitized to one or both dust mites. Total IgE was higher in polysensitized
      patients compared to monosensitized compared to controls (p < 0.001). Pearson
      correlation coefficient between total IgE and number of positive allergen
      sensitizations was 0.465 (p <= 0.001). Pearson correlation coefficient between
      total IgE and allergen class-weighted sensitizations was 0.529 (p <= 0.001).
      CONCLUSION: IgE level can be used to predict monosensitization vs
      polysensitization. There is a moderate correlation between total IgE
      sensitization and the number of positive allergen sensitizations, as well as
      allergen class-weighted sensitizations.

PMID- 27888644
TI  - Myrtol standardized affects mucociliary clearance.
AB  - BACKGROUND: Myrtol standardized (Gelomyrtol forte) has been shown to be effective
      in controlling nasal symptoms of rhinosinusitis by promoting mucociliary
      clearance. Our aim was to evaluate the short- and long-term effects of myrtol on
      ciliated columnar cells and goblet cells in an in-vitro setting. METHODS: Nasal
      epithelial cells were harvested (42 days) from an air-liquid interface (ALI)
      culture of human nasal epithelial stem/progenitor cells (hNESPCs), which was
      derived from biopsies of nasal inferior turbinate mucosa. Myrtol 0.1% was applied
      to the ALI culture system at 2 different time-points (day 0 and day 35) on
      progenitor and differentiated cells. Ciliary beat frequency (CBF), supernatant
      fluid, and ciliated and goblet cell markers were evaluated after short- (7 days)
      and long-term (42 days) treatment. RESULTS: In the long-term treatment with
      myrtol, there was an increase in cilia area (type IV beta-tubulin+ , 1.53-fold, p
      = 0.031) and ciliogenesis-related markers (Foxj1 and CP110) with no change in
      CBF, as compared with control. In addition, the short-term myrtol treatment group
      exhibited greater mucin secretion compared with control. CONCLUSION: This study
      demonstrates, through cellular and molecular mechanisms, that myrtol standardized
      enhances the mucus production from goblet cells in the short term, and promotes
      ciliated cell differentiation in the long term.

PMID- 27888645
TI  - Olfaction in patients with allergic rhinitis: an indicator of successful MP
      AzeFlu therapy.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of MP-AzeFlu
      on olfaction and the interaction between severity of allergic rhinitis and
      olfactory improvement after therapy. METHODS: A prospective, multicenter,
      observational study was performed on 47 patients with persistent allergic
      rhinitis. Duration and severity of allergic rhinitis was diagnosed and classified
      using the modified Allergic Rhinitis and its Impact on Asthma (ARIA) criteria and
      the proof of allergen sensitization from positive skin-prick tests, specific
      immonoglobulin E (IgE) in serum, and nasal provocation response. Patients were
      treated with MP-AzeFlu (1 spray/nostril twice daily) over 3 months. Olfactory
      function was assessed at baseline and at 1 and 3 months of therapy using the
      "Sniffin' Sticks" test. In addition, a nasal symptom score was recorded on a
      visual analog scale (VAS) at each given time-point. RESULTS: MP-AzeFlu was found
      to be associated with a significant improvement in TDI score, from 23.7 at
      baseline to 34.2 at 1 month (p < 0.001) and 37.1 at 3 months (p < 0.001) of
      treatment. Furthermore, a highly significant improvement of symptoms over time (p
      < 0.001; VAS at baseline: 84.3; 1 month: 32.4; 3 months: 26.2) could be
      demonstrated. Most importantly, there was a highly significant interaction
      between the severity of allergic rhinitis and olfactory function (p < 0.001) and
      VAS (p < 0.001). CONCLUSION: MP-AzeFlu is associated with olfactory improvement
      in persistent allergic rhinitis patients. Further, the modified ARIA severity
      classification is an indicator of patients' olfactory function. Moreover,
      assessment of olfaction seems to be a reliable indicator of the clinical success
      of antiallergic/antiinflammatory therapy.

PMID- 27888647
TI  - Microarray analysis of the genes associated with osteitis in chronic
      rhinosinusitis.
AB  - OBJECTIVES/HYPOTHESIS: Although numerous studies have examined epithelial
      remodeling in chronic rhinosinusitis (CRS), bone remodeling (osteitis) has only
      recently gained attention as a potential significant contributor to the
      pathophysiology of recalcitrant CRS. The purpose of this study was to compare
      gene expression profiles between osteitic bone and the adjacent diseased mucosa
      in patients with CRS to determine which genes affect mucosal and bony remodeling.
      STUDY DESIGN: Prospective experimental analysis. METHODS: Samples were obtained
      from sites of osteitic bone and overlying mucosa in CRS patients demonstrating
      osteitis on computed tomography and compared to healthy controls. The entire
      transcripted gene expression profile was determined by microarray following RNA
      isolation and compared between tissue samples. The expression differences were
      verified by reverse transcriptase-polymerase chain reaction and
      immunohistochemical staining. RESULTS: Growth differentiation factor 5 and
      exostosin glycosyltransferase 1 were significantly upregulated and positively
      correlated with mucosal eosinophilic inflammation in osteitic bone. Fibroblast
      growth factor was significantly increased in osteitic bone. Additionally, colony
      stimulating factor was positively correlated with the degree of osteitis.
      CONCLUSIONS: These findings will add a new perspective to our current
      understanding of the recalcitrant CRS. LEVEL OF EVIDENCE: NA Laryngoscope,
      127:E85-E90, 2017.

PMID- 27888646
TI  - Corner fracture type spondylometaphyseal dysplasia: Overlap with type II
      collagenopathies.
AB  - Spondylometaphyseal dysplasia (SMD) corner fracture type (also known as SMD
      "Sutcliffe" type, MIM 184255) is a rare skeletal dysplasia that presents with
      mild to moderate short stature, developmental coxa vara, mild platyspondyly,
      corner fracture-like lesions, and metaphyseal abnormalities with sparing of the
      epiphyses. The molecular basis for this disorder has yet to be clarified. We
      describe two patients with SMD corner fracture type and heterozygous pathogenic
      variants in COL2A1. These two cases together with a third case of SMD corner
      fracture type with a heterozygous COL2A1 pathogenic variant previously described
      suggest that this disorder overlaps with type II collagenopathies. The finding of
      one of the pathogenic variants in a previously reported case of
      spondyloepimetaphyseal dysplasia (SEMD) Strudwick type and the significant
      clinical similarity suggest an overlap between SMD corner fracture and SEMD
      Strudwick types. (c) 2016 Wiley Periodicals, Inc.

PMID- 27888648
TI  - Identification and characterization of the distinct expression profiles of
      candidate chemosensory membrane proteins in the antennal transcriptome of
      Adelphocoris lineolatus (Goeze).
AB  - Chemosensory membrane proteins, including odorant receptors (ORs), ionotropic
      receptors (IRs), gustatory receptors (GRs) and sensory neurone membrane proteins
      (SNMPs), are supposed to be crucial macromolecules in the insect olfactory signal
      transduction pathway. The alfalfa plant bug Adelphocoris lineolatus (Goeze)
      (Hemiptera: Miridae) is highly attracted to high-nitrogen or flowering plants and
      destroys many important agricultural crops. We assembled the antennal
      transcriptome of A. lineolatus using Illumina sequencing technology and
      identified a total of 108 transcripts encoding chemosensory membrane proteins (88
      ORs, 12 IRs, four GRs and four SNMPs), amongst which 90 candidates appeared to be
      full length. Subsequently, both semiquantitative reverse transcription PCR and
      quantitative real-time PCR experiments were performed to investigate their tissue
      and sex-biased expression profiles. The results showed that nearly all of the
      108 candidate chemosensory membrane protein genes were largely expressed in adult
      antennae, and some genes additionally displayed significant differences in the
      expression levels between sexes. The results of our phylogenetic analysis and the
      detailed tissue- and sex-biased expression characteristics given here provide an
      important foundation for further understanding of the complex chemoreception
      system of the alfalfa plant bug and other Hemiptera species, which also could
      help us use chemosensory membrane proteins as targets to manipulate insect
      olfactory behaviour and broaden the applications of available tools for insect
      pest control.

PMID- 27888651
TI  - A Digital Standard of Care.

PMID- 27888650
TI  - Closure of the cervical os in patients after fertility preserving treatment for
      early cervical cancer - results of a prospective observational study.
AB  - INTRODUCTION: Up to 50% of the infants delivered after radical vaginal
      trachelectomy (RVT) are born prematurely. An effective strategy to reduce this
      number could be the closure of the cervical os (CCO). PATIENTS AND METHODS:
      Fifteen pregnant patients who had a RVT due to early cervical cancer were
      included in this prospective case control study. All patients were scheduled for
      CCO early in the second trimester. CCO was performed in 12 patients. Their data
      were compared to data from 125 pregnancies after a RVT without CCO. RESULTS: The
      patients who had CCO were compared to patients without CCO. One patient had an
      early rupture of the amniotic membranes prior to CCO. Two patients chose not to
      undergo CCO. In 12 patients CCO was performed without complications. There was no
      early preterm delivery in the CCO group as compared to a rate of 5% in 125
      pregnancies in the non-CCO group. DISCUSSION: We developed a protocol to reduce
      the risk of preterm deliveries after a RVT. Digital examinations should be
      avoided. Vaginal checks for pH can discover ascending infections - the main cause
      of preterm deliveries after a RVT. Infections should be treated adequately. CCO
      can further reduce the risk of preterm deliveries after a RVT.

PMID- 27888652
TI  - Accelerated Orthodontics Using Pulsatile Forces in Orthognathic Surgical
      Patients.

PMID- 27888649
TI  - Prospective, multicenter evaluation of balloon sinus dilation for treatment of
      pediatric chronic rhinosinusitis.
AB  - BACKGROUND: Although balloon sinus dilation is a treatment option for adults with
      chronic rhinosinusitis (CRS), there have been few studies performed in pediatric
      patients. METHODS: This study was designed as a prospective, multicenter, single
      arm investigation. Children (2 to 21 years old) with CRS who had failed medical
      management were treated with balloon sinus dilation and followed to 6 months
      postprocedure. RESULTS: Fifty children were treated at 4 centers; 33 participants
      were 2 to 12 years old (mean +/- standard deviation age: 6.6 +/- 2.2 years) and
      17 participants were >12 to 21 years (mean age: 15.7 +/- 2.5 years). A total of
      157 sinus dilations were attempted (98 maxillary, 30 frontal, and 29 sphenoid
      sinuses) and all were successful with no complications. Significant improvement
      in the Sinus and Nasal Quality of Life Survey (SN-5) was seen for all children
      between baseline and 6 months (4.6 +/- 1.2 vs 1.7 +/- 0.8; p < 0.0001) and 92%
      improved by a minimal clinically important difference (MCID) of 1.0 or more.
      Those children aged 2 to 12 years with standalone balloon dilation also showed
      significant SN-5 improvements between baseline and follow-up (4.5 +/- 1.0 vs 1.9
      +/- 0.8; p < 0.0001). Multivariate regression analysis showed no differences or
      associations of SN-5 improvement at 6 months with the presence of allergy,
      asthma, or concomitant procedures. For adolescents, overall 22-item Sino-Nasal
      Outcome Test (SNOT-22) mean scores were also significantly improved at 6 months
      (42.2 +/- 19.2 vs 10.4 +/- 9.7; p < 0.0001). CONCLUSION: Balloon sinus dilation
      is safe and appears effective for children with CRS aged 2 years and older.

PMID- 27888653
TI  - Simultaneous Intrusion and Distalization Using Miniscrews in the Maxillary
      Tuberosity.

PMID- 27888654
TI  - Assessing the Accuracy of Indirect Bonding with 3D Scanning Technology.

PMID- 27888655
TI  - Correction of Buccolingual Inclination with an Individual Torquing Auxiliary.

PMID- 27888656
TI  - Nonextraction Treatment of an Open Bite with a Preadjusted Lingual Appliance and
      Intermaxillary Elastics.

PMID- 27888658
TI  - A case of composite classical and nodular lymphocyte predominant Hodgkin lymphoma
      with progression to diffuse large B-cell non-Hodgkin lymphoma: Diagnostic
      difficulty in fine-needle aspiration cytology.
AB  - A small percentage of nodular lymphocytic predominant Hodgkin lymphoma (NLPHL)
      progresses to diffuse large B-cell lymphoma (DLBCL). There have also been rare
      reports of gray zone lymphoma with features intermediate between classical
      Hodgkin lymphoma (CHL) and DLBCL. We report a very rare case of composite
      lymphoma (CHL and NLPHL) progressing to DLBCL, and highlight the diagnostic
      difficulty faced during its fine-needle aspiration (FNA) cytology diagnosis. A 65
      year-old woman presented with a right axillary swelling which was subjected to
      FNA cytology. The routine FNA cytology diagnosis was anaplastic large cell
      lymphoma (ALCL) but immunocytochemistry did not support this diagnosis
      completely. The histopathological diagnosis of the excised lymph node was NLPHL
      with progression to DLBCL in our hospital but in a hospital abroad where the
      patient was treated, the reviewed diagnosis was CHL. The patient had a rapid
      downhill course with development of terminal pleural effusion and died
      approximately one year from initial diagnosis.The review of the cyto-histologic
      material along with additional immunocyto/histochemical studies and the clinical
      course of the disease support the diagnosis of a composite lymphoma (CHL and
      NLPHL) with progression to DLBCL. It is suggested that all the three lesions were
      clonally related. Diagn. Cytopathol. 2017;45:262-266. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27888659
TI  - Intraoperative diagnosis of hydatid cyst of the ovary masquerading as tumor.
AB  - Hydatid disease, caused by the larval stage of Echinococcus granulosus, is found
      most commonly in the liver and lungs, but no organ is immune. The ovarian
      involvement is often secondary to a cyst's dissemination localized in a different
      site. Occasionally, the cyst enlarges, thus mimicking an ovarian tumor. Patients
      with hydatid cysts at unusual locations present with atypical presentations and
      pose a diagnostic dilemma. A high index of suspicion is required in order to make
      a correct diagnosis pre-operatively to prevent spillage of the cyst contents
      during surgery. We report a case of hydatid cyst in the ovary in a young female.
      Diagn. Cytopathol. 2017;45:267-269. (c) 2016 Wiley Periodicals, Inc.

PMID- 27888657
TI  - Electroconvulsive Therapy-Induced Brain Structural and Functional Changes in
      Major Depressive Disorders: A Longitudinal Study.
AB  - BACKGROUND This study aimed to study the brain structural and functional changes
      after 8 courses of electroconvulsive therapy (ECT) on patients with major
      depressive disorder (MDD). MATERIAL AND METHODS MRI scans were performed on 12
      depressive patients before and after 8 courses of ECT and compared with those of
      15 normal controls. Data were analyzed by voxel-based morphometry (VBM) using
      SPM8 software. Functional MRI (fMRI) and regional homogeneity (ReHo) analyses
      were used to assess the functional changes after ECT. RESULTS Grey matter volumes
      were smaller in the right cingulate gyrus of depressive patients before ECT
      compared with normal controls. After false discovery rate (FDR) correction, post
      ECT grey matter volumes were increased in bilateral amygdala and hippocampus
      compared with pre-ECT. Resting-state ReHo maps showed significant differences in
      brain activity pre- and post-ECT. Compared with healthy controls, MDD patients
      treated with 8 courses of ECT showed higher ReHo values in the bilateral frontal
      lobe, bilateral parietal lobe, and right caudate nucleus. Decreased ReHo values
      were observed in the right medial temporal gyrus, right superior temporal gyrus,
      right cingulate gyrus, and left anterior cerebellar lobe. CONCLUSIONS Results
      suggested that there were both structural and functional differences between the
      brains of MDD patients and healthy controls. After ECT, both structural and
      functional changes occurred, but without complete recovery to normal. ECT may
      display effects through regulating other brain regions to compensate for the
      original defects.

PMID- 27888660
TI  - Strongyloides in cerebrospinal fluid.

PMID- 27888661
TI  - Use of vimentin immunocytochemical staining for evaluation of atypical cells in
      voided urine samples.
AB  - BACKGROUND: Cytomorphology of exfoliated atypical reactive/repair renal tubular
      cells (RRTC) can resemble atypical urothelial cells thus suggesting a
      differential diagnostic question of urothelial neoplasia in urinary cytology.
      Vimentin expression has been shown in RRTC and used for differentiation from
      atypical urothelial cells. METHODS: The institutional computer database was
      searched for urinary cytology cases with vimentin immunocytochemical staining
      (2008-2012). Original cytopathological diagnoses based on cytomorphology and the
      results of vimentin immunostaining were compared to follow-up data, including
      histopathological diagnosis, subsequent urinary cytopathology reports, and
      clinical findings. RESULTS: Of the 42 cases with vimentin immunocytochemical
      staining, 33 were positive and 9 negative. Consequently, significant renal
      disease was found in 9/33 (27%) of vimentin positive cases and nehrolithiasis in
      4/33 (12%) of vimentin positive and 1/9 (11%) of vimentin negative cases.
      Erythrocyturia of undetermined origin was diagnosed in nine cases (seven vimentin
      positive and two negative). Urinary cytology follow-up was negative in three
      vimentin positive cases. Urothelial carcinoma was found in 3/9 (30%) of vimentin
      negative cases. Thirteen patients were lost to follow-up. CONCLUSIONS: Vimentin
      immunocytochemical staining could be used as an ancillary method for evaluation
      of atypical cells in urinary specimens in selected cases with RRTC exhibiting
      cytological atypia. Unnecessary diagnostic procedures for evaluation of
      urothelial carcinoma could be avoided in vimentin positive cases and further
      diagnostic work-up for evaluation of a significant renal disease could be
      suggested in vimentin positive cases. Diagn. Cytopathol. 2017;45:85-90. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27888663
TI  - Effect of structural carbohydrates and lignin content on the anaerobic digestion
      of paper and paper board materials by anaerobic granular sludge.
AB  - Anaerobic digestion (AD) of lignocellulosic materials is commonly limited by the
      hydrolysis step. Unlike unprocessed lignocellulosic materials, paper and paper
      board (PPB) are processed for their fabrication. Such modifications may affect
      their methane yields and methane production rates. Previous studies have
      investigated the correlation between lignin and biomethane yields of unprocessed
      lignocellulosic materials; nevertheless, there is limited knowledge regarding the
      relationship between the AD kinetic parameters and composition of PPB. This study
      evaluated correlations of methane yields and Monod and Gompertz kinetic
      parameters with structural carbohydrates, lignin, and ash concentration of five
      types of PPBs. All components were used as single and combined independent
      variables in linear regressions to predict methane yield, maximum specific
      methanogenic activity (SMAmax ), saturation constant (Ks ), and lag phase
      (lambda). Additionally, microbial community profiles were obtained for each PPB
      assay. Results showed methane yields ranging from 69.2 +/- 8.61 to 97.2 +/- 2.29%
      of PPB substrates provided. The highest correlation coefficients were obtained
      for SMAmax as function of hemicellulose/(lignin + ash) (R2  = 0.86) and for
      lambda as a function of lignin + cellulose (R2  = 0.85). All other parameters
      exhibited weaker correlations (R2  <= 0.77). Relative abundance analyses revealed
      no major changes in the community profile for each of the substrates evaluated.
      The overall findings of this study are: (i) combinations of structural
      carbohydrates, lignin, and ash used as ratios of degradable to either non
      degradable or slowly degradable fractions predict AD kinetic parameters of PPB
      materials better than single independent variables; and (ii) other components
      added during their fabrication may also influence both methane yield and kinetic
      parameters. Biotechnol. Bioeng. 2017;114: 951-960. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27888662
TI  - Toward high solids loading process for lignocellulosic biofuel production at a
      low cost.
AB  - High solids loadings (>18 wt%) in enzymatic hydrolysis and fermentation are
      desired for lignocellulosic biofuel production at a high titer and low cost.
      However, sugar conversion and ethanol yield decrease with increasing solids
      loading. The factor(s) limiting sugar conversion at high solids loading is not
      clearly understood. In the present study, we investigated the effect of solids
      loading on simultaneous saccharification and co-fermentation (SSCF) of AFEXTM
      (ammonia fiber expansion) pretreated corn stover for ethanol production using a
      xylose fermenting strain Saccharomyces cerevisiae 424A(LNH-ST). Decreased sugar
      conversion and ethanol yield with increasing solids loading were also observed.
      End-product (ethanol) was proven to be the major cause of this issue and
      increased degradation products with increasing solids loading was also a cause.
      For the first time, we show that with in situ removal of end-product by
      performing SSCF aerobically, sugar conversion stopped decreasing with increasing
      solids loading and monomeric sugar conversion reached as high as 93% at a high
      solids loading of 24.9 wt%. Techno-economic analysis was employed to explore the
      economic possibilities of cellulosic ethanol production at high solids loadings.
      The results suggest that low-cost in situ removal of ethanol during SSCF would
      significantly improve the economics of high solids loading processes. Biotechnol.
      Bioeng. 2017;114: 980-989. (c) 2016 Wiley Periodicals, Inc.

PMID- 27888664
TI  - EBV-associated but HHV8-unrelated double-hit effusion-based lymphoma.
AB  - Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma
      presenting in effusion without a mass lesion. It shares many clinicopathological
      features with primary effusion lymphoma (PEL), but is distinct from PEL by the
      absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell
      lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often
      presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion.
      Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive
      ascites and left pleural effusion. He has no HIV, HBV or HCV infection and no
      mass lesion by CT scans. Cytology of both pleural effusion and ascites show large
      lymphoma cells with plasmablastic morphology characterized by pleomorphic and
      eccentric nuclei, prominent nucleoli and frequent mitoses. Immunohistochemical
      study with cell block shows that the lymphoma cells express plasma cell-related
      markers (CD138, MUM-1 and EMA), but not CD3, CD30, CD45, B-cell markers (CD19,
      CD20, CD79a, and PAX5), HHV8, ALK or cytokeratin. EBER is positive in most
      lymphoma cells. Fluorescence in situ hybridization reveals rearrangement at the
      IGH, BCL2, and MYC loci, but not at BCL6. It is diagnosed as an EBV-associated
      but HHV8-unrelated double hit effusion-based lymphoma with plasmablastic
      features. The patient passed away soon after diagnosis without chemotherapy. This
      is the first reported case of double-hit effusion-based lymphoma with MYC and
      BCL2 rearrangement. This case illustrates the importance of integrating clinical,
      cytological, immunophenotypical, and molecular findings to reach a correct
      diagnosis. Diagn. Cytopathol. 2017;45:257-261. (c) 2016 Wiley Periodicals, Inc.

PMID- 27888665
TI  - Bronchiolitis and asthma: the next step.

PMID- 27888666
TI  - Corrigendum to "Genetics, morphology and ecology reveal a cryptic pika lineage in
      the Sikkim Himalaya" [Mol. Phylogenet. Evol. 106 (2017) 55-60].

PMID- 27888668
TI  - Inflammatory Bowel Disease: A Global Disease That Needs a Broader Ensemble of
      Populations.

PMID- 27888667
TI  - Genetic Optimization of Liver Cancer Therapy: A Patient-Derived Primary Cancer
      Cell-Based Model.

PMID- 27888669
TI  - A Curmudgeon Reflects on Half a Century of Gastrointestinal Pathology.

PMID- 27888670
TI  - Endoscopic Findings in Eosinophilic Esophagitis and Esophageal Distensibility: A
      Proxy for Transmural Modeling?

PMID- 27888671
TI  - Sclerosing Polycystic Adenosis of the Parotid Gland: A Systematic Review and
      Report of 2 New Cases.
AB  - PURPOSE: We sought to evaluate clinical-epidemiologic aspects, pathologic
      characteristics, and treatment of sclerosing polycystic adenosis (SPA) of the
      parotid gland and to report 2 new cases. MATERIALS AND METHODS: We conducted a
      systematic review following PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) guidelines for studies published in or before June
      2016. The inclusion criteria were as follows: final diagnosis of SPA affecting
      the parotid gland and articles published in Spanish or English. The exclusion
      criteria were as follows: unclear diagnosis after pathologic analysis and
      patients affected by other conditions in the major salivary glands. We added 2
      new cases. RESULTS: Our review ultimately included 21 articles and 45 cases. The
      mean patient age was 41 years (range, 7-84 years). The female-to-male ratio was
      2:1. In all patients the tumor showed progressive growth. The evolution range was
      7 days to 11 years. In 17.7% of cases, the tumor was associated with pain. The
      average tumor size was 30.3 mm (range, 12-60 mm). Fine needle aspiration biopsy
      (FNAB) was unable to diagnose 30 cases. Benign tumors comprised 58% of tumors
      (18), whereas malignancy was present in 25.8% (8). Thirty-five tumors were well
      circumscribed. There were 8 multinodular or lobed cases. The tumor was described
      as encapsulated in 1 case, partially encapsulated or pseudo-encapsulated in 16,
      and not encapsulated in 12. Five cases showed different degrees of degenerative
      changes, ranging from dysplasia to invasive carcinoma. All cases underwent
      surgical treatment. Superficial parotidectomy with preservation of the facial
      nerve was performed in 22 cases (61.1%), total parotidectomy in 8 (22.2%), and
      tumor enucleation in 6 (16.6%). The mean follow-up period was 51.5 months (range,
      5-276 months). Of documented cases, 74.2% had 2 or more years of follow-up.
      Recurrences occurred in 6 cases (16.6%). CONCLUSIONS: We consider SPA a benign
      tumor with progressive growth, which is occasionally painful. It occurs around
      age 40 years and occurs more often in female patients. Fine needle aspiration
      biopsy does not provide an adequate preoperative diagnosis. Recurrences are
      infrequent. Follow-up should be customized according to the pathologic findings.
      Malignant transformation may occur. Superficial parotidectomy with facial nerve
      preservation is the treatment of choice.

PMID- 27888672
TI  - Incidence of coronary intervention in cardiac arrest survivors with non-shockable
      initial rhythms and no evidence of ST-elevation MI (STEMI).
AB  - OBJECTIVE: With the demonstrated benefit of an early-invasive strategy for STEMI
      and VF/VT arrest patients, there is interest in assessing the potential benefit
      of early angiography for non-shockable (PEA/Asystole) arrest patients. We
      hypothesized that in cardiac arrest patients who obtain return of spontaneous
      circulation (ROSC) after a non-shockable initial rhythm and do not have STEMI the
      incidence of coronary intervention would be clinically insignificant (<5%).
      METHODS: Retrospective multicenter US clinical registry study of post-cardiac
      arrest patients at 18 hospitals between 1/00 and 5/14. The incidence of
      significant coronary artery disease (CAD) as defined by documented coronary
      intervention (i.e. PCI, angioplasty, stent or CABG) was assessed. RESULTS: There
      were 1396 arrest patients with ROSC and known initial rhythms (517/1396=37%
      shockable; 879/1396=63% nonshockable). 440 (299/440=58% shockable; 141/440=32%
      nonshockable) of these patients received angiography. In the 141 non-shockable
      patients that received angiography, 97 patients did not have STEMI listed as an
      indication for catheterization and 24 (25%) of those had a coronary intervention
      documented yielding an observed incidence of coronary intervention in non
      shockable post-arrest patients without STEMI who received angiography of 24.7%
      (24/97). Of note, the overall incidence of coronary intervention in all ROSC
      patients with non-shockable initial rhythms was 5.5% (48/879). CONCLUSIONS: In
      this large multi-center retrospective analysis there is a high incidence of
      coronary intervention in post-arrest patients with initially non-shockable
      rhythms and without STEMI on ECG who are taken for angiography.

PMID- 27888673
TI  - Clinical correlates of pp65 antigenemia monitoring in the first months of post
      kidney transplant in patients undergoing universal prophylaxis or preemptive
      therapy.
AB  - INTRODUCTION: Human cytomegalovirus is a major cause of morbidity in kidney
      transplant patients. OBJECTIVES: We aimed to study viral replication and
      serological response in the first months post kidney transplant in patients
      undergoing universal prophylaxis or preemptive therapy and correlate the findings
      with the clinical course of Human cytomegalovirus infection. PATIENTS AND
      METHODS: Independent from the clinical strategy adopted for managing Human
      cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65
      antigenemia assay and serological response were assessed on the day of
      transplantation, and then weekly during the first three months of post
      transplant. RESULTS: From the 32 transplant recipients, 16 were positive for pp65
      antigenemia, with a similar incidence rate in each group. There were no positive
      results in the first three weeks of monitoring; the positivity rate peaked at
      week eight. There was a trend for a higher and earlier frequency of positivity in
      the universal prophylaxis group in which the course of the Human cytomegalovirus
      infection was also more severe. Despite the differences in clinical picture and
      in the initial immunosuppressant schedule, the serological response was similar
      in both groups. CONCLUSION: Routine monitoring during the first three post
      transplant months has a positive impact on the early detection of Human
      cytomegalovirus viral replication allowing for timely treatment in order to
      reduce morbidity of the disease. The strategy of universal therapy employing
      intravenous ganciclovir was associated to a worse clinical course of the Human
      cytomegalovirus infection suggesting that the use of >10 cells/2*105 leukocytes
      as a cut-off in this setting may be inappropriate.

PMID- 27888674
TI  - qPCR detection of Mycobacterium leprae in biopsies and slit skin smear of
      different leprosy clinical forms.
AB  - Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious
      disease that mainly affects the skin and peripheral nervous system. The diagnosis
      of leprosy is based on clinical evaluation, whereas histopathological analysis
      and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a
      current useful tool for diagnosis of infectious diseases, has been used to detect
      several pathogens including Mycobacterium leprae. The validation of this
      technique in a robust set of samples comprising the different clinical forms of
      leprosy is still necessary. Thus, in this study samples from 126 skin biopsies
      (collected from patients on all clinical forms and reactional states of leprosy)
      and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR
      (performed with primers for the RLEP region of M. leprae DNA) and routine
      bacilloscopy performed in histological sections or in slit skin smear.
      Considering clinical diagnostic as the gold standard, 84.9% of the leprosy
      patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity,
      with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values,
      respectively. Concerning bacilloscopy of histological sections (BI/H), the
      sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively.
      The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear,
      84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100%
      specificity, since all samples from different mycobacteria, from healthy
      individuals, and from other granulomatous diseases presented negative results. In
      conclusion, the qPCR technique for detection of M. leprae using RLEP primers
      proved to be specific and sensitive, and qPCR can be used as a complementary test
      to diagnose leprosy irrespective of the clinical form of disease.

PMID- 27888675
TI  - The antimicrobial peptide snakin-2 is upregulated in the defense response of
      tomatoes (Solanum lycopersicum) as part of the jasmonate-dependent signaling
      pathway.
AB  - Antimicrobial peptides (AMPs) are produced by all living organisms and play an
      important role in innate immunity because they are readily available and non
      specific against invading pathogenic microorganisms. Snakin-2 (SN2) from tomato
      is a short, cationic peptide that forms lethal pores in biomembranes of microbes.
      In plant cells, SN2 is produced as a prepeptide with a signal sequence for ER
      targeting and an acidic region to decrease toxicity in the producing organism.
      Gene expression analysis by qRT-PCR in tomato plants demonstrated that SN2 is
      constitutively expressed, mostly in leaves and flowers. After fungal infection,
      wounding, or external application of phytohormones (such as methyl jasmonate,
      MeJa) operating in the JA-dependent defense response, a systemic reaction with an
      elevated expression of the SN2 gene is triggered in all parts of tomato plants.
      Abiotic stress factors like extreme temperatures or dehydration do not affect SN2
      expression. Upon wounding, the expression of SN2 and LoxD are strongly enhanced
      in tomato fruits. Furthermore, we provide evidence that the protein level of
      bioactive SN2 is also increased upon application of methyl jasmonate in tomato
      seedlings.

PMID- 27888676
TI  - Revision surgery for cervical artificial disc: Surgical technique and clinical
      results.
AB  - OBJECTIVE: Cervical artificial disc replacement (C-ADR) was developed with the
      goal of preserving mobility of the cervical segment in patients with degenerative
      disc disease. So far, little is known about experiences with revision surgery and
      explantation of C-ADRs. Here, we report our experience with revision the third
      generation, Galileo-type disc prosthesis from a retrospective study of two
      institutions. PATIENTS AND METHODS: Between November 2008 and July 2016, 16
      patients with prior implantation of C-ADR underwent removal of the Galileo-type
      disc prosthesis (Signus, Medizintechnik, Germany) due to a call back by industry.
      In 10 patients C-ADR was replaced with an alternative prosthesis, 6 patients
      received an ACDF. Duration of surgery, time to revision, surgical procedure,
      complication rate, neurological status, histological findings and outcome were
      examined in two institutions. RESULTS: The C-ADR was successfully revised in all
      patients. Surgery was performed through the same anterior approach as the initial
      access. Duration of the procedure varied between 43 and 80min. Access-related
      complications included irritation of the recurrent nerve in one patient and mal
      positioning of the C-ADR in another patient. Follow up revealed two patients with
      permanent mild/moderate neurologic deficits, NDI (neck disability index) ranged
      between 10 and 42%. CONCLUSIONS: Anterior exposure of the cervical spine for
      explantation and revision of C-ADR performed through the initial approach has an
      overall complication rate of 18.75%. Replacements of the Galileo-type disc
      prosthesis with an alternative prosthesis or conversion to ACDF are both suitable
      surgical options without significant difference in outcome.

PMID- 27888677
TI  - Assessing positive emotional memories with peers: The Early Memories of Warmth
      and Safeness with Peers Scale for adolescents.
AB  - Research on the association between early positive relational experiences and
      later psychosocial adjustment is growing. The quality of peer relationships may
      have a particularly important effect on adolescents' wellbeing and mental health.
      The current study aimed at examining a measure of personal emotional memories of
      peer relationships characterized by warmth, safeness and affection, which
      occurred in childhood and adolescence (EMWSSPeers-A). Distinct samples (N = 584)
      of adolescents aged between 12 and 18 were used to assess the EMWSSPeers-A'
      factorial structure through a Principal Component Analysis and a Confirmatory
      Factor Analysis, and to analyse the scale's psychometric properties. Results
      indicated a one-dimensional structure with 12 items with very good internal
      consistency, and construct, convergent, divergent and incremental validities. By
      allowing the examination of the role played by memories of positive peer
      relationships on adolescents' psychological adjustment, the EMWSSPeers-A may be
      potentially useful for future model testing and for the assessment of
      interventions.

PMID- 27888678
TI  - Cerebral cortical neuron diversity and development at single-cell resolution.
AB  - Over a century of efforts to categorize the astonishing diversity of cortical
      neurons has relied on criteria of morphology, electrophysiology, ontology, and
      the expression of a few transcripts and proteins. The rapid development of single
      cell RNA sequencing (scRNA-seq) adds genome-wide gene expression patterns to this
      list of criteria, and promises to reveal new insights into the transitions that
      establish neuronal identity during development, differentiation, activity, and
      disease. Comparing single neuron data to reference atlases constructed from
      hundreds of thousands of single-cell transcriptomes will be critical to
      understanding these transitions and the molecular mechanisms that drive them. We
      review early efforts, and discuss future challenges and opportunities, in
      applying scRNA-seq to the elucidation of neuronal subtypes and their development.

PMID- 27888679
TI  - Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish
      population-based study from 2011 to 2014.
AB  - BACKGROUND: Human papillomavirus (HPV) is a critical element in the rising
      incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this
      trend will continue, and the types of HPV responsible, are currently unknown. We
      previously demonstrated an increased incidence of HPV-related OPSCC in the high
      HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we
      investigated if the incidence for OPSCC continued to rise, the association to HPV
      and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the
      expected incidence of OPSCC versus cervical cancer through to 2020. PATIENTS AND
      METHODS: Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base
      of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and
      Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re
      reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain
      reaction (PCR), with genotyping by next generation sequencing. RESULTS: Sixty-two
      percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate
      (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due
      to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-)
      OPSCC also increased during the study period. The majority of HPV+ tumours were
      HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%)
      and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. CONCLUSION:
      An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two
      percent of tumours were HPV+, which is a high-prevalence, although the lower
      number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype,
      although a significant proportion (14%) was of another genotype. Our projections
      suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016
      in Eastern Denmark.

PMID- 27888680
TI  - Symptomatic and functional outcomes of substance use disorder persistence 2 years
      after admission to a first-episode psychosis program.
AB  - Substance use disorders (SUD) in first-episode psychosis (FEP) are highly
      prevalent and linked with poor outcomes. However, most longitudinal studies
      investigating their impacts in FEP have not reported proportions of patients who
      ceased SUD. Our aim was to examine the influence of SUD course on functional and
      symptomatic outcomes as well as service use in FEP. We performed a 2-year
      longitudinal study of 212 FEP patients, aged between 18 and 30 years, admitted to
      2 early psychosis services in Montreal, Quebec, Canada. We observed that cannabis
      was the first substance abused (42.9% at baseline), followed by alcohol (19.3%).
      The SUD rate decreased by approximately 30% during the first year. Patients with
      persistent SUD had worse functional outcomes (Quality of Life Scale, Social and
      Occupational Functioning Assessment Scale, employment), more symptoms (Positive
      and Negative Symptoms Scale) and heavier service use (emergency and
      hospitalization). SUD persistence was associated with illness severity,
      homelessness and cluster-B personality. Those living with their parents and
      financially supported by them were more likely to cease SUD. Our results indicate
      that SUD course was more significant than having SUD at admission; persistent SUD
      was associated with worse outcomes. SUD decreased during a general early
      psychosis intervention program (with no specialized SUD treatment). An
      integrated, specialized approach targeting FEP patients with predictive factors
      of SUD persistence during the first years of treatment might increase SUD
      cessation and possibly improve outcomes.

PMID- 27888681
TI  - The buffer role of meaning in life in hopelessness in women with borderline
      personality disorders.
AB  - Meaning in life has been found to be a protective factor against suicidal
      ideation. The aim of this study was to investigate whether meaning in life can
      moderate and buffer the association between suicide risk factors and hopelessness
      in women with borderline personality disorders. One hundred twenty-four women
      diagnosed with borderline personality disorder completed self-report measures of
      suicide risk factors, hopelessness, and meaning in life. The main result from
      this study was that meaning in life moderated the association between suicide
      risk factors and hopelessness. Meaning in life is an important variable in the
      prevention and treatment of risk of suicide in women with borderline personality
      disorder.

PMID- 27888682
TI  - Affective temperaments, as measured by TEMPS-A, among self-poisoning nonlethal
      suicide attempters.
AB  - Suicidal behaviors are serious public health problems. The prominent association
      of mood disorders with suicide, along with the renaissance of the spectrum
      concept of psychiatric disorders in the recent decades, prioritizes the
      investigation of temperament variants in suicidal individuals. This study aimed
      to explore the relationship between affective temperaments and nonviolent suicide
      attempts. We administered Temperament Evaluation of the Memphis, Pisa, Paris, and
      San Diego Auto questionnaire (TEMPS-A) to 141 (27 males and 114 females)
      consecutive self-poisoning non-lethal suicide attempters at a Medical Toxicology
      Center and a sex and age matched group of healthy individuals (28 males, 112
      females). Female suicide attempters scored significantly higher in depressive,
      cyclothymic, irritable, and anxious temperaments compared with female controls,
      whereas male cases' scores were significantly higher in depressive and anxious
      subscales compared with control males. Except for hyperthymic temperament which
      did not reveal any significant effects, depressive (OR: 11.5), cyclothymic (OR:
      3.8), irritable (OR: 2.3), and anxious (OR: 8.8) temperaments were predictors for
      nonviolent suicide attempts. Therefore, this study replicated the evidence for
      the strong association of depressive temperament with suicide attempts. The
      hyperthymic temperament appeared to have neither protective nor predisposing
      influence. Further studies are needed to identify the role of this independent
      temperament.

PMID- 27888684
TI  - Ultrasensitive non enzymatic multiple immunosensor for tumor markers detection by
      coupling DNA hybridization chain reaction with intercalated molecules.
AB  - In this study, we tried coupling the small signal molecules that could
      intercalate into DNA double helix with hybridization chain reaction (HCR)
      technique to fabricate a multiple immunosensor. Doxorubicin hydrochloride (DXH)
      and methylene blue (MB) were used as signal molecules and alpha-fetoprotein (AFP)
      and carcinoembryonic antigen (CEA) were selected as model biomarkers. The
      immunosensor mainly consists of three parts as follows: First, two different
      primary antibodies (Ab1) immobilized on the surface of gold nanoparticles (Au
      NPs); Second, secondary antibodies (Ab2) conjugated with DNA primer; Third, long
      DNA concatemers from HCR were used as a carrier to intercalate amounts of signal
      molecules (DXH or MB). A sandwich immunocomplex was formed among primary
      antibodies, target biomarkers and secondary antibodies conjugated with DNA primer
      via specific recognition reaction. Afterwards, DNA concatemers intercalating
      amounts of DXH or MB were linked to DNA primer via DNA hybridization. Square wave
      voltammetry (SWV) was employed to record the response signals from electroactive
      molecules DXH and MB, and two distinguishable signals were obtained, which peak
      potentials were at about -0.30V (corresponding to MB) and -0.70V (corresponding
      to DXH, both vs SCE), respectively. The signal intensities of MB and DXH were
      linearly related to the logarithm of biomarkers concentration in the range of
      0.05pgmL-1-25ngmL-1, and the limit of detection were 0.03pgmL-1 for CEA and
      0.02pgmL-1 for AFP (at S/N=3), respectively. Furthermore, the immunosensor
      exhibited a sensitive electrochemical response to biomarkers in human serum
      samples and the results obtained were in accordance with reference method,
      indicating the immunosensor can be applied to real sample analysis in clinic
      diagnosis.

PMID- 27888685
TI  - Label-free piezoelectric biosensor for prognosis and diagnosis of Systemic Lupus
      Erythematosus.
AB  - An autoantigen piezoelectric sensor to quantify specific circulating
      autoantibodies in human serum is developed. The sensor consisted on a quartz
      crystal microbalance with dissipation monitoring (QCM-D) where TRIM21 and TROVE2
      autoantigens were covalently immobilized, allowing the selective determination of
      autoantibodies for diagnosis and prognosis of Systemic Lupus Erythematosus (SLE).
      The sensitivity of the biosensor, measured as IC50 value, was 1.51U/mL and
      0.32U/mL, for anti-TRIM21 and anti-TROVE2 circulating autoantibodies,
      respectively. The sensor is also able to establish a structural interaction
      fingerprint pattern or profile of circulating autoantibodies, what allows scoring
      accurately SLE patients. Furthermore, a statistical association of global disease
      activity with TRIM21-TROVE2 interaction was found (n=130 lupic patient samples, p
      value=0.0413). The performances of the biosensor were compared with standard
      ELISA and multiplex DVD-array high-throughput screening assays, corroborating the
      viability of piezoelectric biosensor as a cost-effective in vitro assay for the
      early detection, monitoring or treatment of rare diseases.

PMID- 27888686
TI  - Integration of isothermal amplification methods in microfluidic devices: Recent
      advances.
AB  - The integration of nucleic acids detection assays in microfluidic devices
      represents a highly promising approach for the development of convenient, cheap
      and efficient diagnostic tools for clinical, food safety and environmental
      monitoring applications. Such tools are expected to operate at the point-of-care
      and in resource-limited settings. The amplification of the target nucleic acid
      sequence represents a key step for the development of sensitive detection
      protocols. The integration in microfluidic devices of the most popular technology
      for nucleic acids amplifications, polymerase chain reaction (PCR), is
      significantly limited by the thermal cycling needed to obtain the target sequence
      amplification. This review provides an overview of recent advances in integration
      of isothermal amplification methods in microfluidic devices. Isothermal methods,
      that operate at constant temperature, have emerged as promising alternative to
      PCR and greatly simplify the implementation of amplification methods in point-of
      care diagnostic devices and devices to be used in resource-limited settings.
      Possibilities offered by isothermal methods for digital droplet amplification are
      discussed.

PMID- 27888683
TI  - Lifetime antipsychotic medication and cognitive performance in schizophrenia at
      age 43 years in a general population birth cohort.
AB  - This naturalistic study analysed the association between cumulative lifetime
      antipsychotic dose and cognition in schizophrenia after an average of 16.5 years
      of illness. Sixty participants with schizophrenia and 191 controls from the
      Northern Finland Birth Cohort 1966 were assessed at age 43 years with a
      neurocognitive test battery. Cumulative lifetime antipsychotic dose-years were
      collected from medical records and interviews. The association between
      antipsychotic dose-years and a cognitive composite score based on principal
      component analysis was analysed using linear regression. Higher lifetime
      antipsychotic dose-years were significantly associated with poorer cognitive
      composite score, when adjusted for gender, onset age and lifetime hospital
      treatment days. The effects of typical and atypical antipsychotics did not
      differ. This is the first report of an association between cumulative lifetime
      antipsychotic dose and global cognition in midlife schizophrenia. Based on these
      data, higher lifetime antipsychotic dose-years may be associated with poorer
      cognitive performance at age 43 years. Potential biases related to the
      naturalistic design may partly explain the results; nonetheless, it is possible
      that large antipsychotic doses harm cognition in schizophrenia in the long-term.

PMID- 27888687
TI  - Accurate quantitation of choline and ethanolamine plasmalogen molecular species
      in human plasma by liquid chromatography-tandem mass spectrometry.
AB  - Concentration of both choline plasmalogen (PC-Pls) and ethanolamine Pls (PE-Pls)
      in human plasma/serum has been getting attention to, since certain patients
      including those with neurodegenerative disorders, have been reported to exhibit
      reduced levels of specific Pls species. However, despite using liquid
      chromatography-tandem mass spectrometry (LC-MS/MS), accurate quantitation of Pls
      is still difficult because of less product ion from PC-Pls and quantitative
      issues (e.g., extraction recoveries and matrix effects). The present study aimed
      to develop a method for accurate identification and quantitation of Pls molecular
      species using LC-MS/MS operated in the multiple reaction monitoring mode. The LC
      MS/MS conditions in the presence of sodium, and the extraction method using
      methanol protein precipitation were optimized. Under the optimal condition, Pls
      was detected at femtomole levels. The recoveries of Pls from human plasma were
      nearly 100%, and matrix effects were not observed. The novel method enabled
      determination of each Pls species in human plasma at the concentrations of 0.5
      13.6MUM. Then the PC-Pls and PE-Pls species in the plasma of both healthy
      subjects and patients with Alzheimer's disease were quantitated. The method
      developed herein represents a powerful tool for analyzing Pls, which may provide
      a better understanding of their physiological roles in vivo.

PMID- 27888689
TI  - Negotiating and valuing spaces: The discourse of space and 'home' in care homes.
AB  - This paper examines how space in care homes is experienced and negotiated by
      people who live and work in them. The analysis of qualitative data of five in
      depth case studies of care homes in England revealed three key ways in which
      space is negotiated: a) the way in which values affect interactions inside versus
      outside the care home environment, b) the negotiation of boundaries and domains
      within the homes, and c) the sense of being at 'home'. The paper illuminates how
      the design of the buildings and organisational factors can reinforce or bridge
      dichotomies between inside and outside spaces. Residents' abilities to re
      negotiate boundaries, domains and communal spaces within homes are shown to be
      affected by organisational factors such as priorities of staff members. Despite
      'home' being a common discourse, the spaces within care homes were often
      organised, ordered and experienced as two distinct, co-present worlds: the
      dwelling place of residents and the workplace of staff.

PMID- 27888690
TI  - Exploring socioeconomic differences in syntactic development through the lens of
      real-time processing.
AB  - Differences in caregiver input across socioeconomic status (SES) predict
      syntactic development, but the mechanisms are not well understood. Input effects
      may reflect the exposure needed to acquire syntactic representations during
      learning (e.g., does the child have the relevant structures for passive
      sentences?) or access this knowledge during communication (e.g., can she use the
      past participle to infer the meaning of passives?). Using an eye-tracking and act
      out paradigm, the current study distinguishes these mechanisms by comparing the
      interpretation of actives and passives in 3- to 7-year-olds (n=129) from varying
      SES backgrounds. During the presentation of spoken sentences, fixations revealed
      robust disambiguation of constructions by children from higher-SES backgrounds,
      but less sensitivity by lower-SES counterparts. After sentence presentation,
      decreased sensitivity generated interpretive challenges and average SES-related
      differences for passives requiring syntactic revision ("The seal is quickly eaten
      by it"). Critically, no differences were found when revision was not needed ("It
      is quickly eaten by the seal"). These results suggest that all children shared an
      ability to acquire passives, but SES-related differences in real-time processing
      can impact the accuracy of utterance interpretation.

PMID- 27888688
TI  - An oral HemokineTM, alpha-methylhydrocinnamate, enhances myeloid and neutrophil
      recovery following irradiation in vivo.
AB  - An oral therapeutic which reduces duration of cytopenias and is active following
      accidental radiation exposures is an unmet need in radiation countermeasures.
      Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth
      factor dependency of multi-lineage cell lines, and stimulates erythropoiesis.
      Here, ST7 and its isomers were studied for their effects on myeloid progenitors
      and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates,
      and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM
      production by 1.7-fold (p<0.001), reduced neutrophil apoptosis comparable to G
      CSF, and enhanced HSC survival post-radiation by 2-fold, (p=0.028). ST7 and ST7-S
      administered in normal baboons increased ANC and platelet counts by 50-400%. In
      sub-lethally-irradiated mice, ANC nadir remained >200/mm3 and neutropenia
      recovered in 6days with ST7 treatment and 18days in controls (p<0.05). In
      lethally-irradiated mice, marrow pathology at 15days was hypocellular (10%
      cellularity) in controls, but normal (55-75% cellularity) with complete
      neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7,
      given orally for 4days, reduced mortality, with 30% survival in ST7-animals vs 8%
      in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S
      enhance myeloid recovery post-radiation and merit further evaluation to
      accelerate hematologic recovery in conditions of radiation-related and other
      marrow hypoplasias.

PMID- 27888693
TI  - Children's judgments about ownership rights and body rights: Evidence for a
      common basis.
AB  - We report two experiments supporting the theory that children's understanding of
      ownership rights is related to their notions of body rights. Experiment 1
      investigated 4- to 7-year-olds' (N=123) developing sensitivity to physical
      contact in their judgments about the acceptability of behaving in relation to
      owned objects and body parts. Experiment 2 used a simpler design to investigate
      this in 3- and 4-year-olds (N=112). Findings confirmed two predictions of the
      theory. First, in both experiments, children's judgments about ownership and body
      rights were similarly affected by physical contact. Second, judgments about both
      kinds of rights were yoked in development; age-related changes in judgments about
      ownership rights were paralleled by changes in judgments about body rights. Our
      findings have additional import for theories of ownership rights because they
      suggest that physical contact may be a crucial factor in whether behaviors
      targeting property are judged to be permissible.

PMID- 27888692
TI  - Mitochondrial GSH replenishment as a potential therapeutic approach for Niemann
      Pick type C disease.
AB  - Niemann Pick type C (NPC) disease is a progressive lysosomal storage disorder
      caused by mutations in genes encoding NPC1/NPC2 proteins, characterized by
      neurological defects, hepatosplenomegaly and premature death. While the primary
      biochemical feature of NPC disease is the intracellular accumulation of
      cholesterol and gangliosides, predominantly in endolysosomes, mitochondrial
      cholesterol accumulation has also been reported. As accumulation of cholesterol
      in mitochondria is known to impair the transport of GSH into mitochondria,
      resulting in mitochondrial GSH (mGSH) depletion, we investigated the impact of
      mGSH recovery in NPC disease. We show that GSH ethyl ester (GSH-EE), but not N
      acetylcysteine (NAC), restored the mGSH pool in liver and brain of Npc1-/- mice
      and in fibroblasts from NPC patients, while both GSH-EE and NAC increased total
      GSH levels. GSH-EE but not NAC increased the median survival and maximal life
      span of Npc1-/- mice. Moreover, intraperitoneal therapy with GSH-EE protected
      against oxidative stress and oxidant-induced cell death, restored calbindin
      levels in cerebellar Purkinje cells and reversed locomotor impairment in Npc1-/-
      mice. High-resolution respirometry analyses revealed that GSH-EE improved
      oxidative phosphorylation, coupled respiration and maximal electron transfer in
      cerebellum of Npc1-/- mice. Lipidomic analyses showed that GSH-EE treatment had
      not effect in the profile of most sphingolipids in liver and brain, except for
      some particular species in brain of Npc1-/- mice. These findings indicate that
      the specific replenishment of mGSH may be a potential promising therapy for NPC
      disease, worth exploring alone or in combination with other options.

PMID- 27888691
TI  - Redox imbalance and mitochondrial abnormalities in the diabetic lung.
AB  - Although the lung is one of the least studied organs in diabetes, increasing
      evidence indicates that it is an inevitable target of diabetic complications.
      Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes
      remain largely unexplored. Given that redox imbalance, oxidative stress, and
      mitochondrial dysfunction have been implicated in diabetic tissue injury, we set
      out to investigate mechanisms of lung injury in diabetes. The objective of this
      study was to evaluate NADH/NAD+ redox status, oxidative stress, and mitochondrial
      abnormalities in the diabetic lung. Using STZ induced diabetes in rat as a model,
      we measured redox-imbalance related parameters including aldose reductase
      activity, level of poly ADP ribose polymerase (PAPR-1), NAD+ content, NADPH
      content, reduced form of glutathione (GSH), and glucose 6-phophate dehydrogenase
      (G6PD) activity. For assessment of mitochondrial abnormalities in the diabetic
      lung, we measured the activities of mitochondrial electron transport chain
      complexes I to IV and complex V as well as dihydrolipoamide dehydrogenase (DLDH)
      content and activity. We also measured the protein content of NAD+ dependent
      enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1).
      Our results demonstrate that NADH/NAD+ redox imbalance occurs in the diabetic
      lung. This redox imbalance upregulates the activities of complexes I to IV, but
      not complex V; and this upregulation is likely the source of increased
      mitochondrial ROS production, oxidative stress, and cell death in the diabetic
      lung. These results, together with the findings that the protein contents of
      DLDH, sirt3, and NQO1 all are decreased in the diabetic lung, demonstrate that
      redox imbalance, mitochondrial abnormality, and oxidative stress contribute to
      lung injury in diabetes.

PMID- 27888694
TI  - Head movement measurement: An alternative method for posturography studies.
AB  - The present study evaluated the measurement of head movements as a valid method
      for postural emotional studies using the comparison of simultaneous recording of
      center of pressure (COP) sway as criterion. Thirty female students viewed a set
      of 12 pleasant, 12 unpleasant and 12 neutral pictures from the International
      Affective Picture System, repeated twice, using a block presentation procedure
      while standing on a force platform (AMTI AccuSway). Head movements were recorded
      using a webcam ((c)KPC139E) located in the ceiling in line with the force
      platform and a light-emitting diode (LED) placed on the top of the head. Open
      source software (CvMob 3.1) was used to process the data. High indices of
      correlation and coherence between head and COP sway were observed. In addition,
      pleasant pictures, compared with unpleasant pictures, elicited greater body sway
      in the anterior-posterior axis, suggesting an approach response to appetitive
      stimuli. Thus, the measurement of head movement can be an alternative or
      complementary method to recording COP for studying human postural changes.

PMID- 27888696
TI  - Underwater gait analysis in Parkinson's disease.
AB  - Although hydrotherapy is one of the physical therapies adopted to optimize gait
      rehabilitation in people with Parkinson disease, the quantitative measurement of
      gait-related outcomes has not been provided yet. This work aims to document the
      gait improvements in a group of parkinsonians after a hydrotherapy program
      through 2D and 3D underwater and on land gait analysis. Thirty-four parkinsonians
      and twenty-two controls were enrolled, divided into two different cohorts. In the
      first one, 2 groups of patients underwent underwater or land based walking
      training; controls underwent underwater walking training. Hence pre-treatment 2D
      underwater and on land gait analysis were performed, together with post-treatment
      on land gait analysis. Considering that current literature documented a reduced
      movement amplitude in parkinsonians across all lower limb joints in all movement
      planes, 3D underwater and on land gait analysis were performed on a second cohort
      of subjects (10 parkinsonians and 10 controls) who underwent underwater gait
      training. Baseline land 2D and 3D gait analysis in parkinsonians showed shorter
      stride length and slower speed than controls, in agreement with previous
      findings. Comparison between underwater and on land gait analysis showed
      reduction in stride length, cadence and speed on both parkinsonians and controls.
      Although patients who underwent underwater treatment exhibited significant
      changes on spatiotemporal parameters and sagittal plane lower limb kinematics, 3D
      gait analysis documented a significant (p<0.05) improvement in all movement
      planes. These data deserve attention for research directions promoting the
      optimal recovery and maintenance of walking ability.

PMID- 27888695
TI  - Automatic identification of gait events during walking on uneven surfaces.
AB  - The accurate detection of gait events is essential for clinical gait analysis.
      Aside from speed, surface characteristics like planarity and compliance can
      affect gait kinematics. Therefore detection of kinematic gait events on uneven
      surfaces may be inaccurate. To date, no study has investigated the possible
      influence of surface characteristics on gait event detection. Thus, the purpose
      of this study was to assess and compare the performance of four kinematic-based
      gait event detection algorithms (horizontal heel-heel displacement, foot
      velocity, heel/toe-PSIS displacement, peak hip extension) during walking on three
      surfaces with different degrees of planarity. Kinematic and force plate data were
      collected on thirteen athletes during two self-selected walking speeds at a
      normal (1.30+/-0.03m/s) and fast pace (1.70+/-0.10m/s). Footstrike and toe-off
      events were calculated by the algorithms and compared to vertical ground reaction
      force as a reference. The main findings of the study were: (1) surface
      configuration had an effect on algorithm accuracy (p<0.010, 0.84<d<2.79); (2) the
      vertical foot-velocity profile provided the lowest RMSE for footstrike (8.8
      14.6ms) during normal walking and toe-off (15.4-24.9ms) during normal and fast
      walking on all surfaces; (3) horizontal heel-ankle displacement provided the
      lowest RMSE for footstrike during fast walking on all surfaces (RMSE: 8.9
      13.8ms). Overall, the vertical foot-velocity algorithm provided low RMSE for all
      conditions, is easy to apply and thus recommended for gait event detection.

PMID- 27888697
TI  - Whole body organization during a symmetric bimanual pick up task in overweight
      and obese children.
AB  - Information on the effects of obesity on the biomechanics of whole body movement
      control in children is limited. The purpose of the current study is to test the
      hypothesis that during a simple pick up task, overweight and obese children will
      organize their whole body movements differently than those in normal weight
      children. Twelve children who were overweight or obese (5-13 years old) and
      twelve age matched normal weight children participated in the study. Children
      picked up an empty box to waist height at a self-selected pace while kinematic
      and kinetic data were recorded and analyzed using a VICON system and two AMTI
      force plates. The overweight and obese group showed less knee flexion in both
      legs, more spine flexion, and less excursion in the height of their center of
      mass (all Ps<0.05). However, the overweight and obese group had more anterior
      movement in their center of mass (P<0.05). For the center of pressure findings,
      the overweight and obese group had greater anterior excursion with faster average
      anterior moving speed and spent a longer time with the center of pressure reached
      forward (all Ps<0.05). These findings indicate that overweight and obese children
      organize their whole body movement during a simple pick up task differently with
      higher and more forward center of mass, quickly shifting their center of pressure
      anteriorly, and with a longer period of time with the center of pressure
      remaining forward. Their movement strategy may put them in a less stable
      condition and thus make them prone to losing balance.

PMID- 27888698
TI  - Sustained fecal-oral human-to-human transmission following a zoonotic event.
AB  - Bacterial, viral and parasitic zoonotic pathogens that transmit via the fecal
      oral route have a major impact on global health. However, the mechanisms
      underlying the emergence of such pathogens from the animal reservoir and their
      persistence in the human population are poorly understood. Here, we present a
      framework of human-to-human transmission of zoonotic pathogens that considers the
      factors relevant for fecal-oral human-to-human transmission route at the levels
      of host, pathogen, and environment. We discuss current data gaps and propose
      future research directions.

PMID- 27888699
TI  - Tumor detection using magnetosome nanoparticles functionalized with a newly
      screened EGFR/HER2 targeting peptide.
AB  - A novel peptide (P75) targeting EGFR and HER2 is successfully screened from a one
      bead-one-compound (OBOC) library containing approximately 2 * 105 peptides built
      with the aid of computational simulation. In vitro and in vivo analyses show that
      P75 binds to human epithelial growth factor receptor (EGFR) with nanomolar
      affinity and to epithelial growth factor receptor-2 (HER2) with a lower affinity
      but comparable to other reported peptides. The peptide is used to modify the
      surface of magnetosome nanoparticles (NPs) for targeted magnetic resonance
      imaging (MRI). In vitro and in vivo fluorescence imaging results suggest peptide
      P75 modified magnetosomes (Mag-P75) specifically bind to MDA-MB-468 and SKBR3
      cells as well as xenograft tumors with surprisingly low accumulation in other
      organs including liver and kidney. In vivo T2-weighted MR imaging studies of the
      xenograft tumors from SKBR3 and MDA-MB-468 cells show obviously negative contrast
      enhancement. The high affinity and specificity of P75 to EGFR and HER2 positive
      tumors, together with the success of peptide functionalized magnetosome NPs for
      targeted MRI demonstrate the potential of this peptide being used in the EGFR and
      HER2 positive tumors diagnosis and therapy.

PMID- 27888700
TI  - Negative mood and interference control in nonsuicidal self-injury.
AB  - People who engage in nonsuicidal self-injury (NSSI) often report high levels of
      impulsivity. However, results from behavioral tasks measuring impulsivity have
      been mixed: those with a history of NSSI generally perform comparably to healthy
      controls. Recent research suggests, however, that people who self-injure have
      specific deficits in response inhibition to negative emotional stimuli. Here, we
      extend this work by testing whether negative mood impairs interference control in
      NSSI. 33 participants reporting a history of NSSI (approximately half in the past
      year) and 31 age- and gender-matched healthy controls completed the multi-source
      interference task before and after a written negative mood induction designed to
      increase feelings of worthlessness, guilt, and shame. After the induction, the
      NSSI group reported increased negative mood but did not show worse interference
      control. In other words, increased negative mood did not correspond to increased
      behavioral impulsivity in participants reporting NSSI. Consistent with past
      research, the NSSI and healthy control groups showed equivalent task performance.
      This study adds to evidence that NSSI is not characterized by behavioral
      impulsivity, even in the context of negative mood.

PMID- 27888701
TI  - Inactivation of urease by catechol: Kinetics and structure.
AB  - Urease is a Ni(II)-containing enzyme that catalyzes the hydrolysis of urea to
      yield ammonia and carbamate at a rate 1015 times higher than the uncatalyzed
      reaction. Urease is a virulence factor of several human pathogens, in addition to
      decreasing the efficiency of soil organic nitrogen fertilization. Therefore,
      efficient urease inhibitors are actively sought. In this study, we describe a
      molecular characterization of the interaction between urease from Sporosarcina
      pasteurii (SPU) and Canavalia ensiformis (jack bean, JBU) with catechol, a model
      polyphenol. In particular, catechol irreversibly inactivates both SPU and JBU
      with a complex radical-based autocatalytic multistep mechanism. The crystal
      structure of the SPU-catechol complex, determined at 1.50A resolution, reveals
      the structural details of the enzyme inhibition.

PMID- 27888702
TI  - Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A
      comparative study of 400 cases.
AB  - OBJECTIVE: We sought to evaluate the global success rate of intramuscular
      methotrexate for the treatment of ectopic pregnancy, identify factors predictive
      of treatment success or failure, and study methotrexate tolerability in a large
      patient cohort. STUDY DESIGN: For this single-center retrospective observational
      study, we retrieved the records of all women who had a clinically or
      echographically confirmed ectopic pregnancy with a Fernandez score <13 and who
      were treated according to a 1mg/kg intramuscular single-dose methotrexate
      protocol. Medical treatment failure was defined by an obligation to proceed to
      laparoscopy. Needing a second injection was not considered to be medical
      treatment failure. RESULTS: Between February 2008 and November 2013 (69 months),
      400 women received methotrexate for ectopic pregnancy. The medical treatment
      protocol was effective for 314 patients, i.e., an overall success rate of 78.5%.
      A single methotrexate dose was sufficient for 63.5% of the women and a second
      dose was successful for 73.2% of the remaining women. The medical treatment
      success rate fell as initial hCG levels climbed. The main factors associated with
      methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic
      blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics
      of hCG levels was predictive of success. Methotrexate treatment was successful in
      90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with
      only 9% of the women reporting non-severe adverse effects. The fertility rate
      with delivery after medical treatment for ectopic pregnancy was 80.7%.
      CONCLUSION: In this study, we showed that an initial hCG value <1000IU/l and
      favorable early HCG kinetics were predictive factors for the successful medical
      treatment of ectopic pregnancy by methotrexate, and hematosalpinx and
      pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its
      failure. We also confirmed good tolerability for single-dose methotrexate
      protocols.

PMID- 27888703
TI  - The association between prenatal atrioventricular septal defects and chromosomal
      abnormalities.
AB  - OBJECTIVE: Atrioventricular septal defect is associated with a high risk of a
      chromosomal abnormality, particularly trisomy 21. The aim of this study is to
      assess the rate of trisomy 21 in fetuses diagnosed with an atrioventricular
      septal defect and to examine the influence of prior screening on the rate of
      trisomy 21. METHODS: Electronic ultrasound database was searched to identify
      fetuses diagnoses with an atrioventricular septal defect from 2002 to 2014. Rate
      of trisomy 21 and other aneuploidies was calculated among fetuses with normal
      situs. The prevalence of trisomy 21 and other aneuploidies was assessed in women
      with low and high first trimester risk for trisomy 21, using a cut-off value of
      1:150 and 1:250. RESULTS: A total 110 fetuses with a diagnosis of
      atrioventricular septal defect were identified. Among the 98 fetuses with normal
      situs, the prevalence of trisomy 21 was 46% (95% CI: 36-56%). Using a 1:150
      threshold, the rate of trisomy 21 within the low-risk group was 41% (95% CI: 27
      57%) while in the high-risk group it was 70% (95% CI: 52-83%), significantly
      higher than in the low risk group (p=0.028). Similar results were obtained when
      the 1:250 threshold was applied (66% versus 41%, p=0.055). CONCLUSIONS: The rate
      of trisomy 21 among fetuses identified with an atrioventricular septal defect in
      the second trimester is high even in those that undergo first trimester combined
      screening. Some fetuses with a high-risk screening result show a normal
      karyotype. Therefore, an offer of an invasive procedure to check fetal
      karyotyping is indicated. Knowledge of these rates may be helpful for parents in
      the decision making process.

PMID- 27888705
TI  - Chemotherapy-related leukopenia as a biomarker predicting survival outcomes in
      locally advanced cervical cancer.
AB  - OBJECTIVE: To investigate the impact of hematologic toxicity and leukopenia in
      locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy
      (NACT). STUDY DESIGN: Data of consecutive patients undergoing platinum-based NACT
      followed by surgery were retrospectively searched in order to evaluate the impact
      of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per
      the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival
      outcomes were evaluated using Kaplan-Meir and Cox hazard models. RESULTS:
      Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced
      grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in
      11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12
      57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate
      analysis, no factor was independently associated with disease-free survival;
      while a trend toward worse prognosis was observed for patients experiencing
      grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly,
      grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity
      (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81
      (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate
      analysis. Magnitude of leukopenia correlated with survival (p<0.001).
      CONCLUSIONS: Although, our data have to be confirmed by prospective
      investigations, the present study shows an association between the occurrence of
      leukopenia and survival outcomes. NACT-related immunosuppression might reduce the
      response against the tumor, thus promoting cancer progression.

PMID- 27888704
TI  - Association of R156R single nucleotide polymorphism of the ERCC2 gene with the
      susceptibility to ovarian cancer.
AB  - AIM: The reported study was designed to explore associations between the ERCC2-
      R156R gene single nucleotide polymorphism (SNP) and the risk of ovarian cancer.
      MATERIAL AND METHODS: The R156R (C to A, rs238406) polymorphism of ERCC2 gene was
      investigated by the PCR-RFLP technique in 400 patients with ovarian carcinoma and
      400 age- and sex matched non-cancer controls. Blood samples were obtained from
      patients treated at the Department of Surgical Gynaecology and Gynaecologic
      Oncology, Institute of Polish Mothers Memorial Hospital between the years 2000
      and 2015. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated
      for each genotype and allele. RESULTS: Genotype distribution of R156R
      polymorphism of ERCC2 gene was compared between the patients and controls with
      significant differences (p<0.05) between the two investigated groups. A possible
      association was observed between ovarian cancer and the presence of A/A genotype
      (OR 3.30 95% CI 2.26-4.82, p<0.0001). The variant A allele of ERCC2 increased the
      risk of ovarian cancer (OR 2.08 95 % CI 1.70-2.54, p<0.0001). A relationship was
      confirmed between ERCC2 R156R polymorphism and ovarian cancer progression,
      assessed by the degree of histological grades and FIGO staging (p<0.05).
      CONCLUSION: This is the first study, linking R156R polymorphism of ERCC2 gene
      with ovarian carcinoma incidence. In conclusion, ERCC2- R156R polymorphism may be
      connected with the susceptibility to ovarian cancer.

PMID- 27888706
TI  - Position for labor and birth: State of knowledge and biomechanical perspectives.
AB  - This review aims to examine how childbirth position during labour affects
      maternal, fetal and neonatal outcomes. Epidemiological data suggest that vertical
      birthing positions have many benefits. But when we consider the players and
      mechanisms of delivery, including the forces generated to move the fetus and
      obstacles to its progression, many questions remain about the advantage of one
      position over another. Thus, childbirth could be considered in a way as an
      athletic feat that probably requires the choice of optimal positions. These
      should be individually suited to each woman at different stage of labour to
      improve its efficiency and effectiveness. Tweetable abstract: Beyond
      epidemiological data, biomechanical investigations is necessary to assess birth's
      position.

PMID- 27888707
TI  - Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is
      Associated With Poor Prognosis Via EMT.
AB  - Triple-negative breast cancer (TNBC) was regarded as the most aggressive and
      mortal subtype of breast cancer (BC) since the molecular subtype system has been
      established. Abundant studies have revealed that epithelial-mesenchymal
      transition (EMT) played a pivotal role during breast cancer metastasis and
      progression, especially in TNBC. Herein, we showed that inhibition the expression
      of replication factor C subunit 3 (RFC3) significantly attenuated TNBC metastasis
      and progression, which was associated with EMT signal pathway. In TNBC cells,
      knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate
      epithelial markers, significantly attenuated cell proliferation, migration and
      invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor
      volume, weight and relieve lung metastasis in vivo. Furthermore, we also
      demonstrated that overexpression of RFC3 in TNBC showed increased metastasis,
      progression and poor prognosis. We confirmed all of these results by
      immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3
      expression was significantly associated with poor prognosis in TNBC. Taken all
      these findings into consideration, we can conclude that up-regulation of RFC3
      promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an
      independent prognostic factor and therapeutic target for TNBC.

PMID- 27888708
TI  - Prognostic Value of Tumor-Infiltrating Lymphocytes for Patients With Head and
      Neck Squamous Cell Carcinoma.
AB  - BACKGROUND: The prognostic value of tumor-infiltrating lymphocytes (TILs) in head
      and neck squamous cell carcinoma (HNSCC) remains controversial. Additionally,
      there is no standardized approach or cutoff value for evaluating TIL levels. The
      aim of this study was to establish a feasible method and criterion to assess TIL
      levels for future clinical practice and research use and to explore the
      relationship between TIL levels and prognosis. PATIENTS AND METHODS: This
      retrospective cohort study reviewed the records and pathological sections of 202
      patients with HNSCC who were surgically treated at Beijing Stomatological
      Hospital, Capital Medical University, from January 1998 to January 2011. The
      predictor variable was the TIL level. The main outcome assessment parameters were
      disease-free survival (DFS) and disease-specific survival (DSS). RESULT: The T
      stage (P = .008), smoking history (P = .042), alcohol history (P = .048), need
      for radiotherapy (P = .012) and microscopic extracapsular spread (ECS) (P = .012)
      were associated with the TIL level. A cutoff value equal to 70% could be taken as
      a threshold for TIL assessment, with a TIL level higher than 70% associated with
      a better prognosis (DFS rate: 51.9%, P = .018; DSS rate: 59.3%, P = .049). The
      Cox regression model showed that the TIL level was an independent prognostic
      factor for DFS (hazard ratio (HR): 0.786, 95% CI: 0.618-0.999, P = .049).
      CONCLUSION: The TIL level is closely related to the prognosis of patients with
      HNSCC. A threshold value of 70% is appropriate for TIL assessment, as patients
      with a TIL level higher than 70% show a better prognosis. Thus, the TIL level
      might serve as an independent predictor for HNSCC recurrence.

PMID- 27888709
TI  - Correlations Between DCE MRI and Histopathological Parameters in Head and Neck
      Squamous Cell Carcinoma.
AB  - BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) can
      characterize perfusion and vascularization of tissues. DCE MRI parameters can
      differentiate between malignant and benign lesions and predict tumor grading. The
      purpose of this study was to correlate DCE MRI findings and various
      histopathological parameters in head and neck squamous cell carcinoma (HNSCC).
      PATIENTS AND METHODS: Sixteen patients with histologically proven HNSCC (11 cases
      primary tumors and in 5 patients with local tumor recurrence) were included in
      the study. DCE imaging was performed in all cases and the following parameters
      were estimated: Ktrans, Ve, Kep, and iAUC. The tumor proliferation index was
      estimated on Ki 67 antigen stained specimens. Microvessel density parameters
      (stained vessel area, total vessel area, number of vessels, and mean vessel
      diameter) were estimated on CD31 antigen stained specimens. Spearman's non
      parametric rank sum correlation coefficients were calculated between DCE and
      different histopathological parameters. RESULTS: The mean values of DCE perfusion
      parameters were as follows: Ktrans 0.189 +/- 0.056 min-1, Kep 0.390 +/- 0.160 min
      1, Ve 0.548 +/- 0.119%, and iAUC 22.40 +/- 12.57. Significant correlations were
      observed between Kep and stained vessel areas (r = 0.51, P = .041) and total
      vessel areas (r = 0.5118, P = .043); between Ve and mean vessel diameter (r = 
      0.59, P = .017). Cell count had a tendency to correlate with Ve (r = -0.48, P =
      .058). In an analysis of the primary HNSCC only, a significant inverse
      correlation between Ktrans and KI 67 was identified (r = -0.62, P = .041). Our
      analysis showed significant correlations between DCE parameters and
      histopathological findings in HNSCC.

PMID- 27888711
TI  - Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages,
      Metastasis, and Histological Grades in Patients with Ovarian Cancer.
AB  - PURPOSE: The monocyte-to-lymphocyte ratio (MLR) has been shown to be associated
      with the prognosis of various solid tumors. This study sought to evaluate the
      important value of the MLR in ovarian cancer patients. METHODS: A total of 133
      ovarian cancer patients and 43 normal controls were retrospectively reviewed. The
      patients' demographics were analyzed along with clinical and pathologic data. The
      counts of peripheral neutrophils, lymphocytes, monocytes, and platelets were
      collected and used to calculate the MLR, neutrophil-to-lymphocyte ratio (NLR).
      and platelet-to-lymphocyte ratio (PLR). The optimal cutoff value of the MLR was
      determined by using receiver operating characteristic curve analysis. We compared
      the MLR, NLR, and PLR between ovarian cancer and normal control patients and
      among patients with different stages and different grades, as well as between
      patients with lymph node metastasis and non-lymph node metastasis. We then
      investigated the value of the MLR in predicting the stage, grade, and lymph node
      positivity by using logistic regression. The impact of the MLR on overall
      survival (OS) was calculated by Kaplan-Meier method and compared by log-rank
      test. RESULTS: Statistically significant differences in the MLR were observed
      between ovarian cancer patients and normal controls. However, no difference was
      found for the NLR and PLR. Highly significant differences in the MLR were found
      among patients with different stages (stage I-II and stage III-IV), grades (G1
      and >G1), and lymph node metastasis status. The MLR was a significant and
      independent risk factor for lymph node metastasis, as determined by logistic
      regression. The optimal cutoff value of the MLR was 0.23. We also classified the
      data according to tumor markers (CA125, CA199, HE4, AFP, and CEA) and
      conventional coagulation parameters (International Normalized Ratio [INR] and
      fibrinogen). Highly significant differences in CA125, CA199, HE4, INR, fibrinogen
      levels, and lactate dehydrogenase were found between the low-MLR group (MLR <=
      0.23) and the high-MLR group (MLR > 0.23). Correspondingly, dramatic differences
      were observed between the two groups in OS. CONCLUSION: Our results show that the
      peripheral blood MLR before surgery could be a significant predictor of advanced
      stages, advanced pathologic grades, and positive lymphatic metastasis in ovarian
      cancer patients.

PMID- 27888710
TI  - PLK1, A Potential Target for Cancer Therapy.
AB  - Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance,
      and completion of mitosis. Dysfunction of PLK1 may promote cancerous
      transformation and drive its progression. PLK1 overexpression has been found in a
      variety of human cancers and was associated with poor prognoses in cancers. Many
      studies have showed that inhibition of PLK1 could lead to death of cancer cells
      by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a
      potential target for cancer therapy. In this article, we examined PLK1's
      structural characteristics, its regulatory roles in cell mitosis, PLK1
      expression, and its association with survival prognoses of cancer patients in a
      wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors
      under investigation. Finally, we discussed the key issues in the development of
      PLK1-targeted cancer therapy.

PMID- 27888712
TI  - Sono-assisted adsorption of a textile dye on milk vetch-derived charcoal
      supported by silica nanopowder.
AB  - This study was performed to assess the efficiency of silica nanopowder (SNP)/milk
      vetch-derived charcoal (MVDC) nanocomposite coupled with the ultrasonic
      irradiation named sono-adsorption process for treating water-contained Basic Red
      46 (BR46) dye. Field emission scanning electron microscopy (FE-SEM), X-ray
      diffraction (XRD), Brunauer-Emmett-Teller (BET) and Fourier transform infrared
      spectroscopy (FT-IR) were performed for the characterization of as-prepared
      adsorbent. The sono-assisted adsorption process was optimized using response
      surface optimization on the basis of central composite design by the application
      of quadratic model. Accordingly, the color removal can be retained more than 93%
      by an initial BR46 concentration of 8 mg/L, sonication time of 31 min, adsorbent
      dosage of 1.2 g/L and initial pH of 9. The pseudo-second order kinetic model
      described the sono-assisted adsorption of BR46 reasonably well (R2 > 0.99). The
      intra-particular diffusion kinetic model pointed out that the sono-assisted
      adsorption of BR46 onto SNP/MVDC nanocomposite was diffusion controlled as well
      as that ultrasonication enhanced the diffusion rate.

PMID- 27888713
TI  - Shattering fruits: variations on a dehiscent theme.
AB  - Fruits are seed dispersal units, and for that they have evolved different
      strategies to facilitate separation and dispersal of the progeny from the mother
      plant. A great proportion of fruits from different clades are dry and dehiscent,
      opening upon maturity to disperse the seeds. In the last two decades, intense
      research mainly in Arabidopsis has uncovered the basic network that controls the
      differentiation of the Arabidopsis fruit dehiscence zone. This review focuses on
      recent discoveries that have helped to complete the picture, as well as the
      insights from evo-devo and crop domestication studies that show how the
      conservation/variation of the elements of this network across species accounts
      for its evolutionary plasticity and the origin of evolutionary innovations.

PMID- 27888714
TI  - A Cryptic Marine Ciliate Feeds on Progametes of Noctiluca scintillans.
AB  - The dinoflagellate Noctiluca scintillans (Noctiluca) has the ability to reproduce
      sexually, which may help to increase or restore its population size during
      periods of blooms or environmental stress. Here, we documented for the first time
      a marine ciliate Strombidium sp. that feeds on Noctiluca's progametes undergoing
      stages 5 to 9 of nuclear division. This ciliate frequently swam on or around
      gametogenic and some vegetative Noctiluca cells. The ciliates associated with
      gametogenic cells had significantly lower swimming speed and changed direction
      more frequently than those associated with vegetative cells, which overall
      increased their time spent around the food patches (progametes). This trophic
      interaction constitutes an upside-down predator-prey link, in which ciliates
      within the typical size range of Noctiluca prey, become the predators. Based on
      the phylogenetic tree (maximum-likelihood), there are 14 environmental clones
      similar to Strombidium sp. found in other coastal waters, where Noctiluca
      presence or blooms have been reported. This novel predator-prey relationship
      could therefore be common in other Noctiluca habitats. Additional studies are
      needed to assess the magnitude of its impacts on Noctiluca population dynamics
      and plankton bloom succession.

PMID- 27888715
TI  - Making a case for controlled organ donation after cardiac death: the story of
      Italy's first experience.
AB  - Donation after circulatory death (DCD) is a valuable option for the procurement
      of organs for transplantation. In Italy, organ procurement after controlled DCD
      is legally and ethically conceivable within the current legislative framework.
      However, although formal impediments do not exist, the health care team is faced
      with many obstacles that may hinder the implementation of such programs. We
      report the case of Italy's first controlled DCD, specifically discussing the role
      of the patient's family in the shared decision-making process. In our case, the
      death of the patient subsequent to the withdrawal of life-sustaining therapies
      was consistent with the patient's wishes, showing respect for his dignity and
      honoring his autonomy, as expressed to his family previously. By making donation
      possible, the medical team was able to fulfill the family's last request on
      behalf of the patient. This case should stimulate deliberation regarding the
      potential to shorten the 20-minute no-touch period currently in place in Italy.
      Such an action would not have injured this patient and would certainly have
      increased the quality of the procured organs.

PMID- 27888716
TI  - Family participation in intensive care unit rounds: Comparing family and provider
      perspectives.
AB  - PURPOSE: To describe and compare intensive care unit (ICU) patient family member
      and provider experiences, preferences, and perceptions of family participation in
      ICU rounds. METHODS: Cross-sectional survey of ICU family members and providers
      of patients admitted to 4 medical-surgical ICUs from September 2014 to March
      2015. MEASUREMENTS AND MAIN RESULTS: Surveys were completed by 63 (62%) family
      members and 258 (43%) providers. Provider respondents included physicians (9%),
      nurses (56%), respiratory therapists (24%), and other ICU team members (11%).
      Although 38% of providers estimated only moderate family member interest in
      participating in rounds, 97% of family members expressed high interest. Family
      members and providers reported listening (95% vs 96%; P=.594) and sharing
      information about the patient (82% vs 82%; P=.995) as appropriate roles for
      family members during rounds, but differed in their perceptions on asking
      questions (75% vs 86%; P=.043) and participating in decision making (36% vs 59%;
      P=.003). Compared with family members, providers were more likely to perceive
      family participation in rounds to cause family stress (7% vs 22%; P=.020) and
      confusion (0% vs 28%; P<.001). CONCLUSION: Family members and providers share
      some perspectives on family participation in ICU rounds although other
      perspectives are discordant, with implications for communication strategies and
      collaborative decision making.

PMID- 27888717
TI  - The role of ficolin-like protein (PcFLP1) in the antibacterial immunity of red
      swamp crayfish (Procambarus clarkii).
AB  - In invertebrates, ficolin-like proteins (FLPs) play important roles in innate
      immunity against pathogens. Previous studies primarily investigated the functions
      of FLPs in immune recognition, activation, and regulation. However, limited
      research has examined the functions of FLPs as immune effectors. In this work, a
      ficolin-like protein was identified in red swam crayfish (Procambarus clarkii)
      and designated as PcFLP1. Quantitative RT-PCR and western blot were employed to
      analyze the distribution and expression profiles of PcFLP1 in the tissues of the
      crayfish. The results indicated that PcFLP1 was present in all tested tissues,
      including hemocytes, heart, hepatopancreas, gill, stomach, and mid-intestine. The
      expression level of PcFLP1 was up-regulated in hemocytes, hepatopancreas and mid
      intestines of the crayfish challenged with Vibrio parahaemolyticus. Further study
      demonstrated that PcFLP1 could protect the hepatopancreatic cells of crayfish
      from V. parahaemolyticus infection. The recombinant PcFLP1 enhanced bacterial
      elimination in crayfish, whereas the antibacterial action was inhibited after
      PcFLP1 was knocked down. Furthermore, PcFLP1 could bound to bacteria and
      inhibited bacterial replication. These results demonstrated that PcFLP1 plays an
      important role in the anti-Vibrio immunity of red swamp crayfish.

PMID- 27888718
TI  - Characterization of peritoneal leukemia-associated macrophages in Notch1-induced
      mouse T cell acute lymphoblastic leukemia.
AB  - Macrophages, which have remarkable plasticity, are indispensable cellular
      components and play essential roles in both innate and adaptive immune responses.
      Peritoneal macrophages show unique gene expression profile and peritoneal cavity
      is also involved in leukemia. However, the characteristics of peritoneal leukemia
      associated macrophages (Per LAMs) have not been established. Here we studied the
      phenotype of Per LAMs, their subpopulations in Notch1-induced acute lymphoblastic
      leukemia mice and compared with LAMs from BM or spleen in the same model.
      Peritoneal macrophages and Per LAMs simultaneously expressed high level iNOS and
      Arg1, which was not commonly observed in macrophages from different origins.
      Furthermore, LAMs from peritoneal, BM and spleen expressed lower level CSF-1, TGF
      beta1 and VEGF-A than tumor-associated macrophages (TAMs). Moreover, diverse
      responses in the expression of some phenotype-associated genes to leukemia
      microenvironments were detected among those LAMs. In addition, Per LAMs can be
      sub-divided into CD206+ and CD206- sub-populations, which expressed both M1- and
      M2-associated genes. These results revealed the unique phenotype of Per
      macrophages and Per LAMs and contributed to better understanding of macrophage
      plasticity and their pathological roles in leukemia.

PMID- 27888719
TI  - Treponema pallidum flagellin FlaA2 induces IL-6 secretion in THP-1 cells via the
      Toll-like receptor 2 signaling pathway.
AB  - Treponema pallidum subsp. pallidum membrane proteins are considered as potent
      inducers in the initiation and development of inflammation. In the present study,
      the mechanism that leads to the production of interleukin 6 (IL-6), one of the
      key proinflammatory cytokines, by human monocytic THP-1 cells when these cells
      are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with
      flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the
      phosphorylation of ERK, p38, and NF-kappaB, but has no effect on the
      phosphorylation of JNK. Likewise, FlaA2-induced IL-6 production was found to be
      attenuated by inhibitors for ERK, p38, and NF-kappaB, but not by JNK inhibitor.
      Immunofluorescence analysis showed that flagellin FlaA2 could stimulate the
      translocation of IkappaBalpha from the cytosol to the nucleus, and this
      phenomenon could be inhibited by the specific inhibitor BAY11-7082. FlaA2-induced
      IL-6 expression was also proved to be abrogated by transfection with dominant
      negative (DN) plasmid of MyD88. We further demonstrated that transfection with DN
      TLR2 was sufficient to attenuate IL-6 expression and the phosphorylation of ERK,
      p38, and IkappaBalpha. These results suggest that flagellin FlaA2 induces IL-6
      production via signaling pathways involving TLR2, MyD88, ERK, p38, and NF-kappaB
      in monocytes, which could contribute to the pathogenesis of T. pallidum.

PMID- 27888720
TI  - Postmortem serum levels of IgE and mast cell tryptase in fatal asthma.
AB  - The aim of this study was to characterize the concentrations of total and
      specific IgE as well as mast cell-derived tryptase in postmortem serum from
      femoral blood and evaluate the usefulness of their determination for diagnostic
      purposes in cases of fatal asthma attacks. 36 autopsy cases were retrospectively
      selected including cases of witnessed death in asthmatic subjects, deaths in
      asthmatics and atopic subjects with causes of death unrelated to asthma or
      allergic anaphylaxis as well as deaths in non-atopic, non-allergic individuals
      with causes of death unrelated to asthma or allergic anaphylaxis. Initial results
      indicated increased postmortem serum total IgE in atopic and asthmatic
      individuals, irrespective of the cause of death. Conversely, increased mast cell
      tryptase levels were noted exclusively in fatal asthma attacks. This suggests
      that mast cell tryptase measurement in cases of death potentially caused by
      severe acute bronchial asthma may be useful for diagnostic purposes.

PMID- 27888721
TI  - Discovery of resveratrol derivatives as novel LSD1 inhibitors: Design, synthesis
      and their biological evaluation.
AB  - Inhibition of lysine-specific demethylase 1 (LSD1) has recently emerged as an
      attractive therapeutic target for treating cancer and other diseases. As a
      continuity of our ongoing effort to identify novel small-molecule LSD1
      inhibitors, we designed and synthesized a series of resveratrol derivatives,
      which were shown to be potent inhibitors of LSD1. Among them, compounds 4e and 4m
      displayed the most potent LSD1-inhibitory activities in enzyme assays, with IC50
      values of 121 nM and 123 nM, respectively. Biochemistry study and docking
      analysis indicated that compounds 4e and 4m were reversible LSD1 inhibitors. High
      content analysis showed that 4e and 4m induced a dose-dependent increase of
      dimethylated Lys4 of histone H3 and had no impact on the expression of LSD1 in
      MGC-803 cells. Furthermore, 4e or 4m could remarkably increase the mRNA level of
      CD86, a surrogate cellular biomarker for LSD1 activity, in MGC-803 cells,
      suggesting that they are likely to exhibit LSD1-inhibitory activities
      intracellularly. These findings should encourage further modification of these
      compounds to produce more potent LSD1 inhibitors with potential anticancer
      activity.

PMID- 27888723
TI  - Deconstructing Bipolar Disorder and Schizophrenia: A cross-diagnostic cluster
      analysis of cognitive phenotypes.
AB  - BACKGROUND: Bipolar disorder (BD) and schizophrenia (SZ) show substantial
      overlap. It has been suggested that a subgroup of patients might contribute to
      these overlapping features. This study employed a cross-diagnostic cluster
      analysis to identify subgroups of individuals with shared cognitive phenotypes.
      METHOD: 143 participants (68 BD patients, 39 SZ patients and 36 healthy controls)
      completed a battery of EEG and performance assessments on perception, nonsocial
      cognition and social cognition. A K-means cluster analysis was conducted with all
      participants across diagnostic groups. Clinical symptoms, functional capacity,
      and functional outcome were assessed in patients. RESULTS: A two-cluster solution
      across 3 groups was the most stable. One cluster including 44 BD patients, 31
      controls and 5 SZ patients showed better cognition (High cluster) than the other
      cluster with 24 BD patients, 35 SZ patients and 5 controls (Low cluster). BD
      patients in the High cluster performed better than BD patients in the Low cluster
      across cognitive domains. Within each cluster, participants with different
      clinical diagnoses showed different profiles across cognitive domains.
      LIMITATIONS: All patients are in the chronic phase and out of mood episode at the
      time of assessment and most of the assessment were behavioral measures.
      CONCLUSIONS: This study identified two clusters with shared cognitive phenotype
      profiles that were not proxies for clinical diagnoses. The finding of better
      social cognitive performance of BD patients than SZ patients in the Lowe cluster
      suggest that relatively preserved social cognition may be important to identify
      disease process distinct to each disorder.

PMID- 27888722
TI  - A pilot study on predictors of brainstem raphe abnormality in patients with major
      depressive disorder.
AB  - BACKGROUND: Hypo/anechogenicity of the brainstem raphe (BR) structures has been
      suggested as a possible transcranial parenchymal sonography (TCS) marker
      associated with depression. AIM: The aim of this study was to analyze possible
      association of the abnormal BR echogenicity in patients with major depression
      when compared to healthy controls, and to evaluate its clinical and genetic
      correlates. METHODS: TCS was performed in 53 patients diagnosed as major
      depressive disorder (MDD) without psychotic symptoms and in 54 healthy matched
      controls. RESULTS: The TCS detected BR abnormalities were significantly more
      frequent in MDD patients (35 out of 53; 66%) in comparison to matched controls (5
      out of 56; 9%). The prevalence of short allele (s) homozygocity in the length
      polymorphism of the promoter region of the serotonin transporter gene (5-HTTLPR)
      was significantly higher in MDD patients relative to those with normal BR
      echogenicity. A stepwise statistical discriminant analysis revealed statistically
      significant separation between MDD patients with and without BR abnormalities
      groups based on the four predictors combined: the Hamilton Anxiety Rating Scale
      item 5 ("difficulty in concentration, poor memory"), presence of social phobia, s
      allele homozygocity of the 5-HTTLPR polymorphism, and presence of generalized
      anxiety disorder. LIMITATIONS: Cross-sectional design and heterogenous treatment
      of depressed patients. CONCLUSIONS: Reduced BR echogenicity in at least a
      subgroup of MDD patients may reflect a particular phenotype, characterized by
      more prevalent comorbid anxiety disorders, associated with particular genetic
      polymorphisms and neurotransmitter(s) deficits, most probably altered
      serotonergic mechanisms.

PMID- 27888724
TI  - The role of physical and mental health multimorbidity in suicidal ideation.
AB  - BACKGROUND: Previous research has focused on the separate roles of mental illness
      and physical health conditions in suicide risk, with relatively few studies
      investigating the importance of physical and psychiatric disorder co-occurrence.
      We aimed to investigate whether suicidal ideation might be influenced by physical
      and mental ill-health multimorbidity. METHODS: Data from the Adult Psychiatric
      Morbidity Survey of England were analysed. Participants who responded to the
      suicidal thoughts question were grouped into four distinct categories based on
      their health conditions (Common mental disorders (CMD) only, physical health
      conditions only, CMD/physical health multimorbidity and a control group with
      neither physical nor mental health conditions). Multinomial logistic regression
      analyses were conducted and odds ratios (OR) and 95% CIs are presented. RESULTS:
      In the fully adjusted model, both the multimorbidity and CMD-only groups were
      associated with higher levels of suicidal ideation relative to the control group.
      LIMITATIONS: Secondary analyses of cross-sectional data. CONCLUSIONS: Although
      multimorbidity was associated with suicidal thoughts, it does not appear to
      elevate risk beyond the independent effects of common mental disorders or
      physical health problems. Primary care and mental health clinicians should
      consider assessment of suicidal ideation among patients with multimorbid
      physical/mental health conditions.

PMID- 27888725
TI  - Functional response of osteoblasts in functionally gradient titanium alloy mesh
      arrays processed by 3D additive manufacturing.
AB  - We elucidate here the osteoblasts functions and cellular activity in 3D printed
      interconnected porous architecture of functionally gradient Ti-6Al-4V alloy mesh
      structures in terms of cell proliferation and growth, distribution of cell
      nuclei, synthesis of proteins (actin, vinculin, and fibronectin), and calcium
      deposition. Cell culture studies with pre-osteoblasts indicated that the
      interconnected porous architecture of functionally gradient mesh arrays was
      conducive to osteoblast functions. However, there were statistically significant
      differences in the cellular response depending on the pore size in the
      functionally gradient structure. The interconnected porous architecture
      contributed to the distribution of cells from the large pore size (G1) to the
      small pore size (G3), with consequent synthesis of extracellular matrix and
      calcium precipitation. The gradient mesh structure significantly impacted cell
      adhesion and influenced the proliferation stage, such that there was high
      distribution of cells on struts of the gradient mesh structure. Actin and
      vinculin showed a significant difference in normalized expression level of
      protein per cell, which was absent in the case of fibronectin. Osteoblasts
      present on mesh struts formed a confluent sheet, bridging the pores through
      numerous cytoplasmic extensions. The gradient mesh structure fabricated by
      electron beam melting was explored to obtain fundamental insights on cellular
      activity with respect to osteoblast functions.

PMID- 27888726
TI  - Probabilistic uncertainty analysis based on Monte Carlo simulations of co
      combustion of hazelnut hull and coal blends: Data-driven modeling and response
      surface optimization.
AB  - The aim of present study is to investigate the thermogravimetric behaviour of the
      co-combustion of hazelnut hull (HH) and coal blends using three approaches: multi
      non-linear regression (MNLR) modeling based on Box-Behnken design (BBD) (1),
      optimization based on response surface methodology (RSM) (2), and probabilistic
      uncertainty analysis based on Monte Carlo simulation as a function of blend
      ratio, heating rate, and temperature (3). The response variable was predicted by
      the best-fit MNLR model with a predicted regression coefficient (R2pred) of
      99.5%. Blend ratio of 90/10 (HH to coal, %wt), temperature of 405 degrees C, and
      heating rate of 44 degrees Cmin-1 were determined as RSM-optimized conditions
      with a mass loss of 87.4%. The validation experiments with three replications
      were performed for justifying the predicted-mass loss percentage and 87.5%+/-0.2
      of mass loss were obtained under RSM-optimized conditions. The probabilistic
      uncertainty analysis were performed by using Monte Carlo simulations.

PMID- 27888727
TI  - Studies of cadmium(II), lead(II), nickel(II), cobalt(II) and chromium(VI)
      sorption on extracellular polymeric substances produced by Rhodococcus opacus and
      Rhodococcus rhodochrous.
AB  - The adsorption of Cd(II), Pb(II), Ni(II), Co(II) and Cr(VI) ions on the
      extracellular polymeric substances (EPS) obtained from bacterial strain
      Rhodococcus opacus and Rhodococcus rhodochrous was investigated by the static
      sorption method. Influence of pH, time and temperature were studied. It was found
      that the influence of the pH value and time of adsorption depends on the type of
      adsorbed ions. For all investigated systems an increase of temperature above 35
      degrees C reduces adsorption. However, the static sorption capacities values
      oscillate around 1.5mmol/g, independently of the type of the studied metal ions.
      The adsorption mechanism of studied metal ions onto the tested EPSs seems to be
      very complex and it is probably due to an electrostatic attraction, a surface
      complex formation and chemical interaction between the metal ions and the
      functional groups (mainly hydroxyl, acetamido or amino groups) of bacterial
      extracellular biopolymers.

PMID- 27888728
TI  - Estimating total lipid content of Camelina sativa via pyrolysis assisted in-situ
      transesterification with dimethyl carbonate.
AB  - Direct derivatization of C. sativa seed into FAMEs without lipid extraction was
      conducted for the quantification of lipid analysis via in-situ thermal
      methylation with dimethyl carbonate as an acyl acceptor on silica (SiO2). The
      introduced method had an extraordinarily high tolerance against impurities such
      as pyrolytic products and moisture. To ensure the technical completeness of in
      situ methylation, thermal cracking of FAMEs transformed from C. sativa seed was
      also explored. Thermal cracking of unsaturated FAMEs such as C18:1, C18:2, C18:3
      and C20:1 occurred at temperatures higher than 365 degrees C due to their thermal
      instability. Thus, experimental findings in this study suggests not only that
      qualitative analysis of fatty acid profile in C. sativa seed via in-situ
      methylation using SiO2 could be achieve, but also that the total lipid content
      (42.65wt.%) in C. sativa seed could be accurately estimated.

PMID- 27888729
TI  - Fractionation of rapeseed straw by hydrothermal/dilute acid pretreatment combined
      with alkali post-treatment for improving its enzymatic hydrolysis.
AB  - The aim of the research was to evaluate the effect of combined treatments on
      fermentable sugar production from rapeseed straw. An optimum condition was found
      to be the combination of hydrothermal pretreatment at 180 degrees C for 45min and
      post-treatment by 2% NaOH at 100 degrees C for 2h, which was based on the
      quantity of monosaccharides released during enzymatic hydrolysis. As compared
      with the raw material without treatment, the combination of hydrothermal
      pretreatment and alkali post-treatment resulted in a significant increase of the
      saccharification rate by 5.9times. This process potentially turned rapeseed straw
      into value added products in accordance with the biorefinery concept.

PMID- 27888730
TI  - Production and purification of amylolytic enzymes for saccharification of
      microalgal biomass.
AB  - The aim of this study was the production of amylolytic enzymes by solid state or
      submerged fermentations (SSF or SF, respectively), followed by purification using
      chemical process or microfiltration and immobilization of purified enzymes in a
      polyurethane support. The free and immobilized enzymes obtained were used to
      evaluate enzymatic hydrolysis of the polysaccharides of Spirulina.
      Microfiltration of the crude extracts resulted in an increase in their specific
      activity and thermal stability at 40 degrees C and 50 degrees C for 24h, as
      compared to extracts obtained by SSF and SF. Immobilization of polyurethane
      purified enzyme produced yields of 332% and 205% for the enzymes obtained by SF
      and SSF, respectively. Free or immobilized enzymes favor the generation of
      fermentable sugar, being the application of the purified and immobilized enzymes
      in the hydrolysis of microalgal polysaccharides considered a promising
      alternative towards development of the bioethanol production process from
      microalgal biomass.

PMID- 27888731
TI  - Kelp waste extracts combined with acetate enhances the biofuel characteristics of
      Chlorella sorokiniana.
AB  - To probe the effect of kelp waste extracts (KWE) combined with acetate on
      biochemical composition of Chlorella sorokiniana, the cultures were performed
      under independent/combined treatment of KWE and acetate. The results showed that
      high cell density and biomass were obtained by KWE combined with acetate
      treatments, whose biomass productivity increased by 79.69-102.57% and 20.04
      35.32% compared with 3.0gL-1 acetate and KWE treatments respectively. The maximal
      neutral lipid per cell and lipid productivity were gained in KWE combined with
      3.0gL-1 acetate treatment, which increased by 16.32% and 129.03% compared with
      3.0gL-1 acetate, and 253.35% and 70.74% compared with KWE treatment. Meanwhile,
      C18:3n3 and C18:2n6c contents were reduced to 4.90% and 11.88%, whereas C16:0 and
      C18:1n9c were improved to 28.71% and 37.76%. Hence, supplementing appropriate
      acetate in KWE cultures is supposed to be a great potential method for large
      scale cultivation of C. sorokiniana to generate biofuel.

PMID- 27888732
TI  - Biorefinery of microalgal soluble proteins by sequential processing and membrane
      filtration.
AB  - A mild biorefinery process was investigated on the microalga Nannochloropsis
      gaditana, to obtain an enriched fraction of water soluble proteins free from
      chlorophyll. After harvesting, a 100g.L-1 solution of cells was first subjected
      to cell disruption by either high-pressure homogenization (HPH) or enzymatic
      treatment (ENZ). HPH resulted in a larger release of proteins (49%) in the
      aqueous phase compared to the Alcalase incubation (35%). In both cases, an
      ultrafiltration/diafiltration (UF/DF) was then performed on the supernatant
      obtained from cell disruption by testing different membrane cut-off (1000kDa,
      500kDa and 300kDa). After optimising the process conditions, the combination of
      ENZ->UF/DF ended in a larger overall yield of water soluble proteins (24.8%) in
      the permeate compared to the combination of HPH->UF/DF (17.4%). A gel
      polarization model was implemented to assess the maximum achievable concentration
      factor during ultrafiltration and the mass transfer coefficient related to the
      theoretical permeation flux rate.

PMID- 27888733
TI  - Enhancement of l-lactic acid production via synergism in open co-fermentation of
      Sophora flavescens residues and food waste.
AB  - In this study, Sophora flavescens residues (SFR) were used for l-lactic acid
      production and were mixed with food waste (FW) to assess the effects of different
      compositions of SFR and FW. Positive synergistic effects of mixed substrates were
      achieved with co-fermentation. Co-fermentation increased the proportion of l
      lactic acid by decreasing the co-products of ethanol and other organic acids. A
      maximum l-lactic acid concentration of 48.4g/L and l-lactic acid conversion rate
      of 0.904g/g total sugar were obtained through co-fermentation of SFR and FW at
      the optimal ratio of 1:1.5. These results were approximately 6-fold those
      obtained during mono-fermentation of SFR. Co-fermentation of SFR and FW provides
      a suitable C/N ratio and pH for effective open fermentative production of l
      lactic acid.

PMID- 27888734
TI  - Production and characterization of rhamnolipid using palm oil agricultural
      refinery waste.
AB  - In this research we assess the feasibility of using palm oil agricultural
      refinery waste as a carbon source for the production of rhamnolipid biosurfactant
      through fermentation. The production and characterization of rhamnolipid produced
      by Pseudomonas aeruginosa PAO1 grown on palm fatty acid distillate (PFAD) under
      batch fermentation were investigated. Results show that P. aeruginosa PAO1 can
      grow and produce 0.43gL-1 of rhamnolipid using PFAD as the sole carbon source.
      Identification of the biosurfactant product using mass spectrometry confirmed the
      presence of monorhamnolipid and dirhamnolipid. The rhamnolipid produced from PFAD
      were able to reduce surface tension to 29mNm-1 with a critical micelle
      concentration (CMC) 420mgL-1 and emulsify kerosene and sunflower oil, with an
      emulsion index up to 30%. Results demonstrate that PFAD could be used as a low
      cost substrate for rhamnolipid production, utilizing and transforming it into a
      value added biosurfactant product.

PMID- 27888735
TI  - Leisure participation and subjective well-being: Exploring gender differences
      among elderly in Shanghai, China.
AB  - OBJECTIVES: To explore the association between leisure participation and
      subjective well-being and the role gender in this issue among elderly Chinese in
      Shanghai, China. METHODS: Principal components analysis and logistic regressions
      are used to analyze the cross-sectional data of the 2013 Shanghai Elderly Life
      and Opinion Survey that contains 2884 respondents (60+ with a mean age of 72.6)
      recruited from a multistage cluster sampling design. Subjective well-being is
      measured by happiness and life satisfaction, and leisure participation is
      examined by the type and diversity of leisure activities. RESULTS: Principal
      components analysis identifies four major types of leisure activity that elderly
      Chinese are actively engaged in-detachment-recovery, aesthetic, social, and
      performing-arts activities. Among them, social activities and performing-arts
      activities have the most relevance to subjective well-being. Females are more
      likely to engage in social and performing-arts activities whereas males are more
      likely to engage in detachment-recovery and aesthetic activities. Performing-arts
      activities promote subjective well-being only for females. Social activities are
      beneficial for both gender groups, but more so for males than for females. While
      increased levels of leisure diversity are linearly related to increased odds of
      subjective well-being for females, moderate level of leisure diversity is found
      to be the most important for males. CONCLUSIONS: Leisure participation is
      positively related to subjective well-being among elderly Chinese, and thus could
      play a critical role in promoting healthy aging. The major gender differences as
      observed suggest the need to further explore gender-specific barriers in leisure
      participation.

PMID- 27888736
TI  - Activity engagement and physical function in old age sample.
AB  - OBJECTIVES: To describe the patterns of engagement in mental, physical, and
      social activity (MA, PA, and SA) and to examine the relationship between combined
      activity engagement and physical function among community-dwelling older adults.
      DESIGN: Cross-sectional correlational study. SETTING: Multiple communities.
      PARTICIPANTS: A total of 466 individuals aged 55 years or older. MEASUREMENTS:
      Physical function was assessed using grip strength and gait speed. Engagement in
      PA, MA and SA was obtained from self-report questionnaires. RESULTS: We
      identified four classes ("Active PA and MA", "Active MA", "Active PA", and
      "Inactive") that significantly differed in the frequency of engagement in MA and
      PA using latent class analysis. SA didn't differ across classes. Controlling for
      age, the "Active PA and MA", "Active MA", "Active PA" groups displayed similar
      grip strength that was superior to the "Inactive" group. "Active PA and MA" group
      had best gait speed relative to other groups, especially "Active MA" and
      "Inactive" group, while the "Active PA", "Active MA", and "Inactive" group were
      similar in gait speed. CONCLUSION: Combined physical and mental activity
      engagement was associated with better physical function, especially in gait
      speed. Future interventional research should investigate the combination of both
      physical and cognitive training to prevent decline of physical function in older
      adults.

PMID- 27888737
TI  - An intervention to improve sibling relationship quality among youth in foster
      care: Results of a randomized clinical trial.
AB  - Sibling programming is an important part of a prevention framework, particularly
      for youth in foster care. After children are removed from their families and
      placed into foster care in the aftermath of maltreatment, the sibling
      relationship is often the most viable ongoing relationship available to the
      child, and may be critical to a youth's sense of connection, emotional support,
      and continuity. The promise of dyadic sibling programming in particular rests on
      the ability of interventions to enhance the quality of sibling relationships; yet
      little research exists that suggests that sibling interventions can improve
      relationship quality among foster youth. The primary aim of the current study was
      to examine the effects of a specific dyadic sibling-focused intervention for
      older and younger siblings on sibling relationship quality. One hundred sixty
      four dyads (328 youth) participated in the study, with each dyad consisting of an
      older sibling between 11 and 15 years of age at baseline and a younger sibling
      separated in age by less than 4 years. Hierarchical linear models were applied to
      self-reported, observer-reported and observational data over the 18-month study
      period. Findings suggest that the sibling intervention holds promise for
      improving sibling relationship quality among youth in foster care. Implications
      and future directions for research are discussed.

PMID- 27888739
TI  - Microwave-assisted one pot synthesis, characterization, biological evaluation and
      molecular docking studies of steroidal thiazoles.
AB  - In the present manuscript, a series of steroidal thiazole derivatives (4-6, 8)
      have been synthesized in efficient manner by one step reaction methodology
      employing microwave irradiation. The synthesis involves the reaction of steroidal
      ketones (1-3, 7) with thiosemicarbazide and phenacyl bromide. Structural
      assignment of the products was confirmed on the basis of IR, 1H NMR, 13C NMR, MS
      and analytical data. The synthesized compounds were screened for in vitro
      antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. In
      addition, the products 4-6, 8 were also tested for pBR322 DNA cleavage activity,
      genotoxicity, reactive oxygen species (ROS) production and RBC hemolysis.
      Molecular docking analysis was carried out to validate the specific binding mode
      of the newly synthesized compounds into the active site of DNA. Docking showed
      formation of more stable complexes of compounds 4 and 8 with the free binding
      energies -8.1 and -8kcal/mol, respectively. Hence, it could be suggested that the
      steroidal compounds bearing a core thiazole scaffold would be a potent biological
      agent.

PMID- 27888738
TI  - Oxyntomodulin analog and exendin-4 derivative lower plasma glucose in cattle.
AB  - The present study was undertaken with the aim of examining whether and how
      exendin-4 (1-3) fragment, ie, Ex-4 (1-3) fragment, contributes to the regulation
      of glucose. An analog of oxyntomodulin (OXM) ([Gly2, Glu3]-OXM), a glucagon
      analog ([Gly2, Glu3]-glucagon), and two derivatives of Ex-4 (glucandin and [Gly2,
      Glu3]-glucandin) were synthesized by substituting with Gly2, Glu3 at the N
      terminuses of OXM and glucagon and/or by attaching Ex-4 (30-39) amide at the C
      terminus of glucagon. Effects of these peptides on plasma insulin and glucose
      concentrations were investigated in cattle by conducting 3 in vivo experiments.
      In all 3 experiments, 0.1% BSA saline was injected as a control. In experiment 1,
      glucandin (amino acid sequence was glucagon [1-29]-Ex-4 [30-39] amide) and [Gly2,
      Glu3]-glucandin were injected at the dose rates of 5 MUg/kg BW in 4-mo-old
      Holstein steers. Results showed that glucoregulatory effects of glucandin were
      similar to those of glucagon. [Gly2, Glu3]-glucandin stimulated insulin secretion
      at 2 to 10 min and lowered glucose concentrations at 15 to 75 min. Experiment 2
      was carried out to better understand the glucose-lowering potency of [Gly2, Glu3]
      glucandin, in comparison with Ex-4 and glucagon-like peptide-1 (GLP-1), using 4.5
      mo-old Holstein steers. [Gly2, Glu3]-glucandin was injected at dose rates of 0.3
      MUg/kg BW, 1.0 MUg/kg BW, 3.2 MUg/kg BW, and 6.4 MUg/kg BW. Ex-4 and GLP-1 were
      injected at dose rates of 0.3 MUg/kg BW. Results showed that the insulinotropic
      and glucose-lowering effects of [Gly2, Glu3]-glucandin were not as potent as for
      Ex-4 and GLP-1, and the minimum effective dose of [Gly2, Glu3]-glucandin to
      regulate plasma glucose concentrations was 3.2 MUg/kg BW. In experiment 3, [Gly2,
      Glu3]-OXM and [Gly2, Glu3]-glucagon were injected at dose rates of 5 MUg/kg BW in
      5-mo-old Holstein steers. Both [Gly2, Glu3]-OXM and [Gly2, Glu3]-glucagon
      increased insulin concentration. [Gly2, Glu3]-OXM potently lowered plasma
      glucose, but [Gly2, Glu3]-glucagon did not change it. In summary, our findings
      clearly demonstrate that Ex-4 (1-3) fragment contributes to the regulation of
      glucose. [Gly2, Glu3]-OXM and [Gly2, Glu3]-glucandin are insulinotropic and
      glucose-lowering peptides. It was of interest that the substitution of the first
      3 amino acids of OXM with Ex-4 (1-3) could reverse the upregulation of glucose by
      OXM into downregulation of glucose. In lowering glycemia, [Gly2, Glu3]-OXM seemed
      almost as effective as Ex-4, and [Gly2, Glu3]-glucandin was less profound than Ex
      4. These findings contributed new insights into the hormonal regulation of
      glucose in ruminants. The action of [Gly2, Glu3]-OXM and [Gly2, Glu3]-glucandin
      might provide an advantage in glycemic control of insulin resistance in cattle
      and humans.

PMID- 27888740
TI  - Measuring ultra-weak photon emission as a non-invasive diagnostic tool for
      detecting early-stage type 2 diabetes: A step toward personalized medicine.
AB  - The global prevalence of type 2 diabetes is estimated to reach 4.4% by 2030,
      placing a significant burden on our healthcare system. Therefore, the ability to
      identify patients in early stages of the disease is essential for both prevention
      and effective management, and diagnostic methods based on traditional Chinese
      medicine (TCM) may be suitable for identifying patients with early-stage type 2
      diabetes. Here, a panel of three physicians trained in TCM classified 44 pre
      diabetic subjects into three syndrome subtypes using TCM-based diagnostics. In
      addition, ultra-weak photon emission (UPE) was measured at four anatomical sites
      in each subject. Ten properties encompassing 40 parameters were then extracted
      from the UPE time series. Statistical analyses, including multinomial logistic
      regression, were performed using the results of each parameter measured at the
      four sites. Sixteen UPE parameters were then selected and used to discriminate
      between the three subtypes of pre-diabetic subjects. Next, Spearman's correlation
      coefficient was used to quantify the correlation between the 16 UPE parameters
      and the TCM-based diagnoses. The resulting correlation networks accurately
      reflected the differences between the three syndrome subtypes. These results
      suggest that UPE is a suitable tool for detecting subtypes in early-stage type 2
      diabetes. In addition, our results provide evidence that TCM may represent an
      important step toward personalized medicine.

PMID- 27888741
TI  - Cell-type dependent response to photodynamic treatment in 3D collagen cell
      cultures.
AB  - Photodynamic therapy (PDT) can induce direct tumor cell destruction, indirect
      tumor cell inactivation due to vascular occlusion as well as immune response.
      Evidence suggests that the PDT-induced cell death is dependent on both PDT
      protocol-related as well as microenvironmental factors, and its mode is also
      decisive for the type of immune response. This suggests potential
      interrelationship among PDT-induced tumor cell destruction, immune response and
      microenvironmental factors. In the present study we analyzed the effect of a
      microenvironmental factor - extracellular matrix on the cellular response to
      photodynamic treatment in vitro. By using conventional proliferation and modified
      cell survival assays as well as fluorescence imaging, we compared efficacy of
      aminolevulinic acid (ALA)-PDT to inactivate three esophageal cell lines in two-
      and three-dimensional formats. Modified cell colony assay indicated comparable
      PDT doses leading to death of both Kyse 450 and Het-1A cells on plastic, whereas
      Kyse 70 cells were only partially responsive. In 3D collagen matrices, we were
      able to induce only death of Kyse 450 cells by ALA-PDT, if analyzed 24h after
      treatment. Consistently, only Kyse 450 cells were able to produce detectable
      amounts of PpIX after incubation of their 3D collagen cultures with ALA. Our
      results demonstrate that cellular response to ALA-PDT is cell-type dependent both
      in two- and three-dimensional formats and indicate that the extracellular matrix
      might modify it.

PMID- 27888742
TI  - Serological evidence for high prevalence of Influenza D Viruses in Cattle,
      Nebraska, United States, 2003-2004.
AB  - Influenza D virus (IDV), a new member of the influenza virus family, was first
      reported in 2011 in swine in Oklahoma, USA, and then soon found in cattle across
      North America and Eurasia. Earlier studies suggested cattle serve as natural
      reservoir for IDV. The goal of this study is to perform a retrospective study
      looking at sera collected from Nebraska beef herds in 2003-2004 and 2014 for
      evidence of IDV antibodies. Results showed that all 40 randomly selected farms
      (2003-2004) we tested contained IDV seropositive adult animals and that
      approximately 98% of newborn calves (2014) had high levels of maternal antibodies
      against IDV. This study suggested that IDV exposures were present in Nebraska
      beef cattle since at least 2003.

PMID- 27888743
TI  - Plasmapheresis for refractory status epilepticus Part II: A scoping systematic
      review of the pediatric literature.
AB  - BACKGROUND: Our goal was to perform a scoping systematic review of the literature
      on the use of plasmapheresis or plasma exchange (PE) for refractory status
      epilepticus (RSE) in children. METHODS: Articles from MEDLINE, BIOSIS, EMBASE,
      Global Health, Healthstar, Scopus, Cochrane Library, the International Clinical
      Trials Registry Platform, clinicaltrials.gov (inception to May 2016), reference
      lists of relevant articles, and gray literature were searched. The strength of
      evidence was adjudicated using both the Oxford and GRADE methodology by two
      independent reviewers. RESULTS: Twenty-two original articles were identified,
      with 37 pediatric patients. The mean age of the patients was 8.3 years (age
      median: 8.5, range: 0.6 years-17 years). Seizure response to PE therapy occurred
      in 9 of the 37 patients (24.3%) included in the review, with 7 patients (18.9%)
      displaying resolution of seizures and 2 patients (5.4%) displaying a partial
      reduction in seizure volume. Twenty-eight of the 37 patients (75.7%) had no
      response to PE therapy. No adverse events were recorded. CONCLUSIONS: Oxford
      level 4, GRADE D evidence exists to suggest little to no benefit of PE in
      pediatric RSE. Routine application of PE for pediatric RSE cannot be recommended
      at this time.

PMID- 27888744
TI  - Bilateral changes in muscle architecture of physically active people with chronic
      stroke: A quantitative muscle ultrasound study.
AB  - OBJECTIVE: Changes in muscle architecture after stroke are usually assessed by
      investigating inter-limb differences. As a result bilateral changes of muscle
      architecture might be missed. Our aim was to investigate whether bilateral
      architectural changes in skeletal muscle can be detected in chronic, physically
      active stroke patients using quantitative muscle ultrasound (QMUS). METHODS:
      Twenty-eight patients (mean time since stroke 5.2years, median Brunnstrom stage
      4) were recruited. QMUS images were obtained bilaterally from 2 arm and 4 leg
      muscles. Corrected echogenicity (muscle ultrasound grayvalue) and muscle
      thickness were compared to reference values obtained from healthy subjects.
      Correlations of muscle changes with demographic, clinical and neurophysiological
      characteristics were explored. RESULTS: Out of 6 muscles, a significant increase
      in mean echogenicity was found in 4 paretic and 3 non-paretic side muscles.
      Significant decreases in mean muscle thickness were found in 2 paretic side
      muscles and 1 non-paretic side muscle. Echogenicity of the medial gastrocnemius
      correlated moderately with walking speed (inversely) and time since stroke.
      CONCLUSIONS: This study showed that QMUS is a feasible technique to investigate
      architectural changes in skeletal muscles in the chronic phase of stroke and that
      abnormalities can be found in muscles on both the hemiparetic and non-paretic
      side. SIGNIFICANCE: Intriguing data on bilateral changes in muscles of people
      with stroke is presented. Directions for future research are provided.

PMID- 27888745
TI  - Feasibility of eliciting the H reflex in the masseter muscle in patients under
      general anesthesia.
AB  - OBJECTIVE: To explore the feasibility of eliciting the brainstem H reflex in the
      masseter muscle in patients under general anesthesia. METHODS: We electrically
      stimulated the masseteric nerve, a branch of the trigeminal nerve, and recorded
      ipsilateral masseteric and temporalis muscle responses. We tested eight patients
      who presented with trigeminal neuralgia; one patient had a temporal bone tumor
      and one patient had a brainstem arteriovenous malformation. All responses were
      elicited when patients were under general anesthesia and before the initiation of
      surgery. RESULTS: The H reflex in the masseter muscle was reliably elicited in
      70% of the patients. The reflexes met the usual criteria for the H reflex because
      they were elicited below the threshold of the direct M response, and their
      amplitudes decreased when the M response increased with stronger stimuli. The
      mean onset latencies of the masseter H reflex and the M response were 5.4+/-1.3ms
      and 2.6+/-0.6ms, respectively. CONCLUSIONS: In the present study, we provide
      evidence of the feasibility of eliciting the H reflex in the masseter muscles of
      patients under general anesthesia. SIGNIFICANCE: The H reflex of the masseter
      muscle may represent a new method available for intraoperative monitoring.
      Specifically, this method may be important for the monitoring of brainstem
      functional integrity, particularly in the midbrain and mid-pons, in addition to
      the trigeminal nerve path.

PMID- 27888748
TI  - Help me if you can: Evaluating the effectiveness of interpersonal compared to
      intrapersonal emotion regulation in reducing distress.
AB  - BACKGROUND AND OBJECTIVES: Although humans have developed abundant strategies to
      down regulate their own negative emotions, at times of distress they frequently
      turn to significant others to seek comfort. In the present study we use a novel
      performance-based paradigm to evaluate the effectiveness of this interaction.
      METHODS: Forty-seven couples in a long-term relationship volunteered to
      participate in the study. In each couple the two partners were randomly assigned
      as either target or regulator. The target viewed pictures with negative valance.
      In response to each picture he/she was then instructed to choose and apply a
      regulatory strategy (i.e., intrapersonal emotion regulation) or to apply a
      regulatory strategy chosen by his/her partner, the regulator (i.e., interpersonal
      emotion regulation). RESULTS: We found that the outside perspective of the
      regulator helped reducing distress more effectively than intrapersonal emotion
      regulation. Moreover, the cognitive, but not the emotional, empathy of the
      regulator predicted the added value of interpersonal emotion regulation.
      Specifically, regulators with a better ability to understand their partners'
      point of view, selected regulatory strategies that reduced levels of distress
      more effectively. LIMITATIONS: While the present study examined possible effects
      of depression, anxiety and the ability to identify and describe feelings, a
      larger sample is needed in order to optimally address their potential moderating
      effect. CONCLUSIONS: The results illuminate the value of non-professional
      interventions and the importance of cognitive empathy in reducing distress. The
      study has significant clinical implications, providing a simple behavioral tool
      that can be used to decrease and prevent psychopathology.

PMID- 27888746
TI  - Maternal exposure to ozone and PM2.5 and the prevalence of orofacial clefts in
      four U.S. states.
AB  - BACKGROUND: While there is some evidence that maternal exposure to ambient air
      pollution is associated with orofacial clefts in offspring, the epidemiologic
      studies have been largely equivocal. We evaluated whether maternal exposure to
      elevated county-level ambient fine particulate matter with aerodynamic diameter
      <=2.5um (PM2.5) and ozone during early gestation was associated with a higher
      prevalence of orofacial clefts. METHODS: Birth data consisting of 4.7 million
      births from 2001 to 2007 were obtained from National Birth Defects Prevention
      Network for four states - Arizona, Florida, New York (excluding New York City),
      and Texas. The air pollution exposure assessment for gestational weeks 5-10 was
      based on county-level average concentrations of PM2.5 and ozone data generated
      using a Bayesian fusion model available through CDC's Environmental Public Health
      Tracking Network. Two outcomes were analyzed separately: cleft lip with or
      without cleft palate, cleft palate alone. In logistic regression analyses, we
      adjusted for factors that were suspected confounders or modifiers of the
      association between the prevalence of orofacial clefts and air pollution, i.e.,
      infant sex, race-ethnicity, maternal education, smoking status during pregnancy,
      whether this was mother's first baby, maternal age. RESULTS: Each 10ug/m3
      increase in PM2.5 concentration was significantly associated with cleft palate
      alone (OR =1.43, 95% CI: 1.11-1.86). There was no significant association between
      PM2.5 concentration and cleft lip with or without cleft palate. No associations
      were observed between ozone exposure and the two outcomes of orofacial clefts.
      CONCLUSIONS: Our study suggests that PM2.5 significantly increased the risk of
      cleft palate alone, but did not change the incidence of cleft lip with or without
      palate. Ozone levels did not correlate with incidence of orofacial clefts.

PMID- 27888747
TI  - Disconfirming contamination-related threat beliefs by exposure plus safety
      behavior.
AB  - BACKGROUND AND OBJECTIVES: Safety behavior (SB) is detrimental to the beneficial
      effects of exposure, because it prevents patients from obtaining evidence that
      disconfirms their excessive threat beliefs. However, previous studies showed that
      cleaning SB during exposure to a contaminant does not prevent a reduction in
      feelings of contamination, fear of contamination, danger, and disgust (CFDD). We
      aimed to directly examine the effect of SB during exposure to a contaminant on
      threat beliefs associated with CFDD. METHOD: Healthy participants were randomly
      assigned to one of three groups: repeated exposure to a contaminant whilst
      abstaining from SB (exposure plus response prevention; E + RP); with the use of
      disinfectant wipes after each instance of exposure (exposure plus SB; E + SB); or
      no exposure or safety behavior (control condition). Participants identified their
      threat belief associated with the contaminant and rated CFDD and the degree to
      which they believed their threat belief at the pre- and post-test. RESULTS: The E
      + RP and E + SB condition resulted in a larger decrease of CFDD and threat belief
      ratings than the control condition, whereas these reductions did not differ
      between the E + RP and E + SB condition. LIMITATIONS: Results were obtained from
      a nonclinical sample, and with a single session of exposure. CONCLUSION: Cleaning
      SB did not impede the beneficial effects of exposure.

PMID- 27888749
TI  - Young people with higher social anxiety are less likely to adopt the perspective
      of another: Data from the Director task.
AB  - BACKGROUND AND OBJECTIVES: Young people with social anxiety display poor social
      functioning but it is unclear whether this is underscored by difficulties in key
      social cognitive abilities, such as perspective taking. Here, we examined whether
      increased social anxiety is associated with reduced accuracy on a perspective
      taking task and whether this relationship is stronger at particular periods
      within adolescence. METHODS: Fifty-nine adolescents aged 11-19 years completed
      the computerised Director Task (DT) and the Social Anxiety Scale for Adolescence.
      In the DT, participants virtually move objects by following either instructions
      given by the 'Director' (who can see only some objects), or a simple rule to
      ignore certain objects. RESULTS: Participants who scored above the clinical cut
      off for social anxiety (n = 17) were less accurate when they had to take the
      perspective of the Director into account than those scoring below cut-off, yet
      performed similarly on control trials. Preliminary analysis indicated that poorer
      performance was most strongly associated with social anxiety in mid-adolescence
      (14-16.5 years). LIMITATIONS: The DT has been used previously to measure online
      perspective taking but the underlying cognitive mechanisms have not been fully
      elucidated. Extending these findings using additional measures of perspective
      taking would be valuable. CONCLUSIONS: Adolescents with higher social anxiety
      were less accurate at taking the perspective of a computerised character, with
      some suggestion that this relationship is strongest during mid-adolescence. If
      replicated, these findings highlight the importance of addressing specific social
      cognitive abilities in the assessment and treatment of adolescent social anxiety.

PMID- 27888750
TI  - Medium platelet volume as a noninvasive predictor of chronic total occlusion in
      non-infarct artery in patients with non-ST-segment elevation myocardial
      infarction and multivessel coronary artery disease.
AB  - BACKGROUND: Chronic total occlusion (CTO) in a noninfarct-related artery (non
      IRA) is an independent predictor of mortality in non-ST elevation myocardial
      infarction (NSTEMI). Mean platelet volume (MPV) is associated with cardiovascular
      events in NSTEMI. Little is known about the predictors of non-IRA-CTO in patients
      with NSTEMI. The purpose of this study was to evaluate the relationship between
      the presence of non-IRA-CTO with MPV level in patients with NSTEMI and
      multivessel coronary artery disease (MVCAD). METHODS: Data of consecutive
      patients with NSTEMI and MVCAD treated in high-volume PCI center between 2006 and
      2012 and included in the prospective registry were divided according to the
      presence of CTO and analyzed. RESULTS: In the group of 685 patients fulfilling
      the inclusion criteria, 308 (45%) patients had CTO (CTO+), and in 377 (55%)
      patients CTO was not observed (CTO-). The MPV level on admission was
      significantly higher in the CTO+ group than in the CTO- group (P<0.0001). In the
      multivariate analysis of the entire study population, independent predictors of
      occurrence of CTO were medium platelet volume (MPV; per 1fL more; odds ratio [OR]
      1.34; 95% confidence interval [CI] 1.15-1.57; P=0.0002) together with left
      ventricular ejection fraction and prior MI. CONCLUSIONS: MPV at admission is
      independently associated with more frequent occurrence of non-IRA CTO in patients
      with NSTEMI and MVCAD.

PMID- 27888751
TI  - Remote ischemic preconditioning attenuates EGR-1 expression following myocardial
      ischemia reperfusion injury through activation of the JAK-STAT pathway.
AB  - BACKGROUND/OBJECTIVES: Remote ischemic preconditioning (RIPC) protects the
      myocardium from ischemia/reperfusion (I/R) injury however the molecular pathways
      involved in cardioprotection are yet to be fully delineated. Transcription factor
      Early growth response-1 (Egr-1) is a key upstream activator in a variety of
      cardiovascular diseases. In this study, we elucidated the role of RIPC in
      modulating the regulation of Egr-1. METHODS: This study subjected rats to
      transient blockade of the left anterior descending (LAD) coronary artery with or
      without prior RIPC of the hind-limb muscle and thereafter excised the heart 24h
      following surgical intervention. In vitro, rat cardiac myoblast H9c2 cells were
      exposed to ischemic preconditioning by subjecting them to 3cycles of alternating
      nitrogen-flushed hypoxia and normoxia. These preconditioned media were added to
      recipient H9c2 cells which were then subjected to 30min of hypoxia followed by
      30min of normoxia to simulate myocardial I/R injury. Thereafter, the effects of
      RIPC on cell viability, apoptosis and inflammatory markers were assessed.
      RESULTS: We showed reduced infarct size and suppressed Egr-1 in the heart of rats
      when RIPC was administered to the hind leg. In vitro, we showed that RIPC
      improved cell viability, reduced apoptosis and attenuated Egr-1 in recipient
      cells. CONCLUSIONS: Selective inhibition of intracellular signaling pathways
      confirmed that RIPC increased production of intracellular nitric oxide (NO) and
      reactive oxygen species (ROS) via activation of the JAK-STAT pathway which then
      inactivated I/R-induced ERK 1/2 signaling pathways, ultimately leading to the
      suppression of Egr-1.

PMID- 27888752
TI  - Factors influencing brain natriuretic peptide levels in healthy pregnant women.
AB  - BACKGROUND: The normal range of plasma brain natriuretic peptide (BNP) in
      pregnant women is still unclear. Moreover, pregnant women experience dynamic body
      weight changes and suffer from anemia, but effects on maternal BNP have not been
      investigated. This study aimed to reveal the normal plasma BNP range and examine
      the effects of physiological changes on BNP among pregnant women. METHODS AND
      RESULTS: Plasma BNP, hemoglobin, plasma creatinine and BMI were measured in 58
      non-pregnant control women and in 773 normal pregnant women at late pregnancy,
      early postpartum and 1-month postpartum. Mean plasma BNP (in pg/mL) was 11.8 (95%
      confidence interval: 0-27.5) in non-pregnant women, 17.9 (0-44.7, p<0.001) at
      late pregnancy, 42.5 (0-112.6, p<0.001) early postpartum and 16.1 (0-43.9,
      p=0.001) 1-month postpartum. Multiple regression analysis revealed that pre
      delivery BNP levels were negatively correlated with BMI (p<0.001) and hemoglobin
      (p=0.002) and positively correlated with creatinine (p<0.001). Post-delivery BNP
      was positively associated with body weight change during pregnancy (p=0.001) and
      post-delivery creatinine (p=0.010) but negatively associated with body weight
      loss at delivery (p<0.001) and post-delivery hemoglobin (p=0.004). CONCLUSION:
      Even normal pregnancy affects plasma BNP, particularly in the early postpartum
      period, indicative of cardiac stress. Plasma BNP levels are affected by BMI, body
      weight changes, creatinine and hemoglobin levels; therefore, these factors should
      be considered when analysing cardiac function and the physiological implications
      of BNP levels in pregnant women.

PMID- 27888753
TI  - Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of
      warfarin and antihyperlipidemics.
AB  - BACKGROUND: Drug interactions, particularly those involving warfarin, are a major
      clinical and public health problem. Minimizing serious bleeding caused by
      anticoagulants is a recent major focus of the United States (US) Department of
      Health and Human Services. This study quantified the risk of gastrointestinal
      bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of
      warfarin and individual antihyperlipidemics. METHODS: The authors conducted a
      high-dimensional propensity score-adjusted cohort study of new concomitant users
      of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five
      states during 1999-2011. Exposure was defined by concomitant use of warfarin plus
      one of eight antihyperlipidemics. The primary outcome measure was a composite of
      GIB/ICH within the first 30days of concomitant use. As a secondary outcome
      measure, GIB/ICH was examined within the first 180days of concomitant use.
      RESULTS: Among 236,691 persons newly-exposed to warfarin and an
      antihyperlipidemic, the crude incidence of GIB/ICH was 13.2 (95% confidence
      interval 12.7 to 13.8) per 100person-years. Users were predominantly older,
      female, and Caucasian. Adjusted hazard ratios (aHRs) for warfarin and individual
      statins were consistent with no association. Warfarin+gemfibrozil was associated
      with an 80% increased risk of GIB/ICH within the first month of concomitant use
      (aHR=1.8, 1.4 to 2.4). Warfarin+fenofibrate was associated with a similar
      increased risk (aHR=1.8, 1.2 to 2.7), yet with an onset during the second month
      of concomitant use. CONCLUSIONS: Among warfarin-treated persons, the use of
      fibrates-but not statins-increases the risk of hospital presentation for GIB/ICH.

PMID- 27888754
TI  - Body mass index is an independent predictor of major bleeding in non-valvular
      atrial fibrillation patients taking dabigatran.
AB  - BACKGROUND/OBJECTIVES: Adverse bleeding events happened more frequently among
      individuals with, or at risk of, a low body mass index (BMI) than others. Despite
      increasing use of dabigatran in atrial fibrillation (AF) patients, the
      relationship between individual BMI and major bleeding events has not been
      clearly elucidated. METHODS: This study was an observational study of 842
      patients who were enrolled and were followed up for a median of 20months to
      monitor the occurrence of the bleeding complications. The patients were divided
      into three study groups according to the BMI tertile ( tertile 1: ?23.9kg/m2,
      n=273; tertile 2: 23.9<BMI?26.5kg/m2, n=290; and tertile 3: >26.5kg/m2, n=279).
      RESULTS: During follow-up, 28 participants suffered from bleeding events. BMI was
      significant predictor of hospitalization for major bleeding (BMI, hazard ratio
      (HR) 0.830, p=0.002). The incorporation of BMI tertile significantly improved the
      outputs of a model that was based on continuous age and HAS-BLED score without
      age component (p=0.001). CONCLUSIONS: Lower BMI is associated with higher
      incidence of major bleeding in these patients. BMI may improve the prediction of
      an increased individual bleeding risk of a patient with AF who has been treated
      with dabigatran.

PMID- 27888755
TI  - High sensitive cardiac troponin T: Testing the test.
AB  - BACKGROUND: High sensitive cardiac troponin T (hs-TnT) found its way into
      everyday clinical routine to diagnose acute myocardial infarction (AMI). However,
      its levels vary considerably based on the underlying pathophysiology of the
      patients. Hence we sought to test the applicability of the currently only
      available hs-TnT assay (Roche Diagnostics, Switzerland) to diagnose acute
      myocardial infarction. METHODS AND PATIENTS: Retrospectively, we analyzed the hs
      TnT results of 1573 patients admitted to a level A university hospital emergency
      department. Overall 323 patients had an acute cardiac event defined as Non-ST
      Elevated Myocardial Infarction (NSTEMI) and 286 patients had a ST-Elevated
      Myocardial Infarction (STEMI). 964 patients served as controls, consisting of
      patients with other cardiac and non-cardiac morbidity. RESULTS: The sensitivity
      of hs-TnT for detecting an acute cardiac event was more than 92% overall. The
      specificity varied around 35% depending on the respective patient cohort. ROC
      curve analysis of the initial hs-TnT results showed that the AUC in total cardiac
      events (STEMI and NSTEMI) was 0.81. Detailed analysis resulted in an AUC of 0.79
      in NSTEMI and 0.84 in STEMI patients detected via the initial hs-TnT. We further
      tested the ESC algorithm for detecting NSTEMI and obtained a sensitivity of about
      83%, while 43% of all non-NSTEMIs are classified as NSTEMIs. CONCLUSION: We show
      that the specificity of hs-TnT for AMI is very low and conclude that the current
      assay including its delta values represents myocardial damage of any origin. This
      damage alone does not substantiate an AMI diagnosis even when international
      algorithms are applied.

PMID- 27888756
TI  - Isolated heart transplant and combined heart-liver transplant in adult congenital
      heart disease patients: Insights from the united network of organ sharing.
AB  - BACKGROUND/METHODS: The aging patient with severe congenital heart disease (CHD)
      faces many challenges: heart failure, arrhythmia, and in the Fontan patient,
      liver disease. Our goal was to define combined heart liver transplant (CHLT) and
      isolated orthotopic heart transplant (OHT) outcomes in U.S. adult CHD patients.
      The U.S. United Network for Organ Sharing (UNOS) thoracic and liver databases
      were queried for cardiac and CHD diagnoses, from inception-2014. RESULTS: In
      CHLT, CHD made up 22% of waitlist patients (non-CHD n=262 vs. CHD n=58), and 20%
      of transplanted patients (non-CHD n=137 vs. CHD n=27). Liver function tests in
      the non-CHD and CHD groups were similar and there was no difference in CHD and
      non-CHD survival (HR 0.93, CI: 0.36-2.38, p 0.48). In isolated OHT, CHD patients
      comprised 2% of those listed (non-CHD n=74,080 vs. CHD n=1599) and transplanted
      (non-CHD n=48,985 vs. CHD n=967) and had higher early (<1year) mortality (HR
      1.36, CI: 1.18-1.57, p<0.0001), but better long-term survival (HR 0.66, CI; 0.57
      0.76, p<0.001) than non-CHD. Both groups benefitted from mechanical support when
      used (non-CHD HR 0.34, CI: 0.31-0.37 and CHD HR 0.14, CI: 0.03-0.58) and prior
      sternotomy had no effect on mortality in CHD (HR 0.63, CI: 0.15-2.58).
      CONCLUSIONS: Survival of CHD patients undergoing CHLT is no different than in non
      CHD, encouraging consideration of CHLT when clinically appropriate. Short-term
      mortality is higher in CHD (vs. non-CHD) patients undergoing OHT, regardless of
      prior cardiac surgery status. Modifications to CHD classification within UNOS
      would help better understand CHD CHLT and OHT outcomes.

PMID- 27888757
TI  - BMP4/Id2 signaling pathway is a novel therapeutic target for late outgrowth
      endothelial progenitor cell-mediated endothelial injury repair.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) play a pivotal role in
      endothelial repair following artery injury, however, the molecular mechanism of
      late outgrowth EPCs (LEPCs) in endothelial repair remained to be studied. Bone
      morphogenetic protein 4 (BMP4) is involved in vascular injury-mediated
      mobilization and homing of LEPCs. Here, we investigated the influence of BMP4
      modified signaling pathway in LEPC-related endothelial repair of human and
      underlying molecular mechanism. METHODS AND RESULTS: In vitro, after a 28day
      culture, human LEPCs were pretreated with different concentrations of recombinant
      BMP4 (0, 10, 50, or 100ng/mL), which markedly augmented the migration and
      adhesion in vitro and demonstrated a significantly accelerated in vivo
      endothelial repair capacity of human LEPCs after transplantation into nude mice
      with carotid artery denudation injury. Moreover, the main Id gene (Id2), a well
      characterized down-streaming target of BMP4, upregulated in LEPCs incubated with
      recombinant BMP4. The BMP4-induced enhancement in in vitro functional activities
      and in vivo endothelial repair capacity of human LEPCs were abolished by
      pretreatment with BMP antagonist Noggin or shRNA-mediated knockdown of BMP4
      expression. Furthermore, BMP4 gene transfer remarkably activated BMP4-mediated
      signaling pathway and facilitated therapeutic endothelial repair capacity of
      LEPCs, and the improved functional activities of human LEPCs could be inhibited
      by Noggin. CONCLUSION: Thus, the present study demonstrates for the first time
      that BMP4-related signaling pathway is essential with endothelial repair capacity
      of LEPCs in human. The upregulation of BMP4-modified signaling pathway in human
      LEPCs may be a novel therapeutic strategy for endothelial repair after injury.

PMID- 27888758
TI  - Left atrium and pulmonary vein imaging using sub-millisiviert cardiac computed
      tomography: Impact on radiofrequency catheter ablation cumulative radiation
      exposure and outcome in atrial fibrillation patients.
AB  - BACKGROUND: The outcome of radiofrequency catheter ablation (RFCA) of atrial
      fibrillation (AF) has improved thanks to left atrium (LA) anatomy reconstruction
      by cardiac computed tomography (CCT). A new model-based iterative reconstruction
      algorithm (MBIR) provides image noise reduction achieving effective radiation
      dose (ED) close to chest X-ray exposure. Aim of this study was comparing RFCA
      procedural characteristics, AF recurrence and radiation exposure between patients
      in whom RFCA was guided by CCT image integration with MBIR versus a CCT standard
      protocol. METHODS: Three-hundred consecutive patients with drug-refractory AF
      were studied with CCT using MBIR (Group 1; N:150) or CCT with standard protocol
      (Group 2; N:150) for LA evaluation and treated by image integration-supported
      RFCA. Image noise, signal to noise ratio (SNR), contrast to noise ratio (CNR),
      RFCA procedural characteristics, rate of AF recurrence and radiation exposure
      were compared. RESULTS: Group 1 showed higher SNR (25.9+/-7.1 vs. 16.2+/-4.8,
      p<0.001) and CNR (23.3+/-7.1 vs. 12.2+/-4.2, p<0.001) and lower image noise
      (22.3+/-5.2 vs. 32.6+/-8.1 HU, p<0.001), fluoroscopy time (21+/-12 vs. 29+/
      15min, p<0.01) and procedural duration (135+/-89 vs. 172+/-55, p<0.001). Group 1
      showed a 94% reduction of ED as compared to Group 2 (CCT-ED related: 0.41+/-0.04
      vs. 6.17+/-4.11mSv, p<0.001; cumulative CCT+RFCA-ED related: 21.9+/-17.9 vs.
      36.0+/-24.1mSv, p<0.001) with similar rate of AF recurrence (25% vs. 29%,
      p=0.437). CONCLUSIONS: CCT with MBIR allows accurate reconstruction of LA anatomy
      in AF patients undergoing RFCA with a sub-millisievert ED and comparable success
      rate of RFCA as compared to a standard CCT scan protocol.

PMID- 27888759
TI  - Prevention of statins against AKI and mortality following cardiac surgery - Do we
      know enough? A trial sequential analysis.

PMID- 27888760
TI  - Relationship between selected DNA polymorphisms and coronary artery disease
      complications.
AB  - BACKGROUND: Coronary heart disease (CHD) development is complex in origin, with
      contributions from well-defined lifestyle and not well-determined genetic risk
      factors. The aim of this study is to report the relationship between certain SNPs
      and the risk of cardiovascular (CV) complications in patients with CAD confirmed
      by coronary angiography. METHODS: In the present study, 1345 subjects with CHD
      were included. The median follow-up period was 8.6years. 19 SNPs were
      investigated for any association with Major Advanced CV Events (MACE), Acute
      Coronary Syndromes (ACS) and Revascularizations. We modeled the 19 SNPs as a
      multilocus genetic risk score (GRS19). RESULTS: During follow-up period, 245
      participants died; 114 due to CV causes. A fatal or non-fatal CV event occurred
      in 882 participants including 214 ACS, 578 revascularizations and 90 strokes. The
      alleles of the following SNPs: rs1746048 (CXCL12), rs9818870 (MRAS) and
      rs17114036 (PPAP2B) were associated with a higher risk of MACE and the alleles of
      SNPs rs1746048 (CXCL12) and rs1122608 (LDLR) were associated with a higher risk
      of revascularization. The alleles of rs12190287 (MRAS), rs121902287 (TCF21) and
      rs2259816 (HNF1a) were associated with a higher risk of ACS. Despite the lack of
      relationship between significant CAD and GRS19, in the top quartile of GRS19
      there was significant relationship between GRS19 and combined endpoint, MACE,
      ACS, and revascularization. CONCLUSIONS: Conclusions. The SNPs of CXCL12 and LDLR
      were associated with risk of revascularization and CXCL12, LPA, MRAS, and PPAP2B
      were associated with the risk of MACE. GRS19 determines CV complications in CAD
      patients with the highest genetic risk score values.

PMID- 27888761
TI  - Tissue thrombin is associated with the pathogenesis of dilated cardiomyopathy.
AB  - BACKGROUND: Thrombin is a serine protease known to be the final product of the
      coagulation cascade. However, thrombin plays other physiological roles in
      processes such as gastric contractions and vessel wound healing, and a state of
      coagulability is increased in patients with dilated cardiomyopathy (DCM). In this
      study, we investigate the role of thrombin in the pathogenesis of DCM. The
      purpose of this study is to clarify the role of thrombin in the pathogenesis of
      DCM and investigate the possibility of treatment against DCM by thrombin
      inhibition. METHODS: We investigated the expression of thrombin in the left
      ventricles of five patients with DCM who underwent the Batista operation and four
      patients without heart disease. Furthermore, we investigated the involvement of
      thrombin in the development of DCM using knock-in mice with a deletion mutation
      of cardiac troponin T that causes human DCM (?K210 knock-in mouse) (B6;129
      Tnnt2tm2Mmto) and assessed the effects of a direct thrombin inhibitor, dabigatran
      on ?K210 knock-in mice using echocardiographic examinations, the Kaplan-Meier
      method and Western blotting. RESULTS: The immunohistochemical analysis showed a
      strong thrombin expression in the DCM patients compared to the patients without
      heart disease. In immunohistochemical analysis, a strong thrombin expression was
      observed in the heart tissues analysis in the ?K210 knock-in mice. Dabigatran
      administration significantly improved fractional shortening according to the
      echocardiographic examination and the survival outcomes in ?K210 knock-in mice.
      CONCLUSION: Tissue thrombin is involved in the pathogenesis of DCM and thrombin
      inhibition can be beneficial for the treatment of DCM.

PMID- 27888762
TI  - Nutritional preconditioning by marine omega-3 fatty acids in patients with ST
      segment elevation myocardial infarction: A METOCARD-CNIC trial substudy.
AB  - BACKGROUND: Marine omega-3 eicosapentaenoic acid (EPA) is readily incorporated
      into cardiomyocyte membranes, partially displacing the omega-6 arachidonic acid
      (AA). Whereas AA is a substrate for pro-inflammatory eicosanoids, the release of
      EPA from cell membranes generates anti-inflammatory lipid mediators, contributing
      to the infarct-limiting effect observed experimental models. Clinical data are
      lacking. METHODS: In this observational study conducted in 100 patients with a
      reperfused anterior ST-elevation myocardial infarction (STEMI), at hospital
      admission we quantified by gas-chromatography the red blood cell proportions of
      AA, EPA, and the AA:EPA ratio, a valid surrogate for cardiomyocyte membrane
      content. Patients underwent cardiac magnetic resonance imaging in the acute phase
      (one week post-STEMI), and at long-term (6 months) follow-up. Infarct size
      (delayed gadolinium enhancement) and cardiac function (left ventricular ejection
      fraction [LVEF]) were correlated with exposures of interest by multivariate
      regression analysis. RESULTS: AA:EPA ratio directly related to acute infarct size
      (coefficient [95% CI]: 6.19 [1.68 to 10.69], P = 0.008) and inversely to long
      term LVEF (coefficient [95% CI]: - 4.02 [- 7.15 to - 0.89], P = 0.012). EPA
      inversely related to acute infarct size (coefficient [95% CI]: - 6.58; [- 11.46
      to - 1.70]; P = 0.009), while a direct association with LVEF at follow-up
      (coefficient [95% CI]: 3.67 [0.25 to 7.08]; P = 0.036) was observed. CONCLUSIONS:
      A low AA:EPA ratio in red blood cells at the time of STEMI is associated with
      smaller acute infarct size and preserved long-term ventricular function. Our
      results are consistent with prior work in experimental models and add to the
      notion of omega-3 fatty acids as a healthy fat. TRIAL REGISTRATION:
      http://www.clinicaltrials.gov/NCT01311700

PMID- 27888763
TI  - Mitral annulus diameter is the main echocardiographic correlate of S3 gallop in
      acute heart failure.

PMID- 27888764
TI  - Clinical characteristics and prognosis of acute coronary syndrome in young women
      and men: A systematic review and meta-analysis of prospective studies.
AB  - OBJECTIVES: The clinical characteristics and prognosis of young women (<=50years)
      with acute coronary syndrome (ACS) are still unclear. METHODS: A total of 5196
      patients with ACS were enrolled from the cardiac center of Chinese PLA General
      Hospital and Anzhen Hospital. The clinical characteristics of these patients were
      analyzed. Then the PubMed, EMBASE, and Cochrane Central Register of Controlled
      Trials electronic databases were searched from January 2001 to July 2016.
      Clinical trials that performed comparisons prognosis of young women versus men
      with ACS were considered for inclusion. RESULTS: The young men had higher BMI,
      had increased incidence of hyperlipidemia, and were more likely to smoke, drink
      alcohol, and have had a previous MI. There was a higher proportion of unstable
      angina (UA) in women than in men (P<0.05). The proportion of thrombolysis
      myocardial infarction (TIMI) 0 in women was lower than in men (P=0.001), and the
      proportion of TIMI 3 was higher in women than in men (P=0.000). The mortality of
      in-hospital, short-term, and long-term rate was significantly higher in women
      than that in men (6.2% vs 2.9%, OR=1.84, P<0.001; 16.4% vs 11.5%, OR=1.66,
      P=0.007; 8.9% vs 3.0%, OR=1.41, P=0.008), but there were no significant
      differences in the rates of major adverse cardiac events (MACE). CONCLUSIONS: In
      young women patients with ACS, the mortality rate during in-hospital, short-term,
      and longer-term follow-up in women was higher than that in men. Thus, young women
      with ACS need more attention during clinical diagnosis and treatment.

PMID- 27888765
TI  - A clinical study on the electrophysiological characteristics of patients without
      recurrence after ablation of persistent atrial fibrillation.
AB  - BACKGROUND: The electrophysiological characteristics of patients without
      recurrence after ablation of persistent atrial fibrillation (AF) have not been
      systematically determined. This study compared the electrophysiological
      characteristics in patients with and without recurrence of AF after persistent AF
      ablation. METHODS: Forty-five patients without recurrence of AF after persistent
      AF ablation were enrolled to assess electrophysiological characteristics
      including pulmonary vein (PV) reconnection, the mitral isthmus (MI) line and the
      roof line reconduction. Ninety-five patients with recurrence of AF after ablation
      were used as the control group. RESULTS: Among patients without recurrence,
      recovery of PV conduction was observed in 37 of 45 (82.2%) patients: 3/45 (6.7%)
      reconnection in 4 veins, 7/45 (15.6%) in 3 veins, 11/45 (24.4%) in 2 veins, and
      16/45 (35.6%) in 1 vein. No significant differences were seen in the proportion
      of patients with PV reconnection compared to patients with recurrence (p>0.05).
      Among patients without recurrence, the MI line reconduction was observed in 3/45
      (6.7%) patients; the roof line conduction was observed in 5/45 (11.1%) patients.
      In comparison, patients with clinical recurrence of AF had recovery of the MI
      line conduction in 27/95 (28.4%) and recovery of the roof line conduction in
      26/95 (27.4%). Significant differences were seen between these two groups (6.7%
      vs 28.4%, p=0.004; 11.1% vs 27.4%, p=0.031). CONCLUSION: Although a high
      incidence of PV reconnection was similarly observed in patients with and without
      recurrence of AF, a lower incidence of lines reconduction was observed in
      patients without recurrence of AF.

PMID- 27888767
TI  - One of these things is not like the others: Testing trajectories in drinking
      frequency, drinking quantity, and alcohol-related problems in undergraduate
      women.
AB  - Alcohol misuse is an increasingly common problem in undergraduate women. Building
      upon research suggesting that maturing out of risky patterns of alcohol use can
      occur, our study tested how three facets of alcohol use change differentially
      over time in undergraduate women. A sample of 218 undergraduate women (M
      age=20.6years) participated in a four-wave, 18-month longitudinal study measuring
      frequency of alcohol consuming occasions, quantity of alcohol consumed per
      occasion, and alcohol-related problems. Growth curve analyses showed that alcohol
      frequency remained stable over 18months, whereas alcohol quantity and problems
      decreased over time. Results indicate undergraduate women are drinking with
      similar frequency over time, but they are drinking a smaller quantity of alcohol
      per drinking occasion and they are experiencing fewer alcohol-related problems.
      Findings help clarify the maturity principle by showing a different pattern of
      drinking as undergraduate women age that involves lower quantities of alcohol per
      drinking occasion and less problematic alcohol use, but not necessarily less
      frequent drinking.

PMID- 27888766
TI  - Circadian time-dependent antioxidant and inflammatory responses to acute cadmium
      exposure in the brain of zebrafish.
AB  - Up to date, little information is available on effects of circadian rhythm on
      metal-induced toxicity in fish. In this study, zebrafish were acutely exposed to
      0.97mgL-1 cadmium for 12h either at ZT0 (the light intensity began to reached
      maximum) or at ZT12 (light intensity began to reached minimum) to evaluate the
      temporal sensitivity of oxidative stress and inflammatory responses in the brain
      of zebrafish. Profiles of responses of some genes at mRNA, protein and activity
      levels were different between ZT0 and ZT12 in the normal water. Exposure to Cd
      induced contrary antioxidant responses and similar inflammatory responses between
      ZT0 and ZT12. However, the number of inflammatory genes which were up-regulated
      was significantly greater at ZT12 than at ZT0. And, the up-regulated inflammatory
      genes were more responsive at ZT12 than at ZT0. At ZT12, antioxidant genes were
      down-regulated at mRNA, protein and activity levels. Contrarily, antioxidant
      genes were not affected at mRNA levels but activated at the protein and/or
      activity levels at ZT0. Reactive oxygen species (ROS) sharply increased and
      remained relatively stable when fish were exposed to Cd at ZT12 and ZT0,
      respectively. Positive correlations between ROS levels and mRNA levels of nuclear
      transcription factor kappaB (NF-kappaB) and between mRNA levels of NF-kappaB and
      its target genes were observed, suggesting that ROS may play an essential role in
      regulating the magnitude of inflammatory responses. Taken together, oxidative
      stress and immunotoxicity in the brain were more serious when fish were exposed
      to Cd in the evening than in the morning, highlighting the importance of
      circadian rhythm in Cd-induced neurotoxicity in fish.

PMID- 27888768
TI  - Multiple myeloma treatment at relapse after autologous stem cell transplantation:
      A practical analysis.
AB  - Over the past decade, significant advances have been made in the field of
      multiple myeloma. Introduction of the so-called novel agents, proteasome
      inhibitors (PI) and immunomodulatory drugs (IMiD), and improved supportive care
      have resulted in significantly better outcome. Standard first line treatment in
      fit patients include PI and IMiD based induction, high dose melphalan with
      autologous hematopoietic stem cell transplantation (ASCT) and
      consolidation/maintenance. However, despite these progresses MM remains incurable
      for the majority of patients and most patients will relapse. Next generation PI
      (carfilzomib, ixazomib) and IMiD (pomalidomide) and new therapeutic classes:
      monoclonal antibody (elotuzumab, daratumumab) and pan-deacetylase inhibitors
      (panobinostat) have been successfully evaluated in relapse multiple myeloma. Some
      of these new agents are now approved for multiple myeloma treatment at relapse.
      However choosing the most appropriate treatment at relapse may be difficult. This
      review sum up the most important studies and provide evidence to choose the most
      relevant therapeutic strategy for relapse after ASCT, based on disease, patient
      and previous treatment related parameters.

PMID- 27888769
TI  - A first described case of cancer-associated non-bacterial thrombotic endocarditis
      in the era of direct oral anticoagulants.

PMID- 27888770
TI  - The effect of the disulfideisomerase domain containing protein in the defense
      against polyhexamethylene biguanide of highly tolerant Acanthamoeba at the
      trophozoite stage.
AB  - Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing a
      blinding keratitis and fatal granulomatous encephalitis. Current treatment
      generally involves an hourly application of polyhexamethylene biguanide (PHMB)
      over a period of several days but this is not entirely effective against all
      strains/isolates. The tolerance mechanisms of PHMB in Acanthamoeba cells remain
      unclear. In this study, we found that the mRNA expression level of
      disulfideisomerase domain containing protein (PDI) increased rapidly in surviving
      cells of the highly PHMB-tolerant Acanthamoeba castellanii strain, NCKH_D, during
      PHMB treatment, but not in the ATCC standard strain. After PDI-specific
      silencing, NCKH_D was found to be more vulnerable to PHMB treatment. The results
      described above show that PDI is an important gene for PHMB tolerance ability in
      a highly PHMB-tolerant strain of Acanthamoeba and provide a new insight for more
      efficient medicine development for Acanthamoeba keratitis.

PMID- 27888771
TI  - Increased anxiety-like behaviors, but blunted cortisol stress response after
      neonatal hippocampal lesions in monkeys.
AB  - The hippocampus is most notably known for its role in cognition and spatial
      memory; however it also plays an essential role in emotional behaviors and
      neuroendocrine responses. The current study investigated the long-term effects of
      neonatal hippocampal lesions (Neo-Hibo) on emotional and hypothalamic-pituitary
      adrenal (HPA) axis functioning. During infancy, unlike controls, Neo-Hibo monkeys
      exhibited enhanced expression of emotional behaviors (e.g. freezing, anxiety
      like, and self-directed behaviors) when exposed to a human intruder (HI task).
      Upon reaching adulthood, they exhibited reduced freezing and hostility, but
      increased anxiety-like and self-directed behaviors during the HI task. Neo-Hibo
      monkeys behaved as if they systematically over-rated the risk inherent in the HI
      task, which supports Gray and McNaughton's septo-hippocampal theory of anxiety.
      Also, in adulthood, the increased levels of anxiety-like behaviors in Neo-Hibo
      monkeys were associated with a blunted cortisol response to the HI task.
      Examination of basal HPA axis function revealed that Neo-Hibo monkeys exhibited
      the typical diurnal cortisol decline throughout the day, but had lower cortisol
      concentrations in the morning as compared to controls. Taken together these data
      suggest that an intact hippocampus during development plays a larger role beyond
      that of inhibitory/negative feedback regulation of the HPA axis stress
      activation, and may be critical for HPA axis basal functioning as well as for the
      stress response. The behavioral and neuroendocrine changes demonstrated in the
      current study are reminiscent of those seen in human or nonhuman primates with
      adult-onset hippocampal damage, demonstrating little functional compensation
      following early hippocampal damage.

PMID- 27888774
TI  - Prediction of sodium content in commercial processed meat products using near
      infrared spectroscopy.
AB  - The present study evaluated the ability of near infrared transmittance (NIT)
      spectroscopy (FoodScan, 850-1050nm) to predict sodium (Na) content in commercial
      processed meat products (n=310) as intact and ground samples. Prediction models
      were built with all samples spectra and with spectra divided in 5 categories
      according to the manufacturing meat process. Sodium content (%) was determined
      using inductively coupled plasma optical emission spectrometry. Modified partial
      least squares regression for the overall samples showed satisfactory predictive
      ability for intact (coefficient of determination in cross-validation, R2CV=0.93)
      and ground samples (R2CV=0.95). Despite the low number of samples, good specific
      prediction models were developed for each commercial meat category. In
      conclusion, NIT is really promising for at-line application to predict Na in
      processed meat products which could help industry to accomplish the new labelling
      regulation.

PMID- 27888773
TI  - The combined effects of grain supplementation and tenderstretching on alpaca
      (Vicugna pacos) meat quality.
AB  - This study investigated the effects of feeding a mixed grain supplement and
      tenderstretching (TS) alpaca carcasses on meat quality. A total of 56 castrated
      24month old alpacas were divided into two treatments (pasture-only, and pasture
      plus supplementation). Supplemented groups were fed a mixed grain ration in
      addition to ad lib pasture for 10weeks. Animals were slaughtered across two kill
      days (n=28). One half of each carcass was suspended by the pelvis (TS) prior to
      chilling, and the other half was Achilles tendon hung (AH). After 24h, muscles
      were removed and aged for 10 and 25d. TS significantly increased sarcomere length
      and reduced shear force and cooking loss in the m. semimembranosus. This trend
      was not observed in other muscles including the m. longissimus thoracis et
      lumborum (LL) and m. psoas major. Ageing period resulted in a marginal
      improvement in LL tenderness. There is clear evidence that TS improves tenderness
      in the hindquarter of alpacas.

PMID- 27888772
TI  - Adrenocortical sensitivity, moderated by ongoing stress, predicts drinking
      intensity in alcohol-dependent men.
AB  - Allostatic load from both environmental stressors and persistent glucocorticoid
      secretion has been associated with disease severity in alcohol dependence.
      Heightened relapse risk and/or drinking severity, in particular, may be a
      reaction to alcohol- and withdrawal-induced changes in physiological stress
      response systems coupled with ongoing life stress, although their shared
      contributions upon drinking severity have not been assessed. To investigate the
      combined contribution of hypothalamic-pituitary-adrenal (HPA) reactivity and
      environmental stressors (e.g., ongoing life stress) to relapse severity in
      alcohol-dependent men following treatment, plasma adrenocorticotropin (ACTH) and
      cortisol were obtained in 4-6 weeks abstinent alcohol-dependent men (n=41)
      following a psychosocial stressor [the Trier Social Stress Test (TSST)] and two
      pharmacological provocations [ovine corticotropin releasing factor (oCRH) and
      cosyntropin]. Following treatment discharge, drinking outcomes (primary outcome:
      drinks per drinking day (DDD); secondary outcomes: total drinks and drinking
      days) were assessed weekly and ongoing life stress was assessed biweekly for 24
      weeks following treatment discharge. Generalized estimating equation models of
      drinking severity were fit with basal and stimulated ACTH and cortisol
      concentrations as predictors and ongoing life stress as the moderator. Greater
      levels of life stress were independently associated with greater drinking
      intensity (DDD and total drinks) but not frequency (days drinking). Higher basal
      cortisol:ACTH or provoked cortisol:ACTH ratios were strongly associated with
      greater post-treatment DDD in individuals who experienced higher levels of
      ongoing stress. In conclusion, ongoing life stress is associated with post
      treatment drinking intensity in alcohol dependent men; stress also strengthens
      the relationship between adrenocortical sensitivity and post-treatment drinking.
      Physiological measures of allostatic load and environmental stressors conjointly
      increase relapse intensity.

PMID- 27888775
TI  - Cost, energy, global warming, eutrophication and local human health impacts of
      community water and sanitation service options.
AB  - We compared water and sanitation system options for a coastal community across
      selected sustainability metrics, including environmental impact (i.e., life cycle
      eutrophication potential, energy consumption, and global warming potential),
      equivalent annual cost, and local human health impact. We computed normalized
      metric scores, which we used to discuss the options' strengths and weaknesses,
      and conducted sensitivity analysis of the scores to changes in variable and
      uncertain input parameters. The alternative systems, which combined centralized
      drinking water with sanitation services based on the concepts of energy and
      nutrient recovery as well as on-site water reuse, had reduced environmental and
      local human health impacts and costs than the conventional, centralized option.
      Of the selected sustainability metrics, the greatest advantages of the
      alternative community water systems (compared to the conventional system) were in
      terms of local human health impact and eutrophication potential, despite large,
      outstanding uncertainties. Of the alternative options, the systems with on-site
      water reuse and energy recovery technologies had the least local human health
      impact; however, the cost of these options was highly variable and the energy
      consumption was comparable to on-site alternatives without water reuse or energy
      recovery, due to on-site reuse treatment. Future work should aim to reduce the
      uncertainty in the energy recovery process and explore the health risks
      associated with less costly, on-site water treatment options.

PMID- 27888776
TI  - Bioavailable phosphorus (P) reduction is less than mobile P immobilization in
      lake sediment for eutrophication control by inactivating agents.
AB  - Phosphorus (P) immobilization by inactivating agents in the sediment of eutrophic
      lakes to reduce immediately available P in lake water is often crucial for
      mitigating nuisance eutrophication symptoms, such as cyanobacterial blooms.
      Macrophytes and phytoplankton, however, can directly utilize P from the sediment
      for growth. Accordingly, a comprehensive analysis of the P bioavailability in
      lake sediment amended with two promising P-inactivation agents, namely
      Phoslock(r) and drinking water treatment residue (DWTR), was investigated in both
      short- and long-term studies (20 and 180 d). Phosphorus-availability was assessed
      using six chemical extraction methods and Hydrilla verticillata and Microcystis
      aeruginosa growth tests. The results showed that Phoslock(r) and DWTR
      significantly reduced mobile P (NH4Cl and Na2S2O4/NaHCO3 extractable P) in lake
      sediment, while P bioavailability that was assessed by different methods showed
      considerable deviations. Interestingly, appropriate bioavailable P chemical
      extraction methods were determined based on linear correlation analysis, and
      further comparison indicated that reduction of bioavailable P by DWTR (<55% for
      macrophyte available P) and Phoslock(r) (<17% for cyanobacteria available P) were
      clearly less than the mobile P immobilization (>75%) at recommended dosages,
      which was probably caused by the capability of macrophyte and cyanobacteria to
      utilize various fractions of P (except the residual P) in amended sediment under
      proper illumination. Therefore, DWTR and Phoslock(r) can effectively reduce P
      release from lake sediment, but the potential bioavailable P may pose
      uncertainties for eutrophication control in lakes that typically have regular
      sediment re-suspension. Overall, an evaluation of the bioavailable P pool in the
      lake ecosystem should be essential for successful lake geo-engineering.

PMID- 27888777
TI  - The effects of prenatal testosterone on wages: Evidence from Russia.
AB  - Is in utero exposure to testosterone correlated with earnings? The question
      matters for understanding determinants of wage differences that have attracted so
      much attention among economists in the past decade. Evidence indicates that
      markers for early testosterone exposure are correlated with traits like risk
      taking and aggressiveness. But it is not at all clear how such findings might map
      into labor market success. We combine unique data from the Russian Longitudinal
      Monitoring Survey with measured markers (2D:4D ratios) for testosterone exposure
      and find that lower digit ratios (higher T) correlate with higher wages for women
      and for men, when controlling for age, education and occupation. There is also
      some evidence of a potential non-linear, inverse U-effect of digit ratios on
      wages but this is sensitive to choice of specification. These findings are
      consistent with earlier work on prenatal T and success in careers (Coates et al.,
      2009) but inconsistent with the work of Gielen et al. (2016) who find differing
      effects for men and women.

PMID- 27888779
TI  - Adverse remodeling of the obtuse marginal artery in compensatory hypertrophied
      myocardium from spontaneously hypertensive rats.
AB  - BACKGROUND: Spontaneously hypertensive rats (SHR) serve as a model of genetic
      hypertension. Adverse remodeling of a coronary artery has been reported in SHR.
      This model is used to study new therapies in regression vascular remodeling.
      However, no data are available that show remodeling of the intramyocardial branch
      of the obtuse marginal artery in 10-month-old SHR. This study was designed to
      assess remodeling (changes in vascular structure and fibrosis) of this coronary
      artery. METHODS AND RESULTS: The study was performed on 10-month-old male SHR
      (n=7) and normotensive control Wistar Kyoto rats (WKY) (n=7). Using histology, we
      show that the external diameter, lumen diameter, wall width, and cross-sectional
      area of the intramyocardial artery were significantly greater in SHR than in WKY.
      The wall-to-lumen ratio was similar in SHR and WKY. The collagen volume density
      of the intramyocardial artery in SHR was significantly greater than in WKY.
      CONCLUSIONS: Our results show hypertrophic outward remodeling in the
      intramyocardial branch of the obtuse marginal artery of the left ventricle in
      SHR. This artery can serve as a new vascular bed from adult SHR to study novel
      therapies in regression coronary artery remodeling.

PMID- 27888778
TI  - Loss of mechanical directional dependency of the ascending aorta with severe
      medial degeneration.
AB  - Biomechanical characterization of the aortic wall may help risk stratify patients
      with aneurysms. We investigated the degree of anisotropy, the directional
      dependency of mechanical properties, in control and aneurysmal ascending aortic
      tissue. We hypothesized that medial degeneration and aortic wall remodeling as
      found in aneurysmal tissue alter energy loss in both the circumferential and
      longitudinal directions, thereby reducing anisotropy. Aneurysmal and control
      ascending aortic tissue excised during surgery was subjected to biaxial tensile
      testing. Stress-strain relationships were collected in the circumferential and
      longitudinal directions; from these data, the mechanical properties of energy
      loss and the apparent modulus of elasticity were derived, and the associated
      anisotropy indices were calculated. Movat pentachrome histological staining was
      performed, and aortic wall medial degeneration was quantified. Energy loss was
      greater in the circumferential than the longitudinal direction, demonstrating
      significant anisotropy in both normal and aneurysmal aortas (P<.0001). This
      directional dependency diminished in (a) larger aortas (r2=0.15, P=.01),
      especially when indexed to body surface area (r2=0.29, P=.002); (b) aortas with
      greater overall energy loss (r2=0.44, P<.0001); (3) aortas associated with
      tricuspid valves (P=.004); and (4) higher collagen-to-elastin ratio (r2=0.29,
      P=.001). Aortas with collagen-to-elastin ratios greater than 2 were uniformly
      isotropic. Furthermore, the greatest energy loss anisotropy was found on the
      inner curvature of the aorta (P=.01). Energy loss demonstrates the directional
      dependency of aortic tissue. Energy loss isotropy is associated with medial
      degeneration, indicating that microstructural changes can be captured by global
      biomechanics, thereby identifying it as a marker of disease severity.

PMID- 27888780
TI  - Investigations of the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) binary van der Waals
      complexes: ab initio intermolecular potential energy surfaces, vibrational states
      and predicted pure rotational transition frequencies.
AB  - The intermolecular potential energy surfaces (PESs) of the ground electronic
      state for the Rg-BrCl (Rg=He, Ne, Ar, Kr, Xe) van der Waals complexes have been
      constructed by using the coupled-cluster method in combination with the augmented
      quadruple-zeta correlation-consistent basis sets supplemented with an additional
      set of bond functions. The features of the anisotropic PESs for these complexes
      are remarkably similar, which are characterized by three minima and two saddle
      points between them. The global minimum corresponds to a collinear Rg-Br-Cl
      configuration. Two local minima, correlate with an anti-linear Rg-Cl-Br geometry
      and a nearly T-shaped structure, can also be located on each PES. The quantum
      bound state calculations enable us to investigate intermolecular vibrational
      states and rotational energy levels of the complexes. The transition frequencies
      are predicted and are fitted to obtain their corresponding spectroscopic
      constants. In general, the periodic trends are observed for this complex family.
      Comparisons with available experimental data for the collinear isomer of Ar-BrCl
      demonstrate reliability of our theoretical predictions, and our results for the
      other two isomers of Ar-BrCl as well as for other members of the complex family
      are also anticipated to be trustable. Except for the collinear isomer of Ar-BrCl,
      the data presented in this paper would be beneficial to improve our knowledge for
      these experimentally unknown species.

PMID- 27888781
TI  - Stabilization of cytochrome b5 by a conserved tyrosine in the secondary sphere of
      heme active site: A spectroscopic and computational study.
AB  - Heme proteins perform a large array of biological functions, with the heme group
      bound non-covalently or covalently. To probe the stabilization role of conserved
      tyrosine residue in the secondary sphere of heme site in heme proteins, we herein
      used cytochrome b5 (Cyt b5) as a model protein, and mutated Tyr30 to Phe or His
      by removal of Tyr30 associated H-bond network and hydrophobic interaction. We
      performed thermal-induced unfolding studies for the two mutants, Y30F Cyt b5 and
      Y30H Cyt b5, as monitored by both UV-Vis and CD spectroscopy, as well as heme
      transfer studies from these proteins to apo-myoglobin, with wild-type Cyt b5
      under the same conditions for comparison. The reduced stability of both mutants
      indicates that both the H-bonding and hydrophobic interactions associated with
      Tyr30 contribute to the protein stability. Moreover, we performed molecular
      modeling studies, which revealed that the hydrophobic interaction in the local
      region of Y30F Cyt b5 was well-remained, whereas Y30H Cyt b5 formed an H-bond
      network. These observations suggest that the conserved Tyr30 in Cyt b5 is not
      replaceable due to the presence of both the H-bond network and hydrophobic
      interaction in the secondary sphere of the heme active site. As demonstrated here
      for Cyt b5, it may be of practical importance for design of artificial heme
      proteins by engineering a Tyr in the secondary sphere with improved properties
      and functions.

PMID- 27888782
TI  - Effect of smoking cessation in saliva compounds by FTIR spectroscopy.
AB  - INTRODUCTION: Smoking is currently considered one of the biggest risk factors for
      the development of various diseases and early death. Fourier transform infrared
      (FTIR) spectroscopy is a valuable tool for analysis of biofluids such as saliva
      and is considered useful for diagnostic purposes. The aim of this study was to
      evaluate the effect of smoking cessation on saliva composition by FTIR
      spectroscopy. METHODS: We analyzed the saliva of participants in two groups: a
      smoker group made up of 10 chronic smokers and a former smoker group made up of
      10 individuals who had stopped smoking. Members of both groups had similar
      smoking history. RESULTS: The results showed few differences in spectral
      intensity between the groups; however, spectral peaks were slightly increased in
      the group of smokers in the bands for DNA, indicating modification of its content
      or cell necrosis. They were also increased for the mannose-6-phosphatase
      molecule, which is expressed in prostate and breast carcinomas. In the former
      smoker group, the peak of thyociante was decreased and the band referring to
      collagen increased in intensity, which indicates a better tissue regeneration
      capacity. CONCLUSION: Considering these results and the fact that tobacco intake
      was similar between the groups, it can be concluded that there was recovery of
      tissue regeneration capacity with smoking cessation during the study period,
      although the effects found in smokers persisted in the bodies of those who had
      given up smoking.

PMID- 27888783
TI  - A dual analyte fluorescent chemosensor based on a furan-pyrene conjugate for Al3+
      & HSO3.
AB  - A simple chalcone based dual analyte fluorescent probe FPC for Al3+ and HSO3-
      ions was developed. FPC detects both the analytes through a "turn off-on"
      approach and by the PET and ICT mechanism. FPC showed high selectivity and
      sensitivity for Al3+ and HSO3- ions detection over other interfering and
      competing metal ions. In addition, the LOD of FPC for sensing Al3+ and HSO3- ions
      was found to be 1.60*10-7M and 0.17*10-6M respectively. An electrochemical
      desalination technique was employed for the complete removal of Al3+ ions from
      the environmental water samples by using the probe FPC.

PMID- 27888784
TI  - The influence of a preceptor-student 'Daily Feedback Tool' on clinical feedback
      practices in nursing education: A qualitative study.
AB  - BACKGROUND: Feedback in clinical education is essential for the development of
      competent nurses. When the process is enacted well, it offers measured
      performance against standards required by the nursing health profession,
      promoting learning and behavioural change. Despite this, health literature
      describes numerous barriers to effective feedback processes. OBJECTIVE: A
      qualitative descriptive design was used to determine whether the introduction of
      a Daily Feedback Tool addressing some of the barriers to effective feedback,
      influenced nursing students and clinical supervisors (preceptors) experiences in
      nursing clinical education. METHOD: A total of eight semi-structured focus groups
      related to student and preceptors reported experiences were completed comprising
      of preceptor and student groups independently. The data was analysed using
      aspects of grounded theory including purposive sampling and system analysis
      informing the subsequent stages of data collection. RESULTS: Participants
      reported that the introduction of the Daily Feedback Tool overcame some of the
      reported barriers, particularly relating to the frequency of feedback occasions,
      and the traditionally didactic, teacher-led feedback conversations. CONCLUSION:
      The Daily Feedback Tool was reported to influence the development of trusting
      preceptor-student relationships which gave the learner agency to seek feedback
      promoting learning and overall performance.

PMID- 27888785
TI  - Hallux varus following scarf osteotomy.
AB  - Hallux varus is an uncommon condition and majority of the cases are iatrogenic.
      It can occur as a result of any type of hallux valgus correction surgery and in
      our cases scarf osteotomy is not an exception. Treatment of this complication can
      be challenging and it is important to understand the factors that cause this
      deformity before embarking on surgical correction. Four cases of hallux varus
      following Scarf osteotomy (1% of our total Scarf osteotomy cases) and discuss the
      salient features of these patients. The authors ascertained the factors that
      caused iatrogenic hallux varus and formulated a classification of the nature of
      the deformity. The management of iatrogenic hallux varus based on our experience
      and proposed classification system has also been outlined and discussed.

PMID- 27888786
TI  - The assessment of three-dimensional foot pronation using a principal component
      analysis method in the stance phase of running.
AB  - Foot pronation has not been quantified dynamically in three planes of movement in
      an in-vivo study. The aims of this study were to determine foot pronation through
      using Principal Component Analysis (PCA) method and to compare it among barefoot,
      shod and shod with 6 degrees  lateral wedge during the stance phase of running.
      In this method, three-dimension of foot movements were measured and each of these
      components represents a percentage of foot pronation. These components were
      derived based on eigenvalues and vectors of covariance matrix of primary
      variables. The first (PC1), second (PC2) and third (PC3) components explained
      about (82.5%, 79.1%), (14%, 15.8%) and (3.5%, 5.1%) the foot pronation for
      barefoot and shod conditions, respectively. These components were mutually
      independent and the components set had the same information as the primary
      variables. Foot pronation index and eversion angles were calculated and compared
      among barefoot, shod and shod with wedge insole (6 degrees  lateral wedge insole)
      conditions in the four phases of stance. Statistical analysis showed that there
      was no foot conditions effect for foot eversion in four phases (p=0.72), while
      this effect was significant for PC1 (p=0.001). This finding shows that PC1 index
      could discriminate footwear effect among each phase of stance. Specifically,
      pronation was reduced in shoe condition as compared to barefoot condition
      (p=0.02) from 5 to 50% of stance phase. It has been suggested that the PCA method
      provides more accurate criteria for investigating effects of footwear
      interventions on simultaneous three-dimensional foot motion.

PMID- 27888787
TI  - Outcomes in chevron osteotomy for Hallux Valgus in a large cohort.
AB  - Clinical and radiological related outcomes have been reported for Chevron
      osteotomy as correction for mild to moderate hallux valgus, but only for
      relatively small patient series. Moreover, evaluation of the patient's point of
      view has mostly been conducted by means of more physician-based outcome measures.
      The goal of this study was to evaluate the effect of the Chevron osteotomy for
      hallux valgus on patients' daily lives using the Foot and Ankle Outcome Score
      (FAOS) as a validated and a hallux valgus specific patient reported outcome
      measure (PROM). Secondary outcome measures were radiological correction,
      complication rate, and re-operations. All 438 Chevron procedures (336 patients),
      at two surgical hospital sites in the period between January 2010 and October
      2014, were retrospectively evaluated with a follow-up of at least 6 months.
      Patients were invited to fill in a cross-sectional online FAOS. For the FAOS, a
      total response of 60% was achieved. The FAOS ranged between 71 and 88 with a
      follow-up of on average 36 months. Patients with an undercorrection of their
      hallux valgus (11.6% of the procedures) scored significantly lower on three
      subscales of the FAOS (range between 61 and 77 versus 72-84). Patients who had a
      reoperation (12.6% of the procedures) also scored significantly lower on four
      subscales: 58-100 versus 73-89. Postoperative radiological measurements improved
      significantly with a mean difference of 6.1 (5.9; 6.4) degrees for the
      intermetatarsal angle and 13.7 (13.0; 14.5) degrees for the hallux valgus angle.
      In this large study cohort, Chevron osteotomy for hallux valgus offers good PROM
      scores on FAOS. These scores were significantly lower in patients with
      radiological undercorrection or with a reoperation. Results of the FAOS appear to
      modulate with physician based outcomes and therapeutic incidents. Improvement of
      outcome may therefore well be possible by increased attention on these surgical
      details.

PMID- 27888788
TI  - Alternate hot and cold application in the management of heel pain: A pilot study.
AB  - BACKGROUND: Despite a long-standing tradition of naturopathic physical therapy
      and hydrotherapy use in the treatment of musculoskeletal conditions, neither
      naturopathy, nor specific aspects of hydrotherapy have been tested for efficacy
      in the treatment of heel pain. METHODS: Patients (n=20) were assigned to standard
      naturopathic physiotherapy care (NPC) with two adjuvant therapy groups: a control
      group (therapeutic ultrasound, n=10), or alternating compresses (n=10). Pain
      scores were measured before and after treatment using Visual Analog Scale (VAS)
      and foot functionality was measured using the Foot Function Index (FFI). RESULTS:
      FFI reduced from 46.97 to 31.98 (p=0.005) among normal protocol patients and from
      49.72 to 21.35 (p=<0.001) among patients receiving the alternating compress
      protocol. Average VAS pain intensity in the seven days of treatment decreased
      from 3.53 to 2.53cm (p=<0.001) among patients receiving NPC and from 4.09 to
      2.61cm (p=<0.001) amongst those receiving NPC plus alternating compresses. There
      was no significant difference in pain score reduction between the two groups
      (p=0.206), but patients with alternating compresses as part of their treatment
      had significant improvements in foot functionality (p=0.007). DISCUSSION:
      Naturopathic physical therapy significantly improves foot functionality and pain
      scores in heel pain. Additionally, alternating compresses improve foot
      functionality scores.

PMID- 27888789
TI  - Reliability and minimal detectable change in foot pressure measurements in
      typically developing children.
AB  - BACKGROUND: In pedobarography, clinically meaningful comparison of measurements
      within or between subjects is limited by data variability and measurement error.
      This study aims to determine the components of the minimal detectable change
      (MDC) in impulse across all foot regions and the reliability of these measures.
      METHODS: A convenience sample of foot pressures from 108 visits by normal,
      healthy subjects aged 2-17 years was studied. Each subject had three
      pedobarograph measurements taken per foot, with six subjects returning for a
      second visit for assessment of day-to-day variability. Using a five-region mask,
      segmental impulses were determined, and from these we obtained the coronal plane
      pressure index (CPPI). Inter-rater, intra-rater, and day-to-day data were
      analyzed using intraclass correlation coefficients (ICC) to quantify reliability.
      Variability of the data was analyzed to quantify the MDC. RESULTS: Inter- and
      intra-rater reliability was high for all measurements while variability was low,
      indicating small direct measurement error. Generally, the largest contributing
      factor to the MDC was day-to-day variability. Step-to-step variability was more
      dependent on foot segment than age although minor age-related changes were noted.
      Finally, the high relative variability in the CPPI and the medial mid foot
      impulse resulted in very high MDCs for these measures.

PMID- 27888790
TI  - Complication assessment and prevention strategies using midfoot fusion bolt for
      medial column stabilization in Charcot's osteoarthropathy.
AB  - In Charcot's osteoarthropathy stabilization of the medial column of the foot was
      introduced in order to establish a stable foot and reduce the risk for
      amputation. This study was performed to analyze postoperative complications,
      define risk factors for those and develop strategies for prevention. Since bolt
      dislocation takes place frequently, it was aimed to predict an appropriate time
      point for bolt removal under the condition that osseous healing has occurred.
      Fourteen consecutive patients with neuroosteoarthropathy of the foot and arch
      collapse were treated with open reduction and stabilization using midfoot fusion
      bolt and lateral lag screws. Age, gender, presence of preoperative osteomyelitis
      or ulcer, number of complications and operative revisions, Hba1c value,
      consolidation of arthrodesis, presence of a load-bearing foot and period to bolt
      dislocation was assessed. The mean follow-up was 21.4+/-14.6 (mean+/-SDM) months,
      64% of patients suffered from diabetes with a preoperative Hba1c of 8.5+/-2.4.
      The mean number of revisions per foot was 3.6+/-4.1. Bolt dislocation was seen in
      57% of the patients following 11.3+/-8.5 months; in 75% of these patients bony
      healing occurred before dislocation. There was a significant association between
      preoperative increased Hba1c value, presence of preoperative ulcer and wound
      infection. Healing of arthrodesis was demonstrated in 57% and a permanent weight
      bearing foot without recurrent ulcer was achieved in 79%. The early and late
      postoperative complications could be controlled in general. A fully load-bearing
      and stable foot was obtained, despite osseous consolidation was not detected in
      all of these cases. Once a stable foot has established early removal of fusion
      bolt should be considered. To decrease the risk of infection Hba1c should be
      adjusted and ulcers should be treated before the operation.

PMID- 27888791
TI  - Influence of genetic variations in platelet glycoproteins and eNOS in the
      development of arterial ischaemia of lower limbs in type 2 diabetes mellitus
      patients.
AB  - Endothelial and platelet dysfunction increase the atherothrombotic risk in
      diabetes mellitus patients. Therefore, arterial ischaemia of lower limbs is an
      important complication in diabetes mellitus. In the present work, type 2 diabetic
      patients were classified by a podiatrist into presence or absence of arterial
      ischaemia of lower limbs. Several polymorphisms in platelet glycoproteins and
      eNOS genes were evaluated. Our results suggest that the -5CC genotype in Kozak
      sequence of GPIbalpha may be associated with a higher risk of developing arterial
      ischaemia of lower limbs in type 2 diabetes mellitus patients.

PMID- 27888792
TI  - Case Study: An intraoperative finding of black bone disease in a podiatric
      surgery patient.
AB  - Black bone disease has been recognised as a potential consequence of long-term
      treatment with tetracycline antibiotics. Largely documented affecting structures
      in the head and skull, there are few reported cases of black bone disease in the
      foot and ankle. The case of a 55 years old patient, who as a teenager, had
      undergone treatment with minocycline hydrochloride for chronic acne, and was
      found to have bone discolouration consistent with minocycline induced black bone
      disease (MIBBD) during the course of hallux valgus corrective surgery some 40
      years later, is presented. In spite of the intraoperative findings, the patient's
      post-operative recovery and bone healing was uneventful. The literature on
      minocycline induced black bone disease is reviewed.

PMID- 27888793
TI  - InverPep: A database of invertebrate antimicrobial peptides.
AB  - OBJECTIVES: The aim of this work was to construct InverPep, a database
      specialised in experimentally validated antimicrobial peptides (AMPs) from
      invertebrates. METHODS: AMP data contained in InverPep were manually curated from
      other databases and the scientific literature. MySQL was integrated with the
      development platform Laravel; this framework allows to integrate programming in
      PHP with HTML and was used to design the InverPep web page's interface. InverPep
      contains 18 separated fields, including InverPep code, phylum and species source,
      peptide name, sequence, peptide length, secondary structure, molar mass, charge,
      isoelectric point, hydrophobicity, Boman index, aliphatic index and percentage of
      hydrophobic amino acids. CALCAMPI, an algorithm to calculate the physicochemical
      properties of multiple peptides simultaneously, was programmed in PERL language.
      RESULTS: To date, InverPep contains 702 experimentally validated AMPs from
      invertebrate species. All of the peptides contain information associated with
      their source, physicochemical properties, secondary structure, biological
      activity and links to external literature. Most AMPs in InverPep have a length
      between 10 and 50 amino acids, a positive charge, a Boman index between 0 and 2
      kcal/mol, and 30-50% hydrophobic amino acids. InverPep includes 33 AMPs not
      reported in other databases. Besides, CALCAMPI and statistical analysis of
      InverPep data is presented. The InverPep database is available in English and
      Spanish. CONCLUSIONS: InverPep is a useful database to study invertebrate AMPs
      and its information could be used for the design of new peptides. The user
      friendly interface of InverPep and its information can be freely accessed via a
      web-based browser at
      http://ciencias.medellin.unal.edu.co/gruposdeinvestigacion/prospeccionydisenobiom
      leculas/InverPep/public/home_en.

PMID- 27888794
TI  - Custom FPGA processing for real-time fetal ECG extraction and identification.
AB  - Monitoring the fetal cardiac activity during pregnancy is of crucial importance
      for evaluating fetus health. However, there is a lack of automatic and reliable
      methods for Fetal ECG (FECG) monitoring that can perform this elaboration in real
      time. In this paper, we present a hardware architecture, implemented on the
      Altera Stratix V FPGA, capable of separating the FECG from the maternal ECG and
      to correctly identify it. We evaluated our system using both synthetic and real
      tracks acquired from patients beyond the 20th pregnancy week. This work is part
      of a project aiming at developing a portable system for FECG continuous real-time
      monitoring. Its characteristics of reduced power consumption, real-time
      processing capability and reduced size make it suitable to be embedded in the
      overall system, that is the first proposed exploiting Blind Source Separation
      with this technology, to the best of our knowledge.

PMID- 27888795
TI  - Targeting tachykinin receptors in neuroblastoma.
AB  - Neuroblastoma is the most common extracranial tumor in children. Despite
      aggressive multimodal treatment, high-risk neuroblastoma remains a clinical
      challenge with survival rates below 50%. Adding targeted drugs to first-line
      therapy regimens is a promising approach to improve survival in these patients.
      TACR1 activation by substance P has been reported to be mitogenic in cancer cell
      lines. Tachykinin receptor (TACR1) antagonists are approved for clinical use as
      an antiemetic remedy since 2003. Tachykinin receptor inhibition has recently been
      shown to effectively reduce growth of several tumor types. Here, we report that
      neuroblastoma cell lines express TACR1, and that targeting TACR1 activity
      significantly reduced cell viability and induced apoptosis in neuroblastoma cell
      lines. Gene expression profiling revealed that TACR1 inhibition repressed E2F2
      and induced TP53 signaling. Treating mice harboring established neuroblastoma
      xenograft tumors with Aprepitant also significantly reduced tumor burden. Thus,
      we provide evidence that the targeted inhibition of tachykinin receptor signaling
      shows therapeutic efficacy in preclinical models for high-risk neuroblastoma.

PMID- 27888796
TI  - Altered DNA methylation in neonates born large-for-gestational-age is associated
      with cardiometabolic risk in children.
AB  - BACKGROUND: Infants being born Large-for-gestational-age (LGA) are prone to
      developing cardiometabolic disease. However, the underlying mechanisms remain
      unclear. RESULTS: Clinical investigation showed that children born LGA had
      significantly higher serum level of total cholesterol (TC), low-density
      lipoprotein-cholesterol (LDL-c), and insulin, ratio of TC/high-density
      lipoprotein-cholesterol (HDL-c) compared to children born appropriate for
      gestational age (AGA). Birth weight (BW) was positively correlated to TC, LDL-c,
      and the ratio of TC/HDL in serum. Genome-wide DNA methylation analyzed in
      umbilical cord blood of controls and macrosomia cases. We identified 3459
      methylation variable positions (MVPs) achieving genome-wide significance
      (adjusted P-value < 0.05) with methylation differences of >= 5%. A total of 327
      MVPs were filtered by methylation differences of >= 7% located within an island,
      which mapped to 213 genes. Function analysis using Ingenuity Pathway Analysis
      showed 16 genes enriched in "cardiovascular disease". Four genes included
      contributed to hyperlipidemia. MATERIALS AND METHODS: Fifty-eight children aged 3
      6 years born LGA and 123 subjects born AGA were enrolled. Anthropometric
      parameters and blood pressure (BP) were measured, and metabolic assessment was
      performed in all subjects. Genome-wide DNA methylation in umbilical blood was
      assayed by the 450K BeadChip in six AGA and six macrosomia newborns. CONCLUSIONS:
      Our data indicate that excess birth weight may increase the risk of lipid
      dysfunction in children aged 3-6 years. It might through reprogramming a group of
      genes correlated to cardiovascular disease. The genes identified in this study
      might be potential biomarker for cardiometabolic disease.

PMID- 27888798
TI  - miR-103 inhibits proliferation and sensitizes hemopoietic tumor cells for
      glucocorticoid-induced apoptosis.
AB  - Glucocorticoid (GC) hormones are an important ingredient of leukemia therapy
      since they are potent inducers of lymphoid cell apoptosis. However, the
      development of GC resistance remains an obstacle in GC-based treatment. In the
      present investigation we found that miR-103 is upregulated in GC-sensitive
      leukemia cells treated by the hormone. Transfection of GC resistant cells with
      miR-103 sensitized them to GC induced apoptosis (GCIA), while miR-103 sponging of
      GC sensitive cells rendered them partially resistant. miR-103 reduced the
      expression of cyclin dependent kinase (CDK2) and its cyclin E1 target, thereby
      leading to inhibition of cellular proliferation. miR-103 is encoded within the
      fifth intron of PANK3 gene. We demonstrate that the GC receptor (GR) upregulates
      miR-103 by direct interaction with GC response element (GRE) in the PANK3
      enhancer. Consequently, miR-103 targets the c-Myc activators c-Myb and DVL1,
      thereby reducing c-Myc expression. Since c-Myc is a transcription factor of the
      miR-17~92a poly-cistron, all six miRNAs of the latter are also downregulated. Of
      these, miR-18a and miR-20a are involved in GCIA, as they target GR and BIM,
      respectively. Consequently, GR and BIM expression are elevated, thus advancing
      GCIA. Altogether, this study highlights miR-103 as a useful prognostic biomarker
      and drug for leukemia management in the future.

PMID- 27888797
TI  - Tumorigenicity of Ewing sarcoma is critically dependent on the trithorax proteins
      MLL1 and menin.
AB  - Developmental transcription programs are epigenetically regulated by the
      competing actions of polycomb and trithorax (TrxG) protein complexes, which
      repress and activate genes, respectively. Ewing sarcoma is a developmental tumor
      that is associated with widespread de-regulation of developmental transcription
      programs, including HOX programs. Posterior HOXD genes are abnormally over
      expressed by Ewing sarcoma and HOXD13, in particular, contributes to the
      tumorigenic phenotype. In MLL1 fusion-driven leukemia, aberrant activation of
      HOXA genes is epigenetically mediated by the TrxG complex and HOXA gene
      expression and leukemogenesis are critically dependent on the protein-protein
      interaction between the TrxG proteins MLL1 and menin. Based on these data, we
      investigated whether posterior HOXD gene activation and Ewing sarcoma
      tumorigenicity are similarly mediated by and dependent on MLL1 and/or menin. Our
      findings demonstrate that Ewing sarcomas express high levels of both MLL1 and
      menin and that continued expression of both proteins is required for maintenance
      of tumorigenicity. In addition, exposure of Ewing sarcoma cells to MI-503, an
      inhibitor of the MLL1-menin protein-protein interaction developed for MLL1-fusion
      driven leukemia, leads to loss of tumorigenicity and down-regulated expression of
      the posterior HOXD gene cluster. Together these data demonstrate an essential
      role for MLL1 and menin in mediating tumor maintenance and posterior HOXD gene
      activation in Ewing sarcoma. A critical dependency of these tumors on the MLL1
      menin interaction presents a potentially novel therapeutic target.

PMID- 27888800
TI  - Multipoint Kras oncogene mutations potentially indicate mucinous carcinoma on the
      entire spectrum of mucinous ovarian neoplasms.
AB  - Kras mutation is a common phenomenon in many human neoplasms. We aimed to assess
      the Kras mutational status along the histological continuum from normal ovaries
      to the development of benign, borderline and malignant ovarian mucinous
      neoplasms. We analyzed 41 cases of malignant, 10 cases of borderline, 7 cases of
      benign mucinous ovarian tumors and 7 cases of normal ovarian tissue. The
      prevalence of Kras mutations in the normal ovary was 0.00% (n=0/7), while the
      prevalence in benign, borderline and malignant mucinous neoplasms was 57.14%
      (n=4/7), 90.00% (n=9/10) and 75.61% (n=31/41), respectively. Multiple Kras
      mutations were detected in 6 cases of mucinous carcinoma, including 5 double
      mutations with G13D/V14I (n=1), G12V/G13S (n=1), G12D/G13S (n=3) and one triple
      mutation with A11V/G13N/V14I (n=1). We identified six cases with 3 novel Kras
      mutations not previously described in the COSMIC database, which included A11V
      (n=3) and V14I (n=2) in mucinous carcinomas, and A11T (n=1) in a mucinous
      borderline tumor. In conclusion, Kras mutation appears to be one of the
      imperative events in the ovarian mucinous adenoma-borderline tumor-carcinoma
      sequence, as increased numbers of Kras mutations have been shown to be the
      strongest predictor of unequivocal malignancy in ovarian mucinous neoplasms.

PMID- 27888799
TI  - New bipyridine gold(III) dithiocarbamate-containing complexes exerted a potent
      anticancer activity against cisplatin-resistant cancer cells independent of p53
      status.
AB  - We synthesized, characterized and tested in a panel of cancer cell lines, nine
      new bipyridine gold(III) dithiocarbamate-containing complexes. In vitro studies
      demonstrated that compounds 1, 2, 4, 5, 7 and 8 were the most cytotoxic in
      prostate, breast, ovarian cancer cell lines and in Hodgkin lymphoma cells with
      IC50 values lower than the reference drug cisplatin. The most active compound 1
      was more active than cisplatin in ovarian (A2780cis and 2780CP-16) and breast
      cancer cisplatin-resistant cells. Compound 1 determined an alteration of the
      cellular redox homeostasis leading to increased ROS levels, a decrease in the
      mitochondrial membrane potential, cytochrome-c release from the mitochondria and
      activation of caspases 9 and 3. The ROS scavenger NAC suppressed ROS generation
      and rescued cells from damage. Compound 1 resulted more active in tumor cells
      than in normal human Mesenchymal stromal cells. Gold compounds were active
      independent of p53 status: exerted cytotoxic effects on a panel of non-small cell
      lung cancer cell lines with different p53 status and in the ovarian A2780 model
      where the p53 was knocked out. In conclusion, these promising results strongly
      indicate the need for further preclinical evaluation to test the clinical
      potential of these new gold(III) complexes.

PMID- 27888801
TI  - Common profiles of Notch signaling differentiate disease-free survival in luminal
      type A and triple negative breast cancer.
AB  - Breast cancer (BC) is characterized by high heterogeneity regarding its biology
      and clinical characteristics. The Notch pathway regulates such processes as organ
      modeling and epithelial-to-mesenchymal transition (EMT).The aim of the study was
      to determine the effect of differential expression of Notch members on disease
      free survival (DFS) in luminal type A (lumA) and triple negative (TN) BC.The
      differential expression of 19 Notch members was examined in a TCGA BC cohort. DFS
      analysis was performed using the log-rank test (p<0.05). Biological differences
      between DFS groups were determined with Gene Set Enrichment Analysis (GSEA)
      (tTest, FDR<0.25). Common expression profiles according to Notch signaling were
      examined using ExpressCluster (K-means, mean centered, Euclidean distance
      metric).The overexpression of HES1, LFNG and PSEN1 was found to be favorable for
      DFS in lumA, and lowered expression favorable for DFS in TN.GSEA analysis showed
      that differential Notch signaling is associated with cell cycle, tissue
      architecture and remodeling. Particularly, targets of E2F, early stage S phase
      transcription factor, were upregulated in the lumA unfavorable group and the TN
      favorable group differentiated on a basis of HES1 and PSEN1
      expression.Summarizing, our analysis show significance of Notch signaling in BRCA
      progression through triggering EMT. Moreover, identification of numerous genes
      which overexpression is associated with disease recurrence may serve as a source
      of potential targets for a new anticancer therapy.

PMID- 27888803
TI  - Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for
      diagnosis and prognosis of colorectal cancer.
AB  - Cancer-secreted long non-coding RNAs (lncRNAs) are emerging mediators of cancer
      host cross talk. The aim of our study was to illustrate the clinical significance
      of the lncRNA CRNDE-h in exosomes purified from the serum of patients with
      colorectal cancer (CRC). The study was divided into four parts: (1) The exosome
      isolated methods and lncRNA detected methods which accurately and reproducibly
      measure CRC-related exosomal CRNDE-h in serum were optimized in preliminary pilot
      stage; (2) The stability of exosomal CRNDE-h was evaluated systematically; (3)
      The origin of exosomal CRNDE-h was explorated in vitro and in vivo; (4) The
      diagnostic and prognostic value of exosomal CRNDE-h for CRC were validated in 468
      patients. In pilot study, our results indicated that exosomal CRNDE-h was
      detectable and stable in serum of CRC patients, and derived from tumor cells.
      Then, the increased expression of exosomal CRNDE-h was successfully validated in
      148 CRC patients when compared with colorectal benign disease patients and
      healthy donors. Exosomal CRNDE-h level significantly correlated with CRC regional
      lymph node metastasis (P = 0.019) and distant metastasis (P = 0.003). Moreover,
      at the cut-off value of 0.020 exosomal CRNDE-h level of serum, the area under ROC
      curve distinguishing CRC from colorectal benign disease patients and healthy
      donors was 0.892, with 70.3% sensitivity and 94.4% specificity, which was
      superior to carcinoembryogenic antigen. In addition, high exosomal CRNDE-h level
      has a lower overall survival rates than that for low groups (34.6% vs. 68.2%, P <
      0.001). In conclusion, detection of lncRNA CRNDE-h in exosome shed a light on
      utilizing exosomal CRNDE-h as a noninvasive serum-based tumor marker for
      diagnosis and prognosis of CRC.

PMID- 27888802
TI  - Low dose triptolide reverses chemoresistance in adult acute lymphoblastic
      leukemia cells via reactive oxygen species generation and DNA damage response
      disruption.
AB  - Chemoresistance represents a major challenge for treatment of acute lymphoblastic
      leukemia (ALL). Thus, new drugs to overcome chemoresistance in ALL are urgently
      needed. To this end, we established a cytarabine (araC)-resistant ALL cell line
      (NALM-6/R), which interestingly displayed cross-resistance towards doxorubicin
      (ADM). Here we report that low dose of triptolide (TPL), a natural product used
      for treating inflammatory diseases such as arthritis, could reverse araC and ADM
      resistance and in NALM-6/R cells as well as primary cells from patients with
      relapsed or refractory (R/R) ALL, reflected by inhibition of cell proliferation
      and induction of apoptosis in vitro, and repression of tumor growth in vivo in a
      mouse xenograft model. Mechanistically, these events were associated with
      impaired mitochondrial membrane potential and increased reactive oxygen species
      (ROS) production. Co-treatment with TPL and araC or ADM upregulated pro-apoptotic
      caspase-9 protein, inhibited checkpoint kinase 1 (Chk1) and 2 (Chk2)
      phosphorylation, and induced gammaH2A.X (a DNA damage marker). Notably, the
      combination regimen of TPL and conventional chemotherapeutics also rapidly
      diminished tumor burden in a patient with R/R ALL. Together, these findings
      provide preclinical evidence for repurposing use of TPL in combination with
      chemotherapeutic agents to treat R/R ALL as an alternative salvage regimen.

PMID- 27888804
TI  - Niclosamide and its analogs are potent inhibitors of Wnt/beta-catenin, mTOR and
      STAT3 signaling in ovarian cancer.
AB  - Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer
      mortality worldwide. Platinum-based therapy is the standard first line treatment
      and while most patients initially respond, resistance to chemotherapy usually
      arises. Major signaling pathways frequently upregulated in chemoresistant cells
      and important in the maintenance of cancer stem cells (CSCs) include Wnt/beta
      catenin, mTOR, and STAT3. The major objective of our study was to investigate the
      treatment of ovarian cancer with targeted agents that inhibit these three
      pathways. Here we demonstrate that niclosamide, a salicylamide derivative, and
      two synthetically manufactured niclosamide analogs (analog 11 and 32) caused
      significant inhibition of proliferation of two chemoresistant ovarian cancer cell
      lines (A2780cp20 and SKOV3Trip2), tumorspheres isolated from the ascites of EOC
      patients, and cells from a chemoresistant patient-derived xenograft (PDX). This
      work shows that all three agents significantly decreased the expression of
      proteins in the Wnt/beta-catenin, mTOR and STAT3 pathways and preferentially
      targeted cells that expressed the ovarian CSC surface protein CD133. It also
      illustrates the potential of drug repurposing for chemoresistant EOC and can
      serve as a basis for pathway-oriented in vivo studies.

PMID- 27888805
TI  - Effects of Abies sibirica terpenes on cancer- and aging-associated pathways in
      human cells.
AB  - A large number of terpenoids exhibit potential geroprotector and anti-cancer
      properties. Here, we studied whole transcriptomic effects of Abisil, the extract
      of fir (Abies sibirica) terpenes, on normal and cancer cell lines. We used early
      passaged and senescent none-immortalized fibroblasts as cellular aging models. It
      was revealed that in normal fibroblasts, terpenes induced genes of stress
      response, apoptosis regulation and tissue regeneration. The restoration of the
      expression level of some prolongevity genes after fir extract treatment was shown
      in old cells. In Caco-2 and AsPC-1 cancer cell lines, Abisil induced expression
      of both onco-suppressors (members of GADD45, DUSP, and DDIT gene families), and
      proto-oncogenes (c-Myc, c-Jun, EGR and others). Thus, the study demonstrates the
      potential anti-aging and anti-cancer effects of Abisil on senescent and cancer
      cell lines.

PMID- 27888806
TI  - Decreased DACH1 expression in glomerulopathy is associated with disease
      progression and severity.
AB  - Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated
      protein that regulates cellular differentiation throughout development. Recent
      genome-wide association studies have show that missense mutation in DACH1 leads
      to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate
      glomerular filtration rate (eGFR). We firstly characterized the function of DACH1
      in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in
      human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN)
      patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal
      change disease (MCD) patients. We found that DACH1 expression was decreased in
      the nephropathy group relative to healthy controls. DACH1 staining in the
      glomerulus correlated positively with eGFR (r = 0.41, p < 0.001) but negatively
      with serum creatinine (r = -0.37, p < 0.01). In vitro, DACH1 overexpression in
      human podocytes or HK2 cells decreased expression of cyclin D1, but increased
      expression of p21 and p53, which suggested that DACH1 overexpression in human
      podocytes or HK2 cells increased the G1/S phase or G2/M cell arrest. Together,
      These findings indicate that DACH1 expression is decreased in glomerulopathy
      imply a potential role for DACH1 in the this development of human chornic
      glomerulopathy. These data suggest that DACH1 is a potential a marker of disease
      progression and severity for glomerular diseases.

PMID- 27888807
TI  - Is the positivity of estrogen receptor or progesterone receptor different between
      type 1 and type 2 endometrial cancer?
AB  - Endometrial cancer is a major cancer in women and traditionally divided into type
      1 and type 2. It is well known that type 2 endometrial cancer has a poor
      prognosis. Studies have suggested that estrogen receptor (ER) or progesterone
      receptor (PR) positive are positively associated with endometrial cancer survive.
      However whether the positivity of ER or PR is different between cancer types has
      not been investigated yet. In this retrospective study, the positivity of ER or
      PR was analysed in 1054 women with primary diagnosed endometrial cancer taking
      into account cancer types and menopausal status from the largest university
      teaching women's hospital in China. The positivity of ER or PR (over 90%) was
      significantly higher in type 1 compared to that in type 2 endometrial cancer (71%
      or 64%) in both premenopausal and postmenopausal women. There was no different in
      positivity of ER or PR in type 1 endometrial cancer between premenopausal and
      postmenopausal women. However, in type 2 endometrial cancer, the positivity of ER
      or PR in premenopausal women was significantly higher compared to that in
      postmenopausal women. Our data demonstrate that both ER and PR positivity are
      significantly higher in type 1 endometrial cancer (92%) compared to type 2 (72%
      ER positive, 65% PR positive). Menopausal status is not associated with the
      positivity of ER or PR in type 1 endometrial cancer. Our data may provide some
      novel insights why Asian women have better outcomes of endometrial cancer which
      was reported in the literature.

PMID- 27888808
TI  - Prognostic nutritional index as a prognostic biomarker for survival in digestive
      system carcinomas.
AB  - The prognostic nutritional index (PNI) has been reported to correlate with the
      prognosis in patients with various malignancies. We performed a meta-analysis to
      determine the predictive potential of PNI in digestive system cancers. Twenty
      three studies with a total of 7,384 patients suffering from digestive system
      carcinomas were involved in this meta-analysis. A lower PNI was significantly
      associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95%
      Confidence Interval (CI) 1.62-2.07], the poorer disease-free survival (DFS) (HR
      1.85, 95% CI 1.19-2.89), and the higher rate of post-operative complications (HR
      2.31, 95% CI 1.63-3.28). In conclusion, PNI was allowed to function as an
      efficient indicator for the prognosis of patients with digestive system
      carcinomas.

PMID- 27888809
TI  - Human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis
      via regulation of B lymphocyte maturation.
AB  - Mesenchymal stem cell (MSC) has been applied for the therapy of allergic
      disorders due to its beneficial immunomodulatory abilities. However, the
      underlying mechanisms for therapeutic efficacy are reported to be diverse
      according to the source of cell isolation or the route of administration. We
      sought to investigate the safety and the efficacy of human adipose tissue-derived
      MSCs (hAT-MSCs) in mouse atopic dermatitis (AD) model and to determine the
      distribution of cells after intravenous administration. Murine AD model was
      established by multiple treatment of Dermatophagoides farinae. AD mice were
      intravenously infused with hAT-MSCs and monitored for clinical symptoms. The
      administration of hAT-MSCs reduced the gross and histological signatures of AD,
      as well as serum IgE level. hAT-MSCs were mostly detected in lung and heart of
      mice within 3 days after administration and were hardly detectable at 2 weeks.
      All of mice administered with hAT-MSCs survived until sacrifice and did not
      demonstrate any adverse events. Co-culture experiments revealed that hAT-MSCs
      significantly inhibited the proliferation and the maturation of B lymphocytes via
      cyclooxygenase (COX)-2 signaling. Moreover, mast cell (MC) degranulation was
      suppressed by hAT-MSC. In conclusion, the intravenous infusion of hAT-MSCs can
      alleviate AD through the regulation of B cell function.

PMID- 27888810
TI  - M2 macrophages induce ovarian cancer cell proliferation via a heparin binding
      epidermal growth factor/matrix metalloproteinase 9 intercellular feedback loop.
AB  - In ovarian cancer, a high ratio of anti-inflammatory M2 to pro-inflammatory M1
      macrophages correlates with poor patient prognosis. The mechanisms driving poor
      tumor outcome as a result of the presence of M2 macrophages in the tumor
      microenvironment remain unclear and are challenging to study with current
      techniques. Therefore, in this study we utilized a micro-culture device
      previously developed by our lab to model concentrated paracrine signaling in
      order to address our hypothesis that interactions between M2 macrophages and
      ovarian cancer cells induce tumor cell proliferation. Using the micro-culture
      device, we determined that co-culture with M2-differentiated primary macrophages
      or THP-1 increased OVCA433 proliferation by 10-12%. This effect was eliminated
      with epidermal growth factor receptor (EGFR) or heparin-bound epidermal growth
      factor (HB-EGF) neutralizing antibodies and HBEGF expression in peripheral blood
      mononuclear cells from ovarian cancer patients was 9-fold higher than healthy
      individuals, suggesting a role for HB-EGF in tumor progression. However, addition
      of HB-EGF at levels secreted by macrophages or macrophage-conditioned media did
      not induce proliferation to the same extent, indicating a role for other factors
      in this process. Matrix metalloproteinase-9, MMP-9, which cleaves membrane-bound
      HB-EGF, was elevated in co-culture and its inhibition decreased proliferation.
      Utilizing inhibitors and siRNA against MMP9 in each population, we determined
      that macrophage-secreted MMP-9 released HB-EGF from macrophages, which increased
      MMP9 in OVCA433, resulting in a positive feedback loop to drive HB-EGF release
      and increase proliferation in co-culture. Identification of multi-cellular
      interactions such as this may provide insight into how to most effectively
      control ovarian cancer progression.

PMID- 27888814
TI  - Diaphragmatic Dysfunction after Thoracic Operations.
AB  - The perioperative management of diaphragmatic weakness and phrenic nerve
      dysfunction is complex, due to varied etiologies and clinical presentations. The
      factors leading to diaphragmatic weakness may culminate after the operation with
      transient or persistent respiratory failure. This review discusses diaphragmatic
      disorders and postoperative respiratory failure caused by unilateral or bilateral
      diaphragmatic impairment. The origins of neuromuscular weakness involving the
      diaphragm are diverse, and often lie within the domains of different medical
      specialties, with only a portion of the condition related to surgical
      intervention. Consideration of underlying etiologies for any individual patient
      requires thorough multidisciplinary review. The most important clinical scenarios
      compounding diaphragmatic weakness, including acute myasthenic states, persistent
      neuromuscular blockade, and surgical injury to the phrenic nerve or diaphragm,
      are accessible to attentive surgeons. Awareness of the signs and symptoms of
      undiagnosed weakness, preoperative pursuit of its diagnosis, knowledge of
      surgical alternatives to phrenic nerve resection, and cooperative skills in the
      multidisciplinary management of myasthenia all are crucial to improve patient
      outcomes.

PMID- 27888813
TI  - The Color of a Heart.

PMID- 27888812
TI  - A polysaccharide from Lentinus edodes inhibits human colon cancer cell
      proliferation and suppresses tumor growth in athymic nude mice.
AB  - The antitumor effect of Lentinan is thought rely on the activation of immune
      responses; however, little is known about whether Lentinan also directly attacks
      cancer cells. We therefore investigated the direct antitumor activity of SLNT (a
      water-extracted polysaccharide from Lentinus edodes) and its probable mechanism.
      We showed that SLNT significantly inhibited proliferation of HT-29 colon cancer
      cells and suppressed tumor growth in nude mice. Annxein V-FITC/PI, DAPI, AO/EB
      and H&E staining assays all showed that SLNT induced cell apoptosis both in vitro
      and in vivo. SLNT induced apoptosis by activating Caspase-3 via both intrinsic
      and extrinsic pathways, which presented as the activation of Caspases-9 and -8,
      upregulation of cytochrome c and the Bax/Bcl-2 ratio, downregulation of NF
      kappaB, and overproduction of ROS and TNF-alpha in vitro and in vivo.
      Pretreatment with the caspase-3 inhibitor Ac-DEVD-CHO or antioxidant NAC blocked
      SLNT-induced apoptosis. These findings suggest that SLNT exerts direct antitumor
      effects by inducing cell apoptosis via ROS-mediated intrinsic and TNF-alpha
      mediated extrinsic pathways. SLNT may thus represent a useful candidate for colon
      cancer prevention and treatment.

PMID- 27888815
TI  - Acute diarrhoea induced by rotavirus in children hospitalysed in Provincial
      Hospital for Infectious Diseases in Bydgoszcz in 2014 year
AB  - OBJECTIVE: The aim of the present study was to describe the epidemiology and
      course of rotavirus infection in children hospitalized at the T. Browicz
      Provincial Hospital for Infectious Diseases in Bydgoszcz, Poland in 2014 year.
      INTRODUCTION: Rotavirus infection is responsible for over 2 millions
      hospitalizations per year among children under 5 year old. Rotavirus
      gastroenterocolitis is one of the most common cause of severe dehydration,
      electrolyte disturbances and metabolic acidosis, leading to 400-600 thousand
      deaths per year in children younger than 5 years of age worldwide. MATERIAL AND
      METHODS: Retrospective analysis of medical records of 401 patients hospitalized
      in 2014 year in the Pediatric Infectious Diseases and Hepatology Ward at
      Provincial Hospital for Infectious Diseases in Bydgoszcz, diagnosed with
      rotavirus gastroenterocolitis was taken. RESULTS: Over the study period, 1205
      children with acute gastroenterocolitis were hospitalized. Rotavirus-related
      diarrhea was diagnosed in 401 (33%) cases. The mean age of admitted patients was
      2,75 years and it ranged from 3 weeks to 17 years of age. In the analyzed group,
      56% cases occurred in children 1-3 years of age. The mean length of
      hospitalization was 5,5 days (ranged from 1 to 55 days). Most of children -
      244/401 (61%) were hospitalized for 4-7 days. Presence of additional etiological
      factor was related with prolonged hospitalization - average up to 8,3 days. There
      were reported a hypertransaminazemia (ALAT 47-429 IU/l) in 11% cases.
      Hypoglycemia (<60 mg/dl) was noted in 18/213 (8,45%) children. Metabolic acidosis
      (pH <=7,350) occurred in 35/146 (24%) cases. Hypokalemia (K+ <3,5 mmol/l) were
      reported in 16/154 (10%) patients, and hyponatremia (Na+ <135 mmol/l) in 73/154
      (47,4%) patients. In our studies 19/401 (4,7%) children were vaccinated against
      rotaviruses. CONCLUSIONS: 1. Rotavirus infections are the most common cause of
      diarrheas in children, concerning mainly patients under 4 years of age.2.
      Rotavirus infections can lead to many serious complications - electrolyte
      disturbances, metabolic acidosis and hypoglycemia.3. Among our patients rotavirus
      vaccination insensibly reduced duration of hospitalization.

PMID- 27888816
TI  - Opinions about vaccination among mothers who delivered newborns in two hospitals
      in Krakow and Myslenice
AB  - INTRODUCTION AND OBJECTIVE: Campaigns against vaccinations in Poland have been
      increasingly more frequently observed in recent years, that was the reason of
      bigger number of parents refusing a consent for their children immunization. The
      aim of study was to determine the sources of information which significantly
      influence mothers' opinions about vaccinations. MATERIALS AND METHODS: A survey
      was conducted among 154 randomly selected mothers hospitalized after childbearing
      in two hospitals in Krakow and Myslenice at the end of 2014 and in 2015. The
      research tool was the author's structured questionnaire interview. RESULTS: The
      majority of mothers regarded vaccinations as an efficient method of children
      protection against infectious diseases. Nevertheless, a few percent of women
      admitted that it is not efficient method or had no opinion about it. The mothers'
      confidence was higher for vaccines known for many years compared to new
      formulations - 23.7% did not trust them and 22.4% had no statement on it. The
      most of respondents claimed that the safety of polyvalent vaccines is lower than
      single formulas, and were convinced that children receive too many vaccines.
      About 54.6% of mothers had no opinion and 13.6% admitted that children with
      chronic diseases should not be vaccinated. Depending on the question content from
      3.2% to 54.6% respondents had no opinion about included vaccination issues. The
      pediatricians and family doctors were the main and the most reliable source of
      information about vaccinations. The reliability of doctors was assessed higher by
      citizens of big city compared to women living in rural area (statistically
      significant). Above 50% of mothers used mass media as a source of information
      about vaccination but less than 8% regarded them as reliable. CONCLUSIONS:
      Despite the wide access to different source of information, the newborns' mothers
      too often had the knowledge and opinions about vaccination inconsistent with data
      derived from medical facts. Furthermore, significant group of mothers had no
      opinions about important issues with respect to vaccinations. At the beginning of
      infants life when parents decide of their child immunization, the reliable
      knowledge about that issue should be delivered by GPs because the other sources
      of information are assessed as much less reliable.

PMID- 27888817
TI  - The role of an electronic questionnaires in epidemiologic studies aimed at cancer
      prevention
AB  - The growing number of people diagnosed with cancer is an important issue in
      public health. Evaluation of the population's level of cancer-related knowledge
      is mandatory for planning effective prevention or intervention programs. Until
      recently, traditional methodology, using paper questionnaire or telephone-based
      interviews had dominated previous cross sectional studies related to this issue.
      Currently, the use of new research methods based on information technology
      solutions has been more frequent. Therefore, the aim of this paper is to review
      published data available in the PubMed database towards the identification of
      strengths and weaknesses of crosssectional studies conducted via Internet, a type
      of information technology solution. This review allowed the authors to conclude
      that web-based questionnaire studies could be an effective solution and may
      possibly replace traditionally conducted interviews. Likewise, it evidently
      appears that an online mode is more adequate for querying young people. However,
      there is lack of consensus regarding the cost-effectiveness of the applicationof
      Web technology as a research tool for epidemiological questionnaire-based
      studies. Data security was revealed to be an important aspect of conducting
      Internet-based questionnaire studies. Further efforts are aimed at standardizing
      this type of researches to assess their strengths and weaknesses leading to more
      widespread use.

PMID- 27888811
TI  - The role of p53 in cancer drug resistance and targeted chemotherapy.
AB  - Cancer has long been a grievous disease complicated by innumerable players
      aggravating its cure. Many clinical studies demonstrated the prognostic relevance
      of the tumor suppressor protein p53 for many human tumor types. Overexpression of
      mutated p53 with reduced or abolished function is often connected to resistance
      to standard medications, including cisplatin, alkylating agents (temozolomide),
      anthracyclines, (doxorubicin), antimetabolites (gemcitabine), antiestrogenes
      (tamoxifen) and EGFR-inhibitors (cetuximab). Such mutations in the TP53 gene are
      often accompanied by changes in the conformation of the p53 protein. Small
      molecules that restore the wild-type conformation of p53 and, consequently,
      rebuild its proper function have been identified. These promising agents include
      PRIMA-1, MIRA-1, and several derivatives of the thiosemicarbazone family. In
      addition to mutations in p53 itself, p53 activity may be also be impaired due to
      alterations in p53's regulating proteins such as MDM2. MDM2 functions as primary
      cellular p53 inhibitor and deregulation of the MDM2/p53-balance has serious
      consequences. MDM2 alterations often result in its overexpression and therefore
      promote inhibition of p53 activity. To deal with this problem, a judicious
      approach is to employ MDM2 inhibitors. Several promising MDM2 inhibitors have
      been described such as nutlins, benzodiazepinediones or spiro-oxindoles as well
      as novel compound classes such as xanthone derivatives and trisubstituted
      aminothiophenes. Furthermore, even naturally derived inhibitor compounds such as
      alpha-mangostin, gambogic acid and siladenoserinols have been discovered. In this
      review, we discuss in detail such small molecules that play a pertinent role in
      affecting the p53-MDM2 signaling axis and analyze their potential as cancer
      chemotherapeutics.

PMID- 27888818
TI  - High altitude illness
AB  - High-altitude illness is a result of prolonged high-altitude exposure of
      unacclimatized individuals. The illness is seen in the form of acute mountain
      sickness (AMS) which if not treated leads to potentially life-threatening high
      altitude pulmonary oedema and high-altitude cerebral oedema. Medical problems are
      caused by hypobaric hypoxia stimulating hypoxia-inducible factor (HIF) release.
      As a result, the central nervous system, circulation and respiratory system
      function impairment occurs. The most important factor in AMS treatment is
      acclimatization, withdrawing further ascent and rest or beginning to descent;
      oxygen supplementation, and pharmacological intervention, and, if available, a
      portable hyperbaric chamber. Because of the popularity of high-mountain sports
      and tourism better education of the population at risk is essential.

PMID- 27888820
TI  - The Cochrane collaboration - the role in the evolution of evidence-based medicine
      and development of cooperation in Poland
AB  - Evidence-based medicine (EBM) is an approach to decision making on the basis of
      the reliable and up to date best evidence. EBM is regarded as the gold standard
      all over the world. Cochrane Collaboration is one of the institutions, which
      promote EBM among physicians, policy makers and other health care workers.
      Cochrane Collaboration is international non-profit organization bringing together
      people from all over the world, the aim of which is to create and disseminate
      reliable scientific information. The Cochrane Collaboration develops and
      publishes systematic reviews on medical and diagnostic procedures. The article
      presents the history of the Cochrane Collaboration, the Cochrane Library and the
      first Cochrane Branch in Poland. Cochrane Branch in Poland is hosted by the
      Systematic Reviews Centre created in 2015 within the Faculty of Medicine at the
      Jagiellonian University Medical College in Krakow. The authors presented the
      activities of the Cochrane Collaboration, the scope of activities of Polish
      Branch and briefly principles for the development of Cochrane systematic reviews.

PMID- 27888819
TI  - Lost life years due to premature deaths caused by diseases of the digestive
      system in Poland in 2013
AB  - BACKGROUND: In order to evaluate the health status of a population, besides
      indicators measuring the incidence of diseases and deaths, potential measures are
      becoming more frequently used, ie. measures that take into account life-time
      potential of the individuals in the population. They can particularly by applied
      to analyse the problem of premature mortality, which is measured by lost life
      years. AIM: The aim of the study was to evaluate life years lost due to diseases
      of digestive system in Polish population in 2013. MATERIALS AND METHODS: The
      study was based on a dataset containing 387,312 death certificates of Poles who
      died in 2013, provided by the Central Statistical Office in Poland. Data on
      deaths caused by diseases of digestive system (K00-K93 by ICD-10) were used in
      the study - that were 16,543 records (4.3% of all the deaths). Lost life years
      were assessed with the measures: SEYLL (Standard Expected Years of Life Lost),
      SEYLLp (Standard Expected Years of Life Lost per living person), SEYLLd (Standard
      Expected Years of Life Lost per death). RESULTS: In the analysed year among men
      there were 9,275 deaths caused by diseases of digestive system and in women 7,268
      deaths. SEYLL in the group of men amounted to 102 230.7 and in the group of women
      it was 53,475.5. The number of lost life years calculated per 10 000 male
      inhabitants was 54.9, and for 10,000 females it was 26.9. The highest share in
      lost life years had alcoholic liver disease (SEYLLp for men - 20.87, for women -
      6.1), fibrosis and cirrhosis of the liver (SEYLLp for men- 9.7, for women- 5.6)
      and acute pancreatitis (SEYLLp for men - 5.3, for women - 2.1). CONCLUSIONS: The
      results of the study indicate that diseases of digestive system have an important
      contribution to the loss of life-time potential in Polish population (6.6% of all
      SEYLL in 2013). The dominant role in this class of diseases played alcoholic
      liver disease - K70, fibrosis and cirrhosis of the liver - K74 and acute
      pancreatitis - K85.

PMID- 27888821
TI  - Effect of adenoid hypertrophy and pulmonary function tests in children with mild
      asthma.
AB  - OBJECTIVES: This study aims to assess the effect of adenoid hypertrophy on asthma
      in children with mild asthma. PATIENTS AND METHODS: Between September 2010 and
      September 2012, 63 children (42 males, 21 females; median age 10.5 years; range 6
      to 14 years) admitted to our clinic with asthma complaint were included in this
      study. These children were evaluated for adenoid hypertrophy, symptoms of asthma,
      medical treatment, pulmonary function tests at the beginning of the study and at
      the end of second month. RESULTS: There was no correlation between initial
      pulmonary function tests and adenoid hypertrophy. But we observed significantly
      lower forced vital capacity values in children with prominent adenoid hypertrophy
      (p=0.033). While there was no significant difference in pulmonary function tests
      in terms of inhaled steroid usage (p>0.05), final forced mid-expiratory flow rate
      (FEF25-75) values were statistically higher in patients who were using nasal
      steroids (p=0.015). CONCLUSION: Consequently, significantly higher values of
      FEF25-75 in the group that used nasal steroid suggest that adenoid hypertrophy
      affects the airway obstruction. Moreover, absence of airway obstruction symptoms
      in patients with mild adenoid hypertrophy suggests pulmonary function tests may
      help to decide performing adenoidectomy.

PMID- 27888822
TI  - Long-term results of pillar implant procedure.
AB  - OBJECTIVES: This study aims to investigate the long-term efficiency and
      reliability of the Pillar Implant (PI) procedure. PATIENTS AND METHODS: Between
      January 2008 and January 2010, a total of 27 patients (16 males, 11 females; mean
      age 45.8+/-7.2 years; range 31 to 58 years) who were diagnosed with low
      obstructive sleep apnea syndrome and simple snoring underwent the PI procedure in
      this retrospective, nonrandomized study. The patients were evaluated
      preoperatively with visual analog scale (VAS) scores in terms of snoring,
      dysphagia, mouth dryness, foreign body sensation, and pain at the first month,
      third month, and sixth year intervals. RESULTS: Based on the snoring scale, VAS
      scores were statistically significantly lower in the first month, third month and
      sixth year compared to preoperative scores (p=0.001, p=0.008, p=0.017,
      respectively). There was no pain in any patients beyond the third day. The VAS
      score averages in all evaluations were higher by statistical significance
      relative to the preoperative averages (p=0.018, p=0.027, p=0.025, respectively).
      Mouth dryness was encountered in seven patients. It persisted in seven patients
      at the third month and in five patients at the sixth year interval. The VAS score
      averages were statistically significantly higher in all evaluations compared to
      the preoperative scores (p=0.017, p=0.018, p=0.042, respectively). CONCLUSION:
      Pillar implant is an efficient, reliable method in the long-term; however, it
      should be considered that it could cause complaints such as dysphagia, foreign
      body sensation, and mouth dryness.

PMID- 27888823
TI  - Investigating KRAS/BRAF mutation in oropharyngeal squamous cell carcinomas: a
      preliminary study.
AB  - OBJECTIVES: This study aims to investigate the role of KRAS/BRAF gene mutation in
      the pathogenesis of oropharyngeal squamous cell carcinoma (OSCC). PATIENTS AND
      METHODS: A total of 26 OSCC patients (23 males, 3 females; mean age 60 years;
      range 41 to 77 years) diagnosed between January 2003 and November 2013 were
      included in the study. The methods used in our study were quantitative
      fluorescence polymerase chain reaction for KRAS/BRAF mutation analysis. RESULTS:
      Ten of the tumors were located at the tongue base, 12 in the tonsil and four at
      the floor of mouth. The mean tumor size was 3.8 cm. Six of the tumors were well
      differentiated, 18 were moderately differentiated and two were poorly
      differentiated. All cases were analyzed for KRAS and BRAF gene mutations and none
      of them showed gene mutations. CONCLUSION: We could not find any relation between
      OSCC and KRAS/BRAF gene mutations in our short case file. The role of mutations
      should be analyzed in larger series in OSCC to predict new targeted therapy
      modalities.

PMID- 27888825
TI  - [Publication rates of audiology master and doctoral theses in peer-reviewed
      journals].
AB  - OBJECTIVES: Theses are the prime indicators of the scientific productivity of a
      country and one of the main and strongest resources for the emergence of
      scientific articles. This study aims to examine, by using the survey method, how
      many of the audiology master and/or doctoral theses in Turkey were turned into a
      scientific work. PATIENTS AND METHODS: Individuals who received a master's degree
      in audiology were surveyed whether their theses had been reviewed as a paper or
      publication. RESULTS: Forty-five of the 230 audiology specialists and 22
      audiologists with a doctorate degree working in Turkey participated in the study
      by answering the survey questions. In general, while 45.4% of master theses were
      presented orally or as a poster presentation in a national convention, 20.4% were
      presented orally or as a poster presentation in an international convention.
      While 18.1% of theses were published as an article in a national journal, 15.9%
      were published as an article in an international SCI or SCI-E journal. The
      distribution of the doctoral theses is 26.6%, 33.3%, 13.3% and 26.6%,
      respectively. CONCLUSION: We found the rate of theses in audiology turning into a
      scientific article to be below the desired level, as in other fields. The reasons
      for this should be emphasized and efforts should be made to raise these rates to
      the desired level.

PMID- 27888824
TI  - Clinico-radiological parameters predicting early diagnosis of foreign body
      aspiration in children.
AB  - OBJECTIVES: This study aims to investigate clinical and radiological findings to
      make early diagnosis of foreign body (FB) aspiration in children. PATIENTS AND
      METHODS: This prospective study was conducted on 45 children younger than 12
      years with a clinical diagnosis of FB aspiration undergone rigid bronchoscopy
      between September 2010 and May 2014. The results of 37 children (22 males, 15
      females; mean age 2.6 years; range 1 to 12 years) with positive for FB on
      bronchoscopy were analyzed. RESULTS: Penetration syndrome (sudden onset coughing,
      choking and gagging) (89.2%) and decreased breath sounds (86.5%) were the most
      common clinical features. Cough, respiratory difficulty and fever were present in
      83.8%, 78.4% and 27% respectively. Tachypnea, tachycardia, chest retractions,
      decreased chest movements and wheeze were present in 83.3%, 83.3%, 83.3%, 51.4%
      and 43.2% respectively. Unilateral hyperinflation (64.9%), mediastinal shift
      (45.9%), and collapse (21.6%) were common radiological signs on chest radiography
      and in 13.5% patients the chest X-rays were normal. Sites of FB lodgements were
      larynx, trachea, right main bronchus, left main bronchus and bilateral bronchi in
      10.8%, 10.8%, 35.1%, 37.8 and 5.5% respectively. Food related FBs were present in
      30 cases (peanut 54.1%) and inorganic FBs were present in seven cases.
      CONCLUSION: Penetration syndrome, localized decreased breath sounds, unilateral
      hyperinflation and/or mediastinal shift on radiology are predictors for early
      diagnosis of FB aspiration.

PMID- 27888826
TI  - Clinical significance of Ki-67, c-erbB-2 and E-cadherin expressions in open
      partial laryngectomy patients.
AB  - OBJECTIVES: This study aims to analyze the correlation between biomarkers and
      risks of cervical lymph node invasion, recurrence, distant metastasis and
      survival regarding the clinicopathological variables in laryngeal cancers.
      PATIENTS AND METHODS: Forty-one patients with laryngeal cancers were examined
      retrospectively. The correlations evaluated between E-cadherin, Ki-67, c-erbB-2
      expressions, tumor site, differentiation, the risk of cervical lymph node
      metastasis, perineural, perivascular, pericapsular invasion and recurrence as
      well as survival time. RESULTS: There was significant correlation between T-grade
      and the survival rates, and between pericapsular invasion and the lowest survival
      rates. There was no significant correlation between E-cadherin, Ki-67, c-erbB-2
      expressions and clinicopathological variables of tumor. Positive correlation
      between strong stain of E-cadherin and Ki-67 proliferation index was determined.
      CONCLUSION: These markers are not reliable prognostic and predictive factors for
      laryngeal cancers. E-cadherin expression was protected in well-differentiated and
      less invasive cancers, which maintain their cell-cell adhesions whereas it was
      reduced in undifferentiated cancers. Positive correlation between E-cadherin and
      Ki-67 proliferation shows that histopathological differentiation of laryngeal
      cancers is maintained in spite of the high proliferation index.

PMID- 27888827
TI  - Excision of recurrent synovial sarcoma of the infratemporal fossa.
AB  - Synovial sarcoma is a soft tissue sarcoma especially encountered in the lower
      extremities. The infratemporal fossa is quite a rare location. Since it is a
      closed location, combined approaches and multidisciplinary planning always need
      to be considered. This case emphasizes the high-grade character of synovial
      sarcoma, which causes it to recur often. The difficulty of clear surgical margins
      in the infratemporal fossa adds to synovial sarcoma a second challenging issue.
      Therefore, the need of complementary therapy is essential. In this case, we
      applied postoperative radiotherapy and we did not observe any sign of local,
      regional or distant metastasis in the one-year follow-up. In this article, we
      present a 68-year-old male patient together with totally excised synovial sarcoma
      in the infratemporal fossa by mandibular swing and transzygomatic technique
      information on the manifestation, imaging, histopathological features and
      postoperative complications of previous infratemporal fossa synovial sarcomas.

PMID- 27888828
TI  - Nasal chondromesenchymal hamartoma: a rare nasal benign tumor.
AB  - Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal benign tumor, which
      arises from the nasal cavity or paranasal sinuses. In this article, we present a
      five-year-old male patient with rhabdomyosarcoma unity in remission that emerged
      with nasal obstruction. Synchronous diagnosis of pediatric tumors such as
      pleuropulmonary blastoma in the literature is a remarkable finding. We found a
      mass within the left nasal cavity originating from superior portion of nasal
      septum, extending to the olfactory cleft and resected all tumor via endoscopic
      surgical approach. Histopathological diagnosis revealed that NCMH contained
      cartilaginous and mesenchymal components. In conclusion, NCMH is a rare
      surgically treated benign tumor that can be synchronously diagnosed with
      pleuropulmonary blastoma and should be kept in mind for differential diagnosis of
      unilateral pediatric nasal mass.

PMID- 27888829
TI  - Treatment of seborrheic keratosis in bilateral external auditory canal using
      fiber CO2 laser.
AB  - In this article, we report a 33-year-old female patient with lesions of bilateral
      external auditory canals who was treated using fiber CO2 laser without
      canaloplasty. Histopathological examination confirmed the diagnosis of irritated
      type seborrheic keratosis, which is rare in external auditory canal. Twelve
      months after the treatment, the patient showed no signs of recurrence.

PMID- 27888830
TI  - [Giant retropharyngeal abscess in pediatric patient: case report].
AB  - A two-year-old girl patient, who presented to another center with three months of
      sore throat and one month of neck swelling with pain, was initiated
      antibiotherapy but no healing was achieved. Afterwards, the patient was directed
      to our clinic and an abscess was detected in magnetic resonance imaging extending
      in both lateral spaces of the neck. The patient was performed surgical drainage
      urgently. The wound was dressed with rifampicin and the patient was started
      parenteral antibiotherapy. A dramatic recovery was observed and no complication
      occurred in the patient.

PMID- 27888831
TI  - [Extranasal glioma surgery in a newborn: a case report].
AB  - Nasal gliomas are rarely seen, congenital, benign and nonhereditary lesions.
      These are not true tumors that occur due to extradural malposition of ectopic
      glial tissue during embryologic development. These are generally diagnosed during
      childbirth and may have an intracranial extension with fibrous stalk. Treatment
      of these masses that cause nasal obstruction and cosmetic deformity according to
      location, is total excision. In this case report, we present an extranasal glioma
      case whose surgery was done when she was 11 days old. Nasal gliomas are
      congenital midline lesions in the newborn period and it is necessary to be
      careful in differential diagnosis and during surgery due to possible intracranial
      extension.

PMID- 27888832
TI  - [Foreign body aspirations].

PMID- 27888833
TI  - Interaction of rat alveolar macrophages with dental composite dust.
AB  - BACKGROUND: Dental composites have become the standard filling material to
      restore teeth, but during the placement of these restorations, high amounts of
      respirable composite dust (<5 MUm) including many nano-sized particles may be
      released in the breathing zone of the patient and dental operator. Here we tested
      the respirable fraction of several composite particles for their cytotoxic effect
      using an alveolar macrophage model system. METHODS: Composite dust was generated
      following a clinical protocol, and the dust particles were collected under
      sterile circumstances. Dust was dispersed in fluid, and 5-MUm-filtered to enrich
      the respirable fractions. Quartz DQ12 and corundum were used as positive and
      negative control, respectively. Four concentrations (22.5 MUg/ml, 45 MUg/ml, 90
      MUg/ml and 180 MUg/ml) were applied to NR8383 alveolar macrophages. Light and
      electron microscopy were used for subcellular localization of particles. Culture
      supernatants were tested for release of lactate dehydrogenase, glucuronidase, TNF
      alpha, and H2O2. RESULTS: Characterization of the suspended particles revealed
      numerous nano-sized particles but also many high volume particles, most of which
      could be removed by filtering. Even at the highest concentration (180 MUg/ml),
      cells completely cleared settled particles from the bottom of the culture vessel.
      Accordingly, a mixture of nano- and micron-scaled particles was observed inside
      cells where they were confined to phagolysosomes. The filtered particle fractions
      elicited largely uniform dose-dependent responses, which were elevated compared
      to the control only at the highest concentration, which equaled a mean cellular
      dose of 120 pg/cell. A low inflammatory potential was identified due to dose
      dependent release of H2O2 and TNF-alpha. However, compared to the positive
      control, the released levels of H2O2 and TNF-alpha were still moderate, but their
      release profiles depended on the type of composite. CONCLUSIONS: Alveolar
      macrophages are able to phagocytize respirable composite dust particle inclusive
      nanoparticles. Since NR8383 cells tolerate a comparatively high cell burden (60
      pg/cell) of each of the five materials with minimal signs of cytotoxicity or
      inflammation, the toxic potential of respirable composite dust seems to be low.
      These results are reassuring for dental personnel, but more research is needed to
      characterize the actual exposure and uptake especially of the pure nano fraction.

PMID- 27888834
TI  - Exploring the impact of word-of-mouth about Physicians' service quality on
      patient choice based on online health communities.
AB  - BACKGROUND: Health care service is a high-credence service and patients may face
      difficulties ascertaining service quality in order to make choices about their
      available treatment options. Online health communities (OHCs) provide a
      convenient channel for patients to search for physicians' information, such as
      Word-of-Mouth (WOM), particularly on physicians' service quality evaluated by
      other patients. Existing studies from other service domains have proved that WOM
      impacts consumer choice. However, how patients make a choice based on physicians'
      WOM has not been studied, particularly with reference to different patient
      characteristics and by using real data. METHODS: One thousand eight hundred fifty
      three physicians' real data were collected from a Chinese online health
      community. The data were analyzed using ordinary least squares (OLS) method.
      RESULTS: The study found that functional quality negatively moderated the
      relationship between technical quality and patient choice, and disease risk
      moderated the relationship between physicians' service quality and patient
      choice. CONCLUSIONS: Our study recommends that hospital managers need to consider
      the roles of both technical quality and functional quality seriously. Physicians
      should improve their medical skills and bedside manners based on the severity and
      type of disease to provide better service.

PMID- 27888837
TI  - Changes in the profile of Australians in 77 residential aged care facilities
      across New South Wales and the Australian Capital Territory.
AB  - Objective Government expenditure on and the number of aged care facilities in
      Australia have increased consistently since 1995. As a result, a range of aged
      care policy changes have been implemented. Data on demographics and utilisation
      are important in determining the effects of policy on residential aged care
      services. Yet, there are surprisingly few statistical summaries in the peer
      reviewed literature on the profile of Australian aged care residents or trends in
      service utilisation. Therefore, the aim of the present study was to characterise
      the demographic profile and utilisation of a large cohort of residential aged
      care residents, including trends over a 3-year period. Methods We collected 3
      years of data (2011-14) from 77 residential aged care facilities and assessed
      trends and differences across five demographic and three service utilisation
      variables. Results The median age at admission over the 3-year period remained
      constant at 86 years. There were statistically significant decreases in
      separations to home (z=2.62, P=0.009) and a 1.35% increase in low care
      admissions. Widowed females made up the majority (44.75%) of permanent residents,
      were the oldest and had the longest lengths of stay. One-third of permanent
      residents had resided in aged care for 3 years or longer. Approximately 30% of
      residents were not born in Australia. Aboriginal residents made up less than 1%
      of the studied population, were younger and had shorter stays than non-Aboriginal
      residents. Conclusion The analyses revealed a clear demographic profile and
      consistent pattern of utilisation of aged care facilities. There have been
      several changes in aged care policy over the decades. The analyses outlined
      herein illustrate how community, health services and public health data can be
      used to inform policy, monitor progress and assess whether intended policy has
      had the desired effects on aged care services. What is known about the topic?
      Characterisation of permanent residents and their utilisation of residential aged
      care facilities is poorly described in the peer-reviewed literature. Further,
      publicly available government reports are incomplete or characterised using
      incomplete methods. What does this paper add? The analyses in the present study
      revealed a clear demographic profile and consistent pattern of utilisation of
      aged care facilities. The most significant finding of the study is that one-third
      of permanent residents had resided in an aged care facility for >=3 years. These
      findings add to the overall picture of residential aged care utilisation in
      Australia. What are the implications for practitioners? The analyses outlined
      herein illustrate how community, health services and public health data can be
      utilised to inform policy, monitor progress and assess whether or not intended
      policy has had the desired effects on aged care services.

PMID- 27888836
TI  - Limited predictability of maximal muscular pressure using the difference between
      peak airway pressure and positive end-expiratory pressure during proportional
      assist ventilation (PAV).
AB  - BACKGROUND: If the proportional assist ventilation (PAV) level is known, muscular
      effort can be estimated from the difference between peak airway pressure and
      positive end-expiratory pressure (PEEP) (DeltaP) during PAV. We conjectured that
      deducing muscle pressure from DeltaP may be an interesting method to set PAV, and
      tested this hypothesis using the oesophageal pressure time product calculation.
      METHODS: Eleven mechanically ventilated patients with oesophageal pressure
      monitoring under PAV were enrolled. Patients were randomly assigned to seven
      assist levels (20-80%, PAV20 means 20% PAV gain) for 15 min. Maximal muscular
      pressure calculated from oesophageal pressure (Pmus, oes) and from DeltaP (Pmus,
      aw) and inspiratory pressure time product derived from oesophageal pressure
      (PTPoes) and from DeltaP (PTPaw) were determined from the last minute of each
      level. Pmus, oes and PTPoes with consideration of PEEPi were expressed as Pmus,
      oes, PEEPi and PTPoes, PEEPi, respectively. Pressure time product was expressed
      as per minute (PTPoes, PTPoes, PEEPi, PTPaw) and per breath (PTPoes, br, PTPoes,
      PEEPi, br, PTPaw, br). RESULTS: PAV significantly reduced the breathing effort of
      patients with increasing PAV gain (PTPoes 214.3 +/- 80.0 at PAV20 vs. 83.7 +/-
      49.3 cmH2O*s/min at PAV80, PTPoes, PEEPi 277.3 +/- 96.4 at PAV20 vs. 121.4 +/-
      71.6 cmH2O*s/min at PAV80, p < 0.0001). Pmus, aw overestimates Pmus, oes for low
      gain PAV and underestimates Pmus, oes for moderate-gain to high-gain PAV. An
      optimal Pmus, aw could be achieved in 91% of cases with PAV60. When the PAV gain
      was adjusted to Pmus, aw of 5-10 cmH2O, there was a 93% probability of PTPoes
      <224 cmH2O*s/min and 88% probability of PTPoes, PEEPi < 255 cmH2O*s/min.
      CONCLUSION: Deducing maximal muscular pressure from DeltaP during PAV has limited
      accuracy. The extrapolated pressure time product from DeltaP is usually less than
      the pressure time product calculated from oesophageal pressure tracing. However,
      when the PAV gain was adjusted to Pmus, aw of 5-10 cmH2O, there was a 90%
      probability of PTPoes and PTPoes, PEEPi within acceptable ranges. This
      information should be considered when applying DeltaP to set PAV under various
      gains.

PMID- 27888838
TI  - Five decades of homonuclear dipolar decoupling in solid-state NMR: Status and
      outlook.
AB  - It has been slightly more than fifty years since the first homonuclear spin
      decoupling scheme, Lee-Goldburg decoupling, was proposed for removing homonuclear
      dipolar interactions in solid-state nuclear magnetic resonance. A family of such
      schemes has made observation of high-resolution NMR spectra of abundant spins
      possible in various applications in solid state. This review outlines the
      strategies used in this field and the future prospects of homonuclear spin
      decoupling in solid-state NMR.

PMID- 27888835
TI  - The association between benzodiazepine use and sleep quality in residential aged
      care facilities: a cross-sectional study.
AB  - BACKGROUND: Benzodiazepines are commonly prescribed in residential aged care
      facilities (RACFs) for their sedative and anxiolytic effects. The objective of
      this study was to investigate the association between benzodiazepine use and
      sleep quality in residents of RACFs. METHODS: A cross-sectional study involving
      383 participants was conducted in six Australian RACFs. Night-time sleep quality,
      day-time drowsiness and day-time napping behavior were assessed using a validated
      questionnaire. Logistic regression was used to compute adjusted odds ratios
      (AORs) and 95% confidence intervals (CIs) for the association between
      benzodiazepine use and sleep quality. Covariates included pain, dementia
      severity, depression, insomnia and other sedative use. RESULTS: Of the 383
      residents (mean age 87.5 years, 77.5% female), 96(25.1%) used a benzodiazepine on
      a regular basis. Residents who used long-acting benzodiazepines on a regular
      basis had higher night-time sleep quality than non-users (AOR = 4.00, 95%CI 1.06 
      15.15). Residents who used short-acting benzodiazepines on a PRN only basis had
      longer daytime napping times than non-users (AOR = 1.77, 95%CI 1.01 - 3.08). No
      benzodiazepine category was associated with day-time drowsiness. CONCLUSIONS: The
      association between benzodiazepine use and sleep quality is dependent on the half
      life and prescribing pattern of the benzodiazepine. Short-acting PRN
      benzodiazepines were associated with lower night time sleep quality and longer
      day-time napping compared to long-acting regular benzodiazepines. Longitudinal
      studies are needed to determine whether these findings reflect channeling of
      short-acting agents to residents at higher risk of sleep disorders.

PMID- 27888839
TI  - Detection of intermolecular NOE interactions in large protein complexes.
AB  - Intermolecular NOE interactions are invaluable for structure determination of
      biomolecular complexes by NMR and they represent the "gold-standard" amongst NMR
      measurements for characterizing interfaces. These NOEs constitute only a small
      fraction of the observed NOEs in a complex and are usually weaker than many of
      the intramolecular NOEs. A number of methods have been developed to remove the
      intramolecular NOEs that interfere with the identification of intermolecular
      NOEs. NMR experiments used to observe intermolecular NOE interactions in large
      protein complexes must cope with the short T2 relaxation time of the protons and
      heteronuclei in these complexes because they result in severe losses in
      sensitivity. The isotope-edited/isotope-filtered experiment is a powerful method
      for extraction of intermolecular NOEs in biomolecular complexes. Its application
      to large protein complexes is limited because of severe losses in signal-to-noise
      ratio caused by delays in the pulse sequence necessary for the multiple
      magnetization transfer steps between protons and heteronuclei. Isotope
      edited/isotope-edited experiments, in which one protein is usually labeled with
      13C and the other is labeled with 15N, reduce possible artifacts in the filtering
      experiments and improve somewhat the sensitivity of these experiments.
      Sensitivity can also be improved by deuteration of the components of the complex
      in order to replace either or both of the filtering or editing steps. Asymmetric
      deuteration, where aromatic residues in one protein and non-aromatic amino acids
      in the other are reverse protonated, can eliminate the editing and the filtering
      steps altogether, thus maintaining high sensitivity even for large proteins
      complexes. Difference spectroscopy and the use of 2D NOESY experiments without
      using editing or filtering steps can significantly increase the signal-to-noise
      ratio in experiments aimed at observing intermolecular NOEs. The measurement of
      NOESY spectra of three different preparations of a heterodimeric complex under
      investigation in which one or neither of the components is uniformly deuterated,
      and calculation of a double difference spectrum provides information on all
      intermolecular NOEs of non-exchangeable protons. Recent studies indicate that
      many protein-protein interactions are actually between a protein and a linear
      peptide recognition motif of the second protein, and determinants represented by
      linear peptides contribute significantly to the binding energy. NMR is a very
      versatile method to study peptide-protein interactions over a wide range of
      binding affinities and binding kinetics. Protein-peptide interactions in
      complexes exhibiting tight binding can be studied using single and/or multiple
      deuteration of the peptide residues and measuring a difference NOESY spectrum.
      This difference spectrum will show exclusively intra- and intermolecular
      interactions of the peptide protons that were deuterated. Transferred nuclear
      Overhauser spectroscopy (TRNOE) extends NMR to determine interactions within and
      between a weakly-bound rapidly-exchanging peptide and its protein target. TRNOE,
      together with asymmetric deuteration, is applicable to complexes up to ~100KDa
      and is highly sensitive, taking advantage of the long average T2 of the peptide
      protons. Among the methods described in this review, TRNOE has the best potential
      to determine intermolecular NOEs for the upper molecular weight limit of proteins
      that can be studied in detail by NMR.

PMID- 27888840
TI  - NMR solution structure determination of large RNA-protein complexes.
AB  - Structure determination of RNA-protein complexes is essential for our
      understanding of the multiple layers of RNA-mediated posttranscriptional
      regulation of gene expression. Over the past 20years, NMR spectroscopy became a
      key tool for structural studies of RNA-protein interactions. Here, we review the
      progress being made in NMR structure determination of large ribonucleoprotein
      assemblies. We discuss approaches for the design of RNA-protein complexes for NMR
      structural studies, established and emerging isotope and segmental labeling
      schemes suitable for large RNPs and how to gain distance restraints from NOEs,
      PREs and EPR and orientational information from RDCs and SAXS/SANS in such
      systems. The new combination of NMR measurements with MD simulations and its
      potential will also be discussed. Application and combination of these various
      methods for structure determination of large RNPs will be illustrated with three
      large RNA-protein complexes (>40kDa) and other interesting complexes determined
      in the past six and a half years.

PMID- 27888841
TI  - NMR in drug discovery: A practical guide to identification and validation of
      ligands interacting with biological macromolecules.
AB  - Protein-ligand interactions are at the heart of drug discovery research. NMR
      spectroscopy is an excellent technology to identify and validate protein-ligand
      interactions. A plethora of NMR methods are available which are powerful, robust
      and information-rich, but also have pitfalls and limitations. In this review, we
      will focus on how to choose between different experiments, and assess their
      strengths and liabilities. We introduce the concept of the validation cross,
      which helps to categorize experiments according to their information content and
      to simplify the choice of the right experiment in order to address a specific
      question. Additionally, we will provide the framework for drawing correct
      conclusions from experimental results in order to accurately evaluate such
      interactions. Out of scope for this review are methods for subsequent
      characterization of the interaction such as quantitative KD determination,
      binding mode analysis, or structure determination.

PMID- 27888842
TI  - Technical Considerations: Best Practices for MR Imaging of the Foot and Ankle.
AB  - There are many challenges involved in obtaining diagnostic MR images of the foot
      and ankle. The complex anatomy and morphology, with curved and angular structures
      localized to the periphery of the body, make for an inherent challenge, let alone
      if an added level of complexity, such as orthopedic instrumentation, is added.
      This review outlines the technical considerations best designed to produce
      diagnostic images of the foot and ankle, with an emphasis on the postoperative
      state, including imaging in the presence of metal.

PMID- 27888844
TI  - MR Imaging of the Plantar Plate: Normal Anatomy, Turf Toe, and Other Injuries.
AB  - The metatarsophalangeal (MTP) joint complex is a weight-bearing structure
      important to the biomechanics of the standing position, walking, shoe wearing,
      and sport participation. Acute dorsiflexion injury of the first MTP joint, "turf
      toe," is common among American football and soccer players. The first and lesser
      MTP joint complexes can be affected by degenerative or inflammatory arthritis,
      infarct, and infection. These conditions can lead to plantar plate disruption.
      Imaging studies help physicians to properly diagnose and treat this condition.
      This article reviews the anatomy, diagnostic imaging, and clinical management of
      injury and pathology of the first and lesser MTP joint complexes.

PMID- 27888843
TI  - Normal Variants: Accessory Muscles About the Ankle.
AB  - Accessory muscles around the ankle are commonly encountered as incidental
      findings on cross-sectional imaging. Mostly asymptomatic, accessory muscles
      sometimes mimic mass lesions. They have been implicated as the cause of tarsal
      tunnel syndrome, impingement of surrounding structures, and chronic pain.
      Distinguishing these muscles can be challenging, because some travel along a
      similar path. This article describes these accessory muscles in detail, including
      their relationships to the aponeurosis of the lower leg. An imaging algorithm is
      proposed to aid in identification of these muscles, providing a valuable tool in
      diagnostic accuracy and subsequent patient management.

PMID- 27888845
TI  - MR Imaging of Impingement and Entrapment Syndromes of the Foot and Ankle.
AB  - Impingement is a clinical syndrome of chronic pain and restricted range of
      movement caused by compression of abnormal bone or soft tissue within the ankle
      joint. It usually occurs following a sprain injury or repetitive microtrauma
      causing haemorrhage, synovial hyperplasia, and abnormal soft tissue interposition
      within the joint. MR imaging is particularly valuable in being able to detect not
      only the soft tissue and osseous abnormalities involved in these syndromes, but
      also a wide variety of other potential causes of ankle pain and instability that
      also may need to be addressed clinically.

PMID- 27888846
TI  - MR Imaging of Common Soft Tissue Masses in the Foot and Ankle.
AB  - Soft tissue masses may be encountered in the foot and ankle and may represent
      true neoplasms, malignant or benign, or other, nonneoplastic entities that mimic
      musculoskeletal tumors. This article reviews common soft tissue masses
      encountered in the foot or ankle, highlights their MR imaging appearance, and
      outlines common pitfalls. Technical considerations for imaging soft tissue masses
      in the foot and ankle are discussed. On MR imaging, T1-weighted and T2-weighted
      signal intensity, contrast enhancement characteristics, and lesion location,
      together with patient demographics, history and physical examination, and
      findings on radiographs, can be useful in characterizing masses in the foot and
      ankle.

PMID- 27888847
TI  - MR Imaging of the Diabetic Foot.
AB  - Abnormalities of the peripheral nervous, vascular, and immune systems contribute
      to the development of numerous foot and ankle pathologies in the diabetic
      population. Although radiographs remain the most practical first-line imaging
      tool, magnetic resonance (MR) is the tertiary imaging modality of choice,
      allowing for optimal assessment of bone and soft tissue abnormalities. MR allows
      for the accurate distinction between osteomyelitis/septic arthritis and
      neuropathic osteoarthropathy. Furthermore, it provides an excellent presurgical
      anatomic road map of involved tissues and devitalized skin to ensure successful
      limited amputations when required. Signal abnormality in the postoperative foot
      aids in the diagnosis of recurrent infection.

PMID- 27888848
TI  - Postoperative Foot and Ankle MR Imaging.
AB  - MR imaging has an important role in the evaluation of the postoperative foot and
      ankle. In this article, a variety of operative techniques and postoperative
      findings in the foot and ankle are described, including tendon and ligament
      reconstruction, as well as the treatment of tarsal coalition and Morton neuroma.
      The role of MR imaging in the assessment of complications of foot and ankle
      surgery is also detailed.

PMID- 27888850
TI  - MR Imaging of the Pediatric Foot and Ankle: What Does Normal Look Like?
AB  - MR imaging is ideally suited for characterization of the soft tissue,
      cartilaginous, and osseous structures of the pediatric ankle. An understanding of
      the normal MR imaging appearance associated with the dynamic skeletal maturation
      process will prevent overdiagnosis and unnecessary treatment. In this article, we
      review the normal MR imaging appearance of the growing ankle as well as several
      disease processes unique to the pediatric population.

PMID- 27888851
TI  - Aftermath of Ankle Inversion Injuries: Spectrum of MR Imaging Findings.
AB  - Acute and chronic ankle inversion injuries are a common source of pain and a
      diagnostic challenge. Several studies have shown a variety of injury patterns
      after inversion injury both in acute and chronic settings. Although traditional
      assessment with clinical examination and radiographs is generally accepted for
      inversion injuries, MR imaging is a useful tool to detect occult injuries and in
      patients with chronic symptoms. This article examines a range of MR imaging
      findings that may be present in patients with lateral ankle pain following an
      acute or chronic inversion injury.

PMID- 27888852
TI  - Medial-sided Ankle Pain: Deltoid Ligament and Beyond.
AB  - Abnormalities of the medial ligaments and posterior tibial tendon can occur
      because of acute injury or chronic instability or malalignment. Medial ankle
      injuries may occur because of pronation or supination-external rotation injuries.
      Deltoid ligament injuries have a significant impact on lateral ankle instability
      but can be overlooked in patients with lateral ligament injuries. Posterior
      tibial tendon dysfunction is usually associated with spring ligament or flexor
      retinaculum injury. Tarsal tunnel syndrome, accessory flexor muscles, and
      subtalar coalition should be considered as well as ligament and tendon tears in
      differential diagnosis of chronic medial ankle pain.

PMID- 27888849
TI  - New Techniques in MR Imaging of the Ankle and Foot.
AB  - Foot and ankle disorders are common in everyday clinical practice. MR imaging is
      frequently required for diagnosis given the variety and complexity of foot and
      ankle anatomy. Although conventional MR imaging plays a significant role in
      diagnosis, contemporary management increasingly relies on advanced imaging for
      monitoring therapeutic response. There is an expanding need for identification of
      biomarkers for musculoskeletal tissues. Advanced imaging techniques capable of
      imaging these tissue substrates will be increasingly used in routine clinical
      practice. Radiologists should therefore become familiar with these innovative MR
      techniques. Many such techniques are already widely used in other organ systems.

PMID- 27888853
TI  - MR Imaging Findings in Heel Pain.
AB  - Heel pain is common and due to a variety of osseous and soft tissue disorders.
      Causes of heel pain can be classified by the anatomic structure in which they
      arise and include disorders of the (1) Achilles tendon, (2) plantar fascia, (3)
      calcaneus, (4) bursae, (5) nerves in the hindfoot, (6) and heel pad. Although
      careful history taking and physical examination are important, imaging plays a
      vital role in the diagnosis and management of heel pain. MR imaging is the best
      imaging test to assess pain in the heel. This review discusses the common causes
      of heel pain, focusing on MR imaging appearances.

PMID- 27888854
TI  - MR Imaging of the Midfoot Including Chopart and Lisfranc Joint Complexes.
AB  - Following a brief description of the normal anatomy and biomechanics of the
      midfoot, this article focuses on MR imaging features of common osseous, tendon,
      and ligament abnormalities that affect the midfoot. Discussion of the anatomy and
      pathology affecting the Chopart and Lisfranc joint complexes, both of which play
      important roles in linking the midfoot to the hindfoot and the forefoot
      respectively, is also included.

PMID- 27888855
TI  - Foreword.

PMID- 27888856
TI  - Preface.

PMID- 27888857
TI  - ?

PMID- 27888858
TI  - Novel findings in the management of acute pancreatitis.
AB  - Acute pancreatitis (AP) is a potentially serious disease whose incidence is on
      the increase. Pancreas divisum does not meet the required criteria to be
      considered an aetiological factor. Sphincter of Oddi dysfunction may be another
      cause of idiopathic AP. Less invasive methods cannot replace Sphincter of Oddi
      manometry in diagnosis. Almost half of patients with systemic inflammatory
      response syndrome develop organ failure, but the mechanisms involved are not
      completely understood. Obesity is a risk factor for severity in AP; the cause
      could be the presence of free unsaturated fatty acids, which have pro
      inflammatory activity. Prognosis is better in patients with isolated extra
      pancreatic necrosis than in those with parenchymal necrosis or with both. The
      mortality rate among those with infected pancreatic necrosis is 15-20%. The
      "moderately severe" group is widely heterogeneous and this category may require
      redefinition. Laparoscopic treatment of pseudocysts is an alternative to
      endoscopic drainage and could be the first-line option in patients requiring
      cholecystectomy. The use of lumen-apposing metal stents to treat pancreatic
      necrosis is cost-effective. Quality of life in some patients following an attack
      of AP is significantly impaired even at 1 year. Aggressive fluid therapy is not
      superior to standard fluid therapy in preventing post-ERCP AP. The role of
      statins in AP prevention is still unclear. Aggressive fluid resuscitation and the
      use of lactated Ringer solution seem to be beneficial in the treatment of AP.

PMID- 27888859
TI  - Treatment adherence is always worse than we think: an unresolved problem in
      inflammatory bowel disease.
AB  - New diagnostic and treatment tools are the "stars" of scientific meetings but
      other aspects may have an even greater impact on patients' lives. Several new
      studies presented at DDW (Digestive Disease Week) 2016 demonstrated that: a)
      treatment adherence continues to be suboptimal even in the most advanced health
      systems; b) lack of adherence correlates with low treatment effectiveness, with
      higher levels of intestinal damage and higher costs; and c) the factor most
      consistently associated with poor adherence is age (the younger the patient, the
      poorer the adherence). In any new programme aiming to enhance the quality of
      inflammatory bowel disease management, a key element should be the inclusion of
      new patient information and communication systems to increase treatment
      adherence. The new tools available in the telemedicine era provide an opportunity
      to improve the care of inflammatory bowel disease, but their success is limited
      by multiple problems. Overcoming these barriers should be our key goal in the
      next few years.

PMID- 27888860
TI  - Treatment of inflammatory bowel disease: what's new in Digestive Disease Week
      2016.
AB  - Inflammatory bowel disease is a chronic disorder of unknown aetiology that
      results from a pathologic response from both the innate and acquired immune
      systems, leading to chronic inflammation of the gastrointestinal tract. New drugs
      have been introduced into the therapeutic armamentarium of inflammatory bowel
      disease but are not effective in all patients; moreover, among initial
      responders, there have been reports of loss of response over time. In addition,
      these drugs sometimes have adverse effects and are often expensive. The present
      article reviews the studies presented at Digestive Disease Week 2016 that
      provided new data on the optimisation of currently approved treatments for
      inflammatory bowel disease, experience with recently approved drugs in clinical
      practice, and some studies on molecules that are under development for the
      treatment of these diseases.

PMID- 27888861
TI  - Inflammatory bowel disease in Digestive Disease Week 2016: advances in
      epidemiology, follow-up, treatment monitoring, optimisation and individual
      tailoring, and colon cancer prevention.
AB  - In Digestive Disease Week 2016, interesting data were presented on the eventual
      role of certain foods in inflammatory bowel disease, although the value of these
      data is relative. Also of interest were epidemiological studies, of which several
      analysed the natural history of the disease. Some presentations dealt with the
      search for individual predictive factors, a pressing need in clinical practice.
      Unfortunately, some of the findings presented were of dubious value. A study
      suggesting that a simple parameter as increased blood monocytes could be a clear
      predictive factor of poor outcome could perhaps be highlighted (the results were
      striking but had multiple limitations). In contrast, more interesting data were
      presented on monitoring and optimising biological therapy in the search for an
      individually-tailored approach. New studies were presented on the levels of
      distinct anti-TNF agents, vedolizumab and even ustekinumab. One study aimed to
      estimate the safety of anti-TNF agents on the basis of the patient's genetic (and
      clinical) features. There is no new evidence that will change our clinical
      practice. Equally, the data on colon cancer prevention will not modify our
      clinical practice, although one study reported a promising new strategy,
      consisting of the use of a new stool DNA test, with very promising results in the
      detection of high-grade dysplasia or colorectal cancer in these patients.

PMID- 27888862
TI  - Functional and motor gastrointestinal disorders.
AB  - This article discusses the most interesting presentations at Digestive Disease
      Week, held in San Diego, in the field of functional and motor gastrointestinal
      disorders. One of the most important contributions was undoubtedly the
      presentation of the new Rome IV diagnostic criteria for functional
      gastrointestinal disorders. We therefore devote some space in this article to
      explaining these new criteria in the most common functional disorders. In fact,
      there has already been discussion of data comparing Rome IV and Rome III criteria
      in the diagnosis of irritable bowel syndrome, confirming that the new criteria
      are somewhat more restrictive. From the physiopathological point of view, several
      studies have shown that the aggregation of physiopathological alterations
      increases symptom severity in distinct functional disorders. From the therapeutic
      point of view, more data were presented on the efficacy of acotiamide and its
      mechanisms of action in functional dyspepsia, the safety and efficacy of
      domperidone in patients with gastroparesis, and the efficacy of linaclotide both
      in irritable bowel syndrome and constipation. In irritable bowel syndrome, more
      data have come to light on the favourable results of a low FODMAP diet, with
      emphasis on its role in modifying the microbiota. Finally, long-term efficacy
      data were presented on the distinct treatment options in achalasia.

PMID- 27888863
TI  - Helicobacter pylori-related diseases.
AB  - This article describes the main conclusions drawn from the presentations on
      Helicobacter pylori infection in Digestive Diseases Week, 2016. Despite the
      undeniable widespread reduction in the prevalence of this infection, infection
      rates continue to be high in developing countries. The prevalence of
      clarithromycin, metronidazole and quinolone resistance is markedly high in most
      countries and continues to rise. The management of H. pylori infection in
      patients with peptic ulcers still leaves much to be desired. Although H. pylori
      eradication reduces the incidence of gastric adenocarcinoma, it does not
      completely avoid its appearance. The new rapid stool antigen tests show promising
      results. The efficacy of standard triple therapy is clearly inadequate and
      continues to decline, and cannot therefore be recommended. Vonoprazan, when
      associated with 2 antibiotics, is more effective than traditional proton pump
      inhibitors, especially in clarithromycin-resistant patients. Non-bismuth
      quadruple (concomitant) therapy achieves eradication rates of around 90% and has
      a good safety profile. Concomitant therapy is more effective and simpler than
      sequential therapy. Although some probiotics can increase the efficacy and
      tolerability of triple therapy, the utility of its association with quadruple
      concomitant therapy has not been established. If a first treatment with
      clarithromycin fails, both bismuth-containing quadruple therapy and levofloxacin
      containing triple therapy achieve good-but still suboptimal-results. The
      combination of bismuth and levofloxacin in the same regimen increases the
      efficacy of rescue therapy. The management of H. pylori infection by European
      gastroenterologists is widely heterogeneous and the eradication rates achieved by
      them are generally unacceptable. In Spain, the highest first-line eradication
      rate is obtained with quadruple concomitant therapy in 14-day regimens and with
      double doses of proton pump inhibitors; in second-line therapy, the use of
      levofloxacin- and bismuth-containing quadruple therapy improves the rates
      traditionally obtained with quinolones. On the other hand, there is a clear
      disconnect between the recommendations made in consensus documents and clinical
      practice in primary care.

PMID- 27888864
TI  - Oesophageal disease: gastroesophageal reflux disease, Barrett's oesophagus,
      achalasia and eosinophilic oesophagitis.
AB  - The most interesting conclusions and/or advances presented at Digestive Disease
      Week 2016 were the following: a) gastroesophageal reflux disease: proton pump
      inhibitor-refractory reflux disease is frequently associated with poor treatment
      adherence, psychiatric comorbidities and functional gastrointestinal disorders.
      These possible entities should be investigated in all cases of proton pump
      inhibitor-refractory reflux disease; b) Barrett's oesophagus: the efficacy of
      screening remains unclear; however, new minimally-invasive techniques such as the
      cytosponge allow more effective detection, both of Barrett's oesophagus and
      Barrett's oesophagus-associated dysplasia or neoplasia; c) achalasia: evidence
      indicates that peroral endoscopic myotomy is as effective as surgery and is a
      safer alternative; d) eosinophilic oesophagitis: high-dose proton pump inhibitors
      are required to rule out proton pump inhibitor-responsive eosinophilic
      oesophagitis; montelukast is not clearly effective in the treatment of
      eosinophilic oesophagitis, although moderate efficacy cannot be ruled out.

PMID- 27888865
TI  - Advances in gastrointestinal bleeding.
AB  - The main innovations of the latest meeting of the Gastroenterological Association
      (2016) concerning upper gastrointestinal bleeding from the clinician's
      perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the
      best accuracy in predicting the need for surgical intervention and hospital
      mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding
      are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest
      that treatment with hemospray does not seem to be superior to current standard
      treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a
      proton pump inhibitor may be effective in preventing haemorrhagic recurrence in
      patients taking aspirin, but this finding needs to be confirmed in further
      studies; e) There was confirmation of the need to re-introduce antiplatelet
      therapy as early as possible in patients with antiplatelet-associated
      gastrointestinal bleeding in order to prevent cardiovascular mortality; f)
      Routine clinical practice suggests that gastrointestinal or cardiovascular
      complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is
      associated with an increased incidence of gastrointestinal bleeding compared with
      apixaban or warfarin. At least half of the episodes are located in the lower
      gastrointestinal tract; h) Implant devices for external ventricular circulatory
      support are associated with early gastrointestinal bleeding in up to one third of
      patients; the bleeding is often secondary to arteriovenous malformations.

PMID- 27888866
TI  - Hereditary forms of colorectal cancer.
AB  - Colorectal cancer is one of the most frequent neoplasms in western countries; it
      is the third most common cancer in men after prostate and lung cancer and the
      second most common in women after breast cancer. Colorectal cancer is usually
      sporadic but in a small proportion is hereditary. The genetic cause is well
      established, allowing pre-symptomatic diagnosis in at-risk relatives. The present
      article reviews the most novel findings presented at the latest meeting of the
      American Gastroenterological Association on hereditary forms of colorectal
      cancer, especially Lynch syndrome and MUTYH-associated polyposis, as well as
      diverse organisational aspects that can favour the correct management of these
      patients and their relatives.

PMID- 27888867
TI  - Colorectal cancer screening.
AB  - In the latest meeting of the American Gastroenterological Association, several
      clinical studies were presented that aimed to evaluate the various colorectal
      cancer screening strategies, although most assessed the various aspects of faecal
      immunochemical testing (FIT) and colonoscopy. Data were presented from
      consecutive FIT-based screening rounds, confirming the importance of adherence to
      consecutive screening rounds, achieving a similar or superior diagnostic yield to
      endoscopic studies. There was confirmation of the importance of not delaying
      endoscopic study after a positive result. Participants with a negative FIT (score
      of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the
      importance of high-quality colonoscopy in colorectal cancer screening programmes.
      The implementation of high-quality colonoscopies has reduced mortality from
      proximal lesions and reduced interval cancers in various studies. Finally,
      participants with a normal colonoscopy result or with a small adenoma are at low
      risk for developing advanced neoplasms during follow-up.

PMID- 27888868
TI  - Novel findings in colorectal polyp surveillance.
AB  - Colorectal adenomas and serrated polyps are the best characterised premalignant
      lesions involved in the development of colorectal cancer (CRC). Therefore, the
      identification and removal of these lesions, as well as post-polypectomy
      surveillance of affected patients, are key goals in the field of CRC prevention.
      Current post-polypectomy surveillance strategies differ among the various
      scientific societies and have several limitations that hamper their application
      in clinical practice. First, current surveillance intervals are based only on
      polyp characteristics, excluding other potential clinical conditions, such as
      diabetes or metabolic syndrome. Second, serrated polyps and adenomas are
      considered separately, but there is no recommendation in cases of the
      simultaneous occurrence of both types of lesion. Third, the incorporation of
      endoscopic technologies implies an increase in polyp detection, whose clinical
      impact is controversial and directly affects the number of scheduled
      colonoscopies with an indication of surveillance. Some of the studies presented
      at the AGA (American Gastroenterological Association) meeting aimed to provide
      new evidence on the follow-up of colorectal polyps, with a view to optimising the
      applicability and suitability of current surveillance strategies.

PMID- 27888869
TI  - Latest advances in chronic pancreatitis.
AB  - This article summarizes some of the recent and clinically relevant advances in
      chronic pancreatitis. These advances mainly concern the definition of the
      disease, the etiological diagnosis of idiopathic disease, the correlation between
      fibrosis degree and pancreatic secretion in the early stages of chronic
      pancreatitis, the treatment of the disease and of pain, the clinical relevance of
      pancreatic exocrine insufficiency, and the diagnosis of autoimmune pancreatitis.
      A new mechanistic definition of chronic pancreatitis has been proposed. Genetic
      testing is mainly of help in patients with relapsing idiopathic pancreatitis. A
      significant correlation has been shown between the degree of pancreatic fibrosis
      as evaluated by elastography and pancreatic secretion of bicarbonate. New data
      supports the efficacy of antioxidants and simvastatin for the therapy of chronic
      pancreatitis. The pancreatoscopy-guided intraductal lithotripsy is an effective
      alternative to extracorporeal shock wave lithotripsy in patients with chronic
      calcifying pancreatitis. The presence of pancreatic exocrine insufficiency in
      patients with chronic pancreatitis is associated with a significant risk of
      cardiovascular events. Fine needle biopsy and contrast enhanced harmonic
      endoscopic ultrasonography are of help for the diagnosis of autoimmune
      pancreatitis and its differential diagnosis with pancreatic cancer.

PMID- 27888870
TI  - Latest advances in pancreatic tumours.
AB  - Pancreatic cancer continues to have a bleak prognosis. Hardly any therapeutic
      advances have been made in the last few years and consequently most efforts have
      focused on preventing its development and on diagnosing precursor lesions. In
      this regard, the use of statins as a preventive factor and the implementation of
      screening programmes in high-risk patients are gaining ground. In the field of
      treatment, there is greater focus on the role of neoadjuvant therapy in
      pancreatic cancer and on a multimodal approach to the disease, with few advances
      in effective novel therapies. Most studies concerned cystic tumours of the
      pancreas, especially intraductal mucinous papillary tumour, with its known
      potential for malignant transformation. Multiple studies were devoted to
      validation of the 2012 Fukuoka international guidelines and the highly
      controversial 2015 AGA guidelines. Notable among these studies were those
      demonstrating the suboptimal positive predictive value and questioning important
      aspects of the guidelines, such as discontinuation of follow-up or the criteria
      for surgical referral. Notable among diagnostic procedures were cystoscopy and
      endoscopic ultrasound-guided needle-based confocal laser endomicroscopy as the
      most promising techniques due to their high efficacy and negative predictive
      value in detecting mucinous cystic lesions. There were also a large number of
      studies on the natural history of intraductal papillary mucinous tumours, which
      help deepen knowledge of these entities and the search for predictive factors of
      cancer development.

PMID- 27888871
TI  - Dissecting the genetic background of multifactorial diseases and traits - A major
      challenge for genetic research.

PMID- 27888872
TI  - State-of-the-art Therapy for Advanced-stage Diffuse Large B-cell Lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) represents the most common lymphoid
      malignancy in adults, with a median age of 60 to 70 years. Clinical behavior is
      usually rapidly aggressive, with extranodal involvement in 40% of cases.
      Chemoimmunotherapy administered every 21 days is still the standard of care in
      the advanced stage. Optimization of frontline therapy and the amelioration of
      salvage strategies remain the most important targets in the treatment of patients
      with DLBCL. Novel drugs directed to specific molecular targets have been
      introduced as single agents or in addition to standard chemoimmunotherapy for the
      treatment of DLBCL.

PMID- 27888873
TI  - Molecular Classification of Diffuse Large B-cell Lymphoma: What Is Clinically
      Relevant?
AB  - Major progress in the understanding of diffuse large B-cell lymphoma (DLBCL)
      biology has been made in the last decade. Many specific compounds have now
      entered early phase clinical trials. However, further efforts are needed to find
      an accurate, fast, reproducible, and affordable technique to translate DLBCL
      subtype determination by gene expression profiles into clinical application. This
      article discusses the advantages and drawbacks of the currently available
      techniques of DLBCL subtype determination as well as important prognostic
      implications related to the cell of origin. Furthermore, the article provides a
      schematic description of how molecularly defined DLBCL subtypes could guide
      tailored therapy.

PMID- 27888874
TI  - Diffuse Large B-Cell Lymphoma: Should Limited-Stage Patients Be Treated
      Differently?
AB  - Diffuse large B-cell lymphoma presents as limited-stage disease in approximately
      30% of cases. Historically, therapy relied on a combined modality of abbreviated
      chemotherapy followed by involved-field radiotherapy (IFRT). Due to the apparent
      lack of long-term survival and the concern for delayed toxicity, chemotherapy
      only strategies are used more frequently. Treatment should take into account
      patient performance, clinical risks, and involvement sites. PET-guided approaches
      are being investigated. The risk of late relapse has been recognized,
      highlighting the importance of long-term follow-up. Future efforts must
      incorporate biological features to improve risk assessment, guide clinical
      decisions, and achieve an individualized therapy.

PMID- 27888875
TI  - Management of Relapsed Diffuse Large B-cell Lymphoma.
AB  - Second-line therapy options for patients with diffuse large B-cell lymphoma
      (DLBCL) that is refractory to, or relapses after, current rituximab-containing
      primary therapy continue to evolve. For younger patients, salvage therapy
      followed by intensive therapy and autologous stem cell transplant (ASCT) remains
      the treatment of choice for those with chemotherapy-sensitive disease.
      Combination therapy may be used for those who are not candidates for ASCT. In
      contrast, patients with DLBCL refractory to 2 lines of therapy have a very poor
      prognosis and generally short survival, and should be carefully considered for
      participation in clinical trials of novel approaches.

PMID- 27888876
TI  - Role of Positron Emission Tomography in Diffuse Large B-cell Lymphoma.
AB  - For initial staging and at end of treatment to document remission status, PET is
      the standard imaging modality. Interim scanning remains investigational.
      Surveillance PET is not beneficial in the majority of patients. PET has also been
      used to predict outcome in the pre-autologous transplant setting. PET in the pre
      allogeneic setting has a less established benefit. There is limited data on its
      use after transplant.

PMID- 27888878
TI  - The Spectrum of Double Hit Lymphomas.
AB  - Double-hit lymphomas (DHLs) characterize a unique subset of B-cell non-Hodgkin
      lymphomas. DHL typically presents in older adults with high-risk clinical
      features. This entity carries a significantly inferior prognosis compared with
      typical cases of diffuse large B-cell lymphoma; however, emerging literature can
      identify discrete clinical features within DHL that are associated with a
      favorable prognosis. Emerging literature is also demonstrating that intensive
      upfront treatment strategies may improve outcome. Diagnosis, prognostication, and
      management of DHL are reviewed, as well as potential future directions
      incorporating novel biologically targeted therapies. Finally, double-expressing
      lymphomas (DELs) will be discussed and contrasted with DHL.

PMID- 27888877
TI  - Promising Novel Agents for Aggressive B-Cell Lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in the
      western world. Current treatment regimens result in curing approximately 50% to
      60% of patients with DLBCL. In 2006, the Food and Drug Administration approved
      rituximab for use in the first-line treatment of patients with DLBCL in
      combination with anthracycline-based chemotherapy regimens. Since then, no other
      agents have been approved for the treatment of DLBCL. This article reviews recent
      data on the most promising agents in development for the treatment of DLBCL.

PMID- 27888879
TI  - Gray Zone Lymphoma: Current Diagnosis and Treatment Options.
AB  - The morphology of gray zone lymphoma (GZL) is variable with tumor cells spanning
      the spectrum of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin
      lymphoma. The immunophenotype is frequently discordant. Clinically, the initial
      case descriptions of GZL were primarily with mediastinal presentation; however, a
      nonmediastinal (systemic) clinical subtype is now recognized. Patients with GZL
      have high relapse rates. Recommended treatment of GZL is with a DLBCL-directed
      regimen with consideration for consolidative radiotherapy for bulk disease.
      Continued biologic examination of this entity is needed and there should be
      exploration toward integration of novel targeted therapeutic agents into the
      treatment paradigm of GZL.

PMID- 27888880
TI  - Optimizing Outcomes in Primary Mediastinal B-cell Lymphoma.
AB  - Primary mediastinal B-cell lymphoma is characterized by a high chance of cure,
      and cured patients have a long disease-free life-expectancy; however, prognosis
      is severe in the case of relapsed or refractory disease. The initial use of the
      most effective chemoimmunotherapy regimen is therefore crucial. Understanding who
      will benefit from postinduction radiotherapy is also of paramount importance;
      positron emission tomography may be a reliable guide for physicians in
      determining which patients will require consolidation. New drugs with mechanisms
      of action including the most relevant biologic features of the tumor may allow
      better disease control.

PMID- 27888881
TI  - Central Nervous System Prophylaxis for Aggressive B-cell Lymphoma: Who, What, and
      When?
AB  - Central nervous system (CNS) relapse of aggressive B-cell lymphoma is a rare but
      serious complication with poor survival. Different approaches have been used to
      define risks factors for CNS relapse and establish prophylactic measures.
      Although patients with low or intermediate risk of CNS relapse should not undergo
      special diagnostic or therapeutic measures, CNS MRI as well as cytology and flow
      cytometry of the cerebrospinal fluid are suggested for high-risk patients (and
      patients with testicular involvement) at diagnosis, and prophylactic high-dose
      methotrexate in patients without proven CNS involvement. Future risk and
      treatment models may include molecular features and new treatment options.

PMID- 27888883
TI  - Transformed Lymphoma.
AB  - Transformed lymphoma is a complex syndrome that encompasses an array of different
      underlying low-grade lymphoproliferative conditions transforming into more
      aggressive disease as manifest by morphologic, clinical, and genetic features.
      Over the last decade, advances in chemoimmunotherapy have led to new options.
      Knowledge surrounding the genetic changes driving the process of transformation
      is leading to novel targeted therapies. This article focuses on the
      transformation of chronic lymphocytic leukemia and follicular lymphoma into
      diffuse large B-cell lymphoma.

PMID- 27888885
TI  - Mantle Cell Lymphoma: Is It Time for a New Treatment Paradigm?
AB  - Mantle cell lymphoma is a relatively rare subtype of lymphoma with a great deal
      of heterogeneity, both clinically and biologically. Since its recognition as a
      separate entity in the early 1990s though, consistent efforts have led to a
      significant improvement of overall survival, from a median overall survival of
      2.5 years initially to 5-7 years currently. This decades-long and stepwise
      progress, summarized in the article, definitely accelerated recently, shedding
      light on a changing paradigm.

PMID- 27888884
TI  - Update on Burkitt Lymphoma.
AB  - Because of its rarity and high curability, progress in advancing therapeutics in
      Burkitt lymphoma (BL) has been difficult. Over recent years, several new
      mutations that cooperate with MYC have been identified, and this has paved the
      way for testing novel agents in the disease. One of the challenges of most
      standard approaches typically used is severe treatment-related toxicity that
      often leads to discontinuation of therapy. To that point, there has been recent
      success developing intermediate intensity approaches that are well tolerated in
      all patient groups and maintain high cure rates in a multicenter setting.

PMID- 27888886
TI  - The Increasing Complexity of Aggressive B-cell Lymphoma.

PMID- 27888882
TI  - The Challenge of Primary Central Nervous System Lymphoma.
AB  - Primary central nervous system (CNS) lymphoma is a challenging subtypes of
      aggressive non-Hodgkin lymphoma. Emerging clinical data suggest that optimized
      outcomes are achieved with dose-intensive CNS-penetrant chemotherapy and avoiding
      whole brain radiotherapy. Anti-CD20 antibody-based immunotherapy as a component
      of high-dose methotrexate-based induction programs may contribute to improved
      outcomes. An accumulation of insights into the molecular and cellular basis of
      disease pathogenesis is providing a foundation for the generation of molecular
      tools to facilitate diagnosis as well as a roadmap for integration of targeted
      therapy within the developing therapeutic armamentarium for this challenging
      brain tumor.

PMID- 27888887
TI  - Soft Tissue Principles to Minimize Scarring: An Overview.
AB  - This article is a broad overview of measures and techniques that can be used to
      minimize soft tissue scarring.

PMID- 27888888
TI  - Laser-Assisted Delivery to Treat Facial Scars.
AB  - Treatment of facial scars is a multispecialty endeavor for optimal patient
      recovery. One new innovation helping in facial scar treatments are lasers.
      Fractional laser predictably (tunable) disrupts the barrier of the skin creating
      deep channels that allow the delivery of drug and cellular materials; this is
      called laser-assisted drug delivery (LAD). Without exception thus far, LAD has
      been found to enhance the local uptake of any drug or substance applied to the
      skin. These zones may be used postoperatively to deliver drugs and other
      substances to create an enhanced scar therapeutic response to drug or substance
      applied to the skin.

PMID- 27888889
TI  - Skin Color and Pigmentation in Ethnic Skin.
AB  - Skin coloration is highly diverse, partly due to the presence of pigmentation.
      Color variation is related to the extent of ultraviolet radiation exposure, as
      well as other factors. Inherent skin coloration arises from differences in basal
      epidermal melanin amount and type. Skin color is influenced by both the quantity
      and distribution of melanocytes. The effectiveness of inherent pigmentation for
      protecting living cells also varies. This article discusses skin color,
      pigmentation, and ethnicity in relation to clinical practice. Color perception,
      skin typing/classification, and quantitation of pigmentation are reviewed in
      relation to ethnicity, environmental stresses/irritants, and potential treatment
      effects.

PMID- 27888891
TI  - Periorbital Scar Correction.
AB  - Periorbital scarring with eyelid retraction can have serious visual effects and
      can lead to loss of vision or even loss of the eye. Understanding of eyelid
      anatomy and the delicate balance of its structural supports is critical for the
      identification of the eyelid disorder responsible for the cicatrix and helps to
      guide treatment. The 2-finger test and lateral distraction of the lid can also be
      of significant help in proper diagnosis of the underlying disorder. Proper
      reconstruction with respect to the anterior and posterior lamellae helps to
      ensure a favorable outcome.

PMID- 27888890
TI  - Management of Forehead Scars.
AB  - This article provides an overview of scar management within the forehead region.
      It addresses the unique challenges specific to the treatment of forehead wounds.
      A logical, stepwise approach is used. A subsite based treatment algorithm is
      provided along with a review of current best practices. Pertinent case examples
      are included for demonstration purposes.

PMID- 27888892
TI  - Treating Scars of the Cheek Region.
AB  - Scars of the cheek resulting from all causes can extol significant psychological
      toll. The cheek is the largest facial subunit and visually and aesthetically
      prominent making scars in this region difficult to ignore. An approach to scar
      management that targets specific characteristics of a scar using a combination of
      surgical and nonsurgical modalities can significantly improve the appearance of
      most scars. The ideal time to revise a scar should be based on the extent of scar
      maturation and presence or absence of any functional distortion.

PMID- 27888893
TI  - Unique Clinical Aspects of Nasal Scarring.
AB  - Various methods are available for refining scars of the external nose and optimal
      scar revision frequently requires the utilization of multiple techniques.
      Differing anatomy of nasal subunits and their underlying structural framework
      limit surgical options in nasal scar revision compared with other areas of the
      face. An understanding of a variety of laser technologies and their specific
      applications can vastly aid in fine, controlled scar revision. Achieving optimal
      scar reduction regularly requires multiple stages of intervention, close follow
      up, and repeat procedures.

PMID- 27888894
TI  - Treating Scars of the Chin and Perioral Region.
AB  - Lip and chin scarring occurs owing to reconstruction of congenital, cancer
      resection, or traumatic defects. Knowledge of lip anatomy and function is
      critical to optimize results. Realistic expectations should be established before
      intervention. Scar revision and reconstruction is ideally performed with a
      subunit approach, placing scars along aesthetic borders and performing subunit
      reconstruction to camouflage scars. Surgical techniques include direct excision,
      scar reorientation, local flap rearrangement, pedicled flaps, and regional or
      free flaps. Resurfacing/adjunctive procedures play important roles in the
      treatment of scars. This article reviews the anatomy, patient assessment, and
      techniques used in scar revision of the perioral region.

PMID- 27888895
TI  - Treating Scars in the Auricle Region.
AB  - This article provides a review of the surgical and nonsurgical options available
      to manage a variety of auricular scars. The basics of wound healing are discussed
      in addition to the etiology of keloids and the cauliflower ear. Many auricular
      scars can be revised with scar excision techniques, but separate discussions for
      the treatment of keloids and the cauliflower ear are provided. The management
      plan for auricular scarring requires appropriate patient counseling regarding the
      risk of recurrence in keloids, regrowth of scar tissue in cauliflower ears, scar
      hypertrophy at the line of closure, widening of the scar, and persisting ear
      contour deformities.

PMID- 27888896
TI  - Treatment of Scalp Scars.
AB  - The scalp presents many challenges to the reconstructive surgeon given its
      visible nature and the various considerations that must be given for optimal
      reconstruction. In this article, we review the anatomy of the scalp, the various
      options for reconstruction, and important considerations for improving the
      chances of optimal reconstruction of scalp defects.

PMID- 27888897
TI  - Treating Scars on the Oral Mucosa.
AB  - Mucosal wounds tend to heal more rapidly than skin wounds and with minimal to no
      scar formation and hence have a minimal impact on function or aesthetics. This is
      likely due to differences in the magnitude and timing of the various factors that
      contribute to wound healing. Some examples of these differences are fibroblast
      proliferation, transforming growth factor-beta, macrophages, neutrophils, and T
      cells. Other factors, such as the moist environment, contribute to the favorable
      wound-healing characteristics of mucosa.

PMID- 27888899
TI  - Facial Scar Management.

PMID- 27888898
TI  - Treating Scars to the Neck.
AB  - Scarring of the neck affects millions of people every year. The appearance of
      neck scarring can be disturbing both physically and psychologically. Scarring of
      the neck can be accompanied by morbidities because of the limitation of
      functional motion of the neck. Treatment options and modalities for reduction and
      prevention of scar formation include topical steroids, intralesional steroids,
      interferon, 5-fluorouracil, silicone gel, radiation, laser therapy, and
      surgeries. There is no general consensus in the literature as to the optimal
      treatment of neck scarring. Patients should understand that the scar is likely to
      be improved but not eliminated by treatment.

PMID- 27888900
TI  - ?

PMID- 27888901
TI  - [Monoclonal antibodies against PCSK9: from bench to clinic].
AB  - Antibodies are glycoproteins with high specificity binding to multiple antigens
      due to the large number of structural conformations of the variable chains.
      Hybridoma technology (fusion of myeloma cells with immunoglobulin-producing
      lymphocytes) has allowed the synthesis of large quantities of unique antibodies
      (monoclonal [mAb]). mAbs were initially murine. Subsequently, chimeric mAbs were
      developed, followed by humanized mAbs and finally human mAbs. The high
      selectivity and good tolerance of human mAbs allows their therapeutic
      administration to block specific exogenous or endogenous molecules. Selective
      human mAbs to the catalytic domain of PCSK9 have recently been developed. These
      antibodies block PCSK9, favour low-density lipoprotein receptor recycling and
      markedly reduce circulating cholesterol. Preliminary studies indicate that
      lowering cholesterol through anti-PCSK9 antibodies may significantly reduce the
      cardiovascular complications of arteriosclerosis.

PMID- 27888903
TI  - [PCSK9: Structure and function. PCSK9 and low-density lipoprotein receptor.
      Mutations and their effects].
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density
      lipoprotein receptor (LDLr) and then targets it for lysosomal degradation in
      cells, thus preventing LDLr from recycling back to the hepatocyte surface, with a
      consequent decrease in LDLr density and clearance of LDL-cholesterol (LDLc).
      There have been reports of both gain-of-function mutations in the PCSK9 gene that
      cause a marked increase in LDLc conentrations and loss-of-function mutations,
      which lead to modest reductions in LDLc and low rates of coronary heart disease.
      The PCSK9 gene has become a promising therapeutic target to reduce blood
      cholesterol levels. This review discusses the most interesting recent data on
      PCSK9 regulation and its molecular function in cholesterol homeostasis.

PMID- 27888902
TI  - [Unmet needs: patients with statin intolerance or familial hypercholesterolemia].
AB  - The achievement of low-density lipoprotein (LDL) therapeutic targets is
      especially difficult in some patients at high cardiovascular risk. These patients
      include persons with statin intolerance and those with very high LDL cholesterol
      (LDLc) levels such as persons with familial hypercholesterolemia. The proportion
      of statin-intolerant patients is between 7% and 29%. Alternative lipid-lowering
      drugs (including ezetimibe) are less effective and are not free from adverse
      effects. Both alirocumab, with the ODYSSEY ALTERNATIVE study, and evolocumab,
      with the GAUSS study, have shown strong lipid-lowering efficacy, with much
      greater tolerability than currently available alternatives, with the result that
      a larger number of patients achieve therapeutic targets. In familial
      hypercholesterolemia, the monogenic metabolic disease most frequently associated
      with high cardiovascular risk, early intervention is cost-effective. Although
      statins have substantially improved the prognosis of familial
      hypercholesterolemia, many affected individuals are far from achieving the
      recommended therapeutic targets. In this patient group, PCSK9 inhibition with
      monoclonal antibodies has also been shown to be highly effective in reducing
      LDLc, especially in heterozygous individuals. The studies performed to date have
      shown that these drugs are safe and effective and can help many patients with
      familial hypercholesterolemia to drastically reduce their cardiovascular risk.

PMID- 27888904
TI  - [Anti-PCSK9 antibodies in type 2 diabetes and secondary prevention of
      cardiovascular diseases].
AB  - Patients with type 2 diabetes are considered to have the same cardiovascular risk
      as patients with ischemia. However, the degree of lipid control in diabetic and
      ischemic patients remains highly deficient. The availability of new agents, such
      as anti-PCSK9 monoclonal antibodies, could represent a notable advance in meeting
      this unmet need. Alirocumab and evolucumab, followed by bococizumab, are
      currently under the advanced phase of research. A growing database has
      demonstrated a relationship between glucose metabolism, body weight and PCSK9
      function, but the clinical implications of this relationship have not been well
      defined. A broad programme of clinical trials has demonstrated that these agents
      decrease low-density lipoprotein cholesterol by more than 60% and also decrease
      apolipoprotein B and lipoprotein (a), showing a good tolerability and safety
      profile. In addition, post hoc analyses of phase 2 and 3 trials have observed
      that when these agents are associated with conventional lipid-lowering they
      reduce cardiovascular risk by more than 50%. Currently, 4 large clinical trials
      of cardiovascular prevention are underway in patients with ischemia or high
      cardiovascular risk. The aim of these trials is to define the role of anti-PCSK9
      agents in the treatment of dyslipidemia and the prevention of cardiovascular
      disease in patients with ischemia and high cardiovascular risk.

PMID- 27888905
TI  - ?

PMID- 27888906
TI  - [Lipid-lowering drugs and PCSK9].
AB  - PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic
      degradation of the LDL receptor and consequently decreases LDL receptor density
      and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an
      enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The
      decrease of the hepatic intracellular cholesterol pool produced by these drugs
      upregulates the activity of the SREBP2 transcription factor, which subsequently
      stimulates the expression of the LDL receptor gene, an effect that is followed by
      an increase in the serum concentration of PCSK9. This article aims to review the
      effects of different lipid-lowering drugs on plasma PCSK9 concentrations.
      Overall, statins increase blood PCSK9 levels, an effect that is enhanced by
      ezetimibe. In contrast, others drugs, such as fibrates and niacin, could decrease
      PCSK9 levels.

PMID- 27888907
TI  - Classification of Chronic Rhinosinusitis-Working Toward Personalized Diagnosis.
AB  - An estimated 4.5% of total US health care dollars have been devoted to mitigating
      chronic rhinosinusitis. The most recalcitrant of these patients undergo surgery,
      which fails to improve symptoms in approximately 25% of patients. Recent advances
      in informational, microbiomic, and genomic analysis have introduced the first set
      of tools that patients, physicians, politicians, and payers can apply to better
      forecast which patients will respond favorably to endoscopic sinus surgery. This
      article summarizes the forces driving the application of personalized medicine to
      CRS and how new advances can be applied to clinical practice.

PMID- 27888908
TI  - Office Procedures in Refractory Chronic Rhinosinusitis.
AB  - Office procedures in chronic rhinosinusitis (CRS) can be considered before and
      after medical management, as well as before and after surgical management. This
      article focuses specifically on refractory CRS, meaning those patients who have
      failed medical and surgical management already. The options available in the
      management of refractory CRS depend on the personnel, equipment, and
      instrumentation available in the office setting; surgeon experience; and patient
      suitability and tolerability. This article provides readers with possible
      procedural options that can be done in their clinics with indications, patient
      selection, potential complications, and postoperative considerations.

PMID- 27888909
TI  - Topical Therapies for Refractory Chronic Rhinosinusitis.
AB  - Topical therapy has become an important tool in the otolaryngologist's
      armamentarium for refractory chronic rhinosinusitis (CRS). Daily high-volume
      sinonasal saline irrigation and standard metered-dose topical nasal steroid
      therapy are supported by the most evidence. Nonstandard topical sinonasal steroid
      therapies are a potential option for refractory CRS. Current evidence recommends
      against the use of topical antifungal therapy and topical antibiotic therapy
      delivered using spray and nebulized techniques in routine cases of CRS. Stents
      are a new modality with preliminary data showing they are an option when
      traditional treatment has failed. Further research with long-term effects and
      outcomes studies for refractory CRS are needed.

PMID- 27888910
TI  - Genetic and Immune Dysregulation in Chronic Rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is a prevalent condition that is heterogeneous in
      disease characteristics and multifactorial in cause. Although sinonasal mucosal
      inflammation in CRS is often either reversible or well-managed medically and
      surgically, a significant proportion of patients has a refractory form of CRS
      despite maximal therapy. Two of the several described factors thought to
      contribute to disease recalcitrance are genetic influences and dysfunction of the
      host immune system. Current evidence for a genetic basis of CRS is reviewed, as
      it pertains to putative abnormalities in innate and adaptive immune function. The
      role of systemic immunodeficiencies in refractory CRS is discussed.

PMID- 27888911
TI  - Revision Functional Endoscopic Sinus Surgery.
AB  - Refractory chronic rhinosinusitis can be challenging to treat. Initial treatment
      focuses on medical and nonsurgical treatments. If these treatments fail, revision
      endoscopic sinus surgery is an option. A plan for revision surgery must address
      anatomic factors contributing to recurrence. Preoperative imaging and sinonasal
      endoscopy are systematically reviewed; areas of disease and "danger" zones are
      identified. Traditional anatomic landmarks are often obscured or absent; thus, a
      set of consistent landmarks (unchanged despite prior surgery) are used to
      navigate the revision endoscopic sinus surgery. Wide sinusotomies permit
      visualization and access to disease intraoperatively. Large sinus openings also
      facilitate post-operative debridements in clinic, endoscopic disease monitoring,
      and topical sinus therapy.

PMID- 27888912
TI  - Extended Endoscopic and Open Sinus Surgery for Refractory Chronic Rhinosinusitis.
AB  - This review discusses extended endoscopic and open sinus surgery for refractory
      chronic rhinosinusitis. Extended maxillary sinus surgery including endoscopic
      maxillary mega-antrostomy, endoscopic modified medial maxillectomy, and inferior
      meatal antrostomy are described. Total/complete ethmoidectomy with mucosal
      stripping (nasalization) is discussed. Extended endoscopic sphenoid sinus
      procedures as well as their indications and potential risks are reviewed.
      Extended endoscopic frontal sinus procedures, such the modified Lothrop
      procedure, are described. Extended open sinus surgical procedures, such as the
      Caldwell-Luc approach, frontal sinus trephine procedure, external
      frontoethmoidectomy, frontal sinus osteoplastic flap with or without
      obliteration, and cranialization, are discussed.

PMID- 27888913
TI  - A Practical Approach to Refractory Chronic Rhinosinusitis.
AB  - Patients with refractory chronic rhinosinusitis, by definition, have persistent,
      poorly controlled symptoms and objective inflammatory findings despite prior
      medical and surgical therapy. These patients represent a diagnostic and treatment
      challenge given the complexity of the underlying disease factors and the
      limitations in available management options. This article presents a practical
      framework for clinical evaluation and treatment. Germane to discussion are
      emerging concepts in refractory chronic rhinosinusitis that will likely have
      important implications in the near future.

PMID- 27888915
TI  - Biofilm and Osteitis in Refractory Chronic Rhinosinusitis.
AB  - Our understanding of chronic rhinosinusitis (CRS) show biofilm and osteitis play
      a role in the disease's pathogenesis and refractory. Studies point to its role in
      pathogenesis and poor prognosis. Outside the research laboratory, biofilm
      detection remains difficult and specific treatment remains elusive. It is
      believed that osteitis is a nidus of inflammation and occurs more commonly in
      patients with refractory CRS. However, osteitis may be exacerbated by surgery and
      a marker of refractory disease, not a causative agent. Surgery remains the
      mainstay treatment for biofilm and osteitis with mechanical disruption and
      removal of disease load providing the most effective treatment.

PMID- 27888916
TI  - Refractory Chronic Rhinosinusitis with Nasal Polyposis.
AB  - Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents a subset of
      chronic sinusitis with various causes. Some forms of the disease are driven by
      allergy, often in association with asthma. Refractory CRSwNP can be associated
      with cystic fibrosis and other clinical syndromes. More recent literature is
      presented regarding roles of innate immunity and superantigens. Effective
      treatment of CRSwNP requires careful endoscopic sinus surgery followed by an
      individualized treatment plan that often includes oral and topical steroids.
      Recidivism of polyps is common, and patients require long-term follow-up.

PMID- 27888917
TI  - Aspirin-Exacerbated Respiratory Disease.
AB  - Aspirin-exacerbated respiratory disease (AERD) is characterized by the triad of
      asthma, sinonasal polyposis, and aspirin intolerance. The hallmark of the disease
      is baseline overproduction of cysteinyl leukotrienes via the 5-lipoxygenase
      pathway, exacerbated by ingestion of aspirin. Patients with AERD have high rates
      of recidivistic polyposis following sinus surgery, although the improvement in
      quality of life following surgery is similar to aspirin-tolerant patients. The
      diagnosis is secured by a positive aspirin provocation test, usually administered
      by a medical allergist. Aspirin therapy is a unique treatment consideration for
      patients with AERD.

PMID- 27888918
TI  - Systemic and Odontogenic Etiologies in Chronic Rhinosinusitis.
AB  - Systemic and odontogenic etiologies of chronic rhinosinusitis, although rare, are
      an integral consideration in the comprehensive management of patients with
      sinonasal disease. Proper knowledge and timely recognition of each disease
      process, with referrals to appropriate consultants, will facilitate treatment,
      because many of these conditions require both local and systemic therapy. In some
      instances, medical therapy plays a pivotal role, with surgery being a
      supplemental treatment technique. We review the most commonly encountered
      systemic etiologies of chronic rhinosinusitis and odontogenic sinusitis,
      including clinical presentation, diagnosis, management, and treatment outcomes.

PMID- 27888919
TI  - Chronic Rhinosinusitis: A "Simple" Complex Condition.

PMID- 27888914
TI  - Bacterial Pathogens and the Microbiome.
AB  - Bacterial pathogens and microbiome alterations can contribute to the initiation
      and propagation of mucosal inflammation in chronic rhinosinusitis (CRS). In this
      article, the authors review the clinical and research implications of key
      pathogens, discuss the role of the microbiome, and connect bacteria to mechanisms
      of mucosal immunity relevant in CRS.

PMID- 27888920
TI  - Refractory Chronic Rhinosinusitis.

PMID- 27888921
TI  - Editorial.

PMID- 27888922
TI  - Thermal sensation prediction by soft computing methodology.
AB  - Thermal comfort in open urban areas is very factor based on environmental point
      of view. Therefore it is need to fulfill demands for suitable thermal comfort
      during urban planning and design. Thermal comfort can be modeled based on
      climatic parameters and other factors. The factors are variables and they are
      changed throughout the year and days. Therefore there is need to establish an
      algorithm for thermal comfort prediction according to the input variables. The
      prediction results could be used for planning of time of usage of urban areas.
      Since it is very nonlinear task, in this investigation was applied soft computing
      methodology in order to predict the thermal comfort. The main goal was to apply
      extreme leaning machine (ELM) for forecasting of physiological equivalent
      temperature (PET) values. Temperature, pressure, wind speed and irradiance were
      used as inputs. The prediction results are compared with some benchmark models.
      Based on the results ELM can be used effectively in forecasting of PET.

PMID- 27888923
TI  - Determination of time of death in forensic science via a 3-D whole body heat
      transfer model.
AB  - This study is focused on developing a whole body heat transfer model to
      accurately simulate temperature decay in a body postmortem. The initial steady
      state temperature field is simulated first and the calculated weighted average
      body temperature is used to determine the overall heat transfer coefficient at
      the skin surface, based on thermal equilibrium before death. The transient
      temperature field postmortem is then simulated using the same boundary condition
      and the temperature decay curves at several body locations are generated for a
      time frame of 24h. For practical purposes, curve fitting techniques are used to
      replace the simulations with a proposed exponential formula with an initial time
      delay. It is shown that the obtained temperature field in the human body agrees
      very well with that in the literature. The proposed exponential formula provides
      an excellent fit with an R2 value larger than 0.998. For the brain and internal
      organ sites, the initial time delay varies from 1.6 to 2.9h, when the temperature
      at the measuring site does not change significantly from its original value. The
      curve-fitted time constant provides the measurement window after death to be
      between 8h and 31h if the brain site is used, while it increases 60-95% at the
      internal organ site. The time constant is larger when the body is exposed to
      colder air, since a person usually wears more clothing when it is cold outside to
      keep the body warm and comfortable. We conclude that a one-size-fits-all approach
      would lead to incorrect estimation of time of death and it is crucial to generate
      a database of cooling curves taking into consideration all the important factors
      such as body size and shape, environmental conditions, etc., therefore, leading
      to accurate determination of time of death.

PMID- 27888925
TI  - Inverse investigation of non-Fourier heat conduction in tissue.
AB  - This paper attempts to describe the heat conduction in tissue using the dual
      phase-lag mode. Evaluating the thermo-physical parameters is one of the ways to
      certify the thermal behavior. As a result, the paper simultaneously and inversely
      estimates the values of tauq, tauT and alpha for bologna based on the dual-phase
      lag mode with the measurement data in the literature. The inconsistence in theory
      discovered in the literatures is eliminated. The calculated results of
      temperature variation with the estimated values of tauq, tauT and alpha at the
      measurement location are very close to the experimental data and address the
      rationality of the present results.

PMID- 27888924
TI  - Triangular node for Transmission-Line Modeling (TLM) applied to bio-heat
      transfer.
AB  - Transmission-Line Modeling (TLM) is a numerical method used to solve complex and
      time-domain bio-heat transfer problems. In TLM, rectangles are used to discretize
      two-dimensional problems. The drawback in using rectangular shapes is that
      instead of refining only the domain of interest, a large additional domain will
      also be refined in the x and y axes, which results in increased computational
      time and memory space. In this paper, we developed a triangular node for TLM
      applied to bio-heat transfer that does not have the drawback associated with the
      rectangular nodes. The model includes heat source, blood perfusion (advection),
      boundary conditions and initial conditions. The boundary conditions could be
      adiabatic, temperature, heat flux, or convection. A matrix equation for TLM,
      which simplifies the solution of time-domain problems or solves steady-state
      problems, was also developed. The predicted results were compared against results
      obtained from the solution of a simplified two-dimensional problem, and they
      agreed within 1% for a mesh length of triangular faces of 59um+/-9um (mean+/
      standard deviation) and a time step of 1ms.

PMID- 27888926
TI  - MicroCT image based simulation to design heating protocols in magnetic
      nanoparticle hyperthermia for cancer treatment.
AB  - OBJECTIVES: The objective is to design heating protocols to completely damage PC3
      tumors after a single magnetic nanoparticle hyperthermia session with minimal
      collateral thermal damage, based on microCT image generated tumor and mouse
      models. METHODS: Tumor geometries and volumetric heat generation rate
      distributions that are generated from microCT scans in our previous study are
      imported into COMSOL 4.3(r) multiphysics for heat transfer simulations and
      heating protocol design using the Arrhenius damage model. Then, parametric
      studies are performed to evaluate how significantly the infusion rate affects the
      protocol design and its resulted collateral thermal damage. RESULTS: The
      simulated temperature field in the generated tumor geometry and volumetric heat
      generation rate distribution are reasonable and correlates well with the amount
      of the total thermal energy deposited into the tumors. The time needed for
      complete thermal damage is determined to be approximately 12min or 25min if one
      uses the Arrhenius integral Omega equal to 1 or 4 as the damage threshold, when
      the infusion rate is 3MUL/min. The heating time increases 26% or 91% in the
      higher infusion rate groups of 4 or 5MUL/min, respectively. Collateral thermal
      damage to the surrounding tissue is also assessed. Although the two larger
      infusion rate groups can still cause thermal damage to the entire tumor, the
      collateral thermal damage would have exceeded the design criterion of 5%, while
      the assessment criterion is acceptable only in the infusion rate group of
      3MUL/min. Based on the results of this study, we identify an injection strategy
      and heating protocols to be implemented in future animal experiments to evaluate
      treatment efficacy for model validation.

PMID- 27888927
TI  - Thermal behavior of human eye in relation with change in blood perfusion,
      porosity, evaporation and ambient temperature.
AB  - Extreme environmental and physiological conditions present challenges for thermal
      processes in body tissues including multi-layered human eye. A mathematical model
      has been formulated in this direction to study the thermal behavior of the human
      eye in relation with the change in blood perfusion, porosity, evaporation and
      environmental temperatures. In this study, a comprehensive thermal analysis has
      been performed on the multi-layered eye using Pennes' bio-heat equation with
      appropriate boundary and interface conditions. The variational finite element
      method and MATLAB software were used for the solution purpose and simulation of
      the results. The thermoregulatory effect due to blood perfusion rate, porosity,
      ambient temperature and evaporation at various regions of human eye was
      illustrated mathematically and graphically. The main applications of this model
      are associated with the medical sciences while performing laser therapy and other
      thermoregulatory investigation on human eye.

PMID- 27888928
TI  - Analytical prediction of sub-surface thermal history in translucent tissue
      phantoms during plasmonic photo-thermotherapy (PPTT).
AB  - Knowledge of thermal history and/or distribution in biological tissues during
      laser based hyperthermia is essential to achieve necrosis of tumour/carcinoma
      cells. A semi-analytical model to predict sub-surface thermal distribution in
      translucent, soft, tissue mimics has been proposed. The model can accurately
      predict the spatio-temporal temperature variations along depth and the anomalous
      thermal behaviour in such media, viz. occurrence of sub-surface temperature
      peaks. Based on optical and thermal properties, the augmented temperature and
      shift of the peak positions in case of gold nanostructure mediated tissue phantom
      hyperthermia can be predicted. Employing inverse approach, the absorption
      coefficient of nano-graphene infused tissue mimics is determined from the peak
      temperature and found to provide appreciably accurate predictions along depth.
      Furthermore, a simplistic, dimensionally consistent correlation to theoretically
      determine the position of the peak in such media is proposed and found to be
      consistent with experiments and computations. The model shows promise in
      predicting thermal distribution induced by lasers in tissues and deduction of
      therapeutic hyperthermia parameters, thereby assisting clinical procedures by
      providing a priori estimates.

PMID- 27888929
TI  - Modeling of heat transfer in a vascular tissue-like medium during an interstitial
      hyperthermia process.
AB  - This paper aims to evaluate the role of small vessels in heat transfer mechanisms
      of a tissue-like medium during local intensive heating processes, for example, an
      interstitial hyperthermia treatment. To this purpose, a cylindrical tissue with
      two co- and counter-current vascular networks and a central heat source is
      introduced. Next, the energy equations of tissue, supply fluid (arterial blood),
      and return fluid (venous blood) are derived using porous media approach. Then, a
      2D computer code is developed to predict the temperature of blood (fluid phase)
      and tissue (solid phase) by conventional volume averaging method and a more
      realistic solution method. In latter method, despite the volume averaging the
      blood of interconnect capillaries is separated from the arterial and venous blood
      phases. It is found that in addition to blood perfusion rate, the arrangement of
      vascular network has considerable effects on the pattern and amount of the
      achieved temperature. In contrast to counter-current network, the co-current
      network of vessels leads to considerable asymmetric pattern of temperature
      contours and relocation of heat affected zone along the blood flow direction.
      However this relocation can be prevented by changing the site of hyperthermia
      heat source. The results show that the cooling effect of co-current blood vessels
      during of interstitial heating is more efficient. Despite much anatomical
      dissimilarities, these findings can be useful in designing of protocols for
      hyperthermia cancer treatment of living tissue.

PMID- 27888930
TI  - Thermoregulation in premature infants: A mathematical model.
AB  - PURPOSE: In 2010, approximately 14.9 million babies (11.1%) were born preterm.
      Because preterm infants suffer from an immature thermoregulatory system they have
      difficulty maintaining their core body temperature at a constant level.
      Therefore, it is essential to maintain their temperature at, ideally, around 37
      degrees C. For this, mathematical models can provide detailed insight into heat
      transfer processes and body-environment interactions for clinical applications.
      METHODS: A new multi-node mathematical model of the thermoregulatory system of
      newborn infants is presented. It comprises seven compartments, one spherical and
      six cylindrical, which represent the head, thorax, abdomen, arms and legs,
      respectively. The model is customizable, i.e. it meets individual characteristics
      of the neonate (e.g. gestational age, postnatal age, weight and length) which
      play an important role in heat transfer mechanisms. The model was validated
      during thermal neutrality and in a transient thermal environment. RESULTS: During
      thermal neutrality the model accurately predicted skin and core temperatures. The
      difference in mean core temperature between measurements and simulations averaged
      0.25+/-0.21 degrees C and that of skin temperature averaged 0.36+/-0.36 degrees
      C. During transient thermal conditions, our approach simulated the
      thermoregulatory dynamics/responses. Here, for all infants, the mean absolute
      error between core temperatures averaged 0.12+/-0.11 degrees C and that of skin
      temperatures hovered around 0.30 degrees C. CONCLUSIONS: The mathematical model
      appears able to predict core and skin temperatures during thermal neutrality and
      in case of a transient thermal conditions.

PMID- 27888931
TI  - A study on thermal damage during hyperthermia treatment based on DPL model for
      multilayer tissues using finite element Legendre wavelet Galerkin approach.
AB  - Hyperthermia is a process that uses heat from the spatial heat source to kill
      cancerous cells without damaging the surrounding healthy tissues. Efficacy of
      hyperthermia technique is related to achieve temperature at the infected cells
      during the treatment process. A mathematical model on heat transfer in multilayer
      tissues in finite domain is proposed to predict the control temperature profile
      at hyperthermia position. The treatment technique uses dual-phase-lag model of
      heat transfer in multilayer tissues with modified Gaussian distribution heat
      source subjected to the most generalized boundary condition and interface at the
      adjacent layers. The complete dual-phase-lag model of bioheat transfer is solved
      using finite element Legendre wavelet Galerkin approach. The present solution has
      been verified with exact solution in a specific case and provides a good
      accuracy. The effect of the variability of different parameters such as lagging
      times, external heat source, metabolic heat source and the most generalized
      boundary condition on temperature profile in multilayer tissues is analyzed and
      also discussed the effective approach of hyperthermia treatment. Furthermore, we
      studied the modified thermal damage model with regeneration of healthy tissues as
      well. For viewpoint of thermal damage, the least thermal damage has been observed
      in boundary condition of second kind. The article concludes with a discussion of
      better opportunities for future clinical application of hyperthermia treatment.

PMID- 27888932
TI  - Numerical study of non-Fourier heat conduction in a biolayer spherical living
      tissue during hyperthermia.
AB  - Laser interstitial thermal therapy is one of the best methods for tumor
      treatment. Quality of treatment is highly influenced by the way of temperature
      control that depends strongly upon the living tissue thermal properties. One
      dimensional dual-phase-lag (DPL) in spherical coordinate system numerically has
      been investigated for bioheat transfer during laser treatment in living
      biological tissues, which contain tumoral and normal layers. Various behaviors of
      heat transfer models such as wave, wavelike and diffusion are studied by
      adjusting the relaxation parameters. Effect of different phase lags values of the
      heat flux and the temperature gradient and thermal diffusivity on the behavior of
      heat transfer overshooting phenomenon is also investigated as well. Results
      indicate variation of the time lag and the thermal diffusivity of the normal and
      tumoral tissues. Also it has cleared that the geometrical conditions have
      significant effects upon the thermal response and overshooting phenomenon in
      biological tissue.

PMID- 27888933
TI  - Review on modeling heat transfer and thermoregulatory responses in human body.
AB  - Several mathematical models of human thermoregulation have been developed,
      contributing to a deep understanding of thermal responses in different thermal
      conditions and applications. In these models, the human body is represented by
      two interacting systems of thermoregulation: the controlling active system and
      the controlled passive system. This paper reviews the recent research of human
      thermoregulation models. The accuracy and scope of the thermal models are
      improved, for the consideration of individual differences, integration to
      clothing models, exposure to cold and hot conditions, and the changes of
      physiological responses for the elders. The experimental validated methods for
      human subjects and manikin are compared. The coupled method is provided for the
      manikin, controlled by the thermal model as an active system. Computational Fluid
      Dynamics (CFD) is also used along with the manikin or/and the thermal model, to
      evaluate the thermal responses of human body in various applications, such as
      evaluation of thermal comfort to increase the energy efficiency, prediction of
      tolerance limits and thermal acceptability exposed to hostile environments,
      indoor air quality assessment in the car and aerospace industry, and design
      protective equipment to improve function of the human activities.

PMID- 27888934
TI  - Thermoelastic modelling of the skin at finite deformations.
AB  - The modelling and computation of the coupled thermal and mechanical response of
      human skin at finite deformations is considered. The model extends current
      thermal models to account for thermally- and mechanically-induced deformations.
      Details of the solution of the highly nonlinear system of governing equations
      using the finite element method are presented. A representative numerical example
      illustrates the importance of considering the coupled response for the problem of
      a rigid, hot indenter in contact with the skin.

PMID- 27888936
TI  - Finite element model to study temperature distribution in skin and deep tissues
      of human limbs.
AB  - The temperature of body tissues is viewed as an indicator of tissue response in
      clinical applications since ancient times. The tissue temperature depends on
      various physical and physiological parameters like blood flow, metabolic heat
      generation, thermal conductivity of tissues, shape and size of organs etc. In
      this paper a finite element model has been proposed to study temperature
      distribution in skin and deep tissues of human limbs. The geometry of human limb
      is taken as elliptical tapered shape. It is assumed that outer surface of the
      limb is exposed to the environment. The appropriate boundary conditions have been
      framed based on physical conditions of the problem. The model has been developed
      for a three dimensional steady state case. Hexahedral circular sectoral elements
      are used to discretize the region. The results have been computed to obtain
      temperature profiles and study the relation of tissue temperature with the
      parameters like atmospheric temperature, rate of evaporation, thickness of
      tissues layers and shape of the limb.

PMID- 27888935
TI  - Modeling bioheat transfer processes and thermoregulatory responses.

PMID- 27888937
TI  - Patient- and Family-Centered Care: Why Radiology?

PMID- 27888938
TI  - Who We Are.

PMID- 27888939
TI  - Patient- and Family-Centered Care: A Primer.
AB  - Patient- and family-centered care is a model of providing care in which the
      patient and family are partners with the provider and care team. A resurgence of
      interest in patient- and family-centered care is due, in part, to increasing
      consumerism in health care and the linking of reimbursement to the patient
      experience. Individual radiologists, practices, enterprises, and radiology
      professional societies have been engaged with patient- and family-centered care
      in varying degrees for many years. Understanding the roots and evolution of this
      care model will encourage further application of these principles in radiology.

PMID- 27888940
TI  - Using Quality Improvement Methods to Improve Patient Experience.
AB  - Patient experience is an important component of the overall medical encounter.
      This paper explores how patient experience is measured and its role in radiology,
      including its impact on clinical outcomes and reimbursement. Although typically
      applied to safety and clinical outcomes, quality improvement methodology can also
      be used to drive improvement efforts centered on patient experience. Applying an
      established framework for patient-centered care to radiology, this paper provides
      a number of examples of projects that are likely to yield significant improvement
      in patient satisfaction measures.

PMID- 27888941
TI  - Lessons Learned From Two Decades of Patient- and Family-Centered Care in
      Radiology, Part 1: Getting Started.
AB  - Patient- and family-centered care has a long history, but the application of
      these principles to radiology is limited by infrequent direct patient contact for
      many radiologists; scarce peer-reviewed data in the radiology literature; and
      sparse access to implementation strategies, tools, and best practices. In a
      series of two articles, the authors share two decades of lessons learned from
      implementing patient- and family-centered care in a radiology department.

PMID- 27888942
TI  - Lessons Learned From Two Decades of Patient- and Family-Centered Care in
      Radiology, Part 2: Building a Culture.
AB  - As reimbursements are increasingly linked to patient experience, physicians and
      hospitals will need to find ways to incorporate patient and family input into
      operational decisions. Rather than starting from the beginning, health systems
      could learn from practitioners who have been experimenting in this space and are
      willing to share their experience. The authors share lessons learned from two
      decades of experience incorporating patient and family advisers into the clinical
      operation of a radiology department and the resulting culture change. Radiology
      and radiologists can incorporate principles of patient- and family-centered care
      into clinical operations without loss of productivity.

PMID- 27888943
TI  - Promising Approaches From Behavioral Economics to Improve Patient Lung Cancer
      Screening Decisions.
AB  - Lung cancer is a devastating disease, the deadliest form of cancer in the world
      and in the United States. As a consequence of CMS's determination to provide low
      dose CT (LDCT) as a covered service for at-risk smokers, LDCT lung cancer
      screening is now a covered service for many at-risk patients that first requires
      counseling and shared clinical decision making, including discussions of the
      risks and benefits of LDCT screening. However, shared decision making
      fundamentally relies on the premise that with better information, patients will
      arrive at rational decisions that align with their preferences and values.
      Evidence from the field of behavioral economics offers many contrary viewpoints
      that take into account patient decision making biases and the role of the shared
      decision environment that can lead to flawed choices and that are particularly
      relevant to lung cancer screening and treatment. This article discusses some of
      the most relevant biases, and suggests incorporating such knowledge into
      screening and treatment guidelines and shared decision making best practices to
      increase the likelihood that such efforts will produce their desired objectives
      to improve survival and quality of life.

PMID- 27888944
TI  - Focusing on the "Person" in Personalized Medicine: The Future of Patient-Centered
      Care in Radiation Oncology.
AB  - Numerous efforts in radiation oncology aim to improve the value of clinical care.
      To evaluate the success of these efforts, outcome measures must be well defined
      and incorporate the beliefs of the patients they affect. These outcomes have
      historically centered on rates of tumor control, overall survival, and adverse
      events as perceived and reported by providers. However, the future of patient
      centered care in radiation oncology is increasingly focusing on the "person" in
      the population and the individual in the studies to more closely reflect the
      ideals of personalized medicine. Formally known as patient-centered outcomes,
      this metric encompasses parameters of patient satisfaction, engagement, and
      treatment compliance. Evaluations that investigate the safety and efficacy of
      treatments are increasingly soliciting participation from patients within a model
      of shared decision making that improves patients' knowledge, satisfaction,
      physical and emotional well-being, and trust in providers. Modern clinical trials
      that embrace this approach may even focus on patient-reported outcomes as the
      primary end point, as opposed to time-honored physician-reported events. The
      authors explore the growing role of patient-centered care, the incorporation of
      shared decision making, and the relevant body of existing and developing
      literature on this topic in radiation oncology. The authors report recent
      discoveries from this area of study and describe how they can not only support
      high-quality, high-value patient care but also enhance recruitment to clinical
      oncology trials, both of which are challenging to achieve in today's relatively
      resource-strapped environment.

PMID- 27888946
TI  - Difficult Doctors, Difficult Patients: Building Empathy.
AB  - Effective doctor-patient communication facilitates the therapeutic relationship,
      promotes patient physical and mental health, and improves physician satisfaction.
      Methods of teaching effective communication use a range of techniques, typically
      combining didactic instruction with simulated communication encounters and
      reflective discussion. Rarely are patients and physicians exposed to these
      instructions as colearners. The evidence for the utility of graphic stories,
      comics, and cartoons to improve patient comprehension and self-regulation is
      small but encouraging. The authors describe the use of graphic medicine as a
      teaching tool for engendering empathy from both the physician and the patient for
      the other during a shared clinical encounter. This use of educational comics in a
      colearning experience represents a new use of the medium as a teaching tool.

PMID- 27888945
TI  - Radiology as the Point of Cancer Patient and Care Team Engagement: Applying the
      4R Model at a Patient's Breast Cancer Care Initiation.
AB  - Radiologists aspire to improve patient experience and engagement, as part of the
      Triple Aim of health reform. Patient engagement requires active partnerships
      among health providers and patients, and rigorous teamwork provides a mechanism
      for this. Patient and care team engagement are crucial at the time of cancer
      diagnosis and care initiation but are complicated by the necessity to orchestrate
      many interdependent consultations and care events in a short time. Radiology
      often serves as the patient entry point into the cancer care system, especially
      for breast cancer. It is uniquely positioned to play the value-adding role of
      facilitating patient and team engagement during cancer care initiation. The 4R
      approach (Right Information and Right Care to the Right Patient at the Right
      Time), previously proposed for optimizing teamwork and care delivery during
      cancer treatment, could be applied at the time of diagnosis. The 4R approach
      considers care for every patient with cancer as a project, using project
      management to plan and manage care interdependencies, assign clear
      responsibilities, and designate a quarterback function. The authors propose that
      radiology assume the quarterback function during breast cancer care initiation,
      developing the care initiation sequence, as a project care plan for newly
      diagnosed patients, and engaging patients and their care teams in timely,
      coordinated activities. After initial consultations and treatment plan
      development, the quarterback function is transitioned to surgery or medical
      oncology. This model provides radiologists with opportunities to offer value
      added services and solidifies radiology's relevance in the evolving health care
      environment. To implement 4R at cancer care initiation, it will be necessary to
      change the radiology practice model to incorporate patient interaction and
      teamwork, develop 4R content and local adaption approaches, and enrich radiology
      training with relevant clinical knowledge, patient interaction competence, and
      teamwork skill set.

PMID- 27888947
TI  - An Asynchronous Online Collaboration Between Radiologists and Patients:
      Harnessing the Power of Informatics to Design the Ideal Patient Portal.

PMID- 27888948
TI  - Web Applications for Patient Communication.
AB  - Communication between imaging professionals and patients can help achieve many
      goals, including improved patient understanding of imaging-related diagnostic and
      treatment options, better compliance with appropriate imaging screening
      procedures, and improved efficiency of service. The explosive growth of out-of
      pocket consumer spending on health care has heightened health care shopping, thus
      making patient communication an important goal of any imaging practice or health
      care organization. Furthermore, the Merit-Based Incentive Payment System
      introduced by CMS will publicly disclose physicians' quality ratings, which are
      in part dependent on patient engagement. The authors summarize the rationale for
      web communication with patients, the range of content that should be considered,
      and the technology options. The aim is to help imaging providers develop
      organized patient communication strategic and implementation plans.

PMID- 27888949
TI  - Implications of Direct Patient Online Access to Radiology Reports Through Patient
      Web Portals.
AB  - In an era of increasing health information transparency and informed decision
      making, more patients are being provided with direct online access to their
      medical records, including radiology reports, via web-based portals. Although
      radiologists' narrative reports have previously been the purview of referring
      physicians, patients are now reading these on their own. Many potential benefits
      may result from patients reviewing their radiology reports, including
      improvements in patients' own understanding of their health, promotion of shared
      decision making and patient-physician communication, and, ultimately,
      improvements in patient outcomes. However, there may also be negative
      consequences, including confusion and anxiety among patients and longer patient
      physician interactions. The rapid adoption of this new technology has led to
      major questions regarding ethics and professionalism for radiologists, including
      the following: Who is the intended audience of radiology reports? How should
      content be presented or worded? How will open access influence radiologists'
      relationships with patients and referring physicians? What legal ramifications
      may arise from increased patient access? The authors describe the current
      practices and research findings associated with patient online access to medical
      records, including radiology reports, and discuss several implications of this
      growing trend for the radiology profession.

PMID- 27888951
TI  - Patient and Family Engagement in Research in Era 3.

PMID- 27888950
TI  - Social Media and the Patient Experience.
AB  - As patients continue to turn to online resources for health care information to
      guide their care decisions, it is becoming increasingly important for
      radiologists to engage with patients online via social media platforms. There are
      many ways physicians can use social media to provide patients with valuable
      information and improve the overall patient experience. By optimizing online
      discoverability, curating radiology content, engaging with patient communities,
      and producing mineable social media content, radiologists can emerge as thought
      leaders in this new form of patient-centered communication and information
      exchange.

PMID- 27888952
TI  - A Tale of Two Perspectives on Cancer: What I Wish I Knew Before Cancer
      Radiologist and Patient Perspectives.

PMID- 27888953
TI  - Moral and Ethical Issues in Mental Health.

PMID- 27888954
TI  - The Effect of Internalized Stigma on the Self Esteem in Patients with
      Schizophrenia.
AB  - AIM: This study has been conducted to determine the relationship between
      internalized stigma and self-esteem in patients with schizophrenia. MATERIALS AND
      METHODS: This study was conducted using 60 patients with schizophrenia who were
      diagnosed as schizophrenic according to the DSM-IV diagnostic criteria in the
      psychiatric clinics of hospitals in Erzurum. The data were collected using the
      "Questionnaire on Internalized Stigma of Mental Illness Scale" (ISMI) that
      determines the socio-demographic characteristics of patients, and the "Short Form
      of Self-Esteem Scale" (SF-SES). RESULTS: The mean Internalized Stigma of Mental
      Illness Scale score was high; the mean of the positive dimension of the self
      esteem scale score was lower than negative dimension. A negative significant
      relationship was found (r=-.758, p<0.01) between the ISMI and SF-SES when we
      examined the relationship between the mean scores of self-esteem and internalized
      stigma levels of the patients. There is a significantly positive relationship
      between the mean scores of the stigma resistance and SERS-SF (r=.339, p<0.01).
      CONCLUSION: The findings show that the patients' self-esteem decreases with the
      increasing levels of internalized stigma. In particular, the high level of
      accepting stereotyped judgments and the low stigma resistance can be associated
      with low self-esteem. Based on these results, increasing psychoeducation and
      counseling services for patients with schizophrenia, and increasing the public
      awareness of this issue are recommended. Advanced quantitative studies should be
      conducted to determine the factors related to fighting stigma.

PMID- 27888955
TI  - Emotion Dysregulation Mediates Between Childhood Emotional Abuse and Motives for
      Substance Use.
AB  - The purpose of this study is to assess the relative mediating effects of
      impulsivity and emotion dysregulation in the relationship between childhood
      maltreatment and motives for opiate use. Seventy four adolescent users of
      Tramadol, a synthetic opiate, were recruited from a boot camp for de-addiction
      and rehabilitation services for the study. Data were collected between May, 2014
      and November, 2014. Participants completed assessments of childhood abuse
      history, difficulties regulating emotions, impulsiveness and motives for
      substance use as well as a socio-demographic information sheet. The results of
      the current study indicate that types of abuse may be associated with particular
      outcomes and can inform treatment planning for substance users. Findings from
      bootstrap mediator analyses indicated that emotion dysregulation, but not
      impulsiveness, mediated the relationship between childhood emotional abuse and
      expansion and enhancement motives for substance use. The current study provides
      preliminary evidence that difficulties regulating emotions may function as a
      mechanism linking prior childhood experiences of emotional abuse to subsequent
      motives for substance use. Clinical implications of these findings suggest that
      targeting emotion dysregulation problems may be an effective adjunct in the
      treatment of childhood emotional abuse adolescent victims at risk for substance
      use.

PMID- 27888956
TI  - Improving Adherence in Hospitalized Patients Diagnosed With Schizophrenia: An
      Integrative One-on-One Intervention.
AB  - OBJECTIVE: This study examined an individualized integrative nursing intervention
      for improving attitude and adherence. METHODS: The sample included 60 patients,
      randomly assigned to an experimental or control group. Measures included The
      Visual Analog Scale for Assessing Treatment Compliance and the Drug Attitude
      Inventory (DAI- 10). RESULTS: Significant differences were found in attitude and
      reported adherence for the experimental group, before and after. Significant
      differences were found between the experimental and control group in the degree
      of change in attitude and reported adherence. CONCLUSIONS: This study indicates
      the benefit of integrative one-on-one tailor-made intervention versus routine
      care for improving attitude and adherence to drug therapy.

PMID- 27888958
TI  - Improving Metabolic Syndrome Screening on Patients on Second Generation
      Antipsychotic Medication.
AB  - AIM: This quality improvement project aims at stressing the importance of
      screening for metabolic syndrome (MS) on patients with serious mental illness
      (SMI) managed with second generation antipsychotic (SGA) medication. METHOD: One
      hundred charts of patients who were on SGA (n=100) were randomly selected from
      more than 1000 charts for the purpose of this project with (n=50) charts for pre
      intervention and (n=50) charts for post intervention. A chi-square test of
      independence was calculated comparing the frequency of labs and vital done in pre
      intervention and post-intervention period. RESULTS: A significant interaction was
      found [chi2(2)=32.67, p<.001] indicating that providers were more likely to order
      labs in postintervention (62%) than in pre-intervention (22%). No significant
      relationship was found for vital signs [chi2(1)=.542, p>.05]. The use of the
      screening and monitoring tool showed that gaps exist in the screening for MS
      among patients on SGA. IMPLICATION TO PRACTICE: Advanced health nurse
      practitioners are well placed to take the lead in screening, monitoring, and
      implementing the necessary measures to address MS among patients with serious
      mental illness.

PMID- 27888957
TI  - An Online Mental Health and Wellness Intervention Supplementing Standard Care of
      Depression and Anxiety.
AB  - Online interventions offer benefits, but often have not been tested in studies.
      The aim was to study feasibility, acceptability, and preliminary effectiveness of
      an online intervention supplementing standard care of depression and anxiety. The
      study was conducted within a large healthcare system. Three primary care and four
      behavioral health providers recruited 96 participants. Overall, 91% (n=87) agreed
      to participate, while 43% (n=41) completed registration and 27% (n=26) logged
      into the intervention multiple times. Participants referred by behavioral health
      demonstrated greater involvement. Reductions in depression and anxiety were
      observed. Most providers were satisfied with the intervention. This study
      supports future research.

PMID- 27888959
TI  - Bearing Witness: The Lived Experience of Sitting With Patients.
AB  - There is abundant literature focused on the practice of using hospital sitters as
      part of standard patient safety care. However, minimal attention has been paid to
      understanding the actual experiences of hospital workers as they sit with
      distressed and often agitated patients. With the overwhelming number of
      hospitalized patients who require sitters, attention must be paid to the
      healthcare workers' perspective. In this study a phenomenological approach was
      used to elicit the perceptions of these hospital sitters. Themes which emerged
      from the participant's lived experiences of sitting included: Accepting them,
      It's not about me, You're not alone, Taking it to heart, Lifts me up, and
      Supporting role, with an overarching focus of Bearing witness. Nursing
      implications for this study suggest that using advanced practice psychiatric
      nurses in med-surg settings may help to support the hiring and training of
      skilled sitters and lead to improved psychological nursing care. In addition,
      identifying health care workers who best "fit" the sitter profile may promote the
      role from one of safety surveillance to one of therapeutic engagement.

PMID- 27888960
TI  - Wards in Opinion of Patients - A Comparative Study on the Quality of Nursing
      Care.
AB  - AIM: The aim of this study was to evaluate the quality of nursing care in
      psychiatric wards and compare it between hospitals of different types. RESULTS:
      Significant differences between hospitals were found in: personnel benevolence
      (p=0,006219) and response to patient needs (p=0,011446) as well as patients'
      sense of safety (p=0,020042). In both hospitals, patients were equally
      dissatisfied with the quality of information concerning treatment side effects
      (p=0,207804). In both hospitals patients were equally satisfied regarding the
      level of respect for their dignity and psychological support (p=0,176928).
      CONCLUSION: General patient perception of nursing care in psychiatry wards seems
      to be positive. Some tasks carried out by nurses in psychiatric care still
      require improvement, especially regarding providing information to patients.

PMID- 27888961
TI  - Facilitating Social Integration for People With Severe Mental Illness Served by
      Assertive Community Treatment.
AB  - PURPOSE: This article explores the experience of workers on Assertive Community
      Treatment (ACT) teams surrounding their efforts to facilitate social integration
      for their clients. DESIGN AND METHODS: Sixteen workers were individually
      interviewed and eight additional workers participated in two focus groups.
      FINDINGS: The formation of caring relationships between worker and client was an
      important first step towards social integration for ACT clients. Community
      activities offer opportunities for social interaction. PRACTICE IMPLICATIONS: The
      frequency of community based activities should be increased. Social integration
      should be a targeted focus of service by structurally embedding a social
      integration specialist onto the ACT model.

PMID- 27888962
TI  - Involuntary Hospitalization of Patients With Mental Disorders: Knowledge of
      Health Professionals.
AB  - A descriptive and exploratory study with a qualitative approach was undertaken to
      describe the knowledge of health professionals at a psychiatric hospital about
      involuntary hospitalization. Health professionals from the admission ward of a
      psychiatric hospital located in an inner city of the state of Sao Paulo, Brazil,
      participated in the study. Data were collected through semistructured interviews
      with sixteen health professionals and the analysis was based on thematic
      analysis. The professionals' lack of knowledge about involuntary hospitalizations
      was evidenced, including unfamiliarity with the modalities of psychiatric
      hospitalization, confusion to understand involuntary and compulsory
      hospitalization as well as the role of the public prosecutor in these cases. In
      that sense, the study participants' lack of knowledge and, on the other hand, the
      inertia of the public prosecutor's office can hamper the full enjoyment of rights
      by persons with mental disorders. In this scenario, psychiatric health
      professionals should know and understand the legislation as well their
      responsibility according to it, combining political with theoretical-technical
      knowledge.

PMID- 27888963
TI  - The Effectiveness of Structured Supported Education Programs for Families With
      Intellectually Disabled Children: The Example of Turkey.
AB  - This a quasi-experimental study that was conducted at a specialized education
      school in a city in Turkey for the purpose of evaluating the effectiveness of a
      structured supported education program for the parents of children with
      intellectual disability (ID). The education program was conducted with a total of
      8 groups attending 3 sessions. 104 individuals completing the program sessions
      and comprised the sample. In a comparison of parents' levels of knowledge, the
      mean number of correct answers on the pretest was 15+/-3.75 and 19.25+/-2.88 on
      the posttest. Beck hopelessnes scores were 9.75+/-4.14 before the education and
      6.25+/-4.77 after the education; this differences were statistically significant.
      It was found that the supported education of parents of individuals with ID made
      an impact on the family's knowledge and level of hopelessness.

PMID- 27888964
TI  - Stigma as a Structural Power in Mental Health Care Reform: An Ethnographic Study
      Among Mental Health Care Professionals in Belgium.
AB  - The growing interest among scholars and professionals in mental health stigma is
      closely related to different mental health care reforms. This article explores
      professionals' perceptions of the dehospitalization movement in the Belgian
      context, paying particular attention to the meaning of stigma. Combined
      participant observation and semi-structured interviews were used to both assess
      and contextualize the perceptions of 43 professionals. The findings suggest that
      stigma may function as a structural barrier to professionals' positive evaluation
      of de-hospitalization, depending on the framework they are working in. It is
      important to move beyond a unilateral understanding of the relationship between
      stigma and de-hospitalization in order to attain constructive health care reform.

PMID- 27888966
TI  - Implementation of a Recovery-Oriented Training Program for Psychiatric Nurses in
      the Inpatient Setting: A Mixed-Methods Hospital Quality Improvement Study.
AB  - This mixed-methods hospital quality improvement (QI) study primarily aimed to
      reduce the use of mechanical restraints in a short-stay inpatient psychiatric
      setting by facilitating change in care delivery through recovery-oriented nursing
      practice. The implementation of an evidence-based education for psychiatric
      mental health registered nurses (PMH-RNs) intended to improve their knowledge of,
      and attitudes toward, recovery-focused mental health treatment principles.
      Findings suggest that recovery-oriented training programs for PMH-RNs can be a
      potentially useful hospital strategy for restraint reduction. In this article,
      the authors report their findings using the SQUIRE 2.0 framework for publication
      of QI studies (Ogrinc et al., 2015).

PMID- 27888965
TI  - Effects of Nursing Interventions on Depression of Patients With Rheumatoid
      Arthritis: A Meta-Analysis of Randomized Controlled Trials.
AB  - INTRODUCTION: Previous randomized controlled trials have led to conflicting
      findings regarding the effects of nursing interventions on depression of patients
      with rheumatoid arthritis (RA). The purpose of this study was to use the meta
      analytic approach to resolve these discrepancies. METHODS: We performed a
      systematic search of publications using MEDLINE, EMBASE, the Cochrane Library,
      and manual searches without language restrictions. Studies that met the following
      criteria were included: (1) randomized controlled trials; (2) duration of
      intervention>=4 weeks; (3) comparative control group; (4) adults with RA; (5)
      published studies in any language since reception; and (6) psychological symptoms
      assessed. We extracted relative risks (RRs) and 95% confidence internals (CIs)
      and pooled them using a random effect model. We carried out sensitivity analysis
      and assessed heterogeneity and publication bias. RESULTS: A total of 14 studies,
      including 1803 patients, were eligible for inclusion in the review. Depression
      symptom was assessed by questionnaires. In the pooled analysis, nursing
      interventions, including exercise training, medication guide, health education
      and psychotherapy were associated with the remission of depression (RR: -0.67;
      95% CI: -0.89 to -0.46; P<0.01) with significant heterogeneity between studies
      (P<0.01). CONCLUSION: Nursing interventions may be important adjunctive therapies
      in the medical management of RA patients.

PMID- 27888967
TI  - Effects of Aggression Replacement Training on Problem Solving, Anger and
      Aggressive Behaviour among Adolescents with Criminal Attempts in Turkey: A Quasi
      Experimental Study.
AB  - The research was conducted by a pretest and post-test conducted in a quasi
      experimental design which aimed to determine effectiveness of Aggression
      Replacement Training (ART) on problem solving, anger and aggressive behaviour
      among adolescents with criminal attempts in Turkey. The study included 65
      adolescents with criminal attempts (32 intervention, 33 control). There was no
      difference between the groups in terms of average age (16.13+/-1.10 in the
      experimental group and 16.21+/-0.89 in the control group). After the
      intervention, the experimental group showed significantly decreased Trait Anger
      levels (t=1.906; P=0.033), increased Anger Control scores (t=2.522; P=0.008),
      decreased Physical Aggression scores (t=1.925; P=0.031), decreased Hostility
      scores (t=2.496; P=0.009), increased Social Problem Solving total scores
      (t=2.937; P=0.005). Increased Anger Control scores were found to be significant
      when compared with the control group (t=2.273, P=0.026). These results showed
      that ART was effective on problem solving, anger and aggressive behaviour and can
      be used to develop positive behaviours among adolescents with criminal attempts.

PMID- 27888968
TI  - Predictors of Depression among Seropositive Batswana Men and Women: A Descriptive
      Correlational Study.
AB  - The purpose of this descriptive correlational study was to describe predictors of
      depressive symptoms among N=70 seropositive Botswana men and women residing in
      Gaborne, Botswana. A demographic questionnaire, the Center for Epidemiologic
      Studies Depression Scale, (CESD-D), and the SF-36 [Quality of life] were
      administered. The questionnaires were translated and back translated in Setswana
      and administered by Batswana men and women. The results of the regression
      analyses resulted in two calculated models. In the first Model energy/fatigue
      explained 46% of the variance in depressive symptoms (P=.000), and in the second
      Model energy/fatigue and role limitations on emotional well-being explained 50%
      of the variance in depressive symptoms respectively. The study findings
      underscore the need for mental health services for seropositive Batswana men and
      women.

PMID- 27888969
TI  - Smoking Behaviors and Medical Co-Morbidities in Patients With Mental Illnesses.
AB  - Correlations among smoking behaviors and co-morbid medical illnesses were
      examined among 982 smokers with mental illnesses enrolled in a smoking cessation
      program within Mental Health and Addictions Services in Vancouver, Canada.
      Significant correlates among individuals with psychotic disorders included
      associations between a history of emphysema/chronic obstructive pulmonary (COPD)
      disease and cigarettes smoked per day (r's=.35, p<=.01), Confidence in quitting
      (r's=-.33, p<=.01), and nicotine dependence (r's=.32, p<=.01). Study findings may
      have implications for the development of integrated medical-psychiatric treatment
      delivery models that include comprehensive tobacco cessation programs tailored
      toward people with mental illnesses.

PMID- 27888970
TI  - Paternal Depression Rates in Prenatal and Postpartum Periods and Affecting
      Factors.
AB  - The objective of this study was to determine the paternal depression rates and
      affecting factors in prenatal and postpartum periods. The study, which was
      descriptive and cross-sectional, was conducted with 92 volunteer couples that
      suited the criteria for the sample. These participants were selected from couples
      that applied to the gynecology clinic of a private hospital between September
      2014 and April 2015 and who were in their 37th-40th weeks of pregnancy. Data
      collection was planned in two interviews; the first one was done between the 37th
      and 40th weeks of the pregnancy, and the second was conducted between the 4th and
      6th weeks after the birth. Interviews were completed with 84 couples. In this
      study, it was determined that there was no relationship between average paternal
      and maternal scores on the Edinburgh Postnatal Depression Scale (EPDS) in
      prenatal and postpartum periods. It was found that the average score of the
      Family-Work Conflict Scale increased and couples' marriage harmony decreased as
      the EPDS average score for fathers increased. In addition, it was found that the
      EPDS average score for fathers that wanted the pregnancy was less compared to
      fathers that did not want the pregnancy, and the difference between the two
      groups was statistically meaningful.

PMID- 27888971
TI  - U.S. Caregivers with Mental Health Problems: Parenting Experiences and Children's
      Functioning.
AB  - The 2007 National Survey of Children's Health was used to determine the
      prevalence of poor mental health among U.S. mothers, fathers, and guardians,
      specific parenting experiences and children's functioning. More guardians (13.7%)
      reported poor mental health compared to mothers (7.7%) and fathers (5.3%),
      generalizing to 4.6 million U.S. caregivers with poor mental health. Caregivers
      with poor mental health were at least 3 times more likely to report children's
      problematic functioning after accounting for sociodemographic factors and
      parenting stress and experiences. Research and clinical activities should
      recognize poor caregiver mental health as a condition that affects parenting and
      children's functioning.

PMID- 27888972
TI  - The Effect of Yoga on Functional Recovery Level in Schizophrenic Patients.
AB  - PURPOSE: The objective of this study is to determine the effect of yoga on
      functional recovery level in schizophrenic patients. MATERIALS AND METHODS: The
      study was conducted in quasi-experimental design with pretest-posttest control
      group. The population of the study consisted of schizophrenic patients with
      registered in Malatya and Elazig Community Mental Health Centers and regularly
      going to these centers. The sample group of the study consisted of totally 100
      patients including 50 patients in the experimental group and 50 patients in the
      control group who were specified through power analysis and chosen by using
      random sampling method from this population. The data were collected between
      April 2015 and August 2015. 'Patient Description Form' and 'FROGS' were used to
      collect the data. Yoga was applied to patients in the experimental group. Any
      intervention was not made to patients in the control group. Percentage
      distribution, arithmetic mean, standard deviation, chi-square, independent
      samples t test, and paired t test were used to assess the data. RESULTS: Patients
      in the control and experimental group pretest subscale and the total means scores
      of FROGS was found to be low. In the posttest subscale and total means scores of
      FROGS in the experimental group were higher than in the control group and the
      differences between them were found to be statistically significant (p<0.05). In
      the experimental group pretest and posttest subscale and total means scores of
      FR0GS was determined to be statistically significant (p<0.05). CONCLUSION: Yoga
      that applied to schizophrenic patients it was determined to increased the level
      of functional recovery. It can be suggested that yoga should be used as an
      complementary method in nursing practise in order to increase the effectiveness
      of the treatment.

PMID- 27888973
TI  - Comparison of Caregiver Burden in First Episode Versus Chronic Psychosis.
AB  - The aim of this study was to compare burden on caregivers of patients with first
      episode psychosis and caregivers of those with chronic psychosis. The study
      sample consisted of 39 caregivers of patients with first episode psychosis and 40
      caregivers of patients with chronic psychosis. The Caregiver Burden Inventory
      (CBI) was used for data collection. The average caregiver burden in caregivers of
      patients with chronic psychosis was significantly higher than that in caregivers
      of patients with first episode psychosis. With regard to the subscales of CBI,
      there was a significantly higher level of burden in terms of time dependence,
      development, physical burden, and social burden in caregivers of patients with
      chronic psychosis than in caregivers of patients with first episode psychosis,
      while no such difference could be detected for the emotional burden. The absence
      of a difference in emotional burden suggests that caregivers of first episode
      psychosis may be going through an intense emotional experience, placing them in a
      high-risk status, despite an average caregiving experience duration of 11 months.
      Family interventions targeting the caregivers of patients with chronic psychosis
      or patients with first episode psychosis should be planned in accordance with the
      specific needs of these caregiver groups. It is also recommended to conduct
      programs involving the concurrent participation of the caregivers of patients
      with first episode psychosis and caregivers of patients with chronic psychosis
      and interventional programs such as "early psychosis support" for the caregivers
      of patients with first episode psychosis.

PMID- 27888974
TI  - Early Intervention in Schizophrenia: A Literature Review.
AB  - Schizophrenia is a debilitating psychiatric disorder seen across the world.
      Recently, investigators have witnessed an upsurge in research on the potential
      benefits of early intervention during the prodromal stage: the sooner people
      start the treatment at their first psychotic episode, the better outcome on
      symptom relief and better functioning. This paper aims to critically review and
      synthesize empirical evidence published between 2005 and 2015 regarding the
      effectiveness of preemptive interventions on transition rate, symptom severity,
      depression, anxiety, and function level. Randomized controlled trials were
      identified in seven different electronic databases and twelve studies were
      included in this review. Findings indicated that intervention was designed not
      only for help-seeking individuals, but also for their family members. Also, the
      applications for psychiatric nursing are discussed.

PMID- 27888975
TI  - The Therapeutic Relationship in Inpatient Psychiatric Care: A Narrative Review of
      the Perspective of Nurses and Patients.
AB  - PURPOSE: To study the significance of 'therapeutic relationship' between nurses
      and patients within the context of a psychiatric hospital. METHOD: Narrative
      literature review. Content analysis. FINDINGS: The significance of the
      therapeutic relationship is quite similar for both nurses and patients in
      psychiatric hospital units. Nevertheless, several factors may separate the two
      positions: the time available for the relationship, the negative perceptions on
      the part of both parties, and the insecurity of the setting. PRACTICE
      IMPLICATIONS: Increased knowledge and understanding of the significance of the
      therapeutic relationship from the perspective of nurses and patients would allow
      the strengthening of areas of mutual interest.

PMID- 27888976
TI  - The Variability of Nursing Attitudes Toward Mental Illness: An Integrative
      Review.
AB  - Mental illnesses are common worldwide, and nurses' attitudes toward mental
      illness have an impact on the care they deliver. This integrative literature
      review focused on nurses' attitudes toward mental illness. Four databases were
      searched between January 1, 1995 to October 31, 2015 selecting studies, which met
      the following inclusion criteria: 1) English language; and 2) Research in which
      the measured outcome was nurses' attitudes toward mental illness. Fourteen
      studies conducted across 20 countries that 4282 participants met the inclusion
      criteria. No study was conducted in the United States (U.S.). Studies reported
      that nurses had mixed attitudes toward mental illness, which were comparable to
      those of the general public. More negative attitudes were directed toward persons
      with schizophrenia. Results indicate the need for further research to determine
      whether attitudes among nurses in the U.S. differ from those reported from other
      countries and to examine potential gaps in nursing curriculum regarding mental
      illness.

PMID- 27888977
TI  - Factors Affecting Medication Adherence Among Adults with Schizophrenia: A
      Literature Review.
AB  - This review aimed to summarize empirical evidence concerning factors relating to
      medication adherence among patients with schizophrenia. A comprehensive search
      was implemented to recruit articles which met the present eligibility criteria.
      Twenty-five articles were included whereby only one was a qualitative study.
      Greater awareness of illness (insight), previous history of medication adherence,
      positive attitude toward medication, types of atypical antipsychotics, less
      severe psychotic symptoms, and social support were identified as factors of
      medication adherence. Knowledge gaps and methodological limitations were also
      identified. Implications to clinical practice include providing psychoeducation
      to patients by increasing their knowledge about illness and medication.

PMID- 27888978
TI  - Vulnerability, Stress, and Support in the Disease Trajectory from Prodrome to
      Diagnosed Schizophrenia: Diathesis-Stress-Support Model.
AB  - Schizophrenia is a debilitating psychiatric disorder seen across the world. The
      goal of current research is to provide a more comprehensive understanding of
      prodrome, the initial period before the disease manifests as schizophrenia.
      Unfortunately, there is little information to comprehensively understand the
      indicators that later lead to schizophrenia. This has resulted in a lack of
      scientific knowledge to aid in early identification and intervention by
      psychiatric nurses or school nurses. Such information could inform nursing
      assessment and care plan development. The purpose of this paper is to construct a
      conceptual model for describing the important factors relating to the
      schizophrenia prodrome process in human developmental manner by critically
      synthesizing empirical evidence and reviewing the strengths and limitations of
      current conceptual models.

PMID- 27888979
TI  - Corrigendum to "A Comparison of Suboxone and Clonidine Treatment Outcomes in
      Opiate Detoxification" [Archives of Psychiatric Nursing 26 (4) (2012):316-323].

PMID- 27888980
TI  - Noninvasive determination of renal tumor histology utilizing molecular imaging.

PMID- 27888981
TI  - Emerging role of immunotherapy in urothelial carcinoma-Advanced disease.
AB  - Systemic therapy for metastatic urothelial carcinoma has seen minimal progress
      and no new approved therapies in the past 20 years. However, with the approval of
      the checkpoint inhibitor atezolizumab in May 2016, immunotherapy inserted itself
      into the standard clinical dogma. The emergence of systemic immunotherapies,
      heralded by drugs targeting immune checkpoint blockade, can provide durable
      remissions in a subset of patients with a favorable toxicity profile. With other
      similar agents showing promise in early-phase trials, more options may be on the
      way. Current and ongoing trials are investigating ways to increase response rates
      with rational combinations as well as to uncover predictive biomarkers to
      identify patients most likely to benefit. In this review, we present updated data
      regarding immunotherapeutic agents in clinical trials as well as ongoing studies
      investigating novel designs, intriguing combinations, and alternative
      immunotherapy strategies.

PMID- 27888982
TI  - Contraceptive choices and preferences in a cohort of women with cystic fibrosis.
AB  - OBJECTIVES: As life expectancy for women with cystic fibrosis (CF) improves,
      reproductive decision-making is becoming increasingly relevant. We sought to
      characterize fertility intentions, contraceptive use, and preferences among adult
      females with CF. STUDY DESIGN: We conducted a cross-sectional survey of
      contraceptive use and preferences in reproductive-aged women with CF. Subjects
      were recruited via an electronic mailing list from the Penn Adult Cystic Fibrosis
      Program. RESULTS: Fifty-three women with CF responded and met eligibility
      criteria. Most (83%) were sexually active, however only 49% used contraception.
      Condoms and the oral contraceptive pill were the most commonly used methods.
      Compared to the national contraceptive use among Caucasian women (65%), use in
      our cohort was significantly lower (p = 0.01). Participants prioritized
      effectiveness and ease of use in their contraceptive method; they wanted to avoid
      side effects and interference with sexual enjoyment. Although these priorities
      are similar to Caucasian women in the literature, additional contraceptive
      priorities differed significantly between the groups. CONCLUSIONS: This CF cohort
      is sexually active but contraceptive utilization was low, and women with CF
      identify specific contraceptive preferences. There is a significant unmet need
      for contraception among women with CF.

PMID- 27888983
TI  - High flow nasal cannula versus conventional oxygen therapy and non-invasive
      ventilation in adults with acute hypoxemic respiratory failure: A systematic
      review.
AB  - INTRODUCTION: Humidified oxygen via a high flow nasal cannula (HFNC) is a form of
      supplemental oxygen therapy that has significant theoretical advantages over
      conventional oxygen therapy (COT). However, the clinical role of HFNC in acute
      hypoxemic respiratory failure (AHRF) has not been well established. This review
      compares the efficacy of HFNC with COT and non-invasive ventilation (NIV) in
      patients with AHRF. METHODS: Studies reviewed were selected based on relevance
      from a systematic literature search conducted in Medline and EMBASE to include
      all published original research through May 2016. Twelve studies matched the
      inclusion criteria. RESULTS: In the majority of the studies, HFNC was associated
      with superior comfort and patient tolerance as compared to NIV or COT. HFNC was
      associated with reduced work of breathing in comparison with COT in some, but not
      all, studies in the review. COT and NIV were associated with a higher 90-day
      mortality rate compared to HFNC in only one multicenter randomized trial versus
      no mortality difference reported by others. Three out of four studies
      demonstrated a decreased need for escalation of oxygen therapy with HFNC. Six out
      of eight studies demonstrated improved oxygenation with HFNC as compared to COT.
      Two of three studies revealed worse oxygenation with HFNC as compared to NIV.
      CONCLUSION: This review suggests that HFNC may be superior to COT in AHRF
      patients in terms of oxygenation, patient comfort, and work of breathing. It may
      be reasonable to consider HFNC as an intermediate level of oxygen therapy between
      COT and NIV.

PMID- 27888984
TI  - Efficacy of a minimal home-based psychoeducative intervention in patients with
      advanced COPD: A randomised controlled trial.
AB  - BACKGROUND: Anxiety is a common comorbidity in patients with advanced Chronic
      Obstructive Pulmonary Disease (COPD) with major impact on quality of life and
      associated with increased risk of death. The objective of this randomised
      controlled trial was to test the efficacy of a minimal home-based psychoeducative
      intervention versus usual care for reducing symptoms of anxiety in patients with
      advanced COPD. METHODS: The trial included 66 participants with advanced COPD and
      symptoms of anxiety. The primary outcome was anxiety assessed by the Hospital
      Anxiety and Depression scale (HADS) subscale for anxiety (HADS-A). The secondary
      outcome was mastery assessed by the Chronic Respiratory Questionnaire (CRQ)
      domain of mastery (CRQ-M). Assessments were performed at baseline and one and
      three months post-intervention. RESULTS: The intervention group had a lower post
      intervention HADS-A score on average, compared with the control group (p =
      0.005), indicating a significant effect of the intervention. The average
      difference between the groups in HADS-A was 2.16 points (CI = [0.62; 3.71]) at
      one month and 2.32 points (CI = [0.74; 3.89]) at three months follow-up. The
      intervention group had a higher post intervention CRQ-M score on average compared
      with the control group (p = 0.016). The average differences between the groups
      were 0.58 points (CI = [0.09; 1.06]) after one month and 0.67 points (CI = [0.18;
      1.17]) after three months. CONCLUSIONS: The psychoeducative intervention provided
      sustainable symptom relief and improved the patients' self-management abilities.

PMID- 27888985
TI  - Azathioprine response in patients with fibrotic connective tissue disease
      associated interstitial lung disease.
AB  - BACKGROUND: Azathioprine is a commonly prescribed therapy for connective tissue
      disease-associated interstitial lung disease (CTD-ILD). Combination therapy that
      included azathioprine was recently shown to increase the risk of death and
      hospitalization in patients with idiopathic pulmonary fibrosis. Whether
      azathioprine increases the risk of adverse outcomes in patients with fibrotic CTD
      ILD, including those with CTD-associated usual interstitial pneumonia (UIP),
      remains unknown. METHODS: A retrospective cohort analysis was performed to
      determine the combined incidence rate of death, transplant and respiratory
      hospitalization associated with azathioprine exposure. A fibrotic CTD-ILD cohort
      treated with mycophenolate mofetil served as a comparator group. Incidence rates
      were compared with an incidence rate ratio (IRR) generated by negative binomial
      regression. Longitudinal pulmonary function response was then assessed using
      mixed effects linear regression models. RESULTS: Fifty-four patients were treated
      with azathioprine and forty-three with mycophenolate. Medication discontinuation
      due to non-respiratory side effects occurred in 27% and 5% of the azathioprine
      and mycophenolate cohorts, respectively. The combined incidence rate of adverse
      outcomes was 0.015 and 0.013 for azathioprine and mycophenolate, respectively
      (IRR 1.23; 95% CI 0.49-3.12; p = 0.66). Similar incidence rates were observed
      among those with CTD-UIP (IRR 0.83; 95% CI 0.21-3.31; p = 0.79). Both groups
      demonstrated pulmonary function stability over time, with the azathioprine group
      demonstrating a marginal improvement. CONCLUSIONS: A significant minority of
      patients could not tolerate azathioprine due to non-respiratory side effects. Of
      those who did tolerate azathioprine, a similar incidence of adverse outcomes was
      observed as those treated with mycophenolate. Both therapies were associated with
      stability in pulmonary function.

PMID- 27888986
TI  - Relationship between birth weight, maternal smoking during pregnancy and
      childhood and adolescent lung function: A path analysis.
AB  - BACKGROUND: Low birth weight and gestational maternal smoking have been linked
      with reduced lung function in children in many cross sectional studies. However,
      these associations have not yet been assessed with repeated measurements of lung
      function. Our aim was to investigate the effects of birth weight, gestational
      age, and gestational maternal smoking on lung function in children at age 10 and
      18 years. METHODS: In the Isle of Wight birth cohort spirometry was performed at
      age 10 and 18 years. Information on birth weight and gestational age were
      obtained from hospital records. Mothers were asked about smoking during
      pregnancy. We employed linear mixed models to estimate the effect of these risk
      factors on repeated measurements of lung function. We considered maternal asthma,
      sex, neonatal intensive care unit admission, height, socio-economic status,
      personal smoking in participants at age 18, body mass index and environmental
      tobacco smoke exposure as potential confounders. Finally, we used path analysis
      to determine links between birth weight, gestational age and gestational maternal
      smoking on lung function at age 10 and 18 years. RESULTS: Linear mixed models
      showed that with every 1 kg increase in birth weight, Forced expiratory volume in
      one second (FEV1) increased by 42.6 +/- 17.2 mL and Forced expiratory flow
      between 25% and 75% (FEF25-75) of Forced vital capacity (FVC) increased by 95.5
      +/- 41.2 mL at age 18 years after adjusting for potential confounders. Path
      analysis suggested that birth weight had positive direct effects on FEV1 and
      FEF25-75 and positive indirect effect on FVC at 10 years which were carried
      forward to 18 years. Additionally, results also suggested a positive association
      between gestational age and FEV1, FVC and FEF25-75 at ages 10 and 18 years and an
      inverse association between gestational smoke exposure and FEV1/FVC ratio and
      FEF25-75 at age 18 years. CONCLUSIONS: Higher birth weight and gestational age
      were associated with higher FEV1, FVC and FEF25-75 and maternal smoking during
      pregnancy was associated with reduced FEV1/FVC ratio and FEF25-75. The use of
      path analysis can improve our understanding of underlying "causal" pathways among
      different prenatal and childhood factors that affect lung function in both pre
      adolescent and adolescent periods.

PMID- 27888988
TI  - Prevalence and incidence of bronchiectasis in Catalonia, Spain: A population
      based study.
AB  - BACKGROUND: Insufficient epidemiological data are available on bronchiectasis in
      southern European populations. The aim of this study was to determine the
      prevalence and incidence of bronchiectasis in Catalonia, Spain and describe the
      characteristics of patients with an active diagnosis of bronchiectasis in 2012.
      METHODS: This study used data from a population database containing information
      from 5.8 million people (80% of the population of Catalonia). Patients with
      bronchiectasis were identified using International Statistical Classification of
      Diseases and Related Health Problems, 10th revision (ICD-10) codes, and
      information on clinical characteristics and treatment was extracted. RESULTS: A
      total of 20895 patients with bronchiectasis were identified in 2012. The
      prevalence of bronchiectasis was 36.2 cases per 10 000 inhabitants, with an
      incidence of 4.81 cases per 10 000 inhabitants. Prevalence and incidence
      increased with age and were highest in men over 65 years of age. Among the whole
      bronchiectasis population in Primary Care, 48.6% of patients had had blood tests,
      11.2% had undergone spirometry, only 2.1% had a chest X-ray, and 0.9% had
      undergone high-resolution computed tomography or sputum culture. 56% had at least
      one exacerbation and 12.5% had been admitted to hospital during the year of the
      study. The drugs most frequently used were inhaled corticosteroids (in 37.4% of
      patients) and long-acting beta2agonists (in 36%); half of the patients received
      no treatment (51.8%). CONCLUSIONS: The prevalence and incidence of bronchiectasis
      increases with age. The management of bronchiectasis in primary care was not
      optimal, and the disease continues to represent an important clinical burden.

PMID- 27888987
TI  - Free asthma medications reduces hospital admissions in Brazil (Free asthma drugs
      reduces hospitalizations in Brazil).
AB  - BACKGROUND: Since June 2011, the Brazilian health system started providing asthma
      medications (beclomethasone and salbutamol), totally free of charge to patients
      with asthma. The aim of this study was to evaluate the impact of the provision of
      free asthma medications on hospital admissions for asthma in Brazil, using a
      national hospitalization database (DATASUS), comparing the incidence of hospital
      admissions before and after the free supply of these drugs. METHODS: Admissions
      of patients with 1-49 years of age by the Brazilian public health system with the
      diagnosis of asthma were compared pre (2008-2010) and post (2012-2014) provision
      of free medicines (beclomethasone and salbutamol). The number of hospital
      admissions due to asthma and non-respiratory diseases, as well as the amount
      spent with asthma hospitalization, were obtained from DATASUS, the Brazilian
      government open-access public health database system. RESULTS: Admission rates
      for asthma significantly decreased from 90.09/100.000 (2008-2010) to
      59.85/100.000 (2012-2014), when the period pre and post provision of free
      medicines were compared [OR 0.67 (CI 0.48-0.92)]. Non-respiratory admission rates
      remained stable, when both periods were also compared. CONCLUSION: Asthma
      hospitalization rates significantly decreased in the three-year period after the
      provision of free medicines to treat asthma. Our findings suggest that the
      provision of free medications for asthma may have a particular public health
      impact by its own in developing countries.

PMID- 27888989
TI  - Burden and risk factors of ambulatory or hospitalized CAP: A population based
      cohort study.
AB  - BACKGROUND: Data on incidence, risk factors and outcome of community-acquired
      pneumonia (CAP) including outpatients is sparse. METHODS: We conducted a cohort
      study on 1.837.080 adults insured by a German statutory health insurance in 2010
      2011. CAP was identified via ICD-10-GM codes, ambulatory cases were validated by
      antibiotic prescription within 7 days. Primary outcomes were incidence,
      hospitalisation and 30-day all-cause mortality. Evaluated risk factors included
      age, sex and comorbidities. Evaluation was done by multivariate regression
      analysis adjusting for these factors and health care utilization. RESULTS: CAP
      incidence was 9.7 per 1000 person years, hospitalisation rate 46.5%, and 30-day
      mortality 12.9%. 30-day mortality of ambulatory cases was 5% (with 27%
      subsequently hospitalized for another diagnosis before death). 30-day mortality
      of hospitalized patients was 21.9%, but in-hospital mortality 17.2%. Risk factors
      for CAP included age, male sex and all evaluated comorbidities with highest risk
      for neurologic (OR 2.4), lung (OR 2.3) or immunosuppressive (OR 2.1) disease.
      Mortality risk was highest for neurologic (OR 2.3) and malignant (OR 2.0)
      disease. CONCLUSIONS: CAP constitutes a major burden in terms of incidence,
      morbidity and all-cause mortality in hospitalized and ambulatory patients.
      Interventions to raise awareness for disease impact also in ambulatory patients
      with risk factors are warranted.

PMID- 27888991
TI  - Pulmonary function and adverse cardiovascular outcomes: Can cardiac function
      explain the link?
AB  - BACKGROUND: The complex interaction between pulmonary function, cardiac function
      and adverse cardiovascular events has only been partially described. We sought to
      describe the association between pulmonary function with left heart structure and
      function, all-cause mortality and incident cardiovascular hospitalization.
      METHODS: This study is a retrospective analysis of patients evaluated in a single
      tertiary care medical center. We used multivariable linear regression analyses to
      examine the relationship between FVC and FEV1 with left ventricular ejection
      fraction (LVEF), left ventricular internal dimension in systole and diastole
      (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics,
      right ventricular function and lung hyperinflation. We also used Cox proportional
      hazards models to examine the relationship between FVC and FEV1 with all-cause
      mortality and cardiac hospitalization. RESULTS: A total of 1807 patients were
      included in this analysis with a median age of 61 years and 50% were female.
      Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals
      with FVC less than 2.75 L, decreased FVC was associated with increased all-cause
      mortality after adjusting for left and right heart echocardiographic variables
      (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was
      associated with increased cardiac hospitalization after adjusting for left heart
      size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75,
      95% CI 0.57, 0.97). CONCLUSION: In a tertiary care center reduced pulmonary
      function was associated with adverse cardiovascular events, a relationship that
      is not fully explained by left heart remodeling or right heart dysfunction.

PMID- 27888990
TI  - A randomized, controlled multicentric study of inhaled budesonide and intravenous
      methylprednisolone in the treatment on acute exacerbation of chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Almost all international guidelines recommend corticosteroids for
      management of exacerbations of chronic obstructive pulmonary disease (COPD),
      because it leads to improved outcomes of acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD). Nevertheless, due to its side effects,
      there are still concerns regarding the use of systemic corticosteroid (SC).
      Inhaled corticosteroids (IC) can be used as an alternative to SC, while reducing
      the risk of occurrence of side effects. PURPOSE: To measure the clinical efficacy
      and side effects of nebulized budesonide and systemic methylprednisolone in
      AECOPD. METHODS: Valid data from 410 AECOPD patients in 10 hospitals was
      collected. Patients were randomly divided into 2 groups; budesonide group,
      treated with nebulized budesonide (2 mg 3 times/day); and methylprednisolone
      group, treated with intravenously injected methylprednisolone (40 mg/day). COPD
      assessment test (CAT), arterial blood gas analysis, hospitalization days, adverse
      effects, fasting blood glucose, serum creatinine, alanine aminotransferase
      levels, and blood drug were measured and analyzed in both groups. RESULTS:
      Symptoms, pulmonary function and arterial blood gas analysis were significantly
      improved after treatment in both groups (P < 0.05), with no significant
      differences between them (P > 0.05), while incidence of adverse events in the
      budesonide group was lower (P < 0.05). No significant differences in CAT score,
      days of admission, blood gas analysis results and physiological and biochemical
      indexes were found between the two groups. Patients treated with
      methylprednisolone showed a higher degree of PaO2 level improvement. CONCLUSION:
      Results show that inhalation of budesonide (2 mg 3 times/day) and systemic
      methylprednisolone (40 mg/day) had similar clinical outcome in AECOPD. In
      conclusion, inhaled budesonide is an alternative to systemic corticosteroids in
      AECOPD treatment.

PMID- 27888992
TI  - IL-17 protein levels in both induced sputum and plasma are increased in stable
      but not acute asthma individuals with obesity.
AB  - BACKGROUND: Obesity worsens asthma control partly through enhanced airway
      neutrophilia, altered lung mechanics and comorbidities, including obstructive
      sleep apnea syndrome, gastroesophageal reflux disease and depression. Although
      controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is
      associated with neutrophilic inflammation, steroid resistance and severe asthma,
      but its importance in the association between asthma and obesity is unknown.
      OBJECTIVE: To investigate the role of IL-17 in obese asthma in both acute and
      stable settings. METHODS: Both stable (n = 177) and acute (n = 78) asthmatics
      were recruited and categorized into lean (n = 77 and 39 respectively), overweight
      (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and
      compared for clinical characteristics, including sputum and plasma IL-17 protein
      concentrations, sputum cellularity, spirometry and comorbidities. Correlations of
      IL-17 expression with other measures were explored. RESULTS: In stable subjects,
      airway neutrophilia and IL-17 concentrations were most prominent in the obese,
      and correlated positively with each other. Significant increase in plasma IL-17
      levels was also noted and associated with elevated depressive symptoms in
      obesity. In acute asthma, IL-17 expression, like most other clinical measures,
      was similar among lean, overweight and obese groups, but was higher in acute
      versus stable asthma subjects, with sputum IL-17 correlating positively with
      sputum neutrophils and negatively with FEV1 and plasma IL-17 showing a positive
      connection to airway eosinophilia during exacerbation. CONCLUSIONS: IL-17
      contributes to worse disease control in obese asthma through enhancing airway
      neutrophilia and depression, and may implicate in asthma exacerbations. Effects
      of adiposity on acute asthma remain uncertain.

PMID- 27888994
TI  - Early life exposure to traffic-related air pollution and allergic rhinitis in
      preschool children.
AB  - BACKGROUND: Evidence linking long-term exposure to outdoor air pollution with
      allergic rhinitis (AR) in children is scare, and the role of components of air
      pollution and timing of exposure remains unclear. OBJECTIVE: To assess the
      association of pre- and post-natal exposure to air pollution with life-time
      prevalence of AR in preschool children. METHODS: We conducted a cohort study of
      2598 children aged 3-6 years in Changsha, China. The lifetime prevalence of AR
      was assessed by a questionnaire administered by parents. Children's exposures to
      dioxide nitrogen (NO2), sulfur dioxide (SO2) and particulate matter with an
      aerodynamic diameter <= 10 MUm (PM10) during different pre- and post-natal timing
      windows were estimated using the measured concentrations at monitoring stations.
      The odds ratio (OR) and 95% confidence interval (CI) of childhood AR for exposure
      to different air pollutants during different timing windows were assessed by
      logistic regression model in terms of an interquartile range (IQR) increase in
      exposure level. RESULTS: Life-time prevalence of AR in preschool children (7.3%)
      was associated with both pre- and post-natal exposure to traffic-related air
      pollution (TRAP), but only significant during the third trimester of pregnancy
      with adjusted OR = 1.40 (95% CI: 1.08-1.82) for a 15 MUg/m3 increase in NO2 and
      during the first-year of life with adjusted OR = 1.36 (95% CI: 1.03-1.78) and
      1.54 (95% CI: 1.07-2.21) respectively for 11 and 12 MUg/m3 increase in NO2 and
      PM10. The association of early life exposure to TRAP with childhood AR was robust
      by adjusting for other air pollutants and timing windows. Sensitivity analysis
      indicated that the association was higher in the children who are male, young,
      with genetic predisposition by parental atopy, and living in damp houses.
      CONCLUSION: Early life exposure to traffic-related air pollutant during pregnancy
      and first-year of life may contribute to childhood AR.

PMID- 27888995
TI  - Efficacy of non-invasive ventilation as a rescue therapy for relieving dyspnea in
      patients with stable severe COPD.
AB  - Exertional Dyspnea is a troublesome symptom in chronic obstructive pulmonary
      disease (COPD) even after optimal therapy, which is a physiological and
      perceptional burden to limit their activities. Non-invasive ventilation (NIV)
      might provide rescue therapy for this population to relieve exertional dyspnea.
      This was a randomized crossover study in 18 patients with stable severe COPD.
      Exertional dyspnea was induced with maximal symptom-limited incremental cycle
      exercise. Then the patients would randomly receive oxygen or NIV plus oxygen
      therapy. Patients were crossed to another therapy in the second day. During the
      whole process, breathing pattern were monitored continuously until complete
      recovery. At every 30s interval, inspiratory capacity (IC) and Borg scale were
      assessed. Changes were compared between two interventions. Compared with oxygen
      therapy, NIV plus oxygen therapy resulted in increase of tidal volume and minute
      ventilation, decrease in dyspnea intensity at isotime (reduction of 1.0 +/- 2.0
      Borg units, p < 0.05) and a tendency but not statistically significant shortening
      in total dyspnea recovery time (326.2 +/- 132.0s vs 356.5 +/- 156.9s, p = 0.225).
      These improvements were negatively correlated with baseline FEV1 (r = -0.617, p <
      0.01). Subjects were divided into responders (n = 9) with dyspnea recovery time
      shortening > 30s or non-responders. Responder subgroup had significantly poorer
      pulmonary function in FEV1, FEV1%, IC than non-responder subgroup, indicating
      that NIV is effective as rescue therapy for exertional dyspnea in stable COPD
      with poorer pulmonary function. NIV as rescue therapy could help relieve dyspnea
      after exercise in patients with stable severe COPD with a poor pulmonary
      function.

PMID- 27888993
TI  - Identifying biomarkers for asthma diagnosis using targeted metabolomics
      approaches.
AB  - BACKGROUND: The diagnosis of asthma in children is challenging and relies on a
      combination of clinical factors and biomarkers including methacholine challenge,
      lung function, bronchodilator responsiveness, and presence of airway
      inflammation. No single test is diagnostic. We sought to identify a pattern of
      inflammatory biomarkers that was unique to asthma using a targeted metabolomics
      approach combined with data science methods. METHODS: We conducted a nested case
      control study of 100 children living in a peri-urban community in Lima, Peru. We
      defined cases as children with current asthma, and controls as children with no
      prior history of asthma and normal lung function. We further categorized
      enrollment following a factorial design to enroll equal numbers of children as
      either overweight or not. We obtained a fasting venous blood sample to
      characterize a comprehensive panel of targeted markers using a metabolomics
      approach based on high performance liquid chromatography-mass spectrometry.
      RESULTS: A statistical comparison of targeted metabolites between children with
      asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in
      relative concentrations of several metabolites: children with asthma had
      approximately 40-50% lower relative concentrations of ascorbic acid, 2
      isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when
      compared to children without asthma, and 70% lower relative concentrations of
      reduced glutathione (all p < 0.001 after Bonferroni correction). Moreover, a
      combination of 2-isopropylmalic acid and betaine strongly discriminated between
      children with asthma (2-isopropylmalic acid <= 13 077 normalized counts/second)
      and controls (2-isopropylmalic acid > 13 077 normalized counts/second and betaine
      <= 16 47 121 normalized counts/second). CONCLUSIONS: By using a metabolomics
      approach applied to serum, we were able to discriminate between children with and
      without asthma by revealing different metabolic patterns. These results suggest
      that serum metabolomics may represent a diagnostic tool for asthma and may be
      helpful for distinguishing asthma phenotypes.

PMID- 27888996
TI  - The effects of chronic obstructive pulmonary disease self-management
      interventions on improvement of quality of life in COPD patients: A meta
      analysis.
AB  - This article aimed to analyse the outcome of self-management randomised control
      trials and their impact upon chronic obstructive pulmonary disease patients'
      health outcomes using meta-analysis approach. PubMed, Scopus, CINAHL, Web of
      Science databases and Cochrane Library, were searched for articles between 1990
      and December 2015 by two researchers. Self-management programs significantly
      improved patients' quality of life across all domains of the St George
      Respiratory Questionnaire (SGRQ) (activity -2.21 (95% CI: -3.61 to -0.80), p =
      0.002; impact -3.30 (95% CI: -5.28 to -1.32), p = 0.001; symptoms -3.12 (95% CI: 
      4.94 to -1.03), p = 0.001; total -3.32 (95% CI: -4.60 to -2.04), p < 0.001), the
      six-minute walk test (-30.50 (95% CI: 3.32 to 57.68), p = 0.028), and across
      three domains of the chronic obstructive pulmonary disease self-efficacy scale
      (negative effect -1.22 (95% CI: -2.31 to -0.14), p = 0.027; physical exertion 
      1.27 (95% CI: -2.52 to -0.02), p = 0.047; behavioural risk factors -0.58 (95% CI:
      -0.99 to -0.16), p = 0.007). Subgroup analyses revealed that chronic obstructive
      pulmonary disease education (p < 0.01) was the strongest component with
      improvements on all aspects of the SGRQ and the six-minute walk test. Providing
      an exacerbation action plan significantly improved SGRQ activity and impact
      scores whilst exercise information had a positive effect on activity and symptom
      scores (p < 0.05). Interventions with a duration of less than five weeks (p <
      0.05) significantly improved symptom and activity scores, in addition to the
      number of patient hospital admissions. Thus, self-management interventions are
      effective at improving the health outcomes of chronic obstructive pulmonary
      disease patients, especially when disease education is provided.

PMID- 27888997
TI  - Comprehensive assessment of myositis-specific autoantibodies in
      polymyositis/dermatomyositis-associated interstitial lung disease.
AB  - OBJECTIVES: Myositis-specific autoantibodies (MSAs) are associated with clinical
      phenotypes in polymyositis/dermatomyositis (PM/DM). No study has investigated the
      clinical features based on comprehensive MSA assessment in PM/DM-associated
      interstitial lung disease (ILD). We aimed to determine the practical significance
      of MSAs in PM/DM-ILD. METHODS: Sixty consecutive PM/DM-ILD patients were
      retrospectively analysed. Serum MSAs were comprehensively measured using
      immunoprecipitation assay. Clinical features and prognosis were compared among
      MSA subgroups. RESULTS: Twenty-six (43.3%) PM/DM-ILD patients were anti-aminoacyl
      tRNA-synthetase antibody-positive (anti-ARS-positive), 15 (25.0%) were anti
      melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5
      positive), 3 (5%) were anti-signal recognition particle antibody-positive, 1
      (1.7%) was anti-transcriptional intermediary factor 1-gamma antibody-positive,
      and 15 (25%) were MSA-negative. There were significant differences in clinical
      features, including ILD form, serum ferritin and surfactant protein-D levels at
      ILD diagnosis, and high-resolution CT pattern among the anti-ARS-positive, anti
      MDA5-positive and MSA-negative groups. The anti-MDA5-positive group showed the
      lowest 90-day survival rate (66.7%, anti-MDA5-positive; 100%, anti-ARS-positive;
      100%, MSA-negative; P < 0.01). The anti-ARS-positive group had the highest 5-year
      survival rate (96%, anti-ARS-positive; 66.7%, anti-MDA5-positive; 68.3%, MSA
      negative, P = 0.02). Univariate analysis revealed that anti-ARS antibody was
      associated with better prognosis (HR = 0.45; 95% CI, 0.18-0.89; P = 0.02),
      whereas anti-MDA5 antibody was associated with poorer prognosis (HR = 1.90; 95%
      CI, 1.02-3.39; P = 0.04). CONCLUSIONS: The comprehensive MSA assessment
      demonstrated that anti-ARS and anti-MDA5 antibodies were two major MSAs, and the
      clinical features differed depending on MSA status in PM/DM-ILD. Assessment of
      anti-ARS and anti-MDA5 antibodies is practically useful for predicting clinical
      course and prognosis in PM/DM-ILD patients.

PMID- 27888998
TI  - Jay D. Iams, MD, AJOG Editor.

PMID- 27888999
TI  - Transabdominal ultrasound is appropriate.
AB  - Preterm birth remains a major cause of perinatal morbidity and mortality. A short
      cervix is strongly associated with spontaneous preterm birth. Professional
      organizations support cervical length screening for singleton gestations with a
      prior spontaneous preterm birth and second-trimester cervical length measurements
      between 16-24 weeks. All interventions used to decrease the risk of preterm birth
      in women with a short cervix are based on clinical trials that used transvaginal
      cervical length measurement, but transabdominal ultrasound has been shown to
      correlate well with transvaginal measurement in some observational studies.
      Transvaginal cervical length measurement is more accurate and more reliably
      obtained than the transabdominal approach. Conversely, transabdominal ultrasound
      could have the advantage of ease of implementation and, in general, is perceived
      by patients to be associated with less discomfort. Currently, there is no
      randomized clinical study that compares head-to-head the effectiveness of
      transvaginal vs transabdominal ultrasound for preterm birth risk screening. This
      point/counterpoint article summarizes the pros and cons of the 2 ultrasound
      approaches and debates whether transvaginal ultrasound should be used exclusively
      or if transabdominal ultrasound can be incorporated in cervical length screening
      for prevention of preterm birth.

PMID- 27889000
TI  - Not transabdominal!
AB  - Preterm birth remains a major cause of perinatal morbidity and mortality. A short
      cervix is strongly associated with spontaneous preterm birth. Professional
      organizations support cervical length screening for singleton gestations with a
      prior spontaneous preterm birth and second-trimester cervical length measurements
      between 16-24 weeks. All interventions used to decrease the risk of preterm birth
      in women with a short cervix are based on clinical trials that used transvaginal
      cervical length measurement, but transabdominal ultrasound has been shown to
      correlate well with transvaginal measurement in some observational studies.
      Transvaginal cervical length measurement is more accurate and more reliably
      obtained than the transabdominal approach. Conversely, transabdominal ultrasound
      could have the advantage of ease of implementation and, in general, is perceived
      by patients to be associated with less discomfort. Currently, there is no
      randomized clinical study that compares head-to-head the effectiveness of
      transvaginal vs transabdominal ultrasound for preterm birth risk screening. This
      point/counterpoint article summarizes the pros and cons of the 2 ultrasound
      approaches and debates whether transvaginal ultrasound should be used exclusively
      or if transabdominal ultrasound can be incorporated in cervical length screening
      for prevention of preterm birth.

PMID- 27889001
TI  - Treatment choice and psychiatry.

PMID- 27889002
TI  - The importance of rare diseases for psychiatry.

PMID- 27889003
TI  - What's in a name? Reclaiming mental illness.

PMID- 27889004
TI  - Ecstasy research: will increasing observational data aid our understanding of
      MDMA?

PMID- 27889005
TI  - Arbitrary classification of hospital policy regarding open and locked doors -
      Authors' reply.

PMID- 27889006
TI  - Arbitrary classification of hospital policy regarding open and locked doors.

PMID- 27889007
TI  - Nalmefene for alcohol dependence: a NICE decision?

PMID- 27889008
TI  - Unaiza Niaz-touching every corner of psychiatry.

PMID- 27889009
TI  - A wonderful lie.

PMID- 27889010
TI  - Neuropsychiatric aspects of concussion.
AB  - Over the past decade, concussion has become the most widely discussed injury in
      contact sports. However, concussions also occur in several other settings, such
      as non-contact sports, elderly individuals, young children, military personnel,
      and victims of domestic violence. Concussion is frequently undiagnosed as a cause
      of psychiatric morbidity, especially when the patient has no history of loss of
      consciousness or direct head trauma. Almost all of the extant literature focuses
      on traumatic brain injury and assumes that concussion is merely a mild form of
      traumatic brain injury, which has resulted in a lack of understanding about what
      concussion is, and how to diagnose, monitor, and treat its varied
      neuropsychiatric symptoms. In this Review, we address key issues so that the
      psychiatric clinician can better understand and treat patients with a clinical
      phenotype that might be the direct result of, or be exacerbated by, concussion.
      Future research needs to focus on prospective clinical trials in all affected
      patient populations (ie, those affected by concussion and those affected by
      various degrees of traumatic brain injury), the identification of reliable
      biomarkers that can be used to assist with diagnosis and treatment response, and
      the development of effective treatment interventions. Clearly differentiating
      concussion from traumatic brain injury is essential to achieve reliable and
      clinically relevant outcomes.

PMID- 27889012
TI  - Corrections.

PMID- 27889011
TI  - Limb amputation and other disability desires as a medical condition.
AB  - Some people have a profound dissatisfaction with what is considered an able
      bodied state by most others. These individuals desire to be disabled, by
      conventional standards. In this Review, we integrate research findings about the
      desire for a major limb amputation or paralysis (xenomelia). Neuropsychological
      and neuroimaging explorations of xenomelia show functional and structural
      abnormalities in predominantly right hemisphere cortical circuits of higher-order
      bodily representation, including affective and sexual aspects of corporeal
      awareness. These neural underpinnings of xenomelia do not necessarily imply a
      neurological cause, and a full understanding of the condition requires
      consideration of the interface between neural and social contributions to the
      bodily self and the concept of disability. Irrespective of cause, disability
      desires are accompanied by a disabling bodily dysphoria, in many respects similar
      to gender dysphoria, and we suggest that they should be considered a mental
      disorder.

PMID- 27889013
TI  - Methicillin-resistant Staphylococcus aureus infections: A review of the currently
      available treatment options.
AB  - This review is the result of discussions that took place at the 5th MRSA Working
      Group Consensus Meeting and explores the possible treatment options available for
      different types of infections due to methicillin-resistant Staphylococcus aureus
      (MRSA), focusing on those antibiotics that could represent a valid alternative to
      vancomycin. In fact, whilst vancomycin remains a viable option, its therapy is
      moving towards individualised dosing. Other drugs, such as the new
      lipoglycopeptides (oritavancin, dalbavancin and telavancin) and fifth-generation
      cephalosporins (ceftaroline and ceftobiprole), are showing good in vitro potency
      and in vivo efficacy, especially for patients infected with micro-organisms with
      higher vancomycin minimum inhibitory concentrations (MICs). Tedizolid is an
      attractive agent for use both in hospital and community settings, but the post
      marketing data will better clarify its potential. Daptomycin and linezolid have
      shown non-inferiority to vancomycin in the treatment of MRSA bacteraemia and non
      inferiority/superiority to vancomycin in the treatment of hospital-acquired
      pneumonia. Thus, several options are available, but more data from clinical
      practice, especially for invasive infections, are needed to assign specific roles
      to each antibiotic and to definitely include them in the new antibacterial
      armamentarium.

PMID- 27889014
TI  - [The role of alpha blockers in the treatment of lower urinary tract
      symptoms/benign prostatic hyperplasia: are all the same? Silodosin in "real
      life"].
AB  - The lower urinary tract symptoms (LUTS) are very common in men, particularly in
      people over 65 years. Benign prostatic hyperplasia (BPH) is the pathology most
      associated with LUTS in males, and is a common cause of impaired quality of life.
      Alpha blockers monotherapy represent the treatment of choice in patients with
      moderate-severe LUTS secondary to BPH. Silodosin is currently the most alpha1A
      uroselective alpha blocker, uroselectivity which has been confirmed in several
      studies both in vitro and in vivo. In this paper the main benefits of silodosin
      are analyzed in both phase III clinical trials (standard approach) as in "real
      life" (analyzing the study SiRE [Silodosin in Real-life Evaluation], phase IV
      study), to validate the test data recording and confirm the positive benefit-risk
      profile of silodosin in a context that can reflect more closely the clinical
      practice.

PMID- 27889015
TI  - Eye Health Needs to Be a Population Health Priority.

PMID- 27889016
TI  - Is it necessary to perform routine appendectomy for mucinous ovarian neoplasms? A
      retrospective study and meta-analysis.
AB  - OBJECTIVES: To evaluate whether routine appendectomy is necessary in all patients
      with mucinous borderline ovarian tumor (mBOT) or mucinous ovarian cancer (MOC)
      who undergo gynecologic surgery. METHODS: The database of Qilu Hospital was
      searched for women who underwent appendectomy in a primary surgery for an ovarian
      tumor between June 2005 and June 2015 and whose final diagnosis was mBOT, MOC or
      primary appendiceal tumor. A retrospective review was performed, as well as a
      meta-analysis of the literature to further validate the findings. RESULTS:
      Seventy-one patients, 29 with mBOT and 42 with malignant mucinous tumors
      (including 40 with primary MOC and 2 with appendiceal mucinous adenocarcinoma),
      underwent appendectomy at the time of primary surgery. Among those with mBOT, two
      (6.9%) appendices were grossly abnormal and pathologically diagnosed with
      appendiceal implantation by mBOT. In the 42 patients with malignant disease, five
      (12%) appendices had a grossly abnormal appearance, one (2.4%) was diagnosed with
      an appendiceal metastasis from MOC and two (4.7%) were primary appendiceal
      adenocarcinoma. For grossly normal appendices, only one (2.4%) was confirmed to
      have microscopic metastasis from MOC. The meta-analysis included a total of 914
      mBOT and MOC cases with appendectomies, including our current cases. The
      estimated rate of overall appendiceal pathology is 4.97%, and the pooled odds
      ratio (OR) showed statistical differences between MOC and mBOT (MOC vs. mBOT,
      OR=2.15, P<0.05). The estimated malignant pathology rate in macroscopically
      normal vs. abnormal appendices is 1.4% and 59%, respectively, with an estimated
      OR up to 97.5 (95% CI 28.1-338.5, P<0.05). CONCLUSION: There is not sufficient
      evidence to support a routine appendectomy for patients with a grossly normal
      appendix in mBOT and MOC. A careful intra-operative exploration of the appendix
      is crucial, but appendectomy is only warranted when the appendix is abnormal.

PMID- 27889018
TI  - Posterior Fossa Tumors.
AB  - Pediatric brain tumors are the leading cause of death from solid tumors in
      childhood. The most common posterior fossa tumors in children are
      medulloblastoma, atypical teratoid/rhabdoid tumor, cerebellar pilocytic
      astrocytoma, ependymoma, and brainstem glioma. Location, and imaging findings on
      computed tomography (CT) and conventional MR (cMR) imaging may provide important
      clues to the most likely diagnosis. Moreover, information obtained from advanced
      MR imaging techniques increase diagnostic confidence and help distinguish between
      different histologic tumor types. Here we discuss the most common posterior fossa
      tumors in children, including typical imaging findings on CT, cMR imaging, and
      advanced MR imaging studies.

PMID- 27889019
TI  - Extraparenchymal Lesions in Pediatric Patients.
AB  - Extraparenchymal lesions of childhood include neoplastic and nonneoplastic
      entities. Lesions affecting children are different from the most common entities
      affecting adults. Although there are imaging features that are highly suggestive
      of extraparenchymal origin, it can be difficult to distinguish extraparenchymal
      from intraparenchymal lesions. MR imaging is the examination of choice for the
      evaluation of extraparenchymal lesions given greater sensitivity and anatomic
      detail. Syndromic associations should be considered, especially for unusual
      lesions in the pediatric age group such as meningioma and schwannoma.

PMID- 27889017
TI  - Staging procedures in patients with mucinous borderline tumors of the ovary do
      not reveal peritoneal or omental disease.
AB  - OBJECTIVES: Staging in case of a borderline tumor of the ovary (BOT) is a
      controversial issue. Upstaging is not uncommon, but this occurs especially with
      presumed stage I serous borderline tumors. There are only a few documented cases
      of BOTs of non-serous histology that were not confined to the ovary. The aim of
      this study was to assess the incidence of non-invasive and invasive implants in
      the omentum and other (extra)pelvic peritoneal surfaces in patients with a
      mucinous BOT (mBOT). METHODS: A retrospective cohort study was performed in three
      hospitals in the Netherlands. All patients with a histopathological diagnosis of
      mBOT diagnosed from January 1st 1990 to December 1st 2015 were identified and
      included when the inclusion criteria were met. RESULTS: In total, 74 patients
      were included. Of these 74 patients, 46 (62.2%) underwent a staging procedure. In
      12 (26.1%) patients, only omental tissue was obtained, in 32 (69.6%) patients,
      omental tissue and peritoneal biopsies were obtained and in two (4.3%) patients,
      only peritoneal biopsies were obtained. No implants were seen upon microscopic
      examination in any of the patients. Two patients (3%) developed a recurrence.
      CONCLUSIONS: Because no extra-ovarian disease was found, staging procedures in
      the case of an mBOT may be omitted. However, the actual perioperative decision
      for staging or not should be taken in the context of a frozen section diagnosis,
      which is not always accurate and straightforward. Recurrence with malignant
      disease is rare after mBOT. The value of post-treatment surveillance seems
      limited after bilateral salpingo-oophorectomy.

PMID- 27889020
TI  - Tumor and Tumorlike Masses in Pediatric Patients that Involve Multiple Spaces.
AB  - There are several tumors and tumorlike masses involving multiple spaces in the
      pediatric brain. Accurate diagnosis of tumors and distinguishing them from
      tumorlike masses is an important aspect in the diagnostic workup and plays a key
      role for management and prognosis. Neuroimaging plays an important role in (1)
      identification of a brain mass, (2) determining its location, (3) demonstrating
      involvement of a single space versus multiple spaces, and (4) distinguishing a
      tumor from tumorlike masses.

PMID- 27889022
TI  - Advanced MR Imaging in Pediatric Brain Tumors, Clinical Applications.
AB  - Advanced MR imaging techniques, such as spectroscopy, perfusion, diffusion, and
      functional imaging, have improved the diagnosis of brain tumors in children and
      also play an important role in defining surgical as well as therapeutic responses
      in these patients. In addition to the anatomic or structural information gained
      with conventional MR imaging sequences, advanced MR imaging techniques also
      provide physiologic information about tumor morphology, metabolism, and
      hemodynamics. This article reviews the physiology, techniques, and clinical
      applications of diffusion-weighted and diffusion tensor imaging, MR spectroscopy,
      perfusion MR imaging, susceptibility-weighted imaging, and functional MR imaging
      in the setting of neuro-oncology.

PMID- 27889021
TI  - Neuroimaging of Peptide-based Vaccine Therapy in Pediatric Brain Tumors: Initial
      Experience.
AB  - The potential benefits of peptide-based immunotherapy for pediatric brain tumors
      are under investigation. Treatment-related heterogeneity has resulted in
      radiographic challenges, including pseudoprogression. Conventional MR imaging has
      limitations in assessment of different forms of treatment-related heterogeneity,
      particularly regarding distinguishing true tumor progression from efficacious
      treatment responses. Advanced neuroimaging techniques, including diffusion
      magnetic resonance (MR), perfusion MR, and MR spectroscopy, may add value in the
      assessment of treatment-related heterogeneity. Observations suggest that recent
      delineation of specific response criteria for immunotherapy of adult brain tumors
      is likely relevant to the pediatric population and further validation in
      multicenter pediatric brain tumor peptide-based vaccine studies is warranted.

PMID- 27889024
TI  - Brain Tumors in the Neonate.
AB  - Brain tumors can develop in the prenatal and neonatal time periods. Neuroimaging
      studies are crucial for the early detection of prenatal and neonatal brain
      tumors. Imaging allows for characterization of morphology, as well as the
      detection of hydrocephalus, local invasion, and distant spread. The imaging
      features of the more common neonatal brain tumors, including teratomas, choroid
      plexus tumors, ATRTs, and neoplasm mimics are described.

PMID- 27889023
TI  - Supratentorial Tumors in Pediatric Patients.
AB  - The breadth of tumors that can arise in the supratentorial brain in children is
      extensive. With the exception of those that result in seizures and the highly
      malignant histologies, supratentorial tumors may come to medical attention later
      compared with infratentorial tumors, as they are less commonly associated with
      ventricular obstruction. This article presents an overview of the neuroimaging
      characteristics of these entities, with particular attention to relevant features
      that may aid in narrowing the differential diagnosis, including correlation with
      demographics and clinical presentation.

PMID- 27889025
TI  - Pineal Region Masses in Pediatric Patients.
AB  - A review of pediatric pineal region tumors is provided with emphasis on advanced
      imaging techniques. The 3 major categories of pineal region tumors include germ
      cell tumors, pineal parenchymal tumors, and tumors arising from adjacent
      structures such as tectal astrocytomas. The clinical presentation, biochemical
      markers, and imaging of these types of tumors are reviewed.

PMID- 27889026
TI  - Imaging of the Sella and Parasellar Region in the Pediatric Population.
AB  - Masses in the sella and parasellar region comprise about 10% of all pediatric
      brain tumors but type and frequency differs from those in adults. Imaging is
      critical for diagnosis and characterization of these lesions. By assessing the
      site of origin, signal and contrast enhancement characteristics, and the presence
      or absence of characteristic patterns, differential diagnosis can narrow the
      possibilities. The clinical presentation is often characteristic for lesion type
      and should be considered. This article summarizes the characteristic imaging
      features of the most frequent pediatric tumors and tumor-mimicking lesions in
      children in this region.

PMID- 27889028
TI  - Pediatric Brain Tumors Update: Imaging Characterization of Pediatric Brain Tumors
      in the Central Nervous System Including Findings on Advanced MR Imaging
      Techniques.

PMID- 27889027
TI  - Pediatric Brain Tumors.

PMID- 27889029
TI  - Patient Perspective and Personal Journey of Treating a "Rare Cancer".
AB  - I was diagnosed with rare anal cancer. As overwhelming as the diagnosis was, it
      was complicated by limited treatment infrastructure and clinical research, side
      effect management, and lack of awareness and support organizations. Anal cancer
      encompasses so much more than receiving prescribed treatment and focusing on
      recovery. It requires patients to become experts on their disease, its treatment,
      and side effects. Even more challenging is finding support and advocacy. My
      experience has been difficult, complex, and arduous. It is hoped that this
      article will provide a voice for the many that have been silenced by stigma of
      anal cancer.

PMID- 27889030
TI  - Locally Recurrent Disease Related to Anal Canal Cancers.
AB  - Surgery for anal cancer is usually reserved for patients with persistent disease
      or local recurrence after definitive chemoradiation therapy. Patients with local
      recurrence should be re-evaluated for evidence of metastatic disease using
      positron emission tomography-computed tomography, and the local anatomy should be
      delineated with MRI. Eligible patients should undergo tailored surgery with the
      aim of achieving an R0 resection. Management is best undertaken within a
      specialized multidisciplinary setting. Careful patient selection and shared
      decision making are paramount for achieving acceptable patient-centered outcomes.

PMID- 27889032
TI  - Metastatic Anal Cancer and Novel Agents.
AB  - Squamous cell carcinoma of the anal canal (SCCA) represents an orphan disease.
      Although prior infection with human papilloma virus is associated with the
      development of SCCA, knowledge of this relationship has proven ineffective in
      identifying therapeutic agents that have activity in the management of metastatic
      SCCA. Combination chemotherapy with traditional cytotoxic agents has demonstrated
      efficacy in multiple small series. However, immune checkpoint blockade agents
      have demonstrated efficacy for patients with refractory metastatic SCCA; these
      agents hold promise in the horizon for patients with metastatic SCCA. Clinical
      trials should be considered for oncologists to manage patients with metastatic
      SCCA.

PMID- 27889031
TI  - Surveillance of Anal Canal Cancers.
AB  - Anal squamous cell cancer is most frequently a locoregional disease that is
      amenable to curative therapy in a majority of fit patients. Complete response
      rates after chemoradiotherapy (CRT) are good, with up to 75% of patients with no
      evidence of relapse on surveillance. Relapse is most frequently locoregional and
      is often amendable to salvage surgery with curative intent. Effective
      surveillance attempts to improve outcomes by identifying recurrent or persistent
      disease early, managing both acute and late toxicities, and offering reassurance
      to patients. This article explores the rationale and evidence for surveillance
      programs after definitive CRT.

PMID- 27889033
TI  - Uncommon Anal Neoplasms.
AB  - Uncommon neoplasms of the anal canal are associated with significant diagnostic
      dilemma in clinical practice and a high index of suspicion and pathologic
      expertise is needed. The incidence is likely to increase, particularly of small,
      incidental lesions found because of use of more frequent colonoscopy and high
      definition MRI. Generally treatment follows that of the same histologic subtype
      in other anatomic location. Surgical intervention is the cornerstone for cure in
      early/localized disease; however, removal of the anal canal is associated with
      significant morbidities and quality of life issues. A centralized global
      registry/database established under the auspices of the International Rare Care
      Initiative collaboration would be useful.

PMID- 27889035
TI  - Anal Dysplasia.
AB  - Anal dysplasia is a cytopathology term describing specific squamous cell
      morphology and represents a varying degree of benign changes. Often a source of
      confusion, the current iteration includes two types, low-grade and high-grade,
      and carries significant clinical implications. This article updates readers on
      the current definition of anal dysplasia, describes its incidence and prevalence,
      defines high-risk populations, and highlights diagnostics, treatment, and long
      term management strategies for patients with anal dysplasia.

PMID- 27889036
TI  - Diagnosis and Diagnostic Imaging of Anal Canal Cancer.
AB  - Anal canal cancer is an uncommon malignancy but one that is often curable with
      optimal therapy. Owing to its unique location, histology, risk factors, and usual
      presentation, a careful diagnostic approach is warranted. This approach includes
      an excellent history and physical examination, including digital rectal
      examination, laboratory data, and comprehensive imaging. Anal cancer staging and
      formulation of a treatment plan depends on accurate imaging data. Modern
      radiographic techniques have improved staging quality and accuracy, and a
      thorough knowledge of anal anatomy is paramount to the optimal multidisciplinary
      treatment of this disease.

PMID- 27889037
TI  - Pathology of Anal Cancer.
AB  - Anal canal cancer is rather an uncommon disease but its incidence is increasing.
      Squamous cell carcinoma (SCC) is the most frequent primary anal neoplasm and can
      encompass a variety of morphologies. HPV infection has a key role in precancerous
      lesions and cancer development by the production of E6 and E7 oncoproteins. Anal
      squamous precancerous lesions are now classified according to the same criteria
      and terminology as their cervical counterparts. The p16 expression by
      immunohistochemistry is a surrogate marker for human papilloma virus (HPV). Many
      other tumor types can arise in the anal canal, including adenocarcinomas,
      neuroendocrine tumors, malignant melanomas, lymphomas and various types of
      mesenchymal tumors. For differential diagnosis, immunostaining markers such as
      CK5/6 and p63 can be used to distinguish SCC and CK7 for adenocarcinoma. Other
      classical panels can also be applied as in other locations. Currently, there are
      no biomarkers able to predict prognosis or response to treatment in clinical
      practice.

PMID- 27889034
TI  - Human Immunodeficiency Virus/AIDS, Human Papillomavirus, and Anal Cancer.
AB  - Anal cancer is an increasingly common non-AIDS-defining cancer among individuals
      infected with the human immunodeficiency virus (HIV). It is associated with human
      papillomavirus (HPV). HPV16 is the most common genotype detected in anal cancers.
      The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV
      vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV
      infected individuals. Standard treatment has been fluorouracil and mitomycin (or
      cisplatin) plus radiation. Continued studies are needed to test new treatment
      strategies in HIV-infected patients with anal cancer to determine which treatment
      protocols provide the best therapeutic index.

PMID- 27889038
TI  - Treatment of the Primary Tumor in Anal Canal Cancers.
AB  - Radical concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C (MMC)
      remains the standard of care for squamous cell carcinoma of the anus. Phase III
      trials over 2 decades have used combined radiation doses of 50 to 60 Gy with
      concurrent fluoropyrimidines, MMC, or cisplatin in various doses and schedules.
      Modern radiotherapy techniques allow the production of highly conformal plans,
      decreasing radiation doses to the organs at risk and ensuring a shorter overall
      treatment time without the need for treatment breaks. These techniques offer the
      potential to improve compliance and even escalate doses of radiation.

PMID- 27889039
TI  - Epidemiology of Anal Canal Cancer.
AB  - Anal cancer is a rare malignancy, although its incidence has been increasingly in
      recent decades. This article discusses risk factors for anal cancer and how these
      risk factors affect the changing demographics of this disease.

PMID- 27889041
TI  - Anal Cancer 2016.

PMID- 27889040
TI  - Evolution and Management of Treatment-Related Toxicity in Anal Cancer.
AB  - Over the past several decades, clinical trials have demonstrated improved disease
      related outcomes in the definitive treatment of anal cancer. Although treatment
      with radiation and concurrent chemotherapy results in high rates of cure,
      significant acute and late toxicities are seen. This review focuses on the
      evolution of treatment-related toxicity for anal cancer. Management of these
      adverse effects is reviewed, as are future directions in anal cancer treatment
      and their impact on toxicity.

PMID- 27889042
TI  - Preface.

PMID- 27889044
TI  - Leadless Pacemakers.
AB  - Leadless pacing is an emerging technology with the potential to significantly
      improve outcomes associated with the need for long-term pacing. Specifically, the
      major advantage of leadless systems is abolishing the need for transvenous leads
      and subcutaneous pockets, both of which account for most adverse events
      associated with traditional pacemakers. Two leadless pacemakers are currently
      available: the Nanostim (leadless cardiac pacemaker [LCP]) device (St. Jude
      Medical, Sylmar, California) and the Micra Transcatheter pacing system
      (Medtronic, Minneapolis, Minnesota). These 2 pacemakers have shown promising
      results in clinical trials. In conclusion, in this review we summarize the
      results of the 2 investigational device exemption trials and compare the pros and
      cons of these devices to traditional transvenous pacemakers.

PMID- 27889043
TI  - PR-Interval Components and Atrial Fibrillation Risk (from the Atherosclerosis
      Risk in Communities Study).
AB  - Reports on the association between the PR-interval and atrial fibrillation (AF)
      are conflicting. We hypothesized that inconsistencies stem from that fact that
      the PR-interval represents a composite of several distinct components. We
      examined the associations of the PR-interval and its components (P-wave onset to
      P-wave peak duration, P-wave peak to P-wave end duration, and PR-segment) with
      incident AF in 14,924 participants (mean age 54 +/- 5.8 years; 26% black; 55%
      women) from the Atherosclerosis Risk In Communities study. The PR-interval and
      its components were automatically measured at baseline (1987 to 1989) from
      standard 12-lead electrocardiograms. PR-interval >200 ms was considered prolonged
      and values above the ninety-fifth percentile defined abnormal PR-interval
      components. AF was ascertained during follow-up through December 31, 2010. Over a
      median follow-up of 21.2 years, 1,985 participants (13%) developed AF. Prolonged
      PR-interval was associated with an increased risk of AF (hazard ratio [HR] 1.19,
      95% confidence interval [CI] 1.02 to 1.40). However, PR-interval components
      showed varying levels of association with AF (P-wave onset to P-wave peak
      duration: HR 1.57, 95% CI 1.31 to 1.88; P-wave peak to P-wave end duration: HR
      1.20, 95% CI 0.99 to 1.46; and PR-segment: HR 1.05, 95% CI 0.85 to 1.29). In
      addition, the components of the PR-interval had weak-to-moderate correlation with
      each other (correlation r ranged from -0.44 to 0.06). In conclusion, our findings
      suggest the PR-interval represents a composite of distinct components that are
      not uniformly associated with AF. Without considering the contribution of each
      component, inconsistent associations between the PR-interval and AF are
      inevitable.

PMID- 27889045
TI  - Technology to Help Promote Physical Activity.

PMID- 27889046
TI  - Ballooning Pattern and Related Outcome in Takotsubo Syndrome.

PMID- 27889047
TI  - Sex differences in the association between stroke and bone mineral density in
      elderly Koreans: The Korean National Health and Nutrition Examination Survey,
      2008-2010.
AB  - OBJECTIVES: The aim of this study was to investigate whether osteoporosis is more
      prevalent in elderly Korean people who have had a stroke and whether the
      association differs by sex. STUDY DESIGN: A total of 3806 elderly subjects (1951
      men and 1855 women) from the Korea National Health and Nutrition Examination
      Survey were included in this study. Stroke history was determined by self
      administered questionnaire. Bone mineral density (BMD) was measured at the lumbar
      spine, total hip, and neck of the femur using dual-energy X-ray absorptiometry.
      It was categorized as normal, osteopenia, or osteoporosis. RESULTS: In men who
      had had a stroke, the prevalence of osteoporosis was greater than that of both
      osteopenia and normal BMD, and the prevalence of osteopenia was greater than that
      of normal BMD (p<0.001). However, there were no significant differences in BMD
      level among women who had had a stroke. Men who had had a stroke undertook less
      vigorous exercise and moderate-or-vigorous exercise than did men who had not had
      a stroke (p=0.002 and 0.030, respectively). After adjusting for all covariates,
      the mean BMD at the lumbar spine, total hip and neck of the femur was lower in
      men who had had a stroke than in men who had not (p=0.034, 0.002, and 0.005,
      respectively). There were no significant differences in mean BMD at any of the
      three sites between women who had and women who had not had a stroke. CONCLUSION:
      Men who have had a stroke have a higher prevalence of osteopenia and
      osteoporosis, and have lower BMD at the total hip and femur neck than men who
      have not had a stroke.

PMID- 27889048
TI  - The use of high-dose estrogens for the treatment of breast cancer.
AB  - Estrogens are known to stimulate the growth of breast cancer but they are also an
      effective treatment for this disease (this has been termed the 'estrogen
      paradox'). The fact that estrogens can be an effective treatment for breast
      cancer is something that has almost been forgotten, whereas the fear for
      estrogens remains. This paper reviews the use of estrogens for the treatment of
      breast cancer and identifies possible applications. The data summarised in this
      review demonstrate that high-dose estrogens are effective for the treatment of
      advanced breast cancer, both as first-line treatment as well as for treatment
      after occurrence of endocrine resistance to TAM and AIs. Essential for efficacy
      is an extended period of estrogen deprivation before the tumour is subject to
      estrogen treatment (the gap hypothesis). Research on the mechanism of action has
      shown that apoptosis induced by estrogens is regulated via the estrogen receptor
      and growth factor signalling pathways. High-dose estrogens have a negative safety
      image, especially in terms of side-effects and increased rates of cardiovascular
      disease, but the safety data reviewed in this paper do not give rise to major
      concerns. Taking into account their side-effect profile together with their
      observed clinical efficacy, high-dose estrogens should be considered a valuable
      alternative to chemotherapy in selected patients.

PMID- 27889049
TI  - Web-based interventions for menopause: A systematic integrated literature review.
AB  - Advances in computer and Internet technologies have allowed health care providers
      to develop, use, and test various types of Web-based interventions for their
      practice and research. Indeed, an increasing number of Web-based interventions
      have recently been developed and tested in health care fields. Despite the great
      potential for Web-based interventions to improve practice and research, little is
      known about the current status of Web-based interventions, especially those
      related to menopause. To identify the current status of Web-based interventions
      used in the field of menopause, a literature review was conducted using multiple
      databases, with the keywords "online," "Internet," "Web," "intervention," and
      "menopause." Using these keywords, a total of 18 eligible articles were analyzed
      to identify the current status of Web-based interventions for menopause. Six
      themes reflecting the current status of Web-based interventions for menopause
      were identified: (a) there existed few Web-based intervention studies on
      menopause; (b) Web-based decision support systems were mainly used; (c) there was
      a lack of detail on the interventions; (d) there was a lack of guidance on the
      use of Web-based interventions; (e) counselling was frequently combined with Web
      based interventions; and (f) the pros and cons were similar to those of Web-based
      methods in general. Based on these findings, directions for future Web-based
      interventions for menopause are provided.

PMID- 27889050
TI  - Frailty and multimorbidity: Two related yet different concepts.
AB  - The extension of life expectancy is a global phenomenon. The growth in the ageing
      population has created a new health scenario in which there is a higher
      prevalence of frailty and multimorbidity. The attention received by both
      conditions derives from their strong association with disability,
      hospitalization, and death. The aim of the present paper is to conceptualize and
      differentiate these terms and to discuss their interrelations. We conclude that,
      yet related, they represent two different clinical conditions. Frailty identifies
      the increased vulnerability to stressors due to a dynamic, non-linear, and
      multidimensional depletion of physiological reserve and redundancy, whereas
      multimorbidity refers to the coexistence of two or more clinically manifest
      chronic diseases.

PMID- 27889051
TI  - The trajectory of negative mood and depressive symptoms over two decades.
AB  - OBJECTIVE: Research aimed at understanding the temporal characteristics of
      depressive symptoms and negative mood in an older female population is lacking,
      despite the relationship between the two factors being well established. The aim
      of this study was to examine the characteristics of negative mood scores and
      depressive symptom scores in a longitudinal sample of women transitioning from
      mid-life to late life. STUDY DESIGN: This study was a longitudinal assessment of
      variables drawn from an epidemiological prospective study of women's healthy
      ageing. Scores were analysed using General Linear Mixed Models. MAIN OUTCOME
      MEASURES: Negative mood scores derived from the Affectometer 2 were assessed at
      11 time points spanning 20 years. Depressive symptom scores were assessed using
      the Centre for Epidemiological Studies Depression Scale (CESD), administered in
      2002, 2004 and 2012. RESULTS: Mean negative mood scores reduced significantly
      between 1992 and 2012, as did mean CESD scores between 2002 and 2012. Mean
      negative mood scores reduced by 0.007 for each year of increasing age. For
      depressive symptoms, a reduction in mean score of 0.15 was found for each year of
      increase in age. CONCLUSION: Depressive symptom scores and negative mood scores
      decreased significantly over time.

PMID- 27889052
TI  - Types of oral contraceptives and breast cancer survival among women enrolled in
      Medicaid: A competing-risk model.
AB  - INTRODUCTION: Oral contraceptive pills have been implicated in the
      pathophysiology of breast cancer. Although many studies have examined the
      relationship between combined oral contraceptives (COCs) and breast cancer, there
      is a paucity of literature that discusses progestin-only oral contraceptives
      (POCs) and breast cancer. The purpose of this investigation is to examine
      potential associations between different types of oral contraceptives and breast
      cancer mortality in the South Carolina Medicaid population among different
      racial/ethnic groups. METHODS: Subjects included 4816 women diagnosed with breast
      cancer between 2000 and 2013. Kaplan-Meier curves were calculated to determine
      time-to-mortality rates among users of oral contraceptives. Competing-risks
      models and Cox multivariate survival models were used to estimate the hazard
      ratios (HRs) and 95% confidence intervals (CIs) of breast cancer and other-cause
      mortality, as well as all-cause mortality. RESULTS: POCs were associated with a
      significantly decreased risk of breast cancer mortality (HR: 0.07; 95% CI: 0.01,
      0.52) and a non-significant increased risk of all-cause mortality (HR: 1.04; 95%
      CI: 0.52, 2.07). COCs increased the risk of breast cancer mortality (HR: 1.61;
      95% CI: 1.14, 2.28) and all-cause mortality (HR: 1.83; 95% CI: 1.30, 2.57).
      CONCLUSION: Use of POCs may be associated with a decreased risk of breast cancer
      mortality. Due to the small sample size of POC users in the current study,
      additional research is needed to confirm these findings.

PMID- 27889053
TI  - Osteoporosis in postmenopausal women living with HIV.
AB  - The widespread availability of effective antiretroviral therapy (ART) has
      transformed HIV from a life-limiting condition to one with near-normal life
      expectancy. HIV is associated with an increased risk of osteopenia and
      osteoporosis, with people living with HIV (PLHIV) potentially experiencing these
      conditions at a younger age than their HIV-negative counterparts. The mechanisms
      driving bone disease in HIV are complex and include: an increased prevalence of
      traditional risk factors; other comorbid conditions; and HIV-associated factors
      such as viral effects, systemic inflammation, and ART-related factors. One-third
      of PLHIV in the United Kingdom are female, and increasing numbers of women living
      with HIV (WLHIV) are reaching menopausal age. Oestrogen decline in the context of
      an elevated background risk of poor bone health results in WLHIV being at greater
      risk of osteoporosis than women without HIV. European HIV guidelines therefore
      recommend routine screening of postmenopausal WLHIV using FRAX(c) for clinical
      risk factors, with or without bone mineral density scanning. Data support the use
      of calcium and vitamin D supplementation, and bisphosphonates in the treatment of
      osteoporosis in PLHIV. Additionally, some patients with confirmed osteoporosis
      may benefit from a switch to an ART agent with a better bone safety profile.
      However, there remains a notable paucity of data on HIV and menopause, including
      the impact of hormone replacement therapy on the bone health of WLHIV. In
      conclusion, it is important that clinicians are aware that postmenopausal WLHIV
      are a group at particular risk of bone disease, who require proactive screening
      and advice about preventative measures.

PMID- 27889054
TI  - Tocotrienols, health and ageing: A systematic review.
AB  - OBJECTIVES: A systematic review of studies was undertaken to evaluate the
      potential effect of intake of tocotrienols or circulating levels of tocotrienols
      on parameters associated with successful ageing, specifically in relation to
      cognitive function, osteoporosis and DNA damage. METHODS: Following PRISMA
      guidelines a systematic review of epidemiological observational studies and
      clinical trials was undertaken. Inclusion criteria included all English language
      publications in the databases PubMed and Scopus, through to the end of July 2016.
      RESULTS: Evidence from prospective and case-control studies suggested that
      increased blood levels of tocotrienols were associated with favorable cognitive
      function outcomes. A clinical trial of tocotrienol supplementation for 6 months
      suggested a beneficial effect of intake on DNA damage rates, but only in elderly
      people. Regarding osteoporosis, only in vitro studies with cultures of human bone
      cells were identified, and these demonstrated significant inhibition of
      osteoclast activity and promotion of osteoblast activity. CONCLUSIONS: Research
      in middle-aged and elderly humans suggests that tocotrienols have a potential
      beneficial anti-ageing action with respect to cognitive impairment and DNA
      damage. Clinical trials are required to elucidate these effects.

PMID- 27889055
TI  - Medical or surgical management of fibroids? An internet survey of gynecologists'
      views.
AB  - AIM: To assess the attitudes of gynecologists toward symptomatic fibroids and
      analyze which factors influence their choice of treatment. MATERIAL AND METHOD:
      We surveyed the attitude of Belgian gynecologists toward patients' cases. We used
      a vignette of a woman with symptomatic fibroids and modified 3 factors: her age,
      her parity and her desire for pregnancy, thereby establishing 12 different cases.
      We ensured that each gynecologist (n=1437) received one case, chosen randomly, by
      email. The gynecologists were asked whether and how they would treat the patient.
      RESULTS: Replies were received from 337 gynecologists (a 23% response rate). Of
      the 337, 116 (34%) would prescribe a medical treatment only; in this group, 29%
      specified acetate ulipristal a selective progesterone receptor modulator (SPRM)
      and 27% indicated progestins. Of the sample of 337 responders, another 116 (34%)
      would begin with medical treatment (70% an SPRM) and then proceed to surgery. Of
      the 337 gynecologists, 75 (22%) would perform surgery only. The preferred
      surgical treatments were myomectomy (53/75; 71%) and hysterectomy (19/75; 25%)
      when surgery was suggested as a first step, and myomectomy (91/115; 79%) and
      hysterectomy (18/115; 16%) when it was preceded by medical treatment. The choice
      of treatment varied significantly in relation to the 12 vignettes (p<0.01). When
      we grouped the vignettes there was no significant variation in relation to age or
      parity, but a there was significant variation (p<0.001) in relation to desire to
      achieve pregnancy. CONCLUSION: We observed that, in women with symptomatic
      fibroids, the desire retain fertility is respected. Moreover, SPRM is
      increasingly used for symptomatic patients.

PMID- 27889056
TI  - In memory of Professor Galen S. Wagner M.D., Ph.D. (1939-2016): our mentor,
      colleague and friend.

PMID- 27889057
TI  - Algorithm for the automatic computation of the modified Anderson-Wilkins
      acuteness score of ischemia from the pre-hospital ECG in ST-segment elevation
      myocardial infarction.
AB  - BACKGROUND: The acuteness score (based on the modified Anderson-Wilkins score)
      estimates the acuteness of ischemia based on ST-segment, Q-wave and T-wave
      measurements obtained from the electrocardiogram (ECG) in patients with ST
      Elevation Myocardial Infarction (STEMI). The score (range 1 (least acute) to 4
      (most acute)) identifies patients with substantial myocardial salvage potential
      regardless of patient reported symptom duration. However, due to the complexity
      of the score, it is not used in clinical practice. Therefore, we aimed to develop
      a reliable algorithm that automatically computes the acuteness score. METHODS: We
      scored 50 pre-hospital ECGs from STEMI patients, manually and by the automated
      algorithm. We assessed the reliability test between the manual and automated
      algorithm by interclass correlation coefficient (ICC) and Bland-Altman plot.
      RESULTS: The ICC was 0.84 (95% CI 0.72-0.91), P<0.0001. The mean difference
      between manual and automated acuteness score was 0.17+/-0.66. In only two cases,
      there was a major disagreement between the two scores. There was an excellent
      agreement between the scores for the remaining 48 ECGs, all within the upper
      (1.46) and lower (-1.12) limits of agreement. CONCLUSION: In conclusion, we have
      developed an automated algorithm for measurement of the modified Anderson-Wilkins
      ECG acuteness score from the pre-hospital ECG in STEMI patients. This automated
      algorithm is highly reliable, can be applied in daily practice for research
      purposes and may be implemented in commercial automated ECG analysis programs to
      achieve practical use for decision support in the acute phase of STEMI.

PMID- 27889059
TI  - Chad Genetic Diversity Reveals an African History Marked by Multiple Holocene
      Eurasian Migrations.
AB  - Understanding human genetic diversity in Africa is important for interpreting the
      evolution of all humans, yet vast regions in Africa, such as Chad, remain
      genetically poorly investigated. Here, we use genotype data from 480 samples from
      Chad, the Near East, and southern Europe, as well as whole-genome sequencing from
      19 of them, to show that many populations today derive their genomes from ancient
      African-Eurasian admixtures. We found evidence of early Eurasian backflow to
      Africa in people speaking the unclassified isolate Laal language in southern Chad
      and estimate from linkage-disequilibrium decay that this occurred 4,750-7,200
      years ago. It brought to Africa a Y chromosome lineage (R1b-V88) whose closest
      relatives are widespread in present-day Eurasia; we estimate from sequence data
      that the Chad R1b-V88 Y chromosomes coalesced 5,700-7,300 years ago. This
      migration could thus have originated among Near Eastern farmers during the
      African Humid Period. We also found that the previously documented Eurasian
      backflow into Africa, which occurred ~3,000 years ago and was thought to be
      mostly limited to East Africa, had a more westward impact affecting populations
      in northern Chad, such as the Toubou, who have 20%-30% Eurasian ancestry today.
      We observed a decline in heterozygosity in admixed Africans and found that the
      Eurasian admixture can bias inferences on their coalescent history and confound
      genetic signals from adaptation and archaic introgression.

PMID- 27889058
TI  - Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa.
AB  - Retinitis pigmentosa (RP) is the most frequent form of inherited retinal
      dystrophy. RP is genetically heterogeneous and the genes identified to date
      encode proteins involved in a wide range of functional pathways, including
      photoreceptor development, phototransduction, the retinoid cycle, cilia, and
      outer segment development. Here we report the identification of biallelic
      mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals
      with autosomal-recessive RP from five unrelated families. REEP6 is a member of
      the REEP/Yop1 family of proteins that influence the structure of the endoplasmic
      reticulum but is relatively unstudied. The six variants identified include three
      frameshift variants, two missense variants, and a genomic rearrangement that
      disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6
      expression and confirmed the expression of a retina-specific isoform REEP6.1,
      which is specifically affected by one of the frameshift mutations. Expression of
      the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and
      the REEP6.1 frameshift mutant in cultured cells suggest that these changes
      destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used
      to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant
      identified in one RP-affected individual. The homozygous knock-in mice mimic the
      clinical phenotypes of RP, including progressive photoreceptor degeneration and
      dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in
      retinal homeostasis and highlights a pathway previously uncharacterized in
      retinal dystrophy.

PMID- 27889060
TI  - Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2
      Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic Atrophy.
AB  - Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of
      severe disorders characterized by seizures, interictal epileptiform activity with
      a disorganized electroencephalography background, developmental regression or
      retardation, and onset before 1 year of age. Among a cohort of 57 individuals
      with epileptic encephalopathy, we ascertained two unrelated affected individuals
      with EOEE associated with developmental impairment and autosomal-recessive
      variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of
      AP3B2 in 86 unrelated individuals with EOEE led to the identification of an
      additional family. We gathered five additional families with eight affected
      individuals through the Matchmaker Exchange initiative by matching autosomal
      recessive mutations in AP3B2. Reverse phenotyping of 12 affected individuals from
      eight families revealed a homogeneous EOEE phenotype characterized by severe
      developmental delay, poor visual contact with optic atrophy, and postnatal
      microcephaly. No spasticity, albinism, or hematological symptoms were reported.
      AP3B2 encodes the neuron-specific subunit of the AP-3 complex. Autosomal
      recessive variations of AP3B1, the ubiquitous isoform, cause Hermansky-Pudlak
      syndrome type 2. The only isoform for the delta subunit of the AP-3 complex is
      encoded by AP3D1. Autosomal-recessive mutations in AP3D1 cause a severe disorder
      cumulating the symptoms of the AP3B1 and AP3B2 defects.

PMID- 27889061
TI  - Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia,
      Macrocephaly, Albinism, and Deafness.
AB  - Human MITF is, by convention, called the "microphthalmia-associated transcription
      factor" because of previously published seminal mouse genetic studies; however,
      mutations in MITF have never been associated with microphthalmia in humans. Here,
      we describe a syndrome that we term COMMAD, characterized by coloboma,
      osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. COMMAD is
      associated with biallelic MITF mutant alleles and hence suggests a role for MITF
      in regulating processes such as optic-fissure closure and bone development or
      homeostasis, which go beyond what is usually seen in individuals carrying
      monoallelic MITF mutations.

PMID- 27889063
TI  - Andree Gruslin award lecture: Metabolomics as an important modality to better
      understand preeclampsia.
AB  - Preeclampsia (PE) is a complex disorder that affects 3-5% of all pregnancies and
      is a leading cause of maternal and fetal morbidity and mortality. To date, the
      heterogeneity of clinical presentation, disease severity and outcomes have
      limited significant advances in early prediction, diagnosis, and therapeutic
      intervention of PE. The rapidly expanding field of metabolomics, which has the
      capacity to quantitatively detect low molecular weight compounds (metabolites) in
      tissue and biological fluids, shows tremendous promise in gaining a better
      understanding of PE. This review will discuss this emerging field and its
      contribution to recent advances in the understanding of PE pathophysiology, and
      identification of early predictive metabolic biomarkers for this complex
      disorder.

PMID- 27889064
TI  - Summary of the British Association of Pediatric Surgeons (63rd) congress in
      Amsterdam, the Netherlands, July 20th-22nd, 2016.
AB  - This is a review of the 63rd British Association of Pediatric Surgeons (BAPS)
      annual conference which was held in July 2016 in Amsterdam in the Netherlands.
      This congress issue contains papers presented during the open sessions and
      transcripts based on invited lectures.

PMID- 27889062
TI  - Monoallelic Mutations in the Translation Initiation Codon of KLHL24 Cause Skin
      Fragility.
AB  - The genetic basis of epidermolysis bullosa, a group of genetic disorders
      characterized by the mechanically induced formation of skin blisters, is largely
      known, but a number of cases still remain genetically unsolved. Here, we used
      whole-exome and targeted sequencing to identify monoallelic mutations, c.1A>G and
      c.2T>C, in the translation initiation codon of the gene encoding kelch-like
      protein 24 (KLHL24) in 14 individuals with a distinct skin-fragility phenotype
      and skin cleavage within basal keratinocytes. Remarkably, mutation c.1A>G
      occurred de novo and was recurrent in families originating from different
      countries. The striking similarities of the clinical features of the affected
      individuals point to a unique and very specific pathomechanism. We showed that
      mutations in the translation initiation codon of KLHL24 lead to the usage of a
      downstream translation initiation site with the same reading frame and formation
      of a truncated polypeptide. The pathobiology was examined in keratinocytes and
      fibroblasts of the affected individuals and via expression of mutant KLHL24, and
      we found mutant KLHL24 to be associated with abnormalities of intermediate
      filaments in keratinocytes and fibroblasts. In particular, KLHL24 mutations were
      associated with irregular and fragmented keratin 14. Recombinant overexpression
      of normal KLHL24 promoted keratin 14 degradation, whereas mutant KLHL24 showed
      less activity than the normal molecule. These findings identify KLHL24 mutations
      as a cause of skin fragility and identify a role for KLHL24 in maintaining the
      balance between intermediate filament stability and degradation required for skin
      integrity.

PMID- 27889065
TI  - Letter to the Editor: "Post-traumatic liver and splenic pseudoaneurysms in
      children: Diagnosis, management, and follow-up screening using contrast enhanced
      ultrasound (CEUS)" by Durkin et al J Pediatr Surg 51 (2016) 289-292.

PMID- 27889066
TI  - Does thoracoscopy have advantages over open surgery for asymptomatic congenital
      lung malformations? An analysis of 1626 resections.
AB  - AIM: The apparent incidence of antenatally diagnosed congenital lung
      malformations (CLM) is rising (1 in 3000), and the majority undergo elective
      resection even if asymptomatic. Thoracoscopy has been popularized, but early
      series report high conversion rates and significant complications. We aimed to
      perform systematic review/meta-analysis of outcomes of thoracoscopic vs open
      excision of asymptomatic CLMs. METHODS: A systematic review according to PRISMA
      guidelines was performed. Data were extracted for all relevant studies (2004
      2015) and Rangel quality scores calculated. Analysis was on 'intention to treat'
      basis for thoracoscopy and asymptomatic lung lesions. Meta-analysis was performed
      using the addon package METAN of the statistical package STATA14TM; p<0.05 was
      considered significant. RESULTS: 36 studies were eligible, describing 1626 CLM
      resections (904 thoracoscopic, 722 open). There were no randomized controlled
      trials. Median quality score was 14/45 (IQR 6.5) 'poor'. 92/904 (10%)
      thoracoscopic procedures were converted to open. No deaths were reported. Meta
      analysis showed that regarding thoracoscopic procedures, the total number of
      complications was significantly less (OR 0.63, 95% CI 0.43, 0.92; p<0.02, 12
      eligible series, 912 patients, 404 thoracoscopic). Length of stay was 1.4days
      shorter (95%CI 2.40, 0.37;p<0.01). Length of operation was 37 min longer (95% CI
      18.96, 54.99; p<0.01). Age, weight, and number of chest tube days were similar.
      There was heterogeneity (I2 30%, p=0.15) and no publication bias seen.
      CONCLUSIONS: A reduced total complication rate favors thoracoscopic excision over
      thoracotomy for asymptomatic antenatally diagnosed CLMs. Although operative time
      was longer, and open conversion may be anticipated in 1/10, the overall length of
      hospital stay was reduced by more than 1day. LEVEL OF EVIDENCE: 4 (based on
      lowest level of article analyzed in meta-analysis/systematic review).

PMID- 27889068
TI  - Diosgenin-caused changes of the adrenal gland histological parameters in a rat
      model of the menopause.
AB  - Diosgenin, a steroidal sapogenin of natural origin, has demonstrated benefits
      when it comes to the treatment of malignancies, cardiovascular issues and
      menopausal symptoms. In this study, we investigated the histological changes of
      the adrenal gland after diosgenin application in a rat model of the menopause.
      Middle-aged, acyclic female Wistar rats were divided into control (C; n=6) and
      diosgenin treated (D; n=6) groups. Diosgenin (100mg/kg b.w./day) was orally
      administered for four weeks, while C group received the vehicle alone. A
      histological approach included design-based stereology, histochemistry and
      immunohistochemistry. The adrenal cortex volume decreased in D females by 15%
      (p<0.05) while the volume of adrenal medulla increased (p<0.05) by 64%, compared
      to the same parameters in C group. Volume density of the zona glomerulosa
      (expressed per absolute adrenal gland volume) in D rats increased (p<0.05) by 22%
      in comparison with C animals. Diosgenin treatment decreased (p<0.05) the volume
      density of the zona fasciculata (expressed per volume of adrenal cortex) by 15%
      when compared to C females. Absolute volume of the zona reticularis in D group
      decreased (p<0.05) by 38% in comparison with the same parameter in C rats. Also,
      after diosgenin application, the volume density of the zona reticularis
      (expressed per volume of adrenal cortex) and the zona reticularis cell volume
      were decreased by 51% and 20% (p<0.05) respectively, compared to C animals. Our
      results, reflecting a decrease in many stereological parameters of the adrenal
      cortex, indicate that diosgenin took over the role of corticosteroid precursors
      and became incorporated into steroidogenesis.

PMID- 27889067
TI  - An Atypical Withdrawal Syndrome in Neonates Prenatally Exposed to Gabapentin and
      Opioids.
AB  - We report a retrospective case series of 19 infants exposed to both opioids and
      gabapentin prenatally. We describe a unique behavioral phenotype in 15 of these
      infants and report a treatment strategy.

PMID- 27889070
TI  - Prenatal ethanol exposure modifies locomotor activity and induces selective
      changes in Met-enk expression in adolescent rats.
AB  - Several studies suggest that prenatal ethanol exposure (PEE) facilitates ethanol
      intake. Opioid peptides play a main role in ethanol reinforcement during infancy
      and adulthood. However, PEE effects upon motor responsiveness elicited by an
      ethanol challenge and the participation of opioids in these actions remain to be
      understood. This work assessed the susceptibility of adolescent rats to prenatal
      and/or postnatal ethanol exposure in terms of behavioral responses, as well as
      alcohol effects on Met-enk expression in brain areas related to drug
      reinforcement. Motor parameters (horizontal locomotion, rearings and stereotyped
      behaviors) in pre- and postnatally ethanol-challenged adolescents were evaluated.
      Pregnant rats received ethanol (2g/kg) or water during gestational days 17-20.
      Adolescents at postnatal day 30 (PD30) were tested in a three-trial activity
      paradigm (habituation, vehicle and drug sessions). Met-enk content was
      quantitated by radioimmunoassay in several regions: ventral tegmental area [VTA],
      nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate
      putamen [CP], amygdala, hypothalamus and hippocampus. PEE significantly reduced
      rearing responses. Ethanol challenge at PD30 decreased horizontal locomotion and
      showed a tendency to reduce rearings and stereotyped behaviors. PEE increased Met
      enk content in the PFC, CP, hypothalamus and hippocampus, but did not alter
      peptide levels in the amygdala, VTA and NAcc. These findings suggest that PEE
      selectively modifies behavioral parameters at PD30 and induces specific changes
      in Met-enk content in regions of the mesocortical and nigrostriatal pathways, the
      hypothalamus and hippocampus. Prenatal and postnatal ethanol actions on motor
      activity in adolescents could involve activation of specific neural
      enkephalinergic pathways.

PMID- 27889069
TI  - Ru(III) anticancer agents with aromatic and non-aromatic dithiocarbamates as
      ligands: Loading into nanocarriers and preliminary biological studies.
AB  - Since the discovery of cisplatin in the 1960s, other metal complexes have been
      investigated as potential antitumor agents to overcome the side-effects
      associated with the administration of the Pt-based drug. In line with our
      previous research, in this work we report the synthesis and characterization of
      mono- and dinuclear Ru(III) complexes with the pyrrolidinedithiocarbamate (PDT)
      ligand and the more sterically-hindered carbazole-dithiocarbamato ligand (CDT),
      to compare their properties (both at the chemical and antiproliferative level),
      in an attempt to assess a structure-activity rationale. Moreover, to overcome the
      scarce solubility under physiological conditions of the Ru(III)-dithiocarbamato
      compounds, the biocompatible copolymer Pluronic(r) F127 has been used, to
      encapsulate the metal derivatives in water-soluble micellar carriers. Finally,
      preliminary biological evaluations on CDT and PDT compounds along with their
      nanoformulations, open intriguing perspectives in anticancer chemotherapy. In
      particular, comparing the structure of the Ru(III) derivatives, the ionic
      dinuclear PDT complex shows an important cytotoxic action in comparison to its
      neutral counterparts. Moreover, the micellar carrier improves the overall
      activity of the encapsulated Ru(III)-PDT chemotherapeutics. On the other hand,
      the nanoformulation of the CDT derivatives allows us to solubilize both the 1:3
      and the 2:5 complexes and to state their inactivity.

PMID- 27889071
TI  - Using X-Ray Crystallography to Simplify and Accelerate Biologics Drug
      Development.
AB  - Every major biopharmaceutical company incorporates a protein crystallography unit
      that is central to its structure-based drug discovery efforts. Yet these
      capabilities are rarely leveraged toward the formal higher order structural
      characterization that is so challenging but integral to large-scale biologics
      manufacturing. Although the biotech industry laments the shortcomings of its
      favored biophysical techniques, x-ray crystallography is not even considered for
      drug development. Why not? We suggest that this is due, at least in part, to
      outdated thinking (for a recent industry-wide survey, see Gabrielson JP, Weiss IV
      WF. Technical decision-making with higher order structure data: starting a new
      dialogue. J Pharm Sci. 2015;104(4):1240-1245). We examine some myths surrounding
      protein crystallography and highlight the inherent properties of protein crystals
      (molecular identity, biochemical purity, conformational uniformity, and
      macromolecular crowding) as having practicable commonalities with today's patient
      focused liquid drug products. In the new millennium, protein crystallography has
      become essentially a routine analytical test. Its application may aid the
      identification of better candidate molecules that are more amenable to high
      concentration processing, formulation, and analysis thereby helping to make
      biologics drug development quicker, simpler, and cheaper.

PMID- 27889072
TI  - If Euhydric and Isotonic Do Not Work, What Are Acceptable pH and Osmolality for
      Parenteral Drug Dosage Forms?
AB  - Parenteral products should aim toward being isotonic and euhydric (physiological
      pH). Yet, due to other considerations, this goal is often not reasonable or
      doable. There are no clear allowable ranges related to pH and osmolality, and
      thus, the objective of this review was to provide a better understanding of
      acceptable formulation pH, buffer strength, and osmolality taking into account
      the administration route (i.e., intramuscular, intravenous, subcutaneous) and
      administration technique (i.e., bolus, push, infusion). This evaluation was based
      on 3 different approaches: conventional, experimental, and parametric. The
      conventional way of defining formulation limits was based on standard pH and
      osmolality ranges. Experimental determination of titratable acidity or in vitro
      hemolysis testing provided additional drug product information. Finally, the
      parametric approach was based on the calculation of theoretical values such as
      (1) the maximal volume of injection which cannot shift the blood's pH or its
      molarity out of the physiological range and (b) a dilution ratio at the injection
      site and by verifying that threshold values are not exceeded. The combination of
      all 3 approaches can support the definition of acceptable pH, buffer strength,
      and osmolality of formulations and thus may reduce the risk of failure during
      preclinical and clinical development.

PMID- 27889073
TI  - Sources, composition and spatial distribution of marine debris along the
      Mediterranean coast of Israel.
AB  - Marine debris (litter) is a complex problem that affects human activities and the
      marine environment worldwide. The Clean Coast Program in Israel has had some
      success in keeping most of the coasts clean most of the time, but without
      understanding the mechanisms of accumulation of marine debris on the coasts of
      Israel. In 2012, we initiated a study to characterize the types of marine debris,
      its origins and spatial distribution. Nineteen surveys were done from June 2012
      to March 2015 on eight beaches that spanned the coast of Israel. Average debris
      density was 12.1 items per 100m2 and 90% of the items were plastic. The top
      debris categories were food wrappers and disposables, plastic bags and cigarette
      butts. However, there was variation in the top debris categories among the
      beaches indicating that a flexible approach with multiple options will be
      important when addressing the marine debris problem.

PMID- 27889074
TI  - Compositional shifts in bacterial communities associated with the coral Palythoa
      caribaeorum due to anthropogenic effects.
AB  - Corals harbor abundant and diverse prokaryotic communities that may be strongly
      influenced by human activities, which in turn compromise the normal functioning
      of coral species and predispose them to opportunistic infections. In this study,
      we investigated the effect of sewage dumping on the bacterial communities
      associated with the soft coral Palythoa caribaeorum at two sites in the Brazilian
      coast. We observed a dominance of bacterial species classified as human pathogens
      at sites exposed to untreated sewage discharge. The microbial diversity of
      undisturbed sites was more homogeneous and diverse and showed greater abundance.
      In addition, bacterial communities differed substantially between the exposed and
      undisturbed areas. The microbial community associated with the samples collected
      from the exposed sites revealed the anthropogenic effect caused by organic matter
      from untreated sewage dumping, with an abundance of pathogenic bacterial species.

PMID- 27889075
TI  - Abundance and composition of juvenile corals reveals divergent trajectories for
      coral assemblages across the United Arab Emirates.
AB  - Marked shifts in the composition of coral assemblages are occurring at many
      locations, but it is unknown whether these are permanent shifts reinforced by
      patterns of population replenishment. This study examined the composition of
      juvenile coral assemblages across the United Arab Emirates (UAE). Densities of
      juvenile corals varied significantly among locations, but were highest where
      coral cover was highest. Juvenile coral assemblages within the Persian Gulf were
      dominated by Porites, while no Acropora were recorded. We expect therefore,
      continued declines in Acropora abundance, while observed dominance of Porites is
      likely to persist. In the Oman Sea, Pocillopora was the dominant juvenile coral,
      with Acropora and Stylophora also recorded. This study shows that taxonomic
      differences in replenishment are reinforcing temporal shifts in coral composition
      within the southern Persian Gulf, but not in the Oman Sea. Differences in
      environmental conditions and disturbance regimes likely explain the divergent
      responses between regions.

PMID- 27889076
TI  - Impression technique for a complete-arch prosthesis with multiple implants using
      additive manufacturing technologies.
AB  - This article describes an impression technique for a complete-arch prosthesis
      supported by multiple implants where additive manufacturing technologies were
      used to fabricate a splinting framework and a custom tray. The technique
      presented uses a shim method to control the homogenous splinting acrylic resin
      and impression material during the procedure, thereby reducing laboratory and
      chairside time and the number of impression copings and laboratory analogs
      needed.

PMID- 27889077
TI  - [Sex education through popular education for health in a Brazilian rural social
      movement].
AB  - Based on the ideas of Paulo Freire, the methodological framework of Popular
      Education for Health (PEH) provides a more adaptable method for sex education,
      including societal participation as well as the social, historical and cultural
      dimensions of the population. The purpose of this work is to relate one such PEH
      experience in sex education, which took the form of a community project with a
      group of students from 10 to 28 years of age attending Itinerant Schools and with
      groups from the Landless Rural Workers Movement (MST) in the state of Parana,
      Brazil. This work provides knowledge of certain elements that may help in
      developing similar projects, not only for sex education but also education for
      other public health issues. PEH demonstrates a method of ensuring socially
      effective participation in the different dimensions of health-promotion
      strategies.

PMID- 27889078
TI  - Activities and geochronology of 137Cs in lake sediments resulting from sediment
      resuspension.
AB  - In lakes with a large surface area to watershed ratio 137Cs delivery is primarily
      by direct atmospheric fallout to the lake surface, where its activity in the
      sediments has been used to estimate the exposure to organisms and sediment mass
      deposition rates. Comparison of 137Cs in the historical atmospheric fallout
      record with 137Cs activity profiles in sediment cores reveals that although the
      general features of a maxima in the fallout deposition can be matched to activity
      peaks in the core, the general shape of the 137Cs profile is not an exact replica
      of the fallout history. Instead, the sediment reflects post-depositional
      processes such as resuspension, bioturbation, partitioning of 137Cs between the
      sediment solids and the pore fluids, and molecular diffusion of 137Cs through the
      pore fluids. Presented here is a model that couples these processes to a system
      time averaging (STA) model that accounts for the time history of 137Cs fallout
      and the particle residence time in the water column or in the 'active' surface
      sediment subject to resuspension. Sediment profiles are examined by comparing
      reasonable ranges of each of the coefficients of each of these major processes
      and by applying the model to cores collected from two large, shallow lakes, Lake
      Erie (USA/Canada) and Lake Winnipeg (Canada). The results indicate that the STA
      model with molecular diffusion and sediment resuspension best describes the data
      from these large, shallow lakes.

PMID- 27889079
TI  - Preface to a special issue "Japanese national mapping projects on large-scale
      environmental monitoring and mapping in Fukushima volume 2".

PMID- 27889080
TI  - Invasion Biology: Specific Problems and Possible Solutions.
AB  - Biological invasions have been unambiguously shown to be one of the major global
      causes of biodiversity loss. Despite the magnitude of this threat and recent
      scientific advances, this field remains a regular target of criticism - from
      outright deniers of the threat to scientists questioning the utility of the
      discipline. This unique situation, combining internal strife and an unaware
      society, greatly hinders the progress of invasion biology. It is crucial to
      identify the specificities of this discipline that lead to such difficulties. We
      outline here 24 specificities and problems of this discipline and categorize them
      into four groups: understanding, alerting, supporting, and implementing the
      issues associated with invasive alien species, and we offer solutions to tackle
      these problems and push the field forward.

PMID- 27889081
TI  - Complaints in long-term care facilities for older persons: Why residents do not
      give 'free advice'.
AB  - In health care policies, the right to complain is presented as a key patient
      right. Complaints are also seen as a potential vehicle for quality improvement.
      However, in long-term care facilities for older persons in the Netherlands,
      relatively few complaints are registered. An explorative qualitative study was
      performed at three long-term care facilities to examine the ways in which
      different relevant actors define and relate to complaints. We conducted
      observations and semi-structured interviews with 76 persons: residents, their
      family members, nurses, volunteers, middle (facility) and upper (institutional)
      managers and complaint handling personnel. Long-term care facilities are social
      contexts obeying complex social and cultural norms. There are great differences
      in how complaining and complaints are perceived. For most residents,
      'complaining' had strong negative connotations: they expected it would lead to
      undesirable social consequences that could not outweigh possible advantages. To
      nurses it was important to hear of residents' dissatisfactions but communicative
      aspects were challenging. Institutional managers saw complaints as 'free advice'
      they wished to use to enhance the quality of the care provision. Complaint
      managers underlined the procedural aspects to complaints. A more appropriate and
      productive policy on complaints in this health care sector should take these
      differences into account.

PMID- 27889082
TI  - NOD2 promotes cell proliferation and inflammatory response by mediating
      expression of TSLP in human airway smooth muscle cells.
AB  - The newly discovered intracytosolic pattern recognition receptor nucleotide
      binding oligomerization domain 2 (NOD2) has been studied as an important
      indicator of T helper 2 (Th2) inflammation, and its effect on regulatory T (Treg)
      cells is likely to modulate the immune response. In this study, we attempted to
      study the expression of NOD2 and its impact in human airway smooth muscle cells
      (HASMC). Quantitative real-time PCR (qRT-PCR) was used to measure the expression
      level of NOD2 in HASMC and comparisons were made between those from asthmatic and
      non-asthmatic donors; we found that NOD2 was significantly upregulated in asthma
      patient tissues and cell lines. In addition, overexpression of NOD2 apparently
      promotes cell proliferation and migration in HASMC. Gain-of-function in vitro
      experiments further showed that NOD2 overexpression significantly promotes pro
      inflammatory cytokine release in HASMC. Subsequent experimental analysis
      indicated that thymic stromal lymphopoietin (TSLP) is involved in NOD2-mediated
      cellular effects in HASMC. Therefore, our results indicate that NOD2 is an asthma
      related factor that can promote cell proliferation and inflammatory response by
      mediated expression of TSLP in HASMC. Taken together, our results indicate that
      NOD2 could serve as a potential diagnostic biomarker and therapeutic option for
      human asthma in the near future.

PMID- 27889083
TI  - Psychogenic Movement Disorders and Dopamine Transporter Scans: Still a Clinical
      Diagnosis?

PMID- 27889084
TI  - Linking Telomere Regulation to Stem Cell Pluripotency.
AB  - Embryonic stem cells (ESCs), somatic cell nuclear transfer ESCs, and induced
      pluripotent stem cells (iPSCs) represent the most studied group of PSCs.
      Unlimited self-renewal without incurring chromosomal instability and pluripotency
      are essential for the potential use of PSCs in regenerative therapy. Telomere
      length maintenance is critical for the unlimited self-renewal, pluripotency, and
      chromosomal stability of PSCs. While telomerase has a primary role in telomere
      maintenance, alternative lengthening of telomere pathways involving recombination
      and epigenetic modifications are also required for telomere length regulation,
      notably in mouse PSCs. Telomere rejuvenation is part of epigenetic reprogramming
      to pluripotency. Insights into telomere reprogramming and maintenance in PSCs may
      have implications for understanding of aging and tumorigenesis. Here, I discuss
      the link between telomere elongation and homeostasis to the acquisition and
      maintenance of stem cell pluripotency, and their regulatory mechanisms by
      epigenetic modifications.

PMID- 27889085
TI  - Impact of diurnal variability and meteorological factors on the PM2.5 - AOD
      relationship: Implications for PM2.5 remote sensing.
AB  - PM2.5 retrieval from space is still challenging due to the elusive relationship
      between PM2.5 and aerosol optical depth (AOD), which is further complicated by
      meteorological factors. In this work, we investigated the diurnal cycle of PM2.5
      in China, using ground-based PM measurements obtained at 226 sites of China
      Atmosphere Watch Network during the period of January 2013 to December 2015.
      Results showed that nearly half of the sites witnessed a PM2.5 maximum in the
      morning, in contrast to the least frequent occurrence (5%) in the afternoon when
      strong solar radiation received at the surface results in rapid vertical
      diffusion of aerosols and thus lower mass concentration. PM2.5 tends to peak
      equally in the morning and evening in North China Plain (NCP) with an amplitude
      of nearly twice or three times that in the Pearl River Delta (PRD), whereas the
      morning PM2.5 peak dominates in Yangtze River Delta (YRD) with a magnitude lying
      between those of NCP and PRD. The gridded correlation maps reveal varying
      correlations around each PM2.5 site, depending on the locations and seasons.
      Concerning the impact of aerosol diurnal variation on the correlation, the
      averaging schemes of PM2.5 using 3-h, 5-h, and 24-h time windows tend to have
      larger R biases, compared with the scheme of 1-h time window, indicating diurnal
      variation of aerosols plays a significant role in the establishment of explicit
      correlation between PM2.5 and AOD. In addition, high cloud fraction and relative
      humidity tend to weaken the correlation, regardless of geographical location.
      Therefore, the impact of meteorology could be one of the most plausible
      alternatives in explaining the varying R values observed, due to its non
      negligible effect on MODIS AOD retrievals. Our findings have implications for
      PM2.5 remote sensing, as long as the aerosol diurnal cycle, along with
      meteorology, are explicitly considered in the future.

PMID- 27889087
TI  - Characterisation of the phenanthrene degradation-related genes and degrading
      ability of a newly isolated copper-tolerant bacterium.
AB  - A copper-tolerant phenanthrene (PHE)-degrading bacterium, strain Sphingobium sp.
      PHE-1, was newly isolated from the activated sludge in a wastewater treatment
      plant. Two key genes, ahdA1b-1 encoding polycyclic aromatic hydrocarbon ring
      hydroxylating dioxygenase (PAH-RHDalpha) and xyLE encoding catechol-2,3
      dioxygenase (C23O), involved in the PHE metabolism by strain PHE-1 were
      identified. The PAH-RHD gene cluster showed 96% identity with the same cluster of
      Sphingomonas sp. P2. Our results indicated the induced transcription of xylE and
      ahdA1b-1 genes by PHE, simultaneously promoted by Cu(II). For the first time,
      high concentration of Cu(II) is found to encourage the expression of PAH-RHDalpha
      and C23O genes during PHE degradation. Applying Sphingomonas PHE-1 in PHE
      contaminated soils for bioaugmentation, the abundance of xylE gene was increased
      by the planting of ryegrass and the presence of Cu(II), which, in turn, benefited
      ryegrass growth. The best performance of PHE degradation and the highest
      abundance of xylE genes occurred in PHE-copper co-contaminated soils planted with
      ryegrass.

PMID- 27889086
TI  - Impacts of regional transport on black carbon in Huairou, Beijing, China.
AB  - The 22nd Asia-Pacific Economic Cooperation (APEC) Conference was held near Yanqi
      Lake, Huairou, in Beijing, China during November 10-11, 2014. To guarantee haze
      free days during the APEC Conference, the Beijing government and the governments
      of the surrounding provinces implemented a series of controls. Three months of
      Aethalometer 880 nm black carbon (BC) measurements were examined to understand
      the hourly fluctuations in BC concentrations that resulted from emission controls
      and meteorology changes. Measurements were collected at the University of Chinese
      Academy of Sciences near the APEC Conference site and in Central Beijing at the
      Institute of Remote Sensing and Digital Earth of the Chinese Academy of Sciences.
      Synoptic conditions are successfully represented through analysis of backward
      trajectories in six cluster groups. The clusters are identified based on air mass
      transport from various areas such as Inner Mongolia, Russia, three northeastern
      provinces, and Hebei industrial areas, to the measurement sites. Air pollution
      control measures during the APEC Conference significantly reduced BC at the
      conference site (Huairou) and in Central Beijing, with greater reductions in BC
      concentrations at the conference site than in Central Beijing. The highest BC
      concentrations in Huairou were associated with air masses originating from
      Central Beijing rather than from the Hebei industrial region. The success of the
      control measures implemented in Beijing and the surrounding regions demonstrates
      that BC concentrations can be effectively reduced to protect human health and
      mitigate regional climate forcing. This study also demonstrates the need for
      regional strategies to reduce BC concentrations, since urban areas like Beijing
      are sources as well as downwind receptors of emissions.

PMID- 27889088
TI  - Osteoblast cellular activity on low elastic modulus Ti-24Nb-4Zr-8Sn alloy.
AB  - OBJECTIVES: Low modulus beta-titanium alloys with non-toxic alloying elements are
      envisaged to provide good biocompatibility and alleviate the undesired stress
      shielding effect. The objective of this study is to fundamentally elucidate the
      biological response of novel high strength-low elastic modulus Ti2448 alloy
      through the study of bioactivity and osteoblast cell functions. METHODS:
      Characterization techniques such as SEM, EDX, XRD, and fluorescence microscopy
      were utilized to analyze the microstructure, morphology, chemical composition,
      and cell adhesion. The cellular activity was explored in terms of cell-to-cell
      communication involving proliferation, spreading, synthesis of extracellular and
      intracellular proteins, differentiation, and mineralization. RESULTS: The
      formation of fine apatite-like crystals on the surface during immersion test in
      simulated body fluid confirmed the bioactivity of the surface, which provided the
      favorable osteogenic microenvironment for cell-material interaction. The
      proliferation and differentiation of pre-osteoblasts and their ability to form a
      well mineralized bone-like extracellular matrix (ECM) by secreting bone markers
      (ALP, calcium, etc.) over the surface point toward the determining role of unique
      surface chemistry and surface properties of the Ti-24Nb-4Zr-8Sn (Ti2448) alloy in
      modulating osteoblasts functions. SIGNIFICANCE: These results demonstrated that
      the low modulus (~49GPa) Ti2448 alloy with non-toxic alloying elements can be
      used as a potential dental or orthopedic load-bearing implant material.

PMID- 27889089
TI  - Susceptible vessel sign: identification of arterial occlusion and clinical
      implications in acute ischaemic stroke.
AB  - AIM: To determine the accuracy of the susceptible vessel sign (SVS) in the
      detection of arterial occlusion and its clinical implication in acute ischaemic
      stroke. MATERIALS AND METHODS: Consecutive ischaemic stroke patients who
      underwent magnetic resonance imaging (MRI) with susceptibility-weighted imaging
      (SWI) within 24 hours of symptom onset or time last-seen-well were included. Two
      independent neuroradiologists reviewed the SWI for evidence of the SVS. Admission
      stroke severity was determined by the National Institute of Health Stroke Scale
      (NIHSS) scores, and poor clinical outcome was defined by a 3-months modified
      Rankin scale (mRS) score >2. RESULTS: The SVS was identified in 26 (12%) of 213
      patients with substantial inter-reviewer agreement. The SVS had 99% specificity,
      88% negative predictive value (NPV), 51% sensitivity, and 92% positive predictive
      value (PPV) for detection of acute arterial occlusions. In consecutive stroke
      patients, the presence of SVS was associated with higher admission NIHSS scores
      (median 9 versus 3, p<0.001), arterial occlusion (92% versus 12%, p<0.001),
      larger infarct volume (162+/-180 ml versus 25+/-48 ml, p=0.001), and higher rate
      of poor clinical outcome at 3-months follow-up (58% versus 25%, p=0.001). In the
      subset of patients with acute arterial occlusion (n=47), the SVS was associated
      with higher admission NIHSS scores (median of 10 versus 3, p=0.038) and larger
      infarct volumes (173+/-184 ml versus 76+/-112 ml, p=0.034). CONCLUSIONS: The SVS
      is a highly specific sign of occlusive arterial thrombus, and is associated with
      larger infarct volume and more severe presentation in a series of consecutive
      stroke patients, as well as in the subgroup of patients with acute arterial
      occlusion.

PMID- 27889090
TI  - Focal nodular and diffuse haematopoietic marrow hyperplasia in patients with
      underlying malignancies: a radiological mimic of malignancy in need of
      recognition.
AB  - AIM: To report the authors' experience of focal nodular haematopoietic marrow
      hyperplasia (FNHMH) and diffuse haematopoietic marrow hyperplasia (DHMH)
      clinically masquerading as skip, distant, or disseminated metastasis in seven
      patients with underlying malignant neoplasms. MATERIALS AND METHODS: Five
      patients with FNHMH and two with DHMH mistaken radiologically as skip and
      disseminated metastasis, respectively, were compared and contrasted with four
      patients with osteosarcomas and two with chondrosarcomas harbouring skip
      metastasis, noting the temporal relationship with their haematological profile.
      RESULTS: FNHMH and DHMH were undetectable by plain radiography and computed
      tomography (CT) except one showing subtle sclerosis on CT. They showed either
      isointense or hyperintense, but not hypointense, attenuation at T1-weighted
      imaging, and all showed hyperintense attenuation at T2-weighted MRI relative to
      skeletal muscle. Of the five patients who underwent bone scintigraphy, one showed
      mildly increased uptake, and one out of two showed markedly increased 2-[18F]
      fluoro-2-deoxy-d-glucose (FDG)-positron-emission tomography (PET) uptake. The
      rates for sarcoma skip metastasis by plain radiography, CT, MRI, and bone
      scintigraphy were 40%, 66.7%, 100%, and 66.7%, respectively. At MRI, 60% showed
      hypointense and 40% isointense attenuation at T1-weighted, 80% hyperintense and
      20% hypointense attenuation at T2-weighted imaging. Combined FDG-PET and CT,
      which was performed in only one patient, failed to show the skip metastasis. Not
      every patient with FNHMH or DHMH received granulocyte colony-stimulating factor
      (GCSF), but all had low or falling haemoglobin levels, which may thus be the
      prime cause for HMH. CONCLUSIONS: Due to overlapping radiological features, FNHMH
      and DHMH are great radiological mimics of malignancy. In some cases, needle
      biopsy is required for their definitive differentiation.

PMID- 27889091
TI  - Breath-hold PET/CT-guided tumour ablation under general anaesthesia: accuracy of
      tumour image registration and projected ablation zone overlap.
AB  - AIM: To assess single-breath-hold combined positron-emission tomography/computed
      tomography (PET/CT) for accuracy of tumour image registration and projected
      ablation volume overlap in patients undergoing percutaneous PET/CT-guided tumour
      ablation procedures under general anaesthesia. MATERIALS AND METHODS: Eight
      patients underwent 12 PET/CT-guided tumour-ablation procedures to treat 20
      tumours in the lung, liver, or adrenal gland. Using breath-hold PET/CT, the
      centre of the tumour was marked on each PET and CT acquisition by four readers to
      assess two- (2D) and three-dimensional (3D) spatial misregistration. Overlap of
      PET and CT projected ablation volumes were compared using the Dice similarity
      coefficient (DSC). Interobserver differences were assessed with repeated measure
      analysis of variance (ANOVA). Technical success and local progression rates were
      noted. RESULTS: Mean tumour 2D PET/CT misregistrations were 1.02 mm (range 0.01
      5.02), 1.89 (0.03-7.85), and 3.05 (0-10) in the x, y, and z planes. Mean 3D
      misregistration was 4.4 mm (0.36-10.74). Mean projected PET/CT ablation volume
      DSC was 0.72 (+/-0.19). No significant interobserver differences in 3D
      misregistration (p=0.73) or DSC (p=0.54) were observed. Technical success of
      ablations was 100%; one (5.3%) of 19 tumours progressed. CONCLUSION: Accurate
      spatial registration of tumours and substantial overlap of projected ablation
      volumes are achievable when comparing PET and CT acquisitions from single-breath
      hold PET/CT. The results suggest that tumours visible only at PET could be
      accurately targeted and ablated using this technique.

PMID- 27889092
TI  - Current Quality Measurement Tools Are Insufficient to Assess Complications in
      Orthopedic Surgery.
AB  - PURPOSE: The American College of Surgeons National Surgical Quality Improvement
      Project (ACS-NSQIP) is a clinically-derived, validated tool to track outcomes in
      surgery. The Agency for Healthcare Research and Quality Patient Safety Indicators
      (AHRQ-PSI) are a set of computer algorithms run on administrative data to
      identify adverse events. The purpose of this study is to compare complications
      following orthopedic surgery identified by ACS-NSQIP and AHRQ-PSI. METHODS:
      Patients between 2010 and 2012 who underwent orthopedic procedures (arthroplasty,
      spine, trauma, foot and ankle, hand, and upper extremity) at our tertiary-care,
      academic institution were identified (n = 3,374). Identification of inpatient
      adverse events by AHRQ-PSI in the cohort was compared with 30-day events
      identified by ACS-NSQIP. Adverse events common to both AHRQ-PSI and ACS-NSQIP
      were infection, sepsis, venous thromboembolism, bleeding, respiratory failure,
      wound disruption, and renal failure. Concordance between AHRQ-PSI and ACS-NSQIP
      for identifying adverse events was examined. RESULTS: A total of 729 adverse
      events (21.6%) were identified in the cohort using ACS-NSQIP methodology and 35
      adverse events (1.0%) were found using AHRQ-PSI. Only 12 events were identified
      by both methodologies. The most common complication was bleeding in ACS-NSQIP
      (18.1%) and respiratory failure in AHRQ-PSI (0.53%). The overlap was highest for
      venous thromboembolic events. There was no overlap in adverse events for 5 of the
      7 categories of adverse events. CONCLUSIONS: A large discrepancy was observed
      between adverse events reported in ACS-NSQIP and AHRQ-PSI. A large percentage of
      clinically important adverse events identified in ACS-NSQIP were missed in AHRQ
      PSI algorithms. The ability of AHRQ-PSI for detecting adverse events varied
      widely with ACS-NSQIP. CLINICAL RELEVANCE: AHRQ-PSI algorithms currently are
      insufficient to assess the quality of orthopedic surgery.

PMID- 27889093
TI  - Removal of a Contraceptive Implant From the Brachial Neurovascular Sheath.
AB  - Subdermal implantable devices are commonly used for long-acting contraception in
      the United States and Europe. Although relatively safe in nature, their
      implantation and removal may be associated with potential complications, some of
      which may require surgical intervention. Complications may include infection,
      incorrect implantation, migration, or difficulty with removal. Proximal migration
      has been reported; however, there are no reports of devices that have migrated
      within the brachial neurovascular sheath. This case report describes migration of
      an implantable contraceptive within the brachial neurovascular sheath that
      required surgical removal.

PMID- 27889094
TI  - A proposal of an effective coping approach to esophageal intubation.

PMID- 27889095
TI  - Continuous insufflation of oxygen without endotracheal intubation improves
      cardiopulmonary resuscitation, a manikin-based model.

PMID- 27889097
TI  - Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates
      Expression of Pro- and Anti-degenerative Factors.
AB  - Developmental neuronal cell death and axonal elimination are controlled by
      transcriptional programs, of which their nature and the function of their
      components remain elusive. Here, we identified the dual specificity phosphatase
      Dusp16 as part of trophic deprivation-induced transcriptome in sensory neurons.
      Ablation of Dusp16 enhanced axonal degeneration in response to trophic
      withdrawal, suggesting that it has a protective function. Moreover, axonal skin
      innervation was severely reduced while neuronal elimination was increased in the
      Dusp16 knockout. Mechanistically, Dusp16 negatively regulates the transcription
      factor p53 and antagonizes the expression of the pro-degenerative factor, Puma
      (p53 upregulated modulator of apoptosis). Co-ablation of Puma with Dusp16
      protected axons from rapid degeneration and specifically reversed axonal
      innervation loss early in development with no effect on neuronal deficits.
      Overall, these results reveal that physiological axonal elimination is regulated
      by a transcriptional program that integrates regressive and progressive elements
      and identify Dusp16 as a new axonal preserving factor.

PMID- 27889098
TI  - Reply for comment on "Adsorptive removal of methylene blue by rhamnolipid
      functionalized graphene oxide from wastewater".

PMID- 27889096
TI  - Novel Functional Properties of Drosophila CNS Glutamate Receptors.
AB  - Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect
      genomes, suggesting conserved functional properties corresponding to their
      vertebrate counterparts. However, heterologous expression of the Drosophila
      kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand
      selectivity at odds with the classification used for vertebrate glutamate
      receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and
      desensitizing receptor that is inhibited by both NMDA and the NMDA receptor
      antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that
      these ligands stabilize open cleft conformations, explaining their action as
      antagonists. Surprisingly, the AMPA receptor DGluR1A shows weak activation by its
      namesake agonist AMPA and also by quisqualate. Crystallization of the DGluR1A
      ligand-binding domain reveals amino acid exchanges that interfere with binding of
      these ligands. The unexpected ligand-binding profiles of insect iGluRs allows
      classical tools to be used in novel approaches for the study of synaptic
      regulation. VIDEO ABSTRACT.

PMID- 27889099
TI  - Eating disorders in the context of preconception care: fertility specialists'
      knowledge, attitudes, and clinical practices.
AB  - OBJECTIVE(S): To gauge fertility specialists' knowledge, clinical practices, and
      training needs in regard to eating disorders. DESIGN: Cross-sectional study.
      SETTINGS: Fertility clinics. PARTICIPANTS: Eighty Australian and New Zealand
      fertility specialists who were members of the Fertility Society of Australia.
      INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Responses to an anonymously
      completed online questionnaire. RESULT(S): Approximately 54% of doctors correctly
      identified the body mass index relevant to anorexia nervosa, and 30% identified
      menstrual disturbances for anorexia, while 63.8% of doctors incorrectly nominated
      maladaptive weight control behaviors as a characteristic of binge eating
      disorder. While clinicians (83.7%) agreed it was important to screen for eating
      disorders during preconception assessments, 35% routinely screened for eating
      disorders and 8.8% indicated that their clinics had clinical practice guidelines
      for management of eating disorders. A minority of participants (13.8%) felt
      satisfied with their level of university training in eating disorders, 37.5% of
      doctors felt confident in their ability to recognize symptoms of an eating
      disorder, and 96.2% indicated a need for further education and clinical
      guidelines. On most items examined, knowledge and clinical practices regarding
      eating disorders did not differ according to doctor gender or years of clinical
      experience working as a fertility specialist. CONCLUSION(S): Knowledge about
      eating disorders in the context of fertility treatment is important. This study
      highlights the uncertainty among fertility specialists in detecting features of
      eating disorders. The findings point to the importance of further education and
      training, including the development of clinical guidelines specific to fertility
      health care providers.

PMID- 27889100
TI  - Epigenetic regulation of an adverse metabolic phenotype in polycystic ovary
      syndrome: the impact of the leukocyte methylation of PPARGC1A promoter.
AB  - OBJECTIVE: To investigate PPARGC1A promoter methylation and mitochondria DNA
      (mtDNA) content in the leukocytes of women with polycystic ovary syndrome (PCOS)
      and analyze the relationship between these indices and metabolic risk for women
      with PCOS. DESIGN: Cross-sectional study. SETTING: University hospital.
      PATIENT(S): A total of 175 women with PCOS and 127 healthy controls.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Women with and without PCOS
      classified using the typical metabolic risk criteria of the National Cholesterol
      Education Program's Adult Treatment Panel III report (ATPIII), methylation of
      PPARGC1A promoter tested by methylation-specific polymerase chain reaction, and
      mtDNA content confirmed by quantitative polymerase chain reaction (PCR).
      RESULT(S): PPARGC1A promoter methylation was specifically increased, but mtDNA
      content was specifically decreased in women with PCOS compared with the control
      women after adjustment for body mass index. Moreover, in women with PCOS who have
      increased metabolic risk, the differences in PPARGC1A promoter methylation and
      mitochondrial content were aggravated. CONCLUSION(S): In conclusion, PPARGC1A
      promoter methylation and mitochondrial content were found to be potential
      biomarkers for the prediction of metabolic risk in women with PCOS.

PMID- 27889102
TI  - Analysis of gene expression and regulation implicates C2H9orf152 has an important
      role in calcium metabolism and chicken reproduction.
AB  - The reproductive system of a female bird is responsible for egg production. The
      genes highly expressed in oviduct are potentially important. From RNA-seq
      analysis, C2H9orf152 (an orthologous gene of human C9orf152) was identified as
      highly expressed in chicken uterus. To infer its function, we obtained and
      characterized its complete cDNA sequence, determined its spatiotemporal
      expression, and probed its transcription factor(s) through pharmaceutical
      approach. Data showed that the complete cDNA sequence was 1468bp long with a
      789bp of open reading frame. Compared to other tested tissues, this gene was
      highly expressed in the oviduct and liver tissues, especially uterus. Its
      expression in uterus was gradually increased during developmental and
      reproductive periods, which verified its involvement in the growth and maturity
      of reproductive system. In contrast, its expression was not significant different
      between active and quiescent uterus, suggesting the role of C2H9orf152 in
      reproduction is likely due to its long-term effect. Moreover, based on its 5'
      flanking sequence, Foxd3 and Hnf4a were predicted as transcription factors of
      C2H9orf152. Using berberine or retinoic acid (which can regulate the activities
      of Hnf4a and Foxd3, respectively), we demonstrated suppression of C2H9orf152 by
      the chemicals in chicken primary hepatocytes. As retinoic acid regulates calcium
      metabolism, and Hnf4a is a key nuclear factor to liver, these findings suggest
      that C2H9orf152 is involved in liver function and calcium metabolism of
      reproductive system. In conclusion, C2H9orf152 may have a long-term effect on
      chicken reproductive system by regulating calcium metabolism, suggesting this
      gene has an important implication in the improvement of egg production and
      eggshell quality.

PMID- 27889101
TI  - Highly heterogeneous genomic landscape of uterine leiomyomas by whole exome
      sequencing and genome-wide arrays.
AB  - OBJECTIVE: To determine the genomic signatures of human uterine leiomyomas and
      prevalence of MED12 mutations in human uterine leiomyosarcomas. DESIGN:
      Retrospective cohort study. SETTING: Not applicable. PATIENT(S): This study
      included a set of 16 fresh frozen leiomyoma and corresponding unaffected
      myometrium specimens as well as 153 leiomyosarcomas collected from women
      diagnosed with uterine leiomyomas or leiomyosarcomas who underwent clinically
      indicated abdominal hysterectomy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Whole exome sequencing and high-resolution X-chromosome and whole genome single
      nucleotide polymorphism microarray analyses were performed on leiomyoma samples
      negative for the known MED12 mutations and compared with their corresponding
      myometrium. Leiomyosarcoma specimens were examined for exon 2 MED12 mutations to
      evaluate the frequency of MED12 mutated leiomyosarcomas. RESULT(S): Our results
      indicate remarkable genomic heterogeneity of leiomyoma lesions. MED12-negative
      leiomyomas contain copy number alterations involving the Mediator complex
      subunits such as MED8, MED18, CDK8, and long intergenic nonprotein coding RNA340
      (CASC15), which may affect the Mediator architecture and/or its transcriptional
      activity. We also identified mutations in a number of genes that were implicated
      in leiomyomagenesis such as COL4A6, DCN, and AHR, as well as novel genes: NRG1,
      ADAM18, HUWE1, FBXW4, FBXL13, and CAPRIN1. CONCLUSION(S): Mutations in genes
      implicated in cell-to-cell interactions and remodeling of the extracellular
      matrix and genomic aberrations involving genes coding for the Mediator complex
      subunits were identified in uterine leiomyomas. Additionally, we discovered that
      ~4.6% of leiomyosarcomas harbored MED12 exon 2 mutations, but the relevance of
      this association with molecular pathogenesis of leiomyosarcoma remains unknown.

PMID- 27889103
TI  - Cardiac Autonomic Changes After Thoracic Sympathectomy: A Prospective, Randomized
      Study.
AB  - BACKGROUND: We evaluated whether cardiac autonomic changes could be associated
      with different extent of sympathetic nerve resection in the management of
      essential palmar hyperhidrosis. METHODS: Sixty patients with essential palmar
      hyperhidrosis were randomly allocated to undergo excision of T3 ganglia
      (sympathicectomy group; n = 30) or to interruption of sympathetic chain at the T2
      to T3 level with ganglion sparing (sympathicotomy group; n = 30). Time and
      frequency domains were measured with a 24-Holter monitor during daytime,
      nighttime, and 24-hour periods at different interval points (7 days before
      operation; 24 hours; and 1, 3, and 6 months later), and the differences were
      statistically compared. Clinical outcomes were also evaluated. RESULTS: Twenty
      eight of 30 patients of the sympathectomy and 29 of 30 patients of the
      sympathicotomy group completed the study. In both groups, we observed a
      significant increase (p < 0.05) of vagal activity measurements as root mean
      square of the successive differences of heart period; proportion of adjacent
      normal R-R intervals >50 ms; high frequency; and a significant decrease (p <
      0.05) of adrenergic activity variables as heart rate, low frequency, and the
      ratio between low frequency and high frequency during daytime, nighttime, and 24
      hour periods. These changes were significantly more evident (p < 0.05) in the
      sympathectomy group than in the sympathicotomy group. Clinical outcomes were
      similar between the two groups. CONCLUSIONS: Endoscopic thoracic sympathectomy
      caused a shift of sympathovagal balance toward parasympathetic tone that seems to
      be associated with the extent of denervation. This trial was registered at
      clinicaltrials.gov as NCT02733497.

PMID- 27889104
TI  - Three-dimensional reconstruction of the embryonic pancreas in the grass snake
      Natrix natrix L. (Lepidosauria, Serpentes) based on histological studies.
AB  - The aim of this study was to evaluate two research hypotheses: H0-the embryonic
      pancreas in grass snakes develops in the same manner as in all previously
      investigated amniotes (from three buds) and its topographical localization within
      the adult body has no relation to its development; H1-the pancreas develops in a
      different manner and is related to the different topography of internal organs in
      snakes. For the evaluation of these hypotheses we used histological methods and
      three-dimensional (3D) reconstructions of the position of the pancreatic buds and
      surrounding organs at particular developmental stages and of the final position
      and shape of the pancreatic gland. Our results indicate that the pancreas
      primordium in the grass snake is formed by only two buds - a dorsal and a ventral
      one - that are not connected until the end of stage II. This differs from the
      majority of vertebrates investigated so far. The gall bladder of the grass snake
      embryos is connected with the liver only by a thin cystic duct, which also
      differs from many other vertebrates. Our histological study also indicates a
      different distribution of the endocrine cells in the embryonic pancreas of the
      grass snake because the first endocrine cells appeared in the dorsal part of the
      pancreas in a region located close to the spleen. During the entire developmental
      period no evidence of these cells was found in the ventral part of the pancreas.
      The endocrine cells form elongated, large and irregular-shaped islets. They can
      also form structures resembling "inverted acini". Such an arrangement is
      characteristic of snakes only. The differentiating pancreas penetrates the
      ventral part of the developing spleen and divides it into three separate parts at
      developmental stage IX. This is unique among vertebrates. At the end of the
      embryonic development (stage XI), the pancreas, the spleen and the gall bladder
      are located in close proximity and form the so-called triad. Our results suggest
      that the untypical topography of the organ systems in snakes may determine the
      unique development of the pancreas in these animals.

PMID- 27889105
TI  - Corrigendum to "Methylene blue staining in the parotid surgery: Randomized trial,
      144 patients" [Am J Otolaryngol 37 (2016) 22-26].

PMID- 27889106
TI  - Expression of the JAK/STAT signaling pathway in the ligamentum flavum of patients
      with lumbar spinal canal stenosis.
AB  - BACKGROUND: Ligamentum flavum (LF) hypertrophy is an important cause of lumbar
      spinal canal stenosis (LSS), one of the most common spinal disorders in the
      elderly. Although many cytokines are reported to be associated with LF
      hypertrophy, the intracellular signaling system is rarely discussed. The purpose
      of this study was to identify the JAK/STAT signaling pathway and to examine the
      role of the JAK/STAT systems in the hypertrophied LF. METHODS: The LF of 10 LSS
      patients was analyzed and the expression of JAK1, STAT3, phosphorylated (p)
      STAT3, and actin was examined by Western blot analysis. The expression of p-STAT3
      was also examined by immunostaining and its positive cell ratio was compared
      between LSS and non-LSS samples. We measured the thickness of the LF on magnetic
      resonance images and studied the relationship between its thickness and the
      expression of p-STAT3. RESULTS: JAK1, STAT3, and p-STAT3 were detected in almost
      all samples by Western blot analysis. Immunoreactivity against p-STAT3 was
      observed mainly in endothelial- and fibroblast-like cells. The expression of p
      STAT3 was significantly higher in LSS than non-LSS samples; it was significantly
      stronger on the dorsal than the dural side of the LF and positively correlated
      with the thickness of the LF on the dorsal side. CONCLUSIONS: The JAK/STAT
      signaling pathway is positively correlated with the thickness of the LF. Our
      findings suggest that JAK1 and STAT3 molecules are involved in and regulate LF
      hypertrophy.

PMID- 27889107
TI  - Combination of the anthocyanidins malvidin and peonidin attenuates
      lipopolysaccharide-mediated inflammatory gene expression in primary human
      adipocytes.
AB  - We recently demonstrated that California table grapes and a methanol-extractable,
      polyphenol-rich fraction decreased adiposity, insulin resistance, or markers of
      inflammation in high-fat fed mice. Malvidin and peonidin glycosides were the 2
      most abundant anthocyanins in the polyphenol-rich fraction. We hypothesized that
      a blood borne combination of anthocyanidins malvidin and peonidin derived from
      intestinal beta-glycosidase metabolism of these 2 anthocyanins are responsible,
      in part, for the beneficial health effects observed in vivo. Therefore, we
      supplemented primary human adipocytes with malvidin or peonidin, alone or
      together, followed by acute lipopolysaccharide (LPS) treatment. Neither peonidin
      nor malvidin alone consistently decreased the expression of several inflammatory
      genes. However, supplementing adipocytes with an equal combination of malvidin
      plus peonidin followed by LPS treatment decreased the mRNA levels of interleukin
      (IL)-6, IL-1beta, IL-8, monocyte chemoattractant protein-1, toll-like receptor-2,
      tumor necrosis factor alpha, cyclooxygenase-2, and interferon gamma-induced
      protein-10. The highest combination dose of malvidin plus peonidin decreased or
      increased the expression of protein tyrosine phosphatase-1B and hormone sensitive
      lipase, respectively, genes encoding proteins associated with insulin resistance
      or lipolysis. These data indicate that a combination of malvidin plus peonidin
      have potentiating interactions that reduce inflammatory gene expression; however,
      in vivo studies are needed to support these in vitro data.

PMID- 27889109
TI  - A cross-sectional study of the impact of physiotherapy and self directed exercise
      on the functional outcome of internally fixed isolated unimalleolar Weber B ankle
      fractures.
AB  - This study aimed to measure the functional outcome and quality of life in a group
      of patients with the same fracture type (unimalleolar Weber B ankle fractures)
      treated operatively at various time points and to explore the determinants of
      such outcomes. A cross-sectional retrospective population study was conducted.
      Validated Patient Related Outcome Measures (PROMs) and patient interviews were
      used. Fifty-one patients were included with a mean age of 54.9 years. Mean follow
      up was 25 months (range 4-46 months). Mean functional scores were high (mean
      AOFAS 79.2, O&M 75.7, VAS-FA 80.5). However, 32% of patients did not classify
      themselves as fully recovered during interviews. Patient reported self-directed
      exercise had a statistically significant positive effect on self-reported patient
      perceptions of outcome (p=0.022) and PROMs (AOFAS p=0.01, O&M p=0.016, VAS-FA
      p=0.011). Formal physiotherapy rehabilitation was found to have no effect on self
      reported patient perceptions (p=0.242) or PROMs (AOFAS p=0.8, O&M p=0.73, VAS-FA
      p=0.46). Our finding that physical activity is associated with improved outcome
      would suggest structured exercise programmes should be considered in place of
      physiotherapy to optimise patient outcomes.

PMID- 27889108
TI  - Positive Regulation of Lyn Kinase by CD148 Is Required for B Cell Receptor
      Signaling in B1 but Not B2 B Cells.
AB  - B1 and B2 B cells differ in their ability to respond to T-cell-independent (TI)
      antigens. Here we report that the Src-family kinase (SFK) regulator CD148 has a
      unique and critical role in the initiation of B1 but not B2 cell antigen receptor
      signaling. CD148 loss-of-function mice were found to have defective B1 B-cell
      mediated antibody responses against the T-cell-independent antigens NP-ficoll and
      Pneumovax 23 and had impaired selection of the B1 B cell receptor (BCR)
      repertoire. These deficiencies were associated with a decreased ability of B1 B
      cells to induce BCR signaling downstream of the SFK Lyn. Notably, Lyn appeared to
      be selectively regulated by CD148 and loss of this SFK resulted in opposite
      signaling phenotypes in B1 and B2 B cells. These findings reveal that the
      function and regulation of Lyn during B1 cell BCR signaling is distinct from
      other B cell subsets.

PMID- 27889110
TI  - Psychological distress and physical disability in patients sustaining severe
      injuries in road traffic crashes: Results from a one-year cohort study from three
      European countries.
AB  - The current study aimed to follow-up a group of road crash survivors for one year
      and assesses the impact of injury on their psychological and physical condition.
      All crash survivors that were admitted to the intensive or sub-intensive care
      units of selected hospitals in Greece, Germany and Italy over one year period
      (2013-2014), were invited to participate in the study and were interviewed at
      three different time-points as follows: (a) at one month (baseline data), (b) at
      six months, and (c) at twelve months. The study used widely recommended
      classifications for injury severity (AIS, MAIS) and standardized health outcome
      measures such as the Disability Assessment Schedule II (WHODAS 2.0) to measure
      disability, "Impact of Event Scale" (IES-R) to measure Post-Traumatic Stress
      Disorder (PTSD), Center for Epidemiological Studies Depression Scale (CES-D
      Scale) to measure depression. A total of 120 patients were enrolled in the study
      in all the partner countries and 93 completed all follow up questionnaires. The
      risk of physical disability was 4.57 times higher [CI 1.98-2.27] at the first
      follow up and 3.43 times higher [CI 1.43-9.42] at the second follow up as
      compared with the time before the injury. There was a 79% and an 88% lower risk
      of depression at the first and the second follow up respectively, as compared
      with the baseline time. There was also a 72% lower risk of Post-Traumatic Stress
      at the second follow up as compared with the baseline time. A number of factors
      relevant to the individuals, the road crash and the injury, were shown to
      distinguish those at higher risk of long-lasting disability and psychological
      distress including age, marital status, type of road user, severity and type of
      the injury, past emotional reaction to distress. The study highlights the
      importance of a comprehensive and holistic understanding of the impact of injury
      on an individual and further underlines the importance of screening and treating
      psychological comorbidities in injury in a timely manner.

PMID- 27889111
TI  - Minimally invasive fixation in tibial plateau fractures using an pre-operative
      and intra-operative real size 3D printing.
AB  - The purpose of our study was to compare the outcome after minimally invasive
      reconstruction and internal fixation with and without the use of pre- and intra
      operative real size 3D printing for patients with displaced tibial plateau
      fractures (TPFs). We prospectively followed up 40 consecutive adult patients with
      closed TPF who underwent surgical treatment of reconstruction of the tibial
      plateau with the use of minimally invasive fixation. Sixteen patients (group 1)
      were operated using a pre-operative and intra-operative real size 3D-model, while
      24 patients (group 2) were operated without 3D-model printing, but using only pre
      operative and intra-operative 3D Tc-scan images. The mean operating time was
      148.2+/-15.9min for group 1 and 174.5+/-22.2min for group 2 (p=0.041). In
      addition, the mean intraoperative blood loss was less in group 1 (520mL) than in
      group 2 (546mL) (p=0.534). After discharge, all patients were followed up at 6
      weeks, 12 weeks, 6 months, 1year and then every year post surgically and
      radiographic evaluation was carried out each time using clinical and radiological
      Rasmussen's score, with no significant differences between the two groups. Two
      patients (group 2) developed infection which resolved within 3 weeks after usage
      of antibiotics. Neither superficial nor deep infections were present in group 1.
      In all patients, no non-union occurred. No intraoperative, perioperative, or
      postoperative complications, such as loss of valgus correction, bone fractures,
      or metallic plate failures were detected at follow-up. In patients operated with
      the use of 3D-model printing, we found a significant reduction in surgical time.
      Moreover, the technique without a 3D-model increased the patient's and the
      surgeon's exposure to radiation.

PMID- 27889113
TI  - Editorial overview: Multi-protein assemblies in signaling.

PMID- 27889112
TI  - Risk factors for cut-out of double lag screw fixation in proximal femoral
      fractures.
AB  - OBJECTIVE: We assessed factors associated with cut-out after internal fixation of
      proximal femoral fractures using double lag screw nails. DESIGN: Retrospective
      cohort study. SETTING: A university hospital. PATIENTS AND METHODS: Patients with
      non-pathological intertrochanteric femur fractures and a minumum 90days follow-up
      who underwent internal fixation with dual lag screw nails were included.
      Potential risk factors for lag screw cut-out investigated by our study were: age,
      gender, body mass index, comorbidities (American Society of Anesthesiologists
      [ASA] classification), type of fracture (AO/OTA classification), fracture
      stability, side, operation time, implant length, reduction quality, tip-apex
      distance (TAD), and lag screw configuration. Logistic regression was used to
      investigate potential predictors of screw cut-out. RESULTS: Eighty-five of the
      118 patients with hip fractures treated between February 2010 and November 2013
      at our institution met the inclusion criteria for the study. Fifty-eight patients
      were female (68.2%), mean age was 77.4 (range: 50-95 years), mean follow up was
      380days (range: 150days-2.5 years), and cut of was observed in 9 patients
      (10.5%). The following variables identified through univariate analysis with
      p<0.2 were included in multivariant logistic regression model: age, side,
      reduction quality, implant length, TAD and ASA score. Only TAD (p=0.003) was
      found to be significant in the multivariant model. CONCLUSIONS: Our study
      confirmed that risk factors for cut-out with single-lag screw devices are also
      applicable to dual-lag screw implants. We found that TAD was a significant factor
      for cut-out in dual-lag screw implants. Thus, screw cut-out can be minimized by
      optimizing screw position.

PMID- 27889114
TI  - The hidden web and the fentanyl problem: Detection of ocfentanil as an adulterant
      in heroin.
AB  - BACKGROUND: The popularization of anonymous markets such as Silk Road is
      challenging current drug policy and may provide a new context for old issues,
      such as adulteration of heroin with fentanyl derivatives. The aims of this paper
      are to report the presence of ocfentanil, a novel, potent, non-controlled
      fentanyl analog, in samples sold as heroin in the hidden web, and to summarize
      the effects reported by users. METHODS: In 2015, four samples allegedly bought as
      heroin in cryptomarkets of the hidden web were sent to Energy Control for
      analysis. Energy Control is a Spanish harm reduction NGO that offers anonymous
      drug checking with the purpose of adapting counselling to the specific substances
      present in the drug and monitor the drug market. Identification was performed by
      GC/MS and LC/MS/MS. We contacted the submitters of the samples and performed an
      Internet search to retrieve additional information. RESULTS: One sample contained
      ocfentanil, caffeine and heroin. Three samples contained the aforementioned
      substances plus paracetamol. Two out of the four contacted users reported
      distinct short acting, opioid-like effects. No fora discussion could be found
      about the effects of ocfentanil, neither web pages nor individuals advertising
      the substance. CONCLUSION: We report the presence of a new substance detected in
      the hidden web as an adulterant of heroin, ocfentanil. It has short acting opioid
      like effects, roughly the same potency as fentanyl, and can be injected, snorted
      or smoked. Severe side effects have been associated with its use, including one
      death. No discussion about this substance could be found in the Internet, which
      suggests this substance has not been sold as such. Available data about purities
      of drugs purchased in cryptomarkets suggest that adulteration is not a severe
      problem and this agrees with users' perceptions. However, this study suggests
      that adulteration is a real threat not only at the street level, but also for
      users that buy substances in cryptomarkets, and suggest the need for harm
      reduction initiatives in this setting.

PMID- 27889115
TI  - New psychoactive substances: Are there any good options for regulating new
      psychoactive substances?
AB  - Advances in chemistry, technology, and globalization have contributed to the
      rapid development and diffusion of NPS (new psychoactive substances), creating
      perhaps the most serious challenge to the century-old international drug control
      system and to national systems. Very little is known about the effects of these
      substances which fall outside of national and international controls. The
      predominant response to the flood of NPS has been the development of more
      expeditious methods of prohibiting a new chemical entity. This article explores
      alternative mechanisms that have been considered: foodstuffs, alcohol and tobacco
      and medicines. None seems promising in terms of avoiding the problems of
      prohibition without permitting unsafe substances on the market. The article then
      considers whether there is a bias in the existing system toward excessive
      prohibition. In public discussion, no attention is given to the pleasures that
      users obtain from any NPS, to the possibility of substitution for a more
      dangerous legal or illegal drug or to the consequences of illegal markets for
      prohibited NPS. On the other hand, it may well be impossible to obtain meaningful
      assessments on any of these matters at the time when decisions are made. These
      complexities have led a number of countries, most recently Australia and the UK,
      to impose total bans, the effects of which are impossible to predict.

PMID- 27889116
TI  - Total phallic reconstruction using radial forearm free flap after iatrogenic
      penile amputation.
AB  - INTRODUCTION: The iatrogenic loss of the penis is a rare situation. We present a
      challenging case of deferred total penile reconstruction in a genetic male.
      MATERIAL AND METHODS: A 57-year-old man with the loss of the penis due to a
      penile abscess and necrosis secondary to penile curvature surgery. The
      reconstruction was performed over several operations using a radial forearm free
      flap (RFFF) and placement of a customised inflatable prosthesis a year later.
      RESULTS: During the first operation, the penile abscess was drained, the necrotic
      residues were debrided and placement of hypogastric drainage. Seven weeks later,
      phalloplasty was performed with RFFF and a tube-in-tube neourethra was
      constructed. Multiple microsurgical anastomosis was performed, and the donor site
      was coated with a skin graft from the thigh of partial thickness. The surgery
      lasted 10hours and had the complication of hair growth in the neourethra, which
      required mechanical endoscopic depilation on repeated occasions. The patient
      regained penile sensitivity. Eighteen months after the phalloplasty, a Zephyr
      single-body inflatable prosthesis (Geneva, Switzerland) was implanted, using the
      tunica albuginea of the proximal corpus cavernosum. The patient was satisfied
      with the aesthetics and urinary and sensory function. Four months later, the
      patient is gaining confidence to consider penetration. CONCLUSIONS: Despite the
      risk of postoperative complications and the need for multiple operations, phallic
      reconstruction with RFFF and the placement of a customised prosthetic implant can
      improve urinary and sexual function secondary to the loss of the penis.

PMID- 27889118
TI  - Editorial overview: Genetics of human origin: New horizons in human population
      genetics.

PMID- 27889117
TI  - Inadequate pain relief among patients with primary knee osteoarthritis.
AB  - BACKGROUND: Despite the widespread treatments for Osteoarthritis (OA), data on
      treatment patterns, adequacy of pain relief, and quality of life are limited. The
      prospective multinational Survey of Osteoarthritis Real World Therapies (SORT)
      was designed to investigate these aspects. OBJECTIVES: To analyze the
      characteristics and the patient reported outcomes of the Portuguese dataset of
      SORT at the start of observation. METHODS: Patients >= 50 years with primary knee
      OA who were receiving oral or topical analgesics were eligible. Patients were
      enrolled from seven healthcare centers in Portugal between January and December
      2011. Pain and function were evaluated using the Brief Pain Inventory (BPI) and
      WOMAC. Quality of life was assessed using the 12-Item Short Form Health Survey
      (SF-12). Inadequate Pain Relief (IPR) was defined as a score>4/10 on item 5 of
      the BPI. RESULTS: Overall, 197 patients were analyzed. The median age was 67.0
      years and 78.2% were female. Mean duration of knee OA was 6.2 years. IPR was
      reported by 51.3% of patients. Female gender (adjusted odds ratio - OR 2.15
      [95%CI 1.1, 4.5]), diabetes (OR 3.1 [95%CI 1.3, 7.7]) and depression (OR 2.24
      [95%CI 1.2, 4.3]) were associated with higher risk of IPR. Patients with IPR
      reported worst outcomes in all dimensions of WOMAC (p<0.001) and in all eight
      domains and summary components of SF-12 (p<0.001). CONCLUSIONS: Our findings
      indicate that improvements are needed in the management of pain in knee OA in
      order to achieve better outcomes in terms of pain relief, function and quality of
      life.

PMID- 27889119
TI  - Determining suitable dimensions for dairy goat feeding places by evaluating body
      posture and feeding reach.
AB  - Confined goats spend a substantial part of the day feeding. A poorly designed
      feeding place increases the risk of feeding in nonphysiological body postures,
      and even injury. Scientifically validated information on suitable dimensions of
      feeding places for loose-housed goats is almost absent from the literature. The
      aim of the present study was, therefore, to determine feeding place dimensions
      that would allow goats to feed in a species-appropriate, relaxed body posture. A
      total of 27 goats with a height at the withers of 62 to 80 cm were included in
      the study. Goats were tested individually in an experimental feeding stall that
      allowed the height difference between the feed table, the standing area of the
      forelegs, and a feeding area step (difference in height between forelegs and hind
      legs) to be varied. The goats accessed the feed table via a palisade feeding
      barrier. The feed table was equipped with recesses at varying distances to the
      feeding barrier (5-55 cm in 5-cm steps) at angles of 30 degrees , 60 degrees , 90
      degrees , 120 degrees , or 150 degrees  (feeding angle), which were filled with
      the goats' preferred food. In 18 trials, balanced for order across animals, each
      animal underwent all possible combinations of feeding area step (3 levels: 0, 10,
      and 20 cm) and of difference in height between feed table and standing area of
      forelegs (6 levels: 0, 5, 10, 15, 20, and 25 cm). The minimum and maximum reach
      at which the animals could reach feed on the table with a relaxed body posture
      was determined for each combination. Statistical analysis was performed using
      mixed-effects models. The animals were able to feed with a relaxed posture when
      the feed table was at least 10 cm higher than the standing height of the goats'
      forelegs. Larger goats achieved smaller minimum reaches and minimum reach
      increased if the goats' head and neck were angled. Maximum reach increased with
      increasing height at withers and height of the feed table. The presence of a
      feeding area step had no influence on minimum and maximum reach. Based on these
      results, the goats' feeding place can be designed to ensure that the animals are
      able to reach all of the feed in the manger or on the feed table with a relaxed
      posture, thus avoiding injuries and nonphysiological stress on joints and hooves.
      A feeding area step up to a maximum of 20 cm need not be taken into account in
      terms of feeding reach. However, the feed table must be raised at least 10 cm
      above the standing area to allow the goats to feed in a species-appropriate,
      relaxed posture.

PMID- 27889120
TI  - Comparison of commercial DNA extraction kits and quantitative PCR systems for
      better sensitivity in detecting the causative agent of paratuberculosis in dairy
      cow fecal samples.
AB  - Mycobacterium avium ssp. paratuberculosis (MAP) causes ruminant paratuberculosis
      (Johne's disease) worldwide. Oral-fecal contamination is the most important mode
      of transmission of paratuberculosis, so eradicating MAP-shedding animals could
      prevent disease propagation. Fecal culture, a well-known method for MAP
      diagnosis, requires costly specialized media and a long incubation time that
      sometimes ends in disappointing bacterial contamination. To facilitate the
      efforts of control programs, we evaluated the performance of direct fecal
      quantitative PCR (qPCR) assays for their sensitivity and robustness for MAP
      detection. Commercial kits use different strategies for extracting DNA, combined
      with qPCR systems, to detect the presence of MAP in fecal samples. In this study,
      we compared the sensitivity of 3 commercially available DNA extraction kits (A,
      B, and C) combined with 2 qPCR systems (T and V) for the detection of MAP in
      infectious cows. A total of 49 dairy cows from 5 herds were sampled twice a year
      for 3 yr and diagnosed using fecal culture and ELISA. Eight replicates of their
      fecal samples from the first sampling were tested using each DNA extraction
      method and qPCR detection system. Although all 3 of the commercial DNA extraction
      kits have been previously described as very efficient for the diagnosis of
      paratuberculosis, kit B provided the highest sensitivity. Indeed, 89% of the cows
      declared positive for paratuberculosis by both fecal culture and ELISA were
      identified with kit B, whereas only 23 and 43% of the cows were identified with
      kits A and C, respectively. Interestingly, kit B was able to detect some low-MAP
      shedders. The qPCR detection system also played a critical role: system T yielded
      qPCR with the highest sensitivity. The results of this study suggest that DNA
      extraction kit B combined with detection system T provides the best amplification
      of MAP DNA from fecal samples with the highest sensitivity and specificity.
      Although 1 DNA extraction and qPCR analysis should be adequate to confirm that an
      animal with diarrhea or other signs of paratuberculosis is positive, detecting
      low shedders at the highest sensitivity should include repetitive testing. This
      study demonstrates the importance of repetitions using the most appropriate
      method for extracting DNA from fecal samples, combined with a compatible qPCR
      system for identifying MAP-shedding animals.

PMID- 27889121
TI  - Increasing estrus expression in the lactating dairy cow.
AB  - Using an activity monitoring system (AMS) equipped with an accelerometer, 2
      experiments were conducted to test the hypotheses that (1) enhancing progesterone
      before inducing luteolysis or (2) exposing cows to estradiol cypionate (ECP) or
      testosterone propionate (TP) after luteolysis would increase occurrence and
      intensity of estrus. Our goal was to determine if more cows could be detected in
      estrus by an AMS compared with other estrus-detection aids. In experiment 1, cows
      (n=154) were fitted with both an AMS collar and a pressure-sensitive, rump
      mounted device (HeatWatch; HW) and assigned to 3 treatments: (1) no CL +
      progesterone insert (CIDR) for 5d, (2) CL only, or (3) CL + 2 CIDR inserts for 5d
      to achieve a range in concentrations of progesterone. Prostaglandin F2alpha was
      administered to all cows upon CIDR insert removal or its equivalent. Progesterone
      concentration up to 72h posttreatment was greatest in CL + 2 CIDR, followed by CL
      only, and no CL + CIDR cows. Estrus occurred 14 to 28h earlier in no CL + CIDR
      compared with CL-bearing cows. Estrus intensity was greater for CL + 2 CIDR than
      for CL-only cows. The AMS and HW detected 70 and 59% of cows defined to be in
      estrus, respectively. In experiment 2, cows (n=203) were equipped with both an
      AMS and a friction-activated, rump-mounted patch (Estrotect patch) and assigned
      to receive 1mg of ECP, 2mg of TP, or control 24h after PGF2alpha. Concentrations
      of estradiol 24 and 48h after treatment were greater in ECP cows compared with
      controls. Estrus expression detected by AMS or patches in cows defined to be in
      estrus tended to be greater or was greater for ECP compared with controls,
      respectively. Compared with controls and in response to TP or ECP, estrus
      occurred 8 to 18h earlier and was of greater intensity for ECP cows,
      respectively. The AMS and patches determined 73 and 76% of cows defined to be in
      estrus, respectively. Of cows exposed to the AMS, HW, or patches, 70, 61, and
      75%, respectively, were detected in estrus and more than 93% of these
      subsequently ovulated. In contrast, of the residual cows not detected in estrus,
      62 to 77% ovulated in the absence of detected estrus. Only ECP was successful in
      inducing more expression and intensity of estrus, and proportions of cows
      detected in estrus exceeded 80%. Given the large proportion of cows equipped with
      AMS collars ovulating in the absence of estrus, further research is warranted to
      determine if more pregnancies can be achieved by inseminating those cows not
      detected in estrus at an appropriate time when PGF2alpha is administered to
      induce luteolysis.

PMID- 27889123
TI  - Validation of the M-stage scoring system for digital dermatitis on dairy cows in
      the milking parlor.
AB  - A high prevalence of digital dermatitis (DD) and the benefits of early topical
      treatment highlight the need for simple tools for routine DD detection. The
      objective of this study was to determine the accuracy of scoring DD lesions using
      the 5 M-stage scoring system in the milking parlor compared with the trimming
      chute as the gold standard. Three observers inspected 3,585 cows and 6,991 hind
      feet from 9 farms in the milking parlor using a mirror (glued to a plastic
      kitchen spatula) and a headlamp, followed by inspection in a trimming chute
      within 5 d. Interobserver agreement for scoring DD in various settings was >=82%
      (kappa >0.74; weighted kappa >0.76). At trimming chute inspections, 68% of cows
      had at least 1 DD lesion, 19% had 1 hind leg affected, and 49% had both hind legs
      affected. Within-herd DD prevalence ranged from 16 to 81% of cows affected. True
      within-herd prevalence was 2, 6, 0, 36, and 14% for M1, M2, M3, M4, and M4.1
      lesions, respectively. At the foot level, DD prevalence was the same (58%) in the
      milking parlor and trimming chute inspection, but distribution of M-stages
      differed. Milking parlor inspection as a means of identifying the presence of DD
      lesions had a sensitivity of 92% and specificity of 88%, with positive and
      negative predictive values of 91 and 89%, respectively. Agreement between milking
      parlor and trimming chute inspections was 73% (kappa = 0.59, weighted kappa =
      0.65) for the 5 M-stage scoring system and 90% (kappa = 0.80) if only the
      presence of a lesion was noted. Test characteristics varied greatly among M
      stages, with the highest sensitivity for detecting M4 (82%) and M2 (62%) lesions,
      and the lowest for detecting M4.1 (20%), M1 (7%), and M3 (0%) lesions. In the
      milking parlor, 20% of M2 lesions were misclassified as M4.1, 8% of M4 lesions
      were misclassified as M0, and 68% of M4.1 lesions were misclassified as M4. The
      majority (87%) of DD lesions were located between the heel bulbs; 10 and 2% of DD
      lesions affected the interdigital space and the front of the foot, respectively.
      The sensitivity to detect the presence of a lesion when it occurred between the
      heel bulbs was 93%, but <67% if it occurred elsewhere on the foot. We concluded
      that inspection of the rear feet in the milking parlor was an inexpensive and
      simple method of detecting and scoring DD lesions. If the objective is to
      determine herd-level DD prevalence and routine monitoring, this method was
      adequately reliable. However, if the objective is to follow up DD in cows with
      history of interdigital hyperplasia or to detect M1 or M4.1 lesions, this method
      was not sufficiently reliable. Although DD scoring in the milking parlor as a
      routine practice should facilitate early detection, prompt treatment
      interventions, and herd monitoring, it was not sufficiently reliable to replace
      definitive identification of M-stages in the trimming chute.

PMID- 27889122
TI  - Genome-wide association study for cheese yield and curd nutrient recovery in
      dairy cows.
AB  - Cheese production and consumption are increasing in many countries worldwide. As
      a result, interest has increased in strategies for genetic selection of
      individuals for technological traits of milk related to cheese yield (CY) in
      dairy cattle breeding. However, little is known about the genetic background of a
      cow's ability to produce cheese. Recently, a relatively large panel (1,264 cows)
      of different measures of individual cow CY and milk nutrient and energy
      recoveries in the cheese (REC) became available. Genetic analyses showed
      considerable variation for CY and for aptitude to retain high proportions of fat,
      protein, and water in the coagulum. For the dairy industry, these characteristics
      are of major economic importance. Nevertheless, use of this knowledge in dairy
      breeding is hampered by high costs, intense labor requirement, and lack of
      appropriate technology. However, in the era of genomics, new possibilities are
      available for animal breeding and genetic improvement. For example,
      identification of genomic regions involved in cow CY might provide potential for
      marker-assisted selection. The objective of this study was to perform genome-wide
      association studies on different CY and REC measures. Milk and DNA samples from
      1,152 Italian Brown Swiss cows were used. Three CY traits expressing the weight
      (wt) of fresh curd (%CYCURD), curd solids (%CYSOLIDS), and curd moisture
      (%CYWATER) as a percentage of weight of milk processed, and 4 REC (RECFAT,
      RECPROTEIN, RECSOLIDS, and RECENERGY, calculated as the % ratio between the
      nutrient in curd and the corresponding nutrient in processed milk) were analyzed.
      Animals were genotyped with the Illumina BovineSNP50 Bead Chip v.2. Single marker
      regressions were fitted using the GenABEL R package (genome-wide association
      using mixed model and regression-genomic control). In total, 103 significant
      associations (88 single nucleotide polymorphisms) were identified in 10
      chromosomes (2, 6, 9, 11, 12, 14, 18, 19, 27, 28). For RECFAT and RECPROTEIN,
      high significance peaks were identified in Bos taurus autosome (BTA) 6 and BTA11,
      respectively. Marker ARS-BFGL-NGS-104610 (~104.3 Mbp) was highly associated with
      RECPROTEIN and Hapmap52348-rs29024684 (~87.4 Mbp), closely located to the casein
      genes on BTA6, with RECFAT. Genomic regions identified may enhance marker
      assisted selection in bovine cheese breeding beyond the use of protein (casein)
      and fat contents, whereas new knowledge will help to unravel the genomic
      background of a cow's ability for cheese production.

PMID- 27889124
TI  - Assessing genomic prediction accuracy for Holstein sires using bootstrap
      aggregation sampling and leave-one-out cross validation.
AB  - Since the introduction of genome-enabled prediction for dairy cattle in 2009,
      genomic selection has markedly changed many aspects of the dairy genetics
      industry and enhanced the rate of response to selection for most economically
      important traits. Young dairy bulls are genotyped to obtain their genomic
      predicted transmitting ability (GPTA) and reliability (REL) values. These GPTA
      are a main factor in most purchasing, marketing, and culling decisions until
      bulls reach 5 yr of age and their milk-recorded offspring become available. At
      that time, daughter yield deviations (DYD) can be compared with the GPTA computed
      several years earlier. For most bulls, the DYD align well with the initial
      predictions. However, for some bulls, the difference between DYD and
      corresponding GPTA is quite large, and published REL are of limited value in
      identifying such bulls. A method of bootstrap aggregation sampling (bagging)
      using genomic BLUP (GBLUP) was applied to predict the GPTA of 2,963, 2,963, and
      2,803 young Holstein bulls for protein yield, somatic cell score, and daughter
      pregnancy rate (DPR), respectively. For each trait, 50 bootstrap samples from a
      reference population comprising 2011 DYD of 8,610, 8,405, and 7,945 older
      Holstein bulls were used. Leave-one-out cross validation was also performed to
      assess prediction accuracy when removing specific bulls from the reference
      population. The main objectives of this study were (1) to assess the extent to
      which current REL values and alternative measures of variability, such as the
      bootstrap standard deviation (SD) of predictions, could detect bulls whose
      daughter performance deviates significantly from early genomic predictions, and
      (2) to identify factors associated with the reference population that inform
      about inaccurate genomic predictions. The SD of bootstrap predictions was a
      mildly useful metric for identifying bulls whose future daughter performance may
      deviate significantly from early GPTA for protein and DPR. Leave-one-out cross
      validation allowed us to identify groups of reference population bulls that were
      influential on other reference population bulls for protein yield and observe
      their effects on predictions of testing set bulls, as a whole and individually.

PMID- 27889125
TI  - Analysis of pasture supplementation strategies by means of a mechanistic model of
      ruminal digestion and metabolism in the dairy cow.
AB  - Effective pasture supplementation is critical to the efficiency of resource
      management in milk production. We understand a great deal about ruminal and
      metabolic processes in dairy cattle that control efficiency but we need to
      improve our ability to predict effects of practical feeding strategies based on
      the basic biological processes of the cow. Therefore, a large-scale pasture
      supplementation study was used to explore the details of both practical
      management and the underlying biological principles and processes involved. This
      included a multiple lactation study coupled with shorter-term experiments that
      tested the type and rate of supplementation. Basal supplementation strategies
      were (1) pasture allowance [14 kg of dry matter (DM)/d per cow] supplemented with
      milled barley grain fed twice daily in the milking parlor and pasture silage
      provided in the paddock; the ratio of grain:forage fed as supplement was
      0.75:0.25 (control; DM basis); (2) the same pasture allowance plus the same
      amounts of milled barley grain and pasture silage, but the supplements were mixed
      and chopped before being fed immediately after each milking; and (3) the same
      pasture allowance and offered a partial mixed ration comprising barley (25%) and
      corn grain (30% of DM), corn silage (20% of DM), and alfalfa hay (25% of DM)
      after each milking. In late lactation (227 d in milk), a short-term experiment
      was done feeding the same pasture allowances but with the 3 supplements offered
      at 6, 8, 10, and 12 kg of DM/d for an 11-d measurement period following
      adaptation to the diet to each of the 3 long-term supplementation groups.
      Production responses were recorded and ruminal volatile fatty acids (VFA) and pH
      were measured in a subset of animals. Model descriptions of yields of milk and
      milk constituents as well as mean concentrations of ruminal fluid VFA and ruminal
      fluid pH were compared with measured values resulting when dairy cows were fed 12
      different pasture-based diets with different levels and types of dietary
      supplement. Inputs into the model were measured dry matter intake and feed
      composition on the 12 combined treatments as well as initial body weight and
      composition. The model described milk and milk component production within 1
      standard deviation of the treatment means (less than 5% of the mean as measured
      in the root mean square error). The simulated proportions of ruminal acetate,
      propionate, and butyrate were consistent with observed effects of supplemental
      treatments and rate of supplementation; however, the error analysis showed room
      for improvement. The model described, to a general extent, the changes in ruminal
      pH; however, this investigation showed that the equations that describe ruminal
      pH need to be improved or modified. These results show that the fundamental
      knowledge of ruminal and organ metabolism in this mechanistic model is sufficient
      to describe the qualitative responses to complicated dietary strategies, but our
      quantitative understanding of the parameters involved such as degradation and
      absorption kinetics and ruminal pH still demands more specific research.

PMID- 27889126
TI  - Identification of the major yeasts isolated from high moisture corn and corn
      silages in the United States using genetic and biochemical methods.
AB  - The objective of this study was to identify species of yeasts in samples of high
      moisture corn (HMC) and corn silage (CS) collected from farms throughout the
      United States. Samples were plated and colonies were isolated for identification
      using DNA analysis. Randomly selected colonies were also identified by fatty acid
      methyl esters (FAME) and by physiological substrate profiling (ID 32C). For CS,
      Candida ethanolica, Saccharomyces bulderi, Pichia anomala, Kazachstania unispora,
      and Saccharomyces cerevisiae were the predominant yeasts. Pichia anomala,
      Issatchenkia orientalis, S. cerevisiae, and Pichia fermentans were the prevalent
      species in HMC. The 3 identification methods were in agreement at the species
      level for 16.6% of the isolates and showed no agreement for 25.7%. Agreement in
      species identification between ID 32C and DNA analysis, FAME and ID 32C, and FAME
      and DNA analysis was 41.1, 14.4, and 2.2%, respectively. Pichia anomala and I.
      orientalis were able to grow on lactic acid, whereas S. cerevisiae metabolized
      sugars (galactose, sucrose, and glucose) but failed to use lactic acid. The yeast
      diversity in CS and HMC varied due to type of feed and location. Differences in
      species assignments were seen among methods, but identification using substrate
      profiling generally corresponded with that based on DNA analysis. These findings
      provide information about the species that may be expected in silages, and this
      knowledge may lead to interventions that control unwanted yeasts.

PMID- 27889127
TI  - A comparison of semen diluents on the in vitro and in vivo fertility of liquid
      bull semen.
AB  - The aim of this study was to assess the effect of semen diluent on calving rate
      (CR) following artificial insemination with liquid bull semen stored for up to 3
      d postcollection. In experiment 1, the effect of storing liquid semen maintained
      at a constant ambient temperature in 1 of 7 different diluents [Caprogen
      (homemade), OptiXcell, BioXcell, BullXcell, INRA96, NutriXcell, or AndroMed (all
      commercially available)] on total and progressive motility was assessed on d 0,
      1, 2, and 3 postcollection. In experiment 2, the field fertility of liquid semen
      diluted in Caprogen, BioXcell, or INRA96 and inseminated on d 1, 2, or 3
      postcollection was assessed in comparison to frozen-thawed semen (total of n =
      19,126 inseminations). In experiment 3, the effect of storage temperature
      fluctuations (4 and 18 degrees C) on total and progressive motility following
      dilution in Caprogen, BioXcell, and INRA96 was assessed on d 0, 1, 2, and 3
      postcollection. In experiment 1, semen stored in Caprogen, BioXcell, and INRA96
      resulted in the highest total and progressive motility on d 1, 2, and 3 of
      storage compared with OptiXcell, BullXcell, NutriXcell, and AndroMed. In
      experiment 2, an effect of diluent on CR was found as semen diluted in BioXcell
      had a lower CR on d 1, 2, and 3 of storage (46.3, 35.4, and 34.0%, respectively)
      in comparison with Caprogen (55.8, 52.0, and 51.9%, respectively), INRA96 (55.0,
      55.1, and 52.2%, respectively), and frozen-thawed semen (59.7%). Effects were
      found of parity, cow fertility sub-index, as well as the number of days in milk
      on CR. In experiment 3, when the storage temperature of diluted semen fluctuated
      between 4 and 18 degrees C, to mimic what occurs in the field (nighttime vs.
      daytime), BioXcell had the lowest total and progressive motility in comparison to
      Caprogen and INRA96. In conclusion, diluent significantly affected sperm motility
      when stored for up to 3 d. Semen diluted in INRA96 resulted in a similar CR to
      semen diluted in Caprogen and to frozen-thawed semen, whereas that diluted in
      BioXcell resulted in a decreased CR. Consistent with this finding, semen diluted
      in BioXcell was less tolerant of temperature fluctuations than that stored in
      Caprogen or INRA96. Given that it can be used directly off the shelf, INRA96 may
      be a suitable alternative to Caprogen for the storage of liquid bull semen.

PMID- 27889128
TI  - Genome-wide association study for lactation persistency, female fertility,
      longevity, and lifetime profit index traits in Holstein dairy cattle.
AB  - Female fertility in Holstein cattle can decline when intense genetic selection is
      placed on milk production. One approach to improving fertility is to identify the
      genomic regions and variants affecting fertility traits and then incorporate this
      knowledge into selection decisions. The objectives of this study were to identify
      or refine the positions of the genomic regions associated with lactation
      persistency, female fertility traits (age at first service, cow first service to
      conception, heifer and cow nonreturn rates), longevity traits (herd life,
      indirect herd life, and direct herd life), and lifetime profit index in the North
      American Holstein dairy cattle population. A genome-wide association study was
      performed for each trait, using a single SNP (single nucleotide polymorphism)
      regression mixed linear model and imputed high-density panel (777k) genotypes. No
      associations were identified for fertility traits. Several peak regions were
      detected for lifetime profit index, lactation persistency, and longevity. The
      results overlap with previous findings and identify some novel regions for
      lactation persistency. Previously proposed causative and candidate genes
      supported by this work include DGAT1, GRINA, and CPSF1, whereas new candidate
      genes are SLC2A4RG and THRB. Thus, the chromosomal regions identified in this
      study not only confirm several previous findings but also highlight new regions
      that may contribute to genetic variation in lactation persistency and longevity
      associated traits in dairy cattle.

PMID- 27889129
TI  - Biofouling of ultrafiltration membrane by dairy fluids: Characterization of
      pioneer colonizer bacteria using a DNA metabarcoding approach.
AB  - Biofouling of filtration membranes is a major quality and performance issue for
      the dairy industry. Because biofilms that survive cleaning cycles become
      resistant over time, prevention strategies limiting the adhesion of bacteria to
      membranes should be prioritized for sustainable control of biofouling. However,
      this cannot be achieved because the pioneer bacteria colonizing these membranes
      are still unknown. Consequently, the objective of this study was to characterize
      pioneer bacteria on the filtration membrane surface and to measure the effect of
      filtration operational parameters on their diversity. Thus, milk and cheese whey
      were filtered for 5 h in concentration mode at 10 and 40 degrees C using a
      laboratory-scale crossflow filtration system equipped with flat-sheet
      ultrafiltration membranes. Pioneer colonizer bacteria found on membranes after a
      chlorinated alkaline cleaning cycle were identified using a metabarcoding
      approach targeting the 16S ribosomal RNA genes. Our results suggested that
      prevention strategies targeting biofouling should consider the nature of the
      filtered fluid and the feed temperature (36.15 and 5.09% of the variances
      observed on membranes, respectively), as well as the microbial environment of the
      dairy processing plant. In the future, it is hypothesized that cleaning
      prevention strategies will be specific to each dairy processor and their
      operational parameters.

PMID- 27889130
TI  - Can the non-pre-whitening model observer, including aspects of the human visual
      system, predict human observer performance in mammography?
AB  - PURPOSE: In mammography, images are processed prior to display. Current
      methodologies based on physical image quality measurements are however not
      designed for the evaluation of processed images. Model observers (MO) might be
      suitable for this evaluation. The aim of this study was to investigate whether
      the non-pre-whitening (NPW) MO can be used to predict human observer performance
      in mammography-like images by including different aspects of the human visual
      system (HVS). METHODS: The correlation between human and NPW MO performance has
      been investigated for the detection of disk shaped objects in simulated white
      noise (WN) and clustered lumpy backgrounds (CLB), representing quantum noise
      limited and mammography-like images respectively. The images were scored by the
      MO and five human observers in a 2-alternative forced choice experiment. RESULTS:
      For WN images it was found that the log likelihood ratio (RLR2), which expresses
      the goodness of fit, was highest (0.44) for the NPW MO without addition of HVS
      aspects. For CLB the RLR2 improved from 0.46 to 0.65 with addition of HVS
      aspects. The correlation was affected by object size and background. CONCLUSIONS:
      This study shows that by including aspects of the HVS, the performance of the NPW
      MO can be improved to better predict human observer performance. This
      demonstrates that the NPW MO has potential for image quality assessment. However,
      due to the dependencies found in the correlation, the NPW MO can only be used for
      image quality assessment for a limited range of object sizes and background
      variability.

PMID- 27889131
TI  - Development of Monte Carlo based real-time treatment planning system with fast
      calculation algorithm for boron neutron capture therapy.
AB  - PURPOSE: We simulated the effect of patient displacement on organ doses in boron
      neutron capture therapy (BNCT). In addition, we developed a faster calculation
      algorithm (NCT high-speed) to simulate irradiation more efficiently. METHODS: We
      simulated dose evaluation for the standard irradiation position (reference
      position) using a head phantom. Cases were assumed where the patient body is
      shifted in lateral directions compared to the reference position, as well as in
      the direction away from the irradiation aperture. For three groups of neutron
      (thermal, epithermal, and fast), flux distribution using NCT high-speed with a
      voxelized homogeneous phantom was calculated. The three groups of neutron fluxes
      were calculated for the same conditions with Monte Carlo code. These calculated
      results were compared. RESULTS: In the evaluations of body movements, there were
      no significant differences even with shifting up to 9mm in the lateral
      directions. However, the dose decreased by about 10% with shifts of 9mm in a
      direction away from the irradiation aperture. When comparing both calculations in
      the phantom surface up to 3cm, the maximum differences between the fluxes
      calculated by NCT high-speed with those calculated by Monte Carlo code for
      thermal neutrons and epithermal neutrons were 10% and 18%, respectively. The time
      required for NCT high-speed code was about 1/10th compared to Monte Carlo
      calculation. CONCLUSIONS: In the evaluation, the longitudinal displacement has a
      considerable effect on the organ doses. We also achieved faster calculation of
      depth distribution of thermal neutron flux using NCT high-speed calculation code.

PMID- 27889132
TI  - [Level at which control objectives are reached in patients in different
      population groups with type 2 diabetes].
AB  - INTRODUCTION: There is evidence of increased macro- and micro-vascular risk in
      diabetic patients. The objective of this study was to determine the level of
      control in patients in different population groups with type 2 diabetes. MATERIAL
      AND METHODS:  DESIGN: Descriptive cross-sectional study. LOCATION: Primary care.
      Madrid Health Service. Year: 2014. SUBJECTS: Patients over 14 years with type 2
      diabetes. Number of patientes: n=6674. MEASUREMENTS: Variables on the degree of
      control (HbA1c, systolic blood pressure [SBP], diastolic blood pressure [DBP],
      LDL-c) and variables on patient characteristics (demographic, other
      cardiovascular risk factors, complications). RESULTS: The mean age of patients
      with controlled HbA1c was 67.8 years vs. 62.9 years in the uncontrolled (P<.001).
      Patients diagnosed with hypertension have a higher percentage of control with
      respect to the undiagnosed in HbA1c, SBP, DBP and LDL-c: 51 vs. 37%, 62 vs. 43%,
      75 vs. 47% and 57 vs. 44% respectively; diagnosed with dyslipidaemia: 51 vs. 39%,
      60 vs. 49%, 70 vs. 56% and 56 vs. 46%. With a diagnosis of macroangiopathy: 46
      vs. 45%, 58 vs. 54%, 71 vs. 62% and 15 vs. 60%. All differences were
      statistically significant (P<.001). Over 50% of patients without a diagnosis of
      hypertension had an SBP> 140mmHg or DBP> 90mmHg. Over 25% of patients with
      hypertension or DL and uncontrolled levels were not receiving drug treatment.
      CONCLUSION: Control was improved in all groups, especially in younger patients,
      with particularly high cardiovascular risk by the presence of other
      cardiovascular risk factors or macroangiopathy. A significant percentage of
      patients with uncontrolled BP and cLDL were not diagnosed or receiving drug
      treatment.

PMID- 27889133
TI  - [Venous thromboembolism prevention in pregnancy and the postpartum period in
      Primary and Specialized Care].
AB  - After noting that there are a number of risk factors for venous thromboembolism
      disease during pregnancy, it emphasizes primary prevention and treatment of this
      serious condition during pregnancy and the postpartum period are essential to
      reduce maternal morbidity and mortality. Low molecular-weight heparins are under
      the anticoagulant of choice in pregnancy. Your prescription may make both the
      primary care physician, as the hematologist and obstetrician. As for prescribing
      terms, an application protocol in both primary and specialized, multidisciplinary
      care, based on the existing literature on the subject is presented, which
      indicated that the hypercoagulable disorders associated with some of the risk
      factors, forced to do thromboprophylaxis with low molecular-weight heparins
      throughout pregnancy and the postpartum period presented.

PMID- 27889134
TI  - Neural adaptive observer-based sensor and actuator fault detection in nonlinear
      systems: Application in UAV.
AB  - A new online detection strategy is developed to detect faults in sensors and
      actuators of unmanned aerial vehicle (UAV) systems. In this design, the weighting
      parameters of the Neural Network (NN) are updated by using the Extended Kalman
      Filter (EKF). Online adaptation of these weighting parameters helps to detect
      abrupt, intermittent, and incipient faults accurately. We apply the proposed
      fault detection system to a nonlinear dynamic model of the WVU YF-22 unmanned
      aircraft for its evaluation. The simulation results show that the new method has
      better performance in comparison with conventional recurrent neural network-based
      fault detection strategies.

PMID- 27889135
TI  - Novel PCR-RFLP system based on rpoB gene for differentiation of Cronobacter
      species.
AB  - Bacteria from the genus Cronobacter are opportunistic foodborne pathogens that
      can cause severe infections. More rapid, cost-effective and reliable methods are
      still required for the species identification of Cronobacter spp. In this study,
      we present a novel PCR-RFLP-based method that uses a newly designed pair of
      primers for the PCR-amplification of a partial rpoB gene sequence (1635 bp). The
      amplified products of DNA from 80 Cronobacter strains were separately digested
      with three restriction endonucleases (Csp6I, HinP1I, MboI). Using the obtained
      restriction patterns, a PCR-RFLP identification system was created to enable
      differentiation between all seven currently-known Cronobacter species. The
      functionality of our method was successfully verified on real food samples.
      Moreover, the relationships between the Cronobacter species were determined via a
      phylogenetic tree created from the RFLP patterns.

PMID- 27889136
TI  - Characterization of the microbiota in lightly salted bighead carp (Aristichthys
      nobilis) fillets stored at 4  degrees C.
AB  - The microbiota of unsalted and salted (dry-cured with 2% salt) bighead carp
      (Aristichthys nobilis) fillets during storage at 4  degrees C were identified by
      16S rRNA gene analysis. Eleven genera were present in the initial microbiota of
      bighead carp fillets, where Acinetobacter, Aeromonas and Kocuria were the
      dominant bacteria. As storage time progressed, the microbial composition of both
      unsalted and salted fillets became less diverse. Additionally, differences in
      microbiota were observed between these two treatments. For unsalted bighead carp
      fillets, Aeromonas became the dominant genus at the end of storage and
      Pseudomonas was found less commonly. For salted fillets, Pseudomonas was the only
      bacteria identified at the end of storage.

PMID- 27889137
TI  - Microbial decontamination of onion powder using microwave-powered cold plasma
      treatments.
AB  - The effects of microwave-integrated cold plasma (CP) treatments against spores of
      Bacillus cereus and Aspergillus brasiliensis and Escherichia coli O157:H7 on
      onion powder were investigated. The growth of B. cereus, A. brasiliensis, and E.
      coli O157:H7 in the treated onion powder was assessed during storage at 4 and 25 
      degrees C, along with the physicochemical and sensory properties of the powder.
      Onion powder inoculated with B. cereus was treated with CP using helium as a
      plasma-forming gas, with simultaneous exposure to low microwave density at 170 mW
      m-2 or high microwave density at 250 mW m-2. High microwave density-CP treatment
      (HMCPT) was more effective than low microwave density-CP treatment (LMCPT) in
      inhibiting B. cereus spores, but induced the changes in the volatile profile of
      powder. Increase in treatment time in HMCPT yielded greater inhibition of B.
      cereus spores. Vacuum drying led to greater inhibition of spores of B. cereus and
      A. brasiliensis than hot-air drying. HMCPT at 400 W for 40 min, determined as the
      optimum conditions for B. cereus spore inhibition, initially reduced the numbers
      of B. cereus, A. brasiliensis, and E. coli O157:H7 by 2.1 log spores/cm2, 1.6 log
      spores/cm2, and 1.9 CFU/cm2, respectively. The reduced number of B. cereus spores
      remained constant, while the number of A. brasiliensis spores in the treated
      powder increased gradually during storage at 4 and 25  degrees C and was not
      different from the number of spores in untreated samples by the end of storage at
      4  degrees C. The E. coli counts in the treated powder fell below the level of
      detection after day 21 at both temperatures. HMCPT did not affect the color,
      antioxidant activity, or quercetin concentration of the powder during storage at
      both temperatures. The microwave-integrated CPTs showed potential for nonthermal
      decontamination of onion powder.

PMID- 27889138
TI  - 405 +/- 5 nm light emitting diode illumination causes photodynamic inactivation
      of Salmonella spp. on fresh-cut papaya without deterioration.
AB  - This study evaluated the antibacterial effect of 405 +/- 5 nm light emitting
      diode (LED) illumination against four Salmonella serovars on fresh-cut papaya and
      on fruit quality at various storage temperatures. To determine the antibacterial
      mechanism of LED illumination at 0.9 kJ/cm2, oxidative damage to DNA and membrane
      lipids of Salmonella in phosphate-buffered saline solution was measured. The
      populations of Salmonella on cut fruits were significantly (P < 0.05) reduced by
      0.3-1.3 log CFU/cm2 at chilling temperatures following LED illumination for 36-48
      h (1.3-1.7 kJ/cm2). However, at room temperature, bacterial populations increased
      rapidly to 6.3-7.0 log CFU/cm2 following LED illumination for 24 h (0.9 kJ/cm2),
      which was approximately 1.0 log lower than the number of colonies on non
      illuminated fruits. Levels of bacterial DNA oxidation significantly increased,
      whereas lipid peroxidation in bacterial membrane was not observed, suggesting
      that DNA oxidation contributes to photodynamic inactivation by LED illumination.
      LED illumination did not adversely affect the physicochemical and nutritional
      qualities of cut papaya, regardless of storage temperature. These results
      indicate that a food chiller equipped with 405 +/- 5 nm LEDs can preserve fresh
      cut papayas in retail stores without deterioration, minimizing the risk of
      salmonellosis.

PMID- 27889139
TI  - Development and application of a quantitative real-time PCR assay for rapid
      detection of the multifaceted yeast Kazachstania servazzii in food.
AB  - The beneficial contributions of Kazachstania servazzii are well-established in
      various food processes. This yeast also contributes in the spoilage of finished
      packaged food due to abundant gas production. In particular, an occurrence of K.
      servazzii was recently positively correlated with the formation of severe package
      swelling of some prepared fresh pizzas. To circumscribe this concern, a
      quantitative SYBR green real-time PCR assay based on a newly designed specific
      primer pair targeting the ribosomal ITS1-5.8S-ITS2 region of K. servazzii was
      developed. The quantification was enabled using a standard curve created from
      serially diluted plasmids containing the target sequence of the K. servazzii
      strain. A validation of the assay was achieved by enumeration of K. servazzii DNA
      copies from artificially infected culture broths containing non-contaminated
      pizza substrates. The newly developed method was then tested on total DNA
      extracted from packaged fresh pizzas, in which certain lots were swollen and thus
      suspected of containing K. servazzii. This study highlights that this newly
      developed quantitative assay is not only sufficiently sensitive, specific and
      reliable to be functionally used in food control as a routine method of
      detection, but also promising in specific studies that seek to further
      characterize the dynamic of this yeast in some increasingly popular food
      processes.

PMID- 27889140
TI  - Genotyping of methicillin-resistant Staphylococcus aureus (MRSA) isolated from
      milk and dairy products in South Italy.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen emerging in
      hospitals as well as community and livestock. MRSA is a significant and costly
      public health concern because it may enter the human food chain and contaminate
      milk and dairy products causing foodborne illness. This study aimed to determine
      the occurrence and the characteristics of MRSA isolated from 3760 samples of milk
      and dairy products in a previous survey conducted in southern Italy during 2008
      2014. Overall out of 484 S. aureus strains isolated, 40 (8.3%) were MRSA and were
      characterized by spa-typing, Multi-Locus Sequence Typing, SCCmec typing,
      Staphylococcal enterotoxins (SEs) genes, Panton-Valentine Leukocidin (PVL) genes
      and ability to form biofilm. The most frequently recovered STs were ST152 (t355
      67.5%), followed by ST398 (t899, t108-25%), ST1 (t127-5%) and ST5 (t688-2.5%).
      All isolates harboured the SCCmec type V (92.5%) or IVa (25%). In one isolate
      (2.5%), ST398/t899, the SCCmec resulted not detected. Three isolates (7.5%)
      carried one or more enterotoxin encoding genes (one strain had seg, sei, sem, sen
      and seo genes; two strains had seh gene). The 50% of isolated strains harboured
      PVL-encoding genes. Molecular analysis for icaA and icaD genes showed: 72.5% icaA
      and icaD positive, 25% only icaD gene and one icaA and icaD negative. The
      detection of MRSA in food of animal origin is a potential health hazard, thus it
      is necessary monitoring of food-producing animals and improving hygiene standards
      in food practices in order to reduce the microbiological risk to minimum.

PMID- 27889141
TI  - Exploring lot-to-lot variation in spoilage bacterial communities on commercial
      modified atmosphere packaged beef.
AB  - Understanding the factors influencing meat bacterial communities is important as
      these communities are largely responsible for meat spoilage. The composition and
      structure of a bacterial community on a high-O2 modified-atmosphere packaged beef
      product were examined after packaging, on the use-by date and two days after, to
      determine whether the communities at each stage were similar to those in samples
      taken from different production lots. Furthermore, we examined whether the taxa
      associated with product spoilage were distributed across production lots. Results
      from 16S rRNA amplicon sequencing showed that while the early samples harbored
      distinct bacterial communities, after 8-12 days storage at 6  degrees C the
      communities were similar to those in samples from different lots, comprising
      mainly of common meat spoilage bacteria Carnobacterium spp., Brochothrix spp.,
      Leuconostoc spp. and Lactococcus spp. Interestingly, abundant operational
      taxonomic units associated with product spoilage were shared between the
      production lots, suggesting that the bacteria enable to spoil the product were
      constant contaminants in the production chain. A characteristic succession
      pattern and the distribution of common spoilage bacteria between lots suggest
      that both the packaging type and the initial community structure influenced the
      development of the spoilage bacterial community.

PMID- 27889142
TI  - The microbiota of marketed processed edible insects as revealed by high
      throughput sequencing.
AB  - Entomophagy has been linked to nutritional, economic, social and ecological
      benefits. However, scientific studies on the potential safety risks in eating
      edible insects need to be carried out for legislators, markets and consumers. In
      this context, the microbiota of edible insects deserves to be deeply
      investigated. The aim of this study was to elucidate the microbial species
      occurring in some processed marketed edible insects, namely powdered small
      crickets, whole dried small crickets (Acheta domesticus), whole dried locusts
      (Locusta migratoria), and whole dried mealworm larvae (Tenebrio molitor), through
      culture-dependent (classical microbiological analyses) and -independent methods
      (pyrosequencing). A great bacterial diversity and variation among insects was
      seen. Relatively low counts of total mesophilic aerobes, Enterobacteriaceae,
      lactic acid bacteria, Clostridium perfringens spores, yeasts and moulds in all of
      the studied insect batches were found. Furthermore, the presence of several gut
      associated bacteria, some of which may act as opportunistic pathogens in humans,
      were found through pyrosequencing. Food spoilage bacteria were also identified,
      as well as Spiroplasma spp. in mealworm larvae, which has been found to be
      related to neurodegenerative diseases in animals and humans. Although viable
      pathogens such as Salmonella spp. and Listeria monocytogenes were not detected,
      the presence of Listeria spp., Staphylococcus spp., Clostridium spp. and Bacillus
      spp. (with low abundance) was also found through pyrosequencing. The results of
      this study contribute to the elucidation of the microbiota associated with edible
      insects and encourage further studies aimed to evaluate the influence of rearing
      and processing conditions on that microbiota.

PMID- 27889143
TI  - Use of natural antimicrobials to improve the quality characteristics of fresh
      "Phyllo" - A dough-based wheat product - Shelf life assessment.
AB  - This study explores the effects of chitosan and natamycin on the quality of fresh
      "Phyllo" - a dough-based wheat product, by monitoring the microbiological,
      physicochemical and sensory parameters. Four different lots of phyllo samples
      stored under aerobic packaging conditions, in the absence or presence of the
      aforementioned antimicrobials, were prepared and stored at 4  degrees C.
      Microbiological data suggested that, the combination of chitosan and natamycin
      resulted in significant reductions (1-3 log cfu/g) of the microbial species
      examined (mesophilic total viable counts; TVC), yeasts/molds, psychrotrophic and
      lactic acid bacteria (LAB), Enterobacteriaceae and coliforms) by day 10. The pH
      values of treated phyllo samples were lower on final day 10, as compared to the
      untreated phyllo, and of the Hunter color parameters (L*, b* and a*) that were
      evaluated, mostly the combined treatment of chitosan and natamycin maintained the
      original lightness (L*) and color (yellowness) stability (b*) of phyllo product
      during the storage period. Sensory data, based on overall acceptability (mean
      values of appearance and odor) scores confirmed the superiority of combined
      treatment of chitosan and natamycin, resulting in almost a doubling of the shelf
      life of fresh phyllo, while retaining excellent sensorial characteristics
      (appearance and odor) even on final storage day (10).

PMID- 27889144
TI  - Exploring the microbiota of the red-brown defect in smear-ripened cheese by 454
      pyrosequencing and its prevention using different cleaning systems.
AB  - Red-brown pigmentation can occasionally form in smeared-ripened cheese such as
      Fontina during the ripening process. This reaction is due to over-development of
      the typical microbiota present on the rind. Previous studies have demonstrated
      the relationship between red-brown pigmentation and the traditional utilization
      of wooden shelves during cheese ripening. The first part of the paper focuses on
      the characterisation of yeast and bacterial microbiota: plate counts and 454
      pyrosequencing were performed in spoiled (n = 6) and non-spoiled cheeses (n = 6)
      and on the wooden shelves used during ripening. The second part shows different
      systems tested for cleaning the wooden shelves and avoiding the development of
      the red-brown defect in cheese: washing with hot water and ozone treatment.
      Actinobacteria, dominated on the wooden shelves, suggesting to be responsible for
      the red-brown pigmentation; they were also found in traces in the defected cheese
      samples. Galactomyces and Debaryomyces were the main species characterizing the
      yeast population, with Debaryomyces being the most dominant species on the
      shelves used during ripening of the red-brown defective cheese. Hot water
      treatment reduced the microbial contamination of shelves, whereas only the ozone
      treatment ensured complete elimination of both yeast and bacteria, resulting in
      the cheese rind not having the red-brown defect.

PMID- 27889145
TI  - Potential probiotic Pichia kudriavzevii strains and their ability to enhance
      folate content of traditional cereal-based African fermented food.
AB  - With the aim of selecting starter cultures with interesting probiotic potential
      and with the ability to produce folate in a food matrix, yeast strains isolated
      from fermented cereal-based African foods were investigated. A total of 93 yeast
      strains were screened for their tolerance to pH 2 and 0.3% of bile salts. Pichia
      kudriavzevii isolates gave the best results. Selected P. kudriavzevii strains
      were tested for survival to the simulated human digestion and for adhesion to
      Caco-2 cells. Moreover, presence of folate biosynthesis genes was verified and
      production of extra and intra-cellular folate determined during growth in culture
      medium. 31% of yeast strains could tolerate pH 2, while 99% bile salts. Survival
      rate after simulated digestion ranged between 11 and 45%, while adhesion rate
      between 12 and 40%. Folate production was mainly intracellular, maximum after 24
      h of growth. To be closer to traditional cereal-based fermentations, a P.
      kudriavzevii strain with good probiotic potential was co-inoculated with
      Lactobacillus fermentum strains in a pearl millet gruel. This resulted in in situ
      folate production that peaked after 4 h. The use of strains with both probiotic
      and nutritional enrichment properties may have a greater impact for the
      consumers.

PMID- 27889146
TI  - The potential of species-specific tagatose-6-phosphate (T6P) pathway in
      Lactobacillus casei group for galactose reduction in fermented dairy foods.
AB  - Residual lactose and galactose in fermented dairy foods leads to several
      industrial and health concerns. There is very little information pertaining to
      manufacture of fermented dairy foods that are low in lactose and galactose. In
      the present study, comparative genomic survey demonstrated the constant presence
      of chromosome-encoded tagatose-6-phosphate (T6P) pathway in Lactobacillus casei
      group. Lactose/galactose utilization tests and beta-galactosidase assay suggest
      that PTSGal system, PTSLac system and T6P pathway are major contributors for
      lactose/galactose catabolism in this group of organisms. In addition, it was
      found than lactose catabolism by Lb. casei group accumulated very limited
      galactose in the MRS-lactose medium and in reconstituted skim milk, whereas
      Streptococcus thermophilus and Lb. delbrueckii subsp. bulgaricus (Lb. bulgaricus)
      strains secreted high amount of galactose extracellularly. Moreover, co-culturing
      Lb. casei group with Str. thermophilus showed significant reduction in galactose
      content, while co-culturing Lb. casei group with Lb. bulgaricus showed
      significant reduction in lactose content but significant increase in galactose
      content in milk. Overall, the present study highlighted the potential of Lb.
      casei group for reducing galactose accumulation in fermented milks due to its
      species-specific T6P pathway.

PMID- 27889147
TI  - Biocontrol of ochratoxigenic moulds (Aspergillus ochraceus and Penicillium
      nordicum) by Debaryomyces hansenii and Saccharomycopsis fibuligera during speck
      production.
AB  - Speck is a meat product obtained from the deboned leg of pork that is salted,
      smoked and seasoned for four to six months. During speck seasoning, Eurotium
      rubrum and Penicillium solitum grow on the surface and collaborate with other
      moulds and tissue enzymes to produce the typical aroma. Both of these strains
      usually predominate over other moulds. However, moulds producing ochratoxins,
      such as Aspergillus ochraceus and Penicillium nordicum, can also co-grow on speck
      and produce ochratoxin A (OTA). Consequently, speck could represent a potential
      health risk for consumers. Because A. ochraceus and P. nordicum could represent a
      problem for artisanal speck production, the aim of this study was to inhibit
      these mould strains using Debaryomyces hansenii and Saccharomycopsis fibuligera.
      Six D. hansenii and six S. fibuligera strains were tested in vitro to inhibit A.
      ochraceus and P. nordicum. The D. hansenii DIAL 1 and S. fibuligera DIAL 3
      strains demonstrated the highest inhibitory activity and were selected for in
      vivo tests. The strains were co-inoculated on fresh meat cuts for speck
      production with both of the OTA-producing moulds prior to drying and seasoning.
      At the end of seasoning (six months), OTA was not detected in the speck treated
      with both yeast strains. Because the yeasts did not adversely affect the speck
      odour or flavour, the strains are proposed as starters for the inhibition of
      ochratoxigenic moulds.

PMID- 27889148
TI  - Surface attachment of active antimicrobial coatings onto conventional plastic
      based laminates and performance assessment of these materials on the storage life
      of vacuum packaged beef sub-primals.
AB  - Two antimicrobial coatings, namely Sodium octanoate and Auranta FV (a commercial
      antimicrobial composed of bioflavonoids, citric, malic, lactic, and caprylic
      acids) were used. These two antimicrobials were surface coated onto the inner
      polyethylene layer of cold plasma treated polyamide films using beef gelatin as a
      carrier and coating polymer. This packaging material was then used to vacuum pack
      beef sub-primal cuts and stored at 4  degrees C. A control was prepared using the
      non-coated commercial laminate and the same vacuum packaged sub-primal beef cuts.
      During storage, microbial and quality assessments were carried out. Sodium
      octanoate treated packages significantly (p < 0.05) reduced microbial counts for
      all bacteria tested with an increase of 7 and 14 days, respectively compared to
      control samples. No significant effect on pH was observed with any treatment. The
      results suggested that these food grade antimicrobials have the potential to be
      used in antimicrobial active packaging applications for beef products.

PMID- 27889149
TI  - Inactivation of Salmonella enterica in chicken feces on the surface of eggshells
      by simultaneous treatments with gaseous chlorine dioxide and mild wet heat.
AB  - The aim of this study was to investigate the lethal effects of simultaneous
      treatments with gaseous chlorine dioxide (ClO2) and mild wet heat (55  degrees C
      at 100% relative humidity [RH]) on Salmonella enterica in chicken feces on the
      surface of eggshells. Gaseous ClO2 production decreased significantly (P <= 0.05)
      as the RH (23, 43, 68, 85, and 100%) at 25  degrees C was increased. The
      lethality of gaseous ClO2 against S. enterica in feces on eggshells increased
      significantly (P <= 0.05) as RH increased. For example, when treated with gaseous
      ClO2 at 85 and 100% RH at 25  degrees C, S. enterica (5.9 log CFU/egg) was
      inactivated within 4 h. In contrast, at 23, 43, and 68% RH, the pathogen remained
      at 5.1, 5.0, and 2.8 log CFU/egg, respectively, after 6 h. Finally, when
      eggshells surface-contaminated with S. enterica (5.8 log CFU/egg) were treated
      with gaseous ClO2 (peak concentration of ClO2: 185.6 ppm) at 100% RH and 55 
      degrees C, inactivation occurred within 1 h. These results indicate that
      treatment of surface-contaminated shell eggs with gaseous ClO2 at elevated RH and
      temperature is effective in inactivating S. enterica. These observations will be
      useful when developing an effective sanitation program to enhance the
      microbiological safety of shell eggs.

PMID- 27889150
TI  - Antimicrobial activity of whey protein films supplemented with Lactobacillus
      sakei cell-free supernatant on fresh beef.
AB  - The aim of this work was to evaluate the antimicrobial activity of whey protein
      isolate (WPI) films supplemented with Lactobacillus sakei NRRL B-1917 cell-free
      supernatant on beef inoculated with Escherichia coli ATCC 25922 or Listeria
      monocytogenes Scott A; additionally, sensory evaluation was performed on wrapped
      beef cubes. Supernatant concentrates were obtained from Lb. sakei cultures in MRS
      broth after centrifugation, filtering, and freeze-drying. Films were prepared
      with WPI (3% w/w), alginate (0.625% w/w), rehydrated supernatant (18 mg/ml), and
      glycerol. Films were used to wrap beef cubes inoculated with ~103 CFU/g E. coli
      or L. monocytogenes. Sensory evaluation was carried out on grilled beef wrapped
      or not with the studied antimicrobial films. During refrigerated storage,
      antimicrobial films reduced 1.4 log10 CFU/g of L. monocytogenes after 120 h,
      while E. coli decreased 2.3 log10 CFU/g after 36 h. Grilled beef wrapped with
      antimicrobial film was well accepted by panelists, besides scores evidenced no
      significant differences (p > 0.05) between wrapped and unwrapped beef.

PMID- 27889152
TI  - Application of flow cytometry to wine microorganisms.
AB  - Flow cytometry (FCM) is a powerful technique allowing detection and enumeration
      of microbial populations in food and during food process. Thanks to the
      fluorescent dyes used and specific probes, FCM provides information about cell
      physiological state and allows enumeration of a microorganism in a mixed culture.
      Thus, this technique is increasingly used to quantify pathogen, spoilage
      microorganisms and microorganisms of interest. Since one decade, FCM applications
      to the wine field increase greatly to determine population and physiological
      state of microorganisms performing alcoholic and malolactic fermentations. Wine
      spoilage microorganisms were also studied. In this review we briefly describe FCM
      principles. Next, a deep revision concerning enumeration of wine microorganisms
      by FCM is presented including the fluorescent dyes used and techniques allowing a
      yeast and bacteria species specific enumeration. Then, the last chapter is
      dedicated to fluorescent dyes which are used to date in fluorescent microscopy
      but applicable in FCM. This chapter also describes other interesting "future"
      techniques which could be applied to study the wine microorganisms. Thus, this
      review seeks to highlight the main advantages of the flow cytometry applied to
      wine microbiology.

PMID- 27889151
TI  - Efficacy of post-harvest rinsing and bleach disinfection of E. coli O157:H7 on
      spinach leaf surfaces.
AB  - Attachment and detachment kinetics of Escherichia coli O157:H7 from baby spinach
      leaf epicuticle layers were investigated using a parallel plate flow chamber.
      Mass transfer rate coefficients were used to determine the impact of water
      chemistry and common bleach disinfection rinses on the removal and inactivation
      of the pathogen. Attachment mass transfer rate coefficients generally increased
      with ionic strength. Detachment mass transfer rate coefficients were nearly the
      same in KCl and AGW rinses; however, the detachment phase lasted longer in KCl
      than AGW (18 +/- 4 min and 4 +/- 2 min, respectively), indicating that the ions
      present during attachment play a significant role in the cells' ability to remain
      attached. Specifically, increasing bleach rinse concentration by two orders of
      magnitude was found to increase the detachment mass transfer rate coefficient by
      20 times (from 5.7 +/- 0.7 * 10-11 m/s to 112.1 +/- 26.8 * 10-11 m/s for 10 ppb
      and 1000 ppb, respectively), and up to 88 +/- 4% of attached cells remained
      alive. The spinach leaf texture was incorporated within a COMSOL model of
      disinfectant concentration gradients, which revealed nearly 15% of the leaf
      surface is exposed to almost 1000 times lower concentration than the bulk rinse
      solution.

PMID- 27889153
TI  - Metagenomics reveals flavour metabolic network of cereal vinegar microbiota.
AB  - Multispecies microbial community formed through centuries of repeated batch
      acetic acid fermentation (AAF) is crucial for the flavour quality of traditional
      vinegar produced from cereals. However, the metabolism to generate and/or
      formulate the essential flavours by the multispecies microbial community is
      hardly understood. Here we used metagenomic approach to clarify in situ metabolic
      network of key microbes responsible for flavour synthesis of a typical cereal
      vinegar, Zhenjiang aromatic vinegar, produced by solid-state fermentation. First,
      we identified 3 organic acids, 7 amino acids, and 20 volatiles as dominant
      vinegar metabolites. Second, we revealed taxonomic and functional composition of
      the microbiota by metagenomic shotgun sequencing. A total of 86 201 predicted
      protein-coding genes from 35 phyla (951 genera) were involved in Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathways of Metabolism (42.3%), Genetic
      Information Processing (28.3%), and Environmental Information Processing (10.1%).
      Furthermore, a metabolic network for substrate breakdown and dominant flavour
      formation in vinegar microbiota was constructed, and microbial distribution
      discrepancy in different metabolic pathways was charted. This study helps
      elucidating different metabolic roles of microbes during flavour formation in
      vinegar microbiota.

PMID- 27889154
TI  - Prevalence and quantification of thermophilic Campylobacter spp. in Italian
      retail poultry meat: Analysis of influencing factors.
AB  - Retail poultry meat is a crucial vehicle for consumers' exposure to
      Campylobacters, but no official controls are currently applied in Italy. The aim
      of this study was the evaluation of Campylobacter contamination of a wide range
      of poultry meats marketed in Italy. N. 472 chicken and turkey meat samples
      (sectioned meats, offal, meat preparations and products) were taken from
      slaughterhouses, deboning plants and different retailers and submitted to
      detection/enumeration of Campylobacter spp. The isolates were identified by
      phenotypic and biomolecular techniques. Campylobacter spp. was detected in 34.1%
      of the samples, with general low counts. Higher values were observed in offal
      (especially liver) and sectioned meats, with significantly higher rates in skin
      on samples (86.8% vs 32.7%). Minced meat preparations showed lower prevalence
      (22.4% vs 58.3%) and counts than whole pieces. Decreasing rates were observed
      among slaughterhouses (80%), deboning plants (49%), butcher's shops (37%) and
      large scale retailers (25%). Sectioned chicken meats were significantly more
      contaminated than turkey meats. Almost all the isolates were identified as C.
      jejuni or C. coli, with similar prevalences (18.4% and 20.5%, respectively); C.
      jejuni was predominant only in samples from slaughterhouses/deboning plants. For
      setting future control programs, meat typology should be considered the main
      critical factor.

PMID- 27889156
TI  - Survival of hepatitis A virus and Aichi virus in cranberry-based juices at
      refrigeration (4  degrees C).
AB  - Viral foodborne illness continues to be a health-concern globally, with numerous
      fruit and juice outbreaks of Hepatitis A virus (HAV) reported worldwide. Aichi
      virus (AiV) is an emerging pathogen with limited epidemiological data. Both, HAV
      and AiV are resistant to low pH and can survive under adverse environmental
      conditions leading to transmission ease. The objective of this study was to
      evaluate the survival of HAV and AiV in commercially-available cranberry-based
      juices (Cranberry juice cocktail, CJ and a 100% juice with cranberry, MJ) over 21
      days at refrigeration (4  degrees C). Equal volumes of juice was mixed with each
      virus individually (final titer of 6 log PFU/mL) and stored at refrigeration over
      21 days. At each time interval, the inoculated juices were serially diluted in
      cell culture media and infectious virus survival was determined by standard
      plaque assays. Each experiment was carried out in duplicate and replicated
      thrice. Reductions of 0.72 +/- 0.06 (after day 1) to 2.3 +/- 0.18 log PFU/mL
      (after day 21) and 0.63 +/- 0.02 (after day 1) to 1.84 +/- 0.14 log PFU/mL (after
      day 21) were obtained for AiV with MJ and CJ, respectively. Reductions ranging
      from 0.67 +/- 0.03 (after day 1) to 1.09 +/- 0.1 log PFU/mL (after day 21) and
      0.93 +/- 0.27 (after day1) to 1.49 +/- 0.18 log PFU/mL (after day 21) were
      obtained for HAV at refrigeration in MJ and CJ, respectively. HAV showed greater
      survival than AiV in these juices over refrigerated storage. These results
      provide survival data of HAV and AiV in cranberry-based juices that can be used
      in risk-modeling and risk assessment studies.

PMID- 27889155
TI  - Genetic basis for mycophenolic acid production and strain-dependent production
      variability in Penicillium roqueforti.
AB  - Mycophenolic acid (MPA) is a secondary metabolite produced by various Penicillium
      species including Penicillium roqueforti. The MPA biosynthetic pathway was
      recently described in Penicillium brevicompactum. In this study, an in silico
      analysis of the P. roqueforti FM164 genome sequence localized a 23.5-kb putative
      MPA gene cluster. The cluster contains seven genes putatively coding seven
      proteins (MpaA, MpaB, MpaC, MpaDE, MpaF, MpaG, MpaH) and is highly similar (i.e.
      gene synteny, sequence homology) to the P. brevicompactum cluster. To confirm the
      involvement of this gene cluster in MPA biosynthesis, gene silencing using RNA
      interference targeting mpaC, encoding a putative polyketide synthase, was
      performed in a high MPA-producing P. roqueforti strain (F43-1). In the obtained
      transformants, decreased MPA production (measured by LC-Q-TOF/MS) was correlated
      to reduced mpaC gene expression by Q-RT-PCR. In parallel, mycotoxin
      quantification on multiple P. roqueforti strains suggested strain-dependent MPA
      production. Thus, the entire MPA cluster was sequenced for P. roqueforti strains
      with contrasted MPA production and a 174bp deletion in mpaC was observed in low
      MPA-producers. PCRs directed towards the deleted region among 55 strains showed
      an excellent correlation with MPA quantification. Our results indicated the clear
      involvement of mpaC gene as well as surrounding cluster in P. roqueforti MPA
      biosynthesis.

PMID- 27889157
TI  - Monitoring of wheat lactic acid bacteria from the field until the first step of
      dough fermentation.
AB  - The present work was carried out to retrieve the origin of lactic acid bacteria
      (LAB) in sourdough. To this purpose, wheat LAB were monitored from ear harvest
      until the first step of fermentation for sourdough development. The influence of
      the geographical area and variety on LAB species/strain composition was also
      determined. The ears of four Triticum durum varieties (Duilio, Iride, Saragolla
      and Simeto) were collected from several fields located within the Palermo
      province (Sicily, Italy) and microbiologically investigated. In order to trace
      the transfer of LAB during the consecutive steps of manipulation, ears were
      transformed aseptically and, after threshing, milling and fermentation, samples
      of kernels, semolinas and doughs, respectively, were analysed. LAB were not found
      to dominate the microbial communities of the raw materials. In general, kernels
      harboured lower levels of microorganisms than ears and ears than semolinas.
      Several samples showing no development of LAB colonies acidified the enrichment
      broth suggesting the presence of LAB below the detection limit. After
      fermentation, LAB loads increased consistently for all doughs, reaching levels of
      7.0-7.5 Log CFU/g on M17. The values of pH (5.0) and TTA (5.6 mL NaOH/10 g of
      dough) indicated the occurrence of the acidification process for several doughs.
      LAB were phenotypically and genotypically differentiated by randomly amplified
      polymorphic DNA (RAPD)-PCR into eight groups including 51 strains belonging to
      the species Lactobacillus brevis, Lactobacillus coryniformis, Lactobacillus
      plantarum, Lactococcus lactis, Lactococcus garvieae, Enterococcus casseliflavus,
      Enterococcus faecium, Leuconostoc citreum, and Pediococcus pentosaceus.
      Lactobacilli constituted a minority the LAB community, while lactococci
      represented more than 50% of strains. Lower LAB complexity was found on kernels,
      while a richer biodiversity was observed in semolinas and fermented doughs. For
      broader microbiota characterisation in doughs before fermentation, the 16S rRNA
      gene fragment profiling was conducted on the unfermented doughs using MiSeq
      Illumina. LAB group was represented by Enterococcus, Lactococcus and members of
      Leuconostocaceae family whose relative abundances differed according to both
      geographical area and variety of wheat. The culture-independent approach
      confirmed that pediococci and lactobacilli constituted low abundance members of
      the semolina LAB microbiota and that although some strains may pass from wheat
      ear to fermented doughs, most are likely to come from other sources.

PMID- 27889158
TI  - Fat and fibre interfere with the dramatic effect that nanoemulsified d-limonene
      has on the heat resistance of Listeria monocytogenes.
AB  - The application of d-limonene in form of nanoemulsion has been proved to reduce
      dramatically the thermal resistance of Listeria monocytogenes in culture media.
      The present research shows very promising results on the application in food
      products. The thermal resistance of L. monocytogenes was reduced 90 times when
      0.5 mM nanoemulsified d-limonene was added to apple juice. This is the biggest
      reduction in the heat resistance of a microorganism caused by an antimicrobial
      described ever. However, no effect was found in carrot juice. A carrot juice
      system was prepared in an attempt to unravel which juice constituents were
      responsible for the lack of effect. When fat and fibre were not included in the
      carrot juice system formulation, the thermal resistance of L. monocytogenes was,
      again, dramatically reduced in presence of nanoemulsified d-limonene, so these
      components were shown to interfere with the effect. Once this interaction with
      food constituents becomes solved, the addition of nanoemulsified antimicrobials
      would allow to reduce greatly the intensity of the thermal treatments currently
      applied in the food processing industry.

PMID- 27889159
TI  - Exposure to minimally processed pear and melon during shelf life could modify the
      pathogenic potential of Listeria monocytogenes.
AB  - Survival and virulence of foodborne pathogens can be influenced by environmental
      factors such as the intrinsic properties of food as well as the extrinsic
      properties that contribute to food shelf life (e.g., temperature and gas
      atmosphere). The direct contribution of food matrix characteristics on the
      survival of L. monocytogenes during fresh-cut fruit shelf life is not very well
      understood. In addition, the gastrointestinal tract is the primary route of
      listeriosis infection and penetration of the intestinal epithelial cell barrier
      is the first step in the infection process. Hence, the pathogenic potential of L.
      monocytogenes, measured as the capability for the organism to survive a simulated
      gastrointestinal tract and the proportion of cells able to subsequently adhere to
      and invade differentiated Caco-2 cells, subjected to fresh-cut pear and melon
      shelf life, was investigated. Samples were inoculated, stored at 10  degrees C
      for 7 days and evaluated after inoculation and again after 2 and 7 days of
      storage. A decrease in L. monocytogenes' capacity to survive a simulated
      gastrointestinal tract was observed with increasing storage time, regardless of
      the fruit matrix evaluated. Furthermore, L. monocytogenes placed on fresh-cut
      pear and melon was subjected to an attachment and invasion assay after crossing
      the simulated gastrointestinal tract. After inoculation, pathogen on fresh-cut
      pear showed 5-fold more capacity to adhere to Caco-2 cells than pathogen on fresh
      cut melon. After 2 days of storage, L. monocytogenes grown on fresh-cut melon
      showed similar adhesive capacity (1.11%) than cells grown on pear (1.83%), but
      cells grown on melon had the higher invasive capacity (0.0093%). We can conclude
      that minimally processed melon could represent a more important hazard than pear
      under the studied shelf life.

PMID- 27889160
TI  - Evaluation of baker's yeast in honey using a real-time PCR assay.
AB  - Occasionally, melissopalynological analysis reveals the presence of baker's yeast
      (Saccharomyces cerevisiae) in honey sediments. A field experiment reproducing a
      common spring bee feeding practice, using sugar paste containing baker's yeast,
      was performed to understand how S. cerevisiae are introduced into honey. Apart
      from classical microscopy, a real-time quantitative PCR (qPCR) system specific
      for S. cerevisiae was established for quantification of S. cerevisiae in honeys.
      Results showed that S. cerevisiae cells are stored in the honey of the brood
      combs and are also transferred into honey in the supers. The concentrations of S.
      cerevisiae were highest in honey of the brood frames immediately after the
      feeding and decreased over time to low concentrations at the end of the year. A
      high content of S. cerevisiae cells were also found in the honey from supers of
      the spring harvest. Observed S. cerevisiae cells were not able to multiply in a
      high-sugar environment, such as honey, and their viability decreased rapidly
      after addition to the honey. The screening of 200 Swiss honeys revealed the
      presence of S. cerevisiae in 4.5% of the samples, as determined by microscopy and
      qPCR. Finally, the method described here may indicate an unwanted sucrose
      addition to honey through bee-feeding.

PMID- 27889161
TI  - MRSA and multidrug-resistant Staphylococcus aureus in U.S. retail meats, 2010
      2011.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been detected in retail
      meats, although large-scale studies are scarce. We conducted a one-year survey in
      2010-2011 within the framework of the National Antimicrobial Resistance
      Monitoring System. Among 3520 retail meats collected from eight U.S. states, 982
      (27.9%) contained S. aureus and 66 (1.9%) were positive for MRSA. Approximately
      10.4% (107/1032) of S. aureus isolates, including 37.2% (29/78) of MRSA, were
      multidrug-resistant (MDRSA). Turkey had the highest MRSA prevalence (3.5%),
      followed by pork (1.9%), beef (1.7%), and chicken (0.3%). Whole-genome sequencing
      was performed for all 66 non-redundant MRSA. Among five multilocus sequence types
      identified, ST8 (72.7%) and ST5 (22.7%) were most common and livestock-associated
      MRSA ST398 was assigned to one pork isolate. Eleven spa types were represented,
      predominately t008 (43.9%) and t2031 (22.7%). All four types of meats harbored
      t008, whereas t2031 was recovered from turkey only. The majority of MRSA (84.8%)
      possessed SCCmec IV and 62.1% harbored Panton-Valentine leukocidin. Pulsed-field
      gel electrophoresis showed that all ST8 MRSA belonged to the predominant human
      epidemic clone USA300, and others included USA100 and USA200. We conclude that a
      diverse MRSA population was present in U.S. retail meats, albeit at low
      prevalence.

PMID- 27889162
TI  - Tolerance of Clostridium perfringens biofilms to disinfectants commonly used in
      the food industry.
AB  - Clostridium perfringens is an opportunistic pathogen that can cause food
      poisoning in humans and various enterotoxemia in animal species. Recently, it was
      shown to form mono-species biofilms, a structured community of bacterial cells
      enclosed in a self-produced extracellular matrix. Biofilms have been associated
      with tolerance to antibiotics, disinfectants, and physical and environmental
      stresses. Very little is known about the tolerance of C. perfringens biofilm
      toward disinfectants. In the present study, susceptibilities of C. perfringens
      biofilms to five types of commonly used disinfectants on farms and in food
      processing environments were analysed. In this paper, we show that C. perfringens
      mono-species biofilms can protect the bacterial cells from the action of
      potassium monopersulfate, quaternary ammonium chloride, hydrogen peroxide and
      glutaraldehyde solutions. However, sodium hypochlorite solution was shown to be
      effective on C. perfringens biofilms. Our investigation of dual-species biofilms
      of C. perfringens with the addition of Staphylococcus aureus or Escherichia coli
      demonstrated that overall, the mono-species biofilm of C. perfringens was more
      tolerant to all disinfectants than the dual-species biofilms. For the anaerobic
      grown biofilms, the mono-species biofilm of C. perfringens was more tolerant to
      sodium hypochlorite and quaternary ammonium chloride than the dual-species
      biofilms of C. perfringens with S. aureus or E. coli. This study demonstrates
      that C. perfringens biofilm is an effective protection mechanism to disinfectants
      commonly used on farms and in food processing environments.

PMID- 27889163
TI  - Differential detection of pathogenic Yersinia spp. by fluorescence in situ
      hybridization.
AB  - Yersinia enterocolitica, Y. pseudotuberculosis and Y. pestis are pathogens of
      major medical importance, which are responsible for a considerable number of
      infections every year. The detection of these species still relies on cultural
      methods, which are slow, labour intensive and often hampered by the presence of
      high amounts of accompanying flora. In this study, fluorescence in situ
      hybridization (FISH) was used to develop a fast, sensitive and reliable
      alternative to detect viable bacteria in food. For this purpose, highly specific
      probes targeting the 16S and 23S ribosomal RNA were employed to differentially
      detect each of the three species. In order to enable the differentiation of
      single nucleotide polymorphisms (SNPs), suitable competitor oligonucleotides and
      locked nucleic acids (LNAs) were used. Starved cells still showed a strong signal
      and a direct viable count (DVC) approach combined with FISH optimized live/dead
      discrimination. Sensitivity of the FISH test was high and even a single cell per
      gram of spiked minced pork meat could be detected within a day, demonstrating the
      applicability to identify foodborne hazards at an early stage. In conclusion, the
      established FISH tests proved to be promising tools to compensate existing
      drawbacks of the conventional cultural detection of these important zoonotic
      agents.

PMID- 27889164
TI  - Multilocus sequence type profiles of Bacillus cereus isolates from infant formula
      in China.
AB  - Bacillus cereus sensu stricto is an opportunistic foodborne pathogen. The
      multilocus sequence type (MLST) of 74 B. cereus isolated from 513 non-random
      infant formula in China was analyzed. Of 64 sequence types (STs) detected, 50 STs
      and 6 alleles were newly found in PubMLST database. All isolates except for one
      singleton (ST-1049), were classified into 7 clonal complexes (CC) by BURST (n-4),
      in which CC1 with core ancestral clone ST-26 was the largest group including 86%
      isolates, and CC2, 3, 9, 10 and 13 were first reported in China. MLST profiles of
      the isolates from 8 infant formula brands were compared. It was found the brands
      might be potentially tracked by the variety of STs, such as ST-1049 of singleton
      and ST-1062 of isolate from goat milk source, though they could not be easily
      tracked just by clonal complex types of the isolates.

PMID- 27889165
TI  - Effect of inoculum size, bacterial species, type of surfaces and contact time to
      the transfer of foodborne pathogens from inoculated to non-inoculated beef
      fillets via food processing surfaces.
AB  - The objective of the present study was to determine the factors affecting the
      transfer of foodborne pathogens from inoculated beef fillets to non-inoculated
      ones, through food processing surfaces. Three different levels of inoculation of
      beef fillets surface were prepared: a high one of approximately 107 CFU/cm2, a
      medium one of 105 CFU/cm2 and a low one of 103 CFU/cm2, using mixed-strains of
      Listeria monocytogenes, or Salmonella enterica Typhimurium, or Escherichia coli
      O157:H7. The inoculated fillets were then placed on 3 different types of surfaces
      (stainless steel-SS, polyethylene-PE and wood-WD), for 1 or 15 min. Subsequently,
      these fillets were removed from the cutting boards and six sequential non
      inoculated fillets were placed on the same surfaces for the same period of time.
      All non-inoculated fillets were contaminated with a progressive reduction trend
      of each pathogen's population level from the inoculated fillets to the sixth non
      inoculated ones that got in contact with the surfaces, and regardless the initial
      inoculum, a reduction of approximately 2 log CFU/g between inoculated and 1st non
      inoculated fillet was observed. S. Typhimurium was transferred at lower mean
      population (2.39 log CFU/g) to contaminated fillets than E. coli O157:H7 (2.93
      log CFU/g), followed by L. monocytogenes (3.12 log CFU/g; P < 0.05). Wooden
      surfaces (2.77 log CFU/g) enhanced the transfer of bacteria to subsequent fillets
      compared to other materials (2.66 log CFU/g for SS and PE; P < 0.05). Cross
      contamination between meat and surfaces is a multifactorial process strongly
      depended on the species, initial contamination level, kind of surface, contact
      time and the number of subsequent fillet, according to analysis of variance.
      Thus, quantifying the cross-contamination risk associated with various steps of
      meat processing and food establishments or households can provide a scientific
      basis for risk management of such products.

PMID- 27889166
TI  - Taggiasca extra virgin olive oil colonization by yeasts during the extraction
      process.
AB  - The opalescent appearance of the newly produced olive oil is due to the presence
      of solid particles and microdrops of vegetation water in which the microorganisms
      from the olives' carposphere are trapped. Present research has demonstrated that
      the microbiota of the fresh extracted olive oil, produced in the mills, is mainly
      composed of yeasts and to a lesser extent of molds. The close link between the
      composition of the microbiota of the olives' carposphere undergoing to
      processing, and that of the microbiota of the newly produced olive oil, concerns
      only the yeasts and molds, given that the bacterial component is by and large
      destroyed mainly in the kneaded paste during the malaxation process. Six
      physiologically homogenous yeast groups were highlighted in the wash water,
      kneaded paste and newly produced olive oil from the Taggiasca variety which had
      been collected in mills located in the Liguria region. The more predominant
      yeasts of each group belonged to a single species called respectively:
      Kluyveromyces marxianus, Candida oleophila, Candida diddensiae, Candida
      norvegica, Wickerhamomyces anomalus and Debaryomyces hansenii. Apart from K.
      marxianus, which was found only in the wash water, all the other species were
      found in the wash water and in the kneaded paste as well as in the newly produced
      olive oil, while in the six-month stored olive oil, was found only one
      physiologically homogeneous group of yeast represented by the W. anomalus specie.
      These findings in according to our previous studies carried out on other types of
      mono varietal olive oils, confirms that the habitat of the Taggiascas' extra
      virgin olive oil, had a strong selective pressure on the yeast biota, allowing
      only to a few member of yeast species, contaminating the fresh product, to
      survive and reproduce in it during storage.

PMID- 27889167
TI  - Sonication reduces the attachment of Salmonella Typhimurium ATCC 14028 cells to
      bacterial cellulose-based plant cell wall models and cut plant material.
AB  - This study investigated the removal of bacterial surface structures, particularly
      flagella, using sonication, and examined its effect on the attachment of
      Salmonella Typhimurium ATCC 14028 cells to plant cell walls. S. Typhimurium ATCC
      14028 cells were subjected to sonication at 20 kHz to remove surface structures
      without affecting cell viability. Effective removal of flagella was determined by
      staining flagella of sonicated cells with Ryu's stain and enumerating the
      flagella remaining by direct microscopic counting. The attachment of sonicated S.
      Typhimurium cells to bacterial cellulose-based plant cell wall models and cut
      plant material (potato, apple, lettuce) was then evaluated. Varying
      concentrations of pectin and/or xyloglucan were used to produce a range of
      bacterial cellulose-based plant cell wall models. As compared to the non
      sonicated controls, sonicated S. Typhimurium cells attached in significantly
      lower numbers (between 0.5 and 1.0 log CFU/cm2) to all surfaces except to the
      bacterial cellulose-only composite without pectin and xyloglucan. Since
      attachment of S. Typhimurium to the bacterial cellulose-only composite was not
      affected by sonication, this suggests that bacterial surface structures,
      particularly flagella, could have specific interactions with pectin and
      xyloglucan. This study indicates that sonication may have potential applications
      for reducing Salmonella attachment during the processing of fresh produce.

PMID- 27889168
TI  - Biofilm formation enhances Helicobacter pylori survivability in vegetables.
AB  - To date, the exact route and mode of transmission of Helicobacter pylori remains
      elusive. The detection of H. pylori in food using molecular approaches has led us
      to postulate that the gastric pathogen may survive in the extragastric
      environment for an extended period. In this study, we show that H. pylori
      prolongs its survival by forming biofilm and micro-colonies on vegetables. The
      biofilm forming capability of H. pylori is both strain and vegetable dependent.
      H. pylori strains were classified into high and low biofilm formers based on
      their highest relative biofilm units (BU). High biofilm formers survived longer
      on vegetables compared to low biofilm formers. The bacteria survived better on
      cabbage compared to other vegetables tested. In addition, images captured on
      scanning electron and confocal laser scanning microscopes revealed that the
      bacteria were able to form biofilm and reside as micro-colonies on vegetable
      surfaces, strengthening the notion of possible survival of H. pylori on
      vegetables for an extended period of time. Taken together, the ability of H.
      pylori to form biofilm on vegetables (a common food source for human) potentially
      plays an important role in its survival, serving as a mode of transmission of H.
      pylori in the extragastric environment.

PMID- 27889169
TI  - Characterization of biocide-tolerant bacteria isolated from cheese and dairy
      small-medium enterprises.
AB  - A collection of 120 bacterial isolates from small medium enterprises involved in
      the production of cow milk and the manufacture of goat cheese were screened for
      sensitivity to biocides benzalkonium chloride (BC), cetrimide (CT),
      hexadecylpyridinium chloride (HDP), triclosan (TC), hexachlorophene (CF) and poly
      (hexamethylen guanidinium) hydrochloride (PHMG). Nineteen isolates were selected
      according to biocide tolerance and identified by 16S rDNA sequencing as
      Lactococcus sp. (6) Enterococcus sp. (1), Lactobacillus sp. (4), Bacillus sp. (1)
      Escherichia sp. (5), Enterobacter sp. (1) and Helicobacter sp. (1). These were
      further characterised regarding antimicrobial resistance phenotype and genotype.
      Several isolates were multiply (3 or more) tolerant to biocides or resistant to
      antibiotics, but only two Escherichia sp. isolates and Enterobacter sp. were
      multiply resistant to biocides and antibiotics. Statistical analysis of biocide
      tolerance and antibiotic resistance revealed significant positive correlations
      between different biocides and between biocides and antibiotics. The biocide
      tolerance genes most frequently found were qacEDelta1 and qacA/B. The sulfonamide
      resistance gene sul1 was found in two Escherichia sp. isolates and in
      Enterobacter sp., all of which also carried qacEDelta1. Beta-lactam (blaCTX-M,
      blaPSE) and tetracycline resistance genes [tet(A), tet(C) and tet(D)] were
      detected. Efflux pump genes acrB and mdfA were found in most Gram-negative
      isolates. Results from the study suggest that exposure to biocides can indirectly
      select for antibiotic resistance.

PMID- 27889170
TI  - Drying parameters greatly affect the destruction of Cronobacter sakazakii and
      Salmonella Typhimurium in standard buffer and milk.
AB  - Salmonella Typhimurium and Cronobacter sakazakii are two foodborne pathogens
      involved in neonatal infections from milk powder and infant formula. Their
      ability to survive in low-moisture food and during processing from the
      decontamination to the dried state is a major issue in food protection. In this
      work, we studied the effects of the drying process on Salmonella Typhimurium and
      Cronobacter sakazakii, with the aim of identifying the drying parameters that
      could promote greater inactivation of these two foodborne pathogens. These two
      bacteria were dried under different atmospheric relative humidities in milk and
      phosphate-buffered saline, and the delays in growth recovery and cultivability
      were followed. We found that water activity was related to microorganism
      resistance. C. sakazakii was more resistant to drying than was S. Typhimurium,
      and milk increased the cultivability and recovery of these two species. High
      drying rates and low final water activity levels (0.11-0.58) had a strong
      negative effect on the growth recovery and cultivability of these species. In
      conclusion, we suggest that effective use of drying processes may provide a
      complementary tool for food decontamination and food safety during the production
      of low-moisture foods.

PMID- 27889171
TI  - Antifungal activity of beta-carbolines on Penicillium digitatum and Botrytis
      cinerea.
AB  - beta-carbolines (betaCs) are alkaloids widely distributed in nature that have
      demonstrated antimicrobial properties. Here, we tested in vitro six betaCs
      against Penicillium digitatum and Botrytis cinerea, causal agents of postharvest
      diseases on fruit and vegetables. Full aromatic betaCs (harmine, harmol,
      norharmane and harmane) exhibited a marked inhibitory effect on conidia
      germination at concentrations between 0.5 and 1 mM, while dihydro-betaCs
      (harmalina and harmalol) only caused germination delay. Harmol showed the highest
      inhibitory effect on both fungal pathogens. After 24 h of exposure to 1 mM
      harmol, conidia revealed a severe cellular damage, exhibiting disorganized
      cytoplasm and thickened cell wall. Harmol antimicrobial effect was fungicidal on
      B. cinerea, while it was fungistatic on P. digitatum. Conidia membrane
      permeabilization was detected in treatments with harmol at sub-inhibitory and
      inhibitory concentrations, for both pathogens. In addition, residual infectivity
      of P. digitatum on lemons and B. cinerea on blueberries was significantly reduced
      after exposure to this alkaloid. It also inhibited mycelial growth, preventing
      sporulation at the highest concentration tested. These results indicate that
      harmol might be a promising candidate as a new antifungal molecule to control
      causal agents of fruit diseases.

PMID- 27889172
TI  - Safety assessment of Tetragenococcus halophilus isolates from doenjang, a Korean
      high-salt-fermented soybean paste.
AB  - We assessed the safety of 49 Tetragenococcus halophilus strains isolated from
      doenjang in Korea. Minimum inhibitory concentration assays showed that all
      strains can be considered as susceptible to ampicillin, erythromycin, penicillin
      G, tetracycline, and vancomycin, but resistant to ciprofloxacin based on the
      Enterococcus breakpoint values provided by the European Committee on
      Antimicrobial Susceptibility testing in 2015. Ciprofloxacin resistance was
      sufficiently high to consider the potential for acquisition of transmissible
      determinants. Two strains exhibiting potentially acquired resistance to
      chloramphenicol and gentamicin, and chloramphenicol alone, were identified. None
      of the strains exhibited alpha-hemolytic activity or biofilm formation; two
      strains exhibited weak beta-hemolytic activity. Doenjang isolates produced an
      average of 3338.6 ppm of tyramine in the laboratory, considerably higher than the
      levels produced by two reference strains. All of the test strains exhibited
      similar cadaverine, histamine, and putrescine production patterns. Most T.
      halophilus strains could grow at a NaCl concentration >18%, exhibited acid
      production at 15% NaCl, and expressed strain-specific protease and lipase
      activities. The potential acquisition of transmissible determinants for
      antibiotic resistance and tyramine production identified in this study
      necessitate the need for a thorough safety assessment of T. halophilus before it
      can be considered for use in food fermentation processes.

PMID- 27889173
TI  - Variability in the adaptive acid tolerance response phenotype of Salmonella
      enterica strains.
AB  - The objective of this study was the assessment of the stationary-phase, low-pH
      inducible acid tolerance response (ATR) of different Salmonella enterica strains.
      For this purpose, 30 strains of the pathogen were grown in tryptone soy broth in
      the absence (non-adapted cultures) and presence (1% w/v; acid-adapted cultures)
      of glucose, and then subjected to 4-h acid challenge trials at pH 3.0. Surviving
      populations of each strain were determined at 1-h intervals, and the Weibull
      model was fitted to the derived microbiological data. Extensive variability in
      the acid stress responses of the tested S. enterica strains was observed, with
      the total population reductions (log CFU/ml) attained in 4 h of acid challenge
      ranging from 0.9 to 5.5 and from 0.6 to 7.0 for the non-adapted and acid-adapted
      cultures, respectively. As demonstrated by the model scale parameter delta and
      shape parameter p, the effect of acid adaptation on the inactivation curves was
      strain-specific. Although acid adaptation resulted in enhanced acid survival for
      the majority of the tested strains, there were strains exhibiting similar or
      decreased acid resistance compared to their non-adapted counterparts. Moreover,
      acid adaptation appeared to decrease the strain variability of delta whereas
      increasing the strain variability of p: the coefficient of variation of delta
      among the tested strains was 97.2 and 54.9% for the non-adapted and acid-adapted
      cultures, respectively, while the corresponding values for p were 12.7 and 48.1%.
      The data of the present study, which is the first one to systematically evaluate
      the adaptive ATR of multiple S. enterica strains, clearly demonstrate that this
      phenotype (attempted to be induced by growing the pathogen in the presence of
      glucose) is strain-dependent.

PMID- 27889174
TI  - ?

PMID- 27889175
TI  - Inhibition of Adenylyl Cyclase in the Spinal Cord Alleviates Painful Diabetic
      Neuropathy in Zucker Diabetic Fatty Rats.
AB  - OBJECTIVES: Diabetic neuropathy is the most common complication of both type 1
      and type 2 diabetes. In this study, we tested the hypotheses that impaired Gi
      protein expression/function in the spinal cord is associated with the development
      of painful neuropathy in people with type 2 diabetes and that reduction of cyclic
      adenosine monophosphate (cAMP) production by inhibiting adenylyl cyclase in the
      spinal cord can alleviate diabetic neuropathy. METHODS: To this end, we examined
      the levels of cAMP, cAMP-dependent protein kinase (PKA) and cAMP response element
      binding protein (CREB) in the spinal cord after the development of neuropathic
      pain in Zucker diabetic fatty (ZDF) rats with type 2 diabetes. We evaluated the
      effects of intrathecal injections of SQ22536, an adenylyl cyclase inhibitor, on
      mechanical allodynia and thermal hyperalgesia in rats with painful diabetic
      neuropathy. RESULTS: We found that diabetic ZDF rats exhibited mechanical
      allodynia and thermal hyperalgesia, which are associated with enhanced cAMP
      production, increased PKA activation and elevated CREB phosphorylation in the
      spinal cord. Additionally, diabetic ZDF rats exhibited attenuated expression of
      Gialpha, but not Gsalpha, in the spinal cord. Furthermore, intrathecal
      administrations of SQ22536 dose-dependently alleviated mechanical allodynia and
      thermal hyperalgesia in diabetic ZDF rats and reduced cAMP production, PKA
      activation and p-CREB expression in the spinal cord. CONCLUSIONS: Taken together,
      our study suggested that cAMP-mediated signalling in the spinal cord is likely
      critical for the development of painful neuropathy in people with type 2
      diabetes.

PMID- 27889176
TI  - [Oncocytoma with a thrombus into the renal vein: A case report].

PMID- 27889177
TI  - [Assessment of the learning curves for intravesical adenoma morcellation using
      Piranha(c) device during endoscopic enucleation].
AB  - INTRODUCTION: Morcellation of intravesical adenoma (MIA) is an important part of
      the endoscopic enucleation procedure. The aim of this study was to analyse the
      learning curve of the MIA during endoscopic enucleation of the prostate.
      MATERIAL: We conducted a prospective study of the first 90 patients treated by
      endoscopic enucleation of the prostate by a single surgeon without previous
      experience of MIA. The population was divided into 3 consecutive groups of 30
      patients. MIA was performed with the morcellator Pinranha (Wolf) and disposable
      blades (Vmax(c)). The criteria selected to assess the progress of MIA over time
      were: duration of MIA (min), the intraoperative complications encountered during
      MIA and weight morcelleted tissue. The efficacy of MIA was assessed with the
      ratio weight specimen/MIA duration (min/g) over time. RESULTS: The three groups
      were comparable in terms of age, ASA score of prostate volume. A significant
      decrease in the duration of MIA was found between groups 1 and 2 (12 versus
      5.5min, P<0.0001), to reach a plateau in the group 3 (3min). A significant
      increase in the efficiency of MIA was found between group 1 and 2 (5.5 versus
      11g/min, P<0.0001), to reach a plateau in the group 3 (20g/min). Bladder injuries
      were limited (7.7%), superficial and encountered in the early learning phase.
      CONCLUSION: In our experience, the MIA required a learning curve estimated
      between 30 and 60 procedures. LEVEL OF EVIDENCE: IV.

PMID- 27889178
TI  - Comparison with adsorption of Re (VII) by two different gamma-radiation
      synthesized silica-grafting of vinylimidazole/4-vinylpyridine adsorbents.
AB  - Two silica gel based adsorbents for Re (VII), i.e. SS-MPTS-VIMH and SS-MPTS-VPQ,
      were synthesised. Silica gel was used as the matrix for gamma-radiation grafting,
      and the monomer of 1-vinyl imidazole (VIM) and 4-vinylpyridine (4-VP) was grafted
      onto the silica silanized by methacryloxy propyl trimethoxyl silane,
      respectively. A VIM concentration of 2molL-1 and an absorbed dose of 30kGy were
      the optimal grafting conditions for adsorbent SS-MPTS-VIM, and a 4-VP
      concentration of 4molL-1 and an absorbed dose of 40kGy were the optimal grafting
      conditions for adsorbent SS-MPTS-VP. At the certain condition, the grafting yield
      of SS-MPTS-VIM was 30.1% and that of SS-MPTS-VP was 21.0%. The adsorption
      capacity of adsorbent SS-MPTS-VIMH was 145.99mgg-1 and that of SS-MPTS-VPQ was
      71.08mgg-1 according to the Langmuir model. The adsorbent SS-MPTS-VPQ had better
      adsorption properties of acid resistance and anti-interference than SS-MPTS-VIMH.
      Dynamic column experiments showed that protonated adsorbent SS-MTPS-VIMH could be
      recycled with good performance while quaternized adsorbent SS-MPTS-VPQ could not.
      The adsorbent SS-MPTS-VIMH belongs to weak anion exchange adsorbent and SS-MPTS
      VPQ belongs to strong anion exchange adsorbent. This study paves a way to the
      synthesis and application of a novel silica base adsorbents for Re (VII).

PMID- 27889179
TI  - Estimation of rate constants of PCB dechlorination reactions using an anaerobic
      dehalogenation model.
AB  - This study aims to estimate anaerobic dechlorination rate constants (km) of
      reactions of individual PCB congeners using data from four laboratory microcosms
      set up using sediment from Baltimore Harbor. Pathway km values are estimated by
      modifying a previously developed model as Anaerobic Dehalogenation Model (ADM)
      which can be applied to any halogenated hydrophobic organic (HOC). Improvements
      such as handling multiple dechlorination activities (DAs) and co-elution of
      congeners, incorporating constraints, using new goodness of fit evaluation led to
      an increase in accuracy, speed and flexibility of ADM. DAs published in the
      literature in terms of chlorine substitutions as well as specific microorganisms
      and their combinations are used for identification of pathways. The best fit
      explaining the congener pattern changes was found for pathways of Phylotype
      DEH10, which has the ability to remove doubly flanked chlorines in meta and para
      positions, para flanked chlorines in meta position. The range of estimated km
      values is between 0.0001-0.133d-1, the median of which is found to be comparable
      to the few available published biologically confirmed rate constants. Compound
      specific modelling studies such as that performed by ADM can enable monitoring
      and prediction of concentration changes as well as toxicity during
      bioremediation.

PMID- 27889180
TI  - Rapid restoration of methanogenesis in an acidified UASB reactor treating 2,4,6
      trichlorophenol (TCP).
AB  - Anaerobic bioreactors are often used for removal of xenobiotic and highly toxic
      pollutants from wastewater. Most of the time, the pollutant is so toxic that the
      stability of the reactor becomes compromised. It is well known that methanogens
      are one of the most sensitive organisms in the anaerobic consortia and hence the
      stability of the reactors is highly dependant on methanogenesis. Unfortunately
      few studies have focused on recovering the methanogenic activity once it has been
      inhibited by highly toxic pollutants. Here we establish a quick recovery strategy
      for neutralization of an acidified UASB reactor after failure by intoxication
      with an excess of TCP in the influent. Once the reactor returned to pH values
      compatible with methanogenesis, biogas production was re-started after one day
      and the system was re-acclimated to TCP. Successful removal of TCP from synthetic
      wastewater was shown for concentrations up to 70mg/L after restoration.

PMID- 27889181
TI  - Brazilian Cerrado soil reveals an untapped microbial potential for unpretreated
      polyethylene biodegradation.
AB  - Discarded PE-based products pose a social and environmental threat because of
      their recalcitrance to degradation, a consequence of the unique set of PE's
      physicochemical properties. In this study we isolated nine novel PE-degrading
      bacteria from plastic debris found in soil of the savanna-like Brazilian Cerrado.
      These bacterial strains from the genera Comamonas, Delftia, and Stenotrophomonas
      showed metabolic activity and cellular viability after a 90-day incubation with
      PE as the sole carbon source. ATR/FTIR indicated that biodegraded PE undergone
      oxidation, vinylene formation, chain scission, among other chemical changes.
      Considerable nanoroughness shifts and vast damages to the micrometric surface
      were confirmed by AFM and SEM. Further, phase imaging revealed a 46.7% decrease
      in the viscous area of biodegraded PE whereas Raman spectroscopy confirmed a loss
      in its crystalline content, suggesting the assimilation of smaller fragments.
      Intriguingly, biodegraded PE chemical fingerprint suggests that these strains use
      novel biochemical strategies in the biodegradation process. Our results indicate
      that these microbes are capable of degrading unpretreated PE of very high
      molecular weight (191,000gmol-1) and survive for long periods under this
      condition, suggesting not only practical applications in waste management and
      environmental decontamination, but also future directions to understand the
      unraveled metabolism of synthetic polymers.

PMID- 27889182
TI  - Development of polyethyleneimine-loaded core-shell chitosan hollow beads and
      their application for platinum recovery in sequential metal scavenging fill-and
      draw process.
AB  - Polyethyleneimine (PEI)-loaded chitosan hollow beads (CHBs) were fabricated
      through the ionotropic gelation process using sodium tripolyphosphate (TPP) as a
      counter polyanion. The CHBs were loaded with hydrophilic PEI in pre- and/or post
      loading methods. Hence, the sorbent could possess a large number of amine groups
      which were able to function as the binding sites to recover platinum metal ions.
      The enhancement of the amine groups was confirmed by Fourier transform infrared
      spectroscopy (FTIR). Isotherm and kinetic studies were carried out to evaluate
      the sorption performance of the sorbents. The maximum Pt(IV) uptake by the PEI
      loaded CHBs was estimated to be 815.2+/-72.6mg/g, which was much higher than that
      of a commercial ion exchange resin, Lewatit(r) MonoPlus TP214 (330.2+/-16.6mg/g).
      A sequential metal scavenging fill-and-draw process was operated using the PEI
      loaded CHBs sorbents for ten cycles and the Pt(IV) recovery efficiency was kept
      above 97.4% even after the last cycle. These results indicated that the ionic
      polymer-loaded hydrogel hollow beads can be a novel platform to design high
      performance sorbents able to recover and/or scavenge anionic precious metal ions
      even from trace metal solutions.

PMID- 27889183
TI  - Increase of cytotoxicity during wastewater chlorination: Impact factors and
      surrogates.
AB  - Toxic and harmful disinfection byproducts (DBPs) were formed during wastewater
      chlorination. It was recently suggested that cytotoxicity to mammalian cells
      reflects risks posed by chlorinated wastewater. Here, ATP assays were performed
      to evaluate the cytotoxicity to mammalian cells. Chlorination significantly
      increased cytotoxicity of treated wastewater. Factors affecting cytotoxicity
      formation during wastewater chlorination were investigated. Quenching with sodium
      thiosulfate and ascorbic acid decreased the formed cytotoxicity, while ammonium
      kept the cytotoxicity stable. The chlorine dose required for the maximum
      cytotoxicity increase was dramatically affected by DOC and ammonia
      concentrations. The maximum cytotoxicity increase, defined as the cytotoxicity
      formation potential (CtFP), occurred when wastewater was treated for 48h with a
      chlorine dose of 2.DOC+11.NH3N+10 (mg-Cl2/L). During chlorination, the amounts of
      AOX formation was found to be significantly correlated with cytotoxicity
      formation when no DBPs were destroyed. AOX formation could be used as a surrogate
      to estimate cytotoxicity increase during wastewater chlorination. Besides, the
      CtFP of 14 treated wastewater samples was assessed ranged from 5.4-20.4mg
      phenol/L. The CtFP could be estimated from UV254 of treated wastewater because
      CtFP and UV254 were strongly correlated.

PMID- 27889184
TI  - GEC-ESTRO ACROP recommendations for head & neck brachytherapy in squamous cell
      carcinomas: 1st update - Improvement by cross sectional imaging based treatment
      planning and stepping source technology.
AB  - The Head and Neck Working Group of the GEC-ESTRO (Groupe Europeen de
      Curietherapie - European Society for Therapeutic Radiology and Oncology)
      published in 2009 the consensus recommendations for low-dose rate, pulsed-dose
      rate and high-dose rate brachytherapy in head & neck cancers. The use of
      brachytherapy in combination with external beam radiotherapy and/or surgery was
      also covered as well as the use of brachytherapy in previously irradiated
      patients. Given the developments in the field, these recommendations needed to be
      updated to reflect up-to-date knowledge. The present update does not repeat basic
      knowledge which was published in the first recommendation but covers in a general
      part developments in (1) dose and fractionation, (2) aspects of treatment
      selection for brachytherapy alone versus combined BT+EBRT and (3) quality
      assurance issues. Detailed expert committee opinion intends to help the clinical
      practice in lip-, oral cavity-, oropharynx-, nasopharynx-, and superficial
      cancers. Different aspects of adjuvant treatment techniques and their results are
      discussed, as well the possibilities of salvage brachytherapy applications.

PMID- 27889185
TI  - NUP98 Fusion Proteins Interact with the NSL and MLL1 Complexes to Drive
      Leukemogenesis.
AB  - The nucleoporin 98 gene (NUP98) is fused to a variety of partner genes in
      multiple hematopoietic malignancies. Here, we demonstrate that NUP98 fusion
      proteins, including NUP98-HOXA9 (NHA9), NUP98-HOXD13 (NHD13), NUP98-NSD1, NUP98
      PHF23, and NUP98-TOP1 physically interact with mixed lineage leukemia 1 (MLL1)
      and the non-specific lethal (NSL) histone-modifying complexes. Chromatin
      immunoprecipitation sequencing illustrates that NHA9 and MLL1 co-localize on
      chromatin and are found associated with Hox gene promoter regions. Furthermore,
      MLL1 is required for the proliferation of NHA9 cells in vitro and in vivo.
      Inactivation of MLL1 leads to decreased expression of genes bound by NHA9 and
      MLL1 and reverses a gene expression signature found in NUP98-rearranged human
      leukemias. Our data reveal a molecular dependency on MLL1 function in NUP98
      fusion-driven leukemogenesis.

PMID- 27889186
TI  - Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis.
AB  - Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type
      mice following a mechanism very similar to that observed in obese humans. The
      process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses
      to steatohepatitis and fibrosis before HCC detection. This pathophysiological
      pathway is driven by jet-lag-induced genome-wide gene deregulation and global
      liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile
      acid and xenobiotic metabolism among the top deregulated pathways. Ablation of
      farnesoid X receptor dramatically increases enterohepatic bile acid levels and
      jet-lag-induced HCC, while loss of constitutive androstane receptor (CAR), a well
      known liver tumor promoter that mediates toxic bile acid signaling, inhibits
      NAFLD-induced hepatocarcinogenesis. Circadian disruption activates CAR by
      promoting cholestasis, peripheral clock disruption, and sympathetic dysfunction.

PMID- 27889187
TI  - Maternal Polycystic Ovary Syndrome and Risk for Attention-Deficit/Hyperactivity
      Disorder in the Offspring.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common
      childhood neurodevelopmental disorder, and boys are two to three times more
      likely to develop ADHD. Maternal polycystic ovary syndrome (PCOS), a common
      metabolic disorder associated with excess circulating androgens, has been
      associated with increased risk for autism spectrum disorder in the offspring. In
      this study, we aimed to investigate whether maternal PCOS increases the risk for
      ADHD in the offspring. METHODS: We conducted a matched case-control study using
      health and population data registers for all children born in Sweden from 1984 to
      2008. Maternal PCOS was defined by ICD-coded register diagnosis. The outcome of
      ADHD was defined as an ICD-coded register diagnosis of ADHD and/or registered
      prescription of medications to treat ADHD. A total of 58,912 ADHD cases (68.8%
      male) were identified and matched to 499,998 unaffected controls by sex and birth
      month and year. RESULTS: Maternal PCOS increased the odds of offspring ADHD by
      42% after adjustment for confounders (odds ratio [OR], 1.42; 95% confidence
      interval [CI], 1.26-1.58). Exclusion of ADHD cases with comorbid autism spectrum
      disorder attenuated but did not explain the relationship (OR, 1.34; 95% CI, 1.18
      1.52). The risk was somewhat elevated for ADHD with comorbid autism spectrum
      disorder (OR, 1.76; 95% CI, 1.37-2.26). The risk for ADHD was higher among obese
      mothers with PCOS (OR, 1.68; 95% CI, 1.31-2.17) and was highest among obese
      mothers with PCOS and other features of metabolic syndrome (OR, 2.59; 95% CI,
      1.02-6.58). CONCLUSIONS: This study provides evidence that maternal PCOS may
      subtly influence the neurodevelopment of the offspring, resulting in increased
      risk for neurodevelopmental disorders such as ADHD.

PMID- 27889188
TI  - Dynamic margin of stability during gait is altered in persons with multiple
      sclerosis.
AB  - Persons with multiple sclerosis (PwMS) have high fall risk due to altered
      balance. To measure dynamic balance during walking, margin of stability (MoS)
      examines how the extrapolated center of mass moves relative to the base of
      support. This study investigates how MoS is affected in PwMS during walking at
      preferred, slow, and fast speeds, as well as the relationship between MoS and the
      Expanded Disability Severity Score (EDSS), fall history, and self-report balance
      confidence questionnaire. MoS was evaluated in PwMS without clinical gait
      impairment (MS1; n=20), PwMS with clinical gait impairment (MS2; n=20), and age
      matched healthy controls (HC) (n=20), in the anterior/posterior (AP) and
      medial/lateral (ML) direction at heel strike and midstance. In the AP direction,
      MS2 had a higher MoS than HC (p<0.001) and MS1 (p<0.001) at heel strike and
      midstance. In the ML direction, MS2 had a higher MoS than HC (p<0.001) at heel
      strike only. At midstance, slow pace had a lower MoS than preferred pace
      (p<0.001) and fast pace (p=0.007). Compared to HC, PwMS walk slower which
      increases their AP MoS. In the ML direction, slow walking causes lower MoS at
      midstance, so PwMS increase their MoS by taking wider steps. AP MoS correlated
      with EDSS (p=0.008) and number of falls (p=0.001), and ML MoS correlated with
      number of falls (p=0.027). Walking slower, with shorter step length, and with
      wider step widths increases MoS for PwMS but may be a poor adaptive gait strategy
      since falls still occur.

PMID- 27889189
TI  - Reliability of gait analysis using wearable sensors in patients with knee
      osteoarthritis.
AB  - The aim of this study was to determine the test-retest reliability of linear
      acceleration waveforms collected at the low back, thigh, shank, and foot during
      walking, in a cohort of knee osteoarthritis patients, by applying two separate
      sensor attitude correction methods (static attitude correction and dynamic
      attitude correction). Linear acceleration data were collected on the subjects'
      most affected limb during treadmill walking on two separate days. Results reveal
      all attitude corrected acceleration waveforms displayed high repeatability, with
      coefficient of multiple determination values ranging from 0.82 to 0.99. Overall,
      mediolateral accelerations and the thigh sensor demonstrated the lowest
      reliabilities, but interaction effects revealed only mediolateral accelerations
      at the thigh and foot sensors were different than other axes and sensor
      locations. Both attitude correction methods led to improved reliability of linear
      acceleration waveforms. These findings suggest that while all sensor locations
      and axes display acceptable reliability in a clinical knee osteoarthritis
      population, the back and shank locations, and the vertical and anteroposterior
      acceleration directions, are most reliable.

PMID- 27889190
TI  - Diagnosis of multiple sclerosis: progress and challenges.
AB  - The diagnosis of multiple sclerosis is based on neurological symptoms and signs,
      alongside evidence of dissemination of CNS lesions in space and time. MRI is
      often sufficient to confirm the diagnosis when characteristic lesions accompany a
      typical clinical syndrome, but in some patients, further supportive information
      is obtained from cerebrospinal fluid examination and neurophysiological testing.
      Differentiation is important from other diseases in which demyelination is a
      feature (eg, neuromyelitis optica spectrum disorder and acute disseminated
      encephalomyelitis) and from non-demyelinating disorders such as chronic small
      vessel disease and other inflammatory, granulomatous, infective, metabolic, and
      genetic causes that can mimic multiple sclerosis. Advances in MRI and serological
      and genetic testing have greatly increased accuracy in distinguishing multiple
      sclerosis from these disorders, but misdiagnosis can occur. In this Series paper
      we explore the progress and challenges in the diagnosis of multiple sclerosis
      with reference to diagnostic criteria, important differential diagnoses,
      controversies and uncertainties, and future prospects.

PMID- 27889191
TI  - Progressive multiple sclerosis: prospects for disease therapy, repair, and
      restoration of function.
AB  - Multiple sclerosis is a major cause of neurological disability, which accrues
      predominantly during progressive forms of the disease. Although development of
      multifocal inflammatory lesions is the underlying pathological process in
      relapsing-remitting multiple sclerosis, the gradual accumulation of disability
      that characterises progressive multiple sclerosis seems to result more from
      diffuse immune mechanisms and neurodegeneration. As a result, the 14 anti
      inflammatory drugs that have regulatory approval for treatment of relapsing
      remitting multiple sclerosis have little or no efficacy in progressive multiple
      sclerosis without inflammatory lesion activity. Effective therapies for
      progressive multiple sclerosis that prevent worsening, reverse damage, and
      restore function are a major unmet need. In this Series paper we summarise the
      current status of therapy for progressive multiple sclerosis and outline
      prospects for the future.

PMID- 27889192
TI  - Evolving concepts in the treatment of relapsing multiple sclerosis.
AB  - In the past 20 years the treatment scenario of multiple sclerosis has radically
      changed. The increasing availability of effective disease-modifying therapies has
      shifted the aim of therapeutic interventions from a reduction in relapses and
      disability accrual, to the absence of any sign of clinical or MRI activity. The
      choice for therapy is increasingly complex and should be driven by an appropriate
      knowledge of the mechanisms of action of the different drugs and of their risk
      benefit profile. Because the relapsing phase of the disease is characterised by
      inflammation, treatment should be started as early as possible and aim to re
      establish the normal complex interactions in the immune system. Before starting a
      treatment, neurologists should carefully consider the state of the disease, its
      prognostic factors and comorbidities, the patient's response to previous
      treatments, and whether the patient is likely to accept treatment-related risks
      in order to maximise benefits and minimise risks. Early detection of suboptimum
      responders, thanks to accurate clinical monitoring, will allow clinicians to
      redesign treatment strategies where necessary.

PMID- 27889193
TI  - Do Not Hedge When There Is Certainty.

PMID- 27889194
TI  - Usefulness of Thromboelastography in the Detection and Management of Tissue
      Plasminogen Activator-Associated Hyperfibrinolysis.
AB  - Rotation thromboelastometry is a viscoelastometric method that provides a rapid
      assessment of a patient's hemostatic processes in emergency settings, allowing
      prompt identification of specific coagulation abnormalities. Its results thus
      might guide targeted replacement therapy in hemorrhagic conditions, in case of
      platelet or coagulation factor deficiency, or hyperfibrinolysis, which is
      difficult to identify otherwise. Although currently used in emergency and
      traumatic surgery, there are limited data about thromboelastometry in ischemic
      stroke, particularly in monitoring the coagulative response to recombinant tissue
      plasminogen activator after intravenous thrombolysis (IVT). Here we report a case
      of ischemic stroke complicated by a remote asymptomatic intracranial hemorrhage
      after IVT and additional endovascular therapy that has been successfully treated
      with intravenous infusion of tranexamic acid after the detection of the status of
      hyperfibrinolysis provided by thromboelastometry. Further studies are needed to
      provide the potential usefulness of thromboelastometry and tranexamic acid in
      ischemic stroke complicated by intracranial bleeding.

PMID- 27889195
TI  - Metastasectomy in cutaneous melanoma.
AB  - Metastasectomy remains the only treatment in malignant melanoma to offer complete
      pathologic response within a few days of in-hospital stay. It has been
      historically associated with the highest survival rates in the literature
      reported for patients of this stage. However, only a minority of patients are
      amenable to curative resection of distant metastatic disease. This patient group
      exhibit slow growing oligometastases as indicated by: a. Long disease free
      interval after treatment of their primary tumours and b. An exhaustive
      preoperative work up with the use of PET/CT and MRI scans. Only complete
      resection of all metastases is associated with long term survival and debulking
      should not be attempted. Metastasectomy has also been shown to offer significant
      palliation in cases of gastrointestinal bleeding or obstruction. The timing and
      the sequencing of surgery in the modern multimodal targeted treatment of melanoma
      is still unclear and warrants further investigation.

PMID- 27889198
TI  - Authors' Response: Expression of CD56 in patients with adenomyosis and its
      correlation with dysmenorrhea.

PMID- 27889196
TI  - Impact of molecular subtypes classification concordance between preoperative core
      needle biopsy and surgical specimen on early breast cancer management: Single
      institution experience and review of published literature.
AB  - BACKGROUND: Core needle biopsy (CNB) plays a crucial role as diagnostic tool for
      breast cancer (BC). The characterization of biomarkers status before surgical
      treatment is crucial when primary systemic therapy is a therapeutic option. The
      aim of this analysis was to report concordance between preoperative CNB and
      surgical specimen (SS) in evaluating biomarkers and molecular subtypes. METHODS:
      Data have been collected from a cohort of 101 patients affected by early BC
      treated at Careggi Florence University Hospital, between January 2014 and March
      2015. The conformity between molecular subtype classification was tested using
      kappa (kappa) test. RESULTS: Mean age was 57.5 years (range 29-86). There was
      concordance between the estrogen receptor (ER) assessment on CNB and SS in 95
      cases (94.1%). Concordance of the progesterone receptor (PgR) assessment was
      observed in 89 cases (88.1%). Concordance for detecting immunohistochemistry
      assessed BC molecular subtypes was 87.1% (kappa = 0.78). Concerning Ki-67
      evaluation, we report a concordance rate of 88.1% (kappa = 0.68). The evaluation
      of luminal A plus luminal B/HER negative subgroup showed a kappa-value of 0.65.
      CONCLUSIONS: CNB showed good accuracy in evaluating hormonal receptors status,
      HER2, and BC molecular subtypes. Evaluation of Ki67 status was less accurate than
      other biomarkers; therefore, we recommend that it should be detected both on CNB
      and SS samples, especially in hormonal positive HER2 negative tumors, in order to
      avoid a misclassification of tumor subtypes that could lead to an omission of
      potential effective systemic therapy.

PMID- 27889197
TI  - Complication-related removal of totally implantable venous access port systems:
      Does the interval between placement and first use and the neutropenia-inducing
      potential of chemotherapy regimens influence their incidence? A four-year
      prospective study of 4045 patients.
AB  - BACKGROUND: Totally implantable venous access port systems are widely used in
      oncology, with frequent complications that sometimes necessitate device removal.
      The aim of this study is to investigate the impact of the time interval between
      port placement and initiation of chemotherapy and the neutropenia-inducing
      potential of the chemotherapy administered upon complication-related port
      removal. PATIENTS AND METHODS: Between January 2010 and December 2013, 4045
      consecutive patients were included in this observational, single-center
      prospective study. The chemotherapy regimens were classified as having a low
      (<10%), intermediate (10-20%), or high (>20%) risk for inducing neutropenia.
      RESULTS: The overall removal rate due to complications was 7.2%. Among them, port
      related infection (2.5%) and port expulsion (1%) were the most frequent. The
      interval between port insertion and its first use was shown to be a predictive
      factor for complication-related removal rates. A cut-off of 6 days was
      statistically significant (p = 0.008), as the removal rate for complications was
      9.4% when this interval was 0-5 days and 5.7% when it was >=6 days. Another
      factor associated with port complication rate was the neutropenia-inducing
      potential of the chemotherapy regimens used, with removal for complications
      involved in 5.5% of low-risk regimens versus 9.4% for the intermediate- and high
      risk regimens (p = 0.003). CONCLUSION: An interval of 6 days between placement
      and first use of the port reduces the removal rate from complications. The
      intermediate- and high-risk for neutropenia chemotherapy regimens are related to
      higher port removal rates from complications than low-risk regimens.

PMID- 27889199
TI  - Use of a laparoscopic specimen retrieval bag for delivery of an entrapped head in
      a breech fetus at 21 weeks gestation.

PMID- 27889200
TI  - Oral tuberculosis.

PMID- 27889201
TI  - Expression of Fibroblast Activating Protein and Correlation with Histological
      Grade, Mitotic Index and Ki67 Expression in Canine Mast Cell Tumours.
AB  - Fibroblast activating protein (FAP) is a membrane serine protease expressed by
      activated fibroblasts, particularly tumour associated fibroblasts (TAFs). FAP
      expression has not been reported in canine mast cell tumours (MCTs). The
      objective of this study was to evaluate the expression of FAP in TAFs and its
      correlation with histological grade, mitotic index and Ki67 expression in canine
      MCTs. FAP expression was evaluated by immunohistochemistry (IHC) in 30 canine
      MCTs. Twenty-eight (90%) of the MCTs expressed FAP in the stroma, 16 cases showed
      low to intermediate FAP score and 14 cases had a high FAP score. FAP was
      correlated positively with both Patnaik (P = 0.007) and Kiupel (P = 0.008)
      grading systems, mitotic index (P = 0.0008) and Ki67 expression (P = 0.009). High
      stromal FAP expression could be a potential negative prognostic factor in canine
      MCTs.

PMID- 27889202
TI  - Analysis of the Elective Treatment Process for Critical Limb Ischaemia with
      Tissue Loss: Diabetic Patients Require Rapid Revascularisation.
AB  - OBJECTIVES: The number of elderly people is increasing; inevitably, the result
      will be more patients with critical limb ischaemia (CLI) in the future. Tissue
      loss in CLI is related to a high risk of major amputation. The aim of this study
      was to analyze the treatment process from referral to revascularisation, to
      discover possible delays and reasons behind them, and to distinguish patients
      benefitting the most from early revascularisation. METHODS: A retrospective
      analysis was performed of 394 consecutive patients with a combined 447 affected
      limbs, referred to the outpatient clinic during 2010-2011 for tissue loss of
      suspected ischaemic origin. RESULTS: For 246 limbs revascularisation was
      scheduled. After changes in the initial treatment strategy, endovascular
      treatment (ET) was performed on 221 and open surgery (OS) on 45 limbs. Notably
      there was crossover after ET in 17.0% of the procedures, and re
      revascularisations were required in 40.1% after ET and 31.1% after OS. The median
      time from referral to revascularisation was 43 days (range 1-657 days) with no
      significant difference between ET and OS. For 29 (11.8%) patients the ischaemic
      limb required an emergency operation scheduled at the first visit to the
      outpatient clinic. For 25 (10.2%) patients the situation worsened while waiting
      for elective revascularisation and an emergency procedure was performed. Diabetic
      patients formed the majority of the study population, with 159 diabetic feet
      undergoing revascularisation. In multivariate analysis, diabetes was associated
      with poor limb salvage. When revascularisation was achieved within 2 weeks, no
      difference was seen in limb salvage. However, when the delay from first visit to
      revascularisation exceeded 2 weeks, limb salvage was significantly poorer in
      diabetic patients. CONCLUSIONS: Diabetic ulcers always require vascular
      evaluation, and when ischaemia is suspected the diagnostics should be organised
      rapidly to ensure revascularisation without delay, according to this study within
      2 weeks from the first evaluation.

PMID- 27889203
TI  - Changes in Renal Anatomy After Fenestrated Endovascular Aneurysm Repair.
AB  - OBJECTIVE: To assess short- and long-term movement of renal arteries after
      fenestrated endovascular aortic repair (FEVAR). METHODS: Consecutive patients who
      underwent FEVAR at one institution with a custom-made device designed with
      fenestrations for the superior mesenteric (SMA) and renal arteries, a millimetric
      computed tomography angiography (CTA), and a minimum of 2 years' follow-up were
      included. Angulation between renal artery trunk and aorta, clock position of the
      origin of the renal arteries, distance between renal arteries and SMA, and target
      vessel occlusion were retrospectively collected and compared between the pre
      operative, post-operative (<6 months), and last (>12 months) CTA. RESULTS: From
      October 2004 to January 2014, 100 patients met the inclusion criteria and 86% of
      imaging was available for accurate analysis. Median follow-up was 27.3 months
      (22.7-50.1). There were no renal occlusions. A significant change was found in
      the value of renal trunk angulation of both renal arteries on post-operative
      compared with pre-operative CTA (17 degrees  difference upward [7.5-29], p <
      .001), but no significant change thereafter (p = .5). Regarding renal clock
      positions (7.5 degrees  of change equivalent to 15 min of renal ostial movement):
      significant anterior change was found between post-operative and pre-operative
      CTA (15 min [0-30], p = .03 on the left and 15 min [15-30], p < .001 on the
      right), without significant change thereafter (15 min [0-30], p = .18 on the left
      and 15 min [0-15] on the right, p = .28). No changes were noted on the distance
      between renal and SMA ostia (difference of 1.65 mm [1-2.5], p = .63). CONCLUSION:
      The renal arteries demonstrate tolerance to permanent changes in angulation after
      FEVAR of approximately 17 degrees  upward trunk movement and of 15-30 min ostial
      movement without adverse consequences on patency after a median of more than 2
      years' follow-up. The distance between the target vessels remained stable over
      time. These results may suggest accommodation to sizing errors and thus a
      compliance with off the shelf devices in favourable anatomies.

PMID- 27889205
TI  - Structural Analysis of Multi-component Amyloid Systems by Chemometric SAXS Data
      Decomposition.
AB  - Formation of amyloids is the hallmark of several neurodegenerative pathologies.
      Structural investigation of these complex transformation processes poses
      significant experimental challenges due to the co-existence of multiple species.
      The additive nature of small-angle X-ray scattering (SAXS) data allows for
      probing the evolution of these mixtures of oligomeric states, but the
      decomposition of SAXS data into species-specific spectra and relative
      concentrations is burdened by ambiguity. We present an objective SAXS data
      decomposition method by adapting the multivariate curve resolution alternating
      least squares (MCR-ALS) chemometric method. The approach enables rigorous and
      robust decomposition of synchrotron SAXS data by simultaneously introducing these
      data in different representations that emphasize molecular changes at different
      time and structural resolution ranges. The approach has allowed the study of
      fibrillogenic forms of insulin and the familial mutant E46K of alpha-synuclein,
      and is generally applicable to any macromolecular mixture that can be probed by
      SAXS.

PMID- 27889204
TI  - Tauroursodeoxycholic Acid Attenuates Angiotensin II Induced Abdominal Aortic
      Aneurysm Formation in Apolipoprotein E-deficient Mice by Inhibiting Endoplasmic
      Reticulum Stress.
AB  - OBJECTIVE/BACKGROUND: Abdominal aortic aneurysm (AAA) is characterised by the
      infiltration of smooth muscle cell (SMC) apoptosis, inflammatory cells,
      neovascularisation, and degradation of the extracellular matrix. Previous work
      has shown that endoplasmic reticulum (ER) stress and SMC apoptosis were increased
      both in a mouse model and human thoracic aortic aneurysm. However, whether the ER
      stress is activated in AAA formation and whether suppressing ER stress attenuates
      AAA is unknown. METHODS: Human AAA and control aorta samples were collected.
      Expression of ER stress chaperones glucose-regulated protein (GRP)-78 and GRP-94
      was detected by immunohistochemical staining. The effect of ER stress inhibitor
      tauroursodeoxycholic acid (TUDCA) on AAA formation in angiotensin (Ang) II
      induced apolipoprotein E-/- mice was explored. Elastin staining was used to
      observe the rupture of elastic fragmentation. Immunohistochemistry and Western
      blot analysis were performed, to detect the protein expression of ER stress
      chaperones and apoptosis molecules. RESULTS: There was significant upregulation
      of GRP-78 and GRP-94 in aneurysmal areas of human AAA and Ang II induced ApoE-/-
      mice (p < .05). TUDCA significantly attenuated the maximum diameters of abdominal
      aortas in Ang II induced ApoE-/- mice (p < .05). TUDCA significantly reduced
      expression of ER stress chaperones and the apoptotic cell numbers (p < .05).
      Furthermore, TUDCA significantly reduced expression of apoptosis molecules, such
      as caspase-3, caspase-12, C/EBP homologous protein, c-Jun N-terminal kinase
      activating transcription factor 4, X-box binding protein, and eukaryotic
      initiation factor 2alpha in Ang II induced ApoE-/- mice (p < .05). CONCLUSION:
      The results suggest that ER stress is involved in human and Ang II induced AAA
      formation in ApoE-/- mice. TUDCA attenuates Ang II induced AAA formation in ApoE
      /- mice by inhibiting ER stress mediated apoptosis.

PMID- 27889206
TI  - ProtLID, a Residue-Based Pharmacophore Approach to Identify Cognate Protein
      Ligands in the Immunoglobulin Superfamily.
AB  - Members of the extracellular immunoglobulin superfamily (IgSF) play a key role in
      immune regulation through the control of the co-stimulatory pathway, and have
      emerged as potent drug targets in cancers, infectious diseases, and autoimmunity.
      Despite the difficult experimental access to this class of proteins, single
      structures of ectodomains of IgSF proteins are solved with regularity. However,
      the most biologically critical challenge for this class of proteins is the
      identification of their cognate ligands that communicate intercellular signals.
      We describe a conceptually novel method, protein-ligand interface design
      (ProtLID), to identify cognate ligands from a subproteome for a given target
      receptor protein. ProtLID designs an optimal protein interface for a given
      receptor by running extensive molecular dynamics simulations of single-residue
      probes. The type and location of residue preferences establish a residue-based
      pharmacophore, which is subsequently used to find potential matches among
      candidate ligands within a subproteome.

PMID- 27889208
TI  - The BID Domain of Type IV Secretion Substrates Forms a Conserved Four-Helix
      Bundle Topped with a Hook.
AB  - The BID (Bep intracellular delivery) domain functions as secretion signal in a
      subfamily of protein substrates of bacterial type IV secretion (T4S) systems. It
      mediates transfer of (1) relaxases and the attached DNA during bacterial
      conjugation, and (2) numerous Bartonella effector proteins (Beps) during protein
      transfer into host cells infected by pathogenic Bartonella species. Furthermore,
      BID domains of Beps have often evolved secondary effector functions within host
      cells. Here, we provide crystal structures for three representative BID domains
      and describe a novel conserved fold characterized by a compact, antiparallel four
      helix bundle topped with a hook. The conserved hydrophobic core provides a rigid
      scaffold to a surface that, despite a few conserved exposed residues and
      similarities in charge distribution, displays significant variability. We propose
      that the genuine function of BID domains as T4S signal may primarily depend on
      their rigid structure, while the plasticity of their surface may facilitate
      adaptation to secondary effector functions.

PMID- 27889207
TI  - Dual Site Phosphorylation of Caspase-7 by PAK2 Blocks Apoptotic Activity by Two
      Distinct Mechanisms.
AB  - Caspases, the cysteine proteases that execute apoptosis, are tightly regulated
      via phosphorylation by a series of kinases. Although all apoptotic caspases work
      in concert to promote apoptosis, different kinases regulate individual caspases.
      Several sites of caspase-7 phosphorylation have been reported, but without
      knowing the molecular details, it has been impossible to exploit or control these
      complex interactions, which normally prevent unwanted proliferation. During
      dysregulation, PAK2 kinase plays an alternative anti-apoptotic role,
      phosphorylating caspase-7 and promoting unfettered cell growth and
      chemotherapeutic resistance. PAK2 phosphorylates caspase-7 at two sites,
      inhibiting activity using two different molecular mechanisms, before and during
      apoptosis. Phosphorylation of caspase-7 S30 allosterically obstructs its
      interaction with caspase-9, preventing intersubunit linker processing, slowing or
      preventing caspase-7 activation. S239 phosphorylation renders active caspase-7
      incapable of binding substrate, blocking later events in apoptosis. Each of these
      mechanisms is novel, representing new opportunities for synergistic control of
      caspases and their counterpart kinases.

PMID- 27889209
TI  - Structural Basis for the Subversion of MAP Kinase Signaling by an Intrinsically
      Disordered Parasite Secreted Agonist.
AB  - The causative agent of toxoplasmosis, the intracellular parasite Toxoplasma
      gondii, delivers a protein, GRA24, into the cells it infects that interacts with
      the mitogen-activated protein (MAP) kinase p38alpha (MAPK14), leading to
      activation and nuclear translocation of the host kinase and a subsequent
      inflammatory response that controls the progress of the parasite. The
      purification of a recombinant complex of GRA24 and human p38alpha has allowed the
      molecular basis of this activation to be determined. GRA24 is shown to be
      intrinsically disordered, binding two kinases that act independently, and is the
      only factor required to bypass the canonical mitogen-activated protein kinase
      activation pathway. An adapted kinase interaction motif (KIM) forms a highly
      stable complex that competes with cytoplasmic regulatory partners. In addition,
      the recombinant complex forms a powerful in vitro tool to evaluate the
      specificity and effectiveness of p38alpha inhibitors that have advanced to
      clinical trials, as it provides a hitherto unavailable stable and highly active
      form of p38alpha.

PMID- 27889211
TI  - Takotsubo cardiomyopathy associated with epinephrine use: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Takotsubo cardiomyopathy is a syndrome of transient cardiac
      dysfunction that is frequently associated with sudden emotional or physical
      stress. Epinephrine use has been implicated in precipitating Takotsubo
      cardiomyopathy in multiple case reports and case series. We sought to
      systematically review the current English literature on this association.
      METHODS: We searched relevant articles on Takotsubo cardiomyopathy associated
      with epinephrine administration and extracted data on demographic
      characteristics, clinical features, investigations and clinical outcomes.
      RESULTS: We identified total of 41 cases from 36 articles. The mean age of
      presentation was (47.07+/-15.73years) with strong female preponderance (83%,
      P=0.0001). The most common symptom at presentation was chest pain (82%). Mean
      peak troponin I level was (7.12+/-11.22ng/ml). The most common EKG abnormality
      was ST elevation, seen in 40% of patients. The most common finding on
      echocardiography was apical hypokinesis, seen in 48.78% cases. Patients younger
      than 45 were less likely to have apical cardiomyopathy (n=5/20, 25%) compared to
      patients with age >45 (n=14/21, 66%, p value 0.001, OR 0.17). The most common
      route of administration of epinephrine was intravenous (65.85%). All patients
      except one survived with complete recovery of systolic function reported in most
      cases within an average of 14.7days. CONCLUSION: Exposure to epinephrine in
      clinical practice can trigger Takotsubo cardiomyopathy, which is rapidly
      reversible with good prognosis in most cases. This review further supports the
      notion that both exogenous and endogenous catecholamines are associated with the
      pathogenesis of Takotsubo cardiomyopathy.

PMID- 27889210
TI  - Relations between circulating microRNAs (miR-21, miR-26, miR-29, miR-30 and miR
      133a), extracellular matrix fibrosis and serum markers of fibrosis in dilated
      cardiomyopathy.

PMID- 27889212
TI  - Study of the effect of the bacterial and fungal communities present in real
      wastewater effluents on the performance of fungal treatments.
AB  - The use of the ligninolytic fungi Trametes versicolor for the degradation of
      micropollutants has been widely studied. However, few studies have addressed the
      treatment of real wastewater containing pharmaceutically active compounds (PhAC)
      under non-sterile conditions. The main drawback of performing such treatments is
      the difficulty for the inoculated fungus to successfully compete with the other
      microorganisms growing in the bioreactor. In the present study, several fungal
      treatments were performed under non-sterile conditions in continuous operational
      mode with two types of real wastewater effluent, namely, a reverse osmosis
      concentrate (ROC) from a wastewater treatment plant and a veterinary hospital
      wastewater (VHW). In all cases, the setup consisted of two parallel reactors: one
      inoculated with T. versicolor and one non-inoculated, which was used as the
      control. The main objective of this work was to correlate the operational
      conditions and traditional monitoring parameters, such as laccase activity, with
      PhAC removal and the composition of the microbial communities developed inside
      the bioreactors. For that purpose a variety of biochemical and molecular biology
      analyses were performed: phospholipid fatty acids analysis (PLFA), quantitative
      PCR (qPCR) and denaturing gradient gel electrophoresis (DGGE) followed by
      sequencing. The results show that many indigenous fungi (and not only bacteria,
      which were the focus of the majority of previously published research) can
      successfully compete with the inoculated fungi (i.e., Trichoderma asperellum
      overtook T. versicolor in the ROC treatment). We also showed that the wastewater
      origin and the operational conditions had a stronger impact on the diversity of
      microbial communities developed in the bioreactors than the inoculation or not
      with T. versicolor.

PMID- 27889213
TI  - Spatiotemporal estimation of air temperature patterns at the street level using
      high resolution satellite imagery.
AB  - Although meteorological monitoring stations provide accurate measurements of Air
      Temperature (AT), their spatial coverage within a given region is limited and
      thus is often insufficient for exposure and epidemiological studies. In many
      applications, satellite imagery measures energy flux, which is spatially
      continuous, and calculates Brightness Temperature (BT) that used as an input
      parameter. Although both quantities (AT-BT) are physically related, the
      correlation between them is not straightforward, and varies daily due to
      parameters such as meteorological conditions, surface moisture, land use,
      satellite-surface geometry and others. In this paper we first investigate the
      relationship between AT and BT as measured by 39 meteorological stations in
      Israel during 1984-2015. Thereafter, we apply mixed regression models with daily
      random slopes to calibrate Landsat BT data with monitored AT measurements for the
      period 1984-2015. Results show that AT can be predicted with high accuracy by
      using BT with high spatial resolution. The model shows relatively high accuracy
      estimation of AT (R2=0.92, RMSE=1.58 degrees C, slope=0.90). Incorporating
      meteorological parameters into the model generates better accuracy (R2=0.935)
      than the AT-BT model (R2=0.92). Furthermore, based on the relatively high model
      accuracy, we investigated the spatial patterns of AT within the study domain. In
      the latter we focused on July-August, as these two months are characterized by
      relativity stable synoptic conditions in the study area. In addition, a temporal
      change in AT during the last 30years was estimated and verified using available
      meteorological stations and two additional remote sensing platforms. Finally, the
      impact of different land coverage on AT were estimated, as an example of future
      application of the presented approach.

PMID- 27889214
TI  - Stable hydrogen isotope values of lignin methoxyl groups of four tree species
      across Germany and their implication for temperature reconstruction.
AB  - Stable hydrogen isotope ratios of lignin methoxyl groups (delta2HLM values) in
      wood have been shown to mirror the delta2H signatures of precipitation
      (delta2Hprecip values). Thus, delta2HLM values were suggested to serve as a
      potential paleotemperature proxy since delta2Hprecip values are dominantly
      controlled by air temperature in the mid-latitudes. A recent study where a
      significant delta2HLM-temperature relationship was found for a European transect
      with mean annual temperatures ranging from -4 to 17 degrees C strengthened this
      assumption. However, using delta2HLM values as a paleotemperature proxy requires
      quantification of noise from site-, species- and biosynthetic-specific influences
      to determine the significance of recording smaller temperature changes. Here, we
      measured delta2HLM values of tree-ring sections covering 1981-1990 and 1991-2011
      of four different tree species (European beech, English oak, Scots pine, Norway
      spruce) at 15 sampling sites across Germany. The maximum difference in mean
      annual temperature between sample sites was 5 degrees C and all sites showed
      small temperature increases from 1981 to 1990 to 1991-2011 (mean Delta=0.7
      degrees C). For all species investigated, the maximum difference of delta2HLM
      within the tree was <10mUr or 0/00 (median values) and between trees at a single
      site was <=28mUr (median values). The general pattern of the spatial delta2HLM
      temperature relationship found for the European transect was confirmed here
      although a significant correlation was lacking. This can be explained by the
      lower spatial delta2Hprecip-temperature correlation (R2=0.39) found for sampling
      sites in this study and the delta2HLM differences between trees. Nevertheless,
      the temporal changes in delta2HLM values of European beech trees correctly
      reflected within +/-2 degrees C the temperature change at every sampling site.
      Therefore, we suggest that delta2HLM values of European beech trees have
      considerable potential for reconstructing temperature changes when applied on
      tree-ring chronologies and consider this approach particularly suited for Late
      Holocene climate studies.

PMID- 27889215
TI  - Benzotriazole-type ultraviolet stabilizers and antioxidants in plastic marine
      debris and their new products.
AB  - Ultraviolet stabilizers (UVSs) and antioxidants are the most widely used
      additives in plastics to enhance the lifetime of polymeric materials. There is
      growing interest in the roles of plastic marine debris and microplastics as
      source or vector of toxic substances to marine environment and organisms.
      However, there is limited information available on plastic associated chemicals,
      particularly additive chemicals. Therefore, to evaluate their extent of exposure
      from plastics to the marine environment, we determined UVSs and antioxidants in
      plastic debris (n=29) collected from beaches along with their corresponding new
      plastic products in markets (n=27) belonging to food, fisheries, and general use.
      Antioxidants were present at higher concentrations than UVSs in both plastic
      debris and new plastics, indicative of their high use over UVSs. Irganox 1076 and
      Irganox 1010 were more commonly used than other chemicals investigated. The
      irregular use with high concentration of additive chemicals was observed in short
      term use plastic products. Except for Irganox 1076 and UV 326, most antioxidants
      and UVSs were relatively high in new plastics compared to corresponding plastic
      marine debris, implying their potential leaching or degradation during use or
      after disposal. The present study provides quantitative information about
      additive chemicals contained in plastic marine debris and their new products.
      These results could be useful for better understanding of environmental exposure
      to hazardous chemicals through plastic pollution.

PMID- 27889216
TI  - Carbon nanotube amendment for treating dichlorodiphenyltrichloroethane and
      hexachlorocyclohexane remaining in Dong-ting Lake sediment - An implication for
      in-situ remediation.
AB  - Organochlorine pesticides (OCPs) were largely sprayed on the floodplain soils
      before the project of Returning Farmland to Lake in China, which caused
      contamination of sediment in Dong-ting Lake with dichlorodiphenyltrichloroethane
      (DDT) and hexachlorocyclohexane (HCH) and posed threats to human health and other
      organisms. In this study, single-walled carbon nanotubes (SWCNTs) and multi
      walled carbon nanotubes (MWCNTs) at different concentrations of 0.058, 0.145 and
      0.29wt% were used to manage residual DDTs and HCHs in Dong-ting Lake sediment.
      The efficacy was assessed by DDTs and HCHs deriving from the aqueous equilibrium
      experiment and uptake in semipermeable membrane devices (SPMDs). Desorption
      experiment and the quiescent flux experiment were conducted as well. The results
      showed that DDTs and HCHs were released from sediment. The p, p'-DDT was desorbed
      less readily than its metabolites and similarly alpha-HCH was desorbed less
      easily than other HCH isomers from sediment. Carbon nanotubes had great effects
      on treating DDTs and HCHs. The effectiveness of carbon nanotube amendment was
      dependent on type, dose and sediment-sorbent contact time In addition, carbon
      nanotubes being sprinkled on the surface of sediment as a cap and being injected
      into sediment as a mixture were considered as two effective ways to prevent DDTs
      and HCHs being released from sediment. Carbon nanotubes can be potentially useful
      as sorbents in in-situ remediation.

PMID- 27889217
TI  - The SIGHT questionnaire: A novel assessment tool for Satisfaction In Genital
      Hypospadias Treatment.
AB  - PURPOSE: Psychosexual development is currently underrepresented in hypospadias
      outcome research. The aim of this study was to develop and validate a
      questionnaire addressing psychosexual long-term satisfaction, specifically of
      adolescent patients, after hypospadias repair. MATERIALS AND METHODS: In a
      multistep participative design we identified key interests of adolescent patients
      with hypospadias. Next, a questionnaire addressing specifically the psychosexual
      satisfaction of adolescents after hypospadias repair was established. A
      population of 109 former patients with hypospadias was then assessed using this
      questionnaire. Furthermore, functional and cosmetic aspects, behavioural
      anomalies, and sexual activity were investigated. Age-matched patients undergoing
      circumcision served as control patients. Possible influence factors on patient
      satisfaction were investigated. Clinical trial registry site: German Registry of
      Clinical Trials DRKS, Freiburg, Germany (Reference: DRKS00003432). RESULTS: Key
      interests of adolescent patients were "normal appearance of the penis", "normal
      function of the penis regarding voiding and sexual activity", "no limitations
      regarding cosmetic appearance to others", "no limitations to sexual activity",
      and an "unimpaired masculine identity". The "Satisfaction In Genital Hypospadias
      Treatment" (SIGHT) questionnaire was developed using these items and using
      previously published evaluation systems. Nine questions address psychosexual
      aspects and two additional questions address current sexual activity. Internal
      consistency was high and retest reliability acceptable. The patient population
      showed a normal strength and difficulties score (SDQ). Overall satisfaction was
      high and similar to that of the control group. In a Spearman correlation a high
      SDQ value, erectile problems, and complications correlated negatively with
      satisfaction. CONCLUSION: To date, few studies have examined patients'
      satisfaction and psychosexuality. To our knowledge, the SIGHT questionnaire is
      the first to be developed participatively and in a stepwise fashion in
      collaboration with a paediatric psychologist and an open approach to determine
      items specifically important for adolescents. The SIGHT questionnaire can thus
      offer a relevant assessment of patients' psychosexual satisfaction. It is most
      suitable to supplement current strategies that so far mostly neglect the impact
      on psychosexual wellbeing.

PMID- 27889218
TI  - Single stage urethroplasty for perineal hypospadias in a horse: A case report.
AB  - INTRODUCTION: Within the veterinary world, data regarding the surgical management
      of hypospadias is lacking. Reports within equines have documented resective
      phallectomy procedures rather than urethral reconstruction. This case report
      documents the first ever urethroplasty for an equine hypospadias, performed by a
      consultant paediatric surgeon. The urethroplasty was achieved by applying the
      same surgical principles mastered from paediatric urology to a horse. The
      indication for surgery was contact dermatitis of the hind-leg, which impaired the
      thoroughbred foal's racing potential. OPERATION: A single stage urethroplasty was
      performed, during which the wide urethral plate was tubularised in two layers and
      the urethral meatus was successfully relocated distally to open upon the glans.
      The urethroplasty was covered with dartos fascia and the penile shaft skin and
      prepuce were reconstructed. Post-operatively, urine flowed cranially and the
      contact dermatitis resolved. Minor superficial wound dehiscence was observed
      which was managed conservatively and self-resolved. Follow-up at 3 years
      confirmed the horse continues to void from the re-sited meatus without
      complication and went on to have an illustrious career within horseracing.
      CONCLUSION: We have documented the first reconstructive urethroplasty for
      hypospadias within a horse, achieved by adopting the surgical techniques normally
      implemented within paediatric urology with good functionality.

PMID- 27889219
TI  - Join the discussion on Twitter!

PMID- 27889220
TI  - Editorial.

PMID- 27889222
TI  - Long-term follow-up of composite bladder augmentation incorporating stomach in a
      multi-institutional cohort of patients with cloacal exstrophy.
AB  - INTRODUCTION: Composite bladder augmentation, incorporating gastric and bowel
      segments, has the theoretical advantage of metabolic neutrality while potentially
      avoiding the morbidities of gastrocystoplasty, such as hematuria-dysuria
      syndrome. The most common indication for this operation is a paucity of bowel,
      such as in cloacal exstrophy. Despite several early descriptive studies of this
      technique, there are no reports, to date, of long-term follow-up in this
      population. OBJECTIVE: To describe the outcomes of composite bladder augmentation
      utilizing stomach in a cohort of cloacal exstrophy patients. MATERIALS AND
      METHODS: A retrospective review of cloacal exstrophy patients who underwent
      composite bladder augmentation from 1984 to 2006 at two institutions was
      performed. The incidence of mortality and morbidities related to augmentation was
      evaluated. RESULTS: Eleven patients with cloacal exstrophy underwent composite
      bladder augmentation. Median age at initial augmentation was 6.4 years
      (interquartile range (IQR) 4.4-9.1). Median follow-up was 13.2 years (IQR 11.2
      24.6). The Summary table describes the types of composite bladder augmentations.
      Of the three patients with pre-operative metabolic acidosis, two improved with
      composite bladder augmentation and one developed metabolic alkalosis. Three
      developed hematuria-dysuria syndrome: one improved with staged ileocystoplasty,
      and two had persistent symptoms successfully treated with H2 receptor blockers.
      Two of 11 developed symptomatic bladder stones. There were no reported bladder
      perforations, bladder malignancies, conversions to incontinent urinary
      diversions, or deaths. CONCLUSION: With long-term follow-up, very few patients
      developed metabolic acidosis/alkalosis after composite bladder augmentation. The
      composite bladder augmentation will continue to be used in patients with cloacal
      exstrophy, in order to minimize the impact on the pre-existing short gut in these
      patients.

PMID- 27889221
TI  - The Swedish infant high-grade reflux trial: Study presentation and vesicoureteral
      reflux outcome.
AB  - INTRODUCTION: High-grade vesicoureteral reflux (VUR) in infants is associated
      with congenital renal abnormalities, recurrent UTI, and bladder dysfunction.
      Endoscopic treatment (ET) is a well-established method in children with low to
      moderate reflux grades, but there is a lack of randomised controlled trials
      regarding the use of ET versus continuous antibiotic prophylaxis in infants with
      high-grade VUR. OBJECTIVE: This study aimed to determine whether high-grade VUR
      in infants can be treated with endoscopic injection and whether ET is superior to
      antibiotic prophylaxis in the treatment of VUR. MATERIALS AND METHODS: This
      prospective, randomised, controlled, multicentre, 1-year follow-up trial
      comprised 77 infants (55 boys, 22 girls) <8 months of age with VUR grade 4-5 (n =
      30/n = 47). Of the infants, 52 (68%) had bilateral VUR. Thirty-nine were
      randomised to antibiotic prophylaxis and 38 to ET (with prophylaxis until
      resolution). Voiding cystourethrogram, ultrasound, renal scintigraphy, and free
      voiding observation were performed at study entry and after 1 year to evaluate
      VUR grade, and renal and bladder function. RESULTS: VUR grade <=2 was seen in 22
      (59%) infants in the endoscopy group and eight (21%) in the prophylaxis group at
      follow-up (p = 0.0014). The success rate in the endoscopy group was 100% in
      unilateral grade 4, falling to 31% in bilateral grade 5 (p = 0.0094).
      Correspondingly, the results in the prophylaxis group were 40% in grade 4 down to
      0% in bilateral grade 5 (p = 0.037) (Table). Logistic regression analyses
      identified ET, VUR grade 4, unilaterality, and low residual urine at baseline as
      positive predictors of VUR down-grading to <=2 (area under ROC curve 0.88). In
      four patients with reflux resolution after one injection, dilating reflux
      recurred at the 1-year follow-up. One patient had a UTI possibly related to ET.
      In our material four patients required re-implantation, of whom one was
      obstructive after injection. DISCUSSION: The opportunity to offer even small
      infants with high-grade VUR an alternative, minimally invasive treatment option
      is a great advance in paediatric urology. In this high-risk group, bilateral VUR
      grade 5 stands out with its poor bladder function and low chance of resolution.
      The recurrence rate of dilating VUR after successful ET is consistent with
      previous studies. The limitations are the relatively small number of patients and
      the short follow-up. CONCLUSION: High-grade VUR in infants can be treated with
      injection therapy and the resolution rate is higher than that of prophylaxis
      treatment. The complication rate is low and VUR grade 4, unilaterality, and low
      residual urine are favourable for the resolution and down-grading of VUR.

PMID- 27889223
TI  - Laparoscopic pyeloplasty: Initial experience with 3D vision laparoscopy and
      articulating shears.
AB  - INTRODUCTION: Laparoscopic reconstructive surgery is associated with a steep
      learning curve related to the use of two-dimensional (2D) vision and rigid
      instruments. With the advent of robotic surgery, three-dimensional (3D) vision,
      and articulated instruments, this learning curve has been facilitated. We present
      a hybrid alternative to robotic surgery, using laparoscopy with 3D vision and
      articulated shears. OBJECTIVE: To compare outcomes of children undergoing
      pyeloplasty using 3D laparoscopy with articulated instruments with those
      undergoing the same surgery using standard laparoscopy with 2D vision and rigid
      instruments. STUDY DESIGN: Medical charts of 33 consecutive patients with
      ureteropelvic junction obstruction who underwent laparoscopic pyeloplasty by a
      single surgeon from 2006 to 2013 were reviewed in a retrospective manner. The
      current 3D cohort was compared with the previous 2D cohort. Data on age, weight,
      gender, side, operative time, dimension (2D = 19 patients, 3D = 8 patients),
      presence of a crossing vessel, length of hospital stay, and complication rate
      were compared between the two groups. Articulating shears were used for pelvotomy
      and spatulation of the ureter in the 3D group. Statistical tests included linear
      regression models and chi square tests for trends using STATA software. RESULTS:
      Operative time per case was decreased by an average of 48 min in the group
      undergoing 3D laparoscopic pyeloplasty compared with the group undergoing 2D
      laparoscopic pyeloplasty (p = 0.02) (Figure). Complication rate and length of
      hospital stay were not significantly affected by the use of 3D laparoscopy.
      DISCUSSION: These favorable results are in accordance with previous literature
      emphasizing the importance of 3D vision in faster and more precise execution of
      complex surgical maneuvers. The use of flexible instruments has also helped
      overcome the well-described delicate step of a dismembered pyeloplasty, namely
      the pelvotomy and ureteral spatulation. Limitations of this study are those
      inherent to the retrospective study design. CONCLUSION: The use of 3D vision
      endoscopy with articulating instruments blurs the distinction between current
      robotic-assisted and conventional laparoscopic technology, and provides a hybrid
      alternative deserving further attention.

PMID- 27889224
TI  - Fetal megacystis: A systematic review.
AB  - : Fetal megacystis is variably defined and understood. The literature on fetal
      megacystis was systematically reviewed, focusing on prenatal diagnosis,
      associations and outcomes. This yielded a total of 18 primary references and
      eight secondary references. Fetal megacystis has an estimated first-trimester
      prevalence of between 1:330 and 1:1670, with a male to female ratio of 8:1. In
      the first trimester, megacystis is most commonly defined as a longitudinal
      bladder dimension of >=7 mm. Later in pregnancy, a sagittal dimension (in mm)
      greater than gestational age (in weeks) + 12 is often accepted. Megacystis can be
      associated with a thickened bladder wall, which has been objectively defined as
      >3 mm. Oligohydramnios is present in approximately half of all cases. The most
      common underlying diagnosis is posterior urethral valves (57%), followed by
      urethral atresia/stenosis (7%), prune belly syndrome (4%), megacystis-microcolon
      intestinal-hypoperistalsis syndrome (MMIHS) (1%), and cloacal anomalies (0.7%).
      Karyotype anomalies are found in 15%, and include trisomy 18, trisomy 13 and
      trisomy 21. Ultrasound imaging alone is often insufficient to enable a definitive
      diagnosis, although it may indicate that a specific diagnosis is more likely.
      Overall, about 50% of reported fetuses with megacystis are terminated, but this
      proportion varies considerably between countries and over time. Prognostic
      stratification is evolving, with the most important factors being
      oligohydramnios, gestational age at diagnosis, degree of bladder enlargement,
      renal hyperechogenicity, karyotype, and sex. CONCLUSIONS: This review
      demonstrated some consensus on the ultrasound criteria for defining fetal
      megacystis, and illustrated the spectrum of pathologies and their relative
      frequencies that can cause this condition. It also underlined important
      associated karyotype anomalies. To progress understanding of the natural history
      of enlarged fetal bladders, more accurate diagnostics are required, and risk
      stratification needs to be refined to facilitate prenatal counseling.

PMID- 27889226
TI  - Editorial: Toxins 2017.

PMID- 27889225
TI  - Cost-estimate and proposal for a development impact bond for canine rabies
      elimination by mass vaccination in Chad.
AB  - Close to 69,000 humans die of rabies each year, most of them in Africa and Asia.
      Clinical rabies can be prevented by post-exposure prophylaxis (PEP). However, PEP
      is commonly not available or not affordable in developing countries. Another
      strategy besides treating exposed humans is the vaccination of vector species. In
      developing countries, the main vector is the domestic dog, that, once infected,
      is a serious threat to humans. After a successful mass vaccination of 70% of the
      dogs in N'Djamena, we report here a cost-estimate for a national rabies
      elimination campaign for Chad. In a cross-sectional survey in four rural zones,
      we established the canine : human ratio at the household level. Based on human
      census data and the prevailing socio-cultural composition of rural zones of Chad,
      the total canine population was estimated at 1,205,361 dogs (95% Confidence
      interval 1,128,008-1,736,774 dogs). Cost data were collected from government
      sources and the recent canine mass vaccination campaign in N'Djamena. A Monte
      Carlo simulation was used for the simulation of the average cost and its
      variability, using probability distributions for dog numbers and cost items.
      Assuming the vaccination of 100 dogs on average per vaccination post and a
      duration of one year, the total cost for the vaccination of the national Chadian
      canine population is estimated at 2,716,359 Euros (95% CI 2,417,353-3,035,081)
      for one vaccination round. A development impact bond (DIB) organizational
      structure and cash flow scenario were then developed for the elimination of
      canine rabies in Chad. Cumulative discounted cost of 28.3 million Euros over ten
      years would be shared between the government of Chad, private investors and
      institutional donors as outcome funders. In this way, the risk of the investment
      could be shared and the necessary investment could be made available upfront - a
      key element for the elimination of canine rabies in Chad.

PMID- 27889228
TI  - Cardioprotective effect of Vitex negundo on isoproterenol-induced myocardial
      necrosis in wistar rats: A dual approach study.
AB  - Cardiovascular diseases (CVDs) are becoming the major cause of deaths worldwide,
      and their treatment demands novel therapeutic strategies. In this connection, we
      have identified p21 activated kinase 1 (PAK1) as a novel therapeutic target for
      the treatment of myocardial infarction (MI), where its expression is decreased
      when MI is induced with isoproterenol (ISO), which was brought back normal with
      pretreatment of Vitex negundo leaf ethanolic extract (VNE). These results were
      also supported by histopathological studies, cardiac markers, antioxidants, and
      inflammatory cytokines (NF-kappaB and IL-1beta). Further studies with GC-MS
      analysis of VNE and in silico experiments confirmed 5,7-dihydroxy-6,4',-dimethoxy
      flavonone and 3',5-dihydroxy-6,7,4',-trimethoxyflavone are responsible for either
      maintaining or inducing the expression of PAK1 to protect from MI. Our findings
      for the first time revealed the use of phytoconstituents in the treatment of MI.

PMID- 27889229
TI  - Brown propolis attenuates cerebral ischemia-induced oxidative damage via
      affecting antioxidant enzyme system in mice.
AB  - Oxidative stress plays a critical role in ischemic brain injury. Superoxide
      dismutase (SOD) and glutathione peroxidase (GPx) are the enzymes underlying the
      endogenous antioxidant mechanisms affected by stroke and are considered as
      oxidative stress biomarkers. Brown propolis (BP) is a bioactive natural product
      with a set of biological activities that in turn may differ depending on the area
      from which the substance is originated. The aim of this study was to investigate
      the effect of water-extracted brown propolis (WEBPs), from two regions of Iran,
      against cerebral ischemia-induced oxidative injury in a mouse model of stroke.
      Experimentally, the chemical characterization and total polyphenol content were
      determined using GC/MS and Folin-Ciocalteu assay respectively. Seventy-two adult
      male mice were randomly divided into the surgical sham group, control group
      (treated with vehicle), and four groups of WEBPs-treated animals. The WEBPs were
      administered at the doses of 100 and 200mg/kg IP, during four different time
      points. Oxidative stress biomarkers (SOD and GPx activity, SOD/GPx ratio), lipid
      peroxidation (LPO) index (malondialdehyde content) and infarct volume were
      measured 48h post stroke. Behavioral tests were evaluated 24 and 48h after
      stroke. WEBPs treatment resulted in significant restoration of antioxidant
      enzymes activity and a subsequent decrease in LPO as well as the infarct volume
      compared to the control group. Sensory-motor impairment and neurological deficits
      were improved significantly as well. These results indicate that Iranian BP
      confers neuroprotection on the stroke-induced neuronal damage via an antioxidant
      mechanism which seems to be mediated by the endogenous antioxidant system.

PMID- 27889227
TI  - GPCR Signaling and Trafficking: The Long and Short of It.
AB  - Emerging findings disclose unexpected components of G protein-coupled receptor
      (GPCR) signaling and cell biology. Select GPCRs exhibit classical signaling, that
      is restricted to cell membranes, as well as newly described persistent signaling
      that depends on internalization of the GPCR bound to beta-arrestins. Termination
      of non-canonical endosomal signaling requires intraluminal acidification and
      sophisticated protein trafficking machineries. Recent studies reveal the
      structural determinants of the trafficking chaperones. This review summarizes
      advances in GPCR signaling and trafficking with a focus on the parathyroid
      hormone receptor (PTHR) as a prototype, and on the actin-sorting nexin 27 (SNX27)
      retromer tubule (ASRT) complex, an endosomal sorting hub responsible for
      recycling and preservation of cell surface receptors. The findings are integrated
      into a model of PTHR trafficking with implications for signal transduction, bone
      growth, and mineral ion metabolism.

PMID- 27889230
TI  - Anticancer effects of novel thalidomide analogs in A549 cells through inhibition
      of vascular endothelial growth factor and matrix metalloproteinase-2.
AB  - Lung cancer is one of the major causes of cancer-related mortality worldwide, and
      non-small-cell lung cancer is the most common form of lung cancer. Several
      studies had shown that thalidomide has potential for prevention and therapy of
      cancer. Therefore, the current study aimed to investigate the antitumor effects
      of two novel thalidomide analogs in human lung cancer A549 cells. The
      antiproliferative, antimigratory, and apoptotic effects in A549 cells induced by
      thalidomide analogs were examined. In addition, their effects on the expression
      of mRNAs encoding vascular endothelial growth factor165 (VEGF165) and matrix
      metalloproteinase-2 (MMP-2) were evaluated. Their influence on the tumor volume
      in nude mice was also determined. Results revealed that thalidomide analogs
      exhibited antiproliferative, antimigratory, and apoptotic activities with more
      pronounced effect than thalidomide drug. Furthermore, analogs 1 and 2 suppressed
      the expression levels of VEGF165 by 42% and 53.2% and those of MMP-2 by 45% and
      52%, respectively. Thalidomide analogs 1 and 2 also reduced the tumor volume by
      30.11% and 53.52%, respectively. Therefore, this study provides evidence that
      thalidomide analogs may serve as a new therapeutic option for treating lung
      cancer.

PMID- 27889231
TI  - Nimbolide inhibits androgen independent prostate cancer cells survival and
      proliferation by modulating multiple pro-survival signaling pathways.
AB  - BACKGROUND: Prostate cancer is the most prominent cancer in men, experiencing a
      relapse in disease often express high serum TNF-alpha levels. It has been
      correlated with increased cell survival and proliferation of prostate cancer
      cells. Previous studies reported that nimbolide, a terpenoid derived from the
      leaves and flowers of neem tree inhibits cancer growth through selective
      modulation of cell signaling pathways linked to inflammation, survival,
      proliferation, angiogenesis and metastasis. METHODS: The present study aimed to
      examine the effect of nimbolide at 1 and 2MUM concentrations on TNF-alpha/TNFR1
      mediated signaling molecules involved in cell survival and proliferation in PC-3
      cell line via NF-kappaB and MAPK pathways by real time PCR and western blot.
      Protein and compound interaction were performed by Molecular docking analysis.
      RESULTS: Our results indicate that nimbolide treatment suppressed expression of
      TNF-alpha, SODD, Grb2, SOS mRNA and modulated TNF-alpha/TNFR1 regulated NF-kappaB
      and MAPK signaling molecules in PC-3 cells. Additional molecular dynamics
      simulation studies confirmed the stability of nimbolide and signaling molecules
      binding interactions. Binding pose analysis revealed the significance of hydrogen
      bond interactions for effective stabilization of virtual ligand protein
      complexes. CONCLUSION: Nimbolide inhibited prostate cancer cell survival and
      proliferation via NF-kappaB and MAPK pathways.

PMID- 27889232
TI  - l-Methionine and silymarin: A comparison of prophylactic protective capabilities
      in acetaminophen-induced injuries of the liver, kidney and cerebral cortex.
AB  - We compared the relative protective abilities of silymarin and l-methionine pre
      treatment in acetaminophen overdose injuries of the liver, kidney and cerebral
      cortex by assessing behaviours, antioxidant status, tissue histological changes
      and biochemical parameters of hepatic/renal function. Rats were divided into six
      groups of ten each; animals in five of these groups were pre-treated with oral
      distilled water, silymarin (25mg/kg) or l-methionine (2.5, 5 and 10mg/kg body
      weight) for 14days; and then administered intraperitoneal (i.p.) acetaminophen at
      800mg/kg/day for 3days. Rats in the sixth group (normal control) received
      distilled water orally for 14days and then i.p. for 3days. Neurobehavioural tests
      were conducted 7days after last i.p treatment, and animals sacrificed on the 8th
      day. Plasma was assayed for biochemical markers of liver/kidney function; while
      sections of the liver, kidney and cerebral cortex were either homogenised for
      assay of antioxidant status or processed for histology. Acetaminophen overdose
      resulted in locomotor retardation, excessive self-grooming, working-memory
      impairment, anxiety, derangement of liver/kidney biochemistry, antioxidant
      imbalance, and histological changes in the liver, kidney and cerebral cortex.
      Administration of silymarin or increasing doses of l-methionine counteracted the
      behavioural changes, reversed biochemical indices of liver/kidney injury, and
      improved antioxidant activity. Silymarin and l-methionine also conferred variable
      degrees of tissue protection, on histology. Either silymarin or l-methionine can
      protect vulnerable tissues from acetaminophen overdose injury; however, each
      offers variable protection to different tissues. This study highlights an
      obstacle to seeking the 'ideal' protective agent against acetaminophen overdose.

PMID- 27889235
TI  - Prevalence and topographic distribution of spinal inflammation on MR imaging in
      patients recently diagnosed with axial spondyloarthritis.
AB  - OBJECTIVE: The primary goal of this study was to determine the prevalence and
      topographic distribution of spinal lesions in lower thoracic and lumbar spine on
      magnetic resonance imaging (MRI) in patients with recently diagnosed with
      spondyloarthritis. The secondary goal was to identify variables associated with
      vertebral patterns consistent with spondyloarthritis on MRI. PATIENTS AND
      METHODS: A total of 112 HLA-B27 positive patients with recently diagnosed
      spondyloarthritis were retrospectively included. There were 70 women and 42 men,
      with a mean age of 41 years+/-12 (SD) (range: 17-70years). Mean symptom duration
      was 1year (range: 0-7years). MRI examinations of sacroiliac joints and
      thoracolumbar spine were reviewed for the presence of bone marrow edema, chronic
      structural abnormalities, and vertebral patterns consistent with
      spondyloarthritis. Age, gender and disease duration of patients with vertebral
      patterns on MRI consistent with spondyloarthritis were compared with those
      without MRI signs of spondyloarthritis. RESULTS: Thirty-six patients (32.1%)
      showed spinal patterns of spondyloarthritis, including 16 patients (14.3%) with
      no associated inflammatory sacroiliitis. Posterior inflammatory lesions were
      present in 20.5% of patients. Posterior spinal inflammatory lesions were
      significantly associated with vertebral corner inflammatory lesions (P=0.03).
      There were no differences in age, sex or mean duration of symptoms between the
      two groups of patients. CONCLUSION: Spinal involvement is observed in 32.1% of
      HLA-B27 positive patients with recently diagnosed spondyloarthritis and is not
      associated with sacroiliitis in 14.3%. Age, gender or symptom duration are not
      associated with spinal involvement on MRI.

PMID- 27889234
TI  - In-silico and in-vitro anti-cancer potential of a curcumin analogue (1E, 6E)-1, 7
      di (1H-indol-3-yl) hepta-1, 6-diene-3, 5-dione.
AB  - PURPOSE: Previously we showed that BDMC, an analogue of curcumin suppresses
      growth of human breast and laryngeal cancer cell line by causing apoptosis. Here,
      we demonstrate the enhanced anti-cancer activity of a heterocyclic ring (indole)
      incorporated curcumin analogue ((1E, 6E)-1, 7-di (1H-indol-3-yl) hepta-1, 6-diene
      3, 5-Dione), ICA in short, in comparison to curcumin. METHOD: ICA was synthesized
      by a one pot condensation reaction. Anti-cancer potential of ICA was assessed in
      three human cancer cell lines of different origin (Lung adenocarcinoma (A549),
      leukemia (K562) and colon cancer (SW480)) by MTT assay. Mode of cell death was
      determined by acridine orange-ethidium bromide (Ao-Eb) staining. Putative
      cellular targets of ICA were investigated by molecular docking studies. Cell
      cycle analysis following curcumin or ICA treatment in SW480 cell line was carried
      out by flow cytometry. Expression levels of Cyclin D1 and apoptotic markers, such
      as Caspase 3, 8 and 9 were studied by western blot analysis in SW480 cell line
      treated with or without ICA and curcumin. RESULTS: The yield of ICA synthesis was
      found to be 69% with a purity of 98%. ICA demonstrated promising anti-cancer
      activity compared to curcumin alone, as discerned by MTT assay. ICA was non-toxic
      to the cell line of normal origin. We further observed that ICA is ~2 fold more
      potent than curcumin in inhibiting the growth of SW480 cells. Ao-Eb staining
      revealed that ICA could induce apoptosis in all the cell lines tested. Molecular
      docking studies suggest that ICA may possibly exhibit its anticancer effect by
      inhibiting EGFR in A549, Bcr-Abl in K562 and GSK-3beta kinase in SW480 cell line.
      Moreover, ICA showed strong binding avidity for Bcl-2 protein in silico, which
      could result in induction of apoptosis. Cell cycle analysis revealed that both
      curcumin and ICA induced concomitant cell cycle arrest at G0/G1 and G2/M phase.
      Western blot shows that ICA could effectively down regulate the expression of
      cell cycle protein cyclin D1, while promoting the activation of Caspase 3, 8 and
      9 when compared to curcumin in human colon cancer cell line SW480. CONCLUSION:
      The result of this study indicates that ICA could hold promise to be a potential
      anti-cancer agent. Since ICA has shown encouraging results in terms of its anti
      cancer activity compared to curcumin, further research is necessary to fully
      delineate the underlying molecular mechanism of its anticancer potential.

PMID- 27889233
TI  - Icaritin induces mitochondrial apoptosis by up-regulating miR-124 in human oral
      squamous cell carcinoma cells.
AB  - AIM OF THE STUDY: The present study is aimed to investigate the apoptosis
      inducing effect of icaritin in human oral squamous cell carcinoma (OSCC) cells
      and the associated mechanisms. MATERIALS AND METHODS: KB and SCC9 cell lines were
      used as model cell lines. Effect of icaritin on apoptosis was analyzed by flow
      cytometry. The effect of icaritin on mitochondrial apoptotic pathway was
      demonstrated by loss of mitochondrial membrane potential and release of cytocrome
      C from mitochondria. MiR-124 mimic and miR-124 inhibitor were used to manipulate
      the expression of miR-124 in OSCC cells. SiRNA targeting Sp1 and DNMT1 as well as
      Sp1 and DNMT1 overexpressing vector were utilized to confirm their roles in the
      apoptosis-inducing effect of icaritin in OSCC cells. Activation of relevant
      signaling pathway by icaritin and effect of icaritin on expression of targeting
      molecules were determined by western blots or qRT-PCR. RESULTS: Our results
      showed that icaritin inhibited tumor cell viability in a dose- and time-dependent
      manner, and induced cell apoptosis via intrinsic mitochondrial pathway by
      upregulating miR-124. Moreover, our results showed that the icaritin exerted
      regulatory effect on miR-124 through suppressing Sp1/DNMT1 signaling. CONCLUSION:
      Our data provide the first experimental evidence that icaritin induces
      mitochondrial apoptosis in OSCC cells by upregulating miR-124 and suggest a new
      mechanism to explain its anti-tumor effects.

PMID- 27889236
TI  - Pacemakers and MRI: A protocol in line with international guidelines and approved
      by the SFICV (French Society of Cardiovascular Imaging).

PMID- 27889237
TI  - Universal prevention of eating disorders: A concept analysis.
AB  - The definition of universal prevention is important for theoretical, research,
      and policy-related reasons. The present article provides an etymological and
      historical look at the concept of universal prevention, in and of itself and in
      terms of its position on the mental health intervention spectrum involving mental
      health promotion, selective prevention, indicated prevention, case
      identification, and treatment. Following a summary of the features commonly
      associated with universal prevention, these characteristics are fashioned into a
      family resemblance model for defining the construct. This model is applied to
      four of the articles constituting the journal Eating Behaviors' special issue on
      the universal prevention of eating disorders. It is argued that this family
      resemblance approach captures the diversity of current universal approaches to
      reducing risk factors and/or preventing eating disorders. This type of
      definition, coupled with Foxcroft's (2014) tripartite functional analysis of
      universal prevention, has the potential to improve evaluations of universal
      prevention, as well as large-scale collaborative projects that seek to integrate
      programs across the mental health intervention spectrum.

PMID- 27889240
TI  - A balanced motor primitive framework can simultaneously explain motor learning in
      unimanual and bimanual movements.
AB  - Certain theoretical frameworks have successfully explained motor learning in
      either unimanual or bimanual movements. However, no single theoretical framework
      can comprehensively explain motor learning in both types of movement because the
      relationship between these two types of movement remains unclear. Although our
      recent model of a balanced motor primitive framework attempted to simultaneously
      explain motor learning in unimanual and bimanual movements, this model focused
      only on a limited subset of bimanual movements and therefore did not elucidate
      the relationships between unimanual movements and various bimanual movements.
      Here, we extend the balanced motor primitive framework to simultaneously explain
      motor learning in unimanual and various bimanual movements as well as the
      transfer of learning effects between unimanual and various bimanual movements;
      these phenomena can be simultaneously explained if the mean activity of each
      primitive for various unimanual movements is balanced with the corresponding mean
      activity for various bimanual movements. Using this balanced condition, we can
      reproduce the results of prior behavioral and neurophysiological experiments.
      Furthermore, we demonstrate that the balanced condition can be implemented in a
      simple neural network model.

PMID- 27889238
TI  - Insights into Nucleosome Organization in Mouse Embryonic Stem Cells through
      Chemical Mapping.
AB  - Nucleosome organization influences gene activity by controlling DNA accessibility
      to transcription machinery. Here, we develop a chemical biology approach to
      determine mammalian nucleosome positions genome-wide. We uncovered surprising
      features of nucleosome organization in mouse embryonic stem cells. In contrast to
      the prevailing model, we observe that for nearly all mouse genes, a class of
      fragile nucleosomes occupies previously designated nucleosome-depleted regions
      around transcription start sites and transcription termination sites. We show
      that nucleosomes occupy DNA targets for a subset of DNA-binding proteins,
      including CCCTC-binding factor (CTCF) and pluripotency factors. Furthermore, we
      provide evidence that promoter-proximal nucleosomes, with the +1 nucleosome in
      particular, contribute to the pausing of RNA polymerase II. Lastly, we find a
      characteristic preference for nucleosomes at exon-intron junctions. Taken
      together, we establish an accurate method for defining the nucleosome landscape
      and provide a valuable resource for studying nucleosome-mediated gene regulation
      in mammalian cells.

PMID- 27889239
TI  - Structural Mechanism for Cargo Recognition by the Retromer Complex.
AB  - Retromer is a multi-protein complex that recycles transmembrane cargo from
      endosomes to the trans-Golgi network and the plasma membrane. Defects in retromer
      impair various cellular processes and underlie some forms of Alzheimer's disease
      and Parkinson's disease. Although retromer was discovered over 15 years ago, the
      mechanisms for cargo recognition and recruitment to endosomes have remained
      elusive. Here, we present an X-ray crystallographic analysis of a four-component
      complex comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin
      SNX3, and a recycling signal from the divalent cation transporter DMT1-II. This
      analysis identifies a binding site for canonical recycling signals at the
      interface between VPS26 and SNX3. In addition, the structure highlights a network
      of cooperative interactions among the VPS subunits, SNX3, and cargo that couple
      signal-recognition to membrane recruitment.

PMID- 27889241
TI  - Natural and Synthetic Coral Biomineralization for Human Bone Revitalization.
AB  - Coral skeletons can regenerate replacement human bone in nonload-bearing
      excavated skeletal locations. A combination of multiscale, interconnected pores
      and channels and highly bioactive surface chemistry has established corals as an
      important alternative to using healthy host bone replacements. Here, we highlight
      how coral skeletal systems are being remolded into new calcified structures or
      synthetic corals by biomimetic processes, as places for the organized permeation
      of bone tissue cells and blood vessels. Progressive technologies in coral
      aquaculture and self-organization inorganic chemistry are helping to modify
      natural corals and create synthetic coral architectures able to accelerate bone
      regeneration with proper host integration at more skeletal locations, adapted to
      recent surgical techniques and used to treat intrinsic skeletal deformities and
      metabolic conditions.

PMID- 27889242
TI  - Benign mesial temporal lobe epilepsy: A clinical cohort and literature review.
AB  - OBJECTIVE: We present a single-center retrospective study of benign mesial
      temporal lobe epilepsy (bMTLE) between 1995 and 2014. METHODS: Hospital records
      and clinic charts were reviewed. The clinical, Eelectroencephalographic (EEG),
      imaging features, and response to treatment with antiepileptic drugs (AEDs) were
      documented. Patients were included in this study if they were seizure-free for a
      minimum of 24months with or without an AED. RESULTS: Twenty-seven patients were
      identified. There were 19 (70%) females, mean age at first seizure was 32.2
      (range: 15-80years). In all patients, seizures were mild, and seizure freedom was
      readily achieved with the initiation of AED therapy. Sixteen patients (59%) had
      mesial temporal sclerosis (MTS). In three patients, we attempted to discontinue
      AED therapy after a prolonged period of remission (5-8years), but all had seizure
      recurrence within 2 to 4weeks. SIGNIFICANCE: Not all temporal lobe epilepsy is
      refractory to medication, despite the presence of MTS. Until clinical trials
      indicate otherwise, surgery is not indicated but life-long medical treatment is
      advocated.

PMID- 27889243
TI  - Antiprotozoal and antioxidant alkaloids from Alternanthera littoralis.
AB  - Five alkaloids, in addition to hydroxytyrosol and uridine, were isolated from
      aerial parts of Alternanthera littoralis P. Beauv. Among the isolated compounds,
      alternamide A was an unusual tricyclic alkaloid with a bridged benzoazepine core.
      All isolated alkaloids have a catechol moiety, indicating a possible common
      biosynthetic route. Their structures were established by 1D and 2D NMR
      spectroscopy in combination with extensive tandem MS experiments by collisional
      induced dissociation (CID). The antiprotozoal activity of the isolated compounds
      was assayed against trypomastigote forms of Trypanosoma cruzi and amastigotes of
      Leishmania amazonensis. Alternamine A was the most active compound, reducing
      markedly the viability of both parasites. Antioxidant capacities evaluated by
      ORACFL assay showed that the isolated alkaloids (mainly alternamide B)
      contributed to the high activity recorded for the ethanolic crude extract;
      possibly, the catechol moiety present in all structures plays a central role in
      this result.

PMID- 27889244
TI  - Medicinal uses, chemistry and pharmacology of Dillenia species (Dilleniaceae).
AB  - The genus Dillenia is comprised of about 100 species of evergreen and deciduous
      trees or shrubs of disjunct distribution in the seasonal tropics of Madagascar
      through South and South East Asia, Malaysia, North Australia, and Fiji. Species
      from this genus have been widely used in medicinal folklore to treat cancers,
      wounds, jaundice, fever, cough, diabetes mellitus, and diarrhea as well as hair
      tonics. The plants of the genus also produce edible fruits and are cultivated as
      ornamental plants. Flavonoids, triterpenoids, and miscellaneous compounds have
      been identified in the genus. Their extracts and pure compounds have been
      reported for their antimicrobial, anti-inflammatory, cytotoxic, antidiabetes,
      antioxidant, antidiarrheal, and antiprotozoal activities. Mucilage from their
      fruits is used in drug formulations.

PMID- 27889245
TI  - Selagintriflavonoids with BACE1 inhibitory activity from the fern Selaginella
      doederleinii.
AB  - Eight triflavonoids, selagintriflavonoids A-H, were isolated from whole herbs of
      Selaginella doederleinii. The structures of compounds selagintriflavonoids A-C
      consisted of three naringenin units, whereas those of selagintriflavonoids D-H
      consisted of apigenin and two naringenin moieties. The structures and absolute
      configurations of the compounds were determined based on NMR, HRESIMS, and
      experimental and calculated electronic circular dichroism (ECD) data. The ability
      of the compounds to inhibit beta-secretase (BACE1) was also evaluated. All
      compounds exhibited BACE1 inhibition with IC50 values ranging from 0.75 to 46.99
      MUM. Selagintriflavonoid A exhibited the strongest inhibition (0.75 MUM) and is
      thus a promising compound for treating Alzheimer's disease.

PMID- 27889246
TI  - Risk factors for Propionibacterium acnes infection after neurosurgery: A case
      control study.
AB  - Propionibacterium acnes is increasingly known as a causative organism for post
      neurosurgical infection; however, no clinical studies have examined the risk
      factors associated with P. acnes infections. Clinical data obtained from 14 cases
      of P. acnes infection and 28 controls infected with other pathogens were
      analyzed. Craniotomy, malignancy, and prolonged duration of operation were
      significantly associated with the onset of P. acnes infection. No fatal cases
      were reported.

PMID- 27889247
TI  - Cutaneous invasive aspergillosis in a patient with glioblastoma receiving long
      term temozolomide and corticosteroid therapy.
AB  - Glioblastoma is an aggressive brain tumor that requires multidisciplinary
      treatment including adjuvant radiotherapy, chemotherapy, and adjunct
      corticosteroids. Temozolomide is a commonly used chemotherapy drug and frequently
      causes lymphocytopenia. We describe the case of a 67-year-old woman with
      cutaneous invasive aspergillosis who had received long-term temozolomide and
      corticosteroid therapy for glioblastoma. She presented with multiple indurations,
      erythema, and purpura, some of which produced purulent discharge, in the anterior
      abdomen. Extensive intra- or inter-muscular abscesses of the right anterior
      abdominal wall were also observed. Her absolute lymphocyte counts were 156/MUL on
      admission. Cultures obtained from the wound yielded Aspergillus fumigatus. She
      was diagnosed with secondary cutaneous invasive aspergillosis, which likely
      resulted from hematogenous dissemination. Although rare, this case illustrates
      that temozolomide-induced lymphocytopenia, especially in cases of concomitant
      corticosteroid use, can be associated with severe invasive aspergillosis.

PMID- 27889248
TI  - Comprehensive study to investigate the role of various aminoglycoside resistance
      mechanisms in clinical isolates of Acinetobacter baumannii.
AB  - Therapeutic resistance towards most of the current treatment regime by
      Acinetobacter baumannii has reduced the prescribing antibiotic pattern and option
      is being re-shifted towards more toxic agents including aminoglycosides. The
      present investigation aimed at to study various mechanisms towards aminoglycoside
      non-susceptibility in clinical isolates of A. baumannii. The bacteria were
      subjected to genetic basis assessment for the presence of aminoglycoside
      modifying enzymes (AME), 16S rRNA methylase encoding genes and relative
      expression of AdeABC and AbeM efflux pumps in relation to their susceptibility to
      five aminoglycosides. When isolates were subjected to typing by repetitive
      extragenic palindromic (REP) PCR, isolates could be separated into thirteen
      definite clones. The majority of isolates (94%) were positive for AME encoding
      genes. Possession of ant(2')-Ia correlated with non-susceptibility towards
      gentamicin, amikacin, kanamycin, tobramycin; while, presence of aph(3')-VIa
      attributed to resistance towards amikacin, kanamycin; possession of aac(3')-Ia
      allied with non-susceptibility to amikacin, tobramycin and presence of aac(3')IIa
      correlated with kanamycin non-susceptibility. Presence of armA was detected in
      34.4%, 34.2%, 29.2%, 40.3%, and 64.2% of isolates showing non-susceptibility to
      gentamicin, amikacin, kanamycin, tobramycin and netilmicin, respectively. No
      isolates were found to carry rmtB or rmtC. Amikacin non-susceptibility in
      comparison to other aminoglycosides correlated with over production of adeB.
      Overall, the results represented a definitive correlation between presence of AME
      encoding genes as well as armA and resistance of A. baumannii towards
      aminoglycosides. On the other hand, the up-regulation of AdeABC and AbeM systems
      was found to have only the partial role in development of aminoglycoside
      resistance.

PMID- 27889249
TI  - Analysis of Streptococcus pneumoniae and Haemophilus influenzae isolated from
      middle ear fluid before and after the introduction of government subsidies for
      pneumococcal and H. influenzae type b vaccines in Japan.
AB  - This study aimed to identify trends in frequency, serotype, and antimicrobial
      susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolated
      from middle ear fluid specimens of children aged<=15 years (mean, 2 years),
      before and after the introduction of the 7-valent pneumococcal conjugate vaccine
      (PCV7) and the H. influenzae type b vaccine, at a pediatric facility in Japan.
      Sixty-six S. pneumoniae and 88 H. influenzae strains were isolated from 820
      middle ear fluid samples. Serotyping and antimicrobial susceptibility testing
      were performed. The study time-frame was divided into period 1 (2007-2010) and
      period 2 (2011-2014), according to the availability of vaccine public funding.
      The S. pneumoniae detection rate decreased from 9.6% in period 1-6.1% in period 2
      (p = 0.042). PCV7 serotypes decreased from 56.8% to 9.1% (p = 0.0002). No
      significant change was observed for the 13-valent pneumococcal conjugate vaccine
      (PCV13) serotypes: 72.7% in period 1 and 59.1% in period 2. Penicillin-resistant
      strains (penicillin G-MIC >=2 MUg/mL) decreased from 25% to 4.5% (p = 0.038).
      Detection rates for H. influenzae did not change significantly: 10.3% in period 1
      and 11.3% in period 2. Serotypes were mostly non-typeable: 97.9% in period 1 and
      90.2% in period 2, and only one serotype b strain was isolated in each period.
      The frequency of ampicillin-resistant strains (MIC >=4 MUg/mL) did not change.
      These results show a preventative effect of PCV7 on otitis media due to S.
      pneumoniae. PCV7 was replaced with PCV13 in 2013 in Japan; therefore, a further
      decrease in pneumococcal otitis media is anticipated in the future.

PMID- 27889250
TI  - Positive end-expiratory pressure does not decrease cardiac output during
      laparoscopic liver surgery: A prospective observational evaluation.
AB  - BACKGROUND: Positive end-expiratory pressure (PEEP) has beneficial pulmonary
      effects but may worsen the hemodynamic repercussions induced by pneumoperitoneum
      (PNP) in patients undergoing laparoscopic liver resection. However, by increasing
      intraluminal vena cava (VC) pressures, PEEP may prevent PNP-induced VC collapse.
      The aim of this study was to test the validity of this hypothesis. METHODS: After
      IRB approval and written informed consent, 20 patients were evaluated
      prospectively. Measurements were performed before and after the application of 10
      cmH2O PEEP on patients without PNP (Control group) and during a 12 cmH20 PNP.
      Results are provided as means [95%CI]. Comparison used paired-sample t test.
      RESULTS: PEEP induced a decrease in CI in Control subgroup (2.3 [2.0-2.6] and 2.1
      [1.8-2.4] l min-1 m-2 before and after PEEP. P < 0.05). In contrast, PEEP on a
      pre-established PNP did not significantly modify cardiac index (CI). Transmural
      pressure on the abdominal vena cava decreased with PNP but was partly reversed by
      the addition of PEEP. CONCLUSION: The application of PEEP on a pre-established
      PNP during laparoscopic liver resection in normovolemic patients did not decrease
      CI. Analysis of transmural VC pressure variations confirms that the addition of
      PEEP may prevent the vena caval collapse induced by PNP.

PMID- 27889251
TI  - Modified protocol for drug susceptibility testing of MGIT cultures of
      Mycobacterium tuberculosis by the MGIT 960.
AB  - A rapid detection of resistance in Mycobacterium tuberculosis is crucial for
      management and control of tuberculosis. This study evaluated a more rapid and
      cost-effective drug susceptibility testing (DST) protocol using primary isolates
      of M. tuberculosis in mycobacteria growth indicator tube (MGIT). Ninety-four M.
      tuberculosis isolates in MGIT were subjected to DST by the manufacturer's method,
      i.e., primary isolates were subcultured and DST was performed from positive
      cultures for a maximum of 5days; and by our modified method, i.e., DST was
      performed directly from primary MGIT cultures positive for more than 5days.
      Results were concordant for 76 (81%) isolates. Agreement between both methods was
      92.0%, 98.9%, 97.7%, and 95.5% for streptomycin, isoniazid, rifampicin, and
      ethambutol, respectively. Six isolates failed to grow on the recommended method,
      including 3 resistant isolates. Not performing subculture of primary M.
      tuberculosis isolates yields reliable results, decreasing the turnaround time and
      the cost of the test.

PMID- 27889252
TI  - Peripartum maternal transmission of extended-spectrum beta-lactamase organism to
      newborn infants.
AB  - The aim of this study was to determine whether the route of extended-spectrum
      beta-lactamase (ESBL) transmission to hospitalized newborns was from their
      mothers during delivery. Neonatal intensive care unit (NICU) hospitalized
      newborns were sampled for ESBL presence by stool cultures on the first and fourth
      days of life. Mothers of ESBL-positive newborns were sampled for possible
      correlation detection. Bacteria isolates were molecularly identified and
      susceptibility tests for antibiotic agents were performed. Of the 225 newborns,
      14 (6.2%) were ESBL positive, 10 (4.4%) were Escherichia coli positive, and 4
      (1.7%) were Klebsiella pneumoniae positive. Among the 14 mothers of positive
      newborns, 13 (92.8%) were found ESBL positive and one mother of a newborn with E.
      coli carriage was found ESBL negative. Genes encoding for ESBL resistance were
      identified. Antibiotic sensitivity and resistance were tested. This study
      demonstrated that ESBL bacteria carrier neonates hospitalized in NICU may be a
      result of transmission from mother to baby during delivery.

PMID- 27889253
TI  - Blood and tissue distribution of posaconazole in a rat model of invasive
      pulmonary aspergillosis.
AB  - Posaconazole is the recommended prophylactic agent in patients at high risk of
      invasive fungal infection, since adequate drug levels seem to be reached in
      target sites despite the relatively low levels detected in blood. The objective
      of this study is to obtain pharmacokinetic (PK) information associated to blood
      and tissue distribution of posaconazole in an animal model of invasive pulmonary
      aspergillosis. The PK parameters in lung samples were systematically higher than
      in serum. After multiple-dose administration of posaconazole, a significant
      accumulation of the drug was evident in lung tissue. The PK behavior of
      posaconazole in this particular experimental model is similar to that observed in
      humans. Thus, we believe this model could be a valid tool to evaluate
      posaconazole exposure-response relationship.

PMID- 27889254
TI  - The utility of direct specimen detection by Sanger sequencing in hospitalized
      pediatric patients.
AB  - Direct microbial DNA detection from clinical specimens by polymerase chain
      reaction and Sanger sequencing has been developed to address the innate
      limitations of traditional culture-based work-up. We report our institution's
      experience with direct specimen sequencing, its clinical utility, and barriers to
      effective clinical implementation.

PMID- 27889255
TI  - Antigenic variation of LaSota and genotype VII Newcastle disease virus (NDV) and
      their efficacy against challenge with velogenic NDV.
AB  - Continued monitoring and evaluation of vaccine efficacy against prevalent or
      newly isolated strains has great importance in advising Newcastle disease (ND)
      immunization strategy. In this study, we systematically analysed the antigenic
      variation between genotype VII NDV aSG10 and the commercial vaccine strain
      LaSota, and assessed their efficacy against challenge with velogenic NDV by
      serological analysis and animal testing. We show that these two viruses are
      antigenically distinguishable; anti-NDV aSG10 hyper-immune sera demonstrated
      higher haemagglutination inhibition (HI) titres (11.13+/-0.30log2) against the
      aSG10 virus, compared with titres against LaSota (9.53+/-0.50log2). Conversely,
      the hyper-immune sera from LaSota showed higher HI titres against LaSota virus
      (9.73+/-0.36log2), but 2-fold lower HI titre against aSG10 (8.87+/-0.38log2).
      Each serum neutralised heterologous virus, but neutralisation titres were always
      3- to 6-fold higher against its homologous strain than heterologous virus. The
      cross-reactivity R value between aSG10 and LaSota was 0.23, indicating that they
      are loosely related with major antigenic differences within a single serotype.
      The results of animal tests revealed that the aSG10 vaccine had a significantly
      higher protection rate than the LaSota vaccine against genotype VII NDV,
      regardless of intramuscular (IM) or eye drop/intranasal (ED/IN) route of SG10
      challenge. Compared with IM administration, chicken flocks needed higher HI
      antibody levels to obtain sufficient protection when challenged by the natural
      ED/IN route. These results are highly informative for better control of ND in the
      poultry industry.

PMID- 27889256
TI  - Controlled human infection with RSV: The opportunities of experimental challenge.
AB  - Despite the recent explosion in RSV vaccine development, there remain substantial
      hurdles to overcome before licensing of effective vaccines will allow widespread
      use, particularly in high-risk populations. Incomplete understanding of
      mechanisms and correlates of protection against RSV mean that, for the time
      being, successful RSV vaccines must directly demonstrate efficacy, which
      necessitates large and costly clinical trials in naturally infected patients. To
      mitigate the risks inherent in progressing to these late-stage trials,
      experimental human RSV infection studies have recently been re-established,
      representing the interface between pre-clinical models and observational studies
      of patients. Not only can they be used for early proof-of-concept clinical trials
      to test vaccine efficacy, but human challenge studies also offer the potential to
      better understand protective immunity against RSV infection to improve vaccine
      design and delivery. In the past, controlled human infection studies with RSV
      have been instrumental in elucidating the influence of factors such as route of
      infection and type of inoculum on the course of disease. Recently, efficacy
      trials of novel RSV antiviral drugs have also been successfully undertaken. Now,
      with advances in technology, detailed investigations of human mucosal immunity in
      the RSV-infected airway are possible. These have indicated defects in RSV-induced
      humoral and CD8+ T cell immunity that may contribute to the recurrent symptomatic
      infection that occurs throughout life and should be circumvented by optimal
      vaccines. Here, we discuss the insights derived from RSV human challenge models;
      the major impediments to their more widespread uptake; and their potential
      benefit in accelerating vaccine development, including future directions to
      further enhance the relevance of these models to at-risk patient populations.

PMID- 27889258
TI  - Unilateral collaboration: The practices and understandings of traditional birth
      attendants in southeastern Nigeria.
AB  - BACKGROUND: Despite the promotion of hospital-based maternity care as the safest
      option, for less developed countries, many women particularly those in the rural
      areas continue to patronise indigenous midwives or traditional birth attendants.
      Little is known about traditional birth attendants' perspectives regarding their
      pregnancy and birth practices. AIM: To explore traditional birth attendants'
      discourses of their pregnancy and birthing practices in southeast Nigeria.
      METHOD: Hermeneutic phenomenology guided by poststructural feminism was the
      methodological approach. Individual face to face semi-structured interviews were
      conducted with five traditional birth attendants following consent. FINDINGS:
      Participants' narratives of their pregnancy and birth practices are organised
      into two main themes namely: 'knowing differently,' and 'making a difference.'
      Their responses demonstrate evidence of expertise in sustaining normal birth,
      safe practice including hygiene, identifying deviation from the normal,
      willingness to refer women to hospital when required, and appropriate use of both
      traditional and western medicines. Inexpensive, culturally sensitive, and
      compassionate care were the attributes that differentiate traditional birth
      attendants' services from hospital-based maternity care. CONCLUSION: The
      participants provided a counter-narrative to the official position in Nigeria
      about the space they occupy. They responded in ways that depict them as committed
      champions of normal birth with ability to offer comprehensive care in accordance
      with the individual needs of women, and respect for cultural norms. Professional
      midwives are therefore challenged to review their ways of practice. Emphasis
      should be placed on what formal healthcare providers and traditional birth
      attendants can learn from each other.

PMID- 27889257
TI  - Translation and cultural adaptation of the Shame and Stigma Scale (SSS) into
      Portuguese (Brazil) to evaluate patients with head and neck cancer.
AB  - INTRODUCTION: Head and neck cancer is the sixth leading cause of death from
      cancer worldwide and its treatment may involve surgery, chemotherapy and/or
      radiation therapy. The surgical procedure may cause mutilating sequelae, that can
      alter patient self-image. Thus, head and neck cancer is often connected to the
      negative stigma with decreased quality of life. Few studies assess the social
      stigma and shame perceived by patients with head and neck cancer. OBJECTIVE: To
      perform the translation and cultural adaptation of the Shame and Stigma Scale
      (SSS) into Portuguese (Brazil). METHODS: Two independent translations (English
      into Portuguese) were carried out by two professionals fluent in the English
      language. After the synthesis of the translations, two independent back
      translations (from Portuguese into English) were performed by two translators
      whose native language is English. All translations were critically assessed by a
      committee of experts consisting of five members. A sample of 15 patients answered
      the Brazilian Portuguese version of the SSS to carry out the pretest. At this
      step, the patients were able to suggest modifications and evaluate the
      understanding of the items. RESULTS: There was no need to change the scale after
      this step. Based on the previous steps, we obtained the Portuguese (Brazil)
      version of the SSS, which was called "Escala de Vergonha e Estigma". CONCLUSION:
      The Portuguese (Brazil) version of the SSP was shown to be adequate to be applied
      to the population with HNC and, therefore, the psychometric properties of the
      tool will be evaluated during following steps.

PMID- 27889259
TI  - Episiotomy and severe perineal trauma among Eastern African immigrant women
      giving birth in public maternity care: A population based study in Victoria,
      Australia.
AB  - BACKGROUND: Eastern African immigrants from countries affected by female genital
      mutilation have resettled in many developed countries, including Australia.
      Although possibly at risk of perineal trauma and episiotomy, research
      investigating their perineal status post-migration is sparse. AIM: To investigate
      variations in episiotomy use and incidence of severe perineal tear for women born
      in Eritrea, Ethiopia, Somalia and Sudan compared with Australian-born women.
      METHODS: A population-based study of 203,206 Australian-born and 3502 Eastern
      African immigrant women admitted as public patients, with singleton vaginal
      births between 1999 and 2007, was conducted using the Victorian Perinatal Data
      Collection. Descriptive and multivariable logistic regression analysis adjusting
      for confounders selected a priori, were performed to compute incidence and
      adjusted odds ratios. FINDINGS: Overall, 30.5% Eastern African immigrants had
      episiotomy compared to 17.2% Australian-born women. Severe perineal trauma
      occurred in 2.1% of Eastern African immigrants and 1.6% of Australian-born women.
      While the odds of severe perineal trauma was significantly elevated only during
      non-instrumental vaginal births for Eastern African immigrants {ORadj1.56
      95%CI(1.17, 2.12)}; that of episiotomy was increased during both non-instrumental
      {ORadj4.47 95%CI(4.10, 4.88)} and instrumental {ORadj2.51 95%CI(1.91, 3.29)}
      vaginal births. CONCLUSIONS: Overall, Eastern African immigrant women experienced
      elevated odds of episiotomy and severe perineal tear. Health care providers need
      to be mindful of the increased risk of severe perineal tear in these women and
      enhance efforts in identification and treatment of severe perineal trauma to
      minimise associated short and long term morbidity. Strategies to reduce unneeded
      episiotomy and ways of enhancing perineal safety are also needed.

PMID- 27889260
TI  - Two Bistable Switches Govern M Phase Entry.
AB  - The abrupt and irreversible transition from interphase to M phase is essential to
      separate DNA replication from chromosome segregation. This transition requires
      the switch-like phosphorylation of hundreds of proteins by the cyclin-dependent
      kinase 1 (Cdk1):cyclin B (CycB) complex. Previous studies have ascribed these
      switch-like phosphorylations to the auto-activation of Cdk1:CycB through the
      removal of inhibitory phosphorylations on Cdk1-Tyr15 [1, 2]. The positive
      feedback in Cdk1 activation creates a bistable switch that makes mitotic
      commitment irreversible [2-4]. Here, we surprisingly find that Cdk1 auto
      activation is dispensable for irreversible, switch-like mitotic entry due to a
      second mechanism, whereby Cdk1:CycB inhibits its counteracting phosphatase
      (PP2A:B55). We show that the PP2A:B55-inhibiting Greatwall (Gwl)-endosulfine
      (ENSA) pathway is both necessary and sufficient for switch-like phosphorylations
      of mitotic substrates. Using purified components of the Gwl-ENSA pathway in a
      reconstituted system, we found a sharp Cdk1 threshold for phosphorylation of a
      luminescent mitotic substrate. The Cdk1 threshold to induce mitotic
      phosphorylation is distinctly higher than the Cdk1 threshold required to maintain
      these phosphorylations-evidence for bistability. A combination of mathematical
      modeling and biochemical reconstitution show that the bistable behavior of the
      Gwl-ENSA pathway emerges from its mutual antagonism with PP2A:B55. Our results
      demonstrate that two interlinked bistable mechanisms provide a robust solution
      for irreversible and switch-like mitotic entry.

PMID- 27889261
TI  - NIK/MAP3K14 Regulates Mitochondrial Dynamics and Trafficking to Promote Cell
      Invasion.
AB  - Although the role of NF-kappaB-inducing kinase (NIK) in immunity is well
      established, its relevance in cancer is just emerging. Here we describe novel
      functions for NIK in regulating mitochondrial dynamics and motility to promote
      cell invasion. We show that NIK is localized to mitochondria in cancer cell
      lines, ex vivo tumor tissue, and mouse embryonic fibroblasts (MEFs). NIK promotes
      mitochondrial fission, velocity, and directional migration, resulting in
      subcellular distribution of mitochondria to the periphery of migrating cells.
      Moreover, NIK is required for recruitment of Drp1 to mitochondria, forms a
      complex with Drp1, and regulates Drp1 phosphorylation at Ser-616 and
      dephosphorylation at Ser-637. Consistent with a role for NIK in regulating
      mitochondrial dynamics, we demonstrate that Drp1 is required for NIK-dependent,
      cytokine-induced invasion. Importantly, using MEFs, we demonstrate that the
      established downstream mediators of NIK signaling, IkappaB kinase alpha/beta
      (IKKalpha/beta) and NF-kappaB, are not required for NIK to regulate cell
      invasion, Drp1 mitochondrial localization, or mitochondrial fission. Our results
      establish a new paradigm for IKK-independent NIK signaling and significantly
      expand the current dogma that NIK is predominantly cytosolic and exclusively
      regulates NF-kappaB activity. Overall, these findings highlight the importance of
      NIK in tumor pathogenesis and invite new therapeutic strategies that attenuate
      mitochondrial dysfunction through inhibition of NIK and Drp1.

PMID- 27889262
TI  - Injections of Predatory Bacteria Work Alongside Host Immune Cells to Treat
      Shigella Infection in Zebrafish Larvae.
AB  - Bdellovibrio bacteriovorus are predatory bacteria that invade and kill a range of
      Gram-negative bacterial pathogens in natural environments and in vitro [1, 2]. In
      this study, we investigated Bdellovibrio as an injected, antibacterial treatment
      in vivo, using zebrafish (Danio rerio) larvae infected with an antibiotic
      resistant strain of the human pathogen Shigella flexneri. When injected alone,
      Bdellovibrio can persist for more than 24 hr in vivo yet exert no pathogenic
      effects on zebrafish larvae. Bdellovibrio injection of zebrafish containing a
      lethal dose of Shigella promotes pathogen killing, leading to increased zebrafish
      survival. Live-cell imaging of infected zebrafish reveals that Shigella undergo
      rounding induced by the invasive predation from Bdellovibrio in vivo.
      Furthermore, Shigella-dependent replication of Bdellovibrio was captured inside
      the zebrafish larvae, indicating active predation in vivo. Bdellovibrio can be
      engulfed and ultimately eliminated by host neutrophils and macrophages, yet have
      a sufficient dwell time to prey on pathogens. Experiments in immune-compromised
      zebrafish reveal that maximal therapeutic benefits of Bdellovibrio result from
      the synergy of both bacterial predation and host immunity, but that in vivo
      predation contributes significantly to the survival outcome. Our results
      demonstrate that successful antibacterial therapy can be achieved via the host
      immune system working together with bacterial predation by Bdellovibrio. Such
      cooperation may be important to consider in the fight against antibiotic
      resistant infections in vivo.

PMID- 27889263
TI  - Shade Promotes Phototropism through Phytochrome B-Controlled Auxin Production.
AB  - Phototropism is an asymmetric growth response enabling plants to optimally
      position their organs. In flowering plants, the phototropin (phot) blue light
      receptors are essential to detect light gradients. In etiolated seedlings, the
      phototropic response is enhanced by the red/far-red (R/FR)-sensing phytochromes
      (phy) with a predominant function of phyA. In this study, we analyzed the
      influence of the phytochromes on phototropism in green (de-etiolated) Arabidopsis
      seedlings. Our experiments in the laboratory and outdoors revealed that, in open
      environments (high R/FR ratio), phyB inhibits phototropism. In contrast, under
      foliar shade, where access to direct sunlight becomes important, the phototropic
      response was strong. phyB modulates phototropism, depending on the R/FR ratio, by
      controlling the activity of three basic-helix-loop-helix (bHLH) transcription
      factors of the PHYTOCHROME INTERACTING FACTORs (PIFs) family. Promotion of
      phototropism depends on PIF-mediated induction of several members of the YUCCA
      gene family, leading to auxin production in the cotyledons. Our study identifies
      PIFs and YUCCAs as novel molecular players promoting phototropism in
      photoautotrophic, but not etiolated, seedlings. Moreover, our findings reveal
      fundamental differences in the phytochrome-phototropism crosstalk in etiolated
      versus green seedlings. We propose that in natural conditions where the light
      environment is not homogeneous, the uncovered phytochrome-phototropin co-action
      is important for plants to adapt their growth strategy to optimize photosynthetic
      light capture.

PMID- 27889264
TI  - Recall of Others' Actions after Incidental Encoding Reveals Episodic-like Memory
      in Dogs.
AB  - The existence of episodic memory in non-human animals is a debated topic that has
      been investigated using different methodologies that reflect diverse theoretical
      approaches to its definition. A fundamental feature of episodic memory is
      recalling after incidental encoding, which can be assessed if the recall test is
      unexpected [1]. We used a modified version of the "Do as I Do" method [2],
      relying on dogs' ability to imitate human actions, to test whether dogs can rely
      on episodic memory when recalling others' actions from the past. Dogs were first
      trained to imitate human actions on command. Next, they were trained to perform a
      simple training exercise (lying down), irrespective of the previously
      demonstrated action. This way, we substituted their expectation to be required to
      imitate with the expectation to be required to lie down. We then tested whether
      dogs recalled the demonstrated actions by unexpectedly giving them the command to
      imitate, instead of lying down. Dogs were tested with a short (1 min) and a long
      (1 hr) retention interval. They were able to recall the demonstrated actions
      after both intervals; however, their performance declined more with time compared
      to conditions in which imitation was expected. These findings show that dogs
      recall past events as complex as human actions even if they do not expect the
      memory test, providing evidence for episodic-like memory. Dogs offer an ideal
      model to study episodic memory in non-human species, and this methodological
      approach allows investigating memory of complex, context-rich events. VIDEO
      ABSTRACT.

PMID- 27889265
TI  - Integration of Phytochrome and Cryptochrome Signals Determines Plant Growth
      during Competition for Light.
AB  - Plants in dense vegetation perceive their neighbors primarily through changes in
      light quality. Initially, the ratio between red (R) and far-red (FR) light
      decreases due to reflection of FR by plant tissue well before shading occurs.
      Perception of low R:FR by the phytochrome photoreceptors induces the shade
      avoidance response [1], of which accelerated elongation growth of leaf-bearing
      organs is an important feature. Low R:FR-induced phytochrome inactivation leads
      to the accumulation and activation of the transcription factors PHYTOCHROME
      INTERACTING FACTORs (PIFs) 4, 5, and 7 and subsequent expression of their growth
      mediating targets [2, 3]. When true shading occurs, transmitted light is
      especially depleted in red and blue (B) wavelengths, due to absorption by
      chlorophyll [4]. Although the reduction of blue wavelengths alone does not occur
      in nature, long-term exposure to low B light induces a shade avoidance-like
      response that is dependent on the cryptochrome photoreceptors and the
      transcription factors PIF4 and PIF5 [5-7]. We show in Arabidopsis thaliana that
      low B in combination with low R:FR enhances petiole elongation similar to
      vegetation shade, providing functional context for a low B response in plant
      competition. Low B potentiates the low R:FR response through PIF4, PIF5, and
      PIF7, and it involves increased PIF5 abundance and transcriptional changes. Low B
      attenuates a low R:FR-induced negative feedback loop through reduced gene
      expression of negative regulators and reduced HFR1 levels. The enhanced response
      to combined phytochrome and cryptochrome inactivation shows how multiple light
      cues can be integrated to fine-tune the plant's response to a changing
      environment.

PMID- 27889266
TI  - The effect anticoagulation status on geriatric fall trauma patients.
AB  - BACKGROUND: This research study aims to identify the effect of anticoagulation
      status on hospital course, complications, and outcomes among geriatric fall
      trauma patients. METHODS: The study design is a retrospective cohort study,
      looking at fall trauma among patients aged 60 to 80 years from 2009 to 2013 at a
      university hospital in the United States. The statistical analysis, conducted
      with SPSS software with a threshold for statistical significance of P < .05, was
      stratified by anticoagulation status and then further by type of anticoagulation
      (aspirin, warfarin, clopidogrel, enoxaparin, and dipyridamole). Outcomes
      variables include mortality, length of stay (LOS), intensive care unit (ICU)
      admission, and complications. RESULTS: The total number of patients included in
      this study was 1,121. Compared with patients not on anticoagulation, there was a
      higher LOS among patients on anticoagulation (6.3 +/- 6.2 vs 4.9 +/- 5.2, P =
      .001). A higher LOS (7.2 +/- 6.8 vs 5.0 +/- 5.3, P = .001) and days in the ICU
      (2.1 +/- 5.4 vs 1.1 +/- 3.8, P = .010) was observed in patients on warfarin. A
      higher mortality (7.1% vs 2.8%, P = .013), LOS (6.3 +/- 6.2 vs 5.1 +/- 5.396, P =
      .036), and complication rate (49.1 vs 36.7, P = .010) was observed among patients
      on clopidogrel. CONCLUSIONS: In this study, a higher mortality and complication
      rate were seen among clopidogrel, and a greater LOS and number of days in the ICU
      were seen in patients on warfarin. These differences are important, as they can
      serve as a screening tool for triaging the severity of a geriatric trauma
      patient's condition and complication risk. For patients on clopidogrel, it is
      essential that these patients are recognized early as high-risk patients who will
      need to be monitored more closely. For patients on clopidogrel or warfarin,
      bridging a patient's anticoagulation should be initiated as soon as possible to
      prevent unnecessary increased LOS. At last, these data also provide support
      against prescribing patients clopidogrel when other anticoagulation options are
      available.

PMID- 27889267
TI  - Attribution 2.0: whose complication is it?
AB  - BACKGROUND: Payment models aimed at improving quality and curbing costs are being
      deployed, and hospitals are evaluating complications more closely. To decrease
      complications, hospitals must first "attribute" them to a responsible party. Our
      study uses a rigorous approach to attribution in the trauma population. METHODS:
      Twelve months of complications were reviewed by a multidisciplinary panel.
      Physicians, patients, nursing, and the hospital were all incorporated into the
      model. A point system was developed for each complication. Fractional points were
      given when multiple parties were involved. RESULTS: One hundred twenty-five
      complications were analyzed. Complications were attributed as follows: 30%
      neurosurgery, 22% trauma surgery (100% using the traditional method), 17%
      orthopedic surgery, 14% nursing, 9.6% plastics, 3.8% hospital, 1.6% patient, 1.4%
      urology, and .6% vascular. CONCLUSIONS: Up to 78% of complications were
      incorrectly ascribed using the traditional method. Almost 20% of complications
      resulted from factors outside the physician's control. Before complications can
      be reduced, their most proximate cause must be identified. Surgeons should own
      these data and lead the effort to improve quality and decrease complications.

PMID- 27889268
TI  - Evaluating surgical management and outcomes of colovaginal fistulas.
AB  - BACKGROUND: Colovaginal fistula is a rare condition associated with significant
      morbidity. The literature characterizing colovaginal fistula repair is sparse. We
      present our institution's experience treating colovaginal fistulas. METHODS: A
      retrospective review of all patients surgically treated for colovaginal fistula
      between 2005 and 2015 was performed. Patient demographics, intra-operative
      details, and post-operative outcomes were reviewed. RESULTS: We identified 27
      patients with a mean age of 71 (+/-13) and BMI of 30 (+/-9). The most common
      etiology for fistula was diverticulitis (n = 24, 89%). A laparoscopic approach
      was initiated in 19 patients (70%) and an open approach for 8 (30%) with 8
      patients converted from laparoscopy to open (42%). At a mean follow-up of 18
      months (+/-21), there were no recurrences. CONCLUSION: We present one of the
      largest series of the surgical management of colovaginal fistulas. Although our
      conversion rate was high, we recommend a laparoscopic approach be utilized when
      feasible.

PMID- 27889269
TI  - Medical student expectations from surgical education: A two-year institutional
      experience.
AB  - BACKGROUND: The third-year surgical rotation is the first exposure medical
      students have to the fundamentals of surgical education. It is known that medical
      students come to the surgical clerkship with preconceived ideas, many of them
      negative and based on prior student feedback and hearsay. METHODS: An anonymous
      survey was conducted of third-year medical students while on the surgical
      clerkship. We sought to quantify student's experiences and expectations by
      assessing the students' confidence levels before and after the rotation. RESULTS:
      Over a 26 month period from July 2013-August 2015, 250 surveys were conducted. In
      terms of confidence gained on the surgical rotation, students reported a
      statistically significant (p < 0.01) increase in confidence in fifteen different
      areas of interest. However, in terms of expectations, students reported
      discordance between anticipated experience and actual experience. Students'
      responses indicate that students felt confident with their knowledge of diseases;
      however, they desire more involvement in complex patient care and procedural
      skills. CONCLUSIONS: The third-year clerkship is the first exposure to surgery
      for many medical students. Surgical educators are tasked with providing a
      foundation for clinical medicine; however, students have expressed an expectation
      to be more involved with complex patient care and management.

PMID- 27889270
TI  - Does implementing a general surgery residency program and resident involvement
      affect patient outcomes and increase care-associated charges?
AB  - BACKGROUND: Variable results regarding general surgery residency program (GSRP)
      impact on patient outcomes and charges are reported. The aim of this study was to
      determine any significant differences in patient outcomes and cost with a new
      GSRP. METHODS: We analyzed all laparoscopic appendectomies (lap-ap),
      cholecystectomies (lap-chole), and inguinal hernia repairs (IHR) performed before
      and after implementing a GRSP. RESULTS: Operative time significantly increased
      for lap-ap (p < 0.0001), lap-chole (p < 0.0001) and IHR (p = 0.03). Time to close
      the incision significantly increased for lap-ap (p < 0.0001), lap-chole (p =
      0.006) and IHR (p = 0.03). Length of stay only increased for lap-ap (p = 0.04).
      Complication rates did not increase for any procedure. However, charges
      significantly increased for lap-ap (p < 0.0001), lap-chole (p < 0.0001), and IHR
      (p = 0.03). CONCLUSIONS: Although a newly implemented GSRP caused increases in
      overall operative times, times to close incisions, and charges, it did not
      negatively impact patient outcomes.

PMID- 27889271
TI  - Assessment of perioperative nutrition practices and attitudes-A national survey
      of colorectal and GI surgical oncology programs.
AB  - BACKGROUND: Implementation of evidence-based peri-operative nutrition in the U.S.
      is poorly described and hypothesized to be suboptimal. This study broadly
      describes practices and attitudes regarding nutrition screening/intervention in
      U.S. gastrointestinal and oncologic surgeons. METHODS: Nationwide nutritional
      practice survey of GI/Oncologic surgical faculty. RESULTS: Program response rates
      were 57% and 81% for colorectal and oncology fellowships, respectively. Only 38%
      had formal nutritional screening processes in place. Average estimated percent of
      patients malnourished, receiving nutritional screening, and receiving nutritional
      supplementation preoperatively were 28%, 43%, and 21%, respectively. University
      affiliation (p = 0.0371) and a formal screening process (p = 0.0312) predicted
      higher preoperative nutritional screening rates. Controversy existed regarding
      routine use of perioperative immunonutrition, but strong consensus emerged that
      lack of awareness regarding positive data for immunonutrition impedes usage.
      CONCLUSION: U.S. surgeons recognize importance of perioperative nutritional
      screening and benefits of basic nutrition therapy. However, limited formal
      nutrition screening programs currently exist indicating a significant need for
      implementation of nutrition screening and basic nutrition intervention. Further
      work on education, implementation and identifying clinical research needs for
      immunonutrition interventions is also vitally needed. SUMMARY: This study broadly
      describes nutritional practices and attitudes of gastrointestinal and oncologic
      surgeons across the U.S. Surgeons recognize both the importance of proper
      perioperative surgical nutritional support and the potential value to their
      practice in terms of outcomes, but this study confirms poor implementation of
      evidence-based nutrition practices in GI and oncologic surgery programs. This
      study describes a significant opportunity to capitalize on current favorable
      surgeon beliefs (and positive published data) regarding the benefit of
      perioperative nutrition to improve surgical nutrition practice and patient
      outcomes in the U.S.

PMID- 27889272
TI  - Can muscle coordination explain the advantage of using the standing position
      during intense cycling?
AB  - OBJECTIVES: When compared to seated, the standing position allows the production
      of higher power outputs during intense cycling. We hypothesized that muscle
      coordination could explain this advantage. To test this hypothesis, we assessed
      muscle activity over a wide range of power outputs for both seated and standing
      cycling positions. DESIGN: Nine lower limb muscle activities from seventeen
      untrained volunteers were recorded during cycling sequences performed in the
      seated and the standing positions at power outputs ranging from ~100 to 700W at
      90+/-5 revolutions-per-minute (RPM). METHODS: Integrated electromyography
      activity (iEMG), temporal patterns of the EMGs, and muscle synergies were
      analyzed. RESULTS: Muscle activity was underlain by four muscle synergies in both
      positions. Muscle synergies were similar in the two positions (Pearson's
      r=0.929+/-0.125). The activation patterns of knee and ankle extensor muscles and
      their associated synergies had different timings in the two positions
      (differences of ~2-10% of cycle). No major timing changes were observed with
      power output (<2% of cycle). Differences in iEMG between the two positions
      depended strongly on power output in all but the calf muscle (medial
      gastrocnemius). CONCLUSIONS: The number and structure of the muscle synergies
      play a minor role in the advantage of using the standing position when cycling at
      high power-outputs. However, the standing position is favorable in terms of iEMG
      at power outputs ?500-600W due to position-dependent modulations of muscle
      activation levels. These data are important for understanding the determinants of
      the seat-stand transition in cycling.

PMID- 27889274
TI  - A tale of 2 HIV outbreaks caused by unsafe injections in Cambodia and the United
      States, 2014-2015.

PMID- 27889273
TI  - Is subscapularis recruited in a similar manner during shoulder internal rotation
      exercises and belly press and lift off tests?
AB  - OBJECTIVES: Although the belly press and lift off tests are recommended to assess
      subscapularis function, shoulder internal rotation (IR) exercises performed in
      other shoulder positions are more commonly used to restore subscapularis
      function. It is not known if shoulder IR exercises specifically activate
      subscapularis to the same degree as the lift off and belly press tests, and thus
      have the potential to effect subscapularis strength gains. Therefore, the aim was
      to compare subscapularis activation levels with those of other shoulder internal
      rotator muscles during the belly press and lift off tests and shoulder IR
      exercise positions. DESIGN: Original research. METHODS: Twenty asymptomatic
      volunteers performed maximal isometric contractions during the belly press and
      lift off tests and shoulder IR performed at 90 degrees  and 0 degrees  abduction
      in an upright position and supported at 90 degrees  abduction in supine. Muscle
      activation levels were recorded using a combination of indwelling and surface
      electrodes. Data were normalized to maximum voluntary contractions and averaged.
      RESULTS: Moderate average subscapularis activation levels were recorded during
      all shoulder IR tasks examined with no significant difference between tasks
      (p=0.18). The belly press test was the only IR task in which subscapularis
      activation levels were significantly higher than all other shoulder internal
      rotator muscles (p<0.05). CONCLUSIONS: Shoulder IR exercises activate
      subscapularis to similar moderate levels as the belly press and lift off tests
      and therefore, have similar potential to strengthen subscapularis. However, the
      belly press test, with significantly higher subscapularis activation than other
      shoulder internal rotators, more specifically targets subscapularis.

PMID- 27889275
TI  - Preconceptions about the infection process among prenursing students.
AB  - Two hundred seven prenursing students in a large university-based nursing college
      participated in a study about their preconceptions concerning the infection
      process. Most students had a poor understanding of the distinction between
      bacteria and viruses and had little knowledge about the immune system or the
      mechanism of action of antibiotics. Instructors can use knowledge of student
      preconceptions to create more relevant learning experiences.

PMID- 27889276
TI  - Perceived effectiveness of messages promoting hand hygiene.
AB  - Eighty-six infection control specialists evaluated 24 messages promoting hand
      hygiene (HH). Brief, simple messages using appeals to social situations and to
      ego (self-efficacy) were rated as most likely to increase HH compliance.

PMID- 27889278
TI  - Safety and efficacy of NEPA, an oral fixed combination of netupitant and
      palonosetron, in older patients.
AB  - OBJECTIVES: Prevention of chemotherapy-induced nausea and vomiting is critical in
      older patients with cancer. NEPA is an oral fixed combination of netupitant
      300mg, a new NK1 receptor antagonist (RA), and palonosetron 0.5mg, a
      pharmacologically distinct 5-HT3 RA. This retrospective analysis evaluated the
      efficacy and safety of NEPA in older patients. METHODS: Patients aged >=65 and
      >=70years from one phase II and two phase III trials were considered.
      Chemotherapy-naive patients with malignant tumors were treated with anthracycline
      cyclophosphamide (AC), non-AC-based moderately emetogenic chemotherapy (non-AC
      MEC), or highly emetogenic chemotherapy (HEC). Following single-dose NEPA,
      patients received oral dexamethasone on day 1 (AC and non-AC MEC) or days 1-4
      (HEC). Efficacy was evaluated through complete response (CR) in cycle 1. Safety
      was evaluated by AEs and ECGs. Data were summarized by descriptive statistics.
      RESULTS: Overall, 214 patients were >=65years and 80 were >=70years. A higher CR
      was observed in older patients versus the total population; in the acute phase
      >90% of patients >=65years experienced CR. Efficacy was maintained over multiple
      cycles of chemotherapy. No significant nausea rates were generally higher in the
      older patients versus total population. Similar rates of AEs in the first
      treatment cycle were reported for patients >=65years, >=70years, and total
      population (72.9% vs 67.5% vs 70.0%, respectively). No cardiac safety concerns
      were raised. CONCLUSION: NEPA is highly effective in older patients receiving MEC
      or HEC regimens. NEPA is also well tolerated, demonstrating suitability for use
      in older patients who may have comorbidities.

PMID- 27889277
TI  - Evaluating the Four Kallikrein Panel of the 4Kscore for Prediction of High-grade
      Prostate Cancer in Men in the Canary Prostate Active Surveillance Study.
AB  - BACKGROUND: Diagnosis of Gleason 6 prostate cancer can leave uncertainty about
      the presence of undetected aggressive disease. OBJECTIVE: To evaluate the utility
      of a four kallikrein (4K) panel in predicting the presence of high-grade cancer
      in men on active surveillance. DESIGN, SETTING, AND PARTICIPANTS: Plasma
      collected before the first and subsequent surveillance biopsies was assessed for
      718 men prospectively enrolled in the multi-institutional Canary PASS trial.
      Biopsy data were split 2:1 into training and test sets. We developed statistical
      models that included clinical information and either the 4Kpanel or serum
      prostate-specific antigen (PSA). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:
      The endpoint was reclassification to Gleason >=7. We used receiver operating
      characteristic (ROC) curve analyses and area under the curve (AUC) to assess
      discriminatory capacity, and decision curve analysis (DCA) to report clinical net
      benefit. RESULTS AND LIMITATIONS: Significant predictors for reclassification
      were 4Kpanel (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31-1.81) or
      PSA (OR 2.11, 95% CI 1.53-2.91), >=20% cores positive (OR 2.10, 95% CI 1.33
      3.32), two or more prior negative biopsies (OR 0.19, 95% CI 0.04-0.85), prostate
      volume (OR 0.47, 95% CI 0.31-0.70), and body mass index (OR 1.09, 95% CI 1.04
      1.14). ROC curve analysis comparing 4K and base models indicated that the 4Kpanel
      improved accuracy for predicting reclassification (AUC 0.78 vs 0.74) at the first
      surveillance biopsy. Both models performed comparably for prediction of
      reclassification at subsequent biopsies (AUC 0.75 vs 0.76). In DCA, both models
      showed higher net benefit compared to biopsy-all and biopsy-none strategies.
      Limitations include the single cohort nature of the study and the small numbers;
      results should be validated in another cohort before clinical use. CONCLUSIONS:
      The 4Kpanel provided incremental value over routine clinical information in
      predicting high-grade cancer in the first biopsy after diagnosis. The 4Kpanel did
      not add predictive value to the base model at subsequent surveillance biopsies.
      PATIENT SUMMARY: Active surveillance is a management strategy for many low-grade
      prostate cancers. Repeat biopsies monitor for previously undetected high-grade
      cancer. We show that a model with clinical variables, including a panel of four
      kallikreins, indicates the presence of high-grade cancer before a biopsy is
      performed.

PMID- 27889279
TI  - Vitamin K epoxide reductase expression and prostate cancer risk.
AB  - PURPOSE: Increasing evidence has demonstrated that men taking the anticoagulant
      warfarin have a lower risk of developing prostate cancer. This phenomenon is not
      observed in other cancers. We sought to determine if the target of warfarin,
      vitamin K epoxide reductase (VKOR), is expressed in benign and cancerous prostate
      tissues and if a functional single nucleotide polymorphism (SNP) in the VKOR gene
      is associated with prostate cancer risk. MATERIALS AND METHODS: The expression of
      VKOR was quantified by immunohistochemistry in an institutional series of 54
      radical prostatectomy samples and metastatic biopsies, as well as in 40 other
      cancers and matched benign tissues on a tissue microarray. Genotyping of SNP
      rs2359612 was performed in a prospective series of 57 patients. RESULTS: VKOR is
      highly expressed in benign human prostate epithelial cells but is not expressed
      or expressed at very low levels in cancerous cells. This expression pattern is
      unique to prostate cancer. Additionally, the proportion of the carrier C allele
      of rs2359612 in the patients with prostate cancer was significantly higher than
      in the population, suggesting an association between this allele and the risk of
      having a diagnosis of prostate cancer. CONCLUSIONS: The expression of VKOR in
      benign prostate epithelial cells, along with the association between a functional
      VKOR SNP and prostate cancer risk, suggests a possible role for VKOR in mediating
      the effect of warfarin on prostate cancer risk. Larger multi-institutional cohort
      studies are warranted, as are molecular studies on the role of VKOR in prostate
      cancer development.

PMID- 27889280
TI  - Percutaneous biopsy in large, locally advanced or metastatic renal tumors.
AB  - INTRODUCTION: The role of percutaneous biopsy to characterize large, locally
      advanced and metastatic primary renal tumors has not been well described. The
      goal of this article is to describe the potential advantages of biopsy for
      preoperative evaluation of patients with large renal tumors and advanced disease.
      METHODS: Literature was reviewed for percutaneous biopsy and for locally advanced
      and metastatic renal tumors. RESULTS: Multiple studies have confirmed that
      percutaneous biopsy is safe, and the cost is minimal relative to the cost of
      surgical operation. Biopsy of large masses should obtain multiple core samples
      from several sites with tumors to decrease error from sampling heterogeneous
      tumors. CONCLUSIONS: Potential advantages of biopsy for large renal masses
      include identification of patients for retroperitoneal lymph node dissection who
      may have occult lymph node metastasis. In patients with metastatic renal cell
      carcinoma, biopsy characterizes tumors for patients who may not benefit from
      cytoreductive surgical operation. The role of biopsy is likely to expand in the
      future with the development of advanced molecular tools for risk stratification.

PMID- 27889281
TI  - Is structural stigma's effect on the mortality of sexual minorities robust? A
      failure to replicate the results of a published study.
AB  - BACKGROUND: The study of stigma's influence on health has surged in recent years.
      Hatzenbuehler et al.'s (2014) study of structural stigma's effect on mortality
      revealed an average of 12 years' shorter life expectancy for sexual minorities
      who resided in communities thought to exhibit high levels of anti-gay prejudice,
      using data from the 1988-2002 administrations of the US General Social Survey
      linked to mortality outcome data in the 2008 National Death Index. METHODS: In
      the original study, the key predictor variable (structural stigma) led to results
      suggesting the profound negative influence of structural stigma on the mortality
      of sexual minorities. Attempts to replicate the study, in order to explore
      alternative hypotheses, repeatedly failed to generate the original study's key
      finding on structural stigma. Efforts to discern the source of the disparity in
      results revealed complications in the multiple imputation process for missing
      values of the components of structural stigma. This prompted efforts at
      replication using 10 different imputation approaches. RESULTS: Efforts to
      replicate Hatzenbuehler et al.'s (2014) key finding on structural stigma's
      notable influence on the premature mortality of sexual minorities, including a
      more refined imputation strategy than described in the original study, failed. No
      data imputation approach yielded parameters that supported the original study's
      conclusions. Alternative hypotheses, which originally motivated the present
      study, revealed little new information. CONCLUSION: Ten different approaches to
      multiple imputation of missing data yielded none in which the effect of
      structural stigma on the mortality of sexual minorities was statistically
      significant. Minimally, the original study's structural stigma variable (and
      hence its key result) is so sensitive to subjective measurement decisions as to
      be rendered unreliable.

PMID- 27889282
TI  - Neuromodulation Treatments for Geriatric Mood and Cognitive Disorders.
AB  - There is increasing evidence for the efficacy of neuromodulation in the treatment
      of resistant mood disorders and emerging data supporting the use of
      neuromodulation in cognitive disorders. A significant minority of depressed
      elders do not respond to pharmacotherapy and/or psychotherapy. This has led
      clinicians to recommend the increasing use of electroconvulsive therapy (ECT) in
      the treatment of medication-resistant or life-threatening geriatric depression.
      Multiple studies have supported the safety and efficacy of ECT in the elderly,
      yet ECT is associated with side effects including cardiovascular and cognitive
      side effects. Neuromodulation therapies have the potential for providing
      effective treatment for treatment-resistant older adults with reduced side
      effects and this review will outline the risks and benefits of neuromodulation
      treatment in geriatric psychiatry. There is also emerging evidence of the
      efficacy of neuromodulation devices in the treatment of cognitive disorders.
      Pharmacotherapy has been largely ineffective in changing the course of
      neurodegenerative diseases causing dementia and other treatments are clearly
      needed. This review will outline the available evidence for neuromodulation in
      the treatment of mood and cognitive disorders in the elderly.

PMID- 27889283
TI  - Suicidal Ideation and Social Capital: Community Matters.

PMID- 27889284
TI  - Perceived Stress: A Mechanism for Cognitive Decline Among Minorities?

PMID- 27889285
TI  - Aberrant left vertebral artery transposition and concomitant carotid-subclavian
      bypass for treatment of acute intramural hematoma with thoracic endovascular
      aortic repair.
AB  - Aberrant left vertebral artery (LVA) origin off the aortic arch is an uncommon
      anatomic variant. Treatment of the thoracic aortic pathology that necessitates
      its coverage has not been described. We present a patient with an acute
      intramural hematoma with a dominant LVA originating from the aortic arch. A LVA
      to-carotid artery transposition with shunt placement, carotid-to-subclavian
      bypass, and thoracic endovascular aortic repair were performed. The patient
      recovered uneventfully, without any evidence of stroke. This case study shows
      that aberrant left vertebral anatomy presents a unique and interesting challenge
      and that vertebral shunt techniques during revascularization can be performed
      without stroke.

PMID- 27889286
TI  - Computational fluid analysis of symptomatic chronic type B aortic dissections
      managed with the Streamliner Multilayer Flow Modulator.
AB  - OBJECTIVE: Managing symptomatic chronic type B aortic dissection (SCTBAD) by the
      Streamliner Multilayer Flow Modulator (SMFM) stent (Cardiatis, Isnes, Belgium) is
      akin to provisional structural support to induce complete attachment of the
      dissection flap, but with the ability of aortic remolding. This study
      investigated the SMFM's capability to enact healing of SCTBAD. METHODS: Clinical
      data for 12 cases comprising preoperative and postoperative treatment of SCTBAD
      were obtained from a multicenter database hosted by the Multilayer Flow Modulator
      Global Registry, Ireland. A biomechanical analysis, by means of computational
      fluid dynamics modeling, of the hemodynamic effects and branch patency associated
      with the use of the SMFM was performed for all cases. The mean length of the
      dissections was 30.23 +/- 13.3 cm. There were 30 SMFMs used, which covered 69
      aortic branches. RESULTS: At 1-year follow-up, the true lumen volume increased
      from 175.74 +/- 98.83 cm3 to 209.87 +/- 128.79 cm3; the false lumen decreased
      from 135.2 +/- 92.03 cm3 to 123.19 +/- 110.11 cm3. The false lumen index
      decreased from 0.29 +/- 0.13 (preoperatively) to 0.21 +/- 0.15 (postoperatively).
      The primary SMFM treatment of SCTBAD increased carotid perfusion by 35% +/- 21%
      (P = .0216) and suprarenal perfusion by 78% +/- 32% (P = .001). The wall pressure
      distribution blended along the newly enlarged true lumen, whereas the false lumen
      wall pressure decreased by 6.23% +/- 4.81% for the primary group (cases 1-7) and
      by 3.84% +/- 2.59% for the secondary group (cases 8-12). CONCLUSIONS: SMFM
      reduces the false lumen wall pressure through flow modulation. It preserves
      patency of all branches, minimizing the incidence of short-term complications.
      The SMFM is a valuable option in managing primary SCTBAD, without midterm
      complications.

PMID- 27889287
TI  - Structure-activity relationship study of a small cyclic peptide H-c[Lys-Pro-Glu]
      Arg-OH: a potent inhibitor of Vascular Endothelial Growth Factor interaction with
      Neuropilin-1.
AB  - Inhibition of angiogenesis is one of the most promising approaches in anticancer
      therapy. It was recently suggested that Neuropilin-1 (NRP-1) in tumour cells may
      serve as a separate receptor for Vascular Endothelial Growth Factor-165 (VEGF165)
      which is one of the main pro-angiogenic agents in the organism. Therefore
      molecules inhibiting VEGF165 binding to NRP-1 could be potential candidates for
      new antiangiogenic and anticancer drugs. Here we present a structure-activity
      relationship study of the peptide H-c[Lys-Pro-Glu]-Arg-OH which showed high
      inhibitory effect on VEGF165/NRP-1 binding (IC50=0.18MUM) in our previous study.
      We report the design, synthesis, in vitro assays and docking analysis of four
      small cyclic peptides (14-,15-membered ring) and one bigger cyclic compound (30
      membered ring). Our study shows that both the ring size and configuration of
      amino acid residues present in the structure are crucial for high inhibitory
      effect.

PMID- 27889288
TI  - Quiet dissent: The attitudes, beliefs and behaviours of UK osteopaths who reject
      low back pain guidance - A qualitative study.
AB  - INTRODUCTION: Clinical guidelines are derived from best research evidence and aim
      to: improve quality of non-specific low back pain (nsLBP) management and identify
      patients at risk of suffering chronic pain. However, guideline discordant
      attitudes and beliefs have been identified in healthcare students and
      practitioners, including osteopaths. DESIGN: A qualitative approach with elements
      of grounded theory was used to explore underlying attitudes and beliefs of
      practitioners/students working in a British osteopathic education institution.
      All participants rejected guideline recommendations for managing nsLBP. A
      constant comparative method was used to code and analyse emergent themes from
      transcript data. SUBJECTS: Purposive sampling identified 5 clinic tutors and 7
      students; all participated in semi-structured interviews. INTERPRETATION: Our
      central theme was a 'Precedence of Osteopathy' over medicine and other manual
      therapies. Three subthemes were: 1) beliefs about self; 2) perceptions of others;
      3) attitudes to guidelines and research. CONCLUSION: Participants possess a
      strong professional identity fostered by their education. This bestows autonomy,
      authority and distinctness upon them. The central theme was modelled as a lens
      through which participants viewed research: the evidence pyramid appears
      inverted, explaining why participants value expert opinion above all other
      evidence. Guidelines and research are perceived to threaten professional
      identity. In contractual situations that oblige practitioners to follow
      guidelines management, perhaps reflecting a pragmatic response to health-care
      market forces, clinical practice is modified. Developing further understanding of
      osteopaths' attitudes and beliefs and behaviour in respect of evidence-based
      guidance in education is important to enhance the quality of clinical practice in
      osteopathy.

PMID- 27889289
TI  - Increasing prevalence and incidence of multiple sclerosis in Poland.
AB  - Epidemiologic data on multiple sclerosis (MS) in Poland are limited. Our
      objectives were to assess a mean annual incidence rate, and MS prevalence on
      December 31, 2015 in the Swietokrzyskie province (central Poland). We analyzed
      data of 1525 patients, collected in the Polish Multiple Sclerosis Registry. On
      December 31, 2015, overall crude prevalence of MS was not less than 121.3/100,000
      (95% CI, 114.6-128.4). Significantly higher prevalence was recorded in females
      (167.1; 95% CI, 155.6-179.1) than in males (73.2; 95% CI, 64.2-82.6; P<0.001).
      The age-adjusted prevalence standardized to the European standard population was
      114.2/100,000 (95% CI, 106.2-121.5). The female-male ratio was 2.4:1. The mean
      annual incidence was 4.5/100,000 (95% CI, 3.8-5.2). Increased MS prevalence and
      incidence compared to 2010 and previous studies from Poland confirmed that
      central Poland is a high risk area for MS.

PMID- 27889290
TI  - Randomized, split-body, single-blinded clinical trial of topical broccoli sprout
      extract: Assessing the feasibility of its use in keratin-based disorders.
AB  - BACKGROUND: Epidermolysis bullosa simplex is a skin-blistering disorder caused by
      mutations in keratin (K)14 or K5. Treatment with nuclear factor (erythroid
      derived 2)-like 2 inducer sulforaphane ameliorated skin blistering in Krt14-null
      mice, correlating with induction of K17. To be therapeutically useful for
      epidermolysis bullosa simplex, topical broccoli sprout extract (BSE), enriched
      for sulforaphane, would ideally induce the expression of homologous keratins (eg,
      K6, K17, K16) in the basal layer of human epidermis without impacting expression
      of defective keratins (K5/K14). OBJECTIVE: The purpose of this 1-week,
      randomized, split-body, single-blinded, placebo-controlled trial was to assess
      the impact of BSE on keratin expression. METHODS: Five subjects (34-71 years old)
      applied BSE (500 nmol of sulforaphane/mL) or vehicle alone to the inner aspect of
      the arm daily. Expression of keratin, nuclear factor (erythroid-derived 2)-like
      2, and other markers was assessed using reverse transcription-polymerase chain
      reaction and indirect immunofluorescence. RESULTS: One subject (age 71 years) was
      excluded a posteriori because of poor tissue quality. Topical BSE activated
      nuclear factor (erythroid-derived 2)-like 2 and up-regulated K17 in the epidermis
      of all subjects, had variable effects on K16 and K6 expression, and did not alter
      expression of K14 or K5. LIMITATIONS: Small sample size is a limitation.
      CONCLUSION: BSE represents an attractive therapeutic candidate for K14-associated
      epidermolysis bullosa simplex.

PMID- 27889291
TI  - Acantholytic squamous cell carcinoma is usually associated with hair follicles,
      not acantholytic actinic keratosis, and is not "high risk": Diagnosis,
      management, and clinical outcomes in a series of 115 cases.
AB  - BACKGROUND: Acantholytic squamous cell carcinoma (aSCC) is regarded as a high
      risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic
      keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However,
      supporting evidence is limited. OBJECTIVE: We sought to document clinical
      features, histologic features, management, and outcomes in a series of aSCC
      cases. METHODS: Definitions of aSCC, aAK, and aSCC arising in association with
      aAK were applied to a consecutive series of aSCC cases. Clinical characteristics
      and outcomes were obtained from electronic medical records. RESULTS: Of 115 aSCC
      cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23%
      (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%)
      fulfilled strict histologic criteria for follicular SCC as previously defined,
      but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of
      follicular epithelium rather than epidermis. Clinical outcome (median follow-up,
      36 months) was available in 106 of 115 (92%). One patient experienced regional
      extension (parotid), and 1 patient experienced a local recurrence (nose). No
      disease-related metastases or deaths were documented. LIMITATIONS: This was a
      single-institution retrospective study from the United States. CONCLUSIONS: The
      presence of acantholysis in cutaneous SCC does not specifically confer aggressive
      behavior, a finding that may inform clinical practice guidelines.

PMID- 27889292
TI  - Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in
      psoriasis: Etanercept comparisons and integrated data.
AB  - BACKGROUND: Safety of biologics is important when treating patients with
      psoriasis. OBJECTIVE: We sought to determine the safety of ixekizumab in
      psoriasis. METHODS: Integrated safety data are presented from a 12-week induction
      period, a 12- to 60-week maintenance period, and from all ixekizumab-treated
      patients from 7 clinical trials. Exposure-adjusted incidence rates (IRs) per 100
      patient-years are reported. RESULTS: Overall, 4209 patients received ixekizumab
      (total exposure: 6480 patient-years). During the induction period, the IRs of
      patients experiencing 1 or more treatment-emergent adverse event (AE) were 251
      and 236 among ixekizumab- and etanercept-treated patients, respectively, and for
      serious AEs was 8.3 in both groups. During maintenance, for ixekizumab, the IRs
      of treatment-emergent AEs and serious AEs were 100.4 and 7.8, respectively. Among
      all ixekizumab-treated patients from 7 trials, the IR of Candida infections was
      2.5. The IRs of treatment-emergent AEs of special interest (including serious
      infections, malignancies, major adverse cardiovascular events) were comparable
      for ixekizumab and etanercept during the induction period. LIMITATIONS:
      Additional long-term data are required. CONCLUSION: Ixekizumab had an acceptable
      safety profile with no unexpected safety findings during ixekizumab maintenance
      in psoriasis.

PMID- 27889293
TI  - Stability behaviour of antiretroviral drugs and their combinations. 5:
      Characterization of novel degradation products of abacavir sulfate by mass and
      nuclear magnetic resonance spectrometry.
AB  - In the present study, degradation behaviour of abacavir sulfate was evaluated in
      solution and solid stress conditions. Solution state studies resulted in
      formation of eleven degradation products; of which two were also formed on solid
      stress. The same were separated by high performance liquid chromatography. They
      were characterized using liquid chromatography-high resolution mass spectrometry,
      liquid chromatography-multistage mass spectrometry and hydrogen/deuterium
      exchange mass spectrometry data. Additionally, seven degradation products were
      isolated and subjected to 1D and 2D nuclear magnetic resonance studies for their
      structural confirmation.

PMID- 27889294
TI  - Increasing the Detection of Familial Hypercholesterolaemia Using General Practice
      Electronic Databases.
AB  - BACKGROUND: Familial hypercholesterolaemia (FH) is a common autosomal co-dominant
      condition that causes premature cardiovascular disease. Awareness of FH is poor
      and only 10-15% of the affected population is identified. Electronic health
      records provide an opportunity to increase detection and awareness in general
      practice OBJECTIVE: To determine whether a simple electronic extraction tool can
      increase detection of FH in general practice. METHOD: An extraction tool applied
      to general practice electronic health records (EHR) to screen for FH, total
      cholesterol and low density lipoprotein cholesterol (LDL-c) levels in association
      with entered diagnostic criteria and demographic data in five general practices.
      RESULTS: Of 157,290 active patients examined, 0.7% (n=1081) had an LDL-c>5.0
      mmol/L representing 1 in 146 of active patients. An additional 0.8% (n=1276)
      patients were at possible risk of FH. Of those with an LDL-c>5.0 mmol/L 43.7% of
      patients had no record of being prescribed statins. Twenty patients (0.013%) had
      a clinical diagnosis of FH entered in the EHR. CONCLUSIONS: Patients at high risk
      of FH can be identified by a simple electronic screening method in general
      practice. Clinical data entry is variable in general practice. Targeted screening
      enables clinical assessment of patients at risk of cardiovascular disease and
      using the DLCNS will enable primary care to increase identification of FH.
      Approximately one in five patients extracted using this method, are likely to
      have phenotypically probable FH, making it a useful screening tool.

PMID- 27889295
TI  - Novel T7-like expression systems used for Halomonas.
AB  - To engineer non-model organisms, suitable genetic parts must be available.
      However, biological parts are often host strain sensitive. It is therefore
      necessary to develop genetic parts that are functional regardless of host
      strains. Here we report several novel phage-derived expression systems used for
      transcriptional control in non-model bacteria. Novel T7-like RNA polymerase
      promoter pairs were obtained by mining phage genomes, followed by in vivo
      characterization in non-model strains Halomonas spp TD01 and Pseudomonas
      entomophila. Three expression systems, namely, MmP1, VP4, and K1F, were developed
      displaying orthogonality (crosstalk<0.7%), tight regulation (3085-fold
      induction), and high efficiency (2.5-fold of Ptac) in Halomonas sp. TD01, a
      chassis strain with a high industrial value. The expression under the
      corresponding T7-like promoter libraries persisted with striking correlations (R2
      >0.94) between Escherichia coli and Halomonas sp. TD01, implying suitability of
      broad-host range. Three Halomonas TD strains were then constructed based upon
      these expression systems that enabled interchangeable and controllable gene
      expression. One of the strains termed Halomonas TD-MmP1 was used to express the
      cell-elongation cassette (minCD genes) and polyhydroxybutyrate (PHB) biosynthetic
      pathway, resulting in a 100-fold increase in cell lengths and high levels of PHB
      production (up to 92% of cell dry weight), respectively. We envision these T7
      like expression systems to benefit metabolic engineering in other non-model
      organisms.

PMID- 27889296
TI  - Donor and Recipient Views on Their Relationship in Living Kidney Donation:
      Thematic Synthesis of Qualitative Studies.
AB  - BACKGROUND: Many donors and recipients report an improved relationship after
      transplantation; however, tension, neglect, guilt, and proprietorial concern over
      the recipient can impede donor and recipient well-being and outcomes. We aimed to
      describe donor and recipient expectations and experiences of their relationship
      in the context of living kidney donation. STUDY DESIGN: Thematic synthesis of
      qualitative studies. SETTING & POPULATION: Living kidney donors and recipients.
      SEARCH STRATEGY & SOURCES: Electronic databases were searched to October 2015.
      ANALYTICAL APPROACH: Thematic synthesis. RESULTS: From 40 studies involving 1,440
      participants (889 donors and 551 recipients) from 13 countries, we identified 6
      themes. "Burden of obligation" described the recipient's perpetual sense of duty
      to demonstrate gratitude to the donor. "Earning acceptance" was the expectation
      that donation would restore relationships. "Developing a unique connection"
      reflected the inexplicable bond that donor-recipient dyads developed
      postdonation. "Desiring attention" was expressed by donors who wanted recognition
      for the act of donation and were envious and resentful of the attention the
      recipient received. "Retaining kidney ownership" reflected the donor's
      inclination to ensure that the recipient protected "their" kidney. "Enhancing
      social participation" encompassed relieving both the caregiver from the
      constraints of dialysis and the recipient from increased involvement and
      contribution in family life. LIMITATIONS: Non-English articles were excluded.
      CONCLUSIONS: Living kidney donation can strengthen donor-recipient relationships
      but may trigger or exacerbate unresolved angst, tension, jealousy, and
      resentment. Facilitating access to pre- and posttransplantation psychological
      support that addresses potential relationship changes may help donors and
      recipients better adjust to changes in the relationship dynamics, which in turn
      may contribute to improved psychosocial and transplantation outcomes following
      living kidney donation.

PMID- 27889297
TI  - Does an Aspirin a Day Keep the Doctor Away?

PMID- 27889298
TI  - Digging Deeper: Hidden Messages Beyond the Overall Prevalence of Diabetic Kidney
      Disease.

PMID- 27889299
TI  - Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a
      Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2
      Randomized Trial.
AB  - BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic
      risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved
      kidney function at 12 months postconversion versus those continuing CNI therapy,
      with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month
      follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI
      treated adult kidney transplant recipients with stable transplant function
      (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2). INTERVENTIONS:
      At 6 to 36 months posttransplantation, patients were randomly assigned to switch
      to belatacept-based immunosuppression (n=84) or continue CNI-based therapy
      (n=89). OUTCOMES: Safety was the primary outcome. eGFR, acute rejection,
      transplant loss, and death were also assessed. MEASUREMENTS: Treatment exposure
      adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan
      Meier analyses for efficacy. RESULTS: Serious adverse events occurred in 33 (39%)
      belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment
      exposure-adjusted incidence rates for serious infections (belatacept vs CNI,
      10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person
      years) were similar. More patients in the belatacept versus CNI group had any
      grade viral infections (14.60 vs 11.00 per 100 person-years). No
      posttransplantation lymphoproliferative disorder was reported. Belatacept-treated
      patients had a significantly greater estimated gain in mean eGFR (1.90 vs
      0.07mL/min/1.73m2 per year; P for time-by-treatment interaction effect = 0.01).
      The probability of acute rejection was not significantly different for belatacept
      (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of
      belatacept to the CNI group for time to death or transplant loss was 1.00 (95%
      CI, 0.14-7.07; P=0.9). LIMITATIONS: Exploratory post hoc analysis with a small
      sample size. CONCLUSIONS: Switching patients from a CNI to belatacept may
      represent a safe approach to immunosuppression and is being further explored in
      an ongoing phase 3b trial.

PMID- 27889300
TI  - Tofacitinib Versus Biologic Treatments in Patients With Active Rheumatoid
      Arthritis Who Have Had an Inadequate Response to Tumor Necrosis Factor
      Inhibitors: Results From a Network Meta-analysis.
AB  - PURPOSE: Tofacitinib is an oral Janus kinase inhibitor for the treatment of
      rheumatoid arthritis (RA). This analysis compared the efficacy and safety of
      tofacitinib with biologic disease-modifying antirheumatic drugs in patients with
      RA and a prior inadequate response (IR) to tumor necrosis factor inhibitors
      (TNFi). METHODS: A systematic literature review identified 5 randomized placebo
      controlled trials that evaluated tofacitinib or biologic disease-modifying
      antirheumatic drugs (bDMARDs) against placebo in patient populations with RA with
      a prior IR to TNFi. The definition of TNFi-IR varied across studies, and included
      patients with an IR or who had failed treatment with TNFi for any reason. A
      network meta-analysis was conducted comparing study data with regard to American
      College of Rheumatology response rates and Health Assessment Questionnaire
      Disability Index improvement at weeks 12 and 24, rates of treatment withdrawal
      due to all causes; adverse events (AEs) and lack of efficacy; and rates of AEs,
      serious AEs, and serious infections. FINDINGS: The 5 trials included a total of
      2136 patients. Tofacitinib 5 mg twice daily combined with methotrexate was found
      to have relative risk estimates of American College of Rheumatology responses and
      change from baseline in Health Assessment Questionnaire-Disability Index score
      comparable with abatacept, golimumab, rituximab, and tocilizumab combined with
      conventional synthetic disease-modifying antirheumatic drugs. Withdrawal rates
      from trials due to all causes and AEs were comparable between treatments, and
      tofacitinib had a lower rate of withdrawals due to lack of efficacy. Rates of AEs
      and HAQ-DI were comparable between tofacitinib, other active treatments, and
      placebo. No serious infections were reported with tofacitinib during the placebo
      controlled period (up to week 12) in this study population; rates of serious
      infection with other active treatments were generally low and similar to placebo.
      IMPLICATIONS: During a 24-week period, tofacitinib had efficacy and rates of AEs
      comparable with currently available bDMARDs in the treatment of patients with RA
      who had a prior IR to TNFi. ClinicalTrials.gov identifiers: ORAL Step,
      NCT00960440; ATTAIN, NCT00124982; GO-AFTER, NCT00299546; RADIATE, NCT00106522;
      REFLEX, NCT00462345.

PMID- 27889301
TI  - Glycemic Control and Weight Outcomes for Exenatide Once Weekly Versus Liraglutide
      in Patients with Type 2 Diabetes: A 1-Year Retrospective Cohort Analysis.
AB  - PURPOSE: Data comparing real-world effectiveness of the glucagon-like peptide-1
      receptor agonists (GLP-1RAs) exenatide once weekly (QW) and liraglutide in the
      treatment of type 2 diabetes (T2D) are limited. Furthermore, there is limited
      information on exenatide QW or liraglutide response by glycemic control and
      insulin use status. This study identifies 1-year glycosylated hemoglobin (HbA1c)
      and weight outcomes with exenatide QW and liraglutide in the real-world setting
      overall and in insulin-naive patients with uncontrolled T2D. METHODS: This
      retrospective cohort study using national electronic medical record data compared
      1-year HbA1c and weight outcomes in patients with T2D prescribed exenatide QW or
      liraglutide. Included patients were adults (>=18 years old) with T2D who were GLP
      1RA naive when newly prescribed exenatide QW or liraglutide between January 1,
      2012, and March 31, 2013 (index date). Outcomes were reported descriptively
      overall and in subsets of insulin-naive patients with baseline HbA1c >=7.0% or
      >=9.0%. Multivariable linear regression analyses were performed to estimate
      adjusted change in HbA1c and weight. FINDINGS: The study included 808 exenatide
      QW and 4333 liraglutide patients. Mean (SD) age was 57 (11) years in both groups.
      Mean baseline HbA1c was 8.3% (1.5%) in exenatide QW patients and 8.4% (1.6%) in
      liraglutide patients (P = 0.66); 16 (2%) of the exenatide QW and 1099 (25.4%) of
      the liraglutide patients were newly prescribed insulin on the index date (P <
      0.001). Adjusted mean HbA1c change at 1 year was -0.37% (95% CI, -0.53% to 
      0.21%) for exenatide QW and -0.37% (95% CI, -0.55% to -0.18%) for liraglutide.
      Adjusted HbA1c reduction was more pronounced in insulin-naive patients with
      baseline HbA1c >=7.0% (-0.71% and -0.80% for the exenatide QW and liraglutide
      patients, respectively, P > 0.05) and >=9.0% (-1.73% and -1.57% for exenatide QW
      and liraglutide patients, respectively, P > 0.05). Mean (adjusted) weight loss
      was -2.22 kg (95% CI, -3.06 to -1.37 kg) with exenatide QW and -2.21 kg (95% CI, 
      3.18 to -1.23 kg) with liraglutide. IMPLICATIONS: Exenatide QW and liraglutide
      lead to similar HbA1c and weight reductions at 1 year in the real-world setting.
      Greater HbA1c reductions occurred in insulin-naive patients with baseline HbA1c
      >=7.0%. Both agents are appropriate options for patients needing antidiabetes
      therapy to lower HbA1c while promoting weight loss.

PMID- 27889302
TI  - Preschool-Age Chinese Children's Weight Status: WHO Classification, Parent
      Ratings, Child/Family Characteristics.
AB  - PURPOSE: We aimed to compare preschool-age Chinese children's weight status based
      on the WHO guidelines with parental ratings on their children's body type, and
      child/family demographic characteristics. METHOD: The sample included 171
      preschool-age children (M=60.5months, SD=6.7; boys: 46.8%) randomly selected from
      23 classrooms. Based on BMIs from their height and weight from physical
      examinations, the children were divided into three groups using the 2006 WHO
      guidelines: underweight (n=46), normal weight (n=65), and overweight (n=60). Data
      on the parental ratings of children's current body type, ideal body type and
      child/family demographic characteristics were collected with surveys. RESULTS:
      Parents' accurately classified 91.1% of the underweight children, 52.3% of the
      normal weight children, and 61.7% of the overweight children. In terms of ideal
      body shape for their children, parents typically wanted their children to have
      normal weight or to remain underweight. Most of the child and family demographic
      characteristics were not different across children who were underweight, had
      normal weight, and were overweight. CONCLUSION: Because parents tended to
      underestimate their children's weight status, it is important to increase Chinese
      parents' knowledge on what constitutes healthy weight, as well as the potential
      harm of overweight status for children's development. Training healthcare
      providers in kindergartens and pediatric clinics to work with parents to
      recognize unhealthy weight status in children is valuable.

PMID- 27889303
TI  - PGLa-H tandem-repeat peptides active against multidrug resistant clinical
      bacterial isolates.
AB  - Antimicrobial peptides (AMPs) are promising candidates for new antibiotic classes
      but often display an unacceptably high toxicity towards human cells. A naturally
      produced C-terminal fragment of PGLa, named PGLa-H, has been reported to have a
      very low haemolytic activity while maintaining a moderate antibacterial activity.
      A sequential tandem repeat of this fragment, diPGLa-H, was designed, as well as
      an analogue with a Val to Gly substitution at a key position. These peptides
      showed markedly improved in vitro bacteriostatic and bactericidal activity
      against both reference strains and multidrug resistant clinical isolates of Gram
      negative and Gram-positive pathogens, with generally low toxicity for human cells
      as assessed by haemolysis, cell viability, and DNA damage assays. The glycine
      substitution analogue, kiadin, had a slightly better antibacterial activity and
      reduced haemolytic activity, which may correlate with an increased flexibility of
      its helical structure, as deduced using molecular dynamics simulations. These
      peptides may serve as useful lead compounds for developing anti-infective agents
      against resistant Gram-negative and Gram-positive species.

PMID- 27889305
TI  - Invasive prenatal diagnosis of fetal thalassemia.
AB  - Thalassemia is the most common monogenic inherited disease worldwide, affecting
      individuals originating from many countries to various extents. As the disease
      requires long-term care, prevention of the homozygous state presents a
      substantial global disease burden. The comprehensively preventive programs
      involve carrier detections, molecular diagnostics, genetic counseling, and
      prenatal diagnosis. Invasive prenatal diagnosis refers to obtaining fetal
      material by chorionic villus sampling (CVS) at the first trimester, and by
      amniocentesis or cordocentesis at the second trimester. Molecular diagnosis,
      which includes multiple techniques that are aimed at the detection of mutations
      in the alpha- or beta-globin genes, facilitates prenatal diagnosis and definitive
      diagnosis of the fetus. These are valuable procedures for couples at risk, so
      that they can be offered options to have healthy offspring. According to local
      practices and legislation, genetic counseling should accompany the invasive
      diagnostic procedures, DNA testing, and disclosure of the results. The most
      critical issue in any type of prenatal molecular testing is maternal cell
      contamination (MCC), especially when a fetus is found to inherit a particular
      mutation from the mother. The best practice is to perform MCC studies on all
      prenatal samples. The recent successful studies of fetal DNA in maternal plasma
      may allow future prenatal testing that is non-invasive for the fetus and result
      in significant reduction of invasive diagnostic procedures.

PMID- 27889304
TI  - Distinct membrane properties are differentially influenced by cardiolipin content
      and acyl chain composition in biomimetic membranes.
AB  - Cardiolipin (CL) has a critical role in maintaining mitochondrial inner membrane
      structure. In several conditions such as heart failure and aging, there is loss
      of CL content and remodeling of CL acyl chains, which are hypothesized to impair
      mitochondrial inner membrane biophysical organization. Therefore, this study
      discriminated how CL content and acyl chain composition influenced select
      properties of simple and complex mitochondrial mimicking model membranes. We
      focused on monolayer excess area/molecule (a measure of lipid miscibility),
      bilayer phase transitions, and microdomain organization. In monolayer compression
      studies, loss of tetralinoleoyl [(18:2)4] CL content decreased the excess
      area/molecule. Replacement of (18:2)4CL acyl chains with tetraoleoyl [(18:1)4] CL
      or tetradocosahexaenoyl [(22:6)4] CL generally had little influence on monolayer
      excess area/molecule; in contrast, replacement of (18:2)4CL acyl chains with
      tetramyristoyl [(14:0)4] CL increased monolayer excess area/molecule. In
      bilayers, calorimetric studies showed that substitution of (18:2)4CL with
      (18:1)4CL or (22:6)4CL lowered the phase transition temperature of
      phosphatidylcholine vesicles whereas (14:0)4CL had no effect. Finally,
      quantitative imaging of giant unilamellar vesicles revealed differential effects
      of CL content and acyl chain composition on microdomain organization, visualized
      with the fluorescent probe Texas Red DHPE. Notably, microdomain areas were
      decreased by differing magnitudes upon lowering of (18:2)4CL content and
      substitution of (18:2)4CL with (14:0)4CL or (22:6)4CL. Conversely, exchanging
      (18:2)4CL with (18:1)4CL increased microdomain area. Altogether, these data
      demonstrate that CL content and fatty acyl composition differentially target
      membrane physical properties, which has implications for understanding how CL
      regulates mitochondrial activity and the design of CL-specific therapeutics.

PMID- 27889306
TI  - Return to Sporting Activity After Total Hip Arthroplasty-A Survey of Members of
      the British Hip Society.
AB  - BACKGROUND: Total hip arthroplasty is increasingly performed in younger, more
      active patients. Thirty-five percent of patients are involved in sports
      preoperatively, and a desire to return to sporting activity is now a major
      expectation. Sporting activity potentially risks premature failure of the
      implant, and there is no consensus or guidelines among British or European
      surgeons performing total hip arthroplasty in sporting patients. METHODS: The
      current practice of British Hip Society members was explored through a Web-based
      survey. Of the 260 members surveyed, 109 responded. RESULTS: The majority of
      respondents (33%) would perform uncemented, 29.1% would perform hybrid, 15.5%
      would perform fully cemented, and 11.7% would perform a resurfacing hip
      arthroplasty for sporting patients. The preferred approach is the standard
      posterior (68.9%) and preferred bearing couples are ceramic-on-ceramic (39.8%)
      and ceramic-on-polyethylene (36.9%). Half of respondents would opt for a femoral
      head smaller than 36 mm, whereas 22.3% would use a head 36 mm or larger. A third
      would allow patients to return to sports between 6 and 12 weeks after surgery,
      whereas 43.7% advise patients to wait until 3 months postoperatively. All
      respondents allow patients to return to low-impact activities, but significant
      caution is exercised with regard to taking part in high-impact activities.
      CONCLUSION: We report the practice of a specialist group of hip surgeons, the
      majority of which consider themselves young adult hip specialists. We believe
      that these data may be of use to help inform the practice of our colleagues when
      performing arthroplasty in sporting patients and may serve to inform future
      consensus guidelines.

PMID- 27889307
TI  - Efficacy of a Single Dose and an Additional Dose of Tranexamic Acid in Reduction
      of Blood Loss in Total Knee Arthroplasty.
AB  - BACKGROUND: This study aimed at evaluating the efficacy and safety of different
      regimens with a single dose and an additional postoperative dose of tranexamic
      acid (TA) in reducing blood loss in total knee arthroplasty (TKA). METHODS: A
      total of 180 patients who were scheduled to undergo primary unilateral TKA in our
      level I trauma center were recorded and divided into groups A, B, C, and D
      randomly. Preoperative dose, an additional postoperative dose, and 2
      postoperative additional doses of TA were infused intravenously in groups A (30
      mg/kg), B (15 mg/kg), and C (10 mg/kg), respectively, and TA was not infused in
      group D. Blood loss (intraoperative, postoperative, and total blood loss), blood
      transfusion rate and volume, hemoglobin level, and incidence of deep vein
      thrombosis were analyzed. RESULTS: The total blood loss and postoperative blood
      loss were significantly lower in groups B and C without any difference between
      them. As for intraoperative blood loss, there was no significant difference
      between groups A and B and between groups B and C with superior efficacy than
      group D. CONCLUSION: With the same total dose of TA, the preoperative dose and an
      additional dose of TA were superior to a single preoperative dose of TA in
      reducing blood loss in TKA. Besides, 1 additional dose was comparable to 2
      additional doses of TA in reducing blood loss.

PMID- 27889308
TI  - Letter to the Editor on "Bilateral Total Hip Arthroplasty: 1-Stage or 2-Stage? A
      Meta-Analysis".

PMID- 27889309
TI  - Response to Letter to the Editor on "Bilateral Total Hip Arthroplasty: One-Stage
      or Two-Stage? A Meta-Analysis".

PMID- 27889310
TI  - Barriers for transradial coronary angiography and interventions in 2016.

PMID- 27889311
TI  - Structural evaluation of a nanobody targeting complement receptor Vsig4 and its
      cross reactivity.
AB  - Vsig4 is a recently identified immune regulatory protein related to the B7 family
      with dual functionality: a negative regulator of T cell activation and a receptor
      for the complement components C3b and C3c. Here we present a structural
      evaluation of a nanobody, Nb119, against the extracellular IgV domain protein of
      both mouse and human recombinant Vsig4, which have a high degree of sequence
      identity. Although mouse and human Vsig4 bind to Nb119 with a 250 times
      difference in dissociation constants, the interaction results in a highly
      identical assembly with a RMSD of 0.4A. The molecular determinants for Vsig4
      recognition and cross reactivity unveiled by the atomic structure of Nb119 in
      complex with mVsig4 and hVsig4 afford new insights useful for the further
      optimization of the nanobody for potential use in humans. Additionally,
      structural analysis of the Vsig4-Nb119 complexes indicates that Nb119 occupies
      the interface on Vsig4 recognized by the macroglobulin-like domains MG4 and MG5
      of C3b. Thus an affinity-improved Nb119 may have the potential to influence the
      activation of both T cells and complement.

PMID- 27889312
TI  - Efficacy, safety, and tolerability of lacosamide monotherapy versus controlled
      release carbamazepine in patients with newly diagnosed epilepsy: a phase 3,
      randomised, double-blind, non-inferiority trial.
AB  - BACKGROUND: Further options for monotherapy are needed to treat newly diagnosed
      epilepsy in adults. We assessed the efficacy, safety, and tolerability of
      lacosamide as a first-line monotherapy option for these patients. METHODS: In
      this phase 3, randomised, double-blind, non-inferiority trial, patients from 185
      epilepsy or general neurology centres in Europe, North America, and the Asia
      Pacific region, aged 16 years or older and with newly diagnosed epilepsy were
      randomly assigned in a 1:1 ratio, via a computer-generated code, to receive
      lacosamide monotherapy or controlled-release carbamazepine (carbamazepine-CR)
      twice daily. Patients, investigators, and trial personnel were masked to
      treatment allocation. From starting doses of 100 mg/day lacosamide or 200 mg/day
      carbamazepine-CR, uptitration to the first target level of 200 mg/day and 400
      mg/day, respectively, took place over 2 weeks. After a 1-week stabilisation
      period, patients entered a 6-month assessment period. If a seizure occurred, the
      dose was titrated to the next target level (400 or 600 mg/day for lacosamide and
      800 or 1200 mg/day for carbamazepine-CR) over 2 weeks with a 1-week stabilisation
      period, and the 6-month assessment period began again. Patients who completed 6
      months of treatment and remained seizure-free entered a 6-month maintenance
      period on the same dose. The primary efficacy outcome was the proportion of
      patients remaining free from seizures for 6 consecutive months after
      stabilisation at the last assessed dose. The predefined non-inferiority criteria
      were -12% absolute and -20% relative difference between treatment groups. This
      trial is registered with ClinicalTrials.gov, number NCT01243177. FINDINGS: The
      trial was done between April 27, 2011, and Aug 7, 2015. 888 patients were
      randomly assigned treatment. 444 patients taking lacosamide and 442 taking
      carbamazepine-CR were included in the full analysis set (took at least one dose
      of study treatment), and 408 and 397, respectively, were included in the per
      protocol set. In the full analysis set, 327 (74%) patients in the lacosamide
      group and 308 (70%) in the carbamazepine-CR group completed 6 months of treatment
      without seizures. The proportion of patients in the full analysis set predicted
      by the Kaplan-Meier method to be seizure-free at 6 months was 90% taking
      lacosamide and 91% taking carbamazepine-CR (absolute treatment-difference: -1.3%,
      95% CI -5.5 to 2.8 relative treatment difference: -6.0%). Kaplan-Meier estimates
      results were similar in the per-protocol set (92% and 93%; -1.3%, -5.3 to 2.7; 
      5.7%). Treatment-emergent adverse events were reported in 328 (74%) patients
      receiving lacosamide and 332 (75%) receiving carbamazepine-CR. 32 (7%) patients
      taking lacosamide and 43 (10%) taking carbamazepine-CR had serious treatment
      emergent adverse events, and 47 (11%) and 69 (16%), respectively, had treatment
      emergent adverse events that led to withdrawal. INTERPRETATION: Treatment with
      lacosamide met the predefined non-inferiority criteria when compared with
      carbamazepine-CR. Therefore, it might be useful as first-line monotherapy for
      adults with newly diagnosed epilepsy. FUNDING: UCB Pharma.

PMID- 27889313
TI  - Lacosamide monotherapy for newly diagnosed epilepsy.

PMID- 27889315
TI  - School-Based Obesity-Prevention Policies and Practices and Weight-Control
      Behaviors among Adolescents.
AB  - BACKGROUND: The promotion of healthy eating and physical activity within school
      settings is an important component of population-based strategies to prevent
      obesity; however, adolescents may be vulnerable to weight-related messages, as
      rapid development during this life stage often leads to preoccupation with body
      size and shape. OBJECTIVE: This study examines secular trends in secondary school
      curricula topics relevant to the prevention of unhealthy weight-control
      behaviors; describes cross-sectional associations between weight-related
      curricula content and students' use of weight-control behaviors; and assesses
      whether implementation of school-based obesity-prevention policies/practices is
      longitudinally related to students' weight-control behaviors. DESIGN: The
      Minnesota School Health Profiles and Minnesota Student Survey (grades 9 and 12)
      data were used along with National Center for Education Statistics data to
      examine secular trends, cross-sectional associations (n=141 schools), and
      longitudinal associations (n=42 schools). MAIN OUTCOME MEASURES: Students self
      reported their height and weight along with past-year use of healthy (eg,
      exercise), unhealthy (eg, fasting), and extreme (eg, use laxatives) weight
      control behaviors. STATISTICAL ANALYSES PERFORMED: Descriptive statistics,
      generalized estimating equations, and generalized linear regression models
      accounting for school-level demographics. RESULTS: There was no observable
      pattern during the years 2008 to 2014 in the mean number of curricula topics
      addressing unhealthy weight-control behaviors, despite an increase in the
      prevalence of curricula addressing acceptance of body-size differences. Including
      three vs fewer weight-control topics and specifically including the topic of
      eating disorders in the curricula was related to a lower school-level percent of
      students using any extreme weight-control behaviors. In contrast, an overall
      measure of implementing school-based obesity-prevention policies/practices (eg,
      prohibited advertising) was unrelated to use of unhealthy or extreme behaviors.
      CONCLUSIONS: Results suggest obesity-prevention policies/practices do not have
      unintended consequences for student weight-control behaviors and support the
      importance of school-based health education as part of efforts to prevent
      unhealthy behaviors.

PMID- 27889314
TI  - Dietary Patterns during Adulthood among Lesbian, Bisexual, and Heterosexual Women
      in the Nurses' Health Study II.
AB  - BACKGROUND: Lesbian and bisexual women are at greater risk of being obese than
      heterosexual women; however, there is little research on dietary intake among
      lesbian and bisexual women. OBJECTIVE: This study estimated differences in
      dietary quality and intake during adulthood comparing heterosexual women to
      lesbian and bisexual women. DESIGN: Biennial mailed questionnaires were used to
      collect data from a cohort between 1991 and 2011. Heterosexual-identified women
      were the reference group. PARTICIPANTS/SETTING: More than 100,000 female
      registered nurses in the United States, aged 24 to 44 years, were recruited in
      1989 to participate in the Nurses' Health Study II. More than 90% of the original
      sample are currently active in the study. About 1.3% identified as lesbian or
      bisexual. MAIN OUTCOME MEASURES: Dietary measures were calculated from a 133-item
      food frequency questionnaire administered every 4 years. Measures included diet
      quality (Alternative Healthy Eating Index-2010 and Dietary Approaches to Stop
      Hypertension); calorie, fat, and fiber intake; and glycemic load and index.
      STATISTICAL ANALYSES: Multivariable adjusted repeated measures linear regression
      models were fit. RESULTS: On average, lesbian and bisexual women reported better
      diet quality (P<0.001) and diets lower in glycemic index (P<0.001) than
      heterosexual women. In the whole cohort, diet quality scores increased as
      participants aged, and were lower among women living in rural compared to urban
      regions. Comparisons in dietary intake across sexual orientation groups were
      generally similar across age and rurality status. However, differences between
      lesbian and heterosexual women in Alternative Healthy Eating Index-2010 were
      larger during younger compared to older ages, suggesting that diet quality
      estimates among sexual orientation groups converged as women aged. CONCLUSIONS:
      Lesbian and bisexual women reported higher diet quality than heterosexuals. More
      research examining how diet affects risk for chronic conditions, such as
      diabetes, among sexual minorities is needed. Physical activity, sedentary
      behavior, disordered eating behaviors, and psychosocial and minority stress
      should be explored as potential contributors to higher rates of obesity among
      sexual minority women.

PMID- 27889316
TI  - Antimony content of inorganic gunshot residue (IGSR) produced by 0.22 caliber
      rimfire ammunition having free-antimony primer.
AB  - In a recent paper published in Forensic Science International (FSI), Lucas et al.
      (2016) claimed that muzzle discharge of 0.22 caliber rimfire ammunition is more
      likely to incorporate particles from the bullet surface than those retained on
      the firearm and that characteristic particles containing Pb, Ba and Sb formed
      from known Sb-free primers are likely to be more prevalent in muzzle discharge.
      It seems that this claim is not based on sufficient experimental results.

PMID- 27889317
TI  - The p53 Family Coordinates Wnt and Nodal Inputs in Mesendodermal Differentiation
      of Embryonic Stem Cells.
AB  - In this study, we outline a regulatory network that involves the p53 tumor
      suppressor family and the Wnt pathway acting together with the TGF-beta pathway
      in mesendodermal differentiation of mouse and human embryonic stem cells.
      Knockout of all three members, p53, p63, and p73, shows that the p53 family is
      essential for mesendoderm specification during exit from pluripotency in embryos
      and in culture. Wnt3 and its receptor Fzd1 are direct p53 family target genes in
      this context, and induction of Wnt signaling by p53 is critical for activation of
      mesendodermal differentiation genes. Globally, Wnt3-activated Tcf3 and nodal
      activated Smad2/3 transcription factors depend on each other for co-occupancy of
      target enhancers associated with key differentiation loci. Our results therefore
      highlight an unanticipated role for p53 family proteins in a regulatory network
      that integrates essential Wnt-Tcf and nodal-Smad inputs in a selective and
      interdependent way to drive mesendodermal differentiation of pluripotent cells.

PMID- 27889318
TI  - Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into
      Functionally Integrated Neurons in the Neonatal Cortex.
AB  - Whether new neurons are added in the postnatal cerebral cortex is still debated.
      Here, we report that the meninges of perinatal mice contain a population of
      neurogenic progenitors formed during embryonic development that migrate to the
      caudal cortex and differentiate into Satb2+ neurons in cortical layers II-IV. The
      resulting neurons are electrically functional and integrated into local
      microcircuits. Single-cell RNA sequencing identified meningeal cells with
      distinct transcriptome signatures characteristic of (1) neurogenic radial glia
      like cells (resembling neural stem cells in the SVZ), (2) neuronal cells, and (3)
      a cell type with an intermediate phenotype, possibly representing radial glia
      like meningeal cells differentiating to neuronal cells. Thus, we have identified
      a pool of embryonically derived radial glia-like cells present in the meninges
      that migrate and differentiate into functional neurons in the neonatal cerebral
      cortex.

PMID- 27889319
TI  - Cell-Type-Specific Chromatin States Differentially Prime Squamous Cell Carcinoma
      Tumor-Initiating Cells for Epithelial to Mesenchymal Transition.
AB  - Epithelial to mesenchymal transition (EMT) in cancer cells has been associated
      with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT
      while others do not, which may reflect intrinsic properties of their cell of
      origin. However, this possibility is largely unexplored. By targeting the same
      oncogenic mutations to discrete skin compartments, we show that cell-type
      specific chromatin and transcriptional states differentially prime tumors to EMT.
      Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are
      generally well differentiated, while hair follicle (HF) stem cell-derived SCCs
      frequently exhibit EMT, efficiently form secondary tumors, and possess increased
      metastatic potential. Transcriptional and epigenomic profiling revealed that IFE
      and HF tumor-initiating cells possess distinct chromatin landscapes and gene
      regulatory networks associated with tumorigenesis and EMT that correlate with
      accessibility of key epithelial and EMT transcription factor binding sites. These
      findings highlight the importance of chromatin states and transcriptional priming
      in dictating tumor phenotypes and EMT.

PMID- 27889320
TI  - Optimizing effectivity of tranexamic acid in bilateral knee arthroplasty - A
      prospective randomized controlled study.
AB  - INTRODUCTION: Tranexamic acid (TEA) is used in reducing surgical blood loss.
      Literature shows no optimal regimen recommended for Bilateral Total Knee
      Arthroplasty (TKA). We evaluated three TEA regimens differing in dosage, timing
      and mode of administration in bilateral TKA to identify the most effective
      regimen to reduce blood loss. METHODS: We prospectively studied three TEA
      regimens (25 patients each) as follows: (1) two intraoperative, intravenous doses
      (IOIO), (2) two intraoperative local applications (LALA), and (3) one
      preoperative plus two intraoperative, intravenous doses (POIOIO). Two independent
      parameters of drain loss and total blood loss, calculated by the hemoglobin
      balance method were statistically evaluated. RESULTS: Mean drain loss was least
      (412.9ml) in the POIOIO group, greatest (607.2ml) in the IOIO group and LALA
      group in between (579.4ml), with a statistically significant difference among
      them (p=0.0022). On paired evaluation, the drain loss in the POIOIO group was
      significantly less as compared to the other two groups, whereas the difference
      between IOIO and LALA was not significant. Mean total blood loss was least in the
      POIOIO group (1207ml) and greatest in LALA group (1270ml). The difference among
      the groups was not statistically significant (p=0.80). There was no incidence of
      any thromboembolic phenomenon. On correlation with our study on Most Effective
      Regimen in Unilateral TKA, both results were found to substantiate each other.

PMID- 27889321
TI  - Rapid antigen detection test for respiratory syncytial virus diagnosis as a
      diagnostic tool.
AB  - OBJECTIVE: The aim of this study was to evaluate the QuickVue(r) RSV Test Kit
      (QUIDEL Corp, CA, USA) as a screening tool for respiratory syncytial virus in
      children with acute respiratory disease in comparison with the indirect
      immunofluorescence assay as gold standard. In Brazil, rapid antigen detection
      tests for respiratory syncytial virus are not routinely utilized as a diagnostic
      tool, except for the diagnosis of dengue and influenza. METHODS: The authors
      retrospectively analyzed 486 nasopharyngeal aspirate samples from children under
      age 5 with acute respiratory infection, between December 2013 and August 2014,
      the samples were analyzed by indirect immunofluorescence assay and QuickVue(r)
      RSV Test kit. Samples with discordant results were analyzed by real time PCR and
      nucleotide sequencing. RESULTS: From 313 positive samples by immunofluorescence
      assays, 282 (90%) were also positive by the rapid antigen detection test, two
      were positive only by rapid antigen detection test, 33 were positive only by
      immunofluorescence assays, and 171 were positive by both methods. The 35 samples
      with discordant results were analyzed by real time PCR; the two samples positive
      only by rapid antigen detection test and the five positive only by
      immunofluorescence assays were also positive by real time PCR. There was no
      relation between the negativity by QuickVue(r) RSV Test and viral load or
      specific strain. The QuickVue(r) RSV Test showed sensitivity of 90%, specificity
      of 98.8%, predictive positive value of 99.3%, and negative predictive value of
      94.6%, with accuracy of 93.2% and agreement kappa index of 0.85 in comparison to
      immunofluorescence assay. CONCLUSIONS: This study demonstrated that the
      QuickVue(r) RSV Test Kit can be effective in early detection of Respiratory
      syncytial virus in nasopharyngeal aspirate and is reliable for use as a
      diagnostic tool in pediatrics.

PMID- 27889322
TI  - Landmark reading alterations in patients with gastro-oesophageal reflux symptoms
      undergoing diagnostic gastroscopy.
AB  - BACKGROUND AND STUDY AIMS: There is still a debate about the exact measurement of
      the oesophagogastric junction and the diaphragmatic hiatus among clinicians. The
      aim of this study was to investigate the differences between landmark readings of
      gastroscopy on intubation and extubation, and to correlate these readings with a
      gastro-oesophageal reflux questionnaire. PATIENTS AND METHODS: 116 cases who
      underwent diagnostic gastroscopy between January 2013 and June 2013 were included
      in this study. Landmark measurements were noted while withdrawing the endoscope
      and were also evaluated after the gastric air was fully emptied. We first used a
      frequency scale for the gastro-oesophageal reflux disease symptoms (FSSG)
      questionnaire in order to investigate dysmotility and acid reflux symptoms in the
      study population and correlated the FSSG questionnaire with intubation and
      extubation measurements at endoscopic examination. RESULTS: Mean age of included
      subjects was 49.41+/-17.7 (19-82) years. Males and females were equally
      represented. On FSSG scores, the total dysmotility score was 7.99+/-5.06 and the
      total score was 15.18+/-10.11. The difference between intubation and extubation
      measurements ranged from -3cm to +2cm (mean: -0.4). When an FSSG score of 30 was
      accepted as a cut-off value, we detected a significant difference between the
      measurements (p<0.05; t: 0.048). CONCLUSION: Accuracy of landmark measurements
      during gastroscopy is clearly affected from insertion or withdrawal of the
      endoscope. When differences in measurements between insertion and withdrawal were
      evident, comparable with the FSSG scores, the results became significantly
      different. In conclusion, according to FSSG scores, these measurements should be
      performed at the end of the endoscopy.

PMID- 27889323
TI  - [Primary immunodeficiency and autoimmunity].
AB  - Many evidences highlight that immunodeficiency and autoimmunity are two sides of
      a same coin. Primary immune deficiencies (PIDs), which are rare mono- or
      multigenic defects of innate or adaptative immunity, frequently associate with
      autoimmunity. Analyses of single-gene defects in immune pathways of families with
      PIDs, by new tools of molecular biology (next genome sequencing technologies),
      allowed a better understanding of the ways that could both drive immune defect
      with immune deficiency and autoimmunity. Moreover, genes implicated in rare
      single-gene defects are now known to be also involved in polygenic conventional
      autoimmune diseases. Here, we describe the main autoimmune symptoms occurring in
      PIDs and the underlying mechanisms that lead to autoimmunity in immunodeficiency.
      We review the links between autoimmunity and immunodeficiency and purpose some
      principles of care for patients with PIDs and autoimmunity.

PMID- 27889324
TI  - [An abnormal tongue].

PMID- 27889325
TI  - [Langerhans cell histiocytosis and Erdheim-Chester disease, a continuity?]
AB  - INTRODUCTION: Erdheim-Chester disease and langerhans cell histiocytosis are two
      rare diseases separate on clinical, radiological and histological aspects.
      However, several cases involving both entities have been described. OBSERVATION:
      A 70-year-old man had a central diabetes insipidus, xanthelasmas, retroperitoneal
      fibrosis and osteosclerosis of the legs suggestive of Erdheim-Chester disease.
      Bone biopsy showed langerhans cell histiocytosis CD1a positive with the presence
      of BRAF V600E mutation. The patient was treated with vemurafenib with a good
      clinical course. CONCLUSION: The literature review finds forty observations
      linking the two diseases that may suggest a pathophysiological link, especially
      with the hematopoietic myeloid stem cell CD34+. The term inflammatory myeloid
      neoplasm was advanced.

PMID- 27889326
TI  - [Inventory of training of internal medicine in France: Results of a national
      survey].
AB  - OBJECTIVE: To make an inventory of training of Internal Medicine in France.
      METHOD: This study was conducted between May and September 2015 with coordinators
      (interviews of 45minutes) of local Internal Medicine training and fellows (online
      questionnaire). RESULTS: All coordinators (n=28) responded to the interviews.
      Local training of Internal Medicine exists in 86% of regions (3.1+/
      3.1hours/month) and an interregional training in all interregions (34.7+/
      13.9hours/year). When excluding Ile-de-France, no correlation between the number
      of teachers and the amount of lessons was noted (P=0.61). Of the 550 fellows in
      Internal Medicine in 2014-2015, 223 (41%) responded to the online questionnaire.
      Mean level was 5.5+/-2.7 semesters. The rate of satisfaction (1=very dissatisfied
      and 5=very satisfied) was 3.0+/-1.0 and 3.8+/-0.8 for regional and interregional
      teaching, respectively (P<0.0001). Regional teaching satisfaction was correlated
      with the perceived expanse of diseases covered into the program (P<0.0001). In
      addition, 89% of fellows wish to evaluate themselves online, 66% wish to have a
      practical evaluation at the bedside and 70% in simulation centers. Finally, 91%
      of fellows support the establishment of a national program for the training of
      Internal Medicine. CONCLUSION: This survey states for the first time an inventory
      of training of Internal Medicine dedicated to fellows in France. This report
      highlights that fellows wish to have a national program, be further evaluated and
      have access to more interactive approach of teaching.

PMID- 27889327
TI  - Epigenetics in non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD), a common hepatic disorder ranging from
      simple steatosis through steatohepatitis to fibrosis and cirrhosis, is an
      emerging health concern. NAFLD is a pathologic condition characterized by the
      buildup of extra fat in liver cells that is not caused by alcohol consumption.
      Excess hepatic fat accumulation results from increased delivery of triglycerides
      (TG) to the liver or conversion of surplus carbohydrates to TG. Importantly, a
      subgroup of NAFLD results in hepatocellular injury and inflammation, which is
      referred to as non-alcoholic steatohepatitis (NASH), and may progress to
      irreversible cirrhosis and hepatocellular carcinoma (HCC). NAFLD shares, in part,
      the common pathogenesis of metabolic syndrome including obesity, hyperlipidemia,
      insulin resistance, mitochondrial damage, oxidative stress response, and the
      release of inflammatory cytokines. Epigenetics, an inheritable phenomenon that
      affects gene expression without altering the DNA sequence, provides a new
      perspective on the pathogenesis of NAFLD. Reversible epigenetic changes take
      place at the transcriptional level and provide a phenotypic connection between
      the host and environment. An accumulating body of evidence suggests the
      importance of epigenetic roles in NAFLD, which in turn can be identified as
      potential therapeutic targets and non-invasive biomarkers of NAFLD. It is
      anticipated that the epigenetic modifiers in NAFLD may provide novel molecular
      indicators that can determine not only the initial risk but also the disease
      progression and prognosis. In the present review, we update the roles of
      epigenetics as pathologic mechanisms, therapeutic targets and biomarkers in
      NAFLD.

PMID- 27889328
TI  - Multiple Spontaneous Coronary Artery Dissections: An Uncommon Cause of Acute
      Coronary Syndrome in a Syrian Refugee.
AB  - Spontaneous coronary artery dissection is an uncommon nonatherosclerotic cause of
      acute coronary syndrome. It usually occurs in young women and is often associated
      with fibromuscular dysplasia, connective tissue diseases, and pregnancy or
      postpartum states. We present a case of a Syrian woman with a history of grand
      multiparity and recent miscarriage who presented with non-ST-elevation myocardial
      infarction and was found to have multivessel spontaneous coronary artery
      dissection and severe left ventricular dysfunction.

PMID- 27889330
TI  - Use of biologics to treat acute exacerbations and manage disease in asthma, COPD
      and IPF.
AB  - A common feature of chronic respiratory disease is the progressive decline in
      lung function. The decline can be indolent, or it can be accelerated by acute
      exacerbations, whereby the patient experiences a pronounced worsening of disease
      symptoms. Moreover, acute exacerbations may also be a marker of insufficient
      disease management. The underlying cause of an acute exacerbation can be due to
      insults such as pathogens or environmental pollutants, or the cause can be
      unknown. For each acute exacerbation, the patient may require medical
      intervention such as rescue medication, or in more severe cases, hospitalization
      and ventilation and have an increased risk of death. Biologics, such as
      monoclonal antibodies, are being developed for chronic respiratory diseases
      including asthma, COPD and IPF. This therapeutic approach is particularly well
      suited for chronic use based on the route and frequency of delivery and
      importantly, the potential for disease modification. In recent clinical trials,
      the frequency of acute exacerbation has often been included as an endpoint, to
      help determine whether the investigational agent is impacting disease. Therefore
      the significance of acute exacerbations in driving disease, and their potential
      as a marker of disease activity and progression, has recently received much
      attention. There is also now a need to standardize the definition of an acute
      exacerbation in specific disease settings, particularly as this endpoint is
      increasingly used in clinical trials to also assess therapeutic efficacy.
      Moreover, specifically targeting exacerbations may offer a new therapeutic
      approach for several chronic respiratory diseases.

PMID- 27889329
TI  - Perivascular cells and tissue engineering: Current applications and untapped
      potential.
AB  - The recent development of tissue engineering provides exciting new perspectives
      for the replacement of failing organs and the repair of damaged tissues.
      Perivascular cells, including vascular smooth muscle cells, pericytes and other
      tissue specific populations residing around blood vessels, have been isolated
      from many organs and are known to participate to the in situ repair process and
      angiogenesis. Their potential has been harnessed for cell therapy of numerous
      pathologies; however, in this Review we will discuss the potential of
      perivascular cells in the development of tissue engineering solutions for
      healthcare. We will examine their application in the engineering of vascular
      grafts, cardiac patches and bone substitutes as well as other tissue engineering
      applications and we will focus on their extensive use in the vascularization of
      engineered constructs. Additionally, we will discuss the emerging potential of
      human pericytes for the development of efficient, vascularized and non
      immunogenic engineered constructs.

PMID- 27889331
TI  - Portulaca oleracea L. prevents lipopolysaccharide-induced passive avoidance
      learning and memory and TNF-alpha impairments in hippocampus of rat.
AB  - There is a growing body of evidence that neuroinflammation can impair memory. It
      has been indicated that Portulaca oleracea Linn. (POL), possess anti-inflammatory
      activity and might improve memory disruption caused by inflammation. In this
      study the effect of pre-treatment with the hydro-alcoholic extract of POL on
      memory retrieval investigated in lipopolysaccharide (LPS) treated rats. Male
      Wistar rats (200-220g) received either a control diet or a diet containing of POL
      (400mg/kg, p.o.) for 14days. Then, they received injections of either saline or
      LPS (1mg/kg, i.p.). In all the experimental groups, 4h following the last
      injection, passive avoidance learning (PAL) and memory test was performed. The
      retention test was done 24h after the training and then the animals were
      sacrificed. Hippocampal TNF-alpha levels measured using ELISA as one criteria of
      LPS-induced neuroinflammation. The results indicated that LPS significantly
      impaired PAL and memory and increased TNF-alpha levels in hippocampus tissue. Pre
      treatment with POL improved memory in control rats and prevented memory and TNF
      alpha deterioration in LPS treated rats. Taken together, the results of this
      study suggest that the hydro-alcoholic extract of POL may improve memory deficits
      in LPS treated rats, possibly via inhibition of TNF-alpha and anti-inflammatory
      activity.

PMID- 27889332
TI  - Effect of an aerobic exercise intervention on cardiac autonomic regulation: A
      worksite RCT among cleaners.
AB  - OBJECTIVE: The aim of this randomized controlled trial (RCT) was to determine
      whether aerobic exercise during work hours affects cardiac autonomic regulation
      in cleaners characterized by high levels of occupational physical activity and
      poor cardiorespiratory fitness. METHOD: Eligible cleaners (n=116) were randomized
      to an aerobic exercise group (n=59) or a reference group (n=57) with lectures.
      The intervention group received two 30-min sessions per week of supervised
      aerobic exercise over 4months. Diurnal measurements of heart rate variability
      (HRV) and physical activity (accelerometry) were obtained at baseline and at 4
      month follow-up. Time and frequency domain indices of HRV were derived during
      work, leisure time and sleep to evaluate cardiac autonomic regulation. Linear
      mixed models were used to determine the effect of the intervention on HRV
      indices, with adjustment for age, gender and daily use of antihypertensive and/or
      heart medication. RESULTS: Compared with the reference group, the exercise group
      increased all HRV indices apart from a reduction in LF/HF ratio from baseline to
      follow-up both during work (p<0.05) and leisure (p<0.05). In contrast, during
      sleep, the HRV indices tended to decrease in the exercise group compared with the
      reference group from baseline to follow-up, being significant for the HF spectral
      component (p=0.03). CONCLUSION: Among cleaners, a worksite aerobic exercise
      intervention improved cardiac autonomic regulation during work and leisure, but
      not during sleep. The health effect of this contrasting change in autonomic
      regulation needs further investigation.

PMID- 27889333
TI  - Magnetoencephalography (MEG): Past, current and future perspectives for improved
      differentiation and treatment of epilepsies.
AB  - In addition to visual analysis digital computerized recording of electrical and
      magnetic fields by using EEG and MEG opened a new window for research concerning
      improved understanding of pathophysiology, diagnosis and treatment of epilepsies.
      In the last 25 years MEG was used more and more in clinical studies concerning
      localization of focal epileptic activity, functional cortex and network analysis.
      Simultaneous MEG/EEG recording and analysis offer the use of complimentary
      information increasing the sensitivity for tracing primary epileptic activity.
      Combined MEG/Stereo-EEG recordings showed that MEG noninvasively identified
      regional interictal networks. The current role of MEG for presurgical evaluation
      with regard to noninvasive localization in MRI normal patients, guiding of
      invasive electrode implantation and correlation to postoperative outcome after
      epilepsy surgery is stressed. Challenges and future opportunities for MEG in
      clinical epileptology are discussed.

PMID- 27889334
TI  - Leukocytes in expressed breast milk of asthmatic mothers.
AB  - OBJECTIVE: Infants are born immunologically immature. However, breastfeeding
      mothers retain an immunological link to their infants. While it is generally
      accepted that infants are at an immunological advantage when compared with
      formula-fed infants, the benefit of long-term exclusive breastfeeding by atopic
      mothers remains controversial. Inconsistency in the conferral of benefit may be
      due to differences in the immunological constituents passed to the recipient
      infant. The aim of this investigation was to examine the profile of human milk
      cells and cytokines from asthmatic compared to non-asthmatic mothers. METHODS:
      Twenty-five exclusively breastfeeding mothers with a clinical diagnosis of asthma
      were postpartum age matched in a double-control 2:1 design with 50 non-asthmatic
      controls. Each mother provided a single milk sample which was assayed for cell
      differential by flow cytometry, for ex vivo cytokine production in culture and
      for aqueous phase cytokines. RESULTS: Milks from asthmatic mothers differed from
      non-asthmatics in that they contained a higher proportion of polymorphonuclear
      (PMN) cells and lower proportion of lymphocytes, predominantly CD3+/CD4+ T helper
      cells, reflected by a decrease in the chemokine CCL5 in the milk aqueous phase.
      More PMN and lymphocytes from asthmatic mothers expressed the adhesion molecule
      CD11b and lymphocytes the IgE receptor CD23, than those from non-asthmatic
      mothers. CONCLUSIONS: Changes to human milk leucocyte prevalence, activation
      state and cytokines due to maternal asthma may result in changes to immunological
      priming in the infant. Consequently, the protective effect of long-term
      breastfeeding may be altered in these mother-infant pairs.

PMID- 27889335
TI  - Knowledge, perspectives and attitudes about allergen-specific immunotherapy for
      respiratory allergic disease among paediatricians in Turkey.
AB  - BACKGROUND: Allergen-specific immunotherapy (ASI) is the only effective treatment
      for allergic respiratory diseases which has the potential to change the natural
      course of the disease. In this present study we aimed to evaluate the
      paediatricians' knowledge, perspectives and attitudes about ASI for allergic
      respiratory diseases. MATERIALS AND METHODS: The study was conducted between
      September 2014 - January 2015. A survey of 25 questions assessing paediatricians'
      knowledge, perceptions and attitudes about ASI was developed by an expert panel
      and applied by physicians in hospitals in Izmir, Turkey, where the paediatricians
      work. Data were recorded in SPSS for Windows v.16. Descriptive statistics, chi
      square analysis was used. P<0.05 was considered as significant. RESULTS: Fully
      completed surveys from 180 paediatricians were analysed. The respondent
      paediatricians had an age of 37+/-8.2 years, and 56 of them were male. The
      majority of the respondents (n: 146) were working fewer than five years as a
      paediatric specialist. 93.9% of the paediatricians believed that ASI was
      effective for the treatment of allergic respiratory diseases. There was
      satisfactory knowledge of the characteristics, aims, effects and limits of ASI.
      CONCLUSION: ASI is generally well-known and accepted among paediatricians. A
      better synergy between paediatricians and paediatric allergy specialists can
      provide more use of this treatment method for allergic respiratory diseases in
      childhood.

PMID- 27889336
TI  - Characterization of natural polymers from jackfruit pulp, calendula flowers and
      tara seeds as mucoadhesive and controlled release components in buccal tablets.
AB  - Identification and physiochemical parameters such as solubility, loss on drying,
      viscosity, pH, swelling index, starch and gum constituents were determined in
      natural polymers and showed satisfactory results. Spectral studies established
      the compatibility of natural polymers. The drug release kinetics in preliminary
      trial batches showed that tablets containing natural mucilages and gum showed a
      prolonged drug release comparable to Carbopol 974P and Methocel K4M. Also, all
      tablets showed a satisfactory drug permeability flux. Acute toxicity studies
      confirmed the safety of natural polymers. Using response surface method supported
      by 23 factorial design, the optimized buccoadhesive tablets (C1) with drug
      release at 8h (R8h, %) of 53.48+/-0.048% showed controlled release over >=8h and
      followed the Korsmeyer-Peppas model with anomalous (non-Fickian) diffusion
      mechanism. Mucoadhesive strength was found to be 42.71+/-0.49g. Comparative
      dissolution study between prepared and marketed formulation showed that there was
      no significant difference in drug release profile having similarity factor 82.97.
      In vivo study for optimized formulation of the buccoadhesive tablets showed the
      better absolute bioavailability (71.26%) against the oral solution (51.22%).
      Histological study confirmed non-irritant nature and stability study indicated
      stability of the formulation.

PMID- 27889337
TI  - Characterization and analysis of binding of Thioflavin T with partially folded
      and native states of alpha-lactalbumin protein by calorimetric and spectroscopic
      techniques.
AB  - We have analysed binding of Thioflavin T (ThT) with molten globule (MG) and
      native (N) states of alpha-lactalbumin (alpha-LA) by using calorimetry and
      spectroscopy. ThT has been widely used for detection of amyloid fibrils from
      enhancement of its fluorescence emission intensity. Instead of the spectral
      changes of ThT, we, rather, monitored the changes occurring in the spectral
      properties of the MG and N states upon interaction with ThT, from fluorescence,
      absorbance and circular dichroism (CD) spectroscopy. Our novel and most important
      observation is non-fluorescent mode of binding of ThT to the MG state of alpha-LA
      suggesting that the mechanism of binding is distinctly different from that of
      association with the protein fibrils. CD and DLS (Dynamic Light Scattering)
      results show the absence of any major structural and size changes in the protein
      upon ThT binding. The thermodynamic parameters of binding of ThT with the MG and
      N states of alpha-LA obtained from Isothermal Titration Calorimetry (ITC)
      experiments show the formation of stable complex between ThT and alpha-LA (both
      MG and N states) and also provide insights on the probable mode of interaction of
      ThT with the MG and N states of alpha-LA.

PMID- 27889338
TI  - Self-assembling of poly(aspartic acid) with bovine serum albumin in aqueous
      solutions.
AB  - Macromolecular co-assemblies built up in aqueous solutions, by using a linear
      polypeptide, poly(aspartic acid) (PAS), and a globular protein, bovine serum
      albumin (BSA), have been studied. The main interest was to identify the optimum
      conditions for an interpenetrated complex formation in order to design materials
      suitable for biomedical applications, such as drug delivery systems. BSA surface
      possesses several amino- and carboxylic groups available for covalent
      modification, and/or bioactive substances attachment. In the present study,
      mixtures between PAS and BSA were investigated at 37 degrees C in dilute aqueous
      solution by viscometry, dynamic light scattering and zeta potential
      determination, as well as in solid state by AFM microscopy and dielectric
      spectroscopy. The experimental data have shown that the interpolymer complex
      formation occurs for a PAS/BSA molar ratio around 0.541.

PMID- 27889339
TI  - Preparation and copper ions adsorption properties of thiosemicarbazide chitosan
      from squid pens.
AB  - Chitosan was prepared by alkaline N-deacetylation of beta-chitin from squid pens.
      Thiosemicarbazide group was introduced to chitosan via formaldehyde-derived
      linkages, and thiosemicarbazide chitosan (TSFCS) with different degrees of
      substitution (DS) was synthesized. The DS values of TSFCS calculated by elemental
      analysis were 0.19, 0.36 and 0.63. The structure of the TSFCS was confirmed by
      elemental analysis, FTIR, XRD, TGA and SEM. The adsorption capacity of Cu(II)
      ions by TSFCS showed good correlation with the DS and pH (pH range 2.2-5.8). The
      maximum Cu(II) ions adsorption capacity of all three TSFCS samples reached
      134.0mgg-1 at pH 3.6, but chitosan showed no adsorption at this pH. The
      adsorption equilibrium process of Cu(II) ions onto TSFCS was better described by
      the Langmuir model than the Freundlich isotherm model. Cu(II) ions adsorbed by
      TSFCS could be released using 0.01M Na2EDTA and the adsorption capacity could
      retain above 80% after five adsorption-desorption cycles. TSFCS exhibited good
      potential for heavy metal removal because of its high adsorption capacity at the
      low pH.

PMID- 27889340
TI  - Purification and characterization of an antibacterial and anti-inflammatory
      polypeptide from Arca subcrenata.
AB  - A polypeptide coded as PGC was isolated from Arca subcrenata muscle using ion
      exchange, Sephadex G-50 gel chromatography and RP-HPLC. PGC was identified to be
      a homogeneous compound by Native-PAGE and the purity was more than 98.9% measured
      by HPLC. The isoelectric point of PGC was determined to be 9.76 by IEF-PAGE. The
      molecular weight was determined to be 15,973.0Da by ESI-MS/MS. The conformational
      structure of PGC was characterized by UV-vis, FT-IR and CD spectroscopy. N
      terminal amino acid sequence of PGC was shown as
      PSVYDAAAQLTADVKKDLRDSWKVIGGDKKGNGVA by Edman degradation. The results
      demonstrated that there is a high degree of homology between PGC and the subunit
      from hemoglobin, and proposed that PGC is the depolymerized polypeptide of
      Hemoglobin I (HbI) from A. subcrenata. The evaluation of biological activities
      showed that the diameters of the inhibitory ring of PGC on Escherichia coli and
      Staphylococcus aureus were 14.5+/-0.44mm and 16.5+/-1.15mm, respectively. The
      IC50 of inhibition rate for PGC on NO production was 9.60+/-0.71MUg/mL.
      Therefore, PGC might be developed as one of potential antibacterial and anti
      inflammatory agents.

PMID- 27889341
TI  - Facile synthesis of glucoamylase embedded metal-organic frameworks (glucoamylase
      MOF) with enhanced stability.
AB  - The self-assembled glucoamylase metal-organic framework (glucoamylase-MOF) was
      synthesized by facile one-step method within 20min by simply mixing aqueous
      solution of 2-methylimidazole (160mM), glucoamylase (5mg/mL) and zinc acetate
      (40mM) at room temperature (28+/-2 degrees C). The prepared glucoamylase-MOF was
      characterized by using FT-IR, confocal scanning laser microscopy, XRD and SEM.
      The robustness and thermal stability of glucoamylase embedded MOF was evaluated
      in terms of half-life (in the range of 60-80 degrees C) which showed 6 folds
      increment as against free form. Further, in Michaelis-Menten kinetics studies,
      glucoamylase entrapped MOF exhibited higher Km value and lower Vmax value as
      compared to native enzyme. Moreover, the immobilized glucoamylase exhibited up to
      57% of residual activity after six consecutive cycles of reuse, whereas it
      retained 91% of residual activity till 25days of storage. Finally, the
      conformational changes occurred after the encapsulation of glucoamylase in the
      interior of MOF, which was analyzed by using FT-IR data analysis tools.

PMID- 27889342
TI  - A glycosyltransferase gene responsible for pullulan biosynthesis in Aureobasidium
      melanogenum P16.
AB  - In this study, one of the glucosyltransferase genes for pullulan production was
      cloned from Aureobasidum melanogenum P16 and charaterized. It was found that the
      UGT1 gene had 4774bp with four introns (47, 52, 54 and 46bp). The N-terminal part
      of the protein displayed a conserved sequence controlling both sugar donor and
      accepter for substrate specificity whereas its C-terminal part carried a DXD
      motif that coordinated donor sugar binding. After complete removal of the gene
      UGT1, the mutant 1152-3 still produced 27.7+/-3.1g/L of pullulan and 4.6U/g of
      the specific glucosyltransferase activity while its wild type strain P16 yielded
      63.38+/-2.0g/L of pullulan and 5.7U/g of the specific glucosyltransferase
      activity. However, after overexpression of the gene UGT1, the transformant G63
      could produce 78.0+/-3.01g/L of pullulan and 19.0U/g of the specific
      glucosyltransferase activity. It is interesting to note that the molecular weight
      of the produced pullulan by the wild type strain was 4.6*105 while that of the
      produced pullulan by the transformant G63 was 6.2*105. During the 10-Litter
      fermentation, the pullulan titer produced by the transformant G63 reached 80.2+/
      2.0 g/L within 132h.

PMID- 27889343
TI  - An efficient removal of crystal violet dye from waste water by adsorption onto
      TLAC/Chitosan composite: A novel low cost adsorbent.
AB  - A composite of Typha latifolia activated carbon (TLAC) (a novel, low cost
      absorbent) and chitosan (TLAC/Chitosan composite) was prepared. The composite was
      characterised using IR spectra, XRD, FESEM and Pore size studies. Its effectivity
      was tested for the removal of crystal violet dye from aqueous solutions. The
      effect of pH, dose rate and initial dye concentration was evaluated. The
      adsorption isotherm, kinetics and thermodynamic parameters were studied. Langmuir
      and Freundlich isotherm models were found fit effectively for the dye adsorption
      data in the present study. The adsorption followed pseudo-second order kinetics.
      The evaluated thermodynamic parameters show a spontaneous and exothermic
      reaction. Overall, this study indicates TLAC/Chitosan composite as an effective
      adsorbent for the removal of crystal violet dye from aqueous solutions.

PMID- 27889344
TI  - Malabsorption of a Bioresorbable Vascular Scaffold System Leading to Very Late In
      Scaffold Restenosis More Than 3.5 Years After Implantation: Assessment by Optical
      Coherence Tomography.

PMID- 27889345
TI  - Histopathological Differential Diagnosis of Optical Coherence Tomographic Image
      Interpretation After Stenting.
AB  - OBJECTIVES: The aim of this study was to identify histological features that
      correlate with terms commonly used to describe optical coherence tomographic
      (OCT) and optical frequency-domain imaging (OFDI) images of stented vessels, by
      means of a histopathological validation study using stented human coronary
      arteries. BACKGROUND: OCT imaging and OFDI are used to evaluate vascular
      responses to stent implantation. Descriptive terms such as "peristrut low
      attenuation" and "heterogeneous" have been used to describe neointimal
      characteristics that may have clinical relevance. However, only limited
      histopathological correlations are available. METHODS: Using the CVPath stent
      registry, 19 cases were identified in whom implantation duration was >30 days and
      OCT imaging or OFDI and histological findings were available. Consecutive OCT or
      OFDI frames (n = 1,063) of stented coronary arteries were categorized according
      to their predominant imaging features in 1-mm intervals. Coregistration of OCT or
      OFDI frames and histopathological cross sections was performed in 111 frames.
      RESULTS: Seven distinct OCT or OFDI patterns were found: homogenous (45%),
      layered (15%), high intensity with high attenuation (14%), intraluminal
      protruding masses (8%), peristrut low attenuation (7%), heterogeneous (2%), and
      honeycomb (1%). Histopathologically, the homogenous pattern correlated most often
      with smooth muscle cells within collagenous/proteoglycan matrix and less often
      with organized thrombus. The layered pattern correlated with healed neointimal
      rupture or erosion, peristrut neovascularization, or smooth muscle cells within
      collagen/proteoglycan matrix. High intensity with high attenuation correlated
      with superficial macrophage accumulation in the majority of cases, but with other
      histological findings in 30% of cases. The diagnostic accuracy was greater in
      restenotic lesions. The only OCT or OFDI finding that had a single histological
      feature was the honeycomb pattern. CONCLUSIONS: This study suggests a lack of
      correlation between OCT image patterns and distinct histological tissue
      characteristics.

PMID- 27889346
TI  - A Marble in the Heart.

PMID- 27889347
TI  - How Accurate Is Optical Coherence Tomography?

PMID- 27889348
TI  - Percutaneous Stenting of a Left Ventricular Assist Device Outflow Kink.

PMID- 27889349
TI  - Acquired Aseptic Intracardiac Shunts Following Transcatheter Aortic Valve
      Replacement: A Systematic Review.
AB  - OBJECTIVES: The aim of this study was to describe the incidence, mechanisms,
      features, and management of aseptic intracardiac shunts (AICS). BACKGROUND: AICS
      following transcatheter aortic valve replacement (TAVR) are an uncommon and
      barely described complication. METHODS: A systematic review was performed of all
      published cases of AICS following TAVR, and the incidence, predictors, main
      features, management, and related outcomes were analyzed. RESULTS: A total of 31
      post-TAVR AICS were gathered. After excluding transapical fistulas, the 28
      remaining cases corresponded with an incidence of about 0.5%. Mean age and mean
      logistic European System for Cardiac Operative Risk Evaluation score were 80 +/-
      11 years and 19.2 +/- 8.3%, respectively. Prior radiation therapy for cancer was
      present in 14.3%, and 42.8% had severe calcification of the aortic valve. TAVR
      was undertaken using balloon-expandable prostheses in the majority of cases
      (85.7%), via the transapical approach in one-third. Median time from TAVR to
      diagnosis was 21 days (interquartile range: 7 to 30 days), with intraprocedural
      suspicion in 12 cases (42.9%) and a mean Qp/Qs ratio of 1.8 +/- 0.6. The most
      common location for AICS was the interventricular septum (60.7%). Heart failure
      was frequent (46.4%), but 14 patients (50%) remained asymptomatic. Medical
      treatment (71.4%) was associated with poor outcomes (30-day mortality rate 25%),
      especially in symptomatic patients (35% vs. 0%; p = 0.020) and in those with
      higher Qp/Qs ratios (1.9 +/- 0.6 vs. 1.4 +/- 0.1), while cardiac surgery (3.6%),
      and percutaneous closure (25%) led to good outcomes after a median follow-up
      period of 3 months (interquartile range: 1 to 9 months). CONCLUSIONS: Post-TAVR
      AICS are uncommon but have high 30-day mortality if left untreated, especially in
      symptomatic patients. Percutaneous closure was feasible and safe in symptomatic
      patients but remains controversial in asymptomatic subjects.

PMID- 27889350
TI  - Intracardiac Shunts Following Transcatheter Aortic Valve Replacement: Not So Rare
      as to Be Ignored?

PMID- 27889351
TI  - Impella 5.0 Fracture and Transcatheter Retrieval.

PMID- 27889352
TI  - Oxidized glutathione and uric acid as biomarkers of early cystic fibrosis lung
      disease.
AB  - BACKGROUND: In cystic fibrosis (CF) there is an urgent need for earlier diagnosis
      of pulmonary infections and inflammation using blood- and urine-based biomarkers.
      METHODS: Using mass spectrometry, oxidation products of glutathione and uric acid
      were measured in matched samples of bronchoalveolar lavage (BAL), serum and urine
      from 36 infants and children with CF, and related to markers of neutrophilic
      inflammation and infection in BAL. RESULTS: Oxidation products of glutathione
      (glutathione sulfonamide, GSA) and uric acid (allantoin), were elevated in BAL of
      children with pulmonary infections with Pseudomonas aeruginosa (PsA) compared to
      those without (p<0.05) and correlated with other markers of neutrophilic
      inflammation. Serum GSA was significantly elevated in children with PsA
      infections (p<0.01). Urinary GSA correlated with pulmonary GSA (r=0.42, p<0.05)
      and markers of neutrophilic inflammation. CONCLUSIONS: This proof-of-concept
      study demonstrates that urinary GSA but not allantoin shows promise as a non
      invasive marker of neutrophilic inflammation in early CF lung disease.

PMID- 27889353
TI  - Review on fate and mechanism of removal of pharmaceutical pollutants from
      wastewater using biological approach.
AB  - Due to research advancement and discoveries in the field of medical science,
      maintains and provides better human health and safer life, which lead to high
      demand for production of pharmaceutical compounds with a concomitant increase in
      population. These pharmaceutical (biologically active) compounds were not fully
      metabolized by the body and excreted out in wastewater. This micro-pollutant
      remains unchanged during wastewater treatment plant operation and enters into the
      receiving environment via the discharge of treated water. Persistence of
      pharmaceutical compounds in both surface and ground waters becomes a major
      concern due to their potential eco-toxicity. Pharmaceuticals (emerging micro
      pollutants) deteriorate the water quality and impart a toxic effect on living
      organisms. Therefore, from last two decades, plenty of studies were conducted on
      the occurrence, impact, and removal of pharmaceutical residues from the
      environment. This review provides an overview on the fate and removal of
      pharmaceutical compounds via biological treatment process.

PMID- 27889354
TI  - Influence of ozonolysis time during sugarcane pretreatment: Effects on the fiber
      and enzymatic saccharification.
AB  - Modifications in sugarcane bagasse (SCB) from ozonolysis (O) NaOH (B) and
      ultrasound (U) (OBU) treatment for cellulosic ethanol production by enzymatic
      hydrolysis, were evaluated when increasing the exposure time of SCB to ozone. The
      lignin, cellulose, and hemicellulose after treatment were quantified: lignin
      removal and a consequent increase in cellulose content were shown using an
      infrared spectroscopic technique (ATR-FTIR) and chemical characterization. X-ray
      diffraction analysis (XRD) proved that OBU treatment does not affect the
      crystalline cellulose portion and electron microscopy techniques established that
      the fiber region most affected by the OBU treatment was the secondary cell wall,
      where the greatest lignin content is located. For OBU-60 treatment the lignin
      content was reduced and consequently there was a significant increase in
      cellulose content. After enzymatic hydrolysis, this pretreated SCB released
      418mgglucose/g, corresponding to six times more than untreated SCB and a yield of
      93% of the cellulose available.

PMID- 27889355
TI  - Cervical sagittal alignment in adult hyperkyphosis treated by posterior
      instrumentation and in situ bending.
AB  - BACKGROUND: In the normal adult spine, a link between thoracolumbar and cervical
      sagittal alignment exists, suggesting adaptive cervical positional changes
      allowing horizontal gaze. In patients with thoracic hyperkyphosis, cervical
      adaptation to sagittal global alignment might be different from healthy
      individuals. However, this relationship has not clearly been reported in
      hyperkyphotic deformity. PURPOSE: The purpose of this study was to identify
      cervical sagittal alignment types observed on radiographs in young adults with
      thoracic hyperkyphosis. The relationship between cervical and thoracolumbar
      alignment as well as the effect of posterior instrumentation and adaptive
      positional changes of the mobile cervical segment were retrospectively analyzed.
      PATIENTS AND METHODS: Twenty-three patients (32.7 years; 5-year follow-up) were
      included. Full spine radiographic measurements were: T1 slope, T1-T4 kyphosis, T4
      T12 kyphosis, L1-S1 lordosis, pelvic incidence, pelvic tilt, sacral slope, SVA
      C7, SVA C2, lordosis between C0-C2, C2-C7, C2-C4 and C4-C7. A Bayesian model and
      Spearman correlation were used. RESULTS: Two alignment types existed: cervical
      lordosis (group A) and cervical kyphosis (group B). Preoperatively, T4-T12
      kyphosis and L1-S1 lordosis were significantly higher in group A: 76.6 degrees 
      versus 59.4 degrees  and -72.8 degrees  versus -65.8 degrees  (probability of>5
      degrees  difference P (beta>5)>0.95). Pelvic incidence was higher in group A
      (49.8 degrees  versus 44.2 degrees ) and C0-C2 lordosis in group B (-29.4 degrees
      versus -21.6 degrees ). A significant correlation existed between: T4-T12
      kyphosis and C2-C7 lordosis, L1-S1 lordosis and pelvic incidence, C2-C7 lordosis
      and T1 slope, C2-C7 lordosis and T1-T4 kyphosis. Postoperatively, T4-T12 kyphosis
      decreased by 33.1 degrees  P (beta>5)=0.9995), L1-S1 lordosis decreased by 17.7
      degrees  (P (beta>5)=0.961), T1-T4 kyphosis increased by 14.1 degrees  (P
      (beta>5)=0.973). SVA C2 (translation) increased by 13.8mm. C0-C2 lordosis (head
      rotation) remained unchanged. Six patients changed cervical alignment. PJK
      occurred in 15 patients, unrelated to cervical alignment or proximal
      instrumentation level. DISCUSSION: Two cervical alignment types, lordotic or
      kyphotic, were observed thoracic hyperkyphosis patients. This alignment was
      mainly triggered by the amount of thoracic kyphosis and lumbar lordosis, linked
      to pelvic incidence. Moreover, the inclination of the C7-T1 junctional area plays
      a key role in the amount of cervical lordosis. The correction of T4-T12 kyphosis
      induced compensatory modifications at adjacent segments: T1-T4 kyphosis increase
      (PJK) and L1-S1 lordosis decrease. Global spino-pelvic alignment and head
      position did not change in the sagittal plane. The cervical spine tented to keep
      in its preoperative position in most patients. LEVEL OF EVIDENCE: Level IV.

PMID- 27889356
TI  - Role of PTX3 in corneal epithelial innate immunity against Aspergillus fumigatus
      infection.
AB  - Pentraxin3 (PTX3), a member of long pentraxin family, plays a non-redundant role
      in human humoral innate immunity. However, whether PTX3 is expressed by corneal
      epithelial cells and its role during corneal fungi infection has not yet been
      investigated. To identify the presence of PTX3 in cornea, the possible mechanisms
      involved in its expression, and also the effects on corneal anti-fungi innate
      immune response, clinic human corneal tissues and cultured human corneal
      epithelial cells (HCECs) were resorted. PTX3 mRNA and protein were detected in
      corneal samples and cultured HCECs, which was significantly up-regulated after
      exposing to Aspergillus fumigatus (A. fumigatus). Pretreated with specific
      inhibitors, only Syk contributed to the regulation of PTX3 expression in Dectin
      1/Syk signal axis. Furthermore, among the MAPK members (p38 MAPK, ERK1/2 and
      JNK), only ERK1/2 and JNK were responsible for A. fumigatus induced PTX3
      production. Blocking of endogenous PTX3 by siRNA down-regulated the production of
      IL-1beta at both mRNA and protein levels. Meanwhile, blocking of PTX3 also
      inhibited the phosphorylation of ERK1/2 and JNK, but not p38 MAPK. These findings
      demonstrate that PTX3 is expressed in human corneal epithelial cells and Syk,
      ERK1/2, JNK signaling pathways play an important role in the regulation of PTX3
      induction. PTX3 plays a proinflammatory role in corneal epithelial anti-fungi
      immune response by affecting the production of IL-1beta and activation of some
      proinflammatory signaling pathways (ERK1/2 and JNK).

PMID- 27889357
TI  - The impact of overweight/obesity duration and physical activity on telomere
      length: An application of the WATCH paradigm.
AB  - INTRODUCTION: Physical activity may protect against health consequences
      associated with obesity, yet less is known on how the duration of obesity alters
      this association, specifically as it relates to leukocyte telomere length.
      METHODS: The 1999-2002 NHANES was used to place individuals into 6 mutually
      exclusive groups based on physical activity status and weight status/duration.
      RESULTS: All active individuals, except for those overweight/obese for longer
      durations, were associated with longer telomeres in comparison to sedentary
      individuals. CONCLUSIONS: Physical activity may attenuate the decline in telomere
      length associated with obesity, but this protective effect may be negated by
      prolonged periods of overweight/obesity.

PMID- 27889358
TI  - The hypertriglyceridemic waist and waist-to-height ratio phenotypes and chronic
      kidney disease: Cross-sectional and prospective investigations.
AB  - AIMS: We investigated the association between two hypertriglyceridemic waist (HW)
      and waist-to height ratio (HWHtR) phenotypes and chronic kidney disease (CKD)
      using cross sectional and prospective analysis. METHODS: Data of 12,012
      individuals (44% men) of the Tehran Lipid and Glucose Study (TLGS) at two phases
      [(1999-2001) and (2002-2005)], were used for cross-sectional analysis. This
      population was followed until 2014 with median follow-up 12.4 years (95%
      confidence interval (CI): 11.8; 12.4). The data of 8225 individuals (45% men)
      were used for prospective analysis. The outcome was the development of CKD
      defined as estimated glomerular filtration rate (eGFR) <60mL/min/1.73m2. The HW
      phenotype was defined as waist circumference (WC) >90cm in men and >85cm in
      women, along with TGs >2.0mmol/L. The HWHtR phenotype was defined as waist-to
      height ratio (WHtR) >0.5 and TGs >2mmol/L. Multivariable logistic and Cox
      regression were used to statistical analysis. RESULTS: Cross sectional analysis
      showed that in women, both HW and HWHtR phenotypes were associated with CKD after
      controlling for confounders [(OR: 1.37, CI: 1.01-1.86, p<0.05) and (OR: 1.58, CI:
      1.03-2.41, p<0.05)], respectively. Among men, HW and HWHtR were associated with
      prevalent CKD in unadjusted and age adjusted models; these associations were not
      significant after further adjustment for confounders. In prospective analysis,
      neither HW nor HWHtR phenotypes were significant predictor for CKD progression.
      CONCLUSION: HW and HWHtR phenotypes were associated with prevalent CKD in cross
      sectional setting. In prospective analysis HW and HWHtR did not show significant
      effect in prediction of CKD.

PMID- 27889359
TI  - Elevated Liver Enzymes: Emergency Department-Focused Management.
AB  - BACKGROUND: Liver function test (LFT) abnormalities are a common problem faced by
      emergency physicians. This has become more common with the introduction of
      laboratory panels and automated routine laboratory testing. Fortunately, not all
      patients with irregularities in liver enzymes possess underlying pathology. This
      emergency medicine focused review provides a discussion of the various
      biochemical tests, their underlying biological basis, and an algorithmic approach
      to the interpretation of abnormalities. OBJECTIVE: Our aim was to provide
      emergency physicians with an overview of the evaluation and management of
      patients with elevated LFTs. DISCUSSION: The liver is a complex organ with
      multiple roles. The key biochemical markers of hepatic function can be organized
      into the groupings of hepatocellular, cholestatic, or functioning liver, based on
      underlying enzymatic roles. Pathologic alterations to these markers can be
      algorithmically assessed by separating disease processes of these groupings,
      followed by assessment of the magnitude of enzymatic elevation. This review
      conducts an in-depth evaluation of the differential diagnosis and emergency
      department-centered clinical response of elevated LFTs based on subcategories of
      mild, moderate, and severe transaminase elevation. CONCLUSIONS: By understanding
      the biochemical basis of each LFT, it is possible to correlate laboratory
      findings to a patient's clinical presentation. An algorithmic approach can be
      taken to help narrow the spectrum of a differential diagnosis. This may assist
      providers in ensuring appropriate management and evaluation of the patient with
      elevated LFTs.

PMID- 27889360
TI  - Validation of the Exhaled Breath Temperature Measure: Reference Values in Healthy
      Subjects.
AB  - BACKGROUND: Exhaled breath temperature (EBT) is a new noninvasive method for the
      study of inflammatory respiratory diseases with a potential to reach clinical
      practice. However, few studies are available regarding the validation of this
      method, and they were mainly derived from small, pediatric populations; thus, the
      range of normal values is not well established. The aim of this study was to
      measure EBT values in an Italian population of 298 subjects (mean age, 45.2 +/-
      15.5 years; 143 male subjects; FEV1, 97.2% +/- 5.8%; FVC, 98.4% +/- 3.9%)
      selected from 867 adult volunteers to define reference values in healthy subjects
      and to analyze the influence of individual and external variables on this
      parameter. METHODS: EBT was measured with an X-halo PRO device to different
      ambient temperature ranging from 0 degrees C to 38 degrees C. RESULTS: We report
      reference values of EBT in healthy white subjects who had never smoked. EBT
      values were strongly influenced by the external temperature and to a lesser
      extent according to sex. CONCLUSIONS: In a large population of healthy subjects
      who never smoked, these data provide reference values for measuring EBT as a
      basis for future studies. Our results are contribute to the promotion of EBT from
      "bench" to "bedside."

PMID- 27889362
TI  - Erratum to "Spatiotemporal dynamics of cortical perfusion in response to thalamic
      deep brain stimulation" [NeuroImage 126 (2016) 131-139].

PMID- 27889363
TI  - New tools for the hydromorphological assessment and monitoring of European
      streams.
AB  - Hydromorphological stream assessment has significantly expanded over the last
      years, but a need has emerged from recent reviews for more comprehensive, process
      based methods that consider the character and dynamics of the river with greater
      accuracy. With this as a focus, a series of hydromorphological tools have been
      developed and/or further extended in Europe within the context of the REFORM
      (REstoring rivers FOR effective catchment Management) project. The aim of this
      paper is to present the set of REFORM hydromorphological assessment methods and,
      based on some examples of their application, to illustrate and discuss their
      synergic use, specific features, limitations and strengths. This assessment and
      monitoring includes three tools: the Morphological Quality Index (MQI), the
      Morphological Quality Index for monitoring (MQIm), and the Geomorphic Units
      survey and classification System (GUS). These tools constitute the assessment
      phase of an overall multi-scale, process-based hydromorphological framework
      developed in REFORM. The MQI is aimed at an assessment, classification and
      monitoring of the current morphological state; the MQIm aims at monitoring the
      tendency of morphological conditions (enhancement or deterioration); the GUS
      provides a characterization, classification and monitoring of geomorphic units. A
      series of examples are used to illustrate the potential range of application,
      including: (i) an assessment of morphological conditions; (ii) an assessment of
      the morphological effects of restoration projects; (iii) an evaluation of the
      geomorphic impacts of interventions for risk mitigation; and (iv) an integrated
      use of MQI and GUS to assess and characterise morphological conditions. Finally,
      some of the main features, strengths and peculiarities of the three
      hydromorphological tools are discussed with the support of examples of their
      application.

PMID- 27889361
TI  - Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis
      Research Registry.
AB  - OBJECTIVES: We sought to describe the characteristics of adult patients with
      bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR).
      METHODS: The BRR is a database of patients with non-cystic-fibrosis
      bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline
      demographic, spirometric, imaging, microbiological, and therapeutic data were
      entered into a central Internet-based database. Patients were subsequently
      analyzed by the presence of NTM. RESULTS: We enrolled 1,826 patients between 2008
      and 2014. Patients were predominantly women (79%), white (89%), and never smokers
      (60%), with a mean age of 64 +/- 14 years. Sixty-three percent of the patients
      had a history of NTM disease or NTM isolated at baseline evaluation for entry
      into the BRR. Patients with NTM were older, predominantly women, and had
      bronchiectasis diagnosed at a later age than those without NTM. Gastroesophageal
      reflux disease (GERD) was more common in those with NTM, whereas asthma, primary
      immunodeficiency, and primary ciliary dyskinesia were more common in those
      without NTM. Fifty-one percent of patients had spirometric evidence of airflow
      obstruction. Patients with NTM were more likely to have diffusely dilated airways
      and tree-in-bud abnormalities. Pseudomonas and Staphylococcus aureus isolates
      were cultured less commonly in patients with NTM. Bronchial hygiene measures were
      used more often in those with NTM, whereas antibiotics used for exacerbations,
      rotating oral antibiotics, steroid use, and inhaled bronchodilators were more
      commonly used in those without NTM. CONCLUSIONS: Adult patients with
      bronchiectasis enrolled in the US BRR are described, with differences noted in
      demographic, radiographic, microbiological, and treatment variables based on
      stratification of the presence of NTM.

PMID- 27889364
TI  - Metapopulation modelling of riparian tree species persistence in river networks
      under climate change.
AB  - Floodplain landscapes are highly fragmented by river regulation resulting in
      habitat degradation and flood regime perturbation, posing risks to population
      persistence. Climate change is expected to pose supplementary risks in this
      context of fragmented landscapes, and especially for river systems adaptation
      management programs are developed. The association of habitat quality and
      quantity with the landscape dynamics and resilience to human-induced disturbances
      is still poorly understood in the context of species survival and colonization
      processes, but essential to prioritize conservation and restoration actions. We
      present a modelling approach that elucidates network connectivity and landscape
      dynamics in spatial and temporal context to identify vital corridors and
      conservation priorities in the Loire river and its tributaries. Alteration of
      flooding and flow regimes is believed to be critical to population dynamics in
      river ecosystems. Still, little is known of critical levels of alteration both
      spatially and temporally. We applied metapopulation modelling approaches for a
      dispersal-limited tree species, white elm; and a recruitment-limited tree
      species, black poplar. In different model steps the connectivity and natural
      dynamics of the river landscape are confronted with physical alterations
      (dams/dykes) to species survival and then future scenarios for climatic changes
      and potential adaptation measures are entered in the model and translated in
      population persistence over the river basin. For the two tree species we
      highlighted crucial network zones in relation to habitat quality and
      connectivity. Where the human impact model already shows currently restricted
      metapopulation development, climate change is projected to aggravate this
      persistence perspective substantially. For both species a significant drawback to
      the basin population is observed, with 1/3 for elm and 1/4 for poplar after 25
      years already. But proposed adaptation measures prove effective to even bring
      metapopulation strength and persistence up to a level above the current level.

PMID- 27889365
TI  - Characterizing and modelling river channel migration rates at a regional scale:
      Case study of south-east France.
AB  - An increased awareness by river managers of the importance of river channel
      migration to sediment dynamics, habitat complexity and other ecosystem functions
      has led to an advance in the science and practice of identifying, protecting or
      restoring specific erodible corridors across which rivers are free to migrate.
      One current challenge is the application of these watershed-specific goals at the
      regional planning scales (e.g., the European Water Framework Directive). This
      study provides a GIS-based spatial analysis of the channel migration rates at the
      regional-scale. As a case study, 99 reaches were sampled in the French part of
      the Rhone Basin and nearby tributaries of the Mediterranean Sea (111,300 km2). We
      explored the spatial correlation between the channel migration rate and a set of
      simple variables (e.g., watershed area, channel slope, stream power, active
      channel width). We found that the spatial variability of the channel migration
      rates was primary explained by the gross stream power (R2 = 0.48) and more
      surprisingly by the active channel width scaled by the watershed area. The
      relationship between the absolute migration rate and the gross stream power is
      generally consistent with the published empirical models for freely meandering
      rivers, whereas it is less significant for the multi-thread reaches. The
      discussion focused on methodological constraints for a regional-scale modelling
      of the migration rates, and the interpretation of the empirical models. We
      hypothesize that the active channel width scaled by the watershed area is a
      surrogate for the sediment supply which may be a more critical factor than the
      bank resistance for explaining the regional-scale variability of the migration
      rates.

PMID- 27889366
TI  - Intranasal Lidocaine in Acute Treatment of Migraine: A Randomized Controlled
      Trial.
AB  - STUDY OBJECTIVE: The study aims to evaluate the efficacy and safety of intranasal
      lidocaine administration for migraine treatment. METHODS: This single-center,
      double-blind, randomized, controlled trial was conducted in a tertiary care
      emergency department. Included patients met the migraine criteria of the
      International Headache Society. Patients were randomized to intranasal lidocaine
      or saline solution; all participants received 10 mg of intravenous
      metoclopramide. Patient pain intensity was assessed with an 11-point numeric
      rating scale score. The primary outcome measure was the change in pain scores at
      15 minutes; secondary outcomes were changes in pain intensity after pain onset
      and need for rescue medication. RESULTS: Patients (n=162) were randomized into 2
      groups with similar baseline migraine characteristics and numeric rating scale
      scores. The median reduction in numeric rating scale score at 15 minutes was 3
      (interquartile range [IQR] 2 to 5) for the lidocaine group and 2 (IQR 1 to 4) for
      the saline solution group (median difference=1.0; 95% confidence interval 0.1 to
      2.1). The reduction in pain score at 30 minutes was 4 (IQR 3 to 7) for the
      lidocaine group and 5 (IQR 2 to 7) for the saline solution group (median
      difference=1.0; 95% confidence interval 0.1 to 2.1). Need for rescue medication
      did not differ between the groups, and local irritation was the most common
      adverse event in the lidocaine group. CONCLUSION: Although intranasal lidocaine
      was found no more efficacious than normal saline solution in our study, future
      studies should focus on patients who present earlier after headache onset.

PMID- 27889367
TI  - Use or Abuse? A Qualitative Study of Emergency Physicians' Views on Use of
      Observation Stays at Three Hospitals in the United States and England.
AB  - STUDY OBJECTIVE: Accumulating evidence has shown increasing use of observation
      stays for patients presenting to emergency departments and requiring diagnostic
      evaluation or time-limited treatment plans, but critics suggest that this
      expansion arises from hospitals' concerns to maximize revenue and shifts costs to
      patients. Perspectives of physicians making decisions to admit, observe, or
      discharge have been absent from the debate. We examine the views of emergency
      physicians in the United States and England on observation stays, and what
      influences their decisions to use observation services. METHODS: We undertook in
      depth, qualitative interviews with a purposive sample of physicians in 3
      hospitals across the 2 countries and analyzed these using an approach based on
      the constant-comparison method. Limitations include the number of sites, whose
      characteristics are not generalizable to all institutions, and the reliance on
      self-reported interview accounts. RESULTS: Physicians used observation status for
      the specific presentations for which it is well evidenced but acknowledged
      administrative and financial considerations in their decisionmaking. They also
      highlighted an important role for observation not described in the literature: as
      a "safe space," relatively immune from the administrative gaze, where diagnostic
      uncertainties, sociomedical problems, and medicolegal challenges could be
      contained. CONCLUSION: Observation status increases the options available to
      admitting physicians in a way that they valued for its potential benefits to
      patient safety and quality of care, but some of these have been neglected in the
      literature to date. Reform to observation status should address these important
      but previously unacknowledged functions.

PMID- 27889368
TI  - Graph Quality in Top Medical Journals.
AB  - STUDY OBJECTIVE: Well-designed graphs can portray complex data and relationships
      in ways that are easier to interpret and understand than text and tables.
      Previous investigations of reports of clinical research showed that graphs are
      underused and, when used, often depict summary statistics instead of the data
      distribution. This descriptive study aims to evaluate the quantity and quality of
      graphs in the current medical literature across a broad range of better journals.
      METHODS: We performed a cross-sectional survey of 10 randomly selected original
      research articles per journal from the 2012 issues of 20 highly cited journals.
      We identified which figures were data graphs and limited analysis to a maximum of
      5 randomly selected data graphs per article. We then described the graph type,
      data density, completeness, visual clarity, special features, and dimensionality
      of each graph in the sample. RESULTS: We analyzed 342 data graphs published in 20
      journals. Our sample had a geometric mean data density index across all graphs of
      1.18 data elements/cm2. More than half (54%) of the data graphs were simple
      univariate displays such as line or bar graphs. When analyzed by journal,
      excellence in one domain (completeness, visual clarity, or special features) was
      not strongly predictive of excellence in the other domains. CONCLUSION: Despite
      that graphs can efficiently and effectively convey complex study findings, we
      found their infrequent use and low data density to be the norm. The majority of
      graphs were univariate ones that failed to display the overall distribution of
      data.

PMID- 27889369
TI  - Alemtuzumab and de novo pulmonary arterial hypertension: A potential association?

PMID- 27889370
TI  - Malaria Parasites Distribute Subversive Messages across Enemy Lines.
AB  - During its life cycle, the malaria parasite must cope with a set of diverse
      environments and institute strategies to alter its host's responses. A recent
      study remarkably demonstrates how these parasites exploit red blood cell
      products, loading them into 'armed' secreted vesicles sent to manipulate their
      host's 'endothelium battlefront', thereby promoting malaria infection.

PMID- 27889371
TI  - Identification and molecular characterization of Escherichia coli blaSHV genes in
      a Chinese teaching hospital.
AB  - Escherichia coli (E. coli) commonly reside in human intestine and most E. coli
      strains are harmless, but some serotypes cause serious food poisoning. This study
      identified and molecularly characterized blaSHV genes from 490 E. coli strains
      with multi-drug resistance in a hospital population. PCR and molecular cloning
      and southern blot were performed to assess functions and localizations of this
      resistant E. coli gene and the pulsed-field gel electrophoresis (PFGE) was
      utilized to demonstrate the clonal relatedness of the positive E. coli strains.
      The data showed that 4 of these 490 E. coli strains (4/499, 0.8%) carried blaSHV
      genes that included EC D2485 (blaSHV-5), EC D2487 (blaSHV-5), EC D2684 (blaSHV
      11) and EC D2616 (blaSHV-195, a novel blaSHV). Analysis of blaSHV open-reading
      frame showed that blaSHV-5 had a high hydrolysis activity to the broad-spectrum
      penicillin (ampicillin or piperacillin), ceftazidime, ceftriaxone, cefotaxime and
      aztreonam. blaSHV-195 and blaSHV-11 had similar resistant characteristics with
      high hydrolysis activities to ampicillin and piperacillin, but low activities to
      cephalosporins. Moreover, the two blaSHV-5 genes were located on a transferable
      plasmid (23kb), whereas the other two blaSHV variants (blaSHV-11 and blaSHV-195)
      seemed to be located in the chromosomal material. Both EC D2485 and EC D2487
      clones isolated in 2010 had the same DNA finger printing profile and they might
      be the siblings of clonal dissemination. The data from the current study suggest
      that the novel blaSHV and clonal dissemination may be developed, although blaSHV
      genes were infrequently identified in this hospital population. The results of
      the work demonstrate the necessity for molecular surveillance in tracking blaSHV
      producing strains in large teaching hospital settings and emphasize the need for
      epidemiological monitoring.

PMID- 27889372
TI  - [Non-invasive ventilation in children: Do we need more evidence?]
AB  - Respiratory failure is the leading cause of hospital admissions in the pediatric
      intensive care unit (PICU) and is associated with significant morbidity and
      mortality. Mechanical ventilation, preferentially delivered by a non-invasive
      route (NIV), is currently the first-line treatment for respiratory failure since
      it is associated with a reduction in the intubation rate. This ventilatory
      support is increasingly used in the PICU, but its wider use contrasts with the
      paucity of studies in this field. This review aims to describe the main
      indications of NIV in acute settings: (i) bronchiolitis; (ii) postextubation
      respiratory failure; (iii) acute respiratory distress syndrome; (iv) pneumonia;
      (v) status asthmaticus; (vi) acute chest syndrome; (vii) left heart failure;
      (viii) exacerbation of chronic respiratory failure; (ix) upper airway obstruction
      and (x) end-of-life care. Most of these data are based on descriptive studies and
      expert opinions, and few are from randomized trials. While the benefit of NIV is
      significant in some indications, such as bronchiolitis, it is more questionable
      in others. Monitoring these patients for the occurrence of NIV failure markers is
      crucial.

PMID- 27889373
TI  - [Infant respiratory distress revealing Jeune syndrome].
AB  - Jeune syndrome (asphyxiating thoracic dystrophy) is a rare autosomal recessive
      osteochondrodysplasia with a variable degree of severity, clinically
      characterized by respiratory distress with a narrow chest and limb shortness. The
      reported incidence is one to five in 500,000 live births. Most patients develop
      severe respiratory failure during the first 2 years of life, leading to death in
      60-80 % of cases. Survivors may suffer from renal, hepatic, or pancreatic
      complications. Expanding thoracic surgery can be used for severe cases. We
      describe the case of an 18-month-old boy who developed mild respiratory distress.
      The patient showed typical radiological features of Jeune syndrome: narrow thorax
      with short ribs and trident appearance of the pelvis. This case underscores the
      value of the right interpretation of the chest radiograph of the infant with a
      respiratory distress syndrome.

PMID- 27889374
TI  - [Consumption of cannabis in adolescents].
AB  - Over the past 10 years, the consumption of cannabis among adolescents has
      dramatically increased. Today, adolescent cannabis use is a major public health
      problem. Two forms of cannabis are commonly smoked: herb (marijuana) and resin.
      These forms have a high concentration of tetrahydrocannabinol, the active
      molecule of cannabis. Recent research has helped understand how the cannabinoid
      system works. This system combines specific receptors and specific molecules: the
      endocannabinoids. The effects of cannabis use are now well documented. Some
      adolescents report subjective positive effects. They use it not only on a
      recreational basis, but also to deal with their emotions. Over the long term,
      cannabis increases the risk of depression and schizophrenia for those adolescents
      who are at risk. Use, misuse, and dependence are frequently associated with heavy
      psychopathologic problems such as vulnerability and depression. Many cannabis
      dependence psychotherapies have shown their efficacy and efficiency. Motivational
      interviews, cognitive behavioral therapy, multidimensional family therapy (MDFT),
      and residential treatment have proved highly effective. MDFT seems very
      effective, especially in cases of heavy use.

PMID- 27889375
TI  - Integrin alphaMbeta2 is differently expressed by subsets of human osteoclast
      precursors and mediates adhesion of classical monocytes to bone.
AB  - Bone-degrading osteoclasts are formed through fusion of their monocytic
      precursors. In the population of human peripheral blood monocytes, three distinct
      subsets have been identified: classical, intermediate and non-classical
      monocytes. We have previously shown that when the monocyte subsets are cultured
      on bone, significantly more osteoclasts are formed from classical monocytes than
      from intermediate or non-classical monocytes. Considering that this difference
      does not exist when monocyte subsets are cultured on plastic, we hypothesized
      that classical monocytes adhere better to the bone surface compared to
      intermediate and non-classical monocytes. To investigate this, the different
      monocyte subsets were isolated from human peripheral blood and cultured on slices
      of human bone in the presence of the cytokine M-CSF. We found that classical
      monocytes adhere better to bone due to a higher expression of the integrin
      alphaMbeta2 and that their ability to attach to bone is significantly decreased
      when the integrin is blocked. This suggests that integrin alphaMbeta2 mediates
      attachment of osteoclast precursors to bone and thereby enables the formation of
      osteoclasts.

PMID- 27889376
TI  - The cytoplasmic domain of MT1-MMP is dispensable for migration augmentation but
      necessary to mediate viability of MCF-7 breast cancer cells.
AB  - Membrane-type-1 Matrix Metalloproteinase (MT1-MMP) is a multifunctional protease
      that regulates ECM degradation, proMMP-2 activation, and varied cellular
      processes including migration and viability. MT1-MMP is believed to be a central
      mediator of tumourigenesis whose role is dictated by its functionally distinct
      protein domains. Both the localization and signal transduction capabilities of
      MT1-MMP are dependent on its cytoplasmic domain, exemplifying diverse regulatory
      functions. To further our understanding of the multifunctional contributions of
      MT1-MMP to cellular processes, we overexpressed cytoplasmic domain altered
      constructs in MCF-7 breast cancer cells and analyzed migration and viability in
      2D culture conditions, morphology in 3D Matrigel culture, and tumorigenic ability
      in vivo. We found that the cytoplasmic domain was not needed for MT1-MMP mediated
      migration promotion, but was necessary to maintain viability during serum
      depravation in 2D culture. Similarly, during 3D Matrigel culture the cytoplasmic
      domain of MT1-MMP was not needed to initiate a protrusive phenotype, but was
      necessary to prevent colony blebbing when cells were serum deprived. We also
      tested in vivo tumorigenic potential to show that cells expressing cytoplasmic
      domain altered constructs demonstrated a reduced ability to vascularize tumours.
      These results suggest that the cytoplasmic domain regulates MT1-MMP function in a
      manner required for cell survival, but is dispensable for cell migration.

PMID- 27889377
TI  - Retinoid acid-induced microRNA-27b-3p impairs C2C12 myoblast proliferation and
      differentiation by suppressing alpha-dystrobrevin.
AB  - We previously reported that excess retinoic acid (RA) resulted in hypoplastic and
      derangement of myofilaments in embryonic tongue by inhibiting myogenic
      proliferation and differentiation through CamKIID pathway. Our further studies
      revealed that the expression of a series of miRNAs was altered by RA
      administration in embryonic tongue as well as in C2C12 cells. Thus, if excess RA
      impairs myogenic proliferation and differentiation through miRNAs is taken into
      account. In present study, miR-27b-3p was found up-regulated in RA-treated C2C12
      cells as in embryonic tongue, and predicted to target the 3'UTR of alpha
      dystrobrevin (DTNA). Luciferase reporter assays confirmed the direct interaction
      between miR-27b-3p and the 3'UTR of DTNA. MiR-27b-3p mimics recapitulated the RA
      repression on DTNA expression, C2C12 proliferation and differentiation, while the
      miR-27b-3p inhibitor circumvented these defects resulting from excess RA. As
      expected, the effects of siDTNA on C2C12 were coincided with those by RA
      treatment or miR-27b-3p mimics. Therefore, these findings indicated that excess
      RA inhibited the myoblast proliferation and differentiation by up-regulating miR
      27b-3p to target DTNA, which implied a new mechanism in myogenic hypoplasia.

PMID- 27889378
TI  - A Rare Cause of Painful Skin Rash in Crohn's Disease.

PMID- 27889379
TI  - Abdominopelvic CT in a Patient With Seizure, Anemia, and Hypocalcemia.

PMID- 27889380
TI  - A Rare Cause of Generalized Edema.

PMID- 27889381
TI  - Do developmental milestones at 4, 8, 12 and 24 months predict IQ at 5-6 years
      old? Results of the EDEN mother-child cohort.
AB  - RATIONALE: The present study aims: (i) to determine how well developmental
      milestones at 4, 8, 12 and 24 months may predict IQ at 5-6 years old, (ii) to
      identify cognitive domains during the first two years that best predict later IQ
      and (iii) to determine whether children with IQ in the normal range at 5-6 years
      old may differ from disabled (IQ < 70) and gifted children (IQ > 130) with regard
      to their early cognitive development. METHOD: The main developmental milestones
      were collected through self-administered questionnaires rated by parents at 4, 8,
      12 and 24 months and through parental questionnaires administered by a trained
      interviewer and questionnaires completed following a medical examination at 12
      months. These questionnaires were derived from the Brunet-Lezine Psychomotor
      Development Scale and they addressed several cognitive domains (gross and fine
      motor skills, language and socialization). RESULTS: (i) Developmental milestones
      predict a substantial part of the later IQ variance from 24 months (R2 ~ 20%).
      (ii) Early language skills more strongly predict later IQ than the other
      cognitive domains. (iii) Several cognitive domains, but particularly language
      skills, predict disabled children at 5-6 years old (from the age of 8 months) and
      gifted children (from the age of 12 months). DISCUSSION: The present study
      provides valuable information for early developmental assessment and could
      contribute to a better understanding of intellectual development.

PMID- 27889382
TI  - Rare and common variants at 16p11.2 are associated with schizophrenia.
AB  - Recent studies suggest that both common and rare variants are involved in the
      genetic risk of schizophrenia. Using a Cochran-Mantel-Haenszel (CMH) adjusted
      meta-analysis in 36,676 schizophrenia patients and 48,331 healthy controls from
      24 independent samples, we identify the microduplications at 16p11.2 locus (29.6
      30.2Mb, hg19) to be strongly associated with the illness (P value<2.2*10-16, CHM
      adjusted OR=10.79). The frequency of this microduplication is significantly
      higher in schizophrenia patients (0.267%) comparing to healthy controls (0.025%).
      Further, using the largest published genome-wide association study (GWAS) data
      (36,989 cases and 113,075 controls), we show that common variants at the 16p11.2
      locus are also significantly associated with schizophrenia (e.g., rs12691307, P
      value=4.55*10-11, OR=1.073). These results confirm the link between 16p11.2
      genomic region and genetic risk of schizophrenia.

PMID- 27889383
TI  - A systematic review examining factors predicting favourable outcome in cognitive
      behavioural interventions for psychosis.
AB  - Psychosis is a debilitating mental health condition affecting approximately 4
      persons per 1000. Cognitive behavioural therapy for psychosis (CBTp) has been
      shown to be an effective treatment for psychosis and is recommended by several
      national guidelines. CBTp does not work equally well with everyone, however, with
      some 50% of clients receiving little benefit. This review sets out to
      systematically assess the literature and methodological quality of a number of
      studies, which examine factors predicting successful outcome in CBTp. The
      databases CINAHL, Cochrane, EBSCO, EMBASE, ISI Web of Science, MEDLINE (Ovid),
      PsycARTICLES, PsycINFO, PubMed, and Scopus were electronically searched. English
      language articles in peer reviewed journals were reviewed. Search terms
      "psychosis", "psychotic disorder", "cognitive behavioural therapy", "cognitive
      therapy", "randomised controlled trial", "predictor", and "treatment outcome" in
      various combinations were used as needed. Only randomised controlled trials
      (RCTs) were included. Results suggest that female gender, older age, and higher
      clinical insight at baseline, each predicted better outcome in CBT interventions
      with psychotic patients, as did a shorter duration of the illness, and higher
      educational attainment. Several other factors, such as higher symptom severity at
      baseline, were suggestive of predictive capacity but further research to clarify
      was indicated. Providers of mental healthcare should consider these findings when
      offering CBTp. The onus is also on healthcare providers to better equip non
      responders to CBTp. Further investigation into a limited number of predictive
      factors, with an agreed set of outcome measures, would allow future researchers
      more direct comparisons between studies.

PMID- 27889384
TI  - Reduced superoxide dismutase-1 (SOD1) in cerebrospinal fluid of patients with
      early psychosis in association with clinical features.
AB  - Oxidative stress is implicated in the underlying pathophysiology of psychosis
      from studies of animal models and of tissues obtained from patients. Superoxide
      dismutase 1 (SOD1) is an antioxidant responsible for reducing free radicals. SOD1
      levels in cerebrospinal fluid (CSF) reportedly correlate with those in brain. We
      hypothesized that patients in early-stages of psychotic disease may have altered
      SOD1 in CSF compared to healthy controls. We previously reported in a pilot study
      that SOD1 levels in CSF of patients with recent onset schizophrenia (SZ) were
      lower compared to healthy controls. Building on that work, in the present study
      we examined SOD1 levels in CSF acquired from two additional cohorts.
      Specifically, we studied SOD1 levels in CSF from a cohort of 15 patients with
      recent-onset psychosis and 18 healthy controls, as well as the second cohort of
      18 antipsychotic-naive patients with SZ and 20 healthy controls. In the first
      cohort, recent onset of illness was defined as within five years of onset of
      psychotic symptoms, and performance on neuropsychological testing as well as
      symptom severity were assessed. We observed 26.5% lower SOD1 in CSF from patients
      across both cohorts compared to controls (P=0.045) that was consistent with our
      previous report (30%). Among the cohort of patients with recent onset of SZ, SOD1
      in CSF was positively correlated with composite performance on neuropsychological
      testing. Our results support further study of the relationship between cognitive
      deficits and oxidative stress in the central nervous system of patients with
      psychosis, including through study of SOD1.

PMID- 27889385
TI  - Recurrent urinary tract infections in children and adolescents with acute
      psychosis.

PMID- 27889386
TI  - Protein disulfide isomerases: Redox connections in and out of the endoplasmic
      reticulum.
AB  - Protein disulfide isomerases are thiol oxidoreductase chaperones from thioredoxin
      superfamily. As redox folding catalysts from the endoplasmic reticulum (ER),
      their roles in ER-related redox homeostasis and signaling are well-studied. PDIA1
      exerts thiol oxidation/reduction and isomerization, plus chaperone effects. Also,
      substantial evidence indicates that PDIs regulate thiol-disulfide switches in
      other cell locations such as cell surface and possibly cytosol. Subcellular PDI
      translocation routes remain unclear and seem Golgi-independent. The list of
      signaling and structural proteins reportedly regulated by PDIs keeps growing, via
      thiol switches involving oxidation, reduction and isomerization, S
      (de)nytrosylation, (de)glutathyonylation and protein oligomerization. PDIA1 is
      required for agonist-triggered Nox NADPH oxidase activation and cell migration in
      vascular cells and macrophages, while PDIA1-dependent cytoskeletal regulation
      appears a converging pathway. Extracellularly, PDIs crucially regulate thiol
      redox signaling of thrombosis/platelet activation, e.g., integrins, and PDIA1
      supports expansive caliber remodeling during injury repair via
      matrix/cytoskeletal organization. Some proteins display regulatory PDI-like
      motifs. PDI effects are orchestrated by expression levels or post-translational
      modifications. PDI is redox-sensitive, although probably not a mass-effect redox
      sensor due to kinetic constraints. Rather, the "all-in-one" organization of its
      peculiar redox/chaperone properties likely provide PDIs with precision and
      versatility in redox signaling, making them promising therapeutic targets.

PMID- 27889387
TI  - Diet-Microbiome Interactions in Health Are Controlled by Intestinal Nitrogen
      Source Constraints.
AB  - Diet influences health and patterns of disease in populations. How different
      diets do this and why outcomes of diets vary between individuals are complex and
      involve interaction with the gut microbiome. A major challenge for predicting
      health outcomes of the host-microbiome dynamic is reconciling the effects of
      different aspects of diet (food composition or intake rate) on the system. Here
      we show that microbial community assembly is fundamentally shaped by a dichotomy
      in bacterial strategies to access nitrogen in the gut environment. Consequently,
      the pattern of dietary protein intake constrains the host-microbiome dynamic in
      ways that are common to a very broad range of diet manipulation strategies. These
      insights offer a mechanism for the impact of high protein intake on metabolic
      health and form the basis for a general theory of the impact of different diet
      strategies on host-microbiome outcomes.

PMID- 27889388
TI  - Cellular Aging Contributes to Failure of Cold-Induced Beige Adipocyte Formation
      in Old Mice and Humans.
AB  - Cold temperatures induce progenitor cells within white adipose tissue to form
      beige adipocytes that burn energy and generate heat; this is a potential anti
      diabesity therapy. However, the potential to form cold-induced beige adipocytes
      declines with age. This creates a clinical roadblock to potential therapeutic use
      in older individuals, who constitute a large percentage of the obesity epidemic.
      Here we show that aging murine and human beige progenitor cells display a
      cellular aging, senescence-like phenotype that accounts for their age-dependent
      failure. Activating the senescence pathway, either genetically or
      pharmacologically, in young beige progenitors induces premature cellular
      senescence and blocks their potential to form cold-induced beige adipocytes.
      Conversely, genetically or pharmacologically reversing cellular aging by
      targeting the p38/MAPK-p16Ink4a pathway in aged mouse or human beige progenitor
      cells rejuvenates cold-induced beiging. This in turn increases glucose
      sensitivity. Collectively, these data indicate that anti-aging or senescence
      modalities could be a strategy to induce beiging, thereby improving metabolic
      health in aging humans.

PMID- 27889390
TI  - Safety assessment of 4-week oral intake of proanthocyanidin-rich grape seed
      extract in healthy subjects.
AB  - A clinical study was conducted to assess the safety and tolerability of oral
      doses of proanthocyanidin-rich grape seed extract (GSE) in healthy Japanese adult
      volunteers. In an open-label, 4-week toxicity test, 29 subjects daily received
      1000, 1500, or 2500 mg GSE orally. Serum Fe levels of two subjects in the 2500 mg
      GSE group decreased to 61 and 60 MUg/100 mL from 205 and 182 MUg/100 mL at
      baseline respectively, at second week of GSE consumption; these values are low
      but within the normal range for the Japanese population. Two weeks after
      completing the 4-week course of GSE ingestion, the serum Fe levels of both
      subjects returned to near baseline levels (210 and 189 MUg/100 mL). No subject
      discontinued the study. Oral intake of GSE up to 2500 mg for 4 weeks was found to
      be generally safe and well tolerated in humans. Research with a larger number of
      subjects is required to confirm these findings.

PMID- 27889389
TI  - Exercise Mimetics: Impact on Health and Performance.
AB  - The global epidemic of obesity and its associated chronic diseases is largely
      attributed to an imbalance between caloric intake and energy expenditure. While
      physical exercise remains the best solution, the development of muscle-targeted
      "exercise mimetics" may soon provide a pharmaceutical alternative to battle an
      increasingly sedentary lifestyle. At the same time, these advances are fueling a
      raging debate on their escalating use as performance-enhancing drugs in high
      profile competitions such as the Olympics.

PMID- 27889391
TI  - Review of fall detection techniques: A data availability perspective.
AB  - A fall is an abnormal activity that occurs rarely; however, missing to identify
      falls can have serious health and safety implications on an individual. Due to
      the rarity of occurrence of falls, there may be insufficient or no training data
      available for them. Therefore, standard supervised machine learning methods may
      not be directly applied to handle this problem. In this paper, we present a
      taxonomy for the study of fall detection from the perspective of availability of
      fall data. The proposed taxonomy is independent of the type of sensors used and
      specific feature extraction/selection methods. The taxonomy identifies different
      categories of classification methods for the study of fall detection based on the
      availability of their data during training the classifiers. Then, we present a
      comprehensive literature review within those categories and identify the approach
      of treating a fall as an abnormal activity to be a plausible research direction.
      We conclude our paper by discussing several open research problems in the field
      and pointers for future research.

PMID- 27889392
TI  - Transcranial magnetic stimulation to dorsolateral prefrontal cortex affects
      conflict-induced behavioural adaptation in a Wisconsin Card Sorting Test
      analogue.
AB  - A substantial body of literature has proposed a role for dorsolateral prefrontal
      cortex (dlPFC) in supporting behavioural adaptation during conflict tasks. The
      vast majority of the evidence in support of this interpretation comes from
      neuroimaging studies. However, in order to unequivocally ascribe such a role to
      dlPFC, it is important to determine whether or not it is essential for this
      mechanism, and this can only be achieved by lesioning the area or interfering
      with its activity. In this study, we investigated the effects of repeated
      Transcranial Magnetic Stimulation (rTMS) to dlPFC on performance on a conflict
      version of a Wisconsin Card Sorting Test analogue (used previously in
      circumscribed lesion studies in monkeys) in neurologically healthy human
      participants. Our results supported the view of dlPFC as a fundamental structure
      for optimal conflict-induced behavioural adaptation, as stimulation cancelled out
      the adaptation effect normally observed on control trials. We show that there is
      some indication of differential modulation of trial types by stimulation and we
      hypothesize that this might suggest a role for dlPFC in conflict-induced
      adaptation that is more specifically concerned with the maintenance of conflict
      history information online across trials.

PMID- 27889393
TI  - Triple-amiRNA VEGFRs inhibition in pancreatic cancer improves the efficacy of
      chemotherapy through EMT regulation.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal
      outcome. Both novel prognostic markers and therapeutic targets are needed to
      improve the overall outcome of patients. Although single or double VEGFRs have
      been studied in PDAC, little is known about the role of triple combination of
      VEGFRs (VEGFR1, 2, and 3) in prognosis and therapy. We determined VEGFRs protein
      expression in 241 pancreatic tissues by tissue microarray immunohistochemistry
      (TMA-IHC), and correlated with patients' clinical characteristics and overall
      survival. Subsequently, we inactivated VEGFRs expression using artificial
      microRNAs (amiRNAs) in vitro. Triple combination of amiRNAs to VEGFRs reduced
      cell proliferation, increased apoptosis, and reduced cell migration and invasion
      in pancreatic cancer cell lines. In the mouse xenograft pancreatic cancer model,
      triple VEGFRs silencing significantly reduced tumor growth, had synergistic
      effect with standard chemotherapy, and was associated with inhibition of
      epithelial mesenchymal transition (EMT). We conclude that triple combination of
      VEGFRs is a prognostic marker for PDAC, and inhibition of VEGFRs expression via
      amiRNA represents a novel targeted therapy in PDAC through regulating EMT.

PMID- 27889394
TI  - Nanotechnology-based drug delivery systems for Alzheimer's disease management:
      Technical, industrial, and clinical challenges.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in
      the rapidly growing elderly population in the developing world. The currently FDA
      approved drugs for the management of symptomatology of AD are marketed mainly as
      conventional oral medications. Due to their gastrointestinal side effects and
      lack of brain targeting, these drugs and dosage regiments hinder patient
      compliance and lead to treatment discontinuation. Nanotechnology-based drug
      delivery systems (NTDDS) administered by different routes can be considered as
      promising tools to improve patient compliance and achieve better therapeutic
      outcomes. Despite extensive research, literature screening revealed that clinical
      activities involving NTDDS application in research for AD are lagging compared to
      NTDDS for other diseases such as cancers. The industrial perspectives,
      processability, and cost/benefit ratio of using NTDDS for AD treatment are
      usually overlooked. Moreover, active and passive immunization against AD are by
      far the mostly studied alternative AD therapies because conventional oral drug
      therapy is not yielding satisfactorily results. NTDDS of approved drugs appear
      promising to transform this research from 'paper to clinic' and raise hope for AD
      sufferers and their caretakers. This review summarizes the recent studies
      conducted on NTDDS for AD treatment, with a primary focus on the industrial
      perspectives and processability. Additionally, it highlights the ongoing clinical
      trials for AD management.

PMID- 27889395
TI  - [Analysis of direct medical costs of type 2 diabetes in Mali].
AB  - BACKGROUND: Type 2 Diabetes (T2D) is rapidly increasing in Africa, but it is
      still rather neglected. Demonstrating the medical costs for treating type 2
      diabetes would be useful for improving awareness and proposing solutions. The
      purpose of this study was to compare the estimated medical costs for basic
      chronic treatment and the actual expenditures of diabetic patients, and to
      identify determinants of these expenditures. METHODS: The estimated medical costs
      were based on price data collected from three public hospitals and their
      pharmacies (one university and two district hospitals), as well as from three
      private clinics and three private pharmacies, in Bamako. A standard treatment
      protocol for diabetes care, with and without complications, was first established
      by a working group prior to pricing of consultations, medication, care devices
      and specialized tests and treatments. Costs were computed using an Excel(r)
      software program. We calculated actual expenditures for medical care and examined
      some determinants using the data from a cross-sectional survey on 500 adult
      diabetic subjects in Mali. Participants were randomly selected from registries of
      known diabetics. RESULTS: The estimated costs for basic medical care of
      uncomplicated diabetes ranged from 108 to 298 ? per year in the public sector,
      and 325 to 756 ? in the private sector. Median annual expenditures of survey
      subjects without complications for chronic care amounted to 178 ? (range: 98-331)
      and were therefore in the estimated range in the public sector. Total median
      expenditures of all survey subjects, including 78% with complications, reached
      241 ? per year (142-386). Additional expenditures for the treatment of
      complications were lower than the estimated costs, except for retinopathy.
      Independent predictors of higher expenditures were insulin treatment, residence
      in Bamako, and the number of complications. The minimum estimated cost of medical
      treatment for uncomplicated diabetes in the public sector represented 29% of GNP
      per capita. Total medical expenditures as reported by survey respondents amounted
      to an average of 24% of their income. CONCLUSION: Treatment of T2D is expensive
      and beyond reach for many patients in Mali, particularly when there are
      complications. Prevention of diabetes is an urgent challenge in Africa, along
      with early screening in order to delay and reduce the occurrence of
      complications.

PMID- 27889396
TI  - Functional recovery of regional myocardial deformation in patients with takotsubo
      cardiomyopathy.
AB  - BACKGROUND: Takotsubo cardiomyopathy (TC) is acute, but completely reversible in
      the absence of significant coronary artery disease. This study aims to assess the
      functional recovery of regional myocardial deformation in patients with TC using
      2-dimensional (2D) speckle tracking echocardiography. METHODS: Thirty-three
      patients diagnosed with TC (mean age 63 years, 26 female) prospectively underwent
      serial 2D echocardiography on day 1 (initial presentation), day 4 [the middle,
      interquartile range (IQR), 2-5 days], and day 21 (recovery, IQR 13-32 days).
      Twenty-one (64%) patients showed classical type of TC with akinesis of mid-left
      ventricular (LV) and apical segments and 12 (36%) of patients presented with mid
      LV variant with apical sparing. Myocardial deformations were serially assessed
      using 2D strain analysis. All echocardiographic values on day 21 were compared
      with the corresponding values from 30 controls of similar age and gender.
      RESULTS: LV ejection fraction (EF) gradually improved at follow-up (32+/-8% on
      day 1 vs. 62+/-4% on day 21, p<0.001). Despite no difference in LVEF between the
      patients with complete recovery (LVEF >60% on day 21) and controls, the patients
      showed significantly lower global longitudinal strain than controls. On regional
      analysis of the mid-LV segments, both longitudinal and circumferential strains of
      patients with TC were similarly diminished on day 1. During recovery,
      longitudinal strain showed more delayed recovery than circumferential strain
      compared to the values of controls. In LV apex of controls, circumferential
      strain normally presented higher value than longitudinal strain. In LV apex of
      patients with classical TC, the reduced circumferential strain on day 1 rapidly
      increased with a wide variation to maintain augmented circumferential shortening.
      CONCLUSIONS: Quantifying LV myocardial deformation in patients with TC is
      informative in the detection of persistent subtle LV dysfunction and improves our
      understanding of regional myocardial mechanics during recovery.

PMID- 27889397
TI  - Comparative effectiveness of dabigatran and rivaroxaban versus warfarin for the
      treatment of non-valvular atrial fibrillation.
AB  - BACKGROUND: Effectiveness data on novel oral anticoagulants (NOACs) versus
      warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) by
      prior warfarin use are limited. METHODS: We used data from the US MarketScan
      databases from 2009 to 2012. NVAF patients initiating dabigatran or rivaroxaban
      were matched with up to 5 warfarin users. Propensity score-adjusted Cox
      regression was used to calculate hazard ratios (HR) and 95% confidence intervals
      (95% CI) for relevant endpoints in NOACs versus warfarin users. Separate analyses
      were conducted to compare anticoagulant-naive users of NOACs and those switching
      from warfarin. RESULTS: Among 32,918 dabigatran, 3301 rivaroxaban, and 109,447
      warfarin users with NVAF, 225 intracranial bleeds, 1035 ischemic strokes, 958
      myocardial infarctions, and 1842 gastrointestinal bleeds were identified.
      Compared to warfarin users, patients initiating NOACs had similar ischemic stroke
      rates and lower intracranial bleeding rates, while the gastrointestinal bleeding
      rate was higher in dabigatran users than warfarin users. Associations of
      dabigatran with ischemic stroke risk differed between anticoagulant-naive
      initiators and patients switching from warfarin; dabigatran was associated with
      lower ischemic stroke rates in naive users (HR 0.65, 95% CI 0.52-0.82) but not in
      switchers (HR 1.20, 95% CI 0.95-1.51), compared to warfarin. Risk of stroke and
      bleeding was not different between rivaroxaban and warfarin users. CONCLUSIONS:
      Real-world effectiveness of NOACs (compared to warfarin) for diverse outcomes was
      comparable to efficacy reported in published clinical trials. However, harms and
      benefits of switching from warfarin to dabigatran need to be evaluated.

PMID- 27889398
TI  - Recognition of Mycobacterial Lipids by Immune Receptors.
AB  - Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB),
      infects one-third of the world's population and causes 1.5 million deaths each
      year. The cell envelopes of mycobacteria comprise a wealth of unique glycolipids,
      including trehalose-6,6'-dimycolate (TDM), lipoarabinomannan (LAM), lipomannan
      (LM), and phosphatidylinositol (PI) mannosides (PIMs). These lipids are important
      modulators of the host immune responses during infection and in some cases have
      been used as adjuvants [e.g., complete Freund's adjuvant (CFA)]. Despite this
      abundant basic knowledge, the identities of the host immune receptors for
      mycobacterial lipids have long been elusive. Here we review and summarize our
      current state of knowledge regarding innate immune receptors for mycobacteria,
      focusing particularly on immunoreceptor tyrosine-based activation motif (ITAM)
      coupled C-type lectin receptors (CLRs), which have been shown to recognize
      mycobacteria-derived glycolipids.

PMID- 27889399
TI  - A Natural Language Processing-based Model to Automate MRI Brain Protocol
      Selection and Prioritization.
AB  - RATIONALE AND OBJECTIVES: Incorrect imaging protocol selection can contribute to
      increased healthcare cost and waste. To help healthcare providers improve the
      quality and safety of medical imaging services, we developed and evaluated three
      natural language processing (NLP) models to determine whether NLP techniques
      could be employed to aid in clinical decision support for protocoling and
      prioritization of magnetic resonance imaging (MRI) brain examinations. MATERIALS
      AND METHODS: To test the feasibility of using an NLP model to support clinical
      decision making for MRI brain examinations, we designed three different medical
      imaging prediction tasks, each with a unique outcome: selecting an examination
      protocol, evaluating the need for contrast administration, and determining
      priority. We created three models for each prediction task, each using a
      different classification algorithm-random forest, support vector machine, or k
      nearest neighbor-to predict outcomes based on the narrative clinical indications
      and demographic data associated with 13,982 MRI brain examinations performed from
      January 1, 2013 to June 30, 2015. Test datasets were used to calculate the
      accuracy, sensitivity and specificity, predictive values, and the area under the
      curve. RESULTS: Our optimal results show an accuracy of 82.9%, 83.0%, and 88.2%
      for the protocol selection, contrast administration, and prioritization tasks,
      respectively, demonstrating that predictive algorithms can be used to aid in
      clinical decision support for examination protocoling. CONCLUSIONS: NLP models
      developed from the narrative clinical information provided by referring
      clinicians and demographic data are feasible methods to predict the protocol and
      priority of MRI brain examinations.

PMID- 27889400
TI  - Facilitators and Barriers to Implementing Church-Based Adolescent Sexual Health
      Programs in Baltimore City.
AB  - PURPOSE: Black churches are an important community resource and a potentially
      powerful actor in adolescent health promotion. However, limited research exists
      describing the factors that may influence the successful implementation of
      evidence-based adolescent sexual health programs in churches. In the present
      study, a multi-informant approach was used to identify facilitators and barriers
      to implementing adolescent sexual health programs in black churches. METHODS:
      Nine Black churches located in Baltimore, MD, were recruited to participate in
      this study. The senior pastor and youth minster from each congregation
      participated in an in-depth interview (N = 18). A total of 45 youth (ages 13-19
      years) and 38 parents participated in 15 focus groups. Qualitative data were
      transcribed verbatim and analyzed using a qualitative content analytic approach.
      RESULTS: Participants agreed that comprehensive adolescent sexual health
      education should be available for youth in black churches. They also believed
      that abstaining from sex should be discussed in all adolescent sexual health
      programs. Three facilitators were discussed: widespread endorsement of church
      based adolescent sexual health education, positive influence of youth ministers
      on youth, and life lessons as teaching tools. Four barriers are described:
      perceived resistance from congregants, discomfort among youth, lack of financial
      resources, and competing messages at home about sexual health. CONCLUSIONS: Our
      findings suggest that churches are a preferred place for adolescent sexual health
      education among some parents and youth. Study findings also reinforce the
      feasibility and desirably of church-based adolescent sexual health programs.

PMID- 27889401
TI  - Clinical and Psychosocial Outcomes of a Structured Transition Program Among Young
      Adults With Type 1 Diabetes.
AB  - PURPOSE: We identified and treated young adults with type 1 diabetes who had been
      lost to follow-up during their transfer from pediatric to adult care, comparing
      their clinical, psychosocial, and health care utilization outcomes to
      participants receiving continuous care (CC) throughout the transition to adult
      care. METHODS: Individuals in their last year of pediatric care (CC group, n =
      51) and individuals lost to follow-up in the transfer to adult care ("lapsed
      care" [LC] group, n = 24) were followed prospectively for 12 months. All
      participants were provided developmentally tailored diabetes education, case
      management, and clinical care through a structured transition program. RESULTS:
      At baseline, LC participants reported lapses in care of 11.6 months. Compared
      with CC participants, they had higher hemoglobin A1C (A1C; p = .005), depressive
      symptoms (p = .05), incidence of severe hypoglycemia (p = .005), and emergency
      department visits (p = .004). At 12-month follow-up, CC and LC participants did
      not differ on the number of diabetes care visits (p = .23), severe hypoglycemia
      (no events), or emergency department visits (p = .22). Both groups' A1C improved
      during the study period (CC: p = .03; LC: p = .02). LC participants' depressive
      symptoms remained elevated (p = .10), and they reported a decline in life
      satisfaction (p = .007). There was greater loss to follow-up in the LC group (p =
      .04). CONCLUSIONS: Our study suggests that, for young adults with a history of
      lapses in care, a structured transition program is effective in lowering A1C,
      reducing severe hypoglycemia and emergency department utilization, and improving
      uptake of routine diabetes care. Loss to follow-up and psychosocial concerns
      remain significant challenges in this population.

PMID- 27889402
TI  - The Inter-relationship of Adolescent Unhappiness and Parental Mental Distress.
AB  - PURPOSE: Substantial evidence supports the hypothesis that parental well-being
      impacts upon child well-being and that this relationship is bidirectional. Here
      we explore how, in a large, nationally representative sample, both parents'
      mental distress relates over time to each other's mental distress and to their
      adolescent child's unhappiness, and vice versa. METHODS: Analyses were conducted
      using data from waves one to five (2009/10-2014/15) of Understanding Society, the
      UK Household Longitudinal Study. Understanding Society collects data on adults'
      mental distress (General Health Questionnaire), and on youths' (age: 10-15 years)
      unhappiness in relation to their school work, appearance, family, friends,
      school, and life as a whole. We use repeated-measures structural equation models
      to investigate the reciprocal relationships between both parents' distress and
      their child's unhappiness, using both longitudinal cross-lagged and nonrecursive
      contemporaneous specifications. The analytic sample is 1,883 triads (adolescent
      child, mother, and father) with data at two or more consecutive time points.
      Analyses are stratified by adolescent gender. RESULTS: Our results show that
      parental mental distress predicts unhappiness of girls but not that of boys.
      Reciprocal associations of maternal and paternal mental distress are evident in
      families with an adolescent daughter. Unhappiness of adolescents does not predict
      their parents' mental distress. Results are similar whether examined
      contemporaneously or over time. CONCLUSIONS: Our findings support the suggestion
      that the family should be considered as a dynamic system, for instance when
      planning clinical interventions. This is particularly pertinent in families with
      an adolescent daughter present.

PMID- 27889403
TI  - Home Food Rules in Relation to Youth Eating Behaviors, Body Mass Index, Waist
      Circumference, and Percent Body Fat.
AB  - PURPOSE: To investigate agreement and associations between parent and youth
      acknowledgment of home food rules, youth eating behaviors, and measures of body
      composition and excess weight. METHODS: Parent-youth dyads (N = 413) completed
      the "rules for eating at home" scale (Active Where Survey) and reported dietary
      intake. Trained research staff obtained anthropometric data. Linear regression
      analyses separately evaluated relationships between youth and parent
      acknowledgment of rules and youth-reported eating behaviors and anthropometric
      outcomes. Food rules were evaluated as a 12-item scale and individually. RESULTS:
      Score on the food rule scale was positively associated with fruit and vegetable
      servings by youth acknowledgment only (beta = .09, p = .006), and not with
      anthropometric outcomes. The rule "no desserts except fruit" was positively
      associated with fruit and vegetable servings by youth (beta = .72, p = .002) and
      parent (beta = .53, p = .03) acknowledgment. The rules "no second helpings at
      meals" and "limited fast food" were positively associated with body mass index z
      score by youth (beta = .38, p = .002; beta = .32, p = .02, respectively) and
      parent (beta = .74, p < .001; beta = .41, p = .006, respectively) acknowledgment,
      with similar results for waist circumference z-score and percent body fat.
      CONCLUSIONS: Inverse associations between specific food rules and healthful
      eating behaviors but positive associations with anthropometric outcomes suggest
      potentially bidirectional relationships between food rule implementation and
      youth weight. Future studies should disentangle how food rules guide youth
      behavior in the context of youth weight status.

PMID- 27889404
TI  - Adolescent Suicidal Ingestion: National Trends Over a Decade.
AB  - PURPOSE: Suicide attempts by adolescents most commonly involve the overdose of
      medications. To date, there has been little information on the over-the-counter
      or prescription medicines that adolescents ingest for self-harm. Identification
      of medications chosen in suicide attempts may help guide anticipatory guidance to
      parents by primary care providers and Poison Centers in prevention programs.
      METHODS: This was a retrospective observational study using the American
      Association of Poison Control Center's National Poison Data System. Data were
      collected on patients aged 13-19 years old at the time of their substance
      ingestion, between the years 2004 and 2013 and that were coded as reason for
      ingestion of "intentional-suspected suicide." RESULTS: During the 10-year study
      period, there were 390,560 poison center calls for intentional-suspected suicide
      in the United States between 2004 and 2013, accounting for 80.3% of all
      "intentional" ingestion calls in the adolescent population. Over the entire age
      range, the most common substance ingested included acetaminophen (10.9%),
      ibuprofen (9%), selective serotonin reuptake inhibitors (7.7%), atypical
      antipsychotic (6%), and antihistamines (5%). The most common medications coded as
      resulting in major clinical effects or death were antidepressants and atypical
      antipsychotics. CONCLUSIONS: Adolescent ingestion choices for suicide attempts
      have remained relatively consistent over the past 10 years. However, there was a
      recent decrease in selective serotonin reuptake inhibitor ingestions. The most
      common medications used in an overdose attempt were ibuprofen and acetaminophen.
      Further preventative efforts are needed in this at-risk population from multiple
      providers at various levels.

PMID- 27889405
TI  - Primary total knee arthroplasty for elderly complex tibial plateau fractures.
AB  - OBJECTIVE: The aim of this study is to evaluate the clinical and radiologic
      results of primary Total Knee Arthroplasty (TKA) for elderly complex tibial
      plateau fractures. MATERIALS AND METHODS: Between November 2010 and February
      2012, six cases of elderly complex tibial plateau fractures were treated with
      primary TKA using the standard medial parapatellar approach. All six patients
      were available at follow up with mean duration of 32.3 months (range 25-41
      months). There were 3 women and 3 men with an average age of 69.5 years (58-78
      years) at the time of the arthroplasty. RESULTS: The mean Hospital for Special
      Surgery (HSS) knee score was 89.8 (range 85-94): 6/6 excellent. The mean knee
      flexion was 119.2 degrees  (105-130 degrees ). No significant postoperative
      complications were noted. None of these patients had significant postoperative
      knee pain required revision surgery, or had radiographic loosening of the
      components at the latest follow-up. CONCLUSIONS: TKA is a suitable solution for
      the treatment of elderly patients with complex tibial plateau fractures. LEVEL OF
      EVIDENCE: Level IV, Therapeutic study.

PMID- 27889406
TI  - Is surgeons' experience important on intra- and inter-observer reliability of
      classifications used for adult femoral neck fracture?
AB  - PURPOSE: To evaluate whether surgeons' experience affect inter- and intra
      observer reliability among mostly used classification systems for femoral neck
      fractures. MATERIAL AND METHODS: A power point presentation was prepared with 107
      slides which were antero-posterior radiographs of each femoral neck fracture.
      Five residents, 5 orthopaedic surgeons and 5 senior orthopaedic surgeons reviewed
      this presentation and classified the fractures according to Garden, Pauwels and
      AO classifications. The order of the slides was changed and reviews were repeated
      after 3 months. Fleiss kappa and intraclass correlation coefficient values were
      calculated to evaluate inter and intra-observer reliability. RESULTS: Garden and
      AO classifications' inter-observer reliabilities were similar and higher than
      Pauwels classification. Among three experience groups, the inter-observer
      reliability for Garden classification was highest in senior surgeon group, the
      interobserver reliability for AO classification was highest in surgeon group, and
      interobserver reliability of Pauwels classification was highest in low
      experienced groups (residents and surgeons). Intra-observer reliability was
      highest for Garden and lowest for Pauwels classifications. Surgical experience
      was found to be not effective for intraobserver reliability. CONCLUSION: Both
      Garden and AO classifications were more reliable than Pauwels classification.
      Surgical experience was not significantly important on these three classification
      systems' evaluation. LEVEL OF EVIDENCE: Level IV, Diagnostic study.

PMID- 27889407
TI  - Whole-Cell Cancer Vaccines Induce Large Antibody Responses to Carbohydrates and
      Glycoproteins.
AB  - Whole-cell cancer vaccines are a promising strategy for treating cancer, but the
      characteristics of a favorable immune response are not fully understood. New
      insights could enable development of better vaccines, discovery of new antigens,
      and identification of biomarkers of efficacy. Using glyco-antigen microarrays, we
      demonstrate that GVAX Pancreas (a granulocyte macrophage colony-stimulating
      factor-modified whole-cell tumor vaccine) induces large immunoglobulin G and
      immunoglobulin M responses to many antigens, including tumor-associated
      carbohydrates, blood group antigens, alpha-Gal, and bovine fetuin. Antibody
      responses to alpha-Gal, a glycan found in fetal bovine serum (FBS) used to
      produce the vaccine, correlated inversely with overall survival and appear to
      compete with productive responses to the vaccine. H1299 lysate vaccine, produced
      with FBS, also induced responses to alpha-Gal and fetuin but not K562-GM, which
      is produced in serum-free medium. Our results provide new potential biomarkers to
      evaluate productive/unproductive immune responses and suggest that
      removal/reduction of FBS could improve the efficacy of whole-cell vaccines.

PMID- 27889408
TI  - An RNA-Based Fluorescent Biosensor for High-Throughput Analysis of the cGAS-cGAMP
      STING Pathway.
AB  - In mammalian cells, the second messenger (2'-5',3'-5') cyclic guanosine
      monophosphate-adenosine monophosphate (2',3'-cGAMP), is produced by the cytosolic
      DNA sensor cGAMP synthase (cGAS), and subsequently bound by the stimulator of
      interferon genes (STING) to trigger interferon response. Thus, the cGAS-cGAMP
      STING pathway plays a critical role in pathogen detection, as well as
      pathophysiological conditions including cancer and autoimmune disorders. However,
      studying and targeting this immune signaling pathway has been challenging due to
      the absence of tools for high-throughput analysis. We have engineered an RNA
      based fluorescent biosensor that responds to 2',3'-cGAMP. The resulting "mix-and
      go" cGAS activity assay shows excellent statistical reliability as a high
      throughput screening (HTS) assay and distinguishes between direct and indirect
      cGAS inhibitors. Furthermore, the biosensor enables quantitation of 2',3'-cGAMP
      in mammalian cell lysates. We envision this biosensor-based assay as a resource
      to study the cGAS-cGAMP-STING pathway in the context of infectious diseases,
      cancer immunotherapy, and autoimmune diseases.

PMID- 27889409
TI  - Bioactive Compound Screen for Pharmacological Enhancers of Apolipoprotein E in
      Primary Human Astrocytes.
AB  - Pharmacological screening in physiologically relevant brain cells is crucial for
      identifying neuroactive compounds that better translate into in vivo biology and
      efficacious therapeutics. Pharmacological enhancement of apolipoprotein E (apoE),
      a cholesterol-transporting apolipoprotein, has been proposed as a promising
      therapeutic approach for Alzheimer's disease. Several nuclear receptor agonists
      were initially shown to increase brain apoE levels together with ATP-binding
      cassette transporter 1 (ABCA1), but their underlying mechanisms remain unclear.
      To gain an insight on brain apoE regulation, we performed an unbiased high
      throughput screening of known drugs and bioactive compounds in cultured human
      primary astrocytes, the major apoE-producing cell type in the brain. We have
      identified several small molecules that increase apoE secretion via previously
      unknown mechanisms, including those not co-inducing ABCA1. These newly identified
      compounds are active preferentially in human astrocytes but not in an astrocytoma
      cell line, furnishing new tools for investigating biological pathways underlying
      brain apoE production.

PMID- 27889410
TI  - Multiple states of environmental regulation in well-mixed model biospheres.
AB  - The Gaia hypothesis postulates that life influences Earth's feedback mechanisms
      to form a self regulating system. This provokes the question: how can global self
      regulation evolve? Most models demonstrating environmental regulation involving
      life have relied on alignment between local selection and global regulation. In
      these models environment-improving individuals or communities spread to
      outcompete environment degrading individuals/communities, leading to global
      regulation, but this depends on local differences in environmental conditions. In
      contrast, well-mixed components of the Earth system, such as the atmosphere, lack
      local environmental differentiation. These previous models do not explain how
      global regulation can emerge in a system with no well defined local environment,
      or where the local environment is overwhelmed by global effects. We present a
      model of self-regulation by 'microbes' in an environment with no spatial
      structure. These microbes affect an abiotic 'temperature' as a byproduct of
      metabolism. We demonstrate that global self-regulation can arise in the absence
      of spatial structure in a diverse ecosystem without localised environmental
      effects. We find that systems can exhibit nutrient limitation and two temperature
      limitation regimes where the temperature is maintained at a near constant value.
      During temperature regulation, the total temperature change caused by the
      microbes is kept near constant by the total population expanding or contracting
      to absorb the impacts of new mutants on the average affect on the temperature per
      microbe. Dramatic shifts between low temperature regulation and high temperature
      regulation can occur when a mutant arises that causes the sign of the temperature
      effect to change. This result implies that self-regulating feedback loops can
      arise without the need for spatial structure, weakening criticisms of the Gaia
      hypothesis that state that with just one Earth, global regulation has no
      mechanism for developing because natural selection requires selection between
      multiple entities.

PMID- 27889411
TI  - Modelling three-dimensional fungal growth in response to environmental stimuli.
AB  - Most fungi grow by developing complex networks that enable the translocation of
      nutrients over large distances. Spatially explicit mathematical models are able
      to capture both the complexity of the fungal network and the biomass evolution,
      as such providing a powerful alternative to classical modelling paradigms.
      Unfortunately, most of these models restrict growth to two dimensions or confine
      it to a lattice, thereby resulting in unrealistic representations of fungal
      networks. In addition, interactions between fungi and their environment are often
      neglected. In response, this work presents a lattice-free three-dimensional
      fungal growth model that accounts for the interactions between the in silico
      fungus and different substrates and media. A sensitivity analysis was carried out
      to identify the key model parameters for future calibration. Finally, a scenario
      analysis covering a variety of growth conditions was conducted to illustrate the
      broad scope of the model and its ability to replicate in situ growth scenarios.

PMID- 27889412
TI  - Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional
      recovery after brain ischemia.
AB  - This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic
      phytochemical present in Cannabis sativa, on the cognitive and emotional
      impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice.
      Using a multi-tiered behavioral testing battery during 21days, we found that
      BCCAO mice exhibited long-lasting functional deficits reflected by increase in
      anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like
      behavior (day 21). Short-term CBD 10mg/kg treatment prevented the cognitive and
      emotional impairments, attenuated hippocampal neurodegeneration and white matter
      (WM) injury, and reduced glial response that were induced by BCCAO. In addition,
      ischemic mice treated with CBD exhibited an increase in the hippocampal brain
      derived neurotrophic factor (BDNF) protein levels. CBD also stimulated
      neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO
      animals. Collectively, the present results demonstrate that short-term CBD
      treatment results in global functional recovery in ischemic mice and impacts
      multiple and distinct targets involved in the pathophysiology of brain ischemic
      injury.

PMID- 27889413
TI  - Molecular diagnosis of bloodstream infections in onco-haematology patients with
      PCR/ESI-MS technology.
AB  - OBJECTIVES: Onco-haematological patients are prone to develop infections, and
      antibiotic prophylaxis may lead to negative blood cultures. Thus, the
      microbiological diagnosis and subsequent administration of a targeted
      antimicrobial therapy is often difficult. The goal of this study was to evaluate
      the usefulness of IRIDICA (PCR/ESI-MS technology) for the molecular diagnosis of
      bloodstream infections in this patient group. METHODS: A total of 463 whole blood
      specimens from different sepsis episodes in 429 patients were analysed using the
      PCR/ESI-MS platform, comparing the results with those of blood culture and other
      clinically relevant information. RESULTS: The sensitivity of PCR/ESI-MS by
      specimen (excluding polymicrobial infections, n = 25) in comparison with blood
      culture was 64.3% overall, 69.0% in oncological patients, and 59.3% in
      haematological patients. When comparing with a clinical infection criterion,
      overall sensitivity rose to 74.7%, being higher in oncological patients (80.0%)
      than in haematological patients (67.7%). Thirty-one microorganisms isolated by
      culture were not detected by IRIDICA, whereas 42 clinically relevant pathogens
      not isolated by culture were detected moleculary. CONCLUSIONS: PCR/ESI-MS offers
      a reliable identification of pathogens directly from whole blood. While
      additional studies are needed to confirm our findings, the system showed a lower
      sensitivity in onco-haematological patients in comparison with previously
      reported results in patients from the Intensive Care Unit.

PMID- 27889414
TI  - Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co
      administration of sodium-glucose cotransporter inhibitors with dipeptidyl
      peptidase-4 inhibitors in rodents.
AB  - We investigated whether structurally different sodium-glucose cotransporter
      (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4)
      inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral
      glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1
      (beta-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2
      thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess
      the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor
      enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed
      glucose excursions in both normal and diabetic rodents. In DPP4-deficient rats,
      GTB enhanced glucose-induced aGLP-1 elevation without affecting the basal level,
      whereas metformin, previously reported to enhance GLP-1 secretion, increased both
      the basal level and glucose-induced elevation. Oral treatment with canagliflozin
      and TA-1887 also enhanced glucose-induced aGLP-1 elevation when co-administered
      with either teneligliptin or sitagliptin. These data suggest that structurally
      different SGLT2 inhibitors enhance plasma aGLP-1 elevation and suppress glucose
      excursions during OGTT when co-administered with DPP4 inhibitors, regardless of
      the difference in chemical structure. Combination treatment with DPP4 inhibitors
      and SGLT2 inhibitors having moderate SGLT1 inhibitory activity may be a promising
      therapeutic option for improving glycemic control in patients with type 2
      diabetes mellitus.

PMID- 27889415
TI  - Controlled extended octenidine release from a bacterial nanocellulose/Poloxamer
      hybrid system.
AB  - Although bacterial nanocellulose (BNC) has been widely investigated in the last
      10years as drug delivery system, up to now no long-term controlled release of
      drugs could be realized. Therefore, the aim of the present work was the
      development of a BNC-based drug delivery system that provides prolonged retention
      time for the antiseptic octenidine up to one week with improved mechanical and
      antimicrobial properties as well as a high biocompatibility. BNC was modified by
      incorporation of differently concentrated Poloxamers 338 and 407 as micelles and
      gels that were extensively investigated regarding size, surface charge, and
      dynamic viscosity. Depending on type and concentration of the Poloxamer, a
      retarded octenidine release up to one week could be accomplished. Additionally,
      superior material properties such as high compression stability and water binding
      could be achieved. The antimicrobial activity of octenidine against
      Staphylococcus aureus and Pseudomonas aeruginosa was not changed by the use of
      Poloxamers. Excellent biocompatibility of the Poloxamer loaded BNC could be
      demonstrated after local administration in a shell-less hen's egg model. In
      conclusion, a long-term delivery system consisting of BNC and Poloxamer could be
      developed for octenidine as a ready-to-use system e.g. for long-term dermal wound
      treatment.

PMID- 27889416
TI  - Reducing spontaneous recovery and reinstatement of operant performance through
      extinction-cues.
AB  - It has been argued that the response recovery effects share a common mechanism. A
      possible way to test it is evaluating whether the techniques that impaired
      renewal would impair the other recovery effects as well. Two experiments with
      rats used a free operant procedure to explore whether an extinction-cue could
      prevent the spontaneous recovery and reinstatement of an extinguished lever
      pressing. Both experiments consisted of four phases: Acquisition, Extinction and
      Test 1 and Test 2. First, all rats were trained to perform one instrumental
      response (R1) for food in context A, and a different instrumental response (R2)
      for food in context B. Then, responses were extinguished within the same context:
      R1 in context A and R2 in context B. Throughout this phase all rats received
      brief presentations of a tone (extinction-cue). In both experiments animals were
      tested twice. The first test was conducted immediately after the last extinction
      session. In this test, rats received the extinction-cue for both responses.
      During the second test, rats experienced the tone only for R1. In Experiment 1
      rats were tested after 5days, while for Experiment 2 test 2 took place after a
      single session of re-exposure to the food. Both experiments showed a recovery
      effect (spontaneous recovery in Experiment 1 and reinstatement in Experiment 2)
      for both responses. However, a cue featured in extinction attenuated recovery of
      R1 in both experiments when presented on the test. The findings suggest that
      spontaneous recovery, reinstatement and renewal might share a common mechanism.
      In addition, the present data shows that using an extinction-cue could help to
      reduces relapsing of voluntary behaviors.

PMID- 27889417
TI  - Dietary Zinc and Incident Calcium Kidney Stones in Adolescence.
AB  - PURPOSE: We determined the association between dietary zinc intake and incident
      calcium kidney stones in adolescents. We also examined the relationship between
      dietary zinc intake and urinary zinc excretion between cases and controls.
      MATERIALS AND METHODS: We conducted a nested case-control study within a large
      pediatric health care system. Three 24-hour dietary recalls and spot urine
      chemistry analyses were obtained for 30 participants 12 to 18 years old with a
      first idiopathic calcium based kidney stone and 30 healthy controls matched for
      age, sex, race and month of enrollment. Conditional logistic regression models
      were used to estimate the association between daily zinc intake and incident
      calcium kidney stones, adjusting for dietary phytate, protein, calcium, sodium
      and oxalate. Multivariable linear regression was used to estimate the association
      between dietary and urine zinc, adjusting for urine creatinine and dietary
      phytate and calcium. RESULTS: Cases had lower daily zinc intake (8.1 mg) than
      controls (10 mg, p = 0.029). Daily zinc intake of boys and girls with calcium
      stones was 2 mg and 1.2 mg less, respectively, than the daily intake recommended
      by the Institute of Medicine. Odds of incident stones were reduced by 13% for
      every 1 mg increase in daily zinc intake (OR 0.87, 95% CI 0.75-0.99). There was
      an estimated 4.5 MUg/dl increase in urine zinc for every 1 mg increase in dietary
      zinc (p = 0.009), with weak evidence of a smaller increase in urine zinc in cases
      than in controls (interaction p = 0.08). CONCLUSIONS: Decreased dietary zinc
      intake was independently associated with incident calcium nephrolithiasis in this
      population of adolescents.

PMID- 27889418
TI  - A Statewide Intervention Improves Appropriate Imaging in Localized Prostate
      Cancer.
AB  - PURPOSE: We implemented a statewide intervention to improve imaging utilization
      for the staging of patients with newly diagnosed prostate cancer. MATERIALS AND
      METHODS: MUSIC (Michigan Urological Surgery Improvement Collaborative) is a
      quality improvement collaborative comprising 42 diverse practices representing
      approximately 85% of the urologists in Michigan. MUSIC has developed imaging
      appropriateness criteria (prostate specific antigen greater than 20 ng/ml,
      Gleason score 7 or higher and clinical stage T3 or higher) which minimize
      unnecessary imaging with bone scan and computerized tomography. After baseline
      rates of radiographic staging were established in 2012 and 2013, we used
      multidimensional interventions to deploy these criteria in 2014. Imaging
      utilization was then remeasured in 2015 to evaluate for changes in practice
      patterns. RESULTS: A total of 10,554 newly diagnosed patients with prostate
      cancer were entered into the MUSIC registry from January 1, 2012 through December
      31, 2013 and January 1, 2015 through December 31, 2015. Of these patients 7,442
      (79%) and 7,312 (78%) met our criteria to avoid bone scan and computerized
      tomography imaging, respectively. The use of bone scan imaging when not indicated
      decreased from 11.0% at baseline to 6.5% after interventions (p <0.0001). The use
      of computerized tomography when not indicated decreased from 14.7% at baseline to
      7.7% after interventions (p <0.0001). Variability among practices decreased
      substantially after the interventions as well. The use of recommended imaging
      remained stable during these periods. CONCLUSIONS: An intervention aimed at
      appropriate use of imaging was associated with decreased use of bone scans and
      computerized tomography among men at low risk for metastases.

PMID- 27889419
TI  - Validation and Reliability of the Wisconsin Stone Quality of Life Questionnaire.
AB  - PURPOSE: WISQOL (Wisconsin Stone Quality of Life questionnaire) is a disease
      specific, health related quality of life measure designed for patients who form
      kidney stones. The purpose of this study was to demonstrate the external and
      convergent validity of WISQOL and assess its psychometric properties. MATERIALS
      AND METHODS: At the WISQOL creation site (development sample) and at 8
      geographically diverse centers in the United States and Canada (consortium
      sample) patients with a history of kidney stones were recruited. Item response
      option variability, correlation patterns and internal consistency were compared
      between samples. Convergent validity was assessed by patients who completed both
      WISQOL and SF-36v2(r) (36-Item Short Form Health Survey, version 2). RESULTS:
      Results were analyzed in 1,609 patients, including 275 in the development sample
      and 1,334 in the consortium sample. Response option variability patterns of all
      items were acceptable. Internal WISQOL consistency was acceptable. Intersample
      score comparisons revealed few differences. For both samples the domain-total
      WISQOL score correlations exceeded 0.86. Item level analyses demonstrated
      suitable variation, allowing for discriminatory scoring. At the time that they
      completed WISQOL, patients with stones and stone related symptoms scored lowest
      for health related quality of life. Patients with stones but no symptoms and
      those with no stones scored higher. The convergent validity substudy confirmed
      the ability of WISQOL to identify stone specific decrements in health related
      quality of life that were not identified on SF-36v2. CONCLUSIONS: WISQOL is
      internally consistent and discriminates among patients with different stone
      statuses and symptoms. WISQOL is externally valid across the North American
      population. It may be used for multicenter health related quality of life studies
      in kidney stone disease.

PMID- 27889420
TI  - Correlation of phenotypic tests with the presence of the blaZ gene for detection
      of beta-lactamase.
AB  - Staphylococcus aureus and Staphylococcus saprophyticus are the most common and
      most important staphylococcal species associated with urinary tract infections.
      The objective of the present study was to compare and to evaluate the accuracy of
      four phenotypic methods for the detection of beta-lactamase production in
      Staphylococcus spp. Seventy-three strains produced a halo with a diameter <=28mm
      (penicillin resistant) and all of them were positive for the blaZ gene. Among the
      28 susceptible strain (halo >=29mm), 23 carried the blaZ gene and five did not.
      The zone edge test was the most sensitive (90.3%), followed by MIC determination
      (85.5%), but the specificity of the former was low (40.0%). The nitrocefin test
      was the least sensitive (28.9%). However, the nitrocefin test together with the
      disk diffusion method showed the highest specificity (100%). The present results
      demonstrated that the zone edge test was the most sensitive phenotypic test for
      detection of beta-lactamase, although it is still not an ideal test to detect
      this type of resistance since its specificity was low. However, the inhibition
      halo diameter of the penicillin disk can be used together with the zone edge test
      since the same disk is employed in the two tests. Combined analysis of the two
      tests shows a sensitivity of 90.3% and specificity of 100%, proving better
      sensitivity, especially for S. saprophyticus. This is a low-cost test of easy
      application and interpretation that can be used in small and medium-sized
      laboratories where susceptibility testing is usually performed by the disk
      diffusion method.

PMID- 27889421
TI  - Production of native arbuscular mycorrhizal fungi inoculum under different
      environmental conditions.
AB  - In order to obtain an arbuscular mycorrhizal fungi (AMF) native inoculum from
      Sierra de Moa and determine the most appropriate conditions for its big scale
      production, four light and temperature combinations were tested in three plant
      species (Calophyllum antillanum, Talipariti elatum and Paspalum notatum). Growth
      and development parameters, as well as the mycorrhizal functioning of the
      seedlings were evaluated. The natural light treatment under high temperatures (L
      H) was the most suitable for the growth and development of the three plant
      species, showing the highest total biomass values, mainly of root, and a positive
      root-shoot ratio balance. This treatment also promoted higher values of root
      mycorrhizal colonization, external mycelium and AMF spore density. A total of 38
      AMF species were identified among the plants and environmental conditions tested.
      Archaeospora sp.1, Glomus sp.5, Glomus brohultii and G. glomerulatum were
      observed in all the treatments. The L-H condition can be recommended for native
      inoculum production, as it promotes a better expression of the AM symbiosis and
      an elevated production of mycorrhizal propagules.

PMID- 27889422
TI  - Symptomatic pancreatic duct stones in the disconnected bile duct: A case series.
AB  - BACKGROUND: Pancreaticobiliary maljunction (PBM) refers to the union of the
      pancreatic and biliary ducts outside of the duodenal wall. Patients are at
      increased risk of bile duct and gallbladder cancer, likely secondary to
      pancreatic juice refluxing into the biliary tree, and it is recommended that they
      undergo biliary diversion. METHODS: This is a case series of all patients in our
      institution with PBM and bilioenteric anastomosis who presented with symptomatic
      pancreatic duct stones in a disconnected bile duct. IRB approval was obtained
      prior to the initiation of the study. RESULTS: We describe eight cases of this
      finding. All patients underwent ERCP, with stones successfully removed from the
      disconnected bile duct in seven patients and from the pancreatic duct in one
      patient. CONCLUSION: This novel finding has not been described in the medical
      literature, and may become more prevalent as more patients with PBM undergo
      bilioenteric anastomosis.

PMID- 27889423
TI  - TRPV4 ION Channel Is Associated with Scleroderma.

PMID- 27889424
TI  - HIV Vaccines: One Step Closer.
AB  - Currently there is no effective vaccine against human immunodeficiency virus
      (HIV). Four recently published studies in Cell and Immunity now show that using
      planned sequential boosting with antigens to guide the humoral response towards
      broadly neutralizing antibodies could provide a solution to achieving vaccination
      against HIV-1.

PMID- 27889425
TI  - 'Yoga for Lifestyle Diseases': Conference held on 2nd International Day of Yoga
      2016 at Kolar, India.

PMID- 27889426
TI  - A selective review of dharana and dhyana in healthy participants.
AB  - Attention is an important part of the process of meditation. Traditional Yoga
      texts describe two stages of meditation which follow each other in sequence.
      These are meditative focusing (dharana in Sanskrit) and effortless meditation
      (dhyana in Sanskrit). This review evaluated eight experimental studies conducted
      on participants in normal health, who practiced dharana and dhyana. The studies
      included evaluation of autonomic and respiratory variables, eLORETA and sLORETA
      assessments of the EEG, evoked potentials, functional magnetic resonance imaging,
      cancellation task performance and emotional intelligence. The studies differed in
      their sample size, design and the method of practicing dharana and dhyana. These
      factors have been detailed. The results revealed differences between dharana and
      dhyana, which would have been missed if the two stages of meditation had not been
      studied separately.

PMID- 27889427
TI  - Piper betel leaves induces wound healing activity via proliferation of
      fibroblasts and reducing 11beta hydroxysteriod dehydrogenase-1 expression in
      diabetic rat.
AB  - BACKGROUND: Increased oxidative stress and stress enzyme 11beta hydroxysteriod
      dehydrogenase-1 (11beta HSD-1) served as the major contributing factors for
      delayed wound healing in diabetes mellitus (DM). Piper betel (PB) leaves are
      reported to possess anti-diabetic, anti-oxidant and anti-microbial properties.
      OBJECTIVE: The objective was to investigate the effectiveness of topical
      application of PB leaves extract on oxidative stress and 11beta hydroxysteriod
      dehydrogenase-1 (11beta HSD-1) expression in diabetic wounds. MATERIALS AND
      METHODS: A total 64 male Sprague-Dawley rats were randomly chosen. The
      experimental rats received a single intramuscular injection of streptozotocin (45
      mg/kg). Four full thickness (6 mm) wounds were created on the dorsum of each rat.
      The animals were equally divided (n = 8) into four groups based on the days of
      treatment (i.e. days 3 and 7): Control (Ctrl), diabetic untreated (DM-Ctrl),
      diabetic treated with 1% silver nitrate cream (DM-SN) and diabetic treated with
      50 mg/kg of P. betel leaves extract (DM-PB). The rats were sacrificed on day 3
      and 7 of post wound creations. RESULTS: Following day 7 wound creation, topical
      application of PB extract showed significant increase in hydroxyproline content,
      superoxide dismutase (SOD) level and decreased malondialdehyde (MDA) level,
      11beta-HSD-1 enzyme expression in the diabetic wounds compared to untreated
      diabetic wounds. The results were supported by the observations based on
      histological and ultrastructural features of the wound tissue applied with PB
      extract. CONCLUSION: PB leaves extract improved the delayed wound healing in
      diabetes mellitus by decreasing the oxidative stress markers and 11beta HSD-1
      expression.

PMID- 27889428
TI  - Spectroscopic and E-tongue evaluation of medicinal plants: A taste of how rasa
      can be studied.
AB  - BACKGROUND: The use of medicinal plants in Ayurveda is based on rasa, generally
      taken to represent taste as a sensory perception. This chemosensory parameter
      plays an important role in Ayurvedic pharmacology. OBJECTIVE: The aim is to
      explore the use of structuro-functional information deduced from analytical
      techniques for the rasa-based classification of medicinal plants in Ayurveda.
      MATERIALS AND METHODS: Methods of differential sensing and spectroscopic
      metabolomics have been used in select medicinal plants from three different taste
      categories (sweet, pungent and multiple taste): Tribulus terrestris, Vitis
      vinifera and Glycyrrhiza glabra from sweet category; Piper longum, Cuminum
      cyminum and Capsicum annum from pungent group; Emblica officinalis with five
      tastes. While Electronic tongue was used for evaluation of the sensorial property
      of taste, the chemical properties were studied with Nuclear Magnetic Resonance
      (NMR), Fourier Transform InfraRed (FTIR) and Laser Induced Breakdown Spectroscopy
      (LIBS). RESULTS: In terms of taste and phytochemical profiles, all samples were
      unique but with similarities within each group. While the sensor response in E
      tongue showed similarities within the sweet and pungent categories, NMR spectra
      in the aromatic region showed close similarities between the plants in the sweet
      category. The sensory, phytochemical and phytoelemental profiles of E.
      officinalis (with five rasa) in particular, were unique. CONCLUSION: A
      combination of sensorial and chemical descriptors is a promising approach for a
      comprehensive evaluation and fingerprinting of the Ayurvedic pharmacological
      parameter rasa.

PMID- 27889429
TI  - Plasmatic presepsin (sCD14-ST) concentrations in acute pyelonephritis in adult
      patients.
AB  - INTRODUCTION: Presepsin (sCD14-ST) is an emerging biomarker for infection. We
      hypothesized that presepsin could specifically increase during acute
      pyelonephritis and correlate with severity. METHODS: We compared presepsin values
      in patients with acute pyelonephritis and controls, and we assessed its capacity
      to predict bacteraemia and admission in patients. RESULTS: In 312 patients with
      acute pyelonephritis (median age 33years), presepsin concentrations were higher
      than in controls (476 vs 200ng/L, p<0.001). ROC curve indicated an AUC at 0.90
      [for presepsin (vs. 0.99 and 0.98 for CRP and PCT, respectively; p<0.05) and an
      optimal threshold at 340ng/L (74% sensitivity, 94% specificity). Presepsin
      concentrations increased in acute pyelonephritis patients with bacteraemia (614
      vs. 461ng/L, p,=0.001) and in those requiring admission (614ng/L vs. 320ng/L,
      p<0.001). Performance of presepsin to predict bacteraemia [AUC=0.63, 95%CI: 0.55
      0.72] was similar to CRP (AUC=0.64, p=0.87) and less accurate than PCT (AUC=0.78,
      p<0.001). AUC for presepsin to detect the need for admission was 0.67, and
      comparable to CRP (p=0.26) and PCT (p=0.18). CONCLUSION: Presepsin is a valuable
      biomarker to detect patients with acute pyelonephritis. However, it presents mild
      performance to predict bacteraemia and the need for admission, and offers no
      advantage as compared to CRP and PCT.

PMID- 27889430
TI  - Classification of teeth in cone-beam CT using deep convolutional neural network.
AB  - Dental records play an important role in forensic identification. To this end,
      postmortem dental findings and teeth conditions are recorded in a dental chart
      and compared with those of antemortem records. However, most dentists are
      inexperienced at recording the dental chart for corpses, and it is a physically
      and mentally laborious task, especially in large scale disasters. Our goal is to
      automate the dental filing process by using dental x-ray images. In this study,
      we investigated the application of a deep convolutional neural network (DCNN) for
      classifying tooth types on dental cone-beam computed tomography (CT) images.
      Regions of interest (ROIs) including single teeth were extracted from CT slices.
      Fifty two CT volumes were randomly divided into 42 training and 10 test cases,
      and the ROIs obtained from the training cases were used for training the DCNN.
      For examining the sampling effect, random sampling was performed 3 times, and
      training and testing were repeated. We used the AlexNet network architecture
      provided in the Caffe framework, which consists of 5 convolution layers, 3
      pooling layers, and 2 full connection layers. For reducing the overtraining
      effect, we augmented the data by image rotation and intensity transformation. The
      test ROIs were classified into 7 tooth types by the trained network. The average
      classification accuracy using the augmented training data by image rotation and
      intensity transformation was 88.8%. Compared with the result without data
      augmentation, data augmentation resulted in an approximately 5% improvement in
      classification accuracy. This indicates that the further improvement can be
      expected by expanding the CT dataset. Unlike the conventional methods, the
      proposed method is advantageous in obtaining high classification accuracy without
      the need for precise tooth segmentation. The proposed tooth classification method
      can be useful in automatic filing of dental charts for forensic identification.

PMID- 27889431
TI  - Multiclass cancer classification using a feature subset-based ensemble from
      microRNA expression profiles.
AB  - Cancer classification has been a crucial topic of research in cancer treatment.
      In the last decade, messenger RNA (mRNA) expression profiles have been widely
      used to classify different types of cancers. With the discovery of a new class of
      small non-coding RNAs; known as microRNAs (miRNAs), various studies have shown
      that the expression patterns of miRNA can also accurately classify human cancers.
      Therefore, there is a great demand for the development of machine learning
      approaches to accurately classify various types of cancers using miRNA expression
      data. In this article, we propose a feature subset-based ensemble method in which
      each model is learned from a different projection of the original feature space
      to classify multiple cancers. In our method, the feature relevance and redundancy
      are considered to generate multiple feature subsets, the base classifiers are
      learned from each independent miRNA subset, and the average posterior probability
      is used to combine the base classifiers. To test the performance of our method,
      we used bead-based and sequence-based miRNA expression datasets and conducted 10
      fold and leave-one-out cross validations. The experimental results show that the
      proposed method yields good results and has higher prediction accuracy than
      popular ensemble methods. The Java program and source code of the proposed method
      and the datasets in the experiments are freely available at
      https://sourceforge.net/projects/mirna-ensemble/.

PMID- 27889432
TI  - Decrease of high voltage Ca2+ currents in the dentate gyrus granule cells by
      entorhinal amyloidopathy is reversed by calcium channel blockade.
AB  - In the Alzheimer's disease (AD), entorhinal-hippocampal circuit is one of the
      earliest affected networks. There are some evidences indicating abnormal neuronal
      excitability and impaired synaptic plasticity in the dentate gyrus (DG) of AD
      animal model. However, the underlying mechanism leading to DG dysfunction
      particularly in the early phase of AD is not known. Since calcium dyshomeostasis
      has a critical role in the etiology of AD, it is possible that this phenomenon
      precedes electrophysiological alteration in the DG. Here, the effect of the
      amyloid pathogenesis in the entorhinal cortex (EC) on high activated Ca2+
      currents in the DG granule cells was investigated. One week after bilaterally
      injection of amyloid beta (Abeta) 1-42 into the EC, Ca2+ currents in the DG
      granule cells were assessed by whole cell patch clamp. Voltage clamp recording
      showed the amplitude of high voltage calcium currents in the DG granule cells was
      decreased following EC amyloidopathy. However, the Ca2+ current decay was slower
      than control. Double-pulse recording revealed that Ca2+-dependent inactivation of
      calcium current (CDI) was more pronounced in the EC-Abeta group compared to the
      control group. However, chronic treatment by calcium channel blocker (CCBs),
      isradipine or nimodipine, reverse the Ca2+ currents toward the control level. On
      the other hand, there was no significant difference in the calbindin level in the
      DG of different groups. In conclusion, our results suggest that Abeta in the EC
      independent of calbindin level triggers a decreased Ca2+ currents along with
      increased CDI in the DG granule cells which may lead to further
      electrophysiological alterations in these cells, and treatment by CCBs could
      preserve normal calcium current and may ultimately normal function against the
      Abeta toxicity.

PMID- 27889433
TI  - The protective effect of curcumin in Olfactory Ensheathing Cells exposed to
      hypoxia.
AB  - Curcumin, a phytochemical component derived from the rhizomes of Curcuma longa,
      has shown a great variety of pharmacological activities, such as anti
      inflammatory, anti-tumor, anti-depression and anti-oxidant activity. Therefore,
      in the last years it has been used as a therapeutic agent since it confers
      protection in different neurodegenerative diseases, cerebral ischemia and
      excitotoxicity. Olfactory Ensheathing Cells (OECs) are glial cells of the
      olfactory system. They are able to secrete several neurotrophic growth factors,
      promote axonal growth and support the remyelination of damaged axons. OEC
      transplantation has emerged as a possible experimental therapy to induce repair
      of spinal cord injury, even if the functional recovery is still limited. Since
      hypoxia is a secondary effect in spinal cord injury, this in vitro study
      investigates the protective effect of curcumin in OECs exposed to hypoxia.
      Primary OECs were obtained from neonatal rat olfactory bulbs and placed both in
      normal and hypoxic conditions. Furthermore, some cells were grown with basic
      Fibroblast Growth Factor (bFGF) and/or curcumin at different concentration and
      times. The results obtained through immunocytochemical procedures and MTT test
      show that curcumin stimulates cell viability in OECs grown in normal and hypoxic
      conditions. Furthermore, the synergistic effect of curcumin and bFGF is the most
      effective exerting protection on OECs. Since spinal cord injury is often
      accompanied by secondary insults, such as ischemia or hypoxia, our results
      suggest that curcumin in combination with bFGF might be considered a possible
      approach for restoration in injuries.

PMID- 27889434
TI  - Effects of contingent and noncontingent nicotine on lever pressing for liquids
      and consumption in water-deprived rats.
AB  - Nicotine has been proposed to be a primary reinforcer and a reinforcement
      enhancer. To date, no studies have examined whether nicotine enhances
      consummatory behaviors or only operant responding (appetitive behaviors).
      Experiments were designed to test whether contingent and noncontingent nicotine
      enhance lever pressing for and consumption of fluids in water-deprived rats.
      Animals were water-deprived throughout all experiments. They were trained to
      press two levers under a variable interval (VI-20, 1-35s). Their lever pressing
      and water consumption were measured after noncontingent subcutaneous (s.c.)
      injection of nicotine (1mg/kg), and in 3 choice conditions (water and quinine
      solution (18ug/ml); water and nicotine (32ug/ml) solution; quinine (18ug/ml) and
      nicotine (32ug/ml) solutions) where nicotine was thus delivered contingently upon
      lever pressing. The effects of nicotine (1mg/kg; s.c.) on the consumption of
      water in a time-limited free access (1h) paradigm were assessed. Nicotine
      significantly increased lever pressing and the number of earned reinforcements on
      both levers in the two choice conditions and when administered s.c. compared to
      all groups that did not receive nicotine. However, under no condition did animals
      consume more fluids than baseline. Under the time-limited free access condition
      nicotine reduced water consumption. Although our findings do not support a
      reinforcing effect for nicotine, they are consistent with the incentive
      amplification hypothesis. Its relevance for human smoking is yet unclear.

PMID- 27889435
TI  - Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain
      injury.
AB  - High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that
      triggers the inflammatory response during sepsis. However, whether HMGB1 is
      involved in the pathogenesis of septic brain damage is unknown. In this study, we
      investigated the role of HMGB1 in regulating brain injury in a rat model of
      sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce
      septic brain injury. Hematoxylin and eosin staining was used to detect
      pathological changes in the cortex. The cellular localization of HMGB1 was
      determined using immunostaining. Cortical levels of HMGB1, its receptor for
      advanced glycation end-products (RAGE), and downstream effecter, nuclear factor
      kappa-B (NF-kappaB) subunit p65, were detected via western blot.HMGB1was
      increased in the cytoplasm via translocation from the nucleus predominantly in
      neurons. Moreover, RAGE and NF-kappaB p65 were upregulated after septic brain
      injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of
      RAGE and NF-kappaB p65via inhibiting HMGB1 expression in the cytoplasm.
      Collectively, our findings suggest that HMGB1 and its signaling transduction have
      critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might
      be a potential new therapeutic target for septic brain injury.

PMID- 27889436
TI  - Wide Variation Found in Care of Opioid-Exposed Newborns.
AB  - OBJECTIVE: Standardized practices for the management of neonatal abstinence
      syndrome (NAS) are associated with shorter lengths of stay, but optimal protocols
      are not established. We sought to identify practice variations for newborns with
      in utero chronic opioid exposure among hospitals in the Better Outcomes Through
      Research for Newborns (BORN) network. METHODS: Nursery site leaders completed a
      survey about hospitals' policies and practices regarding care for infants with
      chronic opioid exposure (>=3 weeks). RESULTS: The 76 (80%) of 95 respondent
      hospitals were in 34 states, varied in size (<500 to >8000 births and <10 to >200
      opioid-exposed infants per year), with most affiliated with academic centers
      (89%). Most (80%) had protocols for newborn drug exposure screening; 90% used
      risk-based approaches. Specimens included urine (85%), meconium (76%), and
      umbilical cords (10%). Of sites (88%) with NAS management protocols, 77%
      addressed medical management, 72% nursing care, 72% pharmacologic treatment, and
      58% supportive care. Morphine was the most common first-line pharmacotherapy
      followed by methadone. Observation periods for opioid-exposed newborns varied;
      57% observed short-acting opioid exposure for 2 to 3 days, while 30% observed for
      >=5 days. For long-acting opioids, 71% observed for 4 to 5 days, 19% for 2 to 3
      days, and 8% for >=7 days. Observation for NAS occurred mostly in level 1
      nurseries (86%); however, most (87%) transferred to NICUs when pharmacologic
      treatment was indicated. CONCLUSIONS: Most BORN hospitals had protocols for the
      care of opioid-exposed infants, but policies varied widely and characterized
      areas of needed research. Identification of variation is the first step toward
      establishing best practice standards to improve care for this rapidly growing
      population.

PMID- 27889437
TI  - Hypofractionation Is an Acceptable Alternative to Conventional Fractionation in
      the Treatment of Postlumpectomy Ductal Carcinoma In Situ With Radiotherapy.
AB  - PURPOSE: The standard dose of postlumpectomy radiotherapy (RT) for ductal
      carcinoma in situ (DCIS) is 50 Gy in 25 fractions using conventional
      fractionation (CF). However, in invasive carcinoma, hypofractionation (HF) with
      40 to 42.6 Gy in 15 to 16 fractions has largely become a standard of care. The
      purpose of this study was to review the management of postlumpectomy DCIS in
      terms of RT dose-fractionation and its impact on local recurrence (LR), in one of
      the largest Canadian academic centers. METHODS AND MATERIALS: Between 2003 and
      2008, a total of 348 women with DCIS were treated with postlumpectomy RT. Patient
      characteristics, histopathology, dose-fractionation, use of endocrine therapy,
      local, regional, contralateral breast recurrences, and cause of death were
      collected. Local recurrence-free survival was determined. Univariate and
      multivariate analyses were performed to identify risk factors for LR. RESULTS:
      The median age of the cohort was 59 years. Two hundred two (58%) patients
      received CF and 146 (42%) HF. Initially, the yearly proportion of HF was 34%, but
      increased up to 68% since 2007. Estrogen receptor was positive in 195 patients,
      and 43% of those received endocrine therapy. With a median follow-up of 64.8
      months, 36 LRs were detected. The 5-year local recurrence-free survival rate was
      94% for the HF group versus 91% for the CF group (P = .80). On multivariate
      analysis, only the use of endocrine therapy showed a trend towards decreasing LR
      (hazard ratio, 0.44; 95% confidence interval, 0.18-1.08; P = .07). CONCLUSIONS:
      The utilization of HF for DCIS postlumpectomy has increased over time and is a
      valid option as it results in similar rates of local control.

PMID- 27889438
TI  - Disparities in Surgical Treatment of Early-Stage Breast Cancer Among Female
      Residents of Texas: The Role of Racial Residential Segregation.
AB  - INTRODUCTION: Early-stage breast cancer can be surgically treated by using
      mastectomy or breast-conserving surgery and adjuvant radiotherapy, also known as
      breast-conserving therapy (BCT). Little is known about the association between
      racial residential segregation, year of diagnosis, and surgical treatment of
      early-stage breast cancer, and whether racial residential segregation influences
      the association between other demographic characteristics and disparities in
      surgical treatment. METHODS: This was a retrospective study using data from the
      Texas Cancer Registry composed of individuals diagnosed with breast cancer
      between 1995 and 2012. The dependent variable was treatment using mastectomy or
      BCT (M/BCT) and the independent variables of interest (IVs) were racial
      residential segregation and year of diagnosis. The covariates were race,
      residence, ethnicity, tumor grade, census tract (CT) poverty level, age at
      diagnosis, stage at diagnosis, and year of diagnosis. Bivariate and multivariable
      multilevel logistic regression models were estimated. The final sample size was
      69,824 individuals nested within 4335 CTs. RESULTS: Adjusting for the IVs and all
      covariates, there were significantly decreased odds of treatment using M/BCT, as
      racial residential segregation increased from 0 to 1 (odds ratio [OR] 0.47; 95%
      confidence interval [CI], 0.41-0.54). There was also an increased likelihood of
      treatment using M/BCT with increasing year of diagnosis (OR 1.14; 95% CI, 1.13
      1.16). A positive interaction effect between racial residential segregation and
      race was observed (OR 0.56; 95% CI, 0.36-0.88). CONCLUSION: Residents of areas
      with high indices of racial residential segregation were less likely to be
      treated with M/BCT. Racial disparities in treatment using M/BCT increased with
      increasing racial residential segregation.

PMID- 27889439
TI  - When a gold standard isn't so golden: Lack of prediction of subjective sleep
      quality from sleep polysomnography.
AB  - BACKGROUND: Reports of subjective sleep quality are frequently collected in
      research and clinical practice. It is unclear, however, how well polysomnographic
      measures of sleep correlate with subjective reports of prior-night sleep quality
      in elderly men and women. Furthermore, the relative importance of various
      polysomnographic, demographic and clinical characteristics in predicting
      subjective sleep quality is not known. We sought to determine the correlates of
      subjective sleep quality in older adults using more recently developed machine
      learning algorithms that are suitable for selecting and ranking important
      variables. METHODS: Community-dwelling older men (n=1024) and women (n=459), a
      subset of those participating in the Osteoporotic Fractures in Men study and the
      Study of Osteoporotic Fractures study, respectively, completed a single night of
      at-home polysomnographic recording of sleep followed by a set of morning
      questions concerning the prior night's sleep quality. Questionnaires concerning
      demographics and psychological characteristics were also collected prior to the
      overnight recording and entered into multivariable models. Two machine learning
      algorithms, lasso penalized regression and random forests, determined variable
      selection and the ordering of variable importance separately for men and women.
      RESULTS: Thirty-eight sleep, demographic and clinical correlates of sleep quality
      were considered. Together, these multivariable models explained only 11-17% of
      the variance in predicting subjective sleep quality. Objective sleep efficiency
      emerged as the strongest correlate of subjective sleep quality across all models,
      and across both sexes. Greater total sleep time and sleep stage transitions were
      also significant objective correlates of subjective sleep quality. The amount of
      slow wave sleep obtained was not determined to be important. CONCLUSIONS:
      Overall, the commonly obtained measures of polysomnographically-defined sleep
      contributed little to subjective ratings of prior-night sleep quality. Though
      they explained relatively little of the variance, sleep efficiency, total sleep
      time and sleep stage transitions were among the most important objective
      correlates.

PMID- 27889441
TI  - Corrections.

PMID- 27889440
TI  - Non-heat shock responsive roles of HSF1 in Candida albicans are essential under
      iron deprivation and drug defense.
AB  - Recently, we have reported that the conditional mutant of the heat shock factor-1
      (HSF1) in Candida albicans displays enhanced susceptibility not only towards a
      plant alkaloid, berberine, but also to diverse antifungal drugs. The present
      study attempts to identify additional phenotypes highlighting the non-heat shock
      responsive roles of HSF1 that could be correlated with the enhanced drug
      susceptibility. We uncover an intricate relationship between cellular iron and
      HSF1 mediated drug susceptibility of C. albicans. Interestingly, at 30 degrees C,
      the conditional deletion of HSF1 while presented no growth defect, exhibited low
      intracellular iron. Notably, exogenous supplementation of iron reversed growth
      defects of HSF1 mutant when grown at 37 degrees C. We provide evidence that the
      HSF1 mutant presents interesting phenotypes at basal conditions and are
      implicated in enhanced drug susceptibilities, dysfunctional mitochondria,
      decreased resistance towards oxidative stress and compromised cell wall
      integrity, all of which could be fully reversed upon iron supplementation. The
      HSF1 mutant also displayed defective filamentation at basal conditions under
      various solid hypha inducing media. Further, chelation of iron of HSF1 mutant
      cells led to severe growth defects and apparently triggers an iron starvation
      signal in the cell thus, demonstrating that HSF1 is essential for C. albicans
      cells to tolerate the iron deprivation stress. Together, apart from the well
      established roles of HSF1 in reciprocation of thermal stress, this study extends
      its role under basal conditions and provides molecular insights into the role of
      HSF1 in iron deprivation and drug defense of C. albicans.

PMID- 27889442
TI  - Current perspectives in the interpretation of gunshot residues in forensic
      science: A review.
AB  - The traces produced when a firearm is discharged can provide important
      information in cases when questions regarding a possible association of the
      firearm with a person of interest (POI), time since discharge or shooting
      distance are raised. With advances in technology, the forensic challenges
      presented by these traces, known as gunshot residues (GSR), are moving from the
      analytical domain to the interpretation of the analytical results. Different
      interpretation frameworks are currently competing. Formal classification of
      particles, using standards such as that produced by ASTM, focusses only on
      evaluation of evidence at the sub-source level. Another approach, based on the
      application of Bayesian reasoning - namely the case-by-case approach - has been
      proposed that allows evaluation of evidence in regards to activity-related
      questions. This alternative approach allows an evaluation of the evidence that is
      more closely aligned to judicial and investigative aims. This paper critically
      presents the state of the art in regards to GSR interpretation in a holistic
      manner.

PMID- 27889443
TI  - The application of silicon sol-gel technology to forensic blood substitute
      development: Mimicking aspects of whole human blood rheology.
AB  - Solution-gelation chemistry has promising applications in forensic synthetic
      blood substitute development. This research offers a silicon-based sol-gel
      approach to creating stable materials that share similar rheological properties
      to that of whole human blood samples. Room temperature, high water content,
      silicon sol-gels were created using the organosilane precursors 3
      glycidoxypropyltrimethoxysilane and tetraethylorthosilicate along with various
      concentrations of filler and pigment. Shear-thinning non-Newtonian properties
      were observed within most formulations of the presented materials. The effects of
      colloidal concentration, temperature, age and filler addition on the viscosity of
      the sol-gels were investigated. SEM-EDS analysis was used to identify the
      behavior of the fillers within the film and support their inclusion for basic
      bloodstain pattern simulation. A final proposed candidate sol-gel was assessed
      using a previously reported passive drip simulation test on a hard, dry surface
      and passed. This works represents encouraging development in providing safe
      material alternatives to using whole human blood for forensic training and
      research.

PMID- 27889444
TI  - The Effectiveness of Emotional Freedom Techniques in the Treatment of
      Posttraumatic Stress Disorder: A Meta-Analysis.
AB  - BACKGROUND: Over the past two decades, growing numbers of clinicians have been
      utilizing emotional freedom techniques (EFT) in the treatment of posttraumatic
      stress disorder (PTSD), anxiety, and depression. Randomized controlled trials
      (RCTs) have shown encouraging outcomes for all three conditions. OBJECTIVE: To
      assess the efficacy of EFT in treating PTSD by conducting a meta-analysis of
      existing RCTs. METHODS: A systematic review of databases was undertaken to
      identify RCTs investigating EFT in the treatment of PTSD. The RCTs were evaluated
      for quality using evidence-based standards published by the American
      Psychological Association Division 12 Task Force on Empirically Validated
      Therapies. Those meeting the criteria were assessed using a meta-analysis that
      synthesized the data to determine effect sizes. While uncontrolled outcome
      studies were excluded, they were examined for clinical implications of treatment
      that can extend knowledge of this condition. RESULTS: Seven randomized controlled
      trials were found to meet the criteria and were included in the meta-analysis. A
      large treatment effect was found, with a weighted Cohen's d = 2.96 (95% CI: 1.96
      3.97, P < .001) for the studies that compared EFT to usual care or a waitlist. No
      treatment effect differences were found in studies comparing EFT to other
      evidence-based therapies such as eye movement desensitization and reprocessing
      (EMDR; 1 study) and cognitive behavior therapy (CBT; 1 study). CONCLUSIONS: The
      analysis of existing studies showed that a series of 4-10 EFT sessions is an
      efficacious treatment for PTSD with a variety of populations. The studies
      examined reported no adverse effects from EFT interventions and showed that it
      can be used both on a self-help basis and as a primary evidence-based treatment
      for PTSD.

PMID- 27889445
TI  - Mindfulness Training for Health Profession Students-The Effect of Mindfulness
      Training on Psychological Well-Being, Learning and Clinical Performance of Health
      Professional Students: A Systematic Review of Randomized and Non-randomized
      Controlled Trials.
AB  - BACKGROUND: High levels of stress have been identified in medical students and
      increasingly in other health profession student population groups. As stress can
      affect psychological well-being and interfere with learning and clinical
      performance, there is a clear argument for universities to include health
      professional student well-being as an outcome in core curriculum. Mindfulness
      training is a potential construct to manage stress and enhance academic success.
      OBJECTIVES: The aims of this systematic review were to assess the effectiveness
      of mindfulness training in medical and other health professional student
      population groups and to compare the effectiveness of the different mindfulness
      based programs. DATA SOURCES: A literature search was completed using The
      Cochrane library, Medline, Cinahl, Embase, Psychinfo, and ERIC (proquest)
      electronic databases from inception to June 2016. Randomized and non-randomized
      controlled trials were included. Of the potential 5355 articles, 19 met the
      inclusion criteria. STUDY SELECTION PARTICIPANTS AND INTERVENTIONS: Studies
      focused on medical (n = 10), nursing (n = 4), social work (n = 1), psychology (n
      = 1), and medical plus other health (n = 3) students. Interventions were based on
      mindfulness. DATA EXTRACTION: The 19 studies included 1815 participants. Meta
      analysis was performed evaluating the effect of mindfulness training on
      mindfulness, anxiety, depression, stress, mood, self-efficacy, and empathy. The
      effect of mindfulness on academic performance was discussed. DATA SYNTHESIS AND
      CONCLUSIONS: Mindfulness-based interventions decrease stress, anxiety, and
      depression and improve mindfulness, mood, self-efficacy, and empathy in health
      profession students. Due to the range of presentation options, mindfulness
      training can be relatively easily adapted and integrated into health professional
      training programs.

PMID- 27889446
TI  - Fear, Courage and Finding the Way Forward.

PMID- 27889447
TI  - Dietary Supplement Use Among Adults Remains Consistent Over 12 Years.

PMID- 27889448
TI  - Inhibition of Ras/Raf/MEK/ERK Pathway Signaling by a Stress-Induced Phospho
      Regulatory Circuit.
AB  - Ras pathway signaling plays a critical role in cell growth control and is often
      upregulated in human cancer. The Raf kinases selectively interact with GTP-bound
      Ras and are important effectors of Ras signaling, functioning as the initiating
      kinases in the ERK cascade. Here, we identify a route for the phospho-inhibition
      of Ras/Raf/MEK/ERK pathway signaling that is mediated by the stress-activated JNK
      cascade. We find that key Ras pathway components, the RasGEF Sos1 and the Rafs,
      are phosphorylated on multiple S/TP sites in response to JNK activation and that
      the hyperphosphorylation of these sites renders the Rafs and Sos1 unresponsive to
      upstream signals. This phospho-regulatory circuit is engaged by cancer
      therapeutics, such as rigosertib and paclitaxel/Taxol, that activate JNK through
      mitotic and oxidative stress as well as by physiological regulators of the JNK
      cascade and may function as a signaling checkpoint to suppress the Ras pathway
      during conditions of cellular stress.

PMID- 27889449
TI  - Phosphorylated CtIP Functions as a Co-factor of the MRE11-RAD50-NBS1 Endonuclease
      in DNA End Resection.
AB  - To repair a DNA double-strand break (DSB) by homologous recombination (HR), the
      5'-terminated strand of the DSB must be resected. The human MRE11-RAD50-NBS1
      (MRN) and CtIP proteins were implicated in the initiation of DNA end resection,
      but the underlying mechanism remained undefined. Here, we show that CtIP is a co
      factor of the MRE11 endonuclease activity within the MRN complex. This function
      is absolutely dependent on CtIP phosphorylation that includes the key cyclin
      dependent kinase target motif at Thr-847. Unlike in yeast, where the Xrs2/NBS1
      subunit is dispensable in vitro, NBS1 is absolutely required in the human system.
      The MRE11 endonuclease in conjunction with RAD50, NBS1, and phosphorylated CtIP
      preferentially cleaves 5'-terminated DNA strands near DSBs. Our results define
      the initial step of HR that is particularly relevant for the processing of DSBs
      bearing protein blocks.

PMID- 27889450
TI  - RPA Mediates Recruitment of MRX to Forks and Double-Strand Breaks to Hold Sister
      Chromatids Together.
AB  - The Mre11-Rad50-Xrs2 (MRX) complex is related to SMC complexes that form rings
      capable of holding two distinct DNA strands together. MRX functions at stalled
      replication forks and double-strand breaks (DSBs). A mutation in the N-terminal
      OB fold of the 70 kDa subunit of yeast replication protein A, rfa1-t11, abrogates
      MRX recruitment to both types of DNA damage. The rfa1 mutation is functionally
      epistatic with loss of any of the MRX subunits for survival of replication fork
      stress or DSB recovery, although it does not compromise end-resection. High
      resolution imaging shows that either the rfa1-t11 or the rad50Delta mutation lets
      stalled replication forks collapse and allows the separation not only of opposing
      ends but of sister chromatids at breaks. Given that cohesin loss does not provoke
      visible sister separation as long as the RPA-MRX contacts are intact, we conclude
      that MRX also serves as a structural linchpin holding sister chromatids together
      at breaks.

PMID- 27889451
TI  - Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple
      Host Tissues.
AB  - Histone-modifying enzymes regulate transcription and are sensitive to
      availability of endogenous small-molecule metabolites, allowing chromatin to
      respond to changes in environment. The gut microbiota produces a myriad of
      metabolites that affect host physiology and susceptibility to disease; however,
      the underlying molecular events remain largely unknown. Here we demonstrate that
      microbial colonization regulates global histone acetylation and methylation in
      multiple host tissues in a diet-dependent manner: consumption of a "Western-type"
      diet prevents many of the microbiota-dependent chromatin changes that occur in a
      polysaccharide-rich diet. Finally, we demonstrate that supplementation of germ
      free mice with short-chain fatty acids, major products of gut bacterial
      fermentation, is sufficient to recapitulate chromatin modification states and
      transcriptional responses associated with colonization. These findings have
      profound implications for understanding the complex functional interactions
      between diet, gut microbiota, and host health.

PMID- 27889452
TI  - An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences.
AB  - Repetitive genomic regions include tandem sequence repeats and interspersed
      repeats, such as endogenous retroviruses and LINE-1 elements. Repressive
      heterochromatin domains silence expression of these sequences through mechanisms
      that remain poorly understood. Here, we present evidence that the retinoblastoma
      protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit
      enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include
      simple repeats, satellites, LINEs, and endogenous retroviruses as well as
      transposon fragments. We generated a mutant mouse strain carrying an F832A
      mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss
      of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic
      locations and permits repeat expression. Consistent with maintenance of H3K27me3
      at the Hox clusters, these mice are developmentally normal. However,
      susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive
      elements may be cancer relevant.

PMID- 27889453
TI  - Simultaneous Real-Time Imaging of Leading and Lagging Strand Synthesis Reveals
      the Coordination Dynamics of Single Replisomes.
AB  - The molecular machinery responsible for DNA replication, the replisome, must
      efficiently coordinate DNA unwinding with priming and synthesis to complete
      duplication of both strands. Due to the anti-parallel nature of DNA, the leading
      strand is copied continuously, while the lagging strand is produced by repeated
      cycles of priming, DNA looping, and Okazaki-fragment synthesis. Here, we report a
      multidimensional single-molecule approach to visualize this coordination in the
      bacteriophage T7 replisome by simultaneously monitoring the kinetics of loop
      growth and leading-strand synthesis. We show that loops in the lagging strand
      predominantly occur during priming and only infrequently support subsequent
      Okazaki-fragment synthesis. Fluorescence imaging reveals polymerases remaining
      bound to the lagging strand behind the replication fork, consistent with Okazaki
      fragment synthesis behind and independent of the replication complex. Individual
      replisomes display both looping and pausing during priming, reconciling divergent
      models for the regulation of primer synthesis and revealing an underlying
      plasticity in replisome operation.

PMID- 27889454
TI  - The use of molecular dynamics simulations to evaluate the DNA sequence
      selectivity of G-A cross-linking PBD-duocarmycin dimers.
AB  - The pyrrolobenzodiazepine (PBD) and duocarmycin families are DNA-interactive
      agents that covalently bond to guanine (G) and adenine (A) bases, respectively,
      and that have been joined together to create synthetic dimers capable of cross
      linking G-G, A-A, and G-A bases. Three G-A alkylating dimers have been reported
      in publications to date, with defined DNA-binding sites proposed for two of them.
      In this study we have used molecular dynamics simulations to elucidate preferred
      DNA-binding sites for the three published molecular types. For the PBD-CPI dimer
      UTA-6026 (1), our simulations correctly predicted its favoured binding site
      (i.e., 5'-C(G)AATTA-3') as identified by DNA cleavage studies. However, for the
      PBD-CI molecule ('Compound 11', 3), we were unable to reconcile the results of
      our simulations with the reported preferred cross-linking sequence (5'-ATTTTCC(G)
      3'). We found that the molecule is too short to span the five base pairs between
      the A and G bases as claimed, but should target instead a sequence such as 5'
      ATTTC(G)-3' with two less base pairs between the reacting G and A residues. Our
      simulation results for this hybrid dimer are also in accord with the very low
      interstrand cross-linking and in vitro cytotoxicity activities reported for it.
      Although a preferred cross-linking sequence was not reported for the third hybrid
      dimer ('27eS', 2), our simulations predict that it should span two base pairs
      between covalently reacting G and A bases (e.g., 5'-GTAT(A)-3').

PMID- 27889455
TI  - In vivo evaluation of [18F]FECIMBI-36, an agonist 5-HT2A/2C receptor PET
      radioligand in nonhuman primate.
AB  - We recently reported the radiosynthesis and in vitro evaluation of [18F]-2-(4
      bromo-2,5-dimethoxyphenyl)-N-(2-(2-fluoroethoxy)benzyl)ethanamine, ([18F]FECIMBI
      36) or ([18F]1), an agonist radioligand for 5HT2A/2C receptors in postmortem
      samples of human brain. Herein we describe the in vivo evaluation of [18F]FECIMBI
      36 in vervet/African green monkeys by PET imaging. PET images show that
      [18F]FECIMBI-36 penetrates the blood-brain barrier and a low retention of
      radioactivity is observed in monkey brain. Although the time activity curves
      indicate a somehow heterogeneous distribution of the radioligand in the brain,
      the low level of [18F]FECIMBI-36 in brain may limit the use of this tracer for
      quantification of 5-HT2A/2C receptors by PET.

PMID- 27889456
TI  - Synthesis of new morpholine-connected pyrazolidine derivatives and their
      antimicrobial, antioxidant, and cytotoxic activities.
AB  - A simple and convenient one-pot four-component synthesis of morpholine-connected
      pyrazolidine derivatives 2a-f and 4a-f was developed using direct metal-free
      catalysis, with the identities of the synthesized compounds confirmed by IR, NMR
      (1H and 13C), mass spectrometry, and elemental analysis. The prepared compounds
      were inspected for antimicrobial, antioxidant, and cytotoxic activities.
      Antimicrobial and antifungal activities against five bacterial and four fungal
      pathogens, respectively, were investigated using the disc diffusion technique. In
      antibacterial activity, compounds 2d and 2f (MIC=2MUg/mL) exhibited significantly
      higher activity than the standard ciprofloxacin. The results of antifungal assay
      showed that the activity of compound 4a (MIC=0.5MUg/mL) was significantly higher
      than the standard clotrimazole. Antioxidant activity was screened based on ABTS+
      radical scavenging and linoleic acid peroxidation performance. Compound 4a showed
      substantial antioxidant (91.3%) activities, as compared with the Trolox standard.
      Cytotoxicity was evaluated using HepG2 (liver), HeLa (cervical), and MCF-7
      (breast) cancer cell lines, with high toxicities observed for 2b (GI50=12.2MUm)
      and 4a (GI50=07.8MUm).

PMID- 27889457
TI  - A study of oxidative stress and the newer antiepileptic drugs in epilepsy
      associated with severe motor and intellectual disabilities.
AB  - BACKGROUND: Patients with severe motor and intellectual disabilities (SMID) are
      those who have both severe intellectual disabilities and severe physical
      disabilities. Intractable epilepsy is often associated with SMID. The purpose of
      this study was to elucidate the relationship between epilepsy associated with
      SMID and oxidative stress, and to clarify the safety and efficacy of the newer
      antiepileptic drugs (newer AEDs), lamotrigine and levetiracetam. METHODS: This
      study was conducted in 27 SMID patients with epilepsy who were treated with the
      newer AEDs. The patient characteristics and the safety and efficacy of the newer
      AEDs were investigated. The reactive oxygen metabolite (d-ROM) and biological
      antioxidant potential (BAP) levels were measured as indicators of the degree of
      oxidative stress. The relationship between the investigation results (the patient
      characteristics, and the safety and efficacy of the newer AEDs) and the results
      of measurements of the d-ROMs/BAP were analyzed. RESULTS: All the patients who
      discontinued the newer AEDs had abnormal plasma d-ROM levels. In addition, all
      the patients who developed adverse events also had abnormal d-ROM levels.
      Furthermore, there was a trend toward a lower response rate in patients with
      higher plasma d-ROM levels. CONCLUSION: The results of this study suggested that
      d-ROM levels are useful for predicting the safety and efficacy of the newer AEDs
      (lamotrigine, levetiracetam) in SMID patients with intractable epilepsy.
      Therefore, d-ROMs could be important biomarkers for determining the safety and
      efficacy of drug therapy in SMID patients with epilepsy.

PMID- 27889458
TI  - Transcatheter device closure of postmyocardial infarction ventricular septal
      defect.
AB  - BACKGROUND: Transcatheter device closure of postmyocardial infarction ventricular
      septal defect (PMIVSD) is less invasive than surgical repair. However, its
      feasibility, timing, outcome, and prognostic factors remain unclear. METHODS:
      This was a multicenter, retrospective cohort study. Between February 2012 and
      July 2015, a total of 10 (8 male and 2 female) patients with PMIVSD undergoing
      attempted device closure were enrolled retrospectively. The procedures were
      performed under general anesthesia with fluoroscopic and transesophageal
      echocardiographic guidance. RESULTS: The patients enrolled in the study were in
      the age range 50-85 years (median age of 76.5 years). The interval from
      infarction to device closure ranged from 6-147 days, with the median of 12 days.
      A total of 13 devices were implanted in 10 patients. There were five Amplatzer
      muscular ventricular septal defect occluders, four Amplatzer septal occluders,
      three Amplatzer PMIVSD occluders and one Amplatzer vascular plug II.
      Complications included transient ventricular tachycardia in three patients,
      device embolization in one patient, and tracheal bleeding in one patient. No
      procedure-related death, stroke, or cardiac tamponade was noted. During follow
      up, two patients died of heart failure and two patients died of sepsis. Overall,
      subjects with age >= 80 years, systolic blood pressure <= 90 mmHg, and procedure
      time >=180 minutes were significant predictor factors for mortality. All patients
      with the interval of infarction to device closure >12 days survived. CONCLUSION:
      Our findings indicate that transcatheter device closure of PMIVSD is technically
      feasible, safe, and effective to reduce the shunt. The crucial prognostic factors
      were ascertained to be age >= 80 years, systolic blood pressure <= 90 mmHg, and
      procedure time >=180 minutes.

PMID- 27889460
TI  - Evaluation of time lapse for establishing distal tubal occlusion diagnosis during
      hysterosalpingography procedure performed by using water soluble contrast media.
AB  - BACKGROUND: Hysterosalpingography (HSG) is the most frequently used diagnostic
      measure for simultaneously determining uterine abnormalities and tubal status
      among subfertile women. Despite several broader advantages such as availability
      and increased experience, the subjectivity involved during administration of the
      HSG procedure itself, and necessary imaging review, decreases the reliability and
      accuracy of HSG. In this study, we evaluated the time intervals between X-ray
      imaging during HSG procedure to establish the presence of distal tubal occlusion.
      METHODS: Our study evaluated the HSG records of 89 women who underwent diagnostic
      laparoscopy for infertility work-up. Patients who were diagnosed with distal
      tubal occlusion upon receiving HSG and patients who demonstrated tubal patency on
      HSG were included in the study, to compare the time intervals in seconds from the
      tubal visualization view to the last fluoroscopic X-ray shot during the HSG
      procedure with tubal patency on diagnostic laparoscopy. RESULTS: A statistically
      significant correlation regarding tubal patency between HSG procedures and
      diagnostic laparoscopy chromopertubation procedures was demonstrated. Although
      nearly statistically significant, the interval in seconds between the first HSG
      imaging and distal tubal filling was shorter for patients with patent tubes on
      diagnostic laparoscopy than patients with bilateral tubal occlusion (8.4+/-31.9
      and 12.0+/-19.7, respectively; p=0.057). Time period intervals between the first
      and the last HSG, and between distal tubal filling to the last HSG of patients
      with patent tubes on diagnostic laparoscopy and patients with bilateral distal
      tubal occlusion were found to be statistically similar. CONCLUSION: Although a
      trend exists towards shorter time period intervals between the first uterine
      visualization and distal tubal filling graphy among patients with tubal patency,
      rather than patients with distal tubal occlusion confirmed by diagnostic
      laparoscopy, clinically reliable objective time period intervals for finalizing
      the HSG procedure and proceeding with diagnostic laparoscopy due to distal tubal
      occlusion diagnosis on HSG could not be detected.

PMID- 27889459
TI  - Effect of music on level of anxiety in patients undergoing colonoscopy without
      sedation.
AB  - BACKGROUND: Listening to music can be a noninvasive method for reducing the
      anxiety level without any adverse effects. The aim of this study was to explore
      whether music can reduce anxiety and to compare two different styles of music,
      informal classical music and light music, to ascertain the more effective style
      of music in reducing anxiety in patients undergoing colonoscopy without sedation.
      METHODS: This study enrolled 138 patients who underwent colonoscopy without
      sedation during a general health examination from February 2009 to January 2015.
      The patients were randomly assigned to a group that did not listen to music, a
      group that listened to music by David Tolley, or a group that listened to music
      by Kevin Kern. The State-Trait Anxiety Inventory was used to evaluate the status
      of anxiety. RESULTS: A trend test for mild anxiety was performed on the patients
      in the three groups, and a significant trend was noted (p=0.017 for all patients;
      p=0.014 for analysis by sex). Multivariate analysis for mild anxiety on the
      patients in each group was also performed in this study, and music by Kevin Kern
      was found to have the lowest odds ratio (Odds ratio=0.34, p=0.045). CONCLUSION:
      Listening to music, especially music by Kevin Kern, reduced the level of anxiety
      in patients undergoing colonoscopy examination without sedation.

PMID- 27889461
TI  - Intralesional curettage of central low-grade chondrosarcoma: A midterm follow-up
      study.
AB  - BACKGROUND: The aim of this study was to review the experience of surgical
      treatment of low-grade chondrosarcoma and to assess the long-term oncological and
      functional outcomes between intralesional curettage and wide excision. METHODS:
      We included 11 patients with central low-grade chondrosarcoma lesions treated
      with intralesional curettage or wide excision from 1998 to 2013. Seven patients
      were treated with intralesional curettage and local adjuvant treatment (Group A),
      and four patients were treated with wide excision and reconstructive surgery
      (Group B). The mean age of patients was 43.8+/-17.6 years (range, 20-71 years),
      and the mean duration of follow-up was 84.4+/-47.6 months (range, 48-194 months).
      RESULTS: Group A had a significantly lower complication rate than Group B; three
      complications were documented in Group B (0% vs. 75%, p=0.024). The operative
      time (177.1 hours vs. 366.3 hours, p=0.010) and the hospital stay (6.6 days vs.
      12.5 days, p=0.010) were significantly shorter in Group A. There was one local
      recurrence in Group A without statistical significance. Also, there were no
      differences between intralesional curettage and wide excision with respect to the
      blood loss. No metastasis disease occurred in either group during the follow-up
      period. The Musculoskeletal Tumor Society (MSTS) scores in Groups A and B were
      99.0+/-2.5 and 94.2+/-4.2, respectively, with statistically significant
      difference (p=0.048). CONCLUSION: Extended intralesional curettage has the
      benefits of good MSTS score, shorter operative time, shorter hospital stay, and
      lower complication rate without increasing local recurrence in central low-grade
      chondrosarcoma. For central low-grade chondrosarcoma, we suggest extended
      curettage to decrease soft tissue damage and surgical risk.

PMID- 27889462
TI  - Maternal and umbilical cord blood levels of mercury, manganese, iron, and copper
      in southern Taiwan: A cross-sectional study.
AB  - BACKGROUND: The effect of maternal exposure to essential minerals and heavy
      metals on fetus is an important issue, which affects women around the world. Few
      data are available on the concentration of both essential minerals and heavy
      metals in maternal/fetal medicine. The aims of this study were to (1) assess the
      correlation of mercury (Hg), manganese (Mn), iron (Fe), and copper (Cu) in paired
      maternal/fetal blood samples, and (2) study potential confounding factors during
      pregnancy. METHODS: Our study recruited 145 healthy pregnant women with a mean
      age of 28.06 years, gathering information by collecting interviewer-administered
      questionnaires. Paired maternal/fetal blood samples were collected by delivery.
      RESULTS: There was a positive correlation of Hg (r = 0.78, p<0.001), Mn (r =
      0.31, p<0.001), Fe (r = 0.17, p = 0.038), and Cu (r = 0.21, p = 0.010) in paired
      maternal/fetal samples. Prenatal vitamin use (>3 times/wk) was significantly
      associated with lower maternal Hg (adjusted odds ratio 0.272, p = 0.005) and
      lower maternal Cu (adjusted odds ratio 0.267, p = 0.004) levels. Median fetal Hg,
      Mn, and Fe levels were higher than corresponding maternal levels, while median
      fetal Cu level was lower than maternal Cu level. CONCLUSION: There was a positive
      correlation of Hg, Fe, Cu, and Mn in paired maternal/fetal samples in this
      series. Our findings have raised the possibility of reducing maternal Hg and Cu
      by way of prenatal vitamin supplementation.

PMID- 27889463
TI  - Noncanonical Fungal Autophagy Inhibits Inflammation in Response to IFN-gamma via
      DAPK1.
AB  - Defects in a form of noncanonical autophagy, known as LC3-associated phagocytosis
      (LAP), lead to increased inflammatory pathology during fungal infection. Although
      LAP contributes to fungal degradation, the molecular mechanisms underlying LAP
      mediated modulation of inflammation are unknown. We describe a mechanism by which
      inflammation is regulated during LAP through the death-associated protein kinase
      1 (DAPK1). The ATF6/C/EBP-beta/DAPK1 axis activated by IFN-gamma not only
      mediates LAP to Aspergillus fumigatus but also concomitantly inhibits Nod-like
      receptor protein 3 (NLRP3) activation and restrains pathogenic inflammation. In
      mouse models and patient samples of chronic granulomatous disease, which exhibit
      defective autophagy and increased inflammasome activity, IFN-gamma restores
      reduced DAPK1 activity and dampens fungal growth. Additionally, in a cohort of
      hematopoietic stem cell-transplanted patients, a genetic DAPK1 deficiency is
      associated with increased inflammation and heightened aspergillosis
      susceptibility. Thus, DAPK1 is a potential drugable player in regulating the
      inflammatory response during fungal clearance initiated by IFN-gamma.

PMID- 27889464
TI  - Enterocyte Purge and Rapid Recovery Is a Resilience Reaction of the Gut
      Epithelium to Pore-Forming Toxin Attack.
AB  - Besides digesting nutrients, the gut protects the host against invasion by
      pathogens. Enterocytes may be subjected to damage by both microbial and host
      defensive responses, causing their death. Here, we report a rapid epithelial
      response that alleviates infection stress and protects the enterocytes from the
      action of microbial virulence factors. Intestinal epithelia exposed to hemolysin,
      a pore-forming toxin secreted by Serratia marcescens, undergo an evolutionarily
      conserved process of thinning followed by the recovery of their initial thickness
      within a few hours. In response to hemolysin attack, Drosophila melanogaster
      enterocytes extrude most of their apical cytoplasm, including damaged organelles
      such as mitochondria, yet do not lyse. We identify two secreted peptides, the
      expression of which requires CyclinJ, that mediate the recovery phase in which
      enterocytes regain their original shape and volume. Epithelial thinning and
      recovery constitute a fast and efficient response to intestinal infections, with
      pore-forming toxins acting as alarm signals.

PMID- 27889465
TI  - The role of oxytocin in modulating interpersonal space: A pharmacological fMRI
      study.
AB  - Interpersonal space is a nonverbal indicator of affiliation and closeness. In
      this study we investigated the effects of oxytocin (OT), a neuropeptide known for
      its social role in humans, on interpersonal space. In a double blind placebo
      controlled study we measured the effect of intranasal OT on the personal distance
      preferences of different familiar (friend) and unfamiliar (stranger)
      protagonists. Behavioral results showed that participants preferred to be closer
      to a friend than to a stranger. Intranasal OT was associated with an overall
      distancing effect, but this effect was significant for the stranger and not for
      the friend. The imaging results showed interactions between treatment (OT,
      placebo) and protagonist (friend, stranger) in regions that mediate social
      behavior including the dorsomedial prefrontal cortex (dmPFC), a region associated
      with the mentalizing system. Specifically, OT increased activity in the dmPFC
      when a friend approached the participants but not when a stranger approached. The
      results indicate that the effect of OT on interpersonal space greatly depends on
      the participant's relationship with the protagonist. This supports the social
      salience theory, according to which OT increases the salience of social cues
      depending on the context.

PMID- 27889466
TI  - Lower cortisol level in response to a psychosocial stressor in young females with
      self-harm.
AB  - BACKGROUND: Self-harm is highly prevalent in adolescence, often serving an
      emotion regulation function. Social stressors such as bullying are associated
      with self-harm. The neurobiological background of the relationship between social
      stressors and self-harm needs to be further understood to inform prevention and
      therapy. METHODS: Participants were members of an epidemiological cohort study.
      130 female participants underwent the Trier Social Stress Test (TSST) at age 19.
      Of them, 21 reported a history of self-harm as assessed by the Youth Self Report.
      Psychiatric diagnoses were recorded. RESULTS: Participants with a history of self
      harm showed significantly lower blood cortisol levels throughout the TSST. Early
      psychosocial adversity did not significantly differ between groups with and
      without self-harm, with self-harming participants reporting more childhood
      adversities. CONCLUSION: These results add to the limited field of studies
      showing an altered HPA axis activity in females with self-harm. Future studies
      need to address the causal mechanisms behind this association.

PMID- 27889467
TI  - Treadmill exercise decreases amyloid-beta burden possibly via activation of SIRT
      1 signaling in a mouse model of Alzheimer's disease.
AB  - Accumulation of amyloid-beta (Abeta) correlates significantly with progressive
      cognitive deficits, a main symptom of Alzheimer's disease (AD). Although
      treadmill exercise reduces Abeta levels, the molecular mechanisms underlying the
      effects are not fully understood. We hypothesize that treadmill exercise
      decreases Abeta production and alleviates cognitive deficits by activating the
      non-amyloidogenic pathway via SIRT-1 signaling. Treadmill exercise improved
      cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill
      exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10
      level by down-regulation of ROCK-1 and upregulation of RARbeta, ultimately
      facilitating the non-amyloidogenic pathway. Treadmill exercise-induced activation
      in SIRT-1 level also elevated PGC-1alpha level and reduced BACE-1 and C-99 level,
      resulting in inhibition of the amyloidogenic pathway. Treadmill exercise may thus
      inhibit Abeta production via upregulation of SIRT-1, which biases amyloid
      precursor protein processing toward the non-amyloidogenic pathway. This study
      provides novel and valuable insight into the molecular mechanisms possibly by
      which treadmill exercise reduces Abeta production.

PMID- 27889468
TI  - Mitochondrial cristae remodelling is associated with disrupted OPA1
      oligomerisation in the Huntington's disease R6/2 fragment model.
AB  - There is evidence of an imbalance of mitochondrial fission and fusion in patients
      with Huntington's disease (HD) and HD animal models. Fission and fusion are
      important for mitochondrial homeostasis including mitochondrial DNA (mtDNA)
      maintenance and may be relevant for the selective striatal mtDNA depletion that
      we observed in the R6/2 fragment HD mouse model. We aimed to investigate the
      fission/fusion balance and the integrity of the mitochondrial membrane system in
      cortex and striatum of end-stage R6/2 mice and wild-type animals. Mitochondrial
      morphology was determined using electron microscopy, and transcript and protein
      levels of factors that play a key role in fission and fusion, including DRP1,
      mitofusin 1 and 2, mitofilin and OPA1, and cytochrome c and caspase 3 were
      assessed by RT-qPCR and immunoblotting. OPA1 oligomerisation was evaluated using
      blue native gels. In striatum and cortex of R6/2 mice, mitochondrial cristae
      morphology was abnormal. Mitofilin and the overall levels of the fission and
      fusion factors were unaffected; however, OPA1 oligomerisation was abnormal in
      striatum and cortex of R6/2 mice. Mitochondrial and cytoplasmic cytochrome c
      levels were similar in R6/2 and wild-type mice with no significant increase of
      activated caspase 3. Our results indicate that the integrity of the mitochondrial
      cristae is compromised in striatum and cortex of the R6/2 mice and that this is
      most likely caused by impaired OPA1 oligomerisation.

PMID- 27889469
TI  - Changes in neural circuitry associated with depression at pre-clinical, pre-motor
      and early motor phases of Parkinson's disease.
AB  - Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can
      present at early stages as a non-motor pathology. Among the non-motor clinical
      manifestations, depression shows a high prevalence and can be one of the first
      clinical signs to appear, even a decade before the onset of motor symptoms. Here,
      we review the evidence of early dysfunction in neural circuitry associated with
      depression in the context of PD, focusing on pre-clinical, pre-motor and early
      motor phases of the disease. In the pre-clinical phase, structural and functional
      changes in the substantia nigra, basal ganglia and limbic structures are already
      observed. Some of these changes are linked to motor compensation mechanisms while
      others correspond to pathological processes common to PD and depression and thus
      could underlie the appearance of depressive symptoms during the pre-motor phase.
      Studies of the early motor phase (less than five years post diagnosis) reveal an
      association between the extent of damage in different monoaminergic systems and
      the appearance of emotional disorders. We propose that the limbic loop of the
      basal ganglia and the lateral habenula play key roles in the early genesis of
      depression in PD. Alterations in the neural circuitry linked with emotional
      control might be sensitive markers of the ongoing neurodegenerative process and
      thus may serve to facilitate an early diagnosis of this disease. To take
      advantage of this, we need to improve the clinical criteria and develop
      biomarkers to identify depression, which could be used to determine individuals
      at risk to develop PD.

PMID- 27889470
TI  - Delayed administration of dopaminergic drugs is not associated with prolonged
      length of stay of hospitalized patients with Parkinson's disease.
AB  - BACKGROUND: Punctual delivery of dopaminergic medication to Parkinson's disease
      (PD) patients may be important in optimizing disease control. We tested the
      hypothesis that prompt delivery of l-dopa medications to emergency hospital
      inpatients was associated with a decreased length of stay in hospital. METHODS:
      The study population consisted of all urgent hospitalizations for patients with a
      diagnosis of PD to the Royal Derby Hospital over a two-year period. Data were
      extracted on timing of delivery of drugs, number of co-morbidities and length of
      stay. Statistical analysis used linear regression adjusting for within admission
      clustering. RESULTS: 431 individuals provided data from a total of 737
      admissions. 39% of scheduled l-dopa doses were either not given or administered
      over 30 min later than the scheduled time. There was no association between the
      omission or timing of a dose of PD medication and length of stay in hospital. The
      number of coded diagnoses was strongly associated with length of stay with a dose
      response association (pTREND<0.001). Those with 10 concurrent diagnoses had a 11
      day longer stay (95% confidence intervals: +2 to +21) than those with no
      comorbidities. CONCLUSIONS: Delayed administration of dopaminergic drugs is not
      associated with prolonged length of stay of in patients with PD who were admitted
      to hospital as an emergency. However, the number of co-existing medical diagnoses
      was associated with length of stay, and early attention to these has the
      potential to improve patient care and decrease length of stay in hospital.

PMID- 27889471
TI  - Functional characterization of two naturally occurring mutations V221G and T449N
      in the follicle stimulating hormone receptor.
AB  - Naturally occurring mutations in follicle stimulating hormone receptor (FSHR)
      affect the receptor function. Here, we characterized two such previously reported
      mutations, V221G and T449N, in the extracellular domain and transmembrane helix
      3, of FSHR, respectively. Functional studies with the V221G mutant demonstrated
      an impairment in FSH binding and signaling. Validation of X-ray crystallography
      data indicating the contribution of FSHR specific residues in the vicinity of
      V221 to contribute to FSH-FSHR interaction was carried out. In vitro mutational
      studies showed that these residues are determinants of both FSH binding and FSH
      induced signaling. Analysis of the T449N mutation revealed that it results in an
      increase in FSH binding and high cAMP response at lower doses of FSH. A marginal
      hCG induced and no TSH induced cAMP production was also observed. These findings
      corroborated with the clinical manifestations of primary amenorrhea (V221G) and
      spontaneous ovarian hyperstimulation syndrome (T449N) in women harbouring these
      mutations.

PMID- 27889473
TI  - Endothelial cells regulate beta-catenin activity in adrenocortical cells via
      secretion of basic fibroblast growth factor.
AB  - Endothelial cell-derived products influence the synthesis of aldosterone and
      cortisol in human adrenocortical cells by modulating proteins such as
      steroidogenic acute-regulatory (StAR) protein, steroidogenic factor (SF)-1 and
      CITED2. However, the potential endothelial cell-derived factors that mediate this
      effect are still unknown. The current study was perfomed to look into the control
      of beta-catenin activity by endothelial cell-derived factors and to identify a
      mechanism by which they affect beta-catenin activity in adrenocortical NCIH295R
      cells. Using reporter gene assays and Western blotting, we found that endothelial
      cell-conditioned medium (ECCM) led to nuclear translocation of beta-catenin and
      an increase in beta-catenin-dependent transcription that could be blocked by
      U0126, an inhibitor of the mitogen-activated protein kinase pathway. Furthermore,
      we found that a receptor tyrosin kinase (RTK) was involved in ECCM-induced beta
      catenin-dependent transcription. Through selective inhibition of RTK using
      Su5402, it was shown that receptors responding to basic fibroblast growth factor
      (bFGF) mediate the action of ECCM. Adrenocortical cells treated with bFGF showed
      a significant greater level of bFGF mRNA. In addition, HUVECs secrete bFGF in a
      density-dependent manner. In conclusion, the data suggest that endothelial cells
      regulate beta-catenin activity in adrenocortical cells also via secretion of
      basic fibroblast growth factor.

PMID- 27889472
TI  - Comprehensive assessment of estrogen receptor beta antibodies in cancer cell line
      models and tissue reveals critical limitations in reagent specificity.
AB  - Estrogen Receptor-beta (ERbeta) has been implicated in many cancers. In prostate
      and breast cancer its function is controversial, but genetic studies implicate a
      role in cancer progression. Much of the confusion around ERbeta stems from
      antibodies that are inadequately validated, yet have become standard tools for
      deciphering its role. Using an ERbeta-inducible cell system we assessed commonly
      utilized ERbeta antibodies and show that one of the most commonly used
      antibodies, NCL-ER-BETA, is non-specific for ERbeta. Other antibodies have
      limited ERbeta specificity or are only specific in one experimental modality.
      ERbeta is commonly studied in MCF-7 (breast) and LNCaP (prostate) cancer cell
      lines, but we found no ERbeta expression in either, using validated antibodies
      and independent mass spectrometry-based approaches. Our findings question
      conclusions made about ERbeta using the NCL-ER-BETA antibody, or LNCaP and MCF-7
      cell lines. We describe robust reagents, which detect ERbeta across multiple
      experimental approaches and in clinical samples.

PMID- 27889474
TI  - The Von Willebrand Factor A1-Collagen III Interaction Is Independent of
      Conformation and Type 2 Von Willebrand Disease Phenotype.
AB  - The blood von Willebrand factor (VWF) mediates platelet adhesion to injured
      vessels by sequestering platelets from blood flow and depositing them to collagen
      and other exposed subendothelial matrix proteins. This process of capturing
      platelets to facilitate formation of platelet plugs occurs through transient
      interactions with platelet glycoprotein Ibalpha via the VWF A1 domain which also
      binds collagen. Using a conformationally diverse collection of natively folded
      and mutation-induced misfolded von Willebrand disease (VWD) variants, we test a
      recently proposed affinity up-regulation hypothesis which states that collagen
      binding changes the conformation of the A1 domain to a high-affinity GPIbalpha
      binding competent state. With surface plasmon resonance (SPR), we present this
      diversified collection to collagen and quantify the kinetics of association and
      dissociation to ascertain the conformational selectivity of collagen. With
      analytical rheology, we quantify real-time platelet pause times and translocation
      velocities across a Cu2+ HisTag-chelated and collagen-bound A1 single domain and
      A1A2A3 tridomain fragment of VWF under shear stress in an ex vivo shear flow
      microfluidic chamber. In contrast to expected hypothetical outcomes, collagen has
      limited conformational selectivity for binding A1. A1-collagen binding is
      independent of gain- or loss-of-function phenotype and under shear stress,
      platelet translocation pause times on collagen-bound A1A2A3 are either normal or
      shorter depending on whether A1 is concertedly bound with the A3 domain to
      collagen. With respect to A1, collagen has an inhibitory role that provides an
      explanation for the lack of thrombosis in patients with gain-of-function VWD.

PMID- 27889475
TI  - Reaction engineering analysis of Scenedesmus ovalternus in a flat-plate gas-lift
      photobioreactor.
AB  - Microalgal strains of the genus Scenedesmus are a promising resource for
      commercial biotechnological applications. The temperature-, pH- and light
      dependent growth of Scenedesmus ovalternus has been investigated on a laboratory
      scale. Best batch process performance was obtained at 30 degrees C, pH 8.0 and an
      incident photon flux density of 1300MUmolphotonsm-2s-1 using a flat-plate gas
      lift photobioreactor. Highest growth rate (0.11h-1) and space-time yield (1.7+/
      0.1gCDWL-1d-1) were observed when applying these reaction conditions. Biomass
      concentrations of up to 7.5+/-0.1gCDWL-1 were achieved within six days (25.0+/
      0.5gCDWm-2d-1). The light-dependent growth kinetics of S. ovalternus was
      identified using Schuster's light transfer model and Andrews' light inhibition
      model (KS=545MUmolphotonsm-2s-1; KI=2744MUmolphotonsm-2s-1; MUmax=0.21h-1). The
      optimal mean integral photon flux density for growth of S. ovalternus was
      estimated to be 1223MUmolphotonsm-2s-1.

PMID- 27889476
TI  - Yeast and carbon nanotube based biocatalyst developed by synergetic effects of
      covalent bonding and hydrophobic interaction for performance enhancement of
      membraneless microbial fuel cell.
AB  - Membraneless microbial fuel cell (MFC) employing new microbial catalyst formed as
      yeast cultivated from Saccharomyces cerevisiae and carbon nanotube (yeast/CNT) is
      suggested. To analyze its catalytic activity and performance and stability of
      MFC, several characterizations are performed. According to the characterizations,
      the catalyst shows excellent catalytic activities by facile transfer of electrons
      via reactions of NAD, FAD, cytochrome c and cytochrome a3, while it induces high
      maximum power density (MPD) (344mW.m-2). It implies that adoption of yeast
      induces increases in catalytic activity and MFC performance. Furthermore, MPD is
      maintained to 86% of initial value even after eight days, showing excellent MFC
      stability.

PMID- 27889477
TI  - Levulinic acid production by two-step acid-catalyzed treatment of Quercus
      mongolica using dilute sulfuric acid.
AB  - The objectives of this research were to produce a levulinic acid by two-step acid
      catalyzed treatment of Quercus mongolica and to investigate the effect of
      treatment parameter (reaction temperature range: 100-230 degrees C; sulfuric acid
      (SA) concentration range: 0-2%) on the levulinic acid yield. After 1st step acid
      catalyzed treatment, most of the hemicellulosic C5 sugars (15.6gg/100gbiomass)
      were released into the liquid hydrolysate at the reaction temperature of 150
      degrees C in 1% SA; the solid fraction, which contained 53.5% of the C6 sugars,
      was resistant to further loss of C6 sugars. Subsequently, 2nd step acid-catalyzed
      treatment of the solid fractions was performed under more severe conditions.
      Finally, 16.5g/100g biomass of levulinic acid was produced at the reaction
      temperature of 200 degrees C in 2% SA, corresponding to a higher conversion rate
      than during single-step treatment.

PMID- 27889478
TI  - Sequential enzymatic saccharification and fermentation of ionic liquid and
      organosolv pretreated agave bagasse for ethanol production.
AB  - Agave bagasse (AGB) has gained recognition as a drought-tolerant biofuel
      feedstock with high productivity in semiarid regions. A comparative analysis of
      ionic liquid (IL) and organosolv (OV) pretreatment technologies in AGB was
      performed using a sequential enzymatic saccharification and fermentation (SESF)
      strategy with cellulolytic enzymes and the ethanologenic Escherichia coli strain
      MS04. After pretreatment, 86% of xylan and 45% of lignin were removed from OV
      AGB, whereas IL-AGB reduced lignin content by 28% and xylan by 50% when compared
      to the untreated biomass. High glucan (>90%) and xylan (>83%) conversion was
      obtained with both pretreated samples. During the fermentation stage (48h), 12.1
      and 12.7kg of ethanol were produced per 100kg of untreated AGB for IL and OV,
      respectively. These comparative analyses showed the advantages of SESF using IL
      and OV in a biorefinery configuration where a better understanding of AGB
      recalcitrance is key for future applications.

PMID- 27889479
TI  - IDO1 is an Integral Mediator of Inflammatory Neovascularization.
AB  - The immune tolerogenic effects of IDO1 (indoleamine 2,3-dioxygenase 1) have been
      well documented and genetic studies in mice have clearly established the
      significance of IDO1 in tumor promotion. Dichotomously, the primary inducer of
      IDO1, the inflammatory cytokine IFNgamma (interferon-gamma), is a key mediator of
      immune-based tumor suppression. One means by which IFNgamma can exert an anti
      cancer effect is by decreasing tumor neovascularization. We speculated that IDO1
      might contribute to cancer promotion by countering this anti-neovascular effect
      of IFNgamma, possibly through IDO1-potentiated elevation of the pro-tumorigenic
      inflammatory cytokine IL6 (interleukin-6). In this study, we investigated how
      genetic loss of IDO1 affects neovascularization in mouse models of oxygen-induced
      retinopathy and lung metastasis. Neovascularization in both models was
      significantly reduced in mice lacking IDO1, was similarly reduced with loss of
      IL6, and was restored in both cases by concomitant loss of IFNgamma. Likewise,
      the lack of IDO1 or IL6 resulted in reduced metastatic tumor burden and increased
      survival, which the concomitant loss of IFNgamma abrogated. This insight into
      IDO1's involvement in pro-tumorigenic inflammatory neovascularization may have
      important ramifications for IDO1 inhibitor development, not only in cancer where
      clinical trials are currently ongoing, but in other disease indications
      associated with neovascularization as well.

PMID- 27889480
TI  - Therapeutic Manipulation of Ageing: Repurposing Old Dogs and Discovering New
      Tricks.
AB  - Ageing is a leading risk factor for many debilitating diseases. While age-related
      diseases have been the subject of over a century of intense investigation, until
      recently, physiological ageing was considered unavoidable. Pharmacological and
      genetic studies have since shown that ageing is a malleable process and that its
      abrogation can prevent its associated diseases. This review summarises a sample
      of the most promising efforts to deliver the products of ageing research to the
      clinic. Current efforts include the use of clinically approved drugs that have
      since been repurposed, as well as the development of novel therapeutics, to
      target ageing. Furthermore, ongoing research has sought reliable biomarkers of
      ageing that will accelerate the development of such therapeutics. Development of
      these technologies will improve quality of late-life and help relieve the
      enormous stress placed on state healthcare systems by a rapidly ageing global
      population. Thus, for both medical and socioeconomic reasons, it is imperative
      that ageing is made to yield to intervention.

PMID- 27889481
TI  - Mitotic Nuclear Envelope Breakdown and Spindle Nucleation Are Controlled by
      Interphase Contacts between Centromeres and the Nuclear Envelope.
AB  - Faithful genome propagation requires coordination between nuclear envelope (NE)
      breakdown, spindle formation, and chromosomal events. The conserved linker of
      nucleoskeleton and cytoskeleton (LINC) complex connects fission yeast centromeres
      and the centrosome, across the NE, during interphase. During meiosis, LINC
      connects the centrosome with telomeres rather than centromeres. We previously
      showed that loss of telomere-LINC contacts compromises meiotic spindle formation.
      Here, we define the precise events regulated by telomere-LINC contacts and
      address the analogous possibility that centromeres regulate mitotic spindle
      formation. We develop conditionally inactivated LINC complexes in which the
      conserved SUN-domain protein Sad1 remains stable but severs interphase centromere
      LINC contacts. Strikingly, the loss of such contacts abolishes spindle formation.
      We pinpoint the defect to a failure in the partial NE breakdown required for
      centrosome insertion into the NE, a step analogous to mammalian NE breakdown.
      Thus, interphase chromosome-LINC contacts constitute a cell-cycle control device
      linking nucleoplasmic and cytoplasmic events.

PMID- 27889483
TI  - Classification, surgical management and outcomes of patients with gastrogastric
      fistula after Roux-En-Y gastric bypass.
AB  - BACKGROUND: Gastrogastric fistula (GGF) is a known complication after Roux-en-Y
      gastric bypass that can lead to marginal ulceration (MU) and failure of weight
      loss. OBJECTIVES: To describe our experience with GGF management and propose a
      classification of GGF based on its anatomic location. SETTING: University
      hospital, France. METHODS: After internal review board approval, data from all
      patients with a GGF were reviewed. GGF was classified as type 1 when located in
      the proximal part of the gastric pouch and type 2 when located near the
      gastrojejunostomy. RESULTS: Nine patients developed a GGF (.5%). GGF symptoms
      included epigastric pain (78%), vomiting (11%), gastrointestinal bleeding (11%),
      and weight regain (44%). Upper contrast study identified GGF in all patients.
      Upper endoscopy confirmed GGF in 6 patients, all with type 2. Eight patients
      required revisional surgery. Patients with type 1 GGF (n = 3) had excision of the
      fistulous tract. Patients with type 2 GGF (n = 5) had associated revision of the
      gastrojejunostomy. Mean operative time was significantly longer for type 2 GGF.
      The mean follow-up was 43 months, with no patient lost. One patient developed a
      recurrent MU requiring iterative revision. After that, all revisional patients
      were symptom free and the mean body mass index was 35.3+/-9.5 kg/m2. CONCLUSION:
      Weight regain and epigastric pain with or without associated MU are the most
      common signs of GGF. Combining upper gastrointestinal endoscopy and contrast
      study is the best method to confirm the diagnosis. Surgical treatment should be
      tailored to both GGF location and status of the gastrojejunostomy. Based on its
      anatomic location, GGF classification could serve as a working basis to compare
      different surgical approaches.

PMID- 27889482
TI  - The Red Light Receptor Phytochrome B Directly Enhances Substrate-E3 Ligase
      Interactions to Attenuate Ethylene Responses.
AB  - Plants germinating under subterranean darkness assume skotomorphogenesis, a
      developmental program strengthened by ethylene in response to mechanical pressure
      of soil. Upon reaching the surface, light triggers a dramatic developmental
      transition termed de-etiolation that requires immediate termination of ethylene
      responses. Here, we report that light activation of photoreceptor phyB results in
      rapid degradation of EIN3, the master transcription factor in the ethylene
      signaling pathway. As a result, light rapidly and efficiently represses ethylene
      actions. Specifically, phyB directly interacts with EIN3 in a light-dependent
      manner and also physically associates with F box protein EBFs. The light
      activated association of phyB, EIN3, and EBF1/EBF2 proteins stimulates robust
      EIN3 degradation by SCFEBF1/EBF2 E3 ligases. We reveal that phyB manipulates
      substrate-E3 ligase interactions in a light-dependent manner, thus directly
      controlling the stability of EIN3. Our findings illustrate a mechanistic model of
      how plants transduce light information to immediately turn off ethylene signaling
      for de-etiolation initiation.

PMID- 27889484
TI  - Refractory pseudoachalasia secondary to laparoscopically placed adjustable
      gastric band successfully treated with Heller myotomy.

PMID- 27889485
TI  - Safety and effectiveness of anterior fundoplication sleeve gastrectomy in
      patients with severe reflux.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy has become a popular bariatric
      surgery in recent years. However, it has been linked to worsening or newly
      developed gastroesophageal reflux disease (GERD) in the postoperative period.
      OBJECTIVES: The purpose of this study is to determine the safety and
      effectiveness of anterior fundoplication sleeve gastrectomy in patients with
      reflux. SETTING: Academic hospital, United States. METHODS: We prospectively
      collected data on 31 sleeve gastrectomy patients who concurrently underwent
      anterior fundoplication between July 2014 and March 2016. Patients were selected
      when they reported severe reflux before the procedure. Each patient was
      interviewed using the GERD score questionnaire (scaled severity and frequency of
      heartburn, regurgitation, epigastric pain, epigastric fullness, dysphagia, and
      cough) before and 4 months after the procedure. RESULTS: Our patients comprised
      27 females and 4 males with a mean age of 49.9+/-9.6 years (range, 29-63 yr).
      They had a mean preoperative body mass index of 42.8+/-5.6 kg/m2 (range, 33.3
      58.4 kg/m2), and 67.7% (n = 21) of these patients underwent hiatal hernia repair
      as well. Preoperatively, patients had a mean heartburn score of 7.4+/-3.6 (range,
      1-12), regurgitation score of 5.4+/-4.1 (range, 0-12), epigastric pain score of
      2.1+/-3.2 (range, 0-12), epigastric fullness score of 2.7+/-3.9 (range, 0-12),
      dysphagia score of 1.3+/-2.2 (range, 0-9), and cough score of .9+/-1.8 (range, 0
      6). Mean preoperative GERD score was 18.9+/-9.8 (range, 6-36) in these patients.
      Patients were interviewed with the same questionnaire approximately 4 months
      postoperative. Patients had a mean heartburn score of 1.5+/-3.2 (range, 0-12),
      regurgitation score of .9+/-1.7 (range, 0-8), epigastric pain score of .4+/-1.1
      (range, 0-4), epigastric fullness score of 1.1+/-2.4 (range, 0-8), dysphagia
      score of .3+/-1.1 (range, 0-6), and cough score of 0. Mean postoperative GERD
      score dropped down to 4.1+/-5.8 (range, 0-28), and the difference was
      statistically significant (P<.01). One patient was readmitted 28 days later for a
      staple line leakage, and was treated conservatively. No patient required a
      reoperation due to the procedure within 30 days. CONCLUSION: Anterior
      fundoplication sleeve gastrectomy may be a safe and effective alternative in
      obese patients with severe reflux who want to undergo sleeve gastrectomy.

PMID- 27889486
TI  - Abdominoplasty with Scarpa fascia preservation - comparative study in a bariatric
      population.
AB  - BACKGROUND: Abdominoplasty techniques using a more superficial plane of
      dissection with Scarpa fascia preservation have been shown to improve recovery
      and reduce complications in nonbariatric patients. Patients who have experienced
      massive weight loss frequently need body contour procedures and represent a high
      risk group. OBJECTIVE: To evaluate the effect of this technique in patients with
      massive weight loss after bariatric surgery. SETTING: University hospital,
      Portugal. METHODS: This was a single-center retrospective study of 51
      postbariatric patients who had been undergone either a classic full
      abdominoplasty (group A) or a similar procedure except for the preservation of
      Scarpa fascia below the umbilicus (group B). General characteristics of both
      groups were analyzed, and recorded outcomes were total and daily volume of drain
      output, time until drain removal, time until hospital discharge, and local and
      systemic complications. RESULTS: There were no statistically significant
      differences between groups regarding general characteristics or complications.
      The Scarpa fascia preservation group had a highly significant reduction of 79% on
      the total drain output, 7 days until drain removal, and 5 days' hospital stay.
      Long drainers (7 days or more with drains) were eliminated (reduction from 52% in
      group A to 3% in group B) and seroma had a 65% reduction. CONCLUSION: Preserving
      Scarpa fascia during a full abdominoplasty in postbariatric patients improves
      recovery by reducing total drain output and hospital stay, allowing earlier drain
      removal, eliminating long periods with suction drains, and reducing seroma
      incidence. Clear benefits for the patient were obtained.

PMID- 27889487
TI  - ADHD severity as it relates to comorbid psychiatric symptomatology in children
      with Autism Spectrum Disorders (ASD).
AB  - Comorbid diagnoses identified in pediatric samples have been correlated with a
      range of outcomes, including greater levels of emotional, behavioral, and
      educational impairment and the need for more intensive treatment. Given that
      previous research has documented high levels of comorbid Attention
      Deficit/Hyperactivity Disorder (ADHD) in children with Autism Spectrum Disorders
      (ASD), this study closely examines the relationship between parent-reported ADHD
      symptoms (i.e., Conners' Parent Rating Scale, Revised [CPRS-R]) and the
      prevalence of additional comorbid psychiatric diagnoses in a pediatric ASD sample
      (n=99). Regression analyses revealed that greater severity of ADHD symptomatology
      was significantly related to a greater number of comorbid psychiatric diagnoses,
      as identified using the Diagnostic Interview for Children and adolescents, 4th
      Edition (DICA-IV). Additionally, more severe ADHD symptoms were also associated
      with higher levels of symptom severity on Child Behavior Checklist (CBCL)
      syndrome subscales. Interestingly, increasing severity of ASD symptomatology, as
      measured by the Autism Diagnostic Interview, Revised (ADI-R), was not associated
      with a higher prevalence of comorbid psychiatric diagnoses or CBCL syndrome
      severity. Our study concluded that higher levels of ADHD severity-not ASD
      severity-were associated with a higher prevalence of comorbid psychiatric
      symptomatology in school-age children with ASD. These findings may encourage
      clinicians to thoroughly assess ADHD symptomatology in ASD children to better
      inform treatment planning.

PMID- 27889488
TI  - Enhanced LTP in aged rats: Detrimental or compensatory?
AB  - Age-dependent memory deterioration has been well documented and yet an increase
      in rat hippocampal LTP upon aging has been reported. This poses the question of
      whether the enhanced LTP is a cause or an attempt to compensate the memory
      deficits described in aged rats. Hippocampal slices from young, adult and aged
      Wistar rats were pre-incubated, with an NMDA receptor (NMDAR) antagonist,
      memantine (1 MUM, 4 h), and hippocampal LTP was evaluated. The results show that
      memantine significantly decreases the larger LTP magnitude recorded in
      hippocampal slices from aged rats without compromising LTP recorded in slices
      from young and adult animals. To unveil the impact of in vivo administration of
      memantine, different doses (1, 5 and 10 mg/kg/day) or saline vehicle solution
      were intraperitoneally administered, for 15-20 days, to both young and aged
      animals. Memantine did not significantly affect neither the place learning of
      young animals, evaluated by Morris Water Maze, nor LTP recorded from hippocampal
      slices from the same group of animals. However, memantine (5 and 10 mg/kg/day)
      significantly decreased the large LTP recorded in hippocampal slices from aged
      animals. Moreover, aged animals treated with memantine (10 mg/kg/day) showed a
      significantly compromised place learning when compared to aged control animals.
      Overall, these results suggest that the larger LTP observed in aged animals is a
      compensatory phenomenon, rather than pathological. The finding that age-dependent
      blockade of LTP by a NMDAR antagonist leads to learning deficits, implies that
      the increased LTP observed upon aging may be playing an important role in the
      learning process.

PMID- 27889489
TI  - The drug candidate, ADX71441, is a novel, potent and selective positive
      allosteric modulator of the GABAB receptor with a potential for treatment of
      anxiety, pain and spasticity.
AB  - Positive allosteric modulation of the GABAB receptor is a promising alternative
      to direct activation of the receptor as a therapeutic approach for treatment of
      addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, and
      psychosis. Here we describe in vitro and in vivo characterization of a novel,
      potent and selective GABAB positive allosteric modulator (PAM) N-(5-(4-(4-chloro
      3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)-2
      fluorophenyl)acetamide (ADX71441). In vitro, Schild plot and reversibility tests
      at the target confirmed PAM properties of the compound. In mice and rats ADX71441
      is bioavailable after oral administration and is brain penetrant. A single dose
      of ADX71441 had an anxiolytic-like profile in the mouse marble burying test
      (minimum effective dose; MED 3 mg/kg) as well as in the elevated plus maze test
      in mice and rats (both MED 3 mg/kg). Also, in mice, acute administration of
      ADX71441 reduced visceral pain-associated behaviors in the acetic acid-induced
      writhing test. ADX71441 dose-dependently reduced time on rotarod in rats (MED 10
      mg/kg) indicative of muscle-relaxant qualities. ADX71441 reduced locomotor
      activity in mice (10 mg/kg) and rats (3 mg/kg) after single dose; however,
      following sub-chronic administration in mice, 30 mg/kg ADX71441 was associated
      with normal locomotor activity. While acute administration of ADX71441 reduced
      body temperature in rats and mice (both MED 10 mg/kg), the effect in the former
      was transient, rapidly returning to normal levels despite high concentrations of
      the compound remaining in plasma. Thus, the GABAB PAM ADX71441 represents a valid
      therapeutic approach for development of novel treatment of anxiety, pain and
      spasticity.

PMID- 27889490
TI  - Inhibition of cathepsin X reduces the strength of microglial-mediated
      neuroinflammation.
AB  - Inflammation plays a central role in the processes associated with
      neurodegeneration. The inflammatory response is mediated by activated microglia
      that release inflammatory mediators to the neuronal environment. Microglia
      derived lysosomal cathepsins, including cathepsin X, are increasingly recognized
      as important mediators of the inflammation involved in lipopolysaccharide (LPS)
      induced neuroinflammation. The current study was undertaken to investigate the
      role of cathepsin X and its molecular target, gamma-enolase, in neuroinflammation
      and to elucidate the underlying mechanism. We determined that the exposure of
      activated BV2 and EOC 13.31 cells to LPS led to increased levels of cathepsin X
      protein and activity in the culture supernatants in a concentration- and time
      dependent manner. In contrast, LPS stimulation of these two cells reduced the
      release of active gamma-enolase in a manner regulated by the cathepsin X
      activity. Cathepsin X inhibitor AMS36 significantly reduced LPS-induced
      production of nitric oxide, reactive oxygen species and the pro-inflammatory
      cytokines interleukin-6 and tumor necrosis factor-alpha from BV2 cells.
      Inhibition of cathepsin X suppressed microglial activation through the reduced
      caspase-3 activity, together with diminished microglial cell death and apoptosis,
      and also through inhibition of the activity of the mitogen-activated protein
      kinases. Further, SH-SY5Y treatment with culture supernatants of activated
      microglial cells showed that cathepsin X inhibition reduces microglia-mediated
      neurotoxicity. These results indicate that up-regulated expression and increased
      release and activity of microglial cathepsin X leads to microglia activation
      mediated neurodegeneration. Cathepsin X inhibitor caused neuroprotection via its
      inhibition of the activation of microglia. Cathepsin X could thus be a potential
      therapeutic target for neuroinflammatory disorders.

PMID- 27889491
TI  - Pramipexole enhances disadvantageous decision-making: Lack of relation to changes
      in phasic dopamine release.
AB  - Pramipexole (PPX) is a high-affinity D2-like dopamine receptor agonist, used in
      the treatment of Parkinson's disease (PD) and restless leg syndrome. Recent
      evidence indicates that PPX increases the risk of problem gambling and impulse
      control disorders in vulnerable patients. Although the molecular bases of these
      complications remain unclear, several authors have theorized that PPX may
      increase risk propensity by activating presynaptic dopamine receptors in the
      mesolimbic system, resulting in the reduction of dopamine release in the nucleus
      accumbens (NAcc). To test this possibility, we subjected rats to a probability
      discounting task specifically designed to capture the response to disadvantageous
      options. PPX enhanced disadvantageous decision-making at a dose (0.3 mg/kg/day,
      SC) that reduced phasic dopamine release in the NAcc. To test whether these
      modifications in dopamine efflux were responsible for the observed neuroeconomic
      deficits, PPX was administered in combination with the monoamine-depleting agent
      reserpine (RES), at a low dose (1 mg/kg/day, SC) that did not affect baseline
      locomotor and operant responses. Contrary to our predictions, RES surprisingly
      exacerbated the effects of PPX on disadvantageous decision-making, even though it
      failed to augment PPX-induced decreases in phasic dopamine release. These results
      collectively suggest that PPX impairs the discounting of probabilistic losses and
      that the enhancement in risk-taking behaviors secondary to this drug may be
      dissociated from dynamic changes in mesolimbic dopamine release.

PMID- 27889492
TI  - Surgical Complications Following Early Genitourinary Reconstructive Surgery for
      Congenital Adrenal Hyperplasia-Interim Analysis at 6 Years.
AB  - OBJECTIVE: To review the intermediate- to long-term surgical complications
      following feminizing reconstructive surgery for patients with congenital adrenal
      hyperplasia (CAH) at a single tertiary center. Genitourinary reconstructive
      surgery is pivotal to favorable cosmetic and functional outcomes for patients
      with CAH. MATERIALS AND METHODS: We conducted a retrospective review identifying
      26 patients from April 2003 to April 2015 who underwent genitourinary
      reconstructive surgeries. Demographic data and surgical postoperative
      complications (per Unplanned Postoperative Morbidity in Children [UPMC] and
      Clavien-Dindo classification) were evaluated. RESULTS: The average age at the
      time primary surgery was done at our institute was 17 +/- 20 (5-87) months; the
      average length of follow-up was 72.56 +/- 36.95 (4.5-142) months. The average
      length of the common urogenital sinus was 4.5 +/- 1.9 (2.5-6.4) cm, and 15 out of
      22 (68%) patients had high confluence. A total of 7 complications were observed
      in 7 (27%) patients, 3 patients had Clavien grade I and UPMC 0 (dysuria, stitch
      dehiscence, wound separation), and 2 had Clavien grade II and UPMC 1 (urinary
      tract infection). Two (7.6%) patients required revision surgery, and both of them
      had Clavien grade IIIB. One patient had UPMC score 5 (suprapubic tube insertion
      for urinary retention secondary to cicatrization of the surgical site).
      CONCLUSION: Genitourinary reconstructive surgery for CAH patients is well
      tolerated and is successful in toddlers, with low (7.6%) complication rate.
      Revision surgery has successful outcome both functionally and cosmetically. In
      toilet-trained girls, urinary continence can be achieved in all patients
      following feminizing genitoplasty.

PMID- 27889494
TI  - Maternal history of eating disorders: Diet quality during pregnancy and infant
      feeding.
AB  - We studied associations of maternal history of eating disorders (EDs) with diet
      quality of pregnant women and their infants, and breastfeeding practices. We
      included 6196 mother-child pairs from Generation R, a population-based cohort in
      the Netherlands. Maternal history of lifetime EDs was assessed during pregnancy
      with a questionnaire. Dietary intake during pregnancy and in infancy was assessed
      with food-frequency questionnaires and diet quality scores were calculated,
      reflecting adherence to dietary guidelines. Breastfeeding practices were assessed
      with questionnaires at 2, 6, and 12 months. We observed that, after adjustment
      for socioeconomic and lifestyle factors, women with a history of EDs had a higher
      diet quality than women without a history of EDs (B = 0.24 SD, 95%CI: 0.15;
      0.33). Mothers with a history of EDs were less likely to breastfeed (unadjusted
      OR = 0.68, 95%CI: 0.51; 0.93), although no longer statistically significant after
      adjustment (OR = 0.75, 95%CI: 0.55; 1.03). These findings suggest that mothers
      with a history of EDs seem slightly less likely to initiate breastfeeding,
      however, this warrants further investigation. At the age of 1 year, infants of
      mothers with a history of EDs had a higher diet quality (B = 0.15 SD, 95%CI:
      0.02; 0.27). We conclude that mothers with a history of EDs and their infants
      have a relative good diet quality, although follow-up studies are needed to
      assess long-term associations with diet in later childhood and adolescence.

PMID- 27889493
TI  - Partial vs Radical Nephrectomy for T1-T2 Renal Masses in the Elderly: Comparison
      of Complications, Renal Function, and Oncologic Outcomes.
AB  - OBJECTIVE: To compare outcomes of partial nephrectomy (PN) and radical
      nephrectomy (RN) in patients 65 years and older. MATERIALS AND METHODS: Our
      institutional renal mass registry was queried for patients 65 and older with
      solitary cT1-T2 renal mass resected by PN or RN. Clinicopathologic features and
      perioperative outcomes were compared between groups. Renal function outcomes
      measured by change in estimated glomerular filtration rate (eGFR) and freedom
      from eGFR< 45 mL/min/1.73 m2 were analyzed. Multivariate Cox proportional hazard
      models for overall survival and cancer-specific survival were analyzed. RESULTS:
      Overall, 787 patients met inclusion criteria. Of these, 437 (55.5%) underwent PN
      and 350 (44.5%) underwent RN. Median follow-up was 36 months. Patients in the PN
      cohort were younger (median age 70.3 years vs 71.9 years, P < .001), had lower
      American Society of Anesthesiologists scores (2.6 vs 2.8, P = .001), smaller
      tumors (tumor diameter 2.8 cm vs 5.0 cm, P < .001), and lower proportion of renal
      cell carcinoma (76.7% vs 87.4%, P < .001). Perioperative outcomes were similar
      between PN and RN groups as were complications (37.8% vs 38.9%). Estimated change
      in eGFR was less in PN vs RN (6.4 vs 19.7, P < .001) at last follow-up. Overall
      survival and cancer-specific survival were equivalent between modalities.
      CONCLUSION: Because the renal functional benefit of PN is realized over many
      years and the procedure has a higher historical complication rate than RN, some
      suspected elderly patients might benefit more from RN over PN. However, these
      data suggest that elderly patients are not harmed and may potentially benefit
      from PN. Age alone should not be a contraindication to nephron-sparing surgery.

PMID- 27889495
TI  - Health status, physical activity, and orthorexia nervosa: A comparison between
      exercise science students and business students.
AB  - Orthorexia nervosa is described as an exaggerated fixation on healthy food. It is
      unclear whether students in health-oriented academic programs, highly focused on
      physical exercise, are more prone to develop orthorexia nervosa than students in
      other educational areas. The aim was to compare health status, physical activity,
      and frequency of orthorexia nervosa between university students enrolled in an
      exercise science program (n = 118) or a business program (n = 89). The students
      completed the Short Form-36 Health Survey (SF-36), the International Physical
      Activity Questionnaire (IPAQ), and ORTO-15, which defines orthorexia nervosa as a
      sensitive and obsessive behavior towards healthy nutrition. The SF-36 showed that
      exercise science students scored worse than business students regarding bodily
      pain (72.8 vs. 82.5; p = 0.001), but better regarding general health (83.1 vs.
      77.1; p = 0.006). Of 188 students, 144 (76.6%) had an ORTO-15 score indicating
      orthorexia nervosa, with a higher proportion in exercise science students than in
      business students (84.5% vs. 65.4%; p = 0.002). Orthorexia nervosa in combination
      with a high level of physical activity was most often seen in men in exercise
      science studies and less often in women in business studies (45.1% vs. 8.3%; p <
      0.000). A high degree of self-reporting of pain and orthorexia nervosa in
      exercise science students may cause problems in the future, since they are
      expected to coach others in healthy living. Our findings may be valuable in the
      development of health-oriented academic programs and within student healthcare
      services.

PMID- 27889496
TI  - How parents describe picky eating and its impact on family meals: A qualitative
      analysis.
AB  - Children are frequently described as being picky eaters. However, this term has
      been inconsistently defined in prior research. There is limited qualitative
      research investigating how parent's define picky eating, how they respond to it,
      or how they see picky eating impacting their child's dietary intake or the family
      meal. For this study, parents (n = 88) of siblings (ages 2-18 years old) were
      interviewed in their homes. The semi-structured interviews focused on parent
      feeding practices and child eating behaviors. A qualitative content analysis
      approach was used to analyze the data; themes regarding picky eating emerged.
      Results of this study show that the majority of parents (94% female; mean age 35
      years) were from minority and low income homes. The following themes regarding
      picky eating were identified: 1) children were frequently described as being
      picky eaters; 2) parents defined picky eating in a variety of ways (i.e., not
      liking a few foods; limited intake; resisting texture or appearance of foods;
      resistance to new foods); 3) picky eating impacted the family meal (i.e.,
      promotes meal-related parent stress; impacts meal preparation); and 4) parents
      responded to picky eating in a variety of ways (i.e., require child tries food;
      allow child to make separate meal; allow child not to eat; parent makes a
      separate meal; allows child to choose only food he/she likes; requires child to
      eat anyway). This study demonstrates that many parents experience child picky
      eating and report that it impacts family meals. Additionally, study results
      provide information on the specific ways pickiness impacts the family meal and
      how parents respond to pickiness. This study also provides guidance for future
      studies wishing to define picky eating or evaluate the prevalence of child
      pickiness.

PMID- 27889497
TI  - In vivo effect of borneol on rat hepatic CYP2B expression and activity.
AB  - CYP2B subfamily accounts for 2-10% of total hepatic CYP450 enzymes and
      participate in the metabolism of around 8% of clinical drugs. Borneol has been
      widely used in traditional Chinese medicine for thousands of years. There are
      many studies about borneol-induced promoting penetration role for a number of
      drugs through various physiologic barriers, whereas there is no report involved
      the effect of borneol on hepatic CYP2B. The present work studied the in vivo
      effect of borneol on the expression and activity of rat hepatic CYP2B. The
      results indicated that the oral administration of borneol (33, 100 and 300
      mg/kg/d) to rats for consecutive 7 days increased the hepatic CYP2B1/2 activity
      by 1.4-, 1.7- and 2.8-fold, hepatic CYP2B1 mRNA expression by 6.3-, 8.7- and 18.1
      fold, and hepatic CYP2B1/2 protein expression by 1.2-, 1.9- and 2.6-fold,
      respectively compared to the control. Additionally, in the borneol pre-dosing
      (300 mg/kg/d for consecutive 7 days) rats, the increased Clint and decreased AUC0
      24 of bupropion were observed as compared to the control. Moreover, there were no
      obvious effects on CAR protein level in rat liver microsome and nucleus following
      the borneol treatment. Taken together, our observations indicate that borneol is
      an in vivo inducer of rat hepatic CYP2B with different regulatory mechanism from
      phenobarbital-like inducers which caused CYP2B induction with CAR activation.

PMID- 27889499
TI  - The OsAMT1.1 gene functions in ammonium uptake and ammonium-potassium homeostasis
      over low and high ammonium concentration ranges.
AB  - Rice (Oryza sativa) grown in paddy fields is an ammonium (NH4+)-preferring crop;
      however, its AMT-type NH4+ transporters that mediate root N acquisition have not
      been well characterized yet. In this study, we analyzed the expression pattern
      and physiological function of the OsAMT1.1 gene of the AMT1 subfamily in rice.
      OsAMT1.1 is located in the plasma membrane and is mainly expressed in the root
      epidermis, stele and mesophyll cells. Disruption of the OsAMT1.1 gene decreased
      the uptake of NH4+, and the growth of roots and shoots under both low NH4+ and
      high NH4+ conditions. OsAMT1.1 contributed to the short-term (5 min) 15NH4+
      influx rate by approximately one-quarter, irrespective of the NH4+ concentration.
      Knockout of OsAMT1.1 significantly decreased the total N transport from roots to
      shoots under low NH4+ conditions. Moreover, compared with the wild type, the
      osamt1.1 mutant showed an increase in the potassium (K) absorption rate under
      high NH4+ conditions and a decrease under low NH4+ conditions. The mutants
      contained a significantly high concentration of K in both the roots and shoots at
      a limited K (0.1 mmol/L) supply when NH4+ was replete. Taken together, the
      results indicated that OsAMT1.1 significantly contributes to the NH4+ uptake
      under both low and high NH4+ conditions and plays an important role in N-K
      homeostasis in rice.

PMID- 27889498
TI  - BLOC-2 subunit HPS6 deficiency affects the tubulation and secretion of von
      Willebrand factor from mouse endothelial cells.
AB  - Hermansky-Pudlak syndrome (HPS) is a recessive disorder with bleeding diathesis,
      which has been linked to platelet granule defects. Both platelet granules and
      endothelial Weibel-Palade bodies (WPBs) are members of lysosome-related
      organelles (LROs) whose formation is regulated by HPS protein associated
      complexes such as BLOC (biogenesis of lysosome-related organelles complex) -1, 
      2, -3, AP-3 (adaptor protein complex-3) and HOPS (homotypic fusion and protein
      sorting complex). Von Willebrand factor (VWF) is critical to hemostasis, which is
      stored in a highly-multimerized form as tubules in the WPBs. In this study, we
      found the defective, but varying, release of VWF into plasma after desmopressin
      (DDAVP) stimulation in HPS1 (BLOC-3 subunit), HPS6 (BLOC-2 subunit), and HPS9
      (BLOC-1 subunit) deficient mice. In particular, VWF tubulation, a critical step
      in VWF maturation, was impaired in HPS6 deficient WPBs. This likely reflects a
      defective endothelium, contributing to the bleeding tendency in HPS mice or
      patients. The differentially defective regulated release of VWF in these HPS
      mouse models suggests the need for precise HPS genotyping before DDAVP
      administration to HPS patients.

PMID- 27889500
TI  - Enhancing phosphorus uptake efficiency through QTL-based selection for root
      system architecture in maize.
AB  - Root system architecture (RSA) plays an important role in phosphorus (P)
      acquisition, but enhancing P use efficiency (PUE) in maize via genetic
      manipulation of RSA has not yet been reported. Here, using a maize recombinant
      inbred line (RIL) population, we investigated the genetic relationships between
      PUE and RSA, and developed P-efficient lines by selection of quantitative trait
      loci (QTLs) that coincide for both traits. In low-P (LP) fields, P uptake
      efficiency (PupE) was more closely correlated with PUE (r = 0.48-0.54), and RSA
      in hydroponics was significantly related to PupE (r = 0.25-0.30) but not to P
      utilization efficiency (PutE). QTL analysis detected a chromosome region where
      two QTLs for PUE, three for PupE and three for RSA were assigned into two QTL
      clusters, Cl-bin3.04a and Cl-bin3.04b. These QTLs had favorable effects from
      alleles derived from the large-rooted and high-PupE parent. Marker-assisted
      selection (MAS) identified nine advanced backcross-derived lines carrying Cl
      bin3.04a or Cl-bin3.04b that displayed mean increases of 22%-26% in PUE in LP
      fields. Furthermore, a line L224 pyramiding Cl-bin3.04a and Cl-bin3.04b showed
      enhanced PupE, relying mainly on changes in root morphology, rather than root
      physiology, under both hydroponic and field conditions. These results highlight
      the physiological and genetic contributions of RSA to maize PupE, and provide a
      successful study case of developing P-efficient crops through QTL-based
      selection.

PMID- 27889501
TI  - Endophthalmitis After Clear Corneal Cataract Surgery: Outcomes Over Two Decades.
AB  - PURPOSE: To report the clinical features, causative organisms, and visual acuity
      (VA) outcomes associated with acute-onset endophthalmitis after clear corneal
      cataract surgery over the past 2 decades. DESIGN: Retrospective case series.
      METHODS: Clinical and microbiology records were reviewed for 63 eyes of 63
      patients who presented to a tertiary referral center between 2006 and 2015 with
      culture-positive endophthalmitis occurring within 6 weeks of clear corneal
      cataract surgery. RESULTS: The mean time between surgery and diagnosis of
      endophthalmitis was 8 days (median 6 days). The initial treatment included
      intravitreal vancomycin and ceftazidime in 59 of 63 (94%) eyes and intravitreal
      vancomycin and amikacin in 4 of 63 (6%) eyes. Intravitreal dexamethasone was used
      in 50 of 63 (79%) eyes. A vitreous tap and injection with antibiotics was
      performed as the initial treatment in 57 of 63 (90%) eyes and pars plana
      vitrectomy in 6 of 63 (10%) eyes. Coagulase-negative Staphylococcus was isolated
      in 39 of 63 (62%) eyes, Staphylococcus aureus in 7 of 63 (11%) eyes, and
      Streptococcus species in 7 of 63 (11%) eyes. A VA of >=20/40 was achieved in 24
      of 63 (38%) eyes. None of the gram-positive isolates were vancomycin resistant.
      Twenty-four of 49 isolates (49%) were sensitive to cephalothin, cefazolin, and
      cefuroxime. Sensitivity to fluoroquinolones included 22 of 52 (42%) to
      levofloxacin, 20 of 54 (37%) to ciprofloxacin, 16 of 47 (34%) to moxifloxacin,
      and 3 of 13 (23%) to gatifloxacin. CONCLUSION: Causative organisms and visual
      outcomes are similar to those reported in the prior decade. In the current study,
      a number of isolates were resistant to cephalosporins and fluoroquinolones.

PMID- 27889502
TI  - Role of Lamellar Hole-Associated Epiretinal Proliferation in Lamellar Macular
      Holes.
AB  - PURPOSE: To compare the morphologic and functional characteristics and response
      to surgery of lamellar macular holes (LMHs) with and without lamellar hole
      associated epiretinal proliferation (LHEP) and standard epiretinal membrane
      (ERM). DESIGN: Retrospective observational case series. METHODS: Setting:
      Vitreoretinal clinical practice. STUDY POPULATION: Eigthy-four eyes of 84
      patients. The included eyes must present an irregular foveal contour and schitic
      or cavitated lamellar separation of neurosensory retina on spectral-domain
      optical coherence tomography (SDOCT) and an area of increased autofluorescence on
      blue fundus autofluorescence (B-FAF). Twenty-six eyes underwent pars plana
      vitrectomy (PPV). MAIN OUTCOME MEASURES: Logarithm of minimum angle of resolution
      (logMAR) best-corrected visual acuity (BCVA) and evolution of morphologic
      characteristics. RESULTS: Standard ERM alone, LHEP alone, and concomitant ERM and
      LHEP were found in 51.2%, 13.1%, and 35.7% of the cases, respectively. A
      substantial stability of functional and morphologic parameters throughout the
      follow-up period was observed in the eyes that did not undergo surgery
      indipendently from the associated epiretinal material. The most significant
      change, observed in the preoperative period, in the eyes that underwent surgery,
      was the thinning of the central foveal thickness (CFT, P < .001). In the operated
      eyes, logMAR BCVA continuosly improved during the postoperative period (P =
      .006), CFT was found increased, and diameters of the hole were found reduced
      since the first month after operation (P < .001). CONCLUSIONS: In eyes with LMHs,
      presence of LHEP without any trace of standard ERM is rare. The presence of LHEP
      does not seem to influence the natural course of the disease and the response to
      surgery.

PMID- 27889503
TI  - Gamma Knife Radiosurgery for Uveal Metastases: Report of Three Cases and a Review
      of the Literature.
AB  - PURPOSE: Uveal metastases are ophthalmologic tumors that have historically been
      treated by fractionated external beam radiation therapy or invasive
      brachytherapy. The need for rapid response and less invasive management options
      led the authors to explore the use of Gamma Knife stereotactic radiosurgery (SRS)
      for this common problem. DESIGN: Interventional case series. METHODS: To prevent
      eye movement during the procedure, all 3 patients underwent a retrobulbar
      anesthetic block followed by magnetic resonance imaging to detect the target. All
      tumors were treated in a single procedure using the 4C or Perfexion Gamma Knife.
      The tumors received a minimal tumor dose of 14-20 Gy. Two patients also underwent
      SRS for additional intracranial metastases. RESULTS: At follow-up, performed
      between 4 and 15 months after SRS, all 3 patients demonstrated a reduction in
      uveal tumor volumes. One patient developed decreased visual acuity secondary to
      radiation retinopathy. CONCLUSION: In this early experience, SRS was found to be
      an effective management option for uveal metastases associated with systemic
      cancer. Patients can be screened and treated effectively early after diagnosis
      using a joint approach between ophthalmologists and neurosurgeons. Systemic
      oncologic care can continue without interruption.

PMID- 27889504
TI  - Responses of the sea anemone, Exaiptasia pallida, to ocean acidification
      conditions and zinc or nickel exposure.
AB  - Ocean acidification, caused by increasing atmospheric carbon dioxide (CO2), is a
      growing concern in marine environments. Land-based sources of pollution, such as
      metals, have also been a noted problem; however, little research has addressed
      the combined exposure of both pollutants to coral reef organisms. In this study
      we examined tissue metal accumulation and physiological effects (activity of anti
      oxidant enzymes, catalase and glutathione reductase) in the sea anemone,
      Exaiptasia pallida after exposure to increased CO2, as well as zinc (Zn) or
      nickel (Ni). After exposure to four concentrations (nominal values=control, 10,
      50, 100MUg/L) of Zn or Ni over 7days, both metals accumulated in the tissues of
      E. pallida in a concentration-dependent manner. Anemones exposed to elevated CO2
      (1000ppm) accumulated significant tissue burdens of Zn or Ni faster (by 48h) than
      those exposed to the same metal concentrations at ambient CO2. No differences
      were observed in catalase activity due to Zn exposure; however, 50MUg/L Ni caused
      a significant increase in catalase activity at ambient CO2. No significant effect
      on catalase activity from CO2 exposure alone was observed. Glutathione reductase
      activity was affected by increased Zn or Ni exposure and those effects were
      influenced by increased CO2. Results of this study provide insight into the toxic
      mechanisms and environmental implications of CO2 and Zn or Ni exposure to the
      cnidarian E. pallida.

PMID- 27889505
TI  - Candesartan ameliorates arsenic-induced hypertensive vascular remodeling by
      regularizing angiotensin II and TGF-beta signaling in rats.
AB  - Arsenic exposure can cause several cardiovascular diseases, including
      hypertension, atherosclerosis and microvascular disease. Earlier, we reported
      that arsenic-mediated enhancement of angiotensin II (AngII) signaling can impair
      vascular physiology. Here, we investigated whether the AT1 receptor (AT1R)
      blocker candesartan can ameliorate the arsenic-induced hypertensive vascular
      remodeling in rats and whether the amelioration could relate to attenuation in
      vascular AngII and TGF-beta signaling. Rats were exposed to sodium arsenite
      (50ppm) through drinking water for 90 consecutive days. Candesartan (1mg/kg bw,
      orally) was administered once daily during the last 30days of arsenic exposure.
      Non-invasive blood pressure was recorded weekly in conscious rats, while AngII
      induced change in mean arterial pressure in anaesthetized rats was measured by
      invasive method on the 91st day. On this day, blood was collected from other
      animals for measuring AngII level. Western blot of AT1, AT2 and TbetaRII
      receptors; ELISA of PTK, RasGAP, ERK-1/2, TGF-beta and CTGF; immunohistochemistry
      of phosphorylated Smad3, Smad4 and collagen III, hydroxyproline/total collagen
      estimation, collagen deposition by Masson's trichrome staining and
      histomorphometry were carried out in thoracic aorta. Arsenic increased non
      invasive systolic, diastolic and mean arterial pressure. Further, AngII caused
      concentration-dependent incremental change in mean arterial pressure in the
      arsenic-exposed rats. Arsenic upregulated AT1 and TbetaRII receptor proteins;
      elevated the levels of PTK, ERK-1/2, TGF-beta and CTGF, decreased RasGAP level
      and augmented the immunoreactivities of Smad3, Smad4 and collagen III. Arsenic
      also increased hydroxyproline/total collagen level, proliferation of collagen
      fibres and thickness of aortic wall and collagenous adventitia. Candesartan
      normalized blood pressure, regularized receptor expressions, MAP kinase and TGF
      beta signaling, restored collagen deposition and regressed aortic thickness. Our
      results demonstrate that candesartan can ameliorate the arsenic-mediated systemic
      hypertension and vascular remodeling in rats by regularizing the signaling
      pathways of AngII and TGF-beta.

PMID- 27889506
TI  - Genetic and transcriptional study of glutathione metabolism in Oenococcus oeni.
AB  - Although Oenococcus oeni is the main species that is responsible for malolactic
      fermentation (MLF), harsh wine conditions can limit its performance. Although
      several mechanisms underlying the response to stress have been studied in this
      species, little is known regarding the cellular systems that protect against
      oxidative stress in other bacteria, such as glutathione (GSH). O. oeni cannot
      synthesize GSH but contains several genes related to its utilization. In this
      study, the relative expression (RE) of the seven genes involved in the GSH redox
      system found in O. oeni PSU-1 (gshR, gpo, three glutaredoxin-like genes and two
      subunits of an hypothetical transporter) has been measured. The study was
      performed using three strains, with each exhibiting a different GSH uptake
      capacity. The strains were grown in a stress-adaptation medium supplemented with
      5mM GSH and under different adaptation stress conditions (pH4 and 6% ethanol).
      The RE showed that only some of these genes, including one for a possible
      glutaredoxin (OEOE_RS04215) and cydC for a subunit of a putative GSH transporter
      (OEOE_RS1995), responded to the addition of GSH. The presence of ethanol had a
      relevant effect on gene expression. Among the studied genes, the one for a NrdH
      redoxin (OEOE_RS00645) showed a common response to ethanol in the strains, being
      over-expressed when grown with GSH. In most cases, the transcriptional changes
      were more evident for the strain with a higher capacity of GSH uptake. Malolactic
      performance of the three strains after pre-adaptation was evaluated in wine-like
      media (12% ethanol and pH3.4). It was observed that the addition of GSH during
      pre-adaptation growth had a protective role in the cells exposed to low pH and
      ethanol, resulting in a quicker MLF.

PMID- 27889507
TI  - CYP2C9 Genotypes Modify Benzodiazepine-Related Fall Risk: Original Results From
      Three Studies With Meta-Analysis.
AB  - OBJECTIVE: To investigate whether the CYP2C9*2 and *3 variants modify
      benzodiazepine-related fall risk. DESIGN: Three prospective studies; the
      Rotterdam Study, B-PROOF, and LASA. SETTING: Community-dwelling individuals
      living in or near five Dutch cities. PARTICIPANTS: There were 11,485 participants
      aged >=55 years. MEASUREMENTS: Fall incidents were recorded prospectively.
      Benzodiazepine use was determined using pharmacy dispensing records or
      interviews. Cox proportional hazard models adjusted for age and sex were applied
      to determine the association between benzodiazepine use and fall risk stratified
      for CYP2C9 genotype and comparing benzodiazepine users to nonusers. The results
      of the three studies were combined applying meta-analysis. Within benzodiazepine
      users, the association between genotypes and fall risk was also assessed.
      RESULTS: Three thousand seven hundred five participants (32%) encountered a fall
      during 91,996 follow-up years, and 4% to 15% (depending on the study population)
      used benzodiazepines. CYP2C9 variants had frequencies of 13% for the *2 allele
      and 6% for the *3 allele. Compared to nonusers, current benzodiazepine use was
      associated with an 18% to 36% increased fall risk across studies with a combined
      hazard ratio (HR) = 1.26 (95% confidence interval [CI], 1.13; 1.40). CYP2C9*2 or
      *3 allele variants modified benzodiazepine-related fall risk. Compared to
      nonusers, those carrying a CYP2C9*2 or *3 allele and using benzodiazepines had a
      45% increased fall risk (HR, 1.45 95% CI, 1.21; 1.73), whereas CYP2C9*1
      homozygotes using benzodiazepines had no increased fall risk (HR, 1.14; 95% CI,
      0.90; 1.45). Within benzodiazepine users, having a CYP2C9*2 or *3 allele was
      associated with an increased fall risk (HR, 1.35; 95% CI, 1.06; 1.72).
      Additionally, we observed an allele dose effect; heterozygous allele carriers had
      a fall risk of (HR = 1.30; 95% CI, 1.05; 1.61), and homozygous allele carriers of
      (HR = 1.91 95% CI, 1.23; 2.96). CONCLUSIONS: CYP2C9*2 and *3 allele variants
      modify benzodiazepine-related fall risk. Those using benzodiazepines and having
      reduced CYP2C9 enzyme activity based on their genotype are at increased fall
      risk. In clinical practice, genotyping might be considered for elderly patients
      with an indication for benzodiazepine use. However, because the exact role of
      CYP2C9 in benzodiazepine metabolism is still unclear, additional research is
      warranted.

PMID- 27889508
TI  - Physiological responses and changes in gene expression in the large yellow
      croaker Larimichthys crocea following exposure to hypoxia.
AB  - Organisms at all levels of evolutionary complexity react to hypoxic stress. To
      clarify the effects of acute hypoxia on physiological and biochemical responses
      of Larimichthys crocea, we measured the activity levels of the antioxidant
      enzymes superoxide dismutase and catalase, hemoglobin concentration, functional
      indices of the liver (aspartate transaminase, alanine transaminase), heart
      (phosphocreatine kinase), and immune system (alkaline phosphatase), as well as
      mRNA expression levels of the immunity-related genes Hsp70 and HIF-1alpha at
      different time points of hypoxic. In addition, liver, gill, and kidney samples
      were histologically analyzed. We found that hemoglobin concentration and all
      enzyme activities increased during hypoxia, although these effects were transient
      and most indices returned to basal levels thereafter. The extent of the increase
      in the parameter values was inversely proportional to the dissolved oxygen
      content. Hsp70 and HIF-1alpha mRNA expression levels increased significantly in
      the blood, liver, gills, and kidneys following exposure to hypoxia, which may
      play an important role in protecting fish against oxidative damage. However, we
      found histological evidence of hypoxia-induced injuries to the gills, liver, and
      kidneys, which are involved in breathing, detoxification, and osmotic balance
      maintenance, respectively. Thus, despite the upregulation of defensive
      mechanisms, acute hypoxia still caused irreversible damage of organs. In
      conclusion, we observed that, in response to acute hypoxic stress, L. crocea
      enhances immune defensive function and antioxidant capacity. A better
      understanding of the regulation of the molecular anti-hypoxia mechanisms can help
      speeding up the selective breeding of hypoxia-tolerant L. crocea.

PMID- 27889509
TI  - Ultrastructural and developmental evidence of phytotoxicity on cos lettuce
      (Lactuca sativa) associated with nonylphenol exposure.
AB  - It has long been understood that the presence of endocrine disrupter chemicals
      (EDCs) in water can affect the reproductive, behavioural and regulatory systems
      of different types of mammals. Thus far, only a handful of studies have examined
      its impact on plant systems. Present research is limited to the potential uptake
      of these chemicals by plants and the general phytotoxic effects it can elicit.
      The aim of this study was to determine what effect an EDC has on developing plant
      and cell organelles and how it affects it. In this study, cos lettuce plants were
      exposed to different concentrations of nonylphenol (NP), an EDC, in a static
      hydroponic system. Changes in plant morphology, mass and length, chlorophyll
      content, as well as electrolyte leakage were examined. Furthermore an in-depth
      investigation of the plant cell ultrastructure was carried out with transmission
      electron microscopy. Results indicated that cos lettuce growth was severely
      restricted, chlorophyll content was reduced, leakage of electrolytes increased
      and roots were stunted especially after >=3200 MUg/l NP exposures. The structure
      of the rough endoplasmic reticulum, vacuole and chloroplast were also changed.
      This study emphasizes the importance of water quality management, since the
      presence of an EDC, like NP, can negatively impact the yield and internal
      structure of one of the world's most significant salad crops, namely lettuce.

PMID- 27889510
TI  - Amine-functionalized, multi-arm star polymers: A novel platform for removing
      glyphosate from aqueous media.
AB  - We describe a novel method for efficiently removing glyphosate from aqueous media
      via adsorption onto highly functionalized star-shaped polymeric particles. These
      particles have a polystyrene core with more than 35 attached methacrylate polymer
      arms, each containing a plurality of pendant amines (poly(dimethylamino ethyl
      methacrylate): PDMAEMA) that are partially protonated in water. Kinetic studies
      demonstrate that these star-polymers successfully remove up to 93% of glyphosate
      present in aqueous solution (feed concentration: 5 ppm), within 10 min contact
      time, outperforming activated carbon, which removed 33% after 20 min. On these
      star-polymers, glyphosate adsorption closely follows the Langmuir model
      indicating monolayer coverage at most. Ionic interaction between the protonated
      amines and glyphosate's dissociated carboxylic and phosphoric acid groups lead to
      effective glyphosate capture even at feed concentrations below 1 ppm. Surface
      charge of these star polymers and dissociation of glyphosate are both influenced
      by pH, thus glyphosate removal efficiency increases from 63% to 93% when pH
      increases from 4.2 to 7.7. NMR studies conducted with butylamine as a proxy for
      these polymeric particles confirm that the amine group binds with both
      glyphosate's carboxylic and phosphoric acid groups when its concentrations are in
      a 2:1 or higher molar ratio with glyphosate.

PMID- 27889511
TI  - Historical sources of polychlorinated biphenyls to the sediment of the New
      York/New Jersey Harbor.
AB  - Using dated sediment cores, polychlorinated biphenyl (PCB) congener
      concentrations in the New York/New Jersey Harbor and Lower Hudson River were
      investigated using Positive Matrix Factorization. Of the seven factors resolved,
      six represent Aroclors in various stages of weathering. Factor 1 resembles
      Aroclor 1242 and is consistent with the Upper Hudson River PCB signal associated
      with the General Electric capacitor plants near Hudson Falls, NY. This factor is
      the dominant source of PCBs in the upper layers of the sediment core collected in
      the Lower Hudson River. Factor 2 (Aroclor 1248) was the dominant PCB component in
      the core depths corresponding with around 1970, but it has decreased more rapidly
      since its peak (estimated half-life of about 5 years) than factor 1 (half-life of
      about 14 years), suggesting that PCBs from the Upper Hudson have delayed the
      recovery of the Harbor from PCB contamination. The seventh factor, comprised of
      PCBs 206, 208, and 209, was greatest in concentration in the deepest core slices
      and is thought be associated with inadvertent production of PCBs during the
      manufacture of titanium dioxide and/or with foundry waxes containing PCBs. PCB
      11, which is thought to be associated with the use of color organic pigments, was
      examined separately and was detected in sediment throughout the Harbor. Its
      maximum concentrations generally occurred at the same depth as the maximum total
      PCB concentrations, suggesting that PCB 11 concentrations decreased after the mid
      1970s.

PMID- 27889512
TI  - Genotoxicity and growth inhibition effects of aniline on wheat.
AB  - Aniline is a synthetic compound widely used in industrial and pesticide
      production, which can lead to environmental pollution. Its high concentration in
      rivers and lakes is hazardous to aquatic species. Although the mechanism of
      aniline toxicity has been studied extensively in animals and algae, little is
      known about its genotoxicity in plants. In this study, we investigated the
      genotoxicity effects of aniline on wheat root tip cells. The mitotic index of
      wheat root tip cells decreased when the aniline test concentration was higher
      than 10 mg L-1. The frequency of micronucleus and chromosomal aberrations
      increased at aniline concentrations ranging between 5 and 100 mg L-1, and reached
      23.30/00 +/- 0.30/00 and 8.90/00 +/- 0.680/00, respectively, at an aniline
      concentration of 100 mg L-1. These values were sevenfold higher than those in the
      control group. The wheat seedlings showed various growth toxicity effects under
      different concentrations of aniline. The shoot height, root length, fresh weight,
      and dry weight of wheat seedlings decreased at aniline test concentrations
      ranging between 25 and 200 mg L-1. At 200 mg L-1 aniline, the dry weight was only
      one-third that of the control group. Overall, the findings of this study provide
      evidence that aniline is a serious environmental pollutant causing deleterious
      genotoxic effects on wheat root tip cells and growth toxic effects on wheat
      seedlings. However, understanding the mechanisms that underlie aniline
      genotoxicity in plants needs further study.

PMID- 27889513
TI  - By-product identification and phytotoxicity of biodegraded Direct Yellow 4 dye.
AB  - Citrus limon peroxidase mediated decolourization of Direct Yellow 4 (DY4) was
      investigated. The process variables (pH, temperature, incubation time, enzyme
      dose, H2O2 amount, dye concentration, co-metal ions and surfactants) were
      optimized for maximum degradation of dye. Maximum dye decolourization of 89.47%
      was achieved at pH 5.0, temperature 50  degrees C, enzyme dose 24 U/mL, H2O2
      concentration 0.25 mM and DY4 concentration 18.75 mg/L and incubation time 10
      min. The co-metal ions and surfactants did not affect the dye decolourization
      significantly. Response surface analysis revealed that predicted values were in
      agreement with experimentally determined responses. The degradation products were
      identified by UPLC/MS analysis and degradation pathway was proposed. Besides,
      phytotoxicity assay revealed a considerable detoxification in response of
      biodegradation of DY4 dye. C. limon showed promising efficiency for DY4
      degradation and could possibly be used for the remediation of textile effluents.

PMID- 27889514
TI  - Cadmium alters the expression of small heat shock protein genes in the aquatic
      midge Chironomus riparius.
AB  - Cadmium (Cd) is a widespread and highly toxic heavy metal of particular
      ecotoxicological relevance for aquatic ecosystems. It occurs naturally in the
      environment but is also an industrial pollutant with extensively researched
      carcinogenic potentials. Heat shock proteins (HSPs) are chaperones that play an
      important role in maintaining protein homeostasis under stress conditions. Small
      heat shock proteins (sHSPs) comprise the most diverse group of the HSPs family.
      They are expressed both constitutively and by stress-induction. The midge
      Chironomus riparius is widely used as a test species in aquatic toxicology. In
      the present study, Reverse Transcription Polymerase Chain Reaction (RT-PCR) was
      used to evaluate the effects of acute Cd exposure to the expression profile of
      seven shsp genes (hsp17, hsp21, hsp22, hsp23, hsp24, hsp27, and hsp34) in C.
      riparius larvae. Results show a specific pattern of response with a rapid
      response by hsp27, which was downregulated at 2-6 h, while the rest of the shsp
      genes remained unaltered except for hsp17 at 2 h, which was upregulated. However,
      at 24 h of exposure are observed high levels of hsp23, hsp24, hsp27, and hsp34
      transcription while hsp22 mRNA levels were downregulated and hsp17 and hsp21
      remained unaltered. These changes in gene expression suggest a functional
      diversity between the sHSPs in the cellular response to heavy metal stress. The
      differential pattern in comparison with heat shock supports a specific profile
      depending on the stress supporting the use of shsp genes as suitable biomarkers
      for ecotoxicological studies on aquatic systems.

PMID- 27889515
TI  - Quality assessment of Traditional Chinese Medicine using HPLC-PAD combined with
      Tchebichef image moments.
AB  - Traditional Chinese medicines have gotten growing attention and the product
      quality also became uneven. In this paper, Tchebichef image moments coupled with
      high performance liquid chromatography with photodiode array detector were
      proposed to the similarity analysis of the fourteen batches of Pudilan Xiaoyan
      tablets (Chinese medicine complex), which were based on the grayscale images of
      three dimensional (3D) fingerprint spectra. Hierarchical cluster analysis was
      used for displaying the classification results. As a comparison, traditional
      principal component analysis (PCA) method based on the chromatograms under single
      fixed wavelength was carried out on the same samples. The analytical results
      indicated that the proposed approach could provide more accurate and reasonable
      results owing to its powerful invariant and multi-resolution capability of image
      moments.

PMID- 27889516
TI  - Lenalidomide enhances the function of dendritic cells generated from patients
      with multiple myeloma.
AB  - Lenalidomide (LEN) has been used as an immunomodulatory drug with direct and
      indirect anti-tumor effects. In this study, we evaluated the effect of LEN on the
      differentiation, maturation, and function of dendritic cells (DCs) in patients
      with multiple myeloma in vitro. Various doses of LEN were added after the
      monocytes had differentiated into immature DCs and were activated into mature
      DCs. LEN (5 MUg/mL) was the optimal concentration to promote differentiation and
      maturation of DCs. Immature DCs treated with LEN exhibited enhanced endocytic
      capacity. Mature DCs treated with LEN produced higher levels of interleukin
      12p70, possessed stronger allogeneic T-cell stimulation capacity, reduced the
      number of suppressor cells, and generated antigen-specific cytotoxic T
      lymphocytes more potently compared with control DCs. These results suggest that
      LEN enhanced the function of DCs generated from patients with multiple myeloma by
      stimulating the capacity of allogeneic T cells, inhibiting the generation of
      immunosuppressive cells, inducing naive T cells toward Th1 polarization, and
      generating potent myeloma-specific cytotoxic T lymphocytes.

PMID- 27889517
TI  - Rice pectin methylesterase inhibitor28 (OsPMEI28) encodes a functional PMEI and
      its overexpression results in a dwarf phenotype through increased pectin
      methylesterification levels.
AB  - Pectin methylesterases (PMEs, EC 3.1.1.11) belonging to carbohydrate esterase
      family 8 cleave the ester bond between a galacturonic acid and an methyl group
      and the resulting change in methylesterification level plays an important role
      during the growth and development of plants. Optimal pectin methylesterification
      status in each cell type is determined by the balance between PME activity and
      post-translational PME inhibition by PME inhibitors (PMEIs). Rice contains 49
      PMEIs and none of them are functionally characterized. Genomic sequence analysis
      led to the identification of rice PMEI28 (OsPMEI28). Recombinant OsPMEI28
      exhibited inhibitory activity against commercial PME protein with the highest
      activities detected at pH 8.5. Overexpression of OsPMEI28 in rice resulted in an
      increased level of cell wall bound methylester groups and differential changes in
      the composition of cell wall neutral monosaccharides and lignin content in culm
      tissues. Consequently, transgenic plants overexpressing OsPMEI28 exhibited dwarf
      phenotypes and reduced culm diameter. Our data indicate that OsPMEI28 functions
      as a critical structural modulator by regulating the degree of pectin
      methylesterification and that an impaired status of pectin methylesterification
      affects physiochemical properties of the cell wall components and causes abnormal
      cell extensibility in rice culm tissues.

PMID- 27889518
TI  - Proteomic analysis provides insights into changes in the central metabolism of
      the cambium during dormancy release in poplar.
AB  - Seasonal cycling of growth and dormancy is an important feature for the woody
      plants growing in temperate zone, and dormancy is an effective strategy for
      surviving the winter stress. But the mechanisms of dormancy maintenance and its
      release are still not clear, especially little information is available with
      regard to the changes of proteome during the process. A better understanding in
      the function of proteins and their related metabolic pathways would expand our
      knowledge of the mechanisms of dormancy maintenance and its release in trees. In
      this study, we employed the isobaric tags for relative and absolute
      quantification (iTRAQ) approach with LC-MS/MS analysis to investigate the protein
      profile changes during dormancy release in poplar. In addition, the change of
      lipid, total insoluble carbohydrates and starch granules in the cambium was
      investigated by histochemical methods. A total of 3789 proteins were identified
      in poplar cambial tissues, 1996 of them were significantly altered during the
      dormancy release. Most of the altered proteins involved in signaling,
      phytohormone, energy metabolism, stress and secondary metabolism by functional
      analysis. Our data shows that the lipid metabolism proteins changed significantly
      both in the release stage of eco- and endodormancy, while the changes of
      carbohydrate metabolism proteins were mainly in endo-dormancy release stage.
      Moreover, histochemical results were consistent with the proteomic data. Our
      results reveal diverse stage-specific metabolism changes during the dormancy
      release process induced by chilling in poplar, which provided new information
      regarding the regulation mechanisms of dormancy maintenance and its release in
      trees.

PMID- 27889519
TI  - Iron-induced nitric oxide leads to an increase in the expression of ferritin
      during the senescence of Lotus japonicus nodules.
AB  - Iron is an essential nutrient for legume-rhizobium symbiosis and accumulates
      abundantly in the nodules. However, the concentration of free iron in the cells
      is strictly controlled to avoid toxicity. It is known that ferritin accumulates
      in the cells as an iron storage protein. During nodule senescence, the expression
      of the ferritin gene, Ljfer1, was induced in Lotus japonicus. We investigated a
      signal transduction pathway leading to the increase of Ljfer1 in the nodule. The
      Ljfer1 promoter of L. japonicus contains a conserved Iron-Dependent Regulatory
      Sequence (IDRS). The expression of Ljfer1 was induced by the application of iron
      or sodium nitroprusside, which is a nitric oxide (NO) donor. The application of
      iron to the nodule increased the level of NO. These data strongly suggest that
      iron-induced NO leads to increased expression of Ljfer1 during the senescence of
      L. japonicus nodules.

PMID- 27889520
TI  - Profiling of volatile organic compounds released from individual intact juvenile
      and mature citrus leaves.
AB  - Plants release volatiles to communicate with each other and to attract or repel
      insects. The methods used to collect volatiles are varied. Here, we describe a
      simple solvent-less, solid phase microextraction-based method to collect the
      volatiles released from intact citrus leaves. We were able to collect up to 39
      volatiles from both juvenile and mature leaves. Our results indicated that
      juvenile leaves produced both monoterpenes and sesquiterpenes, and while mature
      leaves continued to produce a variety of monoterpenes, their release of
      sesquiterpenes decreased dramatically. The finding that juvenile leaves emitted
      higher levels of sesquiterpenes while mature leaves released mostly monoterpenes
      suggests that younger leaves of plants may be involved in a more complex chemical
      communication system.

PMID- 27889521
TI  - Azacytidine and miR156 promote rooting in adult but not in juvenile Arabidopsis
      tissues.
AB  - Poor adventitious root (AR) formation is a major obstacle in micropropagation and
      conventional vegetative propagation of many crops. It is affected by many
      endogenous and exogenous factors. With respect to endogenous factors, the phase
      change from juvenile to adult has a major influence on AR formation and rooting
      is usually much reduced or even fully inhibited in adult tissues. It has been
      reported that the phase change is characterized by an increase in DNA-methylation
      and a decrease in the expression of microRNA156 (miR156). In this paper, we
      examined the effect of azacytidine (AzaC) and miR156 on AR formation in adult and
      juvenile Arabidopsis tissues. To identify the ontogenetic state researchers have
      used flowering or leaf morphology. We have used the rootability which allows - in
      contrast with both other characteristics- to examine the ontogenetic state at the
      cellular level. Overexpression of miR156 promoted only the rooting of adult
      tissues indicating that the phase change-associated loss in tissues' competence
      to develop ARs is also under the control of miR156. Azacytidine inhibits DNA
      methylation during DNA replication. Azacytidine treatment also promoted AR
      formation in nonjuvenile tissues but had no or little effect in juvenile tissues.
      Its addition during seedling growth (by which all tissues become hypomethylated)
      or during the rooting treatment (by which only those cells become hypomethylated
      that are generated after taking the explant) are both effective in the promotion
      of rooting. An AzaC treatment may be useful in tissue culture for crops that are
      recalcitrant to root.

PMID- 27889522
TI  - Increased sink strength offsets the inhibitory effect of sucrose on sugarcane
      photosynthesis.
AB  - Spraying sucrose inhibits photosynthesis by impairing Rubisco activity and
      stomatal conductance (gs), whereas increasing sink demand by partially darkening
      the plant stimulates sugarcane photosynthesis. We hypothesized that the
      stimulatory effect of darkness can offset the inhibitory effect of exogenous
      sucrose on photosynthesis. Source-sink relationship was perturbed in two
      sugarcane cultivars by imposing partial darkness, spraying a sucrose solution
      (50mM) and their combination. Five days after the onset of the treatments, the
      maximum Rubisco carboxylation rate (Vcmax) and the initial slope of A-Ci curve
      (k) were estimated by measuring leaf gas exchange and chlorophyll fluorescence.
      Photosynthesis was inhibited by sucrose spraying in both genotypes, through
      decreases in Vcmax, k, gs and ATP production driven by electron transport (Jatp).
      Photosynthesis of plants subjected to the combination of partial darkness and
      sucrose spraying was similar to photosynthesis of reference plants for both
      genotypes. Significant increases in Vcmax, gs and Jatp and marginal increases in
      k were noticed when combining partial darkness and sucrose spraying compared with
      sucrose spraying alone. Our data also revealed that increases in sink strength
      due to partial darkness offset the inhibition of sugarcane photosynthesis caused
      by sucrose spraying, enhancing the knowledge on endogenous regulation of
      sugarcane photosynthesis through the source-sink relationship.

PMID- 27889523
TI  - Identification of target genes and processes involved in erucic acid accumulation
      during seed development in the biodiesel feedstock Pennycress (Thlaspi arvense
      L.).
AB  - We studied erucic acid accumulation in the biodiesel feedstock Pennycress
      (Thlaspi arvense L.) as a first step towards the development of a sustainable
      strategy for biofuel production in the EU territory. To that end, two inbred
      Pennycress lines of European origin, "NASC" and "French," were cultivated in a
      controlled chamber and in experimental field plots, and their growth, seed
      production and seed oil characteristics analyzed. Differences in some agronomical
      traits like vernalization (winter-French versus spring-NASC), flowering time
      (delayed in the French line) and seed production (higher in the French line) were
      detected. Both lines showed a high amount (35-39%) of erucic acid (22:1Delta13)
      in their seed oil. Biochemical characterization of the Pennycress seed oil
      indicated that TAG was the major reservoir of 22:1Delta13. Incorporation of
      22:1Delta13 to TAG occurred very early during seed maturation, concomitant with a
      decrease of desaturase activity. This change in the acyl fluxes towards
      elongation was controlled by different genes at different levels. TaFAE1 gene,
      encoding the fatty acid elongase, seemed to be controlled at the transcriptional
      level with high expression at the early stages of seed development. On the
      contrary, the TaFAD2 gene that encodes the Delta12 fatty acid desaturase or
      TaDGAT1 that catalyzes TAG biosynthesis were controlled post-transcriptionally.
      TaWRI1, the master regulator of seed-oil biosynthesis, showed also high
      expression at the early stages of seed development. Our data identified genes and
      processes that might improve the biotechnological manipulation of Pennycress
      seeds for high-quality biodiesel production.

PMID- 27889524
TI  - Early responses of mature Arabidopsis thaliana plants to reduced water potential
      in the agar-based polyethylene glycol infusion drought model.
AB  - Drought is one of the most important environmental stressors resulting in
      increasing losses of crop plant productivity all over the world. Therefore,
      development of new approaches to increase the stress tolerance of crop plants is
      strongly desired. This requires precise and adequate modeling of drought stress.
      As this type of stress manifests itself as a steady decrease in the substrate
      water potential (psiw), agar plates infused with polyethylene glycol (PEG) are
      the perfect experimental tool: they are easy in preparation and provide a
      constantly reduced psiw, which is not possible in soil models. However,
      currently, this model is applicable only to seedlings and cannot be used for
      evaluation of stress responses in mature plants, which are obviously the most
      appropriate objects for drought tolerance research. To overcome this limitation,
      here we introduce a PEG-based agar infusion model suitable for 6-8-week-old A.
      thaliana plants, and characterize, to the best of our knowledge for the first
      time, the early drought stress responses of adult plants grown on PEG-infused
      agar. We describe essential alterations in the primary metabolome (sugars and
      related compounds, amino acids and polyamines) accompanied by qualitative and
      quantitative changes in protein patterns: up to 87 unique stress-related proteins
      were annotated under drought stress conditions, whereas further 84 proteins
      showed a change in abundance. The obtained proteome patterns differed slightly
      from those reported for seedlings and soil-based models.

PMID- 27889525
TI  - Nano-scale elastic-plastic properties and indentation-induced deformation of
      single crystal 4H-SiC.
AB  - The nanoscale elastic-plastic response of single crystal 4H-SiC has been
      investigated by nanoindentationwith a Berkovich tip. The hardness (H) and elastic
      modulus (E) determined in the load-independent region were 36+/-2GPa and 413+/
      8GPa, respectively. The indentation size effect (ISE) of hardness within an
      indentation depth of 60nm was systematically analyzed by the Nix-Gao model. Pop
      in events occurring at a depth of ~23nm with indentation loads of 0.60-0.65mN
      were confirmed to indicate the elastic-plastic transition of the crystal, on the
      basis of the Hertzian contact theory and Johnson's cavity model. Theoritically
      calculated maximum tensile strength (13.5GPa) and cleavage strength (33GPa) also
      affirms the deformation due to the first pop-in rather than tensile stresses.
      Further analyses of deformation behavior across the indent was done in 4H-SiC by
      a combined technique of focused ion beam and transmission electron microscope,
      revealing that slippage occurred in the (0001) plane after indentation.

PMID- 27889526
TI  - Strain shielding in trabecular bone at the tibial cement-bone interface.
AB  - Aseptic loosening of the tibial component remains the leading cause for revision
      surgery in total knee arthroplasty (TKA). Understanding the mechanisms leading to
      loss of fixation can offer insight into preventative measures to ensure a longer
      survival rate. In cemented TKA, loosening occurs at the cement-trabecular
      interface probably due to a stress-shielding effect of the stiffer implant
      material in comparison with bone. Using finite element models of lab-prepared
      tibial cement-trabeculae interface specimens (n=4) based on micro-CT images, this
      study aims to investigate the micromechanics of the interlock between cement and
      trabecular bone. Finite element micromotion between cement and trabeculae and
      bone strain were compared in the interdigitated trabeculae as well as strain in
      the bone distal to the interface. Lab-prepared specimens and their FE models were
      assumed to represent the immediate post-operative situation. The cement layer was
      removed in the FE models while retaining the loading conditions, which resulted
      in FE models that represented the pre-operative situation. Results showed that
      micromotion and bone strain decrease when interdigitation depth increases. Bone
      cement micromotion and bone strain at the distal interdigitated region showed a
      dependence on bone volume fraction. Comparing the immediate post-operative and
      pre-operative situations, trabeculae embedded deep within the cement generally
      showed the highest level of strain-shielding. Strain shielding of interdigitated
      bone, in terms of reduction in compressive strains, was found to be between 35
      and 61 % for the four specimens. Strain adaptive remodeling could thus be a
      plausible mechanism responsible for loss of interdigitated bone.

PMID- 27889527
TI  - 177Lu-DOTATATE treatment in neuroendocrine tumours. A preliminary study.
AB  - Therapy with radiolabelled somatostatin analogue peptides is a promising new
      therapy to treat neuroendocrine tumours. The aim of this preliminary study is to
      present our experience with 177Lu-DOTATATE therapy, and evaluate tolerability and
      short-term efficacy in patients with tumours expressing somatostatin receptors. A
      total of 7 patients with metastatic neuroendocrine tumours were treated, each
      with 4 doses of 177Lu-DOTATATE. The treatment response was evaluated in the form
      of biochemical response (tumour markers), imaging methods (somatostatin receptor
      scintigraphy, computed tomography, and magnetic resonance), and functional and
      quality of life responses using the Karnofsky performance status scale. Treatment
      toxicity was also evaluated. The results obtained were as follows: Biochemical
      response: 60% of patients showed tumour marker levels returning to normal, while
      they decreased significantly in the remaining 40%. Imaging response: 85.7% had a
      partial response, while 14.3% showed stable disease. All (100%) patients showed a
      significant improvement in quality of life, with increased Karnofsky scale
      scores. No patient had acute or chronic toxicity, and subacute transient
      haematological toxicity was observed in 42.8% of patients. Despite being a
      preliminary study, it was found that treatment with 177Lu-DOTATATE is a safe
      treatment with few side effects, and an objective response was achieved in most
      patients.

PMID- 27889528
TI  - Tailoring shape and size of biogenic silver nanoparticles to enhance
      antimicrobial efficacy against MDR bacteria.
AB  - Spherical, rectangular, penta, and hexagonal silver nanoparticles of different
      dimensions were biosynthesized in an eco-friendly manner by biocontrol agent,
      Trichoderma viride by manipulating physical parameters, pH, temperature, and
      reaction time. The particles were characterized by UV-vis spectroscopy; Dynamic
      Light Scattering (DLS), Transmission Electron Microscopy (TEM) and Fourier
      Transform Infra-red Spectroscopy (FTIR). Shape and size dependent antimicrobial
      activity of nanoparticles against human pathogens was observed. Maximum
      inhibition was found with spherical nanoparticles (2-5 nm) showing 40, 51, 43,
      53.9 and 55.8% against Shigella sonnei, Escherichia coli, Serratia marcescens,
      Staphylococcus. aureus and Pseudomonas aeruginosa respectively, where as
      pentagonal and hexagonal nanoparticles (50-100 nm) demonstrated 32, 41, 31, 42.84
      and 42.80% of inhibition as compared to control. Nanoparticles of different
      geometry and dimension established enhanced antagonistic activity against
      pathogens with all the tested antibiotics. Excellent antimicrobial efficacy was
      obtained with spherical nanoparticles of 2-5 nm with ampicillin and penicillin.
      Shape and size played major role in enhancing antimicrobial potential of silver
      nanoparticles, both singly and synergistically with antibiotics which can be
      exploited to combat the spread of multidrug resistant pathogens.

PMID- 27889529
TI  - Antiviral activities of selected antimalarials against dengue virus type 2 and
      Zika virus.
AB  - In a previous study, twelve antimalarial compounds, amodiaquine (AQ) and
      derivatives, were shown to have potent anti-dengue viral (DENV) activity by using
      the stable DENV2 Renilla luciferase reporter replicon expressing BHK-21 cells,
      infectivity (plaque), and the qRT-PCR assays. In this study, we performed
      molecular modeling on these compounds to determine their stereo-electronic
      properties required for optimal antiviral activity. Based on the similarity of
      calculated stereo-electronic profiles, specifically the electrostatic potential
      profiles of the compounds, and in silico screening of related compounds from
      literature, we identified three additional compounds, Quinacrine (QC), Mefloquine
      (MQ), and GSK369796. Analysis of their antiviral activities indicated that all
      three compounds have high anti-DENV activity in the DENV2 replicon expressing
      cells with EC50 values of 5.30 +/- 1.31 MUM (QC), 3.22 +/- 0.37 MUM (MQ), and
      5.06 +/- 0.86 MUM (GSK369796). The infectivity assays revealed the EC50 values of
      7.09 +/- 1.67 MUM (QC), 4.36 +/- 0.31 MUM (MQ) and 3.03 +/- 0.35 MUM (GSK369796).
      The mode of action of these compounds is through inhibition of autophagy, thereby
      affecting DENV2 replication. Moreover, these compounds also showed antiviral
      activity against the rapidly emerging Zika virus (ZIKV) with EC50 values of 2.27
      +/- 0.14 MUM (QC), 3.95 +/- 0.21 MUM (MQ), and 2.57 +/- 0.09 MUM (GSK369796).

PMID- 27889530
TI  - Identification of proximal biomarkers of PKC agonism and evaluation of their role
      in HIV reactivation.
AB  - DESIGN: The HIV latent CD4+ T cell reservoir is broadly recognized as a barrier
      to HIV cure. Induction of HIV expression using protein kinase C (PKC) agonists is
      one approach under investigation for reactivation of latently infected CD4+ T
      cells (Beans et al., 2013; Abreu et al., 2014; Jiang et al., 2014; Jiang and
      Dandekar, 2015). We proposed that an increased understanding of the molecular
      mechanisms of action of PKC agonists was necessary to inform on biological
      signaling and pharmacodynamic biomarkers. RNA sequencing (RNA Seq) was applied to
      identify genes and pathways modulated by PKC agonists. METHODS: Human CD4+ T
      cells were treated ex vivo with Phorbol 12-myristate 13-acetate, prostatin or
      ingenol-3-angelate. At 3 h and 24 h post-treatment, cells were harvested and RNA
      Seq was performed on RNA isolated from cell lysates. The genes differentially
      expressed across the PKC agonists were validated by quantitative RT-PCR (qPCR). A
      subset of genes was evaluated for their role in HIV reactivation using siRNA and
      CRISPR approaches in the Jurkat latency cell model. RESULTS: Treatment of primary
      human CD4+ T cells with PKC agonists resulted in alterations in gene expression.
      qPCR of RNA Seq data confirmed upregulation of 24 genes, including CD69, Egr1,
      Egr2, Egr3, CSF2, DUSP5, and NR4A1. Gene knockdown of Egr1 and Egr3 resulted in
      reduced expression and decreased HIV reactivation in response to PKC agonist
      treatment, indicating a potential role for Egr family members in latency
      reversal. CONCLUSION: Overall, our results offer new insights into the mechanism
      of action of PKC agonists, biomarkers of pathway engagement, and the potential
      role of EGR family in HIV reactivation.

PMID- 27889531
TI  - SIRT1 protects cardiac cells against apoptosis induced by zearalenone or its
      metabolites alpha- and beta-zearalenol through an autophagy-dependent pathway.
AB  - Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several
      species of Fusarium in cereals and agricultural products. The major ZEN
      metabolites are alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL). In
      the present study, we investigated the underlying mechanism of the toxicity
      induced by ZEN, alpha-ZOL and beta-ZOL in cardiac cells (H9c2). We show that
      treatment with ZEN or its metabolites induces the activation of the mitochondrial
      pathway of apoptosis as characterized by an increase in ROS generation, a loss of
      mitochondrial transmembrane potential (DeltaPsim) and an activation of caspases.
      Besides, we demonstrate that these mycotoxins promote the activation of autophagy
      before the onset of apoptosis. Indeed, we observed that a short-time (6h)
      treatment with ZEN, alpha-ZOL or beta-ZOL, increased the level of Beclin-1 and
      LC3-II and induced the accumulation of the CytoID(r) autophagy detection probe.
      Moreover, the inhibition of autophagy by Chloroquine significantly increased cell
      death induced by ZEN, alpha-ZOL or beta-ZOL, suggesting that the activation of
      autophagy serves as a cardioprotective mechanism against these mycotoxins. In
      addition, we found that the inhibition (EX527) or the knockdown of SIRT1 (siRNA)
      significantly increased apoptosis induced by ZEN or its derivatives, whereas
      SIRT1 activation with RSV greatly prevents the cytotoxic effects of these
      mycotoxins. By contrast, when autophagy was inhibited by CQ, the activation of
      SIRT1 by RSV had no protection against the cardiotoxicity of ZEN or its
      metabolites, suggesting that SIRT1 protects cardiac cells by an autophagy
      dependent pathway.

PMID- 27889533
TI  - Temporomandibular Joint Disorder Management in Oral and Maxillofacial Surgery.
AB  - PURPOSE: This article discusses why the management of temporomandibular joint
      disorder (TMD) cases leads to some oral and maxillofacial surgeons to actively
      avoid attracting such patients to their practices, offers some evidence-based
      explanations, and provides recommendations for resolution that will benefit not
      only the specialty, but more importantly the patients it serves. MATERIALS AND
      METHODS: A review of the reasons some surgeons state they do not wish to manage
      TMD cases is presented, followed by an updated review of the TMD and orthopedic
      literature discussing not only the importance of a proper diagnosis but also the
      impact of comorbid conditions, genetics, clinical experience, and patient
      expectations important to achieving good TMD management outcomes. RESULTS: The
      literature shows that the frustration clinicians and TMD and orthopedic patients
      have had in the past are related to initial misdiagnosis leading to multiple
      failed procedures, failed materials and devices, failure to understand the impact
      of comorbid conditions and genetic features on outcomes, clinicians' experience
      in complex cases, and unrealistic outcomes expectations by the clinician and the
      patient. CONCLUSION: Although it is not reasonable to believe that every graduate
      of an oral and maxillofacial surgery residency will have an interest in
      management of TMD cases in their future practices, those who will must understand
      the importance of the issues of proper diagnosis, the relation of TMD patient
      comorbidities and prior management to final outcomes, honest awareness of their
      experience and ancillary support to manage complex cases, and how essential a
      realistic prognosis is to a successful outcome for the clinician and the patient.

PMID- 27889532
TI  - Characterisation of ZBTB46 and DC-SCRIPT/ZNF366 in rainbow trout, transcription
      factors potentially involved in dendritic cell maturation and activation in fish.
AB  - ZBTB46 and DC-SCRIPT/ZNF366 are two zinc finger transcription factors that play
      important roles in regulating differentiation of dendritic cells in mammals. In
      this study, the ZBTB46 and DC-SCRIPT/ZNF366 homologues were identified in rainbow
      trout Oncorhynchus mykiss and their expression analysed in vivo and in vitro. As
      transcription factors, they are well conserved in sequence, genomic organisation
      and gene synteny. Their expression was differentially modulated by bacterial and
      viral PAMPs in the monocyte/macrophage-like cell line RTS-11, in primary head
      kidney (HK) macrophages, and in HK macrophages cultured with IL-4/13A. In the RTS
      11 cells and primary HK macrophages, all the ZBTB46 and DC-SCRIPT/ZNF366
      homologues were down-regulated by interferon gamma (type II IFN) but unaffected
      by IFN2 (type I IFN), administered as recombinant proteins to cell cultures. In
      fish gills, infection with amoebae (Paramoebae perurans) resulted in reduction of
      ZBTB46 and DC-SCRIPT/ZNF366 expression in Atlantic salmon Salmo salar, whilst
      infection with Yersinia ruckeri induced gene expression in rainbow trout.

PMID- 27889534
TI  - Serum Annexin A2 Level Is Associated With Diagnosis and Prognosis in Patients
      With Oral Squamous Cell Carcinoma.
AB  - PURPOSE: In several human cancer types, serum annexin A2 levels are increased,
      but little is known regarding oral squamous cell carcinoma (OSCC). This study
      aimed to measure serum annexin A2 levels in OSCC patients and assess the
      association with diagnosis and prognosis. MATERIALS AND METHODS: This case
      control study compared serum annexin A2 concentrations in a group of OSCC
      patients and a control group. The predictor variable was the presence or absence
      of OSCC, and the outcome variable was the level of serum annexin A2. Annexin A2
      concentrations were measured with an enzyme-linked immunosorbent assay, and
      correlations with clinicopathologic characteristics of OSCC were further
      evaluated. Receiver operating characteristic (ROC) curves, Kaplan-Meier curves,
      log-rank analyses, and a Cox proportional hazards model were used to evaluate the
      diagnostic and prognostic value of annexin A2. RESULTS: Serum samples were taken
      from 399 individuals: 126 patients with OSCC (aged 62.7 +/- 10.6 years, 79 men
      and 47 women); 115 patients with benign oral disease (aged 63.9 +/- 10.8 years,
      73 men and 42 women); and 158 healthy controls (aged 65.4 +/- 12.8 years, 92 men
      and 66 women). The annexin A2 level was significantly higher in OSCC patients
      than in patients with benign disease and controls (27.1 +/- 9.81 ng/mL vs 15.9 +/
      6.97 ng/mL and 15.0 +/- 6.69 ng/mL, respectively). To distinguish OSCC patients
      from the other 2 groups, ROC curve-area under the ROC curve (AUC) analysis for
      serum annexin A2 levels provided an AUC of 0.80 (sensitivity, 0.62; specificity,
      0.87) and an AUC of 0.77 (sensitivity, 0.57; specificity, 0.89). Furthermore,
      OSCC patients with high annexin A2 levels had poorer overall survival.
      CONCLUSIONS: This study suggested that an elevated serum annexin A2 level might
      be a novel diagnostic and prognostic biomarker for OSCC patients.

PMID- 27889535
TI  - Does Temporomandibular Joint Pathology With or Without Surgical Management Affect
      the Stability of Counterclockwise Rotation of the Maxillomandibular Complex in
      Orthognathic Surgery? A Systematic Review and Meta-Analysis.
AB  - PURPOSE: This study was designed to determine the stability of counterclockwise
      rotation (CCWR) of the maxillomandibular complex (MMC) in orthognathic surgery
      with or without surgical correction of coexisting temporomandibular joint (TMJ)
      pathology. MATERIALS AND METHODS: The authors implemented a systematic review and
      meta-analysis. A search of major databases through PubMed, EMBASE, and Cochrane
      CENTRAL was performed. Inclusion criteria were studies that analyzed CCWR of the
      MMC in regard to skeletal stability after orthognathic surgery in patients with
      or without pre-existing TMJ pathology that was or was not surgically corrected
      concomitantly. The predictor variables were patients who underwent CCWR of the
      MMC in the following subgroups: 1) healthy TMJs (presumed healthy based on
      history, clinical evaluation, and radiographic analysis but without magnetic
      resonance imaging [MRI] confirmation), 2) no TMJ assessment, 3) untreated TMJ
      disc displacement (confirmed by MRI), 4) TMJ disc displacement (confirmed by MRI)
      repositioned using Mitek anchors, and 5) reconstruction with TMJ total joint
      prosthesis. Outcome variables were surgical relapse for angular and linear
      measurements. Postsurgical mean changes for the occlusal plane (OP) and linear
      measurements using a fixed-effects model with a 95% confidence interval were
      analyzed. RESULTS: A total of 345 patients enrolled in 12 studies were included
      in this study. There was significant OP relapse and horizontal relapse at the B
      point and menton for studies with untreated TMJ disc displacement and studies
      without TMJ assessment (P < .005). There was significant horizontal relapse at
      the A point for studies with healthy TMJs, without assessment of the TMJs, and
      with TMJ reconstruction with total joint prostheses (P < .005). There was no
      significant vertical relapse at the B and A points for all subgroup analyses (P <
      .005). CONCLUSION: The result of the meta-analysis suggests that CCWR of the MMC
      is a stable procedure for patients with healthy TMJs, patients undergoing
      concomitant TMJ disc repositioning with Mitek anchors, and patients with TMJ
      patient-fitted total joint prostheses but unstable in the presence of untreated
      TMJ disc displacements and when TMJ status is not assessed.

PMID- 27889536
TI  - Compact Integration of Multi-Network Topology for Functional Analysis of Genes.
AB  - The topological landscape of molecular or functional interaction networks
      provides a rich source of information for inferring functional patterns of genes
      or proteins. However, a pressing yet-unsolved challenge is how to combine
      multiple heterogeneous networks, each having different connectivity patterns, to
      achieve more accurate inference. Here, we describe the Mashup framework for
      scalable and robust network integration. In Mashup, the diffusion in each network
      is first analyzed to characterize the topological context of each node. Next, the
      high-dimensional topological patterns in individual networks are canonically
      represented using low-dimensional vectors, one per gene or protein. These vectors
      can then be plugged into off-the-shelf machine learning methods to derive
      functional insights about genes or proteins. We present tools based on Mashup
      that achieve state-of-the-art performance in three diverse functional inference
      tasks: protein function prediction, gene ontology reconstruction, and genetic
      interaction prediction. Mashup enables deeper insights into the structure of
      rapidly accumulating and diverse biological network data and can be broadly
      applied to other network science domains.

PMID- 27889537
TI  - Response to Letter to the Editor: Regarding "The dosimetric impact of image
      guided radiation therapy by intratumoral fiducial markers".

PMID- 27889539
TI  - Pharmacodynamics of S-dimethylarsino-glutathione, a putative metabolic
      intermediate of inorganic arsenic, in mice.
AB  - Inorganic arsenicals are well-known carcinogens, whereas arsenite (iAsIII)
      compounds are now recognized as potent therapeutic agents for several leukemias,
      and arsenic trioxide has been used for the treatment of recurrent acute
      promyelocytic leukemia (APL). However, recent clinical trials revealed that
      arsenite is not always effective for non-APL malignancies. Another arsenical, S
      dimethylarsino-glutathione ([DMAIII(GS)]), which is a putative metabolic
      intermediate in the hepatic metabolism of iAsIII, shows promise for treating
      several types of lymphoma. However, the metabolism of [DMAIII(GS)] has not been
      well investigated, probably because [DMAIII(GS)] is not stable in biological
      fluids where the concentration of glutathione is low. In the present study, we
      injected [DMAIII(GS)] intravenously into mice and compared the tissue
      distribution and metabolic dynamics of [DMAIII(GS)] with those of sodium arsenite
      (NaAsO2). We found a unique organ preference for the distribution of [DMAIII(GS)]
      to the lung and brain in comparison to NaAsO2. Furthermore, [DMAIII(GS)] appeared
      to bind to serum albumin by exchanging its glutathione moiety quickly after
      administration, providing novel insights into the longer retention of
      [DMAIII(GS)] in plasma.

PMID- 27889540
TI  - Seladoeflavones A-F, six novel flavonoids from Selaginella doederleinii.
AB  - Six new flavonoids, seladoeflavones A-F (1-6), were isolated from the whole herbs
      of Selaginella doederleinii, together with one known flavonoid (7). Their
      structures including absolute configuration were characterized on the basis of
      extensive spectroscopic methods including NMR, HRMS, and electronic circular
      dichroism (ECD). All compounds consist of an aryl substituent at the C-3'
      position of naringenin or apigenin skeletons, and compounds 1 and 6 were
      identified as R configurations, which are uncommonly encountered in nature. A
      possible biosynthetic pathway was postulated. In addition, bioassay of the
      isolates revealed that 5-7 exhibited moderate cytotoxicity against three human
      cancer cell lines NCI-H460, A549, and K562 in vitro with IC50 values ranging from
      8.17 to 18.66MUM.

PMID- 27889541
TI  - New monoterpenoid oxindole alkaloid derivatives from the stems of Uncaria hirsuta
      Havil. and their cytotoxicity and tandem mass spectrometric fragmentation.
AB  - Four new alkaloids, comprising three 3-oxo-3,7-seco-oxindole alkaloids
      (hirsutanine D-F, 1-3) and one oxindole alkaloid N-oxide (uncarine B N-oxide, 4),
      together with four known heteroyohimbine-type oxindole alkaloids, were isolated
      from the stems of Uncaria hirsuta Havil. Structures of 1-4 were elucidated by
      extensive NMR and HR-ESIMS data analyses. Compound 3 is the first 3-oxo-3,7-seco
      oxindole alkaloid with ring B opened and degraded isolated from the Uncaria
      genus. Compounds 1-3 exhibited slight inhibition effect on the proliferation of
      the breast cancer cell MDA-MB-231. The positive mode collision-induced
      dissociation of the 3-oxo-3,7-seco-oxindole alkaloids (1-3) was featured by the
      beta-cleavage and alpha-cleavage of the amido bond, while the N-oxide (4) showed
      characteristic neutral eliminations of .OH and H2O.

PMID- 27889542
TI  - a-Glucosidase inhibitors extracted from the roots of Polygonum multiflorum Thunb.
AB  - A novel stilbene glucoside, polygonumnolide D (1), and a novel dianthrone
      glycoside, polygonumnolide E (2), were isolated from a 70% EtOH extract of the
      dried roots of Polygonum multiflorum Thunb., together with six known compounds (3
      8). Their structures were elucidated by 1D and 2D NMR as well as mass
      spectroscopy data. The isolated compounds were evaluated for their a-glucosidase
      inhibitory activities in vitro. Compounds 1, 2 and 5 showed the inhibitory
      activity against a-glucosidase with the IC50 values of 2.4, 2.7 and 0.3MUM,
      respectively.

PMID- 27889544
TI  - Role of EUS in patients with suspected Barrett's esophagus with high-grade
      dysplasia or early esophageal adenocarcinoma: impact on endoscopic therapy.
AB  - BACKGROUND AND AIMS: Endoscopic therapy is the standard treatment for high-grade
      dysplasia and some cases of T1a esophageal adenocarcinoma (EAC), but it is not
      appropriate for deeply invasive disease. Data on the value of EUS for patient
      selection for endoscopic or surgical resection are conflicting. We investigated
      the outcome of esophageal EUS for the staging and treatment selection of patients
      with treatment-naive, premalignant Barrett's esophagus (BE) and suspected
      superficial EAC. METHODS: We retrospectively reviewed consecutive patients who
      underwent EUS for staging of treatment-naive, suspected premalignant BE and
      superficial EAC from January 2006 to June 2014. All patients referred for
      endoscopic therapy routinely underwent EUS. Patients with esophageal masses,
      squamous cell cancers, previous neoadjuvant therapy, or unrelated pathologies
      were excluded. Each patient's final diagnosis was verified by EMR, esophagectomy,
      or forceps biopsy sampling. Test characteristics of EUS were calculated. RESULTS:
      Three hundred thirty-five patients (mean age, 68 years; 86% male) with BE, a
      Prague C mean of 2.8 cm, and a Prague M mean of 4.5 cm were staged (pT0, 78% [6%
      nondysplastic, 24% low-grade dysplasia, 42% high-grade dysplasia]; pT1a, 14%;
      pT1b, 7%; and pT2, 1%). Sensitivity, specificity, positive predictive value,
      negative predictive value, and accuracy for patient selection to endoscopic
      (T1aN0 or less) or surgical therapy with EUS TN staging were 50%, 93%, 40%, 95%,
      and 90%, respectively. Comparable rates were achieved for patients with nodular
      BE. Overstaging occurred in 7% of patients, and EUS selected 11% for incorrect
      treatment modalities compared with pathologic staging. CONCLUSIONS: This study
      confirms the limited value of EUS suggested in the latest American College of
      Gastroenterology guidelines for BE management.

PMID- 27889543
TI  - EUS-guided fine-needle injection of gemcitabine for locally advanced and
      metastatic pancreatic cancer.
AB  - BACKGROUND AND AIMS: Among the greatest hurdles to pancreatic cancer (PC) therapy
      is the limited tissue penetration of systemic chemotherapy because of tumor
      desmoplasia. The primary study aim was to determine the toxicity profile of EUS
      guided fine-needle injection (EUS-FNI) with gemcitabine. Secondary endpoints
      included the ability to disease downstage leading to an R0 resection and overall
      survival (OS) at 6 months, 12 months, and 5 years after therapy. METHODS: In a
      prospective study from a tertiary referral center, gemcitabine (38 mg/mL) EUS-FNI
      was performed in patients with PC before conventional therapy. Initial and
      delayed adverse events (AEs) were assessed within 72 hours and 4 to 14 days after
      EUS-FNI, respectively. Patients were followed for >=5 years or until death.
      RESULTS: Thirty-six patients with stage II (n = 3), stage III (n = 20), or stage
      IV (n = 13) disease underwent gemcitabine EUS-FNI with 2.5 mL (.7-7.0 mg) total
      volume of injectate per patient. There were no initial or delayed AEs reported.
      Thirty-five patients (97.2%) were deceased at the time of analysis with a median
      10.3 months of follow-up (range, 3.1-63.9). OS at 6 months and 12 months was 78%
      and 44%, respectively. The median OS was 10.4 months (range, 2.7-68). Among
      patients with stage III unresectable disease, 4 (20%) were downstaged and
      underwent an R0 resection. CONCLUSIONS: Our study suggests the feasibility,
      safety, and potential efficacy of gemcitabine EUS-FNI for PC. Additional data are
      needed to verify these observations and to determine the potential role relative
      to conventional multimodality therapy.

PMID- 27889545
TI  - Comparison of carbon dioxide and air insufflation during consecutive EGD and
      colonoscopy in moderate-sedation patients: a prospective, double-blind,
      randomized controlled trial.
AB  - BACKGROUND AND AIMS: Endoscopy is performed with air insufflation and is usually
      associated with abdominal pain. It is well recognized that carbon dioxide (CO2)
      is absorbed more quickly into the body than air; however, to date, few studies
      have investigated the use of CO2 insufflation during consecutive EGD and
      colonoscopy (CEC). Thus, this study evaluated the efficacy of CO2 insufflation
      compared with air insufflation in CEC. METHODS: From March 2014 to April 2016, a
      total of 215 consecutive patients were randomly assigned to receive CO2
      insufflation (CO2 group, n = 108) or air insufflation (air group, n = 107).
      Abdominal pain after CEC was recorded on a visual analogue scale (VAS). The
      amount of sedatives administered, use of analgesics, polyp detection rate (PDR),
      adenoma detection rate (ADR), abdominal circumference, and adverse events were
      also analyzed. RESULTS: Baseline patient characteristics were not significantly
      different between the groups. Abdominal pain on the VAS in the CO2 group and air
      group 1 hour after CEC was, respectively, 13.8 and 20.1 (P = .010), 3 hours after
      CEC was 8.3 and 12.5 (P = .056), 6 hours after CEC was 3.5 and 5.3 (P = .246),
      and 1 day after CEC was 1.8 and 3.4 (P = .192). The dose of sedative
      administered, analgesic usage, PDR, ADR, and adverse events were not
      statistically different between the groups. However, the increase in abdominal
      circumference was significantly higher in the air group than in the CO2 group.
      CONCLUSIONS: CO2 insufflation was superior to air insufflation with regard to the
      pain score on the VAS in the hour after CEC. (Clinical trial registration number:
      KCT0001491.).

PMID- 27889546
TI  - Comparison of a split-dose bowel preparation with 2 liters of polyethylene glycol
      plus ascorbic acid and 1 liter of polyethylene glycol plus ascorbic acid and
      bisacodyl before colonoscopy.
AB  - BACKGROUND AND AIMS: Recently, a low-volume polyethylene glycol formulation
      containing ascorbic acid (PEG-Asc) has proven as safe and effective as
      traditional 4-L PEG solutions for colonoscopy preparation. However, currently
      available aqueous purgative formulations are poorly tolerated. The aim of this
      study was to compare a split-dose 2-L PEG-Asc formulation and a 1-L PEG-Asc
      formulation with bisacodyl (10 mg) to determine the quality of bowel cleansing
      and patient tolerability. METHODS: A single-center, randomized, observer-blinded
      study was performed between May 2015 and September 2015. Two hundred outpatients
      referred for colonoscopy were prospectively enrolled and assigned to either the
      split-dose 2-L PEG-Asc group or the 1-L PEG-Asc with bisacodyl 10-mg group. The
      Boston Bowel Preparation Scale (BBPS) and Aronchick Bowel Preparation Scale
      (ABPS) were used to evaluate bowel cleansing. The tolerability of the regimens
      and satisfaction of patients was determined based on a questionnaire. RESULTS:
      Two hundred patients received either 2-L PEG-Asc or 1-L PEG-Asc with bisacodyl.
      Regarding colon cleansing outcome (BBPS and ABPS), the 1-L PEG-Asc with bisacodyl
      group showed similar but non-inferior results compared with the 2-L PEG-Asc group
      on both BBPS (6.92 +/- 1.63 vs 6.57 +/- 1.37; P = .103) and ABPS (96% vs 95%; P =
      1.000) scales. Tolerability was similar for both 1-L PEG-Asc with bisacodyl and 2
      L PEG-Asc. CONCLUSIONS: 1-L PEG-Asc is a suitable alternative to low-volume bowel
      preparation for colonoscopy. Our study showed that the 1-L PEG-Asc plus bisacodyl
      preparation has comparable tolerability and results in adequate colon cleansing.
      Bowel preparation with bisacodyl and 1-L PEG-Asc is a suitable alternative to low
      volume bowel preparation for colonoscopy. (Clinical trial registration number:
      NCT02980562.).

PMID- 27889547
TI  - Clinical outcomes of non-curative endoscopic submucosal dissection with negative
      resected margins for gastric cancer.
AB  - BACKGROUND AND AIMS: There has been little information about the long-term
      outcomes of patients with early gastric cancer (EGC) treated by non-curative
      endoscopic submucosal dissection (ESD) with negative resected margins (R0
      resection). We aimed to compare the clinical outcomes of non-curative ESD with R0
      resection between patients who underwent additional gastrectomy and those who did
      not. METHODS: Among EGC patients treated by ESD from 2002 to 2010, 66 patients
      were treated by non-curative ESD with R0 resection. Patients received either
      additional gastrectomy (group A, n = 45) or were followed up without gastrectomy
      (group B, n = 21). The clinicopathologic findings and the subsequent clinical
      course were compared between the 2 groups. RESULTS: Patients in group A were
      younger than those in group B (68.0 vs 71.0 years, P = .006). The follow-up
      period was longer in group A than in group B (7.8 vs 5.9 years, P = .011). The
      percentage of patients who died of any cause was not statistically lower in group
      A than in group B (13.3% vs 33.3%, P = .06). Although the overall survival rate
      was higher in group A than in group B (93.3% vs 76.2%, P = .028), disease
      specific survival rates did not differ between the 2 groups (97.8% vs 100%, P =
      .495). A Cox proportional hazards model showed that gastrectomy was not an
      independent factor associated with overall survival. CONCLUSIONS: Careful follow
      up may be an alternative strategy to gastrectomy for a subgroup of patients
      treated by non-curative ESD with R0 resection.

PMID- 27889548
TI  - Impact of physician compliance with colonoscopy surveillance guidelines on
      interval colorectal cancer.
AB  - BACKGROUND AND AIMS: Interval colorectal cancer (iCRC) incidence is the criterion
      standard benchmark for measuring the effectiveness of colonoscopy. Colonoscopy
      surveillance guidelines are designed to minimize iCRC cases. Our aims were to
      describe characteristics of iCRC patients and to assess whether development of
      iCRC is related to colonoscopy surveillance guideline intervals. METHODS: We
      performed a retrospective cohort study of postcolonoscopy iCRC cases in a large
      healthcare system. Guideline-based colonoscopy intervals were calculated based on
      the 2012 U.S. Multi-Society Task Force for Colorectal Cancer colonoscopy
      surveillance guidelines. Backward stepwise linear regression was used to
      determine predictors of iCRC before guideline-recommended follow-up intervals.
      RESULTS: We identified 245 iCRC cases (mean age, 69.4 years; 56.3% male) out of
      5345 colon cancers evaluated for a prevalence of 4.60%. On index colonoscopy,
      75.1% had an adequate preparation, 93.0% reached the cecum, and 52.5% had polyps.
      iCRC developed before the guideline-recommended interval in 59.1% of patients
      (94/159). Independent predictive factors of this finding were inadequate
      preparation (OR, .012; 95% CI, .003-.06; P < .0001) and >=3 polyps on index
      colonoscopy (OR, .2; 95% CI, .078-.52; P = .0009). An endoscopist-recommended
      follow-up interval past the guideline-recommended interval was seen in 23.9% of
      cases (38/159). Most (34/38, 89.5%) of these iCRCs had inadequate preparation and
      were diagnosed after the guideline-based follow-up interval. CONCLUSIONS: Current
      colonoscopy surveillance guidelines may be inadequate to prevent many iCRC cases.
      Physician noncompliance with guideline-based surveillance intervals may increase
      in iCRC cases, especially in patients with an initially inadequate bowel
      preparation.

PMID- 27889549
TI  - Assessing arsenic and selenium in a single nail clipping using portable X-ray
      fluorescence.
AB  - The feasibility of measuring arsenic and selenium contents in a single nail
      clipping was investigated using a small-focus portable X-ray fluorescence (XRF)
      instrument with monochromatic excitation beams. Nail clipping phantoms
      supplemented with arsenic and selenium to produce materials with 0, 5, 10, 15,
      and 20ug/g were used for calibration purposes. In total, 10 different clippings
      were analyzed at two different measurement positions. Energy spectra were fit
      with detection peaks for arsenic Kalpha, selenium Kalpha, arsenic Kbeta, selenium
      Kbeta, and bromine Kalpha characteristic X-rays. Data analysis was performed
      under two distinct conditions of fitting constraint. Calibration lines were
      established from the amplitude of each of the arsenic and selenium peaks as a
      function of the elemental contents in the clippings. The slopes of the four
      calibration lines were consistent between the two conditions of analysis. The
      calculated minimum detection limit (MDL) of the method, when considering the
      Kalpha peak only, ranged from 0.210+/-0.002ug/g selenium under one condition of
      analysis to 0.777+/-0.009ug/g selenium under another. Compared with previous
      portable XRF nail clipping studies, MDLs were substantially improved for both
      arsenic and selenium. The new measurement technique had the additional benefits
      of being short in duration (~3min) and requiring only a single nail clipping. The
      mass of the individual clipping used did not appear to play a major role in
      signal strength, but positioning of the clipping is important.

PMID- 27889550
TI  - To infinity and beyond: Children generalize the successor function to all
      possible numbers years after learning to count.
AB  - Recent accounts of number word learning posit that when children learn to
      accurately count sets (i.e., become "cardinal principle" or "CP" knowers), they
      have a conceptual insight about how the count list implements the successor
      function - i.e., that every natural number n has a successor defined as n+1
      (Carey, 2004, 2009; Sarnecka & Carey, 2008). However, recent studies suggest that
      knowledge of the successor function emerges sometime after children learn to
      accurately count, though it remains unknown when this occurs, and what causes
      this developmental transition. We tested knowledge of the successor function in
      100 children aged 4 through 7 and asked how age and counting ability are related
      to: (1) children's ability to infer the successors of all numbers in their count
      list and (2) knowledge that all numbers have a successor. We found that children
      do not acquire these two facets of the successor function until they are about
      51/2 or 6years of age - roughly 2years after they learn to accurately count sets
      and become CP-knowers. These findings show that acquisition of the successor
      function is highly protracted, providing the strongest evidence yet that it
      cannot drive the cardinal principle induction. We suggest that counting
      experience, as well as knowledge of recursive counting structures, may instead
      drive the learning of the successor function.

PMID- 27889551
TI  - Endothelial dysfunction and cardiovascular risk factors in childhood acute
      lymphoblastic leukemia survivors.
AB  - BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) survivors have increased
      risk of obesity, metabolic alterations and cardiovascular disease (CVD). Vascular
      endothelial function has been studied in adult cancers. Limited data exist
      regarding CVD risk factors among childhood ALL survivors. We aimed to assess
      endothelial function, metabolic and cardiovascular risk factors in young
      survivors of childhood ALL. METHODS: Auxological parameters, blood pressure,
      glucose, lipid profile, hemostatic markers (total adiponectin and high-molecular
      weight subfraction, endothelin-1, von Willebrand factor antigen, thrombin
      antithrombin complex, D-dimers, fibrinogen), high sensitive C-reactive protein
      and ultrasound parameters of endothelial function (flow-mediated dilation-FMD,
      common carotid intima-media thickness-C-IMT, and antero-posterior diameter of
      infra-renal abdominal aorta-APAO) were assessed in 52 ALL survivors and 34 sex
      and age-matched controls. RESULTS: ALL patients and controls were not
      statistically different as regards body mass index and waist circumference. Blood
      pressure, glucose, total and LDL-cholesterol, triglycerides, high sensitive C
      reactive protein were statistically higher in ALL than in controls, while HDL
      cholesterol was lower in ALL than in controls. Patients showed statistically
      lower high-molecular-weight adiponectin and thrombin-antithrombin complex
      (p=0.003 and p<0.001, respectively) and higher vonWillebrand factor antigen
      (p=0.002) than controls. FMD was lower in patients than in controls (p<0.001).
      Biomarkers of endothelial function, systolic blood pressure and waist
      circumference were correlated to FMD. CONCLUSIONS: ALL survivors showed
      derangement of endothelial function, which likely occurs during chemotherapy and
      lasts till follow up. They showed metabolic alterations even though obesity was
      not documented. Endothelial vascular parameters should be evaluated earlier
      during follow-up to detect preclinical onset of CVD.

PMID- 27889552
TI  - Relation of red blood cell distribution width with CHADS2 and CHA2DS2-VASc score
      in Chinese patients with non-valvular atrial fibrillation.
AB  - BACKGROUND: Higher red cell distribution width (RDW) predicts adverse events in
      patients with cardiovascular diseases. However, there are limited data regarding
      the relationship between RDW and thromboembolism risk in the patients with atrial
      fibrillation (AF). We aimed to investigate the association between RDW and
      CHADS2, CHA2DS2-VASc scores used for the evaluation of thromboembolic risk in
      patients with non-valvular atrial fibrillation (AF). METHODS: Our study included
      99 patients with AF (68 paroxysmal AF; 31 persistent AF). We calculated CHADS2
      and CHA2DS2-VASc risk scores for each patient, and we carefully recorded clinical
      characteristics as well as laboratory and echocardiographic parameters. According
      to CHADS2 and CHA2DS2-VASc scores, we divided the AF patients into 2 groups (low
      intermediate risk and high risk group). Subsequently, we compared the
      aforementioned parameters between the 2 groups, and we evaluated the relationship
      between RDW and CHADS2/CHA2DS2-VASc score. Finally, multivariate logistic
      regression analysis was performed to find independent predictors of high CHADS2,
      CHA2DS2-VASc scores. RESULTS: Patients with high CHADS2, CHA2DS2-VASc scores had
      older age, higher RDW, and creatinine levels, increased left atrial diameter and
      lower left ventricular ejection fraction, compared to the low CHADS2, CHA2DS2
      VASc score group. Multivariate logistic regression analysis showed that RDW was
      an independent predictor for high CHADS2, CHA2DS2-VASc scores(OR: 2.184 and OR:
      5.748; all P<0.05). CONCLUSION: RDW is significantly correlated with CHADS2 and
      CHA2DS2-VASc score in the patients with AF, while is an independent predictor for
      high CHADS2 and CHA2DS2-VASc score.

PMID- 27889553
TI  - Long term outcomes from catheter ablation of very longstanding persistent atrial
      fibrillation.
AB  - INTRODUCTION: Success rates for catheter ablation of longstanding persistent
      atrial fibrillation (AF) are significantly poorer than for recently persistent or
      paroxysmal forms. We report on single centre long term outcomes from ablation of
      very longstanding (> 2years) persistent AF. MATERIAL AND METHODS: A retrospective
      analysis of outcomes for patients undergoing catheter ablation for symptomatic
      very longstanding persistent AF between 2008 and 2013 was performed. RESULTS:
      Twenty-nine patients were followed for a mean of 61+/-15months following the
      index ablation procedure. The mean duration of persistent AF prior was 64+/
      51months (range 24-200), mean age 61+/-6years and mean CHA2DS2-VASc score 1.1+/
      1.2. Antral pulmonary vein electrical isolation only was performed in 14 (48%)
      with the remainder having additional lines and/or CFAE ablation also. At last
      follow-up 24 (83%) were in sinus rhythm but only 9 (31%) remained free of
      detectable arrhythmia, 25 (86%) were taking antiarrhythmic therapy and 18 (62%)
      required intermittent DC cardioversions. The mean time to first AF recurrence was
      14+/-14months (range 2-48). Redo ablation was required in 13 (45%) at a mean
      follow-up time of 15+/-12months. The mean EHRA score improved from 3.5+/-0.5 to
      1.4+/-0.4 (p<0.0001). CONCLUSIONS: The vast majority (83%) of very longstanding
      persistent AF patients maintained sinus rhythm at a mean follow-up time of 5years
      following catheter ablation, associated with a significant improvement in symptom
      scores. Adjunctive therapies including antiarrhythmics, DC cardioversions and
      redo ablation were required in most patients.

PMID- 27889554
TI  - Familial dilated cardiomyopathy: A multidisciplinary entity, from basic screening
      to novel circulating biomarkers.
AB  - Idiopathic dilated cardiomyopathy has become one of the most prevalent inherited
      cardiomyopathies over the past decades. Genetic screening of first-degree
      relatives has revealed that 30-50% of the cases have a familial origin. Similar
      to other heart diseases, familial dilated cardiomyopathy is characterized by a
      high genetic heterogeneity that complicates family studies. Cli'nical screening,
      12-lead electrocardiogram and transthoracic echocardiogram are recommended for
      patients and first-degree family members. Magnetic resonance also needs to be
      considered. Genetic technologies have become fundamental for the clinical
      management of this disease. New generation sequencing methods have made genetic
      testing feasible for extensive panels of genes related to the disease. Recently,
      new imaging modalities such as speckle-tracking, strain and strain rate or
      magnetic resonance, and circulating biomarkers such as non-coding RNAs, have
      emerged as potential strategies to help cardiologists in their clinical practice.
      Imaging, genetic and blood-based techniques should be considered together in the
      evaluation and testing of familial dilated cardiomyopathy. Here, we discuss the
      current procedures and novel approaches for the clinical management of familial
      dilated cardiomyopathy.

PMID- 27889555
TI  - Correlation between microvascular dysfunction and B-type natriuretic peptide
      levels in non-ischemic heart failure patients with cardiac fibrosis.
AB  - BACKGROUNDS: The relationship between microvascular dysfunction and plasma B-type
      natriuretic peptide (BNP) levels remains unclear in heart failure (HF) patients
      with cardiac fibrosis. METHODS: This study evaluated 55 consecutive non-ischemic
      HF patients in an effort to determine the relationship between endothelial
      independent coronary microvascular dysfunction and plasma BNP levels, as well as
      whether each measure is correlated with myocardial fibrosis. We evaluated plasma
      BNP levels in patients with stable HF. We used cardiac catheterization to measure
      trans-cardiac BNP release levels, measuring from the coronary sinus and the
      aortic root, and coronary flow reserve (CFR). Patients also underwent cardiac
      magnetic resonance imaging to evaluate for the presence of late gadolinium
      enhancement (LGE), as an indicator of cardiac fibrosis. RESULTS: CFR in cardiac
      catheterization was significantly and inversely correlated with plasma BNP levels
      (r=0.336, p=0.012) and trans-cardiac BNP release levels (r=0.347, p=0.041).
      Thirty-three patients were LGE-positive. CFR was significantly correlated with
      plasma BNP levels in the LGE-positive group (r=0.349, p=0.046), but this
      correlation was not significant in the LGE-negative group. (r=0.338, p=0.125).
      Multivariate logistic regression analysis revealed that a plasma BNP levels
      >180pg/ml at stable HF condition was significant and independent predictor of
      CFR<2.5 in all patients (p=0.035, odds ratio: 5.2, 95% confidence interval: 1.1
      29.0), and in the LGE-positive group (p=0.040, odds ratio: 5.4, 95% confidence
      interval: 1.1-27.2). CONCLUSIONS: In non-ischemic HF patients especially those
      with cardiac fibrosis, endothelial independent microvascular dysfunction is
      closely correlated with plasma BNP levels, and ventricular wall tension.

PMID- 27889556
TI  - Compact bone-derived mesenchymal stem cells attenuate nonalcoholic
      steatohepatitis in a mouse model by modulation of CD4 cells differentiation.
AB  - Increasing evidence has accrued which indicates that mesenchymal stem cells
      (MSCs) have a potential clinical value in the treatment of certain diseases.
      Globally, nonalcoholic steatohepatitis (NASH) is a widespread disorder. In the
      present study, MSCs were isolated successfully from compact bone and a mouse
      model of NASH was established as achieved with use of a methionine-choline
      deficient (MCD) diet. Compact bone-derived MSCs transplantation reduced MCD diet
      induced weight loss, hepatic lipid peroxidation, steatosis, ballooning, lobular
      inflammation and fibrogenesis. It was shown that MSCs treatment hampered MCD diet
      induced proliferation of CD4+ IFN-gamma+ and CD4+IL-6+ T spleen cells. In
      addition, CD4+IL-17+ lymphocytes that associated with anti-inflammation show
      little change in MCD as well as in MCD+MSCs splenocytes. We conclude that MSCs
      may have a potential clinical value upon NASH, through their capacity to suppress
      activation of CD4+ IFN-gamma+ and CD4+IL-6+ lymphocytes.

PMID- 27889557
TI  - Identification of a hemolin protein from Actias selene mediates immune response
      to pathogens.
AB  - Hemolins play an important role in development and innate immunity in insects. In
      this study, a hemolin cDNA of 1412bp in Actias selene (As-HEM) was isolated and
      its open reading frames (ORFs) were 420 amino acid residues. Sequence analysis
      indicated As-HEM was homologous to those hemolins from other insects species. The
      recombinant protein of As-HEM was expressed in Escherichia coli, and anti-As-HEM
      antibodies were prepared. Real-time quantitative PCR (RT-qPCR) and western blot
      results revealed that mRNA and protein levels of As-HEM were mostly detected in
      hemocytes and hemolymph. Immune challenge assays showed that both the mRNA and
      protein levels of As-HEM could be induced significantly post Beauveria bassiana,
      E. coli, Micrococcus luteus and nuclear polyhedrosis virus challenges.
      Agglutination assays revealed that recombinant As-HEM could promote the
      agglutination of E. coli in the presence of calcium. Our results suggested that
      As-HEM was involved in the innate immunity of A. selene.

PMID- 27889558
TI  - The periosteal microcirculation in health and disease: An update on clinical
      significance.
AB  - Apart from its nutritive functions, the periosteum critically affects bone
      regeneration via its stem/osteoprogenitor cell content. Normal healing after bone
      fractures, trauma-orthopedic interventions and invasive dental procedures is
      critically linked to the reestablishment of the periosteal microcirculation, but
      the reconstruction, replacement or repair of lost tissues may also be performed
      with autologous periosteum. Besides the initiation of cell differentiation during
      bone repair and remodeling processes, the periosteum together with the endosteum
      plays significant roles in the pathogenesis of both hormone-related and trauma
      induced osteoporotic alterations in the bone metabolism. Nevertheless, the axial
      bones, and in particular the jawbones, and the appendicular bones display
      differences not only in their blood supply and fracture healing characteristics,
      but also in respect of the development of osteoporosis and their reactions to
      treatment modalities (i.e. bisphosphonates). These reactions may also be linked
      to the differences in periosteal microcirculatory reactions. The present overview
      summarizes the relevant data of microcirculatory studies focusing on the
      periosteal reactions in different anatomical locations together with the optimal
      background methodologies, study models and the most significant observations.

PMID- 27889559
TI  - Plasma endothelial microparticles reflect the extent of capillaroscopic
      alterations and correlate with the severity of skin involvement in systemic
      sclerosis.
AB  - INTRODUCTION AND AIM: Endothelial microparticles (EMPs) are membrane-coated
      vesicles shed from endothelial cells and are considered markers of the
      endothelial state. It has been shown that total numbers of circulating EMPs are
      increased in patients with systemic sclerosis (SSc), but their clinical
      correlations have not yet been investigated in detail. We aimed to assess
      possible relationships between circulating EMPs and clinical as well as
      laboratory features among SSc patients with special attention to possible
      association with alteration in microvascular morphology objectified on nailfold
      videocapillaroscopy and clinical signs of microvascular complications. MATERIALS
      AND METHODS: The study included 47 SSc patients and 27 age- and sex-matched
      healthy controls. EMPs were identified with flow cytometry after staining
      platelet-poor plasma with combinations of fluorescent cell-specific monoclonal
      antibodies (anti-CD31, -51, -42b, -62E and Annexin V). The following types of
      EMPs were evaluated: total EMPs (CD31+/CD42b-), activated EMPs (CD62E+/AnnV-,)
      and apoptotic EMPs (CD62E+/AnnV+ or CD51+). Clinical evaluation of patients was
      obtained, including nailfold videocapillaroscopy. RESULTS: All types of EMPs were
      significantly elevated in SSc patients as compared with healthy controls. We
      found significant inverse correlation between severity of skin involvement and
      values of total EMPs (r=-0.32; p=0.02) and their levels tended to be lower in SSc
      patients with digital ulcers when compared to those without ischaemic skin
      lesions (p=0.09). Total EMPs and activated EMPs showed correlations with the
      number of ramified capillaries (r=-0.40 and r=0.37, respectively, p<0.05 for
      both). Moreover, total EMPs inversely correlated with the severity of capillary
      loss (r=-0.35, p<0.05) and their levels were significantly lower in patients with
      late NVC pattern with respect to those with early microangiopathy (p<0.05). On
      the other hand, active NVC pattern was characterized by strongly elevated levels
      of activated EMPs when compared to an early vascular alteration (p<0.05).
      CONCLUSIONS: Our results suggest that quantity and phenotype of circulating EMPs
      might indicate on molecular vascular damage with endothelial dysfunction and to
      reflect progressive loss of capillaries consequencing in microvascular
      insufficiency in SSc patients.

PMID- 27889560
TI  - MicroRNA let-7g inhibited hypoxia-induced proliferation of PASMCs via G0/G1 cell
      cycle arrest by targeting c-myc.
AB  - AIMS: Pulmonary hypertension (PH) is a proliferative disorder characterized by
      enhanced proliferation and suppressed apoptosis of intrapulmonary vascular smooth
      muscle cells. Recently, network-based bioinformatics have identified let-7
      family, a tumor suppressive microRNA, regulate multiple interacting targets
      relevant to PH. However, the role of let-7 in vascular homeostasis in PH remains
      unknown. Thus, we wanted to investigate the role of let-7 in hypoxia-induced
      PASMCs proliferation and the underlying mechanism in hypoxic pulmonary
      hypertension (HPH). MAIN METHODS: The male Sprague-Dawley (SD) rats were exposed
      to hypoxia (10% O2) for 21days to induce HPH. The expression of let-7 was
      determined by quantitative real-time polymerase chain reaction (qRT-PCR) and in
      situ hybridization. Primary rat PASMCs were exposed to hypoxia (3% O2). MTS and
      EDU were performed to evaluate PASMCs proliferation. The mRNA and protein
      expression of c-myc, Bmi-1 and p16 were determined by qRT-PCR and Western
      blotting, respectively. The functions of let-7g on PASMCs proliferation, c-myc,
      Bmi-1 and p16 expression were assessed by let-7g mimic and inhibitor
      transfection. KEY FINDINGS: Among let-7 family members, only let-7b and let-7g
      were significantly down-regulated in remodeled pulmonary artery in HPH rats.
      Furthermore, only let-7g level was decreased in hypoxic PASMCs. Either hypoxia or
      let-7g inhibitor stimulated proliferation of PASMCs, let-7g mimic inhibited
      hypoxia-induced PASMCs proliferation. C-myc was the target of let-7g in PASMCs.
      Transfect of let-7g mimic inhibited hypoxia-induced c-myc, Bmi-1 up-regulation
      and p16 down-regulation, which ultimately controls cell cycle progression.
      SIGNIFICANCE: Loss of inhibition on c-myc-Bmi-1-p16 signaling pathway by let-7g
      may lead to PASMCs proliferation and vascular remodeling in HPH.

PMID- 27889561
TI  - Inhibition of interleukin-5 induced false positive anti-drug antibody responses
      against mepolizumab through the use of a competitive blocking antibody.
AB  - Mepolizumab, a humanized IgG1 monoclonal antibody that blocks native homodimeric
      interleukin-5 (IL-5) from binding to the IL-5 receptor, has recently been
      approved for treatment of severe eosinophilic asthma. Our initial immunogenicity
      assay method for phase I and II studies utilized a bridging
      electrochemiluminescence format with biotin and ruthenium-labelled mepolizumab
      linked by anti-drug antibodies (ADA). We discovered that IL-5 significantly
      increased in dosed subjects from a phase II study and that the increased IL-5 was
      in the form of a drug-bound complex. We demonstrated that the elevated drug-bound
      IL-5 produced false-positive response in the in vitro ADA assay, in which drug
      bound IL-5 dissociated and then bridged mepolizumab conjugates to yield positive
      signal. To eliminate the IL-5 interference, we compared two strategies: a solid
      phase immunodepletion of IL-5 and an in-solution IL-5 immunocompetition. We
      identified the best competitive antibody for each purpose. We found both methods
      demonstrated similar effectiveness in reducing the false positive signal in IL-5
      spiked samples; however, the in-solution immunocompetition for IL-5 had fewer
      false positives in study samples. Additionally, the in-solution immunocompetition
      method was experimentally simpler to execute. We modified the ADA assay by adding
      a pre-treatment step with a mepolizumab competitive anti- IL-5 antibody. Using
      this new method, we retested clinical samples from two phase II studies
      (MEA112997 and MEA114092). The confirmed ADA positive incidence was reduced from
      29% and 61% to 1% and 8% with the modified in-solution immune inhibition method.
      Target interference is a fairly common problem facing immunogenicity testing, and
      target-induced false positive cannot be distinguished from true ADA response by
      the commonly used drug competitive confirmation assay. The approach and method
      used here for resolving target interference in ADA detection will be useful for
      differentiating between a true ADA response and target induced false positive as
      well as similar challenges in other programs.

PMID- 27889562
TI  - Systematic evaluation of monoclonal antibodies and immunoassays for the detection
      of Interferon-gamma and Interleukin-2 in old and new world non-human primates.
AB  - Non-human primates (NHP) provide important animal models for studies on immune
      responses to infections and vaccines. When assessing cellular immunity in NHP,
      cytokines are almost exclusively analyzed utilizing cross-reactive anti-human
      antibodies. The functionality of antibodies has to be empirically established for
      each assay/application as well as NHP species. A rational approach was employed
      to identify monoclonal antibodies (mAb) cross-reactive with many NHP species.
      Panels of new and established mAbs against human Interferon (IFN)-gamma and
      Interleukin (IL)-2 were assessed for reactivity with eukaryotically expressed
      recombinant IFN-gamma and IL-2, respectively, from Old (rhesus, cynomolgus and
      pigtail macaques, African green monkey, sooty mangabey and baboon) and New World
      NHP (Ma's night monkey, squirrel monkey and common marmoset). Pan-reactive mAbs,
      recognizing cytokines from all NHP species, were further analyzed in capture
      assays and flow cytometry with NHP peripheral blood mononuclear cells (PBMC). Pan
      reactive mAb pairs for IFN-gamma well as IL-2 were identified and used in ELISA
      to measure IFN-gamma and IL-2, respectively, in Old and New World NHP PBMC
      supernatants. The same mAb pairs displayed high functionality in ELISpot and
      FluoroSpot for the measurement of antigen-specific IFN-gamma and IL-2 responses
      using cynomolgus PBMC. Functionality of pan-reactive mAbs in flow cytometry was
      also verified with cynomolgus PBMC. The development of well-defined immunoassays
      functional with a panel of NHP species facilitates improved analyses of cellular
      immunity and enables inclusion in multiplex cytokine assays intended for a
      variety of NHP.

PMID- 27889563
TI  - Parent and peer pathways linking childhood experiences of abuse with marijuana
      use in adolescence and adulthood.
AB  - INTRODUCTION: The social developmental processes by which child maltreatment
      increases risk for marijuana use are understudied. This study examined
      hypothesized parent and peer pathways linking preschool abuse and sexual abuse
      with adolescent and adult marijuana use. METHODS: Analyses used data from the
      Lehigh Longitudinal Study. Measures included child abuse (physical abuse,
      emotional abuse, domestic violence, and neglect) in preschool, sexual abuse up to
      age 18, adolescent (average age=18years) parental attachment and peer marijuana
      approval/use, as well as adolescent and adult (average age=36years) marijuana
      use. RESULTS: Confirming elevated risk due to child maltreatment, path analysis
      showed that sexual abuse was positively related to adolescent marijuana use,
      whereas preschool abuse was positively related to adult marijuana use. In support
      of mediation, it was found that both forms of maltreatment were negatively
      related to parental attachment, which was negatively related, in turn, to having
      peers who use and approve of marijuana use. Peer marijuana approval/use was a
      strong positive predictor of adolescent marijuana use, which was a strong
      positive predictor, in turn, of adult marijuana use. CONCLUSIONS: Results support
      social developmental theories that hypothesize a sequence of events leading from
      child maltreatment experiences to lower levels of parental attachment and, in
      turn, higher levels of involvement with pro-marijuana peers and, ultimately, to
      both adolescent and adult marijuana use. This sequence of events suggests
      developmentally-timed intervention activities designed to prevent maltreatment as
      well as the initiation and progression of marijuana use among vulnerable
      individuals.

PMID- 27889564
TI  - Interactive pathways to substance abuse.

PMID- 27889565
TI  - A terminal antibody method based on multiple factors that influence ELISA results
      for measurement of antibody affinity in clinical specimens.
AB  - OBJECTIVE: To establish a new method for the measurement of antibody affinity in
      clinical samples. METHODS: Serial dilutions of antiserum samples were prepared to
      find the threshold concentration of antibody separating detectable from negative
      ELISA results. This threshold concentration was defined as the terminal antibody
      (TA) concentration, and a new method for measuring antibody affinity based on the
      effect of multiple factors that influence ELISA results at TA concentration was
      established, which we called the TA method. The TA method was used to measure low
      and high-affinity antiserum samples to verify the validity of the method, and
      then was used to measure the affinity of the antibody to Hepatitis B surface
      antigen and affinity of antibody to Hepatitis C Virus in clinical serum
      specimens. RESULTS: Low- and high-affinity antiserum samples could be clearly
      distinguished by TA method. The antibody affinity in anti-HBe positive group was
      significantly higher than that of anti-HBe negative group; the affinity of
      antibody to HCV in HCV-RNA negative group was significantly higher than that of
      HCV-RNA positive group. CONCLUSIONS: The TA method for measuring antibody
      affinity in clinical specimens displayed its validation and that may have
      potential application value in clinical settings.

PMID- 27889566
TI  - Pitfalls in the detection of N-methyl-d-aspartate-receptor (NMDA-R) antibodies.

PMID- 27889567
TI  - Prognostic value of plasma apelin concentrations at admission in patients with ST
      segment elevation acute myocardial infarction.
AB  - BACKGROUND: The use of plasma biomarkers is relevant for the prognosis of ST
      segment elevation myocardial infarction (STEMI) patients. Apelin, an
      adipocytokine, plays a pivotal role in the pathophysiology of both
      ischemia/reperfusion injury and its potential subsequent heart failure. We
      evaluated apelin concentrations at admission as a biomarker to assess risk of 6
      month mortality. METHODS: Consecutive patients with STEMI were recruited from
      January 2012 to January 2013 (n=250). Plasma apelin, brain natriuretic peptide
      (BNP) and sensitive troponin I (sTnI) were assessed in EDTA-plasma samples
      obtained at admission. Clinical, hemodynamic and other laboratory variables were
      also registered. All-cause mortality was assessed at 6-month follow-up. RESULTS:
      Increased plasma apelin concentrations at admission were predictive of 6- month
      mortality, after adjustment for age, diabetes, systolic blood pressure, heart
      rate, glomerular filtration rate, Killip class, left ventricular ejection
      fraction, BNP and sTnI. The combination of apelin with BNP and sTnI further
      improved the apelin predictive value. Finally, apelin concentrations were
      associated with markers of ischemic heart failure severity, but not with markers
      of ischemic insult severity. CONCLUSIONS: Increased plasma concentrations of
      apelin at admission in patients with STEMI were associated with a higher risk of
      mortality at 6months, adding prognostic value to the provided by BNP. Moreover,
      apelin levels were also related to markers of ischemic heart failure severity,
      but not markers of ischemia severity.

PMID- 27889568
TI  - FosB regulates expression of miR-22 during PMA induced differentiation of K562
      cells to megakaryocytes.
AB  - Expression of many miRNAs is altered in different cancers and these changes are
      thought to play a key role in formation and progression of cancer. In chronic
      myelogenous leukemia (CML) a number of miRNAs are known to be down regulated as
      compared to normal cells. In this report we have investigated the mechanism of
      this down regulation by using PMA induced differentiation of CML cell line K562
      to megakaryocytes as an experimental system. On treatment with PMA, expression of
      many down regulated miRNAs including miR-22 is induced. PMA also induces
      expression of several transcription factors, including FosB, EGR1 and EGR2. Our
      results using a number of approaches, such as promoter reporter assay, FosB knock
      down and Chip assay, suggest that the expression of miR-22 is regulated
      transcriptionally by FosB.

PMID- 27889569
TI  - An evaluation of transit procurement training.
AB  - We evaluated a training course called "Orientation to Transit Procurement",
      designed and conducted by the National Transit Institute. This course is designed
      to provide Federal Transit Administration (FTA) grantees an overview of
      regulations and best practices related to the procurement process. Our objective
      in conducting the evaluation was to understand how transit agency staff made
      changes in procurement practices in response to the course training. The
      evaluation was mixed mode: an Internet survey followed by in-depth interviews
      with a small group of respondents. Survey respondents were also provided with an
      open-ended question providing us with additional context for our evaluation.
      Results show that the training is substantially successful at meeting the goal of
      improving procurement practices at transit agencies; indeed, most respondents
      report making changes at their agencies as the proximate result of the training.
      This was at odds with our exploration of knowledge of procurement topics, as most
      respondents gave inaccurate answers on multiple-choice "knowledge questions".
      This may have been due to question structure or, more likely, the nature of
      online surveys. Suitable training on the procurement of information technology
      was also a main concern. The lack of training in this area is indicative of the
      broader challenge facing public transit agencies in how to incorporate new forms
      of technology into their existing practices and bureaucratic structures.

PMID- 27889571
TI  - "New" Cancer Genes and Inherited Colorectal Cancer Risk: Caveat Emptor.

PMID- 27889570
TI  - Inhibitor of Apoptosis Protein-1 Regulates Tumor Necrosis Factor-Mediated
      Destruction of Intestinal Epithelial Cells.
AB  - BACKGROUND AND AIMS: Tumor necrosis factor (TNF) is a cytokine that promotes
      inflammation and contributes to pathogenesis of inflammatory bowel diseases.
      Unlike other cells and tissues, intestinal epithelial cells undergo rapid cell
      death upon exposure to TNF, by unclear mechanisms. We investigated the roles of
      inhibitor of apoptosis proteins (IAPs) in the regulation of TNF-induced cell
      death in the intestinal epithelium of mice and intestinal organoids. METHODS: RNA
      from cell lines and tissues was analyzed by quantitative polymerase chain
      reaction, protein levels were analyzed by immunoblot assays. BIRC2 (also called
      cIAP1) was expressed upon induction from lentiviral vectors in young adult mouse
      colon (YAMC) cells. YAMC cells, the mouse colon carcinoma cell line MC38, the
      mouse macrophage cell line RAW 264.7, or mouse and human organoids were incubated
      with second mitochondrial activator of caspases (Smac)-mimetic compound LCL161 or
      recombinant TNF-like weak inducer of apoptosis (TNFSF12) along with TNF, and cell
      death was quantified. C57BL/6 mice with disruption of Xiap, Birc2 (encodes
      cIAP1), Birc3 (encodes cIAP2), Tnfrsf1a, or Tnfrsf1b (Tnfrsf1a and b encode TNF
      receptors) were injected with TNF or saline (control); liver and intestinal
      tissues were collected and analyzed for apoptosis induction by cleaved caspase 3
      immunohistochemistry. We also measured levels of TNF and alanine aminotransferase
      in serum from mice. RESULTS: YAMC cells, and mouse and human intestinal
      organoids, died rapidly in response to TNF. YAMC and intestinal crypts expressed
      lower levels of XIAP, cIAP1, cIAP2, and cFLIP than liver tissue. Smac-mimetics
      reduced levels of cIAP1 and XIAP in MC38 and YAMC cells, and Smac-mimetics and
      TNF-related weak inducer of apoptosis increased TNF-induced cell death in YAMC
      cells and organoids-most likely by sequestering and degrading cIAP1. Injection of
      TNF greatly increased levels of cell death in intestinal tissue of cIAP1-null
      mice, compared with wild-type C57BL/6 mice, cIAP2-null mice, or XIAP-null mice.
      Excessive TNF-induced cell death in the intestinal epithelium was mediated TNF
      receptor 1. CONCLUSIONS: In a study of mouse and human cell lines, organoids, and
      tissues, we found cIAP1 to be required for regulation of TNF-induced intestinal
      epithelial cell death and survival. These findings have important implications
      for the pathogenesis of TNF-mediated enteropathies and chronic inflammatory
      diseases of the intestine.

PMID- 27889572
TI  - SMAD About Hepatitis C Virus Cell Entry and Liver Disease.

PMID- 27889573
TI  - How to Prepare for and Write a Grant: Personal Perspectives.

PMID- 27889574
TI  - Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic
      Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis.
AB  - BACKGROUND & AIMS: Pharmacologic treatment of eosinophilic esophagitis (EoE) is
      limited to off-label use of corticosteroids not optimized for esophageal
      delivery. We performed a randomized, controlled phase 2 trial to assess the
      ability of budesonide oral suspension (BOS), a novel muco-adherent topical
      steroid formulation, to reduce symptoms and esophageal eosinophilia in
      adolescents and adults with EoE. METHODS: In this multicenter, randomized, double
      blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages
      of 11 and 40 years with dysphagia and active esophageal eosinophilia were
      randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co
      primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from
      baseline, and proportion of patients with a histologic response (<=6
      eosinophils/high-power field) after treatment. Endoscopic severity scores and
      safety parameters were assessed. RESULTS: At baseline, mean DSQ scores were 29.3
      and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and
      placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and
      mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P
      < .05 for all). For BOS vs placebo, change in DSQ score was -14.3 vs -7.5 (P =
      .0096), histologic response rates were 39% vs 3% (P < .0001), and change in
      endoscopic severity score was -3.8 vs 0.4 (P < .0001). Adverse events were
      similar between groups. CONCLUSIONS: Treatment with BOS was well tolerated in
      adolescent and young adult patients with EoE and resulted in improvement in
      symptomatic, endoscopic, and histologic parameters using validated outcome
      instruments. ClinicalTrials.gov ID NCT01642212.

PMID- 27889575
TI  - Isthmus Time Is Here: Runx1 Identifies Mucosal Stem Cells in the Gastric Corpus.

PMID- 27889576
TI  - Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through
      2012.
AB  - BACKGROUND & AIMS: The incidence and mortality of hepatocellular carcinoma (HCC)
      have been reported to be plateauing in the United States. The United States has
      large racial, ethnic, and regional variation; we collected data from all 50
      states to better analyze changes in HCC incidence in the entire United States.
      METHODS: We collected data from the US Cancer Statistics registry, which covers
      97% of the population, and calculated adjusted incidence rates. We assessed
      annual trends among sociodemographic and geographic subgroups using joinpoint
      analysis. RESULTS: HCC incidence increased from 4.4/100,000 in 2000 to
      6.7/100,000 in 2012, increasing by 4.5% (95% confidence interval [CI], 4.3%-4.7%)
      annually between 2000 and 2009, but only by 0.7% annually (95% CI, -0.2% to 1.6%)
      from 2010 through 2012. The average annual percentage change (AAPC) between 2000
      and 2012 was higher in men (increase, 3.7%) than in women (increase, 2.7%), and
      highest in 55- to 59-year-old individuals (AAPC, 8.9%; 95% CI, 7.1%-10.7%) and 60
      to 64-year-old individuals (AAPC, 6.4%; 95% CI, 4.7%-8.2%). By 2012, rates in
      Hispanics surpassed those in Asians, and rates in Texas surpassed those in Hawaii
      (9.71/100,000 vs 9.68/100,000). Geographic variation within individual race and
      ethnic groups was observed, but rates were highest in all major race and ethnic
      groups in Texas. CONCLUSIONS: In an analysis of the incidence of HCC in all 50 US
      states, we found the rate of increase in HCC to have slowed from 2010 through
      2012. However, incidence is increasing in subgroups such as men ages 55 to 64
      years old-especially those born in the peak era of hepatitis C virus infection
      and among whites/Caucasians. Rates in Hispanics have surpassed those in Asian
      Americans. We observed geographic differences, with Texas having the highest age
      adjusted HCC rates nationwide.

PMID- 27889577
TI  - Brain uptake and metabolism of the endocannabinoid anandamide labeled in either
      the arachidonoyl or ethanolamine moiety.
AB  - INTRODUCTION: Anandamide (N-arachidonoylethanolamine) is a retrograde
      neuromodulator that activates cannabinoid receptors. The concentration of
      anandamide in the brain is controlled by fatty acid amide hydrolase (FAAH), which
      has been the focus of recent drug discovery efforts. Previous studies in C57BL/6
      mice using [3H-arachidonoyl]anandamide demonstrated deposition of tritium in
      thalamus and cortical areas that was blocked by treatment with an FAAH inhibitor
      and that was not seen in FAAH-knockout mice. This suggested that long chain fatty
      acid amides radiolabeled in the fatty acid moiety might be useful as ex vivo and
      in vivo radiotracers for FAAH, since labeled fatty acid released by hydrolysis
      would be rapidly incorporated into phospholipids with long metabolic turnover
      periods. METHODS: Radiotracers were administered intravenously to conscious Swiss
      Webster mice, and radioactivity concentrations in brain areas was quantified and
      radiolabeled metabolites determined by radiochromatography. RESULTS:
      [14C]Arachidonic acid, [14C-arachidonoyl]anandamide and [14C
      ethanolamine]anandamide, and also [14C]myristic acid, [14C
      myristoyl]myristoylethanolamine and [14C-ethanolamine]myristoyl-ethanolamine all
      had very similar distribution patterns, with whole brain radioactivity
      concentrations of 2-4% injected dose per gram. Pretreatment with the potent
      selective FAAH inhibitor URB597 did not significantly alter distribution patterns
      although radiochromatography demonstrated that the rate of incorporation of label
      from [14C]anandamide into phospholipids was decreased. Pretreatment with the
      muscarinic agonist arecoline which increases cerebral perfusion increased brain
      uptake of radiolabel from [14C]arachidonic acid and [14C-ethanolamine]anandamide,
      and (in dual isotope studies) from the unrelated tracer [125I]RTI-55.
      CONCLUSIONS: Together with our previously published study with [18F-palmitoyl]16
      fluoro-palmitoylethanolamine, the data show that the primary determinant of brain
      uptake for these tracers in Swiss-Webster mice is initial distribution according
      to blood flow. It is possible that recently reported strain differences in long
      chain fatty acid trafficking between C57BL/6 and Swiss-Webster mice are
      responsible for the differences between our results using [14C]anandamide and the
      earlier studies using [3H]anandamide.

PMID- 27889578
TI  - Molecular neurobiology of mTOR.
AB  - Mammalian/mechanistic target of rapamycin (mTOR) is a serine-threonine kinase
      that controls several important aspects of mammalian cell function. mTOR activity
      is modulated by various intra- and extracellular factors; in turn, mTOR changes
      rates of translation, transcription, protein degradation, cell signaling,
      metabolism, and cytoskeleton dynamics. mTOR has been repeatedly shown to
      participate in neuronal development and the proper functioning of mature neurons.
      Changes in mTOR activity are often observed in nervous system diseases, including
      genetic diseases (e.g., tuberous sclerosis complex, Pten-related syndromes,
      neurofibromatosis, and Fragile X syndrome), epilepsy, brain tumors, and
      neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, and
      Huntington's disease). Neuroscientists only recently began deciphering the
      molecular processes that are downstream of mTOR that participate in proper
      function of the nervous system. As a result, we are gaining knowledge about the
      ways in which aberrant changes in mTOR activity lead to various nervous system
      diseases. In this review, we provide a comprehensive view of mTOR in the nervous
      system, with a special focus on the neuronal functions of mTOR (e.g., control of
      translation, transcription, and autophagy) that likely underlie the contribution
      of mTOR to nervous system diseases.

PMID- 27889579
TI  - Protective effects of high Tryptophan diet on aging-induced passive avoidance
      impairment and hippocampal apoptosis.
AB  - In our previous work we have shown that L-Tryptophan (TrP) enriched diet prevents
      the age-induced decline of hippocampal Serotonin (5-HT) production. Considering
      that loss or reduction in 5-HT neurotransmission may contribute to age-related
      cognitive decline, here we have investigated the effect of such diet on passive
      avoidance (PA) behavior, cell death, pro- and anti- apoptotic molecules (BAX, Bcl
      2 and Caspase-3) and an important transcription factor involved in synaptic
      plasticity and memory (CREB). The increase in 5-HT neurotransmission in the
      Hippocampus (Hp) of aged rats was induced by 1 month of high TrP administration.
      In the first phase of our study we found that high TrP diet improves PA behaviour
      of aged rats and this correlated with a decrease of TUNEL positive cells in all
      hippocampal regions tested (CA1, CA2, CA3, DG). Interestingly, the Hp of aged
      animals fed with high TrP diet showed a significant downregulation of
      proapoptotic proteins, caspase-3 and BAX, and an increase of antiapoptotic
      molecules Bcl-2 as indicated by Western Blot and immunohistochemical analyses.
      Also, high TrP diet partially rescued the age-induced inhibition of hippocampal
      CREB phosphorylation. Altogether, our data suggest that enhanced TrP intake, and
      in consequence a potential increase in 5-HT neurotransmission, might be
      beneficial in preventing age-related detrimental features by inhibition of
      hippocampal apoptosis.

PMID- 27889580
TI  - Methylphenidate modulates dorsal raphe neuronal activity: Behavioral and neuronal
      recordings from adolescent rats.
AB  - Methylphenidate (MPD) is a widely prescribed psychostimulants used for the
      treatment of attention deficit hyperactive disorder (ADHD). Unlike the
      psychostimulants cocaine and amphetamine, MPD does not exhibit direct actions on
      the serotonin transporter, however there is evidence suggesting that the
      therapeutic effects of MPD may be mediated in part by alterations in serotonin
      transmission. This study aimed to investigate the role of the dorsal raphe (DR)
      nucleus, one of the major sources of serotonergic innervation in the mammalian
      brain, in the response to MPD exposure. Freely behaving adolescent rats
      previously implanted bilaterally with permanent electrodes were used. An open
      field assay and a wireless neuronal recording system were used to concomitantly
      record behavioral and DR electrophysiological activity following acute and
      chronic MPD exposure. Four groups were used: one control (saline) and three
      experimental groups treated with 0.6, 2.5, and 10.0mg/kg MPD respectively.
      Animals received daily MPD or saline injections on experimental days 1-6,
      followed by 3 washout days and MPD rechallenge dose on experimental day (ED)10.
      The same chronic dose of MPD resulted in either behavioral sensitization or
      tolerance, and we found that neuronal activity recorded from the DR neuronal
      units of rats expressing behavioral sensitization to chronic MPD exposure
      responded significantly differently to MPD rechallenge on ED10 compared to the DR
      unit activity recorded from animals that expressed behavioral tolerance. This
      correlation between behavioral response and DR neuronal activity following
      chronic MPD exposure provides evidence that the DR is involved in the acute
      effects as well as the chronic effects of MPD in adolescent rats.

PMID- 27889581
TI  - Handling of hazardous drugs - Effect of an innovative teaching session for
      nursing students.
AB  - BACKGROUND: Imparting knowledge and practical skills in hazardous drug handling
      in nursing students' education is essential to prevent hazardous exposure and to
      preserve nurses' health. OBJECTIVES: This study aimed at comparing routine
      nursing education with an additional innovative teaching session. DESIGN: A
      prospective controlled study in nursing students was conducted in two study
      periods: (i) a status-quo period (routine education on handling hazardous drugs)
      followed by (ii) an intervention period (additional innovative teaching session
      on handling hazardous drugs). SETTINGS/PARTICIPANTS: Nursing students at a
      vocational school were invited to participate voluntarily. METHODS: In both study
      periods (i) and (ii), the following factors were analysed: (a) knowledge of
      hazardous drug handling by questionnaire, (b) practical skills in hazardous drug
      handling (e.g. cleaning) by a simulated handling scenario, (c) contamination with
      drug residuals on the work surface by fluorescent imaging. RESULTS: Fifty-three
      nursing students were enrolled. (a) Median knowledge improved from status-quo
      (39% right answers) to intervention (65%, p<0.001), (b) practical skills improved
      from status-quo (53% of all participants cleaned the work surface) to
      intervention (92%, p<0.001). (c) Median number of particles/m2 decreased from
      status-quo to intervention (932/97, p<0.001). CONCLUSIONS: Compared with routine
      education, knowledge and practical skills in hazardous drug handling were
      significantly improved after an innovative teaching session. Additionally, the
      amount of residuals on the work surface decreased. This indicates a lower risk
      for hazardous drug exposure.

PMID- 27889582
TI  - The Chinese version of Instrument of Professional Attitude for Student Nurses
      (IPASN): Assessment of reliability and validity.
AB  - BACKGROUND: Professional attitude is of great importance for nursing talents in
      the modern society. To develop an effective educational program for student
      nurses in China, an appropriate instrument is required for the assessment of
      their professional attitude. OBJECTIVE: To assess the validity and reliability of
      the Instrument of Professional Attitude for Student Nurses (IPASN) in Chinese
      version. METHODS: The original version of IPASN was translated through Brislin
      model (translation, back translation, culture adaption and pilot study) with the
      authorization from the developer. A total of 681 nursing students were chosen by
      stratified convenience sampling to assess construct validity using exploratory
      factor analysis (EFA). Besides, item analysis, Cronbach's alpha coefficients,
      test-retest reliability were conducted to test the psychometric properties in
      this part. A total of 204 nursing undergraduate trainees were selected by cluster
      convenience sampling to confirm the structure using confirmatory factor analysis
      (CFA) in another time. RESULTS: Corrected item-total correlations, alpha if item
      deleted were between 0.33 and 0.69, 0.906 and 0.913, respectively, indicating no
      item should be deleted. Cronbach alpha value was 0.91 for the total scale and
      Cronbach alpha coefficient for subscales ranged from 0.67 to 0.89. Test-retest
      reliability estimated from intraclass correlation coefficient (ICC) was 0.74
      (P<0.05). Differences in item scores between the high-score group (the first 27%)
      and low-score group (the last 27%) were significant (P<0.001), indicating that
      the item discrimination ability was good. Seven subscales (contribution to
      increase of scientific information load, autonomy, community service, continuous
      education, to promote professional development, cooperation and theory guiding
      practice) were identified in EFA and confirmed in CFA, and explained 65.5% of the
      total variance. CONCLUSION: It indicated that the Chinese version of IPASN was
      valid and reliable for the evaluation of nursing students' professional attitude.

PMID- 27889583
TI  - Development and evaluation of a clinical simulation for new graduate nurses: A
      multi-site pilot study.
AB  - BACKGROUND: New nursing graduates have revealed that they perceive a gap between
      theory and practice with reference to their education and the real workplace
      setting. Additionally, many nurses experience a reality shock when they
      participate in clinical practice. PURPOSE: The purpose of this study was to
      develop and test the effects of a scenario-based simulation training program on
      new graduate nurses' competency, critical thinking dispositions, and
      interpersonal communication skills. METHOD: This pilot multi-site study used a
      pretest-posttest control group design. It was conducted at four sites of a
      university-affiliated simulation center in Korea. Participants were recruited
      utilizing a convenience sample from four tertiary hospitals in Korea. Twenty-four
      new graduate nurses participated in this study. RESULTS: At the three-month
      follow-up, the levels of communication skills used in practice among the
      intervention group were statistically significantly higher than those of the
      control group participants (U=151.50, p=.005). However, there were no significant
      differences between the groups in changes in nursing competency (U=287.50,
      p=.992) or critical thinking disposition scores (U=269.50, p=.702). The
      participants' mean rating scores concerning the objectives, intentions, and
      recommendations for other nurses were positive and high. CONCLUSION: The
      involvement of current practicing of nursing in certain scenarios and the
      implementation of simulation learning could enhance the readiness of new graduate
      nurses.

PMID- 27889584
TI  - Stress, resilience and psychological well-being in Chinese undergraduate nursing
      students.
AB  - BACKGROUND: Globally, stress is a well-recognized feature of the life of
      undergraduate nursing students. However, there currently is little evidence to
      suggest what role resilience plays in this issue. OBJECTIVES: To examine the
      relationship between stress and resilience on psychological well-being in a
      cohort of Chinese undergraduate student nurses. DESIGN/PARTICIPANTS: A cross
      sectional study was conducted using multivariate logistic regression and
      descriptive statistical analysis in three Chinese nursing schools. A total of
      1538 nursing students participated in the study, completing three validated self
      administered questionnaires. RESULTS: Nursing students in their final year
      reported the highest mean General Health Questionnaire 12 (GHQ-12) scores (Mean
      4.50 SD 2.89) and Stress in Nursing Student (SINS CN) scores (Mean 105.11 SD
      25.37), Moderate levels of resilience were noted across all four years of nursing
      training programmes (Mean 121.59 SD 21.49). Resilience scale (RS) scores were
      negatively correlated with mean total score for stress (r=-0.236, P<0.01) and
      negatively correlated with psychological well-being (r=-0.411, P<0.01).
      CONCLUSION: Psychological well-being appears impaired in Chinese nursing
      students, particularly final year students, prior to registration. Globally, more
      attention could be given to the potential role of resilience training and other
      forms effective coping strategies to deal with the inevitable sources of stress
      in student nurse training.

PMID- 27889585
TI  - Devices and dressings to secure peripheral venous catheters: A Cochrane
      systematic review and meta-analysis.
AB  - BACKGROUND: Peripheral venous catheterisation is the most frequent invasive
      procedure performed in hospitalised patients; yet over 30% of peripheral venous
      catheters fail before treatment ends. OBJECTIVES: To assess the effects of
      peripheral venous catheter dressings and securement devices on the incidence of
      peripheral venous catheter failure. DATA SOURCES: We searched the Cochrane Wounds
      Group Register, The Cochrane Central Register of Controlled Trials, MEDLINE;
      EMBASE and CINAHL for any randomised controlled trials comparing different
      dressings or securement devices used to stabilise peripheral venous catheters.
      The reference lists of included studies were also searched for any previously
      unidentified studies. RESULTS: We included six randomised controlled trials (1539
      participants) that compared various dressings and securement devices (transparent
      dressings versus gauze; bordered transparent dressings versus a securement
      device; bordered transparent dressings versus tape; and transparent dressing
      versus sticking plaster). Trial sizes ranged from 50 to 703 participants. The
      quality of evidence ranged from low to very low. Catheter dislodgements or
      accidental removals were lower with transparent dressings compared with gauze
      (two studies, 278 participants, risk ratio (RR) 0.40; 95% confidence interval
      (CI) 0.17-0.92, P=0.03%). However, the relative effects of transparent dressings
      and gauze on phlebitis (RR 0.89; 95% CI 0.47-1.68) and infiltration (RR 0.80; 95%
      CI 0.48-1.33) are unclear. A single study identified less frequent dislodgement
      or accidental catheter removal with bordered transparent dressings compared to a
      securement device (RR 0.14, 95% CI 0.03-0.63) but more phlebitis with bordered
      dressings (RR 8.11, 95% CI 1.03-64.02). A comparison of a bordered transparent
      dressing and tape found more peripheral venous catheter failure with the bordered
      dressing (RR 1.84, 95% CI 1.08-3.11) but the relative effect on dislodgement was
      unclear. CONCLUSIONS: There is no strong evidence to suggest that any one
      dressing or securement product for preventing peripheral venous catheter failure
      is more effective than any other product. All of the included trials were small,
      had high or unclear risk of bias for one or more of the quality elements we
      assessed, and wide confidence intervals, indicating that further randomised
      controlled trials are necessary. There is a need for suitably powered, high
      quality trials to evaluate the newer, high use products and novel - but expensive
      - securement methods, such as surgical grade glue.

PMID- 27889586
TI  - Surfactant effect on the physicochemical characteristics of cationic solid lipid
      nanoparticles.
AB  - Solid lipid nanoparticles (SLNs) may be considered as a new approach for
      therapeutics for many diseases. In addition to drug delivery, their use as non
      viral vectors for gene delivery can be obtained by including cationic lipids,
      which provide a positive surface potential that favors binding to the nucleic
      acids as DNA, siRNA, miRNA, etc. In fact, the addition of cationic surfactants is
      indispensable for obtaining nanoparticles with surface positive charge. In this
      study, three different cationic lipids (dioctadecyl dimethyl ammonium bromide,
      cetyltrimethyl ammonium bromide, cetylpyridinium chloride) and Brij 76 as
      nonionic surfactant were employed to formulate Precirol ATO 5 based cSLN using
      pEGFP-LUC as model plasmid. The physicochemical properties of cSLN were
      influenced by both type and amount of surfactants. Thermal analyses of bulk cSLN
      showed endothermic peaks significantly different from the ones of the single pure
      components, hinting a complete entanglement of the lipid matrix with the
      surfactants and justifying the different behavior of the cSLN in the ability to
      interact with the plasmid DNA. Finally, the biocompatibility of cSLN was
      demonstrated by hemolytic assays. These results may give an insight into the
      choice of surfactants in order to obtain non-toxic and highly effective delivery
      systems for gene therapy.

PMID- 27889587
TI  - Pharmaceutical technology can turn a traditional drug, dexamethasone into a first
      line ocular medicine. A global perspective and future trends.
AB  - Dexamethasone is one of the most prescribed glucocorticoids. It is effective and
      safe in the treatment of a wide variety of ocular conditions, including anterior
      and posterior segment inflammation. However, its half-life in the vitreous humor
      is very short, which means that it typically requires frequent administrations,
      thus reducing patient adherence and causing therapeutic failure. Innovative
      dexamethasone delivery systems have been designed in an attempt to achieve
      sustained release and targeting. The FDA has approved dexamethasone implants for
      the treatment of macular edema secondary to retinal vein occlusion and posterior
      segment noninfectious uveitis. Lenses, micro- and nanoparticles, liposomes,
      micelles and dendrimers are also proving to be adequate systems for maintaining
      optimal dexamethasone levels in the site of action. Pharmaceutical technology is
      turning a classical drug, dexamethasone, into a fashionable medicine.

PMID- 27889588
TI  - Preparation and properties evaluation of a novel pH-sensitive liposomes based on
      imidazole-modified cholesterol derivatives.
AB  - As a new kind of drug carries, pH-sensitive liposomes have been widely studied in
      tumor therapy for their advantages of target ability and sustained-release. Here,
      we synthesized a pH-sensitive material, N-(3-Aminopropyl)imidazole-cholesterol
      (IM-Chol) and prepared a novel pH-sensitive liposomes using IM-Chol and
      phosphatidylcholine. IM-Chol was synthesized through amidation reaction between
      the amino group of N-(3-Aminopropyl)imidazole and acyl chloride group of
      cholesteryl chloroformate in a weak base solution. Optimal conditions to prepare
      liposomes were obtained by the orthogonal experiment with the higher
      encapsulation efficiency as the evaluation indicator. The properties of
      liposomes, such as particle size, zeta potential, morphology, encapsulation
      efficiency, drug release behavior and in vitro cell toxicity were evaluated by
      transmission electron microscopy (TEM), dynamic light scattering (DLS) and MTT
      assay respectively. The results showed that the average particle size of IM-Chol
      liposomes was 141nm (PDI 0.323). Liposomes can assemble into uniform spheres at
      pH 7.4, but under the condition of pH 5.0, the spherical structure of IM-Chol
      liposomes was broken, exhibiting pH-sensitive property. In vitro drug releasing
      studies demonstrated the controlled-release behavior of the curcumin (CUR) in the
      IM-Chol liposomes. The cumulative release of CUR reached to 72.5% in the first
      24h at pH 5.0, faster than that at pH 7.4, which confirmed that the drug carrier
      displayed pH-sensitive release behaviors. In addition, the MTT assay was employed
      to test the cytotoxicity of IM-Chol liposomes and CUR IM-Chol liposomes. All cell
      viabilities were greater than 80% after incubating for 24h, even up to the
      highest dose of 500mg/L, indicating that IM-Chol liposomes had good
      biocompatibility. The tumor inhibitory results towards EC109 cells of free CUR
      and CUR-loaded IM-Chol liposomes indicated that IM-Chol liposomes indeed enhanced
      the cell killing effect of CUR. These results showed that the novel IM-Chol
      liposomes prepared in this paper had pH-sensitive property and were expected to
      play a huge potential in tumor treatment.

PMID- 27889589
TI  - Higher morale is associated with lower risk of depressive disorders five years
      later among very old people.
AB  - OBJECTIVE: The aim of this study was to investigate whether higher morale, i.e.
      future-oriented optimism, at baseline was associated with lower risk of
      depressive disorders five years later among very old people.Methods The
      Umea85+/GErontological Regional Database, a population-based study with a
      longitudinal design, recruited participants in Sweden and Finland aged 85, 90 and
      >=95 years. The sample in the present study included 647 individuals (89.1+/-4.4
      years (Mean+/-SD), range 85-103). After five years, 216 were alive and agreed to
      a follow-up (92.6+/-3.4 years, range 90-104). The Philadelphia Geriatric Center
      Morale Scale (PGCMS) was used to assess morale. The depressive disorder diagnosis
      was determined according to DSM-IV based on medical records and interview data
      including assessment scales for depressive disorders. A number of
      sociodemographic, functional and health-related variables were analysed as
      possible confounders.Results For those with no depressive disorders at baseline,
      the only baseline variable significantly associated with depressive disorders
      five years later was the PGCMS score. A logistic regression model showed lower
      risk of depressive disorders five years later with higher baseline PGCMS scores
      (odds ratio 0.779 for one point increase in PGCMS, p<0.001). The association
      remained after adjusting for social isolation (p<0.1 association with depressive
      disorders five years later).Conclusion Our results indicate that the higher the
      morale, the lower the risk of depressive disorders five years later among very
      old people. The PGCMS seems to identify those very old individuals at increased
      risk of depressive disorders five years later. Preventive measures could
      befocused on this group.

PMID- 27889590
TI  - Perceived and objective entrance-related environmental barriers and daily out-of
      home mobility in community-dwelling older people.
AB  - PURPOSE: We studied whether entrance-related environmental barriers, perceived
      and objectively recorded, were associated with moving out-of-home daily in older
      people with and without limitations in lower extremity performance. METHODS:
      Cross-sectional analyses of the "Life-space mobility in old age" cohort including
      848 community-dwelling 75-90-year-old of central Finland. Participants reported
      their frequency of moving out-of-home (daily vs. 0-6 times/week) and perceived
      entrance-related environmental barriers (yes/no). Lower extremity performance was
      assessed (Short Physical Performance Battery) and categorized as poorer (score 0
      9) or good (score 10-12). Environmental barriers at entrances and in exterior
      surroundings were objectively registered (Housing Enabler screening tool) and
      divided into tertiles. Logistic regression analyses were adjusted for age, sex,
      number of chronic diseases, cognitive function, month of assessment, type of
      neighborhood, and years lived in the current home. RESULTS: At home entrances a
      median of 6 and in the exterior surroundings 5 environmental barriers were
      objectively recorded, and 20% of the participants perceived entrance-related
      barriers. The odds for moving out-of-home less than daily increased when
      participants perceived entrance-related barrier(s) or when they lived in homes
      with higher numbers of objectively recorded environmental barriers at entrances.
      Participants with limitations in lower extremity performance were more
      susceptible to these environmental barriers. Objectively recorded environmental
      barriers in the exterior surroundings did not compromise out-of-home mobility.
      CONCLUSION: Entrance-related environmental barriers may hinder community-dwelling
      older people to move out-of-home daily especially when their functional capacity
      is compromised. Potentially, reducing entrance-related barriers may help to
      prevent confinement to the home.

PMID- 27889591
TI  - Adverse events and treatment discontinuations of antimuscarinics for the
      treatment of overactive bladder in older adults: A systematic review and meta
      analysis.
AB  - INTRODUCTION: Antimuscarinics should be used with caution in older adults with
      overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic
      reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have
      not specified risk in the elderly, the population at highest risk for AEs. The
      aim of this review is to explore and evaluate AEs and treatment discontinuations
      in adults 65 or older taking antimuscarinics for OAB. METHODS: Keywords were
      searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled
      Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled
      analyses that compared antimuscarinics to placebo or another antimuscarinic were
      performed in February 2015. Studies assessing AEs or treatment discontinuations
      in a population of adults 65 or older were included. The Jadad Criteria and
      McHarm Tool were used to assess the quality of the trials. RESULTS: A total of 16
      studies met the inclusion criteria. Eighty AEs and 27 reasons for treatment
      discontinuation were described in the included studies and further explored.
      Anticholinergic AEs were more common in antimuscarinics compared to placebo.
      Incidence of dizziness, dyspepsia, and urinary retention with fesoterodine,
      headache with darifenacin, and urinary tract infections with solifenacin were
      significantly higher compared to placebo. Treatment discontinuation due to AEs
      and dry mouth were higher in the antimuscarinics when compared to placebo in
      older adults. CONCLUSIONS: Treatment for overactive bladder using antimuscarinics
      in adults aged 65 or older resulted in significant increases in risk for several
      AEs compared to placebo including anticholinergic and non-anticholinergic AEs.

PMID- 27889592
TI  - Marijuana effects on changes in brain structure and cognitive function among HIV+
      and HIV- adults.
AB  - BACKGROUND: The current study examined the independent and interactive effects of
      HIV and marijuana (MJ) use on brain structure and cognitive function among a
      sample of HIV-positive (HIV+) and HIV-negative (HIV-) individuals. METHODS:
      Participants (HIV+, n=48; HIV-, n=29) individuals underwent cognitive testing,
      questionnaires about substance use, and brain MRI. The HIV+ group was clinically
      stable based upon current plasma CD4 count, 50% had undetectable viral load
      (i.e.,<20 copies/mL), and all were on a stable regimen of cART. RESULTS: For HIV+
      and HIV- participants, higher levels of MJ use were associated with smaller
      volumes in the entorhinal cortex and fusiform gyrus. HIV status (but not MJ use)
      was associated with cingulate thickness, such that HIV+ participants evidenced
      smaller thickness of the cingulate, as compared to HIV- controls. Regarding
      neurocognitive functioning, there was a HIV*MJ interactive effect on global
      cognition, such that when the amount of MJ use was less than 1.43g per week, the
      HIV- group displayed significantly better neurocognitive performance than the
      HIV+ group (t=3.14, p=0.002). However, when MJ use reached 1.43g per week, there
      were no significant HIV group differences in global cognitive performance
      (t=1.39, p=0.168). CONCLUSIONS: Our results show independent and interactive
      effects of HIV and MJ on brain structure and cognition. However, our results do
      not support that HIV+ MJ users are at greater risk for adverse brain or cognitive
      outcomes compared to HIV- MJ users.

PMID- 27889593
TI  - Prevalence and patterns of cigarette smoking among patients co-infected with
      human immunodeficiency virus and tuberculosis in Tanzania.
AB  - INTRODUCTION: Cigarette smoking is one of the major risk factors for non-AIDS
      related morbidities and is highly prevalent among HIV infected people. However,
      no reports exist from Tanzania, one of the countries highly affected by the HIV
      pandemic and one of Africa's biggest tobacco producer. METHODS: We examined the
      patterns and prevalence of cigarette smoking among HIV and TB co-infected adult
      patients in Dar es Salaam using a cross sectional study design. Proportions were
      used to describe the pattern of cigarette smoking. Logistic regression was used
      to assess the association of various participant characteristics with smoking.
      RESULTS: Out of the 518 participants, 17 (3.3%) were current smokers, 96 (18.5%)
      were ex-smokers and the rest (78.2%) denied ever smoking. Male sex (p<0.001),
      alcohol (p<0.001), and illicit substance use (p<0.001) were significantly
      associated with cigarette smoking. CONCLUSIONS: The study indicates that, the
      level of current cigarette smoking among HIV/TB co-infected patients in Dar es
      Salaam is low. Nevertheless, the preponderance of cigarette smoking among men,
      alcohol drinkers, and those who use illicit substances provides a unique
      opportunity for targeting such population with smoking cessation interventions;
      HIV care and treatment clinics are uniquely positioned to provide such
      interventions.

PMID- 27889594
TI  - Racial/ethnic differences in 30-year trajectories of heavy drinking in a
      nationally representative U.S. sample.
AB  - BACKGROUND: Racial/ethnic minorities bear a disproportionate burden of alcohol
      related problems in the U.S. It is unknown whether this reflects harmful patterns
      of lifecourse heavy drinking. Prior research shows little support for the latter
      but has been limited to young samples. We examine racial/ethnic differences in
      heavy drinking trajectories from ages 21 to 51. METHODS: Data on heavy drinking
      (6+ drinks/occasion) are from the 1979 National Longitudinal Survey of Youth
      (N=9468), collected between 1982 and 2012. Sex-stratified, generalized estimating
      equations (GEE) were used to model heavy drinking frequency trajectories as a
      function of age with a cubic curve, and interactions of race with age terms were
      tested to assess racial/ethnic differences. Models adjusted for time-varying
      socioeconomic status and marital and parenting status; predictors of trajectories
      were examined in race- and sex-specific models. RESULTS: White men and women had
      similarly steep declines in heavy drinking frequency throughout the 20s,
      contrasting with slower declines (and lower peaks) in Black and Hispanic men and
      women. During the 30s there was a Hispanic-White crossover in men's heavy
      drinking curves, and a Black-White female crossover among lifetime heavy
      drinkers; by age 51, racial/ethnic group trajectories converged in both sexes.
      Greater education was protective for all groups. CONCLUSION: Observed
      racial/ethnic crossovers in heavy drinking frequency following young adulthood
      might contribute to disparities in alcohol-related problems in middle adulthood,
      and suggest a need for targeted interventions during this period. Additionally,
      interventions that increase educational attainment may constitute an important
      strategy for reducing heavy drinking in all groups.

PMID- 27889595
TI  - Is there a role for salvage radiotherapy in locally advanced breast cancer
      refractory to neoadjuvant chemotherapy?
AB  - INTRODUCTION: Locally advanced breast cancer (LABC) is a major problem,
      especially in developing countries. The standard treatment for LABC is
      neoadjuvant chemotherapy, with or without anti-Her2 therapy, followed by surgery,
      radiotherapy, and adjuvant systemic treatment if appropriate. However, there are
      few data in the literature addressing alternatives when neoadjuvant chemotherapy
      fails to reduce the tumour for surgery. MATERIALS AND METHODS: We conducted a
      retrospective study including all patients who had non-metastatic LABC treated
      with neoadjuvant chemotherapy and who were not eligible for surgical resection;
      these patients were submitted to salvage radiotherapy (RTX) between January 2000
      and December 2012 at the Brazilian National Cancer Institute. RESULTS: Fifty
      seven patients were included, with a median age of 51 (23-72) years. The most
      frequent clinical stages were IIIA and IIIB, corresponding to 19.3% and 70.2%,
      respectively; mean tumour size was 8.74 (3-18) cm, and 44 patients (77.2%) had
      nodal involvement. Chemotherapeutic regimens containing anthracyclines were
      prescribed to 98.2% of the patients. Fifteen patients (26.3%) received taxanes
      and anthracyclines. Radiation dose was 50 Gy divided into 25 fractions; 43
      patients (75.4%) had their tumours downsized by RTX and underwent mastectomy.
      Overall survival (OS) was 38 (23-52) months. Patients who were submitted to
      surgery had an OS of 49 (28-70) months and those who were not eligible for
      mastectomy after radiotherapy had an OS of 18 (9-27) months. CONCLUSION: This
      retrospective study confirms that RTX is an effective treatment to downsize LABC
      tumours with low or no response to chemotherapy, thereby enabling surgical
      resection which may improve overall patient outcome.

PMID- 27889596
TI  - Using ultrasound and palpation for predicting axillary lymph node status
      following neoadjuvant chemotherapy - Results from the multi-center SENTINA trial.
AB  - BACKGROUND: With the growing importance of neoadjuvant systemic therapy (NST) the
      assessment of post neoadjuvant axillary status is of increasing importance
      especially in patients who presented initially with suspicious nodes (cN1). This
      study aims to investigate the predictive value of palpation and axillary
      ultrasound of formerly cN1 patients following NST. PATIENTS AND METHODS: The
      SENTINA trial (SENTinel NeoAdjuvant) is a 4-arm prospective multicenter study
      designed to evaluate the role of sentinel node biopsy (SLNB) in the context of
      neoadjuvant systemic treatment (NST) of breast cancer patients. RESULTS: 1240
      patients from 103 institutions entered the trial. 715 (arm C n = 592; arm D n =
      123) patients, who presented initially cN1 underwent clinical evaluation of lymph
      node status following NST. Palpation alone demonstrated a sensitivity of 8.3%,
      specifity of 94.8% and a negative predictive value (NPV) of 46.6%. Ultrasound
      alone revealed a sensitivity of 23.9%, specificity 91.7%, and a NPV of 50.3%.The
      investigators combined classification (palpation and ultrasound) resulted in a
      sensitivity of 24.4%, specificity 91.4%, and a NPV of 50.3%. Investigators
      classified the axilla nodes as being unsuspicious (cN0) following NST in 592/715
      patients; of them 298 (50.3%) were pN0, 151 (25.5%) had 1-2 histologically
      involved nodes and 143 (24.2%) had >2 histologically involved nodes. CONCLUSION:
      The diagnostic accuracy of ultrasound and palpation following NST is unacceptably
      low and additional tools for evaluation of the axillary lymph node status
      following NST are urgently needed.

PMID- 27889597
TI  - Is there any association between Toxoplasma gondii infection and bipolar
      disorder? A systematic review and meta-analysis.
AB  - BACKGROUND: The relationship between Toxoplasma gondii infection and the
      development of bipolar disorder (BD) has long been investigated, yet to date it
      is still poorly understood and documented. The aim of this review is to derive a
      summary estimate of the strength of the association between infection with T.
      gondii and BD from the available published studies. METHODS: A systematic review
      was performed using PubMed, LILACS, PsycINFO, and Embase databases. Studies which
      included a proportion of seropositive BD patients and controls were further
      examined in a meta-analysis. RESULTS: One hundred eighteen citations were
      initially retrieved. Thirteen studies were included in our systematic review.
      Eight out of these thirteen studies were included in our meta-analysis.
      Statistical analyses showed that T. gondii infection is associated with with BD
      (OR=1.26). LIMITATIONS: Small sample size was the major limitation among the
      studies that carried out serological analyses. In addition, the available studies
      did not have enough information on disease status/severity or type of bipolar
      disorder. Also, it was not possible to analyze pregnancy status or perinatal
      infection. Future studies addressing the aforementioned topics are clearly
      needed. CONCLUSIONS: Despite heterogeneous results, patients with BD are more
      likely to be infected by T. gondii than controls. Early T. gondii infection might
      predispose the development of BD. T.gondii infection is becoming clinically
      relevant in psychiatric disorders and future mechanistic studies are required to
      elucidate the underlying pathophysiological mechanisms.

PMID- 27889598
TI  - Association between antipsychotic drug use and cataracts in patients with bipolar
      disorder: A population-based, nested case-control study.
AB  - BACKGROUND: No previous study has focused on the association between use of
      antipsychotic drugs and the development of cataracts in patients with bipolar
      disorder (BD); hence, we aimed to examine this association in the present study.
      METHODS: We conducted a retrospective nested case-control study using data from
      the National Health Insurance Database of Taiwan between 2000 and 2011. A total
      of 3292 BD patients, 1684 with cataracts and 1608 controls matched for age, sex,
      and index date, were included. Antipsychotic drug exposure was categorized by
      type of drug and duration of use. A conditional logistic regression analysis was
      used to analyze the association. RESULTS: Among BD patients, we found
      significantly reduced odds ratio (OR) of cataract development among past
      (adjusted OR (AOR), 0.74; 95% confidence interval (CI), 0.62-0.89; p=0.001) and
      continuous users (AOR, 0.71; 95% CI, 0.59-0.85; p<0.001) of atypical
      antipsychotics. No association was found between the odds of cataract development
      and typical antipsychotics. Besides, concomitant use of antidepressants (AOR,
      1.23; 95% CI, 1.06-1.43; p=0.007) and mood stabilizers (AOR, 1.23; 95% CI, 1.06
      1.42; p=0.007) were associated with increased odds of cataract development.
      LIMITATIONS: Some important contributors to cataract development such as family
      history of cataract, smoking and alcohol exposure could not be measured from the
      claims data and this may confound the results. CONCLUSIONS: Reduced odds of
      cataract were found in patients with BD taking atypical antipsychotics. However,
      given that BD patients often have risk factors for developing cataract, regular
      ocular evaluations are recommended for those treated with antipsychotics drugs.

PMID- 27889599
TI  - Patatin-like phospholipase domain-containing protein 3 (PNPLA3): A potential role
      in the association between liver disease and bipolar disorder.
AB  - OBJECTIVE: Due to the increased prevalence of liver disease in patients with
      bipolar disorder, we examined the potential role of the patatin-like
      phospholipase domain-containing protein 3 (PNPLA3) variant among individuals with
      bipolar disorder and those with no mood disorder. METHODS: We used the National
      Health and Nutrition Examination Survey (NHANES) database (aged 15-39 years) to
      identify a group of individuals with a bipolar diagnosis and a control group of
      individuals with no mood disorder. A total of 1931 individuals were randomly
      selected, one from each family containing information on the PNPLA3 genotype to
      be used in the analysis. RESULTS: Analyses revealed individuals with the
      recessive variant genotype (MM) had an adjusted odds ratio for bipolar disorder
      of about 4.6 compared to individuals with either IM or II genotypes of the PNPLA3
      variant. LIMITATIONS AND CONCLUSIONS: Limitations of this study include the use
      of a lay-administered survey in for diagnosis of bipolar disorder in NHANES. The
      association between the PNPLA3 variant and bipolar disorder may help guide
      further work on medication effectiveness, treatment options, prevention
      approaches, and understanding potential medication side effects among specific
      subgroups of individuals with the MM genotype.

PMID- 27889600
TI  - Comparative proteomic analysis of female and male venoms from the Mexican
      scorpion Centruroides limpidus: Novel components found.
AB  - Venom from male and female scorpions of the species Centruroides limpidus were
      separated by HPLC and their molecular masses determined by mass spectrometry. The
      relative concentration of components eluting in equivalent retention times from
      the HPLC column shows some differences. A new peptide with 29 amino acids, cross
      linked by three disulfide bonds was found in male scorpions and its structure
      determined. Another unknown peptide present in female venom, with sequence
      identity similar to K+-channel blocking peptide was isolated. This peptide
      contains 39 amino acid residues linked by three disulfide bonds. Due to sequence
      similarities, a systematic number (alphaKTx2.18) was assigned. Venom from male
      and female scorpions was separated by Sephadex G-50 gel filtration. Components of
      fraction I of this chromatogram were analyzed by two-dimensional gel
      electrophoresis and 41 spots were selected (20 from female and 21 from male). The
      spots were excised from the gel, enzymatically digested and sequenced by LC
      MS/MS. This procedure allowed the identification of several proteins containing
      similar amino acid sequence of other known proteins registered on UniProt
      database. Among these proteins the presence of metalloproteinases (proteolytic
      enzymes), hyaluronidases and phosphatases were experimentally determined and
      shown to be present in both venom samples. The results shown here should help
      further work aimed at fully identification of the structure and function of venom
      components form C. limpidus male and female scorpions.

PMID- 27889602
TI  - Toxicity evaluation and initial characterization of the venom of a Colombian
      Latrodectus sp.
AB  - The genus Latrodectus has not been studied in Colombia even though it is
      medically important worldwide; there are three species for the country, this
      study focused on a non-identified species found in the Tatacoa Desert in the
      Huila Department. This research is the first approximation to the extraction,
      composition analysis and toxicity evaluation of the venom of a species of the
      genus Latrodectus in Colombia; and aims to evaluate the toxicity by the initial
      characterization of its venom. The venom extraction was accomplished with
      electrostimulation and total protein concentration was determined by the Lowry
      method and BCA assays from crude venom; with these methods, high protein
      concentration of the samples was measured. Bioassays on mice were also made to
      evaluate the toxicity and compare the symptoms produced by this Colombian spider
      to the Latrodectism Syndrome. Finally, an SDS-PAGE electrophoresis was used to
      separate the main components of high molecular weight from the samples and
      compared to a control of the venom of Latrodectus mactans to determine if the
      venom composition is different between these two species.

PMID- 27889601
TI  - Microcystin-LR induced liver injury in mice and in primary human hepatocytes is
      caused by oncotic necrosis.
AB  - Microcystins are a group of toxins produced by freshwater cyanobacteria. Uptake
      of microcystin-leucine arginine (MC-LR) by organic anion transporting polypeptide
      1B2 in hepatocytes results in inhibition of protein phosphatase 1A and 2A, and
      subsequent cell death. Studies performed in primary rat hepatocytes demonstrate
      prototypical apoptosis after MC-LR exposure; however, no study has directly
      tested whether apoptosis is critically involved in vivo in the mouse, or in human
      hepatocytes. MC-LR (120 MUg/kg) was administered to C57BL/6J mice and cell death
      was evaluated by alanine aminotransferase (ALT) release, caspase-3 activity in
      the liver, and histology. Mice exposed to MC-LR had increases in plasma ALT
      values, and hemorrhage in the liver, but no increase in capase-3 activity in the
      liver. Pre-treatment with the pan-caspase inhibitor z-VAD-fmk failed to protect
      against cell death measured by ALT, glutathione depletion, or hemorrhage.
      Administration of MC-LR to primary human hepatocytes resulted in significant
      toxicity at concentrations between 5 nM and 1 MUM. There were no elevated caspase
      3 activities and pretreatment with z-VAD-fmk failed to protect against cell death
      in human hepatocytes. MC-LR treated human hepatocytes stained positive for
      propidium iodide, indicating membrane instability, a marker of necrosis. Of note,
      both increases in PI positive cells, and increases in lactate dehydrogenase
      release, occurred before the onset of complete actin filament collapse. In
      conclusion, apoptosis does not contribute to MC-LR-induced cell death in the in
      vivo mouse model or in primary human hepatocytes in vitro. Thus, targeting
      necrotic cell death mechanisms will be critical for preventing microcystin
      induced liver injury.

PMID- 27889603
TI  - Two symbiotic bacteria of the entomopathogenic nematode Heterorhabditis spp.
      against Galleria mellonella.
AB  - The entomopathogenic nematode Heterorhabditis spp. is considered a promising
      agent in the biocontrol of injurious insects of agriculture. However, different
      symbiotic bacteria associated with the nematode usually have different
      specificity and virulence toward their own host. In this study, two symbiotic
      bacteria, LY2W and NK, were isolated from the intestinal canals of two
      entomopathogenic nematode Heterorhabditis megidis 90 (PDSj1 and PDSj2) from
      Galleria mellonela, separately. To determine their species classification, we
      carried out some investigations on morphology, culture, biochemistry, especially
      16S rDNA sequence analyses. As a result, both of them belong to Enterobacter
      spp., showing the closest relatedness with Enterobacter gergoviae (LY2W) and
      Enterobacter cloacae (NK), respectively. Moreover, the toxicity to Galleria
      mellonella was examined using both the metabolites and washed cells (primary and
      secondary) of these two strains. The results indicated both metabolites and cells
      of the primary-type bacteria could cause high mortalities (up to 97%) to Galleria
      mellonella, while those of the primary-type bacteria only killed 20%. These
      findings would provide new symbiotic bacteria and further references for
      biological control of the agricultural pest.

PMID- 27889604
TI  - Suicidal ideation, plans and attempts among medical college students in china:
      The effect of their parental characteristics.
AB  - Medical college students are a high-risk population of suicidal ideation, plan
      and attempt. However, few studies discuss the effect of parental characteristics
      on suicidal ideation, plans and attempts among medical college students in China.
      A total of 2198 respondents answered the questionnaires referring social
      demographic characteristics, psychological conditions, parental characteristics,
      suicidal ideation, plan and attempt. The prevalence of suicidal ideation, plan
      and attempt among the subjects were 17.9%, 5.2% and 4.3%, respectively. The
      results of multiple logistic regression showed that male, mother's education
      level, mother's parenting style, relationship in parents and psychological
      condition were associated with lifetime suicidal ideation. Male, mother's
      vocation, mother's parenting style, relationship in parents and psychological
      conditions were associated with suicide plan. Male, relationship in parents and
      psychological condition were associated with suicide attempt. Those imply that
      mother may play more roles on suicidal ideation and plan than father among
      medical college students in China. Psychological condition has a very strong
      association with suicidal ideation, plan and attempt.

PMID- 27889605
TI  - Posterior composites: Update on cavities and filling techniques.
AB  - OBJECTIVES: The aim of this paper is to examine cavity design for posterior resin
      composite restorations and to discuss various resin composite filling techniques.
      DATA: Literature with regard to cavity preparation for amalgam and resin
      composite restorations has been reviewed. An overview of available bulkfill resin
      composite systems is provided and a categorization of these systems according to
      their clinical application and their intended use is outlined. SOURCES: A
      literature search was carried out by the authors in Medline. STUDY SELECTION: Pre
      defined inclusion criteria based on keywords were included and reviewed.
      CONCLUSIONS: Minimum cavity preparations are advised for posterior resin
      composite restorations, preserving the greatest amount of healthy tooth
      structure. For resin composite restorations only the lesion of caries needs to be
      removed with all remaining tooth structure protected for the bonding process. The
      anticipated outcome of this philosophy will result in increased survival of
      teeth. Newer bulkfill restorative resins offer many advantages such as reduces
      time for placement.

PMID- 27889606
TI  - Re-interventions after restoring teeth-Mining an insurance database.
AB  - OBJECTIVES: The aim of this study was to examine re-interventions after
      restorative treatment. METHODS: The data was collected from the digital database
      of a major German national health insurance company. Only permanent teeth were
      observed. Placing a permanent restoration other than a crown regardless of
      involved surfaces and material was the study intervention. The data did not allow
      for a differentiation between fillings and inlays that were estimated only a very
      small portion of the restorations. Success was defined as not undergoing any
      restorative re-intervention with fillings or inlays on the same tooth (primary
      outcome) and assessed with Kaplan-Meier survival analyses over four years. An
      additional analysis was conducted rating "crowning" and "extraction" of
      respective teeth as target events. Differences were tested with the Log-Rank
      test. A multivariate Cox regression analyses was carried out. RESULTS: A total of
      17,024,344 restorations placed in 4,825,408 anterior teeth and 9,973,177
      posterior teeth could be traced. Focussing on the primary outcome re
      intervention, the cumulative four-year success rate was 69.9% for one surface
      restorations, 74.8% for two surface restorations, 66.6% for three surface
      restorations and 61.0% for four surface and more extended restorations. These
      differences were significant (p<0.0001). Focussing on all three target events re
      intervention, crowning and extraction, the cumulative four-year success rate was
      66.1% for one surface restorations, 67.5% for two surface restorations, 63.0% for
      three surface restorations and 55.8% for four surface and more extended
      restorations. The number of restoration surfaces as well as the tooth position
      remained significant in the multivariate Cox regression. CONCLUSIONS: The
      sustainability of restorative dental treatment under the terms and conditions of
      the German national health insurance system shows room for improvement. From a
      public health perspective, special focus should be laid on primary and secondary
      prevention to minimize the restorative treatment need. CLINICAL SIGNIFICANCE
      STATEMENT: This study shows that re-interventions are observed regularly after
      restorative treatment. Therefore, preventive and restorative strategies should be
      revisited and optimised.

PMID- 27889607
TI  - Leptin/OB-R signaling is elevated in mice with Sjogren's syndrome and is
      implicated in disease pathogenesis.
AB  - Sjogren's syndrome (SjS) is a systemic autoimmune disease resulting in a severe
      dry mouth and dry eyes. Currently, care for patients with SjS is palliative, as
      no established therapeutics target the disease directly, and its pathogenetic
      mechanisms are uncertain. Leptin activates B cells to induce the secretion of
      proinflammatory and anti-inflammatory cytokines and is elevated in several
      autoimmune diseases. In this study, we found the expression of leptin and its
      receptor OB-R in mouse models of SjS are elevated both locally and systemically
      during SjS progression. Recombinant serotype 2 adeno-associated viral (rAAV2)
      vectors expressing either OB-R shRNA (rAAV2-shOB-R) or none (rAAV2-null) were
      injected into 4 or 16 week-old BALB/c NOD/LtJ (NOD) mice and resulted in a modest
      reduction in glandular inflammation in the SjS model. In conclusion, Leptin/OB-R
      signaling may be pathogenically involved in SjS and may serve as a new marker and
      a potential therapeutic target.

PMID- 27889608
TI  - SPOCK1 is up-regulated and promotes tumor growth via the PI3K/AKT signaling
      pathway in colorectal cancer.
AB  - SPOCK1 encodes a Ca2+-binding matricellular glycoprotein which plays an oncogenic
      role in cancer cells. However, the role of SPOCK1 in the pathogenesis of
      colorectal cancer (CRC) has not been determined. Here, SPOCK1 was found higher
      expressed in CRC tissues than that of adjacent normal tissues. Furthermore, up
      regulated expression of SPOCK1 in CRC patients was associated with tumor size and
      TNM stage. In addition, we observed that the depletion of SPOCK1 inhibited
      proliferation in vitro and tumorigenicity in vivo and promoted apoptosis in cell
      culture. Our data suggest that inactivation of PI3K/Akt signaling pathway was
      involved in down-regulation of SPOCK1-mediated suppression of tumor cell
      proliferation. These results suggest that SPOCK1 expression is correlated with
      malignant features of CRC and may serve as potential therapeutic and preventive
      strategies for CRC.

PMID- 27889609
TI  - Aquaporin-2 Ser-261 phosphorylation is regulated in combination with Ser-256 and
      Ser-269 phosphorylation.
AB  - Aquaporin-2 (AQP2) is a water channel in collecting duct principal cells in the
      kidney. Vasopressin catalyzes AQP2 phosphorylation at several serine sites in its
      C-terminus: Ser-256, Ser-261, and Ser-269. Upon stimulation by vasopressin, Ser
      269 phosphorylation increases and Ser-261 phosphorylation decreases. Ser-256
      phosphorylation is relatively constant. However, whether these types of phospho
      regulation occur independently in distinct AQP2 populations or sequentially in
      the same AQP2 population is unclear. Especially, the manner of vasopressin
      mediated Ser-261 phospho-regulation has been in controversy. In this study, we
      established phospho-specific AQP2 immunoprecipitation assays and investigated how
      pS256-positive AQP2 and pS269-positive AQP2 are catalyzed by forskolin or
      vasopressin, focusing on their Ser-261 phosphorylation status in polarized Madin
      Darby canine kidney (MDCK) cells and in mice. In forskolin-treated MDCK cells,
      Ser-269 phosphorylation preceded Ser-261 dephosphorylation and Ser-256
      phosphorylation was constant. In both MDCK cells and mouse kidney, phospho
      specific immunoprecipitation revealed that the regulated Ser-269 phosphorylation
      occurred in the pS256-positive AQP2 population. Importantly, basal-state Ser-261
      phosphorylation and its regulated dephosphorylation occurred in the pS256- and
      pS269-positive AQP2 population. These results provide the direct evidence that
      the Ser-261 dephosphorylation is involved in the pS256- and pS269-related AQP2
      regulation.

PMID- 27889610
TI  - CACUL1/CAC1 attenuates p53 activity through PML post-translational modification.
AB  - Promyelocytic leukaemia (PML) is a tumor suppressor protein covalently conjugated
      with SUMO family proteins, leading to the formation of PML nuclear bodies (NBs).
      PML-NBs provide a platform for efficient posttranslational modification of
      targets and protein-protein interaction, contributing to the adjustment of gene
      expression and chromatin integrity. Although PML SUMOylation is thought to play
      important roles in diverse cellular functions, the control mechanisms of adequate
      modification levels have remained unsolved. Here, we report that Cullin-related
      protein CACUL1/CAC1 (CACUL1) inhibits PML posttranslational modification. CACUL1
      interacts with PML and suppresses PML SUMOylation, leading to the regulation of
      PML-NB size in the nucleus. We also found that Ubc9, a SUMO-conjugating enzyme,
      binds to CACUL1 and antagonizes the interaction between CACUL1 and PML.
      Furthermore, CACUL1 attenuates p53 transcriptional activity. These data suggest
      that CACUL1 is a novel regulator that negatively controls p53 activity through
      the regulation of PML SUMOylation.

PMID- 27889611
TI  - Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of
      Wilms' tumor gene 1 (WT1) protein in leukemic cells.
AB  - Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been
      implicated as an oncogene in leukemia and several other malignancies. When
      investigating possible gene expression network partners of WT1 in a large acute
      myeloid leukemia (AML) patient cohort, one of the genes with the highest
      correlation to WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme
      in the de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To
      investigate the possible relationship between WT1 and QPRT, we overexpressed WT1
      in hematopoietic progenitor cells and cell lines, resulting in an increase of
      QPRT expression. WT1 knock-down gave a corresponding decrease in QPRT gene and
      protein expression. Chromatin-immunoprecipitation revealed WT1 binding to a
      conserved site in the first intron of the QPRT gene. Upon overexpression in
      leukemic K562 cells, QPRT conferred partial resistance to the anti-leukemic drug
      imatinib, indicating possible anti-apoptotic functions, consistent with previous
      reports on glioma cells. Interestingly, the rescue effect of QPRT overexpression
      was not correlated to increased NAD + levels, suggesting NAD + independent
      mechanisms. We conclude that QPRT, encoding a protein with anti-apoptotic
      properties, is a novel and direct target gene of WT1 in leukemic cells.

PMID- 27889612
TI  - TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell
      proliferation.
AB  - Large amount of clinical evidence has demonstrated that insulin resistance is
      closely related to oncogenesis of endometrial cancer (EC). Despite recent studies
      showed the up-regulatory role of insulin in G protein-coupled estrogen receptor
      (GPER/GPR30) expression, GPER expression was not decreased compared to control
      when insulin receptor was blocked even in insulin treatment. The purpose of this
      study was to explore the possible mechanism by which insulin up-regulates GPER
      that drives EC cell proliferation. For this purpose, we first investigated the
      GPER expression in tissues of endometrial lesions, further explored the effect of
      GPER on EC cell proliferation in insulin resistance context. Then we analyzed the
      role of Ten-Eleven Translocation 1 (TET1) in insulin-induced GEPR expression and
      EC cell proliferation. The results showed that GPER was highly expressed in
      endometrial atypical hyperplasia and EC tissues. Mechanistically, insulin up
      regulated TET1 expression and the latter played an important role in up
      regulating GPER expression and activating PI3K/AKT signaling pathway. TET1
      mediated GPER up-regulation was another mechanism that insulin promotes EC cell
      proliferation.

PMID- 27889613
TI  - Two approaches, one problem: Cultural constructions of type II diabetes in an
      indigenous community in Yucatan, Mexico.
AB  - The emerging epidemic of obesity and type II diabetes in Mexico has recently
      propelled the nation into the public health spotlight. In the state of Yucatan,
      the experience of diabetes is greatly impacted by two cultural constructions of
      disease. In this setting, elements of Yucatec Mayan health practices as well as
      the biomedical model affect the approach to type II diabetes. Both frameworks
      offer unique understandings of the etiology of diabetes and recommend different
      ways to manage the condition. Based on in-depth and semi-structured interviews
      with both community members and clinicians, the present study seeks to understand
      how diabetes is understood and treated in indigenous settings in rural Yucatan.
      We explore the context in which community members navigate between locally
      available healthcare options, choose one over the other, or incorporate
      strategies from both into their diabetes care regimens. The tension between
      indigenous community members and their biomedical healthcare providers, the
      changing food environment of this community, and the persistence of traditional
      gender constructions affect the management of type II diabetes and its associated
      symptoms.

PMID- 27889614
TI  - Competitive replication kinetics and pathogenicity in pigs co-infected with
      historical and newly invading classical swine fever viruses.
AB  - Classical swine fever (CSF), an economically important and highly contagious
      disease of pigs, is caused by classical swine fever virus (CSFV). In Taiwan,
      CSFVs from field outbreaks belong to two distinct genotypes. The historical
      genotype 3.4 dominated from the 1920s to 1996, and since 1996, the newly invading
      genotype 2.1 has dominated. To explain the phenomenon of this virus shift in the
      field, representative viruses belonging to genotypes 2.1 and 3.4 were either
      inoculated alone (single infection) or co-inoculated (co-infection), both in vivo
      and in vitro, to compare the virus replication and pathogenesis. In pigs co
      infected with the genotype 2.1 TD/96/TWN strain and the genotype 3.4
      94.4/IL/94/TWN strain, the newly invading genotype 2.1 was detected earlier in
      the blood, oral fluid, and feces, and the viral loads were consistently and
      significantly higher than that of the historical genotype 3.4. In cell cultures,
      the ratio of secreted virus to cell-associated virus of the genotype 2.1 strain
      was higher than that of the genotype 3.4 strain. This study is the first to
      demonstrate a possible explanation of virus shift in the field, wherein the newly
      invading genotype 2.1 replicates more efficiently than did genotype 3.4 and
      outcompetes the replication and pathogenicity of genotype 3.4 in pigs in the
      field.

PMID- 27889615
TI  - Inactivation of Zika virus in human breast milk by prolonged storage or
      pasteurization.
AB  - Zika virus infection during pregnancy poses a serious risk for pregnant women as
      it can cause severe birth defects. Even though the virus is mainly transmitted
      via mosquitos, human-to-human transmission has been described. Infectious viral
      particles have been detected in breast milk of infected women which raised
      concerns regarding the safety of breastfeeding in areas of Zika virus
      transmission or in case of a suspected or confirmed Zika virus infection. In this
      study, we show that Zika virus is effectively inactivated in human breast milk
      after prolonged storage or upon pasteurization of milk.

PMID- 27889617
TI  - Aquatic viral metagenomics: Lights and shadows.
AB  - Viruses are the most abundant biological entities on Earth, exceeding bacteria in
      most of the ecosystems. Specially in oceans, viruses are thought to be the major
      planktonic predators shaping microorganism communities and controlling ocean
      biological capacity. Plankton lysis by viruses plays an important role in ocean
      nutrient and energy cycles. Viral metagenomics has emerged as a powerful tool to
      uncover viral diversity in aquatic ecosystems through the use of Next Generation
      Sequencing. However, many of the commonly used viral sample preparation steps
      have several important biases that must be considered to avoid a
      misinterpretation of the results. In addition to biases caused by the
      purification of virus particles, viral DNA/RNA amplification and the preparation
      of genomic libraries could also introduce biases, and a detailed knowledge about
      such protocols is required. In this review, the main steps in the viral
      metagenomic workflow are described paying special attention to the potential
      biases introduced by each one.

PMID- 27889618
TI  - Cell death mechanistic study of photodynamic therapy against breast cancer cells
      utilizing liposomal delivery of 5,10,15,20-tetrakis(benzo[b]thiophene) porphyrin.
AB  - 5,10,15,20-Tetrakis(benzo[b]thiophene) porphyrin (BTP) is a newly synthesized
      hydrophobic photosensitizer with fluorescence quantum yield in toluene:
      PhiF=0.062. Previously, its limitations in solubility had hindered scientific
      experimentation regarding its photodynamic effects on cancer cells. By utilizing
      various compositions of liposomes in order to alter the solubility of BTP, the
      photocytotoxicity, reactive oxygen species generation, and subcellular
      localization of the liposomal BTP were identified in this work. DNA fragmentation
      and high content screening assays were performed in order to shed light on the
      tumoricidal mechanism of the liposomal photosensitizer. The MTT assay results
      showed promising results in the irradiation specific PDT activity against MCF-7
      cells in all liposomal compositions. Production of ROS was confirmed in the
      liposomal BTP treated MCF-7 cells after irradiation in a concentration dependent
      manner. The subcellular localization assays revealed that the localization of BTP
      was dependent on both the photosensitizer's chemical properties and the
      properties of the delivery agent encapsulating aforesaid substance. Significant
      DNA fragmentation was observed in both nucleus localizing liposomal BTP, BTP
      encapsulated DOPC and DOPE (DOPC-BTP and DOPE-BTP), treated MCF-7 cells. All
      liposomal-BTPs were successful in inducing mitochondrial permeability transition,
      an increase in the permeability of the mitochondrial membrane, and activating
      caspase-3/7. ER localizing BTP were able to significantly increase the cytosolic
      calcium levels by photodynamic therapy, confirming the photodynamic ability of ER
      localized BTP to damage the ER membrane. The application of liposomes in
      delivering a novel hydrophobic photosensitizer, BTP, and photodynamic therapy
      treatment against MCF-7 cells were successful. It was confirmed that the MCF-7
      cell death pathway via photodynamic therapy was altered in a controlled manner by
      controlling the intracellular localization of the photosensitizer through lipid
      composition adjustment.

PMID- 27889619
TI  - Selective motor control correlates with gait abnormality in children with
      cerebral palsy.
AB  - Children with bilateral cerebral palsy (CP) commonly have limited selective motor
      control (SMC). This affects their ability to complete functional tasks. The
      impact of impaired SMC on walking has yet to be fully understood. Measures of SMC
      have been shown to correlate with specific characteristics of gait, however the
      impact of SMC on overall gait pattern has not been reported. This study explored
      SMC data collected as part of routine gait analysis in children with bilateral
      CP. As part of their clinical assessment, SMC was measured with the Selective
      Control Assessment of the Lower Extremities (SCALE) in 194 patients with
      bilateral cerebral palsy attending for clinical gait analysis at a single centre.
      Their summed SCALE score was compared with overall gait impairment, as measured
      by Gait Profile Score (GPS). Score on SCALE showed a significant negative
      correlation with GPS (rs=-0.603, p<0.001). Cerebral injuries in CP result in
      damage to the motor tracts responsible for SMC. Our results indicate that this
      damage is also associated with changes in the development of walking pattern in
      children with CP.

PMID- 27889616
TI  - Developments in L2-based human papillomavirus (HPV) vaccines.
AB  - Infections with sexually transmitted high-risk Human Papillomavirus (hrHPV), of
      which there are at least 15 genotypes, are responsible for a tremendous disease
      burden by causing cervical, and subsets of other ano-genital and oro-pharyngeal
      carcinomas, together representing 5% of all cancer cases worldwide. HPV subunit
      vaccines consisting of virus-like particles (VLP) self-assembled from major
      capsid protein L1 plus adjuvant have been licensed. Prophylactic vaccinations
      with the 2-valent (HPV16/18), 4-valent (HPV6/11/16/18), or 9-valent
      (HPV6/11/16/18/31/33/45/52/58) vaccine induce high-titer neutralizing antibodies
      restricted to the vaccine types that cause up to 90% of cervical carcinomas, a
      subset of other ano-genital and oro-pharyngeal cancers and 90% of benign ano
      genital warts (condylomata). The complexity of manufacturing multivalent L1-VLP
      vaccines limits the number of included VLP types and thus the vaccines' spectrum
      of protection, leaving a panel of oncogenic mucosal HPV unaddressed. In addition,
      current vaccines do not protect against cutaneous HPV types causing benign skin
      warts, or against beta-papillomavirus (betaPV) types implicated in the
      development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. In
      contrast with L1-VLP, the minor capsid protein L2 contains type-common epitopes
      that induce low-titer yet broadly cross-neutralizing antibodies to heterologous
      PV types and provide cross-protection in animal challenge models. Efforts to
      increase the low immunogenicity of L2 (poly)-peptides and thereby to develop
      broader-spectrum HPV vaccines are the focus of this review.

PMID- 27889620
TI  - The Fli-1 transcription factor is a critical regulator for controlling the
      expression of chemokine C-X-C motif ligand 2 (CXCL2).
AB  - Mammalian cells produce inflammatory cytokines and chemokines in response to
      innate immune signals and their expression is tightly regulated. Chemokine (C-X-C
      motif) ligand 2 (CXCL2), also known as macrophage inflammatory protein 2-alpha
      (MIP2-alpha), is an inflammatory chemokine belonging to the CXC chemokine family.
      CXCL2 is chemotactic for neutrophils and elevated expression of CXCL2 is
      associated with many inflammatory and autoimmune diseases. The Fli-1 gene belongs
      to the large Ets transcription factor family, whose members regulate a wide
      variety of cellular functions including the immune response. In this study, we
      demonstrate that endothelial cells transfected with Fli-1 specific siRNA produce
      significantly less CXCL2 compared to cells transfected with control siRNA after
      stimulation by the Toll-like receptor (TLR) 4 ligands, lipopolysaccharide (LPS)
      and tumor necrosis factor alpha (TNF-alpha). The production of CXCL2 in
      endothelial cells stimulated with LPS stimulation is dose-dependent. We found
      that Fli-1 binds to the CXCL2 promoter as established by Chromatin
      immunoprecipitation (ChIP) assay. Transient transfection assays show that Fli-1
      drives transcription from the CXCL2 promoter in a dose-dependent manner and Fli-1
      regulates the expression of CXCL2 largely by directly binding to the promoter.
      Targeted knockdown and transient transfection experiments suggest that both Fli-1
      and the p65 subunit of NF-kappaB affect the activation of CXCL2 in an additive
      manner. These results indicate that Fli-1 is a novel, critical transcription
      factor that regulates the expression of the inflammatory chemokine CXCL2.

PMID- 27889621
TI  - Identifying non-toxic doses of manganese for manganese-enhanced magnetic
      resonance imaging to map brain areas activated by operant behavior in trained
      rats.
AB  - Manganese-enhanced magnetic resonance imaging (MEMRI) offers unique advantages
      such as studying brain activation in freely moving rats, but its usefulness has
      not been previously evaluated during operant behavior training. Manganese in a
      form of MnCl2, at a dose of 20mg/kg, was intraperitoneally infused. The
      administration was repeated and separated by 24h to reach the dose of 40mg/kg or
      60mg/kg, respectively. Hepatotoxicity of the MnCl2 was evaluated by determining
      serum aspartate aminotransferase, alanine aminotransferase, total bilirubin,
      albumin and protein levels. Neurological examination was also carried out. The
      animals were tested in visual cue discriminated operant task. Imaging was
      performed using a 3T clinical MR scanner. T1 values were determined before and
      after MnCl2 administrations. Manganese-enhanced images of each animal were
      subtracted from their baseline images to calculate decrease in the T1 value
      (DeltaT1) voxel by voxel. The subtracted T1 maps of trained animals performing
      visual cue discriminated operant task, and those of naive rats were compared. The
      dose of 60mg/kg MnCl2 showed hepatotoxic effect, but even these animals did not
      exhibit neurological symptoms. The dose of 20 and 40mg/kg MnCl2 increased the
      number of omissions and did not affect the accuracy of performing the visual cue
      discriminated operant task. Using the accumulated dose of 40mg/kg, voxels with a
      significant enhanced DeltaT1 value were detected in the following brain areas of
      the visual cue discriminated operant behavior performed animals compared to those
      in the controls: the visual, somatosensory, motor and premotor cortices, the
      insula, cingulate, ectorhinal, entorhinal, perirhinal and piriform cortices,
      hippocampus, amygdala with amygdalohippocampal areas, dorsal striatum, nucleus
      accumbens core, substantia nigra, and retrorubral field. In conclusion, the MEMRI
      proved to be a reliable method to accomplish brain activity mapping in
      correlation with the operant behavior of freely moving rodents.

PMID- 27889622
TI  - Evaluating UV-C LED disinfection performance and investigating potential dual
      wavelength synergy.
AB  - A dual-wavelength UV-C LED unit, emitting at peaks of 260 nm, 280 nm, and the
      combination of 260|280 nm together was evaluated for its inactivation efficacy
      and energy efficiency at disinfecting Escherichia coli, MS2 coliphage, human
      adenovirus type 2 (HAdV2), and Bacillus pumilus spores, compared to conventional
      low-pressure and medium-pressure UV mercury vapor lamps. The dual-wavelength unit
      was also used to measure potential synergistic effects of multiple wavelengths on
      bacterial and viral inactivation and DNA and RNA damage. All five UV sources
      demonstrated similar inactivation of E. coli. For MS2, the 260 nm LED was most
      effective. For HAdV2 and B. pumilus, the MP UV lamp was most effective. When
      measuring electrical energy per order of reduction, the LP UV lamp was most
      efficient for inactivating E. coli and MS2; the LP UV and MP UV mercury lamps
      were equally efficient for HAdV2 and B. pumilus spores. Among the UV-C LEDs,
      there was no statistical difference in electrical efficiency for inactivating
      MS2, HAdV2, and B. pumilus spores. The 260 nm and 260|280 nm LEDs had a
      statistical energy advantage for E. coli inactivation. For UV-C LEDs to match the
      electrical efficiency per order of log reduction of conventional LP UV sources,
      they must reach efficiencies of 25-39% or be improved on by smart reactor design.
      No dual wavelength synergies were detected for bacterial and viral inactivation
      nor for DNA and RNA damage.

PMID- 27889623
TI  - Training needs of clinical nurses at an university hospital in Turkey.
AB  - The learning needs of clinical nurses should be determined and evaluated at
      regular intervals for evaluate the continuity and the efficiency of education.
      The descriptive study was conducted to determine the training needs of nurses
      working in an educational hospital between February 1st 2012 and May 1st 2012. It
      was determined that, among the training topics related to patient care, those
      demanded the most were cardio-pulmonary resuscitation, fluid-electrolyte balance,
      safe drug administration and wound Care. As for the topics related to management
      skills, the nurses stated that they needed training especially on stress and
      crisis management. The results of the present study suggest that in-service
      training is necessary in the clinical field and training programs, which should
      be aimed to ensure the participation of; nurses in in-service training sessions
      to the maximum extent possible, are needed.

PMID- 27889624
TI  - Stress and anxiety among nursing students: A review of intervention strategies in
      literature between 2009 and 2015.
AB  - Undergraduate nursing students experience significant stress and anxiety,
      inhibiting learning and increasing attrition. Twenty-six intervention studies
      were identified and evaluated, updating a previous systematic review which
      categorized interventions targeting: (1) stressors, (2) coping, or (3) appraisal.
      The majority of interventions in this review aimed to reduce numbers or intensity
      of stressors through curriculum development (12) or to improve students' coping
      skills (8). Two studies reported interventions using only cognitive reappraisal
      while three interventions combined reappraisal with other approaches. Strength of
      evidence was limited by choice of study design, sample size, and lack of
      methodological rigor. Some statistically significant support was found for
      interventions focused on reducing stressors through curriculum development or
      improving students' coping skills. No statistically significant studies using
      reappraisal, either alone or in combination with other approaches, were
      identified, although qualitative findings suggested the potential benefits of
      this approach do merit further study. Progress was noted since 2008 in the
      increased number of studies and greater use of validated outcome measures but the
      review concluded further methodologically sound, adequately powered studies,
      especially randomized controlled trials, are needed to determine which
      interventions are effective to address the issue of excessive stress and anxiety
      among undergraduate nursing students.

PMID- 27889625
TI  - Cortical interneuron specification: the juncture of genes, time and geometry.
AB  - A fundamental question in developmental neuroscience is how hundreds of diverse
      cell types are generated to form specialized brain regions. The ganglionic
      eminences (GEs) are embryonic brain structures located in the ventral
      telencephalon that produce many inhibitory GABA (gamma-Aminobutyric acid)-ergic
      cell types, including long-range projection neurons and local interneurons (INs),
      which disperse widely throughout the brain. While much has been discovered about
      the origin and wiring of these cells, a major question remains: how do neurons
      originating in the GEs become specified during development as one differentiated
      subtype versus another? This review will cover recent work that has advanced our
      knowledge of the mechanisms governing cortical interneuron subtype specification,
      particularly progenitors' spatial origin, birthdates, lineage, and mode of
      division.

PMID- 27889627
TI  - Subthalamic oscillations and phase amplitude coupling are greater in the more
      affected hemisphere in Parkinson's disease.
AB  - OBJECTIVE: Determine the incidence of resting state oscillations in alpha/beta,
      high frequency (HFO) bands, and their phase amplitude coupling (PAC) in a large
      cohort in Parkinson's disease (PD). METHODS: Intra-operative local field
      potentials (LFPs) from subthalamic nucleus (STN) were recorded from 100 PD
      subjects, data from 74 subjects were included in the analysis. RESULTS:
      Alpha/beta oscillations were evident in >99%, HFO in 87% and PAC in 98% of cases.
      Alpha/beta oscillations (P<0.01) and PAC were stronger in the more affected (MA)
      hemisphere (P=0.03). Alpha/beta oscillations were primarily found in 13-20Hz (low
      beta). Beta and HFO frequencies with the greatest coupling, were positively
      correlated (P=0.001). Tremor attenuated alpha (P=0.002) and beta band
      oscillations (P<0.001). CONCLUSIONS: STN alpha/beta band oscillations and PAC
      were evident in ?98% cases and were greater in MA hemisphere. Resting tremor
      attenuated underlying alpha/beta band oscillations. SIGNIFICANCE: Beta band LFP
      power may be used to drive adaptive deep brain stimulation (aDBS), augmented by a
      kinematic classifier in tremor dominant PD.

PMID- 27889626
TI  - Absence of kynurenine 3-monooxygenase reduces mortality of acute viral
      myocarditis in mice.
AB  - Infection of the encephalomyocarditis virus (EMCV) in mice is an established
      model for viral myocarditis. Previously, we have demonstrated that indoleamine
      2,3-dioxygenase (IDO), an L-tryptophan - kynurenine pathway (KP) enzyme, affects
      acute viral myocarditis. However, the roles of KP metabolites in EMCV infection
      remain unclear. Kynurenine 3-monooxygenase (KMO) is one of the key regulatory
      enzymes, which metabolizes kynurenine to 3-hydroxykynurenine in the KP.
      Therefore, we examined the role of KMO in acute viral infection by comparing
      between KMO-/- mice and KMO+/+ mice. KMO deficiency resulted in suppressed
      mortality after EMCV infection. The number of infiltrating cells and F4/80+ cells
      in KMO-/- mice was suppressed compared with those in KMO+/+ mice. KMO-/- mice
      showed significantly increased levels of serum KP metabolites, and induction of
      KMO expression upon EMCV infection was involved in its effect on mortality
      through EMCV suppression. Furthermore, KMO-/- mice showed significantly
      suppression of CCL2, CCL3 and CCL4 on day 2 and CXCL1 on day 4 after infection.
      These results suggest that increased KP metabolites reduced chemokine production,
      resulting in suppressed mortality upon KMO knockdown in EMCV infection. KP
      metabolites may thus provide an effective strategy for treating acute viral
      myocarditis.

PMID- 27889628
TI  - Effect of betel nut chewing on the otolithic reflex system.
AB  - OBJECTIVE: This study investigated the effect of betel nut chewing on the
      otolithic reflex system. METHODS: Seventeen healthy volunteers without any
      experience of chewing betel nut (fresh chewers) and 17 habitual chewers underwent
      vital sign measurements, ocular vestibular-evoked myogenic potential (oVEMP), and
      cervical VEMP (cVEMP) tests prior to the study. Each subject then chewed two
      pieces of betel nut for 2min (dosing). The same paradigm was repeated
      immediately, 10min, and 20min after chewing. On a different day, 10 fresh chewers
      masticated chewing gum as control. RESULTS: Fresh chewers exhibited significantly
      decreased response rates of oVEMP (53%) and cVEMP (71%) after dosing compared
      with those from the predosing period. These abnormal VEMPs returned to normal
      20min after dosing. In contrast, 100% response rates of oVEMP and cVEMP were
      observed before and after masticating chewing gum. In habitual chewers, the
      response rates of oVEMP and cVEMP were 32% and 29%, respectively, 20min after
      dosing. CONCLUSION: Chewing betel nuts induced a transient loss of the otolithic
      reflexes in fresh chewers but may cause permanent loss in habitual chewers.
      SIGNIFICANCE: Chewing betel nuts can cause a loss of otholitic reflex function.
      This creates a risk for disturbed balance and malfunction, for instance, during
      driving.

PMID- 27889629
TI  - Terminal functionalized thiourea-containing dipeptides as multidrug-resistance
      reversers that target 20S proteasome and cell proliferation.
AB  - A series of inhibitors of 20S proteasome based on terminal functionalized
      dipeptide derivatives containing the thiourea moiety were synthesized and
      evaluated for inhibition of 20S proteasome and the effects of multidrug
      resistance reversers. These compounds exhibited significant selectivity to the
      beta5-subunit of the human 20S proteasome with IC50 values at submicromolar
      concentrations. A docking study of the most active compound 6i revealed key
      interactions between 6i and the active site of the 20S proteasome in which the
      thiourea moiety and a nitro group were important for improving activity. In
      particular, compound 6i appeared to be the most potent compound against the NCI
      H460 cell line, and displayed similar efficiency in drug-sensitive versus drug
      resistant cancer cell lines, at least partly, by inhibition of the activity of
      20S proteasome and induce apoptosis. In addition, 6i-induced apoptosis was
      significantly facilitated in NCI-H460/DOX cells that had been pretreated with
      inhibitors of P-gp. Mechanistically, compound 6i might trigger apoptotic
      signalling pathway. Thus, we conclude that dipeptide derivatives containing the
      thiourea moiety may be the potential inhibitors of proteasome with the ability to
      reverse multidrug resistance.

PMID- 27889630
TI  - 1,2,3-Triazolyl ester of Ketorolac: A "Click Chemistry"-based highly potent PAK1
      blocking cancer-killer.
AB  - An old anti-inflammatory/analgesic drug called Toradol is a racemic form of
      Ketorolac (50% R-form and 50% S-form) that blocks the oncogenic RAC-PAK1-COX-2
      (cyclooxygenase-2) signaling, through the direct inhibition of RAC by the R-form
      and of COX-2 by the S-form, eventually down-regulating the production of
      prostaglandins. However, due to its COOH moiety which is clearly repulsive to
      negatively-charged phospholipid-based plasma membrane, its cell-permeability is
      rather poor (the IC50 against the growth of human cancer cells such as A549 is
      around 13 MUM). In an attempt to boost its anti-cancer activity, hopefully by
      increasing its cell-permeability through abolishing the negative charge, yet
      keeping its water-solubility, here we synthesized a 1,2,3-triazolyl ester of
      Toradol through "Click Chemistry". The resultant water-soluble "azo" derivative
      called "15K" was found to be over 500 times more potent than Toradol with the
      IC50 around 24 nM against the PAK1-dependent growth of A549 cancer cells,
      inactivating PAK1 in cell culture with the apparent IC50 around 65 nM, and
      inhibiting COX-2 in vitro with the IC50 around 6 nM. Furthermore, the Click
      Chemistry boosts the anti-cancer activity of Ketorolac by 5000 times against the
      PAK1-independent growth of B16F10 melanoma cells. Using a multi-drug-resistant
      (MDR) cancer cell line (EMT6), we found that the esterization of Ketorolac boosts
      its cell-permeability by at least 10 folds. Thus, the Click Chemistry
      dramatically boosts the anti-cancer activity of Ketorolac, at least in three
      ways: increasing its cell-permeability, the anti-PAK1 activity of R-form and anti
      COX-2 activity of S-form. The resultant "15K" is so far among the most potent
      PAK1-blockers, and therefore would be potentially useful for the therapy of many
      different PAK1-dependent diseases/disorders such as cancers.

PMID- 27889631
TI  - Design, synthesis and cytotoxicity studies of novel pyrazolo[1, 5-a]pyridine
      derivatives.
AB  - Copper-mediated synthesis of various pyrazolo[1, 5-a]pyridine-3-carboxylates has
      been described. The biological activities of these molecules have been evaluated
      against various human cancer cell lines A549 (Lung adenocarcinoma cell line), MCF
      7 (Breast carcinoma cell line), HCT-116 (Colon cancer cell line), and PC-3
      (Prostate cancer cell line) through SRB assay. Compound 247 led to accumulation
      MCF-7 cells in G1-phase and revealed its important role in mitotic cell cycle
      progression.

PMID- 27889632
TI  - Synthesis, biological evaluation and in silico molecular modeling of pyrrolyl
      benzohydrazide derivatives as enoyl ACP reductase inhibitors.
AB  - In efforts to develop lead anti-TB compounds, a novel series of 19 pyrrolyl
      benzohydrazides were synthesized and screened to target enoyl-ACP reductase
      enzyme, which is one of the important enzymes involved in type II fatty acid
      biosynthetic pathway of M. tuberculosis. Pharmacophores were constructed using
      GALAHAD to generate alignment of data sets and calculated by Pareto ranking. The
      pharmacophore features were then filtered by Surflex-dock study using enoyl ACP
      reductase from M. tuberculosis. Compounds 5b and 5d showed H-bonding interactions
      with Tyr158, Thr196 and co-factor NAD+ that fitted well within the binding pocket
      of InhA. All the synthesized compounds were screened for preliminary
      antibacterial activities against Gram-positive S. aureus and Gram-negative E.
      coli and M. tuberculosis H37Rv to evaluate their antitubercular activities. Some
      representative compounds were further tested for mammalian cell toxicity using
      human lung cancer cell-line (A549) that was found to be nontoxic. These compounds
      exhibited moderate inhibition activities against InhA.

PMID- 27889633
TI  - Effects of state contraceptive insurance mandates.
AB  - Using U.S. Natality data for 1996 through 2009 and an event analysis
      specification, we investigate the dynamics of the effects of state insurance
      contraceptive mandates on births and measures of parental investment: prenatal
      visits, non-marital childbearing, and risky behaviors during pregnancy. We
      analyze outcomes separately by age, race, and ethnicity. Among young Hispanic
      women, we find a 4% decline in the birth rate. There is evidence of a decrease in
      births to single mothers, consistent with increased wantedness. We also find
      evidence of selection into motherhood, which could explain the lack of a
      significant effect on birth outcomes.

PMID- 27889634
TI  - Obesity: A major problem for Spanish minors.

PMID- 27889635
TI  - Plasmodesmata enable multicellularity: new insights into their evolution,
      biogenesis, and functions in development and immunity.
AB  - Plant cells are connected by plasmodesmata (PD), cytosolic bridges that allow
      molecules to freely move across the cell wall. Recently resolved relationships
      among land plants and their algal relatives reveal that land plants evolved PD
      independently from algae. Proteomic and genetic screens illuminate new dimensions
      of the structural and regulatory pathways that control PD biogenesis. Biochemical
      studies demonstrate that immunological signals induce systemic defenses by moving
      from diseased cells through PD; subsequently, PD transport is restricted to
      quarantine diseased cells. Here, we review our expanding knowledge of the roles
      of PD in plant development, physiology, and immunity.

PMID- 27889636
TI  - Locating light and heavy atomic column positions with picometer precision using
      ISTEM.
AB  - Recently, imaging scanning transmission electron microscopy (ISTEM) has been
      proposed as a promising new technique combining the advantages of conventional
      TEM (CTEM) and STEM (Rosenauer et al., 2014 [1]). The ability to visualize light
      and heavy elements together makes it a particularly interesting new, spatially
      incoherent imaging mode. Here, we evaluate this technique in term of precision
      with which atomic column locations can be measured. By using statistical
      parameter estimation theory, we will show that these locations can be accurately
      measured with a precision in the picometer range. Furthermore, a quantitative
      comparison is made with HAADF STEM imaging to investigate the advantages of
      ISTEM.

PMID- 27889637
TI  - Cell membrane modulation as adjuvant in cancer therapy.
AB  - Cancer is a complex disease involving numerous biological processes, which can
      exist in parallel, can be complementary, or are engaged when needed and as such
      can replace each other. This redundancy in possibilities cancer cells have, are
      fundamental to failure of therapy. However, intrinsic features of tumor cells and
      tumors as a whole provide also opportunities for therapy. Here we discuss the
      unique and specific makeup and arrangement of cell membranes of tumor cells and
      how these may help treatment. Interestingly, knowledge on cell membranes and
      associated structures is present already for decades, while application of
      membrane modification and manipulation as part of cancer therapy is lagging.
      Recent developments of scientific tools concerning lipids and lipid metabolism,
      opened new and previously unknown aspects of tumor cells and indicate possible
      differences in lipid composition and membrane function of tumor cells compared to
      healthy cells. This field, coined Lipidomics, demonstrates the importance of
      lipid components in cell membrane in several illnesses. Important alterations in
      cancer, and specially in resistant cancer cells compared to normal cells, opened
      the door to new therapeutic strategies. Moreover, the ability to modulate
      membrane components and/or properties has become a reality. Here, developments in
      cancer-related Lipidomics and strategies to interfere specifically with cancer
      cell membranes and how these affect cancer treatment are discussed. We
      hypothesize that combination of lipid or membrane targeted strategies with
      available care to improve chemotherapy, radiotherapy and immunotherapy will bring
      the much needed change in treatment in the years to come.

PMID- 27889638
TI  - Identification of caleosin and oleosin in oil bodies of pine pollen.
AB  - Unique proteins including steroleosin, caleosin, oleosin-L, and oleosin-G have
      been identified in seed oil bodies of pine (Pinus massoniana). In this study,
      mature pollen grains with wing-like bladders were collected from pine (Pinus
      elliottii). Ultrastructural studies showed that oil bodies were present in pollen
      grains, but not the attached bladders, and the presence of oil bodies was further
      confirmed by fluorescent staining with BODIPY 493/503. Stable oil bodies were
      successfully purified from pine pollen grains, and analyzed to be mainly composed
      of triacylglycerols. Putative oleosin and caleosin in pine pollen oil bodies were
      detected by immunoassaying with antibodies against sesame seed caleosin and lily
      pollen oleosin. Complete cDNA fragments encoding these two pollen oil-body
      proteins were obtained by PCR cloning. Sequence alignment showed that pine pollen
      caleosin (27 kDa) was highly homologous to pine seed caleosin (28 kDa) except for
      the lack of an appendix of eight residues at the C-terminus in accord with the 1
      kDa difference in their molecular masses. Pine pollen oleosin (15 kDa) was highly
      homologous to pine seed oleosin-G (14 kDa) except for an insertion of eight
      residues at the N-terminus in accord with the 1 kDa difference in their molecular
      masses.

PMID- 27889639
TI  - Sulforaphane is a Nrf2-independent inhibitor of mitochondrial fission.
AB  - The KEAP1-Nrf2-ARE antioxidant system is a principal means by which cells respond
      to oxidative and xenobiotic stresses. Sulforaphane (SFN), an electrophilic
      isothiocyanate derived from cruciferous vegetables, activates the KEAP1-Nrf2-ARE
      pathway and has become a molecule-of-interest in the treatment of diseases in
      which chronic oxidative stress plays a major etiological role. We demonstrate
      here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1)
      cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and
      its cytoplasmic inhibitor KEAP1. Mitochondrial fusion has been reported to be
      cytoprotective by inhibiting pore formation in mitochondria during apoptosis, and
      consistent with this, we show Nrf2-independent, cytoprotection of SFN-treated
      cells exposed to the apoptosis-inducer, staurosporine. Mechanistically, SFN
      mitigates the recruitment and/or retention of the soluble fission factor Drp1 to
      mitochondria and to peroxisomes but does not affect overall Drp1 abundance. These
      data demonstrate that the beneficial properties of SFN extend beyond activation
      of the KEAP1-Nrf2-ARE system and warrant further interrogation given the current
      use of this agent in multiple clinical trials.

PMID- 27889640
TI  - Inhibition of autophagy with bafilomycin and chloroquine decreases mitochondrial
      quality and bioenergetic function in primary neurons.
AB  - Autophagy is an important cell recycling program responsible for the clearance of
      damaged or long-lived proteins and organelles. Pharmacological modulators of this
      pathway have been extensively utilized in a wide range of basic research and pre
      clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that
      inhibit autophagy by targeting the lysosomes but through distinct mechanisms.
      Since it is now clear that mitochondrial quality control, particularly in
      neurons, is dependent on autophagy, it is important to determine whether these
      compounds modify cellular bioenergetics. To address this, we cultured primary rat
      cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a
      targeted metabolomics approach to measure the effects of bafilomycin A1 and
      chloroquine on bioenergetics and metabolism. We found that both bafilomycin and
      chloroquine could significantly increase the autophagosome marker LC3-II and
      inhibit key parameters of mitochondrial function, and increase mtDNA damage.
      Furthermore, we observed significant alterations in TCA cycle intermediates,
      particularly those downstream of citrate synthase and those linked to
      glutaminolysis. Taken together, these data demonstrate a significant impact of
      bafilomycin and chloroquine on cellular bioenergetics and metabolism consistent
      with decreased mitochondrial quality associated with inhibition of autophagy.

PMID- 27889641
TI  - Increased mitochondrial superoxide in the brain, but not periphery, sensitizes
      mice to angiotensin II-mediated hypertension.
AB  - Angiotensin II (AngII) elicits the production of superoxide (O2*-) from
      mitochondria in numerous cell types within peripheral organs and in the brain
      suggesting a role for mitochondrial-produced O2*- in the pathogenesis of
      hypertension. However, it remains unclear if mitochondrial O2*- is causal in the
      development of AngII-induced hypertension, or if mitochondrial O2*- in the
      absence of elevated AngII is sufficient to increase blood pressure. Further, the
      tissue specific (i.e. central versus peripheral) redox regulation of AngII
      hypertension remains elusive. Herein, we hypothesized that increased
      mitochondrial O2*- in the absence of pro-hypertensive stimuli, such as AngII,
      elevates baseline systemic mean arterial pressure (MAP), and that AngII-mediated
      hypertension is exacerbated in animals with increased mitochondrial O2*- levels.
      To address this hypothesis, we generated novel inducible knock-down mouse models
      of manganese superoxide dismutase (MnSOD), the O2*- scavenging antioxidant enzyme
      specifically localized to mitochondria, targeted to either the brain subfornical
      organ (SFO) or peripheral tissues. Contrary to our hypothesis, knock-down of
      MnSOD either in the SFO or in peripheral tissues was not sufficient to alter
      baseline systemic MAP. Interestingly, when mice were challenged with chronic,
      peripheral infusion of AngII, only the MnSOD knock-down confined to the SFO, and
      not the periphery, demonstrated an increased sensitization and potentiated
      hypertension. In complementary experiments, over-expressing MnSOD in the SFO
      significantly decreased blood pressure in response to chronic AngII. Overall,
      these studies indicate that mitochondrial O2*- in the brain SFO works in concert
      with other AngII-dependent factors to drive an increase in MAP, as elevated
      mitochondrial O2*- alone, either in the SFO or peripheral tissues, failed to
      raise baseline blood pressure.

PMID- 27889643
TI  - Multimodality Imaging Identifies Distinct Metabolic Profiles In Vitro and In
      Vivo.
AB  - The study of alterations of tumor metabolism should allow the identification of
      new targets for innovative anticancer strategies. Metabolic alterations are
      generally established in vitro, and conclusions are often extrapolated to the in
      vivo situation without further tumor metabolic phenotyping. To highlight the key
      role of microenvironment on tumor metabolism, we studied the response of
      glycolytic and oxidative tumor models to metabolic modulations in vitro and in
      vivo. MDA-MB-231 and SiHa tumor models, characterized in vitro as glycolytic and
      oxidative, respectively, were studied. Theoretically, when passing from a hypoxic
      state to an oxygenated state, a Warburg phenotype should conserve a glycolytic
      metabolism, whereas an oxidative phenotype should switch from glycolytic to
      oxidative metabolism (Pasteur effect). This challenge was applied in vitro and in
      vivo to evaluate the impact of different oxic conditions on glucose metabolism.
      18F-fluorodeoxyglucose uptake, lactate production, tumor oxygenation, and
      metabolic fluxes were monitored in vivo using positron emission tomography,
      microdialysis, electron paramagnetic resonance imaging, and 13C-hyperpolarizated
      magnetic resonance spectroscopy, respectively. In vitro, MDA-MB-231 cells were
      glycolytic under both hypoxic and oxygenated conditions, whereas SiHa cells
      underwent a metabolic shift after reoxygenation. On the contrary, in vivo, the
      increase in tumor oxygenation (induced by carbogen challenge) led to a similar
      metabolic shift in glucose metabolism in both tumor models. The major discordance
      in metabolic patterns observed in vitro and in vivo highlights that any
      extrapolation of in vitro metabolic profiling to the in vivo situation should be
      taken cautiously and that metabolic phenotyping using molecular imaging is
      mandatory in vivo.

PMID- 27889644
TI  - Delineating the Role of betaIV-Tubulins in Pancreatic Cancer: betaIVb-Tubulin
      Inhibition Sensitizes Pancreatic Cancer Cells to Vinca Alkaloids.
AB  - Pancreatic cancer (PC) is a lethal disease which is characterized by
      chemoresistance. Components of the cell cytoskeleton are therapeutic targets in
      cancer. betaIV-tubulin is one such component that has two isotypes-betaIVa and
      betaIVb. betaIVa and betaIVb isotypes only differ in two amino acids at their C
      terminus. Studies have implicated betaIVa-tubulin or betaIVb-tubulin expression
      with chemoresistance in prostate, breast, ovarian and lung cancer. However, no
      studies have examined the role of betaIV-tubulin in PC or attempted to identify
      isotype specific roles in regulating cancer cell growth and chemosensitivity. We
      aimed to determine the role of betaIVa- or betaIVb-tubulin on PC growth and
      chemosensitivity. PC cells (MiaPaCa-2, HPAF-II, AsPC1) were treated with siRNA
      (control, betaIVa-tubulin or betaIVb-tubulin). The ability of PC cells to form
      colonies in the presence or absence of chemotherapy was measured by clonogenic
      assays. Inhibition of betaIVa-tubulin in PC cells had no effect chemosensitivity.
      In contrast, inhibition of betaIVb-tubulin in PC cells sensitized to vinca
      alkaloids (Vincristine, Vinorelbine and Vinblastine), which was accompanied by
      increased apoptosis and enhanced cell cycle arrest. We show for the first time
      that betaIVb-tubulin, but not betaIVa-tubulin, plays a role in regulating vinca
      alkaloid chemosensitivity in PC cells. The results from this study suggest
      betaIVb-tubulin may be a novel therapeutic target and predictor of vinca alkaloid
      sensitivity for PC and warrants further investigation.

PMID- 27889642
TI  - Redox control of senescence and age-related disease.
AB  - The signaling networks that drive the aging process, associated functional
      deterioration, and pathologies has captured the scientific community's attention
      for decades. While many theories exist to explain the aging process, the
      production of reactive oxygen species (ROS) provides a signaling link between
      engagement of cellular senescence and several age-associated pathologies.
      Cellular senescence has evolved to restrict tumor progression but the
      accompanying senescence-associated secretory phenotype (SASP) promotes pathogenic
      pathways. Here, we review known biological theories of aging and how ROS
      mechanistically control senescence and the aging process. We also describe the
      redox-regulated signaling networks controlling the SASP and its important role in
      driving age-related diseases. Finally, we discuss progress in designing
      therapeutic strategies that manipulate the cellular redox environment to restrict
      age-associated pathology.

PMID- 27889645
TI  - Suppression of Tumor Growth and Muscle Wasting in a Transgenic Mouse Model of
      Pancreatic Cancer by the Novel Histone Deacetylase Inhibitor AR-42.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of
      cancer death in the United States. This study was aimed at evaluating the
      efficacy of AR-42 (formerly OSU-HDAC42), a novel histone deacetylase (HDAC)
      inhibitor currently in clinical trials, in suppressing tumor growth and/or cancer
      induced muscle wasting in murine models of PDAC. EXPERIMENTAL DESIGN: The in
      vitro antiproliferative activity of AR-42 was evaluated in six human pancreatic
      cancer cell lines (AsPC-1, COLO-357, PANC-1, MiaPaCa-2, BxPC-3, SW1990). AsPC-1
      subcutaneous xenograft and transgenic KPfl/flC (LSL-KrasG12D;Trp53flox/flox;Pdx-1
      Cre) mouse models of pancreatic cancer were used to evaluate the in vivo efficacy
      of AR-42 in suppressing tumor growth and/or muscle wasting. RESULTS: Growth
      suppression in AR-42-treated cells was observed in all six human pancreatic
      cancer cell lines with dose-dependent modulation of proliferation and apoptotic
      markers, which was associated with the hallmark features of HDAC inhibition,
      including p21 upregulation and histone H3 hyperacetylation. Oral administration
      of AR-42 at 50 mg/kg every other day resulted in suppression of tumor burden in
      the AsPC-1 xenograft and KPfl/flC models by 78% and 55%, respectively, at the end
      of treatment. Tumor suppression was associated with HDAC inhibition, increased
      apoptosis, and inhibition of proliferation. Additionally, AR-42 as a single agent
      preserved muscle size and increased grip strength in KPfl/flC mice. Finally, the
      combination of AR-42 and gemcitabine in transgenic mice demonstrated a
      significant increase in survival than either agent alone. CONCLUSIONS: These
      results suggest that AR-42 represents a therapeutically promising strategy for
      the treatment of pancreatic cancer.

PMID- 27889648
TI  - PB2 substitutions V598T/I increase the virulence of H7N9 influenza A virus in
      mammals.
AB  - PB2 is one of the subunits of the influenza A virus (IAV) polymerase complex. By
      bioinformatics analysis we identified PB2 substitutions at positions 389 and 598
      among IAV isolates from humans, which might associate with viral pathogenicity.
      To evaluate the biological significance of these substitutions, PB2-K389R and 
      V598T/I mutant viruses of avian H7N9 IAVs were generated by reverse genetics.
      Compared to the wild type, the mutant viruses displayed an enhanced growth
      capacity in human and mammalian cells. Meanwhile, they presented increased
      transcription and replication by producing higher levels of viral mRNA, cRNA and
      vRNA. Minireplicon assays indicated that the polymerase activity was elevated by
      these substitutions. Notably, the PB2-V598T/I substitutions substantially
      increased virus replication and virulence in mice. Together, we demonstrated that
      the substitutions PB2-V598T/I contributed to higher IAV replication and virulence
      in mammals, which added to the knowledge of IAV virulence determinants and
      benefited the surveillance of IAVs.

PMID- 27889646
TI  - Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody
      Drug Conjugate, Potentiates the Activity of Standard of Care Therapeutics in
      Ovarian Cancer Models.
AB  - Elevated folate receptor alpha (FRalpha) expression is characteristic of
      epithelial ovarian cancer (EOC), thus establishing this receptor as a candidate
      target for the development of novel therapeutics to treat this disease.
      Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate (ADC) that
      targets FRalpha for tumor-directed delivery of the maytansinoid DM4, a potent
      agent that induces mitotic arrest by suppressing microtubule dynamics. Here,
      combinations of IMGN853 with approved therapeutics were evaluated in preclinical
      models of EOC. Combinations of IMGN853 with carboplatin or doxorubicin resulted
      in synergistic antiproliferative effects in the IGROV-1 ovarian cancer cell line
      in vitro. IMGN853 potentiated the cytotoxic activity of carboplatin via growth
      arrest and augmented DNA damage; cell cycle perturbations were also observed in
      cells treated with the IMGN853/doxorubicin combination. These benefits translated
      into improved antitumor activity in patient-derived xenograft models in vivo in
      both the platinum-sensitive (IMGN853/carboplatin) and platinum-resistant
      (IMGN853/pegylated liposomal doxorubicin) settings. IMGN853 co-treatment also
      improved the in vivo efficacy of bevacizumab in platinum-resistant EOC models,
      with combination regimens causing significant regressions and complete responses
      in the majority of tumor-bearing mice. Histological analysis of OV-90 ovarian
      xenograft tumors revealed that concurrent administration of IMGN853 and
      bevacizumab caused rapid disruption of tumor microvasculature and extensive
      necrosis, underscoring the superior bioactivity profile of the combination
      regimen. Overall, these demonstrations of combinatorial benefit conferred by the
      addition of the first FRalpha-targeting ADC to established therapies provide a
      compelling framework for the potential application of IMGN853 in the treatment of
      patients with advanced ovarian cancer.

PMID- 27889647
TI  - Activation of WNT/beta-Catenin Signaling Enhances Pancreatic Cancer Development
      and the Malignant Potential Via Up-regulation of Cyr61.
AB  - Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, commonly
      develops following activating mutations in the KRAS oncogene. Activation of WNT
      signaling is also commonly observed in PDAC. To ascertain the impact of postnatal
      activation of WNT-stimulated signaling pathways in PDAC development, we combined
      the Elastase-tva-based RCAS-TVA pancreatic cancer model with the established LSL
      KrasG12D, Ptf1a-cre model. Delivery of RCAS viruses encoding beta-cateninS37A and
      WNT1 stimulated the progression of premalignant pancreatic intraepithelial
      neoplasias (PanIN) and PDAC development. Moreover, mice injected with RCAS-beta
      cateninS37A or RCAS-Wnt1 had reduced survival relative to RCAS-GFP-injected
      controls (P<.05). Ectopic expression of active beta-catenin, or its DNA-binding
      partner TCF4, enhanced transformation associated phenotypes in PDAC cells. In
      contrast, these phenotypes were significantly impaired by the introduction of
      ICAT, an inhibitor of the beta-catenin/TCF4 interaction. By gene expression
      profiling, we identified Cyr61 as a target molecule of the WNT/beta-catenin
      signaling pathway in pancreatic cancer cells. Nuclear beta-catenin and CYR61
      expression were predominantly detected in moderately to poorly differentiated
      murine and human PDAC. Indeed, nuclear beta-catenin- and CYR61-positive PDAC
      patients demonstrated poor prognosis (P<.01). Knockdown of CYR61 in a beta
      catenin-activated pancreatic cancer cell line reduced soft agar, migration and
      invasion activity. Together, these data suggest that the WNT/beta-catenin
      signaling pathway enhances pancreatic cancer development and malignancy in part
      via up-regulation of CYR61.

PMID- 27889649
TI  - Heavy metal burdens of public primary school children related to playground soils
      and classroom dusts in Ibadan North-West local government area, Nigeria.
AB  - Information about heavy metal burden of children in Nigeria related to playground
      soils and classroom dusts is lacking. Playground soil, classroom dust, blood and
      spot urine samples (n=253) were collected from 6 urban and 2 semi-rural public
      schools in Ibadan North-West, Nigeria. Samples were analysed for Pb, Cu, Zn, Fe
      and Mn. Mean blood Pb levels in urban area (male, 41.66+/-8.78MUg/dl vs. female,
      40.64+/-5.46MUg/dl) were twice as high as those in semi-rural area (male, 19.71+/
      3.73MUg/dl vs. female, 20.65+/-2.26MUg/dl). Concentrations of Pb, Cu, Zn, and Fe
      in soil and dust samples in the urban schools were between 2- to 4-fold greater
      than that of semi-rural schools. No correlation was observed between blood and
      dust metals. A positive correlation (r=0.168, p=0.008) was observed between blood
      Pb and playground soil Pb. Pb burden in the children might be from their schools'
      playgrounds and other yet unidentified sources.

PMID- 27889650
TI  - Large dose hyperpolarized water with dissolution-DNP at high magnetic field.
AB  - We demonstrate a method for the preparation of hyperpolarized water by
      dissolution Dynamic Nuclear Polarization at high magnetic field. Protons were
      polarized at 6.7T and 1.1K to >70% with frequency modulated microwave irradiation
      at 188GHz. 97.2+/-0.7% of the radical was extracted from the sample in the
      dissolution in a two-phase system. 16+/-1mL of 5.0M 1H in D2O with a polarization
      of 13.0+/-0.9% in the liquid state was obtained, corresponding to an enhancement
      factor of 4000+/-300 compared to the thermal equilibrium at 9.4T and 293K. A
      longitudinal relaxation time constant of 16+/-1s was measured. The sample was
      polarized and dissolved in a fluid path compatible with clinical polarizers. The
      volume of hyperpolarized water produced by this method enables angiography and
      perfusion measurements in large animals, as well as NMR experiments for studies
      of e.g. proton exchange and polarization transfer to other nuclei.

PMID- 27889651
TI  - Effect of Rabi splitting on the low-temperature electron paramagnetic resonance
      signal of anthracite.
AB  - Specific distortions of the EPR signal of bulk anthracite are observed at low
      temperatures. They are accompanied by variations in the microwave oscillator
      frequency and are explained by the manifestation of the Rabi splitting due to the
      strong coupling between electron spins and the cavity, combined with the use of
      an automatic frequency-control (AFC) system. EPR signals are recorded at
      negligible saturation in the temperature range of 4-300K with use of the AFC
      system to keep the oscillator frequency locked to the resonant frequency of the
      TM110 cylinder cavity loaded with the sample. For the sample with a mass of 3.6mg
      the line distortions are observed below 50K and increase with temperature
      lowering. The oscillator frequency variations are used to estimate the coupling
      strength as well as the number of spins in the sample. It is shown that the spin
      cavity coupling strength is inversely proportional to temperature and can be used
      for the absolute determination of the number of spins in a sample. Our results
      indicate that at low temperatures even 1016 spins of the anthracite sample, with
      a mass of about 0.5mg, can distort the EPR line.

PMID- 27889652
TI  - Cloud GPU-based simulations for SQUAREMR.
AB  - Quantitative Magnetic Resonance Imaging (MRI) is a research tool, used more and
      more in clinical practice, as it provides objective information with respect to
      the tissues being imaged. Pixel-wise T1 quantification (T1 mapping) of the
      myocardium is one such application with diagnostic significance. A number of
      mapping sequences have been developed for myocardial T1 mapping with a wide range
      in terms of measurement accuracy and precision. Furthermore, measurement results
      obtained with these pulse sequences are affected by errors introduced by the
      particular acquisition parameters used. SQUAREMR is a new method which has the
      potential of improving the accuracy of these mapping sequences through the use of
      massively parallel simulations on Graphical Processing Units (GPUs) by taking
      into account different acquisition parameter sets. This method has been shown to
      be effective in myocardial T1 mapping; however, execution times may exceed 30min
      which is prohibitively long for clinical applications. The purpose of this study
      was to accelerate the construction of SQUAREMR's multi-parametric database to
      more clinically acceptable levels. The aim of this study was to develop a cloud
      based cluster in order to distribute the computational load to several GPU
      enabled nodes and accelerate SQUAREMR. This would accommodate high demands for
      computational resources without the need for major upfront equipment investment.
      Moreover, the parameter space explored by the simulations was optimized in order
      to reduce the computational load without compromising the T1 estimates compared
      to a non-optimized parameter space approach. A cloud-based cluster with 16 nodes
      resulted in a speedup of up to 13.5 times compared to a single-node execution.
      Finally, the optimized parameter set approach allowed for an execution time of
      28s using the 16-node cluster, without compromising the T1 estimates by more than
      10ms. The developed cloud-based cluster and optimization of the parameter set
      reduced the execution time of the simulations involved in constructing the
      SQUAREMR multi-parametric database thus bringing SQUAREMR's applicability within
      time frames that would be likely acceptable in the clinic.

PMID- 27889653
TI  - Remote detected Low-Field MRI using an optically pumped atomic magnetometer
      combined with a liquid cooled pre-polarization coil.
AB  - Superconducting quantum interference devices are widely used in basic and
      clinical biomagnetic measurements such as low-field magnetic resonance imaging
      and magnetoencephalography primarily because they exhibit high sensitivity at low
      frequencies and have a wide bandwidth. The main disadvantage of these devices is
      that they require cryogenic coolants, which are rather expensive and not easily
      available. Meanwhile, with the advances in laser technology in the past few
      years, optically pumped atomic magnetometers (OPAMs) have been shown to be a good
      alternative as they can have adequate noise levels and are several millimeters in
      size, which makes them significantly easier to use. In this study, we used an
      OPAM module operating at a Larmor frequency of 5kHz to acquire NMR and MRI
      signals. This study presents these initial results as well as our initial
      attempts at imaging using this OPAM module. In addition, we have designed a
      liquid-cooled pre-polarizing coil that reduces the measurement time
      significantly.

PMID- 27889654
TI  - Development of a sugar-binding residue prediction system from protein sequences
      using support vector machine.
AB  - Several methods have been proposed for protein-sugar binding site prediction
      using machine learning algorithms. However, they are not effective to learn
      various properties of binding site residues caused by various interactions
      between proteins and sugars. In this study, we classified sugars into acidic and
      nonacidic sugars and showed that their binding sites have different amino acid
      occurrence frequencies. By using this result, we developed sugar-binding residue
      predictors dedicated to the two classes of sugars: an acid sugar binding
      predictor and a nonacidic sugar binding predictor. We also developed a
      combination predictor which combines the results of the two predictors. We showed
      that when a sugar is known to be an acidic sugar, the acidic sugar binding
      predictor achieves the best performance, and showed that when a sugar is known to
      be a nonacidic sugar or is not known to be either of the two classes, the
      combination predictor achieves the best performance. Our method uses only amino
      acid sequences for prediction. Support vector machine was used as a machine
      learning algorithm and the position-specific scoring matrix created by the
      position-specific iterative basic local alignment search tool was used as the
      feature vector. We evaluated the performance of the predictors using five-fold
      cross-validation. We have launched our system, as an open source freeware tool on
      the GitHub repository (https://doi.org/10.5281/zenodo.61513).

PMID- 27889655
TI  - A Prediction Model Based on Biomarkers and Clinical Characteristics for Detection
      of Lung Cancer in Pulmonary Nodules.
AB  - Lung cancer early detection by low-dose computed tomography (LDCT) can reduce the
      mortality. However, LDCT increases the number of indeterminate pulmonary nodules
      (PNs), whereas 95% of the PNs are ultimately false positives. Modalities for
      specifically distinguishing between malignant and benign PNs are urgently needed.
      We previously identified a panel of peripheral blood mononucleated cell (PBMC)
      miRNA (miRs-19b-3p and -29b-3p) biomarkers for lung cancer. This study aimed to
      evaluate efficacy of integrating biomarkers and clinical and radiological
      characteristics of smokers for differentiating malignant from benign PNs. We
      analyzed expression of 2 miRNAs (miRs-19b-3p and -29b-3p) in PBMCs of a training
      set of 137 individuals with PNs. We used multivariate logistic regression
      analysis to develop a prediction model based on the biomarkers, radiographic
      features of PNs, and clinical characteristics of smokers for identifying
      malignant PNs. The performance of the prediction model was validated in a testing
      set of 111 subjects with PNs. A prediction model comprising the two biomarkers,
      spiculation of PNs and smoking pack-year, was developed that had 0.91 area under
      the curve of the receiver operating characteristic for distinguishing malignant
      from benign PNs. The prediction model yielded higher sensitivity (80.3% vs 72.6%)
      and specificity (89.4% vs 81.9%) compared with the biomarkers used alone (all
      P<.05). The performance of the prediction model for malignant PNs was confirmed
      in the validation set. We have for the first time demonstrated that the
      integration of biomarkers and clinical and radiological characteristics could
      efficiently identify lung cancer among indeterminate PNs.

PMID- 27889656
TI  - Safety effects of the London cycle superhighways on cycle collisions.
AB  - This paper evaluates the effects of the London Cycle Superhighways (CS) on cycle
      collisions. A total of 45 CS segments and 375 control segments are observed for a
      period of 8 years in London. Variables such as road characteristics, crash
      history and socio-economic information are included in the data set. Traffic
      characteristics including traffic volume, cycle volume and traffic speed are
      obtained from Department for Transport. We first estimate the safety effects on
      the CS routes using Empirical Bayes methods. Then propensity score matching
      methods are also applied for comparison. The introduction of cycle superhighways
      caused cycling traffic volumes to increase dramatically along CS routes with no
      significant impacts on collision rates. Our models find that the increase in
      traffic was associated with a rise in annual total cycle collisions of around 2.6
      per km (38% in percentage). However, when we re-estimate the effects based on
      cycle collision rates rather than levels, our results also show that the CS
      routes are not more dangerous or safer than the control roads. Among the four CS
      routes, CS3 performs the best in protecting cyclists with a large proportion of
      segregated lanes whilst the cyclists have to share the lanes with motorists on
      other routes. It is recommended that consistent safety designs should be applied
      on all CS routes for a safer cycling environment.

PMID- 27889657
TI  - Evaluation of fertilizer-drawn forward osmosis for sustainable agriculture and
      water reuse in arid regions.
AB  - The present study focused on the performance of the FDFO process to achieve
      simultaneous water reuse from wastewater and production of nutrient solution for
      hydroponic application. Bio-methane potential (BMP) measurements were firstly
      carried out to determine the effect of osmotic concentration of wastewater
      achieved in the FDFO process on the anaerobic activity. Results showed that 95%
      water recovery from the FDFO process is the optimum value for further AnMBR
      treatment. Nine different fertilizers were then tested based on their FO
      performance (i.e. water flux, water recovery and reverse salt flux) and final
      nutrient concentration. From this initial screening, ammonium phosphate monobasic
      (MAP), ammonium sulfate (SOA) and mono-potassium phosphate were selected for long
      term experiments to investigate the maximum water recovery achievable. After the
      experiments, hydraulic membrane cleaning was performed to assess the water flux
      recovery. SOA showed the highest water recovery rate, up to 76% while KH2PO4
      showed the highest water flux recovery, up to 75% and finally MAP showed the
      lowest final nutrient concentration. However, substantial dilution was still
      necessary to comply with the standards for fertigation even if the recovery rate
      was increased.

PMID- 27889658
TI  - Chlorella vulgaris cultivation in sludge extracts from 2,4,6-TCP wastewater
      treatment for toxicity removal and utilization.
AB  - Chlorella vulgaris was cultivated in different proportions of activated sludge
      extracts, which was from the treatment of the synthetic wastewater containing
      2,4,6-trichlorophenol (2,4,6-TCP). The nutrients, total nitrogen (TN) and total
      phosphorus (TP), were removed over 45% and 90%, respectively. The maximum
      reduction amount of ecotoxicity and total organic carbon (TOC) occurred in the
      100% sludge group on the 8th day (68%; 86.2 mg L-1). The variations of Excitation
      emission matrix spectra (EEMs) and TOC indicated that extracellular organic
      matters (EOM) produced by algae led to TOC increase in the medium. The cell
      density was close to each other for groups with sludge extract proportion below
      50%; sludge extracts (below 75% addition) had a stimulating effect on the
      accumulation of chlorophyll-a in per unit algal cell. Superoxide dismutase (SOD)
      variation demonstrated that C. vulgaris response positively to sludge extracts
      addition. Lipid content in C. vulgaris was up to its maximum value on the 8th
      day. Considering the performance on nutrients removal, toxicity reduction and
      algal growth, the optimal cultivation period for C. vulgaris before harvesting
      was around 8 days with sludge extracts proportion below 50%.

PMID- 27889659
TI  - A national riparian restoration programme in New Zealand: Is it value for money?
AB  - National scale initiatives are being attempted in New Zealand (NZ) to meet
      important environmental goals following land-use intensification over recent
      decades. Riparian restoration to filter agricultural spillover effects is
      currently the most widely practised mitigation measure but few studies have
      investigated the cumulative value of these practices at a national level. We use
      an applied economic land use model the benefits (GHG emissions, N leaching, P
      loss, sedimentation and biodiversity gain) and relevant costs (fencing,
      alternative stock water supplies, restoration planting and opportunity costs) of
      restoring riparian margins (5-50 m) on all streams in NZ flowing through current
      primary sector land. Extensive sensitivity analysis reveals that depending on
      margin width and cost assumptions, riparian margin restoration generates net
      benefits of between NZ$1.7 billion - $5.2 billion/yr and benefit-cost ratios
      ranging between 1.4 and 22.4. This suggests that even when not monetising the
      increase in biodiversity or components of stream ecosystem health and other
      benefits from planting riparian strips, the benefits to climate and freshwater
      are significantly greater than the implementation costs of riparian restoration.

PMID- 27889660
TI  - The pH-dependent leaching behavior of slags from various stages of a copper
      smelting process: Environmental implications.
AB  - The leaching behaviors of primary copper (Cu) slags originating from Ausmelt,
      reverbatory, and converter furnaces operating under a single technological
      process were compared to a residual slag tailing obtained by slag re-processing
      via flotation and metal recovery. The EN 12457-2 leaching test, used for
      assessment of the hazardous properties, was followed by the CEN/TS 14997 pH
      static leaching test (pH range 3-12). Both leaching experiments were coupled with
      a mineralogical investigation of the primary and secondary phases as well as
      geochemical modeling. Metals (Cd, Cu, Pb, Zn) exhibit the highest leaching at low
      pH. Under acidic conditions (pH 3-6), Ausmelt slag and slag tailing exhibited
      higher metal leaching compared to other slag types. Very low leaching of metals
      (far below EU limits for non-hazardous waste) was observed at natural pH (7.9
      9.0) for all the studied slag samples. In contrast, relatively high leaching of
      As was observed over the entire pH range, especially for Ausmelt slag (exceeding
      the EU limit for hazardous waste by 1.7*). However, geochemical modeling and
      scanning electron microscopy indicated that formation of stable Ca-Cu-Pb
      arsenates and the binding of As to newly formed Fe (oxyhydr)oxides play an
      important role in efficient As immobilization at the slag-water interface. In
      contrast, no controls were predicted for Sb, whose leaching was almost pH
      independent. Nevertheless Sb leached concentrations at natural pH were below EU
      limit for hazardous waste. Re-processing of primary Cu slags for metal recovery,
      and subsequent co-disposal of the resulting slag tailing with dolomite-rich mine
      tailing and local laterite is suitable for stabilizing the remaining contaminants
      (except Sb) and limiting their leaching into the environment.

PMID- 27889661
TI  - What explains the differences between centres in the European screening trial? A
      simulation study.
AB  - BACKGROUND: The European Randomised study of Screening for Prostate Cancer
      (ERSPC) is a multicentre, randomised screening trial on men aged 55-69 years at
      baseline without known prostate cancer (PrCa) at randomisation to an intervention
      arm invited to screening or to a control arm. The ERSPC has shown a significant
      21% reduction in PrCa mortality at 13 years of follow-up. The effect of screening
      appears to vary across centres, for which several explanations are possible. We
      set to assess if the apparent differences in PrCa mortality reduction between the
      centres can be explained by differences in screening protocols. METHODS: We
      examined the centre differences by developing a simulation model and estimated
      how alternative screening protocols would have affected PrCa mortality. RESULTS:
      Our results showed outcomes similar to those observed, when the results by
      centres were reproduced by simulating the screening regimens with PSA threshold
      of 3 versus 4ng/ml, or screening interval of two versus four years. The findings
      suggest that the differences are only marginally attributable to the different
      screening protocols. CONCLUSION: The small screening impact in Finland was not
      explained by the differences in the screening protocols. A possible reason for it
      was the contamination of and the unexpectedly low PrCa mortality in the Finnish
      control arm.

PMID- 27889662
TI  - Pediatric pineal germinomas: Epigenetic and genomic approach.
AB  - OBJECTIVE: We identify and correlate chromosomal alterations, methylation
      patterns and gene expression in pediatric pineal germinomas. METHODS: CGH
      microarray, methylation and gene expression were performed through the Agilent
      platform. The results were analyzed with MatLab software, MapViewer, DAVID,
      GeneCards and Hippie. RESULTS: Amplifications were found in 1q24.2, 1q31.3,
      2p11.2, 3p22.2, 7p13, 7p15.2, 8p22, 12p13.2, 14q24.3 y 22q12; and deletions were
      found in 1q21.2, 9p24.1, 10q11.22, 11q11, 15q11.2 and 17q21.31. In the
      methylation analysis, we observed 10,428 CpG Islands with a modified methylation
      status that may affect 11,726 genes. We identified 1260 overexpressed genes and
      470 underexpressed genes. The genes RUNDC3A, CDC247, CDCA7L, ASAH1, TRA2A, LPL
      and NPC2 were altered among the three levels. CONCLUSIONS: We identified the
      1q24.2 and 1q31.3 amplified regions and the 1q21.3 and 11q11 deleted regions as
      the most important aims. The genes NPC2 and ASAH1 may play an important role in
      the development, progression and tumor maintenance. The ASAH1 gene is an ideal
      candidate to identify drug responses. These genomic and epigenetic studies may
      help to characterize the formation of pineal germ cell tumors to determine
      prognostic markers and also to identify shared characteristics in gonadal and
      extragonadal tumors.

PMID- 27889663
TI  - Higher classification and phylogeny of Euglenozoa.
AB  - Discoveries of numerous new taxa and advances in ultrastructure and sequence
      phylogeny (including here the first site-heterogeneous 18S rDNA trees) require
      major improvements to euglenozoan higher-level taxonomy. I therefore divide
      Euglenozoa into three subphyla of substantially different body plans: Euglenoida
      with pellicular strips; anaerobic Postgaardia (class Postgaardea) dependent on
      surface bacteria and with uniquely modified feeding apparatuses; and new
      subphylum Glycomonada characterised by glycosomes (Kinetoplastea, Diplonemea).
      Euglenoida comprise two new infraphyla: Entosiphona with three feeding rods and
      Dipilida ancestrally with two. Dipilida comprise basal superclass Rigimonada with
      longitudinal rigid strips [i.e. new classes Stavomonadea (Petalomonadida,
      Decastavida and new order Heterostavida) and Ploeotarea (Ploeotiida) with
      contrasting oral cytoskeletons] and derived superclass Spirocuta with more
      numerous spirally arranged, often slideable, strips (clade
      Peranemea/Euglenophyceae) and a different, highly conserved microtubule pattern
      at strip joints. Peranemea comprise four orders: Peranemida (anterior gliding,
      protrusible rods), and three new, Anisonemida (posterior gliders), Natomonadida
      (swimmers including phagotrophic new suborder Metanemina and osmotrophic suborder
      Rhabdomonadina), and Acroglissida (anterior gliders with cytoproct). I establish
      orders Entosiphonida, Rapazida, Bihospitida; and seven new euglenoid families
      (Entosiphonidae, peranemean Neometanemidae, Rapazidae, two stavomonad, two
      ploeotiid) and three new postgaardian, and three kinetoplastid families
      (Neobodonidae, Rhynchomonadidae, Parabodonidae), plus new diplonemid family
      Hemistasiidae for Hemistasia.

PMID- 27889665
TI  - A three-dimensional spheroidal cancer model based on PEG-fibrinogen hydrogel
      microspheres.
AB  - Three-dimensional (3D) in vitro cancer models offer an attractive approach
      towards the investigation of tumorigenic phenomena and other cancer studies by
      providing dimensional context and higher degree of physiological relevance than
      that offered by conventional two-dimensional (2D) models. The multicellular tumor
      spheroid model, formed by cell aggregation, is considered to be the "gold
      standard" for 3D cancer models, due to its ease and simplicity of use. Although
      better than 2D models, tumor spheroids are unable to replicate key features of
      the native tumor microenvironment, particularly due to a lack of surrounding
      extracellular matrix components and heterogeneity in shape, size and aggregate
      forming tendencies. In order to address this issue, we have developed a 3D "tumor
      microsphere" model, formed by a dual-photoinitiator, aqueous-oil emulsion
      technique, for the encapsulation of cancer cells within PEG-fibrinogen hydrogel
      microspheres and for subsequent long-term 3D culture. In comparison to self
      aggregated tumor spheroids, the tumor microspheres displayed a higher degree of
      size and shape homogeneity throughout long-term culture. In sharp contrast to
      cells in tumor spheroids, cells within tumor microspheres demonstrated
      significant loss in apico-basal polarity and cellular architecture, cellular and
      nuclear atypia, increased disorganization, elevated nuclear cytoplasmic ratio and
      nuclear volume density and reduction in cell-cell junction length, all of which
      are hallmarks of malignant transformation and tumorigenic progression.
      Additionally, the tumor microsphere model was extended for the 3D encapsulation
      and maintenance of a wide range of other cancer cell (metastatic and non
      metastatic) types. Taken together, our results reinforce the importance of
      incorporating a biomimetic matrix in the cellular microenvironment of 3D tumor
      models and the influential effects of the matrix on the tumorigenic morphology of
      3D cultured cells. The tumor microsphere system established in this study has the
      potential to be used in future investigations of 3D cancer cell-cell and cell-ECM
      interactions and in drug-testing applications.

PMID- 27889664
TI  - Macrophage integrins modulate response to ultra-high molecular weight
      polyethylene particles and direct particle-induced osteolysis.
AB  - Aseptic loosening due to peri-prosthetic osteolysis is one of the primary causes
      for failure of artificial joint replacements. Implant-derived wear particles,
      often ultra-high molecular weight polyethylene (UHMWPE) microparticles, initiate
      an inflammatory cascade upon phagocytosis by macrophages, which leads to
      osteoclast recruitment and activation, ultimately resulting in osteolysis.
      Investigation into integrin receptors, involved in cellular interactions with
      biomaterial-adsorbed adhesive proteins, is of interest to understand and modulate
      inflammatory processes. In this work, we investigate the role of macrophage
      integrins Mac-1 and RGD-binding integrins in response to UHMWPE wear particles.
      Using integrin knockout mice as well as integrin blocking techniques, reduction
      in macrophage phagocytosis and inflammatory cytokine secretion is demonstrated
      when these receptors are either absent or blocked. Along this line, various
      opsonizing proteins are shown to differentially modulate microparticle uptake and
      macrophage secretion of inflammatory cytokines. Furthermore, using a calvarial
      osteolysis model it is demonstrated that both Mac-1 integrin and RGD-binding
      integrins modulate the particle induced osteolysis response to UHMWPE
      microparticles, with a 40% decrease in the area of osteolysis by the absence or
      blocking of these integrins, in vivo. Altogether, these findings indicate Mac-1
      and RGD-binding integrins are involved in macrophage-directed inflammatory
      responses to UHMWPE and may serve as therapeutic targets to mitigate wear
      particle induced peri-prosthetic osteolysis for improved performance of implanted
      joints.

PMID- 27889668
TI  - Drug-protein binding of Danhong injection and the potential influence of drug
      combination with aspirin: Insight by ultrafiltration LC-MS and molecular
      modeling.
AB  - Danhong injection (DHI) is a widely used Chinese medicine injection (CMI) for the
      clinical treatment of cardiovascular and cerebrovascular diseases. In this study,
      a simple and efficient in vitro method based on ultrafiltration LC-MS and
      molecular modeling has been developed to study the human serum albumin (HSA)
      binding of the compounds in DHI. Seven major components including protocatechuic
      aldehyde, p-coumaric acid, salvianolic acid D, rosmarinic acid, salvianolic acid
      E, lithospermic acid and salvianolic acid B were identified as HSA ligands and
      their binding degrees in the proposed non-saturated model were 26.17, 37.69,
      99.77, 91.78, 96.91, 99.42 and 98.10%, respectively. Considering the drug-HSA
      binding property of the compounds in DHI may change during drug combination
      therapy, competitive binding assay was carried out to evaluate the influence of
      aspirin on the DHI-HSA binding. Experimental results revealed that the
      salvianolic acids in DHI had stronger binding ability to HSA than sodium
      salicylate. To further verify the results above, molecular modeling and probe
      displacement assay were conducted to investigate the optimum binding site and
      binding affinity of the ligands on HSA. Our findings suggested that the
      established method could be a powerful tool to study the drug-HSA binding
      property of CMIs.

PMID- 27889667
TI  - The impact of a pulmonary recruitment maneuver to reduce post-laparoscopic
      shoulder pain: A randomized controlled trial.
AB  - OBJECTIVE: A pulmonary recruitment maneuver (PRM) can effectively reduce post
      laparoscopic shoulder pain (PLSP). However, a high-pressure PRM may cause
      pulmonary barotrauma. This study aimed to evaluate the efficacy and safety of a
      PRM using two different maximum inspiratory pressures (40 and 60cmH2O) for
      reducing PLSP. STUDY DESIGN: Patients undergoing gynecologic laparoscopy were
      randomly allocated to a control group (n=30), a 40 cmH2O PRM group (n=30), and a
      60 cmH2O PRM group (n=30). In the control group, residual carbon dioxide was
      removed by passive exsufflation through the port site. In the two intervention
      groups, the PRM consisting of five manual pulmonary inflations was performed at
      the end of surgery with a maximum pressure of 40 cmH2O or 60 cmH2O, respectively.
      Shoulder pain and wound pain were recorded using a visual analogue scale at 24
      and 48h postoperatively. RESULTS: Wound pain scores at 24 and 48h post-surgery
      were not different between the three groups. The PLSP scores in the two
      intervention groups were significantly lower than that seen in the control group
      at 24 and 48h postoperatively (P=0.006 and P<0.001, respectively). However, there
      were no statistically significant differences in the PLSP scores between the two
      intervention groups. CONCLUSION: A low-pressure PRM (40cmH2O) is as effective as
      a high-pressure PRM (60cmH2O) for removing residual gas from the peritoneal
      cavity. PRM using a maximal inspiratory pressure of 40cmH2O is safe and
      efficacious for the reduction of PLSP.

PMID- 27889666
TI  - YAP-dependent mechanotransduction is required for proliferation and migration on
      native-like substrate topography.
AB  - Native vascular extracellular matrices (vECM) consist of elastic fibers that
      impart varied topographical properties, yet most in vitro models designed to
      study the effects of topography on cell behavior are not representative of native
      architecture. Here, we engineer an electrospun elastin-like protein (ELP) system
      with independently tunable, vECM-mimetic topography and demonstrate that
      increasing topographical variation causes loss of endothelial cell-cell junction
      organization. This loss of VE-cadherin signaling and increased cytoskeletal
      contractility on more topographically varied ELP substrates in turn promote YAP
      activation and nuclear translocation, resulting in significantly increased
      endothelial cell migration and proliferation. Our findings identify YAP as a
      required signaling factor through which fibrous substrate topography influences
      cell behavior and highlights topography as a key design parameter for engineered
      biomaterials.

PMID- 27889669
TI  - Physicochemical analysis in the evaluation of reconstituted dry emulsion tablets.
AB  - The aim of this study was to characterize the formation of emulsions by droplet
      size analysis and turbidimetry during reconstitution from a solid dosage form,
      namely from dry emulsion systems, which carry an oil phase for poorly soluble
      active ingredients. For the dry emulsion systems tablets were prepared either
      from oil-in-water systems using a freeze-drying process or through direct
      compression containing the same oil and excipients. The ratios of oil to
      emulgents and oil to xanthan gum were equal in both methods. In the preparation
      methods applied, mannitol, erythritol and lactose were used as excipients and
      mannitol was found to be the most effective excipient based on droplet size
      reconstitution, turbidimetry and physical properties. Quality control involved
      testing the physical properties of tablets and characterizing the reconstituted
      emulsions.

PMID- 27889670
TI  - Selective recognition of cis-trans-isomers of platinum drugs and the detection of
      triplex DNA based on fluorescence reversible model of quantum dots.
AB  - The identification of spatial structures of drugs and the researches on their
      interaction mechanism with DNA are always attractive to the researchers. However,
      their realization is lack of simple and fast method. This paper reports the
      establishment of multiple-functional detection platform based on the "turn off
      on" model of ZnCdSe quantum dots. In this system, ZnCdSe quantum dots work as the
      fluorescent probe, platinum anti-cancer drugs as the quencher and triplex DNA as
      the trapping agent. The seemingly similar cisplatin and transplatin exhibited
      different fluorescent recovery behaviors due to their difference in structure,
      and thus realized the selective detection of cisplatin and transplatin with the
      reaction time set at 10min as well as the quantitation of cisplatin over the
      range of 2.5*10-8-100*10-8M. Based on this, the interactions between platinum
      anti-cancer drugs and ctDNA as well as polymorphic DNA were further studied, and
      realized the recognition of triplex DNA. The multiple-functional detection
      platform integrates the functions of the filtration of high-efficient platinum
      anti-cancer drugs, the researches on interaction mechanism of drugs, and the
      recognition of polymorphic DNA, meaningful to the future treatment of viral and
      cancers based on antisense gene strategy.

PMID- 27889671
TI  - European Journal of Cancer's Biennial report on soft tissue and visceral sarcomas
      or the rapid evolution of treatment concepts in sarcomas.
AB  - Soft tissue and visceral sarcoma gather a large group of rare to very rare
      cancers and locally aggressive connective tissue tumours. Novel concepts on
      histological and molecular classification, optimal management of patients,
      systemic adjuvant and neoadjuvant treatment have been emerging in the last 5
      years. In the present publication, we review and summarise significant changes
      which impact on disease management in this group of rare cancers.

PMID- 27889672
TI  - Spectroscopic investigation and direct comparison of the reactivities of iron
      pyridyl oxidation catalysts.
AB  - The growing interest in green chemistry has fueled attention to the development
      and characterization of effective iron complex oxidation catalysts. A number of
      iron complexes are known to catalyze the oxidation of organic substrates
      utilizing peroxides as the oxidant. Their development is complicated by a lack of
      direct comparison of the reactivities of the iron complexes. To begin to
      correlate reactivity with structural elements, we compare the reactivities of a
      series of iron pyridyl complexes toward a single dye substrate, malachite green
      (MG), for which colorless oxidation products are established. Complexes with
      tetradentate, nitrogen-based ligands with cis open coordination sites were found
      to be the most reactive. While some complexes reflect sensitivity to different
      peroxides, others are similarly reactive with either H2O2 or tBuOOH, which
      suggests some mechanistic distinctions. [Fe(S,S-PDP)(CH3CN)2](SbF6)2 and
      [Fe(OTf)2(tpa)] transition under the oxidative reaction conditions to a single
      intermediate at a rate that exceeds dye degradation (PDP=bis(pyridin-2-ylmethyl)
      bipyrrolidine; tpa=tris(2-pyridylmethyl)amine). For the less reactive
      [Fe(OTf)2(dpa)] (dpa=dipicolylamine), this reaction occurs on a timescale similar
      to that of MG oxidation. Thus, the spectroscopic method presented herein provides
      information about the efficiency and mechanism of iron catalyzed oxidation
      reactions as well as about potential oxidative catalyst decomposition and
      chemical changes of the catalyst before or during the oxidation reaction.

PMID- 27889673
TI  - Conformational equilibrium of phenylacetic acid and its halogenated analogues
      through theoretical studies, NMR and IR spectroscopy.
AB  - This paper presents a study on the conformational preferences of phenylacetic
      acid (PA) and its halogenated analogues (FPA, CPA, BPA). To clarify the effects
      that rule these molecules' behaviour, theoretical calculations were used, for
      both the isolated phase and solution, combined with nuclear magnetic resonance
      (NMR) and infrared (IR) spectroscopy. Most conformations of phenylacetic acid and
      its halogenated derivatives are stabilized through the hyperconjugative effect,
      which rules the conformational preference. NMR analyses showed that even with the
      variation in medium polarity, there was no significant change in the conformation
      population. Infrared spectroscopy showed similar results for all compounds under
      study. In most spectra, two bands were found through the carbonyl deconvolution,
      which is in accordance with the theoretical data. It was possible to prove that
      variation in the nature of the substituent in the ortho position had no
      significant influence on the conformational equilibrium.

PMID- 27889674
TI  - Design, synthesis, characterization and cation sensing behavior of amino
      naphthoquinone receptor: Selective colorimetric sensing of Cu(II) ion in nearly
      aqueous solution with mimicking logic gate operation.
AB  - An amino-naphthoquione receptor (R1) has been rationally designed, synthesized
      and characterized using 1H and 13C NMR, LCMS and single crystal X-ray diffraction
      studies. The receptor exhibits an instantaneous colour change from yellow to blue
      selectively with Cu(II) ions in water-DMF (98:2% v/v) medium. The results of UV
      Vis and fluorescence spectral studies indicates that the mechanism of sensing
      involves formation of a 1:1 complex between R1 and Cu(II) ion. The proposed
      mechanism has been confirmed through product analysis using FT-IR, UV-Vis, EPR
      and HRMS studies in addition to magnetic moment and elemental analysis
      measurements. The formed [Cu(R1)Cl2] possess a square planar geometry. The
      binding constant for the interaction of Cu(II) ion with the present unsubstituted
      quinone is found to be relatively higher than that with quinones containing
      electron withdrawing chlorine atom and electron releasing methyl group reported
      in literature. The detection limit of Cu(II) ion in aqueous solution by R1 is
      observed to be 8.7nM. The detection of Cu(II) ion by R1 in aqueous solution
      produces remarkable changes in the electronic and fluorescence spectra, which is
      applied to construct logic gate at molecular level.

PMID- 27889675
TI  - Solvatochromic fluorescence properties of phenothiazine-based dyes involving
      thiazolo[4,5-b]quinoxaline and benzo[e]indole as strong acceptors.
AB  - The present work describes the photophysical properties of two newly synthesized
      compounds, namely (E)-10-butyl-3-(2-(thiazolo[4,5-b]quinoxalin-2-yl)vinyl)-10H
      phenothiazine (PTQ) and (E)-10-butyl-3-(2-(1,1-dimethyl-1H-benzo[e]indol-2
      yl)vinyl)-10H-phenothiazine (PBI). A strong intramolecular charge transfer (ICT)
      is observed in both dyes as indicated from absorption and emission studies on
      varying the solvent polarity. This can be concluded from the large Stokes shifts
      among these dyes as PTQ exhibits large Stokes shift with >270nm and PBI around
      200nm. The effect of increasing polarity caused drastic increase in the charge
      transfer process leading to twisted intramolecular charge transfer (TICT) process
      in both the dyes PTQ and PBI. Time-resolved emission studies and non-radiative
      decay rate constant indicates that the excited states of both dyes behave
      differently with respect to solvent polarity. The non-radiative decay constant
      increases dramatically with the solvent polarity specifying change of ICT
      emissive states in non-polar solvent while TICT emitting states in highly polar
      solvent. On the other hand, PBI follows a general trend initially exhibiting
      higher non-radiative decay constant in non-polar solvent like cyclohexane, lowest
      in moderate polarity owing to the ICT emissive state but with increase in the
      polarity, the non-radiative decay constant again increases indicating TICT
      states.

PMID- 27889676
TI  - Towards a threshold climate for emergency lower respiratory hospital admissions.
AB  - Identification of 'cut-points' or thresholds of climate factors would play a
      crucial role in alerting risks of climate change and providing guidance to
      policymakers. This study investigated a 'Climate Threshold' for emergency
      hospital admissions of chronic lower respiratory diseases by using a distributed
      lag non-linear model (DLNM). We analysed a unique longitudinal dataset (10 years,
      2000-2009) on emergency hospital admissions, climate, and pollution factors for
      the Greater London. Our study extends existing work on this topic by considering
      non-linearity, lag effects between climate factors and disease exposure within
      the DLNM model considering B-spline as smoothing technique. The final model also
      considered natural cubic splines of time since exposure and 'day of the week' as
      confounding factors. The results of DLNM indicated a significant improvement in
      model fitting compared to a typical GLM model. The final model identified the
      thresholds of several climate factors including: high temperature (>=27 degrees
      C), low relative humidity (<= 40%), high Pm10 level (>=70-ug/m3), low wind speed
      (<= 2 knots) and high rainfall (>=30mm). Beyond the threshold values, a
      significantly higher number of emergency admissions due to lower respiratory
      problems would be expected within the following 2-3 days after the climate shift
      in the Greater London. The approach will be useful to initiate 'region and
      disease specific' climate mitigation plans. It will help identify spatial hot
      spots and the most sensitive areas and population due to climate change, and will
      eventually lead towards a diversified health warning system tailored to specific
      climate zones and populations.

PMID- 27889678
TI  - Early hippocampal hyperexcitability in PS2APP mice: role of mutant PS2 and APP.
AB  - Alterations of brain network activity are observable in Alzheimer's disease (AD)
      together with the occurrence of mild cognitive impairment, before overt
      pathology. However, in humans as well in AD mouse models, identification of early
      biomarkers of network dysfunction is still at its beginning. We performed in vivo
      recordings of local field potential activity in the dentate gyrus of PS2APP mice
      expressing the human amyloid precursor protein (APP) Swedish mutation and the
      presenilin-2 (PS2) N141I. From a frequency-domain analysis, we uncovered network
      hyper-synchronicity as early as 3 months, when intracellular accumulation of
      amyloid beta was also observable. In addition, at 6 months of age, we identified
      network hyperactivity in the beta/gamma frequency bands, along with increased
      theta-beta and theta-gamma phase-amplitude cross-frequency coupling, in
      coincidence with the histopathological traits of the disease. Although
      hyperactivity and hypersynchronicity were respectively detected in mice
      expressing the PS2-N141I or the APP Swedish mutant alone, the increase in cross
      frequency coupling specifically characterized the 6-month-old PS2APP mice, just
      before the surge of the cognitive decline.

PMID- 27889677
TI  - Blood DNA methylation age is not associated with cognitive functioning in middle
      aged monozygotic twins.
AB  - The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age
      related changes of DNA methylation at multiple sites of the genome and is
      suggested to be a biomarker for biological age. Elevated blood DNAmAge is
      associated with all-cause mortality, with the strongest effects reported in a
      recent intrapair twin study where epigenetically older twins had increased
      mortality risk in comparison to their co-twins. In the study presented here, we
      hypothesize that DNAmAge in blood is associated with cross-sectional and
      longitudinal cognitive abilities in middle-aged individuals. In 486 monozygotic
      twins, we investigated the association of DNAmAge, difference between DNAmAge and
      chronological age and age acceleration with cognition. Despite using a powerful
      paired twin design, we found no evidence for association of blood DNAmAge with
      cognitive abilities. This observation was confirmed in unpaired analyses, where
      DNAmAge initially correlated with cognitive abilities, until adjusting for
      chronological age. Overall, our study shows that for middle-aged individuals
      DNAmAge calculated in blood does not correlate with cognitive abilities.

PMID- 27889679
TI  - Radiographic assessment of the postoperative knee.
AB  - Radiologists often encounter postoperative knee radiographs lacking any adjunct
      clinical data which might hinder accurate image interpretation. Surgical
      techniques are constantly evolving with new devices being used which make it
      sometimes challenging for the radiologist to deduce the performed procedure and
      to look for associated complications. This article reviews commonly performed
      surgical procedures of the knee, highlights their expected postoperative
      radiographic appearance and describes the appearance of certain postoperative
      complications.

PMID- 27889681
TI  - Change over time in women's views and experiences of maternity care in England,
      1995-2014: A comparison using survey data.
AB  - BACKGROUND: there have been changes in maternity care policy over the last 20
      years and women's experience, continuity and satisfaction with care have become
      more prominent. However there has been no research examining changes over time in
      women's reported experience. METHODS: this study used secondary analysis of data
      collected in four postal surveys of maternity care experiences in 1995, 2006,
      2010 and 2014. In each case women who had delivered in a specified time period in
      England were randomly sampled and sent a questionnaire three months after the
      birth. Women were excluded if they were aged less than 16 years or their infant
      had died. The majority of questions were comparable over the different surveys.
      Descriptive statistics and adjusted odds ratios are presented. FINDINGS: in the
      antenatal period, an increasing proportion of women had early first contact with
      a healthcare professional, screening for Down's syndrome, both dating and anomaly
      scans and the total number of ultrasound scans increased over the period. The
      proportion of women given explanations about screening and choice regarding
      interventions during labour and birth both appear to have increased. In the
      postnatal period, length of hospital stay declined over time but the proportion
      of women who considered their length of stay too short remained constant. The
      number of postnatal home visits also declined and there was a substantial
      increase in the proportion of women who would have liked more visits. Overall
      satisfaction with care remained high especially for care during pregnancy, labour
      and birth. CONCLUSIONS: despite fewer antenatal checks, shorter hospital stays
      and fewer postnatal home visits, women were generally very positive about their
      care in pregnancy, labour and birth, and the postnatal period. Maternity care has
      changed in many respects, with earlier contact with health professionals, more
      scans and more information. However, reduced continuity of care and a need for
      support in the early weeks with a new infant was expressed by many women and are
      issues that may be contributing to some of the dissatisfaction expressed.

PMID- 27889680
TI  - Development and measurement properties of the Chinese breastfeeding self
      regulation questionnaire.
AB  - BACKGROUND: although new mothers are aware of the benefits of breastfeeding, many
      of them stop breastfeeding early in the postpartum period. Maternal psychosocial
      factors have been shown to contribute to early breastfeeding cessation. According
      to Self-Determination Theory (SDT) maternal self-determination is an
      indispensable factor in studying motivation to breastfeed. There are no validated
      instruments to assess maternal breastfeeding motivation and self-determination.
      OBJECTIVE: our aim was to develop and assess the psychometric properties of the
      Breastfeeding Self -Regulation Questionnaire (BSRQ) for Chinese pregnant women in
      Hong Kong. METHOD: we reviewed the literature and devised items for a preliminary
      version of the questionnaire. Thirty-five context-specific items in English were
      generated. We translated the items into Chinese and then back translated them
      into English following established translation procedures. We employed
      exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to
      assess the structure of the questionnaire. Predictive validity was measured by
      assessing the relationship between the BRSQ score and actual duration of
      breastfeeding. FINDINGS: we recruited 591 participants from three publicly funded
      antenatal clinics. Of the 35 items in the preliminary BSRQ, 22 were retained by
      EFA. CFA revealed that there were 5 factors including intrinsic, identified,
      integrated, introjected and external regulation. The goodness of fit of the CFA
      model was adequate. The Cronbach's alpha of the BSRQ was 0.86. For every one
      point increase in the BSRQ score, participants had 15% higher odds of any
      breastfeeding (OR=1.15, 95%CI 1.07-1.23) and 9% higher odds of exclusive
      breastfeeding (OR=1.09, 95%CI 1.02-1.17) at 6 weeks postpartum. CONCLUSION: the
      Chinese version of the BSRQ was a valid and reliable tool to measure maternal
      self-determination towards breastfeeding.

PMID- 27889682
TI  - 'Stress, anger, fear and injustice': An international qualitative survey of
      women's experiences planning a vaginal breech birth.
AB  - OBJECTIVE: the outcomes of the Term Breech Trial had a profound impact on women's
      options for breech birth, with caesarean section now seen as the default method
      for managing breech birth by many clinicians. Despite this, the demand for
      planned vaginal breech birth from women does exist. This study aimed to examine
      the experiences of women who sought a vaginal breech birth to increase
      understanding as to how to care for women seeking this birth option. DESIGN: an
      electronic survey was distributed to women online via social media. The survey
      consisted of qualitative and quantitative questions, with the qualitative data
      being the focus of this paper. Open ended questions sought information on the
      ways in which woman sourced a clinician skilled in vaginal breech birth and the
      level of support and quality of information provided from clinicians regarding
      vaginal breech birth. Thematic analysis was used to analyse and code the
      qualitative data into major themes. FINDINGS: in total, 204 women from over seven
      countries responded to the survey. Written responses to the open ended questions
      were categorised into seven themes: Seeking the chance to try for a VBB;
      Encountering coercion and fear; Putting the birth before the baby?; Dealing with
      emotional wounds; Searching for information and support; Traveling across
      boundaries; Overcoming obstacles in the system. KEY CONCLUSIONS: for women
      seeking vaginal breech birth, limited system and clinical support can impede
      access to balanced information and options for care. Recognition of existing
      evidence on the safety of vaginal breech birth, as well as the presence of
      clinical guidelines that support it, may assist in promoting vaginal breech birth
      as a legitimate option that should be available to women.

PMID- 27889683
TI  - Biomechanics of simulated versus natural cross-country sit skiing.
AB  - The purpose of this study was to investigate the biomechanics of cross-country
      sit-skiing in simulated and natural skiing. Thirteen international level athletes
      participated in a ski ergometer test (simulated conditions) and a test on snow in
      a ski-tunnel (natural conditions) using their personal sit-ski. Tests in both
      conditions were performed at individual maximal speed. When comparing the two
      conditions the main results were: (1) maximal speed in simulated conditions was
      lower (p<0.05) but correlated well with the natural condition (r=0.79, p<0.001);
      (2) no differences in pole force variables were found; peak force (r=0.77,
      p<0.01) and average force (r=0.78, p<0.01) correlated well; (3) recovery time and
      time to peak did not differ and time to impact correlated with each other
      (r=0.88, p<0.01); (4) no differences were found in peak electromyography (EMG)
      and average EMG for Triceps, Pectoralis, and Erector Spinae; Rectus Abdominis did
      not differ in peak. EMG peak and average EMG of all muscles were correlated
      between the two conditions (r=0.65-0.94; p<0.05-0.01). Although some differences
      were observed, this study demonstrated that technical skill proficiency in
      natural and simulated cross-country skiing is comparable from a force production
      and muscle activation perspective.

PMID- 27889684
TI  - Human milk oligosaccharide effects on intestinal function and inflammation after
      preterm birth in pigs.
AB  - : Human milk oligosaccharides (HMOs) may mediate prebiotic and anti-inflammatory
      effects in newborns. This is particularly important for preterm infants who are
      highly susceptible to intestinal dysfunction and necrotizing enterocolitis (NEC).
      We hypothesized that HMO supplementation of infant formula (IF) improves
      intestinal function, bacterial colonization and NEC resistance immediately after
      preterm birth, as tested in a preterm pig model. Mixtures of HMOs were
      investigated in intestinal epithelial cells and in preterm pigs (n=112) fed IF
      supplemented without (CON) or with a mixture of four HMOs (4-HMO) or >25 HMOs (25
      HMO, 5-10 g/L given for 5 or 11 days). The 25-HMO blend decreased cell
      proliferation and both HMO blends decreased lipopolysaccharide-induced
      interleukin-8 secretion in IPEC-J2 cells, relative to control (P<.05). All HMOs
      were found in urine and feces of HMO-treated pigs, and short-chain fatty acids in
      the colon were higher in HMO vs. CON pigs (P<.05). After 5 days, NEC lesions were
      similar between HMO and CON pigs and 25-HMO increased colon weights (P<.01).
      After 11 days, the 4-HMO diet did not affect NEC (56 vs. 79%, P=.2) but increased
      dehydration and diarrhea (P<.05) and expression of immune-related genes (IL10,
      IL12, TGFbeta, TLR4; P<.05). Bacterial adherence and diversity was unchanged
      after HMO supplementation. CONCLUSION: Complex HMO-blends affect intestinal
      epithelial cells in vitro and gut gene expression and fermentation in preterm
      pigs. However, the HMOs had limited effects on NEC and diarrhea when supplemented
      to IF. Longer-term exposure to HMOs may be required to improve the immature
      intestinal function in formula-fed preterm neonates.

PMID- 27889685
TI  - A naturally occurring mixture of tocotrienols inhibits the growth of human
      prostate tumor, associated with epigenetic modifications of cyclin-dependent
      kinase inhibitors p21 and p27.
AB  - Tocotrienols, members of the vitamin E family, have three unsaturated bonds in
      their side chains. Recently, it has been suggested that the biological effects of
      tocotrienols may differ from that of tocopherols. Several in vitro studies have
      shown that tocotrienols have stronger anticancer effects than tocopherols. VCaP
      cell line used in this study is from a vertebral bone metastasis from a patient
      with prostate cancer. Eight-week-old male NCr(-/-) nude mice were subcutaneously
      injected with VCaP-luc cells in matrigel and then administered a tocotrienol
      mixture for 8 weeks. The tocotrienol mixture inhibited the growth of human
      prostate tumor xenografts in a dose-dependent manner. The concentrations of
      tocotrienols and their metabolites were significantly increased in treatment
      groups. Tocotrienols inhibited prostate tumor growth by suppressing cell
      proliferation, which was associated with the induction of the cyclin-dependent
      kinase (CDK) inhibitors p21 and p27. In addition, tocotrienol treatment was
      associated with elevated H3K9 acetylation levels at proximal promoter regions of
      p21 and p27 and with decreased expression of histone deacetylases. Tocotrienols
      inhibited human prostate tumor growth, associated with up-regulation of the CDK
      inhibitors p21 and p27. Elevated expression of p21 and p27 could be partly due to
      the suppressed expression of HDACs.

PMID- 27889687
TI  - Role of inflammation in obesity-related breast cancer.
AB  - Chronic inflammation associated with obesity is now recognized to be an important
      condition in promoting carcinogenesis and progression in breast cancer patients,
      mostly in postmenopausal women with tumors expressing estrogen and progesterone
      receptors. In obese patients, altered levels of several inflammatory mediators
      regulating aromatase and estrogen expression are one of the mechanisms
      responsible of increase breast cancer risk. Growing attention has also been paid
      to the local adipose inflammation and the role played by macrophages as
      determinants of breast cancer risk recurrence and prognosis. The inflammation
      obesity axis offers different molecular signaling pathways for therapeutic
      interventions and potential pharmacological targets. The increasing rate of
      obesity worldwide associated with the recent findings linking inflammation and
      breast cancer urge further investigation.

PMID- 27889686
TI  - MicroRNA-181 contributes to downregulation of SAMHD1 expression in CD4+ T-cells
      derived from Sezary syndrome patients.
AB  - Sezary syndrome (SS) is a rare subtype of cutaneous T-cell lymphoma (CTCL) that
      is characterized by aggressive spread of neoplastic CD4+ T-cells from the skin
      into the bloodstream with metastasis to visceral organs. The deoxynucleoside
      triphosphohydrolase SAMHD1 is highly expressed in normal CD4+ T-cells, while its
      expression is down-regulated in CD4+ T-cells from SS patients. MicroRNA (miR)
      dysregulation is an important epigenetic mechanism in the pathogenesis and
      progression of SS. MiR-181 has been shown to inhibit SAMHD1 expression in cell
      lines and was identified as an important prognostic biomarker in CTCL. However,
      whether SAMHD1 is down-regulated by miR-181 in primary CD4+ T-cells of SS
      patients is unknown. Compared to normal CD4+ T-cells, SAMHD1 protein expression
      is significantly reduced in transformed CD4+ T-cell lines and CD4+ T-cells from
      SS patients, which inversely correlates with increased miR-181 levels in these
      cells. Over-expression of miR-181b in primary CD4+ T-cells from healthy donors
      significantly decreased SAMHD1 protein level, but not mRNA level. In contrast,
      inhibition of miR-181 in a CD4+ T-cell line significantly increased the level of
      SAMHD1 protein expression. Our results demonstrate that miR-181 is an important
      regulator of SAMHD1 protein expression in neoplastic CD4+ T-cells, likely through
      a mechanism of translational inhibition.

PMID- 27889688
TI  - Management of distal deep vein thrombosis.
AB  - Isolated distal deep vein thrombosis (DVT), also known as calf DVT, represents up
      to 50% of all lower limb DVT in ultrasound series and is therefore a frequent
      medical condition. Unlike proximal DVT and pulmonary embolism (PE), which have
      been extensively studied and for which management is well standardized, much less
      is known on the optimal management of isolated calf DVT. Recent data arising from
      registries and non-randomized studies suggest that most distal DVTs do not extend
      to the proximal veins and have an uneventful follow-up when left untreated. This
      data had some impact on the international recommendations which recently stated
      that ultrasound surveillance instead of systematic therapeutic anticoagulation
      might be an option for selected low-risk patients. However, robust data arising
      from randomized studies are scarce. Indeed, only five randomized trials assessing
      the need for anticoagulation for calf DVT have been published. Many of these
      trials had an open-label design and were affected by methodological limitations.
      The only randomized placebo-controlled trial included low-risk patients
      (outpatients without cancer or previous venous thromboembolic events (VTE)) and
      was hampered by a limited statistical power. Nevertheless, data from this trial
      tend to confirm that the use of therapeutic anticoagulation in low-risk patients
      with symptomatic calf DVT is not superior to placebo in reducing VTE, but is
      associated with a significantly higher risk of bleeding. Further randomized
      studies are needed to define the best therapy for high-risk patients (inpatients,
      patients with active cancer or previous VTE), and the optimal dose and duration
      of treatment.

PMID- 27889689
TI  - Osteoarthritis and type 2 diabetes mellitus: What are the links?
AB  - Osteoarthritis (OA) is the most frequent joint disorder and one of the leading
      cause of disability. During a long time, it was considered as the consequence of
      aging and mechanical stress on cartilage. Recent advances in the knowledge of OA
      have highlighted that it is a whole joint disease with early modifications of
      synovium and subchondral bone but also that it is associated with obesity and
      metabolic syndrome through systemic mechanisms. In the past year, type 2 diabetes
      has been described in two meta-analyzes as an independent risk factor for OA. In
      vivo models of diabetes corroborated epidemiological studies. Indeed, diabetic
      rodents display a spontaneous and a more severe experimental OA than their non
      diabetic counterparts, which can be partially prevented by diabetes treatment
      (insulin, pioglitazone). The negative impact of diabetes on joints could be
      explain by the induction of oxidative stress and pro-inflammatory cytokines but
      also by advanced age products accumulation in joint tissues exposed to chronic
      high glucose concentration. Insulin resistance might also impair joint tissue
      because of a local insulin resistance of diabetic synovial membrane but also by
      the systemic low grade inflammation state related to obesity and insulin
      resistant state.

PMID- 27889690
TI  - Sex differences in insulin sensitivity and insulin response with increasing age
      in black South African men and women.
AB  - AIMS: Black Africans are disproportionally affected by type 2 diabetes, but the
      pathophysiology is poorly understood. The study aimed to examine the effect of
      sex and age on insulin sensitivity and insulin response in black South African
      adults. METHODS: This cross-sectional study included a random sample of 179 men
      and 260 women aged 25-74years with normal glucose tolerance from 5 peri-urban
      townships in Cape Town, SA. Insulin sensitivity (insulin sensitivity index,
      ISI0,120) and response (insulinogenic index, IGI), and the disposition index (DI,
      ISI0,120*IGI), derived from an oral glucose tolerance test, were measured.
      RESULTS: Although men were older (median [interquartile range]: 39 [30-48] vs. 35
      [29-44], P=0.021) and had significantly lower BMI than women (22.6 [20.0-25.3]
      vs. 31.0 [25.9-35.7] kg/m2, P=0.001), DI was not different (P=0.740), but
      ISI0,120 was higher (P=0.007) and IGI was lower (P=0.074) in men than women,
      adjusting for age and BMI. With increasing age, DI (beta (95%CI): -24.4 (-36.3 to
      -12.5), P<0.001) and IGI (beta (95%CI): -4.9 (-7.5 to -2.2), P<0.001) decreased
      similarly in both sexes, but ISI0,120 did not change (beta (95%CI): 0.005 (-0.20
      to 0.03), P=0.675). CONCLUSION: Black South African women with normal glucose
      tolerance have lower insulin sensitivity than their male counterparts, but
      increase their insulin response to maintain normoglycemia. With increasing age,
      insulin sensitivity remains unchanged, but the insulin response decreases at a
      similar rate in men and women.

PMID- 27889692
TI  - Corrigendum.

PMID- 27889691
TI  - Development of a Culturally Competent Service to Improve Academic Functioning for
      Latino Survivors of Acute Lymphoblastic Leukemia: Methodological Considerations.
AB  - Many survivors of childhood acute lymphoblastic leukemia (ALL) develop
      neurocognitive deficits that compromise academic functioning, especially in the
      presence of sociodemographic risk factors. The extent to which these risk factors
      coexist for Latino ALL survivors is not well described, but with shifts in U.S.
      demographics and improved survival in ALL, culturally competent interventions are
      needed. The Achieving Best Cognitive Successes after Cancer service was designed
      and implemented by a team representing nursing, medicine, psychology, and social
      work. Service components include neurocognitve assessment and individualized
      intervention for treatment-related risks and improving academic success for
      school-aged ALL survivors. Interventions are child-focused and parent-directed,
      recognizing that parents are major sources of support and advocates for their
      children within school systems. The service was designed to be culturally
      appropriate for the predominantly Latino patient population at our center, based
      on (1) linguistic competency of children and parents; (2) multicultural and
      ecological considerations for urban, low socioeconomic status, and migrant
      populations; (3) literacy barriers; and (4) contextual factors. This report
      describes methodological considerations and practice implications relevant to the
      design and implementation of similar culturally competent services for Latino
      pediatric cancer survivors.

PMID- 27889693
TI  - Health inequalities: critical perspectives.

PMID- 27889696
TI  - A Message from the Editor-in-Chief.

PMID- 27889697
TI  - Characterization of plastic blends made from mixed plastics waste of different
      sources.
AB  - This paper studies the recyclability of construction and household plastic waste
      collected from local landfills. Samples were processed from mixed plastic waste
      by injection moulding. In addition, blends of pure plastics, polypropylene and
      polyethylene were processed as a reference set. Reference samples with known
      plastic ratio were used as the calibration set for quantitative analysis of
      plastic fractions in recycled blends. The samples were tested for the tensile
      properties; scanning electron microscope-energy-dispersive X-ray spectroscopy was
      used for elemental analysis of the blend surfaces and Fourier transform infrared
      (FTIR) analysis was used for the quantification of plastics contents.

PMID- 27889699
TI  - Comparison of Clinical Factors Between Patients With Angiotensin-Converting
      Enzyme Inhibitor-Induced Angioedema and Cough.
AB  - BACKGROUND: Angioedema is a rare and serious adverse drug reaction (ADR) to
      angiotensin-converting enzyme (ACE) inhibitor treatment. Dry cough is a common
      side effect of ACE inhibitors and has been identified as a possible risk factor
      for angioedema. OBJECTIVE: We compared characteristics between patients with ACE
      inhibitor-induced angioedema and cough with the aim of identifying risk factors
      that differ between these adverse events. METHODS: Data on patients with
      angioedema or cough induced by ACE inhibitors were collected from the Swedish
      database of spontaneously reported ADRs or from collaborating clinicians.
      Wilcoxon rank sum test, Fisher's exact test, and odds ratios (ORs) with 95% CIs
      were used to test for between-group differences. The significance threshold was
      set to P <0.00128 to correct for multiple comparisons. RESULTS: Clinical
      characteristics were compared between 168 patients with angioedema and 121 with
      cough only. Smoking and concomitant selective calcium channel blocker treatment
      were more frequent among patients with angioedema than cough: OR = 4.3, 95% CI =
      2.1-8.9, P = 2.2 * 10-5, and OR = 3.7, 95% CI = 2.0-7.0, P = 1.7 * 10-5.
      Angioedema cases were seen more often in male patients (OR = 2.2, 95% CI = 1.4
      3.6, P = 1.3 * 10-4) and had longer time to onset and higher doses than those
      with cough ( P = 3.2 * 10-10 and P = 2.6 * 10-4). A multiple model containing the
      variables smoking, concurrent calcium channel blocker treatment, male sex, and
      time to onset accounted for 26% of the variance between the groups. CONCLUSION:
      Smoking, comedication with selective calcium channel blockers, male sex, and
      longer treatment time were associated with ACE inhibitor-induced angioedema
      rather than cough.

PMID- 27889700
TI  - Clarence Borel.
AB  - Borel v. Fibreboard Paper Products Corporation is the 1973 landmark case that
      paved the way for successful litigation against the asbestos industry. Clarence
      Borel's granddaughter shares recollections of the reluctant man behind the court
      case.

PMID- 27889701
TI  - Publishing interim results of randomised clinical trials in peer-reviewed
      journals.
AB  - BACKGROUND: Interim analyses of randomised controlled trials are sometimes
      published before the final results are available. In several cases, the treatment
      effects were noticeably different after patient recruitment and follow-up
      completed. We therefore conducted a literature review of peer-reviewed journals
      to compare the reported treatment effects between interim and final publications
      and to examine the magnitude of the difference. METHODS: We performed an
      electronic search of MEDLINE from 1990 to 2014 (keywords: 'clinical trial' OR
      'clinical study' AND 'random*' AND 'interim' OR 'preliminary'), and we manually
      identified the corresponding final publication. Where the electronic search
      produced a final report in which the abstract cited interim results, we found the
      interim publication. We also manually searched every randomised controlled trial
      in eight journals, covering a range of impact factors and general medical and
      specialist publications (1996-2014). All paired articles were checked to ensure
      that the same comparison between interventions was available in both. RESULTS: In
      all, 63 studies are included in our review, and the same quantitative comparison
      was available in 58 of these. The final treatment effects were smaller than the
      interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There
      was a marked reduction, defined as a >=20% decrease in the size of the treatment
      effect from interim to final analysis, in 11 (19%) trials compared to a marked
      increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in
      trials where commercial support was reported, and increased as the proportion of
      final events at the interim report decreased in trials where commercial support
      was reported (interaction p = 0.023). There was no evidence of a difference
      between trials that stopped recruitment at the interim analysis where this was
      reported as being pre-specified versus those that were not pre-specified
      (interaction p = 0.87). CONCLUSION: Published interim trial results were more
      likely to be associated with larger treatment effects than those based on the
      final report. Publishing interim results should be discouraged, in order to have
      reliable estimates of treatment effects for clinical decision-making, regulatory
      authority reviews and health economic analyses. Our work should be expanded to
      include conference publications and manual searches of additional journal
      publications.

PMID- 27889702
TI  - Statins and the cholesterol mortality paradox.
AB  - Large-scale randomised controlled trials, carried out in the context of secondary
      cardiovascular prevention, have shown that statins are superior to placebo: these
      drugs were shown to decrease cardiovascular events and total mortality. A further
      set of clinical trials compared high intensity to low/standard intensity LDL
      cholesterol lowering in the same setting (using either statins or a
      statin/ezetimibe association). In this case, a decrease in LDL cholesterol and a
      concomitant significant reduction in cardiovascular events were seen with
      intensive therapy, however with no change in total mortality. This phenomenon we
      may term the LDL cholesterol mortality paradox. It could be due either to the
      prevention (by high-intensity therapy) of episodes not severe enough to lead to
      the death of patients, or to high-intensity therapy leading to the death of some
      patients at the same time as preventing the death of others, with a null
      aggregate effect. Several types of adverse effects have been seen with statin
      therapy, such as a possible increased incidence of Diabetes mellitus and of
      myopathy. The decision to start high-intensity LDL cholesterol lowering (rather
      than low- or moderate-intensity statin treatment) should be evaluated on a case
      by-case basis, taking into consideration the overall aspects of each patient,
      including the patient's preferences. High-intensity LDL cholesterol lowering, up
      to the present moment, has failed to produce a change in overall prognosis (total
      mortality), and should not therefore be mandatory in secondary cardiovascular
      prevention. It remains to be seen if a similar LDL cholesterol mortality paradox
      occurs with new drugs targeting plasma lipids.

PMID- 27889703
TI  - The Santorini Conferences continue.

PMID- 27889704
TI  - Pharmacogenetic studies: a tool to improve antidepressant therapy.
AB  - The World Health Organization (WHO) predicts that major depressive disorder (MDD)
      will be the second leading cause of death and disability by 2020. Nowadays,
      approximately 60-70% of patients with this disorder have shown the lack of
      effectiveness and tolerability of the therapy with antidepressants. The US Food
      and Drug Administration (FDA) and the European Medicine Agency (EMA) are
      including pharmacogenetic information in the labeling of several antidepressants.
      The presence of this information represents the relevance of genetic
      polymorphisms in drug response. These pharmacogenetic studies have been based on
      the knowledge of genes involved in pharmacokinetic (CYP2D6, CYP2C19 and ABCB1)
      and pharmacodynamic (SLC6A4, HTR2A, BDNF, GNB3 and FKBP5) processes of
      antidepressant medications. The knowledge of the genotype of patients with MDD is
      an important tool for personalized therapy that can improve their clinical
      response to treatment. In this review, we highlight the most relevant genes
      involved in the metabolism of antidepressants (ADs) or the genes related to the
      presence of adverse reactions.

PMID- 27889705
TI  - Effect Estimation in Point-Exposure Studies with Binary Outcomes and High
      Dimensional Covariate Data - A Comparison of Targeted Maximum Likelihood
      Estimation and Inverse Probability of Treatment Weighting.
AB  - Inverse probability of treatment weighting (IPW) and targeted maximum likelihood
      estimation (TMLE) are relatively new methods proposed for estimating marginal
      causal effects. TMLE is doubly robust, yielding consistent estimators even under
      misspecification of either the treatment or the outcome model. While IPW methods
      are known to be sensitive to near violations of the practical positivity
      assumption (e. g., in the case of data sparsity), the consequences of this
      violation in the TMLE framework for binary outcomes have been less widely
      investigated. As near practical positivity violations are particularly likely in
      high-dimensional covariate settings, a better understanding of the performance of
      TMLE is of particular interest for pharmcoepidemiological studies using large
      databases. Using plasmode and Monte-Carlo simulation studies, we evaluated the
      performance of TMLE compared to that of IPW estimators based on a point-exposure
      cohort study of the marginal causal effect of post-myocardial infarction statin
      use on the 1-year risk of all-cause mortality from the Clinical Practice Research
      Datalink. A variety of treatment model specifications were considered, inducing
      different degrees of near practical non-positivity. Our simulation study showed
      that the performance of the TMLE and IPW estimators were comparable when the
      dimension of the fitted treatment model was small to moderate; however, they
      differed when a large number of covariates was considered. When a rich outcome
      model was included in the TMLE, estimators were unbiased. In some cases, we found
      irregular bias and large standard errors with both methods even with a correctly
      specified high-dimensional treatment model. The IPW estimator showed a slightly
      better root MSE with high-dimensional treatment model specifications in our
      simulation setting. In conclusion, for estimation of the marginal expectation of
      the outcome under a fixed treatment, TMLE and IPW estimators employing the same
      treatment model specification may perform differently due to differential
      sensitivity to practical positivity violations; however, TMLE, being doubly
      robust, shows improved performance with richer specifications of the outcome
      model. Although TMLE is appealing for its double robustness property, such
      violations in a high-dimensional covariate setting are problematic for both
      methods.

PMID- 27889706
TI  - Using Relative Statistics and Approximate Disease Prevalence to Compare Screening
      Tests.
AB  - Schatzkin et al. and other authors demonstrated that the ratios of some
      conditional statistics such as the true positive fraction are equal to the ratios
      of unconditional statistics, such as disease detection rates, and therefore we
      can calculate these ratios between two screening tests on the same population
      even if negative test patients are not followed with a reference procedure and
      the true and false negative rates are unknown. We demonstrate that this same
      property applies to an expected utility metric. We also demonstrate that while
      simple estimates of relative specificities and relative areas under ROC curves
      (AUC) do depend on the unknown negative rates, we can write these ratios in terms
      of disease prevalence, and the dependence of these ratios on a posited prevalence
      is often weak particularly if that prevalence is small or the performance of the
      two screening tests is similar. Therefore we can estimate relative specificity or
      AUC with little loss of accuracy, if we use an approximate value of disease
      prevalence.

PMID- 27889698
TI  - Major involvement of bacterial components in rheumatoid arthritis and its
      accompanying oxidative stress, systemic inflammation and hypercoagulability.
AB  - We review the evidence that infectious agents, including those that become
      dormant within the host, have a major role to play in much of the etiology of
      rheumatoid arthritis and the inflammation that is its hallmark. This occurs in
      particular because they can produce cross-reactive (auto-)antigens, as well as
      potent inflammagens such as lipopolysaccharide that can themselves catalyze
      further inflammagenesis, including via beta-amyloid formation. A series of
      observables coexist in many chronic, inflammatory diseases as well as rheumatoid
      arthritis. They include iron dysregulation, hypercoagulability, anomalous
      morphologies of host erythrocytes, and microparticle formation. Iron
      dysregulation may be responsible for the periodic regrowth and resuscitation of
      the dormant bacteria, with concomitant inflammagen production. The present
      systems biology analysis benefits from the philosophical idea of "coherence,"
      that reflects the principle that if a series of ostensibly unrelated findings are
      brought together into a self-consistent narrative, that narrative is thereby
      strengthened. As such, we provide a coherent and testable narrative for the major
      involvement of (often dormant) bacteria in rheumatoid arthritis.

PMID- 27889707
TI  - Transgenerational programming of longevity through E(z)-mediated histone H3K27
      trimethylation in Drosophila.
AB  - Transgenerational effects on health and development of early-life nutrition have
      gained increased attention recently. However, the underlying mechanisms of
      transgenerational transmission are only starting to emerge, with epigenetics as
      perhaps the most important mechanism. We recently reported the first animal model
      to study transgenerational programming of longevity after early-life dietary
      manipulations, enabling investigations to identify underlying epigenetic
      mechanisms. We report here that post-eclosion dietary manipulation (PDM) with a
      low-protein (LP) diet upregulates the protein level of E(z), an H3K27 specific
      methyltransferase, leading to higher levels of H3K27 trimethylation (H3K27me3).
      This PDM-mediated change in H3K27me3 corresponded with a shortened longevity of
      F0 flies as well as their F2 offspring. Specific RNAi-mediated post-eclosion
      knockdown of E(z) or pharmacological inhibition of its enzymatic function with
      EPZ-6438 in the F0 parents improved longevity while rendering H3K27me3 low across
      generations. Importantly, addition of EPZ-6438 to the LP diet fully alleviated
      the longevity-reducing effect of the LP PDM, supporting the increased level of
      E(z)-dependent H3K27me3 as the primary cause and immediate early-life period as
      the critical time to program longevity through epigenetic regulation. These
      observations establish E(z)-mediated H3K27me3 as one epigenetic mechanism
      underlying nutritional programming of longevity and support the use of EPZ-6438
      to extend lifespan.

PMID- 27889709
TI  - Role of Mid-induction Peripheral Blood Minimal Residual Disease Detection in
      Pediatric B-Lineage Acute Lymphoblastic Leukemia.
AB  - OBJECTIVE: To study the role of mid-induction (day 15) peripheral blood minimal
      residual disease (PB-MRD) detection in pediatric B- lineage acute lymphoblastic
      leukemia (B-ALL). DESIGN: Prospective. SETTING: Tertiary-care center. PATIENTS:
      40 consecutively-diagnosed treatment-naive, pediatric B-ALL patients.
      INTERVENTION: National Cancer Institute (NCI) standard risk patients were given
      three drug induction regimen comprising vincristine, L-asparginase and
      prednisolone; NCI high-risk patients were supplemented with daunorubicin. MAIN
      OUTCOME MEASURE: Day 15 PB-MRD and bone marrow MRD (BM-MRD) analyzed by six color
      flow cytometry. RESULTS: The sensitivity of day 15 PB-MRD to identify concurrent
      day 15 BM-MRD positivity was 64%, with 100% specificity. The positive and
      negative predictive values were 100% and 62.5%, respectively. PB-MRD was positive
      in 67% of relapsed patients. CONCLUSION: BM-MRD is a well-established prognostic
      factor in B-ALL. We suggest, day 15 PB-MRD could be considered as an early,
      minimally invasive and easily accessible MRD screening option.

PMID- 27889708
TI  - miR-34a is a common link in both HIV- and antiretroviral therapy-induced vascular
      aging.
AB  - Both HIV and antiretroviral therapy could induce vascular aging with unclear
      mechanisms. In this study, via microarray analysis, we identified, for the first
      time, that miR-34a expression was significantly increased in both HIV-infected,
      and antiretroviral agents-treated vessels and vascular endothelial cells (ECs)
      from these vessels. In cultured ECs, miR-34a expression was significantly
      increased by HIV-Tat protein and by the antiretroviral agents,
      lopinavir/ritonavir. Both HIV-Tat protein and antiretroviral agents could induce
      EC senescence, which was inhibited by miR-34a inhibition. In contrast, EC
      senescence was exacerbated by miR-34a overexpression. In addition, the vascular
      ECs isolated from miR-34a knockout mice were resistant to HIV and antiretroviral
      agents-mediated senescence. In vivo, miR-34a expression in mouse vascular walls
      and their ECs was increased by antiretroviral therapy and by HIV-1 Tat transgenic
      approach. miR-34a inhibition could effectively inhibit both HIV-Tat protein and
      antiretroviral therapy-induced vascular aging in mice. The increased miR-34a was
      induced via p53, whereas Sirt1 was a downstream target gene of miR-34a in both
      HIV-Tat protein and antiretroviral agents-treated ECs and vessels. The study has
      demonstrated that miR-34a is a common link in both HIV and antiretroviral therapy
      mediated vascular aging.

PMID- 27889710
TI  - Effect of Withholding Phenobarbitone Maintenance in Neonatal Seizures: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To compare the effect of withholding maintenance phenobarbitone on
      breakthrough seizures. DESIGN: A double blind randomized controlled trial.
      SETTING: Level II neonatal intensive care unit (NICU) of a teaching hospital in
      Northern India. PARTICIPANTS: 152 term and near term neonates (34 weeks of
      gestation age) with admission weight >=2 kg with clinically apparent seizures who
      received intravenous (IV) loading dose of 20 mg/kg of phenobarbitone.
      INTERVENTIONS: After 12 hours of seizure free period of the initial loading dose
      of phenobarbitone, one group received IV maintenance therapy and other 'no
      maintenance' (saline as placebo). MAIN OUTCOME MEASURE: Breakthrough seizures
      from randomization till discharge. RESULTS: Baseline variables were comparable in
      the two groups. Breakthrough seizures occurred in 30 (40%) subjects in placebo
      group and 24 (31.2%) in phenobarbitone group with RR (95% CI) of 1.28 (0.83-1.97)
      (P=0.19). Seizure recurrence, re-hospitali-sation, mortality and abnormal
      neurological assessment until 3 months were comparable in the two groups
      (P>0.05). Babies in either group with breakthrough seizures were more likely to
      be neurologically abnormal at 1 month than babies who did not have breakthrough
      seizures, but this difference decreased by 3 months. CONCLUSION: In term and near
      term neonates, those who respond to loading dose of phenobarbitone after a single
      seizure episode, withholding of phenobarbitone maintenance may not significantly
      increase the risk of breakthrough seizures.

PMID- 27889711
TI  - Immunogenicity and Safety of a Liquid Hexavalent Vaccine in Indian Infants.
AB  - OBJECTIVE: To evaluate the immunogenicity and safety of a fully liquid,
      hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus
      hepatitis B-Haemophilus influenzae type b (DTaP-IPV- HB-PRP~T) vaccine in Indian
      infants. DESIGN: Phase III, single-arm study. SETTING: Two tertiary care
      hospitals. PARTICIPANTS: 177 healthy, 6-week-old infants. INTERVENTION: All
      participants received hepatitis B vaccine and Oral polio vaccine (OPV) at birth
      and DTaP-IPV-HB-PRP~T at 6, 10, 14 weeks of age. MAIN OUTCOME MEASURES: Serum was
      analyzed for immune responses to all antigens 1 month post- 3rd dose; safety was
      assessed for 30 minutes post-vaccination, and for 7 days (solicited reactions)
      and 30 days (unsolicited events). RESULTS: Seroprotection rates were 100% for
      anti-HB (>10 mIU/mL), anti-PRP (>0.15 ug/mL), anti-T (>0.01 IU/mL), anti-polio 1,
      2, and 3 (>8 [1/dil]), and 99.3% for diphtheria (>0.01 IU/mL). For the pertussis
      antigens, vaccine response rate was 93.8% for anti-PT and 99.3% for anti-FHA.
      37.9% and 54.6% of participants experienced at least one solicited injection site
      and systemic reaction, respectively, and 20.3% of participants experienced at
      least one unsolicited event (none of which was related to the vaccination). Four
      serious adverse events (including one death) were reported, but none was related
      to the vaccination. CONCLUSION: The fully liquid DTaP-IPV-HB-PRP~T vaccine is
      highly immunogenic in infants in India when administered in a 6, 10, 14 week
      schedule along with HB and OPV administered at birth, and was well tolerated.

PMID- 27889712
TI  - Serum Procalcitonin for Predicting Significant Infections and Mortality in
      Pediatric Oncology.
AB  - OBJECTIVE: To evaluate the role of serum procalcitonin (PCT) level at admission
      in predicting significant infections and deaths among children on chemotherapy
      presenting with fever. METHODS: Children with clinically significant (CSI) and
      microbiologically documented (MDI) infections were identified using standard
      definitions. Association of PCT with CSI, MDI and mortality was analyzed.
      RESULTS: We evaluated 821 febrile episodes in 316 children. CSI, MDI and deaths
      were seen in 40.9%, 20.1% and 2.9%, respectively. PCT levels ranged from 0.05
      560ng/mL. Median PCT was higher in episodes with CSI (0.80 vs. 0.28) and MDI
      (0.71 vs. 0.34) (P<0.001). PCT >=0.7ng/mL optimally predicted CSI (AUC-0.740) and
      MDI (AUC-0.636). Relative risk of mortality for PCT >=5ng/mL was 7.1. PCT
      >=0.7ng/mL had poor sensitivity (45-55%) but good specificity and NPV (70-90%).
      PCT was elevated in nearly half of documented viral and fungal infections.
      CONCLUSION: PCT predicts significant infections and mortality in pediatric
      oncology but it has poor sensitivity to guide clinical decisions.

PMID- 27889713
TI  - Prognostic Value of Resistive Index in Neonates with Hypoxic Ischemic
      Encephalopathy.
AB  - OBJECTIVE: To evaluate the role of Resistive index measured by cranial doppler
      ultrasonography in predicting the risk of death/ abnormal neurodevelopmental
      outcomes in term neonates with hypoxic ischemic encephalopathy. METHODS: We
      enrolled 50 term asphyxiated neonates with hypoxic ischemic encephalopathy and
      measured resistive index within 72 hours from the anterior cerebral artery.
      Participants underwent tone and developmental assessment at 6-12 months. RESULTS:
      Among the 50 neonates, 25 (50%) had abnormal resistive index (<0.56 or >0.80).
      Presence of abnormal resistive index increased the risk of death/ abnormal
      neurological outcomes at 6-12 months [RR (95% CI): 7.5 (2.0,8.6), P<0.01].
      CONCLUSION: An abnormal resistive index is associated with death/
      neurodevelopmental impairment in neonatal hypoxic ischemic encephalopathy.

PMID- 27889714
TI  - Neonatal Diabetes: A Case Series.
AB  - BACKGROUND: Neonatal diabetes mellitusis a rare disorder with an incidence of 1
      in 2,60,000 live births. METHODS: Retrospective analysis of clinical and genetic
      profile of children admitted with neonatal diabetes mellitus in a tertiary-care
      hospital in Chennai, India over 11 years. RESULTS: Ten children were diagnosed
      with neonatal diabetes of whom 9 had permanent neonatal diabetes mellitus. The
      age range at onset was from 3 days- 5 months. Of the 9 children, KCNJ11 gene
      mutation was positive in one, and ABCC 8 and INS gene mutation in two children
      each. Children with KCNJ11 and ABCC 8 gene mutations were switched over to oral
      sulfonyl urea therapy. CONCLUSION: Few genotypes causing NDM can be managed
      effectively with oral sulfonyl ureas.

PMID- 27889715
TI  - Bedside Infant Manikins for Teaching Newborn Examination to Medical
      Undergraduates.
AB  - OBJECTIVE: To study whether using infant manikins during clinical posting could
      help in teaching newborn examination to undergraduate medical students. METHODS:
      111 final MBBS students were taught newborn examination either by the new method
      which included practice on infant manikins at the bedside before examining babies
      (Group 1) or by the traditional method which involved directly examining babies
      (Group 2). They were tested the next day by validated OSCE stations on important
      aspects of the newborn examination. Marking was done as 0 (completely incorrect),
      1 (partially correct) or 2 (completely correct). Student feedback was also taken.
      RESULTS: Scores were higher, with lesser variance, in Group 1. Student feedback
      was positive, favoring the new method. CONCLUSION: Use of infant manikins at the
      bedside during clinical posting improves the performance of undergraduate
      students in newborn examination.

PMID- 27889716
TI  - Association of Allergic Rhinitis and Sinusitis with Childhood Asthma.
AB  - OBJECTIVE: To study the point prevalence of allergic rhinitis and sinusitis in
      childhood asthma and to examine the relationship among them. METHODS: In 250
      children (age <13 y) with mild-to-moderte asthma, allergic rhinitis was diagnosed
      by clinical plus nasal eosinophilia criteria, and sinusitis was diagnosed
      clinically plus confirmation by computerized tomography scan. RESULTS: The point
      prevalence of allergic rhinitis was 13.6%, and of sinusitis was 2%. On
      multivariate analysis, allergic rhinitis, sinusitis, and family history were
      significantly associated with asthma severity. CONCLUSION: Allergic rhinitis is
      common in childhood asthama, but sinusitis is rare.

PMID- 27889717
TI  - Profile of Neonatal Sepsis due to Burkholderia capacia Complex.
AB  - We report the result of retrospective record review of the clinical profile of 59
      neonates who presented to a tertiary-care extramural neonatal unit with
      Burkholderia cepacia complex infection. Among the 3265 admissions over 45 months,
      incidence of Burkholderia sepsis was 18 per 1000 admissions. Case fatality rate
      was 17%. Most (95%) isolates were sensitive to cotrimoxazole.

PMID- 27889718
TI  - Parents' Evaluation of Developmental Status (PEDS) in Screening for Developmental
      Delay in Thai Children Aged 18-30 Months.
AB  - The PEDS-Thai is a developmental screening tool. We studied its diagnostic
      performance among 137 Thai children (48.9%) aged 18-30 month. It had a
      sensitivity of 92.8% and a specificity of 49.2%. The positive and negative
      likelihood ratios were 1.82 and 0.14 when compared with clinical diagnosis and
      diagnostic tool, the Mullen Scales of Early Learning.

PMID- 27889719
TI  - Causes of Death among Children Aged >5 Years in a Public Hospital in New Delhi.
AB  - Retrospective analysis was done for 3817 children aged 5-12 years admitted in a
      tertiary-care, public hospital in New Delhi between January to December, 2015.
      Mortality rate was 5.8%. About 47.1% deaths were due to central nervous system
      involvement; viral meningoencephalitis being the predominant cause. Overall,
      infectious diseases caused >80% of deaths. Public health interventions to reduce
      child mortality need to review such data for effective measures.

PMID- 27889720
TI  - Clearing Pediatric Airways.

PMID- 27889721
TI  - Concept of Health Care Counseling for Pediatricians.
AB  - Health care counseling (HCC) is a relatively new concept that amalgamates human
      biology, human psychology and medical sociology principles, and applies the same
      in real-time clinical situations. In India, there is a real paucity of trained
      mental health personnel, and hence counseling services are restricted to few
      departments. HCC is especially important for the child population, as the
      pediatricians need to partner the parenting responsibilities in different illness
      care settings covering the period from newborn to adolescence. This paper
      proposes steps for further development of the concept, expertise and systematic
      training program for health personnel, as an activity of Centre for Health Care
      Counseling Studies under Kerala University of Health Sciences. Once the process
      is documented, we hope that the same would be made available to other states in
      India.

PMID- 27889722
TI  - Vitamin D and its Role in the Management and Prevention of Lower Respiratory
      Tract Infections in Infants and Young Children.

PMID- 27889723
TI  - Vitamin D Supplementation for Treatment and Prevention of Pneumonia in Under-five
      Children: A Randomized Double-blind Placebo Controlled Trial.
AB  - OBJECTIVE: To evaluate the efficacy of single oral mega-dose of Vitamin D3 for
      treatment and prevention of pneumonia in under-five children. DESIGN: Randomized,
      double blind, placebo-controlled trial. SETTING: Tertiary-care hospital.
      PARTICIPANTS: 324 children (of 980 assessed) between 6 mo-5 y age (median (IQR):
      12 (7,19.8) mo) with WHO-defined severe pneumonia. Of these, 126 (39%) were
      vitamin D deficient (serum 25(OH)D <12 ng/mL). INTERVENTION: 100,000 IU of oral
      cholecalciferol (n= 162) or placebo (n= 162) in single dose, administered at
      enrolment. Outcome variables: Primary: Time to resolution of severe pneumonia and
      proportion of children having recurrence of pneumonia in next 6 months;
      Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG, IgM, and
      cathelicidin 2 weeks following supplementation; and time taken for overall
      resolution of illness. OUTCOME VARIABLES: Primary: Time to resolution of severe
      pneumonia and proportion of children having recurrence of pneumonia in next 6
      months; Secondary: Change in serum levels of 25(OH)D; immunoglobulins IgA, IgG,
      IgM, and cathelicidin 2 weeks following supplementation; and time taken for
      overall resolution of illness. RESULTS: Median (95% CI) time for resolution of
      severe pneumonia was 30 (29, 31) h in the vitamin D group as compared to 31
      (29,33) h in the placebo group [adjusted hazard ratio (95% CI): 1.39 (1.11,
      1.76); P = 0.005]. The risk of recurrence of pneumonia in next 6 months was
      comparable in the two groups [placebo: 36/158 (22.8%); vitamin D: 39/156 (25%);
      RR (95% CI): 1.13 (0.67,1.90); P 0.69]. Proportion of vitamin D deficient
      children declined from 38% to 4% in the supplementation group, and from 41% to
      33% in the placebo group, two weeks after supplementation. There was no
      significant effect of vitamin D supplementation on serum levels of cathelicidin,
      IgA and IgG. The time taken for complete recovery from pneumonia, duration of
      hospitalization, and fever clearance time were comparable for the two groups. No
      adverse event was noted related to the intervention. CONCLUSION: There is no
      robust evidence of a definite biological benefit, either for therapy or
      prevention, to suggest a routine megadose supplement of vitamin D3 for under-five
      children with severe pneumonia.

PMID- 27889724
TI  - Phenotype of Dent Disease in a Cohort of Indian Children.
AB  - OBJECTIVE: To describe the clinical and genotypic features of Dent disease in
      children diagnosed at our center over a period of 10 years. DESIGN: Case series.
      SETTING: Pediatric Nephrology Clinic at a referral center in Northern India.
      METHODS: The medical records of patients with Dent disease diagnosed and followed
      up at this hospital from June 2005 to April 2015 were reviewed. The diagnosis of
      Dent disease was based on presence of all three of the following: (i) low
      molecular weight proteinuria, (ii) hypercalciuria and (iii) one of the following:
      nephrolithiasis, hematuria, hypophosphatemia or renal insufficiency, with or
      without mutation in CLCN5 or OCRL1 genes. RESULTS: The phenotype in 18 patients
      diagnosed with Dent disease during this period was characterized by early age at
      onset (median 1.8 y), and polyuria, polydipsia, salt craving, hypophosphatemic
      rickets and night blindness. Rickets was associated with severe deformities,
      fractures or loss of ambulation in six patients. Nephrocalcinosis was present in
      three patients, while none had nephrolithiasis. Generalized aminoaciduria was
      seen in 13 patients, two had glucosuria alone, and one had features of Fanconi
      syndrome. Over a median follow up of 2.7 years, one patient developed renal
      failure. Genetic testing (n=15) revealed 5 missense mutations and 3 nonsense
      mutations in CLCN5 in 13 patients. Five of these variations (p.Met504Lys,
      p.Trp58Cys, p.Leu729X, p.Glu527Gln and p.Gly57Arg) have not been reported outside
      the Indian subcontinent. CONCLUSION: Our findings suggest a severe phenotype in a
      cohort of Indian patients with Dent disease.

PMID- 27889725
TI  - Fluid Supplementation versus No Fluid Supplementation in Late Preterm and Term
      Neonates with Asymptomatic Polycythemia: A Randomized Controlled Trial.
AB  - OBJECTIVE: To compare supplemental intravenous fluids with no supplementation in
      asymptomatic polycythemic late preterm and term neonates. METHODS: 55 infants
      with venous haematocrit of 65-75 were randomly allocated to receive either 25
      mL/kg IV normal saline over 6-8 hours or routine fluids. They were followed up
      for 48 hours. RESULTS: There was no significant difference between fluid
      supplementation and control groups regarding need for partial exchange
      transfusion [6/27 (22.2%) vs 8/28 (28.6%); P=0.59]. CONCLUSION: We did not find
      any evidence of clinical benefit with IV fluid supplementation in late preterm
      and term neonates with asymptomatic polycythemia (PCV 65-75).

PMID- 27889726
TI  - Prolonged Infusion of Dexmedetomidine in Critically-ill Children.
AB  - OBJECTIVE: To describe main indications, doses, length of infusion and side
      effects related to dexmedetomidine infusion. METHODS: Observational and
      retrospective study evaluating dexmedetomidine use in pediatric intensive care
      unit. RESULTS: 77 children received dexmedetomidine infusion longer than 6 hours
      for mechanical ventilation weaning (32.5%), post- neurosurgery and post-upper
      airway surgery (24.7%), non-invasive ventilation (13%), refractory tachycardia
      (6.5%) and other causes (23.3%). After 6 hours of infusion, significant decrease
      in mean arterial pressure and heart rate was observed in all groups. Six children
      (8%) required withdrawal of drug because of possible side effects: hypotension,
      bradycardia and somnolence. CONCLUSION: Dexmedetomidine may be used as sedative
      in critically ill children without much side effects.

PMID- 27889727
TI  - Longitudinal Growth in Children and Adolescents with Type 1 Diabetes.
AB  - OBJECTIVE: To study longitudinal growth in children with type 1 diabetes
      mellitus. METHODS: Anthropometry, disease duration, insulin regimens and HbA1C
      recorded from patients with diabetes enrolled in a specialty clinic. RESULTS: 160
      children (75 boys; mean (SD) age 9.4 (3.3) y) were enrolled. 35% children had low
      (<25th centile) height velocity. Disease duration and HbA1C affected height
      velocity (adjusted for puberty). Children on basal-bolus had higher height
      velocity Z scores than those on a split mix regimen [(0.5(1.6) vs. -0.3(1.4),
      P<0.05)]. Children diagnosed before 5 years of age had lowest height velocity. Of
      the children who reached final height, 53% remained below target height.
      CONCLUSION: Children with type 1 diabetes mellitus have lower height velocity
      compared to healthy children; those diagnosed at younger age were at higher risk
      for growth failure.

PMID- 27889728
TI  - Pediatric Inflammatory Bowel Disease.
AB  - Background: The incidence of inflammatory bowel disease is increasing in the
      pediatric population worldwide. NEED AND PURPOSE OF REVIEW: There is paucity of
      high quality scientific data regarding pediatric inflammatory bowel disease. Most
      of the guidelines are offshoots of work done in adults, which have been adapted
      over time to diagnose and treat pediatric patients. This is in part related to
      the small numbers in pediatric inflammatory bowel disease and less extensive
      collaboration for multicentric trials both nationally and internationally.
      METHODS: A literature search was performed using electronic databases i.e. Pubmed
      and OVID, using keywords: pediatric, inflammatory bowel disease, Crohns disease,
      Ulcerative colitis, epidemiology and guidelines. This article amalgamates the
      broad principles of diagnosing and managing a child with suspected inflammatory
      bowel disease. MAIN CONCLUSIONS: 25% of the patients with inflammatory bowel
      disease are children and and young adolescents. The primary concern is its impact
      on growth velocity, puberty and quality of life, including psychosocial issues.
      Treatment guidelines are being re-defined as the drug armamentarium is
      increasing. The emphasis will be to achieve mucosal healing and normal growth
      velocity with minimal drug toxicity.

PMID- 27889729
TI  - Accurate References Add to the Credibility.

PMID- 27889730
TI  - Comparison of Lung Ultrasonography and Chest Radiography for Diagnosis of
      Childhood Pneumonia: Evidence based Medicine Viewpoint.

PMID- 27889731
TI  - Comparison of Lung Ultrasonography and Chest Radiography for Diagnosis of
      Childhood Pneumonia: Pediatric Emergency Medicine Physicians Viewpoint.

PMID- 27889732
TI  - Distal Renal Tubular Acidosis Associated with Celiac Disease and Thyroiditis.
AB  - BACKGROUND: Association of distal renal tubular acidosis (RTA) with autoimmune
      diseases is extremely rare in children. CASE CHARACTERISTICS: 12-year-old girl
      with distal RTA. Despite resolution of acidosis on bicarbonate, she continued to
      have poor growth and delayed puberty. Investigations revealed autoimmune
      thyroiditis and celiac disease. OUTCOME: Levothyroxine and gluten-free diet were
      initiated. Child gained height and weight and had onset of puberty after gluten
      withdrawal. MESSAGE: Distal RTA in children may rarely be of autoimmune etiology.

PMID- 27889733
TI  - Steroid Pulse Therapy for Kawasaki Disease Complicated with Myocarditis.
AB  - BACKGROUND: The clinical management of intravenous immunoglobulin-resistant
      Kawasaki disease shock syndrome (KDSS) is obscure. CASE CHARACTERISTICS: Three
      children presented with intravenous immunoglobulin-resistant KDSS complicated
      with myocarditis. OUTCOME: All cases were successfully managed with steroid pulse
      therapy. MESSAGE: Steroid pulse therapy is effective in immunoglobulin-resistant
      KDSS.

PMID- 27889734
TI  - Retained Capsule Endoscope.
AB  - BACKGROUND: Capsule endoscopy was invented to visualize the entire small
      intestine in a non- invasive manner in adults. CASE CHARACTERISTICS: 1 y, 9 mo
      old boy presented with generalized edema for last 3 months. His routine
      investigations, including the upper gastrointestinal endoscopy, colonoscopy, and
      contrast enhanced computed tomography scan (CECT) were normal. In view of
      clinical suspicion of protein losing enteropathy, we planned capsule endoscopy.
      OBSERVATION: The capsule was not passed even after 3 weeks. Laparoscopy revealed
      impacted capsule in a dilated intestinal loop proximal to an ileal stricuture.
      MESSAGE: Capsule endoscopy should be used judiciously in children.

PMID- 27889735
TI  - A Novel Protein C Mutation Causing Neonatal Purpura Fulminans.
AB  - BACKGROUND: Neonatal purpura fulminans due to congenital protein C deficiency is
      a rare disorder. CASE CHARACTERISTICS: A four-day-old neonate presented with
      multiple necrotic skin lesions with abnormal coagulation profile. INTERVENTION
      AND OUTCOME: Skin lesions responded to repeated plasma transfusions but the
      neonate developed bilateral retinal detachment. A novel homozygous PROC gene
      mutation was noted in the neonate. MESSAGE: Molecular diagnosis and prenatal
      counseling in neonatal purpura fulminans are vital considering the poor outcome.

PMID- 27889736
TI  - Vitamin D and Metabolic Bone Parameters in Preterm Neonates.
AB  - We measured serum levels of 25-hydroxy vitamin D (25(OH) D) in 79 preterm
      neonates (?32 wk), and correlated it with serum ionized calcium (Ca++) levels at
      48-72 h and serum phosphorus and alkaline phosphatase levels at 2-3 weeks of age.
      The mean (SD) 25 (OH)D level was 14.8 (7.0) ng/mL. 25(OH)D levels had a weak
      positive correlation with Ca++ (r=0.299) and phosphorus (r=0.186), and a negative
      correlation with alkaline phosphatase (r=-0.523).

PMID- 27889737
TI  - Immune Thrombocytopenic Purpura in Children of Eastern Henan Province, China.
AB  - In this retrospective cohort study conducted in 63 children with idiopathic
      thrombocytopenic purpura (ITP) in China; petechiae, bruises and bleeding were the
      major presentations. Most cases required therapy with one/more treatment options.

PMID- 27889738
TI  - Hackers Spy Scientists.

PMID- 27889739
TI  - Concomitant Infections Should not Deter Clinicians from Diagnosing Kawasaki
      Disease.

PMID- 27889740
TI  - Pediatric Multiple Sclerosis.

PMID- 27889741
TI  - Faculty Promotion Guidelines, Authorship and Indexing Issues Need More
      Deliberations.

PMID- 27889742
TI  - Faculty Promotion Guidelines: Authorship and Indexing Issues Need More
      Deliberations: Authors Reply.

PMID- 27889743
TI  - The Academy Should take up the Issue of Off label Prescriptions.

PMID- 27889744
TI  - Non availability of Cloxacillin, A Deterrent for Rational Antimicrobial Practice.

PMID- 27889745
TI  - Retinoblastoma Mimicking Orbital Cellulitis.

PMID- 27889746
TI  - Distinct in vitro Complement Activation by Various Intravenous Iron Preparations.
AB  - BACKGROUND: Intravenous (IV) iron preparations are widely used in the treatment
      of anemia in patients undergoing hemodialysis (HD). All IV iron preparations
      carry a risk of causing hypersensitivity reactions. However, the
      pathophysiological mechanism is poorly understood. We hypothesize that a relevant
      number of these reactions are mediated by complement activation, resulting in a
      pseudo-anaphylactic clinical picture known as complement activation-related
      pseudo allergy (CARPA). METHODS: First, the in-vitro complement-activating
      capacity was determined for 5 commonly used IV iron preparations using functional
      complement assays for the 3 pathways. Additionally, the preparations were tested
      in an ex-vivo model using the whole blood of healthy volunteers and HD patients.
      Lastly, in-vivo complement activation was tested for one preparation in HD
      patients. RESULTS: In the in-vitro assays, iron dextran, and ferric
      carboxymaltose caused complement activation, which was only possible under
      alternative pathway conditions. Iron sucrose may interact with complement
      proteins, but did not activate complement in-vitro. In the ex-vivo assay, iron
      dextran significantly induced complement activation in the blood of healthy
      volunteers and HD patients. Furthermore, in the ex-vivo assay, ferric
      carboxymaltose and iron sucrose only caused significant complement activation in
      the blood of HD patients. No in-vitro or ex-vivo complement activation was found
      for ferumoxytol and iron isomaltoside. IV iron therapy with ferric carboxymaltose
      in HD patients did not lead to significant in-vivo complement activation.
      CONCLUSION: This study provides evidence that iron dextran and ferric
      carboxymaltose have complement-activating capacities in-vitro, and
      hypersensitivity reactions to these drugs could be CARPA-mediated.

PMID- 27889748
TI  - MiR-146a Regulates Inflammatory Infiltration by Macrophages in
      Polymyositis/Dermatomyositis by Targeting TRAF6 and Affecting IL-17/ICAM-1
      Pathway.
AB  - BACKGROUND/AIMS: The primary objective of this study was to investigate the role
      of miR-146a in inducing the inflammatory infiltration of macrophages in
      polymyositis/dermatomyositis (PM/DM) through targeting TNF receptor associated
      factor 6 (TRAF6), which may further down-regulate the Interleukin-17 (IL
      17)/Intercellular Adhesion Molecule 1 (ICAM-1) pathway. METHODS: Biopsies were
      collected from PM/DM patients and healthy volunteers. PM/DM model establishment
      and macrophage isolation were performed on Sprague Dawley (SD) rats. Model rats
      and macrophages were treated with anti-IL-17, anti-ICAM-1, miR-146a mimics, miR
      146a inhibitors, and TRAF6 siRNAs. Serum creatine phosphokinase (S-CK) expression
      was assessed using double antibody sandwich enzyme-linked immunosorbent assay
      (ELISA) assay, and immunohistochemistry assay was performed to analyze CD163
      expression in muscle samples. Furthermore, we used transwell assay to test cell
      migration; RT-PCR and western blot were carried out to determine the expression
      of miR-146a, TRAF6, IL-17, and ICAM-1. RESULTS: The S-CK, TRAF6, IL-17 and ICAM-1
      levels were higher in PM/DM patients compared with healthy controls and were down
      regulated after the conventional treatment. Treatment with miR-146a mimics, anti
      IL-17 and anti-ICAM-1 decreased the expression of IL-17 and ICAM-1, whereas miR
      146a inhibitors exerted the opposite effects. The effects of miR-146a inhibitors
      were suppressed by treatment with TRAF6 siRNA. In addition, the luciferase
      reporter assay validated the targeting relationship between miR-146a and TRAF6.
      CONCLUSIONS: MiR-146a regulates inflammatory macrophage infiltration in PM/DM by
      targeting TRAF6 and affecting the IL-17/ICAM-1 pathway.

PMID- 27889747
TI  - Alisol A 24-Acetate Prevents Hepatic Steatosis and Metabolic Disorders in HepG2
      Cells.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely associated with
      metabolic disorders including hepatic lipid accumulation and inflammation. Alisol
      A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic
      activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we
      hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present
      study was conducted to investigate the therapeutic effects and potential
      mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids
      (FFAs) induced NAFLD cell model. METHODS: This study was divided into four groups
      including Control group, Model group (FFA group), Alisol A 24-acetate (FFA+A)
      group, Fenofibrate (FFA+F) group. Preventive role of Alisol A 24-acetate was
      evaluated using 10uM Alisol A 24-acetate plus 1 mM FFA (oleate:palmitate=2:1)
      incubated with HepG2 cells for 24 h, which was determined by Oil Red O Staining,
      Oil Red O based colorimetric assay and intracellular triglyceride (TG) content.
      Besides, the inflammatory cytokines tumor necrosis factor (TNF)- alpha,
      interleukin (IL)-6 levels as well as the protein and mRNA expressions that were
      involved in fatty acid synthesis and oxidation including Adiponectin, AMP
      activated protein kinase (AMPK) alpha, peroxisome proliferator-activated receptor
      (PPAR) alpha, sterol regulatory element binding protein 1c (SREBP-1c), acetyl-CoA
      carboxylase (ACC), fatty acid synthase (FAS), carnitine palmitoyltransferase 1
      (CPT1) and acyl coenzyme A oxidase 1 (ACOX1) were detected. RESULTS: Alisol A 24
      acetate significantly decreased the numbers of lipid droplets, Oil Red O lipid
      content, and intracellular TG content. Besides, inflammatory cytokines TNF-alpha,
      IL-6 levels were markedly inhibited by Alisol A 24-acetate. Furthermore, Alisol A
      24-acetate effectively increased the protein and mRNA expressions of Adiponectin,
      the phosphorylation of AMPKalpha, CPT1 and ACOX1, whereas decreased SREBP-1c, the
      phosphorylation of ACC and FAS at both protein and mRNA levels. However, there
      was no significant effect on the protein and mRNA expressions of PPARalpha by
      Alisol A 24-acetate. CONCLUSIONS: These results demonstrated that Alisol A 24
      acetate effectively ameliorated hepatic steatosis likely through Adiponectin,
      which activated AMPKalpha signaling pathways via down-regulating SREBP-1c, ACC,
      FAS and up-regulating CPT1 and ACOX1, and inhibited inflammation. Thereby, Alisol
      A 24-acetate could be a promising candidate for the treatment of NAFLD.

PMID- 27889749
TI  - Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on
      the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion.
AB  - BACKGROUND/AIMS: An enriched environment (EE) ameliorates learning and memory
      impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen
      activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and
      deleterious effects on the nervous system during the progression of ischemia.
      METHODS: The present study investigated whether p38 MAPK participates in the
      process by which EE exposure ameliorates the cognitive deficits induced by
      chronic cerebral hypoperfusion. RESULTS: EE exposure significantly enhanced the
      cognitive performance of vascular dementia (VD) model rats, and p38 MAPK protein
      decreased in parallel with cognitive improvements. Inhibition of p38 MAPK
      function by its selective inhibitor SB203580 improved the cognition index of VD
      rats and upregulated p38 MAPK expression with p38 MAPK antisense
      oligodeoxynucleotides. This impaired cognition in VD rats could not be rescued by
      EE exposure. CONCLUSION: p38 MAPK participates in the process by which EE
      exposure ameliorates cognitive deficits induced by chronic cerebral
      hypoperfusion.

PMID- 27889751
TI  - Targeted Therapy of Head and Neck Cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) is one of the most common solid
      cancers worldwide. It is mainly caused by exposure to tobacco smoke and alcohol
      as well as infection with the human papilloma virus (HPV). The prognosis is poor,
      especially once it recurs or metastasizes. Current therapeutic options include
      surgery, radio- and chemotherapy. Epidermal growth factor receptor (EGFR)
      inhibitors are so far the only targeted agents that have been approved in head
      and neck cancer. Primary or secondary resistance is frequent or will eventually
      develop. Several driver mutations and other genomic aberrations have been
      described in HNSCC including EGFR overexpression and amplification. Yet, no
      predictive biomarkers for the application of EGFR inhibitors have been
      identified. Further targeted agents are in development for HNSCC, of which
      inhibitors of the PI3K pathway are the closest to clinical application. In recent
      years, the incidence of HPV-driven HNSCC has risen in Western countries. HPV
      positive and -negative HNSCC are distinct molecular tumor entities, and
      consequences for targeted therapies have been discussed. This review looks at
      approved and investigational targeted treatment strategies as well as potential
      predictive biomarkers such as the HPV status to guide treatment.

PMID- 27889750
TI  - Metformin Protects Neurons against Oxygen-Glucose Deprivation/Reoxygenation 
      Induced Injury by Down-Regulating MAD2B.
AB  - BACKGROUND/AIMS: Metformin, the common medication for type II diabetes, has
      protective effects on cerebral ischemia. However, the molecular mechanisms are
      far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor
      of the anaphase-promoting complex (APC), is widely expressed in hippocampal and
      cortical neurons and plays an important role in mediating high glucose-induced
      neurotoxicity. The present study investigated whether metformin modifies the
      expression of MAD2B and to exert its neuroprotective effects in primary cultured
      cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a
      widely used in vitro model of ischemia/reperfusion. METHODS: Primary cortical
      neurons were cultured, deprived of oxygen-glucose for 1 h, and then recovered
      with oxygen-glucose for 12 h and 24 h. Cell viability was measured by detecting
      the levels of lactate dehydrogenase (LDH) in culture medium. The levels of MAD2B,
      cyclin B and p-histone 3 were measured by Western blot. RESULTS: Cell viability
      of neurons was reduced under oxygen-glucose deprivation/reoxygenation (OGD/R).
      The expression of MAD2B was increased under OGD/R. The levels of cyclin B1, which
      is a substrate of APC, were also increased. Moreover, OGD/R up-regulated the
      phosphorylation levels of histone 3, which is the induction of aberrant re-entry
      of post-mitotic neurons. However, pretreatment of neurons with metformin
      alleviated OGD/R-induced injury. Metformin further decreased the expression of
      MAD2B, cyclin B1 and phosphorylation levels of histone 3. CONCLUSION: Metformin
      exerts its neuroprotective effect through regulating the expression of MAD2B in
      neurons under OGD/R.

PMID- 27889752
TI  - Dietary and Alcohol Intake and Central Nervous System Tumors in Adults: Results
      of the CERENAT Multicenter Case-Control Study.
AB  - BACKGROUND: Little is known about the relationship between diet and central
      nervous system (CNS) tumors, especially in terms of their histological subtypes.
      This study investigated the overall associations between food groups, alcohol
      intake and CNS tumors, and in particular about the associations between
      neuroepithelial tumors and meningiomas. METHODS: Data were collected through the
      CERENAT (CEREbral tumors: a NATional study) case-control study conducted in
      France during the period 2004-2010. Data were available for 1,479 subjects (494
      cases, including 201 neuroepithelial tumors, 193 meningiomas, 100 other CNS
      tumors, and their 985 matched controls). Conditional logistic regressions for
      matched sets were adjusted based on the participants' educational level,
      occupation, smoking status and frequency of food group consumption. RESULTS: A
      heavy consumption of grilled meat and poultry was associated with neuroepithelial
      tumors in a dose-related relationship (ORQ4vsQ1 = 3.72, 95% CI 1.62-8.52, p =
      0.005). Higher fruit and vegetable intake was inversely associated with
      meningiomas (for fruits: ORQ4vsQ1 = 0.38, 95% CI 0.17-0.87, p = 0.06, for
      vegetables ORQ4vsQ1 = 0.26, 95% CI 0.11-0.62, p = 0.007). Consumption of alcohol
      on a daily basis was inversely associated with CNS tumors especially for
      meningiomas (ORQ4vsQ1 = 0.33, 95% CI 0.18-0.61, p = 0.001). CONCLUSIONS: Results
      obtained in terms of grilled meat, fruits and vegetables consumption were in line
      with those published in epidemiological literature. Contradictions in results
      between neuroepithelial tumors and meningiomas confirmed the need to analyze the
      effects of dietary factors on the basis of the histological subtypes of CNS
      tumors.

PMID- 27889753
TI  - Renal Denervation Attenuates Multi-Organ Fibrosis and Improves Vascular
      Remodeling in Rats with Transverse Aortic Constriction Induced Cardiomyopathy.
AB  - BACKGROUND/AIMS: To investigate the effects of renal denervation (RDN) on multi
      organ fibrosis and vascular remodeling in cardiomyopathy. METHODS: Thirty-six
      male Sprague-Dawley rats underwent transverse aortic constriction (TAC). Five
      weeks later, 28 surviving TAC rats were randomly assigned to three groups: (1)
      RDN, (2) Sham, (3) Carvedilol. Six male Sham TAC rats served as the Control. Ten
      weeks after TAC, samples were collected. RESULTS: TAC rats showed an increased
      diastolic interventricular septal thickness at week 5. At 10 weeks, Masson
      staining showed that left ventricular and renal glomerular fibrosis were
      significantly reduced in RDN compared with Sham group. In comparison to Sham
      group, hepatic perivascular fibrosis was attenuated in both RDN and Carvedilol
      group, so were the media thickness and the media/lumen of aorta. The plasma
      levels of B-type natriuretic peptide (BNP), Cystatin C (Cys-C), Alanine
      Transaminase, angiotensin II (Ang II), transforming growth factor beta 1 (TGF
      beta1), and malondialdehyde increased, and total superoxide dismutase (T-SOD)
      decreased in Sham but not in RDN group, compared with Control group. Both RDN and
      Carvedilol reduced the Cys-C and TGF-beta1 levels, and restored T-SOD
      concentration, compared with Sham group. While only RDN lowered the plasma levels
      of BNP and Ang II. No significant effects of RDN on blood pressure (BP) and heart
      rate (HR) were oberved. CONCLUSIONS: RDN can attenuate multi-organ fibrosis and
      improve vascular remodeling independent of BP and HR change in TAC-induced
      cardiomyopathy. These effects of RDN may be associated with the direct inhibition
      of renin-angiotensin-aldosterone system and oxidative stress.

PMID- 27889755
TI  - Prevalence of the Janus Kinase 2 V617F Mutation in Patients with End-Stage Renal
      Disease.

PMID- 27889754
TI  - Serous Cystadenoma of the Pancreas: Potentials and Pitfalls of a Preoperative
      Cytopathologic Diagnosis.
AB  - OBJECTIVES: Pancreatic serous cystadenomas (SCAs) are benign tumors.
      Technological advances in imaging have led to increased recognition of
      asymptomatic pancreatic cysts, consequently increasing the demand for
      cytomorphologic evaluations of cyst fluid. STUDY DESIGN: A retrospective search
      through the pathology archives over an 11-year period was performed to identify
      SCAs from pancreatectomy specimens with a presurgical pancreatic EUS-guided fine
      needle aspiration (FNA). RESULTS: Fifty-one FNAs were identified. The average
      patient age was 59.9 years and 34 (67%) were female. Thirty-five (69%) of the
      SCAs were located in the body or tail of the pancreas. SCAs ranged in size from
      1.3 to 8.0 cm (mean 4.9). On imaging, features suggestive of SCA were seen in 7
      (14%) cases. The cytologic diagnoses were as follows: SCA in 5 (10%) cases,
      suspicious for mucin-producing neoplastic cyst in 4 (8%), pseudocyst in 4 (8%),
      and benign ductal and/or acinar epithelium, not otherwise specified in 24 (47%).
      Additionally, 14 (27%) cases were deemed nondiagnostic. CONCLUSIONS: A
      cytopathologic diagnosis of SCA on FNA is extremely difficult. The salient
      cytomorphologic features for identifying SCAs included scant cellularity, a
      mostly clear background, absence of extracellular mucin, hemosiderin-laden
      macrophages, and loose fragments of cuboidal cells with a notable absence of
      necrosis, atypia, and mitoses.

PMID- 27889756
TI  - Liquid Chromatography/Mass Spectrometry Reveals the Effect of Lactobacillus
      Treatment on the Faecal Metabolite Profile of Rats with Chronic Renal Failure.
AB  - BACKGROUND/AIM: Chronic kidney disease is accompanied by changes in the gut
      microbiome and by an increase in the number of gut pathogenic bacteria. The aim
      of this study was to investigate the difference of the faecal metabolic profiles
      in rats with uremia, and to determine whether the altered metabolites in the rats
      with uremia can be restored by Lactobacillus. METHODS: Thirty rats were randomly
      divided into 3 groups: sham, uremia and uremia + probiotic (UP) groups. The rats
      in uremia and UP groups were prepared through surgical renal mass 5/6 ablation.
      The rats in the UP group received Lactobacillus LB (1 ml, 109 CFU/ml) through
      gavage every day for 4 weeks. The rats were fed with a standard diet. Faecal
      samples were analysed through ultra performance liquid chromatography/mass
      spectrometry. Statistical analyses were performed using MetaboAnalyst and MATLAB.
      RESULTS: A total of 99, 324 and 177 significantly different ion peaks were
      selected between sham and uremia groups; sham and UP groups; and uremia and UP
      groups, respectively. In the 3 groups, 35 significantly altered metabolites were
      identified; of the 35 metabolites, 27 initially increased and then decreased; by
      contrast, 8 metabolites initially decreased and then increased. The 35
      metabolites were subjected to pathway analysis in MetaboAnalyst. CONCLUSIONS:
      Faecal metabolites were significantly altered in rats with uremia; these changes
      were partially reversed by Lactobacillus.

PMID- 27889757
TI  - Morphological and Metabolic Alteration of Cerebellum in Patients with Post-Stroke
      Depression.
AB  - BACKGROUND: To study morphological and metabolic changes of cerebellum with
      multimodality magnetic resonance imaging (MRI) and proton magnetic resonance
      spectroscopy (1H-MRS), respective, to explore correlation between cerebellum
      alteration and severity of depression in patients with post-stroke depression.
      METHODS: 60 subjects, including 40 stroke patients and 20 healthy volunteers were
      enrolled. Depression of stroke patients was tested by Self-rating Depression
      Scale (SDS) and Hamilton Depression Scale (HAMD), based on which stroke-patients
      were grouped into post-stroke depression (PSD group) and without post-stroke
      depression (CONT group). RESULTS: Volume of cerebellum decreased in PSD group and
      CONT group compared with healthy volunteer (NORM) group. White matter of
      cerebellum in PSD group and CONT group was disrupted; such disruption was
      significantly in PSD group. In addition, there was correlation between cerebellum
      volume and FA and HDRS scores (P<00.01). The Cho/Cr and Cho/NAA ratios in
      cerebellum contralateral to stroke lesion in PSD were higher than those in NORM
      group (P<0.05). Cho/Cr and Cho/NAA ratios in contralateral cerebellum and ratio
      difference of Cho/Cr in bilateral cerebellum were positively correlated with HAMD
      scales (P<0.05). CONCLUSION: Morphologic and metabolic alterations are evident in
      patients with post-stroke depression, indicating possible involvement of
      cerebellum in post-stroke-depression occurrence.

PMID- 27889758
TI  - Stimulation of Suicidal Erythrocyte Death by Rottlerin.
AB  - BACKGROUND/AIMS: The phytochemical polyphenol rottlerin is a potent activator of
      diverse Ca2+ -sensitive K+ channels. Those channels play a decisive role in the
      execution of eryptosis, the suicidal death of erythrocytes, which is
      characterized by cell shrinkage and cell membrane scrambling with
      phosphatidylserine translocation to the erythrocyte surface. Signaling involved
      in the stimulation of eryptosis includes increase of cytosolic Ca2+ activity
      ([Ca2+]i) and ceramide. The present study explored, whether rottlerin induces
      eryptosis and, if so, to test for the involvement of Ca2+ entry and ceramide.
      METHODS: Flow cytometry was employed to estimate phosphatidylserine exposure at
      the cell surface from annexin-V-binding, cell volume from forward scatter,
      [Ca2+]i from Fluo3-fluorescence, and ceramide abundance utilizing specific
      antibodies. Hemolysis was quantified by determination of haemoglobin
      concentration in the supernatant. RESULTS: A 48 hours exposure of human
      erythrocytes to rottlerin (1 - 5 uM) significantly increased the percentage of
      annexin-V-binding cells, an effect paralleled by significant decrease of forward
      scatter. Up to 5 uM rottlerin failed to significantly increase average Fluo3
      fluorescence. Rottlerin (5 uM) did, however, significantly increase the ceramide
      abundance. Rottlerin (5 uM) further significantly increased hemolysis. The effect
      of rottlerin (5 uM) on annexin-V-binding was virtually abolished by removal of
      extracellular Ca2+. CONCLUSIONS: Rottlerin stimulates eryptosis with erythrocyte
      shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect
      paralleled by and at least in part due to Ca2+ entry and ceramide.

PMID- 27889759
TI  - Cytomorphological Features Useful to Prevent Errors in the Diagnosis of
      Pancreatic Adenocarcinoma by Fine Needle Aspiration Cytology.
AB  - OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration (FNA) is now
      widely used as a primary tool to diagnose pancreatic neoplasms. However, criteria
      that can reduce the risk of overdiagnosing pancreatic adenocarcinoma by FNA have
      not been adequately defined in the literature. This study aims to identify
      characteristic cytomorphological features that are helpful in distinguishing
      pancreatic adenocarcinoma from its mimics. STUDY DESIGN: Five false-positive FNA
      cases (group A) diagnosed as adenocarcinoma (4 cases) and suspicious for
      adenocarcinoma (1 case) by FNA, were identified by searching our laboratory
      information system. Cytomorphological features of group A cases were compared to
      12 true-positive, histologically confirmed FNA cases (group B). RESULTS:
      Subsequent histological follow-ups of 5 misdiagnosed FNA cases showed 2 cases of
      intraductal papillary mucinous neoplasm with focal high-grade dysplasia, 1 case
      attributed to tumor contamination from a gastroesophageal junction
      adenocarcinoma, and 2 cases of pancreatic intraepithelial neoplasia
      (PanIN1/reactive change and PanIN2, respectively). Cytomorphological features
      present in both groups A and B included nuclear enlargement/overlapping, mild to
      moderate anisonucleosis, granular chromatin and prominent nucleoli. However, 1 or
      more of these 4 characteristic morphological features such as 3-dimensional
      cluster with cell disorientation, isolated malignant cells, irregular nuclear
      contour/nuclear grooves/notches (<under>></under>5% atypical cell population),
      and marked nuclear size variation 1:4 or higher was mainly present in
      adenocarcinoma. CONCLUSIONS: A combination of at least 2 of these 4
      characteristic cytomorphological features needs to be present before rendering an
      unequivocal diagnosis of adenocarcinoma. Using these strict cytological criteria
      would have eliminated these false-positive diagnoses.

PMID- 27889760
TI  - Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but
      Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats.
AB  - BACKGROUND: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms
      that are involved in cardiotoxicity are ambiguous, new methods for attenuating
      cardiotoxicity are needed. Recent studies have shown that bisphosphonates can
      decrease oxidative stress. Therefore, the objective of this study was to evaluate
      the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity.
      METHODS: Sixty-four male Wistar rats were allocated into four groups: the control
      group (C), the pamidronate group (P), the doxorubicin group (D) and the
      doxorubicin/pamidronate group (DP). The rats in the P and DP groups received
      pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP
      groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after
      doxorubicin injection, the rats were killed. Echocardiography, isolated heart
      study and biochemical analysis were performed. RESULTS: Doxorubicin-induced acute
      cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation,
      oxidative damage and induced alterations in myocardial energetic metabolism.
      Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and
      improved myocardial energetic metabolism. Regarding cardiac function, the DP
      group exhibited a decrease in the left ventricular ejection fraction in the
      echocardiography and a decrease in +dP/dt in the isolated heart study compared
      with other groups. The same DP group presented serum hypocalcaemia. CONCLUSIONS:
      Despite its ability to reduce oxidative stress and improve energy metabolism in
      the heart, pamidronate worsened systolic function in rats treated with
      doxorubicin, and therefore we cannot recommend its use in conjunction with
      anthracycline chemotherapy.

PMID- 27889761
TI  - Cilostazol Suppresses IL-23 Production in Human Dendritic Cells via an AMPK
      Dependent Pathway.
AB  - BACKGROUND/AIMS: Cilostazol has been previously demonstrated to inhibit IL-23
      production in human synovial macrophages via a RhoA/ROCK-dependent pathway.
      However, whether cilostazol affects IL-23 production in human dendritic cells
      remains largely unknown. The present study was designed to investigate this
      question and elucidate the possible underlying mechanisms. METHODS: Human
      monocyte-derived dendritic cells (mo-DCs) were pretreated with or without
      cilostazol and then incubated with zymosan. Enzyme-linked immunosorbent assay
      (ELISA) and real time PCR analyses were used to measure IL-23 protein expression
      and RNA levels, respectively, whereas Western blotting was used to measure the
      expression and phosphorylation level of AMPK. RESULTS: Our results demonstrated
      that cilostazol suppressed zymosan-induced IL-23 protein production in a
      concentration dependent manner without affecting dendritic cell viability. In
      addition, it was found that cilostazol suppressed the expression of the p19 and
      p40 subunits of IL-23. Moreover, cilostazol mimicked the effect of the AMPK
      agonist A-769662, as demonstrated by the fact that IL-23 production was also
      inhibited by A-769662, and the effect of cilostazol on IL-23 production was
      blocked by the AMPK antagonist Compound C. More importantly, Western blotting
      demonstrated that cilostazol led to an increased phosphorylation of AMPK.
      CONCLUSION: Collectively, our data suggest that cilostazol inhibits the
      production of IL-23 in human mo-DCs, potentially via the activation of AMPK. This
      suggests that cilostazol could be an effective anti-inflammatory agent in IL-23-
      and dendritic cell-related diseases.

PMID- 27889762
TI  - Evaluation of Isolation Methods for Circulating Tumor Cells (CTCs).
AB  - BACKGROUND: Detection of CTCs is a poor prognostic factor for many cancer types;
      however, their very low frequency represents an obstacle for their detection. The
      objective of the current study was to compare the performance of commonly used
      methods for CTCs isolation. METHODS: The evaluated methods using spiking
      experiments of MCF7, SKBR3 and MDA MB-231 breast cancer cell lines were (i)
      ficoll density gradient separation (DGS), (ii) red blood cell lysis
      (Erythrolysis) isolation, (iii) positive immunomagnetic selection (EpCAM Dynal
      beads), (iv) two different negative immunomagnetic separation systems (Dynal vs
      Miltenyi CD45 beads) as well as (v) the Cell Search platform and (vi) the ISET
      system. RESULTS: The recovery rates of Erythrolysis and DGS were 39% and 24%,
      respectively. Magnetic isolations are ranked from the worse to the best recovery
      rate as follows:, Myltenyi-anti-CD45 microbeads (24%); Dynal-anti-EpCAM beads
      (75%); Dynabeads-anti-CD45 (97%). CTCs isolation from blood samples using the
      CellSearch and ISET systems revealed that the recovery rate for Cell Search and
      ISET was 52% and 95%, respectively. CONCLUSIONS: Dynal-anti-CD45 beads have the
      best recovery rate compared to other magnetic methods. Furthermore the recovery
      rate of ISET was higher compared to Cell Search, especially for the more
      aggressive MDA-MB 231 cell line.

PMID- 27889763
TI  - Inhibition of the JAK2/STAT3/SOSC1 Signaling Pathway Improves Secretion Function
      of Vascular Endothelial Cells in a Rat Model of Pregnancy-Induced Hypertension.
AB  - BACKGROUND/AIMS: The present study aimed to investigate the effects of the
      JAK2/STAT3/SOSC1 signaling pathway on the secretion function of vascular
      endothelial cells (VECs) in a rat model of pregnancy-induced hypertension (PIH).
      METHODS: A PIH rat model was established. Forty-eight pregnant Sprague-Dawley
      female rats were selected and assigned into four groups: the normal group (normal
      non-pregnant rats), the non-PIH group (pregnant rats without PIH), the PIH group
      (pregnant rats with PIH) and the AG490 group (pregnant rats with PIH treated with
      AG490). Systolic blood pressure (SBP) and urinary protein (UP) were measured. The
      expressions of JAK2/STAT3/SOSC1 signaling pathway-related proteins in placenta
      tissues were detect by Western blotting. Radioimmunoassay was applied to detect
      serum levels of nitric oxide (NO), super oxide dismutase (SOD), placental growth
      factor (PGF), thromboxane B2 (TXB2) and endothelin (ET). Enzyme-linked
      immunosorbent assay (ELISA) was used to determine serum levels of interleukin-6
      (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-alpha).
      RESULTS: Compared with the normal and non-PIH groups, the PIH and AG490 groups
      had higher SBP and UP levels at 17th and 25th day of pregnancy. The expressions
      of p/t-JAK2, p/t-STAT3 and SOSC1 in the PIH and AG490 groups were higher than
      those in the non-PIH group, while the expressions of p/t-JAK2, p/t-STAT3 and
      SOSC1 in the AG490 group were lower than those in the PIH group. Compared with
      the non-PIH group, serum levels of ET, TXB2, IL-6 and TNF-alpha were increased in
      the PIH and AG490 groups, while serum levels of NO, SOD, 6-keto-PGF1a and IL-10
      levels were reduced. Furthermore, the AG490 had lower serum levels of ET, TXB2,
      IL-6 and TNF-alpha and higher serum levels of NO, SOD, 6-keto-PGF1a and IL-10
      than those in the PIH group. CONCLUSION: Our study provides evidence that
      inhibition of the JAK2/STAT3/SOSC1 signaling pathway could improve the secretion
      function of VECs in PIH rats.

PMID- 27889764
TI  - High Uric Acid Activates the ROS-AMPK Pathway, Impairs CD68 Expression and
      Inhibits OxLDL-Induced Foam-Cell Formation in a Human Monocytic Cell Line, THP-1.
AB  - BACKGROUND/AIMS: Hyperuricemia is part of the metabolic-syndrome cluster of
      abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia,
      and hypertension. Monocytes/macrophages are critical in the development of
      metabolic syndrome, including gout, obesity and atherosclerosis. However, how
      high uric acid (HUA) exposure affects monocyte/macrophage function remains
      unclear. In this study, we investigated the molecular mechanism of HUA exposure
      in monocytes/macrophages and its impact on oxidized low-density lipoprotein
      (oxLDL)-induced foam-cell formation in a human monocytic cell line, THP-1.
      METHODS: We primed THP-1 cells with phorbol-12-myristate-13-acetate (PMA) for
      differentiation, then exposed cells to HUA and detected the production of
      reactive oxygen species (ROS) and analyzed the level of phospho-AMPKalpha. THP-1
      cells were pre-incubated with Compound C, an AMPK inhibitor, or N-acetyl-L
      cysteine (NAC), a ROS scavenger, or HUA before PMA, to assess CD68 expression and
      phospho-AMPKalpha level. PMA-primed THP-1 cells were pre-treated with oxLDL
      before Compound C and HUA treatment. Western blot analysis was used to examine
      the levels of phospho-AMPKalpha, CD68, ABCG1, ABCA1, cyclooxygenase-2 (COX-2) and
      NF-kappaB (p65). Flow cytometry was used to assess ROS production and CD68
      expression in live cells. Oil-red O staining was used to observe oxLDL uptake in
      cells. RESULTS: HUA treatment increased ROS production in PMA-primed THP-1 cells;
      NAC blocked HUA-induced oxidative stress. HUA treatment time-dependently
      increased phospho-AMPKalpha level in PMA-primed THP-1 cells. The HUA-induced
      oxidative stress increased phospho-AMPKalpha levels, which was blocked by NAC.
      HUA treatment impaired CD68 expression during cell differentiation by activating
      the AMPK pathway, which was reversed by Compound C treatment. Finally, HUA
      treatment inhibited oxLDL uptake in the formation of foam cells in THP-1 cells,
      which was blocked by Compound C treatment. HUA treatment significantly increased
      the expression of ABCG1 and reversed the oxLDL-reduced ABCG1 expression but did
      not affect the expression of ABCA1, NF-kappaB (p65) or COX-2. CONCLUSIONS: HUA
      exposure activated the ROS-AMPK pathway, impaired CD68 expression, and inhibited
      oxLDL-induced foam-cell formation in a human monocytic cell line, THP-1.

PMID- 27889765
TI  - Contribution of Common Variants in GABRG2, RELN and NRG3 and Interaction Networks
      to the Risk of Hirschsprung Disease.
AB  - BACKGROUND: Hirschsprung disease (HSCR) is a complex and heterogeneous disorder,
      characterized by a deficit in enteric nervous system. Genome-wide studies implied
      GABRG2, RELN and NRG3 might be involved in HSCR etiology. Here, we aimed to
      assess genetic variants in GABRG2, RELN and NRG3 that may confer susceptibility
      to HSCR and explore genetic interaction networks in HSCR. METHODS: Using a
      strategy that combined case-control study and gene-gene interaction analysis with
      the MassArray system, we evaluated 24 polymorphisms within GABRG2, RELN and NRG3
      in 104 HSCR cases and 151 normal controls of Han Chinese origin. RESULTS: We
      observed that seven polymorphisms showed statistically significant differences
      between HSCR subjects and normal controls. For each of the three genes, the
      haplotypes which combined eight markers were the most significant. Moreover, we
      recruited SNPsyn, GO enrichment and MDR analyses to interrogate the interactions
      among GABRG2, RELN, NRG3 and our previous identified PTCH1 gene. Significant
      interaction networks were found among GABRG2, RELN, and PTCH1. CONCLUSION: We
      provide a first indication that common variants of GABRG2, RELN and NRG3 and the
      GABRG2-RELN-PTCH1 interaction networks might confer altered susceptibility to
      HSCR in the Han Chinese population, suggesting a potential mechanism underlying
      HSCR pathogenesis.

PMID- 27889766
TI  - Telencephalic Neuronal Activation Associated with Spatial Memory in the
      Terrestrial Toad Rhinella arenarum: Participation of the Medial Pallium during
      Navigation by Geometry.
AB  - Amphibians are central to discussions of vertebrate evolution because they
      represent the transition from aquatic to terrestrial life, a transition with
      profound consequences for the selective pressures shaping brain evolution.
      Spatial navigation is one class of behavior that has attracted the interest of
      comparative neurobiologists because of the relevance of the medial
      pallium/hippocampus, yet, surprisingly, in this regard amphibians have been
      sparsely investigated. In the current study, we trained toads to locate a water
      goal relying on the boundary geometry of a test environment (Geometry-Only) or
      boundary geometry coupled with a prominent, visual feature cue (Geometry
      Feature). Once learning had been achieved, the animals were given one last
      training session and their telencephali were processed for c-Fos activation.
      Compared to control toads exposed to the test environment for the first time,
      geometry-only toads were found to have increased neuronal labeling in the medial
      pallium, the presumptive hippocampal homologue, while geometry-feature toads were
      found to have increased neuronal labeling in the medial, dorsal, and lateral
      pallia. The data indicate medial pallial participation in guiding navigation by
      environmental geometry and lateral, and to a lesser extent dorsal, pallial
      participation in guiding navigation by a prominent visual feature. As such,
      participation of the medial pallium/hippocampus in spatial cognition appears to
      be a conserved feature of terrestrial vertebrates even if their life history is
      still tied to water, a brain-behavior feature seemingly at least as ancient as
      the evolutionary transition to life on land.

PMID- 27889767
TI  - Crocetin Inhibits Lipopolysaccharide-Induced Inflammatory Response in Human
      Umbilical Vein Endothelial Cells.
AB  - BACKGROUND/AIM: Crocetin is a readily bioavailable and bioactive compound
      extracted from Saffron. Previous studies indicated its various biomedical
      properties including antioxidant and anti-coagulation potencies. However, its
      effect on inflammation, notably within the cardiovascular system, has not been
      investigated yet. In the present study, we utilized human umbilical vein
      endothelial cell (HUVEC) to elucidate the effect of Crocetin on vascular
      inflammation. METHODS: Cell viability and toxicity were evaluated by MTT and
      Lactate dehydrogenase (LDH) assay, respectively. Pro-inflammatory chemokine
      <under>M</under>onocyte Chemoattractant <under>P</under>rotein-1 (MCP-1) and
      <under>I</under>nter<under>l</under>eukin-8 (IL-8) expressions were determined by
      RT-PCR and ELISA. With fluorescence labeled U937 cells, we examined immune cell
      adhesion to the inflamed HUVEC in vitro, which was further confirmed by the H&E
      staining in the murine subcutaneous endothelium in vivo. RESULTS: Upon
      Lipopolysaccharide (LPS)-induced inflammatory response in HUVECs, Crocetin
      ameliorated cell cytotoxicity, suppressed MCP-1 and IL-8 expressions through
      blocking NF-kappaB p65 signaling transduction. Moreover, Crocetin inhibited
      immune cells adhesion and infiltration to inflamed endothelium, which is a key
      step in inflammatory vascular injury. CONCLUSIONS: These findings suggest that
      Crocetin, a natural herb extract, is a potent suppressor of vascular endothelial
      inflammation.

PMID- 27889768
TI  - Clinical Utility of Serum Cystatin C in Predicting Diabetic Nephropathy Among
      Patients with Diabetes Mellitus: a Meta-Analysis.
AB  - BACKGROUND/AIMS: Clinically, there is lack of predictors for diabetic nephropathy
      (DN) in diabetes mellitus (DM) without microalbuminuria, macroalbuminuria or
      retinopathy. METHODS: PubMed, Chinese Biomedical Database, Cochrane Library,
      EMBASE and Elsevier Database were searched from inception to August 13, 2016.
      Studies involving patients with DM and containing data on cystatin C measurements
      and the measured glomerular filtration rate (mGFR) were included. Pooled
      sensitivity, specificity, positive predictive value, negative predictive value
      and other diagnostic indices were evaluated using a random effect model. RESULTS:
      The meta-analysis enrolled 9 studies with 1417 patients. The pooled sensitivity
      and specificity of serum cystatin C for predicting DN were 0.88 (95% CI 0.85 -
      0.91) and 0.85 (95% CI 0.82 - 0.87), respectively. The pooled positive and
      negative predictive values of serum cystatin C for predicting DN were 7.04 (95%
      CI 4.33 - 11.43) and 0.13 (95% CI 0.09 - 0.20), respectively. The area under the
      summary receiver operating characteristic (SROC) curve was 0.9549, and the
      diagnostic odds ratio was 66.80 (95% CI 27.92 - 159.86). CONCLUSION: Serum
      cystatin C is an early predictor of DN among patients with DM.

PMID- 27889769
TI  - Immunohistochemical Heterogeneity of the Endothelium of Blood and Lymphatic
      Vessels in the Developing Human Liver and in Adulthood.
AB  - The endothelium of liver sinusoids in relation to the endothelium of other blood
      vessels has specific antigen expression similar to the endothelium of lymphatic
      vessels. Bearing in mind that there is no consensus as to the period or intensity
      of the expression of certain antigens in the endothelium of blood and lymphatic
      vessels in the liver, the aim of our study was to immunohistochemically
      investigate the dynamic patterns of the expression of CD31, CD34, D2-40, and LYVE
      1 antigens during liver development and in adulthood on paraffin tissue sections
      of human livers of 4 embryos, 38 fetuses, 6 neonates, and 6 adults. The results
      show that, in a histologically immature liver at the end of the embryonic period,
      CD34 molecules are expressed only on vein endothelium localized in developing
      portal areas, whereby the difference between portal venous branches and CD34
      negative central veins belongs to the collecting venous system. In the fetal
      period, with aging, expression of CD34 and CD31 molecules on the endothelium of
      central veins and blood vessels of the portal areas increases. Sinusoidal
      endothelium shows light and sporadic CD34 immunoreactivity in the late embryonic
      and fetal periods, and is lost in the neonatal and adult periods, unlike CD31
      immunoreactivity, which is poorly expressed in the fetal and neonatal periods but
      is present in adults. The endothelium of sinusoids and lymphatic vessels express
      LYVE-1, and the endothelium of lymphatic vessels express LYVE-1 and D2-40 but not
      CD34. Similarity between the sinusoidal and lymphatic endothelium includes the
      fact that both types are LYVE-1 positive and CD34 negative.

PMID- 27889770
TI  - Usefulness of Discriminability and Response Bias Indices for the Evaluation of
      Recognition Memory in Mild Cognitive Impairment and Alzheimer Disease.
AB  - BACKGROUND: Most studies examining episodic memory in Alzheimer disease (AD) have
      focused on patients' impaired ability to remember information. This approach
      provides only a partial picture of memory deficits since other factors involved
      are not considered. OBJECTIVE: To evaluate the recognition memory performance by
      using a yes/no procedure to examine the effect of discriminability and response
      bias measures in amnestic mild cognitive impairment (a-MCI), AD dementia, and
      normal-aging subjects. METHODS: We included 43 controls and 45 a-MCI and 51 mild
      AD dementia patients. Based on the proportions of correct responses (hits) and
      false alarms from the Rey Auditory Verbal Learning Test (RAVLT), discriminability
      (d') and response bias (C) indices from signal detection theory (SDT) were
      calculated. RESULTS: Results showed significant group differences for d' (F (2) =
      83.26, p < 0.001), and C (F (2) = 6.05, p = 0.00). The best predictors of group
      membership were delayed recall and d' scores. The d' measure correctly classified
      subjects with 82.98% sensitivity and 91.11% specificity. CONCLUSIONS: a-MCI and
      AD dementia subjects exhibit less discrimination accuracy and more liberal
      response bias than controls. Furthermore, combined indices of delayed recall and
      discriminability from the RAVLT are effective in defining early AD. SDT may help
      enhance diagnostic specificity.

PMID- 27889771
TI  - CD44 and CD44v6 are Correlated with Gastric Cancer Progression and Poor Patient
      Prognosis: Evidence from 42 Studies.
AB  - BACKGROUND/AIMS: The prognostic power of the levels of total CD44 and its isoform
      CD44v6 for patients with gastric cancer (GC) remains controversial. Therefore,
      our study aims to generalize the clinicopathological and prognostic significance
      of these two proteins in GC. METHODS: A literature search of the PubMed, Web of
      Science and Embase databases was conducted to identify eligible studies. The odds
      ratio (OR) with a 95% confidence interval (CI) was used to assess the effects.
      RESULTS: In all, 42 studies including 6,229 patients were included in this
      analysis. Total CD44 was mentioned in 21 papers, and the results showed that CD44
      was positively correlated with the T category, the N category, distant
      metastasis, lymphatic invasion and TNM stage. Moreover, patients with CD44
      overexpression had a lower 5-year overall survival (OS) rate (OR = 3.35, 95%CI =
      1.83-6.13). CD44v6 was mentioned in 24 studies, with results that were similar to
      those for total CD44. However, total CD44 or CD44v6 expression was not correlated
      with tumor size and histological grade. CONCLUSION: High CD44 or CD44v6
      expression levels were correlated with cancer progression and poor prognosis in
      patients with GC. Both CD44 and CD44v6 may be useful diagnostic or prognostic
      biomarkers for GC.

PMID- 27889772
TI  - Sonodynamic Therapy Inhibits Fibrogenesis in Rat Cardiac Fibroblasts Induced by
      TGF-beta1.
AB  - BACKGROUND/AIMS: Sonodynamic therapy (SDT) is a localized ultrasound-activated
      therapy for atherosclerosis when combined with a sonosensitizer, 5-aminolevulinic
      acid (ALA), but whether it can prevent cardiac fibrosis has not been studied. In
      the present study, we evaluated the effects SDT on fibrogenesis in rat cardiac
      fibroblasts. METHODS: The primary cardiac fibroblasts were isolated from rats,
      and induced to fibrogenesis with TGF-beta1. With this in vitro model, we tested
      the preventive effects of SDT on fibrogenesis and further the underlying
      mechanism. RESULTS: TGF-beta1 stimulation up-regulated alpha-SMA and COLI/III
      protein levels in cardiac fibroblasts, and enhanced the progression of cells from
      the G0/G1 phase to the S phase. SDT inhibited the TGF-beta1 mediated cell
      proliferation and decreased the levels of alpha-SMA and COLI/III by activating
      AKT/GSK3beta pathway and blocking TGF-beta1/SMAD3 signaling. CONCLUSION: Our
      studies demonstrate an antifibrotic effect of SDT in rat cardiac fibroblasts,
      suggesting that SDT may intervene cardiac fibrogenesis by regulating myocardial
      fibrotic remodeling.

PMID- 27889773
TI  - Evaluation of KIM-1 and NGAL as Early Indicators for Assessment of Gentamycin
      Induced Nephrotoxicity In Vivo and In Vitro.
AB  - BACKGROUND/AIMS: The aminolycoside Gentamicin is a widely used antibiotic,
      applied in equine medicine. Despite its clinical use, concerns remain regarding
      the potential toxic side-effects, such as nephrotoxicity. Early detection of
      renal damage is critical in preclinical drug development. This study was aimed to
      determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase
      associated lipocalin (NGAL) may be early indicators in the assessment of
      Gentamycin-induced nephrotoxicity. METHODS: In our study, a model of Gentamicin
      induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50
      or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal
      toxicity during the progression of acute kidney injury (AKI). Additionally,
      biomarkers were assessed in human kidney proximal epithelial cells (HK-2) treated
      with Gentamicin for 2, 6, 12, 24, 36 or 48h in vitro. RESULTS: Repeated
      administration of Gentamicin to rats for 1, 3, or 7 days resulted in a dose- and
      time-dependent increase in the expression of KIM-1 and NGAL. The expressions of
      the two biomarkers changed prior to renal tubule damage and increases in serum
      creatinine (SCr) and blood urea nitrogen (BUN) levels, suggesting their
      usefulness for predicting Gentamicin-induced acute kidney injury (AKI) in vivo.
      CONCLUSIONS: In contrast, no significant increase in the expression of the
      biomarker genes and proteins were evident in HK-2 cells after treated by
      Gentamycin for up to 48h, suggesting that they may not be suitable endpoints for
      sensitive detection of nephrotoxic effects in vitro.

PMID- 27889774
TI  - Stimulation of Suicidal Erythrocyte Death by the CDC25 Inhibitor NSC-95397.
AB  - BACKGROUND/AIMS: The CDC25B inhibitor NSC-95397 triggers apoptosis of tumor cells
      and is thus considered for the treatment of malignancy. The substance is
      effective in part by modification of gene expression. Similar to apoptosis of
      nucleated cells erythrocytes may undergo eryptosis, the suicidal erythrocyte
      death characterized by cell shrinkage and cell membrane scrambling with
      phosphatidylserine translocation to the erythrocyte surface. Eryptosis may be
      triggered by increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress,
      ceramide, as well as activation of protein kinases. The present study explored,
      whether NSC-95397 induces eryptosis and, if so, to shed some light on the
      mechanisms involved. METHODS: Phosphatidylserine exposure at the cell surface was
      estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from
      Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence, and ceramide
      abundance utilizing specific antibodies. RESULTS: A 48 hours exposure of human
      erythrocytes to NSC-95397 significantly increased the percentage of annexin-V
      binding cells (>= 1 uM), significantly decreased forward scatter (>= 2.5 uM), and
      significantly increased Fluo3-fluorescence (>= 1 uM), DCFDA fluorescence (5 uM)
      and ceramide abundance (>= 5 uM). The effect of NSC-95397 (5 uM) on annexin-V
      binding was slightly, but significantly blunted by removal of extracellular Ca2+
      and by addition of the protein kinase C inhibitor staurosporine (1 uM).
      CONCLUSIONS: NSC-95397 triggers cell shrinkage and phospholipid scrambling of the
      erythrocyte cell membrane, an effect in part requiring entry of Ca2+ and
      activation of staurosporine sensitive kinase(s).

PMID- 27889775
TI  - Vitamin D Receptor TaqI Gene Polymorphism and Dental Caries in Czech Children.
AB  - AIM: We analyzed the VDR TaqI (rs731236) gene polymorphism in children with and
      those without dental caries. METHODS: A total of 388 subjects, 153 caries-free
      (with decayed/missing/filled teeth [DMFT] = 0) and 235 children with dental
      caries (DMFT >=1), were genotyped by the TaqMan method. RESULTS: Although no
      significant differences in VDR TaqI allele and genotype frequencies between
      caries-free and caries-affected children were detected, a significant association
      between this polymorphism and gingivitis was found (p < 0.05). CONCLUSIONS: In
      contrast to previous studies from China and Turkey, the VDR TaqI gene variant
      cannot be used as a marker for identification of Czech children with increased
      dental caries risk.

PMID- 27889776
TI  - Cinnamic Acid (CINN) Induces Apoptosis and Proliferation in Human Nasopharyngeal
      Carcinoma Cells.
AB  - BACKGROUND/AIMS: CINN is the main ingredient of the traditional Chinese medicine
      cinnamon. The purpose of the present study was to investigate the effects of CINN
      on the proliferation and apoptosis of NPC cells and to elucidate the underlying
      molecular mechanisms. MATERIALS AND METHODS: CNE2 human NPC cells were treated
      with various CINN concentrations. The effects of CINN on the proliferation and
      apoptosis of CNE2 NPC cells were examined using the MTT assay and flow cytometric
      analysis. Additionally, western blotting was performed to analyze the expression
      of a number of cell cycle- and apoptosis-related proteins. RESULTS: The
      proliferation of CNE2 cells was significantly inhibited after treatment with
      different CINN concentrations for various lengths of time. The inhibitory effect
      of CINN was concentration-and time-dependent. Flow cytometric analysis showed
      that 2 mmol/L CINN displayed a significant apoptosis-inducing effect. The western
      blot analysis results showed that KLF6, Fas-L, Bax, P53 and caspase-3 protein
      expression was drastically increased in the CNE2 cells after treatment with 2
      mmol/L CINN, whereas Bcl-2 and cyclin D1 protein expression was markedly reduced.
      CONCLUSION: CINN inhibits the proliferation and induces the apoptosis of CNE2
      cells. Therefore, CINN possesses a potential anti-tumor effect.

PMID- 27889777
TI  - Sodium Pentosan Polysulfate Reduced Renal Ischemia-Reperfusion-Induced Oxidative
      Stress and Inflammatory Responses in an Experimental Animal Model.
AB  - Acute kidney injury (AKI) remains an independent risk factor for mortality and
      morbidity after vascular surgery (affecting the renal arteries) or aortic surgery
      (requiring suprarenal aortic clamping). These types of vascular surgery produce
      renal ischemia/reperfusion (I/R) injury, a common cause of AKI. The present
      studies aimed at monitoring the course of renal I/R injury at the cellular level
      and investigating the efficacy of long-term preoperative and single-shot
      intraoperative administration of sodium pentosan polysulfate (PPS) to protect
      renal tissue from acute I/R injury both in native and diabetic kidneys in rats.
      Western blot analyses of the proapoptotic (bax) and antiapoptotic (bcl-2)
      signaling pathways, as well as the extent of DNA damage (phospho-p53), were
      performed. Oxidative stress followed upon the termination of malondialdehyde,
      reduced glutathione, thiol group, and superoxide dismutase plasma levels.
      Inflammatory changes were measured by the determination of serum tumor necrosis
      factor-alpha and interleukin-1 levels. Morphological changes were detected by
      histological examinations. Our results showed that the long-term administration
      of PPS has an advantage in reducing I/R kidney injury in diabetic rats, while
      high-dose, single-shot parenteral administration of PPS prior to
      revascularization might be useful in nondiabetic rats.

PMID- 27889778
TI  - Primary Intestinal Hodgkin Lymphoma Mimicking Intraabdominal Abscess in a Renal
      Transplant Recipient: A Case Report.
AB  - INTRODUCTION: Post-transplant lymphoproliferative disease (PTLD) comprises a
      variety of lymphoid and plasma cell disorders arising in patients with a solid
      organ transplant. Monomorphic lymphomas represent the most significant part of
      this wide spectrum, with the overall risk rising with the aggressiveness of
      lymphoid proliferation in comparison to the general population. The development
      of Hodgkin lymphoma is very rare in transplant recipients, comprising less than
      6% of all monomorphic PTLD, while cases of primary intestinal Hodgkin lymphoma in
      these circumstances are anecdotal. CASE REPORT: We describe an exceptional case
      of intestinal Hodgkin lymphoma mimicking an intra-abdominal abscess that
      developed in a transplant recipient 19 years after kidney transplantation. By
      presenting this case, we wish to emphasize the importance of suitable diagnostic
      pathways in transplant recipients experiencing prolonged fever episodes or masses
      of unknown origin, thus raising the awareness of possible PTLD development in
      such patients. CONCLUSION: The lack of information about transplant recipients
      with Hodgkin PTLD regarding the site of involvement and type of treatment
      suggests the necessity of conducting larger international studies aimed at
      providing further insight into this particular group of patients.

PMID- 27889779
TI  - Tanshinone IIA Affects Autophagy and Apoptosis of Glioma Cells by Inhibiting
      Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling
      Pathway.
AB  - OBJECTIVE: To test the effects of Tanshinone IIA (Tan IIA) on cell viability,
      cycle, apoptosis, and autophagy of human glioma cell U251 by regulating
      phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)
      signal pathway. METHODS: Tan IIA and PI3K agonist (740 Y-P) were used to treat
      glioma cells U251. MTT assay was used to assess cell viability and flow cytometry
      was used to detect cell apoptosis and cell cycle. The expressions of apoptosis
      related proteins (Bcl-2 and Bax), autophagy-related proteins (LC3B and Beclin 1)
      and PI3K/Akt/mTOR signal pathway-associated proteins (p-PI3K, p-Akt and p-mTOR)
      were evaluated by Western blotting. RESULTS: Tan IIA decreased the expression of
      p-PI3K and p-Akt proteins, inhibited cell viability and promoted apoptosis.
      Meanwhile, the expression of Bax increased, while the expression of Bcl-2
      decreased. In addition, Tan IIA promoted autophagy in U251 glioma cells and
      raised the expression of LC3B and Beclin 1. However, 740 Y-P played a reversed
      role of Tan IIA in cell viability, cycle, apoptosis, and autophagy of U251 cells.
      CONCLUSION: Tan IIA could suppress the viability of U251 cells and induce cell
      apoptosis and autophagy, which might be related to the inhibition of the
      PI3K/Akt/mTOR signal pathway.

PMID- 27889780
TI  - Targeted Treatment of Esophagogastric Cancer.
AB  - Adenocarcinoma of the esophagogastric junction (EGJ) and stomach remains one of
      the most common causes of cancer-related death worldwide. Although there is
      increasing data on the mutational landscape of esophagogastric cancer, phase III
      trials often yield negative results, and there is a paucity of approved targeted
      agents. For the time being, the subset of patients carrying HER2-positive
      metastatic tumors can receive trastuzumab in addition to chemotherapy.
      Furthermore, ramucirumab has been found to be active both as a single agent and
      in combination with paclitaxel. Herein, we give an overview of currently approved
      targeted treatments for locally advanced/resectable as well as
      unresectable/metastatic EGJ/gastric adenocarcinoma, summarizing the underlying
      clinical studies. Moreover, further potential targets still under investigation
      are presented.

PMID- 27889781
TI  - Striated Muscle in Radical Prostatectomy Specimens: A Marker of Apical Dissection
      Quality and an Independent Predictor of Urinary Continence after Endoscopic
      Extraperitoneal Radical Prostatectomy.
AB  - INTRODUCTION: The study aimed to determine if the presence and amount of striated
      muscle on the apical sections of the cruciate sections of laparoscopic radical
      prostatectomy (LRP) specimens predict early and long-term urinary continence
      outcomes. PATIENTS AND METHODS: We conducted a retrospective review of our
      prospectively collected single surgeon LRP database. We identified patients based
      on their continence outcomes (continent (0 pads) or incontinent at 12 months),
      with an approximate even spread early continent and incontinent patients). An
      uropathologist separate from the urology team was blinded to outcome and assessed
      each patients' apical cruciate sections (H&E stained) for the presence,
      percentage and maximal diameter of muscle and extraprostatic tissue on these
      sections. Specifically 2 scoring systems were used: (1) semi-quantitative
      estimation of percentage of muscle on the apical cruciate sections (low <5% and
      high >5%) and (2) percentage of total extraprostatic tissue on cruciate section
      (low <10% and high >10%). Logistic regression and classification and regression
      tree analyses were performed to identify the predictors of urinary incontinence
      (UI). RESULTS: In total 80 patients were analyzed, 38 were continent and 42 were
      incontinent at 12 months follow-up. The percentage of extraprostatic
      tissue/muscle being an independent predictor of being wet at 12 months (p =
      0.002) on multivariate regression along with age (p = 0.04). Using percentage of
      extraprostatic tissue in cruciate section (high >10%) to predict UI at 12 months,
      it yielded 71% sensitivity, 82% specificity, 81% PPV, 72% NPV and 76% accuracy.
      CONCLUSION: The use of simple additional reporting of muscle and extraprostatic
      tissue on the apical sections of RP specimens can help to better predict the
      likelihood of continence return.

PMID- 27889782
TI  - Molecular Pathology: A Requirement for Precision Medicine in Cancer.
AB  - The increasing importance of targeting drugs and check-point inhibitors in the
      treatment of several tumor entities (breast, colon, lung, malignant melanoma,
      lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS,
      EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for
      surgical pathology. Since almost all the biomarkers to be specifically detected
      are tissue based, a precise and reliable diagnostic is absolutely crucial. To
      meet this challenge surgical pathology has adapted a number of molecular methods
      (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR
      and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing
      (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc.) to
      be applicable for formalin-fixed paraffin-embedded tissue. Reading a patient's
      tissue as 'deeply' as possible and obtaining information on the morphological,
      genetic, proteomic and epigenetic background are the tasks of pathologists and
      molecular biologists and provide the clinicians with information relevant for
      precision medicine. Intensified cooperation between clinicians and pathologists
      will provide the basis of improved clinical drug selection and guide development
      of new cancer gene therapies and molecularly targeted drugs by research units and
      the pharmaceutical industry.

PMID- 27889783
TI  - Advances in Cancer Therapy: Targeted Therapies.

PMID- 27889784
TI  - Targeted Therapy of CLL.
AB  - The landscape of chronic lymphocytic leukemia (CLL) has undergone profound
      changes in the past years. First, the addition of CD20-targeting antibodies to
      conventional chemotherapy has improved the therapeutic outcome in the majority of
      CLL patients. Since the establishment of the critical role of the B cell receptor
      signaling pathway in the pathogenesis of CLL, several agents have been developed
      to target this pathway. Ibrutinib and idelalisib, 2 potent kinase inhibitors,
      have both become available for CLL therapy in the first and second line.
      Additionally, the observation of high expression levels of the anti-apoptotic
      mitochondrial protein Bcl-2 in CLL has led to the development of venetoclax, a
      BH3 mimetic compound that inhibits Bcl-2 and has shown high efficacy in CLL. This
      short review summarizes preclinical and clinical data on currently available
      agents in CLL and provides an outlook on upcoming new challenges in the targeted
      therapy of CLL.

PMID- 27889785
TI  - Overcoming Cost Implications of Mutational Analysis in Patients with
      Gastrointestinal Stromal Tumors: A Pragmatic Approach.
AB  - BACKGROUND: Genetic analysis of tissue derived from patients with advanced
      gastrointestinal stromal tumors (GISTs) is not uniformly applied on a national
      and international level, even though mutational data can provide clinically
      relevant prognostic and predictive information, especially in patients qualifying
      for treatment with expensive targeted agents. METHODS: The current article
      describes the rationale for genetic testing of GIST tissue, looks at financial
      implications associated with such analysis and speculates on potential cost
      savings introduced by routine mutational testing and tailored use of tyrosine
      kinase inhibitors based on genotyping. This work is based on a hypothetical
      analysis of epidemiological data, drug costs, reimbursement criteria and market
      research figures. RESULTS: The cost burden for routine genotyping of important
      genes in GISTs, especially in patients at high risk for relapse after primary
      surgery and in advanced, inoperable metastatic disease, is relatively low. The
      early identification of GISTs with primary resistance mutations should be the
      basis for personalized GIST treatment and reimbursement of drugs. As illustrated
      by Belgian figures, the exclusive use of a drug such as imatinib in patients who
      are likely to benefit from the agent based on genetic information can lead to
      significant cost savings, which outweigh the costs for testing. CONCLUSIONS:
      Mutational analysis of GIST should be considered early in all patients at risk
      for relapse after curative surgery and in the case of advanced, inoperable,
      metastatic disease. The costs for the actual genotyping should not be used as an
      argument against profiling of the tumor. The adjuvant and palliative systemic
      treatment of GISTs should be personalized based on the genotype and other known
      prognostic and predictive factors. Reimbursement criteria for essential agents
      such as imatinib should be adapted accordingly.

PMID- 27889786
TI  - Targeted Therapy of Colorectal Cancer.
AB  - Over the past decades, considerable progress has been made in the management of
      colorectal cancer (CRC), leading to a significant improvement in overall
      survival. Although part of this success has been rightly attributed to aggressive
      surgical management and advances in other adjunct treatments, our understanding
      of the pathogenesis of CRC and emergence of newer molecular targets for colon
      cancer has created a powerful impact. In this review article, we will discuss
      various targeted therapies in the management of metastatic CRC (mCRC). In
      particular, vascular endothelial growth factor (VEGF)- and epidermal growth
      factor receptor (EGFR)-targeting monoclonal antibodies have become integral
      components of the first-line treatment strategies for mCRC. Newer agents on the
      horizon soon to be incorporated in clinical practice will be briefly reviewed as
      well. Currently, the only predictive biomarker for treatment selection in
      patients with mCRC is tumor RAS mutational status.

PMID- 27889787
TI  - Stratified Treatment in Lung Cancer.
AB  - Even though great efforts have been made to improve chemotherapy-based treatment
      approaches for lung cancer, the prognosis of patients with advanced and
      metastasized disease remains particularly poor. In recent years, a growing number
      of genetic aberrations driving lung cancer have been identified. Targeted
      inhibition of some of these aberrations, most prominently mutated EGFR and ALK,
      by tyrosine kinase inhibitors has dramatically increased efficacy and
      tolerability of systemic lung cancer treatment in subsets of patients. However,
      the duration of response is limited due to the acquisition of molecular
      mechanisms of resistance to targeted treatment. Modern next-generation inhibitors
      aim to break resistance. A deep understanding of the mechanisms of treatment
      failure is imperative to the development of new approaches. In this review, we
      focus on the current status of stratified therapy in lung cancer and highlight
      new, potentially promising treatment approaches.

PMID- 27889788
TI  - Inhibition of Angiotensin-II Production Increases Susceptibility to Acute
      Ischemia/Reperfusion Arrhythmia.
AB  - BACKGROUND Myocardial ischemia and reperfusion lead to impairment of electrolyte
      balance and, eventually, lethal arrhythmias. The aim of this study was to
      investigate the effects of pharmacological inhibition of angiotensin-II (Ang-II)
      production on heart tissue with ischemia-reperfusion damage, arrhythmia, and
      oxidative stress. MATERIAL AND METHODS Rats were divided into 4 groups: only
      ischemia/reperfusion (MI/R), captopril (CAP), aliskiren (AL), and CAP+AL. The
      drugs were given by gavage 30 min before anesthesia. Blood pressure and
      electrocardiography (ECG) were recorded during MI/R procedures. The heart tissue
      and plasma was kept so as to evaluate the total oxidant (TOS), antioxidant status
      (TAS), and creatine kinase-MB (CK-MB). RESULTS Creatine kinase-MB was not
      different among the groups. Although TAS was not affected by inhibition of Ang-II
      production, TOS was significantly lower in the CAP and/or AL groups than in the
      MI/R group. Furthermore, oxidative stress index was significantly attenuated in
      the CAP and/or AL groups. Captopril significantly increased the duration of VT
      during ischemia; however, it did not have any effect on the incidence of
      arrhythmias. During reperfusion periods, aliskiren and its combinations with
      captopril significantly reduced the incidence of other types of arrhythmias.
      Captopril alone had no effect on the incidence of arrhythmias, but significantly
      increased arrhythmias score and durations of arrhythmias during reperfusion. MAP
      and heart rate did not show changes in any groups during ischemic and reperfusion
      periods. CONCLUSIONS Angiotensin-II production appears to be associated with
      elevated levels of reactive oxygen species, but Ang-II inhibitions increases
      arrhythmia, mainly by initiating ventricular ectopic beats.

PMID- 27889789
TI  - Effect of Natural Cycle Endometrial Preparation for Frozen-Thawed Embryo Transfer
      in Patients with Advanced Endometriosis.
AB  - BACKGROUND The aim of this study was to investigate the effect of natural cycle
      (NC) endometrial preparation for frozen-thawed embryo transfer (FET) in women
      with advanced endometriosis. MATERIAL AND METHODS This retrospective study
      included 179 patients with stage III-IV endometriosis who underwent 233 FET
      cycles at a tertiary care academic reproductive medical center between March 2011
      and August 2013 (group A). The control group included 258 patients with tubal
      factor infertility who underwent 300 FET cycles (group B). Both groups were
      prepared for FET using a NC protocol. Rates of implantation, clinical pregnancy,
      live birth, ongoing pregnancy, miscarriage, and pregnancy complication were
      recorded. RESULTS The implantation rate (A: 36.0%, B: 30.4%, P=0.06), the
      pregnancy rate (A: 50.2%, B: 45.3%, P=0.263), and the live birth rate (A: 39.91%,
      B: 39.0%, P=0.428) were similar between the stage III-IV endometriosis and tubal
      factor infertility groups. No differences were observed in ongoing rates of
      pregnancy, miscarriage, and pregnancy complications, independent of endometriosis
      severity. No congenital birth defects were found. When high-quality embryos are
      transferred, pregnancy results were not affected by active endometriosis.
      Although severe endometriosis did not affect birth rate, higher frequencies of
      premature delivery (mean gestational age A: 37 weeks, B: 38.3 weeks, P=0.044) and
      low birth weight were observed (<2500 g A: 26.4%, B: 16.6%, P=0.047). CONCLUSIONS
      There was no difference in pregnancy outcomes between patients with endometriosis
      and those with tubal infertility. Pregnancy outcomes in patients with
      endometriosis were not affected by endometriosis severity. Pregnancy outcomes
      were not affected by active endometrial cyst.

PMID- 27889790
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1080/14686996.2016.1140301.][This corrects the
      article DOI: 10.1080/14686996.2016.1140302.][This corrects the article DOI:
      10.1080/14686996.2016.1140303.][This corrects the article DOI:
      10.1080/14686996.2016.1140305.][This corrects the article DOI:
      10.1080/14686996.2016.1140306.][This corrects the article DOI:
      10.1080/14686996.2016.1140307.][This corrects the article DOI:
      10.1080/14686996.2016.1140308.][This corrects the article DOI:
      10.1080/14686996.2016.1145530.][This corrects the article DOI:
      10.1080/14686996.2016.1148528.].

PMID- 27889791
TI  - Erratum: Processing of polysiloxane-derived porous ceramics: a review.
AB  - [This corrects the article DOI: 10.1088/1468-6996/11/4/044303.].

PMID- 27889792
TI  - Corrigendum: A microfluidic paper-based electrochemical biosensor array for
      multiplexed detection of metabolic biomarkers (2013 Sci. Technol. Adv. Mater. 14
      054402).
AB  - [This corrects the article DOI: 10.1088/1468-6996/14/5/054402.].

PMID- 27889793
TI  - Corrigendum: Progress in thermomechanical control of steel plates and their
      commercialization.
AB  - [This corrects the article DOI: 10.1088/1468-6996/13/2/023001.].

PMID- 27889794
TI  - Corrigendum: A simple method for the quantification of molecular decorations on
      silica particles (2014 Sci. Technol. Adv. Mater. 15 015002).
AB  - [This corrects the article DOI: 10.1088/1468-6996/15/1/015002.].

PMID- 27889795
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1088/1468-6996/12/5/055009.].

PMID- 27889796
TI  - Corrigendum: Material design and structural color inspired by biomimetic
      approach.
AB  - [This corrects the article DOI: 10.1088/1468-6996/12/6/064709.].

PMID- 27889797
TI  - Erratum: Chemistry of layered d-metal pnictide oxides and their potential as
      candidates for new superconductors.
AB  - [This corrects the article DOI: 10.1088/1468-6996/9/3/033003.].

PMID- 27889798
TI  - Selective effect of cytokine-induced killer cells on survival of patients with
      early-stage melanoma.
AB  - Adoptive immunotherapy using cytokine-induced killer (CIK) cells has shown
      potential antitumor ability against several kinds of cancers, including melanoma.
      However, little is known about the achievable outcome of CIK cells in melanoma
      patients at different pathological stages. Here we recruited 55 patients treated
      with conventional therapy plus CIK cells as the CIK group, and 49 patients
      treated with conventional therapy alone as the control group. The pathological
      characteristics were comparable between two groups, with a follow-up period up to
      40 months. Survival data and immune responses were evaluated after CIK cell
      treatment. In this study, CIK cells were successfully generated from peripheral
      blood of melanoma patients after in vitro culture for 14 days. The cultured CIK
      cells not only produced high levels of pro-inflammatory cytokines upon in vitro
      stimulation but also efficiently killed human melanoma cell lines. No serious
      side events were observed in all patients treated with CIK cells. Furthermore,
      infusions of CIK cells improved the quality of life in some patients, including
      advanced cases. More importantly, the CIK group exhibited better survival rates
      compared to the control group among early-stage melanoma patients, in consistent
      with the increased frequency of peripheral CD4+ T cells. However, the patients
      with advanced-stage melanoma did not benefit from the CIK cell therapy in terms
      of survival rate. In conclusion, CIK cells combined with conventional treatments
      may prolong the survival of early-stage melanoma patients and improve the quality
      of life for some advanced cases in a safe way.

PMID- 27889799
TI  - A polymorphism in the promoter region of PD-L1 serves as a binding-site for SP1
      and is associated with PD-L1 overexpression and increased occurrence of gastric
      cancer.
AB  - PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical
      role in tumor immune escape. In this study, we found a polymorphism rs10815225 in
      the PD-L1 promoter region was significantly associated with the occurrence of
      gastric cancer. The GG homozygous frequency was higher in the cancer patients
      than that in the precancerous lesions, which was higher than that in the health
      controls. This polymorphism locates in the binding-site of Sp1 transcription
      factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer
      patients was apparently higher than that in the GC heterozygotes. Luciferase
      reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter
      instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and
      attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin
      immunoprecipitation results further confirmed the binding of SP1 to the promoter
      of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a
      functional polymorphism rs4143815 in the PD-L1 3'-UTR, and the haplotypes of
      these two polymorphisms were also markedly related to gastric cancer risk. These
      results revealed a novel mechanism underlying genetic polymorphisms influencing
      PD-L1 expression modify gastric cancer susceptibility.

PMID- 27889800
TI  - Polymorphism at expressed DQ and DR loci in five common equine MHC haplotypes.
AB  - The polymorphism of major histocompatibility complex (MHC) class II DQ and DR
      genes in five common equine leukocyte antigen (ELA) haplotypes was determined
      through sequencing of mRNA transcripts isolated from lymphocytes of eight ELA
      homozygous horses. Ten expressed MHC class II genes were detected in horses of
      the ELA-A3 haplotype carried by the donor horses of the equine bacterial
      artificial chromosome (BAC) library and the reference genome sequence: four DR
      genes and six DQ genes. The other four ELA haplotypes contained at least eight
      expressed polymorphic MHC class II loci. Next generation sequencing (NGS) of
      genomic DNA of these four MHC haplotypes revealed stop codons in the DQA3 gene in
      the ELA-A2, ELA-A5, and ELA-A9 haplotypes. Few NGS reads were obtained for the
      other MHC class II genes that were not amplified in these horses. The amino acid
      sequences across haplotypes contained locus-specific residues, and the locus
      clusters produced by phylogenetic analysis were well supported. The MHC class II
      alleles within the five tested haplotypes were largely non-overlapping between
      haplotypes. The complement of equine MHC class II DQ and DR genes appears to be
      well conserved between haplotypes, in contrast to the recently described
      variation in class I gene loci between equine MHC haplotypes. The identification
      of allelic series of equine MHC class II loci will aid comparative studies of
      mammalian MHC conservation and evolution and may also help to interpret
      associations between the equine MHC class II region and diseases of the horse.

PMID- 27889801
TI  - Production and purification of an untagged recombinant pneumococcal surface
      protein A (PspA4Pro) with high-purity and low endotoxin content.
AB  - Streptococcus pneumoniae is the main cause of pneumonia, meningitis, and other
      conditions that kill thousands of children every year worldwide. The replacement
      of pneumococcal serotypes among the vaccinated population has evidenced the need
      for new vaccines with broader coverage and driven the research for protein-based
      vaccines. Pneumococcal surface protein A (PspA) protects S. pneumoniae from the
      bactericidal effect of human apolactoferrin and prevents complement deposition.
      Several studies indicate that PspA is a very promising target for novel vaccine
      formulations. Here we describe a production and purification process for an
      untagged recombinant fragment of PspA from clade 4 (PspA4Pro), which has been
      shown to be cross-reactive with several PspA variants. PspA4Pro was obtained
      using lactose as inducer in Phytone auto-induction batch or glycerol limited fed
      batch in 5-L bioreactor. The purification process includes two novel steps: (i)
      clarification using a cationic detergent to precipitate contaminant proteins,
      nucleic acids, and other negatively charged molecules as the lipopolysaccharide,
      which is the major endotoxin; and (ii) cryoprecipitation that eliminates
      aggregates and contaminants, which precipitate at -20  degrees C and pH 4.0,
      leaving PspA4Pro in the supernatant. The final process consisted of cell rupture
      in a continuous high-pressure homogenizer, clarification, anion exchange
      chromatography, cryoprecipitation, and cation exchange chromatography. This
      process avoided costly tag removal steps and recovered 35.3 +/- 2.5% of PspA4Pro
      with 97.8 +/- 0.36% purity and reduced endotoxin concentration by >99.9%.
      Circular dichroism and lactoferrin binding assay showed that PspA4Pro secondary
      structure and biological activity were preserved after purification and remained
      stable in a wide range of temperatures and pH values.

PMID- 27889802
TI  - F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and
      histopathological validation of tumor lesions in prostate cancer patients.
AB  - PURPOSE: The prostate-specific membrane antigen (PSMA) targeted positron-emitting
      tomography (PET) tracer 68Ga-PSMA-11 shows great promise in the detection of
      prostate cancer. However, 68Ga has several shortcomings as a radiolabel including
      short half-life and non-ideal energies, and this has motivated consideration of
      18F-labelled analogs. 18F-PSMA-1007 was selected among several 18F-PSMA-ligand
      candidate compounds because it demonstrated high labelling yields, outstanding
      tumor uptake and fast, non-urinary background clearance. Here, we describe the
      properties of 18F-PSMA-1007 in human volunteers and patients. METHODS: Radiation
      dosimetry of 18F-PSMA-1007 was determined in three healthy volunteers who
      underwent whole-body PET-scans and concomitant blood and urine sampling.
      Following this, ten patients with high-risk prostate cancer underwent 18F-PSMA
      1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes
      were examined. Eight patients underwent prostatectomy with extended pelvic
      lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were
      correlated with final histopathology, including PSMA immunostaining. RESULTS:
      With an effective dose of approximately 4.4-5.5 mSv per 200-250 MBq examination,
      18F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other 18F
      labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, 18F-PSMA
      1007 has reduced urinary clearance enabling excellent assessment of the prostate.
      Similar to 18F-DCFPyL and with slightly slower clearance kinetics than PSMA-11,
      favorable tumor-to-background ratios are observed 2-3 h after injection. In eight
      patients, diagnostic findings were successfully validated by histopathology. 18F
      PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including
      nodes as small as 1 mm in diameter. CONCLUSION: 18F-PSMA-1007 performs at least
      comparably to 68Ga-PSMA-11, but its longer half-life combined with its superior
      energy characteristics and non-urinary excretion overcomes some practical
      limitations of 68Ga-labelled PSMA-targeted tracers.

PMID- 27889803
TI  - Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.
AB  - : Impaired diastolic filling is a main contributor to heart failure with
      preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no
      treatment. Both collagen and the giant sarcomeric protein titin determine
      diastolic function. Since titin's elastic properties can be adjusted
      physiologically, we evaluated titin-based stiffness as a therapeutic target. We
      adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout
      mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity
      does not only maintain cardiac filling in diastole but also ameliorates cardiac
      atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced
      RBM20 activity partially normalized gene expression related to muscle development
      and fatty acid metabolism. The adaptation of cardiac growth was related to
      hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that
      translate mechanical input into hypertrophy signals. We provide a novel link
      between cardiac isoform expression and trophic signaling via FHLs and suggest
      cardiac splicing as a therapeutic target in diastolic dysfunction. KEY MESSAGE:
      Increasing the length of titin isoforms improves ventricular filling in heart
      disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is
      a therapeutic target in diastolic dysfunction.

PMID- 27889804
TI  - Quest for Ancestors of Eukaryal Cells Based on Phylogenetic Analyses of Aminoacyl
      tRNA Synthetases.
AB  - The three-domain phylogenetic system of life has been challenged, particularly
      with regard to the position of Eukarya. The recent increase of known genome
      sequences has allowed phylogenetic analyses of all extant organisms using
      concatenated sequence alignment of universally conserved genes; these data
      supported the two-domain hypothesis, which place eukaryal species as ingroups of
      the Domain Archaea. However, the origin of Eukarya is complicated: the closest
      archaeal species to Eukarya differs in single-gene phylogenetic analyses
      depending on the genes. In this report, we performed molecular phylogenetic
      analyses of 23 aminoacyl-tRNA synthetases (ARS). Cytoplasmic ARSs in 12 trees
      showed a monophyletic Eukaryotic branch. One ARS originated from TACK
      superphylum. One ARS originated from Euryarchaeota and three originated from
      DPANN superphylum. Four ARSs originated from different bacterial species. The
      other 8 cytoplasmic ARSs were split into two or three groups in respective trees,
      which suggested that the cytoplasmic ARSs were replaced by secondary ARSs, and
      the original ARSs have been lost during evolution of Eukarya. In these trees, one
      original cytoplasmic ARS was derived from Euryarchaeota and three were derived
      from DPANN superphylum. Our results strongly support the two-domain hypothesis.
      We discovered that rampant-independent lateral gene transfers from several
      archaeal species of DPANN superphylum have contributed to the formation of
      Eukaryal cells. Based on our phylogenetic analyses, we proposed a model for the
      establishment of Eukarya.

PMID- 27889805
TI  - Air Pollution Study in the Republic of Moldova Using Moss Biomonitoring
      Technique.
AB  - Moss biomonitoring using the species Hypnum cupressiforme (Hedw.) and
      Pleurocarpous sp was applied to study air pollution in the Republic of Moldova. A
      total of 41 elements (Na, Mg, Al, Cl, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu,
      Zn, As, Se, Br, Rb, Sr, Zr, Cd, Sb, Cs, Ba, La, Ce, Nd, Sm, Eu, Gd, Tb, Tm, Yb,
      Hf, Ta, W, Pb, Th, and U) were determined by instrumental epithermal neutron
      activation analysis and atomic absorption spectrometry. Principal component
      analysis was used to identify and characterize different pollution sources.
      Geographical distribution maps were prepared to point out the regions most
      affected by air pollution and relate this to potential sources of contamination.
      Median values of the elements studied were compared with data from the European
      moss biomonitoring program. The cities of Chisinau and Balti were determined to
      experience particular environmental stress.

PMID- 27889806
TI  - A Comparative Assessment of Arsenic Risks and the Nutritional Benefits of Fish
      Consumption in Kuwait: Arsenic Versus Omega 3-Fatty Acids.
AB  - Inorganic and organic forms of arsenic (As), as well as omega-3 fatty acids were
      measured in 578 fish/seafood samples that belong to 15 species of commonly
      consumed seafood in Kuwait. Arsenic speciation data, with the toxicological
      profile of inorganic arsenic (iAs) and fish consumption rates were applied in a
      probabilistic risk assessment to estimate the risk from exposure to iAs. The
      nutritional benefits of omega-3-fatty acid levels in various species of fish were
      taken into consideration. Results showed that the mean daily intake of iAs
      through fish consumption among the Kuwaiti population was 0.058 ug/kg/day, and
      the 95th percentile was 0.15 ug/kg/day. Although the mean intake level did not
      exceed the incremental lifetime cancer risk (ILCR) at 1 * 10-4, the 95th
      percentile of iAs intake showed an ILCR of 2.7 * 10-4. Kuwaiti children (aged 6
      12 years) were found to have a higher mean intake of iAs at 0.10 ug/kg/day with
      68% of children in this category, exceeding the risk specific dose associated
      with an ILCR of 1 * 10-4. The fish species, hammor (grouper; Epinephelus
      coioides), is the top contributor to iAs intake, and tuna is the major source of
      omega 3-fatty acids for the Kuwaiti population.

PMID- 27889807
TI  - Vitamin D status in Bosnia and Herzegovina: the cross-sectional epidemiological
      analysis.
AB  - RATIONALE: Vitamin D deficiency/insufficiency/ is a worldwide epidemic in general
      population. The investigation of vitamin D concentrations in Bosnia and
      Herzegovina has never been conducted. MAIN RESULTS: A total of 82% from 2483
      examined patients have deficient/insufficient/ Vitamin D level. SIGNIFICANCE:
      These results encourage future studies to be focused on more specific details.
      INTRODUCTION: The goal of this paper was to evaluate the vitamin D concentrations
      in different cohort patients. Vitamin D deficiency is a global health problem. In
      Europe, hypovitaminosis D is even more prevalent. Vitamin D deficiency plays a
      significant role in a dozens of numerous disorders. METHODS: The cross-sectional
      epidemiological analysis was performed, and data were statistically analyzed. A
      total of 2483 screened individuals were examined for the serum 25(OH)D
      concentrations. The cutoff points that we used was <20 ng/mL. RESULTS: Among 2483
      examined patients for vitamin D level, females were in majority with 76% and
      males with 24% in total. Deficient vitamin D level was found in 60.6% of
      patients, and insufficient vitamin D level was detected in 21.4%. The highest
      rate of severe deficiency was found among elderly people (32.9%). In total, the
      decreased level of vitamin D concentration in Bosnia and Herzegovina is 82%.
      CONCLUSIONS: Vitamin D serum concentrations in Bosnia and Herzegovina are
      decreased in a majority of study population, and the results are within the
      average levels compared to other countries, particularly to findings in Central
      Europe. This analysis was based on patients, who have some health issues which
      may affect mobility, ability to go outside, food intake etc., so the level of
      25(OH)D seen in this paper may be an underestimate, and further research is
      required in the general and healthy population.

PMID- 27889809
TI  - Reversal of type 2 diabetes in youth who adhere to a very-low-energy diet: a
      pilot study.
AB  - AIMS/HYPOTHESIS: The aim of the study was to investigate whether a very-low
      energy diet (VLED) is a feasible and acceptable treatment option for type 2
      diabetes in children and adolescents, and whether adherence can lead to rapid
      weight loss, reversal of type 2 diabetes and reduced liver fat as seen in adult
      studies. METHODS: Eight participants with type 2 diabetes and obesity, aged 7-16
      years, non-medicated (n = 1) or treated with metformin (n = 7) and in some cases
      insulin (n = 3), followed a VLED (<3360 kJ/day) for 8 weeks, then transitioned to
      a hypocaloric diet (~6300 kJ/day) that they followed to 34 weeks. HbA1c, fasting
      glucose and 2 h post-glucose load plasma glucose (2hG) were determined from
      fasting blood and an OGTT. Liver fat concentration was quantified using proton
      magnetic resonance spectroscopy. Adherence was defined as >=5% weight loss during
      the 8 week VLED. RESULTS: Adherers (n = 5) and non-adherers (n = 3) had median
      weight loss of 7.5% and 0.5%, respectively, at 8 weeks. Overall, HbA1c (mean [SE]
      8.1% [0.7%] to 6.6% [0.5%]; p = 0.004) and 2hG (15.6 [1.6] mmol/l to 11.3 [1.0]
      mmol/l; p = 0.009) were significantly reduced at 8 weeks compared with baseline.
      Liver fat was also significantly reduced from baseline (14.7% [2.2%]) to 8 weeks
      (5.8% [1.7%]; p = 0.001). Only three out of eight participants met non-alcoholic
      fatty liver disease (NAFLD) criteria (>=5.5%) at 8 weeks, compared with eight out
      of eight at baseline. The three participants on insulin therapy at baseline were
      able to cease therapy during the 8 week VLED. At 34 weeks, adherers (n = 5)
      achieved 12.3% weight loss, none met NAFLD criteria and four did not meet
      American Diabetes Association criteria for type 2 diabetes.
      CONCLUSIONS/INTERPRETATION: A VLED appears to be a feasible treatment option for
      some youth with type 2 diabetes on metformin therapy. Youth who agree to
      participate and adhere to a VLED achieve rapid weight loss, dramatic reductions
      in liver fat and reversal of type 2 diabetes. This highlights the capacity of a
      VLED to be used as a first-line treatment option in newly diagnosed youth. A
      larger trial with a control group and longer follow-up will be required to
      encourage a change in standard treatment. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trial Registration Number (ACTRN) ACTRN12616000375459 (
      www.ANZCTR.org.au/ACTRN12616000375459.aspx ).

PMID- 27889808
TI  - Pharmacodynamic evaluation of Lys5, MeLeu9, Nle10-NKA(4-10) prokinetic effects on
      bladder and colon activity in acute spinal cord transected and spinally intact
      rats.
AB  - The purpose of this study was to determine feasibility of a novel therapeutic
      approach to drug-induced voiding after spinal cord injury (SCI) using a well
      characterized, peptide, neurokinin 2 receptor (NK2 receptor) agonist, Lys5,
      MeLeu9, Nle10-NKA(4-10) (LMN-NKA). Cystometry and colorectal pressure
      measurements were performed in urethane-anesthetized, intact, and acutely
      spinalized female rats. Bladder pressure and voiding were monitored in response
      to intravenous LMN-NKA given with the bladder filled to 70% capacity. LMN-NKA
      (0.1-300 MUg/kg) produced dose-dependent, rapid (<60 s), short-duration (<15 min)
      increases in bladder pressure. In intact rats, doses above 0.3-1 MUg/kg induced
      urine release (voiding efficiency of ~70% at >=1 MUg/kg). In spinalized rats,
      urine release required higher doses (>=10 MUg/kg) and was less efficient (30
      50%). LMN-NKA (0.1-100 MUg/kg) also produced dose-dependent increases in
      colorectal pressure. No tachyphylaxis was observed, and the responses were
      blocked by an NK2 receptor antagonist (GR159897, 1 mg/kg i.v.). No obvious
      cardiorespiratory effects were noted. These results suggest that rapid-onset,
      short-duration, drug-induced voiding is possible in acute spinal and intact rats
      with intravenous administration of an NK2 receptor agonist. Future challenges
      remain in regard to finding alternative routes of administration that produce
      clinically significant voiding, multiple times per day, in animal models of
      chronic SCI.

PMID- 27889810
TI  - Rhodamine bound maghemite as a long-term dual imaging nanoprobe of adipose tissue
      derived mesenchymal stromal cells.
AB  - In the last few years, magnetically labeled cells have been intensively explored,
      and non-invasive cell tracking and magnetic manipulation methods have been tested
      in preclinical studies focused on cell transplantation. For clinical
      applications, it is desirable to know the intracellular pathway of nanoparticles,
      which can predict their biocompatibility with cells and the long-term imaging
      properties of labeled cells. Here, we quantified labeling efficiency,
      localization, and fluorescence properties of Rhodamine derivatized
      superparamagnetic maghemite nanoparticles (SAMN-R) in mesenchymal stromal cells
      (MSC). We investigated the stability of SAMN-R in the intracellular space during
      a long culture (20 days). Analyses were based on advanced confocal microscopy
      accompanied by atomic absorption spectroscopy (AAS) and magnetic resonance
      imaging. SAMN-R displayed excellent cellular uptake (24 h of labeling), and no
      toxicity of SAMN-R labeling was found. 83% of SAMN-R nanoparticles were localized
      in lysosomes, only 4.8% were found in mitochondria, and no particles were
      localized in the nucleus. On the basis of the MSC fluorescence measurement every
      6 days, we also quantified the continual decrease of SAMN-R fluorescence in the
      average single MSC during 18 days. An additional set of analyses showed that the
      intracellular SAMN-R signal decrease was minimally caused by fluorophore
      degradation or nanoparticles extraction from the cells, main reason is a cell
      division. The fluorescence of SAMN-R nanoparticles within the cells was
      detectable minimally for 20 days. These observations indicate that SAMN-R
      nanoparticles have a potential for application in transplantation medicine.

PMID- 27889811
TI  - Bacterial Diversity Patterns Differ in Soils Developing in Sub-tropical and Cool
      Temperate Ecosystems.
AB  - Microbial diversity patterns have been surveyed in many different soils and
      ecosystems, but we are unaware of studies comparing similar soils developing from
      similar parent materials in contrasting climates. In 2008, developmental
      chronosequences with ages ranging from 105 to 500,000 years across Georgia (GA)
      and Michigan (MI) were studied to investigate how bacterial community composition
      and diversity change as a result of local environmental gradients that develop
      during pedogenesis. Geographic factors were studied between and within locations
      spanning two scales: (1) regionally between 0.1 and 50 and (2) ~1700 km apart.
      The diversity was surveyed using high-throughput pyrosequencing, and variance
      partitioning was used to describe the effects of spatial, environmental, and
      spatio-environmental factors on bacterial community composition. At the local
      scale, variation in bacterial communities was most closely related to
      environmental factors (rM = 0.59, p = 0.0001). There were differences in
      bacterial communities between the two locations, indicating spatial biogeography.
      Estimates of bacterial diversity were much greater in MI (numbers of OTU, ACE,
      and Chao1) and remained 2-3* greater in MI than GA after removing the effect of
      soil properties. The large differences in diversity between geographically
      separated bacterial communities in different climates need further investigation.
      It is not known if the rare members of the community, which contributed to
      greater bacterial diversity in GA relative to MI, play an important role in
      ecosystem function but has been hypothesized to play a role in ecosystem
      resiliency, resistance, and stability. Further research on the link between
      bacterial diversity and spatial variability related to climate needs further
      investigation.

PMID- 27889812
TI  - Research progress of hydroxychloroquine and autophagy inhibitors on cancer.
AB  - PURPOSE: Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect
      of chemotherapies and radiotherapy on various tumors identified in the current
      clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern
      worldwide. Thus, the potent autophagy inhibitors are urgently needed. METHODS: A
      systematic review was related to 'hydroxychloroquine' or 'chloroquine' with
      'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many
      cross-references involving HCQ, and these data have been incorporated into the
      following study. RESULTS: Many preclinical studies indicate that the combination
      of HCQ with chemotherapies or radiotherapies may enhance the effect of
      anticancer, providing base for launching cancer clinical trials involving HCQ.
      The new and more sensitive diagnostic techniques report a prevalence of HCQ
      retinopathy up to 7.5%. Lys05, SAR405, verteporfin, VATG-027, mefloquine and
      spautin-1 may be potent autophagy inhibitors. CONCLUSION: Additional mechanistic
      studies of HCQ in preclinical models are still required in order to answer these
      questions whether HCQ actually inhibits autophagy in non-selective tumors and
      whether the extent of inhibition would be sufficient to alter chemotherapy or
      radiotherapy sensitivity.

PMID- 27889813
TI  - Pediatric Radiology editorial board - acknowledgments and updates.

PMID- 27889814
TI  - An fMRI study of training voluntary smooth circular eye movements.
AB  - Despite a large number of recent studies, the promise of fMRI methods to produce
      valuable insights into motor skill learning has been restricted to sequence
      learning paradigms, or manual training paradigms where a relatively advanced
      capacity for sensory-motor integration and effector coordination already exists.
      We therefore obtained fMRIs from 16 healthy adults trained in a new paradigm that
      demanded voluntary smooth circular eye movements without a moving target. This
      aimed to monitor neural activation during two possible motor learning processes:
      (a) the smooth pursuit control system develops a new perceptual-motor
      relationship and successfully becomes involved in voluntary action in which it is
      not normally involved or (b) the saccadic system normally used for voluntary eye
      movement and which only exhibits linear action skill develops new dynamic
      coordinative control capable of smooth circular movement. Participants were able
      to improve within half an hour, typically demonstrating saccadic movement with
      progressively reduced amplitudes, which better approximated smooth circular
      movement. Activity in the inferior premotor cortex was significantly modulated
      and decreased during the progress of learning. In contrast, activations in dorsal
      premotor and parietal cortex along the intraparietal sulcus, the supplementary
      eye field and the anterior cerebellum did not change during training. Thus, the
      decrease of activity in inferior premotor cortex was critically related to the
      learning progress in visuospatial eye movement control.

PMID- 27889815
TI  - Modulating adaptation to emotional faces by spatial frequency filtering.
AB  - In four experiments, we investigated the presence and strength of perceptual
      aftereffects to emotional faces, using spatial frequency filtering to manipulate
      awareness of emotional content. We presented angry and happy faces as adapters
      and used a control condition without adaptation. Participants were subsequently
      requested to judge the friendliness level of a neutral target face. We confirmed
      the well-known aftereffect for unfiltered emotional faces in Experiment 1. In the
      experiment, friendliness judgments were greater for the angry than the happy or
      the control condition. In Experiment 2, in which the "hidden" emotional
      expression contained in the low spatial frequencies (LSF) was superimposed to the
      neutral expression presented in the rest of SF of the same image (emotional
      hybrid faces), the difference in friendliness judgments between angry and happy
      was significant, but none of the two conditions significantly differed from the
      control. In Experiment 3, faces were presented at LSF, confirmed a difference
      between the two emotions, but only the judgments of angry faces differed from the
      control condition. In Experiment 4, we extended the initial finding to stimuli
      presented at middle and high spatial frequencies (M-HSF). Finally, a comparison
      among all experiments revealed that the aftereffect was stronger with angry faces
      filtered at M-HSF than all of the other filtering conditions, whereas there were
      no differences for happy faces. We conclude that spatial frequency filtering
      influences aftereffects and that these effects are also related to emotional
      awareness. The results are discussed with reference to the dual route model of
      visual perception.

PMID- 27889816
TI  - Author reply - Letter to the Editor Re: Singh I et al: Growing skull fractures:
      guidelines for early diagnosis and surgical management.

PMID- 27889817
TI  - Paediatric spinal cord infarction-a review of the literature and two case
      reports.
AB  - Ischemic spinal cord infarction is rare in the paediatric population, and when it
      does occur, it is usually associated with traumatic injury. Other potential
      causes include congenital cardiovascular malformations, cerebellar herniation,
      thromboembolic disease and infection. Magnetic resonance imaging (MRI) findings
      can be subtle in the early evaluation of such patients. The outcome is variable
      and depends on the level and extent of the spinal cord infarct and subsequent
      rehabilitation. Here, we present two cases of ischemic spinal cord infarction in
      children.

PMID- 27889818
TI  - Somatosensory reflex seizures in a child with epilepsy related to novel SCN1A
      mutation.
AB  - INTRODUCTION: Mutations in SCN1A have been reported in patients with different
      types of epilepsy, including generalized epilepsy with febrile seizures plus,
      severe myoclonic epilepsy in infancy, malignant migrating partial seizures in
      infancy, and other infantile epileptic encephalopathies. CASE REPORT: We report a
      case of a 10-month-old girl presented with reflex epileptic seizures provoked by
      somatosensory stimuli with a novel de novo mutation of SCN1A gene. She was
      observed to have seizures with eye deviation, unresponsiveness provoked by
      somatosensory stimuli of the face. Video-electroencephalography (EEG) revealed
      generalized spike-and-wave patterns. She experienced one or two focal clonic
      seizures per month over the 6 months while taking valproate and carbamazepine. At
      22 months old, she was hospitalized with an episode of generalized tonic clonic
      febrile status epilepticus lasting for 45 min. Interictal sleep video-EEG showed
      sharp-and-slow wave discharges in the left occipital lobe with normal background
      activity. We found a de novo heterozygote mutation in SCN1A gene, c.1337A>C (p.
      Q422P). CONCLUSION: To our knowledge, this mutation has not been previously
      described in the SCN1A gene and this is the first report of epilepsy related to
      SCN1A mutation as a presenting with reflex epilepsy of somatosensory stimuli.
      This case report contributes to an expanding clinical spectrum of patients with
      SCN1A mutations.

PMID- 27889819
TI  - Pediatric traumatic brain injury: discussion about hyperosmolar therapy.

PMID- 27889820
TI  - Ruxolitinib in clinical practice for primary and secondary myelofibrosis: an
      analysis of safety and efficacy of Gruppo Laziale of Ph-negative MPN.
AB  - Ruxolitinib, a JAK1 and JAK2 inhibitor, has been tested and approved for the
      treatment of primary and secondary myelofibrosis (MF). Aim of our study is to
      report safety and efficacy of ruxolitinib in 98 patients affected by MF treated
      outside clinical trials and collected and treated consecutively by the Lazio
      Cooperative Group for Ph negative myeloproliferative diseases.There were 45 males
      and 53 females; median age was 61.8 years (range 35.3-88). Forty-five patients
      were diagnosed as primary MF and 53 as secondary MF. Seventy-seven patients
      (78.5%) experienced constitutional symptoms at baseline, and out of 94 patients
      tested, 66 (70%) were JAK2V617F mutated. Overall, 40 patients received
      hydroxyurea as firstline treatment, 30 patients received other chemotherapeutic
      approaches, whereas 28 were treated with ruxolitinib frontline. Median time from
      diagnosis to start of ruxolitinib in the whole cohort was 34.6 months. Fifty
      eight patients (59%) required a dose reduction during the first 3 months due to
      hematological toxicity in the majority of cases. At 48 weeks, 52% of patients
      obtained a clinical benefit: of them 7 patients (7%) had a CR, 10 (10%) a PR, 6
      patients (6%) a CI, and 28 patients (28.5%) a spleen response. Overall, 66% of
      patients had disappearance of baseline symptoms burden. After 1 year, of 72
      evaluable patients, 52% achieved and maintained a clinical benefit. Adverse
      events of special interest at any grade included anemia (39.7%), thrombocytopenia
      (25.5%), infections (16.3%, of which 10 were bronchopneumonia), fluid retention
      (3%), diarrhea (2%) and abdominal pain (2%). After a median follow-up of 16
      months from start of ruxolitinib, median daily dose decreased to 10 mg BID and 21
      patients (21%) discontinued the drug. The results of this retrospective
      multicentric analysis confirmed the efficacy of ruxolitinib outside clinical
      trials with more than half of treated patients achieving and maintaining a
      clinical benefit and most of them reporting relief from symptoms.

PMID- 27889821
TI  - Fundoplication with gastrostomy vs gastrostomy alone: a systematic review and
      meta-analysis of outcomes and complications.
AB  - PURPOSE: We compare the outcomes of fundoplication with gastrostomy vs
      gastrostomy alone and review the need for subsequent fundoplication after the
      initial gastrostomy alone. METHODS: We searched studies published from 1969 to
      2016 for comparative outcomes of concomitant fundoplication with gastrostomy
      (FGT) vs gastrostomy insertion alone (GT) in children. Gastrostomy methods
      included open, laparoscopic, and endoscopic procedures. Primary aims were minor
      and major complications. Secondary aims included post-operative reflux-related
      complications, fundoplication specific complications, and need for subsequent
      fundoplication after GT. RESULTS: We reviewed 447 studies; 6 observational
      studies were included for meta-analysis, encompassing 2730 children undergoing GT
      (n = 1745) or FGT (n = 985). FGT was associated with more minor complications
      [19.9 vs 11.4%, OR 2.02, 95% confidence interval (CI) 1.43-2.87, p <= 0.0001, I 2
      = 0%], minor complications requiring revision (6.8 vs 3.0%, OR 2.27, 95% CI 1.28
      4.05, p = 0.005, I 2 = 0%), and more overall complications (21.3 vs 12.0%, OR
      1.99, 95% CI 1.43-2.78, p < 0.0001, I 2 = 0%). Incidence of major complications
      (1.8 vs 2.0%, OR 1.39, 95% CI 0.62-3.11, p = 0.42, I 2 = 5%) and reflux-related
      complications (8.8 vs 10.3%, OR 0.75, 95% CI 0.35-1.68, p = 0.46, I 2 = 0%) in
      both groups was similar. Incidence of subsequent fundoplication in GT patients
      was 8.6% (mean). CONCLUSIONS: Gastrostomy alone is associated with fewer minor
      and overall complications. Concomitant fundoplication does not significantly
      reduce reflux-related complications. As few patients require fundoplication after
      gastrostomy, current evidence does not support concomitant fundoplication.

PMID- 27889822
TI  - Does the depth of mesorectal invasion have prognostic significance in patients
      with ypT3 lower rectal cancer treated with preoperative chemoradiotherapy?
AB  - PURPOSE: The prognostic significance of the depth of mesorectal invasion (DMI) in
      patients with ypT3 rectal cancer who undergo preoperative chemoradiotherapy (CRT)
      is unclear. The purpose of this study was to evaluate the prognostic significance
      of DMI in ypT3 rectal cancer. METHODS: A total of 168 (y)pT3 patients were
      evaluated, of whom 93 received preoperative CRT and 75 underwent surgery alone.
      Patients were subdivided into two groups according to the DMI (T3ab = DMI <=5 mm
      and T3cd = DMI >5 mm). Oncologic outcomes were compared between the T3ab and T3cd
      groups and the ypT3ab and ypT3cd groups. RESULTS: Relapse-free survival was
      significantly different between the pT3ab and pT3cd groups (74.1 vs 38.5%, P =
      0.0192) but not between the ypT3ab and ypT3cd groups (65.9 vs 61.5%, P = 0.513).
      Multivariate analysis showed that DMI was an independent predictor of recurrence
      in pT3 patients (hazard ratio [HR] = 2.980, 95% confidence interval [CI] 1.227
      7.025; P = 0.0169) and that ypN+ was an independent predictor of recurrence in
      ypT3 patients (HR = 3.487, 95% CI 1.570-8.827; P = 0.0016). CONCLUSIONS: DMI was
      not a significant predictive factor for recurrence in patients with ypT3 rectal
      cancer who underwent preoperative CRT, and ypN+ was the only independent
      predictive factor for recurrence.

PMID- 27889823
TI  - Goshajinkigan for reducing chemotherapy-induced peripheral neuropathy: protocol
      for a systematic review and meta-analysis.
AB  - PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is an issue for both
      cancer patients and specialists, and the number of cases of CIPN is growing with
      the increasing number of cancer patients worldwide. CIPN is often caused by
      common anticancer drugs such as taxanes and platinum analogs. These are key drugs
      for various cancers including colorectal and gastric cancers. However, there are
      currently no effective drugs to prevent CIPN. Goshajinkigan, a Japanese
      traditional herbal medicine (Kampo), is a promising drug which is used to treat
      diabetic neuropathy in Japan. This systematic review will assess the efficacy and
      safety of Goshajinkigan for reducing CIPN in cancer patients receiving
      chemotherapy. METHODS AND ANALYSIS: We will conduct a comprehensive search of
      relevant randomized controlled trials in Scopus, Ovid MEDLINE, Cochrane Central
      Register of Controlled Trials, and ICHUSHI. Two review authors will independently
      assess studies for inclusion and consult a third review author if necessary. The
      risk of bias of the included studies will be assessed according to the Cochrane
      risk of bias tool. We will investigate heterogeneity using forest plots and the
      chi-square test. When there are enough studies and any heterogeneity, we will use
      a random-effects model. Otherwise, we will use a fixed-effects model. ETHICS AND
      DISSEMINATION: This is a protocol for systematic review and meta-analysis and
      does not need ethics approval. We will disseminate the findings of this review
      through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:
      PROSPERO CRD42016045224.

PMID- 27889824
TI  - Erratum to: Counter-flow suggests transport of dantrolene and 5-OH dantrolene by
      the organic anion transporters 2 (OAT2) and 3 (OAT3).

PMID- 27889825
TI  - A critical review of complementary and alternative medicine use among people with
      arthritis: a focus upon prevalence, cost, user profiles, motivation, decision
      making, perceived benefits and communication.
AB  - A critical review of complementary and alternative medicine (CAM) use among
      people with arthritis was conducted focusing upon prevalence and profile of CAM
      users as well as their motivation, decision-making, perceived benefits and
      communication with healthcare providers. A comprehensive search of peer-reviewed
      literature published from 2008 to 2015 was undertaken via CINAHL, Medline and
      AMED databases. The initial search identified 4331 articles, of which 49 articles
      met selection criteria. The review shows a high prevalence of CAM use (often
      multiple types and concurrent to conventional medical care) among those with
      arthritis which is not restricted to any particular geographic or social-economic
      status. A large proportion of arthritis sufferers using CAM consider these
      medicines to be somewhat or very effective but almost half do not inform their
      healthcare provider about their CAM use. It is suggested that rheumatologists and
      others providing health care for patients with arthritis should be cognizant of
      the high prevalence of CAM use and the challenges associated with possible
      concurrent use of CAM and conventional medicine among their patients.

PMID- 27889826
TI  - Cardiovascular risk profiles in a hospital-based population of patients with
      psoriatic arthritis and ankylosing spondylitis: a cross-sectional study.
AB  - The objective of the study was to investigate the frequency of traditional risk
      factors for the cardiovascular (CV) disease, to calculate the Systematic COronary
      Risk Evaluation (SCORE) for CV-related mortality in Danish patients with
      psoriatic arthritis (PsA) and ankylosing spondylitis (AS), and to compare with
      results from patients with rheumatoid arthritis (RA) from the same settlement.
      All PsA and AS patients aged 18-85 years from one outpatient clinic were invited.
      A rheumatology nurse conducted 30-min screening consultation, preceded by a lipid
      and glucose profile. High SCORE risk led to recommendation of follow-up by
      general practitioners. Multiple and logistic regression analyses, adjusted for
      age and gender, were performed, to compare risk factors and risk SCOREs.
      Participants were 116 AS (29.3% female) and 170 PsA (54.7% female). AS had
      opposed PsA patients' lower 10-year risk SCOREs of CV mortality than RA patients:
      AS versus RA coefficient -0.47 (confidence interval (CI) 95%: -0.84 to -0.) and
      PsA versus RA -0.14, (-0.43-0.16). Women with PsA and AS had increased waistline
      compared to women with RA [PsA vs. RA 7.94 (4.51-11.38); AS versus RA 6.67 (1.17
      12.17)], and an increased prevalence of hypertension was seen in AS versus RA
      patients [1.87 (1.15-3.05)]. Traditional, modifiable CV risk factors were present
      in PsA and AS patients. AS but not PsA patients had an estimated lower 10-year
      risk of CV mortality than RA patients, according to the SCORE model adjusted for
      age and gender.

PMID- 27889827
TI  - The effect of routine training on the self-efficacy of informal caregivers of
      colorectal cancer patients.
AB  - PURPOSE: Little is known about the degree to which caregiver training as part of
      routine clinical care influences caregiver self-efficacy. The objective of this
      study was to examine the relationship between training during routine clinical
      cancer care and self-efficacy among caregivers of colorectal cancer patients.
      METHODS: Caregivers completed a self-administered questionnaire about their
      experiences with training for specific patient problems and about their task
      specific and general caregiving self-efficacy. Associations between training and
      self-efficacy were examined for each problem using multivariate logistic
      regression adjusted for caregiver age, race, care burden, education, perception
      of patient's health, and patient stage of disease. RESULTS: Four hundred
      seventeen caregivers completed the survey (70% response rate), of whom 374 (90%)
      were female and 284 (68%) were the patient's spouse/partner. Overall, 77 (38%)
      reported inadequate training for pain, 80 (38%) for bowel, 121 (48%) for fatigue,
      65 (26%) for medication administration, and 101 (40%) for other symptoms. The
      odds of having low self-efficacy were significantly higher among those with
      perceptions of inadequate training across the following cancer-related problems:
      pain 10.10 (3.36, 30.39), bowel 5.04 (1.98, 12.82), fatigue 8.45 (3.22, 22.15),
      managing medications 9.00 (3.30, 24.51), and other 3.87 (1.68, 8.93).
      CONCLUSIONS: Caregivers commonly report inadequate training in routine colorectal
      cancer care. Significant and consistent associations between training adequacy
      and self-efficacy were found. This study supports the value of training
      caregivers in common cancer symptoms. Further work on how and when to provide
      caregiver training to best impact self-efficacy is needed.

PMID- 27889828
TI  - Physicians' practice of discussing fertility preservation with cancer patients
      and the associated attitudes and barriers.
AB  - PURPOSE: The aim of this study is to describe physicians' clinical practice of
      discussing fertility issues with cancer patients and determine the factors
      associated with such discussion. METHODS: In this cross-sectional study, a
      nationwide Internet survey was conducted among physicians who provided daily
      medical care to cancer patients at hospitals or clinics. Participants answered a
      questionnaire assessing characteristics, discussion practices, attitudes, and
      barriers regarding fertility preservation. RESULTS: Among the 180 participants,
      42% discussed fertility issues with patients daily, and 30% had experience in
      referring patients to fertility preservation specialists. A multivariate logistic
      regression analysis showed that those who agreed or strongly agreed with the
      statements "physicians are responsible for discussing fertility preservation" (OR
      = 2.04, 95% CI 1.14-3.63, p < 0.05) and "patients who have an exceedingly
      aggressive disease and need immediate cancer treatment should not be told about
      fertility issues" (OR =1.84, 95% CI 1.09-3.10, p < 0.05) were nearly twice as
      likely to discuss fertility issues with patients. CONCLUSIONS: Compared to
      Western countries, fertility issues are less likely to be discussed in Japan. To
      increase opportunities for patients to discuss fertility issues, the ASCO
      guidelines should be widely understood. Additionally, these results suggest that
      physicians who are more likely to discuss fertility issues might feel more
      conflicted about whether they in fact should discuss such issues with patients
      with poor prognosis or insufficient time for cancer treatment.

PMID- 27889829
TI  - Sexual function changes during pregnancy.
AB  - INTRODUCTION AND HYPOTHESIS: We describe changes in sexual activity and function
      among pregnant nulliparous women. METHODS: This secondary analysis evaluated
      sexual activity and function with the Female Sexual Function Index (FSFI) at
      baseline in the first (T1), second (T2) and early third (T3) trimester.
      Evaluation was repeated in T3 after 36 completed weeks of gestation. Data were
      assigned to the trimester in which they were collected and compared across
      trimesters. FSFI items were dichotomized into favorable and unfavorable
      responses. ANOVA and logistic regression models were used to compare values
      across trimesters, taking into account repeated measurements. Pair-wise
      comparisons of trimesters were done when there were significant overall
      differences. Significance was set at p < 0.05. We adjusted for baseline
      differences. RESULTS: Of 627 women, four did not give sexual function data.
      Baseline data were collected in 124 women in T1, 403 in T2, and 96 in early T3.
      Of these 623 women, 496 (80 %) gave data again in T3. The participants' mean age
      was 24.2 +/- 5.1 years and 44.5 % were Hispanic. Rates of sexual activity (T1 94
      %, T2 90 %, T3 77 %; p < 0.001) and mean FSFI scores decreased as pregnancy
      progressed (T1 26.5 +/- 7.7, T2 25.6 +/- 9.0, T3 21.5 +/- 10.3; T1/T2 vs. T3, p <
      0.001). Using the FSFI cut-off score for sexual dysfunction of 26.55, women in T3
      were more likely to report dysfunction than women in T2 (57 % vs. 37 %, p <
      0.001). For specific FSFI questions, the proportions of women reporting favorable
      responses did not change between T1 and T2 (all p > 0.05) and the proportions of
      women with a favorable response decreased for all questions between T2 and T3.
      CONCLUSIONS: As pregnancy progresses, women report poorer sexual function.

PMID- 27889830
TI  - Urinary retention in female OAB after intravesical Botox injection: who is really
      at risk?
AB  - INTRODUCTION AND HYPOTHESIS: Intravesical onabotulinumtoxinA (Botox) injections
      are effective for the treatment of idiopathic overactive bladder (OAB) symptoms.
      The aim of our study was to assess the predisposing factors for urinary retention
      in women with OAB after intravesical Botox injection. METHODS: All participants
      were women of European descent with idiopathic OAB. OnabotulinumtoxinA (100 U)
      was administered in 20 intra-detrusor injections. Analysis was performed based on
      the results of safety assessments made during follow-up (FU) visits on weeks 2, 4
      and 12, in 208 women who were treated with Botox injections for refractory OAB
      and who completed all FU visits. RESULTS: Women who required clean intermittent
      self-catheterisation (CISC) and those with post-void residual (PVR) greater than
      200 ml were older in comparison with patients with PVR between 50 and 200 ml.
      Patients who required CISC were also characterised by higher parity and
      particularly by a higher number of vaginal deliveries. Other factors such as body
      mass index or comorbidities did not significantly influence PVR and the risk of
      CISC. CONCLUSIONS: Elderly and/or multiparous women are at increased risk of
      urinary retention after intravesical 100-U Botox injections. The risk of new
      onset urine retention in our study has completely disappeared 2 weeks after Botox
      injections. Based on our results of the way in which the PVRs have changed over
      time, we can conclude that OAB patients should be optimally assessed during the
      first 2 weeks after Botox injections.

PMID- 27889831
TI  - An ecophysiological background for biogeographic patterns of two island lizards?
AB  - Distributions of sedentary ectotherms are dependent on temperature and humidity
      due to their low homeostatic and dispersal abilities. Lizards are strongly
      conditioned by temperature, but hydric environment may be also important, at
      least in arid environments. Biotic interactions may also play a role in range
      patterns, but they are of minor importance in islands where native species
      monopolize well-delimited niche spaces. On the arid island of Sao Vicente (Cabo
      Verde), two endemic lizards display different spatial patterns. While the gecko
      Tarentola substituta is widely distributed across the island, the skink Chioninia
      stangeri is restricted to the NE, which is cooler, more humid, and vegetated. We
      hypothesized that this is due to differences in the fundamental niche,
      specifically in ecophysiology. We predict that C. stangeri should select for
      lower temperatures and lose more water by evaporation than T. substituta. We
      submitted adults of each species to standard experiments to assess preferred body
      temperatures (Tp) and evaporative water loss (EWL) rates, and examined the
      variation between species and through time using repeated-measures AN(C)OVAs.
      Results only partially supported our expectations. Contrary to the prediction,
      skinks attained higher Tp than geckos but in the long term showed a trend for
      higher EWL as predicted. Thus, while ecophysiology certainly contributes to
      functional interpretation of species distributions, it needs to be combined with
      other evidence such as habitat use and evolutionary history. These findings will
      be useful to perform mechanistic models to better understand the impact of
      climate change and habitat disturbance on these endemic species.

PMID- 27889832
TI  - Effects of cytochrome P450 (CYP3A4 and CYP2C19) inhibition and induction on the
      exposure of selumetinib, a MEK1/2 inhibitor, in healthy subjects: results from
      two clinical trials.
AB  - PURPOSE: Two phase I, open-label trials in healthy subjects assessed whether co
      administration with CYP3A4/CYP2C19 inhibitors, itraconazole/fluconazole (study
      A), or CYP3A4 inducer, rifampicin (study B), affects the exposure,
      safety/tolerability and pharmacokinetics of selumetinib and its metabolite N
      desmethyl selumetinib. METHODS: In study A (n = 26), subjects received a single
      dose of selumetinib 25 mg and, after 4 days of washout, were randomized to
      treatment 1 (itraconazole 200 mg twice daily on days 1-11) or treatment 2
      (fluconazole 400 mg on day 1 then 200 mg/day on days 2-11) plus co-administration
      of single-dose selumetinib 25 mg on day 8 (selumetinib staggered 4 h after
      itraconazole/fluconazole dose); Twenty-one days after discharge/washout, subjects
      received the alternate treatment. In study B (n = 22), subjects received a single
      dose of selumetinib 75 mg (day 1) then rifampicin 600 mg/day (days 4-14) plus a
      single dose of selumetinib 75 mg on day 12. Pharmacokinetic analysis and safety
      assessments were performed. RESULTS: Selumetinib co-administered with
      itraconazole, fluconazole (selumetinib staggered 4 h after
      itraconazole/fluconazole dose), or rifampicin was well tolerated. Selumetinib
      exposure was higher when co-administered with itraconazole or fluconazole (area
      under the plasma concentration-time curve (AUC) increased by 49 and 53%,
      respectively; maximum plasma concentration (C max) increased by 19 and 26%,
      respectively) but lower when co-dosed with rifampicin (AUC and C max decreased by
      51 and 26%, respectively) versus selumetinib dosed alone. Co-administration with
      itraconazole or rifampicin decreased N-desmethyl selumetinib AUC(0-t) (11 and
      55%, respectively), and C max (25 and 18%, respectively), with fluconazole, AUC(0
      t) increased by 40%, but there was no effect on C max. CONCLUSIONS: Co
      administration of CYP3A4/CYP2C19 inhibitors will likely increase exposure to
      selumetinib, while CYP3A4 inducers will likely reduce its exposure.

PMID- 27889833
TI  - Factors associated with expression of extrapyramidal symptoms in users of
      atypical antipsychotics.
AB  - PURPOSE: The aim of this study was to investigate factors associated with the
      occurrence of extrapyramidal symptoms (EPS) in users of second-generation
      antipsychotics (SGA). METHODS: Observational cross-sectional study based on a
      random sample of subjects from three outpatient clinics. Inclusion criteria were
      age between 18 and 65 years, of both genders, with a diagnosis of schizophrenia
      and under the use of a single SGA agent. Subjects who had received i.m. long
      acting antipsychotics in the past were excluded. The families of eligible
      patients were contacted by phone and, if willing to participate in the study, a
      household visit was scheduled. Informed consent was obtained from all study
      subjects and their next of kin. The risk of EPS associated with sociodemographic,
      clinical features and medications used was analyzed by logistic regression.
      RESULTS: The study population consisted of 213 subjects. EPS were observed in
      38.0% of subjects. The more commonly used SGA were olanzapine (76, 35.7%),
      risperidone (74, 34.3%), quetiapine (26, 12.2%), and ziprasidone (23, 10.8%).
      Among the drugs used as adjunctive therapy for schizophrenia, benzodiazepines
      were the most prevalent (31.5%), followed by carbamazepine (24.4%) and
      antidepressants (20.2%). Multivariate analysis showed that the risk of EPS was
      associated with the use of carbamazepine (odds ratio 3.677, 95% CI 1.627-8.310).
      We found no evidence that the type of SGA modified the risk of EPS. CONCLUSION:
      The occurrence of EPS in SGA users is a common finding, with no difference of
      antipsychotics studied in relation to the risk of extrapyramidal manifestations.
      The adjunctive use of carbamazepine may predispose the user of SGA to the
      occurrence of EPS.

PMID- 27889834
TI  - Antiepileptic drug use in Italian children over a decade.
AB  - PURPOSE: The aim of the study was to evaluate prescription profiles of
      antiepileptic drugs (AEDs) and to assess hospitalizations and specialist visits
      in pediatric patients with epilepsy. METHODS: The data sources were
      administrative health databases of Italy's Lombardy Region, which collect
      prescriptions for drugs, diagnostic tests, specialist visits, and hospital
      discharge forms. All patients aged 0-16 years with at least seven AED (group N03A
      of the International Anatomical Therapeutic Chemical Classification)
      prescriptions over two consecutive years between 2003 and 2010 were identified
      and classified as prevalent or incident cases (no prescriptions in two previous
      years). The first prescription to incident cases was analyzed. For each incident
      case, drug prescriptions, specialist visits, diagnostic tests, and
      hospitalizations in the 24 months following the first (index) prescription were
      monitored. RESULTS: A total of 6527 incident cases (5.4/10,000 person-years, 95%
      CI 5.4-5.5) were identified. Valproic acid and carbamazepine were the most
      prescribed drugs (65.9 and 15.0%, respectively). The use of newer AEDs increased
      over time. In the 24-month observation period, 74% of incident cases continued
      the treatment with the index AED. The percentage of cases who changed therapy was
      higher in preschoolers (34%) and decreased with age. In all, 21% of incident
      cases were hospitalized for epilepsy and 86% had a specialist visit in the 24
      months after the first AED prescription. CONCLUSIONS: In conclusion, older AEDs,
      particularly valproic acid, remained the first therapeutic approach to pediatric
      epilepsy in Italy. For three quarters of cases, the initial AED treatment was
      likely effective and well tolerated.

PMID- 27889835
TI  - Valproic acid reduces hair loss and improves survival in patients receiving
      temozolomide-based radiation therapy for high-grade glioma.
AB  - PURPOSE: Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also
      used to manage seizures in glioblastoma patients. HDAC inhibitors can protect
      normal cells and tissues from the deleterious effects of radiotherapy, and VPA is
      reported to improve the survival of glioblastoma patients receiving
      chemoradiation therapy. VPA also promotes hair growth, and thus has the potential
      to reduce the radiotherapy side effect of hair loss while improving the survival
      of patients with glioblastoma. The purpose of this study was to determine whether
      VPA use during radiotherapy for high-grade glioma is associated with decreased
      side effects of radiotherapy and an improvement in overall survival (OS) and
      progression-free survival (PFS). METHODS: Medical records of 112 patients with
      high-grade glioma were retrospectively reviewed. We grouped patients by VPA use
      or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. RESULTS:
      The radiation dose and fractionation at the onset of hair loss were 4 Gy and two
      fractions higher, respectively, in the VPA group compared with the VPA non-use
      group (P < 0.01). Median OS was 42.2 and 20.3 months in the VPA use and non-use
      groups, respectively (P < 0.01; hazard ratio [HR], 0.36; 95% confidence interval
      [CI], 0.18-0.74). Median PFS was 22.7 and 11.0 months in the VPA use and non-use
      groups, respectively (P = 0.099; HR, 0.62; 95% CI, 0.36-1.09). CONCLUSIONS: VPA
      use during radiotherapy for glioma is associated with delayed hair loss and
      improvement in survival. Hair loss prevention benefits patients suffering from
      the deleterious effects of radiation.

PMID- 27889836
TI  - Clinical validation of synthetic brain MRI in children: initial experience.
AB  - INTRODUCTION: The purpose of this study was to determine the diagnostic accuracy
      of synthetic MR sequences generated through post-acquisition processing of a
      single sequence measuring inherent R1, R2, and PD tissue properties compared with
      sequences acquired conventionally as part of a routine clinical pediatric brain
      MR exam. METHODS: Thirty-two patients underwent routine clinical brain MRI with
      conventional and synthetic sequences acquired (22 abnormal). Synthetic axial T1,
      T2, and T2 fluid attenuation inversion recovery or proton density-weighted
      sequences were made to match the comparable clinical sequences. Two exams for
      each patient were de-identified. Four blinded reviewers reviewed eight patients
      and were asked to generate clinical reports on each exam (synthetic or
      conventional) at two different time points separated by a mean of 33 days. Exams
      were rated for overall and specific finding agreement (synthetic/conventional and
      compared to gold standard consensus review by two senior reviewers with knowledge
      of clinical report), quality, and diagnostic confidence. RESULTS: Overall
      agreement between conventional and synthetic exams was 97%. Agreement with
      consensus readings was 84% (conventional) and 81% (synthetic), p = 0.61. There
      were no significant differences in sensitivity, specificity, or accuracy for
      specific imaging findings involving the ventricles, CSF, brain parenchyma, or
      vasculature between synthetic or conventional exams (p > 0.05). No significant
      difference in exam quality, diagnostic confidence, or noise/artifacts was noted
      comparing studies with synthetic or conventional sequences. CONCLUSIONS:
      Diagnostic accuracy and quality of synthetically generated sequences are
      comparable to conventionally acquired sequences as part of a standard pediatric
      brain exam. Further confirmation in a larger study is warranted.

PMID- 27889837
TI  - Exercise training effects on memory and hippocampal viscoelasticity in multiple
      sclerosis: a novel application of magnetic resonance elastography.
AB  - INTRODUCTION: Cognitive impairment is common and debilitating among persons with
      multiple sclerosis (MS) and might be managed with exercise training. However, the
      effects of exercise training on viscoelastic brain properties in this population
      are unknown. The present pilot study adopted a single-blind randomized controlled
      trial (RCT) design and is the first to examine the effect of an aerobic exercise
      training intervention on learning and memory and hippocampal viscoelasticity
      using magnetic resonance elastography (MRE) in persons with MS. METHODS: Eight
      fully ambulatory females with MS were randomly assigned into exercise training
      intervention or waitlist control conditions. The intervention condition involved
      12 weeks of supervised, progressive treadmill walking exercise training. All
      participants underwent measures of learning and memory (i.e., California Verbal
      Learning Test-II; CVLT-II) and further underwent MRE scans for measurement of
      shear stiffness (MU) and damping ratio (xi) of the hippocampus before and after
      the 12-week period. RESULTS: Overall, there were small-to-moderate intervention
      effects on CVLT-II performance (d = 0.34) and large intervention effects on
      hippocampal MU (d = 0.94) and hippocampal xi (d = -1.20). Change in CVLT-II
      scores was strongly associated with change in MU (r = 0.93, p < 0.01) and xi (r =
      -.96, p < 0.01) of the hippocampus. CONCLUSION: This small pilot RCT provides
      exciting proof-of-concept data supporting progressive treadmill walking exercise
      training for potentially improving learning and memory and underlying hippocampal
      viscoelastic properties in persons with MS. This is important given the high
      prevalence and burden of MS-related memory impairment.

PMID- 27889838
TI  - Changes of brain metabolite concentrations during maturation in different brain
      regions measured by chemical shift imaging.
AB  - INTRODUCTION: We examined the effect of maturation on the regional distribution
      of brain metabolite concentrations using multivoxel chemical shift imaging.
      METHODS: From our pool of pediatric MRI examinations, we retrospectively selected
      patients showing a normal cerebral MRI scan or no pathologic signal abnormalities
      at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate
      global neurological development, except for focal neurological deficits. Seventy
      one patients (4.5 months-20 years) were identified. Using LC Model, spectra were
      evaluated from voxels in the white matter, caudate head, and corpus callosum.
      RESULTS: The concentration of total N-acetylaspartate increased in all regions
      during infancy and childhood except in the right caudate head where it remained
      constant. The concentration of total creatine decreased in the caudate nucleus
      and splenium and minimally in the frontal white matter and genu. It remained
      largely constant in the parietal white matter. The concentration of choline
      containing compounds had the tendency to decrease in all regions except in the
      parietal white matter where it remained constant. The concentration of
      myoinositol decreased slightly in the splenium and right frontal white matter,
      remained constant on the left side and in the caudate nucleus, and rose slightly
      in the parietal white matter and genu. CONCLUSION: CSI determined metabolite
      concentrations in multiple cerebral regions during routine MRI. The obtained data
      will be helpful in future pediatric CSI measurements deciding whether the ratios
      of the main metabolites are within the range of normal values or have to be
      considered as probably pathologic.

PMID- 27889839
TI  - What is the fate of the neck after a collum femoris preserving prosthesis? a
      nineteen years single center experience.
AB  - PURPOSE: The aim of our study is to evaluate long-term outcomes from a cohort of
      patients treated with collum femoris preserving (CFP) stem correlating neck
      resorption with comorbidities, clinical outcomes, and complications. METHODS: One
      hundred seventy-six patients (194 hips) were retrospectively reviewed with a
      minimum follow-up (f.u.) of ten years. Demographic and surgical data were
      collected. Clinical and radiological evaluation was performed at the last follow
      up. We calculated a neck resorption ratio (NRR) for each patient. Main
      complications were recorded. A p-value of <0.05 was considered significant.
      RESULTS: The mean Harris hip score (HHS) was 89.1 +/- 5.7. The mean visual
      analogue scale (VAS) and Oxford hip score (OHS) values were 1.1 +/- 1 and 41.3 +/
      5.1, respectively. The mean leg length discrepancy was 1.5 mm +/- 1.9. The mean
      NRR was 0.35. We observed six cases of aseptic loosening, two cases of infection,
      one implant revision for recurrent dislocation, and one stem revision after
      periprosthetic femoral fracture. The overall survival rate of the stem was 94.8%.
      Statistically significant associations were found between NRR and steroid
      therapy/stem malposition. Correlation between aseptic loosening and NRR was also
      statistically significant. Correlations between NRR and HHS/OHS were -0.34 and 
      0.28 respectively. Odds ratio for aseptic loosening were: 4.6 if NRR > 0.25; 16.9
      if > 0.50 and 24.1 if > 0.75. CONCLUSION: CFP hip stem provided excellent long
      term outcomes. NRR is correlated to steroid therapy and stem malposition. The
      risk of stem aseptic loosening rises according to NRR increase. Patients with an
      NRR > 0.5, especially if under steroid therapy or with stem malposition, should
      be strictly monitored.

PMID- 27889840
TI  - Five to thirteen year results of a cemented dual mobility socket to treat
      recurrent dislocation.
AB  - PURPOSE: Dual mobility (DM) socket has been associated with a low rate of
      dislocation following both primary and revision total hip arthroplasty (THA).
      However, little is known about the long-term efficiency of DM in the treatment of
      THA instability. The purpose of this retrospective study was to evaluate the
      outcome of a cemented DM socket to treat recurrent dislocation after a minimum of
      five year follow-up. METHODS: The series included 51 patients with a mean age of
      71.3 +/- 11.5 (range, 41-98) years presenting with recurrent dislocation (mean
      3.3). A single DM socket design was used consisting of a stainless steel outer
      shell with grooves with a highly polished inner surface articulating with a
      mobile polyethylene component. The femoral head was captured in the polyethylene
      component using a snap-fit type mechanism, the latter acting as a large
      unconstrained head inside the metal cup. RESULTS: At the minimum five year follow
      up evaluation, 18 of the 51 patients deceased at a mean of 4.8 +/- 2.3 years,
      three were lost to follow-up at a mean of 1.4 years, seven had been revised at a
      mean of 4.7 +/- 3.1 years (range, 1.5-9.1), and the remaining 23 were still alive
      and did not have revision at a mean of 8.2 +/- 2.4 years (range, 5-13 years). Of
      the seven revision, three were performed for further episodes of dislocation (at
      the large bearing for one patient and intra-prosthetic for two patients) after a
      mean 5.9 +/- 2.9 years (range, 2.7-9.1), whereas two were performed for late
      sepsis and two for aseptic loosening of the acetabular component. Radiographic
      analysis did not reveal any further loosening on the acetabular side. The
      survival rate of the cup at ten years, using re-dislocation as the end-point, was
      86.1 +/- 8.4% (95% confidence interval, 69.7-100%). The survival rate of the cup
      at ten years, using revision for any reason as the end-point, was 75.2 +/- 9.3%
      (95% confidence interval, 56.9-93.5%). CONCLUSION: A cemented dual mobility cup
      was able to restore hip stability in 94% of patients presenting with recurrent
      dislocating hips up to 13-year follow-up with none of the complications
      associated with constrained devices, as mechanical failure occurred in only 3.9%
      of the patients of this series. The overall reduced survival using revision for
      any reason as the end-point at ten years was related to this specific patients
      population that had various co-morbidities.

PMID- 27889841
TI  - The function of activatable cell-penetrating peptides in human intrahepatic bile
      duct epithelial cells.
AB  - This study aimed to investigate the function of Activatable Cell-Penetrating
      Peptides (ACPP) in detecting the changes of human intrahepatic bile duct
      epithelial cell(hIBDEC). ACPP, which target matrix metalloproteinases, were
      constructed. All were labeled with FITC and Gd-DTPA at the N-terminal.
      Fluorescence microscopy was used to observe the fluorescence intensity inside
      hIBDEC after stimulating with different concentrations of LPS and incubating with
      different concentrations of ACPP to determine the optimal concentration range for
      LPS stimulation and the optimal concentration for FITC-ACPP effect. Flow
      cytometry and magnetic resonance imaging were used to detect fluorescence signal
      intensity and nuclear magnetic resonance signal intensity, respectively, after
      stimulating with different concentrations of LPS. LPS stimulation time and ACPP
      incubation time were also evaluated, and variance analysis was conducted to
      analyze intracellular signal change characteristics for every group. Activatable
      Cell-Penetrating Peptides (ACPP), which were marked with FITC and Gd-DTPA had
      target-penetrating activity. The intracellular signal intensity gradually
      increased with the increase in LPS stimulation time and ACPP incubation time
      within a certain range; however, it did not increase with the increase of LPS
      concentration. ACPP can be used for imaging hIBDEC with epithelial-mesenchymal
      transition.

PMID- 27889842
TI  - Early differential diagnosis of the severity of acute pancreatitis.
AB  - There is a great need for early verification of the severity of acute
      pancreatitis (AP). The early stage of pathogenesis of AP is characterized by
      endothelial dysfunction which could be determined by wavelet analysis of skin
      temperature (WAST) technique. The aim is to investigate whether the dysregulation
      of microvascular tone caused by endothelial dysfunction and detected by WAST can
      be a significant indicator in early differential diagnosis of AP severity. The
      WAST performed in the frequency range of 0.0095-0.02 Hz during the contralateral
      cold test. Forty nine patients with AP aged 19-65 participated in this study. The
      control group included 12 healthy volunteers aged 20-65. Dysregulation of
      vascular tone during the contralateral cold test was observed in all patients
      with AP. The basal amplitudes of skin temperature oscillations in patients with
      AP were much lower than in healthy volunteers and progressively decreased as the
      disease severity increased. In patients with mild and moderate AP only the
      vasodilator component is destroyed, but vasoconstriction still operates. In
      patients with severe AP both mechanisms of endothelial vascular tone regulation
      are destroyed. Patients with AP have abnormal microvascular reactions related to
      the endothelial mechanism of vascular tone regulation. Based on the initial
      values of amplitudes and the indices of vasoconstriction and postcold
      vasodilatation, the WAST method makes it possible to evaluate two related but
      different characteristics of the endothelial dysfunction in patients with AP on
      admission which can be a significant indicator in early differential diagnosis of
      AP severity.

PMID- 27889844
TI  - Long-term use of the wearable cardioverter-defibrillator: prolonging life or
      prolonging indecision?

PMID- 27889843
TI  - A randomized comparison of the Ambu AuraGain versus the LMA supreme in patients
      undergoing gynaecologic laparoscopic surgery.
AB  - Second generation supraglottic airway devices providing high seal airway
      pressures are suitable for patients undergoing gynecologic laparoscopy. We
      compared the seal pressure achieved by the new Ambu AuraGainTM versus LMA
      SupremeTM following pneumoperitoneum in the Trendelenburg position. Sixty female
      patients were randomly allocated to ventilation with either the AuraGain or the
      Supreme. A target-controlled system was used to administer total intravenous
      anesthesia. Intracuff pressure was maintained below 60 cm H2O. The following
      parameters were registered: Time, number of attempts and manoeuvres required for
      insertion; seal pressure and peak inspiratory pressure at four time points; ease
      of gastric tube insertion, flexible scope view, complications and postoperative
      morbidity. Both devices were quick and easily inserted, although the Supreme
      required less rotation manoeuvres (16 in AuraGain vs. 6 in LMA Supreme; p =
      0.01). The AuraGain achieved higher seal pressures (34 +/- 5 in AuraGain vs. 29
      +/- 5 in LMA Supreme; p = 0.0002). Following pneumoperitoneum in head-down
      position, peak airway pressure increased 9 +/- 3 cm H2O in both groups, exceeding
      seal pressure in 3 patients in the Supreme group (p = 0.06). The vocal cords were
      seen through all AuraGain and 90% of the Supreme devices; epiglottis was often
      visible inside the tube (68%). No differences were found in the incidence of
      traces of blood on the mask or postoperative symptoms. Both devices allowed
      effective ventilation in patients undergoing gynaecologic laparoscopic surgery
      with a low rate of complications. The Ambu AuraGain provided higher seal
      pressures and a clear view of glottic inlet in all patients offering the
      possibility to guide direct tracheal intubation if required.

PMID- 27889845
TI  - Randomized trial comparing self gripping semi re-absorbable mesh (PROGRIP) with
      polypropylene mesh in open inguinal hernioplasty: the 6 years result.
AB  - OBJECTIVES: The use of absorbable polylactic acid hook self-gripping
      polypropylene mesh in open inguinal hernia may potentially reduce operative time
      and enhance patient recovery. The objective of this randomized trial is to
      compare the outcomes following self-gripping mesh repair to polypropylene mesh
      secured with sutures in open inguinal hernioplasty. METHOD: Eligible patients
      aged 18-80 years old, who had primary unilateral uncomplicated inguinal hernia,
      were randomized into either Polypropylene (PL) group or PROGRIP (PG) group just
      before the placement of mesh intra-operatively by computer generated code. The
      primary outcome was the time from mesh placement to end of operation, whereas
      secondary outcomes included the total operative time, amount of analgesic used,
      length of post-operative stay, seroma formation, chronic discomfort, chronic pain
      score and recurrence. The study has been registered in
      http://www.clinicaltrial.gov carrying an ID of NCT00960011. Patients were
      followed-up in outpatient clinic for up to 6 years after operation. RESULTS: From
      March 2009 to April 2016, 45 patients were included. The mean age of PG group (n
      = 22) was 62.0 +/- 15.7 years old while that of the PL group was 62.6 +/- 4.9
      years old (n = 23). There was no significant difference regarding the smoking
      habit, drinking habit, comorbidities, previous hernia operation and Nyhus type of
      hernia between the two groups. The size of defects, the time of groin dissection
      and the size of incision were similar. In the PG group, there was significant
      reduction in the time for mesh placement (11.8 +/- 3.1 vs. 21.0 +/- 6.2 min, p <
      0.001) and total operative time (39.2 +/- 9.8 vs. 47.7 +/- 8.0 min, p = 0.003).
      There was one recurrence in PL group and nil in PG group. Although there was a
      significant difference in paresthesia between 2 groups after operation, the
      difference disappears with time and comparable from post-operative 1 year
      onwards. There was no difference in chronic pain, chronic discomfort, affect
      daily activities, palpable mesh demonstrated throughout the whole study period
      till 6 years after operation. CONCLUSIONS: The use of polylactic acid self
      gripping mesh in open inguinal hernia repair effectively reduces the operating
      time with comparable long-term surgical outcome with traditional polypropylene
      mesh.

PMID- 27889846
TI  - Gastrointestinal Bleeding During Index Hospitalization for Mechanical Circulatory
      Support Devices Implantation: Is the Squeeze Worth the Ooze?

PMID- 27889847
TI  - Diagnostic Value of Small Bowel Capsule Endoscopy in Isolated Ileitis: A CAPENTRY
      Study.
AB  - BACKGROUND: Capsule endoscopy (CE) has proven to be highly effective at detecting
      small bowel lesions, but studies regarding the diagnostic impact of CE on ileitis
      are rare. AIMS: We evaluated the diagnostic value of small bowel CE for isolated
      ileitis observed during ileocolonoscopy. METHODS: The CE results in 137 patients
      initially diagnosed with ileitis without colonic mucosal abnormalities on
      ileocolonoscopy at one of eight tertiary referral centers between October 2002
      and June 2015 were retrospectively analyzed. RESULTS: Among the 137 patients with
      isolated ileitis observed on ileocolonoscopy, 117 (85.4%) revealed positive small
      bowel CE findings (85.4%). The rate of positive small bowel CE findings was 92.9%
      in cases of ileal aphthous ulcer or erosion, and 90.9% in cases of ileal ulcer.
      Among 117 positive CE cases, the most common final diagnosis by CE was Crohn's
      disease (CD) (n = 44, 32%). No findings were identified in 20 (14.6%) of 137
      cases. Ileal erosion/ulcer, rather than findings such as nodularity and erythema
      or elevated erythrocyte sedimentation rate (ESR) (>10 mm/h), was significant
      predictive factors for positive CE findings in multivariate analysis.
      CONCLUSIONS: Small bowel CE showed a high diagnostic yield (85.4%) in symptomatic
      patients with isolated ileitis on ileocolonoscopy. Erosion or ulcer of the small
      bowel was a common finding on CE (66.4%), and approximately one-third of patients
      were diagnosed with CD. In patients with isolated ileitis on ileocolonoscopy, CE
      should be considered to evaluate small bowel lesions when the patient shows an
      elevated ESR or when the ileitis manifests as ileal ulcer or erosion rather than
      a nodular or erythematous lesion.

PMID- 27889849
TI  - Principles of managing Vancouver type B periprosthetic fractures around cemented
      polished tapered femoral stems.
AB  - The management of periprosthetic fractures around total hip replacements is a
      complex and challenging problem. Getting it right first time is an important
      factor in reducing the morbidity, mortality and financial burden associated with
      these injuries. Understanding and applying the basic principles of fracture
      management helps increase the chance of successful treatment. Based on these
      principles, we suggest a treatment algorithm for managing periprosthetic
      fractures around polished tapered femoral stems.

PMID- 27889848
TI  - Changes of ammonia, urea contents and transaminase activity in the body during
      aerial exposure and ammonia loading in Chinese loach Paramisgurnus dabryanus.
AB  - The Paramisgurnus dabryanus was exposed to 30 mmol L-1 NH4Cl solution and air to
      assessing the change of body ammonia and urea contents and the activities of
      alanine aminotransferase (ALT) and aspartate transaminase (AST). After 48 h of
      ammonia exposure, ammonia concentration in the plasma, brain, liver and muscle
      were 3.3-fold, 5.6-fold, 3.5-fold and 4.2-fold, respectively, those of the
      control values. Plasma, brain, liver and muscle ammonia concentrations increased
      to 2.2-fold, 3.3-fold, 2.5-fold and 2.9-fold, respectively, those of control
      values in response to 48 h of aerial exposure. Within the given treatment
      (ammonia or aerial exposure), there was no change in plasma, brain and liver urea
      concentrations between exposure durations. The plasma ALT activity was
      significantly affected by exposure time during aerial exposure, while the liver
      ALT activity was not affected by ammonia or aerial exposure. Exposure to NH4Cl or
      air had no effect on either plasma or liver AST activity. Our results suggested
      that P. dabryanus could accumulate quite high level of internal ammonia because
      of the high ammonia tolerance in its cells and tissues, and NH3 volatilization
      would be a possible ammonia detoxification strategy in P. dabryanus. Urea
      synthesis was not an effective mechanism to deal with environmental or internal
      ammonia problem. The significant increase of ALT activity in plasma during aerial
      exposure, indicating that alanine synthesis through certain amino acid catabolism
      may be subsistent in P. dabryanus.

PMID- 27889850
TI  - Chemical fractionation and health risk assessment of particulate matter-bound
      metals in Pune, India.
AB  - The present study deals with the assessment of sequential extraction of
      particulate matter (PM)-bound metals and the potential health risks associated
      with them in a growing metropolitan city (Pune) of India. The average mass
      concentration of both PM2.5-10 and PM2.5 exceeded the National Ambient Air
      Quality Standards. Significant seasonal variation in mass concentration was found
      for both size fractions of PM with higher values in winter season and lower in
      monsoon. Chemical species of the studied trace metals in PM exhibited significant
      differences, due to difference in sources of pollution. Metals such as Cd, Pb,
      and Cr in both size fractions and Zn and Co in fine fraction were more
      efficiently extracted in mobile fractions showing their mobile nature while Ni
      and Fe showed reduced mobility. Fe showed the highest concentrations among all
      the analyzed elements in both coarse (PM2.5-10) and fine (PM2.5) PM, while Cd
      showed least concentration in both size fractions. PCA identified industrial
      emissions, vehicular activity, coal combustion, diesel exhaust, waste
      incineration, electronic waste processing, constructional activities, soil, and
      road dust as probable contributors responsible for the metallic fraction of PM.
      All the metals showed varying contamination in PM samples. The contamination was
      higher for fine particles than coarse ones. The average global contamination
      factor was found to be 27.0-34.3 in coarse and fine PM, respectively. The hazard
      quotient (HQ) estimated for Cd, Co, and Ni (both total and easily accessible
      concentrations) exceeded the safe level (HQ = 1), indicating that these metals
      would result in non-carcinogenic health effects to the exposed population. The HQ
      ranged from 9.1 * 10-5 for Cu (coarse) to 8.3 for Ni (fine) PM. The cancer risk
      for Cd, Ni, and Cr in both sized PM were much higher than the acceptable limits
      of USEPA.

PMID- 27889851
TI  - Effect of cow colostrum on the performance and survival rate of local newborn
      piglets in Benin Republic.
AB  - The effect of bovine colostrum, including its thermally labile compounds, on the
      survival and growth performance of local breed piglets reared by their mother, in
      Benin, was evaluated over a 49-day trial. Three groups of 16 piglets, stemming
      from two primiparous sows belonging to a unique traditional farm, were
      respectively fed for the first 48 h of life with either bovine colostrum heated
      to 85  degrees C for 30 min, or thawed bovine colostrum, or colostrum from the
      mother. Thereafter, the animals that received bovine colostrum turned back to
      their mother. At day 21, almost all piglets from the group that received heated
      colostrum died. The highest total weight gain was obtained in the group that
      received thawed bovine colostrum (P ? 0.01), followed by the group left with the
      mother. Corresponding average daily gains (ADGs) were 56, 34 and 2 g/day,
      respectively (P ? 0.05). At the end of the trial, the treatment effect was highly
      significant on the survival of piglets (100% in the thawed colostrum group vs. 00
      and 50%, respectively, in the heated colostrum group and in the group left with
      the mother). At day 49, numerically higher weight and ADGs were obtained in the
      group that received thawed cow colostrum. Thawed bovine colostrum improved the
      growth performance and piglet survival in the local pig breed in Benin, probably
      owing to thermally labile components. Bovine colostrum may be used in our farms
      in order to reduce pre-weaning mortality, improve the profitability of livestock
      farmers, and ensure survival of traditional farms. The use of bovine colostrum on
      farms could be facilitated by collaboration between pig farmers and bovine
      farmers. It could also be facilitated by the creation of a colostrum bank.

PMID- 27889852
TI  - Effects of stiffness and volume on the transit time of an erythrocyte through a
      slit.
AB  - By using a fully coupled fluid-cell interaction model, we numerically simulate
      the dynamic process of a red blood cell passing through a slit driven by an
      incoming flow. The model is achieved by combining a multiscale model of the
      composite cell membrane with a boundary element fluid dynamics model based on the
      Stokes flow assumption. Our concentration is on the correlation between the
      transit time (the time it takes to finish the whole translocation process) and
      different conditions (flow speed, cell orientation, cell stiffness, cell volume,
      etc.) that are involved. According to the numerical prediction (with some
      exceptions), the transit time rises as the cell is stiffened. It is also highly
      sensitive to volume increase inside the cell. In general, even slightly swollen
      cells (i.e., the internal volume is increased while the surface area of the cell
      kept unchanged) travel dramatically slower through the slit. For these cells,
      there is also an increased chance of blockage.

PMID- 27889853
TI  - Photo-Physical Behavior and Fluorescence of Thermo Switchable Nanocomposite Based
      on Methyl Methacrylate -Spirobenzopyran.
AB  - Nanocomposites with thermo and photo-switchable fluorescent properties were
      synthesized via mini-emulsion polymerization based on spiropyran and methyl
      methacrylate monomer. The photophysical behavior of fluorescence nanocomposites
      was investigated by fluorescence spectrophotometry in different temperature, UV
      light and time of exposure. It was found that methyl methacrylate polymer is
      capable of acting as a protective layer and play a critical role in improving the
      photostability of colorants. The nanocomposites exhibited excellent fluorescent
      thermo-switching action with respect to the free spiro molecule. Graphical
      Abstract ?.

PMID- 27889854
TI  - Do we have a moral responsibility to compensate for vulnerable groups? A
      discussion on the right to health for LGBT people.
AB  - Vulnerability is a broad concept widely addressed in recent scholarly literature.
      Lesbian, gay, bisexual, and transgender (LGBT) people are among the vulnerable
      populations with significant disadvantages related to health and the social
      determinants of health. Medical ethics discourse tackles vulnerability from
      philosophical and political perspectives. LGBT people experience several
      disadvantages from both perspectives. This article aims to justify the right to
      health for LGBT people and their particular claims regarding healthcare because
      they belong to a vulnerable group. Rawls' theory of justice and Norman Daniels'
      normal functioning approach will be discussed in this context. Despite the fact
      that the right to health can be justified by Daniels' normal functioning
      approach, there is still a theoretical gap in justifying the right to health for
      particular vulnerable populations such as LGBT peopleand discussing society's
      duty to compensate for these disadvantages. In search of solid theoretical
      grounds for the justification of the right to health for LGBT people, the present
      author takes the opportunity to utilize Daniels' flexible definition of normal
      functioning to show that normal functioning not only varies by age but also by
      different states of human existence, including sexual orientation and gender
      identity, and to propose replacing the life span approach with normal states of
      human existence.

PMID- 27889855
TI  - Epigallocatechin Gallate Attenuates beta-Amyloid Generation and Oxidative Stress
      Involvement of PPARgamma in N2a/APP695 Cells.
AB  - The accumulation of beta-amyloid (Abeta) peptide plaques is a major pathogenic
      event in Alzheimer's disease (AD). Abeta is a cleaved fragment of APP via BACE1,
      which is the rate-limiting enzyme in APP processing and Abeta generation. Nuclear
      receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is
      considered to be a potential target for AD treatment, because of its potent
      antioxidant and inhibitory effects on Abeta production by negatively regulating
      BACE1. Epigallocatechin gallate (EGCG), a highly active catechin found in green
      tea, is known to enhance metabolic activity and cognitive ability in the mice
      model of AD. To investigate whether the therapeutic effect of EGCG is related to
      the PPARgamma pathway, we analysed the alterations in the intracellular molecular
      expression of PPARgamma after EGCG treatment in the N2a/APP695 cell line. In this
      study, we observed that EGCG attenuated Abeta generation in N2a/APP695 cells,
      such as the PPARgamma agonist, pioglitazone, by suppressing the transcription and
      translation of BACE1 and that its effect was attenuated by the PPARgamma
      inhibitor, GW9662. Intriguingly, EGCG significantly reinforced the activity of
      PPARgamma by promoting its mRNA and protein expressions in N2a/APP695 cells.
      Moreover, EGCG also decreased the expression of pro-apoptotic proteins (Bax,
      caspase-3), reduced the activity of the anti-inflammatory agent NF-kappaB and
      inhibited the oxidative stress by decreasing the levels of ROS and MDA and
      increasing the expression of MnSOD. Co-administration of GW9662 also
      significantly decreased the EGCG-mediated neuroprotective effect evidenced by the
      increase in oxidative stress and inflammatory markers. The therapeutic efficacy
      of EGCG in AD may be derived from the up-regulation of PPARgamma mRNA and protein
      expressions.

PMID- 27889858
TI  - The Pursuit of Truth in the Company of Friends : In Memorium: Charles W. Daniel.

PMID- 27889857
TI  - Accurate Control of 17beta-Estradiol Long-Term Release Increases Reliability and
      Reproducibility of Preclinical Animal Studies.
AB  - Estrogens are the subject of intensive researches aiming to elucidate their
      mechanism of action on the various tissues they target and especially on mammary
      gland and breast cancer. The use of ready-to-use slow releasing devices to
      administer steroids, especially estrogens, to small experimental animals remains
      the method of choice in terms of animal well-being and of safety for both the
      researcher and the animal. In this study, we evaluated and compared, in vitro and
      in vivo, the release kinetic of estradiol (E2) over sixty days from two different
      slow-releasing systems: the matrix pellet (MP) and the reservoir implant (RI). We
      compared the impact of these systems in three E2-sensitive mouse models : mammary
      gland development, human MCF7 adenocarcinoma xenograft and mouse melanoma
      progression. The real amount of E2 that is released from both types of devices
      could differ from manufacturer specifications due to inadequate release for MP
      and initial burst effect for RI. Compared to MP, the interindividual variability
      was reduced with RI thanks to a superior control of the E2 release. Depending on
      the dose-dependent sensitivity of the physiological or pathological readout
      studied, this could lead to an improvement of the statistical power of in vivo
      experiments and thus to a reduction of the required animal number. Altogether,
      our data draw attention on the importance to adequately select the slow-releasing
      device that is the most appropriated to a specific experiment to better fulfill
      the 3Rs rule (Replacement, Reduction, Refinement) related to animal welfare and
      protection.

PMID- 27889856
TI  - Gender Differences in Anxiety Trajectories from Middle to Late Adolescence.
AB  - Although developmental trajectories of anxiety symptomatology have begun to be
      explored, most research has focused on total anxiety symptom scores during
      childhood and early adolescence, using racially/ethnically homogenous samples.
      Understanding the heterogeneous courses of anxiety disorder symptoms during
      middle to late adolescence has the potential to clarify developmental risk models
      of anxiety and to inform prevention programs. Therefore, this study specifically
      examined gender differences in developmental trajectories of anxiety disorder
      symptoms (generalized anxiety disorder, panic disorder, and social anxiety
      disorder) from middle to late adolescence in a diverse community sample (N =
      1000; 57 % female; 65 % White), assessed annually over 2 years. Latent growth
      curve modeling revealed that girls exhibited a slight linear decrease in
      generalized anxiety disorder, panic disorder, and social anxiety disorder
      symptoms, whereas boys exhibited a stable course. These models suggested that one
      trajectory was appropriate for panic disorder symptoms in both girls and boys.
      Growth mixture models indicated the presence of four latent generalized anxiety
      disorder symptom trajectory classes: low increasing, moderate decreasing
      slightly, high decreasing, and very high decreasing rapidly. Growth mixture
      models also suggested the presence of five latent social anxiety disorder symptom
      trajectory classes: a low stable trajectory class and four classes that were
      qualitatively similar to the latent generalized anxiety disorder trajectories.
      For both generalized anxiety disorder and social anxiety disorder symptoms, girls
      were significantly more likely than boys to be in trajectory classes
      characterized by moderate or high initial symptoms that subsequently decreased
      over time. These findings provide novel information regarding the developmental
      course of anxiety disorder symptoms in adolescents.

PMID- 27889859
TI  - Chronic high-dose glucocorticoid therapy triggers the development of chronic
      organ damage and worsens disease outcome in systemic lupus erythematosus.
AB  - Long-term survival of patients with systemic lupus erythematosus (SLE) improved
      worldwide; thus, prevention of cumulative organ damage became a major goal in
      disease management. The aim of our study was to investigate the chronic organ
      damages and their influence on disease outcome in SLE. We evaluated clinical
      conditions, laboratory findings and medications of 357 consecutive SLE patients
      and assessed their impact on Systemic Lupus Collaborating Clinics
      (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI) and disease
      outcome. We detected one or more SDI scores in 77.87% of patients. Patients with
      disease duration of more than 10 years and subjects diagnosed at age above 40 had
      significantly higher SDI values. The most frequent damages were valvulopathies,
      cognitive dysfunction, angina pectoris and venous thrombosis. Higher cumulative
      glucocorticoid dose increased SDI, while chloroquin treatment was favourable for
      patients. Male gender, elevated SDI scores and higher cumulative doses of
      glucocorticoids increased mortality risk. Our data confirmed that disease
      duration, age at diagnosis and chronic high-dose glucocorticoid therapy have
      significant effects on the development of chronic organ damage. Higher SDI score
      is characterized with worse survival ratios. The most common chronic organ
      damages affected the cardiovascular or neuropsychiatric system. As long-term
      survival in SLE improves, it becomes increasingly important to identify the
      determinants of chronic organ damage. Most of the chronic organ damage occurs in
      the cardiovascular and the neuropsychiatric systems; thus, regular follow-up,
      screening and adequate therapy are essential for the best clinical outcome.

PMID- 27889860
TI  - Rich but poor: life in the Roman period with extreme rheumatoid arthritis.
AB  - In a Sidonian sarcophagus, from the Late Antique/early Christian period, skeletal
      remains of two persons were found. One of them, male, 30-50 years old, was found
      almost completely ankylosed, with highly osteoporotic bones and prominent erosion
      of joint surfaces. We diagnosed rheumatoid arthritis based on the eroded odontoid
      process, mandibular condyles, distal humerus, proximal and distal ulna, as well
      ankylosed hand and foot bones. Despite the fact that ankyloses of vertebrae and
      sacroiliac joint could point towards ankylosing spondylitis, the lack of typical
      vertebral ankyloses and new bone formation led to exclusion. In a practical
      sense, due to the advanced stage of the disease, the man was fixed in the supine
      position, on the left, with his head turned to the right. Apparently, he could
      not move and had problems with chewing and breathing. But, the high standard of
      provided healthcare probably enabled him to survive in advanced stages of the
      disease. This case shed light on the antiquity of the disease, its medical, and
      social context and provided the example of most extreme osteological changes
      reported in the paleopathological and medical literature.

PMID- 27889862
TI  - Erratum to: Botulinum toxin and rehabilitation treatment in inclusion body
      myositis for severe oropharyngeal dysphagia.

PMID- 27889861
TI  - Synchronized navigation of current and prior studies using image registration
      improves radiologist's efficiency.
AB  - PURPOSE: The purpose of this study was to investigate how the use of multi-modal
      rigid image registration integrated within a standard picture archiving and
      communication system affects the efficiency of a radiologist while performing
      routine interpretations of cases including prior examinations. METHODS: Six
      radiologists were recruited to read a set of cases (either 16 neuroradiology or
      14 musculoskeletal cases) during two crossover reading sessions. Each radiologist
      read each case twice, one time with synchronized navigation, which enables
      spatial synchronization across examinations from different study dates, and one
      time without. Efficiency was evaluated based upon time to read a case and amount
      of scrolling while browsing a case using Wilcoxon signed rank test. RESULTS:
      Significant improvements in efficiency were found considering either all
      radiologists simultaneously, the two sections separately and the majority of
      individual radiologists for time to read and for amount of scrolling. The
      relative improvement for each individual radiologist ranged from 4 to 32% for
      time to read and from 14 to 38% for amount of scrolling. CONCLUSION: Image
      registration providing synchronized navigation across examinations from different
      study dates provides a tool that enables radiologists to work more efficiently
      while reading cases with one or more prior examinations.

PMID- 27889863
TI  - Genetic association study between RIT2 and Parkinson's disease in a Han Chinese
      population.
AB  - Recent several meta-analyses and certain case-control studies suggested that the
      Ras-like without CAAX 2 (RIT2) rs12456492 increased the risk of Parkinson's
      disease (PD) in Asian and Caucasian populations. However, as so far, the
      association between RIT2 rs12456492 and PD is still controversial. We
      investigated genetic association of RIT2 rs12456492 with PD susceptibility in a
      Han Chinese population of 1747 ethnic Han Chinese subjects comprising 884 PD
      patients and 863 healthy controls. The minor allele frequency (MAF) of G at the
      RIT2 rs12456492 was not significantly different between the cases and the
      controls. Furthermore, no significant differences were observed in genotype
      distribution between PD patients and healthy controls for the RIT2 rs12456492,
      even after being stratified by age at onset and gender. In addition, we found
      that no significant differences were detected in the clinical manifestations for
      gender, age at onset, and onset symptoms between PD patients with AG + GG
      genotypes and those with AA genotypes. Our study from the mainland China
      demonstrates that RIT2 rs12456492 do not increase the risk of developing PD.
      Therefore, more replication studies in additional Chinese population and other
      cohorts are warranted to further clarify the role of RIT2 rs12456492 in PD
      susceptibility.

PMID- 27889864
TI  - Erratum to: Synergism between Enantiomers Creates Species-Specific Pheromone
      Blends and Minimizes Cross-Attraction for Two Species of Cerambycid Beetles.

PMID- 27889865
TI  - Does Plant Cultivar Difference Modify the Bottom-Up Effects of Resource
      Limitation on Plant-Insect Herbivore Interactions?
AB  - Variation in resource input to plants triggers bottom-up effects on plant-insect
      herbivore interactions. However, variation in plant intrinsic traits in response
      to resource availability may modify the bottom-up effects. Furthermore, the
      consequences also may depend on the feeding strategy of insect herbivores
      belonging to different feeding guilds. We evaluated the performance of two insect
      herbivores from distinct feeding guilds, the leaf miner Tuta absoluta and the
      phloem feeder Bemisia tabaci. We offered the insects two tomato cultivars growing
      under optimal nitrogen input vs. nitrogen limitation, or under optimal water
      input vs. water limitation. We found that: (i) the two cultivars differed in
      their responses to nitrogen and water limitation by regulating primary (leaf-gas
      exchange related parameters, leaf nitrogen content, and leaf C/N ratio) and
      secondary metabolism (main defensive compounds: glycoalkaloids); (ii) for both
      plant cultivars, nitrogen or water limitation significantly affected T. absoluta
      survival and development, while B. tabaci survival was affected only by nitrogen
      limitation; and surprisingly (iii) plant cultivar differences did not modify the
      negative bottom-up effects of resource limitation on the two insect herbivores.
      In conclusion, the negative effects of resource limitation cascaded up to insect
      herbivores even though plant cultivars exhibited various adaptive traits to
      resource limitation.

PMID- 27889866
TI  - Management and outcomes of obstructive sleep apnea in children with Robin
      sequence, a cross-sectional study.
AB  - OBJECTIVE: The objective of this cross-sectional study is to assess the
      prevalence, course, and management of obstructive sleep apnea (OSA) in children
      with Robin sequence (RS) aged 1-18 years. MATERIALS AND METHODS: A cross
      sectional study was conducted in 63 children aged 1 to18 years with RS. Patient
      data were collected on baseline characteristics and management. OSA was evaluated
      by polysomnography. RESULTS: Sixty-three children with RS were included (median
      age 8.0 years) and divided into two groups based on the initial treatment: prone
      positioning or respiratory support. Respiratory support was more often indicated
      in children with a non-isolated RS (p < 0.05). At cross section, in the prone
      positioning group (n = 32), one child was diagnosed with OSA. In the respiratory
      support group (n = 31), 13 children (42 %) had respiratory problems of whom 10
      needed respiratory support. CONCLUSIONS: Between the age of 1 and 18 years,
      almost one out of four children with RS still has respiratory problems. Children
      with RS, who can be treated with prone positioning only as an infant, are not
      likely to develop obstructive airway problems at a later age. In contrast,
      children who need respiratory support early after birth are at risk of continuing
      or re-developing OSA after the age of 1 year. CLINICAL RELEVANCE: This study
      shows that those who need respiratory support at an early age need careful
      monitoring until adulthood.

PMID- 27889867
TI  - The impact of younger age on treatment discontinuation in insured IVF patients.
AB  - PURPOSE: This retrospective cohort study aimed to determine whether age
      influences treatment discontinuation among insured patients undergoing in vitro
      fertilization (IVF). We hypothesized that the youngest patients would be the
      least likely to discontinue treatment. METHODS: All women age 18-42 who underwent
      their first fresh, non-donor IVF cycle from 2002 to 2013 were followed until a
      live birth was achieved, until they discontinued treatment at our center (not
      presenting for treatment for a one-year period), or until they completed six
      fresh or frozen embryo transfer cycles, whichever occurred first. RESULTS: Of
      11,361 women included, 4336 (38.2 %) discontinued treatment at our center before
      achieving a live birth or undergoing six IVF cycles. Discontinuation differed by
      age for cycles 2-4 (all P <= 0.004), with the proportion among women age 40-42
      averaging 6-7 % higher than the other groups; discontinuation per cycle was
      similar among women <30 compared to women age 30-<35 and 35-<40. This continued
      in cycles 5 and 6, and in the sixth, 35.2, 32.0, 32.3, and 40.2 % of women among
      the four age groups discontinued treatment, respectively (P = 0.17). In cycles 2
      5, women in the oldest two age groups with secondary infertility consistently
      discontinued treatment more frequently than those with primary infertility.
      CONCLUSIONS: We found that women in the oldest age group were more likely to
      discontinue IVF treatment than younger women. Surprisingly, we found that the
      youngest women discontinued treatment in a similar fashion to women age 30-<40.

PMID- 27889868
TI  - Biobanking of different body fluids within the frame of IVF-a standard operating
      procedure to improve reproductive biology research.
AB  - PURPOSE: The aim of the present study was to develop a standard operating
      procedure (SOP) for the collection, transport, and storage of human cumulus
      cells, follicular fluid, blood serum, seminal plasma, embryo culture supernatant,
      and embryo culture supernatant control obtained within the IVF process under
      approved protocols and written informed consent from participating patients. The
      SOP was developed at the Kinderwunsch Institut Schenk, Dobl, Austria, together
      with Biobank Graz of the Medical University of Graz, Austria. METHODS: The SOP
      provides comprehensive details of laboratory procedures and sampling of the
      different fluids within the IVF process. Furthermore, information on sample
      coding, references of involved laboratory techniques (e.g., oocyte retrieval with
      a Steiner-TAN needle), ethical approvals, and biobanking procedures are
      presented. RESULTS: The result of the present study is a standard operating
      procedure. CONCLUSIONS: The SOP ensures a professional way for collection and
      scientific use of IVF samples by the Kinderwunsch Institut Schenk, Dobl, Austria,
      and Biobank Graz of the Medical University of Graz, Austria. It can be used as a
      template for other institutions to unify specimen collection procedures in the
      field of reproductive health research.

PMID- 27889870
TI  - Secretory Expression, Purification, Characterization, and Application of an
      Aspergillus oryzae Prolyl Aminopeptidase in Bacillus subtilis.
AB  - cDNA coding a prolyl aminopeptidase (PAP) was cloned from Aspergillus oryzae and
      over expressed in Bacillus subtilis with a 6*His tag in N-terminus. The
      recombinant prolyl aminopeptidase was secreted to extracellular by adding 2 mM
      CaCl2 and 5% D-sorbitol in TB medium; the enzyme activity in fermented
      supernatant increased from 7.2 to 41.5 U mL-1. It has been purified 4.3-fold
      through Ni-chelating affinity chromatography with a recovery of 47.3%. The
      purified enzyme is stable below 50  degrees C and within pH 6-11, and with the
      highest activity at pH 7.5 and 50  degrees C. Several kinds of salt can activate
      enzyme activity in a certain concentration and the relative activity was 127.02%
      even when the concentration of NaCl reached 4.36 M. It cleaved N-terminal Pro
      residues from many peptides but shown different hydrolysis rates for various Pro
      X dipeptides or peptides which are of different lengths. It combined with
      alkaline protease and leucine aminopeptidase to hydrolyze casein, many free amino
      acid especially proline and small peptide of hydrolysate increased significantly.

PMID- 27889871
TI  - Genetic Relationships and Spatial Genetic Structure Among Populations of Rhodnius
      prolixus (Hemiptera: Reduviidae) in Colombia and Venezuela Based on Mitochondrial
      Cytochrome-b Sequences.
AB  - One hundred twenty Rhodnius prolixus (Stal) (Hemiptera: Reduviidae) specimens
      from 6 Colombian Departments and 1 Venezuelan State had 594-bp of the
      mitochondrial cytochrome-b gene sequenced to improve the understanding of
      evolutionary processes that shape the main vector of Chagas disease. The levels
      of genetic diversity for this species were low-medium with reference to other
      bugs. The genetic heterogeneity among the populations was very limited which
      means there has been extensive gene flow and/or very recent split processes. The
      overall sample as well as some individual populations showed evidence of recent
      population expansions (with the exception of Arauca, which yielded evidence of a
      bottleneck for a mismatch distribution). This expansion (11,000 or 2000-25,000
      year ago depending of two procedures employed) coincides with the ending of the
      last intense glacial conditions during the Pleistocene and the beginning of the
      Holocene that had a warmer and wetter climate. Some of our autocorrelation
      analyses (AIDA and Genetic Landscape Interpolation Analysis) indicated local
      patches of high genetic similarity but no globally significant spatial structure.
      We did show an original haplotype distributed throughout the entirety of the
      geographical area studied.

PMID- 27889869
TI  - Left Ventricular Speckle Tracking-Derived Cardiac Strain and Cardiac Twist
      Mechanics in Athletes: A Systematic Review and Meta-Analysis of Controlled
      Studies.
AB  - BACKGROUND: The athlete's heart is associated with physiological remodeling as a
      consequence of repetitive cardiac loading. The effect of exercise training on
      left ventricular (LV) cardiac strain and twist mechanics are equivocal, and no
      meta-analysis has been conducted to date. OBJECTIVE: The objective of this
      systematic review and meta-analysis was to review the literature pertaining to
      the effect of different forms of athletic training on cardiac strain and twist
      mechanics and determine the influence of traditional and contemporary sporting
      classifications on cardiac strain and twist mechanics. METHODS: We searched
      PubMed/MEDLINE, Web of Science, and ScienceDirect for controlled studies of aged
      matched male participants aged 18-45 years that used two-dimensional (2D) speckle
      tracking with a defined athlete sporting discipline and a control group not
      engaged in training programs. Data were extracted independently by two reviewers.
      Random-effects meta-analyses, subgroup analyses, and meta-regressions were
      conducted. RESULTS: Our review included 13 studies with 945 participants
      (controls n = 355; athletes n = 590). Meta-analyses showed no athlete-control
      differences in LV strain or twist mechanics. However, moderator analyses showed
      greater LV twist in high-static low-dynamic athletes (d = -0.76, 95% confidence
      interval [CI] -1.32 to -0.20; p < 0.01) than in controls. Peak untwisting
      velocity (PUV) was greater in high-static low-dynamic athletes (d = -0.43, 95% CI
      -0.84 to -0.03; p < 0.05) but less than controls in high-static high-dynamic
      athletes (d = 0.79, 95% CI 0.002-1.58; p = 0.05). Elite endurance athletes had
      significantly less twist and apical rotation than controls (d = 0.68, 95% CI 0.19
      1.16, p < 0.01; d = 0.64, 95% CI 0.27-1.00, p = 0.001, respectively) but no
      differences in basal rotation. Meta-regressions showed LV mass index was
      positively associated with global longitudinal (b = 0.01, 95% CI 0.002-0.02; p <
      0.05), whereas systolic blood pressure was negatively associated with PUV (b = 
      0.06, 95% CI -0.13 to -0.001; p = 0.05). CONCLUSION: Echocardiographic 2D speckle
      tracking can identify subtle physiological differences in adaptations to cardiac
      strain and twist mechanics between athletes and healthy controls. Differences in
      speckle tracking echocardiography-derived parameters can be identified using
      suitable sporting categorizations.

PMID- 27889872
TI  - Cascade Classification with Adaptive Feature Extraction for Arrhythmia Detection.
AB  - Detecting arrhythmia from ECG data is now feasible on mobile devices, but in this
      environment it is necessary to trade computational efficiency against accuracy.
      We propose an adaptive strategy for feature extraction that only considers
      normalized beat morphology features when running in a resource-constrained
      environment; but in a high-performance environment it takes account of a wider
      range of ECG features. This process is augmented by a cascaded random forest
      classifier. Experiments on data from the MIT-BIH Arrhythmia Database showed
      classification accuracies from 96.59% to 98.51%, which are comparable to state-of
      the art methods.

PMID- 27889874
TI  - Decision Support Provided by a Temporally Oriented Health Care Assistant : An
      Implementation of Computer-Interpretable Guidelines.
AB  - The automatic interpretation of clinical recommendations is a difficult task,
      even more so when it involves the processing of complex temporal constraints. In
      order to address this issue, a web-based system is presented herein. Its
      underlying model provides a comprehensive representation of temporal constraints
      in Clinical Practice Guidelines. The expressiveness and range of the model are
      shown through a case study featuring a Clinical Practice Guideline for the
      diagnosis and management of colon cancer. The proposed model was sufficient to
      represent the temporal constraints in the guideline, especially those that
      defined periodic events and placed temporal constraints on the assessment of
      patient states. The web-based tool acts as a health care assistant to health care
      professionals, combining the roles of focusing attention and providing patient
      specific advice.

PMID- 27889873
TI  - Information Technology-Based Interventions to Improve Drug-Drug Interaction
      Outcomes: A Systematic Review on Features and Effects.
AB  - The purpose of this systematic review was to identify features and effects of
      information technology (IT)-based interventions on outcomes related to drug-drug
      interactions (DDI outcomes). A literature search was conducted in Medline,
      EMBASE, and the Cochrane Library for published English-language studies. Studies
      were included if a main outcome was related to DDIs, the intervention involved an
      IT-based system, and the study design was experimental or observational with
      controls. Study characteristics, including features and effects of IT-based
      interventions, were extracted. Nineteen studies comprising five randomized
      controlled trials (RCT), five non-randomized controlled trials (NRCT) and nine
      observational studies with controls (OWC) were included. Sixty-four percent of
      prescriber-directed interventions, and all non-prescriber interventions, were
      effective. Each of the following characteristics corresponded to groups of
      studies of which a majority were effective: automatic provision of
      recommendations within the providers' workflow, intervention at the time of
      decision-making, integration into other systems, and requiring the reason for not
      following the recommendations. Only two studies measured clinical outcomes: an
      RCT that showed no significant improvement and an OWC that showed improvement,
      but did not statistically assess the effect. Most studies that measured surrogate
      outcomes (e.g. potential DDIs) and other outcomes (e.g. adherence to alerts)
      showed improvements. IT-based interventions improve surrogate clinical outcomes
      and adherence to DDI alerts. However, there is lack of robust evidence about
      their effectiveness on clinical outcomes. It is recommended that researchers
      consider the identified features of effective interventions in the design of
      interventions and evaluate the effectiveness on DDI outcomes, particularly
      clinical outcomes.

PMID- 27889875
TI  - Development of an Educational Program Integrating Concepts of Genetic Risk and
      Preventive Strategies for Children with a Family History of Melanoma.
AB  - Efforts to prevent melanoma, especially for those at elevated risk for the
      disease, should ideally begin during childhood. However, there are few preventive
      interventions targeting children who are at higher risk for melanoma due to a
      family history of the disease. Further, there are no educational interventions
      that aim to help these at-risk children understand their risk for melanoma and
      the ways in which preventive behaviors, such as sun protection, can mitigate
      their risk. The current paper describes a multidisciplinary team's process for
      creating a developmentally appropriate educational intervention about melanoma
      risk and prevention for children ages 8-17 years who have a family history of
      melanoma. Drawing from the fields of dermatology, health behavior change and
      education, genetic risk communication, science education, and graphic arts, the
      multimedia intervention created covers key learning points relevant to
      understanding melanoma, the role of DNA damage in melanoma development, inherited
      risk factors for melanoma, environmental factors causing DNA damage, and methods
      for preventing DNA damage, such as sun protective behaviors. Lessons learned
      during the development of the educational intervention, particularly relevant to
      multidisciplinary team interactions, are discussed. Implications for future
      testing and refinement of the novel educational content are also reviewed.

PMID- 27889876
TI  - Population Pharmacokinetic-Pharmacodynamic Modeling of 5-Fluorouracil for
      Toxicities in Rats.
AB  - BACKGROUND AND OBJECTIVES: Myelosuppression is a dose-limiting toxicity of 5
      fluorouracil (5-FU). Predicting the inter- and intra-patient variability in
      pharmacokinetics and toxicities of 5-FU may contribute to the individualized
      medicine. This study aimed to establish a population pharmacokinetic
      pharmacodynamic model that could evaluate the inter- and intra-individual
      variability in the plasma 5-FU concentration, 5-FU-induced body weight loss and
      myelosuppression in rats. METHOD: Plasma 5-FU concentrations, body weight loss,
      and blood cell counts in rats following the intravenous administration of various
      doses of 5-FU for 4 days were used to develop the population pharmacokinetic
      pharmacodynamic model. RESULTS: The population pharmacokinetic model consisting
      of a two-compartment model with Michaelis-Menten elimination kinetics
      successfully characterized the individual and population predictions of the
      plasma concentration of 5-FU and provided credible parameter estimates. The
      estimates of inter-individual variability in maximal rate of saturable metabolism
      and residual variability were 8.1 and 22.0%, respectively. The population
      pharmacokinetic-pharmacodynamic model adequately described the individual
      complete time-course of alterations in body weight loss, erythrocyte, leukocyte,
      and lymphocyte counts in rats treated with various doses of 5-FU. The inter
      individual variability of the drug effects in the pharmacodynamic model for body
      weight loss was 82.6%, which was relatively high. The results of the present
      study suggest that not only individual fluctuations in the 5-FU concentration but
      also the cell sensitivity would affect the onset and degree of 5-FU-induced
      toxicity. CONCLUSION: This population pharmacokinetic-pharmacodynamic model could
      evaluate the inter- and intra-individual variability in drug-induced toxicity and
      guide the assessments of novel anticancer agents in drug development.

PMID- 27889878
TI  - Same-day identification and antibiotic susceptibility testing on positive blood
      cultures: a simple and inexpensive procedure.
AB  - Fast diagnostic tools are becoming a hot topic in microbiology, especially in the
      case of septic patients. Therefore, we attempted to develop a fast, inexpensive,
      accurate and easy method to identify bacteria and perform an antibiotic
      susceptibility test directly on positive blood cultures that could be used in a
      routine laboratory. A procedure based on centrifugation and washing steps was
      performed on 110 non-duplicated (including nine seeded) positive blood culture
      bottles. Direct identification (DID) and antimicrobial susceptibility testing
      (AST) was conducted on the pellet with the MALDI Biotyper and Phoenix,
      respectively. Identification (ID) to the species level was correct in 44/45 (97%)
      cases for Gram-negative bacteria and 44/56 (79%) cases for Gram-positive
      bacteria. In total, 98.9% of the AST results were identical to the routine
      laboratory result. No very major errors, four major errors and eight minor errors
      were detected. A reliable identification and a high AST agreement were obtained
      from blood cultures seeded with multi-resistant bacteria. We simulated the
      timeline of DID and demonstrated an identification and AST result within 24 h
      using Escherichia coli- and Staphylococcus aureus-positive blood cultures as
      examples. We developed an easy, fast and cheap method to generate reliable ID and
      AST results. Moreover, this method may be used to obtain results within 24 h
      after incubating the blood culture bottles in the microbiology lab.

PMID- 27889877
TI  - MALDI-TOF MS meets WGS in a VRE outbreak investigation.
AB  - The use of MALDI-TOF MS (matrix-assisted laser desorption/ ionization-time of
      flight mass spectrometry) and WGS (whole genome sequencing) has been described
      for identification and strain relatedness determination. We describe the
      complementary use of MALDI-TOF MS and WGS in a VRE (vancomycin-resistant
      enterococci) outbreak investigation, and discuss some of the challenges with
      defining strain similarity across these two platforms. Although both assays
      indicated multiple clusters involved in the outbreak of vancomycin resistant
      Enterococcus faecium isolates from positive blood cultures of four haematology
      oncology patients, the small cohort and discrepancies between findings indicate
      the limitations of MALDI-TOF MS and the cautious interpretation of MALDI-TOF MS
      dendrograms during outbreaks. For definitive determination of the evolutionary
      distance between isolates, WGS can be used.

PMID- 27889879
TI  - Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review
      with a focus on Mediterranean countries.
AB  - Quinolones are a family of synthetic broad-spectrum antimicrobial drugs. These
      molecules have been widely prescribed to treat various infectious diseases and
      have been classified into several generations based on their spectrum of
      activity. Quinolones inhibit bacterial DNA synthesis by interfering with the
      action of DNA gyrase and topoisomerase IV. Mutations in the genes encoding these
      targets are the most common mechanisms of high-level fluoroquinolone resistance.
      Moreover, three mechanisms for plasmid-mediated quinolone resistance (PMQR) have
      been discovered since 1998 and include Qnr proteins, the aminoglycoside
      acetyltransferase AAC(6')-Ib-cr, and plasmid-mediated efflux pumps QepA and
      OqxAB. Plasmids with these mechanisms often encode additional antimicrobial
      resistance (extended spectrum beta-lactamases [ESBLs] and plasmidic AmpC [pAmpC]
      beta-lactamases) and can transfer multidrug resistance. The PMQR determinants are
      disseminated in Mediterranean countries with prevalence relatively high depending
      on the sources and the regions, highlighting the necessity of long-term
      surveillance for the future monitoring of trends in the occurrence of PMQR genes.

PMID- 27889880
TI  - The impact of extended lymph node dissection versus neoadjuvant therapy with
      limited lymph node dissection on biochemical recurrence in high-risk prostate
      cancer patients treated with radical prostatectomy: a multi-institutional
      analysis.
AB  - The optimal treatment for high-risk prostate cancer (Pca) remains to be
      established. The current guidelines recommend extended pelvic lymph node
      dissection (e-PLND) for selected intermediate- and high-risk patients treated
      with RP. However, the indications, optimal extent, and therapeutic benefits of e
      PLND remain unclear. The aim of this study was to assess whether e-PLND confers
      an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing
      hormone-releasing hormone and estramustine (LHRH + EMP). The Michinoku Urological
      Cancer Study Group database contained the data of 2403 consecutive Pca patients
      treated with RP at four institutes between March 2000 and December 2014. In the e
      PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND,
      with lymphatic tissue removal around the obturator and the external iliac
      regions, and hypogastric lymph node dissection. The neoadjuvant therapy with
      limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP
      and removal of the obturator node chain between September 2005 and June 2014 at
      Hirosaki University. The outcome measure was BRFS. The 5-year biochemical
      recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and
      e-PLND group were 84.9 and 54.7%, respectively (P < 0.0001). The operative time
      was significantly longer in the e-PLND group compared to that of the neoadjuvant
      therapy with l-PLND group. Grade 3/4 surgery-related complications were not
      identified in both groups. Although the present study was not randomized,
      neoadjuvant LHRH + EMP therapy followed by RP might reduce the risk of
      biochemical recurrence.

PMID- 27889881
TI  - Identification of reference genes and miRNAs for qRT-PCR in human esophageal
      squamous cell carcinoma.
AB  - It is important to select an appropriate reference gene and miRNA when using
      quantitative real-time polymerase chain reaction (qRT-PCR) to analyze gene and
      miRNA expression. However, many commonly used reference genes and miRNAs are not
      stably expressed and therefore not suitable for normalization or quantification
      of qRT-PCR data. This study aims to identify appropriate reference genes and
      miRNAs for use in human esophageal squamous carcinoma qRT-PCR analysis. Using
      data provided by The Cancer Genome Atlas, we identified DDX5, LAPTM4A, P4HB,
      RHOA, miR-28-5p, miR-34a-5p, and miR-186-5p as candidate reference genes and
      miRNAs. We used qRT-PCR to verify the expression levels of these candidates and
      another seven commonly used reference genes and miRNAs. A set of 50 paired human
      normal esophageal tissues and squamous cell carcinoma samples were used in the
      analysis. We then used geNorm and NormFinder to analyze the results. DDX5,
      LAPTM4A, RHOA, ACTB, RNU48, miR-28-5p, miR-34a-5p, and miR-186-5p were stably
      expressed, indicating they are suitable for used as references in qRT-PCR
      analysis of esophageal squamous cell carcinoma. However, expression levels of 18s
      rRNA, GAPDH, P4HB, 5s rRNA, U6, and RNU6B varied greatly between esophageal
      normal and squamous cell carcinoma samples, indicating that they are not suitable
      for use as references in the qRT-PCR analysis of esophageal squamous cell
      carcinoma.

PMID- 27889882
TI  - True Incidence of Gleason 6 Pathology in Patients with Metastatic Castration
      Resistant Prostate Cancer (mCRPC).
AB  - INTRODUCTION: Recent evidence from histology studies regarding random prostate
      biopsies hint toward a relationship between higher biopsy Gleason score and the
      development of metastatic castration resistant prostate cancer (mCRPC). However,
      prostate biopsy underestimates final pathology in about one-third of patients. We
      evaluated the final whole gland pathology from radical prostatectomy exclusively
      in order to assess the true risk of progressing to the mCRPC state for patients
      with confirmed Gleason <=6 prostate cancer. METHODS: Patients with confirmed
      mCRPC from our outpatient clinic were retrospectively evaluated with regard to
      whole gland pathology and the occurrence of Gleason 6 histology from 1995 to
      2015. Conversely, patients with confirmed Gleason 6 pathology from our
      institutional database were followed up for the development of mCRPC from 2001 to
      2015. Kaplan-Meier analysis and the log rank test were applied for survival
      analysis. The binomial test was used to evaluate occurrence rates of Gleason <=6
      pathologies in mCRPC patients. RESULTS: Out of 62 patients with mCRPC none had
      confirmed Gleason 6 pathology on whole gland histology of the prostate. Out of 86
      patients with confirmed Gleason 6 pathology none developed an mCRPC over the
      follow-up period. CONCLUSION: The development of mCRPC in patients with true
      Gleason 6 pathology is very rare and could not be confirmed in our series. This
      finding may have important implications in future treatment planning.

PMID- 27889883
TI  - A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of
      Trypsin:Chymotrypsin as Compared to Serratiopeptidase and
      Trypsin:Bromelain:Rutoside in Wound Management.
AB  - INTRODUCTION: Systemic enzyme therapy can play an important role in maintaining
      normal inflammatory processes within the body and thereby helps support and speed
      up healing. In the course of the anti-inflammatory action, enzymes degrade
      damaged cells and necrotic material and, through the inactivation of mediators
      and toxic products, they restrict the edema and pain. METHOD: The study conducted
      at Grant Medical College, Mumbai, India was a clinical trial comparing the
      efficacy and tolerability of three oral enzyme treatment groups-oral tablets
      containing trypsin:chymotrypsin (TC) (Chymoral Forte(r)), serratiopeptidase (S) 5
      mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90
      mg, and rutoside 100 mg (TBR)-to evaluate their healing potential in surgical
      wounds after orthopedic surgery. RESULTS: A total of 75 patients were screened,
      randomized, and divided into three groups in 1:1:1 ratio receiving either of the
      three treatments. In the TC group, erythema was significantly reduced from 3.44
      on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction
      in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at
      each follow-up visit. Similarly reduction in the local irritation, wound
      discharge, edema, induration, and tenderness score with TC treatment at the end
      of the study was significantly higher than that observed in the other two groups.
      In addition TC showed significant reduction in pain on the VAS scale (p < 0.01).
      Global assessment of response to therapy for efficacy and tolerability was
      reported to be good to excellent in 88% and 92% of the patients on TC as compared
      to 12% and 8% with S and 12% and 8% with TBR. CONCLUSION: TC provides a better
      resolution of symptoms of inflammation after orthopedic surgery as compared to S
      and TBR, thus facilitating better wound healing. Further studies are warranted to
      confirm the findings. TRIAL REGISTRATION: Clinical Trial Registry of India (Reg.
      No. CTRI/2011/07/001920).

PMID- 27889884
TI  - Reduced density gradient as a novel approach for estimating QSAR descriptors, and
      its application to 1, 4-dihydropyridine derivatives with potential
      antihypertensive effects.
AB  - The relationship between the chemical structure and biological activity (log
      IC50) of 40 derivatives of 1,4-dihydropyridines (DHPs) was studied using density
      functional theory (DFT) and multiple linear regression analysis methods. With the
      aim of improving the quantitative structure-activity relationship (QSAR) model,
      the reduced density gradient s( r) of the optimized equilibrium geometries was
      used as a descriptor to include weak non-covalent interactions. The QSAR model
      highlights the correlation between the log IC50 with highest molecular orbital
      energy (E HOMO), molecular volume (V), partition coefficient (log P), non
      covalent interactions NCI(H4-G) and the dual descriptor [Deltaf(r)]. The model
      yielded values of R 2=79.57 and Q 2=69.67 that were validated with the next four
      internal analytical validations DK=0.076, DQ=-0.006, R P =0.056, and R N=0.000,
      and the external validation Q 2boot=64.26. The QSAR model found can be used to
      estimate biological activity with high reliability in new compounds based on a
      DHP series. Graphical abstract The good correlation between the log IC50 with the
      NCI (H4-G) estimated by the reduced density gradient approach of the DHP
      derivatives.

PMID- 27889885
TI  - Investigating Factors Involved in Post Laparoscopic Sleeve Gastrectomy (LSG)
      Neuropathy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity as the
      leading bariatric procedure for the treatment of morbid obesity. Due to the
      rising numbers of bariatric surgeries, neurologic complications have become
      increasingly recognized. Our aim was to examine biochemical and hormonal factors
      that are associated with neuropathy post-LSG. METHODS: Thirty-two patients were
      included: 16 patients with neuropathy in the neuropathic group (NG) and 16
      patients without neuropathy in the control group (CG). Diagnosis was made by a
      consultant neurologist, and blood samples were taken to examine vitamin
      deficiencies and hormones involved in neuropathy. RESULTS: There was no
      significant difference between the BMI (p = 0.1) in both groups as well as excess
      weight loss percentages post-LSG at 12 months (p = 0.6). B12 levels were within
      normal range, but higher in NG (p = 0.005). Vitamin B1 and B2 levels were
      significantly lower in NG; p values are 0.000 and 0.031, respectively. Vitamin B6
      levels were significantly higher in NG (p = 0.02) and copper levels were lower in
      NG (p = 0.009). There was no significant difference in GLP-1 response in both
      groups. CONCLUSION: Our data showed post-LSG neuropathy is associated with lower
      levels of vitamin B1, B2, and copper, plus patients who are older in age. Vitamin
      B6 was significantly higher in the NG, which is, at toxic levels, associated with
      neuropathy. No difference in preoperative BMI, excess weight loss percent at 1
      year, and GLP-1 levels was found. Larger data is required to validate our
      results.

PMID- 27889886
TI  - Association of midlife smoking status with change in processing speed and mental
      flexibility among HIV-seropositive and HIV-seronegative older men: the
      Multicenter AIDS Cohort Study.
AB  - Smoking is a potential risk factor for age-related cognitive decline. To date, no
      study has examined the association between smoking and cognitive decline in men
      living with human immunodeficiency virus (HIV). The aim of this present study is
      to examine whether smoking status and severity in midlife is associated with a
      rate of decline in cognitive processing speed among older HIV-seropositive and
      HIV-seronegative men who have sex with men. Data from 591 older HIV-seropositive
      and HIV-seronegative men who have sex with men from the Multicenter AIDS Cohort
      Study were examined. All participants had information on smoking history
      collected before age 50 years and at least 5 years of follow-up after age 50.
      Smoking history was categorized as never smoker, former smoker, and current
      smoker and cumulative pack years was calculated. The raw scores of three
      neuropsychological tests (Trail Making A, Trail Making B, and Symbol Digit
      Modalities tests) were log transformed (Trail Making A and B) and used in linear
      mixed models to determine associations between smoking history and at least
      subsequent 5-year decline in cognitive processing speed. There were no
      significant differences in the rates of neurological decline among never smokers,
      former smokers, and current smokers. Findings were similar among HIV-seropositive
      participants. However, an increase of 5 pack-years was statistically
      significantly associated with a greater rate of decline in the Trail Making Test
      B score and Composite Score (beta -0.0250 [95% CI, -0.0095 to -0.0006] and 
      0.0077 [95% CI, -0.0153 to -0.0002], respectively). We found no significant
      association between smoking treated as a categorical variable (never smoked,
      former smoker, or current smoker) and a small change in every increase of 5 pack
      years on measures of psychomotor speed and cognitive flexibility. To optimize
      healthy aging, interventions for smoking cessation should be tailored to men who
      have sex with men.

PMID- 27889888
TI  - Characteristics of ash and particle emissions during bubbling fluidised bed
      combustion of three types of residual forest biomass.
AB  - Combustion of residual forest biomass (RFB) derived from eucalypt (Eucalyptus
      globulus), pine (Pinus pinaster) and golden wattle (Acacia longifolia) was
      evaluated in a pilot-scale bubbling fluidised bed reactor (BFBR). During the
      combustion experiments, monitoring of temperature, pressure and exhaust gas
      composition has been made. Ash samples were collected at several locations along
      the furnace and flue gas treatment devices (cyclone and bag filter) after each
      combustion experiment and were analysed for their unburnt carbon content and
      chemical composition. Total suspended particles (TSP) in the combustion flue gas
      were evaluated at the inlet and outlet of cyclone and baghouse filter and further
      analysed for organic and elemental carbon, carbonates and 57 chemical elements.
      High particulate matter collection efficiencies in the range of 94-99% were
      observed for the baghouse, while removal rates of only 1.4-17% were registered
      for the cyclone. Due to the sand bed, Si was the major element in bottom ashes.
      Fly ashes, in particular those from eucalypt combustion, were especially rich in
      CaO, followed by relevant amounts of SiO2, MgO and K2O. Ash characteristics
      varied among experiments, showing that their inorganic composition strongly
      depends on both the biomass composition and combustion conditions. Inorganic
      constituents accounted for TSP mass fractions up to 40 wt%. Elemental carbon,
      organic matter and carbonates contributed to TSP mass fractions in the ranges
      0.58-44%, 0.79-78% and 0.01-1.7%, respectively.

PMID- 27889887
TI  - Heavy metals in five Sabellidae species (Annelida, Polychaeta): ecological
      implications.
AB  - The present work analyzed three hard-bottom and two soft-bottom species of
      sabellid polychaetes to determine the content of several heavy metals in their
      branchial crown and body. The highest concentrations of heavy metals were
      recorded in the hard-bottom species Branchiomma bairdi, a recent Mediterranean
      introduction. Differences in the metal concentrations were most notable in the
      high trace metal levels of the branchial crown for all the studied species.
      Statistical analysis showed that the Mediterranean hard-bottom species were
      similar each other in their heavy metal content in the body as well as in the
      branchial crown and appeared separated from all the other species. Arsenic and
      vanadium hyperaccumulation in the branchial crowns of the considered sabellid
      species probably acts as a deterrent for predation. The observed differences
      among the examined species were discussed not only at the light of habitat
      colonization but also in terms of the phylogeny.

PMID- 27889889
TI  - Biosurfactant production by the crude oil degrading Stenotrophomonas sp. B-2:
      chemical characterization, biological activities and environmental applications.
AB  - In this work, biosurfactant-producing microorganisms were isolated from
      hydrocarbon-contaminated water collected from Tunisian oilfield. After enrichment
      and isolation, different bacterial strains were preliminary studied for their
      biosurfactant/bioemulsifier properties when using crude oil as the unique carbon
      source. In particular, the isolate strain B-2, a Gram-negative, rod-shaped
      bacterium, efficiently emulsified crude oil. The extracellular biosurfactant
      product from this strain presented an emulsification activity above 70% and a
      hydrophobicity of 71%. In addition, a diameter of 6 cm was observed in the oil
      displacement test. The characterization of B-2 strain using 16S rDNA sequencing
      enables us to find a high degree of similarity with various members of the genus
      Stenotrophomonas (with a percentage of similarity of 99%). The emulsification
      activity of Stenotrophomonas biosurfactant B-2 was maintained in a wide range of
      pH (2 to 6), temperature (4 to 55  degrees C), and salinity (0 to 50 g L-1)
      conditions. It also enhanced the solubility of phenanthrene in water and could be
      used in the re-mobilization of hydrocarbon-contaminated environment. In addition,
      this biosurfactant exhibited antimicrobial and antioxidant properties. Infrared
      spectroscopy suggested potential lipidic and peptidic moieties, and mass
      spectrometry-based analyses showed that the biosurfactant contains mainly cyclic
      peptidic structures belonging to the class of diketopiperazines. Therefore, the B
      2 strain is a promising biosurfactant-producing microorganism and its derived
      biosurfactant presents a wide range of industrial applications.

PMID- 27889892
TI  - Effects of Mental Stress Induction on Heart Rate Variability in Patients with
      Panic Disorder.
AB  - Reduced heart rate variability (HRV) constitutes a widely used marker of cardiac
      autonomic inflexibility which has been linked to disorders such as panic disorder
      (PD). To date, the pathophysiological mechanisms whereby panic leads to
      attenuated HRV are not fully elucidated. We aimed to investigate the hypothesis
      that PD patients show pathological reactivity both in response to interoceptive
      and psychosocial stress in comparison to healthy individuals. We performed a
      controlled study on 38 patients diagnosed with PD [20 males and 18 females aged
      35.55 +/- 10.12 years, mean +/- standard deviation] and 23 age and gender matched
      healthy control participants. Distress was induced using the Trier Social Stress
      Test (TSST) and the dexamethasone-corticotropin-releasing-hormone (DEX-CRH) test.
      We assessed HRV prior to, during, and post-stress induction using the root mean
      square successive differences (RMSSD) as well as spectral analysis (high
      frequency; HF and low frequency; LF). Statistical analyses revealed significant
      main effects of time for mean heart rate (HR), HF, LF (solely DEX-CRH), LFHF
      ratio (solely TSST) and the RMSSD. Significant interaction effects were observed
      with more pronounced increases in mean HR (TSST) and LFHF-ratio (DEX-CRH) in the
      healthy control participants. No significant main effects of group were observed.
      Overall, our results indicate "normal" HRV parameters in patients with PD. The
      HRV of PD patients is no worse than that of healthy control participants since
      the HRV profiles were similar between the study groups. The current study is one
      of rather rarely published studies which was unable to show an influence of PD on
      HRV. Implications for future studies are under discussion.

PMID- 27889890
TI  - Protective role of quercetin against hematotoxic and immunotoxic effects of furan
      in rats.
AB  - Furan (Fu) is a liver carcinogen produced during heating process of food and
      concerns a public health problem. The current study was undertaken to evaluate
      the protective role of quercetin (Que) on Fu-induced hematological,
      immunological, and histopathological alterations in rats. Fifty male Sprague
      Dawley rats were divided into five equal groups. Group I (Cont) received
      distilled water, group II (CO) received corn oil, group III (Que) received Que at
      50 mg/kg BW, group IV (Fu) received Fu at 16 mg/kg BW, and group V received Que +
      Fu simultaneously; all groups gavaged daily for 30 days. Our results revealed
      that Fu administration significantly elevated RBCs, Hb, PCV, WBCs, lymphocytes,
      and granulocytes and reduced phagocytic percent (Ph%) and index (PhI). Fu
      decreased the serum total protein, albumin, globulin, IgM, IgG, and IL4, with a
      significant increase in the TNFalpha and 8-OHdG. Moreover, it decreased the GSH
      content and GST activity and increased the MDA levels in the splenic tissue.
      Histopathologically, Fu led to a moderate depletion in the lymphoid cells and
      weak immunostaining of CD20 antigen of few lymphocytes appeared in the spleen.
      Meanwhile, Que co-administration ameliorated the altered hematological parameters
      and improved the Ph% and PhI. It modulated the serum biochemical parameters and
      immunoglobulins. Moreover, it decreased lipid peroxidation and enhanced
      antioxidant status in the spleen. The results indicated that Que possesses
      antioxidant protective activity against Fu-induced oxidative damage and
      stimulates the immune function.

PMID- 27889893
TI  - Monitoring and distribution patterns of pesticide residues in soil from
      cotton/wheat fields of Pakistan.
AB  - The excessive use of hazardous pesticides for massive cotton and wheat production
      has deteriorated the quality of Okara district's soil. Thus, in order to sustain
      the production of good-quality food, it is essential to determine the residue
      levels of pesticides in the agricultural soil and define their possible sources.
      Thus, the present study focused on the determination of selected pesticides in
      the soil samples obtained from cotton/wheat fields by using the modified multi
      residue pesticide analysis method based on GCMS and HPLC-UV. Most of soil samples
      were found to be highly contaminated with imidacloprid, chlorpyrifos, and alpha
      cypermethrin residues. Selected pesticides were significantly correlated with
      each other at p < 0.05 except imidacloprid, which was negatively correlated with
      triazophos, MCPA methyl ester, selected pyrethroid pesticides, and their
      metabolite. Soil pH and phosphate levels were significantly positively correlated
      while sulfate content was negatively correlated with most of selected pesticides.
      The varimax normalized factor analysis divides the selected pesticides to the two
      major factors that explained 87.19% of the total variance which evidenced that
      pesticide in the same cluster shared a common source in the soil. A significant
      negative correlation of chlorpyrifos in the second factor pointed towards a
      source different from other pesticides. Factor and cluster analysis indicated
      that sulfate levels of soil positively affected the persistence/ mobility of
      imidacloprid.

PMID- 27889894
TI  - Glucocorticoid-Induced Leucine Zipper in Central Nervous System Health and
      Disease.
AB  - The central nervous system (CNS) is a large network of intercommunicating cells
      that function to maintain tissue health and homeostasis. Considerable evidence
      suggests that glucocorticoids exert both neuroprotective and neurodegenerative
      effects on the CNS. Glucocorticoids act by binding two related receptors in the
      cytoplasm, the mineralocorticoid receptor (MR) and the glucocorticoid receptor
      (GR). The glucocorticoid receptor complex mediates cellular responses by
      transactivating target genes and by protein: protein interactions. The
      paradoxical effects of glucocorticoids on neuronal survival and death have been
      attributed to the concentration and the ratio of mineralocorticoid to
      glucocorticoid receptor activation. Glucocorticoid-induced leucine zipper (GILZ)
      is a recently identified protein transcriptionally upregulated by
      glucocorticoids. Constitutively, expressed in many tissues including brain, GILZ
      mediates many of the actions of glucocorticoids. It mimics the anti-inflammatory
      and anti-proliferative effects of glucocorticoids but exerts differential effects
      on stem cell differentiation and lineage development. Recent experimental data on
      the effects of GILZ following induced stress or trauma suggest potential roles in
      CNS diseases. Here, we provide a short overview of the role of GILZ in CNS health
      and discuss three potential rationales for the role of GILZ in Alzheimer's
      disease pathogenesis.

PMID- 27889897
TI  - Growth Differentiation Factor 15 Is a Novel Diagnostic Biomarker of Mitochondrial
      Diseases.
AB  - The present study aimed to investigate whether serum growth differentiation
      factor 15 concentration is a valuable and reliable diagnostic biomarker of
      mitochondrial diseases. We examined consecutive patients with mitochondrial
      diseases, in comparison with patients with non-mitochondrial disease
      neuromuscular disorders and healthy controls. The serum concentrations of growth
      differentiation factor 15 were measured by ELISA, and compared with those of
      FGF21, lactate, and creatine kinase. We also evaluated the correlations between
      growth differentiation factor 15 concentrations and the Newcastle Mitochondrial
      Disease Adult Scale, numbers of ragged-red fibers, and COX-negative fibers in the
      biopsied muscles. The median serum growth differentiation factor 15 concentration
      was significantly elevated in 42 patients with mitochondrial diseases, compared
      with 20 patients with non-mitochondrial disease neuromuscular disorders and 50
      healthy controls. The area under the curve of growth differentiation factor 15
      for the diagnosis of muscle-manifesting mitochondrial diseases was 0.999, in
      comparison with those area under the curves of the other biomarkers including
      fibroblast growth factor 21 (0.935, p < 0.01), lactate (0.845 for p < 0.001), and
      creatine kinase (0.575, p < 0.001). Growth differentiation factor 15 was
      significantly correlated with mitochondrial disease severity and the proportion
      of ragged-red fibers identified in the biopsied muscles. Circulating growth
      differentiation factor 15 measurement is a superior biomarker with high
      sensitivity and specificity, which can be used as a non-invasive test to screen
      for primary mitochondrial diseases and dysmetabolic myopathy with associated
      mitochondrial dysfunction in susceptible individuals.

PMID- 27889895
TI  - Inflammatory Response in the CNS: Friend or Foe?
AB  - Inflammatory reactions could be both beneficial and detrimental to the brain,
      depending on strengths of their activation in various stages of
      neurodegeneration. Mild activation of microglia and astrocytes usually reveals
      neuroprotective effects and ameliorates early symptoms of neurodegeneration; for
      instance, released cytokines help maintain synaptic plasticity and modulate
      neuronal excitability, and stimulated toll-like receptors (TLRs) promote
      neurogenesis and neurite outgrowth. However, strong activation of glial cells
      gives rise to cytokine overexpression/dysregulation, which accelerates
      neurodegeneration. Altered mutual regulation of p53 protein, a major tumor
      suppressor, and NF-kappaB, the major regulator of inflammation, seems to be
      crucial for the shift from beneficial to detrimental effects of neuroinflammatory
      reactions in neurodegeneration. Therapeutic intervention in the p53-NF-kappaB
      axis and modulation of TLR activity are future challenges to cope with
      neurodegeneration.

PMID- 27889896
TI  - Decreased Anxiety-Related Behaviour but Apparently Unperturbed NUMB Function in
      Ligand of NUMB Protein-X (LNX) 1/2 Double Knockout Mice.
AB  - NUMB is a key regulator of neurogenesis and neuronal differentiation that can be
      ubiquitinated and targeted for proteasomal degradation by ligand of numb protein
      X (LNX) family E3 ubiquitin ligases. However, our understanding of LNX protein
      function in vivo is very limited. To examine the role of LNX proteins in
      regulating NUMB function in vivo, we generated mice lacking both LNX1 and LNX2
      expression in the brain. Surprisingly, these mice are healthy, exhibit unaltered
      levels of NUMB protein and do not display any neuroanatomical defects indicative
      of aberrant NUMB function. Behavioural analysis of LNX1/LNX2 double knockout mice
      revealed decreased anxiety-related behaviour, as assessed in the open field and
      elevated plus maze paradigms. By contrast, no major defects in learning, motor or
      sensory function were observed. Given the apparent absence of major NUMB
      dysfunction in LNX null animals, we performed a proteomic analysis to identify
      neuronal LNX-interacting proteins other than NUMB that might contribute to the
      anxiolytic phenotype observed. We identified and/or confirmed interactions of
      LNX1 and LNX2 with proteins known to have presynaptic and neuronal signalling
      functions, including the presynaptic active zone constituents ERC1, ERC2 and
      LIPRIN-alphas (PPFIA1, PPFIA3), as well as the F-BAR domain proteins FCHSD2
      (nervous wreck homologue) and SRGAP2. These and other novel LNX-interacting
      proteins identified are promising candidates to mediate LNX functions in the
      central nervous system, including their role in modulating anxiety-related
      behaviour.

PMID- 27889900
TI  - Unbearable Pruritus After Withdrawal of (Levo)cetirizine.
AB  - Twelve cases of unbearable pruritus several days after withdrawal of
      (levo)cetirizine were reported to the Netherlands Pharmacovigilance Centre Lareb.
      Eleven reports concerned women and one report concerned a man, aged 19-58 years.
      These patients had been using these antihistamines continuously for months or
      years. They had tried to stop using antihistamines on several occasions but felt
      unable to withdraw the drug because of the unbearable maddening itch. Finally,
      slowly tapering the drug or using a short course of corticosteroids helped to
      withdraw (levo)cetirizine. The Naranjo assessment score ranged from two to four
      for all the cases, indicating a possible relationship.

PMID- 27889898
TI  - The Transcription Factors EBF1 and EBF2 Are Positive Regulators of Myelination in
      Schwann Cells.
AB  - Myelin formation by Schwann cells is tightly controlled by multiple pathways and
      regulatory molecules. The Ebf2 gene, belonging to the Ebf family of transcription
      factors regulating cell development and differentiation, is expressed in Schwann
      cells, and Ebf2 knockout mice show peripheral nerve defects. We also found that
      Ebf1 is expressed in Schwann cells. To investigate Ebf function in myelination,
      we silenced Ebf genes in myelinating dorsal root ganglia cultures. Combined
      downregulation of Ebf genes leads to a severe impairment of myelin formation that
      is completely rescued by their specific overexpression, suggesting that the
      expression level of Ebf genes strongly influences axon myelination. In addition,
      by profiling Ebf target genes, we found several transcripts belonging to pathways
      actively involved in peripheral myelination, including Gliomedin, a gene with a
      role in the formation of the nodes of Ranvier and recently implicated in the
      pathogenesis of the nodo-paranodopathies. Our results suggest that Ebf genes act
      as positive regulators of myelination and directly regulate the promoter of
      Gliomedin.

PMID- 27889901
TI  - A novel approach to screening for familial hypercholesterolemia in a large public
      venue.
AB  - The primary aim of this study was to test the feasibility of a public health
      screening program to identify individuals at high risk of familial
      hypercholesterolemia through a novel screening approach at a large public venue.
      A finger-prick, non-fasting lipid panel was obtained, and a survey which
      consisted of 44 open- and close-ended questions divided into four sections:
      medical and family history of FH, opinions of cascade genetic testing, patient
      activation, and demographics was completed. A total of 971 participants met
      criteria and completed a cholesterol screen. In total, five individuals met
      either the Simon Broome Register or the Dutch Lipid Clinic Network criteria for
      possible familial hypercholesterolemia. Participants were generally positive
      towards genetic testing, and the vast majority listed they had no barriers to
      communication of genetic testing information to family members. However, the most
      common barrier listed was lack of communication skills. Our results suggest that
      a public health screening program for FH is viable at a large public venue. We
      argue that further research is needed to expand this study to a fully operational
      screening program.

PMID- 27889903
TI  - A case report: hemothorax caused by rupture of the left atrial appendage.
AB  - Cardiac rupture is defined as a full-thickness myocardial tear; this injury after
      blunt chest trauma is rare, and is associated with high mortality. Blunt cardiac
      rupture typically presents with either cardiac tamponade or massive hemothorax,
      and is often unrecognized in the context of blunt chest trauma. It is a little
      known fact that pericardial effusions can decrease due to pericardial
      lacerations. Hence, cardiac rupture with pericardial lacerations may be easily
      overlooked especially by chest surgeons. We herein report a case of hemothorax
      caused by rupture of the left atrial appendage. An 80-year-old male was involved
      in a motor vehicle crash. We made the diagnosis of hemothorax on the basis of
      bloody thoracic effusion and left pleural effusion on computed tomography (CT).
      CT also showed small pericardial effusion in amount and non-displaced rib
      fractures. We made a tentative diagnosis of intercostal artery injury with rib
      fractures, we performed left thoracotomy. However, in the operating room, we
      recognized that cardiac rupture led to massive hemothorax, and that hemothorax
      was not associated with intercostal artery injury. We repaired left atrial
      appendage rupture, and his postoperative course was uneventful. Cardiac rupture
      can present as slight pericardial effusion with hemothorax. On the basis of this
      case, we propose that cardiac rupture should be considered at the time of
      hemothorax examination with careful attention to pericardial effusions.

PMID- 27889899
TI  - A1 Adenosine Receptor Activation Modulates Central Nervous System Development and
      Repair.
AB  - Adenosine is an endogenous, autacoid purine nucleoside which performs many
      important biological roles, particularly during stressful events. Adenosine can
      signal through four adenosine receptor (AR) subtypes: A1, A2A, A2B, and A3. Of
      these, adenosine A1 receptor (A1AR) has a broad, wide distribution throughout
      different vertebrate cell types and the highest affinity to adenosine. The A1AR
      dependent action of adenosine is well documented in reports from numerous studies
      that have used different selective A1AR agonists and antagonists as well as in
      animals that have a genetically manipulated A1AR gene. Despite its wide
      distribution and function, A1AR homo/hetero-oligomerization with other adenosine
      and non-adenosine receptors extends its biological role during developmental,
      physiological, and pathological situations. In this review, we initially discuss
      the A1AR structure and most important signaling pathway triggered by its
      activation. Next, we summarize some of the most well-known biological effects of
      A1AR in the central nervous system (CNS) during development and adulthood, in
      addition to its role in nervous system regeneration and repair.

PMID- 27889902
TI  - Establishment and characterization of a novel uterine carcinosarcoma cell line,
      TU-ECS-1, with mutations of TP53 and KRAS.
AB  - A new human uterine carcinosarcoma (UCS) cell line, TU-ECS-1, was established and
      characterized. The morphological appearance of the cultured cells was an insular
      of epithelial-like cells arranged in the form of a jigsaw puzzle and mesenchymal
      like cells with a spindle-shaped or fibroblast-like morphology. A relatively high
      proliferation rate was observed with a doubling time of 18.2 h. The chromosome
      number ranged from 44 to 49 and had an extra chromosome 12 (trisomy 12). The
      respective half-maximal inhibitory concentrations of cisplatin, paclitaxel, and
      doxorubicin were 2.9 uM, 154 nM, and 219 ng/mL, respectively. Mutational analysis
      revealed that TU-ECS-1 cells have mutations of TP53 in exons 4, 6, and 8 and of
      KRAS at codon 12 (G12D) in exon 2, which is a mutation hot spot on this gene.
      Western blot analysis showed that p53 protein was overexpressed in TU-ECS-1
      cells. Immunostaining of the cultured cells and in vivo tumors showed that the TU
      ECS-1 cells and xenografts were positive for epithelial marker cytokeratin AE1/3
      and mesenchymal marker vimentin. These results suggested that TU-ECS-1 cells
      might have both epithelial and mesenchymal characteristics. This cell line may be
      useful to study the carcinogenesis of UCS and contribute to the development of
      novel treatment strategies.

PMID- 27889904
TI  - How to Screen for Non-Adherence to Antihypertensive Therapy.
AB  - The quality of assessment of non-adherence to treatment in hypertensive is poor.
      Within this review, we discuss the different methods used to assess adherence to
      blood-pressure-lowering medications in hypertension patients. Subjective reports
      such as physicians' perceptions are inaccurate, and questionnaires completed by
      patients tend to overreport adherence and show a low diagnostic specificity.
      Indirect objective methods such as pharmacy database records can be useful, but
      they are limited by the robustness of the recorded data. Electronic medication
      monitoring devices are accurate but usually track adherence to only a single
      medication and can be expensive. Overall, the fundamental issue with indirect
      objective measures is that they do not fully confirm ingestion of
      antihypertensive medications. Detection of antihypertensive medications in body
      fluids using liquid chromatography-tandem mass spectrometry is currently, in our
      view, the most robust and clinically useful method to assess non-adherence to
      blood-pressure-lowering treatment. It is particularly helpful in patients
      presenting with resistant, refractory or uncontrolled hypertension despite the
      optimal therapy. We recommend using this diagnostic strategy to detect non
      adherence alongside a no-blame approach tailoring support to address the
      perceptions (e.g. beliefs about the illness and treatment) and practicalities
      (e.g. capability and resources) influencing motivation and ability to adhere.

PMID- 27889905
TI  - Ligand binding and conformational dynamics in a flavin-based electron-bifurcating
      enzyme complex revealed by Hydrogen-Deuterium Exchange Mass Spectrometry.
AB  - Flavin-based electron bifurcation (FBEB) is a novel mechanism of energy coupling
      used by anaerobic microorganisms to optimize their energy metabolism efficiency.
      The first high-resolution structure of a complete FBEB enzyme complex, the NADH
      dependent reduced ferredoxin: NADP+ -oxidoreductase (NfnAB) of Thermotoga
      maritima, was recently solved. However, no experimental evidence for the NADPH
      binding site and conformational changes during the FBEB reaction are available.
      Here we analyzed ligand binding and the conformational dynamics of oxygen
      sensitive NfnAB using Hydrogen-Deuterium Exchange Mass-Spectrometry, including a
      customized anaerobic workflow. We confirmed the NADH and the previously
      postulated NADPH-binding site. Furthermore, we observed an NfnA-NfnB
      rearrangement upon NADPH binding which supports the proposed FBEB mechanism.

PMID- 27889906
TI  - Interventions for the Management of Denture Stomatitis: A Systematic Review and
      Meta-Analysis.
AB  - OBJECTIVES: To assess the effectiveness of different interventions for treating
      or preventing denture stomatitis (DS). DESIGN: Systematic review. SETTING:
      Randomized controlled trials (RCTs) comparing any agent or procedure prescribed
      to treat or prevent DS in adults. PARTICIPANTS: Older adults with denture
      stomatitis. MEASUREMENTS: There were two main outcomes reported in the trials
      included in this review: clinical signs of DS and remaining presence of yeast.
      There were no restrictions regarding language or date of publication. The search
      period was up to February 2016. RESULTS: Thirty-five studies were included in the
      systematic review, with 32 judged as having high risk of bias. Three RCTs
      compared nystatin with placebo and found a significant effect on the reduction of
      clinical signs of stomatitis (risk ratio (RR) = 0.51, 95% confidence interval
      (CI) = 0.36-0.72), four RCTs compared nystatin with placebo and found a
      significant effect on mycological assessment (RR = 0.61, 95% CI = 0.46-0.80).
      Five studies of disinfectant agents also showed a significant effect in
      comparison with an inactive agent (RR = 0.52, 95% CI = 0.30-0.92) in clinical
      assessment. No evidence was found of an effect of miconazole, amphotericin, or
      imidazolic drugs. No RCT evaluated the effectiveness of preventive approaches.
      CONCLUSION: The results are supportive of the use of nystatin and disinfecting
      agents in the treatment of DS, but clinicians need to be aware that individual
      studies had high risk of bias and that the overall quality of the individual
      reports was judged to be low.

PMID- 27889909
TI  - Our Hidden Patients.

PMID- 27889907
TI  - Activation of Nur77 in microglia attenuates proinflammatory mediators production
      and protects dopaminergic neurons from inflammation-induced cell death.
AB  - Microglia-mediated neuroinflammation plays a critical role in the pathological
      development of Parkinson's disease (PD). Orphan nuclear receptor Nur77 (Nur77) is
      abundant in neurons, while its role in microglia-mediated neuroinflammation
      remains unclear. The present data demonstrated that the expression of Nur77 in
      microglia was reduced accompanied by microglia activation in response to
      lipopolysaccharide (LPS) in vitro and in experimental 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-PD mouse model. Nur77 over-expression or application of Nur77
      agonist cytosporone B suppressed the expression of proinflammatory genes, such as
      inducible nitric oxide NOS, cyclooxygenase-2, IL-1beta, and tumor necrosis factor
      alpha in the activated microglia, while silenced Nur77 exaggerated the
      inflammatory responses in microglia. Moreover, activation of Nur77 suppressed the
      LPS-induced NF-kappaB activation which was partly dependent on p38 MAPK activity,
      since inhibition of p38 MAPK by SB203580 abolished the LPS-activated NF-kappaB in
      microglia. On the other hand, inhibition of p38 MAPK attenuated LPS-induced Nur77
      reduction. Furthermore, in a microglia-conditioned cultured media system, Nur77
      ameliorated the cytotoxicity to MN9D dopaminergic cells. Lastly, cytosporone B
      attenuated microglia activation and loss of dopaminergic neuron in the substantia
      nigra pars compacta (SNpc) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-PD
      mouse model. Taken together, these findings revealed the first evidence that
      Nur77 was an important modulator in microglia function that associated with
      microglia-mediated dopaminergic neurotoxicity, and thus modulation of Nur77 may
      represent a potential novel target for treatment for neurodegenerative disease.

PMID- 27889910
TI  - Elimination of the apposition in Latin anatomical terms.
AB  - The anatomical nomenclature rules require that terms be as short and simple as
      possible. One common exception to that rule is Latin terms that contain two nouns
      in nominative case, for example, Musculus masseter and Os ischium. Although these
      may appear to speakers of other languages to be compound nouns, they are
      appositions, grammatical structures in which one noun renames, defines or
      describes the entity named by the other noun. More than 125 terms in Terminologia
      Anatomica can be simplified, without loss of clarity, by prohibiting use of more
      than one noun in nominative case in Latin anatomical terms (e.g., Masseter and Os
      ischii). Clin. Anat. 30:156-158, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27889908
TI  - Self-Reported Masticatory Dysfunction and Mortality in Community Dwelling Elderly
      Adults: A 9-Year Follow-Up.
AB  - OBJECTIVES: To evaluate the association, if any, between masticatory dysfunction
      (MD) and mortality in older adults. DESIGN: The Invecchiare in Chianti
      (InCHIANTI) Study, a cohort study with 9-year follow-up. SETTING: Tuscany, Italy.
      PARTICIPANTS: Individuals aged 65 and older (N = 1,155). MEASUREMENTS: MD was
      self-reported; Cox regression was used to assess the association between self
      reported MD and 9-year all-cause mortality. This association was also evaluated
      after stratifying according to use of dentures. Analyses were adjusted for
      potential confounders, including demographic characteristics, lifestyle habits,
      comorbidities, nutrient intake, medications, and objective parameters. RESULTS:
      Four hundred five (35%) participants reported MD. Over the 9-year follow-up, 475
      (41%) subjects died. According to Cox regression analysis, self-reported MD was
      associated with higher mortality (relative risk (RR) = 1.23, 95% confidence
      interval (CI) = 1.02-1.48), after adjusting for potential confounders. In
      participants with self-reported MD, uncorrected edentulism was the condition
      associated with the greatest risk of mortality (RR = 2.10, 95% CI = 1.07-4.14);
      use of dentures seemed to blunt this association (RR = 1.12, 95% CI = 0.87-1.44).
      CONCLUSION: Self-reported MD, chiefly when due to uncorrected edentulism, is
      associated with 9-year all-cause mortality in community-dwelling elderly adults.
      Further studies are needed to evaluate whether the timely correction of MD using
      adequate dentures can increase the survival of older adults.

PMID- 27889912
TI  - Insulin-like growth factor 1 and metabolic parameters are associated with
      nonalcoholic fatty liver disease in obese children and adolescents.
AB  - AIM: Few studies have investigated the relationship between paediatric
      nonalcoholic fatty liver disease (NAFLD) and insulin-like growth factor 1 (IGF
      1). This study, carried out from July 2013 to September 2015, aimed to fill the
      gap and added metabolic parameters to the analysis. METHODS: This was a cross
      sectional study of 168 obese children and adolescents (84% male), divided into
      two groups based on the presence (n = 90) or absence (n = 78) of NAFLD. All
      participants underwent clinical examinations, anthropometric and laboratory
      examinations and liver ultrasonography. RESULTS: Nonalcoholic fatty liver disease
      patients had significantly lower IGF-1 standard deviation score (IGF-1 SDS) and
      higher body mass index (BMI), homeostasis model assessment of insulin resistance
      (HOMA-IR) and uric acid levels than the control group. The prevalence rate of
      NAFLD was negatively correlated with the IGF-1 SDS. IGF-1 SDS was negatively
      associated with NAFLD, while BMI, HOMA-IR and uric acid were positively
      associated with NAFLD. The combined analysis of the area under the receiver
      operating characteristic curve for multiple variables, including IGF-1 SDS, BMI,
      HOMA-IR and uric acid, was 0.812, with a sensitivity of 78.89% and specificity of
      74.36%. CONCLUSION: IGF-1, BMI, HOMA-IR and uric acid were useful markers of
      NAFLD in obese children and adolescents.

PMID- 27889911
TI  - Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine
      throughout the progression of Alzheimer's disease.
AB  - Epigenetic modifications to cytosine are known to alter transcriptional states
      and deregulate gene expression in cancer, embryonic development, and most
      recently in neurodegeneration. To test the hypothesis that global levels of
      cytosine modification are altered throughout the progression of Alzheimer's
      disease, 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) were
      quantified using gas chromatography/mass spectrometry (GC/MS) and stable labeled
      internal standards of cytosine, 5-mC, and 5-hmC. Cytosine modifications were
      quantified in DNA extracted from tissue specimens of four brain regions
      (cerebellum, inferior parietal lobe, superior and middle temporal gyrus, and
      hippocampus/parahippocampal gyrus) of cognitively normal control (NC) subjects
      and subjects with mild cognitive impairment (MCI), preclinical Alzheimer's
      disease (PCAD), late onset Alzheimer's disease, frontotemporal lobar degeneration
      (FTLD) and dementia with Lewy bodies (DLB). Repeated measures analyses of the
      data show significant alterations in 5-mC and 5-hmC in early stages of
      Alzheimer's disease (PCAD and MCI), as well as FTLD and DLB subjects, across
      multiple regions of the brain. These data suggest alterations in epigenetic
      regulation of genes may play an early role in the progression of AD as well as
      other types of neurodegeneration.

PMID- 27889914
TI  - Predictors of Long-Term Mortality in Older Patients Hospitalized for Acutely
      Decompensated Heart Failure: Clinical Relevance of Natriuretic Peptides.
AB  - BACKGROUND: Acute heart failure is a common cause of hospitalization among older
      patients. Optimized risk stratification might improve the outcome for this
      subgroup of patients. Natriuretic peptides have been used in the diagnosis of
      heart failure and in evaluating the prognosis of patients hospitalized for heart
      failure. However, their utility in the elderly is still controversial. OBJECTIVE:
      To evaluate long-term survival and prognostic factors for elderly patients
      hospitalized for acutely decompensated heart failure and evaluate the prognostic
      utility of NT-proBNP. DESIGN: Retrospective, multicenter cohort study. SETTING:
      Two Italian hospitals. PARTICIPANTS: Two hundred seventy-nine patients, aged >75
      years; hospitalized for decompensation of chronic, established heart failure.
      METHODS: Baseline clinical data were recorded at admission. The primary outcome
      was long-term mortality. RESULTS: In-hospital, 12-month and 5-year mortality
      were, respectively, 10%, 36%, and 77%. NT-proBNP, eGFR, hemoglobin, diabetes,
      systolic blood pressure, and moderate to severe tricuspid regurgitation were
      independently associated with long-term prognosis and were entered into a
      multivariate model, with a C-index of 0.765 for the determination of high-risk
      patients. The C-index for NT-proBNP to predict mortality at 2 and 12 months was
      0.740 and 0.756, respectively. The optimal cutoff point for predicting mortality
      at 2 and 12 months was 8,444 pg/mL (hazard ratio 5.33) and 8,275 pg/mL (hazard
      ratio 6.03), respectively. CONCLUSION: Elderly patients hospitalized for acutely
      decompensated heart failure had a poor long-term outcome, especially in the
      subgroup with reduced ejection fraction (EF). In addition to EF and
      comorbidities, NT-pro-BNP remained independently prognostic among elderly
      patients hospitalized with heart failure.

PMID- 27889913
TI  - Long-term melatonin treatment delays ovarian aging.
AB  - Ovarian aging is characterized by gradual declines in oocyte quantity and
      quality. Melatonin is considered an anti-aging agent due to its cytoprotective
      actions as an antioxidant. This study examined whether long-term melatonin
      treatment would delay ovarian aging in mice. Female ICR mice (10 weeks old) were
      given melatonin-containing water (100 MUg/mL; melatonin) or water only until 43
      weeks of age. Their oocytes were recovered from the oviduct, and in vitro
      fertilization was performed. The ovaries were used for a histological analysis of
      the number of follicles. The mRNA expression of the aging-related sirtuin genes
      (SIRT1, SIRT3) and the autophagy-related gene (LC3) and the telomere length of
      the ovarian chromosomes were analyzed. Transcriptome changes in the ovaries were
      also characterized using microarray. The number of ovulated oocytes decreased
      with age; however, it was greater in melatonin-treated mice than that from
      control animals. The decreased fertilization rate and blastocyst rate during
      aging also were higher in the melatonin-treated mice than in the controls, as
      were the numbers of primordial, primary, and antral follicles. The mRNA
      expression of SIRT1 and LC3 and telomere length were enhanced due to melatonin
      treatment. Seventy-eight genes that were downregulated during aging and
      upregulated by melatonin were identified by a microarray analysis. Forty of these
      78 genes were ribosome-related genes, and a free radical scavenging network was
      identified. The present results indicate that melatonin delays ovarian aging by
      multiple mechanisms including antioxidant action, maintaining telomeres,
      stimulating SIRT expression and ribosome function, and by reducing autophagy.

PMID- 27889916
TI  - Precipitation alters interactions in a grassland ecological community.
AB  - Climate change is transforming precipitation regimes world-wide. Changes in
      precipitation regimes are known to have powerful effects on plant productivity,
      but the consequences of these shifts for the dynamics of ecological communities
      are poorly understood. This knowledge gap hinders our ability to anticipate and
      mitigate the impacts of climate change on biodiversity. Precipitation may affect
      fauna through direct effects on physiology, behaviour or demography, through
      plant-mediated indirect effects, or by modifying interactions among species. In
      this paper, we examined the response of a semi-arid ecological community to a
      fivefold change in precipitation over 7 years. We examined the effects of
      precipitation on the dynamics of a grassland ecosystem in central California from
      2007 to 2013. We conducted vegetation surveys, pitfall trapping of invertebrates,
      visual surveys of lizards and capture-mark-recapture surveys of rodents on 30
      plots each year. We used structural equation modelling to evaluate the direct,
      indirect and modifying effects of precipitation on plants, ants, beetles,
      orthopterans, kangaroo rats, ground squirrels and lizards. We found pervasive
      effects of precipitation on the ecological community. Although precipitation
      increased plant biomass, direct effects on fauna were often stronger than plant
      mediated effects. In addition, precipitation altered the sign or strength of
      consumer-resource and facilitative interactions among the faunal community such
      that negative or neutral interactions became positive or vice versa with
      increasing precipitation. These findings indicate that precipitation influences
      ecological communities in multiple ways beyond its recognized effects on primary
      productivity. Stochastic variation in precipitation may weaken the average
      strength of biotic interactions over time, thereby increasing ecosystem stability
      and resilience to climate change.

PMID- 27889915
TI  - Constitutive regulation of the glutamate/aspartate transporter EAAT1 by Calcium
      Calmodulin-Dependent Protein Kinase II.
AB  - Glutamate clearance by astrocytes is an essential part of normal excitatory
      neurotransmission. Failure to adapt or maintain low levels of glutamate in the
      central nervous system is associated with multiple acute and chronic
      neurodegenerative diseases. The primary excitatory amino acid transporters in
      human astrocytes are EAAT1 and EAAT2 (GLAST and GLT-1, respectively, in rodents).
      While the inhibition of calcium/calmodulin-dependent kinase (CaMKII), a
      ubiquitously expressed serine/threonine protein kinase, results in diminished
      glutamate uptake in cultured primary rodent astrocytes (Ashpole et al. 2013), the
      molecular mechanism underlying this regulation is unknown. Here, we use a
      heterologous expression model to explore CaMKII regulation of EAAT1 and EAAT2. In
      transiently transfected HEK293T cells, pharmacological inhibition of CaMKII
      (using KN-93 or tat-CN21) reduces [3 H]-glutamate uptake in EAAT1 without
      altering EAAT2-mediated glutamate uptake. While over-expressing the Thr287Asp
      mutant to enhance autonomous CaMKII activity had no effect on either EAAT1 or
      EAAT2-mediated glutamate uptake, over-expressing a dominant-negative version of
      CaMKII (Asp136Asn) diminished EAAT1 glutamate uptake. SPOTS peptide arrays and
      recombinant glutathione S-transferase-fusion proteins of the intracellular N- and
      C-termini of EAAT1 identified two potential phosphorylation sites at residues
      Thr26 and Thr37 in the N-terminus. Introducing an Ala (a non-phospho mimetic) at
      Thr37 diminished EAAT1-mediated glutamate uptake, suggesting that the
      phosphorylation state of this residue is important for constitutive EAAT1
      function. Our study is the first to identify a glutamate transporter as a direct
      CaMKII substrate and suggests that CaMKII signaling is a critical driver of
      constitutive glutamate uptake by EAAT1.

PMID- 27889917
TI  - The neuronal insulin receptor in its environment.
AB  - Insulin is known mainly for its effects in peripheral tissues, such as the liver,
      skeletal muscles and adipose tissue, where the activation of the insulin receptor
      (IR) has both short-term and long-term effects. Insulin and the IR are also
      present in the brain, and since there is evidence that neuronal insulin signaling
      regulates synaptic plasticity and that it is impaired in disease, this pathway
      might be the key to protection or reversal of symptoms, especially in Alzheimer's
      disease. However, there are controversies about the importance of the neuronal
      IR, partly because biophysical data on its activation and signaling are much less
      complete than for the peripheral IR. This review briefly summarizes the neuronal
      IR signaling in health and disease, and then focuses on known differences between
      the neuronal and peripheral IR with regard to alternative splicing and
      glycosylation, and lack of data with respect to phosphorylation and membrane
      subdomain localization. Particularities in the neuronal IR itself and its
      environment may have consequences for downstream signaling and impact synaptic
      plasticity. Furthermore, establishing the relative importance of insulin
      signaling through IR or through hybrids with its homolog, the insulin-like growth
      factor 1 receptor, is crucial for evaluating the consequences of brain IR
      activation. An improved biophysical understanding of the neuronal IR may help
      predict the consequences of insulin-targeted interventions.

PMID- 27889918
TI  - Inner ear labyrinth anatomy of monotremes and implications for mammalian inner
      ear evolution.
AB  - The monophyletic clade Monotremata branches early from the rest of the mammalian
      crown group in the Jurassic and members of this clade retain many ancestral
      mammalian traits. Thus, accurate and detailed anatomical descriptions of this
      group can offer unique insight into the early evolutionary history of Mammalia.
      In this study, we examine the inner ear anatomy of two extant monotremes,
      Ornithorhynchus anatinus and Tachyglossus aculeatus, with the primary goals of
      elucidating the ancestral mammalian ear morphology and resolving inconsistencies
      found within previous descriptive literature. We use histological serial sections
      and high-resolution microcomputed tomography (uCT) for correlating soft tissue
      features of the vestibule and cochlea to the osseous labyrinth endocast. We found
      that in both monotremes the scala tympani coils to a lesser degree than scala
      vestibuli and scala media, although all three scalae show an apical coil inside
      the osseous cochlear tube. The helicotrema (conduit between scala tympani and
      scala vestibuli) is in subapical position, and the cochlear and lagenar ganglia
      and their associated nerve fibers are not enclosed by bone. In comparison, in
      extant therian mammals (i.e., marsupials and placentals) the helicotrema is
      located at the apex of the osseous cochlear canal, the three scalae coil to the
      same degree and the cochlear ganglion is enclosed by the primary bony lamina.
      Whether the lagenar ganglion is lost in therian mammals or integrated into the
      cochlear ganglion is still debated. The presence of a sensory lagenar macula at
      the apex of the membranous cochlear duct, innervated by a separate lagenar nerve
      and ganglion is a plesiomorphic condition of amniotes that monotremes share. A
      separate osseous lagenar canaliculus for the lagenar nerve, and the coiling of
      the distended lagenar sac at the end of the cochlear duct are autapomorphies of
      monotremes. Based on our findings we hypothesize that the ancestral inner ear of
      stem mammaliaforms is characterized by a straight or slightly curved osseous
      cochlear canal, a lagenar macula, lagenar nerve fibers separated from a larger
      bundle of cochlear nerve fibers, the presence of an organ of Corti and an intra
      otic cochlear ganglion suspended by membranous connective tissue. Among the major
      Mesozoic clades of crown mammals, cladotherians and gondwanatherians most likely
      acquired a fully functioning organ of Corti but lost the sensory lagenar macula,
      like extant therians. However, Mesozoic spalacotherioids, multituberculates and
      eutriconodonts likely retained the mammaliaform condition. J. Morphol. 278:236
      263, 2017. (c) 2016 Wiley Periodicals,Inc.

PMID- 27889919
TI  - Human anatomy nomenclature rules for the computer age.
AB  - Information systems are increasing in importance in biomedical sciences and
      medical practice. The nomenclature rules of human anatomy were reviewed for
      adequacy with respect to modern needs. New rules are proposed here to ensure that
      each Latin term is uniquely associated with an anatomical entity, as short and
      simple as possible, and machine-interpretable. Observance of these
      recommendations will also benefit students and translators of the Latin terms
      into other languages. Clin. Anat. 30:300-302, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27889920
TI  - Neuropeptide Y receptor 1 is expressed by B and T lymphocytes and mast cells in
      infantile haemangiomas.
AB  - AIM: We investigated the expression of neuropeptide Y (NPY), NPY receptor 1
      (NPYR1) and NPY receptor 2 (NPYR2) in infantile haemangiomas (IHs). METHODS:
      Immunohistochemical (IHC) staining was performed on proliferating IHs from six
      patients aged 4-13 (mean 8.7) months and involuted IHs from six patients aged 5
      59 (mean 18.7) years, for the expression of NPY, NPYR1 and NPYR2. Protein and
      messenger ribonucleic acid expression corresponding to these proteins was
      investigated by Western blotting and NanoString analysis, respectively. RESULTS:
      IHC staining, Western blotting and NanoString analysis demonstrated the presence
      of NPYR1, but not NPYR2, within proliferating and involuted IHs. IHC staining
      showed NPYR1 was expressed by B and T lymphocytes expressing CD45 and mast cells
      expressing tryptase. IHC staining demonstrated the presence of NPY on the NPYR1+
      cells, but it was not detected by Western blotting or NanoString analysis.
      CONCLUSION: NPYR1, but not NPYR2, was present in IHs. The localisation of NPYR1
      to B and T lymphocytes and mast cells suggests its role in the biology of IHs.
      The demonstration of NPY on the NPYR1+ cells, without active transcription,
      suggests that NPY was not being produced within IHs.

PMID- 27889921
TI  - Chimpanzee uses manipulative gaze cues to conceal and reveal information to
      foraging competitor.
AB  - : Tactical deception has been widely reported in primates on a functional basis,
      but details of behavioral mechanisms are usually unspecified. We tested a pair of
      chimpanzees (Pan troglodytes) in the informed forager paradigm, in which the
      subordinate saw the location of hidden food and the dominant did not. We employed
      cross-correlations to examine temporal contingencies between chimpanzees'
      behavior: specifically how the direction of the subordinate's gaze and movement
      functioned to manipulate the dominant's searching behavior through two tactics,
      withholding, and misleading information. In Experiment 1, not only did the
      informed subordinate tend to stop walking toward a single high value food, but
      she also refrained from gazing toward it, thus, withholding potentially revealing
      cues from her searching competitor. In a second experiment, in which a moderate
      value food was hidden in addition to the high value food, whenever the
      subordinate alternated her gaze between the dominant and the moderate value food,
      she often paused walking for 5 s; this frequently recruited the dominant to the
      inferior food, functioning as a "decoy." The subordinate flexibly concealed and
      revealed gaze toward a goal, which suggests that not only can chimpanzees use
      visual cues to make predictions about behavior, but also that chimpanzees may
      understand that other individuals can exploit their gaze direction. These results
      substantiate descriptive reports of how chimpanzees use gaze to manipulate
      others, and to our knowledge are the first quantitative data to identify
      behavioral mechanisms of tactical deception. RESEARCH HIGHLIGHTS: Cross
      correlations show a subordinate chimpanzee tactically deceived a dominant by not
      gazing toward a valuable food (withholding), and recruiting to a "decoy" food
      (misleading). Chimpanzees understand that others can exploit their gaze
      direction.

PMID- 27889922
TI  - Haloperidol for long-term aggression in psychosis.
AB  - BACKGROUND: Psychotic disorders can lead some people to become agitated.
      Characterised by restlessness, excitability and irritability, this can result in
      verbal and physically aggressive behaviour - and both can be prolonged.
      Aggression within the psychiatric setting imposes a significant challenge to
      clinicians and risk to service users; it is a frequent cause for admission to
      inpatient facilities. If people continue to be aggressive it can lengthen
      hospitalisation. Haloperidol is used to treat people with long-term aggression.
      OBJECTIVES: To examine whether haloperidol alone, administered orally,
      intramuscularly or intravenously, is an effective treatment for long
      term/persistent aggression in psychosis. SEARCH METHODS: We searched the Cochrane
      Schizophrenia Group Trials Register (July 2011 and April 2015). SELECTION
      CRITERIA: We included randomised controlled trials (RCT) or double blind trials
      (implying randomisation) with useable data comparing haloperidol with another
      drug or placebo for people with psychosis and long-term/persistent aggression.
      DATA COLLECTION AND ANALYSIS: One review author (AK) extracted data. For
      dichotomous data, one review author (AK) calculated risk ratios (RR) and their
      95% confidence intervals (CI) on an intention-to-treat basis based on a fixed
      effect model. One review author (AK) assessed risk of bias for included studies
      and created a 'Summary of findings' table using GRADE. MAIN RESULTS: We have no
      good-quality evidence of the absolute effectiveness of haloperidol for people
      with long-term aggression. One study randomising 110 chronically aggressive
      people to three different antipsychotic drugs met the inclusion criteria. When
      haloperidol was compared with olanzapine or clozapine, skewed data (n=83) at high
      risk of bias suggested some advantage in terms of scale scores of unclear
      clinical meaning for olanzapine/clozapine for 'total aggression'. Data were
      available for only one other outcome, leaving the study early. When compared with
      other antipsychotic drugs, people allocated to haloperidol were no more likely to
      leave the study (1 RCT, n=110, RR 1.37, CI 0.84 to 2.24, low-quality evidence).
      Although there were some data for the outcomes listed above, there were no data
      on most of the binary outcomes and none on service outcomes (use of
      hospital/police), satisfaction with treatment, acceptance of treatment, quality
      of life or economics. AUTHORS' CONCLUSIONS: Only one study could be included and
      most data were heavily skewed, almost impossible to interpret and oflow quality.
      There were also some limitations in the study design with unclear description of
      allocation concealment and high risk of bias for selective reporting, so no firm
      conclusions can be made. This review shows how trials in this group of people are
      possible - albeit difficult. Further relevant trials are needed to evaluate use
      of haloperidol in treatment of long-term/persistent aggression in people living
      with psychosis.

PMID- 27889923
TI  - Normal radiological unossified hip joint space and femoral head size development
      during growth in 675 children and adolescents.
AB  - Evaluation of hip joint space width during child growth is important to aid in
      the early diagnosis of hip pathology in children. We established reference values
      for hip joint space and femoral head size for each age. Hip joint space
      development during growth was retrospectively investigated medial and cranial in
      1350 hip joints of children using standard anteroposterior supine plain pelvic
      radiographs. Maximum capital femoral epiphysis diameter and femoral radii were
      further more investigated. Hip joint space values show a slow decline during
      growth. Joint space was statistically significantly (p < 0.006) larger in boys
      than girls. Our hip joint space measurements on supine subjects seem slightly
      larger than those reported by Hughes on standing subjects. Evaluation of the
      femoral head diameter and the radii showed a size curve quite parallel to the
      known body growth charts. Radii medial and perpendicular to the physis are not
      statistically significantly different. We recommend to compare measurements of
      hip joint space at two locations to age dependent charts using the same imaging
      technique. During growth, a divergence in femoral head size from the expected
      values or loss of the spherical shape should raise the question of hip disorder.
      Clin. Anat. 30:267-275, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27889924
TI  - Dental ontogeny of a white shark embryo.
AB  - Unlike most viviparous vertebrates, lamniform sharks develop functional teeth
      during early gestation. This feature is considered to be related to their unique
      reproductive mode where the embryo grows to a large size via feeding on nutritive
      eggs in utero. However, the developmental process of embryonic teeth is largely
      uninvestigated. We conducted X-ray microcomputed tomography to observe the
      dentitions of early-, mid-, and full-term embryos of the white shark Carcharodon
      carcharias (Lamniformes, Lamnidae). These data reveal the ontogenetic change of
      embryonic dentition of the species for the first time. Dentition of the early
      term embryos (~45 cm precaudal length, PCL) is distinguished from adult dentition
      by 1) the presence of microscopic teeth in the distalmost region of the
      paratoquadrate, 2) a fang-like crown morphology, and 3) a lack of basal concavity
      of the tooth root. The "intermediate tooth" of early-term embryos is almost the
      same size as the adjacent teeth, suggesting that lamnoid-type heterodonty
      (lamnoid tooth pattern) has not yet been established. We also discovered that mid
      term embryos (~80 cm PCL) lack functional dentition. Previous studies have shown
      that the maternal supply of nutritive eggs in lamnoid sharks ceases during mid-
      to late-gestation. Thus, discontinuation of functional tooth development is
      likely associated with the completion of the oophagous (egg-eating) phase.
      Replacement teeth in mid-term embryos include both embryonic and adult-type
      teeth, suggesting that the embryo to adult transition in dental morphology occurs
      during this period. J. Morphol. 278:215-227, 2017. (c) 2016 Wiley
      Periodicals,Inc.

PMID- 27889925
TI  - Deletion of the vesicular acetylcholine transporter from
      pedunculopontine/laterodorsal tegmental neurons modifies gait.
AB  - Postural instability and gait disturbances, common disabilities in the elderly
      and frequently present in Parkinson's disease (PD), have been suggested to be
      related to dysfunctional cholinergic signaling in the brainstem. We investigated
      how long-term loss of cholinergic signaling from mesopontine nuclei influence
      motor behaviors. We selectively eliminated the vesicular acetylcholine
      transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei
      cholinergic neurons to generate mice with selective mesopontine cholinergic
      deficiency (VAChTEn1-Cre-flox/flox ). VAChTEn1-Cre-flox/flox mice did not show
      any gross health or neuromuscular abnormality on metabolic cages, wire-hang and
      grip-force tests. Young VAChTEn1-Cre-flox/flox mice (2-5 months-old) presented
      motor learning/coordination deficits on the rotarod; moved slower, and had
      smaller steps on the catwalk, but showed no difference in locomotor activity on
      the open field. Old VAChTEn1-Creflox/flox mice (13-16 months-old) showed more
      pronounced motor learning/balance deficits on the rotarod, and more pronounced
      balance deficits on the catwalk. Furthermore, old mutants moved faster than
      controls, but with similar step length. Additionally, old VAChT-deficient mice
      were hyperactive. These results suggest that dysfunction of cholinergic neurons
      from mesopontine nuclei, which is commonly seen in PD, has causal roles in motor
      functions. Prevention of mesopontine cholinergic failure may help to
      prevent/improve postural instability and falls in PD patients. Read the Editorial
      Highlight for this article on page 688.

PMID- 27889926
TI  - Nutritional ecology of wild Bornean orangutans (Pongo pygmaeus wurmbii) in a peat
      swamp habitat: Effects of age, sex, and season.
AB  - : The spatial and temporal variation in food abundance has strong effects on
      wildlife feeding and nutrition. This variation is exemplified by the peatland
      forests of Central Kalimantan, which are characterized by unpredictable fruiting
      fluctuations, relatively low levels of fruit availability, and low fruit periods
      (<3% of trees fruiting) that can last nearly a year. Challenged by these
      environments, large, arboreal frugivores like orangutans must periodically rely
      on non-preferred, lower-quality foods to meet their nutritional needs. We
      examined variation in nutrient intake among age-sex classes and seasons over a 7
      year period at the Tuanan Orangutan Research Station in Central Kalimantan. We
      conducted 2,316 full-day focal follows on 62 habituated orangutans (Pongo
      pygmaeus wurmbii). We found differences in total energy and macronutrient intake
      across age-sex classes, controlling for metabolic body mass. Intake of both total
      energy and macronutrients varied with fruit availability, and preference of
      dietary items increased with their nutritional quality. Foraging-related
      variables, such as day journey length, travel time, and feeding time, also varied
      among age-sex classes and with fruit availability. Our results add to the growing
      body of literature suggesting that great variation in foraging strategies exists
      among species, populations, and age-sex classes and in response to periods of
      resource scarcity. RESEARCH HIGHLIGHTS: The spatial and temporal variation in
      food abundance has strong effects on wildlife feeding and nutrition. Here we
      present the first long term study of the effects of variation in fruit
      availability and age/sex class on nutritional ecology of wild Bornean orangutans.
      We examined variation in nutrient intake of wild orangutans in living in a peat
      swamp habitat over a 7-year period at the Tuanan Orangutan Research Station in
      Central Kalimantan. We conducted 2,316 full-day focal follows on 62 habituated
      orangutans (Pongo pygmaeus wurmbii). We found differences in total energy and
      macronutrient intake across age-sex classes, controlling for metabolic body mass.
      Intake of both total energy and macronutrients varied with fruit availability,
      and preference of dietary items increased with their nutritional quality.
      Foraging-related variables, such as day journey length, travel time, and feeding
      time, also varied among age-sex classes and with fruit availability. Our results
      add to the growing body of literature suggesting that great variation in foraging
      strategies exists among species, populations, and age-sex classes and in response
      to periods of resource scarcity.

PMID- 27889927
TI  - Sp2 is the only glutamine-rich specificity protein with minor impact on
      development and differentiation in myelinating glia.
AB  - Oligodendrocytes and Schwann cells are the myelinating glia of the vertebrate
      nervous system and by generation of myelin sheaths allow rapid saltatory
      conduction. Previous in vitro work had pointed to a role of the zinc finger
      containing specificity proteins Sp1 and Sp3 as major regulators of glial
      differentiation and myelination. Here, we asked whether such a role is also
      evident in vivo using mice with specific deletions of Sp1 or Sp3 in myelinating
      glia. We also studied glia-specific conditional Sp2- and constitutive Sp4
      deficient mice to include all related glutamine-rich Sp factors into our
      analysis. Surprisingly, we did not detect developmental Schwann cell
      abnormalities in any of the mutant mice. Oligodendrocyte development and
      differentiation was also not fundamentally affected as oligodendrocytes were
      present in all mouse mutants and retained their ability to differentiate and
      initiate myelin gene expression. The most severe defect we observed was a 50%
      reduction in Mbp- and proteolipid protein 1 (Plp1)-positive differentiating
      oligodendrocytes in Sp2 mutants at birth. Unexpectedly, glial development
      appeared undisturbed even in the joint absence of Sp1 and Sp3. We conclude that
      Sp2 has a minor effect on the differentiation of myelinating glia, and that
      glutamine-rich Sp proteins are not essential regulators of the process.

PMID- 27889928
TI  - Elucidating the role of Cyclooxygenase-2 in the pathogenesis of oral lichen
      planus - an immunohistochemical study with supportive histochemical analysis.
AB  - OBJECTIVE: Oral lichen planus (OLP) is a chronic, inflammatory disorder that
      affects the oral mucous membrane. During an inflammatory response, several
      chemokines and cytokines are released by the cells of the immune system.
      Activation of MMPs, along with mast cell-derived chymase and tryptase, degrades
      the basement membrane structural proteins, resulting in basement membrane breaks.
      AIM: To investigate the association between the COX-2 expressions, presence of
      intact or degranulating mast cells within the connective tissue and the extent of
      basement membrane discontinuity in OLP cases. METHODS: This study included a
      total of 50 formalin-fixed paraffin-embedded specimens (FFPE) of histologically
      confirmed cases of idiopathic oral lichen planus. A retrospective cross-sectional
      analysis was carried out by immunohistochemistry to study the epithelial
      expression of COX-2 and by the use of special stains such as toluidine blue and
      periodic acid-Schiff (PAS) to study the mast cell count and basement membrane
      changes in the oral mucosal tissue, respectively. RESULTS: There was a
      significant (P = 0.03) association between the COX-2 expressions and mast cell
      count. As the intensity of COX-2 expression increased from mild to moderate or
      severe, the number of mast cell count almost doubled. CONCLUSION: Interaction
      between upregulation of COX-2, mast cell and basement membrane sets a vicious
      cycle which relates to the chronic nature of the disease. Inhibitors of COX-2 may
      reduce the inflammatory process preceding the immune dysregulation in OLP.

PMID- 27889929
TI  - Twenty-eight years of intestinal transplantation in Paris: experience of the
      oldest European center.
AB  - Our aim was to describe our achievements in pediatric intestinal transplantation
      (ITx) and define areas for improvement. After a period (1987-1990) of nine
      isolated small bowel transplants (SBTx) where only one patient survived with her
      graft, 110 ITx were performed on 101 children from 1994 to 2014: 60 SBTx, 45
      liver-small bowel, four multivisceral (three with kidneys), and one modified
      multivisceral. Indications were short bowel syndrome (36), motility disorders
      (30), congenital enteropathies (34), and others (1). Induction treatment was
      introduced in 2000. Patient/graft survival with a liver-containing graft or SBTx
      was, respectively, 60/41% and 46/11% at 18 years. Recently, graft survival at
      5/10 years was 44% and 31% for liver-containing graft and 57% and 44% for SBTx.
      Late graft loss occurred in 13 patients, and 7 of 10 retransplanted patients
      died. The main causes of death and graft loss were sepsis and rejection. Among
      the 55 currently living patients, 21 had a liver-containing graft, 19 a SBTx (17
      after induction), and 15 were on parenteral nutrition. ITx remains a difficult
      procedure, and retransplantation even more so. Over the long term, graft loss was
      due to rejection, over-immunosuppression was not a significant problem.
      Multicenter studies on immunosuppression and microbiota are urgently needed.

PMID- 27889930
TI  - Receptor tyrosine kinase amplification is predictive of distant metastasis in
      patients with oral squamous cell carcinoma.
AB  - This study aimed to clarify the genomic factors associated with the diagnosis and
      prognosis of oral squamous cell carcinoma via next-generation sequencing. We
      evaluated data from 220 cases of oral squamous cell carcinoma. Genomic DNA was
      eluted using formalin-fixed, paraffin-embedded samples, and targeted resequencing
      of 50 cancer-related genes was performed. In total, 311 somatic mutations were
      detected in 220 patients, consisting of 68 synonymous mutations and 243 non
      synonymous mutations. Genes carrying mutations included TP53, CDKN2A, and PIK3CA
      in 79 (35.9%), 35 (15.9%), and 19 patients (8.6%), respectively. Copy number
      analysis detected amplification of PIK3CA and AKT1 in 38 (17.3%) and 11 patients
      (5.0%), respectively. Amplification of receptor tyrosine kinases was found in 37
      patients (16.8%). Distant metastasis was noted in nine of 37 patients (24%) with
      receptor tyrosine kinase amplification, accounting for 43% of the 21 cases of
      distant metastasis. The cumulative 5-year survival rate was 64.6% in the receptor
      tyrosine kinase amplification group vs 85.2% in the no receptor tyrosine kinase
      amplification group. Moreover, we identified significantly poorer prognosis in
      the TP53 mutation/receptor tyrosine kinase amplification group, for which the
      cumulative 5-year survival rate was 41.6%. In conclusion, the results of this
      study demonstrated that receptor tyrosine kinase amplification is a prognostic
      factor for distant metastasis of oral squamous cell carcinoma, indicating the
      necessity of using next-generation sequencing in clinical sequencing.

PMID- 27889931
TI  - New use of prescription drugs prior to a cancer diagnosis.
AB  - PURPOSE: Cancers often have considerable induction periods. This confers a risk
      of reverse causation bias in studies of cancer risk associated with drug use, as
      early symptoms of a yet undiagnosed cancer might lead to drug treatment in the
      period leading up to the diagnosis. This bias can be alleviated by disregarding
      exposure for some time before the cancer diagnosis (lag time). We aimed at
      assessing the duration of lag time needed to avoid reverse causation bias.
      METHODS: We identified all Danish patients with incident cancer between 2000 and
      2012 (n = 353 087). Incident use of prescription drugs was assessed prior to
      their cancer diagnosis as well as among population controls (n = 1 402 400).
      Analyses were conducted for all cancers and for breast, lung, colon and prostate
      cancer individually. Further, analyses were performed for a composite measure of
      all incident drug use as well as for nine pre-specified individual drug classes,
      representing drug treatment likely to be prescribed for symptoms of the given
      cancers. RESULTS: The incidence rate for new drug treatment among cancer cases
      was stable around 130 per 1000 persons per month until 6 months prior to cancer
      diagnosis where it increased gradually and peaked at 434 in the month immediately
      preceding the cancer diagnosis. Considerable variation was observed among
      cancers, for example, breast cancer showed almost no such effect. The pre
      selected drug classes showed a stronger increase prior to cancer diagnoses than
      drugs overall. CONCLUSIONS: Incident use of drugs increases in the months prior
      to a cancer diagnosis. To avoid reverse causation, 6 months' lag time would be
      sufficient for most drug-cancer associations. (c) 2016 The Authors.
      Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

PMID- 27889932
TI  - Interaction of HEPES buffer with glass-ceramic scaffold: Can HEPES replace TRIS
      in SBF?
AB  - An international standard (ISO: 23317:2014) exists for the in vitro testing of
      inorganic biomaterials in simulated body fluid (SBF). This standard uses TRIS
      buffer to maintain neutral pH in SBF, but in our previous paper, we showed that
      the interaction of a tested glass-ceramic material with TRIS can produce false
      positive results. In this study, we evaluated whether the HEPES buffer, which
      also belongs to the group of Good's buffers, would be more suitable for SBF. We
      compared its suitability in two media: SBF with HEPES and demineralized water
      with HEPES. The tested scaffold (45S5 bioactive glass-based) was exposed to the
      media under a static-dynamic arrangement (solutions were replaced on a daily
      basis) for 15 days. Leachate samples were collected daily for the analysis of
      Ca2+ ions and Si (AAS), (PO4 )3- ions (UV-VIS), and to measure pH. The glass
      ceramic scaffold was analyzed by SEM/EDS, XRD, and WD-XRF before and after 0.3,
      1, 3, 7, 11, and 15 days of exposure. Our results confirmed the rapid selective
      dissolution of the glass-ceramic crystalline phase (Combeite) containing Ca2+
      ions due to the presence of HEPES, hydroxyapatite supersaturation being reached
      within 24 h in both solutions. These new results suggest that, like TRIS, HEPES
      buffer is not suitable for the in vitro testing of highly reactive inorganic
      biomaterials (glass, glass-ceramics). The ISO standard for such tests requires
      revision, but HEPES is not a viable alternative to TRIS buffer. (c) 2016 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 143-152, 2018.

PMID- 27889933
TI  - Development and field performance of nitrogen use efficient rice lines for
      Africa.
AB  - Nitrogen (N) fertilizers are a major input cost in rice production, and its
      excess application leads to major environmental pollution. Development of rice
      varieties with improved nitrogen use efficiency (NUE) is essential for
      sustainable agriculture. Here, we report the results of field evaluations of
      marker-free transgenic NERICA4 (New Rice for Africa 4) rice lines overexpressing
      barley alanine amino transferase (HvAlaAT) under the control of a rice stress
      inducible promoter (pOsAnt1). Field evaluations over three growing seasons and
      two rice growing ecologies (lowland and upland) revealed that grain yield of
      pOsAnt1:HvAlaAT transgenic events was significantly higher than sibling nulls and
      wild-type controls under different N application rates. Our field results clearly
      demonstrated that this genetic modification can significantly increase the dry
      biomass and grain yield compared to controls under limited N supply. Increased
      yield in transgenic events was correlated with increased tiller and panicle
      number in the field, and evidence of early establishment of a vigorous root
      system in hydroponic growth. Our results suggest that expression of the HvAlaAT
      gene can improve NUE in rice without causing undesirable growth phenotypes. The
      NUE technology described in this article has the potential to significantly
      reduce the need for N fertilizer and simultaneously improve food security,
      augment farm economics and mitigate greenhouse gas emissions from the rice
      ecosystem.

PMID- 27889935
TI  - The effects of becoming taller: direct and pleiotropic effects of artificial
      selection on plant height in Brassica rapa.
AB  - Plant height is an important trait for plant reproductive success. Plant height
      is often under pollinator-mediated selection, and has been shown to be correlated
      with various other traits. However, few studies have examined the evolutionary
      trajectory of plant height under selection and the pleiotropic effects of plant
      height evolution. We conducted a bi-directional artificial selection experiment
      on plant height with fast cycling Brassica rapa plants to estimate its
      heritability and genetic correlations, and to reveal evolutionary responses to
      artificial selection on height and various correlated traits. With the divergent
      lines obtained through artificial selection, we subsequently conducted pollinator
      choice assays and investigated resource limitation of fruit production. We found
      that plant height variation is strongly genetically controlled (with a realized
      heritability of 41-59%). Thus, plant height can evolve rapidly under phenotypic
      selection. In addition, we found remarkable pleiotropic effects in phenology,
      morphology, floral scent, color, nectar and leaf glucosinolates. Most traits were
      increased in tall-line plants, but flower size, UV reflection and glucosinolates
      were decreased, indicating potential trade-offs. Pollinators preferred plants of
      the tall selection lines over the short selection lines in both greenhouse
      experiments with bumblebees and field experiment with natural pollinators. We did
      not detect any differences in resource limitation between plants of the different
      selection lines. Overall, our study predicts that increased height should evolve
      under positive pollinator-mediated directional selection with potential trade
      offs in floral signals and herbivore defense.

PMID- 27889934
TI  - Vascular cell transcriptomic changes to exercise training differ directionally
      along and between skeletal muscle arteriolar trees.
AB  - EXT-induced arteriolar adaptations in skeletal muscle are heterogeneous because
      of spatial variations in muscle fiber type composition and fiber recruitment
      patterns during exercise. The purpose of this report is to summarize a series of
      experiments conducted to test the hypothesis that changes in vascular gene
      expression are signaled by alterations in shear stress resulting from increases
      in blood flow, muscle fiber type composition, and fiber recruitment patterns. We
      also report results from a follow-up study of Ankrd23, one gene whose expression
      was changed by EXT. We expected to see differences in magnitude of changes in
      gene expression along arteriolar trees and between/among arteriolar trees but
      similar directional changes. However, transcriptional profiles of
      arterioles/arteries from OLETF rats exposed to END or SIT reveal that EXT does
      not lead to similar directional changes in the transcriptome among arteriolar
      trees of different skeletal muscles or along arteriolar trees within a particular
      muscle. END caused the most changes in gene expression in 2A arterioles of soleus
      and white gastrocnemius with little to no changes in the FAs. Ingenuity Pathway
      Analysis across vessels revealed significant changes in gene expression in 18
      pathways. EXT increased expression of some genes (Shc1, desert hedgehog protein
      (Dhh), adenylate cyclase 4 (Adcy4), G protein-binding protein, alpha (Gnat1), and
      Bcl2l1) in all arterioles examined, but decreased expression of ubiquitin D (Ubd)
      and cAMP response element modulator (Crem). Many contractile and/or structural
      protein genes were increased by SIT in the gastrocnemius FA, but the same genes
      exhibited decreased expression in red gastrocnemius arterioles. Ankrd23 mRNA
      levels increased with increasing branch order in the gastrocnemius arteriolar
      tree and were increased 19-fold in gastrocnemius muscle FA by SIT. Follow-up
      experiments indicate that Ankrd23 mRNA level was increased 14-fold in cannulated
      gastrocnemius FA when intraluminal pressure was increased from 90 and 180 cm H2O
      for 4 hours. Also, Ankrd23-/- mice exhibit limited ability to form collateral
      arteries following femoral artery occlusion compared to WT mice (angioscore
      WT=0.18+/-0.03; Ankrd23-/- =0.04+/-0.01). Further research will be required to
      determine whether Ankrd23 plays an important role in mechanically induced
      vascular remodeling of the arterial tree in skeletal muscle.

PMID- 27889936
TI  - Abnormal heavy/light chain ratio after treatment is associated with shorter
      survival in patients with IgA myeloma.
AB  - Immunoglobulin (Ig) heavy/light chain (HLC) assays enable the separate
      quantification of the different light chain types of each Ig class. We
      retrospectively analyzed the correlation of heavy/light chain ratio (HLCR) with
      clinical status and its impact on outcome in 120 patients with multiple myeloma
      (MM). Abnormal HLCR was seen more frequently in patients with poorer myeloma
      response, and it appeared to be more sensitive for detecting clonality in IgA
      myeloma compared to IgG myeloma after treatment. Among the 85 patients who
      achieved >=VGPR, the patients remained HLCR abnormal were showed significantly
      shorter overall survival (OS) compared to those achieving a normal HLCR (not
      reached vs 55.5 months, P = 0.032). This correlation was seen in IgA myeloma
      patients (not reached vs 30.1 months, P = 0.014), but not in IgG myeloma patients
      when patients were analyzed separately. Univariate and multivariate analysis of
      factors that may affect survival identified abnormal HLCR at the best response as
      the only independent risk factor (hazard ratio, 4.7; 95% confidence interval, 1.4
      - 15.26; P = 0.012) for shorter OS in this subset of patients. This study
      highlighted the HLC assay as a prognostic predictor in patients with IgA myeloma.

PMID- 27889938
TI  - Respirology and the Asia-Pacific Century.

PMID- 27889937
TI  - Household-level risk factors for secondary influenza-like illness in a rural area
      of Bangladesh.
AB  - OBJECTIVE: To describe household-level risk factors for secondary influenza-like
      illness (ILI), an important public health concern in the low-income population of
      Bangladesh. METHODS: Secondary analysis of control participants in a randomised
      controlled trial evaluating the effect of handwashing to prevent household ILI
      transmission. We recruited index-case patients with ILI - fever (<5 years);
      fever, cough or sore throat (>=5 years) - from health facilities, collected
      information on household factors and conducted syndromic surveillance among
      household contacts for 10 days after resolution of index-case patients' symptoms.
      We evaluated the associations between household factors at baseline and secondary
      ILI among household contacts using negative binomial regression, accounting for
      clustering by household. RESULTS: Our sample was 1491 household contacts of 184
      index-case patients. Seventy-one percentage reported that smoking occurred in
      their home, 27% shared a latrine with one other household and 36% shared a
      latrine with >1 other household. A total of 114 household contacts (7.6%) had
      symptoms of ILI during follow-up. Smoking in the home (RRadj 1.9, 95% CI: 1.2,
      3.0) and sharing a latrine with one household (RRadj 2.1, 95% CI: 1.2, 3.6) or >1
      household (RRadj 3.1, 95% CI: 1.8-5.2) were independently associated with
      increased risk of secondary ILI. CONCLUSION: Tobacco use in homes could increase
      respiratory illness in Bangladesh. The mechanism between use of shared latrines
      and household ILI transmission is not clear. It is possible that respiratory
      pathogens could be transmitted through faecal contact or contaminated fomites in
      shared latrines.

PMID- 27889939
TI  - The performance of CPC/PLGA and Bio-Oss(r) for bone regeneration in healthy and
      osteoporotic rats.
AB  - The current study aimed to evaluate the biological performance of calcium
      phosphate cement (CPC) with polylactic-co-glycolic acid (PLGA) micro-particles
      and Bio-Oss(r) in ovariectomized and healthy rats. Thirty-two Wistar rats
      received alternating experimental CPC/PLGA and Bio-Oss(r) in femoral condyle
      defects in both femurs 6 weeks after ovariectomy (OVX, n = 16) or sham operation
      (SHAM, n = 16). Six weeks after OVX or SHAM surgery, bone morphology was analyzed
      by in vivo computed tomography (CT) to confirm osteoporotic bone condition.
      Analysis of bone formation and material remnants at 4 and 12 weeks after material
      implantation was performed by micro-CT, descriptive histology, histomorphometry
      and bone dynamics by fluorochrome labeling. The in vivo CT scans showed effective
      induction of osteoporotic bone condition by ovariectomy. Our data showed CPC/PLGA
      degraded relatively faster and more steadily. However, Bio-Oss(r) had
      significantly less material remnants and showed significantly more bone formation
      compared to CPC/PLGA. Overall, our data showed relatively high amounts of
      CPC/PLGA for each time point, hampering new bone formation within the defect
      area. Osteoporotic conditions proved to significantly affect degradation rates,
      but did not significantly influence bone formation. An osteoporotic bone
      condition affects degradation of CPC/PLGA, which is vital information for its
      potential use in osteoporotic conditions. (c) 2016 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 106B: 131-142, 2018.

PMID- 27889941
TI  - An Adductomic Approach to Identify Electrophiles In Vivo.
AB  - Human beings are exposed to many reactive electrophiles, both formed endogenously
      and from exogenous exposures. Such compounds could react with cellular
      biomolecules and form stable reaction products, adducts, at nucleophilic sites in
      proteins and DNA, constituting a risk for toxic effects. Adductomic approaches
      aim to study the totality of adducts, to specific biomolecules, by mass
      spectrometric screening. This Mini-Review focuses on the development and
      application of an adductomic approach for the screening of unknown adducts to N
      terminal valine (Val) in haemoglobin (Hb) by liquid chromatography tandem mass
      spectrometry (LC-MS/MS). The approach is based on the FIRE procedure, a modified
      Edman procedure for the analysis of adducts to N-terminal Val in Hb by LC-MS/MS.
      In the first application of the approach, samples from 12 smokers/non-smokers
      were screened for Hb adducts, and six previously identified adducts and 20
      unknown adducts were detected. To confirm the observation of the detected unknown
      adducts, targeted screenings were performed in larger sets of blood samples (n =
      50-120) from human cohorts. The majority of the previously detected unknown
      adducts was found in all analysed samples, with large interindividual variations
      in adduct levels. For structural identification of unknown adducts, a strategy
      using adductome LC-MS/MS data was formulated and applied. Six identified adducts
      correspond to ethylation and the precursor electrophiles ethyl vinyl ketone,
      glyoxal, methylglyoxal, acrylic acid and 1-octen-3-one. The observation of these
      adducts in human blood motivate further studies to evaluate possible
      contributions to health risks, as well as their potential as biomarkers of
      exposure.

PMID- 27889942
TI  - SWORD: a sharp performance and activity tool for inflammatory bowel disease
      surgeons with a blunt message.

PMID- 27889940
TI  - Sequencing of Australian wild rice genomes reveals ancestral relationships with
      domesticated rice.
AB  - The related A genome species of the Oryza genus are the effective gene pool for
      rice. Here, we report draft genomes for two Australian wild A genome taxa: O.
      rufipogon-like population, referred to as Taxon A, and O. meridionalis-like
      population, referred to as Taxon B. These two taxa were sequenced and assembled
      by integration of short- and long-read next-generation sequencing (NGS) data to
      create a genomic platform for a wider rice gene pool. Here, we report that,
      despite the distinct chloroplast genome, the nuclear genome of the Australian
      Taxon A has a sequence that is much closer to that of domesticated rice (O.
      sativa) than to the other Australian wild populations. Analysis of 4643 genes in
      the A genome clade showed that the Australian annual, O. meridionalis, and
      related perennial taxa have the most divergent (around 3 million years) genome
      sequences relative to domesticated rice. A test for admixture showed possible
      introgression into the Australian Taxon A (diverged around 1.6 million years ago)
      especially from the wild indica/O. nivara clade in Asia. These results
      demonstrate that northern Australia may be the centre of diversity of the A
      genome Oryza and suggest the possibility that this might also be the centre of
      origin of this group and represent an important resource for rice improvement.

PMID- 27889943
TI  - A clinicopathological study of the oral lesions of Cowden disease.
AB  - BACKGROUND: Cowden disease is a multisystemic cancer predisposition disorder,
      inherited in an autosomal dominant pattern. Cutaneous and visceral lesions are
      either malignant tumours or are believed to represent hamartomatous growths.
      Mucocutaneous lesions are present on almost 100% of affected individuals.
      Nonetheless, some authors consider that the mucocutaneous manifestations of
      Cowden disease are, in reality, viral warts at distinct steps of evolution. There
      are only a few studies regarding the oral manifestations of Cowden disease.
      OBJECTIVES: To study the oral manifestations of Cowden disease in nine patients
      clinically and histopathologically. METHODS: The oral mucosal aspects of nine
      patients with clinical diagnosis of Cowden disease were photographed, and
      biopsies were taken from typical lesions. RESULTS: All biopsied lesions depicted
      histopathological aspects suggestive of viral warts at distinct steps of
      development: incipient, well established and in regression. CONCLUSION: Our
      findings seem to reinforce the poorly understood hypothesis that the
      mucocutaneous manifestations of Cowden disease are in reality viral warts.
      Additional studies are needed to explain why a syndrome caused by the mutation of
      a tumour suppression gene may cause propensity to warts.

PMID- 27889944
TI  - Intramembrane proteases as drug targets.
AB  - Proteases are considered attractive drug targets. Various drugs targeting
      classical, soluble proteases have been approved for treatment of human disease.
      Intramembrane proteases (IMPs) are a more recently discovered group of
      proteolytic enzymes. They are embedded in lipid bilayers and their active sites
      are located in the plane of a membrane. All four mechanistic families of IMPs
      have been linked to disease, but currently, no drugs against IMPs have entered
      the market. In this review, I will outline the function of IMPs with a focus on
      the ones involved in human disease, which includes Alzheimer's disease, cancer,
      and infectious diseases by microorganisms. Inhibitors of IMPs are known for all
      mechanistic classes, but are not yet very potent or selective - aside from those
      targeting gamma-secretase. I will here describe the different features of IMP
      inhibitors and discuss a list of issues that need attention in the near future in
      order to improve the drug development for IMPs.

PMID- 27889945
TI  - Social media in colorectal surgery.
AB  - The engagement of social media in healthcare continues to expand. For members of
      the colorectal community, social media has already made a significant impact on
      practice, education and patient care. The applications are unique such that they
      provide a platform for instant communication and information sharing with other
      users worldwide. The purpose of this article is to provide an overview of how
      social media has the potential to change clinical practice, training, research
      and patient care in colorectal surgery.

PMID- 27889947
TI  - Pathological Findings of NASH and NAFLD: for Guidebook of NASH and NAFLD, 2015:
      The Japan Society of Hepatology.
AB  - Nonalcoholic fatty liver disease (NAFLD) is an increasingly common chronic liver
      disease worldwide. NAFLD comprises a variety of clinical and histopathological
      changes that can be broadly divided into nonalcoholic fatty liver (NAFL, simple
      steatosis) and nonalcoholic steatohepatitis (NASH). The differential diagnosis
      between NAFL and NASH is important because NASH is a more advanced form. This
      diagnosis therefore determines the prognosis and therapeutic management. At
      present the interpretation of NASH is made based on the histopathological
      features of steatohepatitis, i.e. 'steatosis', 'lobular inflammation', hepatocyte
      'ballooning, 'Mallory-Denk bodies' and 'fibrosis'. Here, we summarize the
      pathological findings guidelines for NASH as it was already published in 2015 in
      Japanese in the clinical guidebook organized by the Japan Society of Hepatology.

PMID- 27889946
TI  - Combined fibrinogen and neutrophil-lymphocyte ratio as a prognostic marker of
      advanced esophageal squamous cell carcinoma.
AB  - Patients with advanced esophageal squamous cell carcinoma (ESCC) is received
      chemoradiotherapy or chemotherapy for clinical management. However, it is
      difficult to predict tumor response and prognosis using blood markers before
      starting treatments. The purpose of this study was to investigate the pre
      treatment plasma fibrinogen and neutrophil-lymphocyte ratio (NLR) in patients
      with advanced ESCC treated with chemoradiotherapy or chemotherapy, and to assess
      the clinical utility of a combined score using these blood markers, named as the
      F-NLR (fibrinogen and NLR) score, as a predictor of tumor response and prognosis.
      A total of 98 advanced ESCC patients, treated with chemoradiotherapy or
      chemotherapy, were classified into three groups: F-NLR score of 2, having both
      hyperfibrinogenemia (>400 mg/dL) and high NLR (>3.0), score of 1, one of these
      hematological abnormalities, and score of 0, having neither hyperfibrinogenemia
      nor high NLR. Fibrinogen and NLR were significantly higher in the progressive
      disease (PD) group than the non-PD group (P = 0.0419, and P = 0.0001,
      respectively). A significantly higher F-NLR score was found in the PD group than
      the non-PD group (P = 0.0140). Overall survival was significantly lower in
      patients with an F-NLR score of 2 than in those with an F-NLR score of 0 or 1 (P
      < 0.0001). Multivariate analysis showed that the F-NLR score was one of the
      independent prognostic factors (P = 0.0081). Our study demonstrates that the F
      NLR score is promising as a predictive marker for therapeutic effects and
      prognosis in patients with advanced ESCC.

PMID- 27889948
TI  - A new sequence data set of SSU rRNA gene for Scleractinia and its phylogenetic
      and ecological applications.
AB  - Scleractinian corals (i.e. hard corals) play a fundamental role in building and
      maintaining coral reefs, one of the most diverse ecosystems on Earth.
      Nevertheless, their phylogenies remain largely unresolved and little is known
      about dispersal and survival of their planktonic larval phase. The small subunit
      ribosomal RNA (SSU rRNA) is a commonly used gene for DNA barcoding in several
      metazoans, and small variable regions of SSU rRNA are widely adopted as barcode
      marker to investigate marine plankton community structure worldwide. Here, we
      provide a large sequence data set of the complete SSU rRNA gene from 298
      specimens, representing all known extant reef coral families and a total of 106
      genera. The secondary structure was extremely conserved within the order with few
      exceptions due to insertions or deletions occurring in the variable regions.
      Remarkable differences in SSU rRNA length and base composition were detected
      between and within acroporids (Acropora, Montipora, Isopora and Alveopora)
      compared to other corals. The V4 and V9 regions seem to be promising barcode loci
      because variation at commonly used barcode primer binding sites was extremely
      low, while their levels of divergence allowed families and genera to be
      distinguished. A time-calibrated phylogeny of Scleractinia is provided, and
      mutation rate heterogeneity is demonstrated across main lineages. The use of this
      data set as a valuable reference for investigating aspects of ecology, biology,
      molecular taxonomy and evolution of scleractinian corals is discussed.

PMID- 27889949
TI  - Undercarboxylated osteocalcin can predict insulin secretion ability in type 2
      diabetes.
AB  - It has been reported that there is an intimate relationship between diabetes and
      bone metabolism including undercarboxylated osteocalcin (ucOC). In contrast, data
      on the relationship between ucOC and glucose metabolism are limited in type 2
      diabetes. We recruited 50 Japanese patients with type 2 diabetes, and examined
      the association with ucOC on the insulin secretion, evaluated by both glucagon
      loading test and meal tolerance test. UcOC was shown to correlate positively with
      the change in C-peptide response in the glucagon loading test and C-peptide
      response after eating a meal (P = 0.025, P = 0.047). Therefore, ucOC reflects the
      reserve capacity of beta-cell function, such as the bolus insulin secretion
      ability in patients with type 2 diabetes.

PMID- 27889950
TI  - Retinopathy: A sign of cerebral small vessel disease in diabetes?
AB  - Retinal microvascular abnormalities may be useful predictive imaging marker for
      cerebral small vessel disease. Learning from retinal signs may provide clues to
      understanding pathophysiology of lacunar stroke and subclinical cerebrovascular
      diseases in diabetic patients.

PMID- 27889951
TI  - Performance of the High-dimensional Propensity Score in a Nordic Healthcare
      Model.
AB  - The high-dimensional propensity score (hdPS) is increasingly used as a tool to
      adjust for confounding in observational studies of drug effects. It was developed
      within very rich data sources, for example the American claims databases. Thus,
      it is unknown whether it can be applied in settings that provide little more than
      primary care prescriptions and diagnoses from hospital contacts, as in the Nordic
      data sources. Our objective was to evaluate the performance of hdPS under such
      circumstances. As our case, we chose the association between use of selective
      cyclooxygenase-2 inhibitors (coxibs) and traditional NSAIDs (tNSAIDs) and the
      risk of upper GI bleeding. Using Danish health registries, we identified 110,285
      incident users of coxibs and 575,980 incident users of tNSAIDs and followed them
      for 90 days with respect to the occurrence of serious upper GI bleeding. Data
      were analysed using Cox regression, estimating the coxib/tNSAID hazard ratio
      (HR). Values below 1.00 indicate a lower estimated hazard with coxibs. We build
      hdPS models with inclusion of up to 500 diagnosis and 500 prescription drug
      covariates. The crude HR was 1.76 (95% confidence interval: 1.57-1.97),
      decreasing to 1.12 (1.00-1.26) and 0.99 (0.88-1.12) after adjustment for age and
      sex and 11 pre-selected confounders, respectively. A hdPS with inclusion of 500
      most prevalent diagnoses and 500 most prevalent prescription drugs resulted in a
      HR of 0.89 (0.77-1.02). These estimates were consistently lower when the analysis
      was restricted to non-users of low-dose aspirin. The estimate based on 500
      diagnoses alone was higher than an estimate based on 500 prescription drugs alone
      (0.99 versus 0.91). We conclude that hdPS does work within a Nordic setting that
      prescription data are more effective than diagnosis data in achieving confounder
      adjustment and that hdPS seems more effective than simple confounder adjustment
      by variables selected on the basis of clinical reasoning.

PMID- 27889952
TI  - Effects of different doses of 2,3-dimercaptosuccinic acid-modified Fe2 O3
      nanoparticles on intercalated discs in engineered cardiac tissues.
AB  - Although iron oxide nanoparticles (IRONs) were applied in clinical magnetic
      resonance imaging in vivo and magnetic tissue engineering in vitro widely, the
      underlying effects of IRONs on the development of cardiomyocytes especially the
      intercellular junctions, intercalated discs (IDs), remain an unknown issue. Given
      the critical role of three-dimensional (3D) engineered cardiac tissues (ECTs) in
      evaluation of nanoparticles toxicology, it remained necessary to understand the
      effects of IRONs on IDs assembly of cardiomyocytes in 3D environment. In this
      study, we first reconstituted collagen/Matrigel based ECTs in vitro and prepared
      IRONs with 2,3-dimercaptosuccinic acid (DMSA-IRONs). We found that the
      internalization of DMSA-IRONs by cardiac cells in dose-dependent manner was not
      associated with the cell distribution in 3D environment by determination of
      Prussian blue staining and transmission electronic microscopy. Significantly,
      through determination of western blotting and immunofluorescence of connexin 43,
      N-cadherin, desmoplakin, and plakoglobin, DMSA-IRONs enhanced the assembly of gap
      junctions, decreased mechanical junctions (adherens junctions and desmosomes) of
      cardiac cells but not in dose-dependent manner in ECTs at seventh day. In
      addition, DMSA-IRONs increased the vesicles secretion of cardiac cells in ECTs
      apparently compared to control groups. Overall, we conclude that the
      internalization of DMSA-IRONs by cardiac cells in dose-dependent manner enhanced
      the assembly of electrochemical junctions and decreased the mechanical related
      microstructures. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater, 106B: 121-130, 2018.

PMID- 27889954
TI  - Invasive pulmonary aspergillosis in a patient with metastatic non-small cell lung
      cancer after treatment with gefitinib.

PMID- 27889953
TI  - Ecology under lake ice.
AB  - Winter conditions are rapidly changing in temperate ecosystems, particularly for
      those that experience periods of snow and ice cover. Relatively little is known
      of winter ecology in these systems, due to a historical research focus on summer
      'growing seasons'. We executed the first global quantitative synthesis on under
      ice lake ecology, including 36 abiotic and biotic variables from 42 research
      groups and 101 lakes, examining seasonal differences and connections as well as
      how seasonal differences vary with geophysical factors. Plankton were more
      abundant under ice than expected; mean winter values were 43.2% of summer values
      for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer
      zooplankton density. Dissolved nitrogen concentrations were typically higher
      during winter, and these differences were exaggerated in smaller lakes. Lake size
      also influenced winter-summer patterns for dissolved organic carbon (DOC), with
      higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation,
      phytoplankton and zooplankton community composition showed few systematic
      differences between seasons, although literature suggests that seasonal
      differences are frequently lake-specific, species-specific, or occur at the level
      of functional group. Within the subset of lakes that had longer time series,
      winter influenced the subsequent summer for some nutrient variables and
      zooplankton biomass.

PMID- 27889955
TI  - Successful desensitization of pemetrexed-induced anaphylaxis in a patient with
      malignant mesothelioma.

PMID- 27889958
TI  - ACE2 and the Homolog Collectrin in the Modulation of Nitric Oxide and Oxidative
      Stress in Blood Pressure Homeostasis and Vascular Injury.
AB  - SIGNIFICANCE: Hypertension is the leading risk factor causing mortality and
      morbidity worldwide. Angiotensin (Ang) II, the most active metabolite of the
      renin-angiotensin system, plays an outstanding role in the pathogenesis of
      hypertension and vascular injury. Activation of angiotensin converting enzyme 2
      (ACE2) has shown to attenuate devastating effects of Ang II in the cardiovascular
      system by reducing Ang II degradation and increasing Ang-(1-7) generation leading
      to Mas receptor activation. Recent Advances: Activation of the ACE2/Ang-(1-7)/Mas
      receptor axis reduces hypertension and improves vascular injury mainly through an
      increased nitric oxide (NO) bioavailability and decreased reactive oxygen species
      production. Recent studies reported that shedding of the enzymatically active
      ectodomain of ACE2 from the cell surface seems to regulate its activity and
      serves as an interorgan communicator in cardiovascular disease. In addition,
      collectrin, an ACE2 homolog with no catalytic activity, regulates blood pressure
      through an NO-dependent mechanism. CRITICAL ISSUES: Large body of experimental
      data confirmed sustained beneficial effects of ACE2/Ang-(1-7)/Mas receptor axis
      activation on hypertension and vascular injury. Experimental studies also suggest
      that activation of collectrin might be beneficial in hypertension and endothelial
      dysfunction. Their role in clinical hypertension is unclear as selective and
      reliable activators of both axes are not yet available. FUTURE DIRECTIONS: This
      review will highlight the results of recent research progress that illustrate the
      role of both ACE and collectrin in the modulation of NO and oxidative stress in
      blood pressure homeostasis and vascular injury, providing evidence for the
      potential therapeutic application of ACE2 and collectrin in hypertension and
      vascular disease. Antioxid. Redox Signal. 26, 645-659.

PMID- 27889959
TI  - Fumaric Acid Esters Attenuate Secondary Degeneration after Spinal Cord Injury.
AB  - Spinal cord injury (SCI) causes permanent changes in motor, sensory, and
      autonomic functions. Unfortunately, there are no stable cures and current
      treatments include surgical decompression, methylprednisolone, and hemodynamic
      control that lead to modest function recovery. Fumaric acid esters (FAEs) were
      firstly used in the management of an immunological skin disorder, such as
      psoriasis. Because of their potent anti-inflammatory effects, they have been
      introduced in multiple sclerosis (MS). Investigation has shown not only an anti
      inflammatory, but also supposed neuroprotective mechanism of action. The goal of
      the present work was to evaluate the potential beneficial effects of dimethyl
      fumarate (DMF) and monomethyl fumarate (MMF) in a mouse model of traumatic SCI.
      SCI was produced by extradural compression for 1 min of the spinal cord at the T6
      7 level using an aneurysm clip, and DMF and MMF (both at 30 mg/kg) were
      administered by oral gavage to the mice 1 and 6 h after SCI. For locomotor
      activity, study mice were treated with FAEs once daily for 10 days. We observed
      that mice treated with DMF exhibited a significant and sustained recovery of
      motor function. FAEs significantly reduced the severity of inflammation by a
      modulation of pro-inflammatory cytokines and apoptosis factors, and increased
      neutrophic factors such as anti-brain-derived neurotrophic factor (BDNF), anti
      glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT3). Our
      results showed important protective effects of DMF in an animal model of SCI,
      considerably improving recovery of motor function, possibly by reducing the
      secondary inflammation and tissue injury that characterize this model. DMF may
      constitute a promising target for future SCI therapies.

PMID- 27889957
TI  - Acute or Delayed Treatment with Anatabine Improves Spatial Memory and Reduces
      Pathological Sequelae at Late Time-Points after Repetitive Mild Traumatic Brain
      Injury.
AB  - Traumatic brain injury (TBI) has chronic and long-term consequences for which
      there are currently no approved pharmacological treatments. We have previously
      characterized the chronic neurobehavioral and pathological sequelae of a mouse
      model of repetitive mild TBI (r-mTBI) through to 2 years post-TBI. Despite the
      mild nature of the initial insult, secondary injury processes are initiated that
      involve neuroinflammatory and neurodegenerative pathways persisting and
      progressing for weeks and months post-injury and providing a potential window of
      opportunity for therapeutic intervention. In this study we examined the efficacy
      of a novel anti-inflammatory compound, anatabine, in modifying outcome after TBI.
      Our model of r-mTBI involves a series of five mild impacts (midline impact at 5
      m/sec, 1 mm strike depth, 200 msec dwell time) with an interval of 48 h.
      Anatabine treatment was administered starting 30 min after injury and was
      delivered continuously through drinking water. At 6 months after TBI, anatabine
      treatment improved spatial memory in injured mice. Nine months after TBI, a
      cohort of mice was euthanized for pathological analysis that revealed reductions
      in astroglial (glial fibrillary acid protein, GFAP) and microglial (ionized
      calcium-binding adapter molecule 1, IBA1) responses in treated, injured animals.
      Treatments for the remaining mice were then crossed-over to assess the effects of
      late treatment administration and the effects of treatment termination. Nine
      months following crossover the remaining mice showed no effect of injury on their
      spatial memory, and whereas pathological analysis showed improvements in mice
      that had received delayed treatment, corpus callosum IBA1 increased in post
      crossover placebo r-mTBI mice. These data demonstrate efficacy of both early and
      late initiation of treatment with anatabine in improving long term behavioral and
      pathology outcomes after mild TBI. Future studies will characterize the treatment
      window, the time course of treatment needed, and the dose needed to achieve
      therapeutic levels of anatabine in humans after injury.

PMID- 27889960
TI  - Current Management in Transurethral Therapy of Benign Prostatic Obstruction in
      Patients on Oral Anticoagulation: A Worldwide Questionnaire.
AB  - OBJECTIVE: To assess the current treatment of benign prostatic obstruction (BPO)
      in patients on ongoing oral anticoagulation (OA). METHODS: An Internet survey was
      sent to all active members of the Endourological Society. The survey contained 32
      questions regarding transurethral treatment of BPO in patients on ongoing OA,
      different techniques, and arising complications. RESULTS: Out of all members (n =
      2000) of the Endourological Society, 133 participated in our survey. Eighty-eight
      percent of the participants indicated to perform transurethral therapy of BPO on
      ongoing OA, whereas 60% of this group temporarily pause the OA during the
      intervention. Sixteen percent perform >30 transurethral interventions of BPO on
      ongoing OA per year. Most operations are performed under continuation of aspirin
      (58.2%). The continuation of adenosine diphosphate (ADP)-receptor inhibitors
      (22.1%), vitamin K antagonists (18.9%), factor Xa inhibitors (15.6%), or the
      combination of two oral anticoagulants (16.4%) is continued less often. The
      decision for the operation on ongoing OA is usually approved by the cardiologist
      (58%) or it cannot be stopped in case of emergency (29%). GreenLight laser (39%)
      was the most frequently used technique on ongoing OA, followed by monopolar or
      bipolar transurethral resection of the prostate (35%) as well as other sources of
      laser [holmium (12%), thulium (12%), diode laser (2%)]. Although OA was continued
      during the interventions, cardiovascular complications were observed in 31.6%.
      CONCLUSIONS: Current practice shows that the majority of a representative group
      of the Endourological Society members perform transurethral therapy of BPO in
      patients on ongoing OA. The incidence of perioperative complications under
      transurethral therapy of BPO on ongoing OA is lower than previously assumed.

PMID- 27889961
TI  - Industry sponsorship and positive outcome in vascular and endovascular randomised
      trials.

PMID- 27889973
TI  - First aid and emergencies in nursing.
AB  - This article will look at first aid and examine whether and where first aid may
      be applied to present-day nursing theory and practice.

PMID- 27889956
TI  - Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide
      Metabolism, Anemia.
AB  - SIGNIFICANCE: Recent clinical evidence identified anemia to be correlated with
      severe complications of cardiovascular disease (CVD) such as bleeding,
      thromboembolic events, stroke, hypertension, arrhythmias, and inflammation,
      particularly in elderly patients. The underlying mechanisms of these
      complications are largely unidentified. Recent Advances: Previously, red blood
      cells (RBCs) were considered exclusively as transporters of oxygen and nutrients
      to the tissues. More recent experimental evidence indicates that RBCs are
      important interorgan communication systems with additional functions, including
      participation in control of systemic nitric oxide metabolism, redox regulation,
      blood rheology, and viscosity. In this article, we aim to revise and discuss the
      potential impact of these noncanonical functions of RBCs and their dysfunction in
      the cardiovascular system and in anemia. CRITICAL ISSUES: The mechanistic links
      between changes of RBC functional properties and cardiovascular complications
      related to anemia have not been untangled so far. FUTURE DIRECTIONS: To allow a
      better understanding of the complications associated with anemia in CVD, basic
      and translational science studies should be focused on identifying the role of
      noncanonical functions of RBCs in the cardiovascular system and on defining
      intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to
      CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718
      742.

PMID- 27889975
TI  - [Prof. Edit Glaz has turned 90].

PMID- 27889976
TI  - [Academician Prof. Dr. Jozsef Tigyi, biophysicist (1926-2016)].

PMID- 27889974
TI  - [Vitamin D metabolism and signaling in human hepatocellular carcinoma and
      surrounding non-tumorous liver].
AB  - INTRODUCTION: 1,25-Dihydroxy vitamin D3 mediates antitumor effects in
      hepatocellular carcinoma. AIM: We examined mRNA and protein expression
      differences in 1,25-Dihydroxy vitamin D3-inactivating CYP24A1, mRNA of activating
      CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and
      surrounding non-tumorous liver. METHODS: Snap-frozen tissues from 13 patients
      were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded
      tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA
      expression was measured by RT-PCR, CYP24A1 protein was detected by
      immunohistochemistry. RESULTS: Expression of VDR and CYP27B1 was significantly
      lower in hepatocellular carcinoma compared with non-tumorous liver (p<0.05). The
      majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non
      tumorous liver. The gene activation was followed by CYP24A1 protein synthesis.
      CONCLUSIONS: The presence of CYP24A1 mRNA and the reduced expression of VDR and
      CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased
      bioavailability of 1,25-Dihydroxy vitamin D3, providing an escape mechanism from
      the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

PMID- 27889979
TI  - [Ancient medical treatments for liver disease].

PMID- 27889978
TI  - [Analysis of plantar pressure patterns among obese population].
AB  - INTRODUCTION: Although the role of body weight on foot health and load has been
      widely documented in research, the effect of the extra load due to body weight on
      plantar pressure characteristics is not well known. AIM: The aim of this study
      was to evaluate the impact of obesity on plantar pressure patterns among the
      working-age population. METHOD: 180 participants were involved. Two groups were
      evaluated according to body mass index categories regarding eight regions of the
      plantar area, focusing on the following parameters: contact area, maximum
      pressure and peak pressure. RESULTS: Compared with non-obese subjects, the peak
      pressure was the highest on the midfoot (p<0.001) and the forefoot (p<0.001).
      Regarding the maximum force, significant statistical difference was detected on
      the toes (p<0.001), with a value lower among the obese group. The contact area on
      the total foot and the midfoot was lower among the non-obese subjects (p<0.001).
      CONCLUSIONS: Loading is greatly increasing on the whole plantar area, especially
      at the midfoot and the forefoot region. Orv. Hetil., 2016, 157(48), 1919-1925.

PMID- 27889980
TI  - [The importance of "free" nucleic acids in the non-invasive diagnostics].
AB  - There is a great interest to determine the physiological role of "free" nucleic
      acids, and to use them in the clinical diagnostics. These could be DNA, mRNA,
      microRNA and long non-coding RNA molecules, they are in the body fluids, like
      serum, tear, saliva, etc. Their exact role in the normal and pathological
      physiological processes is still in the focus of the research, while their use in
      the diagnostics is becoming more and more important. The use of "free" DNA in the
      non-invasive prenatal diagnosis is the first clinical application of the new
      generation sequencers, these methods are able to reach 99.9% specificity and
      sensitivity for the detection of the most common trisomies. There are promising
      results in their use in the diagnosis and classification of heart and
      cardiovascular diseases. In oncology the possibility to use the "liquid biopsy"
      captured the attention of not only researchers and clinicians, but the whole
      community. There is not enough data until today for the clinical utility and
      applicability of these methods. Orv. Hetil., 2016, 157(48), 1900-1909.

PMID- 27889981
TI  - Chimeric Trojan Protein Insertion in Lentiviral Membranes Makes Lentiviruses
      Susceptible to Neutralization by Anti-Tetanus Serum Antibodies.
AB  - This study describes the initial testing of a novel strategy for neutralization
      of lentiviruses using the fundamental biology of enveloped viruses' assembly and
      budding. In the field of gene therapy, viral vector surface proteins have been
      manipulated in order to redirect host cell specificity by alteration of pseudo
      types. This study tested whether known viral pseudo-typing proteins or surface
      proteins known to be recruited to the human immunodeficiency virus (HIV) envelope
      could be engineered to carry neutralizing epitopes from another microorganism
      onto the lentiviral surface. The results identify ICAM1 as a novel vehicle for
      lentiviral pseudo-typing. Importantly, the study shows that in a model lentiviral
      system, ICAM1 can be engineered in chimeric form to result in expression of a
      fragment of the tetanus toxoid on the viral membrane and that these viruses can
      then be neutralized by human serum antibodies protective against tetanus. This
      raises the possibility of delivering chimeric antigens as a gene therapy in HIV
      infected patients.

PMID- 27889985
TI  - Night nurse practitioners are not 'mini-doctors'.
AB  - It was felt that certain procedures that are currently being performed by junior
      doctors at night could be performed equally well, if not better, by appropriately
      educated night nurse practitioners. This article describes an innovative
      programme that was developed to produce accountable nurse practitioners.

PMID- 27889987
TI  - Hearing impairment in elderly hospital residents.
AB  - The provision of high quality nursing care for dependent elderly people is a
      daunting challenge to the profession. This survey focuses on the frequently
      neglected area of impaired hearing among elderly hospital residents and evaluates
      the service provided by one health board.

PMID- 27889990
TI  - Behaviour at the scene of an accident.
AB  - This article examines how nurses should behave at the scene of an accident
      without the back-up of primary care apparatus and highlights the nurse aid
      management of road accidents.

PMID- 27889982
TI  - External Validation and Evaluation of Reliability and Validity of the Triple D
      Score to Predict Stone-Free Status After Extracorporeal Shockwave Lithotripsy.
AB  - OBJECTIVE: The Triple D scoring system is defined as novel and simple nomogram
      using the main parameters (skin-to-stone distance, stone density, and volume) to
      indicate most appropriate patients for extracorporeal shockwave lithotripsy
      (SWL). We aimed to evaluate the accuracy of the Triple D scoring system in
      predicting SWL success rates. PATIENTS AND METHODS: In two tertiary academic
      centers, charts were retrospectively analyzed of patients who had, between
      January 2014 and May 2016, been treated by SWL for radiopaque kidney stones. A
      total of 200 patients were enrolled into the study. Parameters were calculated
      for each of the three specified variables. Since one point was assigned for any
      parameter that was less than the cutoff value, Triple D scores ranged from 0
      (worst) to 3 (best). RESULTS: Stone-free status was achieved in 115 patients
      (57.5%), and 85 patients had one or more residual fragments (42.5%). Differences
      in stone characteristics, including stone location, density, and volume, were
      statistically significant in patients whether SWL achieved stone-free status or
      not (p < 0.001, p < 0.001, and p < 0.001, respectively). Triple D scores were
      significantly higher in patients treated with SWL compared with patients in whom
      SWL failed (p < 0.001). Triple D scores of 0, 1, 2, and 3 correlated with stone
      free rates of 41.7%, 33.7%, 69.4%, and 97%, respectively. The multivariate
      analyses revealed that Triple D score and stone location were identified as
      independent factors affecting SWL success (p < 0.001 and p = 0.008,
      respectively). The mean number of SWL sessions was significantly higher in
      patients with SWL failure (p = 0.003). CONCLUSION: Our study externally validates
      that the Triple D scoring system is associated with SWL success in the treatment
      of renal and ureteral stones. Further studies are warranted to assess clinical
      usefulness and the accuracy of this nomogram in different patient groups.

PMID- 27889992
TI  - Extended role of the nurse in ICU.
AB  - There is much controversy over the definition of a nurse's extended role. This
      article gives a brief overview of the results of a research survey that examined
      nurses' attitudes to the practice of extended roles in intensive care units.

PMID- 27889993
TI  - Experimental, Theoretical and Biological Activity of a Triazonine- Derivative on
      Left Ventricular Pressure.
AB  - BACKGROUND: There are data indicating that several azonine-derivatives may exert
      effects on some biological systems; however, there is very low information on the
      biological activity induced by these compounds on left ventricular pressure.
      OBJECTIVE: The aim of this study was to synthesize and evaluate the biological
      activity of new triazoninederivative on left ventricular pressure. MATERIAL AND
      METHODS: The first stage involved: 1) preparation of two azepine-benzamide
      derivatives (Z or E) by reaction of the nitrobenzoyl azide with adrenosterone;
      and 2) reaction of (Z)-azepine-benzamide derivative with ethylenediamine to form
      the triazonine derivative. The structure of compounds was confirmed by
      spectroscopy and spectrometry data. The second stage involved the biologic
      activity on left ventricular pressure was evaluated in a model of rat heart
      isolated. In addition, some physicochemical parameters were evaluated to
      characterize the possible molecules involved in its effect. RESULTS: The results
      showed that only the triazonine increased left ventricular pressure via androgen
      receptor. CONCLUSIONS: In conclusion, this phenomenon is conditioned by the
      functional groups involved in the chemical structure of triazonine derivative and
      their interaction with residues of amino acids involved on the androgen receptor
      surface.

PMID- 27889994
TI  - PD-1/PD-Ls: A New Target for Regulating Immunopathogenesis in Central Nervous
      System Disorders.
AB  - BACKGROUND: Immune responses including Microglia and macrophage activation and
      peripheral immune cells infiltration have been founded in the central nervous
      system (CNS) in recent years. Thus, the traditional view of the adult brain as an
      immune-privileged organ has been changed. METHODS: A systematic literature search
      was performed using Pubmed and Embase electronic databases without any
      limitations for a retrospective analysis. RESULTS: The increase a number of
      studies indicated that the PD-1(programmed cell death-1)/PD-Ls signal pathway
      played an important role in regulating the immunopathogenesis of brain after
      injured. The relevant knowledges about PD-1/PD-Ls signal pathway, and potential
      effect with immune cells, cerebral ischemia, brain tumors and multiple sclerosis
      were reviewed in this paper. CONCLUSION: PD-1/PD-Ls played important roles in
      maintaining immunity balance and the development and prognosis of CNS diseases,
      but the specific mechanism was still not well understood.

PMID- 27889995
TI  - The Roles of the Unique Prolyl Isomerase Pin1 in Cancer-Related Viral and
      Bacterial Infections.
AB  - Infection is the process of pathogen invasion, as well as the host reaction to
      the foreign agents. Proline-directed phosphorylation is a major regulatory
      mechanism that regulates the function of fundamental proteins involved in
      infection and infection-induced cancer. Recently, the identification of the
      phosphorylation-dependent prolyl isomerase Pin1 has uncovered a unique regulatory
      signaling mechanism controlling protein conformation and function after
      phosphorylation. Pin1 is the only proline isomerase that specifically recognizes
      certain Pro-directed Ser/Thr phosphorylation motifs. Pin1 has emerged as a major
      regulator of cancerrelated viral and bacterial infections notably via activating
      Toll-like receptor signaling and NF-kappaB pathways. This paper will specifically
      review recent findings on the role of Pin1 in cancer-related viral and bacterial
      infections and also discuss newly discovered Pin1 inhibitors as promising drugs
      for the prevention and treatment of viral and bacterial infections and associated
      tumorigenesis.

PMID- 27889996
TI  - Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST)
      and Microsatellite Instability in Patients with Colorectal Cancer and Its
      Clinical Features.
AB  - PURPOSE: Recently, a different type of microsatellite instability (MSI)
      instability designated 'elevated microsatellite alterations at selected
      tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its
      clinical implications remain unclear. We aimed to determine the relationships
      among EMAST, MSI and clinicopathologic characteristics, including oncologic
      outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100
      sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242,
      D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status.
      Immunohistochemical detection of hMSH3, c-erbB2, EGFR and thymidylate synthase
      was performed. Clinical characteristics and prognostic relevance were assessed.
      RESULTS: We identified 22 EMAST-positive tumors (22.0%) and 32 MSI-high (MSI-H)
      tumors (32.0%). EMAST was more frequent in colon cancer than rectal cancer
      (p=0.033), and associated with MSI-H phenotype (p<0.001), low expression of hMSH3
      (p=0.004), and overexpression of thymidylate synthase (p=0.006). Among the 38 MSI
      L tumors, only one (4.5%) showed EMAST. Long-term oncologic results in terms of
      overall and disease-free survival were similar between EMAST and non-EMAST
      tumors. CONCLUSION: EMAST is more closely related to MSI-H than MSI-L or MSS
      status. The clinical and molecular characteristics of EMAST were distinct in
      terms of tumor location, thymidylate synthase expression, MSI status and hMSH3
      expression. Our preliminary findings support the utility of EMAST as a new
      potential classifier in CRC.

PMID- 27889997
TI  - Acute Cystitis Caused by Commensal Neisseria oralis: A Case Report and Review of
      the Literature.
AB  - BACKGROUND: Neisseria are usually harmless inhabitants of otherwise asymptomatic
      persons' upper respiratory mucosal surfaces. METHOD: It is, therefore, expected
      that a disturbance in the physiology leads to nongonococcal, non-meningococcal
      Neisseria becoming pathogenic. RESULT: We report the case of a diabetic man who
      initially presented with nonspecific symptoms and was later found to have
      cystitis caused by N. oralis. CONCLUSION: We also review the pertinent literature
      and discuss available evidence on pathophysiological mechanisms of infection with
      such commensal bacteria.

PMID- 27889998
TI  - MicroRNAs and Aging: Biomarkers or Therapeutic Targets?
AB  - Understanding the molecular mechanism of aging is of utmost importance to the
      scientific communities. To date, various theories have been proposed and many of
      them were evaluated as potential targets in the battle against aging. MicroRNAs,
      the universal gene expression regulators, were found to be associated with the
      aging process as many of them have been linked to biological process associated
      with cellular deterioration. In this short report, we briefly review the
      contribution of miRNAs to the aging process and offer an opinion as to how the
      knowledge of the role of these molecules in aging can be utilized.

PMID- 27889999
TI  - Comprehensive Assessment of Compliance with Antimuscarinic Drug Treatment in the
      Case of Urge Urinary Incontinence of Older Patients.
AB  - AIM: To investigate the heterogeneous factors affecting the stability of patients
      older than 60 years in the UI treatment with Antimuscarinics. BACKGROUND: The
      prevalence of Urge Incontinence (UI) in older persons reaches 29.3%. The symptoms
      of urinary incontinence in older people reduce the health related life quality.
      MATERIALS AND METHODS: In 1257 patients over 60 years (857 (68.2%) women -
      average age 67.8, 400 (31.8%) men - 71.4), who received AM for one year,
      demographic, socio-economic and health parameters were studied. OABq-SF
      questionnaires, MOS SF-36, urination diaries, uroflowmetry, income information
      from the tax offices and outpatient records were used. RESULT: The compliance to
      AM treatment within 6 months was retained in 44.2%, and within the year - 26.8%
      of older patients. At least 40% of the total number of patients refused to
      continue the treatment for medical reasons. The persons taking Solifenacin (p<=
      0.01), Trospium (p<= 0.05), or Darifenacin (p<= 0.05), suffering from severe UI
      symptoms (p<= 0.01), and experiencing minor side effects (p<= 0.01), well
      informed about UI treatment methods (p<= 0.01) prevailed among the treatment
      compliant patients. At least 20.4% of the patients discontinued their treatment
      due to economic reasons. The persons with significantly larger annual income (p<=
      0.05) and annual medical cost (p<= 0.01) prevailed among the treatment compliant
      patients. About 12.2% of the patients stopped their treatment for reasons related
      to the social background and psychological status. CONCLUSION: In this
      experiment, we found that AM treatment compliance in older patients, in addition
      to medical parameters and health conditions, is largely affected by the economic
      as well as social, demographic and psychological factors. The study results can
      be claimed by practitioners involved in correcting UI symptoms in older people.

PMID- 27890001
TI  - Editorial: Inflammasome Complex in Health and Disease: New Pharmacological
      Perspectives.

PMID- 27890000
TI  - Reproductive Toxicity of T Cells in Early Life: Abnormal Immune Development and
      Postnatal Diseases.
AB  - Immunity is a balanced status with adequate biological defenses to recognize and
      fight "non-self", as well as adequate tolerance to recognize "self". To maintain
      this immune homeostasis, a well-organized T cell immune network is required,
      which in part depends on the well-controlled development of alternative effector
      T cells, with different cytokine repertoires. Recent researches have pointed that
      developing fetal T cells network is a remarkably sensitive toxicological target
      for adverse factors in early life. Epidemiological and experimental studies
      showed an inseparable relationship between T cell developmental toxicity and
      immune diseases in adults. Considering that the inflammatory and immune disorders
      have become a growing health problem worldwide, increasing attention is now being
      paid to the T cell developmental toxicity. We propose that adverse factors may
      have programming effects on the crucial functions of immune system during early
      life which is critical for fetal T cell development and the establishment of the
      distinct T cell repertoires balance. The permanently disturbed intrathymic or
      peripheral T cell development may in turn lead to the immune disorders in later
      life. In this manuscript, we reviewed how adverse factors affected T cell
      development in early-life with the consequence of the immune dysfunction and
      immune diseases, and further elucidate the mechanisms. These mechanisms will be
      helpful in prevention and treatment of the increased prevalence of immune
      diseases by interfering those pathways.

PMID- 27890002
TI  - Photosensitizers for Photodynamic Therapy: Photochemistry in the Service of
      Oncology.
AB  - The combined use of a photosensitizing agent, light and dioxygen for the
      treatment of diseases has become known as photodynamic therapy (PDT) and was
      first discovered more than one hundred years ago. Over the years, PDT has proven
      its potential for the treatment of malignant and non-malignant lesions in
      addition to classical cancer therapy in numerous clinical studies, but
      application as a routine method is still limited. In this review, the development
      of modern PDT since the beginning of the twentieth century is briefly portrayed.
      The underlying mechanisms of phototoxicity are explained, and the requirements
      for ideal photosensitizers (PS) are underlined. Selected PS are introduced and
      examples of some of the many attempts made at the optimization of PDT by
      developing new PS with improved chemical and phototoxic properties, are reviewed.
      Promising 3rd generation PS are introduced and newer approaches to increasing
      tumor selectivity and efficacy of PDT, such as with nanoparticles, are discussed.

PMID- 27890003
TI  - Biofilm-mediated Antibiotic-resistant Oral Bacterial Infections: Mechanism and
      Combat Strategies.
AB  - Oral diseases like dental caries and periodontal disease are directly associated
      with the capability of bacteria to form biofilm. Periodontal diseases have been
      associated to anaerobic Gram-negative bacteria forming a subgingival plaque
      (Porphyromonas gingivalis, Actinobacillus, Prevotella and Fusobacterium). Biofilm
      is a complex bacterial community that is highly resistant to antibiotics and
      human immunity. Biofilm communities are the causative agents of biological
      developments such as dental caries, periodontitis, peri-implantitis and causing
      periodontal tissue breakdown. The review recapitulates the latest advancements in
      treatment of clinical biofilm infections and scientific investigations, while
      these novel anti-biofilm strategies are still in nascent phases of development,
      efforts dedicated to these technologies could ultimately lead to anti-biofilm
      therapies that are superior to the current antibiotic treatment. This paper
      provides a review of the literature focusing on the studies on biofilm in the
      oral cavity, formation of dental plaque biofilm, drug resistance of bacterial
      biofilm and the antibiofilm approaches as biofilm preventive agents in dentistry,
      and their mechanism of biofilm inhibition.

PMID- 27890004
TI  - Lactic Acid Bacteria as Cell Factories for the Generation of Bioactive Peptides.
AB  - There is a growing interest in the incorporation of functional foods in the daily
      diet to achieve health promotion and disease risk reduction. Numerous studies
      have focused on the production of biologically active peptides as nutraceuticals
      and functional food ingredients due to their health benefits. These short
      peptides, displaying antihypertensive, antioxidant, mineral binding,
      immunomodulatory and antimicrobial activities are hidden in a latent state within
      the primary sequences of food proteins requiring enzymatic proteolysis for their
      release. While microbial fermentation is one of the major and economically most
      convenient processes used to generate bioactive peptides, lactic acid bacteria
      (LAB) are widely used as starter cultures for the production of diverse fermented
      foods. This article reviews the current knowledge on LAB as cell factories for
      the production of bioactive peptides from a variety of food protein sources.
      These microorganisms depend on a complex proteolytic system to ensure successful
      fermentation processes. In the dairy industry, LAB containing cell envelope
      associated proteinases (CEPs) are employed as biocatalysts for the first step of
      casein breakdown releasing bioactive peptides during milk fermentation. A better
      understanding of the functionality and regulation of the proteolytic system of
      LAB opens up future opportunities for the production of novel food-derived
      compounds with potential health-promoting properties.

PMID- 27890005
TI  - Mechanism-Based Inhibitors from Phytomedicine: Risks of Hepatotoxicity and their
      Potential Hepatotoxic Substructures.
AB  - BACKGROUND: The adverse drug reactions and poisoning events associated with the
      use of herbal medicines, especially the potential damaging effects of them on the
      liver organs, have increasingly been reported worldwide. Some herbal ingredients
      in medicinal plants carry the risk of herb-induced liver injury with a severe or
      potentially lethal clinical course, but the hepatotoxicity mechanisms and risk
      factors of them are not well characterized until now. Xenobiotics are converted
      by cytochrome P450 enzymes into highly reactive metabolites that covalently bind
      to the catalytic site of the enzyme itself, subsequently causing mechanism-based
      inhibition (MBI). Compared to reversible inhibition, MBI more frequently results
      in unfavorable acute and/or immune system-mediated idiosyncratic toxicities and
      drug/herb-drug interactions (DDI/HDIs). METHODS: We searched PubMed databases
      (1980-2015) for articles published in the English language to identify
      publications on mechanism-based inhibitors from phytomedicine and herbal
      ingredients hepatotoxicity. RESULTS: 43 mechanism-based inhibitors from
      phytomedicine were summarized. Twelve of these inhibitors could cause
      hepatotoxicity, whereas the rest have no related reports. Among them, six
      hepatotoxic mechanism-based inhibitors are proven to induce hepatotoxicity via
      their reactive metabolites (RMs). The possible mechanism for this hepatotoxicity
      is that RMs react with cellular components such as proteins, DNA, and membranes,
      resulting in ROS overproduction, respiratory chain dysfunction, and cell stress.
      Moreover, the amine and furan heterocycle groups might be the most potential
      substructures in mechanism-based inhibitors which can cause hepatotoxicity.
      CONCLUSION: These results suggest that when mechanism-based inhibitors from
      phytomedicine containing amine or furan heterocycle substructures are used alone
      or with other drugs, in vivo hepatotoxicity screening or its clinical
      implications for herb-drug interactions are needed to attention.

PMID- 27890006
TI  - Recent Updates on the Systemic and Local Safety of Intranasal Steroids.
AB  - BACKGROUND: Allergic rhinitis is a global health problem, and its prevalence rate
      and socioeconomic burden continue to increase. Intranasal steroid (INS) is the
      first treatment choice in the majority of patients, because of its ability to
      effectively control allergic symptoms. However, patients and clinicians are
      concerned about the potential adverse effects of prolonged INS use. METHODS: We
      performed to review for evaluating systemic and local safety of INS use, by
      searching MEDLINE, EMBASE, and Cochrane Library database for identification of
      relevant articles. RESULTS: In the present study, the systemic bioavailabilities
      of several commercially available INSs were researched, and then systemic
      safeties were reviewed with focus on suppression of the hypothalamus-pituitary
      adrenal axis and their effects on pediatric growth. In addition, local adverse
      effects, such as, epistaxis and nasal septal perforation, were investigated.
      Finally, the authors proposed some techniques in order to avoid these
      complications. CONCLUSION: INSs offer a safe, effective means of treating
      allergic rhinitis in the short- and long-term with no or minimal adverse systemic
      and local effects.

PMID- 27890007
TI  - A Current Perspective on the Inhibition of Cholinesterase by Natural and
      Synthetic Inhibitors.
AB  - Majority of the observed cognitive and behavioral changes in Alzheimer's disease
      are postulated to be due to the deficiencies in cholinergic pathways of the
      brain. Enhancement of cholinergic transmission may thus stimulate the cholinergic
      receptors or prolong the availability of acetylcholine in synaptic cleft and
      hence improve the Alzheimer's disease associated symptoms. Of these two, the
      inhibition of cholinesterases (Acetylcholinesterase and Butyrylcholinesterase) by
      cholinesterase inhibitors is suggested to be a promising strategy. In this
      regard, various agents both natural and non-natural have been evaluated for the
      inhibition of cholinesterases. Phytochemical studies of some of the medicinal
      plants have shown the presence of many valuable compounds that show a wide range
      of pharmacological activity against cholinesterase enzymes. Interestingly, a good
      number of potent synthetic inhibitors of cholinesterase enzymes reported so far
      are natural-product based. This article aims to provide a comprehensive overview
      of both natural and synthetic cholinesterase inhibitors reported so far.
      Presenting a comparative overview of synthetic and natural cholinesterase
      inhibitors may provide some leads for the synthesis of new cholinesterase
      inhibitors from medicinal plants. Structural activity relationship of the active
      cholinesterase inhibitors is also discussed with some insights from simulation
      studies. Insights for possible future research have also been highlighted.

PMID- 27890009
TI  - A Feature-Free 30-Disease Pathological Brain Detection System by Linear
      Regression Classifier.
AB  - AIM: Alzheimer's disease patients are increasing rapidly every year. Scholars
      tend to use computer vision methods to develop automatic diagnosis system.
      (Background) In 2015, Gorji et al. proposed a novel method using pseudo Zernike
      moment. They tested four classifiers: learning vector quantization neural
      network, pattern recognition neural network trained by Levenberg-Marquardt, by
      resilient backpropagation, and by scaled conjugate gradient. METHOD: This study
      presents an improved method by introducing a relatively new classifier-linear
      regression classification. Our method selects one axial slice from 3D brain
      image, and employed pseudo Zernike moment with maximum order of 15 to extract 256
      features from each image. Finally, linear regression classification was harnessed
      as the classifier. RESULTS: The proposed approach obtains an accuracy of 97.51%,
      a sensitivity of 96.71%, and a specificity of 97.73%. CONCLUSION: Our method
      performs better than Gorji's approach and five other state-of-the-art approaches.
      Therefore, it can be used to detect Alzheimer's disease.

PMID- 27890008
TI  - Functional Connectivity Analysis of Brain Default Mode Networks Using Hamiltonian
      Path.
AB  - The aim of this study is to introduce Hamiltonian path to analyze functional
      connectivity of brain default mode networks (DMNs). Firstly, the brain DMNs in
      resting state are constructed with the employment of functional Magnetic
      Resonance Imaging (fMRI) data. Then, the Dijkstra algorithm is used to calculate
      the shortest path length of the node which represents each brain region, and the
      Hamiltonian path of the default network is solved through the improved adaptive
      ant colony algorithm. Finally, complex network analysis methods are introduced to
      discuss the node and network properties of brain functional connectivity in both
      normal subjects and stroke patients. The experimental result demonstrated that
      there are some significant differences in the properties of the DMNs between
      stroke patients and normal subjects, especially the length of Hamiltonian path.
      It also verifies the effectiveness on studying the functional connectivity of the
      brain DMNs by applying the proposed method of Hamiltonian path.

PMID- 27890010
TI  - Biological Function and Mechanism of Bone Marrow Mesenchymal Stem Cells-packed
      Poly (3,4-ethylenedioxythiophene) (PEDOT) Scaffolds for Peripheral Nerve Injury:
      The Involvement of miR-21-Notch Signaling Pathway.
AB  - Ununited peripheral nerves represent attractive site for connectivity with
      neuroprostheses because their predictable internal topography allows precise
      sorting of motor and sensory signals. Also transplantation of bone marrow
      mesenchymal stem cells (BMSCs) is increasingly recognized as an effective method
      of restore the peripheral nervous system injury due to its neuron-directed
      differentiation potential. This study was to evaluate the in vivo performance of
      BMSCs-packed Poly(3,4-ethylenedioxythiophene) (PEDOT) scaffolds across a critical
      nerve conduction gap and examine the potential mechanism by which BMSCs-packed
      PEDOT scaffolds mediate peripheral nerve regeneration in rat model of recurrent
      laryngeal nerve (RLN) deletion. In this study, rat models of 8 mm-RLN deletion
      were randomly divided into three groups and respectively received transplantation
      of autologous nerve or PEDOT scaffolds or BMSCspacked PEDOT scaffolds. After
      transplantation, neurological function was assessed by laryngeal
      electromyography. BMSCs-directed neuron differentiation was induced and confirmed
      by the upregulation of 6 nerve cell markers. Expression level of miRs, Notch
      signals and 6 nerve cell markers in nerve grafts or cells were determined by
      quantitative real-time PCR or western blot analysis. The results showed that
      BMSCs-packed PEDOT scaffolds transplantation significantly improved neurological
      function compared with PEDOT scaffolds alone. Regenerative nerve of BMSCs-packed
      PEDOT scaffolds showed higher expression level of miR-21 and Notch signals (Hes-1
      and Notch intracellular domain (NICD)) than PEDOT alone. We found that the
      expression levels of miR-21, Hes-1 and NICD are increased with timecourse of
      neuron-directed differentiation stimulating of BMSCs. Meanwhile, both miR-21
      overexpression and Notch pathway activation promote the expression of 6 nerve
      cell markers in BMSCs-directed neuron, whereas the inactivation of Notch pathway
      abrogates miR-21-inudced upregulation of 6 nerve cell markers. Moreover, knock
      down of miR-21 suppresses the pro-neural restoration action of BMSCs-packed PEDOT
      scaffolds. In summary, our data suggested that BMSCs-packed PEDOT effectively
      repairs recurrent laryngeal nerve injury and the potential mechanism is miR-21-
      mediated Notch signal activation.

PMID- 27890011
TI  - MicroRNA MiR-130b promotes wear particle-induced osteolysis via down regulating
      frizzled-related protein (FRZB).
AB  - Periprosthetic osteolysis induced by wear particles can lead to aseptic
      loosening, one main reason of arthroplasty failure. However, the role of microRNA
      130b (miR-130b) in particle-induced osteolysis (PIO) has not been explored yet.
      In this study, PIO models were established in C57BL/J6 mice via the implantation
      of Co-Cr-Mo alloy particles, and evaluated by detecting tartrate-resistant acid
      phosphatase (TRAP) activity and bone resorption in the calvaria. Mouse
      preosteoblast MC3T3-E1 cells were cultured to receive particle stimulation in
      vitro. Real time PCR and western blotting were performed to determine the
      expression levels of miR-130b and frizzled-related protein (FRZB), one potential
      target of miR-130b. Results showed upregulated miR-130b and downregulated FRZB in
      both PIO mice with remarkable osteolysis and particle-treated MC3T3-E1 cells
      showing inhibited proliferation and differentiation assayed by bromodeoxy urodine
      (BrdU) incorporation and alkaline phosphatase (ALP) activity respectively.
      Functional studies were conducted by transfection of miR-130b inhibitor in vitro
      or the injections of miR-130b inhibitor or small interfering RNA (siRNA)
      targeting FRZB in vivo. Interestingly, particle-induced inhibition on cell
      proliferation, differentiation and FRZB expression were all reversed by miR-130b
      silence. Luciferase report assays demonstrated that miR-130b indeed negatively
      regulated FRZB expression by targeting, while FRZB could reverse the opposed
      effect of miR-130b silence on PIO development. Therefore, the upregulated miR
      130b in PIO models could act as one key regulator of PIO development, partly due
      to its negative regulation on FRZB.

PMID- 27890012
TI  - The Biology of beta-D-mannuronic acid (M2000) on Human Dendritic Cell Based on
      MicroRNA-155 and MicroRNA-221.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of beta-Dmannuronic
      acid (M2000) on related miRNAs to dendritic cells (DCs) differentiation. DC-based
      immunosuppressive drugs can suppress the progression of autoimmune diseases,
      however, their notable side effects in increasing the risk of infectious diseases
      and cancers should be considered. The beta-D-mannuronic acid, as a novel non
      steroidal anti-inflammatory agent, has been tested in various experimental
      models. METHOD: The effect of M2000 on expression of miRNA-155 and miRNA-221 was
      examined. To investigate how M2000 affects differentiation of human dendritic DCs
      in a defined inflammatory environment, human peripheral blood mononuclear cells
      were isolated from healthy blood and the monocytes were purified using anti-CD14
      microbeads. The so isolated monocytes were subsequently incubated in the presence
      of M2000 in two different doses (3 and 6 mMol/well) adding granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and interleukin-4 for inducing monocytes to
      immature DC and lipopolysaccharide for running DC differentiation. The expression
      of miRNA-155 and miRNA-221 were examined with Real Time PCR. RESULTS: The results
      demonstrate that M2000 has no significant side effect on expression of miR-155
      and miR-221 in both immature DC and mature DC process in vitro. CONCLUSION: Our
      findings show that beta-D-mannuronic acid is a safe agent which has no adverse
      effect on regulatory miRNA-155 and miRNA-221 in dendritic cells.

PMID- 27890013
TI  - In-Silico Characterization of a Hypothetical Protein, Rv1288 of Mycobacterium
      tuberculosis Containing an Esterase Signature and an Uncommon LytE Domain.
AB  - BACKGROUND: Death toll due to tuberculosis is still rising day by day. Whole
      genome sequence of Mycobacterium tuberculosis has provided a platform to conduct
      research in order to identify the probable drug target. OBJECTIVES: Out of 4000
      gene products of M. tuberculosis, approximately 40% of proteins are annotated as
      hypothetical. Identifying and characterizing these proteins could provide a new
      prescriptive for developing new TB drugs. Rv1288, a protein of M. tuberculosis
      H37Rv has been annotated as a hypothetical protein in database. Attempt has been
      made to assign a meaningful role to rv1288 gene product in M. tuberculosis life
      cycle. METHODS: A homology 3D structure of both domains was separately generated
      and assigned as Rv1288LytE and Rv1288est. Molecular simulation of Rv1288est was
      carried out for proper structure analysis. To further confirm the predictive role
      of Rv1288 in mycobacterium life cycle, molecular docking was performed. N-acetyl
      glucosamine, a major constituent of cell wall was docked with LytE domain,
      whereas, esterase domain was docked with lipolytic substrate, pNP-ester
      derivatives and inhibitors THL/PMSF. RESULTS: In-silico analysis revealed that
      Rv1288 is a two domain protein, an N-terminal LytE domain containing three
      consecutive LysM motifs and a C-terminal esterase domain of esterase D family.
      LytE domain has the property to bind N-acetyl glucosamine moieties of
      peptidoglycan, a major component of cell wall. Detailed in-silico sequence
      analysis revealed that this LytE domain may help in positioning the esterase
      domain to the cell wall of mycobacterium. Esterase domain comprised a
      tetrapeptide motif HGGG, a pentapeptide sequence motif GxSxG and conserved amino
      acid residues Ser-141, Asp-238 and His-272 which constitute a catalytic triad
      characteristic of other hormone sensitive lipases/ esterases. Docking studies
      suggested that THL and PMSF could be the potent inhibitors for Rv1288 protein.
      CONCLUSION: In the present investigation, we bioinformatically confirmed that
      Rv1288 is most likely a LytE domain containing lipolytic enzyme showing
      similarity to hormone sensitive lipases/esterases.

PMID- 27890014
TI  - Chagas' heart disease: gender differences in myocardial damage assessed by
      cardiovascular magnetic resonance.
AB  - BACKGROUND: Since a male-related higher cardiovascular morbidity and mortality in
      patients with Chagas' heart disease has been reported, we aimed to investigate
      gender differences in myocardial damage assessed by cardiovascular magnetic
      resonance (CMR). METHODS AND RESULTS: Retrospectively, 62 seropositive Chagas'
      heart disease patients referred to CMR (1.5 T) and with low probability of having
      significant coronary artery disease were included in this analysis. Amongst both
      sexes, there was a strong negative correlation between LV ejection fraction and
      myocardial fibrosis (male r = 0.64, female r = 0.73, both P < 0.001), with males
      showing significantly greater myocardial fibrosis (P = 0.002) and lower LV
      ejection fraction (P < 0.001) than females. After adjustment for potential
      confounders, gender remained associated with myocardial dysfunction, and 53% of
      the effect was mediated by myocardial fibrosis (P for mediation = 0.004). Also,
      the transmural pattern was more prevalent among male patients (23.7 vs. 9.9%, P <
      0.001) as well as the myocardial heterogeneity or gray zone (2.2 vs. 1.3 g, P =
      0.003). CONCLUSIONS: We observed gender-related differences in myocardial damage
      assessed by CMR in patients with Chagas' heart disease. As myocardial fibrosis
      and myocardial dysfunction are associated to cardiovascular outcomes, our
      findings might help to understand the poorer prognosis observed in males in
      Chagas' disease.

PMID- 27890015
TI  - The involvement of regulatory non-coding RNAs in sepsis: a systematic review.
AB  - BACKGROUND: Sepsis coincides with altered gene expression in different tissues.
      Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and
      circular RNAs are important molecules involved in the crosstalk with various
      pathways pertinent to innate immunity, mitochondrial functions, and apoptosis.
      METHODS: We searched articles indexed in PubMed (MEDLINE), EMBASE and Europe
      PubMed Central databases using the Medical Subject Heading (MeSH) or
      Title/Abstract words ("microRNA", "long non-coding RNA", "circular RNA", "sepsis"
      and/or "septic shock") from inception to Sep 2016. Studies investigating the role
      of host-derived microRNA, long non-coding RNA, and circular RNA in the
      pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data
      were extracted in terms of the role of non-coding RNAs in pathogenesis, and their
      applicability for use as biomarkers or therapeutics in sepsis. Two independent
      researchers assessed the quality of studies using a modified guideline from the
      Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool
      based on the Cochrane Collaboration Risk of Bias tool. RESULTS: Observational
      studies revealed dysregulation of non-coding RNAs in septic patients.
      Experimental studies confirmed their crosstalk with JNK/NF-kappaB and other
      cellular pathways pertinent to innate immunity, mitochondrial function, and
      apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average
      score of 4.55). This suggests a moderate risk of bias. Of the 10 articles
      investigating non-coding RNAs as biomarkers, none of them included a validation
      cohort. Selective reporting of sensitivity, specificity, and receiver operating
      curve was common. CONCLUSIONS: Although non-coding RNAs appear to be good
      candidates as biomarkers and therapeutics for sepsis, their differential
      expression across tissues complicated the process. Further investigation on organ
      specific delivery of these regulatory molecules may be useful.

PMID- 27890016
TI  - The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review
      of the pathophysiology.
AB  - Extracorporeal membrane oxygenation (ECMO) is a technology capable of providing
      short-term mechanical support to the heart, lungs or both. Over the last decade,
      the number of centres offering ECMO has grown rapidly. At the same time, the
      indications for its use have also been broadened. In part, this trend has been
      supported by advances in circuit design and in cannulation techniques. Despite
      the widespread adoption of extracorporeal life support techniques, the use of
      ECMO remains associated with significant morbidity and mortality. A complication
      witnessed during ECMO is the inflammatory response to extracorporeal circulation.
      This reaction shares similarities with the systemic inflammatory response
      syndrome (SIRS) and has been well-documented in relation to cardiopulmonary
      bypass. The exposure of a patient's blood to the non-endothelialised surface of
      the ECMO circuit results in the widespread activation of the innate immune
      system; if unchecked this may result in inflammation and organ injury. Here, we
      review the pathophysiology of the inflammatory response to ECMO, highlighting the
      complex interactions between arms of the innate immune response, the endothelium
      and coagulation. An understanding of the processes involved may guide the design
      of therapies and strategies aimed at ameliorating inflammation during ECMO.
      Likewise, an appreciation of the potentially deleterious inflammatory effects of
      ECMO may assist those weighing the risks and benefits of therapy.

PMID- 27890018
TI  - Compensation of Emergency Medical Technician (EMT)-Basics and Paramedics.
AB  - OBJECTIVES: The objective of this paper is to identify factors associated with
      compensation for Emergency Medical Technician (EMT)-Basics and Paramedics and
      assess whether these associations have changed over the period 1999-2008.
      METHODS: Data obtained from the Longitudinal EMT Attributes and Demographic Study
      (LEADS) surveys, a mail survey of a random, stratified sample of nationally
      certified EMT-Basics and Paramedics, were analyzed. For the 1999-2003 period,
      analyses included all respondents providing Emergency Medical Services (EMS).
      With the addition of a survey in 2004 about volunteers, it was possible to
      exclude volunteers from these analyses. RESULTS: Over 60% of EMT-Basics reported
      being either compensated or noncompensated volunteers in the 2004-2008 period.
      This was substantially and significantly greater than the proportion of EMT
      Paramedic volunteers (<25%). The EMT-Paramedics earned significantly more than
      EMT-Basics, with differentials of $11,000-$18,000 over the course of the study.
      The major source of earnings disparity was type of organization: respondents
      employed by fire-based EMS agencies reported significantly higher earnings than
      other respondents, at both the EMT-Basic and EMT-Paramedic levels. Males also
      earned significantly more than females, with annual earnings differentials
      ranging from $7,000 to $15,000. CONCLUSIONS: There are a number of factors
      associated with compensation disparities within the EMS profession. These include
      type of service (ie, fire-based vs. other types of agencies) and gender. The
      reasons for these disparities warrant further investigation. Studnek JR .
      Compensation of Emergency Medical Technician (EMT)-Basics and Paramedics. Prehosp
      Disaster Med. 2016;31(Suppl. 1):s87-s95.

PMID- 27890017
TI  - Extremely low nucleotide diversity in the X-linked region of papaya caused by a
      strong selective sweep.
AB  - BACKGROUND: The papaya Y-linked region showed clear population structure,
      resulting in the detection of the ancestral male population that domesticated
      hermaphrodite papayas were selected from. The same populations were used to study
      nucleotide diversity and population structure in the X-linked region. RESULTS:
      Diversity is very low for all genes in the X-linked region in the wild dioecious
      population, with nucleotide diversity pi syn = 0.00017, tenfold lower than the
      autosomal region (pi syn = 0.0017) and 12-fold lower than the Y-linked region (pi
      syn = 0.0021). Analysis of the X-linked sequences shows an undivided population,
      suggesting a geographically wide diversity-reducing event, whereas two
      subpopulations were observed in the autosomes separating gynodioecy and dioecy
      and three subpopulations in the Y-linked region separating three male
      populations. The extremely low diversity in the papaya X-linked region was
      probably caused by a recent, strong selective sweep before domestication,
      involving either the spread of a recessive mutation in an X-linked gene that is
      beneficial to males or a partially dominant mutation that benefitted females or
      both sexes. Nucleotide diversity in the domesticated X samples is about half that
      in the wild Xs, probably due to the bottleneck when hermaphrodites were selected
      during domestication. CONCLUSIONS: The extreme low nucleotide diversity in the
      papaya X-linked region is much greater than observed in humans, great apes, and
      the neo-X chromosome of Drosophila miranda, which show the expected pattern of Y
      linked genes < X-linked genes < autosomal genes; papaya shows an unprecedented
      pattern of X-linked genes < autosomal genes < Y-linked genes.

PMID- 27890019
TI  - Vitamin A deficiency and determinants of vitamin A status in Bangladeshi children
      and women: findings of a national survey.
AB  - OBJECTIVE: Using data from the national micronutrients survey 2011-2012, the
      present study explored the status of subclinical vitamin A nutrition and the
      underlying determinants in the Bangladeshi population. DESIGN: A nationwide cross
      sectional study. Settings The survey covered 150 clusters; fifty in each of
      rural, urban and slum strata. SUBJECTS: Three population groups: (i) pre-school
      age children (6-59 months; PSAC); (ii) school age children (6-14 years; SAC); and
      (iii) non-pregnant non-lactating women (15-49 years; NPNLW). RESULTS: National
      prevalence of subclinical vitamin A deficiency was 20.5, 20.8 and 5.3 % in PSAC,
      SAC and NPNLW, respectively. Slum populations had higher prevalence compared with
      urban (PSAC: 38.1 v. 21.2 %, P0.05 for differences in beta between <3 months v. 3
      6 months, 6-9 months and 9-12 months). CONCLUSIONS: Prevalence of subclinical
      vitamin A deficiency was high in children in Bangladesh. Intakes of animal-source
      foods and leafy vegetables were associated with higher and lower retinol status,
      respectively. Increased food diversity through animal-source foods is required.

PMID- 27890020
TI  - Choice architecture to promote fruit and vegetable purchases by families
      participating in the Special Supplemental Program for Women, Infants, and
      Children (WIC): randomized corner store pilot study.
AB  - OBJECTIVE: To conduct a pilot study to determine if improving the visibility and
      quality of fresh produce (choice architecture) in corner stores would increase
      fruit/vegetable purchases by families participating in the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC). DESIGN: Six stores were
      randomly assigned to choice architecture intervention or control. Store-level WIC
      sales data were provided by the state. Primary outcomes were WIC fruit/vegetable
      voucher and non-fruit/vegetable voucher sales, comparing trends from baseline
      (December 2012-October 2013) with the five-month intervention period (December
      2013-April 2014). Secondary outcomes were differences in customer self-reported
      fruit/vegetable purchases between baseline and end of the intervention. SETTING:
      Chelsea, MA, USA, a low-income urban community. SUBJECTS: Adult customers (n 575)
      completing store exit interviews. RESULTS: During baseline, WIC fruit/vegetable
      and non-fruit/vegetable sales decreased in both intervention and control stores
      by $US 16/month. During the intervention period, WIC fruit/vegetable sales
      increased in intervention stores by $US 40/month but decreased in control stores
      by $US 23/month (difference in trends: $US 63/month; 95 % CI 4, 121 $US/month;
      P=0.036); WIC non-fruit/vegetable sales were not different (P=0.45). Comparing
      baseline and intervention-period exit interview responses by customers
      participating in WIC (n 134), intervention store customers reported increased
      fruit/vegetable purchases compared with control store customers (18 v. -2 %), but
      this did not achieve statistical significance (P=0.11). CONCLUSIONS: Placement of
      fruits/vegetables near the front of corner stores increased purchase of produce
      by customers using WIC. New policies that incentivize stores to stock and
      prominently display good-quality produce could promote healthier food choices of
      low-income families.

PMID- 27890021
TI  - The relationship between food insecurity and overweight/obesity differs by
      birthplace and length of US residence.
AB  - OBJECTIVE: To examine whether the cross-sectional association between food
      insecurity and overweight/obesity varied according to birthplace and length of
      residence in the USA among California women. DESIGN: Using cross-sectional,
      population-based data from the California Women's Health Survey (CWHS) 2009-2012,
      we examined whether the association between food insecurity and overweight or
      obesity varied by birthplace-length of US residence. SETTING: California, USA.
      SUBJECTS: Women (n 16 008) aged 18 years or older. RESULTS: Among US-born women,
      very low food security (prevalence ratio (PR)=1.21; 95 % CI 1.11, 1.31) and low
      food security (PR=1.19; 95 % CI 1.10, 1.28) were significantly associated with
      higher prevalence of overweight/obesity, after controlling for age, marital
      status, race/ethnicity, poverty and education. Among immigrant women who lived in
      the USA for 10 years or longer, very low food security was significantly
      associated with higher prevalence of overweight/obesity, after controlling for
      covariates (PR=1.16; 95 % CI 1.07, 1.27). Among immigrant women who had lived in
      the USA for less than 10 years, low and very low food security were not
      significantly associated with overweight/obesity, after controlling for
      covariates. CONCLUSIONS: Food insecurity may be an important pathway through
      which weight may increase with longer US residence among immigrant women. Public
      health programmes and policies should focus on increasing food security for all
      women, including immigrant women, as one strategy to reduce the prevalence of
      overweight/obesity.

PMID- 27890022
TI  - Continuous light after 2 months of long days stimulates ram testis volume and
      increases fertility in spring.
AB  - Seasonal reproduction is one of the major biotechnical and economic constraints
      of sheep production in temperate latitudes. Treatments using extra light followed
      by melatonin implants have been used satisfactorily in open barns, farms and
      artificial insemination centres to produce out-of-season sexual activity in rams.
      The aim of the present study is to explore the possibility of replacing melatonin
      implants with continuous light (LL), which was recently shown to increase LH
      secretion similar to melatonin and/or pinealectomy. Four experiments during 4
      consecutive years were conducted in 'Ile-de-France' rams. In each study, one
      group was systematically exposed to permanent light after a first photoperiodic
      treatment of 60 long days (LD-LL) during the winter and compared with various
      other control groups subjected either to a natural photoperiod or the classical
      LD-melatonin treatment. As expected, blood nocturnal melatonin secretion was
      suppressed by LL. In all four experiments, LL treatment produced a highly
      significant and robust increase in ram testicular volume in the spring compared
      with the testicular volume of control rams or of that of treated rams at the end
      of the LD. For the two experiments in which fertility was tested, fertility after
      hand-mating was significantly higher in LD-LL rams than in control rams (76% v.
      64%). Therefore, permanent light after an LD treatment may be an interesting
      alternative to LD-melatonin treatment to induce out-of-season sexual activity in
      rams.

PMID- 27890023
TI  - Progressive muscle relaxation as a supportive intervention for cancer patients
      undergoing chemotherapy: A systematic review.
AB  - BACKGROUND: Many cancer patients use a wide variety of techniques to improve
      their physical and mental well-being, including relaxation therapy and,
      specifically, Progressive Muscle Relaxation (PMR). However, there is no strong
      evidence that supports the efficacy of this technique. OBJECTIVE: Our aim was to
      review the evidence regarding the use of PMR as a supportive intervention for
      cancer patients undergoing chemotherapeutic treatment. METHOD: Six databases were
      electronically searched: AMED, the Cochrane Library, MEDLINE, PsychINFO, Scopus,
      and the Web of Science. After removing duplicates, 700 publications were screened
      and 57 identified as potentially relevant. The flow of information from record
      identification to study inclusion was conducted in accordance with the PRISMA
      statement. Original articles published in peer-reviewed journals that studied the
      use of PMR as an intervention, were randomized or included a matched control
      group, and that included patients receiving chemotherapy were included. Studies
      that combined PMR with other interventions were excluded. The methodological
      quality of included trials was assessed using the Jadad Scale and the CONSORT
      guidelines. RESULTS: A total of 5 of the 57 papers fulfilled the preset criteria
      and were included in our systematic review. Our findings indicate that PMR might
      improve comfort and reduce the anxiety levels and side effects caused by
      chemotherapy, with the exception of vomiting. Nonetheless, the quality of all the
      included studies was extremely low. SIGNIFICANCE OF RESULTS: There is evidence
      that PMR might have a few benefits for patients undergoing chemotherapy. Still,
      the small number of studies included and their poor quality limit the
      significance of our results. Despite the fact that pharmaceutical approaches for
      controlling side effects might be reaching their full potential and that there
      might be further usefulness for such integrative treatments as PMR, the need to
      run more high-quality trials testing the efficacy of this technique is warranted
      before suggesting its adoption as part of standard cancer care.

PMID- 27890024
TI  - End-of-life experiences and deathbed phenomena as reported by Brazilian
      healthcare professionals in different healthcare settings.
AB  - OBJECTIVE: The objectives of the present study were to describe and compare the
      characteristics and reports of end-of-life experiences (ELEs) by healthcare
      professionals at different institutions and to investigate the influence of
      religious beliefs on these reports. METHOD: A multicenter study was carried out
      in Brazil that included six nursing homes (NHs), a cancer hospital (ONC), and a
      palliative care (PC) unit. Sociodemographic data, ELE reports (Fenwick's
      questionnaire), religiosity (the Duke Religion Index), spirituality (the
      Spirituality Self-Rating Scale), and mental health (the DASS-21 questionnaire)
      were assessed. The analysis was performed using ANOVA and chi-square tests in
      order to compare ELE perceptions in these different settings. RESULTS: A total of
      133 healthcare professionals (46 ONC, 36 PC, and 51 NH) were interviewed, 70% of
      whom recounted at least one ELE report in the previous five years. The most
      common ELEs were "visions of dead relatives collecting the dying person" (88.2%),
      "a desire to mend family rifts" (84.9%), and "visions of dead relatives near the
      bed providing emotional comfort" (80.6%). Most healthcare professionals (70-80%)
      believed that these experiences had a spiritual significance and were not due to
      biological effects. Comparison among settings revealed that those working in the
      PC unit had more reports, a greater openness about the issue, and more interest
      in training. Individual religious beliefs had no influence on perception of ELEs.
      SIGNIFICANCE OF RESULTS: Our study revealed that ELE reports are not uncommon in
      clinical practice and seem to be little influenced by religious or spiritual
      beliefs. Although strongly reported in all settings, palliative care
      professionals tend to be more open to this issue and have a stronger perception
      of ELEs.

PMID- 27890025
TI  - Auguste Forestier's unbroken wanderlust.

PMID- 27890026
TI  - Electrostatic Capture Following Laser Microdissection for the Preparation of
      Homogeneous Biological Specimens.
AB  - There is an unmet need for researchers in life sciences and clinical pathology to
      obtain untainted target cells with very high accuracy, which are suitable for
      subsequent genome and protein analysis. In this paper, an electrostatic capture
      laser microdissection technology (ECM) is proposed and explained. Following
      microscopic identification and separation of target cells from the surrounding
      tissues using laser cutting, the ECM uses electrostatic forces to capture target
      cells. Validation experiments indicate that ECM can capture a wide assortment of
      contamination-free homogeneous samples, ranging from very tiny pieces of a few
      micrometers in diameter to large pieces with a surface area of over 40,000 um2.
      Evidence is also provided indicating that uncontaminated homogeneous tissue
      materials collected by ECM are suitable for further DNA and RNA analysis. This
      suggests that ECM capture causes little or no identifiable damage to the
      collected tissues. This technique has significant advantages compared with
      existing traditional capture methods, such as very low risk of biological sample
      damage and the fact that it can be applied to both upright and inverted
      microscopy. The latter allows for separating target cells in tissue culture. ECM
      usage provides a cost-effective alternative to more traditional laser capture
      microdissection techniques.

PMID- 27890027
TI  - A Longitudinal Description of Emergency Medical Services Professionals by
      Race/Ethnicity.
AB  - OBJECTIVE: The objective of this paper was to compare demographics, employment
      variables, satisfaction, and motivation for entering the field of Emergency
      Medical Services (EMS) between members of under-represented races/ethnicities and
      members of the majority group. METHODS: A cohort of nationally certified EMS
      professionals was followed for 10 years through annual surveys; however,
      race/ethnicity was only available for 9 years (2000-2008). Descriptive statistics
      and 95% confidence intervals (CIs) were calculated and significance was
      determined by lack of CI overlap. RESULTS: From 2000 through 2008, the range of
      proportions of nationally certified EMS professionals by race/ethnicity was as
      follows: whites: 83.5%-86.0%, Hispanics: 4.2%-5.9%, and African-Americans: 2.5%
      4.6%. There were no significant changes in the proportion of minority EMS
      professionals over the study period. Hispanics and African-Americans combined
      increased slightly from 6.7% of the population in 2000 to 9.9% in 2008. Likewise,
      the proportion of all under-represented races/ethnicities increased slightly from
      2000 (14.0%) to 2008 (16.5%). Females were under-represented in all years.
      Nationally certified African-Americans were significantly more likely to be
      certified at the Emergency Medical Technician (EMT)-Basic level (compared with
      the EMT-Paramedic level) than whites in all but one survey year. The proportion
      of Hispanics registered at the EMT-Basic level was significantly higher than
      whites in three survey years. Accordingly, a larger proportion of whites were
      nationally registered at the EMT-Paramedic level than both African-Americans and
      Hispanics. A significantly larger proportion of African-Americans reported
      working in urban communities (population >25,000) compared with whites for nine
      of the 10 survey years. Similarly, a significantly larger proportion of Hispanics
      worked in urban communities compared with whites in 2002 and from 2005 to 2008.
      For satisfaction measures, there were no consistent differences between
      races/ethnicities. Among factors for entering EMS, the proportion of whites who
      reported having a friend or family member in the field was significantly higher
      than African-Americans in all years and significantly higher than Hispanics in
      four of the nine years. CONCLUSION: The ethnic/racial diversity of the population
      of nationally certified EMS professionals is not representative of the population
      served and has not improved over the 2000-2008 period. Similar to other health
      care professions, Hispanics and African-Americans are under-represented in EMS
      compared with the US population. This study serves as a baseline to examine under
      represented populations in EMS. Crowe RP , Levine R , Eggerichs JJ , Bentley MA .
      A longitudinal description of Emergency Medical Services professionals by
      race/ethnicity. Prehosp Disaster Med. 2016;31(Suppl. 1):s30-s69.

PMID- 27890028
TI  - The newly revised interview for deteriorations in daily living activities in
      dementia (R-IDDD2): distinguishing initiative from performance at assessment.
AB  - BACKGROUND: Minimal evidence exists on the detailed deficits in complex
      instrumental activities of daily living (IADLs) in mild dementia. The aim of this
      study was twofold, to validate a revised questionnaire focusing measuring the
      initiative and performance of IADLs in mild dementia and to explore the
      relationship between individual IADLs and patient and carer well-being. METHODS:
      A total of 183 carers of people with mild dementia completed a further modified
      Revised Interview for Deterioration in Daily Living Activities 2 (R-IDDD2), which
      comprised new activities such as computer use, as well as sub-activities on the
      performance scale. Carers also completed questionnaires assessing patient quality
      of life (QoL-AD), carer quality of life (AC-QoL), and burden (GHQ-12). RESULTS:
      Persons with dementia were significantly poorer initiating than performing
      cleaning, doing repair work, and preparing a hot or cold meal, whereas being
      poorer at performing dressing and following current affairs. Using the computer,
      preparing a hot meal, finance, and medication management were most impaired,
      whereas more basic activities of dressing, washing oneself, brushing hair or
      teeth, and preparing a hot drink were most preserved. Poor initiative and
      performance on nearly all activities were significantly related to reduced carer
      and patient well-being. CONCLUSIONS: The R-IDDD2 offers a platform to
      comprehensively assess everyday functioning. Deteriorations in initiative and
      performance need to be targeted separately in interventions, as the former
      requires effective triggering and the latter structured training and support.
      Most activities were significantly associated with well-being, particularly
      patient quality of life so that improving any activity should improve well-being.

PMID- 27890029
TI  - Keeping the person with dementia and the informal caregiver together: a
      systematic review of psychosocial interventions.
AB  - BACKGROUND: Social support, relationships, and closeness are emphasized as
      important by both people with dementia and their informal caregivers.
      Psychosocial interventions might be helpful to reinforce the relationship between
      a person with dementia and his or her informal caregiver. Therefore, this review
      explores what types of psychosocial interventions have been provided for people
      with dementia and their informal caregivers together, and the effectiveness of
      these interventions. METHODS: PubMed, PsychInfo, Cinahl, and references of key
      papers were searched for studies describing a psychosocial intervention for
      people with dementia and their informal caregivers together. Psychosocial
      interventions were defined as focusing primarily on psychological or social
      factors. RESULTS: A total of seven publications describing six studies were
      identified as eligible for inclusion in this review. Interventions ranged in
      focus from skills training to viewing/making art. The methodology of the studies
      varied, especially regarding the outcome measures used. The results of individual
      studies were mixed. A narrative synthesis of the included studies is given.
      CONCLUSION: Although caregiving dyads emphasize the importance of their
      relationship, this is mostly not taken into consideration in the design and
      effect evaluations of the interventions. Improved research is needed on this
      subject, which focuses on people with dementia living in the community and those
      living in nursing homes.

PMID- 27890030
TI  - Longitudinal Emergency Medical Technician Attributes and Demographic Study
      (LEADS) Design and Methodology.
AB  - OBJECTIVES: The objective of this study is to describe the Longitudinal Emergency
      Medical Technician (EMT) Attributes and Demographic Study (LEADS) design,
      instrument development, pilot testing, sampling procedures, and data collection
      methodology. Response rates are provided, along with results of follow-up surveys
      of non-responders (NRs) and a special survey of Emergency Medical Services (EMS)
      professionals who were not nationally certified. METHODS: Annual surveys from
      1999 to 2008 were mailed out to a random, stratified sample of nationally
      registered EMT-Basics and Paramedics. Survey weights were developed to reflect
      each respondent's probability of selection. A special survey of NRs was mailed
      out to individuals who did not respond to the annual survey to estimate the
      probable extent and direction of response bias. Individuals who indicated they
      were no longer in the profession were mailed a special exit survey to determine
      their reasons for leaving EMS. RESULTS: Given the large number of comparisons
      between NR and regular (annual) survey respondents, it is not surprising that
      some statistically significant differences were found. In general, there were few
      differences. However, NRs tended to report higher annual EMS incomes, were
      younger, healthier, more physically fit, and were more likely to report that they
      were not practicing EMS. Comparisons of the nationally certified EMS
      professionals with EMS professionals who were not nationally certified indicated
      that nationally certified EMS providers were younger, had less EMS experiences,
      earned less, were more likely to be female and work for private EMS services, and
      less likely to work for fire-based services. These differences may reflect state
      and local policy and practice, since many states and local agencies do not
      require maintenance of national certification as a requirement to practice. When
      these differences were controlled for statistically, there were few systematic
      differences between non-nationally certified and nationally certified EMS
      professionals. CONCLUSIONS: The LEADS study is the only national, randomized, and
      longitudinal data source for studying EMS professionals in the United States.
      Although not without flaws, this study remains an excellent source of information
      about EMS provider demographics, attributes, attitudes, workplace issues and
      concerns, and how the profession has changed from 1999 to 2008. Levine R .
      Longitudinal Emergency Medical Technician Attributes and Demographic Study
      (LEADS) design and methodology. Prehosp Disaster Med. 2016;31(Suppl. 1):s7-s17.

PMID- 27890031
TI  - A National Assessment of the Health and Safety of Emergency Medical Services
      Professionals.
AB  - OBJECTIVES: The objectives were to assess changes in (1) health and physical
      fitness, (2) the prevalence of selected health problems, (3) risk behaviors, (4)
      ambulance safety issues, and (5) the preparedness of Emergency Medical Services
      (EMS) professionals. In addition, the incidence of patient-initiated violence
      directed toward EMS personnel and associated factors were assessed. METHODS: Data
      were obtained from a sample of nationally certified EMS professionals via annual
      questionnaires between 1999 and 2008. Stratification was based upon national
      certification level, self-reported race, and experience level. Weighted
      percentages, averages for continuous variables, and 95% confidence intervals
      (CIs) were calculated. Significant changes over time were noted by lack of CI
      overlap. RESULTS: The proportion reporting "excellent" health declined
      significantly from 1999 (38.5%) to 2008 (32.2%). High rates of sleeping problems
      (20%-27%), back problems (20%-24%), and hearing problems (7%-10%) were reported
      as having occurred in the past year. These rates remained constant over time. As
      a result of sleepiness, 8.0% of nationally certified EMS professionals reported
      difficulty in driving an emergency vehicle for short distances and 17.5% reported
      difficulty in driving long distances. The proportion of daily tobacco smokers
      significantly declined from over one-third (35.3%) to about one-fifth (20.3%).
      The proportion of providers who had ever been involved in an ambulance crash
      increased slightly from 2004 (14.5%) to 2008 (15.8%). In 2000, the majority of
      EMS professionals reported that they and/or their partner had been assaulted by a
      patient. Finally, there was a significant decrease in the amount of training time
      devoted to the recognition of biological, chemical, and nuclear (BCN) threats,
      use of personal protective equipment (PPE), and treatment and management of
      patients exposed to BCN from an average from 8.4 hours in 2003 to 6.2 hours in
      2008. CONCLUSIONS: The overall health and physical fitness of EMS professionals
      as well as their health problems, risk behaviors, ambulance safety, and patient
      initiated violence in the prehospital emergency setting are areas of concern for
      the nation's emergency medical system. The prevalence of these problems and
      overall health and physical fitness has shown little or no improvement from 1999
      to 2008. Bentley MA , Levine R . A national assessment of the health and safety
      of Emergency Medical Services professionals. Prehosp Disaster Med. 2016;31(Suppl.
      1):s96-s104.

PMID- 27890032
TI  - Ageism: we are our own worst enemy.
AB  - In 1969, Butler (1969) first coined the term "ageism" to confront "prejudice by
      one age group toward other age groups" (pp. 243). As with other "isms," such as
      racism and sexism, ageism leads to bigotry and discrimination, though it is a
      very distinct beast in that, for the most part, other "isms" refer to those
      different from ourselves: distinct, mutually exclusive, and impervious groups.
      Conversely, age is a fluid social construct in which we are all intimately bound
      as we move through the lifespan, transitioning in and out of different age
      groups. Unlike other "isms," individuals negotiate shifts from the "in-group" of
      youth to the "out-group" of old age. Yet we are all immersed, largely
      unconsciously, in this ubiquitous but too often unrecognized "ism" that needs to
      be named and challenged.

PMID- 27890033
TI  - IL-8/IL-17 gene variations and the susceptibility to severe viral bronchiolitis.
AB  - Clinical manifestations of acute bronchiolitis (AB) vary from minimal disease to
      severe respiratory failure. The response to respiratory viral infections is
      possibly influenced by genetic polymorphisms linked to the regulation of the
      inflammatory response. In the present study, we investigated whether interleukin
      8 (IL-8) and interleukin-17 (IL-17) genetic variants are associated with the
      severity of AB. A group of Brazilian infants hospitalized with AB and a control
      group (infants with no or mild AB, without hospitalization) were genotyped for
      four IL-8/IL-17 variations. For replication, we studied an Argentinean population
      sample of infants with mild and severe AB. IL-8 polymorphism (rs 2227543) and IL
      17 (rs2275913) variants showed significant associations with the severity of AB.
      The effect of the IL-8 variation could be replicated in the Argentinean sample.
      This finding suggests that IL-8 variations may influence the severity of AB in
      young infants. Further genetic association studies in low- or middle-income
      populations are necessary with the aim of expanding knowledge in this area.

PMID- 27890034
TI  - Do Patients Get Whacked When Hospitals Get HACed?

PMID- 27890035
TI  - Epigenetics in type 1 diabetes: TNFa gene promoter methylation status in Chilean
      patients with type 1 diabetes mellitus.
AB  - TNF-alpha is a pro-inflammatory cytokine that is involved in type 1 diabetes
      (T1D) pathogenesis. The TNFa gene is subject of epigenetic regulation in which
      folate and homocysteine are important molecules because they participate in the
      methionine cycle where the most important methyl group donor (S
      adenosylmethionine) is formed. We investigated whether TNFa gene promoter
      methylation status in T1D patients was related to blood folate, homocysteine and
      TNF-alpha in a transversal case-control study. We studied T1D patients (n 25,
      mean=13.7 years) and healthy control subjects (n 25, mean=31.1 years), without
      T1D and/or other autoimmune diseases or direct family history of these diseases.
      A blood sample was obtained for determination of serum folate, plasma
      homocysteine and TNF-alpha concentrations. Whole blood was used for the
      extraction of DNA to determine the percentage of methylation by real-time PCR and
      melting-curve analysis. Results are expressed as means and standard deviations
      for parametric variables and as median (interquartile range) for non-parametric
      variables. T1D patients showed a higher TNFa gene promoter methylation (39.2 (sd
      19.5) %) when compared with control subjects (25.4 (sd 13.7) %) (P=0.008). TNFa
      gene promoter methylation was positively associated only with homocysteine levels
      in T1D patients (r 0.55, P=0.007), but not in control subjects (r -0.122,
      P=0.872). To our knowledge, this is the first work that reports the methylation
      status of the TNFa gene promoter and its relationship with homocysteine
      metabolism in Chilean T1D patients without disease complications.

PMID- 27890036
TI  - Treatment preferences for depression in the elderly.
AB  - BACKGROUND: If patients are treated according to their personal preferences,
      depression treatment success is higher. It is not known which treatment options
      for late-life depression are preferred by patients aged 75 years and over and
      whether there are determinants of these preferences. METHODS: The data were
      derived from the German "Late-life depression in primary care: needs, health care
      utilization, and costs (AgeMooDe)" study. Patients aged 75+ years (N = 1,230)
      were recruited from primary care practices. Depressive symptoms were determined
      using the Geriatric Depression Scale (GDS-15). Support for eight treatment
      options was determined. RESULTS: Medication, psychotherapy, talking to friends
      and family, and exercise were the preferred treatment options. Having a GDS score
      >= 6 significantly lowered the endorsement of some treatment options. For each
      treatment option, the probability of choosing the indecisive category "I do not
      know" was significantly increased in participants with moderate depressive
      symptoms. CONCLUSIONS: Depressive symptoms influence the preference for certain
      treatment options and also increase indecision in patients. The high preference
      for psychotherapy suggests a much higher demand for late-life psychotherapy in
      the future. Healthcare systems should begin to prepare to meet this anticipated
      need. Future studies should include previous experience with treatment methods as
      a confounding variable.

PMID- 27890037
TI  - Grouped Cases of Pulmonary Pneumocystosis After Solid Organ Transplantation:
      Advantages of Coordination by an Infectious Diseases Unit for Overall Management
      and Epidemiological Monitoring.
AB  - OBJECTIVE To determine the origin of grouped cases of Pneumocystis pneumonia in
      solid-organ transplant recipients at our institution. DESIGN A case series with
      clinical examinations, genotyping, and an epidemiological survey. SETTING A
      university hospital in France. PATIENTS We report 12 solid-organ transplant
      recipients with successive cases of Pneumocystis pneumonia that occurred over 3
      years; 10 of these cases occurred in a single year. METHODS We used molecular
      typing of P. jirovecii strains by multilocus sequence typing and clinical
      epidemiological survey to determine potential dates and places of transmission.
      RESULTS Between May 2014 and March 2015, 10 solid-organ transplant recipients (5
      kidney transplants, 4 heart transplants, and 1 lung transplant) presented with
      Pneumocystis pneumonia. Molecular genotyping revealed the same P. jirovecii
      strain in at least 6 patients. This Pneumocystis strain was not identified in
      control patients (ie, nontransplant patients presenting with pulmonary
      pneumocystosis) during this period. The epidemiological survey guided by
      sequencing results provided information on the probable or possible dates and
      places of contamination for 5 of these patients. The mobile infectious diseases
      unit played a coordination role in the clinical management (adaptation of the
      local guidelines) and epidemiological survey. CONCLUSION Our cardiac and kidney
      transplant units experienced grouped cases of pulmonary pneumocystosis.
      Genotyping and epidemiological surveying results suggested interhuman
      contamination, which was quickly eliminated thanks to multidisciplinary
      coordination. Infect Control Hosp Epidemiol 2017;38:179-185.

PMID- 27890038
TI  - An Evaluation of Antibiotic Prescribing Practices Upon Hospital Discharge.
AB  - We conducted a retrospective study of the appropriateness of antimicrobial agents
      prescribed on discharge from an acute care hospital. Seventy percent of discharge
      antibiotics were inappropriate in antibiotic drug choice, dose, or duration. Our
      findings suggest there is a significant need for antimicrobial stewardship at
      transitions in care. Infect Control Hosp Epidemiol 2017;38:353-355.

PMID- 27890039
TI  - Genetic diversity of infective larvae of Gnathostoma spinigerum (Nematoda:
      Gnathostomatidae) in freshwater swamp eels from Thailand.
AB  - Human gnathostomiasis is a food-borne zoonosis caused by a tissue nematode of the
      genus Gnathostoma. The disease is highly endemic in Asia, including Thailand. The
      freshwater swamp eel (Monopterus albus), the second intermediate host of the
      gnathostome nematode, has an important role in transmitting the infection in
      Thailand. Surveys on the infective larvae of Gnathostoma spinigerum based on
      morphological features in freshwater swamp eels have been performed continuously
      and reported in Thailand. However, there is still limited molecular data on intra
      species variations of the parasite. In this study, a total of 19 third-stage
      larvae of morphologically identified G. spinigerum were collected from 437 liver
      samples of freshwater swamp eels purchased from a large wholesale market in
      Bangkok, Thailand. Molecular characterization based on mitochondrial cytochrome c
      oxidase subunit I (COI) sequences was performed to elucidate their genetic
      variations and phylogenetic relationship. Among the 19 infective larvae recovered
      from these eels, 16 were sequenced successfully. Phylogenetic analyses inferred
      from the partial COI gene showed the presence of three distinct COI haplotypes.
      Our findings confirm the presence of G. spinigerum as the main species in
      Thailand.

PMID- 27890040
TI  - High prevalence of Legionella in non-passenger merchant vessels.
AB  - There is a paucity of information on the risk from potable water in non-passenger
      merchant vessels (NPMVs) particularly with regard to Legionella and other
      bacteria. This retrospective study examined water samples from 550 NPMVs docked
      in eight UK ports. A total of 1027 samples from 412 NPMVs were examined for total
      aerobic colony counts (ACC), coliforms, Escherichia coli and enterococci; 41% of
      samples yielded ACC above the action level (>1 * 103 c.f.u./ml) and 4.5%
      contained actionable levels (>1 c.f.u./100 ml) of faecal indicator bacteria.
      Eight hundred and three samples from 360 NPMVs were cultured specifically for
      Legionella and 58% of vessels proved positive for these organisms with 27% of
      samples showing levels greater than the UK upper action limit of 1 * 103
      c.f.u./l. Cabin showers (49%) and hospital shower (45%) were frequently positive.
      A subset of 106 samples was analysed by quantitative polymerase chain reaction
      for Legionella and identified a further 11 Legionella-positive NPMVs, returning a
      negative predictive value of 100%. There was no correlation between NPMV age or
      size and any microbial parameters (P > 0.05). Legionella pneumophila serogroup 1
      was isolated from 46% of NPMVs and sequence-based typing of 17 isolates revealed
      four sequence types (STs) previously associated with human disease. These data
      raise significant concerns regarding the management of microbial and Legionella
      risks on board NPMVs and suggest that better guidance and compliance are required
      to improve control.

PMID- 27890041
TI  - Introduction: plurality in patenting: medical technology and cultures of
      protection.

PMID- 27890042
TI  - USE OF MALE METHODS OF CONTRACEPTION WORLDWIDE.
AB  - This article analyses male contraceptive use, both globally and for developing
      countries. Shares of all contraceptive use due to males are examined, in the
      context of female use and all use. Patterns according to wealth quintiles are
      analysed, as well as time trends and geographic variations. Data are drawn
      primarily from compilations by the UN Population Division and from the
      Demographic and Health Series and subjected to relatively simple statistical
      methods including correlation/regression applications. Contraceptive methods that
      men use directly, or that require their co-operation to use, including condoms,
      withdrawal, rhythm and male sterilization, account for one-quarter of all
      contraceptive use worldwide. This represents 13% of married/in-union women. Both
      the share and the prevalence of male methods vary widely by geography and by the
      four methods, as well as by quintile wealth groups. With greater wealth there is
      an unbroken rise for total use; among the male methods, the shares of condom use
      and rhythm rise by wealth quintiles, while the share of withdrawal drops. The
      share for male sterilization is highest in the lowest and highest wealth
      quintiles and dips for the middle quintiles. The overall time trend since the
      1980s has been steady at one-quarter of all use involving men; moreover, the
      share is about the same at all levels of total use. The female-only methods
      continue to dominate: female sterilization, IUD, pill, injectable and implant,
      again with great diversity geographically. In surveys men report less total use
      but more condom use, while females report more injectable use. For the future the
      male share of one-quarter of use seems secure, with little prospect of an
      increase unless concerted programmatic efforts are made to expand access to male
      methods and promote their use as part of a broadened contraceptive method mix.

PMID- 27890043
TI  - Epidemic host community contribution to mosquito-borne disease transmission: Ross
      River virus.
AB  - Most vector-borne diseases infect multiple host species, but disentangling the
      relative importance of different host species to transmission can be complex.
      Here we study how host species' abundance and competence (duration and titre of
      parasitaemia) influence host importance during epidemic scenarios. We evaluate
      this theory using Ross River virus (RRV, family Togaviridae, genus Alphavirus), a
      multi-host mosquito-borne disease with significant human health impacts across
      Australia and Papua New Guinea. We used host contribution models to find the
      importance of key hosts (possums, wallabies, kangaroos, horses, humans) in
      typical mammal communities around five Australian epidemic centres. We found
      humans and possums contributed most to epidemic RRV transmission, owing to their
      high abundances, generally followed by macropods. This supports humans as
      spillover hosts, and that human-mosquito and possum-mosquito transmission is
      predominant during epidemics. Sensitivity analyses indicate these findings to be
      robust across epidemic centres. We emphasize the importance of considering
      abundance and competence in identifying key hosts (during epidemics in this
      case), and that competence alone is inadequate. Knowledge of host importance in
      disease transmission may help to equip health agencies to bring about greater
      effectiveness of disease mitigation strategies.

PMID- 27890044
TI  - Effect of dietary manganese on antioxidant status and expressions of heat shock
      proteins and factors in tissues of laying broiler breeders under normal and high
      environmental temperatures.
AB  - To investigate the effect of Mn on antioxidant status and on the expressions of
      heat shock proteins/factors in tissues of laying broiler breeders subjected to
      heat challenge, we used a completely randomised design (n 6) with a factorial
      arrangement of 2 environmental temperatures (normal, 21+/-1 degrees C, and high,
      32+/-1 degrees C)*3 dietary Mn treatments (a Mn-unsupplemented basal diet (CON),
      or a basal diet supplemented with 120 mg Mn/kg diet, either as inorganic Mn
      sulphate (iMn) or as organic Mn proteinate (oMn)). There were no interactions
      (P>0.10) between environmental temperature and dietary Mn in any of the measured
      indices. High temperature decreased (P<0.003) Mn content, and also tended
      (P=0.07) to decrease Cu Zn superoxide dismutase (CuZnSOD) activity in the liver
      and heart. However, an increased Mn superoxide dismutase (MnSOD) activity
      (P<0.05) and a slight increase in malondialdehyde level (P=0.06) were detected in
      breast muscle. Up-regulated (P<0.05) expressions of heat shock factor 1 (HSF1)
      and HSF3 mRNA and heat shock protein 70 (HSP70) mRNA and protein were found in
      all three tissues. Broiler breeders fed either iMn or oMn had higher tissue Mn
      content (P<0.0001), heart MnSOD and CuZnSOD activities (P<0.01) and breast muscle
      MnSOD protein levels (P<0.05), and lower (P<0.05) breast muscle HSP70 mRNA and
      protein levels compared with those fed CON. Broiler breeders fed oMn had higher
      (P<0.03) bone Mn content than those fed iMn. These results indicate that high
      temperature decreases Mn retention and increases HSP70, HSF1 and HSF3 expressions
      in the tissues of laying broiler breeders. Furthermore, dietary supplementation
      with Mn in either source may enhance the heart's antioxidant ability and inhibit
      the expression of HSP70 in breast muscle. Finally, the organic Mn appears to be
      more available than inorganic Mn for bone in laying broiler breeders regardless
      of environmental temperatures.

PMID- 27890045
TI  - Protein in culture and endogenous lipid interact with embryonic stages in vitro
      to alter calf birthweight after embryo vitrification and warming.
AB  - Short-term protein removal in vitro improves long-term blastocyst competence to
      survive vitrification. We investigated the mechanisms and effects underlying
      protein removal. Day-6 morulae and early blastocysts were cultured individually
      with and without protein for 24h. Development and lipid content were analysed in
      expanded blastocysts derived from morulae (M-XB) and from early blastocysts (EB
      XB). Expression of genes involved in lipid metabolism, stress responses and
      apoptosis was analysed in fresh and vitrified-warmed M-XB produced with and
      without protein. Pregnancy rates, birth rates and birthweight (BW) were recorded
      after transfer of embryos. Day-7 EB-XB production rates (with, 66.9+/-6.2 and
      without, 68.8+/-6.0 protein) were higher than M-XB rates (with, 21.4+/-4.6 and
      without, 9.4+/-4.6 protein; P<0.005). EB-XB showed fewer lipids than M-XB
      (P=0.03). In fresh M-XB, expression of sterol regulatory element binding protein
      (SREBP1) was lower with (4.1+/-2.2) than without (13.6+/-2.2) protein, contrary
      to results obtained for Patatin-like phospholipase domain containing 2, Hormone
      sensitive lipase and Bcl-2-associated X protein (P<0.05). Protein did not affect
      pregnancy rates and birth phenotypes (P>0.05). However, BW was higher (P<0.01) in
      calves born from vitrified M-XB (48.6+/-3.4kg) than from EB-XB (39.8+/-2.9kg).
      Such effects were more pronounced in females (P<0.001). Calves from fresh embryos
      did not show BW differences. These results indicate that embryonic kinetics and
      vitrification impact birth phenotypes, at least in females. Alterations might
      involve exogenous protein and mobilisation of lipid stocks.

PMID- 27890046
TI  - Investigation of training and support needs in rural and remote disability and
      mainstream service providers: implications for an online training model.
AB  - Objectives It is known that there are difficulties in recruiting and retaining
      practitioners in rural and remote communities and that access to support and
      professional development can be key in breaking this cycle. Technology provides a
      possible solution not only for increasing access to these opportunities, but also
      in building community capacity to support children with autism. The aim of the
      present study was to investigate the current learning and support needs within
      rural and remote professionals prior to setting up a model of support. Methods An
      online survey was used to gather information from service providers in rural and
      remote communities on their demographics, current skills and confidence in
      working with clients on the autism spectrum, current supervision and professional
      development, identified learning and support needs, and the availability and
      uptake of technology for accessing professional development. Results Respondents
      reported below average levels of perceived confidence and skills when working
      with children with autism, most notably children with challenging behaviour. Half
      the respondents do not currently attend supervision sessions, with only 15%
      receiving regular supervision (fortnightly or more often), and 66% of respondents
      had travelled more than 3h to access professional development workshops. The
      majority of participants had access to technology and over half had already used
      this for online training. Conclusion Overall, service providers in rural and
      remote areas are generally not currently meeting their needs in terms of
      frequency of supervision and professional development. The present needs analysis
      identifies key areas for learning, the ideal frequency of support and the
      acceptability of using technology to deliver this support. This information will
      guide future researchers in the development of an evidence-based model that will
      be accessible and meaningful to its participants. What is known about the topic?
      It is known that there are difficulties in recruiting and retaining practitioners
      in rural and remote communities and that access to support and professional
      development can be key in breaking this cycle, which may be triggered by
      geographical isolation. Technology-delivered intervention and support, also known
      as eHealth or Telehealth, has been used successfully in the disability sector for
      medical rehabilitation, direct intervention, employment support and support
      groups, but there is little evidence as to how technology is received by and
      implemented with disability and mainstream service providers supporting children
      with autism living in remote regions. What does this paper add? This paper
      provides an insight into the current skills and confidence of a broad range of
      service providers, including educators, allied health therapists and therapy and
      community support workers, in working with children with autism. This paper also
      investigates the experience, feasibility and potential uptake of a technology
      driven program of support and professional development in rural and remote
      Australia. Finally, this paper provides an insight into the desired frequency of
      training and support, as well as identified learning support needs. What are the
      implications for practitioners? These findings have and will continue to guide
      practitioners in the development of an evidence-based, technology-driven model of
      supporting rural and remote staff working with children with autism. Technology
      has the potential to provide practitioners in geographically isolated areas with
      access to more responsive, collaborative and individualised professional support
      and training. Such practice may improve the skills of practitioners and the level
      of support they can provide their clients with autism, with the added potential
      of increasing staff retention in rural and remote areas of Australia.

PMID- 27890047
TI  - A clear urban-rural gradient of allergic rhinitis in a population-based study in
      Northern Europe.
AB  - BACKGROUND: The protective effect of farm upbringing on allergic rhinitis is well
      known, but how upbringing in other environments influences the development of
      allergic rhinitis is scarcely investigated. The aim of this study was to
      investigate the association between place of upbringing and pet keeping in
      childhood and allergic rhinitis and nasal symptoms in adulthood. METHODS: The
      population-based Respiratory Health in Northern Europe study includes subjects
      from Denmark, Norway, Sweden, Iceland, and Estonia born in 1945-1973. This paper
      analyses 13,376 participants of the third study wave. Six categories of place of
      upbringing were defined: farm with livestock, farm without livestock, village in
      rural area, small town, city suburb, and inner city. Pets in the home at birth
      and during childhood were recorded. Data were analysed using adjusted logistic
      regression models. RESULTS: Livestock farm upbringing predicted less adult
      allergic rhinitis [odds ratio (OR) 0.68, 0.54-0.85] and nasal symptoms (OR 0.82,
      0.68-0.99) than city upbringing, and an urban-rural gradient with decreasing risk
      per level of urbanisation was observed (OR 0.92, 0.88-0.94). Pets in the home at
      birth (OR 0.78, 0.68-0.88) and during childhood (OR 0.83, 0.74-0.93) were
      associated with less subsequent allergic rhinitis. Pet keeping did not explain
      the protective effect of place of upbringing. CONCLUSION: Risk of allergic
      rhinitis and nasal symptoms in adulthood was inversely associated with the level
      of urbanisation during upbringing. Pets at birth decreased the risk further, but
      did not explain the urban-rural gradient. Persistent beneficial effects of
      microbial diversity in early life might be an explanation for the findings.

PMID- 27890048
TI  - Cultural hegemony? Educators' perspectives on facilitating cross-cultural
      dialogue.
AB  - BACKGROUND: We live in an age when education is being internationalized. This can
      confront students with 'cultural hegemony' that can result from the unequal
      distribution of power and privilege in global society. The name that is given to
      awareness of social inequality is 'critical consciousness'. Cross-cultural
      dialogue provides an opportunity for learners to develop critical consciousness
      to counter cultural hegemony. The purpose of this research was to understand how
      learners engage with cross-cultural dialogue, so we can help them do so more
      effectively in the future. METHOD: The setting for this research was an online
      discussion in an international health professions educator fellowship program. We
      introduced scenarios with cultural references to study the reaction of
      participants to cultural conversation cues. We used an inductive thematic
      analysis to explore power and hegemony issues. RESULTS: Participants reflected
      that personally they were more likely to take part in cross-cultural discussions
      if they recognized the context discussed or had prior exposure to educational
      settings with cultural diversity. They identified barriers as lack of skills in
      facilitating cross-cultural discussions and fear of offending others. They
      suggested deliberately introducing cultural issues throughout the curriculum.
      CONCLUSION: Our results indicate that developing critical consciousness and cross
      cultural competency will require instructional design to identify longitudinal
      opportunities to bring up cross-cultural issues, and training facilitators to
      foster cross-cultural discussions by asking clarifying questions and navigating
      crucial/sensitive conversations.

PMID- 27890049
TI  - Medication Safety-Models of Interprofessional Collaboration.

PMID- 27890050
TI  - Interprofessional Medication Management in Patients With Multiple Morbidities.
AB  - BACKGROUND: Medication reviews and medication management are being used more and
      more around the world to improve medication safety. Both of these tools were
      originally conceived as pharmaceutical care activities and have recently been
      developed into interdisciplinary approaches. We studied the efficacy of
      interprofessional medication management for multimorbid patients that takes their
      medical conditions, but also their general living situation into account.
      METHODS: A comprehensive medication management was performed, which involved the
      collection of information on the drugs each patient took, the way they were
      stored, the patient's drug intake and handling, and any problems that arose with
      pharmacotherapy. The interventional approach was evaluated over a period of 15
      months in a cluster-randomized controlled trial with a stepped wedge design. The
      primary endpoint was the quality of pharmacotherapy, as assessed with the
      Medication Appropriateness Index (MAI). A mixed model was used to analyze
      efficacy. RESULTS: 162 patients were enrolled in the study; 142 were included in
      the intention-to-treat analysis (53.3% women, mean age 76.8 +/- 6.3 years). The
      mean total MAI score decreased significantly (p <= 0.001) from the control phase
      (29.21, 95% CI [26.09; 32.33]) to the intervention phase (22.27 [19.00; 25.54]),
      with an effect strength (Cohen's d) of -0.24 [-0.36; -0.13]. The number of drug
      related problems declined as well. CONCLUSION: In this study, interprofessional
      collaboration increased medication safety. Working across disciplinary boundaries
      allowed for a decrease in drugrelated problems and brought up aspects outside the
      purview of the primary care physician.

PMID- 27890051
TI  - Medication and Treatment Adherence Following Hospital Discharge.
AB  - BACKGROUND: Patients' drug regimens often need to be changed when they pass from
      one care sector to another, but these changes sometimes pose a safety risk. To
      avoid such risks, a new inter-sector transition concept was developed
      incorporating discharge medication plans and counseling modules for the patients
      themselves and the doctors receiving them into their care. METHODS: A prospective
      interventional trial was carried out in two internal medicine wards of a general
      hospital. After data acquisition from the control group, the transition concept
      was developed and evaluated in an independent intervention group. The discharge
      medication plan and the first post-discharge prescription were compared to
      identify patients who had at least one medication change that increased the post
      discharge risk of either failure to achieve the therapeutic goal (category A,
      first endpoint) or of patient's lack of treatment adherence (category B). Gaps in
      care after discharge were also analyzed. RESULTS: 200 consecutive patients were
      enrolled in the trial. In the intention-to-treat analysis, the percentage of
      patients with potentially jeopardizing medication changes in category A declined
      from 54% (54/100) in the control group to 15% (15/100) in the intervention group.
      (p<0.001). For medication changes in category B, there was a corresponding
      decline from 53% (53/100) to 7% (7/100) (p < 0.001). Gaps in care were seen in
      28% (28/100) of control patients and 18% (18/100) of patients in the intervention
      group (p = 0.031). CONCLUSION: The likelihood of a potentially jeopardizing
      medication change upon hospital discharge can be markedly reduced with the aid of
      a modular transition concept. Gaps in care can be closed in this way as well.

PMID- 27890052
TI  - The Power of Generosity.

PMID- 27890053
TI  - The Value of a Nurse Scientist in the Perioperative Setting.

PMID- 27890054
TI  - Results of the 2016 AORN Salary and Compensation Survey.
AB  - AORN conducted its 14th annual compensation survey for perioperative nurses in
      June 2016. A multiple regression model was used to examine how several variables,
      including job title, education level, certification, experience, and geographic
      region, affect nurse compensation. Comparisons between the 2016 data and data
      from previous years are presented. The effects of other forms of compensation
      (eg, on-call compensation, overtime, bonuses, shift differentials, benefits) on
      base compensation rates also are examined. Additional analyses explore the effect
      of the economic downturn on the perioperative work environment.

PMID- 27890055
TI  - Overview of Recent Issues and Advances in Infection Prevention.

PMID- 27890056
TI  - Patient Care Interventions to Reduce the Risk of Surgical Site Infections.

PMID- 27890057
TI  - Optimal Infection Control Practices in the OR Environment.

PMID- 27890058
TI  - Disinfection and Sterilization: Emerging Trends and Technologies.

PMID- 27890059
TI  - Looking Forward-Infection Prevention in 2017.

PMID- 27890060
TI  - Implementing No Interruption Zones in the Perioperative Environment.
AB  - The perioperative arena is one of the most information-intensive, intricate, and
      complex work environments in health care, and it depends on sound communication
      to help ensure patient safety. Surgical procedures require attention, vigilance,
      and situational awareness. Noise and other distractions have the potential to
      cause mental lapses, impair thought processes, and divert attention away from
      tasks, increasing the likelihood of adverse patient events. However, there is no
      way to eliminate all noise from an OR. AORN advocates for a controlled
      environment in which distractions and noise are minimized. Our project presents
      an overview of how the No Interruption Zone concept was introduced in an
      outpatient surgical setting through an educational intervention. Our findings
      suggest that noise levels during critical phases of surgery can be reduced
      through focused education for perioperative team members.

PMID- 27890061
TI  - Preoperative Screening for Sleep-Disordered Breathing in Children: A Systematic
      Literature Review.
AB  - Clinicians frequently underestimate or do not assess sleep-disordered breathing
      (SDB) in children in ambulatory surgical centers. Identifying the disorder and
      obtaining information relevant to anesthesia management can be assisted by the
      use of a standard questionnaire during preoperative assessment. We wanted to
      determine whether a preoperative screening tool increases clinician awareness of
      SDB in children and leads to a decrease in perioperative respiratory adverse
      events. We reviewed 21 articles to identify reliable screening tools for
      pediatric SDB in ambulatory surgical centers and selected six articles for the
      review. We concluded that the Snoring, Trouble Breathing, Un-Refreshed
      questionnaire is a reliable preoperative SDB identification tool and that
      awareness of preexisting SDB in children presenting for surgery in ambulatory
      surgical centers aids in designing a patient-specific plan of care to reduce
      perioperative respiratory adverse events. Standardizing the use of the Snoring,
      Trouble Breathing, Un-Refreshed questionnaire during the preoperative evaluation
      is a safety measure for pediatric surgical patients.

PMID- 27890062
TI  - A Nurse-Initiated Perioperative Pressure Injury Risk Assessment and Prevention
      Protocol.
AB  - Pressure injuries negatively affect patients physically, emotionally, and
      economically. Studies report that pressure injuries occur in 69% of inpatients
      who have undergone a surgical procedure while hospitalized. In 2012, we created a
      nurse-initiated, perioperative pressure injury risk assessment measure for our
      midwestern, urban, adult teaching hospital. We retrospectively applied the risk
      assessment to a random sample of 350 surgical patients which validated the
      measure. The prospective use of the risk assessment and prevention measures in
      350 surgical patients resulted in a 60% reduction in pressure injuries compared
      with the retrospective group. Our findings support the use of a multipronged
      approach for the prevention of health care-associated pressure injuries in the
      surgical population, which includes assessment of risk, implementation of
      evidence-based prevention interventions for at-risk patients, and continuation of
      prevention beyond the perioperative setting to the nursing care unit.

PMID- 27890063
TI  - Guideline Implementation: Patient Information Management.
AB  - Clinical documentation captured in a patient's record provides health care
      personnel with information that can be used to guide patient care. Data collected
      in electronic health records can be accessed and aggregated across the health
      care delivery system to enhance the safety, quality, and efficacy of care. The
      updated AORN "Guideline for patient information management" provides guidance to
      perioperative personnel on documenting and managing patient information. This
      article focuses on key points of the guideline, which address data capture that
      supports the clinical workflow, incorporation of professional guidelines and
      standards as well as regulatory and mandatory reporting elements, use of
      standardized clinical terminologies, data aggregation for use in research and
      analytics, considerations for patient care orders, and safeguards for the
      patient's security and confidentiality. Perioperative RNs should review the
      complete guideline for additional information and for guidance when writing and
      updating policies and procedures.

PMID- 27890064
TI  - Guideline Summary: Patient Information Management.

PMID- 27890065
TI  - Advancing Perioperative Nursing in Rwanda Through Global Partnerships and
      Collaboration.

PMID- 27890066
TI  - Instrument Count Sheets and Set Reviews as Patient Safety Tools.

PMID- 27890067
TI  - Clinical Issues-December 2016.
AB  - Head coverings Key words: head cover, bouffant, skull cap, hair, scalp. Skin
      preps Key words: skin preps, antiseptics, cesarean delivery, surgical site
      infections, abdomen. Pediatric surgical counts Key words: pediatrics, counts,
      surgical, retained surgical items, policy. Sterile set up Key words: sterile
      table, sterile set up, covering, monitoring, contamination. Surgical hand
      antisepsis Key words: surgical hand rub, application, surgical scrub, scrubbed
      areas.

PMID- 27890068
TI  - Evidence appraisal of Malik HH, Darwood ARJ, Shaunak S, Kulatilake P, El-Hilly
      AA, Mulki O, Baskaradas A. Three-dimensional printing in surgery: a review of
      current surgical applications.: J Surg Res. 2015;199(2):512-522.

PMID- 27890069
TI  - Guideline at a Glance: Processing Flexible Endoscopes.

PMID- 27890070
TI  - No BP During NIBP.

PMID- 27890071
TI  - Updates on blood transfusion guidelines.

PMID- 27890072
TI  - Nilotinib against high dose imatinib for salvage therapy of chronic myeloid
      leukaemia.

PMID- 27890074
TI  - Foreword.

PMID- 27890073
TI  - Switching to nilotinib versus imatinib dose escalation in patients with chronic
      myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR):
      a randomised, open-label trial.
AB  - BACKGROUND: Optimal management of patients with chronic myeloid leukaemia in
      chronic phase with suboptimal cytogenetic response remains undetermined. This
      study aimed to investigate the safety and efficacy of switching to nilotinib vs
      imatinib dose escalation for patients with suboptimal cytogenetic response on
      imatinib. METHODS: We did a phase 3, open-label, randomised trial in patients
      with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic
      response to imatinib according to the 2009 European LeukemiaNet criteria, in
      Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries).
      Eligible patients were aged 18 years or older with Philadelphia chromosome
      positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative
      Oncology Group performance status of 0-2. Before enrolment, all patients had
      received 3-18 months of imatinib 400 mg once daily and had a suboptimal
      cytogenetic response according to 2009 ELN recommendations, established through
      bone marrow cytogenetics. By use of an interactive response technology using
      fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg
      twice per day or an escalation of imatinib dose to 600 mg once per day (block
      size of 4). Investigators and participants were not blinded to study treatment.
      Crossover was allowed for loss of response or intolerance at any time, or for
      patients with no complete cytogenetic response at 6 months. The primary endpoint
      was complete cytogenetic response at 6 months in the intention-to-treat
      population. Efficacy endpoints were based on the intention-to-treat population,
      with all patients assessed according to the treatment group to which they were
      randomised (regardless of crossover); the effect of crossover was assessed in
      post-hoc analyses, in which responses achieved after crossover were excluded. We
      present the final results at 24 months' follow-up. This study is registered with
      ClinicalTrials.gov (NCT00802841). FINDINGS: Between July 7, 2009, and Aug 29,
      2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib
      and 95 patients were randomly assigned to imatinib. Complete cytogenetic response
      at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 95.18%
      CI 40-61) and 40 of 95 in the imatinib group (42%, 32-53%; difference 7.9% in
      favour of nilotinib; 95% CI -6.2 to 22.0, p=0.31). Excluding responses achieved
      after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of
      95 patients in the imatinib group achieved complete cytogenic response at 6
      months (nominal p=0.058). Grade 3-4 non-haematological adverse events occurring
      in more than one patient were headache (nilotinib group, n=2 [2%, including 1
      after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis
      (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation
      (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to
      nilotinib]). Serious adverse events on assigned treatment were reported in 11
      (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the
      imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five
      (5%) of 93 patients died in the imatinib group; no deaths were treatment-related.
      INTERPRETATION: While longer-term analyses are needed to establish whether the
      clinical benefits observed with switching to nilotinib are associated with
      improved long-term survival outcomes, our results suggest that patients with
      suboptimal cytogenetic response are more likely to achieve improved cytogenetic
      and molecular responses with switching to nilotinib than with imatinib dose
      escalation, although the difference was not statistically significant when
      responses achieved after crossover were included. FUNDING: Novartis
      Pharmaceuticals.

PMID- 27890075
TI  - Clone-specific MYD88 L265P and CXCR4 mutation status can provide clinical utility
      in suspected Waldenstrom macroglobulinemia/lymphoplasmacytic lymphoma.
AB  - MYD88 L265P, a diagnostic marker for lymphoplasmacytic lymphoma (LPL)/Waldenstrom
      macroglobulinemia (WM) can also be detected in other hematopoietic malignancies.
      We demonstrate a novel approach to increase the specificity of this marker for
      WM/LPL diagnosis by combining flow cytometric cell sorting with molecular
      analysis. Clonal B-lymphocyte and co-occurring clonal plasma cell populations of
      low-grade B-cell lymphomas were sorted by flow cytometry and analyzed for
      immunoglobulin gene rearrangements (PCR), and for MYD88 and CXCR4 mutations.
      Identical clonal origin was confirmed by PCR for 21 LPL/WM cases and MYD88 L265P
      was detected in both B-cell and plasma cell fractions. 9/20 other B-cell
      lymphomas with identical light chain restriction on B-cells and plasma cells were
      genotypically identical by PCR and MYD88 L265P was detected in both cell
      fractions in 7/9 whereas in 11/20 specimens with different clonal origin, MYD88
      L265P was absent (5/11), or only found in B-lymphocytes (4/11), or plasma cells
      (2/11). CXCR4 mutations were detected in 17/39 cases, but missed in 63% of these
      without cell sorting. Confirming MYD88L265P in both B-cells and plasma cell
      fractions can provide a novel and powerful discriminator to distinguish LPL/WM
      from phenotypically similar disorders. Furthermore, this approach significantly
      increases CXCR4 detection sensitivity.

PMID- 27890076
TI  - Dirofilaria immitis exhibits sex- and stage-specific differences in
      excretory/secretory miRNA and protein profiles.
AB  - The canine heartworm Dirofilaria immitis releases excretory/secretory molecules
      into its host and in culture. We report analyses of the types, amounts and stage
      dependence of microRNAs and proteins found in D. immitis culture media recovered
      after incubating 800,000 microfilariae for 6days, 500L3 and 500L4 for 7days, as
      well as 40 adult females and 40 adult males for 48h, all separately. In addition,
      the presence of exosome-like particles was established by nanoparticle tracking
      analysis. Our results are in concordance with the D. immitis molecules previously
      detected in dog blood and in culture medium, but add additional insight into the
      sex- and stage-specificity of these processes. Of 131 miRNA candidates analyzed,
      none of the most abundant sequences was exclusively associated with one stage.
      Several isoforms of the nematode miR-100 family, miR-279, miR-71, were highly
      represented and overlapped substantially with the profile of heartworm miRNAs
      described from infected dog blood. lin-4 was primarily associated with males. We
      also report 4, 27 and 72 proteins in media from microfilariae, females and males,
      respectively. The only protein in common to all samples was actin, and only 9/88
      proteins with a gene ontology description had not been reported in other studies
      of filarial secretomes. Exosomal proteins were well represented, dominated by
      cytoskeletal proteins, metabolic enzymes, zeta polypeptide, and chaperones.

PMID- 27890077
TI  - T lymphocyte immunophenotypes in the cerebrospinal fluid of dogs with visceral
      leishmaniasis.
AB  - Visceral leishmaniasis (VL) is a disease causing several clinical manifestations
      in dogs, including neurological disorders. Nevertheless, there are few studies
      related to the evaluation of the brain alterations during VL. Evidences of the
      involvement of cerebral barriers in infected dogs was reported, including the
      presence of brain inflammatory infiltrate, with a predominance of CD3+ T cells.
      Therefore, the aim of this study was to determine the immunophenotypes of T
      lymphocytes in the cerebrospinal fluid (CSF), as well as in peripheral blood, and
      to correlate with brain alterations in dogs with VL. We detected elevated
      percentages of double negative (DN) and double positive (DP) T cells in the CSF,
      with a predominance of TCRalphab. In the histopathological analysis, we observed
      a predominance of lymphoplasmacytic infiltrate, mainly in leptomeninges, ranging
      from mild to intense, and we observed a positive correlation between the
      intensity of inflammation in the subependymal area and the DN T cells of the CSF.
      Thus, the DN T cells seem be acting as villains of the immune system through pro
      inflammatory mechanisms. Further, the proportion of the different population of
      CSF T cells did not differ from those observed in the blood, which provides us
      with more evidence of blood-CSF barrier breakdown. Together, the results provide
      more explanation to the inflammation observed in the brain of dogs with VL, which
      the DN T cells contribute to the origin and progression of the neurological
      disease. This study provides insight into the immunophenotypes of T lymphocytes
      in the CSF during canine visceral leishmaniasis.

PMID- 27890078
TI  - Animal Fascioliasis: Perspectives from high altitudinal regions.
AB  - The parasitic flukes of the genus Fasciola (Platyhelminthes: Trematoda: Digenea)
      cause fascioliasis or liver-rot disease in ruminant livestock in tropical and sub
      tropical regions of the world. Classically, two species of Fasciola- F. hepatica
      and F. gigantica, are universally recognized as taxonomically valid species. Our
      survey studies on ovid and bovid animals including yak and mithun from high
      altitudinal mountainous regions in Northeast India revealed the occurrence of
      Fasciola gigantica and also Fasciola sp.- an intermediate form, at altitudes
      between 5000 and 14,085 feet above sea level (asl). Two morphotypes- F. hepatica 
      like and F. gigantica - like, of Fasciola species were reported from the high
      altitudinal areas of Northeast India; most of these locales constitute new
      locality and first records for the occurrence of these liver flukes.

PMID- 27890079
TI  - Detection of Theileria parva in tissues of cattle undergoing severe East Coast
      fever disease show significant parasite DNA accumulation in the spleen.
AB  - Infiltration and proliferation of Theileria parva infected lymphocytes in bovine
      host lymphoid organs is one of the hallmarks of T. parva infection. The relative
      abundance of parasites within infected host tissues, both lymphoid and non
      lymphoid is however unknown. Using quantitative PCR, we have shown that
      significantly higher concentrations of T. parva DNA are detected in the spleens
      of cattle undergoing severe disease compared to other organs.

PMID- 27890080
TI  - Antibodies against Dictyocaulus viviparus major sperm protein in bulk tank milk:
      Association with clinical appearance, herd management and milk production.
AB  - The objective of this study was to conduct a comprehensive field survey using a
      Dictyocaulus viviparus major sperm protein ELISA on bulk tank milk samples from
      Belgian dairy herds to gain insights in: (1) the sensitivity (Se) and specificity
      (Sp) of the test under field conditions; (2) the value of the test to predict a
      future clinical lungworm outbreak; (3) its associations with milk production
      parameters and (4) its associations with herd management factors. A total of 1248
      herds were sampled, with samplings occurring in the middle ("August") and towards
      the end ("October") of the grazing season. A completed questionnaire on potential
      risk factors and potentially lungworm-induced clinical signs was obtained from
      587 farms and milk production records could be obtained from 343 herds. The
      median (25th-75th percentile) D. viviparus antibody level (ODR) was 0.25 (0.19
      0.31) in "August" and 0.24 (0.19-0.32) in "October". At a threshold of 0.41 ODR,
      the Se and Sp were estimated using mixture models at 50 and 99%, respectively. At
      the same threshold, the positive and negative predictive value of the ELISA
      applied in "August" on the occurrence of farmer-reported lungworm symptoms in the
      period August-November were 65% and 69%, respectively. D. viviparus antibody
      levels were significantly higher in the north vs. the south of the country, in
      large herds and in herds that did not mow pastures or that frequently purchased
      new animals. An increase in the ELISA result of "August" over the interquartile
      range was associated with a drop in the annual average milk yield, milk protein%
      and milk fat% of -0.50kgcow-1day-1, 0.02 and 0.02, respectively. The
      relationships between the ELISA results in "October" and milk production
      parameters were also negative, but lower and non- or only marginally significant.
      We conclude that the bulk tank milk ELISA has a low value to predict lungworm
      disease on an individual farm based on a fixed sampling date in the middle of the
      grazing season. On the other hand, the test has been potential to detect
      subclinical production impacts and study risk factors through epidemiological
      surveys.

PMID- 27890081
TI  - Association between Leishmania infantum DNA in the hair of dogs and their
      infectiousness to Lutzomyia longipalpis.
AB  - Diagnosis of infection with Leishmania infantum by DNA detection in the hair has
      been recently demonstrated in dogs and wild animals. Our objective was to
      investigate if polymerase chain reaction (PCR) in hair might be used to identify
      infectious dogs. Thus, we assessed the infectiousness to Lutzomyia longipalpis by
      xenodiagnosis in comparison with the detection of L. infantum DNA by PCR in the
      hair, and with serology for anti-Leishmania IgG by ELISA in 15 positive dogs for
      L. infantum infection. Eight healthy dogs were included as negative controls.
      Among the 15 infected dogs, 13 were found positive in the ELISA (87%), 12 were
      PCR positive in the hair (80%), and 10 were positive in xenodiagnosis (67%).
      Positivity in the hair was associated with positivity in spleen (p=0.0003),
      seropositivity for antibodies (p=0.0006) and parasite transmission to L.
      longipalpis (p=0.0028). Considering the benefits to animal welfare and
      feasibility of hair sampling method, studies in larger and more diverse
      populations of naturally infected dogs from endemic areas should be conducted to
      evaluate the sensitivity, specificity, and predictive values of PCR using hair as
      a possible biomarker of infectiousness in dogs.

PMID- 27890082
TI  - RAP-1a is the main rhoptry-associated-protein-1 (RAP-1) recognized during
      infection with Babesia sp. BQ1 (Lintan) (B. motasi-like phylogenetic group), a
      pathogen of sheep in China.
AB  - Babesia sp. BQ1 (Lintan) is one of the parasites isolated from infected sheep in
      China that belongs to the B. motasi-like phylogenetic group. The rhoptry
      associated-protein 1 (rap-1) locus in this group consists of a complex
      organization of 12 genes of three main types: 6 rap-1a variants intercalated with
      5 identical copies of rap-1b and a single 3' ending rap-1c gene. In the present
      study, transcription analysis performed by standard RT-PCR demonstrated that the
      three different rap-1 gene types and the four rap-1a variants were transcribed by
      the parasite cultivated in vitro. Peptides, specific for each rap-1 type gene,
      were selected in putative linear B-epitopes and used to raise polyclonal rabbit
      antisera. Using these sera, the same expression pattern of RAP-1 proteins was
      found in parasites cultivated in vitro or collected from acute infection whereas
      only RAP-1a67 was detectable in merozoite extracts. However, ELISA performed with
      recombinant RAP-1a67, RAP-1b or RAP-1c and sera from infected sheep demonstrated
      that RAP-1a67 is the main RAP-1 recognized during infection, even if some
      infected sheep also recognized RAP-1b and/or RAP-1c.

PMID- 27890083
TI  - Anticoccidial efficacy of naringenin and a grapefruit peel extract in growing
      lambs naturally-infected with Eimeria spp.
AB  - The current study aimed to determine the anti-Eimeria efficacy of an extract of
      grapefruit peels (GF) and commercial naringenin (NAR) in naturally-infected
      lambs, as well as the influence of these flavonoids on the oxidative status
      during ovine coccidiosis. Pharmacokinetic profiles were also determined. Extracts
      were administered per os to Eimeria naturally infected growing lambs during 90
      consecutive days. The commercial anticoccidial drug toltrazuril (TTZ) was
      included in this trial as a standard. Twenty-four lambs were divided into four
      groups: NAR, lambs given a daily dose of 5mg of a commercial naringenin extract
      of 98% higher purity per kg body weight; GF, lambs that recived a daily dose of
      5mg of ethanolic extract of grapefruit peels per kg body weight; TTZ, lambs
      treated with 20mg of toltrazuril/kg body weight on days 0 and 15 of the
      experiment; and CTRL, untreated lambs that received daily dose of 30ml of water.
      Daily doses of GF and NAR were dissolved in 30ml of water and orally given to
      animals; whereas toltrazuril was administered as a single dose of an undiluted
      suspension to lambs of the TTZ group. The CTRL group received 30ml of water; as
      well as the TTZ group for the period after the single dose administration. Fecal
      and serum samples were collected from all lambs. Anticoccidial efficacy was
      estimated by coprological techniques. Generation of nitric oxide levels and the
      antioxidant capacity of the experimental compounds were determined by the Griess
      and ABTS assays, respectively. The pharmacokinetic parameters of NAR and the GF
      extract were obtained. On day 30 post-ingestion, anticoccidial efficacy was
      91.76% (NAR) and 89.65% (GF); whereas 99.63% of efficacy was achieved with TTZ
      15days after treatment. NAR, GF and TTZ significantly reduced oxidative stress in
      infected animals. The mean daily weight gain for each group was 122g (NAR), 122g
      (GF), 143g (TTZ) and 98g (CTRL). Following the oral administration of NAR and GF,
      values in plasma approached maximum concentrations within 2.1 to 2.5h. In
      conclusion, the administration of NAR and the GF extract reduced Eimeria oocyst
      output, oxidative stress and promoted higher mean daily weight gains in infected
      lambs.

PMID- 27890084
TI  - Comparison of molecular and conventional methods for the diagnosis of Fasciola
      hepatica infection in the field.
AB  - The liver fluke, Fasciola hepatica, is one of the major parasite threats to
      livestock industries world-wide. In sheep and cattle, F. hepatica infection is
      commonly diagnosed using a range of methods. Aside from conventional coprological
      and serological diagnostic methods, there are also several molecular methods
      available based on the detection of liver fluke DNA in faeces. In this study, the
      outcomes of faecal egg count (FEC), serology and coproantigen ELISA (cELISA) were
      compared with the performance of polymerase chain reaction (PCR) and loop
      mediated isothermal amplification (LAMP) in diagnosis of F. hepatica from
      naturally infected cattle and sheep. A total of 64 individual faecal and serum
      samples were collected from four sheep and beef cattle herds with previous
      histories of F. hepatica infection. FEC and coproantigen levels were measured in
      faecal samples and anti-F.hepatica antibody levels were measured in serum
      samples. DNA samples isolated from faeces were examined both by PCR and LAMP,
      targeting the internal transcribed spacer 2 (ITS2) region of the F. hepatica
      genome. Results showed that F. hepatica eggs were present in 28 animals, while
      coproantigen and specific anti-F. hepatica antibodies were detected in 36 and 53
      animals, respectively. Only 3 and 6 samples were positive by PCR and LAMP,
      respectively. To calculate method specificity and sensitivity, a combination of
      FEC and cELISA was selected as the composite reference standard (CRS). When
      compared to the CRS, PCR had a sensitivity of 10.7% and specificity of 100%,
      whereas LAMP had a sensitivity and specificity of 17.9% and 97.2%, respectively.
      PCR and LAMP in this field study were highly specific, but both had poor
      sensitivity compared with FEC and cELISA. Potential reasons for PCR and LAMP
      failure were inadequate amounts of amplifiable F. hepatica DNA, possibly due to
      the choice of DNA extraction procedure, amount of faecal material processed, as
      well as different faeces consistency and composition between different animal
      species.

PMID- 27890085
TI  - Detection of N2O-producing fungi in environment using nitrite reductase gene
      (nirK)-targeting primers.
AB  - Fungal denitrification has been increasingly investigated, but its community
      ecology is poorly understood due to the lack of culture-independent tools. In
      this work, four pairs of nirK-targeting primers were designed and evaluated for
      primer specificity and efficiency using thirty N2O-producing fungal cultures and
      an agricultural soil. All primers amplified nirK from fungi and soil, but their
      efficiency and specificity were different. A primer set, FnirK_F3/R2 amplified
      ~80 % of tested fungi, including Aspergillus, Fusarium, Penicillium, and
      Trichoderma, as compared to ~40-70 % for other three primers. The nirK fragments
      of fungal and soil DNA amplified by FnirK_F3/R2 were phylogenetically related to
      denitrifying fungi in the orders Eurotiales, Hypocreales, and Sordariales; and
      clone sequences were also distributed in the clusters of Chaetomium, Metarhizium,
      and Myceliophthora that were uncultured from soil in our previous work. This
      proved the wide-range capability of primers for amplifying diverse denitrifying
      fungi from environment. However, our primers and recently-developed other primers
      amplified bacterial nirK from soil and this co-amplification of fungal and
      bacterial nirK was theoretically discussed. The FnirK_F3/R2 was further compared
      with published primers; results from clone libraries demonstrated that
      FnirK_F3/R2 was more specifically targeted on fungi and had broader taxonomical
      coverage than some others.

PMID- 27890086
TI  - Multiple isoforms for the catalytic subunit of PKA in the basal fungal lineage
      Mucor circinelloides.
AB  - Protein kinase A (PKA) activity is involved in dimorphism of the basal fungal
      lineage Mucor. From the recently sequenced genome of Mucor circinelloides we
      could predict ten catalytic subunits of PKA. From sequence alignment and
      structural prediction we conclude that the catalytic core of the isoforms is
      conserved, and the difference between them resides in their amino termini. This
      high number of isoforms is maintained in the subdivision Mucoromycotina. Each
      paralogue, when compared to the ones form other fungi is more homologous to one
      of its orthologs than to its paralogs. All of these fungal isoforms cannot be
      included in the class I or II in which fungal protein kinases have been
      classified. mRNA levels for each isoform were measured during aerobic and
      anaerobic growth. The expression of each isoform is differential and associated
      to a particular growth stage. We reanalyzed the sequence of PKAC (GI 20218944),
      the only cloned sequence available until now for a catalytic subunit of M.
      circinelloides. PKAC cannot be classified as a PKA because of its difference in
      the conserved C-tail; it shares with PKB a conserved C2 domain in the N-terminus.
      No catalytic activity could be measured for this protein nor predicted
      bioinformatically. It can thus be classified as a pseudokinase. Its importance
      can not be underestimated since it is expressed at the mRNA level in different
      stages of growth, and its deletion is lethal.

PMID- 27890087
TI  - Molecular phylogeny, diversity, community structure, and plant growth promoting
      properties of fungal endophytes associated with the corms of saffron plant: An
      insight into the microbiome of Crocus sativus Linn.
AB  - A total of 294 fungal endophytes were isolated from the corms of Crocus sativus
      at two stages of crocus life cycle collected from 14 different saffron growing
      sites in Jammu and Kashmir (J & K) State, India. Molecular phylogeny assigned
      them into 36 distinct internal transcribed spacer (ITS) genotypes which spread
      over 19 genera. The diversity of endophytes was higher at the dormant than at the
      vegetative stage. The Saffron microbiome was dominated by Phialophora mustea and
      Cadophora malorum, both are dark septate endophytes (DSEs). Some endophytes were
      found to possess antimicrobial properties that could be helpful for the host in
      evading the pathogens. These endophytes generally produced significant quantities
      of indole acetic acid (IAA) as well. However, thirteen of the endophytic taxa
      were found to cause corm rot in the host with different levels of severity under
      in vitro as well as in vivo conditions. This is the first report of community
      structure and biological properties of fungal endophytes associated with C.
      sativus, which may eventually help us to develop agro-technologies, based on
      plant-endophyte interactions for sustainable cultivation of saffron. The
      endophytes preserved ex situ, in this study, may also yield bioactive natural
      products for pharmacological and industrial applications.

PMID- 27890089
TI  - A mid-Cretaceous Eccrinales infesting a primitive wasp in Myanmar amber.
AB  - A mid-Cretaceous Eccrinales in Myanmar amber is described as Paleocadus
      burmiticus gen. et sp. nov. in the family Eccrinaceae. The fossil is represented
      by two types of sporangiospores formed on different thalli protruding from the
      anus of a primitive wasp, with secondary infestation spores multinucleate and
      thin walled. Its presence establishes the Eccrinales in the mid-Cretaceous and
      shows that at that time, lineages of this group parasitized wasps, an association
      unknown with extant members of the Order.

PMID- 27890088
TI  - Fungal endophytic communities associated to the phyllosphere of grapevine
      cultivars under different types of management.
AB  - Fungal endophytes present in different asymptomatic grapevine plants (Vitis
      vinifera L.) located in different vineyards within Alentejo, a highly important
      viticulture region in Portugal, were identified in this study. Sampled grapevine
      plants included the three most representative cultivars in the region, Syrah,
      Cabernet Sauvignon, and Aragonez, growing under two different modes of
      management, conventional and biological. Sixteen fungal taxa were identified
      through sequencing of the internal transcribed spacer region. Total number of
      endophytic fungi isolated showed significant differences both in management mode
      and in cultivars, with higher numbers in grapevines under conventional mode and
      from Syrah cultivar. The composition of fungal endophytic communities did not
      show significant differences among cultivars, but differences were observed
      between fungal communities isolated from grapevines under biological or
      conventional modes. The most fungal taxa isolated from grapevines cultivated
      under biological mode were Alternaria alternata, Cladosporium sp., and Nigrospora
      oryzae, and under conventional mode Botrytis cinerea, Epicoccum nigrum, and
      Epicoccum sp. These differences suggest that the different products used in
      grapevine production have impacts in fungal endophytic composition. Further
      investigation of the identified fungi with respect to their antagonistic
      characteristics and potential use in plant protection to ensure food safety is
      now in course.

PMID- 27890090
TI  - Guyanagarika, a new ectomycorrhizal genus of Agaricales from the Neotropics.
AB  - A new genus and three new species of Agaricales are described from the Pakaraima
      Mountains of Guyana in the central Guiana Shield. All three of these new species
      fruit on the ground in association with species of the ectomycorrhizal (ECM) tree
      genus Dicymbe (Fabaceae subfam. Caesalpinioideae) and one species has been shown
      to form ectomycorrhizas. Multi-locus molecular phylogenetic analyses place
      Guyanagarika gen. nov. within the Catathelasma clade, a lineage in the suborder
      Tricholomatineae of the Agaricales. We formally recognize this 'Catathelasma
      clade' as an expanded family Catathelasmataceae that includes the genera
      Callistosporium, Catathelasma, Guyanagarika, Macrocybe, Pleurocollybia, and
      Pseudolaccaria. Within the Catathelasmataceae, Catathelasma and Guyanagarika
      represent independent origins of the ectomycorrhizal habit. Guyanagarika is the
      first documented case of an ECM Agaricales genus known only from the Neotropics.

PMID- 27890091
TI  - Lactarius subgenus Russularia (Basidiomycota, Russulales): novel Asian species,
      worldwide phylogeny and evolutionary relationships.
AB  - Lactarius subg. Russularia is a large group of milkcaps occurring almost
      worldwide and dominant in many ecosystems. In this study we focus on new
      diversity, evolutionary relationships, divergence time, and origin of the
      subgenus. Six conifer symbionts are described as new to science: Lactarius atrii,
      L. aurantionitidus, L. dombangensis, L. flavigalactus, L. lachungensis, and L.
      sikkimensis. Species delimitation is assessed based on the concordance between
      morphological characteristics and an ITS phylogeny. Infrageneric relationships
      were studied using a phylogeny constructed from concatenated ITS-rpb2 data using
      Maximum Likelihood and Bayesian inference. Results show that species in this
      subgenus do not cluster together according to their geographic origin.
      Intercontinental sister relationships between Europe/Asia/North America are
      common but actual conspecificity is rare. This result suggests that allopatric
      speciation has played an important role within this subgenus. Only few
      morphological characteristics tend to be phylogenetically informative, with the
      most important being presence or absence of true cystidia and the pileipellis
      structure. Two datasets were generated in order to estimate the age of L. subg.
      Russularia. The results suggest the origin of L. subg. Russularia to be in the
      Mid Miocene period.

PMID- 27890092
TI  - Routes of phlogopite weathering by three fungal strains.
AB  - Fungi dissolve soil minerals by acidification and mechanical disruption.
      Dissolution may occur at the microscale (contact between fungus and mineral) and
      medium scale (entire mineral grains). Mineral weathering by fungi and other
      microorganisms is thought to be of significant global contribution, perhaps
      producing specific weathering signatures. We report fungal dissolution of
      phlogopite mica in experiments with three fungal strains (Alternaria tenuissima,
      Cladosporium cladosporioides, Stilbella sp.) on solid medium for 30 days at 21 
      degrees C and 96-100% relative humidity. The study used variable-pressure SEM-EDS
      equipped with charge contrast imaging. Statistical analysis of the results
      discriminated between the weathering activities of the three fungal species,
      which increased from Stilbella sp. to C. cladosporioides to A. tenuissima, in
      agreement with the respective decreasing pH in the media (6.4, 5.8, 5.2 +/-
      0.03). Phlogopite weathering features were irregular and variable, apparently not
      caused by direct contact with fungal hyphae. EDS values indicated two or more
      dissolution mechanisms, one of them suggesting cation rearrangement in the mica
      towards formation of Al-rich smectite. Intimate fungus-mineral interaction was
      observed, and the lack of observable dissolution traces from such contact
      interaction is interpreted as the result of effacing by the more intense acid
      leaching operating at larger scale.

PMID- 27890093
TI  - 3-Nitropropionic acid production by the endophytic Diaporthe citri: Molecular
      taxonomy, chemical characterization, and quantification under pH variation.
AB  - 3-nitropropionic acid (3-NPA) is a nitrogenated compound produced by plants and
      fungi and has been associated with poisoning episodes in humans, animals, and to
      induction of Huntington disease symptoms in rats. The production of 3-NPA by
      endophytes has been reported, but the function and biosynthesis are not well
      defined. The specie of endophytic strain G-01 was confirmed as Diaporthe citri
      using a multilocus sequence analysis, and was verified different concentrations
      of 3-NPA produced at different initial pHs by these strain. The chemical analysis
      indicated that 3-NPA was the majority compound present in the crude extracts. The
      better extraction condition was at an initial pH of 7.0 for 22 d, yielding about
      80 % of 3-NPA per mg of extract. It was observed that the concentration of 3-NPA
      increased after the initial consumption of reduction sugars, indicating that the
      compound is produced after the high energetic production phase of the fungus.
      These and other studies demonstrate the production of this compound by plants and
      endophytic fungi, indicating that 3-NPA may be involved in defence and nutrition
      systems of endophytes and host plants, and they also might participate in the
      biogeochemical nitrogen cycle.

PMID- 27890094
TI  - Functional expression, production, and biochemical characterization of a laccase
      using yeast surface display technology.
AB  - A Trametes versicolor laccase was functionally expressed on the membrane surface
      of Saccharomyces cerevisiae EBY100. Laccase expression was increased 6.57-fold by
      medium optimization and surpassed production by the native strain. Maximal
      laccase and biomass production reached 19 735 +/- 1719 Ug-1 and 6.22 +/- 0.53 gL
      1 respectively, after 2 d of culture. Optimum oxidization of all substrates by
      laccase was observed at pH 3. Laccase showed high affinity towards substrates
      used with Km (mM) and Vmax (MUmol min-1) values of 0.57 +/- 0.0047 and 24.55 +/-
      0.64, 1.52 +/- 0.52 and 9.25 +/- 1.78, and 2.67 +/- 0.12 and 11.26 +/- 0.75, were
      reported for ABTS, 2, 6-DMP and GUA, respectively. EDTA and NaN3 displayed none
      competitive inhibition towards laccase activity. The optimum temperature for
      activity was 50  degrees C; however, the enzyme was stable over a wide range of
      temperatures (25-70  degrees C). The biologically immobilized laccase showed high
      reusability towards phenolic substrates and low reusability with non-phenolic
      substrates. High affinity for a diversity phenolic compounds and great ethanol
      tolerance substantiates this laccase/yeast biocatalyst potential for application
      in the production of bioethanol.

PMID- 27890095
TI  - An unexpected death due to massive ascites and a giant mucinous ovarian
      cystadenoma.
AB  - A female in her thirties fell face down in her room. She was motionless when her
      sister found her. She was transported to the hospital by ambulance and was in a
      state of cardiopulmonary arrest on admission. She did not respond to
      resuscitation. Her abdomen had started to swell 3years before her death. An
      autopsy was performed to clarify the decedent's cause of death. She was 172cm
      tall and weighed 146kg. Her maximum abdominal girth was 172.1cm. A subcutaneous
      hemorrhage measuring 4.5cm in diameter was observed in the epigastric region. The
      abdominal cavity contained brownish ascites (54.1L). The left ovary was markedly
      swollen, and the combined weight of the uterus and right ovary was more than
      13.0kg. A left ovarian tumor consisting of serous and mucinous cysts was
      detected. There were no metastatic lesions in the peritoneum or other organs. She
      might have suffered circulatory disturbance caused by the ascites and ovarian
      tumor. Moreover, being in a prone position would have resulted in an increase in
      intra-abdominal pressure, further exacerbating her circulatory problems.
      Therefore, her cause of death was considered to be circulatory failure caused by
      significant ascites and a large ovarian tumor.

PMID- 27890096
TI  - Entrance and exit wounds of high velocity bullet: An autopsy analysis in the
      event of dispersing the mass rally in Bangkok Thailand, May 2010.
AB  - Fatal mass casualties by high velocity bullets (HVBs) are rare events in peaceful
      countries. This study presents 27 forensic autopsy cases with 32 shots fired by
      5.56*45mm. HVB (M-16 rifle bullets) during the dispersing the mass rally in
      Bangkok Thailand, May 2010. It was found that twenty-three (71.88%) typical
      entrance HVB wounds had round sizes less than the bullet diameters. Most entrance
      wounds had microtears but no collar abrasion since a HVB has a small streamlined
      spitzer tip and full metal jacket. For exit wounds, there were various sizes and
      shapes depending on which section of wound ballistics presented when the bullet
      exited the body. If a bullet exited in the section of temporally cavity
      formation, there would be a large size exit wound in accordance with the degree
      of bullet yaw. This is different from civilian bullets whereby the shape looks
      like a cylindrical round nose and at low velocity that causes entrance wounds
      with a similar size to the bullet diameter and is usually round or oval shape
      with collar abrasion. The temporary cavity is not as large as in a HVB so exit
      wounds are not quite as large and present a ragged border compared to a HVB. We
      also reported 9 out of 32 shots (28.13%) of atypical entrance wounds that had
      various characteristics depending on site of injury and destabilization of
      bullets. These findings may be helpful to forensic pathologists and to give
      physicians, who need to diagnose HVB wounds, more confidence.

PMID- 27890097
TI  - Forensic genetic study of 29 Y-STRs in Korean population.
AB  - In this study, we compared two recently released commercial Y-chromosomal short
      tandem repeat (Y-STR) kits: the PowerPlex Y23 System (PPY23) and Yfiler(r) Plus
      PCR amplification kit (YPlus). We performed validation studies, including
      sensitivity, tolerance to PCR inhibitors, and mixture analysis, and a population
      genetics study using 306 unrelated South Korean males. PPY23 and YPlus showed
      similar sensitivity, but PPY23 showed higher tolerance to humic acid than YPlus.
      Furthermore, the detection rate of unique minor alleles called from male/male
      mixtures was higher for PPY23 than for YPlus. Comparing the newly added loci, the
      mean values of gene diversity for PPY23 and YPlus were 0.6715 and 0.8158,
      respectively. The discrimination capacity in the 306 unrelated South Korean males
      for PPY23 was 0.9837, and that for YPlus was 0.9935. These results will inform
      the selection of suitable Y-STR kits based on the purpose of forensic DNA
      analysis.

PMID- 27890098
TI  - Ballistics and anatomical modelling - A review.
AB  - Ballistics is the study of a projectiles motion and can be broken down into four
      stages: internal, intermediate, external and terminal ballistics. The study of
      the effects a projectile has on a living tissue is referred to as wound
      ballistics and falls within terminal ballistics. To understand the effects a
      projectile has on living tissues the mechanisms of wounding need to be
      understood. These include the permanent and temporary cavities, energy, yawing,
      tumbling and fragmenting. Much ballistics research has been conducted including
      using cadavers, animal models and simulants such as ballistics ordnance gelatine.
      Further research is being conducted into developing anatomical, 3D, experimental
      and computational models. However, these models need to accurately represent the
      human body and its heterogeneous nature which involves understanding the
      biomechanical properties of the different tissues and organs. Further research is
      needed to accurately represent the human tissues with simulants and is slowly
      being conducted.

PMID- 27890099
TI  - Potential use of pericardial cTnI, Mg2+ and Ca2+ in the forensic investigation of
      seawater drowning in Greece: An initial assessment.
AB  - The investigation of drowning constitutes one of the biggest problems in forensic
      practice. Elevated cardiac troponin I (cTnI) levels in biological fluids have
      been associated with myocardial damage, whereas increased Mg2+ and Ca2+ levels
      were found in cases of seawater drowning. The aim of this study was to examine
      the diagnostic utility of postmortem determination of cTnI, Mg2+ and Ca2+ in the
      pericardial fluid, in differentiating between cases of seawater drowning related
      to myocardial injury and those brought about by other causes. This study included
      76 cases selected during a 2-year period from medicolegal autopsies. The cases
      were divided into three groups, according to the cause of death established based
      on macroscopic and microscopic evidence. The groups were: 1) seawater drowning
      (n=23), 2) seawater drowning with histological evidence of myocardial infarction
      (n=28), and 3) myocardial infarction unrelated to drowning (n=25). cTnI was
      determined with an enzyme immunoassay; Mg2+ and Ca2+ with standard colorimetric
      assays. Pericardial cTnI levels were significantly lower in group 1 compared to
      groups 2 and 3. In contrast, pericardial Mg2+ and Ca2+ levels were both
      significantly higher in groups 1 and 2 compared to group 3. Our results suggest
      that the postmortem determination of pericardial cTnI levels may be useful in
      detecting previous myocardial damage as a contributory factor in death from
      seawater drowning and provide independent confirmation of the usefulness of
      pericardial Mg2+ and Ca2+ levels for differentiating between seawater drowning
      and fatal acute myocardial injury unrelated to the former.

PMID- 27890100
TI  - Sex and ancestry assessment of Brazilian crania using semi-automatic mesh
      processing tools.
AB  - The present paper aims to test performances of semi-automatic tools for mesh-to
      mesh processing while assessing sex and ancestry in documented human crania. The
      studied sample of 80 human crania, which originated in two documented Brazilian
      collections (Sao Paulo, Brazil) was digitized using photogrammetry and laser
      scanning. 3D cranial morphology was quantified by computing inter-mesh
      dissimilarity measures using in-house freeware FIDENTIS Analyst
      (www.fidentis.com). Numerical outputs were further processed using Discriminant
      Function Analysis and Canonical Variant Analysis in order to classify models into
      sex and ancestry groups. In addition, cranial morphology was described by a set
      of 37 landmarks, processed by a Procrustes analysis and confronted with the inter
      mesh comparison. Patterns of sexual dimorphism and ancestral group-specific
      variation were interpreted using average meshes and further emphasized by
      employing advanced visualization graphics. The mesh-to-mesh processing was
      capable to detect shape differences related to sex and ancestry. The highest
      accuracy levels for sex determination were obtained for meshes representing the
      facial skeleton and the supraorbital region. For both, analysis correctly
      assigned 82.5% of the crania. Ancestry-related differences were manifested
      primarily in the global cranial features (observed accuracy rates reaching 63%).
      The advanced visualization tools provided a highly informative insight into
      sexual dimorphism and ancestry-related variation. While in the current state the
      technique cannot be considered suitable for being implemented into the everyday
      forensic practice, the extent of automatization proved to be perspective,
      especially for assessing skeletal features that cannot be properly quantified
      using discrete variables.

PMID- 27890101
TI  - Genetic polymorphism studies on 22 autosomal STR loci of the PowerPlex Fusion
      System in Bangladeshi population.
AB  - Genetic polymorphism of 22 autosomal STR loci included in PowerPlex(r) Fusion
      System (D3S1358, D1S1656, D2S441, D10S1248, D13S317, Penta E, D16S539, D18S51,
      D2S1338, CSF1PO, Penta D, TH01, vWA, D21S11, D7S820, D5S818, TPOX, D8S1179,
      D12S391, D19S433, FGA and D22S1045) was studied in 188 unrelated Bangladeshi
      Bengali individuals. Allele frequencies and forensic efficiency parameters such
      as, the power of discrimination (PD), observed and expected heterozygosity (Ho &
      He), polymorphism information content (PIC), probability of match (PM), power of
      exclusion (PE) and typical paternity index was calculated for the loci. The
      combined PM and PE for all 22 STR loci were calculated to be 5.29*10-27 and
      0.99999999945 respectively. The dataset indicated the usefulness of these loci in
      personal identification, parentage testing and complex kinship analysis in
      Bangladeshi population. A neighbor-joining tree was constructed based on pair
      wise Nei's genetic distance by comparing allele frequency data for the 22 loci
      with six other populations. The analysis showed that Bangladeshi population lies
      closer to a clade consisting Japan, the Philippines and East Timot populations.

PMID- 27890102
TI  - Comment on sudden death due to rupture of the right internal carotid artery in
      neurofibromatosis type 1 by Liang et al.

PMID- 27890103
TI  - The genetic structure of native Americans in North America based on the
      Globalfiler(r) STRs.
AB  - Current forensic STR databases, such as CODIS, lack population genetic data on
      Native American populations. Information from a geographically diverse array of
      tribes is necessary to provide improved statistical estimates of the strength of
      associations with DNA evidence. The Globalfiler(r) STR markers were used to
      characterize the genetic structure of ten tribal populations from seven
      geographic regions in North America, including those not presently represented in
      forensic databases. Samples from the Arctic region, Baja California,
      California/Great Basin, the Southeast, Mexico, the Midwest, and the Southwest
      were analyzed for allele frequencies, observed and expected heterozygosities, and
      F-statistics. The tribal samples exhibited an FST or theta value above the
      conservative 0.03 estimate recommended by the National Research Council (NRC) for
      calculating random match probabilities among Native Americans. The greater
      differentiation among tribal populations computed here (theta=0.04) warrants the
      inclusion of additional regional Native American samples into STR databases.

PMID- 27890104
TI  - An autopsy case of spontaneous esophageal perforation (Boerhaave syndrome).
AB  - A 45-year-old male, an alcohol addict with asthma, was found dead in his home,
      after several days of continued drinking. A forensic autopsy was performed 3days
      after the discovery of his death in order to specify the cause of death. A
      longitudinal perforation penetrating all layers of the esophagus measuring 1.8cm
      was present on the left wall approximately 2.0cm from the gastroesophageal
      junction. There were 1900mL of greenish to brownish turbid liquid in the left
      pleural cavity and 150mL of greenish viscous liquid in the stomach.
      Histopathologically, an infiltration of numerous neutrophils was evident in the
      submucosa layer, proper muscular layer, and serous membrane of the esophagus,
      corresponding to the esophageal laceration. The serum C-reactive protein (CRP)
      concentration was determined to be 3.1mg/dL. The alcohol concentrations were
      determined to be 1.49mg/g in the right cardiac blood, 1.31mg/g in the left
      cardiac blood, and 2.48mg/g in urine. Based upon the autopsy and
      histopathological findings, as well as the biochemical and toxicological
      analyses, we concluded that the cause of death was respiratory failure by pleural
      effusion, resulting from spontaneous esophageal perforation. This was the first
      report of a spontaneous esophageal perforation eventually causing respiratory
      failure.

PMID- 27890105
TI  - Use of postmortem computed tomography angiography to detect vascular injuries
      accompanying skull base fracture.
AB  - A 58-year-old woman who had presented for upper gastrointestinal barium
      examination accidently slipped from the movable bed, and her head became
      compressed between the end of the bed and the side wall. She suffered massive
      bleeding from her nose and ear followed by cardiac arrest, and subsequent
      attempts at cardiopulmonary resuscitation failed. A medicolegal autopsy was
      performed to reveal the cause of death, as part of the investigation of the
      accident. During the autopsy, postmortem cerebral CT angiography was carried out
      by injection of 5% gelatin-barium emulsion as a radiopaque contrast medium into
      the bilateral common carotid arteries, demonstrating transudation of the contrast
      medium into the right acoustic meatus and the sphenoidal sinus cavity.
      Considering that the body appeared anemic and that PMCTA suggested vascular
      injuries, the cause of death was definitively determined to be hemorrhagic shock
      due to injuries to the right internal carotid artery, accompanied by skull base
      fracture. Postmortem CT angiography played an important role in confirming that
      the vascular injuries had been responsible for the bleeding, as the lesions could
      not be fully confirmed by native CT or macroscopic examination.

PMID- 27890106
TI  - Study on the criteria for assessing skull-face correspondence in craniofacial
      superimposition.
AB  - Craniofacial superimposition has the potential to be used as an identification
      method when other traditional biological techniques are not applicable due to
      insufficient quality or absence of ante-mortem and post-mortem data. Despite
      having been used in many countries as a method of inclusion and exclusion for
      over a century it lacks standards. Thus, the purpose of this research is to
      provide forensic practitioners with standard criteria for analysing skull-face
      relationships. Thirty-seven experts from 16 different institutions participated
      in this study, which consisted of evaluating 65 criteria for assessing skull-face
      anatomical consistency on a sample of 24 different skull-face superimpositions.
      An unbiased statistical analysis established the most objective and
      discriminative criteria. Results did not show strong associations, however,
      important insights to address lack of standards were provided. In addition, a
      novel methodology for understanding and standardizing identification methods
      based on the observation of morphological patterns has been proposed.

PMID- 27890107
TI  - An analysis of causative factors in closed criminal medical malpractice cases of
      the Taiwan Supreme Court: 2000-2014.
AB  - Most medical malpractice in Taiwan leads to criminal prosecution. This study
      examined the epidemiologic factors and clinical errors that led to medical
      malpractice convictions in Taiwanese criminal prosecutions. A retrospective, 15
      year population-based review of criminal Supreme Court judgments pertaining to
      medical malpractice against physicians and nurses was conducted. Eighty-four
      cases were reviewed, yielding data that included the number and specialty
      involved, accused hospitals, the diagnosis, the time interval between incidents
      to closure, result of adjudication, the origin of cases (private vs. public
      prosecution), the result of medical appraisal, and the primary error. Overall,
      the cases averaged 7.6years to achieve final adjudication. Seventy-five percent
      were settled in favor of the clinician; twenty-three physicians and three nurses
      were found guilty, but all of these avoided imprisonment via probation or
      replacement with forfeit. The single most risky specialty was emergency medicine
      (22.6% of the cases), with 36.8% of those resulting in guilty verdicts. The most
      common diagnosis groups were infectious diseases (23.8%), intracranial
      hemorrhages (10.7%), and acute coronary syndrome (9.5%). Public prosecutions had
      a 41.2% conviction rate; no guilty verdicts resulted from private prosecution.
      Nineteen (22.6%) cases were commuted, and 73.7% of those had a controversial
      appraisal result. The characteristics of criminal malpractice prosecution in
      Taiwan that could be improved to relieve the stress of frivolous lawsuits on the
      judicial process include lengthy jurisdiction process; low public-prosecution
      conviction rate; frequent commuted jurisdiction related to a controversial
      appraisal; and zero imprisonment rate for clinicians.

PMID- 27890108
TI  - Gastric excretion of intravenously administered drugs in critical care patients.

PMID- 27890109
TI  - Ascorbic acid and vitamin C-containing beverages delay the leucomalachite green
      reaction to detect latent bloodstains.
AB  - The leucomalachite green (LMG) test is one of catalytic tests for the detection
      of latent bloodstains and generally used in forensic field because of convenience
      and cost/time-effectiveness. However, contamination of latent bloodstains at
      crime scenes can interfere with the LMG reaction, resulting in false-negative or
      false-positive decisions. Herein, we examined if ascorbic acid and vitamin C (l
      ascorbic acid or ascorbate)-containing beverages affect the LMG reaction.
      Ascorbic acid showed the inhibitory activities on the LMG reaction in a dose
      dependent manner. Similarly, vitamin C-containing beverages also inhibited the
      LMG reaction and the inhibitory effects were proportional to the concentrations
      of vitamin C in beverages. It was also identified that as incubation time after
      adding LMG reagent to the mixtures of blood and ascorbic acid or beverages was
      increased, the inhibitory effects of ascorbic acid vitamin C-containing beverages
      on LMG test were disappeared. These results suggest that the LMG reaction is
      delayed but not stopped by ascorbic acid and vitamin C-containing beverages.
      Neither incubation at room temperature around 20-25 degrees C nor the addition of
      acetic acid affects the inhibitory activity of ascorbic acid on LMG reaction. We
      also showed that ascorbic acid does not affect DNA stability, allowing us to
      obtain full short tandem repeat (STR) profiles through amplification of DNA using
      commercial STR kits. In conclusion, ascorbic acid and vitamin C-containing
      beverages delayed the LMG reaction, suggesting that it should be considered that
      negative results of LMG test could be false negative due to contamination of
      bloodstains with inhibitory factors on LMG test.

PMID- 27890110
TI  - Is the diagnosis of anaphylaxis reliable in forensics? The role of beta-tryptase
      and its correct interpretation.

PMID- 27890111
TI  - Sex estimation of the tibia in modern Turkish: A computed tomography study.
AB  - The utilization of computed tomography is beneficial for the analysis of skeletal
      remains and it has important advantages for anthropometric studies. The present
      study investigated morphometry of left tibia using CT images of a contemporary
      Turkish population. Seven parameters were measured on 203 individuals (124 males
      and 79 females) within the 19-92-years age group. The first objective of this
      study was to provide population-specific sex estimation equations for the
      contemporary Turkish population based on CT images. A second objective was to
      test the sex estimation formulae on Southern Europeans by Kranioti and Apostol
      (2015). Univariate discriminant functions resulted in classification accuracy
      that ranged from 66 to 86%. The best single variable was found to be upper
      epiphyseal breadth (86%) followed by lower epiphyseal breadth (85%). Multivariate
      discriminant functions resulted in classification accuracy for cross-validated
      data ranged from 79 to 86%. Applying the multivariate sex estimation formulae on
      Southern Europeans (SE) by Kranioti and Apostol in our sample resulted in very
      high classification accuracy ranging from 81 to 88%. In addition, 35.5-47% of the
      total Turkish sample is correctly classified with over 95% posterior probability,
      which is actually higher than the one reported for the original sample (25-43%).
      We conclude that the tibia is a very useful bone for sex estimation in the
      contemporary Turkish population. Moreover, our test results support the
      hypothesis that the SE formulae are sufficient for the contemporary Turkish
      population and they can be used safely for criminal investigations when posterior
      probabilities are over 95%.

PMID- 27890112
TI  - An autopsy case of prolonged asphyxial death caused by the impacted denture in
      the esophagus.
AB  - A foreign body impacted in the esophagus is not a rare incident among adults or
      children. In adults, a dental prosthesis is prone to become impacted in the
      esophagus. The diagnostic difficulty of this often causes a delay in its removal,
      which can lead to serious complications, including death. This report describes
      the autopsy case of a man who died of prolonged asphyxiation induced by the
      delayed removal of an impacted denture, which was misdiagnosed on his first visit
      notwithstanding that a part of the denture could be seen on X-rays. Cases in
      which an impacted denture led to death have rarely been reported in contrast to
      numerous papers about recovered cases.

PMID- 27890114
TI  - Editorial, Special Issue BBBB.

PMID- 27890113
TI  - MEPROCS framework for Craniofacial Superimposition: Validation study.
AB  - Craniofacial Superimposition (CFS) involves the process of overlaying a skull
      with a number of ante-mortem images of an individual and the analysis of their
      morphological correspondence. The lack of unified working protocols and the
      absence of commonly accepted standards, led to contradictory consensus regarding
      its reliability. One of the more important aims of 'New Methodologies and
      Protocols of Forensic Identification by Craniofacial Superimposition (MEPROCS)'
      project was to propose a common framework for CFS, what can be considered the
      first international standard in the field. The framework aimed to serve as a
      roadmap for avoiding particular assumptions that could bias the process. At the
      same time, it provides some empirical support to certain practices, technological
      means, and morphological criteria expected to facilitate the application of the
      CFS task and to improve its reliability. In order to confirm the utility and
      potential benefits of the framework use, there is a need to empirically evaluate
      it in CFS identification scenarios as close as possible to the reality. Thus, the
      purpose of this study is to validate the CFS framework developed. For that aim 12
      participants were asked to report about a variable number of CFS following all
      the recommendations of the framework. The results are analysed and discussed
      according to the framework understanding and fulfilment, the participants'
      performance, and the correlation between expected decisions and those given by
      the participants. In view of the quantitative results and qualitative examination
      criteria we can conclude that those who follow the MEPROCS recommendations
      improve their performance.

PMID- 27890115
TI  - Letter to the Editor: Hypoxia inducible factor 1alpha: A critical factor for the
      immune response to pathogens and Leishmania.

PMID- 27890116
TI  - Forms of work organization and associations with shoulder disorders: Results from
      a French working population.
AB  - The aim of this study was to identify forms of work organization in a French
      region and to study associations with the occurrence of symptomatic and
      clinically diagnosed shoulder disorders in workers. Workers were randomly
      included in this cross-sectional study from 2002 to 2005. Sixteen organizational
      variables were assessed by a self-administered questionnaire: i.e. shift work,
      job rotation, repetitiveness of tasks, paced work/automatic rate, work pace
      dependent on quantified targets, permanent controls or surveillance, colleagues'
      work and customer demand, and eight variables measuring decision latitude. Five
      forms of work organization were identified using hierarchical cluster analysis
      (HCA) of variables and HCA of workers: low decision latitude with pace
      constraints, medium decision latitude with pace constraints, low decision
      latitude with low pace constraints, high decision latitude with pace constraints
      and high decision latitude with low pace constraints. There were significant
      associations between forms of work organization and symptomatic and clinically
      diagnosed shoulder disorders.

PMID- 27890117
TI  - Latent error detection: A golden two hours for detection.
AB  - Undetected error in safety critical contexts generates a latent condition that
      can contribute to a future safety failure. The detection of latent errors post
      task completion is observed in naval air engineers using a diary to record work
      related latent error detection (LED) events. A systems view is combined with
      multi-process theories to explore sociotechnical factors associated with LED.
      Perception of cues in different environments facilitates successful LED, for
      which the deliberate review of past tasks within two hours of the error occurring
      and whilst remaining in the same or similar sociotechnical environment to that
      which the error occurred appears most effective. Identified ergonomic
      interventions offer potential mitigation for latent errors; particularly in
      simple everyday habitual tasks. It is thought safety critical organisations
      should look to engineer further resilience through the application of LED
      techniques that engage with system cues across the entire sociotechnical
      environment, rather than relying on consistent human performance.

PMID- 27890118
TI  - 3D digital headform models of Australian cyclists.
AB  - Traditional 1D anthropometric data have been the primary source of information
      used by ergonomists for the dimensioning of head and facial gear. Although these
      data are simple to use and understand, they only provide univariate measures of
      key dimensions. 3D anthropometric data, however, describe the complete shape
      characteristics of the head surface, but are complicated to interpret due to the
      abundance of information they contain. Consequently, current headform standards
      based on 1D measurements may not adequately represent the actual head shape
      variations of the intended user groups. The purpose of this study was to
      introduce a set of new digital headform models representative of the adult
      cyclists' community in Australia. Four models were generated based on an
      Australian 3D anthropometric database of head shapes and a modified hierarchical
      clustering algorithm. Considerable shape differences were identified between our
      models and the current headforms from the Australian standard. We conclude that
      the design of head and facial gear based on current standards might not be
      favorable for optimal fitting results.

PMID- 27890119
TI  - How do health service professionals consider human factors when purchasing
      interactive medical devices? A qualitative interview study.
AB  - We present findings of a UK study into how those involved in purchasing
      interactive medical devices go about evaluating usability, the challenges that
      arise, and opportunities for improvement. The study focused on procurement of
      infusion devices because these are used by various professionals across
      healthcare. A semi-structured interview study was carried out involving a range
      of stakeholders (20 in total) involved in or impacted by medical device
      procurement. Data was analysed using thematic analysis, a qualitative method
      designed to support the identification, analysis and reporting of patterns. In
      principle, health service purchasing was found to accommodate consideration of
      equipment usability. In practice, the evaluation process was driven primarily by
      engineering standards; assessment of local needs did not accommodate substantive
      assessment of usability; and choice was limited by the availability of equipment
      on the marketplace. We discuss ways in which purchasing could be improved through
      techniques that account for social circumstances.

PMID- 27890120
TI  - Influence of lane departure warnings onset and reliability on car drivers'
      behaviors.
AB  - Lane departures represent an important cause of road crashes. The objective of
      the present study was to assess the effects of an auditory Lane Departure Warning
      System (LDWS) for partial and full lane departures (onset manipulation) combined
      with missed warnings (reliability manipulation: 100% reliable, 83% reliable and
      66% reliable) on drivers' performances and acceptance. Several studies indicate
      that LDWS improves drivers' performances during lane departure episodes. However,
      little is known about the effects of the warning onset and reliability of LDWS.
      Results of studies which looked at forward collision warning systems show that
      early warnings tend to improve drivers' performances and receive a better trust
      judgement from the drivers when compared to later warnings. These studies also
      suggest that reliable assistances are more effective and trusted than unreliable
      ones. In the present study, lane departures were brought about by means of a
      distraction task whilst drivers simulated driving in a fixed-base simulator with
      or without an auditory LDWS. Results revealed steering behaviors improvements
      with LDWS. More effective recovery maneuvers were found with partial lane
      departure warnings than with full lane departure warnings and assistance
      unreliability did not impair significantly drivers' behaviors. Regarding missed
      lane departure episodes, drivers were found to react later and spend more time
      out of the driving lane when compared to properly warned lane departures, as if
      driving without assistance. Subjectively, LDWS did not reduce mental workload and
      partial lane departure warnings were judged more trustworthy than full lane
      departure ones. Data suggests the use of partial lane departure warnings when
      designing LDWS and that even unreliable LDWS may draw benefits compared to no
      assistance.

PMID- 27890121
TI  - Prevalence and risk factors associated with musculoskeletal complaints among
      users of mobile handheld devices: A systematic review.
AB  - This systematic review aimed at evaluating the prevalence and risk factors for
      musculoskeletal complaints associated with mobile handheld device use. Pubmed,
      Medline, Web of Science, CINAHL and Embase were searched. The methodological
      quality of included studies was assessed. Strength of evidence for risk factors
      was determined based on study designs, methodological quality and consistency of
      results. Five high-quality, eight acceptable-quality and two low-quality peer
      reviewed articles were included. This review demonstrates that the prevalence of
      musculoskeletal complaints among mobile device users ranges from 1.0% to 67.8%
      and neck complaints have the highest prevalence rates ranging from 17.3% to
      67.8%. This study also finds some evidence for neck flexion, frequency of phone
      calls, texting and gaming in relation to musculoskeletal complaints among mobile
      device users. Inconclusive evidence is shown for other risk factors such as
      duration of use and human-device interaction techniques due to inconsistent
      results or a limited number of studies.

PMID- 27890122
TI  - Safety in passenger ships: The influence of environmental design characteristics
      on people's perception of safety.
AB  - Although objective safety is a widely studied topic in ergonomics, subjective
      safety has received far less research attention. Nevertheless, most of human
      decision-making and behavior depends on how we perceive our environment. This
      study investigates the effects of various environmental design characteristics on
      people's safety perception in a passenger ship context. Five different
      environmental design characteristics were manipulated to increase the openness of
      the space or to create more clear navigation, resulting in 20 different cabin
      corridors for a passenger ship. Ninety-seven respondents were asked to rate these
      corridors on the perceived safety in an experiment. The results showed that
      people feel more safe when the corridors have a curved ceiling, when the walls do
      not have a split-level design, and when there is a view to the outside. Designers
      can use these insights when designing future environments.

PMID- 27890123
TI  - Psychophysical evaluation of auditory signals in passenger vehicles.
AB  - Twenty-one experienced drivers were recruited for the evaluation of sounds of
      four functions (horn, indicator, door open warning, and parking sensor) made by
      11 car brand names. Each participant was required to evaluate all of the above
      sound signals by a pair-comparison test. After the comparison test, each
      participant was shown his/her pair-comparison result and was asked to comment on
      their preference and appropriateness of a sound. The physical properties and
      interview data were compared and summarized to propose design recommendations.
      Our results indicate that complex tones and a fundamental frequency around 450 Hz
      were most preferred for horns while for indicators the preferred sounds had a
      higher dominant frequency [corrected].To reduce monotony, the indicators with
      double clicks and an OFF time interval of between 330 and 400 ms between two
      clicks were most preferred. Regarding door warning sounds, the waveform starting
      with a higher intensity then fading towards zero intensity is most preferred
      while for parking sensors, sounds beginning with a longer OFF time (about 500 ms)
      and having 3 or 4 distinctive tempo variations were most preferred. The
      relationship between pleasurability and pitch, loudness, and the tempo of sound
      signals basically followed an inverted-U function. Sound designers should avoid
      using very extreme parameter values when generating sound for a given function.

PMID- 27890124
TI  - Clothing-related barriers experienced by people with mobility disabilities and
      impairments.
AB  - Clothing-related issues can create barriers to social participation and other
      desired activities for people living with disabilities and their families. The
      purpose of this study was to identify clothing-related barriers people living
      with disabilities and their families are facing. An online survey was
      administered to people living with disabilities and parents/caregivers, resulting
      in a sample of 113 participants indicating mobility impairments. Survey results
      indicated that the clothing needs of people living with disabilities and
      impairments are not being met, the lack of appropriate clothing prevented
      individuals from fully engaging in social activities and relationships,
      employment or everyday life events. The design fields and apparel industry could
      play a vital role in helping people with mobility disabilities navigate these
      barriers.

PMID- 27890125
TI  - Human-centered design (HCD) of a fault-finding application for mobile devices and
      its impact on the reduction of time in fault diagnosis in the manufacturing
      industry.
AB  - The present article describes the design process of a fault-finding application
      for mobile devices, which was built to support workers' performance by guiding
      them through a systematic strategy to stay focused during a fault-finding
      process. In collaboration with a project partner in the manufacturing industry, a
      fault diagnosis application was conceptualized based on a human-centered design
      approach (ISO 9241-210:2010). A field study with 42 maintenance workers was
      conducted for the purpose of evaluating the performance enhancement of fault
      finding in three different scenarios as well as for assessing the workers'
      acceptance of the technology. Workers using the mobile device application were
      twice as fast at fault finding as the control group without the application and
      perceived the application as very useful. The results indicate a vast potential
      of the mobile application for fault diagnosis in contemporary manufacturing
      systems.

PMID- 27890126
TI  - HTO - A complementary ergonomics approach.
AB  - The field of human factors and ergonomics constitutes a strong potential in
      systems analysis, design and improvement. However, it is difficult to communicate
      its potential value. This paper addresses how the human-technology-organization
      (HTO) concept can be defined and supports the understanding, communication and
      development of the systems' character and potential of human factors and
      ergonomics. Empirical examples from the authors' experiences of working with the
      HTO concept in R&D and teaching are illustrated, including its usefulness as: 1)
      a conceptual model; 2) an analysis framework; 3) a meta methodology; 4) a
      pedagogical tool; and 5) a design tool. The use of HTO provides guidance on how
      the system can be designed to better support health, individual and systems
      performance. It is further suggested that there is a strong potential for
      developing the theory, applications and methodological aspects of HTO.

PMID- 27890127
TI  - Evaluating a digital ship design tool prototype: Designers' perceptions of novel
      ergonomics software.
AB  - Computer-aided solutions are essential for naval architects to manage and
      optimize technical complexities when developing a ship's design. Although there
      are an array of software solutions aimed to optimize the human element in design,
      practical ergonomics methodologies and technological solutions have struggled to
      gain widespread application in ship design processes. This paper explores how a
      new ergonomics technology is perceived by naval architecture students using a
      mixed-methods framework. Thirteen Naval Architecture and Ocean Engineering
      Masters students participated in the study. Overall, results found participants
      perceived the software and its embedded ergonomics tools to benefit their design
      work, increasing their empathy and ability to understand the work environment and
      work demands end-users face. However, participant's questioned if ergonomics
      could be practically and efficiently implemented under real-world project
      constraints. This revealed underlying social biases and a fundamental lack of
      understanding in engineering postgraduate students regarding applied ergonomics
      in naval architecture.

PMID- 27890128
TI  - Johnny was here: From airmanship to airlineship.
AB  - In this article we explore the phenomenon of airmanship in commercial passenger
      flights, in a context of increasing standardisation of procedures and
      technologies. Through observation studies in cockpits and interviews we have
      studied pilots' practices and how they relate to the larger system of procedures
      and the technical environment. We find that practices are to a large extent
      guided by standard operating procedures, and that interchangeability of pilots
      and aircrafts is both a prerequisite for and enabled by this standardised regime.
      However, since sociotechnical systems in general - and operation of aircrafts is
      no exception - are inherently underspecified, the pilots' exercise of discretion
      in their context-sensitive adaptation of the procedures and technical
      environments is another prerequisite for well-functioning systems. Mastering
      these adaptations - and recognising the absolute delimitations of adaptations -
      is a central aspect of airmanship. Outside this space of manoeuvre for the
      pilots, the aircrafts are managed by what we call airlineship: The inter
      organisational efforts to create predictability and safe practices through de
      identification and interchangeability of personnel and aircrafts. Pilots are
      actors in sociotechnical systems that are not demarcated by the cockpits. To
      understand pilots' work, studies must account also for the wider sociotechnical
      context of organisational, regulative and techno-material structures. The article
      is a contribution to the a generic attempt in the field of ergonomics to
      contribute with models and theories that portray individuals, groups,
      organisations and systems in ways that keep sight of the individuals in the
      systems and the systems in the individuals at the same time.

PMID- 27890129
TI  - Toe spatiotemporal differences between transition steps when ascending shorter
      flight stairways of different heights.
AB  - BACKGROUND: Studies have typically treated the first and second floor-to-stair
      transition steps (TS1 and TS2) as one stride. However, because the foot is devoid
      of plantar cutaneous input from the stair surface at TS1, these steps may have
      different toe spatiotemporal profiles, and resultantly, different
      susceptibilities to a trip and/or a fall. This study compared vertical toe
      clearance, forward velocity, and their respective variability magnitudes between
      TS1 and TS2 when ascending stairs of different heights. METHODS: Twenty young
      adults (seven males and 13 females) (21.68 +/- 2.49 years; 169.70 +/- 9.56 cm;
      63.91 +/- 9.62 kg) negotiated an intervening three-step staircase placed midpoint
      on a 10 m walkway. There were three stair heights: low stairs (LS), medium stairs
      (MS), and high stairs (HS). Vertical toe clearance, forward velocity, and their
      variability magnitudes were calculated. RESULTS: Vertical toe clearance was only
      higher (P < 0.05) at TS1 than TS2 in the medium and high stairs. Vertical toe
      clearance was more variable (P < 0.05) in the low compared to medium stairs.
      Also, forward toe velocity was greater at TS1 than TS2, but was lower in the
      medium and high stairs. CONCLUSION: The locomotor system appeared cautious by
      exaggerating vertical toe clearance at both TS1 and TS2 only in low stairs,
      possibly due to higher forward toe velocity. If the exaggeration strategy
      consistently persists, this finding may suggest decreased trip or fall risk at
      both TS1 and TS2 only when transitioning onto low stairs.

PMID- 27890130
TI  - Hot under the collar: The impact of heat on game play.
AB  - High temperatures have been documented to affect behavior in a variety of ways
      depending on the nature of the task. We extended this prior research by examining
      the effects of dynamically changing temperature on various aspects of performance
      in a video game task. In the span of approximately an hour, temperature was
      gradually increased, stayed constant for a period of time, and gradually
      decreased to baseline. The gaming task was a variation on one used to assess
      impulsivity in participants thus allowing the possibility of assessing the
      effects of temperature on impulsive choice. Rather than heat increasing
      impulsivity and thus decreasing wait times, participants showed increases in wait
      times as temperature increased which either suggests that participants were
      becoming more self-controlled under heat or that the documented negative impact
      of heat on motor functioning was dominating their performance. Importantly, the
      participant's sensitivity to the changing task requirements was not affected by
      changes in temperature.

PMID- 27890131
TI  - The role of size of input box, location of input box, input method and display
      size in Chinese handwriting performance and preference on mobile devices.
AB  - This study presented two experiments on Chinese handwriting performance (time,
      accuracy, the number of protruding strokes and number of rewritings) and
      subjective ratings (mental workload, satisfaction, and preference) on mobile
      devices. Experiment 1 evaluated the effects of size of the input box, input
      method and display size on Chinese handwriting performance and preference. It was
      indicated that the optimal input sizes were 30.8 * 30.8 mm, 46.6 * 46.6 mm, 58.9
      * 58.9 mm and 84.6 * 84.6 mm for devices with 3.5-inch, 5.5-inch, 7.0-inch and
      9.7-inch display sizes, respectively. Experiment 2 proved the significant effects
      of location of the input box, input method and display size on Chinese
      handwriting performance and subjective ratings. It was suggested that the optimal
      location was central regardless of display size and input method.

PMID- 27890132
TI  - The stage of change approach for implementing ergonomics advice - Translating
      research into practice.
AB  - The Stage of Change (SOC) approach has been proposed as a method to improve the
      implementation of ergonomics advice. However, despite evidence for its efficacy
      there is little evidence to suggest it has been adopted by ergonomics
      consultants. This paper investigates barriers and facilitators to the
      implementation, monitoring and effectiveness of ergonomics advice and the
      adoption of the SOC approach in a series of focus groups and a subsequent survey
      of members of the Human Factors Societies of Australia and New Zealand. A
      proposed SOC assessment tool developed for use by ergonomics practitioners is
      presented. Findings from this study suggest the limited application of a SOC
      based approach to work-related musculoskeletal injury prevention by ergonomics
      practitioners is due to the absence of a suitable tool in the ergonomists'
      repertoire, the need for training in this approach, and their limited access to
      relevant research findings. The final translation of the SOC assessment tool into
      professional ergonomics practice will require accessible demonstration of its
      real-world usability to practitioners and the training of ergonomics
      practitioners in its application.

PMID- 27890133
TI  - Blood sampling - Two sides to the story.
AB  - This study aimed to investigate why there is variability in taking blood. A multi
      method Pilot study was completed in four National Health Service Scotland
      hospitals. Human Factors/Ergonomics principles were applied to analyse data from
      50 observations, 15 interviews and 12-months of incident data from all Scottish
      hospitals. The Functional Resonance Analysis Method (FRAM) was used to understand
      why variability may influence blood sampling functions. The analysis of the 61
      pre blood transfusion sampling incidents highlighted limitations in the data
      collected to understand factors influencing performance. FRAM highlighted how
      variability in the sequence of blood sampling functions and the number of
      practitioners involved in a single blood sampling activity was influenced by the
      working environment, equipment, clinical context, work demands and staff
      resources. This pilot study proposes a realistic view of why blood sampling
      activities vary and proposes the need to consider the system's resilience in
      future safety management strategies.

PMID- 27890134
TI  - The relationship between arch height and foot length: Implications for size
      grading.
AB  - OBJECTIVE: Medial longitudinal Arch Height is synonymous with classifying foot
      type and conversely foot function. Detailed knowledge of foot anthropometry is
      essential in the development of ergonomically sound footwear. Current Footwear
      design incorporates a direct proportionate scaling of instep dimensions with
      those of foot length. The objective of this paper is to investigate if a direct
      proportional relationship exists between human arch height parameters and foot
      length in subjects with normal foot posture. METHOD: A healthy convenience sample
      of 62 volunteers was recruited to participate in this observational study. All
      subjects were screened for normal foot health and posture. Each subject's foot
      dimensions were scanned and measured using a 3D Foot Scanner. From this foot
      length and arch height parameters were obtained. Normalised ratios of arch height
      with respect to foot length were also calculated. The arch height parameters and
      the normalised arch ratios were used interchangeably as the dependent variables
      with the foot length parameters used as the independent variable for Simple
      Linear Regression and Correlation. RESULTS: Analysis of foot length measures
      demonstrated poor correlation with all arch height parameters. CONCLUSION: No
      significant relationships between arch height and foot length were found. The
      predictive value of the relationship was found to be poor. This holds significant
      implications for the current method of proportionate scaling of footwear in terms
      of fit and function to the midfoot region for a normative population.

PMID- 27890135
TI  - Human factors in the design of medical devices - Approaches to meeting
      international standards in the European Union and USA.
AB  - This paper focuses on the challenges of meeting agency requirements as it
      pertains to the application of human factors in the medical device development
      (MDD) process. Individual case studies of the design and development process for
      18 medical device manufacturers located in the US and EU were analyzed and
      compared using a multiple case study design. The results indicate that there are
      four main challenges in implementing international standards. These include a
      lack of direct access to users for the purposes of device development; a lack of
      understanding by users with regards to the impact of their feedback on the
      development process; contract formalities limiting user exchanges; and the
      attitude of clinical users directly impacting on the device developer's
      invitation to participate in the development processes. The barriers presented in
      this research have the potential to be resolved but only with greater commitment
      by both medical device users and developers.

PMID- 27890136
TI  - Age-related differences in decision-making for digital escape route signage under
      strenuous emergency conditions of tilted passenger ships.
AB  - This age-differentiated study investigated preferences for new digital, situation
      adaptive escape route signage with informative and flashing elements under
      simulated emergency conditions of tilted passenger ships. The decision-making
      behaviour of 26 young (20-30 years) and 26 elderly (60-77 years) participants was
      observed in four conditions varying in applied stressors and in level versus
      uphill walking at 7 degrees  and 14 degrees . In line with previous studies,
      decisions of young participants were significantly influenced by flashing
      elements on signs. In contrast, elderly participants based their decisions
      significantly stronger on integrated information about the sign's updatedness and
      reported irritation by flashing elements. These preferences were also persistent
      under increased mental, emotional and physical strain, evaluated by ratings and
      (psycho-)physiological measures. The findings demonstrate the importance to
      carefully design digital, situation-adaptive signage for passenger ships in a way
      that it not only attracts attention but also inspires trust especially for the
      elderly population.

PMID- 27890137
TI  - The identification of combat survivability tasks associated with naval vessel
      damage in maritime environments.
AB  - Effective Navy personnel have the physical ability to perform combat
      survivability tasks commensurate with their unique physical requirements due to
      the distinctive characteristics of naval platforms. The aim of this investigation
      was to identify the physically demanding whole-of-ship tasks that are performed
      by Navy personnel while at sea. A mixed method design was used to identify tasks,
      inclusive of focus groups and field observations. From a series of ten focus
      groups, nine tasks were deemed to be physically demanding whole-of-ship tasks. A
      subsequent field observation of a combat survivability training course resulted
      in a refined and expanded 33-item list of physically demanding whole-of-ship
      tasks across six categories, including; replenishment at sea, emergency response,
      firefighting, leak stop and repair, toxic hazard and casualty evacuation. The
      findings from this study provide the basis for the development of physical
      employment standards for whole-of-ship tasks within the Royal Australian Navy.

PMID- 27890138
TI  - Individual differences in cardiorespiratory measures of mental workload: An
      investigation of negative affectivity and cognitive avoidant coping in pilot
      candidates.
AB  - Cardiorespiratory measures provide useful information in addition to well
      established self-report measures when monitoring operator capacity. The purpose
      of our study was to refine the assessment of operator load by considering
      individual differences in personality and their associations with
      cardiorespiratory activation. Physiological and self-report measures were
      analyzed in 115 pilot candidates at rest and while performing a multiple task
      covering perceptual speed, spatial orientation, and working memory. In the total
      sample and particularly in individuals with a general tendency to worry a lot, a
      cognitive avoidant coping style was associated with a smaller task-related
      increase in heart rate. Negative affectivity was found to moderate the
      association between cardiac and self-reported arousal. Given that physiological
      and self-report measures of mental workload are usually combined when evaluating
      operator load (e.g., in pilot selection and training), our findings suggest that
      integrating individual differences may reduce unexplained variance and increase
      the validity of workload assessments.

PMID- 27890139
TI  - Toward a taxonomy of the unintentional discharge of firearms in law enforcement.
AB  - An unintentional discharge (UD) is an activation of the trigger mechanism that
      results in an unplanned discharge that is outside of the firearm's prescribed
      use. UDs can result in injury or death, yet have been understudied in scientific
      literature. Pre-existing (1974-2015) UD reports (N = 137) from seven law
      enforcement agencies in the United States of America were analyzed by context,
      officer behavior, type of firearm, and injuries. Over 50% of UDs occurred in
      contexts with low threat potential while engaged in routine firearm tasks. The
      remaining UDs occurred in contexts with elevated to high threat potential during
      muscle co-activation, unfamiliar firearm tasks, contact with inanimate objects,
      and a medical condition. An antecedent-behavior-consequence (A-B-C) taxonomy as
      well as a standardized reporting form, based on the current findings and the
      existing literature, are offered as tools for identifying the conditions under
      which UDs may be likely to occur.

PMID- 27890140
TI  - Evaluation of the vibration attenuation properties of an air-inflated cushion
      with two different heavy machinery seats in multi-axis vibration environments
      including jolts.
AB  - Seats and cushions can attenuate whole-body vibration (WBV) exposures and
      minimize health risks for heavy machine operators. We successfully developed
      neural network (NN) algorithms to identify the vibration attenuation properties
      for four different seating conditions (seat/cushion combinations), and
      implemented each of the NN models to predict the equivalent daily exposure A(8)
      values for various vehicles in the forestry and mining environments. We also
      evaluated the performance of the new prototype No-JoltTM air-inflated cushion and
      the original cushion of each seat with jolt exposures. We observed that the air
      cushion significantly improved the vibration attenuation properties of the seat
      that initially had good performance, but not for the seat that had relatively
      poor vibration attenuation properties. In addition, operator's anthropometrics
      and sex influenced the performance of the air-inflated cushion when the vibration
      environment included jolt exposures.

PMID- 27890141
TI  - How to assess driver's interaction with partially automated driving systems - A
      framework for early concept assessment.
AB  - The introduction of partially automated driving systems changes the driving task
      into supervising the automation with an occasional need to intervene. To develop
      interface solutions that adequately support drivers in this new role, this study
      proposes and evaluates an assessment framework that allows designers to evaluate
      driver-support within relevant real-world scenarios. Aspects identified as
      requiring assessment in terms of driver-support within the proposed framework are
      Accident Avoidance, gained Situation Awareness (SA) and Concept Acceptance.
      Measurement techniques selected to operationalise these aspects and the
      associated framework are pilot-tested with twenty-four participants in a driving
      simulator experiment. The objective of the test is to determine the reliability
      of the applied measurements for the assessment of the framework and whether the
      proposed framework is effective in predicting the level of support offered by the
      concepts. Based on the congruency between measurement scores produced in the test
      and scores with predefined differences in concept-support, this study
      demonstrates the framework's reliability. A remaining concern is the framework's
      weak sensitivity to small differences in offered support. The article concludes
      that applying the framework is especially advantageous for evaluating early
      design phases and can successfully contribute to the efficient development of
      driver's in-control and safe means of operating partially automated vehicles.

PMID- 27890142
TI  - The effects of a simple intervention on exposures to low back pain risk factors
      during traditional posterior load carriage.
AB  - Traditional posterior load carriage (PLC), typically performed without the use of
      an assistive device, is associated with a high prevalence of low back pain (LBP).
      However, there are few studies that have evaluated potential interventions to
      reduce exposures to LBP risk factors. This work examined the effects of a simple,
      potentially low-cost intervention using an assistive device (i.e., carrying aid)
      on exposures to factors related to LBP risk during PLC. Torso kinematics and
      kinetics, slip risk, and ratings of perceived discomfort (RPD) were obtained
      during simulated PLC on a walkway. Consistent with earlier results, increasing
      load mass substantially increased torso flexion and lumbosacral flexion moment,
      as well as RPDs in all anatomical regions evaluated. Using the carrying aid with
      a higher load placement resulted in substantially lower mean lumbosacral moments
      when carrying the heaviest load. In contrast, using the carrying aid with a lower
      load placement resulted in substantially higher torso flexion angles, higher mean
      lumbosacral moments when carrying heavier loads, and higher peak lumbosacral
      moments across all load masses. With use of the carrying aid, both higher and
      lower load placement resulted in significantly lower RPDs in the elbows and hands
      compared to the control condition. In summary, use of a carrying aid with higher
      load placement may be beneficial in reducing the risk of LBP during PLC. Future
      studies are needed, though, to improve the device design and to enhance external
      validity.

PMID- 27890143
TI  - What work schedule characteristics constitute a problem to the individual? A
      representative study of Swedish shift workers.
AB  - The purpose was to investigate which detailed characteristics of shift schedules
      that are seen as problems to those exposed. A representative national sample of
      non-day workers (N = 2031) in Sweden was asked whether they had each of a number
      of particular work schedule characteristics and, if yes, to what extent this
      constituted a "big problem in life". It was also inquired whether the
      individual's work schedules had negative consequences for fatigue, sleep and
      social life. The characteristic with the highest percentage reporting a big
      problem was "short notice (<1 month) of a new work schedule" (30.5%), <11 h off
      between shifts (27.8%), and split duty (>1.5 h break at mid-shift, 27.2%).
      Overtime (>10 h/week), night work, morning work, day/night shifts showed lower
      prevalences of being a "big problem". Women indicated more problems in general.
      Short notice was mainly related to negative social effects, while <11 h off
      between shifts was related to disturbed sleep, fatigue and social difficulties.
      It was concluded that schedules involving unpredictable working hours (short
      notice), short daily rest between shifts, and split duty shifts constitute big
      problems. The results challenge current views of what aspects of shift work need
      improvement, and negative social consequences seem more important than those
      related to health.

PMID- 27890144
TI  - Classification of a Driver's cognitive workload levels using artificial neural
      network on ECG signals.
AB  - An artificial neural network (ANN) model was developed in the present study to
      classify the level of a driver's cognitive workload based on electrocardiography
      (ECG). ECG signals were measured on 15 male participants while they performed a
      simulated driving task as a primary task with/without an N-back task as a
      secondary task. Three time-domain ECG measures (mean inter-beat interval (IBI),
      standard deviation of IBIs, and root mean squared difference of adjacent IBIs)
      and three frequencydomain ECG measures (power in low frequency, power in high
      frequency, and ratio of power in low and high frequencies) were calculated. To
      compensate for individual differences in heart response during the driving tasks,
      a three-step data processing procedure was performed to ECG signals of each
      participant: (1) selection of two most sensitive ECG measures, (2) definition of
      three (low, medium, and high) cognitive workload levels, and (3) normalization of
      the selected ECG measures. An ANN model was constructed using a feed-forward
      network and scaled conjugate gradient as a back-propagation learning rule. The
      accuracy of the ANN classification model was found satisfactory for learning data
      (95%) and testing data (82%).

PMID- 27890145
TI  - Gait adaptation on surfaces with different degrees of slipperiness.
AB  - Gait adaptation to employ different ways to avoid a potential slip is needed to
      continue walking safely on a new surface, especially when transitioning to a
      slippery surface. In this experiment, participants walked back and forth five
      times (trials) on surfaces with different degrees of slipperiness. The results
      show that trial 1 was significantly different from other trials for most of the
      dependent variables, especially for the low and high friction conditions.
      Kinematics on high and medium friction surfaces were very similar, but more
      adjustments were needed for low friction surfaces. The data for the first trial
      reflect gait after walking for 2.4 m on the walkway, not the first step onto the
      walkway. The current data show that gait adaptation continued beyond the first
      trial. Since participants in this experiment were aware of the floor conditions,
      the results could have important safety implications that user awareness alone
      might be insufficient for safe floor designs.

PMID- 27890146
TI  - Measuring wildland fire fighter performance with wearable technology.
AB  - Wildland (rural) fire fighting is a physically demanding and hazardous
      occupation. An observational study was conducted to explore the use of new
      technologies for the field study of fire fighters at wildfires and to understand
      the work pressures of wildland fire fighting. The research was carried out with
      two fire fighters at real fires wearing microphones, miniature video cameras,
      heart rate monitors and GPS units to record their actions and location at
      wildfire events. The fire fighters were exposed to high physiological workloads
      (heart rates of up to 180 beats per minute) and walked considerable distances at
      the fires. Results from this study have been used in presentations to fire
      fighters and non-operational fire personnel to understand the pressures fire
      fighters are under and how others complete the fire fighting tasks.

PMID- 27890147
TI  - Using a bespoke situated digital kiosk to encourage user participation in
      healthcare environment design.
AB  - Involving users through participation in healthcare service and environment
      design is growing. Existing approaches and toolkits for practitioners and
      researchers are often paper based involving workshops and other more traditional
      design approaches such as paper prototyping. The advent of digital technology
      provides the opportunity to explore new platforms for user participation. This
      paper presents results from three studies that used a bespoke situated user
      participation digital kiosk, engaging 33 users in investigating healthcare
      environment design. The studies, from primary and secondary care settings,
      allowed participant feedback on each environment and proved a novel, engaging
      "21st century" way to participate in the appraisal of the design process. The
      results point toward this as an exciting and growing area of research in
      developing not just a new method of user participation but also the technology
      that supports it. Limitations were noted in terms of data validity and engagement
      with the device. To guide the development of user participation using similar
      situated digital devices, key lessons and reflections are presented.

PMID- 27890148
TI  - Seated reach capabilities for ergonomic design and evaluation with consideration
      of reach difficulties.
AB  - This paper aimed to identify the reach capabilities of 26 seated subjects
      considering the reach difficulty, orientation and other potential factors, and to
      find a method to model the minimum reach capability surfaces for fixed and
      adjustable seats. The reach capability radius was used as a measure of the reach
      capability and theoretically modeled. Based on the test data of seated reach, the
      distribution of the reach capability radius was analyzed. The strategy to select
      the minimum reach envelopes was constructed to accommodate a sufficient
      percentage of the target population for both fixed and adjustable seats. For
      adjustable seats, a method was developed to derive the reach capability data from
      the tested individual reach capability data by introducing seating position
      models to re-position the individual reach capability data. An application case
      was realized based on the cab packaging data of a mini-van, and the minimum reach
      envelopes of different difficulties were created and validated to accommodate 90%
      of the target population.

PMID- 27890149
TI  - Assessing the effectiveness of five process elicitation methods: A case study of
      chemotherapy treatment plan review.
AB  - To reduce the probability of failures and to improve outcomes of safety-critical
      human-intensive processes, such as health care processes, it is important to be
      able to rigorously analyze such processes. The quality of that analysis often
      depends on having an accurate, detailed, and sufficiently complete understanding
      of the process being analyzed, where this understanding is typically represented
      as a formal process model that could then drive various rigorous analysis
      approaches. Developing this understanding and the corresponding formal process
      model may be difficult and, thus, a variety of process elicitation methods are
      often used. The work presented in this paper evaluates the effectiveness of five
      common elicitation methods in terms of their ability to elicit detailed process
      information necessary to support rigorous process analysis. These methods are
      employed to elicit typical steps and steps for responding to exceptional
      situations in a safety-critical health care process, the chemotherapy treatment
      plan review process. The results indicate strengths and weaknesses of each of the
      elicitation methods and suggest that it is preferable to apply multiple
      elicitation methods.

PMID- 27890150
TI  - Assessing ergonomic risks of software: Development of the SEAT.
AB  - Software utilizing interaction designs that require extensive dragging or
      clicking of icons may increase users' risks for upper extremity cumulative trauma
      disorders. The purpose of this research is to develop a Self-report Ergonomic
      Assessment Tool (SEAT) for assessing the risks of software interaction designs
      and facilitate mitigation of those risks. A 28-item self-report measure was
      developed by combining and modifying items from existing industrial ergonomic
      tools. Data were collected from 166 participants after they completed four
      different tasks that varied by method of input (touch or keyboard and mouse) and
      type of task (selecting or typing). Principal component analysis found distinct
      factors associated with stress (i.e., demands) and strain (i.e., response).
      Repeated measures analyses of variance showed that participants could
      discriminate the different strain induced by the input methods and tasks.
      However, participants' ability to discriminate between the stressors associated
      with that strain was mixed. Further validation of the SEAT is necessary but these
      results indicate that the SEAT may be a viable method of assessing ergonomics
      risks presented by software design.

PMID- 27890151
TI  - A simplified thermoregulation model of the human body in warm conditions.
AB  - Thermoregulation models of the human body have been widely used in thermal
      comfort studies. The existing models are complicated and not fully verified for
      application in China. This paper presents a simplified thermoregulation model
      which has been statistically validated by the predicted and measured mean skin
      temperature in warm environments, including 21 typical conditions with 400
      Chinese subjects. This model comprises three parts: i) the physical model; ii)
      the controlled system; and iii) the controlling system, and considers three key
      questions formerly ignored by the existing models including: a) the evaporation
      efficiency of regulatory sweat; b) the proportional relation of total skin blood
      flow and total heat loss by regulatory sweating against body surface area; and c)
      discrepancies in the mean skin temperatures by gender. The developed model has
      been validated to be within the 95% confidence interval of the population mean
      skin temperature in three cases.

PMID- 27890152
TI  - Analysis of human motion variation patterns using UMPCA.
AB  - The rapid development of motion capture technologies has greatly increased the
      use of human motion data in many applications. This has increased the demand to
      have an effective means to systematically analyze those massive data in order to
      understand human motion variation patterns. This paper studies one typical type
      of motion data, which are recorded as multi-stream trajectories of human joints.
      Such a high dimensional multi-stream data structure makes it difficult to
      directly perform visual comparisons or simply apply conventional methods such as
      PCA to capture the variation of human motion patterns. In this paper, a high
      order array (tensor) is suggested for data representation, based on which the
      Uncorrelated Multilinear Principal Component Analysis (UMPCA) is applied to
      analyze the variation of human motion patterns. A simulation study is presented
      to show the superiority of UMPCA over PCA in preserving the cross-correlation
      among multi-stream trajectories. The effectiveness of UMPCA is also demonstrated
      using a case study for analyzing vehicle ingress test data.

PMID- 27890153
TI  - The 'Arm Force Field' method to predict manual arm strength based on only hand
      location and force direction.
AB  - This paper describes the development of a novel method (termed the 'Arm Force
      Field' or 'AFF') to predict manual arm strength (MAS) for a wide range of body
      orientations, hand locations and any force direction. This method used an
      artificial neural network (ANN) to predict the effects of hand location and force
      direction on MAS, and included a method to estimate the contribution of the arm's
      weight to the predicted strength. The AFF method predicted the MAS values very
      well (r2 = 0.97, RMSD = 5.2 N, n = 456) and maintained good generalizability with
      external test data (r2 = 0.842, RMSD = 13.1 N, n = 80). The AFF can be readily
      integrated within any DHM ergonomics software, and appears to be a more robust,
      reliable and valid method of estimating the strength capabilities of the arm,
      when compared to current approaches.

PMID- 27890154
TI  - Effects of tool handle dimension and workpiece orientation and size on wrist
      ulnar/radial torque strength, usability and discomfort in a wrench task.
AB  - The effects of tool handle dimension (three modified designs of wrenches with 30
      50 mm diameter cylindrical handles and traditional design with rectangular cross
      sectional (5 mm * 25 mm) handle), workpiece orientation (vertical/horizontal) and
      workpiece size (small/large) as well as user's hand size on wrist ulnar/radial
      (U/R) torque strength, usability and discomfort, and also the relationship
      between these variables were evaluated in a maximum torque task using wrenches.
      The highest and lowest levels of maximal wrist U/R torque strength were recorded
      for the 30 mm diameter handle and traditional wrench design, respectively. The
      prototype handle with 30 mm diameter, together with 40 mm diameter handle, was
      also better than other designs as they received higher usability ratings and
      caused less discomfort. The mean wrist torque strength exerted on a vertically
      oriented workpiece (in the sagittal plane) was 23.8% higher than that exerted on
      a horizontally oriented one (in the transverse plane). The user's hand size had
      no effect on torque exertions. The wrist torque strength and usability were
      negatively correlated with hand and finger discomfort ratings. The results are
      also discussed in terms of their implications for hand tool and workstation
      configuration in torque tasks involving wrenches.

PMID- 27890155
TI  - Factors influencing experience in crowds - The participant perspective.
AB  - Humans encounter crowd situations on a daily basis, resulting in both negative
      and positive experiences. Understanding how to optimise the participant
      experience of crowds is important. In the study presented in this paper, 5 focus
      groups were conducted (35 participants, age range: 21-71 years) and 55 crowd
      situations observed (e.g. transport hubs, sport events, retail situations).
      Influences on participant experience in crowds identified by the focus groups and
      observations included: physical design of crowd space and facilities (layout,
      queuing strategies), crowd movement (monitoring capacity, pedestrian flow),
      communication and information (signage, wayfinding), comfort and welfare
      (provision of facilities, environmental comfort), and public order. It was found
      that important aspects affecting participant experience are often not considered
      systematically in the planning of events or crowd situations. The findings point
      to human factors aspects of crowds being overlooked, with the experiences of
      participants often poor.

PMID- 27890156
TI  - Physiological and perceptual effects of a cooling garment during simulated
      industrial work in the heat.
AB  - OBJECTIVE: Evaluate physiological and perceptual responses using a phase change
      cooling (PCC) garment during simulated work in the heat. METHODS: Twenty males
      wearing compression undergarments, coverall suit, gloves, and hard-hat, completed
      two randomly assigned trials (with PCC inserts or control, CON) of simulated
      industrial tasks in the heat (34.2 +/- 0.05  degrees C, 54.7 +/- 0.3%RH). Trials
      consisted of two 20 min work bouts, a maximum performance bout, and 10 min of
      recovery. RESULTS: Physiological strain index (PSI) was lower during PCC after
      the second work bout and during recovery (all P < 0.05). PCC reduced heat storage
      (27.0 +/- 7.6 W m-2) compared to CON (42.7 +/- 9.9 W m-2, P < 0.001). Perceptual
      strain index (PeSI) was reduced with PCC compared to CON (P < 0.001), however
      performance outcomes were not different between trials (P = 0.10). CONCLUSIONS:
      PCC during work in the heat attenuated thermal, physiological, and perceptual
      strain. This PCC garment could increase safety and reduce occupational heat
      illness risk.

PMID- 27890157
TI  - Predicting bicycle setup for children based on anthropometrics and comfort.
AB  - Bicycling is a popular activity for children. In order for children to enjoy
      cycling and to minimize injury, it is important that they are positioned
      appropriately on the bicycle. The purpose of this study was therefore to identify
      a suitable bicycle setup for children aged between 7 and 16 years which
      accommodates developmental differences in anthropometrics, flexibility and
      perceptions of comfort. Using an adjustable bicycle fitting rig, we found the
      most comfortable position of 142 children aged 7 to 16. In addition, a number of
      anthropometric measures were recorded. Seat height and the horizontal distance
      between seat and handlebars were strongly predictable (R2 > 0.999, p < 0.001 and
      R2 = 0.649, p < 0.001 respectively), whilst the predictability of the vertical
      distance between seat and handlebars was weaker (R2 = 0.231, p < 0.001). These
      results have practical implications for children and parents, paediatric
      researchers and clinicians as well as bicycle manufacturers.

PMID- 27890158
TI  - Improving our understanding of multi-tasking in healthcare: Drawing together the
      cognitive psychology and healthcare literature.
AB  - Multi-tasking is an important skill for clinical work which has received limited
      research attention. Its impacts on clinical work are poorly understood. In
      contrast, there is substantial multi-tasking research in cognitive psychology,
      driver distraction, and human-computer interaction. This review synthesises
      evidence of the extent and impacts of multi-tasking on efficiency and task
      performance from health and non-healthcare literature, to compare and contrast
      approaches, identify implications for clinical work, and to develop an evidence
      informed framework for guiding the measurement of multi-tasking in future
      healthcare studies. The results showed healthcare studies using direct
      observation have focused on descriptive studies to quantify concurrent multi
      tasking and its frequency in different contexts, with limited study of impact. In
      comparison, non-healthcare studies have applied predominantly experimental and
      simulation designs, focusing on interleaved and concurrent multi-tasking, and
      testing theories of the mechanisms by which multi-tasking impacts task efficiency
      and performance. We propose a framework to guide the measurement of multi-tasking
      in clinical settings that draws together lessons from these siloed research
      efforts.

PMID- 27890159
TI  - Evaluation of a "walk-through" ladder top design during ladder-roof transitioning
      tasks.
AB  - This study evaluated the effect of an extension ladder "walk-through" top design
      on kinetic and kinematic behaviors and the outward destabilizing forces induced
      on the ladder during transitioning at elevation. Thirty-two male participants
      performed stepping tasks between a ladder top and a roof at simulated elevation
      in a surround-screen virtual-reality system. The experimental conditions included
      a "walk-through" and a standard ladder top section supported on flat and sloped
      roof surfaces. Three force platforms were placed under the ladder section and in
      the roof to measure propulsion forces during transitions. A motion measurement
      system was used to record trunk kinematics. The frictional demand at the virtual
      ladder base was also calculated. The results indicate that under optimal ladder
      setup (angle 75.5  degrees ), the frictional demand at the ladder base remains
      relatively small for all experimental conditions. Also, the "walk through" ladder
      top eased the ladder-to-roof transitions but not the roof-to-ladder transitions.

PMID- 27890160
TI  - Children's choice: Color associations in children's safety sign design.
AB  - Color has been more identified as a key consideration in ergonomics. Color
      conveys messages and is an important element in safety signs, as it provides
      extra information to users. However, very limited recent research has focused on
      children and their color association in the context of safety signs. This study
      thus examined how children use colors in drawing different safety signs and how
      they associate colors with different concepts and objects that appear in safety
      signs. Drawing was used to extract children's use of color and the associations
      they made between signs and colors. The child participants were given 12
      referents of different safety signs and were asked to design and draw the signs
      using different colored felt-tip pens. They were also asked to give reasons for
      their choices of colors. Significant associations were found between red and
      'don't', orange and 'hands', and blue and 'water'. The child participants were
      only able to attribute the reasons for the use of yellow, green, blue and black
      through concrete identification and concrete association, and red through
      abstract association. The children's use of color quite differs from that shown
      in the ISO registered signs. There is a need to consider the use of colors
      carefully when designing signs specifically for children. Sign designers should
      take children's color associations in consideration and be aware if there are any
      misunderstandings.

PMID- 27890161
TI  - Primary or secondary tasks? Dual-task interference between cyclist hazard
      perception and cadence control using cross-modal sensory aids with rider
      assistance bike computers.
AB  - This research investigated the risks involved in bicycle riding while using
      various sensory modalities to deliver training information. To understand the
      risks associated with using bike computers, this study evaluated hazard
      perception performance through lab-based simulations of authentic riding
      conditions. Analysing hazard sensitivity (d') of signal detection theory, the
      rider's response time, and eye glances provided insights into the risks of using
      bike computers. In this study, 30 participants were tested with eight hazard
      perception tasks while they maintained a cadence of 60 +/- 5 RPM and used bike
      computers with different sensory displays, namely visual, auditory, and tactile
      feedback signals. The results indicated that synchronously using different sense
      organs to receive cadence feedback significantly affects hazard perception
      performance; direct visual information leads to the worst rider distraction, with
      a mean sensitivity to hazards (d') of -1.03. For systems with multiple
      interacting sensory aids, auditory aids were found to result in the greatest
      reduction in sensitivity to hazards (d' mean = -0.57), whereas tactile sensory
      aids reduced the degree of rider distraction (d' mean = -0.23). Our work
      complements existing work in this domain by advancing the understanding of how to
      design devices that deliver information subtly, thereby preventing disruption of
      a rider's perception of road hazards.

PMID- 27890162
TI  - Understanding emergency workers' behavior and perspectives on design and safety
      in the workplace.
AB  - Emergency Medical Services (EMS) is a demanding and hazardous industry. Because
      of the changing roles in the emergency response system, EMS workers are
      increasingly expected to provide treatment and care in addition to transport,
      which increases their task load and susceptibility to harm. This paper serves to
      outline the EMS field from the worker's perspective with the purpose of
      understanding their views on health, safety, and the work environment, and
      identify where gaps in worker well-being are exposed. Through direct observation,
      field studies, and formal interviews with EMS professionals, we discuss where
      reluctance lies in addressing safety issues and the current efforts to address
      them. A high prevalence of responses regarding the inadequacy of ambulance
      restraining systems was reported, as existing interventions do not take into
      account medic needs.

PMID- 27890163
TI  - Dissuasive exit signage for building fire evacuation.
AB  - This work presents the result of a questionnaire study which investigates the
      design of dissuasive emergency signage, i.e. signage conveying a message of not
      utilizing a specific exit door. The work analyses and tests a set of key features
      of dissuasive emergency signage using the Theory of Affordances. The variables
      having the largest impact on observer preference, interpretation and
      noticeability of the signage have been identified. Results show that features
      which clearly negate the exit-message of the original positive exit signage are
      most effective, for instance a red X-marking placed across the entirety of the
      exit signage conveys a clear dissuasive message. Other features of note are red
      flashing lights and alternation of colour. The sense of urgency conveyed by the
      sign is largely affected by sensory inputs such as red flashing lights or other
      features which cause the signs to break the tendencies of normalcy.

PMID- 27890164
TI  - The effects of interruption similarity and complexity on performance in a
      simulated visual-manual assembly operation.
AB  - The objective of the study was to assess the effects of interruption task
      similarity and complexity on performance of a simulated industrial assembly
      operation. Eighteen participants performed a simulated industrial assembly
      operation, including one trial with no interruption and eight others presenting
      an interruption task. Interruption conditions comprised a full crossing of task
      similarity to the primary assembly operation (similar, dissimilar) and complexity
      (simple, complex) with replication for each participant. Order of condition
      presentation was randomized. Findings revealed greater time to return to primary
      visual-manual assembly performance after a similar task interruption. Results
      also indicated complex interruptions may promote cognitive arousal that increases
      productivity following assembly interruptions. The majority of results are
      explained in terms of the Activation-Based Memory for Goals model. Findings
      provide some guidance for interruption management protocol design for workers
      engaged in procedural visual-manual assembly operations.

PMID- 27890165
TI  - Defining Activity Pacing: Is It Time to Jump Off the Merry-Go-Round?

PMID- 27890166
TI  - Response to Andrews and Deen on Defining Activity Pacing.

PMID- 27890167
TI  - Vaccines and Disease-Modifying Antirheumatic Drugs: Practical Implications for
      the Rheumatologist.
AB  - Patients with rheumatoid arthritis are highly vulnerable to infections because of
      abnormalities in their immune system, and because of immunosuppressive effects of
      their medications. Vaccinations in this population are complicated by disease
      modifying antirheumatic drugs, which also modulate or suppress the immune system
      and potentially decrease the immunogenicity and efficacy of the vaccines. We
      review the available data regarding the impact of rheumatoid arthritis therapy on
      the immunogenicity of various common vaccines. We also review rheumatoid
      arthritis-specific vaccination recommendations, live vaccine safety concerns, and
      current gaps in our understanding of these issues."

PMID- 27890168
TI  - Incidence and Prevention of Herpes Zoster Reactivation in Patients with
      Autoimmune Diseases.
AB  - Herpes zoster is the reactivation of latent varicella zoster virus usually
      occurring decades after initial exposure, and manifesting as a painful vesicular
      rash occurring along one or more dermatomes. Zoster incidence increases with age
      as cell mediated immunity against latent virus wanes. Epidemiological evidence
      suggests that individuals with underlying rheumatic diseases are at increased
      risk for zoster. It remains unclear whether this is due to immunosuppressive
      medications or from immune dysregulation of the underlying disease. A vaccine
      against zoster is available for individuals 50 years and older. Theoretical risks
      remain about using this live-attenuated virus vaccine in immunosuppressed
      individuals.

PMID- 27890169
TI  - Hepatitis C Virus Infection and Rheumatic Diseases: The Impact of Direct-Acting
      Antiviral Agents.
AB  - Chronic hepatitis C virus (HCV) infection is associated with liver and
      extrahepatic complications, including B-cell lymphoma, cardiovascular and kidney
      diseases, glucose metabolism impairment and rheumatic conditions ie, arthralgia,
      myalgia, cryoglobulinemia vasculitis, sicca syndrome and the production of
      autoantibodies. The treatment has long been based on interferon alpha (IFN) that
      was found poorly effective, and contraindicated in many autoimmune/inflammatory
      disorders because of possible exacerbation of rheumatic disorders. The recent
      emergence of new oral IFN-free combinations offers an opportunity for HCV
      infected patients with autoimmune/inflammatory disorders to be cured with a short
      treatment duration and low risk of side effects.

PMID- 27890170
TI  - Hepatitis B Reactivation in Rheumatic Diseases: Screening and Prevention.
AB  - Hepatitis B virus (HBV) reactivation (HBVr) has been an increasingly recognized
      and appreciated risk of immunosuppressive therapies in rheumatic patients.
      Despite its potential for significant morbidity and mortality, HBVr is a fully
      preventable complication with appropriate pretreatment screening and close
      monitoring of susceptible patients. Better knowledge of the risk for HBVr with
      the different antirheumatic agents and the establishment of the new-generation
      oral antivirals in clinical practice has greatly improved the design of screening
      and therapeutic algorithms. In this review, all available data regarding HBVr in
      rheumatic patients are critically presented and a screening and therapeutic
      algorithm is proposed.

PMID- 27890171
TI  - Barriers to Immunizations and Strategies to Enhance Immunization Rates in Adults
      with Autoimmune Inflammatory Diseases.
AB  - For as long as there have been immunizations, there have been barriers to them.
      Immunization rates in the United States are below target. Rheumatologists and
      rheumatology practitioners need to understand the issues of immunizations in
      patients with autoimmune inflammatory disease to identify and overcome barriers
      to immunization. Several strategies for overcoming these barriers are discussed.

PMID- 27890172
TI  - Opportunistic Infections in Biological Therapy, Risk and Prevention.
AB  - Patients being treated with biological therapies are at increased risk for
      serious infections, including opportunistic infections. Although more is known
      about opportunistic infection risk with older biologics, such as antitumor
      necrosis factor drugs, there is less knowledge of opportunistic infection risk
      with newer biological therapies. The incidence of certain opportunistic
      infections (tuberculosis, herpes zoster, pneumocystosis) has been rigorously
      evaluated in large observational studies. However, data are more limited for
      other infections (histoplasmosis, nontuberculous mycobacteria). Infectious
      morbidity and mortality may be preventable with screening and prophylaxis in
      select populations.

PMID- 27890173
TI  - Malignancy and the Risks of Biologic Therapies: Current Status.
AB  - Cancer is a common event in patients with rheumatic diseases. In some cases, the
      disease, its risk factors, or its treatment could play a role in favoring cancer.
      This article analyzes the current knowledge on the risk of malignancy associated
      with biologics in rheumatic diseases and discusses some methodological issues to
      be considered when evaluating the association between disease, treatments, and
      the risk of cancer. This article focuses on the risk of overall malignancy but
      also of skin cancer, lymphoma, and recurrent cancer associated with all biologics
      marketed for the treatment of rheumatic diseases.

PMID- 27890174
TI  - Immune-Related Adverse Effects of Cancer Immunotherapy- Implications for
      Rheumatology.
AB  - Immune checkpoint inhibitors (ICIs) are increasingly studied and used as therapy
      for a growing number of malignancies. ICIs work by blocking inhibitory pathways
      of T-cell activation, leading to an immune response directed against tumors. Such
      nonspecific immunologic activation can lead to immune-related adverse events
      (IRAEs). Some IRAEs, including inflammatory arthritis, sicca syndrome, myositis,
      and vasculitis, are of special interest to rheumatologists. As use of ICIs
      increases, recognition of these IRAEs and developing treatment strategies will
      become important. In this review, the current literature on rheumatic and
      musculoskeletal IRAEs is summarized. The incidence, clinical presentations, and
      treatment considerations are highlighted.

PMID- 27890175
TI  - Malignancy and Janus Kinase Inhibition.
AB  - The use of biologics such as anti-tumor necrosis factor and oral Janus kinase
      inhibitors have revolutionized the treatment of rheumatoid arthritis (RA). The
      risk of malignancies such as lymphomas, lung cancer, and nonmelanoma skin cancers
      (NMSCs) is greater in patients with RA compared with the general population. The
      incidence of all malignancy (excluding NMSC) was similar in tofacitinib users
      compared with the general population. The rates of overall and site-specific
      malignancies in patients with RA treated with tofacitinib are similar to what is
      expected in the RA population and not different from disease-modifying
      antirheumatic drugs and biologics.

PMID- 27890176
TI  - The Risk of Progressive Multifocal Leukoencephalopathy in the Biologic Era:
      Prevention and Management.
AB  - Progressive multifocal leukoencephalopathy (PML) is a rare, typically fatal,
      demyelinating central nervous system infection caused by reactivation of the John
      Cunningham virus that generally occurs in immunosuppressed patients. With an
      evolving understanding of a greater clinical heterogeneity of PML and significant
      implications for therapy, PML should be considered in the differential diagnosis
      of neurologic presentations of rheumatic diseases. Increased awareness of PML
      among rheumatologists is required, as earlier diagnosis and restoration of immune
      function may improve the otherwise grim prognosis associated with PML.

PMID- 27890177
TI  - Infection and Malignancy in Rheumatic Diseases.

PMID- 27890178
TI  - Infection and Malignancy in Rheumatic Diseases.

PMID- 27890179
TI  - Expanded Endonasal Endoscopic Approaches to the Skull Base for the Radiologist.
AB  - The cranial base is a complex 3-D region that contains critical neurovascular
      structures. Pathologies affecting this region represent some of the most
      challenging lesions to manage due to difficulty with access and risk of
      significant postoperative morbidity. With the development of expanded endonasal
      endoscopic approaches, skull base surgeons use the nose and paranasal sinuses as
      a corridor to access selected ventral skull base lesions. This review discusses
      high-resolution imaging in the evaluation of patients with skull base lesions
      considered for endonasal endoscopic surgery, summarizes various expanded
      endonasal endoscopic approaches, and provides examples of commonly used expanded
      endonasal endoscopic procedures.

PMID- 27890180
TI  - Imaging of the Posterior Skull Base.
AB  - The posterior skull base can be involved by a variety of pathologic processes.
      They can be broadly classified as: traumatic, neoplastic, vascular, and
      inflammatory. Pathology in the posterior skull base usually involves the lower
      cranial nerves, either as a source of pathology or a secondary source of
      symptoms. This review will categorize pathology arising in the posterior skull
      base and describe how it affects the skull base itself and surrounding
      structures.

PMID- 27890181
TI  - Imaging of Vascular Compression Syndromes.
AB  - Trigeminal neuralgia, hemifacial spasm, vestibulocochlear neuralgia and
      glossopharyngeal neuralgia represent the most common neurovascular compression
      syndromes. Repeated vascular pulsations at the vulnerable transitional zone of
      the individual cranial nerves lead to focal axonal injury and demyelination. High
      resolution 3-D T2-weighted MR imaging is essential in detecting and mapping
      neurovascular compression for directed therapy. Knowledge of the specific nerve
      root exit, the transitional zones, and the adjacent vasculature is critical in
      proper management. Treatment options for these neurovascular compressions
      syndromes run the gamut from medical therapy to stereotactic radiosurgery to
      botulinum injections and to surgical decompression.

PMID- 27890182
TI  - Imaging of Perineural Spread in Head and Neck Cancer.
AB  - Perineural spread (PNS) of tumor is a recognized pattern of metastasis occurring
      in the head and neck. Imaging plays a critical role in identifying PNS for
      adequate staging and treatment planning. Understanding the major branches and
      pathways of cranial nerves V and VII, key anatomic landmarks, interconnections
      between these nerves, and pearls and pitfalls of PNS imaging can aid in early
      detection, appropriate therapy, and the best possible chance for cure.

PMID- 27890183
TI  - Imaging Evaluation and Treatment of Vascular Lesions at the Skull Base.
AB  - A wide range of congenital and acquired vascular entities may occur in the skull
      base. Although some are diagnosed incidentally and merit no treatment, others may
      require surgical or image-guided endovascular or percutaneous approaches for
      management. The complex anatomy of the skull base can make diagnosis challenging.
      A combination of computed tomography scans and MR imaging, and catheter
      angiography may be required for diagnosis and mapping. Endovascular treatment
      plays an important part in many of the acquired vascular lesions, such as
      vascular neoplasms and traumatic dissections/aneurysms. Endovascular treatment is
      generally considered the gold standard for the treatment of vascular shunts at
      the skull base.

PMID- 27890184
TI  - Imaging of Cerebrospinal Fluid Rhinorrhea and Otorrhea.
AB  - As the obesity epidemic grows in the United States, rhinorrhea and otorrhea from
      spontaneous cerebrospinal fluid (CSF) leaks secondary to untreated idiopathic
      intracranial hypertension are increasing in prevalence. CSF rhinorrhea and
      otorrhea should also be carefully evaluated in posttraumatic and postsurgical
      settings, because untreated CSF leaks often have serious consequences. The work
      up, diagnosis, and characterization of a CSF leak can be complex, often requiring
      a multimodality approach to optimize surgical planning. This article reviews the
      causes of CSF leaks, describes the methodology used to work up a suspected leak,
      and discusses the challenges of making an accurate diagnosis.

PMID- 27890185
TI  - High Resolution Three-Dimensional MR Imaging of the Skull Base: Compartments,
      Boundaries, and Critical Structures.
AB  - High-resolution 3D MRI of the skull base allows for a more detailed and accurate
      assessment of normal anatomic structures as well as the location and extent of
      skull base pathologies than has previously been possible. This article describes
      the techniques employed for high-resolution skull base MRI including pre- and
      post-contrast constructive interference in the steady state (CISS) imaging and
      their utility for evaluation of the many small structures of the skull base,
      focusing on those regions and concepts most pertinent to localization of cranial
      nerve palsies and in providing pre-operative guidance and post-operative
      assessment. The concept of skull base compartments as a means of conceptualizing
      the various layers of the skull base and their importance in assessment of masses
      of the skull base is discussed.

PMID- 27890186
TI  - Advanced Imaging Techniques of the Skull Base.
AB  - Although conventional imaging can depict the anatomy of the head and neck with
      exquisite detail, it often falls short in its ability to characterize tissue
      physiology and abnormality; this is especially seen in the posttherapy setting
      where benign posttreatment changes and recurrent tumors can show intense
      postcontrast enhancement and similar features on conventional imaging. Advanced
      imaging can evaluate tissue physiology and, along with conventional imaging,
      provide a more accurate assessment of the skull base. This article describes the
      technical details and clinical applications of different advanced imaging
      techniques with a primary focus on diffusion-weighted imaging.

PMID- 27890187
TI  - Imaging of Paranasal Sinuses and Anterior Skull Base and Relevant Anatomic
      Variations.
AB  - This article reviews the normal anatomy and variants of the anterior skull base
      and sinonasal cavities that are relevant to endoscopic sinus and skull base
      surgery. Radiologists should be aware of sinonasal anatomy that can be
      impediments to surgical access and increase risk of vascular or cranial nerve
      injury during surgery. Imaging features of the paranasal sinuses and anterior
      skull base pathologies are also discussed.

PMID- 27890188
TI  - Imaging of the Central Skull Base.
AB  - The skull base is a complex bony and soft tissue interface that is divided
      anatomically into compartments. This article will focus specifically on the
      central skull base, which has a complex embryologic development and anatomy.
      Multiple entities from notochord remnants, neoplasm, infection, and other
      abnormalities may occur, and imaging is critical for depicting skull base
      pathology.

PMID- 27890189
TI  - Diplopia: What to Double Check in Radiographic Imaging of Double Vision.
AB  - When patients see double with both eyes open, known as "binocular diplopia," this
      may be a harbinger of underlying life-threatening causes. This article presents
      pertinent anatomy, critical abnormality, and radiographic features that should be
      double checked for in diplopia. Key areas requiring a double check using the
      acronym VISION include Vascular, Infectious and Inflammatory, the Scalp for giant
      cell arteritis, Sphenoid and Skull base in trauma, Increased intracranial
      pressure (pseudotumor cerebri), Onset of new headaches or psychosis, and
      Neoplasm. This article reviews the pertinent abnormalities and radiographic
      imaging critical to assess in patients with diplopia.

PMID- 27890190
TI  - Imaging of the Sella and Parasellar Region.
AB  - The sella and parasellar region, found between the anterior and central skull
      base, represents the central aspect of the skull base. Given the location of the
      pituitary gland in this location, small lesions in this location may have major
      physiologic effects on the human body. This article reviews the anatomy,
      development, and pathologic processes that may involve this region.

PMID- 27890191
TI  - Skull Base Imaging in the Era of Minimal Access Surgery.

PMID- 27890192
TI  - [Distal radius fractures].

PMID- 27890193
TI  - [Treatment of intra-articular malunion of the distal radius of young active
      patients].
AB  - Management of malunion of the distal radius remains difficult. Planning of the
      correction of the articular displacement requires a comprehensive analysis by CT
      arthrography to analyze bone, cartilage and ligaments. Arthroscopy is a valuable
      tool in the context of joint trauma. In the absence of osteoarthritis, the
      correction can be carried out as early as possible in the weeks or months
      following the initial fracture. The use of locking plates allows early
      mobilization after surgery. This correction aims to prevent the development of
      secondary osteoarthritis.

PMID- 27890194
TI  - [The chondrocostal graft to treat articular distal radius malunion].
AB  - Intra-articular malunion of the distal radius in high-demand patients can be
      treated reliably with an osteocartilaginous autograft from the rib. This graft is
      simple to harvest and it is used to resurface the carpal articular surface of the
      radius.

PMID- 27890195
TI  - [Carpal malalignment following distal radius fracture].
AB  - Adaptive carpal malalignment is the consequence of malunion of the distal radius.
      Since the radial metaphysis and capitate have to be aligned, any disorientation
      of the radial epiphysis will force the proximal carpal row to adapt, as it is the
      only mobile element. There are two types of adaptation depending where the
      compensative occurs: (1) midcarpal - leading to flexion between the lunate and
      capitate, with the lunate maintaining a normal relationship with the radial
      epiphysis axis; (2) radiocarpal - combining flexion and dorsal displacement of
      the lunate relative to the axis of the radial epiphysis, with the midcarpal joint
      remaining aligned. Clinically, adaptive carpal malalignment is not the first
      reason for consultation in cases of distal radius malunion. It occurs in cases of
      moderate deformity with preserved pronation-supination in a young patient who has
      good mobility. It generates dorsal pain that may be associated with a snapping
      sensation. The diagnosis requires strict lateral X-ray views. Over time, the
      wrist becomes stiff but analgesic and is often well tolerated functionally. This
      type of deformity has not been shown to lead to osteoarthritis. Osteotomy to
      correct the malunion is the only way to treat adaptive carpal malalignment in
      active young patients who have a mobile but painful wrist.

PMID- 27890196
TI  - [Nonunion after distal radius fracture: A review].
AB  - Nonunion after distal radius fracture is rare, serious and unpredictable. The
      preferred treatment is resection of the nonunion zone followed by open reduction
      and internal fixation with autologous iliac crest bone graft. When the distal
      fragment is less than 5mm high, a dorsal plate that bridges the radiocarpal joint
      is recommended. In patients with low functional demands, radiocarpal fusion is a
      logical choice. The bone healing rate is 58% and could be improved by using a
      vascular graft. Bone healing is not synonymous with good clinical outcomes.
      Nonunion after distal radius fracture is a serious problem and the functional
      prognosis is doubtful.

PMID- 27890197
TI  - [Treatment of partial articular fractures of the distal radius in active young
      adults].
AB  - The wrist's function is at stake in young active adults with partial intra
      articular fractures of the distal radius. The high energy nature of these
      injuries, displaced fractures with risk of malunion in case of insufficient
      treatment, and associated ligament or cartilage damage all hinder the prognosis
      of these fractures. Many classification systems exist to help us analyze and in
      some cases, select a treatment. Optimal management requires a high-quality
      preoperative assessment and a precise surgical technique coupled with the use of
      arthroscopy to deal with joint and ligament injuries in the same operation.
      Devices that address the fragmented nature of these fractures provide the best
      fixation. The primary treatment goal is reduction with less 1mm intra-articular
      step-off in order to reduce the risk of secondary osteoarthritis and to treat
      associated ligament damage, which is very common and often under-estimated.
      Treating the fracture and any associated lesions during the same operation is the
      best way to ensure a good functional outcome.

PMID- 27890198
TI  - [Treatment of extra-articular distal radius fractures in active elderly
      patients].
AB  - Extra-articular distal radius fractures in active elderly patients are common and
      predominantly affect females. The high number of patients lost to follow-up
      compromises the evaluation of outcomes. Treatment aims to control the comminution
      and allow fast recovery of pre-injury activity levels. Fixation with volar
      locking plates is the gold standard. The role of bone substitutes in this type of
      injury is unclear.

PMID- 27890199
TI  - [What is the role of primary or secondary hemiarthroplasty for distal radius
      fractures in independent elderly patients?]
AB  - The authors report their experience with wrist hemiarthroplasty for acute
      irreparable distal radius fractures in independent elderly patients (12 women,
      mean age 76years) and following failed initial treatment in the same population
      (5 women, mean age 75years). The first 11 cases have a mean follow-up of
      30months. No complications requiring implant removal were reported. At follow-up,
      the mean VAS for pain was 1/10, the mean flexion-extension arc was 60 degrees ,
      the Lyon Wrist score was 73 % and the PRWE (Patient-Related Wrist Evaluation) was
      22 points. The five patients who had secondary procedures and were reviewed at
      mean of 16months' follow-up did not require implant removal but there was one
      complete forearm rotational ankylosis with ossification. At follow-up, the mean
      VAS for pain was 3/10, the mean flexion-extension arc was 56 degrees , the Lyon
      Wrist score was 65 % and the PRWE was 45 points. The authors believe that
      hemiarthroplasty is a useful salvage procedure for irreparable wrist fractures in
      the emergency room and after failed initial treatment in active elderly patients.

PMID- 27890200
TI  - [Are there any indications for surgery of distal radius malunion in elderly
      patients?]
AB  - Malunions of the distal radius are associated most of the time with disturbances
      of the distal radioulnar (DRU) joint. While a corrective osteotomy of the distal
      radius is a well-known procedure in younger patients, manual workers and active
      patients, is it justified in independent elderly patients above 70 years of age?
      These techniques improve function, reorient the articular surfaces, protect
      against complications such as degenerative osteoarthritis and stiffness of the
      wrist, and they improve DRU balance. Osteotomies performed with bone or
      artificial grafts have comparable outcomes. Either a volar or dorsal approach can
      be used depending on the orientation of the carpal articular surface of the
      radius and the need to lengthen the radius. If the patient is active and
      independent, the clinical benefit is higher when an osteotomy is done for
      significant malunions; urgent treatment of these older patients brings about
      additional costs and unclear benefits.

PMID- 27890201
TI  - [Complex pain regional syndrome after distal radius fractures].
AB  - Complex regional pain syndrome (CPRS) greatly affects the outcomes of distal
      radius fractures in terms of functional recovery, time away from work and patient
      satisfaction. The diagnosis is sometimes difficult to make in the immediate post
      injury period. The disproportionate nature of the pain in the absence of
      differential diagnoses and the presence of a pain-free interval should arouse
      suspicion. The natural history consists of spontaneous improvement except in some
      refractory forms. The treatment is multidisciplinary combining a physician
      specializing in pain, therapist and psychologist coordinated by the surgeon who
      must not abandon the patient. Treatment aims to improve the patient's comfort and
      quality of life. Recent treatment approaches aimed at improving cortical
      reorganization have demonstrated their effectiveness. Surgery has to be
      considered even in the acute phase to address any causes of pain that can be
      resolved and address secondary stiffness. Significant progress has to be made in
      our understanding of the pathogenesis of CPRS to improve treatment and shift this
      condition to a regional pain syndrome.

PMID- 27890202
TI  - [Radiological analysis of acute distal radius fractures and clinical outcomes].
AB  - Radiological analysis of acute distal radius fractures (DRF) begins with the
      initial AP and lateral X-ray views. A CT scan is very often indicated. In
      addition to the three standard planes, 3D reconstructions are mandatory. We
      recommend not only AP views of the distal facets of the radius but also a
      complete 3D view in the surgical position. The distal ulna and carpus should also
      be analyzed. We describe the radiological sequence and the criteria used. These
      criteria are recorded in the one-page PAF chart, since they all impact the
      treatment choice. Clinical outcomes of DRF treatment are rarely addressed in the
      literature. We review the most commonly used clinical scores and describe the one
      that we use currently.

PMID- 27890203
TI  - [Distal radius fractures in children].
AB  - Metaphyseal and physeal fractures of the distal radius are common in children.
      Most cases are best treated with closed reduction and cast immobilization. Long
      term outcomes of these injuries are excellent when specific treatment principles
      of reduction and casting are followed. Surgical indications are limited and
      include open fractures, intra-articular fractures, non-reducible fractures,
      unstable fractures, and the presence of associated nerve injury. Closed reduction
      and percutaneous pin fixation is the most commonly used surgical option. The
      clinician should be aware of delayed complications such as growth disturbance of
      the distal radius, and understand how to manage these problems to ensure
      successful long-term outcomes. Epiphysiodesis is uncommon but growth plate
      injuries need to be followed for one year.

PMID- 27890204
TI  - [Hand rehabilitation after distal radius fracture].
AB  - Distal radius fractures (DRF) are common. Good outcomes are the result of
      appropriate initial treatment (immobilization, external fixation, percutaneous
      pinning or open reduction and internal fixation) and rehabilitation adapted to
      this treatment. When started immediately, rehabilitation of DRF prevents
      complications due to immobilization, surgery and a non-controlled healing
      process. Splints play an important role at all stages of rehabilitation.

PMID- 27890205
TI  - [Internal fixation of the distal radius: Medical liability considerations].
AB  - Fixation of distal radius fractures is now the primary surgical procedure leading
      to medical liability claims for surgeons dealing with injuries to the upper limb.
      The main reasons for incrimination are complex regional pain syndrome and an
      unfavorable progression toward malunion. Infectious problems are relatively rare
      and, in general, well controlled. The associated capsule and ligament damage can
      be underestimated at the time of the initial assessment, which points to the need
      for complementary imaging in case of doubt. The prevention of claims inevitably
      requires a judicious choice of the fixation technique, which is adapted to the
      anatomical fracture type and to the patient. The best defense is a complete
      medical record, with emphasis on traceable information.

PMID- 27890206
TI  - [Distal radius fractures: Which classification is the right one?]
AB  - None of the classification systems for distal radius fractures is ideal. However
      a validated system to analyze these fractures is available that is based on the
      "metaphysis, epiphysis, ulna" (MEU) classification and the "patient, accident,
      fracture" (PAF) system. It makes it possible to understand the injury and select
      the best treatment.

PMID- 27890207
TI  - [The MEU classification system for distal radius fractures: Prognostic and
      therapeutic value of an independent assessment of various fracture parameters].
AB  - Distal radius fractures (DRF) are often complex injuries that can impact the
      radial metaphysis (M), the radial epiphysis (E) and the distal ulna (U). Each of
      these parameters can influence the outcome. In a given injury, these three DRF
      components are involved to a varying degree and are variably associated. The MEU
      classification independently analyzes the three main bone components of the
      fracture; thus, all possible combinations and each specific injury can be
      described. It accurately depicts the type and severity of the DRF. Our results
      show that this classification is useful for both prognosis and treatment. The
      criteria are simple and easy to determine, making the system reliable and
      reproducible. The classification system uses rigorous and validated criteria to
      define fracture instability: any fracture for which M>2 and/or E>2 (severe
      fracture) is more likely to be associated with secondary displacement, DRUJ pain,
      and patient dissatisfaction. Furthermore, a metaphyseal fracture entering the
      DRUJ (M') and the presence of a displaced ulnar fracture (U>1) affect the
      functional outcome, thus these two features must also be included in the
      classification system.

PMID- 27890208
TI  - [Descriptive, radiographic, topographic and functional anatomy applied to distal
      radius fractures].
AB  - Extensive anatomical knowledge is needed in order to correctly treat distal
      radius fractures: normal and pathological osteology of the distal radius, distal
      radio-ulnar joint and radiocarpal joint-both on the descriptive and functional
      level-the neurovascular and muscular environments of the distal radius-which are
      essential to the surgical approaches-and the angles that need to be restored
      during the reduction. All of these concepts are broached in this article.

PMID- 27890209
TI  - [Patient-Accident-Fracture (PAF) classification of distal radius fractures].
AB  - Despite the huge amount of literature devoted to acute distal radius fractures,
      there is currently no consensus as to treatment recommendations. There is no
      universally accepted anatomical classification other than the three main
      categories of the AO classification. The authors believe that the only way to
      improve this field is to stratify the patients according to their general health
      and functional needs. They propose a new classification system that they have
      used since 2009 and demonstrate its therapeutic, epidemiological and teaching
      values.

PMID- 27890210
TI  - [Surgical exposures for distal radius fractures].
AB  - This is a review of the various approaches that can be used for open reduction
      and internal fixation (ORIF) of distal radius fractures. The main dissection
      steps are exposed and the specific indications for each approach are described.
      The anterior approach is discussed extensively as it is now the gold standard for
      ORIF of distal radius fractures. The lateral and posterior approaches are also
      described as they are sometimes needed for complex fractures.

PMID- 27890211
TI  - [Extra-articular distal radius fractures in young adults].
AB  - Extra-articular distal radius fractures in young active patients are typically
      the result of sport injuries or traffic accidents. Displaced fractures are less
      well tolerated in young patients than in older people, especially in terms of
      dorsal tilt and radial shortening. Non-surgical treatment is only indicated when
      the fracture is minimally or not displaced. No fracture fixation method is
      superior to another, however, the treatment goal is a rapid return to previous
      activities.

PMID- 27890212
TI  - [Complete intra-articular distal radius fractures in young active patients].
AB  - Management of complex intra-articular fractures of the distal radius in young
      active patients must aim to restore normal anatomy. For optimal planning of the
      surgical procedure, a thorough analysis of the fracture with appropriate
      radiological exams and diagnosis of frequently associated lesions are necessary.
      Surgical management involves use of various types of internal or external
      fixation. Routine use of standardized analysis tools for these fractures along
      with prospective follow-up should allow us to define guidelines for each
      situation in the near future.

PMID- 27890213
TI  - [Combined scaphoid and distal radius fractures in adults].
AB  - Although isolated distal radius and scaphoid fractures are common, the
      combination of both fractures is rare, with a reported frequency between 0.5% and
      6%. This rarity is probably due to the fact that both fractures share the same
      injury mechanism. Published studies are limited, but most patients are males in
      their 40s and the injuries are typically due to high-energy trauma. In most
      studies, the distal radius fracture is displaced while the scaphoid fracture is
      not. Since the functional outcome depends of the severity of the radius fracture,
      we believe, as do others, that it is logical to fix both fractures with stable
      devices (i.e., screw fixation for the scaphoid, locking plate for the radius) to
      allow for early rehabilitation.

PMID- 27890214
TI  - [Pathology of the triangular fibrocartilaginous complex in distal radius
      fractures].
AB  - Distal radius fracture is actually quite rarely isolated and triangular
      fibrocartilaginous complex (TFCC) is often involved with the same mechanism of
      injury. A contemporary management of the treatment of the initial fracture is
      ideal and so benefits from a routine arthroscopic management. Nevertheless, in
      the absence of diagnosis and therefore early treatment, the symptoms may be
      located at the ulnar crossroads and justify specific treatment of TFCC. It is
      generally conducted after an accurate arthroscopic lesion classification guiding
      a procedure, depending on the lesion vascularization as well as its possible
      destabilization potential (debridement, capsular suture or foveal reattachment).
      Unfortunately, too often the radius fracture is insufficiently stabilized by an
      inadequate fixation process or inappropriate orthopedic management with a
      positive ulnar variance consequence and an ulnar plus syndrome. A "wafer
      procedure" may then sometimes be proposed if a shortening of less than 3mm is
      needed and that the distal radio-ulnar joint is not too disorganized.

PMID- 27890215
TI  - [Incidence of distal ulna fractures associated with distal radius fractures:
      Treatment options].
AB  - Fractures of the neck and/or head of the ulna or distal ulna fracture (DUF) other
      than ulnar styloid fractures can occur in combination with distal radius
      fractures (DRF). This combination can have a significant influence on the
      treatment and prognosis since it causes the entire distal forearm to be unstable.
      In a series of 1279 consecutive unilateral DRFs, we found an associated ulnar
      neck fracture in 5.9% of cases, ulnar head and neck fracture in 1.6%, and
      isolated ulnar head fracture in 1.4%. Overall, 9% of cases in this study had a
      DUF with a DRF. The frequency of extra-articular "A" (11%) and intra-articular
      "C" (9%) DRFs according to the AO classification was about the same. There were
      no cases of DUF combined with partial "B" DRF. There was a correlation between
      combined DUF with DRF and the patient's group in the PAF classification. DUF are
      more frequently associated with DRF in elderly patients. Specific distal ulnar
      locking plates were recently introduced and they may be a useful adjunct to
      distal radius locking plates when treating patients with combined DUF and DRF.

PMID- 27890216
TI  - [Nerve injuries associated with distal radius fractures].
AB  - Nerve damage is a common complication of distal radius fractures. It may be a
      result of the injury event or be iatrogenic. It is the source of disability and
      potential handicap. There is little published data on this topic and no study has
      validated the strategies needed to prevent or manage these nerve-related
      complications. There is no consensus on treatment. Prevention requires a good
      knowledge of the various surgical approaches and rigorous fracture fixation
      technique. The objective of this article is to take stock of recent data from the
      scientific literature.

PMID- 27890217
TI  - [Outcomes of minimally invasive plate osteosynthesis (MIPO) with volar locking
      plates in distal radius fractures: A review].
AB  - Minimally invasive plate osteosynthesis (MIPO) has been used in recent years to
      treat fractures of the distal radius with volar locking plates. Its advantages
      are the preservation of the pronator quadratus and good esthetics. The MIPO
      technique was described originally with two incisions: one distal transverse or
      longitudinal incision and one proximal longitudinal incision. The trend is now to
      use a single longitudinal incision less than 20mm long. Functional and
      radiological outcomes are comparable to those of conventional techniques. The
      MIPO technique is indicated for extra-articular and intra-articular fractures.
      Arthroscopy may be used concurrently in the latter case. When the distal radius
      fracture is associated with a proximal shaft fracture, a double incision is
      needed to introduce a longer plate. The relative contraindications of the MIPO
      technique are comminuted intra-articular fractures in osteoporotic elderly
      patients. If reduction is problematic, a larger incision can easily be made.

PMID- 27890218
TI  - [Is external or internal distraction useful for treating distal radial
      fractures?]
AB  - The use of external fixation or internal plating to bridge communitive fractures
      of the distal radius is discussed based on a review of prospective and meta
      analysis studies. Distraction by an external fixator is not advised
      (ligamentotaxis) because of the high incidence of complex regional pain syndrome
      and the destabilization of bone and ligaments surrounding the intra-articular
      fracture site. The external fixator must be used as a neutralization device and
      supplemented with K-wire or volar plate fixation.

PMID- 27890219
TI  - [Over-reduction after distal radius fracture pinning in young active patients:
      Prevention by multiple mixed pinning].
AB  - Over-reduction is a classical complication following pinning of distal radius
      fractures. Indeed, the pinning techniques derived from Kapandji's technique do
      not allow anterior stabilization. A literature review and our experience show
      that it is an underestimated complication that can affect up to one-third of
      cases, but that is well tolerated if the anterior tilt is less than 20 degrees .
      Excessive angulation of the dorsal intrafocal K-wires becomes a significant risk
      factor beyond 60 degrees . Volar comminution of the fracture is an obvious
      predisposing factor. We will outline our ideas on the topic and present a new
      pinning technique, which has reduced the over-reduction rate to below 3 %:
      multiple mixed pinning combines two dorsal intrafocal K-wires with two trans
      styloid K-wires along the anterior and posterior cortices of the radius to
      provide true sagittal stabilization of the fracture. This technique is suitable
      for fractures without major instability or associated anterior comminution
      Milliez types 1 and 2 are its best indications. In our practice, there still is a
      place for pinning of non-complex fractures in young active subjects. More than 20
      degrees  malunion in flexion can lead to symptoms; in this instance, isolated
      opening osteotomy of the radius is the most suitable technique.

PMID- 27890220
TI  - [Complications of volar locking plates used to treat distal radius fractures].
AB  - About 10 years after volar locking plates were introduced to treat acute distal
      radius fractures, several papers have reported short-term complications. The aim
      of this paper was to report our complication rate over a 2-year period and to
      compare it to the literature. We found similar complication rates despite
      different classification systems. Because of the prospective nature of our study,
      we were able to demonstrate that extra-articular and/or intra-articular scores
      exceeding 8 points on a 12-points scale were statistically associated with more
      complications, irrespective of the patient's overall health and age.

PMID- 27890221
TI  - [Treatment of distal radius extra-articular malunion in young active patients].
AB  - Malunion is a common complication of distal radius fractures despite new fixation
      devices. The authors discuss the surgical indications, preoperative management
      and the various surgical techniques used to treat distal radius extra-articular
      malunion, specifically in active young subjects. The treatment goals in this
      population group are anatomical restoration of the distal radius and distal
      radioulnar joint, short immobilization period, quick functional recovery and
      stable results over time, consistent with high functional demands.

PMID- 27890222
TI  - Multiple imputation as a flexible tool for missing data handling in clinical
      research.
AB  - The last 20 years has seen an uptick in research on missing data problems, and
      most software applications now implement one or more sophisticated missing data
      handling routines (e.g., multiple imputation or maximum likelihood estimation).
      Despite their superior statistical properties (e.g., less stringent assumptions,
      greater accuracy and power), the adoption of these modern analytic approaches is
      not uniform in psychology and related disciplines. Thus, the primary goal of this
      manuscript is to describe and illustrate the application of multiple imputation.
      Although maximum likelihood estimation is perhaps the easiest method to use in
      practice, psychological data sets often feature complexities that are currently
      difficult to handle appropriately in the likelihood framework (e.g., mixtures of
      categorical and continuous variables), but relatively simple to treat with
      imputation. The paper describes a number of practical issues that clinical
      researchers are likely to encounter when applying multiple imputation, including
      mixtures of categorical and continuous variables, item-level missing data in
      questionnaires, significance testing, interaction effects, and multilevel missing
      data. Analysis examples illustrate imputation with software packages that are
      freely available on the internet.

PMID- 27890224
TI  - New Frontiers in Biomaterials.
AB  - Scientific and technological advances have combined to lead the way into a new
      era of the ever-developing science of biomaterials and tissue regeneration. This
      field has rapidly grown and new frontiers have quickly been established. Despite
      obtaining satisfactory results with current methods, improved techniques that
      lead to diminished patient discomfort, more favorable long-term prognosis, and
      decreased health care costs continue to be the goals of researchers, patients,
      and surgeons. Biomaterials have undergone a rapid evolution from materials that
      simply replaced tissues to factors that stimulate a biological response in the
      body.

PMID- 27890223
TI  - Basic Principles of Bioengineering and Regeneration.
AB  - In a quest to provide best-quality treatment, results, and long-term prognosis,
      physicians must be well versed in emerging sciences and discoveries to more
      favorably provide suitable options to patients. Bioengineering and regeneration
      have rapidly developed, and with them, the options afforded to surgeons are ever
      expanding. Grafting techniques can be modified according to evolving knowledge.
      The basic principles of bioengineering are discussed in this article to provide a
      solid foundation for favorable treatment and a comprehensive understanding of the
      reasons why each particular treatment available can be the most adequate for each
      particular case.

PMID- 27890225
TI  - Applications of Mesenchymal Stem Cells in Oral and Craniofacial Regeneration.
AB  - The field of tissue engineering and regenerative medicine has been rapidly
      expanded through multidisciplinary integration of research and clinical practice
      in response to unmet clinical needs for reconstruction of dental, oral, and
      craniofacial structures. The significance of the various types of stem cells,
      specifically mesenchymal stem cells derived from the orofacial tissues, ranging
      from dental pulp stem cells to periodontal ligament stem cells to mucosa/gingiva
      has been thoroughly investigated and their applications in tissue regeneration
      are outlined in this article.

PMID- 27890226
TI  - Tissue Engineering for Vertical Ridge Reconstruction.
AB  - This article provides an overview of basic tissue engineering principles as they
      are applied to vertical ridge defects and reconstructive techniques for these
      types of deficiencies. Presented are multiple clinical cases ranging from office
      based dentoalveolar procedures to the more complex reconstruction of
      postresection mandibular defects. Several different types of regenerative tissue
      constructs are presented; either used alone or in combination with traditional
      reconstructive techniques and procedures, such as maxillary sinus augmentation,
      Le Fort I osteotomy, and microvascular free tissue transfer. The goal is to also
      familiarize the reconstructive surgeon to potential future strategies in vertical
      alveolar ridge augmentation.

PMID- 27890227
TI  - Emerging Biomaterials in Trauma.
AB  - Emerging technologies and research into the science of biomaterials have
      developed exponentially and provide facial reconstructive surgeons with a
      plethora of options for a multitude of varying presentations. This article
      presents a comprehensive discussion in the ever-evolving field of material
      science and emerging biomaterials. A complete understanding of the current status
      of such materials is necessary for the appropriate incorporation and
      applicability to adequate clinical situations. The rapid progress seen in
      biomaterials is evidenced through the forward direction of bioengineered tissues,
      the incorporation of growth factors in varying scenarios, and the unique
      characteristics of 3-D printing of patient specific scaffolds.

PMID- 27890228
TI  - Tissue Engineered Prevascularized Bone and Soft Tissue Flaps.
AB  - The complex shapes of skeletal components of the craniofacial region combined
      with the prominence of the face and paucity of overlying soft tissue create
      significant challenges for the reconstructive surgeon. The in vivo bioreactor
      strategy is a promising alternative to microvascular surgical techniques that
      combines tissue engineering principles with microvascular reconstructive
      techniques to create patient-specific, prevascularized bone flaps for
      reconstruction of complex maxillofacial defects. This article discusses the use
      of traditional vascularized bone flaps; preclinical studies using the in vivo
      bioreactor approach; case reports that have attempted this novel technique; and
      future challenges and considerations in the development of patient-specific,
      prevascularized bone flaps for maxillofacial reconstruction.

PMID- 27890229
TI  - Maxillofacial Defects and the Use of Growth Factors.
AB  - The development and increase in knowledge of the benefits and applications of
      growth factors in craniofacial reconstruction adds a novel tool in the
      reconstructive surgeon's armamentarium. The use of growth factors varies
      according to presentation. Growth factors help to promote healing, angiogenesis,
      and formation of bone of improved quality and quantity. Growth factors used with
      stem cells and scaffolds provide a solution or alternative to discomfort created
      by donor autograft sites. The application and results of these growth factors are
      displayed in various examples of maxillofacial defects in this article, including
      reconstruction of a premaxillary cleft and of maxillary augmentation.

PMID- 27890230
TI  - Soft Tissue Engineering.
AB  - There is a recognized need to reconstruct and restore complex craniomaxillofacial
      soft tissues. The objective of this article is to focus on the role that tissue
      engineering/regenerative medicine can play in addressing various barriers
      (vascularity, tissue bulk, volitional control, and esthetics) and impediments
      (timing, regional applicability/dissemination, and regulation by the US Food and
      Drug Administration) to optimal tissue reconstruction of complex soft tissue
      structures. We will use the lips as an example to illustrate our points.

PMID- 27890231
TI  - Soft Tissue Regeneration Incorporating 3-Dimensional Biomimetic Scaffolds.
AB  - Soft tissue replacement and repair is crucial to the ever-developing field of
      reconstructive surgery as trauma, pathology, and congenital deficits cannot be
      adequately restored if soft tissue regeneration is deficient. Predominant
      approaches were sometimes limited to harvesting autografts, but through
      regenerative medicine and tissue engineering, the hope of fabricating custom
      constructs is now a feasible and fast-approaching reality. The breadth of this
      field includes tissues ranging from skin, mucosa, muscle, and fat and hopes to
      not only provide construct to replace a tissue but also to replace its function.

PMID- 27890232
TI  - Regeneration and Beyond.

PMID- 27890233
TI  - Establishing Tolerance to Commensal Skin Bacteria: Timing Is Everything.
AB  - Commensal bacteria live intimately and in constant dialogue with skin immune
      cells. Regulating our immune response to these bacteria is critical for skin
      homeostasis. Using a new murine model to track Staphylococcus epidermidis
      specific T cells, we found that colonization during neonatal but not adult life
      led to S.epidermidis-specific immune tolerance. This tolerance protected against
      skin inflammation and was mediated by a wave of regulatory T cells entering
      neonatal skin. These findings provide new insight into how we establish a healthy
      symbiosis with commensal microbes and highlight avenues for future research to
      identify novel therapies for inflammatory skin disease.

PMID- 27890234
TI  - Current Status of Dedicator of Cytokinesis-Associated Immunodeficiency: DOCK8 and
      DOCK2.
AB  - DOCK8 deficiency is an autosomal recessive combined immunodeficiency disease
      associated with elevated IgE, atopy, recurrent sinopulmonary and cutaneous viral
      infections, and malignancy. The DOCK8 protein is critical for cytoskeletal
      organization, and deficiency impairs dendritic cell transmigration, T-cell
      survival, and NK cell cytotoxicity. Early hematopoietic stem cell transplantation
      is gaining prominence as a definitive treatment given the potential for severe
      complications and mortality in this disease. Recently, DOCK2 deficiency has been
      identified in several patients with early-onset invasive bacterial and viral
      infections.

PMID- 27890236
TI  - The Critical and Multifunctional Roles of Antimicrobial Peptides in Dermatology.
AB  - Antimicrobial peptides are central effector molecules in skin immunology. The
      functions of antimicrobial peptides in skin diseases include the ability to act
      as cytokines or growth factors, driving disorders such as psoriasis and rosacea,
      as well as their action as natural antibiotics to control bacteria that influence
      diseases such as atopic dermatitis and acne.

PMID- 27890235
TI  - Dermatologic Manifestations of Monogenic Autoinflammatory Diseases.
AB  - Autoinflammatory disorders are sterile inflammatory conditions characterized by
      episodes of early-onset fever, rash, and disease-specific patterns of organ
      inflammation. Gain-of-function mutations in innate danger-sensing pathways,
      including the inflammasomes and the nucleic acid sensing pathways, play critical
      roles in the pathogenesis of IL-1 and Type-I IFN-mediated disorders and point to
      an important role of excessive proinflammatory cytokine signaling, including
      interleukin (IL)-1b , Type-I interferons, IL-18, TNF and others in causing the
      organ specific immune dysregulation. The article discusses the concept of
      targeting proinflammatory cytokines and their signaling pathways with cytokine
      blocking treatments that have been life changing for some patients.

PMID- 27890238
TI  - Understanding Inherited Cylindromas: Clinical Implications of Gene Discovery.
AB  - Cylindromas are cutaneous tumors first described in the medical literature over
      150 years ago. They are now known to occur on an inherited basis as a result of
      mutations in the tumor-suppressor gene CYLD. The discovery of this gene has
      provided novel insights into this rare skin tumor syndrome. As well as enabling
      genetic counseling of affected patients, the knowledge of CYLD function has led
      to steps toward development of novel therapeutics, with CYLD-regulated signaling
      pathways as the target for this approach.

PMID- 27890237
TI  - Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway.
AB  - Somatic mutations in genes of the PI3K/PTEN/AKT/TSC/mTORC1 signaling pathway
      cause segmental overgrowth, hamartomas, and malignant tumors. Mosaicism for
      activating mutations in AKT1 or PIK3CA cause Proteus syndrome and PIK3CA-Related
      Overgrowth Spectrum, respectively. Postzygotic mutations in PTEN or TSC1/TSC2
      cause mosaic forms of PTEN hamartoma tumor syndrome or tuberous sclerosis
      complex, respectively. Distinct features observed in these mosaic conditions in
      part reflect differences in embryological timing or tissue type harboring the
      mutant cells. Deep sequencing of affected tissue is useful for diagnosis. Drugs
      targeting mTORC1 or other points along this signaling pathway are in clinical
      trials to treat these disorders.

PMID- 27890239
TI  - Interleukin-22 and Cyclosporine in Aggressive Cutaneous Squamous Cell Carcinoma.
AB  - Cutaneous squamous cell carcinomas (SCCs) account for up to 10,000 deaths
      annually in the United States. Most of the more than 700,000 SCCs diagnosed are
      cured by excision with clear margins; however, metastasis can occur despite
      seemingly adequate treatment in some cases. Immune-suppressed organ transplant
      recipients are 60 to 100 times more likely to develop SCC than immune-competent
      individuals. Transplant-associated SCCs occur more frequently and behave more
      aggressively, showing higher risk of recurrence and metastasis. This article
      identifies a potential role for interleukin-22 in driving SCC proliferation,
      particularly in solid organ transplant recipients taking cyclosporine.

PMID- 27890240
TI  - Melanocytic Nevi and the Genetic and Epigenetic Control of Oncogene-Induced
      Senescence.
AB  - Melanocytic nevi represent benign clonal proliferations of the melanocytes in the
      skin that usually remain stable in size and behavior or disappear during life.
      Infrequently, melanocytic nevi undergo malignant transformation to melanoma.
      Understanding molecular and cellular mechanisms underlying oncogene-induced
      senescence should help identify pathways underlying melanoma development, leading
      to the development of new strategies for melanoma prevention and early detection.

PMID- 27890241
TI  - Distinct Fibroblasts in the Papillary and Reticular Dermis: Implications for
      Wound Healing.
AB  - Human skin wounds heal largely by reparative wound healing rather than
      regenerative wound healing. Human skin wounds heal with scarring and without
      pilosebaceous units or other appendages. Dermal fibroblasts come from 2 distinct
      lineages of cells that have distinct cell markers and, more importantly, distinct
      functional abilities. Human skin wound healing largely involves the dermal
      fibroblast lineage from the reticular dermis and not the papillary dermis. If
      scientists could find a way to stimulate the dermal fibroblast lineages from the
      papillary dermis in early wound healing, perhaps human skin wounds could heal
      without scarring and with skin appendages.

PMID- 27890242
TI  - Basic Science Insights into Clinical Puzzles.

PMID- 27890243
TI  - Effect of Combination Cholesterol-Lowering Therapy and Triglyceride-Lowering
      Therapy on Medical Costs in Patients With Type 2 Diabetes Mellitus.
AB  - High triglyceride (TG) levels among patients with type 2 diabetes mellitus (DM)
      are associated with higher medical costs. We analyzed the economic impact of TG
      lowering therapies and whether the association between medical costs and therapy
      differed according to TG reduction. We conducted an observational cohort study of
      184,932 patients with diabetes mellitus who had a TG measurement between January
      2012 and June 2013 and a second TG measurement 3 to 15 months later. We
      identified 4 therapy groups (statin monotherapy, TG-specific monotherapy,
      statin/TG-specific combination therapy, or no therapy) and stratified those
      groups by percent change in TG (increased >=5%, change of <=4.9%, decreased 5% to
      29%, decreased >=30%). We compared change in medical costs between the year
      before and after therapy, adjusted for demographic and clinical characteristics.
      Of the 184,932 total patients, 143,549 (77.6%) received statin monotherapy, 900
      (0.5%) received TG-specific monotherapy, 1,956 (1.1%) received statin and TG
      specific combination therapy, and 38,527 (20.8%) received no prescription lipid
      agents. After covariate adjustment, statin/TG-specific agent recipients had a
      mean 1-year total cost reduction of $1,110. The greatest cost reduction was seen
      among statin/TG-specific combination therapy patients who reduced TG levels by
      >=30% (-$2,859). Statin monotherapy patients who reduced TG by >=30% also had a
      large reduction in adjusted costs (-$1,079). In conclusion, we found a
      substantial economic benefit to treating diabetic patients with statin/TG
      specific combination lipid therapy compared with monotherapy of either type or no
      lipid pharmacotherapy. A TG reduction of >=30% produced a particularly large
      reduction in 1-year medical costs.

PMID- 27890244
TI  - Development and Optimization of a Wet Granulation Process at Elevated Temperature
      for a Poorly Compactible Drug Using Twin Screw Extruder for Continuous
      Manufacturing.
AB  - The objective of this study was to enhance tabletability of a poorly compactible
      drug, acetaminophen, by wet granulation using twin screw extruder at high
      temperature. It was desired that there would be minimum amounts of excipients
      used and the granules obtained after extrusion would be dry and fall within a
      size range suitable for tableting without any further processing. Mixtures of
      acetaminophen (95%) with binders (5% povidone or partially pregelatinized starch)
      were wet granulated through twin screw extruder at 70 degrees C by adding 7% w/w
      water. The process had a short granulation time (<1 min), and, on account of the
      elevated processing temperature used, no drying after extrusion was needed. By
      optimizing formulation and processing parameters, >90% granules in the size range
      of 125 to 1000 MUm (<3% above 1000 MUm and <7% below 125 MUm) were obtained
      without any milling. When the granules were compressed by adding 1% disintegrant
      and 0.5% lubricant extragranularly, tablets produced (93.6% drug load) had good
      mechanical strength having hardness >1.7 MPa, which was superior to that of
      tablets prepared by conventional high shear wet granulation. As the granules
      could be extruded continuously and did not require drying and milling, the method
      was amenable to continuous processing.

PMID- 27890246
TI  - Treatment of dynamic scapholunate instability dissociation: Contribution of
      arthroscopy.
AB  - Scapholunate (SL) ligament injuries generally result from trauma to an extended,
      supinated wrist, leading to chronic instability that progresses toward
      osteoarthritis. They can occur together with distal radius fracture. These
      injuries can be difficult to diagnose, especially early on. Treating chronic SL
      ligament injuries before the onset of osteoarthritis is still a challenge for
      surgeons. Until recently, the recommended treatments consisted of open SL
      ligament reconstruction or repair procedures that reduce pain and improve pinch
      strength but also lead to wrist stiffness. The introduction of arthroscopy has
      completely changed our understanding of these injuries and how to treat them. We
      review here the treatment approach through the eyes of three specific groups of
      surgeons: the "pioneers" who first analyzed these injuries; the "specialists" who
      explored various stabilization techniques to compensate for the torn SL ligament;
      and the most recent group, the "anatomists" who, based on recent arthroscopy
      findings, sought to reconstruct the anatomical structures as accurately as
      possible and who developed the concept of the SL complex.

PMID- 27890245
TI  - Mathematical Models for Controlled Drug Release Through pH-Responsive Polymeric
      Hydrogels.
AB  - Hydrogels consisting of weakly charged acidic/basic groups are ideal candidates
      for carriers in oral delivery, as they swell in response to pH changes in the
      gastrointestinal tract, resulting in drug entrapment at low pH conditions of the
      stomach and drug release at high pH conditions of the intestine. We have
      developed 1-dimensional mathematical models to study the drug release behavior
      through pH-responsive hydrogels. Models are developed for 3 different cases that
      vary in the level of rigor, which together can be applied to predict both in
      vitro (drug release from carrier) and in vivo (drug concentration in the plasma)
      behavior of hydrogel-drug formulations. A detailed study of the effect of
      hydrogel and drug characteristics and physiological conditions is performed to
      gain a fundamental insight into the drug release behavior, which may be useful in
      the design of pH-responsive drug carriers. Finally, we describe a successful
      application of these models to predict both in vitro and in vivo behavior of
      docetaxel-loaded micelle in a pH-responsive hydrogel, as reported in a recent
      experimental study.

PMID- 27890247
TI  - Reproducibility of X-rays and CT arthrography in SLAC, SNAC, SCAC wrists.
AB  - The purpose of this study was to assess the inter-observer and intra-observer
      reproducibility of the interpretation of CT arthrography and plain X-rays for
      scapholunate advanced collapse (SLAC), scaphoid non-union advanced collapse
      (SNAC) and scaphoid chondrocalcinosis advanced collapse (SCAC) wrist conditions,
      as well as the clinical relevance of these imaging modalities. The CT and X-rays
      images were reviewed twice in a blinded and randomized manner by two experienced
      orthopedic surgeons specialized in hand surgery, two orthopedic surgery residents
      and two experienced radiologists specialized in bone and joint imaging. Cohen's
      kappa and Fleiss' kappa coefficients were used to analyze the reproducibility of
      interpretation of the radiological examinations. With CT arthrography, the
      overall diagnosis was often a problem, in terms of both inter- or intra-observer
      reproducibility. The assessment of the joint line appeared to be fairly
      reproducible for each observer but was poorly reproducible between different
      observers. Plain X-rays are not sufficient to assess cartilage quality in
      degenerative wrist disease. CT arthrography is a reliable examination, but its
      interpretation is not always standardized. Diagnostic arthroscopy may be
      justified in doubtful cases.

PMID- 27890248
TI  - Proximal row carpectomy on manual workers: 17 patients followed for an average of
      6 years.
AB  - : Proximal row carpectomy (PRC) is indicated for the treatment of SNAC or SLAC
      wrist with preservation of the midcarpal joint. Our hypothesis was that PRC is
      not appropriate for treating advanced wrist osteoarthritis in patients who carry
      out heavy manual work. Twenty-three PRCs were performed on 21 patients, 5 women
      and 16 men with an average age of 54 years (33-77). All patients performed manual
      work; 11 of them performed heavy manual work. Etiologies were: SLAC wrist in 14
      cases (2 stage III, 11 stage II, and 1 stage I) and SNAC wrist in 9 cases (6
      stage IIIB and 3 stage IIB). At an average 75 months' follow-up (24-153), five
      patients were lost to follow-up. Radiocarpal arthrodesis was performed in one
      patient 10 years after the PRC. In the 17 remaining patients (18 wrists), pain
      (VAS) averaged 2.2, with residual pain of 5. Flexion-extension range was similar
      to preoperative levels (67% of contralateral wrist). Wrist strength was decreased
      by 34% compared to preoperative. The QuickDASH score averaged 26 points and the
      PRWE 20 points. Radiocapitate distance decreased by 0.3mm on average with joint
      line narrowing in 6 patients. The carpal translation index was 0.33mm, which was
      unchanged relative to preoperative values. Three patients had work-related
      limitations that required retraining and one patient had to be reassigned. PRC
      preserved the preoperative range of motion and reduced pain levels. However,
      significant loss of strength was observed, resulting in 23% of manual workers
      needing retraining or reassignment. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic
      IV.

PMID- 27890249
TI  - Early outcomes of Pyrocardan(r) implants for trapeziometacarpal osteoarthritis.
AB  - The aim of this retrospective study was to assess the early outcomes of
      trapeziometacarpal osteoarthritis treatment using Pyrocardan(r) implants in
      patients with early Eaton (stage I and II) osteoarthritis. We analyzed the
      results of 27 patients, with a median age of 59 years (range, 34-78 years) and a
      mean follow-up of 24 months (range, 12-41). The level of satisfaction was
      assessed using a postoperative questionnaire. Twenty patients mentioned having
      improvements in their activities of daily living, 20 patients were satisfied with
      the outcomes of surgery, and 19 patients would consider undergoing the procedure
      a second time. Five patients needed reoperation for complications, including
      persistent pain, grinding, or implant dislocation. Pyrocardan(r) implants may be
      a valuable temporary therapy as more conventional arthroplasty techniques are
      still feasible in case of failure. However, multicenter randomized controlled
      trials with a longer follow-up are needed to assess the long-term outcomes.

PMID- 27890250
TI  - The role of self-efficiency toward pain following surgical treatment of carpal
      tunnel syndrome.
AB  - Some very poor results after carpal tunnel syndrome (CTS) surgery are difficult
      to explain. The main hypothesis of this study was that a relationship exists
      between self-efficiency toward pain and the difference between pre-operative and
      post-operative pain. The secondary hypothesis was that a relationship exists
      between self-efficiency toward pain and the pre-operative and post-operative
      QuickDASH score. The records of 64 patients operated for purely subjective CTS
      were reviewed. The evaluation consisted in determining self-efficacy beliefs from
      two PSEQ2 questions (1: I can still accomplish most of my goals in life, despite
      the pain; 2: I can live a normal lifestyle, despite the pain), pain levels and
      the QuickDASH score. There was an inversely proportional relationship between the
      pre-operative PSEQ2 and pain on one hand, and post-operative pain and the pre
      operative QuickDASH score on the other hand. We found no correlation between the
      pre-operative PSEQ2 and post-operative QuickDASH score. Self-efficiency beliefs
      as measured by PSEQ2 help to predict pain levels after surgical CTS treatment in
      the absence of sensory and/or motor deficits and/or associated morbidity.

PMID- 27890251
TI  - Partial transfer from C7 root to external branch of accessory nerve for trapezius
      palsy.

PMID- 27890252
TI  - AML in 2016: Where we are now?
AB  - A high relapse rate for patients with acute myeloid leukemia (AML) is still a
      major barrier to the long-term survival of these patients. Nevertheless,
      considerable progress has been made both in the biology and therapy of the
      disease. Specifically, progress has been made in the areas of integrated genomic
      analysis for prognosis, the widening application of minimal residual disease
      (MRD) monitoring in clinical practice, the development of new agents, and the
      increasing use of drugs, such as IDH and FLT3 inhibitors, as a bridge to
      transplant. Continued progress and inquiry into these and other areas are
      essential to improve the survival outcome for adult patients with AML.

PMID- 27890253
TI  - A cryptic translocation leading to NUP98-PHF23 fusion in AML.
AB  - Chromosome translocations leading to gene fusions have emerged as important
      oncogenic drivers of various types of malignancies. Detection and
      characterization of these fusion genes not only help diagnosis and management of
      specific malignancies, but also contribute to our understanding of the genetic
      basis and pathogenesis of these diseases. NUP98 gene encodes a 98 kDa
      nucleoporin, which is a component of the nuclear pore complex that mediates
      transport of mRNA and proteins between the nucleus and the cytoplasm. Due to its
      participation in translocations leading to the formation of fusion with at least
      29 different partner genes, NUP98 is considered one of the most promiscuous
      fusion genes in hematologic malignancies. We discuss our identification and
      characterization of a NUP98-PHF23 fusion from a cryptic translocation in patients
      with acute myeloid leukemia (AML).

PMID- 27890254
TI  - Why are there so few randomized trials for patients with primary refractory acute
      myeloid leukemia?
AB  - Fewer patients with primary refractory AML ("PREF") are entered into phase 3
      trials than are patients with relapsed AML. This is particularly noteworthy
      because data from phase 3 trials for newly diagnosed AML indicated PREF and
      relapse are equally common. Here I discuss three possible reasons for this
      discrepancy. First, there is disagreement whether the criterion for PREF AML
      should be failure of one or two courses of initial induction therapy. Second,
      there may be an impression that PREF AML is qualitatively worse than relapsed
      AML. Third, there may be a general unwillingness to randomize patients with such
      poor prognoses.

PMID- 27890256
TI  - Why the stagnation in effective therapy for MDS?
AB  - The question posed above assumes that we are going nowhere in therapies for
      myelodysplastic syndromes (MDS) and asks, why? Yet, in recent years novel and
      effective therapies for MDS indeed have begun to emerge, particularly in patients
      with lower-risk disease. Beyond this, however, most of the progress has been
      limited to advances in allogeneic transplantation for higher-risk patients. This
      discussion will focus first on areas where we have moved beyond "stagnation,"
      including these advances in supportive care for lower-risk patients and in
      emerging transplant gains. Further, in areas that have not seen the same
      encouraging advances, suggestions are made on how to move the field forward. The
      promise for the future lies in finding more creative ways to partner molecular
      genetics, novel drugs, and novel clinical trial designs.

PMID- 27890255
TI  - Chimeric antigen receptor T cell therapy in AML: How close are we?
AB  - The majority of patients presenting with acute myeloid leukemia (AML) initially
      respond to chemotherapy but post-remission therapy is required to consolidate
      this response and achieve long-term disease-free survival. The most effective
      form of post-remission therapy relies on T cell immunotherapy in the form of
      allogeneic hematopoietic cell transplantation (HCT). However, patients with
      active disease cannot usually expect to be cured with HCT. This inherent
      dichotomy implies that traditional T cell-based immunotherapy in the form of
      allogeneic HCT stops being efficacious somewhere between the measurable residual
      disease (MRD) and the morphologically obvious range. This is in part because the
      full power of T cells must be restrained in order to avoid lethal graft-versus
      host disease (GVHD) and partly because only a sub-population of donor T cells are
      expected to be able to recognize AML cells via their T cell receptor. Chimeric
      antigen receptor (CAR) T cell therapy, most advanced in the treatment of patients
      with B-cell malignancies, may circumvent some of these limitations. However,
      major challenges remain to be overcome before CAR T cell therapy can be safely
      applied to AML.

PMID- 27890257
TI  - Is there justification for 4 cycles of consolidation therapy in AML?
AB  - The concept of postremission therapy in acute myeloid leukemia is quite old,
      dating back to a trial conducted in 1988 by the Cancer and Leukemia Group B. Yet
      even with more than 20 years of investigation into the optimal number of cycles
      for consolidation therapy, the answer is still not entirely clear. Dose intensity
      also has an impact on the number of courses of consolidation therapy
      administered, as do the cytogenetics of the patients. This review examines how to
      direct the future of consolidation therapy outside of allogeneic transplantation
      and discusses the issues to consider in choosing the number of courses of
      consolidation, including the effect minimal residual disease may have in guiding
      decisions regarding consolidation treatment.

PMID- 27890258
TI  - Should anyone with Philadelphia chromosome-positive ALL who is negative for
      minimal residual disease receive a hematopoietic stem cell transplant in first
      remission?
AB  - Outcomes for patients with Philadelphia chromosome-positive acute lymphoblastic
      leukemia (Ph+ ALL) in the pre-imatinib era were poor, particularly if patients
      did not receive an allogeneic hematopoietic stem cell transplant. This led to the
      recommendation that all patients with Ph+ ALL, if they were transplant
      candidates, should be transplanted. With the introduction of imatinib and
      subsequently other tyrosine kinase inhibitors, patient outcomes improved
      dramatically, raising the question of whether transplant in first complete
      molecular remission for these patients is really necessary. This review looks at
      evidence from clinical studies around the world in an attempt to answer this
      question.

PMID- 27890260
TI  - The role of second transplants for leukemia.
AB  - Management of relapsed leukemia following allogeneic transplantation is
      challenging. Intensive chemotherapy, donor lymphocyte infusions (DLI), or second
      transplantation have some value, but most reported series describe only a limited
      number of patients surviving beyond 2 or 3 years following relapse. Additionally,
      understandable selection-bias of reports describing the outcomes of intensive
      management approaches for relapsed leukemia confound generalizability to a
      broader population. However numerous reports suggest that second allogeneic
      transplantation for relapsed leukemia following an initial transplant may produce
      extended disease control and survival for patients with favorable performance
      status, remission at the time of second transplant, and most importantly a long
      interval between initial transplant and relapse. Reduced intensity conditioning
      for second allografts may be preferable and little data exists to suggest that a
      new donor will improve disease control by inducing a stronger graft-versus
      leukemia effect. Improved measures to prevent the first relapse, however, may
      protect more patients and produce a greater fraction enjoying extended leukemia
      free survival.

PMID- 27890261
TI  - Consolidation chemotherapy prior to hematopoietic cell transplantation for adults
      with acute myeloid leukemia in first remission.
AB  - Whether patients with acute myeloid leukemia (AML) should receive routine
      consolidation chemotherapy prior to transplant remains a significant question.
      Consolidation therapy may be advisable in the face of transplant delays, such as
      donor identification, insurance clearance, or transplant center scheduling, to
      prevent relapse prior to transplant. However, in cases where physicians have a
      choice, the question of the value of consolidation chemotherapy continues to be
      debated. This paper reviews the value of consolidation therapy in 4 different
      transplant settings.

PMID- 27890259
TI  - How important is NK alloreactivity and KIR in allogeneic transplantation?
AB  - Relapse of acute myelogenous leukemia (AML) after allogeneic hematopoietic cell
      transplantation (allo HCT) is a major cause of death in transplant recipients.
      Efforts to control relapse by promoting donor T-cell alloreactivity, such as
      withdrawal of immune suppression or donor lymphocyte infusions, are limited by
      the propensity to induce graft versus host disease (GVHD) and by inadequate
      efficacy. Therefore, options for AML patients who have relapsed AML after allo
      HCT are few and outcomes are poor. Similar to T-cells, natural killer (NK) cells
      have potent anti-leukemia effector capacity, and yet unlike T-cells, NK cells do
      not mediate GVHD. Furthermore, their function does not require matching of human
      leukocyte antigens (HLA) between donor and recipient. Maximizing donor NK
      alloreactivity thus holds the exciting possibility to induce the graft versus
      leukemia (GVL) effect without engendering GVHD. Among the array of activating and
      inhibitory NK cell surface receptors, the killer Ig-like receptors (KIR) play a
      central role in modulating NK effector function. Here we will review how KIR
      mediates donor alloreactivity, discuss the role of KIR gene and allele typing to
      optimize allo HCT donor selection, and discuss how KIR may aid adoptive NK and
      other cell therapies.

PMID- 27890262
TI  - What is the role of novel thrombopoietic agents in the management of acute
      leukemia?
AB  - The role of novel thrombopoietic agents in the management of acute leukemia is a
      tale of two molecules, romiplostim and eltrombopag. Both are thrombopoietin (TPO)
      receptor agonists with somewhat different mechanisms of action. Romiplostim is a
      peptide TPO receptor agonist that activates the TPO receptor by binding to it
      just like TPO. Eltrombopag is a nonpeptide TPO receptor agonist that activates
      the TPO receptor by binding to the transmembrane domain. Both TPO receptor
      agonists increase platelet counts in healthy humans and in those with immune
      thrombocytopenia. This review focuses on the potential these agents may have in
      supportive care of patients with acute leukemia.

PMID- 27890263
TI  - Innate immunity and the new forward genetics.
AB  - As it is a hard-wired system for responses to microbes, innate immunity is
      particularly susceptible to classical genetic analysis. Mutations led the way to
      the discovery of many of the molecular elements of innate immune sensing and
      signaling pathways. In turn, the need for a faster way to find the molecular
      causes of mutation-induced phenotypes triggered a huge transformation in forward
      genetics. During the 1980s and 1990s, many heritable phenotypes were ascribed to
      mutations through positional cloning. In mice, this required three steps. First,
      a genetic mapping step was used to show that a given phenotype emanated from a
      circumscribed region of the genome. Second, a physical mapping step was
      undertaken, in which all of the region was cloned and its gene content
      determined. Finally, a concerted search for the mutation was performed. Such
      projects usually lasted for several years, but could produce breakthroughs in our
      understanding of biological processes. Publication of the annotated mouse genome
      sequence in 2002 made physical mapping unnecessary. More recently we devised a
      new technology for automated genetic mapping, which eliminated both genetic
      mapping and the search for mutations among candidate genes. The cause of
      phenotype can now be determined instantaneously. We have created more than
      100,000 coding/splicing mutations. And by screening for defects of innate and
      adaptive immunity we have discovered many "new" proteins needed for innate immune
      function.

PMID- 27890264
TI  - Selective suppression of in situ proliferation of scyphozoan polyps by
      biofouling.
AB  - An increase in marine artificial constructions has been proposed as a major cause
      of jellyfish blooms, because these constructions provide additional substrates
      for organisms at the benthic stage (polyps), which proliferate asexually and
      release a large amount of free-swimming medusae. These hard surfaces are normally
      covered by fouling communities, the components of which have the potential to
      impede the proliferation of polyps. In this study, we report an in situ
      experiment of polyp survival of four large scyphozoan species found in East Asian
      marginal seas that were exposed to biofouling, a universal phenomenon occurring
      on marine artificial constructions. Our results showed that the polyps of three
      species (Nemopilema nomurai, Cyanea nozaki, and Rhopilema esculentum) attached to
      the artificial surfaces were completely eliminated by biofouling within 7
      8months, and only those of moon jellyfish (Aurelia sp.1) in the upper layers
      could multiply on both artificial materials and other organisms (e.g., ascidians
      and bryozoans). Fouling-associated competition and predation and suppressed
      asexual reproduction of podocysts were observed to contribute to the loss of
      polyps. This study shows that the natural distribution of polyps is defined by
      the biofouling community that colonizes the surfaces of artificial constructions.
      Consequently, the contribution of marine constructions to jellyfish bloom is
      limited only to the ability of the jellyfish species to reproduce asexually
      through budding and inhabit solid surfaces of fouling organisms in addition to
      inhabiting original artificial materials. We anticipate that fragile polyps will
      colonize and proliferate in harsh environments that are deleterious to
      biofouling, and we propose special attention to polyps in antifouling practices
      for excluding the possibility that they occupy the available ecological space.

PMID- 27890265
TI  - Review of "Rebuttal to published article "A review of ghost gear entanglement
      amongst marine mammals, reptiles and elasmobranchs" by M. Stelfox, J. Hudgins,
      and M. Sweet."

PMID- 27890266
TI  - ?

PMID- 27890267
TI  - [The silence of a body and speech set free].
AB  - Anorexia is a reflection of issues with the body in all its states. The social
      body and the representation of a model's body, mistreated in order to meet
      certain standards, the medical body shaken by the mystery of anorexia, and the
      subjective body and the reality of the flesh. The anorexic body is a testament to
      a past full of pain and neglect, a sign of emotional deficiency. Caring for the
      body of a person with anorexia, whatever the approach, means also and above all
      working with the future of a human being.

PMID- 27890268
TI  - [All the bodies of anorexia].
AB  - Anorexia is an active struggle against hunger. In this fight, the body is a real
      battlefield where the therapies used aim to re-establish peace. Hence the
      importance of an integrative 'body to body' approach between patient and
      caregiver.

PMID- 27890269
TI  - [Anorexia and borderline personality disorder : bonds pathology].
AB  - Comorbidity with a borderline personality disorder is far from rare in patients
      suffering from eating disorders. Clinically, this presents as chronic instability
      in many areas: interpersonal relationships, self-image, emotions, mood and acting
      out. Treatment is mainly based on a containing and reassuring therapeutic
      framework. A care plan may be put in place that incorporates reducing impulsive
      harmful, eating and self-harming behaviours. Dialectical behaviour therapy is
      intended in particular to prevent suicide risk in borderline personality disorder
      patients.

PMID- 27890270
TI  - [Anorexia in males].
AB  - Anorexia nervosa is often considered as a women disease, whereas 10% of the cases
      are men. There are much more researches in this field for a couple of decades.
      "Bigorexia", which combines food control and need for muscles, seems to be more
      frequent above men.

PMID- 27890271
TI  - [Towards a transcultural approach to eating disorders].
AB  - Anorexia must not be considered as a syndrome specific to a culture but as being
      linked to fast-moving sociocultural changes. Its occurrence can be favoured by
      certain transcultural phenomena, such as globalisation and the process of
      acculturation. The analysis of a clinical case of a young migrant with anorexia
      illustrates the complexity and need for complementary transcultural
      psychotherapy, to improve understanding and the future.

PMID- 27890272
TI  - [My stomach, the monster under my bed].
AB  - Care for patients with eating disorders is complex and plurimodal. Care plans
      need to be adapted in order to take into account the body in crisis. A series of
      hospital admissions combined with specific psychomotor approaches, can contribute
      to the patient being reappropriated with their own body.

PMID- 27890273
TI  - [Care pathway for teenagers with anorexia].
AB  - Identifying a care pathway for a teenager with anorexia enables the therapeutic
      stages to be put into perspective. From prevention to full hospitalisation, from
      the general practitioner to the paediatrician or child psychiatrist, this
      harmonisation aims to help the patient feel safe at every level of the care
      pathway.

PMID- 27890274
TI  - [Treating the somatic complications of anorexia].
AB  - Anorexia can cause serious somatic complications, linked to undernutrition or
      associated pathological behaviours. The care pathway drawn up by a multi
      discipline team is a real therapeutic challenge. Oral nutritional supplements,
      enteral nutrition and parenteral nutrition are three possible forms of
      nutritional assistance.

PMID- 27890275
TI  - [Organising nutritional support for patients with anorexia].
AB  - Nutritional care in the Eating Disorder unit of Sainte-Anne general hospital in
      Paris, is organised around a care model based on cognitive behavioural therapy.
      Hospitalisation is generally prepared beforehand and aims to draw on patients'
      resources enabling them to clarify a request for help. A care contract can be
      drawn up to provide step-by-step support for the patient in terms of the goals to
      achieve.

PMID- 27890276
TI  - Quand le trauma s'intrique avec l'anorexie mentale.
AB  - A person having suffered traumatic life events may find relief in the formation
      of symptoms. Anorexia can therefore be envisaged as a way of facing up to the
      trauma, both as a means of positioning oneself, as well as a solution for
      relieving the traumatic suffering. However, giving up these symptoms is sometimes
      difficult, as the case of Lea demonstrates.

PMID- 27890277
TI  - [Nursing care of body image disorders].
AB  - Anorexia causes body image disorders. The re-appropriation and acceptance of the
      body and its changes require specific care. Mirrors, 'morphing' software,
      photography, videography and the trying on of clothes in a store are tools which
      can help the patient reconstruct themselves.

PMID- 27890278
TI  - ?

PMID- 27890279
TI  - Of mice and women - Non-ovarian origins of "ovarian" cancer.

PMID- 27890280
TI  - Prevention of venous thromboembolism in gynecologic oncology surgery.
AB  - Gynecologic oncology patients are at a high-risk of postoperative venous
      thromboembolism and these events are a source of major morbidity and mortality.
      Given the availability of prophylaxis regimens, a structured comprehensive plan
      for prophylaxis is necessary to care for this population. There are many
      prophylaxis strategies and pharmacologic agents available to the practicing
      gynecologic oncologist. Current venous thromboembolism prophylaxis strategies
      include mechanical prophylaxis, preoperative pharmacologic prophylaxis,
      postoperative pharmacologic prophylaxis and extended duration pharmacologic
      prophylaxis that the patient continues at home after hospital discharge. In this
      review, we will summarize the available pharmacologic prophylaxis agents and
      discuss currently used prophylaxis strategies. When available, evidence from the
      gynecologic oncology patient population will be highlighted.

PMID- 27890281
TI  - Corrigendum to 'Treatment outcomes in patients with FIGO stage IB-IIA cervical
      cancer and a focally disrupted cervical stromal ring on magnetic resonance
      imaging: A propensity score matching study' [Gynecol. Oncol. 143 (2016) 77-82].

PMID- 27890282
TI  - Selective versus non-selective his bundle pacing for cardiac resynchronization
      therapy.
AB  - Cardiac resynchronization therapy (CRT) has an established role in the device
      based therapy for patients with systolic dysfunction and intraventricular
      conduction delay, particularly left bundle branch block (LBBB). Recently, His
      bundle pacing (HBP) has emerged as a viable alternative for resynchronization
      which can successfully narrow surface QRS and improve mechanical dyssynchrony.
      The role of selective (i.e., an isoelectric His-paced to QRS interval similar to
      native HV interval) versus non-selective capture (i.e., engagement of His along
      with adjacent local myocardial tissue and pseudo-delta wave) and outcome after
      HBP for resynchronization is not clear. In this article, we review the current
      literature (case reports and case series) reporting on HBP for resynchronization
      and comment on favorable predictors of response.

PMID- 27890284
TI  - [Fibulin-5, a new potential therapeutic target in AAA].

PMID- 27890283
TI  - The 4th Report of the Working Group on ECG diagnosis of Left Ventricular
      Hypertrophy.
AB  - The 4th Report provides a brief review of publications focused on the
      electrocardiographic diagnosis of left ventricular hypertrophy published during
      the period of 2010 to 2016 by the members of the Working Group on ECG diagnosis
      of Left Ventricular Hypertrophy. The Working Group recommended that ECG research
      and clinical attention be redirected from the estimation of LVM to the
      identification of electrical remodeling, to better understanding the sequence of
      events connecting electrical remodeling to outcomes. The need for a re-definition
      of terms and for a new paradigm is also stressed.

PMID- 27890285
TI  - Invertebrate Oncology: Diseases, Diagnostics, and Treatment.
AB  - Neoplasia is a documented occurrence across invertebrate taxa, but challenges
      remain with regard to tumor diagnosis and treatment. Literature reports of
      neoplasia are frequent in mollusks and insects, infrequent in Cnidaria and
      crustaceans, and are yet to be documented in Porifera and echinoderms. A
      significant contribution could be made by veterinary practitioners documenting
      and treating neoplasms in invertebrates. Traditional methods of veterinary
      diagnosis are encouraged, but the anatomy and tissue biology of each invertebrate
      species need to be considered. Most neoplasms described in the invertebrate
      literature have been considered benign, making external lesions potentially
      amenable to surgical resection.

PMID- 27890286
TI  - Rodent Oncology: Diseases, Diagnostics, and Therapeutics.
AB  - Cancer incidence in rodent species varies dramatically from a common occurrence
      in mice and rats to just a limited number of documented cases in chinchillas and
      degus. This article summarizes common tumors, both benign and malignant, that
      have been reported to occur in rodents. Outlined are clinical signs, diagnostics,
      and treatments that have been described for rodents presenting with specific
      neoplasms.

PMID- 27890287
TI  - Rabbit Oncology: Diseases, Diagnostics, and Therapeutics.
AB  - Neoplasia has long been reported as a rare finding in rabbits, but over the past
      decades the number of reports on neoplastic disease in rabbits has risen
      considerably. Similar to other animals, neoplastic changes may occur in any organ
      system, but the rate in which the organ systems are affected differs
      considerably. In rabbits, tumors have predominantly been found in the urogenital,
      hemolymphatic, and integumentary systems. This article discusses current insights
      on the etiopathogenesis, clinical signs, diagnosis, and treatment of the
      commonest neoplastic diseases in rabbits and offer guidelines for the correct
      diagnosis and treatment of the rabbit oncologic patient.

PMID- 27890288
TI  - Ferret Oncology: Diseases, Diagnostics, and Therapeutics.
AB  - Neoplastic disease is common in ferrets. Approximately half of all tumors
      diagnosed in ferrets are located in the endocrine or hemolymphatic system. Many
      factors may influence the choice of treatment. Medical management of adrenal
      tumors has a greater disease-free period compared to adrenalectomy. In ferrets
      with an insulinoma, no difference is seen in the mean survival time of medically
      and surgically treated patients. Aside from medical and surgical treatment
      modalities, chemotherapy and radiation therapy have also been described in
      ferrets in other types of tumors. The outcome of these treatment modalities is
      not always favorable.

PMID- 27890289
TI  - Principles and Applications of Medical Oncology in Exotic Animals.
AB  - Diagnoses of neoplasia in exotic animals have historically been made at death or
      just before euthanasia. Routine physical examinations are enabling early
      diagnosis while accessibility and affordability of advanced diagnostics are
      improving. With increasing expectations for care, treatment options are more
      frequently explored. Numerous oncologic medications have been adopted from human
      and small animal medicine and successfully used in exotic animals. Although there
      is a need for extended research, this article evaluates which medications have
      been used thus far for treatment protocols in zoologic and exotic animal species.

PMID- 27890290
TI  - Fish Oncology: Diseases, Diagnostics, and Therapeutics.
AB  - The scientific literature contains a wealth of information concerning spontaneous
      fish neoplasms, although ornamental fish oncology is still in its infancy. The
      occurrence of fish neoplasms has often been associated with oncogenic viruses and
      environmental insults, making them useful markers for environmental contaminants.
      The use of fish, including zebrafish, as models of human carcinogenesis has been
      developed and knowledge gained from these models may also be applied to
      ornamental fish, although more studies are required. This review summarizes
      information available about fish oncology pertaining to veterinary clinicians.

PMID- 27890291
TI  - Principles and Applications of Surgical Oncology in Exotic Animals.
AB  - The diagnosis and treatment of cancer in exotic species is a rapidly evolving
      area of veterinary medicine. In general, surgical excision remains pivotal in
      cancer treatment, although optimal outcomes are achieved when a coherent and
      thorough diagnostic and therapeutic plan is created prior to surgery. While
      surgical cure is not always achieveable, multimodal treatment plans can offer a
      variety of options, and palliative procedures may be used to improve quality of
      life. Treatment goals, whether curative intent or palliative intent, should be
      identified before surgery, and practitioners should endeavor to adhere to
      surgical principles in order to attain the best outcomes.

PMID- 27890292
TI  - Principles and Applications of Radiation Therapy in Exotic Animals.
AB  - Radiation therapy is a treatment modality for cancer that is widely used in
      veterinary medicine, although its use in exotic animal practice has remained
      limited. However, there are case reports and case series of treating birds, small
      mammals, and reptiles for a variety of cancers with radiotherapy with varied
      outcomes. In this article the basic principles of radiation therapy are reviewed
      and the literature regarding its use in exotic animal practice is summarized.
      Side effects of radiotherapy are also discussed.

PMID- 27890293
TI  - Avian Oncology: Diseases, Diagnostics, and Therapeutics.
AB  - Companion birds are increasingly living longer due to improved husbandry,
      nutrition, and veterinary care. As a consequence, a growing number of geriatric
      disease conditions are diagnosed and managed by veterinarians. Awareness of bird
      owners of diagnostic and treatment options for neoplastic diseases in humans and
      domestic animals has led to increasing demand to provide advanced diagnostic and
      treatment modalities for companion birds diagnosed with neoplasia. Treatment
      remains challenging in many companion birds due to the lack of information
      regarding prognosis and efficacy of antineoplastic treatments in these species.
      There is no established standard of care for most tumors in companion birds.

PMID- 27890294
TI  - Oncology of Reptiles: Diseases, Diagnosis, and Treatment.
AB  - Based on necropsy review, neoplasia in reptiles has a comparable frequency to
      that of mammals and birds. Reptile neoplasia is now more frequently diagnosed in
      clinical practice based on increased use of advanced diagnostic techniques and
      improvements in reptilian husbandry allowing greater longevity of these species.
      This article reviews the current literature on neoplasia in reptiles, and focuses
      on advanced diagnostics and therapeutic options for reptilian patientssuffering
      neoplastic disease. Although most applied clinical reptile oncology is translated
      from dog and cat oncology, considerations specific to reptilian patients commonly
      encountered in clinical practice (turtles, tortoises, snakes, and lizards) are
      presented.

PMID- 27890295
TI  - Exotic Animal Oncology.

PMID- 27890296
TI  - Analytic solutions for colloid transport with time- and depth-dependent retention
      in porous media.
AB  - Elucidating and quantifying the transport of industrial nanoparticles (e.g.
      silver, carbon nanotubes, and graphene oxide) and other colloid-size particles
      such as viruses and bacteria is important to safeguard and manage the quality of
      the subsurface environment. Analytic solutions were derived for aqueous and solid
      phase colloid concentrations in a porous medium where colloids were subject to
      advective transport and reversible time and/or depth-dependent retention. Time
      dependent blocking and ripening retention were described using a Langmuir-type
      equation with a rate coefficient that respectively decreased and increased
      linearly with the retained concentration. Depth-dependent retention was described
      using a rate coefficient that is a power-law function of distance. The stream
      tube modeling concept was employed to extend these analytic solutions to
      transport scenarios with two different partitioning processes (i.e., two types of
      retention sites). The sensitivity of concentrations was illustrated for the
      various time- and/or depth-dependent retention model parameters. The developed
      analytical models were subsequently used to describe breakthrough curves and, in
      some cases, retention profiles from several published column studies that
      employed nanoparticle or pathogenic microorganisms. Simulations results provided
      valuable insights on causes for many observed complexities associated with
      colloid transport and retention, including: increasing or decreasing effluent
      concentrations with continued colloid application, delayed breakthrough, low
      concentration tailing, and retention profiles that are hyper-exponential,
      exponential, linear, or non-monotonic with distance.

PMID- 27890297
TI  - Digesting the role of bone marrow macrophages on hematopoiesis.
AB  - Tissue resident macrophages are found in various tissues like Langerhans cells in
      the skin or alveolar macrophages in the lung, and their main function is to
      regulate organ homeostasis. They have also been observed in the bone marrow and
      these cells in particular have been gaining importance in recent years as they
      are key players in hematopoiesis. However, as the characterization and
      classification of these putatively different bone marrow resident macrophages is
      far from established there is a need to generate an overview of tissue resident
      macrophages of the bone marrow. Here, we will review the current knowledge of
      bone marrow resident macrophages both in mouse and human. We will discuss the
      state of the art on the origin of bone marrow macrophages, specialized
      microenvironments where they reside and their unique characteristics. We will
      emphasize the two best studied examples of macrophage homeostatic function in the
      bone marrow, specifically within erythroblastic islands and the hematopoietic
      stem cell niche. Although increasing evidence shows that bone marrow resident
      macrophages are indispensable for hematopoietic stem cell function and bone
      marrow erythroid output, the field of bone marrow macrophages is in its infancy.
      This field is in dire need for a unified nomenclature to support functional
      experiments, model systems, and the identification of niches.

PMID- 27890298
TI  - Heterogeneity of 90Sr radioactive contamination at the head part of the East Ural
      radioactive trace (EURT).
AB  - 1: We measured 90Sr concentrations and beta particle flux density (BPFD) in 44
      soil samples collected from four soil profiles across a central transect on the
      head of the East Ural Radioactive Trace (EURT). The relationship between BPFD and
      90Sr concentration of each soil sample can be characterised by a linear
      regression model; 90Sr concentration in the upper 12 cm soil layer can thus be
      assessed by measuring BPFD in the soil surface. 2: The BPFD on the soil surface
      was measured at 969 points at seven sites with linear dimensions ranging from 140
      * 20 m to 140 * 320 m. The correspondence of 90Sr concentration in the 12 cm soil
      layer with its BPFD value was calculated for each of these seven sites. Eighty
      (80) % of 90Sr concentration measurements in the 12 cm soil layer in each model
      site differed by a factor of 2.0-5. The variability of 90Sr concentration
      increased significantly in the 12 cm upper soil layer over territories with
      visual features of landscape disturbance (pits, trenches). The ratio of maximum
      to minimum concentration of 90Sr varied from 6.1 to 6.6 in the 12 cm soil layer
      over territories without visual features of anthropogenic soil disturbance. 3:
      The 90Sr concentration was measured in the skeletons of 34 juvenile Microtus
      oeconomus individuals weighing less than 12.5 g and trapped at the four model
      sites in July. The assessment of 90Sr concentration in the 12 cm soil layer was
      conducted for each point where an animal was trapped. The relationship between
      90Sr concentration in soil and in the skeleton was characterised by a linear
      regression model with a determination coefficient of 0.51. 4: The concentration
      ratio for 90Sr from soil to skeleton (CRskeleton-soil) was 2.0 +/- 0.1 for M.
      oeconomus over the territory of the EURT, which is consistent with the minimum
      value of the same CRskeleton-soil for M. oeconomus from the Chernobyl area
      (Chesser et al., 2000).

PMID- 27890299
TI  - Monte Carlo simulations of the gamma-ray exposure rates of common rocks.
AB  - Monte Carlo simulations have been performed to model the gamma ray emission and
      attenuation properties of common rocks. In geologic materials, 40K, 238U, and
      232Th are responsible for most gamma ray production. If the concentration of
      these radioelements and attenuation factors such as degree of water saturation
      are known, an estimate of the gamma-ray exposure rate can be made. The results
      show that there are no significant differences in gamma-ray screening between
      major rock types. If the total number of radionuclide atoms are held constant
      then the major controlling factor is density of the rock. Finally, the thickness
      of regolith or soil overlying rock can be estimated by modeling the exposure rate
      if the radionuclide contents of both materials are known.

PMID- 27890300
TI  - Evaluating clinical care in the prehospital setting: Is Rapid Emergency Medicine
      Score the missing metric of EMS?
AB  - INTRODUCTION: The Rapid Emergency Medicine Score (REMS) was developed to predict
      emergency department patient mortality. Our objective was to utilize REMS to
      assess initial patient acuity and evaluate clinical change during prehospital
      care. METHODS: All non-cardiac arrest emergency transports from April 1, 2013 to
      March 31, 2014 were analyzed from a single EMS agency. Using age, pulse rate,
      mean arterial pressure, respiratory rate, oxygen saturation, and Glasgow Coma
      Scale, initial and final REMS were calculated. Change in REMS was calculated by
      initial minus final with a positive number indicating clinical improvement.
      Descriptive analyses were performed calculating means and 95% confidence
      intervals. RESULTS: There were 61,346 patients analyzed with an average initial
      REMS of 4.3 (95% CI: 4.2-4.3) and an average REMS change of 0.37 (95% CI: 0.36
      0.38). Those patients classified with the highest dispatch priority had the
      highest initial REMS (5.8; 95% CI: 5.5-6.2) and the greatest change (0.95; 95%
      CI: 0.72-1.17). Patients transported with high priority had greater initial REMS,
      as well as greater improvement in REMS (high priority 7.3 [95% CI: 7.1-7.4],
      change 0.61 [95% CI: 0.53-0.69]; middle priority 5.3 [95% CI: 5.2-5.4], change
      0.55 [95% CI: 0.51-0.59]; low priority 3.9 [95% CI: 3.8-3.9], change 0.32 [95%
      CI: 0.31-0.33]). CONCLUSION: Descriptive analyses indicate that as dispatch and
      transport priorities increased in severity so too did initial REMS. The largest
      change in REMS was seen in patients with the highest dispatch and transport
      priorities. This indicates that REMS may provide system level insight into
      evaluating clinical changes during care.

PMID- 27890301
TI  - Thrombolytic therapy-associated acute myocardial infarction in patients with
      acute ischemic stroke: A treatment dilemma.
AB  - Acute myocardial infarction (AMI) is uncommon in the acute phase of acute
      ischemic stroke (AIS) and occurs in approximately 1% of the population. Here, we
      report a paradoxical case of AMI during tissue plasminogen activator (t-PA)
      infusion for AIS. We review and analyze the previously reported cases. We found
      that only patients with AMI which occurred after thrombolytic therapy for AIS who
      received an adequate combination of anticoagulation plus percutaneous coronary
      intervention survived their events. Several mechanisms have been proposed for the
      development of AMI after thrombolytic therapy. These mechanisms include
      fragmented intra-cardiac thrombus, intensified platelet aggregation that may lead
      to an increased potential for intra-cardiac thrombus formation, and a reduction
      in clot-associated plasminogen that may lead to a paradoxical hypercoagulable
      state of the coronary arteries. Currently, there is no consensus regarding this
      specific scenario. We propose that the therapeutic benefit and the potential risk
      of hemorrhagic complications should be further investigated and individualized.
      In patients who receive thrombolytic therapy for AIS and who then develop post
      thrombolytic AMI, we suggest that the maximum treatment for the subsequent AMI be
      instituted promptly to avoid short-term mortality.

PMID- 27890303
TI  - Cognitive effects of creatine monohydrate adjunctive therapy in patients with
      bipolar depression: Results from a randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Depressive episodes and cognitive impairment are major causes of
      morbidity and dysfunction in individuals suffering from bipolar disorder (BD).
      Novel treatment approaches that target clinical and cognitive aspects of bipolar
      depression are needed, and research on pathophysiology suggests that
      mitochondrial modulators such as the nutraceutical creatine monohydrate might
      have a therapeutic role for this condition. METHODS: Eighteen (N=18) patients
      with bipolar depression according to DSM-IV criteria who were enrollled in a 6
      week, randomized, double-blind, placebo-controlled trial of creatine monohydrate
      6g daily as adjunctive therapy were submitted to neuropsychological assessments
      (Wisconsin Card Sorting Test, Digit Span subtest of the Wechsler Adult
      Intelligence Scale-Third Edition, Stroop Color-Word Test, Rey-Osterrieth complex
      figure test, FAS Verbal Fluency Test) at baseline and week 6. RESULTS: There was
      a statistically significant difference between the treatment groups of the change
      on the total scores after 6 weeks in the verbal fluency test, with improvement in
      the group receiving adjunctive treatment with creatine. We did not find
      significant differences between the groups of the changes on other
      neuropsychological tests. LIMITATIONS: Small sample and lack of a control group
      of healthy subjects. CONCLUSIONS: Our trial, which was the first to investigate
      the cognitive effects of creatine monohydrate on bipolar depression, indicates
      that supplementation with this nutraceutical for 6 weeks is associated with
      improvement in verbal fluency tests in patients with this condition.

PMID- 27890302
TI  - [Facilitators and barriers regarding end of life care at nursing homes: A focus
      group study].
AB  - AIM: To identify the facilitators and barriers experienced by professional
      related to end of life care in nursing homes. DESIGN: Descriptive qualitative
      research with phenomenological orientation, through content analysis. PLACEMENT:
      Nursing Homes at Primary Care District in Granada (Spain). PARTICIPANTS: Fifteen
      clinical professionals with, at least 6 months of experience in nursing homes,
      without specific background in palliative care. METHODS: Three focus groups were
      undertaken with professionals of different disciplines and nursing homes.
      Interviews were recorded and transcribed literally. An open and axial coding was
      performed to identify relevant categories. RESULTS: Professionals identified
      difficulties in the communication with families related to relatives' feelings of
      guilt, difficulty in understanding the deterioration of their relative, and
      addressing too late the issue of death. Regarding decision making, professionals
      recognized that they do not encourage participation of patients. Advance
      directives are valued as a necessary tool, but they do not contemplate
      implementing them systematically. Other difficulties that professionals
      highlighted are lack of coordination with other professionals, related to
      misunderstanding of patients' needs, as well as lack of training, and lack of
      material and human resources. Facilitators include relationships with primary
      care teams. CONCLUSION: It is necessary to improve communication among nursing
      homes professionals, families, patients and other health workers.

PMID- 27890304
TI  - Awareness of goal-oriented behavior during infancy and early childhood, in human-
      and non-human primates.
AB  - We review the literature surrounding the phylogenetic and developmental emergence
      of goal-oriented behavior, among human and non-human primates. We define goal
      oriented awareness as the ability to perceive goals and perceptions in others. We
      examine empirical literature involving gaze-following, shared attention,
      distinguishing between actions and intentions, and the ability to generate and
      understand communicative cues. We conclude that at least a rudimentary awareness
      of goal-oriented behavior is present from birth in humans, and in adult great
      apes. The evidence in other primate species shows phylogenetic differences as
      well as gaps in the empirical literature.

PMID- 27890305
TI  - Capacity building for critical care training delivery: Development and evaluation
      of the Network for Improving Critical care Skills Training (NICST) programme in
      Sri Lanka.
AB  - OBJECTIVES: To deliver and evaluate a short critical care nurse training course
      whilst simultaneously building local training capacity. RESEARCH METHODOLOGY: A
      multi-modal short course for critical care nursing skills was delivered in seven
      training blocks, from 06/2013-11/2014. Each training block included a Train the
      Trainer programme. The project was evaluated using Kirkpatrick's Hierarchy of
      Learning. There was a graded hand over of responsibility for course delivery from
      overseas to local faculty between 2013 and 2014. SETTING: Sri Lanka. MAIN OUTCOME
      MEASURES: Participant learning assessed through pre/post course Multi-Choice
      Questionnaires. RESULTS: A total of 584 nurses and 29 faculty were trained.
      Participant feedback was consistently positive and each course demonstrated a
      significant increase (p<=0.0001) in MCQ scores. There was no significant
      difference MCQ scores (p=0.186) between overseas faculty led and local faculty
      led courses. CONCLUSIONS: In a relatively short period, training with good
      educational outcomes was delivered to nearly 25% of the critical care nursing
      population in Sri Lanka whilst simultaneously building a local faculty of
      trainers. Through use of a structured Train the Trainer programme, course
      outcomes were maintained following the handover of training responsibility to Sri
      Lankan faculty. The focus on local capacity building increases the possibility of
      long term course sustainability.

PMID- 27890306
TI  - [Advocacy for pediatric hospital reference centers specialized in child
      protection].

PMID- 27890307
TI  - [French society of pediatrics forensic pathology: Speciality's union to protect
      minors].

PMID- 27890308
TI  - Erratum to "A combined deficiency of tissue factor and PAR-4 is associated with
      fatal pulmonary hemorrhage in mice" [Thromb. Res. 146 (2016) 46-50].

PMID- 27890309
TI  - Patterns of Ninety-Day Readmissions Following Total Joint Replacement in a
      Bundled Payment Initiative.
AB  - BACKGROUND: Alternative payment models aim to improve quality and decrease costs
      associated with total joint replacement. Postoperative readmissions within 90
      days are of interest to clinicians and administrators as there is no additional
      reimbursement beyond the episode bundled payment target price. The aim of this
      study is to improve the understanding of the patterns of readmission which would
      better guide perioperative patient management affecting readmissions. We
      hypothesize that readmissions have different timing, location, and patient health
      profile patterns based on whether the readmission is related to a medical or
      surgical diagnosis. METHODS: A retrospective cohort of 80 readmissions out of
      1412 total joint replacement patients reimbursed through a bundled payment plan
      was analyzed. Patients were grouped by readmission diagnosis (surgical or
      medical) and the main variables analyzed were time to readmission, location of
      readmission, and baseline Perioperative Orthopaedic Surgical Home and American
      Society of Anesthesiologists scores capturing pre-existing state of health.
      Nonparametric tests and multivariable regressions were used to test associations.
      RESULTS: Surgical readmissions occurred earlier than medical readmissions (mean
      18 vs 33 days, P = .011), and were more likely to occur at the hospital where the
      surgery was performed (P = .035). Perioperative Orthopaedic Surgical Home and
      American Society of Anesthesiologists scores did not predict medical vs surgical
      readmissions (P = .466 and .879) after adjusting for confounding variables.
      CONCLUSION: Readmissions appear to follow different patterns depending on whether
      they are surgical or medical. Surgical readmissions occur earlier than medical
      readmissions, and more often at the hospital where the surgery was performed. The
      results of this study suggest that these 2 types of readmissions have different
      patterns with different implications toward perioperative care and follow-up
      after total joint replacement.

PMID- 27890310
TI  - Same Day Total Hip Arthroplasty Performed at an Ambulatory Surgical Center: 90
      Day Complication Rate on 549 Patients.
AB  - BACKGROUND: There is an increasing interest in outpatient total hip arthroplasty
      (THA), as there are perceived benefits to the patient, insurer, and overall
      healthcare system. However, the safety of outpatient total joint arthroplasty has
      not been studied. METHODS: Five hundred forty-nine patients who underwent mini
      posterior THA at a freestanding independent ambulatory surgical center (ASC) were
      reviewed. All patients were discharged to home on the day of surgery. RESULTS:
      The average age of the patients was 54.4 years (range 27-73). The average
      American Society of Anesthesiologists score was 1.6 (range 1-3). Of the 549
      patients, 3 (0.5%) admitted from the surgery center to our local hospital. One
      patient was admitted for pain control after failing to disclose his long-term
      high-dose narcotic dependence, one patient was admitted for an acetabular
      component migration identified on postoperative x-ray, and one patient was
      admitted for hypotension, bradycardia, and an acute polyarthralgia exacerbation.
      An additional patient was seen 2 days after surgery in a local emergency
      department for oversedation secondary to narcotics and later discharged to home.
      CONCLUSION: Outpatient THA at an ASC is safe and effective when performed on the
      appropriately indicated patient. There were 4 visits to the hospital within 2
      days of surgery. Only 1 was related to medical events, 2 were pain control and/or
      medication-related and the final was technique-related. Known orthopedic
      complications including infection, dislocation, and deep vein thrombosis appear
      consistent with the literature for a series of this size. Same day discharge THA
      in an ASC is safe and reproducible.

PMID- 27890311
TI  - Letter to Editor regarding flawed method in Nursing Outlook systematic review.

PMID- 27890312
TI  - Variables associated with loss of ileoanal pouches constructed in childhood.
AB  - AIMS: To quantify the incidence of loss of an ileoanal pouch in children and to
      identify variables associated this event. METHODS: Logistic regression of
      possible explanatory variables: age, sex, indication for procto-colectomy, pre
      operative continence status, use of immunosuppressive drugs, open or laparoscopic
      surgery, number of stages, anastomotic leak, operative complication excluding
      anastomotic leak, performance of revisional surgery, albumin concentration and
      platelet count at time of surgery, rank order in series. Univariate logistic
      regression was used to identify significant variables which were then assessed in
      a multivariate model and construction of Kaplan-Meier graphs. RESULTS: 103
      children, 56 girls, underwent ileoanal pouch at median age 14years (SD 3.7).
      Indications and mean age were: ulcerative colitis (n=71, 14years), polyposis
      syndromes (n=13, 15years), chronic idiopathic constipation (n=9, 11years),
      Hirschsprung's disease (n=4, 1year), Crohn's disease (n=2, 16years), and
      fibrosing colonopathy (n=2, 11years). 13 patients had their pouch excised or
      permanently diverted. Three patients had successful revisional pouch surgery.
      Only pre-operative fecal incontinence and anastomotic leak were significantly
      associated with pouch excision/diversion, however on multivariate analysis, only
      fecal incontinence remained significant, odds ratio 21 (95%CI 1.8-235, p=0.01).
      Pouch survival was significantly worse where there was fecal incontinence pre
      operatively, p<0.0001 or an anastomotic leak, p<0.001. CONCLUSIONS: 13% of
      children subjected to restorative procto-colectomy ultimately receive a permanent
      ileostomy. Fecal incontinence prior to surgery is a relative contra-indication.
      Anastomotic leak increases the probability of later pouch excision. LEVEL OF
      EVIDENCE: IV.

PMID- 27890313
TI  - Laparoscopic fundoplication in neonates and young infants: Failure rate and need
      for redo at a high-volume center.
AB  - AIM OF THE STUDY: Present the outcomes of patients younger than 2years who
      underwent laparoscopic fundoplication, highlighting the failure rate and need for
      redo fundoplication. METHODS: Retrospective review of patients <2years who
      underwent laparoscopic fundoplication between January 2009 and December 2014.
      MAIN RESULTS: 458 infants younger than 2years underwent laparoscopic
      fundoplication in the 6-year period (360 Nissen, 77 Toupet and 21 Thal
      fundoplications). Median age at surgery was 5 (1-23) months. Median follow-up was
      3 (1-6) years. The conversion rate was 0.87% (4 of 458 cases). Patients did not
      undergo routine studies to assess the incidence of postoperative GER but were
      instead followed clinically. Failure of the fundoplication was determined when a
      patient was unable to gain weight and/or protect the airway while receiving
      gastric feedings because of GER. The failure rate in our experience was 2.6% (12
      redo out of 458 cases [11/360 Nissen, 1/77 Toupet and 0/21 Thal]). All failed
      cases occurred because of migration of the fundoplication, confirmed
      preoperatively by a contrast study. Median time between the initial
      fundoplication and the redo was 13 (5-27) months. There were no failures within a
      contemporaneous group of 101 patients <2years who underwent open fundoplication.
      CONCLUSION: The need for a redo fundoplication after a laparoscopic
      fundoplication was an uncommon event in our experience (12 of 458 cases). Our
      results contrast with published studies that report higher failure rates. Case
      volume per surgeon may explain in part the dissimilar results among studies.
      LEVEL OF EVIDENCE: III.

PMID- 27890314
TI  - Endoscopic surgery in children - the challenge goes on.
AB  - : Paediatric endoscopic surgery is greatly indebted to Karl Storz for developing
      paediatric endoscopic instruments. In more recent years, there is an increasing
      interest in endoscopic surgery in neonates. Now more complex procedures are being
      performed, although it will take another generation before these will be more
      generally applied. One of the key factors to success is training. More
      sophisticated training models are becoming available, allowing practicing in a
      safe environment before putting the procedure to practice. A key question in
      performing complex procedures is whether such procedures should not be
      concentrated into centres of expertise. Finally, a critical appraisal is
      warranted in regard to safety of surgery in neonates, as they fail to have
      cerebral autoregulation. As endoscopy may add additional risk factors, close
      monitoring is obligatory. LEVEL OF EVIDENCE: V.

PMID- 27890315
TI  - Global surgery: A view from the south.
AB  - : This article is based on the Hugh Greenwood Lecture delivered at the 2016
      Congress of the British Association of Paediatric Surgeons. It presents the view
      of the global surgery movement from the bottom of the surgical food chain and
      proposes what HICs (high-income countries) can do for global surgery in a
      coordinated fashion. From the LMIC (low- and middle-income countries) surgeon
      perspective, global surgery is transitioning from the charity-based surgery model
      to codevelopment with multiple stakeholders. The caveats and current
      opportunities are described using two case studies. Surgeons may not play a
      pivotal role in the solutions. The future of the surgical workforce, innovation,
      workarounds, unmet burden of disease, and health metrics are discussed and
      multidisciplinary solutions proposed for the entire chain of surgical healthcare
      delivery in LMIC. A new breed of "essential surgeons", technology solutions for
      intellectual and physical isolation, competency-based credentialing, industry
      driven innovation, task sharing over task shifting, prioritizing delivery based
      on surgical burden, and a rota-based overseas model of help are proposed as
      solutions for the issues facing global surgery. EVIDENCE LEVEL: Level V.

PMID- 27890316
TI  - Is there a dependence between children's body weight and the concentration of
      metals in deciduous teeth?
AB  - Malnutrition, manifested by both overweight and underweight, can lead to serious
      health consequences. The subject of the study was to determine the concentration
      of elements such as chromium (Cr), calcium (Ca), copper (Cu), iron (Fe) and
      manganese (Mn) in children's deciduous teeth in relation to their body weight.
      The calculated body mass index (BMI) values and an application of the growth
      chart showed that 59% of children among the studied sample had normal weight. In
      41% of children, weight disorders were observed including underweight - 28% and
      overweight - 12%. Median concentration of metals in deciduous teeth was:
      3.79MUgMn/g, 52.2MUgFe/g, 4.73MUgCu/g, 10.7MUgCr/g, 36.1%Ca/g. There were no
      statistically significant differences in the concentration of the studied metals
      in the teeth of children with normal and abnormal body weight. However, the
      dependence between the metals in teeth varied with the children's weight. This
      may suggest changes in the mineral composition of tissues that are associated
      with metabolic disorders.

PMID- 27890317
TI  - Supernumerary heads to biceps brachii muscle and Asian population history.
AB  - Supernumerary heads of biceps brachii are one of the most common anatomic
      variants in the muscular system and appear to develop under genetic control and
      vary in prevalence among populations. Variation in prevalence and morphology
      therefore has the potential to contribute to understanding of human population
      history. Until now, there has been no publication of the prevalence of the
      variant in Southeast Asian populations. The aim of this research is to document
      the prevalence and morphology of the variant in a sample of Thai cadavers and to
      consider the significance of the findings. The method used was dissection of arms
      of 162 donated cadavers at Khon Kaen University, Thailand. The sample showed high
      prevalence of third heads of biceps brachii in 35% of cadavers, compared with the
      prevalence of up to 25% reported in large samples worldwide. The sample also
      showed equal prevalence in males and females and one-third present bilaterally.
      This pattern is similar to that found in East Asia, and very different from the
      low prevalence found in South Asia. The morphology of the supernumerary heads
      does not appear to be different from elsewhere in the world based on the minimal
      comparable data available in the literature. The Southeast-East Asian pattern of
      prevalence is consistent with current theories of population history in the
      region and suggests anatomical variation of the postcranial soft tissues may
      ultimately contribute to understanding of past human migrations.

PMID- 27890318
TI  - The mandibular molar pit-tubercle (MMPT) dental nonmetric trait: Comprehensive
      analysis of a large sample.
AB  - Dental nonmetric traits are quasicontinous variables, mostly of genetic origin.
      Thus, sets of such traits allow biological distance estimation between samples.
      Mandibular molar pit-tubercle (MMPT) is a buccal trait defined by Weets (2009) in
      Irish samples. This study aims to analyze (a) trait frequencies, (b) grade
      definitions, (c) intraobserver error, (d) sexual dimorphism, (e) asymmetry, and
      (f) trait associations for MMPT in a Portuguese sample. The first (LM1), second
      (LM2) and third (LM3) lower molars of 600 identified individuals from the Coimbra
      collections were scored for MMPT in three scoring sessions. Intraobserver error,
      bilateral asymmetry and trait correlations were tested using Kendall's tau-b,
      while sexual dimorphism was verified using Pearson's chi2. Frequencies (LM1:
      2.1%; LM2: 3.5%; LM3: 30.3%) were similar to previous reports. However, a new
      free apex cusp form (grade 3+) was detected. Considering three scoring sessions,
      intraobserver precision was above 85%, and correlation coefficients between
      observations were positive and moderate to very strong (0.291<tau-b<0.835).
      Intrasample variation was low, since only LM3 showed sexual dimorphism (female:
      30.2%; males: 16.2%; chi2=15.512; p<0.001; df=1; n=556) and large asymmetry
      (27.1%). There were no strong (tau-b>0.3) intertrait associations involving MMPT.
      MMPT shows low trait presence, sexual dimorphism and asymmetry in stable teeth
      (LM1 and LM2). Intraobserver precision is high, so scoring should be reliable,
      although a plaque and better threshold grade definition is needed. After further
      research on non-European samples, MMPT can be useful in biodistance research.

PMID- 27890319
TI  - Diachronic changes in size and shape of human proximal tibia in Central Europe
      during the latest 1200 years.
AB  - During the past twelve centuries, the stature of Central European inhabitants has
      increased significantly with corresponding changes in the size of lower limb
      bones. The aim of our study was to determine whether these changes have occurred
      strictly in relation to size or if the shape of skeletal structures has been
      altered simultaneously. Diachronic size and shape changes in the proximal part of
      tibia in a Central European population (Czech Republic) were studied using
      geometric morphometrics (principal components analysis, Hotelling's test, linear
      discriminant analysis). The study sample consisted of 183 three-dimensional (3D)
      models of adult tibiae dating to the early Middle Ages (N=65), early 20th century
      (N=60), and from a modern Czech population (N=57). A positive secular trend in
      size manifested only between the two modern Czech populations (the 20th century
      vs. the 21st century), a time range shorter than one century. By contrast,
      landmark-based shape analyses revealed significant differences in tibial
      morphology over the three periods covered in the study. In particular,
      progressive changes were observed in the position of tibial tuberosity (shifted
      medially), the inclination of the line connecting tuberosity with anterior edge
      of the tibial plateau (sloped down), the reshaping of the lower back condyle
      boundary (shifted posteriorly), and reshaping of the medial contour of the medial
      condyle (shifted anteriorly). Changes in the shape of the proximal tibial
      extremity across the chronologically distinct groups indicated the existence of
      discreet but convincing microevolutionary trends involving this anatomical
      structure.

PMID- 27890320
TI  - Trepanation in the Late Bronze Age and Early Iron Age in Armenia.
AB  - In this study, trepanations in ancient Armenia are discussed. In total, 10 cases
      were studied. Seven were male, 1 female and 2 were children. Age of the
      individuals ranged from 6 to 65 years. Among nine cases of surgical trepanations
      four had possible healing signs. In these cases the individuals showed evidence
      of previous trauma to the skull or infection (mastoiditis, tuberculosis),
      suggesting that the operation had been carried out for therapeutic purposes. This
      provides further support for the suggestion that trepanation (or trephination)
      was performed primarily for therapeutic purposes, and because of cranial
      infection or injury. In one case, a symbolic trepanation could imitate real
      penetration into the skull cavity. This study shows that archaeological sites of
      Armenia and anthropological materials have a potential to supply essential
      information on ancient history of the Armenian people and the region.

PMID- 27890321
TI  - Computerized and fingertip measures of reaction time compared in individuals.
AB  - The main purpose of our study was to discover the correlation between the field
      fingertip and computerized methods of measuring reaction time selectively of the
      dominant and non-dominant hands for individual, non-trained, healthy young people
      of senior school age. Forty one, 17 year old, strongly right handed scholars, 21
      boys and 20 girls with body mass indices between 18.5 and 25.0, participated in
      the experiment. The field fingertip method employed a metal metric ruler and the
      computerized method used the Vienna Test System. The point biserial coefficient
      of correlation between these two methods was calculated for each individual. The
      results of demonstrated that the vast majority of participants, 95.2% of males
      and 85.0% of females for the right hand and 95.2% of males and 95.0% of females
      for the left hand had a high level of point biserial coefficient of correlation
      between the two methods. A small number of participants, 3 females and 1 male,
      did not demonstrate a high level of correlation. We speculate that this fact may
      be due to differential expression of muscle fibre types between males and
      females. The portability and ease of use of the field fingertip method are
      advantageous in the field research and provide a reliable measure of reaction
      time. It is important to control the initial gap between the thumb and index
      finger of the person being tested. A metallic metric ruler is adequate
      experimental instrumentation. The mass of the dropped item does not influence the
      measurement.

PMID- 27890322
TI  - "Taking Care of Ourselves": The Experiences of Black Women Approaching and
      Encouraging Male Partners to Test for HIV.
AB  - Sixty percent of young adults living with HIV in the United States are unaware of
      their status despite recommendations to screen everyone. Effective approaches to
      encourage partner testing may increase status awareness. The purpose of our study
      was to understand young Black women's experiences when encouraging a partner to
      test for HIV, preferred approaches, and whether interpersonal context influenced
      the approach. Black women (n = 26) participated in the study in Boston-area focus
      groups (n = 6). Discussions ranged from difficult and stressful to positive and
      empowering. A variety of approaches (expressing caring, seeking understanding,
      leveraging the relationship, ultimatums, subtlety) were described in varied
      interpersonal contexts. Testing and sharing results fostered trust and
      relationship growth. If a partner was resistant, some ended relationships while
      others tested themselves and interpreted their results as their partners' status.
      Our findings could encourage HIV prevention initiatives to consider varied
      interpersonal contexts and enhance partner testing.

PMID- 27890323
TI  - Ventromedial prefrontal cortex generates pre-stimulus theta coherence
      desynchronization: A schema instantiation hypothesis.
AB  - The ventral medial prefrontal cortex (vmPFC) has long been implicated in
      monitoring of memory veracity, and more recently also in memory schema functions.
      In our model of strategic retrieval the two are related. We have proposed that
      the vmPFC has two schema-dependent functions: (i) to establish context-relevant
      templates against which the output of memory systems can be compared; (ii) to
      mediate automatic decision monitoring processes to ensure that only those
      responses that meet the criterion are enacted. Electroencephalogram (EEG) data
      were used to provide evidence that vmPFC supports both functions, and that schema
      instantiation informs monitoring. Participants viewed pictures of acquaintances,
      along with those of famous and nonfamous people, and were asked to respond
      positively only to pictures of individuals they had met (personal familiarity).
      The Self serves as a super-ordinate cognitive schema, facilitating accurate
      endorsement of acquaintances and exclusion of non-personal but familiar faces.
      For the present report we focused on pre-cue tonic oscillatory activity. Controls
      demonstrated theta coherence desynchronization between medial prefrontal areas,
      inferotemporal and lateral temporal cortices. These oscillatory coherence
      patterns were significantly reduced in patients with vmPFC damage, especially in
      those with clinical histories of spontaneous confabulation. Importantly, these
      pre-stimulus cortico-cortical desynchronizations predicted post-cue automatic
      memory activation, as indexed by a familiarity modulation of the face-sensitive
      posterior cortical N170. Pre-cue desynchronization also predicted early post-cue
      frontal positive modulation (P230) and response accuracy. The data are consistent
      with a schema instantiation model that suggests the vmPFC biases posterior
      neocortical long-term memory representations that enhance automatic memory cue
      processing and informs frontally-mediated rapid memory monitoring (P230). Damage
      to these structures can lead to inaccurate, context-irrelevant activation of
      schemas. These, in turn, impair monitoring signals and can lead to confabulation
      when memory control processes are also deficient.

PMID- 27890325
TI  - Functional coupling between frontoparietal and occipitotemporal pathways during
      action and perception.
AB  - Several lines of evidence point to areas in the occipitotemporal pathway as being
      critical in the processes of visual perception and object recognition. Much less
      appreciated, however, is the role that this pathway plays in object-related
      processing for the purposes of visually guided action. Here, using functional MRI
      (fMRI) and functional connectivity (FC) measures, we examined interactions
      between areas in frontoparietal cortex (FPC) involved in grasping, reaching, eye
      movements, and tool use and areas in occipitotemporal cortex (OTC) involved in
      object-, face-, scene-, body-, tool-, and motion-related processing, both during
      the performance of sensorimotor and visual-perceptual tasks, as well as during
      passive fixation (resting-state). Cluster analysis of regional time course data
      identified correspondence in the patterns of FPC and OTC connectivity during the
      visual-perceptual tasks and rest that both tended to segregate regions along
      traditional dorsal/ventral pathway boundaries. During the sensorimotor tasks,
      however, we observed a notable separation in functional coupling between ventral
      medial and ventral-lateral regions of OTC, with several of the latter areas often
      being clustered together with sensorimotor-defined areas in parietal cortex.
      These findings indicate that the functional coupling of ventral-lateral OTC areas
      to dorsal parietal and ventral-medial structures is flexible and task-dependent,
      and suggests that regions in lateral occipital cortex, in particular, may play an
      important role in mediating interactions between the dorsal and ventral pathways
      during tasks involving sensorimotor control.

PMID- 27890324
TI  - Motor skill learning and offline-changes in TGA patients with acute hippocampal
      CA1 lesions.
AB  - Learning and the formation of memory are reflected in various memory systems in
      the human brain such as the hippocampus based declarative memory system and the
      striatum-cortex based system involved in motor sequence learning. It is a matter
      of debate how both memory systems interact in humans during learning and
      consolidation and how this interaction is influenced by sleep. We studied the
      effect of an acute dysfunction of hippocampal CA1 neurons on the acquisition (on
      line condition) and off-line changes of a motor skill in patients with a
      transient global amnesia (TGA). Sixteen patients (68 +/- 4.4 yrs) were studied in
      the acute phase and during follow-up using a declarative and procedural test, and
      were compared to controls. Acute TGA patients displayed profound deficits in all
      declarative memory functions. During the acute amnestic phase, patients were able
      to acquire the motor skill task reflected by increasing finger tapping speed
      across the on-line condition, albeit to a lesser degree than during follow-up or
      compared to controls. Retrieval two days later indicated a greater off-line gain
      in motor speed in patients than controls. Moreover, this gain in motor skill
      performance was negatively correlated to the declarative learning deficit. Our
      results suggest a differential interaction between procedural and declarative
      memory systems during acquisition and consolidation of motor sequences in older
      humans. During acquisition, hippocampal dysfunction attenuates fast learning and
      thus unmasks the slow and rigid learning curve of striatum-based procedural
      learning. The stronger gains in the post-consolidation condition in motor skill
      in CA1 lesioned patients indicate a facilitated consolidation process probably
      occurring during sleep, and suggest a competitive interaction between the memory
      systems. These findings might be a reflection of network reorganization and
      plasticity in older humans and in the presence of CA1 hippocampal pathology.

PMID- 27890326
TI  - The effect of metabolic comorbidities and commonly used drugs on the prognosis of
      patients with ovarian cancer.
AB  - BACKGROUND: Diabetes mellitus is associated with an increased risk of recurrence
      in patients with ovarian cancer. Retrospective studies suggested that the use of
      statins, metformin and beta blockers is associated with improved prognosis in
      these patients. Patients with diabetes often suffer from hypertension and are
      usually treated concomitantly by several classes of drugs. Our aim was to assess
      the independent contribution of diabetes mellitus and hypertension and of the use
      of aspirin, statins, metformin and beta blockers on the risk of ovarian cancer
      recurrence and mortality. METHODS: Files of ovarian cancer patients treated
      between 2000 and 2012 were retrospectively reviewed. Data regarding disease
      characteristics, presence of diabetes mellitus and hypertension, recurrence and
      death were extracted. The use of drugs was assessed using the Clalit Health
      Services (CHS) pharmacy records. RESULTS: 143 patients treated by debulking
      surgery and platinum based chemotherapy were included. Median age was 62.5, 22
      (15.4%) had diabetes mellitus, 61 (42.7%) had chronic hypertension. Statins were
      used by 43 (30%) patients, 31 (21.7%) used aspirin, 25 (17.5%) used beta blockers
      and 12 (8.4%) used metformin. In multivariate analysis diabetes mellitus was
      associated with a shorter recurrence free survival (RFS) and the use of aspirin
      and metformin was associated with a prolonged RFS in this cohort. Overall
      survival (OS) was longer in patients using aspirin and shorter in patients with
      hypertension. CONCLUSIONS: Our data suggests that metabolic comorbidities and
      commonly used drugs are associated with the prognosis of patients with ovarian
      cancer. Additional trials are needed to confirm these observations and test
      therapeutic interventions.

PMID- 27890327
TI  - Hysteroscopic management of life-threatening post-abortion hemorrhage.

PMID- 27890328
TI  - Corrigendum to "Complementary Methods for Contact Hypersensitivity (CHS)
      Evaluation in Mice" [J. Immunol. Methods (2012) 270-275].

PMID- 27890329
TI  - Caroline Buckee - Using Cell Phones to Fight Infectious Disease.

PMID- 27890330
TI  - Assessing surgical residents' imaging interpretation skills.
AB  - PURPOSE: During general surgery (GS) training, residents are expected to
      accurately interpret radiologic images. Objective evidence evaluating residents'
      ability to provide accurate interpretation of imaging studies is currently
      lacking. METHODS: A 30-item web-based test was developed using images from
      different radiologic modalities. Residents from 6 ACGME accredited GS programs
      participated. Residents from 1 radiology program served as a control group.
      RESULTS: 74 GS residents (GSR) enrolled in the online test. The mean score for
      GSR was 75% (+/-9) and 83% (+/-6) for RR (p = 0.006). Residents correctly
      answered 63% x-rays, 74%, CT(head), 84% CT(body), 69% ultrasound, and 88%
      tube/line localization questions. Senior residents were more proficient than
      junior residents at interpreting CT (body) and ultrasound images. CONCLUSION: GS
      residents were able to accurately interpret 75% of basic radiology images. In an
      effort to improve patient care, programs should consider integrating radiological
      education during surgical training.

PMID- 27890331
TI  - The safety of same-day breast reconstructive surgery: An analysis of short-term
      outcomes.
AB  - BACKGROUND: We sought to examine the safety of same-day breast reconstructive
      (BR) surgery. METHODS: An analysis of the American College of Surgeons, National
      Surgical Quality Improvement Program (ACS-NSQIP) files was performed. Patients
      undergoing BR for breast cancer were examined, excluding those with high-risk co
      morbidities or concurrent surgery. A propensity score was calculated and a
      multivariable logistic regression analysis was used to calculate the difference
      in 30-day complications between those undergoing SDS versus longer hospital stay.
      RESULTS: The study consisted of 21,539 patients; 17,449 had implant and 4090 had
      autologous breast reconstruction. 1195 (5.5%) underwent SDS, whereas 20,344
      (94.5%) were admitted at least overnight. On unadjusted analysis, the rate of
      post-operative complications was nearly three times higher in those admitted
      compared to those undergoing SDS (6.7% vs. 2.5%; p < 0.001). On propensity score
      adjusted multivariable regression there was no significant difference in
      complications amongst those undergoing SDS versus staying in hospital (OR 1.4
      (95%CI: 0.9, 2.2)). CONCLUSIONS: These results suggest that admitting BR patients
      does not prevent short-term complications and same day BR surgery is safe when co
      morbidities are accounted for.

PMID- 27890332
TI  - Impact of hospital transfer on surgical outcomes of intestinal atresia.
AB  - BACKGROUND: Examine effects of hospital transfer into a quaternary care center on
      surgical outcomes of intestinal atresia. METHODS: Children <1 yo principally
      diagnosed with intestinal atresia were identified using the Kids' Inpatient
      Database (2012). Exposure variable was patient transfer status. Outcomes measured
      were inpatient mortality, hospital length of stay (LOS) and discharge status.
      Linearized standard errors, design-based F tests, and multivariable logistic
      regression were performed. RESULTS: 1672 weighted discharges represented a
      national cohort. The highest income group and those with private insurance had
      significantly lower odds of transfer (OR:0.53 and 0.74, p < 0.05). Rural patients
      had significantly higher transfer rates (OR: 2.73, p < 0.05). Multivariate
      analysis revealed no difference in mortality (OR:0.71, p = 0.464) or non-home
      discharge (OR: 0.79, p = 0.166), but showed prolonged LOS (OR:1.79, p < 0.05)
      amongst transferred patients. CONCLUSIONS: Significant differences in hospital
      LOS and treatment access reveal a potential healthcare gap. Post-acute care
      resources should be improved for transferred patients.

PMID- 27890333
TI  - Diagnostic evaluation of ovarian torsion: An analysis of pediatric patients using
      the Nationwide Emergency Department Sample.
AB  - BACKGROUND: Ultrasonography (US) is the diagnostic modality of choice during work
      up for ovarian torsion, although computed tomography (CT) may be used. We
      examined the utilization of CT in girls with ovarian torsion, and determined
      which patients are most likely to undergo this study. METHODS: The Nationwide
      Emergency Department Sample dataset was searched for patients <18 years who
      presented with ovarian torsion from 2006 to 2012. Hospitals were categorized by
      the volume of pediatric patients seen. RESULTS: A total of 1279 patients were
      identified. Seven hundred twelve (56%) were seen at adult hospitals, 154 (12%) at
      pediatric privileged, and 413 (32%) at pediatric hospitals. Patients cared for in
      a pediatric or pediatric privileged hospital had more US alone performed to
      diagnose ovarian torsion (p < 0.01). CONCLUSIONS: Girls seen at pediatric
      hospitals are more likely to undergo US for work-up of ovarian torsion.

PMID- 27890334
TI  - Control of carbapenemase-producing Enterobacteriaceae outbreaks in acute
      settings: an evidence review.
AB  - BACKGROUND: In recent years, infections with carbapenemase-producing
      Enterobacteriaceae (CPE) have been increasing globally and present a major public
      health challenge. AIM: To review the international literature: (i) to describe
      CPE outbreaks in acute hospital settings globally; and (ii) to identify the
      control measures used during these outbreaks and report on their effectiveness.
      METHODS: A systematic search of MEDLINE and EMBASE databases, abstract lists for
      key conferences and reference lists of key reviews was undertaken, and
      information on unpublished outbreaks was sought for 2000-2015. Where relevant,
      risk of bias was assessed using the Newcastle-Ottawa scale. A narrative synthesis
      of the evidence was conducted. FINDINGS: Ninety-eight outbreaks were eligible.
      These occurred worldwide, with 53 reports from Europe. The number of cases (CPE
      infection or colonization) involved in outbreaks varied widely, from two to 803.
      In the vast majority of outbreaks, multi-component infection control measures
      were used, commonly including: patient screening; contact precautions (e.g.
      gowns, gloves); handwashing interventions; staff education or monitoring;
      enhanced environmental cleaning/decontamination; cohorting of patients and/or
      staff; and patient isolation. Seven studies were identified as providing the best
      available evidence on the effectiveness of control measures. These demonstrated
      that CPE outbreaks can be controlled successfully using a range of appropriate,
      commonly used, infection control measures. However, risk of bias was considered
      relatively high for these studies. CONCLUSION: The findings indicate that CPE
      outbreaks can be controlled using combinations of existing measures. However, the
      quality of the evidence base is weak and further high-quality research is needed,
      particularly on the effectiveness of individual infection control measures.

PMID- 27890335
TI  - Device-associated infections in a paediatric intensive care unit in Pakistan.
AB  - This study assessed the effect of implementation of active infection control and
      surveillance on the occurrence of device-associated infections (DAIs) in a
      paediatric intensive care unit (PICU) from 2012 to 2015. There were 1378
      patients, equating to 4632 patient-days, on the PICU, and 29 DAI episodes, giving
      an incidence rate of 2.1% and an incidence density rate of 6.26 per 1000 patient
      days. The rates of central-line-associated bloodstream infections, ventilator
      associated pneumonia and catheter-related urinary tract infections were 7/1000
      central-line-days, 1.17/1000 ventilator-days and 0.24/1000 urinary-catheter-days,
      respectively. Despite the overall low rate of DAIs in the PICU, there was a
      relatively high rate of central-line-associated bloodstream infections.

PMID- 27890336
TI  - Complications and revision amputation following trauma-related lower limb loss.
AB  - INTRODUCTION: Trauma-related amputations are a common cause of limb loss in the
      United States. Despite the military and public health impact of trauma-related
      amputations, distributions of various lower limb amputations and the relative
      frequency of complications and revision amputations have not been well described.
      We used the National Trauma Data Bank (NTDB) in order to investigate the
      epidemiology of trauma-related lower extremity amputations among civilians in
      U.S. trauma centers. MATERIALS AND METHODS: We conducted a secondary data
      analysis of the 2011-2012 NTDB research data sets, using means and frequencies to
      characterize the patient population and describe the distribution of major lower
      extremity amputations. Multivariable regression models were fit to identify
      predictors of major post-surgical complications, revision amputation, length of
      hospitalization, and in-hospital mortality. RESULTS: A total of 2879 patients
      underwent a major lower extremity amputation secondary to a trauma-related lower
      limb injury, representing 0.18% of all NTDB trauma admissions from 2011 to 2012.
      80.4% were male and 67.6% were white. The three most frequent definitive
      amputations preformed included trans-tibial (46%), trans-femoral (37.5%), and
      through foot (7.6%). The average length of hospitalization for all amputees was
      22.7days. Patients with at least one revision amputation stayed in the hospital
      approximately 5.5days longer than patients not needing a revision amputation.
      1204 patients (41.8%) required at least one revision amputation. 27.5% of
      amputees experienced at least one major post-surgical complication. African
      Americans experienced a 49% higher major post-surgical complication incidence and
      stayed, on average, 2.5days longer in the hospital compared to whites. Injury
      severity score, age, hospital teaching status, presence of a crush injury,
      fracture location, presence of compartment syndrome, and experiencing a major
      post-surgical complication were all significant predictors of revision
      amputation. CONCLUSION: We report a high rate of complications and revision
      amputations among trauma-related lower limb amputees, and identify predictors of
      surgical outcomes that have not been described in the literature including
      African American race. Compartment syndrome is a significant predictor of major
      post-surgical complications, revision amputation, and length of hospitalization.

PMID- 27890337
TI  - A double button adjustable loop device is biomechanically equivalent to tension
      band wire in the fixation of transverse patellar fractures-A cadaveric study.
AB  - INTRODUCTION: Tension-band wire fixation of patellar fractures is associated with
      significant hardware-related complications and infection. Braided polyester
      suture fixation is an alternative option. However, these suture fixations have
      higher failure rates due to the difficulty in achieving rigid suture knot
      fixation. The Arthrex syndesmotic TightRope, which is a double-button adjustable
      loop fixation device utilizing a 4-point locking system using FibreWire, may not
      only offer stiff rigid fixation using a knotless system, but may also obviate the
      need for implant removal due to hardware related problems. The aim of our study
      is to compare the fixation rigidity of patella fractures using Tightrope versus
      conventional tension-band wiring (TBW) in a cadaveric model. MATERIALS AND
      METHODS: TBW fixation was compared to TightRope fixation of transverse patella
      fractures in 5 matched pairs of cadaveric knees. The knees were cyclically
      brought through 0-90 degrees  of motion for a total of 500 cycles. Fracture
      gapping was measured before the start of the cycling, and at 50, 100, 200 and 500
      cycles using an extensometer. The mean maximum fracture gapping was derived.
      Failure of the construct was defined as a displacement of more than 3mm, patella
      fracture or implant breakage. RESULTS: All but one knee from each group survived
      500 cycles. The two failures were due to a fracture gap of more than 3mm during
      cycling. There was no significant difference in the mean number of cycles
      tolerated. There was no implant breakage. There was no statistical significant
      difference in mean maximum fracture gap between the TBW and TightRope group at
      all cyclical milestones after 500 cycles (0.3026+/-0.4091mm vs 0.3558+/-0.7173mm,
      p=0.388). CONCLUSIONS: We found no difference between the TBW and Tightrope
      fixation in terms of fracture gapping and failure. With possible lower risk of
      complications such as implant migration and soft tissue irritation, we believe
      tightrope fixation is a feasible alternative in fracture management of transverse
      patella fractures.

PMID- 27890338
TI  - A longitudinal study on transmission of Staphylococcus aureus genotype B in Swiss
      communal dairy herds.
AB  - Staphylococcus aureus is a common mastitis causing pathogen of dairy cattle.
      Several S. aureus genotypes exist, of which genotype B (GTB) is highly prevalent
      in Swiss dairy herds. Dairy farming in mountainous regions of Switzerland is
      characterised by the movement of dairy cattle to communal pasture-based
      operations at higher altitudes. Cows from different herds of origin share
      pastures and milking equipment for a period of 2 to 3 months during summer. The
      aim of this longitudinal observational study was to quantify transmission of S.
      aureus GTB in communal dairy operations. Cows (n=551) belonging to 7 communal
      operations were sampled at the beginning and end of the communal period.
      Transmission parameter beta was estimated using a Susceptible-Infectious
      Susceptible (SIS) model. The basic reproduction ratio R0 was subsequently derived
      using previously published information about the duration of infection. Mean
      transmission parameter beta was estimated to be 0.0232 (95% CI: 0.0197-0.0274).
      R0 was 2.6 (95% CI: 2.2-3.0), indicating that S. aureus GTB is capable of causing
      major outbreaks in Swiss communal dairy operations. This study emphasized the
      contagious behaviour of S. aureus GTB. Mastitis management in communal dairy
      operations should be optimized to reduce S. aureus GTB transmission between cows
      and back to their herds of origin.

PMID- 27890340
TI  - Ischemia evaluation in patients with myocardial bridging: It's a tough situation?

PMID- 27890339
TI  - Spontaneous coronary artery dissection undissolved using cardiac computed
      tomography: Response and a question.

PMID- 27890341
TI  - Reply to "particulars of diabetes mellitus may matter in patients with Takotsubo
      Syndrome".

PMID- 27890342
TI  - Impact of laparoscopic Roux-en-Y Gastric bypass versus sleeve gastrectomy on
      postoperative lipid values.
AB  - BACKGROUND: Metabolic surgery has been shown to significantly improve many
      obesity-related co-morbidities, including dyslipidemia. The literature has
      produced mixed results comparing postoperative lipid values after laparoscopic
      Roux-en-Y gastric bypass (LRYGB) compared to laparoscopic sleeve gastrectomy
      (LSG); with some indicating significantly greater reductions in total cholesterol
      and low-density lipoprotein (LDL) in LRYGB versus LSG, and others reporting no
      significant differences. OBJECTIVES: To evaluate the postoperative lipid values
      after LRYGB versus LSG at a community hospital. SETTING: Integrated
      multispecialty health system with a community teaching hospital. METHODS: A
      retrospective review of our prospective database was completed to identify
      patients who underwent either LRYGB or LSG at our institution from 2001 through
      2013. Lipid values available at 6-18 months postoperative were evaluated.
      Statistical analysis included chi2 and Wilcoxon rank-sum tests. A P value<.05 was
      considered significant. RESULTS: There were 1326 and 121 patients who underwent
      LRYGB and LSG during the study period, respectively. Of these patients, 644 LRYGB
      and 67 LSG patients had pre- and postoperative lipid values available and
      included in the final analysis. Postoperative mean total cholesterol and LDL
      values were significantly lower in LYRGB versus LSG patients. Postoperatively,
      10% and 30% of LRYGB and LSG patients had a total cholesterol values>=200 mg/dL
      (P<.001); 4% and 24% had LDL values>=130 mg/dL (P<.001); and 8% and 9% had
      triglyceride levels>130 mg/dL (P = .68), respectively. HDL values were within the
      recommended range in 52% and 57% of LRYGB and LSG patients, respectively (P =
      .64). CONCLUSION: Patients who underwent LRYGB had a greater postoperative
      reduction in total cholesterol, LDL, and triglycerides. LRYGB may be the more
      appropriate bariatric procedure for patients with significant preoperative
      hypercholesterolemia.

PMID- 27890343
TI  - Innovative Metabolic Operations.

PMID- 27890344
TI  - Community-level moderators of a school-based childhood sexual assault prevention
      program.
AB  - Childhood sexual abuse (CSA) is highly prevalent and associated with a wide
      variety of negative mental and physical health outcomes. School-based CSA
      education and prevention programs have shown promise, but it is unclear to what
      extent community-level characteristics are related to their effectiveness. The
      present cluster randomized controlled trial evaluated community-level moderators
      of the Safe@Lastprogramcomparedtoawaitlistcontrolcondition.(*) Knowledge gains
      from pre- to post-intervention were assessed in 5 domains: safe versus unsafe
      people; safe choices; problem-solving; clear disclosure; and assertiveness.
      Participants were 1177 students (46% White, 26% African American, 15% Hispanic,
      4% Asian American, 6% Other) in grades 1 through 6 from 14 public schools in
      Tennessee. Multilevel models accounting for the nesting of children within
      schools revealed large effect sizes for the intervention versus control across
      all knowledge domains (d's ranged from 1.56 to 2.13). The effectiveness of the
      program was moderated by mean per capita income and rates of substantiated cases
      of child abuse and neglect in the community. Intervention effects were stronger
      for youth living in lower as compared to higher income counties, and for youth
      attending schools in counties with lower as compared to higher abuse/neglect
      rates. Child characteristics (sex, race) did not moderate intervention effects.
      This research identified two community-level factors that predicted the
      effectiveness of a CSA education and prevention program designed to improve
      children's knowledge of personal safety skills. School-based CSA prevention
      programs may require modification for communities with higher rates of child
      abuse and neglect.

PMID- 27890345
TI  - Prenatal exposure to outdoor air pollution and child behavioral problems at
      school age in Japan.
AB  - INTRODUCTION: Recent studies suggest positive associations between prenatal
      exposure to ambient air pollution and neurodevelopment of children, but evidence
      on the adverse effects of exposure to air pollution on child neurobehavioral
      development remains limited. We thus examined associations between prenatal
      exposure to outdoor air pollution and child behavioral problems at school age,
      using data from a nationwide population-based longitudinal survey in Japan, where
      participants were recruited in 2001 and are continuously followed. METHODS:
      Suspended particulate matter (SPM), nitrogen dioxide, and sulfur dioxide
      concentrations during the 9months before birth were obtained at municipality
      level and assigned to those participants born in the corresponding municipality.
      We analyzed data from singleton births with linked pollution data available
      (e.g., n=33,911 for SPM). We used responses to survey questions about behavioral
      problems at age 8years. We conducted multilevel logistic regression analysis,
      adjusting for individual and municipality-level variables. RESULTS: Air pollution
      exposure during gestation was positively associated with risk for behavioral
      problems related to attention and delinquent or aggressive behavior. In the fully
      adjusted models, odds ratios following a one-interquartile-range increase in SPM
      were 1.06 (95% confidence interval: 1.01, 1.11) for interrupting others, 1.09
      (1.03, 1.15) for failure to pay attention when crossing a street, 1.06 (1.01,
      1.11) for lying, and 1.07 (1.02, 1.13) for causing public disturbance.
      CONCLUSIONS: Prenatal exposure to outdoor air pollution was associated with
      behavioral problems related to attention and delinquent or aggressive behavior at
      age 8years in a nationally representative sample in Japan.

PMID- 27890346
TI  - The UK HeartSpare Study (Stage II): Multicentre Evaluation of a Voluntary Breath
      hold Technique in Patients Receiving Breast Radiotherapy.
AB  - AIMS: To evaluate the feasibility and heart-sparing ability of the voluntary
      breath-hold (VBH) technique in a multicentre setting. MATERIALS AND METHODS:
      Patients were recruited from 10 UK centres. Following surgery for early left
      breast cancer, patients with any heart inside the 50% isodose from a standard
      free-breathing tangential field treatment plan underwent a second planning
      computed tomography (CT) scan using the VBH technique. A separate treatment plan
      was prepared on the VBH CT scan and used for treatment. The mean heart, left
      anterior descending coronary artery (LAD) and lung doses were calculated. Daily
      electronic portal imaging (EPI) was carried out and scanning/treatment times were
      recorded. The primary end point was the percentage of patients achieving a
      reduction in mean heart dose with VBH. Population systematic (Sigma) and random
      errors (sigma) were estimated. Within-patient comparisons between techniques used
      Wilcoxon signed-rank tests. RESULTS: In total, 101 patients were recruited during
      2014. Primary end point data were available for 93 patients, 88 (95%) of whom
      achieved a reduction in mean heart dose with VBH. Mean cardiac doses (Gy) for
      free-breathing and VBH techniques, respectively, were: heart 1.8 and 1.1, LAD
      12.1 and 5.4, maximum LAD 35.4 and 24.1 (all P<0.001). Population EPI-based
      displacement data showed Sigma =+1.3-1.9 mm and sigma=1.4-1.8 mm. Median CT and
      treatment session times were 21 and 22 min, respectively. CONCLUSIONS: The VBH
      technique is confirmed as effective in sparing heart tissue and is feasible in a
      multicentre setting.

PMID- 27890347
TI  - Isolated limb perfusion for the management limb threatening soft tissue sarcomas:
      The role of histological type on clinical outcomes.
AB  - BACKGROUND: Hyperthermic isolated limb perfusion (HILP) is an effective
      neoadjuvant treatment to avoid amputation in patients with locally advanced
      extremity soft tissue sarcomas (STS). We aimed to investigate whether STS
      histological type plays a role in predicting clinical outcomes. METHODS: This
      study reports a retrospective analysis of 125 patients with limb threatening STS
      (liposarcoma, n = 41; malignant peripheral nerve sheath tumor, n = 20;
      leiomyosarcoma, n = 20; miscellany, n = 44), who underwent HILP from 1990 through
      2015 at our institution. The following endpoints were evaluated: tumor response
      (assessed by radiological imaging and histology), limb sparing rate, local
      progression-free survival (LPFS) and overall survival (OS). RESULTS: On average,
      overall (complete + partial) tumor response was significantly greater in patients
      affected with liposarcoma as compared to those with other histotypes
      (radiological response rate: 38/41, 92.7% vs 66/84, 78.6%, P-value: 0.048; mean
      histological necrosis: 83.6% vs 52.9%, P < 0.0001). Limb sparing rate was also
      higher among patients with liposarcoma as compared to other histotypes (39/41,
      95.1% vs 62/84, 73.8%, P-value: 0.005). As regards survival, LPFS was similar
      across tumor types, whereas OS resulted significantly worse in patients with limb
      leiomyosarcoma (log-rank P-value: 0.009). CONCLUSIONS: HILP is a very effective
      treatment modality for limb threatening STS. In our series, liposarcoma appears
      to be the histological type most sensitive to HILP in terms of tumor response and
      thus limb sparing, which might help clinicians in the patient selection process.

PMID- 27890348
TI  - Out-of-the-box pelvic surgery including iliopsoas resection for recurrent
      gynecological malignancies: Does that make sense? A single-institution case
      series.
AB  - OBJECTIVE: To report morbidity and oncological outcomes in a consecutive series
      of lateral isolated recurrent gynecological cancer involving the pelvic side wall
      (PSW) including the iliopsoas muscle. MATERIAL AND METHODS: We retrospectively
      evaluated a consecutive series between 6/2013 and 12/2015 of lateral isolated
      recurrent gynecological malignancies treated with a lateral endopelvic resection
      (LEPR). LEPR was defined as an en-bloc lateral resection of a pelvic tumor with
      sidewall muscle, and/or bone, and/or major nerve, and/or major vascular
      structure. Post-surgical complications, quality of life (QoL) and survivals were
      computed. RESULTS: Seventy-four women with pelvic isolated relapse were admitted
      for surgery during the study period. Among them, 8 cases (10.8%) showed lateral
      isolated relapse involving the iliopsoas muscle and were treated with LEPR. R0
      resection was achieved in 6/8 patients (75.0%), while the pathologic margins were
      microscopically and macroscopically positive in 1 patient (12.5%), respectively.
      There were no perioperative mortalities. Major postoperative complications
      occurred in 3 patients (37.5%) through peripheral neuropathies, thrombosis of the
      vascular graft and compartment syndrome of the leg. Median follow-up time was 21
      months (range, 12-28). The 2-year overall survival (OS) was 88% improving up to
      100% if R0 resection was achieved. In patients with positive pathologic margins
      (n = 2), the 2-year OS was 50%. All women showed an improved QoL after surgery.
      CONCLUSION: LEPR with iliopsoas resection can be safely performed in selected
      cases with lateral isolated gynecological relapse involving the PSW and was
      associated with improved QoL and prolonged survival when an R0 resection was
      achieved.

PMID- 27890349
TI  - Clinical features and outcomes of 20 patients with abdominopelvic desmoplastic
      small round cell tumor.
AB  - INTRODUCTION: Desmoplastic small round cell tumor (DSRCT) is a rare mesenchymal
      malignancy. We describe our experience with treating DSRCT at a large sarcoma
      referral center. METHODS: A retrospective chart review was performed on DSRCT
      patients referred to our institution (1998-2014). Pathology specimens were
      reviewed to confirm the diagnosis. Clinical and imaging were extracted and
      summarized with descriptive statistics. Univariate analysis was performed to
      evaluate the association between patient, tumor, and treatment variables and
      overall survival (OS). RESULTS: In this study cohort of 20 patients, median age
      at presentation was 29 y (range 18-43) and 90% were male. Fifty-five percent
      presented with metastasis. Patients underwent chemotherapy (n = 20), radiation
      therapy (n = 3), and cytoreductive surgery (CRS) (n = 5). Median OS was 22 m
      (interquartile range: 12-28 m). Five-year OS rate was 20%. Extra-abdominal
      metastasis was associated with a higher hazard ratio (HR) of mortality (HR: 3.1,
      95% C.I. 1.0-9.4, p = 0.04), while CRS improved OS (HR: 0.1, 95% C.I. 0.03-0.7, p
      = 0.02). CONCLUSIONS: Despite aggressive treatment, less than half of the
      patients were dead of DSRCT within 2 years of presentation. Although a select
      group of patients who underwent CRS had improved OS, novel treatments are
      urgently needed.

PMID- 27890350
TI  - The histophysiology and pathophysiology of the peritoneum.
AB  - The peritoneum is an extensive serous organ with both epithelial and mesenchymal
      features and a variety of functions. Diseases such as inflammatory peritonitis
      and peritoneal carcinomatosis can induce disturbance of the complex physiological
      functions. To understand the peritoneal response in disease, normal embryonic
      development, anatomy in healthy conditions and physiology of the peritoneum have
      to be understood. This review aims to summarize and discuss the literature on
      these basic peritoneal characteristics. The peritoneum is a dynamic organ capable
      of adapting its structure and functions to various physiological and pathological
      conditions. It is a key element in regulation of inflammatory responses, exchange
      of peritoneal fluid and prevention of fibrosis in the abdominal cavity.
      Disturbance of these mechanisms may lead to serious conditions such as the
      production of large amounts of ascites, the generation of fibrotic adhesions,
      inflammatory peritonitis and peritoneal carcinomatosis. The difficulty to treat
      diseases, such as inflammatory peritonitis and peritoneal carcinomatosis,
      stresses the necessity for new therapeutic strategies. This review provides a
      detailed background on the peritoneal anatomy, microenvironment and immunologic
      responses which is essential to generate new hypotheses for future research.

PMID- 27890351
TI  - Unilaminar follicular cells transiently express galectin-3 during ovarian
      folliculogenesis in pigs.
AB  - The localization of galectin-3, a beta-galactoside-binding animal lectin, was
      immunohistochemically studied in the ovaries of pigs to determine its expression
      in ovarian folliculogenesis. Various stages of ovarian follicles were identified
      in the ovaries of adult pigs. Galectin-3 was immunostained in the squamous
      follicular cells surrounding oocytes in primordial follicles and in the
      unilaminar granulosa cells of primary follicles, but not in oocytes of
      multilaminar follicles (including primary, secondary, and tertiary Graafian
      follicles). As in adult ovaries, galectin-3 immunoreactivity was prominent in the
      unilaminar follicles in neonatal ovaries. Galectin-3 was also immunolocalized in
      the luteal cells in the corpus luteum and granulosa cells of atretic follicles as
      well as in interstitial macrophages in porcine ovaries. Collectively, these
      results suggest that galectin-3 is transiently expressed in follicular cells in
      the unilaminar ovarian follicles (primordial and primary) but not in multilaminar
      ovarian follicles (primary to tertiary), implying that galectin-3 is
      embryologically involved in ovum generation.

PMID- 27890352
TI  - Residential Aged Care Medication Review to Improve the Quality of Medication Use:
      A Systematic Review.
AB  - BACKGROUND: Aging is often associated with various underlying comorbidities that
      warrant the use of multiple medications. Various interventions, including
      medication reviews, to optimize pharmacotherapy in older people residing in aged
      care facilities have been described and evaluated. Previous systematic reviews
      support the positive impact of various medication-related interventions but are
      not conclusive because of several factors. OBJECTIVES: The current study aimed to
      assess the impact of medication reviews in aged care facilities, with additional
      focus on the types of medication reviews, using randomized controlled trials
      (RCTs) and observational studies. METHODS: A systematic searching of English
      articles that examined the medication reviews conducted in aged care facilities
      was performed using the following databases: PubMed, CINAHL, IPA, TRiP, and the
      Cochrane Library, with the last update in December 2015. Extraction of articles
      and quality assessment of included articles were performed independently by 2
      authors. Data on interventions and outcomes were extracted from the included
      studies. The SIGN checklist for observational studies and the Cochrane
      Collaboration's tool for assessing risk of bias in RCTs were applied. Outcomes
      assessed were related to medications, reviews, and adverse events. RESULTS:
      Because of the heterogeneity of the measurements, it was deemed inappropriate to
      conduct a meta-analysis and thus a narrative approach was employed. Twenty-two
      studies (10 observational studies and 12 controlled trials) were included from
      1141 evaluated references. Of the 12 trials, 8 studies reported findings of
      pharmacist-led medication reviews and 4 reported findings of multidisciplinary
      team-based reviews. The medication reviews performed in the included trials were
      prescription reviews (n = 8) and clinical medication reviews (n = 4). In the case
      of the observational studies, the majority of the studies (8/12 studies) reported
      findings of pharmacist-led medication reviews, and only 2 studies reported
      findings of multidisciplinary team-based reviews. Similarly, 6 studies employed
      prescription reviews, whereas 4 studies employed clinical medication reviews. The
      majority of the recommendations put forward by the pharmacist or a
      multidisciplinary team were accepted by physicians. The number of prescribed
      medications, inappropriate medications, and adverse outcomes (eg, number of
      deaths, frequency of hospitalizations) were reduced in the intervention group.
      CONCLUSION: Medication reviews conducted by pharmacists, either working
      independently or with other health care professionals, appear to improve the
      quality of medication use in aged care settings. However, robust conclusions
      cannot be drawn because of significant heterogeneity in measurements and
      potential risk for biases.

PMID- 27890354
TI  - Chairside CAD/CAM materials. Part 1: Measurement of elastic constants and
      microstructural characterization.
AB  - OBJECTIVE: A deeper understanding of the mechanical behavior of dental
      restorative materials requires an insight into the materials elastic constants
      and microstructure. Here we aim to use complementary methodologies to thoroughly
      characterize chairside CAD/CAM materials and discuss the benefits and limitations
      of different analytical strategies. METHODS: Eight commercial CAM/CAM materials,
      ranging from polycrystalline zirconia (e.max ZirCAD, Ivoclar-Vivadent),
      reinforced glasses (Vitablocs Mark II, VITA; Empress CAD, Ivoclar-Vivadent) and
      glass-ceramics (e.max CAD, Ivoclar-Vivadent; Suprinity, VITA; Celtra Duo,
      Dentsply) to hybrid materials (Enamic, VITA; Lava Ultimate, 3M ESPE) have been
      selected. Elastic constants were evaluated using three methods: Resonant
      Ultrasound Spectroscopy (RUS), Resonant Beam Technique (RBT) and Ultrasonic Pulse
      Echo (PE). The microstructures were characterized using Scanning Electron
      Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDX), Raman Spectroscopy
      and X-ray Diffraction (XRD). RESULTS: Young's modulus (E), Shear modulus (G),
      Bulk modulus (B) and Poisson's ratio (nu) were obtained for each material. E and
      nu reached values ranging from 10.9 (Lava Ultimate) to 201.4 (e.max ZirCAD) and
      0.173 (Empress CAD) to 0.47 (Lava Ultimate), respectively. RUS showed to be the
      most complex and reliable method, while the PE method the easiest to perform but
      most unreliable. All dynamic methods have shown limitations in measuring the
      elastic constants of materials showing high damping behavior (hybrid materials).
      SEM images, Raman spectra and XRD patterns were made available for each material,
      showing to be complementary tools in the characterization of their crystal
      phases. SIGNIFICANCE: Here different methodologies are compared for the
      measurement of elastic constants and microstructural characterization of CAD/CAM
      restorative materials. The elastic properties and crystal phases of eight
      materials are herein fully characterized.

PMID- 27890355
TI  - The effects of cavity-margin-angles and bolus stiffness on the mechanical
      behavior of indirect resin composite class II restorations.
AB  - OBJECTIVE: To study the influence of the different class II mesio-occlusal-distal
      (MOD) cavity shape on the stress and strain distributions in adhesive indirect
      restorations, using numerical finite element analysis (FEA). To investigate the
      relationship between restored teeth failure and stiffness of food, three values
      of Young's modulus were used for the food. METHODS: A 3D model of a sound lower
      molar and three class II MOD cavities with different shape were created. Slide
      type contact elements were used between tooth surface and food. An adhesive resin
      based cement, modeled with fixed-type contact elements, and a single restorative
      filling materials were considered. To simulate polymerization shrinkage effect,
      which is basically restricted to the thin composite cement layer, shell elements
      were employed and the thermal expansion approach was used. A vertical occlusal
      load of 600N was applied, while assigning fixed zero-displacements on the cutting
      surfaces below the crevices. All the materials were assumed to be isotropic and
      elastic. A static linear analysis was carried out. RESULTS: In the lingual cusp,
      the displacements increased as the values of the stiffness food increased. In the
      restored teeth, the stress near the restoration-tooth interface was strongly
      dependent on the MOD cavity shape. The stress peaks were mainly located along the
      enamel-dentin interface at the lingual side; wedge-shaped MOD cavity with a low
      angle, in combination with the lowest food stiffness provided the best results.
      SIGNIFICANCE: A more complex load application on the occlusal surfaces was
      introduced. Food stiffness slightly affected the stress distribution of the
      restored and sound teeth. Teeth with adhesive class II MOD indirect resin
      composite restorations were potentially more susceptible to damage if the class
      II MOD cavity-margin-angle was higher than 95 degrees . Restored teeth with a
      higher cavity-margin-angle led to considerable stress concentration in the
      lingual cusp along the enamel-dentin interface. These models were more
      susceptible to fracture in the lingual cusps when compared to the buccal ones.

PMID- 27890353
TI  - Anxiety and Nicotine Dependence: Emerging Role of the Habenulo-Interpeduncular
      Axis.
AB  - While innovative modern neuroscience approaches have aided in discerning brain
      circuitry underlying negative emotional behaviors including fear and anxiety
      responses, how these circuits are recruited in normal and pathological conditions
      remains poorly understood. Recently, genetic tools that selectively manipulate
      single neuronal populations have uncovered an understudied circuit, the medial
      habenula (mHb)-interpeduncular (IPN) axis, that modulates basal negative
      emotional responses. Interestingly, the mHb-IPN pathway also represents an
      essential circuit that signals heightened anxiety induced by nicotine withdrawal.
      Insights into how this circuit interconnects with regions more classically
      associated with anxiety, and how chronic nicotine exposure induces
      neuroadaptations resulting in an anxiogenic state, may thereby provide novel
      strategies and molecular targets for therapies that facilitate smoking cessation,
      as well as for anxiety relief.

PMID- 27890356
TI  - Does 8-methacryloxyoctyl trimethoxy silane (8-MOTS) improve initial bond strength
      on lithium disilicate glass ceramic?
AB  - OBJECTIVES: Dental ceramic surfaces are modified with silane coupling agents,
      such as gamma-methacryloxypropyl trimethoxy silane (gamma-MPTS), to improve bond
      strength. For bonding between lithium disilicate glass ceramic and resin cement,
      the objective was to investigate if 8-methacryloxyoctyl trimethoxy silane (8
      MOTS) could yield a similar performance as the widely used gamma-MPTS. METHODS:
      One hundred and ten lithium disilicate glass ceramic specimens were randomly
      divided into 11 groups (n=10) according to pretreatment regime. All specimens
      were pretreated with a different solution composed of one or a combination of
      these agents: 10 or 20wt% silane coupling agent of gamma-MPTS or 8-MOTS, followed
      by a hydrolysis solution of acetic acid or 10-methacryloyloxydecyl dihydrogen
      phosphate (10-MDP). Each pretreated surface was luted to a stainless steel rod of
      3.6mm diameter and 2.0mm height with resin cement. Shear bond strength between
      ceramic and cement was measured after 24-h storage in 37 degrees C distilled
      water. RESULTS: 8-MOTS produced the same bonding performance as gamma-MPTS. Both
      silane coupling agents significantly increased the bond strength of resin cement,
      depending on their concentration. When activated by 10-MDP hydrolysis solution,
      20wt% concentration produced the highest values (gamma-MPTS: 24.9+/-5.1MPa; 8
      MOTS: 24.6+/-7.4MPa). Hydrolysis with acetic acid produced lower bond strengths
      than with 10-MDP. SIGNIFICANCE: Silane coupling pretreatment with 8-MOTS
      increased the initial bond strength between lithium disilicate glass ceramic and
      resin cement, rendering the same bonding effect as the conventional gamma-MPTS.

PMID- 27890357
TI  - Effect of cement space on stress distribution in Y-TZP based crowns.
AB  - OBJECTIVE: To evaluate the stress distribution in bi-layered Y-TZP based crowns,
      according to the occlusal internal spacing between coping and abutment. METHODS:
      Twelve premolar shaped Y-TZP copings were made by a CAD/CAM system and seated on
      an abutment to evaluate the internal fit at the occlusal third using micro-CT
      images. Considering the fitting range obtained experimentally, two 3D finite
      element models, consisting on bone tissue, a titanium implant, a zirconia
      abutment, cement layer and a bi-layered Y-TZP ceramic crown were constructed
      based on the micro-CT images, one corresponding to the thinnest cement space and
      other representing the specimen with the thickest cement space obtained
      experimentally. A 250N axial load was applied at the center of the occlusal
      surface of the crown (?0,8mm2 area) and the first principal stress distribution
      was plotted and analyzed. RESULTS: The greatest maximum principal stress occurred
      within the veneer ceramic right below the site of loading. The thickest cement
      model showed higher stress concentration at the center of occlusal surface of
      veneer and the center of occlusal internal surface of coping. SIGNIFICANCE:
      Knowledge of stress distribution in ceramic crowns with different cement
      thicknesses will help clinicians to properly adjust crown fit, in seeking to
      avoid porcelain fractures.

PMID- 27890359
TI  - Selective removal of cesium by ammonium molybdophosphate - polyacrylonitrile bead
      and membrane.
AB  - The selective removal of radionuclides with extremely low concentrations from
      environmental medium remains a big challenge. Ammonium molybdophosphate possess
      considerable selectivity towards cesium ion (Cs+) due to the specific ion
      exchange between Cs+ and NH4+. Ammonium molybdophosphate - polyacrylonitrile (AMP
      PAN) membrane was successfully prepared for the first time in this study.
      Efficient removal of Cs+ (95.7%, 94.1% and 91.3% of 1mgL-1) from solutions with
      high ionic strength (400mgL-1 of Na+, Ca2+ or K+) was achieved by AMP-PAN
      composite. Multilayer chemical adsorption process was testified through kinetic
      and isotherm studies. The estimated maximum adsorption capacities even reached
      138.9+/-21.3mgg-1. Specifically, the liquid film diffusion was identified as the
      rate-limiting step throughout the removal process. Finally, AMP-PAN membrane
      could eliminate Cs+ from water effectively through the filtration adsorption
      process.

PMID- 27890358
TI  - Nucleo-mitochondrial interaction of yeast in response to cadmium sulfide quantum
      dot exposure.
AB  - Cell sensitivity to quantum dots (QDs) has been attributed to a cascade triggered
      by oxidative stress leading to apoptosis. The role and function of mitochondria
      in animal cells are well understood but little information is available on the
      complex genetic networks that regulate nucleo-mitochondrial interaction. The
      effect of CdS QD exposure in yeast Saccharomyces cerevisiae was assessed under
      conditions of limited lethality (<10%), using cell physiological and
      morphological endpoints. Whole-genomic array analysis and the screening of a
      deletion mutant library were also carried out. The results showed that QDs:
      increased the level of reactive oxygen species (ROS) and decreased the level of
      reduced vs oxidized glutathione (GSH/GSSG); reduced oxygen consumption and the
      abundance of respiratory cytochromes; disrupted mitochondrial membrane potentials
      and affected mitochondrial morphology. Exposure affected the capacity of cells to
      grow on galactose, which requires nucleo-mitochondrial involvement. However, QDs
      exposure did not materially induce respiratory deficient (RD) mutants but only RD
      phenocopies. All of these cellular changes were correlated with several key
      nuclear genes, including TOM5 and FKS1, involved in the maintenance of
      mitochondrial organization and function. The consequences of these cellular
      effects are discussed in terms of dysregulation of cell function in response to
      these "pathological mitochondria".

PMID- 27890360
TI  - Anti-tubercular peptides: A quest of future therapeutic weapon to combat
      tuberculosis.
AB  - Tuberculosis (TB) is a symbolic menace to mankind, infecting almost one third of
      the world's populace and causing over a million mortalities annually.
      Mycobacterium tuberculosis (Mtb) is the key pathogen of TB that invades and
      replicates inside the host's macrophage. With the emerging dilemma of multi-drug
      resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR
      TB), the exigency for developing new TB drugs is an obligation now for worldwide
      researchers. Among the propitious antimycobacterial agents examined in last few
      decades, anti-tubercular peptides have been substantiated to be persuasive with
      multiple advantages such as low immunogenicity, selective affinity to bacterial
      negatively charged cell envelopes and most importantly divergent mechanisms of
      action. In this review, we epitomized the current advances in the anti-tubercular
      peptides, focusing the sources and highlighting the mycobactericidal mechanisms
      of promising peptides. The review investigates the current anti-tubercular
      peptides exploited not only from human immune cells, human non-immune cells,
      bacteria and fungi but also from venoms, cyanobacteria, bacteriophages and
      several other unplumbed sources. The anti-tubercular peptides of those origins
      are also known to have unique second non-membrane targets within Mtb. The present
      context also describes the several cases that manifested the severe side effects
      of extant anti-TB drugs. The downfall, failure to reach clinical trial phases,
      inept to MDR- or XDR-TB and severe complications of the currently available anti
      tubercular drugs accentuate the imperative necessity to develop efficacious drugs
      from adequate anti-tubercular peptides. Keeping in view of the emerging trends of
      drug resistant Mtb globally and unexampled mycobactericidal characteristics of
      peptides, the anti-tubercular peptides of varied origins can be used as a
      potential weapon to eradicate TB in future by developing new therapeutic drugs.

PMID- 27890361
TI  - Iron dysregulation in beta-thalassemia.
AB  - Iron deficiency anemia and iron overload conditions affect more than one billion
      people worldwide. Iron homeostasis involves the regulation of cells that export
      iron into the plasma and cells that utilize or store iron. The cellular iron
      balance in humans is primarily mediated by the hepcidin-ferroportin axis.
      Ferroportin is the sole cellular iron export protein, and its expression is
      regulated transcriptionally, post-transcriptionally and post-translationally.
      Hepcidin, a hormone produced by liver cells, post-translationally regulates
      ferroportin expression on iron exporting cells by binding with ferroportin and
      promoting its internalization by endocytosis and subsequent degradation by
      lysosomes. Dysregulation of iron homeostasis leading to iron deposition in vital
      organs is the main cause of death in beta-thalassemia patients. Beta-thalassemia
      patients show marked hepcidin suppression, ineffective erythropoiesis, anemia and
      iron overload. Beta-thalassemia is common in the Mediterranean region, Southeast
      Asia and the Indian subcontinent, and the focus of this review is to provide an
      update on the factors mediating hepcidin related iron dysregulation in beta
      thalassemia disease. Understanding this process may pave the way for new
      treatments to ameliorate iron overloading and improve the long term prognosis of
      these patients.

PMID- 27890362
TI  - Epidemiology of polio virus infection in Pakistan and possible risk factors for
      its transmission.
AB  - End Polio Pakistan program still has to overcome many hurdles; unfortunately on
      8th February 2016 first polio case of the year has surfaced in Karachi. It seems
      that battle against polio demands little bit more conviction and motivation. WHO
      has set a goal of polio eradication in Pakistan till 2018, in order to evaluate
      the success of this target; polio eradication campaign in Pakistan has been
      analyzed in different perspectives. Our analysis indicated that major obstacles
      in eradication are low literacy rate, poor health infrastructure, lack of
      planning, natural disaster, economic crisis, counter insurgencies and almost no
      protection for polio health workers. WHO has allocated new funds to tackle this
      problem, now there is a need to spend this money more effectively; with proper
      planning and honest deployment of funds.

PMID- 27890363
TI  - Comparative genome analysis between Southeast Asian and South American Zika
      viruses.
AB  - OBJECTIVE: To understand the cause for the differences between potentially mild
      Southeast Asian and the more pathogenic ZIKV in South America. METHODS: A
      comparative genomic analysis was performed to determine putative causations
      stemming from ZIKV. RESULTS: Phylogenetic analyses integrating geographical and
      time factors revealed that Southeast Asian ZIKV might not be the direct source of
      South American outbreaks as previously speculated. Amino acid residues unique to
      South American ZIKV isolates at the envelope, pr and NS1 proteins are listed and
      shown in the structural context. These unique residues on external viral proteins
      are not found in Southeast Asian ZIKV and could be responsible for the ongoing
      outbreak either via an intrinsic property of the virus or interactions with human
      immunity. Only a selected few primer/probe sets currently in clinical use were
      identified of being capable of detecting ZIKV strains worldwide. The envelope
      proteins of dengue virus (DENV) and ZIKV also showed a remarkable degree of
      similarity especially at the surface residues. CONCLUSIONS: These findings may
      help explain the cross-reactivity of DENV antibodies to ZIKV. Thus, major caveats
      must be exercised in using existing diagnostic tools for ZIKV.

PMID- 27890364
TI  - Epidemiological status of malaria in Iran, 2011-2014.
AB  - OBJECTIVES: To aim to determine the status and epidemiological aspects of malaria
      in Iran in favour of gaining a better understanding of the national control of
      malaria. METHODS: This epidemiological study examined the status of malaria from
      2011 to 2014 in Iran. Data were collected from the Ministry of Health's protocol
      for controlling and eliminating malaria, which is currently in use. This malaria
      information reporting system is automated in all Iranian provinces and cities,
      and all information is submitted online to the center for communicable disease
      control in the Ministry of Health. Information about malaria is available for
      researchers to evaluate. RESULTS: The incidence rates decreased from 2011 to
      2014. There were 4.76, 2.12, 1.80, and 1.59 per 100000 people, respectively from
      2011 to 2014. During the four-year period (2011-2014), the highest numbers of
      cases occurred in those aged 16-25 years, by age, and in men, by sex. Most of the
      cases were workers and located in rural areas. An average 52.58% of cases were
      Iranian. The highest incidence rates from 2011 to 2014 were located in Sistan and
      Baluchestan province. There were 89.94, 43.9, 38.3, and 30.66 per 100000 people.
      The highest numbers of malaria cases were recorded in the cities Sarbaz,
      Nickshahr, and Chabahar in Sistan and Baluchestan province and Bandar Abbas,
      Bandar Jask, and Bandar Lengeh in Hormozgan province. During the four-year
      period, 57.05% of cases were caused by imported factors. The majority of cases
      were related to the trophozoite lifecycle of parasites. Regarding surveillance,
      there was inactive care in the majority of cases. Vivax malaria was the most
      prevalent. CONCLUSIONS: Despite the recently declining trend in reported cases,
      the expansion of local transmission, especially in areas with cross-border
      travel, is very worrying. Improved malaria control interventions can be effective
      for elimination of malaria in Iran; these can include programs to control border
      travel and focused interventions for high incidence areas and high-risk groups
      such as rural residents, men, workers, and people <35 years old.

PMID- 27890365
TI  - Protoscolicidal and immunomodulatory activity of Ziziphora tenuior extract and
      its fractions.
AB  - OBJECTIVE: To evaluate the scolicidal and immunomodulatory effect of the
      Ziziphora tenuior (Z. tenuior) extract and its fractions. METHODS: Protoscolices
      were treated with six concentrations (3, 5, 10, 25, 50, and 100 mg/mL) of Z.
      tenuior extract and its fractions (ethanol, petroleum ether, ethyl acetate and
      chloroform) in periods of 10, 20, 30, 40, 50 and 60 min, and viability of
      protoscolices was evaluated using the 1.0% eosin. To examine the immunomodulatory
      effects of Ziziphora and its fractions on macrophage cells, the non-toxic
      concentration of extract and different fractions determined by MTT assay, and the
      Griess reaction was used to measure the level of nitrite as an indicator of
      nitric oxide by the macrophage cells in 10, 100 and 200 MUg/mL in 24 h at 37 
      degrees C. RESULTS: In this study, the Z. tenuior extract at 10 mg/mL
      concentration was able to kill all protoscolices during 20 min. By increasing the
      concentration to 25 mg/mL, the scolicidal time reduced to 10 min. Regarding the
      effect of different fractions of Z. tenuior, the ethanolic fraction showed the
      highest scolicidal activity. The extract demonstrated an inhibitory effect on the
      activity of macrophages and reduced nitric oxide production. Although the
      petroleum ether and ethanolic fractions of the extract reduced nitric oxide
      production, nevertheless, this effect was only significant at 10 and 100 MUg/mL
      concentrations (P < 0.05). CONCLUSION: The Z. tenuior extract and its fractions
      were effective against protoscolices yet the effect of total extract was
      considerable. Our findings indicates that the extract and its ethanolic and
      petroleum ether fractions could have anti-inflammatory properties.

PMID- 27890366
TI  - In vitro biofilm formation in ESBL producing Escherichia coli isolates from cage
      birds.
AB  - OBJECTIVE: To determine biofilm and hydrophobicity formation ratios in extended
      spectrum beta lactamases (ESBL) synthesizing Escherichia coli isolates which were
      isolated from feces samples of 150 cage bird species randomly taken from pet
      shops in Hatay province, Turkey. METHODS: In vitro biofilm production of 4 ESBL
      positive isolates were performed by Congo Red Agar (CRA), Standard Tube (ST) and
      Microtitre Plate (MP) methods while their hydrophobicity were examined by
      bacterial adhesion to hydrocarbon (BATH) test. RESULTS: In the examined isolates,
      while biofilm production was found to be negative by CRA method, highest biofilm
      producing strain, among 4 bacteria was determined to be A42 by ST and MP methods.
      The Scanning Electron Microscopy (SEM) also displayed these confirmed findings.
      The hydrophobicity values of strains were determined to be between 22.45% and
      26.42%. CONCLUSIONS: As a result, biofilm formation in cage bird feces originated
      ESBL positive Escherichia coli isolates was performed for the first time in
      Turkey. In order to present the relation between pathogenicity and biofilm
      production in animal originated ESBL positive isolates, further studies are
      required.

PMID- 27890367
TI  - Evaluation of interleukin 8 +2767 A/T polymorphism in visceral leishmaniasis.
AB  - OBJECTIVE: To evaluated the relationship between the genetic variations at IL-8
      +2767 position with VL pathogenesis among Iranian patients. METHODS: Three groups
      including patients with VL clinical presentation and leishmania seropositive (n =
      124), patients seropositive but without clinical presentation (n = 82) and
      healthy controls (n = 63) were selected to conduct this cross-sectional study.
      Polymorphism at +2767 position of IL-8 was investigated using PCR-RFLP
      techniques. Anti-leishmania antibody titration was evaluated by the
      immunoflorescence technique. RESULTS: We observed higher significant frequencies
      +2767 A/A and A/T genotypes in Group 1 compared to Group 2 and healthy controls
      (P = 0.001). Also, patients in Group 1 carrying A/A genotype showed higher titer
      of anti-leishmania antibody than patients with A/T and T/T genotypes (P = 0.05).
      The validity of the data was analyzed using Hardy-Weinberg equilibrium and one
      way analysis of variance (ANOVA), as well as chi2 tests. CONCLUSIONS: Our
      findings indicate that the IL-8 +2767 polymorphism is significantly involved in
      impaired immune responses against VL and it could be considered as a risk factor
      for the VL progress.

PMID- 27890368
TI  - Effect of Glycyrrhiza uralensis Fisch polysaccharide on growth performance and
      immunologic function in mice in Ural City, Xinjiang.
AB  - OBJECTIVE: To discuss the effect of Glycyrrhiza uralensis (G. uralensis) Fisch
      polysaccharide on growth performance and immunologic function in mice in Ural
      City, Xinjiang and to provide important data supporting the application of
      Glycyrrhiza polysaccharide. METHODS: A total of 100 Kunming mice aged 3 weeks old
      were randomly divided into 5 groups with 20 mice in each group (10 were females
      and 10 were males). About 0.5 mL normal saline was given to the mice of control
      group every day and 0.5 mL G. uralensis Fisch polysaccharide was given to the
      mice of other groups at the concentration of 1, 20, 50 and 100 mg/mL,
      respectively. The growth performance (average body weight, average daily feed
      intake and feed efficiency), immune organ indexes (spleen index and thymus index)
      and immunologic function (serum IL-2, CD4+/CD8+ and the activity of NK cells) of
      mice in each group were detected continuously. RESULTS: The average body weight,
      feed efficiency, serum IL-2, CD4+/CD8+ and the activity of NK cells of mice were
      increased with the increase of administrated time after administrating G.
      uralensis Fisch polysaccharide and were reached up the largest level on Day 28.
      At the same time, each index was proportional to the given dose and was
      significantly higher than those of control group and reached up the largest level
      at the administrated dose of 100 mg/mL. After administrating G. uralensis Fisch
      polysaccharide, the spleen index and thymus index of mice were increased with the
      increase of administrated dose and the spleen index and thymus index of mice
      administrated with the dose of 100 mg/mL were maximum which was more than 1.51
      times and 1.43 times of that in control group, respectively and the comparative
      differences showed statistical significance (P < 0.05). The average daily feed
      intake of mice in each group was increased with the passage of time and at the
      same time, the comparison of average daily feed intake of mice in each group was
      not significantly different (P > 0.05). CONCLUSIONS: G. uralensis Fisch
      polysaccharide can significantly improve the growth performance and immunologic
      function of mice and laid a research basis for the clinical application of G.
      uralensis Fisch polysaccharide.

PMID- 27890369
TI  - Anti-tumor activity of tanshinone IIA in combined with cyclophosphamide against
      Lewis mice with lung cancer.
AB  - OBJECTIVE: To explore the anti-tumor activity of tanshinone IIA in combined with
      cyclophosphamide against Lewis mice with lung cancer and the effect on cellular
      immune function. METHODS: Lewis tumor cells were inoculated subcutaneously into
      the right armpit of mice in each group (n = 20) to establish Lewis lung cancer
      mice model. After model establishment, mice in the model group were given normal
      saline by lavage, qd. Mice in treatment I group were given intraperitoneal
      injection of Tan IIA, 15 mg/kg, qd. Mice in treatment II group were given
      intraperitoneal injection of CTX, 25 mg/kg, qd. Mice in treatment III group were
      given intraperitoneal injections of Tan IIA and CTX, in which the administration
      method of Tan IIA was the same as in treatment I group, continuously for 2 weeks,
      and the dosage of CTX was the same as in treatment II group, 24 h after model
      establishment, every other day. Mice were sacrificed 2 weeks after establishment.
      The tumor tissues were collected to calculate the anti-tumor rate.
      Immunohistochemistry was used to detect the expressions of Bcl-2, Bax, VEGF,
      Angiostatin, and Endostatin. FCM was used to detect T lymphocyte subsets in
      spleen and liver of mice. RESULTS: The tumor weight in treatment I, II, and III
      groups was significantly lower than that in the model group (P < 0.05). The tumor
      weight in treatment III group was significantly lower than that in treatment I
      and II groups (P < 0.05). The anti-tumor rate in treatment II and III groups was
      significantly higher than that in treatment I group (P < 0.05). Bcl-2 expression
      in the tumor tissues of treatment I, II, and III groups was significantly lower
      than that in the model group (P < 0.05), while Bax expression was significantly
      higher than that in the model group (P < 0.05). Bcl-2 expression in the tumor
      tissues of treatment I and II groups was significantly higher than that in
      treatment III group (P < 0.05), while Bax expression was significantly lower than
      that in treatment III group (P < 0.05). CD4+ and CD4+/CD8+ in treatment I, II,
      and III groups were significantly higher than those in the model group (P <
      0.05). CD4+ in treatment III group was significantly higher than that in
      treatment I and II groups (P < 0.05), while CD4+/CD8+ was significantly higher
      than that in treatment II group (P < 0.05). The comparison of CD8+ among each
      group was not statistically significant (P > 0.05). NK cell activity in treatment
      I, II, and III groups was significantly higher than that in the model group (P <
      0.05). NK cell activity in treatment III group was significantly higher than that
      in treatment I and II groups (P < 0.05). CONCLUSIONS: Tan IIA in combined with
      CTX can down regulate Bcl-2 expression in lung cancer tissues, up regulate Bax
      expression, inhibit the neovascularization of tumor tissues, and enhance the
      immunological function, with a significant anti-tumor activity.

PMID- 27890370
TI  - Acetylcholinesterase, butyrylcholinesterase and paraoxonase 1 activities in rats
      treated with cannabis, tramadol or both.
AB  - OBJECTIVE: To investigate the effect of Cannabis sativa resin and/or tramadol,
      two commonly drugs of abuse on acetylcholinesterase and butyrylcholinesterase
      activities as a possible cholinergic biomarkers of neurotoxicity induced by these
      agents. METHODS: Rats were treated with cannabis resin (5, 10 or 20 mg/kg)
      (equivalent to the active constituent Delta9-tetrahydrocannabinol), tramadol (5,
      10 and 20 mg/kg) or tramadol (10 mg/kg) combined with cannabis resin (5, 10 and
      20 mg/kg) subcutaneously daily for 6 weeks. Acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) activities were measured in brain and serum. We also
      measured the activity of paraoxonase-1 (PON1) in serum of rats treated with these
      agents. RESULTS: (i) AChE activity in brain increased after 10-20 mg/kg cannabis
      resin (by 16.3-36.5%). AChE activity in brain did not change after treatment with
      5-20 mg/kg tramadol. The administration of both cannabis resin (5, 10 or 20
      mg/kg) and tramadol (10 mg/kg) resulted in decreased brain AChE activity by
      14.1%, 12.9% and 13.6%, respectively; (ii) BChE activity in serum was markedly
      and dose-dependently inhibited by cannabis resin (by 60.9-76.9%). BChE activity
      also decreased by 17.6-36.5% by 10-20 mg/kg tramadol and by 57.2-63.9% by the
      cannabis resin/tramadol combined treatment; (iii) Cannabis resin at doses of 20
      mg/kg increased serum PON1 activity by 25.7%. In contrast, tramadol given at 5,
      10 and 20 mg/kg resulted in a dose-dependent decrease in serum PON1 activity by
      19%, 36.7%, and 46.1%, respectively. Meanwhile, treatment with cannabis resin
      plus tramadol resulted in 40.2%, 35.8%, 30.7% inhibition of PON1 activity
      compared to the saline group. CONCLUSIONS: These data suggest that cannabis resin
      exerts different effects on AChE and BChE activities which could contribute to
      the memory problems and the decline in cognitive function in chronic users.

PMID- 27890371
TI  - Mechanism of action of Zhuyu Annao pill in mice with cerebral intrahemorrhage
      based on TLR4.
AB  - OBJECTIVE: To explore the protective effect and possible mechanism of action of
      Zhuyu Annao pill in mice with intracerebral hemorrhage (ICH). METHODS: Sixty mice
      were divided into the control group, hemorrhage group, drug-treated group (after
      hemorrhage), TLR4-knockout hemorrhage group and TLR4-knockout hemorrhage + drug
      treated group (after hemorrhage) with 12 in each group. Model of autologous ICH
      was established in all groups. After drilling and 12 h of fasting, models in the
      control group hemorrhage group and TLR4-knockout hemorrhage group were all
      drenched with 10 mL/kg distilled water by intragastric administration. Models in
      the drug-treated group and TLR4-knockout hemorrhage + drug-treated group were
      drenched with 6.25 g/kg of Zhuyu Annao pill. All groups were treated for 7 d.
      Longa scoring method was used to measure the neurological defect scores and
      determine the brain water contents of all groups; ELISA was employed to detect
      the inflammatory factor interleukin (IL)-6, tumor necrosis factor-alpha (TNF
      alpha) and IL-1beta in brain tissues; and Western blot was applied to test the
      expression quantities of apoptotic protein Bax and anti-apoptotic protein Bcl-2
      in brain tissues. RESULTS: At day 3 and 7, compared with the hemorrhage group,
      the neurological defect scores of the drug-treated group, TLR4-knockout
      hemorrhage group and TLR4-knockout hemorrhage + drug-treated group decreased
      significantly (P < 0.05). Compared with the hemorrhage group, the brain water
      contents of the drug-treated group, TLR4-knockout hemorrhage group and TLR4
      knockout hemorrhage + drug-treated group reduced significantly (P < 0.05).
      Compared with the hemorrhage group, the inflammatory factor IL-6, TNF-alpha and
      IL-1beta of the drug-treated group, TLR4-knockout hemorrhage group and TLR4
      knockout hemorrhage + drug-treated group decreased significantly (P < 0.05).
      Compared with the hemorrhage group, the expression of apoptotic protein Bax of
      the drug-treated group, TLR4-knockout hemorrhage group and TLR4-knockout
      hemorrhage + drug-treated group decreased significantly and the expression of
      anti-apoptotic protein Bcl-2 increased significantly (P < 0.05). CONCLUSIONS:
      Zhuyu Annao pill can alleviate encephaledema for mice with ICH and reduce
      inflammatory responses and nerve cell apoptosis. TLR4 can mediate inflammatory
      injury induced by ICH. Thus, Zhuyu Annao pill can play a protective role for
      brains by decreasing the expression of TLR4.

PMID- 27890372
TI  - Protective effect of antioxidant on renal damage caused by doxorubicin
      chemotherapy in mice with hepatic cancer.
AB  - OBJECTIVES: To investigate the protective effects and mechanism of antioxidant
      TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic
      cancer. METHODS: Cell H22 of mice with hepatic cancer which was subcultured for
      three times was subcutaneously transplanted to the groin of right lower limb of
      45 SPF Kunming mice to establish the transplanted tumor model. The doxorubicin
      chemotherapy group and antioxidant intervention group received intraperitoneal
      injection of ADM (1 mg/kg.0.2 mL/2 d). The model control group received normal
      saline (NS) of the same volume at the same time. 1% TBHQ was added into the diet
      of mice of the antioxidant intervention group. Seven weeks later, morning urines
      and peripheral blood were randomly collected to detect UAlb, UCr, BUN, Scr and
      UAlb/Cr levels. All mice were beheaded. The renal tissues were made into
      homogenate, and SOD, T-AOC and MDA content in tissues were detected followed by
      cell lysis. All data were processed using SPSS19.0. RESULTS: The UAlb/Cr, BUN,
      Scr and MDA of doxorubicin chemotherapy group were significantly higher those of
      model control group and the activities of SOD, T-AOC in doxorubicin chemotherapy
      group were lower than those of model control group (P < 0.01). The UAlb/Cr, BUN,
      Scr and MDA of antioxidant intervention group were lower than those of
      doxorubicin chemotherapy group and the activities of SOD, T-AOC of antioxidant
      intervention group were higher than those of doxorubicin chemotherapy group
      doxorubicin chemotherapy group (P < 0.05). The BUN of model control group was
      higher than that of blank group, and T-AOC was lower than that of blank group,
      and difference was statistically significant (P < 0.05). CONCLUSIONS: Doxorubicin
      chemotherapy could lead to abnormal antioxidant capacity and renal function of
      tumor-bearing mice with hepatic cancer. TBHQ antioxidant intervention could
      effectively improve the antioxidant capacity of renal tissue and reduce the renal
      damage caused by doxorubicin to some extent.

PMID- 27890373
TI  - Expression and mechanism of action of miR-196a in epithelial ovarian cancer.
AB  - OBJECTIVE: To explore the expression, biological function and possible mechanism
      of action of microRNA molecular-196a (miR-196a) in epithelial ovarian cancer.
      METHODS: RT-PCR was used to detect the expression quantities of epithelial
      ovarian tissue, benign ovarian tissue, normal ovary epithelial tissue, ovarian
      cancer cell lines and miR-196a in normal ovarian epithelial cells to analyze the
      relationship between the expression of miR-196a and the clinical pathologic
      parameters of ovarian cancer. Among those cell lines, the cell line of which miR
      196a expressed the most or least was selected and transfected the ovarian cancer
      cell line by using negative control plasma and miR-196a inhibitor. After
      transfection, RT-PCR was used to test the expression quantity of miR-196a,
      Transwell chamber method was applied to determine the migration and invasion
      abilities of ovarian carcinoma cells and Western blot was employed to detect the
      expression of HOXA10 protein. RESULTS: The relative expression quantities of miR
      196a in ovarian cancer tissue and benign ovarian tissue were significantly higher
      than that in normal ovarian epithelial tissue, and the expression quantity of miR
      196a in ovarian cancer tissue was distinctively higher than that in benign
      ovarian tissue (P < 0.05). Among 78 cases of epithelial ovarian cancer, the
      expression quantities of miR-196a in patients with low differentiation were all
      significantly higher than those in patients with high differentiation (P < 0.05).
      The expression of miR-196a showed no significant relation with age, clinical
      stage and whether CA125 was positive or not in patients (P > 0.05). Compared with
      normal ovarian epithelial cell line IOSE80, the expression quantities of miR-196a
      of all ovarian cancer cell lines increased obviously and differences were
      statistically significant (P < 0.05). Among them, the expression of miR-196a of
      ovarian cancer cell line SKOV3 was the highest, while it decreased significantly
      (4.678 +/- 0.785 vs. 2.131 +/- 0.345, t = 2.938, P < 0.05) after the ovarian
      cancer cell line SKOV3 was transfected by miR-196a inhibitor. The results of
      Transwell chamber method showed that the migration and invasion abilities of
      ovarian cancer cells SKOV3 were declined significantly after the expression of
      miR-196a was down-regulated and the difference showed statistical significance (P
      < 0.05). The results of Western blot revealed that the relative expression of
      HOXA10 decreased distinctly after the expression of miR-196a was down-regulated
      and also the difference showed statistical significance (P < 0.05). CONCLUSIONS:
      The miR-196a might serve as a cancer-promoting gene to promote the migration and
      invasion of epithelial ovarian cancer by downstream target gene HOXA10.

PMID- 27890374
TI  - Clinical significance of dynamic detection for serum levels of MCP-1, TNF-alpha
      and IL-8 in patients with acute pancreatitis.
AB  - OBJECTIVE: To observe dynamic changes of levels of monocyte chemotactic protein-1
      (MCP-1), tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in
      patients with acute pancreatitis and to investigate its evaluation value on the
      severity of acute pancreatitis. METHODS: A total of 109 patients with acute
      pancreatitis admitted were divided into mild acute pancreatitis group (MAP group,
      42 cases), moderately severe acute pancreatitis (MSAP group, 35 cases) and severe
      acute pancreatitis (SAP group, 32 cases). ELISA was used to detect the serum
      levels of MCP-1, TNF-alpha and IL-8 of patients at day 1, day 4 and day 7 of
      admission to hospital. RESULTS: The serum levels of MCP-1, TNF-alpha and IL-8
      from MAP group, MSAP group and SAP group at day 1 of admission to hospital all
      significantly increased. There was a significant difference between MAP group and
      control group, MSAP group and MAP group, SAP group and MSAP group (P < 0.05). The
      serum concentrations of IL-8 from MASP group and SAP group obviously increased at
      day 1, and there was significant difference between MASP group and MAP group, SAP
      group and MSAP group (P < 0.05), while the difference between MAP group and
      control group was not obvious (P > 0.05); The serum concentrations of MCP-1, TNF
      alpha and IL-8 from MAP group all reached the highest level at day 4, which were
      significantly higher than the detection levels at day 1. In MSAP group and SAP
      group, the serum concentrations of MCP-1, TNF-alpha and IL-8 were the highest at
      day 1, which were significantly higher than the detection levels at day 4 and 7.
      At each detecting timing, the serum concentrations of MCP-1, TNF-alpha and IL-8
      from MSAP group and SAP group were all higher than those of MAP group and MSAP
      group, respectively. CONCLUSIONS: The dynamic changes of serum levels of MCP-1,
      TNF-alpha and IL-8 in patients with acute pancreatitis have their rules, and the
      change rule of MAP group was different with that of MSAP and SAP group, which
      showed the reference value for the diagnosis and illness severity evaluation of
      acute pancreatitis.

PMID- 27890376
TI  - Based on the risk of dengue virus transmission via blood transfusion: What about
      the risk in case of Zika virus?

PMID- 27890375
TI  - Modifiable determinants of attitude towards dengue vaccination among healthy
      inhabitants of Aceh, Indonesia: Findings from a community-based survey.
AB  - OBJECTIVE: To explore and understand the attitude towards dengue vaccination and
      its modifiable determinants among inhabitants of Aceh (northern Sumatra Island,
      Indonesia), the region that was most severely affected by the earthquake and
      tsunami of 26 December 2004. METHODS: A community-based, cross-sectional study
      was conducted among 535 healthy inhabitants in nine regencies (Kabupaten or
      Kotamadya) of Aceh that were selected randomly from November 2014 to March 2015.
      A set of validated, pre-tested, structured questionnaires was used to guide the
      interviews. The questionnaires covered a range of explanatory variables and one
      outcome variable (attitude to dengue vaccination). Multi-step logistic regression
      analysis and Spearman's rank correlation were used to test the role of
      explanatory variables for the outcome variable. RESULTS: More than 70% of the
      participants had a poor attitude towards dengue vaccination. Modifiable
      determinants associated with poor attitude to dengue vaccination were low
      education level, working as farmers and traditional market traders, low
      socioeconomic status and poor knowledge, attitude and practice regarding dengue
      fever (P < 0.05). The KAP domain scores were correlated strongly with attitude to
      dengue vaccination, rs = 0.25, rs = 0.67 and rs = 0.20, respectively (P < 0.001).
      Multivariate analysis found that independent predictors associated with attitude
      towards dengue vaccination among study participants were only sex and attitude
      towards dengue fever (P < 0.001). CONCLUSIONS: This study reveals that low KAP
      regarding dengue fever, low education level and low socioeconomic status are
      associated with a poor attitude towards dengue vaccination. Therefore,
      inhabitants of suburbs who are working as farmers or traditional market traders
      with low socioeconomic status are the most appropriate target group for a dengue
      vaccine introduction program.

PMID- 27890377
TI  - Corrigendum to "CETP polymorphisms confer genetic contribution to centenarians of
      Hainan, south of China" [Asian Pac J Trop Med 9 (9) (2016) 872-876].

PMID- 27890378
TI  - Design and synthesis of 4,5,6,7-tetrahydro-1H-1,2-diazepin-7-one derivatives as a
      new series of Phosphodiesterase 4 (PDE4) inhibitors.
AB  - Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in
      respiratory, inflammatory, metabolic and CNS disorders. The present work details
      the design, chemical exploration and biological profile of a novel PDE4 inhibitor
      chemotype. A diazepinone ring was identified as an under-represented heterocyclic
      system fulfilling a set of PDE4 structure-based design hypotheses. Rapid
      exploration of the structure activity relationships for the series was enabled by
      robust and scalable two/three-steps parallel chemistry protocols. The resulting
      compounds demonstrated PDE4 inhibitory activity in cell free and cell-based
      assays comparable to the Zardaverine control used, suggesting potential avenues
      for their further development.

PMID- 27890379
TI  - Synthesis, characterization and antineoplastic activity of bis-aziridinyl dimeric
      naphthoquinone - A novel class of compounds with potent activity against acute
      myeloid leukemia cells.
AB  - The synthesis, characterization and antileukemic activity of rationally designed
      amino dimeric naphthoquinone (BiQ) possessing aziridine as alkylating moiety is
      described. Bis-aziridinyl BiQ decreased proliferation of acute myeloid leukemia
      (AML) cell lines and primary cells from patients, and exhibited potent
      (nanomolar) inhibition of colony formation and overall cell survival in AML
      cells. Effective production of reactive oxygen species (ROS) and double stranded
      DNA breaks (DSB) induced by bis-aziridinyl BiQ is reported. Bis-dimethylamine
      BiQ, as the isostere of bis-aziridinyl BiQ but without the alkylating moiety did
      not show as potent anti-AML activity. Systemic administration of bis-aziridinyl
      BiQ was well tolerated in NSG mice.

PMID- 27890380
TI  - New polyhydroxytriterpenoid derivatives from fruits of Terminalia chebula Retz.
      and their alpha-glucosidase and alpha-amylase inhibitory activity.
AB  - Three new polyhydroxytriterpenoid derivatives, 23-O-neochebuloylarjungenin 28-O
      beta-d-glycopyranosyl ester (1), 23-O-4'-epi-neochebuloylarjungenin (2), and 23-O
      galloylpinfaenoic acid 28-O-beta-d-glucopyranosyl ester (17) were isolated from
      the fruits of Terminalia chebula Retz. along with fourteen known ones. Their
      structures were elucidated by 1D and 2D NMR spectroscopic data and acid
      hydrolysis. After evaluating for Baker's yeast alpha-glucosidase, rat intestinal
      alpha-glucosidase, and porcine pancreatic alpha-amylase inhibitory activities of
      all the isolated compounds, 23-O-galloylarjunolic acid (11, IC50 21.7MUM) and 23
      O-galloylarjunolic acid 28-O-beta-d-glucopyranosyl ester (12, IC50 64.2MUM)
      showed potent inhibitory activities against Baker's yeast alpha-glucosidase
      compared to the positive control, acarbose (IC50 174.0MUM). However, all the
      tested compounds except for the positive control, acarbose, had no or only weak
      inhibitory activity against rat intestinal alpha-glucosidase and porcine
      pancreatic alpha-amylase.

PMID- 27890381
TI  - Evaluation of dipeptide nitriles as inhibitors of rhodesain, a major cysteine
      protease of Trypanosoma brucei.
AB  - A series of dipeptide nitriles known as inhibitors of mammalian cathepsins were
      evaluated for inhibition of rhodesain, the cathepsin L-like protease of
      Trypanosoma brucei. Compound 35 consisting of a Leu residue fitting into the S2
      pocket and a triarylic moiety consisting of thiophene, a 1,2,4-oxadiazole and a
      phenyl ring fitting into the S3 pocket, and compound 33 with a 3-bromo-Phe
      residue (S2) and a biphenyl fragment (S3) were found to inhibit rhodesain in the
      single-digit nanomolar range. The observed steep structure-activity relationship
      could be explained by covalent docking simulations. With their high selectivity
      indices (ca. 200) and the good antitrypanosomal activity (8MUM) the compounds
      represent promising starting points for new rhodesain inhibitors.

PMID- 27890382
TI  - [Alzheimer's disease cerebro-spinal fluid biomarkers: A clinical research tool
      sometimes useful in daily clinical practice of memory clinics for the diagnosis
      of complex cases].
AB  - The role of biomarkers in clinical research was recently highlighted in the new
      criteria for the diagnosis of Alzheimer's disease. Cerebro-spinal fluid (CSF)
      biomarkers (total Tau protein, threonine 181 phosphorylated Tau protein and
      amyloid Abeta1-42 peptide) are associated with cerebral neuropathological lesions
      observed in Alzheimer's disease (neuronal death, neurofibrillary tangle with
      abnormal Tau deposits and amyloid plaque). Abeta1-40 amyloid peptide dosage helps
      to interpret Abeta1-42 results. As suggested in the latest international criteria
      and the French HAS (Haute Autorite de sante) recommendations, using theses CSF
      biomarkers should not be systematic but sometimes could be performed to improve
      confidence about the diagnostic of Alzheimer's disease in young subjects or in
      complex clinical situations. Future biomarkers actually in development will
      additionally help in diagnostic process (differential diagnosis) and in
      prognostic evaluation of neurodegenerative diseases.

PMID- 27890383
TI  - [Autoimmune and inflammatory disorders associated with lymphoid hematological
      malignancies].
AB  - In this literature review, we reported autoimmune and inflammatory disorders
      associated with lymphoid hematological malignancies, including non-Hodgkin's
      lymphoma, Hodgkin's lymphoma and chronic lymphocytic leukemia. The different
      types of systemic involvement are classified by affected organ. We listed in this
      review the joint diseases, skin, neurologic, hematologic, renal, and vasculitis.
      We tried to determine whether there is a correlation between each autoimmune
      manifestation and a specific type of lymphoma or a particular feature that may
      support a paraneoplastic origin, if there is an impact on the prognosis of the
      hematological malignancy, and finally, we identified the different therapeutic
      strategies used in the literature.

PMID- 27890384
TI  - Re: Omar Fahmy, Mohd Ghani Khairul-Asri, Christian Schwentner, et al. Algorithm
      for Optimal Urethral Coverage in Hypospadias and Fistula Repair: A Systematic
      Review. Eur Urol 2016;70:293-8.

PMID- 27890385
TI  - Common hepatitis C treatment side effects in relation to alcohol consumption and
      racial differences in Southeastern Taiwan.

PMID- 27890387
TI  - Laparoscopic resection of a paraganglioma in the organ of Zuckerkandl 123I
      metaiodobenzylguanidine guided by gamma probe.

PMID- 27890386
TI  - 2016 Guidelines of the Taiwan Heart Rhythm Society and the Taiwan Society of
      Cardiology for the management of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia. Both the
      incidence and prevalence of AF are increasing, and the burden of AF is becoming
      huge. Many innovative advances have emerged in the past decade for the diagnosis
      and management of AF, including a new scoring system for the prediction of stroke
      and bleeding events, the introduction of non-vitamin K antagonist oral
      anticoagulants and their special benefits in Asians, new rhythm- and rate-control
      concepts, optimal endpoints of rate control, upstream therapy, life-style
      modification to prevent AF recurrence, and new ablation techniques. The Taiwan
      Heart Rhythm Society and the Taiwan Society of Cardiology aimed to update the
      information and have appointed a jointed writing committee for new AF guidelines.
      The writing committee members comprehensively reviewed and summarized the
      literature, and completed the 2016 Guidelines of the Taiwan Heart Rhythm Society
      and the Taiwan Society of Cardiology for the Management of Atrial Fibrillation.
      This guideline presents the details of the updated recommendations, along with
      their background and rationale, focusing on data unique for Asians. The
      guidelines are not mandatory, and members of the writing committee fully realize
      that treatment of AF should be individualized. The physician's decision remains
      most important in AF management.

PMID- 27890388
TI  - Uganda experience-Using cost assessment of an established registry to project
      resources required to expand cancer registration.
AB  - BACKGROUND: The objectives of this study are (1) to estimate the cost of
      operating the Kampala Cancer Registry (KCR) and (2) to use cost data from the KCR
      to project the resource needs and cost of expanding and sustaining cancer
      registration in Uganda, focusing on the recently established Gulu Cancer Registry
      (GCR) in rural Northern Uganda. METHODS: We used Centers for Disease Control and
      Prevention's (CDC's) International Registry Costing Tool (IntRegCosting Tool) to
      estimate the KCR's activity-based cost for 2014. We grouped the registry
      activities into fixed cost, variable core cost, and variable other cost
      activities. After a comparison KCR and GCR characteristics, we used the cost of
      the KCR to project the likely ongoing costs for the new GCR. RESULTS: The KCR
      incurred 42% of its expenditures in fixed cost activities, 40% for variable core
      cost activities, and the remaining 18% for variable other cost activities. The
      total cost per case registered was 28,201 Ugandan shillings (approximately US $10
      in 2014) to collect and report cases using a combination of passive and active
      cancer data collection approaches. The GCR performs only active data collection,
      and covers a much larger area, but serves a smaller population compared to the
      KCR. CONCLUSION: After identifying many differences between KCR and GCR that
      could potentially affect the cost of registration, our best estimate is that the
      GCR, though newer and in a rural area, should require fewer resources than the
      KCR to sustain operations as a stand-alone entity. The optimal structure of the
      GCR needs to be determined in the future.

PMID- 27890389
TI  - Heparanase confers a growth advantage to differentiating murine embryonic stem
      cells, and enhances oligodendrocyte formation.
AB  - Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells,
      play important roles in development and homeostasis. These molecules are located
      primarily on the cell surface and in the pericellular matrix, where they interact
      with a multitude of macromolecules, including many growth factors. Manipulation
      of the enzymes involved in biosynthesis and modification of HSPG structures
      alters the properties of stem cells. Here, we focus on the involvement of
      heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in
      differentiation of embryonic stem cells into the cells of the neural lineage.
      Embryonic stem (ES) cells overexpressing HPSE (Hpse-Tg) proliferated more rapidly
      than WT ES cells in culture and formed larger teratomas in vivo. In addition,
      differentiating Hpse-Tg ES cells also had a higher growth rate, and
      overexpression of HPSE in NSPCs enhanced Erk and Akt phosphorylation. Employing a
      two-step, monolayer differentiation, we observed an increase in HPSE as wild-type
      (WT) ES cells differentiated into neural stem and progenitor cells followed by
      down-regulation of HPSE as these NSPCs differentiated into mature cells of the
      neural lineage. Furthermore, NSPCs overexpressing HPSE gave rise to more
      oligodendrocytes than WT cultures, with a concomitant reduction in the number of
      neurons. Our present findings emphasize the importance of HS, in neural
      differentiation and suggest that by regulating the availability of growth factors
      and, or other macromolecules, HPSE promotes differentiation into
      oligodendrocytes.

PMID- 27890390
TI  - World Association of Sleep Medicine (WASM) 2016 standards for recording and
      scoring leg movements in polysomnograms developed by a joint task force from the
      International and the European Restless Legs Syndrome Study Groups (IRLSSG and
      EURLSSG).
AB  - This report presents the results of the work by a joint task force of the
      International and European Restless Legs Syndrome Study Groups and World
      Association of Sleep Medicine that revised and updated the current standards for
      recording and scoring leg movements (LM) in polysomnographic recordings (PSG).
      First, the background of the decisions made and the explanations of the new rules
      are reported and then specific standard rules are presented for recording,
      detecting, scoring and reporting LM activity in PSG. Each standard rule has been
      classified with a level of evidence. At the end of the paper, Appendix 1 provides
      algorithms to aid implementation of these new standards in software tools. There
      are two main changes introduced by these new rules: 1) Candidate LM (CLM), are
      any monolateral LM 0.5-10 s long or bilateral LM 0.5-15 s long; 2) periodic LM
      (PLM) are now defined by runs of at least four consecutive CLM with an
      intermovement interval >=10 and <= 90 s without any CLM preceded by an interval
      <10 s interrupting the PLM series. There are also new options defining CLM
      associated with respiratory events. The PLM rate may now first be determined for
      all CLM not excluding any related to respiration (providing a consistent number
      across studies regardless of the rules used to define association with
      respiration) and, subsequently, the PLM rate should also be calculated without
      considering the respiratory related events. Finally, special considerations for
      pediatric studies are provided. The expert visual scoringof LM has only been
      altered by the new standards to require accepting all LM > 0.5 s regardless of
      duration, otherwise the technician scores the LM as for the old standards. There
      is a new criterion for the morphology of LM that applies only to computerized LM
      detection to better match expert visual detection. Available automatic scoring
      programs will incorporate all the new rules so that the new standards should
      reduce technician burden for scoring PLMS.

PMID- 27890391
TI  - Public reporting of hospital quality shows inconsistent ranking results.
AB  - BACKGROUND: Evidence from the US has demonstrated that hospital report cards
      might generate confusion for consumers who are searching for a hospital. So far,
      little is known regarding hospital ranking agreement on German report cards as
      well as underlying factors creating disagreement. OBJECTIVE: This study examined
      the consistency of hospital recommendations on German hospital report cards and
      discussed underlying reasons for differences. METHODS: We compared hospital
      recommendations for three procedures on four German hospital report cards. The
      agreement between two report cards was determined by Cohen's-Kappa. Fleiss' kappa
      was applied to evaluate the overlap across all four report cards. RESULTS:
      Overall, 43.40% of all hospitals were labeled equally as low, middle, or top
      performers on two report cards (hip replacement: 43.2%; knee replacement: 42.8%;
      percutaneous coronary intervention: 44.3%). In contrast, 8.5% of all hospitals
      were rated a top performer on one report card and a low performer on another
      report card. The inter-report card agreement was slight at best between two
      report cards (kappamax=0.148) and poor between all four report cards
      (kappamax=0.111). CONCLUSIONS: To increase the benefit of public reporting,
      increasing the transparency about the concept of - medical - "quality" that is
      represented on each report card seems to be important. This would help patients
      and other consumers use the report cards that most represent one's individual
      preferences.

PMID- 27890392
TI  - Developments in home-care use. Policy and changing community-based care use by
      independent community-dwelling adults in the Netherlands.
AB  - Reforms have recently been introduced in the Dutch care system in order to
      constrain the rising expenditure on long-term care. In this study we examined
      changes in community-based care use between 2004 and 2011 and changes in the
      explanatory effects of its determinants (health, personal and facilitating
      factors) that may result from these reforms. The study drew on care use
      registration data linked to data from national health surveys and income data
      from the tax authorities. Changes in community-based care use determined by
      health, personal and facilitating factors between 2004 and 2011 were studied.
      Changes in determinants were investigated by incorporating time-interaction terms
      of each determinant in logistic regression models. The main findings show among
      other things that the use of community-based care did not increase between 2004
      and 2011 if allowances made for the increase in the number of (elderly) older
      people. The role of income and household composition has changed the most (and to
      a lesser extent the role of age and physical impairments). Care use decreased
      among individuals with high incomes and increased among single persons. The
      changes in community-based care use and in the role of income and household
      composition could be due to changes in eligibility for care, in which the
      applicant's personal situation is given a more prominent role alongside health
      considerations.

PMID- 27890393
TI  - Primary care managers' perceptions of their capability in providing care planning
      to patients with complex needs.
AB  - OBJECTIVES: The aim of this study was to investigate primary care managers'
      perceptions of their capability in providing care planning to patients with
      complex needs. Care planning is defined as a process where the patient, family
      and health professionals engage in dialogue about the patient's care needs and
      plan care interventions together. METHODS: Semi-structured interviews with 18
      primary care managers in western Sweden were conducted using Westrin's
      theoretical cooperation model. Data were analysed using a qualitative deductive
      method. MAIN FINDINGS: Results reveal that the managers' approach to care
      planning was dominated by non-cooperation and separation. The managers were
      permeated by uncertainty about the meaning of the task of care planning as such.
      They did not seem to be familiar with the national legislation stipulating that
      every healthcare provider must meet patients' need for care interventions and
      participate in the care planning. IMPLICATIONS FOR PRACTICE: To accomplish care
      planning, the process needs to cross - and overcome - both professional and
      organisational boundaries. There is also a need for incentives to develop working
      methods that promote local cooperation in order to facilitate optimal care for
      patients with complex needs.

PMID- 27890394
TI  - Purchase habits, use of paracetamol, and information sources on a reregulated
      Swedish pharmacy market: A population-based study.
AB  - Considering the general lack of knowledge on how over-the-counter paracetamol is
      used combined with the reported increase in paracetamol poisonings after the
      reregulation of the Swedish pharmacy market in 2009, we aimed to analyze purchase
      habits and use of paracetamol in Sweden. A further aim was to investigate sources
      of information about paracetamol. Data were collected in October 2015 through the
      Citizen Panel, a Web-based panel encompassing over 50,000 Swedes. A stratified
      sample of 6000 (aged 18 years and older) was emailed a survey invitation.
      Questions concerned paracetamol use, purchase habits and information sources. The
      participation rate was 58%. A majority (70.5%) reported use of paracetamol during
      the last three months. Purchasing paracetamol solely over-the-counter was most
      common (81.1%). Close to two-thirds usually purchased paracetamol at a pharmacy.
      However, it was more common to purchase OTC paracetamol at non-pharmacy outlets
      among younger compared to older respondents. The results of this study did not
      reveal any harmful paracetamol use. The most common information source overall
      was patient information leaflets, and it was significantly more common among the
      youngest compared to older subjects. Based on our results combined with previous
      research, we suggest more studies, both qualitative and quantitative, among young
      adults, both on the use of paracetamol and on the understanding of information in
      patient information leaflets and on the Internet.

PMID- 27890395
TI  - The recommodification of healthcare? A case study of user charges and
      inequalities in access to healthcare in Sweden 1980-2005.
AB  - BACKGROUND: User charges in Swedish healthcare have increased during recent
      decades. This can be seen in terms of the recommodification of healthcare: making
      healthcare access more dependent on market position. This study investigates
      whether the increase in user charges had an impact on educational inequalities in
      access to healthcare in Sweden between 1980 and 2005. METHODS: Data from the
      Swedish Living Conditions Survey were used to calculate the odds ratios of access
      to healthcare for the low and higher educated in Sweden, and the results were
      stratified by health status (Good and Not good health) for each year 1980-2005.
      These odds ratios were correlated with the average user charge for healthcare.
      RESULTS: There were no educational differences in healthcare access in the group
      with Good health. In the group with Not good health, the higher educated had
      higher rates of healthcare access than the lower educated. Inequalities in access
      to healthcare were relatively stable over time, with a slight increase among
      those with Not good health. DISCUSSION: Recommodification has had only a small
      association with access to healthcare in Sweden. The Swedish system has integral
      protections that protect the vulnerable against rising healthcare costs. This is
      an important caveat for other countries that are considering introducing or
      raising user charges.

PMID- 27890396
TI  - Structure-based design of broadly protective group a streptococcal M protein
      based vaccines.
AB  - BACKGROUND: A major obstacle to the development of broadly protective M protein
      based group A streptococcal (GAS) vaccines is the variability within the N
      terminal epitopes that evoke potent bactericidal antibodies. The concept of M
      type-specific protective immune responses has recently been challenged based on
      the observation that multivalent M protein vaccines elicited cross-reactive
      bactericidal antibodies against a number of non-vaccine M types of GAS.
      Additionally, a new "cluster-based" typing system of 175M proteins identified a
      limited number of clusters containing closely related M proteins. In the current
      study, we used the emm cluster typing system, in combination with computational
      structure-based peptide modeling, as a novel approach to the design of
      potentially broadly protective M protein-based vaccines. METHODS: M protein
      sequences (AA 16-50) from the E4 cluster containing 17 emm types of GAS were
      analyzed using de novo 3-D structure prediction tools and the resulting
      structures subjected to chemical diversity analysis to identify sequences that
      were the most representative of the 3-D physicochemical properties of the M
      peptides in the cluster. Five peptides that spanned the range of physicochemical
      attributes of all 17 peptides were used to formulate synthetic and recombinant
      vaccines. Rabbit antisera were assayed for antibodies that cross-reacted with E4
      peptides and whole bacteria by ELISA and for bactericidal activity against all
      E4GAS. RESULTS: The synthetic vaccine rabbit antisera reacted with all 17 E4M
      peptides and demonstrated bactericidal activity against 15/17 E4GAS. A
      recombinant hybrid vaccine containing the same E4 peptides also elicited
      antibodies that cross-reacted with all E4M peptides. CONCLUSIONS: Comprehensive
      studies using structure-based design may result in a broadly protective M peptide
      vaccine that will elicit cluster-specific and emm type-specific antibody
      responses against the majority of clinically relevant emm types of GAS.

PMID- 27890397
TI  - A general measles vaccination campaign in urban Guinea-Bissau: Comparing child
      mortality among participants and non-participants.
AB  - BACKGROUND: Measles vaccination campaigns targeting children aged 9-59months are
      conducted every three years in Guinea-Bissau. Studies have demonstrated
      beneficial non-specific effects of measles vaccine. We compared mortality one
      year after the December 2012 measles vaccination campaign in Bissau city for
      children who received campaign measles vaccine with children who did not receive
      campaign measles vaccine. METHODS: Field workers from Bandim Health Project
      registered all children living in the Bandim Health Project's study area who
      received measles vaccination at the campaign posts. Children not seen during the
      campaign were visited at home and campaign participation status was assessed. We
      compared mortality rates of participants vs. non-participants in Cox regression
      models. RESULTS: 5633 children aged 9-59months (85%) received campaign measles
      vaccination and 1006 (15%) did not. During the subsequent year 16 children died.
      Adjusted for background factors, the hazard ratio (HR) comparing measles
      vaccinated versus unvaccinated was 0.28 (95% CI: 0.10-0.77). The benefit was
      larger for girls (HR: 0.17 (0.05-0.59)) and for children who had received routine
      measles vaccine before the campaign (HR: 0.15 (0.04-0.63)). CONCLUSIONS: We found
      indications of strong beneficial non-specific effects of receiving measles
      vaccine during the 2012 campaign, especially for girls and children with previous
      routine measles vaccination. Measles vaccination campaigns may be an effective
      way of improving child survival.

PMID- 27890398
TI  - Influenza vaccination in people with type 2 diabetes, coverage, predictors of
      uptake, and perceptions. Result of the MADIABETES cohort a 7years follow up
      study.
AB  - OBJECTIVES: We aim to determine influenza vaccination uptake among people with
      diabetes included in the MADIABETES cohort study in order to identify predictors
      of uptake and to analyze reasons for adherence and non-adherence with
      vaccination. METHODS: Using data from the MADIABETES Study we conducted a
      retrospective case record form based study without controls. We included
      outpatients with type 2 diabetes mellitus. Information was obtained from
      computerized clinical records and by telephone survey. The main dependent
      variables were influenza vaccination uptake in the year 2013 and the reason for
      receiving or refusing vaccination. RESULTS: Overall, 65.7% had received the
      influenza vaccine in 2013. The mean number of influenza vaccines received from
      2007 to 2013 was 3.24 (SD1.15), although 19.23% had not received any influenza
      vaccine and 23.3% had been vaccinated against pneumococcus. The variables that
      increased the probability of being vaccinated were inclusion in the age-based
      recommendation (?60years), having a chronic respiratory disease, previous
      pneumococcal vaccination, higher number of visits to the general practitioner,
      higher number of influenza vaccines, and longer time since diabetes diagnosis. A
      higher mean glycated haemoglobin value in 2013 was associated with a reduced
      probability of vaccination. Most patients (90%) agreed to be vaccinated following
      their physician's advice because of their age or their chronic conditions. The
      most common reason for refusal among men was the belief that they were not at
      risk (41.6% vs. 29.79% in women); the most common reason for refusal among women
      was fear of adverse reactions (32.53% vs. 20.23% in men). CONCLUSIONS: The uptake
      of influenza vaccination among diabetic patients in the present study was below
      desirable levels. The main barrier to vaccination was lack of knowledge regarding
      the need for and risks and advantages of influenza vaccination. Healthcare
      professionals should educate and encourage influenza vaccination among people
      with diabetes.

PMID- 27890399
TI  - A partially purified outer membrane protein VirB9-1 for low-cost nanovaccines
      against Anaplasma marginale.
AB  - Anaplasma marginale is a devastating tick-borne pathogen causing anaplasmosis in
      cattle and results in significant economic loss to the cattle industry worldwide.
      Currently, there is no widely accepted vaccine against A. marginale. New
      generation subunit vaccines against A. marginale, which are much safer, more
      efficient and cost-effective, are in great need. The A. marginale outer membrane
      protein VirB9-1 is a promising antigen for vaccination. We previously have shown
      that soluble recombinant VirB9-1 protein can be expressed and purified from
      Escherichia coli and induce a high level of humoral and cellular immunity in
      mice. In this study, we re-formulated the nanovaccines using the partially
      purified VirB9-1 protein as the antigen and hollow nano-size silica vesicles (SV
      100) as the adjuvant. We simplified the purification method to obtain the
      partially-purified antigen VirB9-1 with a six-fold higher yield. The new
      formulations using the partially-purified VirB9-1 protein achieved higher
      antibody and cell-mediated immune responses compared to the purified ones. This
      finding suggests that the partially-purified VirB9-1 protein performs better than
      the purified ones in the vaccination against A. marginale, and a certain level of
      contaminants in the protein antigen can be self-adjuvant and boost immunogenicity
      together with the nanoparticle adjuvant. This may lead to finding a "Goldilocks"
      level of contaminants. The new nanovaccine formulation using partially-purified
      antigens along with nanoparticle adjuvants offers an alternative strategy for
      making cheaper veterinary vaccines.

PMID- 27890400
TI  - Country specific predictions of the cost-effectiveness of malaria vaccine
      RTS,S/AS01 in endemic Africa.
AB  - BACKGROUND: RTS,S/AS01 is a safe and moderately efficacious vaccine considered
      for implementation in endemic Africa. Model predictions of impact and cost
      effectiveness of this new intervention could aid in country adoption decisions.
      METHODS: The impact of RTS,S was assessed in 43 countries using an ensemble of
      models of Plasmodium falciparum epidemiology. Informed by the 32months follow-up
      data from the phase 3 trial, vaccine effectiveness was evaluated at country
      levels of malaria parasite prevalence, coverage of control interventions and
      immunization. Benefits and costs of the program incremental to routine malaria
      control were evaluated for a four dose schedule: first dose administered at six
      months, second and third - before 9months, and fourth dose at 27months of age.
      Sensitivity analyses around vaccine properties, transmission, and economic inputs
      were conducted. RESULTS: If implemented in all 43 countries the vaccine has the
      potential to avert 123 (117;129) million malaria episodes over the first 10years.
      Burden averted averages 18,413 (range of country median estimates 156-40,054)
      DALYs per 100,000 fully vaccinated children with much variation across settings
      primarily driven by differences in transmission intensity. At a price of $5 per
      dose program costs average $39.8 per fully vaccinated child with a median cost
      effectiveness ratio of $188 (range $78-$22,448) per DALY averted; the ratio is
      lower by one third - $136 (range $116-$220) - in settings where parasite
      prevalence in children aged 2-10years is at or above 10%. CONCLUSION:
      RTS,S/AS01has the potential to substantially reduce malaria burden in children
      across Africa. Conditional on assumptions on price, coverage, and vaccine
      properties, adding RTS,S to routine malaria control interventions would be highly
      cost-effective. Implementation decisions will need to further consider
      feasibility of scaling up existing control programs, and operational constraints
      in reaching children at risk with the schedule.

PMID- 27890401
TI  - Corrigendum to "Increased diffusivity in gray matter in recent onset
      schizophrenia is associated with clinical symptoms and social cognition"
      [Schizophr. Res. 176 (2-3) (Oct 2016) 144-150].

PMID- 27890402
TI  - Multi-elemental analysis of human lung samples using inductively coupled plasma
      mass spectrometry.
AB  - The aim of this study was to establish concentrations of a wide range of elements
      in human lung samples to allow better identification of potential exposures in
      subsequent cases. This study reports concentrations of 48 elements (Al, As, Au,
      B, Ba, Be, Bi, Br, Cd, Ce, Co, Cr, Cs, Cu, Fe, Ga, Gd, Ge, Hf, Hg, In, Li, Mn,
      Mo, Nb, Ni, Os, Pb, Pd, Pt, Rb, Re, Ru, Sb, Se, Sm, Sn, Sr, Ta, Te, Ti, Tl, Tm,
      V, W, Y, Zn and Zr) in fresh lung tissue samples from 54 hospital patients, of
      which 93% exhibited various forms of neoplasia. The lung samples were taken from
      unaffected, background tissue. The samples were stored as fresh tissue in
      alcohol, dried and microwave digested before analysis by inductively coupled mass
      spectrometry (ICP-MS). It was possible to establish 95th percentiles for all
      elements except for rhenium and for 40 elements mixed effects modelling was
      undertaken. Overall, the levels reported are commensurate with ranges for those
      elements that had been reported previously. The data were examined for gender,
      smoking and occupational exposures to metals. The results show that males have
      higher lung concentrations of Ni, Cr, Gd, Au and Be than females, but
      significantly lower lung concentrations of Co, Sn, W and In. Cadmium lung
      concentrations were significantly higher in smokers. Platinum lung concentrations
      were higher in those who had undergone chemotherapy and gadolinium concentrations
      were predictably high in those who had undergone imaging scans. More essential
      elements such as Cu, Br, Fe and also Ge varied the least within lung samples from
      individuals whilst Be, Hf and Pt had the greatest variances. Between individuals
      V and Li lung concentrations varied the most, whilst Cu varied least. Analysis of
      the data for those who reported as having previously worked with metals showed 24
      of the 48 elements determined were higher than those from those who had not
      reported working with metals.

PMID- 27890403
TI  - Isoelectric points and points of zero charge of metal (hydr)oxides: 50years after
      Parks' review.
AB  - The pH-dependent surface charging of metal (hydr)oxides is reviewed on the
      occasion of the 50th anniversary of the publication by G.A. Parks: "Isoelectric
      points of solid oxides, solid hydroxides, and aqueous hydroxo complex systems" in
      Chemical Reviews. The point of zero charge (PZC) and isoelectric point (IEP)
      became standard parameters to characterize metal oxides in aqueous dispersions,
      and they define adsorption (surface excess) of ions, stability against
      coagulation, rheological properties of dispersions, etc. They are commonly used
      in many branches of science including mineral processing, soil science, materials
      science, geochemistry, environmental engineering, and corrosion science. Parks
      established standard procedures and experimental conditions which are required to
      obtain reliable and reproducible values of PZC and IEP. The field is very active,
      and the number of related papers exceeds 300 a year, and the standards
      established by Parks remain still valid. Relevant experimental techniques
      improved over the years, especially the measurements of electrophoretic mobility
      became easier and more reliable, are the numerical values of PZC and IEP compiled
      by Parks were confirmed by contemporary publications with a few exceptions. The
      present paper is an up-to-date compilation of the values of PZC and IEP of metal
      oxides. Unlike in former reviews by the same author, which were more
      comprehensive, only limited number of selected results are presented and
      discussed here. On top of the results obtained by means of classical methods
      (titration and electrokinetic methods), new methods and correlations found over
      the recent 50years are presented.

PMID- 27890404
TI  - Incomplete Urethral Duplication Associated with a Dermoid Cyst in a Dog with
      Urinary Obstruction.
AB  - A 20-month-old male miniature dachshund was evaluated for a 10-week history of
      intermittent stranguria, pollakiuria, haematuria and obstructive urolithiasis.
      Retrograde urethrocystography revealed a subcutaneous saccular structure in the
      perineal area connected to the intrapelvic urethra associated with urolithiasis.
      After excision of the perineal saccular structure, microscopical examination
      confirmed the presence of transitional epithelium lining the diverticulum, with
      isolated submucosal smooth muscle bundles. This structure was attached to another
      saccular structure lined by stratified squamous keratinizing epithelium with hair
      follicles, sebaceous glands and apocrine glands. An incomplete urethral
      duplication with dermoid cyst was diagnosed. The dog recovered uneventfully from
      surgery and was still urinary continent and free from clinical signs 5 months
      after surgery. To the authors' knowledge this is the first report of an
      incomplete urethral duplication with a dermoid cyst and concurrent obstructive
      urolithiasis in a dog.

PMID- 27890405
TI  - Platelets Inhibit Migration of Canine Osteosarcoma Cells.
AB  - The interaction between platelets and tumour cells is important for tumour growth
      and metastasis. Thrombocytopenia or antiplatelet treatment negatively impact on
      cancer metastasis, demonstrating potentially important roles for platelets in
      tumour progression. To our knowledge, there is no information regarding the role
      of platelets in cancer progression in dogs. This study was designed to test
      whether canine platelets affected the migratory behaviour of three canine
      osteosarcoma cell lines and to give insights of molecular mechanisms. Intact
      platelets, platelet lysate and platelet releasate inhibited the migration of
      canine osteosarcoma cell lines. Addition of blood leucocytes to the platelet
      samples did not alter the inhibitory effect on migration. Platelet treatment also
      significantly downregulated the transcriptional levels of SNAI2 and TWIST1 genes.
      The interaction between canine platelets or molecules released during platelet
      activation and these tumour cell lines inhibits their migration, which suggests
      that canine platelets might antagonize metastasis of canine osteosarcoma. This
      effect is probably due to, at least in part, downregulation of genes related to
      epithelial-mesenchymal transition.

PMID- 27890406
TI  - Cutaneous Histiocytic Sarcoma with Regional Lymph Node Metastasis in a Netherland
      Dwarf Rabbit (Oryctolagus cuniculus).
AB  - A 10-year-old male Netherland dwarf rabbit (Oryctolagus cuniculus) was presented
      with a red nodular mass (1 cm in diameter) with ulceration and hair loss in the
      skin of the left upper lip. Cytological examination revealed atypical round
      cells. The mass was excised surgically. Histologically, the mass was composed of
      large round to polyhedral neoplastic cells with marked cytological atypia. The
      neoplastic cells were often binucleated or multinucleated. Immunohistochemically,
      the neoplastic cells were intensely positive for Iba1 and vimentin, but fewer
      neoplastic cells expressed E-cadherin. Nuclear immunoreactivity for Ki67 was
      detected in approximately 41% of the neoplastic cells. Metastasis to the left
      cervical lymph nodes was detected 6 months after the surgical excision. Based on
      clinical, histopathological and immunohistochemical findings, the present case
      was diagnosed as cutaneous histiocytic sarcoma. To the authors' knowledge
      cutaneous histiocytic disease has not been reported previously in lagomorphs.

PMID- 27890407
TI  - Postoperative Tachycardia: Clinically Meaningful or Benign Consequence of
      Orthopedic Surgery?
AB  - OBJECTIVE: To determine the clinical significance of tachycardia in the
      postoperative period. PATIENTS AND METHODS: Individuals 18 years or older
      undergoing hip and knee arthroplasty were included in the study. Two data sets
      were collected from different time periods: development data set from January 1,
      2011, through December 31, 2011, and validation data set from December 1, 2012,
      through September 1, 2014. We used the development data set to identify the
      optimal definition of tachycardia with the strongest association with the
      vascular composite outcome (pulmonary embolism and myocardial necrosis and
      infarction). The predictive value of this definition was assessed in the
      validation data set for each outcome of interest, pulmonary embolism, myocardial
      necrosis and infarction, and infection using multiple logistic regression to
      control for known risk factors. RESULTS: In 1755 patients in the development data
      set, a maximum heart rate (HR) greater than 110 beats/min was found to be the
      best cutoff as a correlate of the composite vascular outcome. Of the 4621
      patients who underwent arthroplasty in the validation data set, 40 (0.9%) had
      pulmonary embolism. The maximum HR greater than 110 beats/min had an odds ratio
      (OR) of 9.39 (95% CI, 4.67-18.87; sensitivity, 72.5%; specificity, 78.0%;
      positive predictive value, 2.8%; negative predictive value, 99.7%) for pulmonary
      embolism. Ninety-seven patients (2.1%) had myocardial necrosis (elevated
      troponin). The maximum HR greater than 110 beats/min had an OR of 4.71 (95% CI,
      3.06-7.24; sensitivity, 47.4%; specificity, 78.1%; positive predictive value,
      4.4%; negative predictive value, 98.6%) for this outcome. Thirteen (.3%) patients
      had myocardial infarction according to our predetermined definition, and the
      maximum HR greater than 110 beats/min had an OR of 1.72 (95% CI, 0.47-6.27).
      CONCLUSION: Postoperative tachycardia within the first 4 days of surgery should
      not be dismissed as a postoperative variation in HR, but may precede clinically
      significant adverse outcomes.

PMID- 27890408
TI  - MBTH: A novel approach to rapid, spectrophotometric quantitation of total algal
      carbohydrates.
AB  - A high-throughput and robust application of the 3-methyl-2-benzothiazolinone
      hydrazone (MBTH) method was developed for carbohydrate determination in
      microalgae. The traditional phenol-sulfuric acid method to quantify carbohydrates
      is strongly affected by algal biochemical components and exhibits a highly
      variable response to microalgal monosaccharides. We present a novel use of the
      MBTH method to accurately quantify carbohydrates in hydrolyzate after acid
      hydrolysis of algal biomass, without a need for neutralization. The MBTH method
      demonstrated consistent and sensitive quantitation of algae-specific
      monosaccharides down to 5 MUg mL-1 without interference from other algae acidic
      hydrolyzate components.

PMID- 27890409
TI  - Geochemistry of arsenic in low sulfide-high carbonate coal waste rock, Elk
      Valley, British Columbia, Canada.
AB  - This study investigated the geochemistry of arsenic (As) in low sulfide-high
      carbonate coal waste rock of the Elk Valley, British Columbia, Canada. Its
      abundance and mineralogical associations in waste rock of different placement
      periods were determined in addition to its mobilization into porewater and rock
      drain effluent. The mean (5.34mg/kg; 95% confidence interval: 4.95-5.73mg/kg) As
      concentration in the waste rock was typical of sedimentary rock. Electron
      microprobe and As K-edge X-ray absorption near-edge spectroscopic analyses showed
      the As is predominantly associated with primary pyrites in both source and
      freshly blasted waste rock. However, in aged waste rock the As is associated with
      both primary pyrites and secondary Fe oxyhydroxides. Oxidation of pyrite in waste
      rock dumps was reflected by the presence of high concentrations of SO42- in
      porewater and oxidation rims of Fe oxyhydroxides around pyrite grains. Acid
      released from pyrite oxidation to Fe oxyhydroxides is neutralized by carbonate
      mineral dissolution that buffers the pH in the waste rock to circumneutral
      values. Adsorption of As onto secondary Fe oxyhydroxides provides an internal
      geochemical control on As release during pyrite oxidation and porewater flushing
      from the dump, resulting in the low As concentrations observed in porewater
      (median: 9.91MUg/L) and rock-drain effluent (median: 0.31MUg/L). Secondary Fe
      oxyhydroxides act as a long-term sink for As under present day hydrologic
      settings in waste rock dumps in the Elk Valley.

PMID- 27890410
TI  - Extraction techniques using isopropanol and Tenax to characterize polycyclic
      aromatic hydrocarbons bioavailability in sediment.
AB  - Polycyclic aromatic hydrocarbon (PAH)-degrading bacterium strain J1-q
      (Sphingomonas pseudosanguinis strain J1-q) was isolated from Yangtze River
      surface sediment in the downtown area of Chongqing in a previous study.
      Isopropanol and Tenax extraction techniques were used to characterize the
      bioavailability of target PAH compounds. Phenanthrene (Phe) and fluoranthene
      (Fluo) were the target PAHs due to their significant background concentrations in
      surface sediment samples. Isopropanol solutions at concentrations of 50-100% and
      residual Phe and Fluo concentrations in sediment were correlated, with R2 values
      of 0.9846 and 0.9649, respectively. The quantities of the Phe and Fluo fractions
      extracted for 3days with isopropanol from sediment were closely related with the
      corresponding quantities of PAHs degraded by bacterial strain J1-q when the
      extracting concentrations were 55% and 80%, respectively. The quantity of Phe
      extracted by Tenax agreed with the total quantity biodegraded when the Tenax:
      sediment mass ratio was 0.25 and the target PAHs were degraded for 30d, whereas
      the extracted quantity of Fluo accounted for 93.30% of the total quantity
      biodegraded by the bacterium. The triphasic model was appropriate to simulate the
      consecutive Phe and Fluo extraction process using Tenax at various Tenax:
      sediment ratios, and all simulated correlation coefficients were >0.9151. A 24-h
      extraction period was adequate to estimate the rapidly desorbing fractions when
      they were extracted with Tenax. Isopropanol extraction was preferable to
      characterize Phe and Fluo bioavailability under the experimental conditions,
      whereas Tenax extraction was useful to predict bioavailability of the two target
      PAHs with particular selectivity.

PMID- 27890411
TI  - Effect of hydrolysis of N2O5 on nitrate and ammonium formation in Beijing China:
      WRF-Chem model simulation.
AB  - Beijing, the capital of China, is a mega city with a population of >20 million.
      In recent years, the city has experienced heavy air pollution, with particulate
      matter (PM) being one of its top pollutants. In the last decade, extensive
      efforts have been made to characterize the sources, properties, and processes of
      PM in Beijing. Despite progress made by previous studies, there are still some
      important questions to be answered and addressed. The focus of this research is
      to study the impact of the heterogeneous hydrolysis of N2O5 on the formation of
      nitrate (NO3-) and ammonium (NH4+) in Beijing. The results show that during heavy
      pollution days (e.g., during 14-17 September 2015, with PM2.5 concentration over
      100MUg/m3), the concentrations of NO2 and O3 were high, with maxima of 90 and
      240MUg/m3, respectively, providing high precursors for the formation of N2O5. In
      addition, the aerosol and sulfate concentrations were also high, with maxima of
      201MUg/m3 and 23MUg/m3 respectively, providing reacting surface for the
      heterogeneous reaction. As a result, the hydrolysis of N2O5 led to 21.0%
      enhancement of nitrate (NO3-) and 7.5% enhancement of ammonium (NH4+). It is
      worth to note that this important effect only occurred in high pollution days
      (PM2.5 concentration over 100MUg/m3). During low-pollution periods (PM2.5
      concentration <100MUg/m3), the effect of hydrolysis of N2O5 on the formation of
      nitrate and ammonium was insignificant (variation rate <5%). This study suggests
      that during heavy pollution periods, the hydrolysis of N2O5 enhances the level of
      aerosol pollution in Beijing, and needs to be further studied in order to perform
      efficient air pollution control and mitigation strategies.

PMID- 27890412
TI  - Spatial distributions of beta-cyclocitral and beta-ionone in the sediment and
      overlying water of the west shore of Taihu Lake.
AB  - After large-scale outbreaks of algal blooms in eutrophic water, considerable
      amounts of algae residue accumulate in near-shore zones before fermenting rapidly
      and becoming malodorous. Taste and odor pollution caused by secondary metabolites
      from cyanobacterial blooms has become a serious and widespread environmental
      problem. Two typical odorous compounds, beta-cyclocitral and beta-ionone, have
      gained increasing attention in recent years. In this paper, the spatial
      distributions of beta-cyclocitral and beta-ionone in the sediments and overlying
      water off the west shore of Taihu Lake were investigated. The results showed that
      beta-cyclocitral, beta-ionone and nutrients are released during the degradation
      of fresh cyanobacteria, especially in the early stages. The odorous compounds and
      nutrients greatly decreased as the depth of sediment increased, indicating that
      reed roots can absorb beta-cyclocitral, beta-ionone and nutrients. Furthermore,
      removing cyanobacteria and dredging sludge might reduce the release of beta
      cyclocitral and beta-ionone.

PMID- 27890413
TI  - Hydrological and depositional processes associated with recent glacier recession
      in Yanamarey catchment, Cordillera Blanca (Peru).
AB  - In this study, we investigate changes in the glaciated surface and the formation
      of lakes in the headwater of the Querococha watershed in Cordillera Blanca (Peru)
      using 24 Landsat images from 1975 to 2014. Information of glacier retreat was
      integrated with available climate data, the first survey of recent depositional
      dynamics in proglacial Yanamarey Lake (4600m a.s.l.), and a relatively short
      hydrological record (2002-2014) at the outlet of Yanamarey Lake. A statistically
      significant temperature warming (0.21 degrees C decade-1 for mean annual
      temperature) has been detected in the region, and it caused a reduction of the
      glacierized area since 1975 from 3.5 to 1.4km-2. New small lakes formed in the
      deglaciated areas, increasing the flooded area from1.8ha in 1976 to 2.8ha in
      2014. A positive correlation between annual rates of glacier recession and runoff
      was found. Sediment cores revealed a high sedimentation rate (>1cmyr-1) and two
      contrasted facies, suggesting a shift toward a reduction of meltwater inputs and
      higher hydrological variability likely due to an increasing role of precipitation
      on runoff during the last decades. Despite the age control uncertainties, the
      main transition likely occurred around 1998-2000, correlating with the end of the
      phase with maximum warming rates and glacier retreat during the 1980s and 1990s,
      and the slowing down of expansion of surface lake-covered surface. With this
      hydrological - paleolimnological approach we have documented the association
      between recent climate variability and glacier recession and the rapid transfer
      of hydroclimate signal to depositional and geochemical processes in high
      elevation Andean environments. This, study also alerts about water quality risks
      as proglacial lakes act as secondary reservoirs that trap trace and minor
      elements in high altitude basins.

PMID- 27890414
TI  - Developmental neurotoxicants in human milk: Comparison of levels and intakes in
      three European countries.
AB  - Developmental neurotoxicants (DNTs), such as methylmercury (MeHg),
      polychlorinated biphenyls (PCBs) and selected organochlorine pesticides (OCPs),
      have gained increasing interest recently due to their possible relation to
      developmental disorders in children, which are increasing worldwide. We analyzed
      levels of 14 developmental neurotoxicants in human milk samples from Slovakia
      (n=37), the Netherlands (n=120) and Norway (n=388). Positive identification for
      most target analytes was >95% in all samples. In all three countries MeHg was
      measured for the first time in mother milk. The highest MeHg levels were observed
      in Norway (39pgg-1 ww) with the highest fish consumption. Levels of indicator
      PCBs (iPCBs, sum of PCB 28, 52, 101, 138, 153 and 180), HCB and DDE+DDT were 2-4
      times higher in Slovakia compared to the Netherlands or Norway. The levels of
      MeHg and organochlorine compounds were used for calculations of weekly or daily
      intakes (top-down approach) by means of pharmacokinetic modeling. The intakes
      ranged from 0.014 to 0.142MUgkgbw-1week-1 for MeHg and from 0.043 to 17.4ngkgbw
      1day-1 for organochlorine compounds in all three countries. Intakes of iPCBs
      exceeded a tolerable daily intake of 10ngkgbw-1day-1 in 16% of the Slovak
      participants. The top-down estimates were compared with bottom-up intakes based
      on national dietary estimates and the results showed good consistency between
      both approaches, with the bottom-up intakes exceeding the top-down by a factor of
      maximum 3.8 for iPCBs in the Netherlands and 3.9 for HCB in Slovakia. This
      confirms that food consumption in all three countries represents the dominant
      pathway of exposure to these developmental neurotoxicants.

PMID- 27890415
TI  - Removing ammonium from water using modified corncob-biochar.
AB  - Ammonium pollution in groundwater and surface water is of major concern in many
      parts of the world due to the danger it poses to the environment and people's
      health. This study focuses on the development of a low cost adsorbent,
      specifically a modified biochar prepared from corncob. Evaluated here is the
      efficiency of this new material for removing ammonium from synthetic water
      (ammonium concentration from 10 to 100mg/L). The characteristics of the modified
      biochar were determined by Brunauer-Emmett-Teller (BET) test, Fourier transform
      infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM). It was found
      that ammonium adsorption on modified biochar strongly depended on pH. Adsorption
      kinetics of NH4+-N using modified biochar followed the pseudo-second order
      kinetic model. Both Langmuir and Sips adsorption isotherm models could simulate
      well the adsorption behavior of ammonium on modificated biochar. The highest
      adsorption capacity of 22.6mg NH4+-N/g modified biochar was obtained when the
      biochar was modified by soaking it in HNO3 6M and NaOH 0.3M for 8h and 24h,
      respectively. The high adsorption capacity of the modified biochar suggested that
      it is a promising adsorbent for NH4+-N remediation from water.

PMID- 27890416
TI  - Larix decidua delta18O tree-ring cellulose mainly reflects the isotopic signature
      of winter snow in a high-altitude glacial valley of the European Alps.
AB  - We analyzed the chronologies of cellulose stable isotopes (delta13C and delta18O)
      and tree-ring widths from European larch (Larix decidua) in a high-altitude site
      (2190ma.s.l.) at the bottom of a glacial valley in the Italian Alps, and
      investigated their dependence on monthly meteorological variables and delta18O
      precipitation values. The delta18O of tree-ring cellulose appears to be strongly
      driven by the delta18O of winter snowfall (November to March), which suggests
      that larch trees mostly use the snow-melt water of the previous winter during the
      growing season. This water, which also comes from the slope streams and from the
      underground flow of nearby steep slopes, infiltrates the soil in the valley
      bottom. The tree-ring cellulose delta18O values were also found to be influenced
      by the August precipitation delta18O and mean temperature. The associated
      regression model shows that the delta18O chronology from the tree rings explains
      up to 34% of the variance in the winter precipitation delta18O record,
      demonstrating the potential for reconstructing the delta18O isotopic composition
      of past winter precipitation in the study region. Unlike most other tree-ring
      studies that focus on growing season signals, in our study the summer signal was
      small and the winter signal dominant due to the special conditions of the glacial
      valley. Site topography, geomorphology and soil characteristics in particular
      influence the stable isotope signal in tree-ring cellulose.

PMID- 27890417
TI  - Mycobacterium fortuitum empyema associated with an indwelling pleural catheter:
      Case report and review of the literature.
AB  - Mycobacterium fortuitum is a rapidly growing mycobacterium (RGM) that is an
      uncommon cause of healthcare-associated infections. The most common infections
      caused by M. fortuitum include skin, soft tissue, and catheter-related
      infections. Although occasionally cultured from sputum samples, M. fortuitum is a
      rare cause of pulmonary disease. We report a case of M. fortuitum empyema
      associated with an infected pleural catheter and review M. fortuitum pulmonary
      infections.

PMID- 27890418
TI  - Comparative in vitro activity of oritavancin and other agents against methicillin
      susceptible and methicillin-resistant Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a threat
      to the public health due to their prevalence and associated mortality and
      morbidity. Several agents have been recently approved to treat MRSA skin
      infections including lipoglycopeptides (dalbavancin, oritavancin, and
      telavancin), ceftaroline, and tedizolid. This study compared the MIC, minimum
      bactericidal concentration (MBC), and time-kill of these agents alongside
      daptomycin, linezolid, and vancomycin against MRSA (n=15); meropenem, cefazolin,
      and nafcillin were also included against methicillin-susceptible S. aureus (MSSA
      [n=12]). MIC and MBC testing was conducted in accordance with Clinical and
      Laboratory Standards Institute guidelines, and time-kills were evaluated at
      multiples of the MIC and the free-drug maximum plasma concentration (fCmax) at
      both standard and high inoculum densities for a subset of MRSA (n=2) and MSSA
      (n=2). MRSA and MSSA were highly susceptible to all agents, with the
      lipoglycopeptides having the most potent activity by MIC50/90. All agents
      excluding tedizolid and linezolid were bactericidal by MBC for MRSA and MSSA,
      though dalbavancin and telavancin exhibited strain-specific bactericidal activity
      for MRSA. All agents excluding tedizolid and linezolid were bactericidal by time
      kill at their respective fCmax against MRSA and MSSA at standard inoculum
      density, though oritavancin exhibited the most rapid bactericidal activity.
      Oritavancin and daptomycin at their respective fCmax maintained similar kill
      curves at high inoculum density. In contrast, the killing observed with other
      agents was typically reduced or slowed at high inoculum density. These data
      demonstrate the rapid bactericidal activity of oritavancin and daptomycin against
      S. aureus relative to other MRSA agents regardless of bacterial burden.

PMID- 27890419
TI  - In vitro activity of tigecycline alone and antimicrobial combinations against
      clinical Neisseria gonorrhoeae isolates.
AB  - In this study, we determined the in vitro activity of various combinations of
      antimicrobial agents against 54 Neisseria gonorrhoeae isolates. The combined
      activity of ceftriaxone (CRO) and azithromycin (AZM), CRO and doxycycline (DOX),
      CRO and spectinomycin (SPT), cefixime (CFX) and AZM, CFX and DOX, and CFX and SPT
      was determined using a checkerboard method. The fractional inhibitory
      concentration index (FICI) values for all combinations were either additive or
      indifferent, and no synergistic or antagonistic effects were found. The FICI
      comparison in each combination did not show any difference according to the
      N.gonorrhoeae-resistant phenotypes and genotypic characteristics, including
      penicillinase-producing N. gonorrhoeae, tetracycline-resistant N. gonorrhoeae,
      stratified MIC of all antibiotics, and N. gonorrhoeae multiantigen sequence
      typing. MIC50 and MIC90 of tigecycline by agar dilution were 0.5 mg/L and 0.5
      mg/L, respectively, which were lower than that of tetracycline and DOX.
      Additive/indifference results could suggest that combinations that include CRO
      may be used safely without a significant likelihood of generating resistance.

PMID- 27890420
TI  - Blow, winds, and crack your cheeks!

PMID- 27890421
TI  - Contrast-enhanced MDCT in patients with pancreatic neuroendocrine tumours:
      correlation with histological findings and diagnostic performance in
      differentiation between tumour grades.
AB  - AIM: To identify the multidetector computed tomography (MDCT) features of
      pancreatic neuroendocrine tumours (pNETs), which correlate with tumour histology
      and enable preoperative grading. MATERIALS AND METHODS: Thirty-nine patients with
      histologically confirmed pNET who underwent preoperative contrast-enhanced MDCT
      were included in this study. Nineteen tumours were classified as Grade 1 (G1) and
      20 as Grade 2 (G2). Histopathology slides were reviewed to assess the
      intratumoural microvascular density (MVD) and the amount of tumour stroma.
      Computed tomography (CT) image analysis included tumour size, margin delineation,
      calcifications, homogeneity, contrast enhancement (CE) pattern, tumour absolute
      and relative enhancement, presence of cystic changes, pancreatic duct dilatation,
      regional and distant metastases. The diagnostic ability to predict tumour grade
      was measured for each MDCT finding and their combinations. RESULTS: The mean
      arterial enhancement ratio had a mean+/-standard deviation of 1.53+/-0.45 in G1
      and 1.01+/-0.33 in G2 pNETs (p=0.0003) and correlated with intratumoural
      microvascular density (MVD; r=0.55, p=0.0002). Tissue stroma percentage did not
      correlate with imaging findings. Late CE of the tumour (the peak attenuation
      observed in the venous phase) was significantly associated with G2. Tumour size
      >20 mm, arterial enhancement ratio <1.1, and late CE showed 74.4%, 79.5%, and
      74.4% accuracy, respectively, in diagnosing G2 tumours, while the accuracy of at
      least two of these criteria used in combination was 82%. Based on these results,
      a diagnostic algorithm was proposed, which showed high interobserver agreement
      (k=0.82) in the prediction of tumour grade. CONCLUSION: Contrast-enhanced MDCT
      features correlate with histological findings and enable the differentiation
      between G1 and G2 pNETs during preoperative examination.

PMID- 27890422
TI  - Treatment efficacy of CT-guided percutaneous microwave ablation for primary
      hepatocellular carcinoma.
AB  - AIM: To evaluate the treatment efficacy and potential complications of computed
      tomography (CT)-guided microwave ablation for primary hepatocellular carcinoma
      (HCC). MATERIALS AND METHODS: Data were collected and analysed from 220 HCC
      patients treated with CT-guided microwave ablation and followed up for 2 years.
      Independent risk factors for overall survival and progression-free survival (PFS)
      were analysed. RESULTS: Among all cases followed, the cumulative overall survival
      rates at 1 and 2 years were 95.45% and 89.09%. The cumulative 1- and 2-year PFS
      rates were 80.90% and 62.73%. For patients with Barcelona Clinic Liver Cancer
      (BCLC) class C (n=60), the cumulative 1- and 2-year overall survival rates were
      89.09% and 74.54%. In this group, patients with tumour invasion of blood vessels
      or tumour-related symptoms suffered a worse overall survival compared to those
      without (p=0.011). No fatal complications were observed. Child-Pugh score
      (p=0.030) and BCLC class (p=0.012) were independent risk factors for overall
      survival. The number of tumour nodules was an independent risk factor for
      reoccurrence. CONCLUSION: CT-guided percutaneous microwave ablation could be an
      effective and safe treatment option for HCC patients.

PMID- 27890423
TI  - Hepatic epithelioid angiomyolipoma: clinical features and imaging findings of
      contrast-enhanced ultrasound and CT.
AB  - AIM: To evaluate the clinical features and imaging findings of epithelioid
      angiomyolipoma (EAML) on contrast-enhanced ultrasound (CEUS) and contrast
      enhanced computed tomography (CECT). MATERIALS AND METHODS: During January 2006
      to November 2015, six patients with histopathologically proven hepatic EAML were
      evaluated using both CECT and ultrasonography. Six patients underwent CEUS and
      four patients had CECT images. Patients' demographics, clinical presentations,
      laboratory test results, and imaging appearances were collected and analysed.
      RESULTS: Six patients were female, and the mean age was 43.5 years. All hepatic
      EAMLs were solitary. None of patients had specific symptoms, and laboratory tests
      were normal in all patients. The maximal diameter of the lesions ranged from 3.1
      to 6.5 cm (mean 4.4 cm). Baseline ultrasound revealed that 50% of hepatic EAMLs
      were hypo-echoic and 50% were mixed echoic. CEUS showed that 100% of the hepatic
      EAMLs displayed homogeneous hyperenhancement in the arterial phase and 67% (4/6)
      showed hypo-enhancement in the late phase. On CECT, 100% (4/4) of the neoplasms
      were significantly hyperenhanced in the arterial phase and washout in the portal
      phase. There was no recurrence or metastasis after a mean follow-up period of
      11.8 months. CONCLUSION: Hepatic EAML shows similar enhancement patterns to that
      of hepatocellular carcinoma. It should be considered as a possible differential
      diagnosis in female patients without viral hepatitis infection.

PMID- 27890424
TI  - Recent scenario of microRNA as diagnostic and prognostic biomarkers of prostate
      cancer.
AB  - Prostate cancer (CaP) is a leading cause of cancer death and displays a broad
      range of clinical behavior from relatively indolent to aggressive metastatic
      disease. Due to the alteration and incomplete characterization of the CaP genomic
      markers, the quest for novel cellular metabolic regulatory molecules like micro
      RNA (miRNA) as a biomarker could be considered for the prognosis and treatment of
      CaP in future. In this article, we review the existing literature pertaining to
      CaP. Study provides a comprehensive miRNA profile expressed in CaP. Beside the
      miRNA expressed in the tumor tissue, circulating miRNAs have been found highly
      stable and are both detectable and quantifiable in a range of accessible bio
      fluids; therefore, miRNA has the potential to be useful diagnostic, prognostic
      and predictive biomarker. Along with being an important molecule in modulation of
      CaP progression, the miRNA have certain limitations such as lack of stable
      expression of multiple target genes and often disrupt entire signaling networks
      of cellular metabolic pathways. We conclude that: The alteration of miRNA and
      their role played in cellular regulatory networks would be the next target of
      basic research in CaP. The miRNAs identified may be validated and modeled to
      understand their role in CaP, using bioinformatics. There is an immediate unmet
      need in the translational approach of identified miRNAs. The characterization of
      miRNAs involved in CaP is still incomplete: adequate validation studies are
      required to corroborate current results.

PMID- 27890425
TI  - The changing landscape in radiotherapy for breast cancer: Lessons from long term
      follow-up in some European breast cancer trials.
AB  - This review describes the developments in the radiation treatment of breast
      cancer based on some randomized European trials during the past decades. It will
      focus on the relevance of long term follow-up in breast cancer patients, starting
      with the surprising and important change in treatment results during follow-up
      shown in a locally advanced breast cancer trial. Breast conserving therapy (BCT)
      in stage I and II breast cancer was explored and tested in a randomized trial to
      prove equivalence between BCT and mastectomy. The positive outcome led to trials
      in breast conserving therapy with lower doses and partial breast irradiation.
      Finally the need for finding genetic profiles for predicting treatment response
      will be addressed in a trial with preoperative partial breast irradiation.

PMID- 27890426
TI  - Patient-reported quality of life after stereotactic body radiation therapy versus
      moderate hypofractionation for clinically localized prostate cancer.
AB  - BACKGROUND AND PURPOSE: Evaluate changes in bowel, urinary and sexual patient
      reported quality of life following treatment with moderately hypofractionated
      radiotherapy (<5Gray/fraction) or stereotactic body radiation therapy (SBRT;5
      10Gray/fraction) for prostate cancer. MATERIALS AND METHODS: In a pooled multi
      institutional analysis of men treated with moderate hypofractionation or SBRT, we
      compared minimally detectable difference in bowel, urinary and sexual quality of
      life at 1 and 2years using chi-squared analysis and logistic regression. RESULTS:
      378 men received moderate hypofractionation compared to 534 men who received
      SBRT. After 1year, patients receiving moderate hypofractionation were more likely
      to experience worsening in bowel symptoms (39.5%) compared to SBRT (32.5%;
      p=.06), with a larger difference at 2years (37.4% versus 25.3%, p=.002).
      Similarly, patients receiving moderate fractionation had worsening urinary
      symptom score compared to patients who underwent SBRT at 1 and 2years (34.7%
      versus 23.1%, p<.001; and 32.8% versus 14.0%, p<.001). There was no difference in
      sexual symptom score at 1 or 2years. After adjusting for age and cancer
      characteristics, patients receiving SBRT were less likely to experience worsening
      urinary symptom scores at 2years (odds ratio: 0.24[95%CI: 0.07-0.79]).
      CONCLUSIONS: Patients who received SBRT or moderate hypofractionation have
      similar patient-reported change in bowel and sexual symptoms, although there was
      worse change in urinary symptoms for patients receiving moderate
      hypofractionation.

PMID- 27890428
TI  - Vancomycin-Resistant Enterococcus Colonization and Bacteremia and Hematopoietic
      Stem Cell Transplantation Outcomes.
AB  - The association between pre-hematopoietic stem cell transplantation (HSCT)
      vancomycin-resistant Enterococcus (VRE) colonization, HSCT-associated VRE
      bacteremia, and HSCT mortality is disputed. We studied 161 consecutive patients
      with acute leukemia who underwent HSCT at our hospital between 2006 and 2014, of
      whom 109 also received leukemia induction/consolidation on our unit. All
      inpatients had weekly VRE stool surveillance. Pre-HSCT colonization was not
      associated with increases in HSCT mortality but did identify a subgroup of HSCT
      recipients with a higher risk for VRE bacteremia and possibly bacteremia from
      other organisms. The major risk factor for pre-HSCT colonization was the number
      of hospital inpatient days between initial admission for leukemia and HSCT. One
      third of evaluable patients colonized before HSCT were VRE-culture negative on
      admission for HSCT; these patients had an increased risk for subsequent VRE stool
      surveillance positivity but not VRE bacteremia. Molecular typing of VRE isolates
      obtained before and after HSCT showed that VRE strains frequently change.
      Postengraftment VRE bacteremia was associated with a much higher mortality than
      pre-engraftment VRE bacteremia. Pre-engraftment bacteremia from any organism was
      associated with an alternative donor and resulted in an increase in hospital
      length of stay and cost. Mortality was similar for pre-engraftment VRE bacteremia
      and pre-engraftment bacteremia due to other organisms, but mortality associated
      with post-engraftment VRE bacteremia was higher and largely explained by
      associated severe graft-versus-host disease and relapsed leukemia. These data
      emphasize the importance of distinguishing between VRE colonization before HSCT
      and at HSCT, between pre-engraftment and postengraftment VRE bacteremia, and
      between VRE bacteremia and bacteremia from other organisms.

PMID- 27890427
TI  - Internal and external generalizability of temporal dose-response relationships
      for xerostomia following IMRT for head and neck cancer.
AB  - BACKGROUND AND PURPOSE: To study internal and external generalizability of
      temporal dose-response relationships for xerostomia after intensity-modulated
      radiotherapy (IMRT) for head and neck cancer, and to investigate potential
      amendments of the QUANTEC guidelines. MATERIAL AND METHODS: Objective xerostomia
      was assessed in 121 patients (nCohort1=55; nCohort2=66) treated to 70Gy@2Gy in
      2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap
      populations) were conducted in Cohort1, and generalizability of the best
      performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and
      Hosmer-Lemeshow p-values (pHL)). Ultimately and for clinical guidance, minimum
      mean dose thresholds to the contralateral and the ipsilateral parotid glands
      (Dmeancontra, Dmeanipsi) were estimated from the generated dose-response curves.
      RESULTS: The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11
      12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher
      Dmeancontra and Dmeanipsi (Cohort1: 0.17.Dmeancontra+0.11.Dmeanipsi-8.13;
      AUC=0.90+/-0.05; p=0.0002+/-0.002; pHL=0.22+/-0.23; Cohort2: AUC=0.81; p<0.0001;
      pHL=0.27). The identified minimum Dmeancontra thresholds were lower than in the
      QUANTEC guidelines (Cohort1/Cohort2: Dmeancontra=12/19Gy; Dmeancontra,
      Dmeanipsi=16, 25/20, 26Gy). CONCLUSIONS: Increased Dmeancontra and Dmeanipsi
      explain short-term xerostomia following IMRT. Our results also suggest decreasing
      Dmeancontra to below 20Gy, while keeping Dmeanipsi to around 25Gy. Long-term
      xerostomia was less frequent, and no dose-response relationship was established
      for this follow-up time.

PMID- 27890429
TI  - Knockdown of HIPK2 attenuates the pro-fibrogenic response of hepatic stellate
      cells induced by TGF-beta1.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2), a member of HIPKs family, is
      considered as a key regulator in fibrosis. However, the roles of HIPK2 in hepatic
      stellate cells (HSCs) activation and liver fibrosis are still unclear. Therefore,
      in this study, we investigated the roles of HIPK2 in HSCs activation and liver
      fibrosis. Our results showed that HIPK2 expression was significantly up-regulated
      in liver fibrotic tissues and TGF-beta1-treated HSCs. Knockdown of HIPK2
      significantly inhibited TGF-beta1-induced HSCs proliferation, as well as
      decreased the expression levels of alpha-SMA and collagen I. Furthermore,
      knockdown of HIPK2 attenuated the phosphorylation of Smad3 in the presence of TGF
      beta1. In conclusion, these results demonstrated that HIPK2 may function as a
      novel regulator to modulate HSC activation, potentially by inhibiting the TGF
      beta1/Smad3 signaling pathway. The results provide supporting evidence that HIPK2
      may be a potential target for the treatment of liver fibrosis.

PMID- 27890430
TI  - TAR DNA-binding protein 43 inhibits inflammatory response and protects
      chondrocyte function by modulating RACK1 expression in osteoarthritis.
AB  - BACKGROUND: TAR DNA-binding protein-43 (TDP-43, transactive response DNA binding
      protein 43kDa) accumulates in the cytoplasm of affected neurons and glia, as
      large inclusions of stress granules (SGs). However, the mechanism of TDP-43
      interaction with the target genes and its specific role in osteoarthritis (OA)
      progression is still unknown. The goal of this study was to identify the role of
      TDP-43 in OA progression by modulating its target genes. METHODS: MSCs were
      transfected with TDP-43 gene lentivirus. The role of elevated TDP-43 expression
      in the differentiation of MSCs to chondrocytes was investigated. Cell function
      assay was used to evaluate the proliferation and apoptosis of Human chondrocytes
      (HCs) co-cultured with MSC. Truncated TDP-43/p35 expression and SGs formation in
      HCs were identified using cyto-immunofluorescence assay. Critical genes mediating
      apoptotic and proliferative signaling in HCs were measured using co-culturing MSC
      assays. The phosphorylation of key kinases was analyzed using the HTRF
      phosphokinase assay, and the expression of key genes in proliferative and
      apoptotic signaling transduction pathways was detected using qRT-PCR. RESULTS:
      The MSCs differentiated into HCs after transfection of TDP-43 genes. The TDP-43
      can degrade truncated TDP-43/p35, and promote SGs formation and HCs
      proliferation, and inhibit HCs apoptosis after co-culturing with MSCs. TDP-43
      overexpression in MSCs promoted high expression of RACK1 and promoted
      phosphorylation of key kinases in HCs. Critical genes were highly expressed in
      P38 MAPK/MKK3 proliferative signaling, but not in P38 MAPK/JNK MAPK signaling.
      CONCLUSIONS: The chondrogenically differentiation of MSCs was not influenced by
      transfection of TDP-43 genes, and promoted HCs growth after co-culturing with
      HCs. The data indicated that TDP-43/p35 contributed to SGs formation by promoting
      RACK1 expression. The study sheds new light on post-transcriptional regulation
      and apoptosis in OA by RACK1, which is a potential treatment strategy for OA.

PMID- 27890431
TI  - Neuroprotective mechanisms of plant extracts against MPTP induced neurotoxicity:
      Future applications in Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease
      after Alzheimer's disease, affecting about seven to 10 million patients
      worldwide. The major pathological features of PD are loss of dopaminergic neurons
      in the nigrostriatal pathway and accumulation of alpha-synuclein molecules,
      forming Lewy bodies. Until now, there is no effective cure for PD, and
      investigators are searching for neuroprotective strategies to stop or slow the
      disease progression. The MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
      induced neurotoxicity of the nigrostriatal pathway has been used to initiate PD
      in animal models. Multiple experimental studies showed the ability of several
      plant extracts to protect against MPTP induced neurotoxicity through activation
      of catalase, superoxide dismutase, and glutathione reductase enzymes, which
      reduce the cellular concentration of free radicals, preventing intracellular Ca++
      release and subsequent apoptosis signaling. Other neuroprotective mechanisms of
      plant extracts include promoting autophagy of alpha-synuclein molecules and
      exerting an antiapoptotic activity via inhibition of proteolytic poly (ADP
      ribose) polymerase and preventing caspase cleavage. The variety of
      neuroprotective mechanisms of natural plant extracts may allow researchers to
      target PD progression in different pathological stages and may be through
      multiple pathways. Further investigations are required to translate these
      neuroprotective mechanisms into safe and effective treatments for PD.

PMID- 27890432
TI  - Silencing of long non-coding RNA SBDSP1 suppresses tumor growth and invasion in
      colorectal cancer.
AB  - Long non-coding RNAs (lncRNAs) play critical roles in tumor development and
      progression. This study was undertaken to examine the expression and biological
      functions of a novel lncRNA SBDSP1 in colorectal cancer (CRC). Quantitative real
      time PCR analysis was used to measure the expression of SBDSP1 in CRC tissues and
      cell lines. Knockdown of SBDSP1 via short hairpin RNA technology was performed to
      determine the roles of SBDSP1 in CRC cell growth, colony formation, cell cycle
      progression, migration, and invasion. The effect of SBDSP1 knockdown on
      tumorigenesis of CRC cells was investigated in a subcutaneous tumor mouse model.
      Western blot analysis was done to examine the involvement of signaling pathways
      in the action of SBDSP1. Notably, SBDSP1 was overexpressed in CRC tissues and
      cells relative to corresponding normal controls. Moreover, SBDSP1 expression was
      significantly greater in CRCs with nodal metastasis than in primary tumors
      (P=0.0259). Downregulation of SBDSP1 significantly inhibited cell proliferation,
      colony formation, migration, and invasion in SW480 and HCT116 cells, which was
      accompanied by suppression of Akt, ERK1/2, and STAT3 phosphorylation. SBDSP1
      depleted cells showed a G0/G1 cell cycle arrest and deregulation of p21 and
      cyclin D1. In vivo studies confirmed that SBDSP1 downregulation retarded the
      growth of HCT116 xenogaft tumors. Altogether, SBDSP1 plays an essential role in
      CRC cell growth, invasion, and tumorigenesis, largely through inactivation of
      multiple signaling pathways. Therefore, targeting SBDSP1 may have therapeutic
      benefits in the treatment of CRC.

PMID- 27890433
TI  - Levels of vitamin C In the blood plasma patients treated with coronary artery
      bypass grafting increases significantly after surgery.
AB  - One strong risk factor of coronary artery disease (CAD), which affects the levels
      of vitamin C in the blood is cigarette smoking. The supplementary effects of
      coronary artery bypass grafting (CABG) is smoking cessation by patients.
      Therefore, the aim of this study was to examine the level of vitamin C in the
      blood plasma one day before and one month after CABG. Human blood were collected
      from 20 patients (men); 1day before and 1 month after CABG. All patients were
      smoker and after CABG they declared their not smoking. The concentration of
      vitamin C in the blood plasma was assayed by FIA method with spectrophotometric
      detection. The mean value of the vitamin C concentration 1day before CABG was
      12.36+/-2.84MUmol/L (mean+/-SD), 1 month after CABG 40.07+/-10.95MUmol/L (mean+/
      SD). The average increase in the concentration of vitamin C was 3.27+/-0.73 times
      (mean+/-SD) and showed significant positive correlations (Pearson r=0.657,
      p=0.002). It should be consider incorporating the recommendations of preoperative
      smoking cessation for at least one month prior to CABG and/or additional
      supplementation. In addition it would be relevant to monitor the level of vitamin
      C in the patients' blood in the preoperative period.

PMID- 27890434
TI  - miR-98 inhibits hepatocellular carcinoma cell proliferation via targeting EZH2
      and suppressing Wnt/beta-catenin signaling pathway.
AB  - Hepatocellular carcinoma (HCC) is a highly aggressive solid malignancy in the
      word. Aberrant microRNA (miRNA) expression is involved in human diseases
      including cancer. In the current study, we explore the function of miR-98 in HCC
      cell proliferation. We found that expression level of miR-98 was significantly
      decreased in HCC tissues and cells lines compared with adjacent non-tumor issues
      and human hepatic cell line LO2. Increased expression of miR-98 suppressed HCC
      cell proliferation and arrested HCC cell cycle in G0/G1 phase. While, suppressed
      expression of miR-98 showed the opposite effect. Bioinformatics analysis revealed
      EZH2, a putative tumor promoter as a potential target of miR-98. Additionally,
      luciferase reporter assay revealed that miR-98 directly binds to the 3'
      untranslated region (3'-UTR) of EZH2 mRNA. Furthermore, we demonstrated that miR
      98 could reduce the Wnt/beta-catenin signal pathway by suppressing EZH2 directly.
      Moreover, inhibition of EZH2 abrogated the effect of miR-98 inhibitor on HCC cell
      proliferation. Taken together, these results suggested that miR-98 functioned as
      a potential tumor suppressor by regulating Wnt/beta-catenin signal pathway
      through direct suppression of EZH2 expression and might sever as a potential
      therapeutic target for HCC patients.

PMID- 27890435
TI  - Treating Hypoalbuminemia.
AB  - Hypoalbuminemia is common and associated with a variety of disease processes,
      including those leading to systemic inflammatory response syndrome,
      gastrointestinal disorders, hepatic disorders, and glomerular diseases. Some
      animals develop clinical signs directly caused by low serum albumin
      concentration. There is strong evidence that hypoalbuminemia is associated with
      worse outcomes; however, evidence justifying albumin supplementation is lacking.
      Severe adverse events are frequently reported with administration of human serum
      albumin and there is little evidence of benefit from other products. Most
      patients will not require administration of albumin-containing products.
      Clinicians should consider early enteral nutritional supplementation in
      critically ill patients.

PMID- 27890436
TI  - Respiratory Acid-Base Disorders in the Critical Care Unit.
AB  - The incidence of respiratory acid-base abnormalities in the critical care unit
      (CCU) is unknown, although respiratory alkalosis is suspected to be common in
      this population. Abnormal carbon dioxide tension can have many physiologic
      effects, and changes in Pco2 may have a significant impact on outcome. Monitoring
      Pco2 in CCU patients is an important aspect of critical patient assessment, and
      identification of respiratory acid-base abnormalities can be valuable as a
      diagnostic tool. Treatment of respiratory acid-base disorders is largely focused
      on resolution of the primary disease, although mechanical ventilation may be
      indicated in cases with severe respiratory acidosis.

PMID- 27890437
TI  - Trends of Anti-Vascular Endothelial Growth Factor Use in Ophthalmology Among
      Privately Insured and Medicare Advantage Patients.
AB  - PURPOSE: To characterize the first 10 years of intravitreal anti-vascular
      endothelial growth factor (VEGF) medication use for ophthalmic disease, including
      bevacizumab, ranibizumab, and aflibercept. DESIGN: A retrospective cohort study
      using administrative claims data from January 1, 2006 to December 31, 2015.
      SUBJECTS: Total of 124 835 patients 18 years of age or over in the United States.
      METHODS: OptumLabs Data Warehouse, which includes administrative claims data for
      over 100 million commercially insured and Medicare Advantage individuals, was
      used to identify patients receiving intravitreal anti-VEGF injections based on
      Current Procedural Terminology codes. MAIN OUTCOME MEASURES: Total and annual
      numbers of intravitreal anti-VEGF injections, as well as injections per 1000
      enrolled patients per general category of ophthalmic disease, overall and for
      each available medication. RESULTS: There were 959 945 anti-VEGF injections among
      124 835 patients from 2006 to 2015. Among all injections, 64.6% were of
      bevacizumab, 22.0% ranibizumab, and 13.4% aflibercept; 62.7% were performed to
      treat age-related macular degeneration (AMD), 16.1% to treat diabetic retinal
      diseases (including 0.9% of all injections that were for proliferative diabetic
      retinopathy), 8.3% to treat retinal vein occlusions, and 12.9% for all other
      uses. Use of bevacizumab and ranibizumab for AMD plateaued as of 2011/2012 and
      decreased thereafter (in 2006, 58.8 and 35.3 injections/1000 AMD patients,
      respectively; in 2015, 294.4 and 100.7 injections/1000), whereas use of
      aflibercept increased (1.1 injections/1000 AMD patients in 2011 to 183.0
      injections/1000 in 2015). Bevacizumab use increased each year for diabetic
      retinal disease (2.4 injections/1000 patients with diabetic retinal disease in
      2009 to 13.6 per 1000 in 2015) while that of ranibizumab initially increased
      significantly and then declined after 2014 (0.1 in 2009 to 4.0 in 2015).
      Aflibercept use increased each year in patients with diabetic retinal diseases
      and retinal vein occlusions (both <0.1 per 1000 retinal vein occlusion patients
      in 2011, 5.6 and 140.2 in 2015). CONCLUSIONS: Intravitreal injections of anti
      VEGF medications increased annually from 2006 to 2015. Bevacizumab was the most
      common medication used, despite its lacking U.S. Food and Drug Administration
      approval to treat ophthalmic disease, and AMD was the most common condition
      treated. Ranibizumab use declined after 2014 while both the absolute and relative
      use of bevacizumab and aflibercept increased.

PMID- 27890438
TI  - Short-term clinical results of frozen shoulder treated with shoulder manipulation
      under ultrasound-guided cervical nerve root block at outpatient setting: A case
      series.
AB  - BACKGROUND: We evaluated the short-term clinical outcomes of frozen shoulder
      treatment via shoulder manipulation under ultrasound-guided cervical nerve root
      block (MUC). METHODS: This study included frozen shoulder patients who were
      unresponsive to conservative therapy for at least 6 months and were then treated
      with MUC. Patients with a rotator cuff tear, calcifying tendinitis,
      osteoarthritis, or any other shoulder disorder were excluded following X-ray,
      ultrasound, and magnetic resonance imaging evaluation. Although 25 patients were
      initially included, three patients were not followed-up for at least 1 year. We
      investigated a final total of 22 patients; the average age was 58 years and 59%
      were female. We measured shoulder pain, shoulder range of motion, and American
      Shoulder and Elbow Surgeons shoulder scores immediately prior to MUC, 1 week
      after MUC, and 1 year after MUC. A Short-Form 36-Item Health Survey was
      administered before MUC and 1 year after MUC. We used the Friedman and Wilcoxon
      signed-rank tests to identify statistical differences. Significance was defined
      as p < 0.05. RESULTS: MUC significantly improved shoulder pain during motion,
      range of motion, and American Shoulder and Elbow Surgeons scores 1 week after
      MUC. This improvement persisted at the 1-year follow-up. Seven of the eight Short
      Form 36-Item Health Survey measures were significantly improved 1 year after MUC.
      One patient (4.5%) developed Horner's syndrome, although symptoms resolved within
      several hours without treatment. CONCLUSION: MUC for frozen shoulder was safe and
      resulted in a significant improvement in shoulder pain and range of motion 1 week
      after the procedure. This improvement persisted at the 1-year follow-up.

PMID- 27890439
TI  - A Japanese nationwide multicenter survey on perioperative complications of
      corrective fusion for elderly patients with adult spinal deformity.
AB  - BACKGROUND: Recently, corrective fusion surgery for patients with adult spinal
      deformity (ASD) has become common in Japan. This study aimed to clarify the
      status of surgeries for ASD in Japan, focusing on perioperative complications. A
      nationwide multicenter survey gathering information on surgically treated ASD
      patients was conducted by the committee for Adult Spinal Deformity of the
      Japanese Scoliosis Society. METHODS: This study was a review of retrospectively
      collected data from 18 spine scoliosis centers belonging to the Japanese
      Scoliosis Society. Patients who underwent corrective fusion surgery for ASD
      between 2011 and 2013 were included. Demographics, comorbidities, surgical data,
      and complications were investigated. RESULTS: A total of 1192 patients (mean age,
      57.7 years) were included in this study. Of these, 611 patients were aged less
      than 65 years and 581 patients were aged 65 years or greater. The age
      distribution had two peaks, in the third and eighth decades. Deformities caused
      by degeneration represented 67% of the pathology in patients aged over 65 years;
      however, non-degenerative disease such as adult idiopathic scoliosis and
      syndromic or congenital deformity represented over 60% of pathology in patients
      aged less than 65 years. The iatrogenic deformity and reoperation rates were both
      less than 3%. The mean operation time and estimated blood loss were 370 min and
      1642 ml, respectively. Major perioperative complications occurred in 160 patients
      (14.5%). The incidence of complications was significantly higher in patients aged
      over 65 years, including neurological deficits, hemorrhagic shock, hematoma,
      heart failure, and surgical site infection (p < 0.05). CONCLUSIONS: Older (aged
      over 65 years) ASD patients showed greater rates of deformity due to the
      occurrence of degeneration and vertebral fractures, as well as a higher incidence
      of peri-and postoperative complications. Efforts to reduce perioperative
      complications are therefore imperative, especially for elderly ASD patients in
      our aging society.

PMID- 27890440
TI  - Three-Month Outcomes Are Poor in Stroke Patients with Cancer Despite Acute Stroke
      Treatment.
AB  - INTRODUCTION: Stroke risk is increased in cancer patients. Prognosis in these
      patients is poor, with higher in-hospital mortality and increased subsequent
      mortality. However, data on stroke in cancer patients are limited, specifically
      regarding acute stroke treatment and functional outcomes. We aim to determine the
      functional outcomes of cancer patients admitted with acute stroke. MATERIALS AND
      METHODS: We retrospectively reviewed patients carrying a diagnosis of cancer who
      were admitted with acute ischemic stroke between March 2013 and February 2016.
      Demographics, cerebrovascular risk factors, stroke characteristics including
      acute treatment, and characteristics of their cancer history and treatment were
      abstracted. The primary outcome measures included in-hospital mortality and 3
      month functional outcome (as assessed by the modified Rankin Scale [mRS] score,
      with mRS scores of 3-6 considered poor functional outcome). Further outcome
      measures included length of stay and discharge destination. FINDINGS: Forty-nine
      patients met the inclusion criteria, with a median admission National Institutes
      of Health Stroke Scale score of 8. Twelve patients (24.4%) underwent acute stroke
      treatment. The most common stroke etiology was hypercoagulability of malignancy
      (21, 42.9%). The three-month mortality was 46.9%; half of survivors had poor
      functional outcome. Functional outcomes did not differ by cancer type, stage, or
      year since diagnosis; on multivariate analysis only high admission NIHSS score
      was associated with poor functional outcome (P = .002). CONCLUSION: Nearly half
      of patients with cancer and stroke die within 3 months, and functional outcome is
      poor for 50% of 3-month survivors despite consideration of acute stroke
      treatment. Future research should address the role of hypercoagulability in the
      outcome prediction of stroke patients with cancer.

PMID- 27890441
TI  - The ability for cocaine and cocaine-associated cues to compete for attention.
AB  - In humans, reward cues, including drug cues in individuals experiencing
      addiction, are especially effective in biasing attention towards them, so much so
      they can disrupt ongoing task performance. It is not known, however, whether this
      happens in rats. To address this question, we developed a behavioral paradigm to
      assess the capacity of an auditory drug (cocaine) cue to evoke cocaine-seeking
      behavior, thus distracting thirsty rats from performing a well-learned sustained
      attention task (SAT) to obtain a water reward. First, it was determined that an
      auditory cocaine cue (tone-CS) reinstated drug-seeking equally in sign-trackers
      (STs) and goal-trackers (GTs), which otherwise vary in the propensity to
      attribute incentive salience to a localizable drug cue. Next, we tested the
      ability of an auditory cocaine cue to disrupt performance on the SAT in STs and
      GTs. Rats were trained to self-administer cocaine intravenously using an
      Intermittent Access self-administration procedure known to produce a progressive
      increase in motivation for cocaine, escalation of intake, and strong
      discriminative stimulus control over drug-seeking behavior. When presented alone,
      the auditory discriminative stimulus elicited cocaine-seeking behavior while rats
      were performing the SAT, but it was not sufficiently disruptive to impair SAT
      performance. In contrast, if cocaine was available in the presence of the cue, or
      when administered non-contingently, SAT performance was severely disrupted. We
      suggest that performance on a relatively automatic, stimulus-driven task, such as
      the basic version of the SAT used here, may be difficult to disrupt with a drug
      cue alone. A task that requires more top-down cognitive control may be needed.

PMID- 27890443
TI  - OXA-23 and ISAba1-OXA-66 class D beta-lactamases in Acinetobacter baumannii
      isolates from companion animals.
AB  - Acinetobacter baumannii is recognised as a major pathogen of nosocomial
      infections that frequently show resistance to last-resort antimicrobials. To
      investigate whether A. baumannii from companion animals harbour carbapenem
      resistance mechanisms, 223 clinical isolates obtained from veterinary clinics
      between 2000 and 2013 in Germany were screened for carbapenem-non-susceptibility
      employing meropenem-containing Mueller-Hinton agar plates. Minimum inhibitory
      concentration (MIC) data were obtained using the VITEK(r)2 system. Assignment to
      international clones (ICs) was done by multiplex PCR or repetitive sequence-based
      PCR employing the DiversiLab system. Clonality was studied using pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing (MLST). Genes encoding
      carbapenemases and aminoglycoside-modifying enzymes were detected by PCR. In
      three samples from dogs, carbapenem-resistant A. baumannii carrying the blaOXA-23
      gene on plasmids and located on transposon Tn2008 were identified. The isolates
      belonged to sequence type ST1P (clonal complex CC1/IC1/pulsotype II) and ST10P
      (CC10/IC8/pulsotype IV) according to the Pasteur MLST scheme, and to ST231Ox
      (CC109) and ST585Ox (CC447) following the Oxford scheme. Insertion sequence
      ISAba1 was identified upstream of blaOXA-66 in 58 A. baumannii isolates. MLST
      referred them to ST2P (CC2/IC2/pulsotypes I and III), ST208Ox, ST350Ox and
      ST556Ox (all CC118), respectively. PFGE suggested nosocomial spread of these
      highly related strains, which frequently demonstrated a multidrug-resistant
      phenotype, in one veterinary clinic. These data show that A. baumannii from
      companion animals reveal resistance determinants and clonal lineages of strains
      globally emerging in humans. This suggests an interspecies transmission and
      warrants molecular surveillance of A. baumannii in veterinary clinics to mitigate
      its further spread.

PMID- 27890444
TI  - T2-weighted Cardiovascular Magnetic Resonance Imaging to Delineate Ischemic
      Myocardium at Risk: Fact or Fiction?

PMID- 27890445
TI  - Acute carbon monoxide poisoning: MR imaging findings with clinical correlation.
AB  - PURPOSE: To assess the magnetic resonance imaging (MRI) findings, including
      diffusion-weighted imaging (DWI) in patients with acute carbon monoxide (CO)
      poisoning and correlate MRI findings with carboxyhemoglobin levels. MATERIALS AND
      METHODS: The MRI examinations and medical records of seven men with a mean age of
      43+/-16.0years (SD) (range: 25-63 years) with acute CO poisoning were reviewed.
      MRI examinations were analyzed with respect to lesion location, imaging
      presentation on T1- and T2-weighted images, and diffusion characteristics on DWI
      and apparent diffusion coefficient (ADC) maps. We also evaluated clinical
      features and laboratory findings including the presenting symptoms and signs,
      carboxyhemoglobin level, and treatment. RESULTS: All seven patients presented
      with mental status change. The level of carboxyhemoglobin ranged between 8.3% and
      34.8% (normal<1.5%). All seven patients (7/7, 100%) showed restricted diffusion
      of the lesions on ADC maps and bilateral involvement of globus pallidus. The mean
      ratios of ADC values was 0.63+/-0.15 (SD) (range: 0.46-0.92) on bilateral globi
      pallidi. Cerebral cortex, cerebral white matter, cerebellum, hippocampus,
      amygdala, splenium of corpus callosum, midbrain and insula were also involved.
      CONCLUSION: Bilateral globi pallidi with restricted diffusion may be a
      characteristic MRI feature in patients with acute CO poisoning. However, the
      relationship was not certain between the carboxyhemoglobin levels and the variety
      or severity of MRI findings.

PMID- 27890447
TI  - Non-iatrogenic mandibular pressure sores.

PMID- 27890442
TI  - Predominance of healthcare-associated cases among episodes of community-onset
      bacteraemia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae.
AB  - Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) are
      endemic pathogens worldwide. Infection with ESBL-PE may be associated with
      inadequate antibiotic therapy and a poor outcome. However, risk factors for ESBL
      PE community-acquired infections are ill-defined. An observational multicentre
      study was performed in 50 hospitals to identify the prevalence of and risk
      factors for community-acquired ESBL-PE bacteraemia. All patients presenting with
      community-onset Enterobacteriaceae bacteraemia were recorded over a 2-month
      period (between June and November 2013). Risk factors and 14-day outcomes of
      patients were investigated. Among 682 Enterobacteriaceae bacteraemia episodes
      recorded, 58 (8.5%) were caused by ESBL-PE. The most frequent species isolated
      were Escherichia coli (537; 76.7%) and Klebsiella spp. (68; 9.7%), of which 49
      (9.1%) and 8 (11.8%), respectively, were ESBL-producers. Most ESBL-PE episodes
      were healthcare-associated, and only 22 (38%) were apparently community-acquired.
      The main risk factor for community-acquired ESBL-PE bacteraemia was a prior
      hospital stay of >=5 days within the past year. The overall 14-day survival was
      90%; only 4 (6.9%) of 58 patients with ESBL-PE bacteraemia died. Inadequate
      initial antibiotic therapy was administered to 55% of patients with ESBL-PE
      bacteraemia but was not associated with increased 14-day mortality. Although many
      patients had community-onset ESBL-PE bacteraemia, almost two-thirds of the
      episodes were actually healthcare-associated, and true community-acquired ESBL-PE
      bacteraemia remains rare. In our essentially non-severely ill population,
      inappropriate initial therapy was not associated with a higher risk of mortality.

PMID- 27890446
TI  - Efficacy of Therapies After Galeterone in Patients With Castration-resistant
      Prostate Cancer.
AB  - BACKGROUND: Galeterone is a multi-targeted agent with activity as a CYP17
      inhibitor, androgen receptor antagonist, and also causes androgen receptor
      degradation. It has shown meaningful anti-tumor activity with a well-tolerated
      safety profile in patients with castration-resistant prostate cancer (CRPC) in
      phase I and II studies; however, the efficacy of currently approved CRPC
      therapies after treatment with galeterone is unknown. In this study, we evaluate
      prostate specific antigen (PSA) response of non-protocol therapies following
      galeterone in a subset of patients treated on the Androgen Receptor Modulation
      Optimized for Response (ARMOR) 2 study. PATIENTS AND METHODS: Patients who
      received any subsequent treatment were included. PSA response and treatment
      duration were summarized by line and type of subsequent therapy. RESULTS:
      Overall, 27 of 40 patients received >= 1 post-galeterone treatment, of whom 18
      (67%) discontinued galeterone for progression, 14 (52%) received >= 2 treatments,
      and 6 (22%) received >= 3 treatments. PSA changed by a median of -36%, -35%, and
      +60% in patients receiving first-line, second-line, and third-line therapy,
      respectively. Overall, 18 (67%) received subsequent enzalutamide, 12 (44%)
      received docetaxel, 9 (33%) received abiraterone, and 5 (19%) received
      cabazitaxel. PSA changed by a median of -27%, -34%, -39%, and 17% for patients
      receiving subsequent enzalutamide, docetaxel, abiraterone, and cabazitaxel,
      respectively, at any line. CONCLUSION: We demonstrate that CRPC therapies exhibit
      differential anti-tumor activity following galeterone. In this small cohort,
      abiraterone demonstrates the highest PSA response post-galeterone, whereas
      enzalutamide and chemotherapy have more modest activity. Larger clinical studies
      are warranted to fully evaluate the efficacy and safety of second-generation
      hormonal agents and chemotherapy post-galeterone. Predictive biomarkers will be
      critical to optimizing patient selection for sequential therapies.

PMID- 27890448
TI  - Vaccines against pseudorabies virus (PrV).
AB  - Aujeszkys disease (AD, pseudorabies) is a notifiable herpesvirus infection of
      pigs causing substantial economic losses to swine producers. AD in pigs is
      controlled by the use of vaccination with inactivated and attenuated live
      vaccines. Starting with classically attenuated live vaccines derived from low
      virulent field isolates, AD vaccination has pioneered novel strategies in animal
      disease control by the first use of genetically engineered live virus vaccines
      lacking virulence-determining genes, and the concept of DIVA, i.e. the
      serological differentiation of vaccinated from field-virus infected animals by
      the use of marker vaccines and respective companion diagnostic tests. The basis
      for this concept has been the molecular characterization of PrV and the
      identification of so-called nonessential envelope glycoproteins, e.g.
      glycoprotein E, which could be eliminated from the virus without harming viral
      replication or immunogenicity. Eradication of AD using the strategy of
      vaccination-DIVA testing has successfully been performed in several countries
      including Germany and the United States. Furthermore, by targeted genetic
      modification PrV has been developed into a powerful vector system for expression
      of foreign genes to vaccinate against several infectious diseases of swine, while
      heterologous vector systems have been used for expression of major immunogens of
      PrV. This small concise review summarizes the state-of-the-art information on PrV
      vaccines and provides an outlook for the future.

PMID- 27890449
TI  - Independent evolution of genomic characters during major metazoan transitions.
AB  - Metazoan evolution encompasses a vast evolutionary time scale spanning over 600
      million years. Our ability to infer ancestral metazoan characters, both
      morphological and functional, is limited by our understanding of the nature and
      evolutionary dynamics of the underlying regulatory networks. Increasing coverage
      of metazoan genomes enables us to identify the evolutionary changes of the
      relevant genomic characters such as the loss or gain of coding sequences, gene
      duplications, micro- and macro-synteny, and non-coding element evolution in
      different lineages. In this review we describe recent advances in our
      understanding of ancestral metazoan coding and non-coding features, as deduced
      from genomic comparisons. Some genomic changes such as innovations in gene and
      linkage content occur at different rates across metazoan clades, suggesting some
      level of independence among genomic characters. While their contribution to
      biological innovation remains largely unclear, we review recent literature about
      certain genomic changes that do correlate with changes to specific developmental
      pathways and metazoan innovations. In particular, we discuss the origins of the
      recently described pharyngeal cluster which is conserved across deuterostome
      genomes, and highlight different genomic features that have contributed to the
      evolution of this group. We also assess our current capacity to infer ancestral
      metazoan states from gene models and comparative genomics tools and elaborate on
      the future directions of metazoan comparative genomics relevant to evo-devo
      studies.

PMID- 27890450
TI  - SRC2-3 binds to vitamin D receptor with high sensitivity and strong affinity.
AB  - Vitamin D receptor (VDR) is a member of the nuclear receptor superfamily and
      regulates the expression of target genes through ligand binding. To express the
      target gene, coactivator binding to the VDR/ligand complex is essential. Although
      there are many coactivators in living cells, precise interactions between
      coactivators and VDR have not been clarified. Here, we synthesized two
      coactivator peptides, DRIP205-2 and SRC2-3, evaluated their affinity for the
      ligand-binding domain (LBD) of VDR using 1alpha,25-dihydroxyvitamin D3, partial
      agonist 1, and antagonist 2 by surface plasmon resonance (SPR), and assessed
      their interaction modes with VDR-LBD using X-ray crystallographic analysis. This
      study showed that the SRC2-3 peptide is more sensitive to the ligands (agonist,
      partial agonist, and antagonist) and shows more intimate interactions with VDR
      LBD than DRIP205-2 peptide.

PMID- 27890451
TI  - Sniffing the diagnosis: Olfactory testing in neurodegenerative parkinsonism.
AB  - OBJECTIVE: To determine the diagnostic utility of olfactory testing in patients
      with neurodegenerative parkinsonism. METHODS: The Sniffin' Sticks test battery
      for assessment of odor identification, discrimination, and threshold was applied
      to patients with Parkinson's disease (PD), multiple system atrophy (MSA) and
      progressive supranuclear palsy (PSP) as well as healthy controls (HC). Two
      different cohorts were analyzed: A PD/healthy control that included PD patients
      and HC as well as a PD/diseased control cohort for which patients PD, MSA and PSP
      were recruited. The former cohort was exploited to calculate cut-off values that
      discriminate PD patients from HC with a sensitivity (sensitivity-weighted cut
      off) or specificity (specificity-weighted cut-off) exceeding 95%, respectively.
      The PD/diseased controls cohort was used to determine the diagnostic accuracy
      using these cut-off values in discriminating patients with neurodegenerative
      parkinsonism. RESULTS: PD patients (n = 67) performed significantly worse in
      olfactory testing than HC (n = 41) and patients with MSA (n = 23) or PSP (n =
      23). There was no significant difference in olfactory function between MSA and
      PSP patients. Diagnostic performance of the identification subscore was similar
      to the sum score of the Sniffin' Sticks test (AUC identification test 0.94, AUC
      sum score 0.96), while threshold and discrimination subscores were inferior. In
      patients with parkinsonism, the specificity-weighted cut-off predicted a
      diagnosis of PD with a sensitivity and specificity of 76.6 and 87.0%,
      respectively. The discriminative value of this cut-off in separating PD from MSA
      was 76.7% (sensitivity) and 95.7% (specificity). The corresponding, prevalence
      adjusted positive predictive value of olfactory testing exceeded 95%.
      CONCLUSIONS: Our data suggest that assessment of olfactory function, particularly
      odor identification, can be useful to discriminate PD from atypical parkinsonian
      disorders, particularly MSA patients.

PMID- 27890452
TI  - Interhypothalamic adhesion and multiple cerebral abnormalities in a 2-year-old
      boy.

PMID- 27890453
TI  - Transition of care: A set of pharmaceutical interventions improves hospital
      discharge prescriptions from an internal medicine ward.
AB  - BACKGROUND: Continuity of care between hospitals and community pharmacies needs
      to be improved to ensure medication safety. This study aimed to evaluate whether
      a set of pharmaceutical interventions to prepare hospital discharge facilitates
      the transition of care. METHODS: This study took place in the internal medicine
      ward and in surrounding community pharmacies. The intervention group's patients
      underwent a set of pharmaceutical interventions during their hospital stay:
      medication reconciliation at admission, medication review, and discharge
      planning. The two groups were compared with regards to: number of community
      pharmacist interventions, time spent on discharge prescriptions, and number of
      treatment changes. RESULTS: Comparison between the groups showed a much lower
      (77% lower) number of community pharmacist interventions per discharge
      prescription in the intervention (n=54 patients) compared to the control group
      (n=64 patients): 6.9 versus 1.6 interventions, respectively (p<0.0001); less time
      working on discharge prescriptions; less interventions requiring a telephone call
      to a hospital physician. The number of medication changes at different steps was
      also significantly lower in the intervention group: 40% fewer (p<0.0001) changes
      between hospital admission and discharge, 66% fewer (p<0.0001) between hospital
      discharge and community pharmacy care, and 25% fewer (p=0.002) between community
      pharmacy care and care by a general practitioner. CONCLUSION: An intervention
      group underwent significantly fewer medication changes in subsequent steps in the
      transition of care after a set of interventions performed during their hospital
      stay. Community pharmacists had to perform fewer interventions on discharge
      prescriptions. Altogether, this improves continuity of care.

PMID- 27890454
TI  - Effect of phototherapy on B and T lymphocytes in Egyptian infants suffering from
      neonatal jaundice.
AB  - BACKGROUND: Neonatal jaundice is one of the most common problems that affect
      newborn infants, and phototherapy is usually used for treatment. OBJECTIVES:
      Evaluation of the effect of phototherapy on neonatal immune system through
      measuring the percentage of B and T lymphocytes and determining the frequency of
      development of infections and need for hospitalisation during the first six
      months of life. METHODS: A prospective cohort study was conducted on 50 full term
      new-borns; 25 with indirect hyperbilirubinaemia and treated with conventional
      phototherapy and 25 healthy matched neonates as untreated controls. The
      percentages of CD19+, CD4+ and CD8+ lymphocytes were measured by flow cytometry
      before phototherapy and 72h after exposure. Follow-up of the study group for the
      occurrence of infections for a period of six months after phototherapy. RESULTS:
      The study showed a significant difference in CD19+ lymphocytes percentage between
      patients before phototherapy and controls (P value<0.01), also a significant
      correlation between serum levels of total bilirubin in patients and CD19+
      lymphocytes percentage (P value<0.05). There was no significant difference
      between the percentages of CD19+, CD4+ and CD8+ lymphocytes in patients before or
      after 72h of exposure to phototherapy (P value>0.05). Also, there was no
      correlation between the percentages of CD19+, CD4+ and CD8+ lymphocytes after 72h
      of exposure to phototherapy and the occurrence of infections (Gastrointestinal
      tract and Respiratory tract infection) after six months of follow-up (P
      value>0.05). More studies are needed with larger number of patients to determine
      the effect of phototherapy on immune system.

PMID- 27890455
TI  - The detection of microbial DNA but not cultured bacteria is associated with
      increased mortality in patients with suspected sepsis-a prospective multi-centre
      European observational study.
AB  - OBJECTIVES: Blood culture results inadequately stratify the mortality risk in
      critically ill patients with sepsis. We sought to establish the prognostic
      significance of the presence of microbial DNA in the bloodstream of patients
      hospitalized with suspected sepsis. METHODS: We analysed the data collected
      during the Rapid Diagnosis of Infections in the Critically Ill (RADICAL) study,
      which compared a novel culture-independent PCR/electrospray ionization-mass
      spectrometry (ESI-MS) assay with standard microbiological testing. Patients were
      eligible for the study if they had suspected sepsis and were either hospitalized
      or were referred to one of nine intensive care units from six European countries.
      The blood specimen for PCR/ESI-MS assay was taken along with initial blood
      culture taken for clinical indications. RESULTS: Of the 616 patients recruited to
      the RADICAL study, 439 patients had data on outcome, results of the blood culture
      and PCR/ESI-MS assay available for analysis. Positive blood culture and PCR/ESI
      MSI result was found in 13% (56/439) and 40% (177/439) of patients, respectively.
      Either a positive blood culture (p 0.01) or a positive PCR/ESI-MS (p 0.005) was
      associated with higher SOFA scores on enrolment to the study. There was no
      difference in 28-day mortality observed in patients who had either positive or
      negative blood cultures (35% versus 32%, p 0.74). However, in patients with a
      positive PCR/ESI-MS assay, mortality was significantly higher in comparison to
      those with a negative result (42% versus 26%, p 0.001). CONCLUSIONS: Presence of
      microbial DNA in patients with suspected sepsis might define a patient group at
      higher risk of death.

PMID- 27890456
TI  - Introduction to the supplement on 'Vaccines for mutual protection'.

PMID- 27890457
TI  - The role of whole genome sequencing in antimicrobial susceptibility testing of
      bacteria: report from the EUCAST Subcommittee.
AB  - Whole genome sequencing (WGS) offers the potential to predict antimicrobial
      susceptibility from a single assay. The European Committee on Antimicrobial
      Susceptibility Testing established a subcommittee to review the current
      development status of WGS for bacterial antimicrobial susceptibility testing
      (AST). The published evidence for using WGS as a tool to infer antimicrobial
      susceptibility accurately is currently either poor or non-existent and the
      evidence / knowledge base requires significant expansion. The primary comparators
      for assessing genotypic-phenotypic concordance from WGS data should be changed to
      epidemiological cut-off values in order to improve differentiation of wild-type
      from non-wild-type isolates (harbouring an acquired resistance). Clinical
      breakpoints should be a secondary comparator. This assessment will reveal whether
      genetic predictions could also be used to guide clinical decision making.
      Internationally agreed principles and quality control (QC) metrics will
      facilitate early harmonization of analytical approaches and interpretive criteria
      for WGS-based predictive AST. Only data sets that pass agreed QC metrics should
      be used in AST predictions. Minimum performance standards should exist and
      comparative accuracies across different WGS laboratories and processes should be
      measured. To facilitate comparisons, a single public database of all known
      resistance loci should be established, regularly updated and strictly curated
      using minimum standards for the inclusion of resistance loci. For most bacterial
      species the major limitations to widespread adoption for WGS-based AST in
      clinical laboratories remain the current high-cost and limited speed of inferring
      antimicrobial susceptibility from WGS data as well as the dependency on previous
      culture because analysis directly on specimens remains challenging. For most
      bacterial species there is currently insufficient evidence to support the use of
      WGS-inferred AST to guide clinical decision making. WGS-AST should be a funding
      priority if it is to become a rival to phenotypic AST. This report will be
      updated as the available evidence increases.

PMID- 27890458
TI  - Amoxicillin dosing recommendations are very different in European countries: a
      cross-sectional survey.

PMID- 27890459
TI  - Relationship of systemic cytokine concentrations to cognitive function over two
      years in women with early stage breast cancer.
AB  - : Cancer and its treatment are frequently associated with cancer-related
      cognitive impairment (CRCI). While CRCI has been associated with linked to
      chemotherapy, there is increasing evidence that the condition may start prior to
      treatment and for some, remain unresolved after active treatment and into
      survivorship. Although the pathophysiology of the condition is complex,
      alterations in systemic cytokines, signaling molecules activated in response to
      infection or injury that trigger inflammation, are a possible mechanism linked to
      cognitive dysfunction in breast cancer and other conditions. Given the
      conflicting results in the literature, the lack of focus on domain specific
      cognitive testing, and the need for a longer time period given the multiple
      modalities of standard treatments for early-stage breast cancer, this
      longitudinal study was conducted to address these gaps. METHODS: We assessed 75
      women with early-stage breast cancer at five points over two years, starting
      prior to the initial chemotherapy through 24months after chemotherapy initiation.
      Measures included a validated computerized evaluation of domain-specific
      cognitive functioning and a 17-plex panel of plasma cytokines. Linear mixed
      effects models were applied to test the relationships of clinical variables and
      cytokine concentrations to each cognitive domain. RESULTS: Levels and patterns of
      cytokine concentrations varied over time: six of the 17 cytokines (IL-6, IL-12,
      IL-17, G-CSF, MIPS-1beta, and MCP-1) had the most variability. Some cytokine
      levels (e.g., IL-6) increased during chemotherapy but then decreased
      subsequently, while others (e.g., IL-17) consistently declined from baseline over
      time. There were multiple relationships among cytokines and cognition, which
      varied over time. At baseline, elevated concentrations of G-CSF and reduced
      concentrations of IL-17 were associated with faster psychomotor speed. At the
      second time-point (prior to the mid-chemotherapy), multiple cytokines had
      significant associations with psychomotor speed, complex attention, executive
      function, verbal memory, cognitive flexibility, composite memory and visual
      memory. Six months after chemotherapy initiation and at the one-year point, there
      were multiple, significant relationships among cytokines and multiple cognitive.
      At two years, fewer significant relationships were noted; however, lower
      concentrations of IL-7, a hematopoietic cytokine, were associated with better
      psychomotor speed, complex attention, and memory (composite, verbal and visual).
      MCP-1 was inversely associated with psychomotor speed and complex attention and
      higher levels of MIP-1beta were related to better complex attention. CONCLUSION:
      Levels and patterns of cytokines changed over time and demonstrated associations
      with domain-specific cognitive functioning that varied over time. The observed
      associations between cytokines and cognitive performance provides evidence that
      not only prototypical cytokines (i.e., IL-6, TNF-alpha, and IL1-beta) but also
      cytokines from multiple classes may contribute to the inflammatory environment
      that is associated with cognitive dysfunction. Future studies to better delineate
      the cytokine changes, both individually and in networks, are needed to precisely
      assess a mechanistic link between cytokines and cognitive function in women
      receiving treatments for breast cancer.

PMID- 27890460
TI  - Prevalence of Small Intestinal Bacterial Overgrowth in Multiple Sclerosis: a Case
      Control Study from China.
AB  - OBJECTIVE: It's hypothesized that gastrointestinal microbiota might play an
      important role in pathogenesis of multiple sclerosis (MS). The aim of the present
      study was to assess the prevalence of small intestinal bacterial overgrowth
      (SIBO) in MS patients compared with sex and age matched controls without MS.
      METHODS: The present study was a case-control type, it included 118 patients with
      definitive MS and 118 age-sex matched controls. Progression of disability was
      assessed using the Multiple Sclerosis Severity Score (MSSS). All patients and
      controls underwent the glucose breath test to assess SIBO. RESULTS: Forty-five of
      the 118 MS patients were SIBO positive (38.14%; 95%CI: 29.37%-46.90%) compared
      with 10 of 118 in the control group (8.47%; 95% confidence interval [CI]: 3.45%
      13.50%); the difference was statistically significant (P<0.0001; Odds ratios
      (OR), 4.50; 95% CI, 2.38-8.50). In addition, 102 out of the 118 patients (86.4%)
      presented at least one GI symptom. Constipation (78.0%), Bloating (46.6%), and
      fecal incontinence (44.1%) were common. Multivariate analysis showed that
      expanded disability status scale (EDSS) score and MSSS were the only factors
      associated with the SIBO-positive status in MS patients (OR, 3.44; 95% CI, 1.56
      6.99; and OR, 2.76; 95% CI, 1.42-4.94, respectively). CONCLUSION: SIBO is highly
      prevalent in Chinese patients with MS. Further analytical work is required to
      establish a causal association between SIBO and MS risk and progression.

PMID- 27890461
TI  - Muscle weakness in respiratory and peripheral skeletal muscles in a mouse model
      for nebulin-based nemaline myopathy.
AB  - Nemaline myopathy is among the most common non-dystrophic congenital myopathies,
      and is characterized by the presence of nemaline rods in skeletal muscles fibers,
      general muscle weakness, and hypotonia. Although respiratory failure is the main
      cause of death in nemaline myopathy, only little is known regarding the
      contractile strength of the diaphragm, the main muscle of inspiration. To
      investigate diaphragm contractility, in the present study we took advantage of a
      mouse model for nebulin-based nemaline myopathy that we recently developed. In
      this mouse model, exon 55 of Neb is deleted (NebDeltaExon55), a mutation
      frequently found in patients. Diaphragm contractility was determined in
      permeabilized muscle fibers and was compared to the contractility of
      permeabilized fibers from three peripheral skeletal muscles: soleus, extensor
      digitorum longus, and gastrocnemius. The force generating capacity of diaphragm
      muscle fibers of NebDeltaExon55 mice was reduced to 25% of wildtype levels,
      indicating severe contractile weakness. The contractile weakness of diaphragm
      fibers was more pronounced than that observed in soleus muscle, but not more
      pronounced than that observed in extensor digitorum longus and gastrocnemius
      muscles. The reduced muscle contractility was at least partly caused by changes
      in cross-bridge cycling kinetics which reduced the number of bound cross-bridges.
      The severe diaphragm weakness likely contributes to the development of
      respiratory failure in NebDeltaExon55 mice and might explain their early,
      postnatal death.

PMID- 27890462
TI  - Radiation pneumonitis following hepatic yttrium-90 radioembolization.

PMID- 27890463
TI  - Is pleurodesis with 50% glucose solution in patients with spontaneous
      pneumothorax safe?: A case series.

PMID- 27890464
TI  - Pleuropericardial Cyst: Uncommon Location and Presentation.

PMID- 27890465
TI  - Palbociclib improves survival in advanced breast cancer.

PMID- 27890466
TI  - Cabozantinib improves clinical outcomes in renal cancer.

PMID- 27890467
TI  - Use of hyperbaric oxygen therapy and PEGylated carboxyhemoglobin bovine in a
      Jehovah's Witness with life-threatening anemia following postpartum hemorrhage.
AB  - We present a case of a Jehovah's Witness patient who refused blood products, with
      the exception of albumin and clotting factors, and underwent cesarean section
      under spinal anesthesia complicated by postpartum hemorrhage. She was fluid
      resuscitated and treated with multiple uterotonics and internal iliac artery
      embolization. Because of agitation she required emergency tracheal intubation.
      Her hemoglobin concentration dropped from a preoperative value of 12mg/dL to
      3mg/dL on postoperative day one. She was acidotic, requiring vasopressors for
      hemodynamic stability and remained ventilated and sedated. She was treated with
      daily erythropoietin, iron therapy and cyanocobalamin. Because of ongoing
      hemorrhage, continued acidemia and vasopressor requirements she was co-treated
      with PEGylated carboxyhemoglobin bovine and hyperbaric oxygen therapy to reverse
      her oxygen debt. On postoperative day eight her hemoglobin concentration was
      7mg/dL, she was hemodynamically stable and vasopressors were discontinued. She
      was extubated and discharged from the intensive care unit on postoperative day
      eight. This report highlights the multiple modalities used in treating a severely
      anemic patient who refused blood, the use of an investigational new drug, the
      process of obtaining this drug via the United States Food and Drug Administration
      emergency expanded access regulation for single patient clinical treatment, and
      ethical dilemmas faced during treatment.

PMID- 27890468
TI  - Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar
      Disorder: Evidence From Genome-wide Association Study Meta-analysis.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder
      (BPD) are frequently co-occurring and highly heritable mental health conditions.
      We hypothesized that BPD cases with an early age of onset (<=21 years old) would
      be particularly likely to show genetic covariation with ADHD. METHODS: Genome
      wide association study data were available for 4609 individuals with ADHD, 9650
      individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically
      developing controls. We conducted a cross-disorder genome-wide association study
      meta-analysis to identify whether the observed comorbidity between ADHD and BPD
      could be due to shared genetic risks. RESULTS: We found a significant single
      nucleotide polymorphism-based genetic correlation between ADHD and BPD in the
      full and age-restricted samples (rGfull = .64, p = 3.13 * 10-14; rGrestricted =
      .71, p = 4.09 * 10-16). The meta-analysis between the full BPD sample identified
      two genome-wide significant (prs7089973 = 2.47 * 10-8; prs11756438 = 4.36 * 10-8)
      regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the
      analyses to BPD cases with an early onset yielded one genome-wide significant
      association (prs58502974 = 2.11 * 10-8) on chromosome 5 in the ADCY2 gene.
      Additional nominally significant regions identified contained known expression
      quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2,
      and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an
      allele-specific expressed gene in neuronal tissue. CONCLUSIONS: The single
      nucleotide polymorphism-based genetic correlation between ADHD and BPD is
      substantial, significant, and consistent with the existence of genetic overlap
      between ADHD and BPD, with potential differential genetic mechanisms involved in
      early and later BPD onset.

PMID- 27890469
TI  - Methamphetamine Addiction Vulnerability: The Glutamate, the Bad, and the Ugly.
AB  - BACKGROUND: The high prevalence and severity of methamphetamine (MA) abuse
      demands greater neurobiological understanding of its etiology. METHODS: We
      conducted immunoblotting and in vivo microdialysis procedures in MA high/low
      drinking mice, as well as in isogenic C57BL/6J mice that varied in their MA
      preference/taking, to examine the glutamate underpinnings of MA abuse
      vulnerability. Neuropharmacological and Homer2 knockdown approaches were also
      used in C57BL/6J mice to confirm the role for nucleus accumbens (NAC)
      glutamate/Homer2 expression in MA preference/aversion. RESULTS: We identified a
      hyperglutamatergic state within the NAC as a biochemical trait corresponding with
      both genetic and idiopathic vulnerability for high MA preference and taking. We
      also confirmed that subchronic subtoxic MA experience elicits a
      hyperglutamatergic state within the NAC during protracted withdrawal,
      characterized by elevated metabotropic glutamate 1/5 receptor function and Homer2
      receptor-scaffolding protein expression. A high MA-preferring phenotype was
      recapitulated by elevating endogenous glutamate within the NAC shell of mice and
      we reversed MA preference/taking by lowering endogenous glutamate and/or Homer2
      expression within this subregion. CONCLUSIONS: Our data point to an idiopathic,
      genetic, or drug-induced hyperglutamatergic state within the NAC as a mediator of
      MA addiction vulnerability.

PMID- 27890470
TI  - sGC stimulators: Evidence for riociguat beyond groups 1 and 4 pulmonary
      hypertension.
AB  - Pulmonary hypertension (PH) is a chronic cardiopulmonary disorder that if left
      untreated, progresses rapidly and is ultimately fatal. The World Health
      Organization (WHO) has classified PH into 5 distinct groups according to
      pathophysiology, hemodynamic characteristics, and clinical presentation.
      Dysfunction in the nitric oxide (NO) pathway plays a key role in the pulmonary
      hypertension disease process, including in WHO Groups 2 and 3 PH. PH is
      associated with endothelial dysfunction, impaired synthesis of NO, and
      insufficient stimulation of the NO-soluble guanylate cyclase (sGC)-cyclic
      guanosine monophosphate (cGMP) pathway, which reduces cGMP production. cGMP
      regulates vascular tone, cellular proliferation, inflammation, and fibrosis and
      its depletion can lead to a variety of abnormalities, including pulmonary
      vasoconstriction, impaired vascular remodeling, and in situ thrombosis. This
      review will examine a novel class of drugs called sGC stimulators which directly
      stimulate sGC independently of NO, leading to increased production of cGMP.

PMID- 27890471
TI  - Rationale and study design of MOTION: A phase 4, prospective, single-arm, open
      label study to measure outcomes in patients with pulmonary arterial hypertension
      not on active treatment.
AB  - In clinical trials of treatments for pulmonary arterial hypertension (PAH),
      objective measures, such as 6-min walk distance (6MWD) are limited in their
      ability to characterize the impact of PAH therapy from a patient's perspective.
      Few clinical studies have evaluated the primary effects of pharmacologic
      treatment on patient-reported outcomes, such as symptoms, health-related quality
      of life (HRQoL), and productivity. MOTION (NCT02191137) is a prospective,
      multicenter, single-arm, open-label, phase 4 trial designed to assess whether
      riociguat monotherapy will improve patient-reported outcomes in patients with PAH
      in the United States who are not currently on treatment. Following a screening
      period of up to 14 days, eligible subjects will receive riociguat (0.5-2.5 mg
      TID) during a 10-week titration phase and a 14-week maintenance phase. The
      primary endpoint is change from baseline in the Living with Pulmonary
      Hypertension (LPH) questionnaire, a disease-specific HRQoL measure, after 24
      weeks of riociguat treatment. The Short Form-12 Health Survey (SF-12) and the
      Work Limitations Questionnaire 8 (WLQ-8) will also be utilized to assess patient
      reported outcomes. Other variables include change from baseline in World Health
      Organization functional class, 6MWD, and modified Borg Dyspnea Index. In
      addition, accelerator band activity will be validated against the 6MWD test.
      Safety will also be assessed. The MOTION trial will provide information on the
      effect of riociguat on patient-reported outcomes in PAH patients in the United
      States who are not currently on active treatment through the use of disease
      specific and generic HRQoL measures (LPH and SF-12) and a measure of worker
      productivity (WLQ-8).

PMID- 27890472
TI  - DNA damage talks to inflammation.
AB  - Interleukin-1 alpha (IL-1alpha) and beta (IL-1beta) are pleiotropic cytokines
      affecting multiple cells and regulating many immune and inflammatory responses.
      The recent finding that nuclear IL-1alpha is recruited to sites of DNA damage,
      and its ability to actively sense and report genotoxic stress to the surrounding
      tissue, dramatically alters the way we view IL-1 biology. This discovery add a
      new face to the classical "danger theory" and show that danger signaling is not
      strictly limited to passive release or dying cells. Most importantly, as now
      physiological stresses are linked to the release or secretion of IL-1alpha,
      chronic danger signaling and the alarmin inhibition should be considered as a new
      therapeutic approach for many diseases that are characterized by ongoing DNA
      damage, stress signaling and inflammation.

PMID- 27890473
TI  - The persistence of and resistance to social norms regarding the appropriate
      amount to Eat: A preliminary investigation.
AB  - We conducted a preliminary investigation on the resistance to, and persistence
      of, social influence regarding the appropriate amount to eat, defined in terms of
      eating an amount similar to that eaten by a confederate. Participants ate pizza
      both alone and in the presence of remote confederates presenting either a high or
      low eating norm. In the portion of the experiment examining resistance to social
      influence, participants given an initial opportunity to form a personal eating
      norm by eating alone for one session in the absence of social influence were no
      more resistant to low eating norms than were those who had no such opportunity;
      however, those who ate alone for two or three prior sessions did show resistance.
      For the high eating norm, it took three eating alone sessions to create
      resistance. In the portion of the experiment examining persistence of social
      influence, when participants ate alone following a session with norm-setting
      remote confederates, the effect of the social influence persisted. However, the
      persistence effect varied by norm and weakened over time. Participants modeled a
      low eating norm for only one additional session and the size of the effect was
      markedly weaker. By contrast, the high norm persisted for all of the remaining
      sessions. Thus, individuals' social influence histories can affect their eating.

PMID- 27890474
TI  - An exploratory study of Mindfulness Based Stress Reduction for emotional eating.
AB  - Emotional eating is an important predictor of weight loss and weight regain after
      weight loss. This two part study's primary aim was to explore changes in
      emotional eating in a general population of individuals taking the Mindfulness
      Based Stress Reduction (MBSR) program, with a secondary aim to explore whether
      changes in mindfulness predicted changes in emotional eating. Self-reported
      survey data exploring these questions were collected before and after the
      intervention for two sequential studies (Study 1 and Study 2). While there were
      no control groups for either study, in both studies emotional eating scores
      following the MBSR were significantly lower than scores prior to taking the MBSR
      (p < 0.001; p < 0.001) In Study 2, changes in mindfulness were correlated with
      changes in emotional eating (r = 0.317, p = 0.004). These results suggest that
      MBSR may be an effective intervention for emotional eating, and that further
      research is warranted to examine effects on weight loss and maintenance.

PMID- 27890476
TI  - Spatial and temporal dynamics of macrophyte cover in a large regulated river.
AB  - The River Ebro basin is extensively dammed. Dams alter the geomorphological
      functioning of the river by altering its flow regime (e.g. reducing mean and
      maximum discharges), increasing bed stability (armouring) and decreasing
      turbidity (water clarity). These effects, together with an increase in nutrient
      concentrations and water temperature, have generated optimal conditions for the
      proliferation of aquatic macrophytes. In this paper, we analyse the temporal and
      spatial changes of macrophyte cover in the lowermost Ebro through a series of
      field campaigns carried out between 2009 and 2010. Special attention was paid to
      the spatial distribution of macrophytes in relation to flow hydraulics, channel
      geometry and bed sedimentology. Temporal changes in macrophyte cover were
      analysed in relation to the frequency and magnitude of both natural floods and
      flushing flows (artificial flow releases from dams with generally a magnitude
      that equates around a2-year flood in the river). Spatially, the proportion of
      macrophytes along the reaches showed a variable pattern, with a succession of
      areas with both high and low plant density, coinciding with the alternation of
      riffles and pools in the channel. The highest values of plant cover (>65%)
      occurred in riffles and in transition to riffle areas, while the lowest densities
      (1% or almost negligible) were observed in pools and transition to pool areas.
      Water depth and the grain-size distribution of the riverbed materials (i.e. D84),
      are found to be the main factors controlling the degree of plant cover in the
      lower Ebro. Temporally, the macrophyte proportion varied during the hydrological
      year, with a clear increment from late spring to early autumn (i.e. vegetation
      cover reached 40%, on average, of the channel surface). Macrophyte coverage
      decreases immediately following a flushing flow but in the long term, vegetation
      re-occupied the area again, even slightly increasing in some sections; overall,
      the mean percentage of macrophyte cover was 19% higher at the end of the study
      period, despite the numerous flow events occurred on the meantime. This increase
      enhanced riverbed stability, which in turn reduced the possibility for bed
      material entrainment. This study empirically confirms the necessity of improving
      the management options applied in the lower Ebro with complementary measures to
      help maximise the efficiency of flow releases (for instance, subject the
      macrophytes to a severe hydrological stress by decreasing discharge before a
      given flushing flow, undertake localise mechanical removal of plants in areas
      where density is high, and increase the frequency of floods in winter time when
      macrophyte stands are weaker).

PMID- 27890475
TI  - Slowed dark adaptation in older eyes; effect of location.
AB  - PURPOSE: The rate of rod sensitivity recovery following a photobleach is a basic
      measure of the integrity of the outer retina. Rods are selectively impaired in
      aging and many disorders of the retina, notably Age-Related Macular Degeneration
      (AMD). It is not known for certain whether the age-related deficit is a pan
      retinal effect or if there are localised regions of impaired rod function. To
      address this important issue a dual arc stimulus was developed that samples
      sensitivity recovery in two retinal locations. METHODS: Arc-shaped stimuli were
      presented on a black CRT screen at two locations, in the inferior visual field.
      Following a bleach, which was localised to the stimuli, recovery of sensitivity
      was measured using a modified method of adjustment technique. Neutral density
      filters were used to extend the luminance range of the CRT. Sensitivity recovery
      functions were fitted by non-linear regression to a seven-parameter model.
      RESULTS: Pairs of sensitivity recovery functions were generated from the stimuli.
      The cone phases of these functions were identical. The slopes of the S2 sections
      of the curves were steeper for the outer stimuli for both young (p < 0.001) and
      older (p = 0.003) observers. The difference between the two was the same for the
      two groups. The alpha point was reached slightly earlier for the young observers
      and with the outer stimulus but neither of these effects reached statistical
      significance. The beta point occurred earlier for the outer stimuli and this
      effect was statistically significant only for the older group. CONCLUSIONS: The
      method places minimal demands on observers. The fact that rod sensitivity
      recovery is slowed in the older normal eye to the same extent in the two
      locations suggests that this deficit may be uniform across the retina. As there
      are localised losses in scotopic function in AMD, the technique is ideally suited
      to distinguishing impaired recovery dynamics due to normal ageing from those
      caused by disease.

PMID- 27890477
TI  - Implementing participatory monitoring in river management: The role of
      stakeholders' perspectives and incentives.
AB  - Involving local stakeholders in monitoring has the potential to stimulate
      learning and improve management responses. However, there is limited
      understanding about factors which influence implementation and success. This
      paper reviews local stakeholders' perceptions with respect to the construction of
      longitudinal dams in the Dutch river Waal, and explores their incentives to be
      involved in monitoring the effects of this intervention. Interviews with key
      stakeholders showed that concerns and (dis)trust are important incentives for
      participating in monitoring. Surveys of local residents, recreational anglers and
      boaters, and shipping professionals mapped their level of trust, attachment to
      the river landscape and evaluation of the effects of the longitudinal dams. Our
      case study shows that incentives for participation differ between stakeholder
      groups, and that research into their perceptions of the local environment can
      inform water managers on how to involve these groups in participatory monitoring.

PMID- 27890478
TI  - Association of Dietary Habits with Psychosocial Outcomes in Women with
      Fibromyalgia: The al-Andalus Project.
AB  - BACKGROUND: Fibromyalgia (FM) is a complex multidimensional disorder with pain as
      its main symptom. Fibromyalgia imposes a psychosocial burden on individuals that
      negatively impacts quality of life. The relationship of dietary habits with these
      psychosocial aspects is still unclear. OBJECTIVE: The purpose of this cross
      sectional study was to assess dietary habits in a representative sample of women
      with FM and to explore their association with mental health, depression, and
      optimism in this population. DESIGN: A cross-sectional study was conducted
      between November 2011 and January 2013. PARTICIPANTS: The study sample comprised
      486 women (ages 35 to 65 years) with FM from Andalucia (southern Spain). MAIN
      OUTCOME MEASURES: Mental health, depression, and optimism were evaluated by means
      of the mental component scale of the 36-item Short-Form Health Survey, the Beck
      Depression Inventory (BDI-II), and the Life Orientation Test Revised,
      respectively. A short form of a validated food frequency questionnaire was used
      to assess dietary habits. STATISTICAL ANALYSES PERFORMED: Analysis of covariance
      was used to assess associations between dietary habits and mental health,
      depression, and optimism. The presence of severe depression (BDI-II >=29) as a
      function of dietary habits was examined with logistic regression. RESULTS: A
      daily or almost-daily consumption of fruit and vegetables and a moderate
      consumption of fish (2 to 5 servings per week) were associated with higher scores
      in mental health (P<0.001, P<0.05, and P<0.001, respectively) and lower levels of
      depression (P<0.001, P<0.01, and P<0.01, respectively). A daily or almost-daily
      consumption of vegetables and a moderate consumption of dairy products and fish
      were associated with higher levels of optimism (P<0.05, P<0.05, and P<0.001,
      respectively). A daily or almost-daily consumption of cured meats and sweetened
      beverages were associated with higher levels of depression and lower levels of
      optimism, respectively (both P<0.05). CONCLUSION: The results this study suggest
      that a daily or almost-daily intake of fruit and vegetables and a moderate intake
      of fish may be associated with more favorable psychosocial outcomes in women with
      FM. Conversely, excessive intake of cured meats and sweetened beverages was
      related to worse scores in optimism and depression outcomes. Future research
      analyzing dietary patterns as well as intervention studies evaluating the effects
      of healthy dietary patterns on psychosocial and physical outcomes in individuals
      with FM are warranted.

PMID- 27890479
TI  - Heart rate variability and psychometric responses to overload and tapering in
      collegiate sprint-swimmers.
AB  - OBJECTIVES: The purpose of this study was to evaluate cardiac-parasympathetic and
      psychometric responses to competition preparation in collegiate sprint-swimmers.
      Additionally, we aimed to determine the relationship between average vagal
      activity and its daily fluctuation during each training phase. DESIGN:
      Observational. METHODS: Ten Division-1 collegiate sprint-swimmers performed heart
      rate variability recordings (i.e., log transformed root mean square of successive
      RR intervals, lnRMSSD) and completed a brief wellness questionnaire with a
      smartphone application daily after waking. Mean values for psychometrics and
      lnRMSSD (lnRMSSDmean) as well as the coefficient of variation (lnRMSSDcv) were
      calculated from 1 week of baseline (BL) followed by 2 weeks of overload (OL) and
      2 weeks of tapering (TP) leading up to a championship competition. RESULTS:
      Competition preparation resulted in improved race times (p<0.01). Moderate
      decreases in lnRMSSDmean, and Large to Very Large increases in lnRMSSDcv,
      perceived fatigue and soreness were observed during the OL and returned to BL
      levels or peaked during TP (p<0.05). Inverse correlations between lnRMSSDmean and
      lnRMSSDcv were Very Large at BL and OL (p<0.05) but only Moderate at TP (p>0.05).
      CONCLUSIONS: OL training is associated with a reduction and greater daily
      fluctuation in vagal activity compared with BL, concurrent with decrements in
      perceived fatigue and muscle soreness. These effects are reversed during TP where
      these values returned to baseline or peaked leading into successful competition.
      The strong inverse relationship between average vagal activity and its daily
      fluctuation weakened during TP.

PMID- 27890480
TI  - Chemerin-induced arterial contraction is Gi- and calcium-dependent.
AB  - Chemerin is an adipokine associated with increased blood pressure, and may link
      obesity with hypertension. We tested the hypothesis that chemerin-induced
      contraction of the vasculature occurs via calcium flux in smooth muscle cells.
      Isometric contraction of rat aortic rings was performed in parallel with calcium
      kinetics of rat aortic smooth muscle cells to assess the possible signaling
      pathway. Chemerin-9 (nonapeptide of the chemerin S157 isoform) caused a
      concentration-dependent contraction of isolated aorta (EC50 100nM) and elicited a
      concentration-dependent intracellular calcium response (EC50 10nM). Pertussis
      toxin (Gi inhibitor), verapamil (L-type Ca2+ channel inhibitor), PP1 (Src
      inhibitor), and Y27632 (Rho kinase inhibitor) reduced both calcium influx and
      isometric contraction to chemerin-9 but PD098059 (Erk MAPK inhibitor) and U73122
      (PLC inhibitor) had little to no effect on either measure of chemerin signaling.
      Although our primary aim was to examine chemerin signaling, we also highlight
      differences in the mechanisms of chemerin-9 and recombinant chemerin S157. These
      data support a chemerin-induced contractile mechanism in vascular smooth muscle
      that functions through Gi proteins to activate L-type Ca2+ channels, Src, and Rho
      kinase. There is mounting evidence linking chemerin to hypertension and this
      mechanism brings us closer to targeting chemerin as a form of therapy.

PMID- 27890481
TI  - Growth disparity of motherless children might be attributed to a deficient intake
      of high-quality nutrients.
AB  - We hypothesized that single-parent children (SPC) are retarded in growth compared
      with both-parent children (BPC), and that motherless children (MC) are affected
      differently from fatherless children. Moreover, the growth disparity between SPC
      and BPC might be attributed to a deficient nutrient intake. Data from 2967
      children between the ages of 2 and 18 years were extracted from 4 recent waves
      (2004, 2006, 2009, and 2011) of the China Health and Nutrition Survey to compare
      the growth status of SPC and BPC and to investigate the association between
      growth indicators and nutrition status. Anthropometric measures and 24-hour
      recall of 3 consecutive days of dietary intake were collected. The discrepancy of
      growth status and nutrition between BPC and SPC was analyzed by multivariable
      regression models with adjustments for socioeconomic status. Results indicated
      that MC were significantly lighter in weight than BPC (P=.03); the same trend was
      observed for height (P=.08). This might be attributed to the lower intake of
      animal-source protein (P=.02), such as meat (P=.04) and fish (P=.04). Further
      analysis showed that intake of animal-source iron and zinc was also significantly
      lower in MC compared with BPC (P=.01, P=.03). No difference was detected in
      fatherless children in comparison with BPC. Our study indicated that the loss of
      the mother adversely affected children's growth status and that a lower intake of
      animal-source protein, iron, and zinc might be a reason for the retarded growth
      status of MC.

PMID- 27890482
TI  - Dietary nitrate does not affect physical activity or outcomes in healthy older
      adults in a randomized, cross-over trial.
AB  - Although dietary nitrate (NO3-) ingestion appears to enhance exercise capacity
      and performance in young individuals, inconclusive findings have been reported in
      older people. Therefore, we conducted a double-blind, crossover randomized
      clinical trial using beetroot juice in older healthy participants, who were
      classified as normal weight and overweight. We tested whether consumption of
      beetroot juice (a rich source of NO3-) for 1 week would increase nitric oxide
      bioavailability via the nonenzymatic pathway and enhance (1) exercise capacity
      during an incremental exercise test, (2) physical capability, and (3) free-living
      physical activity. Twenty nonsmoking, healthy participants between 60 and 75
      years of age and with a body mass index of 20.0 to 29.9 kg/m2 were included.
      Presupplementation and postsupplementation resting, submaximal, maximal, and
      recovery gas exchanges were measured. Physical capability was measured by hand
      grip strength, time-up-and-go, repeated chair rising test, and 10-m walking
      speed. Free-living physical activity was assessed by triaxal accelerometry.
      Changes in urinary and plasmaNO3-concentrations were measured by gas
      chromatography-mass spectrometry. Nineteen participants (male-to-female ratio,
      9:10) completed the study.Beetroot juice increased significantly both plasma and
      urinary NO3-concentrations (P<.001) when compared with placebo. Beetroot juice
      did not influence resting or submaximal and maximal oxygen consumption during the
      incremental exercise test. In addition, measures of physical capability and
      physical activity levels measured in free-living conditions were not modified by
      beetroot juice ingestion. The positive effects of beetroot juice ingestion on
      exercise performance seen in young individuals were not replicated in healthy,
      older adults. Whether aging represents a modifier of the effects of dietary NO3
      on muscular performance is not known, and mechanistic studies and larger trials
      are needed to test this hypothesis.

PMID- 27890483
TI  - A 23 year experience with laparoscopic common bile duct exploration.
AB  - BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) during laparoscopic
      cholecystectomy (LC) is as effective as two-stage endo-laparoscopic treatment,
      but with shorter hospital stay, lower cost and recurrent stone rate. Aim of this
      paper was to report the authors' experience with LCBDE during LC. METHODS: A
      retrospective analysis of patients who underwent LCBDE for ductal stones was
      performed. Recurrent stones were defined as CBD stones detected beyond 6 months
      from the procedure. Postoperative biliary stricture was defined as a symptomatic
      reduction of CBD diameter. RESULTS: Out of 3444 patients who underwent LC, 384
      (11%) had CBD stones treated by trans-cystic duct exploration [214 (6%) patients,
      TCD-CBDE] or choledochotomy [170 (5%) patients, C-CBDE]. For TCD-CBDE and C-CBDE,
      mean operative time was 127 +/- 69 and 191 +/- 74 min, respectively. Major
      morbidity rate was 3% (n = 6) in TCD-CBDE and 6% (n = 11) in C-CBDE. The
      incidence of residual stones was 5% (n = 20) and complete ductal clearance rate
      was 95% (n = 364). After long-term follow-up (mean 189 +/- 105 months) the
      recurrent stone rate was 2%. DISCUSSION: In expert centers, LCBDE during LC is
      safe and effective with low short and long term morbidity rates.

PMID- 27890484
TI  - 25 years of advances in the definition, classification and treatment of status
      epilepticus.
AB  - PURPOSE: Status epilepticus (SE) requires not only urgent symptomatic treatment
      with antiepileptic drugs but also rapid identification and treatment of its
      cause. This narrative review summarizes the most important advances in
      classification and treatment of SE. METHOD: Data sources included MEDLINE,
      EMBASE, ClinicalTrials.gov, and back tracking of references in pertinent studies,
      reviews, and books. RESULTS: SE is now defined as "a condition resulting either
      from the failure of the mechanisms responsible for seizure termination or from
      the initiation of mechanisms, which lead to abnormally, prolonged seizures (after
      time point t1). It is a condition, which can have long-term consequences (after
      time point t2), including neuronal death, neuronal injury, and alteration of
      neuronal networks, depending on the type and duration of seizures." A new
      diagnostic classification system of SE introduces four axes: semiology,
      aetiology, EEG correlates, and age. For the acute treatment intravenous
      benzodiazepines (lorazepam, diazepam, clonazepam) and intramuscular midazolam
      appear as most effective treatments for early SE. In children, buccal or
      intranasal midazolam are useful alternatives. In established SE intravenous
      antiepileptic drugs (phenytoin, valproate, levetiracetam, phenobarbital, and
      lacosamide) are in use. Treatment options in refractory SE are intravenous
      anaesthetics; ketamine, magnesium, steroids and other drugs have been used in
      super-refractory SE with variable outcomes. CONCLUSION: Over the past 25 years
      major advances in definition, classification and understanding of its mechanisms
      have been achieved. Despite this up to 40% of patients in early status cannot be
      controlled with first line drugs. The treatment of super-refractory status is
      still an almost evidence free zone.

PMID- 27890485
TI  - Nizar Albache: championing the cause of Syrian refugees with diabetes.

PMID- 27890486
TI  - Towards a multidisciplinary approach to understand and manage obesity and related
      diseases.
AB  - Overnutrition and sedentary lifestyle result in overweight or obesity defined as
      abnormal or excessive fat accumulation that may impair health. According to the
      WHO, the worldwide prevalence of obesity nearly doubled between 1980 and 2008. In
      2008, over 50% of both men and women in the WHO European Region were overweight,
      and approximately 23% of women and 20% of men were obese. Comprehensive
      diagnostic and therapeutic approaches should include nutritional treatment to
      favor the best metabolic and nutritional outcome, as well as to induce potential
      disease-specific benefits from selected nutritional regimens. Obesity is usually
      accompanied by an increased muscle mass. This might explain why obesity, under
      particular circumstances such as cancer or high age, might have protective
      effects, a phenomenon named the 'obesity paradox'. However, loss of muscle mass
      or function can also occur, which is associated with poor prognosis and termed
      'sarcopenic obesity'. Therefore, treatment recommendations may need to be
      individualized and adapted to co-morbidities. Since obesity is a chronic systemic
      disease it requires a multidisciplinary approach, both at the level of prevention
      and therapy including weight loss and maintenance. In the present personal review
      and position paper, authors from different disciplines including endocrinology,
      gastroenterology, nephrology, pediatrics, surgery, geriatrics, intensive care
      medicine, psychology and psychiatry, sports medicine and rheumatology, both at
      the basic science and clinical level, present their view on the topic and
      underline the necessity to provide a multidisciplinary approach, to address this
      epidemic.

PMID- 27890488
TI  - Green tea, weight loss and physical activity.

PMID- 27890487
TI  - Polyphenol intake and cardiovascular risk factors in a population with type 2
      diabetes: The TOSCA.IT study.
AB  - BACKGROUND: The role of polyphenol intake on cardiovascular risk factors is
      little explored, particularly in people with diabetes. AIM: To evaluate the
      association between the intake of total polyphenols and polyphenol classes with
      the major cardiovascular risk factors in a population with type 2 diabetes.
      METHODS: Dietary habits were investigated in 2573 males and females participants
      of the TOSCA.IT study. The European Prospective Investigation on Cancer and
      Nutrition (EPIC) questionnaire was used to assess dietary habits. In all
      participants, among others, we assessed anthropometry, plasma lipids, blood
      pressure, C-reactive protein and HbA1c following a standard protocol. The USDA
      and Phenol-Explorer databases were used to estimate the polyphenol content of the
      habitual diet. RESULTS: Average intake of polyphenols was 683.3 +/- 5.8 mg/day.
      Flavonoids and phenolic acids were the predominant classes (47.5% and 47.4%,
      respectively). After adjusting for potential confounders, people with the highest
      intake of energy-adjusted polyphenols (upper tertile) had a more favorable
      cardiovascular risk factors profile as compared to people with the lowest intake
      (lower tertile) (BMI was 30.7 vs 29.9 kg/m2, HDL-cholesterol was 45.1 vs 46.9
      mg/dl, LDL-cholesterol was 103.2 vs 102.1 mg/dl, triglycerides were 153.4 vs
      148.0 mg/dl, systolic and diastolic blood pressure were respectively 135.3 vs
      134.3 and 80.5 vs 79.6 mm/Hg, HbA1c was 7.70 vs 7.67%, and C-reactive Protein was
      1.29 vs 1.25 mg/dl, p < .001 for all). The findings were very similar when the
      analysis was conducted separately for flavonoids or phenolic acids, the two main
      classes of polyphenols consumed in this population. CONCLUSIONS: Polyphenol
      intake is associated with a more favorable cardiovascular risk factors profile,
      independent of major confounders. These findings support the consumption of foods
      and beverages rich in different classes of polyphenols particularly in people
      with diabetes. CLINICAL TRIAL: http://www.clinicaltrials.gov; Study ID number:
      NCT00700856.

PMID- 27890489
TI  - Spinal Muscular Atrophy, types I and II: What are the differences in body
      composition and resting energy expenditure?
AB  - BACKGROUND & AIMS: Different neuromuscular functional domains in types I and II
      Spinal Muscular Atrophy (SMAI and SMAII) could lead to differences in body
      composition (BC) and resting energy expenditure (REE). Their identification could
      provide the key to defining appropriate strategies in clinical dietary
      management, but data comparing SMAI and SMAII in terms of BC and REE are not yet
      available. We measured total and regional fat (FM), lean (LBM), mineral (BMC)
      masses, body water (total, intra- and extra-cellular, TBW, ICW, ECW) and REE in a
      sample of SMAI and II children, matched for age and sex, and also adjusting for
      body size to compare these features of the two SMA phenotypes. METHODS: 15 SMAI
      and 15 SMAII children, (M/F = 9/6 vs 9/6, age 3.6 +/- 1.9 vs 3.5 +/- 1.8 years, p
      = 0.99), confirmed genetically, were measured as follows: Anthropometric
      measurements [Body Weight (BW), Supine Length (SL), Arm Length (AL), Femur Length
      (FL), Tibia Length (TL)], Dual x-ray Energy Absorptiometry (DEXA) [total and
      segmental FM, LBM, FFM, and BMC], Bioelectrical impedance (BIA) [TBW, ICW, ECW]
      and Indirect Calorimetry (REE, respiratory quotients) were collected by the same
      trained dietician. BW, SL and Body Mass Index (BMI) Z-scores were calculated
      according to CDC Growth Charts (2000). RESULTS: SMA children had high percentages
      of FM and a lower percentage of TBW and ECW compared to the respective reference
      values for sex and age, whereas the BMC percentages did not differ, even
      splitting the two phenotypes. SMA I children had a lower BW and BMI-Z score
      compared to children with SMA II, but similar total and segmental FM. On the
      contrary, total FFM and LBM were significantly lower in SMAI (7290.0 +/- 1729.1 g
      vs 8410.1 +/- 1508.4 g; 6971.8 +/- 1637.1 g vs 8041.7 +/- 1427.7 g, p = 0.039, p
      = 0.037, respectively), particularly at the trunk level. Arm BMC also resulted
      significantly lower in SMAI. The measured REE values were similar (684 +/- 143
      kcal/day vs 703 +/- 122 Kcal/day p = 0.707) whereas REE per FFM unit was higher
      in SMA I children than in SMA II (95 +/- 12 kcal/FFMkg vs 84 +/- 11 kcal/FFMkg p
      = 0.017). CONCLUSIONS: This study has shown that BW and BMI Z-score measurements
      alone can be misleading in assessing nutritional status, particularly in SMAI.
      The differences between SMAI and II in total and regional BC are related only to
      FFM, LBM and BMC, and seem to be more linked to the magnitude of neurofunctional
      impairment rather than to the nutritional status derangement. SMA I and SMA II
      children can have different energy requirements in relation to their specific BC
      and hypermetabolism of FFM. Based on these results, our recommendation is to use
      direct BC and REE measurements in the nutritional care process until SMA-specific
      predictive equations become available.

PMID- 27890490
TI  - Fragmentation of daily rhythms associates with obesity and cardiorespiratory
      fitness in adolescents: The HELENA study.
AB  - BACKGROUND & AIMS: Chronobiology studies periodic changes in living organisms and
      it has been proposed as a promising approach to investigate obesity. We analyze
      the association of the characteristics of the rest-activity rhythms with obesity,
      cardiorespiratory fitness and metabolic risk in adolescents from nine European
      countries. METHODS: 1044 adolescents (12.5-17.5 y) were studied. Circadian health
      was evaluated by actigraphy with accelerometers (Actigraph GT1M). Characteristics
      of the daytime activity such as fragmentation (intradaily variability), estimated
      acrophase, and 10 h mean daytime activity index were obtained. Body composition
      was assessed using Bioelectrical-Impedance-Analysis, skinfold thickness, air
      displacement-plethysmography and Dual-energy-X-ray-Absorptiometry.
      Cardiorespiratory fitness (VO2max) and metabolic risk were studied. RESULTS:
      Highly fragmented activity rhythms were associated with obesity and central
      adiposity (P < 0.05). Obese adolescents had ~3 times higher odds of having a high
      fragmentation of daytime activity compared to normal weight adolescents OR (95%
      CI) = 2.8 (1.170, 6.443). A highly fragmented rhythm was also related to lower
      cardiorespiratory fitness and higher metabolic risk (P < 0.05) so those
      adolescents classified as low fitness showed a significantly higher fragmentation
      of daytime activity than those included in the high fitness group (P < 0.0001).
      Other characteristics of the rhythms such as smaller 10 h daytime mean activity
      index and delayed estimated acrophase were also related to obesity and metabolic
      risk (P < 0.05). CONCLUSIONS: Our results indicate that the daily organization of
      the rest-activity cycle is more fragmented in obese and less fit adolescents and
      correlates with higher metabolic risk. This fact reinforces our hypothesis that
      disturbances in daily rhythms can be considered as sensitive markers of poorer
      adolescent's health.

PMID- 27890491
TI  - Neural pattern similarity between contra- and ipsilateral movements in high
      frequency band of human electrocorticograms.
AB  - The cortical motor areas are activated not only during contralateral limb
      movements but also during ipsilateral limb movements. Although these ipsilateral
      activities have been observed in several brain imaging studies, their functional
      role is poorly understood. Due to its high temporal resolution and low
      susceptibility to artifacts from body movements, the electrocorticogram (ECoG) is
      an advantageous measurement method for assessing the human brain function of
      motor behaviors. Here, we demonstrate that contra- and ipsilateral movements
      share a similarity in the high-frequency band of human ECoG signals. The ECoG
      signals were measured from the unilateral sensorimotor cortex while patients
      conducted self-paced movements of different body parts, contra- or ipsilateral to
      the measurement side. The movement categories (wrist, shoulder, or ankle) of
      ipsilateral movements were decoded as accurately as those of contralateral
      movements from spatial patterns of the high-frequency band of the precentral
      motor area (the primary motor and premotor areas). The decoder, trained in the
      high-frequency band of ipsilateral movements generalized to contralateral
      movements, and vice versa, confirmed that the activity patterns related to
      ipsilateral limb movements were similar to contralateral ones in the precentral
      motor area. Our results suggest that the high-frequency band activity patterns of
      ipsilateral and contralateral movements might be functionally coupled to control
      limbs, even during unilateral movements.

PMID- 27890492
TI  - Treatment of leydig cell tumours of the testis: Can testis-sparing surgery
      replace radical orchidectomy? Results of a systematic review.
AB  - INTRODUCTION: The gold standard for Leydig cell tumours (LCTs) is still
      considered radical orchidectomy, but testis sparing surgery (TSS) in conjunction
      with intraoperative frozen section (FSE) has been recently attempted with
      promising results. ACQUISITION OF EVIDENCE: Studies were identified by searching
      electronic databases. A bibliographic search covering the period from January
      1980 to December 2012 was conducted using PubMed/MEDLINE and EMBASE database.
      Studies were excluded if they were single case reports, meeting abstracts and
      conference proceedings. SYNTHESIS OF EVIDENCE: The present analysis is based on a
      total of 13 studies that fulfilled the predefined inclusion criteria. A total of
      247 participants were included in the 13 studies examined in this systematic
      review. 145 were treated with radical orchiectomy and 102 with TSS. In the
      radical surgery group, the follow-up varied from 6 to 249 months). In the TSS
      group, the follow-up varied from 6 to 192 months. Frozen section was performed in
      a total of 96 patients. Sensitivity was 87.5%. None of the patients treated with
      TSS presented a metastatic recurrence, while in patients treated with radical
      orchiectomy three patients presented with metastatic recurrence In selected cases
      radical surgery appears excessive and the potential for a shift to TSS as the
      standard management is gathering momentum. CONCLUSIONS: The results confirm the
      favourable course of LCT treated with TSS. The results obtained are encouraging
      and the concept is attractive to become the standard therapy in all patients and
      not only in people affected by (sub)fertility or with solitary testis.

PMID- 27890493
TI  - Higher number of transrectal ultrasound guided prostate biopsy cores is
      associated with higher blood loss and perioperative complications in robot
      assisted radical prostatectomy.
AB  - INTRODUCTION: The local inflammatory process after prostate biopsies can have a
      negative impact on functional outcomes of radical prostatectomy. There is no
      evidence in literature demonstrating its impact on radical prostatectomy.
      OBJECTIVES: To evaluate the impact of the number of TRUS core biopsies in the
      surgical morbidity and rate of positive margin on robot assisted radical
      prostatectomy (RARP). MATERIAL AND METHODS: A prospectively maintained database
      of 2,054 RARPs in a single institution. Patients were further grouped into 2
      groups based on the number of TRUS biopsy cores (G1<=12 cores; G2>12 cores).
      Multivariable logistic regression model was applied to analyze the impact of
      number of cores on complications. RESULTS: A total number of 1,042 patients in
      the group 1 (<=12 cores) and 1,012 patients in the group 2 (>12 cores) were
      included. The rate of perioperative complications increased with higher number of
      biopsies (G1 6.4 vs. G2 8.5%; P=.03), but high grade complication (Clavien 3-4)
      were similar (G1 1.4 vs. G2 2.2%; P=.16). Positive surgical margin rates were
      similar in both groups (G1 11.8 vs. 9.98%; P=.2). At the multivariable logistic
      regression analysis shown that G2 had a 39% (OR 0.645) higher rate to experience
      perioperative complications during RARP. CONCLUSION: Higher number of TRUS biopsy
      cores (>12) is associated to higher blood loss and perioperative complications
      during RARP. Careful preoperative evaluation for those patients underwent
      multiple biopsies or saturation protocols is mandatory. Application of longer
      intervals (>6 weeks) between biopsy and surgery may be advisable to minimize
      potential risks of surgical complications in patients may benefit from RARP.
      Further studies are still necessary to confirm these results.

PMID- 27890494
TI  - Neuroendocrine Tumors of the Lung: Current Challenges and Advances in the
      Diagnosis and Management of Well-Differentiated Disease.
AB  - Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that
      arise from neuroendocrine cells throughout the body, most commonly originating
      from the lungs and gastrointestinal tract. Lung NETs can be classified as well
      differentiated (low-grade typical carcinoids [TCs] and intermediate-grade
      atypical carcinoids [ACs]) and poorly differentiated (high-grade large cell
      neuroendocrine carcinoma or SCLC). The incidence of these tumors is increasing,
      but disease awareness remains low among thoracic specialists, who are often
      involved in the diagnosis and early treatment for these patients. An accurate and
      timely diagnosis can ensure the implementation of appropriate treatment and have
      a substantial impact on prognosis. However, lung NET classification and
      diagnosis, particularly for TCs/ACs, are complicated by several factors,
      including a variable natural history and nonspecific symptoms. Surgery remains
      the only curative option for TCs/ACs, but there is a lack of consensus between
      lung NET management guidelines regarding optimal treatment approaches in the
      unresectable/metastatic setting on account of the limited availability of high
      level clinical evidence. As a result, a multidisciplinary approach to management
      of lung NETs is required to ensure a consistent and optimal level of care.
      RADIANT-4 is the first phase III trial involving a large subpopulation of
      patients with advanced well-differentiated lung NETs to report reductions in the
      risk for disease progression and death with everolimus over placebo. This led to
      the recent U.S. approval of everolimus-the first agent approved for advanced lung
      TCs/ACs. To further improve evidence-based care, additional randomized controlled
      trials in patients with lung carcinoids are needed.

PMID- 27890495
TI  - Critical care guidelines-more science less art?

PMID- 27890496
TI  - Chronic cough and cough hypersensitivity syndrome.

PMID- 27890497
TI  - Care for ARDS in 2016: room to improve.

PMID- 27890499
TI  - Bronchiectasis in 2016: advances in our understanding.

PMID- 27890498
TI  - Asthma in 2016: reassured about the old, excited about the new.

PMID- 27890500
TI  - COPD in 2016: some answers, more questions.

PMID- 27890501
TI  - Cystic fibrosis in 2016: considerable progress, but much more to do.

PMID- 27890502
TI  - IPF in 2016: towards a better diagnosis.

PMID- 27890503
TI  - Lung cancer in 2016: immunotherapy comes of age.

PMID- 27890504
TI  - Pneumonia in 2016: towards better care.

PMID- 27890505
TI  - The death of Madame Tussaud: a cardiorespiratory interpretation.

PMID- 27890506
TI  - Serum procalcitonin and the admission decision in CAP.

PMID- 27890508
TI  - Corrections.

PMID- 27890507
TI  - Response to "Extremis: a sensitive look at life (and death) in the ICU".

PMID- 27890509
TI  - Small-scale screening method for low-viscosity antibody solutions using small
      angle X-ray scattering.
AB  - In this study, we investigated the concentration range in which self-association
      starts to form in humanized IgG monoclonal antibody (mAb) solutions. Furthermore,
      on the basis of the results, we developed a practical method of screening for low
      viscosity antibody solutions by using small-angle X-ray scattering (SAXS)
      measurements utilizing small quantities of samples. With lower-viscosity mAb3,
      self-association was not detected in the range of 1-80mg/mL. With higher
      viscosity mAb1, on the other hand, self-association was detected in the range of
      10-20mg/mL and was clearly enhanced by a decrease in temperature. The viscosities
      of mAb solutions at 160, 180, and 200mg/mL at 25 degrees C quantitatively
      correlated very well with the particle size parameters obtained by SAXS
      measurements of mAb solutions at 15mg/mL at 5 degrees C. The quantity of mAb
      sample required for the SAXS measurements was only 0.15mg, which is about one
      hundredth of that required for actual viscosity measurements at a high
      concentration, and such quantities could be available even at an early stage of
      development. In conclusion, the SAXS analysis method proposed in this study is a
      valuable tool for the development of concentrated mAb therapeutics with high
      manufacturability and high usability for subcutaneous injection.

PMID- 27890510
TI  - In situ forming pluronic(r) F127/chitosan hydrogel limits metronidazole
      transmucosal absorption.
AB  - The objective of this work is to design topically-applied thermosensitive and
      mucoadhesive hydrogel containing metronidazole (MTZ) for the treatment of
      Trichomonas vaginalis infections. Hydrogel composed of pluronic(r) F127 (20wt%),
      chitosan (1wt%) and metronidazole MTZ (0.7wt%) mixture showed its ability to
      decrease by a factor 4 MTZ flux and apparent permeability absorption through
      vaginal mucosa. The impact of hydrogel on transmucosal penetration of MTZ was
      evaluated ex vivo on excised porcine vaginal mucosa mounted on Franz diffusion
      cell. The anti-T. vaginalis activity of MTZ formulated into F127/chitosan
      hydrogel was preserved since the viability curve evaluated in vitro was similar
      to MTZ solution.

PMID- 27890511
TI  - Cuticular microstructures turn specular black into matt black in a stick insect.
AB  - The stick insect Peruphasma schultei stands out from other insects by its deep
      matt black cuticle. We tested whether the appearance of P. schultei is due to
      microstructures of the cuticle, a phenomenon that has recently been described for
      the velvet black scales of the Gaboon viper. The shiny black stick insect
      Anisomorpha paromalus served as a control. We found that the P. schultei cuticle
      is characterised by two different types of microstructures, tall elevations with
      a maximum size of 18 MUm and small structures with a height of 4 MUm. Other than
      in the snake, P. schultei microstructures do not bear nanostructures. The
      microstructures scatter light independently of the viewing angle. This causes the
      matt appearance of the cuticle, whereas pigments are responsible for the black
      colouration, resulting in a maximum reflectance of 2.8% percent. The
      microstructures also cause the hydrophobic properties of the cuticle with contact
      angles near 130 degrees . Resin replicas and bleaching of the cuticle strongly
      support these results. Moreover, the matt black cuticle has a higher heat
      absorption compared to the control. We discuss the selective benefit of the matt
      black appearance of P. schultei in the context of behaviour, ecology and
      phylogeny.

PMID- 27890512
TI  - Safety and efficacy of valve repositioning during transcatheter aortic valve
      replacement with the Lotus Valve System.
AB  - OBJECTIVE: To determine the safety and efficacy of valve repositioning following
      transcatheter aortic valve replacement (TAVR) with the Lotus Valve System (Boston
      Scientific, Marlborough, MA, USA). INTRODUCTION: TAVR is a well-established
      treatment for severe aortic stenosis. The Lotus Valve System is fully
      repositionable and retrievable. Valve repositioning has the potential to minimize
      TAVR-related complications caused by valve malposition; however, the effect on
      adverse event rates such as stroke is unknown. METHODS: Consecutive patients with
      severe aortic stenosis treated with the Lotus Valve System (n=125) were
      prospectively recruited. Patients who did not require valve repositioning (Group
      A) were compared to patients who required one or more valve repositions (Group
      B). The primary end-point was 30-day occurrence of major adverse cardiovascular
      and cerebrovascular events (MACCE). Secondary end-points included each component
      of the primary end-point, new pacemaker insertion, and procedural or 30-day major
      adverse events, defined according to VARC-2 definitions. RESULTS: Valve
      repositioning was utilized in 60.8% (76/125) of patients including 17.1% (13/76)
      who required full valve resheathing. The most frequent indications for valve
      repositioning were altering the depth and angulation of initial implantation
      (69.7%), reducing paravalvular regurgitation (13.2%), and attempt to correct new
      or worsened heart block (7.9%). Baseline characteristics were similar in both
      groups. The primary end-point occurred in 12.2% and 6.6% of Group A and B,
      respectively (p=0.10). Thirty-day new pacemaker implantation was 34.1% and 18.8%
      in Group A and B, respectively (p=0.06). The secondary end-point measures were
      not significantly different between the groups. CONCLUSION: Repositioning
      facilitated correct anatomical positioning of all devices leading to optimal
      prosthesis hemodynamics and a trend to lower pacemaker rate without increased
      risk of MACCE.

PMID- 27890513
TI  - Therapeutic effect of immunoadsorption and subsequent immunoglobulin substitution
      in patients with dilated cardiomyopathy: Results from the observational
      prospective Bad Berka Registry.
AB  - BACKGROUND: Elimination of cardiac autoantibodies, frequently detected in
      patients with dilated cardiomyopathy (DCM), with immunoadsorption (IA) improves
      functional capacity and left ventricular (LV) function. This study aimed to
      prospectively address this issue in a large cohort of unselected patients.
      METHODS: Consecutive patients undergoing IA followed by IgG substitution were
      included. Clinical and echocardiographic parameters were assessed at baseline
      (BL) and 12-month follow-up (FU). Patients were classified as IA responders when
      >=2 of the following criteria were achieved: improvement in the Minnesota Living
      with Heart Failure Questionnaire (MLHFQ) >=5 points, symptoms [>=1 New York Heart
      Association (NYHA) class], LV ejection fraction (EF) >=10% or decrease in LV end
      diastolic diameter (EDD) >=10%, or N-terminal pro B-type natriuretic peptide (NT
      pro-BNP) >=50%. RESULTS: 93 patients (median age 61 years, LVEF 30%, duration of
      symptoms 14 months, 87% in NYHA class III/IV, >90% treated with beta
      blocker/angiotensin-converting enzyme inhibitor) were included. When the entire
      cohort was analyzed, a significant improvement in MLHFQ (50 vs. 26 points), NYHA
      class (median 3.0 vs. 2.0), LVEF (30% vs. 38%), LVEDD (62 vs. 59mm), NT-pro-BNP
      (892 vs. 523pg/ml) was observed at FU (p<0.05 for all). 48% (n=43) were
      classified as responders. Those were characterized by a shorter disease duration
      (11 vs. 22 months), larger BL LVEDD (64 vs. 60mm), presence of >1 viral genome,
      and higher values of mononuclear inflammatory cells at endomyocardial biopsy.
      Sixteen (17.2%) patients experienced IA related complications. CONCLUSIONS: A
      positive response is observed in 48% of inflammatory DCM patients undergoing IA,
      and this translates into a significant improvement in clinical and
      echocardiographic parameters.

PMID- 27890515
TI  - Patterns of Waterpipe Tobacco Smoking Among U.S. Young Adults, 2013-2014.
AB  - INTRODUCTION: Patterns of waterpipe smoking and associated other tobacco use were
      assessed among U.S. young adults (aged 18-24 years). METHODS: A descriptive
      analysis of baseline data (2013-2014) from the Population Assessment of Tobacco
      and Health Study was conducted in 2016. RESULTS: The study included 9,119 young
      adults-44% ever and 11% past-30 day waterpipe smokers (12% of men and 9% of women
      were past-30 day smokers). Among past-30 day smokers, waterpipe smoking frequency
      was distributed as follows: 4% daily, 23% weekly, 36% monthly, and 37% less than
      monthly. The average session exceeded 30 minutes for 79% of respondents. In this
      age group, 29% were exclusive waterpipe smokers, 16% were dual
      (waterpipe/cigarette) smokers, 8% were dual (waterpipe/e-cigarette) users, 19%
      were waterpipe/cigarette/e-cigarette users, and 28% presented with other
      combinations of poly use. CONCLUSIONS: Waterpipe smoking is widespread among U.S.
      young adults. Although waterpipe patterns are predominantly intermittent, the
      average smoking session provides prolonged exposure. Waterpipe smoking among
      young adults is primarily characterized by the use of flavored tobacco, the cafe
      culture, and poly tobacco use. Rising trends in waterpipe smoking among U.S.
      youth warrant a strong regulatory response to prevent future waterpipe-related
      morbidity and mortality.

PMID- 27890514
TI  - Effectiveness of radiolabelled somatostatin analogues (90Y-DOTATOC and 177Lu
      DOTATATE) in patients with metastatic neuroendocrine tumours: a single centre
      experience in Mexico.
AB  - OBJECTIVE: To determine the effectiveness of therapy with the radiolabelled
      somatostatin analogues, 90Y-DOTATOC and 177Lu-DOTATATE, in the treatment of
      metastatic neuroendocrine tumours with progression to first-line treatment.
      MATERIAL AND METHODS: A study was conducted on 30 patients diagnosed with
      neuroendocrine tumours (gastroenteropancreatic, bronchopulmonary, MEN2A, MEN2B,
      phaeochromocytoma, and paraganglioma) with metastatic disease diagnosed by the
      pathology department, with progression to first-line treatment, and recruited
      from December 2014 to February 2016. Efficacy was analysed using computed
      tomography (CT) according RECIST 1.1 criteria, and the molecular changes using
      the SUVmax of PET/CT with 68Ga-DOTATOC. Safety was carried out with a renal scan
      with 99mTc-MAG3. RESULTS: The 30 patients received a total of 49 cycles 90Y
      DOTATOC (21 doses) and 177 Lu-DOTATATE (28 doses), with a mean of 1.5 cycles per
      patient. Of these, 17 (56.7%) showed a partial morphological response, 22 (73.3%)
      molecular and biochemical response, and 23 (76.6%) clinical response. One patient
      died during the median follow-up of 13 months. The median overall survival from
      diagnosis was 54 months (95% CI; 31.18-76.81), and median progression-free
      survival was 32 months (95% CI; 15.00-48.99). CONCLUSION: Therapy with 90Y
      DOTATOC and 177Lu-DOTATATE is a promising therapy for patients with well and
      moderately differentiated neuroendocrine tumours. The efficacy is better the
      larger the number of cycles administered, inversely proportional to the number of
      metastases (<10), and is associated with the level of uptake according to the
      SUVmax by the metastases, regardless of metabolically active tumour volume.

PMID- 27890516
TI  - Trends in E-Cigarette Awareness and Perceived Harmfulness in the U.S.
AB  - INTRODUCTION: Electronic cigarettes (e-cigarettes) are gaining in popularity as
      an alternative to regular cigarettes, as they are viewed as potentially less
      harmful. However, it remains unclear how awareness about e-cigarettes is
      permeating through the general U.S. POPULATION: This study seeks to extend
      previous research and examine trends in e-cigarette awareness and perceived
      harmfulness, and their association with smoking-cessation efforts. METHODS: Data
      from three cycles (2012, 2013, and 2014) of the Health Information National
      Trends Survey were combined into a single data set. Controlling for survey year,
      multivariate logit models were used to determine the association between
      demographic characteristics and e-cigarette awareness, perceived harmfulness,
      quit attempts, and quit intentions. Data were analyzed in 2015. RESULTS:
      Awareness of e-cigarettes increased from 77.1% in 2012 to 94.3% in 2014.
      Controlling for demographic characteristics, e-cigarette awareness significantly
      increased in both 2013 and 2014, relative to 2012. Perception that e-cigarettes
      were less harmful than regular cigarettes declined from 50.7% in 2012 to 43.1% in
      2014. Among smokers, no relationship was observed between e-cigarette awareness
      and past-year quit attempts or quit intentions, but those that viewed e
      cigarettes as less harmful were less likely to have a past-year quit attempt.
      CONCLUSIONS: These analyses reveal a continued increase in overall public
      awareness of e-cigarettes and shifting harm perceptions relative to regular
      cigarettes. New regulatory oversight by the U.S. Food and Drug Administration may
      have major effects on both dimensions, which are worth continued monitoring.

PMID- 27890517
TI  - Correlates of Receiving a Recommendation for More Physical Activity From a
      Primary Care Provider.
AB  - INTRODUCTION: Primary care providers (PCPs) are strategically positioned to
      communicate with their overweight/obese patients about positive behavioral
      changes to improve health and functioning. Demographic and behavioral correlates
      of receiving a recommendation for more physical activity (PA) from a PCP by
      overweight/obese patients were assessed. METHODS: Community-dwelling adults aged
      >=50 years from four Texas cities who were seen by a family physician in a
      primary care clinic were surveyed from October 2013 to June 2014. Multivariate
      logistic regression predicted the likelihood of receiving a PA recommendation
      from a PCP, controlling for sociodemographic factors, health conditions, and
      walking behaviors. The analysis was conducted in 2016. RESULTS: Of the total 388
      participants (survey response rate, 6.8%), 30.1% were obese, 55.4% were female,
      and most were non-Hispanic white (82.9%), married (75.6%), or reported an annual
      household income of >=$50,000 (66.8%). Receipt of a PA recommendation from a PCP
      (n=151, 38.9%) was significantly correlated with reporting poor to fair health
      (OR=7.33, 95% CI=2.6, 20.32), obesity (OR=2.95, 95% CI=1.69, 5.14), having only a
      little or some difficulty walking for a quarter of a mile (OR=2.94, 95% CI=1.41,
      5.88), not walking the recommended >=150 minutes for any purpose (OR=2.60, 95%
      CI=1.25, 5.38), and being employed (OR=2.11, 95% CI=1.13. 3.94). CONCLUSIONS:
      PCPs seem to be targeting obese, inactive individuals with poor to fair health,
      populations traditionally not encouraged to be more physically active. These
      findings are consistent with the current trend in medical care to recommend
      positive lifestyle changes to a broader range of the population.

PMID- 27890518
TI  - A Comparison of Parent- and Provider-Reported Human Papillomavirus Vaccination of
      Adolescents.
AB  - INTRODUCTION: There is considerable effort at the state and national levels to
      monitor human papillomavirus (HPV) vaccine uptake and understand the factors that
      influence who gets vaccinated. Accurate measurement of vaccination coverage is
      critical for monitoring HPV vaccination. This study aimed to determine
      comparability between parent- and provider-reported HPV vaccination status for a
      sample of adolescents in the U.S. METHODS: Data from the 2014 National
      Immunization Survey-Teen were analyzed in 2016 for 20,827 adolescents.
      Information on HPV vaccine uptake (initiation [one or more dose] and completion
      [three or more doses]) was obtained using parental (recall) and provider reports
      (electronic medical records). Sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and kappa-coefficient were computed to
      determine how comparable parental and provider (ref group) reports were for HPV
      vaccination. RESULTS: Prevalence of HPV vaccine initiation was comparable between
      parental and provider report (51.3% vs 50.0%) and for completion (30.7% vs
      27.3%). Compared with provider report, parent-reported HPV vaccine initiation had
      high sensitivity (86.0%), specificity (87.4%), PPV (87.5%), NPV (85.9%), and
      acceptable kappa-coefficient (0.73). Compared with provider report, parent
      reported HPV vaccine completion had a sensitivity of 71.5%, specificity of 91.1%,
      PPV of 78.5%, NPV of 87.6%, and kappa-coefficient of 0.64. Similar
      characteristics-adolescent age, sex, number of doctor visits, and region-were
      associated with HPV vaccine uptake using parental and provider reports.
      CONCLUSIONS: Parental recall is comparable to provider report in monitoring HPV
      vaccine uptake for adolescents, although parental recall is less comparable for
      HPV vaccine completion.

PMID- 27890519
TI  - Helping People to Self-Actualize: Revising the Role and Goal of Our Healthcare
      System.

PMID- 27890520
TI  - Is Friendship Limited? An Inquiry Into Dunbar's Number.

PMID- 27890521
TI  - Financial incentives for diabetes prevention in a Medicaid population: Study
      design and baseline characteristics.
AB  - BACKGROUND: Medicaid beneficiaries at high risk for diabetes can benefit from the
      Diabetes Prevention Program (DPP) lifestyle intervention. The We Can Prevent
      Diabetes (WCPD) trial examined whether financial incentives are more effective
      than no financial incentives in sustaining participation in the DPP and
      increasing weight loss. Here we describe the study design and baseline
      characteristics. METHODS: The WCPD was a 3-arm group-randomized controlled trial.
      Medicaid beneficiaries were aged 18 to 74years, had prediabetes or gestational
      diabetes, and were overweight or obese. Subjects enrolled from 13 primary care
      clinics into groups of 8 to 15 participants. Participants received the 12-month
      DPP delivered by the YMCA or trained clinic staff, free of costs. Participants
      from groups randomized into the intervention conditions were eligible to receive
      incentives up to $520 by attending sessions and meeting weight loss goals.
      RESULTS: The WCPD enrolled 1154 participants into 98 groups. Among the 847
      attending at least one DPP session, 71.2% were women; the mean age was 48.3years;
      79.3% were obese; and 87.6% entered the study with an elevated HbA1c or fasting
      plasma glucose. Participants' primary languages were Somali (21.0%), Hmong
      (3.1%), Spanish (2.2%), or English (72.4%). CONCLUSIONS: The WCPD trial
      demonstrated that a collaborative approach with primary care clinics and the YMCA
      can efficiently identify, enroll, and deliver the 12-month DPP to Medicaid
      beneficiaries. If the WCPD incentive arms increase attendance and weight loss,
      the use of financial incentives may be an avenue for engaging low-income, high
      risk patients in lifestyle change.

PMID- 27890522
TI  - Design and challenges of a randomized clinical trial of medical expulsive therapy
      (tamsulosin) for urolithiasis in the emergency department.
AB  - Urolithiasis or urinary stone disease has been estimated to affect about 1 in 11
      Americans. Patients with urinary stone disease commonly present to the emergency
      department for management of their acute pain. In addition to providing
      analgesia, administration of drug (medical expulsive therapy) is often prescribed
      to assist passage of the urinary stone. In this methodology paper, we describe
      the design of a prospective, multi-center, randomized, double-blind placebo
      controlled clinical trial of the alpha-adrenergic blocker, tamsulosin, to
      evaluate its effectiveness as medical expulsive therapy. In addition, we describe
      the unique challenges of conducting a trial of this type within the setting of
      the emergency department.

PMID- 27890523
TI  - Fenestrated Endovascular Aneurysm Repair of a Stent Graft-induced New Entry Tear
      in a Patient with a Celiacomesenteric Trunk.

PMID- 27890524
TI  - The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular
      Disease in Men and Women Aged 65-74 Years.
AB  - OBJECTIVE/BACKGROUND: This pilot study of a large population based randomised
      screening trial investigated feasibility, acceptability, and relevance
      (prevalence of clinical and subclinical cardiovascular disease [CVD] and
      proportion receiving insufficient prevention) of a multifaceted screening for
      CVD. METHODS: In total, 2060 randomly selected Danish men and women aged 65-74
      years were offered (i) low dose non-contrast computed tomography to detect
      coronary artery calcification (CAC) and aortic/iliac aneurysms; (ii) detection of
      atrial fibrillation (AF); (iii) brachial and ankle blood pressure measurements;
      and (iv) blood levels of cholesterol and hemoglobin A1c. Web based self booking
      and data management was used to reduce the administrative burden. RESULTS:
      Attendance rates were 64.9% (n = 678) and 63.0% (n = 640) for men and women,
      respectively. In total, 39.7% received a recommendation for medical preventive
      actions. Prevalence of aneurysms was 12.4% (95% confidence interval [CI] 9.9
      14.9) in men and 1.1% (95% CI 0.3-1.9) in women, respectively (p < .001). A CAC
      score > 400 was found in 37.8% of men and 11.3% of women (p < .001), along with a
      significant increase in median CAC score with age (p = .03). Peripheral arterial
      disease was more prevalent in men (18.8%, 95% CI 15.8-21.8) than in women (11.2%,
      95% CI 8.7-13.6). No significant differences between the sexes were found with
      regard to newly discovered AF (men 1.3%, women 0.5%), potential hypertension (men
      9.7%, women 11.5%), hypercholesterolemia (men 0.9%, women 1.1%) or diabetes
      mellitus (men 2.1%, women 1.3%). CONCLUSION: Owing to the higher prevalence of
      severe conditions, such as aneurysms and CAC >= 400, screening for CVD seemed
      more prudent in men than women. The attendance rates were acceptable compared
      with other screening programs and the logistical structure of the screening
      program proved successful.

PMID- 27890525
TI  - After Superficial Ablation for Superficial Reflux Associated with Primary Deep
      Axial Reflux, Can Variable Outcomes be Caused by Deep Venous Valve Anomalies?
AB  - OBJECTIVE: To identify which deep anatomical anomalies can explain variable
      hemodynamic outcomes in patients with superficial reflux associated with primary
      deep axial reflux who underwent isolated superficial vein ablation without
      improvement. METHODS: This is a retrospective study of deep venous valve
      anomalies in patients who underwent superficial vein ablation for superficial and
      associated deep reflux. A group of 21 patients who were diagnosed with saphenous
      reflux associated with primary deep axial reflux, were submitted to great
      saphenous vein ablation. In 17 patients the deep reflux was not abolished. In
      this subgroup, surgical exploration of the deep valve was carried out using
      venotomy for possible valve repair. RESULTS: Among the 17 subgroup patients, four
      post-thrombotic lesions were discovered intra-operatively in four patients; they
      underwent different surgical procedures. In 13 of the subgroup patients, primary
      valve incompetence was confirmed intra-operatively. In 11 cases the leaflets were
      asymmetrical and in only two were they symmetrical. After valvuloplasty, deep
      reflux was abolished in all 13 patients. Clinical improvement was obtained in
      12/13 patients (92%). It is noteworthy that abolition of deep reflux was
      associated with significant improvement in air plethysmography data as well as
      with improvement in clinical status measured on CEAP class, VCSS and the SF-36
      questionnaire. CONCLUSION: Failure to correct deep axial reflux by superficial
      ablation in patients with superficial and associated primary deep axial reflux
      may be related to asymmetry in the leaflets of the incompetent deep venous valve.

PMID- 27890526
TI  - Femoropopliteal In-stent Restenosis Repair: Midterm Outcomes After Paclitaxel
      Eluting Balloon Use (PLAISIR Trial).
AB  - OBJECTIVE: The aim was to assess 18 month outcomes of the paclitaxel eluting
      balloon (PEB) in patients with femoropopliteal (FP) in-stent restenosis (ISR).
      METHODS: In a national prospective and multicentre cohort study, symptomatic
      patients with femoropopliteal in-stent restenosis were included from January 2012
      to June 2013. Patients were treated by paclitaxel eluting balloon angioplasty (In
      Pact Admiral, Medtronic, Santa Rosa, CA, USA). Clinical and duplex scan follow-up
      evaluations were performed at 1, 3, 6, 9, 12, and 18 months. The primary endpoint
      was freedom from target lesion revascularisation (TLR) at 12 months. Secondary
      endpoints were major adverse cardiovascular events (MACE), Target extremity
      revascularisation (TER), primary and secondary sustained clinical improvement,
      recurrent restenosis rate, primary and secondary patency, quality of life
      assessed by EQ-5D questionnaire, technical success, clinical success, and length
      of stay RESULTS: A total of 53 patients were enrolled. After a blinded review, 10
      patients were defined as protocol violation because restenosis occurred more than
      2 years after stent implantation. Procedures were performed in 55 limbs, 48 (87%)
      for claudication and 7 (13%) for critical limb ischaemia. The mean diameter and
      length of PEB were 6 +/- 0.57 mm and 86 mm +/- 32 mm, follow-up was 17 months
      (range 1-19). At 1 year, the survival rate was 96 +/- 2.7% and freedom from TLR
      and TER were 90.2 +/- 4.2% and 85 +/- 5%, respectively. Sustained primary and
      secondary clinical improvements were 78.6 +/- 5.7% and 92.0 +/- 3.8%,
      respectively. At 1 year, the primary patency rate was 83.7 +/- 5.0%. Prior to the
      procedure, the mean EQ-5D score was 66 +/- 14 and 74 +/- 16 at 1 year (p = .10).
      Two patients died during follow-up; one patient died 33 days after the procedure
      because of limb ischaemia. CONCLUSION: PEB for the treatment of FP ISR is
      associated with a low rate of re-interventions and restenosis. Clinical
      improvement is maintained at 18 months.

PMID- 27890527
TI  - Personalized Perioperative Pediatric Pain Management: Myth or Reality?

PMID- 27890528
TI  - Pathological concentration of zinc dramatically accelerates abnormal aggregation
      of full-length human Tau and thereby significantly increases Tau toxicity in
      neuronal cells.
AB  - A pathological hallmark of Alzheimer disease and other tauopathies is the
      formation of neurofibrillary tangles mainly composed of bundles of fibrils formed
      by microtubule-associated protein Tau. Here we study the effects of Zn2+ on
      abnormal aggregation and cytotoxicity of a pathological mutant DeltaK280 of full
      length human Tau. As revealed by Congo red binding assays, transmission electron
      microscopy, immunofluorescence, Western blot, and immunogold electron microscopy,
      pathological concentration of Zn2+ dramatically accelerates the fibrillization of
      DeltaK280 both in vitro and in SH-SY5Y neuroblastoma cells. As evidenced by
      annexin V-FITC apoptosis detection assay and MTT reduction assay, pathological
      concentration of Zn2+ remarkably enhances DeltaK280 fibrillization-induced
      apoptosis and toxicity in SH-SY5Y cells. Substitution of Cys-291 and Cys-322 with
      Ala, however, essentially eliminates such enhancing effects of Zn2+ on the
      fibrillization and the consequent cytotoxicity of DeltaK280. Furthermore, Zn2+ is
      co-localized with and highly enriched in amyloid fibrils formed by DeltaK280 in
      SH-SY5Y cells. The results from isothermal titration calorimetry show that Zn2+
      binds to full-length human Tau by interacting with Cys-291 and Cys-322, forming a
      1:1 Zn2+-Tau complex. Our data demonstrate that zinc dramatically accelerates
      abnormal aggregation of human Tau and significantly increases Tau toxicity in
      neuronal cells mainly via bridging Cys-291 and Cys-322. Our findings could
      explain how pathological zinc regulates Tau aggregation and toxicity associated
      with Alzheimer disease.

PMID- 27890529
TI  - Mass spectrometry analysis shows the biosynthetic pathways supported by pyruvate
      carboxylase in highly invasive breast cancer cells.
AB  - We recently showed that the anaplerotic enzyme pyruvate carboxylase (PC) is up
      regulated in human breast cancer tissue and its expression is correlated with the
      late stages of breast cancer and tumor size [Phannasil et al., PloS One 10,
      e0129848, 2015]. In the current study we showed that PC enzyme activity is much
      higher in the highly invasive breast cancer cell line MDA-MB-231 than in less
      invasive breast cancer cell lines. We generated multiple stable PC knockdown cell
      lines from the MDA-MB-231 cell line and used mass spectrometry with 13C6-glucose
      and 13C5-glutamine to discern the pathways that use PC in support of cell growth.
      Cells with severe PC knockdown showed a marked reduction in viability and
      proliferation rates suggesting the perturbation of pathways that are involved in
      cancer invasiveness. Strong PC suppression lowered glucose incorporation into
      downstream metabolites of oxaloacetate, the product of the PC reaction, including
      malate, citrate and aspartate. Levels of pyruvate, lactate, the redox partner of
      pyruvate, and acetyl-CoA were also lower suggesting the impairment of
      mitochondrial pyruvate cycles. Serine, glycine and 5-carbon sugar levels and flux
      of glucose into fatty acids were decreased. ATP, ADP and NAD(H) levels were
      unchanged indicating that PC suppression did not significantly affect
      mitochondrial energy production. The data indicate that the major metabolic roles
      of PC in invasive breast cancer are primarily anaplerosis, pyruvate cycling and
      mitochondrial biosynthesis of precursors of cellular components required for
      breast cancer cell growth and replication.

PMID- 27890530
TI  - Provider Perspectives on Adding Biomarker Screening for Tobacco Smoke Exposure to
      Lead Screening at Well-Child Visits.
AB  - INTRODUCTION: Measurement of cotinine, a biomarker of tobacco smoke exposure, can
      accurately identify children at risk of health consequences from secondhand
      smoke. This study reports perspectives from pediatric health care providers on
      incorporating routine cotinine screening into well-child visits. METHODS: Key
      informant interviews (N = 28) were conducted with pediatric primary care
      providers: physicians, nurse practitioners, and registered nurses. RESULTS:
      Themes identified in the interviews included the following: (a) Cotinine
      screening would assess children's exposure to tobacco smoke more reliably than
      parental report; (b) Addressing positive cotinine screening results might require
      additional resources; (c) Wheezing and a history of emergency department visits
      increased the salience of cotinine screening; and (d) A better understanding of
      the significance of specific cotinine test values would improve utility.
      DISCUSSION: Pediatric providers see advantages of biomarker screening for tobacco
      smoke exposure at well-child visits, especially for children with wheezing, but
      have concerns about limited capacity for follow-up with parents.

PMID- 27890531
TI  - Short-term effects of diabetes on neurosteroidogenesis in the rat hippocampus.
AB  - Diabetes may induce neurophysiological and structural changes in the central
      nervous system (i.e., diabetic encephalopathy). We here explored whether the
      levels of neuroactive steroids (i.e., neuroprotective agents) in the hippocampus
      may be altered by short-term diabetes (i.e., one month). To this aim, by liquid
      chromatography-tandem mass spectrometry we observed that in the experimental
      model of the rat raised diabetic by streptozotocin injection, one month of
      pathology induced changes in the levels of several neuroactive steroids, such as
      pregnenolone, progesterone and its metabolites (i.e., tetrahydroprogesterone and
      isopregnanolone) and testosterone and its metabolites (i.e., dihydrotestosterone
      and 3alpha-diol). Interestingly these brain changes were not fully reflected by
      the plasma level changes, suggesting that early phase of diabetes directly
      affects steroidogenesis and/or steroid metabolism in the hippocampus. These
      concepts are also supported by the findings that crucial steps of steroidogenic
      machinery, such as the gene expression of steroidogenic acute regulatory protein
      (i.e., molecule involved in the translocation of cholesterol into mitochondria)
      and cytochrome P450 side chain cleavage (i.e., enzyme converting cholesterol into
      pregnenolone) and 5alpha-reductase (enzyme converting progesterone and
      testosterone into their metabolites) are also affected in the hippocampus. In
      addition, cholesterol homeostasis as well as the functionality of mitochondria, a
      key organelle in which the limiting step of neuroactive steroid synthesis takes
      place, are also affected. Data obtained indicate that short-term diabetes alters
      hippocampal steroidogenic machinery and that these changes are associated with
      impaired cholesterol homeostasis and mitochondrial dysfunction in the
      hippocampus, suggesting them as relevant factors for the development of diabetic
      encephalopathy.

PMID- 27890532
TI  - What governs successful performance of a complex whole body movement: The Kovacs
      release-regrasp on horizontal bar?
AB  - The Kovacs is a release and regrasp skill performed on the horizontal bar in
      men's artistic gymnastics. It is a popular skill in elite competitive gymnastics
      with over 40% of male gymnasts performing a variation of the Kovacs at the London
      2012 Olympics. In the qualifying competition 84% of Kovacs were successfully
      regrasped, with the remaining 16% resulting in a fall. The aim of the present
      study was to determine why some gymnasts are more successful than others at
      regrasping the bar, with a secondary aim to determine how a less successful
      gymnast could alter his technique in order to become more successful. Nine
      performances of the Kovacs by each of two gymnasts, one 100% successful and one
      11% successful, were analysed to determine differences in release and regrasp
      parameters. The technique of the less successful gymnast was optimised using a
      computer simulation model to increase the percentage of catches (success rate).
      The successful gymnast had larger and more consistent release windows and a
      radial velocity towards the bar at regrasp. The less successful gymnast had
      higher horizontal velocity at release and a mean radial velocity away from the
      bar at regrasp. Optimising his simulated technique increased the rate of success
      from 11% to 93%. The actions prior to release were performed earlier than in the
      recorded performances leading to a more vertical path of the mass centre at
      release and a radial velocity towards the bar at regrasp.

PMID- 27890533
TI  - Full-thickness tears of the supraspinatus tendon: A three-dimensional finite
      element analysis.
AB  - Knowledge regarding the likelihood of propagation of supraspinatus tears is
      important to allow an early identification of patients for whom a conservative
      treatment is more likely to fail, and consequently, to improve their clinical
      outcome. The aim of this study was to investigate the potential for propagation
      of posterior, central, and anterior full-thickness tears of different sizes using
      the finite element method. A three-dimensional finite element model of the
      supraspinatus tendon was generated from the Visible Human Project data. The
      mechanical behaviour of the tendon was fitted from experimental data using a
      transversely isotropic hyperelastic constitutive model. The full-thickness tears
      were simulated at the supraspinatus tendon insertion by decreasing the interface
      area. Tear sizes from 10% to 90%, in 10% increments, of the anteroposterior
      length of the supraspinatus footprint were considered in the posterior, central,
      and anterior regions of the tendon. For each tear, three finite element analyses
      were performed for a supraspinatus force of 100N, 200N, and 400N. Considering a
      correlation between tendon strain and the risk of tear propagation, the simulated
      tears were compared qualitatively and quantitatively by evaluating the volume of
      tendon for which a maximum strain criterion was not satisfied. The finite element
      analyses showed a significant impact of tear size and location not only on the
      magnitude, but also on the patterns of the maximum principal strains. The
      mechanical outcome of the anterior full-thickness tears was consistently, and
      significantly, more severe than that of the central or posterior full-thickness
      tears, which suggests that the anterior tears are at greater risk of propagating
      than the central or posterior tears.

PMID- 27890534
TI  - Effects of arterial wall models and measurement uncertainties on cardiovascular
      model predictions.
AB  - We developed a methodology to assess and compare the prediction quality of
      cardiovascular models for patient-specific simulations calibrated with
      uncertainty-hampered measurements. The methodology was applied in a one
      dimensional blood flow model to estimate the impact of measurement uncertainty in
      wall model parameters on the predictions of pressure and flow in an arterial
      network. We assessed the prediction quality of three wall models that have been
      widely used in one-dimensional blood flow simulations. A 37-artery network,
      previously used in one experimental and several simulation studies, was adapted
      to patient-specific conditions with a set of three clinically measurable inputs:
      carotid-femoral wave speed, mean arterial pressure and area in the brachial
      artery. We quantified the uncertainty of the predicted pressure and flow waves in
      eight locations in the network and assessed the sensitivity of the model
      prediction with respect to the measurements of wave speed, pressure and cross
      sectional area. Furthermore, we developed novel time-averaged sensitivity indices
      to assess the contribution of model parameters to the uncertainty of time-varying
      quantities (e.g., pressure and flow). The results from our patient-specific
      network model demonstrated that our novel indices allowed for a more accurate
      sensitivity analysis of time-varying quantities compared to conventional Sobol
      sensitivity indices.

PMID- 27890535
TI  - Partial hepatectomy hemodynamics changes: Experimental data explained by closed
      loop lumped modeling.
AB  - The liver function may be degraded after partial liver ablation surgery. Adverse
      liver hemodynamics have been shown to be associated to liver failure. The link
      between these hemodynamics changes and ablation size is however poorly
      understood. This article proposes to explain with a closed-loop lumped model the
      hemodynamics changes observed during twelve surgeries in pigs. The portal venous
      tree is modeled with a pressure-dependent variable resistor. The variables
      measured, before liver ablation, are used to tune the model parameters. Then, the
      liver partial ablation is simulated with the model and the simulated pressures
      and flows are compared with post-operative measurements. Fluid infusion and blood
      losses occur during the surgery. The closed-loop model presented accounts for
      these blood volume changes. Moreover, the impact of blood volume changes and the
      liver lobe mass estimations on the simulated variables is studied. The typical
      increase of portal pressure, increase of liver pressure loss, slight decrease of
      portal flow and major decrease in arterial flow are quantitatively captured by
      the model for a 75% hepatectomy. It appears that the 75% decrease in hepatic
      arterial flow can be explained by the resistance increase induced by the surgery,
      and that no hepatic arterial buffer response (HABR) mechanism is needed to
      account for this change. The different post-operative states, observed in
      experiments, are reproduced with the proposed model. Thus, an explanation for
      inter-subjects post-operative variability is proposed. The presented framework
      can easily be adapted to other species circulations and to different pathologies
      for clinical hepatic applications.

PMID- 27890536
TI  - Estimation of the center of rotation using wearable magneto-inertial sensors.
AB  - Determining the center of rotation (CoR) of joints is fundamental to the field of
      human movement analysis. CoR can be determined using a magneto-inertial
      measurement unit (MIMU) using a functional approach requiring a calibration
      exercise. We systematically investigated the influence of different experimental
      conditions that can affect precision and accuracy while estimating the CoR, such
      as (a) angular joint velocity, (b) distance between the MIMU and the CoR, (c)
      type of the joint motion implemented, (d) amplitude of the angular range of
      motion, (e) model of the MIMU used for data recording, (f) amplitude of additive
      noise on inertial signals, and (g) amplitude of the errors in the MIMU
      orientation. The evaluation process was articulated at three levels: assessment
      through experiments using a mechanical device, mathematical simulation, and an
      analytical propagation model of the noise. The results reveal that joint angular
      velocity significantly impacted CoR identification, and hence, slow joint
      movement should be avoided. An accurate estimation of the MIMU orientation is
      also fundamental for accurately subtracting the contribution owing to gravity to
      obtain the coordinate acceleration. The unit should be preferably attached close
      to the CoR, but both type and range of motion do not appear to be critical. When
      the proposed methodology is correctly implemented, error in the CoR estimates is
      expected to be <3mm (best estimates=2+/-0.5mm). The findings of the present study
      foster the need to further investigate this methodology for application in human
      subjects.

PMID- 27890537
TI  - Computational Fluid Dynamics modeling of contrast transport in basilar aneurysms
      following flow-altering surgeries.
AB  - In vivo measurement of blood velocity fields and flow descriptors remains
      challenging due to image artifacts and limited resolution of current imaging
      methods; however, in vivo imaging data can be used to inform and validate patient
      specific computational fluid dynamics (CFD) models. Image-based CFD can be
      particularly useful for planning surgical interventions in complicated cases such
      as fusiform aneurysms of the basilar artery, where it is crucial to alter
      pathological hemodynamics while preserving flow to the distal vasculature. In
      this study, patient-specific CFD modeling was conducted for two basilar aneurysm
      patients considered for surgical treatment. In addition to velocity fields,
      transport of contrast agent was simulated for the preoperative and postoperative
      conditions using two approaches. The transport of a virtual contrast passively
      following the flow streamlines was simulated to predict post-surgical flow
      regions prone to thrombus deposition. In addition, the transport of a mixture of
      blood with an iodine-based contrast agent was modeled to compare and verify the
      CFD results with X-ray angiograms. The CFD-predicted patterns of contrast flow
      were qualitatively compared to in vivo X-ray angiograms acquired before and after
      the intervention. The results suggest that the mixture modeling approach,
      accounting for the flow rates and properties of the contrast injection, is in
      better agreement with the X-ray angiography data. The virtual contrast modeling
      assessed the residence time based on flow patterns unaffected by the injection
      procedure, which makes the virtual contrast modeling approach better suited for
      prediction of thrombus deposition, which is not limited to the peri-procedural
      state.

PMID- 27890538
TI  - A model for stretch growth of neurons.
AB  - In the first phase of axon growth, axons sprout from neuron bodies and are
      extended by the pull of the migrating growth cones towards their targets.
      Thereafter, once the target is reached, a lesser known second phase of axon
      growth ensues as the mechanical forces from the growth of the animal induce
      extension of the integrated axons in the process of forming tracts and nerves.
      Although there are several microscopic physics based models of the first phase of
      axon growth, to date, there are no models of the very different second phase.
      Here we propose a mathematical model for stretch growth of axon tracts in which
      the rate of production of proteins required for growth is dependent on the
      membrane tension. We assume that growth occurs all along the axon, and are able
      to predict the increase in axon cross-sectional area after they are rapidly
      stretched and held at a constant length for several hours. We show that there is
      a length dependent maximum stretching rate that an axon can sustain without
      disconnection in steady state when the axon length is primarily increased near
      the cell body. Our results could inform better design of stretch growth protocols
      to create transplantable axon tracts to repair the nervous system.

PMID- 27890539
TI  - The potential of individual patient data for research on antidepressant safety
      and efficacy.

PMID- 27890540
TI  - Association of plasma calcium concentrations with alcohol craving: New data on
      potential pathways.
AB  - Recently, calcium was suggested to be the active moiety of acamprosate. We
      examined plasma calcium concentrations in association with severity of alcohol
      dependence and its interaction with regulating pathways and alcohol craving in
      alcohol-dependent patients. 47 inpatient alcohol-dependent patients undergoing
      detoxification treatment underwent laboratory testing, including calcium, sodium,
      liver enzymes as well as serum concentrations of calcitonin, parathyroid hormone
      and vitamin D. The psychometric dimension of craving was analyzed with the
      Obsessive Compulsive Drinking Scale (OCDS). The severity of withdrawal was
      measured with the Alcohol Dependence Scale (ADS) and with the Alcohol Dependence
      Scale for high-risk sample (ADS-HR). The main findings of our investigation are:
      a) a negative correlation of plasma calcium concentrations with alcohol craving
      in different dimensions of the OCDS; b) a negative correlation of plasma calcium
      concentrations with breath alcohol concentration; c) lowered calcitonin
      concentration in the high-risk sample of alcoholics; d) lowered plasma vitamin D
      concentrations in all alcoholic subjects. Our study adds further support for
      lowered plasma calcium concentrations in patients with high alcohol intake and
      especially in patients with increased craving as a risk factor for relapse.
      Lowered calcitonin concentrations in the high-risk sample and lowered vitamin D
      concentrations may mediate these effects. Calcium supplementation could be a
      useful intervention for decreasing craving and relapse in alcohol-dependent
      subjects.

PMID- 27890541
TI  - The expression of plasticity-related genes in an acute model of stress is
      modulated by chronic desipramine in a time-dependent manner within medial
      prefrontal cortex.
AB  - It is well established that stress plays a major role in the pathogenesis of
      neuropsychiatric diseases. Stress-induced alteration of synaptic plasticity has
      been hypothesized to underlie the morphological changes observed by neuroimaging
      in psychiatric patients in key regions such as hippocampus and prefrontal cortex
      (PFC). We have recently shown that a single acute stress exposure produces
      significant short-term alterations of structural plasticity within medial PFC.
      These alterations were partially prevented by previous treatment with chronic
      desipramine (DMI). In the present study we evaluated the effects of acute Foot
      shock (FS)-stress and pre-treatment with the traditional antidepressant DMI on
      the gene expression of key regulators of synaptic plasticity and structure.
      Expression of Homer, Shank, Spinophilin, Densin-180, and the small RhoGTPase
      related gene Rac1 and downstream target genes, Limk1, Cofilin1 and Rock1 were
      investigated 1 day (1d), 7 d and 14d after FS-stress exposure. We found that DMI
      specifically increases the short-term expression of Spinophilin, as well as Homer
      and Shank family genes, and that both acute stress and DMI exert significant long
      term effects on mRNA levels of genes involved in spine plasticity. These findings
      support the knowledge that acute FS stress and antidepressant treatment induce
      both rapid and sustained time-dependent alterations in structural components of
      synaptic plasticity in rodent medial PFC.

PMID- 27890542
TI  - Social Capital and Suicidal Ideation in Community-Dwelling Older Residents: A
      Multilevel Analysis of 10,094 Subjects in Japan.
AB  - OBJECTIVE: Social capital, the collective resources of groups including
      perceptions of trust and reciprocity, is recognized as an important contributor
      to suicide. We examined the association of individual- and community-level social
      capital with suicidal ideation after adjusting for social support among older
      adults living in the community. METHODS: In August 2010 we sent questionnaires to
      all residents aged 65 years and older living in 3 rural municipalities (N =
      21,232) in Okayama Prefecture, Japan; 13,919 questionnaires were returned
      (response rate: 65.6%). The final analysis included 10,094 participants. The
      outcome variable was suicidal ideation. Exposure variables were individual-level
      mistrust and lack of reciprocity (level 1), and the aggregated responses of these
      variables from 35 communities in the municipalities (level 2). Covariates
      included age, sex, educational attainment, marital status, the number of
      cohabitants, years of residence, self-rated socioeconomic status, disability,
      social support, and psychological distress. Multilevel logistic regression
      analysis was performed to obtain odds ratios (ORs) and 95% confidence intervals
      (CIs). RESULTS: After adjusting for social support and psychological distress, we
      found that mistrust and lack of reciprocity were only associated with suicidal
      ideation at the individual level. Stratified analysis showed that among subjects
      with psychological distress, mistrust was associated with suicidal ideation at
      individual (OR: 1.88; 95% CI: 1.42-2.51) and community levels (OR: 1.98; 95% CI:
      1.02-3.81). CONCLUSIONS: Our findings show that individual- and community-level
      social capital is a possible protective factor for suicidal ideation,
      particularly for people with psychological distress.

PMID- 27890544
TI  - Persistent hydrocephalus due to postural activation of a ventricular shunt anti
      gravity device.
AB  - The ever present need to balance over drainage with under drainage in
      hydrocephalus has required innovations including adjustable valves with
      antigravity devices. These are activated in the vertical position to prevent
      siphoning. We describe a group of bedridden patients who presented with
      unexplained under drainage caused by activation of antigravity shunt components
      produced by peculiar head/body position. Retrospective single centre case series
      of hydrocephalus patients, treated with ventriculo-peritoneal (VP) shunt
      insertion between April 2014 - February 2016. These patients presented with
      clinical and radiological under drainage syndrome. Medical notes were reviewed
      for clinical picture and outcome. Radiological studies were reviewed assessing
      shunt placement and ventricular size. Seven patients presented with clinical and
      radiological under drainage syndrome. A consistent posturing of long term hyper
      flexion of the neck whilst lying supine was observed. All patients had similar
      shunt construct (adjustable Miethke ProGAV valve and shunt assistant anti-gravity
      component). In each of those patients a hypothesis was formulated that neck
      flexion was activating the shunt assistance anti-gravity component in supine
      position. Five patients underwent shunt revision surgery removing the shunt
      assistant device from the cranium and adding an anti-gravity component to the
      shunt system at the chest. One had the shunt assistant completely removed and one
      patient was managed conservatively with mobilisation. All patients had clinical
      and radiological improvement. Antigravity shunt components implanted cranially in
      bedridden hydrocephalus patients will produce underdrainage due to head flexion
      induced anti-gravity device activation. In these patients, anti-gravity devices
      should be placed at the chest. Alternatively, special nursing attention should be
      paid to head-trunk angle.

PMID- 27890543
TI  - Hearing Care Intervention for Persons with Dementia: A Pilot Study.
AB  - OBJECTIVE: Hearing loss is a commonly unmet need among adults with dementia that
      may exacerbate common dementia-related behavioral symptoms. Accessing traditional
      audiology services for hearing loss is a challenge because of high cost and time
      commitment. To improve accessibility and affordability of hearing treatment for
      persons with dementia, there is a need for unique service delivery models. The
      purpose of this study is to test a novel hearing intervention for persons with
      dementia and family caregivers delivered in outpatient settings. METHODS: The
      Memory-HEARS pilot study delivered a 2-hour in-person intervention in an
      outpatient setting. A trained interventionist provided hearing screening,
      communication strategies, and provision of and instruction using a simple over
      the-counter amplification device. Caregivers (N = 20) responded to questionnaires
      related to depression, neuropsychiatric symptoms, and caregiver burden at
      baseline and 1-month postintervention. RESULTS: Overall, caregivers believed the
      intervention was beneficial, and most participants with dementia wore the
      amplification device daily. For the depression and neuropsychiatric outcome
      measures, participants with high symptom burden at baseline showed improvement at
      1-month postintervention. The intervention had no effect on caregiver burden.
      Qualitative responses from caregivers described improved engagement for their
      loved ones, such as laughing more, telling more stories, asking more questions,
      and having more patience. CONCLUSION: The Memory-HEARS intervention is a low
      cost, low-risk, nonpharmacologic approach to addressing hearing loss and
      behavioral symptoms in patients with dementia. Improved communication has the
      potential to reduce symptom burden and improve quality of life.

PMID- 27890545
TI  - Organic acid anions: An effective defensive weapon for plants against aluminum
      toxicity and phosphorus deficiency in acidic soils.
AB  - Aluminum (Al) toxicity and phosphorous (P) deficiency are two major limiting
      factors for plant growth on acidic soils. Thus, the physiological mechanisms for
      Al tolerance and P acquisition have been intensively studied. A commonly observed
      trait is that plants have developed the ability to utilize organic acid anions
      (OAs; mainly malate, citrate and oxalate) to combat Al toxicity and P deficiency.
      OAs secreted by roots into the rhizosphere can externally chelate Al3+ and
      mobilize phosphate (Pi), while OAs synthesized in the cell can internally
      sequester Al3+ into the vacuole and release free Pi for metabolism. Molecular
      mechanisms involved in OA synthesis and transport have been described in detail.
      Ensuing genetic improvement for Al tolerance and P efficiency through increased
      OA exudation and/or synthesis in crops has been achieved by transgenic and marker
      assisted breeding. This review mainly elucidates the crucial roles of OAs in
      plant Al tolerance and P efficiency through summarizing associated physiological
      mechanisms, molecular traits and genetic manipulation of crops.

PMID- 27890546
TI  - Radiological evaluation of sphenozygomatic suture fixation for restoration of
      orbital volume: A retrospective study.
AB  - PURPOSE: Lateral displacement of fracture zygomaticomaxillary complex (ZMC) can
      cause significant increase in orbital volume leading to enophthalmos. The aim of
      this study was to radiologically evaluate the efficacy of sphenozygomatic (SZ)
      suture fixation for restoration of orbital volume after elevation of the
      temporalis in cases of fracture ZMC where the fixation of zygomatic arch (ZA) was
      deemed necessary through latero-posterior approach. MATERIALS & METHODS: 43
      operated cases of fracture ZMC using 4-point fixation were divided into two
      groups. Group I (n = 24) cases had undergone reduction and fixation of SZ suture
      as fourth point of fixation by elevating temporalis muscle using hemicoronal
      approach. Group II (n = 19) cases had undergone reduction and fixation of
      Infraorbital (IO) rim as fourth point of fixation using preseptal
      transconjunctival approach. Both the groups were analyzed separately and compared
      for restoring the increased orbital volume on CT. RESULTS: Difference in the pre
      surgical orbital volume of both the groups was found to be statistically
      insignificant [p = .678]. In group I, the average bony orbital volume
      significantly reduced by 3.6 cc from 25.5 cc to 21.9 cc [p = .000] post
      surgically. In group II, the average bony orbital volume reduced by 1.5 cc from
      25.6 cc to 24.1 cc post-surgically There was a significant difference in the
      reduction of the increased orbital volume among the 2 groups (Group I: 3.6 cc,
      group II: 1.5 cc). The amount of reduction was more and statistically significant
      [p = .000] in the group I than group II. CONCLUSION: SZ suture fixation is
      reliable in reducing fractures ZMC and restoring the increased orbital volume
      where the fixation of zygomatic arch (ZA) was deemed necessary through latero
      posterior approach.

PMID- 27890547
TI  - A Delphi study to develop practical diagnostic guidelines for visual stress
      (pattern-related visual stress).
AB  - PURPOSE: Visual stress (VS) is characterised by symptoms of visual perceptual
      distortions and eyestrain when viewing text, symptoms that are alleviated by
      individually prescribed coloured filters. A recent review supports the existence
      of VS and its treatment, but noted that controversy remains, in part due to
      inconsistencies in the diagnosis of the condition. The present paper reviews the
      diagnostic criteria for VS in the literature and reports a Delphi analysis of the
      criteria currently used in clinical practice. METHODS: Twenty-six eyecare
      practitioners were invited to participate in a Delphi study. They were selected
      because they were frequent prescribers of precision tinted lenses. In the first
      round they were sent a list of the indicators for which there is literature to
      suggest a relevance in the diagnosis of VS. The practitioners were invited to
      rank the indicators and add any additional criteria they use in diagnosis. In the
      second round a revised list was circulated, including items added from the
      responses in the first round. RESULTS: The respondents included optometrists,
      orthoptists and opticians. In the first round the response rate was 85%. Ninety
      one percent of those who participated in the first round also responded in the
      second round. Strong indicators in the second round included the symptom of words
      moving when reading, voluntary use of an overlay for a prolonged period, improved
      performance of >=15% with an overlay on the Wilkins Rate of Reading test, and an
      abnormally high score on the Pattern Glare Test. CONCLUSIONS: The strongest
      diagnostic criteria are combined in a diagnostic tool. This is proposed as a
      guide for clinical practice and further research.

PMID- 27890548
TI  - Use of glucose-lowering drugs and risk of fracture in patients with type 2
      diabetes.
AB  - BACKGROUND: Diabetes mellitus is associated with an increased risk of hip
      fracture. The aim of this cohort study was to investigate whether glucose
      lowering drugs influence the risk of hip fracture in patients with incident
      diabetes. METHODS: A study was performed on a cohort of patients with incident
      type 2 diabetes. Diabetes diagnosis was defined using information from the Danish
      National Patient Registry and reimbursement information of glucose-lowering drugs
      from the Register of Medicinal Product Statistics. The period of observation was
      from 01.01.1996 till 31.12.2011. The primary exposure was glucose-lowering drugs
      and the primary endpoint was hip fracture. Unadjusted, adjusted, and propensity
      score adjusted Cox regressions were performed. RESULTS: 5244 patients with type 2
      diabetes with a mean follow up of 5.5years were included in the study. Use of
      sulphonylureas within the last 90days was associated with hip fracture in
      patients with type 2 diabetes, hazard ratio 1.64 (95% confidence interval:
      1.54,1.75), whereas ever use of sulohonylyreas was not associated with an
      increased risk of fractures. Use of sulphonylureas within the last 90days was
      also associated with an increased risk of fractures at other sites. Use of
      glitazones within the last 90days was associated with an increased risk of hip
      fracture, hazard ratio 2.07 (95% confidence interval: 1.39,3.07), whereas ever
      use was not associated with an increased risk. CONCLUSIONS: Current use of
      sulphonylureas was associated with hip fracture in patients with type 2 diabetes.
      Speculatively, this may be due to hypoglycemia resulting in falls.

PMID- 27890550
TI  - Paradoxical sleep deprivation in rats causes a selective reduction in the
      expression of type-2 metabotropic glutamate receptors in the hippocampus.
AB  - Paradoxical sleep deprivation in rats is considered as an experimental animal
      model of mania endowed with face, construct, and pharmacological validity. We
      induced paradoxical sleep deprivation by placing rats onto a small platform
      surrounded by water. This procedure caused the animal to fall in the water at the
      onset of REM phase of sleep. Control rats were either placed onto a larger
      platform (which allowed them to sleep) or maintained in their home cage. Sleep
      deprived rats showed a substantial reduction in type-2 metabotropic glutamate
      (mGlu2) receptors mRNA and protein levels in the hippocampus, but not in the
      prefrontal cortex or corpus striatum, as compared to both groups of control rats.
      No changes in the expression of mGlu3 receptor mRNA levels or mGlu1alpha and
      mGlu5 receptor protein levels were found with exception of an increase in
      mGlu1alpha receptor levels in the striatum of SD rats. Moving from these findings
      we treated SD and control rats with the selective mGlu2 receptor enhancer, BINA
      (30mg/kg, i.p.). SD rats were also treated with sodium valproate (300mg/kg, i.p.)
      as an active comparator. Both BINA and sodium valproate were effective in
      reversing the manic-like phenotype evaluated in an open field arena in SD rats.
      BINA treatment had no effect on motor activity in control rats, suggesting that
      our findings were not biased by a non-specific motor-lowering activity of BINA.
      These findings suggest that changes in the expression of mGlu2 receptors may be
      associated with the enhanced motor activity observed with mania.

PMID- 27890549
TI  - Novel functions of circulating Klotho.
AB  - A significant portion of the key biological functions of alphaKlotho (alphaKL)
      and its cognate ligand Fibroblast growth factor-23 (FGF23) have been revealed
      through the study of rare diseases of mineral metabolism. These findings have far
      reaching implications for common disorders such as chronic kidney disease-mineral
      bone disorder (CKD-MBD). alphaKL's predominant effect on mineral homeostasis is
      through its actions in the kidney as a co-receptor for FGF23, however emerging
      data has shed light on its capacity to act as a circulating factor through the
      cleavage of the transmembrane form of alphaKL ('mKL') to produce 'cleaved KL' or
      'cKL'. This review summarizes new findings from studies using extended delivery
      of cKL to mouse models with phenotypes reflecting those arising in CKD-MBD.

PMID- 27890551
TI  - Dual function of OCT2 and MATE1 in cisplatin induced nephrotoxicity.

PMID- 27890552
TI  - Combined Use of Intra-aortic Balloon Pump and Venoarterial Extracorporeal
      Membrane Oxygenation Support With Femoral Arterial Cannulation Impairs Cerebral
      Microcirculation: Evaluation With Laser Speckle Flowgraphy.

PMID- 27890553
TI  - Now You See Me, Now You Don't.

PMID- 27890554
TI  - Endocarditis after interventional repair of the mitral valve: Review of a
      dilemma.
AB  - BACKGROUND: The MitraClip procedure can be an alternative treatment option for
      patients with high surgical risk for whom surgical treatment is contraindicated.
      Patients with prosthetic material have an increased risk for infective
      endocarditis. HYPOTHESIS: Incidence, treatment and outcome of patients with
      endocarditis after interventional mitral valve repair are not known. METHODS: We
      searched for articles using PubMed using the terms "interventional mitral valve
      repair", "mitraclip" and "endocarditis". We have also searched for case reports
      in major congresses. Furthermore, we report two cases. RESULTS: Four cases of IE
      after MitraClip were found in addition to our cases. The leading cause is a
      bacterial infection, typically with staphylococcal bacteria. Approximately two
      thirds of these patients underwent surgery. Short-term outcome seems to be
      reasonable for these patients. During the early postoperative period and if
      Staphylococcus aureus can be cultivated mortality seems to be significantly
      elevated. CONCLUSION: IE after MitraClip procedure is a dilemma. While surgical
      bail-out seems to be the favorable treatment option, patients were rejected
      conventional surgery in first place due to their high operative risk. Best
      treatment recommendation must be made on an individual basis. Predisposing
      factors should be conscientiously addressed prior to the procedure.

PMID- 27890555
TI  - Response to commentaries on The American Academy of Pediatrics Workforce Survey
      for the Section on Urology 2015.

PMID- 27890556
TI  - Commentary to "The American Academy of Pediatrics Workforce Survey for the
      Section on Urology 2015".

PMID- 27890557
TI  - Anaphylaxis in a health maintenance organization: International Classification of
      Diseases coding and epinephrine auto-injector prescribing.
AB  - BACKGROUND: Accurate estimates of the incidence of anaphylaxis are limited.
      Current International Classification of Diseases, Ninth Revision (ICD-9) codes
      complicate accurate diagnosis of anaphylaxis and assessment of appropriate
      epinephrine prescribing. OBJECTIVE: To quantify the incidence and demographic
      character of patients with anaphylaxis-related ICD-9 codes in a large health
      maintenance organization and analyze epinephrine prescribing and dispensing
      rates. METHODS: All patients included had at least 12 months of continuous
      membership over a 4-year period from January 1, 2008 to December 31, 2012 and
      were selected based on anaphylaxis-related ICD-9 codes (N = 159,172). This
      algorithm was extrapolated from a previous study that used expanded ICD-9 codes
      to identify more cases of anaphylaxis. Individual chart reviews found that many
      expanded ICD-9 codes represented unconfirmed cases of anaphylaxis and therefore
      were excluded, resulting in analysis of 52,405 patients. RESULTS: Incidence of
      anaphylaxis over 4 years was 2.07%, with female predominance (56.5%) over male
      predominance (43.5%). Epinephrine was prescribed in 16.2% of total cases. Highest
      rates of epinephrine prescription were for traditional ICD-9 codes 995.0 (other
      anaphylactic shock) and 995.60 to 995.69 (anaphylactic shock caused by food) at
      49.3% and 58.6%, respectively. Of the cases in which an epinephrine auto-injector
      was prescribed, it was dispensed 95.9% of the time, independent of copayment
      amount. CONCLUSION: Low epinephrine auto-injector prescribing rates in cases of
      anaphylaxis suggest the continued difficulty in the diagnosis of anaphylaxis and
      could result in suboptimal treatment of potential future episodes.

PMID- 27890558
TI  - ASK1 regulates the survival of neuroblastoma cells by interacting with TLX and
      stabilizing HIF-1alpha.
AB  - Elevated expression of TLX (also called as NR2E1) in neuroblastoma (NB)
      correlates with unfavorable prognosis, and TLX is required for self-renewal of NB
      cells. Knockdown of TLX has been shown to reduce the NB sphere-forming ability.
      ASK1 (MAP3K5) and TLX expression are both enhanced in SP (side population) NB and
      patient-derived primary NB sphere cell lines, but the majority of non-SP NB lines
      express lower ASK1 expression. We found that ASK1 phosphorylated and stabilized
      TLX, which led induction of HIF-1alpha, and its downstream VEGF-A in an Akt
      dependent manner. In depleting ASK1 upon hypoxia, TLX decreased and the apoptosis
      ratio of NB cells was enhanced, while low-ASK1-expressing NB cell lines were
      refractory in TUNEL assay by using flow cytometry. Interestingly, primary NB
      spheres cell lines express only high levels of active pASK1Thr-838 but the
      established cell lines expressed inhibitory pASK1Ser-966, and both could be
      targeted by ASK1 depletion. We report a novel pro-survival role of ASK1 in the
      tumorigenic NB cell populations, which may be applied as a therapeutic target,
      inducing apoptosis specifically in cancer stem cells.

PMID- 27890559
TI  - Fluoxetine and its active metabolite norfluoxetine disrupt estrogen synthesis in
      a co-culture model of the feto-placental unit.
AB  - The effects of fluoxetine, one of the most prescribed selective serotonin
      reuptake inhibitors (SSRIs) during pregnancy, and its active metabolite
      norfluoxetine were studied on placental aromatase (CYP19) and feto-placental
      steroidogenesis. Fluoxetine did not alter estrogen secretion in co-culture of
      fetal-like adrenocortical (H295R) and trophoblast-like (BeWo) cells used as a
      model of the feto-placental unit, although it induced CYP19 activity, apparently
      mediated by the serotonin (5-HT)2A receptor/PKC signaling pathway. Norfluoxetine
      decreased estrogen secretion in the feto-placental co-culture and competitively
      inhibited catalytic CYP19 activity in BeWo cells. Decreased serotonin transporter
      (SERT) activity in the co-culture was comparable to 17beta-estradiol treatment of
      BeWo cells. This work shows that the complex interaction of fluoxetine and
      norfluoxetine with placental estrogen production, involves 5-HT-dependent and 
      independent mechanisms. Considering the crucial role of estrogens during
      pregnancy, our results raise concern about the impact of SSRI treatment on
      placental function and fetal health.

PMID- 27890560
TI  - The hippocampal transcriptomic signature of stress resilience in mice with
      microglial fractalkine receptor (CX3CR1) deficiency.
AB  - Clinical studies suggest that key genetic factors involved in stress resilience
      are related to the innate immune system. In the brain, this system includes
      microglia cells, which play a major role in stress responsiveness. Consistently,
      mice with deletion of the CX3CR1 gene (CX3CR1-/- mice), which in the brain is
      expressed exclusively by microglia, exhibit resilience to chronic stress. Here,
      we compared the emotional, cognitive, neurogenic and microglial responses to
      chronic unpredictable stress (CUS) between CX3CR1-/- and wild type (WT) mice.
      This was followed by hippocampal whole transcriptome (RNA-seq) analysis. We found
      that following CUS exposure, WT mice displayed reduced sucrose preference,
      impaired novel object recognition memory, and reduced neurogenesis, whereas
      CX3CR1-/- mice were completely resistant to these effects of CUS. CX3CR1-/- mice
      were also resilient to the memory-suppressive effect of a short period of
      unpredictable stress. Microglial somas were larger in CX3CR1-/- than in WT, but
      in both genotypes CUS induced a similar decline in hippocampal microglial density
      and processes length. RNA sequencing and pathway analysis revealed basal strain
      differences, particularly reduced expression of interferon (IFN)-regulated and
      MHC class I gene transcripts in CX3CR1-/- mice. Furthermore, while CUS exposure
      similarly altered neuronal gene transcripts (e.g. Arc, Npas4) in both strains,
      transcripts downstream of hippocampal estrogen receptor signaling (particularly
      Igf2 and Igfbp2) were altered only in CX3CR1-/- mice. These findings indicate
      that emotional and cognitive stress resilience involves CX3CR1-dependent basal
      and stress-induced alterations in hippocampal transcription, implicating
      inhibition of CX3CR1 signaling as a novel approach for promoting stress
      resilience.

PMID- 27890561
TI  - Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall.
AB  - INTRODUCTION: The present study investigated the effect of adjuvant chemotherapy
      and radiation on survival among patients undergoing chest wall resection for T3N0
      non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with T3N0
      NSCLC who underwent chest wall resection were identified in the National Cancer
      Data Base in 2004 to 2012. The cohort was divided into patients who had received
      adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant
      treatment. Kaplan-Meier and log-rank tests were used to compare overall survival,
      and a bootstrapped Cox proportional hazards model was used to determine the
      significant contributors to survival. A subset analysis was performed with
      stratification by margin status and tumor size. RESULTS: Of 759 patients
      identified, 42.0% underwent surgery alone, 23.3% underwent surgery followed by
      chemotherapy, 22.3% underwent surgery followed by chemoradiation therapy, and
      12.3% underwent surgery followed by radiotherapy alone. Tumors > 4 cm benefited
      from adjuvant chemotherapy and radiation therapy in the multivariable analysis,
      and those <= 4 cm benefited only from adjuvant chemotherapy. The subgroup
      analysis by margin status identified that margin-positive patients with tumors >
      4 cm benefited significantly from either adjuvant chemoradiation therapy or
      radiation therapy alone. CONCLUSION: T3N0 NSCLC with chest wall invasion requires
      unique management compared with other stage IIB tumors. An important determinant
      of management is tumor size, with tumors <= 4 cm benefiting from adjuvant
      chemotherapy and tumors > 4 cm benefiting from adjuvant chemotherapy if margin
      negative and adjuvant chemoradiation therapy or radiotherapy if margin positive.

PMID- 27890562
TI  - Tailor-made fibroblast-specific and antibiotic-free interleukin 12 plasmid for
      gene electrotransfer-mediated cancer immunotherapy.
AB  - Electrotransfer mediated delivery of interleukin-12 (IL-12) gene, encoded on a
      plasmid vector, has already been demonstrated to have a potent antitumor efficacy
      and great potential for clinical application. In the present study, our aim was
      to construct an optimized IL-12-encoding plasmid that is safe from the regulatory
      point of view. In light of previous studies demonstrating that IL-12 should be
      released in a tumor localized manner for optimal efficacy, the strong ubiquitous
      promoter was replaced with a weak endogenous promoter of the collagen 2 gene,
      which is specific for fibroblasts. Next, to comply with increasing regulatory
      demands for clinically used plasmids, the expression cassette was cloned in a
      plasmid lacking the antibiotic resistance gene. The constructed fibroblast
      specific and antibiotic-free IL-12 plasmid was demonstrated to support low IL-12
      expression after gene electrotransfer in selected cell lines. Furthermore, the
      removal of antibiotic resistance did not affect the plasmid expression profile
      and lowered its cytotoxicity. With optimal IL-12 expression and minimal transgene
      non-specific effects, i.e., low cytotoxicity, the constructed plasmid could be
      especially valuable for different modern immunological approaches to achieve
      localized boosting of the host's immune system.

PMID- 27890563
TI  - Exposure factors for cleaning, automotive care, and surface protection products
      for exposure assessments.
AB  - Accurately measuring the usage patterns of consumer products (CPs) is important
      to conduct realistic exposure assessments. We determined the exposure factors for
      18 consumer products: household bleach, mold stain remover, all-purpose cleaner,
      washing machine cleaner, air conditioner cleaner, glass cleaner, drain cleaner,
      adhesive remover, liquid snow chain, tire shine spray, wheel cleaner, rain
      repellent, car wax spray, leather polish, furniture polish, anti-fog product,
      fabric waterproofing spray, and rust inhibitor. Field survey staff visited homes
      and collected product use information via face-to-face interviews. In total,
      10,000 participants (5010 men and 4990 women) aged 15 years and older completed
      the questionnaire. Household bleach had the highest use rate of 47.4% and use
      rates for the other products ranged from 0.8 to 21.7%. The use rates of many CPs
      differed by age group and gender. Many household cleaning products were used
      regularly, but some products, such as air conditioner cleaner and liquid snow
      chain, were used in specific seasons or for specific purposes; therefore, they
      were used less frequently compared to cleaning products. These exposure factor
      data will be useful as input data for exposure and risk assessments and setting
      safety guidelines.

PMID- 27890564
TI  - Phytochemical and phytopharmacological review of Perilla frutescens L.
      (Labiatae), a traditional edible-medicinal herb in China.
AB  - Perilla frutescens (L.) Britt., a worldwide distributed plant, is an important
      economic crop and with a long cultivation history in China as well as some other
      countries in Asia. Except for the edible applications, the plant of P. frutescens
      is also traditionally used as a medicinal herb in China for thousands years. The
      leaves, seeds and stems of P. frutescens are recommended by the Chinese
      Pharmacopeia as three medicinal materials for various therapeutic applications.
      In the past decades, amount investigations have been done about different aspects
      for P. frutescens. However, no literature review about these works has been
      compiled. This review aims to present the findings of research conducted up-to
      date (2015) on the traditional use, phytochemicals, pharmacological activities
      and toxicities of P. frutescens to provide scientific evidence for well
      understanding and future research of P. frutescens. It was found that more than
      100 compounds have been reported for P. frutescens and most of them are
      contributed to its medical benefits such as anti-allergic, anti-inflammatory,
      anti-oxidant, anticancer, anti-microbial, anti-depressive and anti-cough effects.
      Toxicology studies have been conducted to evaluate the safety of P. frutescens to
      provide information on their dosages and usages.

PMID- 27890565
TI  - Three-generation reproduction toxicity study of genetically modified rice with
      insect resistant genes.
AB  - In the present work, we evaluated the three generation reproductive toxicity of
      the genetically modified rice with insectresistant cry1Ac and sck genes. 120
      Sprague-Dawley (SD) rats were divided into three groups which were fed with
      genetically modified rice diet (GM group), parental control rice diet (PR group)
      and AIN-93 control diet (both used as negative control) respectively. Bodyweight,
      food consumption, reproductive data, hematological parameters, serum chemistry,
      relative organ weights and histopathology for each generation were examined
      respectively. All the hematology and serum chemistry parameters, organ/body
      weight indicators were within the normal range or no change to the adverse
      direction was observed, although several differences in hematology and serum
      chemistry parameters (WBC, BUN, LDH of male rat, PLT, PCT, MPV of female rats),
      reproductive data (rate of morphologically abnormal sperm) were observed between
      GM rice group and two control groups. No macroscopic or histological adverse
      effects were found or considered as treatment-related, either. Overall, the three
      generation study of genetically modified rice with cry1Ac and sck genes at a high
      level showed no unintended adverse effects on rats's reproductive system.

PMID- 27890566
TI  - Management of interruptions to fractionated radiotherapy treatments: Four and a
      half years of experience.
AB  - BACKGROUND AND PURPOSE: The study objective was to report our four-and-a half
      years experience (March 1 2011-August 15 2015) of a program to manage
      interruptions in fractionated radiotherapy treatments. METHODS: A program was
      developed, based on a specific database, to manage treatment interruptions.
      Benefits of the program were analyzed in reference to previously published data.
      Analysis was also performed of two measures to reduce OTT prolongation and
      improve treatment outcomes: working on public holidays and conducting treatment
      unit maintenance on Saturdays. RESULTS: The study included 2352 patients.
      Patients with head and neck cancer obtained the greatest benefit from the
      program, with a mean increase in TCP of 3.5% and a benefit of at least 4% in
      45.6% of them. In prostate cancer patients, the likelihood of biochemical failure
      was reduced by a mean of 2.0% and was reduced by at least 4% in 19.7% of them.
      Application of the two proposed measures would have improved the TCP by a mean of
      5.4% in head and neck cancer patients. The impact of the compensations program
      and proposed measures is lesser in the remaining cancer types studied.
      CONCLUSIONS: Implementation of a compensation program has a significant impact on
      patients with head and neck or prostate cancer but OTT prolongation remains
      excessive in many treatments. The introduction of fractions on public holidays
      would assist in the meeting of recommendations for these patients.

PMID- 27890567
TI  - Commissioning of the 4-D treatment delivery system for organ motion management in
      synchrotron-based scanning ion beams.
AB  - PURPOSE: The aim of this work was the commissioning of delivery procedures for
      the treatment of moving targets in scanning pencil beam hadrontherapy. METHODS:
      EBT3 films fixed to the Anzai Respiratory Phantom were exposed to carbon ion
      scanned homogeneous fields (E=332MeV/u). To evaluate the interplay effect, field
      size and flatness for 3 different scenarios were compared to static condition:
      gated irradiation or repainting alone and combination of both. Respiratory signal
      was provided by Anzai pressure sensor or optical tracking system (OTS). End
      exhale phase and 1s gating window were chosen (2.5mm residual motion). Dose
      measurements were performed using a PinPoint ionization chamber inserted into the
      Brainlab ET Gating Phantom. A sub-set of tests was also performed using proton
      beams. RESULTS: The combination of gating technique and repainting (N=5) showed
      excellent results (6.1% vs 4.3% flatness, identical field size and dose deviation
      within 1.3%). Treatment delivery time was acceptable. Dose homogeneity for gated
      irradiation alone was poor. Both Anzai sensor and OTS appeared suitable for
      providing respiratory signal. Comparisons between protons and carbon ions showed
      that larger beam spot sizes represent more favorable condition for minimizing
      motion effect. CONCLUSION: Results of measurements performed on different
      phantoms showed that the combination of gating and layered repainting is suitable
      to treat moving targets using scanning ion beams. Abdominal compression using
      thermoplastic masks, together with multi-field planning approach and multi
      fractionation, have also been assessed as additional strategies to mitigate the
      effect of patient respiration in the clinical practice.

PMID- 27890568
TI  - Dose calculation algorithm accuracy for small fields in non-homogeneous media:
      The lung SBRT case.
AB  - This review addresses the theme of dose calculation accuracy in the case of the
      stereotactic treatment of lung lesions. Based on the classical categories of type
      "a", "b" and "c" algorithms (according to their degree of complexity in the
      management of charged particle transport), a summary of findings from literature
      is reported. Two main critical areas have been identified: the use of small
      fields and the presence of low density medium. Concerning the latter point, the
      algorithm accuracy is intrinsic of the algorithm core, and, notwithstanding the
      materials discretization and their chemical composition knowledge, type "c" are,
      at the most, able to reproduce the actual physical dose distribution in
      heterogeneous media. For what concerns the small field management, the final
      accuracy could be strongly related to the beam configuration appropriateness in
      the TPS (as well for MC this relates to the proper linac head description). As a
      very crude summary, type "a" should be considered as unsuitable for this kind of
      treatment calculations (with differences of the order of 20-30%), while type "b"
      and "c" could keep their accuracy approximatively within 10 and 5%, respectively.

PMID- 27890569
TI  - Multi-strip silicon sensors for beam array monitoring in micro-beam radiation
      therapy.
AB  - We present here the latest results from tests performed at the ESRF ID17 and ID21
      beamlines for the characterization of novel beam monitors for Microbeam Radiation
      Therapy (MRT), which is currently being implemented at ID17. MRT aims at treating
      solid tumors by exploiting an array of evenly spaced microbeams, having an energy
      spectrum distributed between 27 and 600keV and peaking at 100keV. Given the high
      instantaneous dose delivered (up to 20kGy/s), the position and the intensity of
      the microbeams has to be precisely and instantly monitored. For this purpose, we
      developed dedicated silicon microstrip beam monitors. We have successfully
      characterized them, both with a microbeam array at ID17, and a submicron scanning
      beam at ID21. We present here the latest results obtained in recent tests along
      with an outlook on future developments.

PMID- 27890570
TI  - The spectrum of CYP21A2 mutations in Congenital Adrenal Hyperplasia in an Indian
      cohort.
AB  - Congenital Adrenal Hyperplasia (CAH) is a common autosomal recessive disorder of
      the adrenal steroidogenic pathway. The most common form of CAH is due to
      mutations in CYP21A2 gene. The incidence of mutations in the CYP21A2 gene and the
      genotype-phenotype correlations vary among different populations. Therefore, the
      aim of the study was to establish the spectrum of mutations and to evaluate
      genotype-phenotype correlation in Indian CAH population. Molecular defects were
      investigated in 110 alleles (55 patients) in the present study. Notably, we
      identified disease causing mutations in 106 of 110 (96.4%) alleles whereas the
      frequency of undetectable mutations was 3.6%. The i2g mutation (20%) was found to
      be the most common in CAH patients. The second most common mutation was p.R356W
      (14.5%). p.I172N and 8-bp deletion in exon 3 accounted for 12.7% of the mutated
      alleles. In descending order, the other mutations present were p.Q318X (9%), E6
      Cluster (5.4%), p.V281L (3.6%) and large gene deletion (3.6%). Additionally,
      p.P267L and frameshift mutation (L307fs/F306+T) were also detected in the Indian
      cohort with frequency of 1.8% and 5.4% respectively.rare mutation/rare mutations
      in the CYP21A2 gene were detected viz., p.D234D (NCBI accession number -
      KF812549), p.F306V (NCBI accession number - KF534754), p.P357P (NCBI accession
      number - KF692099) and p.H365N (NCBI accession number - KF447378). The genotypes
      of the patients were categorized into four groups null, A, B and C. Of note,
      correlation between genotype and phenotype is sufficiently strong, to be of
      clinical significance in the genetic counseling.

PMID- 27890571
TI  - Facile fabrication of poly(acrylic acid) coated chitosan nanoparticles with
      improved stability in biological environments.
AB  - Chitosan is one of the most important and commonly used natural polysaccharides
      in drug delivery for its biocompatible and biodegradable properties. However,
      poor blood circulation of the chitosan nanoparticles due to their cationic nature
      is one of the major bottlenecks of chitosan-based drug delivery systems. To
      address this problem, a versatile platform based on poly(acrylic acid) (PAA)
      coated ionically cross-linked chitosan/tripolyphosphate nanoparticles (CTS/TPP
      PAA NPs), is reported. The zeta potentials of CTS/TPP and CTS/TPP-PAA NPs are
      approximately 33mV and -25mV, respectively. CTS/TPP NPs quickly aggregate in PBS
      (phosphate buffered saline) and DMEM (Dulbecco's modified Eagle's medium).
      Conversely, CTS/TPP-PAA NPs exhibit excellent colloidal stability in plasma
      solution for more than 24h. The PAA coating also endows CTS/TPP-PAA NPs with
      decreased protein adsorption capacity and improved buffering capacity. More
      importantly, the residual carboxyl and amino groups on CTS/TPP-PAA NPs provide
      abundant reactive sites for further functional modifications. Therefore, the
      CTS/TPP-PAA NPs reported here may be useful as an alternative drug delivery
      system.

PMID- 27890572
TI  - Preservative loss from silicone tubing during filling processes.
AB  - Significant loss of preservative was observed during filling of drug products
      during filling line stops. This study evaluated the losses of three commonly used
      preservatives in protein drugs, i.e. benzyl alcohol, phenol, and m-cresol.
      Concentration losses during static incubation were quantified and interpreted
      with regard to the potential driving forces for the underlying sorption,
      diffusion, and desorption steps. Partitioning from the solution into the silicone
      polymer was identified as the most decisive parameter for the extent of
      preservative loss. Additionally, the influence of tubing inner diameter, starting
      concentration as well as silicone tubing type was evaluated. Theoretical
      calculations assuming equilibrium between solution and tubing inner surface and
      one-directional diffusion following Fick's first law were used to approximate
      experimental data. Since significant losses were found already after few minutes,
      adequate measures must be taken to avoid deviations during filling of
      preservative-containing protein solutions that may impact product quality or
      antimicrobial efficacy. As a possible alternative to the highly permeable
      silicone tubing, a specific make of fluoropolymer tubing was identified being
      suitable for peristaltic pumps and not showing any preservative losses.

PMID- 27890573
TI  - Pegylated oleic acid: A promising amphiphilic polymer for nano-antibiotic
      delivery.
AB  - Vancomycin (VM), a last resort to control methicillin-resistant S. aureus (MRSA)
      infections, is on the verge of becoming ineffective. Novel nano delivery systems
      of VM have the potential to combat MRSA. The search for novel materials for
      nanoantibiotic development is therefore an active research area. In this study,
      oleic acid (OA) was coupled with monomethoxy polyethylene glycol (mPEG) to obtain
      a novel bio-safe amphiphilic polymer, mPEG-OA. The critical micelle concentration
      of mPEG-OA, was found to be 4.5*10-8m/L. VM-loaded polymersomes were prepared
      from mPEG-OA and evaluated for size, polydispersity index (PDI), zeta potential
      (ZP), surface morphology, drug release, in vitro and in vivo antibacterial
      activity. The size, PDI and ZP of VM-loaded polymersomes were 142.9+/-7.5nm,
      0.228+/-0.03 and -18.3+/-3.55mV respectively. Transmission electron microscopy
      images revealed the spherical shape of polymersomes. The encapsulation efficiency
      was 53.64+/-1.86%. The drug release from polymersomes was sustained and in vitro
      antibacterial activity was 42- and 5-fold more against S. aureus and MRSA,
      compared with plain VM. An in vivo BALB/c mice, skin infection models revealed
      that treatment with VM-loaded polymersomes significantly reduced the MRSA burden
      compared with plain VM and blank polymersomes. There was a 183 and a 25-fold
      reduction in the MRSA colony finding units load in mice skin treated with VM
      loaded polymersomes compared to that treated with blank polymersomes and bare VM
      respectively. In summary, the developed VM-loaded polymersomes from novel mPEG-OA
      polymer were found to be a promising nanoantibiotic against MRSA.

PMID- 27890574
TI  - Modeling the role of information and limited optimal treatment on disease
      prevalence.
AB  - Disease outbreaks induce behavioural changes in healthy individuals to avoid
      contracting infection. We first propose a compartmental model which accounts for
      the effect of individual's behavioural response due to information of the disease
      prevalence. It is assumed that the information is growing as a function of
      infective population density that saturates at higher density of infective
      population and depends on active educational and social programmes. Model
      analysis has been performed and the global stability of equilibrium points is
      established. Further, choosing the treatment (a pharmaceutical intervention) and
      the effect of information (a non-pharmaceutical intervention) as controls, an
      optimal control problem is formulated to minimize the cost and disease fatality.
      In the cost functional, the nonlinear effect of controls is accounted. Analytical
      characterization of optimal control paths is done with the help of Pontryagin's
      Maximum Principle. Numerical findings suggest that if only control via
      information is used, it is effective and economical for early phase of disease
      spread whereas treatment works well for long term control except for initial
      phase. Furthermore, we observe that the effect of information induced behavioural
      response plays a crucial role in the absence of pharmaceutical control. Moreover,
      comprehensive use of both the control interventions is more effective than any
      single applied control policy and it reduces the number of infective individuals
      and minimizes the economic cost generated from disease burden and applied
      controls. Thus, the combined effect of both the control policies is found more
      economical during the entire epidemic period whereas the implementation of a
      single policy is not found economically viable.

PMID- 27890575
TI  - 3D hybrid modelling of vascular network formation.
AB  - We develop an off-lattice, agent-based model to describe vasculogenesis, the de
      novo formation of blood vessels from endothelial progenitor cells during
      development. The endothelial cells that comprise our vessel network are viewed as
      linearly elastic spheres that move in response to the forces they experience. We
      distinguish two types of endothelial cells: vessel elements are contained within
      the network and tip cells are located at the ends of vessels. Tip cells move in
      response to mechanical forces caused by interactions with neighbouring vessel
      elements and the local tissue environment, chemotactic forces and a persistence
      force which accounts for their tendency to continue moving in the same direction.
      Vessel elements are subject to similar mechanical forces but are insensitive to
      chemotaxis. An angular persistence force representing interactions with the local
      tissue is introduced to stabilise buckling instabilities caused by cell
      proliferation. Only vessel elements proliferate, at rates which depend on their
      degree of stretch: elongated elements have increased rates of proliferation, and
      compressed elements have reduced rates. Following division, the fate of the new
      cell depends on the local mechanical environment: the probability of forming a
      new sprout is increased if the parent vessel is highly compressed and the
      probability of being incorporated into the parent vessel increased if the parent
      is stretched. Simulation results reveal that our hybrid model can reproduce the
      key qualitative features of vasculogenesis. Extensive parameter sensitivity
      analyses show that significant changes in network size and morphology are induced
      by varying the chemotactic sensitivity of tip cells, and the sensitivities of the
      proliferation rate and the sprouting probability to mechanical stretch. Varying
      the chemotactic sensitivity directly influences the directionality of the
      networks. The degree of branching, and thereby the density of the networks, is
      influenced by the sprouting probability. Glyphs that simultaneously depict
      several network properties are introduced to show how these and other network
      quantities change over time and also as model parameters vary. We also show how
      equivalent glyphs constructed from in vivo data could be used to discriminate
      between normal and tumour vasculature and, in the longer term, for model
      validation. We conclude that our biomechanical hybrid model can generate vascular
      networks that are qualitatively similar to those generated from in vitro and in
      vivo experiments.

PMID- 27890576
TI  - Wing geometry of Phlebotomus stantoni and Sergentomyia hodgsoni from different
      geographical locations in Thailand.
AB  - Geographic populations of the two main sandflies genera present in Thailand were
      studied for species and population identification. Size and shape of Phlebotomus
      stantoni and Sergentomyia hodgsoni from different island and mainland locations
      were examined by landmark-based geometric morphometrics. Intraspecific and
      interspecific wing comparison was carried out based on 12 anatomical landmarks.
      The wing centroid size of P. stantoni was generally larger than that of S.
      hodgsoni. Within both species, wings from the continent were significantly larger
      than those from island populations. Size variation could be significant between
      geographic locations, but could also overlap between genera. The wing venation
      geometry showed non-overlapping differences between two species. The within
      species variation of geometric shape between different geographical locations was
      highly significant, but it could not interfere with the interspecies difference.
      The lack of species overlapping in shape, and the high discrimination between
      geographic populations, make geometric shape a promising character for future
      taxonomic and epidemiological studies.

PMID- 27890577
TI  - Transcription factors regulating uspA genes in Catharanthus roseus.
AB  - RNA-Seq of the Catharanthus roseus SRA database was done in order to detect
      putative universal stress proteins (USPs) and their possible controlling factors.
      Previous analysis indicated the existence and characterization of uspA-like
      genes. In silico analysis of RNA-Seq database in several plant tissues revealed
      the possible functions and regulations of some uspA-like transcripts whose
      transcription factors (TFs) that might drive their expression were detected.
      BLAST indicated the existence of TF superfamilies erf (ethylene-responsive TF),
      bHLH (basic helix-loop-helix) and WRKY that might regulate several uspA-like
      genes. This data was proven via semi-quantitative RT-PCR in four plant tissues.
      Several of these transcription factor superfamilies are known for their action in
      the plant defense against biotic and abiotic stresses.

PMID- 27890578
TI  - Adult Complex Regional Pain Syndrome Type I: A Narrative Review.
AB  - : Complex regional pain syndrome type I (CRPS I) is a multifactorial painful
      disorder with a complex pathogenesis. Both peripheral and central mechanisms are
      involved. Acute CRPS I is considered to be an exaggerated inflammatory disorder;
      however, over time, because of altered function of the sympathetic nervous system
      and maladaptive neuroplasticity, CRPS I evolves into a neurological disorder.
      This review thoroughly describes the pathophysiological aspects of CRPS I and
      summarizes the potential therapeutic options. The mechanisms and targets of the
      treatment are different in the early and late stages of the disease. This current
      review builds on a previous review by this author group by deepening the role of
      the peripheral classic and neuronal inflammatory component in the acute stage of
      this painful disorder. LEVEL OF EVIDENCE: Not applicable.

PMID- 27890579
TI  - The diagnosis and management of small renal masses.

PMID- 27890580
TI  - Lipid-free apoA-I structure - Origins of model diversity.
AB  - Apolipoprotein A-I (apoA-I) is a prominent member of the exchangeable
      apolipoprotein class of proteins, capable of transitioning between lipid-bound
      and lipid-free states. It is the primary structural and functional protein of
      high density lipoprotein (HDL). Lipid-free apoA-I is critical to de novo HDL
      formation as it is the preferred substrate of the lipid transporter, ATP Binding
      Cassette Transporter A1 (ABCA1) Remaley et al. (2001) [1]. Lipid-free apoA-I is
      an important element in reverse cholesterol transport and comprehension of its
      structure is a core issue in our understanding of cholesterol metabolism.
      However, lipid-free apoA-I is highly conformationally dynamic making it a
      challenging subject for structural analysis. Over the past 20years there have
      been significant advances in overcoming the dynamic nature of lipid-free apoA-I,
      which have resulted in a multitude of proposed conformational models.

PMID- 27890581
TI  - Total hip arthroplasty using a cementless dual-mobility cup provides increased
      stability and favorable gait parameters at five years follow-up.
AB  - BACKGROUND: Rates of dislocation following primary total hip arthroplasty (THA)
      vary from 0.5 to 10%. Dual-mobility cups in THA demonstrate increased stability.
      Clinical outcomes following THA with dual-mobility cups have been reported, but
      gait has not been assessed. Therefore we performed a retrospective case control
      study to answer: (1) is gait better in patients following THA with a dual
      mobility cup than in frail, elderly patients of the same age? (2) Are clinical
      outcomes better in patients following THA with a dual-mobility cup than in frail,
      elderly patients? (3) What is the dislocation rate following THA with a dual
      mobility cup? HYPOTHESIS: We hypothesized that patients who underwent THA with a
      dual-mobility cup have a better gait compared to frail, elderly patients of the
      same age. PATIENTS AND METHODS: Twenty patients (22 hips), mean age 79.9+/-7.7
      (range, 62.3-88.3) years were assessed in this retrospective case-control series
      5.6+/-1.4 (range: 4.1-8.8) years following dual-mobility cup THA. A reference
      group consisted of 72 "frail elderly" patients in a rehabilitation hospital for
      health problems unrelated to the lower limb, with no lower limb surgery or
      neurological conditions. Temporal and spatial gait performance were measured with
      four miniature gyroscopes, mounted on each thigh and calf, while patients walked
      freely along a 30m corridor. Harris Hip Score, WOMAC, radiological outcomes, and
      dislocation rate were determined. RESULTS: All gait parameters were better in the
      dual-mobility group compared to the frail elderly group. The dual-mobility group
      had a higher cadence (100.3 steps/minute versus 75.6 steps/minute), shorter
      (relative to gait cycle time) stance (61.6% versus 67.8%), shorter (relative to
      gait cycle time) double stance (23.3% versus 36.0%), longer stride (1.13m versus
      0.80m), and faster walking speed (0.96m/s versus 0.52m/s). Range of motion of the
      shank, thigh and knee were better in the dual-mobility group. Harris Hip Score
      was 87.6+/-13.9 (range 51-100) and WOMAC score was 11.3+/-12.1 (range 0-34) in
      the THA group. We observed no dislocations. DISCUSSION: Gait patterns five years
      following THA with the dual-mobility cup were better or comparable to published
      study populations. LEVEL OF EVIDENCE: III, retrospective case-control series.

PMID- 27890582
TI  - Molecular cloning and characterization of a Perilla frutescens cytochrome P450
      enzyme that catalyzes the later steps of perillaldehyde biosynthesis.
AB  - Perilla produces the cyclohexanoid monoterpene perillaldehyde as a major
      constituent of an essential oil that is accumulated in its glandular trichomes.
      Perillaldehyde is a marker compound for quality control of soyo and has
      biological activities such as antibacterial, sedative, or vasodilatory effects.
      The predicted perillaldehyde formation involves the cyclization of geranyl
      diphosphate, hydroxylation, and oxidation, and cytochrome P450 plays a crucial
      role in perillaldehyde biosynthesis. In this study, a cytochrome P450-type enzyme
      with perillyl alcohol and perillaldehyde synthase activities was isolated by
      analyzing an expressed sequence tag library from several oil types of pure lines
      of perilla. A recombinant protein with a sequence that was highly specific for
      the type of perillaldehyde was expressed in Saccharomyces cerevisiae and
      evaluated by an in vitro enzymatic reaction. The recombinant protein catalyzed
      the hydroxylation and oxidation of limonene to perillyl alcohol and
      perillaldehyde. Cytochrome P450 limonene-7-hydroxylase cDNA from Perilla
      frutescens has been previously isolated. The cytochrome P450 isolated in this
      study shares 37% amino-acid identity with the previously isolated enzyme;
      however, it may have different characteristics.

PMID- 27890583
TI  - Ailanthusins A-G and nor-lupane triterpenoids from Ailanthus triphysa.
AB  - Bioactivity-guided chemical investigation of the CH2Cl2 and CH2Cl2MeOH extracts
      of the stem and stem bark material of Ailanthus tryphysa (Simaroubaceae) led to
      the isolation of five cycloapotirucallanes, ailanthusins A-E, two malabaricanes,
      ailanthusins F-G, and one nor-lupane triterpenoid, 29-nor-lup-1-ene-3,20-dione
      along with twenty known compounds. Their structures were elucidated through the
      application of extensive spectroscopic methods, and the structure of ailanthusin
      A was further confirmed by single crystal X-ray analysis. Several malabaricane
      derivatives were prepared from malabaricol and, together with some of the
      isolates, were evaluated for their cytotoxic activities against human cancer and
      normal cell lines.

PMID- 27890584
TI  - A sedge plant as the source of Kangaroo Island propolis rich in prenylated p
      coumarate ester and stilbenes.
AB  - Propolis samples from Kangaroo Island, South Australia, were investigated for
      chemical constituents using high-field nuclear magnetic resonance spectral
      profiling. A type of propolis was found containing a high proportion of
      prenylated hydroxystilbenes. Subsequently, the botanical origin of this type of
      propolis was identified using a beehive propolis depletion method and analysis of
      flora. Ligurian honey bees, Apis mellifera ligustica Spinola, were found to
      produce propolis from resin exuded by the Australian native sedge plant
      Lepidosperma sp. Montebello (Cyperaceae). The plants, commonly known as sword
      sedge, were found to have resin that matched with the propolis samples identified
      as the most abundant propolis type on the island containing C- and O-prenylated
      tetrahydroxystilbenes (pTHOS) in addition to a small amount of prenylated p
      coumarate. The isolation of five pTHOS not previously characterized are reported:
      (E)-4-(3-methyl-2-buten-1-yl)-3,4',5-trihydroxy-3'-methoxystilbene, (E)-2,4-bis(3
      methyl-2-buten-1-yl)-3,3',4',5-tetrahydroxystilbene, (E)-2-(3-methyl-2-buten-1
      yl)-3-(3-methyl-2-butenyloxy)-3',4',5-trihydroxystilbene, (E)-2,6-bis(3-methyl-2
      buten-1-yl)-3,3',5,5'-tetrahydroxystilbene and (E)-2,6-bis(3-methyl-2-buten-1-yl)
      3,4',5-trihydroxy-3'-methoxystilbene. A National Cancer Institute 60 human cell
      line anticancer screen of three of these compounds showed growth inhibitory
      activity. The large Australasian genus Lepidosperma is identified as a valuable
      resource for the isolation of substances with medicinal potential.

PMID- 27890585
TI  - Cadmium in vivo exposure alters stress response and endocrine-related genes in
      the freshwater snail Physa acuta. New biomarker genes in a new model organism.
AB  - The freshwater snail Physa acuta is a sensitive organism to xenobiotics that is
      appropriate for toxicity testing. Cadmium (Cd) is a heavy metal with known toxic
      effects on several organisms, which include endocrine disruption and activation
      of the cellular stress responses. There is scarce genomic information on P.
      acuta; hence, in this work, we identify several genes related to the hormonal
      system, the stress response and the detoxification system to evaluate the effects
      of Cd. The transcriptional activity of the endocrine-related genes oestrogen
      receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR),
      the heat shock proteins genes hsp70 and hsp90 and a metallothionein (MT) gene was
      analysed in P. acuta exposed to Cd. In addition, the hsp70 and hsp90 genes were
      also evaluated after heat shock treatment. Real-time reverse transcriptase
      polymerase chain reaction (qRT-PCR) analysis showed that Cd presence induced a
      significant increase in the mRNA levels of ER, ERR and RXR, suggesting a putative
      mode of action that could explain the endocrine disruptor activity of this heavy
      metal at the molecular level on Gastropoda. Moreover, the hsp70 gene was
      upregulated after 24-h Cd treatment, but the hsp90 gene expression was not
      affected. In contrast, the hsp70 and hsp90 genes were strongly upregulated during
      heat shock response. Finally, the MT gene expression showed a non-significant
      variability after Cd exposure. In conclusion, this study provides, for the first
      time, information about the effects of Cd on the endocrine system of Gastropoda
      at the molecular level and offers new putative biomarker genes that could be
      useful in ecotoxicological studies, risk assessment and bioremediation.

PMID- 27890586
TI  - Exploring the contribution of bacteriophages to antibiotic resistance.
AB  - Bacteriophages (phages) are the most abundant and diverse biological entities in
      our planet. They infect susceptible bacterial hosts into which they either
      multiply or persist. In the latter case, phages can confer new functions to their
      hosts as a result of gene transfer, thus contributing to their adaptation (short
      term) and evolution (long-term). In this regard, the role of phages on the
      dissemination of antibiotic resistance genes (ARGs) among bacterial hosts in
      natural environments has not yet been clearly resolved. Here, we carry out a
      comprehensive analysis of thirty-three viromes from different habitats to
      investigate whether phages harbor ARGs. Our results demonstrate that while human
      associated viromes do not or rarely carry ARGs, viromes from non-human sources
      (e.g. pig feces, raw sewage, and freshwater and marine environments) contain a
      large reservoir of ARGs, thus pointing out that phages could play a part on the
      spread of antibiotic resistance. Given this, the role of phages should not be
      underestimated and it should be considered when designing strategies to tackle
      the global crisis of antibiotic resistance.

PMID- 27890587
TI  - Multiple mechanisms of heavy metal tolerance are differentially expressed in
      ecotypes of Artemisia fragrans.
AB  - Artemisia fragrans is a plant species with ability of growing on heavy metal
      polluted soils. Ecotypes of this species naturally growing in polluted areas can
      accumulate and tolerate different amounts of heavy metals (HM), depending on soil
      contamination level at their origin. Heavy metal tolerance of various ecotypes
      collected from contaminated (AP, SP) and non-contaminated (BG) sites was compared
      by cultivation on a highly HM-contaminated river sediment and a non-contaminated
      agricultural control soil. Tissue-specific HM distribution was analyzed by laser
      ablation-inductively-coupled plasma-mass spectroscopy (LA-ICP-MS) and
      photosynthetic activity by non-invasive monitoring of chlorophyll fluorescence.
      Plant-mineral analysis did not reveal ecotype-differences in concentrations of
      Cd, Zn, Cu in shoots of Artemisia plants, suggesting no differential expression
      of root uptake or root to shoot translocation of HM. There was also no detectable
      rhizosphere effect on HM concentrations on the contaminated soil. However,
      despite high soil contaminations, all ecotypes accumulated Zn only in the
      concentration range of generally reported for normal growth of plants, while Cu
      and Cd concentrations were close to or even higher than the toxicity level for
      most plants. As a visible symptom of differences in HM tolerance, only the AP
      ecotype was able to enter the generative phase to complete its life cycle.
      Analysis of tissue-specific metal distribution revealed significantly lower
      concentrations of Cd in the leaf mesophyll of this ecotype, accumulating Cd
      mainly in the leaf petioles. A similar mesophyll exclusion was detectable also
      for Cu, although not associated with preferential accumulation in the leaf
      petioles. However, high mesophyll concentrations of Cd and Cu in the SP and BG
      ecotypes were associated with disturbances of the photosynthetic activity. The
      findings demonstrate differential expression of HM exclusion strategies in
      Artemisia ecotypes and suggest Cd and Cu exclusion from the photosynthetically
      active tissues as a major tolerance mechanism of the AP ecotype.

PMID- 27890588
TI  - Aerobic and resistance exercise reinforcement and discomfort tolerance predict
      meeting activity guidelines.
AB  - BACKGROUND: Understanding individual-differences of those people who do and do
      not meet physical activity recommendations could inform targets for increasing
      physical activity. Exercise reinforcement may be one such individual-level
      determinate, but it is not yet known whether those who meet activity guidelines
      have a greater relative reinforcing value (RRV) of aerobic exercise training
      (RRVAT) or resistance training (RRVRT). The predictors of RRVAT or RRVRT are also
      not yet known. PURPOSE: To determine whether individuals who meet aerobic
      activity or muscle strengthening activity guidelines have greater RRVAT or RRVRT
      and whether the preference and tolerance for exercise intensity predicts RRVAT or
      RRVRT. METHODS: Men (n=38) and women (n=50) were measured for RRVAT, RRVRT,
      minutes of vigorous physical activity, usual resistance training behavior, and
      completed the Preference for and Tolerance of the Intensity of Exercise
      Questionnaire. RESULTS: Individuals who met physical activity guidelines for
      aerobic activity and muscle strengthening activity had 58% greater RRVAT and 54%
      greater RRVRT, respectively, than those who did not meet these guidelines.
      Preference and tolerance for exercise intensity was associated (p<0.01) with
      greater RRVRT, but not RRVAT. CONCLUSION: Having greater RRV of a mode of
      exercise is associated with meeting activity guidelines for that mode of
      exercise. Discomfort tolerance during exercise is associated with greater RRV of
      resistance exercise.

PMID- 27890589
TI  - Aged mice receiving caffeine since adulthood show distinct patterns of anxiety
      related behavior.
AB  - Caffeine is the psychostimulant most consumed worldwide. Anxiogenic effects of
      caffeine have been described in adult animals with controversial findings about
      its anxiogenic potential. Besides, the effects of caffeine on anxiety with aging
      are still poorly known. In this study, adult mice (6months old) started to
      receive caffeine (0.3 and 1.0mg/mL, drinking water) during 12-14months only in
      the light cycle and at weekdays. The open field (OF) and elevated plus maze (EPM)
      testing were used to determine the effects of caffeine on anxiety-related
      behavior in adult and aged mice (18-20months old). Because aging alters synaptic
      proteins, we also evaluated SNAP-25 (as a nerve terminals marker), GFAP (as an
      astrocyte marker) and adenosine A1 and A2A receptors levels in the cortex.
      According to the OF analysis, caffeine did not change both hypolocomotion and
      anxiety with aging. However, aged mice showed less anxiety behavior in the EPM,
      but after receiving caffeine (0.3mg/mL) during adulthood they were anxious as
      adult mice. While SNAP-25 and adenosine A2A receptors increased with aging, both
      GFAP and adenosine A1 receptors were not affected. Caffeine at moderate dose
      prevented the age-related increase of the SNAP-25, with no effect on adenosine
      A2A receptors. The absence of effect for the highest dose suggests that tolerance
      to caffeine may have developed over time. Aged mice showed high responsiveness to
      the OF, being difficult to achieve any effect of caffeine. On the other hand this
      substance sustained the adult anxious behavior over time in a less stressful
      paradigm, and this effect was coincident with changes in the SNAP-25, suggesting
      the involvement of this synaptic protein in the ability of caffeine to preserve
      changes related to emotionality with aging.

PMID- 27890590
TI  - Can cleanerfish overcome temptation? A selective role for dopamine influence on
      cooperative-based decision making.
AB  - Evidence suggests that animals are selected to make accurate choices and
      prioritize goals within the constraints of a given social environment to maximize
      fitness. These decisions are mostly based on complex processes in which value is
      linked to reward and cues may carry variable incentive salience. However, the
      level in which the incentive elicited by a cue is able to shift individual
      choices should differ between individuals and neurophysiological states. Here we
      used a notorious cooperative cleanerfish species Labroides dimidiatus to probe
      for differences in the incentive motivational valences given to food cues and
      then tested for the role of the dopaminergic system in the appraisal of such
      cues. We found that cleaners differed in Pavlovian conditioned approach
      behavioural responses to reward-associated stimuli: while the majority were fast
      to engage physically with the cue plate that indicated future reward delivery
      (sign trackers), only a few took significantly more time to respond (goal
      trackers). But amongst those that were considering the sole cue attractive, we
      discovered that the dopaminergic blockage decreased their initial propensity to
      approach and touch the cue plate. Our results show that dopamine disruption
      contributes to shifting the attribution of motivational incentive from the
      predictive cue towards the actual reward and provides key insight into the
      physiological framework of cooperative-based decision making.

PMID- 27890591
TI  - Circadian waveform bifurcation, but not phase-shifting, leaves cued fear memory
      intact.
AB  - In mammals, memory acquisition and retrieval can be affected by time of day, as
      well as by manipulations of the light/dark cycle. Under bifurcation, a
      manipulation of circadian waveform, two subjective days and nights are
      experimentally induced in rodents. We examined the effect of bifurcation on
      Pavlovian fear conditioning, a prominent model of learning and memory. Here we
      demonstrate that bifurcation of the circadian waveform produces a small deficit
      in acquisition, but not on retrieval of fear memory. In contrast, repeated phase
      shifting in a simulated jet-lag protocol impairs retrieval of memory for cued
      fear. The results have implications for those attempting to adjust to shift-work
      or other challenging schedules.

PMID- 27890592
TI  - Small particle size lipid emulsions, satiety and energy intake in lean men.
AB  - Lipid emulsions have been proposed to suppress hunger and food intake. Whilst
      there is no consensus on optimal structural properties or mechanism of action,
      small particle size (small-PS) stable emulsions may have greatest efficacy.
      Fabuless(r), a commercial lipid emulsion reported in some studies to decrease
      energy intake (EI), is a small-PS, 'hard' fat emulsion comprising highly
      saturated palm oil base (PS, 82nm). To determine whether small-PS dairy lipid
      emulsions can enhance satiety, firstly, we investigated 2 'soft' fat dairy
      emulsions generated using dairy and soy emulsifying agents (PS, 114nm and 121nm)
      and a non-emulsified dairy control. Secondly, we investigated a small-PS
      palmolein based 'hard' fat emulsion (fractionated palm oil, PS, 104nm) and non
      emulsified control. This was a 6 arm, randomized, cross-over study in 18 lean
      men, with test lipids delivered in a breakfast meal: (i) Fabuless(r) emulsion
      (FEM); (ii) dairy emulsion with dairy emulsifier (DEDE); (iii) dairy emulsion
      with soy lecithin emulsifier (DESE); (iv) dairy control (DCON); (v) palmolein
      emulsion with dairy emulsifier (PEDE); (vi) palmolein control (PCON).
      Participants rated postprandial appetite sensations using visual analogue scales
      (VAS), and ad libitum energy intake (EI) was measured at a lunch meal 3.5h later.
      Dairy lipid emulsions did not significantly alter satiety ratings or change EI
      relative to dairy control (DEDE, 4035kJ; DESE, 3904kJ; DCON, 3985kJ; P>0.05) nor
      did palm oil based emulsion relative to non-emulsified control (PEDE, 3902 kJ;
      PCON, 3973kJ; P>0.05). There was no evidence that small-PS dairy lipid emulsions
      or commercial Fabuless altered short-term appetite or food intake in lean adults.

PMID- 27890593
TI  - Evaluation of the crystal structure of a fimbrillin (FimA) from Porphyromonas
      gingivalis as a therapeutic target for photo-activated disinfection with
      toluidine blue O.
AB  - BACKGROUND: Porphyromonas gingivalis is one of the etiological agents in the
      initiation of combined periodontal-endodontic (perio-endo) lesions. Successful
      treatment of perio-endo lesions with photo-activated disinfection (PAD) as a
      novel therapeutic approach depends on the selection of an appropriate target
      site, specific photosensitizer (PS), and wavelength of light. Since the
      fimbrillin (FimA) is the most important pathogenic agent in P. gingivalis it was
      evaluated as a target site against PAD with toluidine blue O (TBO) as a PS.
      MATERIALS AND METHODS: We evaluated the potential of FimA using a number of
      bioinformatic tools and computer simulation molecular modeling. In silico
      analysis was done to predict the hierarchical nature of structure, topology,
      backbone, physicochemical properties, and functional characterization of FimA.
      RESULTS: The predicted structure of FimA exhibited that it is an anionic protein
      with negative charge (-7.00) in pH7 and random coil which dominates other
      secondary structures located outside the cell. It has three motifs with seven
      ligand binding site residues and one active site residue which can be a site of
      interaction for cationic TBO. CONCLUSION: Based on the results of this study
      cationic TBO tends to interact with FimA during PAD as a major target to increase
      the efficiency of treatment of perio-endo lesions.

PMID- 27890594
TI  - An investigation of trends in precious metal and copper content of RAM modules in
      WEEE: Implications for long term recycling potential.
AB  - Precious metal (PM) and copper content of dynamic-RAM modules placed on the
      market during 1991-2008 has been analysed by AAS following comminution and acid
      digestion. Linear regression analysis of compositional data ordered according to
      sample chronology was used to identify historic temporal trends in module
      composition resulting from changes in manufacturing practices, and to project
      future trends for use in more accurate assessment of future recycling potential.
      DRAM was found to be 'high grade' waste with: stable levels of gold and silver
      over time; 80% reduction in palladium content during 1991-2008; and
      0.23g/module/year increase in copper content with a 75% projected increase from
      2008 by 2020. The accuracy of future recycling potential projections for WEEE
      using current methods based on static compositional data from current devices is
      questionable due to likely changes in future device composition. The impact on
      recycling potential projections of waste laptops, smart phones, cell phones and
      tablets arising in Europe in 2020 resulting from a 75% increase in copper content
      is considered against existing projections using static compositional data. The
      results highlight that failing to consider temporal variations in PM content may
      result in significant discrepancies between projections and future recycling
      potential.

PMID- 27890595
TI  - The formation and physical stability of two-phase solid dispersion systems of
      indomethacin in supercooled molten mixtures with different matrix formers.
AB  - Amorphous solid dispersions (SDs) are a promising approach to improve the
      dissolution rate of and oral bioavailability of poorly water-soluble drugs. In
      some cases multi-phase, instead of single-phase, SD systems with amorphous drug
      are obtained. While it is widely assumed that one-phase amorphous systems are
      desirable, two-phase systems may still potentially exhibit enhanced stability and
      dissolution advantages over undispersed systems. The objective of the present
      study was to understand the solid-state properties of two-phase SDs with
      amorphous drug and their relation to physical stability. Two different types of
      excipients for SD formation were used, one being a polymer and the other a small
      molecule excipient. The supercooled molten SDs of a poorly water-soluble
      indomethacin (IND) with a graft copolymer, Soluplus(r) (SOL) and sugar alcohol,
      xylitol (XYL) were prepared. Supercooled molten SDs of IND with SOL were two
      phase glassy suspension in which the amorphous drug was dispersed in an amorphous
      polymer matrix. A short-term aging of the SDs led to the formation of glassy
      suspensions where the crystalline drug was dispersed in an amorphous polymer
      matrix. These were physically stable at room temperature for the time period
      studied (RT, 23+/-2 degrees C), but aging at high-humidity conditions (75% RH)
      recrystallization to metastable alpha-IND occurred. Interestingly, the SDs with
      XYL were two-phase amorphous precipitation systems in which the drug was in an
      amorphous form in the crystalline sugar alcohol matrix. The SDs of IND and XYL
      exhibited fast drug recrystallization. In conclusion, the preparation method of
      two-phase systems via co-melting in association with the rapid quench cooling is
      a feasible method for the formulation of poorly water-soluble drugs. The physical
      stability of these two-phase systems, however, is dependent on the carrier
      material and storage conditions.

PMID- 27890596
TI  - Monoacyl phosphatidylcholine inhibits the formation of lipid multilamellar
      structures during in vitro lipolysis of self-emulsifying drug delivery systems.
AB  - The colloidal structures formed during lipolysis of self-emulsifying drug
      delivery systems (SEDDS) might affect the solubilisation and possibly the
      absorption of drugs. The aim of the current study is to elucidate the structures
      formed during the in vitro lipolysis of four SEDDS containing medium-chain
      glycerides and caprylocaproyl polyoxyl-8 glycerides (Labrasol), with or without
      monoacyl phosphatidylcholine (MAPC). In situ synchrotron small-angle X-ray
      scattering (SAXS) was combined with ex situ cryogenic transmission electron
      microscopy (cryo-TEM) and dynamic light scattering (DLS) to elucidate the
      generated structures. The SAXS scattering curves obtained during the lipolysis of
      MAPC-free SEDDS containing 43-60% w/w Labrasol displayed a lamellar phase peak at
      q=2.13nm-1 that increased with Labrasol concentration, suggesting the presence of
      multilamellar structures (MLS) with a d-spacing of 2.95nm. However, SEDDS
      containing 20-30% w/w MAPC did not form MLS during the lipolysis. The cryo-TEM
      and DLS studies showed that MAPC-free SEDDS formed coarse emulsions while MAPC
      containing SEDDS formed nanoemulsions during the dispersion in digestion medium.
      From the first minute and during the entire lipolysis process, SEDDS both with
      and without MAPC generated uni-, bi-, and oligo-lamellar vesicles. The lipolysis
      kinetics in the first minutes of the four SEDDS correlated with an increased
      intensity of the SAXS curves and the rapid transformation from lipid droplets to
      vesicles observed by cryo-TEM. In conclusion, the study elucidates the structures
      formed during in vitro lipolysis of SEDDS and the inhibitory effect of MAPC on
      the formation of MLS.

PMID- 27890597
TI  - Identification, eukaryotic expression and structure & function characterizations
      of beta-defensin like homologues from Pelodiscus sinensis.
AB  - Defensins are a group of host defense peptides that play a central role in host
      innate immune responses. Here, 26 genes encoding beta-defensin-like peptides have
      been identified for the first time in Pelodiscus sinensis using database mining
      approach. Phylogenetic study confirmed that beta-defensins are fast evolving
      genes with high rates of sequence substitutions. The expression level of several
      selected genes in different tissues was examined by RT-PCR. Ps-BDs mainly adopt
      beta-strands and/or alpha-helix conformations homology modeled by Rosetta
      program. Further, Ps-BD2 was expressed in Pichia pastoris and purified using Ni
      NTA column and RT-HPLC. As expected, the rPs-BD2 showed strong antimicrobial
      activity, but displayed a negligible hemolytic and cytotoxic activity on human
      erythrocytes and Raw 264.7 murine macrophage cells, respectively. Our results
      suggested that the Ps-BD2 was produced efficiently in P. pastoris expression
      system, which makes the large-scale use of rPs-BDs possible in the future
      clinical practice.

PMID- 27890598
TI  - Small and large number discrimination in goldfish (Carassius auratus) with
      extensive training.
AB  - Previous studies on relative quantity discrimination in birds and mammals with
      training procedures have employed hundreds or thousands of trials whereas studies
      with fish typically use dozens of trials. The goal of this study was to examine
      whether more extensive training improves the performance of fish tested on
      stimuli in the small (<4) and large (>4) number range. Goldfish were trained with
      dot array stimuli using the ratio 0.5 (2 vs. 4, 6 vs. 12) across two blocks of
      training sessions with a total of approximately 1200 trials. They were tested
      after each block of training sessions with the ratios 0.33 (1 vs. 3, 5 vs. 15),
      0.5 (2 vs. 4, 6 vs. 12), and 0.67 (2 vs. 3, 10 vs. 15). Performance exceeded 90%
      correct on both test blocks. Accuracy was not affected by manipulating the
      surface area, density, or space of stimuli. Performance was best on the ratio 0.5
      in test block 1, but ratio-independent in test block 2. There was no difference
      in performance in the small vs. large number range across the study. These
      results suggest that fish given extensive training can achieve accuracy on a
      numerical task comparable to well-trained birds, humans, or non-human primates.

PMID- 27890599
TI  - Adenosine in sperm physiology.
AB  - It has long been known that ATP and cAMP are deeply involved in sperm function
      whereas the role of adenosine and adenosine receptors is still far from being
      totally construed. The presence of adenosine in male reproductive tract and
      adenosine receptors on spermatozoa is strongly suggestive of a functional role of
      these receptors in sperm physiology and function. Spermatozoa are highly
      differentiated cells with fertility as the only goal. This paper, by an extensive
      review of the literature, outlines our current understanding of the role and
      effects of adenosine and adenosine receptors in spermatogenesis and in the
      acquisition of sperm fertilizing capacity which occurs in the femal genital
      tract, where the motile sperm fertilize an egg to form a zygote.

PMID- 27890600
TI  - Folate status and colorectal cancer risk: A 2016 update.
AB  - The consensus of epidemiologic evidence indicates that an abundant intake of
      foodstuffs rich in folate conveys protection against the development of
      colorectal cancer, and perhaps some other common cancers as well. Pre-clinical
      models substantiate that the relationship is a genuinely causal one. Pre-clinical
      models have also lent mechanistic insights into the biochemical and molecular
      pathways by which adequate folate exposure conveys these protective effects, and
      human studies are beginning to confirm the relevance of this mechanistic
      understanding to human cancer biology. Enhancement of genetic stability appears
      to be a major mechanism by which folate sufficiency protects against
      carcinogenesis. To date, the Wnt signaling cascade has been the pathway most
      examined in this regard. The relationship between folate exposure and colorectal
      cancer risk is a complex one, in part because a number of extrinsic and intrinsic
      factors act as effect modifiers. This review discusses how the intake of the
      other three B-vitamins integral to the 1-carbon pathway acts as one such effect
      modifier. In addition, two concepts that remain matters of considerable debate
      are whether parental intake of folate impacts on subsequent cancer risk in the
      offspring, and whether excessive intakes of folate may have a paradoxical cancer
      promoting effect: observations underlying these two concepts are presented as
      well.

PMID- 27890601
TI  - Tramadol: Effects on sexual behavior in male rats are mainly caused by its 5-HT
      reuptake blocking effects.
AB  - Tramadol is a well-known and effective analgesic. Recently it was shown that
      tramadol is also effective in human premature ejaculation. The inhibitory effect
      of tramadol on the ejaculation latency is probably due to its mechanism of action
      as a MU-opioid receptor agonist and noradrenaline/serotonin (5-HT) reuptake
      inhibitor. In order to test this speculation, we tested several doses of tramadol
      in a rat model of male sexual behavior and investigated two types of drugs
      interfering with the MU-opioid and the 5-HT system. First the MU-opioid receptor
      agonist properties of tramadol were tested with naloxone, a MU-opioid receptor
      antagonist. Second, the effects of WAY100,635, a 5-HT1A receptor antagonist, were
      tested on the behavioral effects of tramadol. Finally the effects of paroxetine,
      a selective serotonin reuptake inhibitor, combined with naloxone or WAY100,635
      treatment, were compared to the effects of tramadol combined with these drugs.
      Results showed that naloxone, at a sexually inactive dose, could only partially
      antagonize the inhibitory effect of tramadol. Moreover, low and behaviorally
      inactive doses of WAY100,635, strongly decreased sexual behavior when combined
      with a behaviorally inactive dose of tramadol. Finally we showed that the effects
      of paroxetine on sexual behavior resembled the effects of tramadol, indicating
      that tramadol's inhibitory effects on sexual behavior are primarily and mainly
      caused by its SSRI properties and that its MU-opioid receptor agonistic activity
      only contributes marginally. These findings support the hypothesis that tramadol
      exerts inhibition of premature ejaculations in men by its 5-HT reuptake
      inhibiting properties.

PMID- 27890603
TI  - A novel inhibitor of endocannabinoid catabolic enzymes sheds light on behind the
      scene interplay between chronic pain, analgesic tolerance, and heroin dependence.
AB  - From the Aristotelian ancient Greece, pain has been associated with appetites or
      emotions and is opposite to pleasure. Reward and addiction is also linked to
      pleasure and compulsive drug seeking reinstates pleasure. Alleviation of chronic
      pain can induce a euphoric phase similar to what is found in addiction. Both
      chronic pain and addiction are recognized as a disease of the central nervous
      system. They share many characteristics and brain regions/mechanisms. Evidence
      points to the usefulness of cannabinoids as a new class of agents to add to the
      pharmaceutical toolbox in the management of chronic pain. Wilkerson and
      colleagues, in this issue, examine SA-57, an inhibitor of two different
      endocannabinoid catabolic enzymes FAAH and MAGL, demonstrating its analgesic
      effectiveness and morphine-sparing properties in a chronic pain model, as well as
      its ability to reduce heroin seeking behavior in a self-administration paradigm
      in mice. This timely study emphasizes the need for development of more
      efficacious chronic pain therapeutics with minimized abuse potential and/or
      reinforcing properties. It also highlights the need for better understanding of
      the overlapping circuitry of chronic pain, reward, and addiction.

PMID- 27890602
TI  - The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive
      effects, augmented morphine-induced antinociception, and attenuated heroin
      seeking behavior in mice.
AB  - Although opioids are highly efficacious analgesics, their abuse potential and
      other untoward side effects diminish their therapeutic utility. The addition of
      non-opioid analgesics offers a promising strategy to reduce required
      antinociceptive opioid doses that concomitantly reduce opioid-related side
      effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid
      amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing
      effects in preclinical models of pain. As simultaneous inhibition of these
      enzymes elicits enhanced antinociceptive effects compared with single enzyme
      inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57
      [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2
      oxoethyl ester] produces morphine-sparing antinociceptive effects, without major
      side effects associated with either drug class. SA-57 dose-dependently reversed
      mechanical allodynia in the constriction injury (CCI) of the sciatic nerve model
      of neuropathic pain and carrageenan inflammatory pain model. As previously
      reported, SA-57 was considerably more potent in elevating anandamide (AEA) than 2
      arachidonyl glycerol (2-AG) in brain. Its anti-allodynic effects required
      cannabinoid (CB)1 and CB2 receptors; however, only CB2 receptors were necessary
      for the anti-edematous effects in the carrageenan assay. Although high doses of
      SA-57 alone were required to produce antinociception, low doses of this compound,
      which elevated AEA and did not affect 2-AG brain levels, augmented the
      antinociceptive effects of morphine, but lacked cannabimimetic side effects.
      Because of the high abuse liability of opioids and implication of the
      endocannabinoid system in the reinforcing effects of opioids, the final
      experiment tested whether SA-57 would alter heroin seeking behavior. Strikingly,
      SA-57 reduced heroin-reinforced nose poke behavior and the progressive ratio
      break point for heroin. In conclusion, the results of the present study suggest
      that inhibition of endocannabinoid degradative enzymes represents a promising
      therapeutic approach to decrease effective doses of opioids needed for clinical
      pain control, and may also possess therapeutic potential to reduce opioid abuse.

PMID- 27890604
TI  - Gender dimorphism in pediatric OSA: Is it for real?
AB  - In epidemiologic studies focused on adults, obstructive sleep apnea (OSA) has
      higher prevalence in men than in women. The evidence supporting a gender-related
      discrepant prevalence of OSA is however much more tenuous in children. Here, we
      aimed to review the evidence concerning gender- based differences in the
      prevalence of OSA in children, and if so, to examine the evidence with the intent
      to identify potential factors that may account for this putative association.
      Gender-based perception and reporting of clinical manifestations of OSA may be
      modulated by several social and cultural factors in children. Among those
      factors, gender may crucially affect the reporting of symptoms such as snoring,
      and therefore markedly skew the male:female prevalence ratios of OSA. On the
      other hand, hormonal changes associated with puberty, may be playing a role,
      albeit a relatively smaller one than previously construed. Gender bias in OSA is
      most likely due to complex interactions between several physiological and
      epidemiologic factors that are clearly operational in adults. However, the
      evidence of clear gender-based differences in OSA prevalence or severity remains
      unclear in pre-pubertal children, and may be detectable in adolescents only when
      concurrent obesity is also present. Furthermore, no published evidence emerged
      supporting increased susceptibility to OSA-related in pre-pubertal boys vs.
      girls, except in obese adolescents or in girls with elevated testosterone levels.
      Future research in OSA may give clues on the role of gender-related hormonal
      changes as a modulating factor in childhood.

PMID- 27890605
TI  - Developmental metaplasticity in neural circuit codes of firing and structure.
AB  - Firing-rate dynamics have been hypothesized to mediate inter-neural information
      transfer in the brain. While the Hebbian paradigm, relating learning and memory
      to firing activity, has put synaptic efficacy variation at the center of cortical
      plasticity, we suggest that the external expression of plasticity by changes in
      the firing-rate dynamics represents a more general notion of plasticity.
      Hypothesizing that time constants of plasticity and firing dynamics increase with
      age, and employing the filtering property of the neuron, we obtain the elementary
      code of global attractors associated with the firing-rate dynamics in each
      developmental stage. We define a neural circuit connectivity code as an
      indivisible set of circuit structures generated by membrane and synapse
      activation and silencing. Synchronous firing patterns under parameter uniformity,
      and asynchronous circuit firing are shown to be driven, respectively, by membrane
      and synapse silencing and reactivation, and maintained by the neuronal filtering
      property. Analytic, graphical and simulation representation of the discrete
      iteration maps and of the global attractor codes of neural firing rate are found
      to be consistent with previous empirical neurobiological findings, which have
      lacked, however, a specific correspondence between firing modes, time constants,
      circuit connectivity and cortical developmental stages.

PMID- 27890606
TI  - A new hyperbox selection rule and a pruning strategy for the enhanced fuzzy min
      max neural network.
AB  - In this paper, we extend our previous work on the Enhanced Fuzzy Min-Max (EFMM)
      neural network by introducing a new hyperbox selection rule and a pruning
      strategy to reduce network complexity and improve classification performance.
      Specifically, a new k-nearest hyperbox expansion rule (for selection of a new
      winning hyperbox) is first introduced to reduce the network complexity by
      avoiding the creation of too many small hyperboxes within the vicinity of the
      winning hyperbox. A pruning strategy is then deployed to further reduce the
      network complexity in the presence of noisy data. The effectiveness of the
      proposed network is evaluated using a number of benchmark data sets. The results
      compare favorably with those from other related models. The findings indicate
      that the newly introduced hyperbox winner selection rule coupled with the pruning
      strategy are useful for undertaking pattern classification problems.

PMID- 27890607
TI  - Genotype-phenotype correlations of cysteine replacement in CADASIL.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is characterized by cerebral infarction related to
      mutations in the notch homolog protein 3 (NOTCH3). We enrolled 10 patients whose
      brain magnetic resonance imaging (MRI) fluid-attenuated inversion recovery images
      showed hyperintensities (HIs) in the deep white matter and the external capsule.
      We then investigated the mutations in NOTCH3 using direct sequencing within the
      region of intron-exon boundaries in exons 2-24 of NOTCH3. Eight patients
      harboring NOTCH3 mutations (8 of 10) were identified, including a novel mutation,
      p.C162Y, and 3 cases with a sporadic form. Seven patients with cysteine
      replacement showed HI in the anterior part of the temporal lobes (ATLs), whereas
      these changes were not detected in 1 patient without cysteine replacement,
      p.R75P. Reviewing previous reports, we conclude that the patients can clearly be
      divided in 2 groups: those with cysteine replacement who showed HI in the ATL and
      those without cysteine replacement who showed no HI in the ATL. Our findings
      expand the understanding of genotype-phenotype correlations in cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

PMID- 27890608
TI  - Speciation, faunal affinities and geographical dispersal of black flies (Diptera:
      Simuliidae) in the Oriental Region.
AB  - The simuliid fauna of the Oriental Region is reviewed in comparison with those in
      five other zoogeographical regions. It is relatively young, represented by only
      one genus Simulium, which is regarded as the most specialized among 26 genera of
      the family Simuliidae. The Oriental Region has the second largest simuliid fauna
      with 524 species or 23.8% of the world total of 2204 extant species. This species
      richness is associated with a high speciation index (15.4), reflected especially
      by the high speciation rates of two dominant subgenera Gomphostilbia and Simulium
      although the number of lineages in the Oriental Region is moderate (34 or 20.6%
      of the total 165). The Oriental fauna has relationships with all other
      zoogeographical regions at the lineage level, having the highest affinity index
      (31.9) with the Palearctic Region. It is inferred that eight of 10 Oriental
      subgenera moved during the ice ages from the Palaearctic to the Oriental Regions;
      the subgenus Gomphostilbia evolved into 11 species-groups and underwent species
      radiation in the Oriental Region. On the other hand, two other subgenera,
      Nevermannia and Simulium, moved southward during the ice ages after evolving into
      species-groups. In the post-ice ages, most lineages retreated northward, with
      different portions of species left in the Oriental Region, although some lineages
      failed to retreat and survived as relict lineages in the Oriental Region.

PMID- 27890609
TI  - Engineering Dual Begomovirus-Bemisia tabaci Resistance in Plants.
AB  - The whitefly Bemisia tabaci is an important pest of many economically important
      crops and the vector of begomoviruses (family Geminiviridae). Recently, the
      expression of insecticidal proteins and/or toxins or double-stranded (ds)RNA
      homologous to B. tabaci genes has been demonstrated to provide the plant with
      protection against B. tabaci and the viruses that it transmits.

PMID- 27890610
TI  - A novel real-time PCR assay for highly specific detection and quantification of
      vaginal lactobacilli.
AB  - PCR detection and quantification of vaginal lactobacilli remains problematic
      because of the high level of genetic heterogeneity and taxonomic complexity
      within the genus Lactobacillus. The aim of the present study was to identify
      conserved sequences among the genomes of major species of vaginal lactobacilli
      that could be used for the development of a PCR-based method for quantitative
      determination of vaginal microbiota-specific lactobacilli. Comparative analysis
      of the genomes of several species of vaginal lactobacilli allowed us to identify
      conserved regions in the rplK gene, which encodes ribosomal protein L11, and to
      design group-specific PCR primers and a probe for selected species from the L.
      acidophilus complex, including major vaginal lactobacilli Lactobacillus
      crispatus, L. gasseri, L. iners and L. jensenii as well as other species that are
      less common in vaginal microbiota. The applicability of the new assay in routine
      diagnostic testing was evaluated using a set of clinical samples. The assay was
      able to detect and quantify vagina-associated lactobacilli within a wide range of
      initial DNA template concentrations, indicating promising potential for clinical
      applications.

PMID- 27890611
TI  - Histone methyltransferase Setdb1 is indispensable for Meckel's cartilage
      development.
AB  - The histone methyltransferase Setdb1 represses gene expression by catalyzing
      lysine 9 of histone H3 trimethylation. Given that the conventional knockout of
      Setdb1 is embryo-lethal at the implantation stage, its role in craniofacial
      development is poorly understood. Here, we investigated the role of Setdb1, using
      conditional knockout mice-in which Setdb1 was deleted in the Meckel's cartilage
      (Setdb1 CKO)-and the mouse chondrogenic cell line ATDC5-in which Setdb1 was
      inhibited by siRNA. Deletion of Setdb1 in Meckel's cartilage, the supportive
      tissue in the embryonic mandible, led to its enlargement, instead of the
      degeneration that normally occurs. Chondrocytes from the Meckel's cartilage of
      Setdb1 CKO mice showed increased size. Furthermore, at embryonic days 16.5 and
      18.5, part of the perichondrium was disrupted and mineralization was observed in
      the Meckel's cartilage. Proliferation analysis showed that inhibition of Setdb1
      caused increased proliferation in chondrocytes in the Meckel's cartilage as well
      as in ATDC5 cells. Quantitative RT-PCR showed decreased expression of
      chondrogenic genes, such as Sox9, Mmp13, Collagen II, and Aggrecan, as a result
      of Setdb1 inhibition in ATDC5 cells. Along with these phenomenons, SMAD-dependent
      BMP signaling was significantly increased by the loss of Setdb1 in both the
      Meckel's cartilage of Setdb1 CKO mice and ATDC5 cells. Therefore, the abnormal
      development of Meckel's cartilage in Setdb1 CKO mice is partly due to the
      enhanced SMAD-dependent BMP signaling. Overall, to our knowledge, the present
      study is the first to show that epigenetic regulation by Setdb1 is indispensable
      for the embryonic development of Meckel's cartilage.

PMID- 27890612
TI  - In vitro reconstitution and biochemical analyses of the Schizosaccharomyces pombe
      nucleosome.
AB  - Schizosaccharomyces pombe, which has a small genome but shares many physiological
      functions with higher eukaryotes, is a useful single-cell, model eukaryotic
      organism. In particular, many features concerning chromatin structure and
      dynamics, including heterochromatin, centromeres, telomeres, and DNA replication
      origins, are well conserved between S. pombe and higher eukaryotes. However, the
      S. pombe nucleosome, the fundamental structural unit of chromatin, has not been
      reconstituted in vitro. In the present study, we established the method to purify
      S. pombe histones H2A, H2B, H3, and H4, and successfully reconstituted the S.
      pombe nucleosome in vitro. Our thermal stability assay and micrococcal nuclease
      treatment assay revealed that the S. pombe nucleosome is markedly unstable and
      its DNA ends are quite accessible, as compared to the canonical human nucleosome.
      These findings are important to understand the mechanisms of epigenetic genomic
      DNA regulation in fission yeast.

PMID- 27890613
TI  - Activation of PPARgamma does not contribute to macrophage ABCA1 expression and
      ABCA1-mediated cholesterol efflux to apoAI.
AB  - Activation of macrophage ABCA1/G1 expression and cholesterol efflux is believed
      one of the mechanisms by which PPARgamma inhibits atherosclerosis. PPARgamma can
      also activate CD36 expression, a receptor for oxLDL, which may supply LXR ligands
      to activate LXR-ABCA1/G1 pathways. However, the controversial effects of
      PPARgamma on ABCA1 expression have been reported. In this study, we used
      peritoneal macrophages isolated from wild type and CD36 deficient (CD36-/-) mice
      to clarify if PPARgamma ligands can influence ABCA1 expression by CD36 function.
      We found that CD36 deficiency had no effect on cholesterol efflux and ABCA1/ABCG1
      expression at basal levels. In both cell types, PPARgamma ligands (15d-PGJ2,
      troglitazone and pioglitazone) reduced ABCA1 expression and ABCA1-mediated
      cholesterol efflux to apoAI, with most by troglitazone. LXR ligand-induced ABCA1
      expression and cholesterol efflux was attenuated by PPARgamma ligands. Associated
      with decreased ABCA1 protein levels, ABCA1 mRNA and promoter activity were
      reduced by PPARgamma ligands. Furthermore, high expressing PPARgamma reduced
      ABCA1 expression and LXR-activated ABCA1 promoter in a CD36-independent manner.
      In contrast, ABCG1 expression was induced by PPARgamma ligands while inhibited by
      PPARgamma inactivation. Taken together, our study suggests that enhancement of
      macrophage cholesterol metabolism by PPARgamma is not contributed by activating
      ABCA1 expression and ABCA1-mediated cholesterol efflux to apoAI, which is not
      involved by CD36 expression either.

PMID- 27890614
TI  - Structural insights into the binding of lauric acid to CYP107L2 from Streptomyces
      avermitilis.
AB  - Streptomyces avermitilis is an actinobacterium known to produce clinically useful
      macrolides including avermectins. CYP107L2 from S. avermitilis shares a high
      sequence similarity with the PikC (CYP107L1) from S. venezuelae. To elucidate the
      structural features of CYP107L2, we conducted biochemical and structural
      characterization of CYP107L2 from S. avermitilis. The CYP107L2 gene was cloned,
      and its recombinant protein was expressed and purified. The CYP107L2 showed a low
      spin state of heme, and the reduced form yielded the CO difference spectra with a
      maximal absorption at 449 nm. Binding of pikromycin and lauric acid yielded the
      typical type I spectra with Kd values of 4.8 +/- 0.3 and 111 +/- 9 MUM,
      respectively. However, no metabolic product was observed in the enzyme reaction.
      X-ray crystal structures of the ligand-free CYP107L2 and its complex with lauric
      acid were determined at the resolution of 2.6 and 2.5 A, respectively. CYP107L2
      showed a well-conserved CYP structure with a wide-open substrate-binding cavity.
      The lauric acid is bound mainly via hydrophobic interactions with the carboxylate
      group of lauric acid coordinated to the heme of P450. Glu-40 and Leu-382 residues
      in the CYP107L2 complex with lauric acid showed significant conformational
      changes to provide plentiful room for the lauric acid in the substrate-binding
      site.

PMID- 27890615
TI  - EGR2 is a gonadotropin-induced survival factor that controls the expression of
      IER3 in ovarian granulosa cells.
AB  - Pituitary gonadotropins are key hormones that orchestrate the growth and
      development of ovarian follicles. However, limited information is available on
      intra-ovarian factors that mediate the actions of gonadotropins. In this study,
      we identified that the early growth response 2 gene (EGR2) is a gonadotropin
      inducible gene in granulosa cells of rats and humans. Analysis of consensus EGR
      binding elements (EBEs) showed that the immediate early response 3 gene (IER3) is
      a novel transcriptional target gene of EGR2 as confirmed by the luciferase assay,
      electrophoretic mobility-shift assay (EMSA), chromatin immunoprecipitation
      (ChIP), and western blot analysis. Overexpression of EGR2 promoted survival of
      KGN human granulosa-derived cells in which IER3 acts as a mediator; knockdown of
      EGR2 induced death in KGN cells. Additionally, EGR2 was found to regulate the
      expression of myeloid cell leukemia 1 (MCL-1), which belongs to the BCL-2 family
      of proteins regulating cell survival. Thus, this study identified a novel
      signaling axis, comprised of gonadotropins-EGR2-IER3, which is important for the
      survival of granulosa cells during folliculogenesis.

PMID- 27890616
TI  - Cerium chloride stimulated controlled conversion of B-to-Z DNA in self-assembled
      nanostructures.
AB  - DNA adopts different conformation not only because of novel base pairs but also
      while interacting with inorganic or organic compounds. Self-assembled branched
      DNA (bDNA) structures or DNA origami that change conformation in response to
      environmental cues hold great promises in sensing and actuation at the nanoscale.
      Recently, the B-Z transition in DNA is being explored to design various
      nanomechanical devices. In this communication we have demonstrated that Cerium
      chloride binds to the phosphate backbone of self-assembled bDNA structure and
      induce B-to-Z transition at physiological concentration. The mechanism of
      controlled conversion from right-handed to left-handed has been assayed by
      various dye binding studies using CD and fluorescence spectroscopy. Three
      different bDNA structures have been identified to display B-Z transition. This
      approach provides a rapid and reversible means to change bDNA conformation, which
      can be used for dynamic and progressive control at the nanoscale.

PMID- 27890617
TI  - Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed
      genome engineering in human cells.
AB  - CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many
      human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides
      a potential tool to introduce multiple mutations in a genome. To mimic
      complicated genomic variants in human diseases, such as multiple gene deletions
      or mutations, two or more small guide RNAs (sgRNAs) need to be introduced all
      together. This can be achieved by separate Pol III promoters in a construct.
      However, limited enzyme sites and increased insertion size lower the efficiency
      to make a construct. Here, we report a strategy to quickly assembly multiple
      sgRNAs in one construct using a polycistronic-tRNA-gRNA (PTG) strategy. Taking
      advantage of the endogenous tRNA processing system in mammalian cells, we
      efficiently express multiple sgRNAs driven using only one Pol III promoter. Using
      an all-in-one construct carrying PTG, we disrupt the deacetylase domain in
      multiple histone deacetylases (HDACs) in human cells simultaneously. We
      demonstrate that multiple HDAC deletions significantly affect the activation of
      the Wnt-signaling pathway. Thus, this method enables to efficiently target
      multiple genes and provide a useful tool to establish mutated cells mimicking
      human diseases.

PMID- 27890618
TI  - Tracking protons from respiratory chain complexes to ATP synthase c-subunit: The
      critical role of serine and threonine residues.
AB  - F1Fo-ATP synthase is a multisubunit enzyme responsible for the synthesis of ATP.
      Among its multiple subunits (8 in E. coli, 17 in yeast S. cerevisiae, 16 in
      vertebrates), two subunits a and c are known to play a central role controlling
      the H+ flow through the inner mitochondrial membrane which allows the subsequent
      synthesis of ATP, but the pathway followed by H+ within the two proteins is still
      a matter of debate. In fact, even though the structure of ATP synthase is now
      well defined, the molecular mechanisms determining the function of both F1 and FO
      domains are still largely unknown. In this study, we propose a pathway for proton
      migration along the ATP synthase by hydrogen-bonded chain mechanism, with a key
      role of serine and threonine residues, by X-ray diffraction data on the subunit a
      of E. coli Fo.

PMID- 27890619
TI  - Primary iris leiomyoma.
AB  - Intraocular leiomyomas are uncommon and usually occur in the ciliary body.
      Primary leiomyoma of the iris is both rare and a difficult diagnosis to make,
      given melanocytic tumors are more common and may be amelanotic. The somewhat
      controversial diagnosis of iris leiomyoma requires further confirmation by
      immunohistochemistry and electron microscopy. Herein, we describe a 58-year-old
      man with a 2-mm round translucent pink lesion of the iris. The tumor was excised
      by sector iridectomy. Immunohistochemistry showed positivity for both smooth
      muscle actin and desmin and negativity for S-100, HMB45, SOX10, MelanA, CD31,
      CD34, and h-caldesmon. Epstein-Barr virus-associated smooth muscle tumor was
      excluded by chromogenic in situ hybridization-Epstein-Barr virus-encoded RNA.
      Ultrastructural analysis showed cytoplasmic myofilaments with focal fusiform
      densities and micropinocytotic vesicles. Our review of previous literature
      confirmed the unusual nature of this tumor. Primary iris leiomyoma should be
      considered in the differential of an amelanotic S-100-immunonegative iris tumor.

PMID- 27890620
TI  - Drug-induced corneal epithelial changes.
AB  - Drugs across many pharmacologic classes induce corneal epithelial changes. Many
      of these drugs have cationic amphiphilic structures, with a hydrophobic ring and
      hydrophilic cationic amine side chain that allow them to cross cell membranes.
      These drugs lead to intracellular phospholipid accumulation, often manifested in
      the cornea by vortex keratopathy, with no effect on visual acuity and few ocular
      symptoms. Other drugs, notably antineoplastic agents, produce a fine diffuse
      corneal haze, sometimes accompanied by decreased vision that can be dose
      limiting. Still other medications cause crystalline epithelial precipitation that
      might require debridement for resolution. An understanding of the variety of
      drugs involved, the multiple mechanisms responsible, and the systemic diseases
      that produce similar changes can lead to improved management strategies for
      patients with corneal epithelial deposits. In most cases, drug therapy need not
      be modified or discontinued, but if visual acuity is affected, close
      collaboration with the prescribing physician can result in determining an
      optimized dose that treats systemic disease and minimizes these deposits.
      Additionally, close monitoring might be required if the drug is also associated
      with other ocular findings, such as optic neuropathy or retinopathy.

PMID- 27890621
TI  - Nasal drug delivery: Design of a novel mucoadhesive and in situ gelling polymer.
AB  - The aim of the present study was to establish a novel polymeric excipient for
      liquid nasal dosage forms exhibiting viscosity increasing properties, improved
      mucoadhesion and stability towards oxidation in solution. In order to achieve
      this goal, 2-mercaptonicotinic acid was first coupled to l-cysteine by disulfide
      exchange reaction and after purification directly attached to the polymeric
      backbone of xanthan gum by carbodiimide mediated amide bond formation. The
      resulting conjugate was characterized with respect to the amount of coupled
      ligand, the in situ gelling behavior, mucoadhesive properties and stability
      towards oxidation. Furthermore, the influence of preactivated polymers on ciliary
      beat frequency (CBF) of porcine nasal epithelial cells was investigated. Results
      showed, that 252.52+/-20.54MUmol of the ligand was attached per gram polymer. No
      free thiol groups could be detected on the polymeric backbone indicating entire
      preactivation. Rheological investigations of polymer mucus mixtures revealed a
      1.7-fold and 2.5-fold enhanced mucoadhesion of entirely preactivated xanthan (Xan
      Cys-MNA) compared to thiolated xanthan (Xan-Cys) and unmodified xanthan (Xan).
      Tensile force evaluation reported a 2.87 and 5.11-fold higher total work of
      adhesion (TWA) as well as a 1.63 and 2.41-fold higher maximum detachement force
      of Xan-Cys-MNA compared to Xan-Cys and Xan. In the presence of H2O2 as an
      oxidizing agent Xan-Cys-MNA showed unlike Xan-Cys no increase in viscosity,
      indicating high stability towards oxidation. Addition of CaCl2 to Xan-Cys-MNA
      solutions caused a decrease in viscosity at nevertheless higher total viscosity.
      Results from CBF studies proved nasal safety for the novel conjugate. According
      to these results, entirely preactivated thiolated xanthan gum seems to be a
      promising excipient for nasal dosage forms in order to improve drug
      bioavailability.

PMID- 27890622
TI  - Multi-functional nanoparticles as theranostic agents for the treatment & imaging
      of pancreatic cancer.
AB  - : Theranostics has received considerable attention since both therapy and imaging
      modalities can be integrated into a single nanocarrier. In this study,
      fluorescent iron oxide (FIO) nanoparticles and gemcitabine (G) encapsulated
      poly(lactide-co-glycolide) (PLGA) nanospheres (PGFIO) conjugated with human
      epidermal growth factor receptor 2, (HER-2) antibody (HER-PGFIO) were prepared
      and characterized. HER-PGFIO showed the magnetic moment of 10emu/g, relaxivity
      (r2) of 773mM-1s-1 and specific absorption rate (SAR) of 183W/g. HER-PGFIO showed
      a sustained release of gemcitabine for 11days in PBS (pH 7.4). In vitro
      cytotoxicity evaluation of HER-PGFIO in 3D MIAPaCa-2 cultures showed 50%
      inhibitory concentration (IC50) of 0.11mg/mL. Subcutaneous tumor xenografts of
      MIAPaCa-2 in SCID mice were developed and the tumor regression study at the end
      of 30days showed significant tumor regression (86+/-3%) in the HER-PGFIO with
      magnetic hyperthermia (MHT) treatment group compared to control group. In vivo
      MRI imaging showed the enhanced contrast in HER-PGFIO+MHT treated group compared
      to control. HER-PGFIO showed significant tumor regression and enhanced MRI in
      treatment groups, which could be an effective nanocarrier system for the
      treatment of pancreatic cancer. STATEMENT OF SIGNIFICANCE: Combination therapies
      are best suitable to treat pancreatic cancer. Theranostics are the next
      generation therapeutics with both imaging and treatment agents encapsulated in a
      single nanocarrier. The novelty of the present work is the development of
      targeted nanocarrier that provides chemotherapy, thermotherapy and MRI imaging
      properties. The present work is the next step in developing the nanocarriers for
      pancreatic cancer treatment. Different treatment modalities embedding into a
      single nanocarrier is the biggest challenge that was achieved without
      compromising the functionality of each other. The surface modification of
      polymeric nanocarriers for antibody binding and their multifunctional abilities
      will appeal to wider audience.

PMID- 27890623
TI  - SIRT1 protects osteoblasts against particle-induced inflammatory responses and
      apoptosis in aseptic prosthesis loosening.
AB  - : We hypothesized that SIRT1 downregulation in osteoblasts induced by wear
      particles was one of the reasons for particle-induced osteolysis (PIO) in total
      joint arthroplasty failure. In the present study, the expression of SIRT1 was
      examined in osteoblasts treated with TiAl6V4 particles (TiPs) and CoCrMo
      particles (CoPs) from materials used in prosthetics and specimens from PIO animal
      models. To address whether SIRT1 downregulation triggers inflammatory responses
      and apoptosis in osteoblasts, the effect of a SIRT1 activator, resveratrol on the
      expression of inflammatory cytokines and apoptosis in particle-treated
      osteoblasts was tested. The results demonstrated that SIRT1 expression was
      significantly downregulated in particle-treated osteoblasts and PIO animal
      models. Both pharmacological activation and overexpression of SIRT1 dramatically
      reduced the particle-induced expression of inflammatory cytokines and osteoblast
      apoptosis through NF-kappaB and p53 signaling, respectively. Furthermore, in PIO
      animal models, resveratrol significantly reduced the severity of osteolysis.
      Collectively, the results of the present study indicated that SIRT1 plays a vital
      role in the pathogenesis of aseptic loosening, and further treatment targeted at
      SIRT1 possibly lead to novel approaches for prevention of aseptic prosthesis
      loosening. STATEMENT OF SIGNIFICANCE: Aseptic loosening is the most common cause
      of total hip arthroplasty (THA) and total knee arthroplasty (TKA) failure and
      revision surgery. However, there is still no effective therapeutic target in the
      clinical treatment. Besides, the underlying mechanism of aseptic loosening is
      largely unknown. The result of our study indicated that SIRT1 has the ability to
      effectively regulate the wear particle-induced inflammatory responses, apoptosis,
      osteolysis in particle-stimulated osteoblasts and particle-induced osteolysis
      animal models. Our study provides a potential target for the prevention and
      treatment of aseptic loosening and further investigated the underlying mechanism
      of aseptic loosening, which may make contribution to decrease the incidence of
      THA and TKA failure in the clinical practice.

PMID- 27890625
TI  - Pharmacological treatment optimization for stable chronic obstructive pulmonary
      disease. Proposals from the Societe de Pneumologie de Langue Francaise.
AB  - The Societe de Pneumologie de Langue Francaise proposes a decision algorithm on
      long-term pharmacological COPD treatment. A working group reviewed the literature
      published between January 2009 and May 2016. This document lays out proposals and
      not guidelines. It only focuses on pharmacological treatments except
      vaccinations, smoking cessation treatments and oxygen therapy. Any COPD
      diagnosis, based on pulmonary function tests, should lead to recommend smoking
      cessation, vaccinations, physical activity, pulmonary rehabilitation in case of
      activity limitation, and short-acting bronchodilators. Symptoms like dyspnea and
      exacerbations determine the therapeutic choices. In case of daily dyspnea and/or
      exacerbations, a long-acting bronchodilator should be suggested (beta-2 agonist,
      LABA or anticholinergics, LAMA). A clinical and lung function reevaluation is
      suggested 1 to 3 months after any treatment modification and every 3-12 months
      according to the severity of the disease. In case of persisting dyspnea, a fixed
      dose LABA+LAMA combination improves pulmonary function (FEV1), quality of life,
      dyspnea and decreases exacerbations without increasing side effects. In case of
      frequent exacerbations and a FEV1<=70%, a fixed dose long-acting bronchodilator
      combination or a LABA+ inhaled corticosteroids (ICS) combination can be proposed.
      A triple combination (LABA+LAMA+ICS) is indicated when exacerbations persist
      despite one of these combinations. Dyspnea in spite of a bronchodilator
      combination or exacerbations in spite of a triple combination should lead to
      consider other pharmacological treatments (theophylline if dyspnea, macrolides if
      exacerbations, low-dose opioids if refractory dyspnea).

PMID- 27890624
TI  - Mitochondrial cAMP prevents apoptosis modulating Sirt3 protein level and OPA1
      processing in cardiac myoblast cells.
AB  - Mitochondria, responding to a wide variety of signals, including oxidative
      stress, are critical in regulating apoptosis that plays a key role in the
      pathogenesis of a variety of cardiovascular diseases. A number of mitochondrial
      proteins and pathways have been found to be involved in the mitochondrial
      dependent apoptosis mechanism, such as optic atrophy 1 (OPA1), sirtuin 3 (Sirt3),
      deacetylase enzyme and cAMP signal. In the present work we report a network among
      OPA1, Sirt3 and cAMP in ROS-dependent apoptosis. Rat myoblastic H9c2 cell lines,
      were treated with tert-butyl hydroperoxide (t-BHP) to induce oxidative stress
      dependent apoptosis. FRET analysis revealed a selective decrease of mitochondrial
      cAMP in response to t-BHP treatment. This was associated with a decrease of Sirt3
      protein level and proteolytic processing of OPA1. Pretreatment of cells with
      permeant analogous of cAMP (8-Br-cAMP) protected the cell from apoptosis
      preventing all these events. Using H89, inhibitor of the protein kinase A (PKA),
      and protease inhibitors, evidences have been obtained that ROS-dependent
      apoptosis is associated with an alteration of mitochondrial cAMP/PKA signal that
      causes degradation/proteolysis of Sirt3 that, in turn, promotes acetylation and
      proteolytic processing of OPA1.

PMID- 27890626
TI  - The appressorium of the rice blast fungus Magnaporthe oryzae remains mitotically
      active during post-penetration hyphal growth.
AB  - To investigate the mitotic dynamics of an appressorium, we used live-cell
      confocal imaging of a fluorescence-based mitotic reporter strain of Magnaporthe
      oryzae. We present evidence that the M. oryzae appressorium remains viable and
      mitotically active well after host penetration. These results suggest the
      potential roles of the appressorium during post-penetration proliferation of
      invasive hyphae. Our studies also revealed that a mitotic appressorial nucleus
      undergoes extreme constriction and elongation as it migrates through the
      penetration peg in a manner analogous to mitosis during cell-to-cell movement of
      invasive hyphae. Understanding the mechanisms underlying these pathogen-specific
      nuclear dynamics may provide new targets for disease control.

PMID- 27890627
TI  - Nuclear dynamics during ascospore germination in Sordaria macrospora.
AB  - The ascomycete Sordaria macrospora has a long history as a model organism for
      studying fungal sexual development. Starting from an ascospore, sexual fruiting
      bodies (perithecia) develop within seven days and discharge new ascospores.
      Sexual development has been studied in detail, revealing genes required for
      perithecium formation and ascospore germination. However, the germination process
      per se has not yet been examined. Here I analyze nuclear dynamics during
      ascospore germination using a fluorescently labeled histone. Live-cell imaging
      revealed that nuclei are transported into germination vesicles that form on one
      side of the spore. Polar growth is established from these vesicles.

PMID- 27890628
TI  - MRI in all MR patients: Is this the "Gold Standard" approach?

PMID- 27890629
TI  - ApoB is superior to LDL-C or non-HDL-C as a lipid marker for predicting the
      presence and severity of atherosclerosis in female patients with myocardial
      infarction.

PMID- 27890630
TI  - Arteriovenous renal replacement therapy in end-stage left-sided heart failure
      patients has a detrimental effect on patients with impaired right ventricular
      function.
AB  - OBJECTIVE: Chronic intermittent renal replacement therapy(RRT) is an alternate
      method of decongestion for patients presenting with diuretic-resistant, end-stage
      heart failure(HF) and cardiorenal syndrome. The optimal method of vascular access
      has not been confirmed. This study investigated the 6-month outcomes of patients
      with end-stage HF after the creation of arteriovenous communications (AVC)
      compared with other means of RRT. METHODS: We treated 40 patients with chronic,
      intermittent, ambulatory RRT, of whom 15 (37.5%; Group A) underwent creation of
      AVC, and 25 (62.5%; Group B) received intraperitoneal (n=6) or internal jugular
      catheters (n=19) with the goal of achieving body weight stabilization and relief
      from congestion. RESULTS: The characteristics of the two groups were similar.
      According to Cox regression analysis, the 6-month rate of death or re
      hospitalization for HF was significantly higher in Group A (73%) than in Group B
      (44%); hazard ratio (HR): 2.58; 95% confidence interval (CI) 1.2-6.2; P=0.02.
      Over a 6-month follow-up, the cumulative survival was significantly shorter
      (P=0.03) in Group A (13.8+/-10 weeks) than in Group B (20.7+/-7 weeks). In the 15
      patients who received AVC, the only independent predictor of adverse outcome at 6
      months was serum total bilirubin concentration (HR 2.5; 95% CI 1.1-5.7, p=0.02),
      whereas in the 25 patients who underwent other means of RRT, pulmonary vascular
      resistance (PVR) was identified as a risk factor for hospitalization or death at
      1-year follow-up (HR 1.26; 95% CI 1.1-1.57, p=0.04). CONCLUSION: In patients with
      end-stage HF, the creation of AVC for intermittent RRT was followed by a
      significant increase in morbidity and mortality in comparison to the safe and
      effective placement of permanent central venous catheters. Patients with elevated
      PVR seem to comprise a group at high risk for adverse outcomes after central
      catheter insertion.

PMID- 27890632
TI  - Evidence of genotypes 1 and 3 of avian hepatitis E virus in wild birds.
AB  - Although the presence of four genotypes of avian hepatitis E virus (HEV) in
      chickens has been demonstrated, its natural host range is still barely known. In
      this study, swab samples from 626 wild birds originating from 62 bird species
      were investigated for HEV detection by molecular methods. The aim was to explore
      the cross-species infection of avian HEV and to compare the genetic diversity
      between strains infecting chicken and wild birds. In total, 8 positive samples
      from 4 different bird species (song thrush, little owl, feral pigeon and common
      buzzard) were identified and further confirmed by partial sequencing of ORF3.
      Based on a 237bp fragment of the capsid gene retrieved from 5 samples,
      phylogenetic analysis revealed the presence of avian HEV genotypes 1 and 3 in
      wild birds. The wild bird isolates shared 82.7-84.8% and 85.7-100% nucleotide
      sequence identity, respectively, to chicken isolates from the corresponding
      genotype. For two of the genotype 1 samples (14-2901 and 14-2906), from feral
      pigeons, genotype assignment could be also confirmed by phylogenetic analysis
      based on partial nucleotide sequence of the helicase gene. For the first time,
      the appearance of genotype 1 in Europe was detected, which together with close
      genetic relationship between HEVs present in chickens and wild birds indicates
      cross-species transmission.

PMID- 27890634
TI  - Pushing policy that promotes equity in active living - From the outside and from
      the inside.
AB  - This is an invited commentary article, and so no abstract is required. By way of
      a brief description, this article tells two success stories in which policies
      were changed to increase equity in active living, and identifies the keys to
      success in each case.

PMID- 27890633
TI  - Comparison analysis of microRNAs in response to EV71 and CA16 infection in human
      bronchial epithelial cells by high-throughput sequencing to reveal differential
      infective mechanisms.
AB  - Hand, foot, and mouth disease (HFMD) mainly caused by Enterovirus 71 (EV71) and
      coxsackievirus A16 (CA16) infections which presented significantly different
      clinical manifestations. Nevertheless, the factors underlying these differences
      remain unclear. Recently, the functions of microRNAs (miRNAs) in pathogen-host
      interactions have been highlighted. Here, we performed comprehensive miRNA
      profiling in EV71- and CA16-infected human bronchial epithelial (16HBE) cells at
      multiple time points using high-throughput sequencing. The results showed that
      154 known and 47 novel miRNAs exhibited remarkable differences in expression. Of
      these, 65 miRNAs, including 58 known and 7 novel miRNAs, presented opposite
      trends in EV71- and CA16-infected samples. Subsequently, we mainly focused on the
      56 known differentially expressed miRNAs by further screening for targets
      prediction. GO and pathway analysis of these targets demonstrated that 18
      biological processes, 7 molecular functions, 1 cellular component and 123
      pathways were enriched. Among these pathways, Cadherin signalling pathway, Wnt
      signalling pathway and angiogenesis showed significant alterations. The
      regulatory networks of these miRNAs with predicted targets, GOs, pathways and
      transcription factors were determined, which suggested that miRNAs displayed
      intricate regulatory mechanisms during the infection phase. Consequently, we
      specifically analysed the hierarchical GO categories of the predicted targets
      involved in adhesion. The results indicated that the distinct changes induced by
      EV71 and CA16 infection may be partly linked to airway epithelial barrier
      function. Taken together, our data provide useful insights that help elucidate
      the different host-pathogen interactions following EV71 and CA16 infection and
      might offer novel therapeutic targets for these infections.

PMID- 27890635
TI  - HOS1 Facilitates the Phytochrome B-Mediated Inhibition of PIF4 Function during
      Hypocotyl Growth in Arabidopsis.
AB  - Upon exposure to light, developing seedlings undergo photomorphogenesis, as
      illustrated by inhibition of hypocotyl elongation, cotyledon opening, and leaf
      greening. During hypocotyl photomorphogenesis, light signals are sensed by
      multiple photoreceptors, among which the red/far-red light-sensing phytochromes
      have been extensively studied. However, it is not fully understood how the
      phytochromes modulate hypocotyl growth. Here, we demonstrated that HIGH
      EXPRESSION OF OSMOTICALLY RESPONSIVE GENES 1 (HOS1), which is known to either act
      as E3 ubiquitin ligase or affect chromatin organization, inhibits the
      transcriptional activation activity of PHYTOCHROME INTERACTING FACTOR 4 (PIF4), a
      key transcription factor that promotes hypocotyl growth. Consistent with the
      negative regulatory role of HOS1 in hypocotyl growth, HOS1-defective mutants
      exhibited elongated hypocotyls in the light. Notably, phyB induces HOS1 activity
      in inhibiting PIF4 function. Taken together, these observations provide a
      molecular basis for the phyB-mediated suppression of hypocotyl growth in
      Arabidopsis.

PMID- 27890631
TI  - Evasion of host immune defenses by human papillomavirus.
AB  - A majority of human papillomavirus (HPV) infections are asymptomatic and self
      resolving in the absence of medical interventions. Various innate and adaptive
      immune responses, as well as physical barriers, have been implicated in
      controlling early HPV infections. However, if HPV overcomes these host immune
      defenses and establishes persistence in basal keratinocytes, it becomes very
      difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6,
      and E7 are important in regulating host immune responses. These oncoproteins
      dysregulate gene expression, protein-protein interactions, posttranslational
      modifications, and cellular trafficking of critical host immune modulators. In
      addition to the HPV oncoproteins, sequence variation and dinucleotide depletion
      in papillomavirus genomes has been suggested as an alternative strategy for
      evasion of host immune defenses. Since anti-HPV host immune responses are also
      considered to be important for antitumor immunity, immune dysregulation by HPV
      during virus persistence may contribute to immune suppression essential for HPV
      associated cancer progression. Here, we discuss cellular pathways dysregulated by
      HPV that allow the virus to evade various host immune defenses.

PMID- 27890636
TI  - Brassica rapa Genome 2.0: A Reference Upgrade through Sequence Re-assembly and
      Gene Re-annotation.

PMID- 27890637
TI  - Antiplasmodial activity of Heinsia crinita (Rubiaceae) and identification of new
      iridoids.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Heinsia crinita is used in traditional medicine
      for the treatment of febrile illness and erectile dysfunction. Its stem bark
      powder is found in some peripheral markets in the Democratic Republic of the
      Congo (DRC) as a remedy against malaria. Investigations were conducted on crude
      extracts of leaves, fruits and stem barks in view to validate their use and to
      determine which plant part possesses the best antiplasmodial properties.
      MATERIALS AND METHODS: Different plant parts were extracted with methanol,
      ethanol and dichloromethane. Based on the preliminary assays, the dichloromethane
      extract of the stem bark was subjected to fractionation using preparative HPLC
      system and column chromatography. This step led to the isolation of two new
      iridoids which had their structures elucidated by NMR, UV, MS and FT-IR
      spectroscopic techniques. Extracts and pure compounds were tested in vitro
      against the 3D7 strain of Plasmodium falciparum. The inhibition of the parasite
      growth was evaluated in vitro by colorimetric method (p-LDH assay) and their
      cytotoxicity evaluated in vitro against the human non-cancer fibroblast cell line
      (WI38) through WST1 assay. The in vivo antiplasmodial activity was assessed by
      the inhibition of Plasmodium berghei growth in infected mice treated with the
      ethanol extract of H. crinita stem bark at the concentrations of 200 and
      300mg/Kg/day per os, using a protocol based on the 4-d suppressive test of Peters
      and compared to a non-treated negative control group of mice (growth =100%).
      Finally the antioxidant activity of the same extract was evaluated using ABTS,
      DPPH and cell-based assays. RESULTS: A moderate in vitro antiplasmodial activity
      was observed for the dichloromethane extract of the stem bark of H. crinita (IC50
      =29.2+/-1.39ug/mL) and for the two new iridoids, lamalbide 6, 7, 8- triacetate
      (IC50 =16.39+/-0.43ug/mL) as well as for its aglycone lamiridosin 6, 7, 8
      triacetate (IC50 =0.44.56+/-1.12ug/mL). The ethanolic stem bark extract (200 and
      300mg/kg/day, oral route) showed a moderate in vivo antimalarial activity in
      Plasmodium berghei-infected mice with 27.84+/-2.75% and 48.54+/-3.76% of
      inhibition of the parasite growth, respectively (p<0.01).). This extract
      displayed high cellular antioxidant activity using dichlorofluorescein-diacetate
      (DCFDA) on HL-60 monocytes. These crude extracts and pure compounds tested at the
      higher concentration of 100ug/mL did not show any cytotoxicity against WI38
      cells. CONCLUSIONS: The results showed that H. crinita extracts possess
      antimalarial activity and contain some unusual iridoids with moderate
      antiplasmodial activity, therefore justifying to some extent its traditional use
      by the local population in DRC for this purpose. This is the first report of the
      isolation and antiplasmodial activity of these two new iridoids.

PMID- 27890638
TI  - Aberrant base excision repair pathway of oxidatively damaged DNA: Implications
      for degenerative diseases.
AB  - In cellular organisms composition of DNA is constrained to only four nucleobases
      A, G, T and C, except for minor DNA base modifications such as methylation which
      serves for defence against foreign DNA or gene expression regulation.
      Interestingly, this severe evolutionary constraint among other things demands DNA
      repair systems to discriminate between regular and modified bases. DNA
      glycosylases specifically recognize and excise damaged bases among vast majority
      of regular bases in the base excision repair (BER) pathway. However, the
      mismatched base pairs in DNA can occur from a spontaneous conversion of 5
      methylcytosine to thymine and DNA polymerase errors during replication. To
      counteract these mutagenic threats to genome stability, cells evolved special DNA
      repair systems that target the non-damaged DNA strand in a duplex to remove
      mismatched regular DNA bases. Mismatch-specific adenine- and thymine-DNA
      glycosylases (MutY/MUTYH and TDG/MBD4, respectively) initiated BER and mismatch
      repair (MMR) pathways can recognize and remove normal DNA bases in mismatched DNA
      duplexes. Importantly, in DNA repair deficient cells bacterial MutY, human TDG
      and mammalian MMR can act in the aberrant manner: MutY and TDG removes adenine
      and thymine opposite misincorporated 8-oxoguanine and damaged adenine,
      respectively, whereas MMR removes thymine opposite to O6-methylguanine. These
      unusual activities lead either to mutations or futile DNA repair, thus indicating
      that the DNA repair pathways which target non-damaged DNA strand can act in
      aberrant manner and introduce genome instability in the presence of unrepaired
      DNA lesions. Evidences accumulated showing that in addition to the accumulation
      of oxidatively damaged DNA in cells, the aberrant DNA repair can also contribute
      to cancer, brain disorders and premature senescence. For example, the aberrant
      BER and MMR pathways for oxidized guanine residues can lead to trinucleotide
      expansion that underlies Huntington's disease, a severe hereditary
      neurodegenerative syndrome. This review summarises the present knowledge about
      the aberrant DNA repair pathways for oxidized base modifications and their
      possible role in age-related diseases.

PMID- 27890639
TI  - Oxidized C5-methyl cytosine bases in DNA: 5-Hydroxymethylcytosine; 5
      formylcytosine; and 5-carboxycytosine.
AB  - Recent reports suggest that the Tet enzyme family catalytically oxidize 5
      methylcytosine in mammalian cells. The oxidation of 5-methylcytosine can result
      in three chemically distinct species - 5-hydroxymethylcytsine, 5-formylcytosine,
      and 5-carboxycytosine. While the base excision repair machinery processes 5
      formylcytosine and 5-carboxycytosine rapidly, 5-hydroxymethylcytosine is stable
      under physiological conditions. As a stable modification 5-hydroxymethylcytosine
      has a broad range of functions, from stem cell pluriopotency to tumorigenesis.
      The subsequent oxidation products, 5-formylcytosine and 5-carboxycytosine, are
      suggested to be involved in an active DNA demethylation pathway. This review
      provides an overview of the biochemistry and biology of 5-methylcytosine
      oxidation products.

PMID- 27890640
TI  - An mtDNA mutation accelerates liver aging by interfering with the ROS response
      and mitochondrial life cycle.
AB  - Mitochondrial dysfunction affects liver metabolism, but it remains unclear
      whether this interferes with normal liver aging. We investigated several
      mitochondrial pathways in hepatocytes and liver tissue from a conplastic mouse
      strain compared with the control C57BL/6NTac strain over 18 months of life. The
      C57BL/6NTac-mtNODLtJ mice differed from C57BL/6NTac mice by a point mutation in
      mitochondrial-encoded subunit 3 of cytochrome c oxidase. Young C57BL/6NTac
      mtNODLtJ mice showed reduced mitochondrial metabolism but similar reactive oxygen
      species (ROS) production to C57BL/6NTac mice. Whereas ROS increased almost
      equally up to 9 months in both strains, different mitochondrial adaptation
      strategies resulted in decreasing ROS in advanced age in C57BL/6NTac mice, but
      persistent ROS production in C57BL/6NTac-mtNODLtJ mice. Only the conplastic
      strain developed elongated mitochondrial networks with artificial loop
      structures, depressed autophagy, high mitochondrial respiration and up-regulated
      antioxidative response. Our results indicate that mtDNA mutations accelerate
      liver ballooning degeneration and carry a serious risk of premature organ aging.

PMID- 27890641
TI  - Specific point mutations in key redox enzymes are associated with chemoresistance
      in epithelial ovarian cancer.
AB  - Oxidative stress plays an important role in the pathophysiology of ovarian
      cancer. Resistance to chemotherapy presents a significant challenge for ovarian
      cancer treatment. Specific single nucleotide polymorphisms (SNPs) in key redox
      enzymes have been associated with ovarian cancer survival and progression. The
      objective of this study was to determine whether chemotherapy induces point
      mutations in key redox enzymes that lead to the acquisition of chemoresistance in
      epithelial ovarian cancer (EOC). Human EOC cell lines and their chemoresistant
      counterpart were utilized for this study. Specific SNPs in key redox enzymes were
      analyzed by TaqMan SNP Genotyping. Activities and levels of key redox enzymes
      were determined by real-time RT-PCR, ELISA and a greiss assay. Point mutations in
      key redox enzymes were introduced into sensitive EOC cells via the CRISPR/Cas9
      system. Cell viability and IC50 for cisplatin were determined by the MTT Cell
      Proliferation Assay. Data was analyzed with SPSS using Student's two-tailed t
      tests and One-way ANOVA followed by Dunnett's or Tukey's post hoc tests, p<0.05.
      Here, we demonstrate that chemoresistant EOC cells are characterized by a further
      enhancement in oxidative stress as compared to sensitive counterparts.
      Additionally, chemoresistant EOC cells manifested specific point mutations, which
      are associated with altered enzymatic activity, in key redox enzymes that are not
      detected in sensitive counterparts. Supplementation of an antioxidant was able to
      successfully sensitize EOC cells to chemotherapeutics. Causality was established
      by the induction of these point mutations in sensitive EOC cells, which resulted
      in a significant increase in the level of chemoresistance. These findings
      indicate that chemotherapy induces specific point mutations in key redox enzymes
      that contribute to the acquisition of chemoresistance in EOC cells, highlighting
      a potential novel mechanism. Identification of targets for chemoresistance with
      either biomarker and/or screening potential will have a significant impact for
      the treatment of this disease.

PMID- 27890642
TI  - Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver
      disease in mice is mediated by modulating intestinal microbiota imbalance and
      related gut-liver axis activation.
AB  - Gut microbiota is involved in obesity, metabolic syndrome and the progression of
      nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the
      flavonoid quercetin may have the ability to modulate the intestinal microbiota
      composition, suggesting a prebiotic capacity which highlights a great therapeutic
      potential in NAFLD. The present study aims to investigate benefits of
      experimental treatment with quercetin on gut microbial balance and related gut
      liver axis activation in a nutritional animal model of NAFLD associated to
      obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or
      not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the
      development of hepatic steatosis as main hepatic histological finding. Increased
      accumulation of intrahepatic lipids was associated with altered gene expression
      related to lipid metabolism, as a result of deregulation of their major
      modulators. Quercetin supplementation decreased insulin resistance and NAFLD
      activity score, by reducing the intrahepatic lipid accumulation through its
      ability to modulate lipid metabolism gene expression, cytochrome P450 2E1
      (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota
      composition was determined via 16S ribosomal RNA Illumina next-generation
      sequencing. Metagenomic studies revealed HFD-dependent differences at phylum,
      class and genus levels leading to dysbiosis, characterized by an increase in
      Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically
      increased detection of Helicobacter genus. Dysbiosis was accompanied by
      endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and
      subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like
      receptor 4 (TLR-4)-NF-kappaB signaling pathway activation was associated with
      inflammasome initiation response and reticulum stress pathway induction.
      Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR
      4 pathway induction, with subsequent inhibition of inflammasome response and
      reticulum stress pathway activation, leading to the blockage of lipid metabolism
      gene expression deregulation. Our results support the suitability of quercetin as
      a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory,
      antioxidant and prebiotic integrative response.

PMID- 27890644
TI  - Epithelial Membrane Protein 2 and beta1 integrin signaling regulate APC-mediated
      processes.
AB  - Adenomatous Polyposis Coli (APC) plays a critical role in cell motility,
      maintenance of apical-basal polarity, and epithelial morphogenesis. We previously
      demonstrated that APC loss in Madin Darby Canine Kidney (MDCK) cells increases
      cyst size and inverts polarity independent of Wnt signaling, and upregulates the
      tetraspan protein, Epithelial Membrane Protein 2 (EMP2). Herein, we show that APC
      loss increases beta1 integrin expression and migration of MDCK cells. Through 3D
      in vitro model systems and 2D migration analysis, we have depicted the molecular
      mechanism(s) by which APC influences polarity and cell motility. EMP2 knockdown
      in APC shRNA cells revealed that APC regulates apical-basal polarity and cyst
      size through EMP2. Chemical inhibition of beta1 integrin and its signaling
      components, FAK and Src, indicated that APC controls cyst size and migration, but
      not polarity, through beta1 integrin and its downstream targets. Combined, the
      current studies have identified two distinct and novel mechanisms required for
      APC to regulate polarity, cyst size, and cell migration independent of Wnt
      signaling.

PMID- 27890645
TI  - Spatial and temporal characterization of endometrial mesenchymal stem-like cells
      activity during the menstrual cycle.
AB  - The human endometrium is a highly dynamic tissue with the ability to cyclically
      regenerate during the reproductive life. Endometrial mesenchymal stem-like cells
      (eMSCs) located throughout the endometrium have shown to functionally contribute
      to endometrial regeneration. In this study we examine whether the menstrual cycle
      stage and the location in the endometrial bilayer (superficial and deep portions
      of the endometrium) has an effect on stem cell activities of eMSCs (CD140b+CD146+
      cells). Here we show the percentage and clonogenic ability of eMSCs were constant
      in the various stages of the menstrual cycle (menstrual, proliferative and
      secretory). However, eMSCs from the menstrual endometrium underwent significantly
      more rounds of self-renewal and enabled a greater total cell output than those
      from the secretory phase. Significantly more eMSCs were detected in the deeper
      portion of the endometrium compared to the superficial layer but their clonogenic
      and self-renewal activities remained similar. Our findings suggest that eMSCs are
      activated in the menstrual phase for the cyclical regeneration of the
      endometrium.

PMID- 27890646
TI  - Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for
      presumed fibroids: an updated decision analysis following the 2014 Food and Drug
      Administration safety communications.
AB  - Previous decision analyses demonstrate the safety of minimally invasive
      hysterectomy for presumed benign fibroids, accounting for the risk of occult
      leiomyosarcoma and the differential mortality risk associated with laparotomy.
      Studies published since the 2014 Food and Drug Administration safety
      communications offer updated leiomyosarcoma incidence estimates. Incorporating
      these studies suggests that mortality rates are low following hysterectomy for
      presumed benign fibroids overall, and a minimally invasive approach remains a
      safe option. Risk associated with morcellation, however, increases in women age
      >50 years due to increased leiomyosarcoma rates, an important finding for patient
      centered discussions of treatment options for fibroids.

PMID- 27890647
TI  - Reducing preterm birth by a statewide multifaceted program: an implementation
      study.
AB  - BACKGROUND: A comprehensive preterm birth prevention program was introduced in
      the state of Western Australia encompassing new clinical guidelines, an outreach
      program for health care practitioners, a public health program for women and
      their families based on print and social media, and a new clinic at the state's
      sole tertiary level perinatal center for referral of those pregnant women at
      highest risk. The initiative had the single aim of safely lowering the rate of
      preterm birth. OBJECTIVE: The objective of the study was to evaluate the outcomes
      of the initiative on the rates of preterm birth both statewide and in the single
      tertiary level perinatal referral center. STUDY DESIGN: This was a prospective
      population-based cohort study of perinatal outcomes before and after 1 full year
      of implementation of the preterm birth prevention program. RESULTS: In the state
      overall, the rate of singleton preterm birth was reduced by 7.6% and was lower
      than in any of the preceding 6 years. This reduction amounted to 196 cases
      relative to the year before the introduction of the initiative and the effect
      extended from the 28-31 week gestational age group onward. Within the tertiary
      level center, the rate of preterm birth in 2015 was also significantly lower than
      in the preceding years. CONCLUSION: A comprehensive and multifaceted preterm
      birth prevention program aimed at both health care practitioners and the general
      public, operating within the environment of a government-funded universal health
      care system can significantly lower the rate of early birth. Further research is
      now required to increase the effect and to determine the relative contributions
      of each of the interventions.

PMID- 27890648
TI  - Bupropion sustained release for pregnant smokers: a randomized, placebo
      controlled trial.
AB  - BACKGROUND: Bupropion is used to treat depression during pregnancy. However, its
      usefulness as a smoking cessation aid for pregnant women is not fully known.
      OBJECTIVE: The objective of the study was to evaluate the preliminary efficacy of
      bupropion sustained release for smoking cessation during pregnancy. STUDY DESIGN:
      We conducted a randomized, prospective, double-blind, placebo-controlled, pilot
      trial. Pregnant women who smoked daily received individualized behavior
      counseling and were randomly assigned to a 12 week, twice-a-day treatment with
      150 mg bupropion sustained release or placebo. The primary study objectives were
      to determine whether bupropion sustained release reduces nicotine withdrawal
      symptoms on the quit date and during the treatment period compared with placebo
      and whether it increases 7 day point prevalence abstinence at the end of the
      treatment period and at the end of pregnancy. RESULTS: Subjects in the bupropion
      (n = 30) and placebo (n = 35) groups were comparable in age, smoking history,
      number of daily smoked cigarettes, and nicotine dependence. After controlling for
      maternal age and race, bupropion sustained release reduced cigarette cravings
      (1.5 +/- 1.1 vs 2.1 +/- 1.2, P = .02) and total nicotine withdrawal symptoms (3.8
      +/- 4.3 vs 5.4 +/- 5.1, P = .028) during the treatment period. Administration of
      bupropion sustained release reduced tobacco exposure, as determined by levels of
      carbon monoxide in exhaled air (7.4 +/- 6.4 vs 9.1 +/- 5.8, P = .053) and
      concentrations of cotinine in urine (348 +/- 384 ng/mL vs 831 +/- 727 ng/mL, P =
      .007) and increased overall abstinence rates during treatment (19% vs 2%, P =
      .003). However, there was no significant difference in 7 day point prevalence
      abstinence rates between the 2 groups at the end of medication treatment (17% vs
      3%, P = .087) and at the end of pregnancy (10% vs 3%, P = .328). CONCLUSION:
      Individual smoking cessation counseling along with the twice-daily use of 150 mg
      bupropion sustained release increased smoking cessation rates and reduced
      cravings and total nicotine withdrawal symptoms during the treatment period.
      However, there was no significant difference in abstinence rates between groups
      at the end of medication treatment and at the end of pregnancy, likely because of
      the small sample size. A larger study is needed to confirm these findings and to
      examine the potential benefit/ risk ratio of bupropion sustained release for
      smoking cessation during pregnancy.

PMID- 27890649
TI  - The plateauing of cesarean rates in industrialized countries.

PMID- 27890643
TI  - Coordination of DNA single strand break repair.
AB  - The genetic material of all organisms is susceptible to modification. In some
      instances, these changes are programmed, such as the formation of DNA double
      strand breaks during meiotic recombination to generate gamete variety or class
      switch recombination to create antibody diversity. However, in most cases,
      genomic damage is potentially harmful to the health of the organism, contributing
      to disease and aging by promoting deleterious cellular outcomes. A proportion of
      DNA modifications are caused by exogenous agents, both physical (namely
      ultraviolet sunlight and ionizing radiation) and chemical (such as benzopyrene,
      alkylating agents, platinum compounds and psoralens), which can produce numerous
      forms of DNA damage, including a range of "simple" and helix-distorting base
      lesions, abasic sites, crosslinks and various types of phosphodiester strand
      breaks. More significant in terms of frequency are endogenous mechanisms of
      modification, which include hydrolytic disintegration of DNA chemical bonds,
      attack by reactive oxygen species and other byproducts of normal cellular
      metabolism, or incomplete or necessary enzymatic reactions (such as
      topoisomerases or repair nucleases). Both exogenous and endogenous mechanisms are
      associated with a high risk of single strand breakage, either produced directly
      or generated as intermediates of DNA repair. This review will focus upon the
      creation, consequences and resolution of single strand breaks, with a particular
      focus on two major coordinating repair proteins: poly(ADP-ribose) polymerase 1
      (PARP1) and X-ray repair cross-complementing protein 1 (XRCC1).

PMID- 27890650
TI  - DiAna, an ImageJ tool for object-based 3D co-localization and distance analysis.
AB  - We present a new plugin for ImageJ called DiAna, for Distance Analysis, which
      comes with a user-friendly interface. DiAna proposes robust and accurate 3D
      segmentation for object extraction. The plugin performs automated object-based co
      localization and distance analysis. DiAna offers an in-depth analysis of co
      localization between objects and retrieves 3D measurements including co
      localizing volumes and surfaces of contact. It also computes the distribution of
      distances between objects in 3D. With DiAna, we furthermore introduce an original
      method, which allows for estimating the statistical significance of object co
      localization. DiAna offers a complete and intuitive 3D image analysis tool for
      biologists.

PMID- 27890651
TI  - Biofilm is associated with chronic streptococcal meningoencephalitis in fish.
AB  - Biofilms are aggregates of attached microbial organisms whose existence on
      tissues is often recognised as a mechanism for the establishment of most chronic
      diseases. Herein we investigated the ability of piscine Streptococcus agalactiae,
      an important aquatic pathogen, for adaptation to this sessile lifestyle in vitro
      and in the brain of a tilapia fish model. Piscine S. agalactiae exhibited a weak
      attachment to polystyrene plates and expressed a low biofilm phenotype under the
      study conditions. Furthermore, fluorescent in situ hybridization and confocal
      laser scanning microscopy revealed discrete aggregates of attached S. agalactiae
      within brain tissues and around meningeal surfaces. They were embedded in an
      exopolysaccharide containing matrix, intractable to inflammatory response and
      showed some level of resistance to penicillin despite proven susceptibility on
      sensitivity test. Intracellular bacterial aggregates were also observed,
      moreover, antibody mediated response was not demonstrated during infection.
      Nucleated erythrocytes appear to facilitate brain invasion possibly via the
      Trojan horse mechanism leading to a granulomatous inflammation. We have
      demonstrated that biofilm is associated with persistence of S. agalactiae and the
      development of chronic meningoencephalitis in fish.

PMID- 27890652
TI  - Inhibition of ERK/MAPK suppresses avian leukosis virus subgroup A and B
      replication.
AB  - We have previously shown that the extracellular signal-regulated kinase/mitogen
      activated protein kinase (ERK/MAPK) pathway contributes to subgroup J avian
      leukosis virus (ALV-J) replication and tumorigenicity. However, a role for
      ERK/MAPK signaling in ALV-A and ALV-B replication is unknown. In this study we
      successfully constructed and recovered a recombinant form of ALV-A strain GD13-1
      which showed similarities in growth to the parental wild type virus in vitro. ALV
      subgroups J, A or B all triggered ERK2 activation in primary CEF cells. ERK/MAPK
      inhibition markedly suppressed ALV-A and ALV-B replication as shown by extremely
      low levels of viral transcription and virus protein production. This finding
      provides evidence that ERK/MAPK signaling responses play important roles in ALV
      replication and may represent novel drug targets for therapeutic intervention
      strategies.

PMID- 27890653
TI  - Recent advances in lithotripsy technology and treatment strategies: A systematic
      review update.
AB  - INTRODUCTION: Shock wave lithotripsy (SWL) is a well - established treatment
      option for urolithiasis. The technology of SWL has undergone significant changes
      in an attempt to better optimize the results while reducing failure rates. There
      are some important limitations that restrict the use of SWL. In this review, we
      aim to place these advantages and limitations in perspective, assess the current
      role of SWL, and discuss recent advances in lithotripsy technology and treatment
      strategies. METHODS: A comprehensive review was conducted to identify studies
      reporting outcomes on ESWL. We searched for literature (PubMed, Embase, Medline)
      that focused on the physics of shock waves, theories of stone disintegration, and
      studies on optimising shock wave application. Relevant articles in English
      published since 1980 were selected for inclusion. RESULTS: Efficacy has been
      shown to vary between lithotripters. To maximize stone fragmentation and reduce
      failure rates, many factors can be optimized. Factors to consider in proper
      patient selection include skin - to - stone distance and stone size. Careful
      attention to the rate of shock wave administration, proper coupling of the
      treatment head to the patient have important influences on the success of
      lithotripsy. CONCLUSION: Proper selection of patients who are expected to respond
      well to SWL, as well as attention to the technical aspects of the procedure are
      the keys to SWL success. Studies aiming to determine the mechanisms of shock wave
      action in stone breakage have begun to suggest new treatment strategies to
      improve success rates and safety.

PMID- 27890654
TI  - Sublobectomy versus lobectomy for stage I non-small cell lung cancer in the
      elderly.
AB  - OBJECTIVE: The aim of our study was to compare the operative characteristics and
      long term survival for elderly patients with stage I non-small cell lung cancer
      (NSCLC) who underwent sublobectomy versus lobectomy. METHODS: We identified 245
      consecutive elderly patients (>=65y) with pathologic stage I NSCLC who underwent
      lobectomy or sublobectomy at our institution between 2006 and 2012, and assessed
      the operative characteristics, recurrence, and survival differences between these
      approaches. RESULTS: A total of 39 patients underwent sublobectomy and 206
      patients had lobectomy. There were significantly more COPD (p = 0.046) and low
      percent of predicted FEV1 (p = 0.034) in sublobectomy patients compared to the
      lobectomy group. Sublobectomy patients had significantly shorter operating time
      (p = 0.001), less blood loss (p = 0.000), and trended toward fewer chest tube
      days (p = 0.001) and shorter hospital length of stay (p = 0.030). The 1-, 3-, and
      5-year survival rates in patients with lobectomy were 91.3, 77.7, and 64.1%,
      respectively, and has no significantly difference with those underwent
      sublobectomy (87.2, 74.4, and 61.5%, respectively, p = 0.623). Subgroups survival
      analysis showed no significant difference in the OS and DFS for patients with T <
      2 cm or %FEV1<80%, but survival after sublobectomy was worse if performed on
      patients with larger tumours (T >= 2 cm) or relatively strong lung function
      (%FEV1>=80%). CONCLUSION: We concluded that sublobectomy might achieve similar
      survival rates when compared with lobectomy in elderly stage I NSCLC patients,
      especially for patients with low %FEV1 and stage IA tumours less than 2 cm in
      diameter.

PMID- 27890655
TI  - Silver nanoparticle treatment ameliorates biliary atresia syndrome in rhesus
      rotavirus inoculated mice.
AB  - Biliary atresia (BA) is a neonatal biliary system disease closely associated with
      viral infection and bile duct inflammation. Silver nanoparticles (AgNps) have
      previously revealed antiviral and anti-inflammatory properties. In this study, we
      have investigated the effects of AgNps in the treatment of the Rhesus rotavirus
      inoculation induced BA in mice. The morphology, liver histopathology, clinical
      biochemistry examination, and inflammatory cells were analyzed in BA mice.
      Results indicated that AgNps could significantly increase the survival rate of BA
      mice, and reduce jaundice and weight lost and the liver enzymes and bilirubin
      metabolism clinical parameters were close to the normal levels. Diminished
      numbers of NK cells were observed by flow cytometry analysis and
      immunohistochemical staining. Furthermore, the viral load was reduced and
      transcripts for TGF-beta mRNA were augmented after AgNps treatment. Collectively,
      our results suggest that AgNps treatment has beneficial effects on the BA mouse
      model partially through upregulation of TGF-beta.

PMID- 27890656
TI  - Nanoparticle delivery of siRNA against TWIST to reduce drug resistance and tumor
      growth in ovarian cancer models.
AB  - Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on
      account of its late stage at diagnosis and frequency of drug resistant
      recurrences. Novel therapies to overcome these barriers are urgently needed.
      TWIST is a developmental transcription factor reactivated in cancers and linked
      to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance,
      making it a promising therapeutic target. In this work, we demonstrate the
      efficacy of TWIST siRNA (siTWIST) and two nanoparticle delivery platforms to
      reverse chemoresistance in EOC models. Polyamidoamine dendrimers and mesoporous
      silica nanoparticles (MSNs) carried siTWIST into target cells and led to
      sustained TWIST knockdown in vitro. Mice treated with cisplatin plus MSN-siTWIST
      exhibited lower tumor burden than mice treated with cisplatin alone, with most of
      the effect coming from reduction in disseminated tumors. This platform has
      potential application for overcoming the clinical challenges of metastasis and
      chemoresistance in EOC and other TWIST overexpressing cancers.

PMID- 27890657
TI  - Targeting tumor highly-expressed LAT1 transporter with amino acid-modified
      nanoparticles: Toward a novel active targeting strategy in breast cancer therapy.
AB  - Designing active targeting nanocarriers with increased cellular accumulation of
      chemotherapeutic agents is a promising strategy in cancer therapy. Herein, we
      report a novel active targeting strategy based on the large amino acid
      transporter 1 (LAT1) overexpressed in a variety of cancers. Glutamate was
      conjugated to polyoxyethylene stearate as a targeting ligand to achieve LAT1
      targeting PLGA nanoparticles. The targeting efficiency of nanoparticles was
      investigated in HeLa and MCF-7 cells. Significant increase in cellular uptake and
      cytotoxicity was observed in LAT1-targeting nanoparticles compared to the
      unmodified ones. More interestingly, the internalized LAT1 together with
      targeting nanoparticles could recycle back to the cell membrane within 3 h,
      guaranteeing sufficient transporters on cell membrane for continuous cellular
      uptake. The LAT1 targeting nanoparticles exhibited better tumor accumulation and
      antitumor effects. These results suggested that the overexpressed LAT1 on cancer
      cells holds a great potential to be a high-efficiency target for the rational
      design of active-targeting nanosystems.

PMID- 27890658
TI  - Magnetic mapping of iron in rodent spleen.
AB  - Evaluation of iron distribution and density in biological tissues is important to
      understand the pathogenesis of a variety of diseases and the fate of exogenously
      administered iron-based carriers and contrast agents. Iron distribution in
      tissues is typically characterized via histochemical (Perl's) stains or
      immunohistochemistry for ferritin, the major iron storage protein. A more
      accurate mapping of iron can be achieved via ultrastructural transmission
      electron microscopy (TEM) based techniques, which involve stringent sample
      preparation conditions. In this study, we elucidate the capability of magnetic
      force microscopy (MFM) as a label-free technique to map iron at the nanoscale
      level in rodent spleen tissue. We complemented and compared our MFM results with
      those obtained using Perl's staining and TEM. Our results show how MFM mapping
      corresponded to sizes of iron-rich lysosomes at a resolution comparable to that
      of TEM. In addition MFM is compatible with tissue sections commonly prepared for
      routine histology.

PMID- 27890660
TI  - The effects of expressive writing before or after punch biopsy on wound healing.
AB  - OBJECTIVE: Recent studies have shown that written emotional disclosure
      (expressive writing) performed in the two weeks prior to wounding improves
      healing of punch biopsy wounds. In many clinical settings, it would be more
      practical for patients to perform this intervention after wounding. The aim of
      this study was to investigate whether expressive writing could speed the healing
      of punch biopsy wounds if writing was performed after wounds were made. METHODS:
      One hundred and twenty-two healthy participants aged between 18 and 55years were
      randomly allocated to one of four groups in a 2 (intervention) by 2 (timing)
      design. Participants performed either expressive writing or neutral writing,
      either before or after receiving a 4mm punch biopsy wound. Wounds were
      photographed on day 10 (primary endpoint) and day 14 after the biopsy to measure
      epithelisation. Participants also completed questionnaires on stress and affect
      two weeks prior to the biopsy, on the day of biopsy and two weeks after biopsy.
      RESULTS: There was a significant difference in healing at day 10 between groups,
      chi2(3, N=97)=8.84, p=0.032. A significantly greater proportion of participants
      who performed expressive writing before the biopsy had fully reepithelialised
      wounds on day 10 compared to participants who performed neutral writing either
      before or after wounding, with no other significant differences between groups.
      Amongst people who wrote expressively after wounding, those who finished writing
      over the first 6days were significantly more likely to be healed at 14days than
      those who finished writing later. There were significant differences in positive
      and negative affect over the healing period between the pre and post expressive
      writing groups. CONCLUSIONS: Expressive writing can improve healing if it is
      performed prior to wounding. Performing expressive writing after wounding may be
      able to improve healing depending on the timing of writing and wound assessment.
      Expressive writing causes affect to worsen followed by subsequent improvement and
      it is important to consider this in the timing of intervention delivery. Further
      research with patient groups is required to determine the clinical relevance of
      these findings.

PMID- 27890659
TI  - RNA nanoparticles harboring annexin A2 aptamer can target ovarian cancer for
      tumor-specific doxorubicin delivery.
AB  - A novel modified nucleic acid nanoparticle harboring an annexin A2 aptamer for
      ovarian cancer cell targeting and a GC rich sequence for doxorubicin loading is
      designed and constructed. The system utilizes a highly stable three-way junction
      (3WJ) motif from phi29 packaging RNA as a core structure. A phosphorothioate
      modified DNA aptamer targeting annexin A2, Endo28, was conjugated to one arm of
      the 3WJ. The pRNA-3WJ motif retains correct folding of attached aptamer, keeping
      its functions intact. It is of significant utility for aptamer-mediated targeted
      delivery. The DNA/RNA hybrid nanoparticles remained intact after systemic
      injection in mice and strongly bound to tumors with little accumulation in
      healthy organs 6 h post-injection. The Endo28-3WJ-Sph1/Dox intercalates
      selectively enhanced toxicity to annexin A2 positive ovarian cancer cells in
      vitro. The constructed RNA/DNA hybrid nanoparticles can potentially enhance the
      therapeutic efficiency of doxorubicin at low doses for ovarian cancer treatment
      through annexin A2 targeted drug delivery.

PMID- 27890661
TI  - Studying brain-regulation of immunity with optogenetics and chemogenetics; A new
      experimental platform.
AB  - The interactions between the brain and the immune system are bidirectional.
      Nevertheless, we have far greater understanding of how the immune system affects
      the brain than how the brain affects immunity. New technological developments
      such as optogenetics and chemogenetics (using DREADDs; Designer Receptors
      Exclusively Activated by Designer Drugs) can bridge this gap in our
      understanding, as they enable an unprecedented mechanistic and systemic analysis
      of the communication between the brain and the immune system. In this review, we
      discuss new experimental approaches for revealing neuronal circuits that can
      participate in regulation of immunity. In addition, we discuss methods,
      specifically optogenetics and chemogenetics, that enable targeted neuronal
      manipulation to reveal how different brain regions affect immunity. We describe
      how these techniques can be used as an experimental platform to address
      fundamental questions in psychoneuroimmunology and to understand how neuronal
      circuits associate with different psychological states can affect physiology.

PMID- 27890662
TI  - A genetic association study of CSMD1 and CSMD2 with cognitive function.
AB  - The complement cascade plays a role in synaptic pruning and synaptic plasticity,
      which seem to be involved in cognitive functions and psychiatric disorders.
      Genetic variants in the closely related CSMD1 and CSMD2 genes, which are
      implicated in complement regulation, are associated with schizophrenia. Since
      patients with schizophrenia often show cognitive impairments, we tested whether
      variants in CSMD1 and CSMD2 are also associated with cognitive functions per se.
      We took a discovery-replication approach, using well-characterized Scandinavian
      cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for
      association with cognitive functions in the NCNG sample (Norwegian Cognitive
      NeuroGenetics; n=670). Replication testing of SNPs with p-value<0.001 (7 in CSMD1
      and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized
      Psychosis; n=1025) and the BETULA sample (Betula Longitudinal Study on aging,
      memory and dementia; n=1742). Finally, we conducted a meta-analysis of these SNPs
      using all three samples. The previously identified schizophrenia marker in CSMD1
      (SNP rs10503253) was also included. The strongest association was observed
      between the CSMD1 SNP rs2740931 and performance in immediate episodic memory (p
      value=5*10-6, minor allele A, MAF 0.48-0.49, negative direction of effect). This
      association reached the study-wide significance level (p?1.2*10-5). SNP
      rs10503253 was not significantly associated with cognitive functions in our
      samples. In conclusion, we studied n=3437 individuals and found evidence that a
      variant in CSMD1 is associated with cognitive function. Additional studies of
      larger samples with cognitive phenotypes will be needed to further clarify the
      role of CSMD1 in cognitive phenotypes in health and disease.

PMID- 27890663
TI  - Hepatitis B: A cross-sectional survey of knowledge, attitudes and practices
      amongst backpackers in Thailand.
AB  - BACKGROUND: In 2013, 200 million tourists visited countries that are endemic for
      hepatitis B virus (HBV). Backpackers are potentially at greater risk of hepatitis
      B than other travellers yet exposure to HBV remains under researched in this
      population. METHOD: A cross-sectional survey of backpackers visiting two islands
      in Thailand was performed during early 2015. Participation in activities with
      high HBV exposure risk was recorded, alongside rates of vaccination and an
      evaluation of knowledge and attitudes towards the risk of HBV. RESULTS: 1680
      questionnaires were completed and analysed; the median participant age was 24
      (range: 18-68) and 47.9% were male. 20.8% took part in activities with a high
      risk of HBV exposure. Over two-thirds of the sample were not protected against
      HBV. 24% were able to correctly identify HBV transmission methods. 44.1%
      underestimated the risk of HBV in Thailand. CONCLUSIONS: The proportion of
      backpackers participating in high-risk activities was double the level found in
      previous studies that have examined the HBV exposure risk amongst travellers to
      endemic countries. Voluntary risk activities were the largest source of potential
      exposure to HBV and rates of vaccination are low. Backpackers should be
      considered for routine vaccination and education on risk behaviours should be
      included in the pre-travel consultation.

PMID- 27890664
TI  - Do alcohol-based hand rubs reduce the incidence of acute diarrhea during military
      deployments? A prospective randomized trial.
AB  - BACKGROUND: Acute diarrhea remains a public health concern in armed forces
      deployed in tropical areas where access to water and soap is limited. This study
      aims to assess the effectiveness of alcohol-based hand rubs (ABHR) on incidence
      of diarrhea in poor hygiene conditions. METHOD: A prospective randomized trial
      was conducted between November 2014 and January 2015 among French military troops
      deployed in Africa to compare a group of soldiers receiving usual hand hygiene
      recommendations (control group), to a group of soldiers who received ABHR in
      addition to usual hand hygiene recommendations (intervention group). Data on
      diarrhea and hygiene behaviors were collected using self-questionnaires. The
      incidence rate of diarrhea episodes in groups was compared. RESULTS:
      Participation rate was 59% (236/400). The proportion of individuals who used ABHR
      was 97% in the intervention group and 62% in the control group. The overall
      incidence rate of diarrheal episodes was observed to be in the region of 60 per
      100 persons-month without any significant difference between groups after
      adjustment on confounding factors (p = 0.93). Handwashing with soap was used on
      average 4 times a day in the control group and twice a day in the intervention
      group (p = 0.93). It was the only significant protective factor for diarrhea (p <
      10-3). CONCLUSION: Our results support that supplying soap and good quality water
      should be a priority on the field.

PMID- 27890665
TI  - Antibiotic resistance and international travel: Causes and consequences.

PMID- 27890666
TI  - When less is best - Why non U.S. born patients could have less MRSA.

PMID- 27890667
TI  - Investigation of carbapenem resistance and the first identification of Klebsiella
      pneumoniae carbapenemase (KPC) enzyme among Escherichia coli isolates in Turkey:
      A prospective study.
AB  - BACKGROUND: The aim of this study was to determine the presence of carbapenem
      resistance and carbapenemase production in Escherichia coli isolates from
      clinical samples in Turkey. METHODS: The prospective study included a total of
      4.052 Escherichia coli isolates collected from patients admitted to a hospital
      from March 2011 to May 2012. We used ertapenem disc for screening carbapenemase
      production, and the confirmation was performed by using Etest. The resistance
      mechanisms and genetic relatedness of the carbapenem resistant strains were
      investigated by using PCR (polymerase chain reaction) and pulsed-field gel
      electrophoresis (PFGE), respectively. RESULTS: Among the 4.052 E. coli isolates,
      24 (0.59%) were found to be carbapenem resistant. Of these, only 5 isolates were
      positive for OXA-48 and 2 isolates were positive for Klebsiella pneumoniae
      carbapenemase (KPC)-2. The KPC-2 producing E. coli strains (n = 2) were both
      isolated from the same patient. The blaKPC genes were confirmed using DNA
      sequence analysis. The genetic relationship between the 24 E. coli strains
      studied by PFGE revealed that the strains were genetically unrelated.
      CONCLUSIONS: This article confirms, to our knowledge for the first time, the
      detection of KPC-2-producing E. coli in Turkey, with OXA-48 being the most
      frequent carbapenemase in the study.

PMID- 27890668
TI  - The next generation of antimicrobial peptides (AMPs) as molecular therapeutic
      tools for the treatment of diseases with social and economic impacts.
AB  - Anti-infective drugs have had a key role in the contemporary world, contributing
      to dramatically decrease mortality rates caused by infectious diseases worldwide.
      Antimicrobial peptides (AMPs) are multifunctional effectors of the innate immune
      system of mucosal surfaces and present antimicrobial activity against a range of
      pathogenic viruses, bacteria, and fungi. However, the discovery and development
      of new antibacterial drugs is a crucial step to overcome the great challenge
      posed by the emergence of antibiotic resistance. In this review, we outline
      recent advances in the development of novel AMPs with improved antimicrobial
      activities that were achieved through characteristic structural design. In
      addition, we describe recent progress made to overcome some of the major
      limitations that have hindered peptide biosynthesis.

PMID- 27890669
TI  - Doxorubicin: nanotechnological overviews from bench to bedside.
AB  - Doxorubicin (DOX) is considered one of the most effective chemotherapeutic
      agents, used as a first-line drug in numerous types of cancer. Nevertheless, it
      exhibits serious adverse effects, such as lethal cardiotoxicity and dose-limiting
      myelosuppression. In this review, we focus on the description and the clinical
      benefits of different DOX-loaded nanotechnological platforms, not only those
      commercially available but also the ones that are currently in clinical phases,
      such as liposomes, polymeric nanoparticles, polymer-drug conjugates, polymeric
      micelles and ligand-based DOX-loaded nanoformulations. Although some DOX-based
      nanoproducts are currently being used in the clinical field, it is clear that
      further research is necessary to achieve improvements in cancer therapeutics.

PMID- 27890670
TI  - Updating molecular properties during early drug discovery.
AB  - Current multiparameter optimization (MPO) strategies make use of few experimental
      physicochemical descriptors (i.e., solubility at physiological pH and
      lipophilicity in the octanol/water system). Here, we show how new trends in drug
      discovery (i.e., large and flexible molecules for 'difficult' targets) call for
      the integration of ad hoc descriptors in MPO approaches. In particular, to rank,
      select, and optimize drug candidates, it could be relevant to have experimental
      data relating to the acid-base properties and the folding of the molecule to mask
      polar groups (so-called 'chameleonic' properties). We propose two strategies to
      quantify ionization and chameleonic properties and discuss their practical
      integration in property criteria profiles.

PMID- 27890671
TI  - Target-based approaches for the discovery of new antimycobacterial drugs.
AB  - Tuberculosis (TB) is a major global health problem and control of the disease is
      hampered by the increasing emergence of multidrug resistance (MDR) strains. Novel
      drugs are urgently needed to overcome drug resistance. Among the most relevant
      targets of the past 3 years, herein we consider nine enzymes that have been
      studied in a target-based approach. These targets are involved mainly in the
      biosynthesis of the cell wall, alpha-glucan, coenzyme A and acyl carrier protein
      precursor, and in energy production, DNA metabolism, and pyrimidine synthesis.
      Some leads and many hits have been discovered using a target-based approach and
      can be further developed in a drug discovery process.

PMID- 27890672
TI  - Epigenetics of cell fate reprogramming and its implications for neurological
      disorders modelling.
AB  - The reprogramming of human induced pluripotent stem cells (hiPSCs) proceeds in a
      stepwise manner with reprogramming factors binding and epigenetic composition
      changes during transition to maintain the epigenetic landscape, important for
      pluripotency. There arises a question as to whether the aberrant epigenetic state
      after reprogramming leads to epigenetic defects in induced stem cells causing
      unpredictable long term effects in differentiated cells. In this review, we
      present a comprehensive view of epigenetic alterations accompanying
      reprogramming, cell maintenance and differentiation as factors that influence
      applications of hiPSCs in stem cell based technologies. We conclude that sample
      heterogeneity masks DNA methylation signatures in subpopulations of cells and
      thus believe that beside a genetic evaluation, extensive epigenomic screening
      should become a standard procedure to ensure hiPSCs state before they are used
      for genome editing and differentiation into neurons of interest. In particular,
      we suggest that exploitation of the single-cell composition of the epigenome will
      provide important insights into heterogeneity within hiPSCs subpopulations to
      fast forward development of reliable hiPSC-based analytical platforms in
      neurological disorders modelling and before completed hiPSC technology will be
      implemented in clinical approaches.

PMID- 27890673
TI  - Functional validation of ABHD12 mutations in the neurodegenerative disease PHARC.
AB  - ABHD12 mutations have been linked to neurodegenerative PHARC (polyneuropathy,
      hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract), a rare,
      progressive, autosomal, recessive disease. Although ABHD12 is suspected to play a
      role in the lysophosphatidylserine and/or endocannabinoid pathways, its precise
      functional role(s) leading to PHARC disease had not previously been
      characterized. Cell and zebrafish models were designed to demonstrate the causal
      link between an identified new missense mutation p.T253R, characterized in ABHD12
      from a young patient, the previously characterized p.T202I and p.R352* mutations,
      and the associated PHARC. Measuring ABHD12 monoacylglycerol lipase activity in
      transfected HEK293 cells demonstrated inhibition with mutated isoforms. Both the
      expression pattern of zebrafish abhd12 and the phenotype of specific antisense
      morpholino oligonucleotide gene knockdown morphants were consistent with human
      PHARC hallmarks. High abhd12 transcript levels were found in the optic tectum and
      tract, colocalized with myelin basic protein, and in the spinal cord. Morphants
      have myelination defects and concomitant functional deficits, characterized by
      progressive ataxia and motor skill impairment. A disruption of retina
      architecture and retinotectal projections was observed, together with an
      inhibition of lens clarification and a low number of mechanosensory hair cells in
      the inner ear and lateral line system. The severe phenotypes in abhd12 knockdown
      morphants were rescued by introducing wild-type human ABHD12 mRNA, but not by
      mutation-harboring mRNAs. Zebrafish may provide a suitable vertebrate model for
      ABHD12 insufficiency and the study of functional impairment and potential
      therapeutic rescue of this rare, neurodegenerative disease.

PMID- 27890674
TI  - Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection
      with equine immunoglobulin or immunoglobulin fragments in a mouse model.
AB  - Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection
      caused by a coronavirus (CoV), MERS-CoV. With the continuing spread of MERS-CoV,
      prophylactic and therapeutic treatments are urgently needed. In this study, we
      prepared purified equine F(ab')2 from horses immunized with MERS-CoV virus-like
      particles (VLPs) expressing MERS-CoV S, M and E proteins. Both IgG and F(ab')2
      efficiently neutralized MERS-CoV replication in tissue culture. Passive transfer
      of equine immune antibodies significantly reduced virus titers and accelerated
      virus clearance from the lungs of MERS-CoV infected mice. Our data show that
      horses immunized with MERS-CoV VLPs can serve as a primary source of protective
      F(ab')2 for potential use in the prophylactic or therapeutic treatment of exposed
      or infected patients.

PMID- 27890675
TI  - Synergistic drug combination effectively blocks Ebola virus infection.
AB  - Although a group of FDA-approved drugs were previously identified with activity
      against Ebola virus (EBOV), most of them are not clinically useful because their
      human blood concentrations are not high enough to inhibit EBOV infection. We
      screened 795 unique three-drug combinations in an EBOV entry assay. Two sets of
      three-drug combinations, toremifene-mefloquine-posaconazole and toremifene
      clarithromycin-posaconazole, were identified that effectively blocked EBOV entry
      and were further validated for inhibition of live EBOV infection. The individual
      drug concentrations in the combinations were reduced to clinically relevant
      levels. We identified mechanisms of action of these drugs: functional inhibitions
      of Niemann-Pick C1, acid sphingomyelinase, and lysosomal calcium release. Our
      findings identify the drug combinations with potential to treat EBOV infection.

PMID- 27890676
TI  - Combined in vitro and in silico approaches to the assessment of stimulant
      properties of novel psychoactive substances - The case of the benzofuran 5-MAPB.
AB  - Novel psychoactive substances (NPS) are increasingly prevalent world-wide
      although their pharmacological characteristics are largely unknown; those with
      stimulant properties, due to interactions with the dopamine transporter (DAT),
      have addictive potential which their users may not realise. We evaluated the
      binding of 1-(1-benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB) to rat striatal
      DAT by means of quantitative autoradiography with [125I]RTI-121, and the effects
      of 5-MAPB on electrically-evoked dopamine efflux by fast-cyclic voltammetry in
      rat brain slices. 5-MAPB displaced [125I]RTI-121 in a concentration-dependent
      manner, with significant effects at 10 and 30MUM. The voltammetry data suggest
      that 5-MAPB reduces the rate of dopamine reuptake; while the peak dopamine efflux
      was not increased, the area under the curve was augmented. 5-MAPB can also cause
      reverse dopamine transport consistent with stimulant properties, more similar to
      amphetamine than cocaine. Molecular modelling and docking studies compared the
      binding site of DAT in complex with 5-MAPB to dopamine, amphetamine, 5-APB, MDMA,
      cocaine and RTI-121. This structural comparison reveals a binding mode for 5-MAPB
      found in the primary binding (S1) site, central to transmembrane domains 1, 3, 6
      and 8, which overlaps with the binding modes of dopamine, cocaine and its
      analogues. Atomistic molecular dynamics simulations further show that, when in
      complex with 5-MAPB, DAT can exhibit conformational transitions that
      spontaneously isomerize the transporter into inward-facing state, similarly to
      that observed in dopamine-bound DAT. These novel insights, offered by the
      combination of computational methods of biophysics with neurobiological
      procedures, provide structural context for NPS at DAT and relate them with their
      functional properties at DAT as the molecular target of stimulants.

PMID- 27890677
TI  - Time course of organ of Corti degeneration after noise exposure.
AB  - From our permanent collection of plastic-embedded flat preparations of chinchilla
      cochleae, 22 controls and 199 ears from noise-exposed animals were used to
      determine when, postexposure, hair cell (HC) and supporting cell (SC)
      degeneration were completed. The exposed ears were divided into four groups based
      on exposure parameters: 0.5- or 4-kHz octave band of noise at moderate (M) or
      high (H) intensities. Postexposure survival ranged from <1 h to 2.5 y. Ears fixed
      <= 0-12 h postexposure were called 'acute'. For 'chronic' ears, postexposure
      survival was >=7 d for groups 0.5M and 4M, >= 1 mo for the 4H group and >=7 mo
      for the 0.5H group. The time course of inner-ear degeneration after noise
      exposure was determined from data in the 0.5H and 4H groups because these groups
      contained ears with intermediate survival times. Outer hair cells (OHCs) began
      dying during the exposure. OHC loss slowed down beyond 1 mo but was still
      present. Conversely, much inner hair cell loss was delayed until 1-3 wk
      postexposure. Outer pillar and inner pillar losses were present at a low level in
      acute ears but increased exponentially thereafter. These results are the first to
      demonstrate quantitatively that hair cells (HCs) and supporting cells (SCs) may
      continue to degenerate for months postexposure. With short postexposure
      survivals, the remaining SCs often had pathological changes, including: buckled
      pillar bodies, shifted Deiters' cell (DC) nuclei, detachment of DCs from the
      basilar membrane and/or splitting of the reticular lamina. These pathological
      changes appeared to allow endolymph and perilymph to intermix in the fluid spaces
      of the organ of Corti, damaging additional HCs, SCs and nerve fibers. This
      mechanism may account for some postexposure degeneration. In ears exposed to
      moderate noise, some of these SC changes appeared to be reversible. In ears
      exposed to high-level noise, these changes appeared to indicate impending
      degeneration.

PMID- 27890678
TI  - Hot spot mapping of protein surfaces with TEMPOL: Bovine pancreatic RNase A as a
      model system.
AB  - TEMPOL spin-label has been used to identify surface exposure of protein nuclei
      from NMR analysis of the induced paramagnetic relaxation enhancements (PRE). The
      absence of linear dependence between atom depths and observed PRE reveals that
      specific mechanisms drive the approach of the paramagnet to the protein surface.
      RNase A represents a unique protein system to explore the fine details of the
      information offered by TEMPOL induced PRE, due to the abundance of previous
      results, obtained in solution and in the crystal, dealing with surface dynamics
      behavior of this protein. MD simulations in explicit solvent have been performed,
      also in the presence of TEMPOL, in order to delineate the role of intermolecular
      hydrogen bonds (HB) on PRE extents. Comparison of our results with the ones
      obtained from multiple solvent crystal structure (MSCS) studies yields
      information on the specificities that these two techniques have for
      characterizing protein-ligand interactions, a fundamental step in the development
      of reliable surface druggability predictors.

PMID- 27890679
TI  - Evaluation of non-supervised MALDI mass spectrometry imaging combined with
      microproteomics for glioma grade III classification.
AB  - An integrated diagnosis using molecular features is recommended in the 2016 World
      Health Organization (WHO) classification. Our aim was to explore non-targeted
      molecular classification using MALDI mass spectrometry imaging (MALDI MSI)
      associated to microproteomics in order to classify anaplastic glioma by
      integration of clinical data. We used fresh-frozen tissue sections to perform
      MALDI MSI of proteins based on their digestion peptides after in-situ trypsin
      digestion of the tissue sections and matrix deposition by micro-spraying. The
      generated 70MUm spatial resolution image datasets were further processed by
      individual or global segmentation in order to cluster the tissues according to
      their molecular protein signature. The clustering gives 3 main distinct groups.
      Within the tissues the ROIs (regions of interest) defined by these groups were
      used for microproteomics by micro-extraction of the tryptic peptides after on
      tissue enzymatic digestion. More than 2500 proteins including 22 alternative
      proteins (AltProt) are identified by the Shotgun microproteomics. Statistical
      analysis on the basis of the label free quantification of the proteins shows a
      similar classification to the MALDI MSI segmentation into 3 groups. Functional
      analysis performed on each group reveals sub-networks related to neoplasia for
      group 1, glioma with inflammation for group 2 and neurogenesis for group 3. This
      demonstrates the interest on these new non-targeted large molecular data
      combining both MALDI MSI and microproteomics data, for tumor classification. This
      analysis provides new insights into grade III glioma organization. This specific
      information could allow a more accurate classification of the biopsies according
      to the prognosis and the identification of potential new targeted therapeutic
      options. This article is part of a Special Issue entitled: MALDI Imaging, edited
      by Dr. Corinna Henkel and Prof. Peter Hoffmann.

PMID- 27890680
TI  - The putative role of MALDI-MSI in the study of Membranous Nephropathy.
AB  - Membranous Nephropathy (MN) is an immunocomplex mediated renal disease that
      represents one of the most frequent glomerulopathies worldwide. This glomerular
      disease can manifest as primary (idiopathic) or secondary and this distinction is
      crucial when choosing the most appropriate course of treatment. In secondary
      cases, the best strategy involves treating the underlying disease, whereas in
      primary forms, the identification of confirmatory markers of the idiopathic
      etiology underlining the process is requested by clinicians. Among those
      currently reported, the positivity to circulating antigens (PLA2R, IgG4 and
      THSD7A) was demonstrated in approximately 75% of iMN patients, while
      approximately 1 in 4 patients with iMN still lack a putative diagnostic marker.
      Ultimately, the discovery of biomarkers to help further stratify these two
      different forms of glomerulopathy seems mandatory. Here, MALDI-MSI was applied to
      FFPE renal biopsies from histologically diagnosed primary and secondary MN
      patients (n=20) in order to detect alterations in their tissue proteome. MALDI
      MSI was able to generate molecular signatures of primary and secondary MN, with
      one particular signal (m/z 1459), identified as Serine/threonine-protein kinase
      MRCK gamma, being over-expressed in the glomeruli of primary MN patients with
      respect to secondary MN. Furthermore, a number of signals that could
      differentiate the different forms of iMN that were positive to PLA2R or IgG4 were
      detected, as well as a further set of signals (m/z 1094, 1116, 1381 and 1459)
      that could distinguish these patients from those who were negative to both. These
      signals could potentially represent future targets for the further stratification
      of iMN patients. This article is part of a Special Issue entitled: MALDI Imaging,
      edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

PMID- 27890681
TI  - Continent Anal Urinary Diversion in Classic Bladder Exstrophy: 45-Year
      Experience.
AB  - OBJECTIVE: To evaluate the long-term outcomes in patients with classic bladder
      exstrophy and continent anal urinary diversion (CAD) for continence, upper
      urinary tract status, secondary malignancies, and sexual function. PATIENTS AND
      METHODS: The medical records of 82 exstrophy patients having undergone CAD in our
      department between 1970 and 2015 were reviewed. Patients were invited for follow
      up examinations and asked to complete validated questionnaires relating to sexual
      function. RESULTS: Thirty-two of 57 eligible patients with a median follow-up of
      23.9 years were included in the study. Ninety-seven percent of patients were
      fully continent during daytime. Upper urinary tract and renal function remained
      stable in 75% and 87%, respectively. Five patients developed secondary
      malignancies originating from the rectal reservoir. Forty-one percent received
      prophylactic alkaline substitution. Sexual function as measured by the Female
      Sexual Function Index and the International Index on Erectile Function was
      negatively affected in all domains in both genders. Eighty-six percent of
      patients had a stable relationship and 35% were married. Five women conceived a
      total of 6 healthy children. Paternity rate was 40%. CONCLUSION: CAD constitutes
      an effective treatment option with acceptable long-term outcomes in exstrophy
      patients in whom all attempts at restoring the lower urinary tract have failed.
      Long-term follow-up of the upper urinary tract, assessment of acid-base balance,
      and endoscopy of the rectosigmoid reservoir are paramount for the safety of this
      type of management. Evaluation of sexual dysfunction should be an active part of
      follow-up.

PMID- 27890682
TI  - Implementation of Dynamically Updated Prediction Models at the Point of Care at a
      Major Cancer Center: Making Nomograms More Like Netflix.

PMID- 27890683
TI  - The Effect of Obesity on Perioperative Outcomes for Open and Minimally Invasive
      Prostatectomy.
AB  - OBJECTIVE: To compare the impact of obesity on perioperative outcomes between
      open radical prostatectomy (ORP) and minimally invasive prostatectomy (MIP).
      METHODS: Using the National Surgical Quality Improvement Program public use files
      for 2008-2013, we identified patients undergoing prostatectomy using Current
      Procedural Terminology codes. Those without body mass index (BMI) or comorbidity
      information were excluded. BMI was treated as a categorical variable according to
      the World Health Organization classification. Demographic and comorbid conditions
      were compared between BMI groups, and multivariable logistical regression was
      used to identify independent predictors of adverse perioperative events. RESULTS:
      We identified 17,693 MIP and 4674 ORP for analysis. Of the entire cohort, only
      18.7% had a BMI within the normal range (18.5-24.9), whereas the remaining 81.3%
      were at least overweight (BMI > 25). Class I, II, and III obesity accounted for
      25.0%, 7.0%, and 2.3% of the cohort, respectively. Overall, complications were
      higher with ORP (19.0%) than with MIP (5.3%), which held true across all BMI
      categories. The rate of wound, renal, thromboembolic, infectious, neurologic,
      Clavien grade III-V, and overall complications among MIP were directly related to
      BMI. Only wound and renal complications were related to BMI in ORP. In
      multivariable analysis, obesity was found to be an independent predictor of
      wound, renal, and thromboembolic complications. CONCLUSION: Obesity has a larger
      impact on morbidity for MIP compared to ORP. Overall morbidity, however, remains
      lower for MIP across all BMI groups.

PMID- 27890684
TI  - Reply by the Authors.

PMID- 27890685
TI  - Bilateral Transvesicoscopic Cross-trigonal Ureteric Reimplantation in Children:
      Surgical Subtleties and a Prospective Summary.
AB  - OBJECTIVE: To prospectively evaluate the surgical technique and results of
      bilateral transvesicoscopic cross-trigonal ureteric reimplantation (TVUR) in
      children with vesicoureteric reflux (VUR) and compare the results and surgical
      subtleties with the existing literature. MATERIALS AND METHODS: From January 2010
      to December 2015, children between 2 and 14 years of age with bilateral primary
      VUR grades II-IV underwent bilateral TVUR at a tertiary referral center in
      Northern India. The grade of VUR was II in 12 patients, III in 19 patients, and
      IV in 3 patients. All surgeries were performed by a single surgeon. Success was
      defined as the absence of VUR on direct radionuclide cystogram at 8 weeks.
      RESULTS: Seventeen patients (34 refluxing ureters) underwent bilateral TVUR
      during the study period. They included 13 girls and 4 boys. The median age was
      4.6 years (range: 2-14 years). Two patients required conversion to open surgery.
      Resolution of VUR was seen in 16 patients (32 out of 34 ureters). Hydronephrosis
      resolved on postoperative ultrasonography in all patients with low-grade reflux
      (lower than grade IV) and all except one patient with grade IV reflux.
      CONCLUSION: TVUR is a feasible method with success rate equal to that of open
      technique if patient selection is good. Success rate is low in high-grade reflux,
      and dilated and tortuous ureter. Subtle modifications in the surgical steps can
      make significant contribution toward learning this minimally invasive technique.

PMID- 27890686
TI  - Cardiac and Skeletal Muscle Metastases From Squamous Cell Carcinoma of the
      Bladder: Positron Emission Tomography-Computed Tomography Findings.
AB  - We describe the positron emission tomography-computed tomography (PET-CT)
      findings of a patient who presented to the emergency room with chest pain and
      palpitations and underwent a radical cystectomy 6 months earlier because of a
      squamous cell carcinoma of the bladder (SCCB). Cardiac catheterization ruled out
      coronary artery occlusion, but PET-CT showed multiple F-18-fluorodeoxyglucose
      avid lesions involving multiple skeletal muscles and the heart, consistent with
      metastases. A CT-guided biopsy of 1 skeletal muscle lesion confirmed a metastasis
      with the same pathologic features as the SCCB. To our knowledge, this is the
      first reported case of an SCCB with metastases to multiple skeletal muscles and
      myocardium detected with PET-CT.

PMID- 27890687
TI  - Revisiting Sports Precautions in Children With Solitary Kidneys and Congenital
      Anomalies of the Kidney and Urinary Tract.
AB  - This review article explores sports and recreational precautions in children with
      solitary kidneys. In 2001, the American Academy of Pediatrics published
      recommendations for activity in children with medical conditions. Those with
      solitary kidneys were graded a "qualified yes": no restriction in noncontact
      sports, and individual assessment for limited-contact, contact, and collision
      sports. Recent trauma data suggest that classification according to the degree of
      contact is inaccurate. We propose an updated, data-driven classification of
      sports or recreation according to the risk of high-grade renal trauma or loss of
      renal unit. Given the paucity of literature on the topic and lack of consensus,
      children with congenital renal anomalies should exercise caution in both sports
      and recreation.

PMID- 27890688
TI  - Weight loss is associated with improvements in cognitive function among
      overweight and obese people: A systematic review and meta-analysis.
AB  - Whilst obesity is associated with a higher risk of cognitive impairment, the
      influence of weight loss on cognitive function in obese/overweight people is
      equivocal. We conducted a meta-analysis of randomized controlled trials (RCTs)
      and longitudinal studies evaluating the influence of voluntary weight loss on
      cognitive function in obese/overweight individuals. Articles were acquired from a
      systematic search of major databases from inception till 01/2016. A random effect
      meta-analysis of weight loss interventions (diet, physical activity, bariatric
      surgery) on different cognitive domains (memory, attention, executive functions,
      language and motor speed) was conducted. Twenty studies (13 longitudinal
      studies=551 participants; 7 RCTs=328 treated vs. 140 controls) were included.
      Weight loss was associated with a significant improvement in attention and memory
      in both longitudinal studies and RCTs, whereas executive function and language
      improved in longitudinal and RCT studies, respectively. In conclusion,
      intentional weight loss in obese/overweight people is associated with
      improvements in performance across various cognitive domains. Future adequately
      powered RCTs are required to confirm/refute these findings.

PMID- 27890690
TI  - Successful outcome with minimally invasive plate osteosynthesis for
      periprosthetic tibial fracture after total knee arthroplasty.
AB  - INTRODUCTION: The incidence of periprosthetic fractures after total knee
      arthroplasty (TKA) is increasing, and treatment is becoming more necessary. In
      periprosthetic tibial fractures, the stem of the tibial component largely
      occupies the medullary canal of the proximal tibia, which limits the selection of
      implants. The purpose of this study was to evaluate the effectiveness of the
      minimally invasive plate osteosynthesis (MIPO) technique with locking plates for
      periprosthetic tibial fractures after TKA. MATERIALS AND METHODS: Sixteen
      patients with periprosthetic tibial fracture after TKA were included. There were
      6 type II and 10 type III fractures according to the Felix classification. Ten
      patients had fractures in the proximal metaphysis, and 6 in the diaphysis. MIPO
      using locking plates was performed on the medial side in 4 cases, the lateral
      side in 2 cases, and both in 10 cases. Radiographic results included time to
      union, alignment, and malunion. Clinical results included range of motion (ROM),
      functional activity data, Knee Society scores, and complications. RESULTS:
      Fourteen of 16 fractures achieved union at 17.1 weeks (range, 14-24)
      postoperatively. There were 2 failures that required a secondary procedure.
      Except one for 1 case with varus malunion, all had acceptable alignment. Mean ROM
      at the final follow-up was 108.8 degrees  (range, 15-135 degrees ), and 15
      patients recovered pre-injury knee joint activity. Mean knee and function scores
      were 88.9 (range, 77-100) and 83.3 (range, 60-100), respectively. Knees with
      fewer than 8 cortices giving purchase to screws in the proximal segment showed
      higher failure rates (P=0.025). DISCUSSION: MIPO with locking plates can achieve
      satisfactory results for periprosthetic tibial fractures after TKA. Rigid
      fixation of the proximal segment may be necessary for successful outcome. LEVEL
      OF EVIDENCE: IV.

PMID- 27890691
TI  - Minimum four-year subsequent surgery rates of cervical disc replacement versus
      fusion: A meta-analysis of prospective randomized clinical trials.
AB  - INSTRUCTION: Anterior cervical discectomy and fusion (ACDF) is a well-accepted
      surgical management strategy for radiculopathy and/or myelopathy. However,
      complications sometimes required subsequent surgery at the operated and adjacent
      levels. Artificial cervical disc replacement (ACDR) has been accepted as the most
      extensive non-fusion procedure and is designed to preserve motion. However, some
      specific complications can result in subsequent surgery, thus, attracting the
      attention of investigators. HYPOTHESIS: Compared with ACDF, ACDR had a lower
      subsequent surgery rates at both operated and adjacent levels after a minimum of
      four-years of follow-up. MATERIAL AND METHODS: A meta-analysis was performed with
      articles published prior to February 2016. Only randomized controlled trials that
      reported a minimum of 4 years of follow-up with regard to the rates of subsequent
      surgeries after ACDR compared with ACDF were included in this study. Two
      reviewers independently screened the articles and data following the PRISMA
      statement. RESULTS: Our data showed that the pooled overall rate of subsequent
      surgery at the operated level and adjacent levels was lower in the ACDR group
      (7.4%) than in the ACDF group (16.8%) (P=0.0006). For subsequent surgery at the
      operated level, patients who received ACDR had a lower rate of subsequent surgery
      than patients who received ACDF (P<0.0001). With respect to the adjacent level,
      ACDR also had fewer subsequent surgeries compared with ACDF (P<0.0001).
      CONCLUSION: ACDR had significantly fewer subsequent surgical interventions
      compared with ACDF, However, a review of the literature showed that there were an
      insufficient number of studies with respect to subsequent surgery with a minimum
      of 4 years of follow-up. Hence, longer-term, multicenter studies are needed for
      better evaluation of the rate of subsequent surgery after ACDR. LEVEL OF
      EVIDENCE: Level I, meta-analysis of high-powered prospective randomized trials.

PMID- 27890692
TI  - Rapid identification of Robinsoniella peoriensis using specific 16S rRNA gene PCR
      primers.
AB  - Robinsoniella peoriensis is a Gram-positive, spore-forming anaerobic bacterium
      initially isolated and characterized from swine manure and feces. Since then
      strains of this species have been identified from a variety of mammalian and
      other GI tracts. More recently strains of this species have been isolated from a
      plethora of human infections. Therefore, it is of great interest to develop
      methods to rapidly identify this microorganism in the medical and other
      laboratories. This report describes the use of PCR primers targeting the 16S rRNA
      gene of R. peoriensis to identify strains of this bacterium.

PMID- 27890693
TI  - Developmental study of the Proboscis Extension Response to heat in Rhodnius
      prolixus along the life cycle.
AB  - Triatominae are blood-sucking insects that localise their hosts using a range of
      sensory signals to find food, and among them, the heat emitted by the hosts. Heat
      is one of the main short-range cues in vertebrate hosts, able to trigger alone
      the Proboscis Extension Response (PER) that precedes the bite. Previous studies
      demonstrated that heat responsiveness of fifth-instar nymphs is maximum to
      moderate temperatures (30-35 degrees C) compatible with those of their vertebrate
      host's body surface. This study investigated whether this thermal preference for
      biting is maintained along the life cycle of R. prolixus, from the first larval
      instar to male and female adults. The results showed that PER rates were at
      maximum around 30-35 degrees C and decreased for a warmer temperature. The same
      thermal preference was maintained all along the life cycle, despite the increase
      in the size of the antennae linked to the growth. Interestingly, a decreased
      thermal responsiveness was stated in males as compared with larval instars and
      females. This decrease might reveal a lower motivation for host-seeking and might
      have an impact on males's vectorial competence.

PMID- 27890694
TI  - Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first
      year of life.
AB  - Young infants are less susceptible to severe episodes of malaria but the targets
      and mechanisms of protection are not clear. Cord blood antibodies may play an
      important role in mediating protection but many studies have examined their
      association with the outcome of infection or non-severe malaria. Here, we
      investigated whether cord blood IgG to Plasmodium falciparum merozoite antigens
      and antibody-mediated effector functions were associated with reduced odds of
      developing severe malaria at different time points during the first year of life.
      We conducted a case-control study of well-defined severe falciparum malaria
      nested within a longitudinal birth cohort of Kenyan children. We measured cord
      blood total IgG levels against five recombinant merozoite antigens and antibody
      function in the growth inhibition activity and neutrophil antibody-dependent
      respiratory burst assays. We also assessed the decay of maternal antibodies
      during the first 6months of life. The mean antibody half-life range was
      2.51months (95% confidence interval (CI): 2.19-2.92) to 4.91months (95% CI: 4.47
      6.07). The rate of decline of maternal antibodies was inversely proportional to
      the starting concentration. The functional assay of antibody-dependent
      respiratory burst activity predicted significantly reduced odds of developing
      severe malaria during the first 6months of life (Odds ratio (OR) 0.07, 95% CI:
      0.007-0.74, P=0.007). Identification of the targets of antibodies mediating
      antibody-dependent respiratory burst activity could contribute to the development
      of malaria vaccines that protect against severe episodes of malaria in early
      infancy.

PMID- 27890695
TI  - Nitric oxide-polyamines cross-talk during dormancy release and germination of
      apple embryos.
AB  - Nitric oxide (NO) and polyamines (PAs) belong to plant growth and development
      regulators. These compounds play a key role in numerous physiological processes
      e.g. seed germination. Based on the suggestion of overlapping of NO and PAs
      biosynthetic pathways, we demonstrated a cross-talk of NO and PAs in regulation
      of embryonic dormancy release. The aim of the work was to investigate an impact
      of PAs (Put, Spd and Spm) or NO short-term fumigation on nitrite, urea, Arg and
      ornithine (Orn) content, NO synthase-like (NOS-like) and arginase activity in
      axes of apple (Malus domestica Borkh.) embryos during dormancy alleviation and at
      the stage of termination of germination sensu stricto. NO, Put/Spd induced
      dormancy breakage and germination of apple embryos corresponded to stimulation of
      urea cycle and high free Arg pool in seedlings roots. After two days of the
      culture Put and Spd stimulated Arg dependent NO formation, inhibition of which
      was observed after Spm application. Put or Spd application as well as NO short
      term pretreatment of apple embryos influenced level of ubiquitin-conjugated
      proteins. Higher abundance of such modified proteins correlated well to the
      declined content of nitrated proteins, suggesting their important role in
      regulation of embryo germination. NO led to stimulation of embryos germination by
      increasing level of free PAs (mostly Put). While transcriptomic approach showed
      down regulation of Spm synthesis and up-regulation of Spm degradation by NO,
      confirming negative role of Spm over-accumulation in embryo dormancy removal. Our
      data clearly indicate positive relationship of NO-Put/Spd acting as dormancy
      removing factors.

PMID- 27890689
TI  - Developmental toxicity of nicotine: A transdisciplinary synthesis and
      implications for emerging tobacco products.
AB  - While the health risks associated with adult cigarette smoking have been well
      described, effects of nicotine exposure during periods of developmental
      vulnerability are often overlooked. Using MEDLINE and PubMed literature searches,
      books, reports and expert opinion, a transdisciplinary group of scientists
      reviewed human and animal research on the health effects of exposure to nicotine
      during pregnancy and adolescence. A synthesis of this research supports that
      nicotine contributes critically to adverse effects of gestational tobacco
      exposure, including reduced pulmonary function, auditory processing defects,
      impaired infant cardiorespiratory function, and may contribute to cognitive and
      behavioral deficits in later life. Nicotine exposure during adolescence is
      associated with deficits in working memory, attention, and auditory processing,
      as well as increased impulsivity and anxiety. Finally, recent animal studies
      suggest that nicotine has a priming effect that increases addiction liability for
      other drugs. The evidence that nicotine adversely affects fetal and adolescent
      development is sufficient to warrant public health measures to protect pregnant
      women, children, and adolescents from nicotine exposure.

PMID- 27890697
TI  - A Stem Cell Donor for Every Adult Requiring an Allograft for Acute Lymphoblastic
      Leukemia?

PMID- 27890698
TI  - Clementine juice has the potential for drug interactions - In vitro comparison
      with grapefruit and mandarin juice.
AB  - Adverse drug interactions due to grapefruit juice are well known prompting
      warnings even in drug labels. Similar issues have not been reported for
      clementines and available data is scarce, despite of genetic descent. We observed
      substantially increased tacrolimus trough concentrations in a renal transplant
      patient consuming high clementine amounts and, thus, scrutinised the effects of
      clementine juice on drug metabolism and drug transporters in vitro and compared
      it to the effects of mandarin and grapefruit juice. All citrus juices profoundly
      induced several drug transporters and drug metabolising enzymes, whereas the
      effects of grapefruit juice were most pronounced (e.g. 156-fold and 34-fold
      induction of cytochrome P450 (CYP) 3A4 mRNA by grapefruit juice and clementine
      juice, respectively). However, the juices also inhibited e.g. CYP3A4, raising the
      question which effect prevails in vivo. Using an enzymatic activity assay, we
      demonstrated that at least in vitro CYP3A4 inhibition prevails for both
      grapefruit and clementine juice, whereas for CYP1A2 induction appears to
      predominate. Thus, inhibition of CYP3A4 is presumably the underlying reason for
      the observed increase in the concentrations of the CYP3A4 substrate tacrolimus in
      the patient. Taken together, our data indicate that clementine juice as well as
      grapefruit juice and to a lesser extent also mandarin juice can induce several
      important drug metabolising enzymes and drug transporters, but also inhibit some
      of these proteins. Our data indicate that clementine juice similar to grapefruit
      juice bears the potential for profound interactions with drugs potentially
      leading to adverse drug effects e.g. through over-exposure to CYP3A4 substrates.

PMID- 27890699
TI  - Ayurvedic management of spondyloepiphyseal dysplasia tarda, a rare hereditary
      disorder.
AB  - Spondyloepiphyseal dysplasia tarda (SEDT) is a rare genetic disease in which
      patient suffers from short stature, short trunk and neck with disproportionately
      long arms, coxa vara, skeletal features such as barrel shaped chest, kyphosis,
      scoliosis and early arthropathy. Only limited medical and surgical management is
      available in modern medicine. A 15 years old male suffering from SEDT and
      diagnosed as Vata vyadhi was treated with Panchakarma therapy and selected
      Ayurvedic oral medicines. Ayurvedic treatment was directed to ameliorate the
      orthopaedic clinical conditions in this case. Panchakarma procedures such as
      Shalishastika pinda svedana for a month and Mustadi yapana basti for 16 days were
      given along with oral Ayurvedic medicines. Same Panchakarma procedures were
      repeated after an interval of 2 months. A combination of Ayurvedic oral medicines
      such as Trayodashanga guggulu-500 mg twice a day, Dashmool kvatha (decoction of
      roots of 10 herbs) 40 ml twice a day, Eranda paka 10 g twice a day, Shiva gutika
      500 mg twice a day and Dashmoolarista-20 ml (with equal water) twice a day were
      prescribed. Eight scales based Medical outcome study (MOS) - 36 item short form -
      health surveys was assessed for outcome which shows good improvement. Kyphosis,
      scoliosis and pain were moderately reduced. Clinical experience of this case
      indicates that Ayurvedic herbs along with Panchakarma can play a major role in
      the management of hereditary disorder SEDT.

PMID- 27890696
TI  - Nitric oxide synthase and structure-based inhibitor design.
AB  - Once it was discovered that the enzyme nitric oxide synthase (NOS) is responsible
      for the biosynthesis of NO, NOS became a drug target. Particularly important is
      the over production of NO by neuronal NOS (nNOS) in various neurodegenerative
      disorders. After the various NOS isoforms were identified, inhibitor development
      proceeded rapidly. It soon became evident, however, that isoform selectivity
      presents a major challenge. All 3 human NOS isoforms, nNOS, eNOS (endothelial
      NOS), and iNOS (inducible NOS) have nearly identical active site structures thus
      making selective inhibitor design especially difficult. Of particular importance
      is the avoidance of inhibiting eNOS owing to its vital role in the cardiovascular
      system. This review summarizes some of the history of NOS inhibitor development
      and more recent advances in developing isoform selective inhibitors using
      primarily structure-based approaches.

PMID- 27890700
TI  - Biochanin-A attenuates neuropathic pain in diabetic rats.
AB  - BACKGROUND: Soya supplements are used in the treatment of neuropathic pain.
      Previous reports reveal that consumption of soy diet before nerve injury prevents
      the development of neuropathic pain in rats. Biochanin-A, a soy isoflavone, has a
      naturally occurring inhibitor of fatty acid amide hydrolase (FAAH) that
      metabolized endocannabinoids. OBJECTIVE: The objective was to evaluate efficacy
      of biochanin-A in streptozotocin (STZ) induced neuropathic pain in rat model.
      MATERIALS AND METHODS: Diabetes mellitus was induced by an injection of STZ at a
      dose of 45 mg/kg, i.v. into tail vein of male albino Wistar rats. Biochanin-A was
      dosed at 0.1, 1 and 5 mg/kg by intraperitoneal (i.p.) administration in diabetic
      neuropathic rats. Mechanical hyperalgesia and allodynia was measured using
      Randall-Selitto analgesymeter and manual von Frey filaments of increasing weights
      respectively. Paw withdrawal threshold (PWT) and percent PWT was determined with
      respect to both hyperalgesia and allodynia. RESULTS: Treatment of biochanin-A at
      three different levels of 0.1, 1 and 5 mg/kg had not significantly altered serum
      glucose levels throughout the treatment period. In hyperalgesia study, acute
      treatment with higher dose exhibited 51.1% reversal of paw withdrawal threshold
      (PWT) while with chronic treatment, efficacy declined to 22.5% reversal of PWT.
      In allodynia study, acute treatment reversed PWT by 79.4% while with chronic
      treatment, efficacy was raised to 88.2% reversal of PWT. CONCLUSION: Biochanin-A
      demonstrated better efficacy in reversing mechanical allodynia than mechanical
      hyperalgesia. Biochanin-A could be a good drug candidate for further studies to
      establish the mechanism of attenuation of neuropathic pain.

PMID- 27890701
TI  - Evaluation for substitution of stem bark with small branches of Myrica esculenta
      for medicinal use - A comparative phytochemical study.
AB  - BACKGROUND: Over exploitation of many traditional medicinal plants like Myrica
      esculenta has become a threat and in the near future, many medicinal plants may
      be unavailable for use of industry. OBJECTIVE: Present study outlines the concept
      of plant part substitution. Stem bark and small branches of M. esculenta are
      compared on the basis of physicochemical analysis, phytochemical analysis, total
      phenolic contents, total flavonoid contents and high performance thin layer
      chromatography (HPTLC) to evaluate the possibilities of using small branches in
      place of stem bark. MATERIAL AND METHODS: Physicochemical parameters and
      preliminary phytochemical screening were carried out using standard methods.
      Total phenolic and total flavonoid contents were estimated spectrophotometrically
      using Folin-Ciocalteu and aluminum chloride method, respectively. CAMAG HPTLC
      system equipped with semi-automatic applicator was used for HPTLC profiling. n
      Hexane, ethyl acetate and ethanol extracts of stem bark and small branches were
      developed in suitable mobile phase using standard procedures and visualized in UV
      254 and 366 nm and in white light after derivatization within anisaldehyde
      sulphuric acid reagent. RESULTS: Phytochemical analysis and HPTLC profile of
      different extracts showed the presence of almost similar phytochemicals in both
      stem bark and small branches. CONCLUSION: Similarities in phytochemical analysis
      and HPTLC profile of various extracts suggests that small branches may be used in
      place of stem bark. The study provides the base for further study to use small
      branches as a substitute of stem bark of M. esculenta.

PMID- 27890702
TI  - FOXOs in the impaired heart: New therapeutic targets for cardiac diseases.
AB  - Cardiac diseases have a high morbidity and mortality and affect the global
      population. Based on recent accumulating evidence, Forkhead box O (FOXOs) play
      important roles in cardiac diseases. Therefore, a summary of the current
      literature on the molecular mechanisms and roles of FOXOs in the heart will
      provide valuable information. In this review, we first briefly introduce the
      molecular features of FOXOs. Then, we discuss the regulation and cardiac actions
      of the FOXO pathways. Based on this background, we expand our discussion to the
      roles of FOXOs in several major cardiac diseases, such as ischemic cardiac
      diseases, diabetic cardiomyopathy and myocardial hypertrophy. Then, we describe
      some methodological problems associated with the FOXO gene-modified animal
      models. Finally, we discuss potential future directions. The information reviewed
      here may be significant for the design of future studies and may increase the
      potential of FOXOs as therapeutic targets.

PMID- 27890703
TI  - Vitamin B6 metabolism in microbes and approaches for fermentative production.
AB  - Vitamin B6 is a designation for the six vitamers pyridoxal, pyridoxine,
      pyridoxamine, pyridoxal 5'-phosphate (PLP), pyridoxine 5'-phosphate, and
      pyridoxamine. PLP, being the most important B6 vitamer, serves as a cofactor for
      many proteins and enzymes. In contrast to other organisms, animals and humans
      have to ingest vitamin B6 with their food. Several disorders are associated with
      vitamin B6 deficiency. Moreover, pharmaceuticals interfere with metabolism of the
      cofactor, which also results in vitamin B6 deficiency. Therefore, vitamin B6 is a
      valuable compound for the pharmaceutical and the food industry. Although vitamin
      B6 is currently chemically synthesized, there is considerable interest on the
      industrial side to shift from chemical processes to sustainable fermentation
      technologies. Here, we review recent findings regarding biosynthesis and
      homeostasis of vitamin B6 and describe the approaches that have been made in the
      past to develop microbial production processes. Moreover, we will describe novel
      routes for vitamin B6 biosynthesis and discuss their potential for engineering
      bacteria that overproduce the commercially valuable substance. We also highlight
      bottlenecks of the vitamin B6 biosynthetic pathways and propose strategies to
      circumvent these limitations.

PMID- 27890704
TI  - Cryopreservation of adult cervid testes.
AB  - Several species of cervids are currently classified as threatened or endangered
      due to a rapid decline in their populations. Sperm cryopreservation, in
      association with assisted reproductive technologies, can find application for the
      conservation of endangered cervids. In cases of unsuccessful sperm retrieval
      through other means prior to the death of the animal, adult testis is the only
      source of sperm. Recovery of viable sperm from adult testes depends on the
      effective preservation of testicular tissues through optimization of
      cryopreservation protocols. The present study evaluated combinations of 10%
      dimethyl sulfoxide (DMSO) with 0% or 80% fetal bovine serum (FBS) and 20% DMSO
      with 0 or 20% FBS for the cryopreservation of testicular tissues of three adult
      cervids using uncontrolled slow freezing protocol. The cryopreserved testis was
      compared to chilled tissue without cryoprotectants. Results revealed that
      testicular tissues of barking deer cryopreserved in 20% DMSO (D20) had all the
      analyzed 7 parameters (number of TNP1-, PRM2 and acrosin-expressing cells/tubule
      and, the number of viable, morphologically normal, acrosome intact, Annexin V
      negative sperm) comparable to the chilled testis. However, testicular tissues of
      sambhar and hog deer cryopreserved only in D20S20 had 5 of 7 parameters
      comparable to the chilled testis. In conclusion, D20 is acceptable for
      cryopreservation of barking deer and D20S20 for sambar and hog deer testes.

PMID- 27890705
TI  - Selective rehearsal is affected by the emotionality of the encoding context in
      item-method directed forgetting: An event-related potential study.
AB  - Emotional items are often remembered more clearly than neutral items. However,
      whether stimuli embedded in an emotional context are more resistant to directed
      forgetting than those presented in a neutral context remains unclear. This
      question was tested by recording event-related potentials (ERPs) in an item
      method directed forgetting paradigm involving neutral words that were embedded in
      neutral or negative contexts. During the study phase, participants were asked to
      associate a neutral word with a negative or neutral picture. A remember (R) or
      forget (F) cue was then designated to indicate whether the word was a to-be
      remembered (TBR) or to-be-forgotten (TBF) word. In the test phase, participants
      were asked to identify all previously presented old words regardless of the R/F
      cues. The behavioral results indicated a significant interaction between the
      valence of the encoding contexts and the R/F cues. The hit rate was lower for the
      TBR words encoded in negative contexts relative to those encoded in neutral
      contexts. No such valence effect was observed in the hit rates of the TBF words.
      For the ERP data, the R cues elicited a P3b-like effect that has been linked to
      the selective rehearsal of the TBR items. This effect was more sustained in the
      negative encoding context than in the neutral context. The F cues elicited a
      frontal positivity that has been linked to the active inhibition of the TBF
      words; however, this positivity was not modulated by the valence of the encoding
      context. The sustained P3b-like effect for the R cues in the negative encoding
      context might reflect a compensative encoding for the TBR words caused by the
      attention-capturing negative contexts. Therefore, we argue that the emotional
      context affected the selective elaboration of the TBR words; however, we also
      argue that there was no supportive evidence of an emotional effect on the
      forgetting of TBF items.

PMID- 27890706
TI  - The sphingosine-1-phosphate receptor: A novel therapeutic target for multiple
      sclerosis and other autoimmune diseases.
AB  - Multiple sclerosis (MS) is a prototype autoimmune disease of the central nervous
      system (CNS). Currently, there is no drug that provides a cure for MS. To date,
      all immunotherapeutic drugs target relapsing remitting MS (RR-MS); it remains a
      daunting medical challenge in MS to develop therapy for secondary progressive MS
      (SP-MS). Since the approval of the non-selective sphingosine-1-phosphate (S1P)
      receptor modulator FTY720 (fingolimod [Gilenya(r)]) for RR-MS in 2010, there have
      been many emerging studies with various selective S1P receptor modulators in
      other autoimmune conditions. In this article, we will review how S1P receptor may
      be a promising therapeutic target for SP-MS and other autoimmune diseases such as
      psoriasis, polymyositis and lupus.

PMID- 27890707
TI  - Novel mutation in DOCK8-HIES with severe phenotype and successful
      transplantation.
AB  - BACKGROUND: Hyper-IgE syndrome (HIES) due to DOCK8 deficiency is an autosomal
      recessive (AR) primary combined immunodeficiency which results in significant
      morbidity and mortality at a young age. Different mutations in the DOCK8 gene can
      lead to variable severity of the disease. OBJECTIVE: We evaluated the genetic
      mutations in three related patients with severe clinical manifestations
      suggestive of AR HIES. We also explored whether treatment with stem cell
      transplantation could lead to complete disease resolution. METHOD: We examined
      the clinical manifestations and immunological workup of these patients. Their DNA
      was also screened for causative mutation. Post transplantation, clinical and
      immunological data for the transplanted patient was also collected. RESULTS: All
      patients had a severe course of the disease with rarely reported severe
      complications in HIES. One patient died with lymphoma while another died with
      progressive multifocal leukoencephalopathy (PML) due to a slow virus. All our
      patients had two novel mutations in the DOCK8 gene. One of these mutations was a
      novel pathogenic mutation and explains the severity of the disease (homozygous
      splice site mutation at position 5 after the end of exon 45), while the other
      mutation was mostly non-pathogenic. Hematopoietic stem cell transplantation
      (HSCT) was performed in the youngest patient with excellent engraftment and full
      reversibility of the clinical manifestations. CONCLUSION: We report 3 patients
      from a consanguineous family diagnosed with AR-HIES due to a novel pathogenic
      mutation in DOCK8 gene leading to fatal outcome in 2 patients and complete
      resolution of the clinical and immunological features in the third patient by
      HSCT.

PMID- 27890708
TI  - Fbxl18 targets LRRK2 for proteasomal degradation and attenuates cell toxicity.
AB  - Dominantly inherited mutations in leucine-rich repeat kinase 2 (LRRK2) are the
      most common causes of familial Parkinson's disease (PD) and LRRK2 polymorphisms
      are associated with increased risk for idiopathic PD. However, the molecular
      mechanisms by which these mutations cause PD remain uncertain. In vitro studies
      indicate that disease-linked mutations in LRRK2 increase LRRK2 kinase activity
      and LRRK2-mediated cell toxicity. Identifying LRRK2-interacting proteins and
      determining their effects on LRRK2 are important for understanding LRRK2 function
      and for delineating the pathophysiological mechanisms of LRRK2 mutations. Here we
      identified a novel protein, F-box and leucine-rich repeat domain-containing
      protein 18 (Fbxl18) that physically associates with LRRK2. We demonstrated that
      Fbxl18 is a component of a Skp1-Cullin1-F-box ubiquitin ligase complex that
      regulates the abundance of LRRK2 by selectively targeting phosphorylated LRRK2
      for ubiquitination and proteasomal degradation. Knockdown of endogenous Fbxl18
      stabilized LRRK2 abundance while protein kinase C activation enhanced LRRK2
      degradation by Fbxl18. Dephosphorylation of LRRK2 blocked Fbxl18 association with
      LRRK2. Taken together, we have identified potential mechanisms for LRRK2
      regulation by kinase signaling pathways. Furthermore, Fbxl18 prevented caspase
      activation and cell death caused by LRRK2 and PD-linked mutant LRRK2. This
      reveals novel targets for developing potential therapies for familial and
      idiopathic PD.

PMID- 27890710
TI  - In vivo and vitro characterization of the effects of kisspeptin-13, endogenous
      ligands for GPR54, on mouse gastrointestinal motility.
AB  - Kisspeptin (KP), the endogenous ligand of GPR54, is a mammalian amidated
      neurohormone, which belongs to the RF-amide peptide family. However, in contrast
      with the related members of the RF-amide family, little information is available
      regarding its role in the gastrointestinal motility. With regard to the recent
      data suggesting KP play an important role in food intake, and while
      gastrointestinal motility are closely related to it. Thus, in the present work,
      effects of central administration of KP-13, one of the endogenous active
      isoforms, on gastrointestinal motility were investigated. The results indicated
      that intracerebroventricular (i.c.v.) infused of KP-13 significantly facilitated
      gastrointestinal transit, bead expulsion and fecal pellet output, respectively,
      while has no effect on gastric emptying. The effects were significantly reversed
      by GPR54 antagonist 234, but not GnRH receptor antagonist Cetrorelix. However,
      i.p. injected of KP-13 or compound 5 (10mg/kg), a high metabolic stability
      kisspeptin analog, did not affect gastrointestinal transit, suggesting that KP-13
      or compound 5 facilitated gastrointestinal transit through the activation of
      central GPR54. Then the gastrointestinal motility-enhancing effects were also
      presented after infusion of KP-13 into the hypothalamus. In vitro, KP-13 (10-6M)
      also modulated colonic contraction, but not in the stomach and small intestine.
      Similarly, KP-13 (10-6M)-induced contractions of circular and longitudinal
      colonic muscle were significantly attenuated by antagonist 234 (10-6M). In
      conclusion, all the results indicated that KP-13 promoted gastrointestinal
      motility through the activation of GPR54, which implicate that KP/GPR54 system
      might be a new target to treat gastrointestinal function disorder.

PMID- 27890709
TI  - Role of major and brain-specific Sgce isoforms in the pathogenesis of myoclonus
      dystonia syndrome.
AB  - Loss-of-function mutations in SGCE, which encodes epsilon-sarcoglycan (epsilon
      SG), cause myoclonus-dystonia syndrome (OMIM159900, DYT11). A "major" epsilon-SG
      protein derived from CCDS5637.1 (NM_003919.2) and a "brain-specific" protein,
      that includes sequence derived from alternative exon 11b (CCDS47642.1,
      NM_001099400.1), are reportedly localized in post- and pre-synaptic membrane
      fractions, respectively. Moreover, deficiency of the "brain-specific" isoform and
      other isoforms derived from exon 11b may be central to the pathogenesis of DYT11.
      However, no animal model supports this hypothesis. Gene-trapped ES cells (CMHD
      GT_148G1-3, intron 9 of NM_011360) were used to generate a novel Sgce mouse model
      (C57BL/6J background) with markedly reduced expression of isoforms derived from
      exons 3' to exon 9 of NM_011360. Among those brain regions analyzed in adult
      (2month-old) wild-type (WT) mice, cerebellum showed the highest relative
      expression of isoforms incorporating exon 11b. Homozygotes
      (SgceGt(148G1)Cmhd/Gt(148G1)Cmhd or SgceGt/Gt) and paternal heterozygotes
      (Sgcem+/pGt, m-maternal, p-paternal) showed 60 to 70% reductions in expression of
      total Sgce. Although expression of the major (NM_011360) and brain-specific
      (NM_001130189) isoforms was markedly reduced, expression of short isoforms was
      preserved and relatively small amounts of chimeric epsilon-SG/beta-galactosidase
      fusion protein was produced by the Sgce gene-trap locus. Immunoaffinity
      purification followed by mass spectrometry assessments of Sgcem+/pGt mouse brain
      using pan- or brain-specific epsilon-SG antibodies revealed significant
      reductions of epsilon-SG and other interacting sarcoglycans. Genome-wide gene
      expression data using RNA derived from adult Sgcem+/pGt mouse cerebellum showed
      that the top up-regulated genes were involved in cell cycle, cellular
      development, cell death and survival, while the top down-regulated genes were
      associated with protein synthesis, cellular development, and cell death and
      survival. In comparison to WT littermates, Sgcem+/pGt mice exhibited "tiptoe"
      gait and stimulus-induced appendicular posturing between Postnatal Days 14 to 16.
      Abnormalities noted in older Sgcem+/pGt mice included reduced body weight,
      altered gait dynamics, and reduced open-field activity. Overt spontaneous or
      stimulus-sensitive myoclonus was not apparent on the C57BL/6J background or mixed
      C57BL/6J-BALB/c and C57BL/6J-129S2 backgrounds. Our data confirm that mouse Sgce
      is a maternally imprinted gene and suggests that short Sgce isoforms may
      compensate, in part, for deficiency of major and brain-specific Sgce isoforms.

PMID- 27890711
TI  - The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP
      dependent vasorelaxant.
AB  - N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G
      protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance
      arteries. This study investigates its hemodynamic effects and mechanisms of
      vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac
      system and its vascular responses were assessed using a wire myograph. NAGLY
      (1mg/kg) decreased blood pressure by 69.4+/-5.5% and reduced renal blood flow by
      88+/-12% and the effects were not sensitive to inhibition by O-1918 (3mg/kg). In
      resistant vessels, NAGLY (1-30uM) induced concentration- and endothelium
      dependent vasorelaxation and the effect was inhibited by the nitric oxide
      synthase inhibitor, L-NAME (300uM), a cGMP synthase inhibitor, ODQ (10uM), the
      antagonists of "endothelial anandamide" receptor, rimonabant (3uM) and O-1918
      (10uM) and the inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943 (10uM). On the
      other hand, NAGLY-induced vasorelaxation was not affected by CID 16020046 (GPR55
      antagonist), AM 251 (cannabinoid CB1 receptor antagonist), AM 630 (cannabinoid
      CB2 receptor antagonist), capsazepine (TRPV1 antagonist), indomethacin
      (cyclooxygenase inhibitor), TRAM34 (IKCa channel blocker), iberiotoxin (BKCa
      channel blocker) and GW9662 (PPAR? antagonist). At low concentrations of
      carbachol, NAGLY potentiated carbachol-induced vasorelaxation. NAGLY is an
      endothelium-dependent vasodilator and hypotensive lipid. The vasorelaxation is
      predominantly via activation of nitric oxide-cGMP pathway and NCX and probably
      mediated by the "endothelial anandamide" receptor, while the hypotensive effect
      of NAGLY appears not to involve the anandamide receptor. NAGLY also potentiates
      carbachol-induced vasorelaxation, the mechanism of which might involve
      stimulation of NO release.

PMID- 27890712
TI  - Quantitative CT Measures of Bronchiectasis in Smokers.
AB  - BACKGROUND: Bronchiectasis is frequent in smokers with COPD; however, there are
      only limited data on objective assessments of this process. The objective was to
      assess bronchovascular morphology, calculate the ratio of the diameters of
      bronchial lumen and adjacent artery (BA ratio), and identify those measurements
      able to discriminate bronchiectasis. METHODS: We collected quantitative CT (QCT)
      measures of BA ratios, peak wall attenuation, wall thickness (WT), wall area, and
      wall area percent (WA%) at matched fourth through sixth airway generations in 21
      ever smokers with bronchiectasis (cases) and 21 never-smoking control patients
      (control airways). In cases, measurements were collected at both bronchiectatic
      and nonbronchiectatic airways. Logistic analysis and the area under receiver
      operating characteristic curve (AUC) were used to assess the predictive ability
      of QCT measurements for bronchiectasis. RESULTS: The whole-lung and fourth
      through sixth airway generation BA ratio, WT, and WA% were significantly greater
      in bronchiectasis cases than control patients. The AUCs for the BA ratio to
      predict bronchiectasis ranged from 0.90 (whole lung) to 0.79 (fourth-generation).
      AUCs for WT and WA% ranged from 0.72 to 0.75 and from 0.71 to 0.75. The artery
      diameters but not bronchial diameters were smaller in bronchiectatic than both
      nonbronchiectatic and control airways (P < .01 for both). CONCLUSIONS: Smoking
      related increases in the BA ratio appear to be driven by reductions in vascular
      caliber. QCT measures of BA ratio, WT, and WA% may be useful to objectively
      identify and quantify bronchiectasis in smokers. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

PMID- 27890713
TI  - Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary
      Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial.
AB  - BACKGROUND: Despite Food and Drug Administration approval of 2 new drugs for
      idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and
      mortality remains high. Preclinical and clinical data support the safety of human
      mesenchymal stem cells as a potential novel therapy for this fatal condition. The
      Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via
      Intravenous Delivery (AETHER) trial was the first study designed to evaluate the
      safety of a single infusion of bone marrow-derived mesenchymal stem cells in
      patients with idiopathic pulmonary fibrosis. METHODS: Nine patients with mild to
      moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single
      IV infusion of 20, 100, or 200 * 106 human bone marrow-derived mesenchymal stem
      cells per infusion from young, unrelated, men. All baseline patient data were
      reviewed by a multidisciplinary study team to ensure accurate diagnosis. The
      primary end point was the incidence (at week 4 postinfusion) of treatment
      emergent serious adverse events, defined as the composite of death, nonfatal
      pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically
      significant laboratory test abnormalities. Safety was assessed until week 60 and
      additionally 28 days thereafter. Secondary efficacy end points were exploratory
      and measured disease progression. RESULTS: No treatment-emergent serious adverse
      events were reported. Two nontreatment-related deaths occurred because of
      progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks
      postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean
      decline in % predicted diffusing capacity of the lungs for carbon monoxide.
      CONCLUSIONS: Data from this trial support the safety of a single infusion of
      human mesenchymal stem cells in patients with mild-moderate IPF. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.

PMID- 27890715
TI  - Effects of atrazine on ovarian growth, in the estuarine crab Neohelice granulata.
AB  - Atrazine, a herbicide that is intensively used in Argentina, was assayed to
      evaluate the alteration of reproduction in a wild species of crustaceans. Adult
      females of the estuarine crab Neohelice granulata were exposed to formulated
      atrazine during the 3-month pre-reproductive period. Three atrazine
      concentrations (0.03, 0.3 and 3mg/L) were assayed, together with a water dilution
      control. At the end of the exposure period, several variables concerning the
      energetic status of animals were measured, such as weight gain, glycemia, and
      energy reserves in both muscle and hepatopancreas. The gonadosomatic index (GSI)
      was also determined, as well as the proportion and relative area of each oocyte
      type in histological sections. Besides, the total content of vitellogenin
      proteins (Vg) in both ovary and hepatopancreas was measured. A significant
      (p<0.05) decrease of glycogen content was observed in muscle, while a significant
      (p<0.05) lower area of both previtellogenic and vitellogenic oocytes was verified
      in the ovary by effect of atrazine, in correspondence with a Vg content
      significantly (p<0.05) diminished in the ovary and augmented in the
      hepatopancreas. Besides, a higher proportion of previtellogenic oocytes were seen
      by effect of atrazine. Taken together, these results indicate a clear reduction
      and delay in the ovarian growth of the studied species, during the period at
      which the ovary normally grows up prior to spawning. On the other hand, a
      decrease of Vg content was observed at 0.3 and 3mg/L of atrazine after 24-h in
      vitro assays carried out with ovarian explants, providing additional evidence
      about the inhibitory role of this herbicide on the ovarian growth. These results
      encourage future research on deleterious effects of atrazine on crustacean
      reproduction.

PMID- 27890714
TI  - A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the
      Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial.
AB  - BACKGROUND: Clinical failures in ventilator-associated pneumonia (VAP) caused by
      gram-negative bacteria are common and associated with substantial morbidity,
      mortality, and resource utilization. METHODS: We assessed the safety and efficacy
      of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram
      negative bacterial VAP in a randomized double-blind, placebo-controlled, parallel
      group, phase 2 study between May 2013 and March 2016. We compared standard of
      care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline),
      delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via
      the investigational eFlow Inline System (PARI GmbH). The primary efficacy end
      point was change from baseline in the Clinical Pulmonary Infection Score (CPIS)
      during the randomized course of AFIS/placebo, using the subset of patients with
      microbiologically proven baseline infections with gram-negative bacteria.
      RESULTS: There were 143 patients randomized: 71 to the AFIS group, and 72 to the
      placebo group. Comparison of CPIS change from baseline between treatment groups
      was not different (P = .70). The secondary hierarchical end point of no mortality
      and clinical cure at day 14 or earlier was also not significant (P = .68) nor was
      the hierarchical end point of no mortality and ventilator-free days (P = .06).
      The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo
      group (P = .32). The AFIS group had significantly fewer positive tracheal
      cultures on days 3 and 7 than placebo. CONCLUSIONS: In this trial of adjunctive
      aerosol therapy compared with standard of care IV antibiotics in patients with
      gram-negative VAP, the AFIS was ineffective in improving clinical outcomes
      despite reducing bacterial burden. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01969799; URL: www.clinicaltrials.gov.

PMID- 27890716
TI  - A field study of hemolymph yolk protein levels in a bivalve (Unio tumidus) and
      future considerations for bivalve yolk protein as endocrine biomarker.
AB  - Induction of yolk protein in male fish is a recognized biomarker for estrogenic
      exposure because the estrogen-dependent induction mechanism is well investigated
      and there is a clear difference in yolk protein levels of unexposed males and
      females. Attempts have been made to use induction of bivalve yolk protein as
      biomarker for estrogenic exposure. However, several biomarker validation criteria
      have not yet been investigated e.g. an in-depth understanding of the induction
      mechanism and background variability is needed and reliable detection assays are
      yet to be developed. To obtain background knowledge about yolk protein levels
      freshwater bivalves (Unio tumidus) were collected in an uncontaminated Danish
      lake over the course of a year (33 collection dates). The hemolymph yolk protein
      concentration of 569 individuals was determined by a species specific enzyme
      linked immunosorbent assay (ELISA) and male and female gonadal development cycles
      were established. The average yolk protein levels of males and females collected
      at each sampling date overlapped in some periods; the male and female range was
      66,946 - 169,692 ng/mL and 88,731 - 681,667 ng/mL, respectively. Because male and
      female hemolymph yolk protein levels overlap, great care should be taken if yolk
      protein induction in bivalve hemolymph is considered as endocrine biomarker.

PMID- 27890717
TI  - Ecdysone receptor (EcR) and ultraspiracle (USP) genes from the cyclopoid copepod
      Paracyclopina nana: Identification and expression in response to water
      accommodated fractions (WAFs).
AB  - Ecdysteroid hormones are pivotal in the development, growth, and molting of
      arthropods, and the hormone pathway is triggered by binding ecdysteroid to a
      heterodimer of the two nuclear receptors; ecdysone receptors (EcR) and
      ultraspiracle (USP). We have characterized EcR and USP genes, and their 5'
      untranslated region (5'-UTR) from the copepod Paracyclopina nana, and studied
      mRNA transcription levels in post-embryonic stages and in response to water
      accommodated fractions (WAFs) of crude oil. The open reading frames (ORF) of EcR
      and USP were 1470 and 1287bp that encoded 490 and 429 amino acids with molecular
      weight of 121.18 and 105.03kDa, respectively. Also, a well conserved DNA-binding
      domain (DBD) and ligand-binding domain (LBD) were identified which confirmed by
      phylogenetic analysis. Messenger RNA transcriptional levels of EcR and USP were
      developmental stage-specific in early post-embryonic stages (N3-4). However, an
      evoked expression of USP was observed throughout copepodid stage and in adult
      females. WAFs (40 and 80%) were acted as an ecdysone agonist in P. nana, and
      elicited the mRNA transcription levels in adults. Developmental stage-specific
      transcriptional activation of EcR and USP in response to WAFs was observed. USP
      gene was down-regulated in the nauplius in response to WAF, whereas up-regulation
      of USP was observed in the adults. This study represents the first data of
      molecular elucidation of EcR and USP genes and their regulatory elements from P.
      nana and the developmental stage specific expression in response to WAFs, which
      can be used as potential biomarkers for environmental stressors with
      ecotoxicological evaluations in copepods.

PMID- 27890718
TI  - Thalassaemia screening and confirmation of carriers in parents.
AB  - Haemoglobinopathies are among the most common inherited monogenic disorders
      worldwide. Thalassaemia screening for carrier status is recommended for adults of
      reproductive age if suspected of being at risk. Conventional laboratory methods
      for screening include the assessment of haematological indices, and high
      performance liquid chromatography, capillary electrophoresis or isoelectric
      focusing to measure the levels of HbA2 and HbF, and to identify haemoglobin
      variants. Each screening method has its advantages and disadvantages, the main
      disadvantage being that none can fully resolve all variants. The complex nature
      of the genetics of haemoglobinopathies necessitates expertise in the
      interpretation of screening results to evaluate the most likely genotypes, which
      must then be confirmed using the DNA diagnosis. This review highlights the limits
      and pitfalls of each screening technique, and outlines a rational combination of
      different methods to overcome issues in thalassaemia carrier detection.

PMID- 27890719
TI  - Casting a smaller net into a bigger donor pool: A single center's experience with
      the new kidney allocation system.
AB  - The new kidney allocation system (KAS) provides additional allocation points for
      candidates with broad HLA sensitization in an effort to increase transplant rates
      for this underserved population. Following the implementation of KAS, our center
      lowered the HLA antibody threshold for listing unacceptable antigens from a
      cytotoxicity crossmatch level to a flow cytometric crossmatch level increasing
      Calculated Panel Reactive Antibody (CPRA) values and allocation points, yet
      restricting acceptable donor HLA phenotypes. As a result, many sensitized
      candidates were transitioned from 50% to 98% CPRA categories into the 99% CPRA
      regional share and 100% CPRA national share categories. Exposure to these larger
      donor pools significantly increased transplantation with compatible donors for
      100% CPRA candidates, but regional sharing was not sufficient to increase
      transplantation rates for our 99% CPRA candidates. Competition within the 100%
      CPRA cohort identified inequities for 99.99-100.0% CPRA candidates and
      highlighted the continued need for desensitization therapies to reduce
      immunological barriers and provide transplant opportunities for the most highly
      sensitized candidates.

PMID- 27890720
TI  - The Lawa model: A sustainable, integrated opisthorchiasis control program using
      the EcoHealth approach in the Lawa Lake region of Thailand.
AB  - Opisthorchiasis caused by the carcinogenic liver fluke Opisthorchis viverrini is
      a major foodborne parasitic zoonotic disease in Thailand and neighboring Mekong
      countries. The infection is associated with several hepatobiliary diseases
      including cholangiocarcinoma (CCA). The rates of CCA in regions where the
      parasite is endemic are unprecedented. Extensive research on various aspects of
      opisthorchiasis has been conducted in recent decades. However, the current status
      of O. viverrini infection in the country is approaching 85% prevalence in certain
      endemic areas even after more than 30years of control programs in Thailand. The
      complex life cycle of the fluke, which involves several hosts/environments, makes
      it difficult to control by conventional methods. Therefore, a new control
      strategy using the EcoHealth/One Health approach named the "Lawa model" was
      introduced into the liver fluke endemic Lawa Lake region in Khon Kaen Province.
      This program has been underway for over ten years. The program includes treatment
      with anthelmintic drugs, novel intensive health education methods both in the
      communities and in schools, ecosystem monitoring and active community
      participation. We developed the "Liver fluke-free school program" as a part of
      the Lawa model with successful results. All key stakeholders were empowered to
      obtain competency in their control activities for the sustainability of the
      program in the community. Nowadays, the infection rate in the 12 villages
      surrounding the lake has declined to less than 10% from an average of 60% at the
      start. The Cyprinid fish species now show less than 1% prevalence of infection
      compared with a maximum of 70% during the baseline survey. No infected Bithynia
      snails in the lake were found during recent field studies. Of the lessons learned
      from the Lawa model, the importance of community participation is one practical
      and essential component. The key to the success of the project is multi
      stakeholder participation with the active local Health Promoting Hospitals and
      the village health volunteers. The idea of the Lawa model is on the national
      agenda against liver fluke infection and CCA and is being scaled up to work in
      larger areas in Thailand. Internationally, the "Lawa model" is one of two
      programs that are showcased as successful control programs for helminths by the
      WHO Neglected Zoonotic Diseases (NZD4). Several media outlets have broadcast news
      reports about the program.

PMID- 27890721
TI  - Reactive gamma-ketoaldehydes as novel activators of hepatic stellate cells in
      vitro.
AB  - AIMS: Products of lipid oxidation, such as 4-hydroxynonenal (4-HNE), are key
      activators of hepatic stellate cells (HSC) to a pro-fibrogenic phenotype.
      Isolevuglandins (IsoLG) are a family of acyclic gamma-ketoaldehydes formed
      through oxidation of arachidonic acid or as by-products of the cyclooxygenase
      pathway. IsoLGs are highly reactive aldehydes which are efficient at forming
      protein adducts and cross-links at concentrations 100-fold lower than 4
      hydroxynonenal. Since the contribution of IsoLGs to liver injury has not been
      studied, we synthesized 15-E2-IsoLG and used it to investigate whether IsoLG
      could induce activation of HSC. RESULTS: Primary human HSC were exposed to 15-E2
      IsoLG for up to 48h. Exposure to 5MUM 15-E2-IsoLG in HSCs promoted cytotoxicity
      and apoptosis. At non-cytotoxic doses (50 pM-500nM) 15-E2-IsoLG promoted HSC
      activation, indicated by increased expression of alpha-SMA, sustained activation
      of ERK and JNK signaling pathways, and increased mRNA and/or protein expression
      of cytokines and chemokines, which was blocked by inhibitors of JNK and NF-kB. In
      addition, IsoLG promoted formation of reactive oxygen species, and induced an
      early activation of ER stress, followed by autophagy. Inhibition of autophagy
      partially reduced the pro-inflammatory effects of IsoLG, suggesting that it might
      serve as a cytoprotective response. INNOVATION: This study is the first to
      describe the biological effects of IsoLG in primary HSC, the main drivers of
      hepatic fibrosis. CONCLUSIONS: IsoLGs represent a newly identified class of
      activators of HSC in vitro, which are biologically active at concentrations as
      low as 500 pM, and are particularly effective at promoting a pro-inflammatory
      response and autophagy.

PMID- 27890723
TI  - Global gene expression changes in the prefrontal cortex of rabbits with
      hypercholesterolemia and/or hypertension.
AB  - Although many studies have identified a link between hypercholesterolemia or
      hypertension and cognitive deficits, till date, comprehensive gene expression
      analyses of the brain under these conditions is still lacking. The present study
      was carried out to elucidate differential gene expression changes in the
      prefrontal cortex (PFC) of New Zealand white rabbits exposed to
      hypercholesterolemia and/or hypertension with a view of identifying gene networks
      at risk. Microarray analyses of the PFC of hypercholesterolemic rabbits showed
      850 differentially expressed genes (DEGs) in the cortex of hypercholesterolemic
      rabbits compared to controls, but only 5 DEGs in hypertensive rabbits compared to
      controls. Up-regulated genes in the PFC of hypercholesterolemic rabbits included
      CIDEC, ODF2, RNASEL, FSHR, CES3 and MAB21L3, and down-regulated genes included
      FAM184B, CUL3, LOC100351029, TMEM109, LOC100357097 and PFDN5. Comparison with our
      previous study on the middle cerebral artery (MCA) of the same rabbits showed
      many differentially expressed genes in common between the PFC and MCA, during
      hypercholesterolemia. Moreover, these genes tended to fall into the same
      functional networks, as revealed by IPA analyses, with many identical node
      molecules. These include: proteasome, insulin, Akt, ERK1/2, histone, IL12,
      interferon alpha and NFkappaB. Of these, PSMB4, PSMD4, PSMG1 were chosen as
      representatives of genes related to the proteasome for verification by
      quantitative RT-PCR. Results indicate significant downregulation of all three
      proteasome associated genes in the PFC. Immunostaining showed significantly
      increased number of Abeta labelled cells in layers III and V of the cortex after
      hypercholesterolemia and hypertension, which may be due to decreased proteasome
      activity and/or increased beta- or gamma-secretase activity. Knowledge of altered
      gene networks during hypercholesterolemia and/or hypertension could inform our
      understanding of the link between these conditions and cognitive deficits in
      vascular dementia or Alzheimer's disease.

PMID- 27890722
TI  - Diabetes-induced hepatic oxidative stress: a new pathogenic role for glycated
      albumin.
AB  - Increased oxidative stress and advanced glycation end-product (AGE) formation are
      major contributors to the development of type 2 diabetes. Here plasma proteins
      e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and
      related pathologies. However, despite recent progress linking albumin-AGE to
      increased oxidative stress and downstream effects, its action in metabolic organs
      such as the liver remains to be elucidated. The current study therefore
      investigated links between oxidative perturbations and biochemical/structural
      modifications of plasma albumin, and subsequent downstream effects in transgenic
      db/db mouse livers and HepG2 cells, respectively. Our data reveal increased
      oxidative stress biomarkers and lipid accumulation in plasma and livers of
      diabetic mice, together with albumin glycoxidation. Purified mouse albumin
      modifications resembled those typically found in diabetic patients, i.e. degree
      of glycation, carbonylation, AGE levels and in terms of chemical composition.
      Receptor for AGE expression and reactive oxygen species production were
      upregulated in db/db mouse livers, together with impaired proteolytic,
      antioxidant and mitochondrial respiratory activities. In parallel, acute exposure
      of HepG2 cells to glycated albumin also elicited intracellular free radical
      formation. Together this study demonstrates that AGE-modified albumin can trigger
      damaging effects on the liver, i.e. by increasing oxidative stress, attenuating
      antioxidant capacity, and by impairment of hepatic proteolytic and respiratory
      chain enzyme activities.

PMID- 27890724
TI  - Clinical characteristics and antimicrobial susceptibilities of anaerobic
      bacteremia in an acute care hospital.
AB  - This study investigated the clinical features of anaerobic bacteraemia in an
      acute-care hospital, and evaluated the antimicrobial susceptibility of these
      isolates to commonly available antibiotics. Microbiological and epidemiological
      data from 2009 to 2011were extracted from the laboratory information system and
      electronic medical records. One hundred and eleven unique patient episodes
      consisting of 116 anaerobic isolates were selected for clinical review and
      antibiotic susceptibility testing. Susceptibilities to amoxicillin-clavulanate,
      clindamycin, imipenem, metronidazole, moxifloxacin, penicillin and piperacillin
      tazobactam were performed using Etest strips with categorical interpretations
      according to current CLSI breakpoints. Metronidazole-resistant and carbapenem
      resistant anaerobic Gram-negative bacilli were screened for the nim and cfiA
      genes. Clinical data was obtained retrospectively from electronic medical
      records. During the 3 year period, Bacteroides fragilis group (41%), Clostridium
      species (14%), Propionibacterium species (9%) and Fusobacterium species (6%) were
      the most commonly isolated anaerobes. Patients with anaerobic bacteraemia that
      were included in the study were predominantly above 60 years of age, with
      community-acquired infections. The most commonly used empiric antibiotic
      therapies were beta-lactam/beta-lactamase inhibitor combinations (44%) and
      metronidazole (10%). The crude mortality was 25%, and appropriate initial
      antibiotic therapy was not significantly associated with improved survival. Intra
      abdominal infections (39%) and soft-tissue infections (33%) accounted for nearly
      three-quarters of all bacteraemia. Antibiotics with the best anaerobic activity
      were imipenem, piperacillin-tazobactam, amoxicillin-clavulanate and
      metronidazole, with in-vitro susceptibility rates of 95%, 95%, 94% and 92%
      respectively. Susceptibilities to penicillin (31%), clindamycin (60%) and
      moxifloxacin (84%) were more variable. Two multidrug-resistant isolates of
      Bacteroides species were positive for nim and cfiA genes respectively, while
      another two imipenem-resistant Fusobacterium species were negative for cfiA
      genes. This study demonstrated that anaerobic bacteraemia in our patient
      population was predominantly associated with intra-abdominal and soft-tissue
      infections. Overall antibiotic resistance was high for penicillin and
      clindamycin, and the presence of emerging resistance to carbapenems and
      metronidazole warrants further monitoring.

PMID- 27890726
TI  - Sources of antibiotics: Hot springs.
AB  - The discovery of antibiotics heralded an era of improved health care. However,
      the over-prescription and misuse of antibiotics resulted in the development of
      resistant strains of various pathogens. Since then, there has been an incessant
      search for discovering novel compounds from bacteria at various locations with
      extreme conditions. The soil is one of the most explored locations for
      bioprospecting. In recent times, hypersaline environments and symbiotic
      associations have been investigated for novel antimicrobial compounds. Among the
      extreme environments, hot springs are comparatively less explored. Many
      researchers have reported the presence of microbial life and secretion of
      antimicrobial compounds by microorganisms in hot springs. A pioneering research
      in the corresponding author's laboratory resulted in the identification of the
      antibiotic Fusaricidin B isolated from a hot spring derived eubacteria,
      Paenibacillus polymyxa, which has been assigned a new application for its anti
      tubercular properties. The corresponding author has also reported anti-MRSA and
      anti-VRE activity of 73 bacterial isolates from hot springs in India.

PMID- 27890727
TI  - Synthetic tambjamine analogues induce mitochondrial swelling and lysosomal
      dysfunction leading to autophagy blockade and necrotic cell death in lung cancer.
AB  - Current pharmacological treatments for lung cancer show very poor clinical
      outcomes, therefore, the development of novel anticancer agents with innovative
      mechanisms of action is urgently needed. Cancer cells have a reversed pH gradient
      compared to normal cells, which favours cancer progression by promoting
      proliferation, metabolic adaptation and evasion of apoptosis. In this regard, the
      use of ionophores to modulate intracellular pH appears as a promising new
      therapeutic strategy. Indeed, there is a growing body of evidence supporting
      ionophores as novel antitumour drugs. Despite this, little is known about the
      implications of pH deregulation and homeostasis imbalance triggered by ionophores
      at the cellular level. In this work, we deeply analyse for the first time the
      anticancer effects of tambjamine analogues, a group of highly effective anion
      selective ionophores, at the cellular and molecular levels. First, their effects
      on cell viability were determined in several lung cancer cell lines and patient
      derived cancer stem cells, demonstrating their potent cytotoxic effects. Then, we
      have characterized the induced lysosomal deacidification, as well as, the massive
      cytoplasmic vacuolization observed after treatment with these compounds, which is
      consistent with mitochondrial swelling. Finally, the activation of several
      proteins involved in stress response, autophagy and apoptosis was also detected,
      although they were not significantly responsible for the cell death induced.
      Altogether, these evidences suggest that tambjamine analogues provoke an
      imbalance in cellular ion homeostasis that triggers mitochondrial dysfunction and
      lysosomal deacidification leading to a potent cytotoxic effect through necrosis
      in lung cancer cell lines and cancer stem cells.

PMID- 27890725
TI  - Functional selectivity at G-protein coupled receptors: Advancing cannabinoid
      receptors as drug targets.
AB  - The phenomenon of functional selectivity, whereby a ligand preferentially directs
      the information output of a G-protein coupled receptor (GPCR) along (a)
      particular effector pathway(s) and away from others, has redefined traditional
      GPCR signaling paradigms to provide a new approach to structure-based drug
      design. The two principal cannabinoid receptors (CBRs) 1 and 2 belong to the
      class-A GPCR subfamily and are considered tenable therapeutic targets for several
      indications. Yet conventional orthosteric ligands (agonists, antagonists/inverse
      agonists) for these receptors have had very limited clinical utility due to their
      propensity to incite on-target adverse events. Chemically distinct classes of
      cannabinergic ligands exhibit signaling bias at CBRs towards individual subsets
      of signal transduction pathways. In this review, we discuss the known signaling
      pathways regulated by CBRs and examine the current evidence for functional
      selectivity at CBRs in response to endogenous and exogenous cannabinergic ligands
      as biased agonists. We further discuss the receptor and ligand structural
      features allowing for selective activation of CBR-dependent functional responses.
      The design and development of biased ligands may offer a pathway to therapeutic
      success for novel CBR-targeted drugs.

PMID- 27890728
TI  - The role of alkyl chain length of monothiol-terminated alkyl carboxylic acid in
      the synthesis, characterization, and application of gelatin-g-poly(N
      isopropylacrylamide) carriers for antiglaucoma drug delivery.
AB  - : To improve ocular bioavailability and extend pharmacological response, this
      study aims to investigate the role of alkyl chain length of monothiol-terminated
      alkyl carboxylic acids in the synthesis, characterization, and application of
      gelatin-g-poly(N-isopropylacrylamide) (GN) biodegradable in situ gelling carriers
      for antiglaucoma drug delivery. In the presence of mercaptoacetic acid (MAA),
      mercaptopropionic acid (MPA), mercaptobutyric acid (MBA), or mercaptohexanoic
      acid (MHA) as a chain transfer agent, the carboxylic end-capped poly(N
      isopropylacrylamide) samples were prepared by free radical polymerization
      technique. Our results showed that with increasing alkyl chain length, the
      hydrophobicity of thermo-responsive polymer segments significantly increased,
      mainly due to an increase in CH stretching frequencies. In addition, the greater
      hydrophobic association favored the decrease in both phase transition temperature
      and weight loss of GN copolymers, thereby accelerating their temperature
      triggered gelation process and retarding the degradation progress under
      physiological conditions. The benefits from these features allowed the
      pilocarpine carriers to increase drug payload and extend drug release.
      Irrespective of carbon number of monothiol-terminated alkyl carboxylic acid, the
      synthesized GN materials exhibited high tolerance to corneal endothelial cells
      without any evidence of inhibited proliferation, viability loss, inflammatory
      stimulation, and functional abnormality, indicating good biocompatibility.
      Results of clinical observations and histological examinations demonstrated that
      the therapeutic efficacies in treating glaucomatous damage are in response to in
      vivo drug release profiles from various intracamerally injected GN carriers. The
      research findings suggest the influence of alkyl chain length of chain transfer
      agent-mediated polymer hydrophobicity and degradability on pharmacological
      bioavailability and action of pilocarpine in a glaucomatous rabbit model.
      STATEMENT OF SIGNIFICANCE: Considering that glaucoma is a chronic disease that
      requires long-term medical therapy to preserve vision in patients, it is highly
      desirable to augment pharmacological bioavailability and govern release profile
      by tuning the properties of drug delivery carriers. For the first time, the
      present study provide striking evidence that the alkyl chain length of monothiol
      terminated alkyl carboxylic acid related to the synthesis of biodegradable in
      situ gelling copolymers plays a key role in molecular functionalization of
      intracameral delivery systems for ocular administration and controlled release of
      antiglaucoma medications. The therapeutic efficacies in treating glaucomatous
      damage are in response to in vivo pilocarpine release profiles modulated by the
      carbon number of thermo-responsive polymer segment-mediated carrier
      hydrophobicity and degradability.

PMID- 27890729
TI  - Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D
      collagen matrix: Effects of niche cell supplementation and mechanical
      stimulation.
AB  - : Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) are regarded
      as a promising source for regenerative medicine, drug testing and disease
      modeling. Nevertheless, cardiomyocytes are immature in terms of their contractile
      structure, metabolism and electrophysiological properties. Here, we fabricate
      cardiac muscle strips by encapsulating hESC-CMs in collagen-based biomaterials.
      Supplementation of niche cells at 3% to the number of hESC-CMs enhance the
      maturation of the hESC-CMs in 3D tissue matrix. The benefits of adding
      mesenchymal stem cells (MSCs) are comparable to that of adding fibroblasts. These
      two cell types demonstrate similar effects in promoting the compaction and cell
      spreading, as well as expression of maturation markers at both gene and protein
      levels. Mechanical loading, particularly cyclic stretch, produces engineered
      cardiac tissues with higher maturity in terms of twitch force, elastic modulus,
      sarcomere length and molecular signature, when comparing to static stretch or non
      stretched controls. The current study demonstrates that the application of niche
      cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D
      architecture. Our results therefore suggest that this 3D model can be used for in
      vitro cardiac maturation study. STATEMENT OF SIGNIFICANCE: Cardiomyocytes derived
      from human embryonic stem cells (hESC-CMs) are regarded as being a promising
      source of cells for regenerative medicine, drug testing and disease modeling.
      Nevertheless, cardiomyocytes are immature in terms of their contractile
      structure, metabolism and electrophysiological properties. In the current study,
      we have fabricated cardiac muscle strips by encapsulating hESC-CMs in collagen
      based biomaterials and demonstrated that supplementation of mesenchymal niche
      cells as well as provision of mechanical loading particularly stretching have
      significantly promoted the maturation of the cardiomyocytes and hence improved
      the mechanical functional characteristics of the tissue strips. Specifically,
      with 3% niche cells including both fibroblasts and mesenchymal stem cells, a more
      mature hESC-CMs derived cardiac strip was resulted, in terms of compaction and
      spreading of cells, and upregulation of molecular signature in both gene and
      protein expression of maturation. Mechanical loading, particularly cyclic
      stretch, produces engineered cardiac tissues with higher maturity in terms of
      molecular signature markers and functional parameters including twitch force,
      elastic modulus and sarcomere length, when comparing with static stretch or non
      stretched controls. The current study demonstrates that the application of niche
      cells and mechanical stretch both stimulate the maturation of hESC-CMs in 3D
      architecture, resulting in more mature cardiac strips. Our results contribute to
      bioengineering of functional heart tissue strips for drug screening and disease
      modeling.

PMID- 27890730
TI  - Cathodic voltage-controlled electrical stimulation of titanium for prevention of
      methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii biofilm
      infections.
AB  - : Antibiotic resistance of bacterial biofilms limits available treatment methods
      for implant-associated orthopaedic infections. This study evaluated the effects
      of applying cathodic voltage-controlled electrical stimulations (CVCES) of -1.5V
      and -1.8V (vs. Ag/AgCl) to coupons of commercially pure titanium (cpTi) incubated
      in cultures of methicillin-resistant Staphylococcus aureus (MRSA) and
      Acinetobacter baumannii (A. baumannii) as a method of preventing bacterial
      attachment. Stimulations were applied for 2, 4, and 8h and coupon-associated and
      planktonic colony-forming units (CFU) were enumerated following stimulation.
      Compared to open circuit potential (OCP) controls, CVCES for 4h at -1.8V
      significantly reduced coupon-associated MRSA CFU by 99.9% (1.30*104vs. 4.45*107,
      p=0.047) and A. baumannii coupon-associated CFU by 99.9% (1.64*104vs. 5.93*107,
      p=0.001) and reduced planktonic CFU below detectable levels for both strains.
      CVCES at -1.8V for 8h also reduced coupon-associated and planktonic CFU below
      detectable levels for each strain. CVCES at -1.5V for 4 and 8h, and -1.8V for 2h
      did not result in clinically relevant reductions. For 4 and 8h stimulations, the
      current density was significantly higher for -1.8V than -1.5V, an effect directly
      related to the rate of water and oxygen reduction on the cpTi surface. This
      significantly increased the pH, a suspected influence in decreased CFU viability.
      The voltage-dependent electrochemical properties of cpTi likely contribute to the
      observed antimicrobial effects of CVCES. This study revealed that CVCES of
      titanium could prevent coupon-associated and planktonic CFU of Gram-positive MRSA
      and Gram-negative A. baumannii from reaching detectable levels in a magnitude
      dependent and time-dependent manner. STATEMENT OF SIGNIFICANCE: Periprosthetic
      joint infection is a devastating outcome of total joint arthroplasty and has led
      to increased patient morbidity and rising healthcare costs. Current treatments
      are limited by the growing prevalence of antimicrobial resistant biofilms.
      Therefore, there is a growing interest in the prevention of bacterial
      colonization of implants. Previous work has shown that cathodic voltage
      controlled electrical stimulation (CVCES) of titanium is effective both in vitro
      and in vivo as an antimicrobial strategy to eradicate established implant
      associated biofilm infections. The present study revealed that CVCES of titanium
      coupons also has utility in preventing coupon-associated and planktonic colony
      forming units of Gram-positive methicillin-resistant Staphylococcus aureus and
      Gram-negative Acinetobacter baumannii from reaching detectable levels in a
      magnitude-dependent and time-dependent manner.

PMID- 27890731
TI  - Mechanisms of Cdc42-mediated rat MSC differentiation on micro/nano-textured
      topography.
AB  - : Micro/nano-textured titanium surface topography promotes osteoblast
      differentiation and the Wnt/beta-catenin signaling pathway. However, the response
      of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and
      the underlying mechanisms of its effects, are not well understood. We
      hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho
      GTPases family, may regulate rat MSCs morphology and osteogenic differentiation
      by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/beta
      catenin is the underlying mechanism. To confirm the hypothesis, we first tested
      rat MSCs' morphology, cytoskeleton, and osteogenic differentiation on micro/nano
      textured topography. We then examined the cells' Wnt pathway and Cdc42 signaling
      activity. The results show that micro/nano-textured topography enhances MSCs'
      osteogenic differentiation. In addition, the cells' morphology and cytoskeletal
      reorganization were dramatically different on smooth surfaces and
      micropitted/nanotubular topography. Ligands of the canonical Wnt pathway, as well
      as accumulation of beta-catenin in the nucleus, were up-regulated by micro/nano
      textured topography. Cdc42 protein expression was markedly increased under these
      conditions; conversely, Cdc42 silencing significantly depressed the enhancement
      of MSCs osteogenic differentiation by micro/nano-textured topography. Moreover,
      Cdc42si attenuated p-GSK3beta activation and resulted in beta-catenin cytoplasmic
      degradation on the micro/nano-textured topography. Our results indicate that
      Cdc42 is a key modulator of rat MSCs morphology and cytoskeletal reorganization,
      and that crosstalk between Cdc42 and Wnt/beta-catenin signaling though GSK3beta
      regulates MSCs osteogenic differentiation by implant topographical cues.
      STATEMENT OF SIGNIFICANCE: Topographical modification at micro- and nanoscale is
      widely applied to enhance the tissue integration properties of biomaterials.
      However, the response of bone mesenchymal stem cells (MSCs) to the micro/nano
      textured topography and the underlying mechanisms are not well understood. This
      study shows that the micropitted/nanotubular hierarchical topography produced by
      etching and anodic oxidation treatment drives fusiform cell morphology,
      cytoskeletal reorganization as well as better MSCs osteogenic differentiation.
      The cross-talk between Cdc42 pathway and Wnt/beta-catenin pathway though GSK3beta
      modulates the osteoinductive effect of the micro/nano-textured topography on
      MSCs. This finding sheds light on a novel mechanism involved in micro/nano
      textured surface-mediated MSCs osteogenic differentiation and is a major step in
      the development of new surface modifications aiming to accelerate and enhance the
      process of osseointegration.

PMID- 27890732
TI  - Programmed near-infrared light-responsive drug delivery system for combined
      magnetic tumor-targeting magnetic resonance imaging and chemo-phototherapy.
AB  - : In this study, an intelligent drug delivery system was developed by capping
      doxorubicin (DOX)-loaded hollow mesoporous CuS nanoparticles (HMCuS NPs) with
      superparamagnetic iron oxide nanoparticles (IONPs). Under near infrared (NIR)
      light irradiation, the versatile HMCuS NPs could exploit the merits of both
      photothermal therapy (PTT) and photodynamic therapy (PDT) simultaneously. Herein,
      the multifunctional IONPs as gatekeeper with the enhanced capping efficiency were
      supposed to realize "zero premature release" and minimize the adverse side
      effects during the drug delivery in vivo. More importantly, the hybrid metal
      nanoplatform (HMCuS/DOX@IONP-PEG) allowed several emerging exceptional
      characteristics. Our studies have substantiated the hybrid nanoparticles
      possessed an enhanced PTT effect due to coupled plasmonic resonances with an
      elevated heat-generating capacity. Notably, an effective removal of IONP-caps
      occurred after NIR-induced photo-hyperthermia via weakening of the coordination
      interactions between HMCuS-NH2 and IONPs, which suggested the feasibility of
      sophisticated controlled on-demand drug release upon exposing to NIR stimulus
      with spatial/temporal resolution. Benefiting from the favorable magnetic tumor
      targeting efficacy, the in vitro and in vivo experiments indicated a remarkable
      anti-tumor therapeutic efficacy under NIR irradiation, resulting from the
      synergistic combination of chemo-phototherapy. In addition, T2-weighted magnetic
      resonance imaging (MRI) contrast performance of IONPs provided the identification
      of cancerous lesions. Based on these findings, the well-designed drug delivery
      system via integration of programmed functions will provide knowledge for
      advancing multimodality theranostic strategy. STATEMENT OF SIGNIFICANCE: As we
      all know, a series of shortcomings of conventional chemotherapy such as limited
      stability, rapid clearing and non-specific tumor targeting ability remain a
      significant challenge to achieve successful clinical therapeutic efficiency in
      cancer treatments. Fortunately, developing drug delivery system under the
      assistance of multifunctional nanocarries might be a great idea. For the first
      time, we proposed an intelligent drug delivery system by capping DOX-loaded
      hollow mesoporous CuS nanoparticles (HMCuS NPs) with multifunctional IONPs to
      integrate programmed functions including enhanced PTT effect, sophisticated
      controlled drug release, magnetic targeting property and MR imaging. The results
      showed HMCuS/DOX@IONP-PEG could significantly enhance anti-tumor therapeutic
      efficacy due to the synergistic combination of chemo-phototherapy. By this
      delicate design, we believe such smart and extreme versatile all-in-one drug
      delivery platform could arouse broad interests in the fields of biomaterials,
      nanotechnology, and drug delivery system.

PMID- 27890733
TI  - Differences in the onset mode of ventricular tachyarrhythmia between patients
      with J wave in anterior leads and those with J wave in inferolateral leads.
AB  - BACKGROUND: The pathophysiological mechanism of J wave in anterior leads (A
      leads) and inferolateral leads (L-leads) remains unclear. OBJECTIVE: We
      investigated the onset mode and circadian distribution of ventricular
      tachyarrhythmia (VTA) episodes between patients with early repolarization
      syndrome (ERS) and Brugada syndrome (BrS). METHODS: The study enrolled 35
      patients with ERS and 52 patients with type 1 BrS with spontaneous ventricular
      fibrillation who were divided into 4 groups: ERS(A+L) (n = 15), patients with ERS
      who had a non-type 1 Brugada pattern electrocardiogram in any A-leads (second to
      fourth intercostal spaces) in control and/or after drug provocation tests; ERS(L)
      (n = 20), patients with ERS with J wave only in L-leads; BrS(A) (n = 24),
      patients with BrS without J wave in L-leads; and BrS(A+L) (n = 28), patients with
      BrS with J wave in L-leads. The onset mode of 206 VTAs obtained from
      electrocardiograms or implantable cardioverter-defibrillators and the circadian
      distribution of 352 VTAs were investigated in the 4 groups. RESULTS: Three groups
      with J wave in A-leads, ERS(A+L), BrS(A), and BrS(A+L), had higher incidences of
      nocturnal (63%, 43%, and 47%, respectively) and sudden onset VTAs (67%, 97%, and
      86%, respectively) with longer coupling intervals of premature ventricular
      contractions (388.8, 397.3, and 385.6 ms, respectively) than the ERS(L) group
      with J wave only in L-leads (25%, P = .0019; 19%, P < .0001; and 330.6 ms, P =
      .0004, respectively), the last of which mainly displayed VTAs with a short-long
      short sequence. CONCLUSION: The onset mode of VTAs was different between patients
      with J wave in A-leads and patients with J wave in only L-leads. The underlying
      mechanism of J wave may differ between A-leads and L-leads.

PMID- 27890734
TI  - Catheter ablation and the left atrial appendage: Should we embrace isolation?

PMID- 27890735
TI  - Variability in obstructive sleep apnea: Analysis of pacemaker-detected
      respiratory disturbances.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with several
      cardiovascular conditions. Some pacemakers feature specific algorithms detecting
      respiratory cycles and deriving indices well correlated with the identification
      of polysomnography-confirmed severe OSA. OBJECTIVES: The purposes of this study
      were to analyze respiratory disturbances measured by a validated algorithm in
      clinical practice and to describe their variability over time and their
      association with atrial fibrillation. METHODS: Fifty-eight patients implanted
      with dual-chamber LivaNova REPLY 200 DR or KORA 100 DR pacemakers measuring a
      respiratory disturbance index (RDI) were included. An RDI >20 events per hour of
      sleep is well correlated with severe OSA as determined by polysomnography.
      Patients with >10% nights with invalid RDI measurements were excluded. RESULTS:
      The RDI could be measured during 98% of nights. During a mean follow-up of 187 +/
      123 days, the individual mean RDI was 19.9 +/- 12.7 and was superior to 20 in 24
      patients (41%). An RDI >20 events/h in at least 1 night was observed in 52
      patients (90%). The mean day-to-day RDI variability in individual patients was
      19% +/- 21%. Patients with the highest burden of severe OSA (as defined by >=75%
      of nights with RDI >20 events/h) were older, had a higher prevalence of
      hypertension, and were more often implanted for atrioventricular block than
      patients with lower burden of severe OSA. No RDI burden or cutoff was a predictor
      of atrial fibrillation occurrence. CONCLUSION: OSA is frequent in patients with a
      pacemaker and is reliably detected by pacemakers. OSA is highly variable and
      could probably be best analyzed in terms of burden.

PMID- 27890736
TI  - To the Editor- Perioperative anticoagulation management during thoracoscopic
      ablation.

PMID- 27890737
TI  - Reply to the Editor-Perioperative anticoagulation management during thoracoscopic
      ablation.

PMID- 27890738
TI  - Ventricular arrhythmias associated with left ventricular noncompaction:
      Electrophysiologic characteristics, mapping, and ablation.
AB  - BACKGROUND: Left ventricular noncompaction (LVNC) is a primary cardiomyopathy
      that can present with recurrent ventricular arrhythmias (VAs). Data on the
      benefit of catheter ablation of VAs in LVNC are lacking. OBJECTIVE: The purpose
      of this study was to describe the electrophysiologic features and outcomes of
      catheter ablation of VAs in LVNC. METHODS: The cohort consisted of 9 patients
      (age 42 +/- 15 years) with diagnosis of LVNC based on established criteria and VA
      (ventricular tachycardia [VT] in 3 and frequent premature ventricular
      contractions (PVCs) in 6) despite treatment with a mean of 2 +/- 1 antiarrhythmic
      drugs. Ablation sites were identified using a combination of entrainment,
      activation, late/fractionated potential ablation, and pace-mapping. RESULTS: A
      total of 8 patients (89%) had left ventricular (LV) systolic dysfunction (mean
      ejection fraction 40% +/- 13%). Patients who presented with VT had evidence of
      abnormal electroanatomic substrate involving the mid- to apical segments of the
      LV, which matched the noncompacted myocardial segments identified by
      preprocedural magnetic resonance imaging or echocardiography. In patients
      presenting with frequent PVCs, the site of origin was identified at the papillary
      muscles (50%) and/or basal septal regions (67%). After median follow-up of 4
      years (range 1-11) and a mean of 1.8 +/- 1.1 procedures, VAs recurred in 1
      patient (11%). Significant improvement in LV function occurred in 4 of 8 cases
      (50%). No patients died or underwent heart transplantation. CONCLUSION: The VA
      substrate in patients with LVNC and VT typically involves the mid-apical LV
      segments, whereas focal PVCs often arise from LV basal-septal regions and/or
      papillary muscles. Catheter ablation is safe and effective in achieving good VA
      control over long-term follow-up in most patients.

PMID- 27890739
TI  - Novel insights into the mechanisms of renal sympathetic denervation-induced
      neuromodulation in controlling atrial arrhythmias in canines.

PMID- 27890740
TI  - Rotor mapping and ablation: Spinning out of control?

PMID- 27890741
TI  - Perisylvian GABA levels in schizophrenia and bipolar disorder.
AB  - The aim of this study is to measure GABA levels of perisylvian cortices in
      schizophrenia and bipolar disorder patients, using proton magnetic resonance
      spectroscopy (1H-MRS). Patients with schizophrenia (n=25), bipolar I disorder (BD
      I; n=28) and bipolar II disorder (BD-II; n=20) were compared with healthy
      controls (n=30). 1H-MRS data was acquired using a Siemens 3T whole body scanner
      to quantify right and left perisylvian structures' (including superior temporal
      lobes) GABA levels. Right perisylvian GABA values differed significantly between
      groups [chi2=9.62, df: 3, p=0.022]. GABA levels were significantly higher in the
      schizophrenia group compared with the healthy control group (p=0.002).
      Furthermore, Chlorpromazine equivalent doses of antipsychotics correlated with
      right hemisphere GABA levels (r2=0.68, p=0.006, n=33). GABA levels are elevated
      in the right hemisphere in patients with schizophrenia in comparison to bipolar
      disorder and healthy controls. The balance between excitatory and inhibitory
      controls over the cortical circuits may have direct relationship with GABAergic
      functions in auditory cortices. In addition, GABA levels may be altered by brain
      regions of interest, psychotropic medications, and clinical stage in
      schizophrenia and bipolar disorder.

PMID- 27890742
TI  - Serum uric acid and impaired cognitive function in community-dwelling elderly in
      Beijing.
AB  - The relationship between serum uric acid (sUA) and cognitive function is
      contradictory. This study assessed the association between sUA and cognitive
      impairment in 10,039 community-dwelling subjects aged >=55years living in
      Beijing, China. Participants underwent determination of sUA and an evaluation of
      cognitive function using the scholarship-adjusted Mini-Mental State Examination
      (MMSE): MMSE <=17 for illiterates; MMSE<=20 for primary school graduates
      (>=6years of education); and MMSE<=24 for junior school graduates or above
      (>=9years of education). Among the 10016 persons with valid MMSE scores, the
      prevalence of cognitive impairment was 9.14%. A multivariate logistic regression
      model including demographic, clinical and genetic parameters was performed to
      assess the relationship between sUA and cognitive impairment. Persons with
      cognitive impairment had lower sUA levels than those with normal cognitive
      function: (302.30+/-82.80 vs. 312.20+/-84.01MUmol/L, p=0.001). After adjusting
      for age, sex, lifestyle, relevant diseases and the apolipoprotein E (APOE)
      epsilon4 allele, stepwise logistic regression showed that participants with
      higher levels of sUA had a lower risk of cognitive impairment (hazard ratio (HR):
      0.78; 95% confidence interval (CI): 0.62-0.96; p=0.022). In this baseline cross
      sectional population-based sample, high levels of sUA were associated with a
      decreased risk of cognitive impairment.

PMID- 27890743
TI  - Considering future pharmacotherapy for PTSD.
AB  - Posttraumatic stress disorder (PTSD) is a prevalent, disabling, and often chronic
      condition that may develop following exposure to a traumatic event. Despite the
      immense social and economic ramifications of PTSD, there has been relatively
      little recent development of new pharmacotherapies. The majority of
      pharmacological randomized clinical trials (RCTs) that has been conducted are now
      dated. Existing treatments for PTSD primarily have come out of research that
      tested medications developed for other disorders such as antidepressants, anti
      hypertensives, antipsychotics, anticonvulsants, and anxiolytics. With an improved
      understanding of the complex pathophysiology of PTSD, we consider why it has
      taken so long to identify important targets to advance the field by addressing
      the underlying pathophysiology in pharmacological interventions. Exciting
      developments include research into PTSD-related abnormalities associated with
      dysregulation of adrenergic, hypothalamic-pituitary-adrenocortical,
      monoaminergic, peptide, glutamatergic, GABAergic, cannabinoid, opioid, and other
      neurotransmitter and neuroendocrine systems. Yet, this is a broad list and there
      are many unanswered questions. Current research on biomarkers associated with
      different clinical phenotypes of PTSD should lead to novel and more specific
      pharmacotherapeutic strategies. In this brief review, we consider key questions
      regarding current knowledge on pharmacological treatments for PTSD and highlight
      evolving practices in future research.

PMID- 27890744
TI  - Gene expression of pro-opiomelanocortin and melanocortin receptors is regulated
      in the hypothalamus and mesocorticolimbic system following nicotine
      administration.
AB  - Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown
      to play important roles in natural and drug-induced reward and reinforcement.
      Reward process may involve the regulation of POMC gene expression and the gene
      expression of POMC-derived peptide receptors. The present study investigated the
      alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R),
      melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and
      mesocorticolimbic system during nicotine exposure. Rats were injected
      subcutaneously for 5days with one of the three doses (0.2, 0.4 or 0.6mg/kg/day,
      free base) of nicotine and were decapitated one hour after a challenge dose on
      the sixth day. mRNA levels of POMC in the hypothalamus, MC3R in the ventral
      tegmental area (VTA), MC4R and MOR in the medial prefrontal cortex (mPFC),
      nucleus accumbens, dorsal striatum, amygdala, lateral hypothalamic area and VTA
      were measured by quantitative real-time PCR. Our results showed that treatment
      with 0.6mg/kg/day nicotine upregulated POMC mRNA in the hypothalamus and MC4R
      mRNA in the mPFC. Additionally, all three nicotine doses increased MC3R mRNA
      expression in the VTA. On the other hand, none of the nicotine doses altered MOR
      mRNA levels in the mesocorticolimbic system and associated limbic structures.
      These results suggest that nicotine may enhance melanocortin signaling in the
      mesocorticolimbic system and this alteration may be an important mechanism
      mediating nicotine reward.

PMID- 27890745
TI  - Mini-Open Thoracolumbar Corpectomy: Perioperative Outcomes and Hospital Cost
      Analysis Compared with Open Corpectomy.
AB  - BACKGROUND: Standard open surgical management of thoracolumbar infection, trauma,
      and tumor is associated with significant morbidity. We compared perioperative and
      immediate postoperative morbidity of open and mini-open thoracolumbar corpectomy
      techniques including direct hospital costs. METHODS: We retrospectively reviewed
      medical records of all patients who underwent open or mini-open corpectomy.
      Demographics (age, sex, body mass index, primary diagnosis), operative data
      (length of surgery, estimated blood loss, blood transfusion), surgical level,
      preoperative and postoperative neurologic status (using American Spinal Injury
      Association Impairment Scale), immediate perioperative complications (within 30
      days postoperatively), overall length of stay from admission, length of stay from
      surgery, and total direct hospital costs were tabulated and analyzed. RESULTS:
      The study included 43 patients, 20 (46.51%) undergoing open corpectomy and 23
      (53.48%) undergoing mini-open corpectomy. Clinical and statistically significant
      findings in favor of mini-open corpectomy included lower estimated blood loss
      (1305 mL vs. 560 mL, P = 0.0072), less blood transfusion (241 mL vs. 667 mL, P =
      0.029), shorter overall length of stay (7.2 days vs. 12.2 days, P = 0.047), and
      shorter surgery time (376 minutes vs. 295 minutes, P = 0.035) as well as lower
      total direct hospital cost ($34,373 vs. $45,376, P = 0.044). There was no
      statistically significant difference in postoperative complications between the 2
      groups (medical complications 5% vs. 4.3%, P = 0.891; surgical complications 5%
      vs. 8.69%, P = 0.534). CONCLUSIONS: Mini-open TL corpectomy is a safe, cost
      effective, clinically effective, and less morbid alternative to standard open
      thoracotomy surgical techniques.

PMID- 27890746
TI  - Treatment Strategy for Isolated Posterior Inferior Cerebellar Artery Dissection.
AB  - OBJECTIVE: Isolated dissections that develop on the posterior inferior cerebellar
      artery (PICA) require intensive treatment because of their potential fatality.
      However, because of the rarity of these dissections, the optimal treatment has
      not yet been established. METHODS: We retrospectively reviewed the clinical
      records of all patients who underwent any PICA dissection treatment in our
      institute over the last 4 years. Ten patients were enrolled, including 7 patients
      with subarachnoid hemorrhage (SAH) and 3 with PICA territory infarction.
      Dissection was seen at the proximal portion in 8 patients, whereas the remaining
      2 patients showed distal PICA dissecting aneurysms. RESULTS: Among the 7 patients
      with hemorrhage, 5 were actively treated (trapping and bypass, 2 patients;
      surgical clipping, 1 patient; coil embolization, 2 patients). Conservative
      management was performed in the other 2 patients. Among the 3 patients with
      infarction, 2 received conservative treatment. Endovascular treatment was
      performed in 1 patient, who showed rapid progression, aneurysm formation, and
      conversion to massive SAH within 10 days after the initial attack. Although 7
      patients showed relatively good outcomes (modified Rankin Scale score, <=2) after
      30 days of follow-up, 1 patient had a final modified Rankin Scale score of 3. In
      addition, the other 2 patients (1 in each group) died as a result of major SAH.
      CONCLUSIONS: Given the dynamic clinical course and potential fatality of PICA
      dissection, meticulous evaluation, intensive treatment with a diverse range of
      modalities, and proper follow-up are required for patients with PICA dissection
      to achieve favorable outcomes.

PMID- 27890747
TI  - Delayed Visual Loss and Its Surgical Rescue Following Extracranial-Intracranial
      Arterial Bypass and Native Internal Carotid Artery Sacrifice.
AB  - BACKGROUND: High-flow extracranial-intracranial (EC-IC) bypass followed by
      sacrifice of the native internal carotid artery (ICA) is a recognized treatment
      option for giant ICA aneurysm and skull base tumor involving the ICA. Distal
      clipping at the supraclinoid portion of the ICA is technically straightforward,
      but it can potentially compromise ophthalmic artery (OA) perfusion. Because of
      the extensive EC-IC anastomoses with the OA, visual symptoms are fortunately
      uncommon. We report a patient who developed complete blindness after distal
      trapping of the supraclinoid ICA; it was reversed after emergency clip removal.
      CASE DESCRIPTION: Our patient is a 47-year-old man with recurrent nasopharyngeal
      carcinoma in close proximity to the left petrosal ICA. The first stage of the
      procedure involved an EC-IC bypass using radial artery graft, followed by a
      second stage with combined craniofacial excision. Trapping of the native ICA was
      achieved using a permanent aneurysm clip placed at the supraclinoid ICA distal to
      the origin of the OA. He complained of a new onset of complete left eye visual
      loss approximately 6 hours after the distal aneurysm clip was applied. He was
      immediately sent to the operating theatre for the removal of the supraclinoid
      aneurysm clip. On the next day, his vision improved and left pupil became
      reactive again. DISCUSSION: OA flow following ICA trapping is complicated and
      precarious. Delayed onset of visual loss is possible. Prompt action by direct
      exploration and clip removal is needed and can be effective in reversing
      blindness.

PMID- 27890748
TI  - Small Unruptured Intracranial Aneurysm (<=5 mm) Associated with Epilepsy: Report
      of 2 Cases and Literature Review.
AB  - BACKGROUND: Owing to the continuing improvements in imaging technology, an
      increasing number of epileptogenic small (<=5 mm) unruptured intracranial
      aneurysms (sUIAs) are being diagnosed. However, these sUIAs have not been
      systematically described and reviewed until now. CASE DESCRIPTION AND LITERATURE
      REVIEW: We report 2 patients with sUIAs who initially presented with complex
      partial seizures. Scalp electroencephalography identified the seizure activity as
      arising from the mesial temporal/frontal areas, but conventional magnetic
      resonance imaging (MRI) was normal in both patients. The diagnosis of sUIA was
      achieved by cerebral angiography. One of the patients had idiopathic seizures and
      sustained a subarachnoid hemorrhage before the final diagnosis of sUIA. Both of
      the patients were treated by surgical clipping without resection of the adjacent
      discolored brain tissue, and the seizures were controlled after surgery.
      Furthermore, we thoroughly reviewed the relevant literature. We analyzed a total
      of 5 documented cases, including out 2 cases, and described the clinical
      characteristics, diagnosis, underlying mechanism, treatment, and prognosis of
      epileptogenic sUIA. CONCLUSIONS: The seizures caused by sUIAs are most likely
      related to subclinical hemorrhages. Angiography may be helpful in identifying
      seizures associated with sUIA in patients with normal conventional MRI findings.
      For epileptogenic sUIA with normal preoperative MRI, clipping without damaging
      the surrounding brain tissue may be sufficient to resolve this complex issue.

PMID- 27890749
TI  - The Medial and Lateral Lemnisci: Anatomically Adjoined But Functionally Distinct
      Fiber Tracts.
AB  - OBJECTIVE: The dense and complex distribution of neural structures in the
      brainstem makes it challenging to understand their real configuration. We used
      the fiber microdissection technique to show the course of the medial and lateral
      lemnisci within the brainstem. Although these structures seem anatomically alike,
      they are functionally distinct. METHODS: Fifteen human brainstems and 8 brain
      hemispheres (formalin-fixed and previously frozen) were dissected and studied
      under the operating microscope by applying the fiber microdissection technique.
      RESULTS: We delineated and described the medial and lateral lemnisci, noting
      their gross elaborate arrangement. These structures are intimately compact and
      closely related to one another in their common trajectory through the tegmenta of
      the pons and midbrain. However, we were not able to identify the exact origin and
      termination of their fibers or the accurate delimitation between the medial
      lemniscus, spinothalamic tract, and lateral lemniscus along their course in the
      brainstem. CONCLUSIONS: Using the fiber microdissection technique, we were able
      to define a general perspective of the topography and architecture of the medial
      and lateral lemnisci in the brainstem. This perspective should be incorporated
      into interpretations of magnetic resonance imaging techniques, recognizing both
      their benefits and limitations. It should also be applied to surgical planning
      and strategies to achieve a safer and more precise microsurgical procedure.

PMID- 27890750
TI  - The Use of Social Media Communications in Brain Aneurysms and Subarachnoid
      Hemorrhage: A Mixed-Method Analysis.
AB  - BACKGROUND: The diagnosis of a ruptured or unruptured brain aneurysm has a
      significant impact on patients' quality of life and their psychosocial well
      being. As a result, patients and caregivers may resort to social media platforms
      for support and education. The aim of this report is to evaluate the use of
      social media and the online communications regarding brain aneurysms. METHODS:
      Three social media platforms (Facebook, Twitter, and YouTube) were assessed for
      public content pertaining to brain aneurysms in March 2016. We conducted a mixed
      method analysis that includes a descriptive examination of cross-sectional data
      and a qualitative evaluation of online communications for thematic analysis. We
      assessed categorized data using nonparametric tests for statistical significance.
      RESULTS: Our analyses showed that Facebook was the most highly used social media
      platform, with 11 relevant pages and 83 groups. Facebook accounts were all
      nonprofit foundations or patient support groups. Most users in Facebook groups
      were joining private support groups as opposed to public (P < 0.05). The most
      frequently viewed category of YouTube videos was on treatment procedures (P <
      0.001). Six prominent themes emerged from the coded data of posts and comments:
      inspiration and motivation (27.7%), providing and sharing information (26.3%),
      requesting information (14.4%), seeking emotional support (12.1%), admiration
      (8.3%), and loss and grief (8.3%). CONCLUSIONS: This study is the first to
      provide insight into characteristics and patterns of social media communications
      regarding brain aneurysms. These findings should serve to inform the treating
      physicians of the needs and expectations of individuals affected by brain
      aneurysms.

PMID- 27890751
TI  - Atlantoaxial Fixation for Basilar Invagination without Obvious Atlantoaxial
      Instability (Group B Basilar Invagination): Outcome Analysis of 63 Surgically
      Treated Cases.
AB  - BACKGROUND: We discuss the rationale of surgical treatment of group B basilar
      invagination by atlantoaxial facet joint stabilization and segmental arthrodesis.
      METHODS: From January 2010 to April 2016, 63 patients with group B basilar
      invagination were surgically treated. All patients had varying degree of
      myelopathy-related functional disability. Fifty-two patients had both Chiari
      malformation and syringomyelia. All patients were treated by atlantoaxial plate
      and screw fixation with the techniques described by us in 1994 and 2004. Foramen
      magnum decompression or syrinx manipulation was not carried out in any patient.
      Occipital bone and subaxial spinal elements were not included in the fixation
      construct. RESULTS: Three patients died in the immediate postoperative phase. In
      the remaining patients, there was clinical improvement and no patient's
      neurologic function worsened after surgery. In 12 of 38 patients in whom
      postoperative magnetic resonance imaging was possible, at a follow-up of at least
      3 months, there was reduction in the size of the syrinx. CONCLUSIONS: The
      pathogenesis of basilar invagination in group B is related to atlantoaxial
      instability. The clinical outcome suggests that the surgical treatment in these
      cases should be directed toward atlantoaxial stabilization and aimed at segmental
      arthrodesis. Inclusion of the occipital bone in the fixation construct is not
      necessary. Foramen magnum decompression and procedures involving manipulation of
      Chiari malformation and syringomyelia are not necessary.

PMID- 27890752
TI  - Delayed Development of Aneurysms Following Gamma Knife Surgery for Trigeminal
      Neuralgia: Report of 2 Cases.
AB  - BACKGROUND: Delayed development of intracranial aneurysms is an extremely rare
      complication of gamma knife surgery (GKS), with only 6 cases been reported to
      date. There are no reported cases after GKS performed to treat trigeminal
      neuralgia (TN). Of the 6 aforementioned cases, none referred to the natural
      history or pathophysiology of GKS-related intracranial aneurysm formation. CASE
      DESCRIPTION: We treated 2 patients with subarachnoid hemorrhage (SAH) resulting
      from rupture of an intracranial aneurysm that developed long after GKS. Case 1
      involved a 77-year-old man who had undergone GKS to treat recurrent TN after
      microvascular decompression surgery. At 13 years after the GSK, he developed SAH
      from a ruptured left anterior inferior cerebellar artery in close vicinity to the
      left trigeminal nerve. He died from a premature rupture before intervention could
      be instituted. Case 2 involved a 72-year-old woman who developed SAH at 9 years
      after undergoing GKS for TN. A ruptured left superior cerebellar artery aneurysm
      was treated successfully with endovascular occlusion of the parent artery. She
      recovered well after the surgery, and was discharged to the rehabilitation
      hospital with a modified Rankin Scale score of 2. CONCLUSION: Long-term
      observations are necessary after GKS performed for TN owing to the possibility of
      formation of intracranial aneurysms near the irradiated region.

PMID- 27890753
TI  - Geographically Remote Cerebral Venous Sinus Thrombosis in Patients with
      Intracranial Tumors.
AB  - Cerebral venous sinus thrombosis (CVST) related to intracranial tumors has most
      commonly been recognized as an operative complication related to local operative
      factors such as retraction or direct venous injury. CVST may also be caused by
      tumor-related factors such as local mass effect but rarely occurs geographically
      remote from the site of the tumor. We report 6 cases treated at our institution
      of intracranial supratentorial tumors associated with CVST. In each case, the
      CVST was remote from the surgical site. In 3 cases CVST was noted at the time of
      resection, and 3 cases occurred in a delayed fashion. Each case is discussed in
      detail, and the utility of intraoperative magnetic resonance imaging in the early
      diagnosis of this complication is highlighted.

PMID- 27890754
TI  - Endovascular Treatment of Spontaneous Intracranial Fusiform and Dissecting
      Aneurysms: Outcomes Related to Imaging Classification of 309 Cases.
AB  - OBJECTIVE: To propose a modified classification system for spontaneous
      intracranial dissecting aneurysms (IDAs) that can guide treatment decisions.
      METHODS: Between January 2010 and December 2015, 3183 consecutive patients were
      referred to our department for endovascular treatment of a cerebral aneurysm.
      Among this group, 309 patients harboring a total of 323 spontaneous IDAs were
      identified. Based on a modified imaging classification system, spontaneous IDAs
      were classified into 4 subtypes: classic dissecting aneurysm, segmental ectasia,
      dolichoectatic dissecting aneurysm, and large mural bleeding ectasia. A logistic
      regression analysis was conducted to identify predictors of clinical outcomes.
      RESULTS: Of the 323 IDAs, 216 (66.87%) were treated with stent-assisted coiling,
      47 (14.55%) with internal trapping, and 60 (18.58%) with sole stenting. Of the
      309 patients, 8 (2.59%) suffered intraoperative complications, 40 (12.94%)
      experienced postoperative complications, 9 died (2.79%), and 1 (0.32%) had severe
      disability. The mean duration of clinical follow-up of the 309 patients was 10.40
      months (range, 3-72 months). Imaging follow-up was available for 262 patients
      (274 IDAs), with a mean duration of 7.10 months (range, 3-60 months), and 24
      aneurysm recurrences (9.16%) were noted. Aneurysm type was the sole independent
      predictor of different outcomes on logistic regression analysis (P = 0.004).
      CONCLUSIONS: There was a strong relationship between the subtypes of spontaneous
      IDAs and clinical course. Our classification system is confirmed to be helpful in
      assessing patients' prognosis and guiding their treatment.

PMID- 27890755
TI  - Predictors of Shunt Insertion in Aneurysmal Subarachnoid Hemorrhage.
AB  - OBJECTIVE: Hydrocephalus is a common complication of aneurysmal subarachnoid
      hemorrhage (aSAH), requiring permanent cerebrospinal fluid (CSF) diversion in up
      to two thirds of patients. Factors that predict permanent CSF diversion are not
      well established. METHODS: An exploratory analysis of 149 patients enrolled in
      the CARAS (Cerebral Aneurysm Renin Angiotensin System) study was performed in an
      effort to identify factors predictive of permanent CSF diversion after aSAH; only
      the 135 patients surviving the initial hospitalization were included in the
      present study. CARAS was a prospective, multicenter study investigating the
      impact of genetic polymorphisms in patients with aSAH and enrolled patients from
      September 2012 to January 2015. RESULTS: One hundred and forty-nine patients with
      aSAH were enrolled in CARAS, with 135 (90.6%) patients surviving the initial
      hospitalization. Sixty-four of these patients (47.4%) required permanent CSF
      diversion. Multivariable analysis identified the following as independent risk
      factors: sympathomimetic illicit drug use, external ventricular drain (EVD)
      insertion, and hyponatremia. A scoring system based on EVD insertion (2 points),
      Hunt and Hess grade (1 point if grade >=4) and modified Fisher computed
      tomography grade (1 point if grade 4) produced an area under the curve of 0.8 (P
      < 0.001). CONCLUSIONS: Sympathomimetic illicit drug use, EVD insertion, and
      hyponatremia are the strongest predictors of shunt insertion in patients with
      aSAH. Moreover, a scoring system based on EVD insertion, Hunt and Hess grade, and
      modified Fisher computed tomography grade can reliably predict the need for shunt
      placement in patients with aSAH.

PMID- 27890756
TI  - Cavernous Angioma of the Cerebral Aqueduct.
AB  - BACKGROUND: Among the rare intraventricular cavernomas, purely intra-aqueductal
      cavernomas are exceptionally rare. CASE DESCRIPTION: A 62-year-old patient
      presented with progressive headache, memory loss, gait instability, and urinary
      incontinence. Magnetic resonance imaging showed the presence of a mass lesion
      located in the lumen of the cerebral aqueduct, associated with triventricular
      hydrocephalus. CONCLUSIONS: We discuss the rationale that led us to treat
      hydrocephalus with neuroendoscopy, which offered the possibility to directly
      inspect the intra-aqueductal lesion, make the diagnosis of cavernoma, and treat
      symptoms resulting from hydrocephalus without increasing the risk of bleeding.

PMID- 27890757
TI  - Percutaneous Endoscopic Removal of a Lumbar Epidural Angiolipoma via Interlaminar
      Approach: A Technical Report.
AB  - BACKGROUND: Although percutaneous endoscopic technique has been routinely used in
      the treatment of disk herniation, there are few reports on its application in the
      management of intraspinal tumors. We present a case report of lumbar epidural
      angiolipoma that was totally removed by percutaneous endoscopic technique. CASE
      DESCRIPTION: A 63-year-old man presented with a 4-month history of progressively
      worsening low back pain. No abnormal neurologic finding was noted on physical
      examination, and magnetic resonance imaging demonstrated a dorsally located L2-3
      epidural lesion, suggestive of a noninfiltrating angiolipoma. During the
      operation, an 8-mm skin incision was made, and a dilator was bluntly inserted
      toward the interlaminar space, followed by insertion of a working cannula onto
      the ligamentum flavum and placement of the endoscope. The interlaminar space was
      enlarged by resection of part of the lower rim of the right L2 vertebral laminae,
      and the right side of the interlaminar ligamentum flavum was removed to expose
      the tumor. The tumor was totally removed piecemeal under endoscopic guidance, and
      pathologic examination confirmed the diagnosis of angiolipoma. CONCLUSIONS: This
      report supports the application of percutaneous endoscopic technique in the
      surgical resection of noninfiltrating extradural lumbar angiolipoma.

PMID- 27890758
TI  - Surgical Outcome of Patients with Very Small Intracranial Aneurysms: A Single
      Center Experience from Southern Iran.
AB  - OBJECTIVES: To report the surgical outcome of very small intracranial aneurysms
      (VSIAs; <=3 mm) in a large referral neurovascular center in Southern Iran.
      METHODS: This cross-sectional study was conducted in Southern Iran during a 6
      year period between 2010 and 2016. We included all patients with VSIAs (<=3 mm)
      who underwent surgery in our center. All patients were operated on by a single
      neurosurgeon. Preoperative and postoperative computed tomography angiography and
      intraoperative imaging with indocyanine green video angiography were performed in
      all cases. The short-term and long-term outcome were determined by Glasgow Coma
      Scale (GCS) and modified Rankin Scale. RESULTS: A total of 62 VSIAs in 52
      patients were treated during the study period. There were no remnants and the
      complete occlusion rate was 100%. None of the patients experienced rebleeding.
      The 6-month mortality was 0% in unruptured VSIA, 3.8% in ruptured VSIA, and 5.7%
      in ruptured intracranial aneurysms other than VSIAs. Most patients had a
      favorable outcome (84.6%). An unfavorable outcome was associated with increased
      age (P = 0.027), higher rates of hypertension (P = 0.022) and ischemic heart
      disease (P = 0.023), lower GCS score on admission (P < 0.001), higher Hunt and
      Hess grade (P < 0.001), higher rate of preoperative ventriculoperitoneal shunt
      insertion (P = 0.040), and subarachnoid hemorrhage (P = 0.015). CONCLUSIONS:
      Surgical clipping of ruptured and unruptured VSIAs is a safe and effective
      modality of treatment associated with low mortality and morbidity. Age,
      comorbidities (hypertension, ischemic heart disease), GCS score on admission,
      Hunt and Hess grade, preoperative ventriculoperitoneal shunt insertion, and
      subarachnoid hemorrhage are important predictors of outcome in patients with
      VSIAs undergoing surgery.

PMID- 27890759
TI  - Transforaminal Percutaneous Endoscopic Lumbar Diskectomy with Percutaneous
      Epidural Neuroplasty in Lumbar Disk Herniation: Technical Note.
AB  - OBJECTIVE: Percutaneous endoscopic lumbar diskectomy and percutaneous epidural
      neuroplasty is a commonly used minimally invasive spinal surgery in lumbar disk
      herniation. But to our knowledge, there is no report about the results of
      percutaneous endoscopic lumbar diskectomy with percutaneous epidural neuroplasty.
      We did this study to evaluate the effect of percutaneous endoscopic lumbar
      diskectomy with percutaneous epidural neuroplasty in lumbar disk herniation.
      METHODS: We report a series of cases about techniques and results of percutaneous
      endoscopic lumbar diskectomy with percutaneous epidural neuroplasty in lumbar
      disk herniation, as well as introduce technical procedures and advantages.
      RESULTS: Seven patients improved axial back pain with percutaneous endoscopic
      lumbar diskectomy with percutaneous epidural neuroplasty and had no
      complications. The percutaneous endoscopic lumbar diskectomy with percutaneous
      epidural neuroplasty has many advantages with removing lumbar disk herniation in
      procedures. CONCLUSIONS: Percutaneous endoscopic lumbar diskectomy with
      percutaneous epidural neuroplasty is a safe and effective surgical method in
      lumbar disk herniation.

PMID- 27890760
TI  - Increased Short-Term Mortality in Patients with Spontaneous Intracerebral
      Hemorrhage and its Association with Admission Glucose Levels and Leukocytosis.
AB  - OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) can be a devastating event.
      An increased glucose level in patients with ICH is known to be related to poor
      outcomes, including acute leukocytosis, which is a well-established response to
      ICH. The purpose of this study was to evaluate the association between admission
      laboratory factors and 3-month mortality in patients with spontaneous
      supratentorial ICH. METHODS: We performed a Kaplan-Meier analysis to evaluate the
      risk factors for 3-month mortality in patients with ICH. We used univariate and
      multivariate Cox regression analyses to calculate hazard ratios with 95%
      confidence intervals for short-term mortality based on clinical and laboratory
      factors. The area under the receiver operating characteristic curve was used to
      determine the laboratory risk factors that predicted mortality. RESULTS: In
      total, 538 patients from our hospital admitted with primary spontaneous
      supratentorial ICH over an 8-year period were enrolled in this study. Higher
      leukocyte counts (hazard ratio, 1.019; 95% confidence interval, 1.012-1.027; P <
      0.001) and glucose levels on admission were associated with higher 3-month
      mortality. The receiver operating characteristic curve analysis showed that the
      areas under the curve of ICH volume, glucose, and leukocyte counts were 0.696
      (cutoff value, 41.63), 0.687 (cutoff value, 134), and 0.642 (cutoff value, 9.4),
      respectively. CONCLUSIONS: Higher admission white blood cell counts and glucose
      levels were associated with higher 3-month mortality in patients with spontaneous
      ICH. These data show that an altered glucose metabolism and inflammatory state
      after ICH may be related to early deterioration after an ICH.

PMID- 27890761
TI  - The Coexistence of Extradural Arteriovenous Fistula and Soft Tissue Arteriovenous
      Malformation Within the Same Metamere.
AB  - BACKGROUND: Spinal arteriovenous shunts are a common spinal vascular disorder.
      However, they can have a misleading clinical presentation and poor prognosis.
      They are classified into 4 types according to shunt points and drainage route,
      among which extradural arteriovenous fistula (eAVF) is the most rare, comprising
      only 1% of all spinal arteriovenous shunts. We report an extremely rare case of
      coexistent eAVF at the craniocervical junction and soft tissue arteriovenous
      malformation within the same metamere. CASE DESCRIPTION: A 30-year-old man
      presented with neck pain. T2-weighted magnetic resonance imaging revealed a flow
      void at the right craniocervical junction compressing the spinal cord.
      Angiography revealed eAVF at the craniocervical junction. The patient was treated
      via transvenous embolization. After the procedure, shunt flow and symptoms
      markedly decreased. During the operation, an extracranial arteriovenous
      malformation under the occipital skin was detected immediately after occluding
      the shunt point. CONCLUSIONS: This case indicates that transvenous embolization
      can be an effective treatment for eAVF and supports some hypotheses of
      arteriovenous malformation development. Additionally, it emphasizes the
      importance of examining a lesion with multiple modalities, including angiography,
      three-dimensional angiography, and cone-beam computed tomography, to understand
      the anatomy of the lesion.

PMID- 27890762
TI  - The Clinical Value of Intraoperative Mobile Computed Tomography in Managing High
      Risk Surgical Patients with Traumatic Brain Injury-A Single Tertiary Trauma
      Center Experience.
AB  - OBJECTIVE: A subset of surgically treated patients with traumatic brain injury
      (TBI) cannot be stabilized by initial surgery. Mobile computed tomography (CT)
      provides real-time information for diagnosis in these TBI surgically high-risk
      (TBI-SHR) patients. The objective of this study was to analyze a 5-year series of
      TBI-SHR patients to evaluate the impact of intraoperative mobile CT (imCT) on
      prognosis. METHODS: Of 1017 surgically treated patients with TBI retrospectively
      reviewed over a 5-year period (2009-2013), 59 patients required second operations
      within 72 hours of their initial surgery because of progressive or delayed
      hematomas (TBI-SHR group). Their clinical, radiographic, and intraoperative
      findings were compared among 19 patients who received imCT versus 40 patients who
      received fixed-unit CT. RESULTS: Our TBI-SHR group accounted for 5.8% of all
      surgically treated patients with TBI. The use of imCT led to a change in surgical
      plan in 56% of patients with TBI intraoperatively. Younger patients (<=55 years;
      P < 0.05) with multifocal hemorrhage on preoperative CT (P = 0.033) and with an
      intraoperative unexpected event such as intraoperative intracranial pressure >20
      mm Hg or acute brain swelling after adequate decompression (P = 0.003 and 0.004,
      respectively) significantly benefited from imCT in the TBI-SHR group. imCT also
      provided a quicker diagnosis (P < 0.001), led to a trend toward shorter intensive
      care unit stays (P = 0.077), and was associated with better neurologic outcomes
      at discharge days (P = 0.044). CONCLUSIONS: The use of imCT is associated with
      better neurologic outcomes at discharge days compared with the use of fixed-unit
      CT in TBI-SHR patients.

PMID- 27890763
TI  - Positional Occlusion of Vertebral Artery Due to Cervical Spondylosis as Rare
      Cause of Wake-up Stroke: Report of Two Cases.
AB  - BACKGROUND: Positional compression of the vertebral artery (VA) owing to cervical
      spondylosis is an uncommon cause of stroke. We report two cases of cervical
      spondylosis causing wake-up stroke, which is extremely rare. CASE DESCRIPTION:
      The first patient was a 78-year-old woman with vertigo and vomiting lasting from
      waking up. Magnetic resonance imaging (MRI) and angiography documented right
      cerebellar infarction, and stenosis of the right cervical VA. Dynamic angiography
      revealed that the right VA was occluded when her neck was extended or rotated to
      the right. Computed tomography (CT) angiography revealed the right VA compression
      by the right C5 superior articular process osteophytes. The second patient was a
      77-year-old man with dysarthria from waking up. MRI and angiography revealed
      right cerebellar infarction associated with the right VA stenosis and the left VA
      occlusion at C5-C6, whose cause was diagnosed as compression caused by bilateral
      uncovertebral osteophytes on CT angiography. Dynamic angiography showed that neck
      rotation to the right aggravated the right VA stenosis while recanalizing the
      left VA. Both patients were treated with a free radical scavenger (edaravone) and
      heparin, and underwent surgical decompression of VAs 14 or 18 days after onset.
      No recurrent ischemic events occurred thereafter. CONCLUSIONS: Magnetic resonance
      angiography of extracranial cervical VAs may be useful as an initial screening
      test for VA compression secondary to cervical spondylosis as a rare cause of wake
      up stroke, especially in cases of cerebral infarction in the posterior
      circulation with no evidences of causative arrhythmia and intracranial lesions.

PMID- 27890764
TI  - Spontaneous Spinal Epidural Hematoma: A Study of 55 Cases Focused on the Etiology
      and Treatment Strategy.
AB  - BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a rare neurologic
      emergency of the spinal cord. Its cause and treatment strategy remain
      controversial. This study aimed to evaluate a significant cause of SSEH and to
      discuss the treatment strategy according to the clinical outcomes of patients in
      2 institutions. METHODS: Fifty-five cases of SSEH treated at our institutions
      between February 2002 and February 2016 were retrospectively analyzed. RESULTS:
      The mean age of the first SSEH onset was 31.8 years. The follow-up rate was
      72.7%, with 28 patients (70%) showing satisfactory clinical outcomes. Forty
      patients received preoperative spinal digital subtraction angiography. Spinal
      epidural (extradural) arteriovenous fistula was detected in 6 patients (15%), 5
      of whom showed 1 type of special slow-flow shunt. Nineteen patients (34.5%)
      suffered from multiple episodes until they underwent invasive treatments or last
      follow-up. Rebleeding was confirmed in 8 patients. None of the patients had a
      subsequent episode or rebleeding after invasive treatment. The risk factors for
      poor clinical outcome included advanced age at initial onset (P = 0.020), a short
      progression interval (P = 0.030), no symptom relief after admission (P = 0.011),
      hypesthesia (P = 0.017), complete spinal cord injury (P = 0.001), and hematoma
      below the T4 level (P = 0.014). CONCLUSIONS: Spinal epidural (extradural)
      arteriovenous fistula is a significant cause of SSEH. Standard spinal digital
      subtraction angiography is necessary for patients with SSEH. Conservative
      treatment could not prevent occurrence of multiple episodes or rebleeding in
      patients. Microsurgery should be recommended as the preferred treatment strategy
      for SSEH. Endovascular embolization is also recommended if applicable.

PMID- 27890765
TI  - Revascularization of Moyamoya Angiopathy in Older Adults.
AB  - BACKGROUND: Moyamoya angiopathy most often manifests in patients in the second
      and third decades of life. Although uncommon, it can also manifest later in life.
      We present our results in patients >50 years old with moyamoya angiopathy who
      were treated with surgical revascularization via either direct bypass or indirect
      bypass (encephaloduroarteriosynangiosis). METHODS: A retrospective review was
      conducted to identify patients with moyamoya disease who were treated with
      surgical revascularization at our institution between 2002 and 2015. Outcomes and
      complications were analyzed. RESULTS: We identified 33 patients with moyamoya
      angiopathy >50 years old (mean age 59.0 years +/- 7.6) who were treated with
      surgical revascularization of 45 affected hemispheres. Of the affected
      hemispheres, 27 (60%) were treated with indirect bypasses and 18 (40%) were
      treated with direct bypasses. Neurologic complications occurred in 4 (12%)
      patients. The mean length of follow-up was 18.7 months +/- 18.6; 4 patients were
      lost to follow-up. At last follow-up, 11 of 18 (61%) direct bypasses were patent.
      Treatment failed in 5 of 45 (11%) treated hemispheres (stroke in 2 and persistent
      transient ischemic attacks in 3). In terms of functional outcome at last follow
      up, 16 of 29 (55%) patients were the same as before surgery, 10 (35%) were
      better, and 3 (10%) were worse (including 1 death). CONCLUSIONS: Although
      uncommon, moyamoya angiopathy can manifest in older adults. Surgical
      revascularization is a reasonable treatment option with good functional outcomes
      and an acceptable complication rate.

PMID- 27890766
TI  - United States Medical Licensing Examination Step 1 Scores Directly Correlate with
      American Board of Neurological Surgery Scores: A Single-Institution Experience.
AB  - BACKGROUND: Neurosurgery residency is becoming an increasingly competitive match.
      The process of screening and ranking applicants is a multifactorial process that
      lacks uniformity across residency programs. A significant factor is the
      applicant's performance on the United States Medical Licensing Examination
      (USMLE) Step 1. USMLE Step 1 scores are often used to project future success in
      residency and performance on specialty boards like the American Board of
      Neurological Surgery (ABNS) examination. The authors of this study investigate
      the strength of correlations between USMLE Step 1 and ABNS scores. METHODS: Data
      were extracted from records of graduating residents from the neurosurgery
      residency program at the University of California, Los Angeles, between 2003 and
      2010. Twenty-one residents were selected. USMLE Step 1 scores were deidentified
      and paired with ABNS scores. Correlation and regression analyses were performed.
      RESULTS: Higher USMLE Step 1 scores significantly correlated with higher ABNS
      scores (P = 0.01; Spearman correlation coefficient, 0.7). CONCLUSIONS: USMLE Step
      1 and ABNS scores are directly correlated. USMLE Step 1 scores will continue to
      be a valuable measure of projected success on ABNS written examinations, but more
      sophisticated measures are needed.

PMID- 27890767
TI  - Implications of Vestibular Schwannoma Consistency: Analysis of 140 Cases
      Regarding Radiologic and Clinical Features.
AB  - OBJECTIVE: To evaluate the effects of vestibular schwannoma (VS) consistency on
      internal auditory canal (IAC) widening, magnetic resonance imaging appearance,
      presenting symptoms, and facial nerve outcome. MATERIAL AND METHODS: We performed
      a retrospective analysis of 140 consecutive patients presenting with unilateral
      VS who underwent surgical treatment at the Department of Neurosurgery, Tuebingen
      University, Germany. Operative videos were analyzed, and the tumors were
      classified into soft and firm according to resectability with an ultrasonic
      aspirator at 40% power. IAC opening was measured in preoperative bone-window
      computed tomography on the pathologic and healthy sides, and the percentage of
      widening between both sides was calculated. Tumor signal intensity was assessed
      on T2-weighted magnetic resonance imaging scans. Preoperative and postoperative
      findings in the patient reports were documented. RESULTS: Widening of the IAC due
      to presence of the VS occurred in 118 patients (84.3%). The degree of IAC
      widening on the tumor side compared to the other side ranged from 0.1 to 10.1 mm
      (mean 2.6 mm). The mean widening of the IAC in relation to the healthy side was
      1.9 mm in soft tumors and 3.6 mm in firm tumors. A significant correlation was
      found between tumor consistency and degree of widening of the IAC (P < 0.0001).
      No significant correlation was found between tumor intensity (on T2-weighted
      imaging) and tumor consistency. In the early postoperative course, patients with
      soft tumors had better facial nerve function than those having firm tumors.
      However, at the last examination no difference between both groups was found.
      CONCLUSION: The consistency of VS has an impact on the immediate postoperative
      outcome. Widening on bony computed tomography scan, but not T2 intensity on
      magnetic resonance imaging, predicts whether the tumor is soft or firm.

PMID- 27890768
TI  - Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron
      Deficiency.
AB  - BACKGROUND & AIMS: Proton pump inhibitors (PPIs) and histamine-2 receptor
      antagonists (H2RAs) suppress gastric acid production, which can inhibit iron
      absorption. However, few data exist regarding whether these medications increase
      the risk of clinical iron deficiency. METHODS: A community-based case-control
      study evaluated the association between acid-suppressing medication use and the
      subsequent risk of iron deficiency. It contrasted 77,046 patients with new iron
      deficiency diagnoses (January 1999-December 2013), with 389,314 controls.
      Medication exposures, outcomes, and potential confounders used electronic
      databases. We excluded patients with pre-existing risk factors for iron
      deficiency. Associations were estimated using conditional logistic regression.
      RESULTS: Among cases, 2343 (3.0%) received a prior >=2-year supply of PPIs and
      1063 (1.4%) received H2RAs (without PPI use). Among controls, 3354 (0.9%)
      received a prior >=2-year supply of PPIs and 2247 (0.6%) H2RAs. Both >=2 years of
      PPIs (adjusted odds ratio, 2.49; 95% confidence interval, 2.35-2.64) and >=2
      years of H2RAs (odds ratio, 1.58; 95% CI, 1.46-1.71) were associated with an
      increased subsequent risk for iron deficiency. Among PPI users, the associations
      were stronger for higher daily doses (>1.5 vs <0.75 PPI pills/d; P value
      interaction = .004) and decreased after medication discontinuation (P-trend <
      .001). Some of the strongest associations were among persons taking >1.5 pills
      per day for at least 10 years (odds ratio, 4.27; 95% CI, 2.53-7.21). No similar
      strong associations were found for other commonly used prescription medications.
      CONCLUSIONS: Among patients without known risk factors for iron deficiency,
      gastric acid inhibitor use for >=2 years was associated with an increased
      subsequent risk of iron deficiency. The risk increased with increasing potency of
      acid inhibition and decreased after medication discontinuation.

PMID- 27890769
TI  - Real-Time Monitoring of Results During First Year of Dutch Colorectal Cancer
      Screening Program and Optimization by Altering Fecal Immunochemical Test Cut-Off
      Levels.
AB  - BACKGROUND & AIMS: After careful pilot studies and planning, the national
      screening program for colorectal cancer (CRC), with biennial fecal immunochemical
      tests (FITs), was initiated in The Netherlands in 2014. A national information
      system for real-time monitoring was developed to allow for timely evaluation.
      Data were collected from the first year of this screening program to determine
      the importance of planning and monitoring for optimal screening program
      performance. METHODS: The national information system of the CRC screening
      program kept track of the number of invitations sent in 2014, FIT kits returned,
      and colonoscopies performed. Age-adjusted rates of participation, the number of
      positive test results, and positive predictive values (PPVs) for advanced
      neoplasia were determined weekly, quarterly, and yearly. RESULTS: In 2014, there
      were 741,914 persons invited for FIT; of these, 529,056 (71.3%; 95% CI, 71.2%
      71.4%) participated. A few months into the program, real-time monitoring showed
      that rates of participation and positive test results (10.6%; 95% CI, 10.5%
      10.8%) were higher than predicted and the PPV was lower (42.1%; 95% CI, 41.3%
      42.9%) than predicted based on pilot studies. To reduce the burden of unnecessary
      colonoscopies and alleviate colonoscopy capacity, the cut-off level for a
      positive FIT result was increased from 15 to 47 MUg Hb/g feces halfway through
      2014. This adjustment decreased the percentage of positive test results to 6.7%
      (95% CI, 6.6%-6.8%) and increased the PPV to 49.1% (95% CI, 48.3%-49.9%). In
      total, the first year of the Dutch screening program resulted in the detection of
      2483 cancers and 12,030 advanced adenomas. CONCLUSIONS: Close monitoring of the
      implementation of the Dutch national CRC screening program allowed for instant
      adjustment of the FIT cut-off levels to optimize program performance.

PMID- 27890771
TI  - Echocardiographic Determinants of One-Year All-Cause Mortality in Patients With
      Chronic Heart Failure Complicated by Significant Functional Tricuspid
      Regurgitation.
AB  - BACKGROUND: Right ventricular (RV) dysfunction plays an important role in chronic
      heart failure (CHF). We evaluated the echocardiographic determinants of 1-year
      all-cause mortality in CHF patients with clinically relevant functional tricuspid
      regurgitation (TR). METHODS AND RESULTS: A total of 101 consecutive CHF patients
      (mean age 74 +/- 10 years, 53% male) with moderate or severe functional TR were
      enrolled. Each patient underwent at least 2 echocardiography examinations in an
      interval of >6 months. Clinical follow-up was made after a median of 305
      (interquartile range 164-365) days after the last echocardiography. The primary
      end point was all-cause mortality. Forty-two patients (42%) died during follow
      up. Baseline right atrial (RA) area, TR volume increase and RV enlargement over
      time were significantly higher in nonsurvivors than survivors (all P < .05).
      Compared to baseline levels, systolic pulmonary artery pressure (sPAP) was
      significantly reduced in nonsurvivors during follow-up echocardiography (54 +/-
      19 vs 49 +/- 21 mm Hg; P = .010), but significantly increased in survivors (48 +/
      17 vs 54 +/- 17 mm Hg; P = .001). Multivariable survival analysis suggested that
      baseline RA area >=27 cm2 (hazard ratio [HR] 2.41, 95% confidence interval [CI]
      1.21-4.80; P = .013), follow-up TR proximal isovelocity surface area regurgitant
      volume increase >=15 mL (HR 2.27, 95% CI 1.20-4.31; P = .012), RV middle diameter
      increase >=10 mm (HR 2.38, 95% CI 1.10-5.11; P = .027), and sPAP reduction >=10
      mm Hg (HR 3.04, 95% CI 1.51-6.13; P = .002) were determinants of 1-year all-cause
      mortality after the last echocardiography. Patients with 2 or 3 of these
      determinants were faced with significantly increased 1-year mortality (88% or
      100%). CONCLUSIONS: Dynamic RV morphologic and functional changes during serial
      echocardiography are associated with significantly increased mortality risk in
      CHF patients with moderate or severe functional TR.

PMID- 27890770
TI  - Fibrosis and Fibrotic Gene Expression in Pediatric and Adult Patients With
      Idiopathic Dilated Cardiomyopathy.
AB  - BACKGROUND: Although fibrosis seems to be prognostic for adverse outcomes in
      adults with idiopathic dilated cardiomyopathy (IDC), little is known about the
      prevalence and development of fibrosis in pediatric IDC hearts. We hypothesized
      that there is less activation of fibrosis at a molecular level in pediatric IDC
      hearts than in failing adult hearts. METHODS AND RESULTS: Pediatric hearts were
      analyzed histologically to determine the prevalence of fibrosis. Left ventricular
      tissue from adult and pediatric IDC hearts and adult and pediatric nonfailing
      (NF) hearts were subjected to quantitative reverse-transcription polymerase chain
      reaction to study the expression of important mRNAs that affect fibrosis. We
      found age-specific differences between IDC and NF hearts in the regulation of
      noncoding galectin-3, Corin, matrix metalloproteinase (MMP) 2, MMP-9, tissue
      inhibitor of metalloproteinase (TIMP) 2, and TIMP-3. We also found markers that
      were similarly altered in both adult and pediatric IDC hearts (interleukin-1
      receptor-like 1 receptor, TIMP-1, and TIMP-4). Finally, microRNAs 29a-c were
      significantly decreased in the pediatric IDC patients. CONCLUSIONS: Pediatric IDC
      patients demonstrate age-specific differences in the molecular pathways
      implicated in fibrosis in the adult heart. At the ultrastructural level the
      unique gene expression pattern appears to limit fibrosis in the failing pediatric
      heart.

PMID- 27890773
TI  - Primary photosensitization caused by ingestion of Froelichia humboldtiana by
      dairy goats.
AB  - This study aimed to describe the first report of an outbreak of primary
      photosensitization in dairy goats caused by Froelichia humboldtiana. The disease
      occurred from March to May 2014, in a mixed flock of 15 Saanen, Alpine, and
      crossbred lactating goats. The entire flock was affected; however, the Saanen and
      cross-bred goats developed more severe lesions, and their milk production
      decreased by as much as 75%. Lesions were progressive and consisted of skin
      hyperemia, edema, and necrosis, especially in depigmented areas. An experimental
      study with two goats resulted in photodermatitis, similar to that observed in the
      natural cases, 10-14 days after the beginning of plant ingestion. Serum
      activities of aspartate aminotransferase (AST) and -glutamyltransferase (GGT)
      and, direct, indirect, and total bilirubin serum concentrations were within the
      normal ranges. In conclusion, F. humboldtiana causes primary photosensitization
      in goats with a negative impact on milk production.

PMID- 27890772
TI  - Integrative analysis of DNA methylation and gene expression in butyrate-treated
      CHO cells.
AB  - The cellular mechanisms responsible for the versatile properties of CHO cells as
      the major production cell line for biopharmaceutical molecules are not entirely
      understood yet, although several 'omics' data facilitate the understanding of CHO
      cells and their reactions to environmental conditions. However, genome-wide
      studies of epigenetic processes such as DNA methylation are still limited. To
      prove the applicability and usefulness of integrating DNA methylation and gene
      expression data in a biotechnological context, we exemplarily analyzed the time
      course of cellular reactions upon butyrate addition in antibody-producing CHO
      cells by whole-genome bisulfite sequencing and CHO-specific cDNA microarrays.
      Gene expression and DNA methylation analyses showed that pathways known to be
      affected by butyrate, including cell cycle and apoptosis, as well as pathways
      potentially involved in butyrate-induced hyperproductivity such as central energy
      metabolism and protein biosynthesis were affected. Differentially methylated
      regions were furthermore found to contain binding-site motifs of specific
      transcription factors and were hypothesized to represent regulatory regions
      closely connected to the cellular response to butyrate. Generally, our experiment
      underlines the benefit of integrating DNA methylation and gene expression data,
      as it provided potential novel candidate genes for rational cell line development
      and allowed for new insights into the butyrate effect on CHO cells.

PMID- 27890774
TI  - Inhibition of local effects induced by Bothrops erythromelas snake venom:
      Assessment of the effectiveness of Brazilian polyvalent bothropic antivenom and
      aqueous leaf extract of Jatropha gossypiifolia.
AB  - Bothrops erythromelas is a snake of medical importance responsible for most of
      the venomous incidents in Northeastern Brazil. However, this species is not
      included in the pool of venoms that are used in the Brazilian polyvalent
      bothropic antivenom (BAv) production. Furthermore, it is well known that
      antivenom therapy has limited efficacy against venom-induced local effects,
      making the search for complementary alternatives to treat snakebites an important
      task. Jatropha gossypiifolia is a medicinal plant widely indicated in folk
      medicine as an antidote for snakebites, whose effectiveness against Bothrops
      jararaca venom (BjV) has been previously demonstrated in mice. In this context,
      this study assessed the effectiveness of the aqueous extract (AE) of this plant
      and of the BAv against local effects induced by B. erythromelas venom (BeV).
      Inhibition of BeV-induced edematogenic and hemorrhagic local effects was assayed
      in mice in pre-treatment (treatment prior to BeV injection) and post-treatment
      (treatment post-envenomation) protocols. Inhibition of proteolytic, phospholipase
      A2 (PLA2) and hyaluronidase enzymatic activities of BeV were evaluated in vitro.
      BAv cross-reactivity and estimation of antibody titers against BeV and BjV were
      assessed by Ouchterlony double diffusion test. The results show that in pre
      treatment protocol AE and BAv presented very similar effects (about 70% of
      inhibition for edematogenic and 40% for hemorrhagic activities). However, BAv
      poorly inhibited edema and hemorrhage in post-envenomation protocol, whilst, in
      contrast, AE was significantly active even when used after BeV injection. AE was
      able to inhibit all the tested enzymatic activities of BeV, while BAv was active
      only against hyaluronidase activity, which could justify the low effectiveness of
      BAv against BeV-induced local effects in vivo. Ouchterlony's test showed positive
      cross-reactivity against BeV, but the antibody titers were slightly higher
      against BjV. Together, these data indicate that despite the presence of
      immunological cross-reactivity, Brazilian polyvalent bothropic antivenom
      presented low inhibitory potential against biological and enzymatic effects of
      BeV, illustrating the need for new strategies in the production of antivenom with
      broad neutralizing potential in the treatment of Bothrops spp. envenomation
      throughout the country. Together, the results highlight the antiophidic potential
      of J. gossypiifolia, suggesting that it can be considered a potential adjuvant in
      the treatment of bothropic envenomation local effects.

PMID- 27890775
TI  - Expanding the neutralization scope of the EchiTAb-plus-ICP antivenom to include
      venoms of elapids from Southern Africa.
AB  - EchiTAb-plus-ICP is an antivenom prepared from plasma of horses hyperimmunized
      with the venoms of the carpet viper (Echis ocellatus), the puff adder (Bitis
      arietans) and the black-necked spitting cobra (Naja nigricollis). Therefore, the
      use of this antivenom has been limited to Western Africa. In order to expand the
      neutralization scope of EchiTAb-plus-ICP, we supplemented the immunogenic mixture
      with the venoms of B. arietans, the black mamba (Dendroaspis polylepis), the
      Mozambique spitting cobra (Naja mossambica), the snouted cobra (N. annulifera),
      and the rinkhals (Hemachatus haemachatus) from Swaziland. The ability of the
      expanded-scope antivenom, hereby named EchiTAb + ICP, to neutralize the venoms of
      B. arietans, D. polylepis, N. mossambica and H. haemachatus was similar to those
      of FAV Afrique and the SVA African antivenoms. In comparison to the SAIMR
      antivenom, the expanded-scope EchiTAb + ICP had lower ability to neutralize the
      venom of B. arietans, but similar ability to neutralize the venoms of D.
      polylepis, N. mossambica and H. haemachatus. Owing to its low protein
      concentration, the expanded-scope EchiTAb + ICP had lower ability to neutralize
      the venom of N. annulifera than FAV Afrique and the SAIMR antivenoms. However,
      when formulated at a protein concentration as high as FAV Afrique and SAIMR
      antivenoms, the expanded-scope EchiTAb + ICP showed similar capacity to
      neutralize this poorly immunogenic venom. Our results encourage the transition to
      the new EchiTAb + ICP antivenom, with an expanded neutralization scope that
      includes venoms of some of the most medically important elapids from Southern
      Africa. Clinical trials are required to determine the minimum effective-safe dose
      of the new EchiTAb + ICP for each type of envenomation.

PMID- 27890776
TI  - Epigallocatechin-3-gallate alleviates paraquat-induced acute lung injury and
      inhibits upregulation of toll-like receptors.
AB  - AIMS: To evaluate the detoxifying effect of epigallocatechin-3-gallate (EGCG) on
      paraquat (PQ)-induced acute lung injury in mice, and to explore the action
      mechanisms. MAIN METHODS: Following administration of PQ, the mice received a
      low, a medium or a high dose of EGCG daily for three days. Histopathology of the
      lungs were examined by H&E staining. The levels of inflammatory cytokines, such
      as TNF-alpha, IL-1beta and IL-6, in the bronchoalveolar lavage fluid were
      measured by enzyme-linked immunosorbent assay. Activation of NF-kappaB was
      assessed by Western blot and electrophoretic mobility gel shift assay. The
      expression of toll-like receptor (TLR)-2, 4, 9 and TLR adaptors (MyD88 and TRAF6)
      was detected by Western blot and immunohistochemical staining. The protective
      effect of EGCG against PQ toxicity was validated in vitro using A549 lung cancer
      cell line. KEY FINDINGS: Treatment with EGCG dose-dependently attenuated PQ
      induced acute lung injury in mice by reducing alveolar edema, hemorrhage,
      inflammatory cell infiltration and production of inflammatory cytokines. EGCG
      inhibited the activation of NF-kappaB and the upregulation of TLR 2, 4 and 9 as
      well as their adaptors MyD88 and TRAF6 in the lungs following PQ challenge. In
      addition, EGCG significantly reduced PQ-induced cell death, cytokine production,
      activation of NF-kappaB, and upregulation of TLRs and adaptors in A549 cells.
      SIGNIFICANCE: Our data suggest that TLR-mediated activation of NF-kappaB in the
      non-immune pulmonary cells could be involved in PQ-induced acute lung injury, and
      it may serve as a target of EGCG against PQ pulmonary toxicity.

PMID- 27890777
TI  - Psychological wellbeing in survivors of cardiac arrest, and its relationship to
      neurocognitive function.
AB  - OBJECTIVE: To characterise psychological wellbeing in survivors of out-of
      hospital cardiac arrest (OHCA), and examine its relationship to cognitive
      function. PATIENTS: Forty-one highly functioning cardiac arrest survivors were
      drawn from the follow-up cohort of a randomised controlled trial of initial
      airway management in OHCA (ISRCTN:18528625). DESIGN: Psychological wellbeing was
      assessed with a self-report questionnaire (the Depression Anxiety and Stress
      Scale; DASS) and cognitive function was examined using the Delayed Matching to
      Samples (DMS) test from the Cambridge Neuropsychological Test Automated Battery
      (CANTAB). RESULTS: Mean anxiety levels were significantly higher in this patient
      group than normative data drawn from the general population (p=0.046). Multiple
      regression analyses showed that cognitive function, measured by the DMS, did not
      predict any of the DASS scales. CONCLUSIONS: Anxiety plays an important role in
      determining perceived QoL in high functioning survivors, but psychological
      wellbeing is unrelated to cognitive function in this group. To achieve a
      comprehensive assessment of wellbeing, resuscitation research should consider
      outcomes beyond neurological function alone.

PMID- 27890778
TI  - Investigating the spatial specificity of S2-SSFP fMRI: A Monte Carlo simulation
      approach.
AB  - The desirable spatial specificity of spin echo (SE) fMRI cannot be efficiently
      utilized in high fields due to specific absorption rate (SAR) and B1
      inhomogeneity problems. Consequently, S2-SSFP fMRI has been suggested as an
      alternative to mitigate these problems. Nevertheless, no accurate analysis has
      been performed thus far to evaluate spatial specificity of this technique. To
      study spatial specificity, we performed Monte Carlo simulations for evaluating
      the micro-vasculature contribution in functional contrast along with vessel size
      sensitivity estimations for a range of relevant imaging parameters. Results
      showed a spatial specificity at the level of SE fMRI. Simulations further
      revealed that similar to SE fMRI, an effective echo time (TE) close to the tissue
      T2 maximizes the micro-vasculature contribution in the obtained contrast. The
      amount of this contribution, however, showed a slight decrease at ultra-high
      fields compared to SE fMRI. As for vessel size sensitivity, simulations presented
      a pattern for S2-SSFP similar to SE fMRI but with a minor shift toward larger
      vessels. These results are in general agreement with reported experimental
      studies. Our findings also suggest that the effect of older pathways, rather than
      primary SE pathway, might be responsible for the observed discrepancies between
      S2 and SE. Based on this study, provided that optimum experimental parameters are
      used, S2, with its desirable micro-vasculature contribution and high sensitivity
      to small vessels, is a promising low SAR approach to replace SE fMRI in high
      field.

PMID- 27890779
TI  - Fast triple-spin-echo Dixon (FTSED) sequence for water and fat imaging.
AB  - A number of 'Dixon' techniques based on fast spin echo (FSE) sequence have been
      proposed and successfully used in many branches of medicine. Some require only
      one scan, but most of them need multiple scans and long scan times. This article
      describes a new fast triple-spin-echo Dixon (FTSED) technique suitable for ultra
      high field MRI, in which three specific time shifts are introduced in the echo
      train; thus, three images with defined water-fat phase-differences (0, pi, 2pi)
      are encoded in the phase of the acquired images without extreme restrictions upon
      the echo duration. The water and fat images are then calculated by iterative
      least-squares estimation method. The sequence was successfully implemented at a
      9.4T ultra-high field MRI system and tested on a phantom and a rat.

PMID- 27890780
TI  - A Clinical Score to Predict Appendicitis in Older Male Children.
AB  - OBJECTIVE: To develop a clinical score to predict appendicitis among older, male
      children who present to the emergency department with suspected appendicitis.
      METHODS: Patients with suspected appendicitis were prospectively enrolled at 9
      pediatric emergency departments. A total of 2625 patients enrolled; a subset of
      961 male patients, age 8-18 were analyzed in this secondary analysis. Outcomes
      were determined using pathology, operative reports, and follow-up calls. Clinical
      and laboratory predictors with <10% missing data and kappa > 0.4 were entered
      into a multivariable model. Resultant beta-coefficients were used to develop a
      clinical score. Test performance was assessed by calculating the sensitivity,
      specificity, positive predictive value, negative predictive value, and likelihood
      ratios. RESULTS: The mean age was 12.2 years; 49.9% (480) had appendicitis, 22.3%
      (107) had perforation, and the negative appendectomy rate was 3%. In patients
      with and without appendicitis, overall imaging rates were 68.6% (329) and 84.4%
      (406), respectively. Variables retained in the model included maximum tenderness
      in the right lower quadrant, pain with walking/coughing or hopping, and the
      absolute neutrophil count. A score >=8.1 had a sensitivity of 25% (95% confidence
      interval [CI], 20%-29%), specificity of 98% (95% CI, 96%-99%), and positive
      predictive value of 93% (95% CI, 86%-97%) for ruling in appendicitis.
      CONCLUSIONS: We developed an accurate scoring system for predicting appendicitis
      in older boys. If validated, the score might allow clinicians to manage a
      proportion of male patients without diagnostic imaging.

PMID- 27890782
TI  - Bromodomain Histone Readers and Cancer.
AB  - Lysine acetylation of histone proteins is a fundamental post-translational
      modification that regulates chromatin structure and plays an important role in
      gene transcription. Aberrant levels of histone lysine acetylation are associated
      with the development of several diseases. Acetyl-lysine modifications create
      docking sites for bromodomains, which are structurally conserved modules present
      in transcription-associated proteins that are termed "reader" proteins.
      Bromodomain-containing reader proteins are part of multiprotein complexes that
      regulate transcription programs, which are often associated with profound
      phenotypic changes. Many bromodomain-containing proteins are aberrantly expressed
      in diseases, as best studied in cancers, where bromodomain proteins impact the
      expression of oncogenes and anti-apoptotic proteins. Thus, bromodomain readers of
      histone acetylation have emerged as attractive targets for cancer drug discovery,
      prompting immense interest in epigenetic-focused, medicinal chemistry to develop
      structurally guided chemical probes of bromodomains. Here, we describe
      bromodomain-containing proteins with defined roles in cancer and highlight recent
      progress in the development of bromodomain inhibitors.

PMID- 27890781
TI  - Promoting Early Brain and Child Development: Perceived Barriers and the
      Utilization of Resources to Address Them.
AB  - OBJECTIVE: Efforts to promote early brain and child development (EBCD) include
      initiatives to support healthy parent-child relationships, tools to identify
      family social-emotional risk factors, and referrals to community programs to
      address family risk factors. We sought to examine if pediatricians perceive
      barriers to implementing these activities, and if they utilize resources to
      address those barriers. METHODS: Data were analyzed from 304 nontrainee
      pediatricians who practice general pediatrics and completed a 2013 American
      Academy of Pediatrics Periodic Survey. Sample weights were used to decrease
      nonresponse bias. Bivariate comparisons and multivariable regression analyses
      were conducted. RESULTS: At least half of the pediatricians agreed that barriers
      to promoting EBCD include: a lack of tools to promote healthy parent-child
      relationships, a lack of tools to assess the family environment for social
      emotional risk factors, and a lack of local resources to address family risks.
      Endorsing a lack of tools to assess the family environment as a barrier was
      associated with using fewer screening tools and community resources. Endorsing a
      lack of local resources as a barrier was associated with using fewer community
      resources and fewer initiatives to promote parent-child relationships. Interest
      in pediatric mental health was associated with using more initiatives to promote
      healthy parent-child relationships, screening tools, and community resources.
      CONCLUSIONS: Although the majority of pediatricians perceive barriers to
      promoting EBCD, few are routinely using available resources to address these
      barriers. Addressing pediatricians' perceived barriers and encouraging interest
      in pediatric mental health may increase resource utilization and enhance efforts
      to promote EBCD.

PMID- 27890784
TI  - Identifying Residues that Determine SCF Molecular-Level Interactions through a
      Combination of Experimental and In silico Analyses.
AB  - The stem cell factor (SCF)/c-Kit receptor tyrosine kinase complex-with its
      significant roles in hematopoiesis and angiogenesis-is an attractive target for
      rational drug design. There is thus a need to map, in detail, the SCF/c-Kit
      interaction sites and the mechanisms that modulate this interaction. While most
      residues in the direct SCF/c-Kit binding interface can be identified from the
      existing crystal structure of the complex, other residues that affect binding
      through protein unfolding, intermolecular interactions, allosteric or long
      distance electrostatic effects cannot be directly inferred. Here, we describe an
      efficient method for protein-wide epitope mapping using yeast surface display. A
      library of single SCF mutants that span the SCF sequence was screened for
      decreased affinity to soluble c-Kit. Sequencing of selected clones allowed the
      identification of mutations that reduce SCF binding affinity to c-Kit. Moreover,
      the screening of these SCF clones for binding to a structural antibody helped
      identify mutations that result in small or large conformational changes in SCF.
      Computational modeling of the experimentally identified mutations showed that
      these mutations reduced the binding affinity through one of the three scenarios:
      through SCF destabilization, through elimination of favorable SCF/c-Kit
      intermolecular interactions, or through allosteric changes. Eight SCF variants
      were expressed and purified. Experimentally measured in vitro binding affinities
      of these mutants to c-Kit confirmed both the yeast surface display selection
      results and the computational predictions. This study has thus identified the
      residues crucial for c-Kit/SCF binding and has demonstrated the advantages of
      using a combination of computational and combinatorial methods for epitope
      mapping.

PMID- 27890785
TI  - Genomic Characterization of Dysplastic Nevi Unveils Implications for Diagnosis of
      Melanoma.
AB  - A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic
      nevus. These benign tumors represent clonal hyperproliferation of melanocytes
      that are in a senescent-like state, but with occasional malignant transformation
      events. To portray the mutational repertoire of dysplastic nevi in patients with
      the dysplastic nevus syndrome and to determine the discriminatory profiles of
      melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes
      of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted
      gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary
      melanomas (n = 42). Exome sequencing revealed that dysplastic nevi harbored a
      substantially lower mutational load than melanomas (21 protein-changing mutations
      versus >100). Known "driver" mutations in genes for melanoma, including CDKN2A,
      TP53, NF1, RAC1, and PTEN, were not found among any melanocytic nevi sequenced.
      Additionally, melanocytic nevi including dysplastic nevi showed a significantly
      lower frequency and a different UV-associated mutational signature. These results
      show that although melanocytic nevi and dysplastic nevi harbor stable genomes
      with relatively few alterations, progression into melanomas requires additional
      mutational processes affecting key tumor suppressors. This study identifies
      molecular parameters that could be useful for diagnostic platforms.

PMID- 27890783
TI  - The Proline/Glycine-Rich Region of the Biofilm Adhesion Protein Aap Forms an
      Extended Stalk that Resists Compaction.
AB  - Staphylococcus epidermidis is one of the primary bacterial species responsible
      for healthcare-associated infections. The most significant virulence factor for
      S. epidermidis is its ability to form a biofilm, which renders the bacteria
      highly resistant to host immune responses and antibiotic action. Intercellular
      adhesion within the biofilm is mediated by the accumulation-associated protein
      (Aap), a cell wall-anchored protein that self-assembles in a zinc-dependent
      manner. The C-terminal portion of Aap contains a 135-aa-long, proline/glycine
      rich region (PGR) that has not yet been characterized. The region contains a set
      of 18 nearly identical AEPGKP repeats. Analysis of the PGR using biophysical
      techniques demonstrated the region is a highly extended, intrinsically disordered
      polypeptide with unusually high polyproline type II helix propensity. In contrast
      to many intrinsically disordered polypeptides, there was a minimal temperature
      dependence of the global conformational state of PGR in solution as measured by
      analytical ultracentrifugation and dynamic light scattering. Furthermore, PGR was
      resistant to conformational collapse or alpha-helix formation upon the addition
      of the osmolyte trimethylamine N-oxide or the cosolvent 2,2,2-trifluoroethanol.
      Collectively, these results suggest PGR functions as a resilient, extended stalk
      that projects the rest of Aap outward from the bacterial cell wall, promoting
      intercellular adhesion between cells in the biofilm. This work sheds light on
      regions of low complexity often found near the attachment point of bacterial cell
      wall-anchored proteins.

PMID- 27890787
TI  - Inflammatory Linear Verrucous Epidermal Nevus with a Postzygotic GJA1 Mutation Is
      a Mosaic Erythrokeratodermia Variabilis et Progressiva.

PMID- 27890786
TI  - Heat Increases the Editing Efficiency of Human Papillomavirus E2 Gene by Inducing
      Upregulation of APOBEC3A and 3G.
AB  - Apolipoprotein B mRNA-editing catalytic polypeptide (APOBEC) 3 proteins have been
      identified as potent viral DNA mutators and have broad antiviral activity. In
      this study, we demonstrated that apolipoprotein B mRNA-editing catalytic
      polypeptide 3A (A3A) and A3G expression levels were significantly upregulated in
      human papillomavirus (HPV)-infected cell lines and tissues. Heat treatment
      resulted in elevated expression of A3A and A3G in a temperature-dependent manner
      in HPV-infected cells. Correspondingly, HPV-infected cells heat-treated at 44 
      degrees C showed accumulated G-to-A or C-to-T mutation in HPV E2 gene. Knockdown
      of A3A or A3G could promote cell viability, along with the lower frequency of A/T
      in HPV E2 gene. In addition, regressing genital viral warts also harbored high G
      to-A or C-to-T mutation in HPV E2 gene. Taken together, we demonstrate that
      apolipoprotein B mRNA-editing catalytic polypeptide 3 expression and editing
      function was heat sensitive to a certain degree, partly explaining the mechanism
      of action of local hyperthermia to treat viral warts.

PMID- 27890788
TI  - Genetic testing among Spanish pediatric neurologists: Knowledge, attitudes and
      practices.
AB  - Advances in genetic testing applied to child neurology have enabled the
      development of genetic tests with greater sensitivity in elucidating an etiologic
      diagnosis for common neurological conditions. The objective of the current study
      was to examine child neurologists' perspectives and insights into genetic
      testing. We surveyed 118 Spanish child neurologists, exploring their knowledge,
      attitudes, and practices concerning genetic tests. All of them had requested at
      least one genetic test in the past six months. Global developmental delay or
      intellectual disability in absence of a strong specific etiologic suspicion and
      autism spectrum disorders were the disorders for which genetic testing was most
      frequently requested. The most commonly requested genetic test was CGH-array.
      Overall, child neurologist perception of readiness for making genetic-related
      decisions was not bad, although many would like to have a greater support from
      geneticists and were interested in increasing the time dedicated to genetics
      within their continuing education program. These data have important implications
      for future practice, research, and education.

PMID- 27890789
TI  - Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with
      NTCP transporter activity.
AB  - BACKGROUND & AIMS: The sodium taurocholate co-transporting polypeptide (NTCP) is
      the main target of most hepatitis B virus (HBV) specific entry inhibitors.
      Unfortunately, these agents also block NTCP transport of bile acids into
      hepatocytes, and thus have the potential to cause adverse effects. We aimed to
      identify small molecules that inhibit HBV entry while maintaining NTCP
      transporter function. METHODS: We characterized a series of cyclosporine (CsA)
      derivatives for their anti-HBV activity and NTCP binding specificity using HepG2
      cells overexpressing NTCP and primary human hepatocytes. The four most potent
      derivatives were tested for their capacity to prevent HBV entry, but maintain
      NTCP transporter function. Their antiviral activity against different HBV
      genotypes was analysed. RESULTS: We identified several CsA derivatives that
      inhibited HBV infection with a sub-micromolar IC50. Among them, SCY446 and SCY450
      showed low activity against calcineurin (CN) and cyclophilins (CyPs), two major
      CsA cellular targets. This suggested that instead, these compounds interacted
      directly with NTCP to inhibit viral attachment to host cells, and have no
      immunosuppressive function. Importantly, we found that SCY450 and SCY995 did not
      impair the NTCP-dependent uptake of bile acids, and inhibited multiple HBV
      genotypes including a clinically relevant nucleoside analog-resistant HBV
      isolate. CONCLUSIONS: This is the first example of small molecule selective
      inhibition of HBV entry with no decrease in NTCP transporter activity. It
      suggests that the anti-HBV activity can be functionally separated from bile acid
      transport. These broadly active anti-HBV molecules are potential candidates for
      developing new drugs with fewer adverse effects. LAY SUMMARY: In this study, we
      identified new compounds that selectively inhibited hepatitis B virus (HBV)
      entry, and did not impair bile acid uptake. Our evidence offers a new strategy
      for developing anti-HBV drugs with fewer side effects.

PMID- 27890790
TI  - Efficacy and tolerability of an IFN-free regimen with DCV/ASV for elderly
      patients infected with HCV genotype 1B.
AB  - BACKGROUND & AIMS: Anti-hepatitis C virus (HCV) therapy by interferon (IFN)-free
      regimen with oral direct-acting antiviral drugs are tolerable in aged patients,
      with fewer adverse effects than IFN-based therapies. We investigated the efficacy
      and tolerability of an IFN-free anti-HCV therapy in extremely aged patients, as
      well as the survival benefit of sustained virologic response (SVR). METHODS:
      Following IFN-free therapy with daclatasvir and asunaprevir, tolerability and SVR
      rate were compared between 115 HCV genotype 1-infected patients aged 80years or
      older, 151 patients in their 70s (?70 and <80years), and 115 patients under the
      age of 70. One-year mortality and morbidity in patients aged ?80years were
      compared between SVR patients and propensity score-matched patients with
      persistent HCV infection. RESULTS: The SVR rate was 96.5% in patients ?80years,
      comparable to that in patients aged ?70 and <80years (95.4%) and patients aged
      <70years (93.9%). There were no differences in treatment discontinuation rate
      (2.6%, 1.3%, and 0.9%, respectively). One-year mortality was significantly lower
      in SVR patients (2.7%) than in patients with persistent HCV infection (15.3%,
      p=0.0016). Whereas 1-year mortality due to liver-related diseases was 8.1% in
      patients with persistent HCV infection who were aged ?80years, no SVR patients
      died from liver diseases within 1-year after the end of therapy. CONCLUSIONS: IFN
      free therapy for HCV infection was associated with high tolerability and
      antiviral efficacy, even in patients aged ?80years. In addition, there seemed to
      be a survival benefit from the eradication of HCV in this population. LAY
      SUMMARY: IFN-free therapy with oral direct-acting antiviral drugs (daclatasvir
      and asunaprevir) for HCV infection showed similar tolerability and antiviral
      efficacy in patients aged ?80years as in younger patients (patients aged ?70 and
      <80years and patients aged <70years), with an SVR rate over 90% and no severe
      adverse effects. There was a survival benefit from the eradication of HCV even in
      patients aged ?80years.

PMID- 27890791
TI  - Fecal microbiota manipulation prevents dysbiosis and alcohol-induced liver injury
      in mice.
AB  - BACKGROUND & AIMS: Alcoholic liver disease (ALD) is a leading cause of liver
      failure and mortality. In humans, severe alcoholic hepatitis is associated with
      key changes to intestinal microbiota (IM), which influences individual
      sensitivity to develop advanced ALD. We used the different susceptibility to ALD
      observed in two distinct animal facilities to test the efficiency of two
      complementary strategies (fecal microbiota transplantation and prebiotic
      treatment) to reverse dysbiosis and prevent ALD. METHODS: Mice were fed alcohol
      in two distinct animal facilities with a Lieber DeCarli diet. Fecal microbiota
      transplantation was performed with fresh feces from alcohol-resistant donor mice
      to alcohol-sensitive receiver mice three times a week. Another group of mice
      received pectin during the entire alcohol consumption period. RESULTS: Ethanol
      induced steatosis and liver inflammation, which were associated with disruption
      of gut homeostasis, in alcohol-sensitive, but not alcohol resistant mice. IM
      analysis showed that the proportion of Bacteroides was specifically lower in
      alcohol-sensitive mice (p<0.05). Principal coordinate analysis showed that the IM
      of sensitive and resistant mice clustered differently. We targeted IM using two
      different strategies to prevent alcohol-induced liver lesions: (1) pectin
      treatment which induced major modifications of the IM, (2) fecal microbiota
      transplantation which resulted in an IM very close to that of resistant donor
      mice in the sensitive recipient mice. Both methods prevented steatosis, liver
      inflammation, and restored gut homeostasis. CONCLUSIONS: Manipulation of IM can
      prevent alcohol-induced liver injury. The IM should be considered as a new
      therapeutic target in ALD. LAY SUMMARY: Sensitivity to alcoholic liver disease
      (ALD) is driven by intestinal microbiota in alcohol fed mice. Treatment of mice
      with alcohol-induced liver lesions by fecal transplant from alcohol fed mice
      resistant to ALD or with prebiotic (pectin) prevents ALD. These findings open new
      possibilities for treatment of human ALD through intestinal microbiota
      manipulation.

PMID- 27890792
TI  - Validating the ALBI grade: Its current and future use in HCC prognostication.

PMID- 27890793
TI  - Reply to: 'Validating the ALBI grade: Its current and future use in HCC
      prognostication'.

PMID- 27890794
TI  - Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of
      experimental multiple sclerosis.
AB  - This study was aimed to investigate whether treatment with purified cannabidiol
      (CBD) may counteract the development of experimental multiple sclerosis (MS), by
      targeting the PI3K/Akt/mTOR pathway. Although the PI3K/Akt/mTOR pathway was found
      to be activated by cannabinoids in several immune and non-immune cells,
      currently, there is no data about the effects of CBD in the PI3K/Akt/mTOR
      activity in MS. Experimental Autoimmune Encephalomyelitis (EAE), the most common
      model of MS, was induced in C57BL/6 mice by immunization with myelin
      oligodendroglial glycoprotein peptide (MOG)35-55. After EAE onset, which occurs
      approximately 14days after disease induction, mice were daily intraperitoneally
      treated with CBD (10mg/kg mouse) and observed for clinical signs of EAE. At
      28days from EAE-induction, mice were euthanized and spinal cord tissues were
      sampled to perform immunohistochemical evaluations and western blot analysis. Our
      results showed a clear downregulation of the PI3K/Akt/mTOR pathway following EAE
      induction. CBD treatment was able to restore it, increasing significantly the
      phosphorylation of PI3K, Akt and mTOR. Also, an increased level of BNDF in CBD
      treated mice seems to be involved in the activation of PI3K/Akt/mTOR pathway. In
      addition, our data demonstrated that therapeutic efficacy of CBD treatment is due
      to reduction of pro-inflammatory cytokines, like IFN-gamma and IL-17 together
      with an up-regulation of PPARgamma. Finally, CBD was found to promote neuronal
      survival by inhibiting JNK and p38 MAP kinases. These results provide an
      interesting discovery about the regulation of the PI3K/Akt/mTOR pathway by
      cannabidiol administration, that could be a new potential therapeutic target for
      MS management.

PMID- 27890795
TI  - Inhibition of histone/lysine acetyltransferase activity kills CoCl2-treated and
      hypoxia-exposed gastric cancer cells and reduces their invasiveness.
AB  - Hypoxia enhances immortality and metastatic properties of solid tumors.
      Deregulation of histone acetylation has been associated with several metastatic
      cancers but its effect on hypoxic responses of cancer cells is not known. This
      study aimed at understanding the effectiveness of the hydrazinocurcumin, CTK7A,
      an inhibitor of p300 lysine/histone acetyltransferase (KAT/HAT) activity, in
      inducing apoptosis of gastric cancer cells (GCCs) exposed to cobalt chloride
      (CoCl2), a hypoxia-mimetic chemical, or 1% O2. Here, we show that CTK7A-induced
      hydrogen peroxide (H2O2) generation in CoCl2-exposed and invasive gastric cancer
      cells (GCCs) leads to p38 MAPK-mediated Noxa expression and thereafter,
      mitochondrial apoptotic events. Noxa induction in normal immortalized gastric
      epithelial cells after CTK7A and hypoxia-exposure is remarkably less in
      comparison to similarly-treated GCCs. Moreover, hypoxia-exposed GCCs, which have
      acquired invasive properties, become apoptotic after CTK7A treatment to a
      significantly higher extent than normoxic cells. Thus, we show the potential of
      CTK7A in sensitizing hypoxic and metastatic GCCs to apoptosis induction.

PMID- 27890797
TI  - 3-Bromopyruvate treatment induces alterations of metabolic and stress-related
      pathways in glioblastoma cells.
AB  - : Glioblastoma (GBM) is the most common and aggressive brain tumour of adults.
      The metabolic phenotype of GBM cells is highly dependent on glycolysis;
      therefore, therapeutic strategies aimed at interfering with glycolytic pathways
      are under consideration. 3-Bromopyruvate (3BP) is a potent antiglycolytic agent,
      with a variety of targets and possible effects on global cell metabolism. Here we
      analyzed the changes in protein expression on a GBM cell line (GL15 cells) caused
      by 3BP treatment using a global proteomic approach. Validation of differential
      protein expression was performed with immunoblotting and enzyme activity assays
      in GL15 and U251 cell lines. The results show that treatment of GL15 cells with
      3BP leads to extensive changes in the expression of glycolytic enzymes and stress
      related proteins. Importantly, other metabolisms were also affected, including
      pentose phosphate pathway, aminoacid synthesis, and glucose derivatives
      production. 3BP elicited the activation of stress response proteins, as shown by
      the phosphorylation of HSPB1 at serine 82, caused by the concomitant activation
      of the p38 pathway. Our results show that inhibition of glycolysis in GL15 cells
      by 3BP influences different but interconnected pathways. Proteome analysis may
      help in the molecular characterization of the glioblastoma response induced by
      pharmacological treatment with antiglycolytic agents. SIGNIFICANCE: Alteration of
      the glycolytic pathway characterizes glioblastoma (GBM), one of the most common
      brain tumours. Metabolic reprogramming with agents able to inhibit carbohydrate
      metabolism might be a viable strategy to complement the treatment of these
      tumours. The antiglycolytic agent 3-bromopyruvate (3BP) is able to strongly
      inhibit glycolysis but it may affect also other cellular pathways and its precise
      cellular targets are currently unknown. To understand the protein expression
      changes induced by 3BP, we performed a global proteomic analysis of a GBM cell
      line (GL15) treated with 3BP. We found that 3BP affected not only the glycolytic
      pathway, but also pathways sharing metabolic intermediates with glycolysis, such
      as the pentose phosphate pathway and aminoacid metabolism. Furthermore, changes
      in the expression of proteins linked to resistance to cell death and stress
      response were found. Our work is the first analysis on a global scale of the
      proteome changes induced by 3BP in a GBM model and may contribute to clarifying
      the anticancer potential of this drug.

PMID- 27890796
TI  - Temporal profiles of plasma proteome during childhood development.
AB  - Human blood plasma proteome reflects physiological changes associated with a
      child's development as well as development of disease states. While age-specific
      normative values are available for proteins routinely measured in clinical
      practice, there is paucity of comprehensive longitudinal data regarding changes
      in human plasma proteome during childhood. We applied TMT-10plex isobaric
      labeling-based quantitative proteomics to longitudinally profile the plasma
      proteome in 10 healthy children during their development, each with 9 serial time
      points from 9months to 15years of age. In total, 1828 protein groups were
      identified at peptide and protein level false discovery rate of 1% and with at
      least two razor and unique peptides. The longitudinal expression profiles of 1747
      protein groups were statistically modeled and their temporal changes were
      categorized into 7 different patterns. The patterns and relative abundance of
      proteins obtained by LC-MS were also verified with ELISA. To our knowledge, this
      study represents the most comprehensive longitudinal profiling of human plasma
      proteome to date. The temporal profiles of plasma proteome obtained in this study
      provide a comprehensive resource and reference for biomarker studies in childhood
      diseases. Biological significance: A pediatric plasma proteome database with
      longitudinal expression patterns of 1747 proteins from neonate to adolescence was
      provided to the research community. 970 plasma proteins had age-dependent
      expression trends, which demonstrated the importance of longitudinal profiling
      study to identify the potential biomarkers specific to childhood diseases, and
      the requirement of strictly age-matched clinical samples in a cross-sectional
      study in pediatric population.

PMID- 27890798
TI  - Performance of the subcutaneous implantable cardioverter-defibrillator in
      patients with a primary prevention indication with and without a reduced ejection
      fraction versus patients with a secondary prevention indication.
AB  - BACKGROUND: The subcutaneous implantable defibrillator (S-ICD) provides an
      alternative to the transvenous ICD for the prevention of sudden cardiac death,
      but has not been well studied in the most commonly treated transvenous ICD
      patient population, namely, primary prevention (PP) patients with left
      ventricular dysfunction. OBJECTIVE: The analyses in the present study were
      designed to compare clinical outcomes for PP patients with and without a reduced
      ejection fraction (EF) and secondary prevention (SP) patients implanted with the
      S-ICD. METHODS: All patients 18 years and older from the S-ICD IDE study and the
      EFFORTLESS Registry with available data as of November 18, 2013, were included (n
      = 856; mean follow-up duration 644 days). Outcomes were evaluated in 2 analyses:
      (1) comparing all PP patients (n = 603, 70.4%) with all SP patients (n = 253,
      29.6%) and (2) comparing all PP patients with an EF <=35% (n = 379) with those
      with an EF >35% (n = 149, 17.4%). RESULTS: No differences were observed in
      mortality, complications, inappropriate therapy, or ability to convert
      ventricular tachyarrhythmias between SP and PP patients. However, SP patients had
      a higher incidence of appropriate therapy than did PP patients (11.9% vs 5.0%; P
      = .0004). In the PP subanalysis, the cohort with an EF <=35% had significantly
      older patients with more comorbidities and higher mortality (3.0% annually vs
      0.0%). Despite these differences, device-related complications, conversion
      efficacy, and incidence of inappropriate shock therapies were not significantly
      different between PP subgroups. CONCLUSION: The S-ICD performs well in protecting
      patients with either PP or SP implant indications from sudden cardiac death.
      Within PP patients, device performance was independent of EF.

PMID- 27890799
TI  - Enhancing gilthead seabream immune status and protection against bacterial
      challenge by means of antigens derived from Vibrio parahaemolyticus.
AB  - In an attempt to control the proliferation of the pathogenic bacterium Vibrio
      parahaemolyticus in gilthead seabream (Sparus aurata), the immunostimulant effect
      of lysate and ToxA from this bacterium was evaluated. Fish were intraperitoneally
      injected twice (first injection, day 1 of the experiment; second injection, day
      7) and sampled after one week (on days 8 and 15). Afterwards, all fish specimens
      were experimentally infected with V. parahaemolyticus and mortality was recovered
      for 1 week. Fish injected with lysate, ToxA and phosphate buffer saline (control)
      showed 100%, 50% and 0% survival, respectively, when challenged with the
      pathogen. Skin mucus immune parameters and immune-related gene expression in skin
      and spleen were also evaluated. The results showed that mucus immune parameters
      were enhanced in the lysate and ToxA groups compared with the values obtained for
      fish from the control group. Expression of IL-1beta, TNF-alpha, C3 and IgM genes
      was significantly up-regulated in the lysate and ToxA groups, principally after
      infection with the bacterium. Interestingly, TLR5 gene expression increased in
      fish immunized with lysate. The most prominent histological characteristic in gut
      from infected fish was the presence of a great number of intraepithelial
      leucocytes as well as inflammation of the submucosa, while severe hydropic
      degeneration and hemosiderosis were detected in liver from infected fish.
      Injection of lysate or ToxA had a protective effect against the deleterious
      consequences of subsequent infection with V. parahaemolyticus in gut and liver.
      The findings underline the potential of lysate and ToxA as potent preventive
      antigens against this kind of vibriosis.

PMID- 27890800
TI  - Metabolic responses of Haliotis diversicolor to Vibrio parahaemolyticus
      infection.
AB  - Vibrio parahemolyticus is a devastating bacterial pathogen that often causes
      outbreak of vibriosis in abalone Haliotis diversicolor. Elucidation of metabolic
      mechanisms of abalones in responding to V. parahemolyticus infection is essential
      for controlling the epidemic. In this work, 1H NMR-based metabolomic techniques
      along with correlation and network analyses are used to investigate
      characteristic metabolites, as well as corresponding disturbed pathways in
      hepatopancreas and gill of H. diversicolor after V. parahemolyticus infection for
      48 h. Results indicate that obvious gender- and tissue-specific metabolic
      responses are induced. Metabolic responses in female abalones are more clearly
      observed than those in males, which are primarily manifested in the accumulation
      of branched-chain amino acids and the depletion of organic osmolytes (homarine,
      betaine and taurine) in the infected gills of female abalones, as well as in the
      depletion of glutamate, branched-chain and aromatic amino acids in the infected
      hepatopancreases of female abalones. Moreover, based on major metabolic functions
      of the characteristic metabolites, we have found that V. parahemolyticus
      infection not only cause the disturbance in energy metabolism, nucleotide
      metabolism and osmotic balance, but also induce oxidative stress, immune stress
      and neurotoxic effect in different tissues with various mechanisms. Our study
      provides details of metabolic responses of abalones to V. parahemolyticus
      infection and will shed light on biochemical defence mechanisms of male and
      female hosts against pathogen infection.

PMID- 27890801
TI  - EUS-guided paclitaxel injection as an adjunctive therapy to systemic chemotherapy
      and concurrent external beam radiation before surgery for localized or
      locoregional esophageal cancer: a multicenter prospective randomized trial.
AB  - BACKGROUND AND AIMS: OncoGel (Protherics Salt Lake City, Inc, Salt Lake City, UT)
      is paclitaxel (PTX) formulated in a thermosensitive, biodegradable copolymer for
      focused cytotoxicity and radiosensitization. A phase 2a study suggested that EUS
      guided PTX injection into esophageal tumors subsequently receiving radiotherapy
      was safe. METHODS: In an international multicenter, prospective, randomized phase
      2b study, patients with local or locoregional adenocarcinoma or squamous cell
      carcinoma (SCC) of the esophagus/gastroesophageal junction and eligible for
      neoadjuvant chemoradiotherapy (CRT) before surgery were randomized to standard of
      care (SOC) plus EUS-guided PTX injection or SOC alone. PTX was injected in 0.5 to
      1.0 mL aliquots throughout the tumor. Planned CRT as SOC was intravenous 5
      fluorouracil for the first 4 days (weeks 1 and 5), intravenous cisplatin on the
      first day of each 5-fluorouracil course, and radiotherapy over 5.5 weeks.
      Patients were evaluated weekly during CRT and re-evaluated at 12 weeks for
      surgical eligibility and CT for change in overall tumor volume. RESULTS: The
      analysis included 137 patients (97 males; mean age, 58 +/- 9.1 years) randomized
      to PTX + SOC (n = 72) and SOC (n = 65) by using a modified intention-to-treat
      approach. Overall response by tumor volume between the PTX (12.5%) and the SOC
      group (20.0%; P = .24; odds ratio, 0.57; 95% confidence interval, 0.23-1.44) was
      similar. Pathologic complete response was higher in the SOC group (26.2% vs
      12.5%; P = .046); however, 12-month survival (P = .412) and the overall frequency
      of 1 or more adverse events (P = .17) were similar between the 2 groups.
      CONCLUSIONS: SOC + PTX is safe but does not improve overall survival or overall
      tumor response at the primary tumor site for patients with local or locoregional
      cancer of the esophagus/gastroesophageal junction. (Clinical trial registration
      number: NCT00573131.).

PMID- 27890802
TI  - Highly water-absorbing silk yarn with interpenetrating network via in situ
      polymerization.
AB  - Silk was modified via in situ polymerization of two monomers acrylamide and
      sodium acrylate by swelling in an effective LiBr dissolution system. Swelling of
      natural silks in LiBr solutions of low concentration was clearly observed under
      optical microscope, and their conformational changes were revealed by X-ray
      diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Dissolution
      tests and FTIR spectra of these modified silks suggested the presence of
      interpenetrating network of polyacrylamide and poly(sodium acrylate) in the silk
      yarns. These modified silks exhibited superior water absorption to that of raw
      silk and greatly improved mechanical properties in both dry and wet states. These
      novel modified silks also showed low cytotoxicity towards skin keratinocytes,
      having potential applications in biomedical textiles. This modification method by
      in situ polymerization after swelling in LiBr provides a new route to highly
      enhance the properties and performance of silk for various applications.

PMID- 27890803
TI  - Neural signatures of phonological deficits in Chinese developmental dyslexia.
AB  - There has been debate on whether phonological deficits explain reading difficulty
      in Chinese, since Chinese is a logographic language which does not employ
      grapheme-phoneme-correspondence rules and remote memorization seems to be the
      main method to acquire reading. In the current study, we present neuroimaging
      evidence that the phonological deficit is also a signature of Chinese dyslexia.
      Specifically, we found that Chinese children with dyslexia (DD) showed reduced
      brain activation in the left dorsal inferior frontal gyrus (dIFG) when compared
      to both age-matched controls (AC) and reading-matched controls (RC) during an
      auditory rhyming judgment task. This suggests that the phonological processing
      deficit in this region may be a signature of dyslexia in Chinese, rather than a
      difference due to task performance or reading ability, which was matched on DD
      and RC. At exactly the same region of the left dIFG, we found a positive
      correlation between brain activation and reading skill in DD, suggesting that the
      phonological deficit is associated with the severity of dyslexia. We also found
      increased brain activation in the right precentral gyrus in DD than both AC and
      RC, suggesting a compensation of reliance on articulation. Functional
      connectivity analyses revealed that DD had a weaker connection between the left
      superior temporal gyrus (STG) and fusiform gyrus (FG) than the two control
      groups, suggesting that the reduced connection between phonology and orthography
      is another neural signature of dyslexia. In contrast, DD showed greater
      connectivity between the left dIFG and the left inferior parietal lobule (IPL)
      than both control groups, suggesting a reduced segregation between the language
      network and default mode network in dyslexic children. We also found that
      connectivity between the left STG and the left dIFG was sensitive to task
      performance and/or reading skill rather than being dyslexic or not, because AC
      was greater than both RC and DD, while the connectivity between the left middle
      occipital gyrus (MOG) and left STG was sensitive to age, because both AC and DD
      were greater than RC. In summary, our study provides the very first neurological
      evidence of phonological deficits in Chinese developmental dyslexia and we
      successfully distinguished variations of brain activity/functional connectivity
      due to age, performance, and dyslexia by comparing AC, RC, and DD.

PMID- 27890805
TI  - Predicting brain-age from multimodal imaging data captures cognitive impairment.
AB  - The disparity between the chronological age of an individual and their brain-age
      measured based on biological information has the potential to offer clinically
      relevant biomarkers of neurological syndromes that emerge late in the lifespan.
      While prior brain-age prediction studies have relied exclusively on either
      structural or functional brain data, here we investigate how multimodal brain
      imaging data improves age prediction. Using cortical anatomy and whole-brain
      functional connectivity on a large adult lifespan sample (N=2354, age 19-82), we
      found that multimodal data improves brain-based age prediction, resulting in a
      mean absolute prediction error of 4.29 years. Furthermore, we found that the
      discrepancy between predicted age and chronological age captures cognitive
      impairment. Importantly, the brain-age measure was robust to confounding effects:
      head motion did not drive brain-based age prediction and our models generalized
      reasonably to an independent dataset acquired at a different site (N=475).
      Generalization performance was increased by training models on a larger and more
      heterogeneous dataset. The robustness of multimodal brain-age prediction to
      confounds, generalizability across sites, and sensitivity to clinically-relevant
      impairments, suggests promising future application to the early prediction of
      neurocognitive disorders.

PMID- 27890806
TI  - The endocrine disrupting potential of monosodium glutamate (MSG) on secretion of
      the glucagon-like peptide-1 (GLP-1) gut hormone and GLP-1 receptor interaction.
AB  - Monosodium glutamate (MSG) is a suspected obesogen with epidemiological evidence
      positively correlating consumption to increased body mass index and higher
      prevalence of metabolic syndrome. ELISA and high content analysis (HCA) were
      employed to examine the disruptive effects of MSG on the secretion of
      enteroendocrine hormone glucagon-like peptide-1 (GLP-1) and GLP-1 receptor (GLP
      1R), respectively. Following 3h MSG exposure of the enteroendocrine pGIP/neo: STC
      1 cell line model (500MUg/ml) significantly increased GLP-1 secretion (1.8 fold;
      P<=0.001), however, 72h exposure (500MUg/ml) caused a 1.8 fold decline (P<=0.05).
      Also, 3h MSG exposure (0.5-500MUg/ml) did not induce any cytotoxicity (including
      multiple pre-lethal markers) but 72h exposure at 250-500MUg/ml, decreased cell
      number (11.8-26.7%; P<=0.05), increased nuclear area (23.9-29.8%; P<=0.001) and
      decreased mitochondrial membrane potential (13-21.6%; P<=0.05). At 500MUg/ml, MSG
      increased mitochondrial mass by 16.3% (P<=0.01). MSG did not agonise or
      antagonise internalisation of the GLP-1R expressed recombinantly in U2OS cells,
      following GLP-1 stimulation. In conclusion, 72h exposure of an enteroendocrine
      cell line at dietary levels of MSG, results in pre-lethal cytotoxicity and
      decline in GLP-1 secretion. These adverse events may play a role in the
      pathogenesis of obesity as outlined in the obesogen hypothesis by impairing GLP-1
      secretion, related satiety responses and glucose-stimulated insulin release.

PMID- 27890807
TI  - Diosmin-induced senescence, apoptosis and autophagy in breast cancer cells of
      different p53 status and ERK activity.
AB  - Relatively low bioavailability of plant-derived nutraceuticals with anticancer
      properties may limit their usefulness for prevention and therapy of cancer. In
      the present study, we have screened for nutraceuticals (n=30) that would act at
      low micromolar range against phenotypically distinct breast cancer cell lines,
      namely MCF-7 (ER+, PR+/-, HER2-), MDA-MB-231 (ER-, PR-, HER2-) and SK-BR-3 (ER-,
      PR-, HER2+), and diosmin, a citrus fruit flavonoid belonging to a flavone
      subclass, was selected. MCF-7 cell line was found to be the most sensitive to
      diosmin treatment. Diosmin caused G2/M cell cycle arrest, elevation in p53, p21
      and p27 levels and stress-induced premature senescence when used at lower
      concentrations (5 and 10MUM). Diosmin (20MUM) also promoted apoptosis that was
      not observed in normal human mammary epithelial cells (HMEC). Diosmin stimulated
      oxidative and nitrosative stress, DNA damage and changes in global DNA
      methylation patterns. The status of p53 (wild type versus mutant) and the levels
      of phosphorylated ERK1/2 in a steady state, and diosmin-induced autophagy may
      reflect diverse response to diosmin treatment in MCF-7, MDA-MB-231 and SK-BR-3
      cells, which in turn results in different cell fates. Taken together, diosmin
      that acts at low micromolar range against breast cancer cells may be considered
      as a promising candidate for anticancer therapy.

PMID- 27890808
TI  - Use of physiologically based kinetic modeling-facilitated reverse dosimetry of in
      vitro toxicity data for prediction of in vivo developmental toxicity of
      tebuconazole in rats.
AB  - Toxicological hazard and risk assessment largely rely on animal testing. For
      economic and ethical reasons, the development and validation of reliable
      alternative methods for these animal studies, such as in vitro assays, are
      urgently needed. In vitro concentration-response curves, however, need to be
      translated into in vivo dose-response curves for risk assessment purposes. In the
      present study, we translated in vitro concentration-response data of the
      antifungal compound tebuconazole, obtained in the ES-D3 cell differentiation
      assay, into predicted in vivo dose-response data for developmental toxicity using
      physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry. Using
      the predicted in vivo dose-response data BMD(L)10 values for developmental
      toxicity in rat were calculated and compared with NOAEL values for developmental
      toxicity data in rats as reported in the literature. The results show that the
      BMDL10 value from predicted dose-response data are a reasonable approximation of
      the NOAEL values (ca. 3-fold difference). It is concluded that PBK modeling
      facilitated reverse dosimetry of in vitro toxicity data is a promising tool to
      predict in vivo dose-response curves and may have the potential to define a point
      of departure for deriving safe exposure limits in risk assessment.

PMID- 27890804
TI  - Quantitative sodium MR imaging: A review of its evolving role in medicine.
AB  - Sodium magnetic resonance (MR) imaging in humans has promised metabolic
      information that can improve medical management in important diseases. This
      technology has yet to find a role in clinical practice, lagging proton MR imaging
      by decades. This review covers the literature that demonstrates that this delay
      is explained by initial challenges of low sensitivity at low magnetic fields and
      the limited performance of gradients and electronics available in the 1980s.
      These constraints were removed by the introduction of 3T and now ultrahigh (>=7T)
      magnetic field scanners with superior gradients and electronics for proton MR
      imaging. New projection pulse sequence designs have greatly improved sodium
      acquisition efficiency. The increased field strength has provided the expected
      increased sensitivity to achieve resolutions acceptable for metabolic
      interpretation even in small target tissues. Consistency of quantification of the
      sodium MR image to provide metabolic parametric maps has been demonstrated by
      several different pulse sequences and calibration procedures. The vital roles of
      sodium ion in membrane transport and the extracellular matrix will be reviewed to
      indicate the broad opportunities that now exist for clinical sodium MR imaging.
      The final challenge is for the technology to be supplied on clinical >=3T
      scanners.

PMID- 27890809
TI  - Germ cell responses to doxorubicin exposure in vitro.
AB  - Anthracyclines such as doxorubicin (Dox), widely used to treat various types of
      tumours, may result in induced testicular toxicity and oxidative stress. The
      present investigation was designed to determine whether exposure of isolated and
      purified mouse germ cells to Dox induces DNA damage in the form of strand breaks
      (presumably) resulting in apoptosis and to investigate the relative sensitivity
      of specific cell types. DNA damage was assessed using the Comet assay and the
      presence of apoptosis was determined by TUNEL assay. Isolated mouse germ cells
      were treated with different concentrations (0.05, 0.5 and 1mM, respectively) of
      Dox, and fixed 1h after treatment. The incidences of both DNA damage shown by
      single cell gel-electrophoresis and of apoptosis increased significantly in each
      specific cell type in a concentration-dependent manner. The DNA damage and
      apoptosis incidences gradually increased with concentration from 0.05 to 1mM with
      Dox. Our results indicate that apoptosis plays a vital role in the induction of
      germ cell phase-specific toxicity caused by Dox with pre-meiotically and
      meiotically dividing spermatogonia and spermatocytes respectively as highly
      susceptible target cells.

PMID- 27890811
TI  - Enteric fever in Barcelona: Changing patterns of importation and antibiotic
      resistance.
AB  - BACKGROUND: Enteric fever's incidence is decreasing among residents of high
      income countries, although it's rising in travelers coming from low-resource
      endemic settings. The study's aim is to describe epidemiological, clinical and
      laboratory features of patients with enteric fever. METHODS: Retrospective
      descriptive study of enteric fever cases diagnosed at a Tropical Medicine Unit in
      Barcelona, 1993-2012. RESULTS: Out of 40 patients, 31(77,5%) were returning
      travelers, and 70% of them had been in Southern Asia. In the rest of patients
      without an antecedent of a recent travel, the infection occurred mainly before
      year 2000. The more frequently reported symptoms were fever and diarrhea, lacking
      significant differences between S. typhi and S. paratyphi infections. Quinolones
      were used as empiric treatment in 47.2% of patients, 36.1% received 3rd
      generation cephalosporins, 2.78% azithromycin and 13.89% other combinations.
      Resistance to quinolones in the S. paratyphi group (66.7%) was significantly
      higher compared with the S. typhi group (20%) (p:0.02). 22.5% of patients had
      treatment failure and 23.6% patients presented complications, none of them had
      been previously vaccinated. CONCLUSIONS: The diagnosis of enteric fever was more
      frequent among travelers coming from Southern-East Asia. Quinolone resistance is
      widely spread, particularly in S. paratyphi serotypes and should not be
      considered as first choice treatment anymore.

PMID- 27890812
TI  - Burden of tuberculosis in migrants in Honduras: Potential implications for spread
      of resistant mycobacteria.

PMID- 27890813
TI  - International travel is a risk factor for extended-spectrum beta-lactamase
      producing Enterobacteriaceae acquisition in children: A case-case-control study
      in an urban U.S. hospital.
AB  - BACKGROUND: Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL)
      infections are increasing in both adults and children. The aim of this study was
      to describe the epidemiology of children with ESBL in an ethnically-diverse
      population, to determine what proportion of these infections were community
      onset, and to identify risk factors predisposing children to ESBL acquisition.
      METHODS: A case-case-control study of children aged 0-18 years was conducted from
      2012 to 2014. Patients with ESBL (detected via VITEK2) were matched 1:1:5 (based
      on age, sex, specimen source, and healthcare setting) with non-ESBL and
      uninfected controls. Data on prior antibiotic and healthcare exposure,
      international travel, prior urinary tract infection (UTI), comorbid
      gastrointestinal (GI), genitourinary (GU), neurologic, and immunocompromising
      conditions were collected and compared. RESULTS: Seventy-six patients were
      identified with 85 ESBL infections, of which 77 (91%) were E. coli. ESBL was
      isolated most frequently from urine (n = 72, 85%). Most infections were community
      onset (n = 76, 89%) and were managed in the ambulatory setting (n = 47, 62%). On
      multivariate analysis, international travel (p < 0.001, OR 8.93; CI 2.92-27.78),
      comorbid GI condition (p = 0.002, OR 2.65, CI 1.36-5.15), Asian race (p = 0.005,
      OR 2.56, CI 1.34-4.89) and prior UTI (p < 0.001, OR 8.06, CI 3.47-18.87) were
      significant risk factors for ESBL. CONCLUSION: Most ESBL infections in this study
      were community-onset. To our knowledge, this is the first description of
      international travel as a risk factor for ESBL acquisition in children in the
      United States.

PMID- 27890814
TI  - Response to comment by Juan Segura-Aguilar: New preclinical model are required to
      discover neuroprotective compound in Parkinson's disease.

PMID- 27890810
TI  - Interaction of language, auditory and memory brain networks in auditory verbal
      hallucinations.
AB  - Auditory verbal hallucinations (AVH) occur in psychotic disorders, but also as a
      symptom of other conditions and even in healthy people. Several current theories
      on the origin of AVH converge, with neuroimaging studies suggesting that the
      language, auditory and memory/limbic networks are of particular relevance.
      However, reconciliation of these theories with experimental evidence is missing.
      We review 50 studies investigating functional (EEG and fMRI) and anatomic
      (diffusion tensor imaging) connectivity in these networks, and explore the
      evidence supporting abnormal connectivity in these networks associated with AVH.
      We distinguish between functional connectivity during an actual hallucination
      experience (symptom capture) and functional connectivity during either the
      resting state or a task comparing individuals who hallucinate with those who do
      not (symptom association studies). Symptom capture studies clearly reveal a
      pattern of increased coupling among the auditory, language and striatal regions.
      Anatomical and symptom association functional studies suggest that the
      interhemispheric connectivity between posterior auditory regions may depend on
      the phase of illness, with increases in non-psychotic individuals and first
      episode patients and decreases in chronic patients. Leading hypotheses involving
      concepts as unstable memories, source monitoring, top-down attention, and hybrid
      models of hallucinations are supported in part by the published connectivity
      data, although several caveats and inconsistencies remain. Specifically, possible
      changes in fronto-temporal connectivity are still under debate. Precise
      hypotheses concerning the directionality of connections deduced from current
      theoretical approaches should be tested using experimental approaches that allow
      for discrimination of competing hypotheses.

PMID- 27890815
TI  - Passive drug permeation through membranes and cellular distribution.
AB  - Although often overlooked, passive mechanisms can lead to significant
      accumulation or restriction of drugs to intracellular sites of drug action. These
      mechanisms include lipoidal diffusion of ionized species and pH partitioning
      according to the electrochemical potential and to pH gradients that exist across
      subcellular compartments, respectively. These mechanisms are increasingly being
      exploited in the design of safe and effective drugs for the treatment of a wide
      variety of diseases. In this work, the authors review these efforts and the
      associated passive mechanisms of cellular drug permeation. A generic mathematical
      model of the cell is provided and used to illustrate concepts relevant to steady
      state intracellular distribution. Finally, the authors review methods for
      estimating determinant parameters and measuring the net effect at the level of
      unbound intracellular drug concentrations.

PMID- 27890816
TI  - Pathophysiology of hemophilic arthropathy and potential targets for therapy.
AB  - Hemophilia is a congenital clotting factor deficiency characterized by
      spontaneous and trauma-related bleeding. Spontaneous bleeding shows a
      predilection for joints, and repeated hemarthroses lead to a disabling condition
      called hemophilic arthropathy. Treatment of this condition consists of preventing
      joint bleeding on the one hand and orthopedic surgery as a last resort on the
      other. Up till now, there is no disease modifying therapy available to fill the
      gap between these extremes. This review provides an overview of the pathogenesis
      of hemophilic arthropathy in order to identify potential targets for therapy.
      Joint bleeding induces synovial inflammation, cartilage degeneration and bone
      damage. These processes interact with each other and result in a vicious circle.
      Hemarthrosis promotes synovial hypertrophy and neoangiogenesis, increasing the
      susceptibility to mechanical damage and subsequent bleeding. The inflamed
      synovium affects the cartilage, while cartilage is also directly affected by
      blood via the release of cytokines and metalloproteinases, and via hydroxyl
      radical formation inducing chondrocyte apoptosis. Apart from the inflammatory
      pathways, iron plays a pivotal role in this process, as does the fibrinolytic
      system. Considering its pathogenesis, potential targets for disease modifying
      therapy in hemophilic arthropathy are iron, inflammation, vascular remodeling,
      hyperfibrinolysis, bone remodeling and cartilage regeneration. So far, iron
      chelators, anti-inflammatory therapy, anti-fibrinolytics and bone remodeling
      agents have demonstrated beneficial effects, predominantly in a preclinical
      setting. There is still a long way to go before these interventions will
      translate into clinical practice. The most important challenges are: establishing
      a universal outcome measure to predict efficacy in humans, and determination of
      the optimal route and timing to administer disease modifying therapy.

PMID- 27890818
TI  - The anabolic steroid nandrolone alters cannabinoid self-administration and brain
      CB1 receptor density and function.
AB  - Clinical and pre-clinical observations indicate that anabolic-androgenic steroids
      can induce neurobiological changes that alter the rewarding effects of drugs of
      abuse. In this study, we investigated the effect of the anabolic steroid
      nandrolone on the rewarding properties of the cannabinoid CB1 receptor agonist
      WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly
      with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to
      self-administer WIN (12.5MUg/kg/infusion) intravenously. After reaching stable
      drug intake, self-administration behavior was extinguished to examine drug- and
      cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral
      parameters presumed to influence drug-taking and drug-seeking behaviors were
      examined to gain more insight into the behavioral specificity of nandrolone
      treatment. Finally, animals were sacrificed for analysis of CB1 receptor density
      and function in selected brain areas. We found that nandrolone-treated rats self
      administered up to 2 times more cannabinoid than vehicle-treated rats, but
      behaved similarly to control rats when tested for drug- and cue-induced
      reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by
      nandrolone-treated rats was not accompanied by changes in locomotor activity,
      sensorimotor gating, or memory function. However, our molecular data show that
      after chronic WIN self-administration nandrolone-treated rats display altered CB1
      receptor density and function in selected brain areas. We hypothesize that
      increased cannabinoid self-administration in nandrolone-treated rats results from
      a nandrolone-induced decrease in reward function, which rats seem to compensate
      by voluntarily increasing their cannabinoid intake. Altogether, our findings
      corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids
      induces dysfunction of the reward pathway in rats and might represent a potential
      risk factor for abuse of cannabis and other drugs in humans.

PMID- 27890819
TI  - Reply to the letter addressed by Amr A. EL-Arabey "Dual function of OCT-2 and
      MATE1 in Cisplatin induced nephrotoxicity".

PMID- 27890817
TI  - sec-Butylpropylacetamide (SPD), a new amide derivative of valproic acid for the
      treatment of neuropathic and inflammatory pain.
AB  - Chronic pain is a multifactorial disease comprised of both inflammatory and
      neuropathic components that affect ~20% of the world's population. sec
      Butylpropylacetamide (SPD) is a novel amide analogue of valproic acid (VPA)
      previously shown to possess a broad spectrum of anticonvulsant activity. In this
      study, we defined the pharmacokinetic parameters of SPD in rat and mouse, and
      then evaluated its antinociceptive potential in neuropathic and acute
      inflammatory pain models. In the sciatic nerve ligation (SNL) model of
      neuropathic pain, SPD was equipotent to gabapentin and more potent than its
      parent compound VPA. SPD also showed either higher or equal potency to VPA in the
      formalin, carrageenan, and writhing tests of inflammatory pain. SPD showed no
      effects on compound action potential properties in a sciatic nerve preparation,
      suggesting that its mechanism of action is distinct from local anesthetics and
      membrane stabilizing drugs. SPD's activity in both neuropathic and inflammatory
      pain warrants its development as a potential broad-spectrum anti-nociceptive
      drug.

PMID- 27890820
TI  - Recent developments in natural product-based drug discovery for tuberculosis.
AB  - Natural products (NPs) have been at the origin of several established drugs
      against tuberculosis (TB). Although the current clinical TB pipeline does not
      feature any candidates derived from new NP scaffolds, numerous novel NPs or NP
      analogs have been discovered in the recent past with promising activity against
      Mycobacterium tuberculosis (Mtb). This includes newly discovered structures as
      well as known NP classes that had not been previously recognized to be active
      against Mtb. These compounds could help to replenish the dry clinical TB pipeline
      and, thus, contribute to improvements in the treatment of a devastating disease.

PMID- 27890821
TI  - Molecular dynamics-driven drug discovery: leaping forward with confidence.
AB  - Given the significant time and financial costs of developing a commercial drug,
      it remains important to constantly reform the drug discovery pipeline with novel
      technologies that can narrow the candidates down to the most promising lead
      compounds for clinical testing. The past decade has witnessed tremendous growth
      in computational capabilities that enable in silico approaches to expedite drug
      discovery processes. Molecular dynamics (MD) has become a particularly important
      tool in drug design and discovery. From classical MD methods to more
      sophisticated hybrid classical/quantum mechanical (QM) approaches, MD simulations
      are now able to offer extraordinary insights into ligand-receptor interactions.
      In this review, we discuss how the applications of MD approaches are
      significantly transforming current drug discovery and development efforts.

PMID- 27890822
TI  - Visual light effects on mitochondria: The potential implications in relation to
      glaucoma.
AB  - Light of different wave-lengths have the potential to interact with four major
      mitochondrial protein complexes that are involved in the generation of ATP.
      Neurones of the central nervous system have an absolute dependence on
      mitochondrial generated ATP. Laboratory studies show that short-wave or blue
      light (400-480nm) that impinges on the retina affect flavin and cytochrome
      constituents associated with mitochondria to decrease the rate of ATP formation,
      stimulate ROS and results in cell death. This suggests that blue light could
      potentially have a negative influence on retinal ganglion cell (RGC) mitochondria
      that are abundant and not shielded by macular pigments as occurs for
      photoreceptor mitochondria. This might be of significance in glaucoma where it is
      likely that RGC mitochondria are already affected and therefore be more
      susceptible to blue light. Thus simply filtering out some natural blue light from
      entering the eye might be beneficial for the treatment of glaucoma. Long-wave or
      red light (650-800nm) affects mitochondrial complex IV or cytochrome oxidase to
      increase the rate of formation of ATP and ROS causing the generation of a number
      of beneficial factors. Significantly, laboratory studies show that increasing the
      normal amount of natural red light reaching rat RGC mitochondria in situ,
      subjected to ischemia, proved to be beneficial. A challenge now is to test
      whether extra red light delivered to the human retina can slow-down RGC loss in
      glaucoma. Such a methodology has also the advantage of being non-invasive. One
      very exciting possibility might be in the production of a lens where solar UV
      light is convertes to add to the amount of natural red light entering the eye.

PMID- 27890823
TI  - Assessment of thyroid function in intensive care unit patients by liquid
      chromatography tandem mass spectrometry methods.
AB  - OBJECTIVES: Patients with non-thyroidal illness syndrome have many abnormalities
      in thyroid hormone tests. Such patients have medical comorbidities associated
      with low serum proteins and are on multiple medications that interfere with
      thyroid hormone measurement by immunoassay platforms. It is unknown if these
      thyroid hormone measurements reflect physiologic conditions or if they are
      artifacts of testing methodology. METHODS: Fifty patients were selected from the
      intensive care unit (ICU) from our institution. Total and free thyroid hormones
      in plasma were measured by gold standard liquid chromatography-tandem mass
      spectrometry (LC-MSMS). The results were compared to the Roche Cobas 6000.
      Patient medical comorbidities and binding protein levels were assessed. RESULTS:
      Concentrations of total 3,5,5'-triidothyronine (TT3) and total thyroxine (TT4)
      were significantly more likely to be low by LC-MSMS compared to immunoassay. Free
      3,5,5'-triidothyronine (FT3) levels were similar by immunoassay and LC-MSMS.
      However, FT4 concentrations were mildly elevated for many patients when measured
      by ultrafiltration LC-MSMS (19/50, 38%) compared to 1/50 (2%) when measured by
      immunoassay (p=0.0001). Decreased albumin and thyroxine binding globulin were
      common and patients were on an average of 11.7+/-5.0 medications, all factors
      known to interfere with results found on immunoassays. CONCLUSIONS: Marked
      discrepancies in thyroid hormone measurement were noted between reference LC-MSMS
      and a common immunoassay platform. It is hypothesized that T4 binding to low
      affinity albumin is displaced by several drugs, raising concentrations of FT4 by
      LC-MSMS compared to immunoassay, and that the immunoassay values are falsely
      decreased due to low binding proteins in our patient population.

PMID- 27890824
TI  - Evaluating a switch from meconium to umbilical cord tissue for newborn drug
      testing: A retrospective study at an academic medical center.
AB  - BACKGROUND: The objective of this study was to compare detection rates of newborn
      drug exposure at an academic medical center transitioning from meconium to
      umbilical cord tissue toxicology testing. METHODS: We performed an Institutional
      Review Board-approved retrospective chart review on all newborns (n=2072) for
      whom newborn drug testing was ordered at our academic medical center between June
      2012 and August 2015 (in August 2013, umbilical cord tissue became the preferred
      specimen). RESULTS: Meconium toxicology testing was positive for at least one
      compound in 221 cases (21.3% of 1037 total specimens), with non-medical drug use
      identified in 85 cases (8.2%). Umbilical cord tissue toxicology testing was
      positive for at least one compound in 302 cases (29.2%), with non-medical drug
      use identified in 107 cases (10.3%). Of the cases involving non-medical drug use,
      the most common compounds detected were tetrahydrocannabinol and amphetamines.
      Non-medical drug use did not differ significantly between meconium and umbilical
      cord tissue, either as a total or for classes of drugs such as amphetamines,
      cannabinoids, and opiates. Maternal non-medical use of tramadol (not tested for
      in meconium) was identified in 5 cases (0.4%). There were significant differences
      in rate of detection of iatrogenic medications. Specifically, morphine,
      lorazepam, phenobarbital, and codeine were more commonly detected in meconium,
      while oxycodone was more commonly detected in umbilical cord tissue. CONCLUSIONS:
      Umbilical cord tissue toxicology testing yielded a similar detection rate
      compared to meconium testing. The use of umbilical cord tissue avoids detection
      of medications given to the neonate prior to meconium collection.

PMID- 27890825
TI  - The expression of chemorepulsive guidance receptors and the regenerative
      abilities of spinal-projecting neurons after spinal cord injury.
AB  - Spinal cord injury (SCI) in mammals leads to permanent loss of function because
      axons do not regenerate in the central nervous system (CNS). To date, treatments
      based on neutralizing inhibitory environmental cues, such as the myelin
      associated growth inhibitors and chondroitin sulfate proteoglycans, or on adding
      neurotrophic factors, have had limited success in enhancing regeneration.
      Published studies suggested that multiple axon guidance cues (repulsive guidance
      molecule (RGM) family, semaphorins, ephrins, and netrins) persist in adult
      animals, and that their expression is upregulated after CNS injury. Moreover,
      many adult CNS neurons continue to express axon guidance receptors. We used the
      advantages of the lamprey CNS to test the hypotheses that the regenerative
      abilities of spinal-projecting neurons depend upon their expression of
      chemorepulsive guidance receptors. After complete spinal transection, lampreys
      recover behaviorally, and injured axons grow selectively in their correct paths.
      However, the large identified reticulospinal (RS) neurons in the lamprey brain
      are heterogeneous in their regenerative abilities - some are high regeneration
      capacity neurons (probability of axon regeneration >50%), others are low
      regeneration capacity neurons (<30%). Here we report that the RGM receptor
      Neogenin is expressed preferentially in the low regeneration capacity RS neurons
      that regenerate poorly, and that downregulation of Neogenin by morpholino
      antisense oligonucleotides enhances regeneration of RS axons after SCI. Moreover,
      lamprey CNS neurons co-express multiple guidance receptors (Neogenin, UNC5 and
      PlexinA), suggesting that the regenerative abilities of spinal-projecting neurons
      might reflect the summed influences of the chemorepulsive guidance receptors that
      they express.

PMID- 27890826
TI  - Relevant variations and neuroprotecive effect of hydrogen sulfide in a rat
      glaucoma model.
AB  - Glaucoma is an irreversible and blinding neurodegenerative disease of the eye,
      and is characterized by progressive loss of retinal ganglion cells (RGCs). Since
      endogenous hydrogen sulfide (H2S) was reported to be involved in
      neurodegeneration in the central nervous system, the authors aimed to develop a
      chronic ocular hypertension (COH) rat model simulating glaucoma and therein test
      the H2S level together with the retinal protein expressions of related synthases,
      and further investigated the effect of exogenous H2S supplement on RGC survival.
      COH rat model was induced by cross-linking hydrogel injection into anterior
      chamber, and the performance of the model was assessed by intraocular pressure
      (IOP) measurement, RGC counting and retinal morphological analysis. Endogenous
      H2S level was detected along with the retinal protein expressions of H2S-related
      synthases cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE) and
      3-mercaptopyruvate sulfurtransferase (3-MST) in the COH rats. Retinal H2S level
      and RGC survival were evaluated again after NaHS (a H2S donor) treatment in the
      COH rats. The results showed that the COH model succeeded in simulating glaucoma
      features, and retinal H2S level decreased significantly when the retinal protein
      expressions of CBS, CSE and 3-MST were downregulated generally in the COH rats.
      Furthermore, the decrease of retinal H2S level and loss of RGCs were both
      improved by NaHS treatment in experimental glaucoma, without obvious variation of
      IOP. Our study revealed that the intracameral injection of cross-linking hydrogel
      worked efficiently in modeling glaucoma, and H2S had protective effect on RGCs
      and might be involved in the pathological mechanism of glaucomatous neuropathy.

PMID- 27890828
TI  - Alterations of motor cortical microcircuit in a depressive-like mouse model
      produced by light deprivation.
AB  - Depression is one of the most prevalent and life-threatening forms of mental
      illness. The heavy social burden imposed by this disorder calls for a better
      understanding of its pathogenesis. Light deficiency is an important factor
      potentially leading to depression. However, how the light deficiency affects
      neural microcircuit underlying depression remains largely unknown. This study
      investigated the properties of morphology, electrophysiology, and synaptology of
      layer V pyramidal cells (L5PCs) in the motor cortex of a mouse model with
      depressive behavioral phenotype that was produced by light deprivation (LD). The
      depressive behavioral phenotype was characterized by increased immobility and
      decreased locomotor activity in behavioral tests. LD decreased burst firing
      neurons and suppressed the intrinsic excitability of L5PCs, and also reduced the
      neuronal morphological complexity as evidenced by simplified basal and apical
      dendrites. Moreover, LD reduced the synaptic connecting probability of L5PCs.
      These alterations of the simplified morphology, the suppressed excitability, and
      the reduced connecting probability of L5PCs together could well explain the
      depression-like behaviors of the mouse model. However, it was surprising to find
      that the excitatory postsynaptic potentials (EPSPs) of single L5PC connections
      were significantly enhanced and the paired pulse ratio (EPSP2/EPSP1) was
      significantly increased. These synaptological results indicate that the absolute
      synaptic strength of single L5PC connections was enhanced and the transmitter
      release probability was increased although the connections between L5PCs became
      sparse. Therefore, a compensation mechanism accompanied the negative changes that
      were consistent with the depressive behavioral phenotype. Our findings from the
      motor cortex of depression-like behavior mice may underlie the neural
      microcircuit mechanism of depression, providing insights into the pathogenesis of
      depression at a level of single neurons and synaptic connections.

PMID- 27890829
TI  - Antenatal exposure to antidepressants is associated with altered brain
      development in very preterm-born neonates.
AB  - BACKGROUND: Antenatal exposure to selective serotonin reuptake inhibitors (SSRIs)
      is associated with an enhanced risk of preterm birth. Very preterm-born neonates
      (<32weeks' gestation) antenatally-exposed to SSRIs may show altered brain
      development. OBJECTIVE: To examine whether antenatal-SSRI exposure was associated
      with adverse neonatal brain microstructural and metabolic development using
      diffusion tensor and magnetic resonance spectroscopic imaging. DESIGN/METHODS: Of
      177 neonates enrolled, 14 (8%) were antenatally exposed to SSRIs. Neonates were
      scanned twice (median week 32; interquartile range [IQR]: 30.4-33.6) and again at
      term-equivalent age (40.1, IQR: 38.6-42.1). Using a region-of-interest approach,
      N-acetylaspartate to choline ratios (NAA/Cho), lactate to choline ratios, white
      and gray matter fractional anisotropy (FA), mean, axial, radial diffusivity (MD,
      AD, RD) values were extracted from white and gray matter subcortical regions.
      Neurodevelopment was assessed at 18 months, corrected age. RESULTS: SSRI-exposed
      neonates exhibited increased FA and decreased MD, AD and RD values in the
      superior white matter (p<0.05). FA values in the basal ganglia and thalamus were
      significantly lower in neonates antenatally exposed to SSRIs, compared to non
      exposed (p=0.004). Lower NAA/Cho values (p=0.04) and higher Lactate/Cho values
      (p=0.004) in posterior gray matter were evident in neonates exposed to SSRIs. No
      association with antenatal-SSRI exposure and neurodevelopment was evident.
      CONCLUSIONS: Given the importance of treating depression in mothers at risk for
      preterm delivery, the impact of antenatal-SSRIs on early brain development
      requires further attention. Future research is directed at determining the
      mechanism of this relationship and the contribution of maternal mood.

PMID- 27890827
TI  - Adolescent GBR12909 exposure induces oxidative stress, disrupts parvalbumin
      positive interneurons, and leads to hyperactivity and impulsivity in adult mice.
AB  - The adolescent period in mammals is a critical period of brain maturation and
      thus represents a time of susceptibility to environmental insult, e.g.
      psychosocial stress and/or drugs of abuse, which may cause lasting impairments in
      brain function and behavior and even precipitate symptoms in at-risk individuals.
      One likely effect of these environmental insults is to increase oxidative stress
      in the developing adolescent brain. Indeed, there is increasing evidence that
      redox dysregulation plays an important role in the development of schizophrenia
      and other neuropsychiatric disorders and that GABA interneurons are particularly
      susceptible to alterations in oxidative stress. The current study sought to model
      this adolescent neurochemical "stress" by exposing mice to the dopamine
      transporter inhibitor GBR12909 (5mg/kg; IP) during adolescence (postnatal day 35
      44) and measuring the resultant effect on locomotor behavior and probabilistic
      reversal learning as well as GABAergic interneurons and oxidative stress in
      adulthood. C57BL6/J mice exposed to GBR12909 showed increased activity in a novel
      environment and increased impulsivity as measured by premature responding in the
      probabilistic reversal learning task. Adolescent GBR12909-exposed mice also
      showed decreased parvalbumin (PV) immunoreactivity in the prefrontal cortex,
      which was accompanied by increased oxidative stress in PV+ neurons. These
      findings indicate that adolescent exposure to a dopamine transporter inhibitor
      results in loss of PV in GABAergic interneurons, elevations in markers of
      oxidative stress, and alterations in behavior in adulthood.

PMID- 27890831
TI  - Neural plasticity during motor learning with motor imagery practice: Review and
      perspectives.
AB  - In the last decade, many studies confirmed the benefits of mental practice with
      motor imagery. In this review we first aimed to compile data issued from
      fundamental and clinical investigations and to provide the key-components for the
      optimization of motor imagery strategy. We focused on transcranial magnetic
      stimulation studies, supported by brain imaging research, that sustain the
      current hypothesis of a functional link between cortical reorganization and
      behavioral improvement. As perspectives, we suggest a model of neural adaptation
      following mental practice, in which synapse conductivity and inhibitory
      mechanisms at the spinal level may also play an important role.

PMID- 27890830
TI  - Time-course of glial changes in the hyperhomocysteinemia model of vascular
      cognitive impairment and dementia (VCID).
AB  - Vascular cognitive impairment and dementia (VCID) is the second leading cause of
      dementia behind Alzheimer's disease (AD) and is a frequent co-morbidity with AD.
      Despite its prevalence, little is known about the molecular mechanisms underlying
      the cognitive dysfunction resulting from cerebrovascular disease. Astrocytic end
      feet almost completely surround intraparenchymal blood vessels in the brain and
      express a variety of channels and markers indicative of their specialized
      functions in the maintenance of ionic and osmotic homeostasis and gliovascular
      signaling. These functions are mediated by end-foot enrichment of the aquaporin 4
      water channel (AQP4), the inward rectifying potassium channel Kir4.1 and the
      calcium-dependent potassium channel MaxiK. Using our hyperhomocysteinemia (HHcy)
      model of VCID we examined the time-course of astrocytic end-foot changes along
      with cognitive and neuroinflammatory outcomes. We found that there were
      significant astrocytic end-foot disruptions in the HHcy model. AQP4 becomes
      dislocalized from the end-feet, there is a loss of Kir4.1 and MaxiK protein
      expression, as well as a loss of the Dp71 protein known to anchor the Kir4.1,
      MaxiK and AQP4 channels to the end-foot membrane. Neuroinflammation occurs prior
      to the astrocytic changes, while cognitive impairment continues to decline with
      the exacerbation of the astrocytic changes. We have previously reported similar
      astrocytic changes in models of cerebral amyloid angiopathy (CAA) and therefore,
      we believe astrocytic end-foot disruption could represent a common cellular
      mechanism of VCID and may be a target for therapeutic development.

PMID- 27890832
TI  - Operative Treatment of Type 2 Endoleaks Involving the Inferior Mesenteric Artery.
AB  - BACKGROUND: We report the results of the operative treatment for type 2 endoleak
      (T2E) involving the inferior mesenteric artery (IMA) using the transarterial
      embolization (TAE) or the video laparoscopic ligation (VLS). METHODS: Between
      January 2005 and December 2015, we retrospectively analyzed 901 patients treated
      with endovascular aortic repair (EVAR): 883 (98%) had 1 valid postoperative
      radiologic evaluation, at least. All patients with operative repair for IMA
      related T2E entered the final analysis. Indication of their operative repair was
      sac enlargement (>5 mm within 6 months or >1 cm from the preoperative diameter,
      irrespectively of the postoperational time) and/or its persistence >12 months.
      RESULTS: We detected 192 (21.7%) T2Es, overall. We identified 37 (4.2%) IMA
      related T2Es, and treated 21 cases (VLS n = 11, TAE n = 10). Aneurysm-related
      mortality and major or minor morbidity was never observed. Time of intervention
      did not differ significantly (minutes, VLS = 97 +/- 46 vs. TAE = 95 +/- 21, P =
      0.901). Hospitalization was significantly lower in the TAE group (days, 4 +/- 2
      vs. 1 +/- 0.4, P < 0.001). No patient was lost at a mean follow-up of 46 +/- 32
      months (range, 1-110; median, 48). At last follow-up, sac diameter was
      significantly more stable in the VLS (mm, 60 +/- 10 vs. 55 +/- 7, P = 0.593) than
      that in the TAE group (mm, 57 +/- 9 vs. 63 +/- 10, P = 0.050). The IMA-related
      T2E reintervention rate was not significantly different between the groups (VLS,
      n = 0 [0%] vs. TAE, n = 2 [20.0%], P = 0.213). Secondary aortic reintervention
      rate was 28.6% (n = 6), and secondary open conversion rate was 9.5% (VLS, n = 1
      [9.1%] vs. TAE, n = 1 [10.0%], P = 1). CONCLUSIONS: In authors' experience,
      operative treatment of IMA-related T2E was safe; VLS proved to be effective and
      durable in sealing this type of T2E. Patients receiving correction of IMA-related
      T2E after EVAR remained at risk for development of any type of endoleaks, as well
      as at risk of reintervention.

PMID- 27890833
TI  - Pulse Wave Analysis after Treatment of Abdominal Aortic Aneurysms with the
      Ovation Device.
AB  - BACKGROUND: Ovation aortic stent-graft system is a new device for the
      endovascular treatment of Abdominal Aortic Aneurysms achieving fixation via a 35
      mm long, rigid anchored suprarenal stent and sealing stent at the infrarenal
      level by a means of a polymer-filling pair of inflatable O-rings, which cause
      narrowing of flow lumen and regional stenosis. Thus, concerns have been raised
      regarding hemodynamic consequences associated with this new design. Our
      preliminary report showed no significant increase of aortic pulse wave velocity
      (aPWV) immediately after implantation of the ovation in 3 patients. We studied
      further the hemodynamic implications of the Ovation implantation in 6 patients
      for a follow-up of 6 months. METHODS: A brachial cuff-based automatic
      oscillometric device (Mobil-O-Graph; IEM, Stolberg, Germany) was used to perform
      noninvasively pulse wave analysis and stiffness estimation. Measurements were
      held preoperatively in 6 patients treated for abdominal aortic aneurysm, at the
      end of the first postoperative week, first and sixth postoperative month. Changes
      in systolic and diastolic blood pressure (cSyst, cDiast), heart rate, aPWV,
      augmentation index (AI@75), augmentation pressure (AP), and in the amplitude
      ratio of the reflected-to-forward pressure waves (reflection magnitude, RM) were
      recorded and compared. Significant change in any parameter was examined via
      analysis of variance repeated measures. RESULTS: The cSyst was 132 +/- 19.6, 127
      +/- 17.63, 131.3 +/- 19.96, and 129.83 +/- 31.72 mm Hg (P = 0.81) and cDiast was
      88 +/- 10.58, 86.83 +/- 11.72, 89.83 +/- 16.01, and 98.5 +/- 24.56 mm Hg (P =
      0.40). The heart rate showed an increasing yet nonsignificant tendency (67 +/-
      10.60, 75.1 +/- 8.63, 74.33 +/- 8.89, and 70.66 +/- 6.65 beats/min, 0.27). The
      aPWV remained constant (11.61 +/- 1.88, 11.6 +/- 1.74, 11.8 +/- 2.08, and 11.85
      +/- 2.30 m/sec, P = 0.79). Similarly, RM (71.16 +/- 9.94, 60.66 +/- 11.79, 61.5
      +/- 14.47, and 64.5 +/- 3.78), AI@75 (33.83 +/- 12.25, 22.16 +/- 7.93, 27.83 +/-
      11.23, and 19.5 +/- 14.72), and AP (18.33 +/- 10.36, 9.83 +/- 4.91, 11.5 +/-
      9.22, and 12 +/- 15.08 mm Hg) remained practically unaltered during the follow-up
      period (P value: 0.79, 0.25, 0.10, and 0.27), respectively. CONCLUSIONS: The
      implantation of the Ovation stent graft does not cause increase in aortic
      stiffness or in pulse wave reflection in the mid-period. The rationale of
      investigating noninvasively the impact of aortic stent grafts on the mechanical
      properties and the hemodynamic parameters should be encouraged because such
      findings may contribute to further development of newer endograft designs.

PMID- 27890834
TI  - Eagle Syndrome Presenting after Blunt Trauma.
AB  - As classically described, Eagle syndrome is an entity where patients develop pain
      or neurologic manifestations arising from an elongated styloid process and/or an
      ossified stylohyoid ligament irritating or compressing adjacent cranial nerves or
      the carotid arteries. Over the past few years, there have been reports of actual
      injury to the internal carotid artery with dissection, occlusion, and strokes. We
      present 3 cases identified after blunt trauma: 1 due to carotid compression and 2
      due to actual injury to the internal carotid artery. Eagle syndrome should be a
      consideration in any patient with a carotid injury due to blunt trauma or
      suffering a syncopal episode which led to blunt trauma. Carotid stenting is an
      effective treatment modality for injury to the carotid artery when
      anticoagulation is contraindicated. Styloidectomy is performed for symptoms due
      to carotid artery compression or if there is concern for future carotid injury
      from the styloid process.

PMID- 27890835
TI  - Acute Kidney Injury after Open Repair of Intact Abdominal Aortic Aneurysms.
AB  - BACKGROUND: These last years, considerable attention has been given to renal
      issues following endovascular aortic repair but acute kidney injury (AKI) also
      remains one of the most frequent complications following open repair (OR). Since
      AKI definition has evolved, our aim was to review the etiology, incidence,
      classifications, and consequences of AKI after OR for intact abdominal aortic
      aneurysm (AAA). METHODS: A review of the English language literature published
      between 2004 and 2016 was conducted according to the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Studies regarding
      ruptured AAA, combination of emergency and elective repairs without results
      stratification, and thoracoabdominal aneurysms were excluded, as well as studies
      not using recent consensual AKI classifications. RESULTS: In total, 6 studies
      including 658 patients (394 from prospective studies and 264 from retrospective
      studies) used recent consensual classifications (risk injury failure loss end
      stage renal disease [RIFLE], Acute Kidney Injury Network classification [AKIN],
      kidney disease-improving global outcomes [KDIGO], and Aneurysm Renal Injury Score
      [ARISe]) and were considered for analysis. After infrarenal clamping, AKI rates
      were quite similar between studies, observed in 24% cases when using the RIFLE
      classification, 20% cases with the AKIN criteria, and 26.3% cases when using the
      ARISe classification. Pooled rates of renal replacement therapy (RRT) and 30-day
      mortality were 0.3% and 1.4%, respectively. In the long term, no patient mandated
      chronic RRT. After suprarenal clamping, 2 retrospective studies used the RIFLE
      criteria to define the incidence of AKI, and the pooled AKI rate was 36.8%. The
      AKI rate was 26.5% in smaller retrospective study using the KDIGO criteria. Rates
      of RRT and 30-day mortality were 3.8% and 2.9%, respectively. In the long term,
      1.2-3% of patients mandated chronic RRT. CONCLUSIONS: AKI is a common but
      generally transient complication after OR for AAA. Its incidence depends on
      definitions used, and few studies were found to use recent consensual AKI
      criteria. In the future, large prospective studies using consensual AKI
      definitions will facilitate comparison between repair strategies.

PMID- 27890836
TI  - Microcirculation Evaluated by Intraoperative Fluorescence Angiography after
      Tibial Bypass Surgery.
AB  - BACKGROUND: Intact microperfusion of the foot in the critical ischemic limb
      remains a crucial condition for ulcer healing. Aim of this clinical study was to
      evaluate the immediate effect of tibial bypass surgery on the microcirculation by
      usage of fluorescence angiography. METHODS: Prospective analysis of 33 patients
      presenting with critical limb ischemia (Rutherford IV-VI) undergoing tibial
      bypass surgery was performed. Macroperfusion was investigated by measurement of
      ankle-brachial index. For assessment of microperfusion, intraoperative
      fluorescence angiography (SPY Elite, NOVADAQ) was undertaken during general
      anesthesia immediately before and after operation. For each investigation, a
      fluorescence dye (Indocyanine green) with an amount of 0.1 mg/kg was administered
      intravenously. Follow-up investigations were performed to assess the clinical
      outcome. RESULTS: The mean follow-up time was 8.28 (+/-4.46) months. The
      parameters Ingress (IN) and Ingress rate (InR) of the fluorescence dye
      representing the microcirculation showed a significant improvement to
      preoperative values and correlated with the ankle-brachial index significantly.
      Furthermore, a significant difference between the individual improvement of the
      microcirculation parameters (preoperative-postoperative) between patients with
      postoperative clinical improvement (wound healing, absence of rest pain) and
      those without could be demonstrated (InR: P = 0.039, IN: P = 0.036). CONCLUSIONS:
      The parameters IN and InR significantly reproduced the postoperative improvement
      of the microcirculation. An increased ankle-brachial index significantly
      correlated with increased microcirculation parameters. A better clinical outcome
      was found in those patients who had a higher relative improvement of
      microcirculation postoperatively.

PMID- 27890837
TI  - Association between Prehospital Time and Mortality following Blunt Thoracic
      Aortic Injuries.
AB  - BACKGROUND: Blunt thoracic aortic injuries (BTAIs) can be lethal, but advances in
      trauma systems and surgical care have helped reduce mortality. The purpose of
      this study is to investigate whether time from injury to presentation is
      associated with mortality following BTAI. METHODS: Using the Ontario Trauma
      Registry, all patients were identified who were hospitalized with BTAI between
      1999 and 2009. Variables including age, sex, Injury Severity Score, Charlson
      comorbidity index, systolic blood pressure on admission, operative intervention,
      and time from injury to presentation were analyzed using multivariate logistic
      regression to determine independent predictors of mortality. RESULTS: We
      identified 264 cases of BTAI that survived until hospital admission. Of these,
      220 patients had documented time from injury to presentation to hospital. Most,
      68.2% (n = 150), presented within 60 min of injury. On adjusted multivariate
      analysis, a prehospital time of <=60 min independently predicted higher mortality
      (odds ratio 0.27, 95% confidence interval 0.08-0.89, P = 0.03). Tight clustering
      was seen with prehospital time and mortality. CONCLUSIONS: Rather than reducing
      mortality as hypothesized, a shorter time between BTAI and hospital presentation
      (<60 min) is associated with increased mortality. This may be the result of
      selection bias with the quicker transport of more severely injured patients.

PMID- 27890839
TI  - Rupture of a True Profunda Femoris Artery Aneurysm: Two Case Reports and Review
      of the English Language Literature.
AB  - Profunda femoris artery aneurysms (PFAAs) are very rare and easily overlooked
      because they are located deeply within thigh muscle. PFAAs have a high rate of
      rupture in comparison with other peripheral arterial aneurysms, resulting in
      emergency surgical procedures with significant morbidity. PFAA is diagnosed with
      color arterial Doppler ultrasound, although computed tomography angiography
      remains the best imaging method to precisely define the exact site and length of
      arterial involvement. PFAAs should be treated surgically once diagnosed, even if
      they are asymptomatic due to the high incidence of complications. Currently,
      around 28 patients with PFAA rupture, including the 2 cases from this report,
      have been described in the English language literature. In this report, we
      describe the diagnosis and treatment of 2 true ruptured aneurysms of the profunda
      femoris artery with 2 different approaches, and will review the relevant
      literature.

PMID- 27890838
TI  - Preoperative Evaluation of the Renal Function before the Treatment of Abdominal
      Aortic Aneurysms.
AB  - BACKGROUND: Chronic impaired renal function constitutes a major risk factor of
      morbi-mortality during the treatment of an abdominal aortic aneurism (AAA). The
      inflammatory state due to the AAA could result in a reduction in the muscular
      mass and an overestimation of the glomerular filtration rate (GFR) with the usual
      formulas. The objective of this study was to determine if the formulas used to
      evaluate the estimated GFR were adapted in patients with AAA. MATERIALS AND
      METHODS: Between August 2013 and November 2014, we conducted an exploratory study
      to evaluate the renal function before surgery for AAA in 28 patients. The renal
      function was evaluated by (1) the dosage of plasmatic creatinine, (2) the GFR
      estimated with the Cockroft-Gault, Modification of Diet in Renal Disease (MDRD),
      and chronic kidney disease epidemiology collaboration (CKD-EPI) formulas, (3) the
      creatinine clearance (CC), and (4) the direct measurement of the GFR with a
      reference method (iohexol clearance). Statistical analysis was carried out to
      compare and correlate the GFR estimated by the various formulas with the GFR
      measured by the reference technique. RESULTS: The study included 21 men (75%) and
      7 women (25%), with a median age of 76 years (58-89). The measured GFR was
      correlated with the GFR estimated from the CKD-EPI (rho = 0.78, P < 0.0001), the
      MDRD (rho = 0.78, P < 0.0001), the Cockroft-Gault (rho = 0.65, P = 0.0002), and
      CC (rho = 0.86, P < 0.0001). However, there were important individual variations
      between estimated and measured GFR. As regards the detection of the patients
      presenting a GFR <60 mL/min/1.73 m2, the sensitivities of the CKD-EPI, MDRD,
      Cockroft-Gault formulas and CC were 64%, 64%, 71%, and 70%, respectively.
      Specificities were 71%, 79%, 57%, and 100%, respectively. The estimation of the
      GFR by the CKD-EPI formula had the lowest bias (-3.0). Bland-Altman plots
      indicated that the estimation of the GFR by the CKD-EPI formula had the best
      performance in comparison with the other methods. CONCLUSIONS: This study found a
      statistical correlation between the measurement of the GFR and the various
      formulas available to estimation the GFR among AAA patients. The CKD-EPI formula
      is most appropriate. However, there were important individual variations between
      the measurement and the estimations of the GFR. A larger scale study is necessary
      to determine the profile of the patients with a risk of error in the estimation
      of the GFR. The French recommendations on the evaluation of the renal function
      before AAA treatment remain based on serum creatinine and should be revalued.

PMID- 27890840
TI  - Infected Iliac Pseudoaneurysm after Cardiac Catheterization Complicated by
      Girdlestone Pseudoarthroplasty for Recurrent Infection of Hip Prosthesis.
AB  - We report a massive infected pseudoaneurysm of the right external iliac artery in
      the setting of Girdlestone pseudoarthroplasty (GSA) for chronic infection. Around
      the time of her GSA, the patient underwent cardiac catheterization with resultant
      pseudoaneurysm formation. Infection was likely due to spread from her previous
      chronic infection. Delay in presentation occurred due to attribution of her
      symptoms to her GSA. The patient underwent ligation of the right external iliac
      artery and hip disarticulation and was discharged on antibiotics. At follow-up,
      she had significantly reduced pain. Although vascular complications from
      orthopedic procedures are well described, this case seems to have been caused by
      secondary infection of her iatrogenic external iliac artery pseudoaneurysm.

PMID- 27890842
TI  - Treatment of a Patient with Abdominal Aortic Aneurysm and Hepatocellular
      Carcinoma.
AB  - BACKGROUND: The surgical tactics in cases of abdominal aortic aneurysms (AAA) and
      intra-abdominal malignancy are not uniform in the literature and are still a
      matter of debate. In this case report, we present a patient with coexisting AAA
      and primary liver cancer managed by simultaneous open AAA repair and liver
      resection After laparotomy and intraoperative liver ultrasonography that
      confirmed resectability of the tumor, aneurysm repair was performed with aorto
      aortic tube grafting after interrenal cross-clamping Radiofrequency-assisted
      liver transection was performed to complete an anterior anatomic resection of
      liver segments VI and VII. The postoperative course was uneventful and the
      patient was discharged on a postoperative day 10. METHODS: This was prospective
      follow up of one patient. RESULTS: The patient is free from disease at 18-month
      follow-up. CONCLUSIONS: The best treatment strategy for patients with AAA and
      malignant disease is still not clearly defined. Strategy selection is made
      individually according to the risk of rupture of AAA, general condition of the
      patient, experience of the teams that should perform the procedure and estimated
      life expectancy after resection of malignant disease.

PMID- 27890841
TI  - Development of a Scoring System for the Prediction of Early Graft Failure after
      Peripheral Arterial Bypass Surgery.
AB  - BACKGROUND: An occluded lower limb arterial bypass is associated with poor
      prognosis for the limb. Currently, no risk assessment method to estimate the risk
      of early graft failure exists. Aim of this study was to investigate the effect of
      various potential factors on early graft failure of infrainguinal bypass surgery
      and to develop a risk-scoring model to predict it. METHODS: A prospective
      observational clinical study was performed. One hundred infrainguinal bypass
      procedures (60 autologous and 40 synthetic grafts), throughout a 3-year period
      were included. Nearly, 84 patients suffered by chronic limb ischemia, whereas 16
      by acute limb ischemia or popliteal aneurysm disease. Various possible factors
      including demographic data, atherosclerosis predisposing factors, and technical
      details of the procedure were examined as possible causes of early graft failure.
      Using a combination of univariable and multivariable analysis techniques, the
      most significant factors were extracted, and a simple predicting risk-scoring
      system of early graft failure was calculated. RESULTS: The overall early graft
      failure rate was 14%. The factors related to it at a statistically significant
      level, 0.05, were the female gender, a bypass performed after a previous
      ipsilateral lower limb angioplasty, a redo procedure on the same limb, and a
      distal anastomosis at an inframalleolar level (pedal bypass). After internal
      validation, the FARP2-predicting scoring system was formed as following: Female
      gender 1 point (F), bypass after a previous Angioplasty 1 point (A), Redo bypass
      1 point (R), and Pedal bypass 2 points (P2). An overall score equal or greater
      than 2, provided an early graft failure prediction with sensitivity of 100%,
      specificity 86%, positive predictive value 54%, and negative predictive value of
      100% (area under the receiver operator characteristic curve: 0.959). CONCLUSIONS:
      FARP2 is a simple scoring system for predicting early graft failure after an
      infrainguinal bypass procedure. Further external validation in larger populations
      is needed.

PMID- 27890843
TI  - Total Endovascular Aortic Repair in a Patient with Marfan Syndrome.
AB  - BACKGROUND: The aim of this study is to describe a total endovascular aortic
      repair with branched and fenestrated endografts in a young patient with Marfan
      syndrome and a chronic aortic dissection. Open surgery is the gold standard to
      treat aortic dissections in patients with aortic disease and Marfan syndrome.
      METHODS: In 2000, a 38-year-old man with Marfan syndrome underwent open ascending
      aorta repair for an acute type A aortic dissection. One year later, a redo
      sternotomy was performed for aortic valve replacement. In 2013, the patient
      presented with endocarditis and pulmonary infection, which necessitated
      tracheostomy and temporary dialysis. In 2014, the first stage of the endovascular
      repair was performed using an inner branched endograft to exclude a 77-mm distal
      arch and descending thoracic aortic aneurysm. In 2015, a 63-mm thoracoabdominal
      aortic aneurysm was excluded by implantation of a 4-fenestrated endograft. Follow
      up after both endovascular repairs was uneventful. RESULTS: Total aortic
      endovascular repair was successfully performed to treat a patient with arch and
      thoraco-abdominal aortic aneurysm associated with chronic aortic dissection and
      Marfan syndrome. The postoperative images confirmed patency of the endograft and
      its branches, and complete exclusion of the aortic false lumen. CONCLUSIONS:
      Endovascular repair is a treatment option in patients with connective tissue
      disease who are not candidates for open surgery. Long-term follow-up is required
      to confirm these favorable early outcomes.

PMID- 27890844
TI  - Validation of a Decision Tree to Streamline Infrainguinal Vein Graft
      Surveillance.
AB  - BACKGROUND: Duplex ultrasound (DU)-based graft surveillance remains
      controversial. The aim of this study was to assess the ability of a recently
      proposed decision tree in identifying high-risk grafts which would benefit from
      DU-based surveillance. MATERIALS AND METHODS: Consecutive patients undergoing
      infrainguinal vein graft bypass from January 2008 to December 2015 were
      identified from the National Vascular registry and enrolled in a duplex
      surveillance program. An early postoperative DU was performed at a median of 6
      weeks (range: 4-9 weeks). Grafts were classified into high risk or low risk based
      on the findings of the earliest postoperative scan and 4 established risk factors
      for graft failure (diabetes, smoking, infragenicular distal anastomosis, and
      revision bypass surgery) using a classification and regression tree (CRT). The
      accuracy of the CRT model was evaluated using area under receiver operator
      characteristic (AROC) curve. RESULTS: About 278 vein graft bypasses were
      performed; 29 grafts had occluded by the first surveillance visit; 249 vein
      grafts were entered into surveillance. Sixty-four (23%) developed critical
      stenosis. Overall 30-month primary patency, primary-assisted patency, and
      secondary patency rates were 71.2%, 77.2%, and 80.1%, respectively. AROC for
      prediction of graft stenosis or occlusion was 83% (95% confidence interval [CI]:
      78-87%). The sensitivity and specificity of the CRT model for prediction of graft
      stenosis or occlusion were 95% (95% CI: 88-98%) and 52.2% (95% CI: 45-60%).
      CONCLUSIONS: A prediction model based on commonly recorded clinical variables and
      early postoperative DU scan is accurate at identifying grafts which are at high
      risk of failure. These high-risk grafts may benefit from DU-based surveillance.

PMID- 27890845
TI  - Physician-Modified C3 Excluder Endograft as the Preferred Solution to Treat a
      Juxtarenal Para-Anastomotic Aneurysm.
AB  - Feasibility and early satisfactory results of physician-modified endografts have
      been reported. Most reports described the use of Cook Dacron aortic endografts
      (Cook Medical, Inc., Bloomington, IN). However, in some specific anatomic
      features (short aortic length, narrow aorta), the use of this device may not be
      appropriate.We here report a case of juxtarenal aortic aneurysm proximal to a
      former aortobifemoral graft in a high surgical risk patient. Due to a narrow
      proximal neck and a short aortic length, a physician-modified Gore C3 Excluder
      device (W. L. Gore & Associates, Inc., Flagstaff, AR) incorporating a
      fenestration for a large accessory renal artery was implanted. At 6-month follow
      up, the aneurysm remains excluded and computed tomography scan demonstrates
      patent renal vessels.Surgeon-modified Gore C3 Excluder device implantation is
      feasible. Because of specific device characteristics (short main body,
      repositioning ability), it represents a valuable alternative in high-risk
      patients with juxtarenal aneurysms not amenable to other techniques.

PMID- 27890846
TI  - Successful Hybrid Treatment of a Traumatic Rupture of the Left Primitive Carotid
      Artery in a Polytraumatized Patient: A Case Report.
AB  - Traumatic injury of the left common carotid is a rare but severe disease, and is
      an uncommon situation in emergency units. Thoracic aortic lesions are often
      associated with other injuries, making their treatment challenging. We report the
      case of a successful hybrid approach to treat this lesion using a total supra
      aortic vessel debranching and a thoracic endovascular graft to cover the rupture,
      in a 38-year-old polytraumatized patient. After aortic, abdominal, and orthopedic
      surgery, the patient recovered well. The 1-year follow-up showed a good result of
      this hybrid treatment. This technique should be considered in polytraumatized
      patients with aortic arch lesions.

PMID- 27890847
TI  - Fenestrated and Branched Stent Grafting in Complex Aneurysmatic Aortic Disease: A
      Single-Center Early Experience.
AB  - BACKGROUND: The aim of this study is to present our early experience and
      highlight the technical difficulties associated with the use of fenestrated and
      branched stent grafts to treat patients with juxtarenal abdominal aortic aneurysm
      (AAA), pararenal AAA, and thoracoabdominal aortic aneurysms (TAAAs). METHODS: A
      prospectively held database maintained at our department was queried for patients
      who have undergone branched and fenestrated stent grafting for AAA or TAAA
      treatment. Indication for repair, comorbidity precluding open repair, technical
      challenges associated with the repair, as well as operative mortality, morbidity,
      and reintervention rate were evaluated. RESULTS: A total of 8 patients underwent
      repair with a fenestrated or branched stent graft. All patients had aneurysmal
      degeneration of the juxtarenal aorta, pararenal aorta, and thoracoabdominal aorta
      not suitable to standard endovascular techniques. Two patients had a prior aortic
      repair, a failed migrated stent graft, and an old surgical tube graft after an
      open repair. One patient had a type III TAAA and 1 patient had a postdissection
      TAAA type I. For all patients, target vessel success rate was 96.4% (27/28) and
      mean hospital stay was 6.0 days (range 3-21). Thirty-day and 1-year mortality
      were 0%. Mean follow-up was 23 months (range 7-45). Two endoleaks occurred, 1
      type III and 1 type II, which were treated endovascularly. No death or major
      complication occurred during follow-up. CONCLUSIONS: Fenestrated and branched
      endovascular stent grafts can be used to repair juxtarenal AAA, pararenal AAA,
      and TAAA in patients with significant comorbidities. However, several technical
      challenges have to be overcome due to the unique complex aortic pathology of each
      patient.

PMID- 27890849
TI  - Hybrid Treatment of a Suprarenal Aortic Aneurysm with an Infrarenal
      Aortobifemoral Surgical Graft and a Fenestrated Stent Graft.
AB  - BACKGROUND: The aim of this study was to report a hybrid technique for the
      treatment of a suprarenal aortic aneurysm (SAA) in a patient with iliac occlusive
      disease. Initially, an infrarenal aortobifemoral surgical graft was implanted,
      followed by deployment of a fenestrated bifurcated stent graft at the suprarenal
      part of the aorta. METHODS: A 69-year-old man presented with a 51-mm saccular
      suprarenal aortic aneurysm and iliac occlusive disease with intermittent
      claudication. Both common iliac arteries had been previously treated with kissing
      stents. Both external iliac arteries were severely stenosed precluding a total
      endovascular approach. RESULTS: The patient was treated with an infrarenal
      aortobifemoral surgical graft, facilitating the implantation of a custom-made
      fenestrated stent graft with fenestrations for the renal arteries and the
      superior mesenteric artery and a scallop for the celiac artery. The procedure was
      uneventful. Postoperative computed tomography angiography confirmed complete
      exclusion of the aneurysm and patent target vessels. Postoperatively, the patient
      did not report claudication symptoms anymore. CONCLUSIONS: A hybrid approach is a
      viable alternative to treat patients with complex aortic aneurysms and
      simultaneous peripheral occlusive disease, otherwise excluded from fenestrated
      stent grafting due to unsuitable access vessels.

PMID- 27890848
TI  - Postmarket Clinical Experience with the INCRAFT AAA Stent Graft System for
      Challenging Access Routes.
AB  - BACKGROUND: The INCRAFT system is a new device that has become available in
      Europe in September 2014 after the announcement of the 2-year results of the
      INNOVATION trial. However, no data in the "real-world" practice exist. Herein, we
      report our early series of consecutive patients treated with the INCRAFT after
      its launch on the market. METHODS: Prospectively collected data of patients
      enrolled in the INNOVATION trial (group IT) and consecutive patients from CE Mark
      approval to April 2015 (group CM) were retrospectively evaluated and compared.
      Main outcomes were any device- or procedure-related major adverse event (MAE)
      within 30 days and survival and reinterventions during follow-up. RESULTS:
      Seventeen patients were included in group IT (median follow-up [95% CI]; 60.4
      months [55-63]), and 24 patients were in group CM (12.5 [6.6-13.5]). The
      patients' comorbidities were comparable between the groups. The average diameter
      of aortic bifurcation and the bilateral external iliac arteries was significantly
      smaller in group CM. Adjunctive interventions for iliac artery disease were
      performed in 8 patients (33%) in group CM, whereas no adjunctive was required in
      group IT. MAEs within 30 days were not significantly different between 2 groups.
      Survival and reintervention rates were also equivalent after a median follow-up
      of 13 months. CONCLUSIONS: Compared to our patients recruited for the INNOVATION
      trial, the patients after CE Mark approval had significantly more challenging
      access routes reflecting the difficulties of "real-world" conditions. Despite
      frequent adjunctive procedures in group CM, the early performance of the
      endograft was encouraging so far. Long-term surveillance of those patients
      remains mandatory.

PMID- 27890850
TI  - Cheyne-Stokes respiration: Implications for anaesthesiologists.

PMID- 27890851
TI  - Protective ventilation during cardiac surgery: More than tidal volume?

PMID- 27890852
TI  - Adenocarcinoma Arising From an End Ileostomy in a Patient With Familial
      Adenomatous Polyposis.

PMID- 27890853
TI  - Chromoendoscopy for Surveillance in Ulcerative Colitis and Crohn's Disease: A
      Systematic Review of Randomized Trials.
AB  - BACKGROUND & AIMS: Key international guideline agencies recommend dysplasia
      surveillance in inflammatory bowel diseases with chromoendoscopy. We performed a
      systematic review of randomized trials comparing chromoendoscopy vs other
      endoscopic techniques for dysplasia surveillance in inflammatory bowel diseases.
      METHODS: We searched MEDLINE, EMBASE, and the Cochrane Central Register of
      Controlled Trials for relevant studies published through September 2016. We
      estimated risk ratios (RRs) for dichotomous outcomes (all-cause/colorectal cancer
      related mortality, time to interval cancer, patients with dysplasia,
      total/subtypes of dysplastic lesions, dysplasia detected by targeted biopsies,
      adverse events), mean differences for continuous outcomes (procedural time,
      costs, total/targeted biopsies), and their 95% confidence intervals (CIs) using a
      random-effects model. Subgroup analyses included technique compared with
      chromoendoscopy, type of disease, and type of dye. We estimated sensitivity and
      specificity of the techniques with reference to histology. RESULTS: We identified
      10 randomized trials (n = 1500 participants). There was a higher likelihood of
      detecting patients with dysplasia with chromoendoscopy compared with other
      techniques (RR, 1.37; 95% CI, 1.04-1.79). Subgroup analyses confirmed this effect
      only if chromoendoscopy was compared with standard-definition white-light
      endoscopy (RR, 2.12; 95% CI, 1.15-3.91). Chromoendoscopy required a significantly
      longer procedural time compared with other techniques (mean difference, 8.91 min;
      95% CI, 1.37-16.45). There was no difference in the likelihood of detecting
      dysplastic subtypes and dysplasia by targeted biopsies between groups. Test
      sensitivity and specificity were similar between groups. CONCLUSIONS: In
      surveillance of inflammatory bowel diseases, chromoendoscopy identifies more
      patients with dysplasia only when compared with standard-definition white-light
      endoscopy. It is associated with longer procedural time with no direct evidence
      of effect on preventing all-cause/cancer-specific mortality or time to interval
      cancer.

PMID- 27890854
TI  - Association Between Low Trough Levels of Vedolizumab During Induction Therapy for
      Inflammatory Bowel Diseases and Need for Additional Doses Within 6 Months.
AB  - BACKGROUND & AIMS: We investigated whether serum trough levels of vedolizumab, a
      humanized monoclonal antibody against integrin alpha4beta7, during the induction
      phase of treatment can determine whether patients will need additional doses
      (optimization of therapy) within the first 6 months. METHODS: We conducted an
      observational study of 47 consecutive patients with Crohn's disease (CD; n = 31)
      or ulcerative colitis (UC; n = 16) who had not responded to 2 previous treatment
      regimens with antagonists of tumor necrosis factor and were starting therapy with
      vedolizumab at 2 hospitals in France, from June 2014 through April 2016. All
      patients were given a 300-mg infusion of vedolizumab at the start of the study,
      Week 2, Week 6, and then every 8 weeks; patients were also given corticosteroids
      during the first 4-6 weeks. Patients not in remission at Week 6 were given
      additional doses of vedolizumab at Week 10 and then every 4 weeks (extended
      therapy or optimization). Remission at Week 6 of treatment was defined as CD
      activity score below 150 points for patients with CD and a partial Mayo Clinic
      score of <3 points, without concomitant corticosteroids, for patients with UC.
      Blood samples were collected each week and serum levels of vedolizumab and
      antibodies against vedolizumab were measured using an enzyme-linked immunosorbent
      assay. Median trough levels of vedolizumab and interquartile ranges were compared
      using the nonparametric Mann-Whitney test. The primary objective was to determine
      whether trough levels of vedolizumab measured during the first 6 weeks of
      induction therapy associated with the need for extended treatment within the
      first 6 months. RESULTS: Based on response to therapy at Week 6, extended
      treatment was required for 30 of the 47 patients (23 patients with CD and 7
      patients with UC). At Week 2, trough levels of vedolizumab for patients selected
      for extended treatment were 23.0 MUg/mL (interquartile range, 14.0-37.0 MUg/mL),
      compared with 42.5 MUg/mL in patients who did not receive extended treatment
      (interquartile range, 33.5-50.7; P = .15). At Week 6, trough levels of
      vedolizumab <18.5 MUg/mL were associated with need for extended therapy (100%
      positive predictive value, 46.2%; negative predictive value; area under the
      receiver operating characteristic curve, 0.72) within the first 6 months. Among
      patients who required extended treatment at Week 10, all of those with trough
      levels of vedolizumab <19.0 MUg/mL at Week 6 had achieved clinical remission 4
      weeks later (secondary responders). CONCLUSIONS: In a prospective study of
      patients with CD or UC receiving induction therapy with vedolizumab, low trough
      levels of vedolizumab at Week 6 (<19.0 MUg/mL) are associated with need for
      additional doses (given at Week 10 and then every 4 weeks). All patients
      receiving these additional doses achieved a clinical response 4 weeks later.

PMID- 27890855
TI  - Linker stability influences the anti-tumor activity of acetazolamide-drug
      conjugates for the therapy of renal cell carcinoma.
AB  - Small molecule-drug conjugates (SMDCs) are increasingly being considered as an
      alternative to antibody-drug conjugates (ADCs) for the selective delivery of
      anticancer agents to the tumor site, sparing normal tissues. Carbonic anhydrase
      IX (CAIX) is a membrane-bound enzyme, which is over-expressed in the majority of
      renal cell carcinomas and which can be efficiently targeted in vivo, using
      charged derivatives of acetazolamide, a small heteroaromatic sulfonamide. Here,
      we show that SMDC products, obtained by the coupling of acetazolamide with
      monomethyl auristatin E (MMAE) using dipeptide linkers, display a potent anti
      tumoral activity in mice bearing xenografted SKRC-52 renal cell carcinomas. A
      comparative evaluation of four dipeptides revealed that SMDCs featuring valine
      citrulline and valine-alanine linkers exhibited greater serum stability and
      superior therapeutic activity, compared to the counterparts with valine-lysine or
      valine-arginine linkers. The most active products substantially inhibited tumor
      growth over a prolonged period of time, in a tumor model for which sunitinib and
      sorafenib do not display therapeutic activity. However, complete tumor
      eradication was not possible even after ten intravenous injection. Macroscopic
      near-infrared imaging procedures confirmed that ligands had not lost the ability
      to selectively localize at the tumor site at the end of therapy and that the
      neoplastic masses continued to express CAIX. The findings are of mechanistic and
      of therapeutic significance, since CAIX is a non-internalizing membrane
      associated antigen, which can be considered for targeted drug delivery
      applications in kidney cancer patients.

PMID- 27890856
TI  - siRNA-cell-penetrating peptides complexes as a combinatorial therapy against
      chronic myeloid leukemia using BV173 cell line as model.
AB  - Chronic myeloid leukemia (CML) is a myeloproliferative disorder caused by a
      single gene mutation, a reciprocal translocation that originates the Bcr-Abl gene
      with constitutive tyrosine kinase activity. As a monogenic disease, it is an
      optimum target for RNA silencing therapy. We developed a siRNA-based therapeutic
      approach in which the siRNA is delivered by pepM or pepR, two cell-penetrating
      peptides (CPPs) derived from the dengue virus capsid protein. These peptides have
      a dual role: siRNA delivery into cells and direct action as bioportides, i.e.
      intracellularly bioactive CPPs, targetting cancer-related signaling processes.
      Both pepM and pepR penetrate the positive Bcr-Abl+ Cell Line (BV173). Five in
      silico designed anti-Bcr-Abl siRNA were selected for in vitro analysis after
      thorough screening. The Bcr-Abl downregulation kinetics (48h to 168h) was
      followed by quantitative PCR. The bioportide action of the peptide vectors was
      evaluated by genome-wide microarray analysis and further validated by testing
      BV173 cell cycle and cell proliferation monitoring different genes involved in
      housekeeping/cell stress (RPL13A, HPRT1), cell proliferation (ki67), cell
      apoptosis (Caspase 3 and Caspase 9) and cell cycle steps (CDK2, CCDN2, CDKN1A).
      Assays with a commercial transfection agent were carried out for comparison
      purposes. Maximal Bcr-Abl gene knockdown was observed for one of the siRNA when
      delivered by pepM at 120h. Both pepM and pepR showed downregulation effects on
      proliferative CML-related signaling pathways having direct impact on BV173 cell
      cycle and proliferation, thus reinforcing the siRNA effect by acting as
      anticancer molecules. With this work we show the therapeutic potential of a CPP
      shuttle that combines intrinsic anticancer properties with the ability to deliver
      functional siRNA into CML cell models. By such combination, the pepM-siRNA
      conjugates lowered Bcr-Abl gene expression levels more extensively than
      conventional siRNA delivery technologies and perturbed leukemogenic cell
      homeostasis, hence revealing their potential as novel alternative scaffolds for
      CML therapy.

PMID- 27890857
TI  - Structural insights into a family 39 glycoside hydrolase from the gut symbiont
      Bacteroides cellulosilyticus WH2.
AB  - Bacteria from the human gut are equipped with an arsenal of carbohydrate-active
      enzymes that degrade dietary and host-derived glycans. In this study, we present
      the 2.5A resolution crystal structure of a member (GH39wh2) from the human gut
      bacteria Bacteroides cellulosilyticus WH2 representative of a new subgroup within
      family GH39. Together with 6 other GHs, GH39wh2 belongs to a polysaccharide
      utilization locus (PUL) that could be involved in detecting, binding and
      hydrolysing a specific carbohydrate species from the intestinal tract. GH39wh2
      shares a similar architecture as other members of family GH39 dominated by a
      typical (beta/alpha)8-barrel fold harboring the catalytic residues and decorated
      by beta-sandwich accessory domains. The GH39wh2 structure unveils an atypical
      shallow groove rather than a deep pocket due to drastic rearrangements in surface
      loops surrounding the catalytic interface. These structural adaptations seem to
      favour recognition of large branched substrates and may explain the lack of
      activity of GH39wh2 toward small xylose-based and other typical substrates from
      GH39 members, emphasizing the molecular diversity within the GH39 family. A
      phylogenetic analysis of the entire GH39 family assigns GH39wh2 as a new
      subgroup, consistent with the extensive remodelling of the active site region
      that may confer new substrate specificity toward a complex glycan chain.

PMID- 27890858
TI  - Predictors and outcome of acute kidney injury after transcatheter aortic valve
      implantation: a systematic review and meta-analysis.
AB  - AIMS: The aim of this systematic review and meta-analysis was to investigate the
      predictors and outcome of acute kidney injury (AKI) after transcatheter aortic
      valve implantation (TAVI). METHODS AND RESULTS: There were 35 articles recruiting
      13,256 patients included in our study. Hypertension (odds ratio [OR] 1.92, 95%
      CI: 1.44 to 2.56), diabetes mellitus (OR 1.33, 95% CI: 1.20 to 1.47), peripheral
      artery disease (OR 1.28, 95% CI: 1.14 to 1.45) and a left ventricular ejection
      fraction <40% (OR 1.50, 95% CI: 1.19 to 1.88) were identified as significant
      independent predictors of AKI. In addition to the aforementioned comorbidities,
      procedure-related/post-TAVI factors such as transapical access (OR 1.68, 95% CI:
      1.44 to 1.97), major bleeding (OR 1.82, 95% CI: 1.37 to 2.40) and transfusion (OR
      1.30, 95% CI: 1.12 to 1.51) were also associated with a higher risk of AKI.
      Importantly, the risk of short-term all-cause death increased progressively with
      the aggravating severity of AKI (OR, 30 days: stage 1: 3.41; stage 2: 4.0; stage
      3: 11.02; one year: stage 1: 1.95; stage 2: 2.82; stage 3: 7.34), as determined
      by a univariate analysis. After eliminating confounders, AKI remained linked to a
      higher risk for both short-term (30 days: HR 2.12, 95% CI: 1.59 to 2.83) and long
      term (>=3 years: HR 1.37, 95% CI: 1.27 to 1.48) all-cause mortality. CONCLUSIONS:
      The reason for the occurrence of AKI was multifactorial, including baseline
      characteristics, procedure-related and post-TAVI factors. It appeared that even
      stage 1 AKI exerted detrimental effects on survival within one year, and AKI was
      also independently linked to mortality beyond three years.

PMID- 27890859
TI  - Chronic total coronary occlusion treated by percutaneous coronary intervention:
      long-term outcome in patients with and without diabetes.
AB  - AIMS: Despite technical advancements, long-term outcomes after chronic total
      occlusion (CTO) recanalisation remain a subject of debate, especially in diabetic
      patients. The aim of this study, therefore, was to assess the very long-term
      clinical outcome of diabetic vs. non-diabetic patients in a large cohort from a
      high-volume CTO PCI centre according to whether or not CTO recanalisation had
      been successfully achieved. METHODS AND RESULTS: Between 2004 and 2012, 1,320
      consecutive patients underwent PCI for CTO, 27.4% (362/1320) of whom were
      diabetics. We compared cardiac death, target lesion revascularisation (TLR),
      myocardial infarction (MI) and combined major adverse cardiac events (MACE) in
      patients with successful versus failed PCI (median follow-up 4.2 years). The PCI
      success rate was 75% (990/1,320 patients), with no significant differences
      between diabetics and non-diabetics (69.8% vs. 75%, respectively, p=0.07).
      Successful recanalisation was associated with lower cardiac death rates (13.2%
      vs. 17.2%, respectively, p<0.001) and lower MACE (27.5% vs. 33.7%, respectively,
      p=0.02). There were no significant differences in TLR (8.9% vs. 14.2% for failed
      recanalisation, p=0.29) and MI (4.7% vs. 10% for failed recanalisation).
      Successful recanalisation was a predictor of survival (HR 0.5, 95% CI: 0.32-0.81,
      p=0.005), whereas diabetes (HR 2.44, 95% CI: 1.52-3.83, p<0,001), left
      ventricular ejection fraction (HR 0.96, 95% CI: 0.94-0.99, p=0.004) and age (HR
      1.06, 95% CI: 1.03-1.08, per year increment, p<0.0001) were predictors of cardiac
      death at follow-up. Cardiac mortality rates varied markedly after failed PCI
      between diabetic (20/103, 24.7%) and non-diabetic patients (15/227, 9.3%,
      p<0.0001 for comparison between groups), suggesting an interaction between the
      presence of diabetes and procedural outcome. CONCLUSIONS: CTO recanalisation was
      associated with improved long-term survival, a reduced rate of MACE for up to
      nine years, and suggests a greater reduction in cardiac death among diabetic
      patients.

PMID- 27890860
TI  - Renal denervation by CT-guided periarterial injection of hyperosmolar saline,
      vincristine, paclitaxel and guanethidine in a pig model.
AB  - AIMS: The aim of the study was to evaluate the feasibility, safety and efficacy
      of renal sympathetic denervation with CT-guided periarterial injection of
      potentially neurolytic agents in pigs. METHODS AND RESULTS: Unilateral injection
      of formulations containing either 5M hyperosmolar saline, vincristine, paclitaxel
      or guanethidine around the renal artery was performed in 24 normotensive pigs
      with six animals per group. Needle placement and injections were performed under
      CT fluoroscopy guidance. Blood pressure measurements and CT scans were performed
      immediately before and after the intervention and four weeks after treatment.
      After euthanasia, norepinephrine (NE) concentrations of both kidneys were
      determined. The renal arteries and surrounding tissue were examined
      histologically to evaluate nerve fibre degeneration. Procedures were technically
      successful with good periarterial distribution of the injectant in all but one
      pig in the guanethidine group. No major adverse events or post-interventional
      complications occurred. In the vincristine group, NE concentrations of the renal
      parenchyma were lower on the treated side in all pigs with a mean decrease of 53%
      (38%-62%, p<0.01) compared to the contralateral control. Correspondingly,
      histological examination revealed neural degeneration in all animals treated with
      vincristine. In the other groups, no significant drop of NE values, or
      histological signs of nerve fibre degeneration were found. CONCLUSIONS: CT-guided
      periarterial injection of the different substances was feasible and safe. Renal
      sympathetic denervation was achieved with vincristine. In contrast, hyperosmolar
      saline, paclitaxel and guanethidine do not seem to be appropriate for renal
      denervation in a pig model at the dosage used.

PMID- 27890861
TI  - Computed tomography angiography planning identifies the target vessel for optimum
      infarct location and improves clinical outcome in alcohol septal ablation for
      hypertrophic obstructive cardiomyopathy.
AB  - AIMS: Alcohol septal ablation (ASA) is an established treatment option in
      hypertrophic obstructive cardiomyopathy (HOCM). ASA is ineffective in some:
      inaccurate infarct and inability to identify a vessel contribute. We aimed to
      improve accuracy of infarct using CT angiography guidance and provide a more
      predictable and satisfactory outcome. METHODS AND RESULTS: Twenty-one successive
      patients with symptomatic LVOT obstruction refractory to medication underwent CT
      angiography planning to guide ASA. CT was performed using a dual-source CT
      system. Alcohol was delivered to the artery identified from CT: in 17/21 this was
      a sub-branch of a septal artery, in 2/21 the septal vessel was identified from
      the circumflex artery. Peak gradient improved from 98 (IQR 89.50-111.50) mmHg to
      14 (IQR 8.50-22) mmHg (p=0.003). Systolic anterior motion (SAM) improved in 18/20
      patients. NYHA class improved by >=1 in 18/20. Peak VO2 improved from 79.19% of
      predicted value (+/-14.01) to 91.62% (+/-12.02) predicted (p<0.0001). Success at
      the first procedure is greater with CT guidance, 17/20 vs. 50/75 with traditional
      methods (pre-CT guidance) (p=0.02); 9/20 had six-month CMR with target septum
      infarct in all. ASA-related RBBB reduced from 62% to 13% (p=0.0004). CONCLUSIONS:
      CT angiography planning improves localisation of infarct and procedural success
      at the first attempt in ASA when compared to traditional methods. Follow-up to
      six months suggests a symptomatic, functional and haemodynamic improvement.

PMID- 27890862
TI  - Randomised, blinded and controlled comparative study of chemical and
      radiofrequency-based renal denervation in a porcine model.
AB  - AIMS: The blood pressure-lowering effect of percutaneous renal denervation (RDN)
      is controversial. The success of RDN may be device-dependent. We sought to
      compare the efficacy of RDN by chemical neurolysis using alcohol (Peregrine
      System Infusion Catheter; Ablative Solutions, Inc., Menlo Park, CA, USA) to RDN
      by radiofrequency (RF) ablation with the single-electrode RF catheter (Symplicity
      Flex; Medtronic, Minneapolis, MN, USA) in a porcine model. METHODS AND RESULTS:
      This was a prospective, randomised, blinded study. Pigs were assigned to undergo
      bilateral RF ablation or chemical neurolysis. Primary endpoints were ablation
      depth and renal tissue norepinephrine (NE) concentrations at three-month follow
      up. Twelve pigs underwent RF ablation (n=4) or chemical neurolysis by infusion of
      0.3 mL (n=4) or 0.6 mL (n=4) alcohol. Ninety days after RF ablation and chemical
      neurolysis with 0.3 mL and 0.6 mL of alcohol, mean maximal tissue injury depth
      was 3.9+/-1.2 mm, 6.6+/-1.7 mm and 8.2+/-2.2 mm, respectively (p<0.001 for either
      dose of alcohol vs. RF ablation). Compared with historical controls, median renal
      tissue NE concentration reductions were 66%, 78% and 83% after RF ablation and
      chemical neurolysis using 0.3 mL and 0.6 mL alcohol, respectively (p=0.107 for
      chemical neurolysis vs. RF ablation). Mean total ablation area was significantly
      greater in both (0.3 mL and 0.6 mL) alcohol groups (p=0.0001 for both) than the
      RF ablation group (30.8+/-13.7 mm2, 41.6+/-12.4 mm2 and 11.0+/-7.5 mm2,
      respectively). CONCLUSIONS: RDN is more effective using chemical neurolysis than
      single-electrode RF ablation. Our findings suggest that the efficacy of RDN may
      be device-dependent.

PMID- 27890863
TI  - The first clinical experience with a novel "locking" microcatheter in chronic
      coronary total occlusions.
AB  - AIMS: A novel "locking" microcatheter has been developed to address residual
      failure modes in chronic total occlusion (CTO) percutaneous coronary intervention
      (PCI). The aim of this study was to report the first clinical experience of this
      device. METHODS AND RESULTS: The microcatheter was assessed prospectively in 92
      unselected CTO cases across six European sites. Overall technical success was
      85.9% (79/92) and 97.5% for patients with a J-CTO score of <3 (39/40). Within-CTO
      tortuosity was the only lesion characteristic to predict reduced technical
      success (OR 0.10 [0.01-0.97], p=0.047). Calcification (OR 0.45 [0.04-5.31],
      p=0.53), lesion length >20 mm (OR 0.58 [0.05-6.81], p=0.66) and a blunt proximal
      cap (OR 0.47 [0.08-2.90], p=0.42) were not associated with technical failure in
      this case series. Locking facilitated guidewire crossing (after initial failure)
      of the proximal cap in 23 cases, distal cap in 11 cases and CTO body in 10 cases,
      and delivery of the microcatheter through to the distal vessel in 22 cases. The
      overall procedural complication rate was 1.1% (1/92) with no major events.
      CONCLUSIONS: Guidewire locking with this novel microcatheter assists penetration
      and crossing of fibrocalcific anatomy with a high degree of safety. Using this
      device in CTO PCI may lead to improved primary wiring and overall procedural
      success rates.

PMID- 27890864
TI  - Lack of evidence for interventions offered in UK fertility centres.

PMID- 27890865
TI  - CSF-PR 2.0: An Interactive Literature Guide to Quantitative Cerebrospinal Fluid
      Mass Spectrometry Data from Neurodegenerative Disorders.
AB  - The rapidly growing number of biomedical studies supported by mass spectrometry
      based quantitative proteomics data has made it increasingly difficult to obtain
      an overview of the current status of the research field. A better way of
      organizing the biomedical proteomics information from these studies and making it
      available to the research community is therefore called for. In the presented
      work, we have investigated scientific publications describing the analysis of the
      cerebrospinal fluid proteome in relation to multiple sclerosis, Parkinson's
      disease and Alzheimer's disease. Based on a detailed set of filtering criteria we
      extracted 85 data sets containing quantitative information for close to 2000
      proteins. This information was made available in CSF-PR 2.0
      (http://probe.uib.no/csf-pr-2.0), which includes novel approaches for filtering,
      visualizing and comparing quantitative proteomics information in an interactive
      and user-friendly environment. CSF-PR 2.0 will be an invaluable resource for
      anyone interested in quantitative proteomics on cerebrospinal fluid.

PMID- 27890866
TI  - Claims for fertility interventions: a systematic assessment of statements on UK
      fertility centre websites.
AB  - OBJECTIVES: Fertility services in the UK are offered by over 200 Human
      Fertilisation and Embryology Authority (HFEA)-registered NHS and private clinics.
      While in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)
      form part of the National Institute for Health and Care Excellence (NICE)
      guidance, many further interventions are offered. We aimed to record claims of
      benefit for interventions offered by fertility centres via information on the
      centres' websites and record what evidence was cited for these claims. METHODS:
      We obtained from HFEA a list of all UK centres providing fertility treatments and
      examined their websites. We listed fertility interventions offered in addition to
      standard IVF and ICSI and recorded statements about interventions that claimed or
      implied improvements in fertility in healthy women. We recorded which claims were
      quantified, and the evidence cited in support of the claims. Two reviewers
      extracted data from websites. We accessed websites from 21 December 2015 to 31
      March 2016. RESULTS: We found 233 websites for HFEA-registered fertility
      treatment centres, of which 152 (65%) were excluded as duplicates or satellite
      centres, 2 were andrology clinics and 5 were unavailable or under construction
      websites. In total, 74 fertility centre websites, incorporating 1401 web pages,
      were examined for claims. We found 276 claims of benefit relating to 41 different
      fertility interventions made by 60 of the 74 centres (median 3 per website; range
      0 to 10). Quantification was given for 79 (29%) of the claims. 16 published
      references were cited 21 times on 13 of the 74 websites. CONCLUSIONS: Many
      fertility centres in the UK offer a range of treatments in addition to standard
      IVF procedures, and for many of these interventions claims of benefit are made.
      In most cases, the claims are not quantified and evidence is not cited to support
      the claims. There is a need for more information on interventions to be made
      available by fertility centres, to support well-informed treatment decisions.

PMID- 27890868
TI  - Serological validation of an alveolar echinococcosis rat model with a single
      hepatic lesion.
AB  - Serology is important for the diagnosis and follow-up of human alveolar
      echinococcosis (AE). However, patient conditions are highly variable among those
      with AE, and antibody responses in serological follow-up have not been well
      defined. We recently described a new AE rat model established by implantation of
      small AE tissue into a single arbitrary location in the liver; no metastasis and
      dissemination were observed. In the present study, we examined the serological
      characteristics in our rat model before and after surgical treatment. The results
      showed that antibody responses against crude antigens were increased at one month
      after transplantation and similar to those of other model animals. For the
      antigen Em18, antibody responses were slower in our rat model than in other
      animal models. After surgical resection, changes in antibody responses against
      Em18 were similar to those observed in human patients with AE. Because of the
      slow growth of lesions, establishment of a single hepatic lesion and patterns of
      antibody responses, our rat model may be useful for clarifying follow-up
      serodiagnoses in human AE and determining the mechanisms of multi-organ
      involvement by primary infection with oncospheres rather than metastasis.

PMID- 27890870
TI  - Improving the Quality of Postgraduate Education in Traditional Japanese Kampo
      Medicine for Junior Residents: An Exploratory Survey Conducted in Five
      Institutions in the Tohoku Area.
AB  - Traditional Japanese (Kampo) medicine has been widely applied in general medicine
      in Japan. In 2001, the model core curriculum for Japanese medical education was
      revised to include Kampo medicine. Since 2007, all 80 Japanese medical schools
      have incorporated it within their programs. However, postgraduate training or
      instruction of Kampo medicine has not been recognized as a goal for the clinical
      training of junior residents by Japan's Ministry of Health, Labour and Welfare;
      little is known about postgraduate Kampo medicine education. This exploratory
      study investigated attitudes about Kampo medicine among junior residents in
      Japanese postgraduate training programs. A questionnaire survey was administered
      to junior residents at five institutions in the Tohoku area of Japan. Questions
      evaluated residents' experiences of prescribing Kampo medicines and their
      expectations for postgraduate Kampo education and training. As a result, 121
      residents responded (response rate = 74%). About 96% of participants had
      previously received Kampo medicine education at their pre-graduate medical
      schools and 64% had prescribed Kampo medications. Specifically, daikenchuto was
      prescribed to prevent ileus and constipation after abdominal surgery and
      yokukansan was prescribed to treat delirium in the elderly. Residents received on
      the-job instruction by attending doctors. Over 70% of participants indicated that
      there was a need for postgraduate Kampo medicine education opportunities and
      expected lectures and instruction on how to use it to treat common diseases. In
      conclusion, we have revealed that junior residents require Kampo medicine
      education in Japanese postgraduate training programs. The programs for
      comprehensive pre-graduate and postgraduate Kampo education are expected.

PMID- 27890867
TI  - Obesity-Related Digestive Diseases and Their Pathophysiology.
AB  - Obesity is a growing medical and public health problem worldwide. Many digestive
      diseases are related to obesity. In this article, the current state of our
      knowledge of obesity-related digestive diseases, their pathogenesis, and the
      medical and metabolic consequences of weight reduction are discussed. Obesity
      related digestive diseases include gastroesophageal reflux disease, Barrett's
      esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver
      disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone,
      cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal
      diseases are associated with altered mechanical and humoral factors, other
      obesity-related digestive diseases seem to be associated with obesity-induced
      altered circulating levels of adipocytokines and insulin resistance. The
      relationship between functional gastrointestinal disease and obesity has been
      debated. This review provides a comprehensive evaluation of the obesity-related
      digestive diseases, including pathophysiology, obesity-related risk, and medical
      and metabolic effects of weight reduction in obese subjects.

PMID- 27890869
TI  - An improved Red/ET recombineering system and mouse ES cells culture conditions
      for the generation of targeted mutant mice.
AB  - Targeted mutant mice generated on a C57BL/6 background are powerful tools for
      analysis of the biological functions of genes, and gene targeting technologies
      using mouse embryonic stem (ES) cells have been used to generate such mice.
      Recently, a bacterial artificial chromosome (BAC) recombineering system was
      established for the construction of targeting vectors. However, gene retrieval
      from BACs for the generation of gene targeting vectors using this system remains
      difficult. Even when construction of a gene targeting vector is successful, the
      efficiency of production of targeted mutant mice from ES cells derived from
      C57BL/6 mice are poor. Therefore, in this study, we first improved the strategy
      for the retrieval of genes from BACs and their transfer into a DT-A plasmid, for
      the generation of gene targeting vectors using the BAC recombineering system.
      Then, we attempted to generate targeted mutant mice from ES cell lines derived
      from C57BL/6 mice, by culturing in serum-free medium. In conclusion, we
      established an improved strategy for the efficient generation of targeted mutant
      mice on a C57BL/6 background, which are useful for the in vivo analysis of gene
      functions and regulation.

PMID- 27890871
TI  - Chagas Disease in Mexico: Report of 14 Cases of Chagasic Cardiomyopathy in
      Children.
AB  - Chagas disease is a parasitic infection mainly found in Latin America; it is
      transmitted by a triatomine, also known as assassin bug or kissing bug. In
      humans, the parasite causes mostly cardiac disorders. Two-thirds of the Mexican
      territory are regarded as risk areas for vector transmission of Trypanosoma
      cruzi, the causal agent. The parasite can be found as a blood-borne
      trypomastigote or as an intracellular amastigote. The progression and severity of
      lesions could be due to frequent reinfections or to infection by highly virulent
      strains. A total of 3,327 individuals younger than 18 years old, living in risk
      areas for this disease in the rural setting of the States of Queretaro, San Luis
      Potosi, and Veracruz, underwent a seroepidemiological study. Among them, 37
      subjects were seropositive for T. cruzi, and were studied to look for signs of
      cardiac pathology, which has only been reported in adults. A clinical record was
      prepared for all included individuals, and electrocardiography (ECG) and
      echocardiography (ECHO) studies were performed; 25 cases showed lesions
      compatible with the onset of Chagas cardiomyopathy. The other 12 patients showed
      either normal ECG and ECHO data or showed abnormal parameters that were not
      regarded as significant. Lesions found in the onset of Chagas cardiomyopathy in
      children are herein reported, along with 14 cases of cardiac pathology compatible
      with Chagas disease. Our results indicate that patients younger than 18 years can
      show a cardiac pathology similar to that observed in adults.

PMID- 27890872
TI  - Effect of astigmatism on refraction in children with high hyperopia.
AB  - The aim of this study was to evaluate primitively whether the extent and
      component of astigmatism influences regression in degree of spherical (DS) and
      the best corrected visual acuity (BCVA) of children with hyperopia of +5.00
      diopters (D) or greater. Children were screened from the outpatient refraction
      database in the Wenling No. 1 People's Hospital in Zhejiang province and in Eye &
      ENT Hospital of Fudan University between June 2005 and December 2015. Eligible
      eyes were divided into three groups according to the extent of astigmatism: group
      of astigmatism <= -2 D of cylinder, group without astigmatism or with astigmatism
      >= -0.5 D of cylinder, and the group with astigmatism >= -0.75 D and <= -1.75 D
      of cylinder. For the component of astigmatism, eyes with astigmatism as <= -0.75
      D of cylinder were divided into 3 groups: with the rule (WTR), against the rule
      (ATR) and the group with the oblique. Differences in the changes of BCVA and
      refractive error (RE) during follow-up terms were compared within and among
      groups. Differences in the mean DS or BCVA were not statistically significant
      between groups according to the extent of the astigmatism at the last visit (p =
      0.2396 and p = 0.2131, respectively). As for the component of astigmatism, the
      group with oblique astigmatism had more severe hyperopia than the group of WTR (p
      < 0.0001) and mean BCVA in the group of ATR were better than that of the other
      two groups (p < 0.0001) at the first visit. However, the among-group changes were
      not significant at the end of the observation (p > 0.1). The regression of DS and
      improvement of the BCVA in children with hyperopia of +5.00D or greater may be
      irrespective of the component and the extent of astigmatism.

PMID- 27890873
TI  - Overabundance of sika deer and immunocontraception.
AB  - The impact of deer overabundance is a worldwide problem. Along with habitat
      expansion and population increase, damage by sika deer to the forest ecosystem
      and agriculture has become a serious issue in Japan. Deer also transmit a number
      of diseases and parasites to humans and livestock. The overabundance of deer is a
      result of their strong fecundity, and therefore the present situation should, in
      theory, be tackled by experts in reproductive biology.

PMID- 27890874
TI  - Development of a lipopolysaccharide (LPS)-supplemented adjuvant and its effects
      on cell-mediated and humoral immune responses in male rats immunized against
      sperm.
AB  - Supplementation with lipopolysaccharide (LPS) from non-pathogenic Escherichia
      coli was found to enhance the adjuvant effects of a veterinary vaccine adjuvant
      (ISA 71VG(r)). Sperm immunization using 71VG as an adjuvant in the immature
      period induced infertility in 25% of male rats, whereas this increased to 62.5%
      after immunization with 71VG + LPS or Freund's complete adjuvant (FCA). Mean
      testicular weight of non-sterile males in the 71VG + LPS group was significantly
      lower than that in the 71VG or FCA group. Histological examination of testicular
      tissue from sterile males demonstrated severe impairment of spermatogenesis due
      to experimental autoimmune orchitis, a cell-mediated autoimmune condition. The
      serum anti-sperm titer was elevated in the three sperm-immunized groups relative
      to male rats treated with adjuvant alone, but the titer was higher in the 71VG +
      LPS and FCA groups than in the 71VG group. We consider that this LPS-supplemented
      adjuvant stimulates both humoral and cell-mediated immune responses to an extent
      comparable to FCA.

PMID- 27890875
TI  - Induction of apoptosis by ethanol extract of Evodia rutaecarpa in HeLa human
      cervical cancer cells via activation of AMP-activated protein kinase.
AB  - The fruit of Evodia rutaecarpa (Juss.) Benth has been used widely in traditional
      medicine therapy. Although it has been shown to possess many pharmacological
      activities, the molecular mechanisms of its anti-cancer activity have not been
      clearly elucidated. In the present study, we investigated the pro-apoptotic
      effects of an ethanol extract isolated from immature fruits of E. rutaecarpa
      (EEER) in HeLa human cervical cancer cells. EEER treatment decreased the cell
      viability of HeLa cells in a concentration-dependent manner, which was related to
      apoptotic cell death resulting from apoptotic body formation, DNA fragmentation,
      and an increased population of annexin V+-positive cells. EEER treatment
      significantly suppressed anti-apoptotic Bcl-2 expression, leading to subsequent
      loss of mitochondrial membrane potential (MMP), while it did not change
      expression levels of death receptor (DR)-related proteins. EEER treatment
      increased activity of caspase-3 and -9 but not caspase-8, and pretreatment of a
      caspase-3 inhibitor markedly attenuated EEER-induced apoptosis. Furthermore, EEER
      activated the AMP-activated protein kinase (AMPK) signaling pathway; however,
      inhibition of AMPK markedly abrogated EEER-induced apoptosis. Overall, the
      results suggest that the apoptotic activity of EEER may be associated with a
      caspase-dependent cascade through activation of the intrinsic signaling pathway
      connected with AMPK activation. E. rutaecarpa could be a prospective clinical
      application to treat human cervical cancer.

PMID- 27890876
TI  - Synthesis and Antifungal in Vitro Evaluation of Pyrazolo[3,4-b]pyridines
      Derivatives Obtained by Aza-Diels-Alder Reaction and Microwave Irradiation.
AB  - A series of pyrazolo[3,4-b]pyridines were prepared by a microwave-assisted aza
      Diels-Alder reaction between pyrazolylformimidamides 1 and beta-nitrostyrenes 2
      in toluene as the solvent. This procedure provides a simple one-step and
      environmentally friendly methodology with good yields for the synthesis of these
      compounds. All compounds were tested for antifungal activity against two
      clinically important fungi Candida albicans and Cryptococcus neoformans. Within
      the compounds of the series bearing a -CH3 group on the carbon C-3 of the azole
      ring (3a-e), the compound without a substituent on the p'-phenyl ring (3a),
      showed the best activity against both fungi, followed by the p'-Br-phenyl (3c).
      Within the compounds of the series bearing a tert-butyl group in the carbon C-3
      of the azole ring (3f-j), the non-substituted p'-compound (3f) was the most
      active one, followed by (3h) (p'-Br substituted) that showed the best activity
      against both fungi. The remaining compounds of this sub-series (3g, i, j) showed
      similar moderate activities. The antifungal activity of the compounds of the
      series was found to be correlated with a higher log P and a lower dipole moment
      in the more active compounds.

PMID- 27890877
TI  - Exploring the Multifunctionality of a Novel Long-Chain Amidoamine Amphiphile.
AB  - In this review, we demonstrate that the practical applications of a novel long
      chain amidoamine derivative with a simple molecular structure (C18AA) are
      equivalent to or higher in number than those of supramolecules with complex
      molecular structures. Molecular assemblies of C18AA exhibit distinctive thermal
      responsiveness; namely, C18AA can form a gel with apolar organic solvents, while
      O/W emulsions of C18AA act as a heat-induced gelator that undergoes a phase
      transition from solution to gel upon heating. We also show that C18AA emulsions
      containing a quaternary ammonium salt develop an iridescent color over a specific
      temperature range. Further, molecular assemblies of C18AA serve as high
      performance soft templates for the preparation of shape-controlled metal
      nanocrystals such as ultrathin Au nanowires and Pd nanowires.

PMID- 27890878
TI  - Prevalence of electrocardiographic abnormalities in patients with myasthenia
      gravis.
AB  - OBJECTIVE: Myasthenia gravis (MG) is an immunological disorder of the
      neuromuscular junction, characterized by easy fatigability and weakness of the
      skeletal muscles. However, it has sometimes been reported that heart diseases
      including cardiomyopathies leading to sudden death have been observed in patients
      with MG. We studied the prevalence of electrocardiographic (ECG) abnormalities
      and heart disease in patients newly diagnosed with MG who had not received
      immunotherapy. METHODS: Fifty-three patients with MG were enrolled in our study.
      We reviewed the ECG recordings of all patients on admission, and assessed the
      prevalence of ECG abnormalities and heart diseases associated with MG. RESULTS:
      Thirty-three (62.2%) patients had ECG abnormalities, including early
      repolarization (15 patients), negative T waves (9 patients), left ventricular
      hypertrophy (5 patients), and prolonged QTc (4 patients). A higher frequency of
      early repolarization was observed in patients with MG compared to healthy
      subjects. DISCUSSION: ECG abnormalities in patients with MG were more prevalent
      in our series than in the general population. This may be because of the
      increasing incidence of MG in the elderly. However, we also observed that younger
      patients developed severe heart disease, indicating the possibility of other
      mechanisms, such as the presence of antimyocardial antibodies. Clinicians should
      be aware of the complications of heart disease in patients with MG, especially
      during the perioperative period for thymectomy or thymomectomy.

PMID- 27890879
TI  - Egocentric disorientation and heading disorientation: evaluation by a new test
      named card placing test.
AB  - We recently developed a new clinical test named card placing test (CPT) which can
      assess a subject's ability to deal with visuospatial information. The CPT
      requires a subject to recreate an array of three cards, each of which was
      randomly placed on eight grids around the subject, before (CPT-A) and after the
      subject's rotation (CPT-B). With this design, the CPT can assess a subject's
      ability to represent visuospatial information either egocentrically (CPT-A) or
      allocentrically (CPT-B). We administered the test on two patients with
      topographical disorientation; one with egocentric disorientation and another with
      heading disorientation. The patient with egocentric disorientation demonstrated
      poor performances on both CPT-A and CPT-B. The patient with heading
      disorientation, on the other hand, showed good record results for CPT-A but poor
      ones for CPT-B. An implication is that the patient with egocentric disorientation
      had disorder in an egocentric reference frame per se, while the patient with
      heading disorientation could not integrate information on the spatial locations
      derived from an egocentric reference frame with that on changes of the body
      directions. We suggest that the CPT is a simple and useful clinical test to
      evaluate patients with topographical disorientation.

PMID- 27890880
TI  - Myopericarditis in a case of anti-signal recognition particle (anti-SRP) antibody
      positive myopathy.
AB  - A 79 year-old female was admitted to our hospital because of high serum creatine
      kinase level together with proximal muscle weakness and pain on grasping. MRI
      revealed inflammatory changes in femoral muscles on both sides. Muscle biopsy
      showed size irregularity of muscle cells, and necrosis and regeneration of
      fibers. Study of antibodies was also consistent with the diagnostic criteria of
      anti-signal recognition particle (anti-SRP) antibody-positive myopathy. On
      admission, the patient required pericardiocentesis for the management of
      exudative pericarditis. Accompanying the aggravation of myositis, negative T wave
      in precordial leads on ECG, ventricular extrasystoles and non-sustained
      ventricular tachycardia were observed. These abnormalities were resolved with the
      improvement of myositis by immunosuppressive treatment. These observations
      suggest that the myopericarditis was associated with anti-SRP antibody-positive
      myopathy.

PMID- 27890881
TI  - Non-convulsive status epilepticus with Takotsubo cardiomyopathy: a case report.
AB  - A 61-year-old woman was admitted to our hospital for speech disturbance and mild
      consciousness impairment. Despite the absence of seizures or loss of
      consciousness, electroencephalographic abnormalities were observed, and the
      cerebral blood flow scintigraphy revealed an increase in cerebral blood flow in
      the left temporal lobe. These findings suggested a diagnosis of non-convulsive
      status epilepticus. On the third day, a twelve-lead electrocardiogram showed a
      negative T-wave in I, II, aVf, and V2-6. Moreover, a transthoracic echocardiogram
      revealed left ventricular apical akinesis. However, the coronary angiography
      showed no evidence of vascular stenotic lesions. We expect the present case
      report to contribute to the identification of non-convulsive status epilepticus
      with Takotsubo cardiomyopathy.

PMID- 27890882
TI  - A case of Brugada syndrome which developed status epilepticus.
AB  - A 35-year-old man showed a convulsive attack with consciousness loss and was
      suspected of having Brugada syndrome 6 months prior to admission to our hospital.
      At the initial examination, the patient showed conjugate deviation, followed by
      left limb convulsions and consciousness loss. He regained consciousness after 1
      minute, though cardiac arrest from ventricular fibrillation was noted during an
      electroencephalography (EEG) examination. Sinus rhythm recovered with
      defibrillation, though the convulsions persisted and a Status Epilepticus
      developed. The patient was diagnosed with Brugada syndrome and received
      implantable cardioverter defibrillator (ICD). After ICD, he has suffered no
      further convulsive attacks. Brugada syndrome is an inheritable cardiac disease
      causing sudden death by ventricular fibrillation. It is important to consider
      both epilepsy and arrhythmia in diagnosis of the seizures.

PMID- 27890883
TI  - Questionnaire survey on recruitment for Japanese Neurology Society.
AB  - Many claim that they do not have enough neurologists in Japan, but supply and
      demand of neurologists remains to be analyzed. To investigate the recruitment for
      the Japanese Society of Neurology (JSN), the subcommittee of JSN for education
      performed a questionnaire-based survey in 80 medical universities and 271 board
      certified education facilities throughout Japan. The response rate to the
      questionnaire was 77.5% in medical universities and 42.4% in education
      facilities. It was shown that each department of neurology in university recruits
      average 2.2 doctors, while they supposed that more than 4 doctors to be recruited
      every year. The questionnaire survey included what measures JSN should take in
      order to promote recruitment for JSN.

PMID- 27890884
TI  - Correspondence and challenges as neurologists to Kumamoto Earthquakes in 2016.
AB  - Kumamoto Earthquakes in 2016 severely affected medical circumstances and
      condition of each patient with neuro-muscular diseases, in addition to having
      destroyed life circumstances of local residence. Number of neuro-muscular disease
      patients admitted to the Department of Neurology, Kumamoto University, the only
      university hospital in the prefecture, increased approximately twice compared to
      usual years. Most of the related facilities were able to admit emergency patients
      with neuro-muscular diseases although the hospital buildings were damaged in
      various degrees. A number of issues remained unsolved as to emergency contact
      system, securement of emergency beds for severe neuro-muscular diseases, and
      information system for these patients.

PMID- 27890885
TI  - Medication Adherence Improvement By Using Administration Timing Simplification
      Protocol (ATSP) in Cardiovascular Disease Patients.
AB  - AIMS: In chronic diseases, keeping adherence to medication is very difficult. The
      objective of this study was to evaluate the impact of administration timing
      simplification protocol (ATSP) on medication adherence and clinical parameters of
      cardiovascular diseases. METHODS: 210 out-patients with cardiovascular disease,
      who were taking two or more pills of any type of medication per day for more than
      one year, were enrolled and randomized. The intervention group followed the
      simplified administration schedule of ATSP with two main strategies: 1) moving
      medication from "pc" (30 minute after meal) to "stat. pc" (immediately after
      meal); and 2) moving medication time from "at evening" to "at morning." In
      contrast, the control group maintained the same medication schedule. Both patient
      groups were equally educated about the names and effects of the medication.
      RESULTS: The intervention group had more pills than the control group with
      marginal statistical significance (5.1+/-2.3 vs 4.6+/-1.8, p=0.05). The total
      frequency of administration was significantly higher in the intervention group
      than that of the control group (2.9+/-1.0 vs 2.6+/-0.9, p=0.03) at the baseline.
      In the intervention group, the frequency was significantly decreased to 1.5+/-0.6
      times per day after following ATSP application (p<0.01). In both patient groups,
      knowledge about the medication was significantly improved by education. However,
      medication adherence was only improved in the intervention group. Interestingly,
      total cholesterol was significantly decreased in the intervention group (p<0.01).
      The decrease in serum cholesterol concentration was significantly correlated with
      the improvement in medication adherence evaluated with Morisky Medication
      Adherence Scale (MMAS)-8 items (r=0.507, p<0.01). CONCLUSION: ATSP was shown to
      be an effective strategy to improve medication adherence in chronic
      cardiovascular disease patients.

PMID- 27890886
TI  - Anemia in combined antiretroviral treatment-naive HIV-infected patients in China:
      A retrospective study of prevalence, risk factors, and mortality.
AB  - Anemia is one of the most important complications of HIV infection. In China, the
      prevalence, risk factors, and association between anemia and prognosis in HIV
      infected patients are poorly elucidated. We analyzed data from 3452 HIV-infected
      patients not yet on combined antiretroviral therapy (cART) attending Beijing
      Ditan Hospital from June, 2003 to December, 2015. The overall prevalence of
      anemia was 9.8% (7.6% mild, 1.9% moderate, and 0.2% severe anemia). Female sex
      (odds ratio [OR] = 3.71, 95% confidence interval [CI]: 1.46-6.51, p = 0.003), age
      40-59 years (OR = 2.54, 95% CI: 1.59-4.05, p < 0.001), body mass index < 18.5
      kg/m2 (OR = 2.23, 95% CI: 1.31-3.79, p = 0.003), baseline HIV RNA CI: 1.32-5.99,
      p = 0.007) were risk factors for anemia. Age 40-59 years (adjusted hazard ratio
      [AHR] = 5.76, 95% CI: 1.62-20.55, p = 0.007), and anemia - mild (AHR = 7.46, 95%
      CI: 1.48-37.50, p = 0.015), moderate (AHR = 9.89, CI: 1.35-72.38, p = 0.024), and
      severe (AHR = 28.29, 95% CI: 2.75-290.54, p = 0.005) anemia - were associated
      with an increased hazard of death. In this cohort, mild anemia was most common.
      Anemia was associated with female sex, older age, lower body mass index, lower
      baseline CD4 count, and higher viral load. Moreover, anemia was associated with
      an increased risk of death. These findings should promote awareness among
      physicians to make a timely diagnosis of HIV and to help physicians prioritize
      prevention and intervention strategies for anemia in HIV-infected patients.

PMID- 27890887
TI  - Royal jelly improves hyperglycemia in obese/diabetic KK-Ay mice.
AB  - The study examined whether royal jelly (RJ) can prevent obesity and ameliorate
      hyperglycemia in type 2 diabetes. This study utilized obese/diabetic KK-Ay mice.
      RJ (10 mg/kg) was administered by oral gavage. Body weight, plasma glucose and
      insulin levels were measured. mRNA and protein levels were determined using
      quantitative reverse transcription polymerase chain reaction and western
      blotting, respectively. Four weeks of RJ administration improved hyperglycemia
      and partially suppressed body weight gain, although the latter effect did not
      reach statistical significance. In addition, RJ administration did not improve
      insulin resistance. RJ administration suppressed the mRNA expression of glucose-6
      phosphatase (G6Pase), a key enzyme of gluconeogenesis, in the liver.
      Simultaneously, RJ administration induced adiponectin (AdipoQ) expression in
      abdominal fat, adiponectin receptor-1 (AdipoR1) expression in the liver and
      phosphorylated AMP-activated protein kinase (pAMPK) expression, which suppressed
      G6Pase levels in the livers of KK-Ay mice. pAMPK levels were also increased in
      skeletal muscle, but glucose transporter-4 (Glut4) translocation was not
      increased in the RJ supplementation group. The improvement in hyperglycemia due
      to long-term RJ administration may be because of the suppression of G6Pase
      expression through the upregulation of AdipoQ and AdipoR1 mRNA and pAMPK protein
      expressions.

PMID- 27890890
TI  - Perivascular Hematoma along Pulmonary Artery Complicating Aortic Dissection.

PMID- 27890888
TI  - Cloning and expression of a novel catechol-O-methyltransferase in common
      marmosets.
AB  - Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of endogenous
      catechol amines and estrogens and exogenous catechol-type of drugs. A Parkinson's
      disease model of common marmoset (Callithrix jacchus) has been widely used in
      preclinical studies to evaluate inhibitory potential of new drug candidates on
      marmoset COMT. Despite COMT inhibitors could potentiate the pharmacological
      action of levodopa on Parkinson's disease in animal models, marmoset COMT cDNA
      has not yet been identified and characterized. In this study, a cDNA highly
      homologous to human COMT was cloned from marmoset livers. This cDNA encoded 268
      amino acids containing a transmembrane region and critical amino acid residues
      for catalytic function. The amino acid sequences of marmoset COMT shared high
      sequence identity (90%) with human COMT. COMT mRNA was expressed in all five
      tissues tested, including brain, lung, liver, kidney and small intestine, and was
      more abundant in marmoset liver and kidney. Membrane-bound COMT was
      immunochemically detected in livers and kidneys, whereas soluble COMT was
      detected in livers, similar to humans. These results indicated that the molecular
      characteristics of marmoset COMT were generally similar to the human ortholog.

PMID- 27890889
TI  - First molecular detection of tick-borne pathogens in dogs from Jiangxi, China.
AB  - In this study, blood samples obtained from 162 dogs in Jiangxi, China, were
      employed in molecular screening of canine tick-borne pathogens by PCR and
      sequencing. Babesia spp. gene fragment was detected in 12 (7.41%) dogs. All
      samples were negative for Hepatozoon spp., Ehrlichia canis, Coxiella spp.,
      Borrelia spp., Rickettsia spp. and Anaplasma platys. Species-specific PCR
      analysis further confirmed that 8 (4.94%) and 4 (2.47%) dogs were infected by
      Babesia canis vogeli and Babesia gibsoni, respectively. Based on our analyses,
      Babesia spp. infection in Jiangxi appeared not related to age, gender, breed,
      usage, activity and health status or tick infestation history of the dogs. This
      is the first molecular report of Babesia canis vogeli and Babesia gibsoni in dogs
      from Jiangxi, China.

PMID- 27890891
TI  - Mid-Term Clinical Results of VerSys Hip System (Zimmer) Uncemented Total Hip
      Replacement Arthroplasty.
AB  - : Recent reports suggest that uncemented total hip replacement arthroplasty (THR)
      results in favorable short- to mid-term clinical results. In the present study,
      we assessed the mid-term clinical results of VerSys Hip System uncemented THR at
      our hospital. MATERIALS AND METHODS: We studied patients who received THR using
      VerSys Hip System and who could be followed-up more than 3 years. Clinical
      records were used to retrospectively identify patient characteristics, which
      included age, gender, disease requiring THR, preoperative and postoperative pain
      score of the Japan Orthopaedic Association scoring system, range of motion in
      flexion and abduction, operating time, intraoperative complication, and
      additional operation or revision surgery. Additionally, we investigated the
      loosening and alignment of implants from X-ray films. RESULTS: Ninety-one
      patients and 108 hip joints were investigated. Subjects were 11 males and 97
      females (mean age, 64.6 years). Mean follow-up period was 6.9 years. Reasons for
      requiring THR were as follows: secondary osteoarthritis, 87 joints; idiopathic
      osteonecrosis of the femoral head, 16 joints; rapidly destructive coxarthrosis, 4
      joints; and idiopathic ossification of the labrum, 1 joint. Mean operating time
      was 166 minutes. A total of 11 intraoperative fractures occurred, and wiring was
      performed in 3 of those cases. Adverse events pertaining to the surgery were
      limited; however, another adverse event was that 1 case resulted in
      intraoperative perforation of femoral cortex, for which a revision surgery was
      performed. There was no dislocation. Pain score using the Japan Orthopaedic
      Association scoring system and range of motion tests showed statistically
      significant improvement following THR. At the final follow-up, although no
      loosening of femoral implants was observed, the loosening of acetabular component
      was seen in 1 case. Varus insertion of femoral implant was recognized in 40
      joints. Moreover, the average inclination angle of acetabular implants was 52.2
      degrees. CONCLUSION: These data suggest that patients receiving VerSys Hip System
      uncemented THR demonstrate favorable results pertaining pain score and range of
      motion. However, high rate of intraoperative fracture and malalignment of
      implants, which may be at a risk of dislocation and/or polyethylene wear in
      future, suggests that this implant technique requires improvement.

PMID- 27890892
TI  - A Survey of Actual Clinical Practice Concerning Blood Pressure Control among
      Patients with Hypertension in Kanagawa 2014.
AB  - We performed a cross-sectional survey to investigate actual clinical practice
      concerning blood-pressure control among patients with hypertension in Kanagawa.
      The guidelines of the Japanese Society of Hypertension (JSH) for the management
      of patients with hypertension were revised in 2014. From October 1 to November
      30, 2014, questionnaires on the care of patients with hypertension were sent via
      post to members of the Kanagawa Physicians Association in Kanagawa Prefecture,
      Japan. -Data on 1,105 patients (mean age: 68.4+/-12.3 years, 537 men and 568
      women) were obtained. The overall mean systolic blood pressure (BP) of these
      patients was 128.7+/-12.1 mmHg for home monitoring and 132.9+/-12.6 mmHg for
      office monitoring; diastolic BP was 75.7+/-9.7 for home monitoring and 77.0+/-9.7
      mmHg for office monitoring. According to the JSH 2014 guidelines, the target BP
      was achieved by 68.1% of all subjects; 89.2% of late-phase elderly patients (75
      years or older); 69.1% of young, middle-aged, and early-phase elderly patients
      (younger than 75 years except in patients with diabetes mellitus [DM] or chronic
      kidney disease [CKD] with proteinuria); 9.3% of patients with DM except late
      phase elderly patients; and 11.9% of CKD patients with proteinuria except DM.
      Cross-sectional analysis showed that the factors significantly associated with an
      increased likelihood of achieving the target BP were as follows: 1) good
      medication compliance even for a small number of antihypertensive agents at small
      amount of doses in patients 75 years and older; 2) good medication compliance in
      patients in younger than 75 years; 3) an older age, a larger proportion in the
      female-to-male ratio and a lower body mass index in patients with DM except late
      phase elderly patients; and 4) usage of a large number of antihypertensive agents
      in CKD patients with proteinuria. Further follow-up surveys are necessary to
      investigate changes in clinical practice following the introduction of the
      revised guidelines.

PMID- 27890893
TI  - Successful Coil Embolization of an Aneurysm in the Arc of Buhler.
AB  - In the present report, we describe a case of a patient with an asymptomatic
      aneurysm in the arc of Buhler (AOB), which was successfully treated by
      transcatheter arterial embolization. The patient presented with severe stenosis
      of the celiac trunk, which was suspected to be due to median arcuate ligament
      syndrome. Arteriography of the superior mesenteric artery indicated a rapid
      stream in an aneurysm in the AOB. Hence, embolization was carefully performed
      using detachable coils and microcoils. An arteriography performed after
      embolization did not show any aneurysm, and the hepatic artery and splenic artery
      could be detected via the pancreatic arcade, originating from the superior
      mesenteric artery. The AOB is a persistent embryonic ventral anastomosis present
      between the superior mesenteric artery and the celiac artery. This anastomotic
      artery is independent of the gastroduodenal artery and the dorsal pancreatic
      artery, and is extremely rare, with an incidence of <4%. Aneurysms of the AOB are
      even more uncommon, and such cases have been reported in association with
      stenosis or occlusion of the celiac trunk. Open surgical aneurysmectomy, with or
      without reconstruction, is the conventional treatment for such aneurysms.
      However, rapid advances in interventional radiology have enabled the safe and
      effective treatment of visceral aneurysms via transcatheter arterial
      embolization. Based on the current findings, we believe that transcatheter
      arterial embolization is a minimally invasive and valuable method that may serve
      as an initial treatment option for aneurysms of the AOB.

PMID- 27890894
TI  - Clinical Complete Response from Chemotherapy in an Elderly Patient with
      Metastatic Gastric Cancer: A Case Report.
AB  - An 81-year-old man was admitted with upper abdominal pain and weight loss.
      Esophagogastroduodenoscopy revealed a large tumor located from the gastric angle
      to the body. Histological analysis of a biopsy revealed a moderately
      differentiated adenocarcinoma. Computed tomography revealed metastases in the
      liver and lung and the patient was subsequently diagnosed with metastatic
      advanced gastric cancer. He was treated with chemotherapy using S-1 (80 mg/m2)
      and cisplatin (CDDP) (60 mg/m2). Twenty-two months after chemotherapy, the
      gastric tumor, and the nodules in the liver and lung, had disappeared. We
      subsequently diagnosed a clinical complete response. The patient was treated with
      further S-1 monotherapy for 7 months after complete response assessment. He has
      lived for more than 7 years since the initial diagnosis without recurrence.
      Chemotherapy using S-1 and CDDP may be a potent strategy for improving survival
      in elderly patients with advanced gastric cancer.

PMID- 27890895
TI  - Efficacy of Computed Tomography-Guided Catheter Drainage as the Initial
      Intervention and of Omentopexy as the Staged Surgery for a Prosthetic Graft
      Infection of Very Late Onset.
AB  - On the basis of computed tomography (CT) examination, a prosthetic graft
      infection of very late onset was suspected in a 72-year-old man who had undergone
      replacement of an bifurcated prosthetic graft 6 years earlier because of an
      abdominal aortic aneurysm and bilateral common iliac artery aneurysms. Emergency
      CT-guided needle aspiration was performed, and analysis of directly aspirated
      fluid confirmed the rapid diagnosis. Instead of conventional emergency surgery,
      CT-guided catheter drainage was the initial treatment and led to the gradual
      improvement of symptoms and laboratory data. Elective staged surgery was
      performed later to examine the cavity around the prosthetic graft. The cavity was
      then filled with in-situ omentum. Thus, CT-guided catheter drainage as the
      initial treatment and following omentopexy as the staged surgery avoided the need
      for highly invasive conventional surgery.

PMID- 27890896
TI  - Interventional Treatment of Severe Portal Vein Thrombosis after Living-Donor
      Liver Transplantation.
AB  - Portal vein thrombosis (PVT) is a rare complication of liver transplantation
      which can lead to graft failure and patient death. Treatment can be difficult,
      especially in cases of PVT from the intrahepatic portal vein to the proximal
      jejunal veins. A 55-year-old woman had undergone living-donor liver
      transplantation with splenectomy for end-stage liver cirrhosis due to hepatitis C
      with hepatocellular carcinoma. Ten months after transplantation, massive ascites
      and slight abdominal pain developed, and computed tomography revealed a PVT
      between the intrahepatic portal vein and the superior mesenteric vein. Repeated
      interventional radiology procedures were used in combination with thrombolysis,
      thrombectomy, and metallic stent replacement to obtain favorable portal flow to
      the graft. Five years after being treated, the patient is well, with favorable
      portal flow having been confirmed. In conclusion, repeated and assiduous
      interventional radiological treatment combined with thrombolytic therapy,
      thrombectomy, and metallic stent replacement could be important for severe PVT.

PMID- 27890897
TI  - Pott's Puffy Tumor in an Adult: A Case Report and Review of Literature.
AB  - Pott's puffy tumor is a subperiosteal abscess of the frontal bone with
      osteomyelitis which has become rare because of the widespread use of antibiotics.
      Here, we report a case of Pott's puffy tumor in a 46-year-old man who visited the
      department of dermatology with painful swelling of the forehead. Despite open
      drainage and oral antibiotic therapy, the symptoms recurred twice in the
      following month. Computed tomography revealed a fistula of frontal bone. The
      eventual diagnosis was Pott's puffy tumor. The patient underwent endoscopic
      surgery at the department of otorhinolaryngology and achieved a complete
      recovery.

PMID- 27890898
TI  - Therapeutic oligonucleotides and delivery technologies: Research topics in Japan.
AB  - Oligonucleotides have been gaining considerable attention as promising and
      effective candidate therapeutics against various diseases. This special issue is
      aimed at providing a better understanding of the recent progress in the
      development of oligonucleotide-based therapeutics to encourage further research
      and innovation in this field to achieve these advancements. Several Japanese
      scientists have been invited to contribute to this issue by describing their
      recent findings, overviews, insights, or commentaries on rational designing of
      therapeutic oligonucleotide molecules and their novel delivery technologies,
      especially nanocarrier systems.

PMID- 27890899
TI  - Drug delivery system of therapeutic oligonucleotides.
AB  - Therapeutic oligonucleotides are promising technologies. Nevertheless,
      improvement of their efficacy is an important issue. Introducing this drug
      delivery system (DDS) makes for a great enhancement for delivery of
      oligonucleotides to targeted tissue or cells. The strategy of DDS for therapeutic
      oligonucleotides is divided into four categories, A) single piece of
      oligonucleotide, B) oligonucleotide-ligand conjugate, C) oligonucleotide-polymer
      conjugate, and D) nanoparticle. In this review we will describe those basic
      concepts, especially for the technology of conjugating ligand. In addition, we
      developed a new technology, heteroduplex oligonucleotide (HDO), binding ligand
      molecule to antisense oligonucleotide indirectly. We also outline alpha
      tocopherol (a natural isomer of vitamin E) conjugated HDO.

PMID- 27890900
TI  - In vitro and in vivo biophysical properties of oligonucleotides containing 5'
      thio nucleosides.
AB  - Phosphorothioate modification is one of the most widely investigated and
      promising chemical modifications in oligonucleotide (ON) based therapeutics.
      Structurally similar 5'-thio or phosphorothiolate-modified nucleotides, in which
      a 5'-bridging oxygen is replaced with a sulfur atom, are gaining importance for
      ON-based research. Several reports have been published describing the synthesis
      of 5'-thio-modified ONs but no detailed in vitro and in vivo data are available.
      Here, we report the synthesis of 5'-thio-modified 2'-deoxy-5-methylcytidine. 5'
      Thio-modified thymidine and 2'-deoxy-5-methylcytidine were incorporated into
      target ONs, then we evaluated their binding affinity, nuclease stability, RNase H
      mediated scission, stability in blood serum, and in vitro and in vivo activity.
      This is the first report showing the influence of 5'-thio-modified antisense ONs
      in in vitro and in vivo experiments.

PMID- 27890901
TI  - Can colorectal delivery technology provide a platform for enteral oligonucleotide
      based therapeutics?
AB  - Nucleic acid-based therapeutics including antisense and siRNA oligonucleotides
      has been expected as an innovative treatment for intractable diseases. Oral drug
      delivery is the most patient-friendly route of administration but developing an
      effective delivery system for oligonucleotides remains a major challenge. In this
      commentary, we discuss the potential benefits of the colorectal route as another
      platform for the development of oral oligonucleotide therapeutics. The importance
      of the targeting or the availability of oligonucleotides in targeted tissue is
      highlighted in contrast to systemic availability, while the liver-targeted
      enteral siRNA delivery technology that we recently developed is introduced.

PMID- 27890904
TI  - Pharmacokinetic studies of the recombinant chicken interferon-alpha in broiler
      chickens.
AB  - In this study, 24 male and female broiler chickens at 30-day-old were divided
      into three groups with 8 animals in each group. The animals were administered
      with recombinant chicken interferon-alpha (rChIFN-alpha) at a dose of 1.0 * 106
      IU/kg intravenously, intramuscularly or subcutaneously, respectively. Serum
      samples were collected at different time points post administration, and the
      titers of rChIFN-alpha in the blood were determined by cytopathic effect
      inhibition assay. The results showed that the pharmacokinetic characteristics of
      rChIFN-alpha by intramuscular injection and subcutaneous injection were fitted to
      one compartment open model, and the Tmax was 3.21 +/- 0.79 hr and 3.95 +/- 0.85
      hr, respectively, and the elimination half-life (T1/2) was 6.20 +/- 2.77 hr and
      5.03 +/- 3.70 hr, respectively. In contrast, the pharmacokinetics of rChIFN-alpha
      via intravenous injection was in line with the open model of two-compartment and
      was eliminated in the first order, and the elimination half-life (T1/2) was 4.61
      +/- 0.84 hr. In addition, compared with those in the intravenous group and the
      subcutaneous group, the bioavailability of rChIFN-alpha in the intramuscular
      group was 82.80%. In conclusion, rChIFN-alpha was rapidly absorbed and slowly
      eliminated after intramuscular administration of single dose of rChIFN-alpha
      aqueous formulations. Thus, rChIFN-alpha can be used as a commonly-used
      therapeutic agent.

PMID- 27890905
TI  - Bone morphogenetic protein 1 is expressed in porcine ovarian follicles and
      promotes oocyte maturation and early embryonic development.
AB  - In the present study, we tried to determine whether bone morphogenetic protein 1
      (BMP1) plays a role in ovarian follicular development and early embryo
      development. We systematically investigated the expression and influence of BMP1
      during porcine follicle and early embryonic development. Immunohistochemistry
      demonstrated that the BMP1 protein is expressed in granular cells and oocytes
      during follicular development, from primary to pre-ovulatory follicles, including
      atretic follicles and the corpus luteum. The mRNA expression of BMP1
      significantly increased as the porcine follicles grew. Immunofluorescence
      analysis indicated that BMP1 was expressed in cumulus-oocyte complexes (COCs),
      oocytes and porcine embryos during early in vitro culture. qPCR and western blot
      analysis showed that the expression of BMP1 was significantly up-regulated in
      mature porcine oocytes and COCs compared to immature oocytes and COCs. BMP1 is
      expressed in early porcine embryos, and its expression reaches a peak at the 8
      cell stage. To determine the effect of BMP1 on the maturation of oocytes and the
      development of early embryos, various concentrations of BMP1 recombinant protein
      or antibody were added to the in vitro culture media, respectively. BMP1
      significantly affected the porcine oocyte maturation rate, the cleavage rate and
      the blastocyst development rate of embryos cultured in vitro in a positive way,
      as well as the blastocyst cell number. In conclusion, BMP1 is expressed
      throughout porcine ovarian follicle development and early embryogenesis, and it
      promotes oocyte maturation and the developmental ability of embryos during early
      in vitro culture.

PMID- 27890907
TI  - Relationship between serum gonadotropin concentrations and thyroid volume in
      women with polycystic ovary syndrome.

PMID- 27890906
TI  - Accuracy of the evaluation method for alkaline agents' bactericidal efficacies in
      solid, and the required time of bacterial inactivation.
AB  - An alkaline agent, namely food additive grade calcium hydroxide (FdCa (OH)2) in
      the powder form, was evaluated for its bactericidal efficacies in chicken feces
      at pH 13. The point for this evaluation was neutralization of the alkaline
      agent's pH at the time of bacterial recovery, since otherwise the results are
      substantially misleading. Without neutralization of the FdCa (OH)2 pH, the spiked
      bacteria were killed within min at the time of recovery in aqueous phase, but not
      in the solid form in feces, hence, it has been demonstrated that when bacteria
      were in solid, it took longer time than in liquid for the alkaline agent to
      inactivate them down to the acceptable level (>=3 log10 CFU/ml).

PMID- 27890908
TI  - Electronic cigarettes: a new challenge for Polish public health.

PMID- 27890909
TI  - Symptoms mimicking Sjogren syndrome in a heterozygous carrier of CFTR deltaF508
      mutation.

PMID- 27890910
TI  - Left circumflex coronary artery aneurysm with arteriovenous fistula to the
      coronary sinus presenting as acute coronary syndrome.

PMID- 27890911
TI  - Suprapedicular Foraminal Endoscopic Approach to Lumbar Lateral Recess
      Decompression Surgery to Treat Degenerative Lumbar Spinal Stenosis.
AB  - BACKGROUND To discuss the strategy of suprapedicular foraminal endoscopic
      approach to lumbar lateral recess decompression and evaluate the safety and
      effectiveness of this strategy. MATERIAL AND METHODS Complete clinical
      information of 52 cases of lumbar lateral recess decompression with therapy of
      suprapedicular foraminal endoscopic approach were analyzed during the period from
      February 2010 to April 2014 in the Third Hospital of Hebei. All patients were
      followed up for 24 months, and VAS, JOA, ODI, and LRD were compared between
      preoperative and postoperative therapy and changes of FA. Intraoperative and
      postoperative complications were recorded and the safety of the surgery was
      evaluated. The surgical "excellent" and "good" rates were evaluated using MacNab
      score. RESULTS VAS scores for lumbago and leg pain at 3, 6, 12, and 24 months
      after surgery were significantly lower than before surgery (p<0.05). JOA scores
      at 12 and 24 months after surgery were significantly higher than before surgery
      (p<0.05). ODI at 12 and 24 months after surgery were significantly lower than
      before surgery (p<0.05). LRD after surgery was higher (p<0.05), and FA was lower
      than before surgery. CONCLUSIONS Use of the suprapedicular foraminal endoscopic
      approach to lumbar lateral recess decompression is safe and effective, and this
      minimally invasive treatment can achieve satisfactory results, especially for
      elderly patients with complicated underlying diseases.

PMID- 27890912
TI  - Performance of Laparoscopic Pancreatoduodenectomy for Solid Pseudopapillary Tumor
      of Pancreas.
AB  - BACKGROUND Solid pseudopapillary tumor of the pancreas (Frantz tumor) is a rare,
      low-grade malignant neoplasm. Laparoscopic pancreatoduodenectomy is a good
      approach for tumors located in the pancreatic head. We present two successful
      cases in young women. CASE REPORT A 19-year-old woman was admitted to Department
      of Digestive Surgery due to epigastric pain, nausea, and vomiting. Computed
      tomography scan of the abdomen was performed, and a 3.0*2.2 cm solid tumor
      localized in the head of the pancreas was observed. After the diagnosis of Frantz
      tumor of the pancreas, the patient underwent laparoscopic pancreatoduodenectomy.
      Histopathology confirmed solid and cystic pseudopapillary tumor. The
      postoperative course was uneventful, and after 8 months the patient remained
      disease-free. An 18-year-old woman was admitted at the emergency room with
      abdominal pain, vomiting, and diarrhea. Computed tomography scans revealed a mass
      of 4.1*3.3 cm in size in the head of the pancreas consistent with a solid
      pseudopapillary tumor. Laparoscopic pancreatoduodenectomy was performed by two
      expert surgeons who divided the work: one did resection and the other did
      reconstruction. The patient was discharged at postoperative day 6 without
      complications, and during five months of follow-up the patient has been well and
      without disease. CONCLUSIONS Laparoscopic pancreatoduodenectomy can be performed
      safely in patients with Frantz tumor by surgeons with expertise in laparoscopic
      surgery, technical skill, and adequate equipment.

PMID- 27890913
TI  - Early local immune defences in the respiratory tract.
AB  - The respiratory immune response consists of multiple tiers of cellular responses
      that are engaged in a sequential manner in order to control infections. The
      stepwise engagement of effector functions with progressively increasing host
      fitness costs limits tissue damage. In addition, specific mechanisms are in place
      to promote disease tolerance in response to respiratory infections. Environmental
      factors, obesity and the ageing process can alter the efficiency and regulation
      of this tiered response, increasing pathology and mortality as a result. In this
      Review, we describe the cell types that coordinate pathogen clearance and tissue
      repair through the serial secretion of cytokines, and discuss how the environment
      and comorbidity influence this response.

PMID- 27890915
TI  - Pharmacological evidence: a new therapeutic approach to the treatment of chronic
      heart failure through SUR2B/Kir6.1 channel in endothelial cells.
AB  - Both iptakalim (Ipt) and natakalim (Nat) activate the SUR2B/Kir6.1 channel, an
      ATP-sensitive potassium channel (KATP) subtype, with high selectivity. In this
      study we investigated the therapeutic effects of Ipt and Nat against
      isoproterenol-induced chronic heart failure (ISO-CHF) in rats, and demonstrated a
      new therapeutic approach to the treatment of CHF through activation of the
      SUR2B/Kir6.1 channel in endothelial cells. In ISO-CHF rats, oral administration
      of Nat (1, 3, 9 mg.kg-1.d-1) or Ipt (3 mg.kg-1.d-1) for 60 days significantly
      improved cardiac dysfunction, reversed cardiac remodeling, significantly
      attenuated the pathological increases in BNP levels, and improved endothelial
      dysfunction by adjusting the balance between endothelin and NO systems. The
      therapeutic effects of Nat were prevented by the selective KATP blocker
      glibenclamine (Gli, 50 mg.kg-1.d-1), confirming that these effects were mediated
      through activation of the SUR2B/Kir6.1 channel in endothelial cells. The
      molecular mechanisms underlying the therapeutic effects of Nat were further
      addressed using proteomic methods. We identified 724 proteins in the plasma of
      ISO-CHF rats; 55 proteins were related to Nat. These differentially expressed
      proteins were mainly involved in single-organism processes and the regulation of
      biological quality relative to CHF, including proteasome (Psm) and ATP protein
      clusters. We screened out PRKAR2beta, GAS6/eNOS/NO and NO/PKG/VASP pathways
      involved in the amelioration of CHF among the 24 enriched pathways. We further
      confirmed 6 protein candidates, including PRKAR2beta, GAS6 and VASP, which were
      involved in the endothelial mechanisms, and ATP, TIMP3 and AGT, which contributed
      to its cardiovascular actions. This study demonstrates a new pharmacological
      approach to the treatment of CHF through activation of the SUR2B/Kir6.1 channel
      in endothelial cells, and that the eNOS/VASP pathways are involved in its
      signaling mechanisms.

PMID- 27890914
TI  - Dendritic cell migration in health and disease.
AB  - Dendritic cells (DCs) are potent and versatile antigen-presenting cells, and
      their ability to migrate is key for the initiation of protective pro-inflammatory
      as well as tolerogenic immune responses. Recent comprehensive studies have
      highlighted the importance of DC migration in the maintenance of immune
      surveillance and tissue homeostasis, and also in the pathogenesis of a range of
      diseases. In this Review, we summarize the anatomical, cellular and molecular
      factors that regulate the migration of different DC subsets in health and
      disease. In particular, we focus on new insights concerning the role of migratory
      DCs in the pathogenesis of diseases of the skin, intestine, lung, and brain, as
      well as in autoimmunity and atherosclerosis.

PMID- 27890916
TI  - Polydatin ameliorates Staphylococcus aureus-induced mastitis in mice via
      inhibiting TLR2-mediated activation of the p38 MAPK/NF-kappaB pathway.
AB  - Recent studies show that Polydatin (PD) extracted from the roots of Polygonum
      cuspidatum Sieb, a widely used traditional Chinese remedies, possesses anti
      inflammatory activity in several experimental models. In this study, we
      investigated the anti-inflammatory effects of PD on Staphylococcus aureus-induced
      mastitis in mice and elucidated the potential mechanisms. In mice with S aureus
      induced mastitis, administration of PD (15, 30, 45 mg/kg, ip) or dexamethasone
      (Dex, 5 mg/kg, ip) significantly suppressed the infiltration of inflammatory
      cells, ameliorated the mammary structural damage, and inhibited the activity of
      myeloperoxidase, a biomarker of neutrophils accumulation. Furthermore, PD
      treatment dose-dependently decreased the levels of TNF-alpha, IL-1beta, IL-6 and
      IL-8 in the mammary gland tissues. PD treatment also dose-dependently decreased
      the expression of TLR2, MyD88, IRAK1, IRAK4 and TRAF6 as well as the
      phosphorylation of TAK1, MKK3/6, p38 MAPK, IkappaB-alpha and NF-kappaB in the
      mammary gland tissues. In mouse mammary epithelial cells (mMECs) infected by S
      aureus in vitro, pretreatment with PD dose-dependently suppressed the upregulated
      pro-inflammatory cytokines and signaling proteins, and the nuclear translocation
      of NF-kappaB p65 and AP-1. A TLR2-neutralizing antibody mimicked PD in its
      suppression on S aureus-induced upregulation of MyD88, p-p38 and p-p65 levels in
      mMECs. PD (50, 100 MUg/mL) affected neither the growth of S aureus in vitro, nor
      the viability of mMECs. In conclusion, PD does not exhibit antibacterial activity
      against S aureus, its therapeutic effects in mouse S aureus-induced mastitis
      depend on its ability to down-regulate pro-inflammatory cytokine levels via
      inhibiting TLR2-mediated activation of the p38 MAPK/NF-kappaB signaling pathway.

PMID- 27890917
TI  - Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616
      5p-mediated GSK3beta/beta-catenin signaling pathways.
AB  - Sulforaphane is a common antioxidant selectively abundant in cruciferous plants,
      which exhibits effective anti-cancer actions in control of tumorigenesis or
      progression of various cancers. A recent study has shown that sulforaphane
      attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC),
      suggesting its potential anti-metastatic effects. In this study we assessed the
      involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition
      (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in
      human NSCLC cell lines H1299, 95C and 95D with IC50 values of 9.52+/-1.23, 9.04+/
      1.90 and 17.35+/-2.03 MUmol/L, respectively. At low concentrations (1-5 MUmol/L),
      sulforaphane dose-dependently inhibited the migration and invasion of 95D and
      H1299 cells with relatively high metastatic potential. The anti-metastatic action
      of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh
      NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in
      late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and
      metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3
      NSCLC cell lines were correlated with their metastatic ability, and were
      decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the
      migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo.
      Further studies revealed that miR-616-5p directly targeted GSK3beta and decreased
      its expression, whereas sulforaphane decreased miR-616-5p levels by histone
      modification, and followed by inactivation of the GSK3beta/beta-catenin signaling
      pathway and inhibition of EMT, which was characterized by loss of epithelial
      markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings
      suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the
      prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically
      utilized as a biomarker or therapeutic target to inhibit metastasis.

PMID- 27890918
TI  - 2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction
      in mice via modulation of the FcepsilonRI signaling pathway.
AB  - Mast cells are important effector cells in immunoglobulin (Ig) E-mediated
      allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid,
      a natural product, has shown anti-oxidant and anti-inflammatory activities. In
      the present study, we investigated the anti-allergic inflammatory effects of
      ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative
      of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models,
      oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated
      ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic
      reactions such as hypothermia, histamine release, IgE production and
      vasodilation; administration of o-VA also suppressed the mast cell degranulator
      compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and
      isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100
      MUmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells
      by decreasing the intracellular free calcium level, and suppressed the expression
      of pro-inflammatory cytokines TNF-alpha and IL-4. Pretreatment of RBL-2H3 cells
      with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the
      nuclear translocation of nuclear factor-kappaB. In conclusion, o-VA suppresses
      the mast cell-mediated allergic inflammatory response by blocking the signaling
      pathways downstream of high affinity IgE receptor (FcepsilonRI) on the surface of
      mast cells.

PMID- 27890921
TI  - Bacterial Physiology: Quorum sensing controls the cost of CRISPR-Cas.

PMID- 27890919
TI  - Human gammadeltaT-cell subsets and their involvement in tumor immunity.
AB  - gammadeltaT cells are a conserved population of innate lymphocytes with diverse
      structural and functional heterogeneity that participate in various immune
      responses during tumor progression. gammadeltaT cells perform potent
      immunosurveillance by exerting direct cytotoxicity, strong cytokine production
      and indirect antitumor immune responses. However, certain gammadeltaT-cell
      subsets also contribute to tumor progression by facilitating cancer-related
      inflammation and immunosuppression. Here, we review recent observations regarding
      the antitumor and protumor roles of major structural and functional subsets of
      human gammadeltaT cells, describing how these subsets are activated and
      polarized, and how these events relate to subsequent function in tumor immunity.
      These studies provide insights into the manipulation of gammadeltaT-cell function
      to facilitate more targeted approaches for tumor therapy.Cellular & Molecular
      Immunology advance online publication, 28 November 2016; doi:10.1038/cmi.2016.55.

PMID- 27890920
TI  - Protein export through the bacterial Sec pathway.
AB  - The general secretory (Sec) pathway comprises an essential, ubiquitous and
      universal export machinery for most proteins that integrate into, or translocate
      through, the plasma membrane. Sec exportome polypeptides are synthesized as pre
      proteins that have cleavable signal peptides fused to the exported mature
      domains. Recent advances have re-evaluated the interaction networks of pre
      proteins with chaperones that are involved in pre-protein targeting from the
      ribosome to the SecYEG channel and have identified conformational signals as
      checkpoints for high-fidelity targeting and translocation. The recent structural
      and mechanistic insights into the channel and its ATPase motor SecA are important
      steps towards the elucidation of the allosteric crosstalk that mediates
      secretion. In this Review, we discuss recent biochemical, structural and
      mechanistic insights into the consecutive steps of the Sec pathway - sorting and
      targeting, translocation and release - in both co-translational and post
      translational modes of export. The architecture and conformational dynamics of
      the SecYEG channel and its regulation by ribosomes, SecA and pre-proteins are
      highlighted. Moreover, we present conceptual models of the mechanisms and
      energetics of the Sec-pathway dependent secretion process in bacteria.

PMID- 27890925
TI  - DNA elements: The ins and outs of enhancer validation.

PMID- 27890926
TI  - Cancer genomics: Single-cell RNA-seq to decipher tumour architecture.

PMID- 27890922
TI  - Progress in imaging methods: insights gained into Plasmodium biology.
AB  - Over the past decade, major advances in imaging techniques have enhanced our
      understanding of Plasmodium spp. parasites and their interplay with mammalian
      hosts and mosquito vectors. Cryoelectron tomography, cryo-X-ray tomography and
      super-resolution microscopy have shifted paradigms of sporozoite and gametocyte
      structure, the process of erythrocyte invasion by merozoites, and the
      architecture of Maurer's clefts. Intravital time-lapse imaging has been
      revolutionary for our understanding of pre-erythrocytic stages of rodent
      Plasmodium parasites. Furthermore, high-speed imaging has revealed the link
      between sporozoite structure and motility, and improvements in time-lapse
      microscopy have enabled imaging of the entire Plasmodium falciparum erythrocytic
      cycle and the complete Plasmodium berghei pre-erythrocytic stages for the first
      time. In this Review, we discuss the contribution of key imaging tools to these
      and other discoveries in the malaria field over the past 10 years.

PMID- 27890924
TI  - Cellular plasticity in kidney injury and repair.
AB  - Terminally differentiated cells can be reprogrammed to pluripotency or directly
      to another differentiated cell type in vitro, a capacity termed cellular
      plasticity. Plasticity is not limited to in vitro manipulations but rather
      represents an important aspect of the regenerative response to injury in organs.
      Differentiated adult cells retain the capacity to dedifferentiate, adopting a
      progenitor-like phenotype after injury or, alternatively, to transdifferentiate,
      directly converting to a different mature cell type. Emerging concepts on
      cellular plasticity have relevance to our understanding of repair after kidney
      injury, including epithelial regeneration. Here we discuss work published in the
      past 5 years on the cellular hierarchies and mechanisms underlying kidney injury
      and repair, with a particular focus on potential roles for cellular plasticity in
      this response.

PMID- 27890928
TI  - Identification and characterization of activating ABL1 1b kinase mutations:
      impact on sensitivity to ATP-competitive and allosteric ABL1 inhibitors.
AB  - Although pathologically activated ABL1 fusion kinases represent well-validated
      therapeutic targets, tumor genomic sequencing has identified numerous point
      mutations in the ABL1 proto-oncogene of unclear significance. Here we describe
      ten novel ABL1 1b point mutations, including two from clinical isolates, that
      cause constitutive kinase activation and cellular transformation. All mutants
      retained sensitivity to ATP-competitive tyrosine kinase inhibitors (TKIs).
      Several substitutions cluster near the myristoyl-binding pocket, the target of
      ABL001, a novel clinically active allosteric kinase inhibitor that mimics the
      autoinhibitory myristoyl group, and likely activate the kinase by relieving
      physiologic autoinhibition. In addition, several mutations activate the kinase
      and confer resistance to allosteric inhibition despite a lack of proximity to
      this region. We demonstrate that BCR-ABL1 and ABL1 1b point mutations can co
      exist in a proportion of clinical cases as a consequence of the chromosome 9
      breakpoint location. Collectively, our findings support clinical investigation of
      ATP-competitive TKIs in malignancies harboring ABL1 point mutations, and
      sequencing of BCR-ABL1 and ABL1 1b in patients with acquired resistance to
      allosteric ABL1 inhibitors.

PMID- 27890923
TI  - The epigenetic landscape of renal cancer.
AB  - The majority of kidney cancers are associated with mutations in the von Hippel
      Lindau gene and a small proportion are associated with infrequent mutations in
      other well characterized tumour-suppressor genes. In the past 15 years, efforts
      to uncover other key genes involved in renal cancer have identified many genes
      that are dysregulated or silenced via epigenetic mechanisms, mainly through
      methylation of promoter CpG islands or dysregulation of specific microRNAs. In
      addition, the advent of next-generation sequencing has led to the identification
      of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and
      SETD2, which are all involved in histone modification and nucleosome and
      chromatin remodelling. In this Review, we discuss how altered DNA methylation,
      microRNA dysregulation and mutations in histone-modifying enzymes disrupt
      cellular pathways in renal cancers.

PMID- 27890927
TI  - The AP-1 transcription factor JunB is essential for multiple myeloma cell
      proliferation and drug resistance in the bone marrow microenvironment.
AB  - Despite therapeutic advances, multiple myeloma (MM) remains an incurable disease,
      predominantly because of the development of drug resistance. The activator
      protein-1 (AP-1) transcription factor family has been implicated in a multitude
      of physiologic processes and tumorigenesis; however, its role in MM is largely
      unknown. Here we demonstrate specific and rapid induction of the AP-1 family
      member JunB in MM cells when co-cultured with bone marrow stromal cells.
      Supporting a functional key role of JunB in MM pathogenesis, knockdown of JUNB
      significantly inhibited in vitro MM cell proliferation and survival.
      Consistently, induced silencing of JUNB markedly decreased tumor growth in a
      murine MM model of the microenvironment. Subsequent gene expression profiling
      revealed a role for genes associated with apoptosis, DNA replication and
      metabolism in driving the JunB-mediated phenotype in MM cells. Importantly,
      knockdown of JUNB restored the response to dexamethasone in dexamethasone
      resistant MM cells. Moreover, 4-hydroxytamoxifen-induced activation of a JunB-ER
      fusion protein protected dexamethasone-sensitive MM cells against dexamethasone-
      and bortezomib-induced cytotoxicity. In summary, our results demonstrate for the
      first time a specific role for AP-1/JunB in MM cell proliferation, survival and
      drug resistance, thereby strongly supporting that this transcription factor is a
      promising new therapeutic target in MM.

PMID- 27890929
TI  - Extended time-lapse in vivo imaging of tibia bone marrow to visualize dynamic
      hematopoietic stem cell engraftment.
AB  - Homing, engraftment and proliferation of hematopoietic stem/progenitor cell
      (HSC/HPCs) are crucial steps required for success of a bone marrow transplant.
      Observation of these critical events is limited by the opaque nature of bone.
      Here we demonstrate how individual HSCs engraft in long bones by thinning one
      side of the tibia for direct and unbiased observation. Intravital imaging enabled
      detailed visualization of single Sca-1+, c-Kit+, Lineage- (SKL) cell migration to
      bone marrow niches and subsequent proliferation to reconstitute hematopoiesis.
      This longitudinal study allowed direct observation of dynamic HSC/HPC activities
      during engraftment in full color for up to 6 days in live recipients. Individual
      SKL cells, but not mature or committed progenitor cells, preferentially homed to
      a limited number of niches near highly vascularized endosteal regions, and
      clonally expanded. Engraftment of SKL cells in P-selectin and osteopontin
      knockout mice showed abnormal homing and expansion of SKL cells. CD150+, CD48-
      SKL populations initially engrafted in the central marrow region, utilizing only
      a subset of niches occupied by the parent SKL cells. Our study demonstrates that
      time-lapse imaging of tibia can be a valuable tool to understand the dynamic
      characteristics of functional HSC and niche components in various mouse models.

PMID- 27890930
TI  - Histone deacetylase inhibitors interrupt HSP90*RASGRP1 and HSP90*CRAF
      interactions to upregulate BIM and circumvent drug resistance in lymphoma cells.
AB  - Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of
      cutaneous T-cell lymphoma and multiple myeloma, are undergoing evaluation in
      other lymphoid neoplasms. How they kill susceptible cells is incompletely
      understood. Here, we show that trichostatin A, romidepsin and panobinostat induce
      apoptosis across a panel of malignant B cell lines, including lines that are
      intrinsically resistant to bortezomib, etoposide, cytarabine and BH3 mimetics.
      Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased
      acetylation of the chaperone heat shock protein 90 (HSP90), causing release and
      degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to
      downregulation of mitogen-activated protein kinase pathway signaling and
      upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo.
      Importantly, these pro-apoptotic effects are mimicked by RASGRP1 small
      interfering RNA (siRNA) or HSP90 inhibition and reversed by overexpression of
      constitutively active MEK1 or siRNA-mediated downregulation of BIM. Collectively,
      these observations not only identify a new HSP90 client protein, RASGRP1, but
      also delineate a complete signaling pathway from HSP90 acetylation through
      RASGRP1 and CRAF degradation to BIM upregulation that contributes to selective
      cytotoxicity of HDAC inhibitors in lymphoid malignancies.

PMID- 27890931
TI  - A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma
      models via NK cells and CD4 T cells.
AB  - Anti-CD20 monoclonal antibodies (mAb) such as rituximab have been proven to be
      highly effective at improving outcome in B-cell malignancies. However, many
      patients ultimately relapse and become refractory to treatment. The
      glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced
      antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis and
      direct cell death and was shown to lead to improved outcomes in a randomized
      study in B-CLL. We hypothesized that immune stimulation through Toll-like
      receptor 7 (TLR7) agonism in combination with obinutuzumab would further enhance
      lymphoma clearance and the generation of long-term antitumor immune responses.
      Here we demonstrate, in syngeneic human CD20 (hCD20)-expressing models of
      lymphoma, that systemic administration of a TLR7 agonist (R848) increases
      responses when administered in combination with obinutuzumab and protects against
      disease recurrence. Depletion studies demonstrate that primary antitumor activity
      is dependent on both NK cells and CD4+ T cells but not on CD8+ T cells. However,
      both CD4+ and CD8+ T cells appear necessary for the generation of protective
      immunological memory. Importantly, increased tumor-free survival post
      obinutuzumab and R848 combination therapy was seen in hCD20 transgenic mice,
      which express hCD20 on normal B cells. These findings provide a rationale for
      clinical testing of obinutuzumab in combination with systemically administered
      TLR7 agonists to further improve outcome.

PMID- 27890932
TI  - IL-10 production by CLL cells is enhanced in the anergic IGHV mutated subset and
      associates with reduced DNA methylation of the IL10 locus.
AB  - Chronic lymphocytic leukemias (CLLs) with unmutated (U-CLL) or mutated (M-CLL)
      IGHV have variable features of immunosuppression, possibly influenced by those
      CLL cells activated to produce interleukin 10 (IL-10). The two subsets differ in
      their levels of anergy, defined by low surface immunoglobulin M levels/signaling
      capacity, and in their DNA methylation profile, particularly variable in M-CLL.
      We have now found that levels of IL-10 produced by activated CLL cells were
      highly variable. Levels were higher in M-CLL than in U-CLL and correlated with
      anergy. DNA methylation analysis of IL10 locus revealed two previously
      uncharacterized 'variably methylated regions' (CLL-VMRs1/2) in the gene body, but
      similarly low methylation in the promoter of both U-CLL and M-CLL. CLL-VMR1/2
      methylation was lower in M-CLL than in U-CLL and inversely correlated with IL-10
      induction. A functional signal transducer and activator of transcription 3
      (STAT3) binding site in CLL-VMR2 was confirmed by proximity ligation and
      luciferase assays, whereas inhibition of SYK-mediated STAT3 activation resulted
      in suppression of IL10. The data suggest epigenetic control of IL-10 production.
      Higher tumor load may compensate the reduced IL-10 production in U-CLL,
      accounting for clinical immunosuppression in both subsets. The observation that
      SYK inhibition also suppresses IL-10 provides a potential new rationale for
      therapeutic targeting and immunological rescue by SYK inhibitors in CLL.

PMID- 27890933
TI  - Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra
      terminal protein inhibitor in the therapy of multiple myeloma.
AB  - Inhibition of the bromodomain and extra-terminal (BET) proteins is a promising
      therapeutic strategy for various hematologic cancers. Previous studies suggest
      that BET inhibitors constrain tumor cell proliferation and survival mainly
      through the suppression of MYC transcription and activity. However, suppression
      of the transcription of additional genes also contributes to the antitumor
      activity of BET inhibitors but is less well understood. Here we examined the
      therapeutic potential of CPI-0610, a potent BET inhibitor currently undergoing
      phase I clinical testing, in multiple myeloma (MM). CPI-0610 displays potent
      cytotoxicity against MM cell lines and patient-derived MM cells through G1 cell
      cycle arrest and caspase-dependent apoptosis. CPI-0610-mediated BET inhibition
      overcomes the protective effects conferred by cytokines and bone marrow stromal
      cells. We also confirmed the in vivo efficacy of CPI-0610 in a MM xenograft mouse
      model. Our study found IKZF1 and IRF4 to be among the primary targets of CPI
      0610, along with MYC. Given that immunomodulatory drugs (IMiDs) stabilize
      cereblon and facilitate Ikaros degradation in MM cells, we combined it with CPI
      0610. Combination studies of CPI-0610 with IMiDs show in vitro synergism, in part
      due to concomitant suppression of IKZF1, IRF4 and MYC, providing a rationale for
      clinical testing of this drug combination in MM patients.

PMID- 27890935
TI  - NUP98-fusion transcripts characterize different biological entities within acute
      myeloid leukemia: a report from the AIEOP-AML group.

PMID- 27890937
TI  - Seasonal changes in neophobia and its consistency in rooks: the effect of novelty
      type and dominance position.
AB  - Neophobia, or the fear of novelty, may offer benefits to animals by limiting
      their exposure to unknown danger, but can also impose costs by preventing the
      exploration of potential resources. The costs and benefits of neophobia may vary
      throughout the year if predation pressure, resource distribution or conspecific
      competition changes seasonally. Despite such variation, neophobia levels are
      often assumed to be temporally and individually stable. Whether or not neophobia
      expression changes seasonally and fluctuates equally for all individuals is
      crucial to understanding the drivers, consequences and plasticity of novelty
      avoidance. We investigated seasonal differences and individual consistency in the
      motivation and novelty responses of a captive group of rooks, Corvus frugilegus,
      a seasonally breeding, colonial species of corvid that is known for being
      neophobic. We tested the group around novel objects and novel people to determine
      whether responses generalized across novelty types, and considered whether
      differences in dominance could influence the social risk of approaching unknown
      stimuli. We found that the group's level of object neophobia was stable year
      round, but individuals were not consistent between seasons, despite being
      consistent within seasons. In contrast, the group's avoidance of novel people
      decreased during the breeding season, and individuals were consistent year-round.
      Additionally, although subordinate birds were more likely to challenge dominants
      during the breeding season, this social risk taking did not translate to greater
      novelty approach. Since seasonal variation and individual consistency varied
      differently towards each novelty type, responses towards novel objects and people
      seem to be governed by different mechanisms. Such a degree of fluctuation has
      consequences for other individually consistent behaviours often measured within
      the nonhuman personality literature.

PMID- 27890938
TI  - Chemical kinetic model uncertainty minimization through laminar flame speed
      measurements.
AB  - Laminar flame speed measurements were carried for mixture of air with eight C3-4
      hydrocarbons (propene, propane, 1,3-butadiene, 1-butene, 2-butene, iso-butene, n
      butane, and iso-butane) at the room temperature and ambient pressure. Along with
      C1-2 hydrocarbon data reported in a recent study, the entire dataset was used to
      demonstrate how laminar flame speed data can be utilized to explore and minimize
      the uncertainties in a reaction model for foundation fuels. The USC Mech II
      kinetic model was chosen as a case study. The method of uncertainty minimization
      using polynomial chaos expansions (MUM-PCE) (D.A. Sheen and H. Wang, Combust.
      Flame 2011, 158, 2358-2374) was employed to constrain the model uncertainty for
      laminar flame speed predictions. Results demonstrate that a reaction model
      constrained only by the laminar flame speed values of methane/air flames notably
      reduces the uncertainty in the predictions of the laminar flame speeds of C3 and
      C4 alkanes, because the key chemical pathways of all of these flames are similar
      to each other. The uncertainty in model predictions for flames of unsaturated C3
      4 hydrocarbons remain significant without considering fuel specific laminar
      flames speeds in the constraining target data set, because the secondary rate
      controlling reaction steps are different from those in the saturated alkanes. It
      is shown that the constraints provided by the laminar flame speeds of the
      foundation fuels could reduce notably the uncertainties in the predictions of
      laminar flame speeds of C4 alcohol/air mixtures. Furthermore, it is demonstrated
      that an accurate prediction of the laminar flame speed of a particular C4
      alcohol/air mixture is better achieved through measurements for key molecular
      intermediates formed during the pyrolysis and oxidation of the parent fuel.

PMID- 27890934
TI  - EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic
      leukemia.
AB  - Recurrent mutations within EGR2 were recently reported in advanced-stage chronic
      lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study
      their prognostic impact, 2403 CLL patients were examined for mutations in the
      EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK
      CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490).
      Targeted deep-sequencing of 27 known/postulated CLL driver genes was also
      performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2
      mutations were detected in 91/2403 (3.8%) investigated cases, and associated with
      younger age at diagnosis, advanced clinical stage, high CD38 expression and
      unmutated IGHV genes. EGR2-mutated patients frequently carried ATM lesions (42%),
      TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations
      independently predicted shorter time-to-first-treatment (TTFT) and overall
      survival (OS) in the screening cohort; they were confirmed associated with
      reduced TTFT and OS in the CRC cohort and independently predicted short OS from
      randomization in the UK CLL4 cohort. A particularly dismal outcome was observed
      among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2
      mutations were independently associated with an unfavorable prognosis, comparable
      to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients
      represent a new patient subgroup with very poor outcome.

PMID- 27890936
TI  - Increased proportion of mature NK cells is associated with successful imatinib
      discontinuation in chronic myeloid leukemia.
AB  - Recent studies suggest that a proportion of chronic myeloid leukemia (CML)
      patients in deep molecular remission can discontinue the tyrosine kinase
      inhibitor (TKI) treatment without disease relapse. In this multi-center,
      prospective clinical trial (EURO-SKI, NCT01596114) we analyzed the function and
      phenotype of T and NK cells and their relation to successful TKI cessation.
      Lymphocyte subclasses were measured from 100 imatinib-treated patients at
      baseline and 1 month after the discontinuation, and functional characterization
      of NK and T cells was done from 45 patients. The proportion of NK cells was
      associated with the molecular relapse-free survival as patients with higher than
      median NK-cell percentage at the time of drug discontinuation had better
      probability to stay in remission. Similar association was not found with T or B
      cells or their subsets. In non-relapsing patients the NK-cell phenotype was
      mature, whereas patients with more naive CD56bright NK cells had decreased
      relapse-free survival. In addition, the TNF-alpha/IFN-gamma cytokine secretion by
      NK cells correlated with the successful drug discontinuation. Our results
      highlight the role of NK cells in sustaining remission and strengthen the status
      of CML as an immunogenic tumor warranting novel clinical trials with
      immunomodulating agents.

PMID- 27890940
TI  - Whatever Happened to Formal Methods for Security?
AB  - We asked 7 experts 7 questions to find out what has occurred recently in terms of
      applying formal methods (FM) to security-centric, cyber problems. We are
      continually reminded of the 1996 paper by Tony Hoare "How did Software Get So
      Reliable Without Proof?" [1] In that vein, how did we get so insecure with proof?
      Given daily press announcements concerning new malware, data breaches, and
      privacy loss, is FM still relevant or was it ever? Our experts answered with
      unique personal insights. We were curious as to whether this successful
      methodology in "safety-critical" has succeeded as well for today's "build it,
      hack it, patch it" mindset. Our experts were John McLean (Naval Research Labs),
      Paul Black (National Institute of Standards and Technology), Karl Levitt
      (University of California at Davis), Joseph Williams (CloudEconomist.Com), Connie
      Heitmeyer (Naval Research Labs), Eugene Spafford (Purdue University), and Joseph
      Kiniry (Galois, Inc.). The questions and responses follow.

PMID- 27890939
TI  - The metal face of protein tyrosine phosphatase 1B.
AB  - A new paradigm in metallobiochemistry describes the activation of inactive
      metalloenzymes by metal ion removal. Protein tyrosine phosphatases (PTPs) do not
      seem to require a metal ion for enzymatic activity. However, both metal cations
      and metal anions modulate their enzymatic activity. One binding site is the
      phosphate binding site at the catalytic cysteine residue. Oxyanions with
      structural similarity to phosphate, such as vanadate, inhibit the enzyme with
      nanomolar to micromolar affinities. In addition, zinc ions (Zn2+) inhibit with
      picomolar to nanomolar affinities. We mapped the cation binding site close to the
      anion binding site and established a specific mechanism of inhibition occurring
      only in the closed conformation of the enzyme when the catalytic cysteine is
      phosphorylated and the catalytic aspartate moves into the active site. We discuss
      this dual inhibition by anions and cations here for PTP1B, the most thoroughly
      investigated protein tyrosine phosphatase. The significance of the inhibition in
      phosphorylation signaling is becoming apparent only from the functions of PTP1B
      in the biological context of metal cations as cellular signaling ions. Zinc ion
      signals complement redox signals but provide a different type of control and
      longer lasting inhibition on a biological time scale owing to the specificity and
      affinity of zinc ions for coordination environments. Inhibitor design for PTP1B
      and other PTPs is a major area of research activity and interest owing to their
      prominent roles in metabolic regulation in health and disease, in particular
      cancer and diabetes. Our results explain the apparent dichotomy of both cations
      (Zn2+) and oxyanions such as vanadate inhibiting PTP1B and having insulin
      enhancing ("anti-diabetic") effects and suggest different approaches, namely
      targeting PTPs in the cell by affecting their physiological modulators and
      considering a metallodrug approach that builds on the knowledge of the insulin
      enhancing effects of both zinc and vanadium compounds.

PMID- 27890942
TI  - Removal of Phosphate from Aqueous Solution Using Alginate/Iron (III) Chloride
      Capsules: a Laboratory Study.
AB  - Binding phosphate at participation of alginate/FeCl3 capsules was studied with
      laboratory experiments. The hydrogel microcapsules were obtained with the
      dropping-in method, by gelation of sodium alginate water solution by iron (III)
      chloride solution. Phosphate adsorption characteristics were studied in a static
      batch system with respect to changes in contact time, initial phosphates
      concentration, pH of solution, and temperature. After 24 h of the tests, average
      87.5% of phosphate ions were removed from the natural water solutions; after 48
      h, an equilibrium was reached. The adsorption data were well fit by the
      Freundlich isotherm model. Parameter k of the isotherms amounted from 43.4 to
      104.7, whereas parameter n amounted from 0.362 to 0.476. The course of processes
      of phosphate adsorption and iron desorption to aquatic phase, as well as changes
      in pH, suggests that phosphate adsorption is a major mechanism of phosphate
      removal, whereas simultaneously, but at a much lower degree, a process of
      precipitation of phosphate by iron (III) ions released from the capsules to the
      solution takes its place. Parameters calculated in the Freundlich isotherm
      equation show that by using several times smaller amounts of iron, it is possible
      to remove similar or bigger amounts of phosphorus than with other adsorbents
      containing iron. The alginate/FeCl3 adsorbent removes phosphate in a wide pH
      spectrum-from 4 to 10. Results suggest that the proposed adsorbent has potential
      in remediation of contaminated waters by phosphate.

PMID- 27890943
TI  - Recapitulation of acquired immuno deficiency syndrome associated Kaposi's
      sarcoma.
AB  - Acquired immuno deficiency syndrome (AIDS) associated Kaposi's sarcoma (KS) is
      one of the clinical forms of KS. KS is caused by human herpes viruses 8 or KS
      associated herpes virus (KSHV). In India, till now, only 16 cases of AIDS
      associated KS was reported. Of all the clinical forms of KS, AIDS associated KS
      is distinct in many ways viz.; cutaneous manifestations commonly affects face and
      trunk rather than lower limbs, more mucosal lesions, rapidly progressive, and
      early systemic involvement. When human immunodeficiency virus (HIV) is co
      infected with KSHV, in addition to the other pathogenic factors for the
      development of KS, HIV Tat protein promotes the proliferation of cytokine
      activated endothelial cells and stimulates KS. Moreover, actions of HIV Tat lead
      to the aggressive course of KS in patients with AIDS, compared with the more
      confined behavior of KS in HIV-negative persons. Similarly, latency-associated
      nuclear antigen of KSHV would enhance HIV replication by activating the long
      terminal repeats of HIV-1 through its association with Tat. Effective
      antiretroviral treatment in AIDS associated KS results in reduction of the
      incidence of AIDS-related KS and regression of the existing lesions. Early
      diagnosis and treatment of AIDS associated KS would definitely increase the life
      span and quality of the patients.

PMID- 27890941
TI  - Five-Year Cancer Survival Rates in Oklahoma from 1997 to 2008.
AB  - INTRODUCTION: This study evaluated the five-year observed survival rates of
      American Indians/Alaskan Native, African American, and white cancer patients
      among various demographic characteristics in Oklahoma focusing on lung and
      bronchus, colon and rectum, female breast, and prostate for the cancer patients
      diagnosed between 1997 and 2008. METHODS: The five-year observed survival rates
      were calculated for overall cancer and specific cancer sites, using Kaplan-Meier
      method with data from the Oklahoma Central Cancer Registry. RESULTS: Overall,
      51.5% patients diagnosed with cancer survived for five years. For specific sites
      we found: 79.2% for female breast cancer survived; 77.5% for prostate cancer;
      12.9% for lung and bronchus cancer; and 49.9% for colorectal cancer. CONCLUSIONS:
      The five-year observed survival rates in Oklahoma were consistent with national
      trends. Overall, cancer survival seems to be improving over time, but there
      remains disparity with the AA and AI/AN populations in contrast to whites in
      Oklahoma.

PMID- 27890944
TI  - Role of high-sensitivity C-reactive protein measurements in HIV patients.
AB  - As we herald into the 21st century, the quality of life and the repertoire of
      highly active antiretroviral therapy (HAART) have considerably improved. However,
      considerable work is still needed to educate the population about primary and
      secondary prevention modalities. Moreover, regular monitoring of immune response
      with patients on HAART with conventional biomarkers is still a problem in low
      resource settings which needs to be addressed. We aim to review high-sensitivity
      C-reactive protein as a potential biomarker in this regard.

PMID- 27890945
TI  - Zoon balanitis: A comprehensive review.
AB  - The diagnosis and management of nonvenereal diseases are always a tough challenge
      for the dermatologist due to lack of studies on its diagnostic criteria and
      standard treatment guidelines. Zoon balanitis (ZB) is one of the benign
      nonvenereal dermatoses, which presents as a solitary, persistent erythematous
      plaque usually on the glans penis primarily in the uncircumcised, middle-aged to
      old-aged men. Although it was described by Zoon in 1952, its etiopathogenesis
      still remains hypothetical. This article provides an overview of the
      epidemiology, clinical presentation, histopathological features, and diagnostic
      criteria and diagnostic methods of ZB. In addition to this, it is rather very
      important to differentiate this lesion from its clinical equivocal lesions such
      as erythroplasia of Queyrat, infective and other inflammatory penile dermatoses,
      which has been discussed in this review. The treatment modalities have also been
      reviewed in details, and the importance of circumcision as the treatment of
      choice has been emphasized.

PMID- 27890946
TI  - Prevalence of asymptomatic infections in sexually transmitted diseases attendees
      diagnosed with bacterial vaginosis, vaginal candidiasis, and trichomoniasis.
AB  - BACKGROUND: Sexually transmitted diseases (STD) are a major health problem
      affecting mostly young people in both developing and developed countries. STD in
      women causes both acute morbidity and complications such as infertility, ectopic
      pregnancy, low-birth weight, and prematurity. AIMS: The aim of the study is to
      assess the prevalence of bacterial vaginosis, vaginal candidiasis, and
      trichomoniasis among asymptomatic females attending STD outpatient department in
      a tertiary care hospital in South India. MATERIALS AND METHODS: A retrospective
      analysis of data collected from clinical records of 3000 female patients of age
      18 to 49 over a period of 12 months (July 2014 to June 2015) was carried out at
      the Institute of Venereology, Madras Medical College. Complete epidemiological,
      clinical, and investigational data were recorded and analyzed for the prevalence
      of bacterial vaginosis, vaginal candidiasis, and trichomoniasis among
      asymptomatic patients. RESULTS: About 48.37% (228/470) of bacterial vaginosis
      patients were asymptomatic. Nearly 45.38% (116/235) of vaginal candidiasis
      patients were asymptomatic and 30.35% (26/87) of trichomoniasis patients were
      asymptomatic. The above infections were common in the age group 25-35.
      CONCLUSION: Holistic screening protocol was incorporated for all female patients
      attending STD clinic even if asymptomatic and should be treated accordingly to
      prevent the acquisition of other serious sexually transmitted infections.

PMID- 27890947
TI  - Profile of pneumocystis infection in a tertiary care institute in North India.
AB  - CONTEXT: Pneumocystis jirovecii pneumonia (PcP) is still remains a common
      opportunistic disease in human immunodeficiency virus (HIV) infected individuals.
      Study on PcP in developing countries are scarce. AIMS: To study the occurrence of
      P. jirovecii infection in clinically suspected individuals in a tertiary care
      institute. SETTINGS AND DESIGN: Retrospective study conducted in a tertiary care
      hospital. MATERIALS AND METHODS: Two years data regarding respiratory sample
      analysis, HIV status, and cluster of differentiation 4 (CD4) cell count of
      clinically suspected pneumocystis infection patients with known/unknown HIV
      status were analyzed. RESULTS: Data of 45 eligible patients were analyzed. The
      majority of the patients were male (between 21 and 50 years of age). Total 26
      (57.7%) patients were HIV reactive, of which 14 had CD4 count of <200 cells/mm3.
      20 patients (9 HIV reactive and 11 unknown HIV status) were confirmed with
      pneumocystosis by direct fluorescent antibody (DFA) staining. Four of 14 HIV
      reactive individuals who had CD4 count of <200 cells/mm3 and 5 of 12 HIV reactive
      individuals who had CD4 count of >200 cells/mm3 were positive for pneumocystosis.
      CONCLUSIONS: Pneumocystis pneumonia is still prevalent in North India and is
      mainly affecting patients in economically productive and sexually active age
      group. To diagnose pneumocystosis, DFA is an easily available method in resource
      limited settings. Appreciating the actual HIV or immunodeficiency status and the
      CD4 profile of an individual with symptoms of pneumocystis infection will help
      the clinicians in early diagnosis and initiation appropriate therapy in
      individuals living with the disease.

PMID- 27890948
TI  - Study of infections among human immunodeficiency virus/acquired immunodeficiency
      syndrome patients in Shadan Hospital, Telangana, India.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) pandemicity is a major concern
      today as it causes greater loss of productivity than any other disease. HIV
      infection leads to profound immune deficiency and patients become highly
      susceptible to opportunistic infections (OIs). HIV epidemic in India is
      heterogeneous in nature, both in terms of routes of transmission as well as
      geographical spread. AIMS: (1) Determine prevalence of OIs among HIV-seropositive
      patients and their relation to CD4 count and to focus on the routes of
      transmission. (2) Analyze the route of transmission. METHODS: This is a single
      center prospective study including all the patients attending acquired
      immunodeficiency syndrome (AIDS) care center during the period of January 2014 to
      December 2014. RESULTS: Among 71 patients included in this study, mean age was 30
      years, 57.7% (41 patients) were male, 42.3% (30 patients) were female. Mean CD4
      cell count of the study group was 260.11 and of patients on antiretroviral
      therapy increased subsequently to 553.37 cells/ml. Among the infections, the
      prevalence of candidiasis, tuberculosis (TB), tinea infections, seborrheic
      dermatitis, giardiasis, cryptosporidiosis, and Entamoeba histolytica were 36.6%,
      29.58%, 4.22%, 2.82%, 4.22%, 1.4%, and 1.4%. Most predominant routes were
      heterosexual transmission at 94.3%. It was followed by vertical transmission seen
      in 2.8%. Homosexual transmission is 1.4% and intravenous drug abuse 1.4%.
      CONCLUSION: The frequency of infections among HIV/AIDS patients has got a similar
      linear relation with CD4 cell count. This study reports data will serve as a
      matrix for future evaluation. It is concluded that candidiasis, TB are the most
      common infections in the HIV-seropositive patients in the present study group.

PMID- 27890949
TI  - p16 immunostaining as a predictor of anal and cervical dysplasia in women
      attending a sexually transmitted infection clinic.
AB  - BACKGROUND: Carcinogenesis caused by human papillomavirus (HPV) leads to over
      expression of p16 protein. p16 may act as a marker of HPV integration with host
      genome and serve as a surrogate marker of HPV oncogenesis. MATERIALS AND METHODS:
      A single center study of 75 women (35 HIV-positive and 40 HIV-negative women) was
      conducted. Anal and cervical specimens were obtained for cytology and p16
      immunostaining. RESULTS: The sensitivity of p16 to diagnose anal and cervical
      dysplasia was 50% and 58.8%, respectively, whereas specificity was 98.6% and
      100%, respectively. Positive predictive value for anal and cervical was 75% and
      100%, whereas negative predictive value was 95.8% and 89.2%, respectively. A
      strong relationship between the grade of dysplasia and intensity of p16
      immunoscore was observed (Pearson correlation r = 0.666, P < 0.0001 and r =
      0.496, P < 0.0001 for anal and cervical, respectively). CONCLUSION: p16
      immunostaining with greater specificity for high-grade lesions may improve the
      diagnostic accuracy, especially for high-grade lesions which have a high risk of
      progression to malignancy and thereby necessitate treatment.

PMID- 27890950
TI  - Healthcare-seeking preferences of patients with sexually transmitted infection
      attending a tertiary care center in South Kerala.
AB  - BACKGROUND: Sexually transmitted infections (STIs) are a major public health
      problem in developing countries. These diseases are associated with increased
      risk of transmission of human immunodeficiency virus as well as adverse outcomes
      on pregnancy and reproductive health. Sexual behavior and healthcare-seeking
      behavior are identified as the true risk factors of STIs. METHODS: Hospital-based
      cross-sectional study design was adopted. Eighty-five STI patients were studied
      regarding the inappropriate treatment-seeking behavior, the nature of the first
      point of contact with the health care, the appropriateness of treatment and the
      concerns of the patient regarding the services rendered by government health-care
      facilities. RESULTS: Among the 85 patients studied, 55.3% were males and 44.7%
      were females. Inappropriate treatment-seeking behavior was seen in 29.8% of males
      and 36.8% of females. About 59.6% of males and 81.6% of females sought
      appropriate treatment from modern medicine practitioners before attending our
      institution. Only 7.1% of males and 3.2% of females received appropriate
      treatment. The government sector was the choice of treatment for 46.4% males and
      93.5% females and this difference was statistically significant (P = 0.00081).
      Lack of free medicines, issues of confidentiality, and privacy were the major
      service-related issues in the public sector. CONCLUSION: Appropriate treatment at
      the first point of contact with the health system is an important measure to
      prevent further transmission and development of complications. Health providers
      from both private and public sector should be given frequent periodic training
      regarding syndromic management of STIs and the training should stress on the need
      for risk reduction and condom promotion messages along with medical management.
      Program planners should take necessary steps to ensure adequate and continuous
      supply of free drugs and tackle issues of confidentiality and privacy.

PMID- 27890951
TI  - A situational analysis of sexual and reproductive health issues in physically
      challenged people, attending a tertiary care hospital in New Delhi.
AB  - BACKGROUND AND OBJECTIVES: Physically challenged people constitute the most
      stigmatized sections of society, and are excluded from outreach programs, besides
      being considered sexually inactive. They have unaddressed sexual and reproductive
      healthcare (SRH) issues, predisposing them to sexual abuse and sexually
      transmitted infections (STIs). The huge paucity of data in this field prompted us
      to undertake this study. MATERIALS AND METHODS: A cross-sectional survey was
      conducted on 100 people with more than 40% of permanent disability, attending
      various out/inpatient facilities of a tertiary care hospital in New Delhi, India.
      A structured, pretested questionnaire was used to assess SRH issues. Samples were
      collected from consenting individuals for diagnosis of various STIs, wherever
      relevant. Statistical analysis was done using Pearson's Chi-square test,
      considering significant at P <0.05. RESULTS: Most people were in the age group of
      15-30 years. Limbs were most commonly affected, and the use of assistive devices
      was statistically related to income levels (P = 0.045), 43% was married and 41%
      had children. Contraceptive usage was 33%, with a significant association (P =
      0.03) with education levels. Issues related to sexual health included conditions
      ranging from nerve sensation loss in genitalia to fertility and gynecological
      issues, only 10% had received sexual counseling during rehabilitation. There were
      several misconceptions prevalent regarding HIV and STIs; 35% of the samples
      tested positive for chlamydia IgG. INTERPRETATION AND CONCLUSIONS: This is a
      pioneer study on a grossly neglected issue in India. There is a dire need to
      overcome hurdles and address the SRH issues of physically challenged people to
      achieve the universal WHO goal of "Health for All."

PMID- 27890952
TI  - A study of antiretroviral resistance patterns in treatment experienced and naive
      human immunodeficiency virus infected-patients.
AB  - BACKGROUND: About 10% of the patients had surveillance drug-related mutations for
      nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors
      (PIs) in an Indian study. It was also reported that resistance was maximum for
      nucleoside reverse transcriptase inhibitors (NRTIs) and minimum for PIs. METHODS:
      The present study was a cross-sectional assessment of 21 human immunodeficiency
      virus (HIV)-infected individuals attending a HIV care center in a tertiary care
      center in Mumbai, Maharashtra, India. All HIV-infected individuals included in
      the present analysis were tested for CD4 count, viral load, and resistance to
      antiretrovirals (ARVs). RESULTS: A total of 13 male and 8 female were included in
      the present analysis. Of these, 18 were treatment naive and three were treatment
      experienced patients. In treatment-naive patients, the proportion of high-level
      resistance (HLR) was 2% for NRTIs, 5% for PIs, and 11% for NNRTIs. In treatment
      naive patients, high susceptibility was observed for darunavir (89%) followed by
      lopinavir (72%) and fosamprenavir (67%) among PIs. Similarly, susceptibility was
      high for NRTIs lamivudine (94%), emtricitabine (94%), and tenofovir (89%).
      However, we found HLR for nevirapine (39%) even in treatment-naive patients.
      CONCLUSIONS: The proportion of HLR was relatively low for PIs and NRTIs, compared
      with NNRTIs in treatment-naive patients. We also reported a high correlation in
      resistance patterns among drugs belonging to the same group. Thus, it may be
      useful to conduct ARV resistance even in newly infected HIV patients and those
      receiving medications for the first time.

PMID- 27890953
TI  - Knowledge, attitude, and perception of disease among persons living with human
      immunodeficiency virus/acquired immuno deficiency syndrome: A study from a
      tertiary care center in North India.
AB  - BACKGROUND: Although modification of behavioral practices among human
      immunodeficiency virus (HIV)-affected patients is important in decreasing HIV
      disease transmission, the knowledge, attitude, and perception studies about HIV
      infection rarely include persons living with HIV/acquired immuno deficiency
      syndrome (AIDS). AIMS: To assess knowledge, attitude, and perceptions of persons
      living with HIV/AIDS for the disease and other epidemiological aspects. MATERIALS
      AND METHODS: One-hundred and fifty consecutive persons living with HIV/AIDS were
      enrolled for this questionnaire-based cross-sectional, descriptive study.
      RESULTS: These 150 patients comprised 93 men and 57 women, aged between 14 and 78
      (mean 37.13) years. The majority, 112 (74.67%) patients were between 20 and 50
      years of age and 116 (77.3%) patients were either illiterate or high-school
      dropouts. Drivers, laborers, and self-employed comprised 69 (74.2%) patients
      among affected males. Only 129 (86%) respondents had heard about HIV/AIDS and
      knew about its heterosexual transmission. Ninety-eight (65.3%) respondents were
      aware of disease transmission from infected blood or needle pricks.
      Interestingly, 106 (70.7%) respondents were aware of the importance of using
      condom in preventing disease transmission. Television/radio was the most common
      sources of information for 135 (90%) patients. Nearly, 69% respondents disfavored
      disclosing their disease to friends/colleagues fearing stigmatization.
      CONCLUSIONS: Information, education, and communication activities are imperative
      to educate persons living with HIV/AIDS about life-long nature of the disease,
      modes of its transmission, and significance of preventive measures to bridge the
      gaps in their knowledge. While improvement in individual economic status,
      education, and health services remains highly desirable, mass media can play a
      pivotal role in creating awareness among masses.

PMID- 27890954
TI  - Prevalence of Vitamin B12 and folic acid deficiency in HIV-positive patients and
      its association with neuropsychiatric symptoms and immunological response.
AB  - BACKGROUND: Deficiency of micronutrients is prevalent even before the development
      of symptoms of HIV disease and is associated with accelerated HIV disease
      progression. AIMS: This study evaluates the prevalence of folate and Vitamin B12
      deficiency in HIV-positive patients with or without tuberculosis (TB) and its
      association with neuropsychiatric symptoms and immunological response. SETTINGS
      AND DESIGN: Cross-sectional, observational study in an outpatient setting.
      PATIENTS AND METHODS: Four groups of HIV-positive patients with TB (Group I), HIV
      positive patients with neuropsychiatric symptoms (Group II), HIV-positive
      patients without neuropsychiatric symptoms or TB (Group III), and HIV-negative
      controls with neuropsychiatric symptoms (Group IV). Vitamin B12 and folate
      estimation was done using carbonyl metallo-immunoassay method. STATISTICAL
      ANALYSIS USED: ANOVA, Kruskal-Wallis and Mann-Whitney, Pearson's correlation.
      RESULTS: The prevalence of folic acid deficiency was 27.1% in the Group I, 31.9%
      in the Group II, 23.4% in the Group III, and 32% in the Group IV being higher in
      patients with neuropsychiatric symptoms in both HIV and non-HIV patients. The
      prevalence of Vitamin B12 deficiency was 18.8% in Group I, 9.1% in Group II, 4.8%
      in Group III, and 16.7% in Group IV. The patients with folate deficiency had more
      severe depression and anxiety. CONCLUSION: Nearly, 30% of the HIV patients had a
      folic acid deficiency, and about 10% of the HIV patients had Vitamin B12
      deficiency. The folate deficiency was highest among neuropsychiatric patients
      with or without HIV infection and Vitamin B12 deficiency was higher among HIV
      patients with TB.

PMID- 27890955
TI  - Aspergillus meningoencephalitis in a patient with human immunodeficiency virus
      infection: Normal cerebrospinal fluid does not mean absence of meningitis.
AB  - A male with human immunodeficiency virus infection presented with febrile
      encephalopathy followed by seizures and left hemiparesis. Initial imaging with
      contrast computerized tomography (CT) scan brain and cerebrospinal fluid (CSF)
      examination were normal. Subsequent magnetic resonance imaging brain revealed
      bilateral parieto-occipital infarcts with bleed. He did not improve on treatment
      with broad-spectrum antibiotics, anti-tubercular drugs, and antifungals. He
      finally succumbed to the disease. His CSF culture grew Aspergillus after 2 weeks.
      Central nervous system (CNS) aspergillosis can present with variable
      presentations, and initial CT scan and CSF examination can be normal, especially
      in the immunosuppressed. High index of suspicion is required for the diagnosis of
      invasive CNS Aspergillus in the immunosuppressed.

PMID- 27890956
TI  - Protein S and protein C deficiency with multiple infarcts in a human
      immunodeficiency virus-infected female child.
AB  - Thrombotic episodes have occurred in patients with human immunodeficiency virus
      (HIV) infection, and various abnormalities leading to hypercoagulable state have
      been reported. However, multiple cerebral infarctions in an HIV-infected child
      along with protein S and protein C deficiency are rare. We report such a case in
      an antiretroviral therapy-naive HIV-infected female child.

PMID- 27890957
TI  - Unusual presentation of mucocutaneous leishmaniasis in HIV-infected patient.
AB  - Leishmaniasis is caused by protozoan parasite of genus leishmania. Visceral
      leishmaniasis, diffuse cutaneous leishmaniasis, and atypical forms of cutaneous
      leishmaniasis are common in HIV-infected patients. Our patient presented with an
      obstructive mass in nasal cavity and was diagnosed as a case of mucocutaneous
      leishmaniasis. Spontaneous healing of lesions in HIV-infected patients is rare
      rather they are unresponsive to treatment and have frequent relapses, especially
      in patients with low CD4 count. However, in our patient, the lesion improved
      significantly after 2 months of highly active antiretroviral therapy and co
      trimoxazole prophylaxis.

PMID- 27890958
TI  - Nonhealing genital ulcer in AIDS: A diagnostic dilemma!
AB  - HIV/AIDS-related immune alteration poses many diagnostic and therapeutic
      challenges. HIV-positive 44-year-old male, on second-line antiretroviral therapy
      (ART) presented with asymptomatic non healing, well-defined, erythematous ulcer
      over penis since 8 months with serosanguinous discharge. Inguinal lymph nodes
      were not palpable. Tzanck smear was negative. Biopsy was not done as the patient
      was not willing for the same. Acyclovir was given considering herpes infection to
      which there was no response, and hence azithromycin and metronidazole were given,
      without improvement. Minocycline was given to take care of possible atypical
      mycobacterial infection. Due to lack of response, corticosteroid was given for 2
      weeks keeping in mind possibility of vasculitis, but there was no improvement.
      Although investigations to rule out tuberculous etiology were negative, empirical
      anti-Koch's therapy Category 2 was given without response even after 3 months.
      Finally, a biopsy was taken from lesion which was suggestive of donovanosis.
      Trimethoprim Sulfamethoxazole in higher dose was started to which he responded
      after 2 weeks, and therapy was continued till complete response. Patient is on
      second-line ART for last 7 years. He is clinically stable, but his CD4 count is
      hovering at around 250-300 suggestive of ART failure. Virological evaluation was
      not feasible. Diagnostic challenges posed include possibility of resistant
      bacterial, viral infection, vasculitis, or drug reaction in a setting of probable
      ART failure.

PMID- 27890959
TI  - Anti-retroviral therapy's miracle in the treatment of Bowen's disease in a human
      immunodeficiency virus-positive patient: A rare case report.
AB  - Bowen's disease (BD) is a form of squamous cell carcinoma in situ often
      associated with human papillomavirus. Co-infection with human immunodeficiency
      virus (HIV) is associated with a greater risk of malignancy. We describe a case
      of BD in a 52-year-old unmarried HIV-positive male who presented with extensive
      skin lesions of 1-year duration. Histopathology was suggestive of BD. He had been
      tried with topical imiquimod cream and cryo-therapy for 6 months. We observed no
      response for these above therapies. He was started on with anti-retroviral
      therapy (ART) as his CD4 count was 253 cells/mm3. The entire cutaneous lesions
      completely disappeared within 6 months of ART, which was an interesting
      incidence.

PMID- 27890960
TI  - Cryptococcal lymphadenitis in a human immunodeficiency virus-infected patient: A
      diagnostic role of fine needle aspiration cytology and special stains.

PMID- 27890961
TI  - Circumcision: Viable treatment option for resistant genital warts.

PMID- 27890962
TI  - Neurokinin-1 receptor antagonists: A new revolution in antiretroviral treatment?

PMID- 27890963
TI  - Successful management of recalcitrant perianal warts with two sessions of
      intralesional 5-fluorouracil.

PMID- 27890964
TI  - Association of the MDM2 SNP285 Polymorphism with Cancer Susceptibility: A Meta
      Analysis.
AB  - The mouse double minute 2 (MDM2) gene encodes a negative regulator for p53, and
      the polymorphism SNP285 in the promoter region of MDM2 gene has been implicated
      in cancer risk, but individual published studies had inconclusive results.
      Therefore, we performed this meta-analysis to obtain a more precise estimation
      between MDM2 SNP285 polymorphism and risk of cancer. A systematic literature
      search was performed using the PubMed, Embase, and Chinese Biomedical (CBM)
      databases. Ultimately, 16 published studies comprising 14,573 cases and 9,115
      controls were included. Pooled odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated to assess the strength of associations. Overall, MDM2
      SNP285 polymorphism was significantly associated with a decreased overall cancer
      risk with the heterozygous model (OR = 0.89, 95% CI = 0.79-0.99), and reduced ORs
      were observed with other genetic models (dominant: OR = 0.90, 95% CI = 0.79-1.01
      and allele comparison: OR = 0.91, 95% CI = 0.80-1.03) but not reaching
      statistical significance. Stratification analysis indicated a decreased risk for
      ovarian cancer, Caucasians, and studies with relatively large sample size.
      Despite some limitations, this meta-analysis indicated that the MDM2 SNP285
      polymorphism was associated with a decreased cancer risk, which warrants further
      validation in large and well-designed studies.

PMID- 27890965
TI  - BEESCOUT: A model of bee scouting behaviour and a software tool for
      characterizing nectar/pollen landscapes for BEEHAVE.
AB  - Social bees are central place foragers collecting floral resources from the
      surrounding landscape, but little is known about the probability of a scouting
      bee finding a particular flower patch. We therefore developed a software tool,
      BEESCOUT, to theoretically examine how bees might explore a landscape and
      distribute their scouting activities over time and space. An image file can be
      imported, which is interpreted by the model as a "forage map" with certain
      colours representing certain crops or habitat types as specified by the user.
      BEESCOUT calculates the size and location of these potential food sources in that
      landscape relative to a bee colony. An individual-based model then determines the
      detection probabilities of the food patches by bees, based on parameter values
      gathered from the flight patterns of radar-tracked honeybees and bumblebees.
      Various "search modes" describe hypothetical search strategies for the long-range
      exploration of scouting bees. The resulting detection probabilities of forage
      patches can be used as input for the recently developed honeybee model BEEHAVE,
      to explore realistic scenarios of colony growth and death in response to
      different stressors. In example simulations, we find that detection probabilities
      for food sources close to the colony fit empirical data reasonably well. However,
      for food sources further away no empirical data are available to validate model
      output. The simulated detection probabilities depend largely on the bees' search
      mode, and whether they exchange information about food source locations.
      Nevertheless, we show that landscape structure and connectivity of food sources
      can have a strong impact on the results. We believe that BEESCOUT is a valuable
      tool to better understand how landscape configurations and searching behaviour of
      bees affect detection probabilities of food sources. It can also guide the
      collection of relevant data and the design of experiments to close knowledge
      gaps, and provides a useful extension to the BEEHAVE honeybee model, enabling
      future users to explore how landscape structure and food availability affect the
      foraging decisions and patch visitation rates of the bees and, in consequence, to
      predict colony development and survival.

PMID- 27890967
TI  - Airborne pollen and fungal spores in Garki, Abuja (North-Central Nigeria).
AB  - The ambient atmosphere is dominated with pollen and spores, which trigger
      allergic reactions and diseases and impact negatively on human health. A survey
      of pollen and fungal spores constituents of the atmosphere of Garki, Abuja (North
      Central Nigeria) was carried out for 1 year (June 1, 2011-May 31, 2012). The aim
      of the study was to determine the prevalence and abundance of pollen and fungal
      spores in the atmosphere and their relationship with meteorological parameters.
      Airborne samples were trapped using modified Tauber-like pollen trap, and the
      recipient solutions were subjected to acetolysis. Results revealed the abundance
      of fungal spores, pollen, fern spores, algal cysts and diatoms in decreasing
      order of dominance. The atmosphere was qualitatively and quantitatively dominated
      by pollen during the period of late rainy/harmattan season than the rainy season.
      Numerous fungal spores were trapped throughout the sampling periods among which
      Alternaria spp., Fusarium spp., Cladosporium spp. and Curvularia spp. dominated.
      These fungi have been implicated in allergic diseases and are dermatophytic,
      causing diverse skin diseases. Other pathogenic fungi found in the studied
      aeroflora were Dreschlera spp., Helminthosporium spp., Torula spp., Pithomyces
      spp., Tetraploa spp., Nigrospora ssp., Spadicoides spp., Puccinia spp. and
      Erysiphe graminis. Total pollen and fungal spores counts do not show significant
      correlation with meteorological parameters.

PMID- 27890966
TI  - Climate change effects on airborne pathogenic bioaerosol concentrations: a
      scenario analysis.
AB  - The most recent IPCC report presented further scientific evidence for global
      climate change in the twenty-first century. Important secondary effects of
      climate change include those on water resource availability, agricultural yields,
      urban healthy living, biodiversity, ecosystems, food security, and public health.
      The aim of this explorative study was to determine the range of expected airborne
      pathogen concentrations during a single outbreak or release in a future climate
      compared to a historical climatic period (1981-2010). We used five climate
      scenarios for the periods 2016-2045 and 2036-2065 defined by the Royal
      Netherlands Meteorological Institute and two conversion tools to create hourly
      future meteorological data sets. We modelled season-averaged airborne pathogen
      concentrations by means of an atmospheric dispersion model and compared these
      data to historical (1981-2010) modelled concentrations. Our results showed that
      modelled concentrations were modified several percentage points on average as a
      result of climate change. On average, concentrations were reduced in four out of
      five scenarios. Wind speed and global radiation were of critical importance,
      which determine horizontal and vertical dilution. Modelled concentrations
      decreased on average, but large positive and negative hourly averaged effects
      were calculated (from -67 to +639 %). This explorative study shows that further
      research should include pathogen inactivation and more detailed probability
      functions on precipitation, snow, and large-scale circulation.

PMID- 27890968
TI  - Pollen nightmare: elevated airborne pollen levels at night.

PMID- 27890969
TI  - BEHAVIOR OF POST-INSTALLED ANCHORS TESTED BY STEPWISE INCREASING CYCLIC LOAD
      PROTOCOLS.
AB  - Cyclic loads are a characteristic feature of actions acting on structures and
      anchorages during earthquakes. For this reason, seismic qualification of post
      installed concrete anchors according to the internationally recognized American
      Concrete Institute (ACI) standard ACI 355 is based on cyclic load tests. The
      protocols for these tests, however, have limited scientific basis. Therefore, in
      the present paper newly-developed test protocols with stepwise-increasing load
      amplitudes are utilized to more realistically evaluate anchor seismic
      performance. The study focuses on the load-displacement behavior of common anchor
      types installed in cracked concrete and subjected to both cyclic tension and
      cyclic shear actions. The results confirmed robust behavior for anchors loaded in
      cyclic tension even in the presence of crack widths in the anchorage material
      larger than currently required by ACI 355. In addition, the critical influence of
      low cycle fatigue on the performance of anchors loaded in cyclic shear is
      demonstrated.

PMID- 27890970
TI  - Enterococcus faecium HDRsEf1 Protects the Intestinal Epithelium and Attenuates
      ETEC-Induced IL-8 Secretion in Enterocytes.
AB  - The probiotic Enterococcus faecium HDRsEf1 (Ef1) has been shown to have positive
      effects on piglet diarrhoea, but the mechanism has not yet been elucidated. In
      this study, using the IPEC-J2 cell line to mimic intestinal epithelial cells and
      enterotoxigenic Escherichia coli (ETEC) K88ac as a representative intestinal
      pathogen, the mechanism underlying Ef1 protection against an enteropathogen was
      investigated. The results demonstrated that Ef1 was effective in displacing K88ac
      from the IPEC-J2 cell layer. Moreover, Ef1 and its cell-free supernatant (S-Ef1)
      modulate IL-8 released by IPEC-J2 cells. Ef1 and its cell-free supernatant showed
      the potential to protect enterocytes from an acute inflammatory response. In
      addition, Ef1 and its cell-free supernatant increased the transepithelial
      electrical resistance (TEER) of the enterocyte monolayer, thus strengthening the
      intestinal barrier against ETEC. These results may contribute to the development
      of therapeutic interventions using Ef1 in intestinal disorders of piglets.

PMID- 27890971
TI  - Veronicastrum axillare Alleviates Lipopolysaccharide-Induced Acute Lung Injury
      via Suppression of Proinflammatory Mediators and Downregulation of the NF-kappaB
      Signaling Pathway.
AB  - Veronicastrum axillare is a traditional medical plant in China which is widely
      used in folk medicine due to its versatile biological activities, especially for
      its anti-inflammatory effects. However, the detailed mechanism underlying this
      action is not clear. Here, we studied the protective effects of V. axillare
      against acute lung injury (ALI), and we further explored the pharmacological
      mechanisms of this action. We found that pretreatment with V. axillare suppressed
      the release of proinflammatory cytokines in the serum of ALI mice. Histological
      analysis of lung tissue demonstrated that V. axillare inhibited LPS-induced lung
      injury, improved lung morphology, and reduced the activation of nuclear factor
      kappaB (NF-kappaB) in the lungs. Furthermore, the anti-inflammatory actions of V.
      axillare were investigated in vitro. We observed that V. axillare suppressed the
      mRNA expression of interleukin-1beta (IL-1beta), IL-6, monocyte chemotactic
      protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF
      alpha) in RAW264.7 cells challenged with LPS. Furthermore, pretreatment of V.
      axillare in vitro reduced the phosphorylation of p65 and IkappaB-alpha which is
      activated by LPS. In conclusion, our data firstly demonstrated that the anti
      inflammatory effects of V. axillare against ALI were achieved through
      downregulation of the NF-kappaB signaling pathway, thereby reducing the
      production of inflammatory mediators.

PMID- 27890973
TI  - A Dedicated Public Health Cadre: Urgent and Critical to Improve Health in India.

PMID- 27890972
TI  - What, Me Worry and Ruminate About DSM-5 and RDoC? The Importance of Targeting
      Negative Self-Referential Processing.
AB  - Rumination, worry, and other forms of negative self-referential processing (NSRP)
      are familiar to everyone, as reflecting on the self is perhaps our most human
      characteristic. However, for a substantial subgroup of patients, NSRP arises in
      response to intense emotionality, worsening the clinical presentation, and
      diminishing the treatment response. The combination of emotionality and NSRP
      likely reflects an endophenotype of complicated and treatment refractory patients
      who fail to achieve a satisfactory treatment response in our trials and our
      clinics. An important next step is to personalize treatments by deliberately
      targeting NSRPs within established treatment protocols or in as yet novel
      treatments. Enriching treatments with mindfulness meditation is one possible
      avenue for personalized care of patients with this hypothesized endophenotype.

PMID- 27890974
TI  - Senior Friendly Hospitals: Development and Application of Criteria: A Descriptive
      Study.
AB  - BACKGROUND: The world's population is rapidly aging. Between 2000 and 2050, the
      proportion of the world's population over the age of 60 will double from about
      11% to 22%; more so in the developing countries. The prevalence of frailty and
      morbidity among the elderly is high. There is a need to assess the "preparedness"
      of the health care system including hospitals to respond to the needs of the
      elderly. AIM: 1. To develop criteria for a senior friendly hospital and 2. To
      assess the feasibility of application of these criteria. MATERIALS AND METHODS: A
      descriptive study was done at Bangalore, India, involving 100 subjects sampled by
      purposive sampling. Study population consisted of senior citizens, their
      caretakers, physicians, hospital support staff, nurses, geriatricians, hospital
      administrators, and architects. They were interviewed using a validated
      translated interview schedule. The study consisted of two phases; Phase 1:
      Developing a checklist to assess senior friendliness of a hospital by using
      modified Delphi technique. Phase 2: Application of the checklist thus developed
      to selected hospitals in order to assess the feasibility of administration. The
      data was then analyzed using Statistical Package for the Social Sciences (SPSS)
      for frequencies, proportions, central tendency and dispersion, interclass
      reliability, intraclass reliability, and Cronbach's alpha. RESULTS: A checklist
      containing 44 items to assess the senior friendliness of a hospital was
      developed. The checklist was found feasible and easy to administer. CONCLUSIONS:
      The checklist thus developed to assess senior friendliness of a hospital has
      wider application as it has a potential to be considered for framing senior
      friendly hospital guidelines/policies.

PMID- 27890975
TI  - Prevalence of Type 2 Diabetes Mellitus among Urban Sikh Population of Amritsar.
AB  - CONTEXT: Type 2 Diabetes Mellitus (T2DM) refers to a group of common metabolic
      disorders that share the phenotype of Hyperglycemia. More than 60% of the world's
      population with diabetes comes from Asia. AIM: To study the prevalence of Type 2
      Diabetes Mellitus among Sikh individuals living in the urban localities of
      Amritsar. SETTINGS AND DESIGN: The study was designed in the Faculty of Sports
      Medicine & Physiotherapy, Guru Nanak Dev University, Amritsar, Punjab, India. The
      data collection was carried out in various urban localities of Amritsar. Blood
      samples were analyzed in the Biochemistry laboratory, whereas data analysis and
      article preparation was carried out in the Faculty of Sports Medicine and
      Physiotherapy. MATERIALS AND METHODS: Multi-stage random sampling was done with a
      sample size of 1089 patients. STATISTICAL ANALYSIS: The data was analyzed in
      Stata 11.2 software. Various tests used in the study are Mean +/- SD, Pearson Chi
      Square Test, Students' t test and multiple logistic regression test. RESULTS: Our
      study showed that the prevalence rate of Type 2 Diabetes Mellitus is 23.2% with
      the confidence interval of 20.7-25.7. Proportionately more patients with T2DM had
      hypertension (46.6%). Likewise proportionately more patients, 67.5% had
      hypertrigylerdemia, 67.6% had low HDL levels, 59.2 % had hypercholesterolemia and
      73.1% suffered from metabolic syndrome. CONCLUSIONS: Our study clearly indicates
      that the young Sikh adults below 40 years of age have similar high BMI, WC and
      WHR to that of the older adults above 40 years of age. It is necessary to adopt
      appropriate preventive strategies and interventions in high-risk individuals to
      curb the growing epidemic of diabetes. Innovative community outreach programs
      need to be designed and implemented to create awareness and early screening and
      treatment of diabetes, especially in the urban population.

PMID- 27890976
TI  - Study Frequency of Hypertension and Obesity and their Relationship with Lifestyle
      Factors (Nutritional Habits, Physical Activity, Cigarette Consumption) in Ardabil
      City Physicians, 2012-13.
AB  - BACKGROUND AND OBJECTIVE: Few studies have been done on lifestyle of Iranian
      physicians. As physicians have important role in health promotion, the main goal
      of the study was to assess the lifestyle of this influential group. MATERIALS AND
      METHODS: A cross-sectional descriptive study was conducted on lifestyle of all
      registered physicians of Ardabil hospitals, Iran, 2012-13. In this research, 225
      physicians were selected, by using simple random sampling. Demographic and
      lifestyle data were obtained by self-report using standard questionnaires,
      physical activity by official Iranian short-version of the international physical
      activity questionnaire, and dietary intake by food frequency questionnaire.
      Weight and height was performed according to standard protocols by using
      standardized and zero calibrated instruments. Data were analyzed by inferential
      statistics using Statistical Package for the Social Sciences. 16 software.
      RESULTS: Findings showed that 8% of participants were hypertensive, 21.3% smoker,
      40%-47% inactive, 51.1% overweight, and 18.2% obese. There was a significant
      relationship between blood pressure and self-reported lifestyle habits (P <
      0.05). And 70.7% of males and 74.1% of females had regular 10-min walking each
      day and moderate activity of males was significantly higher than females (P <
      0.05). Food frequency weekly consumption of overweight and obese physicians were
      significantly higher than normal weight physicians (P < 0.05). CONCLUSION: Few
      doctors follow a healthy lifestyle; this may have a negative effect on society
      attitude about health.

PMID- 27890977
TI  - Health and Socioeconomic Status of the Elderly People Living in Hilly Areas of
      Pakhribas, Kosi Zone, Nepal.
AB  - BACKGROUND: The rising geriatric population is facing significant health and
      social problems in the developing world that are impacting the quality of their
      lives. OBJECTIVE: The study describes the general health status and the
      socioeconomic characteristics of the elderly people of Pakhribas village
      development committee (VDC) of Eastern Nepal. MATERIALS AND METHODS: Descriptive
      cross-sectional study was carried out targeting the people aged 60 years and
      above in the sample area using a semi-structured questionnaire and convenient
      sampling to get the required sample size. A total of 189 elderly people who
      consented were interviewed in May 2010. RESULT: The major part of the elderly
      population was in the age group of 60-69 years. Seventy-two percent were
      illiterate and 75% were still earning with the majority involved in farming. Nine
      out of ten were living with their families and still made decisions for the
      household, Eighty-two percent did not feel lonely and 88.4% did not report any
      misbehavior by the house members. Regarding health, 69% had some diagnosed health
      issue with 36% suffering from gastritis and 20.4% from chronic lung disease.
      Using the ICD 10 criteria, depression was found among 18%. The most prevalent
      geriatric problem was a dental problem as found in 61% even though 87% claimed to
      brush their teeth regularly. More than half were suffering from visual difficulty
      and the proportions suffering from memory and hearing issues were also
      substantive. Smoking habit was found in 60%, and the relation between smoking and
      chronic respiratory diseases had a statistical association (P = <0.05). The
      geriatric cases who were misbehaved with felt depressed or neglected in the
      family (P = <0.0001). CONCLUSIONS: The results of the study show that employment,
      family support, and pension schemes have a positive impact on the social status
      of the elderly. Health screening clinics should be established in the community
      to detect health-related disorders. Elderly populations need health education to
      emphasize the importance of personal and dental hygiene and to abstain from
      smoking and alcohol.

PMID- 27890979
TI  - Comprehensive Index for Community Health Assessment of Typical District
      Administrative Units in Maharashtra State, India.
AB  - BACKGROUND: Health administrators require status of health of different
      administrative units under them. Use of large number of indicators may create
      confusion and uncertainty about health status. Availability of a comprehensive
      index is certainly useful. OBJECTIVE: To evolve one comprehensive health index
      for a district as unit and measure district wise disparity. MATERIALS AND
      METHODS: Ten indicators from categories of health outcomes, health system,
      determinants of health, and utilization of services were considered. Data for
      districts in Maharashtra State were obtained from different sources.For each
      indicator the best performing district was given score of 100 and other districts
      were given marks proportionately. RESULTS: The comprehensive index for the state
      was 0.52. The district scoring lowest value of 0.36 was a tribal district and
      scoring highest value of 0.66 was a nontribal district. CONCLUSION: Computing
      such index of districts for monitoring and allocation of resources may be useful
      managerial tool.

PMID- 27890978
TI  - Patterns of Use and Perceptions of Harm of Smokeless Tobacco in Navi Mumbai,
      India and Dhaka, Bangladesh.
AB  - BACKGROUND: Globally, smokeless tobacco use is disproportionately concentrated in
      low-income and middle-income countries like India and Bangladesh. OBJECTIVES: The
      current study examined comparative patterns of use and perceptions of harm for
      different smokeless tobacco products among adults and youth in Navi Mumbai,
      India, and Dhaka, Bangladesh. METHODS: Face-to-face interviews were conducted on
      tablets with adult (19 years and older) smokeless tobacco users and youth (16-18
      years) users and non-users in Navi Mumbai (n = 1002), and Dhaka (n = 1081).
      RESULTS: A majority (88.9%) of smokeless tobacco users reported daily use.
      Approximately one-fifth (20.4%) of the sample were mixed-users (used both smoked
      and smokeless tobacco), of which about half (54.4%) reported that they primarily
      used smokeless over smoked forms like cigarettes or bidis. The proportion of
      users planning to quit was higher in India than in Bangladesh (75.7% vs. 49.8%, p
      < 0.001). Gutkha was the most commonly used smokeless product in India, and pan
      masala in Bangladesh. Among users in Bangladesh, the most commonly reported
      reason for using their usual product was the belief that it was "less harmful"
      than other types. Perceptions of harm also differed with respect to a
      respondent's usual product. Bangladeshi respondents reported more negative
      attitudes toward smokeless tobacco compared to Indian respondents. CONCLUSIONS:
      The findings highlight the high daily use of smokeless tobacco, and the high
      prevalence of false beliefs about its harms. This set of findings reinforces the
      need to implement effective tobacco control strategies in low and middle-income
      countries like India and Bangladesh.

PMID- 27890980
TI  - BMI is a Better Indicator of Cardiac Risk Factors, as against Elevated Blood
      Pressure in Apparently Healthy Female Adolescents and Young Adult Students:
      Results From a Cross-Sectional Study in Tripura.
AB  - BACKGROUND: Anthropometric measures are used as indicators of elevated blood
      pressure, but reported to have variable sensitivity among populations. This study
      was undertaken to identify the better indicator of Cardiac-risk factors by
      statistical comparison of BMI, Waist circumference, and Waist to Height (WtHr)
      ratio in apparently healthy adolescents and young adult female students of
      Tripura. MATERIALS AND METHODS: A cross-sectional study was conducted in a
      resource limited setup on 210 apparently healthy female adolescents and young
      adult students in Tripura. Mean (+/-SD) of all parameters were compared (ANOVA)
      to recognize significant independent (anthropometric measures) and dependent
      factors (blood pressure indices and so on). Correlation (r) analysis was used to
      identify the better (p) indicator of blood pressure indices (dependent variable)
      and its impact was assessed by Multiple Regression analysis. RESULTS: blood
      pressure indices are comparatively higher in obese and overweight participants
      with statistically significant (95.5% confidence) mean differences. Significant
      correlation with dependent factors is observed with BMI followed by WtHr and
      Waist Circumference. Impact of anthropometric measures with blood pressure
      Indices is most significant for BMI (P <= 0.020) followed by WtHr (P <= 0.500)
      and waist circumference (P <= 0.520). CONCLUSION: BMI is a superior indicator of
      blood pressure indices and can identify participants at risk even in apparently
      healthy adolescent and young adult females.

PMID- 27890981
TI  - Neonatal Cholestasis - Single Centre Experience in Central India.
AB  - BACKGROUND: Neonatal cholestasis syndrome (NCS) is a major cause of morbidity and
      mortality in infants. The disorder has rarely been studied in centers from
      Central India. OBJECTIVES: To study the prevalence, clinical presentation and
      etiology of NCS at a tertiary referral center in Central India. MATERIALS AND
      METHODS: The study was carried out at a tertiary referral center in Central
      India. The study is a descriptive study. The records of all patients with
      suspected NCS treated in the Department of Pediatrics from 2007-2012 were
      analyzed. RESULTS: One hundred and sixty-eight children had a provisional
      diagnosis of NCS. The complete records of 100 children were available for the
      study. The median age of presentation was 78 days (range 15-270 days). The male:
      female ratio was 1.17:1. The clinical features noted were- jaundice
      (100/100,100%), failure to thrive (73,73%), organomegaly (68, 68%), acholic
      stools (38,38%), abdominal distention (52,52%) and poor feeding (29, 29%). The
      etiology as confirmed by investigations is as follows- neonatal hepatitis
      (20,20%), idiopathic neonatal hepatitis (18,18%), biliary atresia (41,41%),
      sepsis (14,14%) and others (7,7%). CONCLUSIONS: The proportion of NCS in our
      group of patients was 1.2 per 1000 patients. Jaundice, organomegaly and failure
      to thrive are the common presentations. Biliary atresia, neonatal hepatitis and
      idiopathic neonatal hepatitis were the common etiological factors at our center.

PMID- 27890982
TI  - Towards a Better Health Care Delivery System: The Tamil Nadu model.
AB  - The Tamil Nadu model of public health is renowned for its success in providing
      quality health services at an affordable cost especially to the rural people.
      Tamil Nadu is the only state with a distinctive public health cadre in the
      district level and also the first state to enact a Public Health Act in 1939.
      Tamil Nadu has gained significant ground in the various aspects of health in the
      last few decades largely because of the significant reforms in its health sector
      which dates back to 1980s which saw rigorous expansion of rural health
      infrastructure in the state besides deployment of thousands of multipurpose
      health workers as village health nurses in rural areas. Effective implementation
      of Universal Immunization Programme, formation of Tamil Nadu Medical Services
      Corporation for regulating the drug procurement and promoting generic drugs,
      early incorporation of indigenous system of medicine into health care service,
      formulation of a health policy in 2003 by the state with special emphasis on low
      income, disadvantaged communities alongside efficient implementation of The Tamil
      Nadu Health Systems Project (TNHSP) are the major factors which contributed for
      the success of the state. The importance of good political commitment and
      leadership in the health gains of the state warrants special mention. Moreover,
      the economic growth of the state, improved literacy rate, gender equality, and
      lowered fertility rate in the last few decades and contributions from the private
      sector have their share in the public health success of the state. In spite of
      some flaws and challenges, the Tamil Nadu Model remains the prototype health care
      delivery system in resource-limited settings which can be emulated by other
      states also toward a better health care delivery system.

PMID- 27890983
TI  - Child Marriage in Rural Gujarat.

PMID- 27890984
TI  - Child Rearing Practices Amongst Brothel-based Commercial Sex Workers.
AB  - [This retracts the article on p. 197 in vol. 37, PMID: 23112449.].

PMID- 27890985
TI  - Interstitial lung disease (ILD) in India: Insights and lessons from the
      prospective, landmark ILD-India registry.

PMID- 27890987
TI  - A search for covert precipitating clinical parameters in frequent exacerbators of
      chronic obstructive pulmonary disease.
AB  - INTRODUCTION: Acute exacerbations are a significant source of morbidity and
      mortality associated with chronic obstructive pulmonary disease (COPD). Some
      patients suffer an inordinate number of exacerbations while others remain
      relatively protected. The aim of this study was to evaluate the potentially
      modifiable precipitating parameters of frequent severe exacerbations requiring
      hospital admission in COPD. MATERIALS AND METHODS: Consecutive patients admitted
      with acute exacerbation of COPD for a period of one year in a tertiary care
      hospital were evaluated prospectively. Data regarding the number of exacerbations
      in the previous year, current comorbidities, medications, and clinical and
      functional status of COPD patients were evaluated. RESULTS: We included 98 COPD
      patients (81.63% men) admitted consecutively with exacerbations in our
      department. The mean number of severe exacerbations was (2.42 per patient/per
      year), and 65% of the patients had frequent severe exacerbations. Multivariate
      analysis indicated that serum uric acid, serum total IgE, depression and anxiety,
      gastroesophageal reflux disease symptoms, air pollution, poor adherence to
      inhaled therapy, and irregular outpatient followup visits were independent
      predictors of frequent severe exacerbations. CONCLUSION: COPD patients with
      frequent exacerbations should be carefully assessed for modifiable confounding
      risk factors regardless of poor lung function to decrease exacerbation frequency
      and related poor prognosis. Raised serum total IgE levels may point towards atopy
      as an additional comorbidity in COPD while uric acid can have a clinically useful
      role in risk stratification in a primary care setting.

PMID- 27890986
TI  - Correlation of chest computed tomography findings with dyspnea and lung functions
      in post-tubercular sequelae.
AB  - AIMS: To study the correlation between dyspnea, radiological findings, and
      pulmonary function tests (PFTs) in patients with sequelae of pulmonary
      tuberculosis (TB). MATERIALS AND METHODS: Clinical history, chest computed
      tomography (CT), and PFT of patients with post-TB sequelae were recorded. Dyspnea
      was graded according to the Modified Medical Research Council (mMRC) scale. CT
      scans were analyzed for fibrosis, cavitation, bronchiectasis, consolidation,
      nodules, and aspergilloma. Semi-quantitative analysis was done for these
      abnormalities. Scores were added to obtain a total morphological score (TMS). The
      lungs were also divided into three zones and scores added to obtain the total
      lung score (TLS). Spirometry was done for forced vital capacity (FVC), forced
      expiratory volume in 1 s (FEV1), and FEV1/FVC. RESULTS: Dyspnea was present in
      58/101 patients. A total of 22/58 patients had mMRC Grade 1, and 17/58 patients
      had Grades 2 and 3 dyspnea each. There was a significant difference in median
      fibrosis, bronchiectasis, nodules (P < 0.01) scores, TMS, and TLS (P < 0.0001)
      between dyspnea and nondyspnea groups. Significant correlations were obtained
      between grades of dyspnea and fibrosis (r = 0.34, P = 0.006), bronchiectasis (r =
      0.35, P = 0.004), nodule (r = 0.24, P = 0.016) scores, TMS (r = 0.398, P =
      0.000), and TLS (r = 0.35, P = 0.0003). PFTs were impaired in 78/101 (77.2%)
      patients. Restrictive defect was most common in 39.6% followed by mixed in 34.7%.
      There was a negative but statistically insignificant trend between PFT and
      fibrosis, bronchiectasis, nodule scores, TMS, and TLS. However, there were
      significant differences in median fibrosis, cavitation, and bronchiectasis scores
      in patients with normal, mild to moderate, and severe respiratory defects. No
      difference was seen in TMS and TLS according to the severity of the respiratory
      defect. CONCLUSION: Both fibrosis and bronchiectasis correlated with dyspnea and
      with PFT. However, this correlation was not linear. The overall extent of
      radiological abnormalities correlated only with dyspnea but not with PFT.

PMID- 27890988
TI  - Variability in proteinase-antiproteinase balance, nutritional status, and quality
      of life in stable chronic obstructive pulmonary disease due to tobacco and
      nontobacco etiology.
AB  - CONTEXT: Although the role of proteinase/antiproteinase imbalance in chronic
      obstructive pulmonary disease (COPD) due to tobacco is well established,
      information in COPD due to nontobacco etiology is sparse. AIMS: To assess the
      variability in metalloproteinase activity in COPD related to tobacco and
      nontobacco causes. SETTINGS AND DESIGN: This is a hospital-based, prospective,
      observational study. SUBJECTS AND METHODS: Serum matrix metalloproteinase-9 (MMP
      9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were estimated in 200
      subjects divided equally into four groups, i.e. COPD in tobacco smokers, COPD in
      nonsmokers but with exposure to biomass-related indoor air pollution, smokers
      without COPD, and nonsmoking healthy controls. Anthropometric skinfold
      measurements, quality of life (QOL) using St. George Respiratory Questionnaire,
      and exercise capacity using the 6-min walk test (6-MWT) were carried out. Groups
      were compared using analysis of variance and Kruskal-Wallis plus Mann-Whitney U
      test to assess differences between groups. The Chi-square and Fisher's exact
      tests were used to evaluate associations among categorical variables. Spearman's
      rank correlation was calculated to assess the correlation between data. RESULTS:
      Patients with COPD due to either tobacco or nontobacco etiology were older, more
      malnourished, had worse QOL, and poorer exercise capacity compared to non-COPD
      subjects. Triceps, subscapular, and suprailiac skinfold thicknesses were less in
      smokers with COPD than biomass-related COPD. MMP-9 and TIMP-1 levels were similar
      across all groups. TIMP-1 significantly correlated with 6-MWT among all groups.
      CONCLUSIONS: The protease-antiprotease balance in COPD is similar irrespective of
      the presence or absence of tobacco exposure but is related to poor exercise
      capacity.

PMID- 27890989
TI  - The burden of segregated respiratory diseases in India and the quality of care in
      these patients: Results from the Asia-Pacific Burden of Respiratory Diseases
      study.
AB  - BACKGROUND: Chronic respiratory diseases such as asthma, allergic rhinitis (AR),
      chronic obstructive pulmonary disease (COPD), and rhinosinusitis are becoming
      increasingly prevalent in the Asia-Pacific region. The Asia-Pacific Burden of
      Respiratory Diseases study examined the disease and economic burden of AR,
      asthma, COPD, and rhinosinusitis across the Asia-Pacific and more specifically
      India. OBJECTIVES: To estimate the proportion of adults receiving care for
      asthma, AR, COPD, and rhinosinusitis and assess the economic burden, both direct
      and indirect of these chronic respiratory disease. SUBJECTS AND METHODS:
      Consecutive participants aged >=18 years with a primary diagnosis of asthma, AR,
      COPD, or rhinosinusitis were enrolled. Surveys comprising questions about
      respiratory disease symptoms, healthcare resource utilization, work productivity,
      and activity impairment were completed by treating physicians and participants
      during one study visit. Costs, indirect and direct, that contributed to treatment
      for each of the four respiratory diseases were calculated. RESULTS: A total of
      1000 patients were enrolled. Asthma was the most frequent primary diagnosis
      followed by AR, COPD, and rhinosinusitis. A total of 335 (33.5%) patients were
      diagnosed with combinations of the four respiratory diseases; the most frequently
      diagnosed combinations were asthma/AR and rhinosinusitis/AR. Cough or coughing up
      sputum was the primary reason for the current visit by patients diagnosed with
      asthma and COPD while AR patients reported a watery, runny nose, and sneezing;
      patients with rhinosinusitis primarily reported a colored nasal discharge. The
      mean annual cost per patient was US$637 (SD 806). The most significant driver of
      direct costs was medications. The biggest cost component was productivity loss.
      CONCLUSIONS: Given the ongoing rapid urbanization of India, the frequency of
      respiratory diseases and their economic burden will continue to rise. Efforts are
      required to better understand the impact and devise strategies to appropriately
      allocate resources.

PMID- 27890990
TI  - Percutaneous computed tomography-guided aspiration and biopsy of intrathoracic
      lesions: Results of 265 procedures.
AB  - CONTEXT: Percutaneous computed tomography (CT)-guided needle aspiration and
      biopsy technique have developed over time as a method for obtaining tissue
      specimen. Although this is a minimally invasive procedure, complications do
      occasionally occur. AIMS: The aim of the study was to evaluate the diagnostic
      yield and complications of 265 percutaneous CT-guided aspiration and biopsy
      procedures performed on various intrathoracic lesions. SETTINGS AND DESIGN: Data
      of percutaneous CT-guided aspiration and biopsy procedures of intrathoracic
      lesions performed over a 4 year period were retrospectively analyzed. SUBJECTS
      AND METHODS: Procedure details, radiological images, and pathological and
      microbiological reports were retrieved from radiology records and hospital
      information system. Technical success, diagnostic yield, and complication rates
      were calculated. RESULTS: Total 265 procedures were performed for lung (n = 179),
      mediastinum (n = 73), and pleural lesions (n = 13). Diagnostic yield for lung,
      mediastinal, and pleural lesions was 80.7%, 74.2, and 75%, respectively, for core
      biopsy specimens. Major complication was noted in only one procedure (0.4%).
      Minor complications were noted in 13.6% procedures which could be managed
      conservatively. CONCLUSIONS: Percutaneous CT-guided aspiration and biopsy
      procedures for intrathoracic lesions are reasonably safe with good diagnostic
      yield. Complications are infrequent and conservatively managed in most of the
      cases.

PMID- 27890992
TI  - Lung malignancy: Diagnostic accuracies of bronchoalveolar lavage, bronchial
      brushing, and fine needle aspiration cytology.
AB  - BACKGROUND: Early diagnosis of lung cancer plays a pivotal role in reducing lung
      cancer death rate. Cytological techniques are safer, economical and provide quick
      results. Bronchoscopic washing, brushing and fine needle aspirations not only
      complement tissue biopsies in the diagnosis of lung cancer but also comparable.
      OBJECTIVES: (1) To find out diagnostic yields of bronchioalveolar lavage,
      bronchial brushings, FNAC in diagnosis of lung malignancy. (2) To compare
      relative accuracy of these three cytological techniques. (3) To correlate the
      cytologic diagnosis with clinical, bronchoscopic and CT findings. (4) Cytological
      and histopathological correlation of lung lesions. METHODS: All the patients who
      came with clinical or radiological suspicion of lung malignancy in two and a half
      year period were included in study. Bronchoalveolar lavage was the most common
      type of cytological specimen (82.36%), followed by CT guided FNAC (9.45%) and
      bronchial brushings (8.19%). Sensitivity, specificity, positive and negative
      predictive value for all techniques and correlation with histopathology was done
      using standard formulas. RESULTS: The most sensitive technique was CT FNAC -
      (87.25%) followed by brushings (77.78%) and BAL (72.69%). CT FNAC had highest
      diagnostic yield (90.38%), followed by brushings (86.67%) and BAL (83.67%).
      Specificity and positive predictive value were 100 % each of all techniques.
      Lowest false negatives were obtained in CT FNAC (12.5%) and highest in BAL
      (27.3%). Highest negative predictive value was of BAL 76.95 % followed by BB
      75.59% and CT FNAC 70.59%. CONCLUSION: Before administering antitubercular
      treatment every effort should be made to rule out malignancy. CT FNAC had highest
      diagnostic yield among three cytological techniques. BAL is an important tool in
      screening central as well as in accessible lesions. It can be used at places
      where CT guided FNAC is not available or could not be done due to technical or
      financial limitations.

PMID- 27890991
TI  - Pulmonary alveolar proteinosis: Experience from a tertiary care center and
      systematic review of Indian literature.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized
      by deposition of lipoproteinaceous material within alveoli, with a variable
      clinical course. Here, we report an experience of management of PAP at our
      center. A systematic review of previously reported cases from India is also
      included in the article. MATERIALS AND METHODS: This study included patients with
      primary PAP managed at our center from 2009 to 2015. Diagnosis of primary PAP was
      based on histopathologic diagnosis on bronchoalveolar lavage or transbronchial
      lung biopsy and absence of causes of secondary PAP. For systematic review of
      Indian publications, the literature search was performed using PubMed and EMBASE
      databases using the terms "pulmonary alveolar proteinosis'" or "alveolar
      proteinosis" and "India" or "Indian." RESULTS: During the above-specified period,
      five patients with diagnosis of PAP were admitted at our center. Median age of
      patients was 32 years (interquartile range [IQR] 30.5-59); 80% were female. Mean
      duration (+/- standard deviation) of symptoms was 6.2 (+/-1.79) months. Anti
      granulocyte-macrophage colony stimulating factor (GM-CSF) antibodies were
      elevated in 4 out of 5 patients (80%). For management, whole lung lavage (WLL)
      was done for four patients with median volume of 32.5 (IQR 18-74) L per patient.
      All the patients showed significant symptomatic as well as improvement in
      physiological parameters. Subcutaneous GM-CSF and ambroxol were given to 3
      patients and 1 patient, respectively. The median follow-up of all patients was 18
      (IQR 5-44) months. A systematic review of all Indian studies of PAP revealed
      thirty publications. CONCLUSIONS: WLL is the most common, effective, and safe
      therapy in patients with PAP. GM-CSF administration is an efficacious treatment
      for patients with incomplete response after WLL.

PMID- 27890993
TI  - Ankylosing spondylitis and risk of venous thromboembolism: A systematic review
      and meta-analysis.
AB  - BACKGROUND: Several immune-mediated inflammatory disorders, such as rheumatoid
      arthritis, psoriatic arthritis, and systemic lupus erythematosus have been linked
      to an increased risk of venous thromboembolism (VTE). However, the data on
      ankylosing spondylitis (AS) are limited. METHODS: We conducted a systematic
      review and meta-analysis of observational studies that reported odds ratio,
      relative risk, hazard ratio, or standardized incidence ratio comparing the risk
      of VTE and possible pulmonary embolism (PE) in patients with AS versus non-AS
      participants. Pooled risk ratio and 95% confidence intervals were calculated
      using a random-effect, generic inverse variance method of DerSimonian and Laird.
      RESULTS: Of 423 potentially relevant articles, three studies met our inclusion
      criteria and thus, were included in the data analysis. The pooled risk ratio of
      VTE in patients with AS was 1.60 (95% confidence interval: 1.05-2.44). The
      statistical heterogeneity of this study was high with an I2 of 93%. CONCLUSION:
      Our study demonstrated a statistically significant increased VTE risk among
      patients with AS.

PMID- 27890994
TI  - Quantitative computed tomography imaging in chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease having
      small airway inflammation, emphysema, and pulmonary hypertension. It is now clear
      that spirometry alone cannot differentiate each component. Quantitative computed
      tomography (QCT) is increasingly used to quantify the amount of emphysema and
      small airway involvement in COPD. Inspiratory CT guides in assessing emphysema
      while expiratory CT identifies areas of air trapping which is a surrogate of
      small airway inflammation. By constructing a three-dimensional model of airways,
      we can also measure the airway wall thickness of segmental and subsegmental
      airways. The aim of this review is to present the current knowledge and
      methodologies in QCT of the lung that aid in identifying discrete COPD
      phenotypes.

PMID- 27890995
TI  - Endotracheobronchial lymphoma: Two unusual case reports and review of article.
AB  - The tracheobronchial origin of non-Hodgkin's lymphoma (NHL) is a very rare
      presentation, and there are only a few case reports of primary tracheal or
      endobronchial NHL. We have two cases of primary tracheobronchial NHL; one case
      was incidentally diagnosed as anaplastic large cell lymphoma of endobronchial
      origin when a comprehensive workup and surgery were carried out for an
      endobronchial aspergilloma which was actually sitting on top of lymphoma. The
      second patient was a case of myelodysplastic syndrome who presented with acute
      respiratory distress; on thorough workup, he was found to have endotracheal B
      cell lymphoma. Both cases were responding well with standard chemotherapy. The
      mortality in these kinds of patients is due to disease progression or airway
      compromise and treatment complications.

PMID- 27890996
TI  - Dry cough in a middle-aged man.
AB  - Cough is often a distressing feature and may be caused due to varied reasons. A
      39-year-old man presented with complaints of cough and had significant pigeon
      exposure. His chest X-ray revealed mediastinal enlargement and computed
      tomography chest revealed air trapping and mediastinal lymphadenopathy. Both
      endobronchial and transbronchial biopsies revealed granulomas. Thus, the patient
      was diagnosed as a case of sarcoidosis and started on steroids. Hypersensitivity
      pneumonitis may often mimic sarcoidosis; however, the presence of endobronchial
      granulomas will diagnose the latter condition.

PMID- 27890998
TI  - Foreign body in the lung following dental procedure.
AB  - This is an interesting case report of a foreign body (FB) aspiration in an adult
      patient. The FB in question was a dental drill, which accidentally went into the
      airways during a dental procedure. The extraction was technically difficult due
      to the peripheral location and thin and sharp tip of the FB. The extraction of
      this FB required a unique innovation through the rigid bronchoscope.

PMID- 27890997
TI  - Complete subglottic tracheal stenosis managed with rigid bronchoscopy and T-tube
      placement.
AB  - Surgery is the preferred treatment modality for benign tracheal stenosis.
      Interventional bronchoscopy is used as a bridge to surgery or in instances when
      surgery is not feasible or has failed. Stenosis in the subglottic trachea is
      particularly a treatment challenge, in view of its proximity to the vocal cords.
      Herein, we describe a patient with complete tracheal stenosis in the subglottic
      region, which developed after prolonged intubation and mechanical ventilation.
      The patient developed recurrent stenosis despite multiple surgical and endoscopic
      procedures. We were able to manage the patient successfully with rigid
      bronchoscopy and Montgomery T-tube placement.

PMID- 27890999
TI  - Lophomonas blattarum infection in immunocompetent patient.
AB  - Lophomonas blattarum (L. blattarum) is a protozoan parasite living in intestinal
      tracts of termites and cockroaches. Chen and Meng from China repoted first case
      of pulmonary L. blattarum infection in 1993. 137 cases have only been reported in
      literature between 1993 to 2013. Majority of these infections occur in
      immunocompromised patients and have been reported from China. We report a case of
      this rare entity in an immunocompetent young Indian male.

PMID- 27891000
TI  - An unusual metastasis of lung adenocarcinoma: Biceps brachii muscle.
AB  - Skeletal muscle metastasis of nonsmall cell lung carcinoma (NSCLC) is a rare
      occurrence, and the most effective treatment modality is currently unknown. In
      this case presentation, we report a patient with NSCLC who underwent palliative
      radiotherapy for biceps muscle metastasis of NSLCS. Our case was a 49-year-old
      woman who had lung adenocarcinoma with biceps muscle metastasis. She had been
      followed up for 2 years due to Stage IV lung adenocarcinoma from whom a biopsy
      was taken from a painful mass in right arm that was found to be compatible with
      metastasis of lung adenocarcinoma. She had palliative radiotherapy for her
      painful mass and systemic chemotherapy was planned. After palliative
      radiotherapy, the pain originating from the metastatic mass in right biceps
      muscle alleviated. Palliative radiotherapy can be a valuable treatment option for
      cases with skeletal muscle metastasis.

PMID- 27891001
TI  - Rigid bronchoscopic management of acute respiratory failure in a 30-year-old
      woman.
AB  - A 30-year-old woman presented with a history of progressive shortness of breath,
      cough, and hoarseness. Stridor was audible on examination. Chest X-ray showed
      normal lung fields and contrast-enhanced computed tomography thorax showed lower
      tracheal occlusion with endoluminal growth. Diagnostic flexible bronchoscopy
      demonstrated multiple whitish glistening nodules over both vocal cords and lower
      tracheal occlusion by whitish nodular growth. In view of critical central airway
      obstruction, rigid bronchoscopy and excision of the lower tracheal growth were
      performed. Histopathological examination of the excised specimen demonstrated
      features of squamous papillomas. A diagnosis of respiratory papillomatosis was
      established. On follow-up surveillance bronchoscopy, there was a gradual
      spontaneous regression of the residual lesions, and the patient remains currently
      asymptomatic 1 year since the procedure.

PMID- 27891002
TI  - Idiopathic dilatation of pulmonary artery.
AB  - Idiopathic dilatation of pulmonary arteries (IDPA) is a rare abnormality of
      pulmonary arteries, the reported incidence in literature being as low as 0.007%
      in autopsy samples. With the improvement in diagnostic modalities, antemortem
      diagnosis of IDPA has been increasingly established by excluding diseases that
      induce pulmonary arterial enlargement. Here, we present a rare case of idiopathic
      dilatation of the pulmonary artery admitted with shortness of breath where IDPA
      was diagnosed as an incidental finding using computed tomography pulmonary
      angiography and cardiac catheterization.

PMID- 27891003
TI  - Obese COPD is associated with higher systemic inflammation - A new COPD
      phenotype.

PMID- 27891004
TI  - Abnormal central line position on a chest radiograph: Clue to an uncommon
      anomaly.

PMID- 27891006
TI  - Rare cause of spontaneous subcutaneous emphysema.

PMID- 27891005
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration of thyroid:
      Report of two cases and systematic review of literature.
AB  - Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a
      minimally invasive and safe technique for a sampling of mediastinal lesions.
      Indications for EBUS-TBNA have gradually expanded since its introduction. The
      usual approach to cytological sampling of the thyroid gland is percutaneous
      ultrasound-guided fine needle aspiration (US-FNA) performed under local
      anesthesia. US-FNA may be risky or not feasible in intrathoracic/substernal
      thyroid location. Feasibility of aspirating thyroid lesions with EBUS-TBNA has
      been occasionally reported. We report two patients wherein EBUS-TBNA was utilized
      for thyroid lesion aspiration and definitive diagnosis. We highlight the utility
      and safety of EBUS-TBNA in the evaluation of intrathoracic thyroid lesions
      wherein image-guided percutaneous aspiration may be risky/sometimes impossible to
      perform. A systematic review of literature has also been performed summarizing
      and discussing the issues pertaining to EBUS-TBNA of the thyroid gland.

PMID- 27891007
TI  - Multicentric Castleman's disease: "A rare entity that mimics malignancy".

PMID- 27891008
TI  - Pulmonary strongyloidiasis and hyperinfection in a renal transplant patient.

PMID- 27891009
TI  - A forgotten foreign body in bronchus.

PMID- 27891010
TI  - Chronic obstructive pulmonary disease and cardiac comorbidities: A cross
      sectional study.

PMID- 27891011
TI  - Excessive dynamic airway collapse and wheeze: Reasons for contemplation.

PMID- 27891012
TI  - Pleural nodules: A rare presentation of extrapulmonary tuberculosis.

PMID- 27891013
TI  - A rare cause of lung cavity.

PMID- 27891014
TI  - Chronic granulomatous disease may be an underlying cause for invasive
      nocardiosis.

PMID- 27891015
TI  - Erratum: Enhancing indoor air quality: The air filter advantage.
AB  - [This corrects the article on p. 473 in vol. 32, PMID: 26628762.].

PMID- 27891016
TI  - Special issue on medicolegal issues in neurology.

PMID- 27891017
TI  - Foreword.

PMID- 27891018
TI  - Legal challenges in neurological practice.
AB  - Clinical neuroscience has made tremendous advances over the last century.
      Neurology as a discipline is still considered challenging and at times risky due
      to the natural history and progressive course of few of the neurological
      diseases. Encouragingly, the patient and their caregivers are now increasingly
      willing to be actively involved in making decisions. The patients' relationship
      with the doctor is a reflection of the society. A society that is orienting
      itself toward "rating" and "feedback" has made this doctor-patient relationship,
      a consumer-service provider relationship. This perhaps is due to
      commercialization of health that usually accompanies globalization. Moreover, a
      rapid influx of information from potential erroneous sources such as the Internet
      has also made patient and caregivers not being hesitant to taking legal course in
      the case of adverse events during treatment or simply because of dissatisfaction.
      The purpose of the legal process initiated by patients with neurological ailments
      is more often to compensate for the income lost, physical and psychological
      anguish that accompanies disease and its treatment, and to fund treatment or
      rehabilitation requirements. However, it is not clearly established if monetary
      benefits acquired lead to better opportunities for recovery of the patient. The
      consumer protection act and commercialization of medical services may well have
      an adverse effect on the doctor and patient relationship. Hence, there is a great
      need for all medical professionals to mutually complement and update each other.
      This review examines legal (litigation) processes with special interest on
      medicolegal system in patients with neurological ailments and the challenges
      faced by the neurologist during day-to-day clinical practice.

PMID- 27891019
TI  - Medical negligence: Indian legal perspective.
AB  - A basic knowledge of how judicial forums deal with the cases relating to medical
      negligence is of absolute necessity for doctors. The need for such knowledge is
      more now than before in light of higher premium being placed by the Indian forums
      on the value of human life and suffering, and perhaps rightly so. Judicial
      forums, while seeking to identify delinquents and delinquency in the cases of
      medical negligence, actually aim at striking a careful balance between the
      autonomy of a doctor to make judgments and the rights of a patient to be dealt
      with fairly. In the process of adjudication, the judicial forums tend to give
      sufficient leeway to doctors and expressly recognize the complexity of the human
      body, inexactness of medical science, the inherent subjectivity of the process,
      genuine scope for error of judgment, and the importance of the autonomy of the
      doctors. The law does not prescribe the limits of high standards that can be
      adopted but only the minimum standard below which the patients cannot be dealt
      with. Judicial forums have also signaled an increased need of the doctors to
      engage with the patients during treatment, especially when the line of treatment
      is contested, has serious side effects and alternative treatments exist.

PMID- 27891020
TI  - Preventing medico-legal issues in clinical practice.
AB  - The medical profession is considered to be one of the noblest professions in the
      world. The practice of medicine is capable of rendering noble service to humanity
      provided due care, sincerity, efficiency, and professional skill is observed by
      the doctors. However, today, the patient-doctor relationship has almost
      diminished its fiduciary character and has become more formal and structured.
      Doctors are no longer regarded as infallible and beyond questioning.
      Corporatization of health care has made it like any other business, and the
      medical profession is increasingly being guided by the profit motive rather than
      that of service. On the other hand, a well-publicized malpractice case can ruin
      the doctor's career and practice. The law, like medicine, is an inexact science.
      One cannot predict with certainty an outcome of cases many a time. It depends on
      the particular facts and circumstances of the case, and also the personal notions
      of the judge concerned who is hearing the case. The axiom "you learn from your
      mistakes" is too little honored in healthcare. The best way to handle medico
      legal issues is by preventing them, and this article tries to enumerate the
      preventive measures in safeguarding the doctor against negligence suit.

PMID- 27891021
TI  - Progress in Medicine: Compensation and medical negligence in India: Does the
      system need a quick fix or an overhaul?
AB  - In a recent judgment on medical negligence, the Supreme Court awarded
      compensation amounting to Rs. 11 crore to a victim, which was to be paid by the
      doctors and the private hospital deemed responsible for the wrongful death of a
      patient. This landmark decision was by far the largest compensation award in the
      history of Indian medical negligence litigation. Hence, the process of
      calculating compensation for medical negligence has received great attention and
      debate, largely due to the impact that it is going to have on the practice of
      medicine within the country, in the near future. However, the method of
      calculation of compensation is unpredictable as it varies hugely across different
      cases, courts and tribunals resulting, in a loss of faith in the system,
      protracted litigation, and frequent appeals. With over 80% of India's healthcare
      being provided by the private sector, predictability and uniformity in the
      regulation of compensation in medical negligence would benefit the victims and
      the doctors concerned. A basic knowledge of how medical negligence compensation
      is calculated and adjudicated in the judicial courts of India will aid a doctor
      in planning his/her professional indemnity insurance, as well as in practicing
      his/her profession without undue worry about facing litigation for alleged
      medical negligence. This article addresses the merits and demerits of large
      compensation awards, and also discusses whether the system is broken, needs a
      quick fix, or a massive overhaul.

PMID- 27891022
TI  - The rights of persons with disability bill, 2014: Implications for neurological
      disability.
AB  - India ratified the United Nations Convention on the Rights of Persons with
      Disabilities (UNCRPD) in 2007. This is a welcome step toward realizing the rights
      of the persons with disability. The UNCRPD proclaims that disability results from
      interaction of impairments with attitudinal and environmental barriers, which
      hinders full and active participation in society on an equal basis with others.
      Further, the convention also mandates the signatory governments to make suitable
      changes in the existing laws of the country, to identify and eliminate obstacles
      and barriers, and to comply with the terms of the UNCRPD in order to protect the
      rights of the person with disabilities, hence the amendments of the national
      laws. Hence, the Government of India drafted the Right of Persons with
      Disabilities Bill (RPWD Bill), 2014. It is evident that neurological disorders
      are emerging as priority health problems worldwide. They not only contribute to
      mortality but also contribute to huge morbidity. Further, shortage of
      neurologists, huge treatment gap, and stigma add to the burden. The situation
      becomes worse with regard to providing quality care, comprehensive
      rehabilitation, and social welfare measures to persons with neurological
      disability. There is no doubt that persons with neurological disability do not
      get adequate representation, stigmatized and discriminated across the civil
      societies, which hinders full and active participation in society. Hence, this
      article is a critique of the RPWD Bill, 2014 from the perspective of persons with
      neurological and neurosurgical disability. Further, this article also discusses
      challenges in quantifying and certifying disability in neurological disability.

PMID- 27891024
TI  - Palliative care and the Indian neurologist.
AB  - End-of-life care is an integral part of neurology practice, and neuropalliative
      medicine is an emerging neurology subspeciality. This begins with serious illness
      communication as a protocol-based process that depends on an evaluation of
      patient autonomy and accurate prognostication. Communication needs vary between
      chronic, life-limiting neurologic illnesses and acute brain injury. In an ideal
      situation, the patient's wishes are spelled out in advance care plans and living
      wills, and surrogates have only limited choices for implementation. Palliative
      care prepares for decline and death as an expected outcome and focuses on
      improving the quality of life for both the patients and their caregivers. In the
      Intensive Care Unit, this may require clarity on withholding and withdrawal of
      treatment. In all locations of care, the emphasis is on symptom control.
      Neurologists are the quintessential physicians, and our "dharma" is best served
      by empathetically bringing our technical knowledge and communication skills into
      easing this final transition for our patients and their families to the best of
      our ability.

PMID- 27891023
TI  - Capacity issues and decision-making in dementia.
AB  - Capacity to make one's own decisions is fundamental to the autonomy of the
      individual. Capacity is a functional assessment made by a clinician to determine
      if a patient is capable of making a specific decision. Competency is a global
      assessment and legal determination made by a judge in court. Capacity evaluation
      for a patient with dementia is used to determine whether the patient is capable
      of giving informed consent, participate in research, manage their finances, live
      independently, make a will, and have ability to drive. Patients with dementia
      cannot be assumed to have impaired capacity. Even a patient with moderate or
      severe dementia, with obviously impaired capacity may still be able to indicate a
      choice and show some understanding. Four key components of decision-making in a
      capacity evaluation include understanding, communicating a choice, appreciation,
      and reasoning. Assessment of capacity requires a direct interview with the
      patient using open-ended questions and may include both informal and formal
      approaches depending on the situation and the context. A baseline cognitive
      evaluation with a simple test to assess executive function is often useful in
      capacity evaluation. All capacity evaluations are situation specific, relating to
      the particular decision under consideration, and are not global in scope. The
      clinician needs to spend adequate time with the patient and the family allaying
      their anxieties and also consider the sociocultural context. The area of capacity
      has considerable overlap with law and the clinician treating patients with
      dementia should understand the complexities of assessment and the implications of
      impaired capacity. It is also essential that the clinician be well informed and
      keep meticulous records. It is crucial to strike a balance between respecting the
      patient autonomy and acting in his/her best interest.

PMID- 27891025
TI  - External syrinx-introduction of a new term.

PMID- 27891026
TI  - Anaesthesia management in craniovertebral junctional anomalies.
AB  - Craniovertebral Junctional (CVJ) anomalies are developmental disorders that
      affect the skeleton and enclosed neuraxis at the junction of cranium and cervical
      spine. The high prevalence of airway obstruction and restrictive pulmonary
      disease in combination with cardiovascular manifestations poses a high
      anaesthetic risk to these patients. This article provides a discussion of
      management of anaesthesia in patients with craniovertebral anomalies, the
      evaluation of risk factors in these patients and their management, including
      emergency airway issues.

PMID- 27891028
TI  - Is the existence of cervical rib an advantage for C7 posterior stabilization?
AB  - BACKGROUND AND AIM: Defining a new screwing method for C7 posterior stabilization
      in case of a cervical rib existence aimed in this report. MATERIALS AND METHODS:
      Ten adult patients, five of which without cervical rib (Group 1) and the other
      five of which (Group 2) with cervical rib that has been chosen from the radiology
      archive. Axial, sagittal, coronal sections of cervical computed tomography and
      three-dimensional images were obtained. Lateral mass sizes of all cases were
      measured and compared between two groups. The relationship between cervical rib
      and lateral mass was identified in Group 2. RESULTS: The mean length, width, and
      height of lateral masses were measured respectively, as 5.4, 17.6, and 12.7 mm in
      Group 1. The measurement of Group 2 (with cervical rib) revealed the mean length
      of 20.7, the width of 20.4, and the height of 15.9 mm. When both groups were
      compared, there were no significant differences between the width and height of
      the lateral masses. However, axial measurements of Group 2 revealed a remarkable
      and significant length for screwing. CONCLUSION: In patients with cervical rib,
      directing lateral mass screw toward cervical rib conjoint can present a simple
      and reliable alternative method in C7 posterior stabilization process.

PMID- 27891027
TI  - Purely extradural spinal nerve root hemangioblastomas.
AB  - Spinal nerve root hemangioblastomas present mostly as intradural-extradurally.
      Purely extradural spinal nerve root hemangioblastoma is a very rare entity. In
      this study, we aimed to analyze epidemiological perspectives of purely extradural
      spinal nerve root hemangioblastomas presented in English medical literature in
      addition to our own exemplary case. PubMed/MEDLINE was searched using the terms
      "hemangioblastoma," "extradural," "spinal," and "nerve root." Demographical
      variables of age, gender, concomitant presence of von Hippel-Lindau (VHL)
      disease; spinal imaging and/or intraoperative findings for tumor location were
      surveyed from retrieved articles. There are 38 patients with purely extradural
      spinal nerve root hemangioblastoma. The median age is 45 years (range = 24-72
      years). Female:male ratio is 0.6. Spinal levels for purely extradural spinal
      nerve root hemangioblastomas, in order of decreasing frequency, are thoracic
      (48.6%), cervical (13.5%), lumbar (13.5%), lumbosacral (10.8%), sacral (8.1%),
      and thoracolumbar (5.4%). Concomitant presence of VHL disease is 45%. Purely
      extradural spinal nerve root hemangioblastomas are very rare and can be confused
      with other more common extradural spinal cord tumors. Concomitant presence of VHL
      disease is observed in less than half of the patients with purely extradural
      spinal nerve root hemangioblastomas. Surgery is the first-line treatment in these
      tumors.

PMID- 27891029
TI  - Craniovertebral junction 360 degrees : A combined microscopic and endoscopic
      anatomical study.
AB  - OBJECTIVES: Craniovertebral junction (CVJ) can be approached from various
      corridors depending on the location and extent of disease. A three-dimensional
      understanding of anatomy of CVJ is paramount for safe surgery in this region. Aim
      of this cadaveric study is to elucidate combined microscopic and endoscopic
      anatomy of critical neurovascular structures in this area in relation to bony and
      muscular landmarks. MATERIALS AND METHODS: Eight fresh-frozen cadaveric heads
      injected with color silicon were used for this study. A stepwise dissection was
      done from anterior, posterior, and lateral sides with reference to bony and
      muscular landmarks. Anterior approach was done endonasal endoscopically.
      Posterior and lateral approaches were done with a microscope. In two specimens,
      both anterior and posterior approaches were done to delineate the course of
      vertebral artery and lower cranial nerves from ventral and dorsal aspects.
      RESULTS: CVJ can be accessed through three corridors, namely, anterior,
      posterior, and lateral. Access to clivus, foreman magnum, occipital cervical
      joint, odontoid, and atlantoaxial joint was studied anteriorly with an endoscope.
      Superior and inferior clival lines, supracondylar groove, hypoglossal canal, arch
      of atlas and body of axis, and occipitocervical joint act as useful bony
      landmarks whereas longus capitis and rectus capitis anterior are related muscles
      to this approach. In posterior approach, spinous process of axis, arch of atlas,
      C2 ganglion, and transverse process of atlas and axis are bony landmarks. Rectus
      capitis posterior major, superior oblique, inferior oblique, and rectus capitis
      lateralis (RCLa) are muscles related to this approach. Occipital condyles,
      transverse process of atlas, and jugular tubercle are main bony landmarks in
      lateral corridor whereas RCLa and posterior belly of digastric muscle are the
      main muscular landmarks. CONCLUSION: With advances in endoscopic and microscopic
      techniques, access to lesions and bony anomalies around CVJ is becoming easier
      and straightforward. A combination of microscopic and endoscopic techniques is
      more useful to understand this anatomy and may aid in the development of future
      combined approaches.

PMID- 27891031
TI  - Spinal compression fractures due to pregnancy-associated osteoporosis.
AB  - OBJECTIVES: To report on unique cases of spinal compression fractures due to
      pregnancy-associated osteoporosis (PAO) and to suggest a satisfactory treatment
      modality. MATERIALS AND METHODS: A single-center retrospective study. We reviewed
      the data of 535 patients with osteoporotic spinal compression fractures over a
      period of 5-year. Two patients who developed spinal compression fractures due to
      PAO were identified and treated. RESULTS: The clinical presentation and blood
      investigations ruled out other causes of osteoporosis. Dual-energy X-ray
      absorptiometry was used to confirm the diagnosis. All patients improved with
      medical management. CONCLUSION: Vertebral fractures due to PAO should be
      considered as a differential diagnosis in patients with back pain who are in the
      third trimester of pregnancy or in postpartum. Early recognition and appropriate
      conservative management would be necessary to prevent complications such as new
      vertebral fractures and chronic back pain.

PMID- 27891030
TI  - The role of transforaminal percutaneous endoscopic discectomy in lumbar disc
      herniations.
AB  - OBJECTIVES: To study 1)the efficacy of transforaminal percutaneous endoscopic
      lumbar discectomy in lumbar disc herniations.2) limitations and advantages of the
      surgical procedure. 3)morbidity and complications associated with the procedure.
      MATERIALS AND METHODS: This study was carried out on 120 patients who had single
      level herniated disc Pre-operative assessment of VAS and MSS scoring systems were
      documented one day prior to surgery. Post operative results were determined by
      MacNab criteria and by modified Suezawa and Schreiber clinical scoring system
      (MSS score). RESULTS: Maximum patients were in the age group of 31 to 40 years
      and 83.43% of the patients were males. 80% patients had lumbar disc herniation at
      L4-L5 level, The mean operative time of endoscopic discectomy was 52.28 minutes
      and the mean hospital stay was 2.1days.8 cases of L5-S I were abandoned due to
      high iliac bone and hence their disc could not be accessed. Out of 112 patients
      who underwent operation, 2 patients developed discitis and 1 was found to have
      dysesthesia. Also recurrent prolapsed intervertebral disc was seen in 6 cases The
      mean preoperative and 6 months follow-up VAS score was 8.4 and 1.89 respectively.
      Mean preoperative and 6 months follow-up Modified Suezawa And Schreiber Clinical
      Scoring System(MSS Score) was 3.47 and 7.92 respectively. MSS score showed
      excellent and good outcome in 82.12% patients and Modified Macnab Criteria showed
      excellent and good outcome in 89.3% patients at 6months follow-up. CONCLUSION:
      TPELD can be a reasonable alternative to conventional microscopic discectomy for
      the treatment of patients with LDH. We also conclude that TPELD is not an
      effective procedure for L5-S 1 disc and an open procedure should be opted for
      better outcomes.

PMID- 27891032
TI  - Clinical anatomy and significance of the thoracic intervertebral foramen: A
      cadaveric study and review of the literature.
AB  - INTRODUCTION: The literature is lacking information on the anatomy and the
      osseous dimensions of the thoracic intervertebral foramen (IVF). We describe the
      anatomy of the broader area, and we proceed with morphometric data of the
      vertebrae and the foramina. Depiction of these features is provided with imaging
      and illustrations. The purpose of this paper is to survey and present the anatomy
      of the foramen as a whole and provide baseline statistical data. MATERIALS AND
      METHODS: We review relevant literature, and we present data obtained from
      skeletal samples of known population and sex. One hundred and nineteen thoracic
      vertebrae of ten cadaveric spines from the prefecture of Eastern Macedonia and
      Thrace, Greece, were selected. Statistical analysis measuring the vertical height
      and the foraminal width of each vertebra was made in accordance with sex.
      RESULTS: No statistically important differences referring to the descriptive data
      of both sexes were found. However, statistically, important positive correlation
      between the vertebral height and the foraminal width was observed, especially for
      men. The components of the foramen including arteries and veins passing through
      or neighboring it, and the spinal nerves and roots are described and depicted.
      CONCLUSIONS: The osseous thoracic IVF reveals a glimpse of the in vivo structure
      and alterations of its width may be present in back pain and other degenerative
      diseases. Although it is crucial for surgeries and other interventional
      procedures of the thoracic spine, little is known about the precise anatomy and
      dimensions of this anatomical landmark.

PMID- 27891033
TI  - Transthoracic approach for lesions involving the anterior dorsal spine: A
      multidisciplinary approach with good outcomes.
AB  - INTRODUCTION: Anterior approach provides excellent visualization and access to
      the anterior thoracic spine. It may be used alone, in combination with a
      posterior midline approach or in a staged or sequential fashion. AIMS: To analyse
      our institutional experience in transthoracic approaches and to determine the
      safety and benefit of this approach in our patient series. MATERIALS AND METHODS:
      A total of 16 patients were operated for varying lesions of body of dorsal
      vertebra by the transthoracic approach. The study was for a period of 5 years
      from January 2011 to December 2015. Patients age ranged from 25 to 61 years with
      an average of 36.4 yrs. There were 7 males and 9 females. In our series 9
      patients had Kochs spine, 4 patients were traumatic fracture spine and 3 had
      neoplastic lesion. Majority of patients had multiple symptoms with backache being
      present in all patients. RESULTS: There was one post operative mortality which
      was unrelated to surgery. One patient had post operative delayed kyphosis.
      Remaining patients improved in their symptoms following surgery. CONCLUSION: With
      careful coordination by thoracic surgeons, neurospinal surgeons and
      anaesthetists, the anterior spine approach for dorsal spine is safe and
      effective. Adequate preoperative evaluation should stratify the risk and
      institute measures to reduce it. Accurate surgical planning and careful surgical
      technique are the key to yield a good outcome and to reduce the risk of
      complications.

PMID- 27891034
TI  - The anatomical perspective of human occipital condyle in relation to the
      hypoglossal canal, condylar canal, and jugular foramen and its surgical
      significance.
AB  - BACKGROUND: The transcondylar approach (TCA) has gained importance in recent era
      which enables shorter and direct route to access the lesions ventral to the
      brainstem. The important step in this approach is resection of the occipital
      condyle (OC). The detailed knowledge of bony anatomy of OC and its relation to
      the hypoglossal canal (HC), condylar canal (CC), and jugular foramen (JF) is very
      important to avoid any iatrogenic injury during craniovertebral surgeries. The
      aim of the present study is to conduct a morphometric and morphological study and
      note the variations of the OC and the structures surrounding it in North Indian
      population. MATERIALS AND METHODS: The study was carried out on 100 OC.
      Morphometric measurements of OC and the distances of HC and JF from the posterior
      end of OC were noted. In addition, the extent of the HC and JF in relation to OC,
      presence or absence of CC, shape of the OC, and its articular facet were also
      noted. RESULTS: The incidence of short OC was seen in 13% skulls. The most common
      shape of OC was oval or rhomboid. Even though the articular facet was convex in
      majority of skulls but flat (10%) and concave (1%) were also observed. The
      external and internal distance of HC from the posterior end of OC was13.83 mm and
      10.66 mm on the right side and 15.02 mm and 11.89 mm on the left side. The OC was
      related in its middle 1/3 to the HC in 15% skulls and to the whole extent of JF
      in 3% skulls. Thirty-four percent skulls displayed the septa in the HC. The CC
      was present bilaterally in 38% skulls and unilaterally in 40% skulls. CONCLUSION:
      The OC and related structures such as HC, CC, and JF are likely to have
      variations in respect to morphometry and morphology. This study may prove helpful
      to neurosurgeons operating in this field, especially during TCA where
      neurovascular structures emerging from these canals and foramen are more
      vulnerable to injury.

PMID- 27891035
TI  - Intradiscal and intra-articular facet infiltrations with plasma rich in growth
      factors reduce pain in patients with chronic low back pain.
AB  - CONTEXT: Low back pain (LBP) is a complex and disabling condition, and its
      treatment becomes a challenge. AIMS: The aim of our study was to assess the
      clinical outcome of plasma rich in growth factors (PRGF-Endoret) infiltrations
      (one intradiscal, one intra-articular facet, and one transforaminal epidural
      injection) under fluoroscopic guidance-control in patients with chronic LBP. PRGF
      Endoret which has been shown to be an efficient treatment to reduce joint pain.
      SETTINGS AND DESIGN: The study was designed as an observational retrospective
      pilot study. Eighty-six patients with a history of chronic LBP and degenerative
      disease of the lumbar spine who met inclusion and exclusion criteria were
      recruited between December 2010 and January 2012. SUBJECTS AND METHODS: One
      intradiscal, one intra-articular facet, and one transforaminal epidural injection
      of PRGF-Endoret under fluoroscopic guidance-control were carried out in 86
      patients with chronic LBP in the operating theater setting. STATISTICAL ANALYSIS
      USED: Descriptive statistics were performed using absolute and relative frequency
      distributions for qualitative variables and mean values and standard deviations
      for quantitative variables. The nonparametric Friedman statistical test was used
      to determine the possible differences between baseline and different follow-up
      time points on pain reduction after treatment. RESULTS: Pain assessment was
      determined using a visual analog scale (VAS) at the first visit before (baseline)
      and after the procedure at 1, 3, and 6 months. The pain reduction after the PRGF
      Endoret injections showed a statistically significant drop from 8.4 +/- 1.1
      before the treatment to 4 +/- 2.6, 1.7 +/- 2.3, and 0.8 +/- 1.7 at 1, 3, and 6
      months after the treatment, respectively, with respect to all the time
      evaluations (P < 0.0001) except for the pain reduction between the 3rd and 6th
      month whose signification was lower (P < 0.05). The analysis of the VAS over time
      showed that at the end point of the study (6 months), 91% of patients showed an
      excellent score, 8.1% showed a moderate improvement, and 1.2% were in the
      inefficient score. CONCLUSIONS: Fluoroscopy-guided infiltrations of
      intervertebral discs and facet joints with PRGF in patients with chronic LBP
      resulted in significant pain reduction assessed by VAS.

PMID- 27891037
TI  - Revisiting cruciate paralysis: A case report and systematic review.
AB  - OBJECTIVE: Cruciate paralysis is a rare, poorly understood condition of the upper
      craniovertebral junction that allows for selective paralysis of the upper
      extremities while sparing the lower extremities. Reported cases are few and best
      treatment practices remain up for debate. The purpose of this study was to
      conduct a systemic literature review in an attempt to identify prognostic
      predictors and outcome trends associated with cases previously reported in the
      literature. MATERIALS AND METHODS: We conducted a systematic literature review
      for all cases using the term "Cruciate Paralysis," reviewing a total of 37
      reported cases. All outcomes were assigned a numerical value based on examination
      at the last follow-up. These numerical values were further analyzed and tested
      for statistical significance. RESULTS: Of the 37 cases, 78.4% were of traumatic
      causes. Of these, there were considerably worse outcomes associated with patients
      over the age of 65 years (P < 0.001). Those patients undergoing surgical
      treatment showed potentially worse outcomes, with a P value approaching
      significance at P = 0.08. CONCLUSION: Numerous cases of trauma-associated
      cruciate paralysis have been reported in the literature; however, there remains a
      strong need for further study of the condition. While certain risk factors can be
      elicited from currently reported studies, insignificant data exist to make any
      sound conclusion concerning whether surgical intervention is always the best
      method of treatment.

PMID- 27891036
TI  - Complete morphometric analysis of jugular foramen and its clinical implications.
AB  - INTRODUCTION: Tumors affecting structures in the vicinity of jugular foramen such
      as glomus jugulare require microsurgical approach to access this region. These
      tumors tend to alter the normal architecture of the jugular foramen by invading
      it. Therefore, it is not feasible to have correct anatomic visualization of the
      foramen in the presence of such pathologies. Hence, a comprehensive knowledge of
      the jugular foramen is needed by all the neurosurgeons while doing surgery in
      this region. AIM: Due to the inadequate knowledge of the accurate morphology of
      the jugular foramen in different sexes, the aim of this osteological study was to
      provide a complete morphometry including gender differences and describe some
      morphological characteristics of the jugular foramen in an adult Indian
      population. MATERIALS AND METHODS: The study was done on 114 adult human dry
      skulls (63 males and 51 females) collected from the osteology museum in the
      department. Various dimensions of both endo- and exocranial aspect of jugular
      foramen were measured. Presence and absence of domed bony roof of jugular fossa
      and compartmentalization of jugular foramen were also noticed. Statistical
      analysis was done using Chi-square test and Student's t-test in SPSS version 23.
      RESULTS: All the parameters of right jugular foramen were greater than the left
      side, except the distance of stylomastoid foramen from lateral margin of jugular
      foramen (SMJF) which was greater on the left side. Gender differences between
      various measurements of jugular foramen, presence of dome of jugular fossa, and
      compartmentalization patterns were reported. CONCLUSION: This study gives
      knowledge about the various parameters, anatomical variations of jugular foramen
      in both sexes of an adult Indian population, and its clinical impact on the
      surgeries of this region.

PMID- 27891038
TI  - Accessory atlantoaxial ligament avulsion fracture of the axis: Are there any
      clinical implications?
AB  - Injuries to the craniocervical support structures are frequently observed in
      neurotrauma cases. Stability of this region is of vital importance. Literature
      has mainly focused on three major ligaments of the craniocervical junction: The
      tectorial membrane, the transverse ligament, and the alar ligaments. However, the
      accessory atlantoaxial ligament (ALL) also seems to be involved in craniocervical
      stability as shown in cadaveric specimens. Still, the biomechanical importance of
      this structure needs to be determined, especially in trauma settings. Here, we
      describe a case of isolated traumatic injury to this structure and discuss the
      clinical outcome. A 64-year-old polytrauma patient with a remarkable avulsion
      fracture at the site of the insertion of the ALL was admitted to our center. We
      evaluated the patient both clinical and radiological at admission, after 3 months
      and after 1 year. We clinically assessed the upper cervical rotational stability
      using the cervical flexion-rotation test. We observed no rotational instability
      or any other clinical repercussions at the long-term after an isolated ALL
      injury. This case shows that isolated traumatic damage to the ALL is possible.
      Unilateral damage to the ALL probably does not cause rotational instability of
      the craniocervical junction. In case a similar avulsion fracture is observed, we
      recommend performing a magnetic resonance imaging of the craniovertebral region
      to assess for any ligamentous lesions.

PMID- 27891039
TI  - Chronic Pseudomonas aeruginosa cervical osteomyelitis.
AB  - Pseudomonas aeruginosa is a rare cause of osteomyelitis of the cervical spine and
      is usually seen in the background of intravenous drug use and immunocompromised
      state. Very few cases of osteomyelitis of the cervical spine caused by
      pseudomonas aeruginosa have been reported in otherwise healthy patients. This is
      a case presentation of a young female, who in the absence of known risk factors
      for cervical osteomyelitis presented with progressively worsening neurological
      signs and symptoms.

PMID- 27891040
TI  - Inadvertent injection of potassium chloride instead of sodium chloride during
      treatment of chronic low back ache with epidural injection leading to paraplegia.
AB  - Epidural injection of steroid is given for back pain resistant to other
      conservative management. Normal saline (NS) is used as diluent in 80 mg
      methylprednisolone and a local anesthetic. Due to a similar looking ampoule of NS
      and potassium chloride (KCl), there is a probability of accidental use of KCl
      instead of NS. We present a case of a 50-year-old male patient having low back
      ache refractory to other conservative treatments. Epidural injection of steroid
      was given, but accidently KCl was mixed with methylprednisolone instead of NS. He
      developed severe cramps in the lower limbs, pruritus, and sweating, and finally
      paraplegia. Electrocardiography and blood showed features suggestive of
      hyperkalemia. He was given calcium gluconate and potassium chelating agent along
      with supportive measures. The patient recovered within 8 h. It is concluded that
      calcium gluconate and potassium chelating agent can be used if accidentally KCl
      is injected in epidural space.

PMID- 27891041
TI  - Spinal intradural hydatid cyst causing arachnoiditis: A rare etiology of cauda
      equina syndrome.
AB  - This study aims to focus on a rare presentation of spinal hydatid cyst as cauda
      equine syndrome and misdiagnosed as intradural extramedullary (IDEM) benign
      lesion on magnetic resonance imaging. In this article, we report a case of spinal
      hydatid cyst masquerading as IDEM tumor, and intraoperatively, we accidently find
      clumped granuloma with severe arachnoiditis and hydatid cyst in lumber region,
      which was present as bilateral S1 radiculopathy with cauda equina syndrome. An 11
      year-old boy who presented with symptoms and signs of cauda equina syndrome and
      planned for surgical excision. His radiological impression was IDEM possibly
      neurofibroma. To our surprise, we found multiple intradural cystic lesions with
      arachnoiditis. Dissecting in plane cyst was flushed out, and surgical cavity was
      irrigated with 3% saline. Postoperatively histopathology and serum tests
      confirmed the diagnosis of hydatid cyst. Hydatid disease is rare cause of cauda
      equine syndrome which can be miss diagnosed on radiological investigations. A
      high index of suspicion should be kept especially in a young patient from the
      Indian subcontinent.

PMID- 27891042
TI  - Spinal cysticercosis: A report of two cases with review of literature.
AB  - Neurocysticercosis is the most common parasitic infection of the central nervous
      system worldwide. However, Cysticercosis affecting the spine is considered
      extremely rare. We report two cases of spinal cysticercosis with review of
      literature.

PMID- 27891043
TI  - Time Perspectives Predict Mood States and Satisfaction with Life over and above
      Personality.
AB  - The present study aimed to test the incremental validity of Time Perspective (TP)
      scales in predicting satisfaction with life and mood, over and above the Big Five
      personality traits. It also investigated whether the new TP construct of Future
      Negative perspective contributed to prediction of these outcomes. Participants (N
      = 265) completed four measures: Satisfaction With Life Scale (SWLS), UWIST Mood
      Adjective Checklist (UMACL), a modified Zimbardo Time Perspective Inventory
      (ZTPI), and NEO-Five Factor Inventory (NEO-FFI). Results confirmed the
      incremental validity of TP, although Big Five dimensions were independently
      predictive of life satisfaction and certain mood scales. Past Negative TP was the
      strongest single predictor of life satisfaction. However, Future Negative TP was
      be the strongest mood predictor from the TP universe, after controlling for the
      Big Five and remaining TP dimensions. Findings suggest that TP is an important
      aspect of personality for understanding individual differences in well-being.

PMID- 27891044
TI  - An Investigation of Loneliness and Perceived Social Support Among Single and
      Partnered Young Adults.
AB  - This study investigated the possible differences between single individuals and
      individuals in nonmarital romantic relationships in the domains of emotional
      (romantic and family) and social loneliness, and of perceived social support from
      family, friends and significant others. Based on a Polish university-student
      sample of 315 participants (167 women and 148 men) aged 19 to 25 years (M =
      21.90, SD = 2.15), single relationship status was related to greater romantic and
      family loneliness, and to less perceived social support from significant others
      and family. Women reported a lower level of social loneliness and a higher level
      of perceived social support in comparison to men. Relationship status interacted
      with gender in predicting perceived social support from significant others and
      friends. Finally, the duration of remaining single and significant others'
      support were found to be predictive of single young adults' romantic loneliness.
      In addition, perceived social support from family and significant others were
      found to moderate the relationship between the duration of remaining single and
      romantic loneliness. In particular, high family support and medium-high support
      from significant others mitigated the negative impact of being single for a long
      time on romantic loneliness.

PMID- 27891045
TI  - Reinforced Angle-based Multicategory Support Vector Machines.
AB  - The Support Vector Machine (SVM) is a very popular classification tool with many
      successful applications. It was originally designed for binary problems with
      desirable theoretical properties. Although there exist various Multicategory SVM
      (MSVM) extensions in the literature, some challenges remain. In particular, most
      existing MSVMs make use of k classification functions for a k-class problem, and
      the corresponding optimization problems are typically handled by existing
      quadratic programming solvers. In this paper, we propose a new group of MSVMs,
      namely the Reinforced Angle-based MSVMs (RAMSVMs), using an angle-based
      prediction rule with k - 1 functions directly. We prove that RAMSVMs can enjoy
      Fisher consistency. Moreover, we show that the RAMSVM can be implemented using
      the very efficient coordinate descent algorithm on its dual problem. Numerical
      experiments demonstrate that our method is highly competitive in terms of
      computational speed, as well as classification prediction performance.
      Supplemental materials for the article are available online.

PMID- 27891046
TI  - Psychological Inflexibility and Child Anxiety.
AB  - Psychological flexibility is the main outcome of acceptance commitment therapy.
      Insight into the usefulness of measuring psychological flexibility is an
      important step to enable studies on the effectiveness of acceptance commitment
      therapy in middle-aged children (8-10 years). For this purpose, we examined the
      factor structure, the construct validity and the reliability of the Avoidance and
      Fusion Questionnaire for Youth. The Avoidance and Fusion Questionnaire for Youth
      taps psychological inflexibility (the opposite of psychological flexibility) in
      children and adolescents. Although the questionnaire has been extensively
      validated in older children, this is not the case for middle-aged children. The
      Avoidance and Fusion Questionnaire for Youth contains 17 items and is constituted
      of the subscales cognitive fusion, experiential avoidance and behavioral
      ineffectiveness. A shortened 8-item version also exists, the Avoidance and Fusion
      Questionnaire for Youth-8, which does not distinguish between these subscales. We
      performed a confirmatory factor analysis. Additionally, we assessed the
      relationship between psychological flexibility and child anxiety. Children, aged
      8-10 years, were recruited via regular primary schools. Of the 459 approached
      children, 267 (58 %) parents signed informed consents for their children (Age: M
      = 9.18; SD = .79; Sex: nboys = 137, 51 %). Children completed the questionnaires
      during regular classes. In this sample, the 17-item version of the Avoidance and
      Fusion Questionnaire for Youth was less appropriate for measuring psychological
      inflexibility than the 8-item version. Furthermore, we found a significant
      positive relationship between psychological inflexibility and child anxiety. We
      argue that acceptance commitment therapy would be an interesting candidate for
      intervening early on in dysfunctional child anxiety, as acceptance commitment
      therapy's cognitive elements require cognitive skills that children are likely to
      master early on.

PMID- 27891047
TI  - Endoscopic Submucosal Dissection Outcomes for Gastroesophageal Tumors in Low
      Volume Units: A Multicenter Survey.
AB  - Background and Aims. Endoscopic submucosal dissection (ESD) outcomes have
      traditionally been reported from high volume centers in East Asia. Data from low
      volume centers in other parts of Asia remain sparse. Methods. A retrospective
      survey with a structured questionnaire of 5 tertiary centers in 3 countries in
      South East Asia was conducted. Details of training and clinical outcomes of ESD
      cases, with follow-up data from these centers, were analyzed. Results. Seven
      endoscopists from the 5 centers performed a total of 35 cases of ESD in the upper
      gastrointestinal tract (UGIT) over a 6-year duration. Details of the lesions
      excised were as follows: median size was 20 mm, morphologically 20 (68.6%) were
      flat/depressed and 6 (17.1%) were submucosal, and histologically 27 (77.1%) were
      neoplastic. The median duration of ESD procedures was 105 minutes, with an en
      bloc resection rate of 91.4%. There was 1 (2.9%) case of delayed bleeding, but no
      perforation nor mortality in any of the cases. The recurrence rate after ESD was
      5.7%. A prolonged ESD duration was influenced by a larger size of lesion (25 mm,
      p = 0.02) but not by factors related to the training experience of endoscopists.
      Conclusions. ESD in the UGIT is feasible and safe in low volume centers in Asia.

PMID- 27891048
TI  - Metabolic Signatures of Lung Cancer in Sputum and Exhaled Breath Condensate
      Detected by 1H Magnetic Resonance Spectroscopy: A Feasibility Study.
AB  - OBJECTIVES: Lung cancer is one of the most lethal cancers. Currently, there are
      no biomarkers for early detection, monitoring treatment response, and detecting
      recurrent lung cancer. We undertook this study to determine if 1H magnetic
      resonance spectroscopy (MRS) of sputum and exhaled breath condensate (EBC), as a
      noninvasive tool, can identify metabolic biomarkers of lung cancer. MATERIALS AND
      METHODS: Sputum and EBC samples were collected from 20 patients, comprising
      patients with pathologically confirmed non-small cell lung cancer (n = 10) and
      patients with benign respiratory conditions (n = 10). Both sputum and EBC samples
      were collected from 18 patients; 2 patients provided EBC samples only. 1H MR
      spectra were obtained on a Bruker Avance 400 MHz nuclear magnetic resonance (NMR)
      spectrometer. Sputum samples were further confirmed cytologically to distinguish
      between true sputum and saliva. RESULTS: In the EBC samples, median
      concentrations of propionate, ethanol, acetate, and acetone were higher in lung
      cancer patients compared to the patients with benign conditions. Median
      concentration of methanol was lower in lung cancer patients (0.028 mM) than in
      patients with benign conditions (0.067 mM; P = 0.028). In the combined sputum and
      saliva and the cytologically confirmed sputum samples, median concentrations of N
      acetyl sugars, glycoprotein, propionate, lysine, acetate, and formate were lower
      in the lung cancer patients than in patients with benign conditions. Glucose was
      found to be consistently absent in the combined sputum and saliva samples (88%)
      as well as in the cytologically confirmed sputum samples (86%) of lung cancer
      patients. CONCLUSION: Absence of glucose in sputum and lower concentrations of
      methanol in EBC of lung cancer patients discerned by 1H MRS may serve as
      metabolic biomarkers of lung cancer for early detection, monitoring treatment
      response, and detecting recurrence.

PMID- 27891049
TI  - Quantifying the Seafood Consumption Patterns of Recreational Anglers in
      Charleston and Berkeley Counties, South Carolina.
AB  - This study was designed to provide self-reported data on the frequency of fish
      consumption and shellfish consumption in Charleston and Berkeley (CB) counties,
      South Carolina. While commercial fishing and recreational fishing have played an
      important role in the culture and history of the area, information on the
      specific patterns of consumption by recreational anglers has been previously
      unavailable. The pilot data presented here will help determine the feasibility of
      a large-scale survey of seafood consumption in coastal South Carolina. The
      study's sampling frame consisted of CB county anglers who had purchased a
      recreational saltwater fishing license for the 2005/2006 year with oversampling
      in North Charleston. Survey recipients were asked to provide information on fish
      consumption and shellfish consumption, general angling habits, perception of
      water and fishing quality, and demographics. Of the 2500 individuals who were
      sent questionnaires, about one-fourth responded. Respondents were generally
      white, middle, or upper class and highly educated. The majority fished by boat
      and most often ate flounder, spotted sea trout, and red drum. Most respondents
      ate shrimp several times a month and also supplemented their recreational catch
      with seafood purchased from grocery stores, markets, and restaurants. Almost all
      respondents had eaten some seafood in the last year, and more than one-fourth ate
      seafood twice a week or more. Most anglers responded positively about the area's
      fishing and water qualities, but many referred to areas where they would hesitate
      to eat their catch. Further research may need to incorporate direct distribution
      of surveys to underrepresented groups and financial incentives to encompass a
      more diverse population of anglers.

PMID- 27891050
TI  - Evaluating the Effect of Oxygen Concentrations on Antibiotic Sensitivity, Growth,
      and Biofilm Formation of Human Pathogens.
AB  - Standard antimicrobial susceptibility tests are performed in vitro under normal
      room oxygen conditions to predict the in vivo effectiveness of antimicrobial
      therapy. The aim of this study was to conduct a comprehensive analysis of the
      effect of different oxygen levels on the antibiotic susceptibility of two strains
      of Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae. It
      was found that anoxic conditions caused reduced sensitivity of bacteria to
      aminoglycoside antibiotics in four of six bacteria used in the study. In
      addition, oxygen limitation decreased the susceptibility of P. aeruginosa strains
      and K. pneumoniae strains to piperacillin/tazobactam and azithromycin,
      respectively. In contrast, five of six bacteria became more susceptible to
      tetracycline antibiotics under oxygen-limiting conditions. Our data highlight the
      importance of considering the potential in vivo oxygen levels within the
      infection site when setting susceptibility breakpoints for evaluating the
      therapeutic potential of a drug and its effect on antibiotic sensitivity of the
      pathogen.

PMID- 27891051
TI  - Analysis of Helicobacter pylori Prevalence in Chittagong, Bangladesh, Based on
      PCR and CLO Test.
AB  - The pathogenic bacterium Helicobacter pylori is a causative agent of gastric
      diseases in Bangladesh as well as throughout the world. This study aimed at
      analyzing the prevalence of H. pylori infection among dyspeptic patients in
      Chittagong, the second most populous city of Bangladesh, using 16S rRNA-based H.
      pylori-specific Polymerase Chain Reaction and Campylobacter-like organism test.
      We found that 67% of the population under study was positive for H. pylori
      infection. Gastric ulcer and duodenal ulcer disease showed statistically
      significant association with H. pylori infection; however, no association of H.
      pylori infection was observed in terms of age and gender. This study would play a
      crucial role in managing H. pylori-induced gastric diseases by understanding the
      current trend of H. pylori infection in the Chittagong region of Bangladesh.

PMID- 27891052
TI  - From Ethanol to Salsolinol: Role of Ethanol Metabolites in the Effects of
      Ethanol.
AB  - In spite of the global reputation of ethanol as the psychopharmacologically
      active ingredient of alcoholic drinks, the neurobiological basis of the central
      effects of ethanol still presents some dark sides due to a number of unanswered
      questions related to both its precise mechanism of action and its metabolism.
      Accordingly, ethanol represents the interesting example of a compound whose
      actions cannot be explained as simply due to the involvement of a single
      receptor/neurotransmitter, a scenario further complicated by the robust evidence
      that two main metabolites, acetaldehyde and salsolinol, exert many effects
      similar to those of their parent compound. The present review recapitulates, in a
      perspective manner, the major and most recent advances that in the last decades
      boosted a significant growth in the understanding on the role of ethanol
      metabolism, in particular, in the neurobiological basis of its central effects.

PMID- 27891054
TI  - Patellofemoral Joint Arthroplasty: Our Experience in Isolated Patellofemoral and
      Bicompartmental Arthritic Knees.
AB  - INTRODUCTION: Isolated patellofemoral (PF) arthritis is rare, and there is no
      complete agreement about the best surgical treatment. The operative treatments
      are total knee arthroplasty and patellofemoral replacement (PFR). The incidence
      of many early complications of PF arthroplasty has decreased with the
      introduction of newer designs. Nowadays, the main cause of revision surgery is
      the progression of tibiofemoral osteoarthritis. In the past, PF arthroplasty was
      contraindicated in patients with evidence of osteoarthritis or pain in medial or
      lateral tibiofemoral compartments. The improvement in implant designs and
      surgical techniques has allowed the addition of a monocompartmental arthroplasty
      for the medial or lateral tibiofemoral compartment. In this work, we evaluate our
      first experience with PF arthroplasty and its combination with unicompartmental
      knee arthroplasty. MATERIALS AND METHODS: From May 2014 to March 2016, we treated
      14 patients. An isolated PF arthroplasty was performed in six knees (five
      patients), and a combined PF and unicompartmental knee arthroplasty was performed
      in nine cases. We observed a significant improvement in the clinical and
      functional Knee Society Scores (KSSs) after surgery in our patients. RESULTS: We
      obtained good results in our cases both for clinical and functional KSSs.
      Patellar clunk was recorded in one case. DISCUSSION AND CONCLUSION: We are going
      toward a new attitude in which partial osteoarthritic changes could be treated
      with partial resurfacing prosthetic solutions such as unicompartmental, bi
      unicompartmental or PFR alone, or unicompartmental combined, which respects the
      cruciates and achieves maximal bone preservation, which is vital, particularly,
      for young patients.

PMID- 27891053
TI  - H3 and H4 Lysine Acetylation Correlates with Developmental and Experimentally
      Induced Adult Experience-Dependent Plasticity in the Mouse Visual Cortex.
AB  - Histone posttranslational modifications play a fundamental role in orchestrating
      gene expression. In this work, we analyzed the acetylation of H3 and H4 histones
      (AcH3-AcH4) and its modulation by visual experience in the mouse visual cortex
      (VC) during normal development and in two experimental conditions that restore
      juvenile-like plasticity levels in adults (fluoxetine treatment and enriched
      environment). We found that AcH3-AcH4 declines with age and is upregulated by
      treatments restoring plasticity in the adult. We also found that visual
      experience modulates AcH3-AcH4 in young and adult plasticity-restored mice but
      not in untreated ones. Finally, we showed that the transporter vGAT is
      downregulated in adult plasticity-restored models. In summary, we identified a
      dynamic regulation of AcH3-AcH4, which is associated with high plasticity levels
      and enhanced by visual experience. These data, along with recent ones, indicate
      H3-H4 acetylation as a central hub in the control of experience-dependent
      plasticity in the VC.

PMID- 27891057
TI  - Key Difficulties Associated with Cancer Biology.

PMID- 27891055
TI  - Imaging Guidance Improves the Results of Viscosupplementation with HANOX-M-XL in
      Patients with Ankle Osteoarthritis: Results of a Clinical Survey in 50 Patients
      Treated in Daily Practice.
AB  - BACKGROUND: The objective of this survey was to assess retrospectively the
      interest of performing viscosupplementation using imaging guidance in patients
      suffering from ankle osteoarthritis (OA). PATIENTS AND METHODS: This is a
      multicenter retrospective survey using a standardized questionnaire. Fifty
      patients suffering from ankle OA and treated, in daily clinical practice, with a
      single intra-articular injection of a novel viscosupplement made of a combination
      of a non-animal cross-linked hyaluronan and mannitol, HANOX M-XL, were included
      in the survey. The injection procedure (imaging or landmark guidance),
      demographic data, patient's self-evaluation of pain, satisfaction, treatment
      efficacy, and tolerability were collected. Predictive factors of both efficacy
      and patient's satisfaction were investigated. RESULTS: The percentages of
      patients very satisfied/satisfied and not really satisfied/dissatisfied with the
      treatment were 68% and 32%, respectively. Efficacy was rated as very good, good,
      moderate, and poor by 38%, 30%, 12%, and 20% of the cases, respectively. Efficacy
      was unrelated to gender and age and was highly correlated with pain score (P <
      0.0001). In satisfied patients, the decrease in consumption of analgesics/non
      steroidal anti-inflammatory drugs was >75% in 64% of the cases. Efficacy was
      significantly different with regard to imaging guidance. There was a
      statistically significant difference in efficacy and satisfaction between
      landmark-guided and imaging-guided injections (P = 0.02). The success rate was
      2.3 times higher in the imaging-guided group than in the landmark-guided group.
      No significant difference was found between patients injected under fluoroscopy
      or ultrasound guidance, despite a trend favoring ultrasound (P = 0.09).
      Tolerability was rated as very good/good in 47 patients, moderate in two, and
      poor in one and was unrelated to the type of guidance. CONCLUSION: This
      preliminary study suggests that the use of imaging guidance significantly
      optimizes the success rate of ankle viscosupplementation. No safety concern was
      observed. LEVEL OF EVIDENCE: III.

PMID- 27891056
TI  - Eradication of Helicobacter pylori Infection Restores ki67, p53, and Cyclin D1
      Immunoreactivity in the Human Gastric Epithelium.
AB  - INTRODUCTION: We evaluated the effect of Helicobacter pylori (HP) eradication on
      p53, cyclin D1 expression, and cell proliferation in gastric mucosa. MATERIALS
      AND METHODS: We assessed p53, cyclin D1, and ki67 immunoexpression in gastric
      mucosa from 31 HP chronic gastritis patients and 12 controls. Reassessment was
      performed 6 months after successful HP eradication. RESULTS: Successful
      eradication resulted in significant decrease of p53 (1.53 +/- 0.16 vs 0.83 +/-
      0.19, P = 0.01) and ki67 (9.84 +/- 0.96 vs 4.77 +/- 0.27, P < 0.001) staining in
      the antrum. Similarly, p53 immunoreactivity significantly decreased in the corpus
      (1.27 +/- 0.20 vs 0.46 +/- 0.15, P = 0.02), while there was a trend for decreased
      corpus cyclin D1 and ki67 expression (0.17 +/- 0.07 vs 0.0, P = 0.08 and 8.71 +/-
      1.24 vs 5.85 +/- 0.54, P = 0.09, respectively). Importantly, after successful HP
      eradication, the immunoreactivity of the studied parameters was similar to that
      of controls. CONCLUSION: Successful HP infection eradication restores p53, cyclin
      D1, and ki67 immunoreactivity in the gastric mucosa to the level of controls.

PMID- 27891058
TI  - IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity.
AB  - Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan
      catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects
      on various diseases including cancer and autoimmunity. Here, we review what is
      known about the direct connections between IDO2 and immune function, particularly
      in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis
      and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory
      mediator of autoimmunity, with a functional phenotype distinct from IDO1. IDO2 is
      expressed in antigen-presenting cells, including B cells and dendritic cells, but
      affects inflammatory responses in the autoimmune context specifically by acting
      in B cells to modulate T cell help in multiple model systems. Given that
      expression of IDO2 can lead to exacerbation of inflammatory responses, IDO2
      should be considered a potential therapeutic target for autoimmune disorders.

PMID- 27891059
TI  - Ethnic Identity Attachment and Motivation for Weight Loss and Exercise Among
      Rural, Overweight, African-American Women.
AB  - Rural and minority women are disproportionately impacted by the obesity epidemic;
      however, little research has studied the intersection of these disparity groups.
      The purpose of this study was to examine the influence of racial identity on
      motivation for weight loss and exercise among rural, African-American women with
      an obesity-linked chronic disease. A total of 154 African-American women were
      recruited from the patient population of a Federally Qualified Health Center in
      the rural South to complete a questionnaire battery including the Multigroup
      Ethnic Identity Measure and separate assessments of motivation for weight loss
      and exercise. Multivariate analyses, controlling for age, education status,
      insurance status, and body mass index revealed that attachment to ethnic identity
      was predictive of motivation for exercise but not for weight loss. Our findings
      suggest that attachment to ethnic identity may be an important factor in
      motivation for change among African-American women, particularly with respect to
      exercise, with direct implications for the development of culturally and
      geographically tailored weight loss interventions.

PMID- 27891061
TI  - Noninvasive Positive Pressure Ventilation in Chronic Heart Failure.
AB  - Instruction and Objectives. Noninvasive positive pressure ventilation (NPPV)
      alleviates sleep-disordered breathing (SDB) and it may improve cardiac function
      in SDB patients. Because large randomized controlled trials directly evaluating
      the impact of NPPV on cardiac function are lacking, we conducted a meta-analysis
      of published data on effectiveness of NPPV in improving cardiac function in
      patients with chronic heart failure regardless of SDB presence. Methods.
      Controlled trials were identified in PubMed, OVID, and EMBASE databases. Both
      fixed and randomized models were used in meta-analysis with primary outcomes of
      left ventricular ejection fraction (LVEF). Results. Nineteen studies were
      included with a total of 843 patients. Compared to standard medical treatment
      (SMT) plus sham-NPPV or SMT only, NPPV plus SMT was associated with improvement
      in LVEF (weighted mean difference 5.34, 95% CI, [3.85,6.82]; P < 0.00001) and
      plasma brain natriuretic peptide (BNP) level (weighted mean difference -117.37,
      95% CI, [-227.22, -7.52]; P = 0.04) and no influence on overall mortality (RR
      1.00, 95% CI, [0.96,1.04]; P = 0.95). Conclusions. In the present meta-analysis,
      use of NPPV plus SMT improved LVEF and reduced plasma BNP level but did not
      improve overall mortality in patients with chronic heart failure.

PMID- 27891062
TI  - Results from 10 Years of a CBT Pain Self-Management Outpatient Program for
      Complex Chronic Conditions.
AB  - Background. Traditional unimodal interventions may be insufficient for treating
      complex pain, as they do not address cognitive and behavioural contributors to
      pain. Cognitive Behavioural Therapy (CBT) and physical exercise (PE) are
      empirically supported treatments that can reduce pain and improve quality of
      life. Objectives. To examine the outcomes of a pain self-management outpatient
      program based on CBT and PE at a rehabilitation hospital in Toronto, Ontario.
      Methods. The pain management group (PMG) consisted of 20 sessions over 10 weeks.
      The intervention consisted of four components: education, cognitive behavioural
      skills, exercise, and self-management strategies. Outcome measures included the
      sensory, affective, and intensity of pain experience, depression, anxiety, pain
      disability, active and passive coping style, and general health functioning.
      Results. From 2002 to 2011, 36 PMGs were run. In total, 311 patients entered the
      program and 214 completed it. Paired t-tests showed significant pre- to
      posttreatment improvements in all outcomes measured. Patient outcomes did not
      differ according to the number or type of diagnoses. Both before and after
      treatment, women reported more active coping than men. Discussion. The PMGs
      improved pain self-management for patients with complex pain. Future research
      should use a randomized controlled design to better understand the outcomes of
      PMGs.

PMID- 27891060
TI  - Human metapneumovirus in the preterm neonate: current perspectives.
AB  - Premature birth (<37 weeks gestation) occurs in ~11% of all births in the US.
      These infants are at risk of chronic lung disease and respiratory conditions,
      including bronchopulmonary dysplasia. Respiratory viruses are important causes of
      acute respiratory illness (ARI) in preterm infants, leading to rehospitalization,
      increased health care burden, and long-term morbidity. Human metapneumovirus
      (HMPV) is a paramyxovirus discovered in 2001 that is related to respiratory
      syncytial virus. Epidemiologic studies show that HMPV is a leading cause of ARI
      in children and adults worldwide. Prematurity is a major risk factor for severe
      HMPV disease, requiring hospitalization. Moreover, limited data suggest that HMPV
      infection during infancy is associated with asthma and recurrent wheezing, which
      are common long-term pulmonary complication of prematurity. HMPV causes
      nosocomial outbreaks of ARI in hospitals and long-term care facilities, although
      there are few studies of the prevalence of HMPV in neonatal intensive care unit
      populations. HMPV is a common and important virus in premature infants, and
      caregivers for preterm infants should consider this virus in patients with acute
      respiratory symptoms.

PMID- 27891063
TI  - Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses
      glioblastoma growth and invasiveness.
AB  - BACKGROUND: Genomic instability is a hallmark of cancer cells, and this cellular
      phenomenon can emerge as a result of replicative stress. It is possible to take
      advantage of replicative stress, and enhance it in a targeted way to fight cancer
      cells. One of such strategies involves targeting the cell division cycle 7
      related protein kinase (CDC7), a protein with key roles in regulation of
      initiation of DNA replication. CDC7 overexpression is present in different
      cancers, and small molecule inhibitors of the CDC7 have well-documented anti
      tumor effects. Here, we aimed to test the potential of CDC7 inhibition as a new
      strategy for glioblastoma treatment. METHODS: PHA-767491 hydrochloride was used
      as the CDC7 inhibitor. Two glioblastoma cell lines (U87-MG and U251-MG) and a
      control cell line (3T3) were used to characterize the effects of CDC7 inhibition.
      The effect of CDC7 inhibition on cell viability, cell proliferation, apoptosis,
      migration, and invasion were analyzed. In addition, real-time PCR arrays were
      used to identify the differentially expressed genes in response to CDC7
      inhibition. RESULTS: Our results showed that CDC7 inhibition reduces glioblastoma
      cell viability, suppresses cell proliferation, and triggers apoptosis in
      glioblastoma cell lines. In addition, we determined that CDC7 inhibition also
      suppresses glioblastoma cell migration and invasion. To identify molecular
      targets of CDC7 inhibition, we used real-time PCR arrays, which showed
      dysregulation of several mRNAs and miRNAs. CONCLUSIONS: Taken together, our
      findings suggest that CDC7 inhibition is a promising strategy for treatment of
      glioblastoma.

PMID- 27891064
TI  - Proteomic based approach for characterizing 4-hydroxy-2-nonenal induced oxidation
      of buffalo (Bubalus bubalis) and goat (Capra hircus) meat myoglobins.
AB  - BACKGROUND: Myoglobin (Mb) is a sarcoplasmic heme protein primarily responsible
      for meat color and its chemistry is species specific. 4-hydroxy-2-nonenal (HNE)
      is a cytotoxic lipid derived aldehyde detected in meat and was reported to
      covalently adduct with nucleophilic histidine residues of Mb and predispose it to
      greater oxidation. However, no literature is available on characterization of
      lipid oxidation induced oxidation of Indian water buffalo (Bubalus bubalis) and
      goat (Capra hircus) myoglobins. METHODS: Present study characterize the Mb
      extracted from water buffalo and goat cardiac muscles using two-dimensional gel
      electrophoresis (2DE), OFFGEL electrophoresis and mass spectrometry (MS).
      Purified buffalo and goat bright red oxymyoglobin were reacted with HNE in-vitro
      at physiological pH (7.4) and temperature (37  degrees C) conditions and the
      formation of oxidised brown metmyoglobin was measured. The Mb-HNE adducts were
      detected using MALDI-TOF MS, whereas specific sites of adduction was determined
      using ESI-QTOF MS/MS. RESULTS: Purified buffalo and goat Mb samples revealed a
      molecular mass of 17,043.6 and 16,899.9 Daltons, respectively. The 2DE analysis
      exhibited 65 (sarcoplasmic protein extract) and 6 (pure Mb) differentially
      expressed (P < 0.05) protein spots between buffalo and goat samples. OFFGEL
      electrophoresis revealed an isoelectric point of 6.77 and 7.35 respectively, for
      buffalo and goat Mb's. In-vitro incubation of HNE with bright red buffalo and
      goat oxymyoglobin's at pH 7.4 and 37  degrees C resulted in pronounced (P < 0.05)
      oxidation and formation of brown metmyoglobin. MALDI-TOF MS analysis of Mb-HNE
      reaction mix revealed covalent binding (via Michael addition) of 3 and 5
      molecules of HNE with buffalo and goat Oxy-Mb's, respectively. ESI-QTOF MS/MS
      identified seven and nine histidine (HIS) residues of Mb that were readily
      adducted by HNE in buffalo and goat, respectively. CONCLUSION: The study
      demonstrated better redox stability of buffalo Mb than goat Mb. Our findings
      confirm the hypothesis that relative effect of HNE was greater for Mb's with 12
      +/- 1 HIS residues than Mb's with 9 HIS residues and helps meat processors in
      developing species-specific processing strategies to reduce the color
      variability.

PMID- 27891066
TI  - In Situ Evaluation of Calcium Phosphate Nucleation Kinetics and Pathways during
      Intra- and Extrafibrillar Mineralization of Collagen Matrices.
AB  - We revealed that nucleation sites within collagen fibrils determined pathways for
      calcium phosphate (CaP) nucleation and its transformation, from amorphous species
      to crystalline plates, during the biomineralization process. Using in situ small
      angle X-ray scattering (SAXS), we examined the nucleation and growth of CaP
      within collagen matrices and elucidated how a nucleation inhibitor, polyaspartic
      acid (pAsp), governs mineralization kinetics and pathways at multiple length
      scales. Mineralization without pAsp led initially to spherical aggregates of CaP
      in the entire extrafibrillar spaces. With time, the spherical aggregates
      transformed into plates at the outermost surface of the collagen matrix,
      preventing intrafibrillar mineralization inside. However, mineralization with
      pAsp led directly to the formation of intrafibrillar CaP plates with a spatial
      distribution gradient through the depth of the matrix. The results illuminate
      mineral nucleation kinetics and real-time nanoparticle distributions within
      organic matrices in solutions containing body fluid components. Because the
      macroscale mechanical properties of collagen matrices depend on their mineral
      content, phase, and arrangement at the nanoscale, this study contributes to
      better design and fabrication of biomaterials for regenerative medicine.

PMID- 27891065
TI  - Trends, causes, and risk factors of mortality among children under 5 in Ethiopia,
      1990-2013: findings from the Global Burden of Disease Study 2013.
AB  - BACKGROUND: Ethiopia has made remarkable progress in reducing child mortality
      over the last two decades. However, the under-5 mortality rate in Ethiopia is
      still higher than the under-5 mortality rates of several low- and middle-income
      countries (LMIC). On the other hand, the patterns and causes of child mortality
      have not been well investigated in Ethiopia. The objective of this study was to
      investigate the mortality trend, causes of death, and risk factors among children
      under 5 in Ethiopia during 1990-2013. METHODS: We used Global Burden of Disease
      (GBD) 2013 data. Spatiotemporal Gaussian Process Regression (GPR) was applied to
      generate best estimates of child mortality with 95% uncertainty intervals (UI).
      Causes of death by age groups, sex, and year were measured using Cause of Death
      Ensemble modeling (CODEm). For estimation of HIV/AIDS mortality rate, the
      modified UNAIDS EPP-SPECTRUM suite model was used. RESULTS: Between 1990 and 2013
      the under-5 mortality rate declined from 203.9 deaths/1000 live births to 74.4
      deaths/1000 live births with an annual rate of change of 4.6%, yielding a total
      reduction of 64%. Similarly, child (1-4 years), post-neonatal, and neonatal
      mortality rates declined by 75%, 64%, and 52%, respectively, between 1990 and
      2013. Lower respiratory tract infection (LRI), diarrheal diseases, and neonatal
      syndromes (preterm birth complications, neonatal encephalopathy, neonatal sepsis,
      and other neonatal disorders) accounted for 54% of the total under-5 deaths in
      2013. Under-5 mortality rates due to measles, diarrhea, malaria, protein-energy
      malnutrition, and iron-deficiency anemia declined by more than two-thirds between
      1990 and 2013. Among the causes of under-5 deaths, neonatal syndromes such as
      sepsis, preterm birth complications, and birth asphyxia ranked third to fifth in
      2013. Of all risk-attributable deaths in 1990, 25% of the total under-5 deaths
      (112,288/435,962) and 48% (112,288/232,199) of the deaths due to diarrhea, LRI,
      and other common infections were attributable to childhood wasting. Similarly,
      19% (43,759/229,333) of the total under-5 deaths and 45% (43,759/97,963) of the
      deaths due to diarrhea and LRI were attributable to wasting in 2013. Of the total
      diarrheal disease- and LRI-related deaths (n = 97,963) in 2013, 59%
      (57,923/97,963) of them were attributable to unsafe water supply, unsafe
      sanitation, household air pollution, and no handwashing with soap. CONCLUSIONS:
      LRI, diarrheal diseases, and neonatal syndromes remain the major causes of under
      5 deaths in Ethiopia. These findings call for better-integrated newborn and child
      survival interventions focusing on the main risk factors.

PMID- 27891068
TI  - Can Mouse Imaging Studies Bring Order to Autism Connectivity Chaos?
AB  - Functional Magnetic Resonance Imaging (fMRI) has consistently highlighted
      impaired or aberrant functional connectivity across brain regions of autism
      spectrum disorder (ASD) patients. However, the manifestation and neural
      substrates of these alterations are highly heterogeneous and often conflicting.
      Moreover, their neurobiological underpinnings and etiopathological significance
      remain largely unknown. A deeper understanding of the complex pathophysiological
      cascade leading to aberrant connectivity in ASD can greatly benefit from the use
      of model organisms where individual pathophysiological or phenotypic components
      of ASD can be recreated and investigated via approaches that are either off
      limits or confounded by clinical heterogeneity. Despite some obvious limitations
      in reliably modeling the full phenotypic spectrum of a complex developmental
      disorder like ASD, mouse models have played a central role in advancing our basic
      mechanistic and molecular understanding of this syndrome. Recent progress in
      mouse brain connectivity mapping via resting-state fMRI (rsfMRI) offers the
      opportunity to generate and test mechanistic hypotheses about the elusive origin
      and significance of connectional aberrations observed in autism. Here we discuss
      recent progress toward this goal, and illustrate initial examples of how the
      approach can be employed to establish causal links between ASD-related mutations,
      developmental processes, and brain connectional architecture. As the spectrum of
      genetic and pathophysiological components of ASD modeled in the mouse is rapidly
      expanding, the use of rsfMRI can advance our mechanistic understanding of the
      origin and significance of the connectional alterations associated with autism,
      and their heterogeneous expression across patient cohorts.

PMID- 27891067
TI  - Are healthy smokers really healthy?
AB  - Cigarette smoke contains more than 4500 chemicals which have toxic, mutagenic and
      carcinogenic effects. Strong evidences have shown that current smokers take a
      significantly higher risk of cardiovascular diseases, chronic obstructive
      pulmonary disease (COPD) and lung cancer than nonsmokers. However, less attention
      has been paid to the smoking induced abnormalities in the individuals defined as
      healthy smokers who are normal with spirometry, radiographic images, routine
      physical exam and categorized as healthy control group in many researches.
      Actually, 'healthy smokers' are not healthy. This narrative review focuses on the
      smoking related pathophysiologic changes mainly in the respiratory system of
      healthy smokers, including inflammation and immune changes, genetic alterations,
      structural changes and pulmonary dysfunction.

PMID- 27891069
TI  - Automatic Segmentation of Human Cortical Layer-Complexes and Architectural Areas
      Using Ex vivo Diffusion MRI and Its Validation.
AB  - Recently, several magnetic resonance imaging contrast mechanisms have been shown
      to distinguish cortical substructure corresponding to selected cortical layers.
      Here, we investigate cortical layer and area differentiation by automatized
      unsupervised clustering of high-resolution diffusion MRI data. Several groups of
      adjacent layers could be distinguished in human primary motor and premotor
      cortex. We then used the signature of diffusion MRI signals along cortical depth
      as a criterion to detect area boundaries and find borders at which the signature
      changes abruptly. We validate our clustering results by histological analysis of
      the same tissue. These results confirm earlier studies which show that diffusion
      MRI can probe layer-specific intracortical fiber organization and, moreover,
      suggests that it contains enough information to automatically classify
      architecturally distinct cortical areas. We discuss the strengths and weaknesses
      of the automatic clustering approach and its appeal for MR-based cortical
      histology.

PMID- 27891071
TI  - Chronic Progressive Neurodegeneration in a Transgenic Mouse Model of Prion
      Disease.
AB  - Neurodegenerative diseases present pathologically with progressive structural
      destruction of neurons and accumulation of mis-folded proteins specific for each
      condition leading to brain atrophy and functional disability. Many animal models
      exert deposition of pathogenic proteins without an accompanying neurodegeneration
      pattern. The lack of a comprehensive model hinders efforts to develop treatment.
      We performed longitudinal quantification of cellular, neuronal and synaptic
      density, as well as of neurogenesis in brains of mice mimicking for genetic
      Creutzfeldt-Jacob disease as compared to age-matched wild-type mice. Mice
      exhibited a neurodegenerative process of progressive reduction in cortical
      neurons and synapses starting at age of 4-6 months, in accord with neurologic
      disability. This was accompanied by significant decrease in
      subventricular/subependymal zone neurogenesis. Although increased hippocampal
      neurogenesis was detected in mice, a neurodegenerative process of CA1 and CA3
      regions associated with impaired hippocampal-dependent memory function was
      observed. In conclusion, mice exhibit pathological neurodegeneration concomitant
      with neurological disease progression, indicating these mice can serve as a model
      for neurodegenerative diseases.

PMID- 27891072
TI  - Estimating Propensity Parameters Using Google PageRank and Genetic Algorithms.
AB  - Stochastic Boolean networks, or more generally, stochastic discrete networks, are
      an important class of computational models for molecular interaction networks.
      The stochasticity stems from the updating schedule. Standard updating schedules
      include the synchronous update, where all the nodes are updated at the same time,
      and the asynchronous update where a random node is updated at each time step. The
      former produces a deterministic dynamics while the latter a stochastic dynamics.
      A more general stochastic setting considers propensity parameters for updating
      each node. Stochastic Discrete Dynamical Systems (SDDS) are a modeling framework
      that considers two propensity parameters for updating each node and uses one when
      the update has a positive impact on the variable, that is, when the update causes
      the variable to increase its value, and uses the other when the update has a
      negative impact, that is, when the update causes it to decrease its value. This
      framework offers additional features for simulations but also adds a complexity
      in parameter estimation of the propensities. This paper presents a method for
      estimating the propensity parameters for SDDS. The method is based on adding
      noise to the system using the Google PageRank approach to make the system ergodic
      and thus guaranteeing the existence of a stationary distribution. Then with the
      use of a genetic algorithm, the propensity parameters are estimated.
      Approximation techniques that make the search algorithms efficient are also
      presented and Matlab/Octave code to test the algorithms are available at
      http://www.ms.uky.edu/~dmu228/GeneticAlg/Code.html.

PMID- 27891074
TI  - Interactive Sonification of Spontaneous Movement of Children-Cross-Modal Mapping
      and the Perception of Body Movement Qualities through Sound.
AB  - In this paper we present three studies focusing on the effect of different sound
      models in interactive sonification of bodily movement. We hypothesized that a
      sound model characterized by continuous smooth sounds would be associated with
      other movement characteristics than a model characterized by abrupt variation in
      amplitude and that these associations could be reflected in spontaneous movement
      characteristics. Three subsequent studies were conducted to investigate the
      relationship between properties of bodily movement and sound: (1) a motion
      capture experiment involving interactive sonification of a group of children
      spontaneously moving in a room, (2) an experiment involving perceptual ratings of
      sonified movement data and (3) an experiment involving matching between sonified
      movements and their visualizations in the form of abstract drawings. In (1) we
      used a system constituting of 17 IR cameras tracking passive reflective markers.
      The head positions in the horizontal plane of 3-4 children were simultaneously
      tracked and sonified, producing 3-4 sound sources spatially displayed through an
      8-channel loudspeaker system. We analyzed children's spontaneous movement in
      terms of energy-, smoothness- and directness-index. Despite large inter
      participant variability and group-specific effects caused by interaction among
      children when engaging in the spontaneous movement task, we found a small but
      significant effect of sound model. Results from (2) indicate that different sound
      models can be rated differently on a set of motion-related perceptual scales
      (e.g., expressivity and fluidity). Also, results imply that audio-only stimuli
      can evoke stronger perceived properties of movement (e.g., energetic, impulsive)
      than stimuli involving both audio and video representations. Findings in (3)
      suggest that sounds portraying bodily movement can be represented using abstract
      drawings in a meaningful way. We argue that the results from these studies
      support the existence of a cross-modal mapping of body motion qualities from
      bodily movement to sounds. Sound can be translated and understood from bodily
      motion, conveyed through sound visualizations in the shape of drawings and
      translated back from sound visualizations to audio. The work underlines the
      potential of using interactive sonification to communicate high-level features of
      human movement data.

PMID- 27891075
TI  - BACE1 RNAi Restores the Composition of Phosphatidylethanolamine-Derivates Related
      to Memory Improvement in Aged 3xTg-AD Mice.
AB  - beta-amyloid (Abeta) is produced by the beta-secretase 1 (BACE1)-mediated
      enzymatic cleavage of the amyloid precursor protein through the amyloidogenic
      pathway, making BACE1 a therapeutic target against Alzheimer's disease (AD).
      Alterations in lipid metabolism are a risk factor for AD by an unknown mechanism.
      The objective of this study was to determine the effect of RNA interference
      against BACE1 (shBACEmiR) on the phospholipid profile in hippocampal CA1 area in
      aged 3xTg-AD mice after 6 and 12 months of treatment compared to aged PS1KI mice.
      The shBACEmiR treatment induced cognitive function recovery and restored mainly
      the fatty acid composition of lysophosphatidylethanolamine and
      etherphosphatidylethanolamine, reduced the cPLA2's phosphorylation, down
      regulated the levels of arachidonic acid and COX2 in the hippocampi of 3xTg-AD
      mice. Together, our findings suggest, for the first time, that BACE1 silencing
      restores phospholipids composition which could favor the recovery of cellular
      homeostasis and cognitive function in the hippocampus of triple transgenic AD
      mice.

PMID- 27891076
TI  - Recombinant Adeno-Associated Virus Serotype 6 (rAAV6) Potently and Preferentially
      Transduces Rat Astrocytes In vitro and In vivo.
AB  - Recombinant adeno-associated virus vectors are an increasingly popular tool for
      gene delivery to the CNS because of their non-pathological nature, low
      immunogenicity, and ability to stably transduce dividing and non-dividing cells.
      One of the limitations of rAAVs is their preferential tropism for neuronal cells.
      Glial cells, specifically astrocytes, appear to be infected at low rates. To
      overcome this limitation, previous studies utilized rAAVs with astrocyte-specific
      promoters or assorted rAAV serotypes and pseudotypes with purported selectivity
      for astrocytes. Yet, the reported glial infection rates are not consistent from
      study to study. In the present work, we tested seven commercially available
      recombinant serotypes- rAAV1, 2, and 5 through 9, for their ability to transduce
      primary rat astrocytes [visualized via viral expression of green fluorescent
      protein (GFP)]. In cell cultures, rAAV6 consistently demonstrated the highest
      infection rates, while rAAV2 showed astrocytic transduction in some, but not all,
      of the tested viral batches. To verify that all rAAV constructs utilized by us
      were viable and effective, we confirmed high infectivity rates in retinal
      pigmented epithelial cells (ARPE-19), which are known to be transduced by
      numerous rAAV serotypes. Based on the in vitro results, we next tested the cell
      type tropism of rAAV6 and rAAV2 in vivo, which were both injected in the barrel
      cortex at approximately equal doses. Three weeks later, the brains were sectioned
      and immunostained for viral GFP and the neuronal marker NeuN or the astrocytic
      marker GFAP. We found that rAAV6 strongly and preferentially transduced
      astrocytes (>90% of cells in the virus-infected areas), but not neurons (~10%
      infection rate). On the contrary, rAAV2 preferentially infected neurons (~65%),
      but not astrocytes (~20%). Overall, our results suggest that rAAV6 can be used as
      a tool for manipulating gene expression (either delivery or knockdown) in rat
      astrocytes in vivo.

PMID- 27891070
TI  - Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity
      for Monoaminergic Multi-Target Drugs.
AB  - A large body of experimental and clinical evidence has strongly suggested that
      monoamines play an important role in regulating epileptogenesis, seizure
      susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in
      people with epilepsy (PWE). However, neither the relative significance of
      individual monoamines nor their interaction has yet been fully clarified due to
      the complexity of these neurotransmitter systems. In addition, epilepsy is
      diverse, with many different seizure types and epilepsy syndromes, and the role
      played by monoamines may vary from one condition to another. In this review, we
      will focus on the role of serotonin, dopamine, noradrenaline, histamine, and
      melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will
      be reviewed in consideration of the mutual relationship of monoamines with the
      other putative neurotransmitters. The complexity of epileptic pathogenesis may
      explain why the currently available drugs, developed according to the classic
      drug discovery paradigm of "one-molecule-one-target," have turned out to be
      effective only in a percentage of PWE. Although, no antiepileptic drugs currently
      target specifically monoaminergic systems, multi-target directed ligands acting
      on different monoaminergic proteins, present on both neurons and glia cells, may
      represent a new approach in the management of seizures, and their generation as
      well as comorbid neuropsychiatric disorders.

PMID- 27891078
TI  - Neural and Response Correlations to Complex Natural Sounds in the Auditory
      Midbrain.
AB  - How natural communication sounds are spatially represented across the inferior
      colliculus, the main center of convergence for auditory information in the
      midbrain, is not known. The neural representation of the acoustic stimuli results
      from the interplay of locally differing input and the organization of spectral
      and temporal neural preferences that change gradually across the nucleus. This
      raises the question of how similar the neural representation of the communication
      sounds is across these gradients of neural preferences, and whether it also
      changes gradually. Analyzed neural recordings were multi-unit cluster spike
      trains from guinea pigs presented with a spectrotemporally rich set of eleven
      species-specific communication sounds. Using cross-correlation, we analyzed the
      response similarity of spiking activity across a broad frequency range for
      neurons of similar and different frequency tuning. Furthermore, we separated the
      contribution of the stimulus to the correlations to investigate whether
      similarity is only attributable to the stimulus, or, whether interactions exist
      between the multi-unit clusters that lead to neural correlations and whether
      these follow the same representation as the response correlations. We found that
      similarity of responses is dependent on the neurons' spatial distance for
      similarly and differently frequency-tuned neurons, and that similarity decreases
      gradually with spatial distance. Significant neural correlations exist, and
      contribute to the total response similarity. Our findings suggest that for multi
      unit clusters in the mammalian inferior colliculus, the gradual response
      similarity with spatial distance to natural complex sounds is shaped by neural
      interactions and the gradual organization of neural preferences.

PMID- 27891073
TI  - A Hitchhiker's Guide to Functional Magnetic Resonance Imaging.
AB  - Functional Magnetic Resonance Imaging (fMRI) studies have become increasingly
      popular both with clinicians and researchers as they are capable of providing
      unique insights into brain functions. However, multiple technical considerations
      (ranging from specifics of paradigm design to imaging artifacts, complex protocol
      definition, and multitude of processing and methods of analysis, as well as
      intrinsic methodological limitations) must be considered and addressed in order
      to optimize fMRI analysis and to arrive at the most accurate and grounded
      interpretation of the data. In practice, the researcher/clinician must choose,
      from many available options, the most suitable software tool for each stage of
      the fMRI analysis pipeline. Herein we provide a straightforward guide designed to
      address, for each of the major stages, the techniques, and tools involved in the
      process. We have developed this guide both to help those new to the technique to
      overcome the most critical difficulties in its use, as well as to serve as a
      resource for the neuroimaging community.

PMID- 27891077
TI  - Presynaptic G Protein-Coupled Receptors: Gatekeepers of Addiction?
AB  - Drug abuse and addiction cause widespread social and public health problems, and
      the neurobiology underlying drug actions and drug use and abuse is an area of
      intensive research. Drugs of abuse alter synaptic transmission, and these actions
      contribute to acute intoxication as well as the chronic effects of abused
      substances. Transmission at most mammalian synapses involves neurotransmitter
      activation of two receptor subtypes, ligand-gated ion channels that mediate fast
      synaptic responses and G protein-coupled receptors (GPCRs) that have slower
      neuromodulatory actions. The GPCRs represent a large proportion of
      neurotransmitter receptors involved in almost all facets of nervous system
      function. In addition, these receptors are targets for many pharmacotherapeutic
      agents. Drugs of abuse directly or indirectly affect neuromodulation mediated by
      GPCRs, with important consequences for intoxication, drug taking and responses to
      prolonged drug exposure, withdrawal and addiction. Among the GPCRs are several
      subtypes involved in presynaptic inhibition, most of which are coupled to the
      Gi/o class of G protein. There is increasing evidence that these presynaptic Gi/o
      coupled GPCRs have important roles in the actions of drugs of abuse, as well as
      behaviors related to these drugs. This topic will be reviewed, with particular
      emphasis on receptors for three neurotransmitters, Dopamine (DA; D1- and D2-like
      receptors), Endocannabinoids (eCBs; CB1 receptors) and glutamate (group II
      metabotropic glutamate (mGlu) receptors). The focus is on recent evidence from
      laboratory animal models (and some evidence in humans) implicating these
      receptors in the acute and chronic effects of numerous abused drugs, as well as
      in the control of drug seeking and taking. The ability of drugs targeting these
      receptors to modify drug seeking behavior has raised the possibility of using
      compounds targeting these receptors for addiction pharmacotherapy. This topic is
      also discussed, with emphasis on development of mGlu2 positive allosteric
      modulators (PAMs).

PMID- 27891080
TI  - Enhanced Burst-Suppression and Disruption of Local Field Potential Synchrony in a
      Mouse Model of Focal Cortical Dysplasia Exhibiting Spike-Wave Seizures.
AB  - Focal cortical dysplasias (FCDs) are a common cause of brain seizures and are
      often associated with intractable epilepsy. Here we evaluated aberrant brain
      neurophysiology in an in vivo mouse model of FCD induced by neonatal freeze
      lesions (FLs) to the right cortical hemisphere (near S1). Linear multi-electrode
      arrays were used to record extracellular potentials from cortical and subcortical
      brain regions near the FL in anesthetized mice (5-13 months old) followed by 24 h
      cortical electroencephalogram (EEG) recordings. Results indicated that FL animals
      exhibit a high prevalence of spontaneous spike-wave discharges (SWDs),
      predominately during sleep (EEG), and an increase in the incidence of hyper
      excitable burst/suppression activity under general anesthesia (extracellular
      recordings, 0.5%-3.0% isoflurane). Brief periods of burst activity in the local
      field potential (LFP) typically presented as an arrhythmic pattern of increased
      theta-alpha spectral peaks (4-12 Hz) on a background of low-amplitude delta
      activity (1-4 Hz), were associated with an increase in spontaneous spiking of
      cortical neurons, and were highly synchronized in control animals across
      recording sites in both cortical and subcortical layers (average cross
      correlation values ranging from +0.73 to +1.0) with minimal phase shift between
      electrodes. However, in FL animals, cortical vs. subcortical burst activity was
      strongly out of phase with significantly lower cross-correlation values compared
      to controls (average values of -0.1 to +0.5, P < 0.05 between groups). In
      particular, a marked reduction in the level of synchronous burst activity was
      observed, the closer the recording electrodes were to the malformation (Pearson's
      Correlation = 0.525, P < 0.05). In a subset of FL animals (3/9), burst activity
      also included a spike or spike-wave pattern similar to the SWDs observed in
      unanesthetized animals. In summary, neonatal FLs increased the hyperexcitable
      pattern of burst activity induced by anesthesia and disrupted field potential
      synchrony between cortical and subcortical brain regions near the site of the
      cortical malformation. Monitoring the altered electrophysiology of burst activity
      under general anesthesia with multi-dimensional micro-electrode arrays may serve
      to define distinct neurophysiological biomarkers of epileptogenesis in human
      brain and improve techniques for surgical resection of epileptogenic malformed
      brain tissue.

PMID- 27891081
TI  - The Brain of the Archerfish Toxotes chatareus: A Nissl-Based Neuroanatomical
      Atlas and Catecholaminergic/Cholinergic Systems.
AB  - Over recent years, the seven-spot archerfish (Toxotes chatareus) has emerged as a
      new model for studies in visual and behavioral neuroscience thanks to its unique
      hunting strategy. Its natural ability to spit at insects outside of water can be
      used in the laboratory for well controlled behavioral experiments where the fish
      is trained to aim at targets on a screen. The need for a documentation of the
      neuroanatomy of this animal became critical as more research groups use it as a
      model. Here we present an atlas of adult T. chatareus specimens caught in the
      wild in South East Asia. The atlas shows representative sections of the brain and
      specific structures revealed by a classic Nissl staining as well as corresponding
      schematic drawings. Additional immunostainings for catecholaminergic and
      cholinergic systems were conducted to corroborate the identification of certain
      nuclei and the data of a whole brain scanner is available online. We describe the
      general features of the archerfish brain as well as its specificities, especially
      for the visual system and compare the neuroanatomy of the archerfish with other
      teleosts. This atlas of the archerfish brain shows all levels of the neuraxis and
      intends to provide a solid basis for further neuroscientific research on T.
      chatareus, in particular electrophysiological studies.

PMID- 27891082
TI  - Reward and Behavioral Factors Contributing to the Tonic Activity of Monkey
      Pedunculopontine Tegmental Nucleus Neurons during Saccade Tasks.
AB  - The pedunculopontine tegmental nucleus (PPTg) in the brainstem plays a role in
      controlling reinforcement learning and executing conditioned behavior. We
      previously examined the activity of PPTg neurons in monkeys during a reward
      conditioned, visually guided saccade task, and reported that a population of
      these neurons exhibited tonic responses throughout the task period. These tonic
      responses might depend on prediction of the upcoming reward, successful execution
      of the task, or both. Here, we sought to further distinguish these factors and to
      investigate how each contributes to the tonic neuronal activity of the PPTg. In
      our normal visually guided saccade task, the monkey initially fixated on the
      central fixation target (FT), then made saccades to the peripheral saccade target
      and received a juice reward after the saccade target disappeared. Most of the
      tonic activity terminated shortly after the reward delivery, when the monkey
      broke fixation. To distinguish between reward and behavioral epochs, we then
      changed the task sequence for a block of trials, such that the saccade target
      remained visible after the reward delivery. Under these visible conditions, the
      monkeys tended to continue fixating on the saccade target even after the reward
      delivery. Therefore, the prediction of the upcoming reward and the end of an
      individual trial were separated in time. Regardless of the task conditions, half
      of the tonically active PPTg neurons terminated their activity around the time of
      the reward delivery, consistent with the view that PPTg neurons might send reward
      prediction signals until the time of reward delivery, which is essential for
      computing reward prediction error in reinforcement learning. On the other hand,
      the other half of the tonically active PPTg neurons changed their activity
      dependent on the task condition. In the normal condition, the tonic responses
      terminated around the time of the reward delivery, while in the visible
      condition, the activity continued until the disappearance of the saccade target
      (ST) after reward delivery. Thus, for these neurons, the tonic activity might be
      related to maintaining attention to complete fixation behavior. These results
      suggest that, in addition to the reward value information, some PPTg neurons
      might contribute to the execution of conditioned task behavior.

PMID- 27891083
TI  - Toward a P300 Based Brain-Computer Interface for Aphasia Rehabilitation after
      Stroke: Presentation of Theoretical Considerations and a Pilot Feasibility Study.
AB  - People with post-stroke motor aphasia know what they would like to say but cannot
      express it through motor pathways due to disruption of cortical circuits. We
      present a theoretical background for our hypothesized connection between
      attention and aphasia rehabilitation and suggest why in this context, Brain
      Computer Interface (BCI) use might be beneficial for patients diagnosed with
      aphasia. Not only could BCI technology provide a communication tool, it might
      support neuronal plasticity by activating language circuits and thereby boost
      aphasia recovery. However, stroke may lead to heterogeneous symptoms that might
      hinder BCI use, which is why the feasibility of this approach needs to be
      investigated first. In this pilot study, we included five participants diagnosed
      with post-stroke aphasia. Four participants were initially unable to use the
      visual P300 speller paradigm. By adjusting the paradigm to their needs,
      participants could successfully learn to use the speller for communication with
      accuracies up to 100%. We describe necessary adjustments to the paradigm and
      present future steps to investigate further this approach.

PMID- 27891079
TI  - Contribution of TMS and rTMS in the Understanding of the Pathophysiology and in
      the Treatment of Dystonia.
AB  - Dystonias represent a heterogeneous group of movement disorders responsible for
      sustained muscle contraction, abnormal postures, and muscle twists. It can affect
      focal or segmental body parts or be generalized. Primary dystonia is the most
      common form of dystonia but it can also be secondary to metabolic or structural
      dysfunction, the consequence of a drug's side-effect or of genetic origin. The
      pathophysiology is still not elucidated. Based on lesion studies, dystonia has
      been regarded as a pure motor dysfunction of the basal ganglia loop. However,
      basal ganglia lesions do not consistently produce dystonia and lesions outside
      basal ganglia can lead to dystonia; mild sensory abnormalities have been reported
      in the dystonic limb and imaging studies have shown involvement of multiple other
      brain regions including the cerebellum and the cerebral motor, premotor and
      sensorimotor cortices. Transcranial magnetic stimulation (TMS) is a non-invasive
      technique of brain stimulation with a magnetic field applied over the cortex
      allowing investigation of cortical excitability. Hyperexcitability of
      contralateral motor cortex has been suggested to be the trigger of focal
      dystonia. High or low frequency repetitive TMS (rTMS) can induce excitatory or
      inhibitory lasting effects beyond the time of stimulation and protocols have been
      developed having either a positive or a negative effect on cortical excitability
      and associated with prevention of cell death, gamma-aminobutyric acid (GABA)
      interneurons mediated inhibition and brain-derived neurotrophic factor
      modulation. rTMS studies as a therapeutic strategy of dystonia have been
      conducted to modulate the cerebral areas involved in the disease. Especially,
      when applied on the contralateral (pre)-motor cortex or supplementary motor area
      of brains of small cohorts of dystonic patients, rTMS has shown a beneficial
      transient clinical effect in association with restrained motor cortex
      excitability. TMS is currently a valuable tool to improve our understanding of
      the pathophysiology of dystonia but large controlled studies using sham
      stimulation are still necessary to delineate the place of rTMS in the therapeutic
      strategy of dystonia. In this review, we will focus successively on the use of
      TMS as a tool to better understand pathophysiology, and the use of rTMS as a
      therapeutic strategy.

PMID- 27891084
TI  - Differential Effects of Visual-Acoustic Biofeedback Intervention for Residual
      Speech Errors.
AB  - Recent evidence suggests that the incorporation of visual biofeedback
      technologies may enhance response to treatment in individuals with residual
      speech errors. However, there is a need for controlled research systematically
      comparing biofeedback versus non-biofeedback intervention approaches. This study
      implemented a single-subject experimental design with a crossover component to
      investigate the relative efficacy of visual-acoustic biofeedback and traditional
      articulatory treatment for residual rhotic errors. Eleven child/adolescent
      participants received ten sessions of visual-acoustic biofeedback and 10 sessions
      of traditional treatment, with the order of biofeedback and traditional phases
      counterbalanced across participants. Probe measures eliciting untreated rhotic
      words were administered in at least three sessions prior to the start of
      treatment (baseline), between the two treatment phases (midpoint), and after
      treatment ended (maintenance), as well as before and after each treatment
      session. Perceptual accuracy of rhotic production was assessed by outside
      listeners in a blinded, randomized fashion. Results were analyzed using a
      combination of visual inspection of treatment trajectories, individual effect
      sizes, and logistic mixed-effects regression. Effect sizes and visual inspection
      revealed that participants could be divided into categories of strong responders
      (n = 4), mixed/moderate responders (n = 3), and non-responders (n = 4).
      Individual results did not reveal a reliable pattern of stronger performance in
      biofeedback versus traditional blocks, or vice versa. Moreover, biofeedback
      versus traditional treatment was not a significant predictor of accuracy in the
      logistic mixed-effects model examining all within-treatment word probes. However,
      the interaction between treatment condition and treatment order was significant:
      biofeedback was more effective than traditional treatment in the first phase of
      treatment, and traditional treatment was more effective than biofeedback in the
      second phase. This is consistent with existing theory and data suggesting that
      detailed knowledge of performance feedback is most effective in the early stages
      of motor learning. Further research is needed to confirm that an initial phase of
      biofeedback has a facilitative effect, and to determine the optimal duration of
      biofeedback treatment. In addition, there is a strong need for correlational
      studies to examine which individuals with residual speech errors are most likely
      to respond to treatment.

PMID- 27891085
TI  - Pain Perception Can Be Modulated by Mindfulness Training: A Resting-State fMRI
      Study.
AB  - The multi-dimensional nature of pain renders difficult a holistic understanding
      of it. The conceptual framework of pain is said to be cognitive-evaluative, in
      addition to being sensory-discriminative and affective-motivational. To compare
      participants' brain-behavior response before and after a 6-week mindfulness-based
      stress reduction training course on mindfulness in relation to pain modulation,
      three questionnaires (the Dallas Pain Questionnaire, Short Form McGill Pain
      Questionnaire-SFMPQ, and Kentucky Inventory of Mindfulness) as well as resting
      state functional magnetic resonance imaging were administered to participants,
      divided into a pain-afflicted group (N = 18) and a control group (N = 16). Our
      results showed that the pain-afflicted group experienced significantly less pain
      after the mindfulness treatment than before, as measured by the SFMPQ. In
      conjunction, an increased connection from the anterior insular cortex (AIC) to
      the dorsal anterior midcingulate cortex (daMCC) was observed in the post-training
      pain-afflicted group and a significant correlation was found between AIC-daMCC
      connectivity and SFMPQ scores. The results suggest that mindfulness training can
      modulate the brain network dynamics underlying the subjective experience of pain.

PMID- 27891087
TI  - A Monte Carlo Evaluation of Weighted Community Detection Algorithms.
AB  - The past decade has been marked with a proliferation of community detection
      algorithms that aim to organize nodes (e.g., individuals, brain regions,
      variables) into modular structures that indicate subgroups, clusters, or
      communities. Motivated by the emergence of big data across many fields of
      inquiry, these methodological developments have primarily focused on the
      detection of communities of nodes from matrices that are very large. However, it
      remains unknown if the algorithms can reliably detect communities in smaller
      graph sizes (i.e., 1000 nodes and fewer) which are commonly used in brain
      research. More importantly, these algorithms have predominantly been tested only
      on binary or sparse count matrices and it remains unclear the degree to which the
      algorithms can recover community structure for different types of matrices, such
      as the often used cross-correlation matrices representing functional connectivity
      across predefined brain regions. Of the publicly available approaches for
      weighted graphs that can detect communities in graph sizes of at least 1000,
      prior research has demonstrated that Newman's spectral approach (i.e., Leading
      Eigenvalue), Walktrap, Fast Modularity, the Louvain method (i.e., multilevel
      community method), Label Propagation, and Infomap all recover communities
      exceptionally well in certain circumstances. The purpose of the present Monte
      Carlo simulation study is to test these methods across a large number of
      conditions, including varied graph sizes and types of matrix (sparse count,
      correlation, and reflected Euclidean distance), to identify which algorithm is
      optimal for specific types of data matrices. The results indicate that when the
      data are in the form of sparse count networks (such as those seen in diffusion
      tensor imaging), Label Propagation and Walktrap surfaced as the most reliable
      methods for community detection. For dense, weighted networks such as correlation
      matrices capturing functional connectivity, Walktrap consistently outperformed
      the other approaches for recovering communities.

PMID- 27891086
TI  - Circuits Regulating Pleasure and Happiness-Mechanisms of Depression.
AB  - According to our model of the regulation of appetitive-searching vs. distress
      avoiding behaviors, the motivation to display these essential conducts is
      regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits,
      including the core and the shell parts of the nucleus accumbens, respectively. An
      entire series of basal ganglia, running from the caudate nucleus on one side, to
      the centromedial amygdala on the other side, controls the intensity of these
      reward-seeking and misery-fleeing behaviors by stimulating the activity of the
      (pre)frontal and limbic cortices. Hyperactive motivation to display behavior that
      potentially results in reward induces feelings of hankering (relief leads to
      pleasure). Hyperactive motivation to exhibit behavior related to avoidance of
      misery results in dysphoria (relief leads to happiness). These two systems
      collaborate in a reciprocal fashion. In clinical depression, a mismatch exists
      between the activities of these two circuits: the balance is shifted to the
      misery-avoiding side. Five theories have been developed to explain the mechanism
      of depressive mood disorders, including the monoamine, biorhythm, neuro
      endocrine, neuro-immune, and kindling/neuroplasticity theories. This paper
      describes these theories in relationship to the model (described above) of the
      regulation of reward-seeking vs. misery-avoiding behaviors. Chronic stress that
      leads to structural changes may induce the mismatch between the two systems. This
      mismatch leads to lack of pleasure, low energy, and indecisiveness, on one hand,
      and dysphoria, continuous worrying, and negative expectations on the other hand.
      The neuroplastic effects of monoamines, cortisol, and cytokines may mediate the
      induction of these structural alterations. Long-term exposure to stressful
      situations (particularly experienced during childhood) may lead to increased
      susceptibility for developing this condition. This hypothesis opens up the
      possibility of treating depression with psychotherapy. Genetic and other
      biological factors (toxic, infectious, or traumatic) may increase sensitivity to
      the induction of relevant neuroplastic changes. Reversal or compensation of these
      neuroplastic adjustments may explain the effects of biological therapies in
      treating depression.

PMID- 27891088
TI  - An EMG Interface for the Control of Motion and Compliance of a Supernumerary
      Robotic Finger.
AB  - In this paper, we propose a novel electromyographic (EMG) control interface to
      control motion and joints compliance of a supernumerary robotic finger. The
      supernumerary robotic fingers are a recently introduced class of wearable
      robotics that provides users additional robotic limbs in order to compensate or
      augment the existing abilities of natural limbs without substituting them. Since
      supernumerary robotic fingers are supposed to closely interact and perform
      actions in synergy with the human limbs, the control principles of extra finger
      should have similar behavior as human's ones including the ability of regulating
      the compliance. So that, it is important to propose a control interface and to
      consider the actuators and sensing capabilities of the robotic extra finger
      compatible to implement stiffness regulation control techniques. We propose EMG
      interface and a control approach to regulate the compliance of the device through
      servo actuators. In particular, we use a commercial EMG armband for gesture
      recognition to be associated with the motion control of the robotic device and
      surface one channel EMG electrodes interface to regulate the compliance of the
      robotic device. We also present an updated version of a robotic extra finger
      where the adduction/abduction motion is realized through ball bearing and spur
      gears mechanism. We have validated the proposed interface with two sets of
      experiments related to compensation and augmentation. In the first set of
      experiments, different bimanual tasks have been performed with the help of the
      robotic device and simulating a paretic hand since this novel wearable system can
      be used to compensate the missing grasping abilities in chronic stroke patients.
      In the second set, the robotic extra finger is used to enlarge the workspace and
      manipulation capability of healthy hands. In both sets, the same EMG control
      interface has been used. The obtained results demonstrate that the proposed
      control interface is intuitive and can successfully be used, not only to control
      the motion of a supernumerary robotic finger but also to regulate its compliance.
      The proposed approach can be exploited also for the control of different wearable
      devices that has to actively cooperate with the human limbs.

PMID- 27891090
TI  - Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in
      Parkinson's Disease.
AB  - The recent application of graph theory to brain networks promises to shed light
      on complex diseases such as Parkinson's disease (PD). This study aimed to
      investigate functional changes in sensorimotor and cognitive networks in
      Parkinsonian patients, with a focus on inter- and intra-connectivity organization
      in the disease-associated nodal and hub regions using the graph theoretical
      analyses. Resting-state functional MRI data of a total of 65 participants,
      including 23 healthy controls (HCs) and 42 patients, were investigated in 120
      nodes for local efficiency, betweenness centrality, and degree. Hub regions were
      identified in the HC and patient groups. We found nodal and hub changes in
      patients compared with HCs, including the right pre-supplementary motor area
      (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral
      prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions
      within the sensorimotor network (i.e., right pre-SMA and right mid-insula)
      displayed weakened connectivity, with the former node associated with more severe
      bradykinesia, and impaired integration with default mode network regions. The
      left mid-insula also lost its hub properties in patients. Within the executive
      networks, the left anterior insular cortex lost its hub properties in patients,
      while a new hub region was identified in the right caudate nucleus, paralleled by
      an increased level of inter- and intra-connectivity in the bilateral DLPFC
      possibly representing compensatory mechanisms. These findings highlight the
      diffuse changes in nodal organization and regional hub disruption accounting for
      the distributed abnormalities across brain networks and the clinical
      manifestations of PD.

PMID- 27891089
TI  - Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in
      Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial.
AB  - : Alzheimer's disease (AD) is associated with severe cognitive impairments as
      well as some metabolic defects. Scant studies in animal models indicate a link
      between probiotics and cognitive function. This randomized, double-blind, and
      controlled clinical trial was conducted among 60 AD patients to assess the
      effects of probiotic supplementation on cognitive function and metabolic status.
      The patients were randomly divided into two groups (n = 30 in each group)
      treating with either milk (control group) or a mixture of probiotics (probiotic
      group). The probiotic supplemented group took 200 ml/day probiotic milk
      containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium
      bifidum, and Lactobacillus fermentum (2 * 109 CFU/g for each) for 12 weeks. Mini
      mental state examination (MMSE) score was recorded in all subjects before and
      after the treatment. Pre- and post-treatment fasting blood samples were obtained
      to determine the related markers. After 12 weeks intervention, compared with the
      control group (-5.03% +/- 3.00), the probiotic treated (+27.90% +/- 8.07)
      patients showed a significant improvement in the MMSE score (P <0.001). In
      addition, changes in plasma malondialdehyde (-22.01% +/- 4.84 vs. +2.67% +/- 3.86
      MUmol/L, P <0.001), serum high-sensitivity C-reactive protein (-17.61% +/- 3.70
      vs. +45.26% +/- 3.50 MUg/mL, P <0.001), homeostasis model of assessment-estimated
      insulin resistance (+28.84% +/- 13.34 vs. +76.95% +/- 24.60, P = 0.002), Beta
      cell function (+3.45% +/- 10.91 vs. +75.62% +/- 23.18, P = 0.001), serum
      triglycerides (-20.29% +/- 4.49 vs. -0.16% +/- 5.24 mg/dL, P = 0.003), and
      quantitative insulin sensitivity check index (-1.83 +/- 1.26 vs. -4.66 +/- 1.70,
      P = 0.006) in the probiotic group were significantly varied compared to the
      control group. We found that the probiotic treatment had no considerable effect
      on other biomarkers of oxidative stress and inflammation, fasting plasma glucose,
      and other lipid profiles. Overall, the current study demonstrated that probiotic
      consumption for 12 weeks positively affects cognitive function and some metabolic
      statuses in the AD patients. CLINICAL TRIAL REGISTRATION: http://www.irct.ir/,
      IRCT201511305623N60.

PMID- 27891091
TI  - Amyloid Plaques in Retina for Diagnosis in Alzheimer's Patients: a Meta-Analysis.
AB  - Background: Detection of retinal beta-amyloid (Abeta) peptide accumulation is a
      novel diagnostic method for Alzheimer's disease (AD), but there is, as yet, no
      conclusive evidence of its accuracy. Aim: To identify the diagnostic accuracy of
      pathological retinal Abeta detection for AD by a meta-analytic approach. Methods:
      Electronic and reference searches were conducted to identify studies related to
      the diagnostic effects of retinal Abeta detection in AD that met pre-defined
      inclusion criteria. The QUADAS-2 tool was employed to assess the risk of bias,
      and Review Manager plus the Open Meta-Analyst were used to perform the data
      analysis. Results: From 493 unduplicated reports, five studies with small sample
      sizes were included in this review. Six staining methods were employed. The
      eligible studies showed extremely broad ranges of sensitivity (0-1.00) and
      specificity (0.50-1.00) with substantial heterogeneity. The estimates of positive
      likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio
      (DOR) were also extremely varied (from 0.71 to 11.57 for PLR, from 0.04 to 1.11
      for NLR, and from 0.69 to 297.00 for DOR). Conclusions: The limited number of
      eligible studies and their methodological heterogeneity make it impossible to
      come to a conclusion whether pathological retinal Abeta detection is an effective
      diagnostic tool for AD. More studies, especially large surveys investigating
      retina Abeta load with quantitative methods among consecutive or random samples,
      are needed to determine the accuracy of Abeta detection for diagnosing AD.

PMID- 27891092
TI  - Dihydrotanshinone I Attenuates Atherosclerosis in ApoE-Deficient Mice: Role of
      NOX4/NF-kappaB Mediated Lectin-Like Oxidized LDL Receptor-1 (LOX-1) of the
      Endothelium.
AB  - Dihydrotanshinone I (DHT) is a natural compound extracted from Salvia
      miltiorrhiza Bunge which has been widely used for treating cardiovascular
      diseases. However, its role in atherosclerosis remains unclear. In this study,
      the effect of DHT on atherosclerosis were investigated using apolipoprotein E
      deficient (ApoE-/-) mice and endothelial cells. In lipopolysaccharide (LPS)
      stimulated human umbilical vein endothelial cells (HUVECs), DHT (10 nM) decreased
      lectin-like ox-LDL receptor-1 (LOX-1) and NADPH oxidase 4 (NOX4) expression,
      reactive oxygen species (ROS) production, NF-kappaB nuclear translocation, ox-LDL
      endocytosis and monocytes adhesion. Silence NOX4 inhibited LPS-induced LOX-1
      expression, NF-kappaB nuclear translocation, ox-LDL endocytosis and monocytes
      adhesion. In ApoE-/- mice fed with an atherogenic diet, DHT (10 and 25 mg kg-1)
      significantly attenuated atherosclerotic plaque formation, altered serum lipid
      profile, decreased oxidative stress and shrunk necrotic core areas. The enhanced
      expression of LOX-1, NOX4, and NF-kappaB in aorta was also dramatically inhibited
      by DHT. In conclusion, these results suggested that DHT showed anti
      atherosclerotic activity through inhibition of LOX-1 mediated by NOX4/NF-kappaB
      signaling pathways both in vitro and in vivo. This finding suggested that DHT
      might be used as a potential vascular protective candidate for the treatment of
      atherosclerosis.

PMID- 27891093
TI  - Targeting Strategies for Renal Cell Carcinoma: From Renal Cancer Cells to Renal
      Cancer Stem Cells.
AB  - Renal cell carcinoma (RCC) is a common form of urologic tumor that originates
      from the highly heterogeneous epithelium of renal tubules. Over the last decade,
      targeting therapies to renal cancer cells have transformed clinical care for RCC.
      Recently, it was proposed that renal cancer stem cells (CSCs) isolated from renal
      carcinomas were responsible for driving tumor growth and resistance to
      conventional chemotherapy and radiotherapy, according to the theory of CSCs; this
      has provided the rationale for therapies targeting this aggressive cell
      population. Precise identification of renal CSC populations and the complete cell
      hierarchy will accurately inform characterization of disease subtypes. This will
      ultimately contribute to more personalized and targeted therapies. Here, we
      summarize potential targeting strategies for renal cancer cells and renal CSCs,
      including tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors
      (mTOR), interleukins, CSC marker inhibitors, bone morphogenetic protein-2,
      antibody drug conjugates, and nanomedicine. In conclusion, targeting therapies
      for RCC represent new directions for exploration and clinical investigation and
      they plant a seed of hope for advanced clinical care.

PMID- 27891094
TI  - Anti-Acne Activity of Italian Medicinal Plants Used for Skin Infection.
AB  - Propionibacterium acnes is implicated in the pathogenesis of acne vulgaris, which
      impacts >85% of teenagers. Novel therapies are in high demand and an
      ethnopharmacological approach to discovering new plant sources of anti-acne
      therapeutics could contribute to filling this void in effective therapies. The
      aims of our study were two-fold: (1) To determine if species identified in
      ethnopharmacological field studies as having traditional uses for skin and soft
      tissue infection (SSTI) exhibit significantly more activity against P. acnes than
      species with no such reported use; and (2) Chemically characterize active
      extracts and assess their suitability for future investigation. Extracts of
      Italian medicinal (for acne and other skin infection) and randomly collected
      plants and fungi were screened for growth-inhibitory and anti-biofilm activity in
      P. acnes using broth microdilution methods. Bioactive extracts were chemically
      characterized by HPLC and examined for cytotoxicity against human keratinocytes
      (HaCaTs). Following evaluation of 157 extracts from 10 fungi and 58 plants, we
      identified crude extracts from seven species exhibiting growth inhibitory
      activity (MICs 64-256 MUg mL-1). All active extracts were examined for
      cytotoxicity against HaCaTs; extracts from one fungal and one plant species were
      toxic (IC50 256 MUg mL-1). HPLC analysis with chemical standards revealed many of
      these extracts contained chlorogenic acid, p-coumaric acid, ellagic acid, gallic
      acid, and tannic acid. In conclusion, species used in traditional medicine for
      the skin exhibited significantly greater (p < 0.05) growth inhibitory and biofilm
      eradication activity than random species, supporting the validity of an
      ethnobotanical approach to identifying new therapeutics. The anti-acne activity
      of three extracts is reported for the first time: Vitis vinifera leaves,
      Asphodelus microcarpus leaves, and Vicia sativa aerial parts.

PMID- 27891095
TI  - Differential RNA Expression Profile of Skeletal Muscle Induced by Experimental
      Autoimmune Myasthenia Gravis in Rats.
AB  - The differential susceptibility of skeletal muscle by myasthenia gravis (MG) is
      not well understood. We utilized RNA expression profiling of extraocular muscle
      (EOM), diaphragm (DIA), and extensor digitorum (EDL) of rats with experimental
      autoimmune MG (EAMG) to evaluate the hypothesis that muscles respond
      differentially to injury produced by EAMG. EAMG was induced in female Lewis rats
      by immunization with acetylcholine receptor purified from the electric organ of
      the Torpedo. Six weeks later after rats had developed weakness and serum
      antibodies directed against the AChR, animals underwent euthanasia and RNA
      profiling performed on DIA, EDL, and EOM. Profiling results were validated by
      qPCR. Across the three muscles between the experiment and control groups, 359
      probes (1.16%) with greater than 2-fold changes in expression in 7 of 9 series
      pairwise comparisons from 31,090 probes were identified with approximately two
      thirds being increased. The three muscles shared 16 genes with increased
      expression and 6 reduced expression. Functional annotation demonstrated that
      these common expression changes fell predominantly into categories of metabolism,
      stress response, and signaling. Evaluation of specific gene function indicated
      that EAMG led to a change to oxidative metabolism. Genes related to muscle
      regeneration and suppression of immune response were activated. Evidence of a
      differential immune response among muscles was not evident. Each muscle had a
      distinct RNA profile but with commonality in gene categories expressed that are
      focused on muscle repair, moderation of inflammation, and oxidative metabolism.

PMID- 27891096
TI  - Systematic Characterization of Dynamic Parameters of Intracellular Calcium
      Signals.
AB  - Dynamic processes, such as intracellular calcium signaling, are hallmark of
      cellular biology. As real-time imaging modalities become widespread, a need for
      analytical tools to reliably characterize time-series data without prior
      knowledge of the nature of the recordings becomes more pressing. The goal of this
      study is to develop a signal-processing algorithm for MATLAB that autonomously
      computes the parameters characterizing prominent single transient responses (TR)
      and/or multi-peaks responses (MPR). The algorithm corrects for signal
      contamination and decomposes experimental recordings into contributions from
      drift, TRs, and MPRs. It subsequently provides numerical estimates for the
      following parameters: time of onset after stimulus application, activation time
      (time for signal to increase from 10 to 90% of peak), and amplitude of response.
      It also provides characterization of the (i) TRs by quantifying their area under
      the curve (AUC), response duration (time between 1/2 amplitude on ascent and
      descent of the transient), and decay constant of the exponential decay region of
      the deactivation phase of the response, and (ii) MPRs by quantifying the number
      of peaks, mean peak magnitude, mean periodicity, standard deviation of
      periodicity, oscillatory persistence (time between first and last discernable
      peak), and duty cycle (fraction of period during which system is active) for all
      the peaks in the signal, as well as coherent oscillations (i.e., deterministic
      spikes). We demonstrate that the signal detection performance of this algorithm
      is in agreement with user-mediated detection and that parameter estimates
      obtained manually and algorithmically are correlated. We then apply this
      algorithm to study how metabolic acidosis affects purinergic (P2) receptor
      mediated calcium signaling in osteoclast precursor cells. Our results reveal that
      acidosis significantly attenuates the amplitude and AUC calcium responses at high
      ATP concentrations. Collectively, our data validated this algorithm as a general
      framework for comprehensively analyzing dynamic time-series.

PMID- 27891098
TI  - Deceptive Manipulation of Competitive Starting Strategies Influences Subsequent
      Pacing, Physiological Status, and Perceptual Responses during Cycling Time
      Trials.
AB  - Little is currently known regarding competitor influence on pacing at the start
      of an event and in particular the subsequent effect on the remaining distance.
      The purpose of the present study was to investigate the influence of starting
      pace on the physiological and psychological responses during cycling time trials
      (TT) utilizing an innovative approach allowing pace to be accurately and
      dynamically replicated, as well as deceptively manipulated. Ten competitive male
      cyclists completed five 16.1 km TT, two baseline trials performed alone (BLs),
      and three with a simulated, dynamic avatar of which they were to match the pace
      of for the initial 4 km. The avatar represented either the cyclist's fastest BL
      performance (NORM), 105% (FAST), or 95% (SLOW), of fastest BL performance (FBL).
      Physiological and psychological responses were measured every quartile of the TT.
      Despite manipulating a starting speed of +/- 5% of fastest previous performance,
      there was no effect on overall 16.1 km TT performance. Manipulated starting
      strategies did however evoke different physiological and perceptual responses.
      Whole trial differences found that SLOW produced lower HR, VO2, BLa and RPE than
      FBL (p <= 0.03) and higher SE than FAST (p <= 0.03). Additionally, FAST had
      greater internal attention than NORM (p < 0.04). Over time all psychological and
      physiological variables had a significant condition * quartile interaction in the
      initial or second quartile mediated by the prescribed starting strategies.
      Furthermore, RPE, affect, and internal attention remained elevated throughout
      FAST despite an attenuation in pace during self-selection of pace. There were no
      differences in performance time when manipulating a 16.1 km cycling TT starting
      strategy. A slow start, encouraged greater positive perceptions, and less
      negative physiological consequences than a faster start, and produces no
      impairment to performance time. It would therefore be considered an advantage in
      a non-drafting event, not to follow pace of fellow, superior competitors at the
      start of an event but perform a more negative pacing strategy, with the potential
      for a greater speed increase against opponents in the latter stages.

PMID- 27891097
TI  - Molecular Characterization of Aquaporin 1 and Aquaporin 3 from the Gills of the
      African Lungfish, Protopterus annectens, and Changes in Their Branchial mRNA
      Expression Levels and Protein Abundance during Three Phases of Aestivation.
AB  - African lungfishes can undergo long periods of aestivation on land during
      drought. During aestivation, lungfishes are confronted with desiccation and
      dehydration, and their gills become non-functional and covered with a thick layer
      of dried mucus. Aquaporins (Aqps) are a superfamily of integral membrane proteins
      which generally facilitate the permeation of water through plasma membranes. This
      study aimed to obtain the complete cDNA coding sequences of aqp1 and aqp3 from
      the gills of Protopterus annectens, and to determine their branchial mRNA and
      protein expression levels during the induction, maintenance and arousal phases of
      aestivation. Dendrogramic analyses of the deduced Aqp1 and Aqp3 amino acid
      sequences of P. annectens revealed their close relationships with those of
      Latimeria chalumnae and tetrapods. During the induction phase, there were
      significant decreases in the transcript levels of aqp1 and aqp3 in the gills of
      P. annectens, but the branchial Aqp1 and Aqp3 protein abundance remained
      unchanged. As changes in transcription might precede changes in translation, this
      could be regarded as an adaptive response to decrease the protein abundance of
      Aqp1 and Aqp3 in the subsequent maintenance phase of aestivation. As expected,
      the branchial transcript levels and protein abundance of aqp1/Aqp1 and aqp3/Aqp3
      were significantly down-regulated during the maintenance phase, probably
      attributable to the shutdown of branchial functions and the cessation of volume
      regulation of branchial epithelial cells. Additionally, these changes could
      reduce the loss of water through branchial epithelial surfaces, supplementing the
      anti-desiccating property of the dried mucus. Upon arousal, it was essential for
      the lungfish to restore branchial functions. Indeed, the protein abundance of
      Aqp1 recovered partially, with complete recovery of mRNA expression level and
      protein abundance of Aqp3, in the gills of P. annectens after 3 days of arousal.
      These results provide insights into how P. annectens regulates branchial Aqp
      expression to cope with desiccation and rehydration during different phases of
      aestivation.

PMID- 27891099
TI  - Reduced Phrenic Motoneuron Recruitment during Sustained Inspiratory Threshold
      Loading Compared to Single-Breath Loading: A Twitch Interpolation Study.
AB  - In humans, inspiratory constraints engage cortical networks involving the
      supplementary motor area. Functional magnetic resonance imaging (fMRI) shows that
      the spread and intensity of the corresponding respiratory-related cortical
      activation dramatically decrease when a discrete load becomes sustained. This has
      been interpreted as reflecting motor cortical reorganization and automatisation,
      but could proceed from sensory and/or affective habituation. To corroborate the
      existence of motor reorganization between single-breath and sustained inspiratory
      loading (namely changes in motor neurones recruitment), we conducted a diaphragm
      twitch interpolation study based on the hypothesis that motor reorganization
      should result in changes in the twitch interpolation slope. Fourteen healthy
      subjects (age: 21-40 years) were studied. Bilateral phrenic stimulation was
      delivered at rest, upon prepared and targeted voluntary inspiratory efforts
      ("vol"), upon unprepared inspiratory efforts against a single-breath inspiratory
      threshold load ("single-breath"), and upon sustained inspiratory efforts against
      the same type of load ("continuous"). The slope of the relationship between
      diaphragm twitch transdiaphragmatic pressure and the underlying
      transdiaphragmatic pressure was -1.1 +/- 0.2 during "vol," -1.5 +/- 0.7 during
      "single-breath," and -0.6 +/- 0.4 during "continuous" (all slopes expressed in
      percent of baseline.percent of baseline-1) all comparisons significant at the 5%
      level. The contribution of the diaphragm to inspiration, as assessed by the
      gastric pressure to transdiaphragmatic pressure ratio, was 31 +/- 17% during
      "vol," 22 +/- 16% during "single-breath" (p = 0.13), and 19 +/- 9% during
      "continuous" (p = 0.0015 vs. "vol"). This study shows that the relationship
      between the amplitude of the transdiaphragmatic pressure produced by a diaphragm
      twitch and its counterpart produced by the underlying diaphragm contraction is
      not unequivocal. If twitch interpolation is interpreted as reflecting motoneuron
      recruitment, this study supports motor reorganization compatible with "diaphragm
      sparing" when an inspiratory threshold load becomes sustained.

PMID- 27891100
TI  - A Review about Functional Illiteracy: Definition, Cognitive, Linguistic, and
      Numerical Aspects.
AB  - Formally, availability of education for children has increased around the world
      over the last decades. However, despite having a successful formal education
      career, adults can become functional illiterates. Functional illiteracy means
      that a person cannot use reading, writing, and calculation skills for his/her own
      and the community's development. Functional illiteracy has considerable negative
      effects not only on personal development, but also in economic and social terms.
      Although functional illiteracy has been highly publicized in mass media in the
      recent years, there is limited scientific knowledge about the people termed
      functional illiterates; definition, assessment, and differential diagnoses with
      respect to related numerical and linguistic impairments are rarely studied and
      controversial. The first goal of our review is to give a comprehensive overview
      of the research on functional illiteracy by describing gaps in knowledge within
      the field and to outline and address the basic questions concerning who can be
      considered as functional illiterates: (1) Do they possess basic skills? (2) In
      which abilities do they have the largest deficits? (3) Are numerical and
      linguistic deficits related? (4) What is the fundamental reason for their
      difficulties? (5) Are there main differences between functional illiterates,
      illiterates, and dyslexics? We will see that despite partial evidence, there is
      still much research needed to answer these questions. Secondly, we emphasize the
      timeliness for a new and more precise definition that results in uniform
      sampling, better diagnosis, conclusion, and intervention. We propose the
      following working definition as the result of the review: functional illiteracy
      is the incapability to understand complex texts despite adequate schooling, age,
      language skills, elementary reading skills, and IQ. These inabilities must also
      not be fully explained by sensory, domain-general cognitive, neurological or
      mental disorders. In sum, we suggest that functional illiteracy must be more
      thoroughly understood and assessed from a theoretical, empirical, and diagnostic
      perspective.

PMID- 27891101
TI  - Spatio-Temporal Structure, Path Characteristics, and Perceptual Grouping in
      Immediate Serial Spatial Recall.
AB  - Immediate serial spatial recall measures the ability to retain sequences of
      locations in short-term memory and is considered the spatial equivalent of digit
      span. It is tested by requiring participants to reproduce sequences of movements
      performed by an experimenter or displayed on a monitor. Different organizational
      factors dramatically affect serial spatial recall but they are often confounded
      or underspecified. Untangling them is crucial for the characterization of working
      memory models and for establishing the contribution of structure and memory
      capacity to spatial span. We report five experiments assessing the relative role
      and independence of factors that have been reported in the literature. Experiment
      1 disentangled the effects of spatial clustering and path-length by manipulating
      the distance of items displayed on a touchscreen monitor. Long-path sequences
      segregated by spatial clusters were compared with short-path sequences not
      segregated by clusters. Recall was more accurate for sequences segregated by
      clusters independently from path-length. Experiment 2 featured conditions where
      temporal pauses were introduced between or within cluster boundaries during the
      presentation of sequences with the same paths. Thus, the temporal structure of
      the sequences was either consistent or inconsistent with a hierarchical
      representation based on segmentation by spatial clusters but the effect of
      structure could not be confounded with effects of path-characteristics. Pauses at
      cluster boundaries yielded more accurate recall, as predicted by a hierarchical
      model. In Experiment 3, the systematic manipulation of sequence structure, path
      length, and presence of path-crossings of sequences showed that structure
      explained most of the variance, followed by the presence/absence of path
      crossings, and path-length. Experiments 4 and 5 replicated the results of the
      previous experiments in immersive virtual reality navigation tasks where the
      viewpoint of the observer changed dynamically during encoding and recall. This
      suggested that the effects of structure in spatial span are not dependent on
      perceptual grouping processes induced by the aerial view of the stimulus array
      typically afforded by spatial recall tasks. These results demonstrate the
      independence of coding strategies based on structure from effects of path
      characteristics and perceptual grouping in immediate serial spatial recall.

PMID- 27891102
TI  - The Agreement between Parent-Reported and Directly Measured Child Language and
      Parenting Behaviors.
AB  - Parenting behaviors are commonly targeted in early interventions to improve
      children's language development. Accurate measurement of both parenting behaviors
      and children's language outcomes is thus crucial for sensitive assessment of
      intervention outcomes. To date, only a small number of studies have compared
      parent-reported and directly measured behaviors, and these have been hampered by
      small sample sizes and inaccurate statistical techniques, such as correlations.
      The Bland-Altman Method and Reduced Major Axis regression represent more reliable
      alternatives because they allow us to quantify fixed and proportional bias
      between measures. In this study, we draw on data from two Australian early
      childhood cohorts (N = 201 parents and slow-to-talk toddlers aged 24 months; and
      N = 218 parents and children aged 6-36 months experiencing social adversity) to
      (1) examine agreement and quantify bias between parent-reported and direct
      measures, and (2) to determine socio-demographic predictors of the differences
      between parent-reported and direct measures. Measures of child language and
      parenting behaviors were collected from parents and their children. Our findings
      support the utility of the Bland-Altman Method and Reduced Major Axis regression
      in comparing measurement methods. Results indicated stronger agreement between
      parent-reported and directly measured child language, and poorer agreement
      between measures of parenting behaviors. Child age was associated with difference
      scores for child language; however, the direction varied for each cohort. Parents
      who rated their child's temperament as more difficult tended to report lower
      language scores on the parent questionnaire, compared to the directly measured
      scores. Older parents tended to report lower parenting responsiveness on the
      parent questionnaire, compared to directly measured scores. Finally, speaking a
      language other than English was associated with less responsive parenting
      behaviors on the videotaped observation compared to the parent questionnaire.
      Variation in patterns of agreement across the distribution of scores highlighted
      the importance of assessing agreement comprehensively, providing strong evidence
      that simple correlations are grossly insufficient for method comparisons. We
      discuss implications for researchers and clinicians, including guidance for
      measurement selection, and the potential to reduce financial and time-related
      expenses and improve data quality. Further research is required to determine
      whether findings described here are reflected in more representative populations.

PMID- 27891103
TI  - Aww: The Emotion of Perceiving Cuteness.

PMID- 27891104
TI  - Hoarding Symptoms Are Not Exclusive to Hoarders.
AB  - Hoarding disorder (HD) was originally conceptualized as a subcategory of
      obsessive compulsive disorder (OCD), and numerous studies have in fact focused
      exclusively on investigating the comorbidity between OCD and HD. Hoarding
      behavior can nevertheless also be found in other clinical populations and in
      particular in patients with eating disorders (ED), anxiety disorders (AD), major
      depression (MD), and psychotic disorders (PD). The current study was carried out
      with the aim of investigating, using a validated instrument such as the Saving
      Inventory-Revised (SI-R), the presence of HD symptoms in patients diagnosed with
      ED, AD, MD, and PD. Hoarding symptomatology was also assessed in groups of self
      identified hoarders and healthy controls. The results revealed that 22.5% of the
      ED patients exceeded the cut-off for the diagnosis of HD, followed by 7.7% of the
      patients with MD, 7.4% of the patients with AD, and 5.9% of the patients with PD.
      The patients with ED had significantly higher SI-R scores than the other groups
      in the Acquisition and Difficulty Discarding scales while the AD, MD, and PD
      patients were characterized exclusively by Difficulty Discarding. These data
      suggest to clinicians that hoarding symptoms should be assessed in other types of
      patients and especially in those affected by Bulimia and Binge eating.

PMID- 27891105
TI  - Global Cue Inconsistency Diminishes Learning of Cue Validity.
AB  - In daily life, we make decisions that are associated with probabilistic outcomes
      (e.g., the chance of rain today). People search for and utilize information that
      validly predicts an outcome (i.e., we look for dark clouds to indicate the
      possibility of rain). In the current study (N = 107), we present a two-stage
      learning task that examines how participants learn and utilize predictive
      information within a probabilistic learning environment. In the first stage,
      participants select one of three cues that gives predictive information about the
      outcome of the second stage. Participants then use this information to predict
      the outcome in stage two, for which they receive feedback. Critically, only one
      of the three cues in stage one gives valid predictive information about the
      outcome in stage two. Participants must differentiate the valid from non-valid
      cues and select this cue on subsequent trials in order to inform their prediction
      of the outcome in stage two. The validity of this predictive information,
      however, is reinforced with varying levels of probabilistic feedback (i.e., 75,
      85, 95, 100%). A second manipulation involved changing the consistency of the
      predictive information in stage one and the outcome in stage two. The results
      show that participants, with higher levels of probabilistic feedback, learned to
      utilize the valid cue. In inconsistent task conditions, however, participants
      were significantly less successful in utilizing higher validity cues. We
      interpret this result as implying that learning in probabilistic categorization
      is based on developing a representation of the task that allows for goal-directed
      action.

PMID- 27891106
TI  - Episodic and Semantic Memory Contribute to Familiar and Novel Episodic Future
      Thinking.
AB  - Increasing evidence indicates that episodic future thinking (EFT) relies on both
      episodic and semantic memory; however, event familiarity may importantly affect
      the extent to which episodic and semantic memory contribute to EFT. To test this
      possibility, two behavioral experiments were conducted. In Experiment 1, we
      directly compared the proportion of episodic and semantic memory used in an EFT
      task. The results indicated that more episodic memory was used when imagining
      familiar future events compared with novel future events. Conversely,
      significantly more semantic memory was used when imagining novel events compared
      with familiar events. Experiment 2 aimed to verify the results of Experiment 1.
      In Experiment 2, we found that familiarity moderated the effect of priming the
      episodic memory system on EFT; particularly, it increased the time required to
      construct a standard familiar episodic future event, but did not significantly
      affect novel episodic event reaction time. Collectively, these findings support
      the hypothesis that event familiarity importantly moderates episodic and semantic
      memory's contribution to EFT.

PMID- 27891107
TI  - Internet-Communication Disorder: It's a Matter of Social Aspects, Coping, and
      Internet-Use Expectancies.
AB  - Online communication applications such as Facebook, WhatsApp, and Twitter are
      some of the most frequently used Internet applications. There is a growing amount
      of individuals suffering diminished control over their use of online
      communication applications which leads to diverse negative consequences in
      offline life. This could be referred to as Internet-communication disorder (ICD).
      The current study investigates the role of individual characteristics (e.g.,
      psychopathological symptoms, feelings of loneliness) and specific cognitions. In
      a sample of 485 participants a structural equation model was tested to
      investigate predictors and mediators which may predict an excessive use. The
      results emphasize that a higher level of social loneliness and less perceived
      social support enhance the risk of a pathological use. The effects of
      psychopathological symptoms (depression and social anxiety) as well as individual
      characteristics (self-esteem, self-efficacy, and stress vulnerability) on ICD
      symptoms are mediated by Internet-use expectancies and dysfunctional coping
      mechanisms. The results illustrate mediation effects which are in line with the
      theoretical model by Brand et al. (2016). As suggested in the model social
      aspects seem to be key predictors of ICD symptoms. Further research should
      investigate convergent and divergent factors of other types of specific Internet
      use disorders.

PMID- 27891108
TI  - The Mediating Role of Psychological Adjustment between Peer Victimization and
      Social Adjustment in Adolescence.
AB  - There is extensive scientific evidence of the serious psychological and social
      effects that peer victimization may have on students, among them internalizing
      problems such as anxiety or negative self-esteem, difficulties related to low
      self-efficacy and lower levels of social adjustment. Although a direct
      relationship has been observed between victimization and these effects, it has
      not yet been analyzed whether there is a relationship of interdependence between
      all these measures of psychosocial adjustment. The aim of this study was to
      examine the relationship between victimization and difficulties related to social
      adjustment among high school students. To do so, various explanatory models were
      tested to determine whether psychological adjustment (negative self-esteem,
      social anxiety and social self-efficacy) could play a mediating role in this
      relationship, as suggested by other studies on academic adjustment. The sample
      comprised 2060 Spanish high school students (47.9% girls; mean age = 14.34). The
      instruments used were the scale of victimization from European Bullying
      Intervention Project Questionnaire, the negative scale from Rosenberg Self-Esteem
      Scale, Social Anxiety Scale for Adolescents and a general item about social self
      efficacy, all of them self-reports. Structural equation modeling was used to
      analyze the data. The results confirmed the partial mediating role of negative
      self-esteem, social anxiety and social self-efficacy between peer victimization
      and social adjustment and highlight the importance of empowering victimized
      students to improve their self-esteem and self-efficacy and prevent social
      anxiety. Such problems lead to the avoidance of social interactions and social
      reinforcement, thus making it difficult for these students to achieve adequate
      social adjustment.

PMID- 27891109
TI  - Pulling Rank: Military Rank Affects Hormone Levels and Fairness in an Allocation
      Experiment.
AB  - Status within social hierarchies has great effects on the lives of socially
      organized mammals. Its effects on human behavior and related physiology, however,
      is relatively little studied. The present study investigated the impact of
      military rank on fairness and behavior in relation to salivary cortisol (C) and
      testosterone (T) levels in male soldiers. For this purpose 180 members of the
      Austrian Armed Forces belonging to two distinct rank groups participated in two
      variations of a computer-based guard duty allocation experiment. The rank groups
      were (1) warrant officers (high rank, HR) and (2) enlisted men (low rank, LR).
      One soldier from each rank group participated in every experiment. At the
      beginning of the experiment, one participant was assigned to start standing guard
      and the other participant at rest. The participant who started at rest could
      choose if and when to relieve his fellow soldier and therefore had control over
      the experiment. In order to trigger perception of unfair behavior, an additional
      experiment was conducted which was manipulated by the experimenter. In the
      manipulated version both soldiers started in the standing guard position and were
      never relieved, believing that their opponent was at rest, not relieving them.
      Our aim was to test whether unfair behavior causes a physiological reaction.
      Saliva samples for hormone analysis were collected at regular intervals
      throughout the experiment. We found that in the un-manipulated setup high-ranking
      soldiers spent less time standing guard than lower ranking individuals. Rank was
      a significant predictor for C but not for T levels during the experiment. C
      levels in the HR group were higher than in the LR group. C levels were also
      elevated in the manipulated experiment compared to the un-manipulated experiment,
      especially in LR. We assume that the elevated C levels in HR were caused by HR
      feeling their status challenged by the situation of having to negotiate with an
      individual of lower military rank. This would be in line with the observation
      that unequally shared duty favored HR in most cases. We conclude that social
      status, in the form of military rank affects fairness behavior in social
      interaction and endocrine levels.

PMID- 27891110
TI  - "My Child has Cerebral Palsy": Parental Involvement and Children's School
      Engagement.
AB  - Engaged students tend to show school-committed behaviors (e.g., attend classes,
      get involved with the learning process), high achievement, and sense of
      belonging. However, students with disabilities are prone to show a lack of
      engagement with school due to the specific difficulties they have to handle. In
      fact, children with disabilities are likely to show poor participation in school
      when compared with children without disabilities. This poor involvement is
      related to their low autonomy to participate in the school activities, which, in
      turn, results in low school engagement. Parents play a crucial role in their
      children's education. Parental involvement in school activities promotes
      autonomous behaviors and, consequently, school engagement. In fact, extant
      literature has shown close relationships between parental involvement, school
      engagement, and academic performance. Yet, parental involvement in school
      activities of children with Cerebral Palsy (CP) has received little direct
      attention from researchers. These children tend to display lower participation
      due to the motor, or cognitive, impairments that compromise their autonomy, and
      have a high likelihood to develop learning disabilities, with special incidences
      in reading and arithmetic. Therefore, our aim is twofold, to understand the
      parental styles; and how the perceived parental involvement in school activities
      is related to their children school engagement. Hence, 19 interviews were
      conducted with one of the parents of 19 children with CP. These interviews
      explored the school routines of children and the perceived involvement of parents
      in those routines. Additionally, children filled out a questionnaire on school
      engagement. Results show that the majority of the parents were clustered in the
      Autonomy Allowance and Acceptance and Support parental style, and the majority of
      their children were perceived as autonomous. Moreover, about a half of the
      children reported a high level of school engagement. Finally, neither children's
      autonomous behaviors reported by parents, nor parental style, seem to be related
      with the children's level of school engagement. Rehabilitation centers and
      schools could consider training parents/caregivers focusing on their educational
      needs, promotion of reflections on the usefulness of applying autonomy promotion
      strategies with their child, and foster their involvement.

PMID- 27891111
TI  - Editorial: Brain Oscillations and Predictive Coding in the Context of Different
      Conscious States and Sleep-Wake Cycle: Implications for Decision Making and
      Psychopathology.

PMID- 27891113
TI  - The Impact of Silver Nanoparticles Produced by Bacillus pumilus As Antimicrobial
      and Nematicide.
AB  - This study evaluates the potential application of silver nanoparticles (AgNPs) as
      antimicrobial or nematicidal agents produced by the extremophile Bacillus
      pumilus, which was isolated from the alkaline Wadi El-Natrun Lake in Egypt. The
      AgNPs were characterized by ultraviolet-visible absorption spectroscopy,
      transmission electron microscopy, and energy dispersive x-ray spectroscopy. The
      size of AgNPs formed ranged from 20.12 to 29.48 nm. Panagrellus redivivus was
      exposed to different concentrations (0, 50, 100, 150, and 200 MUg/mL) of AgNPs in
      a 5 mL nematode suspension (1 * 103 mL-1). The best result occurred at AgNP
      concentrations of 150 and 200 MUg/mL, with death rates of 80 and 91%,
      respectively, following 48 h of exposure. AgNPs also exhibited potent
      antimicrobial properties when using Gram-negative and Gram-positive human
      pathogens, with MIC and MBC values of 5 and 10 MUg/mL, respectively. These
      laboratory assays prove that biologically synthesized AgNPs are an ecofriendly
      material that can be used in lieu of solvents or toxic chemicals.

PMID- 27891112
TI  - Deep Brain Stimulation for Tourette's Syndrome: The Case for Targeting the
      Thalamic Centromedian-Parafascicular Complex.
AB  - Tourette's syndrome (TS) is a neurologic condition characterized by both motor
      and phonic tics and is typically associated with psychiatric comorbidities,
      including obsessive-compulsive disorder/behavior and attention-deficit
      hyperactivity disorder, and can be psychologically and socially debilitating. It
      is considered a disorder of the cortico-striato-thalamo-cortical circuitry, as
      suggested by pathophysiology studies and therapeutic options. Among these, deep
      brain stimulation (DBS) of the centromedian-parafascicular nucleus (CM-Pf) of the
      thalamus is emerging as a valuable treatment modality for patients affected by
      severe, treatment-resistant TS. Here, we review the most recent experimental
      evidence for the pivotal role of CM-Pf in the pathophysiology of TS, discuss
      potential mechanisms of action that may mediate the effects of CM-Pf DBS in TS,
      and summarize its clinical efficacy.

PMID- 27891114
TI  - Comparative Analysis of Two Helicobacter pylori Strains using Genomics and Mass
      Spectrometry-Based Proteomics.
AB  - Helicobacter pylori, a gastroenteric pathogen believed to have co-evolved with
      humans over 100,000 years, shows significant genetic variability. This motivates
      the study of different H. pylori strains and the diseases they cause in order to
      identify determinants for disease evolution. In this study, we used proteomics
      tools to compare two H. pylori strains. Nic25_A was isolated in Nicaragua from a
      patient with intestinal metaplasia, and P12 was isolated in Europe from a patient
      with duodenal ulcers. Differences in the abundance of surface proteins between
      the two strains were determined with two mass spectrometry-based methods, label
      free quantification (MaxQuant) or the use of tandem mass tags (TMT). Each
      approach used a lipid-based protein immobilization (LPITM) technique to enrich
      peptides of surface proteins. Using the MaxQuant software, we found 52 proteins
      that differed significantly in abundance between the two strains (up- or
      downregulated by a factor of 1.5); with TMT, we found 18 proteins that differed
      in abundance between the strains. Strain P12 had a higher abundance of proteins
      encoded by the cag pathogenicity island, while levels of the acid response
      regulator ArsR and its regulatory targets (KatA, AmiE, and proteins involved in
      urease production) were higher in strain Nic25_A. Our results show that
      differences in protein abundance between H. pylori strains can be detected with
      proteomic approaches; this could have important implications for the study of
      disease progression.

PMID- 27891115
TI  - Methanotrophy under Versatile Conditions in the Water Column of the Ferruginous
      Meromictic Lake La Cruz (Spain).
AB  - Lakes represent a considerable natural source of methane to the atmosphere
      compared to their small global surface area. Methanotrophs in sediments and in
      the water column largely control methane fluxes from these systems, yet the
      diversity, electron accepting capacity, and nutrient requirements of these
      microorganisms have only been partially identified. Here, we investigated the
      role of electron acceptors alternative to oxygen and sulfate in microbial methane
      oxidation at the oxycline and in anoxic waters of the ferruginous meromictic Lake
      La Cruz, Spain. Active methane turnover in a zone extending well below the
      oxycline was evidenced by stable carbon isotope-based rate measurements. We
      observed a strong methane oxidation potential throughout the anoxic water column,
      which did not vary substantially from that at the oxic/anoxic interface. Both in
      the redox-transition and anoxic zones, only aerobic methane-oxidizing bacteria
      (MOB) were detected by fluorescence in situ hybridization and sequencing
      techniques, suggesting a close coupling of cryptic photosynthetic oxygen
      production and aerobic methane turnover. Additions of nitrate, nitrite and to a
      lesser degree iron and manganese oxides also stimulated bacterial methane
      consumption. We could not confirm a direct link between the reduction of these
      compounds and methane oxidation and we cannot exclude the contribution of unknown
      anaerobic methanotrophs. Nevertheless, our findings from Lake La Cruz support
      recent laboratory evidence that aerobic methanotrophs may be able to utilize
      alternative terminal electron acceptors under oxygen limitation.

PMID- 27891116
TI  - Complete Genome Sequence of Clostridium estertheticum DSM 8809, a Microbe
      Identified in Spoiled Vacuum Packed Beef.
AB  - Blown pack spoilage (BPS) is a major issue for the beef industry. Etiological
      agents of BPS involve members of a group of Clostridium species, including
      Clostridium estertheticum which has the ability to produce gas, mostly carbon
      dioxide, under anaerobic psychotrophic growth conditions. This spore-forming
      bacterium grows slowly under laboratory conditions, and it can take up to 3
      months to produce a workable culture. These characteristics have limited the
      study of this commercially challenging bacterium. Consequently information on
      this bacterium is limited and no effective controls are currently available to
      confidently detect and manage this production risk. In this study the complete
      genome of C. estertheticum DSM 8809 was determined by SMRT(r) sequencing. The
      genome consists of a circular chromosome of 4.7 Mbp along with a single plasmid
      carrying a potential tellurite resistance gene tehB and a Tn3-like resolvase
      encoding gene tnpR. The genome sequence was searched for central metabolic
      pathways that would support its biochemical profile and several enzymes
      contributing to this phenotype were identified. Several putative
      antibiotic/biocide/metal resistance-encoding genes and virulence factors were
      also identified in the genome, a feature that requires further research. The
      availability of the genome sequence will provide a basic blueprint from which to
      develop valuable biomarkers that could support and improve the detection and
      control of this bacterium along the beef production chain.

PMID- 27891117
TI  - Disruption of the Gene Encoding Endo-beta-1, 4-Xylanase Affects the Growth and
      Virulence of Sclerotinia sclerotiorum.
AB  - Sclerotinia sclerotiorum (Lib.) de Bary is a devastating fungal pathogen with
      worldwide distribution. S. sclerotiorum is a necrotrophic fungus that secretes
      many cell wall-degrading enzymes (CWDEs) that destroy plant's cell-wall
      components. Functional analyses of the genes that encode CWDEs will help explain
      the mechanisms of growth and pathogenicity of S. sclerotiorum. Here, we isolated
      and characterized a gene SsXyl1 that encoded an endo-beta-1, 4-xylanase in S.
      sclerotiorum. The SsXyl1 expression showed a slight increase during the
      development and germination stages of sclerotia and a dramatic increase during
      infection. The expression of SsXyl1 was induced by xylan. The SsXyl1 deletion
      strains produce aberrant sclerotia that could not germinate to form apothecia.
      The SsXyl1 deletion strains also lost virulence to the hosts. This study
      demonstrates the important roles of endo-beta-1, 4-xylanase in the growth and
      virulence of S. sclerotiorum.

PMID- 27891119
TI  - Variability in DPA and Calcium Content in the Spores of Clostridium Species.
AB  - Spores of a number of clostridial species, and their resistance to thermal
      treatment is a major concern for the food industry. Spore resistance to wet heat
      is related to the level of spore hydration, which is inversely correlated with
      the content of calcium and dipicolinic acid (DPA) in the spore core. It is widely
      believed that the accumulation of DPA and calcium in the spore core is a
      fundamental component of the sporulation process for all endospore forming
      species. We have noticed heterogeneity in the heat resistance capacity and
      overall DPA/calcium content among the spores of several species belonging to
      Clostridium sensu stricto group: two C. acetobutylicum strains (DSM 792 and
      1731), two C. beijerinckii strains (DSM 791 and NCIMB 8052), and a C.
      collagenovorans strain (DSM 3089). A C. beijerinckii strain (DSM 791) and a C.
      acetobutylicum strain (DSM 792) display low Ca and DPA levels. In addition, these
      two species, with the lowest average Ca/DPA content amongst the strains
      considered, also exhibit minimal heat resistance. There appears to be no
      correlation between the Ca/DPA content and the phylogenetic distribution of the
      C. acetobutylicum and C. beijerinckii species based either on the 16S rRNA or the
      spoVA gene. This finding suggests that a subset of Clostridium sensu stricto
      species produce spores with low resistance to wet heat. Additionally, analysis of
      individual spores using STEM-EDS and STXM revealed that DPA and calcium levels
      can also vary amongst individual spores in a single spore population.

PMID- 27891120
TI  - Two Major Clades of Bradyrhizobia Dominate Symbiotic Interactions with Pigeonpea
      in Fields of Cote d'Ivoire.
AB  - In smallholder farms of Cote d'Ivoire, particularly in the northeast of the
      country, Cajanus cajan (pigeonpea) has become an important crop because of its
      multiple beneficial facets. Pigeonpea seeds provide food to make ends meet, are
      sold on local markets, and aerial parts serve as forage for animals. Since it
      fixes atmospheric nitrogen in symbiosis with soil bacteria collectively known as
      rhizobia, C. cajan also improves soil fertility and reduces fallow time. Yet,
      seed yields remain low mostly because farmers cannot afford chemical fertilizers.
      To identify local rhizobial strains susceptible to be used as bio-inoculants to
      foster pigeonpea growth, root nodules were collected in six fields of three
      geographically distant regions of Cote d'Ivoire. Nodule bacteria were isolated
      and characterized using various molecular techniques including matrix-assisted
      laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS) and
      DNA sequencing. These molecular analyses showed that 63 out of 85 nodule isolates
      belonged to two major clades of bradyrhizobia, one of which is known as the
      Bradyrhizobium elkanii super clade. Phylogenies of housekeeping (16S-ITS-23S,
      rpoB) and symbiotic (nifH) genes were not always congruent suggesting that
      lateral transfer of nitrogen fixation genes also contributed to define the genome
      of these bradyrhizobial isolates. Interestingly, no field-, plant-, or cultivar
      specific effect was found to shape the profiles of symbiotic strains. In
      addition, nodule isolates CI-1B, CI-36E, and CI-41A that belong to distinct
      species, showed similar symbiotic efficiencies suggesting that any of these
      strains might serve as a proficient inoculant for C. cajan.

PMID- 27891118
TI  - Colistin in Pig Production: Chemistry, Mechanism of Antibacterial Action,
      Microbial Resistance Emergence, and One Health Perspectives.
AB  - Colistin (Polymyxin E) is one of the few cationic antimicrobial peptides
      commercialized in both human and veterinary medicine. For several years now,
      colistin has been considered the last line of defense against infections caused
      by multidrug-resistant Gram-negative such as Acinetobacter baumannii, Pseudomonas
      aeruginosa, and Klebsiella pneumoniae. Colistin has been extensively used orally
      since the 1960s in food animals and particularly in swine for the control of
      Enterobacteriaceae infections. However, with the recent discovery of plasmid
      mediated colistin resistance encoded by the mcr-1 gene and the higher prevalence
      of samples harboring this gene in animal isolates compared to other origins,
      livestock has been singled out as the principal reservoir for colistin resistance
      amplification and spread. Co-localization of the mcr-1 gene and Extended-Spectrum
      beta-Lactamase genes on a unique plasmid has been also identified in many
      isolates from animal origin. The use of colistin in pigs as a growth promoter and
      for prophylaxis purposes should be banned, and the implantation of sustainable
      measures in pig farms for microbial infection prevention should be actively
      encouraged and financed. The scientific research should be encouraged in swine
      medicine to generate data helping to reduce the exacerbation of colistin
      resistance in pigs and in manure. The establishment of guidelines ensuring a
      judicious therapeutic use of colistin in pigs, in countries where this drug is
      approved, is of crucial importance. The implementation of a microbiological
      withdrawal period that could reduce the potential contamination of consumers with
      colistin resistant bacteria of porcine origin should be encouraged. Moreover, the
      management of colistin resistance at the human-pig-environment interface requires
      the urgent use of the One Health approach for effective control and prevention.
      This approach needs the collaborative effort of multiple disciplines and close
      cooperation between physicians, veterinarians, and other scientific health and
      environmental professionals. This review is an update on the chemistry of
      colistin, its applications and antibacterial mechanism of action, and on
      Enterobacteriaceae resistance to colistin in pigs. We also detail and discuss the
      One Health approach and propose guidelines for colistin resistance management.

PMID- 27891121
TI  - Hypovirulence of Sclerotium rolfsii Caused by Associated RNA Mycovirus.
AB  - Mycoviruses associated with hypovirulence are potential biological control agents
      and could be useful to study the pathogenesis of fungal host pathogens.
      Sclerotium rolfsii, a pathogenic fungus, causes southern blight in a wide variety
      of crops. In this study, we isolated a series of dsRNAs from a debilitated S.
      rolfsii strain, BLH-1, which had pronounced phenotypic aberrations including
      reduced pathogenicity, mycelial growth and deficient sclerotia production. Virus
      curing and horizontal transmission experiments that eliminated or transmitted,
      respectively, all dsRNA elements showed that the dsRNAs were involved in the
      hypovirulent traits of BLH-1. Ultrastructure examination also showed hyphae
      fracture and cytoplasm or organelle degeneration in BLH-1 hyphal cells compared
      to the virus-free strain. Three assembled cDNA contigs generated from the cDNA
      library cloned from the purified dsRNA indicated that strain BLH-1 was infected
      by at least three novel mycoviruses. One has similarity to the hypovirulence
      associated Sclerotinia sclerotiorum hypovirus 2 (SsHV2) in the family
      Hypoviridae, and the other two are related to two different unclassified dsRNA
      mycovirus families. To our knowledge, this is the first report of S. rolfsii
      hypovirulence that was correlated with its associated dsRNA.

PMID- 27891123
TI  - Editorial: The Role of Microbial Communities in Tropical Ecosystems.

PMID- 27891122
TI  - Membrane-Active Epithelial Keratin 6A Fragments (KAMPs) Are Unique Human
      Antimicrobial Peptides with a Non-alphabeta Structure.
AB  - Antibiotic resistance is a pressing global health problem that threatens millions
      of lives each year. Natural antimicrobial peptides and their synthetic
      derivatives, including peptoids and peptidomimetics, are promising candidates as
      novel antibiotics. Recently, the C-terminal glycine-rich fragments of human
      epithelial keratin 6A were found to have bactericidal and cytoprotective
      activities. Here, we used an improved 2-dimensional NMR method coupled with a new
      protocol for structural refinement by low temperature simulated annealing to
      characterize the solution structure of these kerain-derived antimicrobial
      peptides (KAMPs). Two specific KAMPs in complex with membrane mimicking sodium
      dodecyl sulfate (SDS) micelles displayed amphipathic conformations with only
      local bends and turns, and a central 10-residue glycine-rich hydrophobic strip
      that is central to bactericidal activity. To our knowledge, this is the first
      report of non-alphabeta structure for human antimicrobial peptides. Direct
      observation of Staphylococcus aureus and Pseudomonas aeruginosa by scanning and
      transmission electron microscopy showed that KAMPs deformed bacterial cell
      envelopes and induced pore formation. Notably, in competitive binding
      experiments, KAMPs demonstrated binding affinities to LPS and LTA that did not
      correlate with their bactericidal activities, suggesting peptide-LPS and peptide
      LTA interactions are less important in their mechanisms of action. Moreover,
      immunoprecipitation of KAMPs-bacterial factor complexes indicated that membrane
      surface lipoprotein SlyB and intracellular machineries NQR sodium pump and
      ribosomes are potential molecular targets for the peptides. Results of this study
      improve our understanding of the bactericidal function of epithelial cytokeratin
      fragments, and highlight an unexplored class of human antimicrobial peptides,
      which may serve as non-alphabeta peptide scaffolds for the design of novel
      peptide-based antibiotics.

PMID- 27891124
TI  - A Novel Cell Type Enables B. subtilis to Escape from Unsuccessful Sporulation in
      Minimal Medium.
AB  - Sporulation is the most enduring survival strategy developed by several bacterial
      species. However, spore development of the model organism Bacillus subtilis has
      mainly been studied by means of media or conditions optimized for the induction
      of sporogenesis. Here, I show that during prolonged growth during stationary
      phase in minimal medium, B. subtilis undergoes an asymmetric cell division that
      produces small and round-shaped, DNA containing cells. In contrast to wild-type
      cells, mutants harboring spo0A or spoIIIE/sftA double mutations neither sporulate
      nor produce this special cell type, providing evidence that the small round cells
      emerge from the abortion of endospore formation. In most cases observed, the
      small round cells arise in the presence of sigma H but absence of sigma F
      activity, different from cases of abortive sporulation described for rich media.
      These data suggest that in minimal media, many cells are able to initiate but
      fail to complete spore development, and therefore return to normal growth as
      rods. This work reveals that the continuation of asymmetric cell division, which
      results in the formation of the small round cells, is a way for cells to delay or
      escape from-unsuccessful-sporulation. Based on these findings, I suggest to name
      the here described cell type as "dwarf cells" to distinguish them from the well
      known minicells observed in mutants defective in septum placement or proper
      chromosome partitioning.

PMID- 27891125
TI  - Poly-gamma-Glutamic Acids Contribute to Biofilm Formation and Plant Root
      Colonization in Selected Environmental Isolates of Bacillus subtilis.
AB  - Bacillus subtilis is long known to produce poly-gamma-glutamic acids (gamma-PGA)
      as one of the major secreted polymeric substances. In B. subtilis, the regulation
      of gamma-PGA production and its physiological role are still unclear. B. subtilis
      is also capable of forming structurally complex multicellular communities, or
      biofilms, in which an extracellular matrix consisting of secreted proteins and
      polysaccharides holds individual cells together. Biofilms were shown to
      facilitate B. subtilis-plant interactions. In this study, we show that different
      environmental isolates of B. subtilis, all capable of forming biofilms, vary
      significantly in gamma-PGA production. This is possibly due to differential
      regulation of gamma-PGA biosynthesis genes. In many of those environmental
      isolates, gamma-PGA seems to contribute to robustness and complex morphology of
      the colony biofilms, suggesting a role of gamma-PGA in biofilm formation. Our
      evidence further shows that in selected B. subtilis strains, gamma-PGA also plays
      a role in root colonization by the bacteria, pinpointing a possible function of
      gamma-PGA in B. subtilis-plant interactions. Finally, we found that several
      pathways co-regulate both gamma-PGA biosynthesis genes and genes for the biofilm
      matrix in B. subtilis, but in an opposing fashion. We discussed potential
      biological significance of that.

PMID- 27891126
TI  - The Ly49E Receptor Inhibits the Immune Control of Acute Trypanosoma cruzi
      Infection.
AB  - The protozoan parasite Trypanosoma cruzi circulates in the blood upon infection
      and invades various cells. Parasites intensively multiply during the acute phase
      of infection and persist lifelong at low levels in tissues and blood during the
      chronic phase. Natural killer (NK) and NKT cells play an important role in the
      immune control of T. cruzi infection, mainly by releasing the cytokine IFN-gamma
      that activates the microbicidal action of macrophages and other cells and shapes
      a protective type 1 immune response. The mechanisms by which immune cells are
      regulated to produce IFN-gamma during T. cruzi infection are still incompletely
      understood. Here, we show that urokinase plasminogen activator (uPA) is induced
      early upon T. cruzi infection and remains elevated until day 20 post-infection.
      We previously demonstrated that the inhibitory receptor Ly49E, which is
      expressed, among others, on NK and NKT cells, is triggered by uPA. Therefore, we
      compared wild type (WT) to Ly49E knockout (KO) mice for their control of
      experimental T. cruzi infection. Our results show that young, i.e., 4- and 6-week
      old, Ly49E KO mice control the infection better than WT mice, indicated by a
      lower parasite load and less cachexia. The beneficial effect of Ly49E depletion
      is more obvious in 4-week-old male than in female mice and weakens in 8-week-old
      mice. In young mice, the lower T. cruzi parasitemia in Ly49E KO mice is
      paralleled by higher IFN-gamma production compared to their WT controls. Our data
      indicate that Ly49E receptor expression inhibits the immune control of T. cruzi
      infection. This is the first demonstration that the inhibitory Ly49E receptor can
      interfere with the immune response to a pathogen in vivo.

PMID- 27891129
TI  - Immunological and Translational Aspects of NK Cell-Based Antitumor
      Immunotherapies.
AB  - Natural killer (NK) cells play a pivotal role in the first line of defense
      against cancer. NK cells that are deficient in CD3 and a clonal T cell receptor
      (TCR) can be subdivided into two major subtypes, CD56dimCD16+ cytotoxic and
      CD56brightCD16- immunoregulatory NK cells. Cytotoxic NK cells not only directly
      kill tumor cells without previous stimulation by cytotoxic effector molecules,
      such as perforin and granzymes or via death receptor interactions, but also act
      as regulatory cells for the immune system by secreting cytokines and chemokines.
      The aim of this review is to highlight therapeutic strategies utilizing
      autologous and allogenic NK cells, combinations of NK cells with monoclonal
      antibodies to induce antibody-dependent cellular cytotoxicity, or immune
      checkpoint inhibitors. Additionally, we discuss the use of chimeric antigen
      receptor-engineered NK cells in cancer immunotherapy.

PMID- 27891128
TI  - Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers
      and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets.
AB  - Non-alcoholic fatty liver disease (NAFLD) is an increasing problem worldwide and
      is associated with negative outcomes such as cirrhosis, hepatocellular carcinoma,
      insulin resistance, diabetes, and cardiovascular events. Current evidence shows
      that the immune response has an important participation driving the initiation,
      maintenance, and progression of the disease. So, various immune imbalances, from
      cellular to cytokines levels, have been studied, either for better compression of
      the disease pathophysiology or as biomarkers for severity assessment and outcome
      prediction. In this article, we performed a thorough review of studies that
      evaluated the role of inflammatory/immune imbalances in the NAFLD. At the
      cellular level, we gave special focus on the imbalance between neutrophils and
      lymphocytes counts (the neutrophil-to-lymphocyte ratio), and that which occurs
      between T helper 17 (Th17) and regulatory T cells as emerging biomarkers. By
      extension, we reviewed the reflection of these imbalances at the molecular level
      through pro-inflammatory cytokines including those involved in Th17
      differentiation (IL-6, IL-21, IL-23, and transforming growth factor-beta), and
      those released by Th17 cells (IL-17A, IL-17F, IL-21, and IL-22). We gave
      particular attention to the role of IL-17, either produced by Th17 cells or
      neutrophils, in fibrogenesis and steatohepatitis. Finally, we reviewed the
      potential of these pathways as new therapeutic targets in NAFLD.

PMID- 27891130
TI  - Molecular Mechanisms That Underlie the Dynamic Adaptation of Innate Monocyte
      Memory to Varying Stimulant Strength of TLR Ligands.
AB  - In adaptation to rising stimulant strength, innate monocytes can be dynamically
      programed to preferentially express either pro- or anti-inflammatory mediators.
      Such dynamic innate adaptation or programing may bear profound relevance in host
      health and disease. However, molecular mechanisms that govern innate adaptation
      to varying strength of stimulants are not well understood. Using
      lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we
      reported that the expressions of pro-inflammatory mediators are preferentially
      sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in
      monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by
      super-low dose LPS exhibited higher levels of transcription factor, interferon
      regulatory factor 5 (IRF5), and reduced levels of transcriptional modulator B
      lymphocyte-induced maturation protein-1 (Blimp-1). Intriguingly, the inflammatory
      monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not
      MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and
      tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp
      contrast, rising doses of TLR3 agonist preferentially caused inflammatory
      adaptation without inducing tolerance. At the molecular level, the differential
      regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics
      by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the
      understanding of monocyte adaptation and memory toward distinct TLR ligands.

PMID- 27891131
TI  - Viral Evasion Strategies in Type I IFN Signaling - A Summary of Recent
      Developments.
AB  - The immune system protects the organism against infections and the damage
      associated with them. The first line of defense against pathogens is the innate
      immune response. In the case of a viral infection, it induces the interferon
      (IFN) signaling cascade and eventually the expression of type I IFN, which then
      causes an antiviral state in the cells. However, many viruses have developed
      strategies to counteract this mechanism and prevent the production of IFN. In
      order to modulate or inhibit the IFN signaling cascade in their favor, viruses
      have found ways to interfere at every single step of the cascade, for example, by
      inducing protein degradation or cleavage, or by mediate protein
      polyubiquitination. In this article, we will review examples of viruses that
      modulate the IFN response and describe the mechanisms they use.

PMID- 27891133
TI  - Modeling Long-Term Corn Yield Response to Nitrogen Rate and Crop Rotation.
AB  - Improved prediction of optimal N fertilizer rates for corn (Zea mays L.) can
      reduce N losses and increase profits. We tested the ability of the Agricultural
      Production Systems sIMulator (APSIM) to simulate corn and soybean (Glycine max
      L.) yields, the economic optimum N rate (EONR) using a 16-year field-experiment
      dataset from central Iowa, USA that included two crop sequences (continuous corn
      and soybean-corn) and five N fertilizer rates (0, 67, 134, 201, and 268 kg N ha
      1) applied to corn. Our objectives were to: (a) quantify model prediction
      accuracy before and after calibration, and report calibration steps; (b) compare
      crop model-based techniques in estimating optimal N rate for corn; and (c)
      utilize the calibrated model to explain factors causing year to year variability
      in yield and optimal N. Results indicated that the model simulated well long-term
      crop yields response to N (relative root mean square error, RRMSE of 19.6% before
      and 12.3% after calibration), which provided strong evidence that important soil
      and crop processes were accounted for in the model. The prediction of EONR was
      more complex and had greater uncertainty than the prediction of crop yield (RRMSE
      of 44.5% before and 36.6% after calibration). For long-term site mean EONR
      predictions, both calibrated and uncalibrated versions can be used as the 16-year
      mean differences in EONR's were within the historical N rate error range (40-50
      kg N ha-1). However, for accurate year-by-year simulation of EONR the calibrated
      version should be used. Model analysis revealed that higher EONR values in years
      with above normal spring precipitation were caused by an exponential increase in
      N loss (denitrification and leaching) with precipitation. We concluded that long
      term experimental data were valuable in testing and refining APSIM predictions.
      The model can be used as a tool to assist N management guidelines in the US
      Midwest and we identified five avenues on how the model can add value toward
      agronomic, economic, and environmental sustainability.

PMID- 27891132
TI  - Impact of Chronic HIV/SIV Infection on T Follicular Helper Cell Subsets and
      Germinal Center Homeostasis.
AB  - The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has
      renewed optimism for developing an effective vaccine against HIV-1. The
      generation of most bNAbs requires multiple rounds of B cell receptor affinity
      maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their
      production. However, less than 1% of HIV-infected patients develop bNAbs that
      arise late in the course of infection, indicating probable Tfh and B cell
      dysfunctions in this context. Since the last few years, many studies have
      characterized Tfh cells from lymph nodes and spleen of HIV-infected individuals
      and SIV-infected macaques. Various lymphoid Tfh cell subsets have been
      identified, including precursor Tfh (pTfh), germinal center Tfh (GC Tfh), and the
      regulatory counterpart of Tfh cells, the follicular regulatory T cells. The
      latter have been reported to play a crucial role in the control of T and B cell
      crosstalk and GC reactions. More recently, circulating Tfh-like cells (cTfh) have
      been identified. Meanwhile, advances in single-cell technologies have made
      possible to analyze the transcriptional profiles of low abundant cells, such as
      Tfh populations. Using transcriptional signatures, we review here the impact of
      chronic SIV/HIV infection on Tfh, GC Tfh, pTfh, and cTfh differentiation and
      helper T cell functions with regard to their capacity to induce efficient B cell
      maturation. We will explore some hypothesis to explain the increased proportion
      of Tfh cells reported in chronically infected individuals and the impact on HIV
      pathogenesis.

PMID- 27891127
TI  - Regulation of Chemokine Activity - A Focus on the Role of Dipeptidyl Peptidase
      IV/CD26.
AB  - Chemokines are small, chemotactic proteins that play a crucial role in leukocyte
      migration and are, therefore, essential for proper functioning of the immune
      system. Chemokines exert their chemotactic effect by activation of chemokine
      receptors, which are G protein-coupled receptors (GPCRs), and interaction with
      glycosaminoglycans (GAGs). Furthermore, the exact chemokine function is modulated
      at the level of posttranslational modifications. Among the different types of
      posttranslational modifications that were found to occur in vitro and in vivo,
      i.e., proteolysis, citrullination, glycosylation, and nitration, NH2-terminal
      proteolysis of chemokines has been described most intensively. Since the NH2
      terminal chemokine domain mediates receptor interaction, NH2-terminal
      modification by limited proteolysis or amino acid side chain modification can
      drastically affect their biological activity. An enzyme that has been shown to
      provoke NH2-terminal proteolysis of various chemokines is dipeptidyl peptidase IV
      or CD26. This multifunctional protein is a serine protease that preferably
      cleaves dipeptides from the NH2-terminal region of peptides and proteins with a
      proline or alanine residue in the penultimate position. Various chemokines
      possess such a proline or alanine residue, and CD26-truncated forms of these
      chemokines have been identified in cell culture supernatant as well as in body
      fluids. The effects of CD26-mediated proteolysis in the context of chemokines
      turned out to be highly complex. Depending on the chemokine ligand, loss of these
      two NH2-terminal amino acids can result in either an increased or a decreased
      biological activity, enhanced receptor specificity, inactivation of the chemokine
      ligand, or generation of receptor antagonists. Since chemokines direct leukocyte
      migration in homeostatic as well as pathophysiologic conditions, CD26-mediated
      proteolytic processing of these chemotactic proteins may have significant
      consequences for appropriate functioning of the immune system. After introducing
      the chemokine family together with the GPCRs and GAGs, as main interaction
      partners of chemokines, and discussing the different forms of posttranslational
      modifications, this review will focus on the intriguing relationship of
      chemokines with the serine protease CD26.

PMID- 27891134
TI  - Cucumber (Cucumis sativus L.) Nitric Oxide Synthase Associated Gene1 (CsNOA1)
      Plays a Role in Chilling Stress.
AB  - Nitric oxide (NO) is a gaseous signaling molecule in plants, transducing
      information as a result of exposure to low temperatures. However, the underlying
      molecular mechanism linking NO with chilling stress is not well understood. Here,
      we functionally characterized the cucumber (Cucumis sativus L.) nitric oxide
      synthase-associated gene, NITRIC OXIDE ASSOCIATED 1 (CsNOA1). Expression analysis
      of CsNOA1, using quantitative real-time PCR, in situ hybridization, and a
      promoter::beta-glucuronidase (GUS) reporter assay, revealed that it is expressed
      mainly in the root and shoot apical meristem (SAM), and that expression is up
      regulated by low temperatures. A CsNOA1-GFP fusion protein was found to be
      localized in the mitochondria, and ectopic expression of CsNOA1 in the A.
      thaliana noa1 mutant partially rescued the normal phenotype. When overexpressing
      CsNOA1 in the Atnoa1 mutant under normal condition, no obvious phenotypic
      differences was observed between its wild type and transgenic plants. However,
      the leaves from mutant plant grown under chilling conditions showed hydrophanous
      spots and wilting. Physiology tolerance markers, chlorophyll fluorescence
      parameter (Fv/Fm), and electrolyte leakage, were observed to dramatically change,
      compared mutant to overexpressing lines. Transgenic cucumber plants revealed that
      the gene is required by seedlings to tolerate chilling stress: constitutive over
      expression of CsNOA1 led to a greater accumulation of soluble sugars, starch, and
      an up-regulation of Cold-regulatory C-repeat binding factor3 (CBF3) expression as
      well as a lower chilling damage index (CI). Conversely, suppression of CsNOA1
      expression resulted in the opposite phenotype and a reduced NO content compared
      to wild type plants. Those results suggest that CsNOA1 regulates cucumber
      seedlings chilling tolerance. Additionally, under normal condition, we took
      several classic inhibitors to perform, and detect endogenous NO levels in wild
      type cucumber seedling. The results suggest that generation of endogenous NO in
      cucumber leaves occurs largely independently in the (CsNOA1) and nitrate
      reductase (NR) pathway.

PMID- 27891135
TI  - ROS-Mediated Inhibition of S-nitrosoglutathione Reductase Contributes to the
      Activation of Anti-oxidative Mechanisms.
AB  - Nitric oxide (NO) has emerged as a signaling molecule in plants being involved in
      diverse physiological processes like germination, root growth, stomata closing
      and response to biotic and abiotic stress. S-nitrosoglutathione (GSNO) as a
      biological NO donor has a very important function in NO signaling since it can
      transfer its NO moiety to other proteins (trans-nitrosylation). Such trans
      nitrosylation reactions are equilibrium reactions and depend on GSNO level. The
      breakdown of GSNO and thus the level of S-nitrosylated proteins are regulated by
      GSNO-reductase (GSNOR). In this way, this enzyme controls S-nitrosothiol levels
      and regulates NO signaling. Here we report that Arabidopsis thaliana GSNOR
      activity is reversibly inhibited by H2O2in vitro and by paraquat-induced
      oxidative stress in vivo. Light scattering analyses of reduced and oxidized
      recombinant GSNOR demonstrated that GSNOR proteins form dimers under both
      reducing and oxidizing conditions. Moreover, mass spectrometric analyses revealed
      that H2O2-treatment increased the amount of oxidative modifications on Zn2+
      coordinating Cys47 and Cys177. Inhibition of GSNOR results in enhanced levels of
      S-nitrosothiols followed by accumulation of glutathione. Moreover, transcript
      levels of redox-regulated genes and activities of glutathione-dependent enzymes
      are increased in gsnor-ko plants, which may contribute to the enhanced resistance
      against oxidative stress. In sum, our results demonstrate that reactive oxygen
      species (ROS)-dependent inhibition of GSNOR is playing an important role in
      activation of anti-oxidative mechanisms to damping oxidative damage and imply a
      direct crosstalk between ROS- and NO-signaling.

PMID- 27891136
TI  - Characterization of Salinity Tolerance of Transgenic Rice Lines Harboring HsCBL8
      of Wild Barley (Hordeum spontanum) Line from Qinghai-Tibet Plateau.
AB  - Rice is more sensitive to salinity, particularly at its early vegetative and
      later productive stages. Wild plants growing in harsh environments such as wild
      barley from Qinghai-Tibet Plateau adapt to the adverse environment with allelic
      variations at the loci responsible for stressful environment, which could be used
      for rice genetic improvement. In this study, we overexpressed HsCBL8 encoding a
      calcium-sensor calcineurin B-like (CBL) protein in rice. The gene was isolated
      from XZ166, a wild-barley (Hordeum spontanum) line originated from Qinghai-Tibet
      Plateau. We found that XZ166 responded to high NaCl concentration (200 mM) with
      more HsCBL8 transcripts than CM72, a cultivated barley line known for salinity
      tolerance. XZ166 is significantly different from CM72 with nucleotide sequences
      at HsCBL8. The overexpression of HsCBL8 in rice resulted in significant
      improvement of water protection in vivo and plasma membrane, more proline
      accumulation, and a reduction of overall Na+ uptake but little change in K+
      concentration in the plant tissues. Notably, HsCBL8 did not act on some genes
      downstream of the rice CBL family genes, suggesting an interesting interaction
      between HsCBL8 and unknown factors to be further investigated.

PMID- 27891137
TI  - A User's View of the Parameters Derived from the Induction Curves of Maximal
      Chlorophyll a Fluorescence: Perspectives for Analyzing Stress.
AB  - Analysis of the fast kinetics of the induction curve of maximal fluorescence
      represents a relatively recent development for chlorophyll a fluorescence
      measurements. The parameters of the so-called JIP-test are exploited by an
      increasingly large community of users to assess plant stress and its
      consequences. We provide here evidence that these parameters are capable to
      distinguish between stresses of different natures or intensities, and between
      stressed plants of different genetic background or at different developmental
      stages at the time of stress. It is, however, important to keep in mind that the
      JIP-test is inherently limited in scope, that it is based on assumptions which
      are not fully validated and that precautions must be taken to ensure that
      measurements are meaningful. Recent advances suggest that some improvements could
      be implemented to increase the reliability of measurements and the pertinence of
      the parameters calculated. We moreover advocate for using the JIP-test in
      combination with other techniques to build comprehensive pictures of plant
      responses to stress.

PMID- 27891138
TI  - Arabidopsis Seed Content QTL Mapping Using High-Throughput Phenotyping: The
      Assets of Near Infrared Spectroscopy.
AB  - Seed storage compounds are of crucial importance for human diet, feed and
      industrial uses. In oleo-proteaginous species like rapeseed, seed oil and protein
      are the qualitative determinants that conferred economic value to the harvested
      seed. To date, although the biosynthesis pathways of oil and storage protein are
      rather well-known, the factors that determine how these types of reserves are
      partitioned in seeds have to be identified. With the aim of implementing a
      quantitative genetics approach, requiring phenotyping of 100s of plants, our
      first objective was to establish near-infrared reflectance spectroscopic (NIRS)
      predictive equations in order to estimate oil, protein, carbon, and nitrogen
      content in Arabidopsis seed with high-throughput level. Our results demonstrated
      that NIRS is a powerful non-destructive, high-throughput method to assess the
      content of these four major components studied in Arabidopsis seed. With this
      tool in hand, we analyzed Arabidopsis natural variation for these four components
      and illustrated that they all displayed a wide range of variation. Finally, NIRS
      was used in order to map QTL for these four traits using seeds from the
      Arabidopsis thaliana Ct-1 * Col-0 recombinant inbred line population. Some QTL co
      localized with QTL previously identified, but others mapped to chromosomal
      regions never identified so far for such traits. This paper illustrates the
      usefulness of NIRS predictive equations to perform accurate high-throughput
      phenotyping of Arabidopsis seed content, opening new perspectives in gene
      identification following QTL mapping and genome wide association studies.

PMID- 27891139
TI  - Regulation of Phytosiderophore Release and Antioxidant Defense in Roots Driven by
      Shoot-Based Auxin Signaling Confers Tolerance to Excess Iron in Wheat.
AB  - Iron (Fe) is essential but harmful for plants at toxic level. However, how wheat
      plants tolerate excess Fe remains vague. This study aims at elucidating the
      mechanisms underlying tolerance to excess Fe in wheat. Higher Fe concentration
      caused morpho-physiological retardation in BR 26 (sensitive) but not in BR 27
      (tolerant). Phytosiderophore and 2-deoxymugineic acid showed no changes in BR 27
      but significantly increased in BR 26 due to excess Fe. Further, expression of
      TaSAMS. TaDMAS1, and TaYSL15 significantly downregulated in BR 27 roots, while
      these were upregulated in BR 26 under excess Fe. It confirms that inhibition of
      phytosiderophore directs less Fe accumulation in BR 27. However, phytochelatin
      and expression of TaPCS1 and TaMT1 showed no significant induction in response to
      excess Fe. Furthermore, excess Fe showed increased catalase, peroxidase, and
      glutathione reductase activities along with glutathione, cysteine, and proline
      accumulation in roots in BR 27. Interestingly, BR 27 self-grafts and plants
      having BR 26 rootstock attached to BR 27 scion had no Fe-toxicity induced adverse
      effect on morphology but showed BR 27 type expressions, confirming that shoot
      derived signal triggering Fe-toxicity tolerance in roots. Finally, auxin
      inhibitor applied with higher Fe concentration caused a significant decline in
      morpho-physiological parameters along with increased TaSAMS and TaDMAS1
      expression in roots of BR 27, revealing the involvement of auxin signaling in
      response to excess Fe. These findings propose that tolerance to excess Fe in
      wheat is attributed to the regulation of phytosiderophore limiting Fe acquisition
      along with increased antioxidant defense in roots driven by shoot-derived auxin
      signaling.

PMID- 27891141
TI  - Editorial: Molecular and Biotechnological Advancements in Hypericum Species.

PMID- 27891140
TI  - Drought and Heat Differentially Affect XTH Expression and XET Activity and Action
      in 3-Day-Old Seedlings of Durum Wheat Cultivars with Different Stress
      Susceptibility.
AB  - Heat and drought stress have emerged as major constraints for durum wheat
      production. In the Mediterranean area, their negative effect on crop productivity
      is expected to be exacerbated by the occurring climate change. Xyloglucan
      endotransglucosylase/hydrolases (XTHs) are chief enzymes in cell wall remodeling,
      whose relevance in cell expansion and morphogenesis suggests a central role in
      stress responses. In this work the potential role of XTHs in abiotic stress
      tolerance was investigated in durum wheat. The separate effects of dehydration
      and heat exposure on XTH expression and its endotransglucosylase (XET) in vitro
      activity and in vivo action have been monitored, up to 24 h, in the apical and
      sub-apical root regions and shoots excised from 3-day-old seedlings of durum
      wheat cultivars differing in stress susceptibility/tolerance. Dehydration and
      heat stress differentially influence the XTH expression profiles and the activity
      and action of XET in the wheat seedlings, depending on the degree of
      susceptibility/tolerance of the cultivars, the organ, the topological region of
      the root and, within the root, on the gradient of cell differentiation. The root
      apical region was the zone mainly affected by both treatments in all assayed
      cultivars, while no change in XET activity was observed at shoot level,
      irrespective of susceptibility/tolerance, confirming the pivotal role of the root
      in stress perception, signaling, and response. Conflicting effects were observed
      depending on stress type: dehydration evoked an overall increase, at least in the
      apical region of the root, of XET activity and action, while a significant
      inhibition was caused by heat treatment in most cultivars. The data suggest that
      differential changes in XET action in defined portions of the root of young durum
      wheat seedlings may have a role as a response to drought and heat stress, thus
      contributing to seedling survival and crop establishment. A thorough
      understanding of the mechanisms underlying these variations could represent the
      theoretical basis for implementing breeding strategies to develop new highly
      productive hybrids adapted to future climate scenarios.

PMID- 27891142
TI  - Genetic Structure and Evolutionary History of Three Alpine Sclerophyllous Oaks in
      East Himalaya-Hengduan Mountains and Adjacent Regions.
AB  - The East Himalaya-Hengduan Mountains (EH-HM) region has a high biodiversity and
      harbors numerous endemic alpine plants. This is probably the result of combined
      orographic and climate oscillations occurring since late Tertiary. Here, we
      determined the genetic structure and evolutionary history of alpine oak species
      (including Quercus spinosa, Quercus aquifolioides, and Quercus rehderiana) using
      both cytoplasmic-nuclear markers and ecological niche models (ENMs), and
      elucidated the impacts of climate oscillations and environmental heterogeneity on
      their population demography. Our results indicate there were mixed genetic
      structure and asymmetric contemporary gene flow within them. The ENMs revealed a
      similar demographic history for the three species expanded their ranges from the
      last interglacial (LIG) to the last glacial maximum (LGM), which was consistent
      with effective population sizes changes. Effects of genetic drift and
      fragmentation of habitats were responsible for the high differentiation and the
      lack of phylogeographic structure. Our results support that geological and
      climatic factors since Miocene triggered the differentiation, evolutionary origin
      and range shifts of the three oak species in the studied area and also emphasize
      that a multidisciplinary approach combining molecular markers, ENMs and
      population genetics can yield deep insights into diversification and evolutionary
      dynamics of species.

PMID- 27891143
TI  - Comparative Physiological and Proteomic Analysis Reveal Distinct Regulation of
      Peach Skin Quality Traits by Altitude.
AB  - The role of environment in fruit physiology has been established; however,
      knowledge regarding the effect of altitude in fruit quality traits is still
      lacking. Here, skin tissue quality characters were analyzed in peach fruit (cv.
      June Gold), harvested in 16 orchards located in low (71.5 m mean), or high (495 m
      mean) altitutes sites. Data indicated that soluble solids concentration and fruit
      firmness at commercial harvest stage were unaffected by alitute. Peach grown at
      high-altitude environment displayed higher levels of pigmentation and specific
      antioxidant-related activity in their skin at the commercial harvest stage. Skin
      extracts from distinct developmental stages and growing altitudes exhibited
      different antioxidant ability against DNA strand-scission. The effects of
      altitude on skin tissue were further studied using a proteomic approach. Protein
      expression analysis of the mature fruits depicted altered expression of 42
      proteins that are mainly involved in the metabolic pathways of defense, primary
      metabolism, destination/storage and energy. The majority of these proteins were
      up-regulated at the low-altitude region. High-altitude environment increased the
      accumulation of several proteins, including chaperone ClpC, chaperone ClpB,
      pyruvate dehydrogenase E1, TCP domain class transcription factor, and
      lipoxygenase. We also discuss the altitude-affected protein variations, taking
      into account their potential role in peach ripening process. This study provides
      the first characterization of the peach skin proteome and helps to improve our
      understanding of peach's response to altitude.

PMID- 27891144
TI  - A Developmental and Molecular View of Formation of Auxin-Induced Nodule-Like
      Structures in Land Plants.
AB  - Several studies have shown that plant hormones play important roles during legume
      rhizobia symbiosis. For instance, auxins induce the formation of nodule-like
      structures (NLSs) on legume roots in the absence of rhizobia. Furthermore, these
      NLS can be colonized by nitrogen-fixing bacteria, which favor nitrogen fixation
      compared to regular roots and subsequently increase plant yield. Interestingly,
      auxin also induces similar NLS in cereal roots. While several genetic studies
      have identified plant genes controlling NLS formation in legumes, no studies have
      investigated the genes involved in NLS formation in cereals. In this study, first
      we established an efficient experimental system to induce NLS in rice roots,
      using auxin, 2,4-D, consistently at a high frequency (>90%). We were able to
      induce NLS at a high frequency in Medicago truncatula under similar conditions.
      NLS were characterized by a broad base, a diffuse meristem, and increased cell
      differentiation in the vasculature. Interestingly, NLS formation appeared very
      similar in both rice and Medicago, suggesting a similar developmental program. We
      show that NLS formation in both rice and Medicago occurs downstream of the common
      symbiotic pathway. Furthermore, NLS formation occurs downstream of cytokinin
      induced step(s). We performed a comprehensive RNA sequencing experiment to
      identify genes differentially expressed during NLS formation in rice and
      identified several promising genes for control of NLS based on their biological
      and molecular functions. We validated the expression patterns of several genes
      using reverse transcription polymerase chain reaction and show varied expression
      patterns of these genes during different stages of NLS formation. Finally, we
      show that NLS induced on rice roots under these conditions can be colonized by
      nitrogen-fixing bacteria, Azorhizobium caulinodans.

PMID- 27891146
TI  - A Self-Organizing Incremental Spatiotemporal Associative Memory Networks Model
      for Problems with Hidden State.
AB  - Identifying the hidden state is important for solving problems with hidden state.
      We prove any deterministic partially observable Markov decision processes (POMDP)
      can be represented by a minimal, looping hidden state transition model and
      propose a heuristic state transition model constructing algorithm. A new
      spatiotemporal associative memory network (STAMN) is proposed to realize the
      minimal, looping hidden state transition model. STAMN utilizes the neuroactivity
      decay to realize the short-term memory, connection weights between different
      nodes to represent long-term memory, presynaptic potentials, and synchronized
      activation mechanism to complete identifying and recalling simultaneously.
      Finally, we give the empirical illustrations of the STAMN and compare the
      performance of the STAMN model with that of other methods.

PMID- 27891145
TI  - Contrasting Proteomic and Metabolomic Responses of Bermudagrass to Drought and
      Salt Stresses.
AB  - Bermudagrass (Cynodon dactylon) is one of tolerant grass species to drought and
      salt. The comparative analyses of bermudagrass in response to drought and salt
      stresses at the physiological, proteomic, and metabolomic levels were performed
      in this study. The physiological results indicated that osmolytes accumulation,
      ROS level and antioxidant enzyme activities were extensively changed by drought
      and salt stresses. Through comparative proteomic analyses, we successfully
      identified a total of 77 proteins involved in photosynthesis, oxidative pentose
      phosphate, glycolysis, and redox metabolic pathways when exposed to drought and
      salt stresses. Among them, 36 proteins were commonly regulated by both
      treatments, while other 40 and 13 proteins were specifically regulated by drought
      and salt, respectively. Totally 15 proteins were involved in carbon metabolic
      pathway. Moreover, contents of 37 metabolites including amino acids, organic
      acids, sugars, and sugar alcohols were regulated by drought and salt treatments.
      Among them, 18 commonly modulated metabolites were involved in carbon and amino
      acid metabolic pathways. Drought treatment for 21 days caused less accumulation
      of sugars and sugar alcohols and increased ROS level in bermudagrass which led to
      relatively more severe cell membrane reflected by high EL-value and lower
      survival rate when compared to 400 mM salt treatment for 21 days. These results
      suggested that drought and 400 mM NaCl stresses for 21 days treatment affected
      common and specific changes in bermudagrass, which would provide new insights to
      understand the underlying molecular mechanisms and metabolic homeostasis of
      bermudagrass in responses to abiotic stresses.

PMID- 27891147
TI  - Effect of Neoadjuvant Chemoradiotherapy with Capecitabine versus Fluorouracil for
      Locally Advanced Rectal Cancer: A Meta-Analysis.
AB  - A meta-analysis was carried out to compare the efficacy and safety of
      capecitabine plus radiation with 5-fluorouracil (5-FU) plus radiotherapy (RT) as
      neoadjuvant treatment in locally advanced rectal cancer (LARC). We searched the
      Cochrane database, Ovid, Medline, Embase, ISI databases, and Chinese Biomedical
      Literature Database between January 1998 and October 2014. Trials of capecitabine
      compared with 5-FU plus RT as neoadjuvant treatment for LARC were considered for
      inclusion. RevMan software was used to analyze these data. Nine trials were
      included in this meta-analysis, which covered a total of 3141 patients. The meta
      analysis showed that capecitabine group had statistically significant better pCR
      rates (OR, 1.34; 95% CI, 1.10-1.64; P = 0.003), T downstaging rates (OR, 1.58;
      95% CI, 1.22-2.06; P = 0.0007), N downstaging rates (OR, 2.06; 95% CI, 1.34-3.16;
      P = 0.001), less distant metastasis (OR, 0.63; 95% CI, 0.44-0.88; P = 0.007), and
      lowered leucocytes (OR, 0.25; 95% CI, 0.11-0.54; P = 0.0005), but with higher
      incidence of hand-foot syndrome (HFS) (OR, 4.43; 95% CI, 1.59-12.33; P = 0.004).
      Capecitabine was more efficient than 5-FU in terms of tumor response in
      neoadjuvant treatment for patients with LARC and favourably low toxicity with the
      exception of HFS.

PMID- 27891149
TI  - Corynebacterium propinquum: A Rare Cause of Prosthetic Valve Endocarditis.
AB  - Nondiphtheria Corynebacterium species are often dismissed as culture
      contaminants, but they have recently become increasingly recognized as pathologic
      organisms. We present the case of a 48-year-old male patient on chronic
      prednisone therapy for rheumatoid arthritis with a history of mitral valve
      replacement with prosthetic valve. He presented with fever, dizziness, dyspnea on
      exertion, intermittent chest pain, and palpitations. Transesophageal
      echocardiography revealed two medium-sized densities along the inner aspect of
      the sewing ring and one larger density along the atrial surface of the sewing
      ring consistent with vegetation. Two separate blood cultures grew Corynebacterium
      propinquum, which were sensitive to ceftriaxone but highly resistant to
      vancomycin and daptomycin. The patient completed a course of ceftriaxone and
      repeat TEE study and after 6 weeks demonstrated near complete resolution of the
      vegetation. To our knowledge, this case represents the first in the literature of
      Corynebacterium propinquum causing prosthetic valve endocarditis. The ability of
      these organisms to cause deep-seated systemic infections should be recognized,
      especially in immune-compromised patients.

PMID- 27891148
TI  - Can We Accurately Time the Administration of Antenatal Corticosteroids for
      Preterm Labor?
AB  - Background. Accurate timing of antenatal corticosteroids (ACS) has resulted in
      improved neonatal outcomes. Objectives. Our primary objective was to determine
      predictors for optimal timing of ACS in women presenting with spontaneous preterm
      labor. Study Design. A retrospective cohort study of women receiving ACS for
      spontaneous preterm birth was conducted. Women were included if they presented
      with preterm labor or preterm premature rupture of membranes. Accurate timing of
      ACS was defined as administration within 7 days of delivery. Maternal demographic
      and obstetrics characteristics were compared between the groups receiving ACS <=7
      days and >7 days from delivery. Statistical analyses were performed using
      parametric and nonparametric tests. P < 0.05 was considered significant. Results.
      The study included 215 subjects. Median latency from ACS administration to
      delivery was 6 days (IQR 32). Accurate timing of ACS occurred in 113 (53%) women
      and was associated with rupture of membranes (OR 13.8, 95% CI 5.9-32.6), cervical
      change (OR 7.1, 95% CI 3.0-17.1), and cervical dilation >= 2 cm (OR 3.9, 95% CI
      1.5-10.3). Conclusions. Rupture of membranes, cervical change, and cervical
      dilation >= 2 cm were strong predictors of optimal timing. 53% of women with
      preterm labor received ACS optimally.

PMID- 27891150
TI  - Splenic Artery Embolization for the Treatment of Gastric Variceal Bleeding
      Secondary to Splenic Vein Thrombosis Complicated by Necrotizing Pancreatitis:
      Report of a Case.
AB  - Splenic vein thrombosis is a relatively common finding in pancreatitis. Gastric
      variceal bleeding is a life-threatening complication of splenic vein thrombosis,
      resulting from increased blood flow to short gastric vein. Traditionally,
      splenectomy is considered the treatment of choice. However, surgery in
      necrotizing pancreatitis is dangerous, because of severe inflammation, adhesion,
      and bleeding tendency. In the Warshaw operation, gastric variceal bleeding is
      rare, even though splenic vein is resected. Because the splenic artery is also
      resected, blood flow to short gastric vein is not increased problematically.
      Herein, we report a case of gastric variceal bleeding secondary to splenic vein
      thrombosis complicated by necrotizing pancreatitis successfully treated with
      splenic artery embolization. Splenic artery embolization could be the best
      treatment option for gastric variceal bleeding when splenectomy is difficult such
      as in case associated with severe acute pancreatitis or associated with severe
      adhesion or in patients with high operation risk.

PMID- 27891151
TI  - Giant Coronary Artery Aneurysm Causing Acute Anterior Myocardial Infarction.
AB  - A 70-year-old man with hypertension was admitted to our coronary ICU with acute
      anterior MI. Emergent primary PCI was planned and coronary angiography was
      performed. LAD artery was totally occluded in the proximal segment just after a
      huge 32 * 26 mm sized aneurysm. Emergent CABG operation was performed in 75
      minutes because of multivessel disease including the RCA and left circumflex
      artery. Aneurysm was ligated and coronary bypass was performed using LIMA and
      saphenous grafts. The postoperative course of the patient was uneventful. He was
      discharged with medical therapy including ASA, clopidogrel, and atorvastatin. He
      was asymptomatic at his polyclinic visit in the first month.

PMID- 27891152
TI  - Venipuncture Induced Complex Regional Pain Syndrome Presenting as Inflammatory
      Arthritis.
AB  - Venipuncture is one of the most commonly done medical procedures. We report a
      unique case of a 23-year-old young male who presented with features suggestive of
      inflammatory arthritis. The symptoms, which initially started on the right side,
      also involved the other side after a few weeks. Although the patient's symptoms
      and signs were simulating inflammatory arthritis, he had atypical features like
      poor response to anti-inflammatory medicines and normal laboratory parameters.
      His musculoskeletal ultrasonography was also not suggestive of arthritis. His
      history was reviewed and on direct questioning he revealed a history of
      venipuncture for blood sample withdrawal, done from right antecubital region for
      routine health check on the day prior to the onset of symptoms. Complex regional
      pain syndrome was suspected and triple-phase radioisotope bone scan was done
      which was highly suggestive of this diagnosis. The patient was managed with
      multidimensional approach and responded very well to the treatment. Complex
      regional pain syndrome is usually not thought of in the initial differential
      diagnosis of inflammatory arthritis. In this report we highlight the need to
      elicit the often overlooked history of trivial trauma like venipuncture,
      especially in atypical cases of arthritis. Also the role of newer diagnostic
      modalities in such cases is emphasized.

PMID- 27891153
TI  - PAHs Target Hematopoietic Linages in Bone Marrow through Cyp1b1 Primarily in
      Mesenchymal Stromal Cells but Not AhR: A Reconstituted In Vitro Model.
AB  - 7,12-Dimethylbenz(a)anthracene (DMBA) rapidly suppresses hematopoietic
      progenitors, measured as colony forming units (CFU), in mouse bone marrow (BM)
      leading to mature cell losses as replenishment fails. These losses are mediated
      by Cyp1b1, independent of the AhR, despite induction of Cyp1b1. BM mesenchymal
      progenitor cells (MPC) may mediate these responses since basal Cyp1b1 is
      minimally induced. PreB colony forming unit activity (PreB CFU) is lost within 24
      hours in isolated BM cells (BMC) unless cocultured with cells derived from
      primary MPC (BMS2 line). The mouse embryonic OP9 line, which provides more
      efficient coculture support, shares similar induction-resistant Cyp1b1
      characteristics. This OP9 support is suppressed by DMBA, which is then prevented
      by Cyp1b1 inhibitors. OP9-enriched medium partially sustains CFU activities but
      loses DMBA-mediated suppression, consistent with mediation by OP9 Cyp1b1. PreB
      CFU activity in BMC from Cyp1b1-ko mice has enhanced sensitivity to DMBA. BMC
      gene expression profiles identified cytokines and developmental factors that are
      substantially changed in Cyp1b1-ko mice. DMBA had few effects in WT mice but
      systematically modified many clustered responses in Cyp1b1-ko mice. Typical BMC
      AhR-responsive genes were insensitive to Cyp1b1 deletion. TCDD replicated Cyp1b1
      interventions, suggesting alternative AhR mediation. Cyp1b1 also diminishes
      oxidative stress, a key cause of stem cell instability.

PMID- 27891155
TI  - Rabson Mendenhall Syndrome caused by a novel missense mutation.
AB  - BACKGROUND: Rabson Mendenhall syndrome is a rare endocrine condition
      characterized by severe insulin resistance and hyperglycemia. It occurs due to
      mutations in the insulin receptor gene. Few mutations which are associated with
      Rabson Mendenhall syndrome have been identified and reported in the past. The
      management of this condition is extremely challenging and will need multi
      disciplinary approach. CASE PRESENTATION: An 11 year old boy presented with
      polyuria and polydipsia. He was noted to have coarse facies, severe acanthosis
      nigricans, hypertrichosis, retarded growth and developmental delay.
      Investigations revealed severe hyperglycemia which was poorly responsive to high
      doses of insulin. A diagnosis of Rabson Mendenhall syndrome was suspected based
      on his physical characteristics in the presence of insulin resistance. Genetic
      studies revealed a homozygous missense mutation in the Insulin receptor gene
      confirming the diagnosis of Rabson Mendenhall syndrome. This is a novel mutation
      which has not been reported previously. CONCLUSION: Rabson Mendenhall syndrome
      should be suspected in a patient with characteristic physical features, severe
      hyperglycemia and insulin resistance. The genetic studies will not only confirm
      the diagnosis but also will help in counselling. Wider collaboration is needed to
      identify definitive treatment options for managing this rare condition.

PMID- 27891154
TI  - Preparation of Ecofriendly Formulations Containing Biologically Active
      Monoterpenes with Their Fumigant and Residual Toxicities against Adults of Culex
      pipiens.
AB  - Different mixtures of monoterpenes (ketone, alcohol, and alkene) were loaded on
      paper discs and wax and their knockdown activities were evaluated against Culex
      pipiens adults. Some individual monoterpenes were also evaluated by residual
      toxicity technique. Citronella oil as a reference was also loaded separately or
      in combination with monoterpenes on paper discs and wax. The ketone monoterpenes
      mixture (camphor, menthone, carvone, and fenchone) on paper discs was the most
      active (KT50 = 17.20 min) followed by ketone monoterpenes with citronella oil
      (KT50 = 20.79 min) and citronella oil alone (KT50 = 28.72 min). Wax formulations
      proved that the ketone and alcohol (geraniol, thymol, and menthol) monoterpenes
      gave the most activity as knockdown (KT50 = 31.79 and 43.39 min, resp.). Alcohol
      monoterpenes formulation recorded KT50 = 43.39 min. Residual activity of tested
      individual monoterpenes reported that the menthol was more toxic than camphor and
      camphene. Generally, this study suggests that the monoterpenes have the
      properties, which make them used as eco-friendly compounds in the control
      programs of Cx. pipiens adult. The use of paper discs is more applicable than wax
      in the adulticidal formulations.

PMID- 27891156
TI  - Usefulness of component resolved analysis of cat allergy in routine clinical
      practice.
AB  - BACKGROUND: Cat allergy is of great importance, and its prevalence is increasing
      worldwide. Cat allergens and house dust mite allergens represent the major indoor
      allergens; however, they are ubiquitous. Cat sensitization and allergy are known
      risk factors for rhinitis, bronchial hyperreactivity and asthma. Thus, the
      diagnosis of sensitization to cats is important for any allergist. METHODS: 70
      patients with positive skin prick tests for cats were retrospectively compared
      regarding their skin prick test results, as well as their specific immunoglobulin
      E antibody profiles with regard to their responses to the native cat extract,
      rFel d 1, nFel d 2 and rFel d 4. 35 patients were allergic to cats, as determined
      by positive anamnesis and/or nasal provocation with cat allergens, and 35
      patients exhibited clinically non-relevant sensitization, as indicated by
      negative anamnesis and/or a negative nasal allergen challenge. RESULTS: Native
      cat extract serology testing detected 100% of patients who were allergic to cats
      but missed eight patients who showed sensitization in the skin prick test and did
      not have allergic symptoms. The median values of the skin prick test, as well as
      those of the specific immunoglobulin E antibodies against the native cat extract,
      were significantly higher for allergic patients than for patients with clinically
      non-relevant sensitization. Component based diagnostic testing to rFel d 1 was
      not as reliable. Sensitization to nFel d 2 and rFel d 4 was seen only in
      individual patients. CONCLUSION: Extract based diagnostic methods for identifying
      cat allergy and sensitization, such as the skin prick test and native cat extract
      serology, remain crucial in routine clinical practice. In our study, component
      based diagnostic testing could not replace these methods with regard to the
      detection of sensitization to cats and differentiation between allergy and
      sensitization without clinical relevance. However, component resolved allergy
      diagnostic tools have individual implications, and future studies may facilitate
      a better understanding of its use and subsequently may improve the clinical
      management of allergic patients.

PMID- 27891158
TI  - Natural Active Ingredients for Diabetes and Metabolism Disorders Treatment.

PMID- 27891157
TI  - The In Vitro Antimicrobial Effects of Lavandula angustifolia Essential Oil in
      Combination with Conventional Antimicrobial Agents.
AB  - The paper focuses on the in vitro antimicrobial activity of Lavandula
      angustifolia Mill. (lavender) essential oil in combination with four commercial
      antimicrobial agents. Stock solutions of chloramphenicol, ciprofloxacin,
      nystatin, and fusidic acid were tested in combination with L. angustifolia
      essential oil. The antimicrobial activities of the combinations were investigated
      against the Gram-positive bacterial strain Staphylococcus aureus (ATCC 6538) and
      Gram-negative Pseudomonas aeruginosa (ATCC 27858) and Candida albicans (ATCC
      10231) was selected to represent the yeasts. The antimicrobial effect was
      performed using the minimum inhibitory concentration (MIC) microdilution assay.
      Isobolograms were constructed for varying ratios. The most prominent interaction
      was noted when L. angustifolia essential oil was combined with chloramphenicol
      and tested against the pathogen P. aeruginosa (SigmaFIC of 0.29). Lavendula
      angustifolia essential oil was shown in most cases to interact synergistically
      with conventional antimicrobials when combined in ratios where higher volumes of
      L. angustifolia essential oil were incorporated into the combination.

PMID- 27891159
TI  - Effects of Health Qigong Exercises on Relieving Symptoms of Parkinson's Disease.
AB  - The purpose of this study was to investigate the effects of Health Qigong on the
      treatment and releasing symptoms of Parkinson's disease (PD). Fifty-four moderate
      PD patients (N = 54) were randomly divided into experimental and control groups.
      Twenty-eight PD patients were placed in the experimental group in which the
      prescribed medication plus Health Qigong exercise will be used as intervention.
      The other 26 PD patients as the control group were treated only with regular
      medication. Ten-week intervention had been conducted for the study, and
      participants completed the scheduled exercises 5 times per week for 60 minutes
      each time (10 minutes for warm-up, 40 minutes for the exercise, and 10 minutes
      for cooldown). Data which included the muscle hardness, one-legged blind balance,
      physical coordination, and stability was collected before, during, and after the
      intervention. Comparisons were made between the experimental and control groups
      through the Repeated Measures ANOVA. The results showed that PD patients
      demonstrate a significant improvement in muscle hardness, the timed "up and go,"
      balance, and hand-eye coordination (the turn-over-jars test). There were no
      significant differences between the two groups in gender, age, and course of
      differences (P < 0.05). The study concluded that Health Qigong exercises could
      reduce the symptoms of Parkinson's disease and improve the body functions of PD
      patients in both the mild and moderate stages. It can be added as an effective
      treatment of rehabilitation therapy for PD.

PMID- 27891160
TI  - HIV sero-discordance among married HIV patients initiating anti-retroviral
      therapy in northern Vietnam.
AB  - BACKGROUND: In many countries in Asia, the HIV epidemic is in a concentrated
      phase, with high prevalence in certain risk groups, such as men who inject drugs.
      There is also a rapid increase of HIV among women. The latter might be due to
      high levels of sero-discordant couples and increasing transmission from male to
      female partners over time. METHODS: All adult married patients initiating
      antiretroviral treatment at four out-patient clinics in Quang Ninh province in
      north-eastern Vietnam between 2007 and 2009 were asked to participate in the
      study. Clinical information was extracted from patients' records, and a
      structured questionnaire was used to collect social, demographic and economic
      data. RESULTS: Two hundred eighty-eight married patients for whom information on
      the HIV status of their spouse was available were included in the study. Overall,
      the sero-discordance rate was 58%. The sero-discordance rate was significantly
      higher among married males, 71% had spouses not infected, than married females,
      of whom 18% had spouses not infected. Other factors associated with a high rate
      of sero-discordance were injection drug use (IDU) history, tuberculosis (TB)
      history and the availability of voluntary counselling and testing (VCT) in
      residential locations. High sero-concordance was associated with
      college/university education. CONCLUSION: The sero-discordance was significantly
      higher among married males than married females. Other factors also related to
      high sero-discordance were history of IDU, history of TB and the availability of
      VCT in residential locations. In contrast, college/university education and
      female sex were significantly related to low sero-discordance. To contain the
      increasing HIV prevalence among women, measures should be taken to prevent
      transmission among sero-discordant couples. Trial registration NCT01433601.

PMID- 27891162
TI  - Nutrition surveillance using a small open cohort: experience from Burkina Faso.
AB  - BACKGROUND: Nutritional surveillance remains generally weak and early warning
      systems are needed in areas with high burden of acute under-nutrition. In order
      to enhance insight into nutritional surveillance, a community-based sentinel
      sites approach, known as the Listening Posts (LP) Project, was piloted in Burkina
      Faso by Action Contre la Faim (ACF). This paper presents ACF's experience with
      the LP approach and investigates potential selection and observational biases.
      METHODS: Six primary sampling units (PSUs) were selected in each livelihood zone
      using the centric systematic area sampling methodology. In each PSU, 22 children
      aged between 6 and 24 months were selected by proximity sampling. The prevalence
      of GAM for each month from January 2011 to December 2013 was estimated using a
      Bayesian normal-normal conjugate analysis followed by PROBIT estimation. To
      validate the LP approach in detecting changes over time, the time trends of MUAC
      from LP and from five cross-sectional surveys were modelled using polynomial
      regression and compared by using a Wald test. The differences between prevalence
      estimates from the two data sources were used to assess selection and
      observational biases. RESULTS: The 95 % credible interval around GAM prevalence
      estimates using LP approach ranged between +6.5 %/-6.0 % on a prevalence of 36.1
      % and +3.5 %/-2.9 % on a prevalence of 10.8 %. LP and cross-sectional surveys
      time trend models were well correlated (p = 0.6337). Although LP showed a slight
      but significant trend for GAM to decrease over time at a rate of -0.26 %/visit,
      the prevalence estimates from the two data sources showed good agreement over a 3
      year period. CONCLUSIONS: The LP methodology has proved to be valid in following
      trends of GAM prevalence for a period of 3 years without selection bias. However,
      a slight observational bias was observed, requiring a periodical reselection of
      the sentinel sites. This kind of surveillance project is suited to use in areas
      with high burden of acute under-nutrition where early warning systems are
      strongly needed. Advocacy is necessary to develop sustainable nutrition
      surveillance system and to support the use of surveillance data in guiding
      nutritional programs.

PMID- 27891161
TI  - Cases of antiretroviral-associated gynaecomastia reported to the National HIV &
      Tuberculosis Health Care Worker Hotline in South Africa.
AB  - BACKGROUND: Gynaecomastia is associated with exposure to antiretroviral therapy
      (ART), in particular efavirenz. There is limited data on clinical characteristics
      of patients with ART-associated gynaecomastia in resource-limited settings and
      little guidance on the optimal management of this adverse drug reaction (ADR). We
      describe the clinical characteristics, management and outcomes of gynaecomastia
      cases reported to the National HIV & Tuberculosis Health Care Worker Hotline in
      South Africa. METHODS: We identified all gynaecomastia cases in adolescent boys
      and men on ART reported to the hotline between June 2013 and July 2014. We
      collected follow up data telephonically at monthly intervals to document clinical
      management and outcomes. RESULTS: We received 51 reports of gynaecomastia between
      June 2013 and July 2014; 11% of the 475 patient-specific ADR queries to the
      hotline. All patients were on efavirenz-based ART. Mean age was 34 years
      (standard deviation 12) and seven were adolescents. The median onset of
      gynaecomastia was 15 months after efavirenz initiation (interquartile range 6
      42). Gynaecomastia was bilateral in 29 patients (57%) and unilateral in 16 (31%).
      Serum testosterone was quantified in 25 of 35 patients with follow up data, and
      was low in 2 (8%). Efavirenz was replaced with an alternative antiretroviral in
      29/35 patients (83%) and gynaecomastia improved in 20/29 (69%). CONCLUSIONS:
      Gynaecomastia was a frequently reported ADR in our setting, occurring with
      prolonged efavirenz exposure. Testosterone was low in the minority of tested
      cases. Most clinicians elected to switch patients off efavirenz, and
      gynaecomastia improved in the majority.

PMID- 27891163
TI  - The visual system of harvestmen (Opiliones, Arachnida, Chelicerata) - a re
      examination.
AB  - BACKGROUND: The visual systems in chelicerates are poorly understood, even though
      they show strong variation in eye and visual neuropil architecture, thus may
      provide valuable insights for the understanding of chelicerate phylogeny and eye
      evolution. Comparable morphological characters are desperately sought for
      reconstructions of the phylogeny of Chelicerata, especially with respect to
      Arachnida. So far, reliable data exist only for Pycnogonida, Xiphosura,
      Scorpiones, and Araneae. The few earlier studies of the organisation of the
      visual system in harvestmen are contradictory concerning the number, morphology,
      and position of the visual neuropils. RESULTS: We undertook a descriptive and
      comparative analysis of the neuroanatomy of the visual system in several
      phalangid harvestmen species. Various traditional and modern methods were used
      that allow comparisons with previous results (cobalt fills, DiI/DiO labelling,
      osmium ethyl gallate procedure, and TEM). The R-cells (photoreceptor and
      arhabdomeric cells) in the eyes of Opiliones are linked to a first and a second
      visual neuropil. The first visual neuropil receives input from all R-cell axons,
      in the second only few R-cells terminate in the distal part. Hence, the second
      visual neuropil is subdivided in a part with direct R-cell input and a part
      without. The arcuate body is located in a subsequent position with direct contact
      to the second visual neuropil. CONCLUSIONS: This re-examination comes to
      conclusions different from those of all previous studies. The visual system of
      phalangid Opiliones occupies an intermediate position between Pycnogonida,
      Xiphosura, and Scorpiones on the one side, and Araneae on the other side. The
      projection of the R-cells is similar to that in the former grouping, the general
      neuropil arrangement to that in the latter taxon. However, more research on the
      visual systems in other chelicerate orders is needed in order to draw inferences
      on phylogeny or eye evolution.

PMID- 27891164
TI  - A low-carbohydrate high-fat diet decreases lean mass and impairs cardiac function
      in pair-fed female C57BL/6J mice.
AB  - BACKGROUND: Excess body fat is a major health issue and a risk factor for the
      development of numerous chronic diseases. Low-carbohydrate diets like the Atkins
      Diet are popular for rapid weight loss, but the long-term consequences remain the
      subject of debate. The Scandinavian low-carbohydrate high-fat (LCHF) diet, which
      has been popular in Scandinavian countries for about a decade, has very low
      carbohydrate content (~5 E %) but is rich in fat and includes a high proportion
      of saturated fatty acids. Here we investigated the metabolic and physiological
      consequences of a diet with a macronutrient composition similar to the
      Scandinavian LCHF diet and its effects on the organs, tissues, and metabolism of
      weight stable mice. METHODS: Female C57BL/6J mice were iso-energetically pair-fed
      for 4 weeks with standard chow or a LCHF diet. We measured body composition using
      echo MRI and the aerobic capacity before and after 2 and 4 weeks on diet. Cardiac
      function was assessed by echocardiography before and after 4 weeks on diet. The
      metabolic rate was measured by indirect calorimetry the fourth week of the diet.
      Mice were sacrificed after 4 weeks and the organ weight, triglyceride levels, and
      blood chemistry were analyzed, and the expression of key ketogenic, metabolic,
      hormonal, and inflammation genes were measured in the heart, liver, and adipose
      tissue depots of the mice using real-time PCR. RESULTS: The increase in body
      weight of mice fed a LCHF diet was similar to that in controls. However, while
      control mice maintained their body composition throughout the study, LCHF mice
      gained fat mass at the expense of lean mass after 2 weeks. The LCHF diet
      increased cardiac triglyceride content, impaired cardiac function, and reduced
      aerobic capacity. It also induced pronounced alterations in gene expression and
      substrate metabolism, indicating a unique metabolic state. CONCLUSIONS: Pair-fed
      mice eating LCHF increased their percentage of body fat at the expense of lean
      mass already after 2 weeks, and after 4 weeks the function of the heart
      deteriorated. These findings highlight the urgent need to investigate the effects
      of a LCHF diet on health parameters in humans.

PMID- 27891166
TI  - Relation of 24-hour urinary caffeine and caffeine metabolite excretions with self
      reported consumption of coffee and other caffeinated beverages in the general
      population.
AB  - BACKGROUND: Caffeine intake is generally estimated by self-reported consumption,
      but it remains unclear how well self-report associates with metabolite urinary
      excretion. We investigated the associations of self-reported consumption of
      caffeinated drinks with urinary excretion of caffeine and its major metabolites
      in an adult population. METHODS: We used data from the population-based Swiss
      Kidney Project on Genes in Hypertension (SKIPOGH) study. Consumption of
      caffeinated coffee, decaffeinated coffee and other caffeinated beverages was
      assessed by self-administered questionnaire. Quantification of caffeine,
      paraxanthine, theobromine and theophylline was performed by ultra-high
      performance liquid chromatography tandem mass spectrometry in 24-h urine.
      Association of reported consumption of caffeinated drinks with urinary caffeine
      derived metabolites was determined by quantile regression. We then explored the
      association between urinary metabolite excretion and dichotomized weekly
      consumption frequency of caffeinated coffee, with Receiver Operator
      Characteristic (ROC) analysis. RESULTS: In the present analysis, we included 598
      individuals (52% women, mean age =46 +/- 17 years). Self-reported caffeinated
      coffee intake was positively associated with 24-h urinary excretions of
      paraxanthine, theophylline and caffeine (p < 0.001), whereas reported intakes of
      decaffeinated coffee and other caffeinated beverages showed no association. In
      ROC analysis, optimal discrimination between individuals consuming less than one
      caffeinated coffee/week, vs. at least one coffee, was obtained for 24-h urinary
      paraxanthine (Area Under Curve (AUC) = 0.868, 95% Confidence Interval (CI)
      [0.830;0.906]), with slightly lower performance for theophylline and caffeine,
      whereas theobromine did not allow any discrimination. CONCLUSION: Our results
      suggest that reported consumption of caffeinated coffee is positively associated
      with 24-h urinary excretion of caffeine, paraxanthine, and theophylline, and may
      be used as a marker of caffeine intake for epidemiological studies.

PMID- 27891165
TI  - Postprandial lipemic and inflammatory responses to high-fat meals: a review of
      the roles of acute and chronic exercise.
AB  - Postprandial lipemia is an independent risk factor for development of
      cardiovascular disease. Postprandial inflammation following the prolonged
      elevation of triglycerides occurring subsequent to ingestion of high-fat meals,
      provides a likely explanation for increased disease risk. Substantial evidence
      has shown that acute exercise is an effective modality for attenuation of
      postprandial lipemia following a high-fat meal. However, much of the evidence
      pertaining to exercise intensity, duration, and overall energy expenditure for
      reducing postprandial lipemia is inconsistent. The effects of these different
      exercise variables on postprandial inflammation is largely unknown. Long-term,
      frequent exercise, however, appears to effectively reduce systemic inflammation,
      especially in at-risk or diseased individuals. With regard to an acute
      postprandial response, without a recent bout of exercise, high levels of chronic
      exercise do not appear to reduce postprandial lipemia. This review summarizes the
      current literature on postprandial and inflammatory responses to high-fat meals,
      and the roles that both acute and chronic exercise play. This review may be
      valuable for health professionals who wish to provide evidence-based, pragmatic
      advice for reducing postprandial lipemia and cardiovascular disease risk for
      their patients. A brief review of proposed mechanisms explaining how high-fat
      meals may result in pro-inflammatory and pro-atherosclerotic environments is also
      included.

PMID- 27891168
TI  - Erratum to: Assessment of Vitamin D status in a group of Egyptian children with
      non alcoholic fatty liver disease (multicenter study).
AB  - [This corrects the article DOI: 10.1186/s12986-016-0112-z.].

PMID- 27891169
TI  - Can procedural and substantive elements of decision-making be reconciled in
      assessments of mental capacity?
AB  - Capacity legislation aims to protect individual autonomy and avoid undue
      paternalism as far as possible, partly through ensuring patients are not deemed
      to lack capacity because they make an unwise decision. To this end, the law
      employs a procedural test of capacity that excludes substantive judgments about
      patients' decisions. However, clinical intuitions about patients' capacity to
      make decisions about their treatment often conflict with a strict reading of the
      legal criteria for assessing capacity, particularly in psychiatry. In this
      article I argue that this tension arises because the procedural conception of
      capacity is inadequate and does not reflect the clinical or legal realities of
      assessing capacity. I propose that conceptualising capacity as having
      'recognisable reasons' for a treatment decision provides a practical way of
      legitimately incorporating both procedural and substantive elements of decision
      making into assessments of capacity.

PMID- 27891167
TI  - Effect on body weight and composition in overweight/obese Australian adults over
      12 months consumption of two different types of fibre supplementation in a
      randomized trial.
AB  - BACKGROUND/OBJECTIVES: Higher fibre intakes are associated with risk reduction
      for chronic diseases. However, many people find difficulty in consuming
      sufficient fibre through their diet. Supplements may be an effective alternative.
      We aimed to investigate the effects of PolyGlycopleX(r) (PGX(r)), a proprietary
      polysaccharide complex and a proprietary Psyllium product (PgxSylTM) (PSY) on
      diet, body weight and composition in overweight and obese individuals.
      SUBJECTS/METHODS: This was a double-blind 52 weeks study with 159 people
      randomized to 3 groups: control (rice flour); PGX (PGX) and proprietary psyllium
      (PSY). Participants did not change any of their usual habits or diet except they
      consumed 5 g of supplement taken with a total of 500 ml of water 5-10 min before
      meals. RESULTS: Weight was significantly lower in the PGX group compared to
      control at 3 (-1.6 kg [0.57, 2.67, p = 0.003]), 6 (-2.6 kg [1.01, 4.13, p =
      0.001]) and 12 months (-2.6 kg [0.59, 4.64, p = 0.012]) and in the PSY group
      compared to control group at 3 (-1.1 kg [0.07, 2.12, p = 0.037]) and 6 months (
      2.4 kg [0.95, 3.93, p = 0.002]). This was a difference of - 2.8% for the PGX
      group and - 1.5% for the PSY group compared to control after 12 months
      supplementation. Body Fat was significantly lower in PGX compared to control at 6
      (-1.8 kg [0.63, 2.95, p = 0.003]) and 12 months (-1.9 kg [0.43, 3.36, p = 0.012])
      and in PSY compared to control at 6 (-1.9 kg [0.84, 3.04, p = 0.001]) and 12
      months (-1.4 kg [0.08, 2.71, p = 0.038]). CONCLUSIONS: PGX was better than PSY at
      maintaining dietary changes and weight loss over the 12 month intervention
      period, with no change to exercise. A simple strategy of PGX supplementation may
      offer an effective solution to long-term weight-loss and then management without
      the need for other nutrient modification. TRIAL REGISTRATION: ANZCTR:
      ACTRN12611000415909. Registered 20 April 2011.

PMID- 27891170
TI  - Prevalence and predictors of musculoskeletal pain among Danish fishermen -
      results from a cross-sectional survey.
AB  - BACKGROUND: Fishermen work in a physically challenging work environment. The aim
      of this analysis was to estimate the prevalence and predictors of musculoskeletal
      pain among Danish fishermen. METHOD: A cross-sectional survey in a random sample
      of Danish fishermen was done with application of the Nordic questionnaire
      regarding musculoskeletal pain considering lower back, shoulders, hand neck,
      knee, upper back elbow, hip and feet. In total, 270 fishermen participated in the
      study (response rate: 28%). Workload, vessel type, skipper, duration of work,
      sideline occupation, days/weeks of fishing at sea, age, BMI and education were
      used as predictors for the overall musculoskeletal pain score (multiple linear
      regression) and for each single pain site ( multinomial logistic regression ).
      RESULTS: The prevalence of pain was high for all musculoskeletal locations.
      Overall, more than 80% of the responding Danish fishermen reported low back pain,
      which in 37% lasted for a minimum of 30 days during the past year. In the
      multiple linear regression analysis, middle workload was associated with a 32%
      (95% CI: 19-46%) and high workload with 60% (95% CI: 46-73%) increased
      musculoskeletal pain score compared to low work load. Multinomial logistic
      regression models showed that workload was the only predictor for all pain sites,
      in particular regarding upper and lower limb pain. CONCLUSION: Although changes
      were implemented to improve the fishermen's work environment, the work continues
      to be physically demanding and impacting their musculoskeletal pain. Potential
      explanation for this unexpected result like increased work pressure and reduced
      financial attractiveness in small scale commercial fishery needs to be confirmed
      in future research.

PMID- 27891171
TI  - A rapid approach to investigate spatiotemporal distribution of phytohormones in
      rice.
AB  - BACKGROUND: Phytohormones play crucial roles in almost all stages of plant growth
      and development. Accurate and simultaneous determination of multiple
      phytohormones enabled us to better understand the physiological functions and the
      regulatory networks of phytohormones. However, simultaneous determination of
      multiple phytohormones in plant is still a challenge due to their low
      concentrations, structural and chemical diversity, and complex matrix of plant
      tissues. Therefore, development of a simple and selective method for the
      simultaneous determination of multiple phytohormones is highly needed. RESULTS:
      We developed a clean-up strategy for profiling of multiple phytohormones, which
      can overcome the challenge of structural and chemical diversity. By using a one
      step dispersive solid-phase extraction (DSPE) combined with UPLC-MS/MS, 54
      phytohormones including auxins, ABA, SA, JA, GAs and CKs were simultaneously
      analyzed from a single rice sample extract. Using the developed method, we
      investigated the spatiotemporal distribution of phytohormones in rice. The
      profiling of various tissues of rice at different growth stages revealed the
      complexity of metabolic regulation and allocations of phytohormone species.
      CONCLUSION: A rapid one-step method was developed for the simultaneous analysis
      of six groups of phytohormones, including cytokinins, auxins, salicylic acid,
      jasmonates, abscisic acid and gibberellins in a single run, using UPLC-ESI-MS/MS.
      The proposed method was successfully applied to investigate spatiotemporal
      distribution of multiple phytohormones in rice. The spatiotemporal information
      obtained may be helpful for better understanding of phytohormones functions
      throughout life cycle of rice when integrated into transcriptome and other omics
      data.

PMID- 27891172
TI  - Vortex Analysis of Intra-Aneurismal Flow in Cerebral Aneurysms.
AB  - This study aims to develop an alternative vortex analysis method by measuring
      structure ofIntracranial aneurysm (IA) flow vortexes across the cardiac cycle, to
      quantify temporal stability of aneurismal flow. Hemodynamics were modeled in
      "patient-specific" geometries, using computational fluid dynamics (CFD)
      simulations. Modified versions of known lambda2 and Q-criterion methods
      identified vortex regions; then regions were segmented out using the classical
      marching cube algorithm. Temporal stability was measured by the degree of vortex
      overlap (DVO) at each step of a cardiac cycle against a cycle-averaged vortex and
      by the change in number of cores over the cycle. No statistical differences exist
      in DVO or number of vortex cores between 5 terminal IAs and 5 sidewall IAs. No
      strong correlation exists between vortex core characteristics and geometric or
      hemodynamic characteristics of IAs. Statistical independence suggests this
      proposed method may provide novel IA information. However, threshold values used
      to determine the vortex core regions and resolution of velocity data influenced
      analysis outcomes and have to be addressed in future studies. In conclusions,
      preliminary results show that the proposed methodology may help give novel
      insight toward aneurismal flow characteristic and help in future risk assessment
      given more developments.

PMID- 27891173
TI  - Laparoscopic cholecystectomy for acute calculous cholecystitis: a retrospective
      study assessing risk factors for conversion and complications.
AB  - BACKGROUND: The purpose of the study was to identify risk factors for conversion
      of laparoscopic cholecystectomy and risk factors for postoperative complications
      in acute calculous cholecystitis. The most common complications arising from
      cholecystectomy were also to be identified. METHODS: A total of 499 consecutive
      patients, who had undergone emergent cholecystectomy with diagnosis of
      cholecystitis in Meilahti Hospital in 2013-2014, were identified from the
      hospital database. Of the identified patients, 400 had acute calculous
      cholecystitis of which 27 patients with surgery initiated as open cholecystectomy
      were excluded, resulting in 373 patients for the final analysis. The Clavien
      Dindo classification of surgical complications was used. RESULTS: Laparoscopic
      cholecystectomy was initiated in 373 patients of which 84 (22.5%) were converted
      to open surgery. Multivariate logistic regression identified C-reactive protein
      (CRP) over 150 mg/l, age over 65 years, diabetes, gangrene of the gallbladder and
      an abscess as risk factors for conversion. Complications were experienced by 67
      (18.0%) patients. Multivariate logistic regression identified age over 65 years,
      male gender, impaired renal function and conversion as risk factors for
      complications. CONCLUSIONS: Advanced cholecystitis with high CRP, gangrene or an
      abscess increase the risk of conversion. The risk of postoperative complications
      is higher after conversion. Early identification and treatment of acute calculous
      cholecystitis might reduce the number of patients with advanced cholecystitis and
      thus improve outcomes.

PMID- 27891174
TI  - Combination of cisplatin and bromelain exerts synergistic cytotoxic effects
      against breast cancer cell line MDA-MB-231 in vitro.
AB  - BACKGROUND: Bromelain, which is a cysteine endopeptidase commonly found in
      pineapple stems, has been investigated as a potential anti-cancer agent for the
      treatment of breast cancer. However, information pertaining to the effects of
      combining bromelain with existing chemotherapeutic drugs remains scarce. This
      study aimed to investigate the possible synergistic cytotoxic effects of using
      bromelain in combination with cisplatin on MDA-MB-231 human breast cancer cells.
      METHOD: MDA-MB-231 cells were treated with different concentrations (0.24-9.5 uM)
      of bromelain or cisplatin alone, as well as four different combinations of these
      two agents to assess their individual and combination effects after 24 and 48 h.
      Cell viability was analyzed using an MTT assay. The induction of apoptosis was
      assessed using cell cycle analysis and an Annexin V-FITC assay. The role of the
      mitochondrial membrane potential in the apoptotic process was assessed using a JC
      1 staining assay. Apoptotic protein levels were assessed by western blot analysis
      and proteome profiling using an antibody array kit. RESULTS: Single-agent
      treatment with cisplatin or bromelain led to dose- and time-dependent decreases
      in the viability of the MDA-MB-231 cells at 24 and 48 h. Furthermore, most of the
      combinations evaluated in this study displayed synergistic effects against MDA-MB
      231 cells at 48 h, with combination 1 (bromelain 2 uM + cisplatin 1.5 uM)
      exhibiting the greatest synergistic effect (P = 0.000). The results of subsequent
      assays indicated that combination 1 treatment induced apoptosis via mitochondria
      mediated pathway. Combination 1 also resulted in significant decreases in the
      levels of several apoptotic proteins such as Bcl-x and HSP70, compared with
      bromelain (P = 0.002 and 0.000, respectively) or cisplatin (P = 0.000 and 0.001,
      respectively) single treatment. Notably, MDA-MB-231 cells treated with
      combination 1 showed increased levels of the pro-apoptotic proteins Bax compared
      with those treated with bromelain (P = 0.000) or cisplatin single treatment (P =
      0.043). CONCLUSION: Bromelain in combination with cisplatin synergistically
      enhanced the induction of apoptosis in MDA-MB-231 cells.

PMID- 27891175
TI  - Multidetector computer tomography in the pancreatic adenocarcinoma assessment: an
      update.
AB  - Ductal adenocarcinoma of the pancreas is one of the most aggressive forms of
      cancer, with only a minority of cases being resectable at the moment of their
      diagnosis. The accurate detection and characterization of pancreatic carcinoma is
      very important for patient management. Multidetector-row computed tomography
      (MDCT) has become the cross-sectional modality of choice in the diagnosis,
      staging, treatment planning, and follow-up of patients with pancreatic tumors.
      However, approximately 11% of ductal adenocarcinomas still remain undetected at
      MDCT because of the lack of attenuation gradient between the lesion and the
      adjacent pancreatic parenchyma. In this systematic literature review we
      investigate the current evolution of the CT technique, limitations, and
      perspectives in the evaluation of pancreatic carcinoma.

PMID- 27891176
TI  - A series of patients with purging type anorexia nervosa who do "tube vomiting".
AB  - BACKGROUND: It is important for clinicians to assess their patients' purging
      behavior. Various methods of purging, such as self-induced vomiting are well
      known. Because patients do not always report their purging behavior, knowing the
      clinical signs that indicate the behavior is useful. However, we have experienced
      patients who did not have the reported physical signs of self-induced vomiting
      because they used hoses instead of their fingers to purge their stomach contents,
      which they call "tube vomiting". No other previous studies have reported the use
      of hoses as a purging tool. CASE PRESENTATION: We present as our main case a 20
      year-old Japanese woman with anorexia nervosa who engaged in "tube vomiting."
      Although she recovered well under medical treatment in our hospital, she began to
      lose weight and blood potassium soon after discharge. We found that she used a
      garden hose instead of her fingers to perform self-induced vomiting,. She
      inserted the hose into her stomach and evacuated the stomach contents through it,
      without pain. She learned this technique through a blog about eating disorders.
      We also present two other similar cases. In fact, many patients discuss "tube
      vomiting" on the internet. CONCLUSION: Our experience suggests that a sudden
      decrease in the weight and blood potassium level could indicate "tube vomiting".
      In addition, because many information resources are available on the internet,
      medical practitioners should be aware of these sites.

PMID- 27891178
TI  - Enrichment of small pathogenic deletions at chromosome 9p24.3 and 9q34.3
      involving DOCK8, KANK1, EHMT1 genes identified by using high-resolution
      oligonucleotide-single nucleotide polymorphism array analysis.
AB  - BACKGROUND: High-resolution oligo-SNP array allowed the identification of
      extremely small pathogenic deletions at numerous clinically relevant regions. In
      our clinical practice, we found that small pathogenic deletions were frequently
      encountered at chromosome 9p and 9q terminal regions. RESULTS: A review of 531
      cases with reportable copy number changes on chromosome 9 revealed142 pathogenic
      copy number variants (CNVs): 104 losses, 31 gains, 7 complex chromosomal
      rearrangements. Of 104 pathogenic losses, 57 were less than 1 Mb in size,
      enriched at 9p24.3 and 9q34.3 regions, involving the DOCK8, KANK1, EHMT1 genes.
      The remaining 47 cases were due to interstitial or terminal deletions larger than
      1 Mb or unbalanced translocations. The small pathogenic deletions of DOCK8, KANK1
      and EHMT1 genes were more prevalent than small pathogenic deletions of NRXN1,
      DMD, SHANK3 genes and were only second to the 16p11.2 deletion syndrome, 593-kb
      (OMIM #611913). CONCLUSIONS: This study corroborated comprehensive genotype
      phenotype large scale studies at 9p24.3 and 9q24.3 regions for a better
      understanding of the pathogenicity caused by haploinsufficiency of the DOCK8,
      KANK1 and EHMT1 genes. TRIAL REGISTRATION NUMBER: None; it is not a clinical
      trial, and the cases were retrospectively collected and analyzed.

PMID- 27891177
TI  - Furfural tolerance and detoxification mechanism in Candida tropicalis.
AB  - BACKGROUND: Current biomass pretreatment by hydrothermal treatment (including
      acid hydrolysis, steam explosion, and high-temperature steaming) and ionic
      liquids generally generate inhibitors to the following fermentation process.
      Furfural is one of the typical inhibitors generated in hydrothermal treatment of
      biomass. Furfural could inhibit cell growth rate and decrease biofuel
      productivity of microbes. Candida tropicalis is a promising microbe for the
      production of biofuels and value-added chemicals using hemicellulose hydrolysate
      as carbon source. In this study, C. tropicalis showed a comparable ability of
      furfural tolerance during fermentation. We investigated the mechanism of C.
      tropicalis's robust tolerance to furfural and relevant metabolic responses to
      obtain more information for metabolic engineering of microbes for efficient
      lignocellulose fermentation. RESULTS: Candida tropicalis showed comparable
      intrinsic tolerance to furfural and a fast rate of furfural detoxification. C.
      tropicalis's half maximal inhibitory concentration for furfural with xylose as
      the sole carbon source was 3.69 g/L, which was higher than that of most wild-type
      microbes reported in the literature to our knowledge. Even though furfural
      prolonged the lag phase of C. tropicalis, the final biomass in the groups treated
      with 1 g/L furfural was slightly greater than that in the control groups. By real
      time PCR analysis, we found that the expression of ADH1 in C. tropicalis (ctADH1)
      was induced by furfural and repressed by ethanol after furfural depletion. The
      expression of ctADH1 could be regulated by both furfural and ethanol. After the
      disruption of gene ctADH1, we found that C. tropicalis's furfural tolerance was
      weakened. To further confirm the function of ctADH1 and enhance Escherichia
      coli's furfural tolerance, ctADH1 was overexpressed in E. coli BL21 (DE3). The
      rate of furfural degradation in E. coli BL21 (DE3) with pET-ADH1 (high-copy
      plasmid) and pCS-ADH1 (medium-copy plasmid) was increased by 1.59-fold and 1.28
      fold, respectively. CONCLUSIONS: Candida tropicalis was a robust strain with
      intrinsic tolerance to inhibitor furfural. The mechanism of furfural
      detoxification and metabolic responses were identified by multiple analyses.
      Alcohol dehydrogenase 1 was confirmed to be responsible for furfural
      detoxification. C. tropicalis showed a complex regulation system during furfural
      detoxification to minimize adverse effects caused by furfural. Furthermore, the
      mechanism we uncovered in this work was successfully applied to enhance E. coli's
      furfural tolerance by heterologous expression of ctADH1. The study provides
      deeper insights into strain modification for biofuel production by efficient
      lignocellulose fermentation.

PMID- 27891179
TI  - Compensation of feature selection biases accompanied with improved predictive
      performance for binary classification by using a novel ensemble feature selection
      approach.
AB  - MOTIVATION: Biomarker discovery methods are essential to identify a minimal
      subset of features (e.g., serum markers in predictive medicine) that are relevant
      to develop prediction models with high accuracy. By now, there exist diverse
      feature selection methods, which either are embedded, combined, or independent of
      predictive learning algorithms. Many preceding studies showed the defectiveness
      of single feature selection results, which cause difficulties for professionals
      in a variety of fields (e.g., medical practitioners) to analyze and interpret the
      obtained feature subsets. Whereas each of these methods is highly biased, an
      ensemble feature selection has the advantage to alleviate and compensate for such
      biases. Concerning the reliability, validity, and reproducibility of these
      methods, we examined eight different feature selection methods for binary
      classification datasets and developed an ensemble feature selection system.
      RESULTS: By using an ensemble of feature selection methods, a quantification of
      the importance of the features could be obtained. The prediction models that have
      been trained on the selected features showed improved prediction performance.

PMID- 27891181
TI  - Whole-genome sequencing and comparative genomic analysis of Escherichia coli O91
      strains isolated from symptomatic and asymptomatic human carriers.
AB  - BACKGROUND: The Shiga toxin-producing Escherichia coli (STEC) O91:H21 strains
      NCCP15736 and NCCP15737 were isolated during a single outbreak in Korea,
      NCCP15736 from a symptomatic carrier and NCCP15737 from an asymptomatic carrier.
      To investigate genomic differences between the two strains, we performed whole
      genome sequencing of both strains and conducted a comparative genomic analysis.
      RESULTS: Using the Illumina HiSeq 2000 platform and Rapid Annotation using the
      Subsystem Technology (RAST) server, whole-genome sequences of NCCP15736 and
      NCCP15737 were obtained and annotated. Phylogenetic analysis of ten E. coli
      strains showed that NCCP15736 and NCCP15737 are evolutionarily close. The two
      strains were found to be most close to E. coli O91:NM str. 2009C-3745. The
      genomic comparison showed that the fimD gene of NCCP15737 is truncated and that
      the truncation could underlie the defects in infection and pathogenicity of
      NCCP15737. The two strains showed the same virulence factor profiles, and we
      identified 25 virulence factors from NCCP15736 and NCCP15737, respectively. We
      identified ten and nine phage-associated regions in the NCCP15736 and NCCP15737
      genomes, respectively; the two strains share five of these. CONCLUSIONS:
      NCCP15736 and NCCP15737 differ at the genomic level, even though they share
      features such as virulence-related genes. NCCP15737 has a deletion in fimD, which
      may underlie its asymptomatic character. We conclude that complete genome
      sequencing and integration of other types of omics data are needed to fully
      reveal the mechanism underlying the asymptomatic character of NCCP15737.

PMID- 27891180
TI  - The effect of foot orthoses with forefoot cushioning or metatarsal pad on
      forefoot peak plantar pressure in running.
AB  - BACKGROUND: Foot orthoses are frequently used in sports for the treatment of
      overuse complaints with sufficient evidence available for certain foot-related
      overuse pathologies like plantar fasciitis, rheumatoid arthritis and foot pain
      (e.g., metatarsalgia). One important aim is to reduce plantar pressure under
      prominent areas like metatarsal heads. For the forefoot region, mainly two common
      strategies exist: metatarsal pad (MP) and forefoot cushioning (FC). The aim of
      this study was to evaluate which of these orthosis concepts is superior in
      reducing plantar pressure in the forefoot during running. METHODS: Twenty-three
      (13 female, 10 male) asymptomatic runners participated in this cross-sectional
      experimental trial. Participants ran in a randomised order under the two
      experimental (MP, FC) conditions and a control (C) condition on a treadmill (2.78
      ms-1) for 2 min, respectively. Plantar pressure was measured with the in-shoe
      plantar pressure measurement device pedar-x(r)-System and mean peak pressure
      averaged from ten steps in the forefoot (primary outcome) and total foot was
      analysed. Insole comfort was measured with the Insole Comfort Index (ICI, sum
      score 0-100) after each running trial. The primary outcome was tested using the
      Friedman test (alpha = 0.05). Secondary outcomes were analysed descriptively
      (mean +/- SD, lower & upper 95%-CI, median and interquartile-range (IQR)).
      RESULTS: Peak pressure [kPa] in the forefoot was significantly lower wearing FC
      (281 +/- 80, 95%-CI: 246-315) compared to both C (313 +/- 69, 95%-CI: 283-343; p
      = .003) and MP (315 +/- 80, 95%-CI: 280-350; p = .001). No significant difference
      was found between C and MP (p = .858). Peak pressures under the total foot were:
      C: 364 +/- 82, 95%-CI: 328-399; MP: 357 +/- 80, 95%-CI: 326-387; FC: 333 +/- 81
      95%-CI: 298-368. Median ICI sum scores were: C 50, MP 49, FC 64. CONCLUSIONS: In
      contrast to the metatarsal pad orthosis, the forefoot cushioning orthosis
      achieved a significant reduction of peak pressure in the forefoot of recreational
      runners. Consequently, the use of a prefabricated forefoot cushioning orthosis
      should be favoured over a prefabricated orthosis with an incorporated metatarsal
      pad in recreational runners with normal height arches.

PMID- 27891182
TI  - Case-control study of diarrheal disease etiology in individuals over 5 years in
      southwest China.
AB  - BACKGROUND: Acute diarrhea is one of the major public health problems worldwide.
      Most of studies on acute diarrhea have been made on infants aged below 5 years
      and few efforts have been made to identify the etiological agents of acute
      diarrhea in people over five, especially in China. METHODS: 271 diarrhea cases
      and 149 healthy controls over 5 years were recruited from four participating
      hospitals between June 2014 and July 2015. Each stool specimen was collected to
      detect a series of enteric pathogens, involving five viruses (Rotavirus group A,
      RVA; Norovirus, NoV; Sapovirus, SaV; Astrovirus, As; and Adenovirus, Ad), seven
      bacteria (diarrheagenic Escherichia coli, DEC; non-typhoidal Salmonella, NTS;
      Shigella spp.; Vibrio cholera; Vibrio parahaemolyticus; Aeromonas spp.; and
      Plesiomonas spp.) and three protozoa (Cryptosporidium spp., Giardia lamblia, G.
      lamblia, and Blastocystis hominis, B. hominis). Standard microbiological and
      molecular methods were applied to detect these pathogens. Data was analyzed using
      Chi square, Fisher-exact tests and logistic regressions. RESULTS: The prevalence
      of at least one enteric pathogen was detected in 29.2% (79/271) acute diarrhea
      cases and in 12.1% (18/149) in healthy controls (p < 0.0001). Enteric viral
      infections (14.4%) were the most common in patients suffering from acute
      diarrhea, followed by bacteria (13.7%) and intestinal protozoa (4.8%). DEC
      (12.5%) was the most common causative agent in diarrhea cases, followed by NoV
      GII (10.0%), RVA (7.4%) and B. hominis (4.8%). The prevalence of co-infection was
      statistically higher (p = 0.0059) in the case group (7.7%) than in the healthy
      control (1.3%). RVA-NoV GII (3.0%) was the most common co-infection in
      symptomatic cases. CONCLUSIONS: DEC was the most predominant pathogen in diarrhea
      cases, but it was largely overlooked because the lack of laboratory capacities.
      Because of the high prevalence of co-infections, it is recommended the urgent
      development of alternative laboratory methods to assess polymicrobial infections.
      Such methodological improvements will result in a better prevention and treatment
      strategies to control diarrhea illness in China.

PMID- 27891183
TI  - Complete genome of Vibrio parahaemolyticus FORC014 isolated from the toothfish.
AB  - BACKGROUND: Foodborne illness can occur due to various pathogenic bacteria such
      as Staphylococcus aureus, Escherichia coli and Vibrio parahaemolyticus, and can
      cause severe gastroenteritis symptoms. In this study, we completed the genome
      sequence of a foodborne pathogen V. parahaemolyticus FORC_014, which was isolated
      from suspected contaminated toothfish from South Korea. Additionally, we extended
      our knowledge of genomic characteristics of the FORC_014 strain through
      comparative analysis using the complete sequences of other V. parahaemolyticus
      strains whose complete genomes have previously been reported. RESULTS: The
      complete genome sequence of V. parahaemolyticus FORC_014 was generated using the
      PacBio RS platform with single molecule, real-time (SMRT) sequencing. The
      FORC_014 strain consists of two circular chromosomes (3,241,330 bp for chromosome
      1 and 1,997,247 bp for chromosome 2), one plasmid (51,383 bp), and one putative
      phage sequence (96,896 bp). The genome contains a total of 4274 putative protein
      coding sequences, 126 tRNA genes and 34 rRNA genes. Furthermore, we found 33 type
      III secretion system 1 (T3SS1) related proteins and 15 type III secretion system
      2 (T3SS2) related proteins on chromosome 1. This is the first reported result of
      Type III secretion system 2 located on chromosome 1 of V. parahaemolyticus
      without thermostable direct hemolysin (tdh) and thermostable direct hemolysin
      related hemolysin (trh). CONCLUSIONS: Through investigation of the complete
      genome sequence of V. parahaemolyticus FORC_014, which differs from previously
      reported strains, we revealed two type III secretion systems (T3SS1, T3SS2)
      located on chromosome 1 which do not include tdh and trh genes. We also
      identified several virulence factors carried by our strain, including iron uptake
      system, hemolysin and secretion system. This result suggests that the FORC_014
      strain may be one pathogen responsible for foodborne illness outbreak. Our
      results provide significant genomic clues which will assist in future
      understanding of virulence at the genomic level and help distinguish between
      clinical and non-clinical isolates.

PMID- 27891184
TI  - Effect of antibiotic pre-treatment and pathogen challenge on the intestinal
      microbiota in mice.
AB  - BACKGROUND: More than 50 years after the discovery of antibiotics, bacterial
      infections have decreased substantially; however, antibiotics also may have
      negative effects such as increasing susceptibility to pathogens. An intact
      microbiome is an important line of defense against pathogens. We sought to
      determine the effect of orally administered antibiotics both on susceptibility to
      pathogens and on impact to the microbiome. We studied Campylobacter jejuni, one
      of the most common causes of human diarrhea, and Acinetobacter baumannii, which
      causes wound infections. We examined the effects of antibiotic treatment on the
      susceptibility of mice to those pathogens as well as their influence on the mouse
      gut microbiome. RESULTS: In C57/BL6 mice models, we explored the effects of
      pathogen challenge, and antibiotic treatment on the intestinal microbiota. Mice
      were treated with either ciprofloxacin, penicillin, or water (control) for a 5
      day period followed by a 5-day washout period prior to oral challenge with C.
      jejuni or A. baumannii to assess antibiotic effects on colonization
      susceptibility. Mice were successfully colonized with C. jejuni more than 118
      days, but only transiently with A. baumannii. These challenges did not lead to
      any major effects on the composition of the gut microbiota. Although antibiotic
      pre-treatment did not modify pathogen colonization, it affected richness and
      community structure of the gut microbiome. However, the antibiotic dysbiosis was
      significantly reduced by pathogen challenge. CONCLUSIONS: We conclude that
      despite gut microbiota disturbance, susceptibility to gut colonization by these
      pathogens was unchanged. The major gut microbiome disturbance produced by
      antibiotic treatment may be reduced by colonization with specific microbial taxa.

PMID- 27891185
TI  - Spermatozoal cell death-inducing DNA fragmentation factor-alpha-like effector A
      (CIDEA) gene expression and DNA fragmentation in infertile men with metabolic
      syndrome and normal seminogram.
AB  - BACKGROUND: This is the first study to investigate spermatozoal cell death
      inducing DNA fragmentation factor-alpha-like effector A (CIDEA) gene expression
      and DNA fragmentations in the spermatozoa of men diagnosed with metabolic
      syndrome (MS) who have normal seminograms with unexplained infertility, and to
      correlate these parameters with seminal glucose concentration. METHODS: This
      study included 120 participants: 75 male subjects with MS (38 fertile and 37
      infertile), and a control group of 45 fertile males without MS. HOMA-IR, semen
      analysis, and biochemical measurement of seminal plasma insulin and glucose
      levels were carried out. Spermatozoal insulin gene and CIDEA gene expressions
      were performed by the RT-PCR method. The percentage of spermatozoal DNA
      fragmentation was also estimated. RESULTS: The spermatozoal insulin and CIDEA
      gene expression, as well as the DNA fragmentation, were significantly higher in
      the infertile MS group than in the fertile MS group, and significantly higher in
      both the MS groups than in the control group. Seminal glucose concentration
      showed significant positive correlations with seminal insulin level, spermatozoa
      insulin, CIDEA gene expression, and DNA fragmentation. Moreover, there was a
      positive correlation between spermatozoa CIDEA gene expression and DNA
      fragmentation. CONCLUSIONS: It can be concluded that MS may affect male fertility
      at the molecular level, through its possible inducing effect of spermatozoa CIDEA
      and insulin gene expression, DNA fragmentation, and increased seminal glucose.

PMID- 27891186
TI  - Relationship between vitamin D status, glycemic control and cardiovascular risk
      factors in Brazilians with type 2 diabetes mellitus.
AB  - OBJECTIVES: Determine the prevalence and identify predictors of hypovitaminosis D
      in patients with type 2 diabetes mellitus (T2DM); 2) correlate vitamin D levels
      with variables indicative of glycemic control and cardiovascular risk. RESEARCH
      DESIGN AND METHODS: We conducted a cross-sectional study with consecutive
      patients treated at a University Hospital's Endocrinology outpatient clinic
      located at 12 degrees 58'S latitude, between October 2012 and November 2013.
      Hypovitaminosis D was defined as 25-hydroxyvitamin D < 30 ng/mL
      (chemiluminescence). RESULTS: We evaluated 108 patients with mean duration of
      T2DM of 14.34 +/- 8.05 years and HbA1c of 9.2 +/- 2.1%. Mean age was 58.29 +/-
      10.34 years. Most were women (72.2%), non-white (89.8%) and had hypertension
      (75.9%) and dyslipidemia (76.8%). Mean BMI was 28.01 +/- 4.64 kg/m2; 75.9% were
      overweight. The prevalence of hypovitaminosis D was 62%. In multiple logistic
      regression, independent predictors of hypovitaminosis D were female gender (OR
      3.10, p = 0.02), dyslipidemia (OR 6.50, p < 0.01) and obesity (OR 2.55, p =
      0.07). In multiple linear regression, only total cholesterol (beta = -0.36, p <
      0.01) and BMI (beta = -0.21, p = 0.04) remained associated with levels of 25
      hydroxyvitamin D. CONCLUSIONS: Using currently recommended cutoffs, the
      prevalence of hypovitaminosis D in Brazilians with T2DM was as high as that of
      non-tropical regions. Female gender, dyslipidemia and obesity were predictors of
      hypovitaminosis D. Low levels of 25-hydroxyvitamin D were correlated with high
      cholesterol and BMI values. Future studies are needed to evaluate whether vitamin
      D replacement would improve these parameters and reduce hard cardiovascular
      outcomes.

PMID- 27891187
TI  - Mass spectrometry of analytical derivatives. 2. "Ortho" and "Para" effects in
      electron ionization mass spectra of derivatives of hydroxy, mercapto and amino
      benzoic acids.
AB  - Derivatives requiring either anhydrous or aqueous reaction conditions were
      prepared for robust and reliable gas chromatography/mass spectrometry (GC/MS)
      characterization of hydroxyl, mercapto, and amino benzoic acids Methylation and
      trialkylsilytation are employed for blocking the acidic function. Alkyl,
      trimethylsilyl, acetyl, perfluoroacyl and alkoxycarbonyl derivatization groups
      are introduced to hydroxyl, mercapto and amino functions. The electron ionization
      induced fragmentation characteristics of corresponding derivatives are explained
      by comparing the MS1 spectra of unlabeled compounds to their 2H and 13C labeled
      analogs, and analysis of collision-induced dissociation data from MS2 spectra.
      Competing fragmentation alternatives are identified and specific decomposition
      processes are detailed that characterize (a) ortho isomers due to interaction or
      vicinal functional substituents and (b) para isomers prone to forming para
      quinoid type structures. Skeletal and hydrogen rearrangements typical for methyl
      benzoates and the blocking groups are considered when discussing diagnostically
      important ions. Characteristic ions produced as a result of rearrangements in
      ortho isomers are classified, and skeletal rearrangements required to produce
      para quinoid type ions specific for para isomers are noted. Key ions for
      structure elucidation and differentiation of isomers for derivatives of
      substituted benzoic acids by GC/MS are suggested.

PMID- 27891188
TI  - Associations between social cognition, skills, and function and subclinical
      negative and positive symptoms in 22q11.2 deletion syndrome.
AB  - BACKGROUND: Identification of the early signs of schizophrenia would be a major
      achievement for the early intervention and prevention strategies in psychiatry.
      Social impairments are defining features of schizophrenia. Impairments of
      individual layers of social competencies are frequently described in individuals
      with 22q11.2 deletion syndrome (22q11.2DS), who have high risk of schizophrenia.
      It is unclear whether and to what extent social impairments associate with
      subclinical negative and positive symptoms in 22q11.2DS, and which layer of
      social impairments are more correlated with schizophrenia-related symptoms. The
      aims of this study were to conduct a comprehensive investigation of social
      impairments at three different levels (function, skill, and cognition) and their
      interrelationship and to determine to what degree the social impairments
      correlate to subclinical levels of negative and positive symptoms, respectively,
      in a young cohort of 22q11.2DS not diagnosed with schizophrenia. METHODS: The
      level of social impairment was addressed using questionnaires and objective
      measures of social functioning (The Adaptive Behavior Assessment System), skills
      (Social Responsiveness Scale), and cognition (The Awareness of Social Inference
      Test and CANTAB Emotional Recognition Task), and the presence of subclinical
      symptoms of schizophrenia were evaluated using the Structured Interview for
      Prodromal Syndromes in a cross-sectional case-control study of 29 cases and 29
      controls, aged 12 to 25 years. Association between social impairment and negative
      and positive symptoms levels was examined in cases only. RESULTS: Subjects with
      22q11.2DS were highly impaired in social function, social skills, and social
      cognition (p <= 6.2 * 10-9) relative to control peers and presented with more
      negative (p = 5.8 * 10-11) and positive (p = 7.5 * 10-4) symptoms. In particular,
      social functional and skill levels were highly associated with notably
      subclinical negative symptoms levels. CONCLUSIONS: This study shows strong
      correlations between levels of social impairments and subclinical negative and
      positive symptoms. However, longitudinal studies are required to show if social
      impairments represent early disease manifestations. If parental or self-reporting
      suggests severe social impairment, it should advocate for clinical awareness not
      only to social deficits per se but also of potential subclinical psychosis
      symptoms.

PMID- 27891189
TI  - Variations in DNA methylation of interferon gamma and programmed death 1 in
      allograft rejection after kidney transplantation.
AB  - BACKGROUND: The role of DNA methylation in the regulation of the anti-donor
      directed immune response after organ transplantation is unknown. Here, we studied
      the methylation of two mediators of the immune response: the pro-inflammatory
      cytokine interferon gamma (IFNgamma) and the inhibitory receptor programmed death
      1 (PD1) in naive and memory CD8+ T cell subsets in kidney transplant recipients
      receiving immunosuppressive medication. Both recipients experiencing an episode
      of acute allograft rejection (rejectors) as well as recipients without rejection
      (non-rejectors) were included. RESULTS: CpGs in the promoter regions of both
      IFNgamma and PD1 were significantly (p < 0.001) higher methylated in the naive
      CD8+ T cells compared to the memory T cell subsets. The methylation status of
      both IFNgamma and PD1 inversely correlated with the percentage of IFNgamma or PD1
      producing cells. Before transplantation, the methylation status of both IFNgamma
      and PD1 was not significantly different from healthy donors. At 3 months after
      transplantation, irrespective of rejection and subsequent anti-rejection therapy,
      the IFNy methylation was significantly higher in the differentiated effector
      memory CD45RA+ (EMRA) CD8+ T cells (p = 0.01) whereas the PD1 methylation was
      significantly higher in all memory CD8+ T cell subsets (CD27+ memory; p = 0.02:
      CD27- memory; p = 0.02: EMRA; p = 0.002). Comparing the increase in methylation
      in the first 3 months after transplantation between rejectors and non-rejectors
      demonstrated a significantly more prominent increase in the PD1 methylation in
      the CD27- memory CD8+ T cells in rejectors (increase in rejectors 14%, increase
      in non-rejectors 1.9%, p = 0.04). The increase in DNA methylation in the other
      memory CD8+ T cells was not significantly different between rejectors and non
      rejectors. At 12 months after transplantation, the methylation of both IFNgamma
      and PD1 returned to baseline levels. CONCLUSIONS: The DNA methylation of both
      IFNgamma and PD1 increases the first 3 months after transplantation in memory
      CD8+ T cells in kidney transplant recipients. This increase was irrespective of a
      rejection episode indicating that general factors of the kidney transplantation
      procedure, including the use of immunosuppressive medication, contribute to these
      variations in DNA methylation.

PMID- 27891190
TI  - Cell-free DNA promoter hypermethylation in plasma as a diagnostic marker for
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Pancreatic cancer has a 5-year survival rate of only 5-7%.
      Difficulties in detecting pancreatic cancer at early stages results in the high
      mortality and substantiates the need for additional diagnostic tools. Surgery is
      the only curative treatment and unfortunately only possible in localized tumours.
      A diagnostic biomarker for pancreatic cancer will have a major impact on patient
      survival by facilitating early detection and the possibility for curative
      treatment. DNA promoter hypermethylation is a mechanism of early carcinogenesis,
      which can cause inactivation of tumour suppressor genes. The aim of this study
      was to examine promoter hypermethylation in a panel of selected genes from cell
      free DNA, as a diagnostic marker for pancreatic adenocarcinoma. METHODS: Patients
      with suspected or biopsy-verified pancreatic cancer were included prospectively
      and consecutively. Patients with chronic/acute pancreatitis were included as
      additional benign control groups. Based on an optimized accelerated bisulfite
      treatment protocol, methylation-specific PCR of a 28 gene panel was performed on
      plasma samples. A diagnostic prediction model was developed by multivariable
      logistic regression analysis using backward stepwise elimination. RESULTS:
      Patients with pancreatic adenocarcinoma (n = 95), chronic pancreatitis (n = 97)
      and acute pancreatitis (n = 59) and patients screened, but negative for
      pancreatic adenocarcinoma (n = 27), were included. The difference in mean number
      of methylated genes in the cancer group (8.41 (95% CI 7.62-9.20)) vs the total
      control group (4.74 (95% CI 4.40-5.08)) was highly significant (p < 0.001). A
      diagnostic prediction model (age >65, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC,
      SFRP1 and SFRP2) had an area under the curve of 0.86 (sensitivity 76%,
      specificity 83%). The model performance was independent of cancer stage.
      CONCLUSIONS: Cell-free DNA promoter hypermethylation has the potential to be a
      diagnostic marker for pancreatic adenocarcinoma and differentiate between
      malignant and benign pancreatic disease. This study brings us closer to a
      clinical useful diagnostic marker for pancreatic cancer, which is urgently
      needed. External validation is, however, required before the test can be applied
      in the clinic. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02079363.

PMID- 27891191
TI  - Birth weight-for-gestational age is associated with DNA methylation at birth and
      in childhood.
AB  - BACKGROUND: Both higher and lower fetal growth are associated with cardio
      metabolic health later in life, suggesting that prenatal developmental
      programming determines long-term cardiovascular disease risk. Epigenetic
      mechanisms, which orchestrate fetal growth and development, may offer insight on
      the early programming of health and disease. We investigated whether birth weight
      for-gestational is associated with DNA methylation at birth and mid-childhood,
      measured via the Infinium 450K array. METHODS/RESULTS: Participants were from
      Project Viva, a pre-birth cohort of pregnant women and their children in Eastern
      Massachusetts. After exclusion of participants with maternal type 1 or 2 diabetes
      and gestational age <34 weeks, we used DNA methylation assays from 476 venous
      umbilical cord blood samples and a subset of 235 who additionally had peripheral
      blood samples available in mid-childhood (age 7-10 years). Among 392,918 CpG
      sites analyzed, birth weight-for-gestational age z-score was associated with cord
      blood DNA methylation at 34 CpGs (false discovery rate P < 0.05), after adjusting
      for maternal age, race/ethnicity, education, smoking, parity, delivery mode, pre
      pregnancy BMI, gestational diabetes status, child sex, and estimated cord blood
      cell proportions based on a cord blood reference panel. Two of these CpGs were
      previously reported in epigenome-wide analyses of birth weight, and several other
      CpGs map to genes relevant to fetal growth and development. Namely, higher birth
      weight-for-gestational age was associated with higher methylation at four CpGs at
      the PBX1 locus (e.g., beta (95% CI) for lead signal at cg06750897 = 1.9 (1.2,
      2.6)), which encodes a transcription factor that regulates embryonic development.
      Birth weight-for-gestational age was also associated with mid-childhood blood DNA
      methylation at four of the 34 CpGs identified in cord blood analyses, including
      sites at the PBX1 locus described. CONCLUSIONS: We identified CpG sites where
      birth weight-for-gestational age was associated with DNA methylation at birth,
      and for a subset of these sites, birth weight-for-gestational age was also
      associated with DNA methylation at mid-childhood.

PMID- 27891194
TI  - Erratum to: Donor age and C1orf132/MIR29B2C determine age-related methylation
      signature of blood after allogeneic hematopoietic stem cell transplantation.
AB  - [This corrects the article DOI: 10.1186/s13148-016-0257-7.].

PMID- 27891192
TI  - The quest for an effective and safe personalized cell therapy using epigenetic
      tools.
AB  - In the presence of different environmental cues that are able to trigger specific
      responses, a given genotype has the ability to originate a variety of different
      phenotypes. This property is defined as plasticity and allows cell fate
      definition and tissue specialization. Fundamental epigenetic mechanisms drive
      these modifications in gene expression and include DNA methylation, histone
      modifications, chromatin remodeling, and microRNAs. Understanding these
      mechanisms can provide powerful tools to switch cell phenotype and implement cell
      therapy. Environmentally influenced epigenetic changes have also been associated
      to many diseases such as cancer and neurodegenerative disorders, with patients
      that do not respond, or only poorly respond, to conventional therapy. It is clear
      that disorders based on an individual's personal genomic/epigenomic profile can
      rarely be successfully treated with standard therapies due to genetic
      heterogeneity and epigenetic alterations and a personalized medicine approach is
      far more appropriate to manage these patients. We here discuss the recent
      advances in small molecule approaches for personalized medicine, drug targeting,
      and generation of new cells for medical application. We also provide prospective
      views of the possibility to directly convert one cell type into another, in a
      safe and robust way, for cell-based clinical trials and regenerative medicine.

PMID- 27891193
TI  - In epithelial cancers, aberrant COL17A1 promoter methylation predicts its
      misexpression and increased invasion.
AB  - BACKGROUND: Metastasis is a leading cause of death among cancer patients. In the
      tumor microenvironment, altered levels of extracellular matrix proteins, such as
      collagens, can facilitate the first steps of cancer cell metastasis, including
      invasion into surrounding tissue and intravasation into the blood stream.
      However, the degree of misexpression of collagen genes in tumors remains
      understudied, even though this knowledge could greatly facilitate the development
      of cancer treatment options aimed at preventing metastasis. METHODS: We
      systematically evaluate the expression of all 44 collagen genes in breast cancer
      and assess whether their misexpression provides clinical prognostic significance.
      We use immunohistochemistry on 150 ductal breast cancers and 361 cervical cancers
      and study DNA methylation in various epithelial cancers. RESULTS: In breast
      cancer, various tests show that COL4A1 and COL4A2 overexpression and COL17A1
      (BP180, BPAG2) underexpression provide independent prognostic strength (HR =
      1.25, 95% CI = 1.17-1.34, p = 3.03 * 10-10; HR = 1.18, 95% CI = 1.11-1.25, p =
      8.11 * 10-10; HR = 0.86, 95% CI = 0.81-0.92, p = 4.57 * 10-6; respectively).
      Immunohistochemistry on ductal breast cancers confirmed that the COL17A1 protein
      product, collagen XVII, is underexpressed. This strongly correlates with advanced
      stage, increased invasion, and postmenopausal status. In contrast,
      immunohistochemistry on cervical tumors showed that collagen XVII is
      overexpressed in cervical cancer and this is associated with increased local
      dissemination. Interestingly, consistent with the opposed direction of
      misexpression in these cancers, the COL17A1 promoter is hypermethylated in breast
      cancer and hypomethylated in cervical cancer. We also find that the COL17A1
      promoter is hypomethylated in head and neck squamous cell carcinoma, lung
      squamous cell carcinoma, and lung adenocarcinoma, in all of which collagen XVII
      overexpression has previously been shown. CONCLUSIONS: Paradoxically, collagen
      XVII is underexpressed in breast cancer and overexpressed in cervical and other
      epithelial cancers. However, the COL17A1 promoter methylation status accurately
      predicts both the direction of misexpression and the increased invasive nature
      for five out of five epithelial cancers. This implies that aberrant epigenetic
      control is a key driver of COL17A1 gene misexpression and tumor cell invasion.
      These findings have significant clinical implications, suggesting that the
      COL17A1 promoter methylation status can be used to predict patient outcome.
      Moreover, epigenetic targeting of COL17A1 could represent a novel strategy to
      prevent metastasis in patients.

PMID- 27891195
TI  - Reflections on a giant of brain science: How lucky we are having Walter J.
      Freeman as our beacon in cognitive neurodynamics research.
AB  - Walter J. Freeman was a giant of the field of neuroscience whose visionary work
      contributed various experimental and theoretical breakthroughs to brain research
      in the past 60 years. He has pioneered a number of Electroencephalogram and
      Electrocorticogram tools and approaches that shaped the field, while "Freeman
      Neurodynamics" is a theoretical concept that is widely known, used, and respected
      among neuroscientists all over the world. His recent death is a profound loss to
      neuroscience and biomedical engineering. Many of his revolutionary ideas on brain
      dynamics have been ahead of their time by decades. We summarize his following
      groundbreaking achievements: (1) Mass Action in the Nervous System, from
      microscopic (single cell) recordings, through mesoscopic populations, to large
      scale collective brain patterns underlying cognition; (2) Freeman-Kachalsky model
      of multi-scale, modular brain dynamics; (3) cinematic theory of cognitive
      dynamics; (4) phase transitions in cortical dynamics modeled with random graphs
      and quantum field theory; (5) philosophical aspects of intentionality,
      consciousness, and the unity of brain-mind-body. His work has been admired by
      many of his neuroscientist colleagues and followers. At the same time, his
      multidisciplinary approach combining advanced concepts of control theory and the
      mathematics of nonlinear systems and chaos, poses significant challenges to those
      who wish to thoroughly understand his message. The goal of this commemorative
      paper is to review key aspects of Freeman's neurodynamics and to provide some
      handles to gain better understanding about Freeman's extraordinary intellectual
      achievement.

PMID- 27891196
TI  - Navigating abstract virtual environment: an eeg study.
AB  - Perceptions of different environments are different for different people. An
      abstract designed environment, with a degree of freedom from any visual reference
      in the physical world requests a completely different perception than a fully or
      semi-designed environment that has some correlation with the physical world.
      Maximal evidence on the manner in which the human brain is involved/operates in
      dealing with such novel perception comes from neuropsychology. Harnessing the
      tools and techniques involved in the domain of neuropsychology, the paper
      presents nee evidence on the role of pre-central gyrus in the perception of
      abstract spatial environments. In order to do so, the research team developed
      three different categories of designed environment with different
      characteristics: (1) Abstract environment, (2) Semi-designed environment, (3)
      Fully designed environment, as experimental sample environments. Perception of
      Fully-designed and semi-designed environments is almost the same, [maybe] since
      the brain can find a correlation between designed environments and already
      experienced physical world. In addition to this, the response to questionnaires
      accompanied with a list of buzzwords that have been provided after the
      experiments, also describe the characteristics of the chosen sample environments.
      Additionally, these results confirm the suitability of continuous
      electroencephalography (EEG) for studying Perception from the perspective of
      architectural environments.

PMID- 27891198
TI  - A novel method for early diagnosis of Alzheimer's disease based on higher-order
      spectral estimation of spontaneous speech signals.
AB  - One main challenge for medical investigators is the early diagnosis of
      Alzheimer's disease (AD) because it provides greater opportunities for patients
      to be eligible for more clinical trials. In this study, higher order spectra of
      human speech signals during AD were explored to analyze and compare the quadratic
      phase coupling of spontaneous speech signals for healthy and AD subjects using
      bispectrum and bicoherence. The results showed that the quadratic phase couplings
      of spontaneous speech signal of persons with Alzheimer's were reduced compared to
      healthy subject. However, the speech phase coupled harmonics shifted to the
      higher frequencies in Alzheimer's than healthy subjects. In addition, it was
      shown not only are there significant differences between Alzheimer's and control
      subjects in parameters estimated, but also the speech patterns appeared to have
      fluctuated in both types of spontaneous speech.

PMID- 27891199
TI  - Robust frequency recognition for SSVEP-based BCI with temporally local
      multivariate synchronization index.
AB  - Multivariate synchronization index (MSI) has been proved to be an efficient
      method for frequency recognition in SSVEP-BCI systems. It measures the
      correlation according to the entropy of the normalized eigenvalues of the
      covariance matrix of multichannel signals. In the MSI method, the estimation of
      covariance matrix omits the temporally local structure of samples. In this study,
      a new spatio-temporal method, termed temporally local MSI (TMSI), was presented.
      This new method explicitly exploits temporally local information in modelling the
      covariance matrix. In order to evaluate the performance of the TMSI, we performs
      a comparison between the two methods on the real SSVEP datasets from eleven
      subjects. The results show that the TMSI outperforms the standard MSI. TMSI
      benefits from exploiting the temporally local structure of EEG signals, and could
      be a potential method for robust performance of SSVEP-based BCI.

PMID- 27891197
TI  - The oscillation-like activity in bullfrog ON-OFF retinal ganglion cell.
AB  - Oscillatory activity of retinal ganglion cell (RGC) has been observed in various
      species. It was reported such oscillatory activity is raised within large neural
      network and involved in retinal information coding. In the present research, we
      found an oscillation-like activity in ON-OFF RGC of bullfrog retina, and studied
      the mechanisms underlying the ON and OFF activities respectively. Pharmacological
      experiments revealed that the oscillation-like activity patterns in both ON and
      OFF pathways were abolished by GABA receptor antagonists, indicating GABAergic
      inhibition is essential for generating them. At the meantime, such activities in
      the ON and OFF pathways showed different responses to several other applied
      drugs. The oscillation-like pattern in the OFF pathway was abolished by glycine
      receptor antagonist or gap junction blocker, whereas that in the ON pathway was
      not affected. Furthermore, the blockade of the ON pathway by metabotropic
      glutamate receptor agonist led to suppression of the oscillation-like pattern in
      the OFF pathway. These results suggest that the ON pathway has modulatory effect
      on the oscillation-like activity in the OFF pathway. Therefore, the mechanisms
      underlying the oscillation-like activities in the ON and OFF pathways are
      different: the oscillation-like activity in the ON pathway is likely caused by
      GABAergic amacrine cell network, while that in the OFF pathway needs the
      contributions of GABAergic and glycinergic amacrine cell network, as well as gap
      junction connections.

PMID- 27891202
TI  - New delay-interval-dependent stability criteria for switched Hopfield neural
      networks of neutral type with successive time-varying delay components.
AB  - This paper deals with the problem of delay-interval-dependent stability criteria
      for switched Hopfield neural networks of neutral type with successive time
      varying delay components. A novel Lyapunov-Krasovskii (L-K) functionals with
      triple integral terms which involves more information on the state vectors of the
      neural networks and upper bound of the successive time-varying delays is
      constructed. By using the famous Jensen's inequality, Wirtinger double integral
      inequality, introducing of some zero equations and using the reciprocal convex
      combination technique and Finsler's lemma, a novel delay-interval dependent
      stability criterion is derived in terms of linear matrix inequalities, which can
      be efficiently solved via standard numerical software. Moreover, it is also
      assumed that the lower bound of the successive leakage and discrete time-varying
      delays is not restricted to be zero. In addition, the obtained condition shows
      potential advantages over the existing ones since no useful term is ignored
      throughout the estimate of upper bound of the derivative of L-K functional. Using
      several examples, it is shown that the proposed stabilization theorem is
      asymptotically stable. Finally, illustrative examples are presented to
      demonstrate the effectiveness and usefulness of the proposed approach with a four
      tank benchmark real-world problem.

PMID- 27891201
TI  - The N170 component is sensitive to face-like stimuli: a study of Chinese Peking
      opera makeup.
AB  - The N170 component is considered a neural marker of face-sensitive processing. In
      the present study, the face-sensitive N170 component of event-related potentials
      (ERPs) was investigated with a modified oddball paradigm using a natural face
      (the standard stimulus), human- and animal-like makeup stimuli, scrambled control
      images that mixed human- and animal-like makeup pieces, and a grey control image.
      Nineteen participants were instructed to respond within 1000 ms by pressing the
      'F' or 'J' key in response to the standard or deviant stimuli, respectively. We
      simultaneously recorded ERPs, response accuracy, and reaction times. The
      behavioral results showed that the main effect of stimulus type was significant
      for reaction time, whereas there were no significant differences in response
      accuracies among stimulus types. In relation to the ERPs, N170 amplitudes
      elicited by human-like makeup stimuli, animal-like makeup stimuli, scrambled
      control images, and a grey control image progressively decreased. A right
      hemisphere advantage was observed in the N170 amplitudes for human-like makeup
      stimuli, animal-like makeup stimuli, and scrambled control images but not for
      grey control image. These results indicate that the N170 component is sensitive
      to face-like stimuli and reflect configural processing in face recognition.

PMID- 27891200
TI  - Semantic integration by pattern priming: experiment and cortical network model.
AB  - Neural network models describe semantic priming effects by way of mechanisms of
      activation of neurons coding for words that rely strongly on synaptic efficacies
      between pairs of neurons. Biologically inspired Hebbian learning defines efficacy
      values as a function of the activity of pre- and post-synaptic neurons only. It
      generates only pair associations between words in the semantic network. However,
      the statistical analysis of large text databases points to the frequent
      occurrence not only of pairs of words (e.g., "the way") but also of patterns of
      more than two words (e.g., "by the way"). The learning of these frequent patterns
      of words is not reducible to associations between pairs of words but must take
      into account the higher level of coding of three-word patterns. The processing
      and learning of pattern of words challenges classical Hebbian learning algorithms
      used in biologically inspired models of priming. The aim of the present study was
      to test the effects of patterns on the semantic processing of words and to
      investigate how an inter-synaptic learning algorithm succeeds at reproducing the
      experimental data. The experiment manipulates the frequency of occurrence of
      patterns of three words in a multiple-paradigm protocol. Results show for the
      first time that target words benefit more priming when embedded in a pattern with
      the two primes than when only associated with each prime in pairs. A biologically
      inspired inter-synaptic learning algorithm is tested that potentiates synapses as
      a function of the activation of more than two pre- and post-synaptic neurons.
      Simulations show that the network can learn patterns of three words to reproduce
      the experimental results.

PMID- 27891203
TI  - Effect of different glucose supply conditions on neuronal energy metabolism.
AB  - The glucose-excited neurons in brain can sense blood glucose levels and reflect
      different firing states, which are mainly associated with regulation of blood
      glucose and energy demand in the brain. In this paper, a new model of glucose
      excited neuron in hypothalamus is proposed. The firing properties and energy
      consumption of this type of neuron under conditions of different glucose levels
      are simulated and analyzed. The results show that the firing rate and firing
      duration of the neuron both increase with increasing extracellular glucose
      levels, but the maximum energy power for an AP is reduced. Further study suggests
      that the neuron firstly absorbs energy substrates (e.g. glucose) from the blood
      to prepare for the high energy demand of high-frequency spikes.

PMID- 27891204
TI  - Neutral impulsive shunting inhibitory cellular neural networks with time-varying
      coefficients and leakage delays.
AB  - In this article, we consider a class of neutral impulsive shunting inhibitory
      cellular neural networks with time varying coefficients and leakage delays. We
      study the existence and the exponential stability of the piecewise differentiable
      pseudo almost-periodic solutions and establish sufficient conditions for the
      existence and exponential stability of such solutions. An example is provided to
      illustrate the theory developed in this work.

PMID- 27891205
TI  - The membrane potential process of a single neuron seen as a cumulative damage
      process.
AB  - A simple integrate-and-fire mechanism of a single neuron can be compared with a
      cumulative damage process, where the spiking process is analogous to rupture
      sequences of a material under cycles of stress. Although in some cases lognormal
      like patterns can be recognized in the inter-spike times under a simple integrate
      and-fire mechanism, fatigue life models as the inverse Gaussian distribution and
      the Birnbaum-Saunders distribution (which was recently introduced in the neural
      activity framework) provide theoretical arguments that make them more suitable
      for the modeling of the resulting inter-spike times.

PMID- 27891206
TI  - Atomic Structural Evolution during the Reduction of alpha-Fe2O3 Nanowires.
AB  - The atomic-scale reduction mechanism of alpha-Fe2O3 nanowires by H2 was followed
      using transmission electron microscopy to reveal the evolution of atomic
      structures and the associated transformation pathways for different iron oxides.
      The reduction commences with the generation of oxygen vacancies that order onto
      every 10th [Formula: see text] plane. This vacancy ordering is followed by an
      allotropic transformation of alpha-Fe2O3 -> gamma-Fe2O3 along with the formation
      of Fe3O4 nanoparticles on the surface of the gamma-Fe2O3 nanowire by a topotactic
      transformation process, which shows 3D correspondence between the structures of
      the product and its host. These observations demonstrate that the partial
      reduction of alpha-Fe2O3 nanowires results in the formation of a unique
      hierarchical structure of hybrid oxides consisting of the parent oxide phase,
      gamma-Fe2O3, as the one-dimensional wire and the Fe3O4 in the form of
      nanoparticles decorated on the parent oxide skeleton. We show that the proposed
      mechanism is consistent with previously published and our density functional
      theory results on the thermodynamics of surface termination and oxygen vacancy
      formation in alpha-Fe2O3. Compared to previous reports of alpha-Fe2O3 directly
      transformed to Fe3O4, our work provides a more in-depth understanding with
      substeps of reduction, i.e., the whole reduction process follows: alpha-Fe2O3 ->
      alpha-Fe2O3 superlattice -> gamma-Fe2O3 + Fe3O4-> Fe3O4.

PMID- 27891207
TI  - The Antiapoptosis Effect of Glycyrrhizate on HepG2 Cells Induced by Hydrogen
      Peroxide.
AB  - This study demonstrated that glycyrrhizate (GAS) could protect HEPG2 cells
      against damage and apoptosis induced by H2O2 (1600 MUM, 4 h). Cell viability
      assay revealed that GAS was noncytotoxity at concentration 125 ug/mL, and GAS (5
      MUg/mL, 25 MUg/mL, and 125 MUg/mL) protected HepG2 cells against H2O2-induced
      cytotoxicity. H2O2 induced the HepG2 cells apoptosis, obvious morphologic changes
      were observed after Hochest 33258 staining, and more apoptotic cells were counted
      in flow cytometry assay compared to that of the natural group. Pretreatment GAS
      (5 MUg/mL, 25 MUg/mL, and 125 MUg/mL) prior to H2O2 reverses the morphologic
      changes and reduced the apoptotic cells in HepG2 cells. GAS reduced the release
      of MDA, increased the activities of superoxide dismutase, and diminished the
      release of ALT and AST during oxidative stress in HepG2 cells. After Elisa kit
      detecting, GAS inhibited the caspase activity induced by H2O2, GAS decreased the
      level of caspase-3 and caspase-9 from mitochondria in dose-dependent manner.
      Western blot results showed that pretreatment GAS upregulated the expression of
      Bcl-2 and decreased the expression of Bax. These results reveal that GAS has the
      cytoprotection in HepG2 cells during ROS exposure by inhibiting the caspase
      activity in the mitochondria and influencing apoptogenic factors of the
      expression of Bax and Bcl-2.

PMID- 27891208
TI  - Endogenous n-3 Fatty Acids Alleviate Carbon-Tetrachloride-Induced Acute Liver
      Injury in Fat-1 Transgenic Mice.
AB  - n-3 polyunsaturated fatty acids (PUFAs) are beneficial for numerous models of
      liver diseases. The probable protective effects of n-3 PUFA against carbon
      tetrachloride- (CCl4-) induced acute liver injury were evaluated in a fat-1
      transgenic mouse that synthesizes endogenous n-3 from n-6 PUFA. Fat-1 mice and
      their WT littermates were fed a modified AIN93 diet containing 10% corn oil and
      were injected intraperitoneally with a single dose of CCl4 or vehicle. CCl4
      challenge caused severe liver injury in WT mice, as indicated by serum parameters
      and histopathological changes, which were remarkably ameliorated in fat-1 mice.
      Endogenous n-3 PUFA decreased the elevation of oxidative stress induced by CCl4
      challenge, which might be attributed to the activation of Nrf2/keap1 pathway.
      Additionally, endogenous n-3 PUFA reduces hepatocyte apoptosis via suppressing
      MAPK pathway. These findings indicate that n-3 PUFA has potent protective effects
      against acute liver injury induced by CCl4 in mice, suggesting that n-3 PUFA can
      be used for the prevention and treatment of liver injury.

PMID- 27891209
TI  - Feasibility of Connecting, a Substance-Abuse Prevention Program for Foster Teens
      and their Caregivers.
AB  - OBJECTIVE: To test the feasibility, usability, and proximal outcomes of
      Connecting, an adaptation of a low-cost, self-directed, family-based substance
      use prevention program, Staying Connected with Your Teen, with foster families in
      a randomized, waitlist control pilot study. METHOD: Families (n = 60) fostering
      teens between 11 and 15 years of age were recruited into the study and randomly
      assigned into the self-administered program with telephone support from a family
      consultant (n = 32) or a waitlist control condition (n = 28). RESULTS: Overall
      satisfaction with the program was high, with 100% of parents reporting they would
      recommend the program to other caregivers and reporting being "very satisfied" or
      "satisfied with the program. Program completion was good, with 62% of families
      completing all 91 specified tasks. Analyses of proximal outcomes revealed
      increased communication about sex and substance use (posttest1 OR = 1.97, and
      2.03, respectively). Teens in the intervention vs. the waitlist condition
      reported lower family conflict (OR=.48), and more family rules related to
      monitoring (OR = 4.02) and media use (OR = 3.24). Caregivers in the waitlist
      group reported significant increases in the teen's positive involvements (partial
      eta sq = 17% increase) after receiving the intervention. CONCLUSIONS: Overall,
      program participation appeared to lead to stronger family management, better
      communication between teens and caregivers around monitoring and media use, teen
      participation in setting family rules, and decreased teen attitudes favorable to
      antisocial behavior. This small pilot study shows promising results for this
      adapted program.

PMID- 27891210
TI  - Software-defined Radio Based Measurement Platform for Wireless Networks.
AB  - End-to-end latency is critical to many distributed applications and services that
      are based on computer networks. There has been a dramatic push to adopt wireless
      networking technologies and protocols (such as WiFi, ZigBee, WirelessHART,
      Bluetooth, ISA100.11a, etc.) into time-critical applications. Examples of such
      applications include industrial automation, telecommunications, power utility,
      and financial services. While performance measurement of wired networks has been
      extensively studied, measuring and quantifying the performance of wireless
      networks face new challenges and demand different approaches and techniques. In
      this paper, we describe the design of a measurement platform based on the
      technologies of software-defined radio (SDR) and IEEE 1588 Precision Time
      Protocol (PTP) for evaluating the performance of wireless networks.

PMID- 27891211
TI  - From linked open data to molecular interaction: studying selectivity trends for
      ligands of the human serotonin and dopamine transporter.
AB  - Retrieval of congeneric and consistent SAR data sets for protein targets of
      interest is still a laborious task to do if no appropriate in-house data set is
      available. However, combining integrated open data sources (such as the Open
      PHACTS Discovery Platform) with workflow tools now offers the possibility of
      querying across multiple domains and tailoring the search to the given research
      question. Starting from two phylogenetically related protein targets of interest
      (the human serotonin and dopamine transporters), the whole chemical compound
      space was explored by implementing a scaffold-based clustering of compounds
      possessing biological measurements for both targets. In addition, potential hERG
      blocking liabilities were included. The workflow allowed studying the selectivity
      trends of scaffold series, identifying potentially harmful compound series, and
      performing SAR, docking studies and molecular dynamics (MD) simulations for a
      consistent data set of 56 cathinones. This delivered useful insights into driving
      determinants for hDAT selectivity over hSERT. With respect to the scaffold-based
      analyses it should be noted that the cathinone data set could be retrieved only
      when Murcko scaffold analyses were combined with similarity searches such as a
      common substructure search.

PMID- 27891212
TI  - The role of sex-differential biology in risk for autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a developmental condition that affects
      approximately four times as many males as females, a strong sex bias that has not
      yet been fully explained. Understanding the causes of this biased prevalence may
      highlight novel avenues for treatment development that could benefit patients
      with diverse genetic backgrounds, and the expertise of sex differences
      researchers will be invaluable in this endeavor. In this review, I aim to assess
      current evidence pertaining to the sex difference in ASD prevalence and to
      identify outstanding questions and remaining gaps in our understanding of how
      males come to be more frequently affected and/or diagnosed with ASD. Though males
      consistently outnumber females in ASD prevalence studies, prevalence estimates
      generated using different approaches report male/female ratios of variable
      magnitude that suggest that ascertainment or diagnostic biases may contribute to
      the male skew in ASD. Here, I present the different methods applied and
      implications of their findings. Additionally, even as prevalence estimations
      challenge the degree of male bias in ASD, support is growing for the long
      proposed female protective effect model of ASD risk, and I review the relevant
      results from recurrence rate, quantitative trait, and genetic analyses. Lastly, I
      describe work investigating several sex-differential biological factors and
      pathways that may be responsible for females' protection and/or males' increased
      risk predicted by the female protective effect model, including sex steroid
      hormone exposure and regulation and sex-differential activity of certain neural
      cell types. However, much future work from both the ASD and sex differences
      research communities will be required to flesh out our understanding of how these
      factors act to influence the developing brain and modulate ASD risk.

PMID- 27891214
TI  - One-step immortalization of primary human airway epithelial cells capable of
      oncogenic transformation.
AB  - BACKGROUND: The ability to transform normal human cells into cancer cells with
      the introduction of defined genetic alterations is a valuable method for
      understanding the mechanisms of oncogenesis. Easy establishment of immortalized
      but non-transformed human cells from various tissues would facilitate these
      genetic analyses. RESULTS: We report here a simple, one-step immortalization
      method that involves retroviral vector mediated co-expression of the human
      telomerase protein and a shRNA targeting the CDKN2A gene locus. We demonstrate
      that this method could successfully immortalize human small airway epithelial
      cells while maintaining their chromosomal stability. We further showed that these
      cells retain p53 activity and can be transformed by the KRAS oncogene.
      CONCLUSIONS: Our method simplifies the immortalization process and is broadly
      applicable for establishing immortalized epithelial cell lines from primary human
      tissues for cancer research.

PMID- 27891215
TI  - Hypothesis: may e-cigarette smoking boost the allergic epidemic?

PMID- 27891213
TI  - UK guidelines for the management of soft tissue sarcomas.
AB  - Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues, and
      can occur almost anywhere in the body. Their rarity, and the heterogeneity of
      subtype and location means that developing evidence-based guidelines is
      complicated by the limitations of the data available. However, this makes it more
      important that STS are managed by teams, expert in such cases, to ensure
      consistent and optimal treatment, as well as recruitment to clinical trials, and
      the ongoing accumulation of further data and knowledge. The development of
      appropriate guidance, by an experienced panel referring to the evidence
      available, is therefore a useful foundation on which to build progress in the
      field. These guidelines are an update of the previous version published in 2010
      (Grimer et al. in Sarcoma 2010:506182, 2010). The original guidelines were drawn
      up following a consensus meeting of UK sarcoma specialists convened under the
      auspices of the British Sarcoma Group (BSG) and were intended to provide a
      framework for the multidisciplinary care of patients with soft tissue sarcomas.
      This current version has been updated and amended with reference to other
      European and US guidance. There are specific recommendations for the management
      of selected subtypes of disease including retroperitoneal and uterine sarcomas,
      as well as aggressive fibromatosis (desmoid tumours) and other borderline tumours
      commonly managed by sarcoma services. An important aim in sarcoma management is
      early diagnosis and prompt referral. In the UK, any patient with a suspected soft
      tissue sarcoma should be referred to one of the specialist regional soft tissues
      sarcoma services, to be managed by a specialist sarcoma multidisciplinary team.
      Once the diagnosis has been confirmed using appropriate imaging, plus a biopsy,
      the main modality of management is usually surgical excision performed by a
      specialist surgeon. In tumours at higher risk of recurrence or metastasis pre- or
      post-operative radiotherapy should be considered. Systemic anti-cancer therapy
      (SACT) may be utilized in some cases where the histological subtype is considered
      more sensitive to systemic treatment. Regular follow-up is recommended to assess
      local control, development of metastatic disease, and any late-effects of
      treatment. For local recurrence, and more rarely in selected cases of metastatic
      disease, surgical resection would be considered. Treatment for metastases may
      include radiotherapy, or systemic therapy guided by the sarcoma subtype. In some
      cases, symptom control and palliative care support alone will be appropriate.

PMID- 27891216
TI  - Evolution of the elaborate male intromittent organ of Xiphophorus fishes.
AB  - Internally fertilizing animals show a remarkable diversity in male genital
      morphology that is associated with sexual selection, and these traits are thought
      to be evolving particularly rapidly. Male fish in some internally fertilizing
      species have "gonopodia," highly modified anal fins that are putatively important
      for sexual selection. However, our understanding of the evolution of genital
      diversity remains incomplete. Contrary to the prediction that male genital traits
      evolve more rapidly than other traits, here we show that gonopodial traits and
      other nongonopodial traits exhibit similar evolutionary rates of trait change and
      also follow similar evolutionary models in an iconic genus of poeciliid fish
      (Xiphophorus spp.). Furthermore, we find that both mating and nonmating natural
      selection mechanisms are unlikely to be driving the diverse Xiphophorus
      gonopodial morphology. Putative holdfast features of the male genital organ do
      not appear to be influenced by water flow, a candidate selective force in aquatic
      habitats. Additionally, interspecific divergence in gonopodial morphology is not
      significantly higher between sympatric species, than between allopatric species,
      suggesting that male genitals have not undergone reproductive character
      displacement. Slower rates of evolution in gonopodial traits compared with a
      subset of putatively sexually selected nongenital traits suggest that different
      selection mechanisms may be acting on the different trait types. Further
      investigations of this elaborate trait are imperative to determine whether it is
      ultimately an important driver of speciation.

PMID- 27891217
TI  - Models of Eucalypt phenology predict bat population flux.
AB  - Fruit bats (Pteropodidae) have received increased attention after the recent
      emergence of notable viral pathogens of bat origin. Their vagility hinders data
      collection on abundance and distribution, which constrains modeling efforts and
      our understanding of bat ecology, viral dynamics, and spillover. We addressed
      this knowledge gap with models and data on the occurrence and abundance of
      nectarivorous fruit bat populations at 3 day roosts in southeast Queensland. We
      used environmental drivers of nectar production as predictors and explored
      relationships between bat abundance and virus spillover. Specifically, we
      developed several novel modeling tools motivated by complexities of fruit bat
      foraging ecology, including: (1) a dataset of spatial variables comprising
      Eucalypt-focused vegetation indices, cumulative precipitation, and temperature
      anomaly; (2) an algorithm that associated bat population response with spatial
      covariates in a spatially and temporally relevant way given our current
      understanding of bat foraging behavior; and (3) a thorough statistical learning
      approach to finding optimal covariate combinations. We identified covariates that
      classify fruit bat occupancy at each of our three study roosts with 86-93%
      accuracy. Negative binomial models explained 43-53% of the variation in observed
      abundance across roosts. Our models suggest that spatiotemporal heterogeneity in
      Eucalypt-based food resources could drive at least 50% of bat population behavior
      at the landscape scale. We found that 13 spillover events were observed within
      the foraging range of our study roosts, and they occurred during times when
      models predicted low population abundance. Our results suggest that, in southeast
      Queensland, spillover may not be driven by large aggregations of fruit bats
      attracted by nectar-based resources, but rather by behavior of smaller resident
      subpopulations. Our models and data integrated remote sensing and statistical
      learning to make inferences on bat ecology and disease dynamics. This work
      provides a foundation for further studies on landscape-scale population movement
      and spatiotemporal disease dynamics.

PMID- 27891218
TI  - Projected changes in climatic suitability for Kinosternon turtles by 2050 and
      2070.
AB  - Chelonians are expected to be negatively impacted by climate change due to
      limited vagility and temperature-dependent sex determination. However, few
      studies have examined how freshwater turtle distributions may shift under
      different climate change scenarios. We used a maximum entropy approach to model
      the distribution of five widespread North American Kinosternon species (K.
      baurii, K. flavescens, K. hirtipes, K. sonoriense, and K. subrubrum) under four
      climate change scenarios. We found that areas with suitable climatic conditions
      for K. baurii and K. hirtipes are expected to decline substantially during the
      21st century. In contrast, the area with suitable climate for K. sonoriense will
      remain essentially unchanged, while areas suitable for K. flavescens and K.
      subrubrum are expected to substantially increase. The centroid for the
      distribution of four of the five species shifted northward, while the centroid
      for K. sonoriense shifted slightly southward. Overall, centroids shifted at a
      median rate of 37.5 km per decade across all scenarios. Given the limited
      dispersal ability of turtles, it appears unlikely that range shifts will occur
      rapidly enough to keep pace with climate change during the 21st century. The
      ability of chelonians to modify behavioral and physiological responses in
      response to unfavorable conditions may allow turtles to persist for a time in
      areas that have become increasingly unsuitable, but this plasticity will likely
      only delay local extinctions.

PMID- 27891219
TI  - Environmental selection is a main driver of divergence in house sparrows (Passer
      domesticus) in Romania and Bulgaria.
AB  - Both neutral and adaptive evolutionary processes can cause population divergence,
      but their relative contributions remain unclear. We investigated the roles of
      these processes in population divergence in house sparrows (Passer domesticus)
      from Romania and Bulgaria, regions characterized by high landscape heterogeneity
      compared to Western Europe. We asked whether morphological divergence,
      complemented with genetic data in this human commensal species, was best
      explained by environmental variation, geographic distance, or landscape
      resistance-the effort it takes for an individual to disperse from one location to
      the other-caused by either natural or anthropogenic barriers. Using generalized
      dissimilarity modeling, a matrix regression technique that fits biotic beta
      diversity to both environmental predictors and geographic distance, we found that
      a small set of climate and vegetation variables explained up to ~30% of the
      observed divergence, whereas geographic and resistance distances played much
      lesser roles. Our results are consistent with signals of selection on
      morphological traits and of isolation by adaptation in genetic markers,
      suggesting that selection by natural environmental conditions shapes population
      divergence in house sparrows. Our study thus contributes to a growing body of
      evidence that adaptive evolution may be a major driver of diversification.

PMID- 27891220
TI  - Diversification in wild populations of the model organism Anolis carolinensis: A
      genome-wide phylogeographic investigation.
AB  - The green anole (Anolis carolinensis) is a lizard widespread throughout the
      southeastern United States and is a model organism for the study of reproductive
      behavior, physiology, neural biology, and genomics. Previous phylogeographic
      studies of A. carolinensis using mitochondrial DNA and small numbers of nuclear
      loci identified conflicting and poorly supported relationships among
      geographically structured clades; these inconsistencies preclude confident use of
      A. carolinensis evolutionary history in association with morphological,
      physiological, or reproductive biology studies among sampling localities and
      necessitate increased effort to resolve evolutionary relationships among natural
      populations. Here, we used anchored hybrid enrichment of hundreds of genetic
      markers across the genome of A. carolinensis and identified five strongly
      supported phylogeographic groups. Using multiple analyses, we produced a fully
      resolved species tree, investigated relative support for each lineage across all
      gene trees, and identified mito-nuclear discordance when comparing our results to
      previous studies. We found fixed differences in only one clade-southern Florida
      restricted to the Everglades region-while most polymorphisms were shared between
      lineages. The southern Florida group likely diverged from other populations
      during the Pliocene, with all other diversification during the Pleistocene.
      Multiple lines of support, including phylogenetic relationships, a latitudinal
      gradient in genetic diversity, and relatively more stable long-term population
      sizes in southern phylogeographic groups, indicate that diversification in A.
      carolinensis occurred northward from southern Florida.

PMID- 27891221
TI  - Brood size moderates associations between relative size, telomere length, and
      immune development in European starling nestlings.
AB  - For young birds in a nest, body size may have implications for other aspects of
      development such as telomere length and immune function. However, it is possible
      to predict associations in either direction. On the one hand, there may be trade
      offs between growth and telomere maintenance, and growth and investment in immune
      function, suggesting there will be negative correlations. On the other hand,
      relatively larger individuals might be advantaged in competition with their nest
      mates, allowing them to garner more resources overall, leading to positive
      correlations. We studied development over the nestling period in 34 nests of wild
      European starlings, Sturnus vulgaris. Intrabrood competition is typically more
      intense in larger broods. Hence, we predicted that body size should become an
      increasingly positive predictor of telomere length and immune functioning as
      brood size increases. In partial support of our prediction, there were
      significant interactions between brood size and body size in predicting both
      erythrocyte telomere length change and plasma levels of the cytokine interleukin
      6. The associations between body size and these outcomes went from negative in
      the smallest broods to positive in the largest. A further immune marker, high
      sensitivity C-reactive protein, showed no systematic patterning with body size or
      brood size. Our results confirm that the size to which a nestling grows is
      important for telomere dynamics and the development of the immune system, but the
      phenotypic associations are moderated by the competitive context.

PMID- 27891222
TI  - Epidemiology of Klebsiella pneumoniae bloodstream infections in a teaching
      hospital: factors related to the carbapenem resistance and patient mortality.
AB  - BACKGROUND: Although Klebsiella pneumoniae bloodstream infections (KP-BSIs) have
      recently attracted attention due to an alarming raise in morbidity and mortality,
      there have been few reports on the epidemiology of KP-BSIs in mainland China. We
      sought to describe the epidemiological, microbiological, and clinical
      characteristics of KP-BSIs, focusing on the risk factors of carbapenem resistance
      and patient mortality. METHODS: A retrospective analysis of WHONET data of KP-BSI
      patients admitted to a teaching hospital in Shanghai, China, between January 1,
      2011 and December 31, 2015 was performed, and the annual percentage of patients
      with carbapenem-resistant K. pneumoniae (CRKP) was determined. Risk factors
      related to the carbapenem resistance and patient mortality were analyzed using
      binary logistic regression model. The genetic relatedness of CRKP strains
      isolated from intensive care unit (ICU) patients was determined by pulsed-field
      gel electrophoresis (PFGE). RESULTS: A total of 293 incidences of KP-BSIs were
      identified in a 5-year period, 22.18% of these (65/293) were CRKP strains, and
      the proportion of CRKP-BSI in ICU was 59.62% (31/52), equaling the levels
      observed in the epidemic regions. A number of KP-BSIs (114), obtained from
      January 1, 2014, to December 31, 2015, were further investigated. Skin and soft
      tissue infection source (odds ratio [OR] 26.63, 95% confidence interval [CI] 4.8
      146.8) and ICU-acquired infection (OR 5.82, 95% CI 2.0-17.2) was shown to be
      powerful risk factors leading to the development of CRKP-BSI. The crude 28-day
      mortality rates of KP-BSI and CRKP-BSI patients were 22.8% and 33.3%,
      respectively. Lung as the probable source of infection (OR 4.23, 95% CI 1.0
      17.3), and high Sequential Organ Failure Assessment (SOFA) score (OR 1.40, 95% CI
      1.2-1.6) were strong prognostic factors determining crude 28-day KP-BSI mortality
      rates. PFGE analysis demonstrated that 10/11 random CRKP isolates in ICU belonged
      to the same clonal type. CONCLUSIONS: During the study period, we observed a
      significant increase in the occurrence of CRKP infections among the identified KP
      BSIs in our hospital and especially in ICU, and we demonstrated that carbapenem
      resistance is associated with the increased mortality of KP-BSI patients.

PMID- 27891223
TI  - Is ApoE E 4 a good biomarker for amyloid pathology in late onset Alzheimer's
      disease?
AB  - Amyloid plaques are pathological hallmarks of Alzheimer's Disease (AD) and
      biomarkers such as cerebrospinal fluid (CSF) beta-amyloid 1-42 (Abeta1-42) and
      amyloid positron emission tomographic (PET) imaging are important in diagnosing
      amyloid pathology in vivo. E4 allele of the Apolipoprotein E gene (ApoE E 4),
      which is a major genetic risk factor for late onset AD, is an important genetic
      biomarker for AD pathophysiology. It has been shown that ApoE E 4 is involved in
      Abeta deposition and formation of amyloid plaques. Studies have suggested the
      utility of peripheral blood ApoE E 4 in AD diagnosis and risk assessment. However
      it is still a matter of debate whether ApoE E 4 status would improve prediction
      of amyloid pathology and represent a cost-effective alternative to amyloid PET or
      CSF Abeta in resource-limited settings in late onset AD. Recent research suggest
      that the mean prevalence of PET amyloid-positivity is 95% in ApoE E 4-positive AD
      patients. This short review aims to provide an updated information on the
      relationship between ApoE E 4 and amyloid biomarkers.

PMID- 27891224
TI  - TCR signaling by conventional CD4+ T cells is required for optimal maintenance of
      peripheral regulatory T cell numbers.
AB  - To maintain immune tolerance, regulatory T cell (Treg) numbers must be closely
      indexed to the number of conventional T cells (Tconvs) so that an adequate
      Treg:Tconv ratio can be maintained. Two factors important in this process are the
      cytokine interleukin-2 (IL-2) and T cell receptor (TCR) stimulation by major
      histocompatibility complex class II (MHC-II). Here, we report that in addition to
      TCR stimulation of Tregs themselves, the maintenance of Tregs also requires TCR
      signaling by Tconvs. We found that Tconvs produce IL-2 in response to self
      peptide-MHC-II complexes and that Tconvs possessing more highly self-reactive
      TCRs express more IL-2 at baseline. Furthermore, selective disruption of TCR
      signaling in Tconvs led to a trend toward decreased expression of IL-2 and
      attenuated their ability to maintain Treg numbers. These data suggest that in
      order to maintain an adequate Treg:Tconv ratio, Tregs are continuously indexed to
      self-peptide-MHC-II-induced TCR signaling of Tconvs. These results have
      implications in attempts to modulate immune tolerance, as Treg numbers adjust to
      the self-reactivity, and ultimately IL-2 production by the T cells around them.

PMID- 27891226
TI  - Validation of biomarkers to predict response to immunotherapy in cancer: Volume
      II - clinical validation and regulatory considerations.
AB  - There is growing recognition that immunotherapy is likely to significantly
      improve health outcomes for cancer patients in the coming years. Currently, while
      a subset of patients experience substantial clinical benefit in response to
      different immunotherapeutic approaches, the majority of patients do not but are
      still exposed to the significant drug toxicities. Therefore, a growing need for
      the development and clinical use of predictive biomarkers exists in the field of
      cancer immunotherapy. Predictive cancer biomarkers can be used to identify the
      patients who are or who are not likely to derive benefit from specific
      therapeutic approaches. In order to be applicable in a clinical setting,
      predictive biomarkers must be carefully shepherded through a step-wise, highly
      regulated developmental process. Volume I of this two-volume document focused on
      the pre-analytical and analytical phases of the biomarker development process, by
      providing background, examples and "good practice" recommendations. In the
      current Volume II, the focus is on the clinical validation, validation of
      clinical utility and regulatory considerations for biomarker development.
      Together, this two volume series is meant to provide guidance on the entire
      biomarker development process, with a particular focus on the unique aspects of
      developing immune-based biomarkers. Specifically, knowledge about the challenges
      to clinical validation of predictive biomarkers, which has been gained from
      numerous successes and failures in other contexts, will be reviewed together with
      statistical methodological issues related to bias and overfitting. The different
      trial designs used for the clinical validation of biomarkers will also be
      discussed, as the selection of clinical metrics and endpoints becomes critical to
      establish the clinical utility of the biomarker during the clinical validation
      phase of the biomarker development. Finally, the regulatory aspects of submission
      of biomarker assays to the U.S. Food and Drug Administration as well as
      regulatory considerations in the European Union will be covered.

PMID- 27891225
TI  - Unraveling the role of preexisting immunity in prostate cancer patients
      vaccinated with a HER-2/neu hybrid peptide.
AB  - BACKGROUND: Cancer vaccines aim at eliciting not only an immune response against
      specific tumor antigens, but also at enhancing a preexisting immunity against the
      tumor. In this context, we recently reported on the levels of preexisting
      immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide
      (AE37), during a phase I clinical trial. The purpose of the current study was to
      correlate between preexisting immunity to the native HER-2 peptide, AE36, and
      expression of HLA-A2 and -A24 molecules with the clinical outcome. Additionally,
      we investigated the ability of the AE37 vaccine to induce an antitumor immune
      response against other tumor associated antigens, not integrated in the vaccine
      formulation, with respect to the clinical response. METHODS: We analyzed prostate
      cancer patients who were vaccinated with the AE37 vaccine [Ii-Key-HER-2/neu(776
      790) hybrid peptide vaccine (AE37), which is a MHC class II long peptide vaccine
      encompassing MHC class I epitopes, during a phase I clinical trial. Preexisting
      immunity to the native HER-2/neu(776-790) (AE36) peptide was assessed by IFNgamma
      response or dermal reaction at the inoculation site. Antigen specificity against
      other tumor antigens was defined using multimer analysis. Progression free
      survival (PFS) was considered as the patients' clinical outcome. Two-tailed
      Wilcoxon signed rank test at 95 % confidence interval was used for statistical
      evaluation at different time points and Kaplan-Meier curves with log-rank (Mantel
      Cox) test were used for the evaluation of PFS. RESULTS: Preexisting immunity to
      AE36, irrespectively of HLA expression, was correlated with longer PFS. Specific
      CD8+ T cell immunity against E75 and PSA146-151 (HLA-A2 restricted), as well as,
      PSA153-161 (HLA-A24 restricted) was detected at relatively high frequencies which
      were further enhanced during vaccinations. Specific immunity against PSA153-161
      correlated with longer PFS in HLA-A24+ patients. However, HLA-A2+ patients with
      high preexisting or vaccine-induced immunity to E75, showed a trend for shorter
      PFS. CONCLUSIONS: Our data cast doubt on whether preexisting immunity or epitope
      spreading specific for HLA-class I-restricted peptides can actually predict a
      favorable clinical outcome. They also impose that preexisting immunity to long
      vaccine peptides, encompassing both HLA class II and I epitopes should be
      considered as an important prerequisite for the improvement of future
      immunotherapeutic protocols. Protocol ID Code: Generex-06-07 National
      Organization for Medicines (EOF) ID Code: IS-107-01-06 NEC Study Code:
      EED107/1/06 EudraCT Number: 2006-003299-37 Date of registration: 07/06/2006 Date
      of enrolment of the first participant to the trial: Nov 1st, 2007.

PMID- 27891228
TI  - A probabilistic algorithm to process geolocation data.
AB  - BACKGROUND: The use of light level loggers (geolocators) to understand movements
      and distributions in terrestrial and marine vertebrates, particularly during the
      non-breeding period, has increased dramatically in recent years. However,
      inferring positions from light data is not straightforward, often relies on
      assumptions that are difficult to test, or includes an element of subjectivity.
      RESULTS: We present an intuitive framework to compute locations from twilight
      events collected by geolocators from different manufacturers. The procedure uses
      an iterative forward step selection, weighting each possible position using a set
      of parameters that can be specifically selected for each analysis. The approach
      was tested on data from two wide-ranging seabird species - black-browed albatross
      Thalassarche melanophris and wandering albatross Diomedea exulans - tracked at
      Bird Island, South Georgia, during the two most contrasting periods of the year
      in terms of light regimes (solstice and equinox). Using additional information on
      travel speed, sea surface temperature and land avoidance, our approach was
      considerably more accurate than the traditional threshold method (errors reduced
      to medians of 185 km and 145 km for solstice and equinox periods, respectively).
      CONCLUSIONS: The algorithm computes stable results with uncertainty estimates,
      including around the equinoxes, and does not require calibration of solar angles.
      Accuracy can be increased by assimilating information on travel speed and
      behaviour, as well as environmental data. This framework is available through the
      open source R package probGLS, and can be applied in a wide range of biologging
      studies.

PMID- 27891229
TI  - Nicotine replacement therapy for agitation and delirium management in the
      intensive care unit: a systematic review of the literature.
AB  - BACKGROUND: Active smokers are prevalent within the intensive care setting and
      place a significant burden on healthcare systems. Nicotine withdrawal due to
      forced abstinence on admission may contribute to increased agitation and delirium
      in this patient group. The aim of this systematic review was to determine whether
      management of nicotine withdrawal, with nicotine replacement therapy (NRT),
      reduces agitation and delirium in critically ill patients admitted to the
      intensive care unit (ICU). METHODS: The following sources were used in this
      review: MEDLINE, EMBASE, and CINAHL Plus databases. Included studies reported
      delirium or agitation outcomes in current smokers, where NRT was used as
      management of nicotine withdrawal, in the intensive care setting. Studies were
      included regardless of design or number of participants. Data were extracted on
      ICU classification; study design; population baseline characteristics; allocation
      and dose of NRT; agitation and delirium assessment methods; and the frequency of
      agitation, delirium, and psychotropic medication use. RESULTS: Six studies were
      included. NRT was mostly prescribed for smokers with heavier smoking histories.
      Three studies reported an association between increased agitation or delirium and
      NRT use; one study could not find any significant benefit or harm from NRT use;
      and two described a reduction of symptomatic nicotine withdrawal. A lack of
      consistent and validated assessment measures, combined with limitations in the
      quality of reported data, contribute to conflicting results. CONCLUSIONS: Current
      evidence for the use of NRT in agitation and delirium management in the ICU is
      inconclusive. An evaluation of risk versus benefit on an individual patient basis
      should be considered when prescribing NRT. Further studies that consider
      prognostic balance, adjust for confounders, and employ validated assessment tools
      are urgently needed.

PMID- 27891227
TI  - Society for Immunotherapy of Cancer consensus statement on immunotherapy for the
      treatment of renal cell carcinoma.
AB  - Immunotherapy has produced durable clinical benefit in patients with metastatic
      renal cell cancer (RCC). In the past, patients treated with interferon-alpha
      (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which
      have lasted for multiple decades. More recently, a large number of new agents
      have been approved for RCC, several of which attack tumor angiogenesis by
      inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR),
      as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR).
      Additionally, a new class of immunotherapy agents, immune checkpoint inhibitors,
      is emerging and will play a significant role in the treatment of patients with
      RCC. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a Task
      Force, which met to consider the current role of approved immunotherapy agents in
      RCC, to provide guidance to practicing clinicians by developing consensus
      recommendations and to set the stage for future immunotherapeutic developments in
      RCC.

PMID- 27891230
TI  - Development of a population pharmacokinetic model of prucalopride in children
      with functional constipation.
AB  - A recent phase 3 trial of prucalopride in children with functional constipation
      (SPD555-303 ClinicalTrials.gov Identifier: NCT01330381) reported negative
      efficacy results. Here, we developed a population pharmacokinetic (PK) model of
      prucalopride in children to assess prucalopride exposure in SPD555-303. An
      initial population PK model in children was developed based on sampled single
      dose data from a phase 1 study (PRU-USA-12). This model was subsequently updated
      with sampled data from SPD555-303 and used to simulate plasma concentration-time
      profiles for children aged 6 months to 18 years who were treated once daily with
      prucalopride 0.02, 0.04, or 0.06 mg kg-1 (maximum dose, 2 mg). Simulated PK
      profiles were compared with those of adults at the recommended dose of 2 mg once
      daily. Data were available from 38 patients (median age, 8.5 years) in PRU-USA-12
      and 137 patients (median age, 7.9 years) in SPD555-303. Mean (range) area under
      the plasma concentration-time curve (AUC) at steady state was 62.3 (40.5-82.7) ng
      mL-1 h (dose, 0.03 mg kg-1) in PRU-USA-12 and 100.3 (22.7-286.0) ng mL-1 h (dose,
      0.04 mg kg-1; maximum, 2 mg) in SPD555-303. Prucalopride 0.04 mg kg-1 once daily
      in children produced similar maximum plasma concentrations and approximately 10%
      lower AUC compared with adults receiving 2 mg once daily. This population PK
      analysis indicates that the PK profile of prucalopride in children in SPD555-303
      was similar to that observed in adults. The negative efficacy results of SPD555
      303 cannot be explained by differences in prucalopride exposure between children
      and adults.

PMID- 27891231
TI  - A pharmacokinetic evaluation and metabolite identification of the GHB receptor
      antagonist NCS-382 in mouse informs novel therapeutic strategies for the
      treatment of GHB intoxication.
AB  - Gamma-aminobutyric acid (GABA) is an endogenous inhibitory neurotransmitter and
      precursor of gamma-hydroxybutyric acid (GHB). NCS-382 (6,7,8,9-tetrahydro-5
      hydroxy-5H-benzo-cyclohept-6-ylideneacetic acid), a known GHB receptor
      antagonist, has shown significant efficacy in a murine model of succinic
      semialdehyde dehydrogenase deficiency (SSADHD), a heritable neurological disorder
      featuring chronic elevation of GHB that blocks the final step of GABA
      degradation. NCS-382 exposures and elimination pathways remain unknown;
      therefore, the goal of the present work was to obtain in vivo pharmacokinetic
      data in a murine model and to identify the NCS-382 metabolites formed by mouse
      and human. NCS-382 single-dose mouse pharmacokinetics were established following
      an intraperitoneal injection (100, 300, and 500 mg/kg body weight) and metabolite
      identification was conducted using HPLC-MS/MS. Kinetic enzyme assays employed
      mouse and human liver microsomes. Upon gaining an understanding of the NCS-382
      clearance mechanisms, a chemical inhibitor was used to increase NCS-382 brain
      exposure in a pharmacokinetic/pharmacodynamic study. Two major metabolic pathways
      of NCS-382 were identified as dehydrogenation and glucuronidation. The Km for the
      dehydrogenation pathway was determined in mouse (Km = 29.5 +/- 10.0 MUmol/L) and
      human (Km = 12.7 +/- 4.8 MUmol/L) liver microsomes. Comparable parameters for
      glucuronidation were >100 MUmol/L in both species. Inhibition of NCS-382
      glucuronidation, in vivo, by diclofenac resulted in increased NCS-382 brain
      concentrations and protective effects in gamma-butyrolactone-treated mice. These
      initial evaluations of NCS-382 pharmacokinetics and metabolism inform the
      development of NCS-382 as a potential therapy for conditions of GHB elevation
      (including acute intoxication & SSADHD).

PMID- 27891232
TI  - Prevalence of transfusion transmissible infections in blood donors of Pakistan.
AB  - BACKGROUND: Transfusion-transmitted infections threaten the safety of patients
      requiring blood transfusion, which in turn imposes serious challenges for the
      availability of safe blood products that are still affordable in health care
      systems with limited resources. The aim of the study was to determine the
      prevalence of transfusion-transmitted infections in blood donors and to evaluate
      the demographic characteristics of reactive and non-reactive blood donors.
      METHODS: A prospective cohort study was conducted at our institute in Karachi,
      Pakistan. Donors were required to fill a detailed questionnaire and were screened
      for Hepatitis B, Hepatitis C, Human immunodeficiency viruses, Syphilis and
      Malaria by ELISA and thick film (malaria). RESULTS: Of the 16,602 blood donors,
      16,557 were males and 45 females (mean age 28.6 +/- 2). Nine hundred and seventy
      three (5.8%) donations were reactive in any screening assay, with 58 (0.35%)
      donations reacting in more than one assay. The prevalence of Hepatitis B,
      Hepatitis C, Human immunodeficiency viruses, Syphilis and Malaria was found to be
      1.84, 1.7, 0.04, 2.1 and 0.07% respectively. Characteristics among the infections
      were evaluated and it was found that unmarried donors had a higher chance to be
      infected by Hepatitis B virus and Syphilis as compared to the other infections.
      On the other hand, construction workers and married donors were at more risk to
      be infected by Syphilis rather than the other infections. In case of co
      infections, personnel with different occupations and marital status were infected
      by more than one pathogen. CONCLUSION: A substantial percentage of the blood
      donor's harbored transfusion-transmitted infections. Prevention of TTIs should be
      the main goal right now. There is a need for stringent selection of blood donors
      with the emphasis on getting voluntary donations and comprehensive screening of
      donor's blood for TTIs using standard methods to ensure the safety of blood
      recipient.

PMID- 27891233
TI  - Effectiveness and implementation of a community-based prevention programme
      targeting anabolic androgenic steroid use in gyms: study protocol of a quasi
      experimental control group study.
AB  - BACKGROUND: During the past decades, concerns about increased anabolic androgenic
      steroid (AAS) use among recreational sportspeople have been raised, yet there is
      a paucity of AAS prevention efforts targeting this group. Accordingly, doping
      prevention efforts aimed at gyms have been recommended. The overall objective of
      the present project is to examine a prevention programme named 100% Pure Hard
      Training (100% PHT), which targets AAS use among recreational sportspeople
      training in gyms. Specifically, the project aims to: 1) assess the prevalence of
      AAS, and its associations with alcohol, illicit drugs, and nutritional
      supplements use; 2) examine whether 100% PHT can decrease AAS use in gyms, and 3)
      provide insights into which factors facilitate and/or impede implementation of
      the programme. METHODS/DESIGN: The intervention group consists of 27 gyms, and 27
      gyms serve as controls. Intervention gyms take part in 100% PHT, a community
      based programme involving several components: (a) training of key stakeholders
      (i.e., gym staff, gym owners, local police, and municipal prevention
      coordinators) regarding AAS use; (b) developing an action plan for AAS prevention
      for each gym; (c) certification of gyms that follow 100% PHT; (d) cooperative
      relationship between stakeholders; (e) annual follow-up of gyms. The project
      consists of two studies: Study A will examine the prevalence of AAS use and the
      effectiveness of 100% PHT (aims 1 and 2), and data for Study A will be collected
      using questionnaires distributed to gym attendees at two assessment points:
      baseline (pre-intervention) and follow-up (post-intervention). Study B will
      evaluate the implementation of 100% PHT (aim 3), and semi-structured interviews
      with participating stakeholders will be carried out post-intervention.
      DISCUSSION: Knowledge gained from the present project can be used to develop
      community-based doping prevention efforts aimed at recreational sportspeople
      training in gyms. Furthermore, it can provide insights into which factors are
      important for successful implementation of AAS prevention programmes that target
      gyms. Results are also expected to yield information on the prevalence of AAS use
      as well as associations between the use of AAS and other licit and illicit
      substances, including nutritional supplements, among recreational sportspeople.
      TRIAL REGISTRATION: The study was registered retrospectively at isrctn.com
      (Identifier: ISRCTN11655041; Registration date: 3 November 2016;).

PMID- 27891234
TI  - Normative values for musculoskeletal- and neuromotor fitness in apparently
      healthy Norwegian adults and the association with obesity: a cross-sectional
      study.
AB  - BACKGROUND: Up-to-date research on musculoskeletal- and neuromotor fitness (MSMF)
      is lacking. The aims of the present paper were to a) establish normative values
      of MSMF by gender and age, and b) to assess how much of the variance in MSMF can
      be explained by obesity in adults. METHODS: A random selection of 726 Norwegians
      (20-65 years) participated in a national cross-sectional study. Muscular
      endurance, muscular strength, explosive power, flexibility and balance were
      assessed in addition to waist circumference (WC). RESULTS: Females displayed
      significantly higher scores compared to males on muscular endurance of the back
      extensors and on the flexibility tests (p < 0.001). Males displayed significantly
      higher scores than females (p < 0.001) on handgrip strength, modified push-ups,
      and explosive power. An inverse association was found between age and all MSMF
      scores for females (Beta:-0.06-(-0.92), p <= 0.044) and males (Beta:-0.15-(0.91),
      p <= 0.006), where younger participants displayed higher test scores on all MSMF
      tests, compared to older participants. Furthermore, participants showing higher
      scores on WC displayed lower scores on the following MSMF tests for both females
      and males: muscular endurance of the back extensors, balance, flexibility of the
      shoulder, and explosive power (p < 0.001). Additionally, male participants with
      higher WC scores showed lower scores on muscular endurance of the upper body and
      flexibility of the hamstrings compared to males with lower WC scores (p < 0.001).
      CONCLUSIONS: The data provide normative values of MSMF for adults based on age
      and gender, and support an inverse relationship of MSMF to age and WC.

PMID- 27891235
TI  - Interaction and medical inducement between pharmaceutical representatives and
      physicians: a meta-synthesis.
AB  - BACKGROUND: It has been proven that the interaction between pharmaceutical
      representatives and physicians can directly influence the latter's prescribing
      behaviour. This meta-synthesis aims to explore the available studies regarding
      the nature of the interaction that takes place between pharmaceutical
      representatives and physicians. It highlights the different aspects of that
      interaction by investigating the reasons why these meetings happen in the first
      place, their benefits and drawbacks and their impact on patients' health and,
      ultimately, the health of the public. METHODS: A search for published articles
      was conducted in April 2015. Three databases (PubMed, Ovid Medline, and ProQuest)
      were searched for articles published between January 2000 and April 2015. Authors
      worked autonomously and in pairs to select eligible articles. In this case, the
      meta-synthesis approach was used to develop a fuller understanding and to
      facilitate new knowledge by bringing together qualitative findings on physician
      PR interaction. 'Meta-synthesis' is the process of amalgamation of a group of
      similar studies with the aim of developing an explanation for their findings
      (Walsh and Downe, J Advanc Nurs 50: 204-211, 2005). A thematic content analysis
      was conducted on the 15 included full text articles (qualitative and quantitative
      studies) whereby the original authors' understanding of key concepts in each
      study was identified and listed in a summary form in the data extraction sheet
      under "key findings" column. These findings were then juxtaposed to identify
      homogeneity and dissonance (Walsh and Downe, J Advanc Nurs 50: 204-211, 2005).
      Homogenous findings were then coded together on a different data extraction table
      to form a theme. RESULTS: A total of 15 articles met the inclusion criteria and
      were included in this meta-synthesis;six from the United States, two from Libya,
      and one each from Turkey, Peru, India, Germany, the United Kingdom, Yemen, and
      Japan. Six main themes were derived from the included articles: 1-the frequency
      of pharmaceutical representatives' visits, 2-the perceived ethical acceptability
      of the interactions between pharmaceutical representatives and physicians, 3-the
      attitudes held by physicians towards visits by pharmaceutical representatives, 4
      their perception of the effect of such visits on prescription patterns, 5-reasons
      to accept or reject pharmaceutical representatives, and lastly, 6-guidelines.
      CONCLUSIONS: The physicians referred to pharmaceutical representatives as
      efficient and convenient information resources and were willing to meet them and
      accept their gifts. It was also evident that most physicians believed that their
      prescribing would not be influenced by pharmaceutical representatives.

PMID- 27891236
TI  - Morbidity patterns among the welders of eastern Nepal: a cross-sectional study.
AB  - BACKGROUND: Welding process has many hazards that the welders are exposed to
      resulting in numbers of health effects and diseases. Safety measures and
      practices among welders are important ways of preventing or reducing the health
      hazards associated with this occupation. We conducted this study to find out the
      morbidity patterns among the welders working in eastern Nepal. METHODS: A cross
      sectional study was conducted among 300 welders using semi structured
      questionnaire. Morbidity categories were classified based on symptoms experienced
      in past 6 months. RESULTS: All the welders learned welding by apprenticeship,
      without any formal health and safety training. Injury was the most common problem
      at work followed by skin problems and eye symptoms. Age of the welders, duration
      of employment & welding hours per day were associated with the morbidities among
      the welders. CONCLUSIONS: There is a need for occupational health services for
      welders in Nepal. While further research may be required to make policy
      recommendations, the current study provides a baseline morbidity burden among
      these welders to look for interventions to promote health and safety at work for
      this neglected group of workers in Nepal.

PMID- 27891237
TI  - The impact of fire suppression tasks on firefighter hydration: a critical review
      with consideration of the utility of reported hydration measures.
AB  - BACKGROUND: Firefighting is a highly stressful occupation with unique physical
      challenges, apparel and environments that increase the potential for dehydration.
      Dehydration leaves the firefighter at risk of harm to their health, safety and
      performance. The purpose of this review was to critically analyse the current
      literature investigating the impact of fighting 'live' fires on firefighter
      hydration. METHODS: A systematic search was performed of four electronic
      databases for relevant published studies investigating the impact of live fire
      suppression on firefighter hydration. Study eligibility was assessed using strict
      inclusion and exclusion criteria. The included studies were critically appraised
      using the Downs and Black protocol and graded according to the Kennelly grading
      system. RESULTS: Ten studies met the eligibility criteria for this review. The
      average score for methodological quality was 55 %, ranging from 50 % ('fair'
      quality) to 61 % ('good' quality) with a 'substantial agreement' between raters
      (k = .772). Wildfire suppression was considered in five studies and structural
      fire suppression in five studies. Results varied across the studies, reflecting
      variations in outcome measures, hydration protocols and interventions. Three
      studies reported significant indicators of dehydration resulting from structural
      fire suppression, while two studies found mixed results, with some measures
      indicating dehydration and other measures an unchanged hydration status. Three
      studies found non-significant changes in hydration resulting from wildfire
      firefighting and two studies found significant improvements in markers of
      hydration. Ad libitum fluid intake was a common factor across the studies finding
      no, or less severe, dehydration. CONCLUSIONS: The evidence confirms that
      structural and wildfire firefighting can cause dehydration. Ad libitum drinking
      may be sufficient to maintain hydration in many wildfire environments but
      possibly not during intense, longer duration, hot structural fire operations.
      Future high quality research better quantifying the effects of these influences
      on the degree of dehydration is required to inform policies and procedures that
      ensure firefighter health and safety.

PMID- 27891238
TI  - The effect of long working hours on 10-year risk of coronary heart disease and
      stroke in the Korean population: the Korea National Health and Nutrition
      Examination Survey (KNHANES), 2007 to 2013.
AB  - BACKGROUND: Recently, the emergence of long working hours and the associated
      conditions such as coronary heart disease (CHD) and stroke have gained attention.
      The aim of this study was to investigate the association between long working
      hours and the 10-year-risk of CHD and stroke, estimated by Jee's health risk
      appraisal model for ischemic heart disease. METHODS: We analyzed data from
      Koreans who randomly enrolled in Korean National Health and Nutrition Examination
      Survey 2008-2012 and finally included 13,799 participants. The participants were
      classified as per their working hours: 0-30 h/week, 31-39 h/week, 40 h/week, 41
      50 h/week, 51-60 h/week, 61-70 h/week, 71-80 h/week, and >80 h/week. The risks
      for CHD and stroke were determined using Jee's health risk-appraisal model.
      Multiple logistic regression was used to analyze the association between working
      hours and 10-year risk for CHD. RESULTS: The 10-year risks for CHD and stroke
      were significantly and positively associated with working hours in both men and
      women. Furthermore, higher risks for CHD and stroke were associated with longer
      working hours in women. CONCLUSION: Long working hours are significantly
      associated with the risks of CHD and stroke, estimated by Jee's health risk
      appraisal model. This study suggests the need for proper management of working
      hours to reduce CHD risk and stroke risk in the Korean population.

PMID- 27891239
TI  - Two cases of methyl alcohol intoxication by sub-chronic inhalation and dermal
      exposure during aluminum CNC cutting in a small-sized subcontracted factory.
AB  - BACKGROUND: Methyl alcohol poisoning has been mainly reported in community. Two
      cases of methyl alcohol poisoning occurred in a small-sized subcontracted factory
      which manufactured smartphone parts in Korea. CASE PRESENTATION: One young female
      patient presented with dyspnea and visual disturbance. Another young male patient
      presented with visual disturbance and myalgia. They treated with sodium
      bicarbonate infusion and hemodialysis for metabolic acidosis. In addition, he
      received ethyl alcohol per oral treatment. Her and his urinary methyl alcohol
      concentration was detected as 7.632 mg/L, 46.8 mg/L, respectively, although they
      were treated hemodialysis. Results of the working environment measurement showed
      that the concentration of methyl alcohol (1030.1-2220.5 ppm) in the air exceeded
      the time weighted average (200 ppm). They were diagnosed with optic neuropathy
      due to methyl alcohol poisoning and still have visual impairment. CONCLUSIONS:
      Workers who hired as dispatched employees in a small-sized subcontracted factory
      were exposed to high concentrations of methyl alcohol. The workplace had poor
      ventilation system. In addition, workers did not wear proper personal protect
      equipment. Working environment measurement and annual chekups for workers were
      not performed. They were in a blind spot to occupational safety and health. More
      attention is needed to protect vulnerable workers' health.

PMID- 27891240
TI  - Differences in the clinical manifestations and short-term prognosis of acute
      cerebral infarction after exposure to Agent Orange.
AB  - BACKGROUND: Agent Orange (AO) is the code name for one of the herbicides and
      defoliants used in the Vietnam War. Studies conducted thus far show a significant
      correlation between AO and the occurrence of cardiovascular diseases. But there
      is little data on the association between AO and stroke, and limited studies have
      targeted patient groups exposed to AO. METHOD: Bohun medical center Institutional
      Review Board (IRB) approved the study. (ID: 341) We studied patients with acute
      ischemic stroke within 7 days of onset in VHS medical center and 4 other general
      hospitals. Among them, 91 consecutive patients with previous exposure to AO were
      evaluated. For controlled group, 288 patients with no history of AO exposure were
      chosen. RESULT: There were 49 (44.0 %) DM patient with a higher frequency in the
      exposure group (93 (32.3 %) in control P = 0.045). There were 6 (6.6 %)
      hyperlipidemia in exposure group and 69 (24.0 %) in control. (P < 0.002). Small
      vessel occlusion was the most common subtype (36, 39.6 %) in exposure group but
      in control group, the large artery atherosclesosis was (120, 41.7 %) (P = 0.014).
      The NIHSS of the exposure group on admission showed lower scores (median values,
      2 and 4, respectively; P = 0.003). The median mRS was 1 for the exposure group
      and 2 for the control group, at discharge and after 3 months. After 3 months of
      discharge, 55 (60.4 %) in the exposure group and 171 (59.4 %) in the control
      group showed below mRS 1 (P = 0.001). CONCLUSION: This study targeted patients
      who are Vietnam veteran. There is some difference in vascular risk factors and
      clinical manifestations suggest AO exposure has contributed to a certain extent
      to the stroke.

PMID- 27891241
TI  - No evidence of prenatal diversifying selection at locus or supertype levels in
      the dog MHC class II loci.
AB  - BACKGROUND: Despite decades of studying, the mechanisms maintaining high
      diversity in the genes of the Major Histocompatibility Complex (MHC) are still
      puzzling scientists. In addition to pathogen recognition and other functions, MHC
      molecules may act prenatally in mate choice and in maternal-foetal interactions.
      These interactions are potential selective mechanisms that increase genetic
      diversity in the MHC. During pregnancy, immune response has a dual role: the
      foetus represents foreign tissue compared to mother, but histo-incompatibility is
      required for successful pregnancy. We have studied the prenatal selection in MHC
      class II loci (DLA-DQA1, DLA-DQB1 and DLA-DRB1) in domestic dogs by comparing the
      observed and expected offspring genotype proportions in 110 dog families. Several
      potential selection targets were addressed, including the peptide-binding site,
      the MHC locus, three-locus haplotype and supertype levels. For the supertype
      analysis, the first canine supertype classification was created based on in
      silico analysis of peptide-binding amino-acid polymorphism. RESULTS: In most loci
      and levels, no deviation from the expected genotype frequencies was observed.
      However, one peptide-binding site in DLA-DRB1 had an excess of heterozygotes
      among the offspring. In addition, if the father shared a DLA-DRB1 allele with the
      mother, that allele was inherited by the offspring more frequently than expected,
      suggesting the selective advantage of a histo-compatible foetus, in contrast to
      our expectations. CONCLUSIONS: We conclude that there is some evidence of post
      copulatory selection at nucleotide site level in the MHC loci of pet dogs. But
      due to no indication of selection at locus, three-locus, or supertype levels, we
      estimated that the prenatal selection coefficient is less than 0.3 in domestic
      dogs and very likely other factors are more important in maintaining the genetic
      diversity in MHC loci.

PMID- 27891242
TI  - Community factors related to healthy eating & active living in counties with
      lower than expected adult obesity rates.
AB  - BACKGROUND: Adult obesity rates in the United States have reached epidemic
      proportions, yet vary considerably across states and counties. We sought to
      explore community-level factors that may be associated with reduced adult obesity
      rates at the county level. METHODS: We identified six U.S. counties that were
      positive deviants for adult obesity and conducted semi-structured interviews with
      community leaders and government officials involved in efforts to promote
      healthier lifestyles. Using site visits and in-depth qualitative interviews, we
      identified several recurrent themes and strategies. RESULTS: Participants: 1)
      developed a nuanced understanding of their communities; 2) recognized the complex
      nature of obesity, and 3) implemented a county-wide strategic approach for
      promoting healthy living. This county-wide approachwas used to a) break down
      silos and build partnerships, b) access community resources and connections, and
      c) transfer ownership to community members. CONCLUSIONS: We found that county
      leaders focused on establishing a county-wide structure to connect and support
      community-led initiatives to promote healthy living, reduce obesity, and foster
      sustainability. Findings from this study can help inform county-level efforts to
      improve healthy living and combat the multi-faceted challenges of adult obesity
      across the U.S.

PMID- 27891243
TI  - A comprehensive musculoskeletal and peripheral nervous system assessment of war
      related bilateral upper extremity amputees.
AB  - BACKGROUND: Upper limb amputations are one of the unpleasant war injuries that
      armed forces are exposed to frequently. The present study aimed to assess the
      musculoskeletal and peripheral nervous systems in Iraq-Iran war veterans with
      bilateral upper extremity amputation. METHODS: The study consisted of taking a
      history and clinical examinations including demographic data, presence and
      location of pain, level of amputation, passive and active ranges of movement of
      the joints across the upper and lower extremities and spine, manual palpation,
      neurological examination, blood circulation pulses and issues related to a
      prosthetic limb. In this study, 103 Iranian bilateral upper extremity amputees
      (206 amputations) from the Iran-Iraq war were evaluated, and a detailed
      questionnaire was also administered. RESULTS: The most common level of amputation
      was the finger or wrist level (108, 52.4 %). Based on clinical examination, we
      found high frequencies of limited active and passive joint range of movement
      across the scapula, shoulder, elbow, wrist and metacarpophalangeal,
      interphalangeal and thumb joints. Based on muscle strength testing, we found
      varying degrees of weakness across the upper limbs. Musculoskeletal disorders
      included epicondylitis (65, 31.6 %), rotator cuff injury (24, 11.7 %), bicipital
      tendonitis (69, 33.5 %), shoulder drop (42, 20.4 %) and muscle atrophy (19, 9.2
      %). Peripheral nerve disorders included carpal tunnel syndrome in 13 (6.3 %) and
      unilateral brachial plexus injury in 1 (1 %). Fifty-three (51.5 %) were diagnosed
      with facet joint syndrome at the level of the cervical spine (the most frequent
      site). Using a prosthesis was reported by 65 (63.1 %), both left and right sides.
      The back was the most common site of pain (71.8 %). CONCLUSION: The high
      prevalence of neuro-musculoskeletal disorders among bilateral upper extremity
      amputees indicates that they need regular rehabilitation care.

PMID- 27891245
TI  - Genetic diversity of Halla horses using microsatellite markers.
AB  - BACKGROUND: Currently about 26,000 horses are breeding in Korea and 57.2% (14,776
      horses) of them are breeding in Jeju island. According to the statistics
      published in 2010, the horses breeding in Jeju island are subdivided into Jeju
      horse (6.1%), Thoroughbred (18.8%) and Halla horse (75.1%). Halla horses are
      defined as a crossbreed between Jeju and Thoroughbred horses and are used for
      horse racing, horse riding and horse meat production. However, little research
      has been conducted on Halla horses because of the perception of crossbreed and
      people's weighted interest toward Jeju horses. METHOD: Using 17 Microsatellite
      (MS) Markers recommended by International Society for Animal Genetics (ISAG),
      genomic DNAs were extracted from the hair roots of 3,880 Halla horses breeding in
      Korea and genetic diversity was identified by genotyping after PCR was performed.
      RESULTS AND CONCLUSION: In average, 10.41 alleles (from 6 alleles in HTG7 to 17
      alleles in ASB17) were identified after the analysis using 17 MS Markers. The
      mean value of Hobs was 0.749 with a range from 0.612(HMS1) to 0.857(ASB2). Also,
      it was found that Hexp and PIC values were lowest in HMS1 (0.607 and 0.548,
      respectively), and highest in LEX3(0.859 and 0.843, respectively), and the mean
      value of Hexp was 0.760 and that of PIC was 0.728. 17 MS markers used in this
      studies were considered as appropriate markers for the polymorphism analysis of
      Halla horses. The frequency for the appearance of identical individuals was 5.90
      * 10-20 when assumed as random mating population and when assumed as half-sib and
      full-sib population, frequencies were 4.08 * 10-15 and 3.56 * 10-8, respectively.
      Based on these results, the 17 MS markers can be used adequately for the
      Individual Identification and Parentage Verification of Halla horses. Remarkably,
      allele M and Q of ASB23 marker, G of HMS2 marker, H and L of HTG6 marker, L of
      HTG7 marker, E of LEX3 marker were the specific alleles unique to Halla horses.

PMID- 27891246
TI  - Two-headed mutants of the lamprey, a basal vertebrate.
AB  - BACKGROUND: This is the first report of two-headed (bicephaly) lamprey twins.
      Although lampreys sit at a crucial phylogenetic position, there are only a few
      reports on their teratology and developmental abnormalities. RESULTS: Two-headed
      mutants were obtained by artificial fertilization in the laboratory as
      spontaneous occurrences. All mutants were derived from single fertilizations
      using single male and female gametes, suggestive of a genetic background. The
      anterio-posterior position of the axonal bifurcation and symmetricity varied in
      each mutant. Other malformations were coincidently observed, including
      pericardial edema, yolk sac edema and axial bending. Asymmetrical (lateral-
      branched) mutants displayed more severe abnormalities in the cranial nerves than
      symmetrical mutants. CONCLUSION: Two-headed mutants of the lamprey are described.
      These mutants have similar malformations to dorsal blastopore lip-transplanted
      lamprey embryos, suggesting that they could be generated by a disorder in head
      organizing activity.

PMID- 27891244
TI  - The effectiveness of regional cooling for paclitaxel-induced peripheral
      neuropathy.
AB  - BACKGROUND: There are currently no promising therapies available to treat or
      prevent peripheral neuropathy (PN) induced by anticancer drugs in a cumulative
      dose-dependent manner. In this study, we investigated the efficacy of regional
      cooling of hands and feet in preventing paclitaxel (PTX)-induced PN. METHODS:
      Patients with gynecologic cancer who received a tri-weekly cycle of chemotherapy
      including PTX at doses of 150-175 mg/m2 were included in this study. Regional
      cooling was performed by covering patient hands and feet with cold insulators
      during PTX administration (regional cooling group). The primary end-point was
      >=grade 2 PN evaluated by the Common Terminology Criteria for Adverse Events
      (CTCAE) v4.0. The secondary end-points were the frequency of PN therapeutic drug
      use, PTX dose reduction due to PN, and adverse events due to regional cooling.
      The efficacy of regional cooling was compared with data retrospectively extracted
      from the medical records of patients who did not receive regional cooling
      (control group). All end-points were evaluated for up to six cycles. RESULTS:
      There were 40 and 142 patients in the regional cooling and control groups,
      respectively. As a primary end-point, incidences of >=grade 2 PN in the fourth to
      sixth cycles were significantly lower than that in the cooling group (5.0-9.1 %
      vs. 19.8-31.6 %, p < 0.05 after the fourth cycle and p < 0.01 after the fifth
      cycle). Among secondary end-points, neither the use of PN therapeutic drugs nor
      the PTX dose reduction due to PN were significantly lower in the cooling group
      than in the control group (27.5 vs. 36.6 %, p = 0.378 and 5.0 vs. 3.5 %, p =
      0.645, respectively). There were no serious regional cooling-associated adverse
      events such as frostbite. CONCLUSIONS: Regional cooling of hands and feet during
      PTX administration might have good effectiveness and tolerability, suggesting
      this approach as a potentially effective supportive care to prevent PTX-induced
      PN. TRIAL REGISTRATION: The trial approval number in the institution; H25-26.
      Registered 5 June 2014.

PMID- 27891247
TI  - Librarians and Scientists Partner to Address Data Management: Taking
      Collaboration to the Next Level.
AB  - PURPOSE: This study looks at the changing way in which the Information Services
      Office (ISO) at the National Institute of Standards and Technology (NIST)
      provides services to NIST scientific and technical staff throughout their
      research and publishing cycles. These services include the more traditional
      services of a research library as well as publishing NIST technical reports and
      The Journal of Research of NIST, and preserving and exhibiting scientific
      instruments and other artifacts. ISO has always prided itself on having a close
      relationship with its customers, providing a high level of service, and
      developing new services to stay in front of NIST researcher needs. Through a
      concerted, strategic effort since the late 1990s, ISO has developed and promoted
      relationships with its key customers through its Lab Liaison Program.
      DESIGN/METHODOLOGY/APPROACH: This paper discusses the relationship ISO has
      developed with the Office of Data and Informatics (ODI), how this relationship
      was forged, and how this collaboration will serve as a model for working with the
      other labs and programs at NIST. It will also discuss the risks and opportunities
      of this new collaborative service model, how ISO positioned itself to become an
      equal partner with ODI in the exploration of solutions to data management issues,
      and the benefits of the relationship from ODI's perspective. FINDINGS: A pattern
      of strategic changes to the services and activities offered by the Lab Liaison
      program has put ISO in the position to collaborate as peers with researchers at
      NIST. ORIGINALITY/VALUE: This study provides an overview of how ISO made
      strategic decisions to incorporate non-traditional services to support data
      management at NIST.

PMID- 27891248
TI  - Synchrotron 4-dimensional imaging of two-phase flow through porous media.
AB  - Near real-time visualization of complex two-phase flow in a porous medium was
      demonstrated with dynamic 4-dimensional (4D) (3D + time) imaging at the 2-BM beam
      line of the Advanced Photon Source (APS) at Argonne National Laboratory.
      Advancing fluid fronts through tortuous flow paths and their interactions with
      sand grains were clearly captured, and formations of air bubbles and capillary
      bridges were visualized. The intense X-ray photon flux of the synchrotron
      facility made 4D imaging possible, capturing the dynamic evolution of both solid
      and fluid phases. Computed Tomography (CT) scans were collected every 12 s with a
      pixel size of 3.25 um. The experiment was carried out to improve understanding of
      the physics associated with two-phase flow. The results provide a source of
      validation data for numerical simulation codes such as Lattice-Boltzmann, which
      are used to model multi-phase flow through porous media.

PMID- 27891249
TI  - Protein Kinase C Epsilon Contributes to NADPH Oxidase Activation in a Pre
      Eclampsia Lymphoblast Cell Model.
AB  - Pre-eclampsia is a pregnancy-specific disorder characterised by hypertension and
      proteinuria, which in severe cases results in multi-system disturbances. The
      maternal syndrome is associated with a pro-inflammatory state, consisting of
      leukocyte activation, which is thought to contribute to the widespread
      endothelial dysfunction. We previously showed increased activation of NADPH
      oxidase in pre-eclampsia, in both neutrophils and B-lymphoblast cell lines (B
      LCLs). In this study, the mechanism by which NADPH oxidase activity is increased
      in pre-eclampsia was further investigated. NADPH oxidase activity was found to be
      increased in phorbol-12-myristate-13-acetate (PMA) stimulated B-LCLs isolated
      from women with pre-eclampsia. This correlated with an increase in protein kinase
      C (PKC) substrate phosphorylation, p47-phox phosphorylation (a regulatory
      component of NADPH oxidase) and p47-phox directed-kinase activity. Using ion
      exchange and hydroxyapatite chromatography we identified a major peak of PMA
      regulated p47-phox kinase activity. Chromatography fractions were probed for PKC
      isoforms. We found the major peak of p47-phox kinase activity could not be
      separated from the elution profile of PKC epsilon. Using a peptide inhibitor of
      PKC epsilon, PMA-induced reactive oxygen species (ROS) production could be
      reduced to that of a normal B-LCL. These data suggest a pro-inflammatory role for
      PKC epsilon in the pathogenesis of pre-eclampsia.

PMID- 27891250
TI  - Diabetic Macular Ischemia Diagnosis: Comparison between Optical Coherence
      Tomography Angiography and Fluorescein Angiography.
AB  - Purpose. To compare fluorescein angiography (FA) and optical coherence tomography
      angiography (OCTA) images of foveal avascular zone (FAZ) in patients with
      diabetic retinopathy (DR) with and without diabetic macular ischemia (DMI).
      Methods. The Wilcoxon signed-rank test was used to compare area measurements and
      p values of <0.05 were considered statistically significant. FA and OCTA images
      were independently graded by 2 observers that reached agreement regarding
      quantitative DMI according established protocols. The ischemic area was divided
      into "large" macular ischemia (superior to 0.32 mm2) and "small" (inferior to
      0.32 mm2) groups. Quantitative analyses of the FAZ were performed using custom
      software. Results. Thirty-four eyes from 34 diabetic patients were enrolled.
      Subjects with DMI presented a mean area on FA and OCTA of 0.68 +/- 0.53 mm2 and
      0.58 +/- 0.35 mm2, respectively (p = 0.1374). Patients without DMI presented a
      mean area on FA and OCTA of 0.19 +/- 0.67 mm2 and 0.20 +/- 0.79 mm2, respectively
      (p = 0.9594). The ICC for the FAZ measurements between the 2 observers on FA and
      OCTA was 0.96 and 0.92, respectively. Conclusion. OCTA represents a novel
      technique for the diagnosis of DMI and it may become an alternative to FA for
      this purpose.

PMID- 27891252
TI  - A Small Randomized Controlled Pilot Trial Comparing Mobile and Traditional Pain
      Coping Skills Training Protocols for Cancer Patients with Pain.
AB  - Psychosocial pain management interventions are efficacious for cancer pain but
      are underutilized. Recent advances in mobile health (mHealth) technologies
      provide new opportunities to decrease barriers to access psychosocial pain
      management interventions. The objective of this study was to gain information
      about the accessibility and efficacy of mobile pain coping skills training
      (mPCST) intervention delivered to cancer patients with pain compared to
      traditional in-person pain coping skills training intervention. This study
      randomly assigned participants (N = 30) to receive either mobile health pain
      coping skills training intervention delivered via Skype or traditional pain
      coping skills training delivered face-to-face (PCST-trad). This pilot trial
      suggests that mPCST is feasible, presents low burden to patients, may lead to
      high patient engagement, and appears to be acceptable to patients. Cancer
      patients with pain in the mPCST group reported decreases in pain severity and
      physical symptoms as well as increases in self-efficacy for pain management that
      were comparable to changes in the PCST-trad group (p's < 0.05). These findings
      suggest that mPCST, which is a highly accessible intervention, may provide
      benefits similar to an in-person intervention and shows promise for being
      feasible, acceptable, and engaging to cancer patients with pain.

PMID- 27891251
TI  - The Role of the Single Incision Laparoscopic Approach in Liver and Pancreatic
      Resectional Surgery.
AB  - Introduction. Single incision laparoscopic surgery (SILS) has gained increasing
      support over the last few years. The aim of this narrative review is to analyse
      the published evidence on the use and potential benefits of SILS in hepatic and
      pancreatic resectional surgery for benign and malignant pathology. Methods.
      Pubmed and Embase databases were searched using the search terms "single incision
      laparoscopic", "single port laparoscopic", "liver surgery", and "pancreas
      surgery". Results. Twenty relevant manuscripts for liver and 9 for pancreatic
      SILS resections were identified. With regard to liver surgery, despite the lack
      of comparative studies with other minimal invasive techniques, outcomes have been
      acceptable when certain limitations are taken into account. For pancreatic
      resections, when compared to the conventional laparoscopic approach, SILS
      produced comparable results with regard to intra- and postoperative parameters,
      including length of hospitalisation and complications. Similarly, the results
      were comparable to robotic pancreatectomies, with the exception of the longer
      operative time reported with the robotic approach. Discussion. Despite the
      limitations, the published evidence supports that SILS is safe and feasible for
      liver and pancreatic resections when performed by experienced teams in the
      tertiary setting. However, no substantial benefit has been identified yet,
      especially compared to other minimal invasive techniques.

PMID- 27891253
TI  - Cutaneous Human Papillomavirus Infection and Development of Subsequent Squamous
      Cell Carcinoma of the Skin.
AB  - The role of cutaneous human papillomavirus (HPV) infection in the development of
      subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically
      confirmed cases of SCC (n = 150) enrolled in a previously conducted case-control
      study were included in a retrospective cohort study to examine the association of
      cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC
      development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC
      tumors were available from the parent study. Incidence of subsequent SCC was
      estimated using person-years of follow up. Cox Proportional Hazards ratios were
      estimated to evaluate the associations of both, HPV seropositivity and HPV DNA
      positivity with subsequent SCC. The five year cumulative incidence of subsequent
      SCC was 72%. Seropositivity to cutaneous HPV was not associated with the risk of
      subsequent SCC (HR = 0.83, 95% CI = 0.41-1.67). Any beta HPV infection in EB was
      associated with reduced risk (HR = 0.30, 95% CI = 0.11-0.78) of subsequent SCC
      among cases who were positive for beta HPV DNA in tumor tissue. Infection with
      beta HPV type 2 (HR = 0.32, 95% CI = 0.12-0.86) in EB was associated with reduced
      risk of subsequent SCC among HPV DNA positive SCCs. In conclusion, beta HPV
      infection was inversely associated with the risk of subsequent SCC.

PMID- 27891254
TI  - Prostate Cancer: Epigenetic Alterations, Risk Factors, and Therapy.
AB  - Prostate cancer (PCa) is the most prevalent urological cancer that affects aging
      men in South Africa, and mechanisms underlying prostate tumorigenesis remain
      elusive. Research advancements in the field of PCa and epigenetics have allowed
      for the identification of specific alterations that occur beyond genetics but are
      still critically important in the pathogenesis of tumorigenesis. Anomalous
      epigenetic changes associated with PCa include histone modifications, DNA
      methylation, and noncoding miRNA. These mechanisms regulate and silence hundreds
      of target genes including some which are key components of cellular signalling
      pathways that, when perturbed, promote tumorigenesis. Elucidation of mechanisms
      underlying epigenetic alterations and the manner in which these mechanisms
      interact in regulating gene transcription in PCa are an unmet necessity that may
      lead to novel chemotherapeutic approaches. This will, therefore, aid in
      developing combination therapies that will target multiple epigenetic pathways,
      which can be used in conjunction with the current conventional PCa treatment.

PMID- 27891255
TI  - Comparison of Subjective and Objective Sleep Estimations in Patients with Bipolar
      Disorder and Healthy Control Subjects.
AB  - Background. Several studies have described but not formally tested discrepancies
      between subjective and objective measures of sleep. Study Objectives. To test the
      hypothesis that patients with bipolar disorder display a systematic bias to
      underestimate sleep duration and overestimate sleep latency. Methods. Actimetry
      was used to assess sleep latency and duration in 49 euthymic participants
      (bipolar = 21; healthy controls = 28) for 5-7 days. Participants simultaneously
      recorded estimated sleep duration and sleep latency on a daily basis via an
      online sleep diary. Group differences in the discrepancy between subjective and
      objective parameters were calculated using t-tests and corrected for multiple
      comparisons. Results. Patients with bipolar disorder significantly underestimated
      their sleep duration but did not overestimate their sleep latency compared to
      healthy controls. Conclusions. Studies utilizing diaries or questionnaires alone
      in patients with bipolar disorders may systematically underestimate sleep
      duration compared to healthy controls. The additional use of objective assessment
      methods such as actimetry is advisable.

PMID- 27891256
TI  - Scale-Dependent Signal Identification in Low-Dimensional Subspace: Motor Imagery
      Task Classification.
AB  - Motor imagery electroencephalography (EEG) has been successfully used in
      locomotor rehabilitation programs. While the noise-assisted multivariate
      empirical mode decomposition (NA-MEMD) algorithm has been utilized to extract
      task-specific frequency bands from all channels in the same scale as the
      intrinsic mode functions (IMFs), identifying and extracting the specific IMFs
      that contain significant information remain difficult. In this paper, a novel
      method has been developed to identify the information-bearing components in a low
      dimensional subspace without prior knowledge. Our method trains a Gaussian
      mixture model (GMM) of the composite data, which is comprised of the IMFs from
      both the original signal and noise, by employing kernel spectral regression to
      reduce the dimension of the composite data. The informative IMFs are then
      discriminated using a GMM clustering algorithm, the common spatial pattern (CSP)
      approach is exploited to extract the task-related features from the reconstructed
      signals, and a support vector machine (SVM) is applied to the extracted features
      to recognize the classes of EEG signals during different motor imagery tasks. The
      effectiveness of the proposed method has been verified by both computer
      simulations and motor imagery EEG datasets.

PMID- 27891257
TI  - MELAS Syndrome with Cardiac Involvement: A Multimodality Imaging Approach.
AB  - A 49-year-old man presented with chest pain, dyspnea, and lactic acidosis. Left
      ventricular hypertrophy and myocardial fibrosis were detected. The sequencing of
      mitochondrial genome (mtDNA) revealed the presence of A to G mtDNA point mutation
      at position 3243 (m.3243A>G) in tRNALeu(UUR) gene. Diagnosis of cardiac
      involvement in a patient with Mitochondrial Encephalomyopathy, Lactic Acidosis,
      and Stroke-like episodes syndrome (MELAS) was made. Due to increased risk of
      sudden cardiac death, cardioverter defibrillator was implanted.

PMID- 27891258
TI  - Lyme Carditis: An Interesting Trip to Third-Degree Heart Block and Back.
AB  - Carditis is an uncommon presentation of the early disseminated phase of Lyme
      disease. We present the case of a young female who presented with erythema
      migrans and was found to have first-degree heart block which progressed to
      complete heart block within hours. After receiving ceftriaxone, there was
      complete resolution of the heart block in sequential fashion. Our case
      illustrates the importance of early recognition and anticipation of progressive
      cardiac conduction abnormalities in patients presenting with Lyme disease.

PMID- 27891259
TI  - Neurocardiogenic Syncope and Supraventricular Tachycardia in Association with a
      Rare Congenital Aortic Valve Abnormality.
AB  - We report a case of a 26-year-old woman who presented with multiple episodes of
      syncope over a five-months period of time. Transthoracic echocardiogram had shown
      a normal functioning quadricuspid aortic valve (QAV) which was also confirmed on
      a transesophageal echocardiogram. Computed tomographic angiography of heart and
      coronary arteries showed the QAV with equal size of all aortic cusps and normal
      coronary arteries. Intermittent chest pain and palpitations warranted an exercise
      stress test. The stress test revealed normal aerobic exertion, with achievement
      of 101% of maximal peak heart rate. However, during peak stress, we noted a drop
      in her blood pressure significantly resulting in dizziness. No arrhythmias were
      noted during the stress test. With recurrent syncope episodes and palpitations,
      Holter monitoring was done, revealing supraventricular tachycardia (SVT). We
      discuss current available literature and coassociations with QAV. New association
      of QAV with SVT needs further analysis.

PMID- 27891260
TI  - Intravenous Vitamin C Administered as Adjunctive Therapy for Recurrent Acute
      Respiratory Distress Syndrome.
AB  - This case report summarizes the first use of intravenous vitamin C employed as an
      adjunctive interventional agent in the therapy of recurrent acute respiratory
      distress syndrome (ARDS). The two episodes of ARDS occurred in a young female
      patient with Cronkhite-Canada syndrome, a rare, sporadically occurring,
      noninherited disorder that is characterized by extensive gastrointestinal
      polyposis and malabsorption. Prior to the episodes of sepsis, the patient was
      receiving nutrition via chronic hyperalimentation administered through a long
      standing central venous catheter. The patient became recurrently septic with Gram
      positive cocci which led to two instances of ARDS. This report describes the
      broad-based general critical care of a septic patient with acute respiratory
      failure that includes fluid resuscitation, broad-spectrum antibiotics, and
      vasopressor support. Intravenous vitamin C infused at 50 mg per kilogram body
      weight every 6 hours for 96 hours was incorporated as an adjunctive agent in the
      care of this patient. Vitamin C when used as a parenteral agent in high doses
      acts "pleiotropically" to attenuate proinflammatory mediator expression, to
      improve alveolar fluid clearance, and to act as an antioxidant.

PMID- 27891261
TI  - Perioprosthetic and Implant-Supported Rehabilitation of Complex Cases: Clinical
      Management and Timing Strategy.
AB  - Treatment of complex perioprosthetic cases is one of the clinical challenges of
      everyday practice. Only a complete and thorough diagnostic setup may allow the
      clinician to formulate a realistic prognosis to select the abutments to support
      prosthetic rehabilitation. Clinical, radiographic, or laboratory parameters used
      separately are useless to correctly assign a reliable prognosis to single teeth
      except in the case of a clearly hopeless tooth. Therefore, it is crucial to
      gather the greatest quantity of data to determine the role that every single
      element can play in the prosthetic rehabilitation of the case. The following
      report deals with the management of a multidisciplinary periodontally compromised
      case in which a treatment strategy and chronology were designed to reach clinical
      predictability while reducing the duration of the therapy.

PMID- 27891262
TI  - Comment on "Facial Atrophy in Oral Submucous Fibrosis: An Association or a
      Coincidence".

PMID- 27891263
TI  - Coverage Root after Removing Peripheral Ossifying Fibroma: 5-Year Follow-Up Case
      Report.
AB  - When lesions in soft tissue reach the gingival margin, they can produce aesthetic
      defects during its permanence and after its removal. Periodontal plastic surgery
      allows the correction of the gingival contour using different techniques. This
      paper is a case report of a peripheral ossifying fibroma removal in the
      interproximal area of teeth 21 and 22 in addition to root coverage of the
      affected area through two surgical phases: keratinized gingival tissue
      augmentation surgery with free gingival graft concurrent with removal of the
      lesion and, in a second stage, root coverage by performing coronally advanced
      flap technique with a follow-up of five years. The initial results achieved,
      which were root coverage of 100% after 6 months, promoted an adequate gingival
      contour and prevented the development of a mucogingival defect or a root exposure
      with its functional and aesthetic consequences. After five years, the results
      showed long term success of the techniques, where the margin remained stable with
      complete root coverage and tissues were stable and harmonic in color.

PMID- 27891264
TI  - World's First Clinical Case of Gene-Activated Bone Substitute Application.
AB  - Treatment of patients with large bone defects is a complex clinical problem. We
      have initiated the first clinical study of a gene-activated bone substitute
      composed of the collagen-hydroxyapatite scaffold and plasmid DNA encoding
      vascular endothelial growth factor. The first patient with two nonunions of
      previously reconstructed mandible was enrolled into the study. Scar tissues were
      excised; bone defects (5-14 mm) between the mandibular fragments and
      nonvascularized rib-bone autograft were filled in with the gene-activated bone
      substitute. No adverse events were observed during 12 months of follow-up. In 3
      months, the average density of newly formed tissues within the implantation zone
      was 402.21 +/- 84.40 and 447.68 +/- 106.75 HU in the frontal and distal regions,
      respectively, which correlated with the density of spongy bone. Complete distal
      bone defect repair with vestibular and lingual cortical plates formation was
      observed in 6 and 12 months after surgery; thereby the posterior nonunion was
      successfully eliminated. However, there was partial resorption of the proximal
      edge of the autograft entailed to relapse of the anterior nonunion. Thus, the
      first clinical data on the safety and efficacy of the gene-activated bone
      substitute were obtained. Given a high complexity of the clinical situation the
      treatment, results might be considered as promising. NCT02293031.

PMID- 27891265
TI  - A Unique Case of Pancreatic Mass due to Pancreatic Elastofibromatosis.
AB  - Elastofibroma is a benign tumor of the musculoskeletal system characterized by
      the abnormal accumulation of elastinophilic fibers. It has been classically
      described for subscapular region but has been reported in several musculoskeletal
      sites over the years and rarely even in the GI tract but never in pancreas. We
      therefore present the case of a 45-year-old female who presented with
      intermittent abdominal pain. CT of abdomen revealed 1.4 cm pancreatic neck lesion
      without peripancreatic lymphadenopathy. Endoscopic ultrasound (EUS) guided FNA
      was nondiagnostic. Surgical resection was performed with central pancreatectomy.
      Histopathology revealed well demarcated nodules of hypocellular collagen with
      abundant elastic fibers, characteristic of pancreatic elastofibroma. Treatment is
      not needed unless symptomatic and surgical resection is the preferred therapeutic
      option when indicated. This case adds another entity to the differential
      diagnosis of pancreatic mass lesions.

PMID- 27891266
TI  - A Silent and Chronic Complication of Percutaneous Endoscopic Gastrostomy Tube:
      Small Bowel Enterocutaneous Fistula.
AB  - Percutaneous endoscopic gastrostomy (PEG) has gradually gained the popularity
      since its invention and become the most preferred method for gastrostomy
      insertion in recent years. PEG is associated with lower morbidity and mortality
      and has the advantages of being minimally invasive and more convenient over the
      conventional open gastrostomy. However, significant rates of major complication
      still occur. Enterocutaneous fistula is one of the key complications that can be
      easily neglected due to its asymptomatic nature. We present a case of small bowel
      enterocutaneous fistula which was only found 8 years after the PEG insertion,
      being diagnosed after the longest duration of delay in diagnosis reported in
      literature.

PMID- 27891267
TI  - Marginal Zone Lymphoma Complicated by Protein Losing Enteropathy.
AB  - Protein losing enteropathy (PLE) refers to excessive intestinal protein loss,
      resulting in hypoalbuminemia. Underlying pathologies include conditions leading
      to either reduced intestinal barrier or lymphatic congestion. We describe the
      case of a patient with long-lasting diffuse abdominal problems and PLE.
      Repetitive endoscopies were normal with only minimal lymphangiectasia in
      biopsies. Further evaluations revealed an indolent marginal zone lymphoma with
      minor bone marrow infiltration. Monotherapy with rituximab decreased bone marrow
      infiltration of the lymphoma but did not relieve PLE. Additional treatments with
      steroids, octreotide, a diet devoid of long-chain fatty-acids, and parenteral
      nutrition did not prevent further clinical deterioration with marked weight loss
      (23 kg), further reduction in albumin concentrations (nadir 8 g/L), and a
      pronounced drop in performance status. Finally, immunochemotherapy with rituximab
      and bendamustine resulted in hematological remission and remarkable clinical
      improvement. 18 months after therapy the patient remains free of gastrointestinal
      complaints and has regained his body weight with normal albumin levels. We
      demonstrate a case of PLE secondary to indolent marginal zone lymphoma. No
      intestinal pathologies were detected, contrasting a severe and almost lethal
      clinical course. Immunochemotherapy relieved lymphoma and PLE, suggesting that a
      high suspicion of lymphoma is warranted in otherwise unexplained cases of PLE.

PMID- 27891268
TI  - A Case Report Describing a Rare Presentation of Simultaneous Occurrence of MPO
      ANCA-Associated Vasculitis and Rheumatoid Arthritis.
AB  - Background. Renal-limited myeloperoxidase vasculitis with simultaneous rheumatoid
      arthritis is reported as a rare occurrence. Review of literature suggests that
      most patients had a diagnosis of rheumatoid arthritis for several years prior to
      presenting with renal failure from myeloperoxidase vasculitis. Case Presentation.
      A 58-year-old Caucasian male presented to the hospital experiencing malaise,
      fevers, decreased oral intake, nausea, and vomiting for one week duration. His
      past medical history consisted of newly diagnosed but untreated rheumatoid
      arthritis, hypertension, and non-insulin-dependent diabetes mellitus. He was
      found to have acute renal failure, proteinuria, and hypoglycemia. Standard
      therapy, including intravenous fluids, did not improve his acute renal failure. A
      vasculitis workup resulted in a positive myeloperoxidase anti-neutrophil
      cytoplasmic antibody (MPO-ANCA). Renal biopsy revealed crescentic
      glomerulonephritis (GN) pauci-immune type, suggestive of MPO-ANCA-associated
      vasculitis (MPO-AAV). Treatment consisted of prednisone, cyclophosphamide, and
      seven cycles of plasmapheresis, in addition to hemodialysis for uremia. Upon
      discharge, he received hemodialysis for another week and continued treatment with
      cyclophosphamide and prednisone. Conclusion. Patients with longstanding
      rheumatoid arthritis may develop renal failure due to nonsteroidal anti
      inflammatory medication use and AA type amyloidosis; however, necrotizing
      glomerulonephritis with crescent formation has been rarely reported. This
      stresses the importance of early recognition and swift initiation of treatment.

PMID- 27891269
TI  - Unruptured Basilar Tip Aneurysm with Internal Septation: Coiling Implications?
AB  - An internal septum within a basilar artery aneurysm is an infrequent anomaly and
      is very rarely reported in the literature. We report a 62-year-old lady that was
      incidentally diagnosed with basilar tip aneurysm. Further imaging with magnetic
      resonance imaging (MRI) revealed internal septation within this aneurysm which
      was later confirmed with digital subtraction angiography (DSA). She underwent
      coil embolisation, which involved technical manipulation of the microcatheter and
      the balloon to enable coiling of each separate aneurysm compartment. We present
      this case to illustrate the effect of this anatomical variation on the selection
      of endovascular treatment strategy.

PMID- 27891270
TI  - Primary Diffuse Leptomeningeal Gliomatosis: Radiological/Pathological Features.
AB  - We present the case of a 43-year-old lady who presented with headaches, visual
      impairment, and seizures, progressing rapidly over the course of a few weeks.
      Extensive workup excluded an inflammatory or infectious cause. Imaging studies
      revealed diffuse thickening of the leptomeninges and serial CSF analysis showed
      raised opening pressures and increased protein levels. A diagnostic biopsy of the
      lower thoracic dura confirmed the diagnosis of primary diffuse leptomeningeal
      gliomatosis (PDGL). She was managed supportively for her symptoms and
      unfortunately she passed away a few weeks later.

PMID- 27891271
TI  - Intrahepatic Cholestasis of Pregnancy with Severe Elevation of Bile Acids in the
      Setting of Acute Hepatitis C Infection.
AB  - Intrahepatic cholestasis of pregnancy (ICP) is a complication of pregnancy
      resulting in elevation of serum bile acid levels. ICP is often associated with
      underlying liver disease, including hepatitis C. Bile acids in relationship to
      the acute infection of hepatitis C virus have not yet been delineated in the
      literature. A 26-year-old gravida 4 para 2103 with dichorionic, diamniotic twin
      gestation and history of intravenous drug abuse developed ICP in the setting of
      acute hepatitis C infection. In addition to clinical symptoms of pruritus and
      right upper quadrant pain, she developed severe elevation in bile acids, 239
      micromol/L, and transaminitis aspartate aminotransferase 1033 U/L, and alanine
      aminotransferase 448 U/L. She received ursodeoxycholic acid and antenatal testing
      was performed. Patient delivered vaginally at 33-week gestation following preterm
      rupture of membranes. Neonates were admitted to NICU and had uncomplicated
      neonatal courses. In the setting of ICP with significant transaminitis and severe
      elevation of bile acids, consideration of acute viral hepatitis is important,
      especially considering the worsening opioid epidemic and concurrent increase in
      intravenous drug use in the United States. Further study is needed regarding the
      acute form of HCV infection and its effect on ICP and associated bile acids.

PMID- 27891272
TI  - Spontaneous Rupture of Uterine Artery in a 14-Week Pregnant Woman.
AB  - We report a case of uterine artery rupture in a woman at 14 weeks' gestation who
      presented with abdominal pain, tachycardia, and hypotension and underwent a
      diagnostic laparoscopy. During this procedure, a spontaneous rupture of the left
      uterine artery was diagnosed and the surgery was converted into a laparotomy. The
      artery was bound to its origin and to its distal uterine portion. The patient
      exhibited excellent postoperative recovery and was discharged two days after the
      surgery. The pregnancy continued without other maternal or fetal complications,
      and the patient delivered a healthy newborn via cesarean section at 39 weeks of
      gestation.

PMID- 27891273
TI  - Orbital Infarction due to Sickle Cell Disease without Orbital Pain.
AB  - Sickle cell disease is a hemoglobinopathy that results in paroxysmal arteriolar
      occlusion and tissue infarction that can manifest in a plurality of tissues.
      Rarely, these infarcted crises manifest in the bony orbit. Orbital infarction
      usually presents with acute onset of periorbital tenderness, swelling, erythema,
      and pain. Soft tissue swelling can result in proptosis and attenuation of
      extraocular movements. Expedient diagnosis of sickle cell orbital infarction is
      crucial because this is a potentially sight-threatening entity. Diagnosis can be
      delayed since the presentation has physical and radiographic findings mimicking
      various infectious and traumatic processes. We describe a patient who presented
      with sickle cell orbital crisis without pain. This case highlights the importance
      of maintaining a high index of suspicion in patients with known sickle cell
      disease or of African descent born outside the United States in a region where
      screening for hemoglobinopathy is not routine, even when the presentation is not
      classic.

PMID- 27891274
TI  - A Rare Case of Lateral Canthal Gouty Tophus Presenting as an Eyelid Mass.
AB  - A 41-year-old man with a history of gout presented with an enlarging eyelid
      growth. Clinical examination revealed a mildly indurated nodule at the lateral
      canthus. Following resection, histopathological examination revealed needle
      shaped, crystalline material surrounded by multinucleated giant cells, findings
      consistent with gouty tophus. This represents just the sixth case of gouty tophus
      of the eyelid reported in the literature.

PMID- 27891275
TI  - Tortuous Carotid Artery Extended to Neck Level IIb Mimicking the Metastatic Mass.
AB  - Specifically in neck level IIb, the expected normal anatomy does not contain any
      vital structures and consequently it might direct a surgeon to perform rapid
      surgical dissection of tissues. Therefore aberrant anatomy of the vessels in the
      patients may be overlooked during neck dissection. Unexpected and potentially
      devastating injuries can be avoided by respecting the possible aberrant anatomy
      in any level of the neck. In this case report, a 74-year-old man was presented
      with laryngeal carcinoma who was treated with laryngectomy and bilateral neck
      dissection. During the left side neck dissection, tortuous internal carotid
      artery imitating a metastatic mass was unexpectedly encountered in level IIb. As
      in this case, surgeons should keep in mind possible aberrant anatomy during the
      neck dissection and perform surgery staying in surgical principles to be safe for
      an unforeseen and potential dangerous injuries.

PMID- 27891276
TI  - Blue Ear Cyst: A Rare Eccrine Hidrocystoma of the Ear Canal and Successful
      Endoscopic Excision.
AB  - Aims. Hidrocystomas are benign cystic growths of the apocrine and eccrine sweat
      glands. These cystic lesions have been well documented on the face, head, and
      neck, but rarely in the external auditory canal. Presentation of Case. A 67-year
      old woman presented with a bluish cystic mass partially occluding the external
      auditory canal and interfering with hearing aid use. Lesion was excised
      completely via a transcanal endoscopic approach with excellent cosmetic results,
      no canal stenosis, and no recurrence at 1-year follow-up. Discussion. We present
      a rare eccrine hidrocystoma of the external auditory canal and successful
      excision of this benign lesion. We describe the surgical management using a
      transcanal endoscopic approach and follow-up results. An eccrine gland cyst that
      presents as a mass occluding the external auditory canal is quite rare. There are
      only a few such cases reported in the literature. These masses can be mistaken
      for basal cell carcinomas or cholesterol granulomas but can be easily
      differentiated using histopathology. Conclusion. Eccrine hidrocystoma is a cystic
      lesion of sweat glands, rarely found in the external auditory canal. A
      characteristic bluish hue aids in diagnosis and surgical excision using ear
      endoscopy provides excellent control.

PMID- 27891277
TI  - A Case of Ameloblastic Fibroodontoma Extending Maxillary Sinus with Erupted
      Tooth: Is Transcanine Approach with Alveolectomy Feasible?
AB  - Ameloblastic fibroodontoma (AFO) is a rare entity of mixed odontogenic tumors and
      frequently arises from posterior portion of the maxilla or mandible in first two
      decades of life. Herein, a 35-year-old woman with a noncontributory medical
      history who presented with a progressive left maxillary toothache, left maxillary
      first molar tooth mobility, and swelling in the left maxillary molar area for the
      last 2 months was reported. Radiologically, a tumor that originated from
      periapical area of the second mature molar teeth of maxilla was seen and
      additively unerupted tooth was not detected. The histopathologic examination
      revealed AFO. The patient is disease-free for five years after treated with
      limited segmental alveolectomy combining with Caldwell-Luc procedure.

PMID- 27891278
TI  - Becker's Nevus Syndrome in a Pediatric Female Patient.
AB  - Becker's nevus syndrome is part of the epidermal nevus syndromes and has been
      described with a phenotype that includes Becker's nevus, ipsilateral breast
      hypoplasia, and variable skeletal malformations. It is more frequent in males
      than in females (5 : 1) but is more relevant in females. The diagnosis is
      clinically based and the skin lesion must be present and no other numbered
      criteria have been established, but with more criteria being present the
      possibility of the diagnosis is higher. Regarding the treatment of breast
      hypoplasia, the use of antiandrogen medication has demonstrated adequate clinical
      response in a dose of 50 mg/day of spironolactone.

PMID- 27891279
TI  - Multiple Gastric Erosion Early after a 3 V Lithium Battery (CR2025) Ingestion in
      an 18-Month-Old Male Patient: Consideration about the Proper Time of
      Intervention.
AB  - Introduction. Button battery ingestion is considered an emergency situation in
      pediatric patients that needs to be managed promptly; otherwise, it may lead to
      serious and potentially lethal complications, especially when it is impacted in
      the esophagus. Less attention has been given in cases where the battery passes
      into the stomach, with guidelines for emergency intervention being based on the
      presence of symptoms. Case Report. We present a case of an 18-month-old male
      patient who presented to our emergency department after button battery ingestion.
      He did not have any symptoms and no pathological findings were encountered during
      clinical examination. X-ray investigation revealed the presence of the battery in
      the stomach. The patient was admitted for observation and two hours later he had
      two episodes of vomiting. He underwent urgent endoscopic removal of the battery
      where multiple acute gastric mucosal erosion in place of direct contact of the
      battery's negative pole with the mucosa of the gastric antrum was found.
      Conclusion. In specific cases the urgent endoscopic intervention for removal of
      an ingested button battery that is located in the stomach even in asymptomatic
      patients should be suggested.

PMID- 27891280
TI  - Lung Ultrasound in Early Diagnosis of Neonatal Ventilator Associated Pneumonia
      before Any Radiographic or Laboratory Changes.
AB  - Neonatal pneumonia is reported to be the primary cause of neonatal respiratory
      failure and one of the common causes of neonatal hospitalization and death in
      developing countries. Chest X-ray was considered the gold standard for diagnosis
      of neonatal pneumonia. Lung ultrasonography has been described as a valuable
      noninvasive tool for the diagnosis of many neonatal pulmonary diseases. We report
      a case of ventilation associated neonatal pneumonia with very early diagnosis
      using lung ultrasound before any significant radiographic changes in chest X-ray
      or laboratory findings suggestive of infection.

PMID- 27891281
TI  - Septooptic Dysplasia with an Associated Arachnoid Cyst.
AB  - A 4-week-old male infant presented with hypothermia, hypoglycemia, and
      hyperbilirubinemia. His medical history was remarkable for hydrocephalus
      secondary to an arachnoid cyst, intermittent hypoglycemia, hypothermia, and poor
      feeding requiring nasogastric tube for nutrition. Physical exam revealed
      retrognathia, mild hypotonia, micropenis, and clinodactyly. Ophthalmologic exam
      demonstrated bilateral optic nerve hypoplasia (ONH). Laboratory data confirmed
      inadequate cortisol and growth hormone response to hypoglycemia, a low thyroxine
      level, and direct hyperbilirubinemia. Magnetic resonance imaging of the brain
      confirmed the known history of arachnoid cyst with hydrocephalus but also
      revealed anterior pituitary hypoplasia, absence of the posterior pituitary bright
      spot, a thin pituitary stalk, and bilateral optic nerve hypoplasia. A diagnosis
      of septooptic dysplasia (SOD) was made. Hormone replacement with hydrocortisone
      and levothyroxine was started with improvement in the infant's glycemic control,
      thermoregulation, feeding, and cholestasis. This case reinforces the importance
      of careful physical examination and laboratory review in a patient with known
      history of arachnoid cyst which has been previously described as an associated
      feature of optic nerve hypoplasia and hypopituitarism.

PMID- 27891282
TI  - A Teenage Girl with Acute Dyspnea and Hypoxemia during Red Blood Cell
      Transfusion.
AB  - Transfusion-related acute lung injury (TRALI) can cause morbidity and mortality.
      We present the case of teenager who developed dyspnea and hypoxemia few hours
      after red cell transfusion. After being admitted for close monitoring and oxygen
      therapy, her symptoms spontaneously resolved. Message: dyspnea during red cell
      transfusion should raise the suspicion of TRALI.

PMID- 27891283
TI  - Streptococcus intermedius Causing Necrotizing Pneumonia in an Immune Competent
      Female: A Case Report and Literature Review.
AB  - We report a case of a 52-year-old immunocompetent Caucasian female treated for
      necrotizing Streptococcus intermedius pneumonia and review available literature
      of similar cases. Our patient presented with respiratory failure and required
      hospitalization and treatment in the intensive care unit. Moreover, she required
      surgical drainage of right lung empyema as well as decortication and resection.
      The review of literature revealed three cases of S. intermedius pneumonia, one of
      which was a mortality. Comparison of the published cases showed a highly varied
      prehospital course and radiological presentations, with a symptomatic phase
      ranging from 10 days to five months. Radiological findings varied from an
      isolated pleural effusion to systemic disease with the presence of brain
      abscesses. Immunocompetence appears to correlate well with the overall prognosis.
      In addition, smoking appears to be an important risk factor for S. intermedius
      pneumonia. In 2 (50%) of cases, pleural fluid analysis identified S. intermedius.
      In contrast, no organism was found in our patient, necessitating the acquisition
      of lung tissue sample for the diagnosis. In conclusion, both medical and surgical
      management are necessary for effective treatment of S. intermedius pneumonia. The
      outcome of treatment is good in immunocompetent individuals.

PMID- 27891284
TI  - Strangulated Morgagni's Hernia: A Rare Diagnosis and Management.
AB  - Morgagni hernia is a rare type of congenital diaphragmatic hernia. It accounts
      for only 3% of all diaphragmatic hernias. The defect is small and hernia being
      asymptomatic in the majority presents late in adulthood. Obstruction or
      incarceration in Morgagni hernia is uncommon. We report a rare occurrence of
      strangulated Morgagni hernia. A 40-year-old gentleman presented to our emergency
      department with features of intestinal obstruction. Computed tomography of the
      chest and abdomen showed a strangulated right Morgagni hernia. An exploratory
      laparotomy was performed with resection of the ischemic bowel segment with
      anastomosis and a primary repair of the diaphragmatic defect. Postoperative
      recovery was uneventful and asymptomatic at follow-up.

PMID- 27891285
TI  - Complex Perineal Trauma with Anorectal Avulsion.
AB  - Introduction. The objective of this case report is to illustrate a severe
      perineal impalement injury, associated with anorectal avulsion and hemorrhagic
      shock. Results. A 32-year-old male patient was referred to our hospital for an
      impalement perineal trauma, associated with complex pelvic fracture and massive
      perineal soft tissue destruction and anorectal avulsion. On arrival, the systolic
      blood pressure was 85 mm Hg and the hemoglobin was 7.1 g/dL. The patient was
      transported to the operating room, and perineal lavage, hemostasis, and repacking
      were performed. After 12 hours in the Intensive Care Unit, the abdominal
      ultrasonography revealed free peritoneal fluid. We decided emergency laparotomy,
      and massive hemoperitoneum due to intraperitoneal rupture of pelvic hematoma was
      confirmed. Pelvic packing controlled the ongoing diffuse bleeding. After 48
      hours, the relaparotomy with packs removal and loop sigmoid colostomy was
      performed. The postoperative course was progressive favorable, with discharge
      after 70 days and colostomy closure after four months, with no long-term
      complications. Conclusions. Severe perineal injuries are associated with
      significant morbidity and mortality. Their management in high volume centers,
      with experience in colorectal and trauma surgery, allocating significant human
      and material resources, decreases the early mortality and long-term
      complications, offering the best quality of life for patients.

PMID- 27891286
TI  - Spontaneous Intramural Duodenal Hematoma: Pancreatitis, Obstructive Jaundice, and
      Upper Intestinal Obstruction.
AB  - Nontraumatic intramural duodenal hematoma can cause upper gastrointestinal tract
      obstruction, upper gastrointestinal hemorrhage, jaundice, and pancreatitis and
      may be present in patients with normal coagulation. However the pathogenesis of
      the condition and its relationship with acute pancreatitis remain unknown. We
      present a case of spontaneous intramural duodenal hematoma and a case of
      successful nonoperative treatments.

PMID- 27891287
TI  - Sapovirus Gastroenteritis in Young Children Presenting as Distal Small Bowel
      Obstruction: A Report of 2 Cases and Literature Review.
AB  - Abdominal pain and distention in children are commonly encountered problems in
      the pediatric emergency room. The majority of complaints are found to be due to
      benign entities such as gastroenteritis and constipation. What confounds these
      diagnoses is that young children often deliver a challenging and unreliable exam.
      Thus, it often becomes exceedingly problematic to differentiate these benign
      conditions from surgical conditions requiring prompt attention including small or
      large bowel obstruction, volvulus, and appendicitis. The cases highlight
      Sapovirus as a cause of severe abdominal distention and vomiting in children and
      this report is the first to describe and demonstrate the impressive radiologic
      findings that may be associated with this infection. Surgeons should heed this
      information and hesitate to emergently operate on similar children.

PMID- 27891288
TI  - Massive Ascites in a Renal Transplant Patient after Laparoscopic Fenestration of
      a Lymphocele.
AB  - Retroperitoneal lymphocele is a common complication of renal transplantation.
      Here, we report the case of a 67-year-old woman with massive ascites after
      fenestration surgery for a lymphocele that developed following renal
      transplantation. She had been on continuous ambulatory peritoneal dialysis for 9
      years. Living donor renal transplantation was performed and an intrapelvic
      lymphocele subsequently developed. The lymphocele did not resolve after
      aspiration therapy; therefore, laparoscopic fenestration was performed. Although
      the lymphocele disappeared, massive ascites appeared in its stead. Half a year
      later, the ascites was surgically punctured, which then gradually resolved and
      disappeared 6 weeks later. Aspiration therapy should be considered in patients on
      long-term peritoneal dialysis, although laparoscopic fenestration is safe and
      effective.

PMID- 27891290
TI  - A Comparative Study of Assay Performance of Commercial Hepatitis E Virus Enzyme
      Linked Immunosorbent Assay Kits in Australian Blood Donor Samples.
AB  - Hepatitis E virus (HEV) is transfusion-transmissible and therefore poses a risk
      to blood transfusion safety. Seroprevalence studies are useful for estimating
      disease burden and determining risk factors. Considerable variability in the
      sensitivity of HEV antibody detection assays exists. This study aimed to compare
      the performances of commercially available HEV enzyme-linked immunosorbent assays
      (ELISA) in Australian blood donor samples. Plasma samples that tested positive (n
      = 194) or negative (n = 200) for HEV IgG (Wantai HEV IgG ELISA) were selected. Of
      the 194 HEV IgG positive samples, 4 were positive for HEV IgM (Wantai HEV IgM
      ELISA). All samples were tested with the MP Diagnostics: HEV IgG ELISA, total
      (IgG, IgM, and IgA) HEV antibody ELISA, and HEV IgM ELISA. Of the 194 Wantai HEV
      IgG positive samples, 92 (47%) tested positive with the MP Diagnostics HEV IgG
      ELISA (kappa = 0.47) and 126 (65%) with MP Diagnostics total HEV antibody assay
      (kappa = 0.65). There was poor agreement between Wantai and MP Diagnostics HEV
      IgM assays. This study demonstrated poor agreement between the assays tested.
      These observations are consistent with previous reports demonstrating significant
      variability between HEV ELISAs, highlighting that results of HEV serology should
      be interpreted with caution.

PMID- 27891289
TI  - nor-BNI Antagonism of Kappa Opioid Agonist-Induced Reinstatement of Ethanol
      Seeking Behavior.
AB  - Recent work suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system
      may be a key mediator in the behavioral effects of alcohol. The objective of the
      present study was to examine the ability of the KOR antagonist norbinaltorphimine
      (nor-BNI) to attenuate relapse to ethanol seeking due to priming injections of
      the KOR agonist U50,488 at time points consistent with KOR selectivity. Male
      Wistar rats were trained to self-administer a 10% ethanol solution, and then
      responding was extinguished. Following extinction, rats were injected with
      U50,488 (0.1-10 mg/kg, i.p.) or saline and were tested for the reinstatement of
      ethanol seeking. Next, the ability of the nonselective opioid receptor antagonist
      naltrexone (0 or 3.0 mg/kg, s.c.) and nor-BNI (0 or 20.0 mg/kg, i.p.) to block
      U50,488-induced reinstatement was examined. Priming injections U50,488 reinstated
      responding on the previously ethanol-associated lever. Pretreatment with
      naltrexone reduced the reinstatement of ethanol-seeking behavior. nor-BNI also
      attenuated KOR agonist-induced reinstatement, but to a lesser extent than
      naltrexone, when injected 24 hours prior to injections of U50,488, a time point
      that is consistent with KOR selectivity. While these results suggest that
      activation of KORs is a key mechanism in the regulation of ethanol-seeking
      behavior, U50,488-induced reinstatement may not be fully selective for KORs.

PMID- 27891291
TI  - Knowledge about HIV in a Community Sample of Urban African Americans in the
      South.
AB  - PURPOSE: Race and HIV are intertwined in complex ways. African Americans,
      particularly those residing in the southern United States, are at great risk for
      contracting and subsequently transmitting HIV. Research on the extent to which
      members of this population understand the risks associated with engaging in
      specific behaviors is limited. This paper examines HIV knowledge among at-risk
      adult African American men and women and the factors associated with levels of
      HIV knowledge. METHODS: Based on a conceptual model derived from Social
      Disorganization Theory and Syndemics Theory, interviews were conducted between
      2009 and 2011. Questionnaire-based interviews were conducted with 1,864
      respondents from 80 strategically-chosen census block groups in Atlanta, Georgia.
      An innovative approach to assessing amount of HIV knowledge was implemented, to
      derive better estimates of the extent of knowledge. RESULTS: Overall, HIV
      knowledge was low (average=43.5% correct answers). Seven factors were identified
      as contributing uniquely to having higher levels of knowledge about HIV
      transmission: (1) younger age, (2) being educated beyond the high school level,
      (3) being gay, lesbian or bisexual, (4) experiencing sexual abuse during
      childhood and/or adolescence, (5) drinking alcohol less frequently, (6) knowing a
      larger number of HIV-infected persons and (7) knowing anyone currently living
      with "full blown" AIDS. CONCLUSION: HIV educational and intervention programs
      targeting at-risk African American adults need to develop effective ways of
      bolstering a solid understanding of how HIV is/not transmitted. In particular,
      efforts need to be targeted toward older adults, those with lower levels of
      educational attainment and persons who are not acquainted with anyone who is HIV
      infected.

PMID- 27891293
TI  - High-kVp Assisted Metal Artifact Reduction for X-ray Computed Tomography.
AB  - In X-ray computed tomography (CT), the presence of metallic parts in patients
      causes serious artifacts and degrades image quality. Many algorithms were
      published for metal artifact reduction (MAR) over the past decades with various
      degrees of success but without a perfect solution. Some MAR algorithms are based
      on the assumption that metal artifacts are due only to strong beam hardening and
      may fail in the case of serious photon starvation. Iterative methods handle
      photon starvation by discarding or underweighting corrupted data, but the results
      are not always stable and they come with high computational cost. In this paper,
      we propose a high-kVp-assisted CT scan mode combining a standard CT scan with a
      few projection views at a high-kVp value to obtain critical projection
      information near the metal parts. This method only requires minor hardware
      modifications on a modern CT scanner. Two MAR algorithms are proposed: dual
      energy normalized MAR (DNMAR) and high-energy embedded MAR (HEMAR), aiming at
      situations without and with photon starvation respectively. Simulation results
      obtained with the CT simulator CatSim demonstrate that the proposed DNMAR and
      HEMAR methods can eliminate metal artifacts effectively.

PMID- 27891292
TI  - Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance.
AB  - Cancer handles an estimated 7.6 million deaths worldwide per annum. A recent
      theory focuses on the role Cancer Stem Cells (CSCs) in driving tumorigenesis and
      disease progression. This theory hypothesizes that a population of the tumor cell
      with similar functional and phenotypic characteristics as normal tissue stem
      cells are responsible for formation and advancement of many human cancers. The
      CSCs subpopulation can differentiate into non-CSC tumor cells and promote
      phenotypic and functional heterogeneity within the tumor. The presence of CSCs
      has been reported in a number of human cancers including blood, breast, brain,
      colon, lung, pancreas prostate and liver. Although the origin of CSCs remains a
      mystery, recent reports suggest that the phenotypic characteristics of CSCs may
      be plastic and are influenced by the microenvironment specific for the individual
      tumor. Such factors unique to each tumor preserve the dynamic balance between
      CSCs to non-CSCs cell fate, as well as maintain the proper equilibrium.
      Alternating such equilibrium via dedifferentiation can result in aggressiveness,
      as CSCs are considered to be more resistant to the conventional cancer treatments
      of chemotherapy and radiation. Understanding how the tumoral microenvironment
      affects the plasticity driven CSC niche will be critical for developing a more
      effective treatment for cancer by eliminating its aggressive and recurring nature
      that now is believed to be perpetuated by CSCs.

PMID- 27891294
TI  - Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and
      Japan: facts and numbers update 2016.
AB  - Cachexia is a serious clinical consequence of almost all chronic diseases when
      reaching advanced stages. Its prevalence ranges from 5-15% in end-stage chronic
      heart failure to 50-80% in advanced malignant cancer. Cachexia is also frequently
      occurring in patients with chronic kidney disease, chronic obstructive pulmonary
      disease (COPD) or neurological diseases, and rheumatoid arthritis. Mortality
      rates of patients with cachexia range from 15-25% per year in severe COPD through
      20-40% per year in patients with chronic heart failure or chronic kidney disease
      to 20-80% in cancer cachexia. In the industrialized world (North America, Europe,
      and Japan) where epidemiological data are to some degree available, the overall
      prevalence of cachexia (due to any disease and not necessarily associated with
      hospital admission) is growing with the growth of the chronic illness prevalence,
      and it currently affects around 0.5-1.0% of the population, i.e. around 6-12
      million people. From this, one can estimate that 1.5-2 million deaths are
      occurring in patients with cachexia per year. It is also a very significant
      health problem in other parts of the globe, but epidemiological data are scarce.
      The multifactorial nature of cachexia is now much better understood, and
      particularly, the role of inflammatory mediators and the imbalance of anabolism
      and catabolism are considered important therapeutic targets. Several approaches
      to develop cachexia and muscle wasting treatments have failed to be successful in
      phase III clinical trials, but new approaches are in development. Given the high
      prevalence and very high mortality associated with cachexia, advances are
      urgently needed for patients worldwide.

PMID- 27891295
TI  - Cachexia: looking yet not seeing.

PMID- 27891296
TI  - Welcome to the ICD-10 code for sarcopenia.
AB  - The new ICD-10-CM (M62.84) code for sarcopenia represents a major step forward in
      recognizing sarcopenia as a disease. This should lead to an increase in
      availability of diagnostic tools and the enthusiasm for pharmacological companies
      to develop drugs for sarcopenia.

PMID- 27891297
TI  - Exercise rehabilitation following intensive care unit discharge for recovery from
      critical illness: executive summary of a Cochrane Collaboration systematic
      review.
AB  - Skeletal muscle wasting and weakness are major complications of critical illness
      and underlie the profound physical and functional impairments experienced by
      survivors after discharge from the intensive care unit (ICU). Exercise-based
      rehabilitation has been shown to be beneficial when delivered during ICU
      admission. This review aimed to determine the effectiveness of exercise
      rehabilitation initiated after ICU discharge on primary outcomes of functional
      exercise capacity and health-related quality of life. We sought randomized
      controlled trials, quasi-randomized controlled trials, and controlled clinical
      trials comparing an exercise intervention commenced after ICU discharge vs. any
      other intervention or a control or 'usual care' programme in adult survivors of
      critical illness. Cochrane Central Register of Controlled Trials, Medical
      Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica
      Database, and Cumulative Index to Nursing and Allied Health Literature databases
      were searched up to February 2015. Dual, independent screening of results, data
      extraction, and quality appraisal were performed. We included six trials
      involving 483 patients. Overall quality of evidence for both outcomes was very
      low. All studies evaluated functional exercise capacity, with three reporting
      positive effects in favour of the intervention. Only two studies evaluated health
      related quality of life and neither reported differences between intervention and
      control groups. Meta-analyses of data were precluded due to variation in study
      design, types of interventions, and selection and reporting of outcome
      measurements. We were unable to determine an overall effect on functional
      exercise capacity or health-related quality of life of interventions initiated
      after ICU discharge for survivors of critical illness. Findings from ongoing
      studies are awaited. Future studies need to address methodological aspects of
      study design and conduct to enhance rigour, quality, and synthesis.

PMID- 27891298
TI  - Pt-Decorated g-C3N4/TiO2 Nanotube Arrays with Enhanced Visible-Light
      Photocatalytic Activity for H2 Evolution.
AB  - Aligned TiO2 nanotube layers (TiNTs) grown by self-organizing anodization of a Ti
      substrate in a fluoride-based electrolyte were decorated with graphitic-phase
      C3N4 (g-C3N4) via a facile chemical vapor deposition approach. In comparison with
      classical TiO2 nanotubes (anatase), the g-C3N4/TiNTs show an onset of the
      photocurrent at 2.4 eV (vs. 3.2 eV for anatase) with a considerably high
      photocurrent magnitude in the visible range. After further decoration with Pt
      nanoparticles, we obtained a visible-light responsive platform that showed,
      compared with g-C3N4-free TiNTs, a strong enhancement for photoelectrochemical
      and bias-free H2 evolution (15.62 MULh-1 cm-2), which was almost a 98-fold
      increase in the H2 production rate of TiNTs (0.16 MULh-1 cm-2). In a wider
      context, the g-C3N4-combined 3 D nanoporous/nanotubular structure thus provides a
      platform with significant visible-light response in photocatalytic applications.

PMID- 27891299
TI  - Tourette Syndrome and Comorbid Neuropsychiatric Conditions.
AB  - Tourette syndrome is a neuropsychiatric condition characterized by both motor and
      phonic tics over a period of at least 1 year with the onset in childhood or
      adolescence. Apart from the tics, most of the patients with Tourette syndrome
      have associated neuropsychiatric comorbidities consisting of attention deficit
      hyperactivity disorder, obsessive compulsive disorder, rage attacks, sleep
      issues, depression, and migraine. Patients may also have physical complications
      directly from violent motor tics which can rarely include cervical myelopathy,
      arterial dissection, and stroke. The purpose of this article is to review the
      associated neuropsychiatric comorbidities of Tourette syndrome with emphasis on
      recent research.

PMID- 27891300
TI  - Fetal Alcohol Spectrum Disorders (FASD): an Approach to Effective Prevention.
AB  - PURPOSE OF REVIEW: The objective of the current contribution is to propose an
      evidence-based, six-step approach to develop effective programs for prevention of
      fetal alcohol spectrum disorders. RECENT FINDINGS: Despite widespread campaigns
      aimed to reduce prenatal alcohol exposure, the number of affected children
      continues to be high. Current strategies to reduce prenatal alcohol exposure may
      be ineffective or counterproductive. However, proven principles of health
      promotion could be applied to reduce drinking in pregnancy. One such approach is
      Intervention Mapping (IM), a six-step procedure based on proven principles to
      change behaviors. SUMMARY: FASD affects all communities and is an underestimated
      problem worldwide. Programs based on proven principles of behavior change are
      warranted. Program developers can use pre-existing protocols and strategies from
      evidence-based practice, such as Intervention Mapping. Developers who plan their
      preventive programs in a systematic and evidence-based manner increase the
      chances of success in reducing prenatal alcohol exposure and FASD.

PMID- 27891301
TI  - How Far Have We Come in the Field of Nerve Regeneration After Trigeminal Nerve
      Injury?
AB  - Patients suffering from nerve injury with sensory disturbances or orofacial pain
      have greatly reduced quality of life, and it is a big cost for the society.
      Abnormal sensations caused by trigeminal nerve injury often become chronic,
      severely debilitating, and extremely difficult to treat. In general, non-invasive
      treatment such as drug treatment has been insufficient, and there are currently
      few available effective treatments. Surgical interventions such as end-to-end
      connection or nerve grafting have disadvantages such as donor site morbidity or
      formation of neuroma. There is need for optimizing the technique for nerve
      repair, especially for the trigeminal nerve system, which has so far not yet been
      well explored. Recently, tissue engineering using biodegradable synthetic
      material and cell-based therapies represents a promising approach to nerve repair
      and it has been reported that mesenchymal stem cell (MSC) has an anti
      inflammatory effect and seems to play an important role in nerve healing and
      regeneration.

PMID- 27891303
TI  - Constructing public health policies in post crisis countries: lessons to learn
      from the associations between free-sugars consumption and diabetes, obesity and
      dental caries before, during and after sanctions in Iraq.
AB  - BACKGROUND: This article aims to provide evidence for an informed public health
      policy on free-sugar consumption in post-crisis countries. METHODS: Iraq was
      selected as a case study. A systematic search for published data on the
      prevalence/incidence of type-2 diabetes, overweight/obesity, dental caries and
      free-sugar consumption levels in Iraq was conducted using MEDLINE, the Iraqi
      Academic Scientific journals and relevant international organisations' websites.
      Comparable data before (1980-1990), during (1991-2002) and after (2003-2015) the
      United Nations sanctions (UNS) were included. RESULTS: Ten studies were included.
      Quality scores ranged between 3 and 7/8. Free-sugar consumption decreased
      dramatically during the UNS (from 50 to 16.3 kg/person/year) and started
      increasing afterwards (24.1 kg/person/year). Changes in type-2 diabetes,
      overweight/obesity and caries levels mirrored those of free-sugar consumption.
      Caries declined markedly during UNS and started increasing afterwards. Comparable
      data on diabetes and overweight/obesity were only available for the periods
      during and after the UNS. Both of these conditions started increasing with
      increased free-sugar consumption after lifting the UNS. CONCLUSIONS: There is a
      need to develop a public health policy in post-crisis countries to maintain the
      reduction in free-sugar consumption, and hence promote both general and dental
      health, by integrating the common risk factor approach into the social
      determinant framework.

PMID- 27891302
TI  - Epidemiology of Sjogren's Syndrome-from an Oral Perspective.
AB  - Oral symptoms are among the most distressing manifestations for patients with
      Sjogren's syndrome (SS). The feeling of dry mouth is unpleasant, and
      hyposalivation may contribute to difficulty in speaking, chewing and swallowing
      and reduced quality of life. Reduced salivary flow increases the risk for dental
      caries and problems with prosthetic replacement. It seems that SS is not as
      frequently occurring as previously anticipated. Population-based prevalence
      studies on primary SS in Europe, conducted on large background populations and in
      accordance with the AECG criteria, reported of a prevalence of 1-9 cases per
      10,000 people. This gives a combined prevalence of nearly 39/100,000 (~0.04 %).
      The cause of Sjogren's syndrome is even now not fully understood, and the
      treatment of oral symptoms is still mostly palliative. Hopefully, useful
      information will appear from the new methods that are now available for genome
      wide association studies, epigenetics, DNA methylation studies, and proteomics.
      Similarly, this is anticipated for the immunological side of the story. The
      interferon signature, the interferon gamma/interferon alpha mRNA ratio, and
      CXCL13 are among the proposed biomarkers of active disease. In this review, we
      provide an update on oral aspects of Sjogren's syndrome with emphasis on the
      latest publications on these topics.

PMID- 27891305
TI  - Single file reciprocating systems: A systematic review and meta-analysis of the
      literature: Comparison of reciproc and WaveOne.
AB  - The introduction of single-file nickel-titanium (NiTi) reciprocating systems has
      been a major breakthrough in the field of endodontics. Thus, the aim of this
      study was to compare the available reciprocating systems, Reciproc and WaveOne,
      using a meta-analysis with different parameters. A comprehensive electronic
      literature search for Reciproc and WaveOne using PubMed and Google scholar was
      initially conducted in September 2014 and updated in September 2016. Inclusion
      and exclusion criteria were then established. Twenty-six studies were qualified
      for the systematic review, and only three studies were considered for the meta
      analysis using cyclic fatigue resistance as the main parameter. The time to
      fracture for the Reciproc and WaveOne systems ranged from 119.7 sec to 156.4 sec
      and 74.8 sec to 99.6 sec, respectively. The pooled difference in mean time to
      fracture was longer for the Reciproc system by 45.6 sec. This difference was
      statistically significantly at P value < 0.001. In conclusion, our study supports
      the finding that Reciproc is more resistant to cyclic fatigue than WaveOne.
      However, with regard to other parameters, mixed results were obtained. Well
      designed randomized clinical trials comparing both systems under the same
      experimental conditions should be done in future studies.

PMID- 27891306
TI  - Forces in initial archwires during leveling and aligning: An in-vitro study.
AB  - AIM: This in-vitro study measured the force deflection behavior of selected
      initial alignment archwires by conducting three-point bending tests under
      controlled tests. The study tested three wire designs, namely, co-axial
      multistranded stainless steel wires, nickel-titanium, and copper-nickel-titanium
      archwires. MATERIALS AND METHODS: The archwires were ligated to a specially
      designed metal jig, simulating the arch. A testing machine (Instron) recorded
      activation and deactivation forces of different deflections at 37 degrees C.
      Forces on activation and deactivation were compared by one-way analysis of
      variance (ANOVA). RESULTS: Significant differences (P < 0.05) in activation and
      deactivation forces were observed among the tested wires. The co-axial
      multistranded wire had the lowest mean activation and deactivation forces,
      whereas conventional nickel-titanium wires had more mean activation and
      deactivation forces at different deflections. CONCLUSION: The activation and
      deactivation forces were higher for nickel-titanium followed by copper-nickel
      titanium and co-axial wires. The amount of percentage force loss was more for co
      axial wire, indicating that these wires are not ideal for initial leveling and
      aligning.

PMID- 27891307
TI  - Morphological analysis of palatal rugae pattern in central Indian population.
AB  - AIM: The aim of this study was to analyze the morphological study of palatal
      rugae pattern in a central Indian population and to determine sex
      differentiation. OBJECTIVES: To investigate the distinctive rugae patterns of the
      study population and determine the contribution of rugae patterns in gender
      identification. MATERIAL AND METHODS: The present cross-sectional study was
      conducted among a Central Indian population with a sample size of 500
      participants. The study involved 250 males and 250 females who were randomly
      selected from the outpatient department of Oral Medicine Diagnosis and Radiology,
      Hitkarini Dental College and Hospital, Jabalpur, Madhya Pradesh. After collection
      of impression, casts were made and analyzed to evaluate the palatal rugae pattern
      in a central Indian population by using Thomas and Kotze classification (1983)
      for number, shape, direction, and unification of palatal rugae pattern. The
      statistical analysis was carried out using Mann-Whitney test and Chi-square
      (chi2) tests for categorical variables. RESULT: Males showed more number of rugae
      than females [P = 0.00 (<=0.001)]. Males had more number of wavy rugae pattern
      whereas females showed more number of straight rugae patterns [P = 0.00
      (<=0.001)]. Males showed more backwardly directed rugae whereas females showed
      more forwardly directed rugae [P = 0.00 (<=0.001)]. The unification did not show
      any significant difference. CONCLUSION: This study showed that there was a
      significant relationship between palatoscopy, human identification, and sex
      determination. Thus, palatoscopy can be considered as a cost effective, easy,
      unique, and stable method for human identification.

PMID- 27891304
TI  - Metastasis to the oral soft tissues: A review of 412 cases.
AB  - The present review article analyzes the characteristics of metastases to the oral
      soft tissues from 1937 to 2015. An extensive literature search was performed. All
      variables such as age, gender, and primary and secondary tumor sites were
      analyzed. Metastases to the major salivary glands were not included in this
      review. In general, there were 412 metastatic lesions developed in the oral soft
      tissues. The male-to-female ratio was approximately 1.8:1. The mean age of the
      patients at diagnosis was 58. The lung was the most common primary site and the
      gingiva was the most common metastatic site. The greater part of the histological
      examination yielded adenocarcinoma. The diagnosis of a metastatic lesion in the
      oral cavity is a challenge to the clinicians due to the lack of pathognomonic
      signs and symptoms. Oral metastases usually occur in the advanced stages of
      cancers, and the interval between appearance and death is usually short. The oral
      soft tissue metastasis can be easily recognized compared to the metastasis of
      jawbones. Early detection of oral lesions is important in the case of being the
      first sign of a malignancy in other parts of body.

PMID- 27891308
TI  - Comparative evaluation of the efficacy of fluoride varnish and casein
      phosphopeptide - Amorphous calcium phosphate in reducing Streptococcus mutans
      counts in dental plaque of children: An in vivo study.
AB  - AIM: To assess the comparative efficacy of fluoride varnish and casein
      phosphopeptide-amorphous calcium phosphate (CPP-ACP) complex visa viz.
      Streptococcus mutans in plaque, and thereby the role that these two agents could
      play in the prevention of dental caries. MATERIALS AND METHODS: A cluster sample
      of 120 caries inactive individuals belonging to moderate and high caries risk
      group were selected from 3-5-year-old age group based on the criteria given by
      Krassee and were randomized to four groups, namely, fluoride varnish - Group I,
      CPP-ACP complex - Group II, mixture of CPP-ACP complex -Gourp III, and fluoride
      and routine oral hygiene procedures as control - Group IV. The results thus
      obtained were analyzed using Statistical Package for the Social Sciences (SPSS)
      version 16. RESULTS: A statistically significant difference in the pre and post
      application scores of S. mutans (P < 0.01) count was observed in all the groups
      with CPP-ACP plus fluoride group being the most proficient. CONCLUSION: Materials
      such as fluoride varnish, CPP-ACP, and CPP-ACP plus fluoride protects the tooth
      structure, preserving the integrity of primary dentition, with the most
      encouraging results being with CPP-ACP plus fluoride.

PMID- 27891309
TI  - Evaluation of dental and bone age in iron-deficient anemic children of South
      India.
AB  - AIMS AND OBJECTIVES: Dental and bone age is very essential for the dental
      practitioner in planning treatments and is an extra source of information for the
      pediatrician, orthopedician, and endocrinologist. There are few published data
      regarding collation between dental age, bone age, and chronological age in iron
      deficiency anemic children. This study has been undertaken to evaluate and
      compare dental age, bone age, and chronological age in children with iron
      deficiency anemia. MATERIALS AND METHODS: One hundred iron-deficiency anemic
      children were selected in the age group of 8-14 years. Chronological age of the
      child was recorded by asking birth date from parents or checking school records.
      Dental age was calculated by Demirjians method and bone age was evaluated using
      Bjork, Grave, and Brown's method. Unpaired student's t-test and Pearson's
      correlation coefficient were the two statistical tests applied to compare dental,
      bone, and chronological age. RESULTS: Dental and bone age was significantly lower
      (P < 0.001) compared to chronological age. The correlation between the three ages
      was positive in both sexes. CONCLUSION: Dental and bone age retardation was a
      significant feature in our sample of 100 iron-deficient anemic children. Bone age
      and dental age are valuable parameters in assessing the overall growth of the
      child. Further studies are required to corroborate our findings.

PMID- 27891310
TI  - Assessment of oral health attitudes and behavior among students of Kuwait
      University Health Sciences Center.
AB  - AIM: The aims of this study were to assess attitudes and behavior of oral health
      maintenance among students in four faculties (Medicine, Dentistry, Pharmacy, and
      Allied Health) and to compare oral health attitudes and behavior of all students
      at Kuwait University Health Sciences Center (KUHSC) based on their academic
      level. MATERIALS AND METHODS: Students enrolled in the Faculties of Dentistry,
      Medicine, Pharmacy, and Allied Health at KUHSC were evaluated regarding their
      oral health attitudes and behavior by an e-mail invitation with a link to the
      Hiroshima University Dental Behavior Inventory survey that was sent to all 1802
      students with Kuwait University Health Sciences Center e-mail addresses. The data
      were analyzed for frequency distributions, and differences among the groups were
      assessed using the Mann-Whitney U test, Chi-square test, and Kruskal-Wallis test.
      P values less than 0.05 were considered to be statistically significant (P <
      0.05). RESULTS: The results of this study indicated that dental students achieved
      better oral health attitudes and behavior than that of their nondental
      professional fellow students (P < 0.05). Students in advanced academic levels and
      female students demonstrated better oral health attitudes and behavior.
      CONCLUSION: Dental students and students who were in advanced levels of their
      training along with female students demonstrated better oral health practices and
      perceptions than students in lower academic levels and male students,
      respectively. Additional studies for investigating the effectiveness and
      identifying areas requiring modification within the dental curriculum at KUHSC
      may be warranted.

PMID- 27891311
TI  - Comparison of antibacterial efficacy of coconut oil and chlorhexidine on
      Streptococcus mutans: An in vivo study.
AB  - AIMS: Streptococcus mutans is the most common organism causing dental caries.
      Various chemotherapeutic agents are available that help in treating the bacteria,
      with each having their own merits and demerits. Recent research has shown that
      coconut oil has anti-inflammatory and antimicrobial action. Therefore, the
      present was conducted to determine the antibacterial efficacy of coconut oil and
      to compare it with chlorhexidine. MATERIALS AND METHODS: A total of fifty female
      children aged 8-12 years were included in the study. Twenty five children were
      randomly distributed to each group, i.e., the study group (coconut oil) and the
      control group (chlorhexidine). The participants were asked to routinely perform
      oil swishing with coconut oil and chlorhexidine and rinse every day in the
      morning after brushing for 2-3 minutes. S. mutans in saliva and plaque were
      determined using a chairside method, i.e., the Dentocult SM Strip Mutans test.
      Patients were instructed to continue oil swishing for 30 days. S. mutans. counts
      in plaque and saliva on day 1, day 15, and day 30 were recorded and the results
      were compared using Wilcoxon matched pairs signed ranks test. RESULTS: The
      results showed that there is a statistically significant decrease in S. mutans.
      count from coconut oil as well as chlorhexidine group from baseline to 30 days.
      The study also showed that in comparison of coconut oil and chlorhexidine there
      is no statistically significant change regarding the antibacterial efficacy.
      CONCLUSION: Coconut oil is as effective as chlorhexidine in the reduction of S.
      mutans.

PMID- 27891312
TI  - Evaluation of Moyer's mixed dentition space analysis in Indian children.
AB  - AIM AND OBJECTIVES: Tooth size prediction values are not universal for all ethnic
      and racial groups. The present study evaluated the applicability of Moyer's mixed
      dentition space analysis in the Marwari community of Rajasthan, India. MATERIALS
      AND METHODS: The mesiodistal dimension of permanent mandibular incisors,
      maxillary and mandibular canine, and premolars of both sides were measured and
      averaged in 200 adolescents (100 males and 100 females) of the Marwari population
      in Rajasthan using digital Vernier caliper. Data were statistically analyzed
      using Student's t-test. The data were then compared with Moyer's predicted
      values. The tooth measurements of male and female participants were compared with
      unpaired t-test. RESULTS: Moyer's prediction chart was not comparable with the
      study population group. The coefficient of correlation and coefficient of
      determination in our study was 0.57 and 0.25, respectively. Mesiodistal width of
      measured teeth was lesser in females compared to males for both canine and
      premolars (P = 0.471 and P = 0.0001, respectively). CONCLUSION: There was
      significant statistical difference between values of the present study and
      Moyer's prediction values. Hence, new regression equation and prediction table
      can be used to predict mesiodistal dimensions of canine and premolars in Marwari
      children of Rajasthan.

PMID- 27891313
TI  - Effect of oral health education in the form of Braille and oral health talk on
      oral hygiene knowledge, practices, and status of 12-17 years old visually
      impaired school girls in Pune city: A comparative study.
AB  - AIM: To assess the effect of oral health education (OHE) in the form of Braille
      and combination with Oral health talk (OHT) on oral hygiene knowledge, practices,
      and status of 12-17 years old visually impaired school girls in Pune city.
      MATERIALS AND METHODS: A 6-week comparative study was conducted among 74
      residential visually impaired school girls aged 12-17 years, who were trained to
      read Braille. The participants were divided into two groups, namely, Group A (n =
      37) receiving OHE only in the form of Braille and Group B (n = 37) receiving OHE
      in form of Braille and OHT at baseline, 2, and 4-week interval. Oral health
      knowledge was assessed using a self-administered, pre-validated, pre-tested
      questionnaire typed in Marathi Braille. Assessment of oral hygiene practices and
      status was done using standardized proforma and simplified oral hygiene index
      (OHI-S), respectively, at baseline and at the end of 6 weeks. Data was analyzed
      using paired and unpaired Student's t-test. RESULTS: The results showed a
      statistically significant increase in oral health knowledge levels in Group B
      (4.95 +/- 1.66) as compared to Group A (2.97 +/- 1.28). There was a significant
      increase in the frequency of mouth-rinsing in Group B (97.3%) as compared to
      Group A (86.5%) as well as in the tongue cleaning practice in Group B (100%) as
      compared to Group A (81.1%) at the end of 6 weeks. CONCLUSION: OHE in the form of
      Braille and OHT was more effective than OHE using only Braille.

PMID- 27891315
TI  - Awareness about biomedical waste management and knowledge of effective recycling
      of dental materials among dental students.
AB  - AIMS AND OBJECTIVES: Biomedical waste management has become a concern with
      increasing number of dental practitioners in India. Being health care
      professionals, dentists should be aware regarding safe disposal of biomedical
      waste and recycling of dental materials to minimize biohazards to the
      environment. The aim of the present study was to assess awareness regarding
      biomedical waste management as well as knowledge of effective recycling and reuse
      of dental materials among dental students. MATERIALS AND METHODS: This cross
      sectional study was conducted among dental students belonging from all dental
      colleges of Bhubaneswar, Odisha (India) from February 2016 to April 2016. A total
      of 500 students (208 males and 292 females) participated in the study, which was
      conducted in two phases. A questionnaire was distributed to assess the awareness
      of biomedical waste management and knowledge of effective recycling of dental
      materials, and collected data was examined on a 5-point unipolar scale in
      percentages to assess the relative awareness regarding these two different
      categorizes. The Statistical Package for Social Sciences was used to analyzed
      collected data. RESULTS: Forty-four percent of the dental students were not at
      all aware about the management of biomedical waste, 22% were moderately aware,
      21% slightly aware, 7% very aware, and 5% fell in extremely aware category.
      Similarly, a higher percentage of participants (61%) were completely unaware
      regarding recycling and reusing of biomedical waste. CONCLUSION: There is lack of
      sufficient knowledge among dental students regarding management of biomedical
      waste and recycling or reusing of dental materials. Considering its impact on the
      environment, biomedical waste management requires immediate academic assessment
      to increase the awareness during training courses.

PMID- 27891314
TI  - Comparison of views on the need for continuing education on oral cancer between
      general dentists and oral medicine experts: A Delphi survey.
AB  - OBJECTIVES: The role of dental professionals in screening for oral cancer has
      been limited. The purpose of this study was to investigate and compare the
      educational priorities of oral medicine specialists, general dental
      practitioners, and doctors of dental surgery with regards to the diagnosis and
      management of oral cancers and potential malignant disorders. STUDY DESIGN: This
      was a longitudinal survey. MATERIALS AND METHODS: A Delphi survey was directed to
      a panel of 25 oral medicine specialists asking them to identify the major
      difficulties in diagnosing and managing patients with oral cancer or suspected
      malignancy. In a second phase, two groups of generalists were asked to express
      their ratings on the issues identified by experts. RESULTS: The response rate of
      the experts to the survey was 84%, while only 44% of the generalists
      participated. Although the three groups agreed on most of the issues, there were
      significant differences of opinions on 10 of the items proposed by specialists (P
      < 0.05 from the Kruskal-Wallis test), which were observed mainly between experts
      and general dental practitioners (P < 0.017 from the Mann-Whitney U test). The
      opinion of the participants about future investments in the field of education
      resulted in similar results (P > 0.05 from the Chi-square test), with the
      specialists ranking highest on mandatory annual thematic courses, while the
      generalists prioritizing more interactive and extensive pre-graduation courses on
      oral cancer detection. CONCLUSION: This study confirms a clear need to improve
      the educational foundation on oral cancer by a didactic process starting with pre
      graduation courses that should involve National Health Care Services, National
      Dental Associations, and academia.

PMID- 27891316
TI  - Histologic and histomorphometric evaluation of two grafting materials Cenobone
      and ITB-MBA in open sinus lift surgery.
AB  - AIMS AND OBJECTIVES: Alveolar ridge reduction caused after tooth extraction can
      be minimized through ridge preservation and application of graft materials. The
      aim of this study was to compare the histologic and histomorphometric aspects of
      bone particulated allografts, Cenobone and ITB-MBA, in the reconstruction of
      vertical alveolar ridge after maxillary sinus augmentation. MATERIALS AND
      METHODS: This clinical trial was performed among 20 patients. The participants
      were randomly divided into two groups of 10 participants. The first group
      received Cenobone and the second group received ITB-MBA. Tissue samples were
      prepared 6 months later at the time of implant installation and after successful
      maxillary sinus floor augmentation. Tissue sections were examined under a light
      microscope. The data were analyzed by Chi-square and t-test. RESULTS: The mean
      trabecular thickness of the samples in the Cenobone group was 13.61 +/- 7.47 MUm
      compared to 13.73 +/- 7.37 MUm in the ITB-MBA group (P = 0.93). A mild
      inflammation process (Grade 1) was detected in both the groups. The amount of
      remaining biomaterial in the Cenobone group was estimated to be 8 +/- 19% vs. 7
      +/- 12% in the ITB-MBA group (P = 0.30). Bone formation was reported 49.71% in
      the Cenobone group vs. 40.76% in the ITB-MBA group (P = 0.68). The mean newly
      formed vessel in the Cenobone group was 0.64 +/- 0.7 vs. 1.5 +/- 2.3 in the ITB
      MBA group (P = 0.14). CONCLUSIONS: There was no significant difference between
      the two groups of patients regarding trabecular thickness, remaining biomaterial
      allograft, and the density of blood vessels after sinus floor elevation; hence,
      there was no difference between the two groups regarding implant outcome. More
      designed studies as randomized controlled trials and controlled clinical trials,
      which evaluate the long-term implant outcome; comparing the different bone graft
      materials is also required to improve evidence on survival and success rate.

PMID- 27891317
TI  - Outcome of tobacco cessation in workplace and clinic settings: A comparative
      study.
AB  - AIMS AND OBJECTIVES: Several biological, social, and cultural factors contribute
      to the poor outcome of tobacco cessation interventions. Inability to engage large
      number of participants is one of the major identifiable factors. The objective of
      this study was to compare the outcome of tobacco cessation interventions in the
      clinical and workplace settings. MATERIALS AND METHODS: In the present study, we
      recruited 100 participants in tobacco cessation clinic (TCC) group and workplace
      group (50 participants in each). Both the groups were regularly intervened and
      were followed up regularly at 2 weeks, 4 weeks, 3 months, and 6 months. Active
      interventions in the form of awareness lectures, focused group discussions, and
      if needed, pharmacotherapy (nicotine/non-nicotine replacement therapy) was
      carried out for all participants. The outcome was assessed as no change, harm
      reduction (>50% reduction), complete cessation, and drop out. Statistical
      analysis of the data was done using the Statistical Package for the Social
      Sciences version 21.0. RESULTS: At the end of 1 month, there was higher tobacco
      cessation rate in the workplace group versus TCC group (n = 22, 44% vs n = 9,
      18%; P < 0.0001). The tobacco cessation rate was maintained even after 6 months
      of intervention (n = 30, 60% vs n = 12, 24%; P = 0.002) and dropout rate was also
      lower among the workplace group than the TCC group (n = 14, 28% vs n = 27, 54%; P
      < 0.0001). CONCLUSIONS: Our study findings suggest that the workplace setting has
      superior outcome in tobacco cessation and harm reduction than clinical setting.
      In addition, it is associated with low dropout rate and the cessation effect is
      maintained over a period of 6 months.

PMID- 27891318
TI  - Complication of improper management of sodium hypochlorite accident during root
      canal treatment.
AB  - Sodium Hypochlorite (NaOCl) is a common irrigation solution used in root canal
      treatment. It has strong antibacterial and tissue dissolving properties.
      Nevertheless, it has some serious complications, some of which are life
      threatening. A young male presented with severe chemical burn of the right
      infraorbital area and partial necrosis of the hard palate resulting from
      extrusion of NaOCl during root canal treatment of the upper right 2nd molar
      tooth. The patient had a facial scar, and mucosal damage healed nearly
      completely. Several precautions must be taken during NaOCl use to prevent the
      spread of the solution into surrounding tissues. Early recognition of NaOCl
      accident and proper immediate management are important to achieve the best
      possible outcome.

PMID- 27891319
TI  - Hyaluronic acid: Hope of light to black triangles.
AB  - Interdental papilla construction, especially in the esthetic area, is one of the
      most challenging tasks. Interdental papilla loss might occur due to several
      reasons as a consequence of periodontal surgery or trauma. The purpose of this
      study is to report the reconstruction of lost interdental papilla using
      hyaluronic acid gel. Hyaluronic acid is a glycosaminoglycan molecule with anti
      inflammatory, anti-edematous properties on periodontal tissues invaded by
      submicrobial flora. It enhances wound healing and accelerates periodontal repair
      and regeneration. In addition to the field of dentistry, it has been used in
      other fields such as orthopedics, ophthalmology, and dermatology. It shows growth
      factor interaction, regulates osmotic pressure, and enhances tissue lubrication,
      which helps in maintaining the structural and homeostatic integrity of tissues,
      hence resulting in beneficial effect on lost interdental papilla. This study was
      aimed to reconstruct the lost interdental papilla by injecting 0.2% hyaluronic
      acid via nonsurgical approach. It is a noninvasive approach which reduces
      patient's postoperative discomfort with marked variations in the volume of
      interdental papilla before and after the procedure. As sufficient information is
      not available regarding the effectiveness of hyaluronic acid in interdental
      papilla construction, this study was conducted.

PMID- 27891320
TI  - The Association of VDAC with Cell Viability of PC12 Model of Huntington's
      Disease.
AB  - It is becoming increasingly apparent that mitochondria dysfunction plays an
      important role in the pathogenesis of Huntington's disease (HD), but the
      underlying mechanism is still elusive. Thus, there is a still need for further
      studies concerning the upstream events in the mitochondria dysfunction that could
      contribute to cell death observed in HD. Taking into account the fundamental role
      of the voltage-dependent anion-selective channel (VDAC) in mitochondria
      functioning, it is reasonable to consider the channel as a crucial element in HD
      etiology. Therefore, we applied inducible PC12 cell model of HD to determine the
      relationship between the effect of expression of wild type and mutant huntingtin
      (Htt and mHtt, respectively) on cell survival and mitochondria functioning in
      intact cells under conditions of undergoing cell divisions. Because after 48 h of
      Htt and mHtt expression differences in mitochondria functioning co-occurred with
      differences in the cell viability, we decided to estimate the effect of Htt and
      mHtt expression lasted for 48 h on VDAC functioning. Therefore, we isolated VDAC
      from the cells and tested the preparations by black lipid membrane system. We
      observed that the expression of mHtt, but not Htt, resulted in changes of the
      open state conductance and voltage-dependence when compared to control cells
      cultured in the absence of the expression. Importantly, for all the VDAC
      preparations, we observed a dominant quantitative content of VDAC1, and the
      quantitative relationships between VDAC isoforms were not changed by Htt and mHtt
      expression. Thus, Htt and mHtt-mediated functional changes of VDAC, being
      predominantly VDAC1, which occur shortly after these protein appearances in
      cells, may result in differences concerning mitochondria functioning and
      viability of cells expressing Htt and mHtt. The assumption is important for
      better understanding of cytotoxicity as well as cytoprotection mechanisms of
      potential clinical application.

PMID- 27891321
TI  - Protective Immunity Elicited by Oral Immunization of Mice with Salmonella
      enterica Serovar Typhimurium Braun Lipoprotein (Lpp) and Acetyltransferase (MsbB)
      Mutants.
AB  - We evaluated the extent of attenuation and immunogenicity of the DeltalppAB and
      DeltalppAB DeltamsbB mutants of Salmonella enterica serovar Typhimurium when
      delivered to mice by the oral route. These mutants were deleted either for the
      Braun lipoprotein genes (lppA and lppB) or in combination with the msbB gene,
      which encodes an acetyltransferase required for lipid A modification of
      lipopolysaccharide. Both the mutants were attenuated (100% animal survival) and
      triggered robust innate and adaptive immune responses. Comparable levels of IgG
      and its isotypes were produced in mice infected with wild-type (WT) S.
      typhimurium or its aforementioned mutant strains. The DeltalppAB DeltamsbB mutant
      immunized animals resulted in the production of higher levels of fecal IgA and
      serum cytokines during later stages of vaccination (adaptive response). A
      significant production of interleukin-6 from T-cells was also noted in the
      DeltalppAB DeltamsbB mutant-immunized mice when compared to that of the
      DeltalppAB mutant. On the other hand, IL-17A production was significantly more in
      the serum of DeltalppAB mutant-immunized mice (innate response) with a stronger
      splenic T-cell proliferative and tumor-necrosis factor-alpha production. Based on
      2-dimensional gel analysis, alterations in the levels of several proteins were
      observed in both the mutant strains when compared to that in WT S. typhimurium
      and could be associated with the higher immunogenicity of the mutants. Finally,
      both DeltalppAB and DeltalppAB DeltamsbB mutants provided complete protection to
      immunized mice against a lethal oral challenge dose of WT S. typhimurium. Thus,
      these mutants may serve as excellent vaccine candidates and also provide a
      platform for delivering heterologous antigens.

PMID- 27891322
TI  - Epigenetics in Schistosomes: What We Know and What We Need Know.
AB  - Schistosomes are metazoan parasites and can cause schistosomiasis. Epigenetic
      modifications include DNA methylation, histone modifications and non-coding RNAs.
      Some enzymes involved in epigenetic modification and microRNA processes have been
      developed as drugs to treat the disease. Compared with humans and vertebrates, an
      in-depth understanding of epigenetic modifications in schistosomes is starting to
      be realized. DNA methylation, histone modifications and non-coding RNAs play
      important roles in the development and reproduction of schistosomes and in
      interactions between the host and schistosomes. Therefore, exploring and
      investigating the epigenetic modifications in schistosomes will facilitate drug
      development and therapy for schistosomiasis. Here, we review the role of
      epigenetic modifications in the development, growth and reproduction of
      schistosomes, and the interactions between the host and schistosome. We further
      discuss potential epigenetic targets for drug discovery for the treatment of
      schistosomiasis.

PMID- 27891323
TI  - Reduced CX3CL1 Secretion Contributes to the Susceptibility of Oral Leukoplakia
      Associated Fibroblasts to Candida albicans.
AB  - Candida leukoplakia (OLK) is a kind of oral leukoplakia combined with chronic
      candidal infection, which plays an important role in the malignant transformation
      of OLK. However, little is known about the etiology, including susceptibility of
      leukoplakia to candidal adhesion, invasion and infection. Some antimicrobial
      peptides secreted by oral epithelial cells or fibroblasts potentially have
      antifungal activities against Candida albicans (C. albicans). In this study, we
      established three co-culture models to simulate different C. albicans-fibroblasts
      interactions during progression of candida leukoplakia. The susceptibility of
      oral leukoplakia-associated fibroblasts (LKAFs) to C. albicans and its underlying
      mechanism were determined. Samples of 14 LKAFs and 10 normal fibroblasts (NFs)
      were collected. The co-culture models showed that LKAFs had promoted the
      adhesion, invasion, and survival of C. albicans compared with NFs. CX3CL1, a
      chemokine with antifungal activity, was less abundant in LKAFs than NFs.
      Overexpression of CX3CL1 via transfection in LKAFs could partly restore the
      resistance to C. albicans. We also showed that inhibition of ERK could suppress
      CX3CL1 secretion. While phosphor-ERK was inhibited in LKAFs compared with NFs.
      Besides, the mRNA expression of a shedding enzyme for CX3CL1, disintegrin and
      metalloproteinase domain (ADAM) 17 was decreased in LKAFs than NFs. In
      conclusion, LKAFs produced and secreted less CX3CL1 by inhibiting the ERK
      signaling pathway, thereby contributing to impaired cell resistance to C.
      albicans.

PMID- 27891324
TI  - High-throughput cell-based compound screen identifies pinosylvin methyl ether and
      tanshinone IIA as inhibitors of castration-resistant prostate cancer.
AB  - Current treatment options for castration-resistant prostate cancer (CRPC) are
      limited. In this study, a high-throughput screen of 4910 drugs and drug-like
      molecules was performed to identify antiproliferative compounds in androgen
      ablated prostate cancer cells. The effect of compounds on cell viability was
      compared in androgen ablated LNCaP prostate cancer cells and in LNCaP cells grown
      in presence of androgens as well as in two non-malignant prostate epithelial
      cells (RWPE-1 and EP156T). Validation experiments of cancer specific anti
      proliferative compounds indicated pinosylvin methyl ether (PSME) and tanshinone
      IIA as potent inhibitors of androgen ablated LNCaP cell proliferation. PSME is a
      stilbene compound with no previously described anti-neoplastic activity whereas
      tanshinone IIA is currently used in cardiovascular disorders and proposed as a
      cancer drug. To gain insights into growth inhibitory mechanisms in CRPC, genome
      wide gene expression analysis was performed in PSME- and tanshinone IIA-exposed
      cells. Both compounds altered the expression of genes involved in cell cycle and
      steroid and cholesterol biosynthesis in androgen ablated LNCaP cells. Decrease in
      androgen signalling was confirmed by reduced expression of androgen receptor and
      prostate specific antigen in PSME- or tanshinone IIA-exposed cells. Taken
      together, this systematic screen identified a novel anti-proliferative agent,
      PSME, for CRPC. Moreover, our screen confirmed tanshinone IIA as well as several
      other compounds as potential prostate cancer growth inhibitors also in androgen
      ablated prostate cancer cells. These results provide valuable starting points for
      preclinical and clinical studies for CRPC treatment.

PMID- 27891325
TI  - Effect of Tocopheryl Acetate on Maternal Cigarette Smoke Exposed Swiss Albino
      Mice Inbred Fetus.
AB  - INTRODUCTION: Cigarette smoking is worldwide problem which can be correlated with
      teratogenicity. Tocopheryl acetate plays as an antioxidant against the oxidative
      stress evolved by cigarette smoke exposure during pregnancy. AIM: To study the
      effect of maternal exposure to cigarette smoke and Tocopheryl acetate on fetuses
      of mice. MATERIALS AND METHODS: Pregnant mice randomly assigned to different
      groups (Group I (control), Group II (Tocopheryl acetate), Group III(soyabean oil
      used as vehicle for Tocopheryl acetate), Group IV (Cigarette smoke Exposed),
      Group V (Cigarette smoke exposed plus Tocopheryl acetate) and Group VI(Cigarette
      smoke exposed plus soyabean oil) were exposed to cigarette smoke 3 times a day
      for 20 minutes each time and Tocopheryl acetate with dose of 200mg/kg/day in
      0.3ml of soyabean oil as vehicle orally through oral gavage from the 5th day of
      gestation to 15th day. RESULTS: Cigarette smoke exposed mice showed significant
      fetal weight loss, resorption, placental anomalies, severe growth retardation,
      venous congestion, haemorrhage, limbs defects and enphalocele. Negligible
      abnormalities were seen among the control and Tocopheryl acetate group. Cigarette
      smoke exposed group with Tocopheryl acetate exhibited weight gain among the fetus
      as well as no gross abnormalities. The oxidative stress was significantly
      increased by increasing Malondialdehyde (MDA) 293+/-81.57 MUmol/mg (p<0.0001) and
      decreasing Superoxide Dismutase (SOD) 1.43 +/- 0.23mg/ml, (p<0.0001) Reduced
      Glutathione (GR) 0.017+/-0.002mg/ml, (p<0.01) and Catalase (CAT) 0.248+/
      0.005mg/ml, (p<0.0001). Tocopheryl acetate induced group significantly maintained
      the oxidative stress with all p <0.0001. CONCLUSION: It can be concluded that
      Tocopheryl acetate may have an ameliorating effect on the cigarette smoke during
      pregnancy on fetus.

PMID- 27891326
TI  - Determining Angle of Humeral Torsion Using Image Software Technique.
AB  - INTRODUCTION: Several researches have been done on the measurement of angles of
      humeral torsion in different parts of the world. Previously described methods
      were more complicated, not much accurate, cumbersome or required sophisticated
      instruments. AIM: The present study was conducted with the aim to determine the
      angles of humeral torsion with a newer simple technique using digital images and
      image tool software. MATERIALS AND METHODS: A total of 250 dry normal adult human
      humeri were obtained from the bone bank of Department of Anatomy. The length and
      mid-shaft circumference of each bone was measured with the help of measuring
      tape. The angle of humeral torsion was measured directly from the digital images
      by the image analysis using Image Tool 3.0 software program. The data was
      analysed statistically with SPSS version 17 using unpaired t-test and Spearman's
      rank order correlation coefficient. RESULTS: The mean angle of torsion was 64.57
      degrees +/-7.56 degrees . On the right side it was 66.84 degrees +/-9.69 degrees
      , whereas, on the left side it was found to be 63.31+/-9.50 degrees . The mean
      humeral length was 31.6 cm on right side and 30.33 cm on left side. Mid shaft
      circumference was 5.79 on right side and 5.63 cm on left side. No statistical
      differences were seen in angles between right and left humeri (p>0.001).
      CONCLUSION: From our study, it was concluded that circumference of shaft is
      inversely proportional to angle of humeral torsion. The length and side of
      humerus has no relation with the humeral torsion. With advancement of digital
      technology, it is better to use new image softwares for anatomical studies.

PMID- 27891327
TI  - Analysis of Fetal Palate to Assist Pre-natal Ultrasound.
AB  - INTRODUCTION: Cleft palate is one of the major facial congenital malformation in
      newborns. Pre-natal detection of this malformation is limited to detection of
      clefting of hard palate but isolated soft palate clefting still remains challenge
      for sonologists. As Indian literature is limited present study was attempted to
      provide dimensions and position of fetal palate by digitized images. AIM: To
      study dimensions, position and differences in parameters between second and third
      trimester fetuses. MATERIALS AND METHODS: Median sagittal section of 32 formalin
      fixed fetuses was selected from the Department of Anatomy, St John's Medical
      College, Bangalore, Karnataka, India. Anatomical landmarks-The Nasion (N),
      Sellaturcica (S), Anterior Nasal Spine (ANS), Posterior Nasal Spine (PNS), tip of
      Uvula (U) were marked on sections. Length of hard palate (from ANS to PNS),
      Length of soft palate (from PNS to U), Hard palate/soft palate angle was defined.
      The anterior position of soft palate and its posterior position in relation to
      anterior cranial base were marked as N-S-PNS and N-S-U angle, respectively. The
      measurements were acquired directly from the digitized images using ImageJ
      software. Statistical analysis was done using SPSS 16. RESULTS: The mean values
      of ANS-PNS and PNS-U were 23.59+/-3.69mm and 14.39+/-2.70mm, respectively. The
      mean values of hard palate/soft palate angle, N-S-PNS and N-S-U angle were
      144.720+/-11.11,51.150+/-9.09 and 93.370+/-9.58, respectively. Significant
      difference was noted between trimesters for length of hard and soft palate but
      not for palatal angles. CONCLUSION: During Pre-natal assessment of cleft palate,
      it is important for sonologist to keep in mind that the dimensions of palate
      proportionately increased in last two trimesters while the position remains
      constant.

PMID- 27891328
TI  - Abnormal Course of Right Coronary Artery Together with Variant Left Coronary
      Artery and Partial Atresia of Cicumflex Artery.
AB  - Heart is supplied by right and left coronary arteries. Therefore, the knowledge
      of normal and variant anatomy of both these arteries and their configurations is
      indispensable for proper understanding of diagnosis and treatment of dreaded
      cardiac diseases. During routine cadaveric dissection, a heart of an adult female
      with anomalous course of Right Coronary Artery (RCA), new variant of trifurcated
      Left Coronary Artery (LCA) and partial atresia of circumflex (CX) artery was
      detected. Trifurcation of LCA into anterior interventricular, CX and a ramus
      intermedius without giving accessory branches has been reported. But in the
      present case, a variant trifurcation was found having rare configuration i.e.,
      the interventricular branch gave two additional branches, a new variant along
      with ramus intermedius also giving an additional branch another new variant
      followed by partially hypoplastic circumflex artery. Besides this, RCA has an
      aberrant course modifying normal supply of heart. This rare configuration of
      coronary arteries will facilitate the cardiac surgeons to improve the
      understanding of defects of coronary arteries and planning of angiography,
      coronary by bypass grafting and other surgical interventions, radiologists for
      refining interpretation of imagery and anatomists for new variants.

PMID- 27891329
TI  - Effects of Lead in Various Preparatory Stages of Nagabhasma on Function and
      Histopathology of Cornu Ammonis of Hippocampus.
AB  - INTRODUCTION: Heavy metals are frequently used in the preparations of
      traditional/folk medicines. One such preparation in Ayurveda is Nagabhasma, in
      which lead is the main ingredient. Lead is non-essential element to the human
      body and is known toxic substance to many organ systems. However, it is claimed
      that, the highly toxic metallic lead will be converted into health beneficial
      organo-metallic compound when raw lead is subjected to various traditional
      methods of purification during preparation as mentioned in the ancient medicinal
      system. AIM: The present study is designed to evaluate the effect of such
      detoxification of lead in various stages of authentically prepared Nagabhasma on
      the learning and memory. MATERIALS AND METHODS: Using half of the human
      equivalent doses of traditionally prepared Nagabhasma, at intermittent stages of
      its preparation were fed orally to healthy Wistar rats for 30 days. After
      treatment, the immediate effect and residual effect after 2 months was evaluated
      by subjecting them to passive avoidance test. Then rats were sacrificed and
      hippocampus was collected for histopathological evaluation. RESULTS: Pure lead
      treated animals showed deficit in learning and memory which is indicated by
      spending more time in the dark compartment in passive avoidance test. However,
      animals treated with stage 1 to 4 Nagabhasma showed gradual increase in the
      memory and learning. This observation is substantiated by the findings of the
      histopathology of the Cornu Ammonis (CA) region of hippocampus. CONCLUSION: The
      results of the present study indicate that, the metallic toxicity of the lead
      used in the preparation of bhasma was gradually decreased from stage 1 to stage 4
      of preparation. Therefore, the traditional way of preparing the metallic bhasma
      is very critical in eliminating the possible health hazardous metallic lead
      toxicity.

PMID- 27891330
TI  - Evaluation of Lipid Profile and Apolipoproteins in Essential Hypertensive
      Patients.
AB  - INTRODUCTION: Essential hypertension is one of the most common diseases of the
      Indian population contributing greatly to the morbidity, mortality and economic
      burden. It has a strong association with cardiovascular disease and abnormal
      lipid metabolism. Not only the traditional lipid parameters, but also the novel
      lipid components like Apo A1 and Apo B100 also have been identified to play a
      role. AIM: The present study was done to evaluate serum lipid profile and Apo A1,
      Apo B 100 in essential hypertensive patients and correlate their values with the
      degree of hypertension. MATERIALS AND METHODS: Fasting samples from 55 age and
      sex matched controls and 55 essential hypertensives were tested for plasma
      glucose, serum urea, creatinine, lipid profile, apo A1 and apo B100. The cases
      were subclassified based on the severity of hypertension according to JNC
      criteria. RESULTS: The study showed a significantly raised value for serum
      cholesterol, triacylglycerol, Low Density Lipoprotein (LDL), Very Low-Density
      Lipoprotein (VLDL) in the hypertensive patients than the control group whereas
      serum High-Density Lipoprotein (HDL) registered a fall in the cases. Apo A1
      revealed a non-significant fall in the hypertensive patients. In contrast, there
      was a rise in the serum apo B100 in the cases. Apo B100/apo A1 ratio was
      significantly raised in both stage I and stage II hypertensive patients in
      comparision to the controls. When correlated, serum apo A1 revealed a negative
      association where as serum apo B 100 showed a positive association with systolic
      and diastolic bloood pressure. Both LDL/HDL and apoB100/apo A1 and apo B100
      revealed a significant positive association with both SBP and DBP. However,
      apoB100/apo A1 revealed a more positive association in comparision to LDL/HDL
      ratio (r=0.749, p<0.001, r=0.756, p<0.001 vs r=0.336, p<0.000, r=0.312, p<0.001).
      CONCLUSION: Apo B100/apoA1 has emerged as an important complementary parameter in
      addition to traditional lipid ratio for evaluation of risk for future
      cardiovascular disease.

PMID- 27891331
TI  - Association of Diabetic Nephropathy and Liver Disorders.
AB  - INTRODUCTION: Liver disorder is known to be a risk factor for Diabetes Mellitus
      (DM) and diabetic patients are at risk of developing liver disorders. Association
      of liver and renal disease is less explored in the field of research; hence, we
      conducted a retrospective study on this. AIM: To compare the renal and liver
      profiles of type II DM patients compared to healthy controls and find the
      association between the two profiles in diabetics. MATERIALS AND METHODS: The
      renal and liver profiles of 68 type II DM patients and 58 controls were compared.
      Estimated Glomerular Filtration Rate (GFR) (eGFR) was calculated using
      Modification of Diet in Renal Disease (MDRD) formula and was taken as a tool to
      grade different stages of diabetic nephropathy. Comparison of liver profiles
      between different stages of diabetic nephropathy was done. Correlations and
      associations were studied between eGFR and liver enzymes and Bilirubin. RESULTS:
      A significant elevation in Total Bilirubin (TB) (p< 0.15), Direct Bilirubin (DB)
      (p< 0.0035), Aspartate Amino Transferase (AST) and Alanine Amino Transferase
      (ALT) (p<0.0001) levels in diabetics was noted. An elevated eGFR and a
      significant correlation between eGFR and liver enzymes were observed. A
      significant association between liver and renal disease has been obtained in
      diabetics (p=0.0136). CONCLUSION: Significantly, high liver function tests and
      low eGFR were observed in type II diabetics. A significant positive correlation
      between liver enzymes (AST and ALT) and eGFR suggest a possible association
      between liver and kidney functions in DM.

PMID- 27891332
TI  - Is dilution important: Factitious Total Creatine Kinase in case of
      Rhabdomyolysis?
AB  - Factitious test reports may result in incorrect diagnosis and incorrect
      management. Such incorrect diagnosis can be prevented by a vigilant biochemist.
      We report a case of Rhabdomyolysis presenting with extremely low total Creatine
      Kinase (CK) levels which was factitious. Running the sample in dilution resulted
      in a very high value of total CK which could have been missed if the sample was
      not run in dilution and the diagnosis of Rhabdomyolysis could have been missed.

PMID- 27891333
TI  - Correct Blood Sampling for Blood Gas Analysis.

PMID- 27891334
TI  - Life Orientation Test- Revised (LOT-R) Versus Academic Score in Various First
      Year Health Professional Students.
AB  - INTRODUCTION: Health field per se requires mental, physical and psychological
      steadiness and wellbeing. In modern times decline in psychological and physical
      health has been observed in student after admission in health education program.
      Factors like perfectionism, self-esteem, personal and professional consequence
      have affected their academic score directly or indirectly. Life Orientation Test
      Revised (LOT-R) instrument measures optimism in relation to self-esteem of
      individual. A better score will show more confidence level of the student. AIM:
      To find an association of LOT-R with the academic score of health professional
      students and assess gender variation. MATERIALS AND METHODS: A total of 350
      students enrolled for academic year 2015-16 in health professional program of
      medicine, dental and physiotherapy institutes of Sumandeep Vidyapeeth University
      were considered. Non-randomized and purposive study was done by providing LOT-R
      questionnaire to students. Average academic score of Anatomy and Physiology
      course was used for analysis excluding the biochemistry due to non-availability
      of tangible data at the time of study. Data was collected, analysed statistically
      using independent t-test, ANOVA with post-hoc and correlation analysis. RESULT:
      Statistical significant for one-way ANOVA was assessed for academic score between
      the group of health professional students. While no statistical correlation of
      significance was observed for LOT-R score with that of academic score. As per
      gender distribution there was no statistical significant observation for LOT-R
      score within the groups. CONCLUSION: The present study highlighted the need of
      student's counseling for their approach towards health education; as their
      career. Psychological self-reliance and optimism improves the academic score. A
      study needs to be compared with the socio-economic status of the student to have
      a better understanding of the LOT-R.

PMID- 27891335
TI  - A Comparative Evaluation of Different Diagnostic Modalities in the Diagnosis of
      Typhoid Fever Using a Composite Reference Standard: A Tertiary Hospital Based
      Study in Central India.
AB  - INTRODUCTION: Enteric fever, caused by Salmonella spp. is a major cause of
      morbidity and mortality worldwide and endemic in many developing countries
      including India and other South-East Asian countries. Blood culture is regarded
      as the gold standard for diagnosis. Currently, the standard serological method is
      tube agglutination with moderate sensitivity and specificity. Dot blot assay
      detecting IgM and IgG antibodies to a specific 50kD Outer Membrane Protein (OMP)
      antigen of Salmonella spp. is a simple, reliable, affordable and rapid test which
      can help in the early diagnosis of typhoid fever. AIM: To systematically evaluate
      the different diagnostic modalities against a composite reference standard for
      the better diagnosis of typhoid fever in clinically suspected cases of typhoid
      fever. MATERIALS AND METHODS: This cross-sectional, prospective analytical study
      was carried out at a tertiary care hospital attached to Medical College in
      central India from November 2011 to June 2013. A total of 163 blood samples,
      collected aseptically from patients clinically diagnosed of enteric fever, were
      tested using various component tests like blood culture, Tube Widal and Dot
      Enzyme Immuno Assay (Dot EIA) for IgG and/or IgM. Composite Reference Standard
      (CRS) was created for defining the confirmed cases of typhoid fever using the
      component tests, wherein culture positive and in absence of culture positivity
      any two component test positive patients were taken as confirmed cases. All the
      component tests were evaluated against the CRS for sensitivity, specificity, PPV
      and NPV and their significance in relation to the duration of illness using
      statistical tests of significance. RESULTS: Blood culture was positive in 16
      (9.81%) whereas, Tube Widal, IgM, IgG and IgM+IgG in combination were positive in
      88(54%), 58(35.58%), 30 (18.40%) and 75 (46.01%) respectively. Using a two test
      criteria of CRS framed, a total of 104 patients were considered as confirmed
      cases. Though specificity of blood culture was 100%, the sensitivity was low with
      significant detection rate in 1st week of illness. Tube Widal showed a
      sensitivity of 65.38% and specificity of 89.83% with significant detection rate
      in 2nd week. Dot blot assay for IgM, IgG and Combined IgM and IgG showed a
      sensitivity of 71.15%, 65.28% and 51.72% respectively whereas, the specificity
      was 10.16%, 47.45% and 74.57% respectively with significant detection rate in 2nd
      and 3rd week of illness. CONCLUSION: It can be concluded that though blood
      culture is still the gold standard, Dot blot assay found to have high sensitivity
      and good specificity might be a practical alternative test for the rapid
      diagnosis of typhoid fever if interpreted with care particularly using a
      composite reference standard. Further, it is reliable, simple to perform and
      rapid; results being available in 1 hour when compared to 48 hours for blood
      culture and 18 hours for Tube Widal test.

PMID- 27891336
TI  - Mycobacterium tuberculosis Beijing Genotype in Western Iran: Distribution and
      Drug Resistance.
AB  - INTRODUCTION: Mycobacterium tuberculosis Beijing genotype is gaining importance
      all over the world because this genotype is highly prevalent in several areas and
      is also frequently associated with drug resistance. AIM: To identify and
      determine the frequency of Beijing genotype and mix infection with Beijing and
      non-Beijing in west of Iran and analyse the association between Beijing genotype
      and drug resistance. MATERIALS AND METHODS: This cross-sectional study was
      conducted on 146 Tuberculosis (TB) samples collected at the TB reference
      laboratory in Kermanshah west of Iran from January 2014 to February 2015,
      Mycobacterium tuberculosis isolates from sputum samples, detected by microcopy,
      biochemical tests and solid culture were included and then the confirmed samples
      with Cepheid Xpert MTB/RIF assay were subjected to drug susceptibility tests for
      rifampicin, isoniazid, ethambutol using proportional method. The prevalence rate
      of Beijing and non-Beijing genotype was determined by Multiplex- Polymerase Chain
      Reaction (PCR). RESULT: A total of 15/146 (10%) isolates were diagnosed as
      Beijing genotypes and the remaining 131/146(90%) isolates were non-Beijing
      genotypes by Multiplex PCR method. Among the 15 Beijing cases, 14 samples have
      shown mix infection indicating the presence of both Beijing and non-Beijing
      strains in samples. Three isolates from all cases were drug resistant.
      Interestingly all drug resistance isolates were from Beijing genotype which shows
      strong association between drug resistance and Beijing genotype. Also this
      genotype was more prevalent in younger age-group people (p=0.035). CONCLUSION:
      Frequency of Beijing genotype in west of Iran is more than other sites of Iran
      but less than Asia. According to our result, mix infections with Beijing and non
      Beijing, had the most prevalence therefore we should be concerned more about mix
      infections. Multiplex-PCR method is feasible, trustworthy and can distinguish mix
      infections. It is suggested to perform spoligotyping in addition to multiplex PCR
      method to discriminate mix infections.

PMID- 27891337
TI  - High Seroprevalence of Dengue Virus Infection in Blood Donors From Delhi: A
      Single Centre Study.
AB  - INTRODUCTION: The risk of transfusion transmitted dengue has been increasingly
      recognized. Blood donors in an endemic area like Delhi may serve as a potential
      vehicle for transmission of the infection. Moreover, prevalence of infection in
      them would be representative of the true picture of dengue in a population. AIM:
      To determine the prevalence of dengue virus infection in blood donors in a
      tertiary care centre. MATERIALS AND METHODS: A total of 200 blood donors were
      recruited in the study after obtaining informed consent in the Institute of Liver
      and Biliary Sciences, New Delhi in July and August 2012. Data regarding clinical
      and demographic characteristics was collected using a preformed questionnaire.
      Blood samples obtained were subjected to anti-dengue IgM and IgG ELISA as well as
      semi-nested Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) for dengue
      RNA. RESULTS: Of the study subjects, most were men (97%) with a median age of 28
      years (range 19-51 years). Anti-dengue IgG was positive in 116 cases (58%) while
      IgM was seen in 27cases (13.5%). Of them, in 25 (12.5%) cases both IgG and IgM
      were positive, while only two (1%) cases tested positive for IgM alone. None of
      the blood donors were found to be viremic on screening using Nested RT-PCR. A
      clear increase of IgG seroprevalence with age was evident. No difference in the
      seroprevalence rates in urban vs. rural areas was seen. CONCLUSION: High
      seroprevalence of dengue infection was seen in healthy asymptomatic blood donors.
      Though evidence of acute infection was found in some, none were found to be
      viremic. Larger studies are required to quantify the risk and provide strong
      evidence for policies to be made.

PMID- 27891338
TI  - Non-O157:H7 Shiga Toxin Producing Diarrhoeagenic Escherichia coli (STEC) in
      Southern India: A Tinderbox for Starting Epidemic.
AB  - INTRODUCTION: Outbreaks due to non-O157:H7 Shiga toxin producing Escherichia coli
      (STEC) resulting in Haemolytic Uraemic Syndrome (HUS) have garnered much
      attention because of associated mortality transcending across continents and also
      because diarrhoea due to E.coli itself is rare in developed countries. The actual
      incidence of non-O157:H7 STEC in sporadic acute diarrhoea is not fully
      elucidated, both in developing as well as in developed countries. Due to larger
      extent of faecal-oral transmission in developing countries it is prudent to look
      for non-O157: H7 STEC in such epidemiological settings because of very high
      potential to spread across larger geographical regions and cause life threatening
      illness. AIM: To determine the extent of acute diarrhoea caused by Shiga toxin
      producing E. coli and measure their genotypic diversity. MATERIALS AND METHODS:
      The study was designed as a cross-sectional study and conducted between 2009-2011
      in department of Microbiology at JN Medical College Belgaum (Karnataka) and
      Regional Medical Research Center, Belgaum (RMRC-ICMR). Stool samples from 300
      sporadic cases of acute diarrhoea were processed by microscopy, culture, for the
      identification of diarrhoeagenic pathogens viz. Vibrio cholera, Shigella spp.,
      Salmonella spp. and protozoan parasites. PCR was performed for the detection of
      eae and stx genes in E. coli isolates. Their relatedness was determined by Random
      Amplification of Polymorphic DNA (RAPD). RESULTS: PCR detected stx along with eae
      in 23.2% culture isolates of E.coli isolated from diarrhoea samples. Only three
      isolates were identified as STEC by serology as O59, O60 and O69 serotypes.
      Eleven clones were detected by RAPD fingerprinting in the 46 STEC isolates.
      CONCLUSION: Non-O157:H7 STEC are prevalent in this region and laboratories shall
      look beyond O157:H7 serotype of E.coli. These isolates have potential of causing
      outbreaks transcending borders. Hence they shall be reported and efforts be made
      to identify their sources and prevent spread.

PMID- 27891339
TI  - Bacteriological Profile of Isolates From Urine Samples in Patients of Benign
      Prostatic Hyperplasia and or Prostatitis Showing Lower Urinary Tract Symptoms.
AB  - INTRODUCTION: The incidence of Benign Prostatic Hyperplasia (BPH) or Prostatitis
      is increasing considerably worldwide. The Lower Urinary Tract Symptoms (LUTS) due
      to bacterial aetiology are one of the common factors for the complications among
      the patients. AIM: To determine the bacterial agents and their antibiotic
      sensitivity pattern from the urine samples of patients of BPH or Prostatitis
      showing symptoms of LUTS. MATERIALS AND METHODS: The cross-sectional study was
      carried out in the Department of Microbiology of Rohilkhand Medical College and
      Hospital of Northern India from June 2014 to May 2015. A total of 105 urine
      specimens from patients of BPH and/ or Prostatitis were cultured by a semi
      quantitative method. The isolated bacteria were identified by colony morphology,
      Gram's staining, motility and biochemical tests. Antibiotic sensitivity was done
      according to the CLSI 2007 guidelines by disc diffusion method. Data was analysed
      by SPSS and Microsoft office 2007. Proportions and percentages were used as
      statistical measures. RESULTS: The urine cultures from patients with BPH and or
      chronic Prostatitis, showed n=66/105 (62.85%) culture positivity. Out of 66
      isolates the frequency was in following order Escherichia coli 21/66 (31.81%),
      Klebsiella spp 19/66 (28.78%), Staphylococcus aureus 11/66 (16.66%), Pseudomonas
      aeruginosa (10.60%), Proteus spp, Enterococcus spp, Acinetobacter spp and
      Citrobacter spp. The most susceptible 1st, 2nd and 3rd line antibiotics for Gram
      negative isolates were ampicillin, amikacin and tigecycline respectively. Amongst
      the Gram positive isolates, the susceptible 1st, 2nd and 3rd line antibiotics
      were cefoxitin, vancomycin, teicoplanin and linezolid. Multidrug resistance was
      seen in Escherichia coli (n=6), Klebsiella spp (n=7), Pseudomonas aeruginosa
      (n=4) and Staphylococcus aureus (n=3). CONCLUSION: Based on the above findings we
      can say that accurate aetiology of the LUTS among the patients of BPH and/or
      Prostatitis is warranted to initiate the therapeutic management. Based on our
      study we state that the prime pathogens are E.coli, Klebsiella among Gram
      negative isolates and S. aureus among Gram positive. The most sensitive drugs are
      aminoglycosides, tetracyclines and carbepenems for Gram neagtive isolates and
      oxazolidinones and glycopeptides among Gram positive isolates.

PMID- 27891340
TI  - Dual Lower Respiratory Tract Infection by Burkholderia cepacia and Acinetobacter
      baumannii in A Neonate: A Case Report.
AB  - Burkholderia cepacia (B.cepacia) and Acinetobacter baumannii (A.baumannii), the
      highly intrinsically resistant nonfermenters are known to cause frequent
      infections in immunocomproimsed or hospitalized patients with significant
      mortality rate. In this rare clinical presentation, both were simultaneously
      isolated from a case of neonatal sepsis with respiratory failure. The prompt
      early diagnosis and antibiogram of these nonfermenters were proved to be of
      tremendous help in the present case with successful treatment outcome of dual
      infection of B.cepacia and A.baumannii. The present case report strongly
      emphasises the clinical importance of early accurate diagnosis of these emerging
      potential fatal non-fermenters which could otherwise prove fatal in case of any
      slight delay or misidentification. Implementation of strict surveillance policy
      to monitor the growth of these non-fermenters and draconian infection control
      measure holds a key to success in significant reduction of the associated
      mortality and morbidity.

PMID- 27891341
TI  - Clinicopathological Study of Surface Epithelial Tumours of the Ovary: An
      Institutional Study.
AB  - INTRODUCTION: It is an established fact that tumours of ovary inherit a spectrum
      of histogenetic background, the variety being more than any other organ. Surface
      epithelial stromal tumours of ovary being the most common type of ovarian tumours
      form a complicating and baffling subject in the history of oncology and hence,
      are an interesting topic for study. AIM: The aim of this study was to categorize
      the surface epithelial tumours of ovary into benign, borderline and malignant, to
      study their clinical and histopathological pattern and to compare their
      incidences with other studies. MATERIALS AND METHODS: This is a 5 year (3years of
      retrospective + 2 years of prospective) study conducted during the period of June
      2006 to May 2011. It consisted of 139 cases (141 tumours/ lesions). The relevant
      clinical details about the patient were retrieved from hospital data. RESULTS:
      The 141 surface epithelial tumours from 139 cases accounted for 66.2% of all the
      ovarian tumours encountered during the study period. The mean age of diagnosis in
      our study was 42.4 years. The most common clinical presentation was mass in
      abdomen. 90.6% of tumours were unilateral and 9.4% cases were bilateral. Right
      sided tumours (59.8%) were more common than left sided tumours (40.14%). 82.3%
      were benign tumours, 12.1% were malignant and 5.7% tumours belonged to the
      borderline category. CONCLUSION: Surface epithelial tumours present a great
      challenge to the gynecologic oncologist because non-neoplastic ovarian lesions
      can form a pelvic mass and potentially mimic a neoplasm. Their proper recognition
      and histopathologic classification is essential for appropriate management as
      malignant tumours are usually picked up at an advanced stage owing to their
      asymptomatic nature and inaccessible site for aspiration cytology and biopsy.
      Histopathological examination still remains the mainstay in diagnosis of these
      neoplasms.

PMID- 27891342
TI  - Immunohistochemical Evaluation of Role of Serotonin in Pathogenesis of Psoriasis.
AB  - INTRODUCTION: Psoriasis is a common skin disorder characterized by
      erythaematosquamous papules and plaques. It is known to be associated with
      stressful and depressive disorders. Serotonin is a neurotransmitter that plays a
      role in the pathogenesis of inflammatory skin disorders. AIM: To evaluate the
      role of serotonin in pathogenesis of psoriasis. MATERIALS AND METHODS: Using
      standard immunohistochemical techniques, 24 biopsies from patients with chronic
      plaque psoriasis were examined together with 12 biopsies from age and gender
      matched healthy subjects as a control group. RESULTS: Both the percentage of
      positive cells (p=0.018) and H-score values (p=0.015) of serotonin expression
      were significantly higher in psoriasis compared to normal skin. H score of
      serotonin expression was significantly higher in cases with totally absent
      Granular Cell Layer (GCL) as opposed to those with thin/focally absent GCL
      (p=0.011), and in cases with moderate/strong epidermal inflammation compared to
      cases with mild inflammation (p=0.035). No significant correlation was detected
      between H score of cases and age, disease duration or Psoriasis Area and Severity
      Index (PASI) score. CONCLUSION: Serotonin might play a role in development of
      psoriasis through its role as a growth factor promoting keratinocyte
      proliferation, and as mediator of inflammation and stimulant of T cell
      activation. It recruits T cells to sites of cutaneous inflammation and potentiate
      macrophage accessory function for T cell activation. Its expression is not
      related to the disease severity. Future large-scaled research on population of
      different ethnicities including other disease variants is needed. The use of
      serotonin receptor antagonists and serotonin reuptake inhibitors may be evaluated
      on wide-based studies to put the current observation into action.

PMID- 27891343
TI  - Expression of Alpha Methylacyl CoA Racemase (AMACR) in Gastric Adenocarcinoma and
      Its Correlation with Helicobacter pylori Infection.
AB  - INTRODUCTION: Gastric cancer develops in a multistep progression and is
      determined by genetic and environmental factors. Over-expression of Alpha
      Methylacyl CoA Racemase (AMACR) is useful in diagnosis of prostate cancer. There
      is plenty of genetic alteration that occurs in gastric adenocarcinoma. The
      present study was planned to determine if AMACR can be used as a diagnostic
      marker in gastric adenocarcinoma similar to prostate cancer. AIM: To study the
      expression of AMACR in gastric adenocarcinoma and correlate its expression with
      density of Helicobacter pylori. MATERIALS AND METHODS: This cross-sectional,
      prospective study was conducted from August 2013-2015. Fifty gastric cancer
      biopsies were taken. Adjacent biopsy from normal/reactive mucosa was also taken
      from 21 cases. Samples were stained with H&E for morphological details,
      Loeffler's methylene blue for Helicobacter pylori and immunohistochemistry (IHC)
      was done to check for the expression of AMACR proteins. Statistical analysis was
      done using chi square test, Spearman's correlation coefficient and Fisher's exact
      test. The p-value <= 0.05 was taken as critical level of significance. RESULTS:
      Overexpression of AMACR was observed in 88.89% of intestinal type and 78.05% of
      diffuse type adenocarcinoma. AMACR expression was significantly less in adjacent
      reactive/dysplastic mucosa. Helicobacter pylori were seen in 8/9 (88.89%) and
      35/41(85.36%) cases of intestinal adenocarcinoma and diffuse adenocarcinoma
      respectively. When grades of Helicobacter pylori were compared with the
      positivity of AMACR, no significant association and correlation was found.
      CONCLUSION: The expression of AMACR in neoplastic tissue was significantly higher
      as compared to adjacent dysplastic, reactive or normal tissue. Thus, IHC for
      AMACR can be used for differentiating the cases of reactive atypia from early
      neoplastic lesions similar to its role in prostatic tissue. Helicobacter pylori
      does not affect the expression of AMACR in neoplastic gastric lesions.

PMID- 27891344
TI  - Role of Scrape Cytology as an Adjunct to Fine Needle Aspiration Cytology in
      Diagnosis of Thyroid Lesions.
AB  - INTRODUCTION: Scrape cytology is an important diagnostic tool. It has been used
      in many tissue types as an adjunct or replacement for frozen section/ intra
      operative consultation. AIM: This study was done to evaluate the role of scrape
      cytology in the diagnosis of thyroid lesions, its role as an adjunct to Fine
      Needle Aspiration Cytology (FNAC) and application of this technique for intra
      operative consultation. MATERIALS AND METHODS: A prospective study on 50 thyroid
      neoplasms received over a period of 18 months (Nov 2014- March 2016) was
      conducted. Scrapings obtained from the fresh cut surface of thyroid specimens
      before formalin fixation, were smeared uniformly on to glass slides, and
      immediately fixed in 95% ethyl alcohol for rapid Haematoxylin and Eosin (H&E).
      Cytological findings were compared with pre-operative FNAC findings and
      histopathological diagnosis. Variables taken in to consideration while assessing
      the smears included cellularity, nuclear, cytological details and amount of
      colloid. RESULTS: There were total of 50 patients. Out of the 50 patients, 15
      were diagnosed as benign on scrape; of which 100% of cases were true negative for
      malignancy and five malignant cases were diagnosed as benign-false negative rate
      of 16.1%; four (8%) were deferred (non-diagnostic) with a true positive rate of
      83.3%. Histopathological correlation was available in all cases. The overall
      diagnostic accuracy of scrape cytology was 89.1% with sensitivity and specificity
      of 83.87% (C.I.; 66.27% to 94.55%) and 100% (C.I; 76.84% to 100.00%)
      respectively. Fine Needle Aspiration results were available in 41 cases of which
      2 were non-diagnostic. Of the remaining 39 cases 19 were benign and 20 were
      malignant with false negative rate of 40% and true positive rate of 60%. The
      overall diagnostic accuracy of FNAC was 64.1% with sensitivity and specificity of
      60% (C.I.; 40.6% to77.3 %) and 77.78% (C.I; 39.9% to 97.1%) respectively.
      CONCLUSION: We conclude that scrape cytology can act as a useful adjunct to FNAC
      and is a good procedure for intra-operative consultation. It is especially
      helpful in neoplasms diagnosed as suspicious for papillary carcinoma on
      aspiration and may obviate the need for a second procedure for completion
      thyroidectomy.

PMID- 27891346
TI  - Evaluation of Fluorescent Staining for Diagnosis of Leprosy and its Impact on
      Grading of the Disease: Comparison with Conventional Staining.
AB  - INTRODUCTION: Leprosy is a chronic infectious disease caused by Mycobacterium
      leprae (M. leprae). Histopathological examination of skin lesion is the gold
      standard for diagnosis. We evaluated the possible role of fluorescent microscopy
      in this direction which is increasingly used for rapid screening. AIM: To compare
      the efficacy of auramine rhodamine stain with Ziehl-Neelsen and modified Fite
      faraco staining in diagnosing M. leprae in tissue sections. STUDY DESIGN:
      Experimental, cross-sectional and retrospective study conducted for 4 years.
      METHODS AND MATERIALS: Skin biopsies of sixty clinically diagnosed leprosy
      patients were stained by Ziehl-Neelsen, Fite-Faraco and fluorescent stain. The
      presence of the bacilli and the bacillary index was scored for each case. The
      bacillary index by each staining methods were compared. STATISTICAL ANALYSIS:
      SPSS v 17 (IBM, New York) used for data analysis. Chi-Square test was used to
      calculate significance between differences. The p-value of <0.05 was considered
      as statistically significant. Pearson Correlation (r-value determined) was also
      used for comparison between groups. RESULTS: Sensitivity of fluorescent stain for
      indeterminate and borderline tuberculoid leprosies were 100% each. Positivity
      rates and mean bacteriological index with fluorescent stain was higher (43.3 and
      11.5 respectively) as compared to that of Ziehl- Neelsen and Fite-faraco when the
      bacillary load was less (bacillary index < 3). There was significant correlation
      between the three staining types at higher bacillary load. There was a higher
      mean bacillary index with fluorescent stain as well as detection of an additional
      multibacillary case. CONCLUSION: Fluorescent method is more sensitive than
      modified fite-faraco method in detecting lepra bacilli in tissue sections
      especially in cases with bacillary index less than three. With its higher
      sensitivity, paucibacillary cases could be upgraded to multibacillary thus
      affecting treatement decisions.

PMID- 27891345
TI  - Voluntary Blood Donation among Students - A Cross-Sectional Study on Knowledge
      and Practice vs. Attitude.
AB  - INTRODUCTION: The factors influencing blood donation decisions are varied and
      complex and one's attitude can influence this decision. AIM: To find the factors
      affecting the knowledge and practice of blood donation among college students and
      their attitude towards the same. MATERIALS AND METHODS: This cross-sectional
      study was conducted among 399 college going students using convenience sampling
      from medical, nursing and engineering colleges in Bhubaneswar city, where blood
      donation camps were to be held. Data was collected through self-administered
      questionnaires and, analysed in SPSS Version 20.0. RESULTS: Knowledge regarding
      blood donation was adequate among 228 (57.1%) of the students and, 221 (55.4%)
      students had donated blood. Knowledge was significantly better among female
      students, medical stream and in those whose parents were in non-medical jobs;
      whereas blood donation had been done significantly more by male, non-medical
      stream students and by those whose parents were in medical field. Most common
      reason for donating blood was a sense of social responsibility and most common
      reason of non-donation was fear of the procedure. An 85% of the students were of
      the view that they would donate blood if asked. Students suggested that small
      incentives like certificates and arranging transport for blood donation would
      make it easier to donate. CONCLUSION: Just over half of the students had adequate
      knowledge about blood donation and similar percentage had donated blood. There is
      this large pool of safe blood in college going students who are willing, but not
      tapped as source of blood donation.

PMID- 27891347
TI  - Decidual CD56+ Natural Killer Cells in Spontaneous Early Pregnancy Loss- An
      Immunohistochemical Study.
AB  - INTRODUCTION: Natural killer cells are believed to promote placental and
      trophoblastic growth and provide immune- modulation at maternal-fetal interface
      in pregnancy and their role in reproductive failure has been a matter of
      discussion. AIM: To study CD56+ Natural killer cells in spontaneous pregnancy
      loss. MATERIALS AND METHODS: In this prospective observational study, formalin
      fixed paraffin embedded sections from products of conception from twenty women
      each with spontaneous early pregnancy loss (test group) and elective pregnancy
      termination (control group). Immunohistochemical staining with CD 56 monoclonal
      antibody was done by avidin-biotin peroxidase technique. CD56+ cells in decidua
      were counted under light microscopy by two independent observers in ten high
      power fields (40X) and mean cell count taken. Student's paired 't'-test was used
      to statistically compare CD56+ NK cell population between the test and control
      groups. RESULTS: The mean number of CD56+ NK cells was higher in the decidual
      tissue of women who had spontaneous early pregnancy loss (mean+/-SD, 57.55+/
      1.79) as compared to the mean number of CD56+ NK cells in the decidual tissue
      from women who underwent elective termination (mean+/-SD, 50.9+/-3.46). The
      difference was statistically significant (difference of 6.65 with 95% confidence
      interval of 4.76 to 8.54, p-value <0.0001). CONCLUSION: This could imply that
      CD56+ NK cells have a role in the pathogenesis of spontaneous early pregnancy
      loss and further large scale studies can throw more light on the mechanism and
      designing of appropriate therapy.

PMID- 27891348
TI  - Composite Hemangioendothelioma: Report of a Rare Case.
AB  - Composite Hemangioendothelioma (CHE) is a new entity classified under the Heman
      gioendothelioma (HE) group of tumours. It is an extremely rare vascular neoplasm
      of low to moderate malignancy. Very few cases have been described in the
      literature. We herein report a case of CHE arising in a 31-year-old male who
      presented with a history of painless slow growing swelling on upper back since
      1year. Clinically, the surface of firm and mobile swelling of 1.5x1.5cm showed
      focal ulcerations. The histopathological findings were consistent with the
      diagnosis of composite hemangioendothelioma. The patient underwent wide local
      excision and at the end of five months of follow up there were no features of
      local recurrence or metastasis. To the best of our knowledge, this is the first
      reported case of CHE from India.

PMID- 27891349
TI  - Unusual Presentation of Acute Leukaemia: A Tripod of Cases.
AB  - Acute Leukemia is one of the common haematological malignancies encountered with
      varied clinical and haematological presentation. In acute leukaemia,
      complications like bleeding and infection cause significant morbidity and
      mortality, thus overshadowing the thromboembolic events. Among the various
      malignant haematological disorders, the association of thromboembolic events is
      often noted with acute promyelocytic leukemia, though the overall frequency of
      such events remains very low. Acute Lymphoblastic Leukemia (ALL) is, however,
      more common than Acute non-lymphoblastic Leukaemia. Usually patients present with
      symptoms because of cytopenias, organomegaly, lymphadenopathy and bone pain,
      including other skeletal abnormalities. Granular Acute lymphoblastic Leukaemia (G
      ALL) may be misdiagnosed as Acute Myeloid Leukemia (AML) because of the presence
      of cytoplasmic granules in the lymphoblasts. This variant of ALL is usually noted
      in children, but may be seen in adults too. It is also important to note that
      asymptomatic skeletal involvement can be seen in 40-60% of patients with ALL, but
      pathological fractures and osteolytic lesions along with hypercalcemia at the
      time of presentation are very rare. Herein, we present a series of three cases of
      acute Leukemia presenting with unusual clinical and other rare haematological
      findings.

PMID- 27891350
TI  - Hypersensitivity with Inhalational Budesonide: An Under Recognised Entity.
AB  - Hypersensitivity reactions are commonly encountered with drugs such as beta
      lactams, sulphonamides, allopurinol etc., Corticosteroids are frequently employed
      in the treatment of drug induced allergic reactions. Therefore, it is highly
      unlikely that a corticosteroid itself may cause such a reaction as an adverse
      effect. We had encountered a rare case of hypersensitivity reaction with
      inhalational budesonide in an eight-year-old boy. The patient developed
      maculopapular rashes over the back, buttocks and legs accompanied with pruritus
      within four hours of administration of the first dose. The reaction subsided
      within two days on withdrawal of the drug and treatment with oral fexofenadine.
      Re-introduction of budesonide by the same route after a month resulted in
      appearance of similar reaction. Both the parents of the patient were known cases
      of allergic rhinitis suggesting allergic pre-disposition in the family. Causality
      analysis using WHO-UMC scale suggested certain association of this allergic
      reaction with inhaled budesonide.

PMID- 27891351
TI  - Evaluation of Effect of Nishamalaki on STZ and HFHF Diet Induced Diabetic
      Neuropathy in Wistar Rats.
AB  - INTRODUCTION: Diabetic neuropathy is one of the most common complications
      affecting 50% of diabetic patients. Neuropathic pain is the most difficult types
      of pain to treat. There is no specific treatment for neuropathy. Nishamalaki
      (NA), combination of Curcuma longa and Emblica officinalis used to treat Diabetes
      Mellitus (DM). So, efforts were made to test whether NA is useful in prevention
      of diabetic neuropathy. AIM: To evaluate the effect of NA on diabetic neuropathy
      in type 2 diabetic wistar rats. MATERIALS AND METHODS: Group I (Control) vehicle
      treated consists of 6 rats. Diabetes induced in 36 wistar rats with
      Streptozotocin (STZ) (35mg/kg) intra-peritoneally followed by High Fat High
      Fructose diet. After confirmation of development of diabetes; rats divided into
      six groups (n=6). Group II - VII Diabetic Control, NA low dose, NA High dose,
      Glibenclamide, Pioglitazone and Epalrestat. Animals received drug treatment for
      next 12 weeks. Monitoring of Blood Sugar Level (BSL) done every 15 days and lipid
      profile at the end. Eddy's hot plate and tail immersion test performed to assess
      thermal hyperalgesia and cold allodynia. Walking function test performed to
      assess motor function. RESULTS: Diabetic rats exhibited significant (p<0.001)
      hyperalgesia and increased BSL compared to control rats. Dose-dependent
      improvement was observed in thermal hyperalgesia & cold allodynia in NA groups.
      Activity of NA was more than Glibenclamide, Epalrestat and Pioglitazone in high
      dose and comparable in low dose. Nishamalaki improved lipid profile. CONCLUSION:
      Apart from controlling hyperglycaemia and reducing lipid levels, NA effectively
      prevented the development of diabetic neuropathy.

PMID- 27891352
TI  - Herbal Fixed Dose Combinations in Nepal: Growing Concerns in a Developing
      Country.
AB  - Herbal medicines are mostly prepared as a combination therapy that has been used
      since therapeutic was first practiced. Combination products, also known as Fixed
      Dose Combinations (FDCs) of herbal remedies are in widespread use in Nepal.
      Herbal FDCs are in common practice because it is believed to have better
      adherence, less side effects and easy accessibility. Nevertheless, combination
      products possess greater risk of adverse effects, increases costs associated with
      treatments and leads to an ineffective dosages. Herbal FDCs are used extensively
      in Nepal although the rationality beyond the use of these combinations is still
      unidentified and at times are questionable. Legislations governing the use of
      herbal medicines is lacking in Nepal. Many herbal FDCs are not supported by any
      scientific data and test for the presence of ingredients mentioned in the package
      insert/container label is always difficult. A FDC of herbal products must be
      based on clear criteria that guarantee consumer safety and appropriate
      indications. These criteria helps to protect the consumers or patients from the
      misleading claims and risk associated with the use of unjustifiable combination
      of herbal substances. Strict monitoring from the regulatory body and the public
      awareness on the cost as well as advantages and disadvantages of herbal FDCs is
      urgently required.

PMID- 27891353
TI  - Association of C-Reactive Protein (rs1205) Gene Polymorphism with Susceptibility
      to Psoriasis in South Indian Tamils.
AB  - INTRODUCTION: Psoriasis is a multi-factorial heritable T-helper Th-1/Th-17
      mediated inflammatory disease, affecting the skin. It is associated with co
      morbidities such as Cardiovascular Disease (CVD). C-Reactive Protein (CRP) is a
      good inflammatory marker. CRP rs1205 polymorphism is associated with circulating
      plasma CRP levels. Although there is association between the rs1205 Single
      Nucleotide Polymorphism (SNP) and CVD, there are no prior reports regarding the
      association of CRP rs1205 SNP with psoriasis susceptibility. AIM: To study the
      association of the genetic variant rs1205 in the CRP gene with susceptibility to
      the disease and protein levels in South Indian Tamils with psoriasis. MATERIALS
      AND METHODS: In this case-control genetic study, 300 cases of psoriasis and 300
      age and gender matched controls were genotyped for CRP SNP rs1205 using Taq Man
      5'allele discrimination assay at Jawaharlal Institute of Postgraduate Medical
      Education and Research, Puducherry, India from February 2014 to January 2016.
      Plasma high sensitivity (hs)-CRP levels were estimated by ELISA. Disease severity
      was assessed by Psoriasis Area Severity Index (PASI). RESULTS: CRP genetic
      variation rs1205 was not associated with psoriasis risk in our South Indian Tamil
      population. However, the circulating levels of hs-CRP was significantly higher in
      patients with psoriasis, as compared with controls (p < 0.0001) and the protein
      levels were significantly associated with disease severity, as assessed by PASI
      scoring. No genotype was found significantly associated with PASI or CRP levels.
      CONCLUSION: Our results suggest that plasma CRP levels are higher in patients
      with psoriasis and correlate with disease severity, whilst CRP rs1205 is not
      associated with susceptibility to psoriasis in South Indian Tamils.

PMID- 27891354
TI  - Emerging Trends of Intentional Firearm Injuries in Northern India: A Study.
AB  - INTRODUCTION: Many developing countries are facing rise in firearm injury cases
      owing to communal and ethnic clashes, political violence, armed robberies and
      suicide causing huge economic loss to society. On the basis of intention,
      injuries can be categorized as intentional and unintentional or accidental
      injuries. Intentional injuries will include suicidal, homicidal and assault
      related injuries. AIM: This study was undertaken to document the trends and
      patterns associated with intentional firearm injuries in order to suggest ways to
      curb the emerging trends. MATERIALS AND METHODS: This was a cross-sectional and
      descriptive study conducted at Jawaharlal Nehru Medical College and Hospital
      (JNMCH), AMU, Aligarh, UP, India from May 2007 to April 2008. The parameters
      studied were month wise distribution of cases, age and sex distribution of
      victims of intentional gunshot injuries, body part injured, alleged assailant and
      medical management provided to the victim. The observed data was entered onto a
      worksheet and descriptive statistics were used. RESULTS: A total of 140 cases of
      intentional firearm injuries were studied, 133 were assault cases and 7 were
      suicide by means of firearm. Maximum number of intentional gunshot injury cases
      were reported during the month of September (17.14%) and October (14.29%) and
      least during month of December (2.14%). For intentional injuries, 21-40 years was
      the high risk age group (91 or 65% cases) with male preponderance (95.71%) and
      male to female ratio of 22:1. Preferred site for assault was the trunk, with
      50.38% cases with chest abdomen and back injuries. Family feud (20.71%) was the
      leading cause of assault and assailant was not known (47.86%) to the victim in
      majority of cases of assault injuries. CONCLUSION: Increasing cases of firearms
      as a means of assault and suicide, calls for limiting the number of handgun
      purchase, regulations to check illegal trade of firearms, accountability of
      ammunition used and to develop standardised hospital based data collection system
      so that trend and patterns associated with intentional firearm injuries can be
      determined.

PMID- 27891355
TI  - The Effect of Continuous Enteral Nutrition on Nutrition Indices, Compared to the
      Intermittent and Combination Enteral Nutrition in Traumatic Brain Injury
      Patients.
AB  - INTRODUCTION: Nutrition support is one of the most common care, which is
      undertaken for patients who suffered from Traumatic Brain Injury (TBI) and are
      admitted in intensive care units. Literature indicates some controversies
      regarding the appropriate method of nutrition support in these patients. AIM:
      This study was conducted for determining the effect of continuous enteral
      nutrition on nutrition indices, compared to the intermittent enteral and
      combination nutrition in TBI patients. MATERIALS AND METHODS: In a randomized
      clinical trial, 60 TBI patients who were admitted to critical care units of
      Taleghani Hospital of Kermanshah-Iran in 2010 recruited to the study. The samples
      were allocated to three groups of continuous enteral nutrition, intermittent
      enteral nutrition and combination nutrition supports by random sampling. The tool
      was a researcher-made checklist. The three methods of nutrition support were
      performed to the participants, then nutrition indices of patients were measured
      before and during three weeks. Data were analysed using SPSS software,
      descriptive, and inferential statistics. RESULTS: The mean of received energy in
      the combination group (53.1+/- 18.3%) was higher than continuous (38.5+/-19.7%)
      and intermittent (32.2+/-14.7%) groups, significantly (p<0.001). The received
      protein was also greater in combination method (67.7+/-16.9%) than continuous
      (31.8+/-15.1%) and intermittent groups (17.2+/-10.1%), (p=0.001). The mean of
      nitrogen balance was improved in continuous method from -4.7+/- -1.6 to 7.2+/
      5.2, (p<0.001) significantly. CONCLUSION: In this study, received energy of
      patients was not enough by three methods. However, the continuous method, having
      a positive effect on nitrogen balance, reducing hypercatabolism and maintaining
      the total body protein, was preferred to brain injury patients compared with
      intermittent enteral and parenteral methods that demand more studies.

PMID- 27891356
TI  - Attitudes and Perceptions of Medical Undergraduates Towards Mobile Learning (M
      learning).
AB  - INTRODUCTION: Mobile technology is one of the latest extensions of technological
      innovations that can be integrated into medical education. With the aid of these
      devices, students learn faster outside the classroom by having quick access to
      the internet and easy retrieval of required health related learning resources to
      keep alongside of recent trend and development. In medicine practice one has to
      continuously update his/her medical knowledge and mobile learning will serve as a
      tool for self-directed learning. AIM: To explore the attitudes and perceptions of
      undergraduate students towards M-learning. MATERIALS AND METHODS: This
      educational research included 90 third year MBBS students having clinical posting
      under the Department of Community Medicine from tertiary healthcare institute in
      Nashik. Students learning approach was studied with the help of pre-validated
      questionnaire to know whether they have deep or surface approach to learning. M
      learning group was formed on mobile social app to supplement conventional
      teaching-learning. One subject topic (Tuberculosis, Dengue fever/DHF,
      Hypertension and Diabetes Mellitus etc.) per week was allotted and after
      conventional teaching on first day of week the learning materials for the topic
      chosen for that week were uploaded on the group and students could download as
      well as share their ideas, learning resources, ask doubts and answer questions at
      least twice weekly through this mobile platform anytime, anywhere. At the end of
      three months students attitudes and perceptions towards M-learning were studied
      by pre-validated structured questionnaires. A five point Likert scale was used
      (5= strongly agree to 1= strongly disagree) for answering each item of all three
      questionnaires. The score of 60% (90 out of 150) and the score of 75% (30 out of
      40) for each item was considered as the measure that indicates whether or not the
      student had a positive attitude and perceived the importance of M-learning
      respectively. Utilisation of M-learning was also studied. RESULTS: It was found
      that 47 (52.2%) students had deep learning approach, 10 (11.1%) students had
      surface learning approach. An 80% of students had positive attitude towards M
      learning and 76.7% students had perceived the importance of M-learning. A 52.2%
      of students were actively involved in M-learning group for learning purpose. But
      57.8% students did not download (at least twice weekly) the shared reference
      material, 38.9% students never read and/or replied to the questions asked and
      60.0% students never asked any doubts/questions related to the discussion.
      CONCLUSION: Students had positive attitude and perceived the importance of M
      learning. But when they were provided with the opportunity, they did not show
      appreciable M-learning utilization. This could be because, M-learning was not
      implemented by all departments; also it was not the part of student's regular
      assessment and probably a lesser study duration.

PMID- 27891357
TI  - Effect of Integrated Approach of Yoga Therapy on Male Obesity and Psychological
      Parameters-A Randomised Controlled Trial.
AB  - INTRODUCTION: Obesity is a growing global epidemic and cause of non-communicable
      diseases. Yoga is one of the effective ways to reduce stress which is one of the
      causes of obesity. AIM: To assess the effect of Integrated Approach of Yoga
      Therapy (IAYT) yoga module on adult male obesity in an urban setting. MATERIALS
      AND METHODS: RCT (Randomized Controlled Trial) was conducted for 14 weeks on
      obese male subjects with yoga and control groups. Total number of subjects were
      72 and they were randomized into two groups (Yoga n=37, Control n=35). The
      subjects were from an urban setting of Mumbai and were doing yoga for the first
      time. Special yoga training of IAYT was given to yoga group for one and half hour
      for 5 days in a week for 14 weeks. The control group continued regular physical
      activities and no specific physical activity was given. The assessments were
      anthropometric parameters of weight, Body Mass Index (BMI), MAC (Mid Upper Arm
      Circumferences) of Left and Right Arm, Waist Circumference (WC), HC (Hip
      Circumference), WHR (Waist Hip Ratio), SKF(Skin Fold Thickness of Biceps,
      Triceps, Sub scapular, suprailiac and cumulative), Percentage body fat based on
      SKF and Psychological Questionnaires of Perceived Stress Scale (PSS) and AAQW
      (Acceptance and Action Questionnaire for Weight Related Difficulty). These were
      taken before and after intervention for both yoga and control groups. Within and
      between group analysis & correlation of differences from post to pre readings
      among the variables, were carried out using SPSS 21. RESULTS: The anthropometric
      and psychological parameters were improved in both the groups but changes were
      significant in yoga group. CONCLUSION: Incorporating the IAYT for obese male in
      urban setting will be effective for obesity treatment and for reducing the
      obesity related problems.

PMID- 27891358
TI  - The Effect of Stress Management Training through PRECEDE-PROCEED Model on
      Occupational Stress among Nurses and Midwives at Iran Hospital, Iranshahr.
AB  - INTRODUCTION: Occupational stress is a major factor in hindering the performance
      of nurses and midwives and developing physical and mental complications in them.
      Given that these two groups are in direct contact with patients more than other
      medical staff and stress management training can be effective in the reduction of
      occupational stress among the nurses and midwives. AIM: This study was set out to
      compare the effect of a PRECEDE-PROCEED based stress management training program
      on the occupational stress of the nurses and midwives. MATERIALS AND METHODS:
      This quasi-experimental study was conducted on the aforementioned nurses and
      midwives. Data collection instruments included the Nursing Stress Scale (NSS).
      The training program was held in two 4-hour-long sessions for three months from
      1st January to 31st March 2013. RESULTS: The results showed a significant
      increase in the PRECEDE scores of both groups by the end of the program, as
      compared to the baseline. A significant decrease was also observed in the stress
      scores of both groups. There was no difference between groups in these regards.
      CONCLUSION: The PRECEDE-based stress management training is effective in the
      reduction of occupational stress among the nurses and midwives.

PMID- 27891359
TI  - Diabetes Mellitus among Newly Diagnosed Tuberculosis Patients in Tribal Odisha:
      An Exploratory Study.
AB  - INTRODUCTION: The association between Diabetes Mellitus (DM) and Tuberculosis
      (TB) poses a strong public health challenge. Tribal ethnics possess a different
      propensity towards infectious and haematological diseases which may influence the
      inter-relationship of DM and TB and thus merit separate attention. AIM: To
      investigate the prevalence of diabetes in newly diagnosed pulmonary TB patients
      of tribal ethnicity in Odisha. MATERIALS AND METHODS: A cross-sectional study was
      carried out over a period of 9 months at four designated TB microscopic centres
      in a tribal district (Malkangiri) of Odisha. A total of 110 tribal adults newly
      diagnosed with pulmonary TB were examined for Fasting Blood Sugar (FBS) level.
      Diagnosis of DM and Impaired Fasting Glucose (IFG) were based on cut-off value of
      FBS recommended by the WHO. Data was entered and analysed using SPSS version
      22.0. RESULTS: The prevalence of diabetes and IFG are found to be 13.9% and 8.9%,
      respectively. A significant difference (p<0.05) was observed between the mean
      ages of the TB only (45.9 years) and TB-DM co-morbidity patients (53.8 years). No
      significant association was found between gender and diabetes. Clinical
      characteristics of TB were similar in TB and TB-DM co-morbidity patients.
      CONCLUSION: The prevalence of high FBS was found to be higher in newly diagnosed
      pulmonary TB patients of tribal ethnicity thus indicating the need for
      intensified bidirectional screening. Further studies should be undertaken towards
      the risk profiling of diabetes and other lifestyle diseases in this population.

PMID- 27891360
TI  - Why Should Viral Markers Be Mandatory in Ocular Surgeries: A Hospital Based
      Retrospective Study.
AB  - INTRODUCTION: Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) and Human
      Immunodeficiency Virus I, II (HIV-I,II) are serious global and public health
      problem. Knowledge of the seroprevalence would enable early diagnosis, treatment
      of patients and also help in prevention of horizontal spread of infection by
      application of universal infection control measures. AIM: To determine the
      seroprevalence of HBV, HCV and HIV I, II infection in patients undergoing ocular
      surgery. MATERIALS AND METHODS: A retrospective review of 560 patients who had
      undergone ocular surgery between Dec 2014 to June 2015 at Regional Institute of
      Ophthalmology, Patna, India, was done. Blood samples of patients were tested for
      the presence of Hepatitis B Surface Antigen (HBsAg) and anti-HCV antibodies by
      Enzyme Linked Immunosorbent Assay (ELISA) method, while HIV I, II was tested by
      ELISA and Western Blot as per National AIDS Control Organization (NACO), India
      guidelines. The number of patients with positive viral serology, age, sex ratio
      and nature of surgery were analysed. RESULTS: Out of 560 patients, 27 (4.8%)
      patients were found to be positive for viral serology. HBsAg was positive in 22
      patients (3.92%). Out of these 14 patients (2.5%) were male while 8(1.4%) were
      females. Anti- HCV was positive in 3 (0.53%) patients. Out of these 2(.35%) were
      male and 1 (.17%) was female. HIV was positive in 2 patients (0.35%), both of
      whom were males. CONCLUSION: Keeping in view the number of cases of
      seropositivity in our study and various studies showing the presence of these
      viruses in aqueous and tears, we suggest that screening for viral markers should
      be made mandatory before ocular surgery so that early detection and treatment of
      patients can be done and risk of horizontal spread is minimized.

PMID- 27891361
TI  - Serum FRAP Levels and Pre-eclampsia among Pregnant Women in a Rural Community of
      Northern India.
AB  - INTRODUCTION: There is a balance between the oxidative and the anti-oxidative
      forces in human body. Some studies document decreased level of anti-oxidant in
      pre-eclampsia while other studies showed normal level of anti-oxidant in pre
      eclampsia and the evidence is equivocal. AIM: The aim of the present study was to
      assess enzymatic anti-oxidant activities in pre-eclamptic women and compare it
      with normotensive pregnant women with period of gestation between 28 to 36 weeks.
      MATERIALS AND METHODS: A community-based cross-sectional survey was conducted
      (from November 2012-December 2013) at the Ballabgarh Health and Demographic
      Surveillance System (HDSS) site which was managed by Centre for Community
      Medicine, All India Institute of Medical Sciences, New Delhi, India. All
      registered pregnant women with period of gestation between 28 weeks - 36 weeks
      were eligible for inclusion in the study. All eligible pregnant women were
      contacted through home visit. A total of 217 pregnant women were enrolled out of
      which 209 blood samples were collected from pregnant women. About three ml of
      blood from antecubital vein was drawn without use of tourniquet, under aseptic
      conditions. It was later analysed for the serum anti-oxidative measures
      {Malanoaldehyde, Vitamin C, Ferric Reducing Ability of Plasma (FRAP) levels}.
      Data were entered on Epi-Info version 3.5.4. Data management and analysis was
      carried out in Stata 11. The means were compared using t-test and p-value stated.
      Categorical data was analysed using chi-square test. Logistic regression was used
      and adjusted p-value was stated. RESULTS: A total of 217 pregnant women were
      eligible for the study and all were enrolled. Out of the 217 blood samples
      collected, eight samples accidently got destroyed. A total of 28 out of remaining
      209 pregnant women (13.4%) had pre-eclampsia. Mean age (SD) was 22.4 (2.3) years,
      mean height (SD) was 156.6 (6.9) cm, mean weight (SD) was 65.1 (9.7) kg in pre
      eclampsia group. In pre-eclampsia group mean serum levels of malanoaldehyde,
      vitamin C and FRAP was 4.2 (0.26) ng/dl, 0.83 (0.11) mg/dl, 678.0 (35.6) MUmol/L.
      It was 4.5 (0.09) ng/dl,0.88 (0.03) mg/dl, 599.3 (13.3) MUmol/L in normotensive
      pregnant women group respectively. The difference was statistically significant
      for FRAP levels only. CONCLUSION: Serum anti-oxidant levels are not raised among
      women with pre-eclampsia.

PMID- 27891362
TI  - Health Seeking Behaviour among Tuberculosis Patients in India: A Systematic
      Review.
AB  - INTRODUCTION: The Revised National Tuberculosis Control Programme's (RNTCP)
      passive case finding approach strongly influence the health seeking behaviour of
      patients and the timing of health seeking as well. AIM: A systematic review was
      carried out to understand the health seeking behaviour, related delays and the
      knowledge and attitude regarding Tuberculosis (TB) and the health services linked
      with it. MATERIALS AND METHODS: A manual search strategy was adopted using PUBMED
      and Google Scholar search engines to obtain research papers in the said subject.
      Of 113 articles obtained by the end of this search process 10 full text articles
      were finally selected for the purpose of this review. RESULTS: Of the 10 studies
      identified, the results were delineated in 7 thematic areas such as: (1)
      Knowledge and perception of TB patients regarding TB and health services for TB;
      (2) Delays in seeking help; (3) Facility based health seeking behaviour; (4)
      Reasons for not seeking care/Delay in seeking care; (5) Geographical pattern
      (Rural-Urban) of health seeking; (6) Socio-cultural factors associated with
      health seeking; and (7) Gender based health seeking behaviour. CONCLUSION: Health
      seeking behaviour and related delays are of utmost importance in TB care from two
      important perspectives; firstly TB requires timely treatment and secondly it
      requires protracted treatment. Required level of knowledge and positive health
      behaviour helps the patients in taking timely help from appropriate health
      facility.

PMID- 27891363
TI  - Giant Cervical Osteophyte: An Unusual Cause of Dysphagia.
AB  - Dysphagia due to skeletal causes is a rare entity. A large cervical osteophyte
      can cause mechanical compression of the pharyngo-oesophageal segment leading to
      dysphagia. Large cervical osteophytes can occur in cervical spondylosis,
      ankylosing spondylitis or Diffuse Idiopathic Skeletal Hyperostosis (DISH). A 60
      year-old female came with progressive dysphagia due to a giant cervical
      osteophyte anterior to C4 and C5 vertebral bodies causing compression of the
      pharyngo-oesophageal segment. The patient was treated by surgical excision of the
      osteophyte by orthopaedic surgeons. The patient had complete relief of dysphagia
      following excision of the osteophyte.

PMID- 27891364
TI  - Desire of Bearing a Child took a Wrong Turn!!

PMID- 27891365
TI  - Visual Function and Ocular Status in Children with Disabilities in Special
      Schools of Northern India.
AB  - INTRODUCTION: Children with disabilities (other than visual impairment) are at a
      higher risk of visual impairment as compared to normal population. Majority of
      the ocular disorders, like refractive errors and strabismus, are easily
      treatable. As these children depend on their visual inputs for social and
      academic activities, an early detection and prompt treatment of even a minor
      visual problem is of utmost importance for them. AIM: To assess the visual
      function and ocular status of children with disabilities other than visual
      impairment and to identify the preventable and treatable causes of visual
      impairment. MATERIALS AND METHODS: The study was conducted on children aged 3-16
      years who were studying in special schools/ rehabilitation centers in Ludhiana.
      After prior permission, detailed ocular examination of all the children was done
      using standard examination techniques. Cycloplegic retinoscopy and refraction was
      also done and spectacles were prescribed. Children requiring further evaluation
      were referred to base hospital. RESULTS: A total of 404 children with
      disabilities (other than visual disabilities) studying in 7 rehabilitation
      centers/ special schools were enrolled. These included children with Cerebral
      palsy (12.1%), with Hearing impairment (35.3%), with Attention Deficit
      Hyperactive Disorder (ADHD) (3.7%), with Autism (8.6%), with Down syndrome
      (12.8%) and with Mental retardation (27.2%). Ocular disorders were seen in
      174(43%) children. The most common ocular disorders seen in these children were
      refractive errors (23%) and strabismus (18.1%). A total of 93(23%) children were
      prescribed spectacles and 37(9.2%) children were referred for further evaluation.
      CONCLUSION: Ocular problems are common in children with other disabilities. Delay
      in the detection and treatment of these disorders compounds the already existing
      disability in these children. Lack of awareness and sensitization among the
      parents and teachers is a matter of great concern. Therefore, strategies
      regarding increasing awareness, mandatory ocular examination in these children
      and early detection and treatment of the ocular disorders is the need of the
      hour.

PMID- 27891366
TI  - Evaluation of the Central Corneal Thickness with Anterior Segment Optical
      Coherence Tomogram after Penetrating Keratoplasty.
AB  - INTRODUCTION: Graft central thickness evaluates the graft quality which affects
      the outcome of Penetrating Keratoplasty (PK). It varies at different point of
      time after PK. Anterior Segment Optical Coherence Tomography (ASOCT) can measure
      graft's central thickness with quite high precision. AIM: The purpose of the
      study was to monitor the Central Corneal thickness (CCT) with ASOCT after PK and
      to evaluate its relationship with the pre-operative diagnosis. MATERIALS AND
      METHODS: This is an observational retrospective study where records of optical PK
      done in December 2012 and June 2015 were reviewed. Graft central thickness were
      analysed by ASOCT for all the patients post-operatively at first post-operative
      day, 3 and 6 months post PK by pachymetry scan and the images captured were
      analysed for CCT with inbuilt calipers. RESULTS: Fifty one eyes of 50 patients
      with age range of 17-80years (mean 51.64years +/-SD 18.45 years) with clear
      grafts were reviewed in the present study. All subjects recruited were analysed
      for the indications of PK. Adherent leucoma 20(39.21%) was most common indication
      for PK. Mean CCT were 647.31+/-90.40, 605.31+/-75.08,564.66+/-66.26 and 537.37+/
      64.09 respectively on first post-operative day, 1, 3 and 6 months. Graft CCT
      significantly decreased between first post-operative day and 1 month and it
      showed further decrease at 3 to 6 months post PK. The CCT at 6 month post-surgery
      showed a strongly positive correlation with the Intraocular Pressure (IOP)
      (r=0.66) and weakly positive correlation with Best Corrected Visual Acuity (BCVA)
      (r=0.28). CONCLUSION: Graft central thickness is considered to be quantitative
      method for evaluating corneal oedema post PK. CCT decreases in post-operative
      period irrespective of indications of PK.

PMID- 27891367
TI  - Comparison of Mustard Oil and Ghee Consumption on the History of Coronary Heart
      Disease in Urban Population of India.
AB  - INTRODUCTION: Coronary Heart Disease (CHD) is one of the leading causes of
      mortality in India, due to high consumption of mustard oil and ghee among urban
      population. AIM: To find out the relationship of mustard oil and ghee consumption
      on CHD history. MATERIALS AND METHODS: By a random cross-sectional, house-to
      house survey in North India, 137 people aged between 40-80 years (70 males and 67
      females) were selected by dietary history of Mustard Oil (MO) and Ghee
      consumption (G), but having no other CHD precipitating factor. Using food
      frequency questionnaire, the study population was divided into two groups based
      on the amount of MO and G consumption; Group A (n = 75): MO >1L/month, but G
      <0.5Kg/month and Group B (n = 62): MO =0.2 to 0.5L/month but G >1.25Kg/month.
      Serum lipid profile estimation and resting ECGs recording were done from all the
      subjects. RESULTS: There was no statistical significant difference in CHD history
      between the two groups. Mustard Oil had positive correlation with CHD history.
      CHD was higher by 50.9% in Group A and was independent of gender. However, the
      odds of CHD history were higher among males by 32.2% irrespective of the groups.
      CONCLUSION: The results demonstrated that CHD history was associated with higher
      relative consumption of mustard oil than ghee and CHD is positively correlated
      with increase mustard oil intake, blood level of TG, TC, LDL, VLDL, TC/HDL and
      LDL/HDL ratio.

PMID- 27891368
TI  - Is the Mean Platelet Volume a Predictive Marker of a Low Apgar Score and Insulin
      Resistance in Gestational Diabetes Mellitus? A Retrospective Case-Control Study.
AB  - INTRODUCTION: Gestational diabetes is defined as various degrees of glucose
      intolerance diagnosed or detected for the first time during pregnancy and is the
      most common metabolic complication of pregnancy. Early diagnosis and adequate
      treatment are important to prevent complications. Pre-eclampsia, polyhydramnios,
      fetalmacrosomia, and operative delivery are some of the complications seen in
      pregnant women diagnosed with Gestational Diabetes Mellitus (GDM). AIM: The
      present study was designed to determine whether there was an association between
      Mean Platelet Volume (MPV) in predicting poor fetal outcome, insulin resistance,
      neonatal Apgar scores and gestational age for women with GDM. MATERIALS AND
      METHODS: In this retrospective study, we enrolled 101 pregnant women with GDM
      together with a group of 138 healthy controls. MPV, insulin and homeostatic model
      assessment (HOMA-IR) values were measured at 24-28 weeks of the pregnancy. An
      independent samples t-test was used to compare MPV values. Multivariate linear
      regression models were used to establish relations between MPV values, HOMA-IR,
      insulin levels and Apgar score. RESULTS: There was a significant positive
      correlation between MPV values, HOMA-IR and Insulin levels and a negative
      correlation with Apgar score at 1 min and 5 min in the GDM group (r=0.227,
      p=0.02; r=0.206, p=0.03; r=-0.485, p<0.001; and r=-0.399, p<0.001, respectively).
      In the multivariate logistic regression analysis, a high MPV value was most
      consistently associated with a low Apgar 1 min score (beta=-0.387, p=0.003) in
      the GDM group. An MPV of >8.0 fL had a sensitivity of 82% and a specificity of
      75% for the prediction of GDM. CONCLUSION: We investigated the potential of MPV
      values in predicting low Apgar scores and insulin resistance in women with GDM.

PMID- 27891369
TI  - The Diagnostic Value of Urinalysis in Hemodialysis Patients with Fever, Sepsis or
      Suspected Urinary Tract Infection.
AB  - INTRODUCTION: The diagnostic validity of urinalysis in asymptomatic Hemodialysis
      (HD) patients is low and there is limited data on the diagnostic value of
      urinalysis in HD patients with fever, sepsis, or suspected Urinary Tract
      Infection (UTI). AIM: The aim of this study was to assess the sensitivity,
      specificity, positive and negative predictive value of pyuria, bacteriuria,
      Leukocyte Esterase (LE) and nitrite positivity in symptomatic, febrile or/and
      septic HD patients. MATERIALS AND METHODS: A single-center, retrospective study
      was performed at New York University Lutheran Medical Center, Brooklyn, New York
      City, USA, in order to investigate the diagnostic validity of pyuria,
      bacteriuria, LE and nitrite positivity in HD patients with admitting diagnosis of
      fever, sepsis or UTI from September 2008 to August 2015. RESULTS: A total of 275
      HD patients were included in the study. There was significant association between
      pyuria of different cut-offs (>5,>10,>50 WBC/HPF) and urine culture positivity
      (p<0.001) and growth of >=100,000 CFU/mL (p=0.039), but there was no association
      with fever or sepsis. The sensitivity and specificity of pyuria >10 WBC/HPF for
      positive urine culture with >100,000 CFU/mL was 86% and 35% respectively
      (p=0.025). Pyuria >50 WBC/HPF showed a sensitivity of 66% and a specificity of
      58% (p=0.032). There was also association between bacteriuria, LE positivity and
      positive urine cultures but not with >=100,000 CFU/mL. CONCLUSION: Our study
      results suggest that urinalysis is not a reliable diagnostic tool in febrile
      and/or septic HD patients and a urine culture is needed. In such patients,
      physicians should also maintain a high level of clinical suspicion for other
      potential sources of infection, which may not be initially evident.

PMID- 27891370
TI  - Trace Elements in Chronic Haemodialysis Patients and Healthy Individuals-A
      Comparative Study.
AB  - INTRODUCTION: End Stage Renal Disease (ESRD) patients despite receiving adequate
      Haemodialysis (HD) develop significant risk of Cardiovascular Disease (CVD).
      Abnormality in levels of trace elements may potentiate vascular injury by
      producing sustained inflammation and endothelial dysfunction. Hence, the present
      study was undertaken to evaluate the levels of trace elements in patients
      receiving HD. AIM: To study the blood levels of arsenic, cadmium, mercury, lead,
      chromium, barium, cobalt, caesium and selenium among ESRD patients undergoing HD
      and compare it with healthy individuals. MATERIALS AND METHODS: It was a cross
      sectional, comparative study done in a tertiary care center. About 40 established
      ESRD patients aged above 18 years, belonging to both sexes, undergoing chronic HD
      for more than six months were enrolled as Group A (Cases). Patients who had
      history of smoking and occupational exposure to heavy metals were excluded from
      the study. About 40 age and sex matched apparently healthy individuals attending
      health check-up were enrolled as Group B (Controls). Participants of this group
      had normal e-GFR by Modification of Diet in Renal Disease (MDRD) equation. About
      5ml of fasting venous blood sample was obtained from both groups and analyzed for
      trace elements. Chi-square/Fisher's-exact test was used for comparing ratios. A p
      value of <0.05 was considered statistically significant. RESULTS: In the present
      study, the mean blood levels of arsenic, cadmium, chromium and cobalt was found
      to be significantly higher in Group A as compared to Group B with all these
      parameters attaining a p-value of <0.001. Similarly, the mean blood levels of
      lead and caesium was high in Group A with a p-value of 0.001 each. The blood
      levels of mercury and barium did not vary significantly between both the groups
      with p=0.656 and 0.096 respectively. The blood levels of anti-oxidant selenium
      was lower in Group A, but did not attain statistical significance (p=0.217).
      CONCLUSION: The mean blood levels of toxic trace elements were significantly
      elevated with a simultaneous reduction in essential trace elements in patients
      receiving HD, which probably may contribute to an increase in CVD.

PMID- 27891371
TI  - Prediction of Post-operative Mortality in Patients with HCV-related Cirrhosis
      Undergoing Non-Hepatic Surgeries.
AB  - INTRODUCTION: Patients with chronic liver diseases are at great risk for both
      morbidity and mortality during the post-operative period due to the stress of
      surgery and the effects of general anaesthesia. AIM: The main aim of this study
      was to evaluate the value of Model for End-stage Liver Disease (MELD) score, as
      compared to Child-Turcotte-Pugh (CTP) score, for prediction of 30- day post
      operative mortality in Egyptian patients with liver cirrhosis undergoing non
      hepatic surgery under general anaesthesia. MATERIALS AND METHODS: A total of 60
      patients with Hepatitis C Virus (HCV) - related liver cirrhosis were included in
      this study. Sensitivity and specificity of MELD and CTP scores were evaluated for
      the prediction of post-operative mortality. A total of 20 patients who had no
      clinical, biochemical or radiological evidence of liver disease were included to
      serve as a control group. RESULTS: The highest sensitivity and specificity for
      detection of post-operative mortality was detected at a MELD score of 13.5. CTP
      score had a sensitivity of 75%, a specificity of 96.4%, and an overall accuracy
      of 95% for prediction of post-operative mortality. On the other side and at a cut
      off value of 13.5, MELD score had a sensitivity of 100%, a specificity of 64.0%,
      and an overall accuracy of 66.6% for prediction of post-operative mortality in
      patients with HCV- related liver cirrhosis. CONCLUSION: MELD score proved to be
      more sensitive but less specific than CTP score for prediction of post-operative
      mortality. CTP and MELD scores may be complementary rather than competitive in
      predicting post-operative mortality in patients with HCV- related liver
      cirrhosis.

PMID- 27891372
TI  - Experience with Splenic Abscess from Southern India.
AB  - INTRODUCTION: Splenic abscess is a rare entity with potentially life threatening
      complications. Sparse recent published data are available documenting the
      aetiological profile and management of patients with splenic abscess from India.
      AIM: To study the clinical profile of splenic abscess. MATERIALS AND METHODS: We
      retrospectively collected data from case records of admitted patients with
      splenic abscesses, to Nizam's Institute of Medical Sciences and Hospital which is
      a multispecialty, tertiary care referral hospital over a period of 15 months
      (from March 2014 to May 2015) and parameters studied were age, sex, symptoms,
      signs, risk factors, investigations like Ultrasound, CT scan, blood &
      microbiological culture, treatment and outcome. RESULTS: Most common presenting
      symptom was fever (90%). Mean age was 33.5 years. Five patients (55%) had risk
      factors like HIV, leukaemia and diabetes. From pus culture Escherichia coli was
      the most common organism (22%) grown. Staphylococcus saureus, Enterococcus
      faecium were seen in one each, blood culture grown Cryptococcus neoformans,
      Pseudomonas aeroginosa in one each, Plasmodium falciparum was seen on peripheral
      smear in one. Three were empirically treated as disseminated koch's. Another was
      treated as possible infective endocarditis. All were given antimicrobials, five
      (55%) were treated with antimicrobials alone, three (33%) with PCD (Per Cutaneous
      Drainage) and one (11%) with sub-total splenectomy. All patients recovered.
      CONCLUSION: With early diagnosis and increased use of ultrasound guided
      procedures like aspiration or drainage, spleenectomy can be avoided. Optimal
      treatment for splenic abscess is yet to be defined and customized to each
      patient.

PMID- 27891373
TI  - Retrospective Comparison of Clinical Characteristics and In-Hospital Outcomes
      among Diabetic and Non-Diabetic Adults with Acute Pyelonephritis.
AB  - INTRODUCTION: Acute Pyelonephritis (APN) is a common infection in community.
      Diabetes Mellitus (DM) may have different effect on clinical characteristics and
      outcomes of APN compared to non-diabetic individuals. AIM: To compare clinical
      characteristics and assess outcomes of APN patients with and without DM.
      MATERIALS AND METHODS: A retrospective analysis of 122 patients with DM (n=61)
      and without DM (n=61) was conducted at a single, private, urban set-up from
      Gujarat, India. Clinical symptoms, laboratory investigations, antibiotics
      treatment and outcomes in terms of mortality and prolonged hospitalization (10
      days and above) were compared in two groups. RESULTS: Mean age was significantly
      higher in diabetics than non-diabetics (55.2+/-12.5 vs 41.5+/-17.3, p<0.0001) and
      females were proportionally higher in both groups (65.6% Vs 62.3%, p=0.706).
      Fever was most frequent symptom (83.6% Vs 90.2%, p=0.283) followed by
      nausea/vomiting (50.8% Vs 63.9%, p=0.143), dysuria (66.7% Vs 74.4%, p=0.433) and
      flank pain (8.2 Vs 13.1, p=0.379). Backache/back pain (47.5% Vs 29.5%, p=0.041)
      and Chronic Kidney Disease (CKD) (63.9% Vs 45.9%, p=0.045) were significantly
      higher in diabetics than non-diabetics. Mean hospital stay did not vary
      significantly in two groups (7.0+/-3.2 Vs 6.50+/-2.9, p=0.346) but proportion of
      patients with longer hospital stay was higher in DM (16.4% Vs 8.2%). Elevated
      white cell count, erythrocyte sedimentation rate, C-reactive protein, serum
      creatinine and presence of red cell in urine (> 5/ high power field [hpf]) did
      not vary significantly in two groups. Cephalosporin-beta-lactamase inhibitor
      (Cefaperazone-Sulbactam/Cefepime-Tazobactam) was the most prescribed antibiotic
      in both the groups. No deaths were observed in any group during this evaluation
      period. Only raised ESR (>30 mm/hr) {Odds Ratio (OR): 1.58, 95% Confidence
      Interval (CI) 1.36-1.82, p=0.004} and presence of CKD (OR: 1.71, 95% CI 1.30
      2.25, p=0.008) were found to be the significant predictors of prolonged
      hospitalization in overall population. CONCLUSION: APN in diabetic and non
      diabetic patients has similar clinical characteristics. Impact of diabetes on
      clinical outcomes of mortality and prolonged hospitalization warrants further
      investigation in a large, randomized, prospective trial.

PMID- 27891374
TI  - Effect of Enhanced External Counter Pulsation Treatment on Aortic Blood Pressure,
      Arterial Stiffness and Ejection Fraction in Patients with Coronary Artery
      Disease.
AB  - INTRODUCTION: Enhanced External Counter Pulsation (EECP) is a non-invasive
      treatment option for patients with Coronary Artery Disease (CAD). The treatment
      has shown to augment diastolic pressure and reduce Left Ventricular (LV) after
      load by reducing systemic vascular resistance. The effect of EECP in standard
      brachial blood pressure and central haemodynamic parameters are not known. AIM:
      We hypothesized that EECP may have differential effect in CAD patients with low
      systolic blood pressure when compared to normal systolic pressure and the
      mechanism underlying this differential effect may be due to improvement in LV
      function. MATERIALS AND METHODS: A total of 72 consecutive patients who underwent
      EECP treatment for symptomatic CAD with LV dysfunction were divided into two
      groups based on cut-off value of 100mmHg for systolic blood pressure. First group
      had patients with brachial systolic blood pressure of >100mmHg and second group
      had patients with brachial systolic blood pressure of <=100mmHg. We measured
      central aortic systolic pressure, pulse pressure, augmentation index and
      augmentation pressure by SphygmoCor device and Ejection Fraction (EF) was
      measured by echo-cardiography. All these measurements were carried out prior to
      and after completion of 35 days of EECP sessions. RESULTS: Central systolic
      pressure, brachial systolic pressure, aortic pulse pressure, augmentation
      pressure and augmentation index significantly decreased in patients with normal
      brachial systolic pressure with baseline moderate LV dysfunction. Brachial
      systolic, aortic systolic and aortic pulse pressure significantly increased with
      no change in augmentation index and pressure is observed in patients with
      baseline severe LV dysfunction associated with low systolic pressure post EECP
      treatment. CONCLUSION: EECP treatment has haemodynamically favourable
      differential effect in normal and low brachial systolic pressure and this is
      mainly driven by improvement in LV function in patients with symptomatic CAD with
      LV dysfunction.

PMID- 27891375
TI  - Flow Mediated Dilatation, Carotid Intima Media Thickness, Ankle Brachial Pressure
      Index and Pulse Pressure in Young Male Post Myocardial Infarction Patients in
      India.
AB  - INTRODUCTION: Due to increase in Coronary Artery Disease (CAD) at a younger age,
      we should try to diagnose atherosclerotic process and population at risk, at the
      earliest. Flow Mediated Dilatation (FMD), Carotid Intima-Media Thickness (CIMT)
      and Ankle-Brachial Pressure Index (ABI) are probable markers for early
      atherosclerosis and may be useful in coronary risk stratification. AIM: To
      compare and correlate the FMD, CIMT, ABI and Pulse Pressure (PP) in young male
      patients of Myocardial Infarction (MI) with age and sex matched healthy controls.
      MATERIALS AND METHODS: Eighty male patients of MI aged <=45 years, who presented
      to the Cardiac Care Unit and Department of Medicine of Guru Teg Bahadur Hospital,
      Delhi, India, from November 2010 to April 2012 were recruited consecutively for
      this case control study and same number of age and sex matched healthy controls
      were also analyzed. Six weeks after MI, FMD of the brachial artery, intima media
      thickness of carotid artery, ABPI and PP were measured in the cases and compared
      with healthy controls. RESULTS: The FMD was lower among young patients of MI than
      controls (p<0.001). CIMT was higher among cases than controls (p=0.001). ABI was
      lower among cases than controls (p<0.001). Compared to controls, PP was higher
      among cases (p=0.001). In all subjects, a negative correlation between FMD and
      CIMT (r=-0.220, p=0.005) and a positive correlation between FMD and ABPI
      (r=0.304, p<0.001) was found. A statistically significant negative correlation
      was found between endothelial dependent FMD and PP among cases and control groups
      (r=-0.209, p=0.007). CONCLUSION: Biophysical parameters were deranged in young
      post MI patients. Majority of our young male patients fell in low risk Framingham
      risk score but still they manifested with CAD. Despite six weeks of treatment
      among young male patients of MI, various biophysical parameters were still
      deranged.

PMID- 27891376
TI  - Smokeless Tobacco and Stroke - A Clinico-epidemiological Follow-up Study in A
      Tertiary Care Hospital.
AB  - INTRODUCTION: Among the modifiable risk factors for stroke, tobacco smoking is
      well recognized. In some studies the use of Smokeless Tobacco (ST) has also been
      contributed as a risk factor for ischemic stroke. Use of ST is very common in
      South-East Asia. The form of ST varies according to the geographical and cultural
      variation. AIM: To study the various clinical symptoms and radiological findings
      of stroke due to different types of ST. MATERIALS AND METHODS: This was a
      prospective hospital based study carried out over a period of 2 years. All the
      cases within age group of 16 - 60 years and with a clinical and radiological
      diagnosis of acute stroke were included in the study. The Fagerstrom Test for
      Nicotine Dependence for ST of more than 6 was taken as the inclusion criteria.
      Patients having other addictions like smoked tobacco, alcohol, etc., and with
      important risk factors like hypertension, diabetes, dyslipidemia were excluded.
      The cases were extensively investigated and followed up for at least 6 months.
      Analysis was done using the Statistical Package for Social Sciences (SPSS-
      version 16.0). Descriptive statistics like percentage, mean were used wherever
      appropriate. RESULTS: During a period of 2 years, a total of 54 patients were
      studied. Forty two (77.7%) were males and 12(22.3%) were females. The mean age at
      presentation was 42.72(+/- 8.6) years and among all 96.3% patients were diagnosed
      as ischemic stroke. Among ST, pan was most commonly used in 21(38.9%) patients
      with an average of 14.6(+/-3.27) years of addiction. Hemiplegia was the
      predominant symptom on presentation (46, 85.2%). According to Oxfordshire Stroke
      Classification, partial anterior circulation infarct was most common in
      20(38.4%). The mean Modified Rankin scale after 5 days of hospital stay was
      3.83(+/-1.03) and after 6 months of follow-up was 2.1(+/-0.8). Patients were
      counseled for deaddiction and after 6 months follow-up 48(88.8%) patients had
      quit ST. CONCLUSION: ST is an important etiological factor for young ischemic
      stroke. This is the first study depicting clinical symptomatology of ST addicted
      ischemic stroke patients from India. Considering the increasing prevalence of ST
      use in south-east Asia, further long term studies are needed from this region.

PMID- 27891378
TI  - Isoniazid Induced Lupus Presenting as Oral Mucosal Ulcers with Pancytopenia.
AB  - Drug Induced Lupus Erythematous (DILE) is a rare adverse reaction to a large
      variety of drugs including Isoniazid (INH), with features resembling idiopathic
      Systemic Lupus Erythematosus (SLE). Diagnosis require identification of a
      temporal relationship between drug administered and symptom. It is an
      idiosyncratic reaction, with no pre-existing lupus. Our case highlights a rare
      presentation of isoniazid induced lupus with profound pancytopenia and mucosal
      ulcers, thus posing a diagnostic challenge. The patient was on multidrug
      treatment for pulmonary and knee joint tuberculosis. DILE was diagnosed on basis
      of strongly positive Anti Nuclear Antibodies (ANA), anti ds DNA and antihistone
      antibodies with clinical response to cessation of INH.

PMID- 27891377
TI  - Immune Thrombocytopenia as a Presenting Manifestation of Tuberculosis- Challenge
      in Resource Constraint Settings.
AB  - Tuberculosis can infect almost any organ of our body leading to various
      presentations and its complication. Various haematological manifestations of
      tuberculosis are well known. But isolated thrombocytopenia and Immune
      Thrombocytopenia (ITP) in patients with tuberculosis is very rare. Here we report
      a case of young man who presented with acute onset of bleeding manifestations in
      the form of epistaxis and macroscopic haematuria with platelets count of 5*109/L.
      The patient was diagnosed to have ITP along with clinical and radiological
      evidence of active tuberculosis. The patient was treated with Anti Tubercular
      Therapy (ATT) along with Intravenous (IV) pulse of methyl prednisolone followed
      by tapering dose of oral prednisolone.

PMID- 27891379
TI  - Rare Occurrence of Drug Induced Subacute Cutaneous Lupus Erythematosus with
      Leflunomide Therapy.
AB  - Leflunomide is an immunomodulatory drug exhibiting anti-inflammatory, anti
      proliferative and immunosuppressive effects. It has been widely used for
      treatment of active rheumatoid arthritis. Despite its good safety profile
      cutaneous side effects like alopecia, eczema, pruritis and dry skin have been
      reported with Leflunomide use. Skin ucleration, vasculitis, lichenoid drug rash
      and Subacute Cutaneous Lupus Erythematosus (SCLE) have been rarely reported with
      its use. A rare case of Leflunomide induced SCLE is being reported in a female
      patient with rheumatoid arthritis. The clinical features, histopathological and
      immunological characteristics were consistent with drug induced SCLE. Withdrawal
      of Leflunomide along with short course of topical steroids resulted in resolution
      of symptoms suggesting the drug to be the culprit. As this drug comes into
      widespread use, it remains to be seen whether more cases of DI-SCLE will occur/be
      reported. Fortunately, such a condition till times appears rare and is reversible
      once the drug is discontinued thus avoiding over evaluation and over treatment if
      the triggering drug is recognized.

PMID- 27891380
TI  - Is Transoesophageal Echocardiography Necessary for the Percutaneous Management of
      Lutembacher Syndrome: A Case Report.
AB  - Lutembacher syndrome is defined as a combination of congenital Atrial Septal
      Defect (ASD) with an acquired Mitral Stenosis (MS). There are various challenges
      involved in the percutaneous management of Lutembacher syndrome. Here, we present
      a case that had a very small Left Atrium (LA) and Left Ventricle (LV) cavities
      with an anteriorly placed ASD. We used Transoesophageal echocardiography (TEE) to
      take a separate interatrial septal puncture and complete the Balloon Mitral
      Valvotomy (BMV) procedure. Finally both the defects in interatrial septum were
      closed with the help of a large device.

PMID- 27891381
TI  - Post Colonoscopy Ischaemic Colitis in a Patient without Risk Factors for Colon
      Ischemia: A Case Report.
AB  - Ischaemic colitis is the most common form of intestinal ischaemia and is more
      common in the elderly and in the people having risk factors for colonic
      ischaemia. Colonoscopy procedure itself is a rare cause of ischaemic colitis.
      Fewer than 20 cases of ischaemic colitis caused by colonoscopy procedure have
      been reported in the english literature till date. This patient presented to us
      within hours of routine colonoscopy with rectal bleeding and lower abdominal
      pain. On repeat colonoscopy, the patient had mucosal oedema and ulcerations in
      the descending colon and sigmoid colon. Computed tomography of abdomen and biopsy
      of the involved segment confirmed ischaemic colitis. The patient recovered with
      conservative management.

PMID- 27891382
TI  - A Case of Immune Thrombocytopenic Purpura Secondary to Pulmonary Tuberculosis.
AB  - The haematological abnormalities associated with active pulmonary tuberculosis
      were known to human beings since decades but Immune Thrombocytopenic Purpura
      (ITP) secondary to pulmonary tuberculosis have been reported only in a couple of
      instances. We report a 27 year-old male patient who was admitted to our hospital
      with fever, shortness of breath, haematuria, epistaxis and generalized petechiae.
      The sputum positivity for Acid Fast Bacilli (AFB) and chest X-ray reports were
      suggestive of active pulmonary tuberculosis in our patient. Clinical and
      laboratory parameters including bone marrow aspiration cytology diagnosed the
      case to be ITP. Patient was put on Directly Observed Treatment and Short course
      (DOTS) category-1 Anti-Tuberculosis Therapy (ATT) and prednisone following which
      thrombocytopenia was corrected and there was complete recovery of the patient
      without recurrence of thrombocytopenia.

PMID- 27891383
TI  - Ruptured Sinus of Valsalva with Infective Endocarditis Complicated with Post
      Infectious Acute Glomerulonephritis: A Rare Case Presentation.
AB  - Ruptured Sinus of Valsalva (RSOV) is a rarely seen disease condition. RSOV can
      have varied presentations from being asymptomatic with just a cardiac murmur to
      profound hypotension. There has been simultaneous occurrence of RSOV with
      Infective Endocarditis (IE) in literature. Glomerulonephritis has also been
      reported in approximately 20% patients with IE. Large amount of proteinuria or
      decline in kidney functions is rarely encountered and mostly this finding has
      been incidental on routine evaluation. The co-existence of all the three
      conditions in a single patient is rare. This case was diagnosed to have RSOV with
      IE and was also diagnosed with post-infectious glomerulonephritis on renal
      biopsy. Patient was advised corrective cardiac surgery, but due to financial
      constraints, patient could not be operated and he died. Here, we report for the
      first time an unusual presence of both RSOV and sub-aortic membrane with IE
      complicated by glomerulonephritis.

PMID- 27891384
TI  - Bioresorbable Scaffolds: Current Evidences in the Treatment of Coronary Artery
      Disease.
AB  - Percutaneous coronary revascularization strategies have gradually progressed over
      a period of last few decades. The advent of newer generation drug-eluting stents
      has significantly improved the outcomes of Percutaneous Coronary Intervention
      (PCI) by substantially reducing in-stent restenosis and stent thrombosis.
      However, vascular inflammation, restenosis, thrombosis, and neoatherosclerosis
      due to the permanent presence of a metallic foreign body within the artery limit
      their usage in complex Coronary Artery Disease (CAD). Bioresorbable Scaffolds
      (BRS) represent a novel approach in coronary stent technology. Complete
      resorption of the scaffold liberates the treated vessel from its cage and
      restores pulsatility, cyclical strain, physiological shear stress, and
      mechanotransduction. In this review article, we describe the advances in this
      rapidly evolving technology, present the evidence from the pre-clinical and
      clinical evaluation of these devices, and provide an overview of the ongoing
      clinical trials that were designed to examine the effectiveness of BRS in the
      clinical setting.

PMID- 27891385
TI  - When Pulmonary Function Test is Available, Should we Wait for the COPD Symptoms
      to Develop?
AB  - Adolescent smokers are more likely to be addicted to nicotine and develop a
      chronic habit. Chronic smoking has a direct impact on quality of life and life
      expectancy. Repeated environmental exposure and smoke inhalation can be
      deleterious to health. In order to evaluate the core functioning of the lungs,
      Pulmonary Function Tests (PFTs) are conducted. This panel of tests should be
      advised for all patients complaining of shortness of breath. Since clinical
      features resulting from chronic smoking tend to appear late in the course of the
      disease, PFTs are immensely useful for early identification of abnormalities in
      asymptomatic adult smokers. Numerous studies have shown that normal PFT
      parameters begin to deteriorate immediately after smoking is initiated. However,
      most physicians prefer to wait for characteristic signs and symptoms of Chronic
      Obstructive Pulmonary Disease (COPD) to develop before proceeding with PFTs in
      the patients. This leads to inadvertent and often dangerous delay in reaching a
      definitive diagnosis and initiating treatment. Therefore, we undertook this
      review to determine whether conducting PFTs in asymptomatic adult smokers can
      facilitate the early detection and/or prevention of COPD. We reviewed and
      analyzed articles from PubMed, Google Scholar, Index Medicus, WHO Global Health
      Library and Scopus, which specifically demonstrated the presence of abnormal PFT
      changes in asymptomatic adult smokers. With PFTs, we now have the advantage of
      diagnosing early changes in the lung volumes. Hence, we conclude that PFTs should
      be performed early in smokers and cessation of smoking should be encouraged to
      check the increasing incidence of COPD.

PMID- 27891386
TI  - A Case of Interosseous Membrane Calcification.

PMID- 27891387
TI  - Continuous Ambulatory Peritoneal Dialysis Catheter Tunnel Breakdown and its
      Repair.

PMID- 27891388
TI  - Desmoid Tumours in Familial Adenomatous Polyposis: Review of 17 Patients from a
      Portuguese Tertiary Center.
AB  - INTRODUCTION: Desmoid Tumours (DT) are benign tumours with an estimated incidence
      of 2-4 per million per year. Between 7-16% of them are associated with Familial
      Adenomatous Polyposis (FAP) and are mostly parietal or intra-abdominal. They are
      a challenge in relation to their unpredictable natural course, associated
      complications and difficult treatment. AIM: The aim of the present study was to
      review the occurrence, management and follow-up of DT on FAP patients treated
      consecutively at a tertiary care center. MATERIALS AND METHODS: A retrospective
      review of clinical data from patients treated consecutively between 1993 and
      2014. Patients' data was gathered from clinical records. Data collection included
      the following variables: demographic data, genotype, FAP phenotype, data on FAP
      related surgery, DT diagnosis, location, size and number, DT treatment, patients'
      status and follow-up data. RESULTS: The study population consisted of 17 patients
      from 9 families; with a mean age of 41 years, mostly women (59%) and most with a
      mutation either on codon 232 or 554. Most tumours had an intra-abdominal
      component (59%) with a mean size of 5cm. Fifteen patients were first treated with
      pharmacotherapy (Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Tamoxifen).
      Five patients (29%) underwent surgery, 4 of them for complications of intra
      abdominal tumours and 1 patient for abdominal wall tumours. Two patients
      underwent chemotherapy in relation to aggressive intra-abdominal disease. The
      mean follow-up time since diagnosis of DT was 123 months. Overall, 2 patients had
      remission, 11 patients had regression or stabilized disease, and 2 patients had
      progression. One patient died due to surgical complications. CONCLUSION:
      Diagnosis of DT is based on clinical symptoms, without the need for screening,
      although imaging plays an important role once diagnosis is suspected. The
      treatment approach is conservative on most patients, leaving surgery for DT
      related complications. The follow-up of patients with DT is also based on
      clinical symptoms.

PMID- 27891389
TI  - A Comparative Study of Single Incision versus Conventional Four Ports
      Laparoscopic Cholecystectomy.
AB  - INTRODUCTION: Cholelithiasis is one of the most common disorders of the digestive
      tract encountered by general surgeons worldwide. Conventional or open
      cholecystectomy was the mainstay of treatment for a long time for this disease.
      In the 1980s laparoscopic surgery revolutionized the management of biliary tract
      diseases. It brought about a revolutionary change in the basic concepts of
      surgical principles and minimal access surgery gradually started to be
      acknowledged as a safe means of carrying out surgeries. AIM: To investigate the
      technical feasibility, safety and benefit of Single Incision Laparoscopic
      Cholecystectomy (SILC) versus Conventional Four Port Laparoscopic Cholecystectomy
      (C4PLC). MATERIALS AND METHODS: This prospective randomized control trial was
      conducted to compare the advantages if any between the SILC and C4PLC. Thirty two
      patients underwent SILC procedure and C4PLC, each. The age of the patients ranged
      from 16-60years. Other demographic data and indications for cholecystectomy were
      comparable in both the groups. Simple comparative statistical analysis was
      carried out in the present study. Results on continuous variables are shown in
      Mean +/- SD; whereas results on categorical variables are shown in percentage (%)
      by keeping the level of significance at 5%. Intergroup analysis of the various
      study parameters was done by using Fisher exact test. SPSS version 22 was used
      for statistical analysis. RESULTS: The mean operating time was higher in the SILC
      group (69 +/- 4.00 mins vs. 38.53 +/- 4.00 mins) which was of statistical
      significance (p=<0.05). Furthermore, the patients of the SILC group had less post
      operative pain, with lesser analgesic requirements (p=<0.05), shorter hospital
      stay and earlier return to normal activity. CONCLUSION: SILC is feasible and safe
      in trained hands. It did not compromise the procedural safety, or lead to any
      complication. The operating time was longer otherwise it has almost similar
      clinical outcomes to those of C4PLC.

PMID- 27891390
TI  - Effectiveness of Centchroman on Regression of Fibroadenosis and Mastalgia.
AB  - INTRODUCTION: Fibroadenosis and mastalgia are common among the women in
      reproductive age group. Treatment for these conditions is not yet standardised.
      Most of the drugs used for fibroadenosis and mastalgia are expensive and have
      side effects. AIM: To find out the efficacy of centchroman, a Selective Estrogens
      Receptor Modulator (SERM) on regression of fibroadenosis and mastalgia. MATERIALS
      AND METHODS: Fifty one patients with mastalgia/fibroadenosis were treated with
      centchroman 30mg once daily on alternate days for a period of 3 months and
      followed up weekly for six months with Mastalgia chart and Visual Analog Scale
      (VAS) pain score. RESULTS: Before starting treatment, four patients presented
      with pain score of 6 followed by, 37 patients with a score of 4 and 10 patients
      with a score of 2. All the patients were started on tab centchroman 30mg OD
      alternate days and were reviewed on weekly basis with Mastalgia chart and VAS
      pain score for three months. On fifth and sixth visit, 46 patients reported with
      pain score 0, one with pain score of 2 and four with pain score of 6. The
      efficacy of centchroman was found to be significant (p-value = 0.001). Three
      patients (5.9%) reported epigastric pain and ten patients (19.6%) reported
      menstrual delay. A total of 38 patients did not complain of any side effect.
      CONCLUSION: Our study proves that centchroman is a safe and cost effective drug
      with significant efficacy on regression of fibroadenosis and mastalgia with
      minimal side effect.

PMID- 27891391
TI  - Identification and Cost of Disposable Endourological Devices for Nephrolithiasis:
      A Cross-Sectional Study Among Urological Trainees.
AB  - INTRODUCTION: Knowledge on health economics among urology trainees is not
      formally assessed. The cost of commonly utilised endourological devices may not
      be considered by trainees. AIM: The present study was conducted with the aim to
      assess whether urology trainees were knowledgeable on identification and cost of
      commonly used disposable devices in the management of nephrolithiasis. MATERIALS
      AND METHODS: Forty urology trainees in Ireland were invited to complete a visual
      online questionnaire on the identification of 10 frequently utilised disposable
      endourological devices. In addition, trainees were requested to estimate the cost
      of 12 disposable endourological devices. Responses were stratified according to
      trainee grade and urological subspecialty of interest. Data are presented as a
      mean +/- standard deviation. RESULTS: The response rate was 70% (28/40).
      Endourology was the subspecialty of interest in 21% (n= 6). No trainee correctly
      identified all 10 endourological devices and the mean test score was 5.32 +/-
      2.28. No trainee accurately estimated the cost for all 12 devices assessed. The
      cost of endourological devices was underestimated by ?67.13 +/- ?60.76 per
      device. A total of 54% (n=15) of trainees underestimated the total cost of
      disposable devices used during standard flexible ureterorenoscopy, laser
      lithotripsy and JJ stent insertion by ?303.66 +/- ?113.83. CONCLUSION: Our
      findings indicate deficiencies in trainee knowledge on endourological devices and
      their associated costs. Incorporating a health economics module into postgraduate
      urology training may familiarise trainees with healthcare expenditure within
      their departments.

PMID- 27891392
TI  - A Study of Evaluation and Management of Rare Congenital Breast Diseases.
AB  - INTRODUCTION: Polymastia and polythelia may be asymptomatic or cause pain,
      restriction of arm movement, milk discharge, cosmetic problems or anxiety.
      Cosmesis is the main indication for surgical excision of accessory breasts in
      axilla. In addition it also confirms the diagnosis and allays the patient's fear
      of harbouring a malignancy. AIM: To evaluate the presentation of symptoms,
      investigations required for diagnosis and the management to improve the treatment
      protocols in patients with breast diseases. MATERIALS AND METHODS: This
      retrospective study on breast diseases presenting as supernumerary breasts and
      nipples was conducted in the Department of Surgery between January 2013 and
      January 2016 at MMIMS Research and hospital, Mullana, Ambala. Patients were
      evaluated for breast diseases, either benign or malignant in both genders. A
      total of 32 cases diagnosed as accessory breasts disease were retrieved from the
      hospital archive. The clinical and radiological evaluation was done in the form
      of ultrasound and mammography wherever necessary. Accessory breast tissues were
      excised under general anesthesia and histopathological examinations were done.
      RESULTS: Out of 32 cases: 1(3.125%) male patient had unilateral and 1(3.125%)
      male had bilateral accessory nipple, 7 (21.87%) females had unilateral and
      1(3.125%) had bilateral accessory nipple, 1 (3.125%) diagnosed as accessory
      axillary fibroadenoma in female, 16(50%) presented as unilateral and 5 (15.62%)
      had bilateral swelling in the axilla as accessory breast. Patients underwent
      surgical excision and in 8(25%) cases z- shaped incision was made in view of
      better cosmesis. Patients were followed up upto 6 months postoperatively. There
      were no residual swelling and movements of the arm over the shoulder joint were
      normal. In 3(9.37%) cases, wound dehiscence occurred; in 2 (6.25%) cases
      lymphoedema formation was seen. These were successfully managed conservatively.
      CONCLUSION: As breast swellings either fibroadenoma or carcinoma are common
      entities to come across everywhere but accessory breasts are rarely encountered
      especially in rural areas because of less awareness. The study found that there
      was tendency to neglect the swelling as there were minimal symptoms present. We
      also came across a rare entity, accessory breast and accessory nipples. A
      clinician should not ignore such cases taking as simple swelling because of
      chances of discovering a malignancy can occur.

PMID- 27891393
TI  - Day Care vs Overnight Stay after Laparoscopic Cholecystectomy even with Co
      morbidity and a Possible Second Surgery: A Patient's Choice.
AB  - INTRODUCTION: Laparoscopic Cholecystectomy (LC) has become the gold standard for
      symptomatic gall stone disease. It is being practiced as a day care procedure in
      healthy individuals in American Society of Anaesthesialogists (ASA) grade I and
      II. It is not yet established in presence of co-morbidity and when a second
      surgery is added. In most of the study, patient's choice and the psycho-social
      factors were not considered in deciding the day care procedure. AIM: To find the
      safety of LC and a second surgery as day care in presence of compensated co
      morbidity. To study the choice of the patient whether to stay in hospital or go
      home after declaring them fit for day care. MATERIALS AND METHODS: All the
      patients of symptomatic cholelithiasis with co-morbidity and associations were
      evaluated and made uncompromising for elective surgery. All the LC were done at
      8mmHg CO2 peumo-peritoneal pressure using harmonic scalpel as the energy source
      for dissection of gall bladder from the liver bed. Cases with conversion and
      placement of drain were excluded. RESULTS: A total of 1029 out of 1042 patients
      was included from Jan 2005 to Jan 2015. The age range was 38 to 91years (mean
      44.65, SD 14.15). There were 634 females and 395 males. A total of 121(11.7%) of
      them had co-morbidity and associations. A total of 72(7%) had undergone a second
      surgery. Only 0.8% had real day care. A total of 95.7% had overnight stay even
      after fulfilling all the criteria. Only 0.2% needed re-admission in 30 days and
      one required intervention. CONCLUSION: Patients like to stay over night in the
      hospital even if found fit for day care after LC. Overnight stay makes them
      happy, psycho-socially confident in developing nation and best suited for all
      patients including co-morbidity.

PMID- 27891394
TI  - Obesity Not Necessary, Risk of Symptomatic Cholelithiasis Increases as a Function
      of BMI.
AB  - INTRODUCTION: Obesity is a well-established risk factor for cholelithiasis. But
      most of the studies have actually tried to establish the risk of cholelithiasis
      in overweight and obese people. Very few studies have addressed the issue of
      cholelithiasis in patients with otherwise normal Body Mass Index (BMI). In this
      study we have tried to establish if there is any relationship between increasing
      BMI and cholelithiasis. AIM: To establish a relationship between increasing BMI
      and risk of cholelithiasis. MATERIALS AND METHODS: Retrospective analysis was
      carried out after doing a prospective pilot study. Ten years data of patients
      admitted to surgery ward with complaints of pain abdomen was reviewed. Patients
      with cholelithiasis were segregated as cases and patients with some other
      diagnosis were selected as controls. Patients with incidental diagnosis of
      cholelithiasis were excluded. Appropriate analytical tools were used to draw the
      results using SPSS(c) 20. RESULTS: Over 11,000 patients data was reviewed and
      7,182 patients were selected for inclusion into the study. Major exclusion was
      due to incomplete availability of data. Cholelithiasis group had 2,872 patients
      and rest of the patients served as controls against them. Female patients
      outnumbered their male counterparts in cholelithiasis group. Mean age of the
      gallstone patients was 37.09 years, almost 2 years younger than their controls.
      Mean BMI of all patients was 23.55 kg/m2 and in cholelithiasis and control group
      was 24.93 and 22.62, respectively (df=1, F>1635.395, p<0.001). Gender specific
      comparison also yielded a significant difference df=3, F=547.238, p<0.001). The
      difference in the way the patients were distributed among the ethnic groups
      (Nepalis, Bhutias, Lepchas and others) was also significant (df=3, F=34.234,
      p<0.001). Most important outcome was that the majority of the patients in the
      cholelithiasis group were within the normal BMI range. CONCLUSION: We concluded
      that it's not only the overweight or obese patients who develop symptomatic
      cholelithiasis but also the individuals with normal BMI. The risk of symptomatic
      cholelithiasis increases with every increase in BMI. Risk of symptomatic
      cholelithiasis also increases in women and as the age advances.

PMID- 27891395
TI  - Bellini Duct Carcinoma: A Rare Entity.
AB  - Bellini duct carcinoma of kidney derives from collecting duct and is associated
      with an aggressive course and extremely poor prognosis. Here, we report an
      interesting case of Collecting Duct Carcinoma (CDC) with Inferior Vena Cava (IVC)
      thrombus and large retroperitoneal lymph nodes and diffuse desmoplastic reaction.
      The patient underwent left open radical nephrectomy with IVC thrombectomy and
      regional lymphadenectomy. Based on morphological and immunohistochemical
      analysis, diagnosis of collecting duct (Bellini duct) carcinoma was made.
      Presently, patient is on adjuvant chemotherapy with gemcitabine and cisplatin and
      under follow-up.

PMID- 27891396
TI  - Endoscopic Excision of Symptomatic Simple Bone Cyst at Skull Base.
AB  - Seizure is a classical feature of intra axial brain parenchymal lesion. Simple
      bone cyst is an unusual bony pathology at skull base presenting with unexpected
      symptoms of complex partial seizures. Skull base neuro-endoscopy has managed such
      lesions more effectively with reduced post-operative morbidity as compared to
      transcranial approach. This case report discusses a 20-year-old male who
      presented with 3 episodes of seizure over a time period of 10 months. MRI brain
      revealed T1 hypo and T2 hyper intense cystic lesion in middle cranial fossa with
      no enhancement on contrast administration. CT scan showed cystic lesion involving
      greater wing and pterygoid plate of sphenoid on left side. CT cisternographic
      evaluation showed CSF outpouching in the sphenoid air sinus. Excision of the
      cystic lesion was carried out through endoscopic transmaxillary transpterygoid
      approach. Histopathological examination showed the lesion to be a simple bone
      cyst.

PMID- 27891397
TI  - Spontaneous Subdural Haematoma Developing Secondary to Arachnoid Cyst Rupture.
AB  - Arachnoid cysts are congenital, benign, non-neoplastic, extra-axial intra
      arachnoidal lesions. Arachnoid cysts rarely become symptomatic, with bleeding.
      Intracranial haemorrhage as a complication of arachnoid cyst is a very rare
      condition. It is well-known that mid-cranial fossa cysts might cause
      intracerebral haemorrhage or subdural haematoma secondary to traumas. However,
      the occurrence of spontaneous subdural haematoma secondary to arachnoid cysts,
      developing without any trauma, is even rarer. A 17-year-old boy presenting with
      diplopia and headache, with no history of trauma, was diagnosed with left
      temporal lobe arachnoid cyst and left fronto-parietal subdural haematoma. He was
      operated on, solely for his haematoma, with no intervention performed for the
      arachnoid cyst. Authors suggest that it is sufficient to perform an operation for
      the haematoma only -without arachnoid cyst resection- if there is no clinical
      presentation specific to the arachnoid cyst itself.

PMID- 27891398
TI  - An Unusual Evolution of Krukenberg Tumour: A Case Report.
AB  - Krukenberg tumours are rare metastatic tumours of the ovaries characterized by
      the presence of mucin-producing neoplastic Signet Ring Cell Carcinoma (SRCC). At
      first glance, this tumour may be confused with a primary ovarian tumour. Surgery
      and chemotherapy combination have led to improvement in prognosis, but it still
      remains severe. We report the case of a 60-year-old woman with a Krukenberg
      tumour rising from a low differentiated gastric adenocarcinoma. The patient was
      clinically stable for 26 months after surgery until she experienced a prompt
      decline and died of cerebral haemorrhage within two weeks. The aim of this
      article was to give an overview of the Krukenberg tumour starting from our case
      report and comparing it with clinicopathological characteristics of this
      pathology derived from a review of recent literature.

PMID- 27891399
TI  - Effect of Citalopram in Combination with Omega-3 on Depression in Post-menopausal
      Women: A Triple Blind Randomized Controlled Trial.
AB  - INTRODUCTION: Depressive disorder is a common and disabling disorder that causes
      high rates of morbidity and mortality. Citalopram is an antidepressant drug, of
      the Selective Serotonin Reuptake Inhibitor (SSRI) class that has been used for
      geriatric depression since a long time ago. Prescription of omega-3 in geriatric
      depression has been increased recently; because of more favorable profile of
      their side effects. Some of the studies reported that omega-3 is effective in
      prevention or treatment of depressive disorders than Citalopram. However, there
      are contradictory studies too. AIM: This study aimed to investigate the effect of
      a combination of omega-3 and citalopram in the treatment of women with post
      menopausal depression. MATERIALS AND METHODS: This triple-blind randomized
      controlled trial was conducted on 60 women with post-menopausal depression who
      were referred to the Hamadan Fatemieh Hospital. After the participants completed
      the DSM-IV questionnaire and depression was confirmed by a psychiatrist,
      participants were assigned randomly into two-intervention and control groups. The
      patients in the control group received 20mg citalopram along with a placebo while
      patients in the intervention group received 20mg citalopram and 1g of omega-3. At
      baseline and at the end of the first, second, and fourth weeks, all of the
      participants answered the Beck's Depression Inventory (BDI). Descriptive
      statistics and t-test, repeated measures analysis of variance and Bonferroni post
      hoc test was used to analyse the data. RESULTS: The depression score was 6.1+/
      2.41 in intervention and 25.22+/-10.04 in control group, four weeks after
      intervention. A decreasing trend was observed in the mean depression scores of
      the intervention group during the study. Using repeated measures analysis of
      variance, a significant difference was observed between the mean depression
      scores of the two groups at the four measurement time-points (p<0.001). The mean
      depression scores of the intervention group were significantly lower than the
      control group either two weeks (p< 0.001) or four weeks after the treatments (p<
      0.001). CONCLUSION: Using omega-3, can reduce the severity of depression in post
      menopausal women.

PMID- 27891400
TI  - Prevalence of Human Papilloma Virus Infection in Young Primiparous Women During
      Postpartum Period: Study from a Tertiary Care Center in Northern India.
AB  - INTRODUCTION: Assessment of high-risk Human Papilloma Virus (HPV) prevalence is
      important for monitoring long-term decrease in cervical cancer after
      implementation of the prophylactic HPV vaccination. AIM: To determine the
      prevalence of high-risk HPV infection and cytological abnormalities in young
      primiparous women in the age group of 16-26years. MATERIALS AND METHODS: In this
      cross-sectional study, 214 primiparous women aged 16-26years were recruited from
      a public tertiary health care center postpartum clinic between June 2013 and May
      2014. Cytological analysis was performed by Pap smear test and patients underwent
      sampling with cervical brushes for HPV-DNA detection and typing by a PCR-based
      assay for HPV types 16, 18, 33 and 45. RESULTS: High-risk HPV was detected in 41
      (19.2%) women. HPV 16 was found to be most prevalent with 17 (7.9%) samples
      testing positive, followed by HPV 18 in nine (4.2%), HPV 45 in six (2.8%) and HPV
      31 in four (1.8%) women. Five women tested positive for more than one HPV types.
      There were no cases of intraepithelial lesions or cervical cancer. One patient
      who had Atypical Cells of Undetermined Significance (ASCUS) on cytology tested
      negative for all four HPV genotypes. CONCLUSION: This study provides a geographic
      baseline data of high-risk HPV prevalence in young Indian women before
      implementation of a vaccination program. The results are important for comparison
      with other global regions and monitoring the effect of HPV vaccination.

PMID- 27891401
TI  - Premature Ovarian Failure: An Association with Autoimmune Diseases.
AB  - INTRODUCTION: Premature Ovarian Failure (POF) is the cessation of ovarian
      function before the age of 40 years. POF is reported to be associated with
      autoimmune diseases in 20-30% of cases. AIM: Patients presenting with idiopathic
      POF were screened for the presence of autoimmune disorders. MATERIALS AND
      METHODS: Twenty patients with idiopathic POF were included in the study. Baseline
      investigation in all subjects included fasting serum FSH, LH, E2, progesterone,
      free T3, free T4, Thyroid-Stimulating Hormone (TSH) and Anti-Thyroperoxidase
      (anti-TPO) antibodies, testosterone and Dehydroepiandrosterone (DHEAS) levels.
      Fasting and post-glucose (2 hours after 75g of oral glucose) serum calcium and
      phosphate were estimated using appropriate assays in biochemistry laboratory.
      RESULTS: Seven patients (35%), who presented with secondary amenorrhea, had
      thyroid disorders and were already on thyroxine replacement therapy. One patient
      also had vitiligo. There was no history of adrenal disorder. Anti-TPO levels were
      elevated in two (10%) patients of secondary amenorrhea group. The levels of serum
      testosterone were low in three patients. Serum DHEAS levels were low in 13
      patients. Blood sugar levels (fasting and 2 hour post 75g glucose load) and
      fasting insulin levels were normal. Serum calcium and phosphate levels were
      normal in all the patients. CONCLUSION: Thyroid autoimmunity is the most common
      autoimmune disease associated with POF. The finding of low DHEAS in a large
      percentage of patients (65%), suggests possibility of adrenal dysfunction. This
      requires further testing for adrenal reserve and adrenal autoantibodies.

PMID- 27891402
TI  - Clinical Analysis of Ectopic Pregnancies in a Tertiary Care Centre in Southern
      India: A Six-Year Retrospective Study.
AB  - INTRODUCTION: Ectopic Pregnancy (EP) is a life-threatening emergency commonly
      encountered by medical practitioners where diagnosis can often be missed. Any
      woman in the reproductive age group, presenting with lower abdominal pain or
      vaginal bleeding must raise the suspicion of an ectopic pregnancy to prevent
      mortality and morbidity. AIM: To review all cases of EP and determine the
      incidence of EP. To study the high risk factors and know the types of clinical
      presentation, methods of diagnosis, outcome and complications. MATERIALS AND
      METHODS: This was a retrospective cohort study, conducted at a tertiary care
      medical teaching hospital in Pondicherry, India. Medical records of all women
      with an EP between 2009 and 2015 were retrieved. Demographic data, parity, risk
      factors, clinical features, mode of management and need for blood transfusion was
      noted. Main outcome measures studied were the incidence of EP, risk factors,
      mortality and morbidity in these women. STATISTICAL ANALYSIS: Data was entered in
      Microsoft Excel spreadsheet and analysed using SPSS software version 19.0. For
      categorical variables, data was compiled as frequency and percent. For continuous
      variables, data was calculated as mean +/- SD. RESULTS: Seventy-two EP were
      diagnosed during the six-year period with an incidence of 9.1/1000 pregnancies.
      Majority of women were aged 21-30years (51.39%), 27.8% women were nulliparous.
      The most common risk factors were previous abortion (36.1%) and pelvic surgery
      (37.50%). Fifteen cases (20.8%) were diagnosed in women who had tubectomy. The
      classic triad of lower abdominal pain, amenorrhoea and vaginal bleeding was seen
      in 29(40.3%) cases. Ultrasonography was required to arrive at a diagnosis in
      28(38.9%) cases. Urine pregnancy test was positive in 100% of cases. Majority
      (94.4%) were tubal ectopic pregnancies. Medical management with methotrexate
      alone benefitted 10(13.89%) of patients while another four required surgery for
      failed medical management. More than half of the patients (59.7%) required blood
      transfusion and two (2.8%) had transfusion related acute lung injury. No deaths
      were noted. CONCLUSION: Common risk factors for EP must be identified. Use of
      transvaginal ultrasonography and human chorionic gonadotropin assay have
      revolutionised the management of EP and serve as valuable adjuncts to early
      diagnosis and management.

PMID- 27891403
TI  - Efficacy of Transcutaneous Electrical Nerve Stimulation in the Treatment of
      Overactive Bladder.
AB  - INTRODUCTION: Overactive Bladder (OAB) accounts for 40-70% cases of incontinence.
      The etiology is unknown though detrusor instability is found in urodynamic
      evaluation of almost all cases. Detrusor instability or hyperreflexia can be
      inhibited by direct inhibition of impulses in the pre-ganglionic afferent neuron
      or by inhibition of bladder pre-ganglionic neurons of the efferent limb of
      micturition reflex. Transcutaneous Electrical Nerve Stimulation (TENS) is based
      on the gate control theory of abolishing the local micturition reflex arc. AIM:
      To assess the effectiveness and safety of TENS in idiopathic OAB. MATERIALS AND
      METHODS: It is a prospective experimental study to evaluate the effectiveness of
      TENS v/s placebo in reducing OAB symptoms. (n1=20, n2 =20). Ten treatment
      sessions (5 sessions/week) of 30 minutes, were conducted. RESULTS: There was a
      significant improvement in Overactive Bladder Symptom Scores (OABSS) in TENS
      group and 2 patients were completely dry following TENS therapy. CONCLUSION: In
      elderly women, patients with OAB where other co-medications have their own
      anticholinergic side effects and impairment of cognition is a concern, TENS can
      be a useful intervention. TENS units are safe, economical and easily commercially
      available.

PMID- 27891404
TI  - Is There Any Impact of Copper Intrauterine Device on Female Sexual Functioning?
AB  - INTRODUCTION: Intrauterine Device (IUD) is the most preferred modern
      contraceptive method in Turkey. Female Sexual Dysfunction (FSD) is defined as
      lack of one or more of the components in the sexual response cycle which includes
      sexual desire, impaired arousal and inability achieving an orgasm or pain with
      intercourse. FSD has multi-factorial aetiology. Advanced age and menopause,
      fatigue and stress, psychiatric and neurologic disease, childbirth, pelvic floor
      or bladder dysfunction, endometriosis, uterine fibroids, hypertension obesity,
      medication and substances, hormonal contraceptives, relationship factors are
      known risk factors for FSD. AIM: To investigate if IUD has any impact on female
      sexual functioning. MATERIALS AND METHODS: In this cross-sectional study subjects
      were divided into two groups. Study group consisted of 92 IUD-users (mean 5.1+/
      1.2 years) and the control group consisted of 83 women with no contraception.
      Female Sexual Function Index (FSFI) questionnaire was performed to both two
      groups. Women with a total score lower than 26.5 were considered as having sexual
      dysfunction. RESULTS: The prevalence of FSD was 57.1% among participants. IUD
      users had a lower total FSFI score comparing to control group but the difference
      was not statistically different (p=0.983). A positive correlation was found
      between total FSFI score and duration of IUD (p=0.003). CONCLUSION: No difference
      was found in terms of sexual dysfunction between IUD users and women with no
      contraception. The prevalence of FSD was very high in both groups which may be
      attributed to the socio-cultural factors such as embarrassment of women due to
      conservatism.

PMID- 27891405
TI  - Complete Heart Block in Pregnancy: A Report of Emergency Caesarean Section in a
      Parturient without Pacemaker.
AB  - Management of women with Complete Heart Block (CHB) presenting without pacing,
      during pregnancy and labour is debatable. Temporary pacemakers have been
      routinely inserted for labour and birth probably to withstand any haemodynamic
      variations. However, due to lack of large scale prospective studies, the
      necessity of this procedure has not been objectively assessed. Also, the most
      appropriate anaesthetic technique for caesarean section in women with CHB is yet
      to be clarified. We report herein the case of a pregnant woman with CHB who had
      uneventful emergency caesarean delivery under spinal anaesthesia without
      temporary pacing. She was an unbooked case detected with congenital CHB first
      time during active labour; echocardiography showed no structural cardiac disease
      and her heart rate increased with atropine. We suggest further research so that
      guidelines could be established to prevent unnecessary morbidity and expense of
      temporary pacemaker insertion. Newly diagnosed cases of asymptomatic CHB in late
      pregnancy should be worked up for chronotropic responsiveness using atropine and
      responsive cases may be managed without pacemaker.

PMID- 27891406
TI  - Amniotic Fluid Embolism with Isolated Coagulopathy: A Report of Two Cases.
AB  - Amniotic Fluid Embolism (AFE) is a catastrophic complication of pregnancy with
      high mortality rate. The most common clinical presentation is an abrupt onset of
      cardiopulmonary collapse. Here, we present an uncommon variant involving isolated
      disseminated intravascular coagulation that developed without antecedent
      cardiopulmonary disturbances. Both patients developed symptoms soon after
      delivery. Blood test was sent at 14 minutes postpartum for the second patient due
      to suspected amniotic fluid embolism. Fetal components were observed in the
      uterine veins of the lower uterine segments in both cases. Amniotic fluid
      embolism with disseminated intravascular coagulopathy typically progresses faster
      than disseminated intravascular coagulopathy associated with other causes and
      symptoms. It usually develops within two hours of delivery. Prompt recognition
      and treatment of this entity is crucial to survival.

PMID- 27891407
TI  - Successful Pregnancy Outcome in a Patient with Solitary Kidney Affected by
      Angiomyolipoma: A Rare Case.
AB  - Renal angiomyolipoma is a rare benign tumour and its occurrence during pregnancy
      is even rare. It is usually diagnosed incidentally. It can increase in size
      during pregnancy and can present acutely as rupture with retroperitoneal
      haemorrhage, mechanism of which is still unclear. We present a case of successful
      pregnancy outcome in a patient with congenital solitary kidney affected by
      angiomyolipoma, diagnosed incidentally at 19 years of age. The patient had
      conceived twice. Her antenatal and post partum period was uneventful both the
      times.

PMID- 27891408
TI  - Successful Obstetric Outcome in Dextrocardia with Situs Inversus and Moderate
      Pulmonary Hypertension- Rare Case.
AB  - Situs inversus is a rare congenital anomaly, which is characterized by right
      sided heart (Dextrocardia) and inversely rotated visceral organs of abdomen. In
      present case, the patient reported with G3p2l2, 34 weeks of gestational period
      along with breathlessness accompanied and labour pains. On further investigation,
      she was diagnosed as dextrocardia with situs inversus and moderate pulmonary
      artery hypertension along with severe iron deficiency anaemia. Patient had normal
      vaginal delivery with intra-partum and post-partum period. Normally, any patient
      having situs inversus has a normal life expectancy and is not associated with any
      significant morbidity or mortality.

PMID- 27891409
TI  - Distal Femur Locking Plate: The Answer to All Distal Femoral Fractures.
AB  - INTRODUCTION: Good results have been published by researchers with distal femur
      nail, dynamic condylar screw and even addition of a medial plate to a distal
      femur locking plate for treating distal femur fractures. By this study, we
      explore the capability of a distal femur locking plate to counter distal femur
      fractures of extra- articular, partial or intra- articular nature. Positive
      results have been published by various groups from all over the world. AIM: To
      study the functional and radiological outcome of distal femoral fractures in
      skeletally mature patients treated by open reduction and internal fixation with
      distal femur locking plate. MATERIALS AND METHODS: This was a prospective study
      conducted from January 2012 to March 2014 at the Government Medical College and
      Hospital (GMCH) with a 2 year follow-up. Twenty five skeletally mature patients
      with post-traumatic distal femur fractures were included. Patients with open
      grade 3B and 3C distal femur fractures, according to the Gustilo- Anderson
      classification and pathological distal femur fractures were excluded from the
      study. Patients with any fracture other than the distal femur in the ipsilateral
      limb were excluded from the study. Follow-up at 3 months, 6 months, 1 year and 2
      years was carried out and evaluation was done according to the Neer scoring
      system. The statistical data analysis was carried out using SPSS version 20 (IBM,
      Chicago, USA). The p-value <0.05 was considered significant. RESULTS: Following
      all principles of fracture reduction, union was achieved in all patients with
      mean time to radiological union being 19 weeks. The mean Range of Motion (ROM)
      was 109 degrees with 20 patients having a Neer score graded as excellent to
      satisfactory. Our study had nine cases which required additional surgeries. Out
      of these, all nine cases required bone grafting, three also required antibiotic
      cement bead insertion initially. Three patients developed complications in the
      form of infection (two cases) and mal-union (one case) during the course of our
      study, but were completely treated by the end of the study. CONCLUSION: Positive
      results can be obtained by distal femur locking plate alone as it is the main
      implant of choice for distal femur fractures of all varieties. Best outcome is
      expected if fracture fixation is done following all the basic principles of
      fracture fixation and taking benefit of the mechanical properties of a locking
      plate.

PMID- 27891410
TI  - Subperiosteal Schwannoma of Pelvis- A Rare Case and Review of Literature.
AB  - Schwannoma are benign tumours of the nerve sheath. They are commonly found in the
      soft tissue, but its presence in the bone is extremely rare. We herein present a
      case of 34-year-old man with two adjacent pelvic subperiosteal schwannomas.
      Computed Tomography (CT) scan showed osseous pressure erosion and Magnetic
      Resonance Imaging (MRI) showed two cystic signal intensity lesions, one near
      superior aspect of right posterior iliac wing and another inferior to it with
      adjacent cortical pressure erosion. The tumour was excised en bloc and on
      histopathological examination, the diagnosis was confirmed as subperiosteal
      schwannoma. To our knowledge, this is the first case report of subperiosteal
      schwannoma involving the pelvis. When a surface cystic lesion is encountered,
      subperiosteal schwannoma should be considered as a possible differential
      diagnosis.

PMID- 27891411
TI  - Unusual Presentation of Radial Nerve Entrapment with Lateral Humeral Condyle
      Fracture - A Case Report.
AB  - Lateral humeral condyle fracture is the second most common fracture around the
      elbow in pediatric age group. Acute neurological deficit as a consequence of
      nerve injury associated with lateral humeral condyle fractures is very uncommon.
      We report a rare presentation of a case of lateral humeral condyle fracture in a
      13-year-old boy with acute radial nerve palsy. Patient was operated through a
      modified anterolateral approach to the elbow with, exploration of the radial
      nerve and internal fixation of the fracture. Complete fracture union at 6 weeks
      with good range of movements and full neurological recovery at 12 weeks was seen.
      We report this case due to rare combination of radial nerve injury and lateral
      humeral condyle fracture. Importance should be given to a thorough neurological
      examination during initial clinical examination and proper pre-operative
      planning.

PMID- 27891412
TI  - Revisited: A Prospective Study on Functional Outcome of Internal Fixation of
      Tibial Pilon Fractures with Locking Plate using MIPO.

PMID- 27891413
TI  - Cost-Effective Recruitment need for 24x7 Paediatricians in the State General
      Hospitals in Relation to the Reduction of Infant Mortality.
AB  - INTRODUCTION: According to World Health Organisation (WHO), improvement of
      hospital based care can have an impact of upto 30% in reducing Infant Mortality
      Rate (IMR), whereas, strengthening universal outreach and family-community based
      care is known to have a greater impact. The study intends to assess how far gaps
      in the public health facilities contribute towards infant mortality, as 2/3rd of
      infant mortality is due to suboptimum care seeking and weak health system. AIM:
      To identify cost-effectiveness of employment of additional paediatric manpower to
      provide round the clock skilled service to reduce IMR in the present state health
      facilities at the district general hospitals. MATERIALS AND METHODS: A cross
      sectional observational study was conducted in a tertiary teaching hospital and
      district hospitals of 2 districts (Hooghly and Howrah in West Bengal). Factors
      affecting infant mortality and shift wise analysis of proportion of infant deaths
      were analysed in both tertiary and district level hospitals. Information was
      gathered in a predesigned proforma for one year period by verifying hospital
      records and by personal interview with service personnel in the health
      establishment. SPSS software version 17 (Chicago, IL) was used. The p-value was
      calculated by Fischer exact t-test. RESULTS: Available hospital beds per 1000
      population were 1.1. Percentage of paediatric beds available in comparison to
      total hospital bed was disproportionately lower (10%). Dearth of skilled medical
      care provider at odd hours in district hospitals resulted in significantly
      greater infant death (p < 0.0001), but was not seen in tertiary hospital. The
      investment for appointing four additional paediatricians for round the clock stay
      duty was found to be cost-effective. CONCLUSION: Provision of round the clock
      availability of skilled medical care may reduce hospital based infant mortality
      and it is cost-effective.

PMID- 27891414
TI  - Paediatric Urinary Tract Infection: A Hospital Based Experience.
AB  - INTRODUCTION: Paediatric Urinary Tract Infection (UTI) is one of the commonly
      encountered entities by paediatricians. Studies have shown easy vulnerability of
      paediatric urinary tract in any acute febrile illness and a miss in diagnosis
      could have long term consequences like renal scaring with its adverse effects.
      Bearing these evidence based preludes in view we designed our study to know the
      prevalence of UTI in Kashmir province. AIM: Aim of the present study was to know
      the prevalence of UTI in febrile children and to know the sensitivity of
      different imaging modalities like Renal and Urinary Bladder Ultrasonography
      (RUS), Voiding Cystourethrography (VCUG) and Dimercaptosuccinic Acid (DMSA) scan
      in diagnosing UTI. MATERIALS AND METHODS: A total of 304 patients, between 2
      months to 10 years, with axillary temperature of >= 100.4oF (38oC), who did not
      have a definite source for their fever and who were not on antibiotics were
      included in the study. Detailed history and through clinical examination was done
      to rule out any potential or definite focus of infection as per the predesigned
      proforma. Routine urine examination with culture and sensitivity, followed by RUS
      and VCUG was done in all patients where routine urine examination was suggestive
      of UTI. DMSA was done in only culture proven cases after 6 months to document the
      renal scarring. RESULTS: Out of 304 children, 140 were males and 164 were
      females, UTI was present in 40 patients who had fever without any apparent cause
      giving a prevalence of 13.2%. Escherichia coli (E. coli) were the commonest
      isolated organism, followed by Klebsiella and Citrobacter species. Renal and
      Urinary Bladder Ultrasonography (RUS) detected Vesicoureteral Reflux (VUR) in 25%
      (10/40) while VCUG showed VUR in 55% (22/40) giving a RUS sensitivity of 45% for
      detecting VUR. DMSA done only after 6 months in UTI diagnosed patients showed a
      renal scarring in 25% (10/40) patients. CONCLUSION: Missing a febrile paediatric
      UTI, can prove a future catastrophe if not timely diagnosed and treated.

PMID- 27891415
TI  - Urban Rural Comparison of Anthropometry and Menarcheal Status of Adolescent
      School Going Girls of Jodhpur, Rajasthan, India.
AB  - INTRODUCTION: Adolescence is the formative period of life. Poor adolescent health
      translates into poor maternal health leading to increased maternal morbidity with
      inter-generational consequences. AIM: To compare anthropometric, socio
      demographic, menstrual and nutritional status of rural and urban adolescent
      school going girls of Western Rajasthan, India. MATERIALS AND METHODS: A cross
      sectional comparative study was conducted in two rural schools and one urban
      school of Jodhpur region. Anthropometric, socio-economic (family history,
      menstrual history, maternal education) and dietary habit data of 327 (137 urban
      and 190 rural) school going adolescent girls aged 11-16 years were collected
      using structured questionnaires by a school based survey after consent from
      parents and school officials. Height and weight were taken using the standard
      procedure. Stunting (height for age) and thinness [Body Mass index (BMI) for age]
      were calculated as per the National Center for Health and Statistics (NCHS)
      standards. Statistical analysis was done using student t-test, fisher-exact test
      and Chi-square test. RESULTS: Mean height was significantly higher in urban girls
      while mean BMI of adolescents was significantly higher in rural areas as compared
      to their urban counterparts. Growth spurt was between 12-13 years showing maximum
      increase in mean height, coinciding with or immediately post-menarche. Menarche
      was one year earlier in urban girls as compared to rural girls (p<0.001).
      Thinness was more prevalent among females in urban areas and stunting was more
      common amongst girls residing in rural areas. CONCLUSION: Life style habits (poor
      dietary habits, sedentary life style) of the urban girls may contribute to an
      early menarche but rural girls despite having a later onset of menarche; have a
      lower final height which may be attributed to their poor nutritional status.
      Improving nutrition of rural girls and modifying the life style of urban girls
      and educating their mothers will reduce the disparity and lead to better health
      and development of adolescent girls in this region and this could be expected to
      improve maternal health in future.

PMID- 27891417
TI  - A Commonly Missed Well Known Entity- Acute Intermittent Porphyria: A Case Report.
AB  - Acute Intermittent Porphyria (AIP) usually presents with abdominal pain,
      peripheral neuropathy and psychiatric manifestations. Incidence of AIP being 5 in
      1,00,000. We present a case of an 11-year-old male child with multiple cranial
      nerve involvement, quadriparesis, focal convulsions, hypertension, hyponatremia
      with history of recurrent abdominal pain. His complete haemogram, ultrasonography
      (USG) abdomen, renal function tests were normal, he was also evaluated for
      tuberculosis which was negative. On further evaluation Electroencephalography
      (EEG) was suggestive of a generalised seizure disorder, MRI Brain suggestive of
      Posterior Reversible Encephalopathy Syndrome (PRES), Electromyography revealed a
      sensory motor axonal polyneuropathy and urine UV fluoresence test was positive
      for porphobilinogen which clinched the diagnosis of AIP.

PMID- 27891418
TI  - Cotoneaster and Neonatal Jaundice.

PMID- 27891416
TI  - Effect of Oral Iron on Markers of Oxidative Stress and Antioxidant Status in
      Children with Iron Deficiency Anaemia.
AB  - INTRODUCTION: Conflicting reports are available on the relationship of Iron
      Deficiency Anaemia (IDA) and iron therapy with oxidative stress. AIM: To study
      the levels of markers of oxidative stress and anti-oxidant status in children
      with IDA and to assess the effect of iron therapy on the same. MATERIALS AND
      METHODS: This prospective, single centre, hospital based study was a sub-study of
      a randomized controlled trial conducted in the Department of Paediatrics,
      Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar
      Pradesh in collaboration with the Department of Biochemistry (of the same
      institution) between October 2009 to February 2011. The sub-study was conducted
      in two parts: in the first part, levels of a biomarker of oxidative stress
      {Malondialdehyde (MDA)} and anti-oxidant enzymes {Superoxide Dismutase (SOD),
      Catalase (CAT), Glutathione Peroxidase (GPx)} were assessed and compared between
      67 children with IDA and 31 non-anaemic controls; in the second part, the effect
      of oral iron (6mg/kg/day) for eight weeks on these markers was studied in a
      subset of 35 children with IDA. The Bivariate correlations procedure was used to
      compute pair wise associations for a set of variables. T-tests (Independent
      samples t-test/Paired sample t-test) and Non-parametric tests (Mann-Whitney
      test/Wilcoxon signed-rank test) were applied as applicable for normally and non
      normally distributed data, respectively. RESULTS: Levels of anti-oxidant enzymes
      were significantly lower (p<0.001) in children with IDA as compared to controls,
      viz., SOD {median, 8.63 (IQR, 8.60-8.66) vs. 9.46 (IQR, 9.14-9.62) units/mg
      protein}, CAT {median, 8.49 (IQR, 8.46-8.50) vs. 9.10 (IQR, 9.04-9.14) MUmol
      H2O2/min/mg protein} and GPx {median, 49.19 (IQR, 48.99-49.60) vs. 56.94(IQR,
      56.80-57.14) mol NADPH oxidized /min/ mg protein}. Whereas, levels of MDA were
      significantly higher (p<0.001) in IDA group {median, 1.50 (IQR, 1.48-1.52) vs.
      1.24 (IQR, 1.20-1.27) moles/ml of serum}. Levels of Haemoglobin (Hb) and markers
      of iron status (serum iron, transferrin saturation and ferritin) had a very
      strong, highly significant positive correlation (p<0.001) with levels of anti
      oxidant enzymes (SOD, CAT, and GPx) but a very strong, highly significant
      negative correlation (p<0.001) with MDA. Total Iron Binding Capacity (TIBC) on
      the other hand, had a strong, highly significant (p<0.001) negative correlation
      with SOD, CAT, and GPx but a strong, highly significant positive correlation
      (p<0.001) with MDA. After eight weeks of daily iron therapy, a highly significant
      rise (p<0.001) from baseline was observed in levels of SOD, CAT, and GPx in
      subjects with IDA. On the other hand, MDA levels declined significantly
      (p<0.001). CONCLUSION: Lipid peroxidation is increased and anti-oxidant defenses
      lowered in IDA. These changes, however, may be mitigated effectively with oral
      iron therapy.

PMID- 27891419
TI  - Evaluation of Hospitalized Intractable Epileptic Children with SPECT Scan in
      Ahvaz, South West of Iran.
AB  - INTRODUCTION: Seizures are the most frequent neurologic disorder seen in
      childhood. Epilepsy is a group of disorders that includes an abnormally increased
      susceptibility to seizures. AIM: To examine the effectiveness of SPECT (Single
      Photon Emission Computerized Tomography) in detecting seizure foci in 21 Iranian
      children who had medically refractory epilepsy. MATERIALS AND METHODS: Children
      between 2 to 15 years of age with uncontrolled seizures were investigated using
      SPECT scan as a standardized protocol. RESULTS: In 16 cases (76.2%), likely
      seizure foci were evident, as were seen in the form of decreased regional blood
      flow, while in 5 cases (23.8%), SPECT scan results were normal. Left temporal
      lobe was the most common area which had decreased regional blood flow.
      CONCLUSION: SPECT scan can potentially be used to investigate children with
      uncontrolled seizures.

PMID- 27891420
TI  - Suboptimal Performance in Cleft Lip/Palate Children- Who is Responsible?
AB  - Information in this article is from an observational study comparing intelligence
      in children with cleft lip and palate with normal children. Both groups performed
      "draw a man test", the investigator noted the attitude and behaviour of children
      and their parents. The study shows low, but normal intelligence quotient in
      children with oral defects as compared to normal. The probable reason for sub
      normal performance appeared to be overprotective attitude of parents and poor
      self esteem of children with oral defects.

PMID- 27891421
TI  - Imaging Modality of Choice for Pre-Operative Cochlear Imaging: HRCT vs. MRI
      Temporal Bone.
AB  - INTRODUCTION: Congenital inner ear malformations occur as a result of the arrest
      or aberrance of inner ear development due to the heredity, gene mutation or other
      factors. Ever since the availability of cochlear implants, pre-operative
      evaluation by imaging of temporal bone has gained much attention. Precise
      selection of the candidate for cochlear implant dependent on preoperative
      radiological investigations. Only CT (Computed Tomography) and MRI (Magnetic
      Resonance Imaging) can provide a better picture of anatomy and pathology. AIM: To
      compare pre-operative imaging findings of both MRI and High Resolution Computed
      Tomography (HRCT) temporal bone and to find the best modality of choice in
      patients with bilateral profound Sensorineural Hearing Loss (SNHL). MATERIALS AND
      METHODS: This was a prospective, longitudinal, observational study conducted
      between June 2010 to November 2012. A total of 144 temporal bones were evaluated
      in 72 children with bilateral profound SNHL with congenital inner ear
      malformations. Each temporal bone was considered as a single case (144 cases).
      All the patients underwent HRCT and high field MRI study. MRI study included T2 W
      axial 3D FIESTA (Fast Imaging Employing Steady-state Acquisition) sequence.
      Anatomic abnormalities in each temporal bone were described and noted. For
      complete and better evaluation of Vestibulo-Cochlear Nerve (VCN) additional 3D
      oblique parasagittal view was taken perpendicular to the internal auditory canal
      with a small Field Of View (FOV). RESULTS: HRCT and MRI allowed accurate
      detection of inner ear malformations in children with bilateral SNHL. Majority of
      the patients presented with multiple structural abnormalities of inner ear. The
      common pathologies detected in the study were semicircular canal abnormality
      (89/144) followed by cochlear abnormalities (39/144). Most common cochlear
      abnormality was Mondini's deformity (14/144). MRI demonstrated absent of
      vestibulo-cochlear nerve in 15 cases. CONCLUSION: Few abnormalities of inner ear
      are better illustrated on CT, while others are better showed on MRI. Hence,
      neither HRCT nor MRI of the brain and temporal bones appears to be adequate
      imaging modality rather they are complementary to each other for pre-operative
      imaging of cochlear implantation.

PMID- 27891422
TI  - Panvascular Disease in Familial Hypercholesterolaemia Treated with Endovascular
      Simultaneous Bilateral Carotid Stenting.
AB  - Familial Hypercholesterolaemia (FH) is a monogenic autosomal dominant disorder
      affecting 1 in 500 individuals. We report a case of 32-year-old female with FH,
      previously not on any treatment, who presented with recurrent bilateral Middle
      Cerebral Artery (MCA) territory strokes and dyspnoea on exertion due to severe
      panvascualar disease involving descending aorta, innominate, subclavian, common
      carotid, internal carotid and coronary vessels. Her complete clinical work up was
      done and was started on lipid lowering drug treatment and low calorie diet. She
      underwent simultaneous bilateral carotid stenting followed by coronary artery
      bypass surgery at a later date. In the present scenario we want to emphasize the
      importance of early detection and treatment of individuals with FH, failing of
      which results in premature and accelerated atherosclerosis causing multisystemic
      vascular disease with significant morbidity and mortality. Screening of first
      degree relatives is important owing to the autosomal dominant inheritance pattern
      of the FH.

PMID- 27891423
TI  - Mercedes-Benz Sign.

PMID- 27891424
TI  - A Study on the Efficacy of the Addition of Low Dose Dexmedetomidine as an
      Adjuvant to Lignocaine in Intravenous Regional Anaesthesia (IVRA).
AB  - INTRODUCTION: Intravenous Regional Anaesthesia (IVRA) is a simple, effective
      method of providing anaesthesia for short duration surgical procedures on the
      extremities, its chief drawbacks are tourniquet pain, short duration of block and
      absence of post-operative analgesia. Dexmedetomidine is known to reduce
      anaesthetic requirements and also provide analgesia to the patient. AIM: To
      evaluate the efficacy of dexmedetomidine as an adjuvant to lignocaine in IVRA
      with respect to the quality of the block, tourniquet pain and post-operative
      analgesia. MATERIALS AND METHODS: A prospective, randomized, double-blinded study
      was conducted on 60 patients scheduled for orthopaedic surgery of the upper limb,
      of American Society of Anaesthesiologist's physical status grades I and II. They
      were divided into two groups of 30 each. The control group C received 40ml of
      0.5% lignocaine with saline and Group D received dexmedetomidine 0.5MUg/kg added
      to 40ml of 0.5% lignocaine. The time taken for the onset and recovery of sensory
      and motor block, incidence of tourniquet pain, intra-operative and post-operative
      Visual Analogue Scale (VAS) scores, duration of post-operative analgesia and any
      side effects were noted. Student t-test was used for evaluation of the
      demographic data, haemodynamic variables, the onset and recovery times of block,
      duration of analgesia and intra-operative analgesic consumption and tourniquet
      pain. Friedman's test was used for intra-operative and post-operative VAS and
      sedation scores. RESULTS: The onset time of both sensory and motor block were
      significantly shortened, the recovery of sensory and motor block was prolonged,
      the incidence of tourniquet pain was comparatively lesser and there was
      significantly increased duration of post-operative analgesia in the
      dexmedetomidine group. Haemodynamic parameters were similar in both groups.
      CONCLUSION: The addition of 0.5MUg/kg of dexmedetomidine as an adjuvant to IVRA
      effectively enhances the anaesthesia and post-operative analgesia obtained with
      lignocaine. The low dose of dexmedetomidine was effective and did not cause any
      major side effects.

PMID- 27891425
TI  - Estimation of Skin to Subarachnoid Space Depth: An Observational Study.
AB  - INTRODUCTION: In a patient, the skin to Subarachnoid Space Depth (SSD) varies
      considerably at different levels of the spinal cord. It also varies from patient
      to patient at the same vertebral level as per age, sex and Body Mass Index (BMI).
      Estimation of the skin to SSD reduces complications related to spinal
      anaesthesia. AIM: To measure the skin to SSD in the Indian population and to find
      a formula for predicting this depth. MATERIALS AND METHODS: Three hundred adult
      patients belonging to American Society of Anaesthesiologist class I and II,
      undergoing surgery using spinal anaesthesia in various surgical specialities of
      Gauhati Medical College were selected by systemic sampling for this prospective,
      observational study. Patients were divided into three groups: Group M containing
      male patients, Group F containing non-pregnant female patients, and Group PF
      containing pregnant female's patients. SSD was measured after performing lumbar
      puncture. The relationship between SSD and patient characteristics were studied,
      correlated and statistical analysis was used to find a formula for predicting the
      skin to SSD. Statistical analysis was done using Statistical Package for Social
      Sciences (SPSS 21.0, Chicago, IL, USA). One-way ANOVA with post-hoc(Bonferroni
      correction factor) analysis was applied to compare the three groups. Multivariate
      analysis was done for the covariates followed by a multivariate regression
      analysis to evaluate the covariates influencing SSD for each group separately.
      RESULTS: Mean SSD was 4.37+/-0.31cm in the overall population. SSD in adult males
      was 4.49+/-0.19cm which was significantly longer than that observed in female's
      4.18+/-0.39cm which was comparable with SSD in parturient 4.43+/-0.19 cm. The
      formula for predicting the skin to SSD in the male population was
      1.718+0.077*BMI+0.632*Height, in nonpregnant female population was
      1.828+0.077*BMI+0.018*Height+0.007*Age and 0.748+0.209*BMI+4.703*Height
      0.054*weight in parturient females, respectively. CONCLUSION: Skin to SSD
      correlated with the BMI in all the patients in our study.

PMID- 27891426
TI  - Palatonasal Fistula Repair - A Case of Unanticipated Difficult Intubation.
AB  - Patients with present or previous history of facio-maxillary trauma will mostly
      be associated with a difficult airway. Surgical correction of these injuries
      might not always correct the altered airway. We report a case of palatonasal
      fistula following an old facio-maxillary fracture, which has led to
      interpretation of a difficult airway into a normal one. The patient was found to
      be having difficult airway during direct laryngoscopy which caused failure to
      intubate initially. Though, the patient was successfully intubated in the third
      attempt by senior anaesthesiologist making use of manoeuvres and equipment
      available, it made an impact for us to do a proper pre-op evaluation of patients
      with history of surgical correction of facial injuries and also for being
      prepared for can't ventilate and can't intubate situation in such type of cases.
      Through, this case report we stress the importance of airway anatomical
      alterations following facio-maxillary trauma and their corresponding management.

PMID- 27891427
TI  - Anaesthetic Management of a Case of Down's Syndrome with Achalasia Cardia.
AB  - Achalasia cardia is a disorder of the gastrointestinal tract characterized by
      dilatation of the oesophagus and collection of food and fluids in the oesophagus
      leading to massive regurgitation and aspiration of gastric contents. Down's
      syndrome has multisystem effects which can also present as difficult airway.
      Here, we present a case of a 14-year-old girl, a case of Down's syndrome with
      Achalasia cardia and mitral valve prolapse posted for Heller's cardiomyotomy.
      Anaesthetic concerns were difficult airway due to Downs's syndrome, massive
      aspiration risks of Achalasia cardia and haemodynamic instability due to mitral
      regurgitation. In spite of proper preparation of the patient there was massive
      regurgitation of oesophageal contents during intubation which was managed
      successfully. Haemodynamic changes due to mitral valve prolapse also had to be
      taken care of during the intraoperative period. Postoperative period was
      uneventful and the child was discharged after one week.

PMID- 27891428
TI  - Fiberoptic Guided Retrograde Intubation in an Anticipated Difficult Airway:
      Revival of an Antiquated Technique.
AB  - Retrograde intubation is an invaluable technique which can be helpful in
      anticipated difficult airway situation. In this advanced era where fiberoptic
      intubation and video laryngoscopes are in abundant use, retrograde intubation is
      a forgotten technique. However, it may be useful in various difficult airway
      situations in this advanced era. In our case the patient had a bitter experience
      with previous fiberoptic intubation. Owing to that we had planned and performed a
      fiber optic guided retrograde intubation, where we had kept the fiberoptic
      bronchoscope in the pharynx keeping larynx and vocal cords in the focus to
      facilitate the emergence of guide wire through one of the nostrils as well as
      direct visual confirmation of intubation. This fiber optic guided retrograde
      intubation is a first reported case of its kind in a predicted difficult airway
      which can be beneficial in different difficult airway situations.

PMID- 27891429
TI  - Delayed Recovery from Anaesthesia: Missing Information.

PMID- 27891430
TI  - Study of Barrier to Help Seeking and its Relationships with Disability in
      Patients with Headache.
AB  - INTRODUCTION: Headache is among the first three most prevalent disorders with a
      wide treatment gap due to barriers in help seeking. Headache has been associated
      with disability. However, the relationship of barriers to help-seeking and
      disability are unexplored. AIM: To find out the barriers to help seeking and its
      relationship with headache related disability in patients with headache.
      MATERIALS AND METHODS: In this hospital based cross-sectional study, 200
      consecutive subjects with headache attending a tertiary care centre were
      recruited as per selection criteria and assessed with Sociodemographic & Clinical
      Proforma, Mini International Neuropsychiatric Interview (MINI), Barriers to Help
      Seeking Scale (BHSS), The Henry Ford Hospital Headache Disability Inventory
      (HDI). RESULTS: High mean score was observed on BHSS subscale need for control
      and self reliance (19.45; SD +/-9.66) and minimizing problem and resignation
      (10.02; SD +/-6.98). Mean score on the HDI was 25.65 (SD +/- 14.09).
      Socioeconomic status of the patient was statistically significant and positively
      associated with need for control and self reliance (p=0.035), concrete barriers
      and distrust of care givers (p=0.039), emotional control (p=0.005), and privacy
      (p=0.002). Occupational status had significant association with need for control
      and self-reliance (p=0.01), minimizing problem and resignation (p=0.033), and
      emotional control (p=0.006). Score on hospital headache disability inventory
      significantly predicted the value of score on concrete barriers and distrust of
      caregivers domain of HDI (p=0.001). CONCLUSION: Autonomy and under estimation of
      seriousness of headache are common barriers to help seeking. Pattern of help
      seeking barriers may vary with socio-economic status and occupational status,
      while disability varies with gender and severity of headache. Headache associated
      disability is positively associated with concrete barriers.

PMID- 27891431
TI  - Excessive Daytime Sleepiness in Schizophrenia: A Naturalistic Clinical Study.
AB  - INTRODUCTION: Excessive Daytime Sleepiness (EDS) and sleep problems are common in
      patients with schizophrenia. The symptom of EDS in schizophrenia can be
      attributed to various causes including neurobiological changes, sleep disorders,
      medication or as a symptom of schizophrenia itself. EDS as a symptom in
      schizophrenia has been understudied. AIM: To assess the prevalence of EDS and to
      the study the same in patients with first episode and chronic schizophrenia.
      MATERIALS AND METHODS: In this cross-sectional study 100 patients suffering from
      schizophrenia as per International Classification of Diseases (ICD-10) criteria
      were evaluated for sleep quality using the Pittsburgh Sleep Quality Index (PSQI)
      and EDS using the Epworth Sleepiness Scale (ESS). The severity of illness was
      assessed by Positive and Negative Symptom Scale for Schizophrenia (PANSS) while
      cognition was assessed using the Frontal Assessment Battery (FAB) and the Trail
      Making Test A and B. The data was statistically analysed. RESULTS: A total of 100
      patients (72 male and 28 female) aged 18 to 64years (mean age 30.63 years) were
      studied. Poor sleep quality (PSQI > 6) was exhibited by 83% of patients.
      Excessive daytime sleepiness (ESS > 7) was found in 32% of patients. There was no
      statistically significant difference in various parameters according to the age,
      duration of illness or gender. However, first episode patients differed in having
      better sleep quality than patients with chronic schizophrenia (p=0.0002).
      Cognition was not affected by sleep quality. CONCLUSION: A high prevalence of
      sleepiness and poor sleep quality was noted in the entire sample but it did not
      have any correlation with age and gender. It also did not affect the cognitive
      test scores. Further research in this area is warranted.

PMID- 27891432
TI  - Perceived HIV Related Stigma among Patients Attending ART Center of a Tertiary
      Care Center in Rural West Bengal, India.
AB  - INTRODUCTION: Despite the advent of modern technologies, India is still grappling
      with the HIV/AIDS pandemic. Stigma is one of the key aspects which can interfere
      with HIV test-seeking behaviour, care-seeking behaviour upon diagnosis, quality
      of care given to HIV-positive patients and perception and treatment of People
      Living with HIV/AIDS (PLHA) by communities, families, and partners. AIM: To
      determine the perceived stigma associated with HIV/AIDS and its correlates among
      PLHAs attending the Anti Retroviral Therapy (ART) centre of North Bengal Medical
      College, Darjeeling, West Bengal, India. MATERIALS AND METHODS: An observational
      cross-sectional study was conducted over a period of four months among 454
      patients aged >=18years attending ART centre of North Bengal Medical College.
      Perceived stigma among the study subjects were assessed using a face and content
      validated version of Berger's HIV stigma scale. Linear regression analysis was
      used for statistical analysis of the predictors of perceived stigma. Data were
      analysed using SPSS version 16 software. RESULTS: The majority of the study
      population had moderate to low stigma. Regression analysis showed that being on
      treatment with ART had the highest contribution towards stigma followed by gender
      and HIV serostatus of the patients. CONCLUSION: The patients attending ART centre
      of North Bengal Medical College had moderate to low level of stigma. In absence
      of any efficacious stigma reduction programs in this region, more work needs to
      be done to assist PLHA in coping with stigma.

PMID- 27891433
TI  - The Clinical Presentation and Outcome of the Institutionalized Wandering Mentally
      Ill in India.
AB  - INTRODUCTION: There are estimated 400,000 wandering mentally ill persons in
      India, found in poor physical state wandering on streets and railway stations;
      mainly treated either by government run Hospitals for Mental Health (HMH) or
      Psychiatry units of a Government Medical College (GMC). They require psychosocial
      rehabilitation along with treatment. AIM: To study the presentation, clinical
      profile and rehabilitative outcome of wandering mentally ill admitted in
      government psychiatric care facilities. The objective was to establish them as a
      distinct psychiatric inpatient population requiring special attention. MATERIALS
      AND METHODS: The study was a chart review of all wandering mentally ill patients
      institutionalized during a period of two years in two distinct government
      facilities. Additionally, clinical staff was interviewed for cross checking the
      data and for eliciting problems faced in management. The discharged patients were
      contacted to assess the present status. RESULTS: Forty seven patients in HMH and
      35 patients in GMC were studied. Wandering mentally ill patients were brought to
      mental health facility by helping person (30) and police (23). Majority of them
      (61) were picked up from streets and railway station. Most of them (56) belonged
      to <40 years age group and communication with them was difficult due to language
      barrier in 51. Diagnosed as Psychosis NOS (45) initially, they presented with
      poor physical condition, with positive viral markers (25) and pregnancy in
      females (4). Most common final diagnosis was schizophrenia (45) along with
      prominent negative symptoms and poor cognitive abilities. Forty three of them
      showed good improvement on treatment. Forty five gave their address; Relatives
      were found in 39 through police, post cards and social workers and were
      rehabilitated back to family. CONCLUSION: Wandering mentally ill constitutes a
      unique patient population with specific challenges different from other
      inpatients in management and rehabilitation. Provisions to take care of this most
      vulnerable group of the society and mechanisms to watch for their continuous
      implementation are required.

PMID- 27891434
TI  - Abdominal Epilepsy in an Adult: A Diagnosis Often Missed.
AB  - Abdominal Epilepsy (AE) is a variant of temporal lobe epilepsy and is commonly
      seen in pediatric age group. There are however, multiple reports of abdominal
      epilepsy in adolescents and even in adults. Chronic and recurrent
      gastrointestinal symptoms with one or more neuropsychiatric manifestations are
      often the presenting picture for a patient with AE. Such patients therefore, are
      more likely to consult a general practioner, a physician, a surgeon or a
      gastroenterologist than consulting a psychiatrist or a neurologist. We hereby
      present such a case of AE in an adult with review of similar reports.

PMID- 27891435
TI  - A Study of Clinical Profile and Quality of Life in Patients with Scabies at a
      Rural Tertiary Care Centre.
AB  - INTRODUCTION: Scabies is a contagious disease primarily related to poverty and
      overcrowding, it rapidly spreads from person to person specially in people with
      poor hygiene. We come across many patients from rural areas with scabies. In
      India the incidence ranges from 13% to 59% in rural and urban areas. Many people
      complain of sleep disturbances and affection of work and leisure activities due
      to itching. Very few studies are done in India about the affection of quality of
      life in such patients. AIM: To study the demographic details, clinical profile
      and quality of life in patients with scabies. MATERIALS AND METHODS: A
      prospective, observational and cross-sectional study conducted at Department of
      Dermatology and Venereology, rural based tertiary care centre, Gujarat for a
      period of 6 months from March to August 2015, after ethical approval from the
      institute. Study included all patients with clinical features suggestive of
      scabies. The data including age, sex, occupation, education, socioeconomic
      status, complaints, past history, family history and clinical features along with
      the questionnaire for affection of quality of life were recorded in predesigned
      proforma and detailed analysis was done. Total of 102 newly diagnosed scabies
      patients attending skin OPD were included in the study. RESULTS: Out of 102
      patients, 50.98% were males. The most common age group affected was 21-40 years,
      in 44.11% patients. Students were commonly affected with 41.17% followed by
      housewives with 20.58% cases. Most common lesion seen was papules in 84.3%
      followed by excoriations in 82.3% cases. Maximum 51.6% adults had small effect on
      quality of life while 62.5% children reported minimal effect on quality of life.
      CONCLUSION: Scabies is an important and commonly encountered health problem which
      is highly contagious and if not attended timely and adequately can affect the
      quality of life in the form of work affection, sleep disturbances and
      psychosocial problems in patients as well as its family members. This could be
      easily prevented if the patients of scabies are recognised and treated early and
      proper awareness is must to avoid recurrences. The profile of scabies patients
      helps in early recognition of scabies even at the peripheral centers.

PMID- 27891436
TI  - Platelet Rich Plasma: Efficacy in Treating Trophic Ulcers in Leprosy.
AB  - INTRODUCTION: Trophic ulcers secondary to leprosy pose a great stigma to the
      patients and remain a challenge to the treating dermatologists. The discovery of
      Platelet Rich Plasma (PRP) with its favourable role in wound healing is a boon
      for the patients. PRP introduces the growth factors directly into the wound and
      aids in rapid healing. AIM: To study the efficacy and safety of PRP in the
      healing of trophic ulcers secondary to Hansen's disease in a tertiary care centre
      in Southern India. MATERIALS AND METHODS: Based on inclusion and exclusion
      criteria, 50 patients were enrolled in the study. PRP was prepared by manual
      double spin method. After wound bed preparation, activated PRP was sprayed over
      the ulcer and occlusive dressings were applied. Same procedure was repeated every
      week until complete re-epithelisation or up to six sittings whichever occurred
      earlier. RESULTS: In our study, 46 patients (92%) showed complete healing. In 4
      patients (8%), there was marked reduction in wound size with partial re
      epithelization. In 88%, complete healing was seen after the fourth sitting. Mean
      time for ulcer healing was around 4.38 weeks. CONCLUSION: PRP therapy leads to
      faster rate of induction of granulation tissue with rapid healing. Healing had no
      direct statistical correlation with the size, site and duration of ulcer, the
      leprosy spectrum and associated motor deformities. It is a simple, safe and cost
      effective in-office procedure, albeit requiring an optimal set-up and expertise.

PMID- 27891437
TI  - Nevus Lipomatosus Cutaneous Superficialis - A Rare Hamartoma: Report of Two
      Cases.
AB  - Nevus Lipomatosus Cutaneous Superficialis (NLCS) is a rare benign hamartomatous
      disorder in which mature collection of adipocytes are present ectopically in the
      dermis. NLCS usually presents as multiple, soft, pedunculated, cerebriform,
      yellowish or skin colored papules, nodules, or plaques, mostly involving the
      pelvic or gluteal region. We herewith report two cases of adult onset classical
      NLCS. First case had a classical presentation with lesion on lower back while
      second case was associated with some unusual features like occurrence on pubic
      area and associated comedo-like lesions.

PMID- 27891438
TI  - Blastomycosis-Like Pyoderma- A Rare Case Report.
AB  - Blastomycosis-like pyoderma is a rare, cutaneous bacterial infection of skin,
      seen in malnourished individuals, in a poor state of health and manifests as
      vegetating skin lesions. It is an unusual tissue reaction possibly to bacterial
      infection, the most common organism being Staphylococcus aureus. This case report
      is of a 35-year-old male who presented with thick verrucous surfaced plaques and
      papules on trunk and extremities since 2 months. Investigations revealed anaemia
      with hypochromasia, neutrophilic leucocytosis, hypo-proteinemia and hypo
      albuminemia with reversal of A/G ratio. Pathergy test was negative. Pus on Gram's
      stain showed plenty of pus cells, and negative for AFB and fungal stain. On
      culture of pus grew Coagulase negative staphylococcus species. Biopsy showed
      acanthosis of epidermis with moderate lymphocytic infiltrates in dermis and
      focally a few neutrophils and histiocytes. Patient fulfilled the criteria for
      diagnosis of blastomycosis like pyoderma viz., presentation of large verrucous
      plaques with pustules and ulcers with elevated border, histologically
      neutrophilic infiltration and growth of one pathogenic bacterium on culture.
      Patient responded to long-term cefotaxime therapy.

PMID- 27891439
TI  - O'Brien's Granuloma- A Case Report.
AB  - Actinic granuloma is a self-limiting chronic disorder with elastolytic
      granulomas, mainly of the sun exposed skin and unknown pathogenesis. We report a
      case of a middle aged woman with multiple annular erythematous lesions.
      Histopathology revealed degenerated elastic fibres with histiocyte aggregates
      surrounded by multiple giant cells suggestive of elastolytic granulomas. She also
      had associated dyslipidemia and hypothyroidism. Actinic granuloma is relatively
      rare in the Indian population and needs to be differentiated from conditions like
      sarcoidosis and granuloma annulare.

PMID- 27891440
TI  - Radiation Therapy in Paediatric Orbital Granulocytic Sarcomas: Experience from a
      Tertiary Cancer Center.
AB  - INTRODUCTION: Orbital Granulocytic Sarcoma (OGS) is an uncommon manifestation
      associated with haematological malignancies. Chemotherapy remains the cornerstone
      of the treatment. The role of radiation is not well-defined. AIM: To evaluate the
      effect of radiation in OGS and to define an optimal dose for achieving adequate
      local control. MATERIALS AND METHODS: This was a retrospective analysis of 11
      patients who received radiation therapy to orbit for Granulocytic Sarcoma (GS)
      between 2007 and 2014 at a tertiary cancer center in India. Radiotherapy was
      planned by three dimensional conformal (3DCRT) techniques. Demographic and
      disease characteristics, including clinical, imaging, histopathology and
      treatment details in this patient cohort were recorded and their response to
      therapy was assessed. RESULTS: The median age was 7 years (Range: 2-16 years).
      There were 3 female and 8 male patients. Eight patients were diagnosed as Acute
      Myelogenous Leukemia (AML), two patients had Primary Orbital Granulocytic Sarcoma
      (POGS) and one had bi-phenotypic leukemia. Median dose was 24.5Gy (Range-15-45
      Gy). Two anterior oblique field design were used most commonly. Out of 11
      patients, 5 (45.4%) had complete response, 3 (27.27%) had partial response, 1
      patient had stable disease (9%) and 2 developed progressive disease (18%). Median
      follow-up was 24 months (Range 24-84 months). At last follow-up, 7 (63.6%)
      patients were alive and 4 patients (37.4%) were dead due to progressive disease.
      CONCLUSION: In patients with residual orbital disease after chemotherapy, low
      dose radiation can be used to improve local disease control and improve quality
      of life. Local conformal radiotherapy of 24-30 Gy in conventional fractionation
      appears optimal with excellent local control and minimal morbidity.

PMID- 27891441
TI  - Development and Testing of a Reliable and Valid Patient-Needs Questionnaire for
      Breast Cancer Inpatients in China.
AB  - INTRODUCTION: Breast cancer patients are demanding more active roles in their
      care, especially in the initial diagnosis and treatment stages. At present, there
      is no suitable patient questionnaire that appropriately incorporates Chinese
      language, habits, and cultural differences. AIM: To develop and validate a
      patient-needs questionnaire for female breast cancer inpatients in China.
      MATERIALS AND METHODS: The questionnaire structure was based on Maslow's model
      and a modern medical model. In the first step, a focus group was used to design
      125 questions, of which 64 constituted the initial questionnaire for item
      screening with a group of 115 hospitalized patients with breast cancer. Items
      were included or excluded based on the evaluation of eight statistical analysis.
      Ultimately, 38 items were selected and validated. The reliability and validity of
      the 38-item questionnaire were determined in a cohort of 323 patients. RESULTS:
      The scale was set up with the 38 selected items. The four primary areas were
      disease knowledge, medical environment, psychosocial parameters and sexual
      attitudes. Cronbach's coefficient was 0.959. The split-half reliability value was
      0.935. Principal component factor analysis extracted four common factors.
      CONCLUSION: Our new questionnaire, designed to assess the care needs of Chinese
      inpatients with breast cancer is reliable, sensitive, effective, independent and
      representative. It can be used in medical practice as a tool for a more complete
      assessment of patients' needs.

PMID- 27891442
TI  - A Retrospective Evaluation of Clinical Profile of Second Primary Head and Neck
      Cancer.
AB  - INTRODUCTION: Incidence of Second Primary Malignancy (SPM) after successful
      treatment of primary is increasing and may cause the problem for optimal
      treatment. AIM: This study was conducted retrospectively to analyse incidence,
      disease free survival between malignancies, pattern of treatment and outcome.
      MATERIALS AND METHODS: Sixteen out of 22 patients of previously treated cases of
      head and neck cancer those develop SPM of head and neck region managed over a
      period of January 2012 to December 2015 in Department of Radiotherapy-II, Pt. BD
      Sharma PGIMS, Rohtak were analyzed retrospectively. Sixteen patients with
      unresectable disease were given reirradiation with external beam radiotherapy.
      RESULTS: Median age of presentation of first malignancy was 27 years (Ranged 26 
      65 years), whereas median age was 60 years for second malignancy (range 45-71
      years). All patients were smokers during first malignancy; 87.5% (14/16) had
      historyof smoking during second malignancy. Oropharynx (50%) was most common site
      of presentation of primary tumor whereas oral cavity was most common site of
      presentation in second primary tumor. CONCLUSION: Incidence of Second primary
      head and neck tumor after successful treatment for primary Head and neck cancer
      are increasing due to newer treatment strategies, longer survival and follow up.
      Reirradiation, surgery and or chemotherapy are treatment modalities. However
      second primary tumor of this region are associated with poor prognosis.

PMID- 27891444
TI  - Paclitaxel Induced Acute ST Elevation Myocardial Infarction: A Rare Case Report.
AB  - Paclitaxel, is a frequently used anti-neoplastic agent and is included in various
      chemotherapy regimens. The life threatening cardio toxicity associated with its
      use and the still unclear pathophysiology, has limited the use of this drug.
      Acute myocardial infarction is a rare adverse event associated with this drug. We
      report a case of acute ST-elevation myocardial infarction induced by paclitaxel
      infusion in a patient of oesophageal carcinoma who was saved by percutaneous
      primary intervention. The authors emphasize the awareness of this side effect of
      Paclitaxel among the clinicians.

PMID- 27891443
TI  - A Randomized Prospective Study of Concurrent Chemo-Radiotherapy vs Accelerated
      Hyperfractionation in Advanced Cancer of Head and Neck.
AB  - INTRODUCTION: Locally advanced unresectable squamous cell carcinoma of head and
      neck has poor locoregional control when treated with conventionally fractionated
      Radiation Therapy (RT) alone. However, Concurrent Chemo-Radiotherapy (CRT) and
      altered fractionated RT schedules like Accelerated Hyperfractionation (AHF) are
      two different treatment strategies that have shown to be associated with better
      efficacy as compared to conventional RT alone in such cases. AIM: Aim of the
      study was to compare these two treatment strategies i.e., CRT and AHF radiation
      treatment to know which is better in terms of clinical outcome and toxicity in
      patients of locally advanced unresectable squamous cell carcinoma of head and
      neck. MATERIALS AND METHODS: A prospective randomized trial was done to compare
      the effect of CRT and of AHF radiation treatment in locally advanced unresectable
      head and neck cancer on 15 patients in each arm and followed up over three months
      period. RESULTS: At the end of three months after completion of treatment
      protocol, complete response was 62% in CRT arm and 53% in AHF arm. In CRT arm and
      AHF arm, Grade 3 skin reactions were observed in 100% and 87%, grade 3 mucosal
      reactions were in 62% and 67% of cases, respectively. Three patients died in CRT
      arm (two due to myelosuppression and associated infection; one during the
      treatment and another after two weeks of treatment completion. The third patient
      expired after one month of treatment completion at his native place due to
      unknown reason). One patient died in AHF arm (during treatment due to cardiac
      event). CONCLUSION: Efficacy of AHF was comparable to CRT with lesser toxicity.
      So the present study suggests that AHF should be preferred over CRT in locally
      advanced, unresectable, squamous cell head and neck cancer followed over three
      months non-treatment period.

PMID- 27891445
TI  - Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation.
AB  - Primary cancer arising from multiple organs is a well known fact. Synchronous
      tumours have been most commonly associated with kidney cancer. Bladder, prostate,
      colorectal and lung cancer are the most common synchronous primaries with Renal
      Cell Carcinoma (RCC) identified till date. We found metachronous tumours of
      breast with RCC in literature search which included both metastatic tumours as
      well second primaries. Overall, 25 cases of metastatic breast tumours and eight
      cases of second primary in previously treated RCC have been reported in the
      literature. Here, we are reporting a case of synchronous presentation of
      carcinoma breast with RCC which is very rare because most of the multiple
      malignancies reported in the literature are metastatic tumours or metachronous
      breast malignancy with RCC.

PMID- 27891446
TI  - Requirements for Minimum Sample Size for Sensitivity and Specificity Analysis.
AB  - Sensitivity and specificity analysis is commonly used for screening and
      diagnostic tests. The main issue researchers face is to determine the sufficient
      sample sizes that are related with screening and diagnostic studies. Although the
      formula for sample size calculation is available but concerning majority of the
      researchers are not mathematicians or statisticians, hence, sample size
      calculation might not be easy for them. This review paper provides sample size
      tables with regards to sensitivity and specificity analysis. These tables were
      derived from formulation of sensitivity and specificity test using Power Analysis
      and Sample Size (PASS) software based on desired type I error, power and effect
      size. The approaches on how to use the tables were also discussed.

PMID- 27891447
TI  - Oral Health Knowledge, Attitudes and Practice Behaviour among Secondary School
      Children in Chandigarh.
AB  - INTRODUCTION: Oral health knowledge is considered to be an essential prerequisite
      for health-related practices and better oral health. Healthy practices adopted at
      young age are more sustainable. AIM: Present cross-sectional exploratory study
      was planned to assess oral health knowledge and practices of secondary school
      students in Chandigarh, India. MATERIALS AND METHODS: A cross-sectional survey
      was under-taken amongst 1027 secondary level school students, in Chandigarh,
      India. After obtaining informed consent subjects were administered pretested self
      administered questionnaire addressing demographics, knowledge, attitude and
      practice behaviour of participants. Frequency analysis was done using descriptive
      statistics. RESULTS: Survey revealed that only 40% subjects brushed twice daily.
      About 17% reported use of dental floss and 20% used either mouthwash or tongue
      cleaner as adjuncts. A total of 58% had knowledge that infrequent brushing led to
      dental caries, staining of teeth, dental plaque and bleeding from gums. Most of
      them knew sweets (92.7%) and soft drinks (67.8%) affected dental health. Only
      12.9% visited dentist regularly after every 6-12 months. CONCLUSION: Efficacy of
      dental health education can be increased only if health programs are tailored to
      directly impinge on attitudes of targeted population, especially school children
      in whom healthy practices can be inculcated easily and be sustained for long
      times.

PMID- 27891449
TI  - Oral Health Status and Treatment Needs of Paniya Tribes in Kerala.
AB  - INTRODUCTION: The tribal communities of Kerala have been largely left out of the
      gains of the Kerala model of development. AIM: The study was aimed to obtain
      baseline data of oral health status and treatment needs of Paniyas, in Kerala,
      India. MATERIALS AND METHODS: A descriptive population based survey of adult
      Paniya belonging to index age groups of 35-44 years and 65-74 years was
      conducted. The study population comprised of 420 subjects drawn from three
      talukas by stratified cluster sampling. Modified version of WHO Oral Health
      Assessment Form (1997) was used to assess the oral health status. RESULTS: Caries
      prevalence was 40%. The mean DMFT in the 35-44 years age group was 1.52+/-1.95
      and in 65-74 age group it was 18.47 +/- 13.10. Oral mucosal lesions were seen in
      4.52% and 76.9% had periodontal disease. Tooth brushing was reported by 55.5% of
      the subjects. Paan chewing, with tobacco or without tobacco, habit was reported
      by 89.3%. Bi-variate analyses between the CPI scores and age groups showed high
      statistical significance. The maximum mean treatment requirement was for
      extraction (1.37 +/- 4.01) and was observed in 65-74 age groups. CONCLUSION: The
      lack of basic oral health care access is important for high oral disease burden
      in these populations. Efforts are to be done for basic oral health care facility
      to these marginal populations.

PMID- 27891448
TI  - Can Feulgen Stain be a Reliable Biomarker over PAP Stain for Estimation of
      Micronuclei Score?
AB  - INTRODUCTION: Malignant transformation of the Potentially Malignant Lesions (PML)
      in the oral cavity is associated with elevated mortality rate because of its
      aggressive and exceedingly invasive nature. Meticulous diagnosis and prompt
      therapy of PML may help prevent malignant conversion in oral lesions.
      Carcinogenic insult to oral cells results in chromosomal damage and formation of
      Micronuclei (Mn), before the development of clinical symptoms. AIM: To determine
      the genotoxic effect of smoking and chewing tobacco on target tissue using Mn
      assay and to evaluate the prevalence of other nuclear anomalies associated with
      it and to determine the reliability of feulgen stain for Mn assay over
      Papaincolau (PAP) stain. MATERIALS AND METHODS: PAP and feulgen staining was done
      to study Mn in individuals who were having tobacco habits (smoking and chewing)
      without lesion (n=30), individuals who were having tobacco habit (smoking and
      chewing) with PML (n=30) and apparently healthy subjects (n=30). Data was
      analysed for statistical significance using SPSS 17.0 by Kruskal - Wallis Test
      and Bonferronii test. RESULTS: Tobacco habits in the form of smoking and chewing
      have mutagenic effects on human chromosomes which is indicated by increased
      frequency of Mn in oral exfoliative cells. The mean Mn frequency using feulgen
      stain was found to be 12.27 with lesion, 10.23 with without lesion and 3.87 in
      controls. Whereas, metanucleated analysis revealed no significant correlation
      with the formation of Mn. Non-specific DNA stain (PAP) showed high numbers of Mn
      cells in all the groups compared to feulgen. Statistically significant difference
      (p<0.0001) was observed when both the stains were compared for Mn numbers.
      CONCLUSION: These findings indicate that the individuals having tobacco habits
      (smoking and chewing) with lesion have high number of Mn cells, thus supporting
      the assay to be used as a reliable biomarker to assess the genotoxic effect of
      tobacco in the oral mucosa. The reason for almost twice as high Mn in PAP stained
      smears is suggestive of cell injury which is collimated by formation of keratin
      bodies, resulting in its misinterpretation as Mn, leading to false positive
      results. Hence, it was concluded that PAP stain can be used to identify abnormal
      cytological changes resulting from mutagenic agent but not to interpret Mn.

PMID- 27891450
TI  - Age and Environment Determined Children's Preference Towards Dentist Attire - A
      Cross - Sectional Study.
AB  - INTRODUCTION: The attire of the dentist has an influence on child's behaviour in
      dental setup. Recent research has shown that the children have preferences
      towards the outfit worn by the dentist. AIM: The aim of the study was to
      determine the preference of children towards dentists' attire based on various
      age groups and environment. MATERIALS AND METHODS: A total of 534 children aged
      between 6-11 years participated in the study. Children were divided into three
      groups based on their age as younger, middle and older age groups. Photographs of
      the dentist in different attires such as white coat, surgical scrubs and regular
      outfit were shown to children and the questionnaire was evaluated by a single,
      qualified Paediatric dentist in two different environmental set ups, namely
      school and dental environment. The anxiety level was evaluated by using Modified
      Child Dental Anxiety Scale [MCDAS (f)]. Data was collected and tabulated.
      Statistical analysis was done using SPSS version 20.0. RESULTS: A statistically
      significant difference was evident in the preference level of children towards
      dentist attire (p-value= 0.002). There was a positive correlation in the
      preference level of children towards dentist attire in different age groups. A
      statistically significant difference was evident in the preference level of
      children towards the dentist attire in school and dental environment (p-value
      <0.001). CONCLUSION: Younger age group children preferred regular outfit and
      middle and older age group preferred white coat and surgical scrubs respectively.
      Children preferred white coat in school environment and surgical scrubs in dental
      environment.

PMID- 27891451
TI  - Assessing the Reliability of Digitalized Cephalometric Analysis in Comparison
      with Manual Cephalometric Analysis.
AB  - INTRODUCTION: For more than seven decades orthodontist used cephalometric
      analysis as one of the main diagnostic tools which can be performed manually or
      by software. The use of computers in treatment planning is expected to avoid
      errors and make it less time consuming with effective evaluation and high
      reproducibility. AIM: This study was done to evaluate and compare the accuracy
      and reliability of cephalometric measurements between computerized method of
      direct digital radiographs and conventional tracing. MATERIALS AND METHODS:
      Digital and conventional hand tracing cephalometric analysis of 50 patients were
      done. Thirty anatomical landmarks were defined on each radiograph by a single
      investi-gator, 5 skeletal analysis (Steiner, Wits, Tweeds, McNamara, Rakosi
      Jarabaks) and 28 variables were calculated. RESULTS: The variables showed
      consistency between the two methods except for 1-NA, Y-axis and interincisal
      angle measurements which were higher in manual tracing and higher facial axis
      angle in digital tracing. CONCLUSION: Most of the commonly used measurements were
      accurate except some measurements between the digital tracing with FACAD(r) and
      manual methods. The advantages of digital imaging such as enhancement,
      transmission, archiving and low radiation dosages makes it to be preferred over
      conventional method in daily use.

PMID- 27891452
TI  - Clinical Utility of Serum Homocysteine and Folate as Tumor Markers in Oral
      Squamous Cell Carcinoma - A Cross-Sectional Study.
AB  - INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) is a common malignancy
      involving head and neck. Identifying the markers of molecular levels or
      biochemical markers involving the various metabolic reactions associated with the
      initiation and biological behavior of individual tumors are very important in
      diagnosis and prognosis. AIM: To measure and compare the levels of serum
      Homocysteine (Hcy) and serum folate in OSCC patients, smoking group and healthy
      subjects and also to assess the clinical utility of serum Hcy as a potential
      tumor marker in OSCC. MATERIALS AND METHODS: The study group comprised of 60
      subjects, of whom 30 were classified as OSCC cases (GROUP I) and 15 were
      classified as smokers without OSCC (GROUP II). The control group included 15
      healthy individuals without smoking habit (Group III). Hcy was measured with High
      Performance Liquid Chromatography (HPLC). Folate estimation was done by
      Chemiluminiscence Immuno Assay (CLIA). Comparison of mean Hcy and folate values
      among the groups was done using ANOVA with Post-Hoc Games Howell test. Gender was
      compared using Chi-square test. Comparison of mean age was using ANOVA with Post
      Hoc Tukey's test. RESULTS: The mean serum folate level in OSCC patients was
      5.34ng/mL, 7.68ng/mL in smoking group and 10.99ng/mL in control group. There was
      a significant difference in the mean serum folate levels among the three study
      groups (p<0.001). The mean serum Hcy in OSCC patients was 23.58MUmol/L,
      17.46MUmol/L, in smoking group and 10.76MUmol/l in controls. There was a
      significant difference in the mean serum Hcy levels among the three study groups
      (p<0.001). CONCLUSION: The present study found an interesting association with
      serum Hcy and folate levels in OSCC which could be useful as a biochemical "Tumor
      Marker" and thereby providing insights into the onset and progression of the
      disease.

PMID- 27891453
TI  - Efficacy of Ketamine as an Adjunct to Local Anesthesia in the Surgical Removal of
      Impacted Mandibular Third Molars - A Split Mouth Prospective Controlled Clinical
      Study.
AB  - INTRODUCTION: The removal of impacted teeth is one of the most common procedures
      performed by oral and maxillofacial surgeons. Reduction of discomfort post
      operatively and efficient local anesthesia are imperative for success in surgical
      practice. At sub-anesthetic doses, ketamine has a noticeable analgesic action,
      which can be used to supplement local anesthesia with minimal side effects. AIM:
      To assess the efficacy of low-dose ketamine as an adjunct to local anesthesia in
      the management of pain, swelling and trismus after surgical removal of impacted
      mandibular third molars. MATERIALS AND METHODS: Twenty five patients with
      bilaterally symmetrical impacted mandibular third molars requiring surgical
      removal under local anesthesia were selected for the controlled clinical study.
      The third molar sites of all patients enrolled in the trial were randomly
      assigned into 2 groups: Local Anesthesia (Lignocaine) Alone [LAA] and Local
      Anesthesia plus ketamine [LAK]. 5ml of local anesthetic (Lignocaine Hydrochloride
      2% with epinephrine 1:100,000) was injected in the 'LAA' group while the 'LAK'
      group received 5ml of local anesthetic plus 0.2mg/kg ketamine. Patients were
      blinded to the solution used and the operator recorded the group (LAA or LAK) and
      the respective site (Right or Left) for analysis. Bilaterally symmetrical
      impacted mandibular molars were removed at an interval of 15 days. RESULTS:
      Facial swelling on post-operative days was significantly lower in the LAK group
      than in the LAA group (p<0.05). The pain scores on the VAS were significantly
      higher in the LAA group than in the LAK group (p<0.05). CONCLUSION: The role of
      ketamine in low doses as an analgesic and anti-inflammatory is evident in our
      study. The combination of a local anesthetic and sub-anesthetic doses of ketamine
      injected for surgical removal of impacted third molars provides good local
      anesthesia while alleviating post-operative sequelae for the patient by providing
      a degree of post-operative analgesia with less swelling.

PMID- 27891454
TI  - Efficacy and Safety of Intralesional Xantinol Nicotinate in the Treatment of
      Various Stages of Oral Submucous Fibrosis.
AB  - INTRODUCTION: Oral Submucous Fibrosis (OSMF) is one of the most prevalent
      potentially malignant disorders seen in South east population since ages. Despite
      the extensive amount of research held in this field, its treatment still remains
      a challenge. In this study, we present our experience in successfully managing
      OSMF with intralesional injections of a peripheral vasodilator namely xantinol
      nicotinate. AIM: To determine the efficacy and safety of intralesional xantinol
      nicotinate in the treatment of various stages of OSMF. MATERIALS AND METHODS:
      This parallel, prospective, clinical study included 60 patients clinically
      diagnosed with oral submucous fibrosis divided into two groups. Group I patients
      were subjected to intralesional xantinol nicotinate injections bi-weekly for a
      period of four months while Group II patients were given intralesional saline
      injections biweekly for four months. All the patients were instructed to perform
      home mouth opening physiotherapy exercises. At each visit, parameters like
      increase in interincisal distance, cheek flexibility, tongue protrusion and
      relief from burning sensation and any side effects were measured and recorded.
      The drop out figure was zero. RESULTS: At the end of four months, in Group I,
      there was an increase in mean values of interincisal distance, cheek flexibility
      and tongue protrusion (p<0.001). For burning sensation a significant decrease in
      mean value was observed (p<0.001). Whereas, in Group 2 the difference between pre
      treatment and post-treatment values was not statistically significant (p>0.001).
      On comparing the results of Group 1 and Group 2, statistically significant
      difference was observed (p<0.001). CONCLUSION: Xantinol nicotinate, a peripheral
      vasodilator, when injected intralesionally in OSMF patients not only provides
      relief from burning sensation but also results in increased mouth opening, tongue
      protrusion and cheek flexibility.

PMID- 27891455
TI  - Unmasking the Effect of Analgesics on Endodontic Diagnosis Using a Novel Bite
      Force Sensor Device: A Prospective, Randomized Clinical Trial.
AB  - INTRODUCTION: A definitive diagnosis is of primary importance before initiating
      any endodontic treatment; yet, there are occasions when the dental professional
      is unable to accurately reproduce the patient's chief complaint, as it can pose a
      dilemma and may require consideration of multiple variables in order to reach an
      accurate diagnosis. So to overcome this problem, a methodical approach in
      providing endodontic treatment should be implemented which includes diagnosis,
      definitive dental treatment and adjunctive drug therapy, known as the "3D"
      strategy. AIM: The purpose of this study was to evaluate the possible "masking"
      effect of these analgesics on endodontic diagnosis using a novel bite force
      sensor device. MATERIALS AND METHODS: A total of 90 patients with endodontic pain
      were selected and they were given either a placebo or 400 mg ibuprofen (brufen)
      or 50mg diclofenac sodium (voveron). Both patients and operators were completely
      blinded to the drugs administered. Bite force tolerance values were noted before
      and one hour after administration of medication using the self designed bite
      force sensor. RESULTS: The pre- and post-bite force tolerance values were
      tabulated for both contralateral and affected tooth. For the affected tooth,
      there was statistically significant difference between pre- and post-bite force
      tolerance values in Group I (i.e., ibuprofen) and Group II (i.e., diclofenac
      sodium) (p<0.05) with no significant difference observed in Group III (placebo).
      CONCLUSION: The easily available over the counter self administered analgesics in
      addition to providing symptomatic relief to patients suffering from symptomatic
      apical periodontitis may also cloud the definitive diagnosis of the clinician,
      thus jeopardising the treatment plan. The self designed bite force sensor was
      effective in arriving at a definitive diagnosis in teeth with chronic
      irreversible pulpitis with symptomatic apical periodontitis, where the allodynia
      has been camouflaged by the use of analgesics like ibuprofen and diclofenac
      sodium.

PMID- 27891456
TI  - Effect of Salivary pH on Color Stability of Different Flowable Composites - A
      Prospective In-vitro Study.
AB  - INTRODUCTION: Scientifically and clinically there has been lot of development in
      the field of aesthetic dentistry. However, there is limited or restricted
      information regarding the color stability of flowable composite materials. AIM:
      The aim of this study was to evaluate the spectrophotometric color stability of
      three different flowable composite materials with respect to three different pH
      of saliva. MATERIALS AND METHODS: The study included 90 different samples. Thirty
      samples in each composite group; (Group A: G-aenial universal flo; Group B: Z 350
      XT flowable; Group C: Esthet x flow). All samples from each group were immersed
      in distilled water for 24 hours. Total color difference (DeltaE) was recorded for
      each sample. After this 10 samples from each group were respectively immersed in
      6.5, 7 and 7.5 pH of artificial saliva. All samples were kept in dark room for
      seven days and then DeltaE for each sample was recorded and was compared to
      previous recorded DeltaE for the same sample. RESULTS: Maximum color change was
      seen irrespective of material in 6.5 pH of saliva. G-aenial universal flo showed
      least change irrespective of pH of saliva. CONCLUSION: Thus, the present study
      reveals that acidic pH level affects the coloration of composite resins by
      affecting the surface integrity and as reported in previous studies, various
      coloring agents in beverages and other dietary components assists the process due
      to absorption of these coloring substances into the resin matrix.

PMID- 27891457
TI  - Prevalence of Dental Caries Among Primary School Children of India - A Cross
      Sectional Study.
AB  - INTRODUCTION: In India, the trend indicates an increase in oral health problems
      especially dental caries, which has been consistently increasing both in
      prevalence and in severity. Children of all age groups are affected by dental
      caries. It becomes imperative to collect the data on prevalence of dental caries
      and treatment needs to provide preventive care. AIM: To assess the prevalence of
      dental caries and treatment needs of 6-11years old Indian school children.
      MATERIALS AND METHODS: This was a cross-sectional study. Sampling frame consisted
      of 6-11years old primary school children. Study sample consisted of 13,200
      children selected from 10 talukas of Belgavi District, Karnataka, India. Clinical
      examination for dmft and DMFT was carried out in the school premises by five
      teams, each consisting of one faculty, three postgraduate students and five
      interns from the KLE VK Institute of Dental Sciences, Belagavi, Karnataka, India.
      The examiners were trained and calibrated by the principal investigator.
      Statistical analysis was done using Chi-square and t-test. RESULTS: The overall
      caries prevalence was 78.9%, mean dmft was 2.97+/-2.62 and mean DMFT was 0.17+/
      0.53. The decayed teeth component was the principal component in both dmft and
      DMFT indices. The mean dmft in boys was higher compared to girls and it was found
      to be statistically significant (p<0.05). CONCLUSION: This study provided us with
      the baseline data, using which treatment was provided to all the children
      screened. The children were provided treatment at the camp site/dental
      hospital/satellite centers and primary health care centers according to the
      facilities available.

PMID- 27891458
TI  - An In-vitro Comparison of Nano Hydroxyapatite, Novamin and Proargin Desensitizing
      Toothpastes - A SEM Study.
AB  - INTRODUCTION: Dentinal Hypersensitivity (DH) is commonly encountered clinical
      condition in dental practice which affects 8-57% of the adult population
      presenting for dental treatment, but the treatment of the same remains doubtful.
      AIM: The purpose of this study was to evaluate and compare the effects of three
      different desensitizing agents (15% nano hydroxyapatite crystals; 5% novamin and
      8% proargin) on dentinal permeability and tubule occlusion in-vitro. Scanning
      Electron Microscope (SEM) was used to evaluate the effect of these commercially
      available desensitizing toothpastes. MATERIALS AND METHODS: A total of 40 disc
      shaped dentin specimens were dissected from extracted premolars. Dentin discs of
      1mm were obtained with the help of diamond discs. Ten specimens were randomly
      selected and allocated to the evaluation groups A (control group), B (Nano
      hydroxyapatite), C (Novamin) and D (Proargin). Each treatment group dentine disc
      specimen was treated with the respective slurry for two minutes for a period of
      seven days. Each disc was subjected to a pre- and post-treatment SEM analysis to
      evaluate the changes occurring in the dentinal tubules. RESULTS: The qualitative
      analysis showed no occlusion of the dentinal tubules in Group A (control group)
      and Group B (nano-hydroxyapatite) showed 98.1% tubule occlusion. Group C
      (Novamin) and D (Proargin) showed 83.1% and 69.1% tubule occlusion respectively.
      Quantitative analysis showed a statistical significant difference between Group B
      and D (p< 0.005) and no statistical significant difference between group B and C
      (p= 0.235). Similarly, there was no significant difference between Group C and D
      as (p=0.235). CONCLUSION: It was concluded that all the three desensiting agents
      were effective in the dentine tubule occlusion. In addition efficacy of nano
      hydroxyapatite toothpaste was greater compared to the other desensiting agents.

PMID- 27891459
TI  - Comparison of Antibacterial Efficacy of Turmeric Extract, Morinda Citrifolia and
      3% Sodium Hypochlorite on Enterococcus faecalis: An In-vitro Study.
AB  - INTRODUCTION: Sodium hypochlorite (NaOCl), the most commonly used irrigant, has
      many potential properties like its unique ability to dissolve pulp tissue,
      excellent antimicrobial activity, but has a cytotoxic effect when injected into
      periapical tissues. It is also known to produce allergic reactions, foul smell
      and taste, and potential for corrosion. Facultative organisms such as
      Enterococcus faecalis and aerobes like Staphylococcus aureus are considered to be
      the most resistant species and one of the possible causes of root canal treatment
      failure. So there is a need to find an alternative to sodium hypochlorite to act
      against these resistant microorganisms. AIM: To evaluate and compare the
      antibacterial efficacy of morinda citrifolia and turmeric extract with 3% NaOCl
      as a root canal irrigant, against E. faecalis and S.aureus. MATERIALS AND
      METHODS: The antimicrobial efficacy was assessed in vitro using agar well
      diffusion method. Agar plates were prepared using Brain-Heart Infusion (BHI)
      agar. Cultures of E.faecalis and S.aureus were grown in nutrient broth at 37
      degrees C. Plates were incubated for 24 hours at 37 degrees C and microbial zones
      of inhibition were recorded. Statistical analysis was performed using ANOVA.
      RESULTS: NaOCl (3%) showed larger zones of inhibition than herbal irrigants
      against both the microorganisms. Among the herbal irrigants, morinda citrifolia
      showed larger zones of inhibition than turmeric hydro-alcoholic extract and
      turmeric water extract which was statistically significant (p<0.05). CONCLUSION:
      NaOCl (3%) showed maximum antibacterial activity against E. faecalis, followed by
      morinda citrifolia and turmeric extracts. Considering the potential for
      undesirable properties of NaOCl, use of herbal alternatives in endodontics might
      prove to be advantageous.

PMID- 27891460
TI  - Assessment and Correlation of Urea and Creatinine Levels in Saliva and Serum of
      Patients with Chronic Kidney Disease, Diabetes and Hypertension- A Research
      Study.
AB  - INTRODUCTION: Serum urea and creatinine are most widely accepted parameters to
      assess Chronic Kidney Disease (CKD)status as well as to assess renal status in
      susceptible diabetic and hypertensive subjects. AIM: To assess and correlate the
      serum and salivary urea and creatinine levels of CKD, diabetes mellitus and
      hypertensive subjects. MATERIALS AND METHODS: This cross-sectional study was done
      on 120 subjects involving 30 CKD, 30 diabetic, 30 hypertensive subjects and 30
      healthy controls. After collection of saliva and blood samples, urea was analyzed
      by enzymatic calorimetric method and creatinine by Jaffe's method. Kruskal Wallis
      test and Mann Whitney U test were used for comparison between different groups
      and correlations between serum and salivary parameters were evaluated by applying
      Spearman's correlation test. The p-value <0.05 was considered statistically
      significant. RESULTS: The median serum and salivary urea and creatinine levels
      were highest in CKD group followed by diabetic, hypertensive groups and controls.
      The correlation coefficient for serum urea and salivary urea was 0.977 and for
      serum creatinine and salivary creatinine was 0.976, with p-value <0.001.
      CONCLUSION: This study showed that there is a significant positive relationship
      between salivary and serum urea and creatinine. Thus, salivary urea and
      creatinine levels can be used non-invasively to detect serum urea and creatinine
      levels respectively in renal disease and diabetic and hypertensive nephropathic
      cases.

PMID- 27891461
TI  - Comparison of Therapeutic Efficacy of Placental Extract with Dexamethasone and
      Hyaluronic Acid with Dexamethasone for Oral Submucous Fibrosis - A Retrospective
      Analysis.
AB  - INTRODUCTION: Oral Submucous Fibrosis (OSMF) is a potentially malignant disease
      of the oral cavity associated with betel nut chewing. The management of OSMF has
      been a subject of controversy and no definitive and widely accepted treatment is
      currently available for this condition. AIM: To retrospectively evaluate the
      therapeutic efficacy of two treatment regimens (placental extract with
      dexamethasone and hyaluronic acid with dexamethasone) for the treatment of OSMF.
      MATERIALS AND METHODS: The records of the patients diagnosed with OSMF were
      obtained from the departmental archives. A total of 25 records were selected and
      divided into two study groups based on the treatment regimens, as Group A
      (placental extract + dexamethasone) and Group B (hyaluronidase + dexamethasone).
      The records were studied for improvement in mouth opening and reduction in
      burning sensation. Descriptive statistics, paired t test and student's t test
      were used for statistical analysis. RESULTS: In Group A and Group B, the average
      increase in mouth opening from baseline record to 8th week of treatment was
      3.53+/-1.26mm and 3.65+/-1.42mm respectively and average decrease in burning
      sensation, noted by VAS scale, was 5.13+/-1.13 and 4.90 +/-1.29 respectively. The
      pre- and post-treatment differences were found to be statistically significant
      for both the groups (p<0.001) and for both the treatment outcomes. When the
      average difference of the treatment outcomes was compared between the two study
      groups, no statistically significant difference was noted (p>0.05). CONCLUSION:
      The results of the present study indicate that both the treatment regimens
      studied are equally effective in the treatment of oral submucous fibrosis.

PMID- 27891462
TI  - Evaluation of Efficacy of Three Different Materials Used in Cheiloscopy -A
      Comparative Study.
AB  - INTRODUCTION: The imprint produced by the lip is termed as 'lip print' and the
      name given to the examination of lip print is referred to as cheiloscopy. AIM:
      The present study was done to compare the efficacy of three different materials
      used in cheiloscopy - Sudan III, Indigo and Aluminium powder. MATERIAL AND
      METHODS: A total of 60 individuals belonging to the age group of 18-25 years were
      included in this study. Visible and latent lip prints were reproduced on white
      cotton fabric, white satin fabric and white clay cup. The results were
      statistically analysed using chi square test. RESULTS: Sudan III dye and
      Aluminium powder showed significant results when used for the development of
      visible lip prints (p<0.05), but didn't give any significant results for
      development of latent lip prints. Indigo dye gave significant results for
      development of both visible and latent lip prints (p<0.05). CONCLUSION: The study
      reveals the usefulness of visible and latent lip print in individual
      identification.

PMID- 27891463
TI  - Psychological Analysis of Oral Cancer Patients during Pre-operative Period in
      South Indian Population: A Prospective, Quantitative, Multicentre Study.
AB  - INTRODUCTION: Oral cancer is prevalent worldwide with high incidence of mortality
      and morbidity. It is associated with poor prognosis and low survival rate.
      Moreover, patients affected are more likely to develop psychological issues and
      thus, addressing psychological needs of such patients is crucial. AIM: The aim of
      our study was to assess the quality of life of oral cancer patients in the pre
      operative period, thereby providing them with the necessary psychological
      support. MATERIALS AND METHODS: A total of 206 patients, scheduled to undergo
      treatment for oral cancer were selected from various cancer centres in South
      India. After informed consent, 171 patients were finally analysed for their
      quality of life using Functional Assessment of Cancer Therapy-General (FACT-G)
      version 4; and Functional Assessment of Cancer Therapy Head and Neck (FACT-H&N),
      as a Quality of Life (QOL) survey. RESULT: Most of the patients had poor quality
      of life and were found to be emotionally distressed pre-operatively as they did
      not have proper emotional support from society. CONCLUSION: From the study it was
      observed that catering to the psychological needs of oral cancer patients is
      important and psychological counselling should be a part of a comprehensive
      treatment plan for such patients.

PMID- 27891464
TI  - Awareness of Eco-Friendly Dentistry among Dental Faculty and Students of King
      Khalid University, Saudi Arabia.
AB  - INTRODUCTION: Eco-friendly or green dentistry can be a reality by effectively
      designing dental clinics and using more eco-friendly materials in the clinical
      practice. AIM: To determine the awareness of eco-friendly dentistry among dental
      faculty and students in preparation for future implementation. MATERIALS AND
      METHODS: Assessment of knowledge regarding eco-friendly dentistry was done using
      an 18 item self-administered questionnaire among 160 participants. After baseline
      data collection, the intervention was done by educating participants with a power
      point presentation. The post-intervention data was then collected for analysis.
      Statistical analysis was done using Wilcoxon's signed rank test and one-way
      ANOVA. RESULTS: The educational intervention increased the knowledge about eco
      friendly dentistry confirming the importance of continuing education. There was a
      statistically significant gain in knowledge among the participants after the
      presentation. The gain was highest for department of Preventive Dental Sciences
      (PDS) followed by Substitute Dental Sciences (SDS), No specialty, Maxillofacial
      Dental Sciences (MDS), and Restorative Dental Sciences (RDS) respectively.
      (F=5.5091, p<0.05). CONCLUSION: Lack of knowledge of green dentistry amongst the
      dental fraternity is highly prevailing. The same can be substantiated with
      effective training in the respective fields if channelized through the curriculum
      in an educational set-up.

PMID- 27891465
TI  - Practice Perspectives of Left-Handed Clinical Dental Students in India.
AB  - INTRODUCTION: Handedness becomes important for students during their training
      period. Limited literature is available regarding the same. AIM: The purpose of
      this study was to assess the dental practice perspectives and determine the hand
      preference and discomfort level among the Left-Handed (LH) clinical dental
      students. MATERIALS AND METHODS: A 30-item survey tool was used to conduct a
      cross-sectional survey among four successive LH cohorts (third and final year
      undergraduates, dental interns and postgraduates) in all the dental colleges of
      Bengaluru, Karnataka, India, during the year 2014. RESULTS: A total of 84
      students completed the survey, response rate being 100%. About one-third (37%)
      reported that their institution was not properly equipped to accommodate LH
      students. Majority felt that LH dentists were at a higher risk of developing
      musculoskeletal complications. Mouth mirror handling showed equal distribution
      for handedness as compared to the other dental activities, whereas discomfort
      levels were negligible ("without any difficulty"). Dental practice perspective
      scores significantly correlated with the difficulty levels (r=-0.333, p<0.001).
      CONCLUSION: Overall, the left-handers had a right dental practice perspective and
      their responses indicate a need to address their issues empathetically.

PMID- 27891466
TI  - An In-vitro Evaluation of Retention, Colonization and Penetration of Commonly
      Used Denture Lining Materials By Candida albicans.
AB  - INTRODUCTION: Colonization of the surface by Candida albicans and related Candida
      species is one of the major concerns of denture lining materials. AIM: We
      evaluated retention, colonization and penetration of the four denture lining
      materials namely Molloplast B, Permaflex, GC Soft Liner and Ufi Gel Hard C by
      Candida albicans. MATERIAL AND METHODS: a) Evaluation of retention: Five test
      discs of each material with smooth surface on one side and rough on the other
      were prepared and surface roughness (Ra) was measured with profilometer.
      Retention of C. albicans to discs was monitored after one hour of incubation (37
      degrees C) with standardized (2.8 x 106 cfu/ml) washed cell suspension. Discs
      were stained with acridine orange and attached cells were counted using inverted
      microscope; b) Evaluation of colonization and penetration: Eight test discs of
      each material in sterile artificial saliva, were inoculated with C. albicans and
      incubated for six weeks. Two sections were cut across each test disc to provide
      three replicate samples. Candida cells on cut disc sections were fixed,
      dehydrated, air dried and viewed via fluorescence microscope; c) Evaluation of
      antifungal action: Two test discs of each material were placed onto diagnostic
      sensitivity testing the agar plate. After incubation at 37 degrees C for 24
      hours, the zone of inhibition formed around the samples were measured at four
      places, and the mean calculated. RESULTS: a) All rough surfaces showed higher
      retention of C. albicans than smooth surfaces. Among the smooth surfaces,
      Molloplast B and GC Soft Liner showed highest and lowest retention of C. albicans
      respectively (p=0.0090). Among the rough surfaces, the variation in the retention
      of C. albicans was not statistically significant; b) Penetration of C. albicans
      was observed through all three sections of the test discs of each material. There
      was no statistically significant difference among the test materials; c)
      Molloplast B and Permaflex produced a mean zone of inhibition of 16.9+/-4.8mm and
      14.80+/-3.8mm respectively. CONCLUSION: a) Smoother surfaces retain fewer cells
      than rough surfaces; b) Denture lining materials permit infiltration of Candida
      through their structure; c) Denture lining materials have insignificant anti
      fungal properties.

PMID- 27891468
TI  - Influence of Teaching Strategies and its Order of Exposure on Pre-Clinical Teeth
      Arrangement - A Pilot Study.
AB  - INTRODUCTION: Teeth arrangement is a vital skill for the undergraduate dental
      student. The attainment of skills depends largely on the methodology of teaching.
      In a dental curriculum, the students are exposed to a wide variety of inputs and
      teaching methodologies from different sources. The educational unit in dental
      school must identify the sequence of teaching methods that enhance the learning
      and practising ability of students. AIM: The aim of this study was to evaluate
      the effectiveness of three different teaching methodologies for teeth arrangement
      and compare the differences between the orders of exposure to each teaching
      methodology on the development of teeth arrangement skills. MATERIALS AND
      METHODS: The first year B.D.S students were study participants and were divided
      into three groups A, B, C. They were exposed to three teaching patterns namely
      live demonstration with video assisted teaching, group discussion with hand-outs
      and lectures with power point presentation. After each teaching methodology,
      their skill was assessed. The groups were exposed to three methodologies in
      different order for three arrangements. The scores obtained were analysed using
      Kruskal Wallis rank sum test and Dunn test for statistical significance. RESULTS:
      Significantly higher scores in the teeth arrangement procedure were obtained by
      the Group A students who were exposed initially to live demonstration with video
      assisted teaching. Difference in the scores was noted among and within the
      groups. The difference between Group A and Group C was statistically significant
      after both first and third teeth arrangement (p=0.0031, p=0.0057). CONCLUSION:
      The study suggests each pre-clinical practice should begin with a live
      demonstration to enhance immediate learning absorption followed by lectures with
      power point presentation and group discussion for retention of knowledge and
      memory retrieval.

PMID- 27891467
TI  - An In-vitro Comparative Study of Shear Bond Strength of Composite Resin to
      Bleached Enamel using three Herbal Antioxidants.
AB  - INTRODUCTION: If adhesive restorations are carried out imme-diately, the Shear
      Bond Strength (SBS) to bleached enamel is reduced. The use of antioxidants can be
      highlighted since it seems to be a more effective alternative to reduce or remove
      the residual oxygen and immediate improvement in SBS. AIM: The purpose of this in
      vitro study was an attempt to regain the lost bond strength, for which, the
      comparison of SBS of composite resin to bleached enamel was carried out using
      various antioxidants i.e., 5% grape seed extract, 5% pine bark extract, 5%
      pomegranate peel extract. MATERIALS AND METHODS: Labial enamel surfaces of 50
      extracted human maxillary central incisors were randomly divided into 5 groups
      based on the antioxidant used as follows: Group I (n=10): Bleaching with 40%
      hydrogen peroxide gel for 10 minutes, without the use of an antioxidant; Group II
      (n=10): Bleaching followed by the use of 5% grape seed extract solution; Group
      III (n=10): Bleaching followed by the use of 5% pine bark extract solution Group
      IV (n=10): bleaching followed by the use of 5% pomegranate extract solution; and
      Group V (n=10): Control group in which no Bleaching was done. SBS of the
      specimens was tested using universal testing machine. The data were tabulated and
      statistically analyzed using computer software Statistical Package for Social
      Sciences (SPSS) version 16.0. One-way analysis of variance (ANOVA) followed by
      Mann Tukey Post hoc test. RESULTS: Mean SBS values were compared in all the
      groups and there was a statistically significant difference present among the
      groups (p<0.05). The SBS values were observed to be significantly higher in
      unbleached teeth (control group) followed by 5% pine bark extract, 5% grape seed
      extract, 5% pomegranate extract and the group in which teeth bleached with no
      antioxidant used. CONCLUSION: The use of antioxidant immediately after bleaching
      the enamel surface, completely neutralizes the deleterious effects of bleaching
      and increases the SBS significantly. Among the antioxidants, 5% pine bark extract
      application after bleaching showed better bond strength.

PMID- 27891469
TI  - Comparison of Anchorage Pattern under Two Types of Orthodontic Mini- Implant
      Loading During Retraction in Type A Anchorage Cases.
AB  - INTRODUCTION: The orthodontic mini-screws are the mainstay of direct skeletal
      anchorage which requires minimal compliance and provides maximal anchorage
      control. However, the timing of initiation of orthodontic loading of these mini
      screws is not clearly established in the available studies. AIM: The purpose of
      this study was to determine the reciprocal effects on mini-screw implant with
      immediate loading in comparison to that of delayed loading during retraction.
      MATERIALS AND METHODS: The prospective clinical study included a sample of 25
      orthodontic patients in the age range of 18-25 years. All the cases were of bi
      maxillary proclination with Type-A anchorage demands. All the first premolars
      were indicated for extraction. A split mouth technique for each patient was
      utilized by loading mini-implant immediately after its placement on one side and
      the opposite side implant was loaded after a time lag of two weeks post
      insertion. Retraction force of 150g was applied for three months on each side.
      The displacement of the head and tail of the implant, molar anterior tooth
      retraction was measured on Orthopantomograph (OPG) taken at T1 (initial) and T2
      (after three months). A grid method with each 1mm magnified to 500 pixels was
      superimposed on OPG and the relative displacements were evaluated. Student's
      unpaired 't' test was used for comparison between left and right side and paired
      't' test for the parameters on the same side. The p-value equal to or less than
      0.05 was taken as statistically significant. RESULTS: The mean displacement of
      head of the implant on the immediate loading is 0.57mm where as the tail
      exhibited 0.75 mm. The head and tail of the implant on the delayed loading
      displaced by 0.35mm and 0.38mm respectively, on an average when data was
      analysed. Significant difference between the two types of loading was noted.
      CONCLUSION: Delayed loading is beneficial as compared to immediate loading during
      extraction space closure.

PMID- 27891470
TI  - Determinants of Smokeless Tobacco Consumption and its Cessation among its Current
      Users in India.
AB  - INTRODUCTION: Global Smokeless Tobacco (SLT) consumption is on the rise and
      constitutes a major Public Health problem. Controlling SLT intake is central to
      containing the increasing tobacco menace. AIM: The present study was undertaken
      to comprehensively explore various factors involved in SLT consumption and its
      cessation among current SLT users. MATERIALS AND METHODS: Present study was
      conducted among current SLT users visiting Department of Oral Medicine and
      Radiology, Manipal College of Dental Sciences (MCODS), Manipal University,
      Mangalore, Karnataka, India. A structured, pretested and self-administered
      questionnaire was employed for the present study. Knowledge, attitude, behaviour,
      worksite practices of respondents towards SLT consumption and its cessation,
      barriers to SLT cessation were explored. Information about socio-demographic
      variables was also collected. RESULTS: Overall, 170 current SLT users
      participated in the present study. Results revealed that the mean knowledge,
      attitude, worksite related practices and barrier scores were 9.96(55.33%),
      48.89(81.48%), 2.70(33.75%) and 54.25(60.27%) respectively. Correlation analysis
      revealed significant association of socio-demographic factors with knowledge,
      attitude and worksite related practices (p<0.05). SLT cessation related practices
      revealed that majority wished to quit (90%) and significant associations were
      noted amongst wish to quit with higher attitude scores; actual quit attempts with
      higher attitude, lower barrier scores and difficulty to quit with higher barrier
      scores (p<0.05). CONCLUSION: The present study draws attention towards
      involvement of complex interactions of various parameters including socio
      demographic factors in SLT consumption and its cessation. Hence, it is imperative
      to implement multifactorial SLT control approach in order to contain tobacco
      menace spread across the globe.

PMID- 27891471
TI  - Comparison of Gingival Health and Salivary Parameters among Autistic and Non
      Autistic School Children in Riyadh.
AB  - INTRODUCTION: Autism is a neuro-developmental disorder which is manifested as
      impairment of social interaction, communication and a repetitive behaviour.
      Autism can obscure dental treatment for the affected patients; furthermore,
      children with autism commonly have destructive oral habits. AIM: The aims of this
      study were to evaluate the Modified Gingival Index (MGI), Plaque Index (PI),
      salivary pH and buffering capacity of the saliva among autistic children compared
      to normal children in Riyadh City that may provide baseline data to enable
      comparison and future planning of dental services for autistic children.
      MATERIALS AND METHODS: A total of 50 children diagnosed with autism (mean age 8.5
      years) were selected from Azzam Autism School, Riyadh City. The control group
      consisted of 50 non-autistic school children (mean age 8.7 years), gender
      matched, selected from Outpatient Clinic, Riyadh Colleges of Dentistry and
      Pharmacy. MGI, PI, salivary pH and salivary buffer capacity tests were done for
      all participants. The buffering capacity of the stimulated saliva was grouped
      under 'very low', 'low' and 'normal'. Pearson's Chi square and one way ANOVA were
      used to find statistical significance if any among the autistic and the normal
      control group. RESULTS: The results of the study showed that the mean +/-
      standard deviation of MGI, PI and pH of unstimulated resting saliva for autistic
      group were 1.82 +/- 0.65, 1.92 +/- 0.35 and 6.8 +/- 0.5 respectively. Normal
      control group had values 1.35 +/- 0.85, 1.44 +/- 0.43 and 7 +/- 0.4 respectively.
      A statistically significant difference between both groups for all parameters was
      found. Salivary buffering capacity was found to be normal for the majority among
      both groups. However, 60% children among the autistic group presented with normal
      buffering capacity of the stimulated saliva as compared to 70% among the normal
      control group. However, this difference was not statistically significant (p =
      0.544). CONCLUSION: Children with autism appear to have higher gingival
      inflammation, poor oral hygiene and a slightly lower salivary pH as compared to
      healthy control group. Special oral health programmes regarding treatment and
      maintenance of good oral health should be taken in consideration for autistic
      children.

PMID- 27891472
TI  - Oral Health Related Quality of Life among Tamil Speaking Adults Attending a
      Dental Institution in Chennai, Southern India.
AB  - INTRODUCTION: Oral Health-Related Quality of Life (OHRQoL) indicates an
      individual's perception of how their well-being and quality of life is influenced
      by oral health. It facilitates treatment planning, assessing patient centred
      treatment outcomes and satisfaction. AIM: The study aimed to identify the factors
      influencing OHRQoL among Tamil speaking South Indian adult population. MATERIALS
      AND METHODS: Non-probability sampling was done and 199 subjects aged 20-70 years
      were recruited for this observational study. The subjects were requested to fill
      a survey form along with the validated Tamil General Oral Health Assessment Index
      (GOHAI-Tml) questionnaire in the waiting area following which clinical
      examination was done by a single experienced Periodontist. RESULTS: The mean
      score with standard deviation for physical dimension was 4.34+/-0.96,
      psychological dimension was 4.03+/-1.13 and pain was 4.05+/-1.09 on GOHAI.
      Greater impacts were seen for psychosocial dimensions like pleased with the
      appearance of teeth/denture Q7 (3.7+/-1.2), worried about the problems with
      teeth/denture Q9 (3.7+/-1) and pain or discomfort in teeth Q12 (3.8+/-1).
      Functions like swallowing Q3 (4.5+/-0.8) and speaking Q4 (4.6+/-0.7) were
      minimally affected. As age increased subjects perceived more negative impacts as
      indicated by lower ADD-GOHAI and higher SC-GOHAI scores (p<0.01). Subjects
      complaining of bad breath, bleeding gums and Temporomandibular Joint (TMJ)
      problems, reported poor OHRQoL (p<0.05). It was observed that as self-perceived
      oral and general health status deteriorated, OHRQoL also worsened (p<0.01).
      Subjects with missing teeth, cervical abrasion, restorations, gingival recession
      and mobility had more impacts on OHRQoL (p<0.05). Subjects diagnosed with
      periodontitis had lower OHRQoL as reported on the scale than gingivitis subjects
      (p<0.01). CONCLUSION: In this study minimal impact was seen in all the three
      dimensions assessed with GOHAI. Factors like age, education, employment status,
      income, self-reported oral health, self-perceived general health, satisfaction
      with oral health, perceived need for treatment and denture wearing status
      influenced perceived OHRQoL. Bad breath, bleeding gums, TMJ problems, more number
      of missing teeth, decayed teeth, cervical abrasion, gingival recession and
      mobility were associated with poor OHRQoL.

PMID- 27891473
TI  - A Comparison of Conventional and Microwave Decalcification and Processing of
      Tooth and Mandibular Bone Specimens.
AB  - INTRODUCTION: Any laboratory procedure exposes the technician and the
      pathologists to the hazardous effects of chemicals. Conventional procedures like
      decalcification and histo-processing employed in laboratories are labour intense
      and time consuming thereby delaying the report dispatch. The present study was an
      attempt to employ a kitchen microwave to hasten the process and facilitate faster
      and accurate reporting; thus, benefitting the technician, pathologist and the
      patient. AIM: To compare conventional and microwave based decalci-fication,
      processing and staining of tooth and mandibular bone specimens using 5% nitric
      acid as decalcifying agent. MATERIALS AND METHODS: The sample included formalin
      fixed 180 tooth specimens (60 incisors, 60 premolars, 60 molars) and 60
      mandibular bone specimens (approx 0.5cm each). The hard tissue specimens were
      subjected to varying combination of conventional and microwave decalcification,
      processing and staining. The entire procedure was blinded and evaluated by two
      examiners. RESULTS: Conventional Decalcification (CD), processing and staining
      produced the utmost quality, though consuming a relatively longer duration.
      Microwave reduced the total decalcification time by half and retained the
      diagnostic quality of the specimens. On the contrary the microwave based
      processing and staining caused significant damage to the tissues rendering
      sections un-diagnostic. CONCLUSION: A combination of Microwave Decalcification
      (MD) followed by Conventional Processing (CP) and staining would be ideal to
      hasten the overall laboratory time with minimal compromise on tissue quality.

PMID- 27891474
TI  - An Evaluation of Use of Botulinum Toxin Type A in the Management of Dynamic
      Forehead Wrinkles - A Clinical Study.
AB  - INTRODUCTION: The pursuit of youth and beauty has undergone a resurgence of
      interest which is evidenced by increasing cosmetic procedures. Botulinum Toxin
      Type A (Botox) is one among the many procedures invented for facial rejuvenation
      which denervates certain muscles of facial expression responsible for facial
      wrinkles. It has been applied in the forehead, glabella, lateral canthal area and
      neck. In maxillofacial area hyperactive forehead wrinkles show sagging. AIM: This
      study was aimed to clinically evaluate the efficacy of Botox injection in the
      elimination of hyperdynamic forehead wrinkles and the objectives were to compare
      pre-operative and post-operative improvement in the number of wrinkles,
      photographic grading and patient satisfaction responses after 1st week, 4th week
      and 16th week. MATERIALS AND METHODS: A total of 10 patients were randomly
      included in the present study who were cooperative, motivated and aesthetically
      conscious with moderate to severe forehead wrinkles. Assessment was performed
      clinically, photographically (using standardized photographs) and patient
      satisfaction responses were recorded at 1st week, 4th week and 16th week.
      RESULTS: The study showed a significant difference in the elimination of wrinkles
      at rest and in action when assessed at 1st week and 4th week and it was
      consistent at 16th week. The patient showed positive satisfaction response
      without ptosis of the upper eyelid. CONCLUSION: Treatment with Botox is simple,
      safe and an effective modality for reduction of forehead wrinkles. It offers an
      alternative management in a cost-effective way when compared to surgical
      procedures.

PMID- 27891475
TI  - Self-Reported Obstacles to Regular Dental Care among Information Technology
      Professionals.
AB  - INTRODUCTION: Good oral health is important for an individual as well as social
      well-being. Occupational stress and work exhaustion in Information Technology
      (IT) professionals may influence the oral health and oral health related quality
      of life. AIM: To assess and compare self-reported obstacles for regular dental
      care and dental visits among IT professionals based on age, gender, dental
      insurance and working days per week. MATERIALS AND METHODS: A cross-sectional
      study was conducted among 1,017 IT professionals to assess the self-reported
      obstacles to regular oral health care in Hyderabad city, Telangana, India. The
      Dental Rejection of Innovation Scale (DRI-S) was employed in this study.
      Comparison between means of DRI-S based on variables was done using t-test and
      ANOVA. The association between variables and DRI-S was determined using Chi
      square test. RESULTS: A total of 1017 participants comprising of 574 (56%) males
      and 443 (44%) females participated in the study. As age increased, a significant
      increase in mean DRI-S scores was seen for total and individual domains except
      for the "Situational" domain wherein higher mean score (9.42+/-2.5; p=0.0006) was
      observed among 30-39 years age group. Even though females reported higher mean
      scores for total and individual domains when compared to males, nevertheless
      significant difference was seen only for total (p=0.03) and "Lack of Knowledge"
      (p=0.001) domain. CONCLUSION: Self-reported obstacles to regular dental care was
      more with increasing age, increased number of working days per week, irregular
      dental visits and absence of dental insurance facility.

PMID- 27891476
TI  - Anti bacterial Effectiveness of Electro- Chemically Activated (ECA) Water as a
      Root Canal Irrigant- An In-vitro Comparative Study.
AB  - INTRODUCTION: Sodium hypochlorite, is the irrigant of choice for many clinicians,
      but its strong toxic and damaging effects on vital periapical tissues is always a
      matter of concern. So, the search for a root canal irrigant with a broad
      antimicrobial spectrum yet with a limited toxicity on vital tissues is always
      desirable. AIM: The study evaluated antimicrobial efficacy of Electro-Chemically
      Activated (ECA) water as a root canal irrigant against E. faecalis. MATERIALS AND
      METHODS: Forty eight single rooted human teeth were decoronated to a length of
      15mm. All teeth were divided into four test groups (group A - ECA anolyte, group
      B - 1% sodium hypochlorite, group C - 3% sodium hypochlorite, group D - distilled
      water) of 12 each. Only 1ml of Ringer's solution and calibrated suspensio of E.
      faecalis was injected into each canal, aspirated and placed on agar plates and
      incubated aerobically at 37 degrees C for two days. The suspension was aspirated
      and spread onto the blood agar plate and incubated. All samples were irrigated
      with four test solutions and Brain Heart Infusion (BHI) solution was injected
      into each canal then aspirated and spread onto blood agar and incubated. After
      inoculations Colony Forming Unit (CFU) and optical density was measured under a
      microscope and spectrophotometer. The data obtained were statistically analysed
      by one way ANOVA and Dunkan's multiple range test. RESULTS: CFU reduction was not
      statistically significant between the test groups. The optical density showed
      statistically significant difference between the test groups (p<=0.001).
      CONCLUSION: The antimicrobial efficacy of ECA was found to be comparable to
      sodium hypochlorite solutions.

PMID- 27891478
TI  - Customized Modified Haas Palatal Expansion in Mixed Dentition: A Case Report.
AB  - The dental arch perimeter and transpalatal width are the most significant arch
      dimensions in the developing individuals. Its management during the primary,
      mixed and early permanent dentition are greatly important for the normal
      development of the dental arches and significantly improve the occlusion in
      adulthood. Malocclusion is a constant source of threat to the facial appearance.
      Severe anterior crowding and narrow maxillary arches adversely affect the smile,
      facial profile and consequently patient becomes handicapped socially as well as
      psychologically. Maxillary expansion has been used in resolving the problems of
      crowding, constricted arches and allow for forward growth of the mandible in
      growing children. This case report describes the use of a customized modified
      Haas appliance in intercepting the maxillary anterior crowding and gain the
      transpalatal width and arch perimeter of the maxilla, enhance the smile and
      facial profile and to allow the forward mandibular growth without any anterior
      occlusal interferences.

PMID- 27891477
TI  - Assessment of Periodontal Health Status in Smokers and Smokeless Tobacco Users: A
      Cross-Sectional Study.
AB  - INTRODUCTION: Oral smokeless tobacco consumption has been considered as a major
      risk factor for oral cancer, its role as a risk factor for periodontal disease is
      less well documented when compared to that of relationship between smoking and
      periodontal disease. AIM: The aim of the present cross-sectional study was to
      evaluate the effect of various forms of tobacco consumption i.e., smoking and
      smokeless tobacco forms on periodontal status. MATERIALS AND METHODS: The study
      population included 120 subjects with the habit of tobacco consumption, based on
      form of tobacco use they were divided into Group 1 (smoking), Group 2 (Smokeless
      tobacco), and Group 3 (smokers and smokeless tobacco users). The periodontal
      status for each group was evaluated by measuring Oral Hygiene Index- Simplified
      (OHI-S) and Community Periodontal Index (CPI) for Probing Depth (CPI-PD) and
      Attachment Loss (CPI-AL). RESULTS: OHI-S mean scores in Group 1 (3.53+/-1.03),
      Group 2 (3.06+/-0.92) and Group 3 (3.45+/-0.96) were similar, which were not
      statistically significant (p>0.076). The mean values of CPI-PD were 3.75+/-0.44
      in Group 1, 3.65+/-0.48 in Group 2, 3.80+/-0.41 in Group 3 with no significant
      difference between the three Groups (p> 0.309). When the mean values of CPI-AL
      (0.95+/-0.75 in Group 1, 1.40+/-0.74 in group 2, and 1.55+/-0.60 in Group 3) were
      compared in between the Groups, a statistically significant difference was
      observed in Group 3 (p<0.001). CONCLUSION: The results showed that tobacco
      consumption in both forms caused poor periodontal status, with smokeless tobacco
      users having more amount of attachment loss than smokers.

PMID- 27891479
TI  - Bilateral Three Rooted Mandibular Premolars and Four Rooted Mandibular First and
      Second Molar: A Rare Anatomical Variant.
AB  - The mandibular premolars and molars exhibit wide variations in the form of roots
      and root canals. A bilateral symmetry of three rooted mandibular first and second
      premolar and four rooted mandibular first and second molar in a same patient is a
      rare entity and one such case is presented in this case report.

PMID- 27891480
TI  - Traumatic Ulcerative Granuloma with Stromal Eosinophila: A Case Report and Review
      of Pathogenesis.
AB  - Traumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is an uncommon
      condition considered to be a, reactive benign lesion of the oral mucosa, usually
      affecting the tongue. Its aetiopathogenesis is still uncertain. However, trauma
      has been found to be a contributing factor in a majority of the cases.
      Clinically, it often presents as an isolated ulcer or an indurated submucosal
      mass. Microscopically, it is characterized by a diffuse polymorphic cell
      infiltrate composed predominantly of eosinophils, B and T lymphocytes,
      macrophages, and large atypical cells involving the superficial mucosa and
      extending deep into the submucosa causing degeneration of the underlying muscle.
      TUGSE is rare and may be easily mistaken for a cancer or microbial infection, but
      it is self-limiting and tends to resolve spontaneously. Thus, awareness of this
      entity is important to emphasize the correct diagnosis of indurated ulcerated
      lesions and deliver appropriate and effective treatment. The present case
      highlights the clinical aspects, aetiopathogenesis and histopathology of this
      uncommon lesion.

PMID- 27891481
TI  - A Large Pregnancy Tumor of Tongue - A Case Report.
AB  - Pyogenic granuloma is a tissue overgrowth which commonly develops as a response
      to irritation or trauma which is usually localized. Though gingiva is said to be
      the common site, it also can occur on lip, tongue and buccal mucosa. Pathogenesis
      is unclear but trauma, infection and hormonal imbalance are attributed as reasons
      for occurrence. Histologically this reactive lesion is filled with immature
      fibroblastic connective tissue, profilerative blood vessels and inflammatory
      cells. This article presents a case of a large pyogenic granuloma of the tongue
      which is a rare site for this tumor in a 27 year old woman.

PMID- 27891482
TI  - Treatment Emergent Agranulocytosis with Skin and Gingival Lesions in a Chronic
      Lymphocytic Leukemia Patient: A Case Report.
AB  - Chronic Lymphocytic Leukaemia (CLL) is a monoclonal lymphoid malignancy
      characterized by progressive accumulation of small, mature but functionally
      incompetent neoplastic lymphocytes in the peripheral blood, bone marrow and
      lymphoid organs. Patients present a variable course and may not require early
      intervention unlike other malignancies. Patients with rapidly deteriorating blood
      counts, and organomegaly need treatment. Alkylating agent live Bendamustine
      combined with Rituximab, anti-CD 20 monoclonal antibody have shown promising
      results in such patients. Anaemia, neutropenia and thrombocytopenia have been
      reported as treatment emergent events with this combination therapy. Neutrophils
      are the major innate defense and their depletion can result in a wide range of
      opportunistic infections. This case report discusess the oral and dermal lesions
      which emerged with the Rituximab and Bendamustine combination therapy in a
      patient with CLL and their management.

PMID- 27891483
TI  - Cystadenoma in Retromolar Region: A Case Report.
AB  - Cystadenoma is a rare benign salivary gland epithelial tumor that is
      characterized by intraluminal papillary projection. Majority of the tumors are
      located in minor salivary glands and usually occur in palatal and buccal mucosa,
      but rarely found in retromolar area. Clinically it is difficult to differentiate
      it from other minor salivary gland tumors, and diagnosis is chiefly based on
      characteristic clinical features and immunohistochemistry. We present a case of
      Cystadenoma arising from the minor salivary gland in retromolar area of a 44 year
      old female patient with a special emphasis on the immunohistochemistry to rule
      out the metastatic follicular carcinoma of thyroid.

PMID- 27891484
TI  - "Histiocytosis X" - A Rare Case Report.
AB  - Histiocytosis X is an idiopathic disease, characterized by a disorder of the
      reticulo-endothelial system in the human body. Histopathological studies carried
      out right from the 1800s have seen a significant similarity in the pathologic
      process of different stages in particular clinical syndromes showing
      proliferation of mature histiocytes. It was then modified by Lichenstein in 1953
      as "Histiocytosis X". The exact aetiology is unknown; hence, the name
      "Histiocytosis X". The disease classically presents with three syndromes namely
      Eosinophilic granuloma, Letterer-Siwe disease and Hand-Schuller-Christian
      disease. These syndromes present with a spectrum of clinical manifestations with
      histiocytic proliferation in the granulomatous lesion. The disease is neither
      familial nor hereditary, nor does it have any microbiological pathologic origin.
      This disease can be conservatively managed by antibiotics and steroids or
      surgical curettage with radiotherapy. We report a five-year-old male child who
      was incidentally diagnosed to have Histiocytosis X. This patient was managed with
      a moderate surgical procedure with total avoidance of radiotherapy. An adequate
      follow-up of this patient shows total regression of the lesion and good bone
      healing.

PMID- 27891485
TI  - Ameloblastic Carcinoma: A Report of Three Cases.
AB  - Malignant odontogenic tumours are rare and represent approximately 1% of all oral
      malignancies. Ameloblastic carcinoma is a rare odontogenic tumour, which is
      aggressive in nature with extensive local bone destruction that has retained the
      features of ameloblastic differentiation and also exhibits cytological features
      of malignancy. It occurs primarily in the mandible in a wide range of age groups.
      It may arise de-novo or in pre-existing ameloblastoma or odontogenic cyst. The
      purpose of this report is to present three cases of ameloblastic carcinoma with
      varying presentations as central and peripheral entities.

PMID- 27891486
TI  - Eosinophilic Granuloma Presenting as Palatal Swelling.
AB  - Swellings involving palate can be challenging to diagnose for the clinician as
      they have wide range of origin which can result from developmental, inflammatory,
      reactive or a neoplastic process. The clinical presentation of these swellings is
      similar and difficult to differentiate from each other. So it is important to
      take proper history from the patient and subject the patient to appropriate
      laboratory and radiographic investigations and finally biopsy is mandatory for
      accurate diagnosis. Thus, this article highlights on various common palatal
      swellings, their clinical presentation, and differential diagnosis helpful for
      proper diagnosis of swellings associated with palate.

PMID- 27891487
TI  - A Rare Case of Pyogenic Granuloma with a Natal Tooth.
AB  - Natal teeth are teeth present in the oral cavity at the time of birth. It is
      extremely rare to find natal teeth in association with pathological conditions of
      the oral cavity. Pyogenic granuloma is a type of inflammatory hyperplasia that
      appears as an over exuberant connective tissue response to a stimulus or injury,
      in the present case the injurious agent is the natal tooth. The parents of the
      eight day old male infant brought the child with a natal tooth associated with a
      soft tissue lesion growing from the gum pad. A provisional diagnosis of pyogenic
      granuloma was made on behalf of the clinical findings which were confirmed by
      histopathology. The natal tooth was extracted and the lesion was surgically
      excised. Complete healing of the gumpad took place after excision of the lesion
      and extraction of the natal tooth and the child was able to feed normally within
      a week. The purpose of this case report is that Pediatric Dentist should be aware
      of this rare unusual clinical presentation and plan for an appropriate treatment
      modality in order to avoid any future complications.

PMID- 27891488
TI  - Management of Recurrent Odontogenic Myxoma of Mandible: A Clinical Case Report.
AB  - Odontogenic Myxoma (OM) is a slow growing painless locally aggressive tumor seen
      in gnathic bones and is generally asymptomatic. OM is characterized by spindle,
      wedge or stellate shaped cells loosely arranged in an abundant mucoid stroma. It
      is found incidentally on radiographs and may vary from a unilocular radiolucency
      to a multilocular lesion with well-defined or diffuse margins. Treatment includes
      surgical management that may range from simple enucleation and curettage to
      surgical excision including peripheral osteotomy, segmental resection,
      hemimandibulectomy and maxillectomy. Here we are presenting a case report on
      odontogenic myxoma with recurrence after conservative treatment.

PMID- 27891490
TI  - Is Optimal Management of Recurrent Aphthous Stomatitis Possible? A Reality Check.
AB  - Recurrent Aphthous Stomatitis (RAS) is a condition in which aphthous ulcers
      repeatedly occur in the oral cavity. It is prevalent in developed countries,
      occurring in all ages, geographic regions and races and about 80% of people have
      one episode of oral aphthous ulcers before the age of 30 years. With no
      laboratory procedures to confirm the diagnosis, treatment is mainly empirical in
      nature and focuses on short-term symptomatic management. Although numerous
      treatment modalities have been recommended, only a few are evidence based and can
      be considered for the optimal management of RAS. Biologic agents are a new
      category of drugs which acts by blocking specific pathways associated with the
      pathophysiology of neoplastic or immune-mediated diseases. These agents have
      targeted immunosuppressive or anti-inflammatory actions. In patients of RAS who
      were not responding to standard therapy, etanercept, adalimumab, infliximab and
      Interferon-Alpha (INF-alpha) were found to be useful. The objective of this
      review was to propose and review a treatment protocol to be followed for the
      optimal management of RAS. We reviewed several evidence-based studies and through
      this review we recommend topical interventions as the first-line of therapy since
      they are associated with low risk of systemic side effects. Due to limitations in
      the number of evidence-based trials and the insufficient data to support or
      refute the efficacy of the therapies prescribed, larger evidence-based clinical
      studies and literature reviews are needed to further improvise the optimal
      methodology for the effective management of RAS.

PMID- 27891491
TI  - MRI in Dentistry- A Future Towards Radiation Free Imaging - Systematic Review.
AB  - INTRODUCTION: Magnetic Resonance Imaging (MRI), being a technique with huge
      potential, has become the primary diagnostic investigation for many clinical
      problems. Its application now has been successfully used in dentistry to maximize
      the diagnostic certainty. AIM: The present review aims to analyze the
      applicability, feasibility and efficacy of MRI in the field of dentistry.
      MATERIALS AND METHODS: A literature search was performed in main databases like
      Pub Med Central, Cochrane Library, Embase and Google Scholar from 1970 up to
      December 2015. The 2672 titles that appeared, 25 fulfilled the criteria and were
      included in the review. Two articles were hand searched and three articles
      through e-mail were also included. RESULTS: The review highlights the increasing
      role of MRI in dentistry. In the available literature, it was found that T1 and
      T2 weighted images were the acceptable diagnostic images for detection of dental
      related diseases. CONCLUSION: MRI can be used in diagnosis and treatment planning
      of implants, jaw lesions, diseases of Temporomandibular Joints (TMJ), orthodontic
      treatment, endodontic treatment etc., to achieve better prognosis.

PMID- 27891489
TI  - Techniques to Evaluate Dental Erosion: A Systematic Review of Literature.
AB  - This article reviews different techniques for evaluating dental erosion, weighs
      the advantages and disadvantages of these techniques, and presents the latest
      trends in the study of dental erosion. In May 2014, an initial search was carried
      out in the PubMed/MEDLINE database of indexed journals from 1975 to 2013 using
      the following keywords: dental erosion; dental erosion In-vitro; and dental
      erosion in-vivo. Bibliographic citations from the papers found were then used to
      find other useful sources. The authors categorize the techniques into three
      classes: in-vitro, in-vivo and in-vitro/in-vivo. The article discusses the
      instrumentation required to use each of these techniques, as well as their
      rationale, merits and applications. The emergence of in-vitro/in-vivo techniques
      offers the potential to accurately quantify tooth wear in clinical situations.
      Cross-sectional as well as longitudinal studies show that these techniques will
      improve diagnosis, treatment planning and management of dental erosion.

PMID- 27891493
TI  - Mohr-Claussen Syndrome: A Rare Case.

PMID- 27891492
TI  - Effect of Magnetic Field on Bone Healing around Endosseous Implants - An In-vivo
      Study.
AB  - INTRODUCTION: After implant placement, a stress-free healing period of 3-6 months
      is a pre-requisite to achieve good osseointegration. If this duration could be
      reduced, the patients would feel happier. Eventhough, immediate loading of
      implants is a clinically feasible concept; it is not possible in certain
      situations. Few studies have shown that Static magnetic field is useful to
      promote bone formation faster after the bone is wounded. AIM: This pilot study
      was intended to evaluate the tissue response after implant placement under the
      influence of magnetic field. MATERIALS AND METHODS: Twenty Tidal Spiral implants
      were used for this study. Two implants were placed in each patient in the
      anterior mandible corresponding to the B and D regions and the implant on the D
      region was exposed to magnetic field using safer magnet (Neodymium Boron Iron)
      and the implant on the B region served as a control. Both the implants were
      compared for stability using Resonance Frequency Analyzer (RFA) at Days 0, 30, 60
      and 90. Mean Implant Stability Quotient (ISQ) values were compared on both sides
      using student's paired t-test and repeated measures ANOVA (analysis of variance).
      There was a significant difference in the mean ISQ values, hence, a post-hoc test
      was done to evaluate whether there is any difference between the follow-ups.
      RESULTS: The average ISQ value for implants at 0 day in the B and D regions was
      68.6 and 68.7 respectively. The average ISQ value at 30th day, 60th day and 90th
      day was 73.25, 76.05 and 78.95 respectively on the magnetic side (D region).
      Whereas on the non-magnetic side (B region) at 30th day, 60th day and 90th day
      was 68.45, 72.05 and 74.45 respectively. CONCLUSION: The implant stability
      quotient values obtained on the magnetic side were significantly greater than on
      the non-magnetic side. Positive correlation exists between the magnetic field and
      osseointegration.

PMID- 27891494
TI  - Modified Distal Shoe Appliance for Multiple Loss of First and Second Primary
      Molars.

PMID- 27891495
TI  - Proliferative Verrucous Leukoplakia - A Perpetuating Ambiguity.

PMID- 27891496
TI  - Interpositional Gap Arthroplasty by Versatile Pedicled Temporalis Myofascial Flap
      in the Management of Temporomandibular Joint Ankylosis- A Case Series Study.
AB  - Temporomandibular Joint (TMJ) ankylosis is a situation in which the mandibular
      condyle is fused to the glenoid fossa by bone or fibrous tissue. The management
      of TMJ ankylosis has a complicated chore and it is challenging for the
      maxillofacial surgeon because of technical hitches and high rate of re-ankylosis.
      Interpositional gap arthroplasty is one of the modalities for its management. A
      range of inter-positional materials have been used to avert recurrence after gap
      arthroplasty in TMJ ankylosis. The aim of this series was to evaluate the
      effectiveness of the temporomyofacial flap in the treatment of TMJ ankylosis as
      an interpositional gap arthroplasty. A total of 10 cases with unilateral TMJ
      ankylosis were treated by interpositional gap arthroplasty by pedicled temporalis
      myofacial flap and evaluated with a follow-up of 6 months to 5 years (Mean 3.3
      years) for the functional stability of TMJ. All the patients were successfully
      treated. There were no signs of recurrence in any patients up to last follow up
      visit. The result showed that temporalis myofascial flap is a preferable choice
      for inter-positional gap arthroplasty which proves its versatility as an inter
      positional material.

PMID- 27891498
TI  - The Participation Patterns of Youth with Down Syndrome.
AB  - PURPOSE: The purpose of this paper was to investigate the participation patterns
      of children with Down syndrome (DS) using the construct of participation as
      defined by the International Classification of Functioning Disability and Health
      (ICF). METHODS: Sixty-two children with DS were recruited between the ages of 9
      and 17 years. All participants were given an interview-administered version of
      the Children's Assessment of Participation and Enjoyment (CAPE) to measure
      participation (1). RESULTS: Children with DS participated the most often, based
      on frequency, in recreational activities (p < 0.001); social activity types
      represented the greatest extension into the community based on with whom the
      children participated with (p < 0.05); finally, physical and social activities
      represented the greatest extension into the community geographically (p < 0.001).
      In addition, children with DS are significantly more active in activities that
      are informal in nature. CONCLUSION: Children with DS participate in a number of
      activities; however, the extent of their participation within these activities
      differs depending on the participation pattern examined. Implications for
      educational and community-based programs are discussed.

PMID- 27891497
TI  - Mechanisms involved in altered bone metabolism in diabetes: a narrative review.
AB  - Many studies have shown that change in metabolism caused by diabetes can
      influence the bone metabolism in a way that quality and strength of bone is
      decreased. A 6 times and 2 times increased risk of fracture is reported in
      patients with type 1 and type 2 diabetes, respectively. There are several
      mechanisms by which diabetes can affect the bone. The fact that some of these
      mechanisms are acting in opposite ways opens the door for debate on pathways by
      which diabetes affects the bones. On the other hand, bone is not a simple organ
      that only get influence from other organs, but it is an endocrine organ that by
      secreting the agents such as osteocalcin, adiponectin and visfatin which can
      affect the insulin sensitivity and metabolism. In this paper we tried to briefly
      assess the latest finding in this matter.

PMID- 27891499
TI  - A Presumptive Case of Human Rabies: A Rare Survived Case in Rural Ghana.
AB  - Rabies remains endemic in Ghana and continues to pose a major public health
      threat to humans and animals with a nearly 100% case fatality rate in humans. We
      report of a presumptive case of human rabies whose survival represents a rare
      occurrence in rural Ghana and worldwide. Lessons from this case study provide a
      critically needed focus in helping improve rabies surveillance and case
      management in Ghana. We report of the survival of a 36-year-old man who developed
      clinical rabies after he was bitten by his dog, while restraining the dog with a
      chain. Prior to this, he did not observe any abnormal or rabid behavior in the
      dog. Following the bite, he did not immediately resort to hospital treatment, but
      rather to traditional application of herbs to the laceration he sustained after
      the bite. The reason given for not seeking immediate hospital treatment was that
      the dog was not rabid and lack of funds to seek hospital care. However, after 10
      days he began to show symptoms of confusion, hydrophobia, and photophobia,
      consistent with rabies virus infection, and was subsequently rushed to the
      hospital by relatives. At the hospital, he was administered human immune tetanus
      immunoglobulin, diazepam, ceftriaxone, paracetamol, and intravenous fluids. No
      rabies vaccine was administered. Six days after commencing treatment, the patient
      became well, showed neither signs of confusional state, hydrophobia, nor
      photophobia. He was discharged home after 13 days of commencing treatment. This
      study provides insight on a presumptive case of human rabies that survived
      despite non-administration of rabies vaccine after exposure. It also exposes the
      weaknesses in the health and veterinary systems in rural Ghana regarding rabies
      surveillance and case management.

PMID- 27891500
TI  - Interspecies Communication between Pathogens and Immune Cells via Bacterial
      Membrane Vesicles.
AB  - The production of extracellular vesicles is a universal mechanism for
      intercellular communication that is conserved across kingdoms. Prokaryotes
      secrete 50-250 nm membrane vesicles (MVs) in a manner that is regulated by
      environmental stress and is thought to promote survival. Since many types of host
      derived stress are encountered during infection, this implies an important role
      for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram
      positive and gram-negative pathogens contain toxins, virulence factors, and other
      molecules that promote survival in the host. However, recent studies have also
      shown that bacterial MVs are enriched for molecules that stimulate innate and
      adaptive immune responses. As an example, MVs may serve multiple, important roles
      in regulating the host response to Mycobacterium tuberculosis (Mtb), an
      intracellular pathogen that infects lung macrophages and resides within modified
      phagosomes. Previously, we demonstrated that Mtb secretes MVs during infection
      that may modulate infected and uninfected immune cells. Our present data
      demonstrates that Mtb MVs inhibit the functions of macrophages and T cells, but
      promote Major Histocompatibility Complex (MHC) class II antigen presentation by
      dendritic cells. We conclude that bacterial MVs serve dual and opposing roles in
      the activation of and defense against host immune responses to Mtb and other
      bacterial pathogens. We also propose that MV secretion is a central mechanism for
      interspecies communication between bacteria and host cells during infection.

PMID- 27891501
TI  - Septins and Bacterial Infection.
AB  - Septins, a unique cytoskeletal component associated with cellular membranes, are
      increasingly recognized as having important roles in host defense against
      bacterial infection. A role for septins during invasion of Listeria monocytogenes
      into host cells was first proposed in 2002. Since then, work has shown that
      septins assemble in response to a wide variety of invasive bacterial pathogens,
      and septin assemblies can have different roles during the bacterial infection
      process. Here we review the interplay between septins and bacterial pathogens,
      highlighting septins as a structural determinant of host defense. We also discuss
      how investigation of septin assembly in response to bacterial infection can yield
      insight into basic cellular processes including phagocytosis, autophagy, and
      mitochondrial dynamics.

PMID- 27891503
TI  - TP53 Gene Status Affects Survival in Advanced Mycosis Fungoides.
AB  - TP53 is frequently mutated in different types of neoplasms including leukemia and
      lymphomas. Mutations of TP53 have also been reported in mycosis fungoides (MF),
      the most common type of cutaneous lymphoma. However, little is known about the
      frequency, spectrum of mutations, and their prognostic significance in MF. In
      this study, we have optimized the protocol for Sanger sequencing of TP53 using
      DNA extracted from archival paraffin-embedded biopsies. Of 19 samples from
      patients with stage IIB MF or higher, 31% harbored mutations in TP53. Overall
      survival of the patients with mutated TP53 was significantly shorter than median
      survival in the age- and stage-matched patients treated in our Institution.
      Distribution of mutations was heterogenous in TP53 exons; however, C > T
      transitions were common suggesting the causal role of ultraviolet radiation. We
      propose that TP53 mutation status would be useful for risk stratification of
      patients with advanced MF.

PMID- 27891504
TI  - Thoracic Aorta Aneurysm Repair in a Patient with a Solitary Kidney: Hybrid
      Surgery as a Bailout Procedure.
AB  - Thoracic endovascular aortic repair (TEVAR) is an emerging treatment option for
      thoracic aorta aneurysms (TAA). Endovascular access is a challenge. We present a
      novel TEVAR technique in a patient with single kidney and a 6.4 cm TAA.
      Attempting to place a sheath through iliac arteries was unsuccessful. The
      decision to proceed to hybrid TEVAR was made. The protection of the solitary
      kidney was achieved through axillo-femoral bypass, followed by an end-to-side
      anastomosis between the aorta and a bifurcated graft. Through the graft, a stent
      was introduced in the thoracic aorta. With the use of contrast material, the
      right position of the graft was confirmed.

PMID- 27891502
TI  - Diacylglycerol Kinases in T Cell Tolerance and Effector Function.
AB  - Diacylglycerol kinases (DGKs) are a family of enzymes that regulate the relative
      levels of diacylglycerol (DAG) and phosphatidic acid (PA) in cells by
      phosphorylating DAG to produce PA. Both DAG and PA are important second
      messengers cascading T cell receptor (TCR) signal by recruiting multiple effector
      molecules, such as RasGRP1, PKCtheta, and mTOR. Studies have revealed important
      physiological functions of DGKs in the regulation of receptor signaling and the
      development and activation of immune cells. In this review, we will focus on
      recent progresses in our understanding of two DGK isoforms, alpha and zeta, in
      CD8 T effector and memory cell differentiation, regulatory T cell development and
      function, and invariant NKT cell development and effector lineage
      differentiation.

PMID- 27891506
TI  - Synchronization of Dairy Cows Does Not Limit the Behavioral Response to Treatment
      in Mixed Treatment Experimental Designs.
AB  - In many research studies, animals assigned to different treatments are housed
      adjacently or together in a group. One critique of these designs has been the
      potential role of behavioral facilitation and synchronization between animals on
      different treatments in mixed treatment groups (heterogeneous groups). To
      evaluate this, we compared the synchrony of feeding behavior between dairy cows
      housed in heterogeneous groups to cows exposed to the same treatment
      simultaneously (homogenous groups). Twenty-four cows were exposed to each of the
      two treatments over 21 days in a replicated cross-over design. Treatments were
      two different schedules of timing of feed delivery: (A) feeding at milking time
      and (B) feeding halfway between milking times. For the last 7 days of each
      treatment period, feeding behavior was recorded electronically. Kappa
      coefficients were calculated for each animal within each group, as an estimate of
      agreement that any two cows within a group (i.e., each individual and each other
      cow in her group) would both be engaged in feeding activity for any hour of the
      day. The level of synchrony was similar for cows within homogenous groups (kappa
      = 0.31 +/- 0.030) compared with cows on the same treatment within heterogeneous
      groups (kappa = 0.32 +/- 0.037). Within heterogeneous groups, cows on the same
      treatment were nearly 50% more synchronized with each other than with those on
      the other treatment (kappa = 0.22 +/- 0.029). These results suggest that
      synchronization of feeding behavior does not restrict our ability to impose
      different treatments on individual cows within a group.

PMID- 27891505
TI  - Comparative Genomics of the Conjugation Region of F-like Plasmids: Five Shades of
      F.
AB  - The F plasmid is the foremost representative of a large group of conjugative
      plasmids, prevalent in Escherichia coli, and widely distributed among the
      Enterobacteriaceae. These plasmids are of clinical relevance, given their
      frequent association with virulence determinants, colicins, and antibiotic
      resistance genes. Originally defined by their sensitivity to certain male
      specific phages, IncF plasmids share a conserved conjugative system and
      regulatory circuits. In order to determine whether the genetic architecture and
      regulation circuits are preserved among these plasmids, we analyzed the natural
      diversity of F-like plasmids. Using the relaxase as a phylogenetic marker, we
      identified 256 plasmids belonging to the IncF/ MOBF12group, present as complete
      DNA sequences in the NCBI database. By comparative genomics, we identified five
      major groups of F-like plasmids. Each shows a particular operon structure and
      alternate regulatory systems. Results show that the IncF/MOBF12 conjugation gene
      cluster conforms a diverse and ancient group, which evolved alternative
      regulatory schemes in its adaptation to different environments and bacterial
      hosts.

PMID- 27891507
TI  - Improved Separations of Proteins and Sugar Derivatives Using the Small-Scale
      Cross-Axis Coil Planet Centrifuge with Locular Multilayer Coiled Columns.
AB  - 1 BACKGROUND: Countercurrent chromatography (CCC) is liquid-liquid partition
      chromatography without using a solid support matrix. This technique requires
      further improvement of partition efficiency and shortening theseparation time. 2
      METHODS: The locular multilayer coils modified with and without mixer glass beads
      were developed for the separation of proteins and 4-methylumbelliferyl (MU) sugar
      derivatives using the small-scale cross-axis coil planet centrifuge. 3 RESULTS:
      Proteins were well separated from each other and the separation was improved at a
      low flow rate of the mobile phase. On the other hand, 4-MU sugar derivatives were
      sufficiently resolved with short separation time at a highflow rate of the mobile
      phase under satisfactory stationary phase retention. 4 CONCLUSION: Effective
      separations were achieved using the locular multilayer coil for proteins with
      aqueous-aqueous polymer phase systems and for 4-MU sugar derivatives with organic
      aqueous two-phase solvent systems by inserting a glass bead into each locule.

PMID- 27891508
TI  - Effect of Water Activity and Packaging Material on the Quality of Dehydrated Taro
      (Colocasia esculenta (L.) Schott) Slices during Accelerated Storage.
AB  - The quality of dehydrated taro slices in accelerated storage (45 degrees C and
      75% RH) was determined as a function of initial water activity (aw) and package
      type. Color, rehydration capacity, thiamin content, and alpha-tocopherol content
      were monitored during 34 weeks of storage in polyethylene and foil laminate
      packaging at initial storage aw of 0.35 to 0.71. Initial aw at or below 0.54
      resulted in less browning and higher rehydration capacity, but not in
      significantly higher alpha-tocopherol retention. Foil laminate pouches resulted
      in a higher rehydration capacity and increased thiamin retention compared to
      polyethylene bags. Type of packaging had no effect on the color of the samples.
      Product stability was highest when stored in foil laminate pouches at 0.4aw.
      Sensory panels were held to determine the acceptability of rehydrated taro slices
      using samples representative of the taro used in the analytical tests. A hedonic
      test on rehydrated taro's acceptability was conducted in Fiji, with panelists
      rating the product an average of 7.2 +/- 1.5 on a discrete 9-point scale. Using a
      modified Weibull analysis (with 50% probability of product failure), it was
      determined that the shelf life of dehydrated taro stored at 45 degrees C was 38.3
      weeks.

PMID- 27891509
TI  - The Performance of Short-Term Heart Rate Variability in the Detection of
      Congestive Heart Failure.
AB  - Congestive heart failure (CHF) is a cardiac disease associated with the
      decreasing capacity of the cardiac output. It has been shown that the CHF is the
      main cause of the cardiac death around the world. Some works proposed to
      discriminate CHF subjects from healthy subjects using either electrocardiogram
      (ECG) or heart rate variability (HRV) from long-term recordings. In this work, we
      propose an alternative framework to discriminate CHF from healthy subjects by
      using HRV short-term intervals based on 256 RR continuous samples. Our framework
      uses a matching pursuit algorithm based on Gabor functions. From the selected
      Gabor functions, we derived a set of features that are inputted into a hybrid
      framework which uses a genetic algorithm and k-nearest neighbour classifier to
      select a subset of features that has the best classification performance. The
      performance of the framework is analyzed using both Fantasia and CHF database
      from Physionet archives which are, respectively, composed of 40 healthy
      volunteers and 29 subjects. From a set of nonstandard 16 features, the proposed
      framework reaches an overall accuracy of 100% with five features. Our results
      suggest that the application of hybrid frameworks whose classifier algorithms are
      based on genetic algorithms has outperformed well-known classifier methods.

PMID- 27891510
TI  - Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing
      Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways.
AB  - Objectives. To investigate the protective effects of tropisetron on acetaminophen
      (APAP-) induced liver injury in a mice model. Methods. C57BL/6 male mice were
      given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of
      acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP
      intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione
      (GSH), and superoxide dismutase (SOD) activities, and liver histopathological
      changes were examined. The MAP kinases were also detected by western blotting.
      Results. Our results showed that tropisetron pretreatment significantly
      attenuated the acute elevations of the liver enzyme ALT level, hepatic MPO
      activity, and hepatocytes necrosis in a dose-dependent manner (0.3-10 mg/kg) in
      APAP-induced hepatotoxicity mice. Tropisetron (1 and 3 mg/kg) suppressed APAP
      induced hepatic lipid peroxidation expression and alleviated GSH and SOD
      depletion. Administration of tropisetron also attenuated the phosphorylation of c
      Jun-NH2-terminal protein kinase (JNK) and extracellular signal-regulated kinase
      (ERK) caused by APAP. Conclusion. Our data demonstrated that tropisetron's
      hepatoprotective effect was in part correlated with the antioxidant, which were
      mediated via JNK and ERK pathways on acetaminophen-induced liver injury in mice.

PMID- 27891511
TI  - Diagnostic Value of CT Arthrography for Evaluation of Osteochondral Lesions at
      the Ankle.
AB  - Background. To retrospectively determine the diagnostic value of computed
      tomography arthrography (CTA) of the ankle in the evaluation of (osteo)chondral
      lesions in comparison to conventional magnetic resonance imaging (MRI) and
      intraoperative findings. Methods. A total of N = 79 patients had CTAs and MRI of
      the ankle; in 17/79 cases surgical reports with statements on cartilage integrity
      were available. Cartilage lesions and bony defects at talus and tibia were scored
      according to defect depth and size by two radiologists. Statistical analysis
      included sensitivity analyses and Cohen's kappa calculations. Results. On CTA,
      41/79 and 31/79 patients had full thickness cartilage defects at the talus and at
      the tibia, respectively. MRI was able to detect 54% of these defects. For the
      detection of full thickness cartilage lesions, interobserver agreement was
      substantial (0.72 +/- 0.05) for CTA and moderate (0.55 +/- 0.07) for MRI. In
      surgical reports, 88-92% and 46-62% of full thickness defects detected by CTA and
      MRI were described. CTA findings changed the further clinical management in 15.4%
      of cases. Conclusions. As compared to conventional MRI, CTA improves detection
      and visualization of cartilage defects at the ankle and is a relevant tool for
      treatment decisions in unclear cases.

PMID- 27891512
TI  - A De-O-acylated Lipooligosaccharide-Based Adjuvant System Promotes Antibody and
      Th1-Type Immune Responses to H1N1 Pandemic Influenza Vaccine in Mice.
AB  - Vaccine adjuvants are agents that are used to promote immune responses to vaccine
      antigens and thereby to enhance the protective efficacy of the vaccines. In this
      study, we investigated the adjuvant activity of CIA06, an adjuvant system that is
      composed of a toll-like receptor 4 agonist de-O-acylated lipooligosaccharide
      (dLOS) and aluminum hydroxide, on the H1N1 pandemic influenza vaccine Greenflu
      S(r) in mice. CIA06 significantly enhanced influenza-specific serum IgG,
      hemagglutination-inhibition, and virus-neutralizing antibody titers, which
      eliminated vaccine dose-dependency in the antibody response. Mice immunized with
      the CIA06-adjuvanted Greenflu-S showed Th1-type-predominant cytokine profiles,
      and both CD4+ and CD8+ T cell responses were induced. Immunization of mice with
      the CIA06-adjuvanted vaccine reduced the mortality and morbidity of mice upon
      lethal challenges with influenza virus, and no excessive inflammatory responses
      were observed in the lung tissues of the immunized mice after viral infection.
      These data suggest that the dLOS-based adjuvant system CIA06 can be used to
      promote the immune responses to influenza vaccine or to spare antigen dose
      without causing harmful inflammatory responses.

PMID- 27891513
TI  - Clinic Predictive Factors for Insufficient Myocardial Reperfusion in ST-Segment
      Elevation Myocardial Infarction Patients Treated with Selective Aspiration
      Thrombectomy during Primary Percutaneous Coronary Intervention.
AB  - Background. Insufficient data are available on the potential benefit of selective
      aspiration and clinical predictors for no-reflow in STEMI patients undergoing
      primary percutaneous coronary intervention (PPCI) adjunct with aspiration
      thrombectomy. Objective. The aim of our study was to investigate clinical
      predictors for insufficient reperfusion in patients with high thrombus burden
      treated with PPCI and manual aspiration thrombectomy. Methods. From January 2011
      till December 2015, 277 STEMI patients undergoing manual aspiration thrombectomy
      and PPCI were selected and 202 patients with a Thrombolysis in Myocardial
      Infarction (TIMI) thrombus grade 4~5 were eventually involved in our study.
      According to a cTFC value, patients were divided into Group I (cTFC > 40),
      namely, insufficient reperfusion group; Group II (cTFC <= 40), namely, sufficient
      reperfusion group. Results. Univariate analysis showed that hypertension,
      multivessel disease, time from symptom to PCI (?4.8 hours), and postaspiration
      cTFC > 40 were negative predictors for insufficient reperfusion. After
      multivariate adjustment, age ? 60 years, hypertension, time from symptom to PCI
      (?4.8 hours), and postaspiration cTFC > 40 were independently associated with
      insufficient reperfusion in STEMI patients treated with manual aspiration
      thrombectomy. Upfront intracoronary GP IIb/IIIa inhibitor (Tirofiban) was
      positively associated with improved myocardial reperfusion. Conclusion. Fully
      identifying risk factors will help to improve the effectiveness of selective
      thrombus aspiration.

PMID- 27891515
TI  - The Association between VDR Gene Polymorphisms and Diabetic Retinopathy
      Susceptibility: A Systematic Review and Meta-Analysis.
AB  - Aims. Studies on the associations of vitamin D receptor (VDR) gene polymorphisms
      with diabetic retinopathy (DR) susceptibility reported conflicting results. A
      systematic meta-analysis was undertaken to clarify this topic. Methods. A
      systematic search of electronic databases (PubMed, EMBASE, and CNKI) was carried
      out until March 31, 2016. The pooled odds ratio (OR) and 95% confidence interval
      (CI) were used to assess the strength of the association. Results. A total of 7
      studies fulfilling the inclusion criteria were included in this meta-analysis
      (649 cases and 707 controls). Pooled ORs showed a significant association between
      FokI polymorphism and DR risk in all the four genetic models (OR = 1.612
      (1.354~1.921), 1.988 (1.481~2.668), 1.889 (1.424~2.505), and 2.674 (1.493~4.790)
      in allelic, dominant, recessive, and additive models, resp., PZ < 0.01), but not
      for TaqI or BsmI polymorphism (PZ > 0.05). Similar results were found in the
      subgroup analysis. Sensitivity analysis indicated that the results were
      relatively stable and reliable. Results of Begg's and Egger's tests suggested a
      lack of publication bias. Conclusions. Our meta-analysis demonstrated that DR was
      significantly associated with VDR gene FokI polymorphism. However, due to the
      relatively small sample size in this meta-analysis, further studies with a larger
      sample size should be done to confirm the findings.

PMID- 27891516
TI  - Functional Region Annotation of Liver CT Image Based on Vascular Tree.
AB  - Anatomical analysis of liver region is critical in diagnosis and treatment of
      liver diseases. The reports of liver region annotation are helpful for doctors to
      precisely evaluate liver system. One of the challenging issues is to annotate the
      functional regions of liver through analyzing Computed Tomography (CT) images. In
      this paper, we propose a vessel-tree-based liver annotation method for CT images.
      The first step of the proposed annotation method is to extract the liver region
      including vessels and tumors from the CT scans. And then a 3-dimensional thinning
      algorithm is applied to obtain the spatial skeleton and geometric structure of
      liver vessels. With the vessel skeleton, the topology of portal veins is further
      formulated by a directed acyclic graph with geometrical attributes. Finally,
      based on the topological graph, a hierarchical vascular tree is constructed to
      divide the liver into eight segments according to Couinaud classification theory
      and thereby annotate the functional regions. Abundant experimental results
      demonstrate that the proposed method is effective for precise liver annotation
      and helpful to support liver disease diagnosis.

PMID- 27891514
TI  - Evidence for a "Pathogenic Triumvirate" in Congenital Hepatic Fibrosis in
      Autosomal Recessive Polycystic Kidney Disease.
AB  - Autosomal recessive polycystic kidney disease (ARPKD) is a severe monogenic
      disorder that occurs due to mutations in the PKHD1 gene. Congenital hepatic
      fibrosis (CHF) associated with ARPKD is characterized by the presence of hepatic
      cysts derived from dilated bile ducts and a robust, pericystic fibrosis. Cyst
      growth, due to cyst wall epithelial cell hyperproliferation and fluid secretion,
      is thought to be the driving force behind disease progression. Liver fibrosis is
      a wound healing response in which collagen accumulates in the liver due to an
      imbalance between extracellular matrix synthesis and degradation. Whereas both
      hyperproliferation and pericystic fibrosis are hallmarks of CHF/ARPKD, whether or
      not these two processes influence one another remains unclear. Additionally,
      recent studies demonstrate that inflammation is a common feature of CHF/ARPKD.
      Therefore, we propose a "pathogenic triumvirate" consisting of hyperproliferation
      of cyst wall growth, pericystic fibrosis, and inflammation which drives CHF/ARPKD
      progression. This review will summarize what is known regarding the mechanisms of
      cyst growth, fibrosis, and inflammation in CHF/ARPKD. Further, we will discuss
      the potential advantage of identifying a core pathogenic feature in CHF/ARPKD to
      aid in the development of novel therapeutic approaches. If a core pathogenic
      feature does not exist, then developing multimodality therapeutic approaches to
      target each member of the "pathogenic triumvirate" individually may be a better
      strategy to manage this debilitating disease.

PMID- 27891517
TI  - Prognostic Significance of Preoperative Neutrophil-to-Lymphocyte Ratio in
      Nonmetastatic Renal Cell Carcinoma: A Large, Multicenter Cohort Analysis.
AB  - Background. The prognostic significance of the neutrophil-to-lymphocyte ratio
      (NLR) in nonmetastatic renal cell carcinoma (non-mRCC) is controversial, although
      NLR has been established as a prognostic factor in several cancers. The objective
      of our study was to assess the prognostic significance of preoperative NLR in non
      mRCC, based on a large, multicenter cohort analysis. Methods. Totally, 1,284 non
      mRCC patients undergoing surgery were enrolled from six institutions between 2000
      and 2014. Recurrence-free survival (RFS) and cancer-specific survival (CSS) were
      calculated, and the prognostic significance of NLR was evaluated. Results.
      Patients with higher NLR had larger tumors (p < 0.001), higher T stage (p <
      0.001), worse Eastern Cooperative Oncology Group performance status (p < 0.001),
      worse symptoms (p = 0.003), sarcomatoid differentiation (p = 0.004), and tumor
      necrosis (p < 0.001). The 5-year RFS and CSS rates were significantly lower in
      patients with high NLR than in those with low NLR (each p < 0.001). Multivariate
      analysis identified NLR to be an independent predictor of RFS and CSS (each p <
      0.05). Moreover, predictive accuracy of multivariate models for RFS and CSS
      increased by 2.2% and 4.2%, respectively, with NLR inclusion. Conclusions. Higher
      NLR was associated with worse clinical behavior of non-mRCC. Also, NLR was a
      significant prognostic factor of both RFS and CSS.

PMID- 27891518
TI  - Size and Proportions of Slow-Twitch and Fast-Twitch Muscle Fibers in Human Costal
      Diaphragm.
AB  - Smaller diaphragmatic motor unit potentials (MUPs) compared to MUPs of limb
      muscles lead to the hypothesis that diaphragmatic muscle fibers, being the
      generators of MUPs, might be also smaller. We compared autopsy samples of costal
      diaphragm and vastus lateralis of healthy men with respect to fibers' size and
      expression of slow myosin heavy chain isoform (MyHC-1) and fast 2A isoform (MyHC
      2A). Diaphragmatic fibers were smaller than fibers in vastus lateralis with
      regard to the mean minimal fiber diameter of slow-twitch (46.8 versus 72.2 MUm, p
      < 0.001), fast-twitch (45.1 versus 62.4 MUm, p < 0.001), and hybrid fibers (47.3
      versus 65.0 MUm, p < 0.01) as well as to the mean fiber cross-sectional areas of
      slow-twitch (2376.0 versus 5455.9 MUm2, p < 0.001), fast-twitch (2258.7 versus
      4189.7 MUm2, p < 0.001), and hybrid fibers (2404.4 versus 4776.3 MUm2, p < 0.01).
      The numerical proportion of slow-twitch fibers was higher (50.2 versus 36.3%, p <
      0.01) in costal diaphragm and the numerical proportion of fast-twitch fibers
      (47.2 versus 58.7%, p < 0.01) was lower. The numerical proportion of hybrid
      fibers did not differ. Muscle fibers of costal diaphragm have specific
      characteristics which support increased resistance of diaphragm to fatigue.

PMID- 27891519
TI  - Advances in Colorectal Cancer.

PMID- 27891520
TI  - Short-Term Lifestyle Strategies for Sustaining Cognitive Status.
AB  - Cognitive decline impacts older adults, particularly their independence. The goal
      of this project was to increase understanding of how short-term, everyday
      lifestyle options, including physical activity, help an older adult sustain
      cognitive independence. Using a secondary analysis of lifestyle choices, we drew
      on a dataset of 4,620 community-dwelling elders in the US, assessed at baseline
      and one year later using 2 valid and reliable tools, the interRAI Community
      Health Assessment and the interRAI Wellness tool. Decline or no decline on the
      Cognitive Performance Scale was the dependent variable. We examined sustaining
      one's status on this measure over a one-year period in relation to key dimensions
      of wellness through intellectual, physical, emotional, social, and spiritual
      variables. Engaging in physical activity, formal exercise, and specific
      recreational activities had a favorable effect on short-term cognitive decline.
      Involvement with computers, crossword puzzles, handicrafts, and formal education
      courses also were protective factors. The physical and intellectual domains of
      wellness are prominent aspects in protection from cognitive decline. Inherent in
      these two domains are mutable factors suitable for targeted efforts to promote
      older adult health and well-being.

PMID- 27891521
TI  - Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain.
AB  - Neuropathic pain, defined as pain caused by a lesion or disease of the
      somatosensory nervous system, is characterized by dysesthesia, hyperalgesia, and
      allodynia. The number of patients with this type of pain has increased rapidly in
      recent years. Yet, available neuropathic pain medicines have undesired side
      effects, such as tolerance and physical dependence, and do not fully alleviate
      the pain. The mechanisms of neuropathic pain are still not fully understood.
      Injury causes inflammation and immune responses and changed expression and
      activity of receptors and ion channels in peripheral nerve terminals.
      Additionally, neuroinflammation is a known factor in the development and
      maintenance of neuropathic pain. During neuropathic pain development, the C-C
      motif chemokine receptor 2 (CCR2) acts as an important signaling mediator.
      Traditional plant treatments have been used throughout the world for treating
      diseases. We and others have identified food-derived compounds that alleviate
      neuropathic pain. Here, we review the natural compounds for neuropathic pain
      relief, their mechanisms of action, and the potential benefits of natural
      compounds with antagonistic effects on GPCRs, especially those containing CCR2,
      for neuropathic pain treatment.

PMID- 27891522
TI  - Biomolecular Network-Based Synergistic Drug Combination Discovery.
AB  - Drug combination is a powerful and promising approach for complex disease therapy
      such as cancer and cardiovascular disease. However, the number of synergistic
      drug combinations approved by the Food and Drug Administration is very small. To
      bridge the gap between urgent need and low yield, researchers have constructed
      various models to identify synergistic drug combinations. Among these models,
      biomolecular network-based model is outstanding because of its ability to reflect
      and illustrate the relationships among drugs, disease-related genes, therapeutic
      targets, and disease-specific signaling pathways as a system. In this review, we
      analyzed and classified models for synergistic drug combination prediction in
      recent decade according to their respective algorithms. Besides, we collected
      useful resources including databases and analysis tools for synergistic drug
      combination prediction. It should provide a quick resource for computational
      biologists who work with network medicine or synergistic drug combination
      designing.

PMID- 27891523
TI  - 5HT3 Antagonists versus Dexamethasone in the Prevention of PONV in Patients
      Undergoing Laparoscopic Cholecystectomy: A Meta-Analysis of RCTs.
AB  - Background. 5HT3 antagonist, an antiemetic alternative to dexamethasone, is an
      effective drug for the prevention of postoperative nausea and vomiting (PONV).
      Methods. PubMed and The Cochrane Library (from inception to June 2016) were
      searched for relevant RCTs (randomized controlled trials). Results. Seven trials,
      totaling 682 patients, were included in this meta-analysis. This meta-analysis
      demonstrated that 5HT3 antagonist was as effective as dexamethasone in preventing
      PONV (RR, 1.12; 95% CI, [0.86, 1.45]; P = 0.40) within 24 hours of laparoscopic
      cholecystectomy, and no significant heterogeneity was observed among the studies
      (I2 = 0%; P = 0.98). During the early postoperative period (0-6 h), 5HT3
      antagonists were superior to dexamethasone in reducing POV (RR, 0.31; 95% CI,
      [0.11, 0.93]; P = 0.04), while, in other postoperative stages (6-12 h, 12-24 h,
      and 0-24 h), it was not more effective in the prevention of POV than
      dexamethasone. And no significant difference was found in the prevention of PON
      between 5HT3 antagonists and dexamethasone at different postoperative periods (0
      6 h, 6-12 h, 12-24 h, and 0-24 h). Conclusions. As a result, it is advisable to
      encourage 5HT3 antagonists as an alternative to dexamethasone for the prevention
      of PONV in patients undergoing laparoscopic cholecystectomy.

PMID- 27891524
TI  - The Design, Usability, and Feasibility of a Family-Focused Diabetes Self-Care
      Support mHealth Intervention for Diverse, Low-Income Adults with Type 2 Diabetes.
AB  - Family members' helpful and harmful actions affect adherence to self-care and
      glycemic control among adults with type 2 diabetes (T2D) and low socioeconomic
      status. Few family interventions for adults with T2D address harmful actions or
      use text messages to reach family members. Through user-centered design and
      iterative usability/feasibility testing, we developed a mHealth intervention for
      disadvantaged adults with T2D called FAMS. FAMS delivers phone coaching to set
      self-care goals and improve patient participant's (PP) ability to identify and
      address family actions that support/impede self-care. PPs receive text message
      support and can choose to invite a support person (SP) to receive text messages.
      We recruited 19 adults with T2D from three Federally Qualified Health Centers to
      use FAMS for two weeks and complete a feedback interview. Coach-reported data
      captured coaching success, technical data captured user engagement, and PP/SP
      interviews captured the FAMS experience. PPs were predominantly African American,
      83% had incomes <$35,000, and 26% were married. Most SPs (n = 7) were
      spouses/partners or adult children. PPs reported FAMS increased self-care and
      both PPs and SPs reported FAMS improved support for and communication about
      diabetes. FAMS is usable and feasible and appears to help patients manage self
      care support, although some PPs may not have a SP.

PMID- 27891525
TI  - A Validation Study of Administrative Claims Data to Measure Ovarian Cancer
      Recurrence and Secondary Debulking Surgery.
AB  - OBJECTIVE: Administrative claims data offer an alternative to chart abstraction
      to assess ovarian cancer recurrence, treatment and outcomes. Such analyses have
      been hindered by lack of valid recurrence and treatment algorithms. In this
      study, we sought to develop claims-based algorithms to identify ovarian cancer
      recurrence and secondary debulking surgery, and to validate them against the gold
      standard of chart abstraction. METHODS: We conducted chart validation studies; 2
      recurrence algorithms and 1 secondary surgery among 94 ovarian cancer patients
      treated at one hospital between 2003-2009. A new recurrence algorithm was based
      on treatment timing (>=6 months after primary treatment) and a previously
      validated algorithm was based on secondary malignancy codes. A secondary
      debulking surgery algorithm was based on surgical billing codes. RESULTS: The new
      recurrence algorithm had: sensitivity=100% (95% confidence interval [CI]=87%
      =100%), specificity=89% (95%CI=78%-95%), kappa=84% (SE=10%) while the secondary
      malignancy-=code recurrence algorithm had: sensitivity=84% (95%CI=66%-94%),
      specificity=44% (95%CI=31%-=57%), kappa=23% (SE=8%). The secondary surgery
      algorithm had: sensitivity=77% (95%CI=50%-92%), = specificity= 92% (95%CI=83%
      97%), kappa=66% (SE=10%).=. CONCLUSIONS: A recurrence algorithm based on
      treatment timing accurately identified ovarian cancer =recurrence. If validated
      in other populations, such an algorithm can provide a tool to compare
      effectiveness of recurrent ovarian cancer treatments.

PMID- 27891526
TI  - Comparative Effectiveness Research Using Observational Data: Active Comparators
      to Emulate Target Trials with Inactive Comparators.
AB  - INTRODUCTION: Because a comparison of noninitiators and initiators of treatment
      may be hopelessly confounded, guidelines for the conduct of observational
      research often recommend using an "active" comparator group consisting of people
      who initiate a treatment other than the medication of interest. In this paper, we
      discuss the conditions under which this approach is valid if the goal is to
      emulate a trial with an inactive comparator. IDENTIFICATION OF EFFECTS: We
      provide conditions under which a target trial in a subpopulation can be validly
      emulated from observational data, using an active comparator that is known or
      believed to be inactive for the outcome of interest. The average treatment effect
      in the population as a whole is not identified, but under certain conditions this
      approach can be used to emulate a trial in the subset of individuals who were
      treated with the treatment of interest, in the subset of individuals who were
      treated with the treatment of interest but not with the comparator, or in the
      subset of individuals who were treated with both the treatment of interest and
      the active comparator. THE PLAUSIBILITY OF THE COMPARABILITY CONDITIONS: We
      discuss whether the required conditions can be expected to hold in
      pharmacoepidemiologic research, with a particular focus on whether the conditions
      are plausible in situations where the standard analysis fails due to unmeasured
      confounding by access to health care or health seeking behaviors. DISCUSSION: The
      conditions discussed in this paper may at best be approximately true.
      Investigators using active comparator designs to emulate trials with inactive
      comparators should exercise caution.

PMID- 27891527
TI  - The Multimorbidity Index: A Tool for Assessing the Prognosis of Patients from
      Their History of Illness.
AB  - BACKGROUND: The Multimorbidity (MM) Index predicts the prognosis of patients from
      their diagnostic history. In contrast to existing approaches with broad
      diagnostic categories, it treats each diagnosis as a separate independent
      variable using individual International Classification of Disease, Revision 9
      (ICD-9) codes. OBJECTIVE: This paper describes the MM Index, reviews the
      published data on its accuracy, and provides procedures for implementing the
      Index within electronic health record (EHR) systems. Methods: The MM Index was
      tested on various patient populations by using data from the United States
      Department of Veterans Affairs data warehouse and claims data within the
      Healthcare Cost and Utilization Project of the Agency for Health Care Research
      and Quality. RESULTS: In cross-validated studies, the MM Index outperformed
      prognostic indices based on physiological markers, such as CD4 cell counts in
      HIV/AIDS, HbAlc levels in diabetes, ejection fractions in heart failure, or the
      13 physiological markers commonly used for patients in intensive care units. When
      predicting the prognosis of nursing home patients by using the cross-validated
      area under a receiver operating characteristic (ROC) curve, the MM Index was 15
      percent outperformed the Quan variant of the Charlson Index, 27 percent more
      accurate than the Deyo variant of the Charlson Index, and 22 percent more
      accurate than the von Walraven variant of the Elixhauser Index. For patients in
      intensive care units, the MM Index was 13 percent outperformed the cross
      validated area under ROC associated with Elixhauser's categories. The MM Index
      also demonstrated greater accuracy than a number of commercially available
      measures of illness severity; including a fivefold greater accuracy than the All
      Patient Refined Diagnosis-Related Groups and a threefold greater accuracy than
      All Payer Severity-Adjusted Diagnosis-Related Groups. CONCLUSION: The MM Index is
      statistically more accurate than many existing measures of prognosis. The
      magnitude of improvement is large and may lead to a clinically meaningful
      difference in patient care. Given the large improvements in accuracy, the use of
      the MM Index for policy and comparative effectiveness analysis is recommended.

PMID- 27891528
TI  - Preparing Nursing Home Data from Multiple Sites for Clinical Research - A Case
      Study Using Observational Health Data Sciences and Informatics.
AB  - INTRODUCTION: A potential barrier to nursing home research is the limited
      availability of research quality data in electronic form. We describe a case
      study of converting electronic health data from five skilled nursing facilities
      to a research quality longitudinal dataset by means of open-source tools produced
      by the Observational Health Data Sciences and Informatics (OHDSI) collaborative.
      METHODS: The Long-Term Care Minimum Data Set (MDS), drug dispensing, and fall
      incident data from five SNFs were extracted, translated, and loaded into version
      4 of the OHDSI common data model. Quality assurance involved identifying errors
      using the Achilles data characterization tool and comparing both quality measures
      and drug exposures in the new database for concordance with externally available
      sources. FINDINGS: Records for a total 4,519 patients (95.1%) made it into the
      final database. Achilles identified 10 different types of errors that were
      addressed in the final dataset. Drug exposures based on dispensing were generally
      accurate when compared with medication administration data from the pharmacy
      services provider. Quality measures were generally concordant between the new
      database and Nursing Home Compare for measures with a prevalence >= 10%. Fall
      data recorded in MDS was found to be more complete than data from fall incident
      reports. CONCLUSIONS: The new dataset is ready to support observational research
      on topics of clinical importance in the nursing home including patient-level
      prediction of falls. The extraction, translation, and loading process enabled the
      use of OHDSI data characterization tools that improved the quality of the final
      dataset.

PMID- 27891530
TI  - Independent Spanish Validation of the Unified Dyskinesia Rating Scale.
AB  - The Unified Dyskinesia Rating Scale (UDysRS) assesses the severity and disability
      caused by dyskinesias in Parkinson's disease (PD). As part of the UDysRS
      development plan, the International Parkinson and Movement Disorder Society (MDS)
      established guidelines for official non-English translations. We present here the
      formal process for completing this program and the data on the first officially
      approved non-English version of the UDysRS (Spanish). The UDysRS translation
      program involves four steps: translation and back-translation; cognitive
      pretesting to ensure that raters and patients understand the scale and are
      comfortable with its content; field testing of the finalized version; and
      analysis of the factor structure of the tested version against the original
      English-language version. To be designated an official MDS translation, the
      confirmatory factor analysis comparative fit index (CFI) had to be >=0.90. The
      Spanish UDysRS was tested in 253 native-Spanish-speaking patients with PD. For
      all four parts of the UDysRS, the CFI, was >=0.94. Exploratory factor analyses of
      the Spanish version revealed a very clear factor structure, with three factors
      related to ON dyskinesia, OFF dystonia, and patient perceptions of the functional
      effect of dyskinesias. The Spanish version of the UDysRS successfully followed
      the MDS Translation Program protocol, reached the criterion to be designated as
      an official translation, and is now available on the MDS website for use.

PMID- 27891531
TI  - Origanum majorana Essential Oil Lacks Mutagenic Activity in the
      Salmonella/Microsome and Micronucleus Assays.
AB  - The present study aimed to investigate the in vitro mutagenic activity of
      Origanum majorana essential oil. The most abundant compounds identified by GC-MS
      were gamma-terpinene (25.73%), alpha-terpinene (17.35%), terpinen-4-ol (17.24%),
      and sabinene (10.8%). Mutagenicity was evaluated by the Salmonella/microsome test
      using the preincubation procedure on TA98, TA97a, TA100, TA102, and TA1535
      Salmonella typhimurium strains, in the absence or in the presence of metabolic
      activation. Cytotoxicity was detected at concentrations higher than 0.04
      MUL/plate in the absence of S9 mix and higher than 0.08 MUL/plate in the presence
      of S9 mix and no gene mutation increase was observed. For the in vitro mammalian
      cell micronucleus test, V79 Chinese hamster lung fibroblasts were used.
      Cytotoxicity was only observed at concentrations higher than or equal to 0.05
      MUg/mL. Moreover, when tested in noncytotoxic concentrations, O. majorana
      essential oil was not able to induce chromosome mutation. The results from this
      study therefore suggest that O. majorana essential oil is not mutagenic at the
      concentrations tested in the Salmonella/microsome and micronucleus assays.

PMID- 27891529
TI  - Novel Approaches to the Prevention and Treatment of Rabies.
AB  - Rabies is a highly lethal disease caused by the neurotropic rabies virus (RABV),
      and it remains an important public health problem globally. Effective vaccines
      have been developed for pre- and post-exposure prophylaxis (PEP). PEP is only
      effective if it is initiated promptly after recognizing exposure. Once
      neurological symptoms develop, however, it is widely accepted that there is no
      effective treatment available. Recent studies indicate that the presence of RABV
      specific immunity (i.e. Virus neutralizing antibodies, VNA) and the transient
      enhancement of the BBB permeability are absolutely required for effective virus
      clearance from the CNS. In principle, it has been shown in mice using various
      live-attenuated RABVs or recombinant RABVs expressing three copies of the G or
      expressing chemokine/cytokines, which can induce high levels of VNA in the serum
      and also capable of transiently enhancing the BBB permeability that it is
      possible to clear the virus from CNS. Also, it has been demonstrated that,
      intravenous administration of VNA together with MCP-1 (shown to transiently open
      up BBB) can clear RABV from the CNS in both immunocompetent and immunocompromised
      mice, as late as 5 days after lethal challenge. Novel therapeutic approaches
      aimed at allowing the peripheral VNA to cross the BBB by administration of the
      VNA in combination with biological or chemical agents that can transiently open
      up the BBB would be useful to establish an effective therapy for rabies in
      humans. In this review, we focus on the some of the approaches that can be used
      to meet the challenges in the field of rabies treatment.

PMID- 27891532
TI  - Health Center Professional Programs and Primary Care Workforce.
AB  - BACKGROUND: Current policy promotes health center professional training and
      pipeline programs as solutions to bolster primary care workforce in shortage
      areas, despite the paucity of evidence. METHODS: We analyzed data from US health
      centers we surveyed from March to June 2010, merged with federal health center
      data, to estimate associations between health center training and pipeline
      programs and provider recruitment and retention. RESULTS: Of the 976 surveyed,
      391 health centers responded. Health centers with career ladder programs compared
      to those without had higher adjusted rates of no/minimal difficulty in
      recruitment of primary care providers. (17.6% vs. 10.6%; p=.01) and close to
      double the adjusted rates of reporting no/minimal difficulty in retention of
      primary care providers (39.4% vs. 21.2%; p=.0001). DISCUSSION: There remains a
      need for further evaluation of health professional programs in order to expand
      models, such as career ladder programs, that demonstrate effectiveness in
      improving the primary care workforce in shortage areas.

PMID- 27891533
TI  - Screening for Cancer in Persons Living with HIV Infection.
AB  - Survival with human immunodeficiency virus (HIV) infection has greatly improved
      due to effective antiretroviral therapy (ART). As infectious complications have
      declined, malignancy now accounts for over one-third of deaths among people
      living with HIV (PLWH). Based on practices in the general population, cancer
      screening of PLWH can decrease both morbidity and mortality. In this article, we
      review and consider directed approaches for colorectal, breast, cervical and lung
      cancer screening. Furthermore, routine physical examinations may detect lymphomas
      and skin, anal and oral cancers. Comprehensive cancer prevention in PLWH should
      also include ART adherence, vaccination against oncogenic viruses, treatment of
      hepatitis viruses and smoking cessation. Cancer screening for PLWH warrants
      further research on safety and efficacy as well as targeted efforts to increase
      adherence.

PMID- 27891534
TI  - Graphene Oxide Nanosheets Stimulate Ruffling and Shedding of Mammalian Cell
      Plasma Membranes.
AB  - Graphene oxide (GO) has attracted intense interest for use in living systems and
      environmental applications. GO's compatibility with mammalian cells is sometimes
      inferred from its low cytotoxicity, but such conclusions ignore non-lethal
      effects that will influence GO's utility. Here we demonstrate, with rat
      basophilic leukemia (RBL) cells, profound plasma membrane (PM) ruffling and
      shedding induced by GO using confocal and live cell fluorescence microscopy, as
      well as scanning electron microscopy. These membrane structures contain
      immunoglobulin E receptors, are resistant to detergents, and lack detectable
      fluorescence labeling of F-actin and fibronectin. The formation of these membrane
      structures correlates with a loss of contact inhibition between RBL cells. We
      observe similar cellular responses towards GO for NIH-3T3 fibroblast cells and
      MDA-MB-231 human breast cancer cells. These findings reveal a previously
      unreported cellular response towards foreign nanomaterials. Membrane ruffling and
      shedding raise fundamental questions about how GO interacts with the PM, as well
      as its potential to modulate cellular mechanosensing for tissue engineering, stem
      cell differentiation, and other biomedical applications.

PMID- 27891536
TI  - Use of organolanthanides in the catalytic intermolecular hydrophosphination and
      hydroamination of multiple C-C bonds.
AB  - This review covers recent achievements in the intermolecular hydrophosphination
      and hydroamination of alkenes, dienes and alkynes catalyzed by organolanthanides.

PMID- 27891535
TI  - Gene therapy for hemoglobin disorders - a mini-review.
AB  - Gene therapy by either gene insertion or editing is an exciting curative
      therapeutic option for monogenic hemoglobin disorders like sickle cell disease
      and beta-thalassemia. The safety and efficacy of gene transfer techniques has
      markedly improved with the use of lentivirus vectors. The clinical translation of
      this technology has met with good success, although key limitations include
      number of engraftable transduced hematopoietic stem cells and adequate transgene
      expression that results in complete correction of beta0 thalassemia major. This
      highlights the need to identify and address factors that might be contributing to
      the in-vivo survival of the transduced hematopoietic stem cells or find means to
      improve expression from current vectors. In this review, we briefly discuss the
      gene therapy strategies specific to hemoglobinopathies, the success of the
      preclinical models and the current status of gene therapy clinical trials.

PMID- 27891537
TI  - On-demand magnetic manipulation of liquid metal in microfluidic channels for
      electrical switching applications.
AB  - We report magnetic-field-driven on-demand manipulation of liquid metal in
      microfluidic channels filled with base or acid. The liquid metal was coated with
      iron (Fe) particles and treated with hydrochloric acid to have strong bonding
      strength with the Fe particles. The magnetic liquid metal slug inserted in the
      microchannel is manipulated, merged, and separated. In addition, corresponding to
      the repositioning of an external magnet, the liquid metal slug can be readily
      moved in microfluidic channels with different angles (>90 degrees ) and cross
      linked channels in any direction. We demonstrated the functionality of the liquid
      metal in the microfluidic channel for electrical switching applications by
      manipulation of the liquid metal, resulting in the sequential turning on of light
      emitting diodes (LEDs).

PMID- 27891538
TI  - Slip of polymer melts over micro/nano-patterned metallic surfaces.
AB  - The slip behavior of high-density polyethylenes (HDPEs) is studied over surfaces
      of different topology and surface energy. Laser ablation has been used to
      micro/nano-pattern the surface of dies in order to examine the effect of surface
      roughness on slip. In addition, fluoroalkyl silane-based coatings on smooth and
      patterned substrates were used to understand the effect of surface energy on
      slip. Surface roughness and surface energy effects were incorporated into the
      double reptation slip model (Ebrahimi et al., J. Rheol., 2015, 59, 885-901) in
      order to predict the slip velocity of studied polymers on different substrates.
      It was found that for dies with rough surfaces, polymer melt penetrates into the
      cavities of the substrate (depending on the depth and the distance between the
      asperities), thus decreasing wall slip. On the other hand, silanization of the
      surface increases the slip velocity of polymers in the case of smooth die,
      although it has a negligible effect on rough dies. Interestingly, the slip
      velocity of the studied polymers on various substrates of different degrees of
      roughness and surface energy, were brought into a mastercurve by modifying the
      double reptation slip velocity model.

PMID- 27891539
TI  - Pincer-plus-one ligands in self-assembly with palladium(ii): a molecular square
      and a molecular tetrahedron.
AB  - The combination of a palladium(ii) precursor with a diimine-phenol ligand and an
      oxidant (H2O2 or O2) under different conditions has, serendipitously, given both
      a molecular square and a molecular tetrahedron by self-assembly of building
      blocks comprising palladium(ii) centres coordinated to the oxidised forms of the
      ligand.

PMID- 27891541
TI  - DFT calculations in the assignment of solid-state NMR and crystal structure
      elucidation of a lanthanum(iii) complex with dithiocarbamate and phenanthroline.
AB  - The molecular, crystal, and electronic structures as well as spectroscopic
      properties of a mononuclear heteroleptic lanthanum(iii) complex with
      diethyldithiocarbamate and 1,10-phenanthroline ligands (3 : 1) were studied by
      solid-state 13C and 15N cross-polarisation (CP) magic-angle-spinning (MAS) NMR, X
      ray diffraction (XRD), and first principles density functional theory (DFT)
      calculations. A substantially different powder XRD pattern and 13C and 15N CP-MAS
      NMR spectra indicated that the title compound is not isostructural to the
      previously reported analogous rare earth complexes with the space group P21/n.
      Both 13C and 15N CP-MAS NMR revealed the presence of six structurally different
      dithiocarbamate groups in the asymmetric unit cell, implying a non
      centrosymmetric packing arrangement of molecules. This was supported by single
      crystal X-ray crystallography showing that the title compound crystallised in the
      triclinic space group P1[combining macron]. In addition, the crystal structure
      also revealed that one of the dithiocarbamate ligands has a conformational
      disorder. NMR chemical shift calculations employing the periodic gauge including
      projector augmented wave (GIPAW) approach supported the assignment of the
      experimental 13C and 15N NMR spectra. However, the best correspondences were
      obtained with the structure where the atomic positions in the X-ray unit cell
      were optimised at the DFT level. The roles of the scalar and spin-orbit
      relativistic effects on NMR shielding were investigated using the zeroth-order
      regular approximation (ZORA) method with the outcome that already the scalar
      relativistic level qualitatively reproduces the experimental chemical shifts. The
      electronic properties of the complex were evaluated based on the results of the
      natural bond orbital (NBO) and topology of the electron density analyses.
      Overall, we apply a multidisciplinary approach acquiring comprehensive
      information about the solid-state structure and the metal-ligand bonding of the
      heteroleptic lanthanum complex.

PMID- 27891542
TI  - [Ti12In6O18(OOCC6H5)30]: a multifunctional hetero-polyoxotitanate nanocluster
      with high stability and visible photoactivity.
AB  - We present a novel strategy to improve the stability and optical absorption of
      polyoxotitanates (POTs) via concurrently fully carboxylate-coordinating and
      hetero-metal-doping, and illustrate the strategy by an indium doped hetero
      polyoxotitanate (h-POT) of a [Ti12In6O18(OOCC6H5)30] (POTi12In6) nanocluster,
      which possesses ultrahigh stability in both acid and base aqueous solutions. The
      nanocluster structurally features a core-shell double wheel structure and a polar
      cavity. Both experiments and theoretical calculations confirm the semiconductive
      properties of the nanocluster. Under visible irradiation the POTi12In6
      nanocluster can produce pronounced photocurrent, and reactive oxygen species for
      pollutant degradation. Without using any cocatalyst, POTi12In6 exhibits important
      visible-light-driven photocatalytic activity for H2 evolution in an aqueous
      system. This work could render a polyoxotitanate as a new type of visible
      photoactive photocatalyst.

PMID- 27891543
TI  - Dynamic neighbouring participation of nitrogen lone pairs on the chromogenic
      behaviour of trans-bis(salicylaldiminato)Pt(ii) coordination platforms.
AB  - The participation of neighbouring nitrogen lone pairs in the chromogenic control
      of trans-bis(salicylaldiminato)Pt(ii) platforms was examined, using newly
      designed Pt analogues bearing salicylaldehyde hydrazone ligands. A series of non
      vaulted and vaulted Pt complexes (1-5) with salicylaldehyde hydrazones as trans
      coordinated bidentate ligands were synthesized and characterized with regard to
      the chromogenic behaviour of the trans-bis(salicylaldiminato)Pt(ii) coordination
      platforms. X-ray diffraction and 2D NMR data demonstrated that, in the case of
      the non-vaulted N-monomethyl complexes 1, there was significant participation of
      neighbouring N(2) lone pairs in the d-pi conjugation of the trans
      bis(salicylaldiminato)Pt(ii) platforms owing to conformational fixation arising
      from intramolecular hydrogen bonding. In contrast, the lone pairs of the N,N
      dimethyl analogues 2 made a much less significant contribution to the extension
      of the d-pi conjugation, due to their high conformational mobility. Complexes 1-5
      were found to have structure-dependent chromogenic properties in the solution
      state, such that the absorption spectra of the N-methyl, short-vaulted complexes
      1 and 3 exhibited significant hypsochromic shifts relative to the N,N-dimethyl,
      long-vaulted analogues 2 and 5, which had spectra very similar to that of the
      trans-bis(salicylaldiminato)Pt(ii) complex 6. The introduction of MeO groups at
      the 3- and 5 positions on the aromatic rings of 1 and 2 gave rise to significant
      hypsochromic and bathochromic shifts, respectively. In addition, numax - ET(30)
      plots for various solvents revealed that complexes 1-5 exhibit negative
      solvatochromism, in which the data obtained in alcoholic solvents are
      hypsochromically separated from those in non-alcoholic solvents for 1 and 3, an
      effect that is not observed for 2 and 5. Complexes 1-5 also exhibit emission
      enhancement upon addition of excess CH3SO3H in dimethyl sulfoxide, and a
      significant effect of the linker on quantum yields (Phi77 K) was observed in the
      case of the vaulted complexes. Density functional theory calculations (B3LYP/6
      31G*, LanL2DZ) determined that the structure dependence of the chromogenic
      behaviour of these non-vaulted and polymethylene-vaulted hydrazone complexes can
      be attributed to variations in the participation of neighbouring nitrogen lone
      pairs in the d-pi conjugation on the trans-bis(salicylaldiminato)Pt(ii)
      coordination platforms.

PMID- 27891544
TI  - An in vitro digestion method adapted for carotenoids and carotenoid esters:
      moving forward towards standardization.
AB  - In vitro digestion methods are a useful approach to predict the bioaccessibility
      of food components and overcome some limitations or disadvantages associated with
      in vivo methodologies. Recently, the INFOGEST network published a static method
      of in vitro digestion with a proposal for assay standardization. The INFOGEST
      method is not specific for any food component; therefore, we aimed to adapt this
      method to assess the in vitro bioaccessibility of carotenoids and carotenoid
      esters in a model fruit (Byrsonima crassifolia). Two additional steps were
      coupled to the in vitro digestion procedure, centrifugation at 20 000g for the
      separation of the aqueous phase containing mixed micelles and exhaustive
      carotenoid extraction with an organic solvent. The effect of electrolytes,
      enzymes and bile acids on carotenoid micellarization and stability was also
      tested. The results were compared with those found with a simpler method that has
      already been used for carotenoid bioaccessibility analysis. These values were in
      the expected range for free carotenoids (5-29%), monoesters (9-26%) and diesters
      (4-28%). In general, the in vitro bioaccessibility of carotenoids assessed by the
      adapted INFOGEST method was significantly higher (p < 0.05) than those assessed
      by the simplest protocol, with or without the addition of simulated fluids.
      Although no trend was observed, differences in bioaccessibility values depended
      on the carotenoid form (free, monoester or diester), isomerization (Z/E) and the
      in vitro digestion protocol. To the best of our knowledge, it was the first time
      that a systematic identification of carotenoid esters by HPLC-DAD-MS/MS after in
      vitro digestion using the INFOGEST protocol was carried out.

PMID- 27891540
TI  - Advancement of mass spectrometry-based proteomics technologies to explore triple
      negative breast cancer.
AB  - Understanding the complexity of cancer biology requires extensive information
      about the cancer proteome over the course of the disease. The recent advances in
      mass spectrometry-based proteomics technologies have led to the accumulation of
      an incredible amount of such proteomic information. This information allows us to
      identify protein signatures or protein biomarkers, which can be used to improve
      cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based
      proteomics has been used in breast cancer research for over two decades to
      elucidate protein function. Breast cancer is a heterogeneous group of diseases
      with distinct molecular features that are reflected in tumour characteristics and
      clinical outcomes. Compared with all other subtypes of breast cancer, triple
      negative breast cancer is perhaps the most distinct in nature and heterogeneity.
      In this review, we provide an introductory overview of the application of
      advanced proteomic technologies to triple-negative breast cancer research.

PMID- 27891545
TI  - Phosphine-imine and -enamido ligands for acceptorless dehydrogenation catalysis.
AB  - A highly tunable phosphine-imine ligand family is introduced. Following
      metallation with ruthenium, deprotonation of the ligand affords a phosphine
      enamido species. Complexes with the ligand in both the imine and enamido forms
      are active toward acceptorless dehydrogenation reactions.

PMID- 27891546
TI  - CT image quality in sinogram affirmed iterative reconstruction phantom study - is
      there a point of diminishing returns?
AB  - BACKGROUND: In our pediatric practice, we have observed qualitatively limited
      improvement in the image quality of images generated with sinogram affirmed
      iterative reconstruction (SAFIRE) compared to series generated with filtered back
      projection (FBP), particularly in cases near or below a CT dose index volume
      (CTDIvol) of 1-mGy. OBJECTIVE: To determine whether the image quality advantage
      of SAFIRE remains constant across clinically used CT dose levels in an American
      College of Radiology (ACR) CT accreditation phantom including the lower dose
      range used in pediatric imaging. MATERIALS AND METHODS: An exemption from
      institutional review board approval was obtained for this phantom-based study. An
      ACR quality phantom was scanned in incremental kV steps and effective tube
      current intervals. Acquisitions were reconstructed with FBP and SAFIRE strengths
      of 1, 3 and 5. Image quality measures were calculated including signal-to-noise
      ratio (SNR), contrast-to-noise ratio (CNR), low-contrast resolution and high
      contrast resolution. Peak SNR was also calculated. Descriptive and nonparametric
      statistics were used to compare these image quality metrics while normalizing to
      CT dose index (CTDI). RESULTS: The percent improvement in SNR and peak SNR of
      SAFIRE reconstructions compared to FBP decreased from about 70% for image sets
      acquired above a 1.42 mGy CTDI to 25% at a 0.25 mGy CTDI. CNR improvement with
      SAFIRE did not vary with dose. No significant difference was seen in the low
      contrast resolution or high-contrast resolution of SAFIRE images compared to FBP.
      CONCLUSION: SNR did not improve equally after applying SAFIRE across a spectrum
      clinically used CTDIs. Below a threshold CTDI, the incremental improvement of
      SAFIRE compared to FBP decreased.

PMID- 27891548
TI  - Falciform ligament sign.

PMID- 27891547
TI  - Severe pelvic injury: vascular lesions detected by ante- and post-mortem contrast
      medium-enhanced CT and associations with pelvic fractures.
AB  - OBJECTIVES: The objectives of this study were to compare arterial and venous
      contrast medium extravasation in severe pelvic injury detected by ante- and post
      mortem multi-detector CT (MDCT) and determine whether vascular injury is
      associated with certain types of pelvic fracture. METHODS: We retrospectively
      included two different cohorts of blunt pelvic trauma with contrast medium
      extravasation shown by MDCT. The first group comprised 49 polytrauma patients;
      the second included 45 dead bodies undergoing multi-phase post-mortem CT
      angiography (MPMCTA). Two radiologists jointly reviewed each examination
      concerning type, site of bleeding and pattern of underlying pelvic ring fracture.
      RESULTS: All 49 polytrauma patients demonstrated arterial bleeding, immediately
      undergoing subsequent angiography; 42 (85%) had pelvic fractures, but no venous
      bleeding was disclosed. MPMCTA of 45 bodies revealed arterial (n = 33, 73%) and
      venous (n = 35, 78%) bleeding and pelvic fractures (n = 41, 91%). Pelvic fracture
      locations were significantly correlated with ten arterial and six venous bleeding
      sites in dead bodies, with five arterial bleeding sites in polytrauma patients.
      In dead bodies, arterial haemorrhage was significantly correlated with the
      severity of pelvic fracture according to Tile classification (p = 0.01), unlike
      venous bleeding (p = 0.34). CONCLUSIONS: In severe pelvic injury, certain acute
      bleeding sites were significantly correlated with underlying pelvic fracture
      locations. MPMCTA revealed more venous lesions than MDCT in polytrauma patients.
      Future investigations should evaluate the proportional contribution of venous
      bleeding to overall pelvic haemorrhage as well as its clinical significance.

PMID- 27891549
TI  - A pilot study of the diagnostic and prognostic values of FLT-PET/CT for
      pancreatic cancer: comparison with FDG-PET/CT.
AB  - PURPOSE: The purpose of the study was to examine the diagnostic and prognostic
      values of 18F-fluorothymidine (FLT)-PET/CT for pancreatic cancer by comparing
      with 18F-fluorodeoxyglucose (FDG)-PET/CT. METHODS: Fifteen patients with newly
      diagnosed pancreatic cancer underwent both FLT and FDG-PET/CT scans before
      treatment. The sensitivity, specificity, and accuracy in detecting nodal and
      distant metastases were compared between both scans using McNemar exact or chi 2
      test. Progression-free survival (PFS) and overall survival (OS) were calculated
      by Kaplan-Meier method. Prognostic significance was assessed by Cox proportional
      hazards analysis. RESULTS: Both scans visualized all primary cancers. The
      sensitivity, specificity, and accuracy per patient basis for detecting nodal
      metastasis were equal and 63.6% (7/11), 100% (4/4), and 73.3% (11/15) for both
      scans, and for detecting distant metastasis were 100% (6/6), 88.9% (8/9), and
      93.3% (14/15) for FDG-PET/CT, and 50.0% (3/6), 100% (9/9), and 80.0% (12/15) for
      FLT-PET/CT, respectively, without significant difference in each of them between
      both scans (p > 0.05). However, of 4 patients with multiple liver metastases, FDG
      PET/CT was positive in all, but FLT-PET/CT was negative in three patients. At
      univariate analysis, only FLT-SUVmax correlated with PFS (hazard ratio, 1.306, p
      = 0.048), and FDG total lesion glycolysis (TLG), FLT-SUVmax, and FLT-total lesion
      proliferation (TLP) correlated with OS (p = 0.021, p = 0.005, and p = 0.022,
      respectively). At bivariate analysis, FLT-SUVmax was superior to FDG-TLG or FLT
      TLP for prediction of OS [HR (adjusted for FDG-TLG), 1.491, p = 0.034, HR
      (adjusted for FLT-TLP), 1.542, p = 0.023]. CONCLUSION: FLT-PET/CT may have a
      potential equivalent to FDG-PET/CT for detecting primary and metastatic cancers
      except liver metastasis. FLT-SUVmax can provide the most significant prognostic
      information.

PMID- 27891550
TI  - Improved diagnosis of common bile duct stone with single-shot balanced turbo
      field-echo sequence in MRCP.
AB  - PURPOSE: To evaluate the value of adding single-shot balanced turbo field-echo (b
      TFE) sequence to conventional magnetic resonance cholangiopancreatography (MRCP)
      for the detection of common bile duct (CBD) stone. METHODS: One hundred thirty
      seven consecutive patients with suspected CBD stone underwent MRCP including
      single-shot b-TFE sequence. Twenty-five patients were confirmed with CBD stone by
      endoscopic retrograde cholangiopancreatography or ultrasonography. Two
      radiologists reviewed two image protocols: protocol A (conventional MRCP
      protocol: unenhanced T1-, T2-, and respiratory-triggered three-dimensional fat
      suppressed single-shot turbo spin-echo MRCP sequence) and protocol B (protocol A
      plus single-shot b-TFE sequence). The sensitivity, specificity, positive (PPV)
      and negative predictive value (NPV), and area under the receiver-operating
      characteristic (ROC) curve (AUC) for the detection of CBD stone were compared.
      RESULTS: The sensitivity (72%) and NPV (94%) were the same between the two
      protocols. However, protocol B was greater in the specificity (99%) and PPV (94%)
      than protocol A (92% and 67%, respectively) (P = 0.0078 and 0.031, respectively).
      The AUC was significantly greater for protocol B (0.93) than for protocol A
      (0.86) (P = 0.026). CONCLUSIONS: Inclusion of single-shot b-TFE sequence to
      conventional MRCP significantly improved the specificity and PPV for the
      detection of CBD stone.

PMID- 27891551
TI  - Colorectal cancer staging: comparison of whole-body PET/CT and PET/MR.
AB  - PURPOSE: Correct staging is imperative for colorectal cancer (CRC) since it
      influences both prognosis and management. Several imaging methods are used for
      this purpose, with variable performance. Positron emission tomography-magnetic
      resonance (PET/MR) is an innovative imaging technique recently employed for
      clinical application. The present study was undertaken to compare the staging
      accuracy of whole-body positron emission tomography-computed tomography (PET/CT)
      with whole-body PET/MR in patients with both newly diagnosed and treated
      colorectal cancer. METHODS: Twenty-six patients, who underwent same day whole
      body (WB) PET/CT and WB-PET/MR, were evaluated. PET/CT and PET/MR studies were
      interpreted by consensus by a radiologist and a nuclear medicine physician.
      Correlations with prior imaging and follow-up studies were used as the reference
      standard. Correct staging was compared between methods using McNemar's Chi square
      test. RESULTS: The two methods were in agreement and correct for 18/26 (69%)
      patients, and in agreement and incorrect for one patient (3.8%). PET/MR and
      PET/CT stages for the remaining 7/26 patients (27%) were discordant, with PET/MR
      staging being correct in all seven cases. PET/MR significantly outperformed
      PET/CT overall for accurate staging (P = 0.02). CONCLUSION: PET/MR outperformed
      PET/CT in CRC staging. PET/MR might allow accurate local and distant staging of
      CRC patients during both at the time of diagnosis and during follow-up.

PMID- 27891553
TI  - Core curriculum illustration: dural venous sinus thrombosis.
AB  - This is the 25th installment of a series that will highlight one case per
      publication issue from the bank of cases available online as a part of the
      American Society of Emergency Radiology (ASER) educational resources. Our goal is
      to generate more interest in and use of our online materials. To view more cases
      online, please visit the ASER Core Curriculum and Recommendations for study
      online at http://www.aseronline.org/curriculum/toc.htm .

PMID- 27891554
TI  - Teaching Genetic Counseling Skills: Incorporating a Genetic Counseling Adaptation
      Continuum Model to Address Psychosocial Complexity.
AB  - Genetic counselors are trained health care professionals who effectively
      integrate both psychosocial counseling and information-giving into their
      practice. Preparing genetic counseling students for clinical practice is a
      challenging task, particularly when helping them develop effective and active
      counseling skills. Resistance to incorporating these skills may stem from
      decreased confidence, fear of causing harm or a lack of clarity of psycho-social
      goals. The author reflects on the personal challenges experienced in teaching
      genetic counselling students to work with psychological and social complexity,
      and proposes a Genetic Counseling Adaptation Continuum model and methodology to
      guide students in the use of advanced counseling skills.

PMID- 27891552
TI  - Enteric glial cells are susceptible to Clostridium difficile toxin B.
AB  - Clostridium difficile causes nosocomial/antibiotic-associated diarrhoea and
      pseudomembranous colitis. The major virulence factors are toxin A and toxin B
      (TcdB), which inactivate GTPases by monoglucosylation, leading to cytopathic
      (cytoskeleton alteration, cell rounding) and cytotoxic effects (cell-cycle
      arrest, apoptosis). C. difficile toxins breaching the intestinal epithelial
      barrier can act on underlying cells, enterocytes, colonocytes, and enteric
      neurons, as described in vitro and in vivo, but until now no data have been
      available on enteric glial cell (EGC) susceptibility. EGCs are crucial for
      regulating the enteric nervous system, gut homeostasis, the immune and
      inflammatory responses, and digestive and extradigestive diseases. Therefore, we
      evaluated the effects of C. difficile TcdB in EGCs. Rat-transformed EGCs were
      treated with TcdB at 0.1-10 ng/ml for 1.5-48 h, and several parameters were
      analysed. TcdB induces the following in EGCs: (1) early cell rounding with Rac1
      glucosylation; (2) early G2/M cell-cycle arrest by cyclin B1/Cdc2 complex
      inactivation caused by p27 upregulation, the downregulation of cyclin B1 and Cdc2
      phosphorylated at Thr161 and Tyr15; and (3) apoptosis by a caspase-dependent but
      mitochondria-independent pathway. Most importantly, the stimulation of EGCs with
      TNF-alpha plus IFN-gamma before, concomitantly or after TcdB treatment strongly
      increased TcdB-induced apoptosis. Furthermore, EGCs that survived the cytotoxic
      effect of TcdB did not recover completely and showed not only persistent Rac1
      glucosylation, cell-cycle arrest and low apoptosis but also increased production
      of glial cell-derived neurotrophic factor, suggesting self-rescuing mechanisms.
      In conclusion, the high susceptibility of EGCs to TcdB in vitro, the increased
      sensitivity to inflammatory cytokines related to apoptosis and the persistence of
      altered functions in surviving cells suggest an important in vivo role of EGCs in
      the pathogenesis of C. difficile infection.

PMID- 27891555
TI  - The epidemiologic transition of thalassemia and associated hemoglobinopathies in
      southern Taiwan.
AB  - Since 1993, following the National Thalassemia Major Prevention Program and an
      increase in immigration and interracial marriages, especially in southern Taiwan,
      the distribution of hemoglobinopathies may have changed. This study investigates
      the epidemiologic transition of hemoglobinopathies. We analyzed 1870 specimens
      collected between 2003 and 2012 in southern Taiwan, used gap-polymerase chain
      reaction and PCR-restriction fragment length polymorphism-based methods, and
      confirmed genotypes of hemoglobinopathies by DNA sequencing. We found a 91%
      reduction in the incidence of thalassemia major compared with samples from
      between 1986 and 1995. The most common genotypes of alpha-thalassemia and alpha
      Hb variants were the SEA type (69.4%) and Hb Quong Sze (1.54%). The most common
      genotypes of beta-thalassemia and beta Hb variants were IVS-II-654 (46.2%) and Hb
      E (2.2%), respectively. Compared with studies performed in different areas of and
      time intervals in Taiwan, a higher prevalence of -alpha3.7, Hb Quong Sze, and Hb
      E and a lower prevalence of the SEA type were found in this study. However, the
      SEA type remained the most common genotype observed. In addition, an increasing
      number of cases with an -alpha3.7 type carrier, Hb Quong Sze carrier, and
      Ggamma(Agammadeltabeta) degrees  were identified following a peak of interracial
      marriages between 2003 and 2005, reflecting a regional difference and the impact
      of interracial marriage. In conclusion, global migration and international
      marriage have changed the distribution of hemoglobinopathies in Taiwan. A more
      comprehensive prenatal screening for new immigrants with a longer follow-up is
      warranted.

PMID- 27891556
TI  - Comparing Self-Regulation-Associated Event Related Potentials in Preschool
      Children with and without High Levels of Disruptive Behavior.
AB  - Deficient self-regulation plays a key role in the etiology of early onset
      disruptive behavior disorders and signals risk for chronic psychopathology.
      However, to date, there has been no research comparing preschool children with
      and without high levels of disruptive behavior using Event Related Potentials
      (ERPs) associated with specific self-regulation sub-processes. We examined 15
      preschool children with high levels of disruptive behavior (35 % female) and 20
      peers with low disruptive behavior (50 % female) who completed a Go/No-go task
      that provided emotionally valenced feedback. We tested whether 4 ERP components:
      the Error Related Negativity, the Error Positivity, the Feedback Related
      Negativity, and the No-go N2, differed in preschool children with and without
      high levels of disruptive behavior. Preschoolers with high levels of disruptive
      behavior showed less differentiation between the Error Positivity and
      corresponding waveforms following correct responses at posterior sites.
      Preschoolers with high and low disruptive behavior also showed differences in
      Go/No-go N2 waveform amplitudes across electrodes. These findings suggest that
      preschool children with high levels of disruptive behavior may show abnormal
      brain activity during certain self-regulation sub-processes, informing potential
      advances in conceptualizing and treating early disruptive behavior.

PMID- 27891557
TI  - Exogenous Expression of Nt-3 and TrkC Genes in Bone Marrow Stromal Cells Elevated
      the Survival Rate of the Cells in the Course of Neural Differentiation.
AB  - Bone marrow stromal cells (BMSCs) are attractive cellular sources for cell
      therapy of many diseases, specifically neurodegenerative ones. The potential
      capability of BMSCs could be further augmented by enhancing their neuroprotective
      property, differentiation potential, and survival rate subsequent to
      transplantation. Therefore, a concurrent upregulation of neurotrophin-3 (NT-3)
      and its high affinity receptor, tyrosin kinase C (TrkC), was utilized in our
      study. BMSCs were cotransfected with pDsRed1-N1-NT-3 and pCMX-TrkC plasmids
      before induction of neural differentiation. pEGFP-N1-transfected BMSCs were also
      employed as a control. Real-time quantitative reverse transcription polymerase
      chain reaction (qRT-PCR) was employed for gene expression analysis. Cell
      viability was evaluated by MTT assay, while apoptosis rate was assessed by flow
      cytometry after PI and Annexin V staining. NT-3 and TrkC mRNA levels were greatly
      elevated following cotransfection of cells with pDsRed1-N1-NT-3 and pCMX-TrkC
      vectors. The expression of neural markers (i.e., NFM, and NeuroD1) was augmented
      in cotransfected BMSCs, compared to the control ones, after neural induction. At
      each time point, the viability and apoptosis rates of the cells over-expressing
      NT-3 and TrkC showed increased and reduced patterns, respectively. Our data
      demonstrated that NT-3/TrkC-co-transfected BMSCs, compared to those of intact
      cells, could be more beneficial graft candidates for the upcoming treatment
      strategies of neurogenic disorders due to their increased viability and
      expression of neural markers. This may be due to their increased level of neural
      differentiation potential and/or their enhanced rate of survival and/or their
      useful capacity to secrete NT-3.

PMID- 27891558
TI  - Erratum to: An experimental study on the comparison of the effects of triester
      glycerol oxide on wound repair.

PMID- 27891559
TI  - Commentary on: "An update on peripheral ossifying fibroma: case report and
      literature review".

PMID- 27891560
TI  - Emergency femoral hernia repair: 13-year retrospective comparison of the three
      classical open surgical approaches.
AB  - PURPOSE AND METHODS: Femoral hernia repairs have been done classically with three
      different open approaches, namely the Lockwood's (LW), Lotheissen's (LT) and
      McEvedy's (ME) approaches. Current literature has yet provided any definite
      conclusion over the best approach in emergency situations. This study aims to
      evaluate and compare the operative outcomes of these three approaches in
      emergency situations by retrospectively analyzing 190 cases (76 ME, 33 LT, 81 LW)
      in 13 years at a regional surgical center. RESULTS: Significantly less
      laparotomies were required for McEvedy's approach (ME 2.6% vs LT 33.3% vs LW
      43.2%, p < 0.001), despite the need for bowel resection appear to be higher (ME
      43.4% vs LT 27.3% vs LW 27.2%, p = 0.072). Overall hernia recurrence (p = 0.657)
      and surgical complication rates (p = 0.585) were similar between the three
      approaches. Although not reaching statistical significance, it appeared that in
      patients undergoing McEvedy's operation, mean length of stay was longer (ME 10.1
      days vs LT 7.4 days vs LW 9.2 days, p = 0.407) and required more operation time
      (ME 97.4 min vs LT 72.0 min vs LW 79.0 min, p = 0.222). CONCLUSIONS: All three
      approaches were safe and effective in repairing femoral hernias in the emergency
      setting. McEvedy's approach may be superior to others when entry into the
      peritoneum is anticipated, although it may potentially be associated with longer
      operation time and hospital stay.

PMID- 27891561
TI  - Citrus psorosis virus coat protein-derived hairpin construct confers stable
      transgenic resistance in citrus against psorosis A and B syndromes.
AB  - Citrus psorosis virus (CPsV) is the causal agent of psorosis, a serious and
      widespread citrus disease. Two syndromes of psorosis, PsA and PsB, have been
      described. PsB is the most aggressive and rampant form. Previously, we obtained
      Pineapple sweet orange plants transformed with a hairpin construct derived from
      the CPsV coat protein gene (ihpCP). Some of these plants were resistant to CPsV
      90-1-1, a PsA isolate homologous to the transgene. In this study, we found that
      expression of the ihpCP transgene and siRNA production in lines ihpCP-10 and -15
      were stable with time and propagation. In particular, line ihpCP-15 has been
      resistant for more than 2 years, even after re-inoculation. The ihpCP plants were
      also resistant against a heterologous CPsV isolate that causes severe PsB
      syndrome. Line ihpCP-15 manifested complete resistance while line ihpCP-10 was
      tolerant to the virus, although with variable behaviour, showing delay and
      attenuation in PsB symptoms. These lines are promising for a biotech product
      aimed at eradicating psorosis.

PMID- 27891563
TI  - Erratum to: Harvesting of microalgae biomass from the phycoremediation process of
      greywater.

PMID- 27891562
TI  - Molecular genetic analysis and evolution of begomoviruses and betasatellites
      causing yellow mosaic disease of bhendi.
AB  - In India, Bhendi yellow vein mosaic disease (BYVMD) is one of the most
      economically important diseases of bhendi/okra and is caused by a complex of
      monopartite begomovirus (Bhendi yellow vein mosaic virus-BYVMV) and betasatellite
      (Bhendi yellow vein betasatellite-BYVB). In this study, we have analyzed the role
      of possible evolutionary factors involved in the evolution of BYVMV and BYVB
      isolates. Evidence of inter-species and inter-strain recombination events was
      detected among the viral isolates, and majority of these recombinant isolates
      possess microsatellites in their genome. Recombination analysis suggests that
      cotton-infecting and bhendi-infecting begomoviruses probably share a recent
      common ancestor. In addition to genetic differentiation and gene flow, high
      degree of genetic variability was detected among the viral population. A strong
      purifying selection seems to be acting on the viral coding regions. The
      nucleotide substitution rate of V1 gene (for BYVMV) and betaC1 gene (for BYVB)
      was estimated to be 7.55 * 10-4 and 2.25 * 10-3 nucleotide
      substitutions/site/year, respectively. The present study underlines that the
      evolution of BYVMD-associated viral components is driven by selection acting on
      the genetic variation generated by recombination and mutation.

PMID- 27891565
TI  - Expression and biochemical characteristics of two different aldosterone receptors
      in both healthy and dilated cardiomyopathy dog heart tissue.
AB  - Recently, replicates of the aldosterone receptor expression have been done in
      healthy heart dog tissues through immunohistochemistry, showing an apparent
      heterogeneous distribution in the four chambers. Recent studies have also
      identified immediate effects of aldosterone, suggesting aldosterone also produces
      non-genomic effects caused by an unidentified receptor. In order to study the
      molecular and quantitative expression characteristics of aldosterone binding
      receptors in the canine heart, we conducted studies, using Western Blot, in the
      heart from both healthy animals and animals with dilated cardiomyopathy. The
      results show the presence and distribution of two aldosterone receptors; one of
      110/120 kDa molecular weight, suggested as cytosolic/nuclear and the other of
      undetermined location with a 250 kDa molecular weight.

PMID- 27891564
TI  - A homozygous PIGN missense mutation in Soft-Coated Wheaten Terriers with a canine
      paroxysmal dyskinesia.
AB  - Hereditary paroxysmal dyskinesias (PxD) are a heterogeneous group of movement
      disorders classified by frequency, duration, and triggers of the episodes. A
      young-adult onset canine PxD has segregated as an autosomal recessive trait in
      Soft-Coated Wheaten Terriers. The medical records and videos of episodes from 25
      affected dogs were reviewed. The episodes of hyperkinesia and dystonia lasted
      from several minutes to several hours and could occur as often as >10/day. They
      were not associated with strenuous exercise or fasting but were sometimes
      triggered by excitement. The canine PxD phenotype most closely resembled
      paroxysmal non-kinesigenic dyskinesia (PNKD) of humans. Whole genome sequences
      were generated with DNA from 2 affected dogs and analyzed in comparison to 100
      control canid whole genome sequences. The two whole genome sequences from dogs
      with PxD had a rare homozygous PIGN:c.398C > T transition, which predicted the
      substitution of an isoleucine for a highly conserved threonine in the encoded
      enzyme. All 25 PxD-affected dogs were PIGN:c.398T allele homozygotes, whereas
      there were no c.398T homozygotes among 1185 genotyped dogs without known
      histories of PxD. PIGN encodes an enzyme involved in the biosynthesis of
      glycosylphosphatidylinositol (GPI), which anchors a variety of proteins including
      CD59 to the cell surface. Flow cytometry of PIGN-knockout HEK239 cells expressing
      recombinant human PIGN with the c.398T variant showed reduced CD59 expression.
      Mutations in human PIGN have been associated with multiple congenital anomalies
      hypotonia-seizures syndrome-1 (MCAHS1). Movement disorders can be a part of
      MCAHS1, but this is the first PxD associated with altered GPI anchor function.

PMID- 27891566
TI  - Sudden death associated with syndromic craniosynostosis.
AB  - In this paper we report the autopsy findings of a 7 year old girl who presented
      with headache, nausea and repeated vomiting and died unexpectedly at home. She
      had no previous history of major illnesses and no history of epileptic seizures.
      External examination revealed ocular abnormalities. Internal examination
      demonstrated severe cerebral edema with tonsillar herniation, premature fusion of
      the cranial bone sutures, and prominent convolutional markings of the inner table
      of the skull. Death was due to severe cerebral edema complicating syndromic
      craniosynostosis. The craniofacial features in this case were in keeping with a
      diagnosis of Crouzon syndrome which was confirmed by molecular testing of the
      FGFR2 gene. Crouzon syndrome is a genetic disorder characterized by premature
      fusion of the cranial bone sutures resulting in distinctive malformations of the
      craniofacial region.

PMID- 27891567
TI  - Barriers and Facilitators to Sustainment of an Evidence-Based Supported
      Employment Program.
AB  - Large-scale initiatives to expand evidence-based practices are often poorly
      implemented and rarely endure. The purpose of this study was to identify the
      perceived barriers and facilitators to sustainment of an evidence-based supported
      employment program, Individual Placement and Support (IPS). Within a 2-year
      prospective study of sustainment among 129 IPS programs in 13 states
      participating in a national learning community, we interviewed IPS team leaders
      and coded their responses to semi-structured interviews using a conceptual
      framework adapted from another large-scale implementation study. Leaders in 122
      agencies (95%) that sustained their IPS programs identified funding,
      prioritization, and workforce characteristics as both key facilitators and
      barriers. Additional key factors were lack of local community supports as a
      barrier and leadership and structured workflow as facilitators. Within the IPS
      learning community, team leaders attributed the sustainment of their program to
      funding, prioritization, workforce, agency leadership, and structured workflow.
      The actions of the learning community's leadership, state governments, and local
      programs together may have contributed to the high sustainment rate.

PMID- 27891568
TI  - Oral hygiene compliance in orthodontic patients: a randomized controlled study on
      the effects of a post-treatment communication.
AB  - BACKGROUND: Several studies have recently demonstrated that a post-treatment
      communication to explain the importance of an oral hygiene can improve the
      orthodontic patients' compliance over a period of 66 days. The main goal of this
      study is to evaluate the effects of a structured follow-up communication after
      orthodontic appliance application on oral hygiene compliance after 30-40 days.
      METHODS: Eighty-four orthodontic participants enrolled from patients who were
      beginning fixed orthodontic treatment at the Orthodontic Department, Gaslini
      Hospital, Genova, between July and October 2014 were randomly assigned to one of
      three trial arms. Before the bonding, all patients underwent a session of oral
      hygiene aimed at obtaining an plaque index of "zero." At the following
      orthodontic appointment, the plaque index was calculated for each patient in
      order to assess oral hygiene compliance. The first group served as control and
      did not receive any post-procedure communication, the second group received a
      structured text message giving reassurance, and the third group received a
      structured telephone call. Participants were blinded to group assignment and were
      not made aware that the text message or the telephone call was part of the study.
      (The research protocol was approved by the Italian Comitato Etico Regionale della
      Liguria-sezione 3^ c/o IRCCS-Istituto G. Gaslini 845/2014, and it is not
      registered in the trial's register.) RESULTS: Thirty patients were randomly
      assigned to the control group, 28 participants to the text message group, and 26
      to the telephone group. Participants who received a post-treatment communication
      reported higher level of oral hygiene compliance than participants in the control
      group. The plaque index was 0.3 (interquartile range (Iqr), 0.60) and 0.75 (Iqr,
      1.30), respectively, with a significant difference (P = 0.0205). CONCLUSIONS: A
      follow-up procedure after orthodontic treatment may be an effective tool to
      increase oral hygiene compliance also over a short period.

PMID- 27891569
TI  - Chair-side generated posterior monolithic lithium disilicate crowns: clinical
      survival after 6 years.
AB  - OBJECTIVES: The objective of this prospective clinical study was to evaluate the
      clinical performance of chair-side generated monolithic lithium disilicate crowns
      after 72 months. MATERIALS AND METHODS: Forty-one posterior full contour crowns
      made of lithium disilicate ceramic were inserted in 34 patients with a chair-side
      CAD/CAM technique. One crown per patient was randomly selected for evaluation at
      baseline, 6, 12, 24, 36, 48, 60 and 72 months according to the modified US Public
      Health Service criteria. RESULTS: After a mean examination time of 73.2 months
      (SD +/- 1.7 months), 25 crowns were available for re-examination. Within the
      observation period, three failures occurred due to one crown fracture after 2.9
      years, an abutment fracture after 6.0 years, and one severe endodontic problem
      after 6.1 years. One lithium disilicate crown showed a loss of retention after 2
      years but could be reinserted. There were two events of caries below the crown
      margin, one after 24 and another one after 48 months. Both teeth received
      cervical adhesive composite fillings. Two abutment teeth changed their
      sensibility perception from positive to negative within the first 13 months. The
      failure-free rate was 87.6%, and the complication-free rate was 70.1% after 6
      years according to the Kaplan-Meier analysis. CONCLUSIONS: Due to the fact that
      there was only one severe technical complication and the severe biological
      complications were in a normal range, the clinical performance of monolithic
      lithium disilicate crowns in the posterior region was completely satisfying.
      CLINICAL RELEVANCE: The chair-side application of monolithic lithium disilicate
      crowns can be recommended.

PMID- 27891570
TI  - Pragmatic approach to manage new oral anticoagulants in patients undergoing
      dental extractions: a prospective case-control study.
AB  - OBJECTIVES: The aim of this study was to validate a standardized pragmatic
      approach to manage new oral anticoagulants (NOACs) in patients who undergo dental
      extractions. MATERIALS AND METHODS: This prospective case-control study in
      patients undergoing dental extraction included 26 patients (mean age 76 years,
      57% male) treated with dabigatran, rivaroxaban, or apixaban and 26 matched
      controls. Regardless of timing of extraction, drug regimen, or renal function,
      patients were instructed to skip only the dose on the morning of the procedure. A
      procedural bleeding score was recorded and early and delayed bleeding was
      assessed at day 1 and day 7. Bleeding events were compared with a prospectively
      matched control group not taking any antithrombotic drug. RESULTS: There was no
      difference in the procedural bleeding score or in early bleeding events (5 in
      both groups). However, delayed bleeding occurred more frequently in
      anticoagulated compared to non-anticoagulated patients (7 versus none, p = 0.01).
      CONCLUSIONS: Skipping the morning dose of NOACs avoids excess bleeding during and
      early after the procedure. However, anticoagulated patients had an increased risk
      of delayed bleedings. Further study is needed to determine the optimal post
      procedural management. CLINICAL RELEVANCE: This is the first prospective study
      for the management of patients on NOACs undergoing dental extraction. Our
      pragmatic approach, omitting only a single morning dose, can guide clinical
      practice. Both patients and physicians should be aware of the increased delayed
      bleeding risk.

PMID- 27891571
TI  - High-Risk Medications in Hospitalized Elderly Adults: Are We Making It Easy to Do
      the Wrong Thing?
AB  - OBJECTIVES: To examine dosages of high-risk medications administered to elderly
      adults who fall in the hospital and to determine whether electronic default doses
      are appropriate for elderly adults. DESIGN: Retrospective. SETTING: Large urban
      academic hospital. PARTICIPANTS: Individuals aged 65 and older experiencing a
      fall. MEASUREMENTS: Prescribed daily dosages and use of high-risk medications
      (opiates, benzodiazepines, benzodiazepine-receptor agonists (BRAs), sleep
      medications, muscle relaxants, antipsychotics) administered within 24 hours
      before a fall were ascertained and compared with published recommended dosages
      for older adults and the hospital's electronic medical record (EMR) default doses
      for these drugs. RESULTS: Of 328 falls, 62% occurred in individuals administered
      at least one high-risk medication within the 24 hours before the fall, with 16%
      of the falls involving individuals receiving two, and another 16% in individuals
      receiving three or more. High-risk medications were often administered at higher
      than-recommended geriatric daily doses, in particular benzodiazepines and BRAs,
      for which the dose was higher than recommended in 29 of 51 cases (57%). Hospital
      EMR default doses were higher than recommended for 41% (12/29) of medications
      examined. CONCLUSION: High-risk medications were administered to older fallers.
      Doses administered and EMR default doses were often higher than recommended.
      Decreasing EMR default doses for individuals aged 65 and older and warnings about
      the cumulative numbers of high-risk medications prescribed per person may be
      simple interventions that could decrease inpatient falls.

PMID- 27891572
TI  - Safety concerns and risk management of multiple sclerosis therapies.
AB  - Currently, more than ten drugs have been approved for treatment of relapsing
      remitting multiple sclerosis (MS). Newer treatments may be more effective, but
      have less favorable safety record. Interferon-beta preparations and glatiramer
      acetate treatment require frequent subcutaneous or intramuscular injections and
      are only moderately effective, but have very rarely life-threatening adverse
      effects, whereas teriflunomide and dimethyl fumarate are administered orally and
      have equal or better efficacy, but have more potentially severe adverse effects.
      The highly effective therapies fingolimod, natalizumab, daclizumab, and
      alemtuzumab have more serious adverse effects, some of which may be life
      threatening. The choice between drugs should be based on a benefit-risk
      evaluation and tailored to the individual patient's requirements in a dialogue
      between the patient and treating neurologist. Patients with average disease
      activity can choose between dimethyl fumarate and teriflunomide or the "old
      injectable." Patients with very active MS may choose a more effective drug as the
      initial treatment. In case of side effects on one drug, switch to another drug
      can be tried. Suboptimal effect of the first drug indicates escalation to a
      highly efficacious drug. A favorable benefit-risk balance can be maintained by
      appropriate patient selection and appropriate risk management on therapy. New
      treatments will within the coming 1-2 years change our current treatment
      algorithm for relapsing-remitting MS.

PMID- 27891573
TI  - Nephrocheck(r) results should be corrected for dilution.

PMID- 27891574
TI  - Termination of pre-hospital resuscitation by anaesthesiologists - causes and
      consequences. A retrospective study.
AB  - AIM: Differentiating between a newly deceased patient and the lifeless patient in
      whom immediate resuscitation is required may be facilitated by a pre-hospital
      anaesthesiologist. The purpose of our study was to investigate to what extent and
      why the pre-hospital anaesthesiologist pronounced life extinct in situations
      where an emergency medical technician (EMT) would have been required to
      resuscitate. METHODS: All lifeless patients seen pre-hospitally by the
      anaesthesiologist-manned Mobile Emergency Care Unit in Odense, Denmark, from 2010
      to 2014 were retrospectively studied. RESULTS: Of 17 035 contacts, 1275 patients
      were lifeless without reliable signs of death. In 642 of these patients (3.8%)
      resuscitation was initiated (median age 68 years). The remaining 633 patients
      (3.7%) were declared dead at the scene without any resuscitation attempt (median
      age 77 years). These latter patients would have been attempted resuscitated, had
      the anaesthesiologist not been present. In 54.5% of cases where documentation was
      available in the patient records, reasons for not resuscitating these patients
      included time elapsed from incident to contact with physician, 'overall
      assessment', chronic disease, or do-not-resuscitate order. CONCLUSION: In one
      patient in 30, the MECU refrained from futile resuscitation in cases where
      legislation required an EMT to initiate resuscitation. This practice reduced
      unethical attempts of resuscitation, reduced unnecessary emergency ambulance
      transports, and reduced the work load of the hospital resuscitation teams for one
      unnecessary alarm every third day. Differentiating between lifeless patients and
      dead patients not exhibiting reliable signs of death, however, is a complex task
      which is only sparsely documented.

PMID- 27891575
TI  - Multiple Sclerosis impact on employment and income in New Zealand.
AB  - BACKGROUND AND OBJECTIVES: We investigated the demographic, social and clinical
      characteristics associated with employment status and income for people with
      multiple sclerosis (MS) in New Zealand (NZ). METHODS: The NZ National MS
      Prevalence study included all persons resident in NZ on census day 2006 diagnosed
      with MS (96.7% coverage). Factors associated with employment and income status
      among the working age population (25-64 years) were identified by linear
      regression. RESULTS: Over 90% of working age people with MS (n=1727) had a work
      history, but 54% were not working. Work loss occurred early in the disease
      course, and at low disability (P<.001). Advancing age, progressive disease,
      longer disease duration, higher disability levels, partner loss and lower
      education were associated with work loss (P<.001). Working age people with MS had
      lower income than the NZ population (P<.0001). Higher qualifications yielded no
      additional income for MS females and about half the additional income for MS
      males (P<.0001). CONCLUSIONS: MS profoundly reduces employment and income early
      in the disease course, and at low levels of disability, however, unemployment is
      not entirely accounted for by clinical, social and demographic factors. These
      findings suggest social supports should be explored early in the disease course
      to reduce loss of income and unemployment for people with MS.

PMID- 27891576
TI  - Changes in Drug Use and Polypharmacy After the Age of 90: A Longitudinal Study of
      the Danish 1905 Cohort.
AB  - OBJECTIVES: To determine the longitudinal development of drug use in very old
      adults. DESIGN: Longitudinal cohort study with waves in 1998, 2000, 2002, and
      2005. SETTING: Nationwide study in Denmark. PARTICIPANTS: All living Danes born
      in 1905 were approached in 1998; 2,262 responded at baseline. MEASUREMENTS: Self
      reported use of regularly taken drugs. Mean and median number of drugs and growth
      curve models were used to identify the change in number of drugs as the cohort
      aged from 92 to 100. RESULTS: The within-person use of drugs increased with age
      for women (0.19 per year; 95% confidence interval (CI) = 0.15-0.24) and men (0.15
      per year; 95% CI = 0.06-0.24). Persons leaving the study prematurely had higher
      baseline values and a steeper increase in their annual use of drugs. The
      population-level mean number of drugs increased from baseline (3.6 drugs) to the
      first follow-up (4.1 drugs) but thereafter remained stable at approximately 4
      drugs. Women used more drugs than men at all waves. CONCLUSION: In this first
      longitudinal study of drug use in nonagenarians, individuals used an increasing
      number of drugs as they aged. This increase is difficult to detect in cross
      sectional analyses of the population-level mean. More efforts to understand what
      is reasonable prescribing at these older ages are needed.

PMID- 27891577
TI  - Statin use and risk of endometrial cancer: a nationwide registry-based case
      control study.
AB  - INTRODUCTION: Laboratory and epidemiological evidence have suggested that statin
      use may protect against the development of certain cancers, including endometrial
      cancer. In a nationwide registry-based case-control study, we examined the
      association between statin use and risk of endometrial cancer. MATERIAL AND
      METHODS: Cases were female residents of Denmark with a primary diagnosis of
      endometrial cancer during 2000-2009. For each case, we selected 15 female
      population controls matched on date of birth (+/-one month) using risk-set
      sampling. Ever use of statin was defined as two or more prescriptions on separate
      dates. Conditional logistic regressions were used to estimate age-matched (by
      design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals
      (CI) for endometrial cancer associated with statin use. The multivariable
      adjusted models included parity, hormone replacement therapy (HRT), obesity,
      diabetes, chronic obstructive pulmonary disease and education. We evaluated
      whether the association between statin use and endometrial cancer varied with
      duration and intensity of statin use, type of endometrial cancer or patient
      characteristics. RESULTS: The study population comprised 5382 endometrial cancer
      cases and 72 127 population controls. We observed no association between ever use
      of statins and endometrial cancer risk (OR 1.03, 95% CI 0.94-1.14). In addition,
      endometrial cancer risk did not vary substantially with duration or intensity of
      statin use. Stratification by type of endometrial cancer also yielded neutral
      ORs. CONCLUSIONS: In our nationwide case-control study, we found no association
      between statin use and risk of endometrial cancer.

PMID- 27891579
TI  - Unexpected motor weakness following quadratus lumborum block for gynaecological
      laparoscopy.
AB  - Quadratus lumborum block has recently been described as an effective and long
      lasting analgesic strategy for various abdominal operations, including
      gynaecological laparoscopy. Despite evidence that the analgesic effect is
      mediated by indirect paravertebral block and that local anaesthetic spreads to
      the lumbar paravertebral space, there have been no reports to date of lower limb
      motor weakness. We present a patient with unilateral hip flexion and knee
      extension weakness leading to unplanned overnight admission following lateral
      quadratus lumborum block with 20 ml levobupivacaine 0.25%. The L2 dermatomal
      sensory loss and hip flexion weakness suggested spread to either the L2
      paravertebral space or to the lumbar plexus, causing weakness of the psoas and
      iliacus muscles and possibly the quadriceps. The duration of motor block was
      approximately 18 h. This complication should be considered when performing the
      block, especially in the setting of day-case surgery.

PMID- 27891578
TI  - Dual specificity phosphatase 15 regulates Erk activation in Schwann cells.
AB  - Schwann cells and oligodendrocytes are the myelinating cells of the peripheral
      and central nervous system, respectively. Despite having different myelin
      components and different transcription factors driving their terminal
      differentiation there are shared molecular mechanisms between the two. Sox10 is
      one common transcription factor required for several steps in development of
      myelinating glia. However, other factors are divergent as Schwann cells need the
      transcription factor early growth response 2/Krox20 and oligodendrocytes require
      Myrf. Likewise, some signaling pathways, like the Erk1/2 kinases, are necessary
      in both cell types for proper myelination. Nonetheless, the molecular mechanisms
      that control this shared signaling pathway in myelinating cells remain only
      partially characterized. The hypothesis of this study is that signaling pathways
      that are similarly regulated in both Schwann cells and oligodendrocytes play
      central roles in coordinating the differentiation of myelinating glia. To address
      this hypothesis, we have used genome-wide binding data to identify a relatively
      small set of genes that are similarly regulated by Sox10 in myelinating glia. We
      chose one such gene encoding Dual specificity phosphatase 15 (Dusp15) for further
      analysis in Schwann cell signaling. RNA interference and gene deletion by genome
      editing in cultured RT4 and primary Schwann cells showed Dusp15 is necessary for
      full activation of Erk1/2 phosphorylation. In addition, we show that Dusp15
      represses expression of several myelin genes, including myelin basic protein. The
      data shown here support a mechanism by which early growth response 2 activates
      myelin genes, but also induces a negative feedback loop through Dusp15 to limit
      over-expression of myelin genes.

PMID- 27891580
TI  - Acute infection with the intestinal parasite Trichuris muris has long-term
      consequences on mucosal mast cell homeostasis and epithelial integrity.
AB  - A hallmark of parasite infection is the accumulation of innate immune cells,
      notably granulocytes and mast cells, at the site of infection. While this is
      typically viewed as a transient response, with the tissue returning to steady
      state once the infection is cleared, we found that mast cells accumulated in the
      large-intestinal epithelium following infection with the nematode Trichuris muris
      and persisted at this site for several months after worm expulsion. Mast cell
      accumulation in the epithelium was associated with the induction of type-2
      immunity and appeared to be driven by increased maturation of local progenitors
      in the intestinal lamina propria. Furthermore, we also detected increased local
      and systemic levels of the mucosal mast cell protease MCPt-1, which correlated
      highly with the persistent epithelial mast cell population. Finally, the mast
      cells appeared to have striking consequences on epithelial barrier integrity, by
      regulation of gut permeability long after worm expulsion. These findings
      highlight the importance of mast cells not only in the early phases of infection
      but also at later stages, which has functional implications on the mucosal
      tissue.

PMID- 27891581
TI  - Antigen specificity determines anti-red blood cell IgG-Fc alloantibody
      glycosylation and thereby severity of haemolytic disease of the fetus and
      newborn.
AB  - Haemolytic disease of the fetus and newborn (HDFN) is a severe disease in which
      fetal red blood cells (RBC) are destroyed by maternal anti-RBC IgG
      alloantibodies. HDFN is most often caused by anti-D but may also occur due to
      anti-K, -c- or -E. We recently found N-linked glycosylation of anti-D to be
      skewed towards low fucosylation, thereby increasing the affinity to IgG-Fc
      receptor IIIa and IIIb, which correlated with HDFN disease severity. Here, we
      analysed 230 pregnant women with anti-c, -E or -K alloantibodies from a
      prospective screening cohort and investigated the type of Fc-tail glycosylation
      of these antibodies in relation to the trigger of immunisation and pregnancy
      outcome. Anti-c, -E and -K show - independent of the event that had led to
      immunisation - a different kind of Fc-glycosylation compared to that of the total
      IgG fraction, but with less pronounced differences compared to anti-D. High Fc
      galactosylation and sialylation of anti-c correlated with HDFN disease severity,
      while low anti-K Fc-fucosylation correlated with severe fetal anaemia. IgG-Fc
      glycosylation of anti-RBC antibodies is shaped depending on the antigen. These
      features influence their clinical potency and may therefore be used to predict
      severity and identify those needing treatment.

PMID- 27891582
TI  - Versatile Roles of Intracellularly Located TRPV1 Channel.
AB  - The ubiquitous expression in many organs throughout the body and the ability to
      respond to a wide variety of physical and chemical stimuli have brought transient
      receptor potential (TRP) channels to the vanguards of our sensory systems. TRP
      vanilloid-1 (TRPV1) is the founding member of the TRPV subfamily. TRPV1 can be
      activated by noxious heat, protons, and vanilloids. Previous studies have shown
      that TRPV1 is located on the plasma membrane, serving to non-selectively permeate
      calcium ion from the extracellular region to the cytoplasm. Interestingly,
      increasing evidence suggests that TRPV1 is also located intracellularly in
      various cell types such as neurons, myocytes, and numerous cancer cells. By
      immunocytochemistry and/or fractionation followed by Western blotting, TRPV1 was
      found to express on the endoplasmic reticulum/sarcoplasmic reticulum and the
      mitochondria. By using various pharmacological and molecular tools, intracellular
      TRPV1 was also found to functionally express to control calcium level both inside
      the organelles and in the cytoplasm. Recent studies have shown that
      intracellularly located TRPV1 serves versatile functions in various physiological
      and pathological conditions (e.g., exercise endurance and hypertrophy). In this
      review, we not only have summarized the well-characterized roles of TRPV1, but
      also have highlighted the increasing importance of intracellular TRPV1-mediated
      pathways. Lastly, we have pointed out future research direction for answering
      several important questions that have remained unanswered. Vigorous investigation
      of the emerging roles of intracellular TRPV1 can allow a better understanding of
      how TRPV1 controls the cellular calcium homeostasis and its role in various
      physiological and pathophysiological conditions. J. Cell. Physiol. 232: 1957
      1965, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27891583
TI  - The use of anthracyclines in the treatment of endemic Burkitt lymphoma.
AB  - Burkitt lymphoma is the most common malignancy in children in Malawi, the world's
      poorest country, where there is a long history of treating this disease using a
      28-day cyclophosphamide-based protocol. Stage III/IV disease has had poor
      outcomes. In an attempt to improve the outcome for higher stage disease,
      anthracyclines were added to the existing protocol. The disease-free (DFS) and
      overall survival (OS) of 58 children with cytologically confirmed Burkitt
      lymphoma admitted during 2012-2014 and treated using this protocol were
      calculated. Six (10%) children had stage I disease, ten (17%) stage II and 42
      stage III or IV (73%). Overall 12-month DFS (OS) was 68.5% (72.9%); for stage I
      disease 100% (100%), stage II 56.2% (60%), stage III/IV 66.3% (72.2%). The DFS
      was significantly improved from the previous protocol (P = 8 * 10-4 ). The
      addition of doxorubicin to stage III and IV disease resulted in a markedly
      improved DFS. Anthracyclines are deliverable in resource-poor settings and
      possibly improve the survival of children with Burkitt lymphoma.

PMID- 27891584
TI  - An observational study of the macro- and micro-haemodynamic implications of
      epidural anaesthesia in children.
AB  - The haemodynamic implications of epidural anaesthesia in children are poorly
      documented. We report macro- and micro-haemodynamic data from an observational
      study of 25 children ranging from neonates to six-years old, who underwent
      surgery conducted with a specific combination of monitoring systems. We analysed
      90 min of study-related monitoring after epidural catheterisation, with skin
      incision taking place after around 30 min. We recorded macrohaemodynamic
      parameters (monitored using LiDCOrapid) including heart rate, mean arterial
      pressure, cardiac output, stroke volume, systemic vascular resistance and stroke
      volume variation. Microhaemodynamic parameters (monitored using InvosTM) included
      cerebral and peri-renal oxygenation. Based on the entire 90 min of study-related
      monitoring, we found significant increases in cardiac output (p = 0.009), stroke
      volume (p = 0.006) and stroke volume variation (p = 0.008), as well as decreases
      in systemic vascular resistance (p = 0.007) around 30 min after epidural
      blockade. There were no significant changes in heart rate, arterial pressure and
      cerebral or peri-renal oxygenation during these 90 min. Considering that the
      microhaemodynamic parameters were not affected by the macrohaemodynamic changes,
      we conclude that autoregulation of the brain and the kidneys was maintained in
      children under epidural anaesthesia.

PMID- 27891585
TI  - Novel mutations in KARS cause hypertrophic cardiomyopathy and combined
      mitochondrial respiratory chain defect.
AB  - Mutations in KARS, which encodes for both mitochondrial and cytoplasmic lysyl
      tRNA synthetase, have been so far associated with three different phenotypes: the
      recessive form of Charcot-Mary-Tooth polyneuropathy, the autosomal recessive
      nonsyndromic hearing loss and the last recently described condition related to
      congenital visual impairment and progressive microcephaly. Here we report the
      case of a 14-year-old girl with severe cardiomyopathy associated to mild
      psychomotor delay and mild myopathy; moreover, a diffuse reduction of cytochrome
      C oxidase (COX, complex IV) and a combined enzymatic defect of complex I (CI) and
      complex IV (CIV) was evident in muscle biopsy. Using the TruSight One sequencing
      panel we identified two novel mutations in KARS. Both mutations, never reported
      previously, occur in a highly conserved region of the catalytic domain and
      displayed a dramatic effect on KARS stability. Structural analysis confirmed the
      pathogenic role of the identified variants. Our findings confirm and emphasize
      that mt-aminoacyl-tRNA synthetases (mt-ARSs) enzymes are related to a broad
      clinical spectrum due to their multiple and still unknown functions.

PMID- 27891586
TI  - Celastrol Attenuates Cadmium-Induced Neuronal Apoptosis via Inhibiting Ca2+ 
      CaMKII-Dependent Akt/mTOR Pathway.
AB  - Cadmium (Cd), an environmental and industrial pollutant, affects the nervous
      system and consequential neurodegenerative disorders. Recently, we have shown
      that celastrol prevents Cd-induced neuronal cell death partially by suppressing
      Akt/mTOR pathway. However, the underlying mechanism remains to be elucidated.
      Here, we show that celastrol attenuated Cd-elevated intracellular-free calcium
      ([Ca2+ ]i ) level and apoptosis in neuronal cells. Celastrol prevented Cd-induced
      neuronal apoptosis by inhibiting Akt-mediated mTOR pathway, as inhibition of Akt
      with Akt inhibitor X or ectopic expression of dominant negative Akt reinforced
      celastrol's prevention of Cd-induced phosphorylation of S6K1/4E-BP1 and cell
      apoptosis. Furthermore, chelating intracellular Ca2+ with BAPTA/AM or preventing
      [Ca2+ ]i elevation using EGTA potentiated celastrol's repression of Cd-induced
      [Ca2+ ]i elevation and consequential activation of Akt/mTOR pathway and cell
      apoptosis. Moreover, celastrol blocked Cd-elicited phosphorylation of CaMKII, and
      pretreatment with BAPTA/AM or EGTA enhanced celastrol's suppression of Cd
      increased phosphorylation of CaMKII in neuronal cells, implying that celastrol
      hinders [Ca2+ ]i -mediated CaMKII phosphorylation. Inhibiting CaMKII with KN93 or
      silencing CaMKII attenuated Cd activation of Akt/mTOR pathway and cell apoptosis,
      and this was strengthened by celastrol. Taken together, these data demonstrate
      that celastrol attenuates Cd-induced neuronal apoptosis via inhibiting Ca2+ 
      CaMKII-dependent Akt/mTOR pathway. Our findings underscore that celastrol may act
      as a neuroprotective agent for the prevention of Cd-induced neurodegenerative
      disorders. J. Cell. Physiol. 232: 2145-2157, 2017. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27891587
TI  - Intestinal mononuclear cells primed by systemic interleukin-12 display long-term
      ability to aggravate colitis in mice.
AB  - To address whether the burst of systemic interleukin-12 (IL-12) influences
      intestinal inflammation elicited by luminal stimuli, we induced IL-12 release by
      cDNA injection in C57BL/6 mice and simultaneously started dextran sulphate sodium
      administration. The sequence of the inflammatory response triggered by IL-12
      release was characterized by assessing myeloperoxidase activity and histological
      damage in colon samples on days 1, 3, 5 and 7 after colitis induction. To
      evaluate the persistence of IL-12 priming, colitis was induced in mice 7 or 60
      days after cDNA injection. Under IL-12 influence, the development of acute
      colitis presented a faster and selective infiltration of inflammatory mononuclear
      cells in the lamina propria. Recruitment was driven by systemic cytokines rather
      than luminal antigens. Interestingly, when colitis was triggered 7 or 60 days
      after the cytokine storm, cells maintained the ability to worsen clinical signs
      of intestinal inflammation. Together, a systemic IL-12 burst effectively primed
      intestinal cells that became more prone to develop inflammatory responses.
      Activation was long-lasting because intestinal cells maintained their
      inflammatory potential and their ability to aggravate colitis.

PMID- 27891588
TI  - Whole-body MRI reveals high incidence of osteonecrosis in children treated for
      Hodgkin lymphoma.
AB  - Osteonecrosis is a well-recognized complication in patients treated with
      corticosteroids. The incidence of osteonecrosis in children treated for Hodgkin
      lymphoma is unknown because prospective whole-body magnetic resonance imaging
      (MRI) studies are lacking in this patient population. Paediatric patients with
      newly diagnosed Hodgkin lymphoma who were treated according to a uniform
      paediatric Hodgkin protocol were eligible for inclusion in this prospective
      study. Whole-body MRI was performed in all 24 included patients (mean age 15.1
      years, 12 girls) both before treatment and after 2 cycles of chemotherapy, and in
      16 patients after completion of chemotherapy. Osteonecrosis was identified in 10
      patients (41.7%, 95% confidence interval: 22.0-61.4%), with a total of 56
      osteonecrotic sites. Osteonecrosis was detected in 8 patients after 2 cycles of
      OEPA (vincristine, etoposide, prednisone, doxorubicin), and in 2 additional
      patients after completion of chemotherapy. Epiphyseal involvement of long bones
      was seen in 4 of 10 children. None of the patients with osteonecrosis had any
      signs of bone collapse at the times of scanning. Whole-body MRI demonstrates
      osteonecrosis to be a common finding occurring during therapy response assessment
      of paediatric Hodgkin lymphoma. Detection of early epiphyseal osteonecrosis could
      allow for treatment before bone collapse and joint damage may occur.

PMID- 27891589
TI  - Critical roles of conventional dendritic cells in promoting T cell-dependent
      hepatitis through regulating natural killer T cells.
AB  - Dendritic cells (DCs) play critical roles in initiating and regulating innate
      immunity as well as adaptive immune responses. However, the role of conventional
      dendritic cells (cDCs) in concanavalin A (ConA)-induced fulminant hepatitis is
      unknown. In this study, we demonstrated that depletion of cDCs using either CD11c
      diphtheria toxin receptor transgenic mice (DTR Tg) mice or anti-CD11c antibody
      reduced the severity of liver injury significantly, indicating a detrimental role
      of cDCs in ConA-induced hepatitis. We elucidated further the pathological role of
      cDCs as being the critical source of interleukin (IL)-12, which induced the
      secretion of interferon (IFN)-gamma by natural killer (NK) T cells.
      Reconstitution of cDCs-depleted mice with IL-12 restored ConA-induced hepatitis
      significantly. Furthermore, we determined that NK T cells were the target of DC
      derived IL-12, and NK T cells contributed to liver inflammation and injury
      through production of IFN-gamma. In summary, our study demonstrated a novel
      function of cDCs in mediating ConA-induced hepatitis through regulating IFN-gamma
      secretion of NK T cells in an IL-12-dependent fashion. Targeting cDCs might
      provide potentially therapeutic applications in treating autoimmune related liver
      diseases.

PMID- 27891590
TI  - Bi-allelic IARS mutations in a child with intra-uterine growth retardation,
      neonatal cholestasis, and mild developmental delay.
AB  - Recently, bi-allelic mutations in cytosolic isoleucyl-tRNA synthetase (IARS) have
      been described in three individuals with growth delay, hepatic dysfunction, and
      neurodevelopmental disabilities. Here we report an additional subject with this
      condition identified by whole-exome sequencing. Our findings support the
      association between this disorder and neonatal cholestasis with distinct liver
      pathology. Furthermore, we provide functional data on two novel missense
      substitutions and expand the phenotype to include mild developmental delay, skin
      hyper-elasticity, and hypervitaminosis D.

PMID- 27891591
TI  - NOR1 Suppresses Cancer Stem-Like Cells Properties of Tumor Cells via the
      Inhibition of the AKT-GSK-3beta-Wnt/beta-catenin-ALDH1A1 Signal Circuit.
AB  - Cancer stem cells (CSCs) play a key role in tumor radiotherapy and chemotherapy
      resistance, relapse, and metastasis, and are primarily maintained in a resting
      state in vivo. The failure of conventional therapies to target CSCs is the main
      cause of treatment failure. The discovery of CSCs in nasopharyngeal carcinoma
      (NPC) tumors is becoming more prevalent; however, the understanding of the
      mechanisms underlying the maintenance of tumor stemness is still limited. We
      previously cloned NOR1, a tumor suppressor gene downregulated in NPC cell lines
      and tissues. In this study, we demonstrate that Wnt/beta-catenin and ALDH1A1 form
      a signal circuit and that NOR1 antagonizes the tumor stem cell-like phenotype in
      NPC cell lines: the ectopic overexpression of NOR1 reduced beta-catenin and
      ALDH1A1 expression; beta-catenin/TCF4 targeted the regulation of ALDH1A1
      transcription in NPC cells; silencing ALDH1A1 reduced AKT (total and
      phosphorylated) and GSK-3beta (phosphorylated) expression; and eventually
      feedback decreased beta-catenin expression levels. We also found that NOR1
      expression decreased cancer stem-like cell properties of NPC cells, reduced their
      ability to form tumor spheroids in vitro, reduced tumorigenicity in nude mice in
      vivo, and increased sensitivity to chemotherapy agents. Taken together, our
      findings illustrated a new function of NOR1 that suppresses cancer stem-like cell
      properties in tumor cells by inhibiting the AKT-GSK-3beta-Wnt/beta-catenin
      ALDH1A1 signal circuit. The study suggests that NOR1 deletion expression in NPC
      cells may be a potential molecular target for cancer stem cell therapy. J. Cell.
      Physiol. 232: 2829-2840, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27891592
TI  - Evaluation of a cow-side milk progesterone assay and assessment of the positive
      predictive value of oestrus diagnosis by dairy farmers in New South Wales.
AB  - OBJECTIVES: The three objectives of this study were to determine the positive
      predictive value (PPV) of oestrus diagnosis (heat detection accuracy) by dairy
      farmers, calculate the diagnostic sensitivity and specificity of the P4 Rapid
      milk progesterone assay for detecting a corpus luteum and evaluate the economics
      of using a cow-side milk progesterone assay designed to aid oestrus diagnosis.
      METHODS: Milk samples were collected from 752 cows diagnosed in oestrus by farm
      personnel on 14 dairy farms. Samples were tested using the P4 Rapid milk
      progesterone assay to estimate the PPV of oestrus diagnosis at each farm and a
      crude pooled mean of PPV of oestrus diagnosis across all farms. A further 156
      milk samples were collected from cows with luteal tissue status determined by
      transrectal ultrasound and tested by the P4 Rapid assay to enable calculation of
      the sensitivity and specificity of the P4 Rapid assay. RESULTS: For pooled farm
      samples, the PPV was 97.0%, with a range between farms of 88.9-100%. Sensitivity
      of the P4 Rapid milk progesterone assay for detecting a corpus luteum was 90.1%
      and specificity was 98.7%. Misclassification of oestrus in cows previously
      identified as pregnant was the most common cause of false-positive oestrus
      diagnoses by farm personnel. CONCLUSION: Routine testing of milk progesterone in
      all cows diagnosed in oestrus is not economically justified and may even slightly
      reduce submission rates; conversely, strategic use of cow-side milk progesterone
      assays can improve herd reproductive performance by facilitating decisions on
      whether to rebreed cows previously diagnosed as pregnant.

PMID- 27891594
TI  - Obituary: Anthony William English.

PMID- 27891593
TI  - Remote chemical immobilisation method for free-ranging Australian cattle.
AB  - BACKGROUND: Many situations are encountered in Australia where the capture and
      restraint of free-ranging cattle (Bos taurus/Bos indicus) is required. Chemical
      immobilisation via darting is a potentially useful tool for managing and
      researching large wild herbivores; however, there is no reliable method for its
      application to Australian cattle. The aim of this study was to develop an
      efficacious, humane, cost-effective ground darting method for free-ranging
      cattle. METHODS: The 30 female cattle were darted and captured on a pastoral
      station in north-west Australia from a vehicle. Xylazine (0.59 mg/kg) and
      ketamine (3.59 mg/kg) were used to capture animals and yohimbine (0.10 mg/kg) was
      used as an antagonist to xylazine to reduce recumbent time. RESULTS: Cattle
      became recumbent at a mean time of 8 min and a mean distance of 260 m from
      darting. The mortality rate was zero on the day of capture and 7% at 14 days post
      capture. CONCLUSIONS: The majority of darted cattle were successfully immobilised
      with one dart and recovered within 30 min, with consumables costing approximately
      A$30 per captured animal. The technique developed represents a rapid and humane
      method for capturing free-ranging cattle and, with consideration for legislation
      surrounding use of veterinary chemicals, could be applied in many contexts across
      Australia.

PMID- 27891598
TI  - Donald Joseph McCaffrey 1935 - 2016.

PMID- 27891599
TI  - Caroline Hopkins (nee Perrin) 1972-2016.

PMID- 27891595
TI  - Comparison of the use of sodium carbonate (washing soda crystals) and apomorphine
      for inducing emesis in dogs.
AB  - OBJECTIVE: To describe the use of sodium carbonate and apomorphine in a
      historical cohort of dogs, compare the occurrence of emesis and report any
      adverse effects recorded. METHODS: This historical, observational study included
      information from medical records of dogs that received an emetic agent. The
      occurrence of emesis with apomorphine or sodium carbonate was calculated and the
      association between emesis and agent was explored, with the odds ratio and 95%
      confidence interval (CI) reported. A non-inferiority analysis of the occurrence
      of emesis for sodium carbonate was performed against an equivalence range of +/
      7% of the estimated occurrence of emesis with apomorphine. Owners were emailed a
      short survey about their dog's health after their visit to the hospital for
      induced emesis. RESULTS: Records for 787 dogs seen from January 2007 to December
      2013 were included. For apomorphine, 382/392 dogs showed emesis (97%, 95% CI 95
      100%). For sodium carbonate, 320/395 dogs showed emesis (81%, 95% CI 77-85%),
      which fell below the equivalence range for apomorphine (97 +/- 7%, 90-100%) and
      was considered inferior. The odds ratio of emesis with apomorphine to sodium
      carbonate was 9.0 (95% CI 4.6-17.6). Of 18 responses to the survey, 5 reported
      abnormalities after emesis (3 with sodium carbonate, 2 with apomorphine).
      CONCLUSION: The occurrence of emesis with sodium carbonate was high but inferior
      to apomorphine. However, the advantages of sodium carbonate, including less
      expense and ease of accession compared with apomorphine, make it a viable choice
      in emergency medicine.

PMID- 27891601
TI  - Shedding light on hematopoietic stem cells: formation, regulation, and
      utilization.

PMID- 27891600
TI  - Human pDCs display sex-specific differences in type I interferon subtypes and
      interferon alpha/beta receptor expression.
AB  - The outcomes of many diseases differ between women and men, with women
      experiencing a higher incidence and more severe pathogenesis of autoimmune and
      some infectious diseases. It has been suggested that this is partially due to
      activation of plasmacytoid dendritic cells (pDCs), the main producers of
      interferon (IFN)-alpha, in response to toll-like receptor (TLR)7 stimulation. We
      investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation
      on isolated pDCs. Our data revealed a sex-specific differential expression of IFN
      Is, with pDCs from females showing a significantly higher mRNA expression of all
      13 IFN-alpha subtypes. In addition, pDCs from females had higher levels of IFN
      beta mRNA after stimulation, indicating that sex differences in IFN-I production
      by pDCs were mediated by a signaling event upstream of the first loop of IFN-I
      mRNA transcription. Furthermore, the surface expression levels of the common IFN
      alpha/beta receptor subunit 2 were significantly higher on pDCs from females in
      comparison to males. These data indicate that higher IFN-alpha production is
      already established at the mRNA level and propose a contribution of higher IFN
      alpha/beta receptor 2 expression on pDCs to the immunological differences in IFN
      I production observed between females and males.

PMID- 27891603
TI  - Using Harm-Based Weights for the AHRQ Patient Safety for Selected Indicators
      Composite (PSI-90): Does It Affect Assessment of Hospital Performance and
      Financial Penalties in Veterans Health Administration Hospitals?
AB  - OBJECTIVE: To assess whether hospital profiles for public reporting and pay-for
      performance, measured by the Agency for Healthcare Research and Quality (AHRQ)
      Patient Safety for Selected Indicators (PSI-90) composite measure, were affected
      by using the recently developed harm-based weights. DATA SOURCES/STUDY SETTING:
      Retrospective analysis of 2012-2014 data from the Veterans Health Administration
      (VA). STUDY DESIGN: The AHRQ PSI software (v5.0) was applied to obtain the
      original volume-based PSI-90 scores for 132 acute-care hospitals. We constructed
      a modified PSI-90 using the harm-based weights developed by AHRQ. We compared
      hospital profiles for public reporting and pay-for-performance between these two
      PSI-90s and assessed patterns in these changes. PRINCIPAL FINDINGS: The volume
      based and the harm-based PSI-90s were strongly correlated (r = 0.67, p < .0001).
      The use of the harm-based PSI-90 had a relatively small impact on public
      reporting (i.e., 5 percent hospitals changed categorization), but it had a much
      larger impact on pay-for-performance (e.g., 15 percent of hospitals would have
      faced different financial penalties under the Medicare Hospital-Acquired
      Condition Reduction Program). Because of changes in weights of specific PSIs,
      hospital profile changes occurred systematically. CONCLUSIONS: Use of the harm
      based weights in PSI-90 has the potential to significantly change payments under
      pay-for-performance programs. Policy makers should carefully develop transition
      plans for guiding hospitals through changes in any quality metrics used for pay
      for-performance.

PMID- 27891604
TI  - Best of the 2016 AcademyHealth Annual Research Meeting.

PMID- 27891606
TI  - Putting the 'point' back into the ritual: a binary approach to difficult airway
      prediction.

PMID- 27891602
TI  - Cannabimimetic phytochemicals in the diet - an evolutionary link to food
      selection and metabolic stress adaptation?
AB  - : The endocannabinoid system (ECS) is a major lipid signalling network that plays
      important pro-homeostatic (allostatic) roles not only in the nervous system but
      also in peripheral organs. There is increasing evidence that there is a dietary
      component in the modulation of the ECS. Cannabinoid receptors in hominids co
      evolved with diet, and the ECS constitutes a feedback loop for food selection and
      energy metabolism. Here, it is postulated that the mismatch of ancient lipid
      genes of hunter-gatherers and pastoralists with the high-carbohydrate diet
      introduced by agriculture could be compensated for via dietary modulation of the
      ECS. In addition to the fatty acid precursors of endocannabinoids, the potential
      role of dietary cannabimimetic phytochemicals in agriculturist nutrition is
      discussed. Dietary secondary metabolites from vegetables and spices able to
      enhance the activity of cannabinoid-type 2 (CB2 ) receptors may provide adaptive
      metabolic advantages and counteract inflammation. In contrast, chronic CB1
      receptor activation in hedonic obese individuals may enhance pathophysiological
      processes related to hyperlipidaemia, diabetes, hepatorenal inflammation and
      cardiometabolic risk. Food able to modulate the CB1 /CB2 receptor activation
      ratio may thus play a role in the nutrition transition of Western high-calorie
      diets. In this review, the interplay between diet and the ECS is highlighted from
      an evolutionary perspective. The emerging potential of cannabimimetic food as a
      nutraceutical strategy is critically discussed. LINKED ARTICLES: This article is
      part of a themed section on Principles of Pharmacological Research of
      Nutraceuticals. To view the other articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

PMID- 27891605
TI  - Are Two Heads Better Than One or Do Too Many Cooks Spoil the Broth? The Trade-Off
      between Physician Division of Labor and Patient Continuity of Care for Older
      Adults with Complex Chronic Conditions.
AB  - OBJECTIVE: To examine the effects of physician division of labor and patient
      continuity of care (COC) on the care quality and outcomes of older adults with
      complex chronic conditions. DATA SOURCES/STUDY SETTING: Seven years (2006-2012)
      of panel data from the Medicare Current Beneficiary Survey (MCBS). STUDY DESIGN:
      Regression models were used to estimate the effect of the specialty-type of
      physicians involved in annual patient evaluation and management, as well as
      patient COC, on simultaneous care processes and following year outcomes. DATA
      COLLECTION/EXTRACTION METHODS: Multiyear cohorts of Medicare beneficiaries with
      diabetes and/or heart failure were retrospectively identified to create a panel
      of 15,389 person-year observations. PRINCIPAL FINDINGS: Involvement of both
      primary care physicians and disease-relevant specialists is associated with
      better compliance with process-of-care guidelines, but patients seeing disease
      relevant specialists also receive more repeat cardiac imaging (p < .05). Patient
      COC is associated with less repeat cardiac imaging and compliance with some
      recommended care processes (p < .05), but the effects are small. Receiving care
      from a disease-relevant specialist is associated with lower rates of following
      year functional impairment, institutionalization in long-term care, and
      ambulatory care sensitive hospitalization (p < .05). CONCLUSIONS: Annual
      involvement of disease-relevant specialists in the care of beneficiaries with
      complex chronic conditions leads to more resource use but has a beneficial effect
      on outcomes.

PMID- 27891607
TI  - Cortical and reticular contributions to human precision and power grip.
AB  - KEY POINTS: The corticospinal tract contributes to the control of finger muscles
      during precision and power grip. We explored the neural mechanisms contributing
      to changes in corticospinal excitability during these gripping configurations.
      Motor evoked potentials (MEPs) elicited by cortical, but not by subcortical,
      stimulation were more suppressed during power grip compared with precision grip
      and index finger abduction. Intracortical inhibition was more reduced during
      power grip compared with the other tasks. An acoustic startle cue, a stimulus
      that engages the reticular system, suppressed MEP size during power grip to a
      lesser extent than during the other tasks at a cortical level and this positively
      correlated with changes in intracortical inhibition. Our findings suggest that
      changes in corticospinal excitability during gross more than fine finger
      manipulations are largely cortical in origin and that the reticular system
      contributed, at least in part, to these effects. ABSTRACT: It is well accepted
      that the corticospinal tract contributes to the control of finger muscles during
      precision and power grip in humans but the neural mechanisms involved remain
      poorly understood. Here, we examined motor evoked potentials elicited by cortical
      and subcortical stimulation of corticospinal axons (MEPs and CMEPs, respectively)
      and the activity in intracortical circuits (suppression of voluntary
      electromyography) and spinal motoneurons (F-waves) in an intrinsic hand muscle
      during index finger abduction, precision grip and power grip. We found that the
      size of MEPs, but not CMEPs, was more suppressed during power grip compared with
      precision grip and index finger abduction, suggesting a cortical origin for these
      effects. Notably, intracortical inhibition was more reduced during power grip
      compared with the other tasks. To further examine the origin of changes in
      intracortical inhibition we assessed the contribution of the reticular system,
      which projects to cortical neurons, and projects to spinal motoneurons
      controlling hand muscles. An acoustic startle cue, which engages the reticular
      system, suppressed MEP size during power grip to a lesser extent than during the
      other tasks and this positively correlated with changes in intracortical
      inhibition. A startle cue decreased intracortical inhibition, but not CMEPs,
      during power grip. F-waves remained unchanged across conditions. Our novel
      findings show that changes in corticospinal excitability present during power
      grip compared with fine finger manipulations are largely cortical in origin and
      suggest that the reticular system contributed, at least in part, to these
      effects.

PMID- 27891608
TI  - Compensatory axon sprouting for very slow axonal die-back in a transgenic model
      of spinal muscular atrophy type III.
AB  - KEY POINTS: Smn+/- transgenic mouse is a model of the mildest form of spinal
      muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old
      animals, muscular force is maintained. This maintained muscular force is mediated
      by reinnervation of the denervated fibres by surviving motoneurons. The spinal
      motoneurons in these animals do not show an increased susceptibility to death
      after nerve injury and they retain their regenerative capacity. We conclude that
      the hypothesized immaturity of the neuromuscular system in this model cannot
      explain the loss of motoneurons by systematic die-back. ABSTRACT: Spinal muscular
      atrophy (SMA) is a common autosomal recessive disorder in humans and is the
      leading genetic cause of infantile death. Patients lack the SMN1 gene with the
      severity of the disease depending on the number of copies of the highly
      homologous SMN2 gene. Although motoneuron death in the Smn+/- transgenic mouse
      model of the mildest form of SMA, SMA type III, has been reported, we have used
      retrograde tracing of sciatic and femoral motoneurons in the hindlimb with
      recording of muscle and motor unit isometric forces to count the number of
      motoneurons with intact neuromuscular connections. Thereby, we investigated
      whether incomplete maturation of the neuromuscular system induced by survival
      motoneuron protein (SMN) defects is responsible for die-back of axons relative to
      survival of motoneurons. First, a reduction of ~30% of backlabelled motoneurons
      began relatively late, at 11 months of age, with a significant loss of 19% at 7
      months. Motor axon die-back was affirmed by motor unit number estimation. Loss of
      functional motor units was fully compensated by axonal sprouting to retain normal
      contractile force in four hindlimb muscles (three fast-twitch and one slow
      twitch) innervated by branches of the sciatic nerve. Second, our evaluation of
      whether axotomy of motoneurons in the adult Smn+/- transgenic mouse increases
      their susceptibility to cell death demonstrated that all the motoneurons survived
      and they sustained their capacity to regenerate their nerve fibres. It is
      concluded the systematic die-back of motoneurons that innervate both fast- and
      slow-twitch muscle fibres is not related to immaturity of the neuromuscular
      system in SMA.

PMID- 27891609
TI  - Role of TRPM7 in cerebral ischaemia and hypoxia.
AB  - Transient receptor potential melastatin 7 (TRPM7) channel, a calcium-permeable
      non-selective divalent cation channel, is broadly expressed in various cells and
      tissues, including the brain. TRPM7 is thought to be coupled to the metabolic
      state and regulate calcium homeostasis in the cell. TRPM7 takes part in a wide
      range of cell biology processes that affect cell growth and proliferation, as
      well as in embryonic development and skeleton formation. TRPM7 plays a
      significant role in ischaemic and hypoxic brain injury and neuronal cell death.
      TRPM7, as a key non-glutamate mechanism of cerebral ischaemia, also triggers an
      intracellular ionic imbalance and neuronal cell death in ischaemia and hypoxia.
      We have reported that TRPM7 is expressed in neurons of the hippocampus and cortex
      and activation of TRPM7 induced ischaemic neuronal cell death; suppression of
      TRPM7 with virally mediated gene silencing using siRNA reduced ischaemic neuronal
      cell death and improved neurobehavioural outcomes in vivo. Recently, we also
      demonstrated that inhibition of TRPM7 using pharmacological means promoted
      neuronal outgrowth in vitro and provided neuroprotection against brain injury to
      hypoxia in vivo. Thus, we have shown the contributions of TRPM7 in many
      physiological and pathophysiological processes, including hypoxia and ischaemia.

PMID- 27891611
TI  - Pharmacokinetics cannot explain the increased effective dose requirement for
      morphine and midazolam in rats during their extended administration alone or in
      combination.
AB  - OBJECTIVES: Chronic administration of morphine and midazolam, alone or in
      combination, can induce tolerance to their effects. Data showed that co
      administration of morphine and midazolam increased effective dose requirement of
      morphine, exceeding that observed with morphine alone. METHODS: To elucidate the
      pharmacokinetic component to the tolerance, we administered midazolam (2 mg/kg)
      and morphine (10 mg/kg) alone or their combination daily to rats for 12 days
      followed by a pharmacokinetic study on day 13. On the study day, each animal
      received a single bolus dose of 5 mg/kg morphine, and 2 mg/kg of midazolam 30 s
      later. Multiple blood samples were obtained for 6 h. Plasma drug concentrations
      were assayed by mass spectrometry optimized for small samples. KEY FINDINGS: Mean
      morphine clearance was as follows: 22.2, 27.2, 26.0 and 23.4 l/h per kg in the
      saline-saline, saline-midazolam, saline-morphine and midazolam-morphine groups,
      respectively. Corresponding midazolam clearances were 32.8, 23.0, 22.2 and 31.1
      l/h per kg. ANOVA indicated no significant differences among the four groups in
      the clearances, half-lives, and volumes of distribution. Morphine and midazolam
      clearances were significantly correlated (R2 = 0.48, P < 0.001). CONCLUSIONS:
      This animal model suggests that altered pharmacokinetics cannot explain tolerance
      evidenced as increased dose requirement for morphine or midazolam, when
      administered alone or combination, for extended periods.

PMID- 27891610
TI  - Resveratrol supplementation of high-fat diet-fed pregnant mice promotes brown and
      beige adipocyte development and prevents obesity in male offspring.
AB  - KEY POINTS: Maternal high-fat diet impairs brown adipocyte function and
      correlates with obesity in offspring. Maternal resveratrol administration
      recovers metabolic activity of offspring brown adipose tissue. Maternal
      resveratrol promotes beige adipocyte development in offspring white adipose
      tissue. Maternal resveratrol intervention protects offspring against high-fat
      diet-induced obesity. ABSTRACT: Promoting beige/brite adipogenesis and
      thermogenic activity is considered as a promising therapeutic approach to reduce
      obesity and metabolic syndrome. Maternal obesity impairs offspring brown
      adipocyte function and correlates with obesity in offspring. We previously found
      that dietary resveratrol (RES) induces beige adipocyte formation in adult mice.
      Here, we evaluated further the effect of resveratrol supplementation of pregnant
      mice on offspring thermogenesis and energy expenditure. Female C57BL/6 J mice
      were fed a control diet (CON) or a high-fat diet (HFD) with or without 0.2% (w/w)
      RES during pregnancy and lactation. Male offspring were weaned onto a HFD and
      maintained on this diet for 11 weeks. The offspring thermogenesis and related
      regulatory factors in adipose tissue were evaluated. At weaning, HFD offspring
      had lower thermogenesis in brown and white adipose tissues compared with CON
      offspring, which was recovered by maternal RES supplementation, along with the
      appearance of multilocular brown/beige adipocytes and elevated thermogenic gene
      expression. Adult offspring of RES-treated mothers showed increased energy
      expenditure and insulin sensitivity when on an obesogenic diet compared with HFD
      offspring. The elevated metabolic activity was correlated with enhanced brown
      adipose function and white adipose tissue browning in HFD+RES compared with HFD
      offspring. In conclusion, RES supplementation of HFD-fed dams during pregnancy
      and lactation promoted white adipose browning and thermogenesis in offspring at
      weaning accompanied by persistent beneficial effects in protecting against HFD
      induced obesity and metabolic disorders.

PMID- 27891613
TI  - A Review of Spectroscopic and Biophysical-Chemical Studies of the Complex of
      Cyclobutane Pyrimidine Dimer Photolyase and Cryptochrome DASH with Substrate DNA.
AB  - Cyclobutane pyrimidine dimer (CPD) photolyase (PL) is a structure-specific DNA
      repair enzyme that uses blue light to repair CPD on DNA. Cryptochrome (CRY) DASH
      enzymes use blue light for the repair of CPD lesions on single-stranded (ss) DNA,
      although some may also repair these lesions on double-stranded (ds) DNA. In
      addition, CRY DASH may be involved in blue light signaling, similar to
      cryptochromes. The focus of this review is on spectroscopic and biophysical
      chemical experiments of the enzyme-substrate complex that have contributed to a
      more detailed understanding of all the aspects of the CPD repair mechanism of CPD
      photolyase and CRY DASH. This will be performed in the backdrop of the available
      X-ray crystal structures of these enzymes bound to a CPD-like lesion. These
      structures helped to confirm conclusions that were drawn earlier from
      spectroscopic and biophysical-chemical experiments, and they have a critical
      function as a framework to design new experiments and to interpret new
      experimental data. This review will show the important synergy between X-ray
      crystallography and spectroscopic/biophysical-chemical investigations that is
      essential to obtain a sufficiently detailed picture of the overall mechanism of
      CPD photolyases and CRY DASH proteins.

PMID- 27891614
TI  - ERECTA-family receptor kinase genes redundantly prevent premature progression of
      secondary growth in the Arabidopsis hypocotyl.
AB  - Secondary growth is driven by continuous cell proliferation and differentiation
      of the cambium that acts as vascular stem cells, producing xylem and phloem to
      expand vascular tissues laterally. During secondary growth of hypocotyls in
      Arabidopsis thaliana, the xylem undergoes a drastic phase transition from a
      parenchyma-producing phase to a fiber-producing phase at the appropriate time.
      However, it remains to be fully elucidated how progression of secondary growth is
      properly controlled. We focused on phenotypes of hypocotyl vasculatures caused by
      double mutation in ERECTA (ER) and ER-LIKE1 (ERL1) receptor-kinase genes to
      elucidate their roles in secondary growth. ER and ERL1 redundantly suppressed
      excessive radial growth of the hypocotyl vasculature during secondary growth. ER
      and ERL1 also prevented premature initiation of the fiber differentiation process
      mediated by the NAC SECONDARY WALL THICKENING PROMOTING FACTORs in the hypocotyl
      xylem. Upon floral transition, the hypocotyl xylem gained a competency to respond
      to GA in a BREVIPEDICELLUS-dependent manner, which was a prerequisite for fiber
      differentiation. However, even after the floral transition, ER and ERL1 prevented
      precocious initiation of the GA-mediated fiber formation. Collectively, our
      findings reveal that ER and ERL1 redundantly prevent premature progression of
      sequential events in secondary growth.

PMID- 27891612
TI  - Neurovascular mechanisms underlying augmented cold-induced reflex cutaneous
      vasoconstriction in human hypertension.
AB  - KEY POINTS: In hypertensive adults (HTN), cardiovascular risk increases
      disproportionately during environmental cold exposure. Despite ample evidence of
      dysregulated sympathetic control of the peripheral vasculature in hypertension,
      no studies have examined integrated neurovascular function during cold stress in
      HTN. The findings of the present study show that whole-body cold stress elicits
      greater increases in sympathetic outflow directed to the cutaneous vasculature
      and, correspondingly, greater reductions in skin blood flow in HTN. We further
      demonstrate an important role for non-adrenergic sympathetic co-transmitters in
      mediating the vasoconstrictor response to cold stress in hypertension. In the
      context of thermoregulation and the maintenance of core temperature,
      sympathetically-mediated control of the cutaneous vasculature is not only
      preserved, but also exaggerated in hypertension. Given the increasing prevalence
      of hypertension, clarifying the mechanistic underpinnings of hypertension-induced
      alterations in neurovascular function during cold exposure is clinically
      relevant. ABSTRACT: Despite ample evidence of dysregulated sympathetic control of
      the peripheral vasculature in hypertension, no studies have examined integrated
      neurovascular function during cold stress in hypertensive adults (HTN). We
      hypothesized that (i) whole-body cooling would elicit greater cutaneous
      vasoconstriction and greater increases in skin sympathetic nervous system
      activity (SSNA) in HTN (n = 14; 56 +/- 2 years) compared to age-matched
      normotensive adults (NTN; n = 14; 55 +/- 2 years) and (ii) augmented reflex
      vasoconstriction in HTN would be mediated by an increase in cutaneous vascular
      adrenergic sensitivity and a greater contribution of non-adrenergic sympathetic
      co-transmitters. SSNA (peroneal microneurography) and red cell flux (laser
      Doppler flowmetry; dorsum of foot) were measured during whole-body cooling (water
      perfused suit). Sympathetic adrenergic- and non-adrenergic-dependent
      contributions to reflex cutaneous vasoconstriction and vascular adrenergic
      sensitivity were assessed pharmacologically using intradermal microdialysis.
      Cooling elicited greater increases in SSNA (NTN: +64 +/- 13%baseline  vs. HTN:
      +194 +/- 26%baseline ; P < 0.01) and greater reductions in skin blood flow (NTN: 
      16 +/- 2%baseline  vs. HTN: -28 +/- 3%baseline ; P < 0.01) in HTN compared to
      NTN, reflecting an increased response range for sympathetic reflex control of
      cutaneous vasoconstriction in HTN. Norepinephrine dose-response curves showed no
      HTN-related difference in cutaneous adrenergic sensitivity (logEC50 ; NTN: -7.4
      +/- 0.3 log M vs. HTN: -7.5 +/- 0.3 log M; P = 0.84); however, non-adrenergic
      sympathetic co-transmitters mediated a significant portion of the vasoconstrictor
      response to cold stress in HTN. Collectively, these findings indicate that
      hypertension increases the peripheral cutaneous vasoconstrictor response to cold
      via greater increases in skin sympathetic outflow coupled with an increased
      reliance on non-adrenergic neurotransmitters.

PMID- 27891615
TI  - A large potentiation effect of serum on the in vitro potency of tulathromycin
      against Mannheimia haemolytica and Pasteurella multocida.
AB  - The antimicrobial properties of tulathromycin were investigated for M.
      haemolytica and P. multocida. Three in vitro indices of antimicrobial activity,
      minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC)
      and time-kill curves, were established for six isolates of each organism. Each
      index was measured in two growth media: Mueller-Hinton broth (MHB) and calf
      serum. It was shown that MICs and MBCs were markedly lower in serum than in MHB.
      MHB:serum ratios for MIC were 47:1 (M. haemolytica) and 53:1 (P. multocida). For
      both serum and MHB, adjustment of pH led to greater potency at alkaline compared
      to acid pH. Tulathromycin MIC was influenced by size of inoculum count, being 4.0
      to 7.7-fold greater for high compared to low initial counts. It was concluded
      that for the purpose of determining dosages for therapeutic use, pharmacodynamic
      data for tulathromycin should be derived in biological fluids such as serum. It
      is hypothesized that in vitro measurement of MIC in broth, conducted according to
      internationally recommended standards, may be misleading as a basis for
      estimating the in vivo potency of tulathromycin.

PMID- 27891616
TI  - Human papillomavirus-induced oropharyngeal cancer in Hispanics in the United
      States.
AB  - OBJECTIVES/HYPOTHESIS: Determine disparities in survival outcome and clinical
      presentation between Hispanic and non-Hispanic white patients with human
      papillomavirus-positive oropharyngeal squamous cell carcinoma. STUDY DESIGN:
      Retrospective clinical research. METHODS: Clinical data on Hispanics and non
      Hispanic white patients with diagnosis of human papillomavirus/p16-positive
      oropharyngeal squamous cell carcinoma were drawn from a tumor registry from the
      University of Miami Hospitals and Clinics from 2008 to 2014. Of 436 patients with
      oropharyngeal squamous cell carcinoma, 237 patents met inclusion criteria.
      Patient's age, gender, smoking history, alcohol history, race/ethnicity, tumor T
      stage, nodal N stage, and composite TNM stage were included in the analysis.
      Associations between race and other categorical variables were explored with chi2
      test or Fisher exact test where appropriate. Survival curves were generated using
      the Kaplan-Meier method. RESULTS: Significant differences in clinical
      presentation was detected between Hispanic (N = 70) and non-Hispanic white (N =
      167) patients. Hispanic human papillomavirus-positive oropharyngeal squamous cell
      carcinoma patients showed a higher proportion of women with disease, a higher
      proportion of patients presenting with tonsil rather than tongue base primary
      subsite cancer, and a higher proportion of patients who do not consume alcohol
      compared to non-Hispanic white human papillomavirus-positive oropharyngeal
      squamous cell carcinoma patients. A statistically significant survival difference
      between these two ethnic groups was not detected in the current dataset.
      CONCLUSIONS: Unique differences in clinical presentations between Hispanic
      patients and non-Hispanic whites with human papillomavirus-positive oropharyngeal
      squamous cell carcinoma were detected. This may be the first study to report
      novel clinical presentation in Hispanic human papillomavirus-positive patients
      with oropharyngeal squamous cell carcinoma living in the United States. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 127:1097-1101, 2017.

PMID- 27891617
TI  - Signet ring cell carcinoma of resectable metastatic colorectal cancer has rare
      surgical value.
AB  - BACKGROUND AND OBJECTIVES: Signet ring cell carcinoma (SRCC) is a uniquely
      separated subgroup in metastatic colorectal cancer (mCRC). The aims are to
      investigate the value of resection in patients with resectable metastatic signet
      ring cell colorectal cancer. METHODS: Patients with mCRC who underwent resection
      in Surveillance, Epidemiology, and End Results database during 1998-2010 were
      retrospectively analyzed. Kaplan-Meier and COX models were used to analyze the
      differences in the survival. Logistic regression models were used to evaluate the
      relationship between SRCC and other clinicopathological factors. RESULTS: Among
      the 3,568 patients, 94 (2.63%) patients had SRCC. The median survival time of
      patients with SRCC and non-SRCC were 17 and 29 months, respectively (P < 0.001).
      Multivariate analysis indicated that SRCC was an independent prognostic factor
      for poor overall survival. Logistic regression model based on variables
      identified by univariate analysis indicated that younger age (<=50 years old) (P
      = 0.005), female (P < 0.001), location in colon (P = 0.012), and N positive
      status (P = 0.003) were independent variables correlated with the SRCC subgroup.
      SRCC had a dramatically higher invalid surgical outcome rate than non-SRCC (P =
      0.001). CONCLUSION: SRCC patients might benefit little from the resection of
      primary and metastatic lesions with a high rate of undergoing invalid operations.
      J. Surg. Oncol. 2016;114:1004-1008. (c) 2016 Wiley Periodicals, Inc.

PMID- 27891619
TI  - The role of nutrients in drought-induced tree mortality and recovery.
AB  - Contents 513 I. 513 II. 514 III. 517 518 References 518 SUMMARY: Global forests
      are experiencing rising temperatures and more severe droughts, with consistently
      dire forecasts for negative future impacts. Current research on the physiological
      mechanisms underlying drought impacts is focused on the water- and carbon
      associated mechanisms. The role of nutrients is notably missing from this
      research agenda. Here, we investigate what role, if any, forest nutrition plays
      for survival and recovery of forests during and after drought. High nutrient
      availability may play a detrimental role in drought survival due to preferential
      biomass allocation aboveground that (1) predispose plants to hydraulic
      constraints limiting photosynthesis and promoting hydraulic failure, (2)
      increases carbon costs during periods of carbon starvation, and (3) promote
      biotic attack due to low tissue carbon: nitrogen (C : N). When nutrient uptake
      occurs during drought, high nutrient availability can increase water use
      efficiency thus minimizing negative feedbacks between carbon and nutrient
      balance. Nutrients are released after drought ceases, which might promote faster
      recovery but the temporal dynamics of microbial immobilization and nutrient
      leaching have a significant impact on nutrient availability. We provide a
      framework for understanding nutrient impacts on drought survival that allows a
      more complete analysis of forest ecosystem responses.

PMID- 27891618
TI  - CO2 studies remain key to understanding a future world.
AB  - Contents 34 I. 34 II. 36 III. 37 IV. 37 V. 38 38 References 38 SUMMARY:
      Characterizing plant responses to past, present and future changes in atmospheric
      carbon dioxide concentration ([CO2 ]) is critical for understanding and
      predicting the consequences of global change over evolutionary and ecological
      timescales. Previous CO2 studies have provided great insights into the effects of
      rising [CO2 ] on leaf-level gas exchange, carbohydrate dynamics and plant growth.
      However, scaling CO2 effects across biological levels, especially in field
      settings, has proved challenging. Moreover, many questions remain about the
      fundamental molecular mechanisms driving plant responses to [CO2 ] and other
      global change factors. Here we discuss three examples of topics in which
      significant questions in CO2 research remain unresolved: (1) mechanisms of CO2
      effects on plant developmental transitions; (2) implications of rising [CO2 ] for
      integrated plant-water dynamics and drought tolerance; and (3) CO2 effects on
      symbiotic interactions and eco-evolutionary feedbacks. Addressing these and other
      key questions in CO2 research will require collaborations across scientific
      disciplines and new approaches that link molecular mechanisms to complex
      physiological and ecological interactions across spatiotemporal scales.

PMID- 27891620
TI  - Modulation of formalin-induced pain-related behaviour by clonidine and yohimbine
      in the Speke's hinged tortoise (Kiniskys spekii).
AB  - The study was designed to investigate the involvement of noradrenergic and
      serotonergic receptor systems in the modulation of formalin-induced pain-related
      behaviour in the Speke's hinged tortoise. Intradermal injection of 100 MUL of
      formalin at a dilution of 12.5% caused pain-related behaviour (hindlimb
      withdrawal) that lasted for a mean time of 19.28 min (monophasic response).
      Intrathecal administration of clonidine (alpha2 -adrenergic receptor agonist) and
      yohimbine (alpha2 -adrenergic receptor antagonist) at a dose of 40 MUg/kg and
      37.5 MUg/kg or 50 MUg/kg, respectively, caused a highly significant reduction in
      the duration of the formalin-induced pain-related behaviour. The effect of
      clonidine was reversed by intrathecal administration of yohimbine at a dose of
      26.7 MUg/kg. The effect of yohimbine at a dose of 50 MUg/kg was reversed by
      intrathecal injection of 20 MUg/kg of the serotonergic receptor antagonist
      methysergide maleate. When performing antagonistic reactions, the administration
      of the antagonist was followed immediately by that of the agonist. The study
      indicates that for experimental purposes, intrathecal route of drug
      administration through the atlanto-occipital joint is effective in tortoises. The
      data also suggest that testudines have noradrenergic and serotonergic systems
      that appear to play a role in the modulation of pain in this species.

PMID- 27891622
TI  - Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight
      week-old dogs.
AB  - The safety profile of afoxolaner (an isoxazoline molecule) when combined with
      milbemycin oxime (a macrocyclic lactone) was evaluated according to the
      regulatory requirements when administered six times orally in a soft chewable
      formulation at a dose of at least 1*, 3*, or 5* the maximum exposure dose in 8
      week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were
      enrolled and allocated randomly to one of four treatment groups. Three doses were
      administered at 28-day intervals (Days 0, 28, and 56), followed by three
      additional doses administered with 14-day intervals (Days 84, 98, and 112). The
      study ended on Day 126. Treatment groups were as follows: Group 1: untreated,
      sham-dosed control; Group 2: afoxolaner/milbemycin oxime chews administered at a
      dose of at least 5 and 1 mg/kg, respectively (1*); Group 3: afoxolaner/milbemycin
      oxime chews administered at a dose of at least 15 and 3 mg/kg, respectively (3);
      and Group 4: afoxolaner/milbemycin oxime chews administered at a dose of at least
      25 and 5 mg/kg, respectively (5*). All dogs were examined for general health
      twice a day beginning on Day -14. Physical examinations, and blood collections
      for clinical pathology analysis and afoxolaner and milbemycin oxime plasma
      concentrations, were performed throughout the study. No afoxolaner/milbemycin
      oxime treatment-related changes were observed in growth, physical variables,
      clinical pathology variables, or tissues examined histologically. No clinically
      relevant or statistically significant health abnormalities related to the
      administration of afoxolaner/milbemycin oxime were observed. No signs of
      macrocyclic lactone sensitivity were observed at any time during the study.
      Vomiting and diarrhea were observed sporadically across all groups including the
      controls. Based upon the results of this study, afoxolaner/milbemycin oxime soft
      chewables were shown to be safe when administered repeatedly at up to 5* the
      maximum exposure dose in dogs as young as 8 weeks of age.

PMID- 27891623
TI  - Community-Based Financing of Family Planning in Developing Countries: A
      Systematic Review.
AB  - In this systematic review, we gather evidence on community financing schemes and
      insurance programs for family planning in developing countries, and we assess the
      impact of these programs on primary outcomes related to contraceptive use. To
      identify and evaluate the research findings, we adopt a four-stage review process
      that employs a weight-of-evidence and risk-of-bias analytic approach. Out of
      19,138 references that were identified, only four studies were included in our
      final analysis, and only one study was determined to be of high quality. In the
      four studies, the evidence on the impact of community-based financing on family
      planning and fertility outcomes is inconclusive. These limited and mixed findings
      suggest that either: 1) more high-quality evidence on community-based financing
      for family planning is needed before any conclusions can be made; or 2) community
      based financing for family planning may, in fact, have little or no effect on
      family planning outcomes.

PMID- 27891624
TI  - Quarantine versus pathogen-reduced plasma-coagulation factor content and
      rotational thromboelastometry coagulation.
AB  - BACKGROUND: Different types of fresh-frozen plasma (FFP) exist, and the
      concentrations of plasma proteins vary between individuals and blood groups.
      Furthermore, processing may also influence the content. Quarantine-stored plasma
      (qFFP) and plasma that was pathogen-reduced using blood-safety (Intercept)
      technology (piFFP) were analyzed regarding procoagulant and anticoagulant
      hemostasis proteins, including endogenous thrombin (thrombin-generation)
      potential (ETP). MATERIALS AND METHODS: Thirty-five samples of each type of FFP
      were analyzed using only male Blood Group O donors. FFP units were stored frozen
      for comparable periods of time before plasma protein content was assessed. Once
      the units were thawed, all tests were completed within 4 hours. The results are
      presented as means +/- standard deviations or as median (minimum; maximum) and
      were compared using independent-sample t tests (significance, p < 0.01). RESULTS:
      Significantly higher concentrations of adintegrin-like and metalloprotease with
      thrombospondin type-13 motifs (ADAMTS13), fibrinogen, Factor (F)V, FVIII, FXIII,
      protein S, protein S activity, antithrombin, microvesicle (<900 nm), and alpha2
      antiplasmin were observed in qFFP. The variability of factors was significantly
      lower in piFFP. Tissue factor (TF) at 1 picomolar (pM) exhibited significantly
      longer lag time, a lower peak, lower ETP, and a lower velocity index in qFFP
      compared with piFFP. In TF at 5 pM, significant differences in lag time (longer
      in qFFP), velocity index (lower in qFFP), and peak (lower in qFFP) were observed.
      Rotational thromboelastometry revealed a significantly longer (p = 0.002) clot
      formation time with intrinsic thromboelastometry for piFFP and a significantly
      shorter clotting time (p = 0.004) with thromboelastometry fibrinogen testing for
      piFFP. CONCLUSION: Pathogen reduction reduces procoagulant and anticoagulant
      coagulation factors as well as variability. A thrombin-generation assay showed no
      reduced ETP and no supraphysiological thrombin generation. None of the FFP
      preparations is likely to be effective for treating fibrinogen deficiency.

PMID- 27891621
TI  - Animal Cryptochromes: Divergent Roles in Light Perception, Circadian Timekeeping
      and Beyond.
AB  - Cryptochromes are evolutionarily related to the light-dependent DNA repair enzyme
      photolyase, serving as major regulators of circadian rhythms in insects and
      vertebrate animals. There are two types of cryptochromes in the animal kingdom:
      Drosophila-like CRYs that act as nonvisual photopigments linking circadian
      rhythms to the environmental light/dark cycle, and vertebrate-like CRYs that do
      not appear to sense light directly, but control the generation of circadian
      rhythms by acting as transcriptional repressors. Some animals have both types of
      CRYs, while others possess only one. Cryptochromes have two domains, the
      photolyase homology region (PHR) and an extended, intrinsically disordered C
      terminus. While all animal CRYs share a high degree of sequence and structural
      homology in their PHR domains, the C-termini are divergent in both length and
      sequence identity. Recently, cryptochrome function has been shown to extend
      beyond its pivotal role in circadian clocks, participating in regulation of the
      DNA damage response, cancer progression and glucocorticoid signaling, as well as
      being implicated as possible magnetoreceptors. In this review, we provide a
      historical perspective on the discovery of animal cryptochromes, examine
      similarities and differences of the two types of animal cryptochromes and explore
      some of the divergent roles for this class of proteins.

PMID- 27891625
TI  - Validation of the multiplex ligation-dependent probe amplification assay and its
      application on the distribution study of the major alleles of 17 blood group
      systems in Chinese donors from Guangzhou.
AB  - BACKGROUND: Genotyping platforms for common red blood cell (RBC) antigens have
      been successfully applied in Caucasian and black populations but not in Chinese
      populations. In this study, a genotyping assay based on multiplex ligation
      dependent probe amplification (MLPA) technology was applied in a Chinese
      population to validate the MLPA probes. Subsequently, the comprehensive
      distribution of 17 blood group systems also was obtained. STUDY DESIGN AND
      METHODS: DNA samples from 200 Chinese donors were extracted and genotyped using
      the blood-MLPA assay. To confirm the MLPA results, a second independent
      genotyping assay (ID Core+) was conducted in 40 donors, and serological typing of
      14 blood-group antigens was performed in 91 donors. In donors who had abnormal
      copy numbers of an allele (DI and GYPB) determined by MLPA, additional
      experiments were performed (polymerase chain reaction, sequencing, and flow
      cytometry analysis). RESULTS: The genotyping results obtained using the blood
      MLPA and ID Core+ assays were consistent. Serological data were consistent with
      the genotyping results except for one donor who had a Lu(a-b-) phenotype. Of the
      17 blood group systems, the distribution of the MNS, Duffy, Kidd, Diego, Yt, and
      Dombrock systems was polymorphic. The Mur and Sta antigens of the MNS system were
      distributed with a frequency of 9% (18 of 200) and 2% (4 of 200), respectively.
      One donor with chimerism and one who carried a novel DI*02(A845V) allele, which
      predicts the depression of Dib antigen expression, were identified. CONCLUSIONS:
      The blood-MLPA assay could easily identify the common blood-group alleles and
      correctly predicted phenotype in the Chinese population. The Mur and Sta antigens
      were distributed with high frequency in a Southern Chinese Han population.

PMID- 27891627
TI  - Narrative collisions, sociocultural pressures and dementia: the relational basis
      of personhood reconsidered.
AB  - The concept of personhood developed by Tom Kitwood highlights that the experience
      of dementia has relational dimensions that transcend the neurodegenerative
      impacts of the condition. This relational focus, however, has been narrowly
      conceptualised, with the impact of broader sociocultural factors on experience
      underplayed. The empirical exploration of interaction also requires
      reinforcement: a tendency for dyadic studies to portray findings in an
      individualised format hinders the interrogation of interpersonal negotiations.
      This article draws upon qualitative research that employed a joint interview
      approach, interviewing men with dementia and their spousal carers together. The
      focus on a dyadic case study from this research enables methodical exploration of
      the experience of living with dementia. This is realised by considering the
      socially-framed perspective of each person, and then how their perspectives are
      interwoven within interactional exchanges. This provides a platform for the
      evaluation of the current decontextualised notion of personhood and its
      implications. It is concluded that a sociologically-informed perspective can help
      to reinforce the academic understanding of personhood.

PMID- 27891626
TI  - Does trans-spinal and local DC polarization affect presynaptic inhibition and
      post-activation depression?
AB  - KEY POINTS: Trans-spinal polarization was recently introduced as a means to
      improve deficient spinal functions. However, only a few attempts have been made
      to examine the mechanisms underlying DC actions. We have now examined the effects
      of DC on two spinal modulatory systems, presynaptic inhibition and post
      activation depression, considering whether they might weaken exaggerated spinal
      reflexes and enhance excessively weakened ones. Direct current effects were
      evoked by using local intraspinal DC application (0.3-0.4 MUA) in deeply
      anaesthetized rats and were compared with the effects of trans-spinal
      polarization (0.8-1.0 mA). Effects of local intraspinal DC were found to be
      polarity dependent, as locally applied cathodal polarization enhanced presynaptic
      inhibition and post-activation depression, whereas anodal polarization weakened
      them. In contrast, both cathodal and anodal trans-spinal polarization facilitated
      them. The results suggest some common DC-sensitive mechanisms of presynaptic
      inhibition and post-activation depression, because both were facilitated or
      depressed by DC in parallel. ABSTRACT: Direct current (DC) polarization has been
      demonstrated to alleviate the effects of various deficits in the operation of the
      central nervous system. However, the effects of trans-spinal DC stimulation
      (tsDCS) have been investigated less extensively than the effects of transcranial
      DC stimulation, and their cellular mechanisms have not been elucidated. The main
      objectives of this study were, therefore, to extend our previous analysis of DC
      effects on the excitability of primary afferents and synaptic transmission by
      examining the effects of DC on two spinal modulatory feedback systems,
      presynaptic inhibition and post-activation depression, in an anaesthetized rat
      preparation. Other objectives were to compare the effects of locally and trans
      spinally applied DC (locDC and tsDCS). Local polarization at the sites of
      terminal branching of afferent fibres was found to induce polarity-dependent
      actions on presynaptic inhibition and post-activation depression, as cathodal
      locDC enhanced them and anodal locDC depressed them. In contrast, tsDCS modulated
      presynaptic inhibition and post-activation depression in a polarity-independent
      fashion because both cathodal and anodal tsDCS facilitated them. The results show
      that the local presynaptic actions of DC might counteract both excessively strong
      and excessively weak monosynaptic actions of group Ia and cutaneous afferents.
      However, they indicate that trans-spinally applied DC might counteract the
      exaggerated spinal reflexes but have an adverse effect on pathologically weakened
      spinal activity by additional presynaptic weakening. The results are also
      relevant for the analysis of the basic properties of presynaptic inhibition and
      post-activation depression because they indicate that some common DC-sensitive
      mechanisms contribute to them.

PMID- 27891628
TI  - Power, empowerment, and person-centred care: using ethnography to examine the
      everyday practice of unregistered dementia care staff.
AB  - The social positioning and treatment of persons with dementia reflects dominant
      biomedical discourses of progressive and inevitable loss of insight, capacity,
      and personality. Proponents of person-centred care, by contrast, suggest that
      such loss can be mitigated within environments that preserve rather than
      undermine personhood. In formal organisational settings, person-centred
      approaches place particular responsibility on 'empowered' direct-care staff to
      translate these principles into practice. These staff provide the majority of
      hands-on care, but with limited training, recognition, or remuneration. Working
      within a Foucauldian understanding of power, this paper examines the complex ways
      that dementia care staff engage with their own 'dis/empowerment' in everyday
      practice. The findings, which are drawn from ethnographic studies of three
      National Health Service (NHS) wards and one private care home in England, are
      presented as a narrative exploration of carers' general experience of
      powerlessness, their inversion of this marginalised subject positioning, and the
      related possibilities for action. The paper concludes with a discussion of how
      Foucault's understanding of power may help define and enhance efforts to empower
      direct-care staff to provide person-centred care in formal dementia care
      settings.

PMID- 27891629
TI  - Capping carious exposures in adults: a randomized controlled trial investigating
      mineral trioxide aggregate versus calcium hydroxide.
AB  - AIM: The aim of this multicentre, parallel-group randomized clinical trial was to
      compare the effectiveness of mineral trioxide aggregate (MTA) and a conventional
      calcium hydroxide liner (CH) as direct pulp capping materials in adult molars
      with carious pulpal exposure. METHODOLOGY: Seventy adults aged 18-55 years were
      randomly allocated to two parallel arms: MTA (White ProRoot, Dentsply, Tulsa
      Dental, Tulsa, OK, USA; n = 33) and CH (Dycal(r) , Dentsply DeTrey GmbH,
      Konstanz, Germany; n = 37). The teeth were temporized for 1 week with glass
      ionomer (Fuji IX, GC Corp, Tokyo, Japan) and then permanently restored with a
      composite resin. The subjects were followed up after 1 week and at six, 12, 24
      and 36 months. The primary outcome was the survival of the capped pulps, and the
      secondary outcome was postoperative pain after 1 week. Survival was defined as a
      nonsymptomatic tooth that responded to sensibility testing and did not exhibit
      periapical changes on radiograph. At each check-up, the pulp was tested for
      sensibility and a periapical radiograph was taken (excluding the radiographs
      taken at the 1-week follow-up). Kaplan-Meier survival analysis and log-rank test
      were used to assess the significant difference in the survival curves between
      groups. Chi-square test was used to assess the association between the materials
      and preoperative and postoperative pain. RESULTS: At 36 months, the Kaplan-Meier
      survival analysis showed a cumulative estimate rate of 85% for the MTA group and
      52% for the CH group (P = 0.006). There was no significant association between
      the capping material and postoperative pain. CONCLUSIONS: Mineral trioxide
      aggregate performed more effectively than a conventional CH liner as a direct
      pulp capping material in molars with carious pulpal exposure in adult patients.
      This study has been registered at ClinicalTrials.gov, number NCT01224925.

PMID- 27891630
TI  - Making Dissertations Publishable.

PMID- 27891631
TI  - Tutorial on statistical considerations on subgroup analysis in confirmatory
      clinical trials.
AB  - Clinical trials target patients who are expected to benefit from a new treatment
      under investigation. However, the magnitude of the treatment benefit, if it
      exists, often depends on the patient baseline characteristics. It is therefore
      important to investigate the consistency of the treatment effect across subgroups
      to ensure a proper interpretation of positive study findings in the overall
      population. Such assessments can provide guidance on how the treatment should be
      used. However, great care has to be taken when interpreting consistency results.
      An observed heterogeneity in treatment effect across subgroups can arise because
      of chance alone, whereas true heterogeneity may be difficult to detect by
      standard statistical tests because of their low power. This tutorial considers
      issues related to subgroup analyses and their impact on the interpretation of
      findings of completed trials that met their main objectives. In addition, we
      provide guidance on the design and analysis of clinical trials that account for
      the expected heterogeneity of treatment effects across subgroups by establishing
      treatment benefit in a pre-defined targeted subgroup and/or the overall
      population. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27891632
TI  - Randomised clinical trial: efficacy and safety of vonoprazan vs. lansoprazole in
      patients with gastric or duodenal ulcers - results from two phase 3, non
      inferiority randomised controlled trials.
AB  - BACKGROUND: Vonoprazan is a new potassium-competitive acid blocker for treatment
      of acid-related diseases. AIM: To conduct two randomised-controlled trials, to
      evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump
      inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU). METHODS:
      Patients aged >=20 years with >=1 endoscopically-confirmed GU or DU (>=5 mm white
      coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole
      (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary
      endpoint was the proportion of patients with endoscopically confirmed healed GU
      or DU. RESULTS: For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8%
      (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of
      vonoprazan to lansoprazole was confirmed [difference = -0.3% (95% CI -4.750,
      4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and
      98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non
      inferiority to lansoprazole was not confirmed [difference = -2.8% (95% CI -6.400,
      0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were
      slightly lower for GU and slightly higher for DU with vonoprazan than with
      lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan
      group (DU). The possibility of a relationship between this unexpected patient
      death and the study drug could not be ruled out. In both studies, increases in
      serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated
      patients; levels returned to baseline after treatment in both groups.
      CONCLUSIONS: Vonoprazan 20 mg has a similar tolerability profile to lansoprazole
      30 mg and is non-inferior with respect to GU healing and has similar efficacy for
      DU healing.

PMID- 27891633
TI  - Direct inhibition of Re Du Ning Injection and its active compounds on human liver
      cytochrome P450 enzymes by a cocktail method.
AB  - The aim of this study was to investigate the direct inhibitory effects of Re Du
      Ning Injection (RDN) and its active compounds on the major cytochrome P450 enzyme
      (CYP) isoforms (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) of
      human liver microsomes by 'a cocktail method'. The activity of each CYP isform
      was represented as the formation rate of the specific metabolite from relevant
      substrate. Then a sensitive and specific ultra-performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to
      simultaneously analyze the seven metabolites. RDN (0.035-2.26 mg/mL) showed a
      strong inhibitiory effect on CYP2C8, followed by CYP2C9, CYP2B6, CYP2C19, CYP1A2
      and CYP3A4. The IC50 value for each enzyme was 0.19, 0.66, 0.72, 1.27, 1.66 and
      2.13 mg/mL, respectively. RDN competitively inhibited the activities of CYP1A2
      (Ki  = 1.22 mg/mL), CYP2B6 (Ki  = 0.65 mg/mL) and CYP3A4 (Ki  = 0.88 mg/mL); it
      also exhibited mixed inhibition of CYP2C8, CYP2C9 and CYP2C19 with a Ki value of
      0.26, 0.64 and 0.82 mg/mL, respectively. However, the activity of CYP2D6 was not
      significantly inhibited even by 2.26 mg/mL RDN. Moreover, the data of nine active
      compounds on the CYPs showed that cryptochlorogenin acid, sochlorogenic acid B
      and sochlorogenic acid C were the major contributors to the inhibitory effect of
      RDN on CYP2C8, while the inhibitory effect of RDN on CYP2C9 might be caused by
      sochlorogenic acid A and sochlorogenic acid C. Moreover, neochlorogenic acid
      might be the major contributor to the inhibitory effect on CYP2B6. All of the
      findings suggested that drug-drug interactions may occur and great caution should
      be taken when RDN is combined with drugs metabolized by these CYPs.

PMID- 27891634
TI  - Sensitive determination of sulfonamides in environmental water by capillary
      electrophoresis coupled with both silvering detection window and in-capillary
      optical fiber light-emitting diode-induced fluorescence detector.
AB  - A new detector, silvering detection window and in-capillary optical fiber light
      emitting diode-induced fluorescence detector (SDW-ICOF-LED-IFD), is introduced
      for capillary electrophoresis (CE). The strategy of the work was that half
      surface of the detection window was coated with silver mirror, which could
      reflect the undetected fluorescence to the photomultiplier tube to be detected,
      consequently enhancing the detection sensitivity. Sulfonamides (SAs) are
      important antibiotics that achieved great applications in many fields. However,
      they pose a serious threat on the environment and human health when they enter
      into the environment. The SDW-ICOF-LED-IFD-CE system was used to determine
      fluorescein isothiocyanate (FITC)-labeled sulfadoxine (SDM), sulfaguanidine (SGD)
      and sulfamonomethoxine sodium (SMM-Na) in environmental water. The detection
      results obtained by the SDW-ICOF-LED-IFD-CE system were compared to those
      acquired by the CE with in-capillary optical fiber light-emitting diode-induced
      fluorescence detection (ICOF-LED-IFD-CE). The limits of detection (LODs) of SDW
      ICOF-LED-IFD-CE and ICOF-LED-IFD-CE were 1.0-2.0 nM and 2.5-7.7 nM (S/N = 3),
      respectively. The intraday (n = 6) and interday (n = 6) precision of migration
      time and corresponding peak area for both types of CE were all less than 0.86%
      and 3.68%, respectively. The accuracy of the proposed method was judged by
      employing standard addition method, and recoveries obtained were in the range of
      92.5-102.9%. The results indicated that the sensitivity of the SDW-ICOF-LED-IFD
      CE system was improved, and that its reproducibility and accuracy were
      satisfactory. It was successfully applied to analyze SAs in environmental water.

PMID- 27891635
TI  - Potential Association between Drug Shortages and High-Cost Medications.
AB  - Shortages and sudden price increases of certain drugs may both occur emergently,
      with little to no warning, and they can have a dramatic impact on patient care.
      Little data are available linking drug shortages and price increases. Many of the
      same characteristics that may make medications susceptible to shortages can also
      place them at risk for sudden price increases. These characteristics include
      unapproved drugs, off-patent sole-source medications, and infrequently used
      medications. We reviewed drug shortage data from the University of Utah Drug
      Information Service to demonstrate how frequently these characteristics occurred
      and resulted in higher drug prices. Clinicians can use drug shortage management
      principles to mitigate the impact of sudden price increases for patients and
      health care organizations.

PMID- 27891636
TI  - Effects of pulsed-radiofrequency neuromodulation on the rat with overactive
      bladder.
AB  - AIM: To quantify the effects of pulsed radiofrequency (PRF) electrical
      stimulations of the pudendal and pelvic nerves on the bladder function of rats
      with detrusor overactivity. METHODS: All rats were pretreated with a continuous
      transvesical infusion of 0.5% acetic acid (AA) for inducing detrusor
      overactivity. Intravesical pressure was recorded using cysometrography (CMG)
      during the continuous transvesical infusion to examine the effects of PRF
      electrical stimulation of the pudendal and pelvic nerves individually. In
      addition, the activity of caspase-3, an apoptosis marker, in the pelvic nerve was
      examined to evaluate the impact of PRF on nerve injury. RESULTS: According to the
      first CMG recording, AA treatment significantly reduced bladder capacity (BC) and
      intercontraction interval (ICI) to 65% and 66% of the corresponding control
      values, respectively. Subsequently, PRF electrical stimulation of the pelvic
      nerve inhibited AA-induced detrusor overactivity and significantly increased BC
      to approximately 102-110% and ICI to 79-92%; these effects persisted for at least
      4 h. Furthermore, PRF did not cause significant neural damage to the target
      stimulated nerves, as demonstrated by caspase-3 activity. CONCLUSION: PRF
      electrical stimulation of pelvic nerves exerted a long-lasting effect of
      suppressing AA-induced detrusor overactivity. This modality can be used as an
      alternative approach for improving bladder continence in patients with overactive
      bladder syndrome.

PMID- 27891637
TI  - Fetal magnetocardiography using optically pumped magnetometers: a more adaptable
      and less expensive alternative?
AB  - Fetal magnetocardiography provides the requisite precision for diagnostic
      measurement of electrophysiological events in the fetal heart. Despite its
      significant benefits, this technique with current cryogenic based sensors has
      been limited to few centers, due to high cost of maintenance. In this study, we
      show that a less expensive non-cryogenic alternative, optically pumped
      magnetometers, can provide similar electrophysiological and quantitative
      characteristics when subjected to direct comparison with the current technology.
      Further research can potentially increase its clinical use for fetal
      magnetocardiography. (c) 2016 John Wiley & Sons, Ltd.

PMID- 27891638
TI  - Regenerative potential of leucocyte- and platelet-rich fibrin. Part B: sinus
      floor elevation, alveolar ridge preservation and implant therapy. A systematic
      review.
AB  - AIM: To analyse the effect of leucocyte- and platelet-rich fibrin (L-PRF) on bone
      regeneration procedures and osseointegration. MATERIALS AND METHODS: An
      electronic and hand search was conducted in three databases (MEDLINE, EMBASE and
      Cochrane). Only randomized clinical trials, written in English where L-PRF was
      applied in bone regeneration and implant procedures, were selected. No follow-up
      restrictions were applied. RESULTS: A total of 14 articles were included and
      processed. Three subgroups were created depending on the application: sinus floor
      elevation (SFE), alveolar ridge preservation and implant therapy. In SFE, for a
      lateral window as well as for the trans-alveolar technique, histologically faster
      bone healing was reported when L-PRF was added to most common xenografts. L-PRF
      alone improved the preservation of the alveolar width, resulting in less buccal
      bone resorption compared to natural healing. In implant therapy, better implant
      stability over time and less marginal bone loss were observed when L-PRF was
      applied. Meta-analyses could not be performed due to the heterogeneity of the
      data. CONCLUSIONS: Despite the lack of strong evidence found in this systematic
      review, L-PRF might have a positive effect on bone regeneration and
      osseointegration.

PMID- 27891640
TI  - Chasing the Dream: Message From the President.

PMID- 27891639
TI  - Consensus report: faecal microbiota transfer - clinical applications and
      procedures.
AB  - BACKGROUND: Faecal microbiota transplantation or transfer (FMT) aims at replacing
      or reinforcing the gut microbiota of a patient with the microbiota from a healthy
      donor. Not many controlled or randomised studies have been published evaluating
      the use of FMT for other diseases than Clostridium difficile infection, making it
      difficult for clinicians to decide on a suitable indication. AIM: To provide an
      expert consensus on current clinical indications, applications and methodological
      aspects of FMT. METHODS: Well-acknowledged experts from various countries in
      Europe have contributed to this article. After literature review, consensus has
      been achieved by repetitive circulation of the statements and the full manuscript
      among all authors with intermittent adaptation to comments (using a modified
      Delphi process). Levels of evidence and agreement were rated according to the
      GRADE system. Consensus was defined a priori as agreement by at least 75% of the
      authors. RESULTS: Key recommendations include the use of FMT in recurrent C.
      difficile infection characterised by at least two previous standard treatments
      without persistent cure, as well as its consideration in severe and severe
      complicated C. difficile infection as an alternative to total colectomy in case
      of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases
      (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be
      performed in research settings. CONCLUSIONS: Faecal microbiota transplantation or
      transfer is a promising treatment for a variety of diseases in which the
      intestinal microbiota is disturbed. For indications other than C. difficile
      infection, more evidence is needed before more concrete recommendations can be
      made.

PMID- 27891641
TI  - Corrigendum.

PMID- 27891642
TI  - Photosynthesis: ancient, essential, complex, diverse ... and in need of
      improvement in a changing world.

PMID- 27891643
TI  - Alistair M. Hetherington.

PMID- 27891644
TI  - Bark thickness and fire regime: another twist.

PMID- 27891645
TI  - Nicotiana benthamiana as a nonhost of Zymoseptoria tritici.

PMID- 27891646
TI  - Nitrogen transport in the orchid mycorrhizal symbiosis - further evidence for a
      mutualistic association.

PMID- 27891648
TI  - Ethics in scientific publishing.

PMID- 27891647
TI  - A roadmap for improving the representation of photosynthesis in Earth system
      models.
AB  - Accurate representation of photosynthesis in terrestrial biosphere models (TBMs)
      is essential for robust projections of global change. However, current
      representations vary markedly between TBMs, contributing uncertainty to
      projections of global carbon fluxes. Here we compared the representation of
      photosynthesis in seven TBMs by examining leaf and canopy level responses of
      photosynthetic CO2 assimilation (A) to key environmental variables: light,
      temperature, CO2 concentration, vapor pressure deficit and soil water content. We
      identified research areas where limited process knowledge prevents inclusion of
      physiological phenomena in current TBMs and research areas where data are
      urgently needed for model parameterization or evaluation. We provide a roadmap
      for new science needed to improve the representation of photosynthesis in the
      next generation of terrestrial biosphere and Earth system models.

PMID- 27891649
TI  - Control of Arabidopsis lateral root primordium boundaries by MYB36.
AB  - Root branching in plants relies on the de novo formation of lateral roots. These
      are initiated from founder cells, triggering new formative divisions that
      generate lateral root primordia (LRP). The LRP size and shape depends on the
      balance between positive and negative signals that control cell proliferation.
      The mechanisms controlling proliferation potential of LRP cells remains poorly
      understood. We found that Arabidopsis thaliana MYB36, which have been previously
      shown to regulate genes required for Casparian strip formation and the transition
      from proliferation to differentiation in the primary root, plays a new role in
      controlling LRP development at later stages. We found that MYB36 is a novel
      component of LR development at later stages. MYB36 was expressed in the cells
      surrounding LRP where it controls a set of peroxidase genes, which maintain
      reactive oxygen species (ROS) balance. This was required to define the transition
      between proliferating and arrested cells inside the LRP, coinciding with the
      change from flat to dome-shaped primordia. Reducing the levels of hydrogen
      peroxide (H2 O2 ) in myb36-5 significantly rescues the mutant phenotype. Our
      results uncover a role for MYB36 outside the endodermis during LRP development
      through a mechanism analogous to regulating the proliferation/differentiation
      transition in the root meristem.

PMID- 27891650
TI  - Estimating time-dependent ROC curves using data under prevalent sampling.
AB  - Prevalent sampling is frequently a convenient and economical sampling technique
      for the collection of time-to-event data and thus is commonly used in studies of
      the natural history of a disease. However, it is biased by design because it
      tends to recruit individuals with longer survival times. This paper considers
      estimation of time-dependent receiver operating characteristic curves when data
      are collected under prevalent sampling. To correct the sampling bias, we develop
      both nonparametric and semiparametric estimators using extended risk sets and the
      inverse probability weighting techniques. The proposed estimators are consistent
      and converge to Gaussian processes, while substantial bias may arise if standard
      estimators for right-censored data are used. To illustrate our method, we analyze
      data from an ovarian cancer study and estimate receiver operating characteristic
      curves that assess the accuracy of the composite markers in distinguishing
      subjects who died within 3-5 years from subjects who remained alive. Copyright
      (c) 2016 John Wiley & Sons, Ltd.

PMID- 27891652
TI  - A closed testing procedure to select an appropriate method for updating
      prediction models.
AB  - Prediction models fitted with logistic regression often show poor performance
      when applied in populations other than the development population. Model updating
      may improve predictions. Previously suggested methods vary in their extensiveness
      of updating the model. We aim to define a strategy in selecting an appropriate
      update method that considers the balance between the amount of evidence for
      updating in the new patient sample and the danger of overfitting. We consider
      recalibration in the large (re-estimation of model intercept); recalibration (re
      estimation of intercept and slope) and model revision (re-estimation of all
      coefficients) as update methods. We propose a closed testing procedure that
      allows the extensiveness of the updating to increase progressively from a minimum
      (the original model) to a maximum (a completely revised model). The procedure
      involves multiple testing with maintaining approximately the chosen type I error
      rate. We illustrate this approach with three clinical examples: patients with
      prostate cancer, traumatic brain injury and children presenting with fever. The
      need for updating the prostate cancer model was completely driven by a different
      model intercept in the update sample (adjustment: 2.58). Separate testing of
      model revision against the original model showed statistically significant
      results, but led to overfitting (calibration slope at internal validation =
      0.86). The closed testing procedure selected recalibration in the large as update
      method, without overfitting. The advantage of the closed testing procedure was
      confirmed by the other two examples. We conclude that the proposed closed testing
      procedure may be useful in selecting appropriate update methods for previously
      developed prediction models. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27891651
TI  - Developing a Bayesian adaptive design for a phase I clinical trial: a case study
      for a novel HIV treatment.
AB  - The design of phase I studies is often challenging, because of limited evidence
      to inform study protocols. Adaptive designs are now well established in cancer
      but much less so in other clinical areas. A phase I study to assess the safety,
      pharmacokinetic profile and antiretroviral efficacy of C34-PEG4 -Chol, a novel
      peptide fusion inhibitor for the treatment of HIV infection, has been set up with
      Medical Research Council funding. During the study workup, Bayesian adaptive
      designs based on the continual reassessment method were compared with a more
      standard rule-based design, with the aim of choosing a design that would maximise
      the scientific information gained from the study. The process of specifying and
      evaluating the design options was time consuming and required the active
      involvement of all members of the trial's protocol development team. However, the
      effort was worthwhile as the originally proposed rule-based design has been
      replaced by a more efficient Bayesian adaptive design. While the outcome to be
      modelled, design details and evaluation criteria are trial specific, the
      principles behind their selection are general. This case study illustrates the
      steps required to establish a design in a novel context. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27891653
TI  - Polymorphisms in cytokine genes influence cognitive and functional performance in
      a population aged 75 years and above.
AB  - OBJECTIVE: To investigate the frequency of the cytokine single nucleotide
      polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha -308G > A, tumor growth
      factor (TGF)-beta1 codon +10C > T, TGF-beta1 codon +25G > C, interleukin (IL)-10 
      1082A > G, IL-10 -819C > T, IL-10 -592C > A, IL-6 -174G > C, and IFN-gamma +874T
      > A in a sample of healthy and cognitively impaired elderlies and to verify the
      probable association between these SNPs and cognitive and functional performance
      of subjects aged 75 years and above. METHODS: 259 Brazilian subjects were
      included, comprising 81 with cognitive impairment no dementia (CIND) and 54
      demented seniors (together made up the cognitively impaired group, CI) and 124
      age-matched and gender-matched cognitively healthy controls (CHS). The genotyping
      was performed by multiplex polymerase chain reaction. The cognitive performance
      was evaluated by Mini-Mental State Examination Brief Cognitive Screening Battery.
      The functional performance was accessed by Functional Activities Questionnaire.
      RESULTS: The CClower genotype of TGF-beta1 codon +25G > C was frequent in both
      patient groups. The TThigher genotype of INF-gamma +874T > A was less frequent in
      the dementia group. IL-10 haplotypes of lower expression were more frequent among
      CIND and demented patients. In CI, individuals with genetic variants that produce
      higher expression of TGF-beta1, INF-gamma, and IL-10 showed better normalized
      cognitive performance. Additionally, the Alower allele of INF-gamma +874T > A was
      related to worse functional performance in CI, while the Alower allele of TNF
      alpha -308G > A was associated with better cognitive and functional scores in the
      CIND group. CONCLUSIONS: Our findings suggest a potential role for certain
      cytokine SNPs in the development of CIND and dementia, which may influence the
      functional and cognitive performance of these patients. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27891654
TI  - The relationship between oestrogen receptor-alpha phosphorylation and the tumour
      microenvironment in patients with primary operable ductal breast cancer.
AB  - AIMS: Although the role of phosphorylation of oestrogen receptor (ER) at serines
      118 (p-S118) and 167 (p-S167) has been studied, the relationship between p-S118,
      p-S167 and the tumour microenvironment in ER-positive primary operable ductal
      breast cancers have not been investigated. The aims of this study are to
      investigate (i) the relationship between p-S118/p-S167 and the tumour
      microenvironment, and (ii) the effect of p-S118/167 on survival and recurrence in
      ER-positive primary operable ductal breast cancers. METHODS AND RESULTS: Patients
      presenting at three Glasgow hospitals between 1995 and 1998 with invasive ductal
      ER-positive primary breast cancers were studied (n = 294). Immunohistochemical
      staining of p-S118 and p-S167 was performed and their association with
      clinicopathological characteristics, cancer-specific survival (CSS) and
      recurrence-free interval (RFI) were examined. In the whole cohort, tumour size (P
      < 0.05) and microvessel density (P < 0.05) were associated with high p-S118 while
      increased micovessel density (P < 0.05), apoptosis (P < 0.05), general
      inflammatory infiltrate measured using the Klintrup-Makinen score (P < 0.05) and
      macrophage infiltrate (P < 0.05) were found to be associated with high p-S167.
      Only high p-S167 was associated with shorter CSS (P < 0.005) and shorter RFI in
      the whole cohort (P = 0.001) and separately in the luminal A (P < 0.05) and B
      tumours (P < 0.05). CONCLUSIONS: This study showed that both p-S118 and p-S167
      were associated with several microenvironmental factors, including increased
      microvessel density. In particular, p-S167 was associated with reduced RFI and
      CSS in the whole cohort and RFI in luminal A and B tumours and could possibly be
      employed to predict response to kinase inhibitors.

PMID- 27891656
TI  - The early intervention message: perspectives of parents of children with autism
      spectrum disorder.
AB  - BACKGROUND: There is strong evidence that early intervention (EI) can improve
      outcomes for children with autism spectrum disorder (ASD), and consequently, the
      importance of EI has been widely promoted to families of children with ASD.
      However, the perspectives of parents of children with ASD regarding the EI
      message have not been widely examined. METHODS: This study used qualitative
      methods to explore parental perspectives on the EI message. Semi-structured
      interviews were undertaken with 14 participants from 12 family units to explore
      the perspectives of parents of children with ASD on the EI message. Thematic
      analysis was undertaken on the data. RESULTS: Three central themes were
      constructed following data analysis: (i) parents' initial perceptions of EI
      following their child's diagnosis with ASD; (ii) the consequences (both positive
      and negative) of the EI message; and (iii) parents' perspectives on life after
      EI. The results of this study indicated that parents were acutely aware of the
      importance of EI, and although this provided parents with hope immediately post
      diagnosis, it also placed pressure on parental decision-making regarding which
      intervention approaches to access for their children with ASD. CONCLUSIONS: The
      results of this study highlight the importance of carefully considering how
      health messages, specifically the importance of EI, are communicated to families
      of children with ASD. Furthermore, the findings of this study also highlight the
      need for allied health professionals to communicate openly with parents about the
      anticipated outcomes of EI programmes.

PMID- 27891655
TI  - A comparison of parent and childcare provider's attitudes and perceptions about
      preschoolers' physical activity and outdoor time.
AB  - BACKGROUND: Young children depend on adult caregivers to provide opportunities
      for physical activity. Research has focused on barriers and facilitators to
      children's physical activity while in childcare, but parental influences remain
      largely unknown. This study examines parent's attitudes about preschoolers'
      physical activity and outdoor time, compares them with those of childcare
      providers and determines the association between parental attitudes and
      preschoolers' measured activity. METHODS: Parents and childcare providers from 30
      childcare centres were surveyed regarding attitudes towards preschoolers'
      physical activity and outdoor time. Children's moderate-to-vigorous physical
      activity was determined by using 24-h accelerometry. Parent and childcare
      providers' responses were compared. Mixed-effect linear regression examined
      moderate-to-vigorous physical activity and sedentary time as outcomes with
      parental attitudes as predictors, family demographics as covariates and centre as
      a random effect. RESULTS: Three hundred eighty-eight parents and 151 childcare
      providers participated. On average, children were 4.3 (0.7) years old. Parents
      and childcare providers both considered daily physical activity important for
      preschoolers, but providers rated the importance of daily outdoor time higher on
      a 10-point scale (8.9 vs. 7.6, P < 0.001). More parents than providers believed
      that children would get sick by playing outside in the cold (25 vs. 11%, P <
      0.05). Parents were more comfortable with their child playing outside at
      childcare compared with outside at home (8.9 vs. 6.9, P < 0.001). Lower income
      parents felt less comfortable than higher income parents with their child playing
      outside either near home or at childcare. Neither home nor total child activity
      levels were associated with most parental attitudes queried. CONCLUSIONS: While
      parents and childcare providers value daily physical activity for children, some
      parents expressed discomfort about their young children engaging in outdoor play,
      especially around home and in cold weather. These findings highlight the
      importance of childcare-based interventions to promote preschoolers' physical
      activity and outdoor play.

PMID- 27891657
TI  - Sleep differences in one-year-old children were related to obesity risks based on
      their parents' weight according to baseline longitudinal study data.
AB  - AIM: Parental obesity is the predominant risk factor for child obesity. We
      compared sleep in one-year-old children with different obesity risks, based on
      parental weight, and explored associations with weight, parental sleep and family
      factors. METHODS: Baseline data from 167 families participating in a longitudinal
      obesity prevention programme was used. Sleep patterns were compared between
      groups with high and low obesity risks, based on parental weight, and
      associations between child sleep and weight status, family obesity risk and
      parental sleep were explored. Sleep was assessed using child sleep diaries and
      standard parental questionnaires. RESULTS: Later bedtime, longer sleep onset
      latency and lower sleep efficiency were observed among children in the high-risk
      group. Child sleep onset latency was associated with the family obesity risk
      (beta = 0.25, p = 0.001), child bedtime with both maternal (beta = 0.33, p <
      0.01) and paternal bedtime (beta = 0.22, p < 0.05) and child sleep efficiency
      with maternal sleep quality (beta = 0.20, p < 0.01). The child's bedtime was
      weakly associated with their body mass index (beta = 0.17, p < 0.05). CONCLUSION:
      Sleep differed between one-year-old children with high or low obesity risks,
      based on their parents' body mass index, and was associated with the family
      obesity risk and parental sleep. The child's bedtime was weakly associated with
      their weight status.

PMID- 27891659
TI  - ICS teaching module: Cystometry (basic module).
AB  - AIMS: To summarize the evidence background for education of good urodynamic
      practice, especially cystometry. METHODS: A search was done in PubMed for the
      last 5 years of publications selecting only clinical studies, utilizing the
      following keywords: cystometry 133 articles and filling cystometry 53 articles.
      RESULTS: The evidence with regard to clinical setting and cystometry technique,
      as well as for catheters and transducers type, infused solution and patient
      position is presented with recommendations. Also the practice of determining
      bladder filling sensation and capacity and the basis of detrusor storage function
      diagnosis is educated. CONCLUSIONS: This manuscript provides the evidence
      background for the practice of cystometry. Neurourol. Urodynam. 9999:XX-XX, 2016.
      (c) 2016 Wiley Periodicals, Inc.

PMID- 27891658
TI  - The Impact of Neighborhood Conditions and Psychological Distress on Preterm Birth
      in African-American Women.
AB  - OBJECTIVE: Prior research suggests that adverse neighborhood conditions are
      related to preterm birth. One potential pathway by which neighborhood conditions
      increase the risk for preterm birth is by increasing women's psychological
      distress. Our objective was to examine whether psychological distress mediated
      the relationship between neighborhood conditions and preterm birth. DESIGN AND
      SAMPLE: One hundred and one pregnant African-American women receiving prenatal
      care at a medical center in Chicago participated in this cross-sectional design
      study. MEASURES: Women completed the self-report instruments about their
      perceived neighborhood conditions and psychological distress between 15-26 weeks
      gestation. Objective measures of the neighborhood were derived using geographic
      information systems (GIS). Birth data were collected from medical records.
      RESULTS: Perceived adverse neighborhood conditions were related to psychological
      distress: perceived physical disorder (r = .26, p = .01), perceived social
      disorder (r = .21, p = .03), and perceived crime (r = .30, p = .01). Objective
      neighborhood conditions were not related to psychological distress. Psychological
      distress mediated the effects of perceived neighborhood conditions on preterm
      birth. CONCLUSIONS: Psychological distress in the second trimester mediated the
      effects of perceived, but not objective, neighborhood conditions on preterm
      birth. If these results are replicable in studies with larger sample sizes,
      intervention strategies could be implemented at the individual level to reduce
      psychological distress and improve women's ability to cope with adverse
      neighborhood conditions.

PMID- 27891660
TI  - Small bowel Epstein-Barr virus-positive lympho-epithelioma-like carcinoma in
      Crohn's disease.

PMID- 27891661
TI  - Synergistic effects of polydatin and vitamin C in inhibiting cardiotoxicity
      induced by doxorubicin in rats.
AB  - The purpose of this study was to assess the synergistic effect of polydatin and
      vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats.
      Polydatin could significantly increase the activity of superoxide dismutase (SOD)
      and the heart rate, attenuate myocardial pathological damage, decrease
      malondialdehyde (MDA) content, slightly increase arterial pressure and
      glutathione peroxidase (GSH-Px) activity, reduce intervals of QRS, QT, and ST,
      and lower free fatty acid (FFA) content. The combination of polydatin and vitamin
      C could significantly increase arterial pressure and heart rate, decrease QRS
      interval and slightly reduce ST and QT intervals, significantly attenuate
      myocardial pathological damage, increase the activities of GSH-Px,T-SOD, Na+ K+ 
      ATPase, and Ca2+ Mg2+ -ATPase, elevate phosphocreatine (PCr) and adenosine
      triphosphate (ATP) contents, slightly increase adenosine diphosphate (ADP) and
      total adenine nucleotide (TAN) contents and PCr/ATP, and significantly decrease
      the contents of MDA and FFA, when compared with those in the DOX group.
      Meanwhile, the improvement effects on FFA content, the activities of ATPase and
      SOD, and contents of ATP and TAN in combination group were more obvious than
      those in polydatin group, and the improvement effects on arterial pressure, heart
      rate, interval of QRS, GSH-Px activity, and MDA, ADP, and PCr contents in
      combination group were slightly obvious when compared with those in polydatin
      group. In addition, the mRNA expression levels of AMPK-alpha2 and PPAR-alpha were
      slightly improved in combination group. The results illustrate that the
      combination of polydatin and vitamin C has the ability to enhance the myocardial
      protective effects by its antioxidative effect and improve energy metabolism.

PMID- 27891662
TI  - Acute mechanical hemolysis as a complication of extracorporeal photopheresis in a
      low-weight child.
AB  - Graft-versus-host disease (GVHD) is a complication of allogeneic hematopoietic
      stem cell transplantation with high morbidity and mortality. Extracorporeal
      photopheresis (ECP) is an effective therapy for treating medication-refractory
      GVHD, however, there is scant evidence of whether ECP can be safely performed in
      patients weighing less than 15 kg. Here, we report the implementation of a
      successful protocol to perform ECP in a 21-month-old, 10.6 kg female with
      medication-refractory GVHD. Our initial ECP treatment resulted in significant
      hemolysis that was most likely mechanical. After procedural adjustments that
      included modifying the anticoagulation dose and whole blood:anticoagulant ratio,
      as well as whole blood processing time, the patient tolerated future procedures
      safely without hemolysis or other adverse events. With appropriate technical
      modifications, we provide a framework for safely performing ECP in children less
      than 15 kg.

PMID- 27891664
TI  - Healthcare costs doubled when children had urinary tract infections caused by
      extended-spectrum beta-lactamase-producing bacteria.
AB  - AIM: The impact of the emergence of antimicrobial resistant organisms has rarely
      been studied in children, including the healthcare costs of urinary tract
      infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing
      bacteria. We evaluated the effect of ESBL on UTI healthcare costs and risk
      factors for paediatric UTIs. METHODS: This retrospective case-control study
      covered 2005-2014 and focused on children below 16 years of age treated in a
      University hospital: 22 children with UTIs caused by ESBL-producing bacteria and
      56 ESBL-negative UTI controls. RESULTS: The median healthcare costs were 3929
      Euros for the 22 ESBL patients and 1705 Euros for the 56 controls (p = 0.015).
      The mean and standard deviation length of hospital stay was 7.4 (5.9) days for
      the ESBL group and 3.6 (2.3) days for the controls (p = 0.007), and the figures
      for antibiotic treatment were 12.3 (5.5) days versus 5.8 (3.0) days (p < 0.001),
      respectively. The odd ratios for ESBL were underlying disease (6.63, p = 0.013),
      previous hospitalisation (6.07, p = 0.009) and antibiotic prophylaxis (5.20, p =
      0.035). CONCLUSION: Healthcare costs more than doubled when children had ESBL
      related UTIs, mainly due to their increased length of stay. Effective oral
      antibiotics are urgently needed to treat paediatric infections caused by ESBL
      producing bacteria.

PMID- 27891663
TI  - Extended-release niacin increases anti-apolipoprotein A-I antibodies that block
      the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE
      clinical trial.
AB  - AIMS: Extended-release niacin (ERN) is the most effective agent for increasing
      high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti
      HDL antibodies, we investigated whether ERN affected the antioxidant capacity of
      HDL and whether ERN was associated with the production of antibodies against HDL
      (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than
      18 years, with HDL-C <=40 mg dl-1 (men) or <=50 mg dl-1 (women) were randomly
      assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12
      week periods, with 4 weeks of wash-out before cross-over. Primary outcome was
      change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in
      aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006
      006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant
      (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53;
      P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient
      estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2
      (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3
      (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was
      significantly associated with the production of aApoA-I antibodies (coefficient
      estimate 0.25 MUg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline
      were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C
      achieved with ERN was not matched by improved antioxidant capacity, eventually
      hampered by the emergence of aApoA-I antibodies. These results may explain why
      Niacin and other lipid lowering agents fail to reduce cardiovascular risk.

PMID- 27891665
TI  - Spectral summation and facilitation in on- and off-responses for optimized
      representation of communication calls in mouse inferior colliculus.
AB  - Selectivity for processing of species-specific vocalizations and communication
      sounds has often been associated with the auditory cortex. The midbrain inferior
      colliculus, however, is the first center in the auditory pathways of mammals
      integrating acoustic information processed in separate nuclei and channels in the
      brainstem and, therefore, could significantly contribute to enhance the
      perception of species' communication sounds. Here, we used natural wriggling
      calls of mouse pups, which communicate need for maternal care to adult females,
      and further 15 synthesized sounds to test the hypothesis that neurons in the
      central nucleus of the inferior colliculus of adult females optimize their
      response rates for reproduction of the three main harmonics (formants) of
      wriggling calls. The results confirmed the hypothesis showing that average
      response rates, as recorded extracellularly from single units, were highest and
      spectral facilitation most effective for both onset and offset responses to the
      call and call models with three resolved frequencies according to critical bands
      in perception. In addition, the general on- and/or off-response enhancement in
      almost half the investigated 122 neurons favors not only perception of single
      calls but also of vocalization rhythm. In summary, our study provides strong
      evidence that critical-band resolved frequency components within a communication
      sound increase the probability of its perception by boosting the signal-to-noise
      ratio of neural response rates within the inferior colliculus for at least 20%
      (our criterion for facilitation). These mechanisms, including enhancement of
      rhythm coding, are generally favorable to processing of other animal and human
      vocalizations, including formants of speech sounds.

PMID- 27891666
TI  - A systematic review of the outcomes reported in trials of medication review in
      older patients: the need for a core outcome set.
AB  - AIM: Medication review has been advocated as one of the measures to tackle the
      challenge of polypharmacy in older patients, yet there is no consensus on how
      best to evaluate its efficacy. This study aimed to assess outcome reporting in
      trials of medication review in older patients. METHODS: Randomized controlled
      trials (RCTs), prospective studies and RCT protocols involving medication review
      performed in patients aged 65 years or older in any setting of care were
      identified from: (1) a recent systematic review; (2) RCT registries of ongoing
      studies; (3) the Cochrane library. The type, definition, and frequency of all
      outcomes reported were extracted independently by two researchers. RESULTS: Forty
      seven RCTs or prospective published studies and 32 RCT protocols were identified.
      A total of 327 distinct outcomes were identified in the 47 published studies.
      Only one fifth (21%) of the studies evaluated the impact of medication reviews on
      adverse events such as drug reactions or drug-related hospital admissions. Most
      of the outcomes were related to medication use (n = 114, 35%) and healthcare use
      (n = 74, 23%). Very few outcomes were patient-related (n = 24, 7%). A total of
      248 distinct outcomes were identified in the 32 RCT protocols. Overall, the
      number of outcomes and the number and type of health domains covered by the
      outcomes varied largely. CONCLUSION: Outcome reporting from RCTs concerning
      medication review in older patients is heterogeneous. This review highlights the
      need for a standardized core outcome set for medication review in older patients,
      to improve outcome reporting and evidence synthesis.

PMID- 27891667
TI  - Re: Schaefer: Re: Oelke et al Unravelling detrusor underactivity: Development of
      a bladder outlet resistance-bladder contractility nomogram for adult male
      patients with lower urinary tract symptoms and Letter-to-the-Editor by Alison
      Bray and Michael Drinnan.

PMID- 27891668
TI  - Systematic mapping of the subchondral bone 3D microarchitecture in the human
      tibial plateau: Variations with joint alignment.
AB  - Tibial subchondral bone plays an important role in knee osteoarthritis (OA).
      Microarchitectural characterization of subchondral bone plate (SBP), underlying
      subchondral trabecular bone (STB) and relationships between these compartments,
      however, is limited. The aim of this study was to characterize the spatial
      distribution of SBP thickness, SBP porosity and STB microarchitecture, and
      relationships among them, in OA tibiae of varying joint alignment. Twenty-five
      tibial plateaus from end-stage knee-OA patients, with varus (n = 17) or non-varus
      (n = 8) alignment were micro-CT scanned (17 MUm/voxel). SBP and STB
      microarchitecture was quantified via a systematic mapping in 22 volumes of
      interest per knee (11 medial, 11 lateral). Significant within-condylar and
      between-condylar (medial vs. lateral) differences (p < 0.05) were found. In
      varus, STB bone volume fraction (BV/TV) was consistently high throughout the
      medial condyle, whereas in non-varus, medially, it was more heterogeneously
      distributed. Regions of high SBP thickness were co-located with regions of high
      STB BV/TV underneath. In varus, BV/TV was significantly higher medially than
      laterally, however, not so in non-varus. Moreover, region-specific significant
      associations between the SBP thickness and SBP porosity and the underlying STB
      microarchitecture were detected, which in general were not captured when
      considering the values averaged for each condyle. As subchondral bone changes
      reflect responses to local mechanical and biochemical factors within the joint,
      our results suggest that joint alignment influences both the medial-to-lateral
      and the within-condyle distribution of force across the tibia, generating
      corresponding local bony responses (adaptation) of both the subchondral bone
      plate and underlying subchondral trabecular bone microarchitecture. (c) 2016
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      35:1927-1941, 2017.

PMID- 27891669
TI  - A molecular dynamics study of the binary complexes of APP, JIP1, and the cargo
      binding domain of KLC.
AB  - Mutations in the amyloid precursor protein (APP) are responsible for the
      formation of amyloid-beta peptides. These peptides play a role in Alzheimer's and
      other dementia-related diseases. The cargo binding domain of the kinesin-1 light
      chain motor protein (KLC1) may be responsible for transporting APP either
      directly or via interaction with C-jun N-terminal kinase-interacting protein 1
      (JIP1). However, to date there has been no direct experimental or computational
      assessment of such binding at the atomistic level. We used molecular dynamics and
      free energy estimations to gauge the affinity for the binary complexes of KLC1,
      APP, and JIP1. We find that all binary complexes (KLC1:APP, KLC1:JIP1, and
      APP:JIP1) contain conformations with favorable binding free energies. For
      KLC1:APP the inclusion of approximate entropies reduces the favorability. This is
      likely due to the flexibility of the 42-residue APP protein. In all cases we
      analyze atomistic/residue driving forces for favorable interactions. Proteins
      2017; 85:221-234. (c) 2016 Wiley Periodicals, Inc.

PMID- 27891670
TI  - Biomechanical behavior of novel composite PMMA-CaP bone cements in an
      anatomically accurate cadaveric vertebroplasty model.
AB  - Vertebral compression fractures are caused by many factors including trauma and
      osteoporosis. Osteoporosis induced fractures are a result of loss in bone mass
      and quality that weaken the vertebral body. Vertebroplasty and kyphoplasty,
      involving cement augmentation of fractured vertebrae, show promise in restoring
      vertebral mechanical properties. Some complications however, are reported due to
      the performance characteristics of commercially available bone cements. In this
      study, the biomechanical performance characteristics of two novel composite (PMMA
      CaP) bone cements were studied using an anatomically accurate human cadaveric
      vertebroplasty model. The study involves mechanical testing on two functional
      cadaveric spinal unit (2FSU) segments which include monotonic compression and
      cyclical fatigue tests, treatment by direct cement injection, and microscopic
      visualization of sectioned vertebrae. The 2FSU segments were fractured, treated,
      and mechanically tested to investigate the stability provided by two novel bone
      cements; using readily available commercial acrylic cement as a control. Segment
      height and stiffness were tracked during the study to establish biomechanical
      performance. The 2FSU segments were successfully stabilized with all three cement
      groups. Stiffness values were restored to initial levels following fatigue
      loading. Cement interdigitation was observed with all cement groups. This study
      demonstrates efficient reinforcement of the fractured vertebrae through stiffness
      restoration. The pre-mixed composite cements were comparable to the commercial
      cement in their performance and interdigitative ability, thus holding promise for
      future clinical use. (c) 2016 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 35:2067-2074, 2017.

PMID- 27891671
TI  - Lacerated anterior mitral valve leaflet following percutaneous balloon
      valvuloplasty.

PMID- 27891673
TI  - IgG4-related disease-experience of 100 consecutive cases from a specialist
      centre.
AB  - AIMS: To describe the features of 100 consecutive cases referred to a single UK
      institution in which a diagnosis of IgG4-related disease (IgG4-RD) was under
      consideration. METHODS AND RESULTS: The histological features were reviewed by a
      single histopathologist, and cases were categorized according to the 2012 Boston
      criteria: Category 1-histologically highly suggestive of IgG4-RD; Category 2
      probable histopathological features of IgG4-RD; and Category 3-insufficient
      histopathological evidence of IgG4-RD. A 'global assessment' was performed with
      the available clinical information: Assessment group 1-'definite/very likely IgG4
      RD'; Assessment group 2-'possible IgG4-RD'; Assessment group 3-'not IgG4-RD'; and
      Assessment group 4-insufficient information. The mean IgG4+ plasma cell count and
      IgG4+/IgG+ ratio were highest in Category 1 [134/high-power field (HPF); 57%] and
      Assessment group 1 (113/HPF; 52%), and lowest in Category 3 (11/HPF; 18%) and
      Assessment group 3 (43/HPF; 31%) (Category comparison of IgG4+ count and ratio,
      both P < 0.001; Assessment group comparison of IgG4+ count, P < 0.0002; and
      Assessment group comparison of ratio, P = 0.04). A non-IgG4-RD diagnosis was rare
      in Category 1 (7%) but common in Category 2 (60%) and Category 3 (47%). Stromal
      reactions to neoplasia and chronic oral ulceration were simulants of IgG4-RD.
      CONCLUSIONS: The Boston criteria are linked to the likelihood of IgG4-RD. Other
      conditions may show some histological features of IgG4-RD. The likelihood of IgG4
      RD is much greater when the histological features reach the threshold for
      Category 1 than when they reach the thresholds for Categories 2 and 3. Despite
      the utility of the Boston criteria, this study highlights the crucial importance
      of careful clinicopathological correlation when a diagnosis of IgG4-RD is under
      consideration.

PMID- 27891672
TI  - Cardiac rhabdomyoma in an infant patient presenting with right ventricular
      outflow tract obstruction.

PMID- 27891674
TI  - Correction of atrial size mismatch during heart transplantation with the bicaval
      technique.

PMID- 27891675
TI  - Surgical management of infective endocarditis complicated by ischemic stroke.
AB  - Embolism to the central nervous system is a frequent and important complication
      of infective endocarditis. While early surgery improves outcomes in many groups
      of patients with infective endocarditis, ischemic stroke secondary to septic
      embolism carries the risk of hemorrhagic transformation and neurological
      deterioration with heparinization and cardiopulmonary bypass. We review the
      literature regarding the surgical management of infective endocarditis in
      patients with cerebral emboli.

PMID- 27891676
TI  - Sex-dependent independent prediction of incident diabetes by depressive symptoms.
AB  - OBJECTIVE: To study the predictive value of depressive symptoms (DeprSs) in a
      general population of Turkey for type 2 diabetes. METHODS: Responses to three
      questions served to assess the sense of depression. Cox regression analyses were
      used regarding risk estimates for incident diabetes, after exclusion of prevalent
      cases of diabetes. Mean follow-up consisted of 5.15 (+/-1.4) years. RESULTS:
      Depressive symptoms were present at baseline in 16.2% of the whole study sample,
      threefold in women than men. Reduced physical activity grade was the only
      significant covariate at baseline in men, while younger age and lower blood
      pressure were significantly different in women compared with those without DeprS.
      In men, presence of DeprS predicted incident diabetes at a significant 2.58-fold
      relative risk (95% confidence interval 1.03; 6.44), after adjustment for age,
      systolic blood pressure, and antidepressant drug usage. When further covariates
      were added, waist circumference remained the only significant predictor, while
      DepS was attenuated to a relative risk of 2.12 (95% confidence interval 0.83;
      5.40). DeprS was not associated with diabetes in women, whereas antidepressant
      drug usage only tended to be positively associated. CONCLUSION: Gender difference
      existed in the relationship between DeprS and incident diabetes. DeprS predicted
      subsequent development of diabetes in men alone, not in women. Copyright (c) 2016
      John Wiley & Sons, Ltd.

PMID- 27891677
TI  - Staurosporine scaffold-based rational discovery of the wild-type sparing
      reversible inhibitors of EGFR T790M gatekeeper mutant in lung cancer with analog
      sensitive kinase technology.
AB  - The human epidermal growth factor receptor (EGFR) has been established as an
      attractive target for lung cancer therapy. However, an acquired EGFR T790M
      gatekeeper mutation is frequently observed in patients treated with first-line
      anticancer agents such as gefitinib and erlotinib to cause drug resistance,
      largely limiting the application of small-molecule kinase inhibitors in EGFR
      targeted chemotherapy. Previously, the reversible pan-kinase inhibitor
      staurosporine and its several analogs such as Go6976 and K252a have been reported
      to selectively inhibit the EGFR T790M mutant (EGFRT790M ) over wild-type kinase
      (EGFRWT ), suggesting that the staurosporine scaffold is potentially to develop
      the wild-type sparing reversible inhibitors of EGFRT790M . Here, we
      systematically evaluated the inhibitor response of 28 staurosporine scaffold
      based compounds to EGFR T790M mutation at structural, energetic, and molecular
      levels by using an integrated in silico-in vitro analog-sensitive (AS) kinase
      technology. With the strategy, we were able to identify 4 novel wild-type sparing
      inhibitors UCN-01, UCN-02, AFN941, and SB-218078 with high or moderate
      selectivity of 30-, 45-, 5-, and 8-fold for EGFRT790M over EGFRWT , respectively,
      which are comparable with or even better than that of the parent compound
      staurosporine (24-fold). Molecular modeling and structural analysis revealed that
      van der Waals contacts and hydrophobic forces can form between the side chain of
      mutated residue Met790 and the pyrrolidinone moiety of inhibitor ligand UCN-02,
      which may simultaneously improve the favorable interaction energy between the
      kinase and inhibitor, and reduce the unfavorable desolvation penalty upon the
      kinase-inhibitor binding. A hydroxyl group of UCN-02 additional to staurosporine
      locates at the pyrrolidinone moiety, which can largely alter the electronic
      distribution of pyrrolidinone moiety and thus promote the intermolecular
      interaction with Met790 residue. This can well explain the measured higher
      selectivity of UCN-02 than staurosporine for mutant over wild-type kinase.

PMID- 27891678
TI  - Morphomechanics of dermis-A method for non-destructive testing of collagenous
      tissues.
AB  - BACKGROUND: Collagenous tissues store, transmit and dissipate elastic energy
      during mechanical deformation. In skin, mechanical energy is stored during
      loading and then is dissipated, which protects skin from mechanical failure.
      Thus, energy storage (elastic properties) and dissipation (viscous properties)
      are important characteristics of extracellular matrices (ECMs) that support the
      cyclic loading of ECMs without tissue failure. METHODS: Uniaxial stress-strain
      measurements on decellularized human dermis have been made and compared to
      results of a non-destructive technique involving optical coherence tomography
      (OCT) combined with vibrational analysis. In addition, Poisson's ratio has been
      determined for tensile deformation of decellularized dermis. RESULTS: The modulus
      of decellularized dermis measured using standard tensile stress-strain tests and
      that determined from calculations derived from natural frequency measurements
      give similar results. It is also observed that Poisson's ratio for dermis is
      between 0.38 and 0.63 after correction for changes in volume that occur during
      tensile deformation. These results suggest that the assumption that dermis and
      other ECMs deform at constant volume is incorrect and will lead to differences in
      the calculated modulus by conventional tensile stress-strain measurements.
      CONCLUSIONS: It is proposed that OCT in conjunction with vibrational analysis is
      a convenient way to non-destructively measure the modulus of decellularized
      dermis, ECMs and other materials that have a positive curvature to their stress
      strain curves. Tensile deformation of dermis and possibly other ECMs is
      associated with an increase in Poisson's ratio consistent with a model of fluid
      expulsion from collagen fibrils during stretching. The value of Poisson's ratio
      should be considered in analyzing the mechanical properties of ECMs since at
      least dermis appears to be compressible during tensile deformation. Fluid
      expression during tensile deformation may play a role in mechanotransduction in
      skin in a similar manner to cartilage and bone tissue.

PMID- 27891680
TI  - ISUOG consensus statement on current understanding of the association of
      neurodevelopmental delay and congenital heart disease: impact on prenatal
      counseling.

PMID- 27891679
TI  - Adenylyl cyclase 3/adenylyl cyclase-associated protein 1 (CAP1) complex mediates
      the anti-migratory effect of forskolin in pancreatic cancer cells.
AB  - Pancreatic cancer is one of the most lethal human malignancies. A better
      understanding of the intracellular mechanism of migration and invasion is
      urgently needed to develop treatment that will suppress metastases and improve
      overall survival. Cyclic adenosine monophosphate (cyclic AMP) is a second
      messenger that has shown to regulate migration and invasion of pancreatic cancer
      cells. The rise of cyclic AMP suppressed migration and invasion of pancreatic
      ductal adenocarcinoma cells. Cyclic AMP is formed from cytosolic ATP by the
      enzyme adenylyl cyclase (AC). There are ten isoforms of ACs; nine are anchored in
      the plasma membrane and one is soluble. What remains unknown is the extent to
      which the expression of transmembrane AC isoforms is both modified in pancreatic
      cancer and mediates the inhibitory effect of forskolin on cell motility. Using
      real-time PCR analysis, ADCY3 was found to be highly expressed in pancreatic
      tumor tissues, resulting in a constitutive increase in cyclic AMP levels. On the
      other hand, ADCY2 was down-regulated. Migration, invasion, and filopodia
      formation in two different pancreatic adenocarcinoma cell lines, HPAC and PANC-1
      deficient in AC1 or AC3, were studied. We found that AC3, upon stimulation with
      forskolin, enhanced cyclic AMP levels and inhibited cell migration and invasion.
      Unlikely to be due to a cytotoxic effect, the inhibitory effects of forskolin
      involved the quick formation of AC3/adenylyl cyclase-associated protein 1
      (CAP1)/G-actin complex, which inhibited filopodia formation and cell motility.
      Using Western blotting analysis, forskolin, through AC3 activation, caused
      phosphorylation of CREB, but not ERK. The effect of CREB phosphorylation is
      likely to be associated with long-term signaling changes. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27891681
TI  - Incomplete Re-Expression of Neuroendocrine Progenitor/Stem Cell Markers is a Key
      Feature of beta-Cell Dedifferentiation.
AB  - There is increasing evidence to suggest that type 2 diabetes mellitus (T2D), a
      pandemic metabolic disease, may be caused by beta-cell dedifferentiation
      (betaCD). However, there is currently no universal definition of betaCD, and the
      underlying mechanism is poorly understood. We hypothesise that a high-glucose in
      vitro environment mimics hyperglycaemia in vivo and that beta cells grown in this
      milieu over a long period will undergo dedifferentiation. In the present study,
      we report that the pancreatic beta cell line mouse insulinoma 6 (MIN6) grown
      under a high-glucose condition did not undergo massive cell death but exhibited a
      glucose-stimulated insulin-secreting profile similar to that of immature beta
      cells. The expression of insulin and the glucose-sensing molecule glucose
      transporter 2 (Glut2) in late passage MIN6 cells was significantly lower than the
      early passage at both the RNA and protein levels. Mechanistically, these cells
      also expressed significantly less of the 'pancreatic and duodenal homebox1'
      (Pdx1) beta-cell transcription factor. Finally, passaged MIN6 cells
      dedifferentiated to demonstrate some features of beta-cell precursors, as well as
      neuroendocrine markers, in addition to expressing both glucagon and insulin.
      Thus, we concluded that high-glucose passaged MIN6 cells passaged MIN6 cells.
      provide a cellular model of beta-cell dedifferentiation that can help researchers
      develop a better understanding of this process. These findings provide new
      insights that may enhance knowledge of the pathophysiology of T2D and facilitate
      the establishment of a novel strategy by which this disease can be treated.

PMID- 27891682
TI  - Robust Min-system oscillation in the presence of internal photosynthetic
      membranes in cyanobacteria.
AB  - The oscillatory Min system of Escherichia coli defines the cell division plane by
      regulating the site of FtsZ-ring formation and represents one of the best
      understood examples of emergent protein self-organization in nature. The
      oscillatory patterns of the Min-system proteins MinC, MinD and MinE (MinCDE) are
      strongly dependent on the geometry of membranes they bind. Complex internal
      membranes within cyanobacteria could disrupt this self-organization by sterically
      occluding or sequestering MinCDE from the plasma membrane. Here, it was shown
      that the Min system in the cyanobacterium Synechococcus elongatus PCC 7942
      oscillates from pole-to-pole despite the potential spatial constraints imposed by
      their extensive thylakoid network. Moreover, reaction-diffusion simulations
      predict robust oscillations in modeled cyanobacterial cells provided that
      thylakoid network permeability is maintained to facilitate diffusion, and suggest
      that Min proteins require preferential affinity for the plasma membrane over
      thylakoids to correctly position the FtsZ ring. Interestingly, in addition to
      oscillating, MinC exhibits a midcell localization dependent on MinD and the
      DivIVA-like protein Cdv3, indicating that two distinct pools of MinC are
      coordinated in S. elongatus. Our results provide the first direct evidence for
      Min oscillation outside of E. coli and have broader implications for Min-system
      function in bacteria and organelles with internal membrane systems.

PMID- 27891683
TI  - Supramolecular Adaptive Nanomotors with Magnetotaxis Behavior.
AB  - With a convenient bottom-up approach, magnetic metallic nickel is grown in situ
      of a supramolecular nanomotor using the catalytic activities of preloaded
      platinum nanoparticles. After introducing magnetic segments, simultaneous
      guidance and steering of catalytically powered motors with additional magnetic
      fields are achieved. Guided motion in a tissue model is demonstrated.

PMID- 27891684
TI  - Changes in visibility as a function of spatial frequency and microsaccade
      occurrence.
AB  - Fixational eye movements (FEMs), including microsaccades, drift, and tremor,
      shift our eye position during ocular fixation, producing retinal motion that is
      thought to help visibility by counteracting neural adaptation to unchanging
      stimulation. Yet, how each FEM type influences this process is still debated.
      Recent studies found little to no relationship between microsaccades and visual
      perception of spatial frequencies (SF). However, these conclusions were based on
      coarse analyses that make it hard to appreciate the actual effects of
      microsaccades on target visibility as a function of SF. Thus, how microsaccades
      contribute to the visibility of stimuli of different SFs remains unclear. Here,
      we asked how the visibility of targets of various SFs changed over time, in
      relationship with concurrent microsaccade production. Participants continuously
      reported on changes in target visibility, allowing us to time-lock ongoing
      changes in microsaccade parameters to perceptual transitions in visibility.
      Microsaccades restored/increased the visibility of low SF targets more
      efficiently than that of high SF targets. Yet, microsaccade rates rose before
      periods of increased visibility, and dropped before periods of diminished
      visibility, for all the SFs tested, suggesting that microsaccades boosted target
      visibility across a wide range of SFs. Our data also indicate that visual stimuli
      fade/become harder to see less often in the presence of microsaccades. In
      addition, larger microsaccades restored/increased target visibility more
      effectively than smaller microsaccades. These combined results support the
      proposal that microsaccades enhance visibility across a broad variety of SFs.

PMID- 27891685
TI  - The DNA aptamer binds stemness-enriched cancer cells in pancreatic cancer.
AB  - Pancreatic cancer remains one of the most common and lethal cancers. Most
      patients (80%) present with inoperable advanced pancreatic cancer at initial
      diagnosis, and their early diagnosis is a significant unmet challenge. Recent
      studies indicate that cancer, including pancreatic cancer, is initiated and
      propagated by cancer stem cells (CSCs). CSCs are responsible not only for the
      pathogenesis of cancer but also for the heterogeneity, malignant degree,
      anticancer therapy resistance, and recurrence of tumors. Therefore, the
      identification of CSCs may be a crucial stepping stone for overcoming this
      disastrous pancreatic cancer. Here, we investigated pancreatic CSC-associated
      aptamers as a novel tool for diagnosis and therapeutic agents. Aptamers that bind
      to stemness-enriched cancer cells in pancreatic cancer were developed by modified
      Cell-SELEX method. Positive selection was performed by the sphere cells generated
      by pancreatic cancer cell line, HPAC, and then the aptamer pool was negatively
      selected by pancreatic normal cell line, HPDE. Aptamers 1 and 146 showing high
      specificity upon the KD values with 22.18 and 22.62 nM were selected. These 2
      aptamers were validated by binding to HPAC sphere cells and to HPDE cells, and
      both aptamers showed specificity to HPAC sphere cells only. Aptamer-positive
      cells showed high expression levels of CSC-associated genes compared with the
      aptamer-negative cells by FACS analysis. The colocalization of CD44, CD24, ESA,
      and CD133 was also observed in the aptamer-positive cells by confocal microscopy.
      In the present study, these 2 pancreatic CSC-associated aptamers may be potential
      candidates for novel diagnostic markers, CSC-targeting drug delivery, or
      circulating tumor cell detection.

PMID- 27891686
TI  - Implementation of a real-time reference and calibration grid platform for
      improved screening - mapping in Pap test slides.
AB  - Cervical cancer screening based on the Papanicolaou (Pap) test is a widely
      applied but not always efficient practice for detecting Human Papillomavirus
      (HPV) mediated lesions, partially due to a non-systematic and inadequate
      screening process. Our aim was to introduce an inexpensive easy-to-use direct
      screening platform for improved detection of abnormal cells indicative of
      underlying cervical neoplasia as well as persisting HPV infection. By employing a
      novel, efficient technique of laser-based micromachining, we achieved the
      fabrication of spatial grids on commercially available coverslips allowing visual
      segmentation of the slide for efficient screening. Abnormal and formerly
      diagnosed as negative for intraepithelial lesion or malignancy (NILM) Pap test
      slides (n = 200) were analyzed by conventional and grid-based screening. Grid
      based microscopy led to a more reliable diagnosis compared to the conventional by
      identifying an increased number of abnormal cells (P = 0.001). It decreased
      borderline ASCUS, AGC diagnosis, increasing LSIL, HSIL and in situ AdenoCa
      detection rates closely related with biopsy (P = 0.015; kappa = 0.978).
      Concerning the set of NILM diagnoses in rapid re-screening, the method upgraded
      six cases (n = 6) to LSIL (P = 0.001). The proposed technical solution offers a
      calibration and orientation visual aid during the on-site screening process
      providing significant advantages compared to expensive digital imaging
      techniques.

PMID- 27891687
TI  - Effect of preceding stimulation on sound localization and its representation in
      the auditory midbrain.
AB  - Prior stimulation can influence the perception of sound source location. Some
      psychophysical sound localization procedures differ in the amount of prior
      stimulation, which may affect measures of localization accuracy. If and how
      particularly the number of preceding stimuli affects sound localization and the
      neural representation of sound source position has not been investigated so far
      and will be the focus of the present report. We trained Mongolian gerbils in a
      left/right discrimination task where the target stimulus was preceded by silence
      or followed a number of reference stimuli. Localization thresholds decreased with
      the number of references presented before the target stimulus. The smallest
      thresholds were found after the presentation of a train of 5 reference stimuli
      and after silence. We recorded from units in the inferior colliculus (IC) of
      anaesthetized gerbils using virtual-acoustic space stimuli mimicking the ones
      used in the behavioural task and applied signal detection theory to compare
      behavioural and neurometric thresholds. We found that neurometric thresholds
      based on spike rate information of single units covered a wide range of threshold
      values but only neurometric thresholds that were based on responses of small
      populations of IC units reached consistently thresholds we also observed in the
      behavioural experiment. Unlike behavioural thresholds, however, neurometric
      thresholds were independent of the number of reference stimuli suggesting that
      processing stages downstream from the IC might better reflect the effect of prior
      stimulation.

PMID- 27891688
TI  - Possible role of calcitonin gene-related peptide in trigeminal modulation of
      glomerular microcircuits of the rodent olfactory bulb.
AB  - Chemosensation in the mammalian nose comprises detection of odorants, irritants
      and pheromones. While the traditional view assigned one distinct sub-system to
      each stimulus type, recent research has produced a more complex picture. Odorants
      are not only detected by olfactory sensory neurons but also by the trigeminal
      system. Irritants, in turn, may have a distinct odor, and some pheromones are
      detected by the olfactory epithelium. Moreover, it is well established that
      irritants change odor perception and vice versa. A wealth of psychophysical
      evidence on olfactory-trigeminal interactions in humans contrasts with a paucity
      of structural insight. In particular, it is unclear whether the two systems
      communicate just by sharing stimuli, or whether neuronal connections mediate
      cross-modal signaling. One connection could exist in the olfactory bulb that
      performs the primary processing of olfactory signals and receives trigeminal
      innervation. In the present study, neuroanatomical tracing of the mouse ethmoid
      system illustrates how peptidergic fibers enter the glomerular layer of the
      olfactory bulb, where local microcircuits process and filter the afferent signal.
      Biochemical assays reveal release of calcitonin gene-related peptide from
      olfactory bulb slices and attenuation of cAMP signaling by the neuropeptide. In
      the non-stimulated tissue, the neuropeptide specifically inhibited the basal
      activity of calbindin-expressing periglomerular interneurons, but did not affect
      the basal activity of neurons expressing calretinin, parvalbumin, or tyrosine
      hydroxylase, nor the activity of astrocytes. This study represents a first step
      towards understanding trigeminal neuromodulation of olfactory-bulb microcircuits
      and provides a working hypothesis for trigeminal inhibition of olfactory signal
      processing. This article is protected by copyright. All rights reserved.

PMID- 27891689
TI  - Deficit in acoustic signal-in-noise detection in glycine receptor alpha3 subunit
      knockout mice.
AB  - Hearing is an essential sense for communication in animals and humans. Normal
      function of the cochlea of higher vertebrates relies on a fine-tuned interplay of
      afferent and efferent innervation of both inner and outer hair cells. Efferent
      inhibition is controlled via olivocochlear feedback loops, mediated mainly by
      acetylcholine, gamma-aminobutyric acid (GABA) and glycine, and is one of the
      first sites affected by synapto- and neuropathy in the development of hearing
      loss. While the functions of acetylcholine, GABA and other inhibitory
      transmitters within these feedback loops are at least partially understood,
      especially the function of glycine still remains elusive. To address this
      question, we investigated hearing in glycine receptor (GlyR) alpha3 knockout (KO)
      and wildtype (WT) mice. We found no differences in pure tone hearing thresholds
      at 11.3 and 16 kHz between the two groups as assessed by auditory brainstem
      response (ABR) measurements. Detailed analysis of the ABR waves at 11.3 kHz,
      however, revealed a latency decrease of wave III and an amplitude increase of
      wave IV in KO compared to WT animals. GlyRalpha3 KO animals showed significantly
      impaired prepulse inhibition of the auditory startle response in a noisy
      environment, indicating that GlyRalpha3-mediated glycinergic inhibition is
      important for signal-in-noise detection.

PMID- 27891690
TI  - Alcohol's contribution to cancer is underestimated for exactly the same reason
      that its contribution to cardioprotection is overestimated.

PMID- 27891691
TI  - Probing metabolite diffusion at ultra-short time scales in the mouse brain using
      optimized oscillating gradients and "short"-echo-time diffusion-weighted MRS.
AB  - Measuring diffusion at ultra-short time scales may yield information about short
      range intracellular structure and cytosol viscosity. However, reaching such time
      scales usually requires oscillating gradients, which in turn imply long echo
      times TE . Here we propose a new kind of stretched oscillating gradient that
      allows us to increase diffusion-weighting b while preserving spectral and
      temporal properties of the gradient modulation. We used these optimized gradients
      to measure metabolite diffusion in the mouse brain down to effective diffusion
      times of 1 ms while keeping TE relatively short (60 ms). At such TE , a
      significant macromolecule signal could still be observed and used as an internal
      reference of approximately null diffusivity, which proved critical to discard
      datasets corrupted by some motion artifact. The methods introduced here may be
      useful to improve the accuracy and precision of metabolite apparent diffusion
      coefficient measurements with oscillating gradients.

PMID- 27891692
TI  - SMARCE1 mutation screening in classification of clear cell meningiomas.
AB  - AIMS: Clear cell meningioma (CCM) is a rare subtype of meningioma and shows not
      only unusual histology, but also unique clinical features. Recently, SMARCE1
      mutations have been shown to cause spinal and cranial CCMs. We present 12 cases
      which were diagnosed with CCM in a single institution between 1997 and 2014, and
      investigate their SMARCE1 mutation status. METHODS AND RESULTS: To investigate
      the SMARCE1 mutation status of these tumours, we used a combination of Sanger
      sequencing and multiplex ligation-dependent probe amplification analysis and also
      performed SMARCE1 immunohistochemical staining. We found both SMARCE1 mutational
      hits, including novel SMARCE1 mutations, in six of eight tested patients.
      Immunohistochemical analysis showed loss of SMARCE1 protein staining in all but
      two cases. Two individuals who were diagnosed originally with CCM were negative
      for SMARCE1 mutations, but tested positive for NF2 mutations. As a result, these
      two tumours were re-analysed and eventually reclassified, as a microcystic and a
      mixed pattern of meningothelial meningioma with focal clear cell areas,
      respectively. CONCLUSIONS: These results expand the spectrum of pathogenic
      variants in SMARCE1 and show that mutation screening can help to facilitate
      meningioma classification. This may have implications for prognosis and future
      clinical management of patients, as CCMs are classed as grade II tumours, while
      microcystic and meningothelial meningiomas are classed as grade I.

PMID- 27891693
TI  - Understanding and learning from the diversification of cannabis supply laws.
AB  - BACKGROUND AND AIMS: Prohibitions on producing, distributing and selling cannabis
      are loosening in various jurisdictions around the world. This paper describes the
      diversification of cannabis supply laws and discusses the challenges to and
      opportunities for learning from these changes. METHODS: We document changes in
      cannabis supply laws that de jure legalized cannabis production for medical
      and/or non-medical purposes (excluding industrial hemp) in Australasia, Europe,
      North America and South America. We also highlight challenges to evaluating these
      legal changes based on our experiences studying cannabis laws and policies in the
      United States. FINDINGS: As of August 2016, two countries have passed laws to
      legalize large-scale cannabis production for non-medical purposes at the national
      (Uruguay) or subnational level (four US states). At least nine other countries
      legally allow (or will soon allow) cannabis to be supplied for medicinal
      purposes. Most of the changes in cannabis supply laws have occurred since 2010.
      The data available in most countries are inadequate for rigorously evaluating the
      changes in cannabis supply laws. CONCLUSION: The evidence base for assessing
      changes in cannabis supply laws remains weak. Efforts should focus upon
      collecting information about quantities consumed and market transactions as well
      as validating self-report surveys.

PMID- 27891694
TI  - Genetic variation in blue whales in the eastern pacific: implication for taxonomy
      and use of common wintering grounds.
AB  - Many aspects of blue whale biology are poorly understood. Some of the gaps in our
      knowledge, such as those regarding their basic taxonomy and seasonal movements,
      directly affect our ability to monitor and manage blue whale populations. As a
      step towards filling in some of these gaps, microsatellite and mtDNA sequence
      analyses were conducted on blue whale samples from the Southern Hemisphere, the
      eastern tropical Pacific (ETP) and the northeast Pacific. The results indicate
      that the ETP is differentially used by blue whales from the northern and southern
      eastern Pacific, with the former showing stronger affinity to the region off
      Central America known as the Costa Rican Dome, and the latter favouring the
      waters of Peru and Ecuador. Although the pattern of genetic variation throughout
      the Southern Hemisphere is compatible with the recently proposed subspecies
      status of Chilean blue whales, some discrepancies remain between catch lengths
      and lengths from aerial photography, and not all blue whales in Chilean waters
      can be assumed to be of this type. Also, the range of the proposed Chilean
      subspecies, which extends to the Galapagos region of the ETP, at least
      seasonally, perhaps should include the Costa Rican Dome and the eastern North
      Pacific as well.

PMID- 27891695
TI  - Downregulation of neuronal vasoactive intestinal polypeptide in Parkinson's
      disease and chronic constipation.
AB  - BACKGROUND: Chronic constipation (CC) is a common and severe gastrointestinal
      complaint in Parkinson's disease (PD), but its pathogenesis remains poorly
      understood. This study evaluated functionally distinct submucosal neurons in
      relation to colonic motility and anorectal function in PD patients with
      constipation (PD/CC) vs both CC and controls. METHODS: Twenty-nine PD/CC and 10
      Rome III-defined CC patients were enrolled. Twenty asymptomatic age-sex matched
      subjects served as controls. Colonic transit time measurement and conventional
      anorectal manometry were evaluated in PD/CC and CC patients. Colonoscopy was
      performed in all three groups. Colonic submucosal whole mounts from PD/CC, CC,
      and controls were processed for immunohistochemistry with antibodies for
      vasoactive intestinal polypeptide (VIP) and peripheral choline acetyltransferase,
      markers for functionally distinct submucosal neurons. The mRNA expression of VIP
      and its receptors were also assessed. KEY RESULTS: Four subgroups of PD/CC
      patients were identified: delayed colonic transit plus altered anorectal
      manometry (65%); delayed colonic transit (13%); altered manometric pattern (13%);
      and no transit and manometric impairment (9%). There were no differences in the
      number of neurons/ganglion between PD/CC vs CC or vs controls. A reduced number
      of submucosal neurons containing VIP immunoreactivity was found in PD/CC vs
      controls (P<.05). VIP, VIPR1, and VIPR2 mRNA expression was significantly reduced
      in PD/CC vs CC and controls (P<.05). CONCLUSIONS AND INFERENCES: Colonic motor
      and rectal sensory functions are impaired in most PD/CC patients. These
      abnormalities are associated with a decreased VIP expression in submucosal
      neurons. Both sensory-motor abnormalities and neurally mediated motor and
      secretory mechanisms are likely to contribute to PD/CC pathophysiology.

PMID- 27891696
TI  - Gender differences in chronic constipation on anorectal motility.
AB  - BACKGROUND: The epidemiology of chronic constipation (CC) skews toward female
      predominance, yet men make up an important component of those suffering from CC.
      We sought to determine whether there are sex-specific differences in symptoms and
      physiologic parameters on anorectal manometry (ARM). METHODS: We performed a case
      control analysis of sequential men and age-matched women (2:1 ratio) presenting
      for ARM as part of the evaluation of CC. We collected physiologic parameters
      derived from 3D high-resolution ARM in addition to the ROME III constipation
      module and the Pelvic Floor Distress Inventory 20 (PFDI-20) questionnaires. We
      analyzed univariate, sex-specific differences in ARM physiologic parameters and
      PFDI-20 parameters and adjusted for putative confounders using multivariate
      logistic regression. KEY RESULTS: Our study enrolled 80 men and 165 age-matched
      women. Men had a higher median sphincter resting pressure (81.2 vs 75.2 mm Hg,
      P=.01) and mean squeeze pressure (257.0 vs 170.5 mm Hg, P<.0001) than women.
      Although men reported significantly less severe straining and incomplete
      evacuation, they had greater mean rectoanal pressure differential (-106.7 vs 
      71.1 mm Hg, P<.0001), smaller mean defecation index (0.17 vs 0.27, P=.03) and
      higher volume threshold for urgency (115.2 v. 103.4 mL, P=.03). However, women
      were more likely to have abnormal balloon expulsion time (BET) than men (52.7% vs
      35.0%, P=.01). After multivariate analysis, male gender was the only independent
      predictor of a normal BET (OR: 0.48, 95% CI: 0.27-0.86, P=.01). CONCLUSIONS &
      INFERENCES: Men and women with CC differ with regard to symptom severity and
      physiologic parameters derived from ARM suggesting differences in their
      pathophysiology.

PMID- 27891698
TI  - Vaccination and unexplained sudden death risk in Taiwanese infants.
AB  - PURPOSE: In March 1992, eight infants who had died within 36 hours of receiving
      whole-cell pertussis vaccine (diphtheria, tetanus, and whole-cell pertussis
      [DTwP]) prompted the Taiwan health authorities to suspend its use. We conducted
      an investigation of vaccination and sudden unexplained infant death (SUID) and
      repeated it more recently after Taiwan switched to acellular pertussis vaccine
      (diphtheria, tetanus, and acellular pertussis [DTaP]) in 2010. METHODS: All SUIDs
      aged 31-364 days during 1990-1992 and 1996-2013 were selected from the death
      registration databases. The case-control investigation matched each case to two
      controls on clinic, sex, and birth date, whereas the follow-up self-controlled
      case series study compared risk of death during the 30-day post-vaccination risk
      periods with those in the control periods within the same case. RESULTS: Sudden
      unexplained infant death was associated with never receiving DTwP (odds ratio
      2.28, 95% confidence interval 1.25-4.15) in the case-control investigation. The
      odds ratios within 0-1, 2-7, 8-14, and 15-30 days of DTwP administration were
      1.18, 0.26, 0.50, and 0.77. In the 1996-2013 self-controlled case series studies,
      this temporal shift between DTwP and SUID was consistently observed for female
      (incidence rate ratio 1.70, 0.75, 1.01, and 0.84) but not male or DTaP
      recipients. A pooled analysis showed significant risk within 2 days of receiving
      DTwP in female infants (incidence rate ratio 1.66, 95% confidence interval 1.05
      2.60). CONCLUSIONS: Being unvaccinated and recent receipt of DTwP in female
      infants was significantly associated with SUID; the latter was consistent with a
      temporal shift pattern without overall increase in risk. The currently used
      pertussis vaccine, DTaP, did not increase risk of SUID. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27891699
TI  - Effects of oils on feed mildew and quality.
AB  - This study was performed to determine the effects of oils on feed mildew and feed
      quality. Under different moisture content conditions (10%, 13% and 16%), the
      basal feeds were supplemented with 4%, 6%, 8%, 10% and 12% soybean oil. In
      addition, at different moisture content levels (10%, 13% and 16%), the basal feed
      was supplemented with 12% of various types of oil (soybean, peanut, corn and
      fish). Subsequently, a mixed mold spore suspension was added. The feed samples
      were incubated at 28 degrees C, and the total mold, water activity (Aw),
      moisture, acid value, crude protein (CP), crude lipid (CL), crude ash (CA) and
      nitrogen-free extract (NFE) levels were determined at 15, 30, 45 and 60 days. The
      results showed no significant variations in the feed moisture, CP, CL, CA and NEF
      contents. However, the acid value gradually increased in the feed samples with an
      extended incubation time and increasing initial moisture. The feed moisture
      content was a critical factor controlling feed mildew, and high levels of oil
      supplementation caused an elevated Aw. Additionally, peanut oil promoted mold
      growth in feed. These results provide a reference for the production and
      scientific management of formulated feed.

PMID- 27891700
TI  - Factors predicting emotional cue-responding behaviors of nurses in Taiwan: An
      observational study.
AB  - OBJECTIVE: Responding to emotional cues is an essential element of therapeutic
      communication. The purpose of this study is to examine nurses' competence of
      responding to emotional cues (CRE) and related factors while interacting with
      standardized patients with cancer. METHODS: This is an exploratory and predictive
      correlational study. A convenience sample of registered nurses who have passed
      the probationary period in southern Taiwan was recruited to participate in 15
      minute videotaped interviews with standardized patients. The Medical Interview
      Aural Rating Scale was used to describe standardized patients' emotional cues and
      to measure nurses' CRE. The State-Trait Anxiety Inventory was used to evaluate
      nurses' anxiety level before the conversation. We used descriptive statistics to
      describe the data and stepwise regression to examine the predictors of nurses'
      CRE. RESULTS: A total of 110 nurses participated in the study. Regardless of the
      emotional cue level, participants predominately responded to cues with
      inappropriate distancing strategies. Prior formal communication training,
      practice unit, length of nursing practice, and educational level together explain
      36.3% variances of the nurses' CRE. CONCLUSIONS: This study is the first to
      explore factors related to Taiwanese nurses' CRE. Compared to nurses in other
      countries, Taiwanese nurses tended to respond to patients' emotional cues with
      more inappropriate strategies. We also identified significant predictors of CRE
      that show the importance of communication training. Future research and education
      programs are needed to enhance nurses' CRE and to advocate for emotion-focused
      communication.

PMID- 27891701
TI  - Depression treatment and healthcare expenditures among elderly Medicare
      beneficiaries with newly diagnosed depression and incident breast, colorectal, or
      prostate cancer.
AB  - OBJECTIVES: Depression is associated with high healthcare expenditures, and
      depression treatment may reduce healthcare expenditures. However, to date, there
      have not been any studies on the effect of depression treatment on healthcare
      expenditures among cancer survivors. Therefore, this study examined the
      association between depression treatment and healthcare expenditures among
      elderly with depression and incident cancer. METHODS: The current study used a
      retrospective longitudinal study design, the linked Surveillance, Epidemiology,
      and End Results-Medicare database. Elderly (>=66 years) fee-for-service Medicare
      beneficiaries with newly diagnosed depression and incident breast, colorectal, or
      prostate cancer (N = 1502) were followed for a period of 12 months after
      depression diagnosis. Healthcare expenditures were measured every month for a
      period of 12-month follow-up period. Depression treatment was identified during
      the 6-month follow-up period. The adjusted associations between depression
      treatment and healthcare expenditures were analyzed with generalized linear mixed
      model regressions with gamma distribution and log link after controlling for
      other factors. RESULTS: The average 1-year total healthcare expenditures after
      depression diagnosis were $38 219 for those who did not receive depression
      treatment; $42 090 for those treated with antidepressants only; $46 913 for those
      treated with psychotherapy only; and $51 008 for those treated with a combination
      of antidepressants and psychotherapy. As compared to no depression treatment,
      those who received antidepressants only, psychotherapy only, or a combination of
      antidepressants and psychotherapy had higher healthcare expenditures. However,
      second-year expenditures did not significantly differ among depression treatment
      categories. CONCLUSIONS: Among cancer survivors with newly diagnosed depression,
      depression treatment did not have a significant effect on expenditures in the
      long term.

PMID- 27891702
TI  - Facing spousal cancer during child-rearing years: The short-term effects of the
      Cancer-PEPSONE programme-a single-center randomized controlled trial.
AB  - OBJECTIVE: To measure the short-term effects of the Cancer-PEPSONE programme
      (CPP) on the partners' received and perceived social support, psychological
      distress, and quality of life (QOL), as well as explore the role of received
      social support as a mediator of the intervention effects. METHODS: Open single
      center randomized controlled trial, trial number 15982171(ISRCTN). Eligible
      participants were the partners of cancer patients who were concomitantly caring
      for minors (the well parents). The sample consisted of 35 participants randomly
      allocated to receive either intervention (n = 17) or support as usual (n = 18).
      At the 3-month follow-up (approximately 1 month after intervention), 24 continued
      to participate (intervention n = 13, control n = 11). The intervention group
      selected supporters to participate in CPP (N = 130). Data were obtained using
      validated questionnaire. RESULTS: The multivariate analysis of covariance
      revealed significant intervention effects (P = .03, eta2p  = 0.42), with main
      effects on received and perceived social support. A mediational analysis
      suggested that CPP may have indirect effects on QOL through received social
      support. CONCLUSIONS: Even though the long-term effects are yet to be studied,
      CPP seems to increase social support for the well parents' short term, which in
      turn may improve their QOL. Given the study's low sample size, further
      replications in larger samples are required.

PMID- 27891703
TI  - An investigation into the inhibitory function of serotonin in diffuse noxious
      inhibitory controls in the neuropathic rat.
AB  - BACKGROUND: Following neuropathy alpha2-adrenoceptor-mediated diffuse noxious
      inhibitory controls (DNIC), whereby a noxious conditioning stimulus inhibits the
      activity of spinal wide dynamic range (WDR) neurons, are abolished, and spinal 5
      HT7 receptor densities are increased. Here, we manipulate spinal 5-HT content in
      spinal nerve ligated (SNL) animals and investigate which 5-HT receptor mediated
      actions predominate. METHODS: Using in vivo electrophysiology we recorded WDR
      neuronal responses to von frey filaments applied to the hind paw before, and
      concurrent to, a noxious ear pinch (the conditioning stimulus) in isoflurane
      anaesthetised rats. The expression of DNIC was quantified as a reduction in WDR
      neuronal firing in the presence of conditioning stimulus and was investigated in
      SNL rats following spinal application of (1) selective serotonin reuptake
      inhibitors (SSRIs) citalopram or fluoxetine, or dual application of (2) SSRI plus
      5-HT7 receptor antagonist SB269970, or (3) SSRI plus alpha2 adrenoceptor
      antagonist atipamezole. RESULTS: DNIC were revealed in SNL animals following
      spinal application of SSRI, but this effect was abolished upon joint application
      of SSRI plus SB269970 or atipamezole. CONCLUSIONS: We propose that in SNL animals
      the inhibitory actions (quantified as the presence of DNIC) of excess spinal 5-HT
      (presumed present following application of SSRI) were mediated via 5-HT7
      receptors. The anti-nociception depends upon an underlying tonic noradrenergic
      inhibitory tone via the alpha2-adrenoceptor. SIGNIFICANCE: Following neuropathy
      enhanced spinal serotonin availability switches the predominant spinal 5-HT
      receptor-mediated actions but also alters noradrenergic signalling. We highlight
      the therapeutic complexity of SSRIs and monoamine modulators for the treatment of
      neuropathic pain.

PMID- 27891704
TI  - Isoflavone genistein inhibits estrogen-induced chloride and bicarbonate secretory
      mechanisms in the uterus in rats.
AB  - We hypothesized that genistein could affect the chloride (Cl- ) and bicarbonate
      (HCO3- ) secretory mechanisms in uterus. Ovariectomized female rats were given
      estradiol or estradiol plus progesterone with 25, 50, or 100 mg/kg/day genistein.
      Following completion of the treatment, uterine fluid Cl- and HCO3- concentrations
      were determined by in vivo uterine perfusion. Uteri were subjected for molecular
      biological analysis (Western blot, qPCR, and immunohistochemistry) to detect
      levels of expression of Cystic Fibrosis transmembrane regulator (CFTR), Cl- /HCO3
      exchanger (SLC26a6), Na+ /HCO3- cotransporter (SLC4a4), and estrogen receptor
      (ER)-alpha and beta. Coadministration of genistein resulted in decrease in Cl-
      and HCO3- concentrations and expression of CFTR, SLC26a6, SLC4a4, and ER-alpha
      and ER-beta in the uteri of estradiol-treated rats. In estradiol plus
      progesterone-treated rats, a significant increase in the above parameters were
      observed following high-dose genistein treatment except for the SLC24a4 level. In
      conclusion, genistein-induced changes in the uterus could affect the reproductive
      processes that might result in infertility.

PMID- 27891705
TI  - Spinal cord stimulation in experimental chronic painful diabetic polyneuropathy:
      Delayed effect of High-frequency stimulation.
AB  - BACKGROUND: Spinal cord stimulation (SCS) has been shown to provide pain relief
      in painful diabetic polyneuropathy (PDPN). As the vasculature system plays a
      great role in the pathophysiology of PDPN, a potential beneficial side-effect of
      SCS is peripheral vasodilation, with high frequency (HF) SCS in particular. We
      hypothesize that HF-SCS (500 Hz), compared with conventional (CON) or low
      frequency (LF)-SCS will result in increased alleviation of mechanical
      hypersensitivity in chronic experimental PDPN. METHODS: Diabetes was induced in 8
      week-old female Sprague-Dawley rats with an intraperitoneal injection of 65 mg/kg
      of streptozotocin (n = 44). Rats with a significant decrease in mechanical
      withdrawal response to von Frey filaments over a period of 20 weeks were
      implanted with SCS electrodes (n = 18). Rats were assigned to a cross-over design
      with a random order of LF-, CON-, HF- and sham SCS and mechanical withdrawal
      thresholds were assessed with von Frey testing. RESULTS: Compared with sham
      treatment, the average 50% WT score for 5 Hz was 4.88 g higher during stimulation
      (p = 0.156), and 1.77 g higher post-stimulation (p = 0.008). CON-SCS resulted in
      50% WT scores 5.7 g, and 2.51 g higher during (p = 0.064) and after stimulation
      (p < 0.004), respectively. HF-SCS started out with an average difference in 50%
      WT score compared with sham of 1.87 g during stimulation (p = 0.279), and
      subsequently the steepest rise to a difference of 5.47 g post-stimulation (p <
      0.001). CONCLUSIONS: We demonstrated a delayed effect of HF-SCS on mechanical
      hypersensitivity in chronic PDPN animals compared with LF-, or CON-SCS.
      SIGNIFICANCE: This study evaluates the effect of SCS frequency (5-500 Hz) on
      mechanical hypersensitivity in the chronic phase of experimental PDPN. High
      frequency (500 Hz) - SCS resulted in a delayed effect- on pain-related
      behavioural outcome in chronic PDPN.

PMID- 27891707
TI  - The use of salivary cortisol as an index of chronic stress that correlates with
      depression in prostate cancer patients.

PMID- 27891706
TI  - Rectal intussusception: can high resolution three-dimensional ano-rectal
      manometry compete with conventional defecography?
AB  - BACKGROUND: Three-dimensional high-resolution anorectal manometry (3DHRAM), used
      for exploring anorectal disorders, was recently developed, providing interesting
      topographic data for the diagnosis of pelvic floor disorders such as excessive
      perineal descent. The aim of our study was to define a diagnostic strategy based
      on selected 3DHRAM parameters to identify rectal intussusceptions (RI),
      considering conventional defecography (CD) as the gold standard. METHODS: All
      patients referred to our center in the previous 6 months for 3DHRAM to explore
      fecal incontinence or constipation, and who previously achieved CD, were
      eligible. 3DHRAM results were obtained for all classical parameters and the
      presence of a narrow band of high pressure in the anal canal during attempted
      defecation, which was recently found to be associated with RI in some studies.
      The sensitivity, specificity, and positive and negative predictive values were
      calculated for various 3DHRAM criterion in order to propose a diagnostic strategy
      for RI. KEY RESULTS: Twenty-six patients (66%) presented with RI on CD. On
      3DHRAM, according to our diagnostic strategy, the most relevant manometric
      criterion for the diagnosis of RI was the association of an anterior additional
      high-pressure area and an excessive perineal descent, with a positive predictive
      value of 100% [81.5-100], a specificity of 100% [75.3-100] and a sensibility of
      69.2% [48.2-85.7]. CONCLUSIONS & INFERENCES: In this study, 3DHRAM was used to
      diagnose RI, and we confirmed its use in the diagnosis of pelvic floor disorders.
      Further studies will be necessary to define classifications for these new
      anatomic data from 3DHRAM.

PMID- 27891708
TI  - N-acetyl cysteine in the treatment of trichotillomania.

PMID- 27891709
TI  - Effect of dietary kapok oil supplementation on growth performance, carcass
      traits, meat quality and sensory traits of pork in finishing-pigs.
AB  - Kapok seed and oil from the tropical zone are widely used as pig feed to harden
      porcine fat in Japan. This study evaluated the effect of dietary kapok oil
      supplementation on pork quality and sensory traits. Five Duroc pigs each were
      assigned to an experimental group supplemented with kapok oil and a control
      group. Dietary kapok oil supplementation had no effect on growth performance and
      intramuscular fat content in the Longissimus dorsi muscle (LM). Supplemental
      kapok oil increased saturated fatty acid contents in subcutaneous and
      intramuscular fat and decreased monounsaturated fatty acid levels (P < 0.05). Off
      flavor detection by a trained panel was higher in the experimental than the
      control group (P < 0.05), but tenderness, juiciness, texture and flavor intensity
      of LM chops were similar in both groups. The overall palatability of pork as
      judged by a consumer panel decreased with kapok oil supplementation (P < 0.01).
      These results indicate that while growth performance, intramuscular fat contents
      and carcass characteristics were unchanged, while dietary kapok oil
      supplementation makes firm fat to prevent inferior soft fat in pork, it can lower
      the palatability of pork due to a decrease in monounsaturated fatty acids.

PMID- 27891710
TI  - Psychosis with suicide attempt in Sneddon syndrome.

PMID- 27891711
TI  - Identifying the microbial taxa that consistently respond to soil warming across
      time and space.
AB  - Soil microbial communities are the key drivers of many terrestrial biogeochemical
      processes. However, we currently lack a generalizable understanding of how these
      soil communities will change in response to predicted increases in global
      temperatures and which microbial lineages will be most impacted. Here, using high
      throughput marker gene sequencing of soils collected from 18 sites throughout
      North America included in a 100-day laboratory incubation experiment, we
      identified a core group of abundant and nearly ubiquitous soil microbes that
      shift in relative abundance with elevated soil temperatures. We then validated
      and narrowed our list of temperature-sensitive microbes by comparing the results
      from this laboratory experiment with data compiled from 210 soils representing
      multiple, independent global field studies sampled across spatial gradients with
      a wide range in mean annual temperatures. Our results reveal predictable and
      consistent responses to temperature for a core group of 189 ubiquitous soil
      bacterial and archaeal taxa, with these taxa exhibiting similar temperature
      responses across a broad range of soil types. These microbial 'bioindicators' are
      useful for understanding how soil microbial communities respond to warming and to
      discriminate between the direct and indirect effects of soil warming on microbial
      communities. Those taxa that were found to be sensitive to temperature
      represented a wide range of lineages and the direction of the temperature
      responses were not predictable from phylogeny alone, indicating that temperature
      responses are difficult to predict from simply describing soil microbial
      communities at broad taxonomic or phylogenetic levels of resolution. Together,
      these results lay the foundation for a more predictive understanding of how soil
      microbial communities respond to soil warming and how warming may ultimately lead
      to changes in soil biogeochemical processes.

PMID- 27891712
TI  - "The song inside": "La cancion por dentro"-Individual and dyadic impact of breast
      cancer for caregivers of Latina survivors.

PMID- 27891713
TI  - Influence of glass composition on secondary ion mass spectrometry instrumental
      mass fractionation for Si and Ca isotopic analyses.
AB  - RATIONALE: In situ secondary ion mass spectrometry (SIMS) analysis requires the
      use of standards to unravel the instrumental mass fractionation (IMF) induced by
      the analytical procedures. Part of this IMF might be caused by the nature of the
      sample and the differences in composition and structure between the sample and
      the standards. This "matrix effect" has been tentatively corrected for by using
      standards with chemical compositions equivalent to the samples, or by the
      empirical use of chemical parameters. However, these corrections can only be
      applied to a narrow compositional range and fail to take proper account of the
      matrix effect when a wider chemical field is tested. METHODS: We synthesized a
      series of glasses whose compositions span a very large part of the NCMAS (Na2 O
      CaO-MgO-Al2 O3 -SiO2 ) system. Si and Ca isotopic analyses were performed on two
      ion microprobes (Cameca IMS-1270 and IMS-1280). RESULTS: The matrix effect
      observed may reach 200/00 between extreme compositions and cannot be accounted
      for by the previously used "chemical" parameters (e.g. SiO2 , SiO2 /(SiO2  + Al2
      O3 )) nor by the NBO/T parameter. It therefore appears necessary to consider not
      only the structure of the glasses, but also the nature of the different atoms.
      Consequently, we assessed the use of another concept, the optical basicity, based
      on the electronegativities of the constitutive elements of glass. CONCLUSIONS: We
      show that this parameter significantly improves the efficiency of the matrix
      effect correction and that it can be applied across the entire NCMAS
      compositional range studied here. Furthermore, the use of optical basicity
      reduces the number of glass standards required for a reliable isotopic study, and
      it can also be used to probe the structure of the glass. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27891714
TI  - Altered serum level of matrix metalloproteinase-9 and its association with
      decision-making in eating disorders.
AB  - AIM: The aims of this study were to determine whether the serum levels of
      precursor brain-derived neurotrophic factor (proBDNF), mature BDNF (mBDNF), and
      matrix metalloproteinase-9 (MMP-9) are altered in patients with eating disorders
      (ED), including anorexia nervosa (AN) and bulimia nervosa (BN), and to explore
      whether those levels are associated with decision-making abilities. METHODS:
      Nineteen women with AN, 28 women with BN, and 22 age-matched healthy control
      women (HC) were enrolled in the current study. All participants had their
      decision-making abilities assessed using the Iowa Gambling Task (IGT). Their
      eating-related pathophysiology and depressive/anxiety symptoms were also
      evaluated. RESULTS: The MMP-9 level in AN was significantly lower than that in
      either BN or HC, but the serum levels of proBDNF and mBDNF did not differ among
      the three groups. Investigation of the serum levels of proBDNF and MMP-9 in
      patients with ED and controls revealed a significant correlation between them. In
      the BN, there were positive correlations between mBDNF level and IGT performance
      and also between MMP-9 level and IGT performance, but these correlations did not
      occur in AN. The MMP-9 level was positively associated with the Symptom Scale,
      one of the subscales of the Bulimic Investigatory Test, Edinburgh, only in AN.
      CONCLUSION: These results suggest that the serum level of MMP-9 plays a role in
      the pathophysiology of AN, and both the serum levels of mBDNF and MMP-9 may be
      associated with decision-making abilities in patients with BN.

PMID- 27891716
TI  - Clinical characteristics of two patients with alpha1-antitrypsin Pittsburgh in a
      Chinese family.

PMID- 27891715
TI  - Baseline hepatitis B core antibody predicts treatment response in chronic
      hepatitis B patients receiving long-term entecavir.
AB  - Studies regarding the clinical significance of quantitative hepatitis B core
      antibody (anti-HBc) in patients with chronic hepatitis B receiving first-line
      nucleos(t)ide analogues is limited. The aim of this study was to determine the
      performance of anti-HBc as a predictor for hepatitis B e antigen (HBeAg)
      seroconversion in HBeAg-positive CHB patients treated with entecavir. This was a
      retrospective cohort study consisting of 139 Chinese patients enrolled in a
      multicenter clinical trial treated with entecavir or entecavir maleate for up to
      240 weeks. Anti-HBc evaluation was conducted for all the available samples using
      a newly developed double-sandwich anti-HBc immunoassay. At week 240, 35 (25.2%)
      patients achieved a serological response (HBeAg seroconversion) and these
      patients at week 240 had significantly higher levels of anti-HBc (P<.01). We
      defined 4.65 log10  IU.mL-1 , with a maximum sum of sensitivity and specificity,
      as the optimal cut-off value of baseline anti-HBc level to predict
      seroconversion. Patients with baseline anti-HBc >=4.65 log10  IU.mL-1 had 28.0%
      (26/93) and 35.5% (33/93) chance of seroconversion at weeks 144 and 240,
      respectively. The baseline anti-HBc level was the strongest predictor for
      seroconversion at week 144 (OR: 5.78, 95% confidence interval [CI]: 2.05-16.34,
      P=.001). The baseline anti-HBc level was a strong predictor for seroconversion at
      week 240 (OR: 5.36, 95% CI: 2.17-13.25, P<.001). Hence, baseline anti-HBc titre
      is a useful predictor of long-term entecavir therapy efficacy in HBeAg-positive
      CHB patients, which could be used to optimize antiviral therapy.

PMID- 27891717
TI  - Emerging climate-driven disturbance processes: widespread mortality associated
      with snow-to-rain transitions across 10 degrees  of latitude and half the range
      of a climate-threatened conifer.
AB  - Climate change is causing rapid changes to forest disturbance regimes worldwide.
      While the consequences of climate change for existing disturbance processes, like
      fires, are relatively well studied, emerging drivers of disturbance such as snow
      loss and subsequent mortality are much less documented. As the climate warms, a
      transition from winter snow to rain in high latitudes will cause significant
      changes in environmental conditions such as soil temperatures, historically
      buffered by snow cover. The Pacific coast of North America is an excellent test
      case, as mean winter temperatures are currently at the snow-rain threshold and
      have been warming for approximately 100 years post-Little Ice Age. Increased
      mortality in a widespread tree species in the region has been linked to warmer
      winters and snow loss. Here, we present the first high-resolution range map of
      this climate-sensitive species, Callitropsis nootkatensis (yellow-cedar), and
      document the magnitude and location of observed mortality across Canada and the
      United States. Snow cover loss related mortality spans approximately 10 degrees 
      latitude (half the native range of the species) and 7% of the overall species
      range and appears linked to this snow-rain transition across its range. Mortality
      is commonly >70% of basal area in affected areas, and more common where mean
      winter temperatures is at or above the snow-rain threshold (>0  degrees C mean
      winter temperature). Approximately 50% of areas with a currently suitable climate
      for the species (<-2  degrees C) are expected to warm beyond that threshold by
      the late 21st century. Regardless of climate change scenario, little of the range
      which is expected to remain suitable in the future (e.g., a climatic refugia) is
      in currently protected landscapes (<1-9%). These results are the first
      documentation of this type of emerging climate disturbance and highlight the
      difficulties of anticipating novel disturbance processes when planning for
      conservation and management.

PMID- 27891718
TI  - The association between hepatitis B self-awareness and depression: Exploring the
      modifying effects of socio-economic factors.
AB  - China has a high prevalence of HBV. Despite previous studies, uncertainty remains
      about the association of HBV with depression. This study explores the strength of
      the association and the modifying effects of participants' self-awareness of the
      disease and their socio-economic status. Data from the baseline of a Chinese
      cohort study of approximately 500 000 adults were analysed. Depression was
      assessed using the Composite International Diagnostic Inventory. Blood spot tests
      were conducted to detect hepatitis B surface antigen. Logistic regression was
      used to assess the association between depression and HBV adjusting for
      demographic, socio-economic and lifestyle factors of major depression. To
      understand the effect modifications of disease self-awareness and socio-economic
      factors, a series of stratified analyses were undertaken. The overall prevalence
      of HBV is 3.2%, with 2.8% screen-detected and 0.3% self-reported cases. There was
      an 84% increased odds of depression among self-reported HBV patients (OR=1.84,
      95% CI: 1.16-2.90), but no association was found in the screen-detected group
      (OR=0.98, 95% CI: 0.79-1.23). Male (OR=2.28, 95% CI: 1.30-3.98), younger age
      (OR=3.57, 95% CI: 1.82-7.00), rural resident (OR=2.31, 95% CI: 1.36-3.94), lower
      household income (OR=2.38, 95% CI: 1.34-4.25) and agricultural worker (OR=2.92,
      95% CI: 1.63-5.77) were found having greater odds of depression in the HBV self
      aware group, compared to those without HBV. A strong association between
      hepatitis B self-awareness and depression was found. Lower socio-economic status
      could modify the association between hepatitis B status and depression. Further
      studies are needed to understand the underlying psychosocial mechanisms of the
      association.

PMID- 27891719
TI  - Myocardial strain to detect subtle left ventricular systolic dysfunction.
AB  - In daily clinical practice, LV systolic function is routinely assessed with the
      use of two-dimensional echocardiography. Using biplane LV end-diastolic and end
      systolic volumes, LVEF is calculated. The introduction of real-time three
      dimensional echocardiography has improved the accuracy of echocardiographic
      assessment of LVEF. However, calculated LVEF may not truly represent LV systolic
      function in specific cardiac diseases or when subtle LV dysfunction is present.
      Two-dimensional speckle tracking echocardiography enables assessment of
      myocardial strain, thereby providing detailed information on global and regional
      LV deformation. This is of particular interest when subtle LV systolic
      dysfunction is present despite preserved LVEF. In this review, the potential use
      of LV global longitudinal strain to detect subtle LV systolic dysfunction is
      illustrated in various clinical scenarios.

PMID- 27891720
TI  - The Role of the Axial Substituent in Subphthalocyanine Acceptors for Bulk
      Heterojunction Solar Cells.
AB  - Four hexachlorosubphthalocyanines SubPcCl6 -X bearing different axial
      substituents (X) have been synthesized for use as novel electron acceptors in
      solution-processed bulk-heterojunction organic solar cells. Subphthalocyanines
      are aromatic chromophoric molecules with cone-shaped structure, good solution
      processability, intense optical absorption in the visible spectral region,
      appropriate electron mobilities, and tunable energy levels. Solar cells with
      subphthalocyanines as the electron acceptor and PTB7-Th as the electron donor
      exhibit a power conversion efficiency up to 4 % and an external quantum
      efficiency approaching 60 % due to significant contributions from both the
      electron donor and the electron acceptor to the photocurrent, indicating a
      promising prospect of non-fullerene acceptors based on subphthalocyanines and
      structurally related systems.

PMID- 27891721
TI  - Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis
      in children with severe haemophilia A.
AB  - INTRODUCTION: Primary factor VIII (FVIII) prophylaxis is the optimal treatment in
      children with severe haemophilia A. They are expected to benefit from extended
      half-life (T1/2 ) FVIII coverage by reduced infusion frequency while maintaining
      haemostatic efficacy. AIMS: To determine immunogenicity, pharmacokinetics (PK),
      efficacy, safety and quality of life of prophylaxis with a polyethylene glycol
      (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in
      paediatric previously treated patients (PTPs) with severe haemophilia A. METHODS:
      PTPs <12 years without history of FVIII inhibitors received twice-weekly
      infusions of 50 +/- 10 IU kg-1 BAX 855 for >=50 exposure days. Prophylactic dose
      increases to <=80 IU kg-1 were allowed under predefined conditions. PK was
      evaluated after single infusions of 60 +/- 5 IU kg-1 . RESULTS: T1/2 and mean
      residence time were extended 1.3- to 1.5-fold compared to ADVATE (n = 31),
      depending on the analysis used. The point estimate for the mean annualized
      bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3
      IU kg-1 of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16
      (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No
      bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of
      bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target
      joints resolved. No subject developed FVIII inhibitors or persistent binding
      antibodies that affected safety or efficacy. No adverse reactions occurred.
      CONCLUSION: Twice-weekly prophylaxis with BAX 855 was safe and efficacious in
      paediatric PTPs with severe haemophilia A.

PMID- 27891722
TI  - Flexible, Luminescent Metal-Organic Frameworks Showing Synergistic Solid-Solution
      Effects on Porosity and Sensitivity.
AB  - Mixing molecular building blocks in the solid solution manner is a valuable
      strategy to obtain structures and properties in between the isostructural parent
      metal-organic frameworks (MOFs). We report nonlinear/synergistic solid-solution
      effects using highly related yet non-isostructural, phosphorescent CuI triazolate
      frameworks as parent phases. Near the phase boundaries associated with
      conformational diversity and ligand heterogeneity, the porosity (+150 %) and
      optical O2 sensitivity (410 times, limit of detection 0.07 ppm) can be
      drastically improved from the best-performing parent MOFs and even exceeds the
      records hold by precious-metal complexes (3 ppm) and C70 (0.2 ppm).

PMID- 27891723
TI  - The Structured Assessment of Violence Risk in Adults with Intellectual
      Disability: A Systematic Review.
AB  - BACKGROUND: While structured professional judgement approaches to assessing and
      managing the risk of violence have been extensively examined in mental
      health/forensic settings, the application of the findings to people with an
      intellectual disability is less extensively researched and reviewed. This review
      aimed to assess whether risk assessment tools have adequate predictive validity
      for violence in adults with an intellectual disability. METHODS: Standard
      systematic review methodology was used to identify and synthesize appropriate
      studies. RESULTS: A total of 14 studies were identified as meeting the inclusion
      criteria. These studies assessed the predictive validity of 18 different risk
      assessment tools, mainly in forensic settings. All studies concluded that the
      tools assessed were successful in predicting violence. Studies were generally of
      a high quality. CONCLUSIONS: There is good quality evidence that risk assessment
      tools are valid for people with intellectual disability who offend but further
      research is required to validate tools for use with people with intellectual
      disability who offend.

PMID- 27891724
TI  - Establishing a canine superficial pyoderma model.
AB  - AIMS: Pyoderma, predominantly associated with Staphylococcus pseudintermedius, is
      a common skin infection of dogs that typically requires long-lasting treatments,
      complicated by increasing antimicrobial resistance. To investigate new treatment
      strategies, we aimed at establishing a dog model of pyoderma that closely mimics
      the natural disease. METHODS AND RESULTS: We inoculated six laboratory beagles
      with a methicillin-susceptible strain of S. pseudintermedius. One millilitre of
      approximately 107 , 108 , 109 CFU per ml was topically applied onto clipped and
      tape stripped area of dog skin, which was then treated with a dermaroller
      (microneedle size: 500 MUm) immediately after administration. Dogs were monitored
      daily, suspect pustules were cultured for S. pseudintermedius and evaluated by
      cytological and histopathological methods. After 24 h, all dogs developed papules
      and pustules at all three bacterial inoculation sites, which worsened over the
      next 48 h. Cytological samples of all skin lesions revealed neutrophils with
      intracellular cocci. Histopathology confirmed subcorneal neutrophilic pustular
      dermatitis with intralesional cocci and acantholytic keratinocytes, consistent
      with superficial pyoderma. Staphylococcus pseudintermedius was isolated from
      pustules of all dogs and confirmed to be the inoculating strain. The results were
      replicated in all dogs after a wash out period of 6 weeks. CONCLUSIONS: These
      data demonstrate the feasibility of establishing a dog model of pyoderma.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The new model can be used to evaluate novel
      prevention and treatment options for canine pyoderma.

PMID- 27891725
TI  - Cognitive task demands and discourse performance after traumatic brain injury.
AB  - BACKGROUND: Social communication problems are common in adults with traumatic
      brain injury (TBI), particularly problems in spoken discourse. Social
      communication problems are thought to reflect underlying cognitive impairments.
      AIMS: To measure the contribution of two cognitive processes, executive
      functioning (EF) and theory of mind (ToM), to the communication of adults with
      TBI, and to investigate the relationships between discourse performance and
      potential communication partners' perceptions. METHODS & PROCEDURES: Twenty-one
      adults with moderate-to-severe TBI and 23 uninjured adults completed a discourse
      task in which EF and ToM demands were manipulated across three conditions:
      baseline, high-EF and high-ToM. Dependent variables were fluency (for EFs),
      number of mental state terms (MSTs; for ToM) and speech rate. Discourse from high
      EF/ToM conditions was judged by naive raters for social acceptability. OUTCOMES &
      RESULTS: The TBI group produced significantly fewer MSTs than the comparison
      group across conditions and also spoke at a slower rate, and there were
      significant effects of condition on both measures (MST: high-EF < baseline = high
      ToM; speech rate: high-EF < high-ToM < baseline). There were no significant
      between-groups differences in fluency or interaction of fluency with condition.
      MST use and fluency were associated with social acceptability ratings.
      CONCLUSIONS & IMPLICATIONS: Results added further evidence of social
      communication problems in adults with TBI and demonstrated that discourse
      behaviours may negatively affect how a speaker is perceived. Results also
      indicated that task manipulations can affect discourse performance, suggesting
      that general cognitive demands may influence social communication after TBI.

PMID- 27891727
TI  - Rehospitalization after pediatric heart transplantation: Incidence, indications,
      and outcomes.
AB  - We report the patterns of rehospitalization after pediatric heart transplant
      (Htx) at a single center. Retrospective review of 107 consecutive pediatric Htx
      recipients between January 22, 2007, and August 28, 2014, who survived their
      initial transplant hospitalization. The frequency, duration, and indications for
      all hospitalizations between transplant hospitalization discharge and September
      30, 2015, were analyzed. A total of 444 hospitalization episodes occurred in 90
      of 107 (84%) patients. The median time to first rehospitalization was 59.5 (range
      1-1526) days, and the median length of stay was 2.5 (range 0-81) days. There were
      an average of two hospitalizations per patient in the first year following
      transplant hospitalization, declining to about 0.8 per patient per year starting
      at 3 years post-transplant. Admissions for viral infections were most common,
      occurring in 93 of 386 (24%), followed by rule out sepsis in 61 of 386 (16%).
      Admissions for suspected or confirmed rejection were less frequent, accounting
      for 41 of 386 (11%) and 31 of 386 (8%) of all admissions, respectively. Survival
      to discharge after rehospitalization was 97%. Hospitalization is common after
      pediatric Htx, particularly in the first post-transplant year, with the most
      frequent indications for hospitalization being viral illness and rule out sepsis.
      After the first post-transplant year, the risk for readmission falls
      significantly but remains constant for several years.

PMID- 27891728
TI  - Obesity-related male genital lichen sclerosus.
AB  - BACKGROUND: Obesity is increasing. Male genital lichen sclerosus (MGLSc) is
      almost exclusively a disease of the uncircumcised. An apparent increasing
      challenge is MGLSc in previously circumcised obese males. OBJECTIVES: To
      characterise patients with obesity-related MGLSc. METHODS: Case chart review of
      patients managed in specialist clinics. RESULTS: Nineteen patients with obesity
      related MGLSc were identified. All had been previously circumcised. 16 (84%)
      acknowledged urinary microincontinence ('dribbling'). 14 (74%) remitted with
      medical treatment and 5 (26%) needed specialised surgery. CONCLUSIONS: Male
      genital lichen sclerosus can complicate obesity in previously circumcised
      patients. Management requires dermatological and specialist urological input, and
      can be challenging, but effective. The phenomenon increases the evidence for the
      role of the occlusive influence of urine in the pathogenesis of MGLSc.

PMID- 27891726
TI  - Everyday conversation in dementia: a review of the literature to inform research
      and practice.
AB  - BACKGROUND: There has been increasing interest in dementia care in recent years,
      including how practitioners, service providers and society in general can help
      individuals to live well with the condition. An important aspect to this is
      provision of advice to ensure conversation partners effectively support the
      person with dementia in conversation. AIMS: To provide a descriptive review of
      the literature examining everyday conversation in dementia in order to inform
      practice and research. METHODS & PROCEDURES: This review used a method
      specifically developed for reviewing conversation analytic and related
      literature. A range of databases were searched using key words and explicitly
      described inclusion criteria leading to a final corpus of 50 titles. Using this
      qualitative methodology, each paper was examined and data extracted. The
      contribution of each of these is described and the implications for practice and
      research are outlined. MAIN CONTRIBUTION: This review examined studies into
      conversation in Alzheimer's disease, vascular dementia and Lewy body dementia,
      grouping these into: early influential studies; work drawing on positioning
      theory; studies using social and linguistic approaches; collaborative
      storytelling; formulaic language; studies specifically using conversation
      analysis; and conversation as a target for individualized therapy. In addition,
      more recent work examining primary progressive aphasia and behavioural variant
      frontotemporal dementia was explored. Overall, this review indicates that
      research examining conversation in natural settings provides a rich source of
      data to explore not just the challenges within conversation for those taking
      part, but also the skills retained by the person with dementia. An important
      aspect of this understanding is the notion that these skills relate not only to
      information exchange but also aspects of social interaction. The role of others
      in scaffolding the conversation abilities of the person with dementia and the
      potential of this for developing interventions are discussed. CONCLUSIONS &
      IMPLICATIONS: The review indicates that interventions targeting conversation in
      dementia are often advocated in the literature but currently such approaches
      remain to be systematically evaluated. In addition, many of the important
      insights arising from these studies have yet to inform multidisciplinary dementia
      care practice.

PMID- 27891729
TI  - Low prevalence of Aichi virus in molluscan shellfish samples from Galicia (NW
      Spain).
AB  - AIMS: The aim of this study was to detect and quantify Aichi virus (AiV) in
      shellfish from three estuaries in Galicia, the main producer of molluscs in
      Europe. METHODS AND RESULTS: A total of 249 shellfish samples were analysed using
      a reverse transcription-quantitative PCR procedure. AiV was detected in 15 of 249
      (6.02%) samples. Ria de Ares-Betanzos showed the highest prevalence (11.1%),
      followed by Ria do Burgo (3.7%) and Ria de Vigo, (2.56%). AiV quantifications
      ranged from nonquantifiable (under the limit of quantification of the method) to
      6.9 * 103 RNAc per g DT, with a mean value of 1.9 * 102 RNAc per g DT.
      CONCLUSION: Results obtained indicated that the prevalence of this enteric virus
      in the studied area is considerably lower than those of other enteric viruses,
      such as Norovirus, Sapovirus, HAV or HEV. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first study that detects the presence of AiV in shellfish from
      authorized harvesting areas in Spain. Further studies with clinical samples are
      needed to determine the potential risk of AiV for human health in Galicia.

PMID- 27891733
TI  - Generalized granulomatous dermatitis following Mycobacterium w (Mw) immunotherapy
      in lepromatous leprosy.
AB  - Mycobacterium w (Mw) vaccine is a heat-killed suspension derived from a
      nonpathogenic, cultivable, atypical mycobacterium named Mycobacterium indicus
      pranii. Mw immunotherapy has been reported to be efficacious as an adjunct to
      multidrug therapy multibacillary regimen in leprosy patients with high bacillary
      index. Cutaneous reactions are predominant adverse effects associated with the
      administration of vaccines. Cutaneous adverse effects ascribed to Mw vaccine are
      generally limited to the site of injection. We herein describe two cases of
      lepromatous leprosy who developed an unusual generalized cutaneous reaction
      following Mw immunotherapy. A high index of suspicion is needed to identify such
      manifestations in leprosy cases to avoid misdiagnosis of a relapse or a reaction
      and for appropriate treatment.

PMID- 27891730
TI  - Reduction in psoriasis related pruritus during biologic therapy.

PMID- 27891734
TI  - Impending skin necrosis after dermal filler injection: A "golden time" for first
      aid intervention.
AB  - Vascular compromise with impending skin necrosis is one of the most serious
      potential complications. Early recognition of vascular occlusion and swift and
      aggressive treatment are required to avoid any irreversible changes. However,
      initial symptoms of a vascular event are often dismissed as simple post
      procedural discomfort. If more than 3 days pass after filler injection, crust
      formation is initiated over the erythematous base along with a rim of fibrous
      tissue. Due to the replacement of normal tissues by fibrous material, the healing
      process may result in scar formation in spite of debridement and aggressive
      dressing changes. Scars often cause contracture and subsequent cosmetic
      disfigurement, which results in a traumatic burden to the patient. By sharing our
      experience of the patients with filler induced skin necrosis, we suggest that
      treatment should be initiated no later than 3 days after the procedure.

PMID- 27891736
TI  - Novel Organic Synthesis through Ultrafast Chemistry.
AB  - How fast are flashes? The field of flow chemistry has recently received
      increasing attention owing to the availability of commercial flow equipment. New
      syntheses with very short-lived intermediates have been enabled by sub
      millisecond mixing and reaction regimes in tailor-made flow devices.

PMID- 27891735
TI  - Hyperammonemia in ornithine transcarbamylase-deficient recipients following
      living donor liver transplantation from heterozygous carrier donors.
AB  - Ornithine transcarbamylase deficiency (OTCD) is a urea cycle disorder of X-linked
      inheritance, affecting the detoxification of excess nitrogen and leading to
      hyperammonemia (hyper-NH3 ). Living donor liver transplantation (LDLT) has been
      applied for the treatment of OTCD. This case series retrospectively reviewed two
      OTCD patients who experienced hyper-NH3 following LDLT. The first case was a 5
      year-old girl who had onset of OTCD at 2 years of age. Ornithine transcarbamylase
      (OTC) enzyme activity was 62% for the donor and 15% for the recipient. The
      patient suffered from recurrence of hyper-NH3 within 2 months following LDLT. The
      second case was a 5-year-old girl who had onset of OTCD at 3 years of age. OTC
      enzyme activity was 42.6% for the donor and 9.7% for the recipient. The patient
      suffered hyper-NH3 for 12 days starting on the date of surgery. Both of the
      patients transiently required continuous veno-venous hemodialysis; however, they
      are currently doing well without intensive medical treatment. The use of
      asymptomatic OTCD heterozygous donors in LDLT has been accepted with careful
      examination. However, an OTCD heterozygous carrier donor should be avoided if
      there is another donor candidate, due to the potentially fatal condition of hyper
      NH3 following LDLT.

PMID- 27891737
TI  - Role of resistance physical exercise in preventing testicular damage caused by
      chronic ethanol consumption in UChB rats.
AB  - Ethanol consumption is associated with spermatogenesis damage and testosterone
      level alterations. Alcohol remains the most commonly used substance among
      athletes and sports enthusiasts. This study evaluated whether resistance physical
      exercise can reduce the testicular damage caused by ethanol exposure. A total of
      36 ethanol drinking (UChB) rats were divided into four groups: C (control rats),
      ETOH (ethanol consumption), ETOH + T (ethanol consumption + physical training),
      and T (group physical training). The physical training component of the T and
      ETOH + T groups was based on a resistance training model consisting of four sets
      of 10 jumps, with an increasing overload of 50-70% of the body weight attached to
      the chest three times per week. Rats in the ETOH and ETOH +T groups received 10%
      ethanol. At postnatal day 90, the rats were sacrificed. Blood sample was
      collected for hormonal analysis, and the testicles were weighed and processed for
      histopathological, morphometric, and immunohistochemical analyses. The ETOH group
      showed an increase in testosterone levels. The immunohistochemical of androgen
      receptor and the absolute weight of the testes were higher in the ETOH and ETOH +
      T groups, while the ETOH animals showed a decreased weight gain index. The number
      of abnormal seminiferous tubules increased in the ETOH and T groups compared to
      those in the control group (C); however, the association with treatment (ETOH + T
      group) prevented this effect and decreased caspase-3 production. In conclusion,
      these findings show that the combination of ethanol consumption and resistance
      physical exercise can prevent testicular damage in adult UChB rats.

PMID- 27891738
TI  - Treatment of prurigo nodularis with lenalidomide.
AB  - Prurigo nodularis (PN) is an intensely pruriginous dermatological disorder whose
      treatment is challenging for dermatologists. It is characterized by eruptions of
      papules and hyperkeratotic nodules, some of which are eroded, on the extensor
      surfaces of the limbs. The most commonly used treatments for this condition are
      oral antihistamines and topical or systemic steroids. Thalidomide is an effective
      treatment option in cases of recalcitrant PN; however, its most frequent adverse
      effect is neurotoxicity, which often results in its discontinuation. Lenalidomide
      is an analogue of thalidomide that is more powerful and associated with less
      neurotoxicity than thalidomide. We report the third case of PN treated with
      lenalidomide, which involved a patient who was refractory to thalidomide.
      Lenalidomide may be a more effective treatment for PN than thalidomide and has a
      more favorable side effects profile than its counterpart.

PMID- 27891739
TI  - Acardiac twin pregnancies part IV: Acardiac onset from unequal embryonic
      splitting simulated by a fetoplacental resistance model.
AB  - BACKGROUND: Benirschke postulated that acardiac twinning occurs when markedly
      unequal embryonic splitting combines with arterioarterial (AA) and venovenous
      placental anastomoses. We tested this hypothesis by model simulations and by
      comparison of outcomes with 18 "pseudo-" (twin fetus with beating heart but
      otherwise with clear signs of an acardiac) and 3 "normal" acardiac cases.
      METHODS: The smaller/larger cell volume ratio at embryonic splitting becomes the
      smaller/larger embryonic/fetal blood volume ratio (a). From a, we derived
      nonpulsating blood pressures using normal values (larger twin) and normal values
      at an appropriate earlier gestational age (smaller twin). These unequal pressure
      sources were used in a linear resistance fetoplacental network to calculate
      umbilical venous diameter ratios. Acardiac onset occurs when the smaller twin has
      50% left of its normal, singleton placenta. Comparison with clinical cases
      approximated a by crown-rump-length-ratio to the 3rd power. Input parameters are
      a and the AA-radius at 40 weeks. RESULTS: Acardiacs can be small or large, can
      occur early or late, earlier at smaller a and larger AA, with larger umbilical
      venous diameter ratios at smaller a and smaller AA. Comparison with the 21
      clinical cases was good, except for 2. CONCLUSION: Our analysis supports
      Benirschke's hypothesis. The smaller twin has to share its placental perfusion
      with the larger twin, which is a novel finding. The AA size is essential for the
      future of both fetuses but complicates easy understanding of (pseudo-)acardiac
      clinical presentations. Late acardiac onset occurs infrequently. Using
      nonpulsating circulations may have caused our extensive predictions of late
      onset. An improved model requires including hypoxemia in the smaller twin from
      chronic placental hypoperfusion. Birth Defects Research 109:211-223, 2017. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27891741
TI  - Combination treatment of propranolol, minocycline, and tranexamic acid for
      effective control of rosacea.

PMID- 27891740
TI  - Minocycline successfully treats exaggerated granulomatous hypersensitivity
      reaction to Mw immunotherapy.
AB  - Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of
      leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety
      is limited. We report a series of eight patients who developed persisting
      injection site granulomatous reaction following Mw immunotherapy and were
      successfully treated with minocycline. Eight patients with persistent nodular
      swelling at the site of Mw injections were identified. Seven of them had received
      Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The
      lesions were firm, erythematous, succulent, non-tender nodules confined to the
      sites of Mw vaccine injections. In 6 of these patients nodules also involved the
      previously injected areas. Skin biopsy from all patients showed eosinophil rich
      inflammation admixed with histiocytes and lymphocytes. In addition granulomas
      were seen in all with septal and nodular panniculitis in four patients. Broken
      and granular acid-fast bacilli were identified in two cases. All patients were
      treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good
      clinical response. Granulomatous reaction is a rare but significant adverse
      effect of Mw immunotherapy at cosmetically and functionally imperative sites.
      Oral minocycline appears to be effective therapy in this situation.

PMID- 27891742
TI  - Stability of Perovskite Solar Cells: A Prospective on the Substitution of the A
      Cation and X Anion.
AB  - In recent years, organometal trihalide perovskites have emerged as promising
      materials for low-cost, flexible, and highly efficient solar cells. Despite their
      processing advantages, before the technology can be commercialized the poor
      stability of the organic-inorganic hybrid perovskite materials with regard to
      humidity, heat, light, and oxygen has be to overcome. Herein, we distill the
      current state-of-the-art and highlight recent advances in improving the chemical
      stability of perovskite materials by substitution of the A-cation and X-anion.
      Our hope is to pave the way for the rational design of perovskite materials to
      realize perovskite solar cells with unprecedented improvement in stability.

PMID- 27891743
TI  - Ingressive speech errors: a service evaluation of speech-sound therapy in a child
      aged 4;6.
AB  - BACKGROUND: A pattern of ingressive substitutions for word-final sibilants can be
      identified in a small number of cases in child speech disorder, with growing
      evidence suggesting it is a phonological difficulty, despite the unusual surface
      form. Phonological difficulty implies a problem with the cognitive process of
      organizing speech into sound contrasts. AIMS: To evaluate phonological therapy
      approaches in the remediation of non-pulmonic speech errors. Thus, adding to
      evidence concerning the nature of ingressive substitutions and their remediation
      whilst highlighting their occurrence within child speech disorder population for
      practising and training speech and language therapists. METHODS & PROCEDURES:
      Child KO, a boy aged 4;6, was identified through a screening of speech, language
      and communication needs at his school. Word-final, non-pulmonic-egressive
      substitutes for fricatives and plosives were identified using the Diagnostic
      Evaluation of Articulation and Phonology (DEAP). Treatment took place in five,
      weekly school-based sessions with a care-giver present, and targeted two phonemes
      /f/ and /?/ in word-final position. Word-final /s/ was monitored throughout to
      capture any change in other word-final fricatives. Phonemes /g/ and /p/ were used
      as controls, as no change was expected in word-final plosives as a result of
      therapy targeting fricatives. Production of single words in the DEAP, pre- and
      post-therapy were transcribed by two independent therapists, (transcription
      agreement was 86.6% (pre) and 83.7% (post), with all 140 consonants within the
      DEAP transcribed), and change in consonants correct was analysed using a Wilcoxon
      test. Picture description tasks and telling of familiar stories were videoed post
      therapy to analyse use of word-final fricative egression in connected speech.
      OUTCOME & RESULTS: Percentage consonants correct in single-words post-treatment
      was significantly higher than pre-treatment at single-word level. Generalization
      of target fricatives into connected speech and modest generalization of non
      target phonemes occurred. CONCLUSIONS & IMPLICATIONS: Although ingressive speech
      sounds are largely absent in the sound system of English, they do occur as speech
      sound errors in child speech disorder and respond to phonological therapy within
      the context of home and school environment. Therefore, training in the phonetic
      identification of speech sounds outside the system of English is essential.
      Additionally, non-lexical factors associated with ingression also influence the
      child's intelligibility and should be explored further in future research.

PMID- 27891744
TI  - Inducing speech errors in dysarthria using tongue twisters.
AB  - Although tongue twisters have been widely use to study speech production in
      healthy speakers, few studies have employed this methodology for individuals with
      speech impairment. The present study compared tongue twister errors produced by
      adults with dysarthria and age-matched healthy controls. Eight speakers (four
      female, four male; mean age = 54.5 years) with spastic (mixed-spastic) dysarthria
      of varying aetiology (cerebral palsy, multiple sclerosis, multiple system
      atrophy) and eight controls (four female, four male; mean age = 56.9 years) were
      audio-recorded producing tongue twisters. One word in each tongue twister was
      marked for prominence. Speakers with dysarthria produced significantly more
      errors and spoke slower than healthy controls. The effect of prominence was
      significant for both groups-words spoken with prosodic prominence were
      significantly less error prone compared with words without prominence. While both
      groups produced most errors on words in the third position (of four-word
      utterances), speakers with dysarthria also produced high rates of errors on the
      first and fourth words. This preliminary investigation demonstrated the promise
      of applying the tongue twister paradigm to speakers with dysarthria and
      contributes to the evidence base for the implementation of prosodic strategies in
      speech intervention.

PMID- 27891746
TI  - Enantioselective (4+2) Annulation of Donor-Acceptor Cyclobutanes by N
      Heterocyclic Carbene Catalysis.
AB  - Herein we report the enantioselective (4+2) annulation of donor-acceptor
      cyclobutanes and unsaturated acyl fluorides using N-heterocyclic carbene
      catalysis. The reaction allows a 3-step synthesis of cyclohexyl beta-lactones (25
      examples) in excellent chemical yield (most >=90 %) and stereochemical integrity
      (all >20:1 d.r., most >=97:3 e.r.). Mechanistic studies support ester enolate
      Claisen rearrangement, while derivatizations provide functionalized cyclohexenes
      and dihydroquinolinones.

PMID- 27891745
TI  - Cardiac extracellular matrix is associated with adverse outcome in patients with
      chronic heart failure.
AB  - AIMS: Accumulation of extracellular matrix (ECM) is known to play a crucial role
      in the pathophysiology of heart failure (HF). However, its prognostic relevance
      is poorly investigated. METHODS AND RESULTS: A total of 73 HF patients who
      underwent LV endomyocardial biopsy were enrolled in our study. ECM area was
      quantified by TissueFAXS and ImageJ software. Patients were followed-up at 6
      month intervals. The study endpoint was defined as hospitalization for a cardiac
      reason and/or cardiac death. Furthermore, the influence of the ECM on invasively
      measured haemodynamic parameters was tested. During a median follow-up period of
      9.0 months, 34 patients (46.6%) reached the combined endpoint. Median ECM area
      was 30.5%. Patients with ECM area >=30.5% experienced significantly more events
      (67.6% vs. 25.0%, P < 0.001) in comparison with patients with an ECM area <30.5%.
      ECM area was independently associated with outcome in the total HF cohort [hazard
      ratio (HR) 1.041, 95% confidence interval (CI) 1.017-1.066, P = 0.001] as well as
      in HF patients with preserved (HR 1.079, 95% CI 1.001-1.163, P =0 .046) or
      reduced ejection fraction (HR 1.149, 95% CI 1.036-1.275, P = 0.009). Positive
      correlations were found between ECM area and LV end-diastolic pressure (P =
      0.021, R = 0.303), pulmonary artery wedge pressure (P = 0.042, R = 0.249), mean
      pulmonary arterial pressure (P = 0.035, R = 0.258), as well as right atrial
      pressure (P = 0.003, R = 0.353). CONCLUSION: ECM area within the LV myocardium
      correlates with left and right heart haemodynamics and is associated with
      clinical course in various non-ischaemic HF types.

PMID- 27891747
TI  - Superacid-Catalyzed Trifluoromethylthiolation of Aromatic Amines.
AB  - Upon activation under superacid conditions, functionalized tailor-made N-SCF3
      sulfenamides served as reagents for the trifluoromethylthiolation of aromatic
      amines. This method has a broad substrate scope and can be used for the late
      stage functionalization of complex molecules such as alkaloids or steroids.
      Mechanistic studies based on in situ low-temperature NMR spectroscopy revealed
      the involvement of dicationic superelectrophilic intermediates.

PMID- 27891748
TI  - An Isosteric and Fluorescent DNA Base Pair Consisting of 4-aminophthalimide and
      2,4-diaminopyrimidine as C-Nucleosides.
AB  - A 13mer DNA duplex containing the artificial 4-aminophthalimide:2,4
      diaminopyrimidine (4AP:DAP) base pair in the central position was characterized
      by optical and NMR spectroscopy. The fluorescence of 4AP in the duplex has a
      large Stokes shift of Deltalambda=124 nm and a quantum yield of PhiF =24 %. The
      NMR structure shows that two interstrand hydrogen bonds are formed and confirms
      the artificial base pairing. In contrast, the 4-N,N-dimethylaminophthalimide
      moiety prefers the syn conformation in DNA. The fluorescence intensity of this
      chromophore in DNA is very low and the NMR structure shows no significant
      interaction with DAP. Primer-extension experiments with DNA polymerases showed
      that not only is the 4AP C nucleotide incorporated at the desired position
      opposite DAP in the template, but also that the polymerase is able to progress
      past this position to give the full-length product. The observed selectivity
      supports the NMR results.

PMID- 27891749
TI  - Chlorophyll-Derived Yellow Phyllobilins of Higher Plants as Medium-Responsive
      Chiral Photoswitches.
AB  - The fall colors are signs of chlorophyll breakdown, the biological process in
      plants that generates phyllobilins. Most of the abundant natural phyllobilins are
      colorless, but yellow phyllobilins (phylloxanthobilins) also occur in fall
      leaves. As shown here, phylloxanthobilins are unique four-stage photoswitches.
      Which switching mode is turned on is controlled by the molecular environment. In
      polar media, phylloxanthobilins are monomeric and undergo photoreversible Z/E
      isomerization, similar to that observed for bilirubin. Unlike bilirubin, however,
      the phylloxanthobilin Z isomers photodimerize in apolar solvents by regio- and
      stereospecific thermoreversible [2+2] cycloadditions from self-assembled hydrogen
      bonded dimers. X-ray analysis revealed the first stereostructure of a
      phylloxanthobilin and its hydrogen-bonded self-templating architecture, helping
      to rationalize its exceptional photoswitch features. The chemical behavior of
      phylloxanthobilins will play a seminal role in identifying biological roles of
      phyllobilins.

PMID- 27891751
TI  - Simultaneous determination of pyrifluquinazon and its main metabolite in fruits
      and vegetables by using QuEChERS-HPLC-MS/MS.
AB  - A rapid, reliable, and sensitive method is reported for the simultaneous analysis
      of pyrifluquinazon and its main metabolite NNI-0101-1H in fruits (strawberry and
      cherry) and vegetables (cucumber and tomato) using high-performance liquid
      chromatography coupled with tandem mass spectrometry. A modified, quick, easy,
      cheap, effective, rugged, and safe procedure was used for the sample pre
      preparation. The target analytes were extracted with acetonitrile and then
      cleaned up using dispersive solid-phase extraction procedure with primary
      secondary amine. Sample analysis was performed using electrospray ionization in
      positive mode. Good linearities with the correlation coefficients higher than
      0.9991 were obtained in the range of 1-1000 MUg/L under the optimized conditions.
      The average recoveries of the pyrifluquinazon and NNI-0101-1H were in the range
      of 71.4-106.0% with the relative standard deviations 1.8-11.8% in all matrices at
      three spiked levels (10, 100, and 1000 MUg/kg). The limit of quantification 10
      MUg/kg was set as the lowest spiked level. The developed method is reliable and
      effective for the routine monitoring of pyrifluquinazon and its metabolite NNI
      0101-1H in fruits and vegetables to ensure food safety.

PMID- 27891750
TI  - Epidemiology and outcomes of primary sclerosing cholangitis with and without
      inflammatory bowel disease in an Australian cohort.
AB  - BACKGROUND & AIMS: Epidemiological data on primary sclerosing cholangitis (PSC)
      outside the Northern hemisphere are limited. Similarly, the impact of
      inflammatory bowel disease (IBD) on PSC outcomes remains unclear. We aimed to
      study the epidemiology and outcomes of PSC patients with and without IBD in an
      Australian cohort. METHODS: We retrospectively studied PSC patients attending two
      tertiary referral hospitals over 20 years. Diagnosis of PSC was made according to
      international guidelines by positive cholangiography and/or liver biopsy (for
      small duct PSC) with supporting clinical and laboratory evidence. RESULTS: Of 208
      PSC patients (61% male) were studied (2271patient-years follow-up). The median
      age of PSC diagnosis was similar for PSC-IBD and PSC-only patients (40 years vs
      42 years, P = .35). All 33 deaths occurred in PSC-IBD patients while there were
      no deaths in PSC-only patients (21% vs 0%, P < .01). However, there were no
      significant differences in liver transplantation (PSC-only 25% vs PSC-IBD 31%, P
      = .45) and transplant-free survival between PSC-only and PSC-IBD patients (P =
      .43). On multivariate Cox regression, only elevated international normalized
      ratio (INR) was associated with a greater risk of death or liver transplant (HR
      2.0, 95% CI 1.1-3.6, P = .02). Development of gastrointestinal malignancy was
      higher in the PSC-IBD group compared to PSC-only group (22% vs 2%, P < .01).
      CONCLUSION: Australian PSC patients have similar characteristics compared to
      European and North American cohorts. IBD is a significant predictor of
      gastrointestinal malignancies. Deaths were more common in PSC-IBD but overall
      transplant-free survival remained similar in PSC-IBD and PSC-only groups. An
      elevated INR was an independent predictor of death or liver transplantation.

PMID- 27891753
TI  - Balzan Prize: R. Jahn / Honorary Membership of the Swiss Chemical Society: E. P.
      Kundig / KNCV Van Marumpenning: J. van Maarseveen / Emil Kirschbaum Medal: A.
      Seidel-Morgenstern.

PMID- 27891752
TI  - Switchable Surface Hydrophobicity-Hydrophilicity of a Metal-Organic Framework.
AB  - Materials with surfaces that can be switched from high/superhydrophobicity to
      superhydrophilicity are useful for myriad applications. Herein, we report a metal
      organic framework (MOF) assembled from ZnII ions, 1,4-benzenedicarboxylate, and a
      hydrophobic carborane-based linker. The MOF crystal-surface can be switched
      between hydrophobic and superhydrophilic through a chemical treatment to remove
      some of the building blocks.

PMID- 27891754
TI  - Patients with Barrett's esophagus are hypersensitive to acid but hyposensitive to
      other stimuli compared with healthy controls.
AB  - BACKGROUND: Esophageal hyposensitivity has been observed in Barrett's esophagus
      and may contribute to its pathophysiology. However, studies are few, in
      particular those assessing different sensory modalities. We aimed to compare
      esophageal sensitivity to multimodal stimulation in patients with Barrett's
      esophagus and in healthy controls. METHODS: Twenty-three patients with Barrett's
      esophagus and 12 healthy controls were examined. A multimodal probe was placed in
      the lower esophagus. Mechanical, thermal, and electrical stimulation was applied
      followed by an acid perfusion test with 0.1 N hydrochloric acid. KEY RESULTS:
      Compared with controls, patients were hyposensitive to mechanical distension,
      heat, and electrical stimulation (all P<.05), but hypersensitive to acid (mean
      tolerated acid volume 57% lower, P=.001). A linear correlation between acid
      hypersensitivity and lower baseline impedance was found (P<.001). Patients had
      longer esophageal acid exposure time than controls (median acid exposure time 18
      vs 5%, P=.03). Asymptomatic patients (no reflux symptoms at baseline) were
      hyposensitive to mechanical distension, electrical stimulation, and acid
      perfusion (all P<.05) compared with symptomatic patients. CONCLUSIONS &
      INFERENCES: Patients with Barrett's esophagus exhibited acid hypersensitivity but
      hyposensitivity to other stimuli. Lower mucosal baseline impedance, a likely
      surrogate marker for impaired mucosal integrity, may explain the selective
      hypersensitivity to acid. On the other hand, the concurrent hyposensitivity may
      theoretically be explained by changes in central pain modulation. Patients with
      Barrett's esophagus seem to compose symptomatic and asymptomatic subgroups,
      showing different esophageal sensory profiles.

PMID- 27891755
TI  - Strategic Utilization of Multifunctional Carbene for Direct Synthesis of
      Carboxylic-Phosphinic Mixed Anhydride from CO2.
AB  - Direct synthesis of carboxylic-phosphinic mixed anhydrides has been achieved by
      treating carbon dioxide with N-phosphine oxide-substituted imidazolylidenes
      (PoxIms) that contain both nucleophilic carbene and electrophilic phosphorus
      moieties. This novel mixed anhydride was efficiently derivatized into an ester,
      an amide, and an unsymmetrical ketone via transformation into its corresponding
      imidazolium salt followed by a dual substitution reaction. The presented work
      used well-designed multifunctional carbene reagents to establish a novel utility
      for carbon dioxide in organic synthesis.

PMID- 27891756
TI  - Motility patterns in mouse colon: gastrointestinal dysfunction induced by
      anticancer chemotherapy.
AB  - Colon cancer is a leading cause of cancer-related death in humans. 5-Fluorouracil
      (5-FU), a major chemotherapy treatment, has been used for decades to fight
      numerous types of cancers, including breast, colon, and head and neck carcinomas.
      Unfortunately, a large proportion of patients treated with 5-FU develop
      toxicities that include diarrhea, mucositis, neutropenia, and vomiting. While the
      side effects of 5-FU are well known, the mechanisms underlying the induction of
      these unpleasant symptoms are poorly understood. The study by McQuade et al. in
      this issue of Neurogastroenterology & Motility provides important new potential
      explanations for the gastrointestinal (GI) dysfunction induced by 5-FU. These
      researchers carefully investigated an overlooked research area in which the
      symptoms of GI-motility dysfunction maybe due to an effect on the enteric nervous
      system. McQuade et al. delivered 5-FU treatment to mice and discovered an initial
      increase in GI transit (associated with acute intestinal inflammation), followed
      by a slowing in transit. Major differences were noted in characteristics of
      colonic migrating motor complexes. These effects maybe causally related to
      deficits in enteric ganglia or neurotransmission. Their study identified specific
      neurochemical classes of neurons in the myenteric plexus most affected by 5-FU.
      This is the first study to provide evidence that the functional intrinsic neural
      pathways within the enteric nervous system are likely impaired by 5-FU, leading
      to colonic dysmotility. This review will describe major patterns of motor
      activity in isolated whole mouse colon and how these patterns are modified by
      anticancer chemotherapy.

PMID- 27891757
TI  - Randomized, double-blind, phase III study to evaluate the efficacy and safety of
      once-daily treatment with alogliptin and metformin hydrochloride in Japanese
      patients with type 2 diabetes.
AB  - This randomized, double-blind, phase III study evaluated the efficacy and safety
      of once-daily treatment with alogliptin (25 mg once daily), alone or with
      metformin hydrochloride (500 mg once daily or 250 mg twice daily), in Japanese
      patients with type 2 diabetes. The primary endpoint was change in glycated
      haemoglobin (HbA1c) from baseline to the end of treatment (week 24). The least
      squares (LS) mean (standard error) change in HbA1c from baseline to the end of
      treatment (week 24) was 0.16 (0.072)% in alogliptin alone, -0.49 (0.049)% in
      alogliptin/metformin once daily, and -0.60 (0.049)% in alogliptin/metformin twice
      daily. The LS mean difference in HbA1c change from baseline between
      alogliptin/metformin once daily and alogliptin alone (alogliptin/metformin once
      daily minus alogliptin alone) was -0.65% (95% confidence interval [CI] -0.821, 
      0.480) and between alogliptin/metformin once daily and twice daily (once daily
      minus twice daily) was 0.11% (95% CI -0.026, 0.247). The overall frequency of
      adverse events was similar among the groups. This study showed that the efficacy
      of alogliptin/metformin once daily was superior to alogliptin alone and non
      inferior to alogliptin/metformin twice daily, and that alogliptin/metformin once
      daily was safe and well tolerated in Japanese patients with type 2 diabetes.

PMID- 27891758
TI  - Is work keeping us from acting healthy? How workplace barriers and facilitators
      impact nutrition and exercise behaviors.
AB  - The purpose of this study was to identify common barriers and facilitators to
      healthy nutrition and exercise behaviors in the workplace and examine their
      relationships to those actual daily health behaviors. We utilized a concurrent
      embedded mixed methods approach to collect data from 93 participants over the
      span of four days. Participants reported 2.80 nutrition and 3.28 exercise
      barriers on average over the 4 days, while reporting 2.93 nutrition and 1.98
      exercise facilitators in the same timeframe. Results indicated that workload and
      temptations around the office prevented nutritious eating; exercise behaviors
      were frequently hindered by workload. The most commonly mentioned eating
      facilitator was proper planning, while having time to exercise facilitated
      physical activity. Furthermore, the number of barriers reported negatively
      related to their respective health behaviors (i.e., more nutrition barriers
      translated to poorer nutrition habits) and facilitators were positively related
      to them, both overall and more so on the specific day they were reported. The
      implications of these finding show the importance of barriers/facilitators in the
      workplace and aid in the creation of more targeted health promotion that could
      increase positive employee health behaviors by eliminating common barriers and
      enhancing facilitators.

PMID- 27891759
TI  - Sociodemographic correlates and family aggregation of leukocyte telomere length
      in adults and children from Mesoamerica.
AB  - OBJECTIVE: Telomere length is a biomarker of cumulative stress and inflammation
      related to chronic disease risk. We examined the associations of leukocyte
      telomere length (LTL) with sociodemographic and anthropometric variables and
      estimated LTL family aggregation in Central America, a region with a high burden
      of chronic disease where LTL has not been studied. METHODS: We conducted a cross
      sectional study of 174 school age children and their parents in the capital
      cities of Belize, Honduras, Nicaragua, Costa Rica, Panama, and the city of Tuxtla
      Gutierrez in Mexico. We measured LTL by quantitative PCR in DNA extracted from
      whole blood. We compared the distribution of LTL by categories of
      sociodemographic and anthropometric characteristics using linear regression.
      Family aggregation was estimated with correlation coefficients and intraclass
      correlations. RESULTS: In mothers, LTL was inversely associated with age (P,
      trend < .0001) and positively associated with height (P = .0002). Among fathers,
      LTL was inversely associated with food insecurity (P, trend = .0004). In
      children, boys had 0.10 log units shorter LTL than girls (95% CI: -0.17, -0.03; P
      = .004). LTL was inversely associated with parental education (P, trend = .01)
      and positively associated with paternal age at birth (P, trend < .0001), maternal
      LTL (P, trend = .007), and paternal LTL (P, trend = .02). LTL varied
      significantly by country of origin among all family members. Aggregation was
      greatest between children and their mothers, and mostly occurred at the country,
      rather than family, level. CONCLUSION: LTL is associated with age and height in
      women; food insecurity in men; and sex, parental education, parental LTL, and
      paternal age at birth among children.

PMID- 27891761
TI  - Agroecological management of a soil-dwelling orthopteran pest in vineyards.
AB  - The efficacy of different combinations of undervine and inter-row treatments for
      managing a soil-dwelling orthopteran pest, weta (Hemiandrus sp.), in vineyards
      was investigated over 2 seasons. This insect damages vine buds, thus reducing
      subsequent grape yield. The undervine treatments comprised pea straw mulch,
      mussel shells, tick beans [Vicia faba Linn. var minor (Fab)], plastic sleeves on
      vine trunks (treated control) and control (no intervention), while inter-rows
      contained either the existing vegetation or tick beans. Treatments were arranged
      in a randomized complete block design with 10 replicates. Data were collected on
      weta densities, damage to beans and components of yield. The latter were numbers
      of bud laid down per vine, shoots per bud, clusters per shoot, grape bunches per
      vine, bunch weight and yield. The undervine treatments significantly affected all
      variables except the number of shoots per bud. In contrast, none of the variables
      was significantly affected by the inter-row treatments or their interaction with
      undervine treatments, apart from weta density. At the end of the experiment, weta
      density in the shell treatment was about 58% lower than in the control. As a
      result, there was about 39% significant yield increase in that treatment compared
      to the control. Although the undervine beans and sleeves treatments increased
      yield, there were no reductions in weta density. With undervine beans, the insect
      fed on the bean plants instead of vine buds. Thus, yield in that treatment was
      approximately 28% higher than in the control. These results demonstrate that
      simple agroecological management approaches can reduce above-ground damage by
      soil-dwelling insects.

PMID- 27891760
TI  - Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric
      cancer.
AB  - The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is
      extremely poor. Thus, there is an urgent need to elucidate the molecular
      mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic
      targets. Although previous studies using whole-exome and whole-genome sequencing
      have elucidated genomic alterations in gastric cancer, none has focused on
      comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in
      Type IV, we performed whole-exome sequencing and genome-wide copy number analysis
      on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in
      protein-coding sequences or at splice sites. Among the mutations, we found a
      mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause
      molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins,
      which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV
      samples to investigate the frequency of MRAS mutation. There were eight
      nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is
      recurrently mutated in Type IV. Copy number analysis identified six focal
      amplifications and one homozygous deletion, including insulin-like growth factor
      1 receptor (IGF1R) amplification. The samples with IGF1R amplification had
      remarkably higher IGF1R mRNA and protein expression levels compared with the
      other samples. This is the first report of MRAS recurrent mutation in human tumor
      samples. Our results suggest that MRAS mutation and IGF1R amplification could
      drive tumorigenesis of Type IV and could be new therapeutic targets.

PMID- 27891762
TI  - Judicial Reliance on Parental IQ in Appellate-Level Child Welfare Cases Involving
      Parents with Intellectual and Developmental Disabilities.
AB  - BACKGROUND: Parents with intellectual and developmental disabilities (IDDs) are
      over-represented in child welfare cases. Although IQ per se is an invalid
      indicator of parenting abilities, this study examined the prevalence of judicial
      consideration of parental IQ test evidence in US appellate cases. METHODS: The
      present authors conducted Boolean searches of Westlaw Corporation's case database
      since 1999. The present authors used a six-question checklist to survey the 42
      most recent American appellate cases involving termination of parental rights
      (TPR) decisions that included evidence of parental intellectual and developmental
      disabilities based on IQ. RESULTS: In 86% of cases, parental low IQ was presented
      as a barrier to parenting competence. Higher courts uphold TPR decision in 81% of
      cases involving parents with intellectual and developmental disabilities.
      CONCLUSIONS: Parental IQ scores are routinely relied upon to judge parenting
      capacity in custody cases where parents have intellectual and developmental
      disabilities. The present authors recommend more comprehensive assessments
      examining a broader range of contextual variable that may impact on parenting
      abilities.

PMID- 27891763
TI  - Silver nanoclusters stabilized with denatured fish sperm DNA and the application
      on trace mercury ions detection.
AB  - In this study, fluorescent silver nanoclusters (Ag NCs) were synthesized using
      denatured fish sperm DNA as the template. In contrast to other methods, this
      method did not use artificial DNA as the template. After their reaction with
      denatured fish sperm DNA, Ag+ ions were reduced by NaBH4 to form Ag NCs. The Ag
      NCs showed a strong fluorescence emission at 650 nm when excited at 585 nm. The
      fluorescence intensity increased fourfold at pH 3.78, controlled with Britton
      Robinson buffer solution. The fluorescence of the Ag NCs was quenched in the
      presence of trace mercury ions (Hg2+ ) in a weakly acidic medium and nitrogen
      atmosphere. The extent of the fluorescence quenching of Ag NCs strongly depends
      on the Hg2+ ion concentration over a linear range from 2.0 nmol L-1 to 3.0 MUmol
      L-1 . The detection limit (3sigma/k) for Hg2+ was 0.7 nmol L-1 . Thus, a
      sensitive and rapid method was developed for the detection of Hg2+ ions.

PMID- 27891764
TI  - The recovery paradigm and distress conceptualized as personality disorder: Lack
      of evidence does not equate to a lack of importance.

PMID- 27891765
TI  - HLA-B*13:95, a novel variant of HLA-B*13, discovered in a Taiwanese blood donor.
AB  - A single nucleotide replacement at residue 430 of HLA-B*13:01:01 results in a new
      allele, HLA-B*13:95.

PMID- 27891767
TI  - Terrae Rarae Award: P. C. Junk and P. W. Roesky / Bau Family Award: H. Xu.

PMID- 27891766
TI  - A novel recurrent LIS1 splice site mutation in classic lissencephaly.

PMID- 27891768
TI  - Hyperuricaemia and risk of nonalcoholic fatty liver disease: A meta-analysis.
AB  - BACKGROUND: The association between hyperuricaemia and nonalcoholic fatty liver
      disease (NAFLD), one of the leading causes of cirrhosis worldwide, has been
      demonstrated in recent epidemiological studies. This meta-analysis was conducted
      to summarize all available data and to estimate the risk of NAFLD among subjects
      with hyperuricaemia. METHODS: Comprehensive literature review was conducted using
      MEDLINE and EMBASE database through August 2016 to identify studies that compared
      the risk of NAFLD among subjects with hyperuricaemia vs those with normal uric
      acid level. Effect estimates from individual study were extracted and combined
      together using random-effect, generic inverse variance method of DerSimonian and
      Laird. RESULTS: Twenty-five studies met the eligibility criteria and were
      included in the meta-analysis. The risk of NAFLD in subjects with hyperuricaemia
      was significantly higher than subjects with normal uric acid level with the
      pooled odds ratio (OR) of 1.97 (95% confidence interval (CI), 1.69-2.29). The
      heterogeneity between studies of the overall analysis was high with an I2 of 87%.
      Subgroup analysis based on 11 studies that provided data on males subgroup and
      nine studies that provided data on females subgroup showed that the risk was
      significantly increased for both sexes with pooled OR of 1.64 (95% CI, 1.40-1.93)
      among males and pooled OR of 2.21 (95% CI, 1.85-2.64) among females. CONCLUSIONS:
      A significantly increased risk of NAFLD among patients with hyperuricaemia was
      demonstrated in this meta-analysis. Further studies are required to establish the
      role of uric acid in the pathogenesis of NAFLD.

PMID- 27891769
TI  - Exenatide induces an increase in vasodilatory and a decrease in vasoconstrictive
      mediators.
AB  - In view of the known vasodilatory effects of glucagon-like peptide-1 and
      exenatide, we investigated the effects of exenatide on vasoactive factors. We
      analysed blood samples and mononuclear cells (MNCs) from a previous study,
      collected after a single dose and 12 weeks of exenatide or placebo treatment in a
      series of 24 patients with type 2 diabetes mellitus. After exenatide treatment,
      plasma concentrations of atrial natriuretic peptide, cyclic guanyl monophosphate
      (cGMP) and cyclic adenyl monophosphate increased significantly at 12 weeks.
      Plasma cGMP and adenylate cyclase expression in MNCs increased significantly
      after a single dose. Angiotensinogen concentration fell significantly 2 hours
      after a single dose and at 12 weeks, while renin and angiotensin II levels fell
      significantly only after a single dose and not after 12 weeks of treatment.
      Exenatide also suppressed the plasma concentration of transforming growth factor
      beta and the expression of P311 in MNCs at 12 weeks. Thus, exenatide induces an
      increase in a series of vasodilators, while suppressing the renin-angiotensin
      system. These changes may contribute to the overall vasodilatory effect of
      exenatide.

PMID- 27891771
TI  - Simultaneous determination of trimethylamine and trimethylamine N-oxide in mouse
      plasma samples by hydrophilic interaction liquid chromatography coupled to tandem
      mass spectrometry.
AB  - A method was developed that applies hydrophilic interaction liquid chromatography
      with tandem mass spectrometry in the multiple reaction monitoring mode to
      separate and accurately quantify trimethylamine and trimethylamine N-oxide in a
      single chromatographic run. This was achieved by converting trimethylamine to
      ethyl betaine, which is less volatile and hence results in greatly improved
      quantitation. Ethyl betaine also gives a similar response to trimethylamine N
      oxide using positive-ion electrospray ionization mass spectrometry. It is readily
      separated from trimethylamine N-oxide by hydrophilic liquid chromatography in a 5
      min run and with improved peak shape compared to underivatized trimethylamine.
      Validation of the method yielded a limit of detection (S/N >= 3) of 0.5 ng/mL for
      trimethylamine and 0.25 ng/mL for trimethylamine N-oxide. Method accuracies of
      91.4-105.3% with precisions of 0.4-5.5% were obtained for standard mixtures over
      the range of 2.5-500 ng/mL. Recoveries measured for the extraction of
      trimethylamine and trimethylamine N-oxide spikes into mouse plasma were both
      >90%. The method, which simultaneously measures trimethylamine and trimethylamine
      N-oxide, was successfully applied to mouse plasma samples and could be adapted
      for use with other biological fluids.

PMID- 27891770
TI  - Phenomenological vs. biophysical models of thermal stress in aquatic eggs.
AB  - Predicting species responses to climate change is a central challenge in ecology.
      These predictions are often based on lab-derived phenomenological relationships
      between temperature and fitness metrics. We tested one of these relationships
      using the embryonic stage of a Chinook salmon population. We parameterised the
      model with laboratory data, applied it to predict survival in the field, and
      found that it significantly underestimated field-derived estimates of thermal
      mortality. We used a biophysical model based on mass transfer theory to show that
      the discrepancy was due to the differences in water flow velocities between the
      lab and the field. This mechanistic approach provides testable predictions for
      how the thermal tolerance of embryos depends on egg size and flow velocity of the
      surrounding water. We found support for these predictions across more than 180
      fish species, suggesting that flow and temperature mediated oxygen limitation is
      a general mechanism underlying the thermal tolerance of embryos.

PMID- 27891772
TI  - Twoplex 12/13 C6 aniline stable isotope and linkage-specific sialic acid labeling
      2D-LC-MS workflow for quantitative N-glycomics.
AB  - Quantitative glycomics represents an actively expanding research field ranging
      from the discovery of disease-associated glycan alterations to the quantitative
      characterization of N-glycans on therapeutic proteins. Commonly used analytical
      platforms for comparative relative quantitation of complex glycan samples include
      MALDI-TOF-MS or chromatographic glycan profiling with subsequent data alignment
      and statistical evaluation. Limitations of such approaches include run-to-run
      technical variation and the potential introduction of subjectivity during data
      processing. Here, we introduce an offline 2D LC-MSE workflow for the
      fractionation and relative quantitation of twoplex isotopically labeled N-linked
      oligosaccharides using neutral 12 C6 and 13 C6 aniline (Deltamass = 6 Da).
      Additional linkage-specific derivatization of sialic acids using 4-(4,6-dimethoxy
      1,3,5-trizain-2-yl)-4-methylmorpholinium chloride offered simultaneous and
      advanced in-depth structural characterization. The potential of the method was
      demonstrated for the differential analysis of structurally defined N-glycans
      released from serum proteins of patients diagnosed with various stages of
      colorectal cancer. The described twoplex 12 C6 /13 C6 aniline 2D LC-MS platform
      is ideally suited for differential glycomic analysis of structurally complex N
      glycan pools due to combination and analysis of samples in a single LC-MS
      injection and the associated minimization in technical variation.

PMID- 27891773
TI  - Cigarette smoke alters the secretome of lung epithelial cells.
AB  - Cigarette smoke is the most relevant risk factor for the development of lung
      cancer and chronic obstructive pulmonary disease. Many of its more than 4500
      chemicals are highly reactive, thereby altering protein structure and function.
      Here, we used subcellular fractionation coupled to label-free quantitative MS to
      globally assess alterations in the proteome of different compartments of lung
      epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of
      the human alveolar derived cell line A549 revealed the most pronounced changes
      within the cellular secretome with preferential downregulation of proteins
      involved in wound healing and extracellular matrix organization. In particular,
      secretion of secreted protein acidic and rich in cysteine, a matricellular
      protein that functions in tissue response to injury, was consistently diminished
      by cigarette smoke extract in various pulmonary epithelial cell lines and primary
      cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures.
      Our study reveals a previously unrecognized acute response of lung epithelial
      cells to cigarette smoke that includes altered secretion of proteins involved in
      extracellular matrix organization and wound healing. This may contribute to
      sustained alterations in tissue remodeling as observed in lung cancer and chronic
      obstructive pulmonary disease.

PMID- 27891774
TI  - Does chemical preconditioning contribute to the effectiveness of scaling and root
      planing? An in vitro pilot investigation.
AB  - OBJECTIVES: A solution based on hypochlorite and amino acids was introduced to
      improve cleaning efficacy on the root surfaces. The purpose of this in vitro
      pilot study was to evaluate the time reduction and number of strokes required to
      clean untreated root surfaces in vitro. METHODS: Sixty extracted human teeth
      displaying areas with subgingival calculus were assigned equally to one of three
      treatment groups (n = 20) according to the size of occupied areas, estimated by
      the number of pixels. The groups were assigned to either 30 s penetration time
      (I) or 300 s (II) or no pretreatment application (III). The weight for
      instrumentation was calibrated for a M25A curette (Deppeler/Switzerland) with 500
      g. A new set of tools was used for each group, and each instrument was sharpened
      after single use by an EasySharp Device (Deppeler/Switzerland). RESULTS: The time
      (in seconds) for instrumentation was recorded as follows: Group I: 32/23.5/50
      (median/first quartile/third quartile); group II: 33/20/52.5; group III:
      46.5/35.5/52.3. The results for the numbers of strokes were: Group I: 18/14.3/28;
      group II: 18.5/13/30.5; group III: 17.5/15/25. No statistically significant
      differences (P < 0.05) were found between the three groups for the variables
      'time' and 'number of strokes'. CONCLUSIONS: Within the limits of this in vitro
      pilot study, preconditioning of the calculus on root surfaces with an alkaline
      solution failed to reduce the number of strokes and time of instrumentation
      significantly.

PMID- 27891775
TI  - Surveillance of ventricular septal defects in Delaware.
AB  - BACKGROUND: The prevalence of ventricular septal defects (VSDs), a birth defect
      in which there is an opening in the wall that separates the left and right
      ventricles of the heart, seemed to be substantially higher in Delaware compared
      with the National Birth Defects Prevention Network (NBDPN). The Delaware Birth
      Defects Registry (BDR) noted their high prevalence of VSDs in comparison with
      other states. METHODS: A subset of children with a VSD born in 2007 through 2010
      was identified from the complete reportable statewide defect list that the BDR
      creates each year. VSDs were categorized by type of VSD (muscular,
      perimembranous, conotruncal, or atrioventricular septal defect), by either
      isolated or complex, and then by spontaneously closed, surgically closed, open
      but clinically insignificant, lost to follow-up, fetal or neonatal death.
      RESULTS: The BDR team found a prevalence of VSD of 83.4 per 10,000 including
      fetal/neonatal deaths. Excluding fetal and neonatal deaths the prevalence was
      78.7 per 10,000 live births. Excluding small muscular VSDs, the prevalence in
      Delaware falls to 25.7 per 10,000. CONCLUSION: The BDR team chose to include all
      babies with all types of VSDs. Using these criteria Delaware's prevalence of 78.7
      was higher than that reported by other states (whose prevalence ranges from 1.6
      to 70.0 per 10,000 live births) (National Birth Defects Prevention Network, ).
      Delaware's prevalence is similar to other states when small muscular VSDs are
      excluded. Birth Defects Research (Part A) 106:888-893, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27891776
TI  - Editorial advances in population-based birth defects surveillance, epidemiology,
      and public health practice.

PMID- 27891778
TI  - Paternal and joint parental occupational pesticide exposure and spina bifida in
      the National Birth Defects Prevention Study, 1997 to 2002.
AB  - BACKGROUND: Because of persistent concerns over the association between
      pesticides and spina bifida, we examined the role of paternal and combined
      parental occupational pesticide exposures in spina bifida in offspring using data
      from a large population-based study of birth defects. METHODS: Occupational
      information from fathers of 291 spina bifida cases and 2745 unaffected live born
      control infants with estimated dates of delivery from 1997 to 2002 were collected
      by means of maternal report. Two expert industrial hygienists estimated exposure
      intensity and frequency to insecticides, herbicides, and fungicides.
      Multivariable logistic regression models were used to estimate adjusted odds
      ratios (aOR) and 95% confidence intervals (CI) for exposure to any pesticide and
      to any class of pesticide (yes/no; and by median), and exposure to combinations
      of pesticides (yes/no) and risk of spina bifida. Adjusted odds ratios were also
      estimated by parent exposed to pesticides (neither, mother only, father only,
      both parents). RESULTS: Joint parental occupational pesticide exposure was
      positively associated with spina bifida (aOR, 1.5; 95% CI, 0.9-2.4) when compared
      with infants with neither maternal nor paternal exposures; a similar association
      was not observed when only one parent was exposed. There was a suggested positive
      association between combined paternal insecticide and fungicide exposures and
      spina bifida (aOR, 1.5; 95% CI, 0.8-2.8), however, nearly all other aORs were
      close to unity. CONCLUSION: Overall, there was little evidence paternal
      occupational pesticide exposure was associated with spina bifida. However, the
      small numbers make it difficult to precisely evaluate the role of pesticide
      classes, individually and in combination. Birth Defects Research (Part A) 106:963
      971, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27891777
TI  - Maternal autoimmune disease and birth defects in the National Birth Defects
      Prevention Study.
AB  - BACKGROUND: Little is known about the association between maternal autoimmune
      disease or its treatment and the risk of birth defects. We examined these
      associations using data from the National Birth Defects Prevention Study, a multi
      site, population-based, case-control study. METHODS: Analyses included 25,116
      case and 9897 unaffected control infants with estimated delivery dates between
      1997 and 2009. Information on autoimmune disease, medication use, and other
      pregnancy exposures was collected by means of telephone interview. Adjusted odds
      ratios (ORs) and 95% confidence intervals (CIs) were estimated for birth defects
      with five or more exposed cases; crude ORs and exact 95% CIs were estimated for
      birth defects with three to four exposed cases. RESULTS: Autoimmune disease was
      reported by 373 mothers (279 case and 94 control mothers). The majority of birth
      defects evaluated were not associated with autoimmune disease; however, a
      statistically significant association between maternal autoimmune disease and
      encephalocele was observed (OR, 4.64; 95% CI, 1.95-11.04). Eighty-two mothers
      with autoimmune disease used an immune modifying/suppressing medication during
      pregnancy; this was associated with encephalocele (OR, 7.26; 95% CI, 1.37-24.61)
      and atrial septal defects (OR, 3.01; 95% CI, 1.16-7.80). CONCLUSION: Our findings
      suggest maternal autoimmune disease and treatment are not associated with the
      majority of birth defects, but may be associated with some defects, particularly
      encephalocele. Given the low prevalence of individual autoimmune diseases and the
      rare use of specific medications, we were unable to examine associations of
      specific autoimmune diseases and medications with birth defects. Other studies
      are needed to confirm these findings. Birth Defects Research (Part A) 106:950
      962, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27891780
TI  - ICD-10-based expanded code set for use in cleft lip/palate research and
      surveillance.
AB  - BACKGROUND: On October 1, 2015, the United States required use of the Clinical
      Modification of the International Classification of Diseases, 10th Revision (ICD
      10-CM) for diagnostic coding. The ICD-10-CM code set is limited to gross
      categories for cleft lip and/or cleft palate (using only four of a possible seven
      characters). METHODS: Herein, a clinically useful expansion of the ICD-10-CM code
      set is proposed to improve the diagnostic accuracy necessary for individual
      clinical, research, and statistical projects that require it. (This is similar to
      how the Centers for Disease Control and Prevention/British Paediatric Association
      Code served to extend the ICD-9 code base.) RESULTS: Our proposed expansion does
      not replace the required use of ICD-10-CM for clinical, administrative, or
      financial transactions. Rather, it is offered as an optional set of cleft codes
      that could be used in parallel to document true classification-level data with
      phenotypic accuracy. CONCLUSION: The expanded set is "collapsible" into the
      official ICD-10-CM codes; this improves compatibility of the expanded codes that
      would be contained in research and epidemiologic databases with the standard
      codes from hospital electronic medical record systems and administrative billing
      data. Birth Defects Research (Part A) 106:905-914, 2016. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27891779
TI  - Using insurance claims data to identify and estimate critical periods in
      pregnancy: An application to antidepressants.
AB  - BACKGROUND: Health insurance claims are a rich data source to examine medication
      use in pregnancy. Our objective was to identify pregnant women, their pregnancy
      outcomes, and date of their last menstrual period (LMP), and to estimate
      antidepressant dispensations in pregnancy. METHODS: From a literature search, we
      identified diagnosis and procedure codes indicating the end of a pregnancy. Using
      Truven Health MarketScan(r) Commercial Claims and Encounters Databases, we
      identified all inpatient admissions and outpatient service claims with these
      codes. We developed an algorithm to assign: (1) pregnancy outcome (ectopic
      pregnancy, induced or spontaneous abortion, live birth, or stillbirth), and (2)
      estimated gestational age, to each inpatient or outpatient visit. For each
      pregnancy outcome, we estimated the LMP as the admission (for inpatient visits)
      or service (for outpatient visits) date minus the gestational age. To
      differentiate visits associated with separate pregnancies, we required >= 2
      months between one pregnancy outcomes and the LMP of the next pregnancy. We used
      this algorithm to identify pregnancies in 2013 and to estimate the proportion of
      women who filled a prescription for an antidepressant from an outpatient pharmacy
      at various time points in pregnancy. RESULTS: We identified 488,887 pregnancies
      in 2013; 79% resulted in a live birth. A prescription for an antidepressant was
      filled in 6.2% of pregnancies. Dispensations varied throughout pregnancy and were
      lowest (3.1%) during the second trimester. CONCLUSION: This work will inform
      future efforts to estimate medication dispensations during critical periods of
      preconception, interconception, and pregnancy using health insurance claims data.
      Birth Defects Research (Part A) 106:927-934, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27891781
TI  - Geographic distribution of live births with tetralogy of Fallot in North Carolina
      2003 to 2012.
AB  - BACKGROUND: Geographic variation in congenital heart disease is not well
      described. This study uses geographic information systems (GIS) to describe the
      spatial epidemiology of tetralogy of Fallot (TOF), in North Carolina (NC) and to
      compare travel time for cases to congenital heart centers in NC. METHODS: Using
      the NC Birth Defects Monitoring Program database, live births with TOF born
      between 2003 and 2012 were identified. Birth certificates provided demographic
      variables. A denominator of live births/zip code was obtained from the NC live
      births database. ArcGIS(r) software was used to illustrate TOF prevalence by zip
      code, and SatScanTM was used to identify spatial clusters of TOF cases and to
      identify changes in cluster location over time. Driving time to each of five NC
      congenital heart centers was predicted based on road systems information.
      RESULTS: A total of 496 infants were born with TOF between 2003 and 2012. The
      prevalence was 4.2/10,000 live births. A large cluster (330 zip codes, 306 cases)
      was identified in northeastern NC. Average driving time for each case to closest
      congenital heart center was: University of North Carolina 37 min, Vident Medical
      Center 64 min, Duke University 58 min, Carolina's Medical Center 89 min, and Wake
      Forest Baptist Health 57 min. Overall, average predicted driving time to the
      nearest congenital heart center was 61 min. CONCLUSION: Approximately 50
      infants/year were born with TOF in NC. One cluster was identified. Further study
      is necessary to explore potential explanations for the observed case cluster. As
      interest in regionalization of congenital heart surgery grows, GIS and spatial
      analysis can become increasingly useful tools for health care planning. Birth
      Defects Research (Part A) 106:881-887, 2016. (c) 2016 Wiley Periodicals, Inc.

PMID- 27891782
TI  - Using state and provincial surveillance programs to reduce risk of recurrence of
      neural tube defects in the United States and Canada: A missed opportunity?
AB  - BACKGROUND: Once a woman has had a fetus or infant affected with a neural tube
      defect (NTD), the risk of recurrence is approximately 3%. This risk can be
      significantly reduced by folic acid supplement consumption during the
      periconceptional period; however, this requires women at risk to be adequately
      informed about the appropriate dosage and timing of supplement intake before
      planning another pregnancy. As birth defects surveillance programs are tasked
      with identifying and documenting NTD-affected pregnancies and births, they are in
      a unique position to support recurrence prevention activities. METHODS: In 2015,
      we surveyed state and provincial birth defects surveillance programs to assess
      their NTD recurrence prevention activities. The online survey was sent to
      programs in 52 United States (U.S.) jurisdictions and all 13 provinces and
      territories in Canada. Findings were compared with a similar survey conducted in
      2005 among U.S. programs. RESULTS: In 2015, of the 44 U.S. and Canadian
      surveillance programs that responded, only 9 programs (7 U.S. and 2 Canadian)
      reported currently having activities specifically directed toward preventing NTD
      recurrence. Compared with a 2005 survey of U.S. programs, the number of U.S.
      programs working on NTD recurrence prevention decreased by almost 50% (from 13 to
      7 programs). CONCLUSION: The number of birth defects surveillance programs with
      NTD recurrence prevention activities has decreased over the past decade due to a
      range of barriers, most notably a lack of resources. However, while some
      recurrence prevention activities require part-time staff, other activities could
      be accomplished using minimal resources. Birth Defects Research (Part A) 106:875
      880, 2016.(c) 2016 Wiley Periodicals, Inc.

PMID- 27891784
TI  - Characterizing facial features in individuals with craniofacial microsomia: A
      systematic approach for clinical research.
AB  - BACKGROUND: Craniofacial microsomia (CFM) is a congenital condition with wide
      phenotypic variability, including hypoplasia of the mandible and external ear. We
      assembled a cohort of children with facial features within the CFM spectrum and
      children without known craniofacial anomalies. We sought to develop a
      standardized approach to assess and describe the facial characteristics of the
      study cohort, using multiple sources of information gathered over the course of
      this longitudinal study and to create case subgroups with shared phenotypic
      features. METHODS: Participants were enrolled between 1996 and 2002. We
      classified the facial phenotype from photographs, ratings using a modified
      version of the Orbital, Ear, Mandible, Nerve, Soft tissue (OMENS) pictorial
      system, data from medical record abstraction, and health history questionnaires.
      RESULTS: The participant sample included 142 cases and 290 controls. The average
      age was 13.5 years (standard deviation, 1.3 years; range, 11.1-17.1 years). Sixty
      one percent of cases were male, 74% were white non-Hispanic. Among cases, the
      most common features were microtia (66%) and mandibular hypoplasia (50%). Case
      subgroups with meaningful group definitions included: (1) microtia without other
      CFM-related features (n = 24), (2) microtia with mandibular hypoplasia (n = 46),
      (3) other combinations of CFM- related facial features (n = 51), and (4) atypical
      features (n = 21). CONCLUSION: We developed a standardized approach for
      integrating multiple data sources to phenotype individuals with CFM, and created
      subgroups based on clinically-meaningful, shared characteristics. We hope that
      this system can be used to explore associations between phenotype and clinical
      outcomes of children with CFM and to identify the etiology of CFM. Birth Defects
      Research (Part A) 106:915-926, 2016.(c) 2016 Wiley Periodicals, Inc.

PMID- 27891783
TI  - Population-based microcephaly surveillance in the United States, 2009 to 2013: An
      analysis of potential sources of variation.
AB  - BACKGROUND: Congenital microcephaly has been linked to maternal Zika virus
      infection. However, ascertaining infants diagnosed with microcephaly can be
      challenging. METHODS: Thirty birth defects surveillance programs provided data on
      infants diagnosed with microcephaly born 2009 to 2013. The pooled prevalence of
      microcephaly per 10,000 live births was estimated overall and by maternal/infant
      characteristics. Variation in prevalence was examined across case finding
      methods. Nine programs provided data on head circumference and conditions
      potentially contributing to microcephaly. RESULTS: The pooled prevalence of
      microcephaly was 8.7 per 10,000 live births. Median prevalence (per 10,000 live
      births) was similar among programs using active (6.7) and passive (6.6) methods;
      the interdecile range of prevalence estimates was wider among programs using
      passive methods for all race/ethnicity categories except Hispanic. Prevalence
      (per 10,000 live births) was lowest among non-Hispanic Whites (6.5) and highest
      among non-Hispanic Blacks and Hispanics (11.2 and 11.9, respectively); estimates
      followed a U-shaped distribution by maternal age with the highest prevalence
      among mothers <20 years (11.5) and >=40 years (13.2). For gestational age and
      birth weight, the highest prevalence was among infants <32 weeks gestation and
      infants <1500 gm. Case definitions varied; 41.8% of cases had an HC >= the 10th
      percentile for sex and gestational age. CONCLUSION: Differences in methods,
      population distribution of maternal/infant characteristics, and case definitions
      for microcephaly can contribute to the wide range of observed prevalence
      estimates across individual birth defects surveillance programs. Addressing these
      factors in the setting of Zika virus infection can improve the quality of
      prevalence estimates. Birth Defects Research (Part A) 106:972-982, 2016. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27891785
TI  - Editorial brain malformation surveillance in the Zika era.
AB  - The current surveillance systems for congenital microcephaly are necessary to
      monitor the impact of Zika virus (ZIKV) on the developing human brain, as well as
      the ZIKV prevention efforts. However, these congenital microcephaly surveillance
      systems are insufficient. Abnormalities of neuronal differentiation, development
      and migration may occur among infants with normal head circumference who have
      intrauterine exposure to ZIKV. Therefore, surveillance for congenital
      microcephaly does not ascertain many of the infants seriously impacted by
      congenital ZIKV infection. Furthermore, many infants with normal head
      circumference and with malformations of the brain cortex do not have clinical
      manifestations of their congenital malformations until several months to many
      years after birth, when they present with clinical manifestations such as
      seizures/epilepsy, developmental delays with or without developmental regression,
      and/or motor impairment. In response to the ZIKV threat, public health
      surveillance systems must be enhanced to ascertain a wide variety of congenital
      brain malformations, as well as their clinical manifestations that lead to
      diagnostic brain imaging. Birth Defects Research (Part A) 106:869-874, 2016. (c)
      2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology
      Published by Wiley Periodicals, Inc.

PMID- 27891786
TI  - A quality assessment of reporting sources for microcephaly in Utah, 2003 to 2013.
AB  - BACKGROUND: Obtaining accurate microcephaly prevalence is important given the
      recent association between microcephaly and Zika virus. Assessing the quality of
      data sources can guide surveillance programs as they focus their data collection
      efforts. The Utah Birth Defect Network (UBDN) has monitored microcephaly by data
      sources since 2003. The objective of this study was to examine the impact of
      reporting sources for microcephaly surveillance. METHODS: All reported cases of
      microcephaly among Utah mothers from 2003 to 2013 were clinically reviewed and
      confirmed. The UBDN database was linked to state vital records and hospital
      discharge data for analysis. Reporting sources were analyzed for positive
      predictive value and sensitivity. RESULTS: Of the 477 reported cases of
      microcephaly, 251 (52.6%) were confirmed as true cases. The UBDN identified 94
      additional cases that were reported to the surveillance system as another birth
      defect, but were ultimately determined to be true microcephaly cases. The
      prevalence for microcephaly based on the UBDN medical record abstraction and
      clinical review was 8.2 per 10,000 live births. Data sources varied in the number
      and accuracy of reporting, but a case was more likely to be a true case if
      identified from multiple sources than from a single source. CONCLUSION: While
      some reporting sources are more likely to identify possible and true microcephaly
      cases, maintaining a multiple source methodology allows for more complete case
      ascertainment. Surveillance programs should conduct periodic assessments of data
      sources to ensure their systems are capturing all possible birth defects cases.
      Birth Defects Research (Part A) 106:983-988, 2016. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27891787
TI  - Evaluation of the Western Australian Register of Developmental Anomalies: Thirty
      five years of surveillance.
AB  - BACKGROUND: The birth defects component of the Western Australian Register for
      Developmental Anomalies (WARDA-BD) was evaluated to assess its efficiency,
      effectiveness, and data quality. METHODS: WARDA-BD was evaluated using the
      Centers for Disease Control and Prevention Guidelines for Evaluating Public
      Health Surveillance Systems and Data Quality Standards from the National Birth
      Defects Prevention Network. The evaluation included interviews with Register
      staff, local community organizations, parents, clinicians, and researchers;
      process observation; and secondary data analyses. RESULTS: WARDA-BD is a
      statutory, statewide, population-based surveillance system established in 1980
      that monitors approximately 30,000 births annually. Identification of eligible
      cases is for children up to age 6 years through active and passive ascertainment
      methods from multiple sources including birth, death, and hospitalization data;
      antenatal ultrasonography; hospital unit logs; medical records; fetal medicine
      departments; cytogenetic laboratories; specialty clinics; and pediatric surgery
      and pathology departments. Defect diagnoses are verified and coded using the 5
      digit British Paediatric Association extension of the International
      Classification of Disease, Ninth Revision system. Register staff monitor Register
      data for completeness and accuracy resulting in high quality data with a low
      percentage of missing items. CONCLUSION: Strengths of WARDA-BD include high data
      quality, timeliness, representativeness, stable funding, active community
      engagement, and high staff retention. Its data were used in numerous
      epidemiologic investigations resulting in >325 peer-reviewed publications.
      Potential weaknesses include the limited number of variables collected and low
      visibility. Although WARDA-BD uses labor intensive case ascertainment and quality
      assurance and control processes, the Register provides accurate and essential
      data for stakeholders. Birth Defects Research (Part A) 106:894-904, 2016. (c)
      2016 Wiley Periodicals, Inc.

PMID- 27891789
TI  - Incorrect Panel in Figure 3 of the Article by Ellman et al (Arthritis Rheum, June
      2012).

PMID- 27891790
TI  - Clinical Connections.

PMID- 27891788
TI  - Association between antibiotic use among pregnant women with urinary tract
      infections in the first trimester and birth defects, National Birth Defects
      Prevention Study 1997 to 2011.
AB  - BACKGROUND: Previous studies noted associations between birth defects and some
      antibiotics (e.g., nitrofurantoin, sulfonamides) but not others (e.g.,
      penicillins). It is unclear if previous findings were due to antibiotic use,
      infections, or chance. To control for potential confounding by indication, we
      examined associations between antibiotic use and birth defects, among women
      reporting urinary tract infections (UTIs). METHODS: The National Birth Defects
      Prevention Study is a multi-site, population-based case-control study. Case
      infants/fetuses have any of over 30 major birth defects and controls are live
      born infants without major birth defects. We analyzed pregnancies from 1997 to
      2011 to estimate the association between maternally reported periconceptional
      (month before conception through the third month of pregnancy) use of
      nitrofurantoin, trimethoprim-sulfamethoxazole, or cephalosporins and specific
      birth defects, among women with periconceptional UTIs. Women with
      periconceptional UTIs who reported penicillin use served as the comparator.
      RESULTS: Periconceptional UTIs were reported by 7.8% (2029/26,068) of case and
      6.7% (686/10,198) of control mothers. Most (68.2% of case, 66.6% of control
      mothers) also reported antibiotic use. Among 608 case and 231 control mothers
      reporting at least one periconceptional UTI and certain antibiotic use, compared
      with penicillin, nitrofurantoin use was associated with oral clefts in the
      offspring (adjusted odds ratio, 1.97 [95% confidence interval, 1.10-3.53]),
      trimethoprim-sulfamethoxazole use with esophageal atresia (5.31 [1.39-20.24]) and
      diaphragmatic hernia (5.09 [1.20-21.69]), and cephalosporin use with anorectal
      atresia/stenosis (5.01 [1.34-18.76]). CONCLUSION: Periconceptional exposure to
      some antibiotics might increase the risk for certain birth defects. However,
      because individual birth defects are rare, absolute risks should drive treatment
      decisions.Birth Defects Research (Part A) 106:940-949, 2016.(c) 2016 Wiley
      Periodicals, Inc.

PMID- 27891795
TI  - Erratum.

PMID- 27891794
TI  - Re: Does the Epi-No birth trainer prevent vaginal birthrelatedpelvic floor
      trauma? A multicentre prospective randomised controlled trial: The Epi-No birth
      trainer makes it easier to accomplish 100% intact perineums at vaginal birth,
      where this is a goal.

PMID- 27891796
TI  - Authors' reply re: Cost-effectiveness of a pro-active approach of urinary
      incontinence in women.

PMID- 27891797
TI  - The aetiology of pre-eclampsia, 1945-1953.

PMID- 27891798
TI  - Authors' reply re: Clinical pharmacokinetic properties of magnesium sulphate in
      women with pre-eclampsia and eclampsia: a systematic review.

PMID- 27891799
TI  - A report from #BlueJC: How to compare quality and safety of surgery for cancer?

PMID- 27891801
TI  - Leiomyosarcoma and myomectomy: is the cat ever in the bag?

PMID- 27891803
TI  - Editor's reply re: Does the Epi-No birth trainer prevent vaginal birth-related
      pelvic floor trauma? A multicenter prospective randomised controlled trial.

PMID- 27891804
TI  - Re: Cost-effectiveness of a pro-active approach of urinary incontinence in women.

PMID- 27891805
TI  - Re: Comparison of techniques used to deliver a deeply impacted fetal head at full
      dilation: a systematic review and meta-analysis.

PMID- 27891806
TI  - Authors' reply re: Does the Epi-No birth trainer prevent vaginal birth-related
      pelvic floor trauma? A multicenter prospective randomised controlled trial.

PMID- 27891807
TI  - Authors' reply re: Comparison of techniques used to deliver a deeply impacted
      fetal head at full dilation: a systematic review and meta-analysis.

PMID- 27891808
TI  - Authors' reply re: Wide differences in mode of delivery within Europe: risk
      stratified analyses of aggregated routine data from the Euro-Peristat study.

PMID- 27891809
TI  - Re: Clinical pharmacokinetic properties of magnesium sulphate in women with pre
      eclampsia and eclampsia: a systematic review: Clinical pharmacokinetics of low
      dose magnesium sulphate regimens for eclampsia in low-resource countries: does it
      matter?

PMID- 27891810
TI  - Re: Adverse psychological outcomes following colposcopy and related procedures: a
      systematic review: Psychological sequelae of cervical cytology screening: the
      need for continual awareness and pre-emptive steps.

PMID- 27891811
TI  - Re: Wide differences in mode of delivery between countries in Europe: risk
      stratified analyses of aggregated routine data from the Euro-Peristat study:
      Caesarean section rates are the WRONG target.

PMID- 27891812
TI  - Hudson's landmark contribution to ovarian cancer surgery.

PMID- 27891813
TI  - Geographic variation in genetic and demographic performance: new insights from an
      old biogeographical paradigm.
AB  - The 'centre-periphery hypothesis' (CPH) is a long-standing postulate in ecology
      that states that genetic variation and demographic performance of a species
      decrease from the centre to the edge of its geographic range. This hypothesis is
      based on an assumed concordance between geographical peripherality and ecological
      marginality such that environmental conditions become harsher towards the limits
      of a species range. In this way, the CPH sets the stage for understanding the
      causes of distribution limits. To date, no study has examined conjointly the
      consistency of these postulates. In an extensive literature review we discuss the
      birth and development of the CPH and provide an assessment of the CPH by
      reviewing 248 empirical studies in the context of three main themes. First, a
      decrease in species occurrence towards their range limits was observed in 81% of
      studies, while only 51% demonstrated reduced abundance of individuals. A decline
      in genetic variation, increased differentiation among populations and higher
      rates of inbreeding were demonstrated by roughly one in two studies (47, 45 and
      48%, respectively). However, demographic rates, size and population performance
      less often followed CPH expectations (20-30% of studies). We highlight the impact
      of important methodological, taxonomic, and biogeographical biases on such
      validation rates. Second, we found that geographic and ecological marginality
      gradients are not systematically concordant, which casts doubt on the reliability
      of a main assumption of the CPH. Finally, we attempt to disentangle the relative
      contribution of geographical, ecological and historical processes on the spatial
      distribution of genetic and demographic parameters. While ecological marginality
      gradients explain variation in species' demographic performance better than
      geographic gradients, contemporary and historical factors may contribute
      interactively to spatial patterns of genetic variation. We thereby propose a
      framework that integrates species' ecological niche characteristics together with
      current and past range structure to investigate spatial patterns of genetic and
      demographic variation across species ranges.

PMID- 27891814
TI  - Friendships and Intimate Relationships among People with Intellectual
      Disabilities: A Thematic Synthesis.
AB  - BACKGROUND: The purpose of this thematic synthesis was to review qualitative
      studies on perspectives of persons with intellectual disabilities regarding
      friendships and intimate relationships. MATERIALS AND METHODS: A literature
      search was conducted, including studies published between 2004 and 2014,
      involving participants 14 years of age or older, who had intellectual
      disabilities, and participated in focus groups or interviews. RESULTS: Eighteen
      studies were included. Three master themes were identified: (i) How do I know
      someone is my friend? (ii) How do I know someone is my boyfriend or girlfriend?
      and (iii) What helps and hinders relationships? CONCLUSIONS: Understanding how
      people with intellectual disabilities describe relationships, and being aware of
      factors that support and impede relationships, will aid stakeholders in
      developing training, policies, programmes and services. Knowledge translation of
      research that focuses on strategies aimed at supporting relationships is crucial
      to affect change in applied settings and improve quality of life for persons with
      intellectual disabilities.

PMID- 27891815
TI  - Quantitative T1-mapping detects cloudy-enhancing tumor compartments predicting
      outcome of patients with glioblastoma.
AB  - Contrast enhancement of glioblastomas (GBM) is caused by the decrease in
      relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1
      (qT1) discovers a subtle enhancement in GBM patients that is invisible in
      standard MRI. We assessed the volume change of this "cloudy" enhancement during
      radio-chemotherapy and its impact on patients' progression-free survival (PFS).
      We enrolled 18 GBM patients in this observational, prospective cohort study and
      measured 3T-MRI pre- and post contrast agent with standard T1-weighted (T1w) and
      with sequences to quantify T1 before radiation, and at 6-week intervals during
      radio-chemotherapy. We measured contrast enhancement by subtracting pre from post
      contrast contrast images, yielding relative signal increase ?T1w and relative T1
      shortening ?qT1. On ?qT1, we identified a solid and a cloudy-enhancing
      compartment and evaluated the impact of their therapy-related volume change upon
      PFS. In ?qT1 maps cloudy-enhancing compartments were found in all but two
      patients at baseline and in all patients during therapy. The qT1 decrease in the
      cloudy-enhancing compartment post contrast was 21.64% versus 1.96% in the
      contralateral control tissue (P < 0.001). It was located at the margin of solid
      enhancement which was also seen on T1w. In contrast, the cloudy-enhancing
      compartment was visually undetectable on ?T1w. A volume decrease of more than
      21.4% of the cloudy-enhancing compartment at first follow-up predicted longer PFS
      (P = 0.038). Cloudy-enhancing compartment outside the solid contrast-enhancing
      area of GBM is a new observation which is only visually detectable with qT1
      mapping and may represent tumor infiltration. Its early volume decrease predicts
      a longer PFS in GBM patients during standard radio-chemotherapy.

PMID- 27891817
TI  - Preliminary study of personality traits in Chinese lung cancer patients:
      Modification by neurotensin receptor 1 polymorphisms.
AB  - This study recruited 148 lung cancer patients and 157 healthy Chinese individuals
      to evaluate the personality traits of Chinese lung cancer patients using the
      Tridimensional Personality Questionnaire and to investigate the associations
      between these traits and the rs6090453C/G and rs6011914C/G polymorphisms of the
      neurotensin receptor 1 gene. The results demonstrated significant differences in
      the Tridimensional Personality Questionnaire total and subscale scores between
      the 2 groups. Significant differences were found in the reward dependence 2 (RD2)
      score between the rs6090453C/G genotypes and in the total harm avoidance (HA),
      HA1, HA2, HA4, and RD2 scores between the rs6011914C/G genotypes. Thus, patients
      with lung cancer have specific personality traits, and variations in the
      neurotensin receptor 1 gene may be involved in the biological mechanisms of the
      HA and RD personality traits.

PMID- 27891818
TI  - Exploiting Deep Eutectic Solvents and Organolithium Reagent Partnerships:
      Chemoselective Ultrafast Addition to Imines and Quinolines Under Aerobic Ambient
      Temperature Conditions.
AB  - Shattering the long-held dogma that organolithium chemistry needs to be performed
      under inert atmospheres in toxic organic solvents, chemoselective addition of
      organolithium reagents to non-activated imines and quinolines has been
      accomplished in green, biorenewable deep eutectic solvents (DESs) at room
      temperature and in the presence of air, establishing a novel and sustainable
      access to amines. Improving on existing methods, this approach proceeds in the
      absence of additives; occurs without competitive enolization, reduction or
      coupling processes; and reactions were completed in seconds. Comparing RLi
      reactivities in DESs with those observed in pure glycerol or THF suggests a
      kinetic anionic activation of the alkylating reagents occurs, favoring
      nucleophilic addition over competitive hydrolysis.

PMID- 27891816
TI  - DLL4 overexpression increases gastric cancer stem/progenitor cell self-renewal
      ability and correlates with poor clinical outcome via Notch-1 signaling pathway
      activation.
AB  - Gastric cancer is one of the most common malignant diseases, and poses a serious
      threat to the quality of human life. Gastric cancer stem/progenitor cells
      (GCSPCs) have critical effects on tumor formation, affecting specific features of
      self-renewal and differentiation and playing a critical role in metastasis. The
      Notch-1 pathway is crucially important to GCSPCs and is regulated by DLL4. In
      this study, DLL4 and Nestin levels were measured in 383 gastric cancer tissue
      samples by immunohistochemistry, and the clinico-pathological features of
      patients assessed. After DLL4 silencing in selected gastric cancer cell lines,
      the expression of GCSPC markers and colony formation ability were analyzed and
      the self-renewal and differentiation capacities of the cells were evaluated. The
      relationship between DLL4 levels and Notch-1 signaling pathway effector amounts
      was assessed via Western blotting and immunofluorescence. Finally, the tumor
      formation ability of the gastric cancer cells was evaluated with different levels
      of DLL4 and multiple cell densities in vivo. Our results indicate that DLL4
      expression is associated with TNM stage and cancer metastasis, with high amounts
      of DLL4 leading to poor outcome. DLL4 silencing inhibited the self-renewal
      ability of GCSPCs and increased their multidifferentiation capacity, resulting in
      reduced GCSPC ratios. DLL4 knockdown also blocked the Notch-1 pathway, weakening
      invasion ability and resistance to 5-FU chemotherapy. In vivo, DLL4 silencing
      inhibited the tumor formation ability of GCSPCs. In conclusion, DLL4 affects
      GCSPC stemness, altering their pathological behavior. DLL4 silencing inhibits
      GCSPC metastatic potential both in vitro and in vivo by impeding Notch-1
      signaling pathway activation, indicating that DLL4 may be a new potential
      therapeutic target.

PMID- 27891819
TI  - Autism and emotional face-viewing.
AB  - Atypical patterns of face-scanning in individuals with autism spectrum disorder
      (ASD) may contribute to difficulties in social interactions, but there is little
      agreement regarding what exactly characterizes face-viewing in ASD. In addition,
      little research has examined how face-viewing is modulated by the emotional
      expression of the stimuli, in individuals with or without ASD. We used eye
      tracking to explore viewing patterns during perception of dynamic emotional
      facial expressions in relatively large groups of individuals with (n = 57) and
      without ASD (n = 58) and examined diagnostic- and age-related effects, after
      subgrouping children and adolescents (<=18 years), on the one hand, and adults
      (>18 years), on the other. Results showed that children/adolescents with ASD
      fixated the mouth of happy and angry faces less than their typically developing
      (TD) peers, and conversely looked more to the eyes of happy faces. Moreover,
      while all groups fixated the mouth in happy faces more than in other expressions,
      children/adolescents with ASD did relatively less so. Correlation analysis showed
      a similar lack of relative orientation towards the mouth of smiling faces in TD
      children/adolescents with high autistic traits, as measured by the Autism
      Spectrum Quotient (AQ). Among adults, participants with ASD only attended less to
      the eyes for neutral faces. Our study shows that the emotional content of a face
      influences gaze behaviour, and that this effect is not fully developed in
      children/adolescents with ASD. Interestingly, this lack of differentiation
      observed in the younger ASD group was also seen in younger TD individuals with
      higher AQ scores. Autism Res 2017, 10: 901-910. (c) 2016 International Society
      for Autism Research, Wiley Periodicals, Inc.

PMID- 27891820
TI  - Investigating diagnostic bias in autism spectrum conditions: An item response
      theory analysis of sex bias in the AQ-10.
AB  - Diagnostic bias is a concern in autism spectrum conditions (ASC) where prevalence
      and presentation differ by sex. To ensure that females with ASC are not under
      identified, it is important that ASC screening tools do not systematically
      underestimate autistic traits in females relative to males. We evaluated whether
      the AQ-10, a brief screen for ASC recommended by the National Institute of
      Clinical Excellence in cases of suspected ASC, exhibits such a bias. Using an
      item response theory approach, we evaluated differential item functioning and
      differential test functioning. We found that although individual items showed
      some sex bias, these biases at times favored males and at other times favored
      females. Thus, at the level of test scores the item-level biases cancelled out to
      give an unbiased overall score. Results support the continued use of the AQ-10
      sum score in its current form; however, suggest that caution should be exercised
      when interpreting responses to individual items. The nature of the item level
      biases could serve as a guide for future research into how ASC affects males and
      females differently. Autism Res 2017, 10: 790-800. (c) 2016 International Society
      for Autism Research, Wiley Periodicals, Inc.

PMID- 27891821
TI  - Detection of HLA-C*04:247, a novel HLA-C*04 variant, in a Taiwanese hematopoietic
      stem cell donor.
AB  - One nucleotide replacement at residue 511 of the HLA-C*04:01:01:01 results in a
      novel allele, HLA-C*04:247.

PMID- 27891822
TI  - Does radiotherapy still have a role in unresected biliary tract cancer?
AB  - The benefits of radiotherapy for inoperable biliary tract cancer remain unclear
      due to the lack of randomized data. We evaluated the impact of radiotherapy on
      survival in elderly patients using the SEER-Medicare database. Patients in the
      SEER-Medicare database with inoperable biliary tract tumors diagnosed between
      1998 and 2011 were included. We used multivariate logistic regression to evaluate
      factors associated with treatment selection, and multivariate Cox regression and
      propensity score matching to evaluate treatment selection in relation to
      subsequent survival. Of the 2343 patients included, 451 (19%) received
      radiotherapy within 4 months of diagnosis. The use of radiotherapy declined over
      time, and was influenced by receipt of chemotherapy and patient age, race,
      marital status, poverty status, and tumor stage and type. Median survival was 9.3
      (95% CI 8.7-9.7) months among patients who did not receive radiation and 10.0
      (95% CI 9.1-11.3) months among those who received radiation, conditional on
      having survived 4 months. In patients who received chemotherapy (n = 1053),
      receipt of radiation was associated with improved survival, with an adjusted
      hazard ratio of 0.82 (95% 0.70-0.97, P = 0.02). In patients who did not receive
      chemotherapy (n = 1290), receipt of radiation was not associated with improved
      survival, with an adjusted hazard ratio of 1.09 (95% 0.91-1.30, P = 0.34).
      Propensity-scored matched analyses showed similar results. Despite the survival
      benefit associated with the addition of radiotherapy to chemotherapy, the use of
      radiation for unresectable biliary tract cancers has declined over time.

PMID- 27891823
TI  - Marijuana use and inpatient outcomes among hospitalized patients: analysis of the
      nationwide inpatient sample database.
AB  - The purpose of this paper is to examine the relationship between marijuana use
      and health outcomes among hospitalized patients, including those hospitalized
      with a diagnosis of cancer. A total of 387,608 current marijuana users were
      identified based on ICD-9 codes for marijuana use among hospitalized patients in
      the Nationwide Inpatient Sample database between 2007 and 2011. Logistic
      regression analysis was performed to determine the association between marijuana
      use and heart failure, cardiac disease, stroke, and in-hospital mortality. All
      models were adjusted for age, gender, race, residential income, insurance,
      residential region, pain, and number of comorbidities. Among hospitalized
      patients, marijuana use was associated with a 60% increased odds of stroke (OR:
      1.60, 95% CI: 1.44-1.77) compared with non-users, but significantly reduced odds
      of heart failure (OR: 0.78, 95% CI: 0.75-0.82), cardiac disease (OR: 0.86, 95%
      CI: 0.82-0.91), or in-hospital mortality (OR: 0.41, 95% CI: 0.38-0.44). Among
      cancer patients, odds of in-hospital mortality was significantly reduced among
      marijuana users compared with non-users (OR: 0.44, 95% CI: 0.35-0.55).
      Hospitalized marijuana users were more likely to experience a stroke compared
      with non-users, but less likely to experience in-hospital mortality. Prospective
      studies will be needed to better characterize the health effects of marijuana
      use, especially among older, sicker, and/or hospitalized patients. In the
      meantime, conversations regarding marijuana use/misuse may be warranted in the
      clinical setting in order for patients and healthcare providers to adequately
      weigh the anticipated benefits of marijuana use with potentially significant
      health risks.

PMID- 27891824
TI  - Lipidomic profiling of high-fat diet-induced obesity in mice: Importance of
      cytochrome P450-derived fatty acid epoxides.
AB  - OBJECTIVE: Enzymatic metabolism of polyunsaturated fatty acids leads to formation
      of bioactive lipid metabolites (LMs). Previous studies have shown that obesity
      leads to deregulation of LMs in adipose tissues. However, most previous studies
      have focused on a single or limited number of LMs, and few systematical analyses
      have been carried out. METHODS: A LC-MS/MS-based lipidomics approach was used,
      which can analyze >100 LMs produced by cyclooxygenase, lipoxygenase, and
      cytochrome P450 (CYP) enzymes, to analyze the profile of LMs in high-fat diet
      induced obesity in mice. RESULTS: LC-MS/MS showed that high-fat feeding
      significantly modulated profiles of LMs in adipose tissues. Among the three major
      polyunsaturated fatty acid metabolizing pathways (cyclooxygenase, lipoxygenase,
      and CYP), CYP-derived fatty acid epoxides were the most dramatically altered LMs.
      Almost all types of fatty acid epoxides were reduced by 70% to 90% in adipose
      tissues of high-fat diet-fed mice. Consistent with the reduced levels of fatty
      acid epoxides, the gene expression of several CYP epoxygenases, including Cyp2j5,
      Cyp2j6, and Cyp2c44, was significantly reduced in adipose tissues of high-fat
      diet-fed mice. CONCLUSIONS: Results show that CYP-derived fatty acid epoxides are
      the most responsive LMs in high-fat diet-induced obesity, suggesting that these
      LMs could play critical roles in obesity.

PMID- 27891826
TI  - CT brain perfusion: A static phantom study of contrast-to-noise ratio and
      radiation dose.
AB  - INTRODUCTION: Computed tomography perfusion (CTP) is increasingly employed in the
      diagnosis and management of ischaemic stroke but radiation dose can be
      significant and optimising contrast-to-noise ratio (CNR) is challenging. This
      study aimed to quantify and optimise the balance between CNR as a surrogate for
      image quality and radiation dose. METHODS: A perspex head phantom with vials of
      dilute contrast agent was scanned using a Siemens Definition Flash 128-slice
      scanner. The CTP protocol exposure parameters were adjusted over 70-120 kVp and
      150-285 mAs. Measurements were obtained for the average dose per slice,
      Hounsfield Units (HU) for iodinated contrast agent, and the image noise for
      background regions of perspex. The CNR was measured as a function of the
      volumetric CT dose index (CTDIvol) and kVp. RESULTS: A change from 120 to 80 kVp,
      achieved the same CNR with 60% reduction in dose. Alternatively, for the same
      dose, the change from 120 to 80 kVp improved CNR by +58%. A change from 80 to 70
      kVp while operating at the same CNR, led to 13% reduction in dose. Alternatively,
      maintaining the same dose while changing from 80 to 70 kVp improved the CNR by
      +7%. CONCLUSION: Lower beam energies achieved the same CNR with less dose, or
      improved CNR at the same dose. A reduction from 80 kVp to 70 kVp may be
      clinically useful to optimise CTP acquisitions.

PMID- 27891825
TI  - Iridium-Catalyzed Stereoselective Allylic Alkylation Reactions with Crotyl
      Chloride.
AB  - The development of the first enantio-, diastereo-, and regioselective iridium
      catalyzed allylic alkylation reaction of prochiral enolates to form an all-carbon
      quaternary stereogenic center with an aliphatic-substituted allylic electrophile
      is disclosed. The reaction proceeds with good to excellent selectivity with a
      range of substituted tetralone-derived nucleophiles furnishing products bearing a
      newly formed vicinal tertiary and all-carbon quaternary stereodyad. The utility
      of this protocol is further demonstrated via a number of synthetically diverse
      product transformations.

PMID- 27891828
TI  - Reducing calories, fat, saturated fat, and sodium in restaurant menu items:
      Effects on consumer acceptance.
AB  - OBJECTIVE: To assess consumer acceptance of reductions of calories, fat,
      saturated fat, and sodium to current restaurant recipes. METHODS: Twenty-four
      menu items, from six restaurant chains, were slightly modified and moderately
      modified by reducing targeted ingredients. Restaurant customers (n = 1,838) were
      recruited for a taste test and were blinded to the recipe version as well as the
      purpose of the study. Overall consumer acceptance was measured using a 9-point
      hedonic (like/dislike) scale, likelihood to purchase scale, Just-About-Right
      (JAR) 5-point scale, penalty analysis, and alienation analysis. RESULTS: Overall,
      modified recipes of 19 menu items were scored similar to (or better than) their
      respective current versions. Eleven menu items were found to be acceptable in the
      slightly modified recipe version, and eight menu items were found to be
      acceptable in the moderately modified recipe version. Acceptable ingredient
      modifications resulted in a reduction of up to 26% in calories and a reduction of
      up to 31% in sodium per serving. CONCLUSIONS: The majority of restaurant menu
      items with small reductions of calories, fat, saturated fat, and sodium were
      acceptable. Given the frequency of eating foods away from home, these reductions
      could be effective in creating dietary improvements for restaurant diners.

PMID- 27891827
TI  - GPX3 methylation in bone marrow predicts adverse prognosis and leukemia
      transformation in myelodysplastic syndrome.
AB  - Epigenetic inactivation of GPX3 has been identified in various cancers including
      leukemia. Moreover, aberrant DNA methylation was also found as a dominant
      mechanism of disease progression in myelodysplastic syndrome (MDS). This study
      intended to explore GPX3 promoter methylation and its clinical relevance in 110
      patients with MDS. GPX3 methylation was examined by real-time quantitative
      methylation-specific PCR (RQ-MSP) and bisulfite sequencing PCR (BSP). GPX3
      methylation was identified in 15% (17/110) MDS patients, and significantly higher
      than controls, and lower than acute myeloid leukemia (AML) patients (P = 0.024
      and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A
      mutation (P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly
      shorter overall survival (OS) time than those with GPX3 unmethylation analyzed
      with Kaplan-Meier analysis (P = 0.012). Moreover, Cox regression analysis
      revealed that GPX3 methylation might act as an independent prognostic indicator
      in MDS (HR = 1.847, P = 0.072). GPX3 methylation density was significantly
      increased during the progression from MDS to secondary acute myeloid leukemia
      (sAML) in three follow-up paired patients. Our study concludes that GPX3
      methylation in bone marrow is associated with adverse prognosis and leukemia
      transformation in MDS.

PMID- 27891829
TI  - Prepregnancy obesity and the racial disparity in infant mortality.
AB  - OBJECTIVE: To estimate the extent to which prepregnancy obesity explains the
      Black-White disparity in stillbirth and infant mortality. METHODS: A population
      based study of linked Pennsylvania birth-infant death certificates (2003-2011; n
      = 1,055,359 births) and fetal death certificates (2006-2011; n = 3,102
      stillbirths) for all singleton pregnancies in non-Hispanic (NH) White and NH
      Black women was conducted. Inverse probability weighted regression was used to
      estimate the role of prepregnancy obesity in explaining the race-infant/fetal
      death association. RESULTS: Compared with NH White women, NH Black women were
      more likely to have obesity (>=30 kg/m2 ) and experienced a higher rate of
      stillbirth (8.3 vs. 3.6 stillbirths per 1,000 live-born and stillborn infants)
      and infant death (8.5 vs. 3.0 infant deaths per 1,000 live births). When the
      contribution of prepregnancy obesity was removed, the difference in risk between
      NH Blacks and NH Whites decreased from 6.2 (95% CI: 5.6-6.7) to 5.5 (95% CI: 4.9
      6.2) excess stillbirths per 1,000 and 5.8 (95% CI: 5.3-6.3) to 5.2 (95% CI: 4.7
      5.7) excess infant deaths per 1,000. CONCLUSIONS: For every 10,000 live births in
      Pennsylvania (2003-2011), 6 of the 61 excess infant deaths in NH Black women and
      5 of the 44 excess stillbirths (2006-2011) were attributable to prepregnancy
      obesity.

PMID- 27891830
TI  - A randomized trial Examining The Impact Of Communicating Genetic And Lifestyle
      Risks For Obesity.
AB  - OBJECTIVE: Genetic testing for obesity is available directly to consumers, yet
      little is understood about its behavioral impact and its added value to
      nongenetic risk communication efforts based on lifestyle factors. METHODS: A
      randomized trial examined the short-term impact of providing personalized obesity
      risk information, using a 2 * 2 factorial design. Participants were recruited
      from the Coriell Personalized Medicine Collaborative (CPMC) and randomized to
      receive (1) no risk information (control), (2) genetic risk, (3) lifestyle risk,
      or (4) combined genetic/lifestyle risks. Baseline and 3-month follow-up survey
      data were collected. Analyses examined the impact of risk feedback on intentions
      to lose weight and self-reported weight. RESULTS: A total of 696 participants
      completed the study. A significant interaction effect was observed for genetic
      and lifestyle information on intent to lose weight (P = 0.0150). Those who
      received genetic risk alone had greater intentions at follow-up, compared with
      controls (P = 0.0034). The impact of receiving elevated risk information on
      intentions varied by source and combination of risks presented. Non-elevated
      genetic risk did not lower intentions. No group differences were observed for
      self-reported weight. CONCLUSIONS: Genetic risk information for obesity may add
      value to lifestyle risk information depending on the context in which it is
      presented.

PMID- 27891831
TI  - Race, obesity, and birth outcomes: Unraveling a complex association to improve
      maternal-child health.

PMID- 27891832
TI  - Cortisol in human milk predicts child BMI.
AB  - OBJECTIVE: Breastfeeding has been linked to lower rates of childhood obesity.
      Human milk contains cortisol, known to regulate glucose storage and metabolism.
      The aim of this study was to to test the hypothesis that early exposure to
      cortisol in human breast milk helps to modulate infant body mass index (BMI)
      trajectories over the first 2 years of life. METHODS: Growth curve modeling was
      used to examine whether infant exposure to cortisol in human milk at 3 months
      predicted changes in child body mass index percentile (BMIP) at 6, 12, and 24
      months of age in 51 breastfeeding mother-child pairs. RESULTS: Infants exposed to
      higher milk cortisol levels at 3 months were less likely to exhibit BMIP gains
      over the first 2 years of life, compared with infants exposed to lower milk
      cortisol. By age 2, infants exposed to higher milk cortisol levels had lower
      BMIPs than infants exposed to lower milk cortisol. Milk cortisol was a stronger
      predictor of BMIP change in girls than boys. CONCLUSIONS: Cortisol exposure
      through human milk may help to program metabolic functioning and childhood
      obesity risk. Further, because infant formula contains only trace amounts of
      glucocorticoids, these findings suggest that cortisol in milk is a novel
      biological pathway through which breastfeeding may protect against later obesity.

PMID- 27891837
TI  - Corrigendum.

PMID- 27892208
TI  - Campaign for fair pay is a fight for the NHS.
AB  - NHS finances are in a dire state. Some would say now is not the time to argue for
      a pay increase, but the RCN's reasons for asking the Pay Review Body to recommend
      a 2017 pay award above the 1% cap are compelling.

PMID- 27892209
TI  - How to develop your emotional resilience.
AB  - Although physical or emotional abuse at work is never acceptable, many people can
      be less aware of social niceties when they are unwell or stressed, so, sometimes
      you may be on the receiving end of harsh comments from patients.

PMID- 27892210
TI  - Domestic abuse: what you need to know.
AB  - Despite increased recognition of domestic abuse in recent years, it often remains
      hidden. While some healthcare professionals are aware of abuse and have a good
      understanding of the difficulties in addressing the needs of those affected, this
      is not always the case.

PMID- 27891833
TI  - Metabolomics-guided insights on bariatric surgery versus behavioral interventions
      for weight loss.
AB  - OBJECTIVE: To review the metabolomic studies carried out so far to identify
      metabolic markers associated with surgical and dietary treatments for weight loss
      in subjects with obesity. METHODS: The Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Thirty-two
      studies successfully met the eligibility criteria. The metabolic adaptations
      shared by surgical and dietary interventions mirrored a state of starvation
      ketoacidosis (increase of circulating ketone bodies), an increase of
      acylcarnitines and fatty acid beta-oxidation, a decrease of specific amino acids
      including branched-chain amino acids (BCAA) and (lyso)glycerophospholipids
      previously associated with obesity, and adipose tissue expansion. The metabolic
      footprint of bariatric procedures was specifically characterized by an increase
      of bile acid circulating pools and a decrease of ceramide levels, a greater
      perioperative decline in BCAA, and the rise of circulating serine and glycine,
      mirroring glycemic control and inflammation improvement. In one study, 3
      hydroxybutyrate was particularly identified as an early metabolic marker of long
      term prognosis after surgery and proposed to increase current prognostic
      modalities and contribute to personalized treatment. CONCLUSIONS: Metabolomics
      helped in deciphering the metabolic response to weight loss treatments. Moving
      from association to causation is the next challenge to move to a further level of
      clinical application.

PMID- 27892211
TI  - Student life - How to relay complex information to patients.
AB  - Nurses play a vital role in helping patients understand what is happening to
      them, so it is important that you get into the habit of using clear communication
      and checking for understanding.

PMID- 27892212
TI  - Loneliness could be a predictor for Alzheimer's disease.
AB  - Lonely people have an increased risk of developing Alzheimer's disease because
      they have high levels of the protein amyloid in the brain, suggest US
      researchers.

PMID- 27892213
TI  - Monitoring of medicines helps prevent adverse side effects.
AB  - Nurse-led monitoring of medicines taken by people with mental health conditions
      can prevent serious adverse side effects, reveals new research.

PMID- 27892214
TI  - Education's 'leap into the dark' an unknown in effort to cut attrition.
AB  - Drop-out rates among nursing students have been a concern for years. Nursing
      Standard was first to reveal the scale of the problem a decade ago, when a
      quarter of those who started their courses were not making it to the end. The
      situation has barely improved since.

PMID- 27892216
TI  - RCN Wales nurse of the year showed exceptional leadership in child health.
AB  - A children's consultant nurse has been named RCN Wales nurse of the year for her
      leadership and work to help a child with complex needs to attend a mainstream
      school.

PMID- 27892217
TI  - Significant adult weight gain can increase risk of cancer.
AB  - Substantial weight gain over many years significantly increases the risk of
      obesity-related cancers, say researchers from the University of Manchester and
      The Health eResearch Centre.

PMID- 27892219
TI  - Supply and training issues hit district nurse numbers.
AB  - District nurse numbers are declining in more than half the trusts that employ
      them.

PMID- 27892220
TI  - Government sets 'ambitious' target to cut student attrition.
AB  - High numbers of students dropping out of nursing courses have been a concern in
      the profession for decades. But efforts to reverse the trend are now underway,
      with the government instructing Health Education England (HEE) to reduce
      'avoidable' drop-out rates by 50% by 2017.

PMID- 27892221
TI  - Nurse shortage in care homes 'critical'.
AB  - The care home sector in Scotland is facing an 'intolerable' shortage of nurses,
      with one in four nursing posts vacant, according to a new report.

PMID- 27892222
TI  - Diluting hospital nursing skill mix 'not in the public interest'.
AB  - Implementing policies to dilute hospital nursing skill mix should be treated with
      caution because it can have life-threatening consequences for patients, say
      researchers.

PMID- 27892223
TI  - HEE redefines nursing associate responsibilities.
AB  - Nursing associates will only be able to administer medicines if suitably trained
      and competent, in settings where it is deemed appropriate, and will be guided by
      employer medicines management policies, according to Health Education England
      (HEE).

PMID- 27892224
TI  - Good hand hygiene is essential.
AB  - During a second-year placement on a 25-bed medical ward, I attended a ward round
      with a medical consultant and his team, to observe how they assessed patients and
      decided on a care plan. The team was made up of seven staff members, including
      four junior doctors. They saw about 13 patients on our ward before heading to
      other wards.

PMID- 27892229
TI  - Unison Scotland Duty of Care.
AB  - Unison Scotland has launched an app that allows nurses and midwifes to register
      concerns about care in Scotland's hospitals.

PMID- 27892230
TI  - Clinical academic careers: embracing the art and science of nursing.
AB  - Clinical academics make a unique contribution to health research and scholarship
      by undertaking practice-focused research that offers direct benefits to patient
      care. The Florence Nightingale Foundation supports the development of research
      skills in nursing and midwifery through its scholarships and by establishing a
      network of chairs in clinical nursing practice research. The Florence Nightingale
      Foundation also provides leadership scholarships to deans and aspiring deans of
      university faculties of health. It is from these perspectives that the case is
      made for investment in clinical academic roles and the development of career
      pathways that embrace the art and science of nursing.

PMID- 27892226
TI  - An overview of the management of patients with chronic pancreatitis.
AB  - Chronic pancreatitis is a complex inflammatory condition characterised by
      irreversible damage to the pancreas. This article explores the pathophysiology of
      this condition and its effects on pancreatic function. It outlines the causes and
      presenting features of chronic pancreatitis, as well as its effect on patients'
      quality of life and the changes to their lifestyle that are likely to be
      required. Chronic pancreatitis cannot be cured; therefore, treatment aims to
      control pain, manage problems associated with malabsorption, and assess and
      manage long-term complications that may develop, such as insulin dependence.

PMID- 27892231
TI  - Politicians should try working a 12 hour shift.
AB  - In response to the online story, RCN calls government response to pay petition
      'completely inadequate', I challenge any politician to work for 12 hours, which
      is the length of most front-line shifts.

PMID- 27892232
TI  - Teething.
AB  - Essential facts Teething is a normal physiological process when a baby's first
      set of teeth emerge through the gums. Most babies grow their first tooth at some
      point during their first year. Babies can experience teething differently, with
      some showing signs of distress.

PMID- 27892233
TI  - A new job in a new country.
AB  - Nurses hoping to uproot and work overseas will find attractive packages in
      Australia and the Middle East, with particular opportunities for short-term
      relocation to Dubai.

PMID- 27892234
TI  - Substituting nurses puts lives at risk, study finds.
AB  - Replacing professionally qualified nurses with lower-skilled nursing assistants
      is linked to a heightened risk of patient death, a new study has shown.

PMID- 27892235
TI  - Shout louder about poor pay.
AB  - It seems increasingly clear to me that the NHS pay campaign is not making waves
      either in the NHS or with the public.

PMID- 27892236
TI  - 1 in 100 babies: the fetal alcohol spectrum disorder pathway.
AB  - Alcohol consumed during pregnancy is the nation's leading preventable cause of
      developmental disabilities and birth defects. One in 100 babies is estimated to
      be born with alcohol-related damage, according to the World Health Organization.
      Fetal alcohol spectrum disorders (FASDs) are more common than autism but are
      under-diagnosed.

PMID- 27892237
TI  - 'Every family going through trauma in PICU deserves a nurse like Fiona'.
AB  - It is hard to sum up in a few words what makes nurse consultant Fiona Lynch so
      utterly exceptional.

PMID- 27892240
TI  - Domestic violence advisers should be introduced at every hospital, says charity.
AB  - Introducing specialist domestic abuse advisers in hospitals would help nurses
      provide better support to victims, a charity says.

PMID- 27892241
TI  - Can I tell you a secret?'
AB  - As a general nursing student the question I dreaded hearing was 'am I dying
      nurse?'. Thankfully I can't recall being asked it, but like many of my peers I
      worried about such situations, for which I felt poorly prepared.

PMID- 27892242
TI  - Women who have 'non-lump' breast cancer symptoms delay seeking medical advice.
AB  - About one in six women diagnosed with breast cancer go to their doctor with a
      symptom other than a lump, say researchers from University College London who
      studied the data of more than 2,300 women diagnosed with breast cancer in England
      in 2009-10.

PMID- 27892244
TI  - Parents who lack social confidence have shy babies.
AB  - Babies whose parents feel uncomfortable in social situations are less interested
      in other people, a study suggests.

PMID- 27892245
TI  - A minister's average pay is nearly three times that of a nurse.
AB  - The government argues that nurses' pay is already above the national average and
      that many of us receive pay progression increments.

PMID- 27892246
TI  - Support nurses in adversity.
AB  - A few weeks ago an intrepid band of RCN members walked the 96 miles of the West
      Highland Way to raise funds for the RCN Foundation.

PMID- 27892247
TI  - Family satisfaction with patient care in critical care units in Pakistan: a
      descriptive cross-sectional study.
AB  - AIM: To assess family satisfaction with care provided to patients in critical
      care units in Islamabad. METHOD: A descriptive cross-sectional study was
      conducted in 11 medical and surgical critical care units at two private hospitals
      in Islamabad, Pakistan. The purposive sample consisted of 323 immediate family
      members and other relatives and friends (referred to as family members in this
      article) of 323 patients admitted to the critical care units for at least 24
      hours. The revised Critical Care Family Satisfaction Survey was used for data
      collection. Descriptive statistics were used for data analysis. FINDINGS: A total
      of 149/323 (46%) family members were 'very satisfied' with the honesty (openness)
      of staff in explaining the patient's condition, and 137/323 (42%) family members
      were 'very satisfied' with the nurses' availability to speak to them. A total of
      143/323 (44%) family members were 'satisfied' with the honesty (openness) of
      staff in explaining the patient's condition, and 131/323 (41%) were 'satisfied'
      with the nurses' availability to speak to them. A few family members (21/323, 6%)
      were 'very dissatisfied' with the flexibility of the visiting hours and a few
      (20/323, 6%) were 'very dissatisfied' with the noise level in the critical care
      units. Some family members (38/323, 12%) were 'not satisfied' with the
      flexibility of the visiting hours, and some (18/323, 6%) were 'not satisfied'
      with the noise level in the critical care units. CONCLUSION: The majority of
      family members (244/323, 75%) were 'satisfied' or 'very satisfied' that their
      relatives' needs were being met in the critical care units. However, qualitative
      data indicate that most family members wanted greater involvement in decision
      making. These findings should be considered by staff working in critical care
      settings to ensure high-quality patient care.

PMID- 27892248
TI  - Human immunodeficiency virus.
AB  - What was the nature of the CPD activity, practice-related feedback and/or event
      and/or experience in your practice? The CPD article discussed the importance of
      human immunodeficiency virus (HIV) testing and diagnosing the condition as early
      as possible, so that antiretroviral treatment can be initiated and patient
      outcomes improved.

PMID- 27892249
TI  - Should I lend a student one of my projects?
AB  - Helping a student is to be applauded and there is nothing legally or ethically
      wrong with what you propose, but there is an issue with potential plagiarism,
      whether intentional or not.

PMID- 27892250
TI  - Offshore nurse.
AB  - A former deep sea fisherman is setting sail for a new nursing role ensuring
      offshore oil and gas workers stay safe.

PMID- 27892251
TI  - Readers' panel - Is the 1% pay cap for NHS staff destroying nurses' morale?
AB  - Our experts consider a hot topic of the day.

PMID- 27892252
TI  - 'Be bolder and more tenacious'.
AB  - Diana Greenfield graduated in 1988 from Bristol Polytechnic. She began work in
      oncology in 2001 at Sheffield Teaching Hospitals NHS Foundation Trust, where she
      set up the collaborative late effects of cancer treatment research group. In 2009
      she took on her present role as nurse consultant and clinical lead for the late
      effects clinical service. She lives in Sheffield and has two sons, aged 18 and
      21.

PMID- 27892253
TI  - It's good to talk.
AB  - Can we get a move on, sister?' the patient asked anxiously. She had come for a
      preoperative assessment, a lengthy process involving several stages. 'I have to
      catch the bus back to Little Widdling-on-the-Marsh at three o'clock and there's
      only one a week. If I miss it, I'm done for.'

PMID- 27892254
TI  - Resilience is key to good leadership.
AB  - As the dust settles in the US, and the world comes to terms with Donald Trump
      being the US president-elect, my thoughts are with Hillary Clinton.

PMID- 27892396
TI  - A topography of free kicks in soccer.
AB  - This study investigates the spatial relationship of performance variables for
      soccer free kicks. In order to suggest ways in which players might optimise their
      performance, we collected data from free kicks (<35 m to goal line) of two German
      Bundesliga seasons (2013/14, 2014/15) (n = 1624). In the analysis, we applied the
      ISO-map approach using colour gradients to visualise the mean values of a
      variable on a 2D-map of the pitch. Additionally, variograms were used to describe
      the degree of spatial dependence of the free kick variables. Results show that
      DENSITY, TYPE OF PLAY, PLAYERS IN WALL, DISTANCE TO WALL and RULE VIOLATION were
      strongly spatially dependent. Centrality and proximity to the goal increased the
      variables PLAYERS IN WALL, RULE VIOLATIONS and INTERRUPTION TIME, and the ratio
      of goals scored increased from 5.9% (central far) to 10.9% (central near). In
      70.9% of the shots, players preferred a switched laterality, which did not result
      in a higher success rate. Furthermore, there was no statistical advantage for the
      defensive team when DISTANCE TO WALL was below 9.15 m or when there was a RULE
      VIOLATION. Crosses had a success rate (i.e., first controlled ball contact after
      the cross) of 20.8%. Played with natural laterality, they were 5% more successful
      than with switched laterality. Crosses from the right side outside the penalty
      box were 10% more successful than from the left side. Therefore, it might be
      worthwhile practising the defence of balls coming from this side.

PMID- 27892397
TI  - Science and medicine in football: progress & evolution.

PMID- 27892398
TI  - Therapy-resistant septic olecranon bursitis due to Mycobacterium gordonae.
AB  - INTRODUCTION: Septic olecranon bursitis due to atypical mycobacteria is rare. An
      insidious beginning can delay diagnosis and treatment. Antibacterial therapy
      recommendations are not well-defined for bursitis caused by atypical
      mycobacteria. We present a rare case of olecranon bursitis caused by
      Mycobacterium gordonae, reporting our experiences regarding pathogen
      identification and antibiotic therapy, which differs from regimes used in common
      septic bursitis mostly caused by staphylococcus aureus. METHODS: A 35-year-old
      male with bursitis olecrani received open bursectomy. Microbiological culture did
      not reveal bacteria. Due to wound healing complications revision surgery was
      performed four weeks postoperatively. Finally, Mycobacterium gordonae was
      identified by PCR and an antibiogram could be developed. A triple antimicrobial
      combination therapy with Rifampicin, Clarithromycin, and Ethambutol was
      administered systemically for 12 months. The patient was followed-up for 24
      months. RESULTS: After the second operation with pathogen identification and
      antibiotic combination therapy the wound healed without any additional
      complications. At last follow-up 24 months after the first surgery with
      bursectomy and 23 months after revision surgery with debridement, the patient was
      still pain free with no significant clinical findings or tenderness to touch at
      the operation site. Elbow range of motion was full. DISCUSSION: As septic
      bursitis can be caused by many different and sometimes rare and difficult to
      identify bacteria, intraoperative probes should be taken and histopathological
      and microbiological analysis should be conducted, including PCR. In a young man
      with olecranon bursitis due to Mycobacterium gordonae surgical treatment and an
      antibiotic combination therapy showed a good clinical outcome after one and two
      years.

PMID- 27892399
TI  - A suture technique for easier reduction and repair of bucket-handle meniscal
      tears while using the all-inside devices.
AB  - Arthroscopic repair of bucket-handle meniscal tears is difficult due to their
      complex pathology. Many meniscal repair techniques such as all-inside, inside
      out, and outside-in have been described for the treatment of these tears. Loss of
      reduction is a likely complication with the use of new-generation, all-inside
      suture instruments, as the tip of the needle is extracted following advancement
      of the first implant behind the capsule. The complication may be encountered
      quite often and renders the use of the meniscus repair instrument unusable and
      causes an irreparable iatrogenic injury in the meniscus. The application of a
      simpler and more efficient technique is necessary until surgical experience is
      gained. The aim of this study was to define a new, simpler, and more efficient
      combination of suturing method in the treatment of bucket-handle meniscal repairs
      and minimize the rate of complications which may be caused by this technique.

PMID- 27892400
TI  - Increase in CD4+ T-Cell Count at the Time of HIV Diagnosis and Antiretroviral
      Treatment Initiation Among Persons With HIV in New York City.
AB  - BACKGROUND:  Trends in CD4+ T-cell count at human immunodeficiency virus (HIV)
      infection diagnosis and antiretroviral therapy (ART) initiation can be
      characterized using laboratory tests from surveillance. METHODS:  We used CD4+ T
      cell counts and viral loads from New York City for persons who received a
      diagnosis of HIV infection during 2006-2012. RESULTS:  From 2006 to 2012, the
      median CD4+ T-cell count increased from 325 to 379 cells/uL at diagnosis and from
      178 to 360 cells/MUL at ART initiation. CD4+ T-cell counts were consistently
      lower in women, blacks, Hispanics, persons who inject drugs, and heterosexuals.
      DISCUSSION:  Increases in CD4+ T-cell count at diagnosis and ART initiation
      suggest that the time from HIV infection to ART initiation has been reduced
      substantially in New York City.

PMID- 27892401
TI  - Xu et al (J Infect Dis 2013; 208:528-38).

PMID- 27892407
TI  - Metabolomics, nutrition and why epidemiology matters.

PMID- 27892408
TI  - Over-density of population in cities [A letter to the Scientific American, 1879].

PMID- 27892409
TI  - Data Resource Profile: Danish online drug use statistics (MEDSTAT).

PMID- 27892410
TI  - Short-term NO2 exposure is associated with long-chain fatty acids in prospective
      cohorts from Augsburg, Germany: results from an analysis of 138 metabolites and
      three exposures.
AB  - BACKGROUND: Short-term exposure to air pollution is associated with morbidity and
      mortality. Metabolites are intermediaries in biochemical processes, and
      associations between air pollution and metabolites can yield unique mechanistic
      insights. METHODS: We used independent cross-sectional samples with targeted
      metabolomics (138 metabolites across five metabolite classes) from three cohort
      studies, each a part of the Cooperative Health Research in the Region of Augsburg
      (KORA). The KORA cohorts are numbered (1 to 4) according to which survey they
      belong to, and lettered S or F according to whether the survey was a baseline or
      follow-up survey. KORA F4 (N = 3044) served as our discovery cohort, with KORA S4
      (N = 485) serving as the primary replication cohort. KORA F4 and KORA S4 were
      primarily fasting cohorts. We used the non-fasting KORA F3 (N = 377) cohort to
      evaluate replicated associations in non-fasting individuals, and we performed a
      random effects meta-analysis of all three cohorts. Associations between the 0-4
      day lags and the 5-day average of particulate matter (PM)2.5, NO2 and ozone were
      modelled via generalized additive models. All air pollution exposures were scaled
      to the interquartile range, and effect estimates presented as percent changes
      relative to the geometric mean of the metabolite concentration (DeltaGM).
      RESULTS: There were 10 discovery cohort associations, of which seven were
      lysophosphatidylcholines (LPCs); NO2 was the most ubiquitous exposure (5/10). The
      5-day average NO2-LPC(28:0) association was associated at a Bonferroni corrected
      P-value threshold (P < 1.2x10-4) in KORA F4 [DeltaGM = 11.5%; 95% confidence
      interval (CI) = 6.60, 16.3], and replicated (P < 0.05) in KORA S4 (DeltaGM =
      21.0%; CI = 4.56, 37.5). This association was not observed in the non-fasting
      KORA F3 cohort (DeltaGM = -5.96%; CI = -26.3, 14.3), but remained in the random
      effects meta-analysis (DeltaGM = 10.6%; CI = 0.16, 21). CONCLUSIONS: LPCs are
      associated with short-term exposure to air pollutants, in particular NO2 Further
      research is needed to understand the effect of nutritional/fasting status on
      these associations and the causal mechanisms linking air pollution exposure and
      metabolite profiles.

PMID- 27892412
TI  - Commentary: Mendelian randomization analysis identifies circulating vitamin D as
      a causal risk factor for ovarian cancer.

PMID- 27892413
TI  - Association between low resting heart rate and violent behaviour.

PMID- 27892411
TI  - Metabolic signatures of birthweight in 18 288 adolescents and adults.
AB  - BACKGROUND: Lower birthweight is associated with increased susceptibility to
      cardiometabolic diseases in adulthood, but the underlying molecular pathways are
      incompletely understood. We examined associations of birthweight with a
      comprehensive metabolic profile measured in adolescents and adults. METHODS: High
      throughput nuclear magnetic resonance metabolomics and biochemical assays were
      used to quantify 87 circulating metabolic measures in seven cohorts from Finland
      and the UK, comprising altogether 18 288 individuals (mean age 26 years, range 15
      75). Metabolic associations with birthweight were assessed by linear regression
      models adjusted for sex, gestational age and age at blood sampling. The metabolic
      associations with birthweight were compared with the corresponding associations
      with adult body mass index (BMI). RESULTS: Lower birthweight adjusted for
      gestational age was adversely associated with cardiometabolic biomarkers,
      including lipoprotein subclasses, fatty acids, amino acids and markers of
      inflammation and impaired liver function (P < 0.0015 for 46 measures).
      Associations were consistent across cohorts with different ages at metabolic
      profiling, but the magnitudes were weak. The pattern of metabolic deviations
      associated with lower birthweight resembled the metabolic signature of higher
      adult BMI (R2 = 0.77) assessed at the same time as the metabolic profiling. The
      resemblance indicated that 1 kg lower birthweight is associated with similar
      metabolic aberrations as caused by 0.92 units higher BMI in adulthood.
      CONCLUSIONS: Lower birthweight adjusted for gestational age is associated with
      adverse biomarker aberrations across multiple metabolic pathways. Coherent
      metabolic signatures between lower birthweight and higher adult adiposity suggest
      that shared molecular pathways may potentially underpin the metabolic deviations.
      However, the magnitudes of metabolic associations with birthweight are modest in
      comparison to the effects of adiposity, implying that birthweight is only a weak
      indicator of the metabolic risk profile in adulthood.

PMID- 27892414
TI  - Heart rate reactivity and antisocial behaviour.

PMID- 27892415
TI  - Re: Asbestos and product defence science.

PMID- 27892416
TI  - Asbestos and product defence science. Response to: Boffetta and La Vecchia.

PMID- 27892419
TI  - eHealth: From unfulfilled promises to large-scale application.

PMID- 27892420
TI  - eHealth in cardiovascular medicine: A clinical update.
AB  - Demographic changes, progress in medicine technology and regional problems in
      providing healthcare to low density populations are posing great challenges to
      our healthcare systems. Rapid progress in computer sciences and information
      technologies have a great impact on the way healthcare will be delivered in the
      near future. This article describes opportunities and challenges of eHealth and
      telemedicine in the framework of our health systems and, in particular, in the
      context of today's cardiology services. The most promising applications of
      eHealth and telemedicine include: (a) prevention and lifestyle interventions; (b)
      chronic disease management including hypertension, diabetes and heart failure;
      (c) arrhythmia detection including early detection of atrial fibrillation and
      telemonitoring of devices such as pacemaker, internal cardioverter defibrillators
      and implantable rhythm monitoring devices; (d) telerehabilitation. Major
      obstacles to the integration of eHealth and telemedicine into daily clinical
      practice include limited large-scale evidence, in particular, for cost
      effectiveness, as well as lack of interoperability, inadequate or fragmented
      legal frameworks and lack of reimbursement. An important challenge for those
      involved in these new technologies will be to keep the main focus on patient's
      individual needs and to carefully evaluate the evidence behind the practice.

PMID- 27892421
TI  - Screening for atrial fibrillation during influenza vaccinations by primary care
      nurses using a smartphone electrocardiograph (iECG): A feasibility study.
AB  - BACKGROUND: People with unknown atrial fibrillation (AF), who are often
      asymptomatic, have a substantially increased risk of stroke. Although recommended
      in European guidelines, AF screening is not routinely performed. Screening at the
      time of influenza vaccination presents an ideal opportunity to detect AF in large
      numbers in a primary care medical setting, with an existing annual recall system
      for patients aged >=65 years. DESIGN: Cross-sectional pilot study of handheld
      smartphone electrocardiogram (iECG) screening to identify unknown AF. METHODS:
      General practices in Sydney, Australia, were recruited during the influenza
      vaccination period of April-June 2015. Practice nurses screened patients aged
      >=65 years with a 30-second iECG, which has a validated algorithm for detecting
      AF in real time. In order to confirm the accuracy of the algorithm, two research
      cardiologists reviewed de-identified iECGs. In order to explore barriers and
      enablers, semi-structured interviews were conducted with selected nurses,
      practice managers and general practitioners. RESULTS: Five general practices were
      recruited, and 973/2476 (39%) patients attending influenza vaccination were
      screened. Screening took an average of 5 minutes (range 1.5-10 minutes); however,
      abnormal iECGs required additional time. Newly identified AF was found in 8/973
      patients (0.8%). The sensitivity of the iECG automated algorithm was 95% (95%
      confidence interval: 83-99%) and the specificity was 99% (95% confidence
      interval: 98-100%). Screening by practice nurses was well accepted by practice
      staff. Key enablers were the confidence and competence of nurses and a
      'designated champion' to lead screening at the practice. Barriers were practice
      specific, and mainly related to staff time and funding. CONCLUSIONS: Screening
      with iECG during influenza vaccination by primary care nurses is feasible and
      well accepted by practice staff. Addressing barriers is likely to increase
      uptake.

PMID- 27892422
TI  - Prognostic value of serial six-minute walk tests using tele-accelerometry in
      patients with chronic heart failure: A pre-specified sub-study of the TIM-HF
      Trial.
AB  - BACKGROUND: The six-minute walk test (6MWT) is an established functional test
      assessing exercise capacity and is used to predict clinical prognosis in patients
      with chronic heart failure (HF). Tele-accelerometry is a novel approach to
      activity monitoring using telemedical data transfer and allows a Tele-6MWT to be
      performed in an outpatient setting. It offers patients the option of performing
      simple serial follow-up tests in their own home. AIMS: The aim of this study was
      to investigate the prognostic value of serial Tele-6MWTs using tele-accelerometry
      in patients with HF. DESIGN/METHODS: In this proof-of-concept study, 155 patients
      with HF completed the Tele-6MWT in an outdoor setting once per month over a
      period of 0.25-21 months. We analysed the differences in the number of steps over
      time to predict hospitalization as a result of HF or death. RESULTS: Patients
      with at least one event (n = 31) recorded a lower number of steps and a shorter
      distance in Tele-6MWT at baseline compared with patients who remained event-free
      (n = 124) (540.1 +/- 78.4 steps vs. 601.8 +/- 76.7 steps, P < 0.001 respectively;
      353.2 +/- 82.4 m vs. 418.8 +/- 95.6 m, P < 0.001). Patients (n = 19) who
      performed more than one Tele-6MWT prior to a clinical event showed no significant
      difference in the number of steps, regardless of whether the baseline test was
      compared with the last Tele-6MWT before the event or with the last two tests
      before the event. CONCLUSION: Tele-6MWT has a high predictive value with respect
      to hospitalization as a result of HF or death from any cause and the results were
      comparable with the prognostic impact of a conventional 6MWT. Therefore Tele-6MWT
      may be used as alternative test method in the home environment. However, there is
      no added prognostic value of repeating Tele-6MWTs on a monthly basis.

PMID- 27892424
TI  - The Invention of Nature: The Adventures of Alexander von Humboldt, the Lost Hero
      of Science (UK). The Invention of Nature: Alexander von Humboldt's New World
      (USA). - By Andrea Wulf.

PMID- 27892423
TI  - A EUropean study on effectiveness and sustainability of current Cardiac
      Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised
      controlled trial.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is an evidence-based intervention to
      increase survival and quality of life. Yet studies consistently show that elderly
      patients are less frequently referred to CR, show less uptake and more often drop
      out of CR programmes. DESIGN: The European study on effectiveness and
      sustainability of current cardiac rehabilitation programmes in the elderly (EU
      CaRE) project consists of an observational study and an open prospective,
      investigator-initiated multicentre randomised controlled trial (RCT) involving
      mobile telemonitoring guided CR (mCR). OBJECTIVE: The aim of EU-CaRE is to map
      the efficiency of current CR of the elderly in Europe, and to investigate whether
      mCR is an effective alternative in terms of efficacy, adherence and
      sustainability. METHODS AND RESULTS: The EU-CaRE study includes patients aged 65
      years or older with ischaemic heart disease or who have undergone heart valve
      surgery. A total of 1760 patients participating in existing CR programmes in
      eight regions of Europe will be included. Of patients declining regular CR, 238
      will be included in the RCT and randomised in two study arms. The experimental
      group (mCR) will receive a personalised home-based programme while the control
      group will receive no advice or coaching throughout the study period. Outcomes
      will be assessed after the end of CR and at 12 months follow-up. The primary
      outcome is VO2peak and secondary outcomes include variables describing CR uptake,
      adherence, efficacy and sustainability. CONCLUSION: The study will provide
      important information to improve CR in the elderly. The EU-CaRE RCT is the first
      European multicentre study of mCR as an alternative for elderly patients not
      attending usual CR.

PMID- 27892425
TI  - Natural Kinds and Classification in Scientific Practice. - Edited by Catherine
      Kendig.

PMID- 27892431
TI  - Childhood Injury Prevention in Post-epidemiological Transition in Nepal.

PMID- 27892432
TI  - Reliability and Validity of the Nepali Wolf Motor Function Test following Cross
      cultural Adaptation.
AB  - Background The Wolf motor function test is a standardized, reliable and valid
      performance-based measure, which evaluates upper-extremity function. Neither
      there is any evidence of neurological measure in Nepali nor has this tool been
      cross-culturally adapted to date. Objective To cross-culturally translate and
      evaluate reliability and validity of Nepali Wolf motor function test. Method Two
      forward-translators translated the original version into Nepali. After
      synthesizing, two back- translators translated it into English. The expert
      committee consolidated and derived a final Nepali version. Two assessors
      pretested on three participants to confirm that the original concept of the tool
      is preserved. The agreement and correlation between back-translators were
      evaluated. The inter- and intra-rater reliability and agreement of two
      physiotherapists on eight participants were demonstrated through intra-class
      correlation- coefficient and weighted-kappa for time and functional ability
      respectively. Criterion validity was explored against Fugl- Meyer assessment
      scale. Result A cross-culturally adapted Nepali Wolf motor function test was
      pretested and ensured that the Nepali version was still retaining its equivalence
      (rho: 0.74 to 1.0 for time, 0.82 to 1.0 for functional ability). Good-to-
      excellent inter- and intra-rater reliability {intra-class-correlation
      coefficient(2,1) and (3,1): 0.80 to 1.0 and 0.81 to 1.0 respectively} were
      demonstrated. Excellent agreement (kappa 0.90, p <0.00) and good correlation (rho
      0.57 to 1.0) between back-translators were found. An adequate criterion validity
      (rho -0.95 for time, 0.91 for functional ability) against Fugl-Meyer assessment
      scale has been demonstrated. Conclusion A cross-culturally adapted Nepali Wolf
      motor function test, preserving its original concept, was developed, and the
      reliability and validity of the tool on individuals with stroke has been
      demonstrated.

PMID- 27892433
TI  - Efficacy of Prophylactic B-Lynch Suture during Lower Segment Caesarian Section in
      High Risk Patients for Atonic Postpartum Haemorrhage.
AB  - Background Postpartum Haemorrhage causes significant maternal mortality and
      morbidity all over the world. Active management of the third stage of labour with
      oxytocics is come into practice. If postpartum haemorrhage is anticipated
      conservative surgical procedures like B-lynch suture is being applied. Objective
      To evaluate the effect of elective B-Lynch suture in preventing atonic postpartum
      haemorrhage during emergency caesarian section with high risk factors for
      atonicity. Method Forty antenatal women undergoing emergency caesarean section
      with risk factors for atony of the uterus were selected in our study. Thirty five
      women were selected before starting Lower segment caesarian section with risk
      factors like general anaesthesia, chorio-amnionitis, preeclampsia, prolonged
      labour, second stage arrest, multiple gestation and use of magnesium sulphate.
      Five women were selected during the caesarean section where uterus remained
      atonic despite of post delivery oxytocics. Before the closure of uterus B-Lynch
      suture was applied. Need for additional intervention or use of blood transfusion
      was evaluated. The results were analysed by using appropriate statistical method.
      Result Seventy five percent of patients were in the age group of 18 to 23 years.
      Ninety percent were nulliparous and ten percent were parous women. Risk factors
      involved were eclampsia in 20/40 (50%), multiple gestation in 6/40 (15%),
      hydramnios in 6/40 (15%) and prolonged second stage of labour in 4/40 (10%)
      patients. Other risk factors were Chorio-amnionitis in 2/40 (5%) patients and use
      of magnesium sulphate in 2/40 (5%) patients causing uterine atony. The average
      haemoglobin level was 9.8 gms/dl. Pre and post operative haemoglobin levels
      differed by 0.4 to 1.8 gms/dl. There were no complications during the procedure
      and at three months follow up. All women resumed normal menstruation within 40
      days after delivery. Conclusion Elective B-Lynch suture is cheap, quick and
      effective in preventing atonic Postpartum Haemorrhage in women undergoing
      emergency lower segment caesarian section who are at high risk for haemorrhage.

PMID- 27892434
TI  - Clinicomorphological Spectrum of Ovarian Cystic Lesions.
AB  - Background Ovarian cysts, which present as neoplastic and non-neoplastic lesions,
      are the most common gynaecological cause of hospital admissions. Early diagnosis
      is difficult due to asymptomatic nature. Clinical, radiological and gross
      examination alone cannot distinguish benign from malignant lesions, hence,
      histopathological examination is important for diagnostic, therapeutic and
      prognostic approach. Objective The objective of the study is to analyze the
      spectrum of ovarian cystic lesions with their clinico-morphorgical features.
      Method This is a prospective study done in between July 2014 and July 2015 in
      Dhulikhel Hospital-Kathmandu University Hospital. Clinical data of patients were
      obtained from hospital records and requisition submitted along with the tissue
      specimens received in the department. Result A total 84 cases of ovarian cystic
      lesions were studied. Among these, 47 (55.9%) were non-neoplastic lesions, 33
      (39.3%) were benign neoplasms, two (2.4%) were borderline and two (2.4%) were
      malignant neoplasms. The most common nonneoplastic lesions were follicular cysts,
      26 (55.3%) followed by simple cysts 14 (29.8%), hemorrhagic cysts five (10.6%)
      and corpus luteal cysts two (4.3%). Among all neoplasms, 19 (51.4%) were mature
      cystic teratoma followed by 10 (27.0%) cases of mucinous cystadenoma and four
      (10.8%) cases of serous cystadenoma. Between two (5.4%) malignant cases, one was
      immature cystic teratoma and the other was mucinous cystadenocarcinoma. Besides
      these, two (5.4%) cases of borderline mucinous cystadenoma were also present.
      Conclusion Ovarian cystic lesions are difficult to categorize on the basis of
      clinical and radiological findings. Histopathological examination plays a
      significant role to differentiate benign lesion from malignant as well as for the
      proper management.

PMID- 27892436
TI  - Study of Depression, Anxiety and Stress among the Medical Students in two Medical
      Colleges of Nepal.
AB  - Background Medical education is intended to prepare graduates for a promoting
      health and caring for the sick. Medical students are confronted with significant
      academic, psychological and existential stressors. There is insufficient
      information regarding psychological morbidity among Nepalese medical students.
      Objective To determine the prevalence of depression, anxiety and stress, among
      the medical students in Nepal, and its association with sociodemographic
      characteristics. Method A cross-sectional questionnaire based study was conducted
      including all students from first to fifth year of student using convenience
      method of sampling from Kathmandu University Medical School (KUSMS), Dhulikhel
      and Manipal College of Medical Sciences (MCOMS), Pokhara, Nepal. Depression,
      Anxiety and stress were assessed using Depression Anxiety and Stress Scale
      (DASS). Additional questions regarding demographic variables were also included
      in the survey. Data analysis was done on Statistical Package for the Social
      Sciences SPSS version 16. Result A total of 538 students participated in the
      study giving a response rate of 89.6%. Aamong them 56.5% were from age group 21
      25 years, 42.2% were below 20 years and only 1.3% were above 25 years of age.
      Among them 52% were female and 48% were male. Our study found that the overall
      prevalence of depression was 29.9%, anxiety was 41.1% and stress was 27% among
      all participated medical students. Depression was significantly associated (OR
      2.23, 95% CI 1.43-3.47, p<0.001) with living condition (living in hostel or
      rented house). Conclusion The higher level of psychiatric morbidity depression
      29.9%, anxiety 41.1% and stress 27% among undergraduate medical students warrants
      needs for strategic plans to alleviate depression anxiety and the stressors right
      from the time they join medical school and has to be continued till they finish
      the course.

PMID- 27892435
TI  - Awareness-Knowledge and Practices of Dental Waste Management among Private
      Practitioners.
AB  - Background Dental wastes are materials that have been utilized in dental clinics,
      which are no longer wanted for use and therefore discarded. Improper disposal of
      these dental wastes can cause harm to the dentist, the people in immediate
      vicinity of the dentist. Objective The present study was conducted to assess the
      knowledge and practices regarding Dental waste management among private
      practitioners. Method The study population included 186 private practitioners in
      three districts of Karnataka (Coorg, Mysore, Hassan), south India. A pre-tested
      self-administered questionnaire was distributed to assess the knowledge and
      practices regarding dental waste management. Descriptive statistics was used to
      summarize the results. The data will be statistically analyzed using chi-square
      test, correlation. Result Out of 186 study subjects, 71(38%) were females and
      115(62%) were males, Chisquare analysis showed highly significant association
      between qualification of the study participants and their knowledge, practice of
      dental waste management. A statistically significant (0.0001) correlation was
      found between the knowledge and practice scores. Conclusion There was a lacunae
      of knowledge regarding proper biomedical waste disposal among the participants.
      In order to fill this vacuum CDE (Continuing Dental Education) programs have to
      be conducted in pursuance to maintain health of the community.

PMID- 27892437
TI  - Blood Requisition and Utilization Practice in Surgical Patients in a Teaching
      Hospital, Western Nepal.
AB  - Background In surgical patients transfusion of blood is often a life-saving
      measure. Preoperative over-ordering of blood is very common and leads to holding
      up of the blood bank reserve and wastage of resources. Objective The main
      objective of this study was to evaluate the practice of cross-match and
      utilization of blood for general surgeries in a teaching hospital of Nepal, to
      identify the surgical procedures where type and screen can be introduced and to
      formulate a maximum surgical blood-order schedule for those procedures where a
      complete cross-match appears mandatory. Method Three hundred and eighty-eight
      patients of different general surgical procedures over a period of one year were
      evaluated. Blood units cross matched and units transfused intra-operative and
      post-operatively were recorded. Blood utilization was evaluated using the
      following indices: cross-matched to transfused ratio, transfusion probability and
      transfusion index. The maximum surgical blood-order schedule was calculated using
      Mead's criterion. Result Of the 601 blood units arranged for 388 patients, only
      108 units were transfused in 81 patients. The cumulative non-utilisation of cross
      matched blood was 82%. Based on these data, the maximum surgical blood-order
      schedule was calculated for seven common surgical procedures where cross-matching
      was justified. Conclusion Unwarranted cross-matching of blood is done in most
      procedures, especially cholecystectomies, hernia operations, breast surgeries,
      skin grafting, thyroidectomies etc. where a group and screen is adequate.
      Implementation of the recommended maximum surgical blood-order schedule and
      introduction of type and screen for eligible surgical procedures is a safe,
      effective and economic solution.

PMID- 27892438
TI  - Comparison of Initial Response of Nebulized Salbutamol and Adrenaline in Infants
      and young Children Admitted with Acute Bronchiolitis.
AB  - Background Acute bronchiolitis is common cause of hospitalization in infants and
      young children. There are widespread variations in the diagnosis and management.
      Despite the use of bronchodilators for decades, there is lack of consensus for
      the benefit of one above another. Objective To compare initial response of
      nebulized adrenaline and salbutamol. Method Children aged two months to two years
      admitted with acute bronchiolitis in the department of Paediatrics of Manipal
      teaching hospital, Pokhara, Nepal, from 1st March 2014 to 28th February 2015 were
      enrolled. Patients fulfilling inclusion criteria received either adrenaline or
      salbutamol nebulization. Data were collected in a predesigned proforma.
      Respiratory distress assessment instrument (RDAI) scores were considered primary
      outcome measure and respiratory rate at 48 hours, duration of hospital stay,
      requirement of supplemental oxygen and intravenous fluid were considered
      secondary outcome measure. Result A total of 40 patients were enrolled in each
      study group. Mean RDAI scores at admission was in 9.75 with (CI- 9.01, 10.49) in
      adrenaline and 9.77 (CI- 9.05, 10.50) in salbutamol group. There was gradual
      decline in mean RDAI scores in both the groups over 48 hours to 4.15 (CI-
      3.57,4.73) and 4.13 (CI- 3.69,4.56) in adrenaline and salbutamol group
      respectively. Hospital stay was 5.32 days in adrenaline and 5.68 days in
      salbutamol group. Patients nebulized with adrenaline required oxygen for 33.30
      hours compared with 36.45 hours in salbutamol. Intravenous fluid duration was
      also less in adrenaline group compared to salbutamol group (33.15 vs 37.80
      hours). Conclusion Patients of acute bronchiolitis nebulized with either
      salbutamol or adrenaline experienced similar decline in RDAI scores in the first
      48 hours. Duration of supplementary oxygen and intravenous fluid was less in
      adrenaline group compared with salbutamol group.

PMID- 27892439
TI  - Lichen Planus Pigmentosus: A study for association of Thyroid Dysfunction.
AB  - Background Lichen planus pigmentosus (LPP) is considered a chronic and
      progressive variant of lichen planus. Although pigmentation occurs in the sun
      exposed areas, the etiology remains unknown and there are no appropriate
      treatment guidelines. Association with thyroid disorder has been described in
      various disorders of pigmentation. Objective The objective of this study was to
      find the association between LPP and thyroid dysfunction. Method A total of 54
      clinically diagnosed cases of LPP and 54 age and sex matched healthy control
      volunteers were included in this case control study. Thyroid function test and
      thyroid peroxidase antibody were analysed to determine the probable association
      between thyroid diseases and LPP. Result Seventeen (31.7%) patients had
      biochemical evidence of hypothyroidism and 3 had hyperthyroidism among the
      diseased group. Among the control group two persons were tested positive for
      hypothyroidism (c2 = 0.34; p <0.05). Similarly, the levels of thyroid peroxidase
      antibody in the LPP patients were found to be significantly higher than those of
      controls (p <0.05). Conclusion Thyroid disorder was found to be an associated
      factor in LPP. Hence, we recommend routine thyroid function tests in patients
      with LPP. Further research is warranted among large number of patients to
      elucidate the exact association.

PMID- 27892440
TI  - Urinary Tract Infection in Asymptomatic Newborns with Prolonged Unconjugated
      Hyperbilirubunemia: A Hospital based Observational study from Western Region of
      Nepal.
AB  - Background Urine culture is usually not a part of work-up for neonatal
      unconjugated hyperbilirubinemia; hence its prevalence remains unknown. Objective
      This study was done to determine the incidence of urinary tract infection (UTI)
      in asymptomatic newborns with prolonged unconjugated hyperbilirubinemia and to
      evaluate which other laboratory parameters are associated with UTIs. Method A
      prospective observational study where jaundiced newborns otherwise clinically
      well, were evaluated for UTI. The study was carried out in neonatal intensive
      care unit of Manipal Teaching Hospital, Pokhara from June 2012 -April 2013. The
      babies were divided in two groups group I- late prolonged jaundice and Group II -
      early physiological jaundice. Serum bilirubin, Septic screening and suprapubic
      urine sample analysis was performed for all subjects. Data was analyzed using
      SPSS version 16 and p 7lt; 0.05 was considered statistically significant. Result
      Of the 85 neonates, 33(38.8%) were females and 52(61.2%) males; 68(80%) were of
      term gestation and 17(20%) were preterms. The age at onset of jaundice for group
      I (n=53) was 13.6+/-4.88 days and for Group II (n= 32) was 5.0+/- 1.04 days. 11
      /85 (12.9%) were diagnosed to have UTI [10 (90.9%) in group I and 1 in group II
      (9.01%] (p=0.04). UTI was more prevalent in group I [OR 7.20, 95% CI (0.87,
      59.27)], more prevalent in male [OR 8.40, 95% CI (0.59, 74.13) and term babies of
      group I [OR 4.39, 95% CI (0.48, 39.82) when compared to Group II. Among other lab
      parameters only total WBC count was statistically significant (p=0.03).
      Escherichia coli was the predominant pathogen (45.45%) isolated. The sensitive
      antibiotics were aminoglycosides, fluroquinolones, nitrofurantoin and vancomycin
      and resistant antibiotics were most cephalosporins and penicillins for the
      isolated organisms. Conclusion The present study highlights significant
      association between late prolonged unconjugated hyperbilirubinemia and UTI. It is
      suggested that evaluation for UTI may be considered as a screening test for such
      cases.

PMID- 27892441
TI  - A Prospective Study of Commonly Prescribed Drugs in the Management of Neuropathic
      Pain and its Medication Adherence Pattern.
AB  - Background Neuropathic pain is one of the common complains of patients visiting
      neurology and orthopedic departments in hospitals. Management of neuropathic pain
      is difficult and is often symptomatic rather than being curative. Adherence to
      medication is necessary for pain management to be effective. However, there are
      various factors related to patient, physician, drug regimen and other socio
      economic affecting adherence. Objective To study commonly prescribed drugs in
      neuropathic pain management and the medication adherence pattern including its
      associated factors. Method Patients already diagnosed as neuropathic pain were
      interviewed using structured questionnaire and data entered in Microsoft Office
      Excel 2007. Informed consent was taken from the patients. Result Among the 84
      patients in the study, 69% were females. Majority 53.6% of patients had low back
      pain as cause of neuropathic pain. Anticonvulsants were mostly prescribed (75%)
      followed by non-steroidal anti-inflammatory drugs (52.4%) and Methylcobalamin
      (47.6%). More than 50% (n=49) patients were not adherent to the prescribed
      medication and majority (61.2%) of them were housewives. Significant association
      was observed between patient's adherence to gender, occupation, polypharmacy,
      drug regimen, cost and availability of medicine. Conclusion Anticonvulsants were
      commonly prescribed drugs in patients with neuropathic pain. Neuropathic pain was
      seen more in females with low back pain. Majority of patients were non-adherent
      and forgetfulness was the major reason for missing dose in them.

PMID- 27892442
TI  - Retrospective study of HIV infection in Anti Retroviral Treatment center of
      Mahendranagar, Nepal.
AB  - Background Being the most backward region, The Far Western Development Region has
      high illiteracy rate, low socioeconomic status and high migration rate
      contributing the progression of epidemiological status of Human Immunodeficiency
      Virus (HIV) towards generalized form. Objective To study the demographic profile
      of the HIV positive patients, along with their CD4 status and tuberculosis during
      diagnosis. Method A retrospective descriptive study carried out from May 2006 to
      July 2012 in 271 HIV patients registered in HIV clinic of Mahakali Zonal
      Hospital, Mahendranagar. Result Among 271 patients enrolled, 48.30% (131) were
      male and 51.7% (140) were females. Thirty seven (13.7%) were less than 15 years
      and 76.3% (207) were of age 16-45 years. 38.7% were household workers by
      occupation and 34.50% were involved in agriculture and 3.70%were migrant labour.
      At the time of presentation, 22.4% (60) were stage I according to WHO staging and
      18.5% (50), 58.5 (158) and 0.7% (2) were of stage II, III and IV respectively.
      Similarly, 33.0% (89) had more than 350 CD4 count at the time of presentation.
      20.8% (56) of patients were infected with tuberculosis. Among 236 families, 2 or
      more members were found to be affected in 24 families. In most of the cases,
      female were diagnosed first followed by male in the families, where both the
      couple were infected. Conclusion Most of the HIV infected patients were of
      productive age group. Majority of patients were uneducated and Tuberculosis was
      found to be common opportunistic infections associated with HIV infection.

PMID- 27892443
TI  - Medication Adherence Pattern and Factors affecting Adherence in Helicobacter
      Pylori Eradication Therapy.
AB  - Background Helicobacter pylori (H. pylori) infection is the most common chronic
      bacterial infection worldwide affecting approximately half of the world's
      population. A number of screening tests as well as complex multi-drug therapies
      are available for the detection and treatment of H. pylori infection. However,
      the optimum eradication rates of H. pylori infection can only be achieved if
      adherence to drug therapy is higher. Therefore, it is of utmost importance to
      determine the factors leading to poor adherence to obtain successful treatment
      outcomes. Objective To determine the medication adherence pattern in patients
      with H. pylori infection and assess the factors associated with non-adherence to
      the prescribed drug therapy. Method Patients meeting the inclusion criteria who
      were confirmed as H. pylori positive by rapid urease test (histopathology) and/
      or stool antigen test and those under H. pylori eradication therapy were
      considered. Informed consent was taken from the patients or from the patient
      party in incapacitated patients. They were then interviewed using structured
      questionnaire. Statistical analysis was done using SPSS version 20 and a p-value
      < 0.05 was considered as statistically significant. Result Among the 70
      participants included in this study, 57.10% (n=40) of them were males. The mean
      (+/-SD) age of the patients was 42.36 years (+/-17.93). Higher number (85.70%
      (n=60)) of the patients were adherent to the recommended medication.
      Forgetfulness was the reason for missing dose in a majority (80% (n=8)) of the
      nonadherent patients. A highly significant association (p<0.05) was observed
      between adherence and absence of symptomatic relief. However, there was no
      statistically significant association (p>0.05) between patients' adherence to
      gender, age, literacy, and the prescribed treatment regimen. Conclusion Majority
      of the patients with H. pylori infection were adherent to medication.
      Forgetfulness was the major reason for missing dose in the non-adherent patients.

PMID- 27892444
TI  - Mortality Patterns among Hospital Deaths.
AB  - Background Death occurring in hospital is medically certified by attending
      physicians with cause of death. In developing countries such as Nepal, limited
      resources are available related to the pattern of deaths that occur in hospitals,
      so that the health priorities can be selected wisely. Objective The objective of
      this study was to determine the pattern, frequency and causes of inpatient
      mortality in hospital. Method This was a retrospective study of all deaths
      occurred at the Dhulikhel Hospital, Kathmandu University Hospital, Dhulikhel from
      1st January 2012 to 31st December 2013. There were 247 deaths and for each case,
      medical records were reviewed. Result There were 26,836 patients admitted during
      the study period and 247 (0.90%) of them died in hospital. Males accounted for
      42.92% (n=106) deaths and female 57.08% (n=141). The average length of stay
      before death were less than 5 days (n=152). The majority of deaths were in
      Medicine department 52.64% (n=130) followed by Pediatrics 32.38% (n=80). Majority
      of deaths were at the extremes of life so that less than one month 12.95% (n=32)
      and over 60 years 36.84% (n=91). The main cause of death was respiratory disease
      38.87% (n=96), followed by infectious 20.64% (n=51) and hepatobiliary disease
      16.19% (n=40). Conclusion Registration data on causes for deaths occurring in
      hospitals require periodic validation prior to their use for epidemiological
      research or public health policy. Procedures for death certification and coding
      of underlying causes of death need to be streamlined to improve reliability of
      registration data. Estimation of cause-specific mortality from this research will
      inform the burden of disease and guide to intervene and reduce avoidable
      mortality in hospitals.

PMID- 27892445
TI  - Drainage versus no Drainage after Elective Laparoscopic Cholecystectomy.
AB  - Background Laparoscopic cholecystectomy is the gold standard for the surgical
      treatment of cholelithiasis. Routine drainage after elective LC is an issue of
      considerable debate. Objective To evaluate the advantages and disadvantages of
      drainage in patients undergoing Laparoscopic cholecystectomy. Method The study
      was conducted at the department of surgery in Nepalgunj Medical College and
      Teaching Hospital, Kohalpur between March 2013 and May 2014. During the period of
      study, sixty patients underwent laparoscopic cholecystectomy for symptomatic gall
      stone. Sixty patients were randomized before surgical procedure into two groups.
      Group A consisted 30 patients in whom a drain was placed in subhepatic space and
      group B consisted 30 patients without drain. Postoperative pain was assessed
      using a 10-point visual analog scale. The two groups were evaluated and compared
      regarding postoperative pain, the time needed for surgery, length of
      postoperative hospital stay and the incidence of postoperative complications.
      Result The mean operative time in group A was 6.16 minutes longer when compared
      with group B (p>0.05). Although the postoperative mean pain score was same at 6
      hours after surgery in both groups (7.53 vs 7.23), the postoperative pain was
      higher in the group A by more than two points on the average in VAS (visual
      analogue score) at 24 hours and 48 hours. The proportion of the patients staying
      in the hospital for more than two days was higher in group A, 14 (46.66%) and 8
      (26.66%) in group B (p < 0.05). There was no statistical difference in the rate
      of wound infections, shoulder pain, nausea, vomiting, and respiratory infections
      between the two groups. Conclusion The routine drainage of gallbladder bed after
      elective laparoscopic cholecystectomy may not be justified and appears to cause
      more postoperative pain and more postoperative complications and prolongs the
      hospital stay.

PMID- 27892446
TI  - Assessment of Nutritional Status of Children Under Five years of age in rural
      Nepal.
AB  - Background Nutritional status of children is one of the major predictors of child
      survival. However, malnutrition is a major public health problem in most of the
      developing countries and occurs prominently among under-five children. In context
      of Nepal, nearly 37% children are suffering from underweight, 41% from stunting
      and 11% are suffering from wasting. These children are at a substantially greater
      risk of severe acute malnutrition and death. Objective The objective of the study
      was to assess the nutritional status of children under five years of age and to
      find the factors associated with malnutrition. Method A cross-sectional study was
      conducted in Dolakha and Kavre districts of Nepal for assessing the nutritional
      status of under-five children and associated factors. A total of 243 under five
      children were included from two purposively selected village development
      committees (VDCs) i.e. one from each district. Statistical Package for the Social
      Sciences (SPSS) 22 Version and ENA Software Version 2011 were used for analyzing
      the data. Result Out of 243 children, according to WHO based on weight for height
      assessment, 17 (7.0%) were wasted, in height for age analysis, 97 (39.9%) were
      stunted and in weight for age assessment, 46 (18.9%) were underweight. Conclusion
      In the study population, there is high prevalence of malnutrition, especially
      stunting among under-five. Taking into account weight, height, age, and mid upper
      arm circumference (MUAC) measurements of malnourished children more than
      threefifths of them were found below -2SD and nearly one-fourths below -3SD which
      needs intervention.

PMID- 27892447
TI  - A Study on Variations of Nutrient Foramen of Humerus with its Clinical
      Implications.
AB  - Background Nutrient foramen is an opening into shaft of humerus which gives
      passage to the blood vessels of medullary cavity. The knowledge of nutrient
      foramen is important in surgical procedures like bone grafting and more recently
      in microsurgical vascularized bone transplantation. Objective To determine the
      number, location and direction of nutrient foramen and whether the nutrient
      foramens obey the rule of ossification, that is directed away from the growing
      end of the bone or not. Method The present study consisted of 253 (108 right and
      145 left) dried humeri excluding any fracture or pathological abnormalities
      during the period of 15th December 2014 - 14th February 2015. Number and
      direction of nutrient foramen was observed in each humerus. Location of nutrient
      foramen in relation with surfaces and zones of humeri was determined. Result It
      has been observed that 60.87% of the humeri had a single nutrient foramen, 28.85%
      double foramen, 6.32% triple foramen and 1.98% of humeri had four nutrient
      foramina where as 1.98% humeri did not have any nutrient foramina. It was
      concluded that the majority (88.86%) of the nutrient foramina were present on the
      antero-medial surface, 6.52% on the anterolateral surface and 4.62% on the
      posterior surface of the shaft of humeri. It was also concluded that most
      (94.84%) of the foramina present in the zone II followed by zone III (4.62%) then
      by zone I (0.54%). All foramina were directed toward the lower end of humeri.
      Conclusion By knowing the number and location of the nutrient foramina in humerus
      would be useful in preventing intra-operative injury of nutrient artery during
      orthopedic, plastic and reconstructive surgery and will also be relevant in
      medico legal practice.

PMID- 27892448
TI  - Acute Subperiosteal Hematoma of the Orbit with Visual Impairment: An
      Unconventional Presentation.
AB  - Acute subperiosteal hematoma of orbit is a rare condition and its presentation
      with rapid severe diminution of vision is even rarest. Urgent intervention is
      required for these patients presenting with visual compromise. Needle aspiration
      is safe and simple procedure for management of such hematoma provided the patient
      presents early and does not have any associated complications. We present one
      such rare case highlighting the importance of timely diagnosis and urgent
      management to overcome functional complications in acute subperiosteal hematoma.
      To best of our knowledge this is the first pediatric case presenting with acute
      subperiosteal hematoma accompanied by severely diminished vision within few hours
      of trauma.

PMID- 27892449
TI  - Otorrhagia and Nosebleed as first signs of Intravascular Absorption Syndrome
      During Hysteroscopy: From Bench to Bedside.
AB  - Hysteroscopic surgery is indicated for the treatment of several intrauterine
      diseases. The surgeon needs to be aware of, and know how to prevent, possible
      complications related to these procedures. In the case of operative hysteroscopy,
      the systemic effects of low-viscosity fluid uptake must be considered in order to
      prevent the complications in the patient. We report on two unusual clinical signs
      of intravascular absorption syndrome (IAS) that developed during an operative
      hysteroscopy with glycine 1.5% as the fluid of distension. Based on our
      experience, we recommend that practitioners reduce operating times, monitor fluid
      balances, check electrolytes and kinetic heart rates, and monitor for symptoms
      including otorrhagia and nosebleed, in order to identify and possibly prevent IAS
      due to an overload of low-viscosity fluids.

PMID- 27892450
TI  - Orthognathic Surgery for the Correction of Severe Skeletal Class III
      Malocclusion.
AB  - Skeletal Malocclusions results from the abnormal position of maxilla and mandible
      in relation with cranial base. These types of malocclusion are commonly treated
      by orthodontic teeth movement known as camouflage orthodontics. However severe
      skeletal malocclusions cannot be treated by orthodontics alone. Such cases need
      surgical intervention to align the position of the jaw along with orthodontic
      correction. This procedure is commonly known as Orthognathic Surgery.
      Orthognathic Surgery dates back to early eighteenth century but became popular on
      mid twentieth century. Though the prevalence of skeletal malocclusion is more
      than 1% the treatment facility was not available in Nepal till 2012. Here we
      present a case of Skeletal Class III malocclusion treated at Dhulikhel Hospital,
      Kathmandu University Hospital. For this case, double jaw surgery was performed by
      le-Fort I osteotomy and Bilateral Sagital Split Osteotomy. Orthognathic surgery
      has been routinely performed at this centre since then.

PMID- 27892451
TI  - Upregulation of (C-X-C motif) Ligand 13 (CXCL13) Attenuates Morphine Analgesia in
      Rats with Cancer-Induced Bone Pain.
AB  - BACKGROUNDThe aim of this study was to investigate the role of chemokine (C-X-C
      motif) ligand 13 (CXCL13) in morphine tolerance in rats with cancer-induced bone
      pain (CIBP).MATERIAL AND METHODSWe established a rat CIBP model and a rat CIBP
      morphine tolerance (BM) model. BM rats were intrathecally administered rmCXCL13,
      neutralizing anti-CXCL13, and normal saline, while the control group rats
      underwent a sham operation and were injected with normal saline. The morphine
      analgesia was assessed by measuring mechanical withdrawal threshold (MWT) and
      mechanical withdrawal duration (MWD) at various time points. The co-expressions
      of CXCL13 and NeuN were measured by immunofluorescence double-staining. CXCL13
      protein and mRNA expressions were detected by Western blot and quantitative real
      time polymerase chain reaction (RT-qPCR), respectively.RESULTSCompared to the
      sham-operation (S) group, the BM group showed obviously decreased MWT and
      increased MWD on Day 9 after CIBP, but obviously increased MWT and decreased MWD
      on Day 3 after morphine administration; subsequently, the MWT was decreased and
      MWD was increased (all P<0.05). In comparison with the S+saline group, increased
      MWT and decreased MWD were observed in BM rats on Day 3 after anti-CXCL13
      administration, and obviously decreased MWT and increased MWD were found in BM
      rats on Day 3 after rmCXCL13 administration (all P<0.05).CONCLUSIONSUp-regulated
      CXCL13 has a negative role in morphine analgesia in relief of CIBP, which may
      provide a new target for the management of CIBP.

PMID- 27892452
TI  - The Perfect Glass Paradigm: Disordered Hyperuniform Glasses Down to Absolute
      Zero.
AB  - Rapid cooling of liquids below a certain temperature range can result in a
      transition to glassy states. The traditional understanding of glasses includes
      their thermodynamic metastability with respect to crystals. However, here we
      present specific examples of interactions that eliminate the possibilities of
      crystalline and quasicrystalline phases, while creating mechanically stable
      amorphous glasses down to absolute zero temperature. We show that this can be
      accomplished by introducing a new ideal state of matter called a "perfect glass".
      A perfect glass represents a soft-interaction analog of the maximally random
      jammed (MRJ) packings of hard particles. These latter states can be regarded as
      the epitome of a glass since they are out of equilibrium, maximally disordered,
      hyperuniform, mechanically rigid with infinite bulk and shear moduli, and can
      never crystallize due to configuration-space trapping. Our model perfect glass
      utilizes two-, three-, and four-body soft interactions while simultaneously
      retaining the salient attributes of the MRJ state. These models constitute a
      theoretical proof of concept for perfect glasses and broaden our fundamental
      understanding of glass physics. A novel feature of equilibrium systems of
      identical particles interacting with the perfect-glass potential at positive
      temperature is that they have a non-relativistic speed of sound that is infinite.

PMID- 27892453
TI  - Topological magnetoplasmon.
AB  - Classical wave fields are real-valued, ensuring the wave states at opposite
      frequencies and momenta to be inherently identical. Such a particle-hole symmetry
      can open up new possibilities for topological phenomena in classical systems.
      Here we show that the historically studied two-dimensional (2D) magnetoplasmon,
      which bears gapped bulk states and gapless one-way edge states near-zero
      frequency, is topologically analogous to the 2D topological p+ip superconductor
      with chiral Majorana edge states and zero modes. We further predict a new type of
      one-way edge magnetoplasmon at the interface of opposite magnetic domains, and
      demonstrate the existence of zero-frequency modes bounded at the peripheries of a
      hollow disk. These findings can be readily verified in experiment, and can
      greatly enrich the topological phases in bosonic and classical systems.

PMID- 27892454
TI  - Miniature optical planar camera based on a wide-angle metasurface doublet
      corrected for monochromatic aberrations.
AB  - Optical metasurfaces are two-dimensional arrays of nano-scatterers that modify
      optical wavefronts at subwavelength spatial resolution. They are poised to
      revolutionize optics by enabling complex low-cost systems where multiple
      metasurfaces are lithographically stacked and integrated with electronics. For
      imaging applications, metasurface stacks can perform sophisticated image
      corrections and can be directly integrated with image sensors. Here we
      demonstrate this concept with a miniature flat camera integrating a monolithic
      metasurface lens doublet corrected for monochromatic aberrations, and an image
      sensor. The doublet lens, which acts as a fisheye photographic objective, has a
      small f-number of 0.9, an angle-of-view larger than 60 degrees  * 60 degrees ,
      and operates at 850 nm wavelength with 70% focusing efficiency. The camera
      exhibits nearly diffraction-limited image quality, which indicates the potential
      of this technology in the development of optical systems for microscopy,
      photography, and computer vision.

PMID- 27892455
TI  - Selective suppression of antisense transcription by Set2-mediated H3K36
      methylation.
AB  - Maintenance of a regular chromatin structure over the coding regions of genes
      occurs co-transcriptionally via the 'chromatin resetting' pathway. One of the
      central players in this pathway is the histone methyltransferase Set2. Here we
      show that the loss of Set2 in yeast, Saccharomyces cerevisiae, results in
      transcription initiation of antisense RNAs embedded within body of protein-coding
      genes. These RNAs are distinct from the previously identified non-coding RNAs and
      cover 11% of the yeast genome. These RNA species have been named Set2-repressed
      antisense transcripts (SRATs) since the co-transcriptional addition of the H3K36
      methyl mark by Set2 over their start sites results in their suppression.
      Interestingly, loss of chromatin resetting factor Set2 or the subsequent
      production of SRATs does not affect the abundance of the sense transcripts. This
      difference in transcriptional outcomes of overlapping transcripts due to a strand
      independent addition of H3K36 methylation is a key regulatory feature of
      interleaved transcriptomes.

PMID- 27892456
TI  - IL-12 protects from psoriasiform skin inflammation.
AB  - Neutralization of the common p40-subunit of IL-12/23 in psoriasis patients has
      led to a breakthrough in the management of moderate to severe disease. Aside from
      neutralizing IL-23, which is thought to be responsible for the curative effect,
      anti-p40 therapy also interferes with IL-12 signalling and type 1 immunity. Here
      we dissect the individual contribution of these two cytokines to the formation of
      psoriatic lesions and understand the effect of therapeutic co-targeting of IL-12
      and IL-23 in psoriasis. Using a preclinical model for psoriatic plaque formation
      we show that IL-12, in contrast to IL-23, has a regulatory function by
      restraining the invasion of an IL-17-committed gammadeltaT (gammadeltaT17) cell
      subset. We discover that IL-12 receptor signalling in keratinocytes initiates a
      protective transcriptional programme that limits skin inflammation, suggesting
      that collateral targeting of IL-12 by anti-p40 monoclonal antibodies is
      counterproductive in the therapy of psoriasis.

PMID- 27892459
TI  - Borane catalysed ring opening and closing cascades of furans leading to silicon
      functionalized synthetic intermediates.
AB  - The conversion of renewable biomass resources to synthetically valuable chemicals
      is highly desirable, but remains a formidable challenge in regards to the
      substrate scope and reaction conditions. Here we present the development of
      tris(pentafluorophenyl)borane-catalysed conversion of furans via ring-opening and
      closing cascade processes to afford silicon-functionalized synthetic chemicals
      under transition metal-free conditions. The furan ring-opening with hydrosilanes
      is highly efficient (TON up to 2,000) and atom-economical without forming any
      byproduct to give rise to alpha-silyloxy-(Z)-alkenyl silanes. Additional
      equivalents of silane smoothly induce a subsequent B(C6F5)3-catalysed cyclization
      of initially formed olefinic silane compounds to produce anti-(2
      alkyl)cyclopropyl silanes, another versatile synthon being potentially applicable
      in the synthesis of natural products and pharmacophores.

PMID- 27892457
TI  - Amplification of USP13 drives ovarian cancer metabolism.
AB  - Dysregulated energetic metabolism has been recently identified as a hallmark of
      cancer. Although mutations in metabolic enzymes hardwire metabolism to
      tumourigenesis, they are relatively infrequent in ovarian cancer. More often,
      cancer metabolism is re-engineered by altered abundance and activity of the
      metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a
      master regulator that drives ovarian cancer metabolism. USP13 specifically
      deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate
      dehydrogenase, two key enzymes that determine mitochondrial respiration,
      glutaminolysis and fatty acid synthesis. The USP13 gene is co-amplified with
      PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is
      significantly associated with poor clinical outcome. Inhibiting USP13 remarkably
      suppresses ovarian tumour progression and sensitizes tumour cells to the
      treatment of PI3K/AKT inhibitor. Our results reveal an important metabolism
      centric role of USP13, which may lead to potential therapeutics targeting USP13
      in ovarian cancers.

PMID- 27892460
TI  - Superstrength of nanograined steel with nanoscale intermetallic precipitates
      transformed from shock-compressed martensitic steel.
AB  - An increasing number of industrial applications need superstrength steels. It is
      known that refined grains and nanoscale precipitates can increase strength. The
      hardest martensitic steel reported to date is C0.8 steel, whose nanohardness can
      reach 11.9 GPa through incremental interstitial solid solution strengthening.
      Here we report a nanograined (NG) steel dispersed with nanoscale precipitates
      which has an extraordinarily high hardness of 19.1 GPa. The NG steel (shock
      compressed Armox 500T steel) was obtained under these conditions: high strain
      rate of 1.2 MUs-1, high temperature rise rate of 600 KMUs-1 and high pressure of
      17 GPa. The mean grain size achieved was 39 nm and reinforcing precipitates were
      indexed in the NG steel. The strength of the NG steel is expected to be ~3950
      MPa. The discovery of the NG steel offers a general pathway for designing new
      advanced steel materials with exceptional hardness and excellent strength.

PMID- 27892458
TI  - Modulation of mRNA and lncRNA expression dynamics by the Set2-Rpd3S pathway.
AB  - H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed
      regions of mRNA genes, repressing internal cryptic promoters and slowing
      elongation. Here we explore the function of this pathway by analysing
      transcription in yeast undergoing a series of carbon source shifts. Approximately
      80 mRNA genes show increased induction upon SET2 deletion. A majority of these
      promoters have overlapping lncRNA transcription that targets H3K36me3 and
      deacetylation by Rpd3S to the mRNA promoter. We previously reported a similar
      mechanism for H3K4me2-mediated repression via recruitment of the Set3C histone
      deacetylase. Here we show that the distance between an mRNA and overlapping
      lncRNA promoter determines whether Set2-Rpd3S or Set3C represses. This analysis
      also reveals many previously unreported cryptic ncRNAs induced by specific carbon
      sources, showing that cryptic promoters can be environmentally regulated.
      Therefore, in addition to repression of cryptic transcription and modulation of
      elongation, H3K36 methylation maintains optimal expression dynamics of many mRNAs
      and ncRNAs.

PMID- 27892463
TI  - Reconfigurable exciton-plasmon interconversion for nanophotonic circuits.
AB  - The recent challenges for improving the operation speed of nanoelectronics have
      motivated research on manipulating light in on-chip integrated circuits. Hybrid
      plasmonic waveguides with low-dimensional semiconductors, including quantum dots
      and quantum wells, are a promising platform for realizing sub-diffraction limited
      optical components. Meanwhile, two-dimensional transition metal dichalcogenides
      (TMDs) have received broad interest in optoelectronics owing to tightly bound
      excitons at room temperature, strong light-matter and exciton-plasmon
      interactions, available top-down wafer-scale integration, and band-gap
      tunability. Here, we demonstrate principal functionalities for on-chip optical
      communications via reconfigurable exciton-plasmon interconversions in ~200-nm
      diameter Ag-nanowires overlapping onto TMD transistors. By varying device
      configurations for each operation purpose, three active components for optical
      communications are realized: field-effect exciton transistors with a channel
      length of ~32 MUm, field-effect exciton multiplexers transmitting multiple
      signals through a single NW and electrical detectors of propagating plasmons with
      a high On/Off ratio of~190. Our results illustrate the unique merits of two
      dimensional semiconductors for constructing reconfigurable device architectures
      in integrated nanophotonic circuits.

PMID- 27892462
TI  - Unraveling the Planar-Globular Transition in Gold Nanoclusters through
      Evolutionary Search.
AB  - Au nanoclusters are of technological relevance for catalysis, photonics, sensors,
      and of fundamental scientific interest owing to planar to globular structural
      transformation at an anomalously high number of atoms i.e. in the range 12-14.
      The nature and causes of this transition remain a mystery. In order to unravel
      this conundrum, high throughput density functional theory (DFT) calculations,
      coupled with a global structural optimization scheme based on a modified genetic
      algorithm (GA) are conducted. More than 20,000 Au12, Au13, and Au14 nanoclusters
      are evaluated. With any DFT functional, globular and planar structures coexist
      across the size range of interest. The planar-globular transition is gradual at
      room temperature rather than a sharp transition as previously believed. The
      effects of anionicity, s-d band hybridization and long range interactions on the
      dimensional transition are quantified by using the structures adjacent to the
      minima. Anionicity marginally changes the relative stability of the clusters. The
      degree of s-d hybridization is varied via changing the Hubbard U value which
      corroborate that s-d hybridization alone does not stabilize planar structures.
      van der Waals interactions, on the other hand, stabilize globular structures.
      These results elucidate the balance between the different reasons of the
      dimensional transition in gold nanoclusters.

PMID- 27892461
TI  - Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and
      attenuates atherosclerosis.
AB  - Despite widespread use of statins to reduce low-density lipoprotein cholesterol
      (LDL-C) and associated atherosclerotic cardiovascular risk, many patients do not
      achieve sufficient LDL-C lowering due to muscle-related side effects, indicating
      novel treatment strategies are required. Bempedoic acid (ETC-1002) is a small
      molecule intended to lower LDL-C in hypercholesterolemic patients, and has been
      previously shown to modulate both ATP-citrate lyase (ACL) and AMP-activated
      protein kinase (AMPK) activity in rodents. However, its mechanism for LDL-C
      lowering, efficacy in models of atherosclerosis and relevance in humans are
      unknown. Here we show that ETC-1002 is a prodrug that requires activation by very
      long-chain acyl-CoA synthetase-1 (ACSVL1) to modulate both targets, and that
      inhibition of ACL leads to LDL receptor upregulation, decreased LDL-C and
      attenuation of atherosclerosis, independently of AMPK. Furthermore, we
      demonstrate that the absence of ACSVL1 in skeletal muscle provides a mechanistic
      basis for ETC-1002 to potentially avoid the myotoxicity associated with statin
      therapy.

PMID- 27892466
TI  - Direct evidence for microbial-derived soil organic matter formation and its
      ecophysiological controls.
AB  - Soil organic matter (SOM) and the carbon and nutrients therein drive fundamental
      submicron- to global-scale biogeochemical processes and influence carbon-climate
      feedbacks. Consensus is emerging that microbial materials are an important
      constituent of stable SOM, and new conceptual and quantitative SOM models are
      rapidly incorporating this view. However, direct evidence demonstrating that
      microbial residues account for the chemistry, stability and abundance of SOM is
      still lacking. Further, emerging models emphasize the stabilization of microbial
      derived SOM by abiotic mechanisms, while the effects of microbial physiology on
      microbial residue production remain unclear. Here we provide the first direct
      evidence that soil microbes produce chemically diverse, stable SOM. We show that
      SOM accumulation is driven by distinct microbial communities more so than clay
      mineralogy, where microbial-derived SOM accumulation is greatest in soils with
      higher fungal abundances and more efficient microbial biomass production.

PMID- 27892464
TI  - Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway.
AB  - Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective
      urine concentration mechanisms in the kidney, which are mainly caused by loss-of
      function mutations in the vasopressin type 2 receptor. For the treatment of
      heritable NDI, novel strategies that bypass the defective vasopressin type 2
      receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we
      show that Wnt5a regulates AQP2 protein expression, phosphorylation and
      trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2
      without the activation of the classic vasopressin/cAMP signalling pathway. Wnt5a
      successfully increases the apical membrane localization of AQP2 and urine
      osmolality in an NDI mouse model. We also demonstrate that calcineurin is a key
      regulator of Wnt5a-induced AQP2 activation without affecting intracellular cAMP
      level and PKA activity. The importance of calcineurin is further confirmed with
      its activator, arachidonic acid, which shows vasopressin-like effects underlining
      that calcineurin activators may be potential therapeutic targets for heritable
      NDI.

PMID- 27892465
TI  - Distinct role of IL-1beta in instigating disease in Sharpincpdm mice.
AB  - Mice deficient in SHARPIN (Sharpincpdm mice), a member of linear ubiquitin chain
      assembly complex (LUBAC), develop severe dermatitis associated with systemic
      inflammation. Previous studies have demonstrated that components of the TNF
      signaling pathway, NLRP3 inflammasome and IL-1R signaling are required to provoke
      skin inflammation in Sharpincpdm mice. However, whether IL-1alpha or IL-1beta,
      both of which signals through IL-1R, instigates skin inflammation and systemic
      disease is not known. Here, we have performed extensive cellular analysis of pre
      diseased and diseased Sharpincpdm mice and demonstrated that cellular
      dysregulation precedes skin inflammation. Furthermore, we demonstrate a specific
      role for IL-1beta, but not IL-1alpha, in instigating dermatitis in Sharpincpdm
      mice. Our results altogether demonstrate distinct roles of SHARPIN in initiating
      systemic inflammation and dermatitis. Furthermore, skin inflammation in
      Sharpincpdm mice is specifically modulated by IL-1beta, highlighting the
      importance of specific targeted therapies in the IL-1 signaling blockade.

PMID- 27892469
TI  - Total synthesis of feglymycin based on a linear/convergent hybrid approach using
      micro-flow amide bond formation.
AB  - Feglymycin is a naturally occurring, anti-HIV and antimicrobial 13-mer peptide
      that includes highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Here we
      describe the total synthesis of feglymycin based on a linear/convergent hybrid
      approach. Our originally developed micro-flow amide bond formation enabled highly
      racemizable peptide chain elongation based on a linear approach that was
      previously considered impossible. Our developed approach will enable the
      practical preparation of biologically active oligopeptides that contain highly
      racemizable amino acids, which are attractive drug candidates.

PMID- 27892467
TI  - Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between
      Polycomb complexes PRC1 and PRC2.
AB  - The Polycomb repressive complexes PRC1 and PRC2 play a central role in
      developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify
      chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3
      lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between
      these modifications is critical for the formation of stable Polycomb domains at
      target gene loci. While the molecular mechanism for recognition of H3K27me3 by
      PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly
      understood. Here we demonstrate a critical role for the PRC2 cofactor Jarid2 in
      mediating the interaction of PRC2 with H2AK119u1. We identify a ubiquitin
      interaction motif at the amino-terminus of Jarid2, and demonstrate that this
      domain facilitates PRC2 localization to H2AK119u1 both in vivo and in vitro. Our
      findings ascribe a critical function to Jarid2 and define a key mechanism that
      links PRC1 and PRC2 in the establishment of Polycomb domains.

PMID- 27892468
TI  - Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and
      extends C. elegans lifespan.
AB  - Human embryonic stem cells can replicate indefinitely while maintaining their
      undifferentiated state and, therefore, are immortal in culture. This capacity may
      demand avoidance of any imbalance in protein homeostasis (proteostasis) that
      would otherwise compromise stem cell identity. Here we show that human
      pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a
      chaperonin that facilitates the folding of 10% of the proteome. We find that
      ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT
      assembly. Moreover, increased TRiC/CCT complex is required to avoid aggregation
      of mutant Huntingtin protein. We further show that increased expression of CCT8
      in somatic tissues extends Caenorhabditis elegans lifespan in a TRiC/CCT
      dependent manner. Ectopic expression of CCT8 also ameliorates the age-associated
      demise of proteostasis and corrects proteostatic deficiencies in worm models of
      Huntington's disease. Our results suggest proteostasis is a common principle that
      links organismal longevity with hESC immortality.

PMID- 27892470
TI  - Vertical Magnetic Separation of Circulating Tumor Cells for Somatic Genomic
      Alteration Analysis in Lung Cancer Patients.
AB  - Efficient isolation and genetic analysis of circulating tumor cells (CTCs) from
      cancer patients' blood is a critical step for clinical applications using CTCs.
      Here, we report a novel CTC-isolation method and subsequent genetic analysis.
      CTCs from the blood were complexed with magnetic beads coated with antibodies
      against the epithelial cell adhesion molecule (EpCAM) and separated vertically on
      a density-gradient medium in a modified well-plate. The recovery rate of model
      CTCs was reasonable and the cell purity was enhanced dramatically when compared
      to those parameters obtained using a conventional magnetic isolation method. CTCs
      were recovered from an increased number of patient samples using our magnetic
      system vs. the FDA-approved CellSearch system (100% vs. 33%, respectively). In 8
      of 13 cases, targeted deep sequencing analysis of CTCs revealed private point
      mutations present in CTCs but not in matched tumor samples and white blood cells
      (WBCs), which was also validated by droplet digital PCR. Copy-number alterations
      in CTCs were also observed in the corresponding tumor tissues for some patients.
      In this report, we showed that CTCs isolated by the EpCAM-based method had
      complex and diverse genetic features that were similar to those of tumor samples
      in some, but not all, cases.

PMID- 27892473
TI  - Narrowing the spread in CMIP5 model projections of air-sea CO2 fluxes.
AB  - Large spread appears in the projection of air-sea CO2 fluxes using the latest
      simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5). Here,
      two methods are applied to narrow this spread in 13 CMIP5 models. One method
      involves model selection based on the ability of models to reproduce the observed
      air-sea CO2 fluxes from 1980 to 2005. The other method involves constrained
      estimation based on the strong relationship between the historical and future air
      sea CO2 fluxes. The estimated spread of the projected air-sea CO2 fluxes is
      effectively reduced by using these two approaches. These two approaches also show
      great agreement in the global ocean and three regional oceans of the equatorial
      Pacific Ocean, the North Atlantic Ocean and the Southern Ocean, including the
      average state and evolution characteristics. Based on the projections of the two
      approaches, the global ocean carbon uptake will increase in the first half of the
      21st century then remain relatively stable and is projected to be 3.68-4.57
      PgC/yr at the end of 21st century. The projections indicate that the increase in
      the CO2 uptake by the oceans will cease at the year of approximately 2070.

PMID- 27892471
TI  - Combining Multiple Hypothesis Testing with Machine Learning Increases the
      Statistical Power of Genome-wide Association Studies.
AB  - The standard approach to the analysis of genome-wide association studies (GWAS)
      is based on testing each position in the genome individually for statistical
      significance of its association with the phenotype under investigation. To
      improve the analysis of GWAS, we propose a combination of machine learning and
      statistical testing that takes correlation structures within the set of SNPs
      under investigation in a mathematically well-controlled manner into account. The
      novel two-step algorithm, COMBI, first trains a support vector machine to
      determine a subset of candidate SNPs and then performs hypothesis tests for these
      SNPs together with an adequate threshold correction. Applying COMBI to data from
      a WTCCC study (2007) and measuring performance as replication by independent GWAS
      published within the 2008-2015 period, we show that our method outperforms
      ordinary raw p-value thresholding as well as other state-of-the-art methods.
      COMBI presents higher power and precision than the examined alternatives while
      yielding fewer false (i.e. non-replicated) and more true (i.e. replicated)
      discoveries when its results are validated on later GWAS studies. More than 80%
      of the discoveries made by COMBI upon WTCCC data have been validated by
      independent studies. Implementations of the COMBI method are available as a part
      of the GWASpi toolbox 2.0.

PMID- 27892472
TI  - Atomistic characterization of the active-site solvation dynamics of a model
      photocatalyst.
AB  - The interactions between the reactive excited state of molecular photocatalysts
      and surrounding solvent dictate reaction mechanisms and pathways, but are not
      readily accessible to conventional optical spectroscopic techniques. Here we
      report an investigation of the structural and solvation dynamics following
      excitation of a model photocatalytic molecular system [Ir2(dimen)4]2+, where
      dimen is para-diisocyanomenthane. The time-dependent structural changes in this
      model photocatalyst, as well as the changes in the solvation shell structure,
      have been measured with ultrafast diffuse X-ray scattering and simulated with
      Born-Oppenheimer Molecular Dynamics. Both methods provide direct access to the
      solute-solvent pair distribution function, enabling the solvation dynamics around
      the catalytically active iridium sites to be robustly characterized. Our results
      provide evidence for the coordination of the iridium atoms by the acetonitrile
      solvent and demonstrate the viability of using diffuse X-ray scattering at free
      electron laser sources for studying the dynamics of photocatalysis.

PMID- 27892474
TI  - Caterpillar-induced plant volatiles attract conspecific adults in nature.
AB  - Plants release volatiles in response to caterpillar feeding that attract natural
      enemies of the herbivores, a tri-trophic interaction which has been considered an
      indirect plant defence against herbivores. The caterpillar-induced plant
      volatiles have been reported to repel or attract conspecific adult herbivores. To
      date however, no volatile signals that either repel or attract conspecific adults
      under field conditions have been chemically identified. Apple seedlings uniquely
      released seven compounds including acetic acid, acetic anhydride, benzyl alcohol,
      benzyl nitrile, indole, 2-phenylethanol, and (E)-nerolidol only when infested by
      larvae of the light brown apple moth, Epiphyas postvittana. In field tests in New
      Zealand, a blend of two of these, benzyl nitrile and acetic acid, attracted a
      large number of conspecific male and female adult moths. In North America, male
      and female adults of the tortricid, oblique-banded leafroller, Choristoneura
      rosaceana, were most attracted to a blend of 2-phenylethanol and acetic acid.
      Both sexes of the eye-spotted bud moth, Spilonota ocellana, were highly attracted
      to a blend of benzyl nitrile and acetic acid. This study provides the first
      identification of caterpillar-induced plant volatiles that attract conspecific
      adult herbivores under natural conditions, challenging the expectation of
      herbivore avoidance of these induced volatiles.

PMID- 27892475
TI  - Droplet Merging on a Lab-on-a-Chip Platform by Uniform Magnetic Fields.
AB  - Droplet microfluidics offers a range of Lab-on-a-chip (LoC) applications.
      However, wireless and programmable manipulation of such droplets is a challenge.
      We address this challenge by experimental and modelling studies of uniform
      magnetic field induced merging of ferrofluid based droplets. Control of droplet
      velocity and merging was achieved through uniform magnetic field and flow rate
      ratio. Conditions for droplet merging with respect to droplet velocity were
      studied. Merging and mixing of colour dye + magnetite composite droplets was
      demonstrated. Our experimental and numerical results are in good agreement. These
      studies are useful for wireless and programmable droplet merging as well as
      mixing relevant to biosensing, bioassay, microfluidic-based synthesis, reaction
      kinetics, and magnetochemistry.

PMID- 27892476
TI  - Comparative transcriptome analysis between an evolved abscisic acid-overproducing
      mutant Botrytis cinerea TBC-A and its ancestral strain Botrytis cinerea TBC-6.
AB  - Abscisic acid (ABA) is a classical phytohormone which plays an important role in
      plant stress resistance. Moreover, ABA is also found to regulate the activation
      of innate immune cells and glucose homeostasis in mammals. Therefore, this
      'stress hormone' is of great importance to theoretical research and agricultural
      and medical applications. Botrytis cinerea is a well-known phytopathogenic
      ascomycete that synthesizes ABA via a pathway substantially different from higher
      plants. Identification of the functional genes involved in ABA biosynthesis in B.
      cinerea would be of special interest. We developed an ABA-overproducing mutant
      strain, B. cinerea TBC-A, previously and obtained a 41.5-Mb genome sequence of B.
      cinerea TBC-A. In this study, the transcriptomes of B. cinerea TBC-A and its
      ancestral strain TBC-6 were sequenced under identical fermentation conditions. A
      stringent comparative transcriptome analysis was performed to identify
      differentially expressed genes participating in the metabolic pathways related to
      ABA biosynthesis in B. cinerea. This study provides the first global view of the
      transcriptional changes underlying the very different ABA productivity of the B.
      cinerea strains and will expand our knowledge of the molecular basis for ABA
      biosynthesis in B. cinerea.

PMID- 27892477
TI  - Nanomolar oligomerization and selective co-aggregation of alpha-synuclein
      pathogenic mutants revealed by single-molecule fluorescence.
AB  - Protein aggregation is a hallmark of many neurodegenerative diseases, notably
      Alzheimer's and Parkinson's disease. Parkinson's disease is characterized by the
      presence of Lewy bodies, abnormal aggregates mainly composed of alpha-synuclein.
      Moreover, cases of familial Parkinson's disease have been linked to mutations in
      alpha-synuclein. In this study, we compared the behavior of wild-type (WT) alpha
      synuclein and five of its pathological mutants (A30P, E46K, H50Q, G51D and A53T).
      To this end, single-molecule fluorescence detection was coupled to cell-free
      protein expression to measure precisely the oligomerization of proteins without
      purification, denaturation or labelling steps. In these conditions, we could
      detect the formation of oligomeric and pre-fibrillar species at very short time
      scale and low micromolar concentrations. The pathogenic mutants surprisingly
      segregated into two classes: one group forming large aggregates and fibrils while
      the other tending to form mostly oligomers. Strikingly, co-expression experiments
      reveal that members from the different groups do not generally interact with each
      other, both at the fibril and monomer levels. Together, this data paints a
      completely different picture of alpha-synuclein aggregation, with two possible
      pathways leading to the development of fibrils.

PMID- 27892478
TI  - Continuous single cell imaging reveals sequential steps of plasmacytoid dendritic
      cell development from common dendritic cell progenitors.
AB  - Functionally distinct plasmacytoid and conventional dendritic cells (pDC and cDC)
      shape innate and adaptive immunity. They are derived from common dendritic cell
      progenitors (CDPs) in the murine bone marrow, which give rise to CD11c+ MHCII-
      precursors with early commitment to DC subpopulations. In this study, we dissect
      pDC development from CDP into an ordered sequence of differentiation events by
      monitoring the expression of CD11c, MHC class II, Siglec H and CCR9 in CDP
      cultures by continuous single cell imaging and tracking. Analysis of CDP
      genealogies revealed a stepwise differentiation of CDPs into pDCs in a part of
      the CDP colonies. This developmental pathway involved an early CD11c+ SiglecH-
      pre-DC stage and a Siglec H+ CCR9low precursor stage, which was followed rapidly
      by upregulation of CCR9 indicating final pDC differentiation. In the majority of
      the remaining CDP pedigrees however the Siglec H+ CCR9low precursor state was
      maintained for several generations. Thus, although a fraction of CDPs transits
      through precursor stages rapidly to give rise to a first wave of pDCs, the
      majority of CDP progeny differentiate more slowly and give rise to longer lived
      precursor cells which are poised to differentiate on demand.

PMID- 27892479
TI  - Evaluation of the Effects of Conjunctivochalasis Excision on Tear Stability and
      Contrast Sensitivity.
AB  - Conjunctivochalasis (CCh) disrupts tear flow and damages tear film stability.
      This study sought to evaluate the tear stability and contrast sensitivity of
      patients with CCh on whom CCh excision was performed. The study included 39 eyes
      from 39 patients; all patients had eyes with grade 2 or 3 CCh, underwent CCh
      excision, and were evaluated before and three months after the surgery. The
      evaluated variables included the ocular surface disease index (OSDI), the tear
      break-up time (TBUT), corneal fluorescein staining, corneal surface irregularity,
      Schirmer's I test, the tear meniscus area (TMA), and contrast sensitivity. A
      follow-up of three months was achieved in 36 eyes for 36 patients. All parameters
      improved significantly after surgery (p < 0.05), except Schirmer's I test, thus
      suggesting that CCh excision is an effective method for reconstructing the lower
      tear meniscus and improving both tear film stability and corneal surface
      irregularity. The results further demonstrated a simultaneous increase in
      contrast sensitivity after surgery.

PMID- 27892480
TI  - Metabolic response induced by parasitic plant-fungus interactions hinder amino
      sugar and nucleotide sugar metabolism in the host.
AB  - Infestation by the biotrophic pathogen Gymnosporangium asiaticum can be
      devastating for plant of the family Rosaceae. However, the phytopathology of this
      process has not been thoroughly elucidated. Using a metabolomics approach, we
      discovered the intrinsic activities that induce disease symptoms after fungal
      invasion in terms of microbe-induced metabolic responses. Through metabolic
      pathway enrichment and mapping, we found that the host altered its metabolite
      levels, resulting in accumulation of tetrose and pentose sugar alcohols, in
      response to this fungus. We then used a multiple linear regression model to
      evaluate the effect of the interaction between this abnormal accumulation of
      sugar alcohol and the group variable (control/parasitism). The results revealed
      that this accumulation resulted in deficiency in the supply of specific sugars,
      which led to a lack of amino sugar and nucleotide sugar metabolism. Halting this
      metabolism could hamper pivotal functions in the plant host, including cell wall
      synthesis and lesion repair. In conclusion, our findings indicate that altered
      metabolic responses that occur during fungal parasitism can cause deficiency in
      substrates in pivotal pathways and thereby trigger pathological symptoms.

PMID- 27892482
TI  - Coexistence of superconductivity and ferromagnetism in Sr0.5Ce0.5FBiS2-xSex (x =
      0.5 and 1.0), a non-U material with Tc < TFM.
AB  - We have carried out detailed magnetic and transport studies of the new
      Sr0.5Ce0.5FBiS2-xSex (0.0 <= x <= 1.0) superconductors derived by doping Se in
      Sr0.5Ce0.5FBiS2. Se-doping produces several effects: it suppresses semiconducting
      like behavior observed in the undoped Sr0.5Ce0.5FBiS2, the ferromagnetic ordering
      temperature, TFM, decreases considerably from 7.5 K (in Sr0.5Ce0.5FBiS2) to 3.5 K
      and the superconducting transition temperature, Tc, gets enhanced slightly to 2.9
      3.3 K. Thus in these Se-doped materials, TFM is marginally higher than Tc.
      Magnetization studies provide evidence of bulk superconductivity in
      Sr0.5Ce0.5FBiS2-xSex at x >= 0.5 in contrast to the undoped Sr0.5Ce0.5FBiS2 (x =
      0) where magnetization measurements indicate a small superconducting volume
      fraction. Quite remarkably, as compared with the effective paramagnetic Ce-moment
      (~2.2 MUB), the ferromagnetically ordered Ce-moment in the superconducting state
      is rather small (~0.1 MUB) suggesting itinerant ferromagnetism. To the best of
      our knowledge, Sr0.5Ce0.5FBiS2-x Sex (x = 0.5 and 1.0) are distinctive Ce-based
      bulk superconducting itinerant ferromagnetic materials with Tc < TFM.
      Furthermore, a novel feature of these materials is that they exhibit a dual and
      quite unusual hysteresis loop corresponding to both the ferromagnetism and the
      coexisting bulk superconductivity.

PMID- 27892481
TI  - Autophagy is required for PDAC glutamine metabolism.
AB  - Macroautophagy (autophagy) is believed to maintain energy homeostasis by
      degrading unnecessary cellular components and molecules. Its implication in
      regulating cancer metabolism recently started to be uncovered. However, the
      precise roles of autophagy in cancer metabolism are still unclear. Here, we show
      that autophagy plays a critical role in glutamine metabolism, which is required
      for tumor survival. Pancreatic ductal adenocarcinoma (PDAC) cells require both
      autophagy and typical glutamine transporters to maintain intracellular glutamine
      levels. Glutamine deprivation, but not that of glucose, led to the activation of
      macropinocytosis-associated autophagy through TFEB induction and translocation
      into the nucleus. In contrast, glutamine uptake increased as a compensatory
      response to decreased intracellular glutamine levels upon autophagy inhibition.
      Moreover, autophagy inhibition and glutamine deprivation did not induce cell
      death, while glutamine deprivation dramatically activated apoptotic cell death
      upon autophagy inhibition. Interestingly, the addition of alpha-ketoglutarate
      significantly rescued the apoptotic cell death caused by the combination of the
      inhibition of autophagy with glutamine deprivation. Our data suggest that
      macropinocytosis-associated autophagy is a critical process providing glutamine
      for anaplerosis of the TCA cycle in PDAC. Thus, targeting both autophagy and
      glutamine metabolism to completely block glutamine supply may provide new
      therapeutic approaches to treat refractory tumors.

PMID- 27892485
TI  - Isotope effect in superconducting n-doped SrTiO3.
AB  - We report the influence on the superconducting critical temperature Tc in doped
      SrTiO3 of the substitution of the natural 16O atoms by the heavier isotope 18O.
      We observe that for a wide range of doping this substitution causes a strong
      (~50%) enhancement of Tc. Also the magnetic critical field Hc2 is increased by a
      factor ~2. Such a strong impact on Tc and Hc2, with a sign opposite to
      conventional superconductors, is unprecedented. The observed effect could be the
      consequence of strong coupling of the doped electrons to lattice vibrations
      (phonons), a notion which finds support in numerous optical and photo-emission
      studies. The unusually large size of the observed isotope effect supports a
      recent model for superconductivity in these materials based on strong coupling to
      the ferroelectric soft modes of SrTiO3.

PMID- 27892484
TI  - Environmental factors linked to depression vulnerability are associated with
      altered cerebellar resting-state synchronization.
AB  - Hosting nearly eighty percent of all human neurons, the cerebellum is
      functionally connected to large regions of the brain. Accumulating data suggest
      that some cerebellar resting-state alterations may constitute a key candidate
      mechanism for depressive psychopathology. While there is some evidence linking
      cerebellar function and depression, two topics remain largely unexplored. First,
      the genetic or environmental roots of this putative association have not been
      elicited. Secondly, while different mathematical representations of resting-state
      fMRI patterns can embed diverse information of relevance for health and disease,
      many of them have not been studied in detail regarding the cerebellum and
      depression. Here, high-resolution fMRI scans were examined to estimate functional
      connectivity patterns across twenty-six cerebellar regions in a sample of 48
      identical twins (24 pairs) informative for depression liability. A network-based
      statistic approach was employed to analyze cerebellar functional networks built
      using three methods: the conventional approach of filtered BOLD fMRI time-series,
      and two analytic components of this oscillatory activity (amplitude envelope and
      instantaneous phase). The findings indicate that some environmental factors may
      lead to depression vulnerability through alterations of the neural oscillatory
      activity of the cerebellum during resting-state. These effects may be observed
      particularly when exploring the amplitude envelope of fMRI oscillations.

PMID- 27892483
TI  - Down-regulation of coasy, the gene associated with NBIA-VI, reduces Bmp
      signaling, perturbs dorso-ventral patterning and alters neuronal development in
      zebrafish.
AB  - Mutations in Pantothenate kinase 2 and Coenzyme A (CoA) synthase (COASY), genes
      involved in CoA biosynthesis, are associated with rare neurodegenerative
      disorders with brain iron accumulation. We showed that zebrafish pank2 gene plays
      an essential role in brain and vasculature development. Now we extended our study
      to coasy. The gene has high level of sequence identity with the human ortholog
      and is ubiquitously expressed from the earliest stages of development. The
      abrogation of its expression led to strong reduction of CoA content, high
      lethality and a phenotype resembling to that of dorsalized mutants. Lower doses
      of morpholino resulted in a milder phenotype, with evident perturbation in
      neurogenesis and formation of vascular arborization; the dorso-ventral patterning
      was severely affected, the expression of bone morphogenetic protein (Bmp)
      receptors and activity were decreased, while cell death increased. These features
      specifically correlated with the block in CoA biosynthesis and were rescued by
      the addition of CoA to fish water and the overexpression of the human wild-type,
      but not mutant gene. These results confirm the absolute requirement for adequate
      levels of CoA for proper neural and vascular development in zebrafish and point
      to the Bmp pathway as a possible molecular connection underlining the observed
      phenotype.

PMID- 27892486
TI  - Short Chain Fatty Acids Prevent High-fat-diet-induced Obesity in Mice by
      Regulating G Protein-coupled Receptors and Gut Microbiota.
AB  - Elucidating the mechanisms by which short chain fatty acids (SCFA) reduce body
      weight may assist in the development of an effective weight control strategy.
      Dietary supplementation of acetate, propionate, butyrate or their admixture was
      shown to significantly inhibit the body weight gain induced by high-fat diet
      feeding. Supplementation of SCFAs caused significant changes in the expressions
      of G-protein coupled receptor 43 (GPR43) and GPR41 characterized by increases in
      the adipose tissue and reductions in the colon. Additionally, they influenced the
      bacterial community structure in feces, with a reduction in the proportion of
      Firmicutes and an increase in the proportion of Bacteroidetes. The effects of
      dietary SCFAs on the GPR expression and gut microbiota composition may further
      result in body weight reduction by enhancing triglyceride hydrolysis and FFA
      oxidation in the adipose tissue, promoting beige adipogenesis and mitochondrial
      biogenesis, and inhibiting chronic inflammation.

PMID- 27892487
TI  - Female gender lost protective effect against disease progression in elderly
      patients with chronic hepatitis B.
AB  - Female gender and younger age are protective factors against disease progression
      in chronic hepatitis B (CHB). However, it is not clear whether the disease
      progression still remains slow in elderly females. This study investigated the
      interaction of female gender and older age on the development of cirrhosis in
      patients recorded in China Registry of Hepatitis B. A total of 17,809 CHB
      patients were enrolled in this multi-center cross-sectional study. The prevalence
      of cirrhosis in female CHB patients increased faster than that in male CHB
      patients over 50 years old. Multivariate analysis showed that the increase of
      adjusted ORs for developing cirrhosis in females started to accelerate after 50
      years old: 11.19 (95% CI: 5.93-21.11) in women versus 14.75 (95% CI: 8.35-26.07)
      in men at ages of 50-59 years, 21.67 (95% CI: 11.05-42.47) versus 24.4 (95% CI:
      13.00-45.80) at ages 60-69 years, and 18.78 (95% CI: 6.61-53.36) versus 12.09
      (95% CI: 4.35-33.61) in those over 70 years. In conclusion, the protective effect
      of female gender against cirrhosis gradually lost with increasing age, therefore
      disease progression should be monitored more closely in elderly women with CHB.

PMID- 27892488
TI  - Transition steps in peroxide reduction and a molecular switch for peroxide
      robustness of prokaryotic peroxiredoxins.
AB  - In addition to their antioxidant function, the eukaryotic peroxiredoxins (Prxs)
      facilitate peroxide-mediated signaling by undergoing controlled inactivation by
      peroxide-driven over-oxidation. In general, the bacterial enzyme lacks this
      controlled inactivation mechanism, making it more resistant to high H2O2
      concentrations. During peroxide reduction, the active site alternates between
      reduced, fully folded (FF), and oxidized, locally unfolded (LU) conformations.
      Here we present novel insights into the divergence of bacterial and human Prxs in
      robustness and sensitivity to inactivation, respectively. Structural details
      provide new insights into sub-steps during the catalysis of peroxide reduction,
      enabling the transition from an FF to a LU conformation. Complementary to
      mutational and enzymatic results, these data unravel the essential role of the C
      terminal tail of bacterial Prxs to act as a molecular switch, mediating the
      transition from an FF to a LU state. In addition, we propose that the C-terminal
      tail has influence on the propensity of the disulphide bond formation, indicating
      that as a consequence on the robustness and sensitivity to over-oxidation.
      Finally, a physical linkage between the catalytic site, the C-terminal tail and
      the oligomer interface is described.

PMID- 27892489
TI  - Laser Light Induced Transformation of Molybdenum Disulphide-Based Nanoplatelet
      Arrays.
AB  - One-pot hydrothermal synthesis of MoS2 nanoplatelet arrays on various substrates
      is perhaps the most promising approach to fabricate efficient electrocatalysts
      for hydrogen evolution reaction. However, the main challenges in this synthesis
      remain the purity and crystallinity of MoS2. In this study, we show for the first
      time that irradiation of amorphous, defect-rich MoS2 nanoplatelets with a green
      nanosecond laser at a proper irradiation dose, ca <=0.35 J cm-2, can
      significantly improve the crystallinity and purity of MoS2 nanoplatelets. The
      effect was confirmed by Raman spectroscopy investigations demonstrating a
      surprising intensity increase of the A1g and modes after the laser irradiation.
      Further increase of irradiation energy, however, resulted in the photocorrosion
      and destruction of MoS2 nanoplatelets. The variation of A1g and Raman mode
      intensities ratio depending on the green light irradiation dose was also
      presented and is discussed below.

PMID- 27892490
TI  - Identification and expression analysis of an olfactory receptor gene family in
      green plant bug Apolygus lucorum (Meyer-Dur).
AB  - Olfactory receptors are believed to play a central role in insects host-seeking,
      mating, and ovipositing. On the basis of male and female antennal transcriptome
      of adult Apolygus lucorum, a total of 110 candidate A. lucorum odorant receptors
      (AlucOR) were identified in this study including five previously annotated
      AlucORs. All the sequences were validated by cloning and sequencing. Tissue
      expression profiles analysis by RT-PCR indicated most AlucORs were antennal
      highly expressed genes. The qPCR measurements further revealed 40 AlucORs were
      significantly higher in the antennae. One AlucOR was primarily expressed in the
      female antennae, while nine AlucORs exhibited male-biased expression patterns.
      Additionally, both the RPKM value and RT-qPCR analysis showed AlucOR83 and
      AlucOR21 were much higher abundant in male antennae than in female antennae,
      suggesting their different roles in chemoreception of gender. Phylogenetic
      analysis of ORs from several Hemipteran species demonstrated that most AlucORs
      had orthologous genes, and five AlucOR-specific clades were defined. In addition,
      a sub-clade of potential male-based sex pheromone receptors were also identified
      in the phylogenetic tree of AlucORs. Our results will facilitate the functional
      studies of AlucORs, and thereby provide a foundation for novel pest management
      approaches based on these genes.

PMID- 27892492
TI  - Distribution of carbon, nitrogen and phosphorus in coastal wetland soil related
      land use in the Modern Yellow River Delta.
AB  - The delivery and distribution of nutrients in coastal wetland ecosystems is much
      related to the land use. The spatial variations of TOC, TN, NH4+-N, NO3--N and TP
      and associated soil salinity with depth in 9 kinds land uses in coastal zone of
      the modern Yellow River Delta (YRD) was evaluated based on monitoring data in
      field from 2009 to 2015. The results showed that the average contents of soil
      TOC, TN, NO3--N, NH4+-N and TP were 4.21 +/- 2.40 g kg-1, 375.91 +/- 213.44, 5.36
      +/- 9.59 and 7.20 +/- 5.58 and 591.27 +/- 91.16 mg kg-1, respectively. The high N
      and C contents were found in cropland in southern part and low values in natural
      wetland, while TP was relatively stable both in profiles and in different land
      uses. The land use, land formation age and salinity were important factors
      influencing distributions of TOC and N. Higher contents of TOC and N were
      observed in older formation age lands in whole study region, while the opposite
      regulation were found in new-born natural wetland, indicating that the
      anthropogenic activities could greatly alter the original distribution
      regulations of nutrients in coastal natural wetlands by changing the regional
      land use.

PMID- 27892491
TI  - Selected Biomarkers Revealed Potential Skin Toxicity Caused by Certain Copper
      Compounds.
AB  - Copper is an essential mineral and plays important roles in skin growth and
      activity. Copper delivery through skin can provide beneficial effects but its
      potential to induce skin irritation reactions is often overlooked. Data on dermal
      toxicity caused by copper compounds is scant. Some recognized in vitro skin
      toxicity methods are unsuitable for all metal compounds. Here, we employ a
      keratinocyte-based model and evaluated the skin irritation potential of copper
      compounds at cellular, genomic and proteomic levels. We determined cell viability
      and cytotoxicity by using tetrazolium reduction assay and Lactate Dehydrogenase
      (LDH) assay, performed real-time PCR and protein quantification to assess the
      expression of biomarkers after treating cells with copper peptide (GHK-Cu),
      copper chloride (CuCl2) and copper acetate (Cu(OAc)2). These copper compounds
      exhibited different irritancy potentials at the same treatment concentrations.
      GHK-Cu was not cytotoxic and did not induce any significant change in the
      expression levels of various skin irritation-related biomarkers. IL-1alpha and IL
      8, HSPA1A and FOSL1 were significantly upregulated following 24-h treatment with
      CuCl2 and Cu(OAc)2 at 58 and 580 MUM without concomitant inhibition in cell
      viability. GHK-Cu has a low potential of inducing skin irritation and therefore
      provides a safer alternative for the delivery of copper through skin.

PMID- 27892493
TI  - Autologous temporomandibular joint reconstruction independent of exogenous
      additives: a proof-of-concept study for guided self-generation.
AB  - Joint defects are complex and difficult to reconstruct. By exploiting the body's
      own regenerative capacity, we aimed to individually generate anatomically precise
      neo-tissue constructs for autologous joint reconstruction without using any
      exogenous additives. In a goat model, CT scans of the mandibular condyle
      including articular surface and a large portion of the ascending ramus were
      processed using computer-aided design and manufacturing. A corresponding
      hydroxylapatite negative mold was printed in 3D and temporarily embedded into the
      transition zone of costal periosteum and perichondrium. A demineralized bone
      matrix scaffold implanted on the contralateral side served as control. Neo-tissue
      constructs obtained by guided self-generation exhibited accurate configuration,
      robust vascularization, biomechanical stability, and function. After autologous
      replacement surgery, the constructs showed stable results with similar
      anatomical, histological, and functional findings compared to native controls.
      Further studies are required to assess long-term outcome and possible extensions
      to other further applications. The absence of exogenous cells, growth factors,
      and scaffolds may facilitate clinical translation of this approach.

PMID- 27892495
TI  - Quorum Regulated Resistance of Vibrio cholerae against Environmental
      Bacteriophages.
AB  - Predation by bacteriophages can significantly influence the population structure
      of bacterial communities. Vibrio cholerae the causative agent of cholera
      epidemics interacts with numerous phages in the aquatic ecosystem, and in the
      intestine of cholera patients. Seasonal epidemics of cholera reportedly collapse
      due to predation of the pathogen by phages. However, it is not clear how
      sufficient number of the bacteria survive to seed the environment in the
      subsequent epidemic season. We found that bacterial cell density-dependent gene
      expression termed "quorum sensing" which is regulated by signal molecules called
      autoinducers (AIs) can protect V. cholerae against predatory phages. V. cholerae
      mutant strains carrying inactivated AI synthase genes were significantly more
      susceptible to multiple phages compared to the parent bacteria. Likewise when
      mixed cultures of phage and bacteria were supplemented with exogenous
      autoinducers CAI-1 or AI-2 produced by recombinant strains carrying cloned AI
      synthase genes, increased survival of V. cholerae and a decrease in phage titer
      was observed. Mutational analyses suggested that the observed effects of
      autoinducers are mediated in part through the quorum sensing-dependent production
      of haemaglutinin protease, and partly through downregulation of phage receptors.
      These results have implication in developing strategies for phage mediated
      control of cholera.

PMID- 27892494
TI  - Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be
      transferred to exosomes.
AB  - Recent studies have shown that circular RNAs (circRNAs) are abundant, widely
      expressed in mammals, and can display cell-type specific expression. However, how
      production of circRNAs is regulated and their precise biological function remains
      largely unknown. To study how circRNAs might be regulated during colorectal
      cancer progression, we used three isogenic colon cancer cell lines that differ
      only in KRAS mutation status. Cellular RNAs from the parental DLD-1 cells that
      contain both wild-type and G13D mutant KRAS alleles and isogenically-matched
      derivative cell lines, DKO-1 (mutant KRAS allele only) and DKs-8 (wild-type KRAS
      allele only) were analyzed using RNA-Seq. We developed a bioinformatics pipeline
      to identify and evaluate circRNA candidates from RNA-Seq data. Hundreds of high
      quality circRNA candidates were identified in each cell line. Remarkably,
      circRNAs were significantly down-regulated at a global level in DLD-1 and DKO-1
      cells compared to DKs-8 cells, indicating a widespread effect of mutant KRAS on
      circRNA abundance. This finding was confirmed in two independent colon cancer
      cell lines HCT116 (KRAS mutant) and HKe3 (KRAS WT). In all three cell lines,
      circRNAs were also found in secreted extracellular-vesicles, and circRNAs were
      more abundant in exosomes than cells. Our results suggest that circRNAs may serve
      as promising cancer biomarkers.

PMID- 27892496
TI  - EWAS: epigenome-wide association studies software 1.0 - identifying the
      association between combinations of methylation levels and diseases.
AB  - Similar to the SNP (single nucleotide polymorphism) data, there is non-random
      association of the DNA methylation level (we call it methylation disequilibrium,
      MD) between neighboring methylation loci. For the case-control study of complex
      diseases, it is important to identify the association between methylation levels
      combination types (we call it methylecomtype) and diseases/phenotypes. We
      extended the classical framework of SNP haplotype-based association study in
      population genetics to DNA methylation level data, and developed a software EWAS
      to identify the disease-related methylecomtypes. EWAS can provide the following
      basic functions: (1) calculating the DNA methylation disequilibrium coefficient
      between two CpG loci; (2) identifying the MD blocks across the whole genome; (3)
      carrying out case-control association study of methylecomtypes and identifying
      the disease-related methylecomtypes. For a DNA methylation level data set
      including 689 samples (354 cases and 335 controls) and 473864 CpG loci, it takes
      only about 25 min to complete the full scan. EWAS v1.0 can rapidly identify the
      association between combinations of methylation levels (methylecomtypes) and
      diseases. EWAS v1.0 is freely available at: http://www.ewas.org.cn or
      http://www.bioapp.org/ewas.

PMID- 27892497
TI  - Optimising Antibiotic Usage to Treat Bacterial Infections.
AB  - The increase in antibiotic resistant bacteria poses a threat to the continued use
      of antibiotics to treat bacterial infections. The overuse and misuse of
      antibiotics has been identified as a significant driver in the emergence of
      resistance. Finding optimal treatment regimens is therefore critical in ensuring
      the prolonged effectiveness of these antibiotics. This study uses mathematical
      modelling to analyse the effect traditional treatment regimens have on the
      dynamics of a bacterial infection. Using a novel approach, a genetic algorithm,
      the study then identifies improved treatment regimens. Using a single antibiotic
      the genetic algorithm identifies regimens which minimise the amount of antibiotic
      used while maximising bacterial eradication. Although exact treatments are highly
      dependent on parameter values and initial bacterial load, a significant common
      trend is identified throughout the results. A treatment regimen consisting of a
      high initial dose followed by an extended tapering of doses is found to optimise
      the use of antibiotics. This consistently improves the success of eradicating
      infections, uses less antibiotic than traditional regimens and reduces the time
      to eradication. The use of genetic algorithms to optimise treatment regimens
      enables an extensive search of possible regimens, with previous regimens
      directing the search into regions of better performance.

PMID- 27892498
TI  - Sensitization with vaccinia virus encoding H5N1 hemagglutinin restores immune
      potential against H5N1 influenza virus.
AB  - H5N1 highly pathogenic avian influenza (H5N1 HPAI) virus causes elevated
      mortality compared with seasonal influenza viruses like H1N1 pandemic influenza
      (H1N1 pdm) virus. We identified a mechanism associated with the severe symptoms
      seen with H5N1 HPAI virus infection. H5N1 HPAI virus infection induced a decrease
      of dendritic cell number in the splenic extrafollicular T-cell zone and impaired
      formation of the outer layers of B-cell follicles, resulting in insufficient
      levels of antibody production after infection. However, in animals vaccinated
      with a live recombinant vaccinia virus expressing the H5 hemagglutinin, infection
      with H5N1 HPAI virus induced parafollicular dendritic cell accumulation and
      efficient antibody production. These results indicate that a recombinant vaccinia
      encoding H5 hemagglutinin gene does not impair dendritic cell recruitment and can
      be a useful vaccine candidate.

PMID- 27892499
TI  - Recognition of extremophilic archaeal viruses by eukaryotic cells: a promising
      nanoplatform from the third domain of life.
AB  - Viruses from the third domain of life, Archaea, exhibit unusual features
      including extreme stability that allow their survival in harsh environments. In
      addition, these species have never been reported to integrate into human or any
      other eukaryotic genomes, and could thus serve for exploration of novel medical
      nanoplatforms. Here, we selected two archaeal viruses Sulfolobus monocaudavirus 1
      (SMV1) and Sulfolobus spindle shaped virus 2 (SSV2) owing to their unique spindle
      shape, hyperthermostable and acid-resistant nature and studied their interaction
      with mammalian cells. Accordingly, we followed viral uptake, intracellular
      trafficking and cell viability in human endothelial cells of brain (hCMEC/D3
      cells) and umbilical vein (HUVEC) origin. Whereas SMV1 is efficiently
      internalized into both types of human cells, SSV2 differentiates between HUVECs
      and hCMEC/D3 cells, thus opening a path for selective cell targeting. On
      internalization, both viruses localize to the lysosomal compartments. Neither
      SMV1, nor SSV2 induced any detrimental effect on cell morphology, plasma membrane
      and mitochondrial functionality. This is the first study demonstrating
      recognition of archaeal viruses by eukaryotic cells which provides good basis for
      future exploration of archaeal viruses in bioengineering and development of
      multifunctional vectors.

PMID- 27892501
TI  - A social contagious model of the obesity epidemic.
AB  - Obesity has been recognized as a global epidemic by WHO, followed by many
      empirical evidences to prove its infectiousness. However, the inter-person
      spreading dynamics of obesity are seldom studied. A distinguishing feature of the
      obesity epidemic is that it is driven by a social contagion process which cannot
      be perfectly described by the infectious disease models. In this paper, we
      propose a novel belief decision model based on the famous Dempster-Shafer theory
      of evidence to model obesity epidemic as the competing spread of two obesity
      related behaviors: physical inactivity and physical activity. The transition of
      health states is described by an SIS model. Results reveal the existence of
      obesity epidemic threshold, above which obesity is quickly eradicated. When
      increasing the fading level of information spread, enlarging the clustering of
      initial obese seeds, or introducing small-world characteristics into the network
      topology, the threshold is easily met. Social discrimination against the obese
      people plays completely different roles in two cases: on one hand, when obesity
      cannot be eradicated, social discrimination can reduce the number of obese
      people; on the other hand, when obesity is eradicable, social discrimination may
      instead cause it breaking out.

PMID- 27892500
TI  - Four translation initiation pathways employed by the leaderless mRNA in
      eukaryotes.
AB  - mRNAs lacking 5' untranslated regions (leaderless mRNAs) are molecular relics of
      an ancient translation initiation pathway. Nevertheless, they still represent a
      significant portion of transcriptome in some taxons, including a number of
      eukaryotic species. In bacteria and archaea, the leaderless mRNAs can bind non
      dissociated 70 S ribosomes and initiate translation without protein initiation
      factors involved. Here we use the Fleeting mRNA Transfection technique (FLERT) to
      show that translation of a leaderless reporter mRNA is resistant to conditions
      when eIF2 and eIF4F, two key eukaryotic translation initiation factors, are
      inactivated in mammalian cells. We report an unconventional translation
      initiation pathway utilized by the leaderless mRNA in vitro, in addition to the
      previously described 80S-, eIF2-, or eIF2D-mediated modes. This mechanism is a
      bacterial-like eIF5B/IF2-assisted initiation that has only been reported for
      hepatitis C virus-like internal ribosome entry sites (IRESs). Therefore, the
      leaderless mRNA is able to take any of four different translation initiation
      pathways in eukaryotes.

PMID- 27892502
TI  - Mitochondrial fat oxidation is essential for lipid-induced inflammation in
      skeletal muscle in mice.
AB  - Inflammation, lipotoxicity and mitochondrial dysfunction have been implicated in
      the pathogenesis of obesity-induced insulin resistance and type 2 diabetes.
      However, how these factors are intertwined in the development of obesity/insulin
      resistance remains unclear. Here, we examine the role of mitochondrial fat
      oxidation on lipid-induced inflammation in skeletal muscle. We used skeletal
      muscle-specific Cpt1b knockout mouse model where the inhibition of mitochondrial
      fatty acid oxidation results in accumulation of lipid metabolites in muscle and
      elevated circulating free fatty acids. Gene expression of pro-inflammatory
      cytokines, chemokines, and cytokine- and members of TLR-signalling pathways were
      decreased in Cpt1bm-/- muscle. Inflammatory signalling pathways were not
      activated when evaluated by multiplex and immunoblot analysis. In addition, the
      inflammatory response to fatty acids was reduced in primary muscle cells derived
      from Cpt1bm-/- mice. Gene expression of Cd11c, the M1 macrophage marker, was
      decreased; while Cd206, the M2 macrophage marker, was increased in skeletal
      muscle of Cpt1bm-/- mice. Finally, expression of pro-inflammatory markers was
      decreased in white adipose tissue of Cpt1bm-/- mice. We show that the
      inflammatory response elicited by elevated intracellular lipids in skeletal
      muscle is repressed in Cpt1bm-/- mice, strongly supporting the hypothesis that
      mitochondrial processing of fatty acids is essential for the lipid-induction of
      inflammation in muscle.

PMID- 27892503
TI  - Trans-translation is essential in the human pathogen Legionella pneumophila.
AB  - Trans-translation is a ubiquitous bacterial mechanism for ribosome rescue in the
      event of translation stalling. Although trans-translation is not essential in
      several bacterial species, it has been found essential for viability or virulence
      in a wide range of pathogens. We describe here that trans-translation is
      essential in the human pathogen Legionella pneumophila, the etiologic agent of
      Legionnaire's disease (LD), a severe form of nosocomial and community-acquired
      pneumonia. The ssrA gene coding for tmRNA, the key component of trans
      translation, could not be deleted in L. pneumophila. To circumvent this and
      analyse the consequences of impaired trans-translation, we placed ssrA under the
      control of a chemical inducer. Phenotypes associated with the inhibition of ssrA
      expression include growth arrest in rich medium, hampered cell division, and
      hindered ability to infect eukaryotic cells (amoebae and human macrophages). LD
      is often associated with failure of antibiotic treatment and death (>10% of
      clinical cases). Decreasing tmRNA levels led to significantly higher sensitivity
      to ribosome-targeting antibiotics, including to erythromycin. We also detected a
      higher sensitivity to the transcription inhibitor rifampicin. Both antibiotics
      are recommended treatments for LD. Thus, interfering with trans-translation may
      not only halt the infection, but could also potentiate the recommended
      therapeutic treatments of LD.

PMID- 27892505
TI  - In vivo measurement of hemodynamic information in stenosed rat blood vessels
      using X-ray PIV.
AB  - Measurements of the hemodynamic information of blood flows, especially wall shear
      stress (WSS), in animal models with circulatory vascular diseases (CVDs) are
      important to understand the pathological mechanism of CVDs. In this study, X-ray
      particle image velocimetry (PIV) with high spatial resolution was applied to
      obtain velocity field information in stenosed blood vessels with high WSS. 3D
      clips fabricated with a 3D printer were applied to the abdominal aorta of a rat
      cadaver to induce artificial stenosis in the real blood vessel of an animal
      model. The velocity and WSS information of blood flows in the stenosed vessel
      were obtained and compared at various stenosis severities. In vivo measurement
      was also conducted by fastening a stenotic clip on a live rat model through
      surgical intervention to reduce the flow rate to match the limited temporal
      resolution of the present X-ray PIV system. Further improvement of the temporal
      resolution of the system might be able to provide in vivo measurements of
      hemodynamic information from animal disease models under physiological
      conditions. The present results would be helpful for understanding the relation
      between hemodynamic characteristics and the pathological mechanism in animal CVD
      models.

PMID- 27892504
TI  - Soluble Siglec-5 associates to PSGL-1 and displays anti-inflammatory activity.
AB  - Interactions between endothelial selectins and the leukocyte counter-receptor
      PSGL1 mediates leukocyte recruitment to inflammation sites. PSGL1 is highly
      sialylated, making it a potential ligand for Siglec-5, a leukocyte-receptor that
      recognizes sialic acid structures. Binding assays using soluble Siglec-5 variants
      (sSiglec-5/C4BP and sSiglec-5/Fc) revealed a dose- and calcium-dependent binding
      to PSGL1. Pre-treatment of PSGL1 with sialidase reduced Siglec-5 binding by 79 +/
      4%. In confocal immune-fluorescence assays, we observed that 50% of Peripheral
      Blood Mononuclear Cells (PBMCs) simultaneously express PSGL1 and Siglec-5.
      Duolink-proximity ligation analysis demonstrated that PSGL1 and Siglec-5 are in
      close proximity (<40 nm) in 31 +/- 4% of PBMCs. In vitro perfusion assays
      revealed that leukocyte-rolling over E- and P-selectin was inhibited by sSiglec
      5/Fc or sSiglec-5/C4BP, while adhesion onto VCAM1 was unaffected. When applied to
      healthy mice (0.8 mg/kg), sSiglec-5/C4BP significantly reduced the number of
      rolling leukocytes under basal conditions (10.9 +/- 3.7 versus 23.5 +/- 9.3
      leukocytes/field/min for sSiglec-5/C4BP-treated and control mice, respectively; p
      = 0.0093). Moreover, leukocyte recruitment was inhibited over a 5-h observation
      period in an in vivo model of TNFalpha-induced inflammation following injection
      sSiglec-5/C4BP (0.8 mg/kg). Our data identify PSGL1 as a ligand for Siglec-5, and
      soluble Siglec-5 variants appear efficient in blocking PSGL1-mediated leukocyte
      rolling and the inflammatory response in general.

PMID- 27892506
TI  - Negative feedback regulation of ABA biosynthesis in peanut (Arachis hypogaea): a
      transcription factor complex inhibits AhNCED1 expression during water stress.
AB  - Abscisic acid (ABA), a key plant stress-signaling hormone, is produced in
      response to drought and counteracts the effects of this stress. The accumulation
      of ABA is controlled by the enzyme 9-cis-epoxycarotenoid dioxygenase (NCED). In
      Arabidopsis, NCED3 is regulated by a positive feedback mechanism by ABA. In this
      study in peanut (Arachis hypogaea), we demonstrate that ABA biosynthesis is also
      controlled by negative feedback regulation, mediated by the inhibitory effect on
      AhNCED1 transcription of a protein complex between transcription factors AhNAC2
      and AhAREB1. AhNCED1 was significantly down-regulated after PEG treatment for 10
      h, at which time ABA content reached a peak. A ChIP-qPCR assay confirmed AhAREB1
      and AhNAC2 binding to the AhNCED1 promoter in response to ABA. Moreover, the
      interaction between AhAREB1 and AhNAC2, and a transient expression assay showed
      that the protein complex could negatively regulate the expression of AhNCED1. The
      results also demonstrated that AhAREB1 was the key factor in AhNCED1 feedback
      regulation, while AhNAC2 played a subsidiary role. ABA reduced the rate of
      AhAREB1 degradation and enhanced both the synthesis and degradation rate of the
      AhNAC2 protein. In summary, the AhAREB1/AhNAC2 protein complex functions as a
      negative feedback regulator of drought-induced ABA biosynthesis in peanut.

PMID- 27892507
TI  - Variations in abundance, diversity and community composition of airborne fungi in
      swine houses across seasons.
AB  - We examined the abundance, diversity and community composition of airborne fungi
      in swine houses during winter and summer seasons by using quantitative PCR and
      Illumina HiSeq sequencing of ITS1 region. The abundance of airborne fungi varied
      significantly only between seasons, while fungal diversity varied significantly
      both within and between seasons, with both abundance and diversity peaked in
      winter. The fungal OTU composition was largely structured by the swine house unit
      and season as well as by their interactions. Of the measured microclimate
      variables, relative humidity, particulate matters (PMs), ammonia, and stocking
      density were significantly correlated with fungal OTU composition. The variation
      in beta diversity was higher within swine houses during summer, which indicates
      that the airborne fungal community composition was more heterogeneous in summer
      compared to winter. We also identified several potential allergen/pathogen
      related fungal genera in swine houses. The total relative abundance of potential
      allergen/pathogen related fungal genera varied between swine houses in both
      seasons, and showed positive correlation with PM2.5. Overall, our findings show
      that the abundance, diversity and composition of airborne fungi are highly
      variable in swine houses and to a large extent structured by indoor microclimate
      variables of swine houses.

PMID- 27892508
TI  - Levy random walks on multiplex networks.
AB  - Random walks constitute a fundamental mechanism for many dynamics taking place on
      complex networks. Besides, as a more realistic description of our society,
      multiplex networks have been receiving a growing interest, as well as the
      dynamical processes that occur on top of them. Here, inspired by one specific
      model of random walks that seems to be ubiquitous across many scientific fields,
      the Levy flight, we study a new navigation strategy on top of multiplex networks.
      Capitalizing on spectral graph and stochastic matrix theories, we derive
      analytical expressions for the mean first passage time and the average time to
      reach a node on these networks. Moreover, we also explore the efficiency of Levy
      random walks, which we found to be very different as compared to the single layer
      scenario, accounting for the structure and dynamics inherent to the multiplex
      network. Finally, by comparing with some other important random walk processes
      defined on multiplex networks, we find that in some region of the parameters, a
      Levy random walk is the most efficient strategy. Our results give us a deeper
      understanding of Levy random walks and show the importance of considering the
      topological structure of multiplex networks when trying to find efficient
      navigation strategies.

PMID- 27892509
TI  - Evolution of cooperation under indirect reciprocity and arbitrary exploration
      rates.
AB  - Cooperation has been recognized as an evolutionary puzzle since Darwin, and
      remains identified as one of the biggest challenges of the XXIst century.
      Indirect Reciprocity (IR), a key mechanism that humans employ to cooperate with
      each other, establishes that individual behaviour depends on reputations, which
      in turn evolve depending on social norms that classify behaviours as good or bad.
      While it is well known that different social norms give rise to distinct
      cooperation levels, it remains unclear how the performance of each norm is
      influenced by the random exploration of new behaviours, often a key component of
      social dynamics where a plethora of stimuli may compel individuals to deviate
      from pre-defined behaviours. Here we study, for the first time, the impact of
      varying degrees of exploration rates - the likelihood of spontaneously adopting
      another strategy, akin to a mutation probability in evolutionary dynamics - in
      the emergence of cooperation under IR. We show that high exploration rates may
      either improve or harm cooperation, depending on the underlying social norm at
      work. Regarding some of the most popular social norms studied to date, we find
      that cooperation under Simple-standing and Image-score is enhanced by high
      exploration rates, whereas the opposite occurs for Stern-judging and Shunning.

PMID- 27892510
TI  - Strong quantum scarring by local impurities.
AB  - We discover and characterise strong quantum scars, or quantum eigenstates
      resembling classical periodic orbits, in two-dimensional quantum wells perturbed
      by local impurities. These scars are not explained by ordinary scar theory, which
      would require the existence of short, moderately unstable periodic orbits in the
      perturbed system. Instead, they are supported by classical resonances in the
      unperturbed system and the resulting quantum near-degeneracy. Even in the case of
      a large number of randomly scattered impurities, the scars prefer distinct
      orientations that extremise the overlap with the impurities. We demonstrate that
      these preferred orientations can be used for highly efficient transport of
      quantum wave packets across the perturbed potential landscape. Assisted by the
      scars, wave-packet recurrences are significantly stronger than in the unperturbed
      system. Together with the controllability of the preferred orientations, this
      property may be very useful for quantum transport applications.

PMID- 27892511
TI  - The clinicopathological and prognostic significance of PD-L1 expression in
      gastric cancer: a meta-analysis of 10 studies with 1,901 patients.
AB  - The prognostic value of programmed death-ligand 1 (PD-L1) in gastric cancer (GC)
      remains controversial. To clarify this problem, we performed a meta-analysis of
      research studies identified in the PubMed, EMBASE and the Cochrane Library
      databases. A total of 1,901 patients in 10 studies were enrolled in this meta
      analysis, and the pooled hazard ratio (HR) of 1.64 (95% CI 1.11 to 2.43; P =
      0.01) indicated that PD-L1 expression is associated with a shorter overall
      survival (OS). The pooled odds ratios (ORs) indicated that PD-L1 expression was
      associated with tumour size (OR = 1.87, 95% CI 1.25 to 2.78; P = 0.002) and lymph
      node status (OR = 2.17, 95% CI 1.04 to 4.52; P = 0.04). However, PD-L1 had no
      correlation with gender, age, cancer location, differentiation, depth of
      invasion, and tumour stage. This meta-analysis indicates that PD-L1 expression is
      a valuable predictor of the prognosis of patients with GC. PD-L1 expression could
      be used for identifying a subgroup of patients, who would potentially benefit
      from targeted therapy against PD-1 or PD-L1. Well-designed large-cohort studies
      are needed to confirm these findings.

PMID- 27892512
TI  - Where is iron in erionite? A multidisciplinary study on fibrous erionite-Na from
      Jersey (Nevada, USA).
AB  - Fibrous erionite is a mineral fibre of great concern but to date mechanisms by
      which it induces cyto- and geno-toxic damage, and especially the role of iron
      associated to this zeolite species, remain poorly understood. One of the reasons
      is that we still don't know exactly where iron is in natural erionite. This work
      is focused on fibrous erionite-Na from Jersey (Nevada, USA) and attempts to draw
      a general model of occurrence of iron in erionite and relationship with toxicity
      mechanisms. It was found that iron is present as 6-fold coordinated Fe3+ not part
      of the zeolite structure. The heterogeneous nature of the sample was revealed as
      receptacle of different iron-bearing impurities (amorphous iron-rich
      nanoparticles, micro-particles of iron oxides/hydroxides, and flakes of
      nontronite). If iron is not part of the structure, its role should be considered
      irrelevant for erionite toxicity, and other factors like biopersistence should be
      invoked. An alternative perspective to the proposed model is that iron rich nano
      particles and nontronite dissolve in the intracellular acidic environment,
      leaving a residue of iron atoms at specific surface sites anchored to the windows
      of the zeolite channels. These sites may be active later as low nuclearity
      groups.

PMID- 27892513
TI  - Dissociable early attentional control mechanisms underlying cognitive and
      affective conflicts.
AB  - It has been well documented that cognitive conflict is sensitive to the relative
      proportion of congruent and incongruent trials. However, few studies have
      examined whether affective conflict processing is modulated as a function of
      proportion congruency (PC). To address this question we recorded event-related
      potentials (ERP) while subjects performed both cognitive and affective face-word
      Stroop tasks. By varying the proportion of congruent and incongruent trials in
      each block, we examined the extent to which PC impacts both cognitive and
      affective conflict control at different temporal stages. Results showed that in
      the cognitive task an anteriorly localized early N2 component occurred
      predominantly in the low proportion congruency context, whereas in the affective
      task it was found to occur in the high proportion congruency one. The N2 effects
      across the two tasks were localized to the dorsolateral prefrontal cortex, where
      responses were increased in the cognitive task but decreased in the affective
      one. Furthermore, high proportions of congruent items produced both larger
      amplitude of a posteriorly localized sustained potential component and a larger
      behavioral Stroop effect in cognitive and affective tasks. Our findings suggest
      that cognitive and affective conflicts engage early dissociable attentional
      control mechanisms and a later common conflict response system.

PMID- 27892514
TI  - GWAS study using DNA pooling strategy identifies association of variant rs4910623
      in OR52B4 gene with anti-VEGF treatment response in age-related macular
      degeneration.
AB  - Pooled DNA based GWAS to determine genetic association of SNPs with visual acuity
      (VA) outcome in anti-vascular endothelial growth factor (anti-VEGF) treated
      neovascular age-related macular degeneration (nAMD) patients. We performed pooled
      DNA based GWAS on 285 anti-VEGF treated nAMD patients using high density Illumina
      4.3 M array. Primary outcome was change in VA in Early Treatment Diabetic
      Retinopathy Study (ETDRS) letters after 6 months of anti-VEGF treatment (patients
      who lost >=5 ETDRS letters classified as non-responders and all remaining
      classified as responders). GWAS analysis identified 44 SNPs of interest: 37 with
      strong evidence of association (p < 9 * 10-8), 2 in drug resistance genes (p < 5
      * 10-6) and 5 nonsynonymous changes (p < 1 * 10-4). In the validation phase,
      individual genotyping of 44 variants showed three SNPs (rs4910623 p = 5.6 * 10-5,
      rs323085 p = 6.5 * 10-4 and rs10198937 p = 1.30 * 10-3) remained associated with
      VA response at 6 months. SNP rs4910623 also associated with treatment response at
      3 months (p = 1.5 * 10-3). Replication of these three SNPs in 376 patients
      revealed association of rs4910623 with poor VA response after 3 and 6 months of
      treatment (p = 2.4 * 10-3 and p = 3.5 * 10-2, respectively). Meta-analysis of
      both cohorts (673 samples) confirmed association of rs4910623 with poor VA
      response after 3 months (p = 1.2 * 10-5) and 6 months (p = 9.3 * 10-6) of
      treatment in nAMD patients.

PMID- 27892515
TI  - Heteronanostructured Co@carbon nanotubes-graphene ternary hybrids: synthesis,
      electromagnetic and excellent microwave absorption properties.
AB  - In order to explore high efficiency microwave absorption materials,
      heteronanostructured Co@carbon nanotubes-graphene (Co@CNTs-G) ternary hybrids
      were designed and produced through catalytic decomposition of acetylene at the
      designed temperature (400, 450, 500 and 550  degrees C) over Co3O4/reduced
      graphene oxide (Co3O4/RGO). By regulating the reaction temperatures, different
      CNT contents of Co@CNTs-G ternary hybrids could be synthesized. The
      investigations indicated that the as-prepared heteronanostructured Co@CNTs-G
      ternary hybrids exhibited excellent microwave absorption properties, and their
      electromagnetic and microwave absorption properties could be tuned by the CNT
      content. The minimum reflection loss (RL) value reached approximately -65.6, 
      58.1, -41.1 and -47.5 dB for the ternary hybrids synthesized at 400, 450, 500 and
      550  degrees C, respectively. And RL values below -20 dB (99% of electromagnetic
      wave attenuation) could be obtained over the as-prepared Co@CNTs-G ternary
      hybrids in the large frequency range. Moreover, based on the obtained results,
      the possible enhanced microwave absorption mechanisms were discussed in details.
      Therefore, a simple approach was proposed to explore the high performance
      microwave absorbing materials as well as to expand the application field of
      graphene-based materials.

PMID- 27892516
TI  - In vivo coherent Raman imaging of the melanomagenesis-associated pigment
      pheomelanin.
AB  - Melanoma is the most deadly form of skin cancer with a yearly global incidence
      over 232,000 patients. Individuals with fair skin and red hair exhibit the
      highest risk for developing melanoma, with evidence suggesting the red/blond
      pigment known as pheomelanin may elevate melanoma risk through both UV radiation
      dependent and -independent mechanisms. Although the ability to identify,
      characterize, and monitor pheomelanin within skin is vital for improving our
      understanding of the underlying biology of these lesions, no tools exist for real
      time, in vivo detection of the pigment. Here we show that the distribution of
      pheomelanin in cells and tissues can be visually characterized non-destructively
      and noninvasively in vivo with coherent anti-Stokes Raman scattering (CARS)
      microscopy, a label-free vibrational imaging technique. We validated our CARS
      imaging strategy in vitro to in vivo with synthetic pheomelanin, isolated
      melanocytes, and the Mc1re/e, red-haired mouse model. Nests of pheomelanotic
      melanocytes were observed in the red-haired animals, but not in the genetically
      matched Mc1re/e; Tyrc/c ("albino-red-haired") mice. Importantly, samples from
      human amelanotic melanomas subjected to CARS imaging exhibited strong
      pheomelanotic signals. This is the first time, to our knowledge, that pheomelanin
      has been visualized and spatially localized in melanocytes, skin, and human
      amelanotic melanomas.

PMID- 27892517
TI  - Chorioamnionitis appears not to be a Risk Factor for Patent Ductus Arteriosus in
      Preterm Infants: A Systematic Review and Meta-Analysis.
AB  - The contribution of chorioamnionitis (CA) to mortality and morbidity in preterm
      infants is difficult to assess because observational studies frequently present
      significant differences in baseline characteristics of the infants exposed or non
      exposed to CA. In an attempt to perform a thorough assessment of the possible
      association between CA and patent ductus arteriosus (PDA) in preterm infants, we
      conducted a meta-analysis in which adjusted odds ratios (ORs) were pooled and we
      analyzed the effects of potential confounders, such as gestational age (GA) or
      birth weight (BW). We identified 45 relevant studies (27186 patients, 7742 CA
      cases). Random effects meta-analysis of crude ORs showed a significant positive
      association between CA and PDA (OR 1.352, 95% CI 1.172 to 1.560). Adjusted ORs
      were reported in 11 studies (19577 infants). Meta-analysis of these studies
      showed a significant negative association between CA and PDA (OR 0.802, 95% CI
      0.751 to 0.959). Meta-regression showed that the differences in GA or BW between
      the CA-exposed and non-exposed groups were significantly correlated with the
      effect size of the association between PDA and CA. In conclusion, our study
      confirms that confounders need to be taken into account when assessing the
      association between CA and clinical outcomes in preterm infants.

PMID- 27892519
TI  - Current induced polycrystalline-to-crystalline transformation in vanadium dioxide
      nanowires.
AB  - Vanadium dioxide (VO2) exhibits a reversible insulator-metal phase transition
      that is of significant interest in energy-efficient nanoelectronic and
      nanophotonic devices. In these applications, crystalline materials are usually
      preferred for their superior electrical transport characteristics as well as
      spatial homogeneity and low surface roughness over the device area for reduced
      scattering. Here, we show applied electrical currents can induce a permanent
      reconfiguration of polycrystalline VO2 nanowires into crystalline nanowires,
      resulting in a dramatically reduced hysteresis across the phase transition and
      reduced resistivity. Low currents below 3 mA were sufficient to cause the local
      temperature in the VO2 to reach about 1780 K to activate the irreversible
      polycrystalline-to-crystalline transformation. The crystallinity was confirmed by
      electron microscopy and diffraction analyses. This simple yet localized post
      processing of insulator-metal phase transition materials may enable new methods
      of studying and fabricating nanoscale structures and devices formed from these
      materials.

PMID- 27892518
TI  - Brain microbiota disruption within inflammatory demyelinating lesions in multiple
      sclerosis.
AB  - Microbial communities reside in healthy tissues but are often disrupted during
      disease. Bacterial genomes and proteins are detected in brains from humans,
      nonhuman primates, rodents and other species in the absence of neurological
      disease. We investigated the composition and abundance of microbiota in frozen
      and fixed autopsied brain samples from patients with multiple sclerosis (MS) and
      age- and sex-matched nonMS patients as controls, using neuropathological,
      molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria
      to be the dominant phylum with restricted diversity in cerebral white matter (WM)
      from MS compared to nonMS patients. Both clinical groups displayed 1,200-1,400
      bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses
      showed a predominance of Proteobacteria in progressive MS patients' WM,
      associated with increased inflammatory gene expression, relative to a broader
      range of bacterial phyla in relapsing-remitting MS patients' WM. Although
      bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities
      were observed in all patients, PGN immunodetection was correlated with
      demyelination and neuroinflammation in MS brains. Principal component analysis
      revealed that demyelination, PGN and inflammatory gene expression accounted for
      86% of the observed variance. Thus, inflammatory demyelination is linked to an
      organ-specific dysbiosis in MS that could contribute to underlying disease
      mechanisms.

PMID- 27892520
TI  - Internal epitope tagging informed by relative lack of sequence conservation.
AB  - Many experimental techniques rely on specific recognition and stringent binding
      of proteins by antibodies. This can readily be achieved by introducing an epitope
      tag. We employed an approach that uses a relative lack of evolutionary
      conservation to inform epitope tag site selection, followed by integration of the
      tag-coding sequence into the endogenous locus in zebrafish. We demonstrate that
      an internal epitope tag is accessible for antibody binding, and that tagged
      proteins retain wild type function.

PMID- 27892521
TI  - A novel bio-engineering approach to generate an eminent surface-functionalized
      template for selective detection of female sex pheromone of Helicoverpa armigera.
AB  - Plant pests exert serious effects on food production due to which the global crop
      yields are reduced by ~20-40 percent per year. Hence to meet the world's food
      needs, loses of food due to crop pests must be reduced. Herein the silicon
      dioxide based MEMS devices are covalently functionalized for robust and efficient
      optical sensing of the female sex pheromones of the pests like Helicoverpa
      armigera for the first time in literature. The functionalized devices are also
      capable of selectively measuring the concentration of this pheromone at femtogram
      level which is much below the concentration of pheromone at the time of pest
      infestation in an agricultural field. Experiments are also performed in a
      confined region in the presence of male and female pests and tomato plants which
      directly mimics the real environmental conditions. Again the reversible use and
      absolutely trouble free transportation of these pheromone nanosensors heightens
      their potentials for commercial use. Overall, a novel and unique approach for the
      selective and reversible sensing of female sex pheromones of certain hazardous
      pests is reported herein which may be efficiently and economically carried
      forward from the research laboratory to the agricultural field.

PMID- 27892524
TI  - Vectorized magnetometer for space applications using electrical readout of atomic
      scale defects in silicon carbide.
AB  - Magnetometers are essential for scientific investigation of planetary bodies and
      are therefore ubiquitous on missions in space. Fluxgate and optically pumped
      atomic gas based magnetometers are typically flown because of their proven
      performance, reliability, and ability to adhere to the strict requirements
      associated with space missions. However, their complexity, size, and cost prevent
      their applicability in smaller missions involving cubesats. Conventional solid
      state based magnetometers pose a viable solution, though many are prone to
      radiation damage and plagued with temperature instabilities. In this work, we
      report on the development of a new self-calibrating, solid-state based
      magnetometer which measures magnetic field induced changes in current within a
      SiC pn junction caused by the interaction of external magnetic fields with the
      atomic scale defects intrinsic to the semiconductor. Unlike heritage designs, the
      magnetometer does not require inductive sensing elements, high frequency radio,
      and/or optical circuitry and can be made significantly more compact and
      lightweight, thus enabling missions leveraging swarms of cubesats capable of
      science returns not possible with a single large-scale satellite. Additionally,
      the robustness of the SiC semiconductor allows for operation in extreme
      conditions such as the hot Venusian surface and the high radiation environment of
      the Jovian system.

PMID- 27892523
TI  - Ultraviolet optomechanical crystal cavities with ultrasmall modal mass and high
      optomechanical coupling rate.
AB  - Optomechanical crystal (OMC) cavities which exploit the simultaneous photonic and
      phononic bandgaps in periodic nanostructures have been utilized to colocalize,
      couple, and transduce optical and mechanical resonances for nonlinear
      interactions and precision measurements. The development of near-infrared OMC
      cavities has difficulty in maintaining a high optomechanical coupling rate when
      scaling to smaller mechanical modal mass because of the reduction of the spatial
      overlap between the optical and mechanical modes. Here, we explore OMC nanobeam
      cavities in gallium nitride operating at the ultraviolet wavelengths to overcome
      this problem. With a novel optimization strategy, we have successfully designed
      an OMC cavity, with a size of 3.83 * 0.17 * 0.13 MUm3 and the mechanical modal
      mass of 22.83 fg, which possesses an optical mode resonating at the wavelength of
      393.03 nm and the fundamental mechanical mode vibrating at 14.97 GHz. The
      radiation-limited optical Q factor, mechanical Q factor, and optomechanical
      coupling rate are 2.26 * 107, 1.30 * 104, and 1.26 MHz, respectively. Our design
      and optimization approach can also serve as the general guidelines for future
      development of OMC cavities with improved device performance.

PMID- 27892522
TI  - SARS-CoV fusion peptides induce membrane surface ordering and curvature.
AB  - Viral membrane fusion is an orchestrated process triggered by membrane-anchored
      viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe
      acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains
      called fusion peptides (FP) that play essential roles in virus entry. Although
      membrane fusion has been broadly studied, there are still major gaps in the
      molecular details of lipid rearrangements in the bilayer during fusion peptide
      membrane interactions. Here we employed differential scanning calorimetry (DSC)
      and electron spin resonance (ESR) to gather information on the membrane fusion
      mechanism promoted by two putative SARS FPs. DSC data showed the peptides
      strongly perturb the structural integrity of anionic vesicles and support the
      hypothesis that the peptides generate opposing curvature stresses on
      phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid
      packing and head group ordering as well as reduce the intramembrane water content
      for anionic membranes. Therefore, bending moment in the bilayer could be
      generated, promoting negative curvature. The significance of the ordering effect,
      membrane dehydration, changes in the curvature properties and the possible role
      of negatively charged phospholipids in helping to overcome the high kinetic
      barrier involved in the different stages of the SARS-CoV-mediated membrane fusion
      are discussed.

PMID- 27892525
TI  - SXT/R391 integrative and conjugative elements in Proteus species reveal abundant
      genetic diversity and multidrug resistance.
AB  - SXT/R391 integrative and conjugative elements (ICEs) are self-transmissible
      mobile genetic elements that are found in most members of Enterobacteriaceae.
      Here, we determined fifteen SXT/R391 ICEs carried by Proteus isolates from food
      (4.2%) and diarrhoea patients (17.3%). BLASTn searches against GenBank showed
      that the fifteen SXT/R391 ICEs were closely related to that from different
      Enterobacteriaceae species, including Proteus mirabilis. Using core gene
      phylogenetic analysis, the fifteen SXT/R391 ICEs were grouped into six distinct
      clusters, including a dominant cluster and three clusters that have not been
      previously reported in Proteus isolates. The SXT/R391 ICEs shared a common
      structure with a set of conserved genes, five hotspots and two variable regions,
      which contained more foreign genes, including drug-resistance genes. Notably, a
      class A beta-lactamase gene was identified in nine SXT/R391 ICEs. Collectively,
      the ICE-carrying isolates carried resistance genes for 20 tested drugs. Six
      isolates were resistant to chloramphenicol, kanamycin, streptomycin, trimethoprim
      sulfamethoxazole, sulfisoxazole and tetracycline, which are drug resistances
      commonly encoded by ICEs. Our results demonstrate abundant genetic diversity and
      multidrug resistance of the SXT/R391 ICEs carried by Proteus isolates, which may
      have significance for public health. It is therefore necessary to continuously
      monitor the antimicrobial resistance and related mobile elements among Proteus
      isolates.

PMID- 27892526
TI  - Comprehensive Gene expression meta-analysis and integrated bioinformatic
      approaches reveal shared signatures between thrombosis and myeloproliferative
      disorders.
AB  - Thrombosis is a leading cause of morbidity and mortality in patients with
      myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and
      essential thrombocythemia (ET). Despite the attempts to establish a link between
      them, the shared biological mechanisms are yet to be characterized. An integrated
      gene expression meta-analysis of five independent publicly available microarray
      data of the three diseases was conducted to identify shared gene expression
      signatures and overlapping biological processes. Using INMEX bioinformatic tool,
      based on combined Effect Size (ES) approaches, we identified a total of 1,157
      differentially expressed genes (DEGs) (697 overexpressed and 460 underexpressed
      genes) shared between the three diseases. EnrichR tool's rich library was used
      for comprehensive functional enrichment and pathway analysis which revealed "mRNA
      Splicing" and "SUMO E3 ligases SUMOylate target proteins" among the most enriched
      terms. Network based meta-analysis identified MYC and FN1 to be the most highly
      ranked hub genes. Our results reveal that the alterations in biomarkers of the
      coagulation cascade like F2R, PROS1, SELPLG and ITGB2 were common between the
      three diseases. Interestingly, the study has generated a novel database of
      candidate genetic markers, pathways and transcription factors shared between
      thrombosis and MPDs, which might aid in the development of prognostic therapeutic
      biomarkers.

PMID- 27892527
TI  - Abnormal Hypermethylation of the VDAC2 Promoter is a Potential Cause of
      Idiopathic Asthenospermia in Men.
AB  - This study aimed to explore the association between the methylation status of the
      VDAC2 gene promoter region and idiopathic asthenospermia (IAS). Twenty-five IAS
      patients and 27 fertile normozoospermia (NZ) were involved. GC-2spd cells were
      treated with different concentrations of 5-aza-2'-deoxycytidine (5-Aza-CdR) for
      24 h and 48 h. qRT-PCR was conducted to reveal whether or not VDAC2 expression
      was regulated by methylated modification. A dual-luciferase activity detection
      was used to verify VDAC2 promoter activity in GC-2spd cells. Bisulphite genomic
      sequence was used to analyse DNA methylation of the VDAC2 promoter. The results
      showed that VDAC2 expression was significantly increased after treated with 5-Aza
      CdR. A strong activity of the promoter (-2000 bp to +1000 bp) was detected by
      dual-luciferase activity detection (P < 0.05). The bisulphite genomic sequencing
      and correlation analysis showed that sperm motility was positively associated
      with the methylation pattern of uncomplete methylation and mild hypermethylation,
      and negatively related to the percentage of moderate methylation. In conclusion,
      high methylation of the VDAC2 promoter CpGs could be positively correlated with
      low sperm motility. Abnormal methylation of VDAC2 promoter may be a potential
      cause to idiopathic asthenospermia.

PMID- 27892528
TI  - Sphingomyelin generated by sphingomyelin synthase 1 is involved in attachment and
      infection with Japanese encephalitis virus.
AB  - Japanese encephalitis virus (JEV) is a mosquito-borne RNA virus which infects
      target cells via the envelope protein JEV-E. However, its cellular targets are
      largely unknown. To investigate the role of sphingomyelin (SM) in JEV infection,
      we utilized SM-deficient immortalized mouse embryonic fibroblasts (tMEF)
      established from SM synthase 1 (SMS1)/SMS2 double knockout mice. SMS deficiency
      significantly reduced both intracellular and extracellular JEV levels at 48 h
      after infection. Furthermore, after 15 min treatment with JEV, the early steps of
      JEV infection such as attachment and cell entry were also diminished in SMS
      deficient tMEFs. The inhibition of JEV attachment and infection were recovered by
      overexpression of SMS1 but not SMS2, suggesting SMS1 contributes to SM production
      for JEV attachment and infection. Finally, intraperitoneal injection of JEV into
      SMS1-deficient mice showed an obvious decrease of JEV infection and its
      associated pathologies, such as meningitis, lymphocyte infiltration, and
      elevation of interleukin 6, compared with wild type mice. These results suggest
      that SMS1-generated SM on the plasma membrane is related in JEV attachment and
      subsequent infection, and may be a target for inhibition of JEV infection.

PMID- 27892529
TI  - A peptidoglycan recognition protein acts in whitefly (Bemisia tabaci) immunity
      and involves in Begomovirus acquisition.
AB  - Peptidoglycan recognition proteins (PGRPs) are multifunctional pattern
      recognition proteins. Here, we report that a PGRP gene, BtPGRP, encodes a PGRP
      from the whitefly Bemisia tabaci (MEAM1) that binds and kills bacteria in vitro.
      We analyzed BtPGRP transcriptional profiling, and the distribution of the cognate
      protein within the midgut. Fungal infection and wasp parasitization induced
      expression of BtPGRP. Silencing BtPGRP with artificial media amended with dsRNA
      led to reduced expression of a gene encoding an antimicrobial peptide, B. tabaci
      c-type lysozyme. Begomovirus infection also led to increased expression of
      BtPGRP. We propose that BtPGRP has a potential Tomato yellow leaf curl virus
      (TYLCV) binding site because we detected in vitro interaction between BtPGRP and
      TYLCV by immunocapture PCR, and recorded the co-localization of TYLCV and BtPGRP
      in midguts. This work addresses a visible gap in understanding whitefly immunity
      and provides insight into how the whitefly immunity acts in complex mechanisms of
      Begomovirus transmission among plants.

PMID- 27892531
TI  - A genome-wide association study identifies a horizontally transferred bacterial
      surface adhesin gene associated with antimicrobial resistant strains.
AB  - Carbapenems are a class of last-resort antibiotics; thus, the increase in
      bacterial carbapenem-resistance is a serious public health threat. Acinetobacter
      baumannii is one of the microorganisms that can acquire carbapenem-resistance; it
      causes severe nosocomial infection, and is notoriously difficult to control in
      hospitals. Recently, a machine-learning approach was first used to analyze the
      genome sequences of hundreds of susceptible and resistant A. baumannii strains,
      including those carrying commonly acquired resistant mechanisms, to build a
      classifier that can predict strain resistance. A complementary approach is to
      explore novel genetic elements that could be associated with the antimicrobial
      resistance of strains, independent of known mechanisms. Therefore, we carefully
      selected A. baumannii strains, spanning various genotypes, from public genome
      databases, and conducted the first genome-wide association study (GWAS) of
      carbapenem resistance. We employed a recently developed method, capable of
      identifying any kind of genetic variation and accounting for bacterial population
      structure, and evaluated its effectiveness. Our study identified a surface
      adhesin gene that had been horizontally transferred to an ancestral branch of A.
      baumannii, as well as a specific region of that gene that appeared to accumulate
      multiple individual variations across the different branches of carbapenem
      resistant A. baumannii strains.

PMID- 27892530
TI  - Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular
      geometry.
AB  - The anatomic and functional combinations of cusps and lophs (ridges) define the
      tooth shape of rodent molars, which distinguishes species. The species-specific
      cusp patterns result from the spatiotemporal induction of enamel knots (EKs),
      which require precisely controlled cellular behavior to control the epithelial
      invagination. Despite the well-defined roles of EK in cusp patterning, the
      determinants of the ultimate cuspal shapes and involvement of epithelial cellular
      geometry are unknown. Using two typical tooth patterns, the lophodont in gerbils
      and the bunodont in mice, we showed that the cuspal shape is determined by the
      dental epithelium at the cap stage, whereas the cellular geometry in the inner
      dental epithelium (IDE) is correlated with the cuspal shape. Intriguingly, fine
      tuning Rac1 and RhoA interconvert cuspal shapes between two species by remolding
      the cellular geometry. Either inhibition of Rac1 or ectopic expression of RhoA
      could region-distinctively change the columnar shape of IDE cells in gerbils to
      drive invagination to produce cusps. Conversely, RhoA reduction in mice inhibited
      invagination and developed lophs. Furthermore, we found that Rac1 and RhoA
      modulate the choices of cuspal shape by coordinating adhesion junctions, actin
      distribution, and fibronectin localization to drive IDE invagination.

PMID- 27892532
TI  - Si doped T6 carbon structure as an anode material for Li-ion batteries: An ab
      initio study.
AB  - First-principles calculations are performed to identify the pristine and Si doped
      3D metallic T6 carbon structure (having both sp2 and sp3 type hybridization) as a
      new carbon based anode material. The pi electron of C2 atoms (sp2 bonded) forms
      an out of plane network that helps to capture the Li atom. The highest Li storage
      capacity of Si doped T6 structure with conformation Li1.7Si1C5 produces
      theoretical specific capacity of 632 mAh/g which substantially exceeding than
      graphite. Also, open-circuit voltage (OCV) with respect to Li metal shows large
      negative when compared to the pristine T6 structure. This indicates modifications
      in terms of chemical properties are required in anode materials for practical
      application. Among various doped (Si, Ge, Sn, B, N) configuration, Si doped T6
      structure provides a stable positive OCV for high Li concentrations. Likewise,
      volume expansion study also shows Si doped T6 structure is more stable with less
      pulverization and substantial capacity losses in comparison with graphite and
      silicon as an anode materials. Overall, mixed hybridized (sp2 + sp3) Si doped T6
      structure can become a superior anode material than present sp2 hybridized
      graphite and sp3 hybridized Si structure for modern Lithium ion batteries.

PMID- 27892533
TI  - Small-sized, stable lipid nanoparticle for the efficient delivery of siRNA to
      human immune cell lines.
AB  - Gene silencing by small interfering RNA (siRNA) is useful for analyzing the
      functions of human immune cells. However, the transfection of siRNA to human
      immune cells is difficult. Here, we used a multifunctional envelope-type
      nanodevice (MEND) containing YSK12-C4 (YSK12-MEND) to efficiently introduce siRNA
      to human immune cell lines, Jurkat, THP-1, KG-1 and NK92. The YSK12-MEND was
      transfected to human immune cell lines at a siRNA dose range of 1-30 nM,
      resulting that maximum gene silencing efficiencies at the mRNA level in Jurkat,
      THP-1, KG-1 and NK92 were 96%, 96%, 91% and 75%, respectively. The corresponding
      values for Lipofectamine RNAiMAX (RNAiMAX) were 37%, 56%, 43% and 19%,
      respectively. The process associated with cellular uptake played a role in
      effective gene silencing effect of the YSK12-MEND. The small size and high non
      aggregability of the YSK12-MEND were advantageous for the cellular
      internalization of siRNA to immune cell lines. In the case of RNAiMAX, a drastic
      increase in particles size was observed in the medium used, which inhibited
      cellular uptake. The YSK12-MEND reported in herein appears to be appropriate for
      delivering siRNA to human immune cells, and the small particle size and non
      aggregability are essential properties.

PMID- 27892534
TI  - Improving Estimation of Fiber Orientations in Diffusion MRI Using Inter-Subject
      Information Sharing.
AB  - Diffusion magnetic resonance imaging is widely used to investigate diffusion
      patterns of water molecules in the human brain. It provides information that is
      useful for tracing axonal bundles and inferring brain connectivity. Diffusion
      axonal tracing, namely tractography, relies on local directional information
      provided by the orientation distribution functions (ODFs) estimated at each
      voxel. To accurately estimate ODFs, data of good signal-to-noise ratio and
      sufficient angular samples are desired. This is however not always available in
      practice. In this paper, we propose to improve ODF estimation by using inter
      subject image correlation. Specifically, we demonstrate that diffusion-weighted
      images acquired from different subjects can be transformed to the space of a
      target subject to drastically increase the number of angular samples to improve
      ODF estimation. This is largely due to the incoherence of the angular samples
      generated when the diffusion signals are reoriented and warped to the target
      space. To reorient the diffusion signals, we propose a new spatial normalization
      method that directly acts on diffusion signals using local affine transforms.
      Experiments on both synthetic data and real data show that our method can reduce
      noise-induced artifacts, such as spurious ODF peaks, and yield more coherent
      orientations.

PMID- 27892535
TI  - Climate-driven increase of natural wetland methane emissions offset by human
      induced wetland reduction in China over the past three decades.
AB  - Both anthropogenic activities and climate change can affect the biogeochemical
      processes of natural wetland methanogenesis. Quantifying possible impacts of
      changing climate and wetland area on wetland methane (CH4) emissions in China is
      important for improving our knowledge on CH4 budgets locally and globally.
      However, their respective and combined effects are uncertain. We incorporated
      changes in wetland area derived from remote sensing into a dynamic CH4 model to
      quantify the human and climate change induced contributions to natural wetland
      CH4 emissions in China over the past three decades. Here we found that human
      induced wetland loss contributed 34.3% to the CH4 emissions reduction (0.92
      TgCH4), and climate change contributed 20.4% to the CH4 emissions increase (0.31
      TgCH4), suggesting that decreasing CH4 emissions due to human-induced wetland
      reductions has offset the increasing climate-driven CH4 emissions. With climate
      change only, temperature was a dominant controlling factor for wetland CH4
      emissions in the northeast (high latitude) and Qinghai-Tibet Plateau (high
      altitude) regions, whereas precipitation had a considerable influence in relative
      arid north China. The inevitable uncertainties caused by the asynchronous for
      different regions or periods due to inter-annual or seasonal variations among
      remote sensing images should be considered in the wetland CH4 emissions
      estimation.

PMID- 27892537
TI  - Gaussian entanglement generation from coherence using beam-splitters.
AB  - The generation and quantification of quantum entanglement is crucial for quantum
      information processing. Here we study the transition of Gaussian correlation
      under the effect of linear optical beam-splitters. We find the single-mode
      Gaussian coherence acts as the resource in generating Gaussian entanglement for
      two squeezed states as the input states. With the help of consecutive beam
      splitters, single-mode coherence and quantum entanglement can be converted to
      each other. Our results reveal that by using finite number of beam-splitters, it
      is possible to extract all the entanglement from the single-mode coherence even
      if the entanglement is wiped out before each beam-splitter.

PMID- 27892536
TI  - Investigation of Cell-Substrate Adhesion Properties of Living Chondrocyte by
      Measuring Adhesive Shear Force and Detachment Using AFM and Inverse FEA.
AB  - It is well-known that cell adhesion is important in many biological processes
      such as cell migration and proliferation. A better understanding of the cell
      adhesion process will shed insight into these cellular biological responses as
      well as cell adhesion-related diseases treatment. However, there is little
      research which has attempted to investigate the process of cell adhesion and its
      mechanism. Thus, this paper aims to study the time-dependent adhesion properties
      of single living chondrocytes using an advanced coupled experimental-numerical
      approach. Atomic Force Microscopy (AFM) tips will be used to apply lateral forces
      to detach chondrocytes that are seeded for three different periods. An advanced
      Finite Element Analysis (FEA) model combining porohyperelastic (PHE) constitutive
      model and cohesive zone formulation is developed to explore the mechanism of
      adhesion. The results revealed that the cells can resist normal traction better
      than tangential traction in the beginning of adhesion. This is when the cell
      adhesion molecules establish early attachment to the substrates. After that when
      the cells are spreading, stress fiber bundles generate tangential traction on the
      substrate to form strong adhesion. Both simulation and experimental results agree
      well with each other, providing a powerful tool to study the cellular adhesion
      process.

PMID- 27892539
TI  - Chemotypic variation in terpenes emitted from storage pools influences early
      aphid colonisation on tansy.
AB  - Tansy plants (Tanacetum vulgare L.) exhibit high chemical variation, particularly
      in mono- and sesquiterpenes that are stored in specialised glands on the plant
      surface. In the present work we investigated the effects of terpene chemotypes on
      Metopeurum fuscoviride, an aphid species specialised on tansy, and their tending
      ants, at the field scale. Previous studies have chemotyped tansy by assessing
      dominant compounds; here we propose a method of chemotyping using all volatile
      compounds that are likely emitted from the storage glands. The analysis is based
      on two extraction methods: GC-MS analysis of leaf hexane extracts and SBSE
      analysis of headspace emissions. In an initial screening we identified the subset
      of compounds present in both chemical patterns, labelled as 'compounds likely
      emitted from storage'. In a large field survey we could show that the putative
      chemotypic emission pattern from storage pools significantly affected the early
      aphid colonisation of tansy. Moreover, the statistical analyses revealed that
      minor compounds exerted a stronger influence on aphid and tending-ant presence
      than dominant compounds. Overall we demonstrated that within the enormous
      chemotypic variation of terpenes in tansy plants, chemical signatures of volatile
      terpenes can be related to the occurrence of insects on individual plants in the
      field.

PMID- 27892538
TI  - Helicobacter pylori is associated with dyslipidemia but not with other risk
      factors of cardiovascular disease.
AB  - Epidemiologic and clinical data suggest that Helicobacter pylori infection is a
      contributing factor in the progression of atherosclerosis. However, the specific
      cardiovascular disease risk factors associated with H. pylori remain unclear. We
      performed a cross-sectional study of 37,263 consecutive healthy subjects who
      underwent a routine health check-up. In multivariable log Poisson regression
      models adjusted for potential confounders, the associations of H. pylori
      seropositivity with higher LDL-C (relative risk [RR], 1.21; 95% confidence
      interval [CI], 1.12-1.30) and lower HDL-C level (RR, 1.10; 95% CI, 1.01-1.18)
      were significant and independent. In multiple linear regression analyses, H.
      pylori infection was significantly associated with higher total cholesterol level
      (coefficient = 2.114, P < 0.001), higher LDL-C level (coefficient = 3.339, P <
      0.001), lower HDL-C level (coefficient = -1.237, P < 0.001), and higher diastolic
      blood pressure (coefficient = 0.539, P = 0.001). In contrast, H. pylori infection
      was not associated with obesity-related parameters (body mass index, waist
      circumference), glucose tolerance (fasting glucose, glycated hemoglobin), and
      systolic blood pressure. We found that H. pylori infection was significantly and
      independently associated with dyslipidemia, but not with other cardiometabolic
      risk factors, after adjusting for potential risk factors of atherosclerosis.

PMID- 27892540
TI  - Pancreatic Mesenchyme Regulates Islet Cellular Composition in a Patched/Hedgehog
      Dependent Manner.
AB  - Pancreas development requires restrained Hedgehog (Hh) signaling activation.
      While deregulated Hh signaling in the pancreatic mesenchyme has been long
      suggested to be detrimental for proper organogenesis, this association was not
      directly shown. Here, we analyzed the contribution of mesenchymal Hh signaling to
      pancreas development. To increase Hh signaling in the pancreatic mesenchyme of
      mouse embryos, we deleted Patched1 (Ptch1) in these cells. Our findings indicate
      that deregulated Hh signaling in mesenchymal cells was sufficient to impair
      pancreas development, affecting both endocrine and exocrine cells. Notably,
      transgenic embryos displayed disrupted islet cellular composition and morphology,
      with a reduced beta-cell portion. Our results indicate that the cell-specific
      growth rates of alpha- and beta-cell populations, found during normal
      development, require regulated mesenchymal Hh signaling. In addition, we detected
      hyperplasia of mesenchymal cells upon elevated Hh signaling, accompanied by them
      acquiring smooth-muscle like phenotype. By specifically manipulating mesenchymal
      cells, our findings provide direct evidence for the non-autonomous roles of the
      Hh pathway in pancreatic epithelium development. To conclude, we directly show
      that regulated mesenchymal Hh signaling is required for pancreas organogenesis
      and establishment of its proper cellular composition.

PMID- 27892541
TI  - Multi-strategy genome-wide association studies identify the DCAF16-NCAPG region
      as a susceptibility locus for average daily gain in cattle.
AB  - Average daily gain (ADG) is the most economically important trait in beef cattle
      industry. Using genome-wide association study (GWAS) approaches, previous studies
      have identified several causal variants within the PLAG1, NCAPG and LCORL genes
      for ADG in cattle. Multi-strategy GWASs were implemented in this study to improve
      detection and to explore the causal genes and regions. In this study, we
      conducted GWASs based on the genotypes of 1,173 Simmental cattle. In the SNP
      based GWAS, the most significant SNPs (rs109303784 and rs110058857, P = 1.78 * 10
      7) were identified in the NCAPG intron on BTA6 and explained 4.01% of the
      phenotypic variance, and the independent and significant SNP (rs110406669, P =
      5.18 * 10-6) explained 3.32% of the phenotypic variance. Similarly, in the
      haplotype-based GWAS, the most significant haplotype block, Hap-6-N1416 (P = 2.56
      * 10-8), spanned 12.7 kb on BTA6 and explained 4.85% of the phenotypic variance.
      Also, in the gene-based GWAS, seven significant genes were obtained which
      included DCAF16 and NCAPG. Moreover, analysis of the transcript levels confirmed
      that transcripts abundance of NCAPG (P = 0.046) and DCAF16 (P = 0.046) were
      significantly correlated with the ADG trait. Overall, our results from the multi
      strategy GWASs revealed the DCAF16-NCAPG region to be a susceptibility locus for
      ADG in cattle.

PMID- 27892542
TI  - Streptococcus pneumoniae disrupts pulmonary immune defence via elastase release
      following pneumolysin-dependent neutrophil lysis.
AB  - Streptococcus pneumoniae is a leading cause of bacterial pneumonia and is the
      principal cause of morbidity and mortality worldwide. Previous studies suggested
      that excessive activation of neutrophils results in the release of neutrophil
      elastase, which contributes to lung injury in severe pneumonia. Although both
      pneumococcal virulence factors and neutrophil elastase contribute to the
      development and progression of pneumonia, there are no studies analysing
      relationships between these factors. Here, we showed that pneumolysin, a
      pneumococcal pore-forming toxin, induced cell lysis in primary isolated human
      neutrophils, leading to the release of neutrophil elastase. Pneumolysin exerted
      minimal cytotoxicity against alveolar epithelial cells and macrophages, whereas
      neutrophil elastase induced detachment of alveolar epithelial cells and impaired
      phagocytic activity in macrophages. Additionally, activation of neutrophil
      elastase did not exert bactericidal activity against S. pneumoniae in vitro. P2X7
      receptor, which belongs to a family of purinergic receptors, was involved in
      pneumolysin-induced cell lysis. These findings suggested that infiltrated
      neutrophils are the primary target cells of pneumolysin, and that S. pneumoniae
      exploits neutrophil-elastase leakage to induce the disruption of pulmonary immune
      defences, thereby causing lung injury.

PMID- 27892543
TI  - Functional and Structural Signatures of the Anterior Insula are associated with
      Risk-taking Tendency of Analgesic Decision-making.
AB  - In a medical context, decision-making is associated with complicated assessment
      of gains, losses and uncertainty of outcomes. We here provide novel evidence
      about the brain mechanisms underlying decision-making of analgesic treatment.
      Thirty-six healthy participants were recruited and completed the Analgesic
      Decision-making Task (ADT), which quantified individual tendency of risk-taking
      (RPI), as the frequency of choosing a riskier option to relieve pain. All the
      participants received resting-state (rs) functional magnetic resonance imaging
      (MRI) and structural MRI. On rs-functional connectome, degree centrality (DC) of
      the bilateral anterior insula (aINS) was positively correlated with the RPI. The
      functional connectivity between the aINS, the nucleus accumbens and multiple
      brain regions, predominantly the medial frontal cortex, was positively correlated
      with the RPI. On structural signatures, the RPI was positively correlated with
      grey matter volume at the right aINS, and such an association was mediated by DC
      of the left aINS. Regression analyses revealed that both DC of the left aINS and
      participants' imagined pain relief, as the utility of pain reduction, could
      predict the individual RPI. The findings suggest that the functional and
      structural brain signature of the aINS is associated with the individual
      differences of risk-taking tendency in the context of analgesic decision-making.

PMID- 27892544
TI  - Boron-doped diamond semiconductor electrodes: Efficient photoelectrochemical CO2
      reduction through surface modification.
AB  - Competitive hydrogen evolution and multiple proton-coupled electron transfer
      reactions limit photoelectrochemical CO2 reduction in aqueous electrolyte. Here,
      oxygen-terminated lightly boron-doped diamond (BDDL) thin films were synthesized
      as a semiconductor electron source to accelerate CO2 reduction. However, BDDL
      alone could not stabilize the intermediates of CO2 reduction, yielding a
      negligible amount of reduction products. Silver nanoparticles were then deposited
      on BDDL because of their selective electrochemical CO2 reduction ability.
      Excellent selectivity (estimated CO:H2 mass ratio of 318:1) and recyclability
      (stable for five cycles of 3 h each) for photoelectrochemical CO2 reduction were
      obtained for the optimum silver nanoparticle-modified BDDL electrode at -1.1 V
      vs. RHE under 222-nm irradiation. The high efficiency and stability of this
      catalyst are ascribed to the in situ photoactivation of the BDDL surface during
      the photoelectrochemical reaction. The present work reveals the potential of BDDL
      as a high-energy electron source for use with co-catalysts in photochemical
      conversion.

PMID- 27892545
TI  - Erythrocyte membrane based cationic polymer-mcDNA complexes as an efficient gene
      delivery system.
AB  - Gene therapy has great promise for the treatment of obtained and inherited
      serious diseases. However, the lack of safe and efficient gene delivery systems
      remains a barrier for their clinical application. Here, we reported a potential
      gene delivery vehicle composed of the erythrocyte membrane and cationic polymers,
      for example the XtremeGENE from Roche and the epsilon-caprolactone modified
      polyethylenimine. In addition to high efficiency, this system showed negligible
      cytotoxicity compared to the two cationic polymers alone in various cell lines,
      including human embryonic kidney cells (293T), human liver cancer cells (Huh7 and
      HepG2), murine dendritic cells (DC2.4) and human umbilical cord mesenchymal stem
      cells (Hu-MSCs). Moreover, the results of confocal laser scanning microscopy and
      flow cytometry suggested that the cell uptake of this gene vector was improved
      and might be introduced by the fusion interaction between the erythrocyte
      membrane and targeted cells.Thus, all the results revealed that the erythrocyte
      membrane based gene delivery system might be able to serve as an excellent gene
      delivery system.

PMID- 27892549
TI  - Hydrogen-bonding catalysis of sulfonium salts.
AB  - Although quaternary ammonium and phosphonium salts are known as important
      catalysts in phase-transfer catalysis, the catalytic ability of tertiary
      sulfonium salts has not yet been well demonstrated. Herein, we demonstrate the
      catalytic ability of trialkylsulfonium salts as hydrogen-bonding catalysts on the
      basis of the characteristic properties of the acidic alpha hydrogen atoms on
      alkylsulfonium salts.

PMID- 27892550
TI  - Multifunctional and robust composite materials comprising gold nanoparticles at a
      spherical polystyrene particle surface.
AB  - The preparation of a family of composite particles comprising gold nanoparticles
      (AuNP) assembled at a polystyrene (PS) surface is reported. Tunable loading is
      demonstrated for AuNP sizes (4.5-26 nm). The robust composites are stable to
      multiple centrifugation and dispersion cycles and to conditions of high ionic
      strength, physiological buffer and cell culture media. These properties provide
      potential for a variety of applications from cellular studies to catalysis.

PMID- 27892551
TI  - Cascade photoredox/gold catalysis: access to multisubstituted indoles via
      aminoarylation of alkynes.
AB  - A new method for the synthesis of 3-arylindoles has been developed by visible
      light mediated dual gold/photoredox catalysis. This transformation has many
      features such as cascade catalysis, high efficiency, redox-neutral reaction
      conditions and good functional group tolerance. The reaction proceeds through the
      photoredox-promoted formation of an electrophilic arylgold(iii) intermediate that
      undergoes coupling with the arylamine nucleophile.

PMID- 27892552
TI  - Lessons learned in tuning the optoelectronic properties of phosphorescent
      iridium(iii) complexes.
AB  - This perspective illustrates our approach in the design of heteroleptic cationic
      iridium(iii) complexes for optoelectronic applications, especially as emitters in
      electroluminescent devices. We discuss changes in the photophysical properties of
      the complexes as a consequence of modification of the electronics of either the
      cyclometalating (C^N) or the ancillary (N^N) ligands. We then broach the impact
      on these properties as a function of modification of the structure of both types
      of ligands. We explain trends in the optoelectronic behaviour of the complexes
      using a combination of rationally designed structure-property relationship
      studies and theoretical modelling that serves to inform subsequent ligand design.
      However, we have found cases where the design paradigms do not always hold true.
      Nevertheless, all these studies contribute to the lessons we have learned in the
      design of heteroleptic cationic phosphorescent iridium(iii) complexes.

PMID- 27892553
TI  - Photochemical CO2 reduction in water using a co-immobilised nickel catalyst and a
      visible light sensitiser.
AB  - A dye-sensitised CO2 reduction photocatalyst that operates in water is reported.
      Transient spectroscopy demonstrates that the facile co-immobilisation of a Ru dye
      and a Ni CO2 reduction electrocatalyst enables efficient on-particle electron
      transfer leading to photocatalytic activity that greatly exceeds the equivalent
      solution based system.

PMID- 27892554
TI  - An alpha-helical peptidomimetic scaffold for dynamic combinatorial library
      formation.
AB  - A novel oligobenzamide-based alpha-helix mimetic was designed and synthesised
      with either imine or hydrazone functionalities that serve both to pre-organise
      the side-chain vectors to mimic the i, i + 4 and i + 7 residues of an alpha
      helix, and to allow for the facile creation of dynamic libraries.

PMID- 27892555
TI  - One-pot synthesis of micron partly hollow anisotropic dumbbell shaped silica core
      shell particles.
AB  - A facile method is described to prepare micron partly hollow dumbbell silica
      particles in a single step. The obtained particles consist of a large dense part
      and a small hollow lobe. The spherical dense core as well as the hollow lobe are
      covered by mesoporous channels. In the case of the smaller lobe these channels
      are responsible for the permeability of the shell which was demonstrated by
      confocal imaging and spectroscopy.

PMID- 27892556
TI  - Thermal decomposition of ammonium hexachloroosmate.
AB  - Structural changes of (NH4)2[OsCl6] occurring during thermal decomposition in a
      reduction atmosphere have been studied in situ using combined energy-dispersive X
      ray absorption spectroscopy (ED-XAFS) and powder X-ray diffraction (PXRD).
      According to PXRD, (NH4)2[OsCl6] transforms directly to metallic Os without the
      formation of any crystalline intermediates but through a plateau where no
      reactions occur. XANES and EXAFS data by means of Multivariate Curve Resolution
      (MCR) analysis show that thermal decomposition occurs with the formation of an
      amorphous intermediate {OsCl4}x with a possible polymeric structure. Being
      revealed for the first time the intermediate was subjected to determine the local
      atomic structure around osmium. The thermal decomposition of hexachloroosmate is
      much more complex and occurs within a minimum two-step process, which has never
      been observed before.

PMID- 27892557
TI  - Dipolar molecules inside C70: an electric field-driven room-temperature single
      molecule switch.
AB  - We propose a two-state electric field-driven room-temperature single-molecule
      switch based on a dipolar molecule enclosed inside ellipsoidal fullerene C70. We
      show that the two low-energy minima of the molecular dipole inside the C70 cage
      provide distinguishable molecular states of the system that can be switched by
      application of an external electric field.

PMID- 27892558
TI  - Synthesis and reductive elimination of arylPd(ii) trifluoromethyl complexes: a
      remarkable concentration effect on chemoselectivity.
AB  - Reductive elimination from Pd(ii) aryl trifluoromethyl complexes is a challenging
      and elusive step which is accompanied by a number of kinetically more favorable
      side reactions giving rising to a complex mixture. We report herein the synthesis
      and isolation of several arylPd(ii) trifluoromethyl complexes (2a-c) and study
      their electronic structures, photophysical properties and reductive elimination
      reactivities. A remarkable concentration effect on chemoselectivity is observed
      for thermal decomposition of (Xantphos)Pd(ii)(Ar)(CF3) (2c) that favors the
      formation of Ar-CF3 at lower concentrations, but gives increasingly more Ar-Ar
      homocoupling product to a dominant extent as the concentration of 2c increases.
      This is solid evidence for the involvement of an intermolecular Ar/CF3 ligand
      exchange/Ar-Ar reductive elimination mechanism that has been proposed based on
      DFT computational studies. The interplay between theory and experiment provides
      valuable insights into the mechanism and kinetics of the key elementary reaction
      of reductive elimination at Pd(ii), and may thus prompt the design of more
      efficient Pd-mediated nucleophilic trifluoromethylation reactions.

PMID- 27892559
TI  - Insights into bonding interactions and excitation energies of 3d-4f mixed
      lanthanide transition metal macrocyclic complexes.
AB  - In this contribution, a computational study of equatorial bound tetranuclear
      macrocycle (butylene linked) [LnZn(HOMBu)]3+ (Ln = La3+, Ce3+) complexes was
      carried out. Here, the electronic structure, bonding interaction and excitation
      energies were studied within the relativistic density functional theory
      framework. From the electronic structure analysis, the frontier molecular
      orbitals (FMOs) were strongly localized in the d-orbitals of the Zn centers and
      the f-orbitals of the lanthanide ions. Besides, the inner MOs were found to
      exhibit a pi-character from the organic part of the macrocyclic chain. EDA-NOCV
      was used as a tool for evaluating the bonding interaction, taking the trinuclear
      metallomacrocycle (ZnHOMBu) and the lanthanide center as fragments. This analysis
      showed that the interaction between these fragments was slightly covalent; with
      this covalency being the result of a charge transfer from the metallomacrocyclic
      ring to the lanthanide. This phenomenon was observed in the deformation density
      channels obtained from the EDA-NOCV study; in which pi- and sigma-charge transfer
      was observed. Finally, the TD-DFT study of the excitation energies evidenced
      three sets of bands: the first set with the highest intensity represented the
      ligand to metal charge transfer bands; the second set could be attributed to the
      3d-4f electronic transitions between the metal centers; and the third set
      represented the f-f bands found for the open-shell cerium complex. This class of
      complexes accomplishes the "antenna effect" principle, which states that highly
      absorptive transition-metal (TM) complexes can be used to enhance the
      luminescence of poorly emissive systems, and are introduced in this study as self
      sensitizer bimetallic d-f systems with potential applications in near infra-red
      (NIR) technologies.

PMID- 27892560
TI  - Solution-phase synthesis of 1D tubular polymers via preorganization
      polymerization.
AB  - The synthesis of one-dimensional tubular polymers via a preorganization
      polymerization approach is presented. Prior to polymerization, photo-reactive
      monomers self-assemble into one-dimensional tubular structures in aqueous medium.
      The supramolecular polymers are subsequently converted into covalent polymers by
      light-induced anthracene dimerization.

PMID- 27892561
TI  - AIE fluorophore with enhanced cellular uptake for tracking esterase-activated
      release of taurine and ROS scavenging.
AB  - Fluorophores with aggregation-induced emission (AIE) characteristics are
      attractive and versatile tools for both chemical sensing and biological imaging.
      Herein, we designed and synthesized a fluorescent light-up system CTPE-Tau with
      enhanced cellular uptake ability. The system possesses several advantages, such
      as a large Stokes shift, low cytotoxicity, and good photostability. Also, it has
      been successfully utilized to track esterase-activated release of taurine and to
      scavenge intracellular ROS, and shows great potential for trackable visualized
      therapy.

PMID- 27892562
TI  - Aggregation-induced enhanced green light emission from a simple donor-pi-acceptor
      (D-pi-A) material: a structure-property relationship study.
AB  - Organic D-pi-A materials, possessing intramolecular charge transfer, have
      attracted much scientific attention in recent years because of their potential
      applications in the development of organic light emitting devices (OLEDs). Two
      new compounds, A1 and A2, having a D-pi-A skeleton have been synthesized and
      single crystals were grown by the solution growth technique. Both compounds were
      characterized for crystallographic, thermal and photophysical properties. Upon
      photo-excitation in the solid state, A1 showed very strong green light emission
      while A2 gave sky-blue emission with much lower intensity. A single crystal X-ray
      diffraction study revealed that in the crystal lattice of A1, both the donor and
      acceptor groups are involved in the intermolecular interactions. This results in
      the restricted intramolecular rotation (RIR) of the D and A moieties, and enables
      A1 to emit more intensely in the solid state due to aggregation-induced emission
      (AIE). Intense green light emission, along with a good crystalline nature
      indicates that A1 might be a potential candidate for opto-electronic devices.

PMID- 27892563
TI  - Using reference materials to improve the quality of data generated by USEPA
      analytical methods.
AB  - The quality of data generated for the analysis of environmental samples is
      critical to State and Federal regulatory agencies to ensure that decisions based
      upon the amounts of contaminants in environmental samples are truly protective of
      public health. The quality and validation of these measurements using the
      approved analytical methodology could be significantly enhanced by incorporating
      certified reference materials as part of the quality control protocols, yet this
      has not been widely implemented. Data from certified reference materials can
      provide critical information that can impact assessments regarding data use that
      is unavailable by other means. Using the analysis of Cr(vi) in soil extracts as
      the test case, some of the issues surrounding the use of certified reference
      materials for environmental applications are discussed in this paper, including
      the relative cost, and the availability and applicability regarding element
      coverage and content.

PMID- 27892564
TI  - Zirconia based dental ceramics: structure, mechanical properties,
      biocompatibility and applications.
AB  - Zirconia (ZrO2) based dental ceramics have been considered to be advantageous
      materials with adequate mechanical properties for the manufacturing of medical
      devices. Due to its very high compression strength of 2000 MPa, ZrO2 can resist
      differing mechanical environments. During the crack propagation on the
      application of stress on the surface of ZrO2, a crystalline modification
      diminishes the propagation of cracks. In addition, zirconia's biocompatibility
      has been studied in vivo, leading to the observation of no adverse response upon
      the insertion of ZrO2 samples into the bone or muscle. In vitro experimentation
      has exhibited the absence of mutations and good viability of cells cultured on
      this material leading to the use of ZrO2 in the manufacturing of hip head
      prostheses. The mechanical properties of zirconia fixed partial dentures (FPDs)
      have proven to be superior to other ceramic/composite restorations and hence
      leading to their significant applications in implant supported rehabilitations.
      Recent developments were focused on the synthesis of zirconia based dental
      materials. More recently, zirconia has been introduced in prosthetic dentistry
      for the fabrication of crowns and fixed partial dentures in combination with
      computer aided design/computer aided manufacturing (CAD/CAM) techniques. This
      systematic review covers the results of past as well as recent scientific studies
      on the properties of zirconia based ceramics such as their specific compositions,
      microstructures, mechanical strength, biocompatibility and other applications in
      dentistry.

PMID- 27892565
TI  - A highly sensitive and selective fluorescent probe for hypochlorite in pure water
      with aggregation induced emission characteristics.
AB  - As a reactive oxygen species (ROS), hypochlorite (OCl-) plays a crucial role in
      oxidative stress and signal transduction, controlling a wide range of
      physiological functions. In addition, the wide use of OCl- in the treatment of
      food and water might possibly threaten human health if the residual quantity was
      out of limits. Currently, sensitive methods employed to selectively monitor OCl-
      in aqueous samples in situ are still scarce and badly needed. Boron esters or
      acids are considered to be suitable functional groups for the detection of
      hydrogen peroxide due to their reliable reactivity. In this work, we try to
      develop a highly sensitive and selective OCl- probe (TPE2B) based on the
      mechanism of aggregation induced emission (AIE). Due to the distinct increase in
      water solubility of TPE2OH, which is generated from the reaction between TPE2B
      and OCl-, the strong emission of TPE2B is quenched dramatically. The response
      speed was as fast as 30 seconds with a detection limit as low as 28 nM.
      Additionally, test papers were also fabricated and exhibited a highly sensitive
      response to 0.1 mM OCl-.

PMID- 27892566
TI  - Water transport within carbon nanotubes on a wave.
AB  - Water molecules possess discontinuous properties in confined surroundings as
      compared to the bulk, their transport velocity shows a step change with the
      increase in the radius of hydrophobic carbon nanotubes (CNTs). Here, we report
      that the chain of water molecules in CNTs behaves as a "spring" owing to hydrogen
      bonding. Thus, the transport of water molecules in confined systems proceeds as a
      wave motion with eigen frequencies in the terahertz region which is determined by
      the CNT size. Water velocities derived from molecular dynamics (MD) fit well with
      the ones from finite element methods (FEM) on consideration of both the no-slip
      and slip boundary conditions for CNT diameters less than 1 nm and more than 1 nm,
      respectively. The present work helps clarify the features of mass and momentum
      transfers in confined surroundings, and provides perspectives for mass transfer
      applications.

PMID- 27892567
TI  - High-resolution two-field nuclear magnetic resonance spectroscopy.
AB  - Nuclear magnetic resonance (NMR) is a ubiquitous branch of spectroscopy that can
      explore matter at the scale of an atom. Significant improvements in sensitivity
      and resolution have been driven by a steady increase of static magnetic field
      strengths. However, some properties of nuclei may be more favourable at low
      magnetic fields. For example, transverse relaxation due to chemical shift
      anisotropy increases sharply at higher magnetic fields leading to line-broadening
      and inefficient coherence transfers. Here, we present a two-field NMR
      spectrometer that permits the application of rf-pulses and acquisition of NMR
      signals in two magnetic centres. Our prototype operates at 14.1 T and 0.33 T. The
      main features of this system are demonstrated by novel NMR experiments, in
      particular a proof-of-concept correlation between zero-quantum coherences at low
      magnetic field and single quantum coherences at high magnetic field, so that high
      resolution can be achieved in both dimensions, despite a ca. 10 ppm inhomogeneity
      of the low-field centre. Two-field NMR spectroscopy offers the possibility to
      circumvent the limits of high magnetic fields, while benefiting from their
      exceptional sensitivity and resolution. This approach opens new avenues for NMR
      above 1 GHz.

PMID- 27892568
TI  - Bulk molybdenum field emitters by inductively coupled plasma etching.
AB  - In this work we report on the fabrication of inductively coupled plasma (ICP)
      etched, diode-type, bulk molybdenum field emitter arrays. Emitter etching
      conditions as a function of etch mask geometry and process conditions were
      systematically investigated. For optimized uniformity, aspect ratios of >10 were
      achieved, with 25.5 nm-radius tips realised for masks consisting of aperture
      arrays some 4.45 MUm in diameter and whose field electron emission performance
      has been herein assessed.

PMID- 27892569
TI  - An ab initio study of the ground and excited electronic states of the methyl
      radical.
AB  - The ground and some excited electronic states of the methyl radical have been
      characterized by means of highly correlated ab intio techniques. The specific
      excited states investigated are those involved in the dissociation of the
      radical, namely the 3s and 3pz Rydberg states, and the A1 and B1 valence states
      crossing them, respectively. The C-H dissociative coordinate and the HCH bending
      angle were considered in order to generate the first two-dimensional ab initio
      representation of the potential surfaces of the above electronic states of CH3,
      along with the nonadiabatic couplings between them. Spectroscopic constants and
      frequencies calculated for the ground and bound excited states agree well with
      most of the available experimental data. Implications of the shape of the excited
      potential surfaces and couplings for the dissociation pathways of CH3 are
      discussed in the light of recent experimental results for dissociation from low
      lying vibrational states of CH3. Based on the ab initio data some predictions are
      made regarding methyl photodissociation from higher initial vibrational states.

PMID- 27892570
TI  - ortho-Heterofluorene perylenediimides: synthesis, photophysical, and exciton
      dynamic properties.
AB  - Previous studies suggest the perylenediimide (PDI) triplet excited state (T1)
      have been accessible only through bimolecular sensitization, the internal heavy
      atom effect or a sophisticated cascade of nonradiative processes. Here, we
      designed heavy-atom-free PDIs to prompt the Tn <- S1 intersystem crossing (ISC)
      by introducing electron donating heterofluorene groups at the head positions of
      the electron-deficient PDI core. We obtained relatively high ISC efficiency up to
      92% yield. Furthermore, promptly generated PDI triplets can sensitize the
      molecular oxygen quantitatively to yield 1O2, with singlet oxygen generation
      efficiencies (PhiDelta) near to unity. These results further suggest that the ISC
      process of PDIs can be enhanced through the intramolecular charge transfer (ICT)
      interaction, providing guidelines for developing triplet-generating PDIs and
      related rylene diimides for optoelectronic applications.

PMID- 27892571
TI  - The reaction fragility spectrum.
AB  - We report an original method that provides a new insight into the reaction
      mechanism by direct observation of bond breaking and formation. Variations of the
      diagonal elements of the Hessian along the IRC are shown to reflect the
      anharmonic properties of the system that are induced by electron density
      modifications upon the reaction. This information is presented in the form of the
      reaction spectrum, demonstrating how particular atoms engage in the
      reorganization of bonds. The test reactions are: HCOF synthesis and HONS
      isomerization.

PMID- 27892572
TI  - Time-resolved photoelectron imaging of iodide-nitromethane (I-.CH3NO2)
      photodissociation dynamics.
AB  - Femtosecond time-resolved photoelectron spectroscopy is used to probe the decay
      channels of iodide-nitromethane (I-.CH3NO2) binary clusters photoexcited at 3.56
      eV, near the vertical detachment energy (VDE) of the cluster. The production of I
      is observed, and its photoelectron signal exhibits a mono-exponential rise time
      of 21 +/- 1 ps. Previous work has shown that excitation near the VDE of the I
      .CH3NO2 complex transfers an electron from iodide to form a dipole-bound state of
      CH3NO2- that rapidly converts to a valence bound (VB) anion. The long appearance
      time for the I- fragment suggests that the VB anion decays by back transfer of
      the excess electron to iodide, reforming the I-.CH3NO2 anion and resulting in
      evaporation of iodide. Comparison of the measured lifetime to that predicted by
      RRKM theory suggests that the dissociation rate is limited by intramolecular
      vibrational energy redistribution in the re-formed anion between the high
      frequency CH3NO2 vibrational modes and the much lower frequency intermolecular I
      .CH3NO2 stretch and bends, the predominant modes involved in cluster dissociation
      to form I-. Evidence for a weak channel identified as HI + CH2NO2- is also
      observed.

PMID- 27892573
TI  - Thermodynamics of DNA: sensitizer recognition. Characterizing binding motifs with
      all-atom simulations.
AB  - We report the investigation of the thermochemical properties of benzophenone
      interacting with B-DNA studied by all-atom molecular dynamic simulations. In
      particular, we determine the binding free energy for two competitive binding
      modes, minor groove binding and double insertion. Our results allow us to
      quantitatively resolve for the first time the mode of binding of this
      paradigmatic photosensitizer, indicating a marked preference for minor groove
      binding. Furthermore, we have settled a protocol allowing for the determination
      of binding energies in the case of non-covalent interaction with DNA, in
      particular, tackling the non-trivial problem of the strong reorganization of the
      DNA imposing extended statistical sampling. Our contribution paves the way to the
      systematic determination of the thermochemical properties of drugs or pollutants
      interacting with DNA.

PMID- 27892574
TI  - Study of the interplay between N-graphene defects and small Pd clusters for
      enhanced hydrogen storage via a spill-over mechanism.
AB  - The hydrogen spill-over mechanism was studied by applying Density Functional
      Theory. We used small palladium clusters to act as the catalyst supported on the
      substrate (comprised of pyridinic and pyrrolic nitrogen doped graphene), in order
      to study hydrogen dissociation, migration and diffusion. Charge transfer and
      strong binding between the catalyst and the substrate lead to dissociated states
      of H2 and prevent clusters from detaching and coalescing. In dissociated cases of
      H2 on Pd clusters, energy barriers below 0.6 eV were found. Likewise, concerning
      hydrogen migration from the catalyst to the substrate, energy barrier values of
      0.8 eV (pyridinic defect) and 0.5 eV (pyrrolic defect) were apparent in the case
      of the Pd4 cluster at full hydrogen saturation. This indicates that hydrogen
      dissociation and migration may occur spontaneously at room temperature. This
      result shows that the interaction between the defects and the small metal
      clusters may explain the role that defects play in hydrogen migration from the
      catalyst to the substrate. Subsequently, it was found that thermal desorption
      does not limit chemisorbed hydrogen diffusion on the substrate. This work may
      thus help to determine experimental strategies with the capacity to enhance
      hydrogen storage.

PMID- 27892576
TI  - The magnetization orientation of Fe ultrathin layers in contact with graphene.
AB  - In this paper, we study the magnetic and chemical properties of Fe/graphene
      vertically stacked ultrathin films by means of X-ray magnetic circular dichroism
      and X-ray photoelectron spectroscopy. We compare two systems: an iron layer
      deposited directly on top of the Pt(111) surface, and an intercalated Fe film
      sandwiched between graphene and Pt(111). The system composed of a submonolayer Fe
      deposited directly on Pt(111) maintains an out-of-plane easy magnetization axis,
      even if it has been covered by graphene that quenches effectively the magnetic
      orbital moment of Fe. However, when the Fe coverage is increased above 1 ML the
      easy magnetization axis flips in the in-plane direction.

PMID- 27892575
TI  - Heat treated carbon supported iron(ii)phthalocyanine oxygen reduction catalysts:
      elucidation of the structure-activity relationship using X-ray absorption
      spectroscopy.
AB  - This paper focuses on studying the influence of the heat treatment on the
      structure and activity of carbon supported Fe(ii)phthalocyanine (FePc/C) oxygen
      reduction reaction (ORR) catalysts under alkaline conditions. The FePc macrocycle
      was deposited onto ketjen black carbon and heated treated for 2 hours under inert
      atmosphere (Ar) at different temperatures (400, 500, 600, 700, 800, 900 and 1000 
      degrees C). The atomic structure of Fe in each sample has been determined by XAS
      and correlated to the activity and ORR mechanisms determined in electrochemical
      half cells and in a complete H2/O2 anion exchange membrane fuel cells (AEM-FC).
      The results show that the samples prepared at 600 and 700  degrees C have the
      highest electrochemical catalytic activity for the ORR, consistent with the
      findings that the FeN4 active sites are thermally stable up to 700  degrees C,
      confirmed by both XANES linear combination fittings and EXAFS fittings. Upon
      annealing at temperatures above 800  degrees C, the FeN4 structure partially
      decomposes to small iron nanoparticles. The transition from the FeN4 structure to
      metallic Fe results in a significant loss in ORR activity and an increase in the
      production of undesirable HO2- during catalysis.

PMID- 27892577
TI  - Light-soaking effects and capacitance profiling in Cu(In,Ga)Se2 thin-film solar
      cells with chemical-bath-deposited ZnS buffer layers.
AB  - We fabricated Cu(In,Ga)Se2 (CIGS) solar cells with chemical-bath deposited (CBD)
      ZnS buffer layers with different deposition times. The conversion efficiency and
      the fill factor of the CIGS solar cells reveal a strong dependence on the
      deposition time of CBD-ZnS films. In order to understand the detailed
      relationship between the heterojunction structure and the electronic properties
      of CIGS solar cells with different deposition times of CBD-ZnS films, capacitance
      voltage (C-V) profiling measurements with additional laser illumination were
      performed. The light-soaking effects on CIGS solar cells with a CBD-ZnS buffer
      layer were investigated in detail using current density-voltage (J-V) and C-V
      measurements with several different lasers with different emission wavelengths.
      After light-soaking, the conversion efficiency changed significantly and the
      double diode feature in J-V curves disappeared. We explain that the major reason
      for the improvement of efficiency by light-soaking is due to the fact that
      negatively charged and highly defective vacancies in the CIGS absorber near the
      interface of CBD-ZnS/CIGS were formed and became neutral due to carriers
      generated by ultra-violet absorption in the buffer layer.

PMID- 27892578
TI  - A metastable cubic phase of sodium niobate nanoparticles stabilized by chemically
      bonded solvent molecules.
AB  - Structural modification, especially the stabilization of metastable phases at
      room temperature, has emerged as an effective strategy to understand their
      stabilization mechanism and improve their functional properties. In this work, a
      facile solvothermal approach is developed to synthesize metastable sodium niobate
      (NaNbO3) crystals with the cubic symmetry. XRD, Raman and TEM results all
      confirmed the selective synthesis of cubic and orthorhombic NaNbO3via adjustment
      of the reaction medium. The fact that traditional hydrothermal synthesis often
      yields orthorhombic NaNbO3 inspires us to elucidate the formation mechanism of
      cubic NaNbO3 with respect to the solvent effect. With the increasing post
      calcination temperature, the as-synthesized cubic NaNbO3 gradually transforms
      into the orthorhombic structure, which is understood to be a recrystallization
      behavior, as evidenced by the XRD and TEM results. The organic molecules retained
      in the NaNbO3 nanocrystals, as suggested by UV-vis, FT-IR and TGA-MS results,
      have contributed to the stabilization of the metastable structure, demonstrated
      by the different temperature-induced phase transition behaviors in air and argon
      atmospheres, where the phase transition from cubic to orthorhombic would take
      place at a relatively higher temperature in argon. This work provides an
      alternative approach to synthesize cubic NaNbO3 nanocrystals, and the
      understanding of the stabilization mechanism could pave a new pathway for
      fabricating metastable materials.

PMID- 27892579
TI  - Rationalizing fluorescence quenching in meso-BODIPY dyes.
AB  - meso-Substituted boron-dipyrromethene (BODIPY) dyes are a puzzling class of
      molecules, which feature contrasting emissive behaviors. The full mechanistic
      picture for these distinctive properties is still missing. Using static and
      dynamic excited state computations we unravel the key reasons behind these
      divergences.

PMID- 27892580
TI  - Ionic complex of a rhodamine dye with aggregation-induced emission properties.
AB  - An AIE-active rhodamine based luminogen was prepared via a complexation reaction
      between non-emissive rhodamine hydrazide (RdH) and bulky camphorsulfonic acid
      (CSA). Besides acting to open the spirolactam ring of RdH, CSA also imposes a
      rotational restriction on the resultant ionic complex, RdH(CSA)x. Without CSA,
      the analogous complex RdH(HCl)3 is a luminogen with aggregation-caused quenching
      (ACQ) properties. The ionic bonds of RdH(CSA)3 are sensitive to several external
      stimuli and therefore it is a luminescent sensor for metal ions, organic amines
      and the blood protein bovine serum albumin (BSA). Besides being a sensor for BSA,
      the ionic RdH(CSA)3 is also a denaturant capable of uncoiling the peptide chain
      of BSA.

PMID- 27892581
TI  - Tuning of azine derivatives for selective recognition of Ag+ with the in vitro
      tracking of endophytic bacteria in rice root tissue.
AB  - Several azine derivatives have been prepared and structurally characterized by
      spectroscopic and single-crystal X-ray diffraction analysis. Two of them, viz.
      naphthalene based (A10) and anthracene based (A11) show fluorescence enhancement
      in the presence of Ag+ in aqueous-methanol. Moreover, A11 efficiently tracks
      Ag+in vitro endophytic bacteria infected rice root tissue. Experimental results
      have been substantiated by theoretical DFT calculations.

PMID- 27892582
TI  - Lubrication of chocolate during oral processing.
AB  - The structure of chocolate is drastically transformed during oral processing from
      a composite solid to an oil/water fluid emulsion. Using two commercial dark
      chocolates varying in cocoa solids content, this study develops a method to
      identify the factors that govern lubrication in molten chocolate and saliva's
      contribution to lubrication following oral processing. In addition to chocolate
      and its individual components, simulated boluses (molten chocolate and phosphate
      buffered saline), in vitro boluses (molten chocolate and whole human saliva) and
      ex vivo boluses (chocolate expectorated after chewing till the point of swallow)
      were tested. The results reveal that the lubrication of molten chocolate is
      strongly influenced by the presence of solid sugar particles and cocoa solids.
      The entrainment of particles into the contact zone between the interacting
      surfaces reduces friction such that the maximum friction coefficient measured for
      chocolate boluses is much lower than those for single-phase Newtonian fluids. The
      addition of whole human saliva or a substitute aqueous phase (PBS) to molten
      chocolate dissolves sugar and decreases the viscosity of molten chocolate so that
      thinner films are achieved. However, saliva is more lubricating than PBS, which
      results in lower friction coefficients for chocolate-saliva mixtures when
      compared to chocolate-PBS mixtures. A comparison of ex vivo and in vitro boluses
      also suggests that the quantity of saliva added and uniformity of mixing during
      oral processing affect bolus structure, which leads to differences in measured
      friction. It is hypothesized that inhomogeneous mixing in the mouth introduces
      large air bubbles and regions of non-emulsified fat into the ex vivo boluses,
      which enhance wetting and lubrication.

PMID- 27892583
TI  - Resonant tunneling based graphene quantum dot memristors.
AB  - In this paper, we model two-terminal all graphene quantum dot (GQD) based
      resistor-type memory devices (memristors). The resistive switching is achieved by
      resonant electron tunneling. We show that parallel GQDs can be used to create
      multi-state memory circuits. The number of states can be optimised with
      additional voltage sources, whilst the noise margin for each state can be
      controlled by appropriately choosing the branch resistance. A three-terminal GQD
      device configuration is also studied. The addition of an isolated gate terminal
      can be used to add further or modify the states of the memory device. The
      proposed devices provide a promising route towards volatile memory devices
      utilizing only atomically thin two-dimensional graphene.

PMID- 27892584
TI  - A short history of phototherapy, vitamin D and skin disease.
AB  - The earliest record between sun exposure and skin disease goes back five
      millennia to the ancient Egyptians. The modern scientific era of medical light
      therapy and skin diseases started in 1877 when Downs and Blunt reported that
      exposure to light inhibited fungal growth in test tubes. Continuing research
      generated a growing medical interest in the potential the effects of light to
      treat and cure skin diseases considered as parasitic. This culminated in the
      awarding of the 1903 Nobel Prize in Medicine to Niels Finsen for his pioneering
      work showing that light could successfully treat cutaneous mycobacterium
      tuberculosis (lupus vulgaris), a disfiguring disorder common at the time. Cod
      liver oil was used as a folk remedy to treat rickets prior to 1789 in Manchester,
      UK and sunlight was published as the cure for this disease in 1921. The work by
      Hess and Weinstock in 1925 showed that food irradiated with ultraviolet (UV)
      light prevented rickets in rats, which paved the way for the discovery of vitamin
      D. The range of skin diseases treated by light therapy increased in the following
      years, to the point where a 1932 review by the American Medical Association on
      the use of UV therapy in dermatology listed 34 skin conditions for which UV
      radiation may be useful. This period coincided with the development of sanatoria
      in Europe and North America which used heliotherapy for the treatment of
      tuberculosis. UV therapy and vitamin D continued to be used successfully for the
      treatment of tuberculosis up to the 1950s when it was superseded by more
      effective antibiotics. Modern phototherapy developed in the 1980s with the
      discovery of the action spectrum for psoriasis leading to the development of
      narrow band UVB. Subsequently a biological mechanism by which UV light and
      vitamin D treated tuberculosis was identified in 2006. This involves activation
      of human macrophages via toll-like receptors to upregulate the vitamin D receptor
      gene resulting in induction of the antimicrobial peptide cathelicidin. The role
      of UV light and vitamin D in the treatment of skin diseases is currently an
      active area of research.

PMID- 27892585
TI  - Elemental steps of the thermodynamics of dihydropyrimidine: a new class of
      organic hydride donors.
AB  - 25 Dihydropyrimidine derivatives, a new class of organo-hydrides, were designed
      and synthesized by the Biginelli reaction. For the first time, the thermodynamic
      driving forces of the six elemental steps to obtain a hydride in acetonitrile
      were determined by isothermal titration and electrochemical methods,
      respectively. The effects of molecular structures and substituents on these
      thermodynamic parameters were examined, uncovering some interesting structure
      reactivity relationships. Both the thermodynamic and kinetic studies show that
      the hydride transfer from dihydropyrimidines to 9-phenylxanthylium (PhXn+ClO4-)
      prefers a concerted mechanism.

PMID- 27892586
TI  - Bovine serum albumin coated nanoparticles for in vitro activated fluorescence.
AB  - A fluorophore modified nanoparticle was developed that can only fluoresce when a
      specific environmental parameter interacts with the system. The model system
      consisted of an azide modified bovine serum albumin (azBSA) that had been
      covalently attached to an alkyne modified silicon phthalocyanine (alSiPc)
      derivative through a copper catalyzed azide/alkyne Huisgen cycloaddition (click
      reaction). The azBSA/alSiPc assembly was then clicked to a ca. 67 nm
      poly(propargyl acrylate) (PA) nanoparticle (PA/azBSA/alSiPc). The resulting
      particles did not exhibit any florescence when the alSiPc was excited. Incubating
      the particles at 37  degrees C for 30 min with a proteolytic enzyme (trypsin)
      degraded the linking BSA and resulted in the appearance of florescence that was
      attributed to a "free" silicon phthalocyanine. The PA/azBSA/alSiPc particles were
      incubated with human non-small cell lung cancer cells (A549) and the florescence
      of the initially quenched particles was achieved with cellular uptake.

PMID- 27892587
TI  - Total synthesis and confirmation of the revised structures of jiangrines A, C and
      D.
AB  - Our previous total synthesis of the proposed structures of jiangrines C and D
      shows that the characteristic data of synthetic samples did not match those of
      the natural ones, prompting us to revise their structures. Accordingly, we now
      accomplished the total synthesis of jiangrines A, C and D, which confirms our
      deduction that their molecular skeletons should compose of 2,3-disubstituted
      pyrrole instead of 2,5-disubstituted pyrrole. Our current synthesis features a
      silver-catalyzed [3 + 2] cycloaddition between a terminal alkyne and isocyanide,
      and was completed concisely in only seven linear steps.

PMID- 27892588
TI  - Nanoscale electrochemical characterization of a solid-state electrolyte using a
      manganese-based thin-film probe.
AB  - A Li-Mn-O thin-film electrode probe has been developed via a facile synthesis
      process, which enables nanoscale electrochemical investigation of the solid-state
      electrolyte LiPON. Detailed information of ion transport can be obtained by the
      thin-film probe, rather than the macroscale electrochemical impedance analysis.
      It is clarified from the nanoscale analysis that the charge transfer resistance
      at the Li-Mn-O/LiPON interface dominates the localized impedance, while it can be
      significantly reduced rather than the electrolyte resistance by applying a DC
      bias.

PMID- 27892589
TI  - Intramolecular oxidative deselenization of acylselenoureas: a facile synthesis of
      benzoxazole amides and carbonic anhydrase inhibitors.
AB  - A mild, efficient and one pot procedure to access benzoxazoles using easily
      accessible acylselenoureas as starting materials has been discovered. Mechanistic
      studies revealed a pH dependent intramolecular oxidative deselenization, with
      ring closure due to an intramolecular nucleophilic attack of a phenoxide ion. All
      the benzoxazoles herein reported possessed a primary sulfonamide zinc binding
      group and showed effective inhibitory action on the enzymes, carbonic anhydrases.

PMID- 27892590
TI  - Near-infrared selective dynamic windows controlled by charge transfer impedance
      at the counter electrode.
AB  - Recent developments in the exploitation of transparent conductive oxide
      nanocrystals paved the way to the realization of a new class of electrochemical
      systems capable of selectively shielding the infrared heat loads carried by
      sunlight and prospected the blooming of a key enabling technology to be
      implemented in the next generation of "zero-energy" building envelopes. Here we
      report the fabrication of a set of electrochromic devices embodying an engineered
      nanostructured electrode made by high aspect-ratio tungsten oxide nanorods, which
      allow for selectively and dynamically controlling sunlight transmission over the
      near-infrared to visible range. Varying the intensity of applied voltage makes
      the spectral response of the device change across three different optical
      regimes, namely fully transparent, near-infrared only blocking and both visible
      and near-infrared blocking. It is demonstrated that the degree of reversible
      modulation of the thermal radiation entering the glazing element can approach a
      remarkable 85%, accompanied by only a modest reduction in the luminous
      transmittance.

PMID- 27892591
TI  - Pd-mediated cross-coupling of C-17 lithiated androst-16-en-3-ol - access to
      functionalized arylated steroid derivatives.
AB  - Herein, we report on Pd-mediated cross-coupling of vinyllithium steroids and aryl
      bromides to introduce various substituted aryls at C-17 of steroidal frameworks
      based on the structure of epi-androsterone. Compared to other C-C cross
      couplings, this method turned out to be an easy and competitive access to
      biologically interesting C-17 modified steroids.

PMID- 27892592
TI  - Mechanical properties and current-carrying capacity of Al reinforced with
      graphene/BN nanoribbons: a computational study.
AB  - Record high values of Young's modulus and tensile strength of graphene and BN
      nanoribbons as well as their chemically active edges make them promising
      candidates for serving as fillers in metal-based composite materials. Herein,
      using ab initio and analytical potential calculations we carry out a systematic
      study of the mechanical properties of nanocomposites constructed by reinforcing
      an Al matrix with BN and graphene nanoribbons. We consider a simple case of
      uniform distribution of nanoribbons in an Al matrix under the assumption that
      such configuration will lead to the maximum enhancement of mechanical
      characteristics. We estimate the bonding energy and the interfacial critical
      shear stress at the ribbon/metal interface as functions of ribbon width and show
      that the introduction of nanoribbons into the metal leads to a substantial
      increase in the mechanical characteristics of the composite material, as strong
      covalent bonding between the ribbon edges and Al matrix provides efficient load
      transfer from the metal to the ribbons. Using the obtained data, we apply the
      rule of mixtures in order to analytically assess the relationship between the
      composite strength and concentration of nanoribbons. Finally, we study carbon
      chains, which can be referred to as the ultimately narrow ribbons, and find that
      they are not the best fillers due to their weak interaction with the Al matrix.
      Simulations of the electronic transport properties of the composites with
      graphene nanoribbons and carbyne chains embedded into Al show that the inclusion
      of the C phase gives rise to deterioration in the current carrying capacity of
      the material, but the drop is relatively small, so that the composite material
      can still transmit current well, if required.

PMID- 27892593
TI  - Dual-mode refractive index and charge sensing to investigate complex surface
      chemistry on nanostructures.
AB  - This work presents a novel dual-mode charge and refractive index sensitive device
      integrated with nanoplasmonic islands, for the first time, on insulator
      semiconductor junctions. The developed nano-metal-insulator semiconductor (nMIS)
      sensor facilitates simultaneous detection of charge and mass changes on the
      nanoislands due to the binding of biomolecules. The charging of the nanoislands
      is traced by using the capacitive field-effect electrolyte-metal-insulator
      semiconductor structure and the refractive index changes are quantified by
      measuring the change in the localized surface plasmon resonances of the
      nanoislands. To demonstrate the performance of our dual-mode sensor we study the
      effect of oxygen plasma on immobilized biomolecules. As a case study biotinylated
      aptamers specific to interleukin 6 (IL-6) were chosen to conduct the immunoassay
      studies. We confirm that the adsorbed aptamers on the nanoislands do not lose
      their functionality after exposure to low energy oxygen plasma (<600 J). This
      finding is critical for the development of 'ready-to-use' microfluidic
      immunoassay platforms (glass-PDMS based) where immobilizing biomolecules on one
      of the substrates is often required prior to the bonding of glass and PDMS. Our
      results also open new opportunities for utilizing plasma to encapsulate
      biomolecules in polymers and hydrogels. More significantly, nMIS sensors can
      readily be adopted for multiplexed and high throughput label free immunoassay
      systems, further driving innovations in biomedical and healthcare research.

PMID- 27892594
TI  - Chloroprocaine 10 mg/ml for low-dose spinal anaesthesia in perianal surgery - a
      randomised dose finding study.
AB  - BACKGROUND: Low-dose spinal anaesthesia is a safe and reliable anaesthesia
      technique in outpatient perianal surgery. Regarding its short duration of action
      and its trend to hyperbaric characteristics, plain chloroprocaine 10 mg/ml seems
      to be ideal to perform low-dose spinal anaesthesia. The aim of this trial was to
      determine the optimal dosage of chloroprocaine for this indication. METHODS:
      Hundred and twenty patients undergoing perianal surgery were enrolled and
      randomly allocated to receive 10, 20 or 30 mg of chloroprocaine 10 mg/ml
      intrathecally. Patients had to sit upright for at least 10 min after injection.
      We measured the expansion of sensory and motor block and the times until voiding,
      walking without assistance and home discharge. RESULTS: The expansion of the
      sensory (P <= 0.0059) and the motor block (P <= 0.0086) gained with increasing
      doses. At a dose of 30 mg the incidence of a profound, clinically relevant motor
      block was significantly higher compared to 10 and 20 mg (P <= 0.0004). In the 10
      mg group two patients suffered from nociceptive pain due to an incomplete block
      and five patients announced discomfort during procedure. Doses of 10 and 20 mg
      led to a significantly earlier discharge compared to 30 mg (P = 0.0003; P =
      0.0406). CONCLUSION: Plain chloroprocaine 10 mg/ml can successfully be used for
      low-dose spinal anaesthesia in perianal outpatient surgery. Regarding the
      unfavourable motor block and later discharge-times in the 30 mg group on the one
      hand and the block-failures in the 10 mg group on the other, 20 mg can be
      recommended as the optimal dose.

PMID- 27892596
TI  - Extracorporeal Membrane Oxygenation Support in Trauma Versus Nontrauma Patients
      with Noninfectious Acute Respiratory Failure.
AB  - The utility of extracorporeal membrane oxygenation (ECMO) in patients with acute
      respiratory distress syndrome (ARDS) of noninfectious origin remains unclear.
      Data on patients with ARDS of noninfectious origin who underwent ECMO were
      reviewed retrospectively. We compared the pre-ECMO characteristics and hospital
      outcomes of patients with traumatic and nontraumatic ARDS. In total, 23 patients
      (trauma, n = 9; nontrauma, n = 14) were included in the study. The mean patient
      age was 42 years, there were three females, and the mean pre-ECMO Simplified
      Acute Physiologic Score (SAPS) II was 60.0 (49.0-71.0). The hemoglobin level was
      lower and the prothrombin time (PT) more prolonged, prior to initiation of ECMO,
      in traumatic compared with nontraumatic ARDS patients. During the first 48 h of
      ECMO support, the coagulation parameters did not differ between the two groups,
      but the platelet counts, PT, and activated partial thromboplastin time indicated
      that coagulopathy was developing in all patients. The hospital and 28-day
      mortality rates were 21.7 and 13.0%, respectively, and serious neurological
      outcomes (cerebral performance category [CPC] of three points or more) developed
      in 26.1% of all patients; however, the extent of such outcomes did not differ
      between traumatic and nontraumatic ARDS patients. Upon multivariate analysis, the
      pre-ECMO SAPS II tended to be associated with composite events (i.e., hospital
      death and/or a CPC of three points or more) (P = 0.051). Additionally, a history
      of hypertension and an elevated pre-ECMO SAPS II were significant risk factors
      for serious neurological outcomes among hospital survivors (n = 18). In
      conclusion, ECMO support can be associated with favorable outcomes in patients
      with ARDS of noninfectious origin, irrespective of whether the ARDS is associated
      with trauma. The pre-ECMO SAPS II and a history of hypertension may be
      independent risk factors for poor outcomes.

PMID- 27892598
TI  - A novel substrate for multisensor hyperspectral imaging.
AB  - The quality of chemical imaging, especially multisensor hyperspectral imaging,
      strongly depends on sample preparation techniques and instrumental infrastructure
      but also on the choice of an appropriate imaging substrate. To optimize the
      combined imaging of Raman microspectroscopy, scanning-electron microscopy and
      energy-dispersive X-ray spectroscopy, a novel substrate was developed based on
      sputtering of highly purified aluminium onto classical microscope slides. The
      novel aluminium substrate overcomes several disadvantages of classical substrates
      like impurities of the substrate material and contamination of the surface as
      well as surface roughness and homogeneity. Therefore, it provides excellent
      conditions for various hyperspectral imaging techniques and enables high-quality
      multisensor hyperspectral chemical imaging at submicron lateral resolutions.

PMID- 27892597
TI  - A multicenter study on anaphylaxis caused by peanut, tree nuts, and seeds in
      children and adolescents.
AB  - Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western
      countries, but no information is available in Korea. To feature clinical
      characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective
      medical record review was performed in 14 university hospitals in Korea (2009
      2013). One hundred and twenty-six cases were identified, with the mean age of 4.9
      years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%,
      respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut
      were 10.50, 8.74, and 4.61 kUA /l, respectively. Among 50 cases managed in the
      emergency department, 52.0% were treated with epinephrine, 66.0% with steroid,
      94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In
      conclusion, WN, PN, and pine nut were the three most common triggers of
      anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low
      levels of sIgE.

PMID- 27892595
TI  - The Rate of Change in Alcohol Misuse Across Adolescence is Heritable.
AB  - BACKGROUND: Alcohol use typically begins during adolescence and escalates into
      young adulthood. This represents an important period for the establishment of
      alcohol use and misuse patterns, which can have psychosocial and medical
      consequences. Although changes in alcohol use during this time have been
      phenotypically characterized, their genetic nature is poorly understood. METHODS:
      Participants of the Avon Longitudinal Study of Parents and Children completed the
      Alcohol Use Disorders Identification Test (AUDIT) 4 times from age 16 to 20. We
      used Mplus to construct a growth model characterizing changes in AUDIT scores
      across time (N = 4,545, where data were available for at least 2 time points).
      The slope of the model was used as the phenotype in a genomewide association
      study (N = 3,380), followed by secondary genetic analyses. RESULTS: No individual
      marker met genomewide significance criteria. Top markers mapped to biologically
      plausible candidate genes. The slope term was moderately heritable (h2SNP = 0.26,
      p = 0.009), and replication attempts using a meta-analysis of independent samples
      provided support for implicated variants at the aggregate level. Nominally
      significant (p < 0.00001) markers mapped to putatively active genomic regions in
      brain tissue more frequently than expected by chance. CONCLUSIONS: These results
      build on prior studies by demonstrating that common genetic variation impacts
      alcohol misuse trajectories. Influential loci map to genes that merit additional
      research, as well as to intergenic regions with regulatory functions in the
      central nervous system. These findings underscore the complex biological nature
      of alcohol misuse across development.

PMID- 27892599
TI  - Forensic Taxonomy of Android Social Apps.
AB  - An Android social app taxonomy incorporating artifacts that are of forensic
      interest will enable users and forensic investigators to identify the personally
      identifiable information (PII) stored by the apps. In this study, 30 popular
      Android social apps were examined. Artifacts of forensic interest (e.g., contacts
      lists, chronology of messages, and timestamp of an added contact) were recovered.
      In addition, images were located, and Facebook token strings used to tie account
      identities and gain access to information entered into Facebook by a user were
      identified. Based on the findings, a two-dimensional taxonomy of the forensic
      artifacts of the social apps is proposed. A comparative summary of existing
      forensic taxonomies of different categories of Android apps, designed to
      facilitate timely collection and analysis of evidentiary materials from Android
      devices, is presented.

PMID- 27892600
TI  - Artificial neural networks and geometric morphometric methods as a means for
      classification: A case-study using teeth from Carcharhinus sp. (Carcharhinidae).
AB  - Over the past few decades, geometric morphometric methods have become
      increasingly popular and powerful tools to describe morphological data while over
      the same period artificial neural networks have had a similar rise in the
      classification of specimens to preconceived groups. However, there has been
      little research into how well these two systems operate together, particularly in
      comparison to preexisting techniques. In this study, geometric morphometric data
      and multilayer perceptrons, a style of artificial neural network, were used to
      classify shark teeth from the genus Carcharhinus to species. Three datasets of
      varying size and species differences were used. We compared the performance of
      this combination with geometric morphometric data in a linear discriminate
      function analysis, linear measurements in a linear discriminate function
      analysis, and a preexisting methodology from the literature that incorporates
      linear measurements and a two-layered discriminate function analysis. Across
      datasets, geometric morphometric data in a multilayer perceptron tended to yield
      modest accuracies but accuracies that varied less across species whereas other
      methods were able to achieve higher accuracies in some species at the expense of
      lower accuracies in others. Further, the performance of the two-layered
      discriminate function analysis illustrates that constraining what material is
      classified can increase the accuracy of a method. Based on this tradeoff, the
      best methodology will then depend on the scope of the study and the amount of
      material available. J. Morphol. 278:131-141, 2017. (c)(c) 2016 Wiley
      Periodicals,Inc.

PMID- 27892601
TI  - A View to the Future: A Novel Approach for 3D-3D Superimposition and
      Quantification of Differences for Identification from Next-Generation Video
      Surveillance Systems.
AB  - Techniques of 2D-3D superimposition are widely used in cases of personal
      identification from video surveillance systems. However, the progressive
      improvement of 3D image acquisition technology will enable operators to perform
      also 3D-3D facial superimposition. This study aims at analyzing the possible
      applications of 3D-3D superimposition to personal identification, although from a
      theoretical point of view. Twenty subjects underwent a facial 3D scan by
      stereophotogrammetry twice at different time periods. Scans were superimposed two
      by two according to nine landmarks, and root-mean-square (RMS) value of point-to
      point distances was calculated. When the two superimposed models belonged to the
      same individual, RMS value was 2.10 mm, while it was 4.47 mm in mismatches with a
      statistically significant difference (p < 0.0001). This experiment shows the
      potential of 3D-3D superimposition: Further studies are needed to ascertain
      technical limits which may occur in practice and to improve methods useful in the
      forensic practice.

PMID- 27892602
TI  - The Analog Blanking Period of Implantable Cardiac Rhythm Devices.
AB  - BACKGROUND: Analog blanking periods (BPs) that hold down the display of
      electrograms (EGMs) in cardiac rhythm devices have received much less attention
      than the well-known digital BPs which do not influence the EGM display. In
      Biotronik devices (Biotronik GmbH, Berlin, Germany), when a paced event initiates
      an analog BP in one chamber (right atrium, right ventricle [RV], or left
      ventricle [LV]), an identical cross-chamber analog BP starts in the other two
      chambers. METHODS: All clinical observations were recorded from patients with
      Biotronik devices. The effect of the atrial cross-chamber analog BP initiated by
      a ventricular paced event on the atrial EGM was studied in the records of seven
      patients with frequent paroxysmal atrial flutter to determine the effect of
      critically timed RV paced event (RVp) or LV paced event (LVp) upon the atrial
      EGM. The effect of atrial pacing triggering cross-chamber analog BPs in the RV
      and LV channels on the RV and LV EGMs was also investigated in cases of conducted
      supraventricular beats and ventricular premature complexes. The effect of a
      triggered LVp initiating a cross-chamber analog BP in the RV channel on the EGM
      of a sensed RV sensed event was evaluated in 10 cases. Simulation studies were
      also performed to verify the clinical observations. RESULTS: Patients with atrial
      flutter showed intermittent truncation or deformity and even disappearance of the
      atrial signals due to an atrial cross-chamber analog BP initiated by RVp and/or
      LVp. Three patients demonstrated deformity of the signal shape of ventricular
      premature beats falling within a ventricular cross-chamber analog BP initiated by
      right atrial paced event (RAp). We found only one case of a supraventricular QRS
      complex trapped in a ventricular cross-chamber analog BP initiated by RAp. All
      the recordings of LVp triggering upon RVs revealed a variety of RV signal
      deformities occasionally with preservation of the terminal part of the RV signal.
      Simulation studies confirmed the effect of the analog BP on the atrial and the
      ventricular EGMs. CONCLUSION: The analog BP of Biotronik devices may cause
      truncation or deformity of atrial and ventricular signals and the occasional
      disappearance of an atrial signal during atrial flutter. These effects must not
      be interpreted as device malfunction. In the clinical evaluation of the EGM
      curves, the effects of the analog BPs have to be carefully considered in order to
      avoid possible misinterpretation.

PMID- 27892603
TI  - Bone marrow-derived mesenchymal stem cells prevent alopecia areata development
      through the inhibition of NKG2D expression: A pilot study.

PMID- 27892605
TI  - EMILIN3, an extracellular matrix molecule with restricted distribution in skin.
AB  - EMILIN3 is an extracellular matrix glycoprotein that displays a dynamic and
      restricted expression pattern in connective tissues during post-natal life. In
      this study, we report the characterization of EMILIN3 deposition in the skin. In
      addition, to unravel the functions of this protein in skin homeostasis, we
      generated Emilin3 null mice and provide evidence that EMILIN3 is dispensable for
      hair follicle growth and maintenance throughout adult life.

PMID- 27892604
TI  - Interleukin (IL)-6 modulates transforming growth factor-beta receptor I and II
      (TGF-betaRI and II) function in epidermal keratinocytes.
AB  - It been shown that IL-6 modulates TGF-beta1 expression in fibroblasts, however,
      what role IL-6 plays concerning TGF-betaR expression and function in skin is
      unknown. Therefore, the aim of this study was to investigate the mechanism by
      which IL-6 might modulates TGF-beta receptors in skin. Skin from WT, IL-6 over
      expressing mice and IL-6 treated keratinocyte cultures was analysed for TGF
      betaRI and TGF-betaRII expression via histology, PCR and flow cytometry. Receptor
      function was assessed by cell migration, bromodeoxyuridine (BrdU) proliferation
      assays, and Smad7 expression and Smad2/3 phosphorylation. Receptor localization
      within the membrane was determined by co-immunoprecipitation. IL-6 overexpression
      and treatment increased TGF-betaRII expression in the epidermis. IL-6 treatment
      of keratinocytes induced TGF-betaRI and II expression and augmented TGF-beta1
      induced function as demonstrated through increased migration and decreased
      proliferation. Additionally, IL-6 treatment of keratinocytes altered receptor
      activity as indicated by altered Smad2/3 phosphorylation and increased Smad7 and
      membrane localization. These results suggest that IL-6 regulates keratinocyte
      function by modulating TGF-betaRI and II expression and signal transduction via
      trafficking of the receptor to lipid raft pools.

PMID- 27892607
TI  - Hypothalamic alpha-synuclein and its relation to weight loss and autonomic
      symptoms in Parkinson's disease.

PMID- 27892608
TI  - An advanced mouse model for human skin wound healing.
AB  - Here, we report a model for studying wound repair based on skin regenerated from
      human tissue culture-expanded cells. The reconstituted skin (hRSK) responds to
      injury similar to that of intact human skin, and its constituent cells contribute
      to the healing process. As we have demonstrated that hRSK composed of GFP
      labelled cells also heals "normally," we believe this model will be useful in
      analysing the wound repair process using genetically modified human cells.

PMID- 27892609
TI  - Bad air gets under your skin.
AB  - Air pollution is increasing beyond previous estimates and is viewed as the
      world's largest environmental health risk factor. Numerous clinical and
      epidemiological studies have highlighted the adverse effects of environmental
      pollutants on health. Although there is comparatively less research investigating
      the cutaneous effects of ambient pollution, there is growing recognition of the
      adverse effects on skin. In this article, we provide an overview of the nature of
      environmental pollution and highlight the current evidence detailing the effects
      on cutaneous health. There is convincing evidence demonstrating that air
      pollution has a detrimental impact on skin and can exacerbate skin disease.
      Further epidemiological and experimental studies are required to assess the short
      and long-term deleterious effects of ambient pollutant exposure on skin. The
      future challenge would be to use this evidence to develop specific strategies to
      protect against pollution-induced damage and prevent the effects of "bad air
      getting under our skin."

PMID- 27892606
TI  - SVEP1 plays a crucial role in epidermal differentiation.
AB  - SVEP1 is a recently identified multidomain cell adhesion protein, homologous to
      the mouse polydom protein, which has been shown to mediate cell-cell adhesion in
      an integrin-dependent manner in osteogenic cells. In this study, we characterized
      SVEP1 function in the epidermis. SVEP1 was found by qRT-PCR to be ubiquitously
      expressed in human tissues, including the skin. Confocal microscopy revealed that
      SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal
      epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes
      resulted in decreased expression of major epidermal differentiation markers.
      Similarly, SVEP1 downregulation was associated with disturbed differentiation and
      marked epidermal acanthosis in three-dimensional skin equivalents. In contrast,
      the dispase assay failed to demonstrate significant differences in adhesion
      between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1
      knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for
      normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos
      with a Svep1-specific splice morpholino. Scanning electron microscopy revealed a
      rugged epidermis with perturbed microridge formation in the centre of the
      keratinocytes of morphant larvae. Transmission electron microscopy analysis
      demonstrated abnormal epidermal cell-cell adhesion with disadhesion between cells
      in Svep1-deficient morphant larvae compared to controls. In summary, our results
      indicate that SVEP1 plays a critical role during epidermal differentiation.

PMID- 27892611
TI  - Towards a bacterial treatment for armpit malodour.
AB  - Axillary malodour is a frustrating condition for many people. It can lead to
      significant discomforts and various psychological effects. The underarm
      microbiome plays a major role in axillary malodour formation. Not only the
      bacteria on the epidermis, but also and especially those living in the sweat
      glands, sweat pores and hair follicles play a pivotal role in malodour
      development. To treat underarm malodour, this viewpoint article envisions a
      bacterial treatment. Replacing the autochthonous malodour-causing microbiome with
      a non-odour-causing microbiome, through an armpit bacterial transplantation or
      direct application of probiotics/non-odour-causing bacteria, could resolve the
      condition. Selective steering of the microbiome with prebiotics, biochemicals or
      plant extracts can likewise greatly help in improving the underarm odour.
      Elimination/inhibition of the "bad bugs" and application/stimulation of the "good
      bugs" will be part of the future treatment for axillary body odour.

PMID- 27892610
TI  - JAK inhibitor ruxolitinib inhibits the expression of cytokines characteristic of
      cutaneous lupus erythematosus.
AB  - This study was stimulated by the clinical observation of a rapid response of a
      chilblain lupus patient to treatment with JAK1/2-kinase inhibitor ruxolitinib. We
      investigated the in vivo expression of phospho-JAK2 in CLE skin samples as well
      as the immunomodulatory in vitro effect of ruxolitinib in cultured immortalized
      keratinocytes and in a 3D human epidermis model (epiCS). Our results demonstrate
      that ruxolitinib significantly decreases the production of CLE-typical cytokines
      (CXCL10, CXCL9, MxA) and might be a promising drug for future clinical studies in
      patients with CLE and related autoimmune skin diseases.

PMID- 27892612
TI  - The prevalence of depressive symptoms among older patients with hypertension in
      rural China.
AB  - OBJECTIVE: The comorbidity of depression and hypertension (HTN) is common and
      complicates the management of both conditions. This study investigated the
      prevalence of depressive symptoms among older patients with HTN in rural China
      and explored the relationship between the two conditions. METHODS: The baseline
      data of older patients diagnosed with HTN included in the depression/HTN in
      Chinese Older Adults-Collaborations for Health Study were used for the analysis.
      The Chinese Older Adults-Collaborations for Health Study was conducted in rural
      villages of Tonglu County, Zhejiang Province, China. In all, 10 389 older village
      residents had HTN (57.2% female, mean age 71.5 +/- 8.1 years). Blood pressure was
      measured by using a calibrated manual sphygmomanometer and stethoscope.
      Depressive symptom was measured by using the Chinese version of the nine-item
      Patient Health Questionnaire. RESULTS: Among 10 389 patients with HTN, 12.8% had
      significant depressive symptoms (nine-item Patient Health Questionnaire >= 10).
      Rates of significant depressive symptoms were 5.3% and 32.8% among patients with
      controlled and uncontrolled HTN (systolic blood pressure >= 140 and/or diastolic
      blood pressure >= 90), respectively (chi2  = 8.701, p < 0.001). Logistic
      regression analysis indicated that those in older age group (>=70 years) and with
      uncontrolled HTN have higher rates of significant depressive symptoms than those
      who are younger (age 60 to <70) and with controlled HTN. CONCLUSION: Our findings
      show high rates of depressive symptoms among patients with HTN in rural China and
      higher rates of depressive symptoms among patients with uncontrolled HTN. These
      support the development and dissemination of integrative care approaches for
      older adults with HTN and depression in rural China. Copyright (c) 2016 John
      Wiley & Sons, Ltd.

PMID- 27892613
TI  - Depressive symptoms, prediabetes, and incident diabetes in older English adults.
AB  - OBJECTIVE: The objective of this study was to assess the risk of diabetes in
      older adults with elevated depressive symptoms, prediabetes, or both. METHOD:
      This study included 4129 participants from the English Longitudinal Study of
      Ageing. Participants were followed from Wave 2 (2004-2005) to Wave 6 (2012-2013).
      The 8-item Centre for Epidemiologic Studies Depression (CESD) scale was used to
      measure depressive symptoms in the past week, which were categorized as no/low,
      mild, or high. Normal glucose levels and prediabetes were defined using baseline
      haemoglobin A1c measurements. Incident diagnosed diabetes was reported by
      participants. Cox regression estimated hazard ratios of incident diabetes
      associated with depressive symptoms and prediabetes. RESULTS: A total of 157
      participants were diagnosed with diabetes over a mean of 6.7 years. Relative to
      participants with normal glucose levels and no/low depressive symptoms at
      baseline, the adjusted hazard ratios were 0.85 (95% CI 0.40-1.82) and 1.62 (95%
      CI 0.84-3.15) for those with normal glucose levels and mild depressive symptoms
      and normal glucose levels and high depressive symptoms. The adjusted hazard
      ratios for participants with prediabetes and no/low depressive symptoms, mild
      depressive symptoms, and high depressive symptoms were 4.84 (95% CI 3.08-7.60),
      7.17 (95% CI 4.00-12.88), and 7.77 (95% CI 4.33-13.93), respectively.
      CONCLUSIONS: Older adults with elevated depressive symptoms and prediabetes have
      an increased risk of diabetes compared to those with only one of these risk
      factors. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27892615
TI  - So you want to publish in International Nursing Review? A few words of advice for
      authors.

PMID- 27892617
TI  - Does education in Italy produce nurses fit for future healthcare needs?

PMID- 27892616
TI  - A policy analysis of teamwork as a proposal for healthcare humanization:
      implications for nursing.
AB  - AIM: To analyse the implications of the political devices of the Brazilian
      National Humanization Policy, Singular Therapeutic Project and Reference Team and
      Matrix Support, for nursing as a professional discipline. BACKGROUND: The
      Brazilian Unified Health System, SUS-Brazil, has as its principles regarding
      health care: universal access at all levels of care; equality and non
      discrimination; integrality; community participation; and political and
      administrative decentralization, regionalization, and hierarchization. The
      National Humanization Policy is a public health policy that serves as the
      methodological apparatus for the application of the SUS-Brazil principles.
      Reference Teams refers to inter- and transdisciplinary/professional teams. These
      team approaches are associated with increased quality of care. METHODS:
      Qualitative lexical content policy analysis of the official documents for the
      Brazilian National Humanization Policy. FINDINGS: The Reference Team model that
      is used to carry out Singular Therapeutic Projects leads to discussion of
      disciplinary boundaries in the context of health care. CONCLUSION AND
      IMPLICATIONS FOR NURSING AND HEALTH POLICY: The Brazilian National Humanization
      Policy demands inclusion of various kinds of knowledge and networking. Research
      is needed to elucidate the nature of nursing care and its distinctive character
      in relation to the work objectives of other professional disciplines.

PMID- 27892614
TI  - Validation of a prognostic index for Huntington's disease.
AB  - BACKGROUND: Characterizing progression in Huntington's disease is important for
      study the natural course and selecting appropriate participants for clinical
      trials. OBJECTIVES: The aim was to develop a prognostic index for motor diagnosis
      in Huntington's disease and examine its predictive performance in external
      observational studies. METHODS: The prediagnosis Neuro-biological Predictors of
      Huntington's Disease study (N = 945 gene-positive) was used to select a Cox
      regression model for computing a prognostic index. Cross-validation was used for
      selecting a model with good internal validity performance using the research
      sites as natural splits of the data set. Then, the external predictive
      performance was assessed using prediagnosis data from three additional
      observational studies, The Cooperative Huntington Observational Research Trial (N
      = 358), TRACK-HD (N = 118), and REGISTRY (N = 480). RESULTS: Model selection
      yielded a prognostic index computed as the weighted combination of the UHDRS
      total motor score, Symbol Digit Modalities Test, baseline age, and cytosine
      adenine-guanine expansion. External predictive performance was very good for the
      first two of the three studies, with the third being a much more progressed
      cohort than the other studies. The databases were pooled and a final Cox
      regression model was estimated. The regression coefficients were scaled to
      produce the prognostic index for Huntington's disease, and a normed version,
      which is scaled relative to a 10-year 50% probability of motor diagnosis.
      CONCLUSION: The positive results of this comprehensive validity analysis provide
      evidence that the prognostic index is generally useful for predicting
      Huntington's disease progression in terms of risk of future motor diagnosis. The
      variables for the index are routinely collected in ongoing observational studies
      and the index can be used to identify cohorts for clinical trial recruitment. (c)
      2016 International Parkinson and Movement Disorder Society.

PMID- 27892619
TI  - Investing in the health workforce-keeping up the momentum.

PMID- 27892620
TI  - Building a National Surveillance System for Malpractice Claims.

PMID- 27892621
TI  - CANDOR: The Antidote to Deny and Defend?

PMID- 27892622
TI  - Changes in Physician Practice Patterns after Implementation of a Communication
      and-Resolution Program.
AB  - OBJECTIVE: To test if a 2006 communication-and-resolution program to address
      unexpected adverse outcomes was associated with changes in cost and use
      trajectories. DATA SOURCE: Records of patients discharged with a principal
      diagnosis of chest pain from 44 nonfederal general hospitals in Cook County,
      Illinois, between January 2002 and December 2009. STUDY DESIGN: Propensity-score
      matched discharges from the intervention and comparison hospitals before
      computing difference-in-differences estimates of quarterly growth rates. DATA
      COLLECTION METHODS: We used discharge records submitted to a central statewide
      repository. PRINCIPAL FINDINGS: Relative to the comparison hospitals and to pre
      implementation trends, and consistent with reduced testing at presentation, the
      intervention hospital recorded an increase in the number of patients with a
      principal diagnosis of chest pain. Among admitted patients, quarterly growth
      rates of clinical laboratory and radiology charges at the intervention hospital
      declined by 3.8 and 6.9 percentage points. CONCLUSIONS: Among patients with chest
      pain, the implementation of a comprehensive communication-and-resolution program
      was associated with substantially reduced growth rates in the use of diagnostic
      testing and imaging services. Further research is needed to establish to what
      extent these changes were attributable to the program and clinically appropriate.

PMID- 27892623
TI  - Addressing Ambulatory Safety and Malpractice: The Massachusetts PROMISES Project.

PMID- 27892624
TI  - Paving the Way for Progress: The Agency for Healthcare Research and Quality
      Patient Safety and Medical Liability Demonstration Initiative.

PMID- 27892625
TI  - Progress at the Intersection of Patient Safety and Medical Liability: Insights
      from the AHRQ Patient Safety and Medical Liability Demonstration Program.
AB  - OBJECTIVE: To identify lessons learned from the experience of the Agency for
      Healthcare Research and Quality (AHRQ) Patient Safety and Medical Liability
      (PSML) Demonstration Program. DATA SOURCES/STUDY SETTING: On September 9, 2009,
      President Obama directed the Secretary of Health and Human Services to authorize
      demonstration projects that put "patient safety first" with the intent of
      reducing preventable adverse outcomes and stemming liability costs. Seven
      demonstration projects received 3 years of funding from AHRQ in the summer of
      2010, and the program formally came to a close in June 2015. STUDY DESIGN: The
      seven grantees implemented complex, broad-ranging innovations addressing both
      patient safety and medical liability in "real-world" contexts. Some projects
      featured novel approaches, while others implemented adaptations of existing
      models. Each project was funded by AHRQ to collect data on the impact of its
      interventions. In addition, AHRQ funded a cross-cutting qualitative evaluation
      focused on lessons learned in implementing PSML interventions. DATA
      COLLECTION/EXTRACTION METHODS: Site visits and follow-up interviews supplemented
      with material abstracted from formal project reports to AHRQ. PRINCIPAL FINDINGS:
      The PSML demonstration projects focused on three broad approaches: (1) improving
      communication around adverse events through disclosure and resolution programs;
      (2) preventing harm through implementation of clinical "best practices"; and (3)
      exploring alternative methods of settling claims. Although the demonstration
      contributed to accumulating evidence that these kinds of interventions can
      positively affect outcomes, there is also evidence to suggest that these
      interventions can be difficult to scale. CONCLUSIONS: In addition to producing at
      least preliminary positive outcomes, the demonstration also lends credence to the
      idea that targeted interventions that improve some aspect of patient safety or
      malpractice performance may also contribute more broadly to institutional culture
      and the alignment of all parties around reducing risk and preventing harm.
      However, more empirical work needs to be carried out to quantify the effect of
      such interventions.

PMID- 27892626
TI  - WITHDRAWN: Root canal posts for the restoration of root filled teeth.
AB  - BACKGROUND: The foundation for the reconstruction of endodontically-treated teeth
      can be provided by a metal or a non-metal post and core system but no guidelines
      exist for choosing one or the other in particular clinical cases. OBJECTIVES: To
      assess the effectiveness of different post and core systems for the restoration
      of endodontically-treated teeth. The primary objective of this review was to
      compare the clinical failure rates of the different types of posts. SEARCH
      METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2005, Issue 3), MEDLINE (from 1966 to September 2005),
      Scopus (from January 1985 to December 2004) and EMBASE (until December 2004). We
      looked through reference lists of articles and dental conference proceedings. We
      contacted researchers in the field and manufacturers. SELECTION CRITERIA:
      Randomised or quasi-randomised clinical trials (RCTs) comparing failures on
      endodontically-treated permanent teeth with different types of post. The outcomes
      were loss of retention, post fracture and root fracture. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed the quality of trials and
      extracted data. Study authors were contacted for additional information. MAIN
      RESULTS: Two trials involving 317 participants were included but only one of
      them, involving 200 participants, compared metal to non-metal posts. The other
      answered to the secondary objective. The risk of failure was greater with metal
      cast posts (9/98) compared to carbon fibre posts (0/97) (risk ratio (RR) = 0.05
      (95% confidence interval (CI) 0.00 to 0.90)) but the study was at high risk of
      bias. Thus fewer failures occurred when using non-metal posts but the evidence is
      unreliable. AUTHORS' CONCLUSIONS: Our systematic review could not specify which
      type of post and core system should be used when two or three dentine walls
      remain. More RCTs are needed to confirm whether fibre-reinforced post and core
      systems are superior and to clarify the influence of the remaining tooth
      structure on the treatment outcome of the different post and core systems
      available. Well-defined inclusion criteria focusing on the number of dentine
      walls (two or three) should be used.

PMID- 27892627
TI  - WITHDRAWN: Pulp management for caries in adults: maintaining pulp vitality.
AB  - BACKGROUND: There is a range of treatment options for the management of the pulp
      in extensively decayed teeth. These include direct and indirect pulp capping,
      pulpotomy or pulpectomy. If the tooth is symptomatic or if there are periapical
      bone changes, then endodontic treatment is required. However, if the tooth is
      asymptomatic but the caries is extensive, there is no consensus as to the best
      method of management. In addition, there has been a recent move towards using
      alternative materials and methods such as the direct or indirect placement of
      bonding agents and mineral trioxide aggregate.Most studies have investigated the
      management of asymptomatic carious teeth with or without an exposed dental pulp
      using various capping materials (e.g. calcium hydroxide, Ledermix, Triodent,
      Biorex, etc.). However, there is no long term data regarding the outcome of
      management of asymptomatic, carious teeth according to different regimens.
      OBJECTIVES: This study aims to assess the effectiveness of techniques used to
      treat asymptomatic carious teeth and maintain pulp vitality. SEARCH METHODS:
      Electronic searches of the following databases were undertaken: The Cochrane Oral
      Health Group's Trials Register (March 2006), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 1), MEDLINE (1966
      to week 4, February 2006), EMBASE (1974 to 13 March 2006), National Research
      Register (March 2006), Science Citation Index - SCISEARCH (1981 to March 2006).
      Detailed search strategies were developed for each database. Handsearching and
      screening of reference lists were undertaken. There was no restriction with
      regard to language of publication. SELECTION CRITERIA: Studies included were
      randomised controlled trials (RCTs). Asymptomatic vital permanent teeth with
      extensive caries were included. Studies were those which compared techniques to
      maintain pulp vitality. Outcome measures included clinical success and adverse
      events. DATA COLLECTION AND ANALYSIS: Data were independently extracted by three
      review authors. Authors were contacted for details of randomisation and
      withdrawals and a quality assessment was carried out. The Cochrane
      Collaboration's statistical guidelines were followed. MAIN RESULTS: Only four
      RCTs were identified. Interventions examined included: Ledermix, glycerrhetinic
      acid/antibiotic mix, zinc oxide eugenol, calcium hydroxide, Cavitec, Life, Dycal,
      potassium nitrate, dimethyl isosorbide, and polycarboxylate cement. Only one
      study showed a statistically significant finding; potassium nitrate/dimethyl
      isosorbide/polycarboxylate cement resulted in fewer clinical symptoms than
      potassium nitrate/polycarboxylate cement or polycarboxylate cement alone when
      used as a capping material for carious pulps. AUTHORS' CONCLUSIONS: It was
      disappointing that there were so few studies which could be considered as being
      suitable for inclusion in this review. The findings from this review do not
      suggest that there should be any significant change from accepted conventional
      practice procedures when the pulp of the carious tooth is considered. Further
      well designed RCTs are needed to investigate the potential of contemporary
      materials which may be suitable when used in the management of carious teeth. It
      is recognised that it is difficult to establish the 'ideal' clinical study when
      ethical approval for new materials must be sought and strict attention to case
      selection, study protocol and interpretation of data is considered. It is also
      not easy to recruit sufficient numbers of patients meeting the necessary
      criteria.

PMID- 27892628
TI  - Association between FOXP3 gene polymorphisms and risk of differentiated thyroid
      cancer in Chinese Han population.
AB  - BACKGROUND: Foxp3 plays important roles in autoimmune and inflammatory diseases
      as well as human malignancies. This study aimed to investigate the association
      between Foxp3 gene polymorphisms and the susceptibility to differentiated thyroid
      cancers (DTC). METHODS: Genotyping was performed by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) in 350 DTC patients and 306
      healthy controls. FOXP3 relative expression was measured by real-time
      quantitative PCR (qRT-PCR). RESULTS: AA/AC genotype of Foxp3-rs3761548 was
      associated with a higher risk of DTC. The frequency of Foxp3-rs2280883 CC/CT
      genotype was lower in DTC patients. Besides, the AA/AC genotype of rs3761548 was
      more frequent in female DTC than male DTC. The association between two single
      nucleotide polymorphisms (SNPs) and clinical characteristics of DTC was further
      analyzed. We found that rs3761548 AA/AC genotype was more frequent in severe DTC
      patients (tumor diameter >1 cm) compared with the relative tender DTC patients
      (tumor diameter <1 cm). On the contrast, the frequency of rs2280883 CC/CT
      genotype was lower in severe DTC patients. In addition, the Foxp3 relative
      expression in DTC with AA/AC genotype of rs3761548 was higher than that of DTC
      with CC genotype. CONCLUSION: Our findings suggested that Foxp3 polymorphisms
      were associated with the risk of DTC in Chinese Han population.

PMID- 27892629
TI  - Identification of novel antimelanogenic hexapeptides via positional scanning of a
      synthetic peptide combinatorial library.

PMID- 27892631
TI  - Flash-Induced Self-Limited Plasmonic Welding of Silver Nanowire Network for
      Transparent Flexible Energy Harvester.
AB  - The outstanding performance (sheet resistance of 5 Omega sq-1 at transmittance of
      90%) and strongly adhesive (30.7 J m-2 ) silver nanowires (AgNWs) are fabricated
      using flash-induced plasmonic welding (FPW) based on theoretical research of
      photothermal interactions. The FPW-processed AgNWs are utilized as electrodes of
      a transparent flexible energy harvester, and this device exhibits excellent
      transmittance and high electric output performance. The FPW methodology provides
      a high-tech solution for transparent flexible electronics.

PMID- 27892630
TI  - Light Triggered Co-Assembly of Photocleavable Copolymers and Polyoxometalates
      with Enhanced Photoluminescence.
AB  - A novel co-assembly based on the block copolymer bearing photocleavable groups
      and macroanionic polyoxometalates Na9 [Ln(W5 O18 )2 ] (LnW10 , Ln = Eu, Dy)
      triggered by UV light is realized in aqueous solution. The copolymer synthesized
      by atom transfer radical polymerization (ATRP) undergoes irreversible cleavage
      upon UV irradiation to generate primary amine (pKa ~ 8-9) residues which are
      completely protonated under a neutral pH in aqueous solution. Electrostatic
      attractions between the resulting positively charged copolymers and anionic LnW10
      drive the formation of assemblies. In situ small angle X-ray scattering and
      transmission electron microscopy are used to characterize the morphology of the
      assemblies. The microenvironments around polyoxometalates in the core of hybrid
      assemblies become highly hydrophobic, resulting in dramatically enhanced
      photoluminescence with the obvious intensity enhancement. The solution parameters
      pH and salt additives show great effects on the formation of assemblies.

PMID- 27892632
TI  - Efficient Cyclometalated Platinum(II) Complex with Superior Operational
      Stability.
AB  - A tetradentate cyclometalated Pt(II) complex (PtN3N) is developed as an
      efficient, stable phosphorescent emitter. One PtN3N device exhibits an estimated
      LT97 of 2057 h at an initial luminance of 1000 cd m-2 , while maintaining an
      external quantum efficiency of 15.3% at such high brightness, demonstrating
      performance to overcome the last technical barrier to the commercialization of Pt
      complexes for many applications.

PMID- 27892634
TI  - Ultrasensitive SERS Detection by Defect Engineering on Single Cu2 O
      Superstructure Particle.
AB  - A Cu2 O superstructure is constructed through a recrystallization-induced self
      assembly strategy. Single Cu2 O superstructure particle exhibits an outstanding
      surface-enhanced Raman spectroscopy performance with the limit of detection as
      low as 10-9 mol L-1 and metal comparable enhancement factor (8 * 105 ) due to the
      synergetic effect of vacancies defect-facilitated charge-transfer process and
      copper vacancies defect-induced electrostatic adsorption.

PMID- 27892633
TI  - Dihydroavenanthramide D inhibits mast cell degranulation and exhibits anti
      inflammatory effects through the activation of neurokinin-1 receptor.
AB  - Chronic pruritus is difficult to treat. Current treatment options are frequently
      ineffective and new therapeutic approaches are urgently needed. Avenanthramides
      are active substances in oats that exhibit anti-inflammatory effects. Their
      potential to interrupt pruritus mechanisms was investigated in this study. It was
      found that the synthetic analog dihydroavenanthramide D (DHAvD) can interact with
      the neurokinin-1 receptor (NK1R) and inhibit mast cell degranulation. DHAvD also
      affects inflammatory processes and reduces secretion of the cytokine interleukin
      6. Our findings indicate that DHAvD may act as a NK1R inhibitor and could be a
      promising candidate for topical treatments of chronic pruritus.

PMID- 27892635
TI  - Electrically Rechargeable Zinc-Air Batteries: Progress, Challenges, and
      Perspectives.
AB  - Zinc-air batteries have attracted much attention and received revived research
      efforts recently due to their high energy density, which makes them a promising
      candidate for emerging mobile and electronic applications. Besides their high
      energy density, they also demonstrate other desirable characteristics, such as
      abundant raw materials, environmental friendliness, safety, and low cost. Here,
      the reaction mechanism of electrically rechargeable zinc-air batteries is
      discussed, different battery configurations are compared, and an in depth
      discussion is offered of the major issues that affect individual cellular
      components, along with respective strategies to alleviate these issues to enhance
      battery performance. Additionally, a section dedicated to battery-testing
      techniques and corresponding recommendations for best practices are included.
      Finally, a general perspective on the current limitations, recent application
      targeted developments, and recommended future research directions to prolong the
      lifespan of electrically rechargeable zinc-air batteries is provided.

PMID- 27892636
TI  - Impaired Retinal Vasoreactivity: An Early Marker of Stroke Risk in Diabetes.
AB  - Diabetes is a common cause of small vessel disease leading to stroke and vascular
      dementia. While the function and structure of large cerebral vessels can be
      easily studied, the brain's microvasculature remains difficult to assess.
      Previous studies have demonstrated that structural changes in the retinal vessel
      architecture predict stroke risk, but these changes occur at late disease stages.
      Our goal was to examine whether retinal vascular status can predict cerebral
      small vessel dysfunction during early stages of diabetes. Retinal vasoreactivity
      and cerebral vascular function were measured in 78 subjects (19 healthy controls,
      22 subjects with prediabetes, and 37 with type-2 diabetes) using a new
      noninvasive retinal imaging device (Dynamic Vessel Analyzer) and transcranial
      Doppler studies, respectively. Cerebral blood vessel responsiveness worsened with
      disease progression of diabetes. Similarly, retinal vascular reactivity was
      significantly attenuated in subjects with prediabetes and diabetes compared to
      healthy controls. Subjects with prediabetes and diabetes with impaired cerebral
      vasoreactivity showed mainly attenuation of the retinal venous flicker response.
      This is the first study to explore the relationship between retinal and cerebral
      vascular function in diabetes. Impairment of venous retinal responsiveness may be
      one of the earliest markers of vascular dysfunction in diabetes possibly
      indicating subsequent risk of stroke and vascular dementia.

PMID- 27892637
TI  - Distribution of follicles in canine ovarian tissues and xenotransplantation of
      cryopreserved ovarian tissues with even distribution of follicles.
AB  - Ovarian follicles are not homogeneously distributed within the ovarian cortex in
      several species of mammals. Yet to maximize the reproducibility of experimental
      results of ovarian transplantation, it is essential to assess the degree of
      density and distribution of follicles in ovarian tissues before their
      transplantation. In this study, the ovarian cortex from 13 immature bitches (ten
      purebred and three mongrels) was sectioned into 1.0- to 1.5-mm3 cubes, those were
      fixed, sectioned and stained with haematoxylin and eosin. To evaluate the density
      and distribution of follicles, the mean number of all stages of follicles per
      square millimetre was calculated after observation under a microscope. The
      distribution of follicles was considered even when the variance value was lower
      than 10 or between 10 and 16, with an absolute value of distortion inferior to 1.
      The mean number of follicles ranged from 3.24 to 28.34/mm2 in 25 ovaries from 13
      bitches examined. The variance and distortion ranged from 0.35 to 119.64 and 
      1.87 to 4.40, respectively. The distribution of follicles within the ovarian
      cortex was judged uneven in 12 of 25 ovaries. These results indicated that
      follicles were not homogeneously distributed within the ovarian cortex in a large
      proportion of ovaries. In addition, cryopreserved ovarian fragments with even
      distribution of follicles were transplanted to NSG mice with or without 400 U/kg
      of disialylated erythropoietin (asialo EPO). After removing both sides of ovary,
      a piece of ovarian fragment was placed under the kidney capsule in both sides of
      kidney. At 4 weeks after transplantation, the fragments were recovered from the
      mice and the number of primordial, primary, secondary and antral follicles was
      counted. Total number of follicles and survival rates of follicles in
      transplanted fragments with asialo EPO were higher than without asialo EPO in
      four bitches examined. These findings suggest that asialo EPO might be effective
      on the follicular survival of canine ovarian tissues after xenotransplantation.
      Knowing the degree of density and distribution of follicles in ovarian tissues
      before transplantation is expected to contribute to the precise interpretation of
      results after transplantation of the ovarian tissues.

PMID- 27892638
TI  - A New Nonfullerene Electron Acceptor with a Ladder Type Backbone for High
      Performance Organic Solar Cells.
AB  - Nonfullerene acceptor FDICTF (2,9-bis(2methylene-(3-(1,1
      dicyanomethylene)indanone))-7,12-dihydro-4,4,7,7,12,12-hexaoctyl-4H
      cyclopenta[2",1":5,6;3",4":5',6']diindeno[1,2-b:1',2'-b']dithiophene) modified by
      fusing the fluorene core in a precursor, yields 10.06% high power conversion
      efficiency, and demonstrates that the ladder and fused core backbone in A-D-A
      structure molecules is an effective design strategy for high-performance
      nonfullerene acceptors.

PMID- 27892640
TI  - Novel topical therapy for corneal blood staining.

PMID- 27892639
TI  - Converting Red Blood Cells to Efficient Microreactors for Blood Detoxification.
AB  - A simple method to convert red blood cells (RBCs) into efficient microreactors is
      reported. Triton X-100 is employed at finely tuned concentrations to render RBCs
      highly permeable to substrates, while low concentrations of glutaraldehyde are
      used to stabilize cells. The ability for blood detoxification of these
      microreactors is demonstrated.

PMID- 27892641
TI  - The Effect of Illustration on Improving Text Comprehension in Dyslexic Adults.
AB  - This study analyses the effect of pictures in reading materials on the viewing
      patterns of dyslexic adults. By analysing viewing patterns using eye-tracking, we
      captured differences in eye movements between young adults with dyslexia and
      controls based on the influence of reading skill as a continuous variable of the
      total sample. Both types of participants were assigned randomly to view either
      text-only or a text + picture stimuli. The results show that the controls made an
      early global overview of the material and (when a picture was present) rapid
      transitions between text and picture. Having text illustrated with a picture
      decreased scores on questions about the learning material among participants with
      dyslexia. Controls spent 1.7% and dyslexic participants 1% of their time on the
      picture. Controls had 24% fewer total fixations; however, 29% more of the control
      group's fixations than the dyslexic group's fixations were on the picture. We
      also looked for effects of different types of pictures. Dyslexic subjects
      exhibited a comparable viewing pattern to controls when scenes were complex, but
      fewer fixations when scenes were neutral/simple. Individual scan paths are
      presented as examples of atypical viewing patterns for individuals with dyslexia
      as compared with controls. (c) 2016 The Authors. Dyslexia published by John Wiley
      & Sons Ltd.

PMID- 27892642
TI  - New approaches to non-surgical sterilization for dogs and cats: Opportunities and
      challenges.
AB  - Over the last 40 years, researchers have explored methods to non-surgically
      suppress fertility in animals. Immunocontraception has been used to control
      wildlife populations but does not confer long-term immunity. The gonadotropin
      releasing hormone (GnRH) agonist deslorelin, formulated as an implant to provide
      6-month to 1-year suppression of fertility in male dogs, is available
      commercially in some countries. Neither of these approaches provide permanent
      sterility. A single-dose, permanent treatment would be a valuable tool in dog and
      cat population control. The Michelson Prize and Grants (MPG) programme was
      initiated "to eliminate shelter euthanasia of healthy, adoptable companion
      animals and reduce populations of feral and free-roaming cats and dogs" offering
      a $25 million US prize for a non-surgical sterilant that is effective as a single
      treatment in both male and female dogs and cats. Michelson Prize and Grants
      programme has offered US $50 million in grant money for research and has
      attracted scientists worldwide. Approaches under study include gene therapy,
      small interfering RNA to inhibit reproductive targets and delivery of cytotoxins
      to pituitary gonadotrophs or GnRH producing neurons in the hypothalamus. Research
      in implant technology that could deliver compounds over an animal's lifetime is
      also underway. Details of funded grants and results to date can be found at:
      http://www.michelsonprizeandgrants.org/michelson-grants/research-findings. The
      next steps are translating the most promising research into products. The
      Alliance for Contraception of Cats and Dogs (ACC&D) is helping to research
      practical methods of marking sterilized animals to avoid costly retreatment and
      population modelling that will help guide field workers in use of resources for
      sterilization programmes.

PMID- 27892644
TI  - Saliva protein biomarkers to detect oral squamous cell carcinoma (OSCC).

PMID- 27892643
TI  - The rice OsNAC6 transcription factor orchestrates multiple molecular mechanisms
      involving root structural adaptions and nicotianamine biosynthesis for drought
      tolerance.
AB  - Drought has a serious impact on agriculture worldwide. A plant's ability to adapt
      to rhizosphere drought stress requires reprogramming of root growth and
      development. Although physiological studies have documented the root adaption for
      tolerance to the drought stress, underlying molecular mechanisms is still
      incomplete, which is essential for crop engineering. Here, we identified OsNAC6
      mediated root structural adaptations, including increased root number and root
      diameter, which enhanced drought tolerance. Multiyear drought field tests
      demonstrated that the grain yield of OsNAC6 root-specific overexpressing
      transgenic rice lines was less affected by drought stress than were nontransgenic
      controls. Genome-wide analyses of loss- and gain-of-function mutants revealed
      that OsNAC6 up-regulates the expression of direct target genes involved in
      membrane modification, nicotianamine (NA) biosynthesis, glutathione relocation,
      3'-phophoadenosine 5'-phosphosulphate accumulation and glycosylation, which
      represent multiple drought tolerance pathways. Moreover, overexpression of
      NICOTIANAMINE SYNTHASE genes, direct targets of OsNAC6, promoted the accumulation
      of the metal chelator NA and, consequently, drought tolerance. Collectively,
      OsNAC6 orchestrates novel molecular drought tolerance mechanisms and has
      potential for the biotechnological development of high-yielding crops under water
      limiting conditions.

PMID- 27892646
TI  - Trafficking of PfExp1 to the parasitophorous vacuolar membrane of Plasmodium
      falciparum is independent of protein folding and the PTEX translocon.
AB  - Having entered the mature human erythrocyte, the malaria parasite survives and
      propagates within a parasitophorous vacuole, a membrane-bound compartment
      separating the parasite from the host cell cytosol. The bounding membrane of this
      vacuole, referred to as the parasitophorous vacuolar membrane (PVM), contains
      parasite-encoded proteins, but how these membrane proteins are trafficked to the
      PVM remains unknown. Here, we have studied the trafficking of PfExp1 to the PVM.
      We find that trafficking of PfExp1 to the PVM is independent of the folding state
      of the protein and also continues unabated upon inactivation of the PVM
      translocon Plasmodium Translocon of Exported proteins (PTEX). Our data strongly
      suggest that the trafficking of membrane proteins to the PVM occurs by as yet
      unknown mechanism, potentially unique to Plasmodium.

PMID- 27892645
TI  - Endothelial cell-derived endothelin-1 is involved in abnormal scar formation by
      dermal fibroblasts through RhoA/Rho-kinase pathway.
AB  - Hypertrophic scars and keloids are characterized by excessive dermal deposition
      of extracellular matrix due to fibroblast-to-myofibroblast differentiation.
      Endothelin-1 (ET-1) is primarily produced by vascular endothelial cells and plays
      multiple roles in the wound-healing response and organ fibrogenesis. In this
      study, we investigated the pathophysiological significance of ET-1 and
      involvement of RhoA, a member of the Rho GTPases, in hypertrophic scar/keloid
      formation. We found that ET-1 expression on dermal microvascular endothelial
      cells (ECs) in hypertrophic scars and keloids was higher than that in normal skin
      and mature scars. We also confirmed that ET-1 induced myofibroblast
      differentiation and collagen synthesis in cultured human dermal fibroblasts
      through the RhoA/Rho-kinase pathway. Finally, since hypertrophic scar/keloid
      formation was most prominent in areas exposed to mechanical stretch, we examined
      how mechanical stretch affected ET-1 secretion in human dermal microvascular ECs,
      and found that mechanical stretch increased ET-1 gene expression and secretion
      from ECs. Taken together, these results suggest that dermal microvascular ECs
      release ET-1 in response to mechanical stretch, and thereby contribute to the
      formation of hypertrophic scars and keloids through the RhoA/Rho-kinase pathway.

PMID- 27892647
TI  - Recent Progress in the Development of Printed Thin-Film Transistors and Circuits
      with High-Resolution Printing Technology.
AB  - Printed electronics enable the fabrication of large-scale, low-cost electronic
      devices and systems, and thus offer significant possibilities in terms of
      developing new electronics/optics applications in various fields. Almost all
      electronic applications require information processing using logic circuits.
      Hence, realizing the high-speed operation of logic circuits is also important for
      printed devices. This report summarizes recent progress in the development of
      printed thin-film transistors (TFTs) and integrated circuits in terms of
      materials, printing technologies, and applications. The first part of this report
      gives an overview of the development of functional inks such as semiconductors,
      electrodes, and dielectrics. The second part discusses high-resolution printing
      technologies and strategies to enable high-resolution patterning. The main focus
      of this report is on obtaining printed electrodes with high-resolution patterning
      and the electrical performance of printed TFTs using such printed electrodes. In
      the final part, some applications of printed electronics are introduced to
      exemplify their potential.

PMID- 27892648
TI  - Milking performance evaluation and factors affecting milking claw vacuum levels
      with flow simulator.
AB  - Milking performance of milking machines that matches the production capability of
      dairy cows is important in reducing the risk of mastitis, particularly in high
      producing cows. This study used a simulated milking device to examine the milking
      performance of the milking system of 73 dairy farms and to analyze the factors
      affecting claw vacuum. Mean claw vacuum and range of fluctuation of claw vacuum
      (claw vacuum range) were measured at three different flow rates: 5.7, 7.6 and 8.7
      kg/min. At the highest flow rate, only 16 farms (21.9%) met both standards of
      mean claw vacuum >=35 kPa and claw vacuum range <= 7 kPa, showing that milking
      systems currently have poor milking performance. The factors affecting mean claw
      vacuum were claw type, milk-meter and vacuum shut-off device; the factor
      affecting claw vacuum range was claw type. Examination of the milking performance
      of the milking system using a simulated milking device allows an examination of
      the performance that can cope with high producing cows, indicating the
      possibility of reducing the risk of mastitis caused by inappropriate claw vacuum.

PMID- 27892649
TI  - Thresholding methods for lesion segmentation of basal cell carcinoma in
      dermoscopy images.
AB  - PURPOSE: Algorithms employed for pigmented lesion segmentation perform poorly on
      dermoscopy images of basal cell carcinoma (BCC), the most common skin cancer. The
      main objective was to develop better methods for BCC segmentation. METHODS:
      Fifteen thresholding methods were implemented for BCC lesion segmentation. We
      propose two error metrics that better measure the type II error: Relative XOR
      Error and Lesion Capture Ratio. RESULTS: On training/test sets of 305 and 34 BCC
      images, respectively, five new techniques outperform two state-of-the-art methods
      used in segmentation of melanomas, based on the new error metrics. CONCLUSION:
      The proposed algorithms, which include solutions for image vignetting correction
      and border expansion to achieve dermatologist-like borders, provide more
      inclusive and feature-preserving border detection, favoring better BCC
      classification accuracy, in future work.

PMID- 27892650
TI  - Application of Bayesian hierarchical models for phase I/II clinical trials in
      oncology.
AB  - Treatment during cancer clinical trials sometimes involves the combination of
      multiple drugs. In addition, in recent years there has been a trend toward phase
      I/II trials in which a phase I and a phase II trial are combined into a single
      trial to accelerate drug development. Methods for the seamless combination of
      phases I and II parts are currently under investigation. In the phase II part,
      adaptive randomization on the basis of patient efficacy outcomes allocates more
      patients to the dose combinations considered to have higher efficacy. Patient
      toxicity outcomes are used for determining admissibility to each dose combination
      and are not used for selection of the dose combination itself. In cases where the
      objective is not to find the optimum dose combination solely for efficacy but
      regarding both toxicity and efficacy, the need exists to allocate patients to
      dose combinations with consideration of the balance of existing trade-offs
      between toxicity and efficacy. We propose a Bayesian hierarchical model and an
      adaptive randomization with consideration for the relationship with toxicity and
      efficacy. Using the toxicity and efficacy outcomes of patients, the Bayesian
      hierarchical model is used to estimate the toxicity probability and efficacy
      probability in each of the dose combinations. Here, we use Bayesian moving
      reference adaptive randomization on the basis of desirability computed from the
      obtained estimator. Computer simulations suggest that the proposed method will
      likely recommend a higher percentage of target dose combinations than a
      previously proposed method.

PMID- 27892651
TI  - Fumarate Copolymer-Chitosan Cross-Linked Scaffold Directed to Osteochondrogenic
      Tissue Engineering.
AB  - Natural and synthetic cross-linked polymers allow the improvement of
      cytocompatibility and mechanical properties of the individual polymers. In
      osteochondral lesions of big size it will be required the use of scaffolds to
      repair the lesion. In this work a borax cross-linked scaffold based on fumarate
      vinyl acetate copolymer and chitosan directed to osteochondrondral tissue
      engineering is developed. The cross-linked scaffolds and physical blends of the
      polymers are analyzed in based on their morphology, glass transition temperature,
      and mechanical properties. In addition, the stability, degradation behavior, and
      the swelling kinetics are studied. The results demonstrate that the borax cross
      linked scaffold exhibits hydrogel behavior with appropriated mechanical
      properties for bone and cartilage tissue regeneration. Bone marrow progenitor
      cells and primary chondrocytes are used to demonstrate its osteo- and
      chondrogenic properties, respectively, assessing the osteo- and chondroblastic
      growth and maturation, without evident signs of cytotoxicity as it is evaluated
      in an in vitro system.

PMID- 27892652
TI  - Aliphatic Polyethers with Sulfate, Carboxylate, and Hydroxyl Side Groups-Do They
      Show Anticoagulant Properties?
AB  - There is increasing interest in the synthesis of low molecular weight heparin and
      heparan sulfate mimetic polymers because of their various potential biomedical
      applications. The functional activity of heparin and heparan sulfate is believed
      to arise from the presence of a number of functional groups, such as hydroxyl,
      carboxylate and sulfate groups. The design and synthesis of novel heparin-mimetic
      polymers with a particular functionality poses a formidable challenge and
      requires carefully control of the selective conversion of functional groups on
      the polymer chain. Here, this study describes a simple and efficient synthetic
      protocol for the preparation of heparin-mimetic linear polyglycidol copolymers
      based on the selective conversion of primary hydroxyl groups to carboxylic acids
      under ruthenium-catalyzed selective dehydrogenation in basic aqueous solution. To
      achieve the anticoagulant activity of these polymers, primary hydroxyl groups are
      selectively converted to sulfate groups. The anticoagulant activity of the
      heparin mimics is studied by rotational thromboelastometry using EXTEM and INTEM
      assays. The environmentally benign process described herein provides an
      attractive route for the synthesis of heparin-mimetic polymers with tailored
      functions such as anticoagulant activity.

PMID- 27892653
TI  - Low baseline levels of NK cells may predict a positive response to ipilimumab in
      melanoma therapy.
AB  - The introduction of immune checkpoint blockade (ICB) has been a breakthrough in
      the therapy of metastatic melanoma. The influence of ICB on T-cell populations
      has been studied extensively, but little is known about the effect on NK cells.
      In this study, we analysed the relative and absolute amounts of NK cells and of
      the subpopulations of CD56dim and CD56bright NK cells among the peripheral blood
      mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and
      under treatment with ipilimumab or pembrolizumab by flow cytometry. In 15 (47%)
      patients, an abnormal low amount of NK cells was found at baseline. Analysis of
      the subpopulations showed also low or normal baseline levels for CD56dim NK
      cells, whereas the baseline levels of CD56bright NK cells were either normal or
      abnormally high. The relative and absolute amounts of NK cells and of CD56dim and
      CD56bright NK cell subpopulations in patients with a normal baseline did not
      change under treatment. However, patients with a low baseline of NK cells and
      CD56dim NK cells showed a significant increase in these immune cell subsets, but
      the amounts remained to be lower than the normal baseline. The amount of
      CD56bright NK cells was unaffected by treatment. The baseline levels of NK cells
      were correlated with the number of metastatic organs. Their proportion increased,
      whereas the expression of NKG2D decreased significantly when more than one organ
      was affected by metastases. Low baseline levels of NK cells and CD56dim NK cells
      as well as normal baseline levels of CD56bright NK cells correlated significantly
      with a positive response to ipilimumab but not to pembrolizumab. Survival curves
      of patients with low amounts of CD56dim NK cells treated with ipilimumab showed a
      trend to longer survival. Normal baseline levels of CD56bright NK cells were
      significantly correlated with longer survival as compared to patients with high
      baseline levels. In conclusion, analysis of the amounts of total NK cells and of
      CD56dim and CD56bright NK cells subpopulations at baseline may help to predict
      the outcome of treatment with ipilimumab.

PMID- 27892654
TI  - Injectable Polysaccharide Hydrogels as Biocompatible Platforms for Localized and
      Sustained Delivery of Antibiotics for Preventing Local Infections.
AB  - Biocompatible and antibacterial hydrogels have received increasing attention for
      preventing local bacterial infections. In this study, a type of polysaccharide
      hydrogels is prepared via the Schiff-based reaction at physiological conditions.
      The gelation time and mechanical property of the hydrogels are found to be
      dependent on the polysaccharide concentration and the polysaccharide weight
      ratio. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and
      live/dead assay indicate that the hydrogels display nontoxicity in vitro. After
      subcutaneous injection into rats, the hydrogels exhibit an acceptable
      biocompatibility in vivo. Furthermore, the bacterial inhibition tests by shaking
      flask method and agar disc-diffusion method demonstrate that the ceftriaxone
      sodium-loaded hydrogels have remarkable antibacterial properties in vitro. The in
      vivo anti-infective tests further display that the antibiotic-loaded hydrogels
      display excellent anti-infective efficacies in both superficial and deep tissue
      infection. Consequently, the injectable and biocompatible polysaccharide
      hydrogels may serve as promising platforms for localized, sustained delivery of
      antibiotics for preventing local infections.

PMID- 27892655
TI  - 3D Printed Polycaprolactone Carbon Nanotube Composite Scaffolds for Cardiac
      Tissue Engineering.
AB  - Fabrication of tissue engineering scaffolds with the use of novel 3D printing has
      gained lot of attention, however systematic investigation of biomaterials for 3D
      printing have not been widely explored. In this report, well-defined structures
      of polycaprolactone (PCL) and PCL- carbon nanotube (PCL-CNT) composite scaffolds
      have been designed and fabricated using a 3D printer. Conditions for 3D printing
      has been optimized while the effects of varying CNT percentages with PCL matrix
      on the thermal, mechanical and biological properties of the printed scaffolds are
      studied. Raman spectroscopy is used to characterise the functionalized CNTs and
      its interactions with PCL matrix. Mechanical properties of the composites are
      characterised using nanoindentation. Maximum peak load, elastic modulus and
      hardness increases with increasing CNT content. Differential scanning calorimetry
      (DSC) studies reveal the thermal and crystalline behaviour of PCL and its CNT
      composites. Biodegradation studies are performed in Pseudomonas Lipase enzymatic
      media, showing its specificity and effect on degradation rate. Cell imaging and
      viability studies of H9c2 cells from rat origin on the scaffolds are performed
      using fluorescence imaging and MTT assay, respectively. PCL and its CNT
      composites are able to show cell proliferation and have the potential to be used
      in cardiac tissue engineering.

PMID- 27892656
TI  - Cytochrome P450 Bioconjugate as a Nanovehicle for Improved Chemotherapy
      Treatment.
AB  - Cancer is still a growing public health problem, especially breast cancer that is
      one of the most important cancers in women. Chemotherapy, even though a
      successful treatment, is accompanied by severe side effects. Moreover, most of
      the drugs used for chemotherapy are administered as prodrugs and need to be
      transformed to the active form by cytochromes P450 (CYPs). In addition,
      increasing numbers of cancer tissues show lower CYP activity than the surrounding
      healthy tissues in which prodrugs are preferentially activated causing
      cytotoxicity. Here, the design of a functionalized cytochrome P450 bioconjugate
      is reported as nanovehicle for the enzyme direct delivery to the tumor tissue in
      order to improve the local drug activation. MCF-7 breast cancer cells are treated
      with CYP-polyethylene glycol bioconjugate functionalized folic acid, where it
      activates the prodrug tamoxifen and significantly reduces the dose of tamoxifen
      needed to kill the tumor cells. The CYP bioconjugate covered with polyethylene
      glycol shows no immunogenic activity. The advantages of increasing the site
      specific CYP activity in tumor tissues are discussed.

PMID- 27892657
TI  - Effective delivery of porphyrazine photosensitizers to cancer cells by polymer
      brush nanocontainers.
AB  - Efficient drug delivery can be assigned to tasks that attract the most acute
      attention of researchers in the field of anticancer drug design. We have reported
      the first case of using amphiphilic polymer brushes as nanocontainers for
      photosensitizer delivery to cancer cells. Regular graft-copolymers of hydrophobic
      polyimides with hydrophilic polymethacrylic acid side chains were loaded with
      photosensitive dye tetra(4-fluorophenyl)tetracyanoporphyrazine (Pz) providing a
      sufficiently stable homogeneous fraction of fluorescent Pz-loaded nanoparticles
      with a size of 100-150 nm. Pz-loaded polymer brushes were substantially more
      efficient for Pz delivery into cells compared with other types of particles
      examined, Pz-polyethyleneglycol and Pz-methylcellulose. In vivo, an efficient Pz
      delivery to tumor can also be expected since the Pz-PB particle size is in the
      optimal range for passive targeting. Pz-PB showed pronounced photodynamic
      activity, while, that is important, in the absence of irradiation the PB carrier
      itself was significantly less toxic than the dye itself. Summing up, water
      soluble polymer brushes with polyimide backbones and polymethacrylic acid side
      chains can be regarded as a novel type of nanocontainers providing efficient
      intracellular drug delivery for photodynamic therapy of cancers.

PMID- 27892659
TI  - University Students with Dyslexia: A Qualitative Exploratory Study of Learning
      Practices, Challenges and Strategies.
AB  - People with dyslexia are vastly under-represented in universities (Katusic et
      al., , Richardson & Wydell, ; Stampoltzis & Polychronopoulou, ). This situation
      is of concern for modern societies that value social justice. This study was
      designed to explore learning experiences of university students with dyslexia and
      factors that could contribute to their success. Thirteen students with dyslexia
      and 20 non-dyslexic peers were interviewed about their university learning
      experiences using a semi-structured qualitative approach. Students with dyslexia
      described engaging in learning activities intensively, frequently and
      strategically. They reported challenges and strengths relating to study skills,
      lectures, assessments, technology and support services. They also described
      helpful strategies including self-directed adaptive techniques, provisions from
      lecturers and assistance from the university. These findings suggest that
      students with dyslexia experience broad challenges at university, but helpful
      strategies may be available. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27892660
TI  - Asia Pacific Journal of Cancer Prevention MEDLINE/PubMed Listing and Solution to
      the PRESERVATION Issue

PMID- 27892658
TI  - Occupational syncarcinogenesis in the skin - combined effects of two carcinogens
      from the German occupational disease list.
AB  - BACKGROUND: Though scientifically undisputed, cutaneous syncarcinogenesis is not
      reflected in German occupational disease (OD) regulations, which tend to be
      guided by the tenet of monocausality. Recognition of nonmelanoma skin cancer
      (NMSC) and its precursor lesions as OD requires individual assessment as to
      whether the requirements pursuant to either OD 5103 (occupational exposure to
      natural UV radiation) or OD 5102 (occupational exposure to polycyclic aromatic
      hydrocarbons) are fulfilled. METHODS: Retrospective analysis of 28 patients
      (median age 72.5 years) with NMSC and respective precursor lesions who had been
      occupationally exposed to natural UV radiation and polycyclic aromatic
      hydrocarbons. All cases had undergone expert medical assessment between September
      2012 and September 2015. RESULTS: According to our assessments, all 28 cases met
      the occupational requirements pursuant to OD 5103 and 5102. In 26 cases (93 %),
      we recommended recognition of skin cancer as occupational disease pursuant to
      both OD 5103 and OD 5102. The competent occupational insurance association (BG)
      followed our recommendation in four cases. In eight cases, recognition was solely
      based on OD 5103; in ten cases, only on OD 5102. Four cases were denied
      recognition. CONCLUSIONS: Following adequate cumulative occupational exposure to
      natural UV light as well as occupational exposure to polycyclic aromatic
      hydrocarbons, NMSC or its precursor lesions arising in UV-exposed areas should be
      reported to the competent occupational insurance association as "OD 5103 and 5102
      in terms of syncarcinogenesis". Apart from the fact that the ensuing recognition
      proceedings will be able to more adequately reflect real-life workplace
      conditions, filing a report pursuant to both ODs also allows for recognition of
      basal cell carcinoma as occupational disease. According to current regulations,
      this would not be possible, if the assessment were solely based on OD 5103.

PMID- 27892661
TI  - Infertility in Pediatric Cancer Survivors: A Necessary Evil or a Potentially
      Avoidable Sequel?

PMID- 27892662
TI  - Effectiveness of Teach-Back Self-Management Training Program on Happiness of
      Breast Cancer Patients
AB  - Self-management training is one of the ways to empower patients to cope with
      disease. The aim of this before-and-afterquasi-experimental study was to
      determine effects of a teach-back self-management training method on breast
      cancerpatient happiness. Fifty breast cancer patients who visited the Park-e
      Neshat Limited Surgery Clinic in Kerman, Iranwere randomly divided into
      intervention and control groups after convenience sampling and checking for
      inclusioneligibility. Data were collected using a demographic questionnaire and
      the Oxford Happiness Inventory before andafter teach-back training and analyzed
      using SPSS 23. Findings showed no significant difference between meanhappiness
      scores in the two groups before the intervention. However, after the
      intervention, the mean happiness scorein the intervention group increased from
      37.2 to 62.9, while it decreased from 41.4 to 29.8 in the control group.
      Thesechanges were statistically significant (p<0.001). Even after controlling for
      the effect of confounding factors such asresidence location and history of cancer
      education, the observed differences between the groups were
      statisticallysignificant (p<0.001). A teach-back self-management training program
      can increase happiness levels in breast cancerpatients. Therefore, the use of
      this method is recommended to improve self-management and increase happiness.

PMID- 27892663
TI  - Diagnosis of Malignant Biliary Strictures: Conventional or Negative Pressure
      Brush Cytology?
AB  - Background/Objective: The aim of this study was to perform a comparative
      evaluation of the yields of conventionalbrush cytology and brush cytology with
      negative pressure in the diagnosis of malignant biliary strictures. Methods:
      Atotal of 132 consecutive patients undergoing endoscopic were identified. Of
      these, 88.0 had brush cytology after ERCPand 44 were Brush cytology with negative
      pressure. Retrograde cholangiopancreatography (ERCP) including brushcytology and
      brush cytology with negative pressure in patients with biliary strictures between
      2012-2015. Endoscopicretrograde cholangiography was performed with a standard
      videoduodenoscope Olympus TFJ 160-R (Olympus,Hamburg, Germany) and brush cytology
      with a Cook medical Double Lumen Biliary BrushTM (Cytology). Meansand standard
      frequencies were used to calculate variables. Results: Positive results for
      malignancy were obtained in22 of 88 patients (25%) by brush cytology and 31 of 44
      patients (70.4 %) by brush cytology with negative pressure.Conclusions:
      Sensitivity of cytology sampling could be maximized by negative pressure during
      ERCP.

PMID- 27892664
TI  - Breast Cancer and Modifiable Lifestyle Factors in Argentinean Women: Addressing
      Missing Data in a Case-Control Study
AB  - A number of studies have evidenced the effect of modifiable lifestyle factors
      such as diet, breastfeeding and nutritionalstatus on breast cancer risk. However,
      none have addressed the missing data problem in nutritional epidemiologic
      researchin South America. Missing data is a frequent problem in breast cancer
      studies and epidemiological settings in general.Estimates of effect obtained from
      these studies may be biased, if no appropriate method for handling missing data
      isapplied. We performed Multiple Imputation for missing values on covariates in a
      breast cancer case-control study ofCordoba (Argentina) to optimize risk
      estimates. Data was obtained from a breast cancer case control study from 2008to
      2015 (318 cases, 526 controls). Complete case analysis and multiple imputation
      using chained equations were themethods applied to estimate the effects of a
      Traditional dietary pattern and other recognized factors associated withbreast
      cancer. Physical activity and socioeconomic status were imputed. Logistic
      regression models were performed.When complete case analysis was performed only
      31% of women were considered. Although a positive associationof Traditional
      dietary pattern and breast cancer was observed from both approaches (complete
      case analysis OR=1.3,95%CI=1.0-1.7; multiple imputation OR=1.4, 95%CI=1.2-1.7),
      effects of other covariates, like BMI and breastfeeding,were only identified when
      multiple imputation was considered. A Traditional dietary pattern, BMI and
      breastfeeding areassociated with the occurrence of breast cancer in this
      Argentinean population when multiple imputation is appropriatelyperformed.
      Multiple Imputation is suggested in Latin America's epidemiologic studies to
      optimize effect estimates inthe future.

PMID- 27892665
TI  - Thyroid Function after Postoperative Radiation Therapy inPatients with Breast
      Cancer
AB  - Objective: The aim of this study was to assess thyroid function in breast cancer
      patients exposed to therapeuticexternal beam radiation. The focus was on possible
      progressive changes and any relationships between the incidence ofprimary
      hypothyroidism, the time required to become hypothyroid, and factors such as
      chemotherapy, hormonotherapyand immunotherapy. Materials and Methods: Seventy
      females undergoing 3D conformal and IMRT radiation therapyfor breast cancers were
      enrolled in a non-randomized prospective study. The patients was divided into two
      groups:those after mastectomy or breast conserving surgery (BCS) were irradiated
      to a scar of the chest wall/breast and theipsilateral supraclavicular and the
      axillary areas (supraclavicular radiotherapy group - SC-RT group - 32 patients)
      andthe control group receiving adjuvant chest wall/breast RT only (BCT group - 38
      patients).The total doses were 50.0to 70 Gy in 5 to 7 weeks. The median follow-up
      term was 24 months (range, 1-40 months). Thyroid function wasevaluated by
      measuring thyroid stimulating hormone (TSH), free thyroxine (fT4), and free
      triiodothyronine (fT3) levels.The minimum, maximum and mean thyroid gland doses
      for 20 Gy (V20) were calculated for all patients. Results:Statistically
      significant results were obtained for the SC-RT group. Two yearsa fter the end of
      RT the chance of an eventwas increased in 6% of the population (p=0.009) in the
      SC-RT group. In the BCT group no significance was noted. Nostatistically
      significant differences were found for V20, chemio-, immunotherapy and
      hormonotherapy or Ki67 values(p=0.12). No significant results were obtained for
      development of hypothyroidism and clinical factors (age, thyroidvolume, treatment
      modalities). Conclusion: Radiotherapy is associated with a higher incidence of
      thyroid toxicity inbreast cancer patients. Routine thyroid function monitoring
      should be recommended in such cases.

PMID- 27892666
TI  - Mantle Cell Lymphoma: A North Indian Tertiary Care CentreExperience
AB  - Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma,
      with a pathognomonicchromosomal translocation t (11;14). Prognosis is uniformly
      dismal but there is a paucity of information on MCL fromIndia. Materials and
      methods: We retrospectively analysed clinicopathological information on all
      treated patients withMCL at our centre. STATA 14.0 was used for analysis.
      Survival was assessed by Kaplan-Meier analysis and the Cox'sproportional hazards
      method. Statistical significance was defined as a P value of < 0.05. Results:
      Fifty-one patients withMCL were reviewed. The median age at presentation was 57.0
      years. Extranodal involvement was seen in 39.0 (74.0%)while bone marrow
      positivity at presentation was found in 27.0 (54.0%). Initial treatment was
      chemotherapy with orwithout rituximab. Patients receiving rituximab-based therapy
      (n = 24) had 5-year progression-free survival (PFS) of 21.0(88.0%), compared with
      14.0 (61.0%) for those not receiving rituximab (n = 23, P = 0.036). Twenty-three
      patients werealive with a median follow-up of 20.7 months (range 2.5-89.2). PFS
      at 1 and 2 years was 51.0% and 27.0%, and overallsurvival (OS) 78.0% and 72.0%,
      respectively. Use of more than 2.0 lines of therapy, use of bendamustine
      rituximab,and high TLC (>10,000.0/cu.mm) significantly affected PFS. Conclusions:
      In our experience, MCL patients fromnorth India have an early age at
      presentation. When treated with regimens including rituximab results in an
      improvedresponse rate and PFS. This study provided comprehensive insights into
      the treatment of MCL in a developing country.

PMID- 27892667
TI  - Area-to-Area Poisson Kriging and Spatial Bayesian Analysisin Mapping of Gastric
      Cancer Incidence in Iran
AB  - Background: In many countries gastric cancer has the highest incidence among the
      gastrointestinal cancers and isthe second most common cancer in Iran. The aim of
      this study was to identify and map high risk gastric cancer regionsat the county
      level in Iran. Methods: In this study we analyzed gastric cancer data for Iran in
      the years 2003-2010. Areato-area Poisson kriging and Besag, York and Mollie (BYM)
      spatial models were applied to smoothing the standardizedincidence ratios of
      gastric cancer for the 373 counties surveyed in this study. The two methods were
      compared in termof accuracy and precision in identifying high risk regions.
      Result: The highest smoothed standardized incidence rate(SIR) according to area
      to-area Poisson kriging was in Meshkinshahr county in Ardabil province in north
      westernIran (2.4,SD=0.05), while the highest smoothed standardized incidence rate
      (SIR) according to the BYM model wasin Ardabil, the capital of that province
      (2.9,SD=0.09). Conclusion: Both methods of mapping, ATA Poisson krigingand BYM,
      showed the gastric cancer incidence rate to be highest in north and north-west
      Iran. However, area-to-areaPoisson kriging was more precise than the BYM model
      and required less smoothing. According to the results obtained,preventive
      measures and treatment programs should be focused on particular counties of Iran.

PMID- 27892668
TI  - Transanal endoscopic microsurgery in the treatment of large rectal adenomas.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEM) is a minimally invasive
      technique allowing to excise large rectal adenomas by local approach. This study
      shows the feasibility and results of a long term experience of TEM applied in
      this field. METHODS: A retrospective investigation was performed in patients
      affected by rectal adenomas (5-11 cm in diameter) who had undergone transanal
      endoscopic microsurgery from 1992 to 2015. A series of 207 patients met the
      inclusion criteria and were analyzed for characteristics, intraoperative and
      postoperative results and long-term follow-up. RESULTS: Median age was 71 years
      (52-83 years). Of the 207 total patients, 77 were women (37.2%) and 130 men
      (62.8%). Median distance from the anal verge was 8 cm (4-20 cm). Median size was
      6 cm, with lesion ranging from 5 to 11 cm in diameter. Median operative time was
      57 minutes (42-90 minutes). We observed 17 (8.2%) minor complications and 2
      (0.9%) major complication according to the Clavien-Dindo classification. We did
      not observe any intraoperative or post-operative mortality. Histological
      examination showed preoperative undiagnosed cancer in 8 (3.8%) cases in which the
      pathologist revealed adenocarcinoma staged as T1 Sm1 according to the Kikuchi
      classification. The median follow-up was 115 months (12-288 months). Six
      recurrences (2.9%), we observed with a median time for recurrence of 14 months.
      CONCLUSIONS: TEM provides excellent oncological outcomes in the treatment of
      large benign rectal lesions, ensuring a minimal risk of resection margin
      infiltration at pathological examination, and is associated with low risk of
      complications.

PMID- 27892669
TI  - The need of separating level III during axillary lymph node dissection in
      melanoma.

PMID- 27892670
TI  - Impact of Adjuvant Chemotherapy in Elderly Breast Patientsin Taiwan, A Hospital
      Based Study
AB  - Purpose: Decisions as to whether to provide adjuvant treatment in older breast
      cancer patients remains challenging.Side effects of chemotherapy have to be
      weighed against life expectancy, comorbidities, functional status, and frailty.To
      aid decision-making, we retrospectively analyzed 110 women with breast cancer
      treated with a curative intentionfrom 2006 to 2012. Survival data with clinical
      and pathological parameters were evaluated to address the role ofadjuvant
      chemotherapy in this study population. Method: A total of 110 elderly (>70 years)
      patients that receivedmastectomy at two hospitals in Taiwan were observed
      retrospectively for a medium of 51 months. After mastectomy,patients received
      conservative treatment or adjuvant chemotherapy, or hormone therapy following
      clinical guidelinesor physician's preference. Data were collected from the cancer
      registry system. Results: Median age at diagnosis was75.7 years. Thirty-five
      percent of patients received adjuvant chemotherapy, these having a significantly
      younger age(mean=74.0+/-5.3 vs 77.5+/-5.3, p<0.001) and higher tumor staging
      (p=0.003) compared with their non-chemotherapycounterparts.Five-year overall
      survival was non-significantly higher in patients who received adjuvant
      chemotherapy(with chemotherapy 64.2% vs without chemotherapy 62.6%, p=0.635),
      while five-year recurrence free survival wasnon-significantly lower (with
      chemotherapy 64.1% vs without chemotherapy 90.5%, p=0.80). Conclusions: In
      thisanalysis, adjuvant chemotherapy tended to be given to patients with a younger
      age and higher tumor staging at ourinstitute. It was not associated with any
      statistically significant improvement in survival and recurrence rate. Untilage
      specific recommendations are available, physicians must use their clinical
      judgment and assess the tumor biologywith the patient's comorbidities to make the
      best choice. Clinical trials focusing on this critical issue are warranted.

PMID- 27892671
TI  - Association between the XRCC3 Thr241Met Polymorphismand Gastrointestinal Cancer
      Risk: A Meta-Analysis
AB  - Background: The x-ray repair cross-complementing group 3 (XRCC3) encodes a
      protein involved in thehomologous recombination repair (HRR) pathway for double
      strand DNA repair. Associations of the XRCC3 Thr241Metpolymorphism with various
      cancers have been widely reported. However, published data on links between
      XRCC3Thr241Met and gastrointestinal (GI) cancer risk are inconsistent. Objective
      and Methods: A meta-analysis wasconducted to characterize the relationship
      between XRCC3 Thr241Met polymorphisms and GI cancer risk. Pooledodds ratios (ORs)
      and 95.0% confidence intervals were assessed using random- or fixed- effect
      models for 28.0 relevantarticles with 30.0 studies containing 7,649.0 cases and
      11,123.0 controls. Results: The results of the overall meta-analysissuggested a
      borderline association between the XRCC3 Thr241Met polymorphism and GI cancer
      susceptibility (T vs.C: OR=1.18, 9 % CI=1.0-1.4, POR=0.04; TT vs. CT+CC: OR=1.3,
      95 % CI=1.0-1.6, POR=0.04). After removingstudies not conforming to Hardy
      Weinberg equilibrium (HWE), however, this association disappeared (T vs.
      C:OR=1.00, 95 % CI=0.9-1.1, POR=0.96; TT vs. CT+CC: OR=0.9, 95 % CI=0.8-1.1,
      POR=0.72). When stratified byethnicity, source of controls or cancer type,
      although some associations between XRCC3 Thr241Met polymorphismand GI cancer
      susceptibility were detected, these associations no longer existed after removing
      studies not conformingto HWE. Conclusion: Our meta-analysis suggests that the
      XRCC3 Thr241Met polymorphism is not associated withrisk of GI cancer based on
      current evidence.

PMID- 27892672
TI  - Effects of Copper Reduction on Angiogenesis-Related Factorsin Recurrent
      Glioblastoma Cases
AB  - Purpose? To evaluate the therapeutic effects of copper reduction on angiogenesis
      related factors in patients withglioblastoma multiforme treated by gamma knife
      radiosurgery. Materials and Methods? In the present block randomized,placebo
      controlled trial, fifty eligible patients with a diagnosis of glioblastoma
      multiforme who were candidates forgamma knife radiosurgery were randomly assigned
      into two groups to receive daily either 1gr penicillamine and a lowcopper diet or
      placebo for three months. The intervention started on the same day as gamma knife
      radiosurgery. Seruminterleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha),
      vascular endothelial growth factor (VEGF) and copper levelswere measured at
      baseline and after the intervention. The serum copper level was used as the final
      index of compliancewith the diet. In order to control probable side effects of
      intervention, laboratory tests were conducted at the beginning,middle and end of
      the study. Results? The patients had a mean age and Karnofsky Performance Scale
      of 43.7 yearsand 75 respectively. Mean serum copper levels were significantly
      reduced in intervention group. Mean survival timewas 18.5 months in intervention
      group vs. 14.9 in placebo group. VEGF and IL-6 levels in the intervention
      groupwere also significantly reduced compared to the placebo group and TNF-alpha
      increased less. Conclusions? It seems thatreducing the level of copper in the
      diet and dosing with penicillamine leads to decline of angiogenesis-related
      factorssuch as VEGF, IL-6 and TNF-alpha. Approaches targeting angiogenesis may
      improve survival and can be used as a futuretherapeutic strategy.

PMID- 27892673
TI  - Survival Rate of Breast Cancer in Iran: A Meta-Analysis
AB  - Background: There has not been a general estimation about survival rates of
      breast cancer cases in Iran. Therefore,the present study aimed to assess survival
      using a meta-analysis. Materials and Methods: International credibledatabases
      such as Scopus, Web of Science, PubMed, Science direct and Google Scholar and
      Iranian databases suchas Magiran, Irandoc and SID, from 1997 to 2015 were
      searched. All articles covering survival rate of breast cancerwere entered into
      the study without any limits. Quality assessment of the articles and data
      extraction were performedby two researchers using the modified STROBE checklist,
      which includes 12 questions. Articles with scores greaterthan 8 were included in
      the analysis. A limitation of this meta-analysis was different methods for
      presenting of resultsin the papers surveyed. Results: A total of 21 articles with
      a sample of 12,195 people were analyzed. The one-year,three-year, five-year and
      ten-year survival rates of breast cancer in Iran were estimated to be 95.8% (94.6
      97.0), 82.4%(79.0-85.8), 69.5% (64.5-74.5), 58.1% (39.6-76.6), respectively. The
      most important factors affecting survival of breastcancer were age, number of
      lymph nodes involved, size of the tumor and the stage of the disease. Conclusion:
      Thefive- and ten- year survival rates in Iran are lower than in developed
      countries. Conducting breast cancer screeningplan support (including regular
      clinical examination, mammography), public training and raising awareness should
      behelpful in facilitating early diagnosis and increasing survival rates for
      Iranian women.

PMID- 27892674
TI  - The Investigation of Risk Factors Impacting Breast Cancer in Guilan Province
AB  - Introduction: Breast cancer is multifactorial therefore more recognition of risk
      factors is important in its prevention.Objective: This study was conducted in
      order to determine the factors influencing breast cancer in women referred
      tohealth centers in Guilan province in 2015-2016. Method: In a case- control
      study, 225 women with breast cancer wereinvestigated. The control group consisted
      of 225 healthy women of the relatives (third-rank) whose phone numbers
      wereobtained from the patients. Data were collected through telephone interviews.
      Results: The risk of breast cancer raisedin women who have a family history of
      other cancers (OR= 3.5; 95% CI= 1.96-6.6) ,exposure to X-Ray (OR= 2.5; 95%CI=1.1
      5.5), having more than 4 children (OR= 2.695% CI=1.2-4.8), age more than 36 years
      at first pregnancy(OR=2.3;95% CI=0.7-5.1),primary level of education (OR= 5.4;95%
      CI=2.8-11.2) and inadequate intake of fruit (OR=1.5; 95%CI=1-2.2). Also, presence
      of the following factors reduced breast cancer risk: regular menstruation (OR=
      0.66; CI=0.4-0.9), duration of breastfeeding more than 12 months, less than 6
      months and 7-12 months (OR=0.23; 95% CI=0.09-0.59, OR=0.29; 95% CI=0.17-0.49 and
      OR=0.03; 95% CI=0.01-0.08) and parity (OR=0.4; 95% CI=0.27-0.83) In
      multiplelinear regression analysis of higher education (OR=0.16; 95% CI=0.03
      0.77), using contraceptives for more than 16years (OR=2.3; 95% CI=1.4-3.9),
      family history of other cancers (OR=6.1; 95% CI=1.9-19.3) and a history of X
      Rayexposure (OR=4.4; 95% CI=1.07-18.1) were considered as predictive factors.
      Conclusion: The results of this studyemphasize the importance of informing women
      about breast cancer risk factors. So, identification of these risk factorsis
      required as important means of prevention and treatment of breast cancer.

PMID- 27892675
TI  - Purification of Cucurbitacins D, E, and I from Ecballium Elaterium (L.) A. Rich
      Fruits and Study of Their Cytotoxic Effects on the AGS Cell Line
AB  - Background: The plant Ecballium elaterium (L.) A. Rich, belongs to the
      Cucurbitaceae family which occupiesan important position in traditional medicine
      prescriptions. It has been reported that a freeze-dried aqueous extractof E.
      elaterium fruits has cytotoxic effects on the AGS human stomach adenocarcinoma
      cell line. We here focusedon anticancer effects of the main chemicals purified
      from E. elaterium fruits. Materials and Methods: We isolatedcucurbitacins D, E,
      and I from chloroform, and ethyl acetate fractions of a methanolic extract of E.
      elaterium fruitsand assessed their cytotoxic effects on the AGS cell line by MTT
      assay. The methanolic extract was fractionated topetroleum ether, chloroform, and
      ethyl acetate fractions. The compounds isolated by column chromatography
      wereidentified by NMR spectroscopy. Results: After 24 h of incubation with AGS
      cells, the IC50 values were 0.3, 0.1, and0.5 MUg/ml for cucurbitacins D, E, and I
      respectively. Conclusions: This finding suggests that because of its
      cucurbitacins,E. elaterium fruit may have some cytotoxic effects on gastric
      cancer cells. Also, compared with D and I, cucurbitacinE showed greater potency
      in this regard.

PMID- 27892676
TI  - Palliative Care for Patients with Gynecologic Cancer in Japan:A Japan Society of
      Gynecologic Palliative Medicine (JSGPM)Survey
AB  - Purpose: To evaluate palliative care for patients with gynecologic cancer in
      Japan. Materials and Method: Aquestionnaire asking facility characteristics,
      systems to coordinate palliative care, current status of end-of-life
      care,provision of symptom relief, palliative radiation therapy and chemotherapy,
      and cases of death from gynecological cancer,was mailed to facilities treating
      gynecologic cancer. Results: A total of 115 facilities (29.3% of the total)
      respondedto the questionnaire. Of these, 33.0 (29.0%) had a palliative care ward.
      End-of-life care was managed by obstetriciansand gynecologists in 72.0% of the
      facilities. The site where end-of-life care was provided was most often a ward in
      thedepartment where the respondent worked. The waiting period for transfer to a
      hospice was 2 weeks or more in 52% offacilities. Before the start of primary
      treatment, pain control was managed by obstetrians and gynecologists in 98.0%
      offacilities. Palliative radiation therapy or chemotherapy was administered at
      93.9% and 92.0% of facilities, respectively.Of the 115 facilities, 34.0 (29.6%)
      reported cases of death from gynecological cancer. There were 1,134 cases of
      death.The median time between the last cycle of chemotherapy and death was 85
      days for all gynecological cancers. Theproportion of patients receiving
      chemotherapy in the last 30 and 14 days of life were 17.4% and 7.1%,
      respectively.Conclusions: This large-scale survey showed characteristics of
      palliative care given to patients with gynecologiccancer in Japan. Assessment of
      death cases showed that the median time between the last cycle of chemotherapy
      anddeath was relatively short.

PMID- 27892677
TI  - CCR5 Polymorphism as a Protective Factor for Hepatocellular Carcinoma in
      Hepatitis B Virus-Infected Iranian Patients
AB  - The CC chemokine receptor 5 (CCR5) delta 32 allele results in a nonfunctional
      form of the chemokine receptorand has been implicated in a variety of immune
      mediated diseases. CCR5Delta32 may also predispose one to chronicliver disease or
      be linked with resistance to HBV infection.This study was undertaken to
      investigate any associationbetween CCR5 polymorphism with resistance to hepatitis
      B or susceptibility to HBV infection. A total of 812 Iranianindividuals were
      enrolled into two groups: HBV infected cases (n=357), who were HBsAg-positive,
      and healthy controls(n=455). We assessed polymorphisms in the CCR5 gene using
      specific CCR5 oligonucleotide primers surroundingthe breakpoint deletion.
      Genotype distributions of the HBV infected cases and healthy controls were
      determined andcompared. The CCR5/CCR5 (WW) and CCR5/ CCR5Delta32 (W/D) genotypes
      were found in (98%) and (2%) of HBVinfected cases, respectively. The CCR5
      Delta32/ Delta32genotype was not found in HBV infected cases. Genotype
      distributionsof CCR5 in healthy controls were W/W genotype in (87.3%), W/D
      genotype in (11.2%) and D/D genotype in (1.5%).Heterozygosity for CCR5/
      CCR5Delta32 (W/D) in healthy controls was greater than in HBV infected cases
      (11.2% vs2%, p < 0.001). W/D and D/D genotypes were more prominent in healthy
      controls than in HBV infected cases. Thisstudy provides evidence that the
      CCR5Delta32 polymorphism may have a protective effect in resistance to HBV
      infectionat least in the Iranian population.

PMID- 27892678
TI  - Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR
      Mutations in Philadelphia-Negative Myeloproliferative Neoplasms
AB  - Background: The discovery of somatic acquired mutations of JAK2 (V617F) in
      Philadelphia-negativemyeloproliferative neoplasms (Ph-negative MPNs) including
      polycythemia vera (PV), essential thrombocythemia(ET), and primary myelofibrosis
      (PMF) has not only improved rational disease classification and
      prognosticationbut also brings new understanding insight into the pathogenesis of
      diseases. Dosage effects of the JAK2 (V617F)allelic burden in Ph-negative MPNs
      may partially influence clinical presentation, disease progression, and
      treatmentoutcome. Material and Methods: Pyrosequencing was performed to detect
      JAK2 (V617F) and MPL (W515K/L)and capillary electrophoresis to identify CALR exon
      9.0 mutations in 100.0 samples of Ph-negative MPNs (38.0 PV,55 ET, 4 PMF, and 3
      MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of
      PV,74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F)
      mutant allele burden (mutationalload > 50.0%) was predominantly observed in PV
      when compared with ET. Although a high level of JAK2 (V617F)allele burden was
      strongly associated with high WBC counts in both PV and ET, several hematological
      parameters(hemoglobin, hematocrit, and platelet count) were independent of JAK2
      (V617F) mutational load. MPL (W515K/L)mutations could not be detected whereas
      CALR exon 9.0 mutations were identified in 35.7% of patients with JAK2negative ET
      and 33.3% with JAK2 negative PMF. Conclusions: The JAK2 (V617F) allele burden may
      be involvedin progression of MPNs. Furthermore, a high level of JAK2 (V617F)
      mutant allele appears strongly associated withleukocytosis in both PV and ET.

PMID- 27892679
TI  - Anti-Heat Shock Protein-27 Antibody Levels in Women with Breast Cancer:
      Association with Disease Complications and Two-Year Disease-Free Survival
AB  - Background and Aim: Breast cancer is a major healthcare problem in women. There
      are many reports aboutup-regulation of Hsp27 in cancer tissues but less is known
      about the potential relationship between Hsp27 antibodylevels and breast cancer
      complications. We here investigated concentrations of serum Hsp27 antigen and
      antibodiesin subjects with and without breast cancer and assessed potential
      associations with two-year disease-free survival,histological grade and number of
      lymph nodes. Materials and Methods: Specifically, serum Hsp27 antigen and
      antibodylevels from 97 patients with breast cancer, and 65 healthy controls were
      determined by enzyme-linkedimmunosorbentassays (ELISAs). Results: Serum Hsp27 and
      antibody levels were significantly (p<0.001) higher in patients with breastcancer
      compared to the control group, but no relationship were found with two-year
      disease free survival, histologicalgrade or number of lymph nodes (p> 0.6, 0.2
      and 0.9 respectively). Conclusions: Elevated levels of Hsp27 antibodyoccur in
      patients with women with breast cancer but do not appear to be associated with
      the presence of disease clinicalcomplications.

PMID- 27892680
TI  - Artificial Light at Night and Cancer: Global Study
AB  - Background: Artificial light at night (ALAN) has been linked to increased risk of
      cancers in body sites like the breastand colorectum. However exposure of ALAN as
      an environmental risk factor and its relation to cancers in humans hasnever been
      studied in detail. Objective: To explore the association of ALAN with all forms
      of cancers in 158 countries.Materials and Methods: An ecological study
      encompassing global data was conducted from January to June 2015,with age
      standardized rates (ASR) of cancers as the outcome measure. ALAN, in the
      protected areas, as the exposurevariable, was measured with reference to the
      Protected Area Light Pollution Indicator (PALI) and the Protected AreaHuman
      Influence Indicator (PAHI). Pearson's correlations were calculated for PALI and
      PAHI with ASR of cancers for158 countries, adjusted for country populations,
      electricity consumption, air pollution, and total area covered by
      forest.Stratified analysis was conducted according to the country income levels.
      Linear regression was applied to measure thevariation in cancers explained by
      PALI and PAHI. Results: PALI and PAHI were positively associated with ASR of
      allforms of cancer, and also the four most common cancers (p < 0.05). These
      positive correlations remained statisticallysignificant for PAHI with all forms
      of cancer, lung, breast, and colorectal cancer after adjusting for confounders.
      Positiveassociations of PALI and PAHI with cancers varied with income level of
      the individual countries. Variation in all formsof cancers, and the four most
      common cancers explained by PALI and PAHI, ranged from 3.3 - 35.5%.
      Conclusion:Artificial light at night is significantly correlated for all forms of
      cancer as well as lung, breast, colorectal, and prostatecancers individually.
      Immediate measures should be taken to limit artificial light at night in the main
      cities around theworld and also inside houses.

PMID- 27892681
TI  - Evaluating the Existence of Small Compressed Binucleated Squamous Cells in ASC-H
AB  - Purpose: To evaluate the legitimacy of a diagnosis of ASC-H in 5 cases which were
      followed up monthly for over 2years with both cytology and HPV testing. Methods:
      Some 5 cases out of a total of 25.0 self-sampled Pap test patientsdiagnosed as
      ASC-H provided 119 specimens over 2 years, with HPV-DNA testing perormed using a
      E6 primer. Results:Cases 1, 2 and 3 showed SIL after the ASC-H diagnosis, while
      cases 4 and 5 showed and maintained NILM. Cases 1,2 and 3 were further
      characterized by small atypical compressed binucleated cells, in which HPV was
      detected by insitu PCR. Case 4 showed a high N/C ratio in cells in sheets with a
      mild increase in chromatin. Case 5 demonstrateda high N/C ratio in small cells
      with no increase in chromatin. Conclusion: The finding of a compressed
      binucleatedcells can define the difference between degenerated endocervical
      columnar cells and small atypical cells suggestiveof HSIL. When small compres

PMID- 27892682
TI  - Can Serum ICAM 1 distinguish pancreatic cancer from chronicpancreatitis?
AB  - Background and aim: Pancreatic cancer is the fourth leading cause of cancer
      related death worldwide, with anoverall 5-year survival of <5% mainly due to
      presence of advanced disease at time of diagnosis. Therefore developmentof valid
      biomarkers to diagnose pancreatic cancer in early stages is an urgent need. This
      study concerned the sensitivityand specificity of serum ICAM 1 versus CA 19-9 in
      differentiation between pancreatic cancer and healthy subjectsand acohort of
      patients with chronic pancreatitis with a focus on assessing validity in
      diagnosis of early stages ofpancreatic cancer. Methods: A cohort of 50 patients
      with histologically diagnosed pancreatic tumors, 27 patients withchronic
      pancreatitis, and 35 healthy controls were enrolled. Serum samples for
      measurement of CA19-9 and I-CAM 1were obtained from all groups and analyzed for
      significance regarding diagnosis and disease stage. Results: At a cutoff value of
      (878.5 u/ml) I-CAM 1 had 82% and 82.26% sensitivity and specificity for
      differentiation between cancerand non-cancer cases, with higher sensitivity and
      specificity than CA19-9 at different cut offs (CA19-9 sensitivity andspecificity
      ranged from 64-80% and 56.4 - 61.2% respectively). The AUC was 0.851 for I-CAM
      and 0.754 for CA19-9.Neither of the markers demonstrated significance for
      distinguishing between early and late cancer stages. Conclusion:ICAM 1 is a
      useful marker in differentiation between malignant and benign pancreatic
      conditions, and superior toCA19-9 in this regard. However, neither of the markers
      can be recommended for use in differentiation between earlyand late stage
      pancreatic cancers.

PMID- 27892683
TI  - Computer simulation for improving radio frequency (RF) heating uniformity of food
      products: A review.
AB  - Radio frequency (RF) heating has great potential for achieving rapid and
      volumetric heating in foods, providing safe and high-quality food products due to
      deep penetration depth, moisture self-balance effects, and leaving no chemical
      residues. However, the nonuniform heating problem (usually resulting in hot and
      cold spots in the heated product) needs to be resolved. The inhomogeneous
      temperature distribution not only affects the quality of the food but also raises
      the issue of food safety when the microorganisms or insects may not be controlled
      in the cold spots. The mathematical modeling for RF heating processes has been
      extensively studied in a wide variety of agricultural products recently. This
      paper presents a comprehensive review of recent progresses in computer simulation
      for RF heating uniformity improvement and the offered solutions to reduce the
      heating nonuniformity. It provides a brief introduction on the basic principle of
      RF heating technology, analyzes the applications of numerical simulation, and
      discusses the factors influencing the RF heating uniformity and the possible
      methods to improve heating uniformity. Mathematical modeling improves the
      understanding of RF heating of food and is essential to optimize the RF treatment
      protocol for pasteurization and disinfestation applications. Recommendations for
      future research have been proposed to further improve the accuracy of numerical
      models, by covering both heat and mass transfers in the model, validating these
      models with sample movement and mixing, and identifying the important model
      parameters by sensitivity analysis.

PMID- 27892685
TI  - Gut: A key player in the pathogenesis of type 2 diabetes?
AB  - The gut regulates glucose and energy homeostasis; thus, the presence of ingested
      nutrients into the gut activates sensing mechanisms that affect both glucose
      homeostasis and regulate food intake. Increasing evidence suggest that gut may
      also play a key role in the pathogenesis of type 2 diabetes which may be related
      to both the intestinal microbiological profile and patterns of gut hormones
      secretion. Intestinal microbiota includes trillions of microorganisms but its
      composition and function may be adversely affected in type 2 diabetes. The
      intestinal microbiota may be responsible of the secretion of molecules that may
      impair insulin secretion/action. At the same time, intestinal milieu regulates
      the secretion of hormones such as GLP-1, GIP, ghrelin, gastrin, somatostatin,
      CCK, serotonin, peptide YY, GLP-2, all of which importantly influence metabolism
      in general and in particular glucose metabolism. Thus, the aim of this paper is
      to review the current evidence on the role of the gut in the pathogenesis of type
      2 diabetes, taking into account both hormonal and microbiological aspects.

PMID- 27892684
TI  - Angiotensin receptor neprilysin inhibitor LCZ696: pharmacology, pharmacokinetics
      and clinical development.
AB  - Heart failure still has a significant disease burden with poor outcomes worldwide
      despite advances in therapy. The standard therapies have been focused on blockade
      of renin-angiotensin-aldosterone system with angiotensin-converting enzyme
      inhibitors, angiotensin receptor blockers and mineralocorticoid antagonists and
      the sympathetic nervous system with beta-blockers. The natriuretic peptide system
      is a potential counter-regulatory system that promotes vasodilatation and
      natriuresis. Angiotensin receptor neprilysin inhibitors are a new class drug
      capable of blocking the renin-angiotensin-aldosterone system and enhancing the
      natriuretic peptide system to improve neurohormonal balance. The success of the
      PARADIGM-HF trial with LCZ696 and its approval for heart failure treatment is
      likely to generate a paradigm shift. This review summarises the current knowledge
      of LCZ696 with a focus on pharmacology, pharmacokinetics and pharmacodynamics,
      mechanisms of action, clinical efficacy and safety.

PMID- 27892686
TI  - Tobacco and the Malays: ethnicity, health and the political economy of tobacco in
      Malaysia.
AB  - OBJECTIVES: To identify the historical nexus between Malaysia's largest and
      politically dominant ethnic group and the political economy of tobacco, and to
      consider the implications of this connection for tobacco control. DESIGN: Primary
      and secondary documentary sources in both English and Malay were analysed to
      illuminate key events and decisions, and the discourse of industry and
      government. Sources included: speeches by Malaysian political and industry
      actors; tobacco industry reports, press releases and websites; government
      documents; World Health Organization (WHO) tobacco control literature; and press
      reports. RESULTS: Malays have the highest smoking prevalence among Malaysia's
      major ethnic groups. The tobacco industry has consistently been promoted as
      furthering Malay economic development. Malays play the major role in growing and
      curing. Government-owned Malay development trusts have been prominent investors
      in tobacco corporations, which have cultivated linkages with the Malay elite. The
      religious element of Malay ethnicity has also been significant. All Malays are
      Muslim, and the National Fatwa Council has declared smoking to be haram
      (forbidden); however, the Government has declined to implement this ruling.
      CONCLUSION: Exaggerated claims for the socio-economic benefits of tobacco
      production, government investment and close links between tobacco corporations
      and sections of the Malay elite have created a conflict of interest in public
      policy, limited the focus on tobacco as a health policy issue among Malays and
      retarded tobacco control policy. More recently, ratification of the WHO Framework
      Convention on Tobacco Control, regional free trade policies reducing the numbers
      of growers, concerns about smoking from an Islamic viewpoint, and anxieties about
      the effects of smoking upon youth have increasingly challenged the dominant
      discourse that tobacco furthers Malay interests. Nevertheless, the industry
      remains a formidable political and economic presence in Malaysia that is likely
      to continue to proclaim that its activities coincide with Malay socio-economic
      interests.

PMID- 27892687
TI  - Three new drimane sesquiterpenoids from cultures of the fungus Penicillium sp.
AB  - Three new drimane sesquiterpenoids, 12-hydroxyalbrassitriol (1), drim-8(12)-en
      6beta,7alpha, 9alpha,11-tetraol (2), and drim-68(12)-dien-9alpha,11-diol (3),
      along with one known analog albrassitriol (4), were isolated from cultures of the
      tin mine tailings-associated fungus Penicillium sp. The new structures were
      determined on the basis of extensive spectroscopic analyses. All compounds were
      tested for their cytotoxicities against five human cancer cell lines.

PMID- 27892688
TI  - Secondary metabolites from Colletotrichum capsici, an endophytic fungus derived
      from Siegesbeckia pubescens Makino.
AB  - A rare new tremulane sesquiterpenoid analogue, 11,12-epoxy-5,6-seco-1,6(13)
      tremuladien-5,12-olide (1), together with five known altenuene derivatives (2-6)
      was isolated from the cultures of Colletotrichum capsici, which was isolated as
      an endophytic fungus from fresh leaves of Siegesbeckia pubescens Makino
      (Compositae). Their structures were elucidated by means of spectroscopic methods
      and comparison with literature data. All compounds isolated were reported for the
      first time from the fungus C. capsici.

PMID- 27892689
TI  - Biofilm inhibitors targeting the outer membrane protein A of Pasteurella
      multocida in swine.
AB  - Pasteurella multocida (Pm) is the causative agent of atrophic rhinitis in swine.
      This study aimed to discover biofilm inhibitors against swine Pm to counteract
      antibiotic resistance and decrease virulence. The virulence factor outer membrane
      protein A (OmpA) was targeted. A library of drugs approved by the Food and Drug
      Administration (FDA) was used to perform virtual screening against PmOmpA. The
      top-scoring compounds had no effect on the growth of Pm serotype A or D.
      Mycophenolate mofetil showed the highest efficacy in inhibiting biofilm formation
      by Pm serotype A, with an IC50 of 7.3 nM. For Pm serotype D, indocyanine green
      showed the highest effect at an IC50 of 11.7 nM. Nevertheless, these compounds
      had no effect on an established biofilm of Pm. This study offers an alternative
      way to prevent biofilm formation by Pm that could also be applied to other
      pathogens.

PMID- 27892690
TI  - Ethnic differences in women's use of mental health services: do social networks
      play a role? Findings from a national survey.
AB  - OBJECTIVES: The reasons for ethnic differences in women's mental health service
      use in England remain unclear. The aims of this study were to ascertain: ethnic
      differences in women's usage of mental health services, if social networks are
      independently associated with service use, and if the association between women's
      social networks and service use varies between ethnic groups. DESIGN: Logistic
      regression modelling of nationally representative data from the Ethnic Minority
      Psychiatric Illness Rates in the Community (EMPIRIC) survey conducted in England.
      The analytic sample (2260 women, aged 16-74 years) was drawn from the
      representative subsample of 2340 women in EMPIRIC for whom data on mental health
      services, and social networks were available. RESULTS: Pakistani and Bangladeshi
      women were less likely than White women to have used mental health services
      (Pakistani OR = 0.23, CI = 0.08-0.65, p = .005; Bangladeshi OR = 0.25, CI = 0.07
      0.86, p = .027). Frequent contact with relatives reduced mental health service
      use (OR = 0.45, CI = 0.23-0.89, p = .023). An increase in perceived inadequate
      support in women's close networks was associated with increased odds of using
      mental health services (OR = 1.91, CI = 1.11-3.27, p = .019). The influence of
      social networks on mental health service use did not differ between ethnic
      groups. CONCLUSIONS: The differential treatment of women from Pakistani and
      Bangladeshi ethnic groups in primary care settings could be a possible reason for
      the observed differences in mental health service use.

PMID- 27892691
TI  - A new sulfonylated flavonoid and other bioactive compounds isolated from the
      aerial parts of Cotula anthemoides L.
AB  - A new sulfonyl flavonol glucoside, 5,7,4',5'-tetrahydoxyflavonol 2'-[propanoic
      acid-(2"'-acetoxy-1"'-sulfonyl)]-5'-O-beta-d-glucopyranoside (1) was isolated
      from the aerial parts of Cotula anthemoides L. in addition to 15 known compounds
      (2-16). The structure elucidation of these compounds was based on analyses of
      spectroscopic data including 1D-, 2D-NMR and HR-ESI-MS techniques and by
      comparing their NMR data with those reported in the literature. These compounds
      were evaluated for their DPPH radical scavenging and tyrosinase inhibitory
      activity. Compound 6 showed a high DPPH radical scavenging with EC50 value of 9.1
      +/- 0.4 MUM. Compound 11, 9 and 1 exhibited a mild tyrosinase inhibitory activity
      with IC50 values of 85 +/- 0.8, 95 +/- 1.5 and 100 +/- 0.5 MUM, respectively.

PMID- 27892692
TI  - Changes in depression mediate the effects of AA attendance on alcohol use
      outcomes.
AB  - BACKGROUND: Depression may contribute to increased drinking in individuals with
      alcohol use disorder. Although Alcoholics Anonymous (AA) attendance predicts
      drinking reductions, there is conflicting information regarding the intermediary
      role played by reductions in depression. OBJECTIVES: We explored whether AA
      attendance reduces depressive symptoms, the degree to which improvement in
      depression results in reductions in drinking, and in which subgroups these
      effects occur. METHODS: 253 early AA affiliates (63% male) were recruited and
      assessed at baseline 3, 6, 9, 12, 18, and 24 months. Depression was measured
      using the Beck Depression Inventory (BDI) and was administered at baseline 3, 6,
      12, 18, and 24 months. AA attendance and alcohol use outcomes were obtained with
      the Form 90. Mediation analyses were performed at early (3, 6, and 9 months) and
      late (12, 18, and 24 months) follow-up to investigate the degree to which
      reductions in depression mediated the effect of AA attendance on drinking,
      controlling for concurrent drinking. In addition, a series of moderated mediation
      analyses were performed using baseline depression severity as a moderator.
      RESULTS: At early follow-up, reductions in depression (6 months) mediated the
      effects of AA attendance (3 months) on later drinking (drinks per drinking day)
      (9 months) (b = -0.02, boot CI [-0.055, -0.0004]), controlling for drinking at 6
      months. Baseline depression severity did not moderate the degree to which BDI
      mediated the effects of AA attendance on alcohol use (ps > .05). CONCLUSION:
      These findings provide further evidence that depression reduction is a mechanism
      by which AA attendance leads to reductions in alcohol use. Improving depression
      may help reduce alcohol use in individuals with AUD, and AA attendance may be an
      effective way to achieve that goal.

PMID- 27892693
TI  - A Graph Approach to Mining Biological Patterns in the Binding Interfaces.
AB  - Protein-RNA interactions play important roles in the biological systems.
      Searching for regular patterns in the Protein-RNA binding interfaces is important
      for understanding how protein and RNA recognize each other and bind to form a
      complex. Herein, we present a graph-mining method for discovering biological
      patterns in the protein-RNA interfaces. We represented known protein-RNA
      interfaces using graphs and then discovered graph patterns enriched in the
      interfaces. Comparison of the discovered graph patterns with UniProt annotations
      showed that the graph patterns had a significant overlap with residue sites that
      had been proven crucial for the RNA binding by experimental methods. Using 200
      patterns as input features, a support vector machine method was able to classify
      protein surface patches into RNA-binding sites and non-RNA-binding sites with
      84.0% accuracy and 88.9% precision. We built a simple scoring function that
      calculated the total number of the graph patterns that occurred in a protein-RNA
      interface. That scoring function was able to discriminate near-native protein-RNA
      complexes from docking decoys with a performance comparable with that of a state
      of-the-art complex scoring function. Our work also revealed possible patterns
      that might be important for binding affinity.

PMID- 27892694
TI  - Gene polymorphism profiles of drug-metabolising enzymes GSTM1, GSTT1 and GSTP1 in
      an Argentinian population.
AB  - BACKGROUND: Glutathione S-transferases (GSTs) are drug-metabolising enzymes
      involved in biotransformation of carcinogens, drugs, xenobiotics and oxygen free
      radicals. Polymorphisms of GST genes contribute to inter-individual and
      population variability in the susceptibility to environmental risk factors,
      cancer predisposition and pharmacotherapy responses. However, data about GST
      variability in Argentina are lacking. AIM: The purpose was to determine the
      prevalence of GSTM1, GSTT1 and GSTP1 polymorphisms in the general population from
      a central region of Argentina and to perform inter-population comparisons.
      SUBJECTS AND METHODS: GSTM1 and GSTT1 gene deletions and GSTP1 c.313A > G were
      genotyped by PCR assays in 609 healthy and unrelated Argentinians. RESULTS: The
      frequencies of variant genotypes in Argentinians were GSTM1-null (45%), GSTT1
      null (17%) and GSTP1-GG (11%). GSTM1-present genotype was significantly
      associated with GSTP1-AG or GSTP1-GG variants (p = 0.037; p = 0.034,
      respectively). Comparison with worldwide populations demonstrated that the GST
      distributions in Argentina are similar to those reported for Italy and Spain,
      whereas significant differences were observed regarding Asian and African
      populations (p < 0.001). CONCLUSION: This study has determined, for the first
      time, the normative profile of three pharmacogenetically relevant polymorphisms
      (GSTM1, GSTT1 and GSTP1) in the largest Argentinian cohort described to date,
      providing the basis for further epidemiological and pharmacogenetic studies in
      this country.

PMID- 27892695
TI  - Defining Low-Dimensional Projections to Guide Protein Conformational Sampling.
AB  - Exploring the conformational space of proteins is critical to characterize their
      functions. Numerous methods have been proposed to sample a protein's
      conformational space, including techniques developed in the field of robotics and
      known as sampling-based motion-planning algorithms (or sampling-based planners).
      However, these algorithms suffer from the curse of dimensionality when applied to
      large proteins. Many sampling-based planners attempt to mitigate this issue by
      keeping track of sampling density to guide conformational sampling toward
      unexplored regions of the conformational space. This is often done using low
      dimensional projections as an indirect way to reduce the dimensionality of the
      exploration problem. However, how to choose an appropriate projection and how
      much it influences the planner's performance are still poorly understood issues.
      In this article, we introduce two methodologies defining low-dimensional
      projections that can be used by sampling-based planners for protein
      conformational sampling. The first method leverages information about a protein's
      flexibility to construct projections that can efficiently guide conformational
      sampling, when expert knowledge is available. The second method builds similar
      projections automatically, without expert intervention. We evaluate the
      projections produced by both methodologies on two conformational search problems
      involving three middle-size proteins. Our experiments demonstrate that (i)
      defining projections based on expert knowledge can benefit conformational
      sampling and (ii) automatically constructing such projections is a reasonable
      alternative.

PMID- 27892696
TI  - Looking like a smoker, a smokescreen to racism? Maori perceived appearance linked
      to smoking status.
AB  - OBJECTIVES: Maori, the indigenous peoples of Aotearoa (New Zealand), continue to
      exhibit the highest rate of smoking of any ethnic group in the nation. Clarifying
      the present day factors which perpetuate Maori smoking has become matter of some
      urgency. DESIGN: We investigate links between subjective elements of Maori
      identity, demographic factors and perceived discrimination with smoking status in
      a national probability sample of self-identified Maori (N = 667). RESULTS: Our
      results suggest that core aspects of Maori identity and cultural engagement were
      not significantly linked with smoking. However, the extent to which participants
      felt they were perceived as prototypically Maori (measured as Perceived
      Appearance) was reliably associated with smoking. The effect of Perceived
      Appearance held when adjusting for perceived experiences of discrimination and
      other standard demographic indicators. CONCLUSION: Our analysis indicates that
      simply feeling that one is more visibly Maori is associated with an increased
      likelihood of smoking. This may reflect how Maori negotiate the larger systemic
      forces of racism present in New Zealand society.

PMID- 27892697
TI  - Allium Roseum L. Extract Exerts Potent Suppressive Activities on Chronic Myeloid
      Leukemia K562 Cell Viability Through the Inhibition of BCR-ABL, PI3K/Akt, and
      ERK1/2 Pathways and the Abrogation of VEGF Secretion.
AB  - Use of plant extracts, alone or combined to the current chemotherapy as
      chemosensitizers, has emerged as a promising strategy to overcome tumor drug
      resistance. Here, we investigated the anticancer activity of Allium roseum L.
      extracts, a wild edible species in North Africa, on human Chronic Myeloid
      Leukemia (CML) K562 cells. The dehydrated aqueous extract (DAE) disturbed the
      cell cycle progression and induced the apoptosis of K562 cells. Chemical analysis
      of DAE showed a diversity of organosulfur compounds S-alk(en)yl-cysteine
      sulfoxides (RCSO) and high amount of allicin, suggesting that such molecule may
      be behind its antitumor effect. DAE was efficient in inhibiting K562 cell
      viability. DAE inhibitory effect was associated with the dephosphorylation of the
      BCR-ABL kinase and interfered with ERK1/2, Akt, and STAT5 pathways. Furthermore,
      we found that DAE-induced inactivation of Akt kinase led to the activation of its
      target FOXO3 transcription factor, enhancing the expression of FOXO3-regulated
      proapoptotic effectors, Bim and Bax, and cell cycle inhibitor p27. Finally, we
      found that DAE reduced the secretion of vascular endothelial growth factor.
      Overall, our data suggest that A. roseum extract has great potential as a
      nontoxic cheap and effective alternative to conventional chemotherapy.

PMID- 27892698
TI  - The relationship between oestrogen and executive functioning in ALS females with
      emerging Frontotemporal Lobar Degeneration (FTLD) supports a neuroendocrine model
      of FTLD attenuation.
AB  - OBJECTIVE: The prevalence of ALS cognitive or behavioural impairment (ci or bi)
      consistent with Frontotemporal Degeneration (FTLD) approachs 50%, while ~5-10%
      progress to dementia. Our goal was to explore ci and bi differencs between bulbar
      and limb onset, as well as the neuroprotective potential of oestrogen in emerging
      FTLD. METHODS: We applied Mann Whitney U to evaluate differences in cognitive and
      behavioural profiles between site of onset in 78 female and 83 male non-demented
      ALS participants classified by current consensus criteria with ci. For females,
      we also examined differences by oestrogen level. FINDINGS: Between group analyses
      found significantly worse Letter Fluency (LF) for bulbar onset, and worse
      Category Fluency (CF) for bulbar females. Significantly worse performance was
      found for low oestrogen females for LF and Similarities, with significantly worse
      LF for low oestrogen bulbar onset. No significant differences were found for
      behavioural subgroups, while moderate-severe range traits were higher in
      occurrence for bulbar and low oestrogen bulbar onset. CONCLUSIONS: Findings
      support our previously published mesocortical pathway associated "bottom-up"
      model of FTLD emergence in ALSbi, extending it with a hierarchal hypothesis
      involving ascending cerebellar pathways in ALSci and ALSbi, further suggesting a
      role for oestrogen in mitigating female FTLD progression.

PMID- 27892699
TI  - Genetics of consanguinity and inbreeding in health and disease.
AB  - CONTEXT: Inbreeding increases the level of homozygotes for autosomal recessive
      disorders and is the major objective in clinical studies. The prevalence of
      consanguinity and the degree of inbreeding vary from one population to another
      depending on ethnicity, religion, culture and geography. Global epidemiological
      studies have revealed that consanguineous unions have been significantly
      associated with increased susceptibility to various forms of inherited diseases.
      OBJECTIVE: The study aimed to determine the role of consanguinity in human health
      and to highlight the associated risks for various diseases or disorders. METHODS:
      PubMed and Google Scholar search engines were used to explore the published
      literature on consanguinity and its associated risks using the key words
      "consanguinity", "prevalence", "inbreeding depression", "coefficient of
      inbreeding", "child health", "mortality", "human health", "homozygosity" and
      "complex diseases" in different combinations. The studies were screened for
      eligibility on the basis of their epidemiological relevance. RESULTS: This
      comprehensive assessment highlights the deleterious consequences in populations
      with a higher prevalence of consanguinity among different countries worldwide.
      CONCLUSIONS: To avoid the inbreeding load there is the need to improve
      socioeconomic and educational status and to increase public awareness of
      reproductive health and anticipated deleterious effects. Pre-marital and pre
      conception counselling of consanguineous populations should be an integral part
      of health policy to train people and make people aware of its harmful
      consequences. Furthermore, runs of homozygosity (ROH) and whole-exome sequencing
      (WES) are useful tools in exploring new genomic signatures for the cause of
      inbreeding depression.

PMID- 27892700
TI  - Justificatory Information Forefending in Digital Age: Self-Sealing Informational
      Conviction of Risky Health Behavior.
AB  - This study proposes the idea of justificatory information forefending, a
      cognitive process by which individuals accept information that confirms their
      preexisting health beliefs, and reject information that is dissonant with their
      attitudes. In light of the sheer volume of often contradictory information
      related to health that is frequently highlighted by the traditional media, this
      study sought to identify antecedents and outcomes of this justificatory
      information forefending. Results indicate that individuals who are exposed to
      contradictory health information, currently engage in risky health behavior, are
      comfortable using the Internet to search for information, and are currently
      taking steps to maintain their health are likely to actively select health
      information that confirms their preexisting notions about their health, and to
      reject information that is contradictory to their beliefs. Additionally,
      individuals who engage in justificatory information forefending were also found
      to continue to engage in risky health behavior. Implications for theory and
      practice are discussed.

PMID- 27892701
TI  - We-Caring: Searching for Online Health Information by Italian Families.
AB  - Using data collected by the Italian National Institute of Statistics on 19,000
      Italian adults who had accessed the Internet in 2013, our study investigates the
      interaction between online health information-seeking behaviors and family
      obligations among household members. The study presents a detailed picture of the
      likelihood of online health information searching according to health status and
      gendered family roles. Findings of binomial logistic regression models highlight
      that family obligations per se influence the probability of searching, regardless
      of the health of the seeker and that of family members. Illness, whether
      affecting the seeker or other individuals within the family network, proves to be
      another trigger for online health information seeking. Directions for future
      research and practical implications for public health organizations are
      discussed.

PMID- 27892702
TI  - Slowly progressive motor neuron disease with multi-system involvement related to
      p.E121G SOD1 mutation.
AB  - We report the third case of amyotrophic lateral sclerosis related to p.E121G
      Superoxide dismutase-1 (SOD1) mutation. Besides a sporadic presentation and a
      slow progressive course, as described in the 2 previously cases, our patient
      presented with prominent sensory and cerebellar signs. This case report
      strengthens that p.E121G should be considered as a causal mutation. Slowly upper
      and lower motor neuron degeneration, even with non-motor clinical features,
      should prompt a sequencing of SOD1.

PMID- 27892703
TI  - The measurement and estimation of total energy expenditure in Japanese patients
      with ALS: a doubly labelled water method study.
AB  - Appropriate nutritional therapy has not been established for patients with
      amyotrophic lateral sclerosis (ALS). Our objective was to measure the total
      energy expenditure (TEE) and determine an equation to estimate the energy
      requirements for Japanese patients with ALS. Twenty-six Japanese patients with
      ALS participated in the study. The TEE was measured using the doubly labelled
      water (DLW) method for a 14-day period. Using a range of clinical parameters and
      multiple regression analyses, we determined an adequate equation to calculate
      TEE. Results showed that the median value of total energy intake (TEI) was 1581
      (interquartile 1278-1782) kcal/d. TEE and TEE/body weight were 1628 kcal/d (1352
      1865) and 31.3 kcal/kg (29.2-34.4), respectively. The ratio of TEE/estimated TEE
      by the Harris-Benedict equation was 1.14 (1.09-1.26). The difference between TEI
      and TEE was -63 kcal (-221 - 122), and 15 patients (57.7%) showed a negative
      balance. From regression analyses, we determined an equation to estimate TEE
      using the resting metabolic rate estimated by the Harris-Benedict equation (RMR
      HB) and scores of the revised ALS Functional Rating Scale (ALSFRS-R): TEE = (1.67
      * RMR-HB) + (11.8 * ALSFRS-R) - 680 (p < 0.0001). In conclusion, energy
      expenditure of Japanese patients with ALS was higher than expected, and we
      proposed a preliminary equation to estimate TEE for future nutritional
      intervention.

PMID- 27892705
TI  - Modeling the degradation kinetics of ascorbic acid.
AB  - Most published reports on ascorbic acid (AA) degradation during food storage and
      heat preservation suggest that it follows first-order kinetics. Deviations from
      this pattern include Weibullian decay, and exponential drop approaching finite
      nonzero retention. Almost invariably, the degradation rate constant's temperature
      dependence followed the Arrhenius equation, and hence the simpler exponential
      model too. A formula and freely downloadable interactive Wolfram Demonstration to
      convert the Arrhenius model's energy of activation, Ea, to the exponential
      model's c parameter, or vice versa, are provided. The AA's isothermal and non
      isothermal degradation can be simulated with freely downloadable interactive
      Wolfram Demonstrations in which the model's parameters can be entered and
      modified by moving sliders on the screen. Where the degradation is known a priori
      to follow first or other fixed order kinetics, one can use the endpoints method,
      and in principle the successive points method too, to estimate the reaction's
      kinetic parameters from considerably fewer AA concentration determinations than
      in the traditional manner. Freeware to do the calculations by either method has
      been recently made available on the Internet. Once obtained in this way, the
      kinetic parameters can be used to reconstruct the entire degradation curves and
      predict those at different temperature profiles, isothermal or dynamic.
      Comparison of the predicted concentration ratios with experimental ones offers a
      way to validate or refute the kinetic model and the assumptions on which it is
      based.

PMID- 27892704
TI  - The effects of a 16-week aerobic exercise programme on cognitive function in
      people living with HIV.
AB  - High levels of cardiovascular fitness and physical activity are associated with
      higher levels of cognitive function in people with HIV, thus, they may reduce the
      risk of developing HIV-associated neurocognitive disorder (HAND). This study
      aimed to investigate the effects of a 16-week aerobic exercise intervention on
      cognitive function in people with HIV. Eleven participants living with HIV were
      recruited into the study. Participants were randomised into either an exercise
      group (n = 5), that completed a 16-week aerobic exercise programme training, 3
      times per week (2 supervised sessions and one unsupervised session) or a control
      group (n = 6) that received no intervention. Outcomes measured included cognitive
      function (Montreal cognitive assessment (MOCA) and the Trail making tests A and
      B), aerobic fitness (modified Bruce protocol), sleep quality (Pittsburgh sleep
      quality index; PSQI) and physical activity levels (seven-day accelerometry). At
      baseline, higher levels of moderate physical activity were positively correlated
      with higher MOCA scores and levels of aerobic fitness were negatively associated
      with Trail A scores (P = 0.04 and P = 0.001 respectively). However, exercise
      training did not induce any significant improvements in cognitive function or
      aerobic fitness. The overall mean adherence rate to the exercise programme was
      60%. In conclusion, in the present study a 16-week aerobic exercise intervention
      did not affect the cognitive function of participants with HIV. It is likely that
      longer intervention periods and/or higher adherence rates to exercise might be
      needed for an aerobic exercise programme to be effective in improving cognitive
      function in a cohort with no baseline cognitive impairments.

PMID- 27892706
TI  - 'If I went to my mom with that information, I'm dead': sexual health knowledge
      barriers among immigrant and refugee Somali young adults in Ohio.
AB  - OBJECTIVES: Adequate knowledge of sexual health among young adults is a critical
      step in prevention of sexually transmitted diseases and maintenance of adult
      sexual health. Knowledge of specific barriers to accessing sexual health
      knowledge can help tailor approaches appropriately. The purpose of this paper was
      to identify sexual health knowledge barriers among Somali young adults in Ohio.
      DESIGN: In-depth interviews were conducted with a convenience sample of 27 Somali
      young adults aged 18-25 years. Using a grounded theory approach, a semi
      structured interview guide comprising open-ended questions and probes was
      utilized to collect data. Data were analyzed and coded using constant comparative
      analysis. RESULTS: Findings revealed sexual health knowledge barriers in the
      following broad categories: religion, culture and stigma. Cultural and religious
      norms were deemed an important influence on the community norms largely impacting
      sexual health knowledge due to stigma and fear of judgment. Participants overcame
      barriers by seeking information from external sources such as doctors, Internet
      and peers. CONCLUSION: Study findings support an approach that will address
      sexual health barriers in the Somali immigrant young community at multiple
      levels: individual, interpersonal and community levels. A collaborative effort
      across religious, cultural and educational setting is necessary to tailor
      approaches that meet the needs of the priority group.

PMID- 27892707
TI  - Is firstly diagnosed ALS really ALS? Results of a population-based study with
      long-term follow-up.
AB  - OBJECTIVE: To revise the first diagnosis of amyotrophic lateral sclerosis (ALS)
      in patients from a well-defined population. METHODS: Patients diagnosed with ALS
      in the years 1998-2002 and resident of Lombardy Region, Northern Italy were
      followed until death or April 30 2016 to assess long-term survival. During follow
      up, the caring neurologists were asked to confirm the first diagnosis. Revised
      diagnoses were classified as confirmed and unconfirmed motor neuron disease (MND)
      with further specification where available. The two groups were compared for age,
      sex, disease duration at diagnosis, site of onset, and El Escorial category.
      Survival with predictors were also compared. RESULTS: Included were 280 men and
      203 women aged 18-93 years. During follow-up, 25 cases (5.2%) received a
      diagnosis different from MND. Diseases of spinal roots and peripheral nerves and
      vascular encephalopathy predominated. Patients with definite (OR 0.15; 95%CI 0.04
      0.52) and probable (OR 0.15; 95%CI 0.04-0.62) ALS were least likely to have an
      unconfirmed MND diagnosis. At end of follow-up, 2.2% of patients with confirmed
      MND and 44.0% of patients with unconfirmed MND were reported alive (HR 0.14;
      95%CI 0.08-0.25). CONCLUSIONS: At the time of a first diagnosis of ALS, the
      possibility still exists that another, less severe clinical condition, is
      present.

PMID- 27892708
TI  - Antitumoral Effects of D-Fraction from Grifola Frondosa (Maitake) Mushroom in
      Breast Cancer.
AB  - D-Fraction is protein-bound beta-1,6 and beta-1,3 glucans (proteoglucan)
      extracted from the edible and medicinal mushroom Grifola frondosa (Maitake). The
      antitumoral effect of D-Fraction has long been exclusively attributed to their
      immunostimulatory capacity. However, in recent years increasing evidence showed
      that D-Fraction directly affects the viability of canine and human tumor cells,
      independent of the immune system. Previously, we have reported that D-Fraction
      modulates the expression of genes associated with cell proliferation, cell death,
      migration, invasion, and metastasis in MCF7 human breast cancer cells. Therefore,
      the purpose of the current study is to investigate if this modulation of gene
      expression by Maitake D-Fraction really modulates tumor progression. In the
      present work, we demonstrate for the first time that Maitake D-Fraction is able
      to act directly on mammary tumor cells, modulating different cellular processes
      involved in the development and progression of cancer. We demonstrate that D
      Fraction decreases cell viability, increases cell adhesion, and reduces the
      migration and invasion of mammary tumor cells, generating a less aggressive cell
      behavior. In concordance with these results, we also demonstrate that D-Fraction
      decreases tumor burden and the number of lung metastases in a murine model of
      breast cancer.

PMID- 27892709
TI  - Gut-borne Saccharomyces cerevisiae, a promising candidate for the formulation of
      feed additives, modulates immune system and gut microbiota.
AB  - The aim was to evaluate the effect of Saccharomyces cerevisiae RC016 on immune
      parameters and gut microbiota in healthy mice. Animals received S. cerevisiae
      RC016 for 10 days. Microbial translocation to liver and changes in some bacterial
      populations in caecum were determined. Immune stimulation was assessed at gut
      level (measure ofimmunoglobulin A (IgA)+ cells and luminal cytokine profile) and
      by evaluating the activity of peritoneal macrophages. Oral administration of S.
      cerevisiae RC016 did not induce microbial translocation to liver. Mice that
      received yeast increased the number of IgA+ cells in their intestines, the
      phagocytic activity of peritoneal macrophages and decreased tumour necrosis
      factor alpha (TNF-alpha) levels in the small intestine with increases of
      interleukin-10/TNF-alpharatio. Administration of S. cerevisiae RC016 caused the
      decline of a logarithmic unit for Enterobacteriaceae counts compared to the
      control. The immune and gut microbiota modulation observed demonstrates that S.
      cerevisiae RC016 is a promising candidate for the formulation of feed additives
      to improve animal productivity. The beneficial in vivo effects observed for the
      potential probiotic S. cerevisiae RC016 with previously reported mycotoxin
      bindingproperties, demonstrated that this strain could be suitable to be included
      in a novel product to improve animalproductivity, with both probiotic and
      mycotoxin-binding properties. However, studies in the specific host will be
      necessary to confirm this potential.

PMID- 27892710
TI  - Oxytocin, a missing link of the gut-brain axis between probiotics and chronic
      migraine?Comment on 'The effects of the multispecies probiotic mixture
      Ecologic(r)Barrier on migraine:results of an open-label pilot study'.

PMID- 27892711
TI  - Clinical indicators associated with HIV acquisition in the United States Air
      Force.
AB  - Mandatory HIV screening of United States Air Force (USAF) personnel every two
      years effectively identifies incident cases, however testing frequency limits the
      ability to detect early HIV infection. Identifying clinical indicators of HIV in
      the USAF population is necessary to develop a supplemental provider-based
      targeted testing strategy. We conducted a matched case-control study of male
      active duty USAF personnel with a new HIV diagnosis (n = 452) between 1996 and
      2011 matched to five randomly selected controls (n = 2176). The relationship
      between clinical diagnoses, determined by ICD-9 codes, and HIV infection was
      assessed using conditional logistic regression. In unadjusted analyses of ICD-9
      codes ever and within the last two years before HIV diagnosis, the conditional
      odds of HIV infection were greater in those with clinical signs and symptoms of
      HIV (cOR 5.05, 95% CI 4.00-6.39), mental health diagnoses (cOR 2.61, 95% CI 1.86
      3.67), and STI diagnoses (cOR 2.33, 95% CI 1.50-3.60). Compared to those with
      <=10 medical encounters in the two years prior to HIV diagnosis, individuals with
      11-35 medical encounters (cOR 2.19, 95% CI 1.73-2.79) and >35 medical encounters
      (cOR 4.15, 95% CI 2.69-6.39) had a higher odds of HIV acquisition. In
      multivariate analyses, clinical signs and symptoms of HIV within the last two
      years of HIV diagnosis (cOR 4.10, 95% CI 3.22-5.22) and ever having a mental
      health diagnosis (cOR 1.97, 95% CI 1.44-2.70) remained significant (p < .01).
      Clinical encounters, particularly those featuring clinical signs and symptoms of
      HIV or a history of mental health complaints, provide an opportunity for targeted
      testing as a supplement to mandated testing at two-year intervals. Provider
      education to increase HIV testing in persons at risk would enhance early HIV
      diagnosis and potentially reduce forward transmission in the USAF population.

PMID- 27892712
TI  - Variability in Metagenomic Count Data and Its Influence on the Identification of
      Differentially Abundant Genes.
AB  - Metagenomics is the study of microorganisms in environmental and clinical samples
      using high-throughput sequencing of random fragments of their DNA. Since
      metagenomics does not require any prior culturing of isolates, entire microbial
      communities can be studied directly in their natural state. In metagenomics, the
      abundance of genes is quantified by sorting and counting the DNA fragments. The
      resulting count data are high-dimensional and affected by high levels of
      technical and biological noise that make the statistical analysis challenging. In
      this article, we introduce an hierarchical overdispersed Poisson model to explore
      the variability in metagenomic data. By analyzing three comprehensive data sets,
      we show that the gene-specific variability varies substantially between genes and
      is dependent on biological function. We also assess the power of identifying
      differentially abundant genes and show that incorrect assumptions about the gene
      specific variability can lead to unacceptable high rates of false positives.
      Finally, we evaluate shrinkage approaches to improve the variance estimation and
      show that the prior choice significantly affects the statistical power. The
      results presented in this study further elucidate the complex variance structure
      of metagenomic data and provide suggestions for accurate and reliable
      identification of differentially abundant genes.

PMID- 27892713
TI  - Hydrophobic ion pairing as a strategy to improve drug encapsulation into lipid
      nanocarriers for the cancer treatment.
AB  - INTRODUCTION: Incorporation of anticancer drugs with low lipophilicity in lipid
      nanocarriers is usually low, which limits the utilization of this strategy in
      cancer therapy. However, the complexation of these drugs with lipophilic ion
      pairs containing ionizable groups has been reported to improve their
      incorporation in nanocarriers such as solid lipid nanoparticles (SLNs),
      nanostructured lipid nanocarriers (NLCs), and nanoemulsions (NEs). Therefore,
      those nanocarriers have shown an increase in efficacy and lower toxicity compared
      with the free drugs, particularly if the counter ion utilized has anticancer
      activity. Areas covered: This review covers, from 1999 to the present, the
      utilization of the hydrophobic ion pair (HIP) approach to enhance the
      encapsulation of anticancer drugs in lipid nanostructured delivery systems, SLN,
      NLC, and NE; the benefits achieved; and challenges to improve the anticancer
      therapy. Expert opinion: The HIP strategy has consistently demonstrated
      enhancement of the encapsulation efficiency in NLCs associated with increased
      anticancer activity of drugs such as doxorubicin, all-trans retinoic acid,
      methotrexate, vincristine and others. From this point on, conducting further
      physicochemical characterization studies of the formed ion pair as well as
      proceeding with the in vivo efficacy, toxicity and pharmacokinetics studies are
      expected.

PMID- 27892714
TI  - (2R, 3S)-Pinobanksin-3-cinnamate ameliorates photoreceptor degeneration in
      Pde6rd10 mice.
AB  - As an inherited disorder caused by initial death of rod photoreceptors, retinitis
      pigmentosa is currently untreatable and usually leads to partial or complete
      blindness. (2R, 3S)-Pinobanksin-3-cinnamate (PC) is a new flavonone isolated from
      the seed of Alpinia galanga Willd, and has been reported to exert neuroprotective
      effects by upregulating endogenous antioxidant enzymes. In this study, the anti
      oxidative and neuroprotective activity of PC against photoreceptor apoptosis in
      rd10 mouse model of retinitis pigmentosa was explored. PC showed to produce
      significant improvement in histology and function in rd10 mice through reducing
      oxidative stress. For the first time, the protective effects of PC were
      demonstrated against retina degeneration in rd10 mice and our study provides
      scientific rationale on using PC as the supplementary treatment to the outer
      retina diseases, including retinitis pigmentosa, in which oxidative stress is
      thought to contribute to disease progression.

PMID- 27892716
TI  - Life and cancer without telomerase: ALT and other strategies for making sure ends
      (don't) meet.
AB  - While most cancer cells rely on telomerase expression/re-activation for linear
      chromosome maintenance and sustained proliferation, a significant population of
      cancers (10-15%) employs telomerase-independent strategies, collectively dubbed
      Alternative Lengthening of Telomeres (ALT). Most ALT cells relax the usual role
      of telomeres as inhibitors of local homologous recombination while maintaining
      the ability of telomeres to prohibit local non-homologous end joining reactions.
      Here we review current concepts surrounding how ALT telomeres achieve this new
      balance via alterations in chromatin landscape, DNA damage repair processes and
      handling of telomeric transcription. We also discuss telomerase independent end
      maintenance strategies utilized by other organisms, including fruitflies and
      yeasts, to draw parallels and contrasts and highlight additional modes, beyond
      ALT, that may be available to telomerase-minus cancers. We conclude by commenting
      on promises and challenges in the development of effective anti-ALT cancer
      therapies.

PMID- 27892718
TI  - The utility of DNA nanostructures for drug delivery in vivo.

PMID- 27892717
TI  - Dental implants modified with drug releasing titania nanotubes: therapeutic
      potential and developmental challenges.
AB  - INTRODUCTION: The transmucosal nature of dental implants presents a unique
      therapeutic challenge, requiring not only rapid establishment and subsequent
      maintenance of osseointegration, but also the formation of resilient soft tissue
      integration. Key challenges in achieving long-term success are sub-optimal bone
      integration in compromised bone conditions and impaired trans-mucosal tissue
      integration in the presence of a persistent oral microbial biofilm. These
      challenges can be targeted by employing a drug-releasing implant modification
      such as TiO2 nanotubes (TNTs), engineered on titanium surfaces via
      electrochemical anodization. Areas covered: This review focuses on applications
      of TNT-based dental implants towards achieving optimal therapeutic efficacy.
      Firstly, the functions of TNT implants will be explored in terms of their
      influence on osseointegration, soft tissue integration and immunomodulation.
      Secondly, the developmental challenges associated with such implants are reviewed
      including sterilization, stability and toxicity. Expert opinion: The potential of
      TNTs is yet to be fully explored in the context of the complex oral environment,
      including appropriate modulation of alveolar bone healing, immune-inflammatory
      processes, and soft tissue responses. Besides long-term in vivo assessment under
      masticatory loading conditions, investigating drug-release profiles in vivo and
      addressing various technical challenges are required to bridge the gap between
      research and clinical dentistry.

PMID- 27892715
TI  - Incorporation of chemotherapeutic agent and photosensitizer in a low temperature
      sensitive liposome for effective chemo-hyperthermic anticancer activity.
AB  - OBJECTIVES: In this study, we combined chemo- and hyperthermia therapy in a low
      temperature-sensitive liposome (LTSL) for potential cancer treatment. METHODS:
      Docetaxel (DOC) and indocyanine green (ICG) as a therapeutic agent and
      photosensitizer, respectively, were incorporated in a low temperature-sensitive
      liposome (LTSL/DI). Nanoparticles were evaluated for the physicochemical
      characterizations, in vitro uptake and cytotoxicity, and furthermore in vivo
      anticancer activity. RESULTS: The particle size of LTSL/DI was 130.8 +/- 2.3 nm,
      and its drug release profile was pH- and temperature-dependent, which are
      effective for tumor targeting. The in vitro anticancer activity of LTSL/DI was
      significantly enhanced compared with free DOC in SCC-7 and MCF-7 cell lines.
      Interestingly, near-infrared laser irradiation after the treatment resulted in
      better anticancer activity than in the non-irradiated condition. The in vivo
      tumor regression effect of LTSL/DI in combination with NIR irradiation was much
      greater compared with the control group in SCC-7 tumor-bearing mice. After
      intratumoral injection of LTSL/DI, local heat induced by NIR irradiation and the
      localized docetaxel burst release could completely ablate the tumor, and inhibit
      its recurrence. CONCLUSIONS: These results suggest LTSL/DI formulation as a
      potential therapeutic strategy with effectively localized anti-tumor activity and
      low risk of side effect to non-target organs.

PMID- 27892719
TI  - Is a pulse absolutely necessary during cardiopulmonary bypass?
AB  - INTRODUCTION: The benefits and disadvantages of pulsatility in mechanical
      circulatory support devices have been argued since before the first use of
      cardiopulmonary bypass (CPB) with a nonpulsatile pump. The debate over the
      superiority of either pulsatile or nonpulsatile perfusion during CPB persists,
      but recently, the evidence in favor of pulsatile perfusion during CPB is
      increasing. Complications associated with chronic nonpulsatile flow in patients
      implanted with left ventricular assist devices have renewed interest in
      generating pulsatility with these devices. Areas covered: Here we review the
      definition of pulsatility, the outcomes of CPB using pulsatile and nonpulsatile
      pumps, and how best to produce and assess pulsatility. This information was
      identified through online databases and direct extraction of single studies cited
      in previously identified reports. Expert commentary: The newer generation of
      biocompatible pulsatile pumps that can generate physiologic pulsation may prove
      beneficial during temporary support for short-term use during CPB or intermediate
      support for cardiogenic shock.

PMID- 27892721
TI  - Social aspects in additive manufacturing of pharmaceutical products.
AB  - INTRODUCTION: Additive manufacturing (AM) techniques, such as drug printing,
      represent a new engineering approach that can implement the concept of
      personalized medicine via on-demand manufacturing of dosage forms with
      individually adjusted doses. Implementation of AM principles, such as
      pharmacoprinting, will challenge the entire drug distribution chain and affect
      the society at different levels. Areas covered: This work summarizes the concept
      of personalized medicine and gives an overview of possibilities for monitoring
      patients' health. The most recent activities in the field of printing
      technologies for fabrication of dosage forms and 'polypills' with flexible doses
      and tailored release profiles are reviewed. Different scenarios for the drug
      distribution chain with the required adjustments in drug logistics, quality
      systems and environmental safety are discussed, as well as whether AM will be
      used for production of on-demand medicine. The impact of such changes in the
      distribution chain on regulation, healthcare professionals and patients are
      highlighted. Expert opinion: Drug manufacturing by traditional methods is well
      established, but it lacks the possibility for on-demand personalized drug
      production. With the recent approval of the first printed medicine, society
      should be prepared for the changes that will follow the introduction of printed
      pharmaceuticals.

PMID- 27892720
TI  - Association between chronic pancreatitis and pyogenic liver abscess: a nationwide
      population study.
AB  - BACKGROUND: The relationship between chronic pancreatitis (CP) and subsequent
      pyogenic liver abscess (PLA) is not well understood. METHODS: We investigated the
      risk of PLA in patients with CP using inpatient claims data from the Taiwan
      National Health Insurance Program for the period 2000-2010. We identified 17,810
      patients with chronic pancreatitis (CP group) and 71,240 patients without CP (non
      CP group). Both cohorts were followed until a diagnosis of PLA, until they were
      censored from the study because of loss to follow-up, death, or termination of
      insurance, or until the study cut-off date of 31 December 2011. Incidence and
      risk factors for development of PLA, and the effects of comorbidities, were
      assessed. RESULTS: The incidence of PLA in the CP group was 12.9 times that in
      the non-CP group (38.3 vs. 2.89 events per 1000 person-years; 95% confidence
      interval [CI], 10.5-15.8). After adjusting for age, sex, and the comorbidities of
      hypertension, diabetes, hyperlipidemia, cerebral vascular accident, cirrhosis,
      heart failure, chronic obstructive pulmonary disease, chronic kidney disease,
      cancer, alcoholism, other diseases of the pancreas, cholecystitis, and
      cholelithiasis and other disorders of the biliary tract and endoscopic insertion
      of stent (tube) into the bile duct, the risk of PLA remained higher among CP
      patients than among the comparison cohort (adjusted hazard ratio, 6.40; 95% CI,
      4.83-8.49). CP patients with five or more comorbidities had a significantly
      higher risk of PLA (adjusted hazard ratio, 24.9; 95% CI, 18.3-33.8). CONCLUSION:
      CP was associated with increased risk of subsequent PLA. The risk of PLA was
      higher in patients with five or more comorbidities.

PMID- 27892722
TI  - Present and future DNA vaccines for chronic hepatitis B treatment.
AB  - INTRODUCTION: With at least 240 million hepatitis B virus (HBV) carriers
      worldwide, being at a high risk of cirrhosis and hepatocellular carcinoma (HCC),
      chronic hepatitis B remains a major public health issue. Because current
      antiviral treatments are only virostatic, there is an urgent need for the
      development of innovative anti-HBV strategies leading to the functional cure. In
      this context, DNA-based vaccines appear as a promising approach. Area covered: In
      this review, the authors summarize the pertinent features of DNA vaccines for
      chronic hepatitis B therapy. They review several technologies that improve DNA
      vaccines efficacy evaluated in animal models of hepadnaviral infection. They also
      discuss the clinical trials of therapeutic DNA vaccination initiated in HBV
      carrier patients. Expert opinion: Preclinical studies in HBV transgenic mice,
      DHBV-carrier ducks and WHV-infected woodchucks, have clearly demonstrated a
      benefit of DNA vaccine-based combination therapies for chronic hepatitis B
      treatment. However, the results of clinical trials conducted in HBV patients were
      rather disappointing and frustrating, as DNA-vaccines have not shown the same
      efficacy in patients as in animal models. We are convinced that the design of
      innovative clinical trials based on strategies able to increase DNA vaccine
      immunogenicity will allow to advance in this challenging field.

PMID- 27892723
TI  - Optimization and stratification of multiple sclerosis treatment in fast
      developing economic countries: a perspective from Qatar.
AB  - OBJECTIVE: The introduction of disease-modifying therapies (DMTs) - with varying
      degrees of efficacy for reducing annual relapse rate and disability progression -
      has considerably transformed the therapeutic landscape of relapsing-remitting
      multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment
      recommendations and algorithms for the management of clinically isolated syndrome
      (CIS) and RRMS that conform to the healthcare system in a fast-developing
      economic country such as Qatar. RESEARCH DESIGN AND METHODS: We conducted a
      systematic review using a comprehensive search of MEDLINE, PubMed, and Cochrane
      Database of Systematic Reviews (1 January 1990 through 30 September 2016).
      Additional searches of the American Academy of Neurology and European Committee
      for Treatment and Research in Multiple Sclerosis abstracts from 2012 through 2016
      were performed, in addition to searches of the Food and Drug Administration and
      European Medicines Agency websites to obtain relevant safety information on these
      DMTs. RESULTS: For each of the DMTs, the mode of action, efficacy, safety and
      tolerability are briefly discussed. To facilitate the interpretation, the
      efficacy data of the pivotal phase III trials are expressed by their most
      clinically useful measure of therapeutic efficacy, the number needed to treat
      (NNT). In addition, an overview of head-to-head trials in RRMS is provided as
      well as a summary of the several different RRMS management strategies (lateral
      switching, escalation, induction, maintenance and combination therapy) and the
      potential role of each DMT. Finally, algorithms were developed for CIS, active
      and highly active or rapidly evolving RRMS and subsequent breakthrough disease or
      suboptimal treatment response while on DMTs. The benefit-to-risk profiles of the
      DMTs, taking into account patient preference, allowed the provision of rational
      and safe patient-tailored treatment algorithms. CONCLUSIONS: Recommendations and
      algorithms for the management of CIS and RRMS have been developed relevant to the
      healthcare system of this fast-developing economic country.

PMID- 27892724
TI  - Efficacy, safety and mechanism of HP-beta-CD-PEI polymers as absorption enhancers
      on the intestinal absorption of poorly absorbable drugs in rats.
AB  - CONTEXT: Oral bioavailability of some hydrophilic therapeutic macromolecules was
      very poor, thus leading to their limited application in clinic. OBJECTIVE: To
      investigate the efficacy, safety and mechanism of HP-beta-CD-PEI polymers on the
      intestinal absorption of some poorly absorbable drugs in rats. METHODS: Effects
      of HP-beta-CD-PEI polymers on the intestinal absorptions of drugs were
      investigated by an in situ closed loop method in rats. The safety of HP-beta-CD
      PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity
      and amount of protein released from rat intestinal perfusate. The absorption
      enhancing mechanisms were explored by the measurement of zeta potential,
      transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a
      paracellular marker) across rat intestinal membranes, respectively. RESULTS: HP
      beta-CD-PEI polymers, especially HP-beta-CD-PEI1800, demonstrated excellent
      absorption enhancing effects on drug absorption in a concentration-dependent
      manner and the enhancing effect was more efficient in the small intestine than
      that in the large intestine. Five percent (w/v) HP-beta-CD-PEI1800 obviously
      decreased the TEER, accompanied with increase in the intestinal transport of FD4,
      indicating that absorption enhancing actions of HP-beta-CD-PEI polymers were
      possibly performed by loosening tight junctions of intestinal epithelium cells,
      thereby increasing drug permeation via a paracellular pathway. A good liner
      relationship between absorption enhancing effects of HP-beta-CD-PEI polymers and
      their zeta potentials suggested the contribution of positive charge on the
      surface of these polymers to their absorption enhancing effects. CONCLUSION: HP
      beta-CD-PEI polymers might be potential and safe absorption enhancers for
      improving oral delivery of poorly absorbable macromolecules including peptides
      and proteins.

PMID- 27892725
TI  - Investigational serine/threonine kinase inhibitors against prostate cancer
      metastases.
AB  - INTRODUCTION: Androgen deprivation therapy (ADT) is used as first therapeutic
      approach in prostate cancer (PCa) although castration resistant disease (CRPC)
      develops with high frequency. CRPC is the consequence of lack of apoptotic
      responses to ADT. Alternative targeting of the androgen axis with abiraterone and
      enzalutamide, as well as taxane-based chemotherapy were used in CRPC.
      Serine/threonine protein kinases (STKs) regulate different molecular pathways of
      normal and neoplastic cells and participate to development of CRPC as well as to
      the progression towards a bone metastatic disease (mCRPC). Areas covered: The
      present review provide data on STK expression and activity in the development of
      CRPC as well as summarize recent reports of different strategies to block STK
      activity for the control of PCa progression. Expert Opinion: Inhibitors for
      different STKs have been developed but clinical trials in PCa are comparatively
      rare and few exhibit satisfactory 'drug-like' properties. It is, however,
      necessary to intensify, when possible, the number of clinical trials with these
      drugs in order to insert new therapies or combinations with standard hormone- and
      chemo-therapies in the treatment guidelines of the mPCA.

PMID- 27892726
TI  - Design and characterization of neurodurable gellan-xanthan pH-responsive
      hydrogels for controlled drug delivery.
AB  - OBJECTIVES: The purpose of this study was to develop novel, porous neurodurable
      interpenetrating networks of gellan-xanthan hydrogel conduits intercalated with
      pristine polymethyl methacrylate (PMMA) particles for the sustained and
      concurrent release of two model compounds: bovine serum albumin (BSA) and
      diclofenac sodium. METHODS: Hydrogel conduits were synthesized using a thermal
      ionic crosslinking mechanism with direct incorporation of PMMA. The 15
      formulations, generated using a Box-Behnken experimental design, were analyzed
      for drug release, swelling, erosion and textural properties. RESULTS: The 15
      formulations provided a near zero-order release of BSA (37-75% fractional
      release) and diclofenac sodium (14-22% fractional release) over 20 and 30 days,
      respectively, modulated via a combination of pH-responsive (pH 7.4) dissolution
      of the intercalated pristine polymer particles and the unique gelling and erosion
      properties imparted by the graded addition of xanthan gum to the hydrogel blend.
      The concentration-dependent intercalation of PMMA extended drug release rates and
      enhanced matrix resilience from 31% to 56%. CONCLUSIONS: The gellan-xanthan ratio
      variability and the pore-inducing effects of intercalated PMMA yielded a means
      for fine tuning the mechanical attributes of the hydrogel matrices, particularly
      matrix rigidity and flexibility, offering an appealing strategy for the design
      and development of synthetic bioactive-releasing peripheral nerve repair
      conduits.

PMID- 27892727
TI  - Information Deficits and Second Opinion Seeking - A Survey on Cancer Patients.
AB  - OBJECTIVE: To learn more about cancer patients' motivation for seeking a second
      opinion. METHODS: Participants filled in a standardized questionnaire. RESULTS:
      Among 106 patients, 34% had looked for a second opinion, 81% wanted to check the
      accuracy of their treatment, and 49% needed to better understand the diagnosis.
      Low understanding of information was associated with looking for a second
      opinion, and 79% felt assured after a second opinion. CONCLUSIONS: Seeking a
      second opinion may help cancer patients in coping with the disease. As data on
      benefits are missing, other strategies, such as qualified first opinion and a
      sound physician-patient communication, may be advisable.

PMID- 27892728
TI  - A Phase I/II Study of Nab-Paclitaxel, Cisplatin, and Cetuximab With Concurrent
      Radiation Therapy for Locally Advanced Squamous Cell Cancer of the Head and Neck.
AB  - Nab-paclitaxel might impact efficacy of radiation for head and neck (H&N) cancer.
      Nab-paclitaxel, cisplatin, cetuximab, and radiation were evaluated in patients
      with locally advanced head and neck cancer in this phase I/II trial. Median
      follow-up was 24 months for 34 patients. The maximum tolerated dose of nab
      paclitaxel was 20 mg/m2 with 20 mg/m2 cisplatin and 250 mg/m2 cetuximab. The 2
      year progression-free survival (PFS) was 60% (95% confidence interval (CI) 0.42,
      0.78), local control 71% (95% CI 0.55, 0.87), and overall survival 68% (95% CI
      0.50, 0.86). This is the first study evaluating these agents with radiation in
      humans, with similar 2-year PFS as historic control.

PMID- 27892729
TI  - Reduction and fragmentation of elastic fibers in the skin of obese mice is
      associated with altered mRNA expression levels of fibrillin-1 and neprilysin.
AB  - AIM OF THE STUDY: Our previous research suggested that obesity induces structural
      fragility in the skin. Elastic fibers impart strength and elasticity. In this
      study, we determined whether elastic fibers decrease in the skin of obese mice.
      MATERIALS AND METHODS: To confirm alterations in elastic fiber content due to
      obesity, we used spontaneously obese model mice (TSOD) and control mice (TSNO).
      Furthermore, to evaluate the elastin structure and gene expression dependent on
      the severity of obesity, an obesity-enhanced mouse model was developed by feeding
      a high fat diet to TSOD (TSOD-HF). Back skin samples were stained with
      hematoxylin and eosin and Elastica van Gieson for microscopic examination, and
      the samples were stained for immunohistochemical analysis of neprilysin. Gene
      expression levels were determined using a real-time PCR system. RESULTS: The
      abundance of elastic fibers beneath the epidermis was remarkably reduced and
      fragmented in TSOD as compared with TSNO. Fibrillin-1 mRNA levels in TSOD were
      significantly suppressed compared with those in TSNO, whereas neprilysin mRNA
      levels and immunohistochemical expression in TSOD were significantly increased,
      as compared with those in TSNO. The reduction of elastic fibers was enhanced and
      the expression levels of elastic fiber formed factors were significantly
      suppressed in TSOD-HF, as compared with those in the TSOD. CONCLUSIONS: The
      abundance of elastic fibers was reduced and fragmented in obesity, suggesting
      that the reduction in elastic fibers is initially caused by increased neprilysin
      and decreased fibrillin-1 expression, which may inhibit formation and
      stabilization of elastic fibers, resulting in skin fragility in obesity.

PMID- 27892730
TI  - Delivery of therapeutic RNA-cleaving oligodeoxyribonucleotides (deoxyribozymes):
      from cell culture studies to clinical trials.
AB  - INTRODUCTION: Development of efficient in vivo delivery systems remains a major
      challenge en route to clinical application of antisense technology, including RNA
      cleaving molecules such as deoxyribozymes (DNAzymes). The mechanisms of
      oligonucleotide uptake and trafficking are clearly dependent on cell type and the
      type of oligonucleotide analogue. It appears likely that each particular disease
      target would pose its own specific requirements for a delivery method. Areas
      covered. In this review we will discuss the available options for DNAzyme
      delivery in vitro and in vivo, outline various exogenous and endogenous
      strategies that have been, or are still being, developed and ascertain their
      applicability with emphasis on those methods that are currently being used in
      clinical trials. Expert opinion. The available information suggests that a
      practical system for in vivo delivery has to be biodegradable, as to minimize
      concerns over long-term toxicity, it should not accumulate in the organism.
      Extracellular vesicles may offer the most organic way for drug delivery
      especially as they can be fused with artificial liposomes to produce hybrid
      nanoparticles. Chemical modification of DNAzymes holds great potential to apply
      oligonucleotide analogs that would not only be resistant to nuclease digestion,
      but also able to penetrate cells without external delivery agents.

PMID- 27892731
TI  - Is arachidonic acid stimulation really a test for the response to aspirin? Time
      to think again?
AB  - INTRODUCTION: Platelets play a key role in pathogenesis of atherothrombosis.
      Activated platelets initiate thrombus formation. Antiplatelet therapy (APT)
      modifies these properties. APT involves aspirin. The existence of 'aspirin
      resistance' is reported in many populations with cardiovascular disease. The
      prevalence of this phenomenon is highly variable, affecting more than 50% of
      patient subgroups in some papers. Areas covered: This review describes the
      prevalence of 'aspirin resistance', analyses why there is so much apparent
      variation and addresses whether the commonly used tests of aspirin response are
      in fact accurately assessing its functional performance. The clinical
      consequences if arachidonic acid(AA)-mediated assays do not accurately assess the
      functional performance of aspirin could be important. Expert commentary: Two
      important issues arise, firstly, that it can no longer be considered robust to
      use AA-induced platelet activation as a true diagnostic test of functional
      response to aspirin. It is clear that the output from PFT using AA as an agonist
      are not even a surrogate for the pharmacological activity of aspirin. Secondly,
      current data raise important and clinically relevant questions about, how AA
      stimulation induces clotting in individuals in whom aspirin is effective at its
      COX-1 target. The evidence indicates at least one recruitable, COX-1-independent
      pathway that is associated with vascular inflammation.

PMID- 27892732
TI  - Recent advances in the management of pericardial diseases.
AB  - Pericardial diseases are relatively common in clinical practice either as
      isolated diseases or part of an underlying or systemic disease. Recent advances
      in the diagnosis and treatment have greatly improved the clinical management and
      lead to consensus documents on multimodality imaging and new guidelines on the
      diagnosis and therapy of pericardial diseases. The aim of the present paper is to
      summarize available evidence in order to provide an updated and comprehensive
      review on the recent advances in the management of pericardial diseases.

PMID- 27892733
TI  - Mean platelet volume may have not a predictive value for placental invasion
      anomalies.

PMID- 27892734
TI  - Molecular diagnosis of tuberculosis: we need solutions that span the healthcare
      value chain.

PMID- 27892735
TI  - Delivery route determines the presence of immune complexes on umbilical cord
      erythrocytes.
AB  - OBJECTIVE: Umbilical cord blood offers a unique opportunity to study the basal
      level of immunoglobulin complexes. This study aims to determine the presence of
      immune complexes and complement deposition on erythrocytes from umbilical cord
      blood from normal, full-term pregnancies. METHODS: In vitro pre-formed IgA, IgG,
      and IgM complexes were used as positive control for flow cytometry detection, and
      for C3d deposition. Blood samples (34) of umbilical cord blood taken from vaginal
      and cesarean deliveries were tested for the presence of immunoglobulin complexes.
      RESULTS: Fourteen samples from vaginal deliveries and 20 samples from cesarean
      deliveries were assessed. IgG and IgM complexes were detected on erythrocytes,
      whereas no IgA complexes or complement deposition was observed. Interestingly,
      the percentage of IgG complexes was higher on erythrocytes from vaginal delivery
      samples compared to those from cesarean deliveries. No other associations between
      immune complexes and other maternal or newborn variables were found. CONCLUSIONS:
      IgG and IgM complexes seem to be normally present on umbilical cord erythrocytes.
      Erythrocytes from vaginal deliveries have a higher percentage of IgG complexes
      present compared to that from cesarean deliveries. Since no C3d activity was
      detected, these complexes are non-pathological and should be part of the
      newborn's initial innate immune response.

PMID- 27892736
TI  - Therapeutics of postpartum depression.
AB  - INTRODUCTION: Postpartum depression is a prevalent disorder affecting many women
      of reproductive age. Despite increasing public awareness, it is frequently
      underdiagnosed and undertreated leading to significant maternal morbidity and
      adverse child outcomes. When identified, postpartum depression is usually treated
      as major depressive disorder. Many studies have identified the postpartum as a
      period of high risk for first presentations and relapses of bipolar disorder.
      Areas covered: This article reviews the acute and prophylactic treatment of
      postpartum major depressive disorder, bipolar depression and major depressive
      disorder with mixed features. The safety of antidepressant and mood stabilizing
      medications in pregnancy and breastfeeding will also be reviewed. Expert
      commentary: Differentiating postpartum major depressive disorder and postpartum
      bipolar depression can be difficult given their clinical similarities but
      accurate identification is vital for initiating proper treatment. Antidepressants
      are the mainstay of drug treatment for postpartum major depressive disorder, yet
      randomized controlled trials have shown conflicting results. A paucity of
      evidence exists for the effectiveness of antidepressant prophylaxis in the
      prevention of recurrences of major depressive disorder. Mood stabilizing
      medications reduce the risk of postpartum bipolar depression relapse but no
      randomized controlled trials have examined their use in the acute or prophylactic
      treatment of postpartum bipolar depression.

PMID- 27892737
TI  - Progress in the molecular diagnosis of Lyme disease.
AB  - INTRODUCTION: Current laboratory testing of Lyme borreliosis mostly relies on
      serological methods with known limitations. Diagnostic modalities enabling direct
      detection of pathogen at the onset of the clinical signs could overcome some of
      the limitations. Molecular methods detecting borrelial DNA seem to be the ideal
      solution, although there are some aspects that need to be considered. Areas
      covered: This review represent summary and discussion of the published data
      obtained from literature searches from PubMed and The National Library of
      Medicine (USA) together with our own experience on molecular diagnosis of Lyme
      disease. Expert commentary: Molecular methods are promising and currently serve
      as supporting diagnostic testing in Lyme borreliosis. Since the field of
      molecular diagnostics is under rapid development, molecular testing could become
      an important diagnostic modality.

PMID- 27892738
TI  - Methodological approaches and insights on protein aggregation in biological
      systems.
AB  - INTRODUCTION: The proper folding of native proteins is critical and dynamic, but
      inherently unstable. Therefore, proteins eventually end up adopting misfolded
      conformations which compromise their function and may even trigger aggregation.
      Risk factors for neurodegenerative, metabolic and heart diseases compromise
      cellular protein quality-control systems, promoting protein aggregation. Multiple
      protein post-translational modifications dynamically regulate protein aggregation
      and disaggregation in a very complex, intricate and delicate balance. Areas
      covered: Herein, we overview the more promising techniques and approaches for the
      elucidation of the biological implications of protein aggregation. The particular
      insights provided by different techniques were discriminated and several examples
      of post-translational modifications together with their targets were pooled and
      critically discussed, representing promising future therapeutic targets. Expert
      commentary: In the years to come, differences between physiological and
      pathological protein aggregation will certainly become easier to determine.
      Techniques such as hydrogen/deuterium exchange, circular dichroism spectroscopy
      and novel mass spectrometry-based approaches are being optimized and are expected
      to introduce inhibitors of protein aggregation into the clinic. However, protein
      aggregation is not an isolated phenomenon, but rather influenced by multiple
      cellular components which complete knowledge is still far.

PMID- 27892739
TI  - Efflux as a mechanism of antimicrobial drug resistance in clinical relevant
      microorganisms: the role of efflux inhibitors.
AB  - INTRODUCTION: Microbial resistance against antibiotics is a serious threat to the
      effective treatment of infectious diseases. Several mechanisms exist through
      which microorganisms can develop resistance against antimicrobial drugs, of which
      the overexpression of genes to produce efflux pumps is a major concern. Several
      efflux transporters have been identified in microorganisms, which infer
      resistance against specific antibiotics and even multidrug resistance. Areas
      covered: This paper focuses on microbial resistance against antibiotics by means
      of the mechanism of efflux and gives a critical overview of studies conducted to
      overcome this problem by combining efflux pump inhibitors with antibiotics.
      Information was obtained from a literature search done with MEDLINE, Pubmed,
      Scopus, ScienceDirect, OneSearch and EBSCO host. Expert opinion: Efflux as a
      mechanism of multidrug resistance has presented a platform for improved efficacy
      against resistant microorganisms by co-administration of efflux pump inhibitors
      with antimicrobial agents. Although proof of concept has been shown for this
      approach with in vitro experiments, further research is needed to develop more
      potent inhibitors with low toxicity which is clinically effective.

PMID- 27892740
TI  - How can plasma RNA be used to diagnose prostate cancer?

PMID- 27892741
TI  - Impact of prenatal diagnosis of transposition of the great arteries on postnatal
      outcome.
AB  - OBJECTIVE: To assess the impact of prenatal diagnosis of transposition of the
      great arteries (TGA) on postnatal outcome. METHODS: Hundred and fifty-four
      patients with either simple (n = 101) or complex forms (n = 53) of TGA, diagnosed
      prenatally (G1, n = 88) or postnatally (G2, n = 66), who were admitted and
      underwent surgical correction in our centre between 1998 and 2014, were analysed.
      RESULTS: Prostaglandin E1 (PgE1) infusion and balloon atrial septostomy (BAS)
      were performed in the first 48 h after birth more commonly in G1. The hospital
      mortality rate for the whole group was 7.1%, higher for complex forms (13.2%)
      than for simple TGA (3.9%), (p = 0.034). The overall mortality rate was similar
      in G1 and G2. The mortality for simple TGA was higher when PgE1 infusion and BAS
      were implemented after the first 48 h (p = 0.001). All deaths in G2 occurred in
      patients first receiving PgE1 and BAS beyond 48 h. PgE1 was initiated in the
      first 48 h in most patients (83%) with simple TGA postnatally diagnosed.
      CONCLUSIONS: Adequate measures in the first 48 h after birth are essential to
      reduce the early mortality in TGA, especially in the simple form. This can be
      provided by prenatal diagnosis or by early neonatal clinical suspicion and prompt
      measures.

PMID- 27892742
TI  - A common ancestral DNMT3A-mutated preleukemic clone giving rise to AML and MDS in
      an adolescent girl.

PMID- 27892743
TI  - Muscle strength and knee range of motion after femoral lengthening.
AB  - Background and purpose - Femoral lengthening may result in decrease in knee range
      of motion (ROM) and quadriceps and hamstring muscle weakness. We evaluated
      preoperative and postoperative knee ROM, hamstring muscle strength, and
      quadriceps muscle strength in a diverse group of patients undergoing femoral
      lengthening. We hypothesized that lengthening would not result in a significant
      change in knee ROM or muscle strength. Patients and methods - This prospective
      study of 48 patients (mean age 27 (9-60) years) compared ROM and muscle strength
      before and after femoral lengthening. Patient age, amount of lengthening, percent
      lengthening, level of osteotomy, fixation time, and method of lengthening were
      also evaluated regarding knee ROM and strength. The average length of follow-up
      was 2.9 (2.0-4.7) years. Results - Mean amount of lengthening was 5.2 (2.4-11.0)
      cm. The difference between preoperative and final knee flexion ROM was 2 degrees 
      for the overall group. Congenital shortening cases lost an average of 5% or 6
      degrees  of terminal knee flexion, developmental cases lost an average of 3% or 4
      degrees , and posttraumatic cases regained all motion. The difference in
      quadriceps strength at 45 degrees  preoperatively and after lengthening was not
      statistically or clinically significant (2.7 Nm; p = 0.06). Age, amount of
      lengthening, percent lengthening, osteotomy level, fixation time, and lengthening
      method had no statistically significant influence on knee ROM or quadriceps
      strength at final follow-up. Interpretation - Most variables had no effect on ROM
      or strength, and higher age did not appear to be a limiting factor for femoral
      lengthening. Patients with congenital causes were most affected in terms of knee
      flexion.

PMID- 27892744
TI  - Evaluation of efficacy and safety of different pembrolizumab dose/schedules in
      treatment of non-small-cell lung cancer and melanoma: a systematic review.
AB  - AIM: Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for
      the treatment of advanced melanoma and pretreated non-small-cell lung cancer
      (NSCLC). OBJECTIVE: To assess the efficacy and safety of different dose schedules
      of pembrolizumab in the treatment of patients with advanced NSCLC and melanoma.
      Search method: MEDLINE database has been searched. Reference lists of original
      studies and review articles were checked for other related articles. SELECTION
      CRITERIA: Prospective clinical trials reporting the outcomes of more than one
      dose schedule of pembrolizumab in the treatment of advanced NSCLC and melanoma.
      DATA COLLECTION & ANALYSIS: The review author extracted information on the
      outcomes of the study for this review, and presented the results. MAIN RESULTS:
      Four trials with 3425 patients were included in this systematic review. Pooled
      analysis for the odds ratio of objective response rate comparing 2 versus 10
      mg/kg every 3 weeks in advanced melanoma was 1.03 (95% CI: 0.71-1.49; p = 0.89),
      while for advanced NSCLC, it was 0.97 (95% CI: 0.66-1.43; p = 0.87). Moreover,
      odds ratio for selected side effects between the two doses was as follows: rash:
      0.83 (95 CI: 0.58-1.18; p = 0.29); vitiligo: 1.27 (95% CI: 0.62-2.61; p = 0.52);
      diarrhea: 0.94 (95% CI: 0.63-1.42; p = 0.79); hypothyroidism: 0.97 (95% CI: 0.63
      1.50; p = 0.90); hepatitis/elevated transaminases: 1.86 (95% CI: 0.91-3.79; p =
      0.09); nephritis: 0.88 (95% CI: 0.32-2.44; p = 0.80); pneumonitis: 1.17 (95% CI:
      0.62-2.23; p = 0.63). CONCLUSIONS: Given the equivalence in efficacy and safety
      between lower doses and higher doses of pembrolizumab, 2 mg/kg every 3 weeks
      seems to be an appropriate dose for routine practice in advanced pretreated NSCLC
      and melanoma.

PMID- 27892745
TI  - Gene-expression-based monocyte-specific clustering of acute myeloid leukemias
      reveals novel associations.

PMID- 27892746
TI  - Choroidal Neovascularization Associated with Multiple Evanescent White Dot
      Syndrome Treated with Intravitreal Ranibizumab.
AB  - PURPOSE: To describe the clinical outcomes of intravitreal ranibizumab treatment
      for subfoveal choroidal neovascularization (CNV) associated with multiple
      evanescent white dot syndrome (MEWDS). METHODS: This is a prospective,
      interventional, case series. All recruited patients underwent a baseline
      intravitreal ranibizumab injection and were monitored monthly over a 12-month
      follow-up, following a pro-re-nata regimen. RESULTS: Four patients (four eyes)
      were included in the study. Mean best-corrected visual acuity (BCVA) changed from
      0.60 +/- 0.20 at baseline to 0.07 +/- 0.05 logMAR at 12-month examination.
      Baseline central macular thickness reduced from 330 +/- 32 um to the final value
      of 228 +/- 14 um at the 1-year follow-up. Overall, a mean number of 2.2
      ranibizumab injections were administered at the end of 12 months. CONCLUSIONS:
      Intravitreal ranibizumab treatment represents a valuable therapeutic option for
      the management of CNV associated with MEWDS.

PMID- 27892747
TI  - Blunt tools, burning questions: using cancer registry data to study
      relapsed/refractory lymphoma.

PMID- 27892748
TI  - Are porous tantalum cups superior to conventional reinforcement rings?
AB  - Background and purpose - Porous tantalum cups have been introduced as an
      alternative to various reinforcement rings in revision hip surgery. We
      hypothesized that porous tantalum cups would be superior to Muller acetabular
      roof reinforcement rings (MARRs) in revision hip surgery with re-revision for
      aseptic loosening as the primary outcome measure. Patients and methods - 207 hips
      operated with either a porous tantalum cup (TM cup, n = 111) or a MARR (n = 96)
      at index procedure were identified in our local arthroplasty register. Acetabular
      defects were classified according to Paprosky. There were 96 men and 111 women
      with a median age of 71 (35-95) years, presenting acetabular defect size type I
      in 39 cases, IIA in 22, IIB in 27, IIC in 43, IIIA in 32, and IIIB in 37 cases.
      Analysis of medical records identified all patients with subsequent re-revision
      and reasons for re-revisions. Kaplan-Meier survival functions were used to
      estimate implant survival. Results - With re-revision for aseptic loosening as
      the endpoint, the 6-year unadjusted cumulative survival was 97% (95% CI: 94-100)
      for TM cups and 96% (CI: 92-100) for MARR (p = 0.6). Using re-revision for any
      reason as the endpoint, 6-year survival was 87% (CI: 81-94) for TM cups and 95%
      (CI: 90-99) for MARR (p = 0.06). The main reason for re-revision in the TM group
      was dislocation (n = 10), followed by loosening (n = 3), whereas the main reason
      for re-revision in the MARR group was aseptic loosening (n = 8). Duration of the
      index procedure and perioperative blood loss were lower in the TM group.
      Interpretation - Both TM and MARR lead to good 6-year results in acetabular
      revision surgery. The methods differ in their respective failure mechanisms. We
      conclude that TM cups are a valuable treatment option in acetabular revision
      surgery, but the reasons underlying dislocations after the use of TM cups must be
      analyzed further.

PMID- 27892750
TI  - Risk of hepatitis B reactivation under treatment with tyrosine-kinase inhibitors
      for chronic myeloid leukemia.

PMID- 27892749
TI  - High non-relapse mortality and low relapse incidence in gender-mismatched
      allogeneic hematopoietic stem cell transplantation from a parous female donor
      with a male child.
AB  - To clarify the influence of exposure to a male fetus during a female donor's (FD)
      pregnancy in allogeneic hematopoietic stem cell transplantation (HSCT), we
      retrospectively examined 292 HSCT patients. The 5-year non-relapse mortality
      (NRM) was 33.5% among 31 male recipients who had HSCT from FD with a male child
      (MC), 23.0% among 40 male recipients who had HSCT from FD without MC and 19.6%
      among 221 other recipients. The 5-year relapse incidence (RI) was 22.6%, 42.0%,
      and 43.1% for the respective group. In multivariate analysis, male recipients who
      had HSCT from FD with MC had an increased risk of NRM (hazard ratio [HR] 1.92,
      95% CI 1.08-3.42, p = .03), a reduced risk of RI (HR 0.42, 95% CI 0.18-0.96, p =
      .04), resulting in no significant difference regarding overall survival. Male
      child of FD is suggested to influence NRM and RI in gender-mismatched HSCT.

PMID- 27892751
TI  - Decline in Ocular Toxoplasmosis over 40 Years at a Tertiary Referral Practice in
      the United States.
AB  - PURPOSE: To identify whether there has been a decline in ocular toxoplasmosis at
      a tertiary uveitis practice. METHODS: Retrospective review of new patients at the
      University of Illinois Uveitis Service from 1973 to 2012. RESULTS: There were
      6820 patients with adequate records for inclusion; 323 (4.7%) were diagnosed with
      ocular toxoplasmosis. There was a 78.0% decline in prevalence of ocular
      toxoplasmosis from 2008 to 2012 compared with 1973 to 1977. Compared with the
      aggregate uveitis population, toxoplasmosis patients were more likely to be
      Hispanic (p<0.0001) and less likely to be African American (p<0.0001). Ocular
      toxoplasmosis in Hispanics commonly occurred in foreign-born patients (85.3%).
      CONCLUSIONS: The diagnosis of ocular toxoplasmosis at our clinic declined, with
      Hispanics accounting for an increasing proportion of cases. These trends are
      consistent with the decreasing toxoplasmosis seropositivity in the United States,
      but may also reflect decreased referrals due to improved management of ocular
      toxoplasmosis in primary clinics.

PMID- 27892752
TI  - Concentration dependence of nitroxyl spin probes in liposomal solution: electron
      spin resonance and overhauser-enhanced magnetic resonance studies.
AB  - In this work, the detailed studies of electron spin resonance (ESR) and
      overhauser-enhanced magnetic resonance imaging (OMRI) were carried out for
      permeable nitroxyl spin probe, MC-PROXYL as a function of agent concentration in
      liposomal solution. In order to compare the impermeable nature of nitroxyl
      radical, the study was also carried out only at 2 mM concentration of carboxy
      PROXYL. The ESR parameters were estimated using L-band and 300 MHz ESR
      spectrometers. The line width broadening was measured as a function of agent
      concentration in liposomal solution. The estimated rotational correlation time is
      proportional to the agent concentration, which indicates that less mobile nature
      of nitroxyl spin probe in liposomal solution. The partition parameter and
      permeability values indicate that the diffusion of nitroxyl spin probe
      distribution into the lipid phase is maximum at 2 mM concentration of MC-PROXYL.
      The dynamic nuclear polarization (DNP) parameters such as DNP factor,
      longitudinal relaxivity, saturation parameter, leakage factor and coupling factor
      were estimated for 2 mM MC-PROXYL in 400 mM liposomal dispersion. The spin
      lattice relaxation time was shortened in liposomal solution, which leads to the
      high relaxivity. Reduction in coupling factor is due to less interaction between
      the electron and nuclear spins, which causes the reduction in enhancement. The
      leakage factor increases with increasing agent concentration. The increase in DNP
      enhancement was significant up to 2 mM in liposomal solution. These results paves
      the way for choosing optimum agent concentration and OMRI scan parameters used in
      intra and extra membrane water by loading the liposome vesicles with a lipid
      permeable nitroxyl spin probes in OMRI experiments.

PMID- 27892753
TI  - Severe hip displacement reduces health-related quality of life in children with
      cerebral palsy.
AB  - Background and purpose - Hip displacement is common in children with severe
      cerebral palsy (CP) and can cause problems such as pain, contractures, and
      nursing difficulties. Caregiver priorities and child health index of life with
      disabilities (CPCHILD) is a recently developed measure of health-related quality
      of life (HRQL) in children with severe CP. The associations between CPCHILD
      scores and hip displacement have not been investigated. We explored the effect of
      hip displacement on HRQL. Patients and methods - 67 children were recruited from
      the population-based Norwegian CP register. Mean age was 9 (7-12) years. There
      were 40 boys. Gross motor function classification system (GMFCS) distribution was
      12 level III, 17 level IV, and 38 level V. Hip displacement was assessed by
      radiographic migration percentage (MP). The criterion for hip displacement was MP
      of the worst hip of >=40%. Primary caregivers responded to 5 of the 6 domains of
      the CPCHILD questionnaire. Results - Hip displacement was found in 18 children
      and it was significantly associated with lower scores on the CPCHILD domains 3
      (Comfort and Emotions) and 5 (Health), but not with domains 1 (Activities of
      Daily Living/Personal Care), 2 (Positioning, Transfer, and Mobility), and 6
      (Overall Quality of Life). GMFCS level V was a significant predictor of low
      scores in all the domains. Interpretation - For the assessment of HRQL in
      children with severe CP and hip problems, we propose a modified and simplified
      version of the CPCHILD consisting of 14 of 37 questions. This would reduce the
      responders' burden and probably increase the response rate in clinical studies
      without losing important information.

PMID- 27892754
TI  - Amputation following internal fixation of an ankle fracture via the
      posterolateral approach - a case report.

PMID- 27892755
TI  - Association of single-nucleotide polymorphisms in non-coding regions of the TLR4
      gene with primary open angle glaucoma in a Mexican population.
AB  - BACKGROUND: Toll-like receptor 4 (TLR4) non-coding polymorphisms are associated
      to primary open angle glaucoma (POAG), normal tension glaucoma, and
      pseudoexfoliation glaucoma. This study was performed to determine whether non
      coding single nucleotide polymorphisms (SNPs) in the TLR4 gene contribute to POAG
      in a Mexican population. MATERIAL AND METHODS: A total of 187 unrelated Mexican
      patients with POAG and 109 control subjects were included. Allelic, genotypic,
      and haplotypic diversity was assessed for the non-coding polymorphisms
      rs11536889, rs1927911, rs12377632, and rs2149356 of the TLR4 gene. Genotyping of
      target SNPs was performed by 5' exonuclease allelic discrimination assays.
      RESULTS: Strong linkage disequilibrium was observed among the SNPs (D' > 0.818),
      which were located in one haplotype block. The rs11536889 polymorphism was not
      associated to POAG in any case. The frequency of the minor allele of rs2149356
      was significantly higher in the glaucoma group, conferring an increased risk of
      POAG (p = 0.0018, OR = 1.803, 95% CI 1.2556-2.5890) whereas minor allele of
      rs12377632 was significantly lower, attributing a protective effect (p = 0.0001,
      OR = 0.6662, 95% CI 0.4753-0.9339). Subjects with genotypes carrying the minor
      allele of rs1927911 and rs2149356 shown an increased risk for POAG (p = 0.03, OR
      = 1.78, 95% CI 1.10-2.87, and p < 0.0004, OR =2.62, 95%CI 1.61-4.27
      respectively). Finally, we found significant risk haplotypes. The GTT haplotype
      (constituted by rs1927911, rs12377632, and rs2149356) reached the higher OR (p =
      0.0026, OR = 4.70, 95% CI 1.73-12.77). CONCLUSIONS: We have identified intronic
      TLR4 SNPs as genetic susceptibility alleles for POAG in a Mexican population. Our
      findings support the association of the TLR4 gene with POAG.

PMID- 27892756
TI  - Use of high noninvasive respiratory support pressures in preterm neonates: a
      single-center experience.
AB  - PURPOSE: To describe the incidence, indications and clinical outcomes following
      high pressures on noninvasive respiratory support (NRS) in preterm neonates.
      STUDY DESIGN: Retrospective cohort study of all neonates with BW <1.500 g
      admitted from July 2012 to June 2014 and placed on high noninvasive respiratory
      support (NRS), defined as mean airway pressure >=10 cm H2O for at least 12
      continuous hours using nasal continuous positive airway pressure (NCPAP) and/or
      nasal high-frequency ventilation (NIHFV). Clinical and physiological outcomes
      following high NRS were ascertained. Median (IQR) and percentages were used to
      describe continuous and categorical data, respectively. RESULTS: There were 131
      instances of high NRS use in 70 of 315 eligible infants. Most common indication
      was post-extubation, observed in 37% (49/131) of high NRS instances. Intubation
      was avoided in 71% (93/131) of instances in the first 7 days following high NRS
      initiation. There were no physiological perturbations in heart rate, blood
      pressure or oxygen requirement. Furthermore, there were no instances of lung
      hyperinflation, pneumothoraces or spontaneous intestinal perforation following
      high NRS. CONCLUSION: The use of high NRS pressure was followed by avoidance of
      intubation in the majority of cases without adverse effects. Further research on
      high NRS use including its indications, clinical outcomes and safety profile is
      warranted.

PMID- 27892758
TI  - Gamma radiation tolerance in different life stages of the fruit fly Drosophila
      melanogaster.
AB  - PURPOSE: Insects are known to have higher levels of radiation tolerance than
      mammals. The fruit fly Drosophila provides opportunities for genetic analysis of
      radiation tolerance in insects. A knowledge of stage-specific sensitivity is
      required to understand the mechanisms and test the existing hypothesis of insect
      radiation tolerance. MATERIALS AND METHODS: Drosophila melanogaster were
      irradiated using gamma rays at different life stages. Irradiation doses were
      chosen to start from 100-2200 Gy with increments of 100 Gy, with a dose rate of
      12.5 and 25 Gy/min. The threshold of mortality, LD50 and LD100 1 h post
      irradiation was recorded for larvae and adults and 24 h post-irradiation for eggs
      and after 2-3 days for early and late pupae. Total antioxidant capacity for all
      the life stages was measured using the phosphomolybdenum method. RESULTS: Twenty
      four hours post-irradiation, 100% mortality was recorded for eggs at 1000 Gy. One
      hour post irradiation 100% mortality was recorded at 1300 Gy for first instar
      larvae, 1700 Gy for second instar larvae, 1900 Gy for feeding third instar larvae
      and 2200 Gy for non-feeding third instar larvae. Post-irradiation complete
      failure of emergence (100% mortality) was observed at 130 Gy for early pupae and
      1500 Gy for late pupae; 100% mortality was observed at 1500 Gy for adults. The
      values of LD50 were recorded as 452 Gy for eggs, 1049 Gy for first instar larvae,
      1350 Gy for second instar larvae, 1265 Gy for feeding third instar larvae, 1590
      Gy for non-feeding third instar larvae, 50 Gy for early pupae, 969 Gy for late
      pupae, 1228 Gy for adult males and 1250 Gy for adult females. CONCLUSIONS: Early
      pupae were found to be prone to radiation, whereas the non-feeding third instar
      larvae were most resistant among all stages. The chromosome number being constant
      and total antioxidant capacity being nearly constant in all stages, we suggest
      that high rate of cell division during early pupae makes this stage sensitive to
      radiation.

PMID- 27892757
TI  - Basic principles and current status of transcorneal and transscleral
      iontophoresis.
AB  - INTRODUCTION: Iontophoresis is an active non-invasive drug delivery technique
      that can increase the transport of charged and neutral molecules into and across
      biological membranes. Most research to-date has focused on (per)cutaneous
      iontophoretic drug delivery. However, recent studies illustrate its potential for
      drug delivery to the eye: corneal iontophoresis may enable targeted topical
      therapy of intracorneal diseases, whereas transscleral iontophoresis may enable
      non-invasive intraocular drug delivery. Areas covered: We describe iontophoretic
      principles in the context of ocular delivery before providing a summary of recent
      preclinical studies involving transcorneal and transscleral iontophoresis in
      vitro and in vivo. Subsequently, an overview of clinical applications with
      special focus on the transcorneal iontophoresis of riboflavin for corneal cross
      linking and transscleral iontophoresis of corticosteroids for the treatment of
      posterior segment diseases is provided. Expert opinion: The feasibility of using
      iontophoresis for ocular drug delivery has been demonstrated. Drug formulation
      development and the ability to design iontophoretic applicators will now
      determine its success in the clinic. The specificities of the ocular globe must
      be taken into account; in particular, its unique morphology, and the smaller
      surface area available for drug diffusion and the fact that it is more
      susceptible to irritation and less robust than the skin.

PMID- 27892759
TI  - The use of ketamine in ECT anaesthesia: A systematic review and critical
      commentary on efficacy, cognitive, safety and seizure outcomes.
AB  - OBJECTIVES: This review will discuss ECT efficacy and cognitive outcomes when
      using ketamine as an ECT anaesthetic compared to other anaesthetics, taking into
      account important moderator variables that have often not been considered to
      date. It will also include information on safety and other ECT outcomes (seizure
      threshold and quality). METHODS: A systematic search through MEDLINE, PubMed,
      PsychINFO, Cochrane Databases and reference lists from retrieved articles was
      performed. Search terms were: "ketamine" and "Electroconvulsive Therapy", from
      1995 to September 2016. Meta-analyses, randomised controlled trials, open-label
      and retrospective studies published in English of depressed samples receiving ECT
      with ketamine anaesthesia were included (n = 24). RESULTS: Studies were
      heterogeneous in the clinical populations included and ECT treatment and
      anaesthetic methods. Frequently, studies did not report on ECT factors (i.e.,
      pulse-width, treatment schedule). Findings regarding efficacy were mixed.
      Tolerance from repeated use may explain why several studies found that ketamine
      enhanced efficacy early in the ECT course but not at the end. The majority of
      studies did not comprehensively examine cognition and adverse effects were not
      systematically studied. Only a minority of the studies reported on seizure
      threshold and expression. CONCLUSIONS: The routine use of ketamine anaesthesia
      for ECT in clinical settings cannot yet be recommended based on published data.
      Larger randomised controlled trials, taking into account moderator variables,
      specifically reporting on ECT parameters and systematically assessing outcomes
      are encouraged.

PMID- 27892760
TI  - Microbubble-mediated ultrasound drug-delivery and therapeutic monitoring.
AB  - INTRODUCTION: Recent developments in ultrasound imaging and ultrasound contrast
      agents (UCAs) improved diagnostic confidence in echography and set into motion
      their combined use as a tool for drug delivery and therapeutic monitoring. Non
      invasive, precise and targeted delivery of drug molecules to pathological tissues
      by employing different mechanisms of drug release is becoming feasible. Areas
      covered: We sought to describe: the nature and features of UCAs; outline current
      contrast-specific imaging modes; before describing a variety of strategies for
      using ultrasound and microbubbles as a drug delivery system. Our expert opinion
      focusses on results and prospects of using ultrasound and microbubbles as a dual
      modality for drug delivery and therapeutic monitoring. Expert opinion: Today,
      ultrasound and microbubbles present a realistic prospect as drug delivery tools
      that have been demonstrated in a variety of animal models and clinical
      indications. Besides delivering drugs, ultrasound and microbubbles have
      demonstrated added value through therapeutic monitoring and assessment.
      Successful evaluation of the sonoporation mechanism(s), ultrasound parameters,
      drug type and dose will need to be addressed before translating this technology
      for clinic use. Ultimately, the development of a strategy for monitoring targeted
      delivery and its implementation in clinical practice would advance therapeutic
      treatment to a new qualitative level.

PMID- 27892761
TI  - Autonomic markers associated with generalized social phobia symptoms: heart rate
      variability and salivary alpha-amylase.
AB  - The study of autonomic nervous system changes associated with generalized social
      phobia (GSP) disorder has increased in recent years, showing contradictory
      results. The present study aimed to evaluate how young people with GSP reacted
      before, during, and after exposure to the Trier Stress Social Test (TSST),
      focusing on their autonomic changes (heart rate variability (HRV) and salivary
      alpha-amylase (sAA)) compared to a control group (non-GSP). Some psychological
      variables were also considered. Sex was specifically studied as a possible
      modulator of autonomic fluctuations and psychological state. Eighty young people
      were randomly distributed into two counterbalanced situations: stress condition
      (N = 18 and 21 for GSP and non-GSP, respectively) and control condition (N = 21
      and 20 for GSP and non-GSP, respectively), where cardiovascular variables were
      continuously recorded. Psychological questionnaires about mood and perceived
      stress were filled out, and five saliva samples were collected to analyze sAA.
      GSP participants showed higher values on low- and high-frequency ratios (HR
      domains), compared to non-GSP people, during exposure to the TSST, but no
      differences were observed after the stressor. Furthermore, the two groups did not
      differ in sAA. Importantly, positive affect in GSP participants was modulated by
      sex. The present study suggests that the balance between high- and low-frequency
      domains of HRV is a key cardiovascular marker reflecting the stress response of
      GSP people, as well the importance of sex in positive affect when facing a
      stressful situation.

PMID- 27892762
TI  - Functional inter-cortical connectivity among motor-related cortices during motor
      imagery: A magnetoencephalographic study.
AB  - Neural connectivity was measured during motor imagery (MI) and motor execution
      (ME) using magnetoencephalography in nine healthy subjects, MI, and at rest.
      Lower coherence values during ME and MI between sensorimotor areas than at rest,
      and lower values during MI between the left supplementary motor area and inferior
      frontal gyrus than ME suggested the sensorimotor network of MI functioned with
      similar connectivity to ME and that the inhibitory activity functioned
      continuously during MI, respectively.

PMID- 27892765
TI  - Comparison of predictability for human pharmacokinetics parameters among monkeys,
      rats, and chimeric mice with humanised liver.
AB  - 1. The aim of the present study was to evaluate the usefulness of chimeric mice
      with humanised liver (PXB mice) for the prediction of clearance (CLt) and volume
      of distribution at steady state (Vdss), in comparison with monkeys, which have
      been reported as a reliable model for human pharmacokinetics (PK) prediction, and
      with rats, as a conventional PK model. 2. CLt and Vdss values in PXB mice,
      monkeys and rats were determined following intravenous administration of 30
      compounds known to be mainly eliminated in humans via the hepatic metabolism by
      various drug-metabolising enzymes. Using single-species allometric scaling, human
      CLt and Vdss values were predicted from the three animal models. 3. Predicted CLt
      values from PXB mice exhibited the highest predictability: 25 for PXB mice, 21
      for monkeys and 14 for rats were predicted within a three-fold range of actual
      values among 30 compounds. For predicted human Vdss values, the number of
      compounds falling within a three-fold range was 23 for PXB mice, 24 for monkeys,
      and 16 for rats among 29 compounds. PXB mice indicated a higher predictability
      for CLt and Vdss values than the other animal models. 4. These results
      demonstrate the utility of PXB mice in predicting human PK parameters.

PMID- 27892766
TI  - A Backward Glance for Tempus.

PMID- 27892767
TI  - Epigenetic modifications in multiple myeloma: recent advances on the role of DNA
      and histone methylation.
AB  - INTRODUCTION: Multiple Myeloma (MM) is a clonal late B-cell disorder accounting
      for about 13% of hematological cancers and 1% of all neoplastic diseases. Recent
      studies on the molecular pathogenesis and biology of MM have highlighted a
      complex epigenomic landscape contributing to MM onset, prognosis and high
      individual variability. Areas covered: We describe here the current knowledge on
      epigenetic events characterizing MM initiation and progression, focusing on the
      role of DNA and histone methylation and on the most promising epi-therapeutic
      approaches targeting the methylation pathway. Expert opinion: Data published so
      far indicate that alterations of the epigenetic framework, which include aberrant
      global or gene/non-coding RNA specific methylation profiles, feature prominently
      in the pathobiology of MM. Indeed, the aberrant expression of components of the
      epigenetic machinery as well as the reversibility of the epigenetic marks make
      this pathway druggable, providing the basis for the design of epigenetic
      therapies against this still fatal malignancy.

PMID- 27892764
TI  - STAT3-mediated SMAD3 activation underlies Oncostatin M-induced Senescence.
AB  - Cytokines in the developing tumor microenvironment (TME) can drive transformation
      and subsequent progression toward metastasis. Elevated levels of the Interleukin
      6 (IL-6) family cytokine Oncostatin M (OSM) in the breast TME correlate with
      aggressive, metastatic cancers, increased tumor recurrence, and poor patient
      prognosis. Paradoxically, OSM engages a tumor-suppressive, Signal Transducer and
      Activator of Transcription 3 (STAT3)-dependent senescence response in normal and
      non-transformed human mammary epithelial cells (HMEC). Here, we identify a novel
      link between OSM-activated STAT3 signaling and the Transforming Growth Factor
      beta (TGF-beta) signaling pathway that engages senescence in HMEC. Inhibition of
      functional TGF-beta/SMAD signaling by expressing a dominant-negative TGF-beta
      receptor, treating with a TGF-beta receptor inhibitor, or suppressing SMAD3
      expression using a SMAD3-shRNA prevented OSM-induced senescence. OSM promoted a
      protein complex involving activated-STAT3 and SMAD3, induced the nuclear
      localization of SMAD3, and enhanced SMAD3-mediated transcription responsible for
      senescence. In contrast, expression of MYC (c-MYC) from a constitutive promoter
      abrogated senescence and strikingly, cooperated with OSM to promote a transformed
      phenotype, epithelial-mesenchymal transition (EMT), and invasiveness. Our
      findings suggest that a novel STAT3/SMAD3-signaling axis is required for OSM
      mediated senescence that is coopted during the transformation process to confer
      aggressive cancer cell properties. Understanding how developing cancer cells
      bypass OSM/STAT3/SMAD3-mediated senescence may help identify novel targets for
      future "pro-senescence" therapies aiming to reengage this hidden tumor
      suppressive response.

PMID- 27892768
TI  - TFEB and TFE3: The art of multi-tasking under stress conditions.
AB  - Cellular adaptation response to a myriad of stressors is key for survival. The
      lysosomal/autophagy pathway is inextricably connected to the stress response
      regulation. Two transcription factors, TFEB and TFE3, have recently emerged as
      master regulators of this degradative pathway. Their function modulating
      different cellular pathways will be discussed.

PMID- 27892770
TI  - Myocardial infarction with non obstructive coronary arteries (MINOCA): a whole
      new ball game.
AB  - INTRODUCTION: MINOCA is a clinical syndrome that encompasses a subgroup of
      heterogeneous patients who present with myocardial infarction yet do not have any
      significant coronary artery obstruction on angiogram. As many as one in ten
      patients with acute myocardial infarction (AMI) will not have an occluded
      coronary artery, and the reported prevalence keeps rising, in part due to better
      recognition of this syndrome. Current guidelines offer several diagnostic
      algorithms but MINOCA remains largely under-recognised and little is known about
      whether patients might benefit from a more specific treatment modality. Areas
      covered: We review pathogenesis, diagnosis, prognosis, and management of MINOCA.
      Expert commentary: Due to the significant heterogeneity of MINOCA patients, a
      more efficient management strategy may solely rely on an individualized approach
      in order to improve outcomes.

PMID- 27892769
TI  - CircRNAs in the brain.
AB  - Circular RNAs (circRNAs) are highly abundant and evolutionarily conserved non
      coding RNAs produced by circularization of specific exons. Since their re
      discovery as potential regulators of gene expression, thousands of circRNAs were
      detected in different tissues and cell types across most organisms. Accumulating
      data suggest key roles for them in the central nervous system. Neuronal-expressed
      RNAs are diverted to yield highly enriched CircRNAs in human, mouse, pig and
      flies, with many of them enriched in neuronal tissues. CircRNA levels are
      dynamically modulated in neurons, both during differentiation and following
      bursts of electrical activity, and accumulate with age, and many of them are
      enriched in synapses. Together, available data suggest that circRNAs have
      important roles in synaptic plasticity and neuronal function. This review covers
      current advances in the field and lays out hypotheses regarding functions of
      circRNAs in the brain as well as their putative involvement in initiation and
      progression of neurodegenerative processes.

PMID- 27892773
TI  - Real-world data on nivolumab treatment of non-small cell lung cancer.
AB  - BACKGROUND: Checkpoint inhibitors have proven effectiveness in clinical trials
      for non-small cell lung cancer (NSCLC) patients, but if this is congruent with
      routine patient care is discussed. We present real-world experience with the PD1
      inhibitor nivolumab in NSCLC. PATIENTS AND METHODS: Patients with NSCLC were
      considered eligible for nivolumab treatment after one or more lines of
      chemotherapy, and when in reasonable performance status (PS) [Eastern Cooperative
      Oncology Group (ECOG) < 3]. Treatment was given according to guidelines in the
      two phase III studies, CA209017 and CA209057. Response evaluation was done
      according to Recist 1.1, and treatment given until unequivocal progression or
      intolerable toxicity. RESULTS: Fifty-eight patients (30 females) commenced
      therapy in the period June-August 2015. Median age was 64.6 years (range 32.3
      88.2). Twenty-four patients had squamous cell carcinoma and 32 adenocarcinoma, 38
      had received two or more prior lines of therapy. Fourteen cases (24%) were in
      ECOG PS 2. After a medium observation time of 14.3 months, 13 (22%) are still in
      treatment. Median time to treatment failure (TTF) was 4.0 months, 34% were off
      treatment during the first two months. Median overall survival (OS) is 11.7
      months. There was no difference in TTF or OS among patients with squamous versus
      non-squamous histology or between 1 versus >1 prior line of therapy. Four
      patients (7%) were off treatment due to toxicity, none were grade 4 or 5.
      CONCLUSION: Nivolumab treatment outside clinical trials seems to perform as
      expected.

PMID- 27892772
TI  - Administration of lidocaine to prevent cognitive deficit in patients undergoing
      coronary artery bypass grafting and valve plasty: a systematic review and meta
      analysis.
AB  - INTRODUCTION: The administration of lidocaine to maintain cognitive function
      following coronary artery bypass grafting (CABG) and valve plasty is a
      controversial concept in terms of its effectiveness. We performed a systematic
      review to determine the effectiveness of treatment with lidocaine in preventing
      the occurrence of cognitive deficit after cardiac surgery. Area covered: To
      review the current literature on the subject, we searched the PubMed database and
      the Cochrane Library database (up to May 2015) and compiled a list of retrieved
      articles. Our final review includes only randomized controlled trials (RCTs) that
      compared lidocaine to a control (placebo) following CABG and valve plasty.
      Statistical analysis of the odds ratio (OR) and corresponding 95% confidence
      interval (CI) were used to determine the overall effectiveness of lidocaine for
      the prevention of cognitive deficit with both procedures. The Mantel-Haenszel
      method was used to pool data of the outcomes of cognitive deficit occurrence into
      fixed-effect model meta-analyses. Five RCTs were included in this study, with a
      total of 688 patients. Perioperative administration of lidocaine in patients
      undergoing cardiac surgery reduced occurrence of cognitive deficit (OR 0.583 [95%
      CI 0.438-0.777]; Z = -3.680; P = 0.00; I2 = 52%). No significant difference in
      the early occurrence of cognitive deficit was revealed in patients after cardiac
      surgery (OR 0.909 [95% CI 0.600-1.376]; Z = -0.451; P = 0.652; I2 = 11%). Expert
      commentary: Cognitive deficit associated with cardiac surgery is a common
      postoperative event. Lidocaine is contributed to a significantly reduced
      occurrence of cognitive deficit. Cognitive deficit management is recommended.

PMID- 27892771
TI  - A tRNA-derived fragment competes with mRNA for ribosome binding and regulates
      translation during stress.
AB  - Posttranscriptional processing of RNA molecules is a common strategy to enlarge
      the structural and functional repertoire of RNomes observed in all 3 domains of
      life. Fragmentation of RNA molecules of basically all functional classes has been
      reported to yield smaller non-protein coding RNAs (ncRNAs) that typically possess
      different roles compared with their parental transcripts. Here we show that a
      valine tRNA-derived fragment (Val-tRF) that is produced under certain stress
      conditions in the halophilic archaeon Haloferax volcanii is capable of binding to
      the small ribosomal subunit. As a consequence of Val-tRF binding mRNA is
      displaced from the initiation complex which results in global translation
      attenuation in vivo and in vitro. The fact that the archaeal Val-tRF also
      inhibits eukaryal as well as bacterial protein biosynthesis implies a
      functionally conserved mode of action. While tRFs and tRNA halves have been amply
      identified in recent RNA-seq project, Val-tRF described herein represents one of
      the first functionally characterized tRNA processing products to date.

PMID- 27892774
TI  - Further insight into prognostic factors in endometrial cancer: the new serum
      biomarker HE4.
AB  - INTRODUCTION: Endometrial cancer (EC) is one of the most common gynecological
      cancer worldwide. To date, no good markers are routinely used in clinical
      practice for prognosis and monitoring. Areas covered: During the last years, an
      increasing interest in literature has been growing on HE4 (Human epididimis 4).
      Therefore, we aimed to gather all the evidence reported in literature analysing
      the potential prognostic value of HE4, compared to the well know tumor's features
      (histological type and grade, stage of disease, depth of myometrial invasion,
      lymphovascular space involvement and cervical involvement). Expert commentary:
      The analysis of data suggests that HE4 seems to have a good performance in
      prognosis and monitoring of the disease, helping to schedule the appropriste
      timing of imaging and surgery in a more individualized fashion. However, these
      findings surely require a validation in a larger cohorts of patients. Probably,
      in the next five years, prospective randomized trials will be performed to
      confirm the prognostic role of HE4 in EC and to find a tailored EC management
      strategy.

PMID- 27892775
TI  - The Emotion Word Fluency Test (EWFT): Initial psychometric, validation, and
      physiological evidence in young adults.
AB  - INTRODUCTION: The clinical assessment of affective functioning has been slow to
      incorporate findings from affective neuroscience. Of particular interest in the
      current study is the assessment of affective word production. METHOD: In a series
      of four studies, we examined test-retest and interrater reliability for the
      Emotion Word Fluency Test (EWFT), basic construct validity with existing verbal
      fluency measures, physiological responses across verbal fluency tasks, and a
      novel scoring method to examine qualitative aspects of participant response sets.
      RESULTS: Results demonstrated interrater and test-retest reliability values that
      were comparable to those of other commonly used verbal fluency tests. Construct
      validity was demonstrated by relations between the EWFT and other verbal fluency
      tests as well as through physiological evidence that performance on the EWFT is
      related to greater sympathetic activity than traditional verbal fluency tasks.
      Lastly, some of the novel scoring metrics related to two self-report measures of
      emotional functioning. CONCLUSIONS: Taken together, our findings provide initial
      support for the use of the EWFT as a measure of emotion word generation ability
      in young adults. This measure may prove to be useful in the assessment of
      affective language production in patient populations.

PMID- 27892776
TI  - Cognitive and affective predictors of boredom proneness.
AB  - Boredom proneness has been linked to various forms of cognitive and affective
      dysregulation including poor self-control and mind-wandering (MW), as well as
      depression and aggression. As such, understanding boredom and the associated
      cognitive and affective components of the experience, represents an important
      first step in combatting the consequences of boredom for psychological well
      being. We surveyed 1928 undergraduate students on measures of boredom proneness,
      self-control, MW, depression and aggression to investigate how these constructs
      were related. Hierarchical regression analysis indicated that self-control
      operated as a strong negative predictor of boredom proneness. Finally, when
      controlling for age and self-control, we observed large decreases in the
      magnitudes of the relationships between boredom proneness and our other measures
      of interest. Together, these results imply a strong relationship between boredom
      proneness and cognitive and affective dysregulation, and show that individual
      levels of self-control can account for the lion's share of variance in the
      relationships between boredom, cognition, and affect.

PMID- 27892777
TI  - Uveitis and Papillitis in the Setting of Dabrafenib and Trametinib Therapy for
      Metastatic Melanoma: A Case Report.
AB  - PURPOSE: To report the diagnosis of acute VKH-like syndrome as a complication
      from dabrafenib (a serine/threonine inhibitor of BRAF V600) and trametinib (a MEK
      inhibitor). In combination, these targeted agents have been shown to prolong
      overall survival and progression free survival in BRAF mutant metastatic
      melanoma. METHODS: Retrospective medical chart review including radiologic and
      ophthalmologic investigations. RESULTS: A patient with metastatic melanoma being
      treated with dabrafenib and trametinib for 2 months presented with 1 week of
      visual blurring. He had developed bilateral optic disc swelling and uveitis that
      responded to pulsed steroid therapy. CONCLUSIONS: VKH-like syndrome is a rare but
      serious complication of targeted therapy that should be considered when
      evaluating a patient with visual disturbances on dabrafenib and trametinib
      therapy.

PMID- 27892779
TI  - Causes of stillbirth in a socioeconomically disadvantaged urban Australian
      population - a comprehensive analysis.
AB  - INTRODUCTION: The aim of this paper was to provide an in-depth analysis of all
      stillbirth causation over a period of 10 years in a busy maternity unit located
      in a socioeconomically disadvantaged urban area, with an emphasis on overlapping
      pathology. MATERIALS AND METHODS: A retrospective analysis of all structurally
      normal stillbirths in singleton pregnancies born during 2002-2012. The PSANZ
      stillbirth classification was used; per stillbirth subgroup main risk factors
      were evaluated. RESULTS: Out of 130 cases, 43% showed overlapping pathologies. In
      the remaining 74 (56%) cases, the following single pathologies were found: IUGR
      20 (15%), infection 12 (9%), abruption 8 (6%), placental thrombotic pathology 8
      (6%), miscellaneous 6 stillbirths (5%), and 20 cases (15%) unexplained. Smoking
      was a risk factor for stillbirth associated with abruption (OR 3.639), infection
      (OR 2.271), and thrombotic pathology (OR 2.168). Drug use had an association with
      (placental) infection (OR 3.598). Obesity showed a significant association with
      IUGR (OR 3.782) and abruption (OR 9.040). Thrombophilia risk analysis for the
      overall group of stillbirths showed significant results for Protein S (OR 8.889)
      and homocysteine >90th centile (OR 2.087). CONCLUSIONS: Overlapping pathology was
      identified in 43% of stillbirths. Infection, IUGR, and abruption were the most
      important single cause of stillbirth.

PMID- 27892778
TI  - First report of palmar fibromatosis and camptodactyly in the 2nd century AD?

PMID- 27892780
TI  - Associations between prolonged sedentary time and breaks in sedentary time with
      cardiometabolic risk in 10-14-year-old children: The HAPPY study.
AB  - This study examines the association between prolonged sedentary time and breaks
      in sedentary time with cardiometabolic risk in 10-14-year-old children. This
      cross-sectional design study analysed accelerometry-determined sedentary
      behaviour and physical activity collected over 7 days from 111 (66 girls) UK
      schoolchildren. Objective outcome measures included waist circumference, fasting
      lipids, fasting glucose, blood pressure, and cardiorespiratory fitness. Logistic
      regression was used for the main data analysis. After adjustment for confounders,
      the odds of having hypertriglyceridaemia (P = 0.03) and an increased clustered
      cardiometabolic risk score (P = 0.05) were significantly higher in children who
      engaged in more prolonged sedentary bouts per day. The number of breaks in
      sedentary time per day was not associated with any cardiometabolic risk factor,
      but longer mean duration of daily breaks in sedentary time were associated with a
      lower odds of having abdominal adiposity (P = 0.04) and elevated diastolic blood
      pressure (P = 0.01). These associations may be mediated by engagement in light
      activity. This study provides evidence that avoiding periods of prolonged
      uninterrupted sedentary time may be important for reducing cardiometabolic
      disease risk in children.

PMID- 27892781
TI  - Analysis and Prediction of Claustrophobia during MR Imaging with the
      Claustrophobia Questionnaire: An Observational Prospective 18-month Single-Center
      Study of 6500 Patients.
AB  - Purpose To analyze claustrophobia during magnetic resonance (MR) imaging and to
      explore the potential of the 26-item claustrophobia questionnaire (CLQ) (range, 0
      4) as a screening tool in patients scheduled for MR imaging. Materials and
      Methods The study received institutional review board approval, and patients in
      the CLQ cohort provided informed consent. A total of 6520 consecutive patients
      were included. Overall, 4288 patients completed the CLQ before MR imaging (CLQ
      cohort), and 2232 patients underwent MR imaging without having completed the CLQ
      (non-CLQ cohort). Claustrophobic events were recorded by the staff. Results The
      CLQ mean score in patients with claustrophobic events (1.48 +/- 0.93) was
      significantly higher (P < .01) than in the group without claustrophobic events
      (0.60 +/- 0.5). The CLQ cutoff value was 0.16 for men and 0.56 for women. Because
      of the low prevalence, negative predictive values of CLQ cutoff values (men, 0.99
      [573 of 582]; women, 0.97 [745 of 766]) were higher than positive predictive
      values (men, 0.01 [88 of 582]; women, 0.16 [192 of 1186]). The overall
      claustrophobic event rate was 9.8% (640 of 6520; 95% confidence interval [CI]:
      9.1, 10.6). The CLQ did not induce claustrophobic events because the event rate
      in the CLQ cohort was significantly lower than that in the non-CLQ cohort, as
      shown by the adjusted odds ratio of 0.81 (95% CI: 0.68, 0.96). Conclusion The CLQ
      is a suitable screening tool for the absence of a subsequent claustrophobic
      event. Furthermore, while it is possible to identify patients with a considerable
      risk of claustrophobia, prediction in individual patients is not possible. (c)
      RSNA, 2016 Online supplemental material is available for this article.

PMID- 27892782
TI  - C1858T Polymorphism of Protein Tyrosine Phosphatase Non-receptor Type 22
      (PTPN22): an eligible target for prevention of type 1 diabetes?
AB  - INTRODUCTION: In type 1 diabetes (T1D), several genetic factors are associated to
      beta-cell autoimmunity onset and clinical progression. HLA-genes play a major
      role in susceptibility and initiation of beta-cell autoimmunity, whereas non-HLA
      genes may influence the destruction rate. Areas covered: Our review focuses on
      the possible role of the PTPN22 C1858 T variant as a prognostic factor, given its
      influence on disease variability. Moreover, we present the potential role of
      C1858 T as a target for tertiary prevention trials and new therapeutic
      strategies, such as the LYP inhibitors. We used PubMed for literature research;
      key words were 'PTPN22', 'C1858 T polymorphism', 'lymphoid-specific tyrosine
      phosphatase' and 'type 1 diabetes'. We selected publications between 2000 and
      2016. Expert commentary: Current data suggest that PTPN22 can be a promising
      target for therapeutic interventions and identification of at-risk subjects in
      autoimmune diseases such as T1D.

PMID- 27892783
TI  - Hen egg white lysozyme is a hidden allergen in Italian commercial ciders.
AB  - Hen egg white lysozyme (HEWL) is an enzyme used in alcoholic fermentation for its
      ability to control the growth of Gram-positive and spoilage bacteria, without
      inhibiting yeast growth, and it allows a reduction in the use of sulphur dioxide.
      Nevertheless, considering the potential allergenicity of this protein, the
      presence of HEWL should be declared on the label of the final product. In this
      work, we analysed 18 commercial Italian ciders by LC-MS/MS and found traces of
      HEWL in 12 samples without label declaration. We used Western blot and enzyme
      linked immunosorbent assay (ELISA) to verify the immunological activity of HEWL,
      and to quantify its content in the ciders. Two out of 18 samples were found to be
      positive both by immunoblot and ELISA. The results indicate the requirement of a
      more stringent control of commercial ciders and the need of label declaration for
      ciders treated with such compounds.

PMID- 27892787
TI  - Corrigendum.

PMID- 27892784
TI  - Management and outcome challenges in newborns with gastroschisis: A 6-year
      retrospective French study.
AB  - OBJECTIVE: To identify the gestational age (GA) at which risk of mortality and
      severe outcome was minimized comparing preterm delivery and expectant management.
      METHODS: Retrospective study performed between 2009 and 2014 of newborns with
      gastroschisis in three large French level III neonatal intensive care units. Each
      department followed two distinct strategies: elective delivery at 35 weeks' GA
      and a delayed approach. RESULTS: We included 69 gastroschisis cases. The lengths
      of stay lasting more than 60 days were significantly greater in the planned
      delivery group than in the expectant approach group (18/30 (60%) vs. 8/39
      (20.5%), p = 0.001). Gastroschisis cases receiving antenatal corticoids during
      the last two weeks of gestation required significantly less surgeries during
      their initial stay (p = 0.003) as well as shorter parenteral feedings (p =
      0.002). A multivariate logistic regression showed that a GA of less than 36
      weeks' GA was is a pejorative factor for a stay above 60 days, regardless of
      whether it was a simple or complex gastroschisis, (OR= 3.8; p = 0.021). A complex
      gastroschisis was a risk factor for significantly longer parenteral feedings,
      regardless of the center where patient is treated (Beta = -0.3, p = 0.035).
      CONCLUSIONS: Future research should focus on decisions about delivery timing by
      incorporating risk of neonatal morbidity.

PMID- 27892788
TI  - Vitamin A deficiency due to bi-allelic mutation of RBP4: There's more to it than
      meets the eye.
AB  - Vitamin A deficiency is the leading cause of preventable blindness in children
      worldwide and results in a well-recognized ocular phenotype. Herein we describe a
      patient presenting to the eye clinic with a retinal dystrophy and ocular
      colobomata. This combination of clinical signs and consanguineous pedigree
      structure suggested a genetic basis for the disease, a hypothesis that was tested
      using whole genome sequencing. Bi-allelic mutations in RBP4 were identified
      (c.248+1G>A), consistent with a diagnosis of inherited vitamin A deficiency. We
      describe a constellation of signs that appear to be characteristic for this
      disease, increasing clinical awareness of this rare condition.

PMID- 27892789
TI  - 4-Vinylcyclohexene diepoxide disrupts sperm characteristics, endocrine balance
      and redox status in testes and epididymis of rats.
AB  - OBJECTIVES: Exposure to 4-vinylcyclohexene diepoxide (VCD) was reported to induce
      testicular germ cell toxicity in rodents. However, there is paucity of
      information on the precise biochemical and molecular mechanisms of VCD-induced
      male reproductive toxicity. METHODOLOGY: This study investigated the influence of
      VCD on testicular and epidydimal functions following oral exposure of Wistar rats
      to VCD at 0, 100, 250 and 500 mg/kg for 28 consecutive days. RESULTS:
      Administration of VCD significantly decreased the body weight gain and organo
      somatic indices of the testes and epididymis. When compared with the control, VCD
      significantly decreased superoxide dismutase and catalase activities in the
      testes whereas it significantly decreased superoxide dismutase activity but
      increased catalase activity in the epididymis. Moreover, while glutathione
      peroxidase activity and glutathione level remain unaffected, exposure of rats to
      VCD significantly increased glutathione S-transferase activity as well as
      hydrogen peroxide and malondialdehyde levels in testes and epididymis of the
      treated rats. The spermiogram of VCD-treated rats showed significant decrease in
      epididymal sperm count, sperm progressive motility, testicular sperm number and
      daily sperm production when compared with the control. Administration of VCD
      significantly decreased circulatory concentrations of follicle-stimulating
      hormone, luteinizing hormone and testosterone along with testicular and
      epididymal degeneration in the treated rats. Immunohistochemical analysis showed
      significantly increased cyclooxygenase-2, inducible nitric oxide synthase,
      caspase-9 and caspase-3 protein expressions in the testes of VCD-treated rats.
      CONCLUSION: Exposure to VCD induces testicular and epidydimal dysfunctions via
      endocrine suppression, disruption of antioxidant enzymes activities, increase in
      biomarkers of oxidative stress, inflammation and apoptosis in rats.

PMID- 27892790
TI  - LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent
      to tumor in association with mortality.
AB  - Aberrant DNA methylation seems to be associated with prostate cancer behavior. We
      investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue
      adjacent to tumor (NTAT) in association with mortality from prostate cancer. We
      selected 157 prostate cancer patients with available NTAT from 2 cohorts of
      patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An
      association between LINE-1 hypomethylation and prostate cancer mortality in tumor
      was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40,
      95% confidence interval (CI): 0.95-2.01]. After stratification of the patients
      for Gleason score, the association was present only for those with a Gleason
      score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation
      was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1
      methylation in the NTAT was not associated with prostate cancer mortality. Our
      results are consistent with the hypothesis that tumor tissue global
      hypomethylation may be a late event in prostate cancerogenesis and is associated
      with tumor progression.

PMID- 27892791
TI  - Cardiovascular profile score as a predictor of acute intrapartum non-reassuring
      fetal status in infants with congenital heart defects.
AB  - OBJECTIVES: To investigate the predictive factors of urgent cesarean delivery
      (CD) due to acute intrapartum non-reassuring fetal status (NRFS) in infants with
      congenital heart defects (CHDs). STUDY DESIGN: This was a retrospective review of
      199 singletons prenatally diagnosed with a CHD and for whom vaginal delivery was
      attempted in our institution between 2007 and 2014. A cardiovascular profile
      (CVP) score was used to assess fetal heart failure. RESULTS: The number of urgent
      CDs due to NRFS was 37 (18.6%). Fetuses with a CVP score <=7 were significantly
      more likely to require urgent CD due to NRFS than those with a CVP score >=8 (p <
      0.001). Infants with right heart defects or biventricular cyanotic heart defects
      had a significantly higher frequency of urgent CD due to NRFS than those with
      other types of CHD (p = 0.017). Multivariate analysis showed that a CVP score
      <=7, a birth weight <2500 g, and primipara status were significant predictors of
      urgent CD due to NRFS. CONCLUSIONS: Fetal heart failure, low birth weight, and
      primipara status were revealed to be independent predictors of urgent CD due to
      acute intrapartum NRFS in CHD infants. The CVP score may be a useful
      echocardiographic marker in perinatal management planning.

PMID- 27892792
TI  - E2fl1 is a meiosis-specific transcription factor in the protist Tetrahymena
      thermophila.
AB  - Members of the E2F family of transcription factors have been reported to regulate
      the expression of genes involved in cell cycle control, DNA replication, and DNA
      repair in multicellular eukaryotes. Here, E2FL1, a meiosis-specific E2F
      transcription factor gene, was identified in the model ciliate Tetrahymena
      thermophila. Loss of this gene resulted in meiotic arrest prior to anaphase I.
      The cytological experiments revealed that the meiotic homologous pairing was not
      affected in the absence of E2FL1, but the paired homologous chromosomes did not
      separate and assumed a peculiar tandem arrangement. This is the first time that
      an E2F family member has been shown to regulate meiotic events. Moreover, BrdU
      incorporation showed that DSB processing during meiosis was abnormal upon the
      deletion of E2FL1. Transcriptome sequencing analysis revealed that E2FL1 knockout
      decreased the expression of genes involved in DNA replication and DNA repair in
      T. thermophila, suggesting that the function of E2F is highly conserved in
      eukaryotes. In addition, E2FL1 deletion inhibited the expression of related
      homologous chromosome segregation genes in T. thermophila. The result may explain
      the meiotic arrest phenotype at anaphase I. Finally, by searching for E2F DNA
      binding motifs in the entire T. thermophila genome, we identified 714 genes
      containing at least one E2F DNA-binding motif; of these, 235 downregulated
      represent putative E2FL1 target genes.

PMID- 27892793
TI  - Physiologically-based modeling to predict the clinical behavior of monoclonal
      antibodies directed against lymphocyte antigens.
AB  - Many clinically approved and investigational monoclonal antibody (mAb)-based
      therapeutics are directed against proteins located in the systemic circulation,
      including cytokines, growth factors, lymphocyte proteins, and shed antigens.
      Interaction between mAb and target may lead to non-linear pharmacokinetics (PK),
      characterized by rapid, target-mediated elimination. Several groups have reported
      that determinants of target-mediated elimination could include mAb-target
      binding, target expression, and target turnover. Recently, we scaled a
      physiologically-based pharmacokinetic model for mAb disposition to man and used
      it to predict the non-linear PK of mAbs directed against tumor epithelial
      proteins. In this work, we extended the previously described model to account for
      the influence of lymphocyte proteins on mAb PK in man. To account for the dynamic
      behavior of lymphocytes in the circulation, lymphocyte cycling between blood and
      lymphoid organs was described using first-order transfer rate constants. Use of
      lymphocyte cycling and reported target turnover rates in the model allowed the
      accurate prediction of the pharmacokinetics and pharmacodynamics (PD) of 4 mAbs
      (TRX1, MTRX1011a, rituximab, daclizumab) directed against 3 lymphocyte targets
      (CD4, CD20, CD25). The results described here suggest that the proposed model
      structure may be useful in the a priori prediction of the PK/PD properties of
      mAbs directed against antigens in the circulation.

PMID- 27892795
TI  - Using Emotionally Focused Therapy to Treat Sexual Desire Discrepancy in Couples.
AB  - Couples in committed relationships encounter a multitude of issues. According to
      Metz and McCarthy (2010), when couples report high sexual satisfaction, it
      accounts for 15% to 20% of their overall relationship satisfaction. However, when
      couples report low sexual satisfaction, it contributes 50% to 70% of their
      overall satisfaction with their partner. Issues of sexual desire, currently
      referred to as sexual desire discrepancy, are among the most difficult to treat.
      Although there are many factors contributing to the issue of sexual desire
      discrepancy, current literature highlights the importance of emotional intimacy
      as an outcome and predictor of increased sexual desire. Given the complex nature
      of sexual desire, clinicians often lack the understanding and treatment options
      that are systemic. By viewing sexual desire discrepancy as a relational problem
      that can be treated using emotionally focused therapy, clinicians are better
      equipped to work with emotional and sexual factors that impact desire and couple
      distress.

PMID- 27892794
TI  - Effects of repeated 9 and 30-day exposure to extremely low-frequency
      electromagnetic fields on social recognition behavior and estrogen receptors
      expression in olfactory bulb of Wistar female rats.
AB  - OBJECTIVE: We investigated the short- and long-term effects of extremely low
      frequency electromagnetic fields (EMF) on social recognition behavior and
      expression of alpha- and beta-estrogen receptors (ER). METHODS: Rats were exposed
      to 60-Hz electromagnetic fields for 9 or 30 days and tested for social
      recognition behavior. Immunohistochemistry and western blot assays were performed
      to evaluate alpha- and beta-ER expression in the olfactory bulb of intact,
      ovariectomized (OVX), and ovariectomized+estradiol (E2) replacement (OVX+E2).
      RESULTS: Ovariectomization showed impairment of social recognition after 9 days
      of EMF exposure and a complete recovery after E2 replacement and so did those
      after 30 days. Short EMF exposure increased expression of beta-ER in intact, but
      not in the others. Longer exposure produced a decrease in intact but an increase
      in OVX and OVX+E2. DISCUSSION: Our findings suggest a significant role for beta
      estrogen receptors and a lack of effect for alpha-estrogen receptors on a social
      recognition task. ABBREVIATIONS: EMF: extremely low frequency electromagnetic
      fields; ERs: estrogen receptors; OB: olfactory bulb; OVX: ovariectomized; OVX +
      E2: ovariectomized + estradiol replacement; IEI: interexposure interval; beta-ER:
      beta estrogen receptor; E2: replacement of estradiol; GAPDH: glyceraldehyde-3
      phosphate dehydrogenase; WB: Western blot; PBS: phosphate-buffer saline; PB:
      phosphate-buffer.

PMID- 27892796
TI  - Using a divided-attention stepping accuracy task to improve balance and
      functional outcomes in an individual with incomplete spinal cord injury: A case
      report.
AB  - A spinal cord injury (SCI) frequently results in impaired balance, endurance, and
      strength with subsequent limitations in functional mobility and community
      participation. The purpose of this case report was to implement a training
      program for an individual with a chronic incomplete SCI using a novel divided
      attention stepping accuracy task (DASAT) to determine if improvements could be
      made in impairments, activities, and participation. The client was a 51-year-old
      male with a motor incomplete C4 SCI sustained 4 years prior. He presented with
      decreased quality of life (QOL) and functional independence, and deficits in
      balance, endurance, and strength consistent with central cord syndrome. The
      client completed the DASAT intervention 3 times per week for 6 weeks. Each
      session incorporated 96 multi-directional steps to randomly-assigned targets in
      response to 3-step verbal commands. QOL, measured using the SF-36, was generally
      enhanced but fluctuated. Community mobility progressed from close supervision to
      independence. Significant improvement was achieved in all balance scores: Berg
      Balance Scale by 9 points [Minimal Detectable Change (MDC) = 4.9 in elderly];
      Functional Reach Test by 7.62 cm (MDC = 5.16 in C5/C6 SCI); and Timed Up-and-Go
      by 0.53 s (MDC not established). Endurance increased on the 6-Minute Walk Test,
      with the client achieving an additional 47 m (MDC = 45.8 m). Lower extremity
      isokinetic peak torque strength measures were mostly unchanged. Six minutes of
      DASAT training per session provided an efficient, low-cost intervention utilizing
      multiple trials of variable practice, and resulted in better performance in
      activities, balance, and endurance in this client.

PMID- 27892797
TI  - NEK8 regulates DNA damage-induced RAD51 foci formation and replication fork
      protection.
AB  - Proteins essential for homologous recombination play a pivotal role in the repair
      of DNA double strand breaks, DNA inter-strand crosslinks and replication fork
      stability. Defects in homologous recombination also play a critical role in the
      development of cancer and the sensitivity of these cancers to chemotherapy.
      RAD51, an essential factor for homologous recombination and replication fork
      protection, accumulates and forms immunocytochemically detectable nuclear foci at
      sites of DNA damage. To identify kinases that may regulate RAD51 localization to
      sites of DNA damage, we performed a human kinome siRNA library screen, using DNA
      damage-induced RAD51 foci formation as readout. We found that NEK8, a NIMA family
      kinase member, is required for efficient DNA damage-induced RAD51 foci formation.
      Interestingly, knockout of Nek8 in murine embryonic fibroblasts led to cellular
      sensitivity to the replication inhibitor, hydroxyurea, and inhibition of the ATR
      kinase. Furthermore, NEK8 was required for proper replication fork protection
      following replication stall with hydroxyurea. Loading of RAD51 to chromatin was
      decreased in NEK8-depleted cells and Nek8-knockout cells. Single-molecule DNA
      fiber analyses revealed that nascent DNA tracts were degraded in the absence of
      NEK8 following treatment with hydroxyurea. Consistent with this, Nek8-knockout
      cells showed increased chromosome breaks following treatment with hydroxyurea.
      Thus, NEK8 plays a critical role in replication fork stability through its
      regulation of the DNA repair and replication fork protection protein RAD51.

PMID- 27892799
TI  - Antiviral treatment of HBV positive pregnant women: an additional tool to reduce
      perinatal transmission.

PMID- 27892798
TI  - Transmissibility of Gerstmann-Straussler-Scheinker syndrome in rodent models: New
      insights into the molecular underpinnings of prion infectivity.
AB  - Prion diseases, or transmissible spongiform encephalopathies, have revealed the
      bewildering phenomenon of transmissibility in neurodegenerative diseases. Hence,
      the experimental transmissibility of prion-like neurodegenerative diseases via
      template directed misfolding has become the focus of intense research. Gerstmann
      Straussler-Scheinker disease (GSS) is an inherited prion disease associated with
      mutations in the prion protein gene. However, with the exception of a few GSS
      cases with P102L mutation characterized by co-accumulation of protease-resistant
      PrP core (PrPres) of ~21 kDa, attempts to transmit to rodents GSS associated to
      atypical misfolded prion protein with ~8 kDa PrPres have been unsuccessful. As a
      result, these GSS subtypes have often been considered as non-transmissible
      proteinopathies rather than true prion diseases. In a recent study we inoculated
      bank voles with GSS cases associated with P102L, A117V and F198S mutations and
      found that they transmitted efficiently and produced distinct pathological
      phenotypes, irrespective of the presence of 21 kDa PrPres in the inoculum. This
      study demonstrates that GSS is a genuine prion disease characterized by both
      transmissibility and strain variation. We discuss the implications of these
      findings for the understanding of the heterogeneous clinic-pathological
      phenotypes of GSS and of the molecular underpinnings of prion infectivity.

PMID- 27892800
TI  - What Do Married Couples Think About Induced Abortion?
AB  - This study examined the opinions of married couples concerning induced abortion
      in a sample of 674 married couples obtaining services at a large
      obstetrical/gynecological outpatient service. Although approximately half of the
      sample were not using birth control, a similar percentage felt that curettage
      (selective abortion) should never be performed. A larger percentage felt that
      selective abortion is a sin and should be banned. Sex differences in attitudes
      were minimal. Couples may benefit from a birth control education program in a
      hospital that is designed to cover abortion in order to provide accurate
      information in a more professional environment.

PMID- 27892801
TI  - Stability and migration across femoral varus derotation osteotomies in children
      with neuromuscular disorders.
AB  - Background and purpose - Studies have indicated that one-third of children with
      cerebral palsy (CP) develop dislocation of the hip that needs surgical
      intervention. When hip dislocation occurs during childhood surgical treatment
      consists of tenotomies, femoral varus derotation osteotomy (VDRO), and
      acetabuloplasty. Relapse is observed in one-fifth of cases during adolescence. In
      this prospective cohort study, we performed a descriptive evaluation of
      translation and rotation across VDROs in children with neuromuscular disorders
      and syndromes by radiostereometric analysis (RSA). We assessed "RSA stability"
      and migration across the VDROs. Patients and methods - Children with a
      neuromuscular disorder were set up for skeletal corrective surgery of the hip.
      RSA follow-ups were performed postoperatively, at 5 weeks, and 3, 6, and 12
      months after surgery. Results - 27 femoral VDROs were included; 2 patients were
      excluded during the study period. RSA data showed stability across the VDRO in
      the majority of cases within the first 5 weeks. At the 1-year follow-up, the mean
      translations (SD) of the femoral shaft distal to the VDRO were 0.51 (1.12) mm
      medial, 0.69 (1.61) mm superior, and 0.21 (1.28) mm posterior. The mean rotations
      were 0.39 degrees  (2.90) anterior tilt, 0.02 degrees  (3.07) internal rotation,
      and 2.17 degrees  (2.29) varus angulation. Interpretation - The migration
      stagnates within the first 5 weeks, indicating stability across the VDRO in most
      patients.

PMID- 27892802
TI  - Longitudinal changes and correlations of bioimpedance and anthropometric
      measurements in pregnancy: Simple possible bed-side tools to assess pregnancy
      evolution.
AB  - PURPOSE: The aim of this study was to assess longitudinal changes of bioimpedance
      analysis compared with anthropometric measurements in low-risk pregnant woman
      recruited in the first trimester and to observe possible differences in these
      indices in women who developed high-risk pregnancies. MATERIALS AND METHODS:
      Bioimpedance indices for the three trimesters of pregnancies were calculated
      separately for uneventful pregnancies delivered of newborns > the 10th centile.
      These findings were compared with anthropometric measurements. Data of women who
      developed hypertensive disorders of pregnancy (HDP) or delivered SGA newborns
      were calculated and compared. RESULTS: Significantly longitudinal increases were
      observed in these pregnancies for total body water (TBW), free fat mass, fat
      mass, and extra-cellular water. These increases were paralleled body mass index
      (BMI), skinfolds, and waist measurements. The correlations between these two sets
      of findings were poor. Women who developed HDP with AGA fetuses showed
      significantly different bioimpedance from normal cases. TBW indices were highly
      significantly different since the first trimester. In pregnancies delivered of
      SGA newborns, these indices were opposite of the values observed in patients with
      HDP-AGA, TBW in these patients was significantly reduced compared with normal
      pregnancies. CONCLUSIONS: The bioelectrical impedance is a fast, simple,
      noninvasive way to assess the TBW content in pregnancy. Our findings are in
      agreement with the hypothesis that bioimpedance might help to identify early in
      gestation patients at risk of developing different clinical phenotypes of
      hypertensive disease of pregnancy and SGA fetuses.

PMID- 27892803
TI  - Attitudes of Heterosexual Men and Women Toward HIV Negative and Positive Gay Men.
AB  - Attitudes of Italian heterosexual men and women toward gay men, both HIV positive
      and negative, are poorly investigated. Italian culture is still extremely
      conservative and provides limited support to the gay community (e.g., lack of
      same-sex marriage recognition). Consequently, gay men experience social exclusion
      and disparities. The present study explores the association between homophobia
      and closeness with sexual orientation and HIV status. 261 heterosexual Italian
      men and women were assessed for feelings of closeness and homophobia after
      reading a vignette where the character was C1: heterosexual and HIV negative; C2:
      gay and HIV negative; or C3: gay and HIV positive. Experiences of homophobia and
      closeness varied depending on gender of participant and condition assigned, and
      higher levels of homophobia were correlated with lower levels of closeness
      regardless of HIV status. Implications and future directions are discussed.

PMID- 27892804
TI  - The form of the story: Measuring formal aspects of narrative activity in
      psychotherapy.
AB  - OBJECTIVE: We ask which are the clinically relevant qualities of narratives in
      psychotherapy and how they can be measured. METHOD: On the background of
      psychoanalytic assumptions and narrative theory, we propose to measure formal
      narrative processes which stay close to the linguistic surface, because these
      escape conscious control. RESULTS: We propose five aspects of narratives to be
      especially sensitive to distortions and therefore prone to change in successful
      therapies: (1) The actual chronological, stepwise narrating of events, (2) the
      intentional structuring of events, or emplotment, (3) the immediate evaluation,
      (4) the reflected interpretation of events, and finally (5) the consistency and
      completeness of the narrative. For each aspect we discuss ways to measure them.
      Finally the aspects are illustrated with excerpts from a series of diagnostic
      interviews. DISCUSSION: Implications for the analysis of the co-narrative role of
      the therapist are suggested.

PMID- 27892805
TI  - Addressing the needs of Nicaraguan older adults living on the edge: A university
      community partnership in international service-learning.
AB  - Nicaragua is a very low-income country entering a period of rapid aging with
      limited geriatric training for health care professionals. To help build capacity
      and to enhance student learning, a short-term international service-learning
      program was implemented in 2004 in partnership with the Jessie F. Richardson
      Foundation and Nicaraguan community stakeholders. Graduate and undergraduate
      students at Portland State University complete coursework for one term in the
      United States then travel to Nicaragua for about two weeks to participate in
      educational, research, and service activities, primarily in group homes for older
      Nicaraguans. Students learn about global aging, gerontology, community
      development, service learning, and Nicaraguan history and culture, then apply
      their gerontology-related knowledge by training direct care staff, older adults
      and their family members, and students. The authors describe the impetus for and
      evolution of the program, students' evaluation of the program, faculty
      observations on program benefits and challenges, lessons learned, and future
      plans.

PMID- 27892806
TI  - Wisconsin Card Sorting Test embedded validity indicators developed for adults can
      be extended to children.
AB  - Past studies have examined the ability of the Wisconsin Card Sorting Test (WCST)
      to discriminate valid from invalid performance in adults using both individual
      embedded validity indicators (EVIs) and multivariate approaches. This study is
      designed to investigate whether the two most stable of these indicators-failures
      to maintain set (FMS) and the logistical regression equation S-BLRE-can be
      extended to pediatric populations. The classification accuracy for FMS and S-BLRE
      was examined in a mixed clinical sample of 226 children aged 7 to 17 years (64.6%
      male, MAge = 13.6 years) against a combination of established performance
      validity tests (PVTs). The results show that at adult cutoffs, FMS and S-BLRE
      produce an unacceptably high failure rate (33.2% and 45.6%) and low specificity
      (.55-.72), but an upward adjustment in cutoffs significantly improves
      classification accuracy. Defining Pass as <2 and Fail as >=4 on FMS results in
      consistently good specificity (.89-.92) but low and variable sensitivity (.00
      .33). Similarly, cutting the S-BLRE distribution at 3.68 produces good
      specificity (.90-.92) but variable sensitivity (.06-.38). Passing or failing FMS
      or S-BLRE is unrelated to age, gender and IQ. The data from this study suggest
      that in a pediatric sample, adjusted cutoffs on the FMS and S-BLRE ensure good
      specificity, but with low or variable sensitivity. Thus, they should not be used
      in isolation to determine the credibility of a response set. At the same time,
      they can make valuable contributions to pediatric neuropsychology by providing
      empirically-supported, expedient and cost-effective indicators to enhance
      performance validity assessment.

PMID- 27892807
TI  - The effect of early life stress on the cognitive phenotype of children with an
      extra X chromosome (47,XXY/47,XXX).
AB  - Studies on gene-environment interactions suggest that some individuals may be
      more susceptible to life adversities than others due to their genetic profile.
      This study assesses whether or not children with an extra X chromosome are more
      vulnerable to the negative impact of early life stress on cognitive functioning
      than typically-developing children. A total of 50 children with an extra X
      chromosome and 103 non-clinical controls aged 9 to 18 years participated in the
      study. Cognitive functioning in domains of language, social cognition and
      executive functioning were assessed. Early life stress was measured with the
      Questionnaire of Life Events. High levels of early life stress were found to be
      associated with compromised executive functioning in the areas of mental
      flexibility and inhibitory control, irrespective of group membership. In
      contrast, the children with an extra X chromosome were found to be
      disproportionally vulnerable to deficits in social cognition on top of executive
      dysfunction, as compared to typically-developing children. Within the extra X
      group the number of negative life events is significantly correlated with more
      problems in inhibition, mental flexibility and social cognition. It is concluded
      that children with an extra X chromosome are vulnerable to adverse life events,
      with social cognition being particularly impacted in addition to the negative
      effects on executive functioning. The findings that developmental outcome is
      codependent on early environmental factors in genetically vulnerable children
      also underscores opportunities for training and support to positively influence
      the course of development.

PMID- 27892809
TI  - Civil capacity in transition-age youth with history of central nervous system
      compromise: a review.
AB  - OBJECTIVE: The purpose of this paper is to review various aspects of decision
      making capacities in children and adolescents with a history of central nervous
      system compromise over the course of development and into transition to
      adulthood. METHOD: The literature on consent capacity in various domains is
      reviewed, with reference to state-specific legal definitions and requirements,
      and illustrated with a case example. CONCLUSIONS: Neuropsychologists who use an
      evidence-based assessment approach, and who can clearly communicate their
      findings in reference to specific probate court standards, can make a unique
      contribution to the legal system while serving their clients who are
      transitioning from adolescence into adulthood.

PMID- 27892808
TI  - Self-reported impulsivity in Huntington's disease patients and relationship to
      executive dysfunction and reward responsiveness.
AB  - INTRODUCTION: Few studies have directly investigated impulsivity in Huntington's
      disease (HD) despite known changes in dopaminergic and frontal functioning,
      changes that have been associated with impulsivity in other disorders and in the
      normal population. This study sought to further categorize impulsivity in HD
      through examining differences in self-reported impulsivity between community
      controls and HD patients, the relationship between executive dysfunction and
      impulsivity, and the relationship of a reward/punishment behavioral inhibition
      task in relation to these self-report measures. It was expected that HD patients
      would report higher impulsivity and executive dysfunction and that these measures
      would relate to a reward/punishment behavioral inhibition task. METHOD: The
      Barratt Impulsivity Scale (BIS-11) and Behavioral Inhibition/Behavioral
      Activation Scale (BIS/BAS) were completed, and the Mini-Mental State Examination
      (MMSE) and a reward-based flanker task with punishing and rewarding conditions
      were administered to 22 HD patients and 14 control participants. RESULTS: HD
      patients reported higher trait impulsivity (BIS-11) and executive dysfunction
      (Frontal Systems Behavior Scale, FrSBE) but not increased impulsivity on the
      BIS/BAS relative to controls. Higher BIS-11 scores were related to increased self
      reported executive dysfunction and the attention/working memory factor of the
      MMSE. On a reward/punishment behavioral inhibition task, BAS was uniquely related
      to increased accuracy on rewarding trials of the flanker task, but was not
      related to punishing trials in HD patients. CONCLUSIONS: The relationships found
      suggest that trait impulsivity is reported higher in HD and may not be driven by
      altered reward evaluation and the appetitive nature of stimuli but rather by
      increased executive dysfunction and lack of sensitivity to punishment.
      Impulsivity in HD may represent a combination of trait impulsivity, altered
      dopaminergic circuitry, and executive dysfunction. Understanding impulsivity in
      HD is important as it is related to increased risk to the patient and difficult
      behaviors for the caregiver, and sheds light on the disease process.

PMID- 27892811
TI  - Simultaneous determination of glycyrrhizin and liquiritin in licorice roots and
      Kampo medicines by combination enzyme-linked immunosorbent assay using anti
      glycyrrhizin and anti-liquiritin monoclonal antibodies.
AB  - Immunoassay systems using monoclonal antibodies (mAbs) are one of the most useful
      techniques in the analytical, biochemical, and clinical fields. In this study, a
      combination enzyme-linked immunosorbent assay (ELISA) using both anti
      glycyrrhizin and anti-liquiritin mAbs (anti-GL/Liq mixture mAbs) was developed
      for quality control of licorice and its products. The combination ELISA
      demonstrated high sensitivity, reproducibility, and specificity for the total
      content of GL and Liq by a single assay. The developed ELISA was effective and
      useful as the first screening method in the selection of high-quality licorice
      from the Glycyrrhiza species and in confirming the quality of licorice-containing
      Kampo medicines.

PMID- 27892812
TI  - Satisfaction of Nigerian stroke survivors with outpatient physiotherapy care.
AB  - OBJECTIVE: To investigate the satisfaction of stroke survivors with outpatient
      physiotherapy care. METHODS: Sixty stroke survivors were surveyed using the
      European Physiotherapy Treatment Outpatient Satisfaction Survey (EPTOPS). Focus
      group discussion (FGD) was also conducted with four stroke survivors from the
      same sample. Data were analyzed using the Kruskal Wallis test and Spearman's
      correlation coefficients at p = 0.05. FGD was transcribed and thematically
      analyzed. RESULTS: Nearly all the participants (98.3%) indicated one of good,
      very good, and excellent improvement in their clinical conditions with
      physiotherapy. Majority expressed satisfaction with their physiotherapy care, the
      modal response being very good (59.3%). Patients' satisfaction and socio
      demographics were not significantly correlated (p > 0.05). Overarching themes
      from FGD were physiotherapy in stroke rehabilitation, satisfaction with
      physiotherapy care, cost, and lack of continuity of care as sources of
      dissatisfaction. Physiotherapists' demeanor was a facilitator of satisfaction.
      CONCLUSION: The stroke survivors were generally satisfied with outpatient
      physiotherapy care. However, lack of continuity and cost of care were sources of
      dissatisfaction among patients. Delivery of physiotherapy to stroke survivors in
      Nigeria should be structured to allow for continuity of care as this may enhance
      satisfaction. Implementation of inexpensive rehabilitation strategies may help
      reduce cost of physiotherapy.

PMID- 27892814
TI  - A new route of bioaugmentation by allochthonous and autochthonous through biofilm
      bacteria for soluble chemical oxygen demand removal of old leachate.
AB  - Landfill leachate contains environmental pollutants that are generally resistant
      to biodegradation. In this study, indigenous and exogenous bacteria in leachate
      were acclimated in both biofilm and suspension forms to increase the removal of
      soluble chemical oxygen demand (SCOD). The bacteria from the leachate and sewage
      were acclimated to gradually increasing leachate concentration prepared using a
      reverse osmosis membrane over 28 days. The SCOD removal was measured aerobically
      or nominally anaerobically. Biofilms were prepared using different carrier media
      (glass, rubber, and plastic). The maximum SCOD removal in suspensions was 32%
      (anaerobic) and in biofilms was 39% (aerobic). In the suspension form, SCOD
      removal using acclimated bacteria from leachate and sewage anaerobically
      increased in comparison with the control (P < .05). In the biofilm form, the
      aerobic condition and the use of acclimated bacteria from leachate and sewage
      increased the removal efficiency of SCOD in comparison with other biofilm groups
      (P < .05). Three species of bacteria, including Bacillus cereus, Bacillus
      subtilis, and Pseudomonas aeruginosa were identified in the biofilm from leachate
      and sewage. Bioaugmentation technology using biofilms and acclimations can be an
      effective, inexpensive, and simple way to decrease SCOD in old landfill leachate.

PMID- 27892813
TI  - Thinking about social and nonsocial alternative possibilities in premature
      preschoolers.
AB  - INTRODUCTION: Prematurely born preschoolers show developmental cognitive delay
      compared to full-term children. There are important neurological networks
      developing at preschool age related to perspective taking about the attribution
      of belief and to deduction with contrary-to-fact situations. Other deductive
      abilities may be completed during that period. METHOD: A group of very
      prematurely born children (N = 35) aged between 4 and 5 years was compared with a
      control group of children born at full term (N = 35). They completed different
      cognitive tasks that required making inferences about possible true facts and
      false facts, and about others' beliefs. RESULTS: Results showed that preterm
      children had more difficulties with false beliefs and counterfactual tasks than
      the controls but they did not differ in equivalent deductive tasks. CONCLUSIONS:
      We discuss the possible difficulties of preterm children when they first reach
      primary school age, not only with social perspective taking, but also with
      considering nonsocial contrary-to-fact alternatives. Prematurity is not a
      syndrome, but could be a risk condition. Therefore, these results are relevant in
      the field of differential diagnosis-in particular, for children with difficulties
      in perspective taking, a condition with which children born prematurely could
      share some characteristics.

PMID- 27892815
TI  - Monitoring trihalomethanes and nitrogenous disinfection by-products in blending
      desalinated waters using solid-phase microextraction and gas chromatography.
AB  - A simple and efficient method has been developed for the extraction and
      determination of 16 common volatile halogenated disinfection by-products (DBPs)
      (four trihalomethanes, six haloacetonitriles, and six halonitromethanes) in
      blending desalinated waters, using headspace solid-phase microextraction and gas
      chromatography with flame ionization detector (HS-SPME/GC-FID). After the
      optimization using factorial designs of the HS-SPME parameters (optimum:
      carboxen/polydimethylsiloxane such as fiber, extraction time of 60 min at 30
      degrees C, pH 7, addition of 40% (w/v) of sodium chloride, and desorption time of
      2 min at 250 degrees C), quantification limits ranged from 3.03 to 40.8 ug L-1,
      and relative standard deviation (inter-day) were lower than 9.7% for all the
      target DBPs. Adequate relative recoveries (with the exception of
      chloronitromethane) were obtained even when spiking waters at low levels (25 ug L
      1), with values between 83.1% and 119% for ultrapure water, and between 87.4% and
      115% for blending desalinated waters, supporting in this way the applicability of
      the method. The influence of various dechlorinating agents on the stability of 16
      DBPs in water was evaluated, with ammonium chloride being the most suitable
      inhibitor of residual chlorine and carrying out the analytical determination of
      DBPs within 48 h after sampling. Different blending desalinated water samples
      collected in the South of Tenerife Island (Spain) were successfully analyzed.

PMID- 27892816
TI  - Optimization of the pretreatment of wastewater from a slaughterhouse and packing
      plant through electrocoagulation in a batch reactor.
AB  - The purpose of this study is to evaluate the removal of chemical oxygen demand
      (COD), turbidity and color of wastewater from a pig slaughterhouse and packing
      plant through the electrochemical technique and to optimize the DeltaV (electric
      potential difference) and HRT (hydraulic retention time) variables in an
      electrocoagulation batch reactor using aluminum electrodes. The experimental
      design used was rotatable central composite design. For turbidity, the values for
      removal efficiency obtained varied from 92.85% to 99.28%; for color, they varied
      from 81.34% to 98.93% and for COD, they varied from 58.61% to 81.01%. The best
      optimized conditions of treatment were at 25 min for the HRT and 25 V for the
      DeltaV, which correspond to electrical current of 1.08 A and a current density of
      21.6 mA cm-2. The aluminum residue varied from 15.254 to 54.291 mg L-1 and the
      cost of the treatment was US$4.288 m-3. The novelty of the work was the
      simultaneous optimization of three response variables using the desirability
      function applied to the treatment of wastewater from slaughterhouses.

PMID- 27892817
TI  - Creating the medical school of the future through incremental curricular
      transformation: the Stanford Healthcare Innovations and Experiential Learning
      Directive (SHIELD).

PMID- 27892818
TI  - Interaction of stattic, a STAT3 inhibitor with human serum albumin: spectroscopic
      and computational study.

PMID- 27892819
TI  - Fear generalisation in individuals with high neuroticism: increasing
      predictability is not necessarily better.
AB  - Fear generalisation, a process by which conditioned fear spreads to similar but
      innocuous stimuli, is key in understanding why some individuals feel unsafe in
      objectively non-threatening situations. Both trait neuroticism and lack of
      predictability about the likelihood of feared consequences are associated with
      negative affect in the face of ambiguity and may increase the degree to which
      fear generalises. Undergraduates (N = 129) with varying degrees of neuroticism
      were randomised to either high- or low-instructional predictability conditions
      prior to fear acquisition. A fear generalisation test measured risk ratings and
      attentional bias on a modified dot-probe paradigm. Among individuals with higher
      neuroticism, providing instructional predictability did not reduce fear; these
      individuals reported higher risk and increased attentional bias toward ambiguous
      stimuli. Overall, for individuals with higher neuroticism, predictability
      information hurt rather than helped interpretation of ambiguous stimuli,
      challenging a common conceptualisation of predictability as a factor that reduces
      fear.

PMID- 27892820
TI  - Addressing adolescents' risk and protective factors related to risky behaviours:
      Findings from a school-based peer-education evaluation in the Western Cape.
AB  - BACKGROUND: Peer-education programmes aim to bring about attitudinal and
      behavioural changes in their target audience. In the South African educational
      context, peer education is a favoured approach in dealing with issues such as HIV
      and AIDS, sexual decision-making and substance misuse. Given the reliance on peer
      education programmes in the educational system, it is important to establish how
      well they are working. This study aims to assess the effect of an extensive,
      structured, time-limited, curriculum-based, peer-led educational programme on
      first-year high school learners in public schools in the Western Cape Province of
      South Africa. METHOD: The curriculum called 'Listen Up' addresses issues such as
      supporting peers, sexual decision-making, healthy relationships, HIV risk,
      alcohol misuse and unwanted pregnancy in seven structured sessions. The programme
      targeted adolescents in Grade 8 growing up in what are considered to be risky
      environments in public schools in the Western Cape during 2012 and 2013. The
      intervention was evaluated based on 10 scales sourced from published literature
      related to the outcome indicators of future orientation, sensation-seeking, self
      efficacy in sexual relations, HIV transmission knowledge, HIV prevention
      knowledge, HIV attitudes, sexual attitudes, decision-making, healthy
      relationships and social support. Descriptive statistics were used to analyse
      demographic and community characteristics and analyses of variance were used to
      detect differences between groups. The surveys were administered to a total of
      7709 learners across three waves of the study in 27 peer intervention schools and
      eight control schools. RESULTS: Immediately post intervention, statistically
      significant differences were noted for the intervention schools when compared to
      their baseline levels on measures of future orientation, self-efficacy in sexual
      relations, knowledge regarding HIV transmission, knowledge regarding HIV
      prevention and knowledge in terms of healthy relationships. Comparing baseline
      values with results collected between five and seven months post intervention,
      statistically significant results were noted for self-efficacy in sexual
      relations and knowledge regarding HIV transmission. CONCLUSION: The findings of
      this study suggest that peer-education can improve adolescents' self-efficacy in
      sexual relations as well as knowledge regarding the transmission of HIV and
      therefore can contribute to the prevention of HIV transmission among adolescents.

PMID- 27892821
TI  - Self-regulation upon return to driving after traumatic brain injury.
AB  - The aim of this study was to explore self-reported driving habits and the factors
      associated with these within the first three months of return to driving
      following traumatic brain injury (TBI). Participants included 24 individuals with
      moderate to severe TBI (post-traumatic amnesia duration M = 33.26, SD = 29.69
      days) and 28 healthy age, education, and gender-matched controls who completed an
      on-road assessment. Driving frequency and avoidance questionnaires were
      administered to assess premorbid driving, anticipated driving upon resuming, and
      driving at three months post-assessment. There were no differences between groups
      for premorbid driving frequency or avoidance. Individuals with TBI anticipated
      greater reductions in driving frequency, t(29.57) =  -3.95, p < .001, and
      increases in avoidance, U = 171.00, z = -2.69, p < .01. On follow up, significant
      reductions in frequency, t(48)  = -3.03, p < .01, but not avoidance, U = 239.00,
      z = -1.35, p = .18, were observed. Females were more likely to reduce their
      driving frequency, rs =  -.43, p < .05, while increased anxiety was associated
      with increased avoidance r = .63, p < .05, and reduced frequency r = -.43, p <
      .05. It was concluded that individuals with TBI anticipated changes in their
      driving habits upon return to driving, indicating an expectation for post-injury
      changes to their driving lifestyle. On follow up, many of these intended changes
      to driving habits, particularly in relation to driving frequency, were reported
      by individuals with TBI, suggestive of some strategic self-regulation.

PMID- 27892822
TI  - The effect of manipulated information about premenstrual changes on the report of
      positive and negative premenstrual changes.
AB  - Although women predominantly report negative premenstrual changes, a substantial
      portion of women also reports positive changes. Little is known about factors
      related to report of positive and negative premenstrual changes. The aim of this
      experimental study at the Philipps-University of Marburg from January and
      February 2015 was to investigate the effect of manipulated information about
      premenstrual changes on the retrospective report of premenstrual changes. A total
      of 241 healthy women were randomly assigned either to an experimental group (EG)
      reading: (1) text focusing on negative and positive premenstrual changes (EG1 (+/
      )); (2) text focusing on negative changes (EG2 (-)); or (3) control group (CG)
      text. At least one positive premenstrual change was reported by the majority of
      the participating women. The results of the MANOVA and discriminant analysis
      showed that, after having read the text, EG2 (-) reported more negative and fewer
      positive premenstrual changes in a retrospective screening compared to EG1 (+/-)
      and CG. No significant difference was observed between EG1 (+/-) and CG. The
      results show the negative influence of information focusing on negative
      premenstrual changes on the retrospective report of both negative and positive
      premenstrual changes.

PMID- 27892823
TI  - Changes in joint range of motion and muscle-tendon unit stiffness after varying
      amounts of dynamic stretching.
AB  - The purpose of this study was to examine the effects of varying amounts of
      dynamic stretching (DS) on joint range of motion (ROM) and stiffness of the
      muscle-tendon unit (MTU). Fifteen healthy participants participated in four
      randomly ordered experimental trials, which involved one (DS1), four (DS4) and
      seven (DS7) sets of DS, or control conditions/seated at rest (CON). Each DS set
      consisted of 15 repetitions of an ankle dorsiflexion-plantarflexion movement. The
      displacement of the muscle-tendon junction (MTJ) was measured using
      ultrasonography while the ankle was passively dorsiflexed at 0.0174 rad . s-1 to
      its maximal dorsiflexion angle. Passive torque was also measured using an
      isokinetic dynamometer. Ankle ROM was significantly increased after DS4 and DS7
      compared with the pre-intervention values (P < 0.05), but there were no
      significant differences in ankle ROM between DS4 and DS7. No differences were
      observed in ankle ROM after DS1 and CON. In addition, the stiffness of the MTU,
      passive torque and displacement of the MTJ at submaximal dorsiflexion angles did
      not change in any of the experimental conditions. These results indicate that DS4
      increased ankle ROM without changing the mechanical properties of the MTU, and
      that this increase in ankle ROM plateaued after DS4.

PMID- 27892824
TI  - Experiences of Korean mothers of children with cancer: A Photovoice study.
AB  - Using Photovoice, a participatory action research methodology, we investigated
      Korean mothers' lives postdiagnosis of their child with cancer. Photovoice was
      used to understand the mothers' perceptions of how they have adapted to their
      children's illnesses. Five mothers of children with cancer participated in five
      sessions of the Photovoice project, during which they took and shared photographs
      and narratives about their experiences and joined weekly group discussions on
      their selected themes. The following themes and subthemes emerged: "What I would
      like to do (taking a break, socializing with friends, spending time with other
      family members, developing my career)," "My child and food (whatever my child
      wants to eat, love of family)," "My days for my child (doing what my child wants
      to do, being a playmate, changing for my child)," and "Power sources for me
      (family, courage of children, mom is strong, hope)." Having a child with cancer
      greatly affects the mother's social and work lives as well as emotional well
      being. Services and programs such as respite care, parenting education, and
      psychological support are recommended based on the study findings.

PMID- 27892825
TI  - Strange Bedfellows: Anachronisms, Identity Politics, and the Queer Case of Trans.
AB  - This article explores trans identities, as articulated within a few historical
      texts. From early literary depictions of gender difference, to medicalized
      conceptions of transsexualism, to a proliferation of trans and queer identities
      represented by an ever-expanding "alphabet soup" of identity labels, our
      understandings of identities, sexualities, and queer community-building continue
      to change. I use the notion of "kind-making," as elaborated on in the work of Ian
      Hacking, to illustrate that some queer and trans identifications are affiliative,
      whereas others are contrastive or oppositional in nature, and these structural
      differences have important implications with respect to understanding identity
      and sexuality, and also trans inclusion within LGBT communities and activist
      efforts.

PMID- 27892826
TI  - Assessing factors associated with HIV testing among adolescents in Malawi.
AB  - Despite being at high risk of HIV/AIDS, most young people do not know their HIV
      status. Using survey data (n = 2428) and applying multilevel models, this paper
      assesses factors associated with HIV testing among adolescents in Northern
      Malawi. The results show that among both boys (OR = 0.39) and girls (OR = 0.47),
      orphan status is associated with low likelihood of HIV testing. Correct knowledge
      about HIV/AIDS (OR = 2.55) and having secondary education (OR = 3.24) are
      associated with HIV testing among boys and girls, respectively. At the household
      level, living in a household whose head has secondary or higher education is
      positively associated with testing for boys (OR = 2.63), while residing together
      with biological siblings predicts higher odds of testing (OR = 2.67) for girls.
      Notably, orphaned girls' disadvantage regarding HIV testing loses significance
      when residential arrangement is controlled. At the community level, having HIV
      testing facility (OR = 2.70) or post-test club (OR = 1.40) is positively
      associated with HIV testing for boys, while girls from areas where religious
      leaders hold judgmental views about HIV/AIDS are less likely (OR = 0.45) to test.
      These findings suggest that efforts to scale up HIV testing among youth could
      benefit greatly from an understanding of how individual and community factors
      operate to influence adolescents to know their sero-status.

PMID- 27892828
TI  - Qualitative and quantitative analysis of monomers in polyesters for food contact
      materials.
AB  - Polyesters (PESs) are gaining more importance on the food contact material (FCM)
      market and the variety of properties and applications is expected to be wide. In
      order to acquire the desired properties manufacturers can combine several FCM
      approved polyvalent carboxylic acids (PCAs) and polyols as monomers. However,
      information about the qualitative and quantitative composition of FCM articles is
      often limited. The method presented here describes the analysis of PESs with the
      identification and quantification of 25 PES monomers (10 PCA, 15 polyols) by HPLC
      with diode array detection (HPLC-DAD) and GC-MS after alkaline hydrolysis.
      Accurate identification and quantification were demonstrated by the analysis of
      seven different FCM articles made of PESs. The results explained between 97.2%
      and 103.4% w/w of the polymer composition whilst showing equal molar amounts of
      PCA and polyols. Quantification proved to be precise and sensitive with
      coefficients of variation (CVs) below 6.0% for PES samples with monomer
      concentrations typically ranging from 0.02% to 75% w/w. The analysis of 15 PES
      samples for the FCM market revealed the presence of five different PCAs and 11
      different polyols (main monomers, co-monomers, non-intentionally added substances
      (NIAS)) showing the wide variety of monomers in modern PESs. The presented method
      provides a useful tool for commercial, state and research laboratories as well as
      for producers and distributors facing the task of FCM risk assessment. It can be
      applied for the identification and quantification of migrating monomers and the
      prediction of oligomer compositions from the identified monomers, respectively.

PMID- 27892827
TI  - Rationale, Procedures, and Response Rates for the 2015 Administration of NCI's
      Health Information National Trends Survey: HINTS-FDA 2015.
AB  - The National Cancer Institute (NCI) developed the Health Information National
      Trends Survey (HINTS) to monitor population trends in cancer communication
      practices, information preferences, health risk behaviors, attitudes, and cancer
      knowledge. The U.S. Food and Drug Administration (FDA) recognized HINTS as a
      unique data resource for informing its health communication endeavors and
      partnered with NCI to field HINTS-FDA 2015. HINTS-FDA 2015 was a self
      administered paper instrument sent by mail May 29 to September 8, 2015, using a
      random probability-based sample of U.S. postal addresses stratified by county
      level smoking rates, with an oversampling of high and medium-high smoking strata
      to increase the yield of current smokers responding to the survey. The response
      rate for HINTS-FDA 2015 was 33% (N = 3,738). The yield of current smokers (n =
      495) was lower than expected, but the sampling strategy achieved the goal of
      obtaining more former smokers (n = 1,132). Public-use HINTS-FDA 2015 data and
      supporting documentation have been available for download and secondary data
      analyses since June 2016 at http://hints.cancer.gov . NCI and FDA encourage the
      use of HINTS-FDA for health communication research and practice related to
      tobacco-related communications, public knowledge, and behaviors as well as
      beliefs and actions related to medical products and dietary supplements.

PMID- 27892829
TI  - Understanding the Sexual Satisfaction of Women With Provoked Vestibulodynia and
      Their Partners: Comparison With Matched Controls.
AB  - Provoked vestibulodynia (PVD)-a recurrent, localized vulvar pain-interferes with
      couples' sexual relationships as evidenced by lower sexual satisfaction compared
      to controls. Little is known about what components of sexual satisfaction
      contribute to this lower satisfaction. Using the Interpersonal Exchange Model of
      Sexual Satisfaction (IEMSS), we compared the sexual exchanges (sexual rewards and
      costs, relative sexual rewards and costs, balance of sexual rewards and costs,
      balance of relative sexual rewards and costs, equality of sexual rewards and
      costs) and sexual satisfaction of 50 women with PVD and their male partners to 50
      matched-control couples. We also compared women with PVD and their partners on
      these same components. Participants completed standardized measures of sexual
      exchanges and sexual satisfaction. Women with PVD and their partners reported
      lower relative sexual rewards, a less favorable balance of relative sexual
      rewards to costs, and lower sexual satisfaction than controls, although
      differences were larger for women. Women with PVD also reported lower levels of
      sexual rewards, higher levels of sexual costs, a less favorable balance of sexual
      rewards to costs, and lower equality of sexual costs, than control women.
      Findings identify IEMSS exchange components that may contribute to overall lower
      satisfaction in couples affected by PVD.

PMID- 27892830
TI  - Risk assessment of plant food supplements and other herbal products containing
      aristolochic acids using the margin of exposure (MOE) approach.
AB  - After the incidences of induction of aristolochic acid nephropathy after
      consumption of herbal weight loss preparations that accidentally contained
      aristolochic acids (AAs), several countries defined national restrictions on the
      presence of AAs in food, including plant food supplements (PFS) and herbal
      products. This study investigates whether the risks associated with exposure to
      AAs via PFS and herbal products are at present indeed negligible. Data reported
      in literature on AA levels in PFS and other herbal products and also obtained
      from a new series of PFS in the present study were used to calculate the
      estimated daily intakes (EDIs) and corresponding margins of exposure (MOEs).
      Available literature data revealed that 206 out of 573 samples were found to
      contain aristolochic acid I (AAI) and/or aristolochic acid II (AAII). The results
      obtained from recently collected PFS revealed that both AAI and AAII were
      detected in three out of 18 analysed PFS at levels up to 594.8 and 235.3 ug g-1,
      respectively, being in line with the levels reported in literature. The EDIs
      resulting from intake of these PFS resulted in MOEs that were generally below
      10,000, corroborating the priority for risk management. Although these results
      refer to PFS collected by targeted sampling strategies, the data reveal that AA
      containing PFS are still freely available. When considering that the use of these
      samples may be limited to shorter periods of time, the EDIs might be lower, but
      MOE values would still be lower than 10,000 for more than 50% of the AA
      containing PFS and herbal products. In conclusion, the presence of AAs in PFS and
      herbal products even several years after instalment of the legal restrictions
      still raises concern, especially for people who frequently use the respective PFS
      and herbal products.

PMID- 27892831
TI  - Who's Afraid of the Beast in the Jamesian Closet?
AB  - Building on the Foucauldian insight that sexuality is a discourse and thereby
      refusing to be chained to the Freudian repressive hypothesis, this article aims
      to ascertain how the closet is made and how the homosexual comes to be seen in
      the act of reading the literary text "The Beast in the Jungle," written by Henry
      James. It will examine the power relationships between the characters and between
      the narrator and the reader, surrounding the protagonist's sexual secret, which
      is linked to fear.

PMID- 27892832
TI  - Pushing and pulling: an assessment tool for occupational health and safety
      practitioners.
AB  - A tool has been developed for supporting practitioners when assessing manual
      pushing and pulling operations based on an initiative by two global companies in
      the manufacturing industry. The aim of the tool is to support occupational health
      and safety practitioners in risk assessment and risk management of pushing and
      pulling operations in the manufacturing and logistics industries. The tool is
      based on a nine-multiplier equation that includes a wide range of factors
      affecting an operator's health risk and capacity in pushing and pulling. These
      multipliers are based on psychophysical, physiological and biomechanical studies
      in combination with judgments from an expert group consisting of senior
      researchers and ergonomists. In order to consider usability, more than 50
      occupational health and safety practitioners (e.g., ergonomists, managers, safety
      representatives and production personnel) participated in the development of the
      tool. An evaluation by 22 ergonomists supports that the push/pull tool is user
      friendly in general.

PMID- 27892833
TI  - A mega-analysis of memory reports from eight peer-reviewed false memory
      implantation studies.
AB  - Understanding that suggestive practices can promote false beliefs and false
      memories for childhood events is important in many settings (e.g.,
      psychotherapeutic, medical, and legal). The generalisability of findings from
      memory implantation studies has been questioned due to variability in estimates
      across studies. Such variability is partly due to false memories having been
      operationalised differently across studies and to differences in memory induction
      techniques. We explored ways of defining false memory based on memory science and
      developed a reliable coding system that we applied to reports from eight
      published implantation studies (N = 423). Independent raters coded transcripts
      using seven criteria: accepting the suggestion, elaboration beyond the
      suggestion, imagery, coherence, emotion, memory statements, and not rejecting the
      suggestion. Using this scheme, 30.4% of cases were classified as false memories
      and another 23% were classified as having accepted the event to some degree. When
      the suggestion included self-relevant information, an imagination procedure, and
      was not accompanied by a photo depicting the event, the memory formation rate was
      46.1%. Our research demonstrates a useful procedure for systematically combining
      data that are not amenable to meta-analysis, and provides the most valid estimate
      of false memory formation and associated moderating factors within the
      implantation literature to date.

PMID- 27892835
TI  - Effect of Adhesive Restoration and Bleaching Technique on the Concentration of
      Hydrogen Peroxide In the Pulp Chamber.
AB  - This study aimed to quantify the concentration of hydrogen peroxide into the pulp
      chamber in the presence or absence of adhesive enamel restorations and to analyze
      the resin-dentin interface of bleached groups. Bovine incisors (120) were
      randomly divided into three groups according to enamel treatment (n=40 each): (1)
      enamel without restoration (control); (2) enamel cavities (3 mm diameter * 1.5 mm
      depth) restored with a silorane-based (SB) system; or (3) enamel cavities (3 mm
      diameter * 1.5 mm depth) restored with a dimethacrylate-based (DB) system.
      Restorations were thermocycled, and all groups were submitted to one application
      of 35% hydrogen peroxide (HP) agent for 45 minutes and subjected to four light
      activation methods (n=10 each): without light, light-emitting diode (LED),
      LED/diode laser, or halogen light. Acetate buffer solution was placed into the
      pulp chamber before bleaching, and this solution was collected to
      spectrophotometrically determine the concentration of HP that reached the pulp
      chamber after bleaching. Rhodamine B was added to the HP agent and applied on
      additional enamel samples of each group for 24 hours. Samples were sectioned
      mesiodistally, and the bleaching agent was traced using confocal microscopy.
      According to two-way analysis of variance and Tukey test (alpha=0.05), the HP
      concentration in the pulp chamber of the control group was significantly lower
      than that of the SB group (p<0.05), regardless of light activation. No
      differences were observed between DB and SB groups and between control and DB
      groups, except for the DB halogen light activated group, which exhibited higher
      HP intrapulpal concentration (p<0.05). Confocal microscopy exhibited HP diffusion
      through the interface of the SB and DB restored groups as well as enamel prisms
      in the control group. The SB restorative system increased the HP diffusion into
      the pulp chamber, but HP was able to diffuse even in the absence of enamel
      restorations.

PMID- 27892836
TI  - Comparison of Internal Adaptation in Class II Bulk-fill Composite Restorations
      Using Micro-CT.
AB  - PURPOSE: This study compared the internal adaptation of bulk-fill composite
      restorations in class II cavities and explored the relationship between internal
      adaptation and polymerization shrinkage or stress. METHODS AND MATERIALS:
      Standardized mesio-occluso-distal cavities were prepared in 40 extracted human
      third molars and randomly divided into five groups (n=8). After having been
      applied by total-etch XP bond (Dentsply Caulk, Milford, DE, USA) and light
      curing, the teeth were restored with the following resin composites: group 1,
      Filtek Z350 (3M ESPE, St. Paul, MN, USA); group 2, SDR (Dentsply Caulk, Milford,
      DE, USA) + Z350; group 3, Venus Bulk Fill (Heraeus Kulzer, Dormagen, Germany) +
      Z350; group 4, Tetric N-Ceram Bulk Fill (Ivoclar Vivadent, Schaan,
      Liechtenstein); and group 5, SonicFill (Kerr, West Collins, Orange, CA, USA).
      After thermo-mechanical load cycling, cross-sectional microcomputerized
      tomography (micro-CT) images were taken. Internal adaptation was measured as
      imperfect margin percentage (IM%), which was the percentage of defective margin
      length relative to whole margin length. On the micro-CT images, IM% was measured
      at five interfaces. Linear polymerization shrinkage (LS) and polymerization
      shrinkage stress (PS) were measured on each composite with a custom linometer and
      universal testing machine. To explore the correlation of IM% and LS or PS, the
      Pearson correlation test was used. RESULTS: The IM% of the gingival and pulpal
      cavity floors were inferior to those of the cavity walls. The IM% values of the
      groups were found to be as follows: group 5 <= groups 1 and 4 <= group 2 <= group
      3. The correlation analysis showed that the p value was 0.006 between LS and IM%
      and 0.003 between PS and IM%, indicating significant correlations (p<0.05).
      CONCLUSION: Flowable bulk-fill composites had a higher IM% and polymerization
      shrinkage stress than did packable bulk-fill and hybrid composites. In class II
      composite restoration, the gingival floor of the proximal box and pulpal floor of
      the cavity had higher IM% than did the buccal and lingual walls of the proximal
      box. LS and PS, which were measured under compliance-allowed conditions, were
      significantly related to internal adaptation.

PMID- 27892837
TI  - Conservative Anterior Partial Coverage CAD/CAM Restoration.
AB  - Computer-aided design and manufacturing technology enables practitioners to
      create, in a single appointment, indirect restorations that are esthetic and
      functionally unique to the patient's situation. The popular effort to perform
      minimally invasive dentistry using digital techniques with chairside milling can
      lead dentists to novel individualized restorative treatment. This article
      demonstrates a conservative anterior partial coverage restoration, utilizing both
      digital technology and chairside ceramic characterization to achieve an optimal
      esthetic outcome while preserving healthy tooth structure.

PMID- 27892838
TI  - Effect of Bioactive Primers on Bacterial-Induced Secondary Caries at the Tooth
      Resin Interface.
AB  - Secondary caries at the tooth-resin interface is the primary reason for
      replacement of resin composite restorations. The tooth-resin interface is formed
      by the interlocking of resin material with hydroxyapatite crystals in enamel and
      collagen mesh structure in dentin. Efforts to strengthen the tooth-resin
      interface have identified chemical agents with dentin collagen cross-linking
      potential and antimicrobial activities. The purpose of the present study was to
      assess protective effects of bioactive primer against secondary caries
      development around enamel and dentin margins of class V restorations, using an in
      vitro bacterial caries model. Class V composite restorations were prepared on 60
      bovine teeth (n=15) with pretreatment of the cavity walls with control buffer
      solution, an enriched fraction of grape seed extract (e-GSE), 1-ethyl-3-(3
      dimethyl aminopropyl)-carbodiimide/N-hydroxysuccinimide, or chlorhexidine
      digluconate. After incubating specimens in a bacterial model with Streptococcus
      mutans for four days, dentin and enamel were assessed by fluorescence microscopy.
      Results revealed that only the naturally occurring product, e-GSE, significantly
      inhibited the development of secondary caries immediately adjacent to the dentin
      resin interface, as indicated by the caries inhibition zone. No inhibitory
      effects were observed in enamel margins. The results suggest that the
      incorporation of e-GSE into components of the adhesive system may inhibit
      secondary caries and potentially contribute to the protection of highly
      vulnerable dentin-resin margins.

PMID- 27892839
TI  - Influence of Adhesive Type and Placement Technique on Postoperative Sensitivity
      in Posterior Composite Restorations.
AB  - PURPOSE: This double blind, randomized clinical trial compared the postoperative
      sensitivity of the placement technique (incremental and bulk fill) in posterior
      composite resin restorations bonded with two different adhesive strategies (self
      etch and etch-and-rinse). METHODS: Posterior dental cavities of 72 participants
      (n=236), with a cavity depth of at least 3 mm, were randomly divided into four
      groups. The restorations were bonded using either the etch-and-rinse Tetric N
      Bond (Ivoclar Vivadent) or the self-etch Tetric N-Bond SE (Ivoclar Vivadent). The
      composite resin Tetric N-Ceram Bulk Fill (Ivoclar Vivadent) was placed either
      incrementally or using the bulk-fill technique. Two experienced and calibrated
      examiners evaluated the restorations using World Dental Federation criteria after
      one week of clinical service. Spontaneous postoperative sensitivity was assessed
      using a 0-4 numerical rating scale and a 0-10 and 0-100 visual analog scale up to
      48 h after the restorative procedure and after one week. RESULTS: The risk
      (p>0.49) and intensity of spontaneous postoperative sensitivity (p>0.38) was not
      affected by the adhesive strategy or the filling technique. The overall risk of
      postoperative sensitivity was 20.3% (95% confidence interval 15.7-25.9) and
      typically occurred within 48 hours after the restorative procedure. CONCLUSIONS:
      The overall risk of immediate postoperative sensitivity was 20.3% and was not
      affected by either the adhesive strategy (etch-and-rinse/self-etch) or the
      filling technique (incremental/ bulk).

PMID- 27892840
TI  - Adhesive Cementation Promotes Higher Fatigue Resistance to Zirconia Crowns.
AB  - OBJECTIVE: The aim of this study was to investigate the influence of the
      cementation strategy on the fatigue resistance of zirconia crowns. The null
      hypothesis was that the cementation strategy would not affect the fatigue
      resistance of the crowns. METHODS AND MATERIALS: Seventy-five simplified molar
      tooth crown preparations were machined in glass fiber-filled epoxy resin.
      Zirconia crowns were designed (thickness=0.7 mm), milled by computer-aided
      design/computer-aided manufacturing, and sintered, as recommended. Crowns were
      cemented onto the resin preparations using five cementation strategies (n=15):
      ZP, luting with zinc phosphate cement; PN, luting with Panavia F resin cement;
      AL, air particle abrasion with alumina particles (125 MUm) as the crown inner
      surface pretreatment + Panavia F; CJ, tribochemical silica coating as crown inner
      surface pretreatment + Panavia F; and GL, application of a thin layer of
      porcelain glaze followed by etching with hydrofluoric acid and silanization as
      crown inner surface pretreatment + Panavia F. Resin cement was activated for 30
      seconds for each surface. Specimens were tested until fracture in a stepwise
      stress fatigue test (10,000 cycles in each step, 600 to 1400 N, frequency of 1.4
      Hz). The mode of failure was analyzed by stereomicroscopy and scanning electron
      microscopy. Data were analyzed by Kaplan-Meier and Mantel-Cox (log rank) tests
      and a pairwise comparison (p<0.05) and by Weibull analysis. RESULTS: The CJ group
      had the highest load mean value for failure (1200 N), followed by the PN (1026
      N), AL (1026 N), and GL (1013 N) groups, while the ZP group had the lowest mean
      value (706 N). Adhesively cemented groups (CJ, AL, PN, and GL) needed a higher
      number of cycles for failure than the group ZP did. The groups' Weibull moduli
      (CJ=5.9; AL=4.4; GL=3.9; PN=3.7; ZP=2.1) were different, considering the number
      of cycles for failure data. The predominant mode of failure was a fracture that
      initiated in the cement/zirconia layer. Finite element analysis showed the
      different stress distribution for the two models. CONCLUSION: Adhesive
      cementation of zirconia crowns improves fatigue resistance.

PMID- 27892841
TI  - Impact of the Swap It, Don't Stop It Australian National Mass Media Campaign on
      Promoting Small Changes to Lifestyle Behaviors.
AB  - Mass media campaigns aimed at influencing lifestyle risk factors are one way that
      governments are attempting to address chronic disease risk. In Australia, a
      national campaign aimed at encouraging Australians to make changes in lifestyle
      related behaviors was implemented from 2008 to 2011. The first phase, Measure Up
      (2008-2009), focused on why lifestyle changes are needed by increasing awareness
      of the link between waist circumference and chronic disease risk. The second
      phase, Swap It, Don't Stop It (2011), emphasized how adults can change their
      behaviors. Cross-sectional telephone surveys (after the campaign) were undertaken
      in July and November 2011 to evaluate the Swap It, Don't Stop It campaign and
      included measures of campaign awareness and lifestyle-related behavior change.
      Survey participants (N = 5,097) were similar across the two survey periods.
      Prompted campaign awareness was 62% (16% for unprompted awareness); females,
      younger respondents (18-44 years), those in paid employment, and those who spoke
      English at home were more likely to report prompted/unprompted campaign
      awareness. Moreover, 16% of survey respondents reported any swapping behavior in
      the previous 6 months, with the majority (14%) reporting only one swap; younger
      respondents and those in paid employment were significantly more likely to report
      having implemented a swapping behavior. The campaign achieved modest population
      awareness but demonstrated limited effect in terms of nudging behaviors. This
      evaluation indicates that encouraging swapping behaviors as a prelude to
      lifestyle change may not result from a mass media campaign alone; a comprehensive
      multicomponent population approach may be required.

PMID- 27892842
TI  - Complicated grief after suicide bereavement and other causes of death.
AB  - The authors compared baseline demographic characteristics, clinical features, and
      grief-related thoughts, feelings, and behaviors of individuals bereaved by
      suicide, accident/homicide and natural causes participating in a complicated
      grief (CG) treatment clinical trial. Severity of CG and depression and current
      depression diagnosis did not vary by loss type. After adjusting for baseline
      demographic features, time since death and relationship to the deceased, those
      with CG after suicide had the highest rates of lifetime depression, preloss
      passive suicidal ideation, self-blaming thoughts, and impaired work and social
      adjustment. Even among this treatment-seeking sample of research participants
      with CG, suicide survivors may face unique challenges.

PMID- 27892845
TI  - Learning Together 1: an educational model for training GPs, paediatricians:
      initial findings.
AB  - Learning Together is primarily an educational intervention, where paediatric
      registrars [SpRs] and General Practice (GP) registrars [GPSTs] see children
      together in a primary care setting. Over a six month period in 2013/2014, 44
      learning pairs were set up mainly in North East and Central London. Proof of
      concept for the model at scale was achieved. Reported learning demonstrated:
      clinical learning themes of new knowledge, skill and communication skills; and
      collaborative themes of ongoing collaboration, satisfaction with team working and
      change in attitudes. These themes were identified in both sets of trainees. The
      self-reported learning is backed up by the results of a retrospective notes
      review of four common conditions based on NICE guidelines; constipation, asthma,
      feverish illness and eczema (CAFE). Guidance adherence improved from 57% before
      the intervention in solo GP training consultations to 72% during the joint clinic
      intervention (p < 0.01). After the intervention when the GP registrars returned
      to normal consultations, guidance adherence was 77% compared to before the
      intervention (p < 0.01). In addition 99% of the parents, who handed in feedback
      forms or took part in interviews, reported a good experience of care, and 87%
      reported increased confidence to manage their children's health following the
      consultation. A second, linked article examines the cost utility of Learning
      Together in its South London extension.

PMID- 27892844
TI  - Identification of B-cell Epitope of Leishmania donovani and its application in
      diagnosis of visceral leishmaniasis.
AB  - Diagnosis of visceral leishmaniasis (VL) is often hindered by cross-reactions
      with antigens from other related parasite infections. This study aimed to develop
      an immunochromatographic test (ICT) which can detect the antigen present in
      circulating immune complexes (CICs) of VL patients using B-cell epitope-specific
      antibodies. MS analysis of six immunoreactive 2DE spots revealed two epitopes
      i.e. RFFVQGDGIGQHSLQEALERR (P1) and RRVAVLVLLDRL (P2) (From a hypothetical
      protein [Acc No: XP_003861458.1]). The epitope conservancy analysis suggested
      that the linear epitope (P1P2) is 97-100% conserved among Leishmania species and
      diverged from Homo sapiens (61% query coverage and 80% identity). Further,
      immunoinformatics analysis of hydrophilicity and flexibility confirmed the
      antigenicity of the peptide fragment. The linear epitope (P1P2) was synthesized
      (98% purity) and the purity was confirmed by high-performance liquid
      chromatography and MS. The indirect Enzyme linked immunosorbent assay results
      confirmed the presence of the corresponding antibody in VL patient's sera but not
      in those of healthy and other diseases. The result demonstrated a sensitivity
      90%; Se Cl95% (82.16-96.27)% and specificity 100%; Sp Cl95% (84.56-100)% which
      indicated the possibility to be used as a diagnostic tool. Sensitivity,
      specificity, and diagnostic efficiency of colloidal gold conjugated anti-P1P2
      antibody ICT strip was 100, 95.2, and 96.7%, respectively, which is slightly
      better as compared to other ICT for VL. Though, our result indicated the utility
      of anti-P1P2 antibody to detect CICs epitopes, a large-scale inspection in
      endemic and non-endemic area and in different ethnic population is needed for its
      validation and authentication.

PMID- 27892846
TI  - A Global Overview of Male Escort Websites.
AB  - This article details a preliminary dataset of global male escort sites to give
      insight into the scale of the online market. We conducted a content analysis of
      499 Web sites and also measured traffic to these sites. Our analysis examined the
      structural characteristics of escort services, geographical and regulatory
      contexts, and resilience of such services. Results suggest that most sites are
      independent and not affiliated to escort agencies, and the majority cater to male
      escorts soliciting male clients, with a number of sites for female clientele and
      couples. These Web sites are dispersed globally, with Asian, European, and South
      American countries the major hubs in the market and a small number of large
      multinational sites based in the United States and Europe figuring as a major
      presence in markets. Although still subject to high levels of regulation in many
      parts of the world, the data suggest that male escorting is becoming more visible
      in diverse cultural contexts as measured by the number of Web sites appearing in
      public spaces.

PMID- 27892847
TI  - International adoption from Ethiopia: An overview of the health status at arrival
      in Belgium.
AB  - BACKGROUND: Ethiopia is a densely populated country with a fast growing economy.
      Still socioeconomic and health issues render many children parentless. One
      thousand and twenty eight Ethiopian children have been adopted in Belgium from
      September 2005 to September 2015. Little has been published about their health
      status at arrival. METHODS: Three hundred and fifteen children adopted from
      Ethiopia were clinically evaluated at the Institute of Tropical Medicine in
      Antwerp from 1 January 2008 until 31 December 2014. Epidemiological and medical
      data were collected and analysed retrospectively. RESULTS: Data about 164 boys
      and 151 girls with a mean age of three years were analysed. Twenty per cent was
      adequately vaccinated, for 66.7% of children these data were absent. About 8.6%
      of the children were wasted/thin, 28.9% stunted. Skin abnormalities were seen in
      40.3%, especially Tinea capitis. No children tested positive for HIV, syphilis or
      hepatitis C. Four children had an acute or chronic hepatitis B (HBV) infection,
      eight children had a cured HBV infection. Two children tested positive for
      malaria. Active pulmonary tuberculosis was found in six children. Sixty-two per
      cent had one or more intestinal parasite. Giardia lamblia (41.9%) and
      Blastocystis hominis (27.0%) were most frequently isolated. There is a
      statistically relevant association between the number of intestinal parasites and
      age at presentation. In this group eosinophilia had a sensitivity of 30.2%, a
      specificity of 79.1% for intestinal parasites and a positive likelihood ratio of
      1.44 with a negative likelihood ratio of 0.88. CONCLUSION: Apart from the high
      prevalence of stunting and intestinal parasites important medical problems were
      infrequent. A systematic clinical examination and screening for infectious
      diseases remain important to ensure a healthy start of a new life in Belgium.

PMID- 27892848
TI  - Phytochemical screening and analgesic profile of the lyophilized aqueous extract
      obtained from Chrysobalanus icaco leaves in experimental protocols.
AB  - CONTEXT: Chrysobalanus icaco L. (Chrysobalanaceae) has been used for the
      treatment of abdominal pain and cramps. OBJECTIVE: Assess the chemical and
      pharmacological profile of the lyophilized aqueous extract from C. icaco leaves
      (AEC). MATERIALS AND METHODS: Chromatographic methods were used to assess
      compounds from AEC. Mice were treated with vehicle (control group) or AEC (100,
      200 or 400 mg/kg, p.o.) (group with 7-8 mice) and the analgesic profile was
      assessed employing the acetic acid-induced writhing, formalin, hot plate tests
      and hyperalgesia induced by carrageenan (CG) or tumour necrosis factor-alpha. The
      animal motor performance was assessed using rota-rod and grip strength tests.
      RESULTS: The chromatographic profile of AEC demonstrated the presence of
      terpenoid compounds. The acute pretreatment with AEC, at all doses, produced a
      significant (p < 0.01) inhibition of painful bahaviour (11.4 +/- 3.6; 10.3 +/-
      2.8; 11.3 +/- 2.2) when compared to the control group (24.7 +/- 4.7) in acetic
      acid-induced writhing test. In the formalin test, AEC were effective in the
      second phase (p < 0.01) (57.2 +/- 10.3; 56.3 +/- 9.2; 54.7 +/- 8.9) when compared
      to control group (121.9 +/- 18.5). No response was observed in the hot plate
      test. The higher dose of AEC produced a significant (p < 0.01 or p < 0.05)
      inhibitory effect on the mechanical hyperalgesia test. AEC did not affect the
      motor performance of the mice. DISCUSSION: The terpenoids from AEC are known for
      its analgesic and anti-inflammatory properties. So, these results corroborate the
      experiments using the AEC in inflammatory pain protocols. CONCLUSION: Our results
      suggest that AEC act against inflammatory pain.

PMID- 27892849
TI  - The impact of acute stress on cognitive functioning: a matter of cognitive
      demands?
AB  - INTRODUCTION: There is a controversy in the literature whether stress and related
      cortisol responses are beneficial or impairing for cognitive functioning.
      Conflicting results might be due to individual differences in stress reactivity
      and cognitive load of the applied tasks. METHODS: N = 48 participants underwent
      the Socially Evaluated Cold Pressor Test and were confronted with the Frankfurter
      Aufmerksamkeits-Inventar-2 (FAIR-2) which is a low-load attention task and two
      subscales of the Intelligenz-Struktur-Test 2000 R (I-S-T 2000R) as a high-load
      reasoning task before and after the stressor. Participants were post hoc divided
      into high (stress induced cortisol increase of >=1.5 nmol/l) vs. low-cortisol
      responders. RESULTS: Cortisol responders showed an increased attentional
      performance in the post-stress condition (eta2 > .14). However, there were
      neither stress or responder main effects nor an interaction effect on reasoning
      abilities. CONCLUSIONS: Results of the present study show that stress related
      changes in cognitive performance are due to individual differences in cortisol
      response and the cognitive load of the performed task. Future studies will show
      if these results are also valid for alternative cognitive tasks and if they can
      be replicated in female participants.

PMID- 27892850
TI  - Determination of 16 mycotoxins in vegetable oils using a QuEChERS method combined
      with high-performance liquid chromatography-tandem mass spectrometry.
AB  - A simple and efficient method for determining multiple mycotoxins was developed
      using a QuEChERS (quick, easy, cheap, effective, rugged and safe)-based
      extraction procedure in vegetable oils. High-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) was used for the quantification and
      confirmation of 16 chemically diversified mycotoxins. Different extraction
      procedures were studied and optimised by spiking 16 analytes into blank matrix,
      and the extraction with 85% MeCN solution and C18 as cleaning sorbent allowed an
      efficient recovery of 72.8-105.8% with RSDs less than 7%. The limit of detection
      (LOD) ranged from 0.04 to 2.9 ng g-1. The developed method was finally applied to
      screen mycotoxins in 62 vegetable oil samples. Zearalenone (ZEN), aflatoxin B1
      (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1) and alpha-zearalenol (alpha-ZOL)
      were detected, with maximum concentrations of 0.59 (AFG1)-42.5 (ZEN) ng g-1. The
      method developed has the advantages of high sensitivity, accuracy and
      selectivity, and it can be applied to the target screening of mycotoxins in real
      samples.

PMID- 27892851
TI  - Lovastatin fails to improve motor performance and survival in methyl-CpG-binding
      protein2-null mice.
AB  - Previous studies provided evidence for the alteration of brain cholesterol
      homeostasis in 129.Mecp2-null mice, an experimental model of Rett syndrome. The
      efficacy of statins in improving motor symptoms and prolonging survival of mutant
      mice suggested a potential role of statins in the therapy of Rett syndrome. In
      the present study, we show that Mecp2 deletion had no effect on brain and reduced
      serum cholesterol levels and lovastatin (1.5 mg/kg, twice weekly as in the
      previous study) had no effects on motor deficits and survival when Mecp2 deletion
      was expressed on a background strain (C57BL/6J; B6) differing from that used in
      the earlier study. These findings indicate that the effects of statins may be
      background specific and raise important issues to consider when contemplating
      clinical trials. The reduction of the brain cholesterol metabolite 24S
      hydroxycholesterol (24S-OHC) found in B6.Mecp2-null mice suggests the occurrence
      of changes in brain cholesterol metabolism and the potential utility of using
      plasma levels of 24S-OHC as a biomarker of brain cholesterol homeostasis in RTT.

PMID- 27892852
TI  - Physical basis of large microtubule aster growth.
AB  - Microtubule asters - radial arrays of microtubules organized by centrosomes -
      play a fundamental role in the spatial coordination of animal cells. The standard
      model of aster growth assumes a fixed number of microtubules originating from the
      centrosomes. However, aster morphology in this model does not scale with cell
      size, and we recently found evidence for non-centrosomal microtubule nucleation.
      Here, we combine autocatalytic nucleation and polymerization dynamics to develop
      a biophysical model of aster growth. Our model predicts that asters expand as
      traveling waves and recapitulates all major aspects of aster growth. With
      increasing nucleation rate, the model predicts an explosive transition from
      stationary to growing asters with a discontinuous jump of the aster velocity to a
      nonzero value. Experiments in frog egg extract confirm the main theoretical
      predictions. Our results suggest that asters observed in large fish and amphibian
      eggs are a meshwork of short, unstable microtubules maintained by autocatalytic
      nucleation and provide a paradigm for the assembly of robust and evolvable
      polymer networks.

PMID- 27892854
TI  - A comprehensive excitatory input map of the striatum reveals novel functional
      organization.
AB  - The striatum integrates excitatory inputs from the cortex and the thalamus to
      control diverse functions. Although the striatum is thought to consist of
      sensorimotor, associative and limbic domains, their precise demarcations and
      whether additional functional subdivisions exist remain unclear. How striatal
      inputs are differentially segregated into each domain is also poorly understood.
      This study presents a comprehensive map of the excitatory inputs to the mouse
      striatum. The input patterns reveal boundaries between the known striatal
      domains. The most posterior striatum likely represents the 4th functional
      subdivision, and the dorsomedial striatum integrates highly heterogeneous,
      multimodal inputs. The complete thalamo-cortico-striatal loop is also presented,
      which reveals that the thalamic subregions innervated by the basal ganglia
      preferentially interconnect with motor-related cortical areas. Optogenetic
      experiments show the subregion-specific heterogeneity in the synaptic properties
      of striatal inputs from both the cortex and the thalamus. This projectome will
      guide functional studies investigating diverse striatal functions.

PMID- 27892855
TI  - Application of ethnobotanical repellents and acaricides in prevention, control
      and management of livestock ticks: A review.
AB  - Ticks transmit at least the same number or even more pathogens than any other
      group of blood-feeding arthropods worldwide affecting humans and animals. The eco
      friendly control and management of tick vectors in a constantly changing
      environment is a crucial challenge. Besides the development of vaccines against
      ticks, IPM practices aimed at reducing tick interactions with livestock, emerging
      pheromone-based control tools, and few biological control agents, the extensive
      employment of acaricides and tick repellents still remain the most effective and
      ready-to-use strategies. However, the former is limited by the development of
      growing resistances as well as environmental concerns. Exploiting plants and
      plant products as sources of effective tick repellents and acaricides represents
      a promising strategy. In this scenario, the preservation of ethnobotanical
      information on repellent and acaricidal potential of plants is crucial. Here, we
      evaluated relevant information published in recent years, focused on plants used
      as repellents and acaricides against tick vectors in different regions worldwide.
      We selected a total of 238 plant species, which are traditionally used against
      ticks by native and local communities of Africa (Kenya, Uganda, Zimbabwe, South
      Africa), Europe (Serbia, Macedonia, Romania), Asia (Pakistan, India) and America
      (Brazil, Canada), from 56 families. However, only 7 families (i.e. Asteraceae,
      Euphorbiaceae, Fabaceae, Lamiaceae, Meliaceae, Apocynaceae and Solanaceae)
      represent the major quote (46%) of all plant species. We evaluated the
      differences in acaricidal and repellent efficacy of different formulations used.
      In the final section, implications arising from the surveyed anti-tick
      ethnobotanical knowledge and challenges for its future are discussed.

PMID- 27892856
TI  - Co-infection with Mycobacterium bovis does not alter the response to bovine
      leukemia virus in BoLA DRB3*0902, genetically resistant cattle.
AB  - High proviral load (HPL) profile in bovine leukemia virus infected animals poses
      increased risk of transmission, and development of HPL or low proviral load (LPL)
      profile may be attributed to host genetics. Genetic resistance and susceptibility
      has been mapped to the Major Histocompatibility Complex class II DRB3 gene (BoLA
      DRB3). The aim of this work was to determine the effect of Mycobacterium bovis
      infection on certain virological and host immunological parameters of BLV
      experimental infection. Twenty-six Argentinian Holstein calves carrying the
      resistance-associated marker allele BoLA DRB3*0902, susceptibility-associated
      marker allele BoLA DRB3*1501, or neutral BoLA DRB3 alleles, exposed to M. bovis
      were used. Twenty calves were inoculated with BLV, three were naturally infected
      and other three were BLV-negative. Seven from twenty six (27%) of the animals
      resulted positive to the PPD test. The proviral load, absolute leukocyte and
      lymphocyte counts, time to seroconversion, antibody titer against BLV, and viral
      antigen expression in vitro at various times post inoculation were determined and
      compared between PPD+ and PPD- animals. From a total of 23 BLV positive animals
      (naturally and experimentally infected), 13 (56.5%) developed HPL, and 10 (43.5%)
      developed LPL. None of the investigated parameters were affected by infection
      with M. bovis. We concluded that the ability of cattle carrying resistance
      associated marker to control BLV and to progress towards a LPL phenotype was not
      altered by M. bovis co-infection.

PMID- 27892857
TI  - Genotyping of German and Austrian Taylorella equigenitalis isolates using
      repetitive extragenic palindromic (REP) PCR and pulsed-field gel electrophoresis
      (PFGE).
AB  - A total of 124 Taylorella (T.) equigenitalis and five T. asinigenitalis field
      isolates collected between 2002 and 2014 were available for genotyping using REP-
      (repetitive extragenic palindromic) PCR and PFGE (pulsed-field gel
      electrophoresis). The study comprised 79 T. equigenitalis field isolates
      originating from ten defined breeds of German horses and revealed a spectrum of
      five REP (rep-E1-E4, rep-E3a) and 15 PFGE (TE-A1-A9, TE-B1-B3, TE-C, TE-E1, and
      TE-E2) genotypes. T. equigenitalis field isolates (n=40) obtained from Austrian
      Lipizzaner horses were differentiated into three REP (rep-E1, rep-E3a, and rep
      E4) and three PFGE genotypes (TE-A2, TE-A5, and TE-D); those isolated from four
      Austrian Trotters belonged to the REP/PFGE genotype rep-E2/TE-A1. Interestingly,
      a T. equigenitalis isolate recovered from a Holsteiner stallion living in South
      Africa revealed the REP/PFGE genotype rep-E1/TE-A5 which was otherwise
      exclusively present in the majority of Austrian Lipizzaner horses in our study.
      The type strain included in this study revealed the genotype REP/PFGE rep-E1/TE
      F. Six strains of T. asinigenitalis including the type strain were separated into
      three REP (rep-A1-A3) and six PFGE genotypes (TA-A1, TA-A2, TA-A3, TA-B, TA-C, TA
      D). Overall, the generated REP and PFGE genotypes showed a good correlation,
      whereas REP-PCR proved to be a suitable method for molecular epidemiological
      screening of T. equigenitalis and T. asinigenitalis isolates that should be
      differentiated in detail by genotyping using PFGE.

PMID- 27892858
TI  - Longitudinal study of CTX-M ESBL-producing E. coli strains on a UK dairy farm.
AB  - The aim of this study was to investigate the bacterial strains and farm
      environment that may contribute to the persistence of ESBL-producing E. coli on a
      single UK dairy farm. A longitudinal study was conducted comprising 6 visits,
      between August and October 2010, followed by a further visit at approximately
      69weeks after the initial visit. Faecal and environmental samples were collected
      from different parts of the farm. The persistence and extent of faecal shedding
      of ESBL E. coli by individual calves was also determined. Twenty two different
      PFGE types were identified. Four of these were persistent during the study period
      and were associated with serotypes: O98, O55, O141 and O33. The counts suggest
      that shedding in calf faeces was an important factor for the persistence of
      strains, and the data will be useful for parameterising mathematical models of
      the spread and persistence of ESBL strains within a dairy farm.

PMID- 27892859
TI  - The identification of potential behavioural indicators of pain in periparturient
      sows.
AB  - Periparturient pain is a welfare concern and could contribute to piglet losses.
      This has led to studies investigating post-farrowing analgesia. A clear reduction
      in pain has not been demonstrated, partly due to a lack of pain indicators. This
      study quantified behaviours as potential pain indicators (PPIn) in sows: i)
      before, during and after farrowing, and ii) 2min before and after piglet births.
      Twenty-five sows were observed during and after, and ten pre-farrowing. Behaviour
      recorded included: 1) back leg forward (back leg pulled forward and/or in); 2)
      tremble (movement as if shivering); 3) back arch (leg(s) stretch forming an
      arched back); 4) paw (leg scraped in pawing motion); and 5) tail flick (tail
      moved rapidly up and down). Behaviours were analysed using generalized linear
      models and Spearman's rank correlations. All PPIn were rare or absent pre
      farrowing, highest during farrowing, and back leg forward, tremble and back arch
      were greater in the early post-farrowing period. Several significant positive
      correlations between PPIn during and post-farrowing were found. Back arch, tail
      flick and paw were higher before than after a piglet birth, and were more
      frequent earlier in the birth order. Back leg forward and tremble did not differ
      before and after births, and tremble increased with birth order. These
      behaviours, which were absent or rare pre-farrowing, present during farrowing and
      were lower afterwards, and showed consistent individual variation, may be
      quantitatively associated with pain. Spontaneous behaviours could be used to test
      the efficacy of analgesics or identify sows that may benefit.

PMID- 27892853
TI  - Structure of the germline genome of Tetrahymena thermophila and relationship to
      the massively rearranged somatic genome.
AB  - The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes
      programmed chromosome breakage and massive DNA elimination to generate the
      somatic genome. Here, we present a complete sequence assembly of the germline
      genome and analyze multiple features of its structure and its relationship to the
      somatic genome, shedding light on the mechanisms of genome rearrangement as well
      as the evolutionary history of this remarkable germline/soma differentiation. Our
      results strengthen the notion that a complex, dynamic, and ongoing interplay
      between mobile DNA elements and the host genome have shaped Tetrahymena
      chromosome structure, locally and globally. Non-standard outcomes of
      rearrangement events, including the generation of short-lived somatic chromosomes
      and excision of DNA interrupting protein-coding regions, may represent novel
      forms of developmental gene regulation. We also compare Tetrahymena's
      germline/soma differentiation to that of other characterized ciliates,
      illustrating the wide diversity of adaptations that have occurred within this
      phylum.

PMID- 27892861
TI  - Effects of myxoma virus and rabbit hemorrhagic disease virus on the physiological
      condition of wild European rabbits: Is blood biochemistry a useful monitoring
      tool?
AB  - Myxomatosis and rabbit hemorrhagic disease (RHD) are the major viral diseases
      that affect the wild European rabbit (Oryctolagus cuniculus). These diseases
      arrived in Europe within the last decades and have caused wild rabbit populations
      to decline dramatically. Both viruses are currently considered to be endemic in
      the Iberian Peninsula; periodic outbreaks that strongly impact wild populations
      regularly occur. Myxoma virus (MV) and rabbit hemorrhagic disease virus (RHDV)
      alter the physiology of infected rabbits, resulting in physical deterioration.
      Consequently, the persistence and viability of natural populations are affected.
      The main goal of our study was to determine if blood biochemistry is correlated
      with serostatus in wild European rabbits. We carried out seven live-trapping
      sessions in three wild rabbit populations over a two-year period. Blood samples
      were collected to measure anti-MV and anti-RHDV antibody concentrations and to
      measure biochemical parameters related to organ function, protein metabolism, and
      nutritional status. Overall, we found no significant relationships between rabbit
      serostatus and biochemistry. Our main result was that rabbits that were
      seropositive for both MV and RHDV had low gamma glutamyltransferase
      concentrations. Given the robustness of our analyses, the lack of significant
      relationships may indicate that the biochemical parameters measured are poor
      proxies for serostatus. Another explanation is that wild rabbits might be
      producing attenuated physiological responses to these viruses because the latter
      are now enzootic in the study area.

PMID- 27892860
TI  - Microvascular lesions and changes in cell proliferation and death, and cytokine
      expression in the placentas of mice experimentally infected with Equid
      Herpesvirus 1.
AB  - This study describes the changes observed in the placentas of mice experimentally
      infected with an abortigenic strain of EHV-1 at mid-pregnancy and euthanized at
      days 3 and 4 post-infection. We analyzed microscopic vascular alterations, cell
      proliferation and death by immunohistochemistry, and the expression of IFN-gamma,
      TNF-alpha and the IL-10 by qPCR and flow cytometry. Infected mice showed slight
      respiratory signs and ruffled fur during the first two days post-infection. Virus
      isolation and DNA detection were positive only in the lungs of the infected mice.
      Vascular congestion, increase in the labyrinth area, and a significant reduction
      in fetal capillary endothelium surface of infected placentas were found. Cell
      proliferation was significantly reduced in the infected placentas, whereas the
      apoptosis was significantly increased. IL10, TNF and IFN-gamma showed different
      expression in the infected placentas and uteri. The effects of EHV-1 during
      pregnancy depend on different pathogenic mechanisms in which vascular
      alterations, and cell death and proliferation and local cytokine changes are
      compromised.

PMID- 27892862
TI  - Melamine negatively affects testosterone synthesis in mice.
AB  - Several studies have found that melamine causes damage to the testes, epididymis
      and sperm. However, few studies have investigated the effect of melamine on the
      synthesis of testosterone, which plays an import role in testicular development
      and spermatogenesis. In present study, mice were orally administrated with 2, 10
      or 50mg/kg of melamine for 28days. In these groups, various abnormalities were
      observed including disruption of the seminiferous tubule structure, an increased
      necrotic germ cells and sperm abnormalities, and a reduced sperm count. Melamine
      exposure also decreased the level of serum testosterone and levels of testicular
      StAR, P450scc and 17beta-HSD. In addition, melamine exposure reduced the number
      of Leydig cells. Taken together, these results indicate that melamine exposure
      reduces the level of testosterone through down-regulation of StAR and
      testosterone synthetic enzyme expression and also a decreased number of Leydig
      cells. This may further affect testicular development and lead to sperm damage.

PMID- 27892863
TI  - Nutrigenomic activity of plant derived compounds in health and disease: Results
      of a dietary intervention study in dog.
AB  - The study was conducted to investigate the effects of dietary administrations of
      four nutraceuticals in dogs. Seventy four dogs were enrolled in the trials, 24
      healthy dogs were fed with a control diet (CT) and the experimental groups
      received for 60days the same diet supplemented with nutraceuticals, namely
      Echinacea angustifolia (EA, 0.10mg/kg live weight as echinacoside; 14 dogs),
      Vaccinium myrtillus (VM, 0.20mg/kg live weight as anthocyanidin, 13 dogs),
      Curcuma longa (CL, 6.60mg/kg live weight as curcumin, 18 dogs with arthrosis),
      and Sylibum marianum (SM, 1.5mg/kg live weight as sylibin, 8 dogs with
      hepatopathy). Dogs were weighted at the beginning of study and blood samples were
      collected at the beginning (T0) and at the end (T60) of the study. VM
      significantly down regulated TNF, CXCL8, NFKB1 and PTGS2 and decreased plasma
      ceruloplasmin (CuCp). The activity of EA was evidenced by the significant
      decrease of TNF and NFKB1 expression and CuCp levels and by the increase of
      plasma Zn. Administration of CL caused a significant decrease of CuCp and
      increase of Zn and a down regulation of TNF, CXCL8, NFKB1 and PTGS2,
      corroborating the anti-inflammatory action of curcuminoids. After 60days of
      treatment with SM, plasma ALT/GPT activity was reduced and paraoxonase was
      increased, supporting the antioxidant activity of silymarin, also confirmed by
      the significant up regulation of SOD2. Results indicated that nutraceutical
      administrations in dogs can be an interesting approach to modulate immune
      response in order to improve health condition of animals.

PMID- 27892864
TI  - Influence of a low dosage of clopidogrel on platelet function in cats as measured
      by the platelet function analyser PFA-100 and the multiplate analyser.
AB  - The antiplatelet drug clopidogrel is widely used for prophylaxis of arterial
      thromboses in cats in a standard dosage of 18.75mg per cat once daily. The aim of
      the study was to verify if a reduced daily dose of 10mg clopidogrel per cat has a
      similar antiplatelet effect as the standard dosage. Platelet function was
      measured with the platelet function analyser PFA-100(r) and a novel impedance
      aggregometer. Suitability of the platelet function analyser was tested in
      citrated blood samples of 59 healthy cats and reference ranges were established.
      In addition, agonist concentrations for impedance aggregometry were optimised. In
      the main experiment two groups of 6 healthy cats received clopidogrel either in a
      dosage of 10 or 18.75mg per cat over a period of seven days. Analyses were
      performed on days 1, 2, 3, 5, and 7. In comparison to baseline both clopidogrel
      dosages showed an inhibitory effect on results of the platelet function analyser
      and velocity of ADP-induced platelet aggregation. Values at all times were
      different from baseline, with the exception of day 1 in cats receiving 10mg
      clopidogrel where the closure time of the platelet function analysis and part of
      ADP-induced aggregation did not show a significant difference. Significant
      differences were not found between the two doses. In conclusion, our study
      indicates that 10mg clopidogrel per day may be as effective as 18.75mg although
      the latter may be advantageous as an initial loading dosage to achieve effective
      levels more rapidly.

PMID- 27892865
TI  - Co-occurrence of a metastatic mammary liposarcoma and an ovarian sex-cord stromal
      tumor in a dog.
AB  - Sarcoma arising in the mammary gland is a rare tumor in dogs, and primary
      liposarcoma with metastatic behavior has never been previously reported among
      canine mammary tumors. A 14-year old female poodle had a mammary mass diagnosed
      as pleomorphic liposarcoma. Two years following surgical removal, the tumor
      recurred in the mammary gland with lymph node metastases. In addition, a sex-cord
      stromal tumor was identified in the ovary. Immunohistochemistry was performed on
      both tumors that were positive for oestrogen and progesterone receptors.
      Moreover, the ovarian tumor was positive for calretinin. This is the first report
      to the authors' knowledge, of the co-occurrence of a pleomorphic liposarcoma of
      the mammary gland and an ovarian sex-cord stromal (gonadostromal) tumor in the
      dog.

PMID- 27892866
TI  - Effectiveness of a BHV-1/BEFV bivalent vaccine against bovine herpesvirus type 1
      infection in cattle.
AB  - Bovine herpesvirus type 1 (BHV-1) causes acute febrile respiratory diseases
      (infectious bovine rhinotracheitis, IBR), decreased milk production, weight loss
      and abortion. Bovine ephemeral fever virus (BEFV) causes acute febrile
      respiratory disease, with pulmonary emphysema and pulmonary edema as the main
      signs. These viruses infect domesticated herds and lead to significant economic
      losses. In our previous study, an inactivated BHV-1 and BEFV bivalent vaccine was
      formulated with water-in-oil-in-water adjuvant, and vaccine efficacy was
      evaluated in guinea pigs. In this study, we evaluated the efficacy of the
      bivalent vaccine in cattle. Results showed that immunized cattle had a
      significantly higher level of total anti-BHV-1 antibody response (S/P ratio of
      12.7) than the control group (S/P ratio of 0.07) 32weeks post-vaccination. The
      immunized group also showed higher neutralizing antibody levels against BHV-1
      (SN=23.8) and BEFV (SN=24.6) than the control group (SN<2) 4 to 32weeks post
      vaccination (p<0.05). In a BHV-1 challenge experiment, immunized cattle showed
      low virus shedding (101.2TCID50/mL) and a significant reduction in pathological
      lesion scores (p<0.01). In conclusion, the BHV-1+BEFV+w/o/w vaccine not only
      improved long-term antibody immune response but also significantly reduced
      clinical signs in a BHV-1 challenge experiment. Our approach may be feasible for
      developing an effective vaccine against bovine herpesvirus type 1 and bovine
      ephemeral fever virus.

PMID- 27892867
TI  - The BALB/c mouse infection model for improving the Haemophilus parasuis
      serotyping scheme.
AB  - The use of BALB/c mouse as an alternative model to study Haemophilus parasuis
      (HPS) infections was evaluated, supplying the serotyping scheme by comparing the
      pathogenicity of different serovar HPS in pigs and mice challenge using
      statistical analysis. Results showed that the pathogenicity of different serovar
      HPS in mouse was consistent with in pigs, proving that this model is a viable
      alternative to pigs. It provides a convenient methodology for determining the
      virulence of HPS strains.

PMID- 27892869
TI  - Serum C-reactive protein and ferritin concentrations in dogs undergoing
      leishmaniosis treatment.
AB  - Monitoring of selected serum acute phase proteins like C-reactive protein (CRP)
      and ferritin could be useful for evaluation of the response to treatment in both
      naturally-occurring and experimentally-induced leishmaniosis. However studies
      until date have only been focused on dogs with an adequate response to the
      treatment and there is a lack of knowledge about the possible associations
      between the CRP and ferritin and the different clinicopathological conditions
      that can appear after treatment. Thus, the main objective of this retrospective
      study was to evaluate and compare the serum concentration of CRP and ferritin
      between three possible situations that dogs which undergo leishmaniosis treatment
      could have: responsive with total recovery, responsive with only clinical
      recovery but persistent abnormalities in biochemical analytes, and unresponsive
      with clinical and biochemical changes. All dogs which totally recovered after
      treatment showed CRP and ferritin values within reference ranges. Most of dogs
      classified as having only partial clinical remission had CRP and ferritin within
      the reference range values despite the presence of other biochemical
      abnormalities such as hyperglobulinemia, hyperproteinemia, or proteinuria. On the
      other hand, most of dogs in the unresponsive group had increased CRP and
      ferritin. Although the study has limitations due to the variability in the
      protocols and time periods of treatments, it can be concluded that CRP and
      ferritin concentrations within the reference ranges are usually associated with
      the absence of clinical signs and adequate response to treatment and increased
      CRP and/or ferritin values could reflect a lack of appropriate response to
      treatment.

PMID- 27892868
TI  - Risk assessment for changes in the metabolic profile and body weights of pre
      pubertal gilts during long-term monotonic exposure to low doses of zearalenone
      (ZEN).
AB  - The aim of the study was to examine whether the process of exposure to low doses
      of ZEN generates changes in the hematological and biochemical image of blood
      serum. During the experiment, pre-pubertal gilts (up to 25kg) were administered
      per os ZEN at a dose of 40MUg/kg BW (Group E, n=18) or placebo (Group C, n=21) on
      a daily basis for 42days. Blood samples for investigation were collected seven
      times at intervals of one week. In the experimental groups, slight but
      statistically significant changes in the values of selected biochemical blood
      indices such as glucose, ALT, Pin, total protein and Fe, or in hematological
      indices such as RBC, MCV, PLT, WBC, basophils, eosinophils and monocytes were
      observed. Based on statistical analysis between the groups, differences in the
      values of WBC, basophils, peroxidase negative cells, Hb, Ht, MCV, HDW, glucose,
      ALT, AP, total protein, iron or potassium were found. In Group E, decreasing
      trends in the values of PLT and glucose, and increasing trends in the values of
      total protein, Pin, Na and Cl were found. The described situations occurred
      during the last three weeks of exposure. Low levels of exposure to ZEN lead to
      completely different changes in the metabolic profile than those resulting from
      higher doses of the toxin. The stimulatory effect of mycotoxins, observed in
      initial stages of exposure, is eliminated when the compensatory response and
      adaptive mechanisms are triggered, and due to excessive loss of energy, which may
      point to more efficient feed utilization and/or detoxification processes. The
      values of body weight gain obtained in Group E were monotonically higher in four
      out of the six investigated weeks of exposure. The above changes were accompanied
      by a decrease in glucose concentrations and higher total protein levels (a rising
      tendency), which could have affected the rate of body weight gain.

PMID- 27892870
TI  - Nitric oxide modulates the immunological response of bovine PBMCs in an in vitro
      BRDc infection model.
AB  - Bovine respiratory disease complex (BRDc) is a multi-factorial disease, involving
      both viral and bacterial pathogens, that negatively impacts the cattle feedlot
      industry. A nitric oxide releasing solution (NORS) has been developed and shown
      to have potential in the prevention of BRDc. This study investigated the
      underlying immunological mechanisms through which the nitroslyating agent NORS
      provides protection against the development of BRDc in susceptible cattle. An in
      vitro BRDc experimental model was designed using bovine peripheral blood
      mononuclear cells (PBMCs) which were infected with bovine herpesvirus 1 (BHV-1)
      and subsequently cultured with lipopolysaccharides (LPS) extracted from
      Mannheimia haemolytica bacteria. The cells were treated with NORS following viral
      infection to reflect the timing of administering the NORS treatment in feedlots
      during initial processing. An expression and protein analysis of key genes
      involved in the innate immune response was carried out. The BRDc model produced
      significant increases in gene expression (p<0.01) and protein release (p<0.05) of
      the proinflammatory cytokines IL-1beta and TNF. Treatment with NORS reduced the
      protein levels of IL-1beta (0.39-fold?) (p<0.05) and TNF (0.48-fold?) (p<0.01) in
      the BRDc experimental group when compared against the non-treatment BRDc
      controls. TLR4 expression, having been significantly reduced under the BRDc
      experimental conditions (0.33-fold?) (p<0.05), increased significantly (0.76
      fold?) (p<0.05) following NORS treatment. This study provides evidence suggesting
      that NO may protect against the development of BRDc by limiting deleterious
      inflammation while simultaneously increasing TLR4 expression and enhancing the
      ability of the host to detect and respond to bacterial pathogens.

PMID- 27892872
TI  - Fern-synthesized silver nanocrystals: Towards a new class of mosquito oviposition
      deterrents?
AB  - Mosquitoes act as vectors of devastating pathogens and parasites, representing a
      key threat for millions of humans and animals worldwide. Eco-friendly control
      tools are urgently required. We proposed a novel method of fern-mediated
      biosynthesis of silver nanoparticles (AgNP) using Dicranopteris linearis, acting
      as a reducing and capping agent. AgNP were characterized by UV-vis spectroscopy,
      Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy
      (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), zeta
      potential and particle size analysis. In mosquitocidal assays, the LC50 of D.
      linearis extract against Aedes aegypti ranged from 165.213 (larva I) to
      255.055ppm (pupa). LC50 of D. linearis-synthesized AgNP ranged from 18.905 (larva
      I) to 29.328ppm (pupa). In the field, the application of D. linearis extract and
      AgNP (10*LC50) led to 100% larval reduction after 72h. Smoke toxicity experiments
      conducted against A. aegypti adults showed that D. linearis leaf-, stem- and root
      based coils evoked mortality rates comparable to the permethrin-based positive
      control (58%, 47%, 34%, and 48% respectively). In ovicidal experiments, egg
      hatchability was reduced by 100% after treatment with 25ppm of AgNP and 300ppm of
      D. linearis extract. Interestingly, oviposition deterrent assays highlighted that
      100ppm of fern extract reduced oviposition rates of more than 65%, while 10ppm of
      fern-fabricated AgNP reduced oviposition rates of more than 70% in A. aegypti
      (OAI were -0.52 and -0.55, respectively). Overall, our results highlighted that
      D. linearis-synthesized AgNP could be useful candidates to develop nano
      formulated oviposition deterrents effective against dengue vectors.

PMID- 27892871
TI  - Phenotypic modulation of porcine CD14+ monocytes, natural killer/natural killer T
      cells and CD8alphabeta+ T cell subsets by an antibody-derived killer peptide
      (KP).
AB  - An engineered killer peptide (KP) based on a recombinant anti-idiotypic antibody
      representing the functional image of a yeast killer toxin (KT) was demonstrated
      to mediate antimicrobial effects against fungi and viruses. KP binds to murine
      dendritic cells and macrophages and up-regulate co-receptor expression, thus
      sustaining CD4+ lymphocyte activation. No immunological data are available in
      domestic animals thus KP-induced immunomodulation was evaluated in porcine
      monocyte and lymphocyte subsets. PBMC from healthy adult pigs were stimulated
      with KP or a scramble peptide (SP), or kept unstimulated for 24, 48 and 72h, and
      subsequently analyzed by flow cytometry. In monocytes, KP induced a strong dose
      dependent shift from a major fraction of CD172alpha+CD14+low cells to a
      predominant fraction of CD172alpha+CD14+high cells, known to sustain leukocyte
      activation/differentiation and inflammatory responses. The CD16+ cell
      percentages, specifically the CD3+CD16+ natural killer T (NKT) cell fraction and
      CD16 expression showed an intense and stable dose-dependent increase while the
      CD3-CD16+ NK cell fraction decreased. CD4+ and CD8+ T cells increased and
      CD8alpha and CD8beta expression were up-regulated. CD8beta+ cytotoxic T cells and
      CD16+ cells comparably increased. A marked stimulation of activated CD16+CD25+
      and CD8beta+CD25+ cells was observed at 24h. The increase of CD8alpha+ cells and
      CD8alpha expression were due to increased CD4+CD8alpha+ (memory T helper) cells,
      also showing a CD8alpha+high phenotype. Concomitantly, the CD4+CD8alpha- T helper
      lymphocyte fraction significantly decreased. Overall, KP induced a wide
      modulation of innate immune and T cells that can exert regulatory and cytotoxic
      functions, which are fundamental for an efficient Th1 response.

PMID- 27892873
TI  - Evidence of disseminated infection by Mycobacterium avium subspecies hominissuis
      in a pet ferret (Mustela putorius furo).
AB  - The infection caused by the zoonotic opportunistic pathogen Mycobacterium avium
      subsp. hominissuis (Mah) was reported for the first time in a pet ferret. Both
      owners were HIV-positive. Euthanasia of the pet was recommended due to medical
      reasons and as a preventive action. Disseminated and open tuberculosis lesions
      were observed in the gastrointestinal and respiratory systems of the ferret.
      Ecographic and radiographic surveys showed a severe generalized lymphadenopathy,
      strong thickening of the gastric wall and peritoneum layer. The histopathological
      findings revealed a disseminated, granulomatous, chronic inflammation affecting
      the gastrointestinal tract, lungs, lymphoid tissues (spleen, tonsils and lymph
      nodes) and liver. Ziehl-Neelsen staining displayed the presence of positive acid
      fast bacilli within these granulomas. Bacteriology and sequencing of the isolates
      yielded Mah sequevar code 3. Ferrets can act as reservoirs of mycobacteria
      exposing their owners to the infection, which is of major concern in
      immunodeficient individuals, as those HIV-infected.

PMID- 27892874
TI  - Dynamics of the progesterone and cholesterol concentrations within the bovine
      corpus luteum cavity.
AB  - The aim of this study was to examine the concentrations of progesterone (P4) and
      cholesterol (CHOL) in fluid of cavitary corpus luteum (CL) and in serum of dairy
      cattle. Cavitary corpora lutea, collected from cows at a local abattoir, were
      divided in four stages of development, based on days of the estrous cycle (stage
      I: 1-4days; stage II: 5-10days; stage III: 11-17days; stage IV: 18-20). Fluid of
      the their cavity was aspirated and P4 and CHOL concentrations were evaluated. The
      concentrations of P4 in CL cavity fluids were very high (1640-4666.67ng/mL) and
      showed a peak at the stage III. CHOL values were similar to those of serum and
      the highest levels were found in the stage I.

PMID- 27892875
TI  - The zoonotic potential of Lactococcus garvieae: An overview on microbiology,
      epidemiology, virulence factors and relationship with its presence in foods.
AB  - Lactococcus garvieae is a relevant worldwide fish pathogen affecting various
      farmed and wild marine and freshwater species. It has also been isolated from
      other animals, such as ruminants with subclinical mastitis and pigs with
      pneumonia. From the early 90s, L. garvieae has been associated with different
      human infections, mainly endocarditis. During the last five years, human
      infections by this bacterium appear to be increasing, likely due to the
      improvement in microbiological methods for bacterial identification and the
      alertness of this bacterium by physicians. Human L. garvieae infections have been
      associated with the consumption or the handling of contaminated raw fish or
      seafood, and recently, a genetic study showed that meat, raw milk and dairy
      products may also be food sources of human L. garvieae infections. However, the
      status of L. garvieae as a potential zoonotic bacterium is still controversial to
      date. In this work, we describe four new human infections by L. garvieae in
      elderly and inmunocompromised patients, and we show an overview on L. garvieae
      microbiology, epidemiology, virulence factors and relationship with its presence
      in foods.

PMID- 27892876
TI  - Low expression of cyclooxygenase-2 in chronic kidney disease in young dogs.
AB  - Chronic kidney disease (CKD) often results in end-stage renal failure in young
      dogs; however, the pathogenesis of this disease is not established. This study
      investigated renal expression of cyclooxygenase (COX)-1 and COX-2 proteins in
      three dogs with chronic kidney disease by immunohistochemistry. Histopathology
      showed asynchronous differentiation of renal tissues, including immature
      glomeruli. COX-1 signals were not detected in diseased or normal kidneys. COX-2
      signals were low or undetectable in diseased kidneys, while normal kidneys showed
      clear positive signals in the macula densa (MD). Quantitative scores of COX-2 in
      diseased kidneys were significantly lower than those in normal kidneys. These
      findings demonstrate low renal COX-2 expression in CKD in young dogs, but whether
      this is correlated with disease pathogenesis remains unclear.

PMID- 27892877
TI  - Detection of porcine reproductive and respiratory syndrome virus (PRRSV) and
      influenza A virus (IAV) in oral fluid of pigs.
AB  - Recently oral fluid has become a novel sample type for pathogen nucleic acid and
      antibody detection, as it is easy to obtain with non-invasive procedures. The
      objective of the study was to analyze porcine reproductive and respiratory
      syndrome virus (PRRSV) and influenza A virus (IAV) circulation in growing pigs
      from three Polish production farms, using Real Time PCR and ELISA testing of oral
      fluid and serum. Oral fluids were collected every 2weeks, in the same 3-4 pens of
      pigs aged between 5 and 17weeks. Additionally, blood samples were collected every
      4weeks from 4 pigs corresponding to the same pens as oral fluid and tested for
      the presence of PRRSV nucleic acid (pooled by 4) and antibodies. In farm A no
      PRRSV circulation was detected and only maternal antibodies were present. In farm
      B and farm C antibodies to PRRSV in serum and oral fluid were detected in most
      samples. In farm B PRRSV Type 1 was detected in 80.9% of oral fluid samples and
      in 58.3% of serum pools, and in farm C in 92.8% of oral fluid samples and 75%
      serum pools. Striking differences were observed between different pens in PRRSV
      detection patterns. In farms B and C ORF5 sequence analysis showed the presence
      of wild type strains which were about 84-85% identical to the modified live
      vaccine used. In all three farms two waves of IAV shedding with oral fluid were
      detected, in weaners and fatteners.

PMID- 27892878
TI  - Inflammatory biomarkers are associated with ketosis in periparturient Holstein
      cows.
AB  - Ketosis is a prevalent periparturient metabolic disorder and we hypothesize that
      lipopolysaccharide (LPS) infiltration may play a key role in its etiology. Study
      objectives were to characterize biomarkers of inflammation during the transition
      period in healthy and clinically diagnosed ketotic cows. Cows were
      retrospectively categorized into one of two groups: healthy and clinically
      diagnosed ketotic. Two data sets were utilized; the first dataset (Study A) was
      obtained as a subset of cows (n=16) enrolled in a larger experiment conducted at
      the Iowa State University Dairy utilizing Holstein cows (8 healthy; 8 ketotic),
      and the second dataset (Study B; 22 healthy; 22 ketotic) was obtained from a
      commercial farm. For both experiments, blood samples were collected prior to and
      following calving. Ketotic cows in both studies had reduced milk production
      compared to healthy cows (P<0.01). Post-calving, ketotic cows had increased serum
      amyloid A (4.2 and 1.8 fold in studies A and B, respectively; P=0.03 and P=0.04),
      haptoglobin (>6 fold and ~4 fold; P=0.04 and P=0.03), and lipopolysaccharide
      binding protein (66 and 45%; P<0.01 and P=0.02) compared with their healthy
      counterparts. Antepartum circulating LPS in ketotic cows was increased (2.3 fold;
      P=0.01) compared to healthy cows in Study B. In summary, increased biomarkers of
      inflammation appear to be closely associated with ketosis in transition dairy
      cows.

PMID- 27892880
TI  - MRI cross sectional atlas of normal canine cervical musculoskeletal structure.
AB  - Although magnetic resonance imaging (MRI) has been increasingly used as a
      diagnostic tool for cervical spine injuries in canines, a comprehensive normal
      MRI anatomy of the canine cervical spine muscles is lacking. Therefore, the
      purpose of this study was to build a magnetic resonance imaging atlas of the
      normal cross sectional anatomy of the muscles of the canine cervical spine. MRI
      scans were performed on a canine cadaver using a combination of T1 and T2
      weighted images in the transverse, sagittal and dorsal planes acquired at a slice
      thickness of 1mm. Muscle contours were traced manually in each slice, using local
      osseous structures as reference points for muscle identification. Twenty-two
      muscles were traced in 401 slices in the cervical region. A three dimensional
      surface model of all the contoured muscles was created to illustrate the complex
      geometrical arrangement of canine neck muscles. The cross-sectional area of the
      muscles was measured at the mid-level of each vertebra. The accuracy of the
      location of the mapped muscles was verified by comparing the sagittal view of the
      3D model of muscles with still photographs obtained from anatomic canine cadaver
      dissection. We believe that this information will provide a unique and valuable
      resource for veterinary researchers, clinicians and surgeons who wish to evaluate
      MRI images of the cervical spine. It will also serve as the foundation for
      ongoing work to develop a computational model of the canine cervical spine in
      which anatomical information is combined with electromyographic, kinematic and
      kinetic data.

PMID- 27892879
TI  - Cytokine activation during embryonic development and in hen ovary and vagina
      during reproductive age and Salmonella infection.
AB  - Salmonellosis is one of the most important zoonotic diseases and is usually
      associated with consumption of Salmonella Enteritidis (SE) contaminated poultry
      meat or eggs. Contamination with SE is usually the result of infection of the
      digestive tract, or reproductive organs, especially the ovary and vagina. Thus,
      knowledge of endogenous innate immune mechanisms operating in the ovary and
      vagina of hen is an emerging aspect of reproductive physiology. Cytokines are key
      factors for triggering the immune response and inflammation in chicken to
      Salmonella infection. The aim of this study was to investigate the expression
      profile of 11 proinflammatory cytokines in the chicken embryos during embryonic
      development, as well as in the hen ovary and vagina in vivo, to investigate
      whether sexual maturation affects their ovarian and vaginal mRNA abundance and to
      determine whether cytokine expression was constitutive or induced in the ovary
      and vagina as a response to SE infection. RT-PCR analysis revealed that several
      cytokines were expressed in the chicken embryos, and in the ovary and vagina of
      healthy birds. Expression of various cytokines during sexual maturation appeared
      to be developmentally regulated. In addition, a significant up-regulation of
      several cytokines in the ovary and vagina of sexually mature SE infected birds
      compared to healthy birds of the same age was observed. These results suggest a
      cytokine-mediated immune response mechanism against Salmonella infection in the
      hen reproductive organs.

PMID- 27892881
TI  - Comparison of visual assessment of coronary stenosis with independent
      quantitative coronary angiography: Findings from the Prospective Multicenter
      Imaging Study for Evaluation of Chest Pain (PROMISE) trial.
AB  - BACKGROUND: The outcomes in patients by visual assessment and quantitative
      coronary angiography (QCA) for obstructive coronary artery disease (CAD) are not
      known. Our objectives were to compare visual and QCA estimates of obstructive CAD
      and to assess their relationship to outcomes in stable patients with symptoms of
      CAD. METHODS: The PROMISE trial randomized 10,003 patients with CAD symptoms to
      anatomical or functional testing. Site reports of invasive angiography detailing
      visual stenosis and independent, blinded QCA were performed for obstructive CAD
      (>=50% stenosis). Disagreement between methods was determined and compared with
      outcomes (death, myocardial infarction, unstable angina hospitalization, or major
      procedural complications). RESULTS: Of 929 patients (9.3% of PROMISE cohort) with
      angiograms assessed by sites and QCA, 593 (64%) had obstructive CAD per site
      reports, whereas 428 (46%) had stenosis >=50% per QCA. Results differed in 177
      patients (disagreement rate 19.1%, kappa=0.63), of whom 171 had CAD per sites but
      not per QCA. One-year unadjusted Kaplan-Meier event rates were highest (5.1%)
      when QCA and visual assessment agreed for CAD, lowest (0.9%) when the 2 agreed
      for no obstructive CAD, and intermediate (3.1%) for patients who had CAD per
      visual assessment but not per QCA. CONCLUSIONS: Visual estimation of angiograms
      results in more frequent diagnosis of obstructive CAD as compared with QCA.
      Concordance of results for presence or absence of obstructive CAD was associated
      with high and low event rates, respectively. Disagreement was associated with
      intermediate event rates, suggesting that cardiologists integrated clinical
      information into routine visual assessment of angiograms.

PMID- 27892882
TI  - Clinical and angiographic predictors of persistently ischemic fractional flow
      reserve after percutaneous revascularization.
AB  - AIMS: Despite optimal angiographic results after percutaneous coronary
      intervention (PCI), some lesions may continue to produce ischemia under maximal
      hyperemia. We evaluated the factors associated with persistently ischemic
      fractional flow reserve (FFR) after angiographically successful PCI. METHODS AND
      RESULTS: A total of 574 consecutive patients with 664 lesions undergoing PCI who
      had FFR pre- and post-PCI were analyzed. Percutaneous coronary intervention led
      to effective ischemia reduction from pre-FFR (0.65+/-0.14) to post-FFR (0.87+/
      0.08; ?FFR 0.22+/-0.16, P<.001). There were 63 (9.5%) lesions with a persistently
      ischemic FFR of <=0.80 despite optimal angiographic PCI results. Multivariate
      analysis revealed the presence of diffuse disease (odds ratio [OR] 3.54, 95% CI
      1.80-6.94, P<.01), left anterior descending artery PCI (OR 8.35, 95% CI 3.82
      18.27, P<.01), use of intravenous adenosine for inducing hyperemia (OR 3.95, 95%
      CI 2.0-7.84, P<.01), and pre-PCI FFR (OR 0.03, 95% CI 0.004-0.23, P<.01) as
      independent predictors of persistently ischemic FFR (<=0.80) after PCI. The
      predictive accuracy of this model was robust, with an area under the curve of
      0.85 (95% CI 0.82-0.88). CONCLUSION: Multiple factors are associated with
      persistently ischemic FFR after angiographically optimal PCI. It is recommended
      that in lesions with the above-identified factors, FFR should be remeasured after
      PCI, and if abnormal, further measures should be undertaken for functional
      optimization.

PMID- 27892883
TI  - Predicting long-term prognosis in stable peripheral artery disease with baseline
      functional capacity estimated by the Duke Activity Status Index.
AB  - BACKGROUND: The ability of a simple self-assessment tool for estimated functional
      capacity to predict long-term prognosis in patients with established peripheral
      artery disease (PAD) is unknown. We investigate whether subjective measurement of
      functional capacity estimated by using the Duke Activity Status Index (DASI)
      questionnaire predicts long-term prognosis in patients with established PAD.
      METHODS: We administered the DASI questionnaire to 771 stable patients with
      established PAD who underwent elective diagnostic coronary angiography with 5
      year follow-up all-cause mortality. RESULTS: Two hundred ten patients (27%) died
      over a 5-year follow-up. The lowest DASI score was associated with a 3.2-fold
      increased risk of 5-year all-cause mortality (unadjusted hazard ratio 3.23, 95%
      CI 2.19-4.75, P<.001). After adjustments for traditional risk factors, estimated
      glomerular filtration rate, high-sensitivity C-reactive protein, and lowest DASI
      score remained predictive of 5-year all-cause mortality (adjusted hazard ratio
      2.09, 95% CI 1.36-3.23, P<.001). Interestingly, the lowest DASI score remained to
      predict 5-year all-cause mortality regardless of each PAD diagnosis subtype
      (including lower extremity, non-lower extremity, or carotid artery PAD), although
      the mortality risk was attenuated when incorporating heart disease severity in
      the non-lower extremity group. CONCLUSIONS: A simple self-assessment tool of
      functional capacity provides an independent and incremental prognosis value for
      long-term adverse clinical events in stable patients with established PAD beyond
      each PAD diagnostic subtype.

PMID- 27892884
TI  - beta-blocker dosage and outcomes after acute coronary syndrome.
AB  - BACKGROUND: Although beta-blockers increase survival in acute coronary syndrome
      (ACS) patients, the doses used in trials were higher than doses used in practice,
      and recent data do not support an advantage of higher doses. We hypothesized that
      rates of major adverse cardiac events (MACE), all-cause death, myocardial
      infarction, and stroke are equivalent for patients on low-dose and high-dose beta
      blocker. METHODS: Patients admitted to Intermountain Healthcare with ACS and
      diagnosed with >=70% coronary stenosis between 1994 and 2013 were studied (N =
      7,834). We classified low dose as <=25% and high dose as >=50% of an equivalent
      daily dose of 200 mg of metoprolol. Multivariate analyses were used to test
      association between low-dose versus high-dose beta-blocker dosage and MACE at 0-6
      months and 6-24 months. RESULTS: A total of 5,287 ACS subjects were discharged on
      beta-blockers (87% low dose, 12% high dose, and 1% intermediate dose). The 6
      month MACE outcomes rates for the beta-blocker dosage (low versus high) were not
      equivalent (P = .18) (hazard ratio [HR] = 0.76; 95% CI, 0.52-1.10). However,
      subjects on low-dose beta-blocker therapy did have a significantly decreased risk
      of myocardial infarction for 0-6 months (HR = 0.53; 95% CI, 0.33-0.86). The rates
      of MACE events during the 6-24 months after presentation with ACS were equivalent
      for the 2 doses (P = .009; HR = 1.03 [95% CI, 0.70-1.50]). CONCLUSIONS: In ACS
      patients, rates of MACE for high-dose and low-dose beta-blocker doses are
      similar. These findings question the importance of achieving a high dose of beta
      blocker in ACS patients and highlight the need for further investigation of this
      clinical question.

PMID- 27892885
TI  - Vitamin K antagonists for stroke prevention in hemodialysis patients with atrial
      fibrillation: A systematic review and meta-analysis.
AB  - BACKGROUND: The use of vitamin K antagonists (VKAs) in hemodialysis patients with
      atrial fibrillation (AF) is controversial. No randomized trials are available and
      observational studies have yielded conflicting results, engendering a large
      clinical practice variability and physician uncertainty. An unresolved but highly
      relevant question is whether AF poses a true risk of ischemic stroke in
      hemodialysis and whether any form of oral anticoagulation is therefore warranted.
      METHODS: We conducted a systematic review of studies that compared the incidence
      of ischemic stroke and bleeding in hemodialysis patients with AF taking VKA and
      those not taking VKA. When hemodialysis patients had been pooled with peritoneal
      dialysis, kidney transplant, or stage V chronic kidney disease patients,
      unpublished outcome data of the hemodialysis subgroup were obtained through
      personal communication. The main outcome measures were ischemic
      stroke/thromboembolic events, all-cause mortality, major bleeding, and
      hemorrhagic stroke. Combined hazard ratios (HRs) and 95% CIs were calculated
      using a random-effects model. RESULTS: Twelve prospective or retrospective cohort
      studies were included in the meta-analysis, totaling 17,380 hemodialysis patients
      of whom 4,010 (23.1%) received VKA. In VKA-treated patients, mean CHADS2 or
      CHA2DS2VASc score was low (range 1.7-2.75) or a sizeable proportion of patients
      had scores <2 (range 2%-23%). Time in the therapeutic range or mean international
      normalized ratio was generally low. Treatment with VKA was associated with a
      nonsignificant 26% reduction of the risk of ischemic stroke (HR 0.74; 0.51-1.06),
      a 21% increase in total bleeding risk (HR 1.21; 1.03-1.43), and no effect on
      mortality (HR 1.00; 0.92-1.09). Vitamin K antagonist almost doubled the risk of
      hemorrhagic stroke, but this did not reach the limit of statistical significance
      (4 studies, n = 16.365; HR 1.93; 0.93-3.98). CONCLUSION: Our meta-analysis
      revealed a trend for a reduction of the risk of ischemic stroke in hemodialysis
      patients with AF treated with VKA. The true protective effect may have been
      underestimated, owing to inclusion of low-risk patients not expected to benefit
      from anticoagulation and to suboptimal anticoagulation. However, assessment of
      the overall effect of VKA in hemodialysis patients should also take into account
      the increased risk of bleeding, in particular of hemorrhagic stroke. Whether new
      oral anticoagulants provide a better benefit-risk ratio in hemodialysis patients
      should be the subject of future trials.

PMID- 27892887
TI  - Cardiorespiratory fitness and nonfatalcardiovascular events: A population-based
      follow-up study.
AB  - BACKGROUND: To examine the prognostic value of cardiorespiratory fitness (CRF)
      with risk of first major nonfatal myocardial infarction (MI), stroke, and heart
      failure (HF) events. METHODS: Cardiorespiratory fitness, as measured by maximal
      oxygen uptake, was assessed at baseline in a prospective cohort of 2,089 men aged
      42 to 61years. RESULTS: During a mean (SD) follow-up of 19.1(8.4) years, 522
      nonfatal acute MI events, 198 acute all-cause nonfatal stroke events, and 221
      nonfatal HF events were recorded. The hazard ratio per 1-metabolic-equivalent
      increase in CRF was 0.93 (95% CI 0.88-0.97) for nonfatal MI, 0.94 (95% CI0.87
      1.01) for nonfatal stroke, and 0.84 (95% CI 0.78-0.91) for nonfatal HF events
      after adjustment for cardiovascular risk factors (age, systolic blood pressure,
      body mass index, history of cardiovascular disease, diabetes, smoking, alcohol
      use, serum creatinine, low-density lipoprotein levels, physical activity, and
      socioeconomic status). Further adjustment for left ventricular hypertrophy and
      resting heart rate did not attenuate these associations. Addition of CRF to
      conventional cardiovascular disease risk factors significantly improved both
      discrimination (C index) and category free net reclassification index (cf-NRI)
      for nonfatal MI (change in C index, 0.015 [95% CI 0.010-0.020] and change in cf
      NRI 0.27, P<.01) and HF (change in C index 0.040 [95% CI 0.010-0.060] and change
      in cf-NRI 0.88, P<.01). CONCLUSION: In this Finnish population, there is a
      strong, inverse, and independent association between CRF and acute nonfatal MI
      and HF risk.

PMID- 27892886
TI  - Safety profile and utility of treadmill exercise in patients with high-gradient
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Exercise echocardiography in the evaluation of hypertrophic
      cardiomyopathy (HCM) provides valuable information for risk stratification,
      selection of optimal treatment, and prognostication. However, HCM patients with
      left ventricular outflow tract gradients >=30mm Hg are often excluded from
      exercise testing because of safety considerations. We examined the safety and
      utility of exercise testing in patients with high-gradient HCM. METHODS: We
      evaluated clinical characteristics, hemodynamics, and imaging variables in 499
      consecutive patients with HCM who performed 959 exercise tests. Patients were
      divided based on peak left ventricular outflow tract gradients using a 30-mm Hg
      threshold into the following: obstructive (n=152), labile-obstructive (n=178),
      and nonobstructive (n=169) groups. RESULTS: There were no deaths during exercise
      testing. We noted 20 complications (2.1% of tests) including 3 serious
      ventricular arrhythmias (0.3% of tests). There was no difference in complication
      rate between groups. Patients with obstructive HCM had a higher frequency of
      abnormal blood pressure response (obstructive: 53% vs labile: obstructive: 41%
      and nonobstructive: 37%; P=.008). Obstructive patients also displayed a lower
      work capacity (obstructive: 8.4+/-3.4 vs labile obstructive: 10.9+/-4.2 and
      nonobstructive: 10.2+/-4.0, metabolic equivalent; P<.001). Exercise testing
      provided incremental information regarding sudden cardiac death risk in 19% of
      patients with high-gradient HCM, and we found a poor correlation between patient
      reported functional class and work capacity. CONCLUSION: Our results suggest that
      exercise testing in HCM is safe, and serious adverse events are rare. Although
      numbers are limited, exercise testing in high-gradient HCM appears to confer no
      significant additional safety hazard in our selected cohort and could potentially
      provide valuable information.

PMID- 27892888
TI  - Early, de novo atrial fibrillation after coronary artery bypass grafting: Facts
      and features.
AB  - : Knowledge of the mechanism underlying post-operative atrial fibrillation (PoAF)
      is essential for development of preventive measures. The incidence and
      characteristics of both PoAF and supraventricular premature beats triggering
      PoAF, their interrelationship and alterations over time have never been examined.
      The goal of this study is therefore to examine the correlation between the
      incidence and characteristics of supraventricular premature beats (SVPBs) and
      PoAF episodes in patients undergoing CABG in the first five post-operative days.
      METHODS: PoAF episodes (N=327) and SVPBs (N=141,873) were characterized in 29
      patients (63+/-9 years; 22 (76%) male) undergoing coronary artery bypass grafting
      and compared with a control group of patients without PoAF by using continuous
      cardiac rhythm monitoring during the first 5 days after surgery. RESULTS: Most
      patients (N=18, 62%) had multiple PoAF episodes; the median number of PoAF
      episodes per patient was 3 and varied between 1 and 139. The majority of PoAF
      episodes developed on the second and third post-operative day (55%). The averaged
      median duration of PoAF episodes per patient was 469+/-1085 min. Patients with
      PoAF had a higher SVPBs burden compared to subjects without PoAF (0.9% vs 0.2%,
      P<.001). SVPBs initiating PoAF had shorter coupling intervals than SVPBs which
      did not initiate PoAF episodes (58% vs 64% (P<.001) and were preceded by heart
      rate acceleration. CONCLUSION: PoAF episodes are mainly repetitive though
      transient in nature. There was a considerable inter-individual variation in both
      AF and SVPB characteristics, despite a similar underlying clinical profile. The
      SVPB burden is higher in patients with PoAF and the mode of onset is
      characterized by short coupled SVPBs. Determination of individual post-operative
      dysrhythmia profiles enables identification of patients at risk for developing
      PoAF.

PMID- 27892889
TI  - The impact of functional vs degenerative mitral regurgitation on clinical
      outcomes among patients undergoing transcatheter aortic valve implantation.
AB  - BACKGROUND: Among patients undergoing transcatheter aortic valve implantation
      (TAVI), concomitant mitral regurgitation (MR) has been associated with adverse
      prognosis. We aimed to assess long-term clinical outcomes according to MR
      etiology. METHODS: In a single-center registry of consecutive patients undergoing
      TAVI, we investigated the impact of functional (FMR) vs degenerative (DMR) MR on
      cardiovascular (CV) mortality throughout 2years of follow-up. RESULTS: Among 603
      patients (mean age 82.4+/-5.7years, 55% female) undergoing TAVI, 149 patients had
      moderate or severe MR (24.7%). Functional MR and DMR were documented in 53 (36%)
      and 96 (64%) patients, respectively. At 2years, patients with FMR and DMR had
      higher rates of CV mortality (30.2% vs 32.4%) as compared with patients with no
      MR (14.6%; FMR vs no MR: hazard ratio [HR] 2.32, 95% CI 1.34-4.02, P=.003; DMR vs
      no MR: HR 2.56, 95% CI 1.66-3.96, P<.001). In adjusted analyses, DMR was
      associated with an increased risk of CV mortality throughout the 2-year follow-up
      (adjusted HR 2.21, 95% CI 1.4-3.49, P=.001) as compared with FMR (adjusted HR
      1.13, 95% CI 0.59-2.18, P=.707). Relevant MR was postprocedurally significantly
      reduced in both the DMR and FMR groups, whereas improvement of a decreased left
      ventricular ejection fraction was predominantly seen in the FMR group as compared
      with baseline. CONCLUSION: Patients with severe, symptomatic aortic stenosis
      undergoing TAVI complicated by moderate or severe MR portend impaired prognosis.
      Particularly, patients with DMR are at increased risk for CV mortality during
      long-term follow-up.

PMID- 27892890
TI  - Trial design: Rivaroxaban for the prevention of major cardiovascular events after
      transcatheter aortic valve replacement: Rationale and design of the GALILEO
      study.
AB  - BACKGROUND: Optimal antithrombotic treatment after transcatheter aortic valve
      replacement (TAVR) is unknown and determined empirically. The direct factor Xa
      inhibitor rivaroxaban may potentially reduce TAVR-related thrombotic
      complications and premature valve failure. DESIGN: GALILEO is an international,
      randomized, open-label, event-driven, phase III trial in more than 1,520 patients
      without an indication for oral anticoagulation who underwent a successful TAVR
      (ClinicalTrials.govNCT02556203). Patients are randomized (1:1 ratio), 1 to 7days
      after a successful TAVR, to either a rivaroxaban-based strategy or an
      antiplatelet-based strategy. In the experimental arm, subjects receive
      rivaroxaban (10mg once daily [OD]) plus acetylsalicylic acid (ASA, 75-100mg OD)
      for 90days followed by rivaroxaban alone. In the control arm, subjects receive
      clopidogrel (75mg OD) plus ASA (as above) for 90days followed by ASA alone. In
      case new-onset atrial fibrillation occurs after randomization, full oral
      anticoagulation will be implemented with maintenance of the original treatment
      assignment. The primary efficacy end point is the composite of all-cause death,
      stroke, myocardial infarction, symptomatic valve thrombosis, pulmonary embolism,
      deep venous thrombosis, and systemic embolism. The primary safety end point is
      the composite of life-threatening, disabling, and major bleeding, according to
      the Valve Academic Research Consortium definitions. CONCLUSIONS: GALILEO will
      test the hypothesis that a rivaroxaban-based antithrombotic strategy reduces the
      risk of thromboembolic complications post-TAVR with an acceptable risk of
      bleeding compared with the currently recommended antiplatelet therapy-based
      strategy in subjects without need of chronic oral anticoagulation.

PMID- 27892892
TI  - Impact of lymphocyte culture media on the number of metaphases and chromosome
      band resolution.
AB  - A special type of differential staining of chromosomes is replication banding.
      This staining technique reveals the band pattern characteristic of each
      homologous pair of chromosomes, which is a reflection of heterogeneous
      euchromatin structure. Banding enables identification of homologous chromosomes
      and detection of chromosomal aberrations, both structural and numerical. Slide
      preparation requires knowledge of many techniques, and the procedure is often
      different for each laboratory. The aim of the study was to determine the effect
      of selected media for lymphocyte cultures on the number of metaphases and the
      band resolution of chromosomes. The study was carried out using cell cultures
      from whole peripheral blood. The slides were stained by the GTG method. After
      their removal from the water bath they were immersed in trypsin solution, then
      rinsed in PBS solution and stained in Giemsa solution. After staining they were
      rinsed again and left to dry. The study confirmed the effect of selected
      commercially available cell media on the number of metaphases and band resolution
      of chromosomes, which have not previously been described. In all of the tests
      performed, the cell culture, fixation, slide preparation (automatic method),
      staining, and number of reagents were identical.

PMID- 27892894
TI  - Overuse of proton pump inhibitors and its consequences.
AB  - Direct inhibition of H+ ion excretion to the gastric lumen makes proton pump
      inhibitors (PPI) the most effective drugs against gastric acid-related diseases.
      Over recent years usage of proton pump inhibitors has increased dramatically. Due
      to the low costs, high efficacy and rarity of adverse effects, their use is
      prevalent and often it does not correspond with existing medical guidelines. The
      literature lists stress ulcer prophylaxis among patients with low risk of
      bleeding, routine 'gastroprotective' medication during treatment and non-specific
      abdominal symptoms as the most common patterns of off-label PPI use. This article
      summarizes the influence of PPI therapy on gastric mucosa, absorption and
      occurrence of adverse effects. The authors note that their low awareness among
      physicians contributes to wide and imprudent use of drugs of this group.

PMID- 27892893
TI  - Photoprotective and radioprotective properties of nitroxides and their
      application in magnetic resonance imaging.
AB  - Nitroxides are a group of stable organic radicals of low molecular weight having
      a nitroxyl group > N-.O, which has an unpaired electron. The presence of this
      group allows a nitroxide to participate in redox reactions. They serve as mimics
      of superoxide dismutase (SOD) and have stimulative properties towards
      haemoproteins with catalase-like activity. Nitroxides oxidize Fe (II) to Fe (III)
      preventing the Fenton and Haber-Weiss reactions. As the radicals have the ability
      to scavenge other free radicals. Nitroxides are not immunogenic, and mutagenic
      and do not show toxicity to the human cells. The review discusses the use of
      nitroxide in protecting cells and tissues from the effects of UVA radiation.
      Preliminary studies indicate that they are more effective than conventionally
      used vitamins C and E and UV filters. They also protect the biological material
      from the effects of ionizing radiation. Nitroxides protect healthy cells and
      simultaneously they do not protect cancer cells from ionizing radiation. The
      differences in the nitroxide activity are associated with conditions prevailing
      in the oxidizing environment of the tumor as opposed to reducing conditions in
      normal cells. Nitroxides can be used as contrast agents in the magnetic resonance
      imaging (MR). They have ability of detection of subtle changes in redox
      equilibrium in the tumor tissue. Application of nitroxides in MR method allow to
      distinguish normal and pathological state of tissue. Successful investigations
      using this technique were conducted in mice with colon and brain cancer.

PMID- 27892891
TI  - Atorvastatin for high-risk statin-naive patients undergoing noncardiac surgery:
      The Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose
      (LOAD) randomized trial.
AB  - : Preliminary evidence suggests that statins may prevent major perioperative
      vascular complications. METHODS: We randomized 648 statin-naive patients who were
      scheduled for noncardiac surgery and were at risk for a major vascular
      complication. Patients were randomized to a loading dose of atorvastatin or
      placebo (80 mg anytime within 18hours before surgery), followed by a maintenance
      dose of 40 mg (or placebo), started at least 12hours after the surgery, and then
      40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause
      mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at
      30days. RESULTS: The primary outcome was observed in 54 (16.6%) of 326 patients
      in the atorvastatin group and 59 (18.7%) of 316 patients in the placebo group
      (hazard ratio [HR] 0.87, 95% CI 0.60-1.26, P=.46). No significant effect was
      observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%,
      respectively; HR 1.14, 95% CI 0.53-2.47, P=.74), nonfatal myocardial infarction
      (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P=.50), myocardial injury
      after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, P=.26), and
      stroke (0.9% vs 0%, P=.25). CONCLUSION: In contrast to the prior observational
      and trial data, the LOAD trial has neutral results and did not demonstrate a
      reduction in major cardiovascular complications after a short-term perioperative
      course of statin in statin-naive patients undergoing noncardiac surgery. We
      demonstrated, however, that a large multicenter blinded perioperative statin
      trial for high-risk statin-naive patients is feasible and should be done to
      definitely establish the efficacy and safety of statin in this patient
      population.

PMID- 27892895
TI  - Prothymosin-alpha and Ki-67 expression in pituitary adenomas.
AB  - INTRODUCTION: Prothymosin alpha (PTMA), a nuclear oncoprotein involved in cell
      cycle regulation, is used as a prognostic marker in many cancers. The
      histopathology of pituitary carcinomas and locally invasive adenomas is
      indistinguishable from that of benign tumors. A new marker is needed to
      differentiate these lesions. We evaluated PTMA in pituitary adenomas to determine
      its usefulness as a prognostic factor of tumor proliferation. MATERIAL/METHODS:
      We conducted a retrospective analysis of a group of 27 patients, including 15
      females (56%) and 12 males (44%) with a mean age of 58.6+/-12 years, who
      underwent pituitary tumor surgery between 2003 and 2012. The Ki-67 and PTMA
      nuclear (PTMA-n) and PTMA-cytoplasmic (PTMA-c) indices were determined by
      immunohistochemical staining. We studied histopathological features, clinical
      symptoms, and magnetic resonance imaging or computed tomography performed before
      surgery and one year following surgery to evaluate tumor size and progression.
      RESULTS: The expression of Ki-67 was revealed in 77.8% of adenomas, PTMA-n in
      81.5% and PTMA-c in 92.6%. The mean value of the Ki-67 index was 1.8%, PTMA-n was
      1.84%, and PTMA-c was 35.6%. There was a significant positive correlation between
      Ki-67 and PTMA-n (p=0.009). We did not find any correlation between Ki-67, PTMA
      c, and tumor progression. PTMA-n was found to be correlated with tumor size
      (p=0.045) and was higher in the case of gonadotropinomas (p=0.026). CONCLUSIONS:
      The positive nuclear expression of Ki-67 and PTMA was observed in the majority of
      pituitary adenomas. Neither the expression of Ki-67 nor that of PTMA-c was
      related to tumor recurrence or local invasion.

PMID- 27892897
TI  - The importance of selected spices in cardiovascular diseases.
AB  - Cardiovascular diseases are the leading cause of death worldwide. Literature data
      indicate that, due to these diseases, approximately 17.5 million people died in
      2012. Types of cardiovascular disease include ischemic heart disease,
      cerebrovascular disease, peripheral vascular disease, congenital heart disease,
      rheumatic heart disease, cardiomyopathy and arrhythmia. Proper nutrition is an
      important factor in reducing the risk of cardiovascular events. An interesting
      element of our diets is spices. For thousands of years, they have been used in
      the treatment of many diseases: bacterial infections, coughs, colds, and liver
      diseases. Many studies also demonstrate their antioxidant, chemopreventive, anti
      inflammatory and immunomodulatory properties. This paper focuses on discussing
      the importance of selected spices (garlic, cinnamon, ginger, coriander and
      turmeric) in the prevention and treatment of cardiovascular diseases.

PMID- 27892896
TI  - C-reactive protein as a diagnostic and prognostic factor in inflammatory bowel
      diseases.
AB  - AIM: The study aimed to evaluate high-sensitivity CRP (hsCRP) as a diagnostic and
      predictive marker in patients with inflammatory bowel disease (IBD).
      MATERIAL/METHODS: Medical history of 106 patients with IBD revealed hsCRP
      concentrations at diagnosis and during the follow-up period. RESULTS: The study
      showed that the majority of investigated patients had elevated hsCRP
      concentrations at diagnosis, although the mean concentration was much higher in
      the group of patients with Crohn's disease (CD) than the group with ulcerative
      colitis (UC) (P<0.001). The overall decrease in mean hsCRP concentration observed
      during the follow-up period was larger in the group of CD patients. The analysis
      showed a correlation between hsCRP concentrations at diagnosis and risk of
      surgery in the group of CD patients (r=0.408, P=0.002), but not in the group of
      UC patients. In a logistic regression analysis, surgery in CD patients was
      associated with age (OR: 0.89, 95% CI: 0.8-1.0, P=0.05) and hsCRP concentration
      (OR: 1.02, 95% CI: 1.0-1.04, P=0.03) at diagnosis. DISCUSSION: HsCRP might be a
      useful diagnostic marker in differentiating active IBD from other diseases.
      Particularly important however seems to be the predictive value of hsCRP at
      diagnosis in prognosing the clinical outcome of the disease in CD patients.

PMID- 27892898
TI  - The role of adipose tissue and excess of fatty acids in the induction of insulin
      resistance in skeletal muscle.
AB  - Skeletal muscle is the main tissue responsible for insulin-stimulated glucose
      uptake. Consumption of a high-fat diet rich in saturated fats (HFD) and obesity
      are associated with accumulation of intramuscular lipids that leads to several
      disorders, e.g. insulin resistance (IRes) and type 2 diabetes (T2D). The
      mechanism underlying the induction of IRes is still unknown. It was speculated
      that accumulation of intramuscular triacylglycerols (TAG) is linked to induction
      of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA),
      diacylglycerols (DAG) and ceramides (Cer). It has been demonstrated that
      accumulation of each of the above-mentioned lipid classes negatively affects the
      insulin signaling pathway. It is not clear which of those lipids play the most
      important role in HFD-induced skeletal muscle IRes. The aim of the present work
      is to present the current knowledge of the role of adipose tissue and excess of
      fatty acids in the induction of insulin resistance.

PMID- 27892899
TI  - Endogenous mechanisms of reactive oxygen species (ROS) generation.
AB  - The main cellular source of reactive oxygen species (ROS) is mitochondrial
      respiratory chain and active NADPH responsible for "respiratory burst" of
      phagocytes. Whatsmore ROS are produced in endoplasmic reticulum, peroxisomes,
      with the participation of xanthine and endothelial oxidase and during
      autoxidation process of small molecules. Mitochondrial respiratory chain is the
      main cellular source of ROS. It is considered that in aerobic organisms ROS are
      mainly formed during normal oxygen metabolism, as byproducts of oxidative
      phosphorylation, during the synthesis of ATP. The intermembranous phagocyte
      enzyme - activated NADPH oxidase, responsible for the "respiratory burst" of
      phagocytes, which is another source of ROS, plays an important role in defense of
      organism against infections. The aim of this article is to resume actuall
      knowledge about structure and function of the mitochondrial electron transport
      chain in which ROS are the byproducts and about NADPH oxidase as well as the
      function of each of its components in the "respiratory burst" of phagocytes.

PMID- 27892900
TI  - Integrating Telepresence Robots Into Nursing Simulation.
AB  - This article provides an overview of the use of telepresence robots in clinical
      practice and describes an evaluation of an educational project in which distance
      based nurse practitioner students used telepresence robots in clinical
      simulations with on-campus Accelerated Bachelor of Science in Nursing students.
      The results of this project suggest that the incorporation of telepresence in
      simulation is an effective method to promote engagement, satisfaction, and self
      confidence in learning.

PMID- 27892901
TI  - Designing a Virtual Simulation Case for Cultural Competence Using a Community
      Based Participatory Research Approach: A Puerto Rican Case.
AB  - In this study, a community-based participatory research approach was used for
      developing content for a virtual simulation case. The virtual simulation case was
      designed to develop the cultural competence of prelicensure nursing students in
      caring for a Puerto Rican patient with diabetes. This article presents the method
      used to establish a Puerto Rican community advisory board to develop content for
      a virtual simulation case for cultural competency.

PMID- 27892902
TI  - Committee Opinion No. 591: Challenges for Overweight and Obese Women: Correction.

PMID- 27892903
TI  - Committee Opinion No. 625: Management of Women With Dense Breasts Diagnosed by
      Mammography: Correction.

PMID- 27892904
TI  - Practice Bulletin No. 84: Prevention of Deep Vein Thrombosis and Pulmonary
      Embolism: Correction.

PMID- 27892905
TI  - Practice Bulletin No. 141: Management of Menopausal Symptoms: Correction.

PMID- 27892907
TI  - Concierge Medicine: A Viable Business Model for (Some) Physicians of the Future?
AB  - Concierge medicine is a medical management structure that has been in existence
      since the 1990s. Essentially, a typical concierge medical practice limits its
      number of patients and provides highly personalized attention that includes
      comprehensive annual physicals, same-day appointments, preventive and wellness
      care, and fast, 24/7 response time. Concierge medicine has become popular among
      both physicians and patients/consumers who are frustrated by the limitations
      imposed by managed care organizations. From many physicians' perspectives,
      concierge medicine offers greater autonomy, the opportunity to return to a more
      manageable patient load, and the chance to improve their incomes that have
      declined because of increasingly lowered reimbursements for their services. From
      many patients'/consumers' perspectives, concierge medicine provides more
      immediate, convenient, and caring access to their primary care physicians and,
      regardless of their physician's annual retainer fee, the elimination of third
      party insurance coverage costs and hassles. The major criticisms of the concierge
      medicine model come from some health care policy makers and experts, who believe
      that concierge medicine is elitist and its widespread implementation will
      increase the shortage of primary care physicians, which is already projected to
      become worse because of the Affordable Care Act's individual mandate, which
      requires everyone to have health insurance.Utilizing these topics as its
      framework, this article explains why concierge medicine's form of medical
      management is gaining ground, cites its advantages and disadvantages for
      stakeholders, and examines some of the issues that will affect its growth.

PMID- 27892906
TI  - From the Editor.

PMID- 27892908
TI  - Regional Interrelationships: A Leadership Opportunity for Health Care.
AB  - Given the impact that the health care industry has on the national economy,
      health care executives need to move beyond simply providing health care
      treatments and instead focus on strategically leading their regions, including
      the other key industry contributors in their specific regions. Geographic and
      economic regions can be viewed as concentric circles of influence, with each
      circle recognizing the resources and contributions that are specific to a region.
      An acknowledgement by health care executives of the regional interrelationships
      that exist in a specific region is necessary for health care managers to
      strategically lead regional interrelationships. A template for implementation of
      this process is included. To understand the various factors that exist within
      circles of influence, several distinct yet interrelated vertical bases of
      knowledge will be discussed. The 5 bases of knowledge examined here include the
      following: Health Care, Tourism, Defense and Technology, Education, and Retail.
      It is important to note that the resources identified in the Tourism, Defense and
      Technology, Education, and Retail knowledge bases all have a direct influential
      relationship upon the health care resources of the region. For description
      purposes, the Central Florida geographic and economic region will be examined for
      interrelationships between the 5 knowledge bases.

PMID- 27892909
TI  - Managing Patient Falls in Psychiatric Inpatient Units: Part 1.
AB  - The problem addressed in the current quantitative, descriptive study was the
      significantly higher number of patient falls in hospital inpatient psychiatric
      units than in medical-surgical areas, resulting in patient-safety issues. The
      purpose of this study was to explore psychiatric unit directors' perceptions of
      the factors that contribute to patient falls in the State of Michigan. Two
      research questions guided the study: (a) What are psychiatric unit directors'
      perceptions of the possible intrinsic factors that contribute to patient falls in
      the psychiatric inpatient units, and (b) what are psychiatric unit directors'
      perceptions of the possible extrinsic factors that contribute to patient falls in
      the psychiatric inpatient units? An online survey was the tool used to gather
      data from the State of Michigan psychiatric unit directors. The analyses for the
      2 questions indicated the participants believed that intrinsic factors were more
      strongly related to the likelihood of patient falls than were extrinsic factors.

PMID- 27892910
TI  - Contingency Management of Health Care Organizations: It Depends.
AB  - Managers in health care organizations (HCOs) must perform many processes and
      activities, such as planning goals, designing organization structure, leading
      people, motivating employees, making decisions, and resolving conflict. How they
      do all this strongly affects the performance and outcomes of their organizations
      and themselves. Some managers develop a usual way of performing their jobs and
      achieve some success with a preferred method of leading or a favorite approach to
      motivating. However, their success will be limited if they always rely on a
      standard "1-size-fits-all" approach. This is because contingency factors
      influence the effectiveness of a given approach to managing. The "best" approach
      depends on contingency factors, including the situation and the people involved.
      Managers should choose an approach to fit with the changing contingency factors.
      This article explains why and how managers should develop a contingency approach
      to managing HCOs. The development of contingency theory is briefly described.
      Practical application of contingency management is explained for leading,
      motivating, decision making, and resolving conflict. By using a contingency
      approach, managers can be more effective when managing their HCOs.

PMID- 27892911
TI  - Case in Health Care Management.

PMID- 27892912
TI  - Rightful Discharge: Making "Termination" Mean It Is Really Over: Part 1-Issues
      and Legislation.
AB  - One of the most difficult undertakings for any employer is carrying out a
      decision to terminate an employee. Of all the employment-related actions taken by
      employers, the act of termination creates the greatest risk of legal liability.
      Many claims of employment discrimination filed with the Equal Employment
      Opportunity Commission arise from the act of termination. In many federal courts,
      employment-related lawsuits account for more than 50% of all court filings; these
      lawsuits cover a wide range of subjects, such as failure to hire, defamation,
      breach of contract, and harassment, to name a few. However, most employees sue
      because they have lost their job or fear they will lose their job. Because these
      individuals have virtually nothing to lose, they often see filing a claim with
      the Equal Employment Opportunity Commission or filing a lawsuit as the only
      viable option-often suing for wrongful discharge. With a thoughtful review of the
      issues and the legislation addressed in this article, health care managers can
      reduce the unnecessary risk of expensive, time-consuming litigation.

PMID- 27892913
TI  - Developing a Successful Master of Health Administration Student Mentor-Mentee
      Program.
AB  - A student mentoring program can impact the overall experience in an academic
      program and establish a strong connection between students. It creates a platform
      for students to ask specific questions, learn more about the curriculum and
      professional opportunities, and compare tips on how to approach businesses for
      career-building positions. Topics such as conducting a residency search, finding
      an external mentor, and navigating through academic projects are often stressful
      components of the master of health administration (MHA) curriculum. This stress
      and confusion can be reduced by engaging students to actively communicate and
      utilize university resources through the mentor program. Future opportunities
      exist for growth and expansion of the mentor programs within an existing or newly
      established MHA program. Key factors to successful integration of the student
      mentor-mentee program are open communication and transparency between students,
      program chair, and faculty. This study compares past methods for implementing and
      running a mentor program, with newer program models. In addition, the various
      models of mentor programs will be discussed within the academic environment of an
      MHA program.

PMID- 27892915
TI  - Patient Access: Improving Wait Times in a Specialty Clinic.
AB  - A vascular surgery clinic in an academic center faced many delays for patients in
      gaining access to an appointment. In January 2014, wait times from referral to
      patient appointment were estimated to be 3 to 4 weeks. A 6-month pilot project
      was conducted from January 2014 through June 2014 with the aim of scheduling 50%
      of new patients within 7 days of referral. The clinic manager, medical director,
      clinic staff, and clerical team worked in partnership to initiate a series of
      interventions to reduce the backlog of patients, implement scheduling guidelines,
      and use nurse practitioners to improve practice efficiencies. By June 2014, the
      vascular surgery clinic achieved the goals of increased accommodation of new
      patients and a positive trend patient satisfaction comments as surveyed by Press
      Ganey. Performance outcomes in both areas were sustained for 6 consecutive
      months.

PMID- 27892914
TI  - The Effects of Transformational Leadership and Mediating Factors on the
      Organizational Success Using Structural Equation Modeling: A Case Study.
AB  - This study was undertaken to determine the effects of transformational leadership
      (TL) and mediating factors on organizational success (OS) from the
      administrative, financial, and support employees' perspective in teaching
      hospitals affiliated with Shiraz University of Medical Sciences using structural
      equation modeling. Three hundred administrative and financial employees were
      selected, using stratified sampling proportional to size and simple random
      sampling. Data were collected using 5 questionnaires and analyzed using SPSS 21.0
      and Lisrel 8.5 through Pearson correlation coefficient and path analysis and
      confirmatory factor analysis methods. Results showed that TL had significant
      positive effects on the 3 mediating factors, including organizational culture (t
      = 15.31), organizational citizenship behavior (OCB) (t = 10.06), and social
      capital (t = 10.25). Also, the organizational culture (t = 2.26), OCB (t = 3.48),
      and social capital (t = 7.41) had significant positive effects on OS. According
      to the results, TL had an indirect effect on OS. Therefore, organizations can
      achieve more success by strengthening organizational culture, OCB, and social
      capital through using transformational leadership style. Therefore, in order to
      increase OS, the following recommendations are made: supporting and encouraging
      new ideas in the organization, promoting teamwork, strengthening intergroup and
      intragroup relationships, planning to strengthen and enrich the social and
      organizational culture, considering the promotion of social capital in the
      employee training, establishing a system to give rewards to the employees
      performing extra-role activities, providing a suitable environment for creative
      employees, and so on.

PMID- 27892916
TI  - Deciding to Decide: How Decisions Are Made and How Some Forces Affect the
      Process.
AB  - There is a decision-making pattern that applies in all situations, large or
      small, although in small decisions, the steps are not especially evident. The
      steps are gathering information, analyzing information and creating alternatives,
      selecting and implementing an alternative, and following up on implementation.
      The amount of effort applied in any decision situation should be consistent with
      the potential consequences of the decision. Essentially, all decisions are
      subject to certain limitations or constraints, forces, or circumstances that
      limit one's range of choices. Follow-up on implementation is the phase of
      decision making most often neglected, yet it is frequently the phase that
      determines success or failure. Risk and uncertainty are always present in a
      decision situation, and the application of human judgment is always necessary. In
      addition, there are often emotional forces at work that can at times unwittingly
      steer one away from that which is best or most workable under the circumstances
      and toward a suboptimal result based largely on the desires of the decision
      maker.

PMID- 27892917
TI  - Adjunctive Social Media for More Effective Contraceptive Counseling: A Randomized
      Controlled Trial: Correction.

PMID- 27892919
TI  - Practice Bulletin No. 165 Summary: Prevention and Management of Obstetric
      Lacerations at Vaginal Delivery: Correction.

PMID- 27892918
TI  - Effect of Diaphragm and Lubricant Gel Provision on Human Papillomavirus Infection
      Among Women Provided With Condoms: A Randomized Controlled Trial: Correction.

PMID- 27892920
TI  - FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in
      colorectal cancer.
AB  - The transcriptional factor Forkhead box k1 (FOXK1) is a member of the FOX family.
      The abnormal expression of FOXK1 may have an important role in tumour
      development. Our previous studies showed that four-and-a-half LIM protein 2
      (FHL2) is a critical inducer of the epithelial-to-mesenchymal transition (EMT)
      and invasion. However, the molecular mechanism by which FOXK1 synergizes with
      FHL2 tumour proliferation, EMT and metastasis is not well defined. We evaluated
      that messenger RNA (mRNA) and protein expression levels by quantitative RT-PCR,
      western blot, immunofluorescence and immunohistochemistry (IHC) assays. The
      migration and invasive abilities of colorectal cancer (CRC) cells were evaluated
      using short hairpin RNA (shRNA)-mediated inhibition in vitro and in vivo. We
      showed that FOXK1 expression was upregulated in CRC compared with matched normal
      tissues. FOXK1 physically interacts with FHL2 in CRC. Moreover, higher expression
      levels of the two proteins were significantly associated with differentiation,
      lymph node metastasis, AJCC stage and poorer prognosis. Furthermore, the
      overexpression of FOXK1 in CRC cells is associated with EMT, invasion and
      metastasis. However, the siRNA-mediated repression of FHL2 in FOXK1
      overexpressing cells reversed EMT and both the proliferative and metastatic
      phenotypes in vitro and in vivo. These data identified that the co-expression of
      FOXK1 and FHL2 enhances cell proliferation and metastasis through the induction
      of EMT. Thus, FOXK1 and FHL2 may serve as putative targets in the combined
      therapy of CRC.

PMID- 27892921
TI  - An essential role for bacterial nitric oxide synthase in Staphylococcus aureus
      electron transfer and colonization.
AB  - Nitric oxide (NO*) is a ubiquitous molecular mediator in biology. Many signalling
      actions of NO* generated by mammalian NO* synthase (NOS) result from targeting of
      the haem moiety of soluble guanylate cyclase. Some pathogenic and environmental
      bacteria also produce a NOS that is evolutionary related to the mammalian
      enzymes, but a bacterial haem-containing receptor for endogenous enzymatically
      generated NO* has not been identified previously. Here, we show that NOS of the
      human pathogen Staphylococcus aureus, in concert with an NO*-metabolizing
      flavohaemoprotein, regulates electron transfer by targeting haem-containing
      cytochrome oxidases under microaerobic conditions to maintain membrane
      bioenergetics. This process is essential for staphylococcal nasal colonization
      and resistance to the membrane-targeting antibiotic daptomycin and demonstrates
      the conservation of NOS-derived NO*-haem receptor signalling between bacteria and
      mammals.

PMID- 27892922
TI  - Convergence and divergence of bitterness biosynthesis and regulation in
      Cucurbitaceae.
AB  - Differentiation of secondary metabolite profiles in closely related plant species
      provides clues for unravelling biosynthetic pathways and regulatory circuits, an
      area that is still underinvestigated. Cucurbitacins, a group of bitter and highly
      oxygenated tetracyclic triterpenes, are mainly produced by the plant family
      Cucurbitaceae. These compounds have similar structures, but differ in their
      antitumour activities and ecophysiological roles. By comparative analyses of the
      genomes of cucumber, melon and watermelon, we uncovered conserved syntenic loci
      encoding metabolic genes for distinct cucurbitacins. Characterization of the
      cytochrome P450s (CYPs) identified from these loci enabled us to unveil a novel
      multi-oxidation CYP for the tailoring of the cucurbitacin core skeleton as well
      as two other CYPs responsible for the key structural variations among
      cucurbitacins C, B and E. We also discovered a syntenic gene cluster of
      transcription factors that regulates the tissue-specific biosynthesis of
      cucurbitacins and may confer the loss of bitterness phenotypes associated with
      convergent domestication of wild cucurbits. This study illustrates the potential
      to exploit comparative genomics to identify enzymes and transcription factors
      that control the biosynthesis of structurally related yet unique natural
      products.

PMID- 27892924
TI  - The pattern-recognition receptor CORE of Solanaceae detects bacterial cold-shock
      protein.
AB  - Plants and animals recognize microbial invaders by detecting microbe-associated
      molecular patterns (MAMPs) by cell surface receptors. Many plant species of the
      Solanaceae family detect the highly conserved nucleic acid binding motif RNP-1 of
      bacterial cold-shock proteins (CSPs), represented by the peptide csp22, as a
      MAMP. Here, we exploited the natural variation in csp22 perception observed
      between cultivated tomato (Solanum lycopersicum) and Solanum pennellii to map and
      identify the leucine-rich repeat (LRR) receptor kinase CORE (cold shock protein
      receptor) of tomato as the specific, high-affinity receptor site for csp22.
      Corroborating its function as a genuine receptor, heterologous expression of CORE
      in Arabidopsis thaliana conferred full sensitivity to csp22 and, importantly, it
      also rendered these plants more resistant to infection by the bacterial pathogen
      Pseudomonas syringae pv. tomato DC3000. Our study also confirms the
      biotechnological potential of enhancing plant immunity by interspecies transfer
      of highly effective pattern-recognition receptors such as CORE to different plant
      families.

PMID- 27892923
TI  - Origin and function of stomata in the moss Physcomitrella patens.
AB  - Stomata are microscopic valves on plant surfaces that originated over 400 million
      years (Myr) ago and facilitated the greening of Earth's continents by permitting
      efficient shoot-atmosphere gas exchange and plant hydration1. However, the core
      genetic machinery regulating stomatal development in non-vascular land plants is
      poorly understood2-4 and their function has remained a matter of debate for a
      century5. Here, we show that genes encoding the two basic helix-loop-helix
      proteins PpSMF1 (SPEECH, MUTE and FAMA-like) and PpSCREAM1 (SCRM1) in the moss
      Physcomitrella patens are orthologous to transcriptional regulators of stomatal
      development in the flowering plant Arabidopsis thaliana and essential for stomata
      formation in moss. Targeted P. patens knockout mutants lacking either PpSMF1 or
      PpSCRM1 develop gametophytes indistinguishable from wild-type plants but mutant
      sporophytes lack stomata. Protein-protein interaction assays reveal
      heterodimerization between PpSMF1 and PpSCRM1, which, together with moss
      angiosperm gene complementations6, suggests deep functional conservation of the
      heterodimeric SMF1 and SCRM1 unit is required to activate transcription for moss
      stomatal development, as in A. thaliana7. Moreover, stomata-less sporophytes of
      DeltaPpSMF1 and DeltaPpSCRM1 mutants exhibited delayed dehiscence, implying
      stomata might have promoted dehiscence in the first complex land-plant
      sporophytes.

PMID- 27892926
TI  - Dual-specificity phosphatase 6 deficiency regulates gut microbiome and
      transcriptome response against diet-induced obesity in mice.
AB  - The gut microbiota plays profound roles in host metabolism and the inflammatory
      response associated with the development of obesity. Dusp6-deficient mice have
      been shown to be resistant to diet-induced obesity, but the mechanism behind this
      remains unclear. 16S ribosomal RNA gene analysis demonstrated that dusp6
      deficient mice harbour unique gut microbiota with resistance to diet-induced
      obesity-mediated alteration of the gut microbiome. Using a germ-free mouse model,
      we found that faecal/gut microbiota derived from dusp6-deficient mice
      significantly increased energy expenditure and reduced weight gain in recipient
      wild-type mice fed on a high-fat diet. On analysis of the intestinal
      transcriptome of dusp6-deficient mice, we found that dusp6 deficiency mainly
      induced biological processes involved in metabolism and the extracellular matrix,
      particularly the peroxisome proliferator-activated receptor gamma (Ppargamma)
      pathway and tight-junction genes. Furthermore, dusp6-deficient mice have a high
      fat-diet-specific transcriptomic response to reverse the expression of genes
      associated with intestinal barrier functions and mucosal immunity involved in
      microbiome homeostasis. This study demonstrates that dusp6 deficiency is a strong
      genetic factor shaping gut microbiota, and that it confers obesity protection by
      ameliorating the gut microbiota response to diet-mediated stress.

PMID- 27892927
TI  - Photosynthesis: Mining grasses for a better Rubisco.

PMID- 27892925
TI  - A mouse model for MERS coronavirus-induced acute respiratory distress syndrome.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel virus that
      emerged in 2012, causing acute respiratory distress syndrome (ARDS), severe
      pneumonia-like symptoms and multi-organ failure, with a case fatality rate of
      ~36%. Limited clinical studies indicate that humans infected with MERS-CoV
      exhibit pathology consistent with the late stages of ARDS, which is reminiscent
      of the disease observed in patients infected with severe acute respiratory
      syndrome coronavirus. Models of MERS-CoV-induced severe respiratory disease have
      been difficult to achieve, and small-animal models traditionally used to
      investigate viral pathogenesis (mouse, hamster, guinea-pig and ferret) are
      naturally resistant to MERS-CoV. Therefore, we used CRISPR-Cas9 gene editing to
      modify the mouse genome to encode two amino acids (positions 288 and 330) that
      match the human sequence in the dipeptidyl peptidase 4 receptor, making mice
      susceptible to MERS-CoV infection and replication. Serial MERS-CoV passage in
      these engineered mice was then used to generate a mouse-adapted virus that
      replicated efficiently within the lungs and evoked symptoms indicative of severe
      ARDS, including decreased survival, extreme weight loss, decreased pulmonary
      function, pulmonary haemorrhage and pathological signs indicative of end-stage
      lung disease. Importantly, therapeutic countermeasures comprising MERS-CoV
      neutralizing antibody treatment or a MERS-CoV spike protein vaccine protected the
      engineered mice against MERS-CoV-induced ARDS.

PMID- 27892928
TI  - Microfluidics-assisted fluorescence in situ hybridization for advantageous human
      epidermal growth factor receptor 2 assessment in breast cancer.
AB  - Fluorescence in situ hybridization (FISH) is one of the recommended techniques
      for human epidermal growth factor receptor 2 (HER2) status assessment on cancer
      tissues. Here we develop microfluidics-assisted FISH (MA-FISH), in which
      hybridization of the FISH probes with their target DNA strands is obtained by
      applying square-wave oscillatory flows of diluted probe solutions in a thin
      microfluidic chamber of 5 MUl volume. By optimizing the experimental parameters,
      MA-FISH decreases the consumption of the expensive probe solution by a factor 5
      with respect to the standard technique, and reduces the hybridization time to 4
      h, which is four times faster than in the standard protocol. To validate the
      method, we blindly conducted HER2 MA-FISH on 51 formalin-fixed paraffin-embedded
      tissue slides of 17 breast cancer samples, and compared the results with standard
      HER2 FISH testing. HER2 status classification was determined according to
      published guidelines, based on average number of HER2 copies per cell and average
      HER2/CEP17 ratio. Excellent agreement was observed between the two methods,
      supporting the validity of MA-FISH and further promoting its short hybridization
      time and reduced reagent consumption.

PMID- 27892929
TI  - A review of kinase fusions in melanocytic tumors.
AB  - Translocations resulting in a kinase fusion are well reported in many tumor types
      and indeed can be defining, particularly in the case of hematopoietic
      malignancies. The recent reports of multiple protein kinase fusions within
      melanocytic neoplasms, particularly in those with spitzoid morphology, have
      heralded a new era of classification of these melanocytic tumors. Seen within
      approximately half of all spitzoid neoplasms and present within the full spectrum
      of benign, atypical, and malignant lesions, kinase fusions likely represent an
      early oncogenic event contributing to cell proliferation and growth. Although the
      presence of a kinase fusion does not seem to correlate with the biologic
      potential of a given lesion, documentation of a kinase fusion will likely be
      important, particularly in the case of spitzoid melanoma, as numerous specific
      kinase receptor inhibitors have shown promise as therapeutic agents in a subset
      of cases with kinase fusions. Interrogation of non-spitzoid melanomas for similar
      kinase fusions as a potential driving oncogenic mechanism has revealed some
      similarities and some differences. This review will focus on the kinase fusions
      described to date in spitzoid neoplasms and how subsequent studies have informed
      current melanoma research.

PMID- 27892930
TI  - An optimized protocol for purification of functional islets of Langerhans.
AB  - Islets of Langerhans and beta-cell isolation constitute routinely used cell
      models for diabetic research, and refining islet isolation protocols and cell
      quality assessment is a high priority. Numerous protocols have been published
      describing isolate of islets, but often rigorous and systematic assessment of
      their integrity is lacking. Herein, we propose a new protocol for optimal
      generation of islets. Pancreases from mice and rats were excised and digested
      using a low-activity collagenase solution and islets were then purified by a
      series of sedimentations and a Percoll gradient. Islets were maintained in
      culture for 5 days, during which viability, pro/antiapoptotic, and islet-specific
      genes, glucose-stimulated calcium entry, glucose uptake, and insulin secretion
      were assessed. The commonly used islet isolation technique by collagenase
      injection through the common bile duct (CBD) was also performed and compared with
      the present approach. This new protocol produced islets that retained a healthy
      status as demonstrated by the yield of stable living cells. Furthermore, calcium
      oscillation, glucose uptake, and insulin secretion remained intact in the islet
      cultures. This was reproducible when many rodent species were used, and neither
      sex nor age affected the cells behavior. When compared with the CBD technique,
      islet physiology was similar. Finally, this approach was used to uncover new ion
      channel candidates implicated in insulin secretion. In conclusion, this study
      outlines an efficient protocol for islet preparation that may support research
      into new therapeutic targets in diabetes research.

PMID- 27892931
TI  - The influence of tumor regression, solar elastosis, and patient age on
      pathologists' interpretation of melanocytic skin lesions.
AB  - It is not known whether patient age or tumor characteristics such as tumor
      regression or solar elastosis influence pathologists' interpretation of
      melanocytic skin lesions (MSLs). We undertook a study to determine the influence
      of these factors, and to explore pathologist's characteristics associated with
      the direction of diagnosis. To meet our objective, we designed a cross-sectional
      survey study of pathologists' clinical practices and perceptions. Pathologists
      were recruited from diverse practices in 10 states in the United States. We
      enrolled 207 pathologist participants whose practice included the interpretation
      of MSLs. Our findings indicated that the majority of pathologists (54.6%) were
      influenced toward a less severe diagnosis when patients were <30 years of age.
      Most pathologists were influenced toward a more severe diagnosis when patients
      were >70 years of age, or by the presence of tumor regression or solar elastosis
      (58.5%, 71.0%, and 57.0%, respectively). Generally, pathologists with
      dermatopathology board certification and/or a high caseload of MSLs were more
      likely to be influenced, whereas those with more years' experience interpreting
      MSL were less likely to be influenced. Our findings indicate that the
      interpretation of MSLs is influenced by patient age, tumor regression, and solar
      elastosis; such influence is associated with dermatopathology training and higher
      caseload, consistent with expertise and an appreciation of lesion complexity.

PMID- 27892933
TI  - Parity-time-symmetric circular Bragg lasers: a proposal and analysis.
AB  - We propose a new type of semiconductor lasers by implementing the concept of
      parity-time symmetry in a two-dimensional circular Bragg grating structure, where
      both the real and imaginary parts of the refractive index are modulated along the
      radial direction. The laser modal properties are analyzed with a transfer-matrix
      method and are verified with numerical simulation of a practical design. Compared
      with conventional distributed-feedback lasers with modulation of only the real
      part of refractive index, the parity-time-symmetric circular Bragg lasers feature
      reduced threshold and enhanced modal discrimination, which in combination with
      the intrinsic circularly symmetric, large emission aperture are clear advantages
      in applications that require mode-hop-free, high-power, single-mode laser
      operation.

PMID- 27892934
TI  - Treatment with FGFR2-IIIc monoclonal antibody suppresses weight gain and
      adiposity in KKAy mice.
AB  - Expression of beta-Kotho, fibroblast growth factor receptor (FGFR)-1c and 2c,
      which bind FGF21, is decreased in the white adipose tissue of obese mice. The aim
      of the present study was to determine the role of FGFR2c in the development of
      obesity and diabetes in KKAy mice. Treatment with mouse monoclonal FGFR2-IIIc
      antibody (0.5 mg kg-1) significantly suppressed body weight gain and epididymal
      white adipose tissue weight in individually housed KKAy mice while having no
      effect on daily food intake. In addition, treatment with FGFR2-IIIc antibody
      significantly increased plasma-free fatty acid levels while having no effect on
      blood glucose or plasma FGF21 levels. Moreover, treatment with FGFR2-IIIc
      antibody had no significant effect on the expression of uncoupling protein-1,
      uncoupling protein-2 or peroxisome proliferator-activated receptor-gamma
      coactivator 1alpha in the epididymal white adipose tissue. The treatment with
      FGFR2-IIIc antibody had no significant effects on daily food intake and body
      weight gain in individually housed KK mice. These findings suggest that FGFR2
      IIIc upregulates the adiposity induced by social isolation in KKAy mice, and that
      decreased expression and/or function of FGFR2c might be a compensatory response
      to enhanced adiposity. Inhibition of FGFR2-IIIc function might be a novel
      therapeutic approach for obesity.

PMID- 27892932
TI  - Reciprocal regulation of carbon monoxide metabolism and the circadian clock.
AB  - Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a
      wide range of physiological, metabolic and behavioral processes. Feedback of
      metabolic signals, such as redox state, NAD+/NADH and AMP/ADP ratios, or heme,
      modulate circadian rhythms and thereby optimize energy utilization across the 24
      h cycle. We show that rhythmic heme degradation, which generates the signaling
      molecule carbon monoxide (CO), is required for normal circadian rhythms as well
      as circadian metabolic outputs. CO suppresses circadian transcription by
      attenuating CLOCK-BMAL1 binding to target promoters. Pharmacological inhibition
      or genetic depletion of CO-producing heme oxygenases abrogates normal daily
      cycles in mammalian cells and Drosophila. In mouse hepatocytes, suppression of CO
      production leads to a global upregulation of CLOCK-BMAL1-dependent circadian gene
      expression and dysregulated glucose metabolism. Together, our findings show that
      CO metabolism is an important link between the basic circadian-clock machinery,
      metabolism and behavior.

PMID- 27892935
TI  - The link between soda intake and asthma: science points to the high-fructose corn
      syrup, not the preservatives: a commentary.
AB  - Recent research conducted by investigators at the National Center for Chronic
      Disease Prevention and Health Promotion-a division of the US Centers for Disease
      Control and Prevention (CDC)-found that 'Regular-Soda Intake, Independent of
      Weight Status, is Associated with Asthma among US High School Students.' On the
      basis of their review of prior studies, researchers hypothesized that the
      association may be due to high intake of sodium benzoate, a commonly used
      preservative in US soft drinks. But a closer look at these prior research studies
      suggests that there is no strong scientific evidence that the preservatives in US
      soft drinks are associated with asthma. Importantly, other recent research
      suggests that the association may be with the unpaired (excess free) fructose in
      high fructose corn syrup.

PMID- 27892936
TI  - Influence of early life exposure, host genetics and diet on the mouse gut
      microbiome and metabolome.
AB  - Although the gut microbiome plays important roles in host physiology, health and
      disease1, we lack understanding of the complex interplay between host genetics
      and early life environment on the microbial and metabolic composition of the gut.
      We used the genetically diverse Collaborative Cross mouse system2 to discover
      that early life history impacts the microbiome composition, whereas dietary
      changes have only a moderate effect. By contrast, the gut metabolome was shaped
      mostly by diet, with specific non-dietary metabolites explained by microbial
      metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL)
      that impact the abundances of specific microbes. Human orthologues of genes in
      the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes
      located in mouse QTL for Lactobacillales abundance are implicated in arthritis,
      rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was
      predictive of higher host T-helper cell counts, suggesting an important link
      between Lactobacillales and host adaptive immunity.

PMID- 27892937
TI  - Novel recombinant papillomavirus genomes expressing selectable genes.
AB  - Papillomaviruses infect and replicate in keratinocytes, but viral proteins are
      initially expressed at low levels and there is no effective and quantitative
      method to determine the efficiency of infection on a cell-to-cell basis. Here we
      describe human papillomavirus (HPV) genomes that express marker proteins
      (antibiotic resistance genes and Green Fluorescent Protein), and can be used to
      elucidate early stages in HPV infection of primary keratinocytes. To generate
      these recombinant genomes, the late region of the oncogenic HPV18 genome was
      replaced by CpG free marker genes. Insertion of these exogenous genes did not
      affect early replication, and had only minimal effects on early viral
      transcription. When introduced into primary keratinocytes, the recombinant marker
      genomes gave rise to drug-resistant keratinocyte colonies and cell lines, which
      maintained the extrachromosomal recombinant genome long-term. Furthermore, the
      HPV18 "marker" genomes could be packaged into viral particles (quasivirions) and
      used to infect primary human keratinocytes in culture. This resulted in the
      outgrowth of drug-resistant keratinocyte colonies containing replicating HPV18
      genomes. In summary, we describe HPV18 marker genomes that can be used to
      quantitatively investigate many aspects of the viral life cycle.

PMID- 27892939
TI  - Postoperative survival According to the Glasgow PrognosticScore in Patients with
      Resected Lung Adenocarcinoma
AB  - Background: The Glasgow Prognostic Score (GPS) is calculated from measured CRP
      and albumin levels. We hereevaluated the significance of the GPS in patients with
      resected pulmonary adenocarcinoma. Materials and Methods:The present study
      included 156 patients with lung adenocarcinoma who underwent lobectomy at
      Kanazawa MedicalUniversity between 2002 and 2012. Classification was into three
      groups: those with normal albumin (>=3.5 g/dl) andC-reactive protein (CRP) (<=1.0
      mg/dl) levels were classified as GPS 0 (n =136), those with low albumin (<3.5
      g/dl) or elevated CRP (>1.0 mg/dl) levels as GPS 1 (n = 16), and those with low
      albumin (<3.5 g/dl) and elevated CRP(>1.0 mg/dl) levels as GPS 2 (n = 4). We
      retrospectively investigated relationships between the patient
      characteristicsincluding the GPS, and disease-free survival and cancer-specific
      survival. Results: The pathological stages of thepatients were as follows: IA
      (n=78, 50%), IB (n=31, 19.9%), IIA (n=20.0, 12.8%), IIB (n=9.0, 5.7%), and IIIA
      (n=18.0,11.5%). Lobectomy was performed in all cases. The average GPS was 0.15 (0
      2) and showed significant relationshipswith stage and tumor size. The 2-year
      survival rates in patients with GPS0, 1 and 2 were 81.4%, 38.4%, and
      25.0%,respectively. Clear correlations were noted with both cancer-specific
      survival and disease-free survival. Furthermore,multivariate analysis revealed
      that GPS was a significant prognostic factor. Conclusions: The GPS could be a
      prognosticfactor for patients with resected pulmonary adenocarcinoma.

PMID- 27892940
TI  - Robustness and Vulnerability of Networks with Dynamical Dependency Groups.
AB  - The dependency property and self-recovery of failure nodes both have great
      effects on the robustness of networks during the cascading process. Existing
      investigations focused mainly on the failure mechanism of static dependency
      groups without considering the time-dependency of interdependent nodes and the
      recovery mechanism in reality. In this study, we present an evolving network
      model consisting of failure mechanisms and a recovery mechanism to explore
      network robustness, where the dependency relations among nodes vary over time.
      Based on generating function techniques, we provide an analytical framework for
      random networks with arbitrary degree distribution. In particular, we
      theoretically find that an abrupt percolation transition exists corresponding to
      the dynamical dependency groups for a wide range of topologies after initial
      random removal. Moreover, when the abrupt transition point is above the failure
      threshold of dependency groups, the evolving network with the larger dependency
      groups is more vulnerable; when below it, the larger dependency groups make the
      network more robust. Numerical simulations employing the Erdos-Renyi network and
      Barabasi-Albert scale free network are performed to validate our theoretical
      results.

PMID- 27892938
TI  - Dendritic cell function and pathogen-specific T cell immunity are inhibited in
      mice administered levonorgestrel prior to intranasal Chlamydia trachomatis
      infection.
AB  - The growing popularity of levonorgestrel (LNG)-releasing intra-uterine systems
      for long-acting reversible contraception provides strong impetus to define
      immunomodulatory properties of this exogenous progestin. In initial in vitro
      studies herein, we found LNG significantly impaired activation of human dendritic
      cell (DCs) and their capacity to promote allogeneic T cell proliferation. In
      follow-up studies in a murine model of intranasal Chlamydia trachomatis
      infection, we analogously found that LNG treatment prior to infection
      dramatically reduced CD40 expression in DCs isolated from draining lymph nodes at
      2 days post infection (dpi). At 12 dpi, we also detected significantly fewer CD4+
      and CD8+ T cells in the lungs of LNG-treated mice. This inhibition of DC
      activation and T cell expansion in LNG-treated mice also delayed chlamydial
      clearance and the resolution of pulmonary inflammation. Conversely, administering
      agonist anti-CD40 monoclonal antibody to LNG-treated mice at 1 dpi restored lung
      T cell numbers and chlamydial burden at 12 dpi to levels seen in infected
      controls. Together, these studies reveal that LNG suppresses DC activation and
      function, and inhibits formation of pathogen-specific T cell immunity. They also
      highlight the need for studies that define in vivo effects of LNG use on human
      host response to microbial pathogens.

PMID- 27892941
TI  - Hatching asynchrony vs. foraging efficiency: the response to food availability in
      specialist vs. generalist tit species.
AB  - Breeding mistiming is increasingly frequent in several ecosystems in the face of
      current climate change. Species belonging to higher trophic levels must employ
      mechanisms to reduce it. One of these mechanisms is hatching asynchrony, with the
      eggs in a clutch hatching over a period of several days. Some authors have
      suggested it to be adaptive when food is unpredictable. However, these birds can
      also suffer associated costs. We tested whether a species with higher foraging
      efficiency avoid hatching asynchrony compared to its sister species. We studied
      hatching asynchrony and nestling provisioning in relation to food availability in
      sympatric populations of blue and great tits. For the first time, we show that
      sister species respond to food availability with different strategies. Blue tit
      feeding rates readily responded to the abundance of their main prey, and also
      reduced the impact of nestling size hierarchy on mean nestling weight,
      consequently increasing fledging rate. Our results suggest that levels of
      hatching asynchrony seem to be influenced by species-specific life history
      traits, as generalist foragers rely less on it. They also highlight the
      importance of multi-species approaches when studying the response of organisms to
      environmental unpredictability.

PMID- 27892942
TI  - Scattering of nanowire surface plasmons coupled to quantum dots with azimuthal
      angle difference.
AB  - Coherent scatterings of surface plasmons coupled to quantun dots have attracted
      great attention in plasmonics. Recently, an experiment has shown that the quantum
      dots located nearby a nanowire can be separated not only in distance, but also an
      angle phi along the cylindrical direction. Here, by using the real-space
      Hamiltonian and the transfer matrix method, we analytically obtain the
      transmission/reflection spectra of nanowire surface plasmons coupled to quantum
      dots with an azimuthal angle difference. We find that the scattering spectra can
      show completely different features due to different positions and azimuthal
      angles of the quantum dots. When additionally coupling a cavity to the dots, we
      obtain the Fano-like line shape in the transmission and reflection spectra due to
      the interference between the localized and delocalized modes.

PMID- 27892943
TI  - Temperature responses of Rubisco from Paniceae grasses provide opportunities for
      improving C3 photosynthesis.
AB  - Enhancing the catalytic properties of the CO2-fixing enzyme Rubisco is a target
      for improving agricultural crop productivity. Here, we reveal extensive diversity
      in the kinetic response between 10 and 37  degrees C by Rubisco from C3 and C4
      species within the grass tribe Paniceae. The CO2 fixation rate (kcatc) for
      Rubisco from the C4 grasses with nicotinamide adenine dinucleotide (NAD)
      phosphate malic enzyme (NADP-ME) and phosphoenolpyruvate carboxykinase (PCK)
      photosynthetic pathways was twofold greater than the kcatc of Rubisco from NAD-ME
      species across all temperatures. The declining response of CO2/O2 specificity
      with increasing temperature was less pronounced for PCK and NADP-ME Rubisco,
      which would be advantageous in warmer climates relative to the NAD-ME grasses.
      Modelled variation in the temperature kinetics of Paniceae C3 Rubisco and PCK
      Rubisco differentially stimulated C3 photosynthesis relative to tobacco above and
      below 25  degrees C under current and elevated CO2. Amino acid substitutions in
      the large subunit that could account for the catalytic variation among Paniceae
      Rubisco are identified; however, incompatibilities with Paniceae Rubisco
      biogenesis in tobacco hindered their mutagenic testing by chloroplast
      transformation. Circumventing these bioengineering limitations is critical to
      tailoring the properties of crop Rubisco to suit future climates.

PMID- 27892945
TI  - Therapy of pediatric ALL relapsing after allogeneic transplant: how to make
      progress with limited patient numbers?

PMID- 27892944
TI  - Veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic stem
      cell transplantation: Middle East/North Africa regional consensus on prevention,
      diagnosis and management.
AB  - Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) of the liver is
      a serious, early complication of haematopoietic stem cell transplantation (HSCT),
      severe and very severe forms of which are associated with a high mortality rate.
      A wide variety of patient, disease and treatment-related risk factors for VOD/SOS
      have been identified. Several bodies have published recommendations for the
      diagnosis, prevention and management of VOD/SOS following HSCT. A group of
      regional experts have developed a consensus statement on the diagnosis,
      prevention and management of VOD/SOS in the Middle East and North Africa region
      to help in the management of HSCT patients in the region. Risk factors of
      particular relevance in the region include iron overload in thalassaemia
      patients, some hereditary metabolic disorders due to consanguinity and infection
      with hepatitis virus B or C. Recommendations include diagnosis of VOD/SOS based
      on established clinical criteria, prophylaxis with defibrotide and/or
      ursodeoxycholic acid in patients at increased risk of VOD/SOS, and treatment with
      defibrotide for patients with severe/very severe VOD/SOS (and, if clinically
      indicated, in those with moderate or rapidly progressing VOD/SOS, as per the new
      European Society for Blood and Marrow Transplantation classification).

PMID- 27892947
TI  - Danaparoid reduces the incidence of hematopoietic stem cell transplantation
      associated thrombotic microangiopathy.

PMID- 27892946
TI  - First-line escalated BEACOPP does not hinder stem cell collection and
      transplantation strategy in patients with relapsed/refractory Hodgkin's lymphoma.

PMID- 27892948
TI  - Long-term outcomes after thiotepa-based high-dose therapy (HDT) and autologous
      hematopoietic cell transplantation (auto-HCT) in non-Hodgkin lymphoma (NHL).

PMID- 27892949
TI  - The EBMT-ELN working group recommendations on the prophylaxis and treatment of
      GvHD: a change-control analysis.
AB  - In 2013, recommendations for a standardized practice in the prophylaxis and
      treatment of GvHD were adopted and published by the European Society for Blood
      and Marrow Transplantation and the European LeukemiaNet. One year later, all 341
      European Society for Blood and Marrow Transplantation centres performing
      allogeneic haematopoietic stem cell transplantation were contacted for a change
      control analysis and asked to fill in a questionnaire; 111 centres (33%)
      responded. Of these, 83% had been aware of the recommendations. Paediatric
      centres (P=0.004), centres with shorter programme duration (P=0.049), not JACIE
      (the Joint Accreditation Committee of the International Society for Cellular
      Therapy and the European Society for Blood and Marrow Transplantation)-accredited
      centres (P=0.010) and centres from middle-income countries (P=0.033) were more
      likely to be unaware of the recommendations. Thirty-eight per cent of the centres
      regarded the recommendations as relevant guidelines affecting their policies, 61%
      as interesting information. Thirty per cent had decided to make changes in their
      institutional protocols based on the recommendations. More than 80% were willing
      to use the recommendations for a control arm in randomized studies. This survey
      shows that the published recommendations had some, though insufficient, impact on
      the strategies and methods of allogeneic haematopoietic stem cell transplantation
      applied by the centres. It also identified some of the weaknesses to be addressed
      when releasing recommendations in the future.

PMID- 27892950
TI  - PD-1 checkpoint blockade in patients with relapsed AML after allogeneic stem cell
      transplantation.

PMID- 27892951
TI  - Comparison of three or fewer high-dose chemotherapy cycles as salvage treatment
      in germ cell tumors in first relapse.

PMID- 27892952
TI  - Dynamic prognostic value of the revised international prognostic scoring system
      following pretransplant hypomethylating treatment in myelodysplastic syndrome.
AB  - This study aimed to analyze the use of the revised International Prognostic
      Scoring System (IPSS-R) assessed after hypomethylating treatment (HMT) for
      patients with myelodysplastic syndrome (MDS) undergoing an allogeneic stem cell
      transplantation (SCT). Among 115 patients who received pre-SCT HMT, comparison
      analysis of the prognostic values between the IPSS-R at the time of HMT (IPSS
      R@HMT) and at the time of SCT after HMT (IPSS-R@SCT) showed a significantly
      higher predictive power for overall survival (OS) of the latter. Alteration in
      IPSS-R risk occurred in 60%, while the patients with 'down-staged' IPSS-R@SCT
      showed better OS compared with those with 'unchanged' or 'up-staged' risk. On
      multivariate analysis in all 201 patients, IPSS-R@SCT, monosomal karyotype,
      treatment failure to pre-SCT treatment, and high hematopoietic cell
      transplantation-comorbidity index were independently associated with OS.
      Constructed using these factors, the MDS Transplantation Prognostic Scoring
      System (MTPSS) identified four risk groups with 4-year OS of 76.4% in low, 61.4%
      in intermediate-1 and 21.9% in intermediate-2 risk groups, whereas all in the
      high risk group died within 2 years after SCT (P<0.001). Our study emphasizes the
      need for further studies aiming to evaluate a transplantation prognostic model
      such as the MTPSS to make appropriate decisions for transplantation in MDS.

PMID- 27892955
TI  - Erratum: The histone deacetylase inhibiting drug Entinostat induces lipid
      accumulation in differentiated HepaRG cells.

PMID- 27892953
TI  - Thalamic miR-338-3p mediates auditory thalamocortical disruption and its late
      onset in models of 22q11.2 microdeletion.
AB  - Although 22q11.2 deletion syndrome (22q11DS) is associated with early-life
      behavioral abnormalities, affected individuals are also at high risk for the
      development of schizophrenia symptoms, including psychosis, later in life.
      Auditory thalamocortical (TC) projections recently emerged as a neural circuit
      that is specifically disrupted in mouse models of 22q11DS (hereafter referred to
      as 22q11DS mice), in which haploinsufficiency of the microRNA (miRNA)-processing
      factor-encoding gene Dgcr8 results in the elevation of the dopamine receptor Drd2
      in the auditory thalamus, an abnormal sensitivity of thalamocortical projections
      to antipsychotics, and an abnormal acoustic-startle response. Here we show that
      these auditory TC phenotypes have a delayed onset in 22q11DS mice and are
      associated with an age-dependent reduction of miR-338-3p, a miRNA that targets
      Drd2 and is enriched in the thalamus of both humans and mice. Replenishing
      depleted miR-338-3p in mature 22q11DS mice rescued the TC abnormalities, and
      deletion of Mir338 (which encodes miR-338-3p) or reduction of miR-338-3p
      expression mimicked the TC and behavioral deficits and eliminated the age
      dependence of these deficits. Therefore, miR-338-3p depletion is necessary and
      sufficient to disrupt auditory TC signaling in 22q11DS mice, and it may mediate
      the pathogenic mechanism of 22q11DS-related psychosis and control its late onset.

PMID- 27892954
TI  - A purified membrane protein from Akkermansia muciniphila or the pasteurized
      bacterium improves metabolism in obese and diabetic mice.
AB  - Obesity and type 2 diabetes are associated with low-grade inflammation and
      specific changes in gut microbiota composition. We previously demonstrated that
      administration of Akkermansia muciniphila to mice prevents the development of
      obesity and associated complications. However, the underlying mechanisms of this
      protective effect remain unclear. Moreover, the sensitivity of A. muciniphila to
      oxygen and the presence of animal-derived compounds in its growth medium
      currently limit the development of translational approaches for human medicine.
      We have addressed these issues here by showing that A. muciniphila retains its
      efficacy when grown on a synthetic medium compatible with human administration.
      Unexpectedly, we discovered that pasteurization of A. muciniphila enhanced its
      capacity to reduce fat mass development, insulin resistance and dyslipidemia in
      mice. These improvements were notably associated with a modulation of the host
      urinary metabolomics profile and intestinal energy absorption. We demonstrated
      that Amuc_1100, a specific protein isolated from the outer membrane of A.
      muciniphila, interacts with Toll-like receptor 2, is stable at temperatures used
      for pasteurization, improves the gut barrier and partly recapitulates the
      beneficial effects of the bacterium. Finally, we showed that administration of
      live or pasteurized A. muciniphila grown on the synthetic medium is safe in
      humans. These findings provide support for the use of different preparations of
      A. muciniphila as therapeutic options to target human obesity and associated
      disorders.

PMID- 27892957
TI  - Corrigendum: Lithium-ion-based solid electrolyte tuning of the carrier density in
      graphene.

PMID- 27892956
TI  - Phenology and Growth dynamics of Avicennia marina in the Central Red Sea.
AB  - The formation of nodes, stem elongation and the phenology of stunted Avicennia
      marina was examined in the Central Red Sea, where Avicennia marina is at the
      limit of its distribution range and submitted to extremely arid conditions with
      salinity above 38 psu and water temperature as high as 35 degrees  C. The annual
      node production was rather uniform among locations averaging 9.59 node y-1, which
      resulted in a plastocron interval, the interval in between production of two
      consecutive nodes along a stem, of 38 days. However, the internodal length varied
      significantly between locations, resulting in growth differences possibly
      reflecting the environmental conditions of locations. The reproductive cycle
      lasted for approximately 12 months, and was characterized by peak flowering and
      propagule development in November and January. These phenological observations
      provide a starting point for research and restoration programs on the ecology of
      mangroves in the Central Red Sea, while the plastochrone index reported here
      would allow calculations of the growth and production of the species from simple
      morphological measurements.

PMID- 27892958
TI  - A scored human protein-protein interaction network to catalyze genomic
      interpretation.
AB  - Genome-scale human protein-protein interaction networks are critical to
      understanding cell biology and interpreting genomic data, but challenging to
      produce experimentally. Through data integration and quality control, we provide
      a scored human protein-protein interaction network (InWeb_InBioMap, or InWeb_IM)
      with severalfold more interactions (>500,000) and better functional biological
      relevance than comparable resources. We illustrate that InWeb_InBioMap enables
      functional interpretation of >4,700 cancer genomes and genes involved in autism.

PMID- 27892959
TI  - novoBreak: local assembly for breakpoint detection in cancer genomes.
AB  - We present novoBreak, a genome-wide local assembly algorithm that discovers
      somatic and germline structural variation breakpoints in whole-genome sequencing
      data. novoBreak consistently outperformed existing algorithms on real cancer
      genome data and on synthetic tumors in the ICGC-TCGA DREAM 8.5 Somatic Mutation
      Calling Challenge primarily because it more effectively utilized reads spanning
      breakpoints. novoBreak also demonstrated great sensitivity in identifying short
      insertions and deletions.

PMID- 27892961
TI  - Host-derived extracellular RNA promotes adhesion of Streptococcus pneumoniae to
      endothelial and epithelial cells.
AB  - Streptococcus pneumoniae is the most frequent cause of community-acquired
      pneumonia. The infection process involves bacterial cell surface receptors, which
      interact with host extracellular matrix components to facilitate colonization and
      dissemination of bacteria. Here, we investigated the role of host-derived
      extracellular RNA (eRNA) in the process of pneumococcal alveolar epithelial cell
      infection. Our study demonstrates that eRNA dose-dependently increased S.
      pneumoniae invasion of alveolar epithelial cells. Extracellular enolase (Eno), a
      plasminogen (Plg) receptor, was identified as a novel eRNA-binding protein on S.
      pneumoniae surface, and six Eno eRNA-binding sites including a C-terminal 15
      amino acid motif containing lysine residue 434 were characterized. Although the
      substitution of lysine 434 for glycine (K434G) markedly diminished the binding of
      eRNA to Eno, the adherence to and internalization into alveolar epithelial cells
      of S. pneumoniae strain carrying the C-terminal lysine deletion and the mutation
      of internal Plg-binding motif were only marginally impaired. Accordingly, using a
      mass spectrometric approach, we identified seven novel eRNA-binding proteins in
      pneumococcal cell wall. Given the high number of eRNA-interacting proteins on
      pneumococci, treatment with RNase1 completely inhibited eRNA-mediated
      pneumococcal alveolar epithelial cell infection. Our data support further efforts
      to employ RNAse1 as an antimicrobial agent to combat pneumococcal infectious
      diseases.

PMID- 27892963
TI  - Stress Wave Propagation in Two-dimensional Buckyball Lattice.
AB  - Orderly arrayed granular crystals exhibit extraordinary capability to tune stress
      wave propagation. Granular system of higher dimension renders many more stress
      wave patterns, showing its great potential for physical and engineering
      applications. At nanoscale, one-dimensionally arranged buckyball (C60) system has
      shown the ability to support solitary wave. In this paper, stress wave behaviors
      of two-dimensional buckyball (C60) lattice are investigated based on square close
      packing and hexagonal close packing. We show that the square close packed system
      supports highly directional Nesterenko solitary waves along initially excited
      chains and hexagonal close packed system tends to distribute the impulse and
      dissipates impact exponentially. Results of numerical calculations based on a two
      dimensional nonlinear spring model are in a good agreement with the results of
      molecular dynamics simulations. This work enhances the understanding of wave
      properties and allows manipulations of nanoscale lattice and novel design of
      shock mitigation and nanoscale energy harvesting devices.

PMID- 27892962
TI  - Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by
      Electrospray Tandem Mass Spectrometry.
AB  - Mass spectrometric analysis of trace amounts of peptides may be problematic due
      to the insufficient ionization efficiency resulting in limited sensitivity. One
      of the possible ways to overcome this problem is the application of ionization
      enhancers. Herein we developed new ionization markers based on 2,4,6
      triphenylpyridinium and 2,4,6-trimethylpyridinium salts. Using of inexpensive and
      commercially available pyrylium salt allows selective derivatization of primary
      amino groups, especially those sterically unhindered, such as epsilon-amino group
      of lysine. The 2,4,6-triphenylpyridinium modified peptides generate in MS/MS
      experiments an abundant protonated 2,4,6-triphenylpyridinium ion. This fragment
      is a promising reporter ion for the multiple reactions monitoring (MRM) analysis.
      In addition, the fixed positive charge of the pyridinium group enhances the
      ionization efficiency. Other advantages of the proposed ionization enhancers are
      the simplicity of derivatization of peptides and the possibility of convenient
      incorporation of isotopic labels into derivatized peptides.

PMID- 27892960
TI  - New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium
      Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and
      Unconventional Cytokine Profiles.
AB  - New strategies are needed to develop better tools to control TB, including
      identification of novel antigens for vaccination. Such Mtb antigens must be
      expressed during Mtb infection in the major target organ, the lung, and must be
      capable of eliciting human immune responses. Using genome-wide transcriptomics of
      Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo
      expressed Mtb) antigens expressed in the lung. Quantitative expression analysis
      of 2,068 Mtb genes from the predicted first operons identified the most
      upregulated IVE-TB genes during in-vivo pulmonary infection. By further analysing
      high-level conservation among whole-genome sequenced Mtb-complex strains (n =
      219) and algorithms predicting HLA-class-Ia and II presented epitopes, we
      selected the most promising IVE-TB candidate antigens. Several of these were
      recognized by T-cells from in-vitro Mtb-PPD and ESAT6/CFP10-positive donors by
      proliferation and multi-cytokine production. This was validated in an independent
      cohort of latently Mtb-infected individuals. Significant T-cell responses were
      observed in the absence of IFN-gamma-production. Collectively, the results
      underscore the power of our novel antigen discovery approach in identifying Mtb
      antigens, including those that induce unconventional T-cell responses, which may
      provide important novel tools for TB vaccination and biomarker profiling. Our
      generic approach is applicable to other infectious diseases.

PMID- 27892964
TI  - Temporally-coherent terawatt attosecond XFEL synchronized with a few cycle laser.
AB  - Attosecond metrology using laser-based high-order harmonics has been
      significantly advanced and applied to various studies of electron dynamics in
      atoms, molecules and solids. Laser-based high-order harmonics have a limitation
      of low power and photon energies. There is, however, a great demand for even
      higher power and photon energy. Here, we propose a scheme for a terawatt
      attosecond (TW-as) X-ray pulse in X-ray free-electron laser controlled by a few
      cycle IR pulse, where one dominant current spike in an electron bunch is used
      repeatedly to amplify a seeded radiation to a terawatt level. This scheme is
      relatively simple, compact, straightforward, and also produces a temporally and
      spectrally clean pulse. The viability of this scheme is demonstrated in
      simulations using Pohang accelerator laboratory (PAL)-XFEL beam parameters.

PMID- 27892965
TI  - Diabetes Mellitus and Risk of Colorectal Cancer Mortality inJapan: the Japan
      Collaborative Cohort Study
AB  - Objective: Our aim was to estimate whether diabetes mellitus (DM) may be
      associated with an increased risk ofcolorectal cancer (CRC) mortality in Japan.
      Methods: The Japan Collaborative Cohort (JACC) Study is a nationwideprospective
      study, initiated in 1988, which involves 110,585 subjects (age range: from 40 to
      79 years; 46,395 males and64,190 females). Our present analysis population
      comprised 96,081 (40,510 men and 55,571 women) who provideddetails on DM history.
      The questionnaire also included age, sex, weight, height, family history of CRC,
      smoking,drinking and exercise habits, and education. Cox proportional-hazard
      regression was used to estimate the hazard ratio(HR). We used SPSS 21 software to
      analyze all data. Results: Among the participants with DM, we followed up
      for71,174 person-years and 640. deaths from CRC were confirmed; and, among the
      non-diabetic participants, 785 CRCdeaths were identified during 1,499,324 person
      years. After adjusting for multivariate confounding factors, such asage, sex,
      body mass index (BMI), family history of colorectal cancer, smoking habit,
      drinking habit, physical activity(sports and walking) and education, DM was
      associated with an increased risk of CRC death (HR 1.4, 95% confidenceinterval
      [CI] 1.0-2.0). Diabetic women, but not diabetic men, experienced increased
      mortality from CRC (HR 1.7, 95%CI 1.0-3.0). Conclusion: The risk of CRC mortality
      is significantly increased in both sexes and women with diabetes,but no
      significant increase was seen for diabetic men among Japanese.

PMID- 27892968
TI  - Reactions at the nanoscale: general discussion.

PMID- 27892970
TI  - From single cells to single molecules: general discussion.

PMID- 27892974
TI  - Dimalononitrile-containing probe based on aggregation-enhanced emission features
      for the multi-mode fluorescence detection of volatile amines.
AB  - A novel multi-mode probe consisting of a hexaphenyl-1,3-butadiene derivative,
      2,2'-((((1Z,3Z)-1,2,3,4-tetraphenylbuta-1,3-diene-1,4-diyl)bis(4,1
      phenylene))bis(methanylylidene))dimalononitrile (ZZ-HPB-CN), with typical
      aggregation-enhanced emission (AEE) features was easily prepared for the highly
      sensitive and rapid detection of amine vapors. The ZZ-HPB-CN sensor, which was
      prepared by simply depositing ZZ-HPB-CN on filter paper, could detect low
      concentration vapors of volatile amines using fluorescence, ultraviolet and naked
      eye detection. The limit of detection of the sensor was as low as 1 ppb for the
      fluorescence detection. The color change of the sensor caused by 1-10 ppm amine
      vapors could be observed under UV light or with the naked eye. The high
      sensitivity, quick response and easy operation of the probe give it great
      potential for real-life applications.

PMID- 27892971
TI  - Electrochemistry of single nanoparticles: general discussion.

PMID- 27892966
TI  - Effect of sex, age and genetics on crossover interference in cattle.
AB  - Crossovers generated by homologous recombination ensure proper chromosome
      segregation during meiosis. Crossover interference results in chiasmata being
      more evenly distributed along chromosomes, but the mechanism underlying crossover
      interference remains elusive. Based on large pedigrees of Holstein and Jersey
      cattle with genotype data, we extracted three-generation families, including
      147,327 male and 71,687 female meioses in Holstein, and 108,163 male and 37,008
      female meioses in Jersey, respectively. We identified crossovers in these meioses
      and fitted the Housworth-Stahl "interference-escape" model to study crossover
      interference patterns in the cattle genome. Our result reveals that the degree of
      crossover interference is stronger in females than in males. We found evidence
      for inter-chromosomal variation in the level of crossover interference, with
      smaller chromosomes exhibiting stronger interference. In addition, crossover
      interference levels decreased with maternal age. Finally, sex-specific GWAS
      analyses identified one locus near the NEK9 gene on chromosome 10 to have a
      significant effect on crossover interference levels. This locus has been
      previously associated with recombination rate in cattle. Collectively, this large
      scale analysis provided a comprehensive description of crossover interference
      across chromosome, sex and age groups, identified associated candidate genes, and
      produced useful insights into the mechanism of crossover interference.

PMID- 27892975
TI  - Nanopores: general discussion.

PMID- 27892976
TI  - Validation of a Method for Estimation of Facial Age by Plastic Surgeons.
AB  - Importance: Within cosmetic facial plastic surgery, there is considerable
      difficulty in producing high-quality scientific publications because of the lack
      of scientific tools that serve to transform sensations, such as more beautiful or
      rejuvenated, into numbers capable of being used in statistical analysis.
      Objective: To validate an objective evaluation method that can be used to define
      the perception of facial age in scientific studies. Design, Setting, and
      Participants: This is a cross-sectional, observational study of evaluation by
      plastic surgeons of 70 photographs of patients from a private care hospital
      performed from March 1, 2015, through April 30, 2016. When evaluating the
      photographs, 7 plastic surgeons wrote down the perceived age of each patient. The
      photographs of each patient were randomly presented twice to each evaluator
      (photograph 1 and photograph 2) and analyzed singly using a trimmed mean. Three
      evaluators were randomly chosen for further statistical analysis in an attempt to
      make the assessment technique more practical. Exposures: Usual aging process.
      Main Outcomes and Measures: Estimated mean age and chronological age. Results:
      Photographs of 70 patients were evaluated (mean [SD] age, 41.5 [13.8] years; 48
      women [68.6%]; and mean [SD] body mass index, 22.5 [2.7]). No significant
      differences were observed between photographs 1 and 2 for any of the evaluators.
      A significant difference in the mean ages was not observed when comparing
      evaluators. For photograph 1 (evaluated by only 3 evaluators), the difference was
      0.16 years (P = .52). For photograph 2, the difference was 0.05 years (P = .86).
      The difference between the mean perceived age for the 3 evaluators and the
      chronological age was only 0.8 years (<10 months). Conclusions and Relevance: The
      intraevaluator and interevaluator agreement suggests that 3 plastic surgeons can
      estimate the age of a person with a margin of error of 10 months by analyzing a
      photograph. This article is important to facial plastic surgeons because it
      reveals how the results of rejuvenation procedures can be assessed. Level of
      Evidence: NA.

PMID- 27892977
TI  - Societal Value of Surgery for Facial Reanimation.
AB  - Importance: Patients with facial paralysis are perceived negatively by society in
      a number of domains. Society's perception of the health utility of varying
      degrees of facial paralysis and the value society places on reconstructive
      surgery for facial reanimation need to be quantified. Objective: To measure
      health state utility of varying degrees of facial paralysis, willingness to pay
      (WTP) for a repair, and the subsequent value of facial reanimation surgery as
      perceived by society. Design, Setting, and Participants: This prospective
      observational study conducted in an academic tertiary referral center evaluated a
      group of 348 casual observers who viewed images of faces with unilateral facial
      paralysis of 3 severity levels (low, medium, and high) categorized by House
      Brackmann grade. Structural equation modeling was performed to understand
      associations among health utility metrics, WTP, and facial perception domains.
      Data were collected from July 16 to September 26, 2015. Main Outcomes and
      Measures: Observer-rated (1) quality of life (QOL) using established health
      utility metrics (standard gamble, time trade-off, and a visual analog scale) and
      (2) their WTP for surgical repair. Results: Among the 348 observers (248 women
      [71.3%]; 100 men [28.7%]; mean [SD] age, 29.3 [11.6] years), mixed-effects linear
      regression showed that WTP increased nonlinearly with increasing severity of
      paralysis. Participants were willing to pay $3487 (95% CI, $2362-$4961) to repair
      low-grade paralysis, $8571 (95% CI, $6401-$11 234) for medium-grade paralysis,
      and $20 431 (95% CI, $16 273-$25 317) for high-grade paralysis. The dominant
      factor affecting the participants' WTP was perceived QOL. Modeling showed that
      perceived QOL decreased with paralysis severity (regression coefficient, -0.004;
      95% CI, -0.005 to -0.004; P < .001) and increased with attractiveness (regression
      coefficient, 0.002; 95% CI, 0.002 to 0.003; P < .001). Mean (SD) health utility
      scores calculated by the standard gamble metric for low- and high-grade paralysis
      were 0.98 (0.09) and 0.77 (0.25), respectively. Time trade-off and visual analog
      scale measures were highly correlated. We calculated mean (SD) WTP per quality
      adjusted life-year, which ranged from $10 167 ($14 565) to $17 008 ($38 288) for
      low- to high-grade paralysis, respectively. Conclusions and Relevance: Society
      perceives the repair of facial paralysis to be a high-value intervention.
      Societal WTP increases and perceived health state utility decreases with
      increasing House-Brackmann grade. This study demonstrates the usefulness of WTP
      as an objective measure to inform dimensions of disease severity and signal the
      value society places on proper facial function. Level of Evidence: NA.

PMID- 27892979
TI  - The Need for Ergonomics Education in Dermatology and Dermatologic Surgery: Sit Up
      Straight, Stand Up Tall, and Carry a Sharp Scalpel.

PMID- 27892980
TI  - Ocular Toxicity of Mitogen-Activated Protein Kinase Inhibitors.

PMID- 27892981
TI  - Rituximab in Treatment-Refractory Myasthenia Gravis.

PMID- 27892978
TI  - Estimating Survival in Patients With Lung Cancer and Brain Metastases: An Update
      of the Graded Prognostic Assessment for Lung Cancer Using Molecular Markers (Lung
      molGPA).
AB  - Importance: Lung cancer is the leading cause of cancer-related mortality in the
      United States and worldwide. As systemic therapies improve, patients with lung
      cancer live longer and thus are at increased risk for brain metastases.
      Understanding how prognosis varies across this heterogeneous patient population
      is essential to individualize care and design future clinical trials. Objective:
      To update the current Diagnosis-Specific Graded Prognostic Assessment (DS-GPA)
      for patients with non-small-cell lung cancer (NSCLC) and brain metastases. The DS
      GPA is based on data from patients diagnosed between 1985 and 2005, and we set
      out to update it by incorporating more recently reported gene and molecular
      alteration data for patients with NSCLC and brain metastases. This new index is
      called the Lung-molGPA. Design, Setting, and Participants: This is a multi
      institutional retrospective database analysis of 2186 patients diagnosed between
      2006 and 2014 with NSCLC and newly diagnosed brain metastases. The multivariable
      analyses took place between December 2015 and May 2016, and all prognostic
      factors were weighted for significance by hazard ratios. Significant factors were
      included in the updated Lung-molGPA prognostic index. Main Outcomes and Measures:
      The main outcome was survival. Multiple Cox regression was used to select and
      weight prognostic factors in proportion to their hazard ratios. Log rank tests
      were used to compare adjacent classes and to compare overall survival for
      adenocarcinoma vs nonadenocarcinoma groups. Results: The original DS-GPA was
      based on 4 factors found in 1833 patients with NSCLC and brain metastases
      diagnosed between 1985 and 2005: patient age, Karnofsky Performance Status,
      extracranial metastases, and number of brain metastases. The patients studied for
      the creation of the DS-GPA had a median survival of 7 months from the time of
      initial treatment of brain metastases. To design the updated Lung-molGPA, we
      analyzed data from 2186 patients from 2006 through 2014 with NSCLC and newly
      diagnosed brain metastases (1521 adenocarcinoma and 665 nonadenocarcinoma).
      Significant prognostic factors included the original 4 factors used in the DS-GPA
      index plus 2 new factors: EGFR and ALK alterations in patients with
      adenocarcinoma (mutation status was not routinely tested for nonadenocarcinoma).
      The overall median survival for the cohort in the present study was 12 months,
      and those with NSCLC-adenocarcinoma and Lung-molGPA scores of 3.5 to 4.0 had a
      median survival of nearly 4 years. Conclusions and Relevance: In recent years,
      patient survival and physicians' ability to predict survival in NSCLC with brain
      metastases has improved significantly. The updated Lung-molGPA incorporating gene
      alteration data into the DS-GPA is a user-friendly tool that may facilitate
      clinical decision making and appropriate stratification of future clinical
      trials.

PMID- 27892982
TI  - Vision Loss in a Teenage Girl With Postconcussion Syndrome.

PMID- 27892983
TI  - Association of Mutations in TBK1 With Sporadic and Familial Amyotrophic Lateral
      Sclerosis and Frontotemporal Dementia.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related
      neurodegenerative syndromes that occur sporadically or have been associated with
      mostly dominant inheritance of mutations in more than 30 genes. A critical issue
      is whether all reported mutations are disease causing or are coincidental
      findings. In this review we analyze the pathogenicity of nonsynonymous variants
      in the newly discovered gene encoding TANK-binding kinase 1 (TBK1). The available
      data suggest that mutations in TBK1 that cause a 50% reduction of TBK1 protein
      levels are pathogenic. In most cases, the almost complete loss of expression of
      the mutated TBK1 allele is due to loss-of-function mutations creating a premature
      termination codon and the degradation of the mutated messenger RNA by nonsense
      mediated messenger RNA decay. In addition, TBK1 protein levels reduced by 50%
      have been proven for specific in-frame deletions of 1 or several amino acids,
      probably due to increased degradation of the mutated protein. Evaluation of many
      of the TBK1 missense mutations found in patients with ALS or FTD is prevented by
      missing data demonstrating cosegregation of the variants and incomplete knowledge
      about the TBK1 functions relevant for neurodegeneration. These findings suggest
      that haploinsufficiency of TBK1 is causative for ALS and FTD regardless of the
      type of mutation. Evaluation of TBK1 variants that do not cause
      haploinsufficiency is not possible without data demonstrating cosegregation.

PMID- 27892985
TI  - Adoption of Pathologic Complete Response as a Surrogate End Point in Neoadjuvant
      Trials in HER2-Positive Breast Cancer Still an Open Question-Reply.

PMID- 27892984
TI  - Anatomical Distributions of Basal Cell Carcinoma and Squamous Cell Carcinoma in a
      Population-Based Study in Queensland, Australia.
AB  - Importance: Keratinocyte cancers (KCs), including basal cell carcinoma (BCC) and
      squamous cell carcinoma (SCC), are the most common cancers among fair-skinned
      populations worldwide. Although studies have indicated that the anatomical
      distribution of BCC and SCC differ, few have compared them directly in well
      defined population samples. Objectives: To describe and compare the anatomical
      distribution of BCC and SCC in a population-based sample in Queensland,
      Australia. Design, Setting, and Participants: This study was nested within the
      population-based QSkin Sun and Health Study in Queensland, Australia. Of 37 103
      study participants linked to national medical insurance records, 3398 diagnosed
      with KCs from September 1, 2010, to September 30, 2012, were identified, and
      information about their KCs was extracted from pathology reports. Data were
      analyzed from January 1, 2013, to March 30, 2016. Main Outcomes and Measures: The
      relative tumor densities (RTDs) on defined body sites, calculated by dividing the
      proportion of tumors occurring at a specified site by the proportion of skin area
      of that site. Results: A total of 5150 KCs with complete data were identified in
      2374 study participants (1339 men [56.4%] and 1035 women [43.6%]; mean [SD] age,
      59.7 [7.4] years). Of these, 3846 KCs (74.7%) were BCCs. Most BCCs were on the
      head and/or neck (1547 [40.2%]) and the trunk (1305 [33.9%]); most SCCs were on
      the head and/or neck (435 [33.4%]) and upper limbs (455 [34.9%]). The greatest
      differences in RTDs between BCC and SCC were on the hand (BCC:SCC ratio, 1:14)
      and the back and/or buttocks (BCC:SCC ratio, 8:1). Relative tumor densities of
      KCs were higher on the scalp and ear in men compared with women, and on the upper
      arm in women compared with men. The pattern of RTDs did not differ with age for
      BCC. Compared with younger adults (40-54 years), the RTDs in older adults (55-69
      years) were 2-fold higher for SCC on the scalp (0.38 [95% CI, 0.00-0.81] vs 1.07
      [95% CI, 0.75-1.38]) and the back and/or buttocks (0.05 [95% CI, 0.00-0.12] vs
      0.12 [95% CI, 0.07-0.16]). Conclusions and Relevance: The high RTDs on sun
      exposed body sites for BCC and SCC are in keeping with sun exposure as the
      primary etiologic factor for both tumors. However, for BCC, the low RTD on the
      hand and high RTDs on less sun-exposed sites suggest a complex association
      between sun exposure and occurrence of BCC. Knowledge about the anatomical
      distribution of BCC and SCC may provide insight into their diagnoses and causes.

PMID- 27892986
TI  - New Yellow Plaques in a Patient Taking Pembrolizumab.

PMID- 27892988
TI  - Association of Molecular Marker Status With Graded Prognostic Assessment of Lung
      Cancer With Brain Metastases.

PMID- 27892987
TI  - Sweet-Like Eruption Associated With Obinutuzumab Therapy for Chronic Lymphocytic
      Leukemia.

PMID- 27892989
TI  - Patient-Acquired Photographs for the Management of Postoperative Concerns.

PMID- 27892990
TI  - Zika Virus-What the Otolaryngologist Should Know: A Review.
AB  - Importance: Initially discovered in 1947, Zika virus infection received little
      notoriety as a tropical disease until 2015 when an outbreak of microcephaly cases
      was reported in Brazil. Zika is a single-stranded RNA arbovirus of the
      Flaviviridae family. The primary source of infection in humans stems from Aedes
      aegypti mosquito bites but can also occur through sexual, blood, and perinatal
      transmission. With expectations that 3 to 4 million people across the Americas
      will be infected over the next year, the World Health Organization has declared
      this event a Public Health Emergency of International Concern. Observations:
      Although acute Zika virus infection is typically mild and self-limited,
      researchers have demonstrated serious neurologic complications associated with it
      such as microcephaly and Guillain-Barre syndrome. Otolaryngologists should be
      aware of head and neck manifestations which include conjunctivitis, retro-orbital
      pain, cephalgia, and odynophagia. The Centers for Disease Control and Prevention
      have developed specific molecular and serologic testing protocols and algorithms
      for follow-up care of suspected cases. Currently, the mainstay of management is
      conservative care while researchers attempt to develop a vaccine. Strategies to
      contain the Zika virus include vector control, travel restriction for women who
      are pregnant or trying to become pregnant, and avoidance of mosquito bites in
      endemic regions of the world. Conclusions and Revelance: The future outlook
      regarding the current Zika virus outbreak in the Americas remains uncertain. What
      is certain is our need to promptly and efficiently address research gaps in our
      understanding of clinical outcomes from infection and environmental factors that
      influence emergence meanwhile improving diagnostic, therapeutic, and preventive
      measures against the disease.

PMID- 27892992
TI  - Overall Survival in Cancer Drug Trials as a New Surrogate End Point for Overall
      Survival in the Real World.

PMID- 27892993
TI  - Third Nerve Palsies-Less Frequent but Just as Concerning.

PMID- 27892991
TI  - Surveillance Mammography in Older Patients With Breast Cancer-Can We Ever Stop?:
      A Review.
AB  - Importance: Approximately 4% to 5% of breast cancer survivors will develop a new
      ipsilateral or contralateral cancer (in-breast event) over the 5 years following
      diagnosis, and annual surveillance mammography is recommended for those with
      residual breast tissue. The risk for such in-breast events persists over time,
      though increasing age at cancer diagnosis and treatment with hormonal therapy are
      associated with lower risk, and most older survivors of breast cancer will
      ultimately die from nonbreast cancer-related causes. Specific guidelines for
      surveillance strategies in older patients are limited. Prospective data on the
      benefits and harms of surveillance mammography in this population are lacking,
      and most of the evidence is derived from observational, retrospective data, often
      in the general population. Observations: We review the current recommendations
      for breast cancer screening and surveillance for older patients, the current
      evidence for ipsilateral and contralateral breast cancer risks in older survivors
      of breast cancer, and suggested approaches for discussions about surveillance
      mammography with older patients. We recommend individualized decision making for
      surveillance breast imaging in older survivors of breast cancer, with
      consideration of the following strategy for women 70 years or older: 1-time
      imaging 6 to 12 months after completion of local therapy followed by annual or
      biennial surveillance mammography for healthy women and cessation of mammography
      in patients whose life expectancy is less than 5 years to 10 years, regardless of
      age. Decisions on mammographic surveillance should also incorporate whether
      hormonal therapy is being administered, whether a patient's anticipated life
      expectancy is extraordinary, and whether a patient's individual risk for in
      breast events is higher (or lower) than average risk for breast cancer survivors.
      Conclusions and Relevance: We propose reframing discussions around surveillance
      mammography in older breast cancer survivors and to consider cessation while
      taking into account life expectancy, the estimated risk for subsequent in-breast
      events, and patient preferences.

PMID- 27892994
TI  - Adoption of Pathologic Complete Response as a Surrogate End Point in Neoadjuvant
      Trials in HER2-Positive Breast Cancer Still an Open Question.

PMID- 27892995
TI  - Laryngeal Mass in an Infant.

PMID- 27892996
TI  - Technique Standards for Skin Lesion Imaging: A Delphi Consensus Statement.
AB  - Importance: Variability in the metrics for image acquisition at the total body,
      regional, close-up, and dermoscopic levels impacts the quality and
      generalizability of skin images. Consensus guidelines are indicated to achieve
      universal imaging standards in dermatology. Objective: To achieve consensus among
      members of the International Skin Imaging Collaboration (ISIC) on standards for
      image acquisition metrics using a hybrid Delphi method. Evidence Review: Delphi
      study with 5 rounds of ratings and revisions until relative consensus was
      achieved. The initial set of statements was developed by a core group (CG) on the
      basis of a literature review and clinical experience followed by 2 rounds of
      rating and revisions. The consensus process was validated by an extended group
      (EG) of ISIC members through 2 rounds of scoring and revisions. In all rounds,
      respondents rated the draft recommendations on a 1 (strongly agree) to 5
      (strongly disagree) scale, explained ratings of less than 5, and optionally
      provided comments. At any stage, a recommendation was retained if both mean and
      median rating was 4 or higher. Results: The initial set of 45 items (round 1) was
      expanded by the CG to 56 variants in round 2, subsequently reduced to 42 items
      scored by the EG in round 3, yielding an EG set of 33 recommendations (rounds 4
      and 5): general recommendation (1 guideline), lighting (5), background color (3),
      field of view (3), image orientation (8), focus/depth of field (3), resolution
      (4), scale (3), color calibration (2), and image storage (1). Conclusions and
      Relevance: This iterative process of ratings and comments yielded a strong
      consensus on standards for skin imaging in dermatology practice. Adoption of
      these methods for image standardization is likely to improve clinical practice,
      information exchange, electronic health record documentation, harmonization of
      clinical studies and database development, and clinical decision support.
      Feasibility and validity testing under real-world clinical conditions is
      indicated.

PMID- 27892997
TI  - Otolaryngologist-Beware of Zika.

PMID- 27892999
TI  - Omitted Author Name in Print Article.

PMID- 27892998
TI  - Overall Survival Following Neoadjuvant Chemotherapy vs Primary Cytoreductive
      Surgery in Women With Epithelial Ovarian Cancer: Analysis of the National Cancer
      Database.
AB  - Importance: Uncertainty remains about the relative benefits of primary
      cytoreductive surgery (PCS) vs neoadjuvant chemotherapy (NACT) for advanced-stage
      epithelial ovarian cancer (EOC). Objective: To compare overall survival of PCS vs
      NACT in a large national population of women with advanced-stage EOC. Design,
      Setting, and Participants: Retrospective cohort study of women with stage IIIC
      and IV EOC diagnosed between 2003 and 2011 treated at hospitals across the United
      States reporting to the National Cancer Data Base. We focused on patients 70
      years or younger with a Charlson comorbidity index of 0 who were likely
      candidates for either treatment. Exposures: Initial treatment approach of PCS vs
      NACT, examined using an intent-to-treat analysis. Main Outcomes and Measures:
      Overall survival, defined as months from cancer diagnosis to death or date of the
      last contact. We used propensity score matching to compare similar women who
      underwent PCS and NACT. The association of treatment approach with overall
      survival was assessed using the Kaplan-Meier method and the log-rank test. We
      assessed whether the findings were influenced by differences in the prevalence of
      an unobserved confounder, such as limited performance status (Eastern Cooperative
      Oncology Group 1-2), preoperative disease burden, and BRCA status. Results: Among
      22 962 patients (mean [SD] age, 56.12 [9.38] years), 19 836 (86.4%) received PCS
      and 3126 (13.6%) underwent NACT. We matched 2935 patients treated with NACT with
      similar patients who received PCS. The median follow-up was 56.5 (95% CI, 54.5
      59.2) months in the PCS group and 56.3 (95% CI, 54.5-59.8) months in the NACT
      group in the propensity-matched cohort. Among propensity score-matched groups,
      the median overall survival was 37.3 (95% CI, 35.2-38.7) months in the PCS group
      and 32.1 (95% CI, 30.8-34.1) months in the NACT group (P < .001). However, if the
      NACT group had a higher proportion of women with performance statuses of 1 to 2
      compared with those who underwent PCS (60% vs 50%), the association of PCS and
      improved survival would not be statistically significant. Conclusions and
      Relevance: Primary cytoreductive surgery was associated with improved survival
      compared with NACT in otherwise healthy women with advanced-stage epithelial
      ovarian cancer aged 70 years or younger. The lower survival in women who received
      NACT could be explained by a higher prevalence of limited performance status in
      women undergoing NACT.

PMID- 27893000
TI  - Association Between Benzodiazepine Receptor Agonists and Snoring Among Women in
      the Nurses' Health Study.
AB  - Importance: Snoring is highly prevalent among adults. The use of benzodiazepine
      receptor agonists is also common, with higher prevalence of use with more
      advanced age. Benzodiazepine receptor agonists cause muscle relaxation, which may
      affect muscle tone and airway dynamics and thereby increase snoring. Previous
      studies examining the association between use of benzodiazepine receptor agonists
      and snoring were underpowered to detect clinically meaningful differences or did
      not report the magnitude of association. Objective: To investigate the
      association between use of benzodiazepine receptor agonists and snoring in women.
      Design, Setting, and Participants: Women aged 62 to 86 years provided information
      on snoring and covariates of interest in the 2008 survey of the Nurses' Health
      Study, a cross-sectional cohort study of female registered nurses in the United
      States. Potential effect modification of the association between use of
      benzodiazepine receptor agonists and snoring by age, body mass index, waist
      circumference, smoking, alcohol consumption, and physical activity was explored.
      Logistic regression was used to adjust for potential confounders. Data analysis
      was conducted from November 2015 to March 2016. Main Outcomes and Measures: Self
      reported habitual snoring, defined as a few nights a week or more. Results: Of 52
      504 participants (mean [SD] age, 72.4 [6.7] years), 14 831 (28.2%) reported
      habitual snoring. There was a slightly higher prevalence of benzodiazepine
      receptor agonist use among habitual snorers (11.4%) compared with nonhabitual
      snorers (10.6%) (absolute difference, 0.8%; 95% CI, 0.2%-1.4%). After
      multivariable adjustment, use of benzodiazepine receptor agonists was not
      associated with snoring (odds ratio, 1.01; 95% CI, 0.95-1.07) compared with women
      who did not use benzodiazepine receptor agonists. Although there was no
      significant interaction with smoking, there were higher odds of snoring with use
      of benzodiazepine receptor agonists among current smokers (odds ratio, 1.34; 95%
      CI, 1.04-1.73). Conclusions and Relevance: Use of benzodiazepine receptor
      agonists is not associated with odds of snoring in middle-aged and elderly women.

PMID- 27893001
TI  - Association of Improved Locoregional Control With Prolonged Survival in Early
      Stage Extranodal Nasal-Type Natural Killer/T-Cell Lymphoma.
AB  - Importance: The long-term survival benefit for radiotherapy (RT) in early-stage
      extranodal natural killer/T-cell lymphoma (NKTCL) is not known, and it is unclear
      whether improved locoregional control (LRC) translates into a survival benefit.
      Objective: To investigate the dose-dependent effect and potential survival
      benefits of RT on the basis of LRC improvements. Design, Setting, and
      Participants: Review of clinical data of patients with early-stage NKTCL at 10
      institutions in China between 2000 and 2014. Radiotherapy dose as a continuous
      variable was entered into the Cox regression model by using penalized spline
      regression to allow for a nonlinear relationship between RT dose and events.
      Regression analysis was used to assess whether a linear correlation exists
      between LRC and progression-free survival (PFS) or overall survival (OS).
      Patients received chemotherapy (CT) alone, RT alone, or a combination.
      Chemotherapy alone was defined as 0 Gy. Main Outcomes and Measures: The
      association between LRC and OS or PFS. Results: A total of 1332 patients (923
      [69%] male; median age, 43 years [range, 2-87 years]) were reviewed. For patients
      treated with RT, median dose was 50 Gy (range, 10-70 Gy); 996 (86%) received at
      least 50 Gy, and 164 (14%) received 10 to 49 Gy. The risk of locoregional
      recurrence, disease progression, and mortality decreased sharply until 50 to 52
      Gy. For patients receiving RT, high-dose RT (>=50 Gy) was associated with
      significantly better 5-year LRC (85% vs 73%; P < .001), PFS (61% vs 50%; P =
      .004), and OS (70% vs 58%; P = .04) than low-dose RT (<50 Gy). Improved LRC with
      high-dose RT was independent of the RT/CT sequence or initial response to CT.
      Radiotherapy yielded a dose-dependent effect on LRC (range, 41%-87%), PFS (18%
      63%), and OS (33%-71%). Dose-response regression analysis revealed a linear
      correlation between 5-year LRC and 5-year PFS (correlation coefficient, r =
      0.994, P < .001; determination coefficient, R2 = 0.988) or 5-year OS (r = 0.985,
      P = .002; R2 = 0.97), which was externally validated using published data.
      Conclusions and Relevance: The optimal dose was 50 Gy for patients with early
      stage disease. The improved LRC was associated with prolonged survival. These
      findings emphasize the importance of RT in optimizing first-line therapy, and
      provide evidence for making treatment decisions and designing clinical trials.

PMID- 27893002
TI  - Incidence and Etiologies of Acquired Third Nerve Palsy Using a Population-Based
      Method.
AB  - Importance: Among cranial nerve palsies, a third nerve palsy is important because
      a subset is caused by life-threatening aneurysms. However, there is significant
      disagreement regarding its incidence and the reported etiologies. Objective: To
      determine the incidence and etiologies of acquired third nerve palsy using a
      population-based method. Design, Setting, and Participants: All newly diagnosed
      cases of acquired third nerve palsy from January 1, 1978, through December 31,
      2014, in Olmsted County, Minnesota, were identified using the Rochester
      Epidemiology Project, a record-linkage system of medical records for all patient
      physician encounters among Olmsted County residents. All medical records were
      reviewed to confirm a diagnosis of acquired third nerve palsy and determine the
      etiologies, presenting signs, and symptoms. Incidence rates were adjusted to the
      age and sex distribution of the 2010 US white population. Main Outcomes and
      Measures: Incidence and etiologies of acquired third nerve palsies. The secondary
      outcome was incidence of pupil involvement in acquired third nerve palsies.
      Results: We identified 145 newly diagnosed cases of acquired third nerve palsy in
      Olmsted County, Minnesota, over the 37-year period. The age- and sex-adjusted
      annual incidence of acquired third nerve palsy was 4.0 per 100 000 (95% CI, 3.3
      4.7 per 100 000). The annual incidence in patients older than 60 was greater than
      patients younger than 60 (12.5 vs 1.7 per 100 000; difference, 10.8 per 100 000;
      95% CI, 4.7-16.9; P < .001). The most common causes of acquired third nerve palsy
      were presumed microvascular (42%), trauma (12%), compression from neoplasm (11%),
      postneurosurgery (10%), and compression from aneurysm (6%). Ten patients (17%)
      with microvascular third nerve palsies had pupil involvement, while pupil
      involvement was seen in 16 patients (64%) with compressive third nerve palsies.
      Conclusions and Relevance: This population-based cohort demonstrates a higher
      incidence of presumed microvascular third nerve palsies and a lower incidence of
      aneurysmal compression than previously reported in non-population-based studies.
      While compressive lesions had a higher likelihood of pupil involvement, pupil
      involvement did not exclude microvascular third nerve palsy and lack of pupil
      involvement did not rule out compressive third nerve palsy.

PMID- 27893003
TI  - Navigation Guidance During Free Flap Mandibular Reconstruction: A Cadaveric
      Trial.
AB  - Importance: Segmental mandibulectomy for tumors that distort the buccal surface
      of the mandible present a reconstructive challenge. Objective: To determine
      whether mandible alignment after navigation-guided mandible reconstruction is
      better than alignment after non-template-assisted freehand reconstruction and as
      good as template-assisted reconstruction in a cadaveric trial. Design, Setting,
      and Participants: A cadaveric trial using 10 specimens was conducted at a
      tertiary academic center. Fiducials were created on the ramus to compare
      alignment with each intervention. Segmental mandibulectomy was performed on each
      cadaver. Each cadaver underwent navigation-guided reconstruction, template
      assisted reconstruction using a manually shaped plate, and non-template-assisted
      freehand reconstruction with plate contouring performed after mandibulectomy. The
      study was conducted from October 1, 2015, to January 1, 2016; data analysis was
      performed from February 1, 2016, to March 1, 2016. Interventions: Segmental
      mandibulectomy, navigation-guided reconstruction, template-assisted
      reconstruction using a manually shaped plate, and non-template-assisted freehand
      reconstruction. Main Outcomes and Measures: Ramus fiducial coordinates were
      recorded at baseline and after each intervention. Mandible dimensions were
      measured using cephalometric landmarks. Postintervention and baseline differences
      in ramus and mandible position were calculated. Results: Ramus alignment was not
      significantly different between navigation-guided and template-assisted
      reconstruction, differing by 0.54 mm (98.3% CI, -0.38 to 1.47 mm). Non-template
      assisted freehand reconstruction was associated with a 3.14-mm difference in
      alignment compared with template-assisted reconstruction (98.3% CI, 1.09 to 5.19
      mm). Navigation-guided alignment resulted in a 3.69-mm improvement in alignment
      compared with non-template-assisted freehand reconstruction (98.3% CI, 1.79 to
      5.58 mm). There was some improvement in the gonion-gonion and lingula mandibulae
      lingula mandibulae (Lm-Lm) alignment for navigation-assisted compared with non
      template-assisted freehand reconstruction by 1.97 mm (98.3% CI, -0.65 to 4.58 mm)
      and 1.39 mm (98.3% CI, -0.17 to 2.95 mm), respectively. There was marginal
      evidence of better Lm-Lm alignment for navigation-guided than template-assisted
      reconstruction (0.44 mm; 98.3% CI, -0.06 to 0.95 mm). Conclusions and Relevance:
      Mandible alignment following navigation-guided reconstruction is similar to
      template-assisted reconstruction. Navigation-guided alignment is likely better
      than non-template-assisted freehand reconstruction, and navigation guidance
      offers a reliable technique for real-time adjustment when reconstructing complex
      surgical defects, such as tumors effacing the buccal cortex of the mandible.

PMID- 27893004
TI  - Genetic and Environmental Factors Associated With the Ganglion Cell Complex in a
      Healthy Aging British Cohort.
AB  - Importance: Measurement of ganglion cell complex (GCC) thickness may be more
      sensitive than current methods for glaucoma diagnosis and research. However,
      little is known about the factors influencing GCC thickness in the general
      population. Objectives: To investigate the heritability of and factors associated
      with GCC thickness in a healthy aging population. Design, Setting, and
      Participants: A cross-sectional twin study was conducted from August 27, 2014, to
      March 31, 2016, among 1657 participants of white British ancestry from the
      TwinsUK study cohort without ocular pathologic conditions. Heritability analyses
      were conducted in 1432 twins (426 monozygous and 290 dizygous pairs). Association
      analyses were performed using univariable and multivariable stepwise linear
      regression models, taking family structure into account. Heritability analyses
      were conducted using maximum likelihood structural equation twin modeling. Main
      Outcomes and Measures: Parameters measured included GCC thickness,
      autorefraction, intraocular pressure, blood pressure, body mass index, and
      cholesterol, creatinine, glucose, insulin, triglycerides, and urea levels.
      Estimated glomerular filtration rate was calculated using the Modification of
      Diet in Renal Disease formula. Results: Among the 1657 participants (mean [SD]
      age, 56.0 [15.3] years; 89.5% women and 10.5% men), the mean [SD] inner GCC
      thickness was 96.0 [7.6] MUm (95% CI, 95.1-96.2). In multivariable modeling, the
      mean inner GCC thickness was associated with advancing age (beta, -0.14; P <
      .001), increased body mass index (beta, -0.15; P = .001), spherical equivalent
      (beta, 0.70; P < .001), and higher estimated glomerular filtration rate (beta,
      0.03; P = .02). A 1-U increase in age or body mass index was associated with a
      0.14-um and 0.15-um decrease in GCC thickness, respectively (P < .001), while a 1
      U increase in spherical equivalent or estimated glomerular filtration rate was
      associated with a 0.70-um (P < .001) and 0.03-um (P = .02) increase in GCC
      thickness, respectively. Ganglion cell complex thickness was not associated with
      sex, intraocular pressure, or diabetes. Age-adjusted GCC thickness was highly
      heritable, with additive genetic effects explaining 81% (95% CI, 78%-84%) of
      phenotypic variance and individual environmental factors explaining the remaining
      19% (95% CI, 16%-22%). Conclusions and Relevance: Ganglion cell complex thickness
      appears to be highly heritable and further genetic analysis may help identify new
      biological pathways for glaucoma. The results suggest it may be important to
      account for age, body mass index, refractive error, and sex when using GCC
      thickness as a diagnostic tool. Replication of their results is required, as is
      further research to explain the association between renal function and GCC
      thickness.

PMID- 27893006
TI  - What Otolaryngologists Need to Know About Hearing Aids.

PMID- 27893005
TI  - Transforming Head and Neck Surgeon Into Thyroid Expert: The 2016 Hayes Martin
      Lecture.
AB  - With the rapid rise in the incidence of thyroid cancer, the number of
      thyroidectomies has increased remarkably in the last 10 years. Thyroidectomy
      accounts for approximately 40% of the workload in head and neck fellowship. The
      decision making in thyroid surgery is quite complex, especially when patients
      present with recurrent or advanced thyroid cancer. The complications of thyroid
      surgery can be very serious in relation to quality of life. Some of these
      complications can be avoided with meticulous surgical technique. Thyroid surgery
      continues to span various specialties, and surgical volume continues to be an
      important parameter in outcomes. Technological advances have made a significant
      impact in thyroid surgery; however, these need to be carefully evaluated before
      their routine implementation and for extracervical approaches to thyroidectomy.
      The use of external radiation therapy and targeted therapies has expanded in
      recent years for patients with recurrent thyroid cancer. In a specialized and
      tertiary care center, the thyroid expert should be well-trained to make
      appropriate complex decisions. Thyroid experts should be part of the
      multidisciplinary team managing thyroid cancer from A to Z.

PMID- 27893007
TI  - Another Tattoo Reaction Pitfall: A Pink Lamb in Wolf's Clothing.

PMID- 27893008
TI  - Use of Genetic Testing in Amyotrophic Lateral Sclerosis by Neurologists.

PMID- 27893009
TI  - Lymphadenectomy for Treatment of Early-Stage Endometrial Cancer.
AB  - Clinical Question: What is the association between lymphadenectomy and survival,
      disease recurrence, and surgical morbidity in women with presumed early-stage,
      low-grade endometrial carcinoma? Bottom Line: The evidence from randomized
      clinical trials suggests that lymphadenectomy does not improve survival or
      decrease disease recurrence in women with early-stage, low-grade endometrial
      carcinoma. Furthermore lymphadenectomy is associated with an increase in both
      short- and long-term surgery-related systemic morbidity.

PMID- 27893010
TI  - Rethinking Outcomes in Leucine-Rich, Glioma-Inactivated 1 Protein Encephalitis:
      "Good" Isn't Good Enough.

PMID- 27893011
TI  - Cardiovascular Medications and Fractures: Dodging Complexity.

PMID- 27893012
TI  - Surgeons' and Trauma Care Physicians' Perception of the Impact of the
      Globalization of Medical Education on Quality of Care in Lima, Peru.
AB  - Importance: The globalization of medical education-the process by which trainees
      in any region gain access to international training (electronic or in-person)-is
      a growing trend. More data are needed to inform next steps in the responsible
      stewardship of this process, from the perspective of trainees and institutions at
      all income levels, and for use by national and international policymakers.
      Objective: To describe the impact of the globalization of medical education on
      surgical care in Peru from the perspective of Peruvian surgeons who received
      international training. Design, Setting, and Participants: Observational study of
      qualitative interviews conducted from September 2015 to January 2016 using
      grounded theory qualitative research methods. The study was conducted at 10 large
      public institutions that provide most of the trauma care in Lima, Peru, and
      included urban resident and faculty surgery and trauma care physicians.
      Exposures: Access to international surgical rotations and medical information.
      Main Outcomes and Measures: Outcome measures defining the impact of globalization
      on surgical care were developed as part of simultaneous data collection and
      analysis during qualitative research as part of a larger project on trauma
      quality improvement practices in Peru. Results: Fifty qualitative interviews of
      surgeons and emergency medicine physicians were conducted at 10 hospitals,
      including multiple from the public and social security systems. A median of 4
      interviews were conducted at each hospital, and fewer than 3 interviews were
      conducted at only 1 hospital. From the broader theme of globalization emerged
      subthemes of an eroded sense of agency and a perception of inadequate training on
      the adaptation of international standards as negative effects of globalization on
      surgical care in Peru. Access to research funds, provision of incentives for
      acquisition of advanced clinical training, increased expectations for patient
      outcomes, and education in quality improvement skills are ways in which
      globalization positively affected surgeons and their patients in Peru.
      Conclusions and Relevance: Short-term overseas training of surgeons from low- and
      middle-income countries may improve care in the surgeons' country of origin
      through the acquisition of skills and altered expectations for excellence.
      Prioritization of evidence-based medical education is necessary given widespread
      internet access and thus clinician exposure to variable quality medical
      information. Finally, the establishment of centers of excellence in low- and
      middle-income countries may address the eroded sense of agency attributable to
      globalization and offer a local example of world-class surgical outcomes,
      diminishing surgeons' most frequently cited reason for emigration: access to
      better surgical training.

PMID- 27893013
TI  - Proton Chemical Shift Imaging of the Brain in Pediatric and Adult Developmental
      Stuttering.
AB  - Importance: Developmental stuttering is a neuropsychiatric condition of
      incompletely understood brain origin. Our recent functional magnetic resonance
      imaging study indicates a possible partial basis of stuttering in circuits
      enacting self-regulation of motor activity, attention, and emotion. Objective: To
      further characterize the neurophysiology of stuttering through in vivo assay of
      neurometabolites in suspect brain regions. Design, Setting, and Participants:
      Proton chemical shift imaging of the brain was performed in a case-control study
      of children and adults with and without stuttering. Recruitment, assessment, and
      magnetic resonance imaging were performed in an academic research setting. Main
      Outcomes and Measures: Ratios of N-acetyl-aspartate plus N-acetyl-aspartyl
      glutamate (NAA) to creatine (Cr) and choline compounds (Cho) to Cr in widespread
      cerebral cortical, white matter, and subcortical regions were analyzed using
      region of interest and data-driven voxel-based approaches. Results: Forty-seven
      children and adolescents aged 5 to 17 years (22 with stuttering and 25 without)
      and 47 adults aged 21 to 51 years (20 with stuttering and 27 without) were
      recruited between June 2008 and March 2013. The mean (SD) ages of those in the
      stuttering and control groups were 12.2 (4.2) years and 13.4 (3.2) years,
      respectively, for the pediatric cohort and 31.4 (7.5) years and 30.5 (9.9) years,
      respectively, for the adult cohort. Region of interest-based findings included
      lower group mean NAA:Cr ratio in stuttering than nonstuttering participants in
      the right inferior frontal cortex (-7.3%; P = .02), inferior frontal white matter
      (-11.4%; P < .001), and caudate (-10.6%; P = .04), while the Cho:Cr ratio was
      higher in the bilateral superior temporal cortex (left: +10.0%; P = .03 and
      right: +10.8%; P = .01), superior temporal white matter (left: +14.6%; P = .003
      and right: +9.5%; P = .02), and thalamus (left: +11.6%; P = .002 and right:
      +11.1%; P = .001). False discovery rate-corrected voxel-based findings were
      highly consistent with region of interest findings. Additional voxel-based
      findings in the stuttering sample included higher NAA:Cr and Cho:Cr ratios
      (regression coefficient, 197.4-275; P < .001) in the posterior cingulate, lateral
      parietal, hippocampal, and parahippocampal cortices and amygdala, as well as
      lower NAA:Cr and Cho:Cr ratios (regression coefficient, 119.8-275; P < .001) in
      the superior frontal and frontal polar cortices. Affected regions comprised nodes
      of the Bohland speech-production (motor activity regulation), default-mode
      (attention regulation), and emotional-memory (emotion regulation) networks.
      Regional correlations were also observed between local metabolites and stuttering
      severity (r = 0.40-0.52; P = .001-.02). Conclusions and Relevance: This
      spectroscopy study of stuttering demonstrates brainwide neurometabolite
      alterations, including several regions implicated by other neuroimaging
      modalities. Prior ascription of a role in stuttering to inferior frontal and
      superior temporal gyri, caudate, and other structures is affirmed. Consistent
      with prior functional magnetic resonance imaging findings, these results further
      intimate neurometabolic aberrations in stuttering in brain circuits subserving
      self-regulation of speech production, attention, and emotion.

PMID- 27893014
TI  - Durability of the Rituximab Response in Acetylcholine Receptor Autoantibody
      Positive Myasthenia Gravis.
AB  - Importance: Myasthenia gravis (MG), an autoimmune disorder of neuromuscular
      transmission, is treated by an array of immunotherapeutics, many of which are
      nonspecific. Even with current therapies, a subset of patients has medically
      refractory MG. The benefits of B-cell-targeted therapy with rituximab have been
      observed in MG; however, the duration of these benefits after treatment is
      unclear. Objective: To evaluate the durability of response to rituximab in the
      treatment of acetylcholine receptor autoantibody-positive (AChR+) generalized MG.
      Design, Setting and Participants: This retrospective case series study included
      16 patients with AChR+ MG referred to an MG clinic from January 1, 2007, to
      December 31, 2015. The patients were treated with rituximab and followed up for
      18 to 84 months after treatment. Main Outcomes and Measures: Assessment of long
      term clinical response, durability of response and/or relapse rate, AChR
      autoantibody levels, adverse effects, and inflammatory markers. Results: In the
      16 patients (6 men and 10 women; median age, 42 [range, 18-69] years), clinical
      improvement was observed in parallel with complete withdrawal or reduction of
      other immunotherapies, with all patients achieving complete stable remission,
      pharmacologic remission, or minimal manifestations based on the Myasthenia Gravis
      Foundation of America postintervention status criteria. Nine patients (56%) had a
      relapse during a mean follow-up of 36 (range, 24-47) months. Seven patients (44%)
      remained relapse free with a mean follow-up of 47 (range, 18-81) months since the
      last rituximab treatment. All values were normalized to a pretreatment anti-AChR
      antibody level of 100% and the mean levels after each rituximab cycle were
      calculated. A 33% decrease was seen after cycle 1 of rituximab treatment (100% vs
      67%; P = .004); 20% after cycle 2 (compared with cycle 1) (67% vs 47%; P = .008);
      and 17% after cycle 3 (compared with cycle 2) (47% vs 30%; P = .02). However, the
      serum cytokine levels measured were found to be unchanged. Conclusions and
      Relevance: Rituximab therapy appears to be an effective option in patients with
      refractory AChR+ MG, who were observed to have a durable response after
      treatment. Identification of markers of disease relapse and sustained remission
      are critical next steps in the development of pathophysiology-relevant, evidence
      based practice parameters for rituximab in the treatment of MG.

PMID- 27893015
TI  - Dementia Trends in the United States: Read Up and Weigh In.

PMID- 27893016
TI  - Highlights in Head and Neck Cancer.

PMID- 27893017
TI  - Evaluation of Cognitive Deficits and Structural Hippocampal Damage in
      Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies.
AB  - Importance: Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1)
      antibodies is one of the most frequent variants of autoimmune encephalitis with
      antibodies targeting neuronal surface antigens. However, the neuroimaging pattern
      and long-term cognitive outcome are not well understood. Objective: To study
      cognitive outcome and structural magnetic resonance imaging (MRI) alterations in
      patients with anti-LGI1 encephalitis. Design, Setting, and Participants: A cross
      sectional study was conducted at the Departments of Neurology at Charite
      Universitatsmedizin Berlin and University Hospital Schleswig-Holstein, Kiel,
      Germany. Data on 30 patients with anti-LGI1 encephalitis and 27 healthy control
      individuals matched for age, sex, and educational level were collected from June
      1, 2013, through February 28, 2015. Main Outcomes and Measures: Clinical
      assessment, cognitive testing, and high-resolution MRI data, including whole
      brain, hippocampal and basal ganglia volumetry; white matter integrity (diffusion
      tensor imaging); gray matter density (voxel-based morphometry); and hippocampal
      microstructural integrity (mean diffusivity and fractional anisotropy). Results:
      Of the 30 patients included in the study, 19 were male (63%); mean (SD) age was
      65.7 (12.3) years. Patients with anti-LGI1 encephalitis had incomplete recovery
      with significant and persisting verbal (mean [SE] Rey Auditory Verbal Learning
      Test [RAVLT], delayed recall: patients, 6.52 [1.05]; controls, 11.78 [0.56], P <
      .001) and visuospatial (Rey-Osterrieth Complex Figure Test [ROCF], delayed
      recall: patients, 16.0 [1.96]; controls, 25.86 [1.24]; P < .001) memory deficits.
      These deficits were accompanied by pronounced hippocampal atrophy, including
      subfields cornu ammonis 2/3 (CA2/3) and CA4/dentate gyrus (DG), as well as
      impaired hippocampal microstructural integrity. Higher disease severity
      correlated with larger verbal memory deficits (RAVLT delayed recall, r = -0.40; P
      = .049), decreased volumes of left hippocampus (r = -0.47; P = .02) and left
      CA2/3 (r = -0.41; P = .04) and CA4/DG (r = -0.43; P = .03) subfields, and
      impaired left hippocampal microstructural integrity (r = 0.47; P = .01). In turn,
      decreased volume of the left CA2/3 subfield (RAVLT delayed recall, r = 0.40; P =
      .047) and impaired left hippocampal microstructural integrity (RAVLT recognition,
      r = -0.41; P = .04) correlated with verbal memory deficits. Basal ganglia MRI
      signal abnormalities were observed in only 1 patient, but a longer duration of
      faciobrachial dystonic seizures correlated with a reduction of pallidum volume (r
      = -0.71; P = .03). In contrast, no abnormalities of cortical gray matter or white
      matter were found. The latency between disease onset and initiation of
      immunotherapy was significantly correlated with verbal (RAVLT recall after
      interference, r = -0.48; P = .02) and visuospatial (ROCF delayed recall, r = 
      0.46; P = .03) memory deficits. Conclusions and Relevance: Anti-LGI1 encephalitis
      is associated with cognitive deficits and disability as a result of structural
      damage to the hippocampal memory system. This damage might be prevented by early
      immunotherapy.

PMID- 27893018
TI  - Effect of omega-3 Polyunsaturated Fatty Acids in Young People at Ultrahigh Risk
      for Psychotic Disorders: The NEURAPRO Randomized Clinical Trial.
AB  - Importance: A promising treatment to prevent onset and improve outcomes in
      patients at ultrahigh risk for psychosis is dietary supplementation with long
      chain omega-3 polyunsaturated fatty acids (PUFAs). Objective: To determine
      whether treatment with omega-3 PUFAs in combination with a high-quality
      psychosocial intervention (cognitive behavioral case management [CBCM]) is more
      effective than placebo plus CBCM. Design, Setting, and Participants: NEURAPRO, a
      double-blind, placebo-controlled, randomized clinical trial, was conducted from
      March 1, 2010, to September 30, 2014, in 10 specialized early psychosis treatment
      services in Australia, Asia, and Europe. The primary analysis used the intention
      to-treat approach. Interventions: A daily dose of 1.4 g of omega-3 PUFAs or
      placebo (paraffin oil), plus 20 or fewer sessions of CBCM over the 6-month study
      period. Main Outcomes and Measures: The primary outcome was transition to
      psychosis status at 6 months. The secondary outcomes were general levels of
      psychopathology and functioning, as assessed by the Brief Psychiatric Rating
      Scale (BPRS) (range, 24-168), Scale for the Assessment of Negative Symptoms
      (SANS) (range, 0-125), Montgomery-Asberg Depression Rating Scale (MADRS) (range,
      0-60), Young Mania Rating Scale (YMRS) (range, 0-44), Social and Occupational
      Functioning Assessment Scale (SOFAS) (range, 0-100), and the Global Functioning:
      Social and Role scale (range, 0-10). For SOFAS and Global Functioning: Social and
      Role scale, higher scores were better; for other measures, lower scores were
      better. Results: In this study of 304 adults at ultrahigh risk for psychotic
      disorders, 153 (50.3%) received omega-3 PUFAs and 151 (49.7%) received placebo.
      In all, 139 (45.7%) were male; mean (SD) age was 19.1 (4.6) years. The Kaplan
      Meier-estimated 6-month transition rates were 5.1% (95% CI, 1.3%-8.7%) in the
      control group and 6.7% (95% CI, 2.3%-10.8%) in the omega-3 PUFA group. At 12
      months, the rates were 11.2% (95% CI, 5.5%-16.7%) in the control group and 11.5%
      (95% CI, 5.8%-16.9%) in the omega-3 PUFA group. No significant difference was
      observed between the transition rates of both groups (hazard ratio, 1.1; 95% CI,
      0.55-2.23; P = .76, stratified log-rank test). Conclusions and Relevance: This
      trial clearly failed to replicate the findings of the original single-center
      trial. The most likely explanation is that omega-3 PUFAs lack efficacy under
      these conditions. However, the lower-than-expected transition rate may have
      prevented a test of the main hypothesis. Given the substantial symptomatic and
      functional improvement in both groups, the other treatments received (ie, CBCM
      and antidepressants) likely produced a ceiling effect beyond which omega-3 PUFAs,
      even if effective, could not be shown to confer additional benefits.
      Nevertheless, the main conclusion is that omega-3 PUFAs are not effective under
      conditions where good quality, evidence-based psychosocial treatment is
      available. Trial Registration: anzctr.org.au Identifier: 12608000475347.

PMID- 27893019
TI  - Occurrence of Bruise, Hematoma, and Pain in Upper Blepharoplasty Using Blunt
      Needle vs Sharp-Needle Anesthetic Injection in Upper Blepharoplasty: A Randomized
      Clinical Trial.
AB  - Importance: Though it has been a common practice to use sharp needles to
      administer local anesthesia for upper blepharoplasty, the evidence for their
      benefit is lacking. Objective: To evaluate whether there is any benefit of using
      blunt-needle injection for local anesthesia when performing upper blepharoplasty
      to reduce postoperative bruise, hematoma, and pain. Design, Setting, and
      Participants: Randomized clinical trial of 44 patients who underwent bilateral
      upper blepharoplasty in an academic medical setting were randomized to receive
      local anesthesia injections (lidocaine, 2%; 27-gauge needle) with a blunt needle
      in one eyelid and a sharp needle in the other eyelid. Main Outcomes and Measures:
      Visual analog scale (VAS) score of 0 to 10 (lower score indicating lower level of
      pain) was used to blindly assess pain in patients receiving anesthesia injections
      with both needle types. After injection and skin incision, photographs of the
      eyelids of each patient were taken and used by 2 blinded observers to identify
      bruise or hematoma. Results: In the 44 patients (88 eyelids) included in the
      study (all women; mean age, 31 years; age range, 18-56 years) bruise or hematoma
      occurred at the sharp-needle injection site in 11 women (25%) vs 0 women at the
      blunt-needle site (P < .001). The mean VAS scores were 5.48 and 4.64 for pain
      assessed at sites of sharp- and blunt-needle injections, respectively (P = .002).
      Conclusions and Relevance: Use of blunt needles to administer local anesthesia
      when performing upper blepharoplasty is less likely to cause hemorrhage and
      require interventional pain procedures than use of sharp needles. Therefore, for
      a more accurate surgical procedure and faster recovery, a blunt needle may be a
      preferable choice. The use of the blunt needle presents fewer complications and
      allows more accurate and refined work with faster patient recovery. Level of
      Evidence: 1. Trial Registration: Chinese Clinical Trial Registry identifier:
      ChiCTR-ONC-16007979.

PMID- 27893021
TI  - Mitigating Financial Toxicity Among US Patients With Cancer.

PMID- 27893020
TI  - Assessment of the EuroQol 5-Dimension Questionnaire for Detection of Clinically
      Significant Global Health-Related Quality-of-Life Improvement Following
      Functional Septorhinoplasty.
AB  - Importance: Nasal airway obstruction is a common presenting complaint among
      patients in otolaryngology practices, and its treatment necessitates critical
      outcomes evaluation and cost-utility analysis. Objective: To evaluate the utility
      and applicability of the EuroQol 5-Dimension (EQ5D) global health-related quality
      of-life (HRQoL) questionnaire for the assessment of clinical outcomes in
      functional septorhinoplasty. Design, Setting, and Participants: Prospective
      cohort study at a university-based tertiary medical center of patients undergoing
      functional septorhinoplasty for treatment of nasal obstruction. Interventions:
      Patient demographic characteristics, operative intervention, and preoperative and
      postoperative Nasal Obstruction Symptom Evaluation (NOSE) and EQ5D scores were
      collected and analyzed between November 2013 and June 2016. Main Outcomes and
      Measures: Comparison of preoperative and postoperative EQ5D and NOSE scores at 2
      and 6 or more months following surgery (long-term follow-up). Results: A total of
      135 patients (56.3% male; mean [SD] age, 36.8 [14.8] years) completed EQ5D and
      NOSE surveys preoperatively and postoperatively, with mean (SD) follow-up of 5.82
      (4.1) months. Of these, 117 completed the 2-month survey and 64 completed their
      last survey at 6 or more months. Baseline NOSE and EQ5D visual analog scale (VAS)
      scores were moderately correlated (r = -0.37, P < .001) as were changes in NOSE
      and EQ5D VAS scores at long-term follow-up (r = -0.33, P = .007). Mean baseline
      NOSE score of 64.3 (95% CI, 60.5-68.2) decreased to 24.8 (95% CI, 18.8-30.9) at
      long-term follow-up (P < .001). The frequency of patients reporting problems in
      the EQ5D domains of pain/discomfort and usual activity decreased by more than
      half in the long-term follow-up group (30 [47%] vs 14 [22%] and 11 [17%] vs 4
      [6%]; P = .002 and .02, respectively). The minimal clinically important
      difference of the EQ5D VAS score was calculated at 9.5. The EQ5D VAS scores had
      statistically and clinically significant improvement at long-term follow-up in
      patients with NOSE score improvements of 30 to 60 points (EQ5D VAS increased from
      mean [SD] of 72.3 [20] to 85.9 [10]; P < .001) and 65 to 100 points (EQ5D VAS
      increased from mean [SD] of 66.2 [25] to 82.0 [13]; P = .01). Conclusions and
      Relevance: The EQ5D, a global HRQoL instrument, was able to detect clinically
      significant improvement following functional septorhinoplasty for nasal
      obstruction. Nasal valve correction improved not only disease-specific quality of
      life but also global HRQoL. The ability to calculate health utility values from
      the EQ5D and its low response burden make it an attractive tool for
      septorhinoplasty outcomes research. Level of Evidence: 4.

PMID- 27893022
TI  - Suicide Attempts Among US Army Soldiers-Reply.

PMID- 27893023
TI  - Patient-Reported Outcome Measures for Facial Plastic Surgery: A Specialty Finally
      Gets to Go to the PROM.

PMID- 27893024
TI  - Glycemic Control and Functional Decline in Nursing Home Residents With Diabetes.

PMID- 27893025
TI  - Medicare's Shift to Mandatory Alternative Payment Models: Why Surgeons Should
      Care.

PMID- 27893026
TI  - Prevalence of Depression in Patients With Mild Cognitive Impairment: A Systematic
      Review and Meta-analysis.
AB  - Importance: Depression is common in individuals with mild cognitive impairment
      (MCI) and may confer a higher likelihood of progression to dementia. Prevalence
      estimates of depression in those with MCI are required to guide both clinical
      decisions and public health policy, but published results are variable and lack
      precision. Objective: To provide a precise estimate of the prevalence of
      depression in individuals with MCI and identify reasons for heterogeneity in the
      reported results. Data Sources: A search of literature from database inception to
      March 2016 was performed using Medline, Embase, and PsycINFO. Hand searching of
      all included articles was performed, including a Google Scholar search of
      citations of included articles. Study Selection: Articles were included if they
      (1) were published in English, (2) reported patients with MCI as a primary study
      group, (3) reported depression or depressive symptoms using a validated
      instrument, and (4) reported the prevalence of depression in patients with MCI.
      Data Extraction and Synthesis: All abstracts, full-text articles, and other
      sources were reviewed, with data extracted in duplicate. The overall prevalence
      of depression in patients with MCI was pooled using a random-effects model.
      Heterogeneity was explored using stratification and random-effects meta
      regression. Main Outcomes and Measures: The prevalence of depression in patients
      with MCI, reported as a percentage with 95% CIs. Estimates were also stratified
      by population source (community-based or clinic-based sample), method of
      depression diagnosis (clinician-administered, informant-based, or self-report),
      and method of MCI diagnosis (cognitive vs global measure and amnestic vs
      nonamnestic). Results: Of 5687 unique abstracts, 255 were selected for full-text
      review, and 57 studies, representing 20 892 patients, met all inclusion criteria.
      The overall pooled prevalence of depression in patients with MCI was 32% (95% CI,
      27-37), with significant heterogeneity between estimates (I2 = 90.7%). When
      stratified by source, the prevalence of depression in patients with MCI in
      community-based samples was 25% (95% CI, 19-30) and was 40% (95% CI, 32-48) in
      clinic-based samples, which was significantly different (P < .001). The method
      used to diagnose depression did not significantly influence the prevalence
      estimate, nor did the criteria used for MCI diagnosis or MCI subtype. Conclusions
      and Relevance: The prevalence of depression in patients with MCI is high. A
      contributor to heterogeneity in the reported literature is the source of the
      sample, with greater depression burden prevalent in clinic-based samples.

PMID- 27893027
TI  - Errors in Table.

PMID- 27893029
TI  - Androgen Deprivation Therapy and Dose-Escalated Radiotherapy for Intermediate-
      and High-Risk Prostate Cancer-Reply.

PMID- 27893028
TI  - Out-of-Pocket Spending and Financial Burden Among Medicare Beneficiaries With
      Cancer.
AB  - Importance: Medicare beneficiaries with cancer are at risk for financial hardship
      given increasingly expensive cancer care and significant cost sharing by
      beneficiaries. Objectives: To measure out-of-pocket (OOP) costs incurred by
      Medicare beneficiaries with cancer and identify which factors and services
      contribute to high OOP costs. Design, Setting, and Participants: We prospectively
      collected survey data from 18 166 community-dwelling Medicare beneficiaries,
      including 1409 individuals who were diagnosed with cancer during the study
      period, who participated in the January 1, 2002, to December 31, 2012, waves of
      the Health and Retirement Study, a nationally representative panel study of US
      residents older than 50 years. Data analysis was performed from July 1, 2014, to
      June 30, 2015. Main Outcomes and Measures: Out-of-pocket medical spending and
      financial burden (OOP expenditures divided by total household income). Results:
      Among the 1409 participants (median age, 73 years [interquartile range, 69-79
      years]; 46.4% female and 53.6% male) diagnosed with cancer during the study
      period, the type of supplementary insurance was significantly associated with
      mean annual OOP costs incurred after a cancer diagnosis ($2116 among those
      insured by Medicaid, $2367 among those insured by the Veterans Health
      Administration, $5976 among those insured by a Medicare health maintenance
      organization, $5492 among those with employer-sponsored insurance, $5670 among
      those with Medigap insurance coverage, and $8115 among those insured by
      traditional fee-for-service Medicare but without supplemental insurance
      coverage). A new diagnosis of cancer or common chronic noncancer condition was
      associated with increased odds of incurring costs in the highest decile of OOP
      expenditures (cancer: adjusted odds ratio, 1.86; 95% CI, 1.55-2.23; P < .001;
      chronic noncancer condition: adjusted odds ratio, 1.82; 95% CI, 1.69-1.97; P <
      .001). Beneficiaries with a new cancer diagnosis and Medicare alone incurred OOP
      expenditures that were a mean of 23.7% of their household income; 10% of these
      beneficiaries incurred OOP expenditures that were 63.1% of their household
      income. Among the 10% of beneficiaries with cancer who incurred the highest OOP
      costs, hospitalization contributed to 41.6% of total OOP costs. Conclusions and
      Relevance: Medicare beneficiaries without supplemental insurance incur
      significant OOP costs following a diagnosis of cancer. Costs associated with
      hospitalization may be a primary contributor to these high OOP costs. Medicare
      reform proposals that restructure the benefit design for hospital-based services
      and incorporate an OOP maximum may help alleviate financial burden, as can
      interventions that reduce hospitalization in this population.

PMID- 27893031
TI  - The beta-HPV Subtypes-Cornerstone of the Next-Generation Vaccine.

PMID- 27893030
TI  - Development and Initial Validation of the Risk Analysis Index for Measuring
      Frailty in Surgical Populations.
AB  - Importance: Growing consensus suggests that frailty-associated risks should
      inform shared surgical decision making. However, it is not clear how best to
      screen for frailty in preoperative surgical populations. Objective: To develop
      and validate the Risk Analysis Index (RAI), a 14-item instrument used to measure
      surgical frailty. It can be calculated prospectively (RAI-C), using a clinical
      questionnaire, or retrospectively (RAI-A), using variables from the surgical
      quality improvement databases (Veterans Affairs or American College of Surgeons
      National Surgical Quality Improvement Projects). Design, Setting, and
      Participants: Single-site, prospective cohort from July 2011 to September 2015 at
      the Veterans Affairs Nebraska-Western Iowa Heath Care System, a Level 1b Veterans
      Affairs Medical Center. The study included all patients presenting to the medical
      center for elective surgery. Exposures: We assessed the RAI-C for all patients
      scheduled for surgery, linking these scores to administrative and quality
      improvement data to calculate the RAI-A and the modified Frailty Index. Main
      Outcomes and Measures: Receiver operator characteristics and C statistics for
      each measure predicting postoperative mortality and morbidity. Results: Of the
      participants, the mean (SD) age was 60.7 (13.9) years and 249 participants (3.6%)
      were women. We assessed the RAI-C 10 698 times, from which we linked 6856 unique
      patients to mortality data. The C statistic predicting 180-day mortality for the
      RAI-C was 0.772. Of these 6856 unique patients, we linked 2785 to local Veterans
      Affairs Surgeons National Surgical Quality Improvement Projects data and
      calculated the C statistic for both the RAI-A (0.823) and RAI-C (0.824), along
      with the correlation between the 2 scores (r = 0.478; P < .001). Of these 2785
      patients, there were sufficient data to calculate the modified Frailty Index for
      1021, in which the C statistics were 0.865 (RAI-A), 0.797 (RAI-C), and 0.811
      (modified Frailty Index). The correlation between the RAI-A and RAI-C was 0.547,
      and the correlations of the modified Frailty Index to the RAI-A and RAI-C were
      0.301 and 0.269, respectively (all P < .001). A cutoff of RAI-C of at least 21
      classified 18.3% patients as "frail" with a sensitivity of 0.50 and specificity
      of 0.82, whereas the RAI-A was less sensitive (0.25) and more specific (0.97),
      classifying only 3.7% as "frail." Conclusions and Relevance: The RAI-C and RAI-A
      represent effective tools for measuring frailty in surgical populations with
      predictive ability on par with other frailty tools. Moderate correlation between
      the measures suggests convergent validity. The RAI-C offers the advantage of
      prospective, preoperative assessment that is proved feasible for large-scale
      screening in clinical practice. However, further efforts should be directed at
      determining the optimal components of preoperative frailty assessment.

PMID- 27893032
TI  - Effect of Group vs Individual Cognitive Processing Therapy in Active-Duty
      Military Seeking Treatment for Posttraumatic Stress Disorder: A Randomized
      Clinical Trial.
AB  - Importance: Cognitive processing therapy (CPT), an evidence-based treatment for
      posttraumatic stress disorder (PTSD), has not been tested as an individual
      treatment among active-duty military. Group CPT may be an efficient way to
      deliver treatment. Objective: To determine the effects of CPT on PTSD and co
      occurring symptoms and whether they differ when administered in an individual or
      a group format. Design, Setting, and Participants: In this randomized clinical
      trial, 268 active-duty servicemembers consented to assessment at an army medical
      center from March 8, 2012, to September 23, 2014, and were randomized to group or
      individual CPT. Inclusion criteria were PTSD after military deployment and stable
      medication therapy. Exclusion criteria consisted of suicidal or homicidal intent
      or psychosis. Data collection was completed on June 15, 2015. Analysis was based
      on intention to treat. Interventions: Participants received CPT (the version
      excluding written accounts) in 90-minute group sessions of 8 to 10 participants
      (15 cohorts total; 133 participants) or 60-minute individual sessions (135
      participants) twice weekly for 6 weeks. The 12 group and individual sessions were
      conducted concurrently. Main Outcomes and Measures: Primary measures were scores
      on the Posttraumatic Symptom Scale-Interview Version (PSS-I) and the stressor
      specific Posttraumatic Stress Disorder Checklist (PCL-S); secondary measures were
      scores on the Beck Depression Inventory-II (BDI-II) and the Beck Scale for
      Suicidal Ideation (BSSI). Assessments were completed by independent evaluators
      masked to treatment condition at baseline and 2 weeks and 6 months after
      treatment. Results: Among the 268 participants (244 men [91.0%]; 24 women [9.0%];
      mean [SD] age, 33.2 [7.4] years), improvement in PTSD severity at posttreatment
      was greater when CPT was administered individually compared with the group format
      (mean [SE] difference on the PSS-I, -3.7 [1.4]; Cohen d = 0.6; P = .006).
      Significant improvements were maintained with the individual (mean [SE] PSS-I, 
      7.8 [1.0]; Cohen d = 1.3; mean [SE] PCL-S, -12.6 [1.4]; Cohen d = 1.2) and group
      (mean [SE] PSS-I, -4.0 [0.97]; Cohen d = 0.7; mean [SE] PCL-S, -6.3 [1.4]; Cohen
      d = 0.6) formats, with no differences in remission or severity of PTSD at the 6
      month follow-up. Symptoms of depression and suicidal ideation did not differ
      significantly between formats. Conclusions and Relevance: Individual treatment
      resulted in greater improvement in PTSD severity than group treatment. Depression
      and suicidal ideation improved equally with both formats. However, even among
      those receiving individual CPT, approximately 50% still had PTSD and clinically
      significant symptoms. In the military population, improving existing treatments
      such as CPT or developing new treatments is needed. Trial Registration:
      clinicaltrials.gov identifier: NCT02173561.

PMID- 27893035
TI  - Suicide Attempts Among US Army Soldiers.

PMID- 27893036
TI  - omega-3 Polyunsaturated Fatty Acids to Prevent Psychosis: The Importance of
      Replication Studies.

PMID- 27893034
TI  - Quality of Abstracts Reporting Randomized Clinical Trials Presented at a Major
      Oncology Conference.

PMID- 27893037
TI  - Refining Trauma-Focused Treatments for Servicemembers and Veterans With
      Posttraumatic Stress Disorder: Progress and Ongoing Challenges.

PMID- 27893033
TI  - Effect of a Decision Aid on Access to Total Knee Replacement for Black Patients
      With Osteoarthritis of the Knee: A Randomized Clinical Trial.
AB  - Importance: Black patients with advanced osteoarthritis (OA) of the knee are
      significantly less likely than white patients to undergo surgery. No strategies
      have been proved to improve access to surgery for black patients with end-stage
      OA of the knee. Objective: To assess whether a decision aid improves access to
      total knee replacement (TKR) surgery for black patients with OA of the knee.
      Design, Setting, and Participants: In a randomized clinical trial, 336 eligible
      participants who self-identified as black and 50 years or older with chronic and
      frequent knee pain, a Western Ontario McMaster Universities Osteoarthritis Index
      score of at least 39, and radiographic evidence of OA of the knee were recruited
      from December 1, 2010, to May 31, 2014, at 3 medical centers. Exclusion criteria
      were history of major joint replacement, terminal illness, inflammatory
      arthritis, prosthetic leg, cognitive impairment, lack of a telephone, or
      contraindications to elective replacement surgery. Data were analyzed on a per
      protocol and intention-to-treat (ITT) basis. Exposure: Access to a decision aid
      for OA of the knee, a 40-minute video that describes the risks and benefits of
      TKR surgery. Main Outcomes and Measures: Receipt of TKR surgery within 12 months
      and/or a recommendation for TKR surgery from an orthopedic surgeon within 6
      months after the intervention. Results: Among 336 patients (101 men [30.1%]; 235
      women [69.9%]; mean [SD] age, 59.1 [7.2] years) randomized to the intervention or
      control group, 13 of 168 controls (7.7%) and 25 of 168 intervention patients
      (14.9%) underwent TKR within 12 months (P = .04). These changes represent a 70%
      increase in the TKR rate, which increased by 86% (11 of 154 [7.1%] vs 23 of 150
      [15.3%]; P = .02) in the per-protocol sample. Twenty-six controls (15.5%) and 34
      intervention patients (20.2%) in the ITT analysis received a recommendation for
      surgery within 6 months (P = .25). The difference in the surgery recommendation
      rate between the controls (24 of 154 [15.6%]) and the intervention group (31 of
      150 [20.7%]) in the per-protocol analysis also was not statistically significant
      (P = .25). Adjustment for study site yielded similar results: for receipt of TKR
      at 12 months, adjusted ORs were 2.10 (95% CI, 1.04-4.27) for the ITT analysis and
      2.39 (95% CI, 1.12-5.10) for the per-protocol analysis; for recommendation of TKR
      at 6 months, 1.39 (95% CI, 0.79-2.44) and 1.41 (95% CI, 0.78-2.55). Conclusions
      and Relevance: A decision aid increased rates of TKR among black patients.
      However, rates of recommendation for surgery did not differ significantly. A
      patient-centered counseling and educational intervention may help to address
      racial variations in the use of TKR for the management of end-stage OA of the
      knee. Trial Registration: clinicaltrials.gov Identifer: NCT01851785.

PMID- 27893038
TI  - Targeting the PI3K/AKT/mTOR Pathway for the Treatment of Mesenchymal Triple
      Negative Breast Cancer: Evidence From a Phase 1 Trial of mTOR Inhibition in
      Combination With Liposomal Doxorubicin and Bevacizumab.
AB  - Importance: Triple-negative breast cancer (TNBC) classified by transcriptional
      profiling as the mesenchymal subtype frequently harbors aberrations in the
      phosphoinositide 3-kinase (PI3K) pathway, raising the possibility of targeting
      this pathway to enhance chemotherapy response. Up to 30% of mesenchymal TNBC can
      be classified histologically as metaplastic breast cancer, a chemorefractory
      group of tumors with a mixture of epithelial and mesenchymal components
      identifiable by light microscopy. While assays to identify mesenchymal TNBC are
      under development, metaplastic breast cancer serves as a clinically identifiable
      surrogate to evaluate potential regimens for mesenchymal TNBC. Objective: To
      assess safety and efficacy of mammalian target of rapamycin (mTOR) inhibition in
      combination with liposomal doxorubicin and bevacizumab in patients with advanced
      metaplastic TNBC. Design, Setting, and Participants: Phase 1 study with dose
      escalation and dose expansion at the University of Texas MD Anderson Cancer
      Center of patients with advanced metaplastic TNBC. Patients were enrolled from
      April 16, 2009, to November 4, 2014, and followed for outcomes with a cutoff date
      of November 1, 2015, for data analysis. Interventions: Liposomal doxorubicin,
      bevacizumab, and the mTOR inhibitors temsirolimus or everolimus using 21-day
      cycles. Main Outcomes and Measures: Safety and response. When available, archived
      tissue was evaluated for aberrations in the PI3K pathway. Results: Fifty-two
      women with metaplastic TNBC (median age, 58 years; range, 37-79 years) were
      treated with liposomal doxorubicin, bevacizumab, and temsirolimus (DAT) (N = 39)
      or liposomal doxorubicin, bevacizumab, and everolimus (DAE) (N = 13). The
      objective response rate was 21% (complete response = 4 [8%]; partial response = 7
      [13%]) and 10 (19%) patients had stable disease for at least 6 months, for a
      clinical benefit rate of 40%. Tissue was available for testing in 43 patients,
      and 32 (74%) had a PI3K pathway aberration. Presence of PI3K pathway aberration
      was associated with a significant improvement in objective response rate (31% vs
      0%; P = .04) but not clinical benefit rate (44% vs 45%; P > .99). Conclusions and
      Relevance: Using metaplastic TNBC as a surrogate for mesenchymal TNBC, DAT and
      DAE had notable activity in mesenchymal TNBC. Objective response was limited to
      patients with PI3K pathway aberration. A randomized trial should be performed to
      test DAT and DAE for metaplastic TNBC, as well as nonmetaplastic, mesenchymal
      TNBC, especially when PI3K pathway aberrations are identified.

PMID- 27893039
TI  - Cyclic Mechanical Loading Enhances Transport of Antibodies Into Articular
      Cartilage.
AB  - The goal of this study was to characterize antibody penetration through cartilage
      tissue under mechanical loading. Mechanical stimulation aids in the penetration
      of some proteins, but this effect has not characterized molecules such as
      antibodies (>100 kDa), which may hold some clinical value for treating
      osteoarthritis (OA). For each experiment, fresh articular cartilage plugs were
      obtained and exposed to fluorescently labeled antibodies while under cyclic
      mechanical load in unconfined compression for several hours. Penetration of these
      antibodies was quantified using confocal microscopy, and finite element (FE)
      simulations were conducted to predict fluid flow patterns within loaded samples.
      Transport enhancement followed a linear trend with strain amplitude (0.25-5%) and
      a nonlinear trend with frequency (0.25-2.60 Hz), with maximum enhancement found
      to be at 5% cyclic strain and 1 Hz, respectively. Regions of highest enhancement
      of transport within the tissue were associated with the regions of highest
      interstitial fluid velocity, as predicted from finite-element simulations.
      Overall, cyclic compression-enhanced antibody transport by twofold to threefold.
      To our knowledge, this is the first study to test how mechanical stimulation
      affects the diffusion of antibodies in cartilage and suggest further study into
      other important factors regarding macromolecular transport.

PMID- 27893040
TI  - Association of a Dedicated Post-Hospital Discharge Follow-up Visit and 30-Day
      Readmission Risk in a Medicare Advantage Population.

PMID- 27893042
TI  - Androgen Deprivation Therapy and Dose-Escalated Radiotherapy for Intermediate-
      and High-Risk Prostate Cancer: Sign of Changing Times?

PMID- 27893043
TI  - Appropriate Use of High-Sensitivity Cardiac Troponin Levels in Patients With
      Suspected Acute Myocardial Infarction.

PMID- 27893041
TI  - A Comparison of the Prevalence of Dementia in the United States in 2000 and 2012.
AB  - Importance: The aging of the US population is expected to lead to a large
      increase in the number of adults with dementia, but some recent studies in the
      United States and other high-income countries suggest that the age-specific risk
      of dementia may have declined over the past 25 years. Clarifying current and
      future population trends in dementia prevalence and risk has important
      implications for patients, families, and government programs. Objective: To
      compare the prevalence of dementia in the United States in 2000 and 2012. Design,
      Setting, and Participants: We used data from the Health and Retirement Study
      (HRS), a nationally representative, population-based longitudinal survey of
      individuals in the United States 65 years or older from the 2000 (n = 10 546) and
      2012 (n = 10 511) waves of the HRS. Main Outcomes and Measures: Dementia was
      identified in each year using HRS cognitive measures and validated methods for
      classifying self-respondents, as well as those represented by a proxy. Logistic
      regression was used to identify socioeconomic and health variables associated
      with change in dementia prevalence between 2000 and 2012. Results: The study
      cohorts had an average age of 75.0 years (95% CI, 74.8-75.2 years) in 2000 and
      74.8 years (95% CI, 74.5-75.1 years) in 2012 (P = .24); 58.4% (95% CI, 57.3%
      59.4%) of the 2000 cohort was female compared with 56.3% (95% CI, 55.5%-57.0%) of
      the 2012 cohort (P < .001). Dementia prevalence among those 65 years or older
      decreased from 11.6% (95% CI, 10.7%-12.7%) in 2000 to 8.8% (95% CI, 8.2%-9.4%)
      (8.6% with age- and sex-standardization) in 2012 (P < .001). More years of
      education was associated with a lower risk for dementia, and average years of
      education increased significantly (from 11.8 years [95% CI, 11.6-11.9 years] to
      12.7 years [95% CI, 12.6-12.9 years]; P < .001) between 2000 and 2012. The
      decline in dementia prevalence occurred even though there was a significant age-
      and sex-adjusted increase between years in the cardiovascular risk profile (eg,
      prevalence of hypertension, diabetes, and obesity) among older US adults.
      Conclusions and Relevance: The prevalence of dementia in the United States
      declined significantly between 2000 and 2012. An increase in educational
      attainment was associated with some of the decline in dementia prevalence, but
      the full set of social, behavioral, and medical factors contributing to the
      decline is still uncertain. Continued monitoring of trends in dementia incidence
      and prevalence will be important for better gauging the full future societal
      impact of dementia as the number of older adults increases in the decades ahead.

PMID- 27893045
TI  - Association of 3 Different Antihypertensive Medications With Hip and Pelvic
      Fracture Risk in Older Adults: Secondary Analysis of a Randomized Clinical Trial.
AB  - Importance: On the basis of observational studies, the use of thiazide diuretics
      for the treatment of hypertension is associated with reduced fracture risk
      compared with nonuse. Data from randomized clinical trials are lacking.
      Objective: To examine whether the use of thiazide diuretics for the treatment of
      hypertension is associated with reduced fracture risk compared with nonuse.
      Design, Setting, and Participants: Using Veterans Affairs and Medicare claims
      data, this study examined hip and pelvic fracture hospitalizations in
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      participants randomized to first-step therapy with a thiazide-type diuretic
      (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an
      angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from
      February 1994 to January 1998; in-trial follow-up ended in March 2002. The mean
      follow-up was 4.9 years. Posttrial follow-up was conducted through the end of
      2006, using passive surveillance via national databases. For this secondary
      analysis, which used an intention-to-treat approach, data were analyzed from
      February 1, 1994, through December 31, 2006. Main Outcomes and Measures: Hip and
      pelvic fracture hospitalizations. Results: A total of 22 180 participants (mean
      [SD] age, 70.4 [6.7] years; 43.0% female; and 49.9% white non-Hispanic, 31.2%
      African American, and 19.1% other ethnic groups) were followed for up to 8 years
      (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16
      622 participants for whom claims data were available were followed for up to 5
      additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial,
      338 fractures occurred. Participants randomized to receive chlorthalidone vs
      amlodipine or lisinopril had a lower risk of fracture on adjusted analyses
      (hazards ratio [HR], 0.79; 95% CI, 0.63-0.98; P = .04). Risk of fracture was
      significantly lower in participants randomized to receive chlorthalidone vs
      lisinopril (HR, 0.75; 95% CI, 0.58-0.98; P = .04) but not significantly different
      compared with those randomized to receive amlodipine (HR, 0.82; 95% CI, 0.63
      1.08; P = .17). During the entire trial and posttrial period of follow-up, the
      cumulative incidence of fractures was nonsignificantly lower in participants
      randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87; 95%
      CI, 0.74-1.03; P = .10) and vs each medication separately. In sensitivity
      analyses, when 1 year after randomization was used as the baseline (to allow for
      the effects of medications on bone to take effect), similar results were obtained
      for in-trial and in-trial plus posttrial follow-up. Conclusions and Relevance:
      These findings from a large randomized clinical trial provide evidence of a
      beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic
      fracture risk compared with treatment with other antihypertensive medications.
      Trial Registration: clinicaltrials.gov Identifier: NCT00000542.

PMID- 27893044
TI  - Failure of the Porcine Ascending Aorta: Multidirectional Experiments and a
      Unifying Microstructural Model.
AB  - The ascending thoracic aorta is poorly understood mechanically, especially its
      risk of dissection. To make better predictions of dissection risk, more
      information about the multidimensional failure behavior of the tissue is needed,
      and this information must be incorporated into an appropriate
      theoretical/computational model. Toward the creation of such a model, uniaxial,
      equibiaxial, peel, and shear lap tests were performed on healthy porcine
      ascending aorta samples. Uniaxial and equibiaxial tests showed anisotropy with
      greater stiffness and strength in the circumferential direction. Shear lap tests
      showed catastrophic failure at shear stresses (150-200 kPa) much lower than
      uniaxial tests (750-2500 kPa), consistent with the low peel tension (~60 mN/mm).
      A novel multiscale computational model, including both prefailure and failure
      mechanics of the aorta, was developed. The microstructural part of the model
      included contributions from a collagen-reinforced elastin sheet and interlamellar
      connections representing fibrillin and smooth muscle. Components were represented
      as nonlinear fibers that failed at a critical stretch. Multiscale simulations of
      the different experiments were performed, and the model, appropriately specified,
      agreed well with all experimental data, representing a uniquely complete
      structure-based description of aorta mechanics. In addition, our experiments and
      model demonstrate the very low strength of the aorta in radial shear, suggesting
      an important possible mechanism for aortic dissection.

PMID- 27893046
TI  - Two vs Three Doses of Human Papillomavirus Vaccine: New Policy for the Second
      Decade of the Vaccination Program.

PMID- 27893047
TI  - The Road Ahead for Personalized Firearms.

PMID- 27893048
TI  - Dark Retinal Lesion in a Young Asymptomatic Man.

PMID- 27893050
TI  - When Does High Risk for Stroke Become Low Risk After Atrial Fibrillation
      Ablation?

PMID- 27893049
TI  - A Novel Approach to Assess the In Situ Versus Ex Vivo Mechanical Behaviors of the
      Coronary Artery.
AB  - Ex vivo mechanical testing has provided tremendous insight toward prediction of
      the in vivo mechanical behavior and local mechanical environment of the arterial
      wall; however, the role of perivascular support on the local mechanical behavior
      of arteries is not well understood. Here, we present a novel approach for
      quantifying the impact of the perivascular support on arterial mechanics using
      intravascular ultrasound (IVUS) on cadaveric porcine hearts. We performed
      pressure-diameter tests (n = 5) on the left anterior descending coronary arteries
      (LADCAs) in situ while embedded in their native perivascular environment using
      IVUS imaging and after removal of the perivascular support of the artery. We then
      performed standard cylindrical biaxial testing on these vessels ex vivo and
      compared the results. Removal of the perivascular support resulted in an upward
      shift of the pressure-diameter curve. Ex vivo testing, however, showed
      significantly lower circumferential compliance compared to the in situ
      configuration. On a second set of arteries, local axial stretch ratios were
      quantified (n = 5) along the length of the arteries. The average in situ axial
      stretch ratio was 1.28 +/- 0.16; however, local axial stretch ratios showed
      significant variability, ranging from 1.01 to 1.70. Taken together, the data
      suggest that both the perivascular loading and the axial tethering have an
      important role in arterial mechanics. Combining nondestructive testing using IVUS
      with traditional ex vivo cylindrical biaxial testing yields a more comprehensive
      assessment of the mechanical behavior of arteries.

PMID- 27893052
TI  - Errors in Reported Numbers in Table 1.

PMID- 27893051
TI  - Study of Cholesterol Repletion Effect on Nanomechanical Properties of Human
      Umbilical Vein Endothelial Cell Via Rapid Broadband Atomic Force Microscopy.
AB  - Abnormalities of blood cholesterol concentration are associated with increased
      risks for vascular disease, especially heart attacks and strokes. As one of the
      main lipid components of plasma membrane in all mammalian cells, cholesterol has
      a major impact on the mechanical properties of the membrane of endothelial cells.
      Although the effect of cholesterol depletion on cell mechanical properties has
      been studied, no results yet have been reported on quantitative investigation of
      cholesterol repletion effect. In this study, the cholesterol repletion effect on
      the nanomechanical properties of human umbilical vein endothelial cell (EA.hy926)
      was studied using a control-based atomic force microscope (AFM) nanomechanical
      measurement protocol. The viscoelasticity of EA.hy926 cells were measured over a
      large frequency range (0.1-100 Hz) using both constant-rate excitation force with
      different loading rates and a broadband excitation force. The viscoelasticity
      oscillation of the cell membranes under the cholesterol effect was also monitored
      in real-time. The experiment results showed that under the effect of cholesterol
      repletion, both the Young's modulus and the complex modulus of EA.hy926 cell were
      increased over 30%, respectively, and moreover, the amplitudes of both the
      elasticity oscillation and the viscosity oscillation at a period of around 200 s
      were increased over 70%, respectively. Therefore, this work is among the first to
      investigate the mechanical properties, particularly, the broadband
      viscoelasticity variations of EA.hy926 cells under cholesterol repletion
      treatment. The results revealed that cholesterol repletion may reinforce the
      coupling of F-actin to plasma membrane by increasing actin stability, and the
      cholesterol might have modified the submembrane cytoskeletal organization of
      EA.hy926 cell by causing the involvement of the motor protein nonmuscle myosin
      II.

PMID- 27893053
TI  - Appropriate Use of High-Sensitivity Cardiac Troponin Levels in Patients With
      Suspected Acute Myocardial Infarction.

PMID- 27893054
TI  - Outcomes and Temporal Trends of Inpatient Percutaneous Coronary Intervention at
      Centers With and Without On-site Cardiac Surgery in the United States.
AB  - Importance: There are concerns whether percutaneous coronary intervention (PCI)
      at centers without on-site cardiac surgery is safe outside of a tightly regulated
      research environment. Objective: To analyze the outcomes and temporal trends of
      inpatient PCI at centers without on-site cardiac surgery in an unselected and
      nationally representative population of the United States. Design, Setting, and
      Participants: A national inpatient sample (N = 6 912 232) was used to identify
      patients who underwent inpatient PCI in the United States from January 1, 2003,
      to December 31, 2012. Hospitals that performed 1 or more coronary artery bypass
      graft surgeries in a given calendar year were classified as centers with on-site
      cardiac surgery, and weighted sampling of all inpatient hospitalizations was
      performed. Data analysis was performed from February to May 2016. Exposures:
      Inpatient PCI. Main Outcomes and Measures: In-hospital mortality. Results: Of the
      6 912 232 inpatient PCIs performed, 2 336 334 patients (33.8%) were women and 4
      575 898 (66.2%) were men; their mean (SD) age was 64.5 (12.3) years. Of these
      PCIs, 396 741 (5.7%) were conducted at centers without on-site cardiac surgery.
      The rate of in-hospital mortality was significantly lower at centers with on-site
      cardiac surgery compared with centers without on-site cardiac surgery (1.4% vs
      1.9%; unadjusted odds ratio [OR], 0.74; 95% CI, 0.72-0.75). After adjustment,
      there was no significant difference in in-hospital mortality between centers with
      and without on-site cardiac surgery (OR, 1.01; 95% CI, 0.98-1.03; P = .62) for
      acute coronary syndromes and elective procedures requiring inpatient
      hospitalization. In addition, there were no significant differences in the risk
      adjusted, in-hospital mortality between the 2 groups in prespecified subgroups
      after adjusting for multiple comparisons, including ST-elevation myocardial
      infarction (OR, 0.99; 95% CI, 0.96-1.03; P = .65), non-ST-elevation acute
      coronary syndrome (OR, 0.99; 95% CI, 0.93-1.05; P = .66), and elective PCI (OR,
      0.93; 95% CI, 0.84-1.03; P = .17). There was a significant increase in the
      proportion of PCIs at centers without on-site cardiac surgery within the study
      period (from 1.8% to 12.7%; P < .001 for trend by Cochrane-Armitage test)
      reflected across all the indications. Conclusions and Relevance: There was a 7
      fold increase in the proportion of PCIs at centers without on-site cardiac
      surgery from 2003 to 2012 in the United States, with the adjusted in-hospital
      mortality after inpatient PCI being similar at centers with and without on-site
      cardiac surgery. These data provide evidence that PCI at centers without on-site
      cardiac surgery may be safe in the modern era.

PMID- 27893056
TI  - Percutaneous Coronary Intervention Without On-site Cardiac Surgery: It's Trendy,
      but Is It Right?

PMID- 27893055
TI  - Assessment of Use vs Discontinuation of Oral Anticoagulation After Pulmonary Vein
      Isolation in Patients With Atrial Fibrillation.
AB  - Importance: Pulmonary vein isolation (PVI) is a recommended treatment for
      patients with atrial fibrillation, but it is unclear whether it results in a
      lower risk of stroke. Objectives: To investigate the proportion of patients
      discontinuing anticoagulation treatment after PVI in association with the CHA2DS2
      VASc (congestive heart failure, hypertension, age >=75 years [doubled], diabetes,
      stroke [doubled], vascular disease, age 65-74 years, sex category [female])
      score, identify factors predicting stroke after PVI, and explore the risk of
      cardiovascular events after PVI in patients with and without guideline
      recommended anticoagulation treatment. Design, Setting, and Participants: A
      retrospective cohort study was conducted using Swedish national health registries
      from January 1, 2006, to December 31, 2012, with a mean-follow up of 2.6 years. A
      total of 1585 patients with atrial fibrillation undergoing PVI from the Swedish
      Catheter Ablation Register were included, with information about exposure to
      warfarin in the national quality register Auricula. Data analysis was performed
      from January 1, 2015, to April 30, 2016. Exposures: Warfarin treatment. Main
      Outcomes and Measures: Ischemic stroke, intracranial hemorrhage, and death.
      Results: In this cohort of 1585 patients, 73.0% were male, the mean (SD) age was
      59.0 (9.4) years, and the mean (SD) CHA2DS2-VASc score was 1.5 (1.4). Of the 1585
      patients, 1175 were followed up for more than 1 year after PVI. Of these, 360
      (30.6%) discontinued warfarin treatment during the first year. In patients with a
      CHA2DS2-VASc score of 2 or more, patients discontinuing warfarin treatment had a
      higher rate of ischemic stroke (5 events in 312 years at risk [1.6% per year])
      compared with those continuing warfarin treatment (4 events in 1192 years at risk
      [0.3% per year]) (P = .046). Patients with a CHA2DS2-VASc score of 2 or more or
      those who had previously experienced an ischemic stroke displayed a higher risk
      of stroke if warfarin treatment was discontinued (hazard ratio, 4.6; 95% CI, 1.2
      17.2; P = .02 and hazard ratio, 13.7; 95% CI, 2.0-91.9; P = .007, respectively).
      Conclusions and Relevance: These findings indicate that discontinuation of
      warfarin treatment after PVI is not safe in high-risk patients, especially those
      who have previously experienced an ischemic stroke.

PMID- 27893057
TI  - Appropriate Use of High-Sensitivity Cardiac Troponin Levels in Patients With
      Suspected Acute Myocardial Infarction-Reply.

PMID- 27893058
TI  - Lymph Node Biopsy in Patients With Papillary Thyroid Cancer-Reply.

PMID- 27893059
TI  - The Localized Hemodynamics of Drug-Eluting Stents Are Not Improved by the
      Presence of Magnetic Struts.
AB  - The feasibility of implementing magnetic struts into drug-eluting stents (DESs)
      to mitigate the adverse hemodynamics which precipitate stent thrombosis is
      examined. These adverse hemodynamics include platelet-activating high wall shear
      stresses (WSS) and endothelial dysfunction-inducing low wall shear stresses. By
      magnetizing the stent struts, two forces are induced on the surrounding blood:
      (1) magnetization forces which reorient red blood cells to align with the
      magnetic field and (2) Lorentz forces which oppose the motion of the conducting
      fluid. The aim of this study was to investigate whether these forces can be used
      to locally alter blood flow in a manner that alleviates the thrombogenicity of
      stented vessels. Two-dimensional steady-state computational fluid dynamics (CFD)
      simulations were used to numerically model blood flow over a single magnetic drug
      eluting stent strut with a square cross section. The effects of magnet
      orientation and magnetic flux density on the hemodynamics of the stented vessel
      were elucidated in vessels transporting oxygenated and deoxygenated blood. The
      simulations are compared in terms of the size of separated flow regions. The
      results indicate that unrealistically strong magnets would be required to achieve
      even modest hemodynamic improvements and that the magnetic strut concept is ill
      suited to mitigate stent thrombosis.

PMID- 27893061
TI  - Miscalculation and Errors in Numbers Reported in Table.

PMID- 27893060
TI  - Association Between Allergen Exposure in Inner-City Schools and Asthma Morbidity
      Among Students.
AB  - Importance: Home aeroallergen exposure is associated with increased asthma
      morbidity in children, yet little is known about the contribution of school
      aeroallergen exposures to such morbidity. Objective: To evaluate the effect of
      school-specific aeroallergen exposures on asthma morbidity among students,
      adjusting for home exposures. Design, Setting, and Participants: The School Inner
      City Asthma Study was a prospective cohort study evaluating 284 students aged 4
      to 13 years with asthma who were enrolled from 37 inner-city elementary schools
      in the northeastern United States between March 1, 2008, and August 31, 2013.
      Enrolled students underwent baseline clinical evaluations before the school year
      started and were then observed clinically for 1 year. During that same school
      year, classroom and home dust samples linked to the students were collected and
      analyzed for common indoor aeroallergens. Associations between school
      aeroallergen exposure and asthma outcomes during the school year were assessed,
      adjusting for home exposures. Exposures: Indoor aeroallergens, including rat,
      mouse, cockroach, cat, dog, and dust mites, measured in dust samples collected
      from inner-city schools. Main Outcomes and Measures: The primary outcome was
      maximum days in the past 2 weeks with asthma symptoms. Secondary outcomes
      included well-established markers of asthma morbidity, including asthma
      associated health care use and lung function, measured by forced expiratory
      volume in 1 second. Results: Among 284 students (median age, 8 years
      [interquartile range, 6-9 years]; 148 boys and 136 girls), exposure to mouse
      allergen was detected in 441 (99.5%) of 443 school dust samples, cat allergen in
      420 samples (94.8%), and dog allergen in 366 samples (82.6%). Levels of mouse
      allergen in schools were significantly higher than in students' homes (median
      settled dust level, 0.90 vs 0.14 ug/g; P < .001). Exposure to higher levels of
      mouse allergen in school (comparing 75th with 25th percentile) was associated
      with increased odds of having an asthma symptom day (odds ratio, 1.27; 95% CI,
      1.05-1.54; P = .02) and 4.0 percentage points lower predicted forced expiratory
      volume in 1 second (95% CI, -6.6 to -1.5; P = .002). This effect was independent
      of allergic sensitization. None of the other indoor aeroallergens were associated
      with worsening asthma outcomes. Conclusions and Relevance: In this study of inner
      city students with asthma, exposure to mouse allergen in schools was associated
      with increased asthma symptoms and decreased lung function. These findings
      demonstrate that the school environment is an important contributor to childhood
      asthma morbidity. Future school-based environmental interventions may be
      beneficial for this important public health problem.

PMID- 27893062
TI  - A Reporting Tool for Practice Guidelines in Health Care: The RIGHT Statement.
AB  - The quality of reporting practice guidelines is often poor, and there is no
      widely accepted guidance or standards for such reporting in health care. The
      international RIGHT (Reporting Items for practice Guidelines in HealThcare)
      Working Group was established to address this gap. The group followed an existing
      framework for developing guidelines for health research reporting and the EQUATOR
      (Enhancing the QUAlity and Transparency Of health Research) Network approach. It
      developed a checklist and an explanation and elaboration statement. The RIGHT
      checklist includes 22 items that are considered essential for good reporting of
      practice guidelines: basic information (items 1 to 4), background (items 5 to 9),
      evidence (items 10 to 12), recommendations (items 13 to 15), review and quality
      assurance (items 16 and 17), funding and declaration and management of interests
      (items 18 and 19), and other information (items 20 to 22). The RIGHT checklist
      can assist developers in reporting guidelines, support journal editors and peer
      reviewers when considering guideline reports, and help health care practitioners
      understand and implement a guideline.

PMID- 27893063
TI  - Assessment of the Psychometric Properties of a Questionnaire Assessing Patient
      Reported Outcomes With Laser In Situ Keratomileusis (PROWL).
AB  - Importance: Patient-reported outcome (PRO) measures for laser in situ
      keratomileusis (LASIK) are needed. Objective: To develop PRO measures to assess
      satisfaction, eye-related symptoms, and their effect on functioning and well
      being following LASIK based on patient and expert input. Design, Setting, and
      Participants: The Patient-Reported Outcomes With LASIK (PROWL) studies were
      prospective observational studies of patients undergoing LASIK surgery for
      myopia, hyperopia, or astigmatism. PROWL-1 was a single-center study of active
      duty US Navy personnel and PROWL-2 was a 5-center study of civilians. PROWL-1
      enrolled 262 active-duty service personnel and PROWL-2 enrolled 312 civilians 21
      years or older who spoke English; 241 individuals in PROWL-1 and 280 in PROWL-2
      completed a baseline questionnaire before surgery. The analytic sample included
      those also completing 1 or more follow-up questionnaires: 240 (99.6%) of those in
      PROWL-1 and 271 (94.4%) of those in PROWL-2. Questionnaires were self
      administered through the internet preoperatively and at 1 and 3 months
      postoperatively in both studies and at 6 months postoperatively in PROWL-1. PROWL
      1 began in August 2011 and was completed May 30, 2014; PROWL-2 began in July 2012
      and was completed June 27, 2014. Data were analyzed from June 28, 2014, to
      October 24, 2016. Main Outcomes and Measures: Scales assessing visual symptoms
      (double images, glare, halos, and starbursts), dry eye symptoms, satisfaction
      with vision, and satisfaction with LASIK surgery. Items from the National Eye
      Institute (NEI) Refractive Error Quality of Life Instrument (NEI-RQL-42), NEI
      Visual Function Questionnaire (NEI-VFQ), and the Ocular Surface Disease Index
      (OSDI) were included. All scales are scored on a 0 to 100 possible range.
      Construct validity and responsiveness to change were evaluated (comparing scores
      before and after surgery). Results: The median age of the 240-person PROWL-1
      analytic sample was 27 years (range, 21-52 years); 49 were women (20.4%). The
      median age of the 271-person PROWL-2 analytic sample was 30 years (range, 21-57
      years); 147 were women (54.2%). Internal consistency reliabilities for the 4
      visual symptom scales ranged from 0.96 to 0.98 in PROWL-1 and from 0.95 to 0.97
      in PROWL-2. The median (interquartile range) test-retest intraclass correlation
      was 0.69 (0.57-0.79) and 0.76 (0.68-0.84) in PROWL-1 and PROWL-2, respectively.
      Product-moment correlations of satisfaction with surgery with visual symptom
      scales at follow-up evaluations ranged from r = 0.24 to r = 0.49. Measures
      improved from baseline to follow-up, with effect sizes of 0.14 to 1.98, but
      scores on the NEI-RQL-42 glare scale worsened at the 1-month follow-up. Hours of
      work did not change significantly from baseline to 1-month follow-up, with the
      mean number (mean [SD] difference) in PROWL-1 of 41.7 vs 40.9 hours (-0.8 [18.7])
      and in PROWL-2 of 38.8 vs 38.2 hours (-0.6 [17.1]). Conclusions and Relevance:
      The results of these studies support the reliability and validity of visual
      symptom scales to evaluate the effects of LASIK surgery in future studies.

PMID- 27893065
TI  - Histology and Biaxial Mechanical Behavior of Abdominal Aortic Aneurysm Tissue
      Samples.
AB  - Abdominal aortic aneurysms (AAAs) represent permanent, localized dilations of the
      abdominal aorta that can be life-threatening if progressing to rupture.
      Evaluation of risk of rupture depends on understanding the mechanical behavior of
      patient AAA walls. In this project, a series of patient AAA wall tissue samples
      have been evaluated through a combined anamnestic, mechanical, and
      histopathologic approach. Mechanical properties of the samples have been
      characterized using a novel, strain-controlled, planar biaxial testing protocol
      emulating the in vivo deformation of the aorta. Histologically, the tissue
      ultrastructure was highly disrupted. All samples showed pronounced mechanical
      stiffening with stretch and were notably anisotropic, with greater stiffness in
      the circumferential than the axial direction. However, there were significant
      intrapatient variations in wall stiffness and stress. In biaxial tests in which
      the longitudinal stretch was held constant at 1.1 as the circumferential stretch
      was extended to 1.1, the maximum average circumferential stress was 330 +/- 70
      kPa, while the maximum average axial stress was 190 +/- 30 kPa. A constitutive
      model considering the wall as anisotropic with two preferred directions fit the
      measured data well. No statistically significant differences in tissue mechanical
      properties were found based on patient gender, age, maximum bulge diameter,
      height, weight, body mass index, or smoking history. Although a larger patient
      cohort is merited to confirm these conclusions, the project provides new insight
      into the relationships between patient natural history, histopathology, and
      mechanical behavior that may be useful in the development of accurate methods for
      rupture risk evaluation.

PMID- 27893064
TI  - Effect of Increased Enteral Protein Intake on Growth in Human Milk-Fed Preterm
      Infants: A Randomized Clinical Trial.
AB  - Importance: Protein, supplied in currently available commercial fortifiers, may
      be inadequate to meet the requirements of very preterm infants; in addition,
      intraindividual and interindividual variability of human milk protein and energy
      content potentially contribute to unsatisfactory early postnatal growth.
      Objective: To determine effects on growth of different levels of enteral protein
      supplementation in predominantly human milk-fed preterm infants. Design, Setting,
      and Participants: This randomized clinical and partially blinded single-center
      trial was conducted in a neonatal tertiary referral center in Germany. Sixty
      preterm infants (gestation <32 weeks and weight <1500 g at birth) were recruited
      from October 2012 to October 2014 and included 35% of 173 eligible infants.
      Median (interquartile range [IQR]) gestational age at birth was 29.9 (28.7-31.2)
      weeks. All analyses were conducted in an intention-to-treat population.
      Interventions: Infants were randomly assigned to either a lower-protein (adding 1
      g of bovine protein/100 mL of breast milk through a commercial human milk
      fortifier; n = 30) or a higher-protein group at a median (IQR) postnatal age of 7
      (6-8) days. The higher-protein group (n = 30) received either standardized higher
      protein supplementation (study fortifier adding 1.8 g of bovine protein/100 mL of
      breast milk [n = 15]) or individualized high-protein supplementation based on
      protein and fat content of administered breast milk (n = 15). Study interventions
      were continued for a median (IQR) of 41 (30-57) days and until definite discharge
      planning. Main Outcomes and Measures: Primary outcome was weight gain (g/kg/d)
      from birth to the end of intervention. Results: Sixty preterm infants (gestation
      <32 weeks and weight <1500 g at birth), 33 girls, were recruited from October
      2012 to October 2014 and included 35% of 173 eligible infants. Median (IQR)
      gestational age at birth was 29.9 (28.7-31.2) weeks. Demographic characteristics
      and hospital courses were similar in both groups, and birth weights ranged from
      580 to 1495 g in the lower-protein group and 490 to 1470 g in the higher-protein
      group. Weight gain was similar in the lower- and higher-protein groups: mean (95%
      CI), 16.3 g/kg/d (15.4-17.1 g/kg/d) in the lower-protein group vs 16.0 g/kg/d
      (15.1-16.9 g/kg/d) in the higher-protein group) (P = .70), despite an increase in
      actual protein intake by 0.6 g/kg/d (0.4-0.7 g/kg/d) (P < .001). Head
      circumference and lower leg longitudinal growth were also similar, as was the
      proportion of cumulative total enteral feeding volume provided as breast milk:
      median (IQR) proportion of breast milk, 92% (79%-98%) in the lower-protein group
      vs 94% (62%-99%) in the higher-protein group (P = .89). Conclusions and
      Relevance: An increase in protein intake by 0.6 g/kg/d to a mean intake of 4.3
      g/kg/d did not further enhance growth of very preterm infants with a median birth
      weight of 1200 g, who achieved near-fetal growth rates. This might point to a
      ceiling effect for enteral protein intake with respect to its influence on
      growth. Trial Registration: clinicaltrials.gov Identifier: NCT01773902.

PMID- 27893066
TI  - Symptoms and Satisfaction of Patients in the Patient-Reported Outcomes With Laser
      In Situ Keratomileusis (PROWL) Studies.
AB  - Importance: Patient-reported outcomes should be collected using validated
      questionnaires prior to and following laser in situ keratomileusis (LASIK)
      surgery. Objective: To report the frequency of patient-reported visual symptoms,
      dry eye symptoms, satisfaction with vision, and satisfaction with LASIK surgery
      in the Patient-Reported Outcomes With LASIK (PROWL) studies. Design, Setting, and
      Participants: The PROWL-1 and PROWL-2 studies were prospective, observational
      studies conducted from September 13, 2011, to June 27, 2014. The PROWL-1 study
      was a single-military center study of 262 active-duty Navy personnel 21 to 52
      years of age. The PROWL-2 study was a study of 312 civilians 21 to 57 years of
      age conducted at 5 private practice and academic centers. The LASIK surgery and
      the postoperative care were performed based on the usual practice and clinical
      judgment at the site. Participants completed a self-administered, web-based
      questionnaire, preoperatively and postoperatively at 1 and 3 months (the PROWL-1
      and -2 studies) and at 6 months (the PROWL-2 study). Exposures: Participants
      underwent LASIK surgery for myopia, hyperopia, and/or astigmatism. Main Outcomes
      and Measures: Visual symptoms (double images, glare, halos, and/or starbursts),
      dry eye symptoms, participant satisfaction (with vision and LASIK surgery), and
      clinical measures (visual acuity, refractive error, and slitlamp and posterior
      segment eye examination findings) were assessed preoperatively and at 1, 3, and 6
      months postoperatively. Results: A total of 262 participants were enrolled in the
      PROWL-1 study (mean [SD] age, 29.1 [6.1] years), and a total of 312 participants
      were enrolled in the PROWL-2 study (mean [SD] age, 31.5 [7.3] years). Visual
      symptoms and dissatisfaction with vision were common preoperatively. Overall, the
      prevalence of visual symptoms and dry eye symptoms decreased, although a
      substantial percentage of participants reported new visual symptoms after surgery
      (43% [95% CI, 31%-55%] from the PROWL-1 study and 46% [95% CI, 33%-58%] from the
      PROWL-2 study at 3 months). The percentages of participants in the PROWL-1 study
      with normal Ocular Surface Disease Index scores were 55% (95% CI, 48%-61%) at
      baseline, 66% (95% CI, 59%-72%) at 3 months, and 73% (95% CI, 67%-79%) at 6
      months. The percentages of participants in the PROWL-2 study with normal Ocular
      Surface Disease Index scores were 44% (95% CI, 38%-50%) at baseline and 65% (95%
      CI, 59%-71%) at 3 months. Of those participants who had normal scores at baseline
      in both the PROWL-1 and -2 studies, about 28% (95% CI, 19%-37%) had mild,
      moderate, or severe dry eye symptoms at 3 months. While most participants were
      satisfied, the rates of dissatisfaction with vision ranged from 1% (95% CI, 0%
      4%) to 4% (95% CI, 2%-7%), and the rates of dissatisfaction with surgery ranged
      from 1% (95% CI, 0%-4%) to 2% (95% CI, 1%-5%). Conclusions and Relevance: The
      systematic administration of a questionnaire to patients who have undergone LASIK
      surgery is a new approach to assess symptoms and satisfaction. Our findings
      support the need for adequate counseling about the possibility of developing new
      symptoms after LASIK surgery.

PMID- 27893067
TI  - Prioritizing Pediatric Drug Research Using Population-Level Health Data.

PMID- 27893069
TI  - New Medical and Surgical Insights Into Neonatal Necrotizing Enterocolitis: A
      Review.
AB  - Importance: Necrotizing enterocolitis (NEC) has long remained a significant cause
      of morbidity and mortality in neonatal intensive care units. While the mainstay
      of treatment for this devastating condition remains largely supportive, research
      efforts continue to be directed toward understanding pathophysiology as well as
      how best to approach surgical management when indicated. Observations: In this
      review, we first examine recent medical observations, including overviews on the
      microbiome and a brief review of the use of probiotics. Next, we discuss the use
      of biomarkers and how clinicians may be able to use them in the future to predict
      the course of disease and, perhaps, the need for surgical intervention. We then
      provide an overview on the use of exclusive human milk feeding and the utility of
      this approach in preventing NEC. Finally, we discuss recent developments in the
      surgical management of NEC, beginning with indications for surgery and following
      with a section on technical surgical considerations, including peritoneal drain
      vs laparotomy. The review concludes with outcomes from infants with surgically
      treated NEC. Conclusions and Relevance: Although medical treatment options for
      NEC are largely unchanged, understanding of the disease continues to evolve. As
      new research methods are developed, NEC pathophysiology can be more completely
      understood. In time, it is hoped that data from ongoing and planned clinical
      trials will allow us to routinely add targeted preventive measures in addition to
      human milk, such as prebiotics and probiotics, to the management of high-risk
      infants. In addition, the discovery of novel biomarkers may not only prove useful
      in predicting severity of illness but also will hopefully allow for
      identification of the disease prior to onset of clinical signs. Finally,
      continued investigation into optimizing surgical outcomes is essential in this
      population of infants, many of whom require long-term parenteral therapy and
      intestinal rehabilitation.

PMID- 27893068
TI  - Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and
      Boys vs a 3-Dose Regimen in Women.
AB  - Importance: Human papillomavirus (HPV) infections cause anogenital cancers and
      warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of
      HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for
      90% of genital warts. Objective: To determine whether HPV type-specific antibody
      responses would be noninferior among girls and boys aged 9 to 14 years after
      receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and
      young women aged 16 to 26 years receiving 3 doses. Design, Setting, and
      Participants: Open-label, noninferiority, immunogenicity trial conducted at 52
      ambulatory care sites in 15 countries. The study was initiated on December 16,
      2013, with the last participant visit for this report on June 19, 2015. Five
      cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months
      apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n
      = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart
      (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n =
      301); and (5) a control group of adolescent girls and young women aged 16 to 26
      years to receive 3 doses over 6 months (n = 314). Interventions: Two doses of the
      9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered
      over 6 months. Main Outcomes and Measures: The primary end point was prespecified
      as the antibody response against each HPV type assessed 1 month after the last
      dose using a competitive immunoassay. Each of the three 2-dose regimens was
      compared with the standard 3-dose schedule in adolescent girls and young women
      using a noninferiority margin of 0.67 for the ratio of the antibody geometric
      mean titers. Results: Of the 1518 participants (753 girls [mean age, 11.4 years];
      451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean
      age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At
      4 weeks after the last dose, HPV antibody responses in girls and boys given 2
      doses were noninferior to HPV antibody responses in adolescent girls and young
      women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls
      and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the
      ratio of HPV antibody geometric mean titers at 1 month after the last dose across
      the 9 HPV subtypes ranged from 1.36 to infinity to 2.50 to infinity for girls who
      received 2 doses 6 months apart; from 1.37 to infinity to 2.55 to infinity for
      boys who received 2 doses 6 months apart; and from 1.61 to infinity to 5.36 to
      infinity for girls and boys who received 2 doses 12 months apart. Conclusions and
      Relevance: Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a
      9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after
      the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls
      and young women. Further research is needed to assess persistence of antibody
      responses and effects on clinical outcomes. Trial Registration:
      clinicaltrials.gov Identifier: NCT01984697.

PMID- 27893070
TI  - Contingent Valuation Analysis of an Otolaryngology and Ophthalmology Emergency
      Department: The Value of Acute Specialty Care.
AB  - Importance: Specialty emergency departments (EDs) provide a unique mechanism of
      health care delivery, but the value that they add to the medical system is not
      known. Evaluation of patient preferences to determine value can have a direct
      impact on resource allocation and direct-to-specialist care. Objective: To assess
      the feasibility of contingent valuation (CV) methodology using a willingness-to
      pay (WTP) survey to evaluate specialty emergency services, in the context of an
      ophthalmology- and otolaryngology-specific ED. Design, Setting, and Participants:
      Contingent valuation analysis of a standalone otolaryngology and ophthalmology
      ED. Participants were English-speaking adults presenting to a dedicated
      otolaryngology and ophthalmology ED. The WTP questions were assessed using a
      payment card format, with reference to an alternative modality of treatment (ie,
      general ED), and were analyzed with multivariate regression. Intervention:
      Validated WTP survey administered from October 14, 2014, through October 1, 2015.
      Main Outcomes and Measures: Sociodemographic data, level of distress, referral
      data, income, and WTP. Results: A total of 327 of 423 (77.3%) ED patients
      responded to the WTP survey, with 116 ophthalmology and 211 otolaryngology
      patients included (52.3% female; mean [range] age, 46 [18-90] years). The most
      common reason for seeking care at this facility was a reputation for specialty
      care for both ear, nose, and throat (80 [37.9%]) and ophthalmology (43 [37.1%]).
      Mean WTP for specialty-specific ED services was $377 for ophthalmology patients,
      and $321 for otolaryngology patients ($340 overall; 95% CI, $294 to $386),
      without significant difference between groups (absolute difference, $56; 95% CI,
      $-156 to $43). Self-reported level of distress was higher among ear, nose, and
      throat vs ophthalmology patients (absolute difference, 0.47 on a Likert scale of
      1-7; 95% CI, 0.10 to 0.84). Neither level of distress, income, nor demographic
      characteristics influenced WTP, but patients with higher estimates of total visit
      cost were more likely to have higher WTP (beta coefficient, 0.27; SE, 0.05;
      adjusted R2 = 0.17 for model). Conclusions and Relevance: Patients with eye and
      ear, nose, and throat complaints place a mean explicit value on specialty
      emergency services of $340 per visit, relative to general emergency care.
      Ultimately, CV data using WTP methodology are useful in valuing patient
      preferences in monetary terms and can help inform state-wide resource allocation
      and the availability of direct-to-specialist care.

PMID- 27893071
TI  - Small Steps Toward Asthma-Friendly School Environments.

PMID- 27893072
TI  - Lymph Node Biopsy in Patients With Papillary Thyroid Cancer.

PMID- 27893073
TI  - Association Between Severity of Obstructive Sleep Apnea and Number and Sites of
      Upper Airway Operations With Surgery Complications.
AB  - Importance: In patients with obstructive sleep apnea (OSA), operative risks
      depend on the severity of the underlying OSA and the invasiveness of the surgical
      procedure. Objective: To investigate the nature of the associations between the
      severity of OSA and the number and anatomical sites of upper airway operations
      with operative complications. Design, Setting, and Participants: This
      retrospective study included adult patients diagnosed with OSA (apnea-hypopnea
      index [AHI], >5) who underwent upper airway surgery at a single tertiary referral
      hospital between October 1, 2008, and October 1, 2015. Interventions: All
      patients underwent single or combination surgery on the nose, palatopharyngeal
      (tonsils, adenoids, and soft palate), and tongue base as a treatment of OSA. Main
      Outcomes and Measures: Pulmonary, surgical, and cardiovascular complications
      within the first 30 postoperative days were analyzed according to OSA severity
      and types of upper airway surgery. Logistic regression was used to assess the
      multivariable association of OSA, age, sex, body mass index, medical
      comorbidities, and types of upper airway surgery with short-term operative
      complications. Results: The study included 95 patients (87 males [91.6%]; 83 were
      Malay [87.4%]; mean [SD] age, 37.7 [1.6] years) with complete data and follow-up
      who underwent upper airway surgery to treat OSA. Patients with more severe OSA
      had greater body mass index (Cohen d, 0.27; 95% CI, -0.28 to 0.82), longer
      surgical time (Cohen d, 1.57; 95% CI, 0.95-2.15), and older age (Cohen d, 3.06;
      95% CI, 2.29-3.77). At least 1 operative complication occurred in 48 of 95
      patients (51%). In a multivariable model, the overall complication rate was
      increased with age and body mass index. Complication rates were not associated
      with AHI severity, type of procedure performed, and whether the surgery was
      single or combination surgery. Lowest oxygen desaturation (odds ratio, 1.03; 95%
      CI, 0.96-1.45; P = .04) and longest apnea duration (odds ratio, 1.03; 95% CI,
      0.99-1.08; P = .02) were polysomnographic variables that predict the short-term
      operative complications. Conclusions and Relevance: In patients with OSA
      undergoing upper airway surgery, the severity of OSA as assessed by AHI, and the
      sites and numbers of concurrent operations performed were not associated with the
      rate of short-term operative complications.

PMID- 27893077
TI  - A general account of peripheral encoding also predicts scene perception
      performance.
AB  - People are good at rapidly extracting the "gist" of a scene at a glance, meaning
      with a single fixation. It is generally presumed that this performance cannot be
      mediated by the same encoding that underlies tasks such as visual search, for
      which researchers have suggested that selective attention may be necessary to
      bind features from multiple preattentively computed feature maps. This has led to
      the suggestion that scenes might be special, perhaps utilizing an unlimited
      capacity channel, perhaps due to brain regions dedicated to this processing. Here
      we test whether a single encoding might instead underlie all of these tasks. In
      our study, participants performed various navigation-relevant scene perception
      tasks while fixating photographs of outdoor scenes. Participants answered
      questions about scene category, spatial layout, geographic location, or the
      presence of objects. We then asked whether an encoding model previously shown to
      predict performance in crowded object recognition and visual search might also
      underlie the performance on those tasks. We show that this model does a
      reasonably good job of predicting performance on these scene tasks, suggesting
      that scene tasks may not be so special; they may rely on the same underlying
      encoding as search and crowded object recognition. We also demonstrate that a
      number of alternative "models" of the information available in the periphery also
      do a reasonable job of predicting performance at the scene tasks, suggesting that
      scene tasks alone may not be ideal for distinguishing between models.

PMID- 27893074
TI  - The Nurses' Health Study Takes Fresh Aim at Breast Cancer as It Heads Into Decade
      Five.

PMID- 27893078
TI  - Recent advances toward preclinical and clinical translation of photoacoustic
      tomography: a review.

PMID- 27893079
TI  - Endoscopic Repair of Tympanic Membrane Perforations : An Exercise of Acrobatic
      Dexterity or the Sign of the Beginning of a New Era in Otology?

PMID- 27893083
TI  - Cohesive Referencing Errors During Narrative Production as Clinical Evidence of
      Central Nervous System Abnormality in School-Aged Children With Fetal Alcohol
      Spectrum Disorders.
AB  - Purpose: Previous evidence suggests that cohesive referencing errors made during
      narratives may be a behavior that is revealing of underlying central nervous
      system abnormality in children with fetal alcohol spectrum disorders (FASD). The
      current research extends this evidence. Method: Retrospective analysis of
      narrative and clinical data from 152 children (ages 6 to 14), 72 of whom had
      confirmed FASD, was used. Narrative analysis was conducted blind to diagnostic
      status, age, or gender. Group performance was compared. The associations between
      measures of cohesive referencing and clinically gathered indices of the degree of
      central nervous system abnormality were examined. Results: Results show clear
      associations between elevated rates of cohesive referencing errors and central
      nervous system abnormality. Elevated error rates were more common in children
      with FASD than those without, and prevalence increased predictably across groups
      with more severe central nervous system abnormality. Risk is particularly
      elevated for those with microcephaly or a diagnosis of fetal alcohol syndrome.
      Conclusion: Cohesive referencing errors during narrative are a viable behavioral
      marker of the kinds of central nervous system abnormality associated with
      prenatal alcohol exposure, having significant potential to become a valuable
      diagnostic and research tool.

PMID- 27893084
TI  - Feasibility of Clinical Endoscopy and Stroboscopy in Children With Bilateral
      Vocal Fold Lesions.
AB  - Purpose: The purpose of this study was to examine the utility of flexible and
      rigid endoscopy and stroboscopy for the identification of anatomical and
      physiological features in children with bilateral vocal fold lesions. The
      secondary purpose was to describe the age distribution of patients who could
      tolerate use of the different types of endoscopes. Method: This cross-sectional
      clinic-based study included 38 children (ages 5 to 12 years) diagnosed with
      bilateral vocal fold lesions via videoendoscopy. Vocal fold vibratory
      characteristics (e.g., mucosal wave) were rated by 4 clinicians by consensus.
      Results: Bilateral vocal fold lesions could be well described anatomically after
      visualization with both flexible and rigid endoscopes and were most commonly
      described as symmetrical and broad based. However, the clinicians' confidence in
      the accuracy of stroboscopy for rating vocal fold vibratory characteristics was
      limited for both flexible and rigid stroboscopes. Conclusions: Videoendoscopy was
      adequate for viewing and characterizing anatomical structures of bilateral vocal
      fold lesions in pediatric patients; however, vibratory characteristics were often
      not fully visualized with videostroboscopy. In view of the importance of
      visualizing vocal fold vibration in the differential diagnosis and treatment of
      vocal fold lesions, other imaging modalities, such as high-speed videoendoscopy,
      may provide more accurate descriptions of vocal fold vibratory characteristics in
      this population.

PMID- 27893080
TI  - Travel-Associated Zika Virus Disease Acquired in the Americas Through February
      2016: A GeoSentinel Analysis.
AB  - Background: Zika virus has spread rapidly in the Americas and has been imported
      into many nonendemic countries by travelers. Objective: To describe clinical
      manifestations and epidemiology of Zika virus disease in travelers exposed in the
      Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and
      tropical medicine clinics in 30 countries. Patients: Ill returned travelers with
      a confirmed, probable, or clinically suspected diagnosis of Zika virus disease
      seen between January 2013 and 29 February 2016. Measurements: Frequencies of
      demographic, trip, and clinical characteristics and complications. Results:
      Starting in May 2015, 93 cases of Zika virus disease were reported. Common
      symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine
      percent of patients were exposed in South America; 71% were diagnosed in Europe.
      Case status was established most commonly by polymerase chain reaction (PCR)
      testing of blood and less often by PCR testing of other body fluids or serology
      and plaque-reduction neutralization testing. Two patients developed Guillain
      Barre syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major
      fetal neurologic abnormalities, and intrauterine fetal death). Limitation:
      Surveillance data collected by specialized clinics may not be representative of
      all ill returned travelers, and denominator data are unavailable. Conclusion:
      These surveillance data help characterize the clinical manifestations and adverse
      outcomes of Zika virus disease among travelers infected in the Americas and show
      a need for global standardization of diagnostic testing. The serious fetal
      complications observed in this study highlight the importance of travel
      advisories and prevention measures for pregnant women and their partners.
      Travelers are sentinels for global Zika virus circulation and may facilitate
      further transmission. Primary Funding Source: Centers for Disease Control and
      Prevention, International Society of Travel Medicine, and Public Health Agency of
      Canada.

PMID- 27893085
TI  - Goodness and Accentedness Ratings of /hVt/ Tokens by Aware and Naive Listeners.
AB  - Purpose: This study compares goodness and accentedness ratings of speech tokens
      rated by listeners who are naive to and aware of speakers' native language
      backgrounds. Listener responses to open-ended questions regarding goodness and
      accentedness ratings are also examined. Method: Twenty-eight monolingual speakers
      of U.S. English served as listeners. Listeners were presented with 5 blocks of
      /hVt/ tokens. Each block represented a different vowel target and comprised
      correct and incorrect productions from English, Spanish, Korean, and Japanese
      speakers. Listeners rated goodness and accentedness using a 9-point Likert scale
      and explained their decision-making criteria when judging goodness versus
      accentedness. Results: There is a high positive correlation between goodness and
      accentedness. Both naive and aware listeners assigned poorer ratings when judging
      goodness compared with accentedness, but results varied on the basis of target
      accuracy. Aware listeners assigned better goodness and accentedness ratings
      compared with naive listeners. This difference was highly statistically
      significant. Both accentedness and goodness ratings are susceptible to listener
      bias. Conclusions: Goodness and accentedness are highly correlated yet distinct
      measures. Goodness is more reflective of target accuracy than is accentedness.
      Native English tokens were affected by listener bias to a greater extent than
      nonnative English tokens.

PMID- 27893086
TI  - The Composition of Early Vocabulary in Spanish Children With Down Syndrome and
      Their Peers With Typical Development.
AB  - Purpose: There are very few studies, and at present none in Spanish, on
      vocabulary composition in children with Down syndrome (DS). Nor has the topic
      been widely assessed in Spanish-speaking children with typical development (TD).
      This study analyzed the composition of early vocabularies in a large sample of
      Spanish-speaking children with DS and compared it with that of children with TD.
      Method: We studied 108 children with DS and 108 children with TD with mental ages
      between 8 and 29 months, matched for size of productive vocabulary and gender.
      The MacArthur-Bates Communicative Development Inventories (Fenson et al., 1993,
      2007), adapted to the language development profile of children with DS, were
      used. The categories examined were nouns, predicates, closed-class words, and
      social words. Results: The performance of children with DS was similar to that of
      children with TD with the same vocabulary size. The only significant difference
      was the larger production of nouns by children with DS. The trends of development
      in the different classes of words were also similar. Conclusions: The strategies
      used by children with DS to learn vocabulary may be similar to those used by
      children with TD in the first stages of language learning.

PMID- 27893088
TI  - Light-scattering gating and characterization of plasma microparticles.
AB  - Flow cytometry method (FCM) is widely used for analysis of cell-derived
      microparticles (MPs). Numerous efforts are currently aimed to standardize these
      measurements among different instruments. We push the FCM characterization of MPs
      to the limit based on rigorous simulation of measured signals. We measured
      forward- and side-scatter (FSC/SSC) signals and angle-resolved light-scattering
      profiles (LSPs) of polystyrene microspheres and MPs, including their aggregates,
      using a scanning flow cytometer (SFC). We used the Mie theory to (1) accurately
      evaluate instrument detection limits; (2) construct FSC/SSC gates for MPs in
      absolute scales of size and refractive index (RI); and (3) determine size and RI
      of individual spherical MPs. LSPs were used for advanced characterization,
      including differentiation of spherical and nonspherical particles. The proposed
      absolute FSC/SSC gating is naturally standardized for any FCM instrument, given
      the knowledge of its optical system and leads to instrument-independent analysis
      of MPs. The inverse Mie problem has a unique solution only for some regions of
      size and RI and uncertainties rapidly increase with decreasing size and RI. The
      developed methods are applicable to any flow cytometer, but are limited by
      assumption of particle sphericity. The latter can be relaxed only if additional
      signals, such as LSP, are measured.

PMID- 27893087
TI  - Targeting Functional Decline in Alzheimer Disease: A Randomized Trial.
AB  - Background: Alzheimer disease results in progressive functional decline, leading
      to loss of independence. Objective: To determine whether collaborative care plus
      2 years of home-based occupational therapy delays functional decline. Design:
      Randomized, controlled clinical trial. (ClinicalTrials.gov: NCT01314950).
      Setting: Urban public health system. Patients: 180 community-dwelling
      participants with Alzheimer disease and their informal caregivers. Intervention:
      All participants received collaborative care for dementia. Patients in the
      intervention group also received in-home occupational therapy delivered in 24
      sessions over 2 years. Measurements: The primary outcome measure was the
      Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale
      (ADCS ADL); performance-based measures included the Short Physical Performance
      Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM). Results: At
      baseline, clinical characteristics did not differ significantly between groups;
      the mean Mini-Mental State Examination score for both groups was 19 (SD, 7). The
      intervention group received a median of 18 home visits from the study
      occupational therapists. In both groups, ADCS ADL scores declined over 24 months.
      At the primary end point of 24 months, ADCS ADL scores did not differ between
      groups (mean difference, 2.34 [95% CI, -5.27 to 9.96]). We also could not
      definitively demonstrate between-group differences in mean SPPB or SPSM values.
      Limitation: The results of this trial are indeterminate and do not rule out
      potential clinically important effects of the intervention. Conclusion: The
      authors could not definitively demonstrate whether the addition of 2 years of in
      home occupational therapy to a collaborative care management model slowed the
      rate of functional decline among persons with Alzheimer disease. This trial
      underscores the burden undertaken by caregivers as they provide care for family
      members with Alzheimer disease and the difficulty in slowing functional decline.
      Primary Funding Source: National Institute on Aging.

PMID- 27893089
TI  - Photoacoustic mammography capable of simultaneously acquiring photoacoustic and
      ultrasound images.
AB  - We have constructed a prototype photoacoustic mammography system (PAM-02) capable
      of simultaneously acquiring photoacoustic (PA) and ultrasound (US) images. Each
      PA, US, and fused PA/US image can be acquired over a wide area of the breast
      using the scanning module of a US transducer, a PA detector, and optical prisms.
      The resolution of the PA images exhibits improvement from 2 to 1 mm compared to
      images acquired using our previous prototype. The maximum scan area of PAM-02 is
      90 mm along the horizontal axis and 150 mm along the vertical axis. In a phantom
      experiment, the available depth was at least 45 mm. A representative example of
      the application of the PAM-02 prototype in clinical research at Kyoto University
      is presented and shows S-factor images, which are considered an approximation
      parameter related to hemoglobin saturation of tumor-related blood vessels. We
      confirmed the applicability of the system for anatomical and biological research.

PMID- 27893091
TI  - Spatial probabilistic pulsatility model for enhancing photoplethysmographic
      imaging systems.
AB  - Photoplethysmographic imaging (PPGI) is a widefield noncontact biophotonic
      technology able to remotely monitor cardiovascular function over anatomical
      areas. Although spatial context can provide insight into physiologically relevant
      sampling locations, existing PPGI systems rely on coarse spatial averaging with
      no anatomical priors for assessing arterial pulsatility. Here, we developed a
      continuous probabilistic pulsatility model for importance-weighted blood pulse
      waveform extraction. Using a data-driven approach, the model was constructed
      using a 23 participant sample with a large demographic variability (11/12
      female/male, age 11 to 60 years, BMI 16.4 to 35.1??kg.m?2). Using time
      synchronized ground-truth blood pulse waveforms, spatial correlation priors were
      computed and projected into a coaligned importance-weighted Cartesian space. A
      modified Parzen-Rosenblatt kernel density estimation method was used to compute
      the continuous resolution-agnostic probabilistic pulsatility model. The model
      identified locations that consistently exhibited pulsatility across the sample.
      Blood pulse waveform signals extracted with the model exhibited significantly
      stronger temporal correlation (W=35,p<0.01) and spectral SNR (W=31,p<0.01)
      compared to uniform spatial averaging. Heart rate estimation was in strong
      agreement with true heart rate [r2=0.9619, error (?,?)=(0.52,1.69) bpm].

PMID- 27893090
TI  - Distinguishing tracheal and esophageal tissues with hyperspectral imaging and
      fiber-optic sensing.
AB  - During emergency medical situations, where the patient has an obstructed airway
      or necessitates respiratory support, endotracheal intubation (ETI) is the medical
      technique of placing a tube into the trachea in order to facilitate adequate
      ventilation of the lungs. Complications during ETI, such as repeated attempts,
      failed intubation, or accidental intubation of the esophagus, can lead to severe
      consequences or ultimately death. Consequently, a need exists for a feedback
      mechanism to aid providers in performing successful ETI. Our study examined the
      spectral reflectance properties of the tracheal and esophageal tissue to
      determine whether a unique spectral profile exists for either tissue for the
      purpose of detection. The study began by using a hyperspectral camera to image
      excised pig tissue samples exposed to white and UV light in order to capture the
      spectral reflectance properties with high fidelity. After identifying a unique
      spectral characteristic of the trachea that significantly differed from
      esophageal tissue, a follow-up investigation used a fiber optic probe to confirm
      the detectability and consistency of the different reflectance characteristics in
      a pig model. Our results characterize the unique and consistent spectral
      reflectance characteristic of tracheal tissue, thereby providing foundational
      support for exploiting spectral properties to detect the trachea during medical
      procedures.

PMID- 27893092
TI  - Global Patterns in Health Burden of Uncorrected Refractive Error.
AB  - Purpose: To evaluate the global patterns in health burden of uncorrected
      refractive error (URE) by year, age and sex, region, and socioeconomic status,
      using disability-adjusted life years (DALYs). Methods: Global, regional, or
      national DALY numbers, crude DALY rates, and age-standardized DALY rates caused
      by URE, by year, or age and sex, were obtained from the Global Burden of Disease
      Study 2013. Human development index (HDI) in 2013 as a national socioeconomic
      indicator was obtained from the Human Development Report. Kruskal-Wallis test and
      linear regression were performed to explore the association between age
      standardized DALY rates and HDI. Results: From 1990 to 2013, global DALY numbers
      caused by URE rose by 43.8%, crude rates remained relatively constant, and age
      standardized rates fell by 8.8%. Global DALY rates increased with age, and older
      females had higher DALY numbers and rates than males of the same age. Age
      standardized DALY rates in Eastern Mediterranean, South-East Asia, and Africa
      were higher than that at a global level. Multiple comparisons indicated higher
      age-standardized DALY rates in lower HDI countries. Age-standardized DALY rates
      were inversely related to HDI (standardized beta = -0.616, P < 0.001).
      Conclusions: The global health of URE is improving but crude DALY rates are
      keeping constant, implying that health progress does not mean fewer demands of
      refractive services. Worldwide, older age, female sex, and lower socioeconomic
      status are associated with higher URE burden. The findings of this study may
      raise public awareness of the global URE burden and are important for health
      policy making.

PMID- 27893093
TI  - Ligation of CD40 in Human Muller Cells Induces P2X7 Receptor-Dependent Death of
      Retinal Endothelial Cells.
AB  - Purpose: Cluster of differentiation 40 (CD40) is required for retinal capillary
      degeneration in diabetic mice, a process mediated by the retinal endothelial
      cells (REC) death. However, CD40 activates prosurvival signals in endothelial
      cells. The purpose of this study was to identify a mechanism by which CD40
      triggers programmed cell death (PCD) of RECs and address this paradox. Methods:
      Human RECs and Muller cells were incubated with CD154 and L-N6-(1
      Iminoethyl)lysine (L-Nil, nitric oxide synthase 2 inhibitor), alpha-lipoic acid
      (inhibitor of oxidative stress), anti-Fas ligand antibody, or A-438079 (P2X7
      adenosine triphosphate [ATP] receptor inhibitor). Programmed cell death was
      analyzed by fluorescence-activated cell sorting (FACS) or Hoechst/propidium
      iodide staining. Release of ATP was measured using a luciferase-based assay. Mice
      were made diabetic with streptozotocin. Expression of P2X7 was assessed by FACS,
      quantitative PCR, or immunohistochemistry. Results: Ligation of CD40 in primary
      RECs did not induce PCD. In contrast, in the presence of primary CD40+ Muller
      cells, CD40 stimulation caused PCD of RECs that was not impaired by L-Nil, alpha
      lipoic acid, or anti-Fas ligand antibody. We found CD40 did not trigger TNF-alpha
      or IL-1beta secretion. Primary Muller cells released extracellular ATP in
      response to CD40 ligation. Inhibition of P2X7 (A-438079) impaired PCD of RECs;
      CD40 upregulated P2X7 in RECs, making them susceptible to ATP/P2X7-mediated PCD.
      Diabetic mice upregulated P2X7 in the retina and RECs in a CD40-dependent manner.
      Conclusions: Cluster of differentiation 40 induces PCD of RECs through a dual
      mechanism: ATP release by Muller cells and P2X7 upregulation in RECs. These
      findings are likely of in vivo relevance since CD40 upregulates P2X7 in RECs in
      diabetic mice and CD40 is known to be required for retinal capillary
      degeneration.

PMID- 27893094
TI  - Comparison of Patient-Specific Computational Modeling Predictions and Clinical
      Outcomes of LASIK for Myopia.
AB  - Purpose: To assess the predictive accuracy of simulation-based LASIK outcomes.
      Methods: Preoperative and 3-month post-LASIK tomographic data from 20 eyes of 12
      patients who underwent wavefront-optimized LASIK for myopia were obtained
      retrospectively. Patient-specific finite element models were created and case
      specific treatment settings were simulated. Simulated keratometry (SimK) values
      and the mean tangential curvature of the central 3 mm (Kmean) were obtained from
      the anterior surfaces of the clinical tomographies, and computational models were
      compared. Correlations between Kmean prediction error and patient age,
      preoperative corneal hysteresis (CH), and corneal resistance factor (CRF) were
      assessed. Results: The mean difference for Kmean between simulated and actual
      post-LASIK cases was not statistically significant (-0.13 +/- 0.36 diopters [D],
      P = 0.1). The mean difference between the surgically induced clinical change in
      Kmean and the model-predicted change was -0.11 +/- 0.34 D (P = 0.2). Kmean
      prediction error was correlated to CH, CRF, and patient age (r = 0.63, 0.53, and
      0.5, respectively, P < 0.02), and incorporation of CH values into predictions as
      a linear offset increased their accuracy. Simulated changes in Kmean accounted
      for 97% of the variance in actual spherical equivalent refractive change.
      Conclusions: Clinically feasible computational simulations predicted corneal
      curvature and manifest refraction outcomes with a level of accuracy in myopic
      LASIK cases that approached the limits of measurement error. Readily available
      preoperative biomechanical measures enhanced simulation accuracy. Patient
      specific simulation may be a useful tool for clinical guidance in de novo LASIK
      cases.

PMID- 27893095
TI  - Functional Reading Independence (FRI) Index: A New Patient-Reported Outcome
      Measure for Patients With Geographic Atrophy.
AB  - Purpose: To develop and validate the Functional Reading Independence (FRI) Index,
      a new patient-reported outcome measure assessing reading activities in
      individuals with geographic atrophy (GA) due to age-related macular degeneration.
      Methods: The Index was developed through expert consultation and qualitative
      patient interviews. Reliability, validity, and responsiveness were tested with
      data from the Mahalo study (NCT01229215) of lampalizumab in patients with GA.
      Results: Qualitative interviews (n = 40) yielded a 10-item FRI Index, which was
      refined to seven items in quantitative testing (n = 100). Strong internal
      consistency (marginal reliability = 0.90) and reproducibility (intraclass
      correlation coefficient = 0.86) were shown. Known-group validity testing for
      baseline mean FRI Index scores showed differences (mean [SD]) between patients
      with Minnesota Low-Vision Reading test reading speed >=80 vs. <80 words per
      minute (3.0 [0.7] vs. 1.9 [0.7]; P < 0.001), and between patients above vs. below
      median values on the National Eye Institute Visual Function Questionnaire-25 (NEI
      VFQ-25) score (2.9 [0.7] vs. 2.1 [0.8]; P < 0.001). Convergent validity with
      binocular measures was strong (Spearman's correlation = 0.72 for reading speed,
      0.66 for NEI-VFQ-25). Analysis of sensitivity to change revealed mean FRI Index
      score changes for patients with GA lesion size growth >=2.5 mm2/18 months of 
      0.41 (0.70) vs. -0.13 (0.61) for patients with lesion growth <2.5 mm2/18 months
      (P = 0.07). Conclusions: The FRI Index demonstrated good reliability and validity
      in patients with GA. Further study in a broader GA population is warranted to
      confirm responsiveness.

PMID- 27893096
TI  - Chemogenetic Activation of ipRGCs Drives Changes in Dark-Adapted (Scotopic)
      Electroretinogram.
AB  - Purpose: The purpose of this study was to investigate the impact of activating
      melanopsin-expressing intrinsically photosensitive retinal ganglion cells
      (ipRGCs) on dark-adapted (scotopic) electroretinograms (ERG). Methods: We used
      mice (Opn4Cre/+) expressing cre recombinase in melanopsin-expressing cells for a
      targeted gene delivery of a chemogenetic Gq-coupled receptor, hM3Dq, to ipRGCs.
      Intraperitoneal injection of clozapine N-oxide (CNO) at 5 mg/kg was used for
      acute activation of hM3Dq and thus excitation of ipRGCs in darkness. Dark-adapted
      flash ERGs were recorded across a 9-fold range of irradiances from hM3Dq
      Opn4Cre/+ and control Opn4Cre/+ mice before and after intraperitoneal injection
      of CNO. A- and b-wave amplitudes and implicit times and oscillatory potentials
      (OPs) were analyzed. Paired-flash stimuli were used to isolate cone-driven
      responses. Results: Clozapine N-oxide application suppressed a- and b-wave
      amplitudes of the dark-adapted ERG across the flash intensity range in hM3Dq
      Opn4Cre/+ mice compared to control mice. Examination of the normalized irradiance
      response functions revealed a shift in b-wave but not a-wave sensitivity. No
      changes in a- and b-wave implicit times were detected. Total OP amplitudes were
      also reduced in hM3Dq Opn4Cre/+ mice compared to controls following CNO
      administration. The paired-flash method revealed reduction in both the first
      (rods and cones) and second (cones only) flash response. Conclusions: Acute and
      selective activation of ipRGCs modulates the amplitude of both a- and b-waves of
      the scotopic ERG, indicating that the influence of this ganglion cell class on
      the retinal physiology extends to the photoreceptors as well as their downstream
      pathways.

PMID- 27893098
TI  - Vitreal Cytokine Profile Differences Between Eyes With Epiretinal Membranes or
      Macular Holes.
AB  - Purpose: Cytokines play an important role in cell signaling in inflammatory and
      repair processes, also within the posterior segment of the eye. These molecules
      are thus implicated in the pathophysiology of several vitreoretinal diseases. In
      the present study, we compared vitreal cytokine profiles in patients with
      idiopathic epiretinal membranes (ERMs) and idiopathic full-thickness macular
      holes (MHs) without epiretinal membranes. Methods: Native vitreal humor was
      collected during elective pars plana vitrectomy for the treatment of macular
      pathologies (group 1: ERM; group 2: MH) from patients without any other ocular or
      systemic disease. The concentrations of 43 chemokines and cytokines were measured
      in parallel by multiplex beads analysis. Intergroup comparisons were conducted
      using the Mann-Whitney U test and Bonferroni's correction, at a level of
      significance of P < 0.0012. Results: Vitreal samples from 31 patients with ERMs
      (group 1) and from 30 with MHs (group 2) were analyzed. For 12 of the tested
      cytokines (GM-CSF, MCP-1, MIF, CCL15, CCL20, CCL17, CX3CL1, CXCL10, CXCL16, and
      TGF-beta-1, -2, and -3), no intergroup differences were revealed; for the other
      31, the concentrations were higher in the ERM than in the MH group (P < 0.0012 in
      each case). Conclusions: The vitreal levels of 72% of the tested cytokines were
      higher in ERM than in MH. This indicates that even in the absence of clinical
      markers, activation of inflammatory and profibrotic mechanisms is implicated in
      the progression of ERMs. Although frequently used as such in the past, eyes with
      ERMs should be considered with caution as a healthy control group.

PMID- 27893097
TI  - Benefit of Measuring Anterior Segment Structures Using an Increased Number of
      Optical Coherence Tomography Images: The Chinese American Eye Study.
AB  - Purpose: The purpose of this study was to evaluate the benefit of analyzing an
      increased number of anterior segment optical coherence tomography (AS-OCT) images
      on measurement values of various anterior segment parameters. Methods: Subjects
      for this cross-sectional study were recruited from the Chinese American Eye Study
      (CHES), a population-based study in Los Angeles, CA. Thirty-two AS-OCT images
      were acquired from one eye each of 83 consecutive subjects. Sixteen parameters
      were analyzed in each image, including angle opening distance (AOD), angle recess
      area (ARA), trabecular iris space area (TISA), trabecular iris angle (TIA),
      scleral spur angle (SSAngle), lens vault (LV), pupillary diameter (PD), anterior
      chamber depth (ACD), anterior chamber width (ACW), iris area (IA), and anterior
      chamber area (ACA). Data from 1, 2, 4, 8, 16, or 32 OCT images were averaged
      across subjects to calculate the range and mean of measurement values for each
      parameter. Results: Anatomical variations were poorly captured with fewer OCT
      images for AOD, ARA, TISA, SSAngle, IA, and LV. For these parameters, the range
      and mean of measurement values obtained from one OCT image deviated from 32-image
      values by up to 43.9% and 13.3% of the 32-image mean, respectively. These
      deviations decreased when additional OCT images were analyzed. Deviations from 32
      image range and mean values were less pronounced regardless of image number for
      PD, ACD, ACW, and ACA, measuring up to 3.5% and 5.0%, respectively. Conclusions:
      A multi-image approach should be the standard in OCT-based studies of AOD, ARA,
      TISA, TIA, SSAngle, IA, and LV.

PMID- 27893099
TI  - Electrically Evoked Responses in the Rabbit Cortex Induced by Current Steering
      With Penetrating Optic Nerve Electrodes.
AB  - Purpose: Current steering is a neural stimulation strategy that uses simultaneous
      stimulation of adjacent electrodes to produce additional intermediate stimulation
      sites and thus improves spatial resolution. We investigated the feasibility of
      current steering using electrophysiological and computational methods after
      implanting paired penetrating electrodes into the rabbit's optic nerve (ON).
      Methods: Penetrating electrodes at different interelectrode distances were
      implanted into the ON and electrically evoked cortical potentials (EEPs) in V1
      recorded with a 6 * 8 array. The current thresholds, EEP amplitudes, and spatial
      distributions were analyzed during current steering. Computational simulation
      studies were performed based on finite element models to calculate the area and
      spatial distribution of recruited ON fibers using a current steering stimulation
      strategy. Results: Threshold reduction and EEP amplitude enhancement were found
      with simultaneous stimulation of closely spaced electrode pairs. Spatially
      shifted cortical responses were achieved using current steering, whereas the
      amplitudes and spatial spreads of the responses were similar to that elicited by
      a single electrode. Computational simulations suggested that the centroid of the
      ON recruitment area could be modulated by current steering while the total
      recruitment area did not show any appreciable variability at a fixed current
      intensity. Conclusions: Current steering is a useful strategy to enhance the
      spatial resolution of an ON prosthesis without increasing the number of physical
      electrodes. This study provides useful information for optimizing the design of
      stimulation strategies with a penetrating ON prosthesis.

PMID- 27893101
TI  - Comparison of Local Structure-Function Relationships and Dynamic Range in
      Glaucoma.

PMID- 27893100
TI  - Do Intense Perimetric Stimuli Saturate the Healthy Visual System?
AB  - Purpose: A recent proposal for why glaucomatous perimetric sensitivities of
      approximately 15 to 19 dB or less are unreliable involves the idea that the
      neural response of normal retinal ganglion cells saturates for intense perimetric
      stimuli. A predicted consequence of this saturation is that the neural response
      for two different high intensity stimuli will be the same, leading to an
      inability to discriminate between them. We test that prediction. Methods: We used
      a two-interval forced-choice method of constant stimuli (7 steps, 40
      presentations/step) to measure the ability of four healthy observers to
      discriminate between different intensity Size III perimetric stimuli at 0 degrees
      , 9 degrees , and 21 degrees  eccentricity. The lower intensity stimulus for each
      discrimination was either 27, 23, 19, 15, or 11 dB (Humphrey Field Analyzer
      equivalents). Results: Foveally, discrimination performance exceeded 90% for all
      observers provided the more intense stimulus was made sufficiently intense, even
      if the lower intensity stimulus in the pair was itself already intense (<=19 dB).
      The shapes of the curves were similar across all lower intensity stimulus values
      investigated. At 21 degrees , discrimination performance exceeded 90% in three of
      the four observers despite the lower intensity stimulus being 19 dB. Conclusions:
      Observers can reliably discriminate between two different, but both very intense,
      perimetric stimuli, indicating that responses of the human visual system are not
      saturated by such stimuli. Therefore, the cause of high perimetric test-retest
      variability is not readily predicted from our current knowledge of how normal
      ganglion cells respond to high intensity stimuli.

PMID- 27893102
TI  - Author Response: Comparison of Local Structure-Function Relationships and Dynamic
      Range in Glaucoma.

PMID- 27893104
TI  - Stronger Association of CDKN2B-AS1 Variants in Female Normal-Tension Glaucoma
      Patients in a Japanese Population.

PMID- 27893103
TI  - Potential of Small Molecule-Mediated Reprogramming of Rod Photoreceptors to Treat
      Retinitis Pigmentosa.
AB  - Purpose: Mutations in rod photoreceptor genes can cause retinitis pigmentosa
      (RP). Rod gene expression is regulated by the nuclear hormone receptor, Nr2e3.
      Genetic deletion of Nr2e3 reprograms rods into cells that resemble cone
      photoreceptors, and might therefore prevent their death from some forms of RP.
      There are no identified ligands for Nr2e3; however, reverse agonists might mimic
      the genetic rescue effect and may be therapeutically useful for the treatment of
      RP. Methods: We screened for small molecule modulators of Nr2e3 using primary
      retinal cell cultures and characterized the most potent, which we have named
      photoregulin1 (PR1), in vitro and in vivo. We also tested the ability of PR1 to
      slow the progression of photoreceptor degeneration in two common mouse models of
      autosomal dominant RP, the RhoP23H and the Pde6brd1 mutations. Results: In
      developing retina, PR1 causes a decrease in rod gene expression and an increase
      in S opsin+ cones. Photoregulin1 continues to inhibit rod gene expression in
      adult mice. When applied to two mouse models of RP, PR1 slows the degeneration of
      photoreceptors. Conclusions: Chemical compounds identified as modulators of Nr2e3
      activity may be useful for the treatment of RP through their effects on
      expression of disease-causing mutant genes.

PMID- 27893105
TI  - Author Response: Stronger Association of CDKN2B-AS1 Variants in Female Normal
      Tension Glaucoma Patients in a Japanese Population.

PMID- 27893107
TI  - Diurnal Fluctuation of Intraocular Pressure.

PMID- 27893108
TI  - Choroidal Thickness Influences Near-Infrared Reflectance Intensity in Eyes With
      Geographic Atrophy Due To Age-Related Macular Degeneration.
AB  - Purpose: To evaluate the effects of retinal and choroidal thickness on near
      infrared reflectance (NIR) scanning laser ophthalmoscopy in eyes with geographic
      atrophy (GA) secondary to non-neovascular age-related macular degeneration (AMD).
      Methods: This was a cross-sectional review of the clinical records and multimodal
      imaging data of eyes diagnosed with GA secondary to non-neovascular AMD. Imaging
      modalities included color fundus photography, fundus autofluorescence, NIR, and
      structural spectral-domain optical coherence tomography (SD-OCT). On SD-OCT
      images, the foveal retina thickness and the subfoveal choroidal thickness were
      measured by two independent readers. Near-infrared reflectance intensity within
      areas of GA was subjectively graded as hyperreflective, isoreflective, or
      hyporeflective and objectively estimated by using ImageJ to calculate the mean
      gray scale value within each GA area. A linear regression analysis was performed
      to model the relationship between mean NIR gray scale value and retinal and
      choroidal thickness. Results: One hundred four eyes of 104 patients with a mean
      age of 81.3 years (SD: +/-8.3) were included. The area of GA was hyperreflective
      on NIR in 88 eyes (85%), isoreflective in 13 eyes (12%), and hyporeflective in 3
      eyes (3%). The mean foveal retinal thickness was 101.5 MUm (SD: +/-54) showing no
      significant relationship with mean NIR (P = 0.464); and the mean subfoveal
      choroidal thickness was 172.6 MUm (SD: +/-114.7) showing a statistically
      significant relationship with mean NIR intensity in the linear regression
      analysis (r = 0.590; r2 = 0.348; P < 0.00001). Conclusions: Variations in
      choroidal thickness appear to influence NIR intensity in areas of GA and have the
      potential to affect image interpretation. The recognition of this relationship
      may provide useful information regarding choroidal thickness.

PMID- 27893106
TI  - Evidence for a GPR18 Role in Diurnal Regulation of Intraocular Pressure.
AB  - Purpose: The diurnal cycling of intraocular pressure (IOP) was first described in
      humans more than a century ago. This cycling is preserved in other species. The
      physiologic underpinning of this diurnal variation in IOP remains a mystery, even
      though elevated pressure is indicated in most forms of glaucoma, a common cause
      of blindness. Once identified, the system that underlies diurnal variation would
      represent a natural target for therapeutic intervention. Methods: Using
      normotensive mice, we measured the regulation of ocular lipid species by the
      enzymes fatty acid amide hydrolase (FAAH) and N-arachidonoyl
      phosphatidylethanolamine phospholipase (NAPE-PLD), mRNA expression of these
      enzymes, and their functional role in diurnal regulation of IOP. Results: We now
      report that NAPE-PLD and FAAH mice do not exhibit a diurnal cycling of IOP. These
      enzymes produce and break down acylethanolamines, including the endogenous
      cannabinoid anandamide. The diurnal lipid profile in mice shows that levels of
      most N-acyl ethanolamines and, intriguingly, N-arachidonoyl glycine (NAGly),
      decline at night: NAGly is a metabolite of arachidonoyl ethanolamine and a potent
      agonist at GPR18 that lowers intraocular pressure. The GPR18 blocker O1918 raises
      IOP during the day when pressure is low, but not at night. Quantitative PCR
      analysis shows that FAAH mRNA levels rise with pressure, suggesting that FAAH
      mediates the changes in pressure. Conclusions: Our results support FAAH-dependent
      NAGly action at GPR18 as the physiologic basis of the diurnal variation of
      intraocular pressure in mice.

PMID- 27893109
TI  - Safety and Efficacy Clinical Trials for SYL1001, a Novel Short Interfering RNA
      for the Treatment of Dry Eye Disease.
AB  - Purpose: To evaluate the efficacy and safety of SYL1001, a short interfering (si)
      RNA targeting the transient receptor potential cation channel subfamily V member
      1 (TRPV1), for the treatment of dry eye disease (DED). Methods: This study
      combines a phase I and two phase II clinical trials to test different doses of
      SYL1001 in a total of 156 healthy subjects and patients with DED. After 10 days
      of treatment, the primary efficacy endpoints were the effect on (1) the scoring
      in the Visual Analogue Scale (VAS) and Ocular Surface Disease Index (OSDI)
      questionnaires, and (2) ocular tolerance evaluated by corneal fluorescein
      staining and conjunctival hyperemia. Secondary endpoints included the assessment
      of systemic and local tolerance. Results: Topical administration of SYL1001
      1.125% once daily produced a significant decrease in VAS scores compared with
      placebo from day 4 until the end of treatment (change from baseline at day 10: 
      1.73 +/- 0.32 vs. -0.91 +/- 0.34; P = 0.013). For all treatments, OSDI scores
      were significantly reduced compared to their respective baseline values (P <
      0.01), although no significant changes were detected between groups. Conjunctival
      hyperemia (quantified as normal or abnormal) significantly improved after
      instillation of SYL1001 1.125% compared with placebo (50% vs. 20%; P < 0.05).
      Excellent tolerability was reported, with no differences in the rates of
      occurrence of adverse events between groups. Conclusion: These trials achieved
      their primary endpoints of identifying the most effective dose of SYL1001
      (1.125%). SYL1001 showed a large safety margin and may provide novel therapeutic
      opportunity for the relief of dry eye. (ClinicalTrials.gov numbers, NCT01438281,
      NCT01776658, and NCT02455999.).

PMID- 27893110
TI  - The Art of Plastic Surgery.

PMID- 27893111
TI  - Mixing Study for Evaluation of Abnormal Coagulation Testing.

PMID- 27893112
TI  - Reducing Adverse Drug Events: The Need to Rethink Outpatient Prescribing.

PMID- 27893113
TI  - The Promise of Palliative Care: Translating Clinical Trials to Clinical Care.

PMID- 27893114
TI  - NIH Launches Study of Children's Environmental Exposures.

PMID- 27893115
TI  - Under Affordable Care Act, Uninsured Rates Fell Across Demographic Groups.

PMID- 27893116
TI  - New Report Outlines Roadmap for Preventing Youth Suicide.

PMID- 27893118
TI  - Problems Confronting Medical Investigators.

PMID- 27893119
TI  - Infectious Disease Mortality Trends in the United States, 1980-2014.

PMID- 27893120
TI  - Revisions to the Nutrition Facts Label.

PMID- 27893121
TI  - Euthanasia or Assisted Suicide in Patients With Psychiatric Illness.

PMID- 27893122
TI  - Cost-effectiveness of PCSK9 Inhibitor Therapy.

PMID- 27893123
TI  - Revisions to the Nutrition Facts Label-Reply.

PMID- 27893124
TI  - Euthanasia or Assisted Suicide in Patients With Psychiatric Illness-Reply.

PMID- 27893125
TI  - Cost-effectiveness of PCSK9 Inhibitor Therapy-Reply.

PMID- 27893126
TI  - Combined Incentives and Restrictions Lead to Better Food Choices.

PMID- 27893127
TI  - Low Prostate-Cancer Mortality No Matter the Treatment.

PMID- 27893128
TI  - Human Milk Protein Prevents Infections in Preterm Infants.

PMID- 27893129
TI  - US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.
AB  - Importance: The Patient Protection and Affordable Care Act of 2010 brought
      attention to adverse drug events in national patient safety efforts. Updated,
      detailed, nationally representative data describing adverse drug events can help
      focus these efforts. Objective: To describe the characteristics of emergency
      department (ED) visits for adverse drug events in the United States in 2013-2014
      and describe changes in ED visits for adverse drug events since 2005-2006.
      Design, Setting, and Participants: Active, nationally representative, public
      health surveillance in 58 EDs located in the United States and participating in
      the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event
      Surveillance project. Exposures: Drugs implicated in ED visits. Main Outcomes and
      Measures: National weighted estimates of ED visits and subsequent
      hospitalizations for adverse drug events. Results: Based on data from 42 585
      cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events
      occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%
      32.4%) of ED visits for adverse drug events resulted in hospitalization. An
      estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events
      occurred among adults aged 65 years or older in 2013-2014 compared with an
      estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the
      highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants,
      antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI,
      44.2%-49.7%) of ED visits for adverse drug events, which included clinically
      significant adverse events, such as hemorrhage (anticoagulants), moderate to
      severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe
      neurological effects (diabetes agents). Since 2005-2006, the proportions of ED
      visits for adverse drug events from anticoagulants and diabetes agents have
      increased, whereas the proportion from antibiotics has decreased. Among children
      aged 5 years or younger, antibiotics were the most common drug class implicated
      (56.4%; 95% CI, 51.8%-61.0%). Among children and adolescents aged 6 to 19 years,
      antibiotics also were the most common drug class implicated (31.8%; 95% CI, 28.7%
      34.9%) in ED visits for adverse drug events, followed by antipsychotics (4.5%;
      95% CI, 3.3%-5.6%). Among older adults (aged >=65 years), 3 drug classes
      (anticoagulants, diabetes agents, and opioid analgesics) were implicated in an
      estimated 59.9% (95% CI, 56.8%-62.9%) of ED visits for adverse drug events; 4
      anticoagulants (warfarin, rivaroxaban, dabigatran, and enoxaparin) and 5 diabetes
      agents (insulin and 4 oral agents) were among the 15 most common drugs
      implicated. Medications to always avoid in older adults according to Beers
      criteria were implicated in 1.8% (95% CI, 1.5%-2.1%) of ED visits for adverse
      drug events. Conclusions and Relevance: The prevalence of emergency department
      visits for adverse drug events in the United States was estimated to be 4 per
      1000 individuals in 2013 and 2014. The most common drug classes implicated were
      anticoagulants, antibiotics, diabetes agents, and opioid analgesics.

PMID- 27893130
TI  - Effect of Inpatient Palliative Care on Quality of Life 2 Weeks After
      Hematopoietic Stem Cell Transplantation: A Randomized Clinical Trial.
AB  - Importance: During hospitalization for hematopoietic stem cell transplantation
      (HCT), patients receive high-dose chemotherapy before transplantation and
      experience significant physical and psychological symptoms and poor quality of
      life (QOL). Objective: To assess the effect of inpatient palliative care on
      patient- and caregiver-reported outcomes during hospitalization for HCT and 3
      months after transplantation. Design, Setting, and Participants: Nonblinded
      randomized clinical trial among 160 adults with hematologic malignancies
      undergoing autologous/allogeneic HCT and their caregivers (n = 94). The study was
      conducted from August 2014 to January 2016 in a Boston hospital; follow-up was
      completed in May 2016. Interventions: Patients assigned to the intervention
      (n=81) were seen by palliative care clinicians at least twice a week during HCT
      hospitalization; the palliative intervention was focused on management of
      physical and psychological symptoms. Patients assigned to standard transplant
      care (n=79) could be seen by palliative care clinicians on request. Main Outcomes
      and Measures: Primary: change in patient QOL from baseline to week 2; secondary:
      patient-assessed mood, fatigue, and symptom burden scores at baseline, 2 weeks,
      and 3 months after HCT and caregiver-assessed QOL and mood at baseline and 2
      weeks after HCT. Results: Among 160 enrolled patients (mean age, 60 [SD, 13.3]
      years; 91 women [56.9%]; median hospital stay, 21 days) and 94 caregivers, 157
      (98.1%) and 89 (94.7%), respectively, completed 2-week follow-up, and 149
      patients (93.1%) completed 3-month follow-up. Patients in the intervention group
      reported a smaller decrease in QOL from baseline to week 2 (mean baseline score,
      110.26; week 2 score, 95.46; mean change, -14.72) compared with patients in the
      control group (mean baseline score, 106.83; week 2 score, 85.42; mean change, 
      21.54; difference between groups, -6.82; 95% CI, -13.48 to -0.16; P = .045).
      Among the secondary outcomes, from baseline to week 2, patients in the
      intervention group vs those in the control group had less increase in depression
      (mean, 2.43 vs 3.94; mean difference, 1.52; 95% CI, 0.23-2.81; P = .02), lower
      anxiety (mean, -0.80 vs 1.12; mean difference, 1.92; 95% CI, 0.83-3.01; P <
      .001), no difference in fatigue (mean, -10.30 vs -13.65; mean difference, -3.34;
      95% CI, -7.25 to 0.56; P = .09), and less increase in symptom burden (mean, 17.35
      vs 23.14; mean difference, 5.80; 95% CI, 0.49-11.10; P = .03). At 3 months after
      HCT, intervention patients vs control patients had higher QOL scores (mean,
      112.00 vs 106.66; mean difference, 5.34; 95% CI, 0.04-10.65; P = .048) and less
      depression symptoms (mean, 3.49 vs 5.19; mean difference, -1.70; 95% CI, -2.75 to
      -0.65; P = .002) but no significant differences in anxiety, fatigue, or symptom
      burden. From baseline to week 2 after HCT, caregivers of patients in the
      intervention group vs caregivers of patients in the control group reported no
      significant differences in QOL or anxiety but had a smaller increase in
      depression (mean, 0.25 vs 1.80; mean difference, 1.55; 95% CI, 0.14-2.96; P =
      .03). Conclusions and Relevance: Among adults at a single institution undergoing
      HCT for hematologic malignancy, the use of inpatient palliative care compared
      with standard transplant care resulted in a smaller decrease in QOL 2 weeks after
      transplantation. Further research is needed for replication and to assess longer
      term outcomes and cost implications. Trial Registration: clinicaltrials.gov
      Identifier: NCT02207322.

PMID- 27893132
TI  - Essential Tremor.

PMID- 27893134
TI  - The Good-Enough Parent.

PMID- 27893131
TI  - Association Between Palliative Care and Patient and Caregiver Outcomes: A
      Systematic Review and Meta-analysis.
AB  - Importance: The use of palliative care programs and the number of trials
      assessing their effectiveness have increased. Objective: To determine the
      association of palliative care with quality of life (QOL), symptom burden,
      survival, and other outcomes for people with life-limiting illness and for their
      caregivers. Data Sources: MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL to July
      2016. Study Selection: Randomized clinical trials of palliative care
      interventions in adults with life-limiting illness. Data Extraction and
      Synthesis: Two reviewers independently extracted data. Narrative synthesis was
      conducted for all trials. Quality of life, symptom burden, and survival were
      analyzed using random-effects meta-analysis, with estimates of QOL translated to
      units of the Functional Assessment of Chronic Illness Therapy-palliative care
      scale (FACIT-Pal) instrument (range, 0-184 [worst-best]; minimal clinically
      important difference [MCID], 9 points); and symptom burden translated to the
      Edmonton Symptom Assessment Scale (ESAS) (range, 0-90 [best-worst]; MCID, 5.7
      points). Main Outcomes and Measures: Quality of life, symptom burden, survival,
      mood, advance care planning, site of death, health care satisfaction, resource
      utilization, and health care expenditures. Results: Forty-three RCTs provided
      data on 12 731 patients (mean age, 67 years) and 2479 caregivers. Thirty-five
      trials used usual care as the control, and 14 took place in the ambulatory
      setting. In the meta-analysis, palliative care was associated with statistically
      and clinically significant improvements in patient QOL at the 1- to 3-month
      follow-up (standardized mean difference, 0.46; 95% CI, 0.08 to 0.83; FACIT-Pal
      mean difference, 11.36] and symptom burden at the 1- to 3-month follow-up
      (standardized mean difference, -0.66; 95% CI, -1.25 to -0.07; ESAS mean
      difference, -10.30). When analyses were limited to trials at low risk of bias (n
      = 5), the association between palliative care and QOL was attenuated but remained
      statistically significant (standardized mean difference, 0.20; 95% CI, 0.06 to
      0.34; FACIT-Pal mean difference, 4.94), whereas the association with symptom
      burden was not statistically significant (standardized mean difference, -0.21;
      95% CI, -0.42 to 0.00; ESAS mean difference, -3.28). There was no association
      between palliative care and survival (hazard ratio, 0.90; 95% CI, 0.69 to 1.17).
      Palliative care was associated consistently with improvements in advance care
      planning, patient and caregiver satisfaction, and lower health care utilization.
      Evidence of associations with other outcomes was mixed. Conclusions and
      Relevance: In this meta-analysis, palliative care interventions were associated
      with improvements in patient QOL and symptom burden. Findings for caregiver
      outcomes were inconsistent. However, many associations were no longer significant
      when limited to trials at low risk of bias, and there was no significant
      association between palliative care and survival.

PMID- 27893135
TI  - Screening for Colorectal Cancer and Evolving Issues for Physicians and Patients:
      A Review.
AB  - Importance: Colorectal cancer (CRC) is the second-leading cause of cancer death
      in the United States. Screening can reduce CRC mortality and incidence, and
      numerous screening options, although available, complicate informed decision
      making. This review provides evidence-based tools for primary care physicians to
      identify patients with higher-than-average-risk and engage patients in informed
      decision making about CRC screening options. Observations: Recently, the US
      Preventive Services Task Force recommended any of 8 CRC screening approaches for
      average-risk individuals, beginning at age 50 years. Only 2 methods have been
      shown in randomized clinical trials to reduce mortality: fecal occult blood
      testing and flexible sigmoidoscopy. Of the 8 programs, screenings using the fecal
      immunochemical test annually and colonoscopy every 10 years are now the most
      commonly used tests in the United States and among the most effective in reducing
      CRC mortality as determined by decision models. With the exception of primary
      screening using colonoscopy, all of the other screening approaches have multiple
      steps. Adherence to each phase of a multistep program is critical to achieving
      maximal effectiveness of the screening program. It is likely that each of the
      recommended programs can reduce CRC mortality, but other key outcomes may differ
      such as lifetime burden of colonoscopy, complications, patient acceptance, and
      cost. Decisions about the timing of screening cessation should be individualized.
      Conclusions and Relevance: CRC screening is effective if patients adhere to the
      steps in each screening program. There is no evidence that one program is
      superior to another. Informed decision-making tools are provided to assist
      patients and clinicians with the goal of improving adherence to effective
      screening.

PMID- 27893137
TI  - Trade, Investment, and Tobacco: Philip Morris v Uruguay.

PMID- 27893138
TI  - Achieving the Triple Aim Through Disruptive Innovations in Self-care.

PMID- 27893139
TI  - Fewer Opioids, More Exercise for Severe Joint Pain From Arthritis.

PMID- 27893140
TI  - Undervaccinated Kindergarteners.

PMID- 27893141
TI  - Ten Tips for Maximizing the Effectiveness of Emergency Medicine Procedure
      Laboratories.

PMID- 27893142
TI  - Assessment of Hospital Staff's Knowledge of Osteopathic Manipulative Medicine: A
      Survey-Based Study.
AB  - CONTEXT: Research has shown that osteopathic manipulative treatment (OMT) in
      hospitalized patients can shorten hospital length of stay. However, hospital
      staff may be unfamiliar with OMT and its use in this setting. OBJECTIVE: To
      assess a hospital staff's knowledge of osteopathic manipulative medicine (OMM)
      and investigate whether there is a correlation between job category and knowledge
      of OMM. METHODS: The study used a 13-item survey that was developed using
      SurveyMonkey. A brief description stating the purpose of the survey with a
      hyperlink to the survey was sent in an e-mail to the employee LISTSERV at Good
      Samaritan Regional Medical Center. This LISTSERV included all 1933 employees at
      the medical center. After 10 days the survey was closed and the responses were
      collected and interpreted by a statistician and the primary investigator.
      Incomplete surveys were included. RESULTS: A total of 474 employees (24.5%)
      returned the survey. Of these respondents, 267 (66.9%) responded that OMM could
      be done in the hospital. Only 97 respondents (24.6%) reported seeing OMM
      performed in the hospital. Physicians had the highest awareness of OMM (53.7%),
      compared with all other employees (7%). CONCLUSION: An overall lack of knowledge
      exists regarding OMM among hospital staff, especially nonphysician employees, at
      a medical clinic.

PMID- 27893143
TI  - Association Between WIC Enrollment and Exclusive Breastfeeding at 3 Months
      Postpartum Among Low-Income Mothers.
AB  - CONTEXT: Existing literature suggests participation in the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC) in the prenatal and
      postnatal periods is associated with lower rates of breastfeeding among WIC
      eligible mothers. However, minimal research has been published on the association
      between WIC enrollment and exclusive breastfeeding. OBJECTIVE: To examine the
      association between WIC exposure and exclusive breastfeeding at 3 months
      postpartum. METHODS: We conducted a secondary data analysis using information on
      784 low-income women who participated in the longitudinal population-based Infant
      Feeding Practices Study II between May 2005 and June 2007. The main outcome of
      interest was exclusive breastfeeding at 3 months postpartum. Logistic regression
      analysis was used to estimate OR and 95% CI for exclusive breastfeeding relative
      to WIC enrollment status, controlling for the confounding effects of other
      maternal characteristics. We further conducted a subgroup analysis among those
      participating in WIC prenatally to examine the association between receipt of
      information about infant feeding from WIC and exclusive breastfeeding at 3 months
      postpartum. RESULTS: The crude prevalence of exclusive breastfeeding at 3 months
      postpartum was 18.1% of women enrolled in WIC and 41.1% of WIC-eligible
      nonparticipants (P<.0001). After adjusting for sociodemographic, behavioral, and
      anthropometric factors, the odds of exclusive breastfeeding at 3 months were
      lower for women enrolled in WIC (OR, 0.57; 95% CI, 0.37-0.88) when compared with
      women not enrolled in WIC. In the subgroup analysis, receipt of information from
      WIC about feeding infants during the prenatal period was not significantly
      associated with exclusive breastfeeding at 3 months (OR, 0.86; 95% CI, 0.39
      1.89). CONCLUSION: Women who were enrolled in WIC and who received information
      about feeding infants were less likely to exclusively breastfeed than women not
      in WIC. Continued improvement and adjustment to the existing WIC breastfeeding
      program could potentially improve these rates. Additional studies that examine
      the quality of WIC services provided, especially those pertaining to
      breastfeeding programs, are warranted.

PMID- 27893144
TI  - Effectiveness of Shared Medical Appointments Targeting the Triple Aim Among
      Patients With Overweight, Obesity, or Diabetes.
AB  - BACKGROUND: Obesity and diabetes are epidemic in the United States, with many
      treatment options having limited long-term efficacy. A possible effective medical
      management tool is the shared medical appointment (SMA), which offers an
      efficient and cost-effective approach to behavior change and aligns with the
      Triple Aim (reduce costs, improve population health, and improve patient care
      experience) set forth by the Institute for Healthcare Improvement. OBJECTIVES: To
      assess the effectiveness of SMAs to achieve the Triple Aim and to improve the
      management of overweight/obesity or diabetes. METHODS: Peer-reviewed literature
      from PubMed was searched by the keywords shared medical appointments, group
      medical appointment, and group medical visit, with no date restrictions and
      limited to English publications with sample sizes greater than or equal to 20.
      RESULTS: Eight articles met inclusion criteria. The Triple Aim was not referenced
      in the studies, but most reported some combination of reduced costs, improved
      care, and improved outcomes or patient satisfaction. CONCLUSIONS: Potential
      benefits of SMAs include improved patient outcomes and satisfaction. Osteopathic
      and, in particular, primary care medicine could likely benefit from moving toward
      greater adoption of SMAs; however, more randomized controlled trials are needed
      to assess their effectiveness with regard to the Triple Aim.

PMID- 27893145
TI  - Are Low-Carbohydrate Diets Safe and Effective?

PMID- 27893146
TI  - Alternative Scheduling Models: Improving Continuity of Care, Medical Outcomes,
      and Graduate Medical Education in Resident Ambulatory Training.
AB  - An association has been consistently made about continuity of care with improved
      quality of care and improved medical outcomes. However, resident ambulatory block
      scheduling prevents the optimization of continuity of care in ambulatory clinical
      education. The author performed a PubMed search for studies examining continuity
      of care and curriculum scheduling in US primary care residency clinics. These
      studies indicate the success of an X + Y scheduling model in resident ambulatory
      training. Additional benefits have also been noted, including improved clinical
      teaching and learning, increased sense of teamwork, increased resident
      satisfaction, improved recruitment and retention, improved patient satisfaction,
      and elimination of year-end patient care issues after graduation. Many allopathic
      institutions have begun to implement such curricular changes with demonstrated
      success. The author argues that osteopathic graduate medical education should
      embrace the X + Y scheduling model.

PMID- 27893147
TI  - Update on the Pharmacology and Legal Status of Kratom.
AB  - Kratom (Mitragyna speciosa) is a plant indigenous to Southeast Asia. Its leaves
      and the teas brewed from them have long been used by people in that region to
      stave off fatigue and to manage pain and opioid withdrawal. In a comprehensive
      review published in 2012, Prozialeck et al presented evidence that kratom had
      been increasingly used for the self-management of opioid withdrawal and pain in
      the United States. At the time, kratom was classified as a legal herbal product
      by the US Drug Enforcement Administration. Recent studies have confirmed that
      kratom and its chemical constituents do have useful pharmacologic actions.
      However, there have also been increasing numbers of reports of adverse effects
      resulting from use of kratom products. In August 2016, the US Drug Enforcement
      Administration announced plans to classify kratom and its mitragynine
      constituents as Schedule 1 controlled substances, a move that triggered a massive
      response from kratom advocates. The purpose of this report is to highlight the
      current scientific and legal controversies regarding kratom.

PMID- 27893148
TI  - Osteopathic Manipulative Treatment for Somatic Dysfunction After Acute Severe
      Traumatic Brain Injury.
AB  - Somatic dysfunction caused by traumatic brain injury (TBI) may be managed by
      osteopathic manipulative treatment (OMT). In this case report, the authors
      describe 2 patients with severe TBI who were each treated with OMT in a level-1
      regional trauma center. Both patients received OMT beginning in the acute care
      phase of injury. Somatic dysfunction improved during the course of treatment, and
      no adverse effects of OMT were noted. More comprehensive research may clarify the
      efficacy and adverse effects of OMT as part of multimodal acute care of patients
      with severe TBI.

PMID- 27893149
TI  - Bipartite Patella.

PMID- 27893150
TI  - Client Accounts of Corrective Experiences in Psychotherapy: Implications for
      Clinical Practice.
AB  - The Patient Perceptions of Corrective Experiences in Individual Therapy (PPCEIT;
      Constantino, Angus, Friedlander, Messer, & Moertl, 2011) posttreatment interview
      guide was developed to provide clinical researchers with an effective mode of
      inquiry to identify and further explore clients' firsthand accounts of corrective
      and transformative therapy experiences and their determinants. Not only do
      findings from the analysis of client corrective experience (CE) accounts help
      identify what and how CEs happen in or as a result of psychotherapy, but the
      measure itself may also provide therapists with an effective tool to further
      enhance clients' awareness, understanding, and integration of transformative
      change experiences. Accordingly, we discuss in this afterword to the series the
      implications for clinical practice arising from (a) the thematic analysis of
      client CE accounts, drawn from a range of clinical samples and international
      research programs and (b) the clinical effect of completing the PPCEIT
      posttreatment interview inquiry. We also identify directions for future clinical
      training and research.

PMID- 27893151
TI  - Anomalies in human sex determination provide unique insights into the complex
      genetic interactions of early gonad development.
AB  - Human sex determination (SD) involves complex mutually antagonistic genetic
      interactions of testis- and ovary-determining pathways. For many years, both male
      and female SD were considered to be regulated by a linear cascade of pro-male and
      pro-female genes, respectively; however, it has become clear that male and female
      development is achieved through the repression of the alternative state. A gene
      determining the formation of a testis may function by repressing the female state
      and vice versa. Uniquely in development, SD is achieved by suppression of the
      alternate fate and maintained in adulthood by a mutually antagonistic double
      repressive pathway. Here, we review genetic data generated through large-scale
      sequencing approaches that are changing our view of how this system works,
      including the recently described recurrent NR5A1 p.R92W mutation associated with
      testis development in 46,XX children. We also review some of the unique
      challenges in the field to establish that mutations, such as this are pathogenic.
      The impending surge of new genetic data on human SD from sequencing projects will
      create opportunities for the development of mechanistic models that will clarify
      how the system operates and importantly provide data to understand how selection
      and developmental processes interact to direct the evolution of SD across
      species.

PMID- 27893152
TI  - An evaluation of high-stage cutaneous squamous cell carcinoma outcomes by sex.

PMID- 27893154
TI  - WITHDRAWN: Occlusal interventions for periodontitis in adults.
AB  - BACKGROUND: Occlusal interventions may be used in adults with periodontitis. At
      present there is little consensus regarding the indications and effectiveness of
      occlusal interventions in periodontal patients. OBJECTIVES: To identify and
      analyse the evidence for the effect of occlusal interventions on adults who have
      periodontitis in relation to tooth loss, probing depths, clinical attachment
      level, adverse effects and patient-centred outcomes. SEARCH METHODS: The search
      was last conducted in April 2008. We searched the Cochrane Oral Health Group's
      Trials Register (to 30th April 2008); the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2008, Issue 1); MEDLINE (1966 to 30th
      April 2008); and EMBASE (1980 to 30th April 2008). There were no language
      restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      assessing occlusal interventions in patients with periodontitis with a follow up
      of at least 3 months. DATA COLLECTION AND ANALYSIS: Screening of eligible
      studies, assessment of the methodological quality of the trials and data
      extraction were conducted in duplicate and independently by two review authors.
      Any disagreements between the review authors were resolved by discussion. The
      main investigator of the included trial was contacted to obtain missing
      information. The Cochrane Collaboration statistical guidelines were to be
      followed for data synthesis. MAIN RESULTS: Abstracts of 54 papers were identified
      by the search. One paper was eligible for inclusion. This paper studied the
      effect of occlusal adjustment against no occlusal adjustment in patients who were
      treated with non-surgical and surgical periodontal therapy. Methodological
      quality assessment of the included paper revealed that randomisation of the
      patients into the treatment groups was adequate. Allocation concealment, masking
      of patients and clinicians were not reported and no response to author contact
      was received.Mean change in attachment level and mean pocket depth were reported
      in the included trial. Mean difference in clinical attachment level between
      occlusal intervention and control in the non-surgical group amounted to 0.38 mm
      (95% confidence interval (CI) 0.04 to 0.72) favouring the occlusal intervention
      group and was statistically significant. In the surgical group the mean
      difference in clinical attachment level between occlusal intervention and control
      amounted to 0.40 mm (95% CI 0.05 to 0.75) favouring the occlusal intervention
      group and was also statistically significant. The difference in mean pocket depth
      reduction between the occlusal intervention and control in both the surgical and
      non-surgical groups was less than 0.1 mm and was not statistically significant.
      Tooth loss, patient-centred affects and adverse effects were not reported. Meta
      analysis was not possible due to the inclusion of only one study. AUTHORS'
      CONCLUSIONS: There is only one randomised trial that has addressed this question.
      The data from this study are inconclusive. We therefore conclude there is no
      evidence for or against the use of occlusal interventions in clinical practice.
      This question can only be addressed by adequately powered bias-protected
      randomised controlled trials.

PMID- 27893153
TI  - Efficacy and safety of dabigatran, rivaroxaban, and warfarin for stroke
      prevention in Chinese patients with atrial fibrillation: the Hong Kong Atrial
      Fibrillation Project.
AB  - BACKGROUND: Little is known about the comparative effectiveness and safety of non
      vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin in Chinese
      atrial fibrillation (AF) patients. Our aim was to compare the ischemic stroke
      risk reduction and incidence of intracranial hemorrhage (ICH) of warfarin in
      relation to quality of anticoagulation control (as reflected by time in
      therapeutic range [TTR]), and to dabigatran and rivaroxaban in a real-world
      cohort of Chinese AF patients. HYPOTHESIS: NOAC, rather than warfarin, is
      preferred in Chinese AF patients. METHODS: Of 2099 patients studied (73.1 +/-
      12.3 years, female: 44.6%, CHA2 DS2 -VASc 3.7 +/- 1.9 and HAS-BLED 2.0 +/- 1.0)
      with nonvalvular AF, 963 patients (45.9%) were on warfarin (only 16.3% had TTR
      >=65%), 669 patients were on rivaroxaban, and 467 patients were on dabigatran.
      RESULTS: After a mean follow-up of 21.7 +/- 13.4 months, there were 156 ischemic
      strokes (annual incidence of 4.10%/year), with the incidence of ischemic stroke
      being highest in patients on warfarin with TTR <65% (5.24%/year), followed by
      those on rivaroxaban (3.74%/year), and those on warfarin with TTR >=65%
      (3.35%/year), whereas patients on dabigatran had the lowest incidence of ischemic
      stroke (1.89%/year). The incidence of ICH was lowest in patients on dabigatran
      (0.39%/year) compared with those on rivaroxaban (0.52%/year) and warfarin, with
      TTR <65% (0.95%/year) and TTR >=65% (0.58%/year). Patients on rivaroxaban 20 mg
      daily had similar ischemic stroke risk (1.93%/year) and ICH risk (0.21%/year)
      compared to dabigatran. CONCLUSIONS: In Chinese AF patients, the benefits of
      warfarin therapy for stroke prevention and ICH reduction depend on TTR. Of the
      treatments compared, dabigatran, as well as rivaroxaban 20 mg daily, was
      associated with lowest ischemic stroke and ICH rates.

PMID- 27893155
TI  - Health Cards by Google: dermatologist review of the inclusivity and utility of
      the medical search application.

PMID- 27893156
TI  - Authors' response to a reply to 'A phase II randomized controlled trial of
      nicotinamide for skin cancer chemoprevention in renal transplant recipients'.

PMID- 27893157
TI  - Brown world forests: increased ungulate browsing keeps temperate trees in
      recruitment bottlenecks in resource hotspots.
AB  - Plant biomass consumers (mammalian herbivory and fire) are increasingly seen as
      major drivers of ecosystem structure and function but the prevailing paradigm in
      temperate forest ecology is still that their dynamics are mainly bottom-up
      resource-controlled. Using conceptual advances from savanna ecology, particularly
      the demographic bottleneck model, we present a novel view on temperate forest
      dynamics that integrates consumer and resource control. We used a fully factorial
      experiment, with varying levels of ungulate herbivory and resource (light)
      availability, to investigate how these factors shape recruitment of five
      temperate tree species. We ran simulations to project how inter- and
      intraspecific differences in height increment under the different experimental
      scenarios influence long-term recruitment of tree species. Strong herbivore
      driven demographic bottlenecks occurred in our temperate forest system, and
      bottlenecks were as strong under resource-rich as under resource-poor conditions.
      Increased browsing by herbivores in resource-rich patches strongly counteracted
      the increased escape strength of saplings in these patches. This finding is a
      crucial extension of the demographic bottleneck model which assumes that
      increased resource availability allows plants to more easily escape consumer
      driven bottlenecks. Our study demonstrates that a more dynamic understanding of
      consumer-resource interactions is necessary, where consumers and plants both
      respond to resource availability.

PMID- 27893158
TI  - Articular cartilage scores in cranial cruciate ligament-deficient dogs with or
      without bucket handle tears of the medial meniscus.
AB  - OBJECTIVE: To compare articular cartilage scores in cranial cruciate ligament
      (CCL)-deficient dogs with or without concurrent bucket handle tears (BHT) of the
      medial meniscus. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned
      dogs treated with arthroscopy and tibial plateau leveling osteotomy or
      extracapsular repair for complete CCL rupture (290 stifles from 264 dogs).
      METHODS: Medical records and arthroscopic images were reviewed. Medial femoral
      condyle (MFC) and medial tibial plateau (MTP) cartilage was scored using the
      modified Outerbridge scale. Periarticular osteophytosis (PAO) and injury to the
      medial meniscus were recorded. Data were analyzed using Student's t-tests,
      Wilcoxon rank-sum test, and Fisher's exact test for changes in the stifle based
      on meniscal condition, body weight, and duration of lameness. RESULTS: PAO, MFC,
      and MTP articular cartilage scores were not significantly different in dogs with
      or without BHT. There were no significant differences in MFC or MTP scores when
      dogs were evaluated based on bodyweight and the presence or absence of a BHT.
      However, PAO formation was significantly increased in dogs weighing >13.6 kg and
      concurrent meniscal injury vs. dogs weighing <13.6 kg and concurrent meniscal
      injury (P < .001). Significantly more stifles with chronic lameness (40 of 89;
      44.9%) had the highest PAO score of 2 reported compared to only 42 of 182 stifles
      (23.1%) with acute lameness (P < .001). CONCLUSION: The presence of a BHT of the
      medial meniscus was not associated with more severe arthroscopic articular
      cartilage lesions in the medial joint compartment at the time of surgery.

PMID- 27893159
TI  - Modified technique for common carotid artery transposition in standing horses.
AB  - OBJECTIVE: To describe a modified technique for permanent translocation of the
      common carotid artery (CCA) to a subcutaneous position in standing horses. STUDY
      DESIGN: Experimental study. ANIMALS: Healthy adult Standardbred and Warmblood
      horses (n = 8). METHODS: Surgery was performed with the horses standing under
      sedation and with local anesthesia. A combination of previously described
      techniques was used modifying the approach and closure of the incision. The right
      CCA was approached through a linear skin incision dorsal and parallel to the
      jugular vein and through the brachiocephalicus and omohyoideus muscles. The
      artery was dissected free of its sheath and elevated to the skin incision with
      Penrose drains. The brachiocephalicus muscle was sutured in two layers underneath
      the artery leaving it in a subcutaneous position. The horses were allowed to heal
      for 3 weeks prior to catheterization of the artery. RESULTS: The transposed CCA
      was successfully used for repeated catheterization in six of eight horses for a
      period of 10 weeks. None of the horses had intraoperative complications. Two
      horses developed mild peri-incisional edema that resolved spontaneously. Right
      sided laryngeal hemiplegia was observed endoscopically in two horses
      postoperatively. Two horses developed complications (surgical site infection and
      excessive periarterial fibrosis) that compromised the patency of the CCA and
      precluded catheterization. CONCLUSION: Permanent translocation of the CCA in
      standing horses was successful in six out of eight horses. Upper airway endoscopy
      postoperatively may be warranted as laryngeal hemiplegia may ensue.

PMID- 27893160
TI  - Integrating Household Risk Mitigation Behavior in Flood Risk Analysis: An Agent
      Based Model Approach.
AB  - Recent studies showed that climate change and socioeconomic trends are expected
      to increase flood risks in many regions. However, in these studies, human
      behavior is commonly assumed to be constant, which neglects interaction and
      feedback loops between human and environmental systems. This neglect of human
      adaptation leads to a misrepresentation of flood risk. This article presents an
      agent-based model that incorporates human decision making in flood risk analysis.
      In particular, household investments in loss-reducing measures are examined under
      three economic decision models: (1) expected utility theory, which is the
      traditional economic model of rational agents; (2) prospect theory, which takes
      account of bounded rationality; and (3) a prospect theory model, which accounts
      for changing risk perceptions and social interactions through a process of
      Bayesian updating. We show that neglecting human behavior in flood risk
      assessment studies can result in a considerable misestimation of future flood
      risk, which is in our case study an overestimation of a factor two. Furthermore,
      we show how behavior models can support flood risk analysis under different
      behavioral assumptions, illustrating the need to include the dynamic adaptive
      human behavior of, for instance, households, insurers, and governments. The
      method presented here provides a solid basis for exploring human behavior and the
      resulting flood risk with respect to low-probability/high-impact risks.

PMID- 27893161
TI  - Elevated CO2 plus chronic warming reduce nitrogen uptake and levels or activities
      of nitrogen-uptake and -assimilatory proteins in tomato roots.
AB  - Atmospheric CO2 enrichment is expected to often benefit plant growth, despite
      causing global warming and nitrogen (N) dilution in plants. Most plants primarily
      procure N as inorganic nitrate (NO3- ) or ammonium (NH4+ ), using membrane
      localized transport proteins in roots, which are key targets for improving N use.
      Although interactive effects of elevated CO2 , chronic warming and N form on N
      relations are expected, these have not been studied. In this study, tomato
      (Solanum lycopersicum) plants were grown at two levels of CO2 (400 or 700 ppm)
      and two temperature regimes (30 or 37 degrees C), with NO3- or NH4+ as the N
      source. Elevated CO2 plus chronic warming severely inhibited plant growth,
      regardless of N form, while individually they had smaller effects on growth.
      Although %N in roots was similar among all treatments, elevated CO2 plus warming
      decreased (1) N-uptake rate by roots, (2) total protein concentration in roots,
      indicating an inhibition of N assimilation and (3) shoot %N, indicating a
      potential inhibition of N translocation from roots to shoots. Under elevated CO2
      plus warming, reduced NO3- -uptake rate per g root was correlated with a decrease
      in the concentration of NO3- -uptake proteins per g root, reduced NH4+ uptake was
      correlated with decreased activity of NH4+ -uptake proteins and reduced N
      assimilation was correlated with decreased concentration of N-assimilatory
      proteins. These results indicate that elevated CO2 and chronic warming can act
      synergistically to decrease plant N uptake and assimilation; hence, future global
      warming may decrease both plant growth and food quality (%N).

PMID- 27893162
TI  - Late-onset combined immune deficiency due to LIGIV mutations in a 12-year-old
      patient.

PMID- 27893163
TI  - Sorafenib and azacitidine as salvage therapy for relapse of FLT3-ITD mutated AML
      after allo-SCT.
AB  - OBJECTIVE: Patients with acute myeloid leukemia (AML) carrying FLT3-ITD mutations
      (FLT3-ITD+) who relapse after allogeneic transplantation (allo-SCT) have a very
      dismal prognosis with the currently available treatment options. METHODS: We
      treated eight patients with FLT3-ITD+ AML who had relapsed in median 91 d (range,
      28-249) following allo-SCT with a combination of the multikinase inhibitor
      sorafenib and the DNA methyltransferase inhibitor azacitidine (Aza). RESULTS:
      Patients received a median of five cycles of Aza (range, 2-9) and sorafenib with
      a median daily dosage of 750 mg (range 400-800) for 129 d (range, 61-221). Six of
      eight patients received donor lymphocyte infusions (DLI) with a median number of
      two DLI per patient (range, 1-4). Following this treatment, four patients (50%)
      achieved a complete remission and three of them a complete molecular remission.
      Median duration of CR was 182 d (range, 158-406), and two patients remain in
      ongoing remission for 406 and 168 d. Median overall survival was 322 d (range,
      108-574 d) with three patients being currently alive. CONCLUSION: Taken together,
      the combination of sorafenib, Aza, and DLI shows promising efficacy and deserves
      further evaluation in larger patient groups.

PMID- 27893165
TI  - Enabling Stakeholder Involvement in Coastal Disaster Resilience Planning.
AB  - Coastal hazards including storm surge, sea-level rise, and cyclone winds continue
      to have devastating effects on infrastructure systems and communities despite
      costly investments in risk management. Risk management has generally not been
      sufficiently focused on coastal resilience, with community stakeholders involved
      in the process of making their coastline, as a system, more resilient to coastal
      storms. Thus, without stakeholder earlier involvement in coastal resilience
      planning for their community, they are frustrated after disasters occur. The U.S.
      National Academies has defined resilience as "the ability to prepare and plan
      for, absorb, recover from, and more successfully adapt to adverse
      events"(National Research Council). This article introduces a methodology for
      enabling stakeholder-involved resilience discussions across physical,
      information, cognitive, and social domains. The methodology addresses the stages
      of resilience-prepare, absorb, recover, and adapt-and integrates performance
      assessment with scenario analysis to characterize disruptions of risk-management
      priorities. The methodology is illustrated through a case study at Mobile Bay,
      Alabama, USA.

PMID- 27893164
TI  - Diagnostic and prognostic value of human prion detection in cerebrospinal fluid.
AB  - OBJECTIVE: Several prion amplification systems have been proposed for detection
      of prions in cerebrospinal fluid (CSF), most recently, the measurements of prion
      seeding activity with second-generation real-time quaking-induced conversion (RT
      QuIC). The objective of this study was to investigate the diagnostic performance
      of the RT-QuIC prion test in the broad phenotypic spectrum of prion diseases.
      METHODS: We performed CSF RT-QuIC testing in 2,141 patients who had rapidly
      progressive neurological disorders, determined diagnostic sensitivity and
      specificity in 272 cases that were autopsied, and evaluated the impact of
      mutations and polymorphisms in the PRNP gene, and type 1 or type 2 human prions
      on diagnostic performance. RESULTS: The 98.5% diagnostic specificity and 92%
      sensitivity of CSF RT-QuIC in a blinded retrospective analysis matched the 100%
      specificity and 95% sensitivity of a blind prospective study. The CSF RT-QuIC
      differentiated 94% of cases of sporadic Creutzfeldt-Jakob disease (sCJD) MM1 from
      the sCJD MM2 phenotype, and 80% of sCJD VV2 from sCJD VV1. The mixed prion type 1
      2 and cases heterozygous for codon 129 generated intermediate CSF RT-QuIC
      patterns, whereas genetic prion diseases revealed distinct profiles for each PRNP
      gene mutation. INTERPRETATION: The diagnostic performance of the improved CSF RT
      QuIC is superior to surrogate marker tests for prion diseases such as 14-3-3 and
      tau proteins, and together with PRNP gene sequencing the test allows the major
      prion subtypes to be differentiated in vivo. This differentiation facilitates
      prediction of the clinicopathological phenotype and duration of the disease-two
      important considerations for envisioned therapeutic interventions. ANN NEUROL
      2017;81:79-92.

PMID- 27893167
TI  - Effects of low-level laser therapy on burning mouth syndrome.
AB  - To investigate low-level laser therapy (LLLT) applied to treat burning mouth
      syndrome (BMS). This prospective, comparative, partially blinded, single-centre,
      clinical trial of GaAlAs Laser, with 815 nm wavelength, included 44 BMS patients
      divided randomly into three groups: Group I (n = 16): GaAlAs laser 815 nm
      wavelength, 1 W output power, continuous emissions, 4 s, 4 J and fluence rate
      133.3 J cm-2 ; Group II (n = 16): GaAlAs infrared laser, 815 nm wavelength, 1 W
      output power, continuous emissions, 6 s, 6 J and fluence rate 200 J cm-2 ; Group
      III (n = 12) placebo group, sham laser. All groups received a weekly dose for 4
      weeks. Pain intensity was recorded using a 10-cm visual analogue scale; patients
      responded to the oral health impact profile (OHIP-14), xerostomia severity test
      and the hospital anxiety-depression scale (HAD). These assessments were performed
      at baseline, 2 and 4 weeks. LLLT decreased pain intensity and improved OHIP-14
      scores significantly from baseline to 2 weeks in groups I and II compared with
      the placebo group. No statistically significant differences were found from 2 to
      4 weeks. Overall improvements in visual analogue scale (VAS) scores from baseline
      to the end of treatment were as follows: Group I 15.7%; Group II 15.6%; Group III
      placebo 7.3%. LLLT application reduces symptoms slightly in BMS patients.

PMID- 27893166
TI  - The association between parental consanguinity and primary immunodeficiency
      diseases: A systematic review and meta-analysis.
AB  - BACKGROUND: We aimed to establish the prevalence of parental consanguinity among
      patients with primary immunodeficiency diseases (PID) and compare the prevalence
      with the general population. METHOD: We searched PubMed, EMBASE, and Scopus for
      studies mentioning parental consanguinity prevalence in patients with PID and
      calculated the prevalence odds ratio (POR) of parental consanguinity in each
      study, compared to a matched healthy population. RESULTS: We identified 21
      eligible studies with a total population of 18091 accounting for sample overlap.
      The POR among studies on a sample of mixed patients with PID ranged from 0.6 to
      21.9 with the pooled POR of 3.0 (p < 0.001; I2 = 89%, 95% CI: 2.5-3.7).
      CONCLUSION: PIDs with an autosomal recessive pattern of inheritance had
      significant odds of parental consanguinity compared to the healthy population, a
      phenomenon not observed in other inheritance patterns. Determining the extent of
      the impact that consanguinity imposes upon the progeny paves the way for
      convincing healthcare policymakers in highly consanguineous communities to act
      more diligently in informing the masses about the consequences of practicing
      inbreeding.

PMID- 27893169
TI  - Reinforcement in removable prosthodontics: a literature review.
AB  - Removable prosthodontics are often associated with mechanical troubles in daily
      use, such as fracture or deformation. These troubles render prostheses unusable
      and reduce wearers' QOL. Various reinforcements are used to prevent such
      problems, but consensus on reinforcement has not been reached. This review aimed
      to summarise the effects of reinforcement and to propose favourable reinforcement
      based on material, design and position in the prostheses. Initially, 139 articles
      were selected by electronic and manual searches. After exclusion of 99 articles
      based on the exclusion criteria, 40 articles were finally included in the review.
      Electronic searches were performed for articles published from 2005 to 2015 in
      PubMed, EMBASE, MEDLINE and Cochrane Library, and manual searches were performed
      in 10 journals relevant to the topic of removable prosthodontics. For in vitro
      studies, certain dental alloys and fibres were mainly used. Their forms were
      different, including complicated forms in dental alloys and various forms in
      fibres. The materials were examined for mechanical properties like fracture
      strength, flexural strength and elastic modulus and compared with one another or
      without reinforcement. There were a few clinical studies and one longitudinal
      study. Cast metal reinforcement seemed to be most favourable in terms of fracture
      toughness and stiffness. The most favourable forms differed depending on the
      prostheses, but placement around thin and deformable areas was effective.
      However, randomised or longitudinal clinical reports and comparative clinical
      studies on the use of reinforcement were still lacking and such studies are
      necessary in the future.

PMID- 27893168
TI  - Not every patient needs a triglyceride check, but all can get pancreatitis: a
      systematic review and clinical characterization of isotretinoin-associated
      pancreatitis.
AB  - Monitoring of triglycerides for patients on isotretinoin is practised primarily
      to avoid hypertriglyceridaemia-associated pancreatitis. The aim of this study was
      to describe clinically the published cases of hypertriglyceride-associated
      pancreatitis. A comprehensive search strategy using MEDLINE, Embase and grey
      literature was conducted (1960 to January 2016) to identify all case reports of
      isotretinoin-associated pancreatitis and all relevant studies of isotretinoin and
      triglycerides for any indication (>= 20 patients). Terms related to isotretinoin,
      triglycerides and pancreatitis were searched with all available synonyms. Any
      studies that used isotretinoin and mentioned triglycerides or pancreatitis were
      searched in full text, where available, for cases of pancreatitis. Studies from
      all countries and published in any language were included, but Korean and Turkish
      studies could not be analysed. Two authors independently reviewed the
      publications to determine eligibility, and for data extraction. In total, 125
      papers fulfilled the inclusion criteria and were searched for cases of
      pancreatitis. Eleven papers with 25 cases of pancreatitis associated with
      isotretinoin were identified; four of these cases were likely due to
      hypertriglyceridaemia. Three patients had elevated baseline triglycerides, but no
      monitoring. Pancreatitis occurred 6 and 7 weeks, and 6 months after initiation of
      therapy. For the fourth patient who was treated for glioblastoma and died, no
      detailed clinical information was available. Idiosyncratic pancreatitis
      associated with isotretinoin is the most frequent pancreatitis on isotretinoin,
      and patients should be warned about it. Hypertriglyceride-associated pancreatitis
      is an exceedingly rare adverse event of isotretinoin therapy. Our data cannot
      give a frequency or risk for either adverse event. Based on the clinical
      information of the patients available, we conclude that for patients without
      elevated baseline triglycerides, or risk thereof, monitoring of triglycerides
      during therapy is of little value.

PMID- 27893171
TI  - Salvage therapy in first relapse: a retrospective study in a large patient
      population with multiple myeloma.
AB  - OBJECTIVE: There is no strong evidence to guide therapeutic approach to multiple
      myeloma (MM) patients who experience first relapse. The treatment choice can be
      difficult since currently all patients are exposed to novel agents as
      thalidomide, bortezomib and lenalidomide. METHODS: In this retrospective
      analysis, we evaluated the best therapeutic sequence, the role of retreatment,
      and the most beneficial cutoff of first remission in order to choose retreatment,
      analyzing 476 patients relapsed after first-line therapy. RESULTS: Bortezomib
      based regimens upfront followed by lenalidomide-based regimens at first relapse
      resulted in significantly better second progression-free survival (2ndPFS), PFS2,
      and overall survival (OS) compared to the opposite sequence. Changing therapy
      resulted in significantly better 2ndPFS in the whole population, whereas PFS2 was
      significantly longer only in patients who underwent maintenance therapy.
      Moreover, until PFS1 was shorter than 27 months, changing therapy at first
      relapse significantly extended 2ndPFS and PFS2 compared to retreatment, whereas
      similar outcomes were observed between the two strategies, when PFS1 was longer
      than 27 months. CONCLUSION: Lacking randomized trials, our study could help to
      choose the most appropriate therapy algorithm in patients with MM.

PMID- 27893170
TI  - Safety profiles of iron chelators in young patients with haemoglobinopathies.
AB  - BACKGROUND: This review describes the safety of deferoxamine (DFO), deferiprone
      (DFP), deferasirox (DFX) and combined therapy in young patients less than 25 yr
      of age with haemoglobinopathies. METHODS: Searches in electronic literature
      databases were performed. Studies reporting adverse events associated with iron
      chelation therapy were included. Study and reporting quality was assessed using
      AHRQ Risk of Bias Assessment Tool and McMaster Quality Assessment Scale of Harms.
      Prospective clinical studies were pooled in a random-effects meta-analysis of
      proportions. RESULTS: Safety data of 2040 patients from 34 studies were included.
      Ninety-two case reports of 246 patients were identified. DFX (937 patients) and
      DFP (667 patients) possess the largest published safety evidence. Fewer studies
      on combination regimens are available. Increased transaminases were seen in all
      regimens (3.9-31.3%) and gastrointestinal disorders with DFP and DFX (3.7-18.4%
      and 5.8-18.8%, respectively). Therapy discontinuations due to adverse events were
      low (0-4.1%). Reporting quality was selective and poor in most of the studies.
      CONCLUSION: Iron chelation therapy is generally safe in young patients, and
      published data correspond to summary of product characteristics. Each iron
      chelation regimen has its specific safety risks. DFO seems not to be associated
      with serious adverse effects in recommended doses. In DFP and DFX, rare, but
      serious, adverse reactions can occur. Data on combined therapy are scarce, but it
      seems equally safe compared to monotherapy.

PMID- 27893172
TI  - Anthropometrics and prognosis in diffuse large B-cell lymphoma: a multicentre
      study of 653 patients.
AB  - OBJECTIVE: The impact of body mass index (BMI) and body surface area (BSA) on
      survival in diffuse large B-cell lymphoma (DLBCL) is controversial. Recent
      studies show superior outcomes for overweight and obese patients. PATIENTS AND
      METHODS: A total of 653 R-CHOP(-like)-treated DLBCL patients were included in
      this retrospective cohort study. Patients, baseline clinicopathologic
      characteristics and treatment information were retrieved from the Danish Lymphoma
      Registry. Anthropometric measures were obtained from chemotherapy prescription
      charts. RESULTS: Underweight (BMI <18.5 kg/m2 ) was associated with significantly
      worse progression-free survival (PFS) for male patients only in sex-stratified
      analyses (HR 3.92, 95% CI: 1.57-9.75, P = 0.003, for males; HR 1.65, 95% CI: 0.90
      3.02, P = 0.107, for females). In multivariate analyses, underweight was
      associated with worse PFS for both sexes (HR 5.34, 95% CI: 2.07-13.79, P = 0.001,
      for males; HR 2.14, 95% CI: 1.12-4.08, P = 0.021, for females). Similar results
      were obtained in analyses of overall survival. In crude analyses, BSA <1.8 m2 was
      associated with worse PFS for men and women (HR 1.65, 95% CI: 1.03-2.65, P =
      0.039, for men; HR 1.62, 95% CI: 1.03-2.56, P = 0.037, for women). In
      multivariate analyses, however, these associations diminished. CONCLUSIONS: Our
      study demonstrates that underweight DLBCL patients have worse outcomes following
      R-CHOP as compared to normal as well as overweight patients.

PMID- 27893173
TI  - bmp15l, figla, smc1bl, and larp6l are preferentially expressed in germ cells in
      Atlantic salmon (Salmo salar L.).
AB  - Atlantic salmon is a valuable commercial aquaculture species that would benefit
      economically and environmentally by controlling precocious puberty and preventing
      escapees from reproducing with wild populations. One solution to both these
      challenges is the production of sterile individuals by inhibiting the formation
      of germ cells, but achieving this requires more information on the specific
      factors that control germ cell formation. Here, we identified and characterized
      novel factors that are preferentially expressed in Atlantic salmon germ cells by
      screening for gonad-specific genes using available adult multi-tissue
      transcriptomes. We excluded genes with expression in tissues other than gonads
      based on quantity of reads, and then a subset of genes was selected for
      verification in a multi-tissue PCR screen. Four gonad-specific genes (bmp15l,
      figla, smc1bl, and larp6l) were chosen for further characterization, namely: germ
      cell specificity, investigated by comparing mRNA abundance in wild-type and germ
      cell-free gonads by quantitative real-time PCR, and cellular location, visualized
      by in situ hybridization. All four genes were expressed in both testis and ovary,
      and preferentially within the germ cells of both sexes. These genes may be
      essential players in salmon germ cell development, and could be important for
      future studies aiming to understand and control reproduction. Mol. Reprod. Dev.
      84: 76-87, 2017. (c) 2016 Wiley Periodicals, Inc.

PMID- 27893174
TI  - Is there a relationship between objectively measured cognitive changes in
      patients with solid tumours undergoing chemotherapy treatment and their health
      related quality of life outcomes? A systematic review.
AB  - BACKGROUND: This systematic review examines whether there is a relationship
      between objective measures of chemotherapy-related cognitive impairment in
      patients with solid cancer tumours and health-related quality of life (HRQoL).
      METHODS: Multiple online databases were searched (including Ovid MEDLINE, EMBASE,
      PsycINFO, PsycARTICLES, CINAHL, PubMed, and Web of Science) to identify articles
      published between 1980 and 2016 examining the extent of chemotherapy-related
      cognitive deficit and its relationship with HRQoL in cancer patients. Of 2769
      potentially relevant articles, 17 studies met the inclusion criteria for the
      current review. RESULTS: Evidence for the presence of cognitive impairment in
      patients treated with chemotherapy was found in 15 of the 17 studies. Of the 15
      studies finding some sort of cognitive impairment, 12 were in female breast
      cancer patients, 2 in bowel cancer, and 1 each in ovarian and lung cancer. Three
      of the 15 studies found a significant relationship between various objectively
      measured cognitively impaired domains and specific HRQoL outcomes. There was,
      however, only limited testing of the relationships between quantifiable cognitive
      dysfunction and HRQoL domains. CONCLUSIONS: This review suggests that in patients
      with solid tumours, where there is a relationship between chemotherapy treatment
      and cognitive impairment, the type and level of cognitive decline does not
      consistently appear to affect such patients' HRQoL. This could be partly
      explained by variations in study design, measures used, definitions of cognitive
      impairment, varying measurement time frames, small sample sizes, and differences
      in disease severity and type of treatment regimes.

PMID- 27893175
TI  - Noble-Metal-Free Hybrid Membranes for Highly Efficient Hydrogen Evolution.
AB  - Free-standing and flexible WS2 /WO2.9 /C hybrid membranes are synthesized and
      used as catalytic electrodes for electrochemical hydrogen evolution, exhibiting a
      high and stable catalytic activity. By virtue of the synergetic effect, a low
      onset overpotential of 20 mV and a Tafel slope of 36 mV dec-1 are achieved.

PMID- 27893176
TI  - Desmopressin for treatment of platelet dysfunction and reversal of antiplatelet
      agents: a systematic review and meta-analysis of randomized controlled trials.
AB  - : Essentials The optimal management of patients with platelet dysfunction
      undergoing surgery is unclear. This meta-analysis compared perioperative
      administration of desmopressin to placebo. Desmopressin reduced red cell
      transfusions, blood loss and risk of re-operation due to bleeding. There were too
      few events to determine if there was a change in the risk of thrombotic events.
      SUMMARY: Background Platelet dysfunction, including that caused by antiplatelet
      agents, increases the risk of perioperative bleeding. The optimal management of
      patients with platelet dysfunction undergoing surgery is unclear. Objectives To
      assess whether desmopressin reduces perioperative allogeneic red cell transfusion
      and bleeding in patients with platelet dysfunction. Patients/Methods We searched
      for randomized controlled trials in The Cochrane Central Register of Controlled
      Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and the ISI Web
      of Science to 7th July 2016. Data were pooled using mean difference (MD),
      relative risks or Peto odds ratios (pOR) using a random-effects model. Results
      Ten trials with 596 participants were identified, all in the setting of cardiac
      surgery. Platelet dysfunction was due to antiplatelet agents in six trials and
      cardiopulmonary bypass in four trials. Patients treated with desmopressin were
      transfused with fewer red cells (MD, -0.65 units; 95% Confidence Interval [CI], 
      1.16 to -0.13 units), lost less blood (MD, -253.93 mL; 95% CI, -408.01 to -99.85
      mL) and had a lower risk of re-operation due to bleeding (pOR, 0.39; 95% CI, 0.18
      0.84). The GRADE quality of evidence was very low to moderate, suggesting
      considerable uncertainty over the results Conclusions Desmopressin may be a
      useful agent to reduce bleeding and transfusion requirements for people with
      platelet dysfunction or with a history of recent antiplatelet drug administration
      undergoing cardiac surgery.

PMID- 27893177
TI  - Efficient Charge Transfer and Fine-Tuned Energy Level Alignment in a THF
      Processed Fullerene-Free Organic Solar Cell with 11.3% Efficiency.
AB  - Fullerene-free organic solar cells show over 11% power conversion efficiency,
      processed by low toxic solvents. The applied donor and acceptor in the bulk
      heterojunction exhibit almost the same highest occupied molecular orbital level,
      yet exhibit very efficient charge creation.

PMID- 27893178
TI  - Comprehensive genetic characterization of rosette-forming glioneuronal tumors:
      independent component analysis by tissue microdissection.
AB  - A rosette-forming glioneuronal tumor (RGNT) is a rare mixed neuronal-glial tumor
      characterized by biphasic architecture of glial and neurocytic components. The
      number of reports of genetic analyses of RGNTs is few. Additionally, the genetic
      background of the unique biphasic pathological characteristics of such mixed
      neuronal-glial tumors remains unclear. To clarify the genetic background of
      RGNTs, we performed separate comprehensive genetic analyses of glial and
      neurocytic components of five RGNTs, by tissue microdissection. Two missense
      mutations in FGFR1 in both components of two cases, and one mutation in PIK3CA in
      both components of one case, were detected. In the latter case with PIK3CA
      mutation, the additional FGFR1 mutation was detected only in the glial component.
      Moreover, the loss of chromosome 13q in only the neurocytic component was
      observed in one other case. Their results suggested that RGNTs, which are tumors
      harboring two divergent differentiations that arose from a single clone, have a
      diverse genetic background. Although previous studies have suggested that RGNTs
      and pilocytic astrocytomas (PAs) represent the same tumor entity, their results
      confirm that the genetic background of RGNTs is not identical to that of PA.

PMID- 27893179
TI  - CtrA controls cell division and outer membrane composition of the pathogen
      Brucella abortus.
AB  - Brucella abortus is a pathogen infecting cattle, able to survive, traffic, and
      proliferate inside host cells. It belongs to the Alphaproteobacteria, a
      phylogenetic group comprising bacteria with free living, symbiotic, and
      pathogenic lifestyles. An essential regulator of cell cycle progression named
      CtrA was described in the model bacterium Caulobacter crescentus. This regulator
      is conserved in many alphaproteobacteria, but the evolution of its regulon
      remains elusive. Here we identified promoters that are CtrA targets using ChIP
      seq and we found that CtrA binds to promoters of genes involved in cell cycle
      progression, in addition to numerous genes encoding outer membrane components
      involved in export of membrane proteins and synthesis of lipopolysaccharide.
      Analysis of a conditional B. abortus ctrA loss of function mutant confirmed that
      CtrA controls cell division. Impairment of cell division generates elongated and
      branched morphologies, that are also detectable inside HeLa cells. Surprisingly,
      abnormal bacteria are able to traffic to the endoplasmic reticulum, the usual
      replication niche of B. abortus in host cells. We also found that CtrA depletion
      affected outer membrane composition, in particular the abundance and spatial
      distribution of Omp25. Control of the B. abortus envelope composition by CtrA
      indicates the plasticity of the CtrA regulon along evolution.

PMID- 27893180
TI  - Hybrid crosses and the genetic basis of interspecific divergence in lifespan in
      Pristionchus nematodes.
AB  - Characterizing the genetic basis of among-species variation in lifespan is a
      major goal of evolutionary gerontology research, but the very feature that
      defines separate species - the inability to interbreed - makes achieving this
      goal impractical, if not impossible, for most taxa. Pristionchus nematodes
      provide an intriguing system for tackling this problem, as female lifespan varies
      among species that can be crossed to form viable (although infertile) hybrids. By
      conducting reciprocal crosses among three species - two dioecious (long-lived
      Pristionchus exspectatus and short-lived Pristionchus arcanus) and one
      androdioecious (short-lived Pristionchus pacificus) - we found that female
      lifespan was long for all hybrids, consistent with the hypothesis that the
      relatively short lifespans seen for P. pacificus hermaphrodites and P. arcanus
      females are caused by independent, recessive alleles that are masked in hybrid
      genomes. Cross-direction had a small effect on survivorship for crosses involving
      P. exspectatus, indicating that nuclear-mitochondrial interactions may also
      influence Pristionchus longevity. Our findings suggest that long lifespan in P.
      exspectatus reflects the realization of an ancestral potential for extended
      longevity in the P. pacificus species complex. This work demonstrates the utility
      of interspecific hybrids for ageing research and provides a foundation for future
      work on the genetic architecture of interspecific lifespan variation.

PMID- 27893181
TI  - Synaesthesia lost and found: two cases of person- and music-colour synaesthesia.
AB  - Synaesthesia is a developmental condition involving cross-communication between
      sensory modalities or substreams whereby an inducer (e.g. a sound) automatically
      evokes a concurrent percept in another modality (e.g. a colour). Whether this
      condition arises due to atypical structural connectivity (e.g., between normally
      unconnected cortical areas) or altered neurochemistry remains a central question.
      We report the exceptional cases of two synaesthetes - subjects AB and CD - both
      of whom experience coloured auras around individuals, as well as coloured
      perceptions in response to music. Both subjects have, in recent years, suffered a
      complete loss or reduction of their synaesthetic experiences, one (AB) through
      successive head traumas, including a lightning strike, followed by a number of
      medications, and the other (CD) while taking anxiolytic medications. Using semi
      structured interviews and data from the Synaesthesia Battery and a colourpicker
      task, we characterize the phenomenological characteristics of their pre-loss
      synaesthesia, as well as the subsequent restoration of each subject's
      synaesthetic experiences (in the months post-trauma for AB, and after cessation
      of medication for CD). Even after years of suppression, the patterns of
      associations were highly consistent with those experienced pre-injury. The
      phenomenological experience of synaesthesia can, thus, like most conscious
      experiences, be modulated by pharmacologically diverse medications or head
      injury. However, the underlying neural substrates mediating specific synaesthetic
      pairings appear remarkably 'hard-wired' and can persist over very long periods
      even under conditions that alter or completely suppress the conscious
      synaesthetic experience itself.

PMID- 27893182
TI  - Interindividual variability in dabigatran and rivaroxaban exposure: contribution
      of ABCB1 genetic polymorphisms and interaction with clarithromycin.
AB  - : Essentials Rivaroxaban and dabigatran are substrates of the P-glycoprotein (P
      gp) encoded by the ABCB1 gene. We tested the effect of ABCB1 polymorphisms and of
      a P-gp inhibitor on both drugs' pharmacokinetics. The ABCB1 genotype was not a
      clinically relevant determinant of both drugs' pharmacokinetics. Administration
      of P-gp inhibitors with dabigatran or rivaroxaban should be exercised with
      caution. SUMMARY: Background The direct oral anticoagulants (DOACs) dabigatran
      and rivaroxaban are both substrates of the P-glycoprotein (P-gp) transporter,
      encoded by the ABCB1 gene. Rivaroxaban is metabolized by cytochrome P450 A4
      (CYP3A4). Interindividual variability in DOAC exposure and frequent P-gp
      associated drug-drug interactions have been described in patients. Objective To
      assess the influence of ABCB1 polymorphisms on the pharmacokinetics of dabigatran
      and rivaroxaban, associated or not with clarithromycin, a P-gp and CYP3A4
      inhibitor. Methods Sixty healthy male volunteers, selected according to ABCB1
      genotype (20 homozygous mutated, 20 heterozygous mutated, and 20 wild-type for
      haplotype 2677-3435), were included in this randomized, two-center, crossover
      study. All received sequentially a single dose of dabigatran etexilate (300 mg)
      and rivaroxaban (40 mg) associated or not with clarithromycin. Peak plasma
      concentration and area under the curve (AUC) were compared across the three ABCB1
      genotypes. The effect of clarithromycin on dabigatran or rivaroxaban
      pharmacokinetics was assessed. Results Interindividual coefficients of variation
      for AUC were 77% for dabigatran and 51% for rivaroxaban. ABCB1 genotype did not
      significantly affect drug pharmacokinetics: AUC ratios between mutant-allele
      carriers and wild-type volunteers were 1.27 (95% confidence interval [CI] 0.84
      1.92) and 1.20 (95% CI 0.96-1.51) for dabigatran and rivaroxaban, respectively.
      Clarithromycin coadministration led to a two-fold increase in both drugs' AUC,
      irrespective of ABCB1 genotype: ratios of geometric means were 2.0 (95% CI 1.15
      3.60) and 1.94 (95% CI 1.42-2.63) for dabigatran and rivaroxaban, respectively.
      Conclusions ABCB1 genotype is not a significant determinant of interindividual
      variability in dabigatran and rivaroxaban pharmacokinetics. The levels of one
      drug did not predict the levels of the other. Coadministration of a P-gp/CYP3A4
      inhibitor with dabigatran or rivaroxaban may warrant caution in patients at risk
      of overexposure.

PMID- 27893183
TI  - Toxic effects of human and rodent variants of alpha-synuclein in vivo.
AB  - In Parkinson's disease, abnormal alpha-synuclein (asyn) accumulation leads to the
      formation of soluble oligomeric species thought to be toxic to cells as well as
      intraneuronal inclusions. To date, the precise mechanisms leading to aggregation
      of asyn in the brain is not well-understood. Previous studies in yeast,
      drosophila, and transgenic mice suggested that a non-A beta component depleted
      version of human asyn [h-asyn(D70-83)] or human beta-synuclein (h-bsyn),
      naturally lacking this centrally located hydrophobic region, are less prone to
      form aggregates in vitro and are expected to be less toxic compared to h-asyn in
      vivo, although not all experimental studies unequivocally support the latter
      view. To address this outstanding issue, we directly compared the neurotoxicity
      of human asyn against that of h-asyn(D70-83), h-bsyn as well as rat asyn using an
      adeno-associated viral vector to express these proteins in a dose-response study
      where the vector load was varied over two orders of magnitude. By quantifying the
      neurodegeneration of rat substantia nigra dopamine neurons here we show that h
      asyn, h-bsyn, and h-asyn(D70-83) display comparable neurotoxicity across the
      vector doses tested. On the other hand, rat asyn and GFP control vectors
      displayed a different profile, where no detectable neurodegeneration was seen
      except at the highest vector titer. Thus, the two main conclusions of our study
      are that (i) deletion of the central hydrophobic region in h-asyn is not
      sufficient to alter its neurotoxic properties and (ii) expression of the widely
      used GFP control protein can cause measurable neurodegeneration at high titers.

PMID- 27893184
TI  - Electrocardiogram Alterations Associated With Psychotropic Drug Use and CACNA1C
      Gene Variants in Three Independent Samples.
AB  - Several antipsychotics and antidepressants have been associated with QTc
      prolongation or other electrocardiogram (ECG) alterations, but their impact is
      still debated and other risk factors are known to affect QTc. We investigated the
      effect of antidepressants and antipsychotics on QTc and other ECG intervals/waves
      in three samples. Two discovery samples (cross-sectional sample n = 145 and
      prospective sample n = 68, naturalistic treatment) and a replication prospective
      sample (Clinical Antipsychotic Trials of Intervention Effectiveness, n = 515,
      randomized treatment) were analysed. In both prospective samples, baseline/follow
      up changes in ECG parameters were analysed in relation to the number of
      psychotropic drugs stratified according to their known cardiovascular risk. In
      the cross-sectional sample, ECG parameters were compared among drugs with
      different risk profile. The possible effect of single nucleotide polymorphisms
      (SNPs) in the CACNA1C gene on QTc was also investigated. There was no evidence of
      mean QTc prolongation or increased risk of clinically relevant QTc prolongation
      (>=20 msec.) in association with psychotropic drugs stratified according to their
      known cardiovascular risk. The prescription of drugs with cardiovascular risk was
      less common in older individuals or individuals with cardiovascular
      comorbidities. Other factors (gender, baseline QTc, renal function) affected QTc.
      rs1006737 and SNPs in linkage disequilibrium with it modulated QTc
      duration/changes in all samples. An association between risk drugs and shorter RR
      interval or higher heart rate was found in all samples. A relevant effect of
      psychotropic drugs with cardiovascular risk on QTc duration was not observed. A
      number of factors other than psychotropic drugs may influence QTc. CACNA1C
      rs1006737 may modulate QTc in patients treated with psychotropic drugs.

PMID- 27893185
TI  - Women's Pathways to Abortion Care in South Carolina: A Qualitative Study of
      Obstacles and Supports.
AB  - CONTEXT: Women seeking timely and affordable abortion care may face myriad
      challenges, including high out-of-pocket costs, transportation demands,
      scheduling difficulties and stigma. State-level regulations may exacerbate these
      burdens and impede women's access to a full range of care. Women's reports of
      their experiences can inform efforts to improve pathways to abortion care.
      METHODS: In 2014, semistructured qualitative interviews were conducted with 45
      women obtaining abortions in South Carolina, which has a restrictive abortion
      environment. Interviews elicited information about women's pathways to abortion,
      including how they learned about and obtained care, whether they received
      professional referrals, and the supports and obstacles they experienced.
      Transcripts were examined using thematic analysis to identify key themes along
      the pathways, and a process map was constructed to depict women's experiences.
      RESULTS: Twenty participants reported having had contact with a health
      professional or crisis pregnancy center staff for pregnancy confirmation, and
      seven of them received an abortion referral. Women located abortion clinics
      through online searches, previous experience, and friends or family. Financial
      strain was the most frequently cited obstacle, followed by transportation
      challenges. Women reported experiencing emotional strain, stress and stigma, and
      described the value of receiving social support. Because of financial pressures,
      the regulation with the greatest impact was the one prohibiting most insurance
      plans from covering abortion care. CONCLUSIONS: Further research on experiences
      of women seeking abortion services, and how these individuals are affected by
      evolving state policy environments, will help shape initiatives to support
      timely, affordable and safe abortion care in a climate of increasing
      restrictions.

PMID- 27893187
TI  - "To Twist or Not to Twist": Figure-of-Eight and Planar Structures of Octaphyrins.
AB  - Amongst the various porphyrinoids, octaphyrin has attracted significant attention
      owing to its diverse syntheses, conformations, and metal-ligation properties.
      Octaphyrin is a higher homologue of porphyrin and is formed by linking together
      heterocycles such as pyrrole, furan, thiophene, and selenophene through alpha
      alpha or alpha-meso carbon bonds. The planar conformation is mainly achieved
      through inversion of the heterocyclic units from the center of macrocycle;
      avoiding meso-bridges; introducing a para-quinodimethane bridge; employing a neo
      confusion approach; protonation; and by generating dianionic species. In this
      Focus Review, recent synthetic advancements in the field of octaphyrins are
      summarized. The twisted conformation of the octaphyrin binds to two metal ions in
      a tetracoordinate geometry. The diphosphorus complex of octaphyrin represents the
      first example of a stable expanded isophlorin.

PMID- 27893186
TI  - The relative influence of hematocrit and red blood cell velocity on oxygen
      transport from capillaries to tissue.
AB  - OBJECTIVE: Oxygen transport to parenchymal cells occurs mainly at the
      microvascular level and depends on convective RBC flux, which is proportional in
      an individual capillary to the product of capillary hematocrit and RBC velocity.
      This study investigates the relative influence of these two factors on tissue PO2
      . METHODS: A simple analytical model is used to quantify the respective
      influences of hematocrit, RBC velocity, and RBC flow on tissue oxygenation around
      capillaries. Predicted tissue PO2 levels are compared with a detailed
      computational model. RESULTS: Hematocrit is shown to have a larger influence on
      tissue PO2 than RBC velocity. The effect of RBC velocity increases with distance
      from the arterioles. Good agreement between analytical and numerical results is
      obtained, and the discrepancies are explained. Significant dependence of MTCs on
      RBC velocity at low hematocrit is demonstrated. CONCLUSIONS: For a given RBC flux
      in a capillary, the PO2 in the surrounding tissue increases with increasing
      hematocrit, as a consequence of decreasing IVR to diffusive oxygen transport from
      RBCs to tissue. These results contribute to understanding the effects of blood
      flow changes on oxygen transport, such as those that occur in functional
      hyperemia in the brain.

PMID- 27893188
TI  - DEK oncogene is overexpressed during melanoma progression.
AB  - DEK is an oncoprotein involved in a variety of cellular functions, such as DNA
      repair, replication, and transcriptional control. DEK is preferentially expressed
      in actively proliferating and malignant cells, including melanoma cell lines in
      which DEK was previously demonstrated to play a critical role in proliferation
      and chemoresistance. Still, the impact of this protein in melanoma progression
      remains unclear. Thus, we performed a comprehensive analysis of DEK expression in
      different melanocytic tumors. The immunostaining results of 303 tumors
      demonstrated negligible DEK expression in benign lesions. Conversely, malignant
      lesions, particularly in metastatic cases, were largely positive for DEK
      expression, which was partially associated with genomic amplification.
      Importantly, DEK overexpression was correlated with histological features of
      aggressiveness in primary tumors and poor prognosis in melanoma patients. In
      conclusion, our study provides new insight into the involvement of DEK in
      melanoma progression, as well as proof of concept for its potential application
      as a marker and therapeutic target of melanoma.

PMID- 27893189
TI  - A first population-based long-term outcome study in adults with repaired
      tetralogy of Fallot in Malta.
AB  - OBJECTIVES: To determine overall and reintervention-free survival for repaired
      Maltese tetralogy of Fallot patients and to investigate the potential impact of
      gender, age at repair, genetic syndromes, previous palliation, and type of repair
      on these outcomes. DESIGN: All 130 tetralogy of Fallot patients born before the
      end of 1997 included in the local database were extracted. Surgical repair type,
      age at repair and operative survival were analyzed among the 103/130 repaired
      patients. Kaplan-Meier survival analyses were performed on the 75 repair
      survivors with complete follow-up data (mean follow-up 26.37 +/- 9.27 (range 9.95
      51.21) years). RESULTS: Patients born after 1985 were operated at a younger age
      (median 1.28 years) compared with patients born before 1985 (median 9.64 years)
      (P < .001). Transannular patch repair was the commonest operation among patients
      born after 1985 (43.90%), while repair without transannular patch use prevailed
      among those born before 1985 (66.13%). 90.24% of patients born after 1985
      survived reparative surgery compared with 70.37% of those born before 1985. Of
      the 75 repair survivors, 7 (9.33%) died of cardiac causes and 22 (29.33%) needed
      reintervention during follow-up. Overall estimated mean survival was 45.56 years
      (95% CI 41.67-49.24) with estimated survival rate of 77.5% at 40 years from
      repair. Estimated mean reintervention-free survival was 37.71 years (95% CI 33.75
      41.66) with estimated reintervention-free survival rate of 59.2% at 40 years.
      Patients with genetic syndromes had significantly lower overall survival after
      repair. Transannular patch repair was associated with significantly lower
      reintervention-free survival (median 32.37 years (95% CI 12.75-51.99)) compared
      with repair without transannular patch [median 44.21 years (95% CI 43.06-45.35);
      P = .03]. CONCLUSIONS: Although survival after tetralogy of Fallot repair in
      contemporary patients is very good, cardiac death can occur at any stage and
      structural reintervention is common. Regular follow-up with imaging and rhythm
      monitoring remains of utmost importance in all patients.

PMID- 27893190
TI  - A High-Performance Lithium-Ion Capacitor Based on 2D Nanosheet Materials.
AB  - Lithium-ion capacitors (LICs) are promising electrical energy storage systems for
      mid-to-large-scale applications due to the high energy and large power output
      without sacrificing long cycle stability. However, due to the different energy
      storage mechanisms between anode and cathode, the energy densities of LICs often
      degrade noticeably at high power density, because of the sluggish kinetics
      limitation at the battery-type anode side. Herein, a high-performance LIC by well
      defined ZnMn2 O4 -graphene hybrid nanosheets anode and N-doped carbon nanosheets
      cathode is presented. The 2D nanomaterials offer high specific surface areas in
      favor of a fast ion transport and storage with shortened ion diffusion length,
      enabling fast charge and discharge. The fabricated LIC delivers a high specific
      energy of 202.8 Wh kg-1 at specific power of 180 W kg-1 , and the specific energy
      remains 98 Wh kg-1 even when the specific power achieves as high as 21 kW kg-1 .

PMID- 27893191
TI  - Young Investigator Challenge: Molecular testing in noninvasive follicular thyroid
      neoplasm with papillary-like nuclear features.
AB  - BACKGROUND: Molecular testing provides an important ancillary study for thyroid
      nodules with indeterminate cytology. The nomenclature shift to "noninvasive
      follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) will
      impact the performance of molecular tests. For the current study, the authors
      reviewed the performance of the Afirma gene-expression classifier (GEC) and the
      University of Pittsburgh Medical Center (UPMC) targeted mutation panel tests in
      thyroid nodules that were subsequently diagnosed as NIFTP on surgical resection.
      METHODS: In total, 302 nodules were sent for molecular testing between June 2012
      and June 2016. These cases were retrospectively reviewed to identify patients who
      underwent subsequent surgical resection and were diagnosed with follicular
      variant of papillary thyroid carcinoma (FVPTC). Twenty-five nodules that were
      diagnosed as FVPTC met the initial inclusion criteria. These cases were reviewed
      using strict criteria to identify NIFTP. RESULTS: Eight cases met criteria for
      NIFTP, and 4 NIFTPs underwent Afirma testing. Cytology diagnoses were all
      Bethesda category III, with 3 diagnosed as atypia of undetermined significance
      (AUS) and 1 diagnosed as follicular lesion of undetermined significance (FLUS).
      All of these nodules were identified as "suspicious" using GEC. Four NIFTPs
      underwent testing at UPMC, all using ThyroSeq V2. The cytology diagnoses for
      these nodules also were category III, with the exception of 1 nodule that was
      category IV, suspicious for follicular neoplasm. All NIFTPs were positive for
      mutations, all of which were RAS mutations (NRAS, KRAS). One patient who had a
      nodule classified as NIFTP had metastatic carcinoma identified in a lymph node.
      Another who had a 6-cm tumor had coexisting NRAS and TERT mutations. CONCLUSIONS:
      The current results indicate that NIFTP is a rare tumor if defined by strict
      criteria, that both the GEC and UPMC methods indicate abnormalities in NIFTP, and
      further independent study will be needed to better characterize the molecular and
      clinical characteristics of NIFTP. Cancer Cytopathol 2016;124:893-900. (c) 2016
      American Cancer Society.

PMID- 27893192
TI  - Serial cardiac MRIs in adult Fontan patients detect progressive hepatic
      enlargement and congestion.
AB  - BACKGROUND: The progression of hepatic disease in adult Fontan patients is not
      well understood. They reviewed the experience with serial cardiac MRIs (CMR) in
      adult Fontan patients to determine if hepatic anatomic markers of prolonged
      Fontan exposure were present and if clinical predictors of progressive hepatic
      congestion could be identified. METHODS AND RESULTS: A retrospective cohort study
      of all adult Fontan patients who had undergone at least two CMRs was performed.
      Hepatic dimensions, inferior vena cava (IVC) size, right hepatic vein (RHV) size
      and spleen diameter were determined from images acquired at the time of
      clinically guided CMR. Two radiologists with expertise in hepatic imaging graded
      congestion and liver size independently using post-gadolinium contrast sequences.
      Twenty-seven patients met inclusion criteria. Over a mean time of 5.1 years
      between CMRs, there was a significant increase in mean lateral-medial hepatic
      dimension (P = .005), mean RHV diameter (P = .004), and mean splenic diameter (P
      = .001). Serial post-gadolinium imaging was available in 25/27 (93%) patients of
      which 15/27 (55%) showed evidence of progressive hepatic congestion across serial
      studies. Progressive hepatic congestion was associated with single ventricle
      ejection fraction (SVEF) less than 50% (P = .008), and larger indexed end
      diastolic (EDVI) and end-systolic volume (ESVI). RHV diameter was the only
      anatomic variable significantly correlated with time from Fontan completion (P =
      .004). CONCLUSIONS: Serial CMRs detected progressive liver and hepatic vein
      enlargement in our cohort of adult Fontan patients over a mean time of 5.2 years.
      Progressive hepatic congestion occurs in a significant number of adult Fontan
      patients and may be associated with ventricular enlargement and decreased
      ventricular function by CMR.

PMID- 27893193
TI  - The oil-contaminated soil diazotroph Azoarcus olearius DQS-4T is genetically and
      phenotypically similar to the model grass endophyte Azoarcus sp. BH72.
AB  - The genome of Azoarcus olearius DQS-4T , a N2 -fixing Betaproteobacterium
      isolated from oil-contaminated soil in Taiwan, was sequenced and compared with
      other Azoarcus strains. The genome sequence showed high synteny with Azoarcus sp.
      BH72, a model endophytic diazotroph, but low synteny with five non-plant
      associated strains (Azoarcus CIB, Azoarcus EBN1, Azoarcus KH32C, A. toluclasticus
      MF63T and Azoarcus PA01). Average Nucleotide Identity (ANI) revealed that DQS-4T
      shares 98.98% identity with Azoarcus BH72, which should now be included in the
      species A. olearius. The genome of DQS-4T contained several genes related to
      plant colonization and plant growth promotion, such as nitrogen fixation, plant
      adhesion and root surface colonization. In accordance with the presence of these
      genes, DQS-4T colonized rice (Oryza sativa) and Setaria viridis, where it was
      observed within the intercellular spaces and aerenchyma mainly of the roots.
      Although they promote the growth of grasses, the mechanism(s) of plant growth
      promotion by A. olearius strains is unknown, as the genomes of DQS-4T and BH72 do
      not contain genes for indole acetic acid (IAA) synthesis nor phosphate
      solubilization. In spite of its original source, both the genome and behaviour of
      DQS-4T suggest that it has the capacity to be an endophytic, nitrogen-fixing
      plant growth-promoting bacterium.

PMID- 27893195
TI  - Photodynamic therapy for the treatment of atherosclerotic plaque: Lost in
      translation?
AB  - Acute coronary syndrome is a life-threatening condition of utmost clinical
      importance, which, despite recent progress in the field, is still associated with
      high morbidity and mortality. Acute coronary syndrome results from a rupture or
      erosion of vulnerable atherosclerotic plaque with secondary platelet activation
      and thrombus formation, which leads to partial or complete luminal obstruction of
      a coronary artery. During the last decade, scientific evidence demonstrated that
      when an acute coronary event occurs, several nonculprit plaques are in a
      "vulnerable" state. Among the promising approaches, several investigations
      provided evidence of photodynamic therapy (PDT)-induced stabilization and
      regression of atherosclerotic plaque. Significant development of PDT strategies
      improved its therapeutic outcome. This review addresses PDT's pertinence and
      major problems/challenges toward its translation to a clinical reality.

PMID- 27893194
TI  - Incidence, morphology, and progression of bicuspid aortic valve in pediatric and
      young adult subjects with coexisting congenital heart defects.
AB  - BACKGROUND: Bicuspid aortic valve (BAV) occurs both as an isolated cardiac lesion
      and in association with congenital heart defects (CHD). Their aim was to identify
      the incidence and morphology of BAV in patients with coexisting CHD and compare
      their disease progression to patients with isolated BAV. METHODS: The Mayo Clinic
      echocardiography database was retrospectively analyzed to identify pediatric and
      young adult patients (<=22 years) who were diagnosed with BAV from 1990 to 2015.
      The morphology of BAV was determined from the echocardiographic studies before
      any intervention. RESULTS: Overall, 1010 patients with BAV were identified, 619
      (61%) with isolated BAV and 391 (39%) with BAV and coexisting CHD. The incidence
      of BAV was highest in patients with coarctation of the aorta (36%) and
      interrupted aortic arch (36%). In comparison to patients with isolated BAV,
      patients with BAV and left-sided obstructive lesions more frequently had right
      left cusp fusion (P = .0001). BAV in patients with right-sided obstructive
      lesions was rare, but they more frequently had right-noncoronary or left
      noncoronary cusp fusion (P = .01). No significant progression of aortic stenosis
      or regurgitation was observed in patients with BAV and coexisting CHD; however in
      patients with isolated BAV the severity of aortic regurgitation increased with
      age. In patients with isolated BAV, the ascending aorta diameter (z-score)
      increased with age, peaked around 8-9 years of age, and was larger in comparison
      to patients with BAV and coexisting CHD. The sinus of Valsalva diameter (z-score)
      in patients with BAV and ventricular septal defect was larger than isolated BAV
      patients after 18 years (P < .04). CONCLUSIONS: The morphology of BAV, the
      pattern and progression of aortic dilatation, and the severity of aortic valve
      disease vary in pediatric and young adult patients with BAV and coexisting CHD.
      However, there was no significant BAV disease progression when associated with
      these CHD.

PMID- 27893196
TI  - Guiding hMSC Adhesion and Differentiation on Supported Lipid Bilayers.
AB  - Mesenchymal stem cells (MSCs) are intensively investigated for regenerative
      medicine applications due to their ease of isolation and multilineage
      differentiation capacity. Hence, designing instructive microenvironments to guide
      MSC behavior is important for the generation of smart interfaces to enhance
      biomaterial performance in guiding desired tissue formation. Supported lipid
      bilayers (SLBs) as cell membrane mimetics can be employed as biological
      interfaces with easily tunable characteristics such as biospecificity, mobility,
      and density of predesigned ligand molecules. Arg-Gly-Asp (RGD) ligand
      functionalized SLBs are explored for guiding human MSC (hMSC) adhesion and
      differentiation by studying the effect of changes in ligand density and mobility.
      Cellular and molecular analyses show that adhesion occurs through specific
      interactions with RGD ligands where the extent is positively correlated to
      changes in ligand density. Furthermore, cell area is significantly regulated by
      ligand density on ligand-mobile SLBs when compared to ligand-immobile SLBs.
      Finally, the osteogenic differentiation capacity of hMSCs is positively
      correlated to ligand density on ligand-mobile SLBs indicating that regulation of
      cell spreading is linked to cell differentiation capacity. These results
      demonstrate that hMSC behavior can be directed on SLBs by molecular design and
      presents SLBs as versatile platforms for future engineering of smart biomaterial
      coatings.

PMID- 27893197
TI  - Importance to question sinonasal symptoms and to perform rhinoscopy and
      rhinomanometry in cystic fibrosis patients.
AB  - OBJECTIVES: Cystic fibrosis (CF) patients almost regularly reveal sinonasal
      pathology. The purpose of this study was to assess association between objective
      and subjective measurements of sinonasal involvement comparing nasal airflow
      obtained by active anterior rhinomanometry (AAR), nasal endoscopic findings, and
      symptoms assessed with the Sino-Nasal Outcome Test-20 (SNOT-20). METHODS: Nasal
      cavities were explored by anterior rigid rhinoscopy and findings were compared to
      inspiratory nasal airflow measured by AAR to quantify nasal patency and
      subjective health-related quality of life in sinonasal disease obtained with the
      SNOT-20 questionnaire. Relations to upper and lower airway colonization with
      Pseudomonas aeruginosa, medical treatment, and sinonasal surgery were analysed.
      RESULTS: A total of 124 CF patients were enrolled (mean age 19.9 +/- 10.4 years,
      range 4-65 years). A significant association of detection of nasal polyposis (NP)
      in rhinoscopy was found with increased primary nasal symptoms (PNS) which include
      "nasal obstruction," "sneezing," "runny nose," "thick nasal discharge," and
      "reduced sense of smell." At the same time patients with pathologically decreased
      airflow neither showed elevated SNOT-20 scores nor abnormal rhinoscopic findings.
      Altogether, rhinomanometric and rhinoscopic findings are not significantly
      related. CONCLUSIONS: Among SNOT-20 scores the PNS subscore is related to
      rhinoscopically detected polyposis and sinonasal secretion. Therefore, we
      recommend including short questions regarding PNS into CF-routine care. At the
      same time our results show that a high inspiratory airflow is not associated with
      a good sensation of nasal patency. Altogether, rhinomanometry is not required
      within routine CF-care, but it can be interesting as an outcome parameter within
      clinical trials. Pediatr Pulmonol. 2017;52:167-174. (c) 2016 Wiley Periodicals,
      Inc.

PMID- 27893198
TI  - Clinical Application of Ultrasound-Guided Thyroid Fine NeedleAspiration Biopsy
      and Thinprep Cytology Test in Diagnosis ofThyroid Disease
AB  - Purpose: To study the clinical application value of ultrasound guided thyroid
      fine needle aspiration biopsy andthinprep cytology testing in diagnosis of
      thyroid disease. Methods: A total of 78 patients with thyroid nodules
      wereenrolled, 34 males and 44 females, aged 33-64 years old with mean age of 47.6
      years. All underwent thyroid modulefine needle puncture after surgery to assess
      cell pathology and histopathological features. Results: Sufficient specimenswere
      obtained from all of 78 patients, the cytological results of 73 cases (93.6 %)
      being consistent with pathologicalresults. While 20 cases (25.6 %) were malignant
      tumors, 44 (56.4 %) were benign and 9 (11.5 %) were non-tumor lesions.The
      sensitivity of benign and malignant thyroid nodule by thyroid fine needle
      puncture was 90.9 %, specificity was98.1 % and the positive predictive value was
      96.3 %. Conclusions: It is demonstrated that ultrasound-guided thyroidfine needle
      aspiration biopsy and thinprep cytology testing have diagnostic value in clinical
      application for thyroiddisease,showing good diagnostic coincidence rates with
      histopathological examination. They can thus be regarded assafe and effective for
      preoperative diagnosis and providing an appropriate basis for selection of
      surgery.

PMID- 27893199
TI  - Prognostic Factors in Stage III Non-Small-Cell Lung CancerPatients
AB  - Aim: The objective of this study is to investigate prognostic factors affecting
      survival of patients undergoingconcurrent or sequential chemoradiotherapy (CRT)
      for stage III non-small-cell lung cancer (NSCL). Methods andmaterials: We
      retrospectively reviewed the clinical records of 148 patients with advanced,
      inoperable stage IIINSCLC, who were treated between 2007 and 2015. Results: The
      median survival was found to be 19 months and3-year overall survival was 27%. Age
      (<65 vs >=65 years, p=0.026), stage (IIIA vs IIIB, p=0.033), dose of
      radiotherapy(RT) (<60 vs >=60 Gy, p=0.024) and treatment method (sequential
      chemotherapy+RT vs concurrent CRT , p=0.023)were found to be factors affecting
      survival in univariate analyses. Gender, histological subtype, weight loss
      duringCRT, performance status, induction/consolidation chemotherapy and presence
      of comorbidities did not affect survival(p>0.050). Conclusion: Young age, stage
      IIIA, radiotherapy dose and concurrent chemoradiotherapy may positivelyaffect
      survival in stage III NSCL cases.

PMID- 27893200
TI  - Clinical Impact of Overexpression of FOXP3 and WT1 onDisease Outcome in Egyptian
      Acute Myeloid Leukemia Patients
AB  - Background: In the last decade, it has become clear that change of gene
      expression may alter the hematopoietic cellquiescent state and consequently play
      a major role in leukemogenesis. WT1 is known to be a player in acute
      myeloidleukemia (AML) and FOXP3 has a crucial role in regulating the immune
      response. Objectives: To evaluate the impactof overexpression of WT1and FOXP3
      genes on clinical course in adult and pediatric AML patients in Egypt.
      Patientsand methods: Bone marrow and peripheral blood samples were obtained from
      97 de novo non M3 AML patients(63 adult and 34 pediatric). Real-time quantitative
      PCR was used to detect overexpression WT1 and FOXP3 genes.Patient follow up
      ranged from 0.2 to 39.0 months with a median of 5 months. Results: In the
      pediatric group; WT1was significantly expressed with a high total leukocyte count
      median 50X109/L (p=0.018). In the adult group, WT1had an adverse impact on
      complete remission induction, disease-free survival and overall survival (p=0.02,
      p=0.035,p=0.019 respectively). FOXP3 overexpression was associated with FAB
      subtypes AML M0 +M1 vs. M2, M4+M5 (p=0.039) and the presence of hepatomegaly
      (p=0.005). Conclusions: WT1 and FOXP3 overexpression has an adverseimpact on
      clinical presentation, treatment response and survival of pediatric and adult
      Egyptian AML patients.

PMID- 27893202
TI  - Role of GSTM1 Copy Number Variant in the Prognosis ofThai Colorectal Cancer
      Patients Treated with 5-FU-basedChemotherapy
AB  - Background: Glutathione S-transferase M1 (GSTM1) is involved in the
      detoxification of carcinogenic agents.DNA copy number variants of GSTM1 may be
      associated with cancer progression and may result in reduced survivaltime of
      various cancers. Determination of DNA copy number variants was here used to
      assess the associationbetween GSTM1 copy number variant and pathological status
      and survival time of colorectal-cancer patients treatedwith 5-fluorouracil-based
      chemotherapy. Methods: One hundred thirteen Thai colorectal-cancer patients
      wereinvestigated for GSTM1 copy number variant by real-time PCR. Relationships
      between gene copy number variantsand clinico-pathological parameters were
      determined. Result: Associations were evident between GSTM1 copynumber and stage
      of tumor (P = 0.026) and metastasis at diagnosis (P = 0.049), with odds ratio
      values of 0.2 and 0.3respectively. Conclusions: GSTM1 copy number variant was
      here not related with reduced overall survival for thecolorectal-cancer patients
      receiving 5-FU-based chemotherapy.

PMID- 27893201
TI  - Effects of Tobacco Smoking on the Dorsum of the Tongue andBuccal Epithelium
AB  - Objective: The aim of this study was to assess the effects of tobacco smoking on
      the dorsum of the tongue andbuccal epithelium. Methodology: This case control
      cross-sectional study was conducted with 174 smoking andnon-smoking volunteers
      living in the city of Hail, Northern KSA. Cytological Materials were obtained
      from buccalmucosa and dorsum of the tongue, and assessed using cytopathological
      methods. Results: In buccal smears, cytologicalatypia was observed in 17 out of
      101 (16.8%) smoker cases but only 3/73(4.1%) of the controls. For cytological
      atypiain buccal and tongue smears, the adjusted odd ratio (OR) and the 95%
      confidence interval (CI) were found to be 4.7(1.3-16.8), P < 0.016)) and 4.3
      (0.93- 20.2), P <0.06)), respectively, in the two sites. Conclusion: Tobacco
      smokingis a major risk factor for occurrence of cytological atypia, which might
      subsequently develop into oral precancerousand cancerous lesions. Oral
      exfoliative cytology is an easy and cheap non-invasive procedure which appears
      highlysuitable for screening populations at risk of developing oral cancer.

PMID- 27893203
TI  - High Mortality Rate of Stomach Cancer Caused Not by HighIncidence but Delays in
      Diagnosis in Aomori Prefecture, Japan
AB  - Background: There are substantial differences in the mortality rates of stomach
      cancer among the 47 prefecturesin Japan, and Aomori prefecture is one of the most
      severely impacted. The aims of this study were to determine theincidence and
      mortality rates of stomach cancer in Aomori prefecture in comparison with Japan
      as a whole and castlight on reasons underlying variation. Methods: Data on
      stomach cancer cases were extracted from the Aomori CancerRegistry Database.
      Incidence rates for specific stages at the time of diagnosis were cited from
      Monitoring of CancerIncidence in Japan, and mortality rates for stomach cancer in
      Aomori prefecture and the whole of Japan were obtainedfrom Vital Statistics. Age
      standardised incidence and mortality rates were calculated using the direct
      method. Results:The age-standardised incidence rate of stomach cancer in Aomori
      prefecture was higher than in the whole of Japan formales but lower for females.
      However, the age-standardised mortality rates were higher in Aomori prefecture in
      bothsexes. The proportion of localised cancers was lower in Aomori prefecture
      than in the whole of Japan for most agegroups. Conclusions: The lower rate for
      localised cancer suggests that higher age-standardised mortality rates are dueto
      delays in diagnosis, despite an attendance rate for stomach cancer screening was
      higher in Aomori prefecture thanin the whole of Japan. One plausible explanation
      for the failure of successful early detection might be poor qualitycontrol during
      screening implementation that impedes early detection.

PMID- 27893204
TI  - Estimating the Economic Burden of Lung Cancer in Iran
AB  - Objectives: Lung cancer is a major public health problem and one of the most
      costly illnesses. The study aimedto estimate the economic burden of lung cancer
      in Iran in 2014. Methods: A cross-sectional study was conducted toestimate the
      direct and indirect costs for patients with lung cancer using a prevalence-based
      approach. A human capitalapproach was employed to estimate the indirect costs.
      Data were obtained from several sources such as through patientinterview using
      structured questionnaire, medical records, the GLOBOCAN databases, the Iranian
      Statistical Center,the Iranian Ministry of Cooperation, Labor and Social Welfare,
      and the Institute for Health Metrics and Evaluation(IHME). Results: The economic
      burden of lung cancer in Iran in the year 2014 was 3,225,998,555,090 IR. The
      maincomponents of the cost were associated with mortality (81.9 %) and
      hospitalization (7.6 %). The costs of direct medicalcare, non-medical aspects,
      patient time, and mortality accounted for 10.8%, 2.7%, 4.5%, and 81.5% of the
      total cost,respectively. Conclusion: Findings from this study indicated that the
      economic burden of lung cancer is substantialboth to Iran's health system and to
      society as a whole. Early diagnosis, strengthening cancer prevention,
      implementingnew cancer therapy and medical technology, and effective smoking
      cessation interventions could offset some of thecosts associated with lung cancer
      in Iran.

PMID- 27893205
TI  - Patterns of Recurrence after Resection of Mass-Forming TypeIntrahepatic
      Cholangiocarcinomas
AB  - Background: Intrahepatic cholangiocarcinoma (IHCCA) is an aggressive tumor for
      which surgical resection isa mainstay of treatment. However, recurrence after
      resection is common associated with a poor prognosis. Studiesregarding recurrence
      of mass-forming IHCCA are rare; therefore, we investigated the pattern with our
      dataset. Methods:We retrospectively reviewed the medical and pathological records
      of 50 mass-forming IHCCA patients who underwenthepatic resection between January
      2004 and December 2009 in order to determine the patterns of recurrence
      andprognosis. All demographic and operative parameters were analyzed for their
      effects on recurrence-free survival.Results: The median recurrence-free survival
      time was 188 days (95%CI: 149-299). The respective 1-, 2-, and 3-yearrecurrence
      free survival rates were 16.2% (95%CI: 6.6-29.4), 5.4% (95%CI: 1.0-15.8) and 2.7%
      (95%CI: 0.2-12.0).There was an equal distribution of recurrence at solitary and
      multiple sites. Univariate analysis revealed no factorsrelated to recurrence-free
      survival.Conclusion: The overall survival and recurrence-free survival after
      surgery formass-forming IHCCA were found to be very poor. Almost all recurrences
      were detected within 2 years after surgery.Adjuvant chemotherapy after surgery
      may add benefit in the affected patients.

PMID- 27893206
TI  - No Significant Association between Human Papillomavirusand Breast Cancer,
      Sanandaj, Iran
AB  - Background and Objective: Any role of human papillomavirus (HPV) in the
      development of breast cancer isconjectural. The aim of this study was to
      investigate possible links between HPV and breast cancer in women, Sanandaj,Iran.
      Methods: In this case-control study, 70 formalin fixed and paraffin embedded
      blocks of breast malignant tumorsas a case group and 70 blocks of lesions without
      malignancy were selected as controls. Sections about 10 MUm thickwere prepared.
      After removing the paraffin, DNA was extracted. Samples were tested by PCR using
      general and highriskspecific HPV primers. Results: All 70 malignant breast tumors
      (cases) were invasive ductal carcinomas, and ofthe 70 controls, 17 (24.3%) were
      fibrocystic tumors and 53 (75.7%) fibroadenomas. The age range of women in
      thecase group was 25-72 years old and in the control group It was13-66 years.
      Using HPV general primers two sampleswere positive in the case group, confirmed
      to be HPV-18 using high-risk specific primers. Conclusion: No
      statisticallysignificant association was found between breast cancer and HPV. It
      is necessary to confirm this result by furtherinvestigations in other
      populations.

PMID- 27893207
TI  - Prevalence and Risk Factors for Helicobacter Pylori Infection among Healthy
      Inhabitants in Northern Jakarta, Indonesia
AB  - Background: The prevalence of Helicobacter pylori (H. pylori) infection in
      Indonesia has been reported to beexceedingly low. The purpose of our study was to
      confirm whether this is the case in Northern Jakarta using a sensitive13C-urea
      breath test (UBT), and to examine any associations with lifestyle/environment
      factors and potential routesof transmission. Methods: We recruited a total of 196
      subjects from a low-income community in Northern Jakarta,Indonesia, data from 193
      who completed a questionnaire about their lifestyle/environment and had UBT being
      includedas the final. Odds ratios (ORs) adjusted for sex and age with 95%
      confidence intervals (CIs) were calculated using alogistic regression model.
      Results: The overall H. pylori infection rate was 15.0% (95%CI, 10.3-20.9), with
      variationamong Javanese (9.1%, total=77), Buginese (40.0%, 35), Betawi (9.1%,
      33), Sundanese (3.7%, 27), and Batak (40.0%,5). On multivariate analysis, the ORs
      for intake of soybean milk, cucumber more than once a week, infrequent
      handwashing practice before meals, and alcohol consumption were 0.10 (95%CI: 0.01
      0.97), 6.61 (95%CI: 1.87-23.3), 4.10(95%CI: 1.15-14.6), and 61.9 (95%CI: 1.67
      2300.8), respectively. Rates for Buginese (OR=7.84; 95%CI: 1.82-33.8)and Batak
      (OR=20.1; 95%CI: 1.90-213.2) were significantly higher than for Javanese.
      Conclusions: The H. pyloriinfection rate in this study was relatively low, in
      line with previous studies. Regarding ethnicity factors, Buginese andBatak
      reported eating food using fingers more frequently than Javanese, Betawi, and
      Sundanese. Our study indicatedthat person-person transmission is possible in this
      low prevalence area. The low infection rates for H. pylori amongJavanese, Betawi,
      and Sundanese ethnics could be partly due to their sanitary practices.

PMID- 27893208
TI  - Kanahia Laniflora Methanolic Extract Suppressed Proliferation of Human Non-Small
      Cell Lung Cancer A549 Cells
AB  - Introduction: Lung cancer is one of the most common cancers worldwide. In certain
      countries such as UnitedStates of America, it is the leading cause of related
      cancer mortality among both men and women. Natural productsplay an important role
      in overcoming the limitations of chemotherapy and radiotherapy. Objectives: In
      this study,we investigated the antiproliferative and apoptotic activities of
      Kanahia laniflora methanolic extract against humannon-small cell lung cancer
      cells (A549). Methods: Sulforhodamine B colorimetric assays were used to
      determinethe inhibitory effects of a leaf methanolic extract against A549 cells.
      Results: The extract showed strong cytotoxicactivity against A549 cells with an
      IC50 value of 0.13 MUg/ml compared to 0.21 MUg/ml for doxorubicin. The extract
      alsosignificantly increased the percentage of apoptotic cells to 49.7% as
      compared to 1.4% and 47.4% for control anddoxorubicin respectively. Conclusion:
      These results showed, for the first time, that a methanolic extract of
      Kanahialaniflora leaves can inhibit the proliferation of human non-small cell
      lung cancer cells (A549). Further attention to itspotential as a new effective
      anticancer agent is warranted.

PMID- 27893209
TI  - Determination of Metal Levels in Shamma (Smokeless Tobacco) with Inductively
      Coupled Plasma Mass Spectrometry (ICP-MS) in Najran, Saudi Arabia
AB  - Objective: The use of Shamma (smokeless tobacco) by certain groups is giving rise
      to health problems, includingcancer, in parts of Saudi Arabia. Our objective was
      to determine metals levels in Shamma using inductively coupledplasma mass
      spectrometry (ICP-MS). Methods: Thirty-three samples of Shamma (smokeless
      tobacco) were collected,comprising four types: brown Shamma (n = 14.0), red
      Shamma (n = 9.0), white Shamma (n = 4.0), and yellow Shamma(n = 6.0). All samples
      were collected randomly from Shamma users in the city of Najran. Levels of 11
      elements (Al,As, Cd, Co, Cr, Cu, Li, Mn, Ni, Pb, and Zn) were determined by ICP
      MS. Results: A mixed standard (20 ppb) of allelements was used for quality
      control, and average recoveries ranged from 74.7% to 112.2%. The highest
      averageconcentrations were found in the following order: Al (598.8-812.2 MUg/g),
      Mn (51.0-80.6 MUg/g), and Ni (23.2-53.3 MUg/g)in all four Shamma types. The
      lowest concentrations were for As (0.7-1.0 MUg/g) and Cd (0.0-0.06 MUg/g).
      Conclusions:The colour of each Shamma type reflects additives mixed into the
      tobacco. Cr and Cu were showed significant differences(P < 0.05) among Shamma
      types. Moreover, Pb levels are higher in red and yellow Shamma, which could be
      due touse (PbCrO4) as yellow colouring agent and lead tetroxide, Pb3O4 as a red
      colouring agent. The findings from thisstudy can be used to raise public
      awareness about the safety and health effects of Shamma, which is clearly a
      sourceof oral exposure to metals.

PMID- 27893210
TI  - Impact of Treatment Type on Overall Survival in ElderlyBrazilian Women with
      Breast Cancer
AB  - Objective: To analyze the survival of elderly patients with breast cancer
      according to the type of treatment used.Methods: A cohort study of women aged 80
      or over with breast cancer registered with the Brazilian National CancerInstitute
      (Instituto Nacional do Cancer - INCA) between 2008 and 2009 was conducted.
      Prognosis was analyzedaccording to the cancer treatment performed: surgery,
      radiotherapy, or hormone therapy. Analysis of the overall 5-yearsurvival rate was
      performed using the Kaplan - Meier method, and comparisons of curves were
      undertaken using thelog-rank test. For multiple regression analysis, Cox
      regression was used, adjusting for age and clinical stage, consideringvalues of p
      < 0.05 as significant. Data were all analyzed using the statistical package SPSS
      version 20. Results: 70women with a mean age of 84.0 +/- 3.7 years at diagnosis
      participated in the study. The median follow-up time was37.1 months (range 0.5
      75.5), and 31 deaths (44.3%) occurred during this time. The median survival time
      was 51.2months (95% CI, 44.9-57.4), higher in those who underwent surgery (p =
      0.012) and those who had hormone therapy(p=0.001). Treatment with surgery reduced
      the risk of death by 61.7% (HR 0.3; 95% CI, 0.1-0.6; p = 0.001) whenadjusted for
      clinical stage and age at diagnosis. However, there was no significant benefit
      from radiotherapy (HR 1.2;95% CI, 0.5-2.5; p = 0.694). Conclusion: Treatment with
      surgery and hormone therapy increased the survival of ourBrazilian patients with
      breast cancer aged 80 or over.

PMID- 27893211
TI  - Changes in the Distribution of Cancer Incidence in Nepal from 2003 to 2013
AB  - Background: Cancer incidence data are vital for cancer control planning in any
      nation. This retrospective studywas conducted to compare the cancer incidence of
      all sites between the first cancer registry report and the most recentexample in
      Nepal. Material and Methods: The cases in the first (2003) and latest (2013)
      national cancer registryreports, accumulated by all the hospital based cancer
      registries in Nepal were taken for the research. The frequencies,crude incidences
      and age specific incidences (per 100,000) of the five major cancers were
      calculated for both malesand females. Result: The most common cancer type for
      males in both years 2003 and 2013 was lung. Stomach wasthe third most common
      cancer in 2003 while it was the second in 2013. Similarly, the first four major
      cancers (cervix,breast, lung and ovary) did not change between 2003 and 2013 in
      females. The total cancer incidence rate increased from12.8 in 2003 to 30.4 per
      100,000 in 2013 for males and from 15.1 to 33.3 in females. Conclusion: The most
      commoncancers in males in 2003 and 2013 were in the bronchus and lung. Similarly,
      the most common cancer in females wascervix at both time points. The cancer
      incidence rate in females was higher than in males both in 2003 and 2013.

PMID- 27893213
TI  - Reliability and validity of data obtained from alcohol, cannabis, and gambling
      populations on Amazon's Mechanical Turk.
AB  - Researchers recently have begun using Mechanical Turk (MTurk), an online
      crowdsourcing platform, to recruit addiction populations. However, whether the
      data obtained from substance users and gamblers on MTurk are reliable and valid
      is unknown. Herein, we assessed the internal and retest reliability of and
      concurrent and convergent validity of data obtained from addiction populations on
      MTurk. Current drinkers (N = 208), cannabis users (N = 200), and gamblers (N =
      200) residing in the United States completed measures of alcohol, cannabis, and
      gambling severity, psychological constructs (e.g., impulsivity) related to
      addictions, overt and subtle measures of valid responding, and motivations for
      completing MTurk studies. Of the original sample, 88-92% of participants who
      provided informed consent for recontact completed a reassessment 1 week later.
      The internal consistency of the addiction severity measures ranged from alpha =
      .75 to .93. The stability over 1 week ranged from kappa = .57 to .70 for
      categorical classification, and intraclass correlation coefficient (ICC) = .71 to
      .86 for continuous measures. The addiction measures were significantly correlated
      with each other and with other constructs related to addictive behaviors.
      Overall, 80-85% of participants provided valid responses. They reported attending
      and answering questions honestly, with financial motives being the most
      frequently endorsed motivation. After invalid responses were excluded, results
      remained the same for alcohol and gambling, but significant differences emerged
      for the cannabis sample. The results suggest that the self-report data obtained
      from alcohol and gambling populations are of high quality, however, caution is
      warranted with cannabis populations. MTurk shows promise as a recruitment tool
      for some addictive behaviors. (PsycINFO Database Record

PMID- 27893212
TI  - Effects of Energy Conservation Strategies on Cancer Related Fatigue and Health
      Promotion Lifestyle in Breast CancerSurvivors: a Randomized Control Trial
AB  - Purpose: Cancer-related fatigue is frequently experienced by patients during and
      after therapy. The present studywas conducted to assess the impact of energy
      conservation strategies and health promotion in breast cancer survivors.Methods:
      A randomized controlled trial was carried out to compare the intervention effect
      (n=69.0) with controls(n=66.0) based on routine oncology ward care. The
      intervention was five weekly sessions for groups of 6-8 breast cancersurvivors.
      Data on fatigue and health promotion lifestyle were obtained before and after
      completion the interventionand then 8 weeks later for analysis of variance
      (ANOVA) with repeated measures. Results: Our findings showedcancer-related
      fatigue to be reduced in the intervention group from pre- to post-intervention,
      and this persisted overthe 8-weeks follow-up period (F = 69.8, p<0.001). All
      subscales of the cancer fatigue scale demonstrated statisticallysignificant
      effects with partial eta-squared values ranging from 0.15 (the smallest effect in
      cognitive fatigue) to 0.21(the largest for affective fatigue). Changes in the
      health promotion life style indicated a significant promotion frompre- to post
      intervention, and this again continued after 8-weeks follow-up (F = 41.6, p <
      0.001). All six domains ofa health promoting life style featured significantly
      elevated values, the largest effect being seen in the interpersonalrelations
      subscale (F=57.7, partial eta2=0.21, p<0.001) followed by physical activity
      (F=51.9, partial eta2=0.18, p<0.001).Conclusions: The program was effective in
      decreasing cancer related fatigue and promoting a healthy lifestyle.

PMID- 27893214
TI  - Public perceptions of behavioral and substance addictions.
AB  - Most of the research on public perceptions of people with addictive disorders has
      focused on alcohol and illicit drugs, rather than addiction to behavioral
      activities. To expand the range of addictive behaviors and types of perceptions
      studied, we designed the present study to assess the lay public's definitions of
      and willingness to affiliate with people described as addicted to 1 of 2 specific
      behaviors (i.e., pornography or gambling) or 1 of 3 specific substances (i.e.,
      alcohol, marijuana, or heroin). A nationwide convenience sample (N = 612) of
      American adults completed online questionnaires during the summer of 2015.
      Participants rated heroin as more addictive than the other drugs and behaviors
      and, despite differences among the conditions, were generally unwilling to
      affiliate with an individual addicted to any of the 2 behaviors or 3 substances.
      When asked to rate different potential indications of addiction, participants
      endorsed behavioral signs of impaired control and physiological and psychological
      dependence as more indicative of all 5 types of addiction than desire to use the
      substance or engage in the addictive behavior. Despite recent efforts to increase
      public knowledge about addictive disorders, members of the public continue to
      endorse some attitudes indicative of stigmatization toward people with selected
      substance and behavioral addictions. (PsycINFO Database Record

PMID- 27893215
TI  - Type I error rates and power of several versions of scaled chi-square difference
      tests in investigations of measurement invariance.
AB  - A Monte Carlo simulation study was conducted to investigate Type I error rates
      and power of several corrections for nonnormality to the normal theory chi-square
      difference test in the context of evaluating measurement invariance via
      structural equation modeling. Studied statistics include the uncorrected
      difference test, DML, Satorra and Bentler's (2001) original correction, DSB1,
      Satorra and Bentler's (2010) strictly positive correction, DSB10, and a hybrid
      procedure, DSBH (Asparouhov & Muthen, 2013). Multiple-group data were generated
      from confirmatory factor analytic population models invariant on all parameters,
      or lacking invariance on residual variances, indicator intercepts, or factor
      loadings. Conditions varied in terms of the number of indicators associated with
      each factor in the population model, the location of noninvariance (if any),
      sample size, sample size ratio in the 2 groups, and nature of nonnormality. Type
      I error rates and power of corrected statistics were evaluated for a series of 4
      nested invariance models. Overall, the strictly positive correction, DSB10, is
      the best and most consistently performing statistic, as it was found to be much
      less sensitive than the original correction, DSB1, to model size and sample
      evenness. (PsycINFO Database Record

PMID- 27893216
TI  - Assessing the fit of structural equation models with multiply imputed data.
AB  - Multiple imputation has enjoyed widespread use in social science applications,
      yet the application of imputation-based inference to structural equation modeling
      has received virtually no attention in the literature. Thus, this study has 2
      overarching goals: evaluate the application of Meng and Rubin's (1992) pooling
      procedure for likelihood ratio statistic to the SEM test of model fit, and
      explore the possibility of using this test statistic to define imputation-based
      versions of common fit indices such as the TLI, CFI, and RMSEA. Computer
      simulation results suggested that, when applied to a correctly specified model,
      the pooled likelihood ratio statistic performed well as a global test of model
      fit and was closely calibrated to the corresponding full information maximum
      likelihood (FIML) test statistic. However, when applied to misspecified models
      with high rates of missingness (30%-40%), the imputation-based test statistic
      generally exhibited lower power than that of FIML. Using the pooled test
      statistic to construct imputation-based versions of the TLI, CFI, and RMSEA
      worked well and produced indices that were well-calibrated with those of full
      information maximum likelihood estimation. This article gives Mplus and R code to
      implement the pooled test statistic, and it offers a number of recommendations
      for future research. (PsycINFO Database Record

PMID- 27893217
TI  - Multi-relational measurement for latent construct networks.
AB  - Multiple item scales have long been used to measure latent constructs on
      individual-level data. This is appropriate when an otherwise unobserved construct
      is indirectly measured by combining observable correlated characteristics that
      are thought to measure slightly different dimensions of that construct. Network
      data, which consist of observations on the relationships between a set of actors,
      however, are typically drawn from single-relation measurements. While this
      approach is sufficient for learning about discrete relations (communication,
      coauthorship, etc.), multi-item measurement of extemporaneous valued
      relationships, such as cohesion and conflict, may be of common interest in
      psychology and related sciences. In this article, we evaluate the use of
      multirelational network measurement in inferring valued latent construct
      networks. In particular, we present a psychometric framework for developing
      multirelational measures of latent construct networks, evaluating their
      reliability and construct validity, and identification of appropriate scaling
      approaches for these construct-level networks. (PsycINFO Database Record

PMID- 27893218
TI  - Measuring response styles in Likert items.
AB  - The recently proposed class of item response tree models provides a flexible
      framework for modeling multiple response processes. This feature is particularly
      attractive for understanding how response styles may affect answers to
      attitudinal questions. Facilitating the disassociation of response styles and
      attitudinal traits, item response tree models can provide powerful process tests
      of how different response formats may affect the measurement of substantive
      traits. In an empirical study, 3 response formats were used to measure the 2
      dimensional Personal Need for Structure traits. Different item response tree
      models are proposed to capture the response styles for each of the response
      formats. These models show that the response formats give rise to similar trait
      measures but different response-style effects. (PsycINFO Database Record

PMID- 27893219
TI  - Integrating the context-appropriate balanced attention model and reinforcement
      sensitivity theory: Towards a domain-general personality process model.
AB  - Over the last 40 years or more the personality literature has been dominated by
      trait models based on the Big Five (B5). Trait-based models describe personality
      at the between-person level but cannot explain the within-person mental
      mechanisms responsible for personality. Nor can they adequately account for
      variations in emotion and behavior experienced by individuals across different
      situations and over time. An alternative, yet understated, approach to
      personality architecture can be found in neurobiological theories of personality,
      most notably reinforcement sensitivity theory (RST). In contrast to static trait
      based personality models like the B5, RST provides a more plausible basis for a
      personality process model, namely, one that explains how emotions and behavior
      arise from the dynamic interaction between contextual factors and within-person
      mental mechanisms. In this article, the authors review the evolution of a
      neurobiologically based personality process model based on RST, the response
      modulation model and the context-appropriate balanced attention model. They argue
      that by integrating this complex literature, and by incorporating evidence from
      personality neuroscience, one can meaningfully explain personality at both the
      within- and between-person levels. This approach achieves a domain-general
      architecture based on RST and self-regulation that can be used to align within
      person mental mechanisms, neurobiological systems and between-person measurement
      models. (PsycINFO Database Record

PMID- 27893220
TI  - Is body dissatisfaction changing across time? A cross-temporal meta-analysis.
AB  - It remains unclear whether body dissatisfaction, a widely recognized predictor of
      eating-related pathologies and depressive symptomatology, is consistent across
      cohorts and time. This question is important to investigate because dominant
      theories propose that sociocultural influences, which may fluctuate, play an
      important role in the development of body dissatisfaction. Previous efforts for
      tracking body dissatisfaction across cohorts and time are limited by relying on
      data from a single institution or using assessments that lack psychometric
      support across genders. In this study, we utilized cross-temporal meta-analyses
      to examine changes in 2 dimensions of body dissatisfaction: thinness-oriented
      dissatisfaction as assessed with the Eating Disorder Inventory-Body
      Dissatisfaction subscale (data available across 31 years from 326 unique samples,
      n = 100,228 participants) and muscularity-oriented dissatisfaction as measured
      with the Drive for Muscularity Scale (data available across 14 years from 117
      unique samples, n = 23,575 participants). Results revealed a significant
      interaction between year of study and gender in predicting thinness-oriented
      dissatisfaction: girls and women scored higher than boys and men consistently (ds
      = 0.51-1.17), although only girls' and women's scores decreased gradually across
      time (d = 0.49). Boys and men scored higher than girls and women on muscularity
      oriented dissatisfaction (d = 1.72), with no significant changes across time.
      These patterns remained when controlling for age and geographic location.
      Overall, these findings highlight the importance of considering multiple
      dimensions of body dissatisfaction in research and offer evidence that
      sociocultural shifts in body acceptance and diversity may be countering thinness
      related pressures for girls and women. (PsycINFO Database Record

PMID- 27893221
TI  - Substance use and psychological distress is related with accommodation status
      among homeless immigrants.
AB  - Immigrant homelessness constitutes a cruel expression of social exclusion. We
      analyzed the relation of sociodemographic characteristics with stressful life
      events, substance use and psychological distress, giving a special importance to
      the influence of the time spent on the streets and the accommodation status of
      107 homeless immigrants. To this end, both quantitative and qualitative
      methodologies were combined. Discussion groups with care resources practitioners
      and service users, were followed by in depth interviews combined with
      psychometric questionnaires. Results show clear interrelations between stressful
      life events, alcohol and drug use, psychological distress, and the duration of
      (current) homelessness. This information, and especially the contextualization
      which took place within the analytical framework of this project, may provide
      practitioners and policymakers with information that can help overcome barriers
      preventing homeless immigrants' full citizenship and social participation.
      (PsycINFO Database Record

PMID- 27893222
TI  - The emotion seen in a face can be a methodological artifact: The process of
      elimination hypothesis.
AB  - The claim that certain facial expressions signal certain specific emotions has
      been supported by high observer agreement in labeling the emotion predicted for
      that expression. Our hypothesis was that, with a method common to the field, high
      observer agreement can be achieved through a process of elimination: As
      participants move from trial to trial and they encounter a type of expression not
      previously encountered in the experiment, they tend to eliminate labels they have
      already associated with expressions seen on previous trials; they then select
      among labels not previously used. Seven experiments (total N = 1,068) here showed
      that the amount of agreement can be altered through a process of elimination. One
      facial expression not previously theorized to signal any emotion was consensually
      labeled as disgusted (76%), annoyed (85%), playful (89%), and mischievous (96%).
      Three quite different facial expressions were labeled nonplussed (82%, 93%, and
      82%). A prototypical sad expression was labeled disgusted (55%), and a
      prototypical fear expression was labeled surprised (55%). A facial expression was
      labeled with a made-up word (tolen; 53%). Similar results were obtained both in a
      context focused on demonstrating a process of elimination and in one similar to a
      commonly used method, with 4 target expressions embedded with other expressions
      in 24 randomly ordered trials. (PsycINFO Database Record

PMID- 27893224
TI  - The influence of a word's number of letters, spatial extent, and initial bigram
      characteristics on eye movement control during reading: Evidence from Arabic.
AB  - The authors conducted 2 eye movement experiments in which they used the
      typographical and linguistic properties of Arabic to disentangle the influences
      of words' number of letters and spatial extent on measures of fixation duration
      and saccade targeting (Experiment 1), and to investigate the influence of initial
      bigram characteristics on saccade targeting during reading (Experiment 2). In the
      first experiment, through the use of a proportional font, which is more natural
      looking in Arabic compared to monospaced fonts, the authors manipulated the
      number of letters (5 vs. 7) and the spatial extent (wide vs. narrow) of words
      embedded in frame sentences. The results obtained replicate and expand upon
      previous findings in other alphabetic languages that the number of letters
      influences fixation durations, whereas saccade targeting (as indicated by
      measures of fixation count and probability of skipping and refixation) is more
      influenced by the word's spatial extent. In the second experiment, the authors
      compared saccade targeting measures (saccade amplitude and initial fixation
      location) in 6- and 7-letter words beginning with initial bigrams that were of
      extremely high frequency (|? the), relatively high frequency (?? to/for the), or
      beginning with the letters of the word stem. The results showed negligible
      modulation of saccade targeting by initial bigram characteristics. The results
      also highlighted the importance of selecting the appropriate measures of initial
      fixation location (spatial vs. character-based measures) during reading text
      rendered using proportional fonts. (PsycINFO Database Record

PMID- 27893225
TI  - "Profiling pathological narcissism according to DSM-5 domains and traits: A study
      on consecutively admitted Italian psychotherapy Patients": Correction to Fossati
      et al. (2016).
AB  - Reports an error in "Profiling pathological narcissism according to DSM-5 domains
      and traits: A study on consecutively admitted Italian psychotherapy patients" by
      Andrea Fossati, Antonella Somma, Serena Borroni, Aaron L. Pincus, Kristian E.
      Markon and Robert F. Krueger (Psychological Assessment, Advanced Online
      Publication, Jun 23, 2016, np). In the article, several values were reversed and
      the mean was misreported in Table 2. The corrected table is present in the
      erratum. (The following abstract of the original article appeared in record 2016
      31181-001.) Pathological narcissism represents a clinically relevant, albeit
      controversial personality construct, with multiple conceptualizations that are
      operationalized by different measures. Even in the recently published Diagnostic
      and Statistical Manual for Mental Disorders-Fifth Edition (DSM-5), 2 different
      views of narcissistic personality disorder (NPD) are formulated (i.e., Section II
      and Section III). The DSM-5 Section III alternative PD model diagnosis of NPD is
      based on self and interpersonal dysfunction (Criterion A) and a profile of
      maladaptive personality traits (Criterion B), specifically elevated scores on
      Attention Seeking and Grandiosity. Given the diversity of conceptualizations of
      pathological narcissism, we evaluated the convergences and divergences in DSM-5
      trait profiles characterizing multiple measures of narcissism in a clinical
      sample of 278 consecutively admitted Italian psychotherapy patients. Patients
      were administered the Italian versions of the Personality Inventory for DSM-5
      (PID-5) and 4 measures of NPD, (a) the Narcissistic Personality Inventory (NPI);
      (b) the NPD scale of the Personality Diagnostic Questionnaire-4+; (c) the
      Structured Clinical Interview for Axis II Personality Disorders, Version 2.0
      (SCID-II) as an observer-rated measure of NPD; and (d) the Pathological
      Narcissism Inventory (PNI). Multiple regression analyses showed that PID-5 traits
      explained from 13% to more than 60% of the variance in the different NPD
      measures. Attention Seeking was consistently associated with all measures of NPD,
      whereas Grandiosity was associated with some of the NPD measures. All measures of
      NPD were also significantly related to additional DSM-5 maladaptive traits.
      (PsycINFO Database Record

PMID- 27893223
TI  - Intervention with the mother-infant relationship reduces cell proliferation in
      the Locus Coeruleus of female rat pups.
AB  - The Locus Coeruleus (LC) is a noradrenergic nucleus involved in several
      neuroendocrine and behavioral functions. During the neonatal period, the LC is
      critical for olfactory learning. Full development occurs during the early
      postnatal period. Environmental interventions after birth may affect
      neurogenesis. In rats, the neonatal handling procedure has been used as a model
      to analyze the effects of environmental intervention early in life. It has been
      related to several long-lasting behavioral and neuroendocrine changes. The
      present study analyzed the effects of handling on the number of neurons, cellular
      proliferation, and apoptosis in the LC of 11-day-old female rats. Wistar rat pups
      were submitted to brief maternal separation followed by handling (1 min per day
      from postnatal day [PND] 1 to 10). On PND 11, the LC was analyzed using
      immunohistochemistry for NeuN and BrdU, TUNEL staining, and electron microscopy.
      The intervention reduced the number of neurons in the LC but showed no
      significant change in the number of apoptotic cells, as measured by the TUNEL
      technique. However, the number of proliferating cells was significantly lower in
      the handled rat pups as compared with the nonhandled ones. This study
      demonstrates that the infant LC is sensitive to changes in maternal behavior. A
      seemingly mild environmental intervention during the neonatal period may
      reprogram the development of the LC, altering cell proliferation. (PsycINFO
      Database Record

PMID- 27893226
TI  - The relation between the bifactor model of the Youth Psychopathic Traits
      Inventory and conduct problems in adolescence: Variations across gender, ethnic
      background, and age.
AB  - The current study examines how the bifactor model of the Youth Psychopathic
      Traits Inventory (YPI) is related to conduct problems in a sample of Dutch
      adolescents (N = 2,874; 43% female). It addresses to what extent the YPI
      dimensions explain variance over and above a General Psychopathy factor (i.e.,
      one factor related to all items) and how the general factor and dimensional
      factors are related to conduct problems. Group differences in these relations for
      gender, ethnic background, and age were examined. Results showed that the general
      factor is most important, but dimensions explain variance over and above the
      general factor. The general factor, and Affective and Lifestyle dimensions, of
      the YPI were positively related to conduct problems, whereas the Interpersonal
      dimension was not, after taking the general factor into account. However, across
      gender, ethnic background, and age, different dimensions were related to conduct
      problems over and above the general factor. This suggests that all 3 dimensions
      should be assessed when examining the psychopathy construct. (PsycINFO Database
      Record

PMID- 27893228
TI  - Ethnic identity: Factor structure and measurement invariance across ethnic
      groups.
AB  - Considering a historically diversified (and growing) population in the United
      States, one's ethnic identification is often an important psychological-as well
      as social and political-construct because it can serve as a hindrance to
      interpersonal interaction. Despite the importance of ethnic identity in
      psychological research, the most widely developed ethnic identity measurement
      tool, the Multigroup Ethnic Identity Measure (MEIM; Phinney, 1992), lacks
      consensus regarding its psychometric properties. The purpose of this article is
      to identify the factor structure of this measure and identify whether it exhibits
      measurement equivalence/invariance (ME/I) across ethnicities. The current
      findings offer several contributions to the state of the literature. First, our
      data suggests a two-factor model, including affirmation/commitment and
      exploration factors, is the most appropriate structure when considering fit and
      parsimony indices via confirmatory factor analysis. Second, configural and metric
      measurement equivalence was found across Caucasian and non-Caucasian
      participants. Interestingly, partial scalar invariance was established when
      comparing Caucasians with the minority groups with the exception of the Hispanic
      subgroup, which exhibited no scalar invariance. Third, differences in ethnic
      identity factor means were found, especially across Caucasians and African
      Americans. In conclusion, the use of the two-factor model of the MEIM is
      recommended, and results suggest that the MEIM is an appropriate measure of
      ethnic identity in most ethnic groups. Limitations and future research are also
      discussed. (PsycINFO Database Record

PMID- 27893227
TI  - A measure of perceived family stigma: Validity in a military sample.
AB  - The primary aim of the present study was to evaluate the reliability and validity
      of the newly developed Perceived Family Stigma Scale (PFSS) in a diverse sample
      of 623 military veterans. The PFSS is a 4-item scale that has acceptable internal
      consistency (alpha = .86) and strong interitem correlations (r = .51 to .76).
      Confirmatory factor analysis (CFA) indicated the single factor model was a good
      fit statistically (chi2[df = 2, N = 620] = .34, p = .84) and descriptively (CFI =
      1.00, RMSEA < .001). Multigroup CFA was performed to test the measurement
      invariance of the PFSS across demographic indicators. The PFSS achieved full
      scalar invariance across deployment history, education level, urban/rural
      location, marital status, and military rank, and partial scalar invariance across
      gender, ethnicity/race, and income level. Results of a logistic regression
      analysis indicated significant relationships of mean PFSS scores and gender with
      likelihood of needing help for an emotional problem, above and beyond a measure
      of self- and public stigma. Specifically, each point increase in mean PFSS scores
      predicted an almost 4 times higher probability of reporting a need for help, and
      men were also 6 times more likely than women to report a need for help. However,
      there was a significant relationship between the PFSS and gender such that, for
      women, each 1 point increase in mean PFSS scores predicted a likelihood of
      reporting a need/desire for help for an emotional problem 3 times that of men.
      (PsycINFO Database Record

PMID- 27893229
TI  - Measurement invariance of the Yale Food Addiction Scale 2.0 across gender and
      racial groups.
AB  - Food addiction describes a psychological and behavioral eating pattern that is
      similar to the experience of those compulsively taking drugs of abuse. Recent
      developments related to food addiction, including the development and validation
      of an updated measure (Yale Food Addiction Scale 2.0; Gearhardt, Corbin, &
      Brownell, 2016), have increased knowledge as to the prevalence and associated
      correlates of food addiction. However, less is known about the phenomenological
      experience of food addiction in diverse samples or how the existing measure of
      food addiction performs in heterogeneous samples. In a cross-sectional survey
      design, using a diverse sample of undergraduate students (N = 642) tests of
      measurement invariance were performed. Confirmatory factor analysis supported the
      hypothesized factor structure, indicating a single latent construct of food
      addiction modeled by 11 dichotomous indicators, in samples of White and Black
      participants as well as samples of men and women. Measurement invariance testing
      across the various demographic groups broadly provided good psychometric support
      for use of the measure. However, a single indicator related to attempts to cut
      down on highly palatable food varied across men and women. Thus, when using the
      measure in mixed gender samples researchers may consider obtaining additional
      information regarding gender and its relative impact on the experience of food
      addiction, particularly with respect to efforts to quit or cut down intake of
      highly palatable foods. (PsycINFO Database Record

PMID- 27893232
TI  - Narrative production in children with autism spectrum disorder (ASD) and children
      with attention-deficit/hyperactivity disorder (ADHD): Similarities and
      differences.
AB  - The present study focuses on the similarities and differences in language
      production between children with autism spectrum disorder (ASD) and children with
      attention-deficit/hyperactivity disorder (ADHD). In addition, we investigated
      whether Theory of Mind (ToM), working memory, and response inhibition are
      associated with language production. Narratives, produced by 106 Dutch-speaking
      children (36 with ASD, 34 with ADHD, and 36 typically developing) aged 6 to 12
      during ADOS assessment, were examined on several linguistic measures: verbal
      productivity, speech fluency, syntactic complexity, lexical semantics, and
      discourse pragmatics. Children were tested on ToM, working memory, and response
      inhibition and parents filled in the Children's Communication Checklist (CCC-2).
      Gold-standard diagnostic measures (Autism Diagnostic Observation Schema [ADOS],
      Autism Diagnostic Interview Revised [ADI-R], and the Parent Interview for Child
      Symptoms [PICS]) were administered to all children to confirm diagnosis.
      Regarding similarities, both clinical groups showed impairments in narrative
      performance relative to typically developing children. These were confirmed by
      the CCC-2. These impairments were not only present on pragmatic measures, such as
      the inability to produce a narrative in a coherent and cohesive way, but also on
      syntactic complexity and their production of repetitions. As for differences,
      children with ADHD but not children with ASD showed problems in their choice of
      referring expressions and speech fluency. ToM and working memory performance but
      not response inhibition were associated with many narrative skills, suggesting
      that these cognitive mechanisms explain some of the impairments in language
      production. We conclude that children with ASD and children with ADHD manifest
      multiple and diverse language production problems, which may partly relate to
      their problems in ToM and working memory. (PsycINFO Database Record

PMID- 27893230
TI  - Ecological momentary assessment of negative symptoms in schizophrenia:
      Relationships to effort-based decision making and reinforcement learning.
AB  - Negative symptoms are a core clinical feature of schizophrenia, but conceptual
      and methodological problems with current instruments can make their assessment
      challenging. One hypothesis is that current symptom assessments may be influenced
      by impairments in memory and may not be fully reflective of actual functioning
      outside of the laboratory. The present study sought to investigate the validity
      of assessing negative symptoms using ecological momentary assessment (EMA).
      Participants with schizophrenia (N = 31) completed electronic questionnaires on
      smartphones 4 times a day for 1 week. Participants also completed effort-based
      decision making and reinforcement learning (RL) tasks to assess the relationship
      between EMA and laboratory measures, which tap into negative symptom relevant
      domains. Hierarchical linear modeling analyses revealed that clinician-rated and
      self-report measures of negative symptoms were significantly related to negative
      symptoms assessed via EMA. However, working memory moderated the relationship
      between EMA and retrospective measures of negative symptoms, such that there was
      a stronger relationship between EMA and retrospective negative symptom measures
      among individuals with better working memory. The authors also found that
      negative symptoms assessed via EMA were related to poor performance on the effort
      task, whereas clinician-rated symptoms and self-reports were not. Further, they
      found that negative symptoms were related to poorer performance on learning
      reward contingencies. The findings suggest that negative symptoms can be assessed
      through EMA and that working memory impairments frequently seen in schizophrenia
      may affect recall of symptoms. Moreover, these findings suggest the importance of
      examining the relationship between laboratory tasks and symptoms assessed during
      daily life. (PsycINFO Database Record

PMID- 27893231
TI  - Trajectories of higher- and lower-order dimensions of negative and positive
      affect relative to restrictive eating in anorexia nervosa.
AB  - Despite robust support for the role of affect in the maintenance of binge eating
      and purging, the relationship between affect and restrictive eating remains
      poorly understood. To investigate the relationship between restrictive eating and
      affect, ecological momentary assessment data from 118 women with anorexia nervosa
      (AN) were used to examine trajectories of higher-order dimensions of negative
      affect (NA) and positive affect (PA), as well as lower-order dimensions of NA
      (Fear, Guilt) and PA (Joviality, Self-Assurance) relative to restrictive eating.
      Affect trajectories were modeled before and after restrictive eating episodes and
      AN subtype was examined as a moderator of these trajectories. Across the sample,
      Guilt significantly increased before and decreased after restrictive eating
      episodes. Global NA, Global PA, Fear, Joviality, and Self-Assurance did not vary
      relative to restrictive eating episodes across the sample. However, significant
      subtype by trajectory interactions were detected for PA indices. Among
      individuals with AN restricting subtype, Global PA, Joviality, and Self-Assurance
      decreased prior to and Self-Assurance increased following restrictive eating
      episodes. In contrast, Global PA and Self-Assurance increased prior to, but did
      not change following, restrictive eating episodes among individuals with AN binge
      eating/purging subtype. Results suggest that dietary restriction may function to
      mitigate guilt across AN subtypes and to enhance self-assurance among individuals
      with AN restricting subtype. (PsycINFO Database Record

PMID- 27893233
TI  - Trajectories of victimization in ethnic diaspora immigrant and native
      adolescents: Separating acculturation from development.
AB  - This longitudinal study aimed to differentiate between acculturative and
      developmental processes by (a) comparing levels and change rates in victimization
      among ethnic German immigrants and native German adolescents in Germany and
      Russian Jewish immigrants in Israel, and (b) testing whether interindividual
      differences in victimization among immigrant youth can be explained by the same
      general factors as in native groups or by migration-specific factors. In
      addition, we tested whether or not acculturative and developmental processes
      interact. The sample comprised 1,300 ethnic German immigrants, 820 native German
      adolescents, and 1,535 Russian Jewish adolescents. The participants (15.36-years
      old) completed 3 annual assessments. Two-part latent growth models showed similar
      levels and rates of change among all 3 ethnic groups. Interindividual differences
      in victimization were largely explained by the same general factors across all
      ethnic groups but acculturation-related hassles explained additional variance
      among immigrant youth. Acculturation and development interacted such that the
      protective effect of age did not set in until 3-5 years of residence among both
      immigrant groups. Results suggest that developmental pathways to victimization
      are very similar among immigrant and native youth once immigrants successfully
      have managed the phase transition of resettlement. (PsycINFO Database Record

PMID- 27893234
TI  - Mindful parenting predicts mothers' and infants' hypothalamic-pituitary-adrenal
      activity during a dyadic stressor.
AB  - Mindfulness in the parenting relationship has been proposed to help both parents
      and children better regulate stress, though this has not yet been shown at the
      physiological level. In this study, we tested relations between maternal
      mindfulness in parenting and both mothers' and their infants' hypothalamic
      pituitary-adrenal (HPA) axis activity during a dyadic stressor 3 months later.
      Participants were 73 mother-infant dyads from a larger longitudinal study. At 3
      months postpartum, mothers completed self-report measures of general
      dispositional mindfulness and parenting-specific mindfulness, as well as
      stressful life events. At 6 months postpartum, mother-infant dyads completed the
      Still Face task. Four saliva samples were collected from each dyad member for
      cortisol assay to index the HPA axis response. Hierarchical linear modeling of
      cortisol trajectories revealed a main effect of maternal parenting-specific
      mindfulness (mindful parenting), but not general dispositional mindfulness, on
      mothers' cortisol; mothers with higher mindful parenting showed steeper cortisol
      recovery slopes. In addition, maternal mindful parenting moderated the effect of
      life stress on later mother and infant cortisol. In the context of high life
      stress, maternal mindful parenting predicted lower infant cortisol levels, but
      more extended maternal cortisol elevations. Implications for a biobehavioral
      model of mindful parenting are discussed. (PsycINFO Database Record

PMID- 27893235
TI  - Age-related differences in audiovisual interactions of semantically different
      stimuli.
AB  - Converging results have shown that adults benefit from congruent multisensory
      stimulation in the identification of complex stimuli, whereas the developmental
      trajectory of the ability to integrate multisensory inputs in children is less
      well understood. In this study we explored the effects of audiovisual semantic
      congruency on identification of visually presented stimuli belonging to different
      categories, using a cross-modal approach. Four groups of children ranging in age
      from 6 to 13 years and adults were administered an object identification task of
      visually presented pictures belonging to living and nonliving entities. Stimuli
      were presented in visual, congruent audiovisual, incongruent audiovisual, and
      noise conditions. Results showed that children under 12 years of age did not
      benefit from multisensory presentation in speeding up the identification. In
      children the incoherent audiovisual condition had an interfering effect,
      especially for the identification of living things. These data suggest that the
      facilitating effect of the audiovisual interaction into semantic factors
      undergoes developmental changes and the consolidation of adult-like processing of
      multisensory stimuli begins in late childhood. (PsycINFO Database Record

PMID- 27893236
TI  - Training in the adolescent brain: An fMRI training study on divergent thinking.
AB  - Prior research suggests that adolescence is a time of enhanced sensitivity for
      practice and learning. In this study we tested the neural correlates of divergent
      thinking training in 15- to 16-year-old adolescents relative to an age-matched
      active control group. All participants performed an alternative uses task, a
      valid measure to test divergent thinking, while functional magnetic resonance
      imaging (fMRI) images were acquired before and after a training program. In
      between the 2 scanning sessions the experimental group completed 2 weeks of
      divergent thinking training (8 sessions) and the control group completed 2 weeks
      of rule switching training (8 session). A Group * Time interaction demonstrated
      stable divergent thinking performance for the experimental group, whereas in the
      control group performance declined. Generating alternative uses (experimental
      task condition) relative to generating ordinary characteristics of objects
      (control task condition) was associated with increased activation in the
      supramarginal gyrus (SMG), angular gyrus (AG), and middle temporal gyrus (MTG).
      Test-retest analyses showed that within-individuals-activation in these regions
      was stable over time in both groups. Changes in alternative uses fluency over
      time, however, were positively associated with changes in superior lateral PFC
      activation over time. Together, the results indicate that core brain regions for
      creativity (SMG, AG, and MTG) are consistently recruited in adolescence, and that
      changes in performance are associated with changes in activation in lateral PFC.
      (PsycINFO Database Record

PMID- 27893237
TI  - Emergence of Japanese infants' prosodic preferences in infant-directed
      vocabulary.
AB  - The article examines the role of infant-directed vocabulary (IDV) in infants
      language acquisition, specifically addressing the question of whether IDV forms
      that are not prominent in adult language may nonetheless be useful to the process
      of acquisition. Japanese IDV offers a good test case, as IDV characteristically
      takes a bisyllabic H(eavy)-L(ight) form that is rare in adult speech. In 5
      experiments using the Headturn Preference Procedure (HPP), 8- to 10-month-old
      Japanese infants, but not 4- to 6-month-olds, were found to show a preference for
      bisyllabic H-L words over other types of words. These results demonstrate (a)
      that infants may develop a preference for a dominant prosodic form based on
      infant-directed speech, even when it is not a prominent characteristic of adult
      language; and perhaps more importantly, and (b) that infant-directed speech may
      provide a boost for a feature that could be useful for infants' acquisition of
      language even when it not prominent in adult language. (PsycINFO Database Record

PMID- 27893238
TI  - Does anger regulation mediate the discrimination-mental health link among Mexican
      origin adolescents? A longitudinal mediation analysis using multilevel modeling.
AB  - [Correction Notice: An Erratum for this article was reported in Vol 53(2) of
      Developmental Psychology (see record 2017-04475-001). In the article, there were
      several typographical errors in the Recruitment and Procedures section. The
      percentage of mothers who responded to survey items should have been 99.3%.
      Additionally, the youths surveyed at T2 and T3 should have been n 246.
      Accordingly, the percentage of youths surveyed in T2 and T3 should have been
      91.4% and the percentage of mothers surveyed at T2 and T3 should have been 90.7%.
      Finally, the youths missing at T2 should have been n 23, and therefore the
      attrition rate for youth participants should have been 8.6. All versions of this
      article have been corrected.] Although prior research has consistently documented
      the association between racial/ethnic discrimination and poor mental health
      outcomes, the mechanisms that underlie this link are still unclear. The present 3
      wave longitudinal study tested the mediating role of anger regulation in the
      discrimination-mental health link among 269 Mexican-origin adolescents (Mage =
      14.1 years, SD = 1.6; 57% girls), 12 to 17 years old. Three competing anger
      regulation variables were tested as potential mediators: outward anger
      expression, anger suppression, and anger control. Longitudinal mediation analyses
      were conducted using multilevel modeling that disaggregated within-person effects
      from between-person effects. Results indicated that outward anger expression was
      a significant mediator; anger suppression and anger control were not significant
      mediators. Within a given individual, greater racial/ethnic discrimination was
      associated with more frequent outward anger expression. In turn, more frequent
      outward anger expression was associated with higher levels of anxiety and
      depression at a given time point. Gender, age, and nativity status were not
      significant moderators of the hypothesized mediation models. By identifying
      outward anger expression as an explanatory mechanism in the discrimination
      distress link among Latino youths, this study points to a malleable target for
      prevention and intervention efforts aimed at mitigating the detrimental impact of
      racism on Latino youths' mental health during the developmentally critical period
      of adolescence. (PsycINFO Database Record

PMID- 27893240
TI  - Is recovery possible outside the financial mainstream?
AB  - As psychiatric rehabilitation practitioners, we have solid evidence that our
      field's services are effective in helping people become employed, participate in
      social and civic life, avoid restrictive and coercive psychiatric treatment, and
      thrive in stable and secure community residences. Yet, hundreds of thousands of
      people with psychiatric disabilities do not do these things. So we must ask
      ourselves, to what extent is this due to their location outside the financial
      mainstream, and if it is, what we can do as a field to address poverty among
      those we serve? This editorial addresses this question: Is recovery possible
      outside of the financial mainstream? (PsycINFO Database Record

PMID- 27893241
TI  - Ill or injured: Shifting the emphasis to trauma in mental health diagnosis and
      treatment.
AB  - TOPIC: This contribution examines the disparity that exists between research that
      identifies the prevalence of trauma among mental health service users and the low
      frequency of adequately diagnosing and treating trauma in practice. For this
      author, the important question to pose is "Could behavioral health services be
      persistently erring in both diagnoses and treatment approaches to adequately
      assist and support service users?" PURPOSE: The author proposes an alternative
      service model which is aligned with the prevalence of complex trauma. Data is
      presented that supports the high incidence of trauma among service users as well
      as the historical efficacy of relationship-based treatment. SOURCES USED:
      Personal experience is shared in conjunction with an overview of research in
      support of the prevalence of trauma and the efficacy of relationship-based
      treatment. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Shifting our diagnostic
      focus away from biomedical illness to be inclusive of trauma-based, developmental
      injury will align mental health and rehabilitation practice more adequately with
      research and encourage improved diagnostic accuracy and a shift toward
      relationship-based treatment interventions, thereby hopefully improving outcomes
      for our service recipients. (PsycINFO Database Record

PMID- 27893239
TI  - Face-blind for other-race faces: Individual differences in other-race recognition
      impairments.
AB  - We report the existence of a previously undescribed group of people, namely
      individuals who are so poor at recognition of other-race faces that they meet
      criteria for clinical-level impairment (i.e., they are "face-blind" for other
      race faces). Testing 550 participants, and using the well-validated Cambridge
      Face Memory Test for diagnosing face blindness, results show the rate of other
      race face blindness to be nontrivial, specifically 8.1% of Caucasians and Asians
      raised in majority own-race countries. Results also show risk factors for other
      race face blindness to include: a lack of interracial contact; and being at the
      lower end of the normal range of general face recognition ability (i.e., even for
      own-race faces); but not applying less individuating effort to other-race than
      own-race faces. Findings provide a potential resolution of contradictory evidence
      concerning the importance of the other-race effect (ORE), by explaining how it is
      possible for the mean ORE to be modest in size (suggesting a genuine but minor
      problem), and simultaneously for individuals to suffer major functional
      consequences in the real world (e.g., eyewitness misidentification of other-race
      offenders leading to wrongful imprisonment). Findings imply that, in legal
      settings, evaluating an eyewitness's chance of having made an other-race
      misidentification requires information about the underlying face recognition
      abilities of the individual witness. Additionally, analogy with prosopagnosia
      (inability to recognize even own-race faces) suggests everyday social
      interactions with other-race people, such as those between colleagues in the
      workplace, will be seriously impacted by the ORE in some people. (PsycINFO
      Database Record

PMID- 27893242
TI  - Work-based learning: A training model for state wide system changes.
AB  - TOPIC: Despite the substantial amount of money invested in staff training each
      year, many people trained fail to transfer what they learn to the workplace. We
      document a training initiative that was implemented to develop and maintain a
      competent workforce. PURPOSE: A work-based learning (WBL) model was used as a
      guide to teach the knowledge and skills necessary to effectively deliver
      psychiatric rehabilitation services. SOURCES USED: This training framework
      afforded practitioners an opportunity to acquire the critical knowledge and
      skills to improve the quality of life for individuals living with serious mental
      illnesses. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Preliminary pre and
      posttest results show an overall increase in practitioner knowledge.
      Additionally, individualized technical assistance has the potential to increase
      positive learning outcomes. (PsycINFO Database Record

PMID- 27893243
TI  - Adolescent psychosocial development: A review of longitudinal models and
      research.
AB  - This review used 4 types of longitudinal models (descriptive models, prediction
      models, developmental sequence models and longitudinal mediation models) to
      identify regular patterns of psychosocial development in adolescence. Eight
      patterns of adolescent development were observed across countries: (1) adolescent
      maturation in multiple developmental domains; (2) heterogeneous continuity of
      personal relationships; (3) good goes together with good, and bad with bad,
      across time in adolescence; (4) parents transmit values and behaviors to their
      adolescent children over time; (5) adolescent psychopathology leads to erosion of
      personal relationships with parents and peers; (6) adolescent psychopathology
      prevents adolescent independence from parents; (7) parental interference in
      personal issues of adolescents has counterproductive effects over time; (8) mood
      variability and (social and personal) uncertainty are mechanisms that maintain
      psychopathology in adolescence. Principles of life span developmental psychology
      are used to discuss adolescent maturation, and a developmental contextual
      perspective is used to discuss links between the various developmental patterns.
      Strengths and limitations of the various longitudinal models, and links between
      longitudinal and experimental research are discussed. (PsycINFO Database Record

PMID- 27893244
TI  - Temporal ordering effects of adolescent depression, relational aggression, and
      victimization over six waves: Fully latent reciprocal effects models.
AB  - The temporal ordering of depression, aggression, and victimization has important
      implications for theory, policy, and practice. For a representative sample of
      high school students (Grades 7-10; N = 3,793) who completed the same
      psychometrically strong, multiitem scales 6 times over a 2-year period, there
      were reciprocal effects between relational-aggression and relational
      victimization factors: aggression led to subsequent victimization and
      victimization led to subsequent aggression. After controlling for prior
      depression, aggression, and victimization, depression had a positive effect on
      subsequent victimization, but victimization had no effect on subsequent
      depression. Aggression neither affected nor was affected by depression. The
      results suggest that depression is a selection factor that leads to
      victimization, but that victimization has little or no effect on subsequent
      depression beyond what can be explained by the preexisting depression. In support
      of developmental equilibrium, the results were consistent across the 6 waves.
      (PsycINFO Database Record

PMID- 27893245
TI  - The quest for identity in adolescence: Heterogeneity in daily identity formation
      and psychosocial adjustment across 5 years.
AB  - Identity formation is one of the key developmental tasks in adolescence.
      According to Erikson (1968) experiencing identity uncertainty is normative in
      adolescence. However, empirical studies investigating identity uncertainty on a
      daily basis are lacking. Hence, studying individual differences in daily
      certainty (i.e., identity commitment levels) and uncertainty (i.e., identity
      commitment fluctuations and identity reconsideration) in the identity formation
      process may advance our knowledge about the extent to which adolescents' identity
      uncertainty is part of normative identity development. Therefore, this
      longitudinal study examined heterogeneity in certainty and uncertainty dynamics
      of adolescents' daily identity formation using a longitudinal microlevel
      approach. Dutch adolescents (N = 494; Mage = 13.03 years at T1; 56.7% boys)
      reported on 2 key dimensions of identity formation (i.e., commitment and
      reconsideration) in both the educational and interpersonal domain on a daily
      basis for 3 weeks within 1 year, across 5 successive years. Multivariate latent
      class growth analyses suggested both in the educational and interpersonal
      identity domain a class of adolescents displaying a "crisis-like" identity
      formation process, and an "identity synthesis" class. Classes revealed
      differential development of (global and school) anxiety, aggression, and best
      friend support. Taken together, the present study confirmed Erikson's notion that
      experiencing daily identity uncertainty is common during adolescence. However, a
      substantial amount of adolescents also showed a process toward identity
      maturation already during adolescence. (PsycINFO Database Record

PMID- 27893246
TI  - The unique roles of intrapersonal and social factors in adolescent smoking
      development.
AB  - Adolescence is a vulnerable period for the initiation and peak of many harmful
      risk-taking behaviors such as smoking, which is among the most addictive and
      deadliest behaviors. Generic metatheories like the theory of triadic influence
      (TTI) suggest that interrelated risk factors across multiple domains (i.e.,
      intrapersonal and social/environmental) jointly contribute to adolescent smoking
      behavior. Yet, studies are lacking that investigate risk factors across different
      domains in the same study, which obscures whether each makes a unique
      contribution to the increase in smoking throughout adolescence or whether there
      is overlap across the domains. Hence, to fill this gap using a latent growth
      approach, the current accelerated longitudinal study investigated the collective
      contribution of multiple intrapersonal and social risk factors in the development
      of smoking behavior from ages 12 to 17 in 574 ethnically diverse Dutch
      adolescents. Results from the latent growth model showed that whereas the
      contribution of motivational-intrapersonal factors like sensation-seeking was no
      longer significant in the stringent multivariate model, higher levels of
      impulsivity (cognitive-intrapersonal) and overt peer pressure (social) at age 12
      proved to be robust and unique predictors of linear increases in adolescent
      smoking up until age 17. Consistent with the TTI, adolescent smoking progression
      does not occur in isolation and the determinants are wide-ranging as they stem
      from both intrapersonal and social domains. Thus focusing on such confluence of
      intrapersonal and social risk factors via prevention programs from as young as
      age 12 might halt the deadly increase in smoking behavior throughout adolescence.
      (PsycINFO Database Record

PMID- 27893247
TI  - What drives developmental change in adolescent disclosure and maternal knowledge?
      Heterogeneity in within-family processes.
AB  - This study aimed to gain a better understanding of the normative declines in
      adolescent disclosure and maternal knowledge over the course of adolescence, by
      assessing the underlying monitoring processes. Multilevel structural equation
      models were applied to 15 assessments among 479 families across 5 years (13 years
      at T1, 57% boys, 11% low socioeconomic status). Developmental declines in mother
      perceived disclosure and knowledge were observed, which were partially explained
      by processes operating at the level of the family unit. On average, mothers were
      more knowledgeable in weeks with more disclosure and more solicitation, and
      adolescent disclosure was higher in weeks with more maternal solicitation and
      less control. The effect sizes and even the directions of these within-family
      correlations varied between families, however. This heterogeneity was partially
      explained by the level of maternal control and adolescent disclosure, and by the
      families' socioeconomic status. Within-family fluctuations in knowledge and
      disclosure were also correlated with fluctuations in relationship quality and
      adolescent and mother mood. Overall, these within-family processes explained up
      to 14% of the normative developmental decline in disclosure and 19% of the
      decline in knowledge. This study thus suggests that a wide variety in monitoring
      processes may drive normative declines in adolescent disclosure and maternal
      knowledge. (PsycINFO Database Record

PMID- 27893248
TI  - Can student engagement serve as a motivational resource for academic coping,
      persistence, and learning during late elementary and early middle school?
AB  - How children and youth deal with academic challenges and setbacks can make a
      material difference to their learning and school success. Hence, it is important
      to investigate the factors that allow students to cope constructively. A process
      model focused on students' motivational resources was used to frame a study
      examining whether engagement in the classroom shapes students' academic coping,
      and whether coping in turn contributes to subsequent persistence on challenging
      tasks and learning, which then feed back into ongoing engagement. In fall and
      spring of the same school year, 880 children in 4th through 6th grades and their
      teachers completed measures of students' engagement and disaffection in the
      classroom, and of their re-engagement in the face of obstacles and difficulties;
      students also reported on 5 adaptive and 6 maladaptive ways of academic coping;
      and information on a subset of students' classroom grades was collected.
      Structural analyses, incorporating student-reports, teacher-reports, and their
      combination, indicated that the model of motivational processes was a good fit
      for time-ordered data from fall to spring. Multiple regressions examining each
      step in the process model also indicated that it was the profile of coping
      responses, rather than any specific individual way of coping, that was most
      centrally connected to changes in engagement and persistence. Taken together,
      findings suggest that these internal dynamics may form self-perpetuating cycles
      that could cement or augment the development of children's motivational
      resilience and vulnerability across time. (PsycINFO Database Record

PMID- 27893249
TI  - Sleep spindles and intelligence in early childhood-developmental and trait
      dependent aspects.
AB  - Sleep spindles act as a powerful marker of individual differences in cognitive
      ability. Sleep spindle parameters correlate with both age-related changes in
      cognitive abilities and with the age-independent concept of IQ. While some
      studies have specifically demonstrated the relationship between sleep spindles
      and intelligence in young children, our previous work in older subjects revealed
      sex differences in the sleep spindle correlates of IQ, which was never
      investigated in small children before. We investigated the relationship between
      age, Raven Colored Progressive Matrices (CPM) scores and sleep spindles in 28
      young children (age 4-8 years, 15 girls). We specifically investigated sex
      differences in the psychometric correlates of sleep spindles. We also aimed to
      separate the correlates of sleep spindles that are because of age-related
      maturation from other effects that reflect an age-independent relationship
      between sleep spindles and general intelligence. Our results revealed a modest
      positive correlation between fast spindle amplitude and age. Raven CPM scores
      positively correlated with both slow and fast spindle amplitude, but this effect
      remained a tendency in males and vanished after correcting for the effects of
      age. Age-corrected correlations between Raven CPM scores and both slow and fast
      spindle amplitude were only significant in females. Overall, our results show
      that in male children sleep spindles are a maturational marker, but in female
      children they indicate trait-like intelligence, in line with previous studies in
      adolescent and adult subjects. Thalamocortical white matter connectivity may be
      the underlying mechanism behind both higher spindle amplitude and higher
      intelligence in female, but not male subjects. (PsycINFO Database Record

PMID- 27893250
TI  - Variation in impacts of Tulsa pre-K on cognitive development in kindergarten: The
      role of instructional support.
AB  - Public prekindergarten (pre-K) programs have been a recent focus of policy and
      research attention, in part because of their empirically documented, positive
      short-term impacts on child cognitive development and school readiness. However,
      no studies have explored factors that might explain variation across schools in
      public pre-K impacts. The current study examines the Tulsa Public School pre-K
      program's impacts on children's letter-word identification, spelling, and applied
      problem-solving skills at kindergarten entry. Findings reveal substantial across
      school variation in treatment impacts, associated with variation in instructional
      support. Results are robust to sensitivity checks and are discussed alongside
      implications for policy and future research. (PsycINFO Database Record

PMID- 27893251
TI  - Sources of developmental change in the efficiency of information search.
AB  - Children are active learners: they learn not only from the information people
      offer and the evidence they happen to observe, but by actively seeking
      information. However, children's information search strategies are typically less
      efficient than those of adults. In two studies, we isolate potential sources of
      developmental change in how children (7- and 10-year-olds) and adults search for
      information. To do so, we develop a hierarchical version of the 20-questions
      game, in which participants either ask questions (Study 1) or test individual
      objects (Study 2) to discover which category of objects within a nested structure
      (e.g., animals, birds, or owls) has a novel property. We also develop a
      computational model of the task, which allows us to evaluate performance in
      quantitative terms. As expected, we find developmental improvement in the
      efficiency of information search. In addition, we show that participants'
      performance exceeds random search, but falls short of optimal performance. We
      find mixed support for the idea that children's inefficiency stems from
      difficulty thinking beyond the level of individual objects or hypotheses.
      Instead, we reveal a previously undocumented source of developmental change:
      Children are significantly more likely than adults to continue their search for
      information beyond the point at which a single hypothesis remains, and thus to
      ask questions and select objects associated with zero information gain. This
      suggests that one crucial source of developmental change in information search
      efficiency lies in children's "stopping rules." (PsycINFO Database Record

PMID- 27893252
TI  - Developing knowledge of nonadjacent dependencies.
AB  - Characterizing the nature of linguistic representations and how they emerge
      during early development is a central goal in the cognitive science of language.
      One area in which this development plays out is in the acquisition of
      dependencies-relationships between co-occurring elements in a word, phrase, or
      sentence. These dependencies often involve multiple levels of representation and
      abstraction, built up as infants gain experience with their native language. The
      authors used the Headturn Preference Procedure to systematically investigate the
      early acquisition of 1 such dependency, the agreement between a subject and verb
      in French, at 6 different ages between 14 and 24 months. The results reveal a
      complex developmental trajectory that provides the first evidence that infants
      might indeed progress through distinct stages in the acquisition of this
      nonadjacent dependency. The authors discuss how changes in general cognition and
      representational knowledge (from reflecting surface statistics to higher-level
      morphological features) might account for their findings. These findings
      highlight the importance of studying language acquisition at close time intervals
      over a substantial age range. (PsycINFO Database Record

PMID- 27893253
TI  - Perception of visual-tactile colocation in the first year of life.
AB  - An ability to perceive tactile and visual stimuli in a common spatial frame of
      reference is a crucial ingredient in forming a representation of one's own body
      and the interface between bodily and external space. In this study, the authors
      investigated young infants' abilities to perceive colocation between tactile and
      visual stimuli presented on the hands. They examined infants' visual preferences
      for spatially congruent and incongruent visual-tactile events across two age
      groups (6 months and 10-months). They observed increased duration of looking to
      incongruent stimuli displays in both age groups, indicating that infants from at
      least 6 months of age demonstrate the ability to determine whether simultaneously
      presented visual-tactile perceptual events are colocated or not. These findings
      indicate that an ability to perceive visual and tactile stimuli within a common
      spatial frame of reference is available by the end of the first half year of
      life. (PsycINFO Database Record

PMID- 27893254
TI  - Dynamic interplay between merger process justice and cognitive trust in top
      management: A longitudinal study.
AB  - This study examines two fundamental concerns in the context of organizational
      change: employees' perceptions of merger process justice and cognitive trust in
      the top management team. Our main purpose is to better understand the nature of
      reciprocal relations between these important constructs through a significant
      change event. Previous research, building mainly on social exchange theory, has
      framed trust as a consequence of justice perceptions. More recently, scholars
      have suggested that this view may be overly simplistic and that trust-related
      cognitions may also represent an important antecedent of justice perceptions.
      Using 3-wave longitudinal survey data (N = 622) gathered during a merger process,
      we tested reciprocal relations over time between cognitive trust in the top
      management team and perceptions of the merger process justice. In contrast to the
      conventional unidirectional notion of trust or trust-related cognitions as
      outcomes of perceived justice, our results show positive reciprocal relations
      over time between cognitive trust and justice. Our findings also revealed that
      the positive influence of cognitive trust on subsequent justice perceptions was
      slightly more robust than the opposite direction. By examining cross-lagged
      longitudinal relations between these critical psychological reactions, this study
      contributes across multiple domains of the management literature including trust,
      justice, and organizational mergers. (PsycINFO Database Record

PMID- 27893255
TI  - The relationship between sleep and work: A meta-analysis.
AB  - Sleep has tremendous importance to organizations because of its relationship with
      employee performance, safety, health, and attitudes. Moreover, sleep is a
      malleable behavior that may be improved by individual and organizational changes.
      Despite the consequential and modifiable nature of sleep, little consensus exists
      regarding its conceptualization, and how the choice of conceptualization may
      impact relationships with organizational antecedents and outcomes. To offer a
      stronger foundation for future theory and research about employee sleep, this
      study calculated meta-analytic correlations of sleep quality and sleep quantity
      from 152 primary studies of sleep among workers in organizations. Analyses
      revealed that both sleep quality and sleep quantity associated negatively with
      workload and a number of health, attitudinal, and affective outcomes. Despite
      their conceptual similarity, notable differences existed in sleep quality and
      sleep quantity in terms of their relationships to many different correlates.
      Generally, the relationships between sleep quality and the examined correlates
      were stronger for variables that reflected perceptions. Moderator analyses showed
      that relationships between sleep quality and quantity may be affected by
      measurement method and the number of self-report items used, while there is
      little evidence of the effect of measurement time frame. Findings from this first
      meta-analytic investigation of the occupational sleep literature have
      implications for the development of theory about relationships between sleep and
      work, the measurement of sleep, the identification of organizational correlates
      of sleep, and the design of interventions intended to improve employee sleep.
      (PsycINFO Database Record

PMID- 27893256
TI  - Sticks and stones can break my bones but words can also hurt me: The relationship
      between customer verbal aggression and employee incivility.
AB  - Customer service employees tend to react negatively to customer incivility by
      demonstrating incivility in return, thereby likely reducing customer service
      quality. Research, however, has yet to uncover precisely what customers do that
      results in employee incivility. Through transcript and computerized text analysis
      in a multilevel, multisource, mixed-method field study of customer service events
      (N = 434 events), we found that employee incivility can occur as a function of
      customer (a) aggressive words, (b) second-person pronoun use (e.g., you, your),
      (c) interruptions, and (d) positive emotion words. First, the positive
      association between customer aggressive words and employee incivility was more
      pronounced when the verbal aggression included second-person pronouns, which we
      label targeted aggression. Second, we observed a 2-way interaction between
      targeted aggression and customer interruptions such that employees demonstrated
      more incivility when targeted customer verbal aggression was accompanied by more
      (vs. fewer) interruptions. Third, this 2-way interaction predicting employee
      incivility was attenuated when customers used positive emotion words. Our results
      support a resource-based explanation, suggesting that customer verbal aggression
      consumes employee resources potentially leading to self-regulation failure,
      whereas positive emotion words from customers can help replenish employee
      resources that support self-regulation. The present study highlights the
      advantages of examining what occurs within customer-employee interactions to gain
      insight into employee reactions to customer incivility. (PsycINFO Database Record

PMID- 27893257
TI  - Is it new? Personal and contextual influences on perceptions of novelty and
      creativity.
AB  - Novelty recognition is the crucial starting point for extracting value from the
      ideas generated by others. In this paper we develop an associative evaluation
      account for how personal and contextual factors motivate individuals to perceive
      novelty and creativity. We report 4 studies that systematically tested hypotheses
      developed from this perspective. Study 1 (a laboratory experiment) showed that
      perceivers' regulatory focus, as an experimentally induced state, affected
      novelty perception. Study 2 (a field study) found that perceivers' promotion
      focus and prevention focus, measured as chronic traits, each interacted with
      normative level of novelty and creativity: perceivers who scored higher on
      promotion focus perceived more novelty (or creativity) in novel (or creative)
      targets than those who scored lower, whereas perceivers who scored higher on
      prevention focus perceived less novelty (or creativity) in novel (or creative)
      targets than those who scored lower. Study 3 (a field study) showed that
      organizational culture affected the perception of novelty and creativity. Study 4
      (a laboratory experiment) found perceiver-by-idea-by-context 3-way interaction
      effects: for perceivers with prevention focus, the positive relation between
      normative level of novelty and novelty ratings was weakened in the loss-framing
      condition versus the gain-framing condition. We discuss implications of the
      findings for future research and management practice. (PsycINFO Database Record

PMID- 27893258
TI  - The rich get richer and the poor get poorer: Country- and state-level income
      inequality moderates the job insecurity-burnout relationship.
AB  - Despite the prevalence of income inequality in today's society, research on the
      implications of income inequality for organizational research is scant. This
      study takes the first step to explore the contextual role of national- and state-
      level income inequality as a moderator in the relationship between individual
      level job insecurity (JI) and burnout. Drawing from conservation of resource
      (COR) theory, we argue that income inequality at the country-level and state
      level threatens one's obtainment of object (i.e., material coping) and condition
      (i.e., nonmaterial coping) resources, thus serving as an environmental stressor
      exacerbating one's burnout reactions to JI. The predicted cross-level interaction
      effect of income inequality was tested in 2 studies. Study 1 consisting of 23,778
      individuals nested in 30 countries explored the moderating effect of country
      level income inequality on the relationship between individual JI and exhaustion.
      Study 2 collected data from 402 employees residing in 48 states in the United
      States, and tested the moderating effect of state-level income inequality on the
      relationship between JI and burnout (i.e., emotional exhaustion and cynicism).
      Results of both studies converge to support the exacerbating role of higher-level
      income inequality on the JI -burnout relationship. Our findings contribute to the
      literature on psychological health disparities by exploring the contextual role
      of income inequality as a predictor of differential reactions to JI. (PsycINFO
      Database Record

PMID- 27893259
TI  - Adolescent conscientiousness predicts lower lifetime unemployment.
AB  - Existing research on Big Five personality and unemployment has relied on
      personality measures elicited after the respondents had already spent years in
      the labor market, an experience that could change personality. We clarify the
      direction of influence by using the British Cohort Study (N = 4,206) to examine
      whether conscientiousness and other Big Five personality traits at age 16-17
      predict unemployment over age 16-42. Our hypothesis that higher conscientiousness
      in adolescence would predict lower unemployment was supported. In analyses
      controlling for intelligence, gender, and parental socioeconomic status, the less
      conscientious (-1 SD) had a predicted probability of unemployment twice as high
      (3.4% vs. 1.7%) as the highly conscientious (+1 SD), an effect size comparable to
      intelligence. Mediation analysis revealed that academic motivation and
      educational attainment explained only 8.9% of this association. Fostering
      conscientiousness in early life may be an effective way to reduce unemployment
      throughout adulthood. (PsycINFO Database Record

PMID- 27893260
TI  - Brain drain? An examination of stereotype threat effects during training on
      knowledge acquisition and organizational effectiveness.
AB  - Stereotype threat describes a situation in which individuals are faced with the
      risk of upholding a negative stereotype about their subgroup based on their
      actions. Empirical work in this area has primarily examined the impact of
      negative stereotypes on performance for threatened individuals. However, this
      body of research seldom acknowledges that performance is a function of learning
      which may also be impaired by pervasive group stereotypes. This study presents
      evidence from a 3-day self-guided training program demonstrating that stereotype
      threat impairs acquisition of cognitive learning outcomes for females facing a
      negative group stereotype. Using hierarchical Bayesian modeling, results revealed
      that stereotyped females demonstrated poorer declarative knowledge acquisition,
      spent less time reflecting on learning activities, and developed less efficiently
      organized knowledge structures compared with females in a control condition.
      Findings from a Bayesian mediation model also suggested that despite stereotyped
      individuals "working harder" to perform well, their underachievement was largely
      attributable to failures in learning to "work smarter." Building upon these
      empirical results, a computational model and computer simulation is also
      presented to demonstrate the practical significance of stereotype-induced
      impairments to learning on the development of an organization's human capital
      resources and capabilities. The simulation results show that even the presence of
      small effects of stereotype threat during learning/training have the potential to
      exert a significant negative impact on an organization's performance potential.
      Implications for future research and practice examining stereotype threat during
      learning are discussed. (PsycINFO Database Record

PMID- 27893261
TI  - Implementation of behavioral health interventions in real world scenarios:
      Managing complex change.
AB  - INTRODUCTION: A practice embarks on a radical reformulation of how care is
      designed and delivered when it decides to integrate medical and behavioral health
      care for its patients and success depends on managing complex change in a complex
      system. We examined the ways change is managed when integrating behavioral health
      and medical care. METHOD: Observational cross-case comparative study of 19
      primary care and community mental health practices. We collected mixed methods
      data through practice surveys, observation, and semistructured interviews. We
      analyzed data using a data-driven, emergent approach. RESULTS: The change
      management strategies that leadership employed to manage the changes of
      integrating behavioral health and medical care included: (a) advocating for a
      mission and vision focused on integrated care; (b) fostering collaboration, with
      a focus on population care and a team-based approaches; (c) attending to
      learning, which includes viewing the change process as continuous, and creating a
      culture that promoted reflection and continual improvement; (d) using data to
      manage change, and (e) developing approaches to finance integration. DISCUSSION:
      This paper reports the change management strategies employed by practice leaders
      making changes to integrate care, as observed by independent investigators. We
      offer an empirically based set of actionable recommendations that are relevant to
      a range of leaders (policymakers, medical directors) and practice members who
      wish to effectively manage the complex changes associated with integrated primary
      care. (PsycINFO Database Record

PMID- 27893263
TI  - "Incidental fear cues increase monetary loss aversion": Correction to Schulreich,
      Gerhardt, and Heekeren (2016).
AB  - Reports an error in "Incidental fear cues increase monetary loss aversion" by
      Stefan Schulreich, Holger Gerhardt and Hauke R. Heekeren (Emotion, 2016[Apr], Vol
      16[3], 402-412). In the current article, there was an error in the Study 2
      portion of the article. The fourth paragraph of the Results section should read
      as follows: Performing the same analyses as in Study 1, we found an effect of
      incidental fear cues on decision behavior. Participants accepted fewer gambles in
      the fearful-face condition (32.77%) than in the neutral-face condition (33.96%),
      with Z = -2.187, p = .027, d = -0.998 in the Wilcoxon signed-ranks test and beta
      = 0.012, SE = 0.0053, F(1, 21) = 4.434, p = .047, partial eta2 = .174 in the
      linear regression. This suggests increased risk aversion in the fearful-face
      condition. Concerning personality, however, there were no significant between
      subjects effects or between-within interaction effects (all ps = .349). (The
      following abstract of the original article appeared in record 2015-52358-001.) In
      many everyday decisions, people exhibit loss aversion-a greater sensitivity to
      losses relative to gains of equal size. Loss aversion is thought to be (at least
      partly) mediated by emotional-in particular, fear-related-processes. Decision
      research has shown that even incidental emotions, which are unrelated to the
      decision at hand, can influence decision making. The effect of incidental fear on
      loss aversion, however, is thus far unclear. In two studies, we experimentally
      investigated how incidental fear cues, presented during (Study 1) or before
      (Study 2) choices to accept or reject mixed gambles over real monetary stakes,
      influence monetary loss aversion. We find that the presentation of fearful faces,
      relative to the presentation of neutral faces, increased risk aversion-an effect
      that could be attributed to increased loss aversion. The size of this effect was
      moderated by psychopathic personality: Fearless dominance, in particular its
      interpersonal facet, but not self-centered impulsivity, attenuated the effect of
      incidental fear cues on loss aversion, consistent with reduced fear reactivity.
      Together, these results highlight the sensitivity of loss aversion to the
      affective context. (PsycINFO Database Record

PMID- 27893262
TI  - Reducing barriers to mental health care for student-athletes: An integrated care
      model.
AB  - Research suggests that National Collegiate Athletic Association (NCAA) Division I
      student-athletes have higher levels of stress and other behavioral health issues,
      including substance use, than nonathletes. For several reasons, student-athletes
      may be less likely to admit to behavioral health issues and seek mental health
      care. Integrated care is a model of care that integrates behavioral health into a
      medical practice. This article explores the newly released NCAA Best Mental
      Health Practice guidelines and the application of integrated care to a Division I
      athletic training room setting using the three-worldview framework for successful
      integration, incorporating clinical outcomes, operational reliability, and
      financial stability. (PsycINFO Database Record

PMID- 27893264
TI  - "Is supervision necessary? Examining the effects of Internet-based CBT training
      with and without supervision": Correction to Rakovshik et al. (2016).
AB  - : Reports an error in "Is supervision necessary? Examining the effects of
      internet-based CBT training with and without supervision" by Sarah G. Rakovshik,
      Freda McManus, Maria Vazquez-Montes, Kate Muse and Dennis Ougrin (Journal of
      Consulting and Clinical Psychology, 2016[Mar], Vol 84[3], 191-199). In the
      article, the department and affiliation were misspelled for author Kate Muse. The
      department and affiliation should have read Psychology Department, University of
      Worcester. All versions of this article has been corrected. (The following
      abstract of the original article appeared in record 2016-03513-001.) Objective:
      To investigate the effect of Internet-based training (IBT), with and without
      supervision, on therapists' (N = 61) cognitive-behavioral therapy (CBT) skills in
      routine clinical practice. METHOD: Participants were randomized into 3
      conditions: (1) Internet-based training with use of a consultation worksheet (IBT
      CW); (2) Internet-based training with CBT supervision via Skype (IBT-S); and (3)
      "delayed-training" controls (DTs), who did not receive the training until all
      data collection was completed. The IBT participants received access to training
      over a period of 3 months. CBT skills were evaluated at pre-, mid- and
      posttraining/wait using assessor competence ratings of recorded therapy sessions.
      RESULTS: Hierarchical linear analysis revealed that the IBT-S participants had
      significantly greater CBT competence at posttraining than did IBT-CW and DT
      participants at both the mid- and posttraining/wait assessment points. There were
      no significant differences between IBT-CW and the delayed (no)-training DTs.
      CONCLUSIONS: IBT programs that include supervision may be a scalable and
      effective method of disseminating CBT into routine clinical practice,
      particularly for populations without ready access to more-traditional "live"
      methods of training. There was no evidence for a significant effect of IBT
      without supervision over a nontraining control, suggesting that merely providing
      access to IBT programs may not be an effective method of disseminating CBT to
      routine clinical practice. (PsycINFO Database Record

PMID- 27893265
TI  - VA residential treatment providers' use of two evidence-based psychotherapies for
      PTSD: Global endorsement versus specific components.
AB  - OBJECTIVE: Despite a growing body of knowledge about the dissemination of
      evidence-based psychotherapies (EBPs), their actual use in clinical settings is
      not well understood. The purpose of the current study was to compare self
      reported component use with global use for 2 EBPs for posttraumatic stress
      disorder (PTSD), prolonged exposure (PE), and cognitive processing therapy (CPT).
      METHOD: Around 174 providers from 38 VA PTSD residential treatment programs were
      asked about both global use and component use of PE and CPT. RESULTS: Among
      frequent users of these EBPs, component use was generally high, especially for
      low-intensity and nonspecific components. For each form of treatment, there were
      a small number of providers who reported using the treatment frequently but did
      not use most of the key components of the treatment. CONCLUSIONS: These findings
      highlight the importance of understanding the modifications that providers make
      to EBPs and suggest the importance of flexibility within fidelity to these
      treatments. (PsycINFO Database Record

PMID- 27893266
TI  - Assessing civilian perceptions of combat veterans: An IAT study.
AB  - OBJECTIVE: Evidence suggests that civilians may have considerable ambivalence to
      returning veterans. While civilians are frequently grateful for the service of
      military personnel, they can often be wary of the mental health and stability of
      returning veterans. If civilians do hold such negative biases toward veterans,
      whether implicit or explicit, this may have a significant impact on the ability
      of military personnel to integrate back into society. The goal of the study was
      to test whether participants held an implicit bias of mental instability toward
      veterans. METHOD: In this study, 48 participants took an adapted version of the
      Implicit Association Test (IAT; Greenwald, McGhee, & Schwartz, 1998). Pictures of
      veterans and civilians were paired with words that either reflected mental
      stability (safe, sane, reliable, responsible) or instability (crazy, dangerous,
      unstable, unpredictable). RESULTS: The results demonstrated a finding of moderate
      effect size for an association between veterans and instability. Participants had
      significantly shorter response times (RTs) for IAT blocks in which veteran
      pictures and negative words were paired. CONCLUSIONS: This is the first study in
      the literature to demonstrate implicit biases of veterans as unstable. If
      implicit biases do in fact exist, the reintegration issues that veterans face may
      be due, at least in part, to a negative bias they face upon their return.
      (PsycINFO Database Record

PMID- 27893267
TI  - Identity adjustment among Afghanistan and Iraq war veterans with reintegration
      difficulty.
AB  - OBJECTIVE: To examine perceptions of identity adjustment in a diverse, national
      sample of U.S. veterans of the wars in Afghanistan and Iraq. METHOD: The authors
      conducted a planned thematic analysis of text written by Afghanistan and Iraq war
      veterans when they were asked to describe their reintegration difficulties as
      part of a randomized controlled trial (RCT) of online expressive writing (Sayer
      et al., 2015). Participants were 100 randomly selected veterans from the larger
      study (42 women and 58 men, 60 active duty and 38 reserves or National Guard).
      RESULTS: Nearly 2/3s of participants wrote about their identity adjustment. The 5
      interrelated areas of identity adjustment difficulty were (a) feeling like one
      does not belong in civilian society, (b) missing the military's culture and
      structured lifestyle, (c) holding negative views of civilian society, (d) feeling
      left behind compared to civilian counterparts due to military service, and (e)
      having difficulty finding meaning in the civilian world. The authors did not
      observe differences by gender. However, those deployed from active duty were
      particularly likely to feel as if they did not belong in civilian society and
      that they had not acquired needed skills, whereas those deployed from the
      reserves or National Guard experienced difficulty in reestablishing former
      civilian identities. CONCLUSIONS: Identity adjustment is a critical yet
      understudied aspect of veteran reintegration into community life following combat
      deployment. (PsycINFO Database Record

PMID- 27893268
TI  - Domain-general mechanisms for speech segmentation: The role of duration
      information in language learning.
AB  - Speech segmentation is supported by multiple sources of information that may
      either inform language processing specifically, or serve learning more broadly.
      The Iambic/Trochaic Law (ITL), where increased duration indicates the end of a
      group and increased emphasis indicates the beginning of a group, has been
      proposed as a domain-general mechanism that also applies to language. However,
      language background has been suggested to modulate use of the ITL, meaning that
      these perceptual grouping preferences may instead be a consequence of language
      exposure. To distinguish between these accounts, we exposed native-English and
      native-Japanese listeners to sequences of speech (Experiment 1) and nonspeech
      stimuli (Experiment 2), and examined segmentation using a 2AFC task. Duration was
      manipulated over 3 conditions: sequences contained either an initial-item
      duration increase, or a final-item duration increase, or items of uniform
      duration. In Experiment 1, language background did not affect the use of duration
      as a cue for segmenting speech in a structured artificial language. In Experiment
      2, the same results were found for grouping structured sequences of visual
      shapes. The results are consistent with proposals that duration information draws
      upon a domain-general mechanism that can apply to the special case of language
      acquisition. (PsycINFO Database Record

PMID- 27893269
TI  - Submentalizing or mentalizing in a Level 1 perspective-taking task: A cloak and
      goggles test.
AB  - It has been proposed that humans possess an automatic system to represent mental
      states ('implicit mentalizing'). The existence of an implicit mentalizing system
      has generated considerable debate however, centered on the ability of various
      experimental paradigms to demonstrate unambiguously such mentalizing. Evidence
      for implicit mentalizing has previously been provided by the 'dot perspective
      task,' where participants are slower to verify the number of dots they can see
      when an avatar can see a different number of dots. However, recent evidence
      challenged a mentalizing interpretation of this effect by showing it was
      unaltered when the avatar was replaced with an inanimate arrow stimulus. Here we
      present an extension of the dot perspective task using an invisibility cloaking
      device to render the dots invisible on certain trials. This paradigm is capable
      of providing unambiguous evidence of automatic mentalizing, but no such evidence
      was found. Two further well-powered experiments used opaque and transparent
      goggles to manipulate visibility but found no evidence of automatic mentalizing,
      nor of individual differences in empathy or perspective-taking predicting
      performance, contradicting previous studies using the same design. The results
      cast doubt on the existence of an implicit mentalizing system, suggesting that
      previous effects were due to domain-general processes. (PsycINFO Database Record

PMID- 27893271
TI  - Visual search for conjunctions of physical and numerical size shows that they are
      processed independently.
AB  - The size congruity effect refers to the interaction between numerical magnitude
      and physical digit size in a symbolic comparison task. Though this effect is well
      established in the typical 2-item scenario, the mechanisms at the root of the
      interference remain unclear. Two competing explanations have emerged in the
      literature: an early interaction model and a late interaction model. In the
      present study, we used visual conjunction search to test competing predictions
      from these 2 models. Participants searched for targets that were defined by a
      conjunction of physical and numerical size. Some distractors shared the target's
      physical size, and the remaining distractors shared the target's numerical size.
      We held the total number of search items fixed and manipulated the ratio of the 2
      distractor set sizes. The results from 3 experiments converge on the conclusion
      that numerical magnitude is not a guiding feature for visual search, and that
      physical and numerical magnitude are processed independently, which supports a
      late interaction model of the size congruity effect. (PsycINFO Database Record

PMID- 27893270
TI  - A link between attentional function, effective eye movements, and driving
      ability.
AB  - The misallocation of driver visual attention has been suggested as a major
      contributing factor to vehicle accidents. One possible reason is that the
      relatively high cognitive demands of driving limit the ability to efficiently
      allocate gaze. We present an experiment that explores the relationship between
      attentional function and visual performance when driving. Drivers performed 2
      variations of a multiple-object tracking task targeting aspects of cognition
      including sustained attention, dual-tasking, covert attention, and visuomotor
      skill. They also drove a number of courses in a driving simulator. Eye movements
      were recorded throughout. We found that individuals who performed better in the
      cognitive tasks exhibited more effective eye movement strategies when driving,
      such as scanning more of the road, and they also exhibited better driving
      performance. We discuss the potential link between an individual's attentional
      function, effective eye movements, and driving ability. We also discuss the use
      of a visuomotor task in assessing driving behavior. (PsycINFO Database Record

PMID- 27893272
TI  - Action effects are coded as transitions from current to future stimulation:
      Evidence from compatibility effects in tracking.
AB  - There is ample evidence that motor actions are stored in terms of, and controlled
      by, the sensory effects that these actions produce. At present it is unclear,
      though, whether action control is governed by intended sensory changes (e.g., the
      transition from darkness to brightness when switching on a light) or only by
      intended sensory end states (e.g., the light being on). The present study
      explored the role of sensory changes for action control. To address this issue,
      participants engaged in a spatial tracking task. We show that performance is
      determined by the compatibility between motor patterns and subsequent changes of
      a controlled stimulus, while the intended end state of the stimulus remains
      constant. Spatial compatibility increases performance even when perceptual
      changes of spatial features are not the primary target of control. These results
      suggest that intended transitions of stimulation have the potential to bias motor
      actions. We consider these results as an important step toward integrating closed
      loop regulation approaches and ideomotor approaches of action control. (PsycINFO
      Database Record

PMID- 27893273
TI  - Spontaneous rereading within sentences: Eye movement control and visual sampling.
AB  - Three experiments examine the role of previously read text in sentence
      comprehension and the control of eye movements during spontaneous rereading.
      Spontaneous rereading begins with a regressive saccade and involves reinspection
      of previously read text. All 3 experiments employed the gaze-contingent change
      technique to modulate the availability of previously read text. In Experiment 1,
      previously read text was permanently masked either immediately to the left of the
      fixated word (beyond wordn) or more than 1 word to the left (beyond wordn-1). The
      results of Experiment 1 indicate that the availability of the word immediately to
      the left (wordn-1) is important for comprehension. Experiments 2 and 3 further
      explored the role of previously read text beyond wordn-1. In these studies, text
      beyond wordn-1 was replaced, retaining only word length information, or word
      length and shape information. Following a regression back within a sentence,
      meaningful text either reappeared or remained unavailable during rereading. The
      experiments show that the visual format of text beyond wordn-1 (the parafoveal
      postview) is important for triggering regressions. The results also indicate
      that, as least for more complex sentences, the availability of meaningful text is
      important in driving eye movement control during rereading. (PsycINFO Database
      Record

PMID- 27893274
TI  - Perceptual adaptation of vowels generalizes across the phonology and does not
      require local context.
AB  - Listeners usually understand without difficulty even speech that sounds atypical.
      When they encounter noncanonical realizations of speech sounds, listeners can
      make short-term adjustments of their long-term representations of those sounds.
      Previous research, focusing mostly on adaptation in consonants, has suggested
      that for perceptual adaptation to take place some local cues (lexical,
      phonotactic, or visual) have to guide listeners' interpretation of the atypical
      sounds. In the present experiment we investigated perceptual adaptation in
      vowels. Our first aim was to show whether perceptual adaptation generalizes to
      unexposed but phonologically related vowels. To this end, we exposed Greek
      listeners to words or nonwords containing manipulated /i/ or /e/, and tested
      whether they adapted their perception of the /i/-/e/ contrast, as well as the
      unexposed /u/-/o/ contrast, which represents the same phonological height
      distinction. Our second aim was to test whether perceptual adaptation in vowels
      requires local context. Thus, a half of our listeners heard the manipulated
      vowels in real Greek words, while the other half heard them in nonwords providing
      no phonotactic cues on vowel identity. The results showed similar adjustment of
      /i/-/e/ categorization and of /u/-/o/ categorization, which indicates
      generalization of perceptual adaptation across phonologically related vowels.
      Furthermore, adaptation occurred irrespective of whether local context cues were
      present or not, suggesting that, at least in vowels, adaptation can be based on
      the distribution of auditory properties in the input. Our findings, confirming
      that fast perceptual adaptation in adult listeners occurs even for vowels,
      highlight the role of phonological abstraction in speech perception. (PsycINFO
      Database Record

PMID- 27893275
TI  - Re: "Identifying Underlying Emotional Instability and Utilizing a Combined
      Intervention in the Treatment of Childhood Constipation and Encopresis-A Case
      Report" by Jamie L. Davis (J Altern Complement Med 2016;22:489-492).

PMID- 27893276
TI  - Opportunities for HIV Prevention Communication During Sexual Encounters with
      Black Men Who Have Sex with Men.
AB  - Conversations about HIV prevention before engaging in sex may result in safer sex
      practices and decreased HIV transmission. However, partner communication for HIV
      prevention has been understudied among black/African American men who have sex
      with men (BMSM), a group that is disproportionately affected by HIV. We explored
      and described encounters and perceptions about HIV prevention conversations among
      BMSM and their sex partner(s) in New York City. We conducted an inductive
      thematic analysis of semi-structured interviews with BMSM who reported sex with a
      man in the previous 3 months. Interviews were professionally transcribed; Nvivo
      was used for data analysis. Twenty-two BMSM were included in this analysis;
      median age = 29.1 years; 71.4% self-identified as MSM; 85.7% were ever HIV
      tested; and 52.6% reported no disclosure or discussion about HIV status with
      their previous sex partner. The main themes were: (1) missed opportunities for
      HIV prevention conversations (e.g., no HIV prevention conversations or HIV
      prevention conversations after sex had occurred); (2) barriers to HIV prevention
      conversations (e.g., being in the moment; not wanting to pause); (3) emotional
      thoughts after sex (e.g., feeling worried about possible HIV exposure); and (4)
      rethinking relationships and sexual health (e.g., changed sex practices by asking
      partners' HIV status before sex; started using condoms). These findings offer
      insight into HIV prevention conversations by BMSM around the time of or during
      sexual encounters and may inform and strengthen partner-level HIV prevention
      communication interventions for BMSM.

PMID- 27893277
TI  - Lung Carcinoma Staging Update.
AB  - CONTEXT: - The International Association for the Study of Lung Cancer Staging
      Committee has prospectively created an international lung cancer database that
      was used to address many lung cancer staging questions, such as tumor size, nodal
      status, and metastatic disease. The proposed changes for the upcoming 8th edition
      of the cancer staging manual were based on survival data and better prognostic
      stratification of patients with lung cancer. OBJECTIVES: - To review published
      recommendations for the revision of lung carcinoma TNM staging and to address
      potential challenges in pathologic staging. DATA SOURCE: - PubMed available
      articles by the International Association for the Study of Lung Cancer Staging
      Committee were reviewed. CONCLUSIONS: - The TNM system remains the best
      prognosticator of lung cancer outcome. The recommendations are established on new
      prospective data analysis and reflect the improvements in prognostic separation
      of patients with lung cancer based on a multidisciplinary approach.

PMID- 27893278
TI  - Expected Fitness Gains of Randomized Search Heuristics for the Traveling
      Salesperson Problem.
AB  - Randomized search heuristics are frequently applied to NP-hard combinatorial
      optimization problems. The runtime analysis of randomized search heuristics has
      contributed tremendously to our theoretical understanding. Recently, randomized
      search heuristics have been examined regarding their achievable progress within a
      fixed-time budget. We follow this approach and present a fixed-budget analysis
      for an NP-hard combinatorial optimization problem. We consider the well-known
      Traveling Salesperson Problem (TSP) and analyze the fitness increase that
      randomized search heuristics are able to achieve within a given fixed-time
      budget. In particular, we analyze Manhattan and Euclidean TSP instances and
      Randomized Local Search (RLS), (1+1) EA and (1+[Formula: see text]) EA algorithms
      for the TSP in a smoothed complexity setting, and derive the lower bounds of the
      expected fitness gain for a specified number of generations.

PMID- 27893279
TI  - American Alcohol Photo Stimuli (AAPS): A standardized set of alcohol and matched
      non-alcohol images.
AB  - BACKGROUND: Photographic stimuli are commonly used to assess cue reactivity in
      the research and treatment of alcohol use disorder. The stimuli used are often
      non-standardized, not properly validated, and poorly controlled. There are no
      previously published, validated, American-relevant sets of alcohol images created
      in a standardized fashion. OBJECTIVES: We aimed to: 1) make available a
      standardized, matched set of photographic alcohol and non-alcohol beverage
      stimuli, 2) establish face validity, the extent to which the stimuli are
      subjectively viewed as what they are purported to be, and 3) establish construct
      validity, the degree to which a test measures what it claims to be measuring.
      METHODS: We produced a standardized set of 36 images consisting of American
      alcohol and non-alcohol beverages matched for basic color, form, and complexity.
      A total of 178 participants (95 male, 82 female, 1 genderqueer) rated each image
      for appetitiveness. An arrow-probe task, in which matched pairs were categorized
      after being presented for 200 ms, assessed face validity. Criteria for construct
      validity were met if variation in AUDIT scores were associated with variation in
      performance on tasks during alcohol image presentation. RESULTS: Overall, images
      were categorized with >90% accuracy. Participants' AUDIT scores correlated
      significantly with alcohol "want" and "like" ratings [r(176) = 0.27, p = <0.001;
      r(176) = 0.36, p = <0.001] and arrow-probe latency [r(176) = -0.22, p = 0.004],
      but not with non-alcohol outcomes. Furthermore, appetitive ratings and arrow
      probe latency for alcohol, but not non-alcohol, differed significantly for heavy
      versus light drinkers. CONCLUSION: Our image set provides valid and reliable
      alcohol stimuli for both explicit and implicit tests of cue reactivity. The use
      of standardized, validated, reliable image sets may improve consistency across
      research and treatment paradigms.

PMID- 27893280
TI  - Establishment of a Human Breast Cancer Model by Fusion PCR for In Vivo and In
      Vitro Fluorescence Imaging of Human Breast Cancer.
AB  - This study aimed to construct a breast cancer model that could continuously
      express the genes of luciferase and green fluorescent protein. The genes
      luciferase, EGFP, and Neo were obtained by fusion polymerase chain reaction (PCR)
      and inserted into pAAV-MCS. The pAAV-Luciferase-EGFP-Neo vector was transfected
      into MDA-MB-231 cells. After antibiotic resistance gene screening and limiting
      dilution assay, we constructed a monoclonal stable cell line that expresses the
      fusion protein Luciferase-EGFP. In comparison with the polyclonal stable cell
      line, the monoclonal cell line had good genetic stability and was not different
      from the parental cell line MDA-MB-231. The monoclonal stable cell line would be
      ideal for a breast cancer model. Indices of fluorescence imaging can be applied
      to fluorescence imaging in vitro and in vivo, providing a straightforward and
      reliable system for breast cancer and drug discovery research.

PMID- 27893281
TI  - The effects of drug and alcohol consumption on driver injury severities in single
      vehicle crashes.
AB  - OBJECTIVE: It is well known that alcohol and drugs influence driving behavior by
      affecting the central nervous system, awareness, vision, and perception/reaction
      times, but the resulting effect on driver injuries in car crashes is not fully
      understood. The purpose of this study was to identify factors affecting the
      injury severities of unimpaired, alcohol-impaired, and drug-impaired drivers.
      METHOD: The current article applies a random parameters logit model to study the
      differences in injury severities among unimpaired, alcohol-impaired, and drug
      impaired drivers. Using data from single-vehicle crashes in Cook County,
      Illinois, over a 9-year period from January 1, 2004, to December 31, 2012,
      separate models for unimpaired, alcohol-impaired, and drug-impaired drivers were
      estimated. A wide range of variables potentially affecting driver injury severity
      was considered, including roadway and environmental conditions, driver
      attributes, time and location of the crash, and crash-specific factors. RESULTS:
      The estimation results show significant differences in the determinants of driver
      injury severities across groups of unimpaired, alcohol-impaired, and drug
      impaired drivers. The findings also show that unimpaired drivers are
      understandably more responsive to variations in lighting, adverse weather, and
      road conditions, but these drivers also tend to have much more heterogeneity in
      their behavioral responses to these conditions, relative to impaired drivers. In
      addition, age and gender were found to be important determinants of injury
      severity, but the effects varied significantly across all drivers, particularly
      among alcohol-impaired drivers. CONCLUSIONS: The model estimation results show
      that statistically significant differences exist in driver injury severities
      among the unimpaired, alcohol-impaired, and drug-impaired driver groups
      considered. Specifically, we find that unimpaired drivers tend to have more
      heterogeneity in their injury outcomes in the presence potentially adverse
      weather and road surface conditions. This makes sense because one would expect
      unimpaired drivers to apply their full knowledge/judgment range to deal with
      these conditions, and the variability of this range across the driver population
      (with different driving experiences, etc.) should be great. In contrast, we find,
      for the most part, that alcohol-impaired and drug-impaired drivers have far less
      heterogeneity in the factors that affect injury severity, suggesting an
      equalizing effect resulting from the decision-impairing substance.

PMID- 27893282
TI  - Plant Food Supplements with Antioxidant Properties for the Treatment of Chronic
      and Neurodegenerative Diseases: Benefits or Risks?
AB  - Wine by-products, in particular grape pomace, can be an important source of
      polyphenols and dietary fibers and are increasingly being used as a starting
      material in the industrial production of plant food supplements, such as other
      matrices containing biomolecules, with antioxidant properties. The risk
      associated with the consumption of these products was recently analyzed through a
      study of potential genotoxic and carcinogenic compounds that can be found in the
      marketed products. In particular, occurrence data about contamination with the
      mycotoxin ochratoxin A were also reported. This short review aims at giving an
      overview about the quality and benefits of these kinds of food supplements, and
      also about risks of incorrect use, focusing on the emerging need for stricter
      European regulations.

PMID- 27893283
TI  - Driver speed selection on high-speed two-lane highways: Comparing speed profiles
      between uniform and differential speed limits.
AB  - OBJECTIVE: Although a considerable amount of prior research has investigated the
      impacts of speed limits on traffic safety and operations, much of this research,
      and nearly all of the research related to differential speed limits, has been
      specific to limited access freeways. The unique safety and operational issues on
      highways without access control create difficulty relating the conclusions from
      prior freeway-related speed limit research to 2-lane highways, particularly
      research on differential limits due to passing limitations and subsequent
      queuing. Therefore, the objective of this study was to assess differences in
      driver speed selection with respect to the posted speed limit on rural 2-lane
      highways, with a particular emphasis on the differences between uniform and
      differential speed limits. METHODS: Data were collected from nearly 59,000
      vehicles across 320 sites in Montana and 4 neighboring states. Differences in
      mean speeds, 85th percentile speeds, and the standard deviation in speeds for
      free-flowing vehicles were examined across these sites using ordinary least
      squares regression models. RESULTS: Ultimately, the results of the analysis show
      that the mean speed, 85th percentile speed, and variability in travel speeds for
      free-flowing vehicles on 2-lane highways are generally lower at locations with
      uniform 65 mph speed limits, compared to locations with differential limits of 70
      mph for cars and 60 mph for trucks. CONCLUSIONS: In addition to posted speed
      limits, several site characteristics were shown to influence speed selection
      including shoulder widths, frequency of horizontal curves, percentage of the
      segment that included no passing zones, and hourly volumes. Differences in
      vehicle speed characteristics were also observed between states, indicating that
      speed selection may also be influenced by local factors, such as driver
      population or enforcement.

PMID- 27893284
TI  - Biomarkers and Metabolic Patterns in the Sediments of Evolving Glacial Lakes as a
      Proxy for Planetary Lake Exploration.
AB  - Oligotrophic glacial lakes in the Andes Mountains serve as models to study the
      effects of climate change on natural biological systems. The persistent high UV
      regime and evolution of the lake biota due to deglaciation make Andean lake
      ecosystems potential analogues in the search for life on other planetary bodies.
      Our objective was to identify microbial biomarkers and metabolic patterns that
      represent time points in the evolutionary history of Andean glacial lakes, as
      these may be used in long-term studies as microscale indicators of climate change
      processes. We investigated a variety of microbial markers in shallow sediments
      from Laguna Negra and Lo Encanado lakes (Region Metropolitana, Chile). An on-site
      immunoassay-based Life Detector Chip (LDChip) revealed the presence of sulfate
      reducing bacteria, methanogenic archaea, and exopolymeric substances from
      Gammaproteobacteria. Bacterial and archaeal 16S rRNA gene sequences obtained from
      field samples confirmed the results from the immunoassays and also revealed the
      presence of Alpha-, Beta-, Gamma-, and Deltaproteobacteria, as well as
      cyanobacteria and methanogenic archaea. The complementary immunoassay and
      phylogenetic results indicate a rich microbial diversity with active sulfate
      reduction and methanogenic activities along the shoreline and in shallow
      sediments. Sulfate inputs from the surrounding volcanic terrains during
      deglaciation may explain the observed microbial biomarker and metabolic patterns,
      which differ with depth and between the two lakes. A switch from aerobic and
      heterotrophic metabolisms to anaerobic ones such as sulfate reduction and
      methanogenesis in the shallow shores likely reflects the natural evolution of the
      lake sediments due to deglaciation. Hydrodynamic deposition of sediments creates
      compartmentalization (e.g., sediments with different structure and composition
      surrounded by oligotrophic water) that favors metabolic transitions. Similar
      phenomena would be expected to occur on other planetary lakes, such as those of
      Titan, where watery niches fed by depositional events would be surrounded by a
      "sea" of hydrocarbons. Key Words: Glacier lakes-Sedimentation-Prokaryotic
      metabolisms and biomarkers-Deglaciation-Life detection-Planetary exploration.
      Astrobiology 18, 586-606.

PMID- 27893285
TI  - Recent advances in subtyping tumors of the central nervous system using molecular
      data.
AB  - INTRODUCTION: Primary brain tumors account for substantial morbidity and
      mortality. They often infiltrate the brain diffusely, continue growing, and cause
      adverse events, such as headaches, seizures, and neurological deficits. The
      classification of primary brain tumors, based for decades on histology, has been
      fundamentally changed by the World Health Organization in 2016 by incorporation
      of molecular data. Areas covered: Literature from glioblastomas, high- and low
      grade astrocytic, oligodendroglial, glioneuronal and ependymal tumors from the
      last five years were reviewed. Results from comprehensive molecular profiling of
      neoplasms and impact of recent molecular subtyping on neuropathological diagnosis
      are presented. Expert commentary: The identification of frequent acquired
      mutations shows that adult and pediatric glioblastomas have divergent biology
      with differing prognoses. Astrocytoma and oligodendroglioma are more closely
      related than previously thought. Molecular profiling now enables the precise
      classification of most diffuse gliomas into three clinically and therapeutically
      different subtypes according to the presence or absence of IDH mutation and
      1p/19q codeletion. New subgroups with different clinical outcomes and anatomic
      locations have emerged in ependymomas and pediatric embryonal tumors.

PMID- 27893286
TI  - Cessation of Nocturnal Enuresis with Aripiprazole.

PMID- 27893288
TI  - Analyzing injury severity of bus passengers with different movements.
AB  - OBJECTIVE: Though public transport vehicles are rarely involved in mass casualty
      accidents, when they are, the number of injuries and fatalities is usually high
      due to the high passenger capacity. Of the few studies that have been conducted
      on bus safety, the majority focused on vehicle safety features, road
      environmental factors, as well as driver characteristics. Nevertheless, few
      studies have attempted to investigate the underlying risk factors related to bus
      occupants. This article presents an investigation aimed at identifying the risk
      factors affecting injury severity of bus passengers with different movements.
      METHOD: Three different passenger movement types including standing, seated, and
      boarding/alighting were analyzed individually using classification and regression
      tree (CART) method based on publicly available accident database of Great
      Britain. RESULTS: According to the results of exploratory analyses, passenger age
      and vehicle maneuver are associated with passenger injury severity in all 3 types
      of accidents. Moreover, the variable "skidding and overturning" is associated
      with injury severity of seated passengers and driver age is correlated with
      injury severity of standing and boarding/alighting passengers. CONCLUSIONS: The
      CART method shows its ability to identify and easily explain the complicated
      patterns affecting passenger injury severity. Several countermeasures to reduce
      bus passenger injury severity are recommended.

PMID- 27893287
TI  - Hepatitis E Virus in Wild Boar in Northwest Poland: Sensitivity of Methods of
      Detection.
AB  - In northwest Poland, 163 blood and 53 fecal samples of wild boars were collected
      in winter 2012/13 and 2013/14. All blood samples were tested for the presence of
      hepatitis E virus (HEV) ribonucleic acid (RNA) by two reverse transcription
      polymerase chain reaction (RT-PCR) based methods and by anti-HEV IgG enzyme
      linked immunosorbent assay (ELISA). About 17.2% of blood samples were
      seropositive. One-step nested RT-PCR turned out to be too insensitive (11.6% were
      positive). Therefore a two-step nested RT-PCR was applied where 25.8% of the
      blood samples were tested positive for HEV RNA. About 50.0% of blood samples
      positive in ELISA were also positive in two-step nested RT-PCR. The prevalence of
      HEV RNA in feces was 9.4%. Based on the results of blood (ELISA, PCR) and fecal
      (PCR) tests, the overall prevalence of HEV in wild boars in northwest Poland was
      36.8%. There was no correlation between the ELISA results and the presence of HEV
      RNA in plasma or in feces. According to the sequencing results of 348 bp PCR
      products of HEV, there were four different subtypes identified. Reports on the
      prevalence of HEV in wild boar populations are varying due to different
      sensitivities of the detection methods. However, this study reveals based on a
      highly sensitive method that HEV is widely spread in wild boar populations in the
      northwestern region of Poland and posing a potential risk to the consumer of game
      meat.

PMID- 27893289
TI  - Solitary Active Videogame Play Improves Executive Functioning More Than
      Collaborative Play for Children with Special Needs.
AB  - OBJECTIVE: This pilot study examined the impact of playing an active videogame on
      executive functioning (EF) skills for children with special needs, who typically
      have lower EF skills. MATERIALS AND METHODS: Acute EF change was measured in 36
      children with a range of special needs, including mental health disorders and
      developmental disabilities. Participants were assigned to one of two active
      videogame conditions: playing alone and playing with a peer. Two different EF
      tasks were conducted pre- and postplay. RESULTS: Children who played alone
      increased their accuracy performance more than children in the paired-play
      condition on two measures of EF. The study explored potential covariates of prior
      videogame experience, age, and enjoyment, but none of these variables related to
      EF change. CONCLUSION: This study's findings support active videogame play as an
      activity that can boost EF skills for children with special needs when they play
      alone. Future research should continue to examine the relationships between EF
      and active videogame play with a peer to elucidate the contributions of social
      interactions.

PMID- 27893290
TI  - Gene alterations and epigenetic changes in intrahepatic cholangiocarcinoma.
AB  - INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant
      neoplasm. The incidence of ICC has been increasing world-wide over the past
      several decades. Areas covered: The pathogenesis of ICC is a complex process
      involving the alteration of specific genes and epigenetic changes. This review
      summarizes the advances in research of gene alterations and epigenetic changes in
      ICC; it also aims to promote the findings of new biomarkers that can be used to
      diagnose ICC and to provide novel ideas for the combination of molecular targeted
      therapies. Expert commentary: Surgical resection is regarded as the most
      effective curative treatment, although in many cases, resectability and
      curability are unsatisfactory. Furthermore, many patients are diagnosed at
      advanced stages and have to resort to chemotherapy, which is rarely curative.
      Many of the molecular mechanisms of ICC are yet to be determined; once these
      determinations are made, then ICC may be able to be treated by precise targeted
      drugs.

PMID- 27893291
TI  - Association between use of short-acting benzodiazepines and migraine occurrence:
      a nationwide population-based case-control study.
AB  - AIM: To evaluate the association between using benzodiazepines (BZDs) with short-
      or long-acting durations and migraine occurrence. METHODS: The migraine group
      comprised 9616 subjects older than 20 years and newly diagnosed with migraine
      between 2005 and 2011, and the comparison group comprised 38,464 subjects without
      migraine. The BZDs used in the subjects were dichotomously defined as short
      acting (half-life <=24 h) and long-acting substances. A logistic regression model
      was used to calculate the odds ratio (OR) of migraine associated with BZD
      exposure and other diseases. RESULTS: The adjusted OR of migraine associated with
      BZD exposure was 1.73 (95% confidence interval [CI] = 1.63-1.84). Either exposure
      to a short-acting BZD alone or using it combining with a long-acting BZD had
      significant higher risks of migraine (adjusted OR = 1.69, 95% CI = 1.59-1.80;
      adjusted OR = 2.06, 95% CI = 1.91-2.24, respectively), whereas only long-acting
      BZD use was not associated with an increase of migraine. Meanwhile, sleep
      disorders, anxiety, and stroke were strongly associated with migraine (adjusted
      OR = 2.00, 1.91, and 1.57, respectively). CONCLUSIONS: We observed a significant
      increase of migraine occurrence in subjects using short-acting BZDs, either alone
      or in combination with long-acting ones.

PMID- 27893292
TI  - INAPPROPRIATE USE OF SUPPRESSIVE DOSES OF THYROID HORMONE IN THYROID NODULE
      MANAGEMENT: RESULTS FROM A NATIONWIDE SURVEY.

PMID- 27893294
TI  - Management of Multifactorial Infant Delirium with Intravenous Haloperidol in the
      Setting of Over Sedation and Poor Enteral Absorption.

PMID- 27893295
TI  - Medical Directors of Breastfeeding Programs at Academic Medical Centers: Duties
      and Challenges.
AB  - INTRODUCTION: An emerging trend in Academic Medical Centers (AMCs) is to
      coordinate breastfeeding care, research, and trainee education through "medical
      director" positions. Little is known about their duties, supports, and
      challenges. OBJECTIVE: To determine the duties and challenges of directors of
      breastfeeding medicine in AMCs. METHODS: A survey was distributed four times over
      a 3-month period to three listservs with a total of 860 members. Physicians
      directing breastfeeding programs or services at AMCs were included. Participants
      were asked about details of their employment, time distribution of the position,
      their role in education, billing practices, and major hurdles. RESULTS: Thirty
      two physicians responded to the survey: 25 from the United States, and seven
      international. Only 22% of respondents had formal job descriptions and only 31%
      reported being paid for their breastfeeding work. Most positions were created in
      the past 10 years (75%), were housed in Departments of Pediatrics (75%), and
      provided clinical services for breastfeeding in inpatient and outpatient
      settings. Ninety-one percent of respondents educated trainees and provided
      oversight of lactation consultants. Major hurdles included difficulties with
      billing for services, lack of protected time and personal reimbursement, lack of
      formal structure and job descriptions, and lack of buy-in at the institutional
      and sometimes governmental levels. CONCLUSIONS: Medical Directors of
      Breastfeeding Services may be increasingly prevalent in AMCs and are engaged in
      inpatient and outpatient clinical work, trainee education, and lactation
      consultant oversight. Both financial and structural hurdles were reported by
      those holding these positions.

PMID- 27893293
TI  - PREVELENCE OF PRIMARY ALDOSTERONISM IN AN URBAN HYPERTENSIVE POPULATION.
AB  - OBJECTIVE: To determine the prevalence of primary aldosteronism (PA) in
      hypertensive patients presenting to the primary care clinic at The Mount Sinai
      Hospital, regardless of the degree of hypertension and to identify clinical
      criteria that should prompt screening for PA. METHODS: An aldosterone:renin ratio
      (ARR, cutoff >=20, with plasma aldosterone concentration [PAC] >=10 and
      suppressed renin) was used to prospectively screen 296 hypertensive patients
      (blood pressure [BP] >=140/90) over the age of 18 from August 2012 through May
      2013. Subjects who screened positive then underwent confirmatory oral salt load
      testing (OSLT). RESULTS: Of the 296 patients, 14 screened positive for PA, an
      overall prevalence of 4.7%. Six of the 14 cases underwent confirmatory OSLT, upon
      which 2 were confirmed positive, for a prevalence of 0.7%. Overall, patients with
      confirmed PA were more likely to have resistant hypertension (42.9% vs. 18.1% (P
      = .0334)) and require more antihypertensive agents (2.8 +/- 1.2 agents vs. 2.1 +/
      1.1 agents, P = .0213). There was a trend toward lower potassium values in the
      cases. CONCLUSION: The prevalence of PA in our clinic is much lower than in
      reports from certain "at-risk" populations. PA screening is indicated in patients
      with resistant hypertension, regardless of serum potassium levels. ABBREVIATIONS:
      ARR = aldosterone:renin ratio ACTH = adrenocorticotropic hormone AVS = adrenal
      venous sampling BP = blood pressure MRA = mineralocorticoid receptor antagonist
      OSLT = oral salt load confirmatory test PA = primary aldosteronism PAC = plasma
      aldosterone concentration PCP = primary care provider PRA = plasma renin
      activity.

PMID- 27893296
TI  - Evaluation of Visual Field Test Parameters after Artificial Tear Administration
      in Patients with Glaucoma and Dry Eye.
AB  - PURPOSE: To examine the effect of a single dose of artificial tear administration
      on automated visual field (VF) testing in patients with glaucoma and dry eye
      syndrome. MATERIAL AND METHODS: A total of 35 patients with primary open-angle
      glaucoma experienced in VF testing with symptoms of dry eye were enrolled in this
      study. At the first visit, standard VF testing was performed. At the second and
      third visits with an interval of one week, while the left eyes served as control,
      one drop of artificial tear was administered to each patient's right eye, and
      then VF testing was performed again. The reliability parameters, VF indices,
      number of depressed points at probability levels of pattern deviation plots, and
      test times were compared between visits. RESULTS: No significant difference was
      observed in any VF testing parameters of control eyes (P>0.05). In artificial
      tear administered eyes, significant improvement was observed in test duration,
      mean deviation, and the number of depressed points at probability levels (P?0.5%,
      P?1%, P?2) of pattern deviation plots (P?0.05). The post-hoc test revealed that
      artificial tear administration elicited an improvement in test duration, mean
      deviation, and the number of depressed points at probability levels (P?0.5%,
      P?1%, P?2%) of pattern deviation plots from first visit to second and third
      visits (P?0.01, for all comparisons). The intraclass correlation coefficient for
      the three VF test indices was found to be between 0.735 and 0.85 (P<0.001, for
      all). DISCUSSION: A single dose of artificial tear administration immediately
      before VF testing seems to improve test results and decrease test time.

PMID- 27893297
TI  - Population-Based Trachoma Mapping in Six Evaluation Units of Papua New Guinea.
AB  - PURPOSE: We sought to determine the prevalence of trachomatous inflammation -
      follicular (TF) in children aged 1-9 years, and trachomatous trichiasis (TT) in
      those aged >=15 years, in suspected trachoma-endemic areas of Papua New Guinea
      (PNG). METHODS: We carried out six population-based prevalence surveys using the
      protocol developed as part of the Global Trachoma Mapping Project. RESULTS: A
      total of 19,013 individuals were sampled for inclusion, with 15,641 (82.3%)
      consenting to participate. Four evaluation units had prevalences of TF in
      children >=10%, above which threshold the World Health Organization (WHO)
      recommends mass drug administration (MDA) of azithromycin for at least three
      years; Western Province (South Fly/Daru) 11.2% (95% confidence interval, CI, 6.9
      17.0%), Southern Highlands (East) 12.2% (95% CI 9.6-15.0%), Southern Highlands
      (West) 11.7% (95% CI 8.5-15.3%), and West New Britain 11.4% (95% CI 8.7-13.9%).
      TF prevalence was 5.0-9.9% in Madang (9.4%, 95% CI 6.1-13.0%) and National
      Capital District (6.0%. 95% CI 3.2-9.1%) where consideration of a single round of
      MDA is warranted. Cases of TT were not found outside West New Britain, in which
      four cases were seen, generating an estimated population-level prevalence of TT
      in adults of 0.10% (95% CI 0.00-0.40%) for West New Britain, below the WHO
      elimination threshold of 0.2% of those aged >=15 years. CONCLUSION: Trachoma is a
      public health issue in PNG. However, other than in West New Britain, there are
      few data to support the idea that trachoma is a cause of blindness in PNG.
      Further research is needed to understand the stimulus for the active trachoma
      phenotype in these populations.

PMID- 27893298
TI  - Replication, checkpoint suppression and structure of centromeric DNA.
AB  - Human centromeres contain large amounts of repetitive DNA sequences known as
      alpha satellite DNA, which can be difficult to replicate and whose functional
      role is unclear. Recently, we have characterized protein composition, structural
      organization and checkpoint response to stalled replication forks of centromeric
      chromatin reconstituted in Xenopus laevis egg extract. We showed that centromeric
      DNA has high affinity for SMC2-4 subunits of condensins and for CENP-A, it is
      enriched for DNA repair factors and suppresses the ATR checkpoint to ensure its
      efficient replication. We also showed that centromeric chromatin forms condensins
      enriched and topologically constrained DNA loops, which likely contribute to the
      overall structure of the centromere. These findings have important implications
      on how chromosomes are organized and genome stability is maintained in mammalian
      cells.

PMID- 27893299
TI  - Does apoptotic activity have a role in the development of the placental
      abruption?
AB  - OBJECTIVE: The purpose of the present study is to analyses the role of apoptotic
      activity in placental abruption (PA) development by evaluating the level of
      plasma M30-M65. METHODS: The study group included 46 pregnant women who underwent
      caesarean sections (CS) because of PA, and the control group included 48 pregnant
      women who underwent CS because of obstetric causes. Venous blood samples were
      received from all expectants before starting the CS for the purpose of evaluating
      the M30-M65 levels, which are indicators of apoptotic activity in maternal
      plasma. RESULTS: The plasma M30-M65 levels were determined to be statistically
      significantly higher in with PA group. The sensitivity and specificity of the
      test were determined to be 71.7% and 64.6%, respectively in identifying the
      expectants with PA when the cut-off value was taken as 163.50 U/L for the plasma
      M30 value. The sensitivity and specificity of the test were determined to be
      76.1% and 66.7%, respectively in identifying the PA when the cut-off value was
      taken as 295.50 U/L for the M65 value. CONCLUSIONS: The increase of apoptotic
      activity induced by thrombin resulting from decidual bleeding may have a role in
      the development of PA.

PMID- 27893302
TI  - Letter to the Editor Regarding Wiesel et al.: Minimally Invasive Esophagectomy.

PMID- 27893300
TI  - The Use of Robotic and Laparoscopic Surgical Stapling Devices During Minimally
      Invasive Colon and Rectal Surgery: A Comparison.
AB  - PURPOSE: To date there exists no published study examining the safety and
      efficacy of the EndoWrist 45 (Intuitive Surgical, Inc.) robotic stapler. We
      compared outcomes between the robotic and comparable laparoscopic stapler in
      robotic-assisted colorectal procedures. MATERIALS AND METHODS: We conducted a
      retrospective review of 93 patients who underwent robotic-assisted colorectal
      surgery at our institution from 2012 to 2014. Surgeries included left, sigmoid,
      subtotal and total colectomies, and low anterior rectal resections. Indications
      were malignancy and diverticular and inflammatory bowel disease. Preoperative
      demographics, intraoperative data, and postoperative outcomes were examined.
      Student's t-test and Fischer's exact used were appropriate. RESULTS: Forty-five
      millimeters laparoscopic staplers were used in 58 cases, while the 45 mm robotic
      stapler was used in 35 cases. There was no difference in age (P = .651), gender
      (P = .832), or body mass index (P = .204) between groups. There was no difference
      in estimated blood loss (P = .524), operative time (P = .769), length of stay (P
      = .895), or complication rate (P = .778). The robotic stapler group had one
      anastomotic leak, while the laparoscopic stapler group had six (P = .705). There
      were more laparoscopic stapler fires (2.69) per patient than robotic stapler
      fires (1.86) (P = .001). The cost per patient for the laparoscopic group was
      $631.45 versus $473.28 for the robotic group (P = .001). CONCLUSION: This is the
      first study to evaluate the robotic stapler. Advantages of the robotic stapler
      include large range of motion and 90 degrees  of articulation, which may provide
      a benefit when using the stapler in difficult areas like the pelvis. The robotic
      stapler has a comparable level of safety as a 45 mm laparoscopic stapler and is
      more cost effective.

PMID- 27893301
TI  - Optimizing the expression of a Heterologous chitinase: A study of different
      promoters.
AB  - Many relevant applications have been demonstrated for chitinolytic enzymes.
      However, their successful exploitation depends upon the availability of strains
      and expression conditions that allow the production of active forms and large
      quantities of these enzymes. Escherichia coli has been commonly used to express
      and overproduce different proteins, among them chitinases. Improving the
      functional gene expression of chitinases is key to exploiting their potential. In
      a recent study, we described the effect of various parameters on the functional
      expression of 2 chitinases from different families, demonstrating that the effect
      of each of these parameters on the activity of both chitinases was specific to
      each enzyme. In this study, the expression of a Lactococcus lactis chitinase
      encoded by a new allele, ChiA1-2, was optimized. The results showed that not only
      the expression parameters seemed to influence protein production, solubility and
      activity but also the plasmid used for the expression. Herein, we describe the
      effect of 2 different promoters, tac and T7, on the expression of the active form
      of the chitinolytic enzyme.

PMID- 27893304
TI  - Blame it on Southern, but it's a western blot.
AB  - Edwin M. Southern is a professor emeritus at the University of Oxford. He is
      perhaps best known for development of the "Southern blot" (Dr. Southern was at
      the University of Edinburgh when he wrote his landmark paper). The Southern blot
      provided a scientific breakthrough by allowing scientists to detect a particular
      DNA sequence without first purifying it from the rest of the genome; the basic
      method involves the transfer of the DNA to a membrane, followed by detection with
      a specific probe. Although few people perform Southern blots as originally
      carried out by Southern, due in part to the more recent technique of the
      polymerase chain reaction, the basic concept continues to play an important role
      in molecular biology.

PMID- 27893305
TI  - Foreword: Special focus issue on semaphorins.

PMID- 27893303
TI  - Do Patient Characteristics Decide if Young Adult Cancer Patients Undergo
      Fertility Preservation?
AB  - PURPOSE: The Fertility Attitudes and Cancer Treatment Study (FACTS) is a two
      phase research initiative aimed to understand factors involved with decision
      making for future fertility. The FACTS will improve services and utilization of
      fertility preservation (FP) before cancer treatment. Phase-I examined patient
      characteristics as associated with FP decision. METHODS: A retrospective cohort
      study of 108 reproductive-aged (18-45 years) males and females who received a
      fertility consultation before cancer treatment from January 1, 2012 to April 30,
      2014 was conducted. Chi-square, student's t-test, and logistic regression were
      conducted to examine associations with FP decision. RESULTS: The utilization rate
      of FP following fertility consultation was 49%. Gender was the most significant
      factor contributing to FP decision; 74% of those who choose FP were male (odds
      ratio = 12.5; 95% confidence interval 5.1-31.4). Those who opted for FP were more
      likely to be Caucasian (p = 0.042), have a solid tumor (p = 0.03), and have a
      shorter time from diagnosis to fertility consultation (29.5 vs. 58.8 days; p =
      0.017). Age, relationship, tumor location, treatment plan, and parity were not
      significant predictors of FP. CONCLUSIONS: Current perceptions about patient
      demographics do not predict FP utilization by young adult cancer patients.
      Providing patients an informed fertility consultation has demonstrated an
      increase in FP utilization to nearly one-half of patients. Despite gender being a
      significant factor in choosing FP, the study did not provide reasons as to why.
      The phase-II study will explore patients' reasons for FP decision in a
      qualitative design to understand these differences.

PMID- 27893307
TI  - Barriers to Increasing Physical Activity Among Young Adult Cancer Survivors.
AB  - Increasing physical activity may reduce some of the physical and mental health
      risks faced by young adult cancer survivors. Unfortunately, most young survivors
      are sedentary. The aim of this study was to identify barriers experienced by
      young survivors attempting to increase their physical activity; a better
      understanding of these barriers may yield more efficacious interventions for this
      population. Data on physical activity barriers were collected during an
      intervention for 18-to-39-year-old survivors. Findings indicated that
      participants faced a variety of barriers, including limited time and health
      related issues. An exploratory analysis suggested that health-related barriers
      may impact postintervention levels of physical activity.

PMID- 27893306
TI  - Mesh Fixation with Fibrin Sealant in Totally Extraperitoneal Hernia Repair.
AB  - INTRODUCTION: Repair of inguinal hernia is a common procedure, but there is a
      lack of consensus as to the optimal repair technique along with the use of mesh
      and methods of mesh fixation. The objective of this study was to evaluate the
      efficacy and safety of fibrin sealant for mesh fixation in laparoscopic totally
      extraperitoneal (TEP) inguinal hernia repair. MATERIALS AND METHODS: A study was
      conducted of the first 200 patients undergoing TEP hernia repair with mesh
      fixation using fibrin sealant between March 2012 and January 2014. The primary
      outcome measures were (1) chronic pain (persisting for >3 months), (2)
      persistence of hernia (recurrence identified within first 2 weeks
      postoperatively), (3) hernia recurrence, and (4) any additional perioperative
      complications. The mean follow-up in the series was 34.4 +/- 6.1 months (range
      22.2-44.1). RESULTS: Of the 278 hernias repaired in 204 patients (74 bilateral,
      130 unilateral), 38 were recurrent and 240 were primary. Three patients (1.5%)
      had a persistent hernia, including one with a planned return to the operating
      room the next day due to poor visualization. Three patients (1.5%) had a hernia
      recurrence. Twelve patients (5.9%) reported experiencing chronic pain. The
      remaining complications were minor and resolved over time. CONCLUSIONS: TEP
      repair of inguinal hernia using mesh secured with fibrin sealant can be
      effectively used to treat primary, recurrent, unilateral, and bilateral inguinal
      hernias in adults with minimal recurrence rates and complications during almost 3
      years of follow-up.

PMID- 27893308
TI  - Evaluation of Hypotensive and Antihypertensive Effects of Velvet Bean (Mucuna
      pruriens L.) Hydrolysates.
AB  - Hypertension could cause significant worldwide health problems that affect 15-20%
      of all adults; according to National Health and Nutrition Examination Survey,
      about 29% of the adult population in the United States are hypertensive. Recent
      research has shown that peptides derived from the hydrolysis of food proteins can
      decrease blood pressure. This study was carried out to evaluate the hypotensive
      and antihypertensive potential of Mucuna pruriens protein hydrolysates in in
      vitro and in vivo models. M. pruriens protein concentrate was prepared by wet
      fractionation and enzymatically hydrolyzed using Alcalase(r), Flavourzyme(r), and
      the sequential system Alcalase-Flavourzyme at different times (5-120 min). The
      biological potential was measured in vitro based on the IC50 value as well as in
      vivo effect, measuring the systolic (SBP) and diastolic (DBP) blood pressure in
      normotensive and antihypertensive Wistar-Kyoto rats by the tail-cuff method.
      Hydrolysis of M. pruriens protein concentrates with commercial enzymes generated
      extensive hydrolysates with angiotensin-converting enzyme (ACE-I) inhibitory
      activity (IC50: 0.589-0.993 mg/mL) and hypotensive (SBP: 0.6-47.43%, DBP: 1.94
      43.47%) and antihypertensive (SBP: 8.84-27.29% DBP: 16.1-29.37%) effect. These
      results indicate that Mucuna pruriens protein hydrolysate (MPPH) could be used as
      a functional ingredient to prevent blood pressure increase.

PMID- 27893309
TI  - Acarological Risk of Borrelia burgdorferi Sensu Lato Infections Across Space and
      Time in The Netherlands.
AB  - A longitudinal investigation on tick populations and their Borrelia infections in
      the Netherlands was undertaken between 2006 and 2011 with the aim to assess
      spatial and temporal patterns of the acarological risk in forested sites across
      the country and to assess variations in Borrelia genospecies diversity. Ticks
      were collected monthly in 11 sites and nymphs were examined for Borrelia
      infections. Tick populations expressed strong seasonal variations, with
      consistent and significant differences in mean tick densities between sites.
      Borrelia infections were present in all study sites, with a site-specific mean
      prevalence per month ranging from 7% to 26%. Prevalence was location-dependent
      and was not associated with tick densities. Mean Borrelia prevalence was lowest
      in January (4%), gradually increasing to reach a maximum (24%) in August.
      Borrelia afzelii represented 70% of all infections, with Borrelia burgdorferi
      sensu stricto, Borrelia garinii, and Borrelia valaisiana represented with 4%, 8%,
      and 10%, respectively. The density of infected nymphs and the proportional
      distribution of the four Borrelia genospecies, were significantly different
      between sites. The results show a consistent and significant spatial and temporal
      difference in acarological risk across the Netherlands.

PMID- 27893310
TI  - Participation and Intellectual Disability: A Review of the Literature.
AB  - Participation is a central aspect of human functioning and a key focus of
      research and practice in the intellectual disability field. However, there is not
      an accepted definition of participation that guides research and practice. To
      inform the development of a definition, a scoping review of the intellectual
      disability literature from 2001-2015 was conducted. Findings suggest that
      existing research rarely uses definitions of participation, but does examine
      participation across multiple domains and addresses issues of access and
      inclusion. Less focus was placed on individual aspects of participation such as
      meaning, responsibility, and choice. Based on the findings, implications for
      future research and practice are provided.

PMID- 27893312
TI  - Resumenes al Espanol.

PMID- 27893311
TI  - More Job Services-Better Employment Outcomes: Increasing Job Attainment for
      People With IDD.
AB  - Job search, job placement, and on-the-job supports are valuable services provided
      to many people with intellectual and developmental disabilities (IDD) to obtain
      work in the community. Investigating those who were unemployed at the time of
      service entry, this study seeks to extend understanding about the effect of
      services. Using extant data, a sample of 39,277 people with IDD using Vocational
      Rehabilitation services were studied to understand the potential cumulative
      effects of these job-related services and individual characteristics on job
      attainment. Findings showed people with IDD of different demographic groups had
      different outcomes. Also, those receiving three job-related services were 16
      times more likely to obtain employment than the reference group. This study has
      wide implications for research, policy, and practice.

PMID- 27893314
TI  - Resumes en Francais.

PMID- 27893313
TI  - Issues in the Medication Management Process in People Who Have Intellectual and
      Developmental Disabilities: A Qualitative Study of the Caregivers' Perspective.
AB  - People who have intellectual and developmental disabilities (IDD) often rely on
      caregivers to assist in the medication management process. The aim of this study
      was to learn from caregivers, who are either family or support staff, what major
      issues arise throughout the process of managing medication and how these might be
      addressed. Problems identified by caregivers include (a) prescribers
      understanding of insurance and agency policies regarding medication utilization;
      (b) lack of continuity of care and accuracy of the medication record as well as
      clinical records;

PMID- 27893315
TI  - Presidential Address, 2016-Re-Membering the Gifts of Professional.

PMID- 27893316
TI  - Is It Worth It? Benefits in Research With Adults With Intellectual Disability.
AB  - Including adults with intellectual disability in research promotes direct
      benefits to participants and larger societal benefits. Stakeholders may have
      different views of what count as benefits and their importance. We compared views
      on benefits in research with adults with intellectual disability among adults
      with intellectual disability, family and friends, service providers, researchers,
      and institutional review board members. We found that adults with intellectual
      disability value direct and indirect research benefits, and want to participate
      in research that offers them. Other stakeholders generally see less value in
      direct benefits and predict more tempered interest in research participation as
      compared to adults with intellectual disability. To promote respectful research
      participation, research policy and practice should incorporate the views of
      adults with intellectual disability.

PMID- 27893317
TI  - The Relation Between Intellectual Functioning and Adaptive Behavior in the
      Diagnosis of Intellectual Disability.
AB  - Intellectual disability originates during the developmental period and is
      characterized by significant limitations both in intellectual functioning and in
      adaptive behavior as expressed in conceptual, social, and practical adaptive
      skills. In this article, we present a brief history of the diagnostic criteria of
      intellectual disability for both the DSM-5 and AAIDD. The article also (a)
      provides an update of the understanding of adaptive behavior, (b) dispels two
      thinking errors regarding mistaken temporal or causal link between intellectual
      functioning and adaptive behavior, (c) explains that there is a strong
      correlational, but no causative, relation between intellectual functioning and
      adaptive behavior, and (d) asserts that once a question of determining
      intellectual disability is raised, both intellectual functioning and adaptive
      behavior are assessed and considered jointly and weighed equally in the diagnosis
      of intellectual disability. We discuss the problems created by an inaccurate
      statement that appears in the DSM-5 regarding a causal link between deficits in
      intellectual functioning and adaptive behavior and propose an immediate revision
      to remove this erroneous and confounding statement.

PMID- 27893318
TI  - Sticks, Stones, and Stigma: Student Bystander Behavior in Response to Hearing the
      Word "Retard".
AB  - The present study explored the prevalence of the r-word in schools and students'
      bystander behavior in response to hearing the word. In total, 2,297 students from
      12 high schools across the country participated in this study. Results revealed
      the r-word was used frequently among high school students, most often toward
      individuals without intellectual disability (ID). Students were more likely to
      take an active bystander role when hearing the r-word used toward students with
      ID than when hearing it used toward students without ID. Students' gender and
      prosocialness also played a role in determining their bystander behavior in
      response to the r-word. This study has implications for reducing the use of the r
      word and the stigma associated with ID.

PMID- 27893321
TI  - Reply to D. Pulte et al.

PMID- 27893319
TI  - Insight into the machinery that oils chromatin dynamics.
AB  - The packaging of genetic information in form of chromatin within the nucleus
      provides cells with the ability to store and protect massive amounts of
      information within a compact space. Storing information within chromatin allows
      selective access to specific DNA sequences by regulating the various levels of
      chromatin structure from nucleosomes, to chromatin fibers, loops and topological
      associating domains (TADs) using mechanisms that are being progressively
      unravelled. However, a relatively unexplored aspect is the energetic cost of
      changing the chromatin configuration to gain access to DNA information. Among the
      enzymes responsible for regulating chromatin access are the ATP-dependent
      chromatin remodellers that act on nucleosomes and use the energy of ATP
      hydrolysis to make chromatin DNA more accessible. It is assumed that the ATP used
      by these enzymes is provided by the mitochondria or by cytoplasmic glycolysis. We
      hypothesize that though this may be the case for cells in steady state, when gene
      expression has to be globally reprogramed in response to externals signals or
      stress conditions, the cell directs energy production to the cell nucleus, where
      rapid chromatin reorganization is needed for cell survival. We discovered that in
      response to hormones a nuclear ATP synthesis mechanism is activated that
      utilizing ADP-ribose and pyrophosphate as substrates. 1 This extra view aims to
      put this process within its historical context, to describe the enzymatic steps
      in detail, to propose a possible structure of the ATP synthesising enzyme, and to
      shed light on how this may link to other reactions within the cell providing a
      perspective for future lines of investigation.

PMID- 27893322
TI  - Reply to M. Lambertini et al.

PMID- 27893323
TI  - ERCC1 as Predictor of Platinum Benefit in Non-Small-Cell Lung Cancer.

PMID- 27893324
TI  - Reply to B. De Bari et al and J. Widder et al.

PMID- 27893325
TI  - Basket Trials in Oncology: A Trade-Off Between Complexity and Efficiency.

PMID- 27893326
TI  - Randomized Prospective Biomarker Trial of ERCC1 for Comparing Platinum and
      Nonplatinum Therapy in Advanced Non-Small-Cell Lung Cancer: ERCC1 Trial (ET).
AB  - Purpose Retrospective studies indicate that expression of excision repair cross
      complementing group 1 (ERCC1) protein is associated with platinum resistance and
      survival in non-small-cell lung cancer (NSCLC). We conducted the first randomized
      trial, to our knowledge, to evaluate ERCC1 prospectively and to assess the
      superiority of nonplatinum therapy over platinum doublet therapy for ERCC1
      positive NSCLC as well as noninferiority for ERCC1-negative NSCLC. Patients and
      Methods This trial had a marker-by-treatment interaction phase III design, with
      ERCC1 (8F1 antibody) status as a randomization stratification factor. Chemonaive
      patients with NSCLC (stage IIIB and IV) were eligible. Patients with squamous
      histology were randomly assigned to cisplatin and gemcitabine or paclitaxel and
      gemcitabine; nonsquamous patients received cisplatin and pemetrexed or paclitaxel
      and pemetrexed. Primary end point was overall survival (OS). We also evaluated an
      antibody specific for XPF (clone 3F2). The target hazard ratio (HR) for patients
      with ERCC1-positive NSCLC was <= 0.78. Results Of patients, 648 were recruited
      (177 squamous, 471 nonsquamous). ERCC1-positive rates were 54.5% and 76.7% in
      nonsquamous and squamous patients, respectively, and the corresponding XPF
      positive rates were 70.5% and 68.5%. Accrual stopped early in 2012 for squamous
      patients because OS for nonplatinum therapy was inferior to platinum therapy
      (median OS, 7.6 months [paclitaxel and gemcitabine] v 10.7 months [cisplatin and
      gemcitabine]; HR, 1.46; P = .02). Accrual for nonsquamous patients halted in
      2013. Median OS was 8.0 (paclitaxel and pemetrexed) versus 9.6 (cisplatin and
      pemetrexed) months for ERCC1-positive patients (HR, 1.11; 95% CI, 0.85 to 1.44),
      and 10.3 (paclitaxel and pemetrexed) versus 11.6 (cisplatin and pemetrexed)
      months for ERCC1-negative patients (HR, 0.99; 95% CI, 0.73 to 1.33; interaction P
      = .64). OS HR was 1.09 (95% CI, 0.83 to 1.44) for XPF-positive patients, and 1.39
      (95% CI, 0.90 to 2.15) for XPF-negative patients (interaction P = .35). Neither
      ERCC1 nor XPF were prognostic: among nonsquamous patients, OS HRs for positive
      versus negative were ERCC1, 1.11 ( P = .32), and XPF, 1.08 ( P = .55). Conclusion
      Superior outcomes were observed for patients with squamous histology who received
      platinum therapy compared with nonplatinum chemotherapy; however, selecting
      chemotherapy by using commercially available ERCC1 or XPF antibodies did not
      confer any extra survival benefit.

PMID- 27893328
TI  - What's in a Name? Steady Progress in Staging Pancreatic Neuroendocrine Tumors.

PMID- 27893327
TI  - Radiation Therapy for Glioblastoma: American Society of Clinical Oncology
      Clinical Practice Guideline Endorsement of the American Society for Radiation
      Oncology Guideline.
AB  - Purpose The American Society for Radiation Oncology (ASTRO) produced an evidence
      based guideline on radiation therapy for glioblastoma. Because of its relevance
      to the ASCO membership, ASCO reviewed the guideline and applied a set of
      procedures and policies used to critically examine guidelines developed by other
      organizations. Methods The ASTRO guideline on radiation therapy for glioblastoma
      was reviewed for developmental rigor by methodologists. An ASCO endorsement panel
      updated the literature search and reviewed the content and recommendations.
      Results The ASCO endorsement panel determined that the recommendations from the
      ASTRO guideline, published in 2016, are clear, thorough, and based on current
      scientific evidence. ASCO endorsed the ASTRO guideline on radiation therapy for
      glioblastoma and added qualifying statements. Recommendations Partial-brain
      fractionated radiotherapy with concurrent and adjuvant temozolomide is the
      standard of care after biopsy or resection of newly diagnosed glioblastoma in
      patients up to 70 years of age. Hypofractionated radiotherapy for elderly
      patients with fair to good performance status is appropriate. The addition of
      concurrent and adjuvant temozolomide to hypofractionated radiotherapy seems to be
      safe and efficacious without impairing quality of life for elderly patients with
      good performance status. Reasonable options for patients with poor performance
      status include hypofractionated radiotherapy alone, temozolomide alone, or best
      supportive care. Focal reirradiation represents an option for select patients
      with recurrent glioblastoma, although this is not supported by prospective
      randomized evidence. Additional information is available at
      www.asco.org/glioblastoma-radiotherapy-endorsement and
      www.asco.org/guidelineswiki .

PMID- 27893329
TI  - Reaffirming and Clarifying the American Society of Clinical Oncology's Policy
      Statement on the Critical Role of Phase I Trials in Cancer Research and
      Treatment.

PMID- 27893330
TI  - Reply to M. Lambertini et al.

PMID- 27893333
TI  - Population-Level Survival for Patients With Chronic Myeloid Leukemia: Higher
      Survival in Sweden Than Internationally.

PMID- 27893334
TI  - Can Segmentectomy Still Be Proposed As an Alternative to Lobectomy in 2016?

PMID- 27893331
TI  - Multidisciplinary Approach to Novel Therapies in Cardio-Oncology Research
      (MANTICORE 101-Breast): A Randomized Trial for the Prevention of Trastuzumab
      Associated Cardiotoxicity.
AB  - Purpose The primary toxicity of trastuzumab therapy for human epidermal growth
      factor receptor 2-overexpressing (HER2-positive) breast cancer is dose
      independent cardiac dysfunction. Angiotensin-converting enzyme inhibitors and
      beta-blockers are recommended first-line agents for heart failure. We
      hypothesized that angiotensin-converting enzyme inhibitors and beta-blockers
      could prevent trastuzumab-related cardiotoxicity. Patients and Methods In this
      double-blinded, placebo-controlled trial, patients with HER2-positive early
      breast cancer were randomly assigned to receive treatment with perindopril,
      bisoprolol, or placebo (1:1:1) for the duration of trastuzumab adjuvant therapy.
      Patients underwent cardiac magnetic resonance imaging at baseline and post-cycle
      17 for the determination of left ventricular volumes and left ventricular
      ejection fraction (LVEF). Cardiotoxicity was evaluated as the change in indexed
      left ventricular end diastolic volume and LVEF. Results Thirty-three patients
      received perindopril, 31 received bisoprolol, and 30 received placebo. Baseline
      demographic, cancer, and cardiovascular profiles were similar between groups.
      Study drugs were well tolerated with no serious adverse events. After 17 cycles
      of trastuzumab, indexed left ventricular end diastolic volume increased in
      patients treated with perindopril (+7 +/- 14 mL/m2), bisoprolol (+8 mL +/- 9
      mL/m2), and placebo (+4 +/- 11 mL/m2; P = .36). In secondary analyses,
      trastuzumab-mediated decline in LVEF was attenuated in bisoprolol-treated
      patients (-1 +/- 5%) relative to the perindopril (-3 +/- 4%) and placebo (-5 +/-
      5%) groups ( P = .001). Perindopril and bisoprolol use were independent
      predictors of maintained LVEF on multivariable analysis. Conclusion Perindopril
      and bisoprolol were well tolerated in patients with HER2-positive early breast
      cancer who received trastuzumab and protected against cancer therapy-related
      declines in LVEF; however, trastuzumab-mediated left ventricular remodeling-the
      primary outcome-was not prevented by these pharmacotherapies.

PMID- 27893332
TI  - Outcome of Men With Relapse After Adjuvant Carboplatin for Clinical Stage I
      Seminoma.
AB  - Purpose Adjuvant carboplatin is one of three management strategies that may
      follow inguinal orchiectomy in clinical stage I seminoma. However, little is
      known about the outcome of patients who experience a relapse after such
      treatment. Patients and Methods Data from 185 patients who relapsed after
      adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups
      from 20 countries were collected and retrospectively analyzed. Primary outcomes
      were disease-free survival and overall survival. Secondary outcomes were time to,
      stage at, and treatment of relapse as well as rate of subsequent relapses.
      Results With a median follow-up of 53 months (95% CI, 48 to 60 months) the 5-year
      disease-free survival was 82% (95% CI, 77% to 89%), and the 5-year overall
      survival was 98% (95% CI, 95% to 100%). The median time from orchiectomy to
      relapse was 19 months (95% CI, 17 to 23 months); 15% (95% CI, 10% to 21%) of
      relapses occurred > 3 years after treatment. The majority of relapses were
      detected by computed tomography scan during routine follow-up, 98% in the
      International Germ Cell Cancer Collaborative Group good prognosis group.
      Chemotherapy was administered to 92% of patients, mostly as standard first-line
      treatment corresponding to stage; 8% of patients had additional local treatments.
      Only 28 patients experienced a second relapse. At last follow-up, 174 (94%) of
      185 patients were alive without disease, and four patients with disease. Seven
      patients died, three of whom due to progressive disease. Conclusion Within the
      limitations of a retrospective analysis, the results suggest that the majority of
      patients who experience a relapse after adjuvant carboplatin for clinical stage I
      seminoma can be successfully treated with a cisplatin-based chemotherapy regimen
      adequate for stage. Because 15% of the relapses occurred > 3 years after adjuvant
      treatment, a minimum of 5 years follow-up is recommended.

PMID- 27893335
TI  - Debated Role of Ovarian Protection With Gonadotropin-Releasing Hormone Agonists
      During Chemotherapy for Preservation of Ovarian Function and Fertility in Women
      With Cancer.

PMID- 27893336
TI  - Lobectomy or Sublobectomy for Small Non-Small-Cell Lung Cancer: The Question
      Remains.

PMID- 27893337
TI  - Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors
      Versus Noncancer Controls: Evidence for Accelerated Aging?
AB  - Purpose The sequelae of cancer treatment may increase systemic inflammation and
      create a phenotype at increased risk of functional decline and comorbidities,
      leading to premature mortality. Little is known about how this trajectory
      compares with natural aging among peers of the same age without cancer. This
      longitudinal study investigated proinflammatory cytokines and comorbidity
      development over time among breast cancer survivors and a noncancer control
      group. Methods Women (N = 315; 209 with breast cancer and 106 in the control
      group) were recruited at the time of their work-up for breast cancer; they
      completed the baseline questionnaire, interview, and blood draw
      (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis
      factor-alpha, and IL-1beta). Measures were repeated 6 and 18 months after primary
      cancer treatment (cancer survivors) or within a comparable time frame (control
      group). Results There were no baseline differences in comorbidities or cytokines
      between survivors and the control group. Over time, breast cancer survivors had
      significantly higher tumor necrosis factor-alpha and IL-6 compared with the
      control group. Survivors treated with surgery, radiation, and chemotherapy
      accumulated a significantly greater burden of comorbid conditions and suffered
      greater pain associated with inflammation over time after cancer treatment than
      did the control group. Conclusion Survivors who had multimodal treatment had
      higher cytokines and comorbidities, suggestive of accelerated aging.
      Comorbidities were related to inflammation in this sample, which could increase
      the likelihood of premature mortality. Given that many comorbidities take years
      to develop, future research with extended follow-up beyond 18 months is necessary
      to examine the evidence of accelerated aging in cancer survivors and to determine
      the responsible mechanisms.

PMID- 27893339
TI  - Psychopathy in Everyday Life.
AB  - Psychopathy is a spectrum of possibilities linked with survival drives. It
      appears in commonly accepted forms in everyday life and more egregious,
      devastating ways as well. Often extreme manifestations of psychopathy become part
      of everyday existence, almost taken as normal while its cumulative
      destructiveness mounts. This paper explores a range of psychopathic states in
      individuals and groups, including positive and negative contributions these
      tendencies can make. Psychopathy in individuals and culture interweave in many
      ways, and some of the latter are discussed.

PMID- 27893338
TI  - Seroprevalence and Risk Factors of Toxoplasma gondii Infection in Farmed Raccoon
      Dogs (Nyctereutes procyonoides) in China.
AB  - Toxoplasma gondii, an obligate intracellular apicomplexan parasite, can infect
      homoiothermal vertebrate animals, including raccoon dogs (Nyctereutes
      procyonoides). Regretfully, data on T. gondii infection in raccoon dogs were
      limited in China. Therefore, to investigate the seroprevalence and to evaluate
      risk factors for T. gondii infection in raccoon dogs, a total of 1181 raccoon dog
      blood samples were collected from Jilin and Shandong provinces, China, from
      September to December 2014. The antibodies of T. gondii were examined using the
      modified agglutination test. Overall, the seroprevalence of T. gondii infection
      was 8.64% in the examined raccoon dogs. The prevalences of T. gondii infection
      were different among cities (ranging from 2.96% in Yantai to 17.62% in Qingdao),
      genders (female: 7.58%; male: 9.22%), and ages (young: 8.53%; subadult: 7.71%;
      adult: 7.73%). Region was considered as an important risk factor for T. gondii
      infection in this study. This is the first report of T. gondii infection in
      raccoon dogs in China, providing baseline information for prevention and control
      of T. gondii infection in raccoon dogs in Jilin and Shandong provinces, China.

PMID- 27893341
TI  - Index of Contents: Psychoanalytic Review, Volume 103.

PMID- 27893342
TI  - Person-Environment Mergence and Separation: Otto Rank's Psychology of Emotion,
      Personality, and Culture.
AB  - Between 1924 and 1939 Otto Rank put forward three major elements of a
      comprehensive theoretical edifice that has yet to be fully articulated. These are
      conceptually linked by the fundamental importance of person-environment mergence
      and separation. Rank's theory of emotions highlights anxiety as the affect of
      separation, and guilt as the feeling that binds the individual to others. His
      personality theory distinguishes between the partialist, who responds to life
      fear with identification, and the totalist, who responds to death fear with
      projection. His cultural psychology contrasts primal collectivism with
      contemporary individualism, which orients the person toward individual
      immortality striving. Individualism has produced problematic self-consciousness
      and neuroticism, in the face of which Rank struggled to find a new psychology.

PMID- 27893344
TI  - From Hallucination to Fiction: The Invention of Meaning in Psychosis.
AB  - Taking their inspiration from a case history, the authors explore the effects of
      a writing workshop led by a professional writer for patients in a psychiatric
      hospital. This workshop allowed different modes of transference to unfold:
      transference to the analyst-therapist, transference to the writer who led the
      workshop, and transference to the other members of the group. The writing
      activity created conditions in which there could be a movement from hallucination
      to delusion-a delusion expressed in fiction through the act of writing. Psychotic
      patients "invent" a writing that remains unfinished and that relates to the
      experiences of persecution. Writing thus makes it possible for them to tolerate
      language, through its transformation into writing.

PMID- 27893345
TI  - Quo Vadis? The Future of Psychoanalysis.
AB  - Although contemporary psychoanalysis is split into different schools and
      traditions, there is growing support for some of the main tenets of contemporary
      psychodynamic thinking from attachment theory, infant research, developmental
      psychopathology, new models of motivation, the neuroscience of emotions and
      emotional regulation, and the discovery of different implicit and explicit memory
      systems. These tenets, which psychodynamic clinicians of all stripes encounter in
      their daily work with clients, are the following: (1) that large footprints are
      left over from infancy and childhood which involved insensitive, intrusive,
      frightening, or shaming care; (2) the carryover of these relational experiences
      into adulthood are expressed as unconscious expectations and attributions we make
      of others (transference and countertransference; (3) defensive processes and
      emotional regulation and deregulatory patterns develop to cope with these
      unhealthy relations. Many findings from infant research, attachment theory, and
      new models of motivation and neuroscience have developed alongside the
      intersubjective and relational turn in psychoanalysis in the last sixty years. To
      different degrees this new developmental science has been incorporated into the
      relational field. This essay is a plea to incorporate this new science in the
      teaching of psychodynamic psychotherapy in order to create a dialogue among
      different relational and intersubjective traditions in psychoanalysis that could
      reduce the splintering and support efforts toward integration.

PMID- 27893346
TI  - The Preoedipal and Oedipal Structure of Termination: An In-depth Case Study.
AB  - Much has been written about the Oedipus complex as a central organizing focus for
      the understanding of early developmental attainments as well as for the
      structuring of the personality, but nowhere are triangular forces more vitally
      active, clinically, than in the termination phase. The decision to end, once
      agreed upon, typically sets in motion a symmetrical process in which two dynamics
      occur concurrently. First, what drives the termination is a mourning process in
      which the primary task is to relinquish the analyst as a transference object and
      to establish the analyst as an internal object. In parallel, oedipal structures
      take hold of the termination process so that the final working-through and the
      resolution of the transference/countertransference can be maximized-with the goal
      of integration. An eight-year, four-times-a-week analytic psychotherapy on the
      couch is described to illustrate the critical role of triangulation dynamics in
      termination. Using in-depth transcripts of dream and sessional material, the
      author highlights a number of conscious and unconscious resistances in the
      patient to this phase of work that were particular to his perverse oedipal
      pathology. Ron Britton's concept of an organized oedipal illusion or an oedipal
      delusion as defenses against the termination phase proved helpful to both patient
      and psychotherapist in negotiating some of the heightened emotional aspects of
      the final working-through.

PMID- 27893347
TI  - Asymptomatic infections in blood donors harbouring Plasmodium: an invisible risk
      detected by molecular and serological tools.
AB  - BACKGROUND: Transfusion-transmitted malaria due to asymptomatic Plasmodium
      infections is a challenge for blood banks. There is a lack of data on the
      prevalence of asymptomatic infected blood donors and the incidence of transfusion
      transmitted malaria in low endemicity areas worldwide. We estimated the frequency
      of blood donors harbouring Plasmodium in an area in which asymptomatic infections
      have been reported. MATERIAL AND METHODS: To estimate the frequency of blood
      donors harbouring Plasmodium we used microscopy and molecular tools. Serological
      tests were applied to measure the exposure of candidates to Plasmodium antigens.
      Venous blood was collected from 91 candidates attending the "Pro-Sangue" Blood
      Centre Foundation in Sao Paulo, who lived in the municipality of Juquitiba, Sao
      Paulo, Brazil, where sporadic autochthonous cases of malaria have been described.
      Blood samples were used for parasitological, molecular and serological studies.
      RESULTS: Among the 91 samples examined, rare Plasmodium forms were observed in
      two donors. Genus real-time polymerase chain reaction analysis demonstrated
      Plasmodium amplification in three candidates and species-specific nested
      polymerase chain reaction identified P. malariae in two. ELISA-IgG was reactive
      in 42.9% of samples for P. vivax (Pv-MSP119) and in 6.6% for P. falciparum (Pf
      Zw). ELISA-IgM was reactive in 2.2% of samples for P. vivax and in 4.4% for P.
      falciparum. An indirect immunofluorescence assay was reactive for P. malariae in
      15.4% of cases. DISCUSSION: Reservoirs of Plasmodium represent a challenge for
      blood banks, since studies have shown that high levels of submicroscopic
      infections can occur in low transmission areas. The risk of transfusion
      transmitted malaria presented here points to the need to conduct molecular
      investigations of candidate donors with any positive malarial antibody test.

PMID- 27893348
TI  - Cost-utility and budget impact of methylene blue-treated plasma compared to
      quarantine plasma.
AB  - BACKGROUND: Methylene blue and visible light treatment and quarantine are two
      methods used to reduce adverse events, mostly infections, associated with the
      transfusion of fresh-frozen plasma. The objective of this study was to estimate
      and compare the budget impact and cost-utility of these two methods from a
      payer's perspective. MATERIALS AND METHODS: A budget impact and cost-utility
      model simulating the risks of hepatitis B virus, hepatitis C virus,
      cytomegalovirus, a West Nile virus-like infection, allergic reactions and febrile
      non-haemolytic transfusion reactions achieved using plasma treated with methylene
      blue and visible light (MBP) and quarantine plasma (QP) was constructed for
      Spain. QP costs were estimated using data from one blood centre in Spain and
      published literature. The costs of producing fresh-frozen plasma from whole
      blood, apheresis plasma, and multicomponent apheresis, and separately for passive
      and active methods of donor recall for QP were included. Costs and outcomes over
      a 5-year and lifetime time horizon were estimated. RESULTS: Compared to passive
      QP, MBP led to a net increase of ? 850,352, and compared to active QP, MBP led to
      a net saving of ? 5,890,425 over a 5-year period. Compared to passive QP, MBP
      increased the cost of fresh-frozen plasma per patient by ? 7.21 and had an
      incremental cost-utility ratio of ? 705,126 per quality-adjusted life-year.
      Compared to active QP, MBP reduced cost by ? 50.46 per patient and was more
      effective. DISCUSSION: Plasma collection method and quarantine approach had the
      strongest influence on the budget impact and cost-utility of MBP. If QP relies on
      plasma from whole blood collection and passive quarantine, it is less costly than
      MBP. However, MPB was estimated to be more effective than QP in all analyses.

PMID- 27893349
TI  - Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood,
      with and without leucofiltration, with and without ionising radiation.
AB  - BACKGROUND: Storage lesion, including microparticle formation, has been partially
      characterised in whole blood, but not in all combinations of pre-storage
      leucofiltration and/or irradiation. MATERIALS AND METHODS: Single-donor whole
      blood products were processed into four subunits: with and without
      leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-,
      and erythrocyte-derived microparticles and free haemoglobin were measured
      periodically throughout 42 days of storage. RESULTS: Pre-storage leucofiltration
      substantially reduced platelet- and leucocyte-derived microparticle counts
      throughout storage. Irradiation, in contrast, had no significant effect on
      microparticle counts. A gate for all microparticles showed a substantial time
      dependent increase in unfiltered whole blood. A time-dependent increase in free
      haemoglobin was greatest in unfiltered, irradiated whole blood. DISCUSSION: This
      study indicates that leucofiltration can prevent the formation of leucocyte- and
      platelet-derived microparticles, and might reduce haemolysis in irradiated whole
      blood, either by removing factors that provoke haemolysis, or by selective
      retention of senescent or effete red cells most prone to haemolysis.

PMID- 27893350
TI  - The Bleeding Assessment Tool and laboratory data in the characterisation of a
      female with inherited haemophilia A.

PMID- 27893351
TI  - Management of iron overload in myelodysplastic syndromes: combined deferasirox
      and deferoxamine in a patient with liver disease.

PMID- 27893352
TI  - Prevalence of antibodies to a new histo-blood system: the FORS system.
AB  - BACKGROUND: In 1987, three unrelated English families were reported with a
      putative blood subgroup called Apae. Swedish researchers later found evidence
      leading to abolishment of the Apae subgroup and establishment instead of the FORS
      blood group system (System 31 - ISBT, 2012). It is important to know the
      prevalence of antibodies in order to make the best decisions in transfusion
      medicine. Cells expressing the Forssman saccharide, such as sheep erythrocytes,
      are needed to detect the anti-Forssman antibody. The aim of this study was to
      define the prevalence of human anti-Forssman antibody. MATERIALS AND METHODS:
      Plasma samples from 800 individuals were studied. Sheep erythrocytes or Forssman
      "kodecytes" were mixed with the plasma samples using the tube technique. Plasma
      from an Apae individual was used as a negative control and monoclonal anti
      Forssman antibody (M1/22.25.8HL cell line supernatant) was used as the positive
      control. RESULTS: Of the 800 individuals tested, one was negative for the
      presence of anti-Forssman antibody. We compared the anti-Forssman antibody
      reaction pattern between genders and found that males have weaker reactions than
      females, both at room temperature (p=0.026) and at 37  degrees C (p=0.043). We
      also investigated the reaction pattern of anti-Forssman antibody in relation to
      ABO and Rh blood group types without finding any significant differences.
      DISCUSSION: Sheep erythrocytes are suitable for searching for human anti-Forssman
      antibody. The quantity of anti-Forssman antibodies in plasma is higher in females
      than in males. In the population (n=800) studied here, we found one individual
      lacking the anti-Forssman antibody. These results contribute to the data already
      published, confirming that FORS is a rare blood group.

PMID- 27893353
TI  - Low-dose erythropoietin treatment is not associated with clinical benefits in
      severely anaemic Jehovah's Witnesses: a plea for a change.
AB  - BACKGROUND: Jehovah's Witnesses who refuse blood transfusion have high mortality.
      Erythropoietin (EPO) has been used as an alternative to blood transfusion. The
      optimal dosing of EPO in anaemic Jehovah's Witnesses is unknown. The aim of our
      study was to evaluate the clinical benefits of treatment with a low dose (<600
      IU/kg/week) of epoietin beta (EPO-beta). MATERIALS AND METHODS: This was an
      observational study, retrospectively considering a 10-year period during which
      3,529 adult Jehovah's Witnesses with a total of 10,786 hospital admissions were
      identified from databases of four major public hospitals in New Zealand. Patients
      with severe symptomatic anaemia (haemoglobin <80 g/L) who were unable to tolerate
      physical activity were included in the study. Patients treated without EPO were
      assigned to the conventional therapy group and those treated with EPO to the EPO
      treatment group. RESULTS: Ninety-one Jehovah's Witnesses met the eligibility
      criteria. Propensity score matching yielded a total of 57 patients. Patients
      treated with conventional therapy and those treated with EPO had similar
      durations of severe anaemia (average difference 6.25 days, 95% confidence
      interval [CI]: -3.77-16.27 days; p=0.221). The mortality rate among Jehovah's
      Witnesses treated with conventional therapy was 4.68 per year (95% CI: 2.23
      9.82), while that in those treated with EPO was 2.77 per year (95% CI: 0.89
      8.60). Treatment with EPO was associated with a mortality ratio of 0.59 (95% CI:
      0.1-2.6; p=0.236). Both groups of patients had similar in-hospital survival
      (p=0.703). DISCUSSION: Treatment with low-dose EPO-beta was not associated with
      either shorter duration of severe anaemia or a reduction in mortality.

PMID- 27893354
TI  - Summary report of the First International Conference on inhibitors in haemophilia
      A.

PMID- 27893356
TI  - Single-stranded DNA aptamer targeting and neutralization of anti-D alloantibody:
      a potential therapeutic strategy for haemolytic diseases caused by Rhesus
      alloantibody.
AB  - BACKGROUND: Rhesus (Rh) D antigen is the most important antigen in the Rh blood
      group system because of its strong immunogenicity. When RhD-negative individuals
      are exposed to RhD-positive blood, they may produce anti-D alloantibody,
      potentially resulting in delayed haemolytic transfusion reactions and Rh
      haemolytic disease of the foetus and newborn, which are difficult to treat.
      Inhibition of the binding of anti-D antibody with RhD antigens on the surface of
      red blood cells may effectively prevent immune haemolytic diseases. MATERIALS AND
      METHODS: In this study, single-stranded (ss) DNA aptamers, specifically binding
      to anti-D antibodies, were selected via systematic evolution of ligands by
      exponential enrichment (SELEX) technology. After 14 rounds of selection, the
      purified ssDNA was sequenced using a Personal Genome Machine system.
      Haemagglutination inhibition assays were performed to screen aptamers for
      biological activity in terms of blocking antigen-antibody reactions: the affinity
      and specificity of the aptamers were also determined. RESULTS: In addition to
      high specificity, the aptamers which were selected showed high affinity for anti
      D antibodies with dissociation constant (Kd) values ranging from 51.46+/-14.90 to
      543.30+/-92.59 nM. By the combined use of specific ssDNA aptamer 7 and auxiliary
      ssDNA aptamer 2, anti-D could be effectively neutralised at low concentrations of
      the aptamers. DISCUSSION: Our results demonstrate that ssDNA aptamers may be a
      novel, promising strategy for the treatment of delayed haemolytic transfusion
      reactions and Rh haemolytic disease of the foetus and newborn.

PMID- 27893355
TI  - Performance evaluation study of ID CORE XT, a high throughput blood group
      genotyping platform.
AB  - BACKGROUND: Traditionally, red blood cell antigens have been identified using
      serological methods, but recent advances in molecular biology have made the
      implementation of methods for genetic testing of most blood group antigens
      possible. The goal of this study was to validate the performance of the ID CORE
      XT blood group typing assay. MATERIALS AND METHODS: One thousand independent
      samples from donors, patients and neonates were collected from three research
      institutes in Spain and the Netherlands. DNA was extracted from EDTA
      anticoagulated blood. The data were processed with the ID CORE XT to obtain the
      genotypes and the predicted blood group phenotypes, and results were compared to
      those obtained with well-established serological and molecular methods. All 1,000
      samples were typed for major blood group antigens (C, c, E, e, K) and 371-830
      samples were typed for other antigens depending on the rarity and availability of
      serology comparators. RESULTS: The incorrect call rate was 0%. Four "no calls"
      (rate: 0.014%) were resolved after repetition. The sensitivity of ID CORE XT for
      all phenotypes was 100% regarding serology. There was one discrepancy in E-
      antigen and 33 discrepancies in Fyb- antigen. After bidirectional sequencing, all
      discrepancies were resolved in favour of ID CORE XT (100% specificity). ID CORE
      XT detected infrequent antigens of Caucasians in the sample as well as rare
      allelic variants. DISCUSSION: In this evaluation performed in an extensive sample
      following the European Directive, the ID CORE XT blood genotyping assay performed
      as a reliable and accurate method for correctly predicting the genotype and
      phenotype of clinically relevant blood group antigens.

PMID- 27893357
TI  - FUT1 mutations responsible for the H-deficient phenotype in the Polish
      population, including the first example of an abolished start codon.

PMID- 27893358
TI  - The price of enhanced half-life factor IX.

PMID- 27893359
TI  - Collection of umbilical cord blood for banking: collection rate and factors
      influencing collection.

PMID- 27893360
TI  - Vaccine-Preventable Diseases In Pediatric Patients: A Review Of Measles, Mumps,
      Rubella, And Varicella.
AB  - Vaccine-preventable diseases such as measles, mumps, rubella, and varicella
      continue to plague children and adults worldwide. Although public health programs
      have helped decrease the prevalence and sequelae of these diseases, outbreaks
      still occur. To limit the spread of these diseases, emergency clinicians must be
      able to readily identify the characteristic presentations of the rashes
      associated with measles, rubella, and varicella, as well as the common presenting
      features associated with mumps. Diagnostic laboratory studies are not usually
      necessary, as a complete history and physical examination usually lead to an
      accurate diagnosis. Treatment for these vaccine-preventable diseases usually
      consists of supportive care, but, in some cases, severe complications and death
      may occur. This issue provides a review of the clinical features, differential
      diagnoses, potential complications, and treatment options for measles, mumps,
      rubella, and varicella.

PMID- 27893362
TI  - Pure Abstraction.
AB  - Vincent Pucciarelli's imagery falls into the category of pure digital
      abstraction. The only requirements for his images are shapes, lines, colors,
      patterns, and the viewer's own boundless imagination.

PMID- 27893363
TI  - Using Art to Visualize Cellular Environments: An Interview with David Goodsell.
AB  - David Goodsell creates paintings of the inside of cells as well as other
      molecular scale objects. His work reveals cellular structures that are
      scientifically accurate and engaging to the human eye. This interview explores
      how he brings to life that which we cannot see and how the scale and detail of
      his work produces a more complete understanding of and engagement with these
      complex structures.

PMID- 27893361
TI  - Regulatory changes in two chemoreceptor genes contribute to a Caenorhabditis
      elegans QTL for foraging behavior.
AB  - Natural isolates of C. elegans differ in their sensitivity to pheromones that
      inhibit exploratory behavior. Previous studies identified a QTL for pheromone
      sensitivity that includes alternative alleles of srx-43, a chemoreceptor that
      inhibits exploration through its activity in ASI sensory neurons. Here we show
      that the QTL is multigenic and includes alternative alleles of srx-44, a second
      chemoreceptor gene that modifies pheromone sensitivity. srx-44 either promotes or
      inhibits exploration depending on its expression in the ASJ or ADL sensory
      neurons, respectively. Naturally occurring pheromone insensitivity results in
      part from previously described changes in srx-43 expression levels, and in part
      from increased srx-44 expression in ASJ, which antagonizes ASI and ADL.
      Antagonism between the sensory neurons results in cellular epistasis that is
      reflected in their transcription of insulin genes that regulate exploration.
      These results and genome-wide evidence suggest that chemoreceptor genes may be
      preferred sites of adaptive variation in C. elegans.

PMID- 27893365
TI  - Design and Choice of Visual Display Solutions in the Training Domain.
AB  - Visual display solutions are a key element of computer-based system architectures
      intended for human-system interaction. Particularly in the training domain, an
      ill-matched visual display can render a system unusable or ineffectual, which may
      cause underutilization or a negative transfer of training. This article outlines
      a set of approaches and best practices used in research efforts focused on the
      design of novel military training systems.

PMID- 27893364
TI  - Visualizing Rugby Game Styles Using Self-Organizing Maps.
AB  - Rugby coaches and analysts often use notational data describing match events to
      assess their team's performance and to devise strategic plans for upcoming
      matches. However, given the volume and complexity of the data available, it is
      difficult for them to recognize high-dimensional relationships among the
      available performance variables. A nonlinear approach using self-organizing maps
      (SOM) can help visualize the performance of a team and its opponents as well as
      the subsequent suitability of certain game styles, given the style of the
      opponent.

PMID- 27893366
TI  - HuSIS: A Dedicated Space for Studying Human Interactions.
AB  - To support the study of effective human-surrogate interaction techniques and
      modalities, the Office of Naval Research awarded an equipment grant to support
      the development of a Human-Surrogate Interaction Space (HuSIS) at the University
      of Central Florida in the Institute for Simulation & Training. The HuSIS consists
      of a dedicated physical space, structures, and components designed specifically
      for carrying out controlled studies related to human-surrogate interactions. This
      article describes the motivation, design, and realization of the HuSIS and the
      benefits of the common data-collection and analysis framework developed for HuSIS
      research.

PMID- 27893367
TI  - Interactive Crowd-Behavior Learning for Surveillance and Training.
AB  - The proposed interactive crowd-behavior learning algorithms can be used to
      analyze crowd videos for surveillance and training applications. The authors'
      formulation combines online tracking algorithms from computer vision, nonlinear
      pedestrian motion models from computer graphics, and machine learning techniques
      to automatically compute trajectory-level pedestrian behaviors for each agent in
      the video. These learned behaviors are used to automatically detect anomalous
      behaviors, perform motion segmentation, and generate realistic behaviors for
      virtual reality training applications.

PMID- 27893368
TI  - BKViz: A Basketball Visual Analysis Tool.
AB  - The amount of data available in the sports field is difficult for coaches,
      analysts, and players to comprehend using classic analytics methods. Thus, new
      methods are necessary to help users break down that information and analyze it at
      a deeper level. The BKViz visual analytics system focuses on individual
      basketball games using classic and novel methods to reveal how players perform
      together and as individuals. The information is presented in interactive
      visualizations that allow immediate user feedback.

PMID- 27893370
TI  - Network Visualization as a Higher-Order Visual Analysis Tool.
AB  - The transformation of data into visuals that are as effective and engaging as
      possible for compelling presentation is an emerging topic in information
      visualization research. With this goal in mind, several data-analysis system
      approaches offer a higher-order network visualization that map insights rather
      than raw data. Knowledge visualization or externalization in the form of small,
      focused diagrams can communicate insights as well as help analysts structure
      their reasoning process.

PMID- 27893369
TI  - Customized Body Mapping to Facilitate the Ergonomic Design of Sportswear.
AB  - A successful high-performance sportswear design that considers human factors
      should result in a significant increase in thermal comfort and reduce energy
      loss. The authors describe a body-mapping approach that facilitates the effective
      ergonomic design of sportswear. Their general framework can be customized based
      on the functional requirements of various sports and sportswear, the desired
      combination and selection of mapping areas for the human body, and customized
      quantitative data distribution of target physiological indicators.

PMID- 27893371
TI  - Efficient High-Dimensional, Edge-Aware Filtering.
AB  - Traditional computer graphics filters are agnostic to the concept of objects and
      the transition between objects (edges), but image filters need to take edges into
      account in order to produce high-quality, artifact-free, beautifully formed
      images. Eduardo S.L. Gastal's dissertation focuses on efficient algorithms for
      performing edge-aware image and video filtering. The techniques he describes here
      leverage the known relationship between edge-aware filtering and high-dimensional
      spaces and are capable of achieving real-time performance in high-resolution
      data.

PMID- 27893373
TI  - Robust Color Guided Depth Map Restoration.
AB  - One of the most challenging issues in color guided depth map restoration is the
      inconsistency between color edges in guidance color images and depth
      discontinuities on depth maps. This makes the restored depth map suffer from
      texture copy artifacts and blurring depth discontinuities. To handle this
      problem, most state-of-the-art methods design complex guidance weight based on
      guidance color images and heuristically make use of the bicubic interpolation of
      the input depth map. In this paper, we show that using bicubic interpolated depth
      map can blur depth discontinuities when the upsampling factor is large and the
      input depth map contains large holes and heavy noise. In contrast, we propose a
      robust optimization framework for color guided depth map restoration. By adopting
      a robust penalty function to model the smoothness term of our model, we show that
      the proposed method is robust against the inconsistency between color edges and
      depth discontinuities even when we use simple guidance weight. To the best of our
      knowledge, we are the first to solve this problem with a principled mathematical
      formulation rather than previous heuristic weighting schemes. The proposed robust
      method performs well in suppressing texture copy artifacts. Moreover, it can
      better preserve sharp depth discontinuities than previous heuristic weighting
      schemes. Through comprehensive experiments on both simulated data and real data,
      we show promising performance of the proposed method.

PMID- 27893375
TI  - Liver Segmentation on CT and MR Using Laplacian Mesh Optimization.
AB  - OBJECTIVE: The purpose of this paper is to describe a semiautomated segmentation
      method for the liver and evaluate its performance on CT-scan and MR images.
      METHODS: First, an approximate 3-D model of the liver is initialized from a few
      user-generated contours to globally outline the liver shape. The model is then
      automatically deformed by a Laplacian mesh optimization scheme until it precisely
      delineates the patient's liver. A correction tool was implemented to allow the
      user to improve the segmentation until satisfaction. RESULTS: The proposed method
      was tested against 30 CT-scans from the SLIVER07 challenge repository and 20 MR
      studies from the Montreal University Hospital Center, covering a wide spectrum of
      liver morphologies and pathologies. The average volumetric overlap error was 5.1%
      for CT and 7.6% for MRI and the average segmentation time was 6 min. CONCLUSION:
      The obtained results show that the proposed method is efficient, reliable, and
      could effectively be used routinely in the clinical setting. SIGNIFICANCE: The
      proposed approach can alleviate the cumbersome and tedious process of slice-wise
      segmentation required for precise hepatic volumetry, virtual surgery, and
      treatment planning.

PMID- 27893376
TI  - Modulated Excitation Imaging System for Intravascular Ultrasound.
AB  - Advances in methodologies and tools often lead to new insights into
      cardiovascular diseases. Intravascular ultrasound (IVUS) is a well-established
      diagnostic method that provides high-resolution images of the vessel wall and
      atherosclerotic plaques. High-frequency (>50 MHz) ultrasound enables the spatial
      resolution of IVUS to approach that of optical imaging methods. However, the
      penetration depth decreases when using higher imaging frequencies due to the
      greater acoustic attenuation. An imaging method that improves the penetration
      depth of high-resolution IVUS would, therefore, be of major clinical importance.
      Modulated excitation imaging is known to allow ultrasound waves to penetrate
      further. This paper presents an ultrasound system specifically for modulated
      excitation-based IVUS imaging. The system incorporates a high-voltage waveform
      generator and an image processing board that are optimized for IVUS applications.
      In addition, a miniaturized ultrasound transducer has been constructed using a
      Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystal to improve the ultrasound characteristics.
      The results show that the proposed system was able to provide increases of 86.7%
      in penetration depth and 9.6 dB in the signal-to-noise ratio for 60 MHz IVUS. In
      vitro tissue samples were also investigated to demonstrate the performance of the
      system.

PMID- 27893377
TI  - High-Performance CAD-CTC Scheme Using Shape Index, Multiscale Enhancement
      Filters, and Radiomic Features.
AB  - OBJECTIVE: Computer-aided detection (CAD) systems for computed tomography
      colonography (CTC) can automatically detect colorectal polyps. The main problem
      of currently developed CAD-CTC systems is the numerous false positives (FPs)
      caused by the existence of complicated colon structures (e.g., haustral fold,
      residual fecal material, inflation tube, and ileocecal valve). This study
      proposes a CAD-CTC scheme using shape index, multiscale enhancement filters, and
      radiomic features to address the FP issue. METHODS: Shape index and multiscale
      enhancement filter calculated in the Gaussian smoothed geodesic distance field
      are combined to generate the polyp candidates. A total of 440 well-defined
      radiomic features collected from previous radiomic studies and 200 newly
      developed radiomic features are used to construct a supervised classification
      model to reduce the numerous FPs. RESULTS: The proposed CAD-CTC scheme was
      evaluated on 152 oral contrast-enhanced CT datasets from 76 patients with 103
      polyps >=5 mm. The detection results were 98.1% and 95.3% by-polyp sensitivity
      and per-scan sensitivity, respectively, with the same FP rate of 1.3 FPs per
      dataset for polyps >=5 mm. CONCLUSION: Experimental results indicate that the
      proposed CAD-CTC scheme can achieve high sensitivity while maintaining a low FP
      rate. SIGNIFICANCE: The proposed CAD-CTC scheme would be a beneficial tool in
      clinical colon examination.

PMID- 27893378
TI  - Semi-supervised Stacked Label Consistent Autoencoder for Reconstruction and
      Analysis of Biomedical Signals.
AB  - OBJECTIVE: An autoencoder-based framework that simultaneously reconstruct and
      classify biomedical signals is proposed. Previous work has treated reconstruction
      and classification as separate problems. This is the first study that proposes a
      combined framework to address the issue in a holistic fashion. METHODS: For
      telemonitoring purposes, reconstruction techniques of biomedical signals are
      largely based on compressed sensing (CS); these are "designed" techniques where
      the reconstruction formulation is based on some "assumption" regarding the
      signal. In this study, we propose a new paradigm for reconstruction-the
      reconstruction is "learned," using an autoencoder; it does not require any
      assumption regarding the signal as long as there is sufficiently large training
      data. But since the final goal is to analyze/classify the signal, the system can
      also learn a linear classification map that is added inside the autoencoder. The
      ensuing optimization problem is solved using the Split Bregman technique.
      RESULTS: Experiments were carried out on reconstructing and classifying
      electrocardiogram (ECG) (arrhythmia classification) and EEG (seizure
      classification) signals. CONCLUSION: Our proposed tool is capable of operating in
      a semi-supervised fashion. We show that our proposed method is better in
      reconstruction and more than an order magnitude faster than CS based methods; it
      is capable of real-time operation. Our method also yields better results than
      recently proposed classification methods. SIGNIFICANCE: This is the first study
      offering an alternative to CS-based reconstruction. It also shows that the
      representation learning approach can yield better results than traditional
      methods that use hand-crafted features for signal analysis.

PMID- 27893379
TI  - BLASST: Band Limited Atomic Sampling With Spectral Tuning With Applications to
      Utility Line Noise Filtering.
AB  - OBJECTIVE: In this paper, we present and test a new method for the identification
      and removal of nonstationary utility line noise from biomedical signals. METHODS:
      The method, band limited atomic sampling with spectral tuning (BLASST), is an
      iterative approach that is designed to 1) fit nonstationarities in line noise by
      searching for best-fit Gabor atoms at predetermined time points, 2) self-modulate
      its fit by leveraging information from frequencies surrounding the target
      frequency, and 3) terminate based on a convergence criterion obtained from the
      same surrounding frequencies. To evaluate the performance of the proposed
      algorithm, we generate several simulated and real instances of nonstationary line
      noise and test BLASST along with alternative filtering approaches. RESULTS: We
      find that BLASST is capable of fitting line noise well and/or preserving local
      signal features relative to tested alternative filtering techniques. CONCLUSION:
      BLASST may present a useful alternative to bandpass, notch, or other filtering
      methods when experimentally relevant features have significant power in a
      spectrum that is contaminated by utility line noise, or when the line noise in
      question is highly nonstationary. SIGNIFICANCE: This is of particular
      significance in electroencephalography experiments, where line noise may be
      present in the frequency bands of neurological interest and measurements are
      typically of low enough strength that induced line noise can dominate the
      recorded signals. In conjunction with this paper, the authors have released a
      MATLAB toolbox that performs BLASST on real, vector-valued signals (available at
      https://github.com/VisLab/blasst).

PMID- 27893380
TI  - Area Determination of Diabetic Foot Ulcer Images Using a Cascaded Two-Stage SVM
      Based Classification.
AB  - The standard chronic wound assessment method based on visual examination is
      potentially inaccurate and also represents a significant clinical workload.
      Hence, computer-based systems providing quantitative wound assessment may be
      valuable for accurately monitoring wound healing status, with the wound area the
      best suited for automated analysis. Here, we present a novel approach, using
      support vector machines (SVM) to determine the wound boundaries on foot ulcer
      images captured with an image capture box, which provides controlled lighting and
      range. After superpixel segmentation, a cascaded two-stage classifier operates as
      follows: in the first stage, a set of k binary SVM classifiers are trained and
      applied to different subsets of the entire training images dataset, and
      incorrectly classified instances are collected. In the second stage, another
      binary SVM classifier is trained on the incorrectly classified set. We extracted
      various color and texture descriptors from superpixels that are used as input for
      each stage in the classifier training. Specifically, color and bag-of-word
      representations of local dense scale invariant feature transformation features
      are descriptors for ruling out irrelevant regions, and color and wavelet-based
      features are descriptors for distinguishing healthy tissue from wound regions.
      Finally, the detected wound boundary is refined by applying the conditional
      random field method. We have implemented the wound classification on a Nexus 5
      smartphone platform, except for training which was done offline. Results are
      compared with other classifiers and show that our approach provides high global
      performance rates (average sensitivity = 73.3%, specificity = 94.6%) and is
      sufficiently efficient for a smartphone-based image analysis.

PMID- 27893381
TI  - A Compressed Sensing Based Decomposition of Electrodermal Activity Signals.
AB  - The measurement and analysis of electrodermal activity (EDA) offers applications
      in diverse areas ranging from market research to seizure detection and to human
      stress analysis. Unfortunately, the analysis of EDA signals is made difficult by
      the superposition of numerous components that can obscure the signal information
      related to a user's response to a stimulus. We show how simple preprocessing
      followed by a novel compressed sensing based decomposition can mitigate the
      effects of the undesired noise components and help reveal the underlying
      physiological signal. The proposed framework allows for decomposition of EDA
      signals with provable bounds on the recovery of user responses. We test our
      procedure on both synthetic and real-world EDA signals from wearable sensors and
      demonstrate that our approach allows for more accurate recovery of user responses
      as compared with the existing techniques.

PMID- 27893382
TI  - A New Framework for Quality Assessment of High-Resolution Fingerprint Images.
AB  - The quality assessment of sets of features extracted from patterns of epidermal
      ridges on our fingers is a biometric challenge problem with implications on
      questions concerning security, privacy and identity fraud. In this work, we
      introduced a new methodology to analyze the quality of high-resolution
      fingerprint images containing sets of fingerprint pores. Our approach takes into
      account the spatial interrelationship between the considered features and some
      basic transformations involving point process and anisotropic analysis. We
      proposed two new quality index algorithms following spatial and structural
      classes of analysis. These algorithms have proved to be effective as a
      performance predictor and as a filter excluding low-quality features in a
      recognition process. The experiments using error reject curves show that the
      proposed approaches outperform the state-of-the-art quality assessment algorithm
      for high-resolution fingerprint recognition, besides defining a new method for
      reconstructing their friction ridge phases in a very consistent way.

PMID- 27893383
TI  - Efficient Globally Optimal Consensus Maximisation with Tree Search.
AB  - Maximum consensus is one of the most popular criteria for robust estimation in
      computer vision. Despite its widespread use, optimising the criterion is still
      customarily done by randomised sample-and-test techniques, which do not guarantee
      optimality of the result. Several globally optimal algorithms exist, but they are
      too slow to challenge the dominance of randomised methods. Our work aims to
      change this state of affairs by proposing an efficient algorithm for global
      maximisation of consensus. Under the framework of LP-type methods, we show how
      consensus maximisation for a wide variety of vision tasks can be posed as a tree
      search problem. This insight leads to a novel algorithm based on A* search. We
      propose efficient heuristic and support set updating routines that enable A*
      search to efficiently find globally optimal results. On common estimation
      problems, our algorithm is much faster than previous exact methods. Our work
      identifies a promising direction for globally optimal consensus maximisation.

PMID- 27893384
TI  - Recovering Inner Slices of Layered Translucent Objects by Multi-Frequency
      Illumination.
AB  - This paper describes a method for recovering appearance of inner slices of
      translucent objects. The appearance of a layered translucent object is the summed
      appearance of all layers, where each layer is blurred by a depth-dependent point
      spread function (PSF). By exploiting the difference of low-pass characteristics
      of depth-dependent PSFs, we develop a multi-frequency illumination method for
      obtaining the appearance of individual inner slices. Specifically, by observing
      the target object with varying the spatial frequency of checker-pattern
      illumination, our method recovers the appearance of inner slices via computation.
      We study the effect of non-uniform transmission due to inhomogeneity of
      translucent objects and develop a method for recovering clear inner slices based
      on the pixel-wise PSF estimates under the assumption of spatial smoothness of
      inner slice appearances. We quantitatively evaluate the accuracy of the proposed
      method by simulations and qualitatively show faithful recovery using real-world
      scenes.

PMID- 27893385
TI  - NELasso: Group-Sparse Modeling for Characterizing Relations Among Named Entities
      in News Articles.
AB  - Named entities such as people, locations, and organizations play a vital role in
      characterizing online content. They often reflect information of interest and are
      frequently used in search queries. Although named entities can be detected
      reliably from textual content, extracting relations among them is more
      challenging, yet useful in various applications (e.g., news recommending
      systems). In this paper, we present a novel model and system for learning
      semantic relations among named entities from collections of news articles. We
      model each named entity occurrence with sparse structured logistic regression,
      and consider the words (predictors) to be grouped based on background semantics.
      This sparse group LASSO approach forces the weights of word groups that do not
      influence the prediction towards zero. The resulting sparse structure is utilized
      for defining the type and strength of relations. Our unsupervised system yields a
      named entities' network where each relation is typed, quantified, and
      characterized in context. These relations are the key to understanding news
      material over time and customizing newsfeeds for readers. Extensive evaluation of
      our system on articles from TIME magazine and BBC News shows that the learned
      relations correlate with static semantic relatedness measures like WLM, and
      capture the evolving relationships among named entities over time.

PMID- 27893387
TI  - A CCA and ICA-Based Mixture Model for Identifying Major Depression Disorder.
AB  - The fMRI signals are usually filtered before processing and analyzing. This
      process can result in the loss of information carried by the higher frequency in
      the low frequency fluctuation. ICA and CCA are two classical methods in fMRI. ICA
      finds the statistically independent components of the observed data, however
      these components are usually physiologically uninterpretable without auxiliary
      procedures. CCA decomposes two sets of data into component pairs in some order,
      however these components may be mixtures of real signals and noise. In order to
      obtain statistically independent components and avoid the loss of information in
      the process of filtering, we propose a mixed model based on ICA and CCA, which
      does not need to filter the data. It is shown by the experiments that the new
      model has some advantages compared with the classical ICA and CCA. The components
      obtained by the new model is statistically independent. The useful information
      included in the low frequency fluctuation can be preserved. Experiments on
      synthetic data show satisfying results. As an application, this new model is used
      to design an algorithm to discriminate the major depressions from normal
      controls, with encouraging experimental results.

PMID- 27893388
TI  - Sparse Representation-Based Multiple Frame Video Super-Resolution.
AB  - In this paper, we propose two multiple-frame super-resolution (SR) algorithms
      based on dictionary learning (DL) and motion estimation. First, we adopt the use
      of video bilevel DL, which has been used for single-frame SR. It is extended to
      multiple frames by using motion estimation with sub-pixel accuracy. We propose a
      batch and a temporally recursive multi-frame SR algorithm, which improves over
      single-frame SR. Finally, we propose a novel DL algorithm utilizing consecutive
      video frames, rather than still images or individual video frames, which further
      improves the performance of the video SR algorithms. Extensive experimental
      comparisons with the state-of-the-art SR algorithms verify the effectiveness of
      our proposed multiple-frame video SR approach.

PMID- 27893386
TI  - Optimizing MR Scan Design for Model-Based ${T}_{1}$ , ${T}_{2}$ Estimation From
      Steady-State Sequences.
AB  - Rapid, reliable quantification of MR relaxation parameters T1 and T2 is desirable
      for many clinical applications. Steady-state sequences such as Spoiled Gradient
      Recalled Echo (SPGR) and Dual-Echo Steady-State (DESS) are fast and well-suited
      for relaxometry because the signals they produce are quite sensitive to T1 and T2
      variation. However, T1, T2 estimation with these sequences typically requires
      multiple scans with varied sets of acquisition parameters. This paper describes a
      systematic framework for selecting scan types (e.g., combinations of SPGR and
      DESS scans) and optimizing their respective parameters (e.g., flip angles and
      repetition times). The method is based on a Cramer-Rao Bound (CRB)-inspired min
      max optimization that finds scan parameter combinations that robustly enable
      precise object parameter estimation. We apply this technique to optimize
      combinations of SPGR and DESS scans for T1, T2 relaxometry in white matter (WM)
      and grey matter (GM) regions of the human brain at 3T field strength. Phantom
      accuracy experiments show that SPGR/DESS scan combinations are in excellent
      agreement with reference measurements. Phantom precision experiments show that
      trends in T1,T2 pooled sample standard deviations reflect CRB-based predictions.
      In vivo experiments show that in WM and GM, T1 and T2 estimates from a pair of
      optimized DESS scans exhibit precision (but not necessarily accuracy) comparable
      to that of optimized combinations of SPGR and DESS scans. To our knowledge, T1
      maps from DESS acquisitions alone are new. This example application illustrates
      that scan optimization may help reveal new parameter mapping techniques from
      combinations of established pulse sequences.

PMID- 27893389
TI  - Joint Defogging and Demosaicking.
AB  - Image defogging is a technique used extensively for enhancing visual quality of
      images in bad weather conditions. Even though defogging algorithms have been well
      studied, defogging performance is degraded by demosaicking artifacts and sensor
      noise amplification in distant scenes. In order to improve the visual quality of
      restored images, we propose a novel approach to perform defogging and
      demosaicking simultaneously. We conclude that better defogging performance with
      fewer artifacts can be achieved when a defogging algorithm is combined with a
      demosaicking algorithm simultaneously. We also demonstrate that the proposed
      joint algorithm has the benefit of suppressing noise amplification in distant
      scenes. In addition, we validate our theoretical analysis and observations for
      both synthesized data sets with ground truth fog-free images and natural scene
      data sets captured in a raw format.

PMID- 27893391
TI  - Robust Transfer Metric Learning for Image Classification.
AB  - Metric learning has attracted increasing attention due to its critical role in
      image analysis and classification. Conventional metric learning always assumes
      that the training and test data are sampled from the same or similar
      distribution. However, to build an effective distance metric, we need abundant
      supervised knowledge (i.e., side/label information), which is generally
      inaccessible in practice, because of the expensive labeling cost. In this paper,
      we develop a robust transfer metric learning (RTML) framework to effectively
      assist the unlabeled target learning by transferring the knowledge from the well
      labeled source domain. Specifically, RTML exploits knowledge transfer to mitigate
      the domain shift in two directions, i.e., sample space and feature space. In the
      sample space, domain-wise and class-wise adaption schemes are adopted to bridge
      the gap of marginal and conditional distribution disparities across two domains.
      In the feature space, our metric is built in a marginalized denoising fashion and
      low-rank constraint, which make it more robust to tackle noisy data in reality.
      Furthermore, we design an explicit rank constraint regularizer to replace the
      rank minimization NP-hard problem to guide the low-rank metric learning.
      Experimental results on several standard benchmarks demonstrate the effectiveness
      of our proposed RTML by comparing it with the state-of-the-art transfer learning
      and metric learning algorithms.

PMID- 27893392
TI  - Waterloo Exploration Database: New Challenges for Image Quality Assessment
      Models.
AB  - The great content diversity of real-world digital images poses a grand challenge
      to image quality assessment (IQA) models, which are traditionally designed and
      validated on a handful of commonly used IQA databases with very limited content
      variation. To test the generalization capability and to facilitate the wide usage
      of IQA techniques in real-world applications, we establish a large-scale database
      named the Waterloo Exploration Database, which in its current state contains 4744
      pristine natural images and 94 880 distorted images created from them. Instead of
      collecting the mean opinion score for each image via subjective testing, which is
      extremely difficult if not impossible, we present three alternative test criteria
      to evaluate the performance of IQA models, namely, the pristine/distorted image
      discriminability test, the listwise ranking consistency test, and the pairwise
      preference consistency test (P-test). We compare 20 well-known IQA models using
      the proposed criteria, which not only provide a stronger test in a more
      challenging testing environment for existing models, but also demonstrate the
      additional benefits of using the proposed database. For example, in the P-test,
      even for the best performing no-reference IQA model, more than 6 million failure
      cases against the model are "discovered" automatically out of over 1 billion test
      pairs. Furthermore, we discuss how the new database may be exploited using
      innovative approaches in the future, to reveal the weaknesses of existing IQA
      models, to provide insights on how to improve the models, and to shed light on
      how the next-generation IQA models may be developed. The database and codes are
      made publicly available at: https://ece.uwaterloo.ca/~k29ma/exploration/.

PMID- 27893393
TI  - Salient object detection with spatiotemporal background priors for video.
AB  - Saliency detection for images has been studied for many years, for which a lot of
      methods have been designed. In saliency detection, background priors which are
      often regarded as pseudo-background are effective clues to find salient objects
      in images. Although image boundary is commonly used background priors, it doesn't
      work well for images of complex scenes and videos. In this paper, we explore how
      to identify the background priors for a video and propose a saliency based method
      to detect the visual objects by using background priors. For a video, we
      integrate multiple pairs of SIFT flows from long-range frames and a bidirectional
      consistency propagation is conducted to obtain the accurate and sufficient
      temporal background priors, which are combined with spatial background priors to
      generate spatiotemporal background priors. Next, a novel dual-graph based
      structure using spatiotemporal background priors is put forward in computation of
      saliency maps, fully taking advantage of appearance and motion information in
      videos. Experimental results on different challenging datasets show that the
      proposed method robustly and accurately detect the video objects in both simple
      and complex scenes and achieve better performance compared with other state-of
      the-art video saliency models.

PMID- 27893394
TI  - A Robust and Efficient Approach to License Plate Detection.
AB  - This paper presents a robust and efficient method for license plate detection
      with the purpose of accurately localizing vehicle license plates from complex
      scenes in real time. A simple yet effective image downscaling method is first
      proposed to substantially accelerate license plate localization without
      sacrificing detection performance compared with that achieved using the original
      image. Furthermore, a novel line density filter approach is proposed to extract
      candidate regions, thereby significantly reducing the area to be analyzed for
      license plate localization. Moreover, a cascaded license plate classifier based
      on linear support vector machines using color saliency features is introduced to
      identify the true license plate from among the candidate regions. For performance
      evaluation, a data set consisting of 3977 images captured from diverse scenes
      under different conditions is also presented. Extensive experiments on the widely
      used Caltech license plate data set and our newly introduced data set demonstrate
      that the proposed approach substantially outperforms state-of-the-art methods in
      terms of both detection accuracy and run-time efficiency, increasing the
      detection ratio from 91.09% to 96.62% while decreasing the run time from 672 to
      42 ms for processing an image with a resolution of 1082*728 . The executable code
      and our collected data set are publicly available.

PMID- 27893395
TI  - Fast Physically Correct Refocusing for Sparse Light Fields Using Block-Based
      Multi-Rate View Interpolation.
AB  - Digital refocusing has a tradeoff between complexity and quality when using
      sparsely sampled light fields for low-storage applications. In this paper, we
      propose a fast physically correct refocusing algorithm to address this issue in a
      twofold way. First, view interpolation is adopted to provide photorealistic
      quality at infocus-defocus hybrid boundaries. Regarding its conventional high
      complexity, we devised a fast line-scan method specifically for refocusing, and
      its 1D kernel can be 30* faster than the benchmark View Synthesis Reference
      Software (VSRS)-1D-Fast. Second, we propose a block-based multi-rate processing
      flow for accelerating purely infocused or defocused regions, and a further 3- 34*
      speedup can be achieved for high-resolution images. All candidate blocks of
      variable sizes can interpolate different numbers of rendered views and perform
      refocusing in different subsampled layers. To avoid visible aliasing and block
      artifacts, we determine these parameters and the simulated aperture filter
      through a localized filter response analysis using defocus blur statistics. The
      final quadtree block partitions are then optimized in terms of computation time.
      Extensive experimental results are provided to show superior refocusing quality
      and fast computation speed. In particular, the run time is comparable with the
      conventional single-image blurring, which causes serious boundary artifacts.

PMID- 27893398
TI  - Probabilistic Inference on Multiple Normalized Genome-Wide Signal Profiles With
      Model Regularization.
AB  - Understanding genome-wide protein-DNA interaction signals forms the basis for
      further focused studies in gene regulation. In particular, the chromatin
      immunoprecipitation with massively parallel DNA sequencing technology (ChIP-Seq)
      can enable us to measure the in vivo genome-wide occupancy of the DNA-binding
      protein of interest in a single run. Multiple ChIP-Seq runs thus inherent the
      potential for us to decipher the combinatorial occupancies of multiple DNA
      binding proteins. To handle the genome-wide signal profiles from those multiple
      runs, we propose to integrate regularized regression functions (i.e., LASSO,
      Elastic Net, and Ridge Regression) into the well-established SignalRanker and
      FullSignalRanker frameworks, resulting in six additional probabilistic models for
      inference on multiple normalized genome-wide signal profiles. The corresponding
      model training algorithms are devised with computational complexity analysis.
      Comprehensive benchmarking is conducted to demonstrate and compare the
      performance of nine related probabilistic models on the ENCODE ChIP-Seq datasets.
      The results indicate that the regularized SignalRanker models, in contrast to the
      original SignalRanker models, can demonstrate excellent inference performance
      comparable to the FullSignalRanker models with low model complexities and time
      complexities. Such a feature is especially valuable in the context of the rapidly
      growing genome-wide signal profile data in the recent years.

PMID- 27893397
TI  - Capacity and Delay Spread in Multilayer Diffusion-Based Molecular Communication
      (DBMC) Channel.
AB  - In nanoscale communication, diffusion-based molecular communication (DBMC) in
      which information is encoded into molecule patterns by a transmitter nanomachine,
      has emerged as a promising communication system, particularly for biomedical and
      healthcare applications. Although, numerous studies have been conducted to
      evaluate and analyze DBMC systems, investigation on DBMC system through a
      multilayer channel has received less attention. The aims of this paper are to
      formulate channel characteristics and to evaluate the performance of multilayer
      DBMC channel in terms of delay spread and capacity. In this paper, the
      propagation of molecules over an n- layer channel is assumed to follow the
      Brownian motion and subjected to Fick's law of diffusion. Fourier transform is
      used to convert time to frequency domain functions. Besides, the multilayer
      channel is considered as a linear and deterministic channel. For the performance
      evaluation, the air-water-blood plasma medium representing the simplified
      multilayer diffusion model in the respiratory system was chosen. It was found
      that a high channel capacity can be achieved with wide transmission bandwidth,
      short transmission distance, and high averaged transmitted power. In addition,
      the findings showed that channel delay spread increases as both the transmission
      distance, and the pulse duration increased. By setting the symbol duration
      greater than the pulse duration or delay spread, an inter-symbol interference
      problem due to previous molecules transmission can be mitigated. These findings
      can be used as a guide in the development and fabrication of future artificial
      nanocommunication and nanonetworks systems involving multilayer transmission
      medium.

PMID- 27893396
TI  - Enhanced Control of Cortical Pyramidal Neurons With Micromagnetic Stimulation.
AB  - Magnetic stimulation is less sensitive to the inflammatory reactions that plague
      conventional electrode-based cortical implants and therefore may be useful as a
      next-generation (implanted) cortical prosthetic. The fields arising from micro
      coils are quite small however and thus, their ability to modulate cortical
      activity must first be established. Here, we show that layer V pyramidal neurons
      (PNs) can be strongly activated by micro-coil stimulation and further, the
      asymmetric fields arising from such coils do not simultaneously activate
      horizontally-oriented axon fibers, thus confining activation to a focal region
      around the coil. The spatially-narrow fields from micro-coils allowed the
      sensitivity of different regions within a single PN to be compared: while the
      proximal axon was most sensitive in naive cells, repetitive stimulation over the
      apical dendrite led to a change in state of the neuron that reduced thresholds
      there to below those of the axon. Thus, our results raise the possibility that
      regardless of the mode of stimulation, penetration depths that target specific
      portions of the apical dendrite may actually be more effective than those that
      target Layer 6. Interestingly, the state change had similar properties to state
      changes described previously at the systems level, suggesting a possible neuronal
      mechanism underlying such responses.

PMID- 27893400
TI  - Multivariate Cryptography Based on Clipped Hopfield Neural Network.
AB  - Designing secure and efficient multivariate public key cryptosystems
      [multivariate cryptography (MVC)] to strengthen the security of RSA and ECC in
      conventional and quantum computational environment continues to be a challenging
      research in recent years. In this paper, we will describe multivariate public key
      cryptosystems based on extended Clipped Hopfield Neural Network (CHNN) and
      implement it using the MVC (CHNN-MVC) framework operated in space. The Diffie
      Hellman key exchange algorithm is extended into the matrix field, which
      illustrates the feasibility of its new applications in both classic and
      postquantum cryptography. The efficiency and security of our proposed new public
      key cryptosystem CHNN-MVC are simulated and found to be NP-hard. The proposed
      algorithm will strengthen multivariate public key cryptosystems and allows
      hardware realization practicality.

PMID- 27893401
TI  - Heartbeat Classification Using Abstract Features From the Abductive
      Interpretation of the ECG.
AB  - OBJECTIVE: This paper aims to prove that automatic beat classification on ECG
      signals can be effectively solved with a pure knowledge-based approach, using an
      appropriate set of abstract features obtained from the interpretation of the
      physiological processes underlying the signal. METHODS: A set of qualitative
      morphological and rhythm features are obtained for each heartbeat as a result of
      the abductive interpretation of the ECG. Then, a QRS clustering algorithm is
      applied in order to reduce the effect of possible errors in the interpretation.
      Finally, a rule-based classifier assigns a tag to each cluster. RESULTS: The
      method has been tested with the MIT-BIH Arrhythmia Database records, showing a
      significantly better performance than any other automatic approach in the state
      of-the-art, and even improving most of the assisted approaches that require the
      intervention of an expert in the process. CONCLUSION: The most relevant issues in
      ECG classification, related to a large extent to the variability of the signal
      patterns between different subjects and even in the same subject over time, will
      be overcome by changing the reasoning paradigm. SIGNIFICANCE: This paper
      demonstrates the power of an abductive framework for time-series interpretation
      to make a qualitative leap in the significance of the information extracted from
      the ECG by automatic methods.

PMID- 27893403
TI  - Real-Time Robust Heart Rate Estimation From Wrist-Type PPG Signals Using Multiple
      Reference Adaptive Noise Cancellation.
AB  - Heart rate (HR) monitoring using photoplethysmographic (PPG) signals recorded
      from wearers' wrist greatly facilitates design of wearable devices and maximizes
      user experience. However, placing PPG sensors in wrist causes much stronger and
      complicated motion artifacts (MA) due to loose interface between sensors and
      skin. Therefore, developing robust HR estimation algorithms for wrist-type PPG
      signals has significant commercial values. In this paper, we propose a robust HR
      estimation algorithm for wrist-type PPG signals using multiple reference adaptive
      noise cancellation (ANC) technique-termed here as "MURAD." The main challenge of
      using ANC for MA reduction is to devise a qualified reference noise signal (RNS)
      to the adaptive filter. We propose a novel solution by using four RNSs, namely,
      the three-axis accelerometer data and the difference signal between the two PPG
      signals. For each RNS, we get a different version of the cleaned PPG signal.
      Then, a set of probable HR values is estimated using all of the cleaned PPG
      signals, and then, the value that is closest to the estimated HR of the previous
      time window is chosen to be the HR estimate of the current window. Then, some
      peak verification techniques are employed to ensure accurate HR estimations. The
      proposed technique gives lower average absolute error compared to state-of-the
      art methods. So, MURAD method provides a promising solution to the challenge of
      HR monitoring using PPG in wearable devices during severe MA conditions.

PMID- 27893404
TI  - Policy Gradient Adaptive Dynamic Programming for Data-Based Optimal Control.
AB  - The model-free optimal control problem of general discrete-time nonlinear systems
      is considered in this paper, and a data-based policy gradient adaptive dynamic
      programming (PGADP) algorithm is developed to design an adaptive optimal
      controller method. By using offline and online data rather than the mathematical
      system model, the PGADP algorithm improves control policy with a gradient descent
      scheme. The convergence of the PGADP algorithm is proved by demonstrating that
      the constructed Q -function sequence converges to the optimal Q -function. Based
      on the PGADP algorithm, the adaptive control method is developed with an actor
      critic structure and the method of weighted residuals. Its convergence properties
      are analyzed, where the approximate Q -function converges to its optimum.
      Computer simulation results demonstrate the effectiveness of the PGADP-based
      adaptive control method.

PMID- 27893402
TI  - A Convolutional Neural Network for Automatic Characterization of Plaque
      Composition in Carotid Ultrasound.
AB  - Characterization of carotid plaque composition, more specifically the amount of
      lipid core, fibrous tissue, and calcified tissue, is an important task for the
      identification of plaques that are prone to rupture, and thus for early risk
      estimation of cardiovascular and cerebrovascular events. Due to its low costs and
      wide availability, carotid ultrasound has the potential to become the modality of
      choice for plaque characterization in clinical practice. However, its significant
      image noise, coupled with the small size of the plaques and their complex
      appearance, makes it difficult for automated techniques to discriminate between
      the different plaque constituents. In this paper, we propose to address this
      challenging problem by exploiting the unique capabilities of the emerging deep
      learning framework. More specifically, and unlike existing works which require a
      priori definition of specific imaging features or thresholding values, we propose
      to build a convolutional neural network (CNN) that will automatically extract
      from the images the information that is optimal for the identification of the
      different plaque constituents. We used approximately 90 000 patches extracted
      from a database of images and corresponding expert plaque characterizations to
      train and to validate the proposed CNN. The results of cross-validation
      experiments show a correlation of about 0.90 with the clinical assessment for the
      estimation of lipid core, fibrous cap, and calcified tissue areas, indicating the
      potential of deep learning for the challenging task of automatic characterization
      of plaque composition in carotid ultrasound.

PMID- 27893405
TI  - Second-Order Consensus in Multiagent Systems via Distributed Sliding Mode
      Control.
AB  - In this paper, the new decoupled distributed sliding-mode control (DSMC) is first
      proposed for second-order consensus in multiagent systems, which finally solves
      the fundamental unknown problem for sliding-mode control (SMC) design of coupled
      networked systems. A distributed full-order sliding-mode surface is designed
      based on the homogeneity with dilation for reaching second-order consensus in
      multiagent systems, under which the sliding-mode states are decoupled. Then, the
      SMC is applied to the decoupled sliding-mode states to reach their origin in
      finite time, which is the sliding-mode surface. The states of agents can first
      reach the designed sliding-mode surface in finite time and then move to the
      second-order consensus state along the surface in finite time as well. The DSMC
      designed in this paper can eliminate the influence of singularity problems and
      weaken the influence of chattering, which is still very difficult in the SMC
      systems. In addition, DSMC proposes a general decoupling framework for designing
      SMC in networked multiagent systems. Simulations are presented to verify the
      theoretical results in this paper.

PMID- 27893406
TI  - Adaptive Granulation-Based Prediction for Energy System of Steel Industry.
AB  - The flow variation tendency of byproduct gas plays a crucial role for energy
      scheduling in steel industry. An accurate prediction of its future trends will be
      significantly beneficial for the economic profits of steel enterprise. In this
      paper, a long-term prediction model for the energy system is proposed by
      providing an adaptive granulation-based method that considers the production
      semantics involved in the fluctuation tendency of the energy data, and partitions
      them into a series of information granules. To fully reflect the corresponding
      data characteristics of the formed unequal-length temporal granules, a 3-D
      feature space consisting of the timespan, the amplitude and the linetype is
      designed as linguistic descriptors. In particular, a collaborative-conditional
      fuzzy clustering method is proposed to granularize the tendency-based feature
      descriptors and specifically measure the amplitude variation of industrial data
      which plays a dominant role in the feature space. To quantify the performance of
      the proposed method, a series of real-world industrial data coming from the
      energy data center of a steel plant is employed to conduct the comparative
      experiments. The experimental results demonstrate that the proposed method
      successively satisfies the requirements of the practically viable prediction.

PMID- 27893407
TI  - Decentralized Fault Tolerant Control for a Class of Interconnected Nonlinear
      Systems.
AB  - This paper proposes a decentralized fault tolerant methodology for a class of
      interconnected nonlinear systems. The key novelty of our proposed method is that
      fault tolerant control can be achieved without necessarily exchanging the state
      information between the subsystems and the couplings' effect can be dealt with
      utilizing the cyclic-small-gain methodology. Simulation results demonstrate
      effectively the validity of our proposed approach.

PMID- 27893408
TI  - Betweenness Centrality-Based Consensus Protocol for Second-Order Multiagent
      Systems With Sampled-Data.
AB  - This paper designs a new leader-following consensus protocol for second-order
      multiagent systems with time-varying sampling. For the first time in designing a
      leader-following protocol, the concept of betweenness centrality is adopted to
      analyze the information flow in the consensus problem for multiagent systems. By
      construction of a suitable Lyapunov-Krasovskii functional, some criteria for
      designing consensus protocols of such systems are established in terms of linear
      matrix inequalities which can be easily solved by various effective optimization
      algorithms. One numerical example is given to illustrate the validity of the
      proposed argument.

PMID- 27893409
TI  - Strategies for improvement of WeChat-PBL teaching: experience from China.

PMID- 27893410
TI  - Characterization of variations in IL23A and IL23R genes: possible roles in
      multiple sclerosis and other neuroinflammatory demyelinating diseases.
AB  - Multiple sclerosis is among the most serious inflammatory demyelinating diseases
      (IDD). Interleukin-23A (IL23A) regulates and coordinates the activities of immune
      cells by interacting with its receptor IL23R and plays key roles in the
      pathogenesis of immune inflammatory diseases. IDD, deemed to be a kind of
      autoimmune diseases, may involve IL23A in the pathogenesis. The aim of this work
      was to validate the hypothesized involvement of IL-23A and its receptor in IDD.
      We sequenced the IL-23A and IL-23R genes for 206 Chinese Han IDD patients and
      evaluated SNPs within or near those genes. The serum levels of IL23A in IDD
      participants were analyzed using ELISA. The statistical analyses were conducted
      using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg
      equilibrium test of the population was carried out using online software OEGE.
      Three variants rs2066808, rs2371494, rs11575248 in IL-23A gene and one variant
      rs1884444 in IL-23R gene were demonstrated to be associated with the risk of MS
      or other IDD diseases, and the expression level of serum IL-23A in the MS
      patients was also altered. We conclude that variants in IL-23A and IL-23R genes
      were associated with the risk of MS or other IDD diseases.

PMID- 27893411
TI  - Plasma osteoprotegerin and breast cancer risk in BRCA1 and BRCA2 mutation
      carriers.
AB  - Emerging evidence suggests a role of receptor activator of nuclear factor kappaB
      (RANK)/RANK ligand (RANKL) signaling in breast cancer development. Lower
      osteoprotegerin (OPG) levels, the endogenous decoy receptor for RANKL which
      competes with RANK for binding of RANKL, has been reported among BRCA mutation
      carriers. Whether low OPG levels contribute to the high breast cancer risk in
      this population is unknown. OPG concentrations were measured in plasma of 206
      cancer-free BRCA mutation carriers using an enzyme-linked immunosorbent assay.
      Subjects were categorized as high vs. low based on the median of the entire
      cohort (95 ng/mL) and followed for a new diagnosis of breast cancer. Cumulative
      incidence by baseline plasma OPG concentration was estimated using Kaplan-Meier
      survival analysis. Cox proportional hazards models were used to estimate the
      adjusted hazard ratios for the association between plasma OPG and breast cancer
      risk. Over a mean follow-up period of 6.5 years (range 0.1-18.8 years), 18
      incident breast cancer cases were observed. After ten years of follow-up, the
      cumulative incidence of breast cancer among women with low OPG was 21%, compared
      to 9% among women with high OPG (P-log rank = 0.046). After multivariate
      adjustment, women with high plasma OPG had a significantly decreased risk of
      developing breast cancer, compared to women with low OPG (HR = 0.25; 95%CI 0.08
      0.78; P = 0.02). These data suggest that low OPG levels are associated with an
      increased risk of BRCA-associated breast cancer. Targeting RANK signalling may
      represent a plausible, non-surgical prevention option for BRCA mutation carriers.

PMID- 27893412
TI  - Molecular mechanism and therapeutic implications of selinexor (KPT-330) in
      liposarcoma.
AB  - Exportin-1 mediates nuclear export of multiple tumor suppressor and growth
      regulatory proteins. Aberrant expression of exportin-1 is noted in human
      malignancies, resulting in cytoplasmic mislocalization of its target proteins. We
      investigated the efficacy of selinexor against liposarcoma cells both in vitro
      and in vivo. Exportin-1 was highly expressed in liposarcoma samples and cell
      lines as determined by immunohistochemistry, western blot, and immunofluorescence
      assay. Knockdown of endogenous exportin-1 inhibited proliferation of liposarcoma
      cells. Selinexor also significantly decreased cell proliferation as well as
      induced cell cycle arrest and apoptosis of liposarcoma cells. The drug also
      significantly decreased tumor volumes and weights of liposarcoma xenografts.
      Importantly, selinexor inhibited insulin-like growth factor 1 (IGF1) activation
      of IGF-1R/AKT pathway through upregulation of insulin-like growth factor binding
      protein 5 (IGFBP5). Further, overexpression and knockdown experiments showed that
      IGFBP5 acts as a tumor suppressor and its expression was restored upon selinexor
      treatment of liposarcoma cells. Selinexor decreased aurora kinase A and B levels
      in these cells and inhibitors of these kinases suppressed the growth of the
      liposarcoma cells. Overall, our study showed that selinexor treatment restored
      tumor suppressive function of IGFBP5 and inhibited aurora kinase A and B in
      liposarcoma cells supporting the usefulness of selinexor as a potential
      therapeutic strategy for the treatment of this cancer.

PMID- 27893413
TI  - KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression in non-small cell lung
      cancer.
AB  - BACKGROUND: Nature killer (NK) cells are the immune system's first line of
      defense against both viral infections and tumors. Killer cell immunoglobulin-like
      receptors (KIRs) are associated with susceptibility to different types of
      cancers. We investigated KIR 2D (L1, L3, L4, S4) and KIR 3DL1 protein expression
      and their association with survival in non-small cell lung cancer (NSCLC).
      METHODS: The expression of KIR 2D (L1, L3, L4, S4) (BC032422/ ADQ31987/
      NP_002246/ NP_036446, ABCAM) and KIR 3DL1 (AA 1-444, ABCAM) protein was assessed
      by immunohistochemistry (IHC) in 62 NSCLC patients. RESULTS: KIR 2D (L1, L3, L4,
      S4) and KIR 3DL1 were expressed both on NSCLC tumor cells and tumor infiltrating
      lymphocytes (TILs). Fourteen samples (22.6%) stained positive for KIR 2D (L1, L3,
      L4, S4) on the tumor cells, and 10 (16.1%) had positive expression on the TILs.
      Thirty-three samples (53.2%) stained positive for KIR 3DL1 on the tumor cells,
      and 31 (50.0%) had positive expression on the TILs. Patients with negative KIR 2D
      (L1, L3, L4, S4) expression on tumor cells or TILs had longer overall survival
      (OS) than patients who are KIR 2D (L1, L3, L4, S4) positive on tumor cells (40.70
      weeks, 95% CI 24.76-56.65 vs. 7.10 weeks, 95% CI 0.00-19.38, P = 0.014) or TILs
      (40.70 weeks, 95% CI 24.05-57.35 vs. 3.90 weeks, 95% CI 0.00-9.17, P < 0.001).
      Likewise, longer OS was significantly correlated with negative expression of KIR
      3DL1 on tumor cells (62.30 weeks, 95% CI 0.00-177.37 vs. 13.10 weeks, 95% CI 3.42
      22.78, P < 0.001) or TILs (62.30 weeks, 95% CI 0.00-152.05 vs. 12.10 weeks, 95%
      CI 2.61-21.59, P < 0.001). Cox regression analysis showed that KIR 2D (L1, L3,
      L4, S4) on TILs was correlated with OS (P = 0.032, Odds Ratio 2.628 95%CI 1.089
      6.340). CONCLUSIONS: KIR 2D (L1, L3, L4, S4) and KIR 3DL1 expression was
      correlated with poor prognosis in NSCLC patients.

PMID- 27893414
TI  - Recombinant Haemonchus contortus 24 kDa excretory/secretory protein (rHcES-24)
      modulate the immune functions of goat PBMCs in vitro.
AB  - A 24 kDa protein is one of the important components in Haemonchus contortus
      (barber pole worm) excretory/secretory products (HcESPs), which was shown to have
      important antigenic function. However, little is known about the immunomodulatory
      effects of this proteinon host cell. In the present study gene encoding 24kDa
      excretory/secretory protein (HcES-24) was cloned. The recombinant protein of HcES
      24 (rHcES-24) was expressed in a histidine-tagged fusion protein soluble form in
      Escherichia coli. Binding activity of rHcES-24 to goat PBMCs was confirmed by
      immunofluorescence assay (IFA) and its immunomudulatory effect on cytokine
      secretion, cell proliferation, cell migration and nitric oxide production were
      observed by co-incubation of rHcES-24. IFA results revealed that rHcES-24 could
      bind to the PBMCs. The interaction of rHcES-24 increased the production of IL4,
      IL10, IL17 and cell migration in dose dependent manner. However, rHcES-24
      treatment significantly suppressed the production of IFNgamma, proliferation of
      the PBMC and Nitric oxide (NO) production. Our findings showed that the rHcES-24
      played important regulatory effects on the goat PBMCs.

PMID- 27893415
TI  - Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease
      severity and response to therapy in children given haematopoietic stem cell
      transplantation.
AB  - Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic
      haematopoietic stem cell transplantation, with a significant proportion of
      patients failing to respond to first-line systemic corticosteroids. Reliable
      biomarkers predicting disease severity and response to treatment are warranted to
      improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3),
      an acute-phase protein produced locally at the site of inflammation, could
      represent a novel acute GvHD biomarker. Using a murine model of the disease, we
      found increased PTX3 plasma levels after irradiation and at GvHD onset.
      Similarly, plasma PTX3 was enhanced in 115 pediatric patients on day of
      transplantation, likely due to conditioning, and at GvHD onset in patients
      experiencing clinical symptoms of the disease. PTX3 was also found increased in
      skin and colon biopsies from patients with active disease. Furthermore, PTX3
      plasma levels at GvHD onset were predictive of disease outcome since they
      resulted significantly higher in both severe and therapy-unresponsive patients.
      Multiple injections of rhPTX3 in the murine model of GvHD did not influence the
      disease course. Taken together, our results indicate that PTX3 constitutes a
      biomarker of GvHD severity and therapy response useful to tailor treatment
      intensity according to early risk-stratification of GvHD patients.

PMID- 27893416
TI  - The effect of FcgammaRIIA and FcgammaRIIB on coronary artery lesion formation and
      intravenous immunoglobulin treatment responses in children with Kawasaki disease.
AB  - Previous research has found patients with the FcgammaRIIIB NA1 variant having
      increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki
      disease (KD). Our previous studies revealed that elevated FcgammaRIIA expression
      correlated with the susceptibility of KD patients. We conducted this research to
      determine whether and how Fcgamma receptors affect the susceptibility, IVIG
      treatment response, and coronary artery lesions (CAL) of KD patients. The
      activating FcgammaRIIA and inhibitory FcgammaRIIB methylation levels of seven
      patients with KD and four control subjects were examined using HumanMethylation27
      BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with
      fevers. We performed real-time RT-PCR to determine the FcgammaRIIA and
      FcgammaRIIB expression levels, as well as a luciferase assay of FcgammaRIIA. We
      found a considerable increase in methylation of both FcgammaRIIA and FcgammaRIIB
      in KD patients undergoing IVIG treatment. Promoter methylation of FcgammaRIIA
      inhibited reporter activity in K562 cells using luciferase assay. The FcgammaRIIB
      mRNA expression levels were not found to increase susceptibility, CAL formation,
      or IVIG resistance. FcgammaRIIA mRNA expression levels were significantly higher
      in IVIG-resistant patients than in those that responded to IVIG during the pre
      treatment period. Furthermore, the FcgammaRIIA/IIB mRNA expression ratio was
      considerably higher in KD patients with CAL than in those without CAL.
      FcgammaRIIA and FcgammaRIIB both demonstrated increased methylation levels in KD
      patients that underwent IVIG treatment. FcgammaRIIA expression influenced the
      IVIG treatment response of KD patients. The FcgammaRIIA/IIB mRNA expression ratio
      was greater in KD patients with CAL formation.

PMID- 27893417
TI  - Genetic and epigenetic silencing of mircoRNA-506-3p enhances COTL1 oncogene
      expression to foster non-small lung cancer progression.
AB  - Although previous studies suggested that microRNA-506-3p (miR-506-3p) was
      frequently downregulated, and functioned as a tumor suppressor in several
      cancers, the biological role and intrinsic regulatory mechanisms of miR-506-3p in
      non-small cell lung cancer (NSCLC) remain elusive. The present study found miR
      506-3p expression was downregulated in advanced NSCLC tissues and cell lines. The
      expression of miR-506-3p in NSCLC was inversely correlated with larger tumor
      size, advanced TNM stage and lymph node metastasis. In addition, we also found
      patients with lower expression of miR-506-3p had a poor prognosis than those
      patients with higher expression of miR-506-3p. Function studies demonstrated that
      aberrant miR-506-3p expression modulates tumor cell growth, cell mobility, cell
      migration and invasion in vitro and in vivo. Mechanistic investigations
      manifested that coactosin-like protein 1 (COTL1) was a direct downstream target
      of miR-506-3p. Knockdown of COTL1 mimicked the tumor-suppressive effects of miR
      506-3p overexpression in A549 cells, whereas COTL1 overexpression enhanced the
      tumorigenic function in HCC827 cells. Importantly, we also found GATA3
      transcriptionally actives miR-506-3p expression, and the long non-coding RNA
      urothelial carcinoma-associated 1 (UCA1) exerts oncogenic function in NSCLC by
      competitively 'sponging' miRNA-506. Together, our combined results elucidated
      genetic and epigenetic silencing of miR-506-3p enhances COTL1 oncogene expression
      to foster NSCLC progression.

PMID- 27893418
TI  - High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck
      squamous cell carcinoma patients in Singapore.
AB  - Human papillomavirus (HPV), especially HPV16 genotype, is associated with
      oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence
      and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in
      a South-East Asian multi-ethnic society in Singapore and examine its prognostic
      significance.159 HNSCC archival tissue samples were retrieved and tumour DNA was
      screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV
      genotyping RH test). P16 protein overexpression was identified using
      immunohistochemistry (IHC). Statistical correlation between clinical outcomes
      were performed between HPV-positive and negative HNSCC patients.Six HR-HPVs
      (HPV16, 18, 31, 45, 56, 68) were detected in 90.6% of HNSCC; and 79.9% had
      multiple HPV genotypes detected. HPV31 and HPV45 were the most prevalent (79.2%
      and 87.4%, respectively); and HPV16 was predominantly found in OPSCC (p < 0.001).
      HPV-DNA PCR assay yielded a high sensitivity (96%) but low specificity (11%) when
      compared to p16 immunohistochemistry as the reference standard.P16-positive HNSCC
      was predominantly observed in OPSCC (73.7%; p = 0.005); and p16-positive OPSCC
      exhibited improved overall survival compared to p16-negative OPSCC (p = 0.022).
      Similarly, smoking and alcohol consumption were poor prognostic factors of
      overall survival (p = 0.007; p = 0.01) in OPSCC patients.HR-HPVs were identified
      in 90.6% of HNSCC patients using the HPV-DNA PCR assay. This test had a poor
      specificity when compared to p16 IHC; making it an unreliable detection technique
      in selecting patients for radiation dose de-escalation treatment protocol. P16
      positive tumor was predominantly found in the oropharynx these patients
      demonstrated better overall survival than those with p16-negative OPSCC.

PMID- 27893419
TI  - Silver nanoparticles enhance the sensitivity of temozolomide on human glioma
      cells.
AB  - Glioblastoma multiforme (GBM) continues to be associated with a dismal prognosis
      despite aggressive treatment. Significant efforts are being made to develop new
      nanotechnology-based therapeutic and diagnostic agents. Nanoparticles can act
      directly on cancer cells or as drug carriers to enhance the cancer therapeutic
      effect. In this study, we investigated the effect of silver nanoparticles (AgNPs)
      on human glioma U251 cells and its role in the combinational use with
      Temozolomide (TMZ), an imidazotetrazine derivative of the alkylating agent
      dacarbazine, against glioma cells. AgNPs were synthesized in the sodium citrate
      system and the mean size were 26 nm in diameter. The AgNP particles showed dose
      dependent cytotoxicity on U251 cells. They also showed the ability to enhance the
      drug-sensitivity of TMZ on U251 cells. Our results revealed that AgNPs could have
      a potential application in enhancing chemotherapy for glioma.

PMID- 27893420
TI  - Prognostic value of three-dimensional echocardiographic right ventricular
      ejection fraction in patients with pulmonary arterial hypertension.
AB  - BACKGROUND: Right ventricular (RV) function is an independent predictor of
      clinical outcomes in patients with pulmonary arterial hypertension (PAH).
      However, it remains controversial which RV parameter should be measured as an
      appropriate index for the treatment of PAH. The aim of this study was to identify
      the most useful parameter that correlates with hemodynamics and predicts clinical
      outcomes in PAH. RESULTS: Most of the clinical and echocardiographic RV
      parameters were significantly correlated with pulmonary vascular resistance (PVR)
      as well as mean pulmonary arterial pressure (mPAP). Among these, three
      dimensional right ventricular ejection fraction (3DRVEF) showed the strongest
      hemodynamic correlation, followed by 6-minute walk distance. Receiver operating
      characteristic analysis of association with cardiac events including death,
      hospitalization, and intervention revealed a greater area under the curve for
      3DRVEF than for mPAP (0.78 vs. 0.74). Kaplan-Meier analysis showed that patients
      with 3DRVEF less than 38% had significantly shorter event-free survival than
      those with greater than 38% (P = 0.0007). Finally, the Cox proportional hazards
      analysis revealed that 3DRVEF, but not mPAP, was an independent predictor of
      clinical events in PAH. MATERIALS AND METHODS: Eighty-six consecutive patients
      were enrolled in this study. RV hemodynamic parameters were measured by right
      heart catheterization (RHC). RV function was assessed using two-dimensional
      speckle-tracking echocardiography and three-dimensional transthoracic
      echocardiography (3DTTE) to evaluate RV free wall global strain (RVFS) and RVEF.
      CONCLUSIONS: RVEF measured by 3DTTE could be a useful parameter for noninvasively
      assessing RV hemodynamics and predicting the clinical outcomes in PAH patients.

PMID- 27893421
TI  - PHACTR1 and SLC22A3 gene polymorphisms are associated with reduced coronary
      artery disease risk in the male Chinese Han population.
AB  - Previous studies showed that PHACTR1 and SLC22A3 are involved in coronary
      vascular development and are key determinants of cardiovascular disease risk. We
      conducted a case-control study to examine the effect of SLC22A3 and PHACTR1
      single nucleotide polymorphisms (SNPs) on CAD risk among 376 male CAD patients
      and 388 male healthy controls from China. Eleven SLC22A3 and PHACTR1 SNPs were
      selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and
      95% confidence intervals (CIs) were calculated using unconditional logistic
      regression adjusting for age. The rs9381439 minor allele "A" (OR = 0.72; 95% CI =
      0.54-0.96; p = 0.024) in an allelic model was associated with reduced CAD risk,
      as were the rs2048327 "C/C" (OR = 0.60; 95% CI: 0.37-0.97; p = 0.036) and
      rs1810126 "T/T" (OR = 0.58; 95% CI: 0.36-0.93; p = 0.024) genotypes. Likewise,
      the rs9349379 "A/G" genotype in a dominant model (p = 0.041), the rs1810126 "T/C"
      genotype in additive (p = 0.041) and recessive (p = 0.012) models, and the
      rs2048327 "C/T" genotype in a recessive model were associated with decreased CAD
      risk (p = 0.016). These results suggest several PHACTR1 and SLC22A3 polymorphisms
      are associated with decreased CAD risk in the male Chinese Han population.

PMID- 27893422
TI  - PTTG1 regulated by miR-146a-3p promotes bladder cancer migration, invasion,
      metastasis and growth.
AB  - Pituitary tumor-transforming gene 1 (PTTG1) is identified as an oncogene, and
      overexpresses in many tumors. However, the role of PTTG1 in bladder cancer (BC)
      hasn't yet been characterized well. In this study, we showed the expression of
      PTTG1 mRNA and protein were both significantly increased in BC tissues and cells.
      The PTTG1 protein levels were positive correlated with increased tumor size,
      tumor-node-metastasis (TNM) stage, lymphatic invasion and distant metastasis of
      BC. PTTG1 knockdown dramatically suppressed the migration, invasion, metastasis
      and growth, and induced senescence and cell-cycle arrest at G0/G1 phase of BC
      cells. We further identified PTTG1 was the direct target of miR-146a-3p through
      using target prediction algorithms and luciferase reporter assay. miR-146a-3p was
      low expressed and negatively correlated with PTTG1 levels in BC tissues and
      cells. miR-146a-3p overexpression inhibited migration, invasion, metastasis and
      growth, and induced senescence of BC cells. Rescue experiment suggested ectopic
      expression of miR-146a-3p and PTTG1 suppressed migration, invasion and induced
      cell cycle arrest and senescence of BC cells compared to PTTG1 overexpression,
      confirming miR-146a-3p inhibited BC progression by targeting PTTG1. In summary,
      our study found miR-146a-3p/PTTG1 axis regulated BC migration, invasion,
      metastasis and growth, and might be a targets for BC therapy.

PMID- 27893423
TI  - Efficacy and safety of icotinib in treating non-small cell lung cancer: a
      systematic evaluation and meta-analysis based on 15 studies.
AB  - Icotinib is a new epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor (TKI) that developed and used in China; this work was to evaluate its
      efficacy and safety in treating non-small cell lung cancer (NSCLC). Clinical
      studies evaluating the efficacy and safety of icotinib in treating NSCLC were
      identified from the databases of Medline, Web of Science, Embase and Cochrance
      Library. Pooled efficacy and safety of icotinib were calculated through a series
      of predefined search strategies. A total of 15 studies with 2,304 patients were
      involved in this study. The overall response rate (ORR) and disease control rate
      (DCR) of icotinib were 40.99% (95% CI: 33.77% to 48.22%) and 77.16% (95% CI:
      51.43% to 82.31%). The pooled progression-free survival (PFS) and overall
      survival (OS) were 7.34 months (95% CI: 5.60 to 9.07) and 14.98 months (95% CI:
      9.78 to 20.18). Patients with EGFR mutations exhibited better ORR (OR = 3.67, p <
      0.001), DCR (OR = 1.39, p = 0.001) and PFS (11.0 +/- 0.76 vs. 1.97 +/- 0.82
      months). Moreover, patients with rash had a higher ORR (OR = 2.14, p = 0.001)
      than those without rash. The common adverse effects (AEs) included skin rash
      (31.4%), diarrhea (14.2%), pruritus (6.7%) and hepatic toxicity (3.8%) and most
      of them were well tolerated. In conclusion, Icotinib is an effective and well
      tolerated regimen for Chinese patients with advanced NSCLC. Further randomized
      trials with large population are required to provide stronger evidence for
      icotinib in treating NSCLC.

PMID- 27893424
TI  - Accumulated promoter methylation as a potential biomarker for esophageal cancer.
AB  - We performed a two-stage molecular epidemiological study to explore DNA
      methylation profiles for potential biomarkers of esophageal squamous cell
      carcinoma (ESCC) in a Chinese population. Infinium Methylation 450K BeadChip was
      used to identify genes with differentially methylated CpG sites. Sixteen
      candidate genes were validated by sequencing 1160 CpG sites in their promoter
      regions using the Illumina MiSeq platform. When excluding sites with negative
      changes, 10 genes (BNIP3, BRCA1, CCND1, CDKN2A, HTATIP2, ITGAV, NFKB1, PIK3R1,
      PRDM16 and PTX3) showed significantly different methylation levels among cancer
      lesions, remote normal-appearing tissues, and healthy controls. PRDM16 had the
      highest diagnostic value with the AUC (95% CI) of 0.988 (0.965-1.000), followed
      by PIK3R1, with the AUC (95% CI) of 0.969 (0.928-1.000). In addition, the
      methylation status was higher in patients with advanced cancer stages. These
      results indicate that aberrant DNA methylation may be a potential biomarker for
      the diagnosis of ESCC.

PMID- 27893425
TI  - Tag SNPs of long non-coding RNA TINCR affect the genetic susceptibility to
      gastric cancer in a Chinese population.
AB  - Tissue differentiation-inducing non-protein coding RNA (TINCR) is required for
      normal epidermal differentiation. TINCR is also strongly overexpressed in human
      gastric cancer (GC) and contributes to carcinogenesis and tumor progression.
      However, the association between TINCR polymorphisms and the risk of any
      diseases, such as GC, remains unknown. In the present study, the tag single
      nucleotide polymorphisms rs8113645, rs2288947, rs8105637, and rs12610531 were
      analyzed in 602 patients with GC and 602 age- and sex-matched controls.
      Polymorphisms were genotyped using TaqMan technology. Carriers of variant
      rs8113645 and rs2288947 alleles indicated reduced risks of GC (p = 0.003 and
      0.037, respectively). A allele genotypes of rs8113645 and G allele genotypes of
      rs2288947 (rs8113645 GA and AA; rs2288947 AG and GG) were also significantly
      associated with decreased GC risk (p < 0.05). Stratification analysis displayed
      that the correlations between GC risk and variant genotypes of both rs8113645 and
      rs2288947were more evident in younger individuals, men, nonsmokers, and
      individuals from rural areas. We also demonstrated that rs8113645 GA+AA genotype
      carriers had lower TINCR mRNA expression levels compared with common genotype in
      both normal and GC tissues (p < 0.05). These results suggest that long non-coding
      RNA TINCR polymorphisms may be implicated in GC development.

PMID- 27893426
TI  - Sublethal exposure to alpha radiation (223Ra dichloride) enhances various
      carcinomas' sensitivity to lysis by antigen-specific cytotoxic T lymphocytes
      through calreticulin-mediated immunogenic modulation.
AB  - Radium-223 dichloride (Xofigo(r); 223Ra) is an alpha-emitting radiopharmaceutical
      FDA-approved for the treatment of bone metastases in patients with advanced
      castration-resistant prostate cancer. It is also being examined clinically in
      patients with breast and lung carcinoma and patients with multiple myeloma. As
      with other forms of radiation, the aim of 223Ra is to reduce tumor burden by
      directly killing tumor cells. External beam (photon) and proton radiation have
      been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T
      lymphocytes (CTLs). However, little is known about whether treatment with 223Ra
      can also induce such immunogenic modulation in tumor cells that survive
      irradiation. We examined these effects in vitro by exposing human prostate,
      breast, and lung carcinoma cells to sublethal doses of 223Ra. 223Ra significantly
      enhanced T cell-mediated lysis of each tumor type by CD8+ CTLs specific for MUC
      1, brachyury, and CEA tumor antigens. Immunofluorescence analysis revealed that
      the increase in CTL killing was accompanied by augmented protein expression of
      MHC-I and calreticulin in each tumor type, molecules that are essential for
      efficient antigen presentation. Enhanced tumor-cell lysis was facilitated by
      calreticulin surface translocation following 223Ra exposure. The phenotypic
      changes observed after treatment appear to be mediated by induction of the
      endoplasmic reticulum stress response pathway. By rendering tumor cells more
      susceptible to T cell-mediated lysis, 223Ra may potentially be effective in
      combination with various immunotherapies, particularly cancer vaccines that are
      designed to generate and expand patients' endogenous antigen-specific T-cell
      populations against specific tumor antigens.

PMID- 27893428
TI  - MicroRNA-206 is involved in the pathogenesis of ulcerative colitis via regulation
      of adenosine A3 receptor.
AB  - Increasing evidence suggests that miRNAs are widely dysregulated in ulcerative
      colitis (UC), potentially affecting UC pathogenesis, diagnosis, and therapy.
      microRNA (miR) -206 has been reported to be upregulated in UC; however, its
      function and role in UC remain unknown. Here, we elucidate the function of miR
      206 in the pathogenesis of UC. In patients with active-UC, miR-206 and adenosine
      A3 receptor (A3AR) levels were significantly upregulated and downregulated,
      respectively, and were inversely correlated. A3AR was expressed in the colon
      mucosa (particularly in colon epithelial-cell membranes). In HT-29 cells, miR-206
      downregulated A3AR mRNA/protein expression by directly targeting the A3AR 3'-UTR;
      miR-206 overexpression and knockdown respectively increased and decreased TNF
      alpha-induced nuclear NF-kappaB/p65, p-IkappaB-alpha, IKKalpha, p-IKKalpha and IL
      8/IL-1beta secretion. However, A3AR-siRNA reversed the miR-206 inhibitory effect.
      Furthermore, miR-206 increased dextran sodium sulphate-induced colitis severity
      (i.e., increased bodyweight loss, DAI score, colon shrinkage, and MPO activity),
      which was partially ameliorated by miR-206-antagomir treatment. miR-206-agomir
      treatment potently suppressed A3AR expression and increased NF-kappaB signalling
      and downstream cytokine (TNF-alpha/IL-8/IL-1beta) expression in the mouse colon,
      in contrast to miR-206-antagomir administration. Taken together, our results
      demonstrated that miR-206 has a proinflammatory role in UC by downregulating A3AR
      expression and activating NF-kappaB signalling.

PMID- 27893427
TI  - Cholesterol import and steroidogenesis are biosignatures for gastric cancer
      patient survival.
AB  - Androgens, estrogens, progesterone and related signals are reported to be
      involved in the pathology of gastric cancer. However, varied conclusions exist
      based on serum hormone levels, receptor expressions, and in vitro or in vivo
      studies. This report used a web-based gene survival analyzer to evaluate
      biochemical processes, including cholesterol importing via lipoprotein/receptors
      (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer
      patients prognosis. The sex hormone receptors (androgen receptor, progesterone
      receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density
      lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and
      steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and
      SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR,
      PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR
      B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote
      progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses
      progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm
      found that CYP19A1 is the progression confounder in surgery, HER2 positive or
      negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was
      expressed higher in the tumor compared to that in normal counterparts, and also
      promoted progression. Lastly, exemestrane (type II aromatase inhibitor)
      dramatically suppress GCa cell growth in pharmacological tolerable doses in
      vitro. This work depicts a route-specific outside-in delivery of cholesterol to
      promote disease progression, implicating a host-to-tumor macroenvironmental
      regulation. The result indicating lipoprotein-mediated cholesterol entry and
      steroidogenesis are GCa progression biosignatures. And the exemestrane clinical
      trial in GCa patients of unmet medical needs is suggested.

PMID- 27893429
TI  - MicroRNA-595 sensitizes ovarian cancer cells to cisplatin by targeting ABCB1.
AB  - Ovarian cancer is among the leading cause of cancer-related deaths in females. In
      this study, we demonstrated that miR-595 expression was downregulated in the
      ovarian cancer tissues and cell lines. miR-595 expression was lower in the lymph
      node metastases tissues than in the primary ovarian cancer tissues and normal
      tissues. Furthermore, miR-595 overexpression suppressed the ovarian cancer cell
      proliferation, colony formation and invasion and promoted the sensitivity of
      ovarian cancer cell to cisplatin. We identified ABCB1 as a direct target gene of
      miR-595 in the ovarian cancer cell. ABCB1 expression was upregulated in the
      ovarian cancer tissues and cell lines. Morevoer, the expression level of ABCB1
      was inversely correlated with miR-595 in the ovarian cancer tissues. In addition,
      overexpression of ABCB1 decreased the miR-595-overexpressing HO8910PM and SKOV-3
      cell sensitivity to cisplatin. Ectopic expression of ABCB1 promoted the miR-595
      overexpressing HO8910PM and SKOV-3 cell proliferation, colony formation and
      invasion. These data suggested that miR-595 acted a tumor suppressor role in
      ovarian cancer development and increased the sensitivity of ovarian cancer to
      cisplatin.

PMID- 27893430
TI  - KIAA0247 suppresses the proliferation, angiogenesis and promote apoptosis of
      human glioma through inactivation of the AKT and Stat3 signaling pathway.
AB  - Gliomas are the most common and aggressive type of primary adult brain tumors.
      Although KIAA0247 previously is a speculated target of the tumor suppressor gene,
      little is known about the association between KIAA0247 and glioma. In this study,
      we clearly demonstrate that KIAA0247 expression is decreased in glioma and was
      negatively correlated with the histologic grade. Overexpression of KIAA0247 in
      glioma cells inhibits proliferation, angiogenesis and promoted apoptosis of human
      glioma cells in vitro. In contrast, knockdown of KIAA0247 increases the
      proliferation, angiogenesis and decreases apoptosis of these cells. In a tumor
      xenograft model, overexpression of KIAA0247 suppresses tumor growth of glioma
      cells in vivo, while KIAA0247 knockdown promotes the tumor growth.
      Mechanistically, overexpression of KIAA0247 is able to inhibit phosphorylation of
      AKT and Stat3 in glioma cells, resulting in inactivation of the AKT and Stat3
      signaling pathways, this ultimately decreases the expression of PCNA, CyclinD1,
      Bcl2 and VEGF. Collectively, these data indicate that KIAA0247 may work as a
      tumor suppressor gene in glioma and a promising therapeutic target for gliomas.

PMID- 27893431
TI  - Dysregulated human Tyrosyl-DNA phosphodiesterase I acts as cellular toxin.
AB  - Tyrosyl-DNA phosphodiesterase I (TDP1) hydrolyzes the drug-stabilized 3'phospho
      tyrosyl bond formed between DNA topoisomerase I (TOPO1) and DNA. TDP1-mediated
      hydrolysis uses a nucleophilic histidine (Hisnuc) and a general acid/base
      histidine (Hisgab). A Tdp1Hisgab to Arg mutant identified in patients with the
      autosomal recessive neurodegenerative disease SCAN1 causes stabilization of the
      TDP1-DNA intermediate. Based on our previously reported Hisgab-substitutions
      inducing yeast toxicity (Gajewski et al. J. Mol. Biol. 415, 741-758, 2012), we
      propose that converting TDP1 into a cellular poison by stabilizing the covalent
      enzyme-DNA intermediate is a novel therapeutic strategy for cancer treatment.
      Here, we analyzed the toxic effects of two TDP1 catalytic mutants in HEK293
      cells. Expression of human Tdp1HisnucAla and Tdp1HisgabAsn mutants results in
      stabilization of the covalent TDP1-DNA intermediate and induces cytotoxicity.
      Moreover, these mutants display reduced in vitro catalytic activity compared to
      wild type. Co-treatment of Tdp1mutant with topotecan shows more than additive
      cytotoxicity. Overall, these results support the hypothesis that stabilization of
      the TDP1-DNA covalent intermediate is a potential anti-cancer therapeutic
      strategy.

PMID- 27893432
TI  - MicroRNA-34a expression levels in serum and intratumoral tissue can predict bone
      metastasis in patients with hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) patients with bone metastasis (BM) suffer from
      pain and other symptoms that significantly reduce their quality of life. We
      screened a microRNA (miRNA) microarray to identify potential serum biomarkers for
      BM in HCC patients. A miRNA microarray was used to screen for BM-related miRNAs
      in paired serum samples from HCC patients with BM and from HCC patients without
      BM. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to
      quantify candidate miRNAs in serum samples from 106 independent HCC patients.
      Levels of candidate miRNAs in tissue samples from an independent cohort of 296
      HCC patients were evaluated by in situ hybridization and intratumoral tissue
      microarray. The migration and invasion capabilities of HCCLM3 and SMMC-7721 cells
      were evaluated following treatment with a mimic and an inhibitor of miR-34a.
      Ninety miRNAs were differentially expressed in sera from HCC patients with BM
      when compared with sera from non-BM HCC patients (P < 0.05). Only miR-34a and miR
      498 had false discovery rates (FDRs) < 0.05. In cohorts of 106 and 296 HCC
      patients, we found that reduced serum and intratumoral miR-34a expression levels
      were independent risk factors for developing BM. Migration and invasion
      experiments indicated that a reverse correlation existed between miR-34a and HCC
      tumor migration and invasion. This study demonstrates the potential for the use
      of miR-34a as a serum and intratumoral tissue biomarker for predicting the risk
      of BM in HCC patients.

PMID- 27893435
TI  - Non-targeted effects and radiation-induced cancer.

PMID- 27893433
TI  - Regulation of brachyury by fibroblast growth factor receptor 1 in lung cancer.
AB  - Recent evidence suggests that T-box transcription factor brachyury plays an
      important role in lung cancer development and progression. However, the
      mechanisms underlying brachyury-driven cellular processes remain unclear. Here we
      found that fibroblast growth factor receptor 1/mitogen-activated protein kinase
      (FGFR1/MAPK) signaling regulated brachyury in lung cancer. Analysis of FGFR1-4
      and brachyury expression in human lung tumor tissue and cell lines found that
      only expression of FGFR1 was positively correlated with brachyury expression.
      Specific knockdown of FGFR1 by siRNA suppressed brachyury expression and
      epithelial-mesenchymal transition (EMT) (upregulation of E-cadherin and beta
      catenin and downregulation of Snail and fibronectin), whereas forced
      overexpression of FGFR1 induced brachyury expression and promoted EMT in lung
      cancer cells. Activation of fibroblast growth factor (FGF)/FGFR1 signaling
      promoted phosphorylated MAPK extracellular signal-regulated kinase (ERK) 1/2
      translocation from cytoplasm to nucleus, upregulated brachyury expression, and
      increased cell growth and invasion. In addition, human lung cancer cells with
      higher brachyury expression were more sensitive to inhibitors targeting
      FGFR1/MAPK pathway. These findings suggest that FGFR1/MAPK may be important for
      brachyury activation in lung cancer, and this pathway may be an appealing
      therapeutic target for a subset of brachyury-driven lung cancer.

PMID- 27893436
TI  - Carbon nanotubes as carriers of Panax ginseng metabolites and enhancers of
      ginsenosides Rb1 and Rg1 anti-cancer activity.
AB  - A major benefit to nanomaterial based-medicine is the ability to provide
      nanosized vehicles for sporadic metabolites. Here, we describe how the
      conjugation of valuable ginseng secondary metabolites (ginsenoside Rb1 or Rg1)
      with carbon nanotubes (CNT) can enhance their anti-proliferative and anti-cancer
      effects. Ginsenoside-CNT conjugate (Rb-CNT or Rg-CNT) permitted the ginsenosides
      to be used at a low dose, yet achieve a higher incidence of cancer killing. We
      were able to demonstrate that the ginsenoside-CNT conjugate can decrease cell
      viability up to 62% in breast cancer cells (MCF-7) and enhance antiproliferation
      of drug-resistant pancreatic cancer cells (PANC-1) by 61%. The interaction of the
      ginsenoside-CNT conjugate with breast cancer cells was studied using Raman
      Spectroscopy mapping. Total transcriptome profiling (Affymetrix platform) of MCF
      7 cells treated with the ginsenoside-CNT conjugate shows that a number of
      cellular, apoptotic and response to stimulus processes were affected. Therefore,
      our data confirmed the potential use of CNT as a drug delivery system.

PMID- 27893437
TI  - Silicon nanowire heterostructures for advanced energy and environmental
      applications: a review.
AB  - Semiconductor nanowires (NWs), in particular Si NWs, have attracted much
      attention in the last decade for their unique electronic properties and potential
      applications in several emerging areas. With the introduction of heterostructures
      (HSs) on NWs, new functionalities are obtained and the device performance is
      improved significantly in many cases. Due to the easy fabrication techniques,
      excellent optoelectronic properties and compatibility of forming HSs with
      different inorganic/organic materials, Si NW HSs have been utilized in various
      configurations and device architectures. Herein, we review the recent
      developments in Si NW HS-based devices including the fabrication techniques,
      properties (e.g., light emitting, antireflective, photocatalytic, electrical,
      photovoltaic, sensing etc) and related emerging applications in energy
      generation, conversion, storage, and environmental cleaning and monitoring. In
      particular, recent advances in Si NW HS-based solar photovoltaics, light-emitting
      devices, thermoelectrics, Li-ion batteries, supercapacitors, hydrogen generation,
      artificial photosynthesis, photocatalytic degradation of organic dyes in water
      treatment, chemical and gas sensors, biomolecular sensors for microbial
      monitoring etc have been addressed in detail. The problems and challenges in
      utilizing Si NW HSs in device applications and the key parameters to improve the
      device performance are pointed out. The recent trends in the commercial
      applications of Si NW HS-based devices and future outlook of the field are
      presented at the end.

PMID- 27893438
TI  - Communicating the significance of different levels of dose.

PMID- 27893439
TI  - One step spray-coated TiO2 electron-transport layers for decent perovskite solar
      cells on large and flexible substrates.
AB  - Spray-coating as a facile and quantitative method was introduced to prepare thin
      and continuous TiO2 compact layers on different substrates for perovskite solar
      cells. The as-prepared film is highly transparent and smooth, which is of
      significance in perovskite solar cells to decrease incident light loss and
      facilitate the film cast and electric contact. The compact TiO2 layer shows
      excellent performance when coated with perovskite and assembled into a device.
      Since it provides unlimited substrate size, patterning function and the TiO2 used
      for spray-coating is well crystallized, this method has huge potential for mass
      production and great adaptability for a variety of applications.

PMID- 27893434
TI  - Neuroinflammatory and cognitive consequences of combined radiation and
      immunotherapy in a novel preclinical model.
AB  - BACKGROUND: Cancer patients often report behavioral and cognitive changes
      following cancer treatment. These effects can be seen in patients who have not
      yet received treatment or have received only peripheral (non-brain) irradiation.
      Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate
      remarkable efficacy with respect to tumor outcomes by enhancing the
      proinflammatory environment in the tumor. However, a proinflammatory environment
      in the brain mediates cognitive impairments in other neurological disorders and
      may affect brain function in cancer patients receiving these novel treatments.
      Currently, gaps exist as to whether these treatments impact the brain in
      individuals with or without tumors and with regard to the underlying mechanisms.
      RESULTS: Combined treatment with precision RT and checkpoint inhibitor IT
      achieved control of tumor growth. However, BALB/c mice receiving combined
      treatment demonstrated changes in measures of anxiety levels, regardless of tumor
      status. C57BL/6J mice with tumors demonstrated increased anxiety, except
      following combined treatment. Object recognition memory was impaired in C57BL/6J
      mice without tumors following combined treatment. All mice with tumors showed
      impaired object recognition, except those treated with RT alone. Mice with tumors
      demonstrated impaired amygdala-dependent cued fear memory, while maintaining
      hippocampus-dependent context fear memory. These behavioral alterations and
      cognitive impairments were accompanied by increased microglial activation in mice
      receiving immunotherapy alone or combined with RT. Finally, based on tumor
      status, there were significant changes in proinflammatory cytokines (IFN-gamma,
      IL-6, IL-5, IL-2, IL-10) and a growth factor (FGF-basic). MATERIALS AND METHODS:
      Here we test the hypothesis that IT combined with peripheral RT have detrimental
      behavioral and cognitive effects as a result of an enhanced proinflammatory
      environment in the brain. BALB/c mice with or without injected hind flank CT26
      colorectal carcinoma or C57BL/6J mice with or without Lewis Lung carcinoma were
      used for all experiments. Checkpoint inhibitor IT, using an anti-CTLA-4 antibody,
      and precision CT-guided peripheral RT alone and combined were used to closely
      model clinical treatment. We assessed behavioral and cognitive performance and
      investigated the immune environment using immunohistochemistry and multiplex
      assays to analyze proinflammatory mediators. CONCLUSIONS: Although combined
      treatment achieved tumor growth control, it affected the brain and induced
      changes in measures of anxiety, cognitive impairments, and neuroinflammation.

PMID- 27893440
TI  - A 3D reconstruction algorithm for magneto-acoustic tomography with magnetic
      induction based on ultrasound transducer characteristics.
AB  - In this study we present a three-dimensional (3D) reconstruction algorithm for
      magneto-acoustic tomography with magnetic induction (MAT-MI) based on the
      characteristics of the ultrasound transducer. The algorithm is investigated to
      solve the blur problem of the MAT-MI acoustic source image, which is caused by
      the ultrasound transducer and the scanning geometry. First, we established a
      transducer model matrix using measured data from the real transducer. With
      reference to the S-L model used in the computed tomography algorithm, a 3D
      phantom model of electrical conductivity is set up. Both sphere scanning and
      cylinder scanning geometries are adopted in the computer simulation. Then, using
      finite element analysis, the distribution of the eddy current and the acoustic
      source as well as the acoustic pressure can be obtained with the transducer model
      matrix. Next, using singular value decomposition, the inverse transducer model
      matrix together with the reconstruction algorithm are worked out. The acoustic
      source and the conductivity images are reconstructed using the proposed
      algorithm. Comparisons between an ideal point transducer and the realistic
      transducer are made to evaluate the algorithms. Finally, an experiment is
      performed using a graphite phantom. We found that images of the acoustic source
      reconstructed using the proposed algorithm are a better match than those using
      the previous one, the correlation coefficient of sphere scanning geometry is
      98.49% and that of cylinder scanning geometry is 94.96%. Comparison between the
      ideal point transducer and the realistic transducer shows that the correlation
      coefficients are 90.2% in sphere scanning geometry and 86.35% in cylinder
      scanning geometry. The reconstruction of the graphite phantom experiment also
      shows a higher resolution using the proposed algorithm. We conclude that the
      proposed reconstruction algorithm, which considers the characteristics of the
      transducer, can obviously improve the resolution of the reconstructed image. This
      study can be applied to analyse the effect of the position of the transducer and
      the scanning geometry on imaging. It may provide a more precise method to
      reconstruct the conductivity distribution in MAT-MI.

PMID- 27893441
TI  - Engineering tumor cell targeting in nanoscale amyloidal materials.
AB  - Bacterial inclusion bodies are non-toxic, mechanically stable and functional
      protein amyloids within the nanoscale size range that are able to naturally
      penetrate into mammalian cells, where they deliver the embedded protein in a
      functional form. The potential use of inclusion bodies in protein delivery or
      protein replacement therapies is strongly impaired by the absence of specificity
      in cell binding and penetration, thus preventing targeting. To address this
      issue, we have here explored whether the genetic fusion of two tumor-homing
      peptides, the CXCR4 ligands R9 and T22, to an inclusion body-forming green
      fluorescent protein (GFP), would keep the interaction potential and the
      functionality of the fused peptides and then confer CXCR4 specificity in cell
      binding and further uptake of the materials. The fusion proteins have been well
      produced in Escherichia coli in their full-length form, keeping the potential for
      fluorescence emission of the partner GFP. By using specific inhibitors of CXCR4
      binding, we have demonstrated that the engineered protein particles are able to
      penetrate CXCR4+ cells, in a receptor-mediated way, without toxicity or visible
      cytopathic effects, proving the availability of the peptide ligands on the
      surface of inclusion bodies. Since no further modification is required upon their
      purification, the biological production of genetically targeted inclusion bodies
      opens a plethora of cost-effective possibilities in the tissue-specific
      intracellular transfer of functional proteins through the use of structurally and
      functionally tailored soft materials.

PMID- 27893442
TI  - Inconsistency of a recently proposed method for assessing magnetic field exposure
      for protection against peripheral nerve stimulation in occupational situations.
AB  - A non-binding guide to practical implementation of European Directive 2013/35/EU
      concerning the limitation of occupational exposure against electromagnetic fields
      has been published recently. With regard to exposure assessment this guide
      proposes practically applicable assessment methods for non-uniform and non
      sinusoidal environmental electric and magnetic fields, respectively. For non
      sinusoidal magnetic fields in the low frequency range this guide proposes a time
      domain assessment (TDA) method, claimed to reduce the overestimation of exposure
      inherent to other assessment methods while being based on fundamental
      physiological principles regarding nerve stimulation. In the present paper we
      demonstrate that the proposed TDA method is not consistent with the obvious
      underlying principles of directive 2013/35/EU. Based on practically relevant
      waveforms and general considerations it can be shown that external magnetic
      fields may be deemed compliant by the TDA method although the underlying exposure
      limit values defined in 2013/35/EU may be exceeded. We therefore strongly
      recommend that the TDA method is removed from the guide for implementing
      2013/35/EU as soon as possible.

PMID- 27893444
TI  - Response to criticism of the paper titled 'Non-targeted effects and radiation
      induced carcinogenesis: a review'.

PMID- 27893443
TI  - Health effects of the Windscale Pile fire.

PMID- 27893445
TI  - A method for high-energy, low-dose mammography using edge illumination x-ray
      phase-contrast imaging.
AB  - Since the breast is one of the most radiosensitive organs, mammography is
      arguably the area where lowering radiation dose is of the uttermost importance.
      Phase-based x-ray imaging methods can provide opportunities in this sense, since
      they do not require x-rays to be stopped in tissue for image contrast to be
      generated. Therefore, x-ray energy can be considerably increased compared to
      those usually exploited by conventional mammography. In this article we show how
      a novel, optimized approach can lead to considerable dose reductions. This was
      achieved by matching the edge-illumination phase method, which reaches very high
      angular sensitivity also at high x-ray energies, to an appropriate image
      processing algorithm and to a virtually noise-free detection technology capable
      of reaching almost 100% efficiency at the same energies. Importantly, while proof
      of-concept was obtained at a synchrotron, the method has potential for a
      translation to conventional sources.

PMID- 27893446
TI  - Stability of radiomic features in CT perfusion maps.
AB  - This study aimed to identify a set of stable radiomic parameters in CT perfusion
      (CTP) maps with respect to CTP calculation factors and image discretization, as
      an input for future prognostic models for local tumor response to chemo
      radiotherapy. Pre-treatment CTP images of eleven patients with oropharyngeal
      carcinoma and eleven patients with non-small cell lung cancer (NSCLC) were
      analyzed. 315 radiomic parameters were studied per perfusion map (blood volume,
      blood flow and mean transit time). Radiomics robustness was investigated
      regarding the potentially standardizable (image discretization method, Hounsfield
      unit (HU) threshold, voxel size and temporal resolution) and non-standardizable
      (artery contouring and noise threshold) perfusion calculation factors using the
      intraclass correlation (ICC). To gain added value for our model radiomic
      parameters correlated with tumor volume, a well-known predictive factor for local
      tumor response to chemo-radiotherapy, were excluded from the analysis. The
      remaining stable radiomic parameters were grouped according to inter-parameter
      Spearman correlations and for each group the parameter with the highest ICC was
      included in the final set. The acceptance level was 0.9 and 0.7 for the ICC and
      correlation, respectively. The image discretization method using fixed number of
      bins or fixed intervals gave a similar number of stable radiomic parameters
      (around 40%). The potentially standardizable factors introduced more variability
      into radiomic parameters than the non-standardizable ones with 56-98% and 43-58%
      instability rates, respectively. The highest variability was observed for voxel
      size (instability rate  >97% for both patient cohorts). Without standardization
      of CTP calculation factors none of the studied radiomic parameters were stable.
      After standardization with respect to non-standardizable factors ten radiomic
      parameters were stable for both patient cohorts after correction for inter
      parameter correlations. Voxel size, image discretization, HU threshold and
      temporal resolution have to be standardized to build a reliable predictive model
      based on CTP radiomics analysis.

PMID- 27893447
TI  - Room temperature nanostructured graphene transistor with high on/off ratio.
AB  - We report the batch fabrication of graphene field-effect-transistors (GFETs) with
      nanoperforated graphene as channel. The transistors were cut and encapsulated.
      The encapsulated GFETs display saturation regions that can be tuned by modifying
      the top gate voltage, and have on/off ratios of at least 2 * 103 at room
      temperature and at small drain and gate voltages. In addition, the nanoperforated
      GFETs display orders of magnitude higher photoresponses than any room-temperature
      graphene detector configurations that do not involve heterostructures with
      bandgap materials.

PMID- 27893448
TI  - In-field evaluation of the impact of ageing and fading effects on annual radon
      concentration measurements for two different techniques.
AB  - Measurements covering a 1 year period are often used and required by legislation
      to assess the average radon concentration within a house or a workplace. This
      kind of long-term measurement-generally carried out with techniques based on
      nuclear track detectors-can be affected by a reduction in sensitivity due to
      ageing and fading of latent tracks during the exposure period, thus resulting in
      an underestimation of the actual average concentration. In order to evaluate in
      field conditions the ageing and fading effects on annual radon concentration
      measurements, two different studies in a large sample of rooms in dwellings (162)
      and in workplaces (432) were conducted using two different techniques (detector
      and track read-out system): (i) CR-39 plastics readout with a fully automated
      image analysis system, and (ii) LR 115 films with a spark-counter for track
      counting. Study design and data analysis aimed to evaluate both the average and
      the variability of ageing and fading effects in real conditions, and to reduce
      and separate the contribution of measurement uncertainty to the observed
      variability. For the CR-39 based technique, the results show that radon
      concentration measurements over a 12month period are on average about 16% lower
      than those evaluated with measurements of two consecutive 6 month periods,
      implying the need for a correction factor to avoid measurement bias (i.e.
      underestimation) due to ageing and fading effects. The observed variability of
      ageing and fading effects among the sampled rooms is not negligible (coefficient
      of variation about 18%), although a considerable fraction is attributable to
      measurement uncertainty, which is presumably not related to ageing and fading.
      For the technique based on LR 115 spark counting, ageing and fading do not
      significantly affect the results of radon concentration measurement.

PMID- 27893449
TI  - Biaxially stretchable silver nanowire conductive film embedded in a taro leaf
      templated PDMS surface.
AB  - A biaxially wave-shaped polydimethylsiloxane (PDMS) surface was developed simply
      by using a taro leaf as the template. The resulting leaf-templated PDMS (L-PDMS)
      possesses a micro-sized curved interface structure, which is greatly beneficial
      for the exact embedding of a silver nanowire (AgNW) network conductive film
      covering the L-PDMS surface. The intrinsically curved AgNW/L-PDMS film surface,
      without any dangling nanowire, could prevent the fracture of AgNWs due to
      stretching stress even after cyclic stretching. More importantly, it also
      exhibited a biaxial stretchability, which showed ultra-stable resistance after
      continuous stretching for 100 cycles each in X- and Y-directions. This biaxially
      stretchable AgNW/L-PDMS film could extend the application fields in stretchable
      electronics.

PMID- 27893450
TI  - Parental wishes for continued internal radiation contamination screenings in
      Fukushima schoolchildren.

PMID- 27893451
TI  - Rotating and translating anthropomorphic head voxel models to establish an
      horizontal Frankfort plane for dental CBCT Monte Carlo simulations: a dose
      comparison study.
AB  - In order to carry out Monte Carlo (MC) dosimetry studies, voxel phantoms,
      modeling human anatomy, and organ-based segmentation of CT image data sets are
      applied to simulation frameworks. The resulting voxel phantoms preserve patient
      CT acquisition geometry; in the case of head voxel models built upon head CT
      images, the head support with which CT scanners are equipped introduces an
      inclination to the head, and hence to the head voxel model. In dental cone beam
      CT (CBCT) imaging, patients are always positioned in such a way that the
      Frankfort line is horizontal, implying that there is no head inclination. The
      orientation of the head is important, as it influences the distance of critical
      radiosensitive organs like the thyroid and the esophagus from the x-ray tube.
      This work aims to propose a procedure to adjust head voxel phantom orientation,
      and to investigate the impact of head inclination on organ doses in dental CBCT
      MC dosimetry studies. The female adult ICRP, and three in-house-built paediatric
      voxel phantoms were in this study. An EGSnrc MC framework was employed to
      simulate two commonly used protocols; a Morita Accuitomo 170 dental CBCT scanner
      (FOVs: 60  *  60 mm2 and 80  *  80 mm2, standard resolution), and a 3D Teeth
      protocol (FOV: 100  *  90 mm2) in a Planmeca Promax 3D MAX scanner. Result
      analysis revealed large absorbed organ dose differences in radiosensitive organs
      between the original and the geometrically corrected voxel models of this study,
      ranging from  -45.6% to 39.3%. Therefore, accurate dental CBCT MC dose
      calculations require geometrical adjustments to be applied to head voxel models.

PMID- 27893452
TI  - Confounding of the association between radiation exposure from CT scans and risk
      of leukemia and brain tumors by cancer susceptibility syndromes.
AB  - Recent studies linking radiation exposure from pediatric computed tomography (CT)
      to increased risks of leukemia and brain tumors lacked data to control for cancer
      susceptibility syndromes (CSS). These syndromes might be confounders because they
      are associated with an increased cancer risk and may increase the likelihood of
      pediatric CT scans. We identify CSS predisposing to leukemia and brain tumors
      through a systematic literature search and summarize prevalence and risk. Since
      empirical evidence is lacking in published literature on patterns of CT use for
      most types of CSS, we estimate confounding bias of relative risks (RR) for
      categories of radiation exposure based on expert opinion about patterns of CT
      scans among CSS patients. We estimate that radiation-related RRs for leukemia are
      not meaningfully confounded by Down syndrome, Noonan syndrome and other CSS.
      Moreover, tuberous sclerosis complex, von Hippel-Lindau disease,
      neurofibromatosis type 1 and other CSS do not meaningfully confound RRs for brain
      tumors. Empirical data on the use of CT scans among CSS patients is urgently
      needed. Our assessment indicates that associations with radiation exposure from
      pediatric CT scans and leukemia or brain tumors reported in previous studies are
      unlikely to be substantially confounded by unmeasured CSS.

PMID- 27893453
TI  - A geographical study of thyroid cancer incidence in north-west England following
      the Windscale nuclear reactor fire of 1957.
AB  - The Windscale nuclear reactor fire at Sellafield, United Kingdom, in October 1957
      led to an uncontrolled release of iodine-131 (radioactive half-life, 8 d) into
      the atmosphere. Contamination from the accident was most pronounced in the
      counties of Cumbria and Lancashire, north-west England. Radioiodine concentrates
      in the thyroid gland producing an excess risk of thyroid cancer, notably among
      those exposed as children, which persists into later life. For an initial
      investigation of thyroid cancer incidence in north-west England, data were
      obtained on cases of thyroid cancer among people born during 1929-1973 and
      diagnosed during 1974-2012 while resident in England, together with corresponding
      populations. Incidence rate ratios (IRRs), with Poisson 95% confidence intervals
      (CIs), compared thyroid cancer incidence rates in Cumbria and in Lancashire with
      those in the rest of England. For those aged  <20 years in 1958, a statistically
      significantly increased IRR was found for those diagnosed during 1974-2012 while
      living in Cumbria (IRR  =  1.29; 95% CI 1.09-1.52), but the equivalent IRR for
      Lancashire was marginally non-significantly decreased (IRR  =  0.91; 95% CI 0.80
      1.04). This pattern of IRRs was also apparent for earlier births, and the
      significantly increased IRR in Cumbria extended to individuals born in 1959-1963,
      who would not have been exposed to iodine-131 from the Windscale accident.
      Moreover, significant overdispersion was present in the temporal distributions of
      the IRRs, so that Poisson CIs substantially underestimate statistical
      uncertainties. Consequently, although further investigations are required to
      properly understand the unusual patterns of thyroid cancer IRRs in Cumbria and
      Lancashire, the results of this preliminary study are not consistent with an
      effect of exposure to iodine-131 from the Windscale accident.

PMID- 27893454
TI  - Incoherent magnetization dynamics in strain mediated switching of
      magnetostrictive nanomagnets.
AB  - Micromagnetic studies of the magnetization change in magnetostrictive nanomagnets
      subjected to stress are performed for nanomagnets of different sizes. The
      interplay between demagnetization, exchange and stress anisotropy energies is
      used to explain the rich physics of size-dependent magnetization dynamics induced
      by modulating stress anisotropy in planar nanomagnets. These studies have
      important implications for strain mediated ultralow energy magnetization control
      in nanomagnets and its application in energy-efficient nanomagnetic computing
      devices.

PMID- 27893455
TI  - Patient radiation doses in paediatric interventional cardiology procedures: a
      review.
AB  - A large number of investigations into the radiation doses from x-ray guided
      interventional cardiology procedures in children have been carried out in recent
      years. A review was conducted of these studies, gathering data on kerma area
      product (P KA), fluoroscopic screening time (FT), air kerma, and estimates of
      effective dose and organ doses. The majority of studies focus on P KA and FT with
      no estimation of dose to the patient. A greater than ten-fold variation in
      average P KA was found between different studies, even where data were stratified
      by patient age or weight. Typical values of P KA were 0.6-10 Gy . cm2 (<1 year/10
      kg), 1.5-30 Gy . cm2 (1-5 years), 2-40 Gy . cm2 (5-10 years), 5-100 Gy . cm2 (10
      16 years) and 10-200 Gy . cm2 (>16 years). P KA was lowest for heart biopsy (0.3
      10 Gy . cm2 for all ages combined) and atrial septostomy (0.4-4.0 Gy . cm2), and
      highest for pulmonary artery angioplasty (1.5-35 Gy . cm2) and right ventricular
      outflow tract dilatation (139 Gy . cm2). Most estimates of patient dose were in
      the form of effective dose (typically 3-15 mSv) which is of limited usefulness in
      individualised risk assessment. Few studies estimated organ doses. Despite
      advances in radiation protection, recent publications have reported surprisingly
      large doses, as represented by P KA and air kerma. There is little indication of
      a fall in these dose indicators over the last 15 years. Nor is there much
      suggestion of a fall in doses associated with the use of flat panel detectors, as
      opposed to image intensifiers. An assessment of the impact of radiation dose in
      the context of overall patient outcome is required.

PMID- 27893456
TI  - Updated effective doses in radiology.
AB  - The aim of this study was to review recent literature in order to provide updated
      values of the typical effective doses associated with the top 20 imaging tests
      for adults and children and for the most widely used set of weights (ICRP60) as
      well as for the most recent one (ICRP103). We performed a systematic research on
      radiation dosimetry in radiology published from 2007 onwards through the Medline,
      Embase and Cochrane Library Plus databases. We also included studies backed by
      scientific or governmental organizations. Other variables included: year and type
      of study (survey or descriptive), country, method and sample used for the
      measurement. Mean effective dose, minimum, maximum and standard deviation were
      calculated. We compared our results with previous evidence and with data from
      DDM2. We included 27 articles and 5 web references in the study. A total of 378
      values from the 20 procedures included were obtained, 280 (74%) using ICRP60 and
      98 (26%) using ICRP103. Effective doses for CT procedures in children were very
      similar to those for adults, with the exception of CT Trunk, but fluoroscopy
      procedures had consistently lower dose. There were differences between the
      current data with either ICRP60 or ICRP103, and the previous published data. In
      conclusion, we provided the best available evidence from literature to evaluate
      the effective dose received by each patient for the most typical examinations.
      According to the recommendations from the Report 154 and from the European
      Council Directive, these results could also be useful to estimate the range of
      average exposures to the population.

PMID- 27893457
TI  - Core ethical values of radiological protection applied to Fukushima case:
      reflecting common morality and cultural diversities.
AB  - The International Commission on Radiological Protection (ICRP) has established
      Task Group 94 (TG94) to develop a publication to clarify the ethical foundations
      of the radiological protection system it recommends. This TG identified four core
      ethical values which structure the system: beneficence and non-maleficence,
      prudence, justice, and dignity. Since the ICRP is an international organization,
      its recommendations and guidance should be globally applicable and acceptable.
      Therefore, first this paper presents the basic principles of the ICRP
      radiological protection system and its core ethical values, along with a
      reflection on the variation of these values in Western and Eastern cultural
      traditions. Secondly, this paper reflects upon how these values can be applied in
      difficult ethical dilemmas as in the case of the emergency and post-accident
      phases of a nuclear power plant accident, using the Fukushima case to illustrate
      the challenges at stake. We found that the core ethical values underlying the
      ICRP system of radiological protection seem to be quite common throughout the
      world, although there are some variations among various cultural contexts.
      Especially we found that 'prudence' would call for somewhat different
      implementation in each cultural context, balancing and integrating sometime
      conflicting values, but always with objectives to achieve the well-being of
      people, which is itself the ultimate aim of the radiological protection system.

PMID- 27893458
TI  - Requirements for dynamical differential phase contrast x-ray imaging with a
      laboratory source.
AB  - X-ray phase contrast enables weakly-attenuating structures to be imaged, with
      bright synchrotron sources adding the ability to capture time sequences and
      analyse sample dynamics. Here, we describe the translation of dynamical
      differential phase contrast imaging from the synchrotron to a compact x-ray
      source, in order to achieve this kind of time sequence imaging in the laboratory.
      We formulate broadly-applicable set-up guidelines for the single-grid, single
      exposure imaging technique using a divergent source, exploring the experimental
      factors that restrict set-up size, imaging sensitivity and sample size.
      Experimental images are presented using the single-grid phase contrast technique
      with a steel attenuation grid and a liquid-metal-jet x-ray source, enabling
      exposure times as short as 0.5 s for dynamic imaging. Differential phase contrast
      images were retrieved from phantoms, incorporating noise filtering to improve the
      low-count images encountered when imaging dynamics using short exposures.

PMID- 27893459
TI  - Extended T2-IVIM model for correction of TE dependence of pseudo-diffusion volume
      fraction in clinical diffusion-weighted magnetic resonance imaging.
AB  - The bi-exponential intravoxel-incoherent-motion (IVIM) model for diffusion
      weighted MRI (DWI) fails to account for differential T 2 s in the model
      compartments, resulting in overestimation of pseudodiffusion fraction f. An
      extended model, T2-IVIM, allows removal of the confounding echo-time (TE)
      dependence of f, and provides direct compartment T 2 estimates. Two consented
      healthy volunteer cohorts (n  =  5, 6) underwent DWI comprising multiple TE/b
      value combinations (Protocol 1: TE  =  62-102 ms, b  =  0-250 mm-2s, 30
      combinations. Protocol 2: 8 b-values 0-800 mm-2s at TE  =  62 ms, with 3
      additional b-values 0-50 mm-2s at TE  =  80, 100 ms; scanned twice). Data from
      liver ROIs were fitted with IVIM at individual TEs, and with the T2-IVIM model
      using all data. Repeat-measures coefficients of variation were assessed for
      Protocol 2. Conventional IVIM modelling at individual TEs (Protocol 1)
      demonstrated apparent f increasing with longer TE: 22.4  +/-  7% (TE  =  62 ms)
      to 30.7  +/-  11% (TE  =  102 ms); T2-IVIM model fitting accounted for all data
      variation. Fitting of Protocol 2 data using T2-IVIM yielded reduced f estimates
      (IVIM: 27.9  +/-  6%, T2-IVIM: 18.3  +/-  7%), as well as T 2  =  42.1  +/-  7
      ms, 77.6  +/-  30 ms for true and pseudodiffusion compartments, respectively. A
      reduced Protocol 2 dataset yielded comparable results in a clinical time frame
      (11 min). The confounding dependence of IVIM f on TE can be accounted for using
      additional b/TE images and the extended T2-IVIM model.

PMID- 27893461
TI  - Dual modulation of MCL-1 and mTOR determines the response to sunitinib.
AB  - Most patients who initially respond to treatment with the multi-tyrosine kinase
      inhibitor sunitinib eventually relapse. Therefore, developing a deeper
      understanding of the contribution of sunitinib's numerous targets to the clinical
      response or to resistance is crucial. Here, we have shown that cancer cells
      respond to clinically relevant doses of sunitinib by enhancing the stability of
      the antiapoptotic protein MCL-1 and inducing mTORC1 signaling, thus evoking
      little cytotoxicity. Inhibition of MCL-1 or mTORC1 signaling sensitized cells to
      clinically relevant doses of sunitinib in vitro and was synergistic with
      sunitinib in impairing tumor growth in vivo, indicating that these responses are
      triggered as prosurvival mechanisms that enable cells to tolerate the cytotoxic
      effects of sunitinib. Furthermore, higher doses of sunitinib were cytotoxic,
      triggered a decline in MCL-1 levels, and inhibited mTORC1 signaling.
      Mechanistically, we determined that sunitinib modulates MCL-1 stability by
      affecting its proteasomal degradation. Dual modulation of MCL-1 stability at
      different dose ranges of sunitinib was due to differential effects on ERK and
      GSK3beta activity, and the latter also accounted for dual modulation of mTORC1
      activity. Finally, comparison of patient samples prior to and following sunitinib
      treatment suggested that increases in MCL-1 levels and mTORC1 activity correlate
      with resistance to sunitinib in patients.

PMID- 27893462
TI  - Biallelic mutations in IRF8 impair human NK cell maturation and function.
AB  - Human NK cell deficiencies are rare yet result in severe and often fatal disease,
      particularly as a result of viral susceptibility. NK cells develop from
      hematopoietic stem cells, and few monogenic errors that specifically interrupt NK
      cell development have been reported. Here we have described biallelic mutations
      in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK
      cell deficiency that results in fatal and severe viral disease. Compound
      heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in
      a paucity of mature CD56dim NK cells and an increase in the frequency of the
      immature CD56bright NK cells, and this impairment in terminal maturation was also
      observed in Irf8-/-, but not Irf8+/-, mice. We then determined that impaired
      maturation was NK cell intrinsic, and gene expression analysis of human NK cell
      developmental subsets showed that multiple genes were dysregulated by IRF8
      mutation. The phenotype was accompanied by deficient NK cell function and was
      stable over time. Together, these data indicate that human NK cells require IRF8
      for development and functional maturation and that dysregulation of this function
      results in severe human disease, thereby emphasizing a critical role for NK cells
      in human antiviral defense.

PMID- 27893460
TI  - TGF-beta1 modulates microglial phenotype and promotes recovery after
      intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH) is a devastating form of stroke that results from
      the rupture of a blood vessel in the brain, leading to a mass of blood within the
      brain parenchyma. The injury causes a rapid inflammatory reaction that includes
      activation of the tissue-resident microglia and recruitment of blood-derived
      macrophages and other leukocytes. In this work, we investigated the specific
      responses of microglia following ICH with the aim of identifying pathways that
      may aid in recovery after brain injury. We used longitudinal transcriptional
      profiling of microglia in a murine model to determine the phenotype of microglia
      during the acute and resolution phases of ICH in vivo and found increases in TGF
      beta1 pathway activation during the resolution phase. We then confirmed that TGF
      beta1 treatment modulated inflammatory profiles of microglia in vitro. Moreover,
      TGF-beta1 treatment following ICH decreased microglial Il6 gene expression in
      vivo and improved functional outcomes in the murine model. Finally, we observed
      that patients with early increases in plasma TGF-beta1 concentrations had better
      outcomes 90 days after ICH, confirming the role of TGF-beta1 in functional
      recovery from ICH. Taken together, our data show that TGF-beta1 modulates
      microglia-mediated neuroinflammation after ICH and promotes functional recovery,
      suggesting that TGF-beta1 may be a therapeutic target for acute brain injury.

PMID- 27893463
TI  - Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies.
AB  - The AXL receptor and its activating ligand, growth arrest-specific 6 (GAS6), are
      important drivers of metastasis and therapeutic resistance in human cancers.
      Given the critical roles that GAS6 and AXL play in refractory disease, this
      signaling axis represents an attractive target for therapeutic intervention.
      However, the strong picomolar binding affinity between GAS6 and AXL and the
      promiscuity of small molecule inhibitors represent important challenges faced by
      current anti-AXL therapeutics. Here, we have addressed these obstacles by
      engineering a second-generation, high-affinity AXL decoy receptor with an
      apparent affinity of 93 femtomolar to GAS6. Our decoy receptor, MYD1-72,
      profoundly inhibited disease progression in aggressive preclinical models of
      human cancers and induced cell killing in leukemia cells. When directly compared
      with the most advanced anti-AXL small molecules in the clinic, MYD1-72 achieved
      superior antitumor efficacy while displaying no toxicity. Moreover, we uncovered
      a relationship between AXL and the cellular response to DNA damage whereby
      abrogation of AXL signaling leads to accumulation of the DNA-damage markers
      gammaH2AX, 53BP1, and RAD51. MYD1-72 exploited this relationship, leading to
      improvements upon the therapeutic index of current standard-of-care
      chemotherapies in preclinical models of advanced pancreatic and ovarian cancer.

PMID- 27893464
TI  - The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac
      hypertrophy.
AB  - Cardiac hypertrophic growth in response to pathological cues is associated with
      reexpression of fetal genes and decreased cardiac function and is often a
      precursor to heart failure. In contrast, physiologically induced hypertrophy is
      adaptive, resulting in improved cardiac function. The processes that selectively
      induce these hypertrophic states are poorly understood. Here, we have profiled 2
      repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable
      cellular differentiation, specifically in cardiomyocytes from physiologically and
      pathologically hypertrophied rat hearts, and correlated these marks with their
      associated transcriptomes. This analysis revealed the pervasive loss of
      euchromatic H3K9me2 as a conserved feature of pathological hypertrophy that was
      associated with reexpression of fetal genes. In hypertrophy, H3K9me2 was reduced
      following a miR-217-mediated decrease in expression of the H3K9
      dimethyltransferases EHMT1 and EHMT2 (EHMT1/2). miR-217-mediated, genetic, or
      pharmacological inactivation of EHMT1/2 was sufficient to promote pathological
      hypertrophy and fetal gene reexpression, while suppression of this pathway
      protected against pathological hypertrophy both in vitro and in mice. Thus, we
      have established a conserved mechanism involving a departure of the cardiomyocyte
      epigenome from its adult cellular identity to a reprogrammed state that is
      accompanied by reexpression of fetal genes and pathological hypertrophy. These
      results suggest that targeting miR-217 and EHMT1/2 to prevent H3K9 methylation
      loss is a viable therapeutic approach for the treatment of heart disease.

PMID- 27893465
TI  - Accelerated resolution of inflammation underlies sex differences in inflammatory
      responses in humans.
AB  - BACKGROUND: Cardiovascular disease occurs at lower incidence in premenopausal
      females compared with age-matched males. This variation may be linked to sex
      differences in inflammation. We prospectively investigated whether inflammation
      and components of the inflammatory response are altered in females compared with
      males. METHODS: We performed 2 clinical studies in healthy volunteers. In 12 men
      and 12 women, we assessed systemic inflammatory markers and vascular function
      using brachial artery flow-mediated dilation (FMD). In a further 8 volunteers of
      each sex, we assessed FMD response to glyceryl trinitrate (GTN) at baseline and
      at 8 hours and 32 hours after typhoid vaccine. In a separate study in 16 men and
      16 women, we measured inflammatory exudate mediators and cellular recruitment in
      cantharidin-induced skin blisters at 24 and 72 hours. RESULTS: Typhoid vaccine
      induced mild systemic inflammation at 8 hours, reflected by increased white cell
      count in both sexes. Although neutrophil numbers at baseline and 8 hours were
      greater in females, the neutrophils were less activated. Systemic inflammation
      caused a decrease in FMD in males, but an increase in females, at 8 hours. In
      contrast, GTN response was not altered in either sex after vaccine. At 24 hours,
      cantharidin formed blisters of similar volume in both sexes; however, at 72
      hours, blisters had only resolved in females. Monocyte and leukocyte counts were
      reduced, and the activation state of all major leukocytes was lower, in blisters
      of females. This was associated with enhanced levels of the resolving lipids,
      particularly D-resolvin. CONCLUSIONS: Our findings suggest that female sex
      protects against systemic inflammation-induced endothelial dysfunction. This
      effect is likely due to accelerated resolution of inflammation compared with
      males, specifically via neutrophils, mediated by an elevation of the D-resolvin
      pathway. TRIAL REGISTRATION: ClinicalTrials.gov NCT01582321 and NRES: City Road
      and Hampstead Ethics Committee: 11/LO/2038. FUNDING: The authors were funded by
      multiple sources, including the National Institute for Health Research, the
      British Heart Foundation, and the European Research Council.

PMID- 27893468
TI  - Linear Folliculotropic CD30-Positive Lymphomatoid Drug Reaction.
AB  - We report a unique case of probable drug-induced CD30-positive lymphomatoid
      reaction. A 58-year-old woman presented with bilateral facial eruptions of 3
      weeks duration composed of erythematosus papules in a linear distribution. The
      pathological features demonstrated a dense dermal and follicular infiltrate of
      many medium- to large-sized atypical CD30-positive lymphoid cells. The rash
      resolved rapidly after discontinuation of her medication 1 week later and did not
      recur. This case highlights the importance of clinicopathological correlation.

PMID- 27893467
TI  - Bullous Pyoderma Gangrenosum With Subungual Involvement Associated With
      Ulcerative Colitis.
AB  - Pyoderma gangrenosum (PG) is a rare inflammatory and ulcerative skin disease of
      unknown etiology characterized by neutrophilic infiltration of the dermis, mainly
      affecting the lower extremities. Bullous PG is a rare variant of this disease,
      usually associated with hematologic disorders. Here, we report a case of pathergy
      positive bullous PG with subungual involvement associated with ulcerative
      colitis.

PMID- 27893466
TI  - CD30 Expression Is Rare in Myeloid Leukemia Cutis: A Study of 55 Cases and
      Implications for Routine Diagnostic Algorithms.
AB  - Expression of CD30 in blastoid cutaneous infiltrates typically signifies a CD30
      lymphoproliferative disorder, often requiring minimal immunohistochemical workup,
      if clinically consonant. However, myeloid and other hematologic malignancies
      often express CD30. We retrospectively examined the prevalence of CD30 expression
      in 41 patients (median age 59) and 55 biopsies with the diagnosis of leukemia
      cutis (LC) to determine whether an extensive immunohistochemical workup is
      warranted in all large, round cell CD30 cutaneous infiltrates. Each patient had
      refractory or recurrent disease, the histologic presence of a large mononuclear
      cell infiltrate, and varied cytogenetics. CD30 mononuclear cells within the
      infiltrate ranged from rare to many in 22 biopsies (22/55). In 18 biopsies, CD30
      cells were interpreted as lymphocytic based on morphology, strong cytoplasmic and
      Golgi staining for CD30, and negative CD34 and CD117 staining. One case showing
      3+ staining of lymphocytes was identified as a posttransplant lymphoproliferative
      disorder. The second 3+ case was favored to represent a subset of CD30-positive
      acute myeloid leukemia. Three other cases with 1+ membranous and cytoplasmic
      staining were interpreted as myeloid leukemia. In conclusion, CD30 positivity in
      myeloid leukemia in the skin is rare and does not often exhibit the strong
      membranous (2+ or 3+) and/or Golgi staining seen in reactive lymphocytes. Acute
      myeloid leukemia or myeloid LC may occasionally show 1+ (and rarely 2-3+)
      cytoplasmic/membranous or nonspecific blush nuclear CD30 labeling. Strong diffuse
      staining for CD30 should prompt consideration of a reactive
      lymphoid/lymphoproliferative process, and, when the clinical likelihood of CD30
      LC is low, may obviate the need for further immunohistochemistry.

PMID- 27893469
TI  - A Review of the Surgical Management of Extrathoracic Solitary Fibrous Tumors.
AB  - OBJECTIVES: Extrathoracic solitary fibrous tumors (ESFTs) are rare low-to
      intermediate grade spindle-cell neoplasms of pluripotent fibroblastic or
      myofibroblastic origin. This review explores prognostic factors in the management
      of ESFTs and provides guidance on optimal treatment regimens based on the current
      literature. PATIENTS AND METHODS: Electronic searches were performed using
      MEDLINE, Embase, and the Cochrane library to identify studies on prognostic
      factors in the management of ESFTs published between January 1970 and June 2016.
      The literature search and review process identified 100 articles that were
      included in this review article. This included both surgical and nonsurgical
      studies on the management of ESFTs. RESULTS: Surgical excision with wide
      resection margins forms the mainstay of treatment and provides optimal long-term
      oncological outcomes. Large tumor size (>5 to 10 cm diameter), inadequate
      resection margins, malignant histologic features, dedifferentiation, and tumor
      location within the abdomen/pelvis are associated with adverse oncological
      outcomes. Radiotherapy may be used for preoperative tumor shrinkage and/or as
      adjuvant therapy in patients with malignant disease or incomplete surgical
      margins. Chemotherapy with molecular-targeted therapies has produced promising
      results and the results of further phase 2 trials are awaited. CONCLUSIONS:
      Routine long-term follow-up is essential for benign and malignant disease to
      enable early detection and treatment of recurrent disease.

PMID- 27893471
TI  - An Oncologist's Perspective on the Affordable Care Act.

PMID- 27893472
TI  - Correspondence Between Physical Self-Concept and Participation in, and Fitness
      Change After, Biweekly Body Conditioning Classes in Sedentary Women.
AB  - Aasa, U, Paulin, J, and Madison, G. Correspondence between physical self-concept
      and participation in, and fitness change after, biweekly body conditioning
      classes in sedentary women. J Strength Cond Res 31(2): 451-461, 2017-The aims of
      the study were (a) to investigate the effects of participation in low impact body
      conditioning classes on physical fitness in sedentary women at different ages and
      (b) to examine the correspondence between physical self-concept and participation
      in, and fitness change after, the participation. Ninety-two sedentary women (mean
      age 44.2 years) participated in 11 weeks of biweekly classes that included
      cardiovascular, strength, core, endurance, and mobility exercises, all performed
      in synchrony with music. Cardiorespiratory fitness, maximal lifting strength,
      mobility, and balance tests were performed before and after the exercise period
      and the short-form of the Physical Self-Description Questionnaire (PSDQ-S) was
      completed. Zero-order Spearman correlation analyses showed that women who rated
      the PSDQ-S dimension sport competence higher participated in a larger number of
      sessions (rs = 0.24, p = 0.040). At posttests, all participants had increased
      their balance, the participants aged 20-34 years had increased their lifting
      strength, and the participants aged 35-65 years had increased their
      cardiorespiratory fitness and mobility. Most PSDQ-S dimensions did not affect
      performance change, but the perception of being physically active was related to
      increased cardiovascular fitness. We conclude that women with a sedentary
      lifestyle who wish to increase their physical capacity benefit from music
      exercise and that inquiries about perceived sport competence and physical
      activity can improve recommendations made by strength and conditioning
      professionals.

PMID- 27893470
TI  - The Association Between Out-of-Pocket Costs and Adherence to Adjuvant Endocrine
      Therapy Among Newly Diagnosed Breast Cancer Patients.
AB  - OBJECTIVE: To determine how out-of-pocket costs for adjuvant endocrine therapy
      (AET) medication affects adherence among newly diagnosed breast cancer survivors
      with private health insurance who initiate therapy. MATERIALS AND METHODS: We
      examined medical and pharmacy claims for the 1-year period after initiating AET
      using the Truven Health Analytics MarketScan database. Adherence was defined as
      >=80% proportion of days covered. Mean out-of-pocket costs for AET fill were
      measured as the sum of copayments, coinsurance, and deductibles and adjusted to
      30-day amounts. Using a multivariable logistic regression model we calculated
      adjusted risk ratios controlling for age, comorbidities, type of surgery, use of
      chemotherapy and/or radiation therapy, average out-of-pocket costs for other
      services, and pharmacy use characteristics. RESULTS: Of the 6863 women 64 years
      and younger who were diagnosed with breast cancer and initiated AET, 73.9% were
      adherent (proportion of days covered>=80%). A total of 19% of patients had <$5
      monthly out-of-pocket costs for AET, 30% had $5 to $9.99, 17% had $10 to $14.99,
      10% had $15 to $19.99, and 25% had $20 or greater. Patients with out-of-pocket
      costs for AET between $10 and $14.99, $15 and $19.99, and >$20 were 6% to 8% less
      likely to be adherent compared with patients paying <$5.00, after controlling for
      covariates (P<0.05). Out-of-pocket costs for inpatient, outpatient, and other
      pharmacy services were not associated with adherence. CONCLUSIONS: A substantial
      proportion of privately insured patients are nonadherent to AET and out-of-pocket
      costs for AET medication are significantly associated with a greater likelihood
      of nonadherence.

PMID- 27893473
TI  - Concurrent Training Promoted Sustained Anti-atherogenic Benefits in the Fasting
      Plasma Triacylglycerolemia of Postmenopausal Women at 1-Year Follow-up.
AB  - Rossi, FE, Diniz, TA, Fortaleza, ACS, Neves, LM, Picolo, MR, Monteiro, PA,
      Buonani, C, Lira, FS, and Freitas, IF Jr. Concurrent training promoted sustained
      anti-atherogenic benefits in the fasting plasma triacylglycerolemia of
      postmenopausal women at 1-year follow-up. J Strength Cond Res 32(12): 3573-3582,
      2018-The aim of this study was to compare the effects of aerobic and concurrent
      training (aerobic plus strength training) on the lipid profiles of
      normotriacylglycerolemic and hypertriacylglycerolemic postmenopausal women and to
      verify whether the benefits of aerobic and concurrent training were sustained
      after 1 year. Total cholesterol, high-density lipoprotein cholesterol (HDL-c),
      low-density lipoprotein cholesterol, triacylglycerol (TAG), and glucose were
      assessed in 46 normotriacylglycerolemic (TAG < 150 mg.dl) postmenopausal women
      divided into 3 groups: aerobic training, concurrent training (CT), and a control
      group. For CT group, hypertriacylglycerolemic postmenopausal women were recruited
      (TAG >= 150 mg.dl, n = 14). Total daily caloric consumption and free-living
      physical activity were evaluated by dietary questionnaires and accelerometer,
      respectively, and fat mass by DXA. In 16 weeks, CT was effective in increasing
      HDL-c (normotriacylglycerolemic: pre = 57.1 +/- 17.3 mg.dl * post = 64.3 +/- 16.1
      mg.dl p = 0.020 and hypertriacylglycerolemic: pre = 44.7 +/- 9.6 mg.dl * post =
      50.3 +/- 15.3 mg.dl; p = 0.012) and reducing the atherogenic index in
      normotriacylglycerolemic (pre = 3.6 +/- 0.9 mg.dl * post = 3.0 +/- 0.6 mg.dl; p =
      0.003) and hypertriacylglycerolemic (pre = 5.2 +/- 1.1 mg.dl * post = 4.7 +/- 1.2
      mg.dl; p = 0.018) postmenopausal women. In addition, the effects were sustained
      at the 1-year follow-up only among the hypertriacylglycerolemic postmenopausal
      women. The anti-atherogenic status in normotriacylglycerolemic and
      hypertriacylglycerolemic postmenopausal women was changed by CT but without
      significant differences between groups. Furthermore, these benefits are sustained
      at the 1-year follow-up among the hypertriacylglycerolemic subjects.

PMID- 27893474
TI  - Hypertrophy and Explosive-Reactive Functioning in Sedentary Men After 10 Weeks of
      Whole-Body Vibration.
AB  - Ebing, J, Gast, U, Hauptmann, C, Felsenberg, D, and Belavy, DL. Hypertrophy and
      explosive-reactive functioning in sedentary men after 10 weeks of whole-body
      vibration. J Strength Cond Res 32(1): 27-36, 2018-The objective of this study was
      to determine the impact of vertical (Power-plate; POW) and side-alternating
      (Galileo; GAL) whole-body vibration exercise on muscle mass and lower-limb
      neuromuscular function. Forty-three sedentary male subjects (18-30 year)
      randomized into 3 groups underwent 2 upper-body exercise sessions per week for 10
      weeks. Two groups of subjects underwent additional squat exercises on the GAL (N
      = 15) or POW (N = 14) devices. The third group was control. On magnetic resonance
      imaging, volume of the thigh muscles was measured. Countermovement jump, multiple
      one-leg hopping, drop jump, landing test, 15-m sprint, and grip strength were
      performed. Measurements were performed at baseline, and at 5 and 10 weeks.
      Significantly greater increases in vasti volume were seen in the GAL (+4.15%; p =
      0.00076 vs. control) and POW (+4.81%; p = 0.0074 vs. control) groups than in the
      control group (-1.22%) at 10 weeks. The adductor magnus volume increased in the
      GAL (+2.24%; p = 0.00038 vs. baseline) and POW (+2.33%; p = 0.00038 vs. baseline)
      groups at 10 weeks, but this was not significantly different from the control (
      0.67%; p = 0.54 vs. baseline). Hamstring volume decreased in GAL (-1.85%; p =
      0.00038 vs. baseline) at 5 weeks with the reduction in the POW group at 5 weeks (
      1.73%; p = 0.17 vs. baseline) not reaching significance. There were no
      significant differences between the POW and GAL groups (p >= 0.084) and no
      significant changes in neuromuscular performance. Twice weekly squat exercises
      with whole-body vibration, progressing from 3- to 5-minute time under tension,
      lead to thigh muscle hypertrophy but no improvements in explosive-reactive
      function.

PMID- 27893476
TI  - Comparison of Muscle Involvement and Posture Between the Conventional Deadlift
      and a "Walk-In" Style Deadlift Machine.
AB  - The deadlift exercise is one of the most effective exercises for developing lower
      body strength; however, technique errors can lead to low back injuries. The use
      of a "walk-in" deadlift machine removes the weight bar by using a lever system
      with independent handles on either side of the body. Theoretically, this would
      allow alignment of the load with the center of gravity, encouraging a more
      upright torso and decreasing the involvement of the low back extensors. This
      study compared trunk angle, knee angle, and electrical activity of key muscles
      between the conventional deadlift (CDL) and 2 foot positions (ball of foot or toe
      alignment) with pronated grip (called BallPro and ToePro) of a walk-in deadlift
      machine among high-skilled and low-skilled lifters. Although there were no skill
      group differences, in the combined groups, the walk-in deadlift resulted in a
      significantly more upright trunk angle (p <= 0.05) for both the BallPro (29.9
      degrees  +/- 12.0 SD) and the ToePro (32.4 degrees  +/- 10.4) compared with the
      CDL (23.7 degrees  +/- 11.3) at the start of the lift. Similar results were noted
      in the midconcentric phase, with trunk angles for the ToePro (46.9 degrees  +/-
      6.8) significantly different from CDL (42.66 degrees  +/- 3.7), and for the
      mideccentric phase of the lift, with ToePro (47.2 degrees  +/- 7.0) significantly
      higher than CDL (42.9 degrees  +/- 6.5). ToePro knee angle was significantly more
      flexed (101.6 degrees  +/- 10.6) than CDL (110.8 degrees  +/- 11.5) at the
      starting position, with both BallPro (135.7 degrees  +/- 14.2) and ToePro (136.5
      degrees  +/- 8.8) significantly more flexed than CDL (159.3 degrees  +/- 5.9) in
      both the midconcentric phase and the mideccentric phase (BallPro 129.2 degrees 
      +/- 14.0, ToePro 127.7 degrees  +/- 8.9, and CDL 150.5 degrees  +/- 7.8). In the
      combined low- and high-skilled groups, electrical activity as a percent of
      maximum isometric root mean square activity of the erector spinae during the
      BallPro variation (53.1% +/- 33.8) was significantly lower than CDL (73.19% +/-
      23.9), whereas vastus lateralis activity was significantly higher in both BallPro
      (79.9% +/- 26.3) and ToePro (64.3 +/- 22.4) compared with CDL (48.6% +/- 13.0).
      Gluteus maximus (GM) activity was significantly lower for BallPro (30.1% +/-
      16.6) and ToePro (30.2% +/- 15.0) than CDL (47.1% +/- 27.6). Together, the
      results indicate that the walk-in deadlift machine has potential to reduce the
      stress on the low back during the deadlift activity, with subjects generally
      exhibiting a more upright posture and erector spinae muscle activity, depending
      on the foot position. However, there was also a shift in muscle activity away
      from the GM and towards the knee extensors, which may limit the machine's long
      term usefulness as a deadlift replacement.

PMID- 27893477
TI  - An Evaluation of Agonist: Antagonist Strength Ratios and Posture Among
      Powerlifters.
AB  - Cutrufello, PT, Gadomski, SJ, and Ratamess, NA. An evaluation of
      agonist:antagonist strength ratios and posture among powerlifters. J Strength
      Cond Res 31(2): 298-304, 2017-Powerlifters routinely focus on 3 exercises: bench
      press, squat, and deadlift. This focus may predispose them to the development of
      muscle imbalances in either the upper or lower extremity which might also
      influence posture. Therefore, the purpose of the present study was to examine the
      agonist:antagonist strength ratios and their relationship to postural measures
      among powerlifters. An ex post facto study design compared 15 male powerlifters
      (35.3 +/- 13.7 years old) and 15 age-matched controls (34.9 +/- 14.6 years old).
      Maximal isometric strength tests were conducted using handheld dynamometry.
      Posture was evaluated using pectoralis minor length, pelvic tilt, thoracic
      kyphosis, and lumbar lordosis. Strength imbalances were observed for shoulder
      horizontal adduction:abduction (2.57 +/- 0.58 vs. 1.78 +/- 0.28; p < 0.001) and
      knee flexion:extension (0.61 +/- 0.15 vs. 0.50 +/- 0.10; p = 0.033). Pectoralis
      minor length was significantly shorter among the powerlifters (6.1 +/- 1.9 vs.
      4.2 +/- 1.4; p = 0.005); however, there was no statistical difference in thoracic
      kyphosis (37.7 +/- 9.4 vs. 39.1 +/- 10.9; p = 0.722), pelvic tilt (10.6 +/- 3.6
      vs. 11.3 +/- 3.7; p = 0.622), or lumbar lordosis (25.0 +/- 7.6 vs. 23.0 +/- 8.4;
      p = 0.500) angles. Strength imbalances, including shoulder horizontal
      adduction:abduction and knee flexion:extension, and a shortened pectoralis minor
      may evolve as training adaptations among powerlifters, whereas thoracic kyphosis,
      pelvic tilt, and lumbar lordosis remain unchanged.

PMID- 27893478
TI  - Loads and Movement Speeds Dictate Differences in Power Output During Circuit
      Training.
AB  - Power training has become a common exercise intervention for improving muscle
      strength, power, and physical function while reducing injury risk. Few studies,
      however, have evaluated acute load changes on power output during traditional
      resistance training protocols. Therefore, the aim of this study was to quantify
      the effects of different loading patterns on power output during a single session
      of circuit resistance training (CRT). Nine male (age = 19.4 +/- 0.9 years) and 11
      female participants (age = 20.6 +/- 1.6 years) completed 3 CRT protocols during
      separate testing sessions using 7 pneumatic exercises. Protocols included heavy
      load explosive contraction (HLEC: 80% one repetition maximum [1RM], maximum speed
      concentric-2 seconds eccentric), heavy load controlled contraction (HLCC: 80%
      1RM, 2 seconds concentric-2 seconds eccentric), and moderate load explosive
      contraction (MLEC: 50% 1RM, maximum speed concentric-2 seconds eccentric).
      Protocols were assigned randomly using a counterbalanced design. Power for each
      repetition and set were determined using computerized software interfaced with
      each machine. Blood lactate was measured at rest and immediately postexercise.
      For male and female participants, average power was significantly greater during
      all exercises for HLEC and MLEC than HLCC. Average power was greatest during the
      HLEC for leg press (LP), hip adduction (ADD), and hip abduction (ABD) (p <=
      0.05), whereas male participants alone produced their greatest power during HLEC
      for leg curl (LC) (p < 0.001). For male and female participants, significantly
      greater power was detected by set for LP, lat pull-down (LAT), ADD, LC, and ABD
      for the MLEC protocol (p < 0.02) and for LP, LAT, CP, and LC for the HLEC
      protocol (p < 0.03). A condition * sex interaction was seen for blood lactate
      changes ((Equation is included in full-text article.)= 0.249; p = 0.024), with
      female participants producing a significantly greater change for MLEC than HLEC
      (Mdiff = 1.61 +/- 0.35 mmol.L; p = 0.011), whereas male participants showed no
      significant differences among conditions. Performing a CRT protocol using
      explosive training patterns, especially at high loads for lower-body exercises
      and moderate loads for upper-body exercises, produces significantly higher power
      than controlled speed training in most exercises. These results provide
      exercisers, personal trainers, and strength coaches with information that can
      assist in the design of training protocols to maximize power output during CRT.

PMID- 27893480
TI  - High-Speed Resistance Training Modifies Load-Velocity and Load-Power
      Relationships in Parkinson's Disease.
AB  - Muscle power is a major neuromuscular factor affecting motor function and
      independence in patients with Parkinson's disease (PD), and it is commonly
      targeted using high-speed exercise. This study examined the changes in velocities
      (Vpp) and percent loads (%1RMpp) at peak power and load-velocity (L-V) and load
      power (L-P) relationships, resulting from resistance training because of exercise
      choice and loading in older patients with PD. Fourteen older adults with mild to
      moderate PD participated in a 12-week randomized controlled power training trial.
      Changes in L-V and L-P relationships for the biceps curl, chest press, leg press,
      hip abduction, and seated calf were assessed using pneumatic resistance machines
      at loads ranging from 30 through 90% of subjects' 1 repetition maximum for each
      exercise. Significant increases in Vpp were seen for biceps curl, leg press, hip
      abduction, and seated calf and decreases in %1RMpp were noted for biceps curl and
      hip abduction. Additionally, unique patterns of change were seen in these
      relationships across exercises, with biceps curl, chest press, and leg press
      showing the greatest shifts at the lower load end of the loading spectrum, and
      hip abduction and seated calf showing greatest responses at the higher end. The
      patterns of change in L-V and L-P relationships provide evidence for the unique
      responses of the specific muscle groups and joints to the exercises evaluated and
      offer a framework for more exacting exercise prescriptions in patients with PD.

PMID- 27893481
TI  - The Effect of Exercise-Induced Muscle Damage After a Bout of Accentuated
      Eccentric Load Drop Jumps and the Repeated Bout Effect.
AB  - Bridgeman, LA, Gill, ND, Dulson, DK, and McGuigan, MR. The effect of exercise
      induced muscle damage after a bout of accentuated eccentric load drop jumps and
      the repeated bout effect. J Strength Cond Res 31(2): 386-394, 2017-Although
      previous studies have investigated exercise-induced muscle damage (EIMD) after a
      bout of unloaded drop jumps (DJs), none have investigated the effects of
      accentuated eccentric load (AEL) DJs on EIMD. The purpose of this study was to
      investigate the effects of 30 and 50 AEL DJs on strength, jump performance,
      muscle soreness, and blood markers. Eight resistance trained athletes
      participated in this study. In week 1, baseline countermovement jump (CMJ), squat
      jump (SJ), concentric and eccentric peak force (PF), creatine kinase, and muscle
      soreness were assessed. Subjects then completed 30 AEL DJs and baseline measures
      were retested immediately postintervention, 1, 24, and 48 hours later. Two weeks
      later, the subjects completed the same protocol with an increase in AEL DJ volume
      (50). Subjects' SJ height was reduced in week 1 compared with week 3,
      postintervention, 1, 24, and 48 hours later (ES = -0.34, -0.44, -0.38, and 
      0.40). Subjects' CMJ height was reduced in week 1 compared with week 3,
      postintervention, 1, and 24 hours later (ES = -0.37, -0.29, and -0.39).
      Concentric PF was reduced in week 1 compared with week 3, postintervention and 24
      and 48 hours later (ES = -0.02, -0.23, and -0.32). Eccentric PF was reduced in
      week 1 compared with week 3, postintervention, 24, and 48 hours later (ES = 
      0.24, -0.16, and -0.50). In this sample, 30 AEL DJs attenuated the effects of
      EIMD following which 50 AEL DJs completed 2 weeks later.

PMID- 27893482
TI  - Effects of Sprint Training With and Without Weighted Vest on Speed and Repeated
      Sprint Ability in Male Soccer Players.
AB  - The purpose of this study was to assess the effect resisted sprint training using
      weighted vests (WVs) compared with unresisted sprint (US) training on physical
      fitness (countermovement jump, 10-m sprint, 30-m sprint, and repeated sprint
      ability [RSA]) in amateur male soccer players. Nineteen soccer players (age: 23.7
      +/- 4.5 years; height: 178.3 +/- 5.8 cm; body mass: 72.9 +/- 5.2 kg) were
      randomly assigned to a WV (n = 10) or a US (n = 9) group. The intervention
      program had to be performed 2 times a week over 6 weeks. The only difference
      between the 2 interventions was that the WV group performed all the sprints with
      an additional weight of 18.9% +/- 2.1% of body mass. Within-group analysis showed
      significant improvements (p < 0.001) in 10-m and 30-m sprint performances from
      pretest to posttest in WV (+9.42% and +6.04%) and US (+10.87% and +5.10%).
      Players in both WV and US also showed significant enhancements in RSA average
      time (AT), fastest time, and total time from pretest to posttest. Percentage
      changes in 30-m sprint performance, for both groups combined, had a very large
      correlation with percentage changes in AT of RSA. In the between-groups analysis,
      there were no differences between the sprint training groups (WV vs. US) in any
      variable. In conclusion, the findings of this study indicate that both sprint
      training methods used seem to be effective to improve soccer-related performance
      measures, and could be beneficial to players and coaches in field settings.

PMID- 27893483
TI  - Game Times and Higher Winning Percentages of West Coast Teams of the National
      Football League Correspond With Reduced Prevalence of Regular Season Injury.
AB  - Brager, AJ and Mistovich, RJ. Game times and higher winning percentages of west
      coast teams of the National Football League correspond with reduced prevalence of
      regular season injury. J Strength Cond Res 31(2): 462-467, 2017-West coast teams
      of the National Football League are more statistically likely to win home night
      games against east coast opponents. The alignment of game times with daily
      rhythms of alertness is thought to contribute to this advantage. This study aims
      to determine whether rates of turnovers and injuries during the regular season,
      putative measures of mental and physical fatigue, impact winning percentages.
      Regular season schedules and rates of turnovers for each of the 32 teams were
      obtained from Pro-Football-Reference. We developed our own metric of injury risk
      for each position obtained from depth charts and regular season schedules. This
      metric compared cumulative weeks on injury reserve with cumulative time zone
      travel. West coast teams traveled 4 times as often as east coast teams. However,
      teams traveling eastward won twice as many games. There was no relationship
      between the extent and direction of travel and number of turnovers. Losing teams
      had more turnovers. The offensive and defensive lines in Central Time (CT) were
      placed on injury reserve 4 times as often as offensive and defensive lines in
      Pacific Time (PT). Injury prevalence in CT vs. PT was most prominent midseason.
      Plotting midseason game time relative to biological time revealed that PT teams
      play games closer to endogenous peaks in alertness, whereas CT teams play games
      closer to endogenous troughs in alertness. Overall, closer alignment of game time
      with the endogenous "alerting" signal may protect west coast teams from fatigue
      related injuries and suggests for modified strength and conditioning programs.

PMID- 27893484
TI  - Effects of Pelvic and Core Strength Training on High School Cross-Country Race
      Times.
AB  - Clark, AW, Goedeke, MK, Cunningham, SR, Rockwell, DE, Lehecka, BJ, Manske, RC,
      and Smith, BS. Effects of pelvic and core strength training on high school cross
      country race times. J Strength Cond Res 31(8): 2289-2295, 2017-There is only
      limited research examining the effect of pelvic and core strength training on
      running performance. Pelvic and core muscle fatigue is believed to contribute to
      excess motion along frontal and transverse planes which decreases efficiency in
      normal sagittal plane running motions. The purpose of this study was to determine
      whether adding a 6-week pelvic and core strengthening program resulted in
      decreased race times in high school cross-country runners. Thirty-five high
      school cross-country runners (14-19 years old) from 2 high schools were randomly
      assigned to a strengthening group (experimental) or a nonstrengthening group
      (control). All participants completed 4 standardized isometric strength tests for
      hip abductors, adductors, extensors, and core musculature in a test-retest
      design. The experimental group performed a 6-week pelvic and core strengthening
      program along with their normal training. Participants in the control group
      performed their normal training without additional pelvic and core strengthening.
      Baseline, 3-week, and 6-week race times were collected using a repeated measures
      design. No significant interaction between experimental and control groups
      regarding decreasing race times and increasing pelvic and core musculature
      strength occurred over the 6-week study period. Both groups increased strength
      and decreased overall race times. Clinically significant findings reveal a 6-week
      pelvic and core stability strengthening program 3 times a week in addition to
      coach led team training may help decrease race times.

PMID- 27893487
TI  - Radial Extracorporeal Shock Wave Therapy Is Effective and Safe in Chronic Distal
      Biceps Tendinopathy.
AB  - OBJECTIVE: To assess the efficacy and safety of radial extracorporeal shock wave
      therapy (rESWT) for chronic distal biceps tendinopathy (cDBT). DESIGN: Case
      control study (level of evidence, 3). SETTING: SUN Orthopaedics and Sports
      Medicine. PATIENTS: Patients with a diagnosis of cDBT were recruited between
      January 2010 and February 2015. INTERVENTIONS: Patients received a single session
      of rESWT (2000 shock waves with energy flux density of 0.18 mJ/mm) or other forms
      of nonoperative therapy. MAIN OUTCOME MEASURES: Patients completed the visual
      analog scale (VAS), the modified QuickDASH (MQD) score, and the Roles and
      Maudsley (RM) score over a 12-month period. RESULTS: Forty-eight patients
      completed the final review at 12 months and were included in the study. Subjects
      ranged in age from 30 to 64 years. Mean pretreatment VAS scores for the rESWT and
      control groups were 8.3 and 8.5, respectively. Three and 12 months after
      inclusion in the study, the mean VAS scores for the rESWT and control groups were
      3.4 and 5.6 (P < 0.001) and 2.7 and 4.7 (P < 0.001), respectively. Twelve-month
      follow-up MQD-Sports and MQD-Work scores for the rESWT and control groups were
      3.7 and 1.7 (P < 0.001) and 3.8 and 1.8 (P < 0.001), respectively. Differences in
      mean RM scores were statistically significant between groups at 3 months after
      the treatment. There were no significant complications. CONCLUSIONS: Overall,
      rESWT is an effective and safe treatment for cDBT. CLINICAL RELEVANCE: Radial
      ESWT as a novel, effective, and safe treatment for cDBT.

PMID- 27893486
TI  - Rankings of High School Sports Injury Rates Differ Based on Time Loss
      Assessments.
AB  - OBJECTIVE: To examine how injury definition inclusiveness affects the rank order
      of injury rates in 27 high school (HS) sports. DESIGN: The National Athletic
      Treatment, Injury and Outcomes Network (NATION) used certified athletic trainers
      (ATs) to collect injury and athlete-exposure (AE) data in practices and
      competitions for 27 HS sports during the 2011/2012 to 2013/2014 academic years.
      Time loss (TL) injuries resulted in >=24 hours of participation restriction.
      Nontime loss (NTL) injuries resulted in <24 hours of participation restriction.
      SETTING: Aggregate injury and exposure data collected from 27 HS sports.
      PARTICIPANTS: High school student-athletes. INTERVENTIONS: Sports injury data
      from the National Athletic Treatment, Injury and Outcomes Network. MAIN OUTCOME
      MEASURES: Time loss and TL + NTL injury rates were calculated. Sport-specific
      rates were placed in rank order, stratified by gender. RESULTS: Most of the 47
      014 injuries reported were NTL (82.8%). Among boys' sports, TL injury rates were
      greatest in football (3.27/1000AE) and wrestling (2.43/1000AE); TL + NTL injury
      rates were greatest also in football (15.29/1000AE) and wrestling (11.62/1000AE).
      Among girls' sports, TL injury rates were greatest in soccer (1.97/1000AE) and
      basketball (1.76/1000AE); TL + NTL injury rates were greatest in field hockey and
      lacrosse (both 11.32/1000AE). CONCLUSIONS: The rank order of injury rates and the
      resulting injury prevention priorities may depend on injury definition
      inclusiveness, particularly in female HS sports.

PMID- 27893485
TI  - Peripheral neuropathic pain: a mechanism-related organizing principle based on
      sensory profiles.
AB  - Patients with neuropathic pain are heterogeneous in etiology, pathophysiology,
      and clinical appearance. They exhibit a variety of pain-related sensory symptoms
      and signs (sensory profile). Different sensory profiles might indicate different
      classes of neurobiological mechanisms, and hence subgroups with different sensory
      profiles might respond differently to treatment. The aim of the investigation was
      to identify subgroups in a large sample of patients with neuropathic pain using
      hypothesis-free statistical methods on the database of 3 large multinational
      research networks (German Research Network on Neuropathic Pain (DFNS), IMI
      Europain, and Neuropain). Standardized quantitative sensory testing was used in
      902 (test cohort) and 233 (validation cohort) patients with peripheral
      neuropathic pain of different etiologies. For subgrouping, we performed a cluster
      analysis using 13 quantitative sensory testing parameters. Three distinct
      subgroups with characteristic sensory profiles were identified and replicated.
      Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in
      combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia,
      33%) was characterized by preserved sensory functions in combination with heat
      and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3
      (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber
      function in combination with pinprick hyperalgesia and dynamic mechanical
      allodynia. All clusters occurred across etiologies but frequencies differed. We
      present a new approach of subgrouping patients with peripheral neuropathic pain
      of different etiologies according to intrinsic sensory profiles. These 3 profiles
      may be related to pathophysiological mechanisms and may be useful in clinical
      trial design to enrich the study population for treatment responders.

PMID- 27893489
TI  - Military Service and Amyotrophic Lateral Sclerosis in a Population-based Cohort:
      Extended Follow-up 1979-2011.

PMID- 27893488
TI  - Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five
      African Countries.
AB  - BACKGROUND: Understanding associations between pregnancy and HIV disease
      progression is critical to provide appropriate counseling and care to HIV
      positive women. METHODS: From 2006 to 2011, women less than age 40 with incident
      HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda,
      South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated
      associations between pregnancy and HIV disease progression. Clinical progression
      was defined as a single CD4 measurement <200 cells/MUl, percent CD4 <14%, or
      category C event, with censoring at antiretroviral (ART) initiation for reasons
      other than prevention of mother-to-child transmission (PMTCT). Immunologic
      progression was defined as two consecutive CD4s <=350 cells/MUl or a single CD4
      <=350 cells/MUl followed by non-PMTCT ART initiation. Generalized estimating
      equations assessed changes in CD4 before and after pregnancy. RESULTS: Among 222
      women, 63 experienced clinical progression during 783.5 person-years at risk
      (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1
      person-years at risk (12.8/100). The association between pregnancy and clinical
      progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI):
      0.2, 1.8. The association between pregnancy and immunologic progression was aHR =
      1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles
      A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before
      versus after pregnancies were not different. CONCLUSIONS: In this cohort,
      pregnancy was not associated with increased clinical or immunologic HIV
      progression. Similarly, we did not observe meaningful deleterious associations of
      pregnancy with CD4s. Our findings suggest that HIV-positive women may become
      pregnant without harmful health effects occurring during the pregnancy.
      Evaluation of longer-term impact of pregnancy on progression is warranted.

PMID- 27893490
TI  - Total Wrist Arthrodesis: Indications and Clinical Outcomes.
AB  - Total wrist arthrodesis remains an important technique in the surgical
      armamentarium of upper extremity surgeons. The procedure has evolved over time
      but continues to provide reliable pain relief at the expense of wrist motion. It
      is indicated for management of a wide variety of upper extremity conditions,
      including rheumatoid arthritis, posttraumatic osteoarthritis, cerebral palsy, and
      brachial plexus injuries, and as a salvage technique after failed implant
      arthroplasty. Recent studies demonstrate high levels of patient satisfaction and
      good functional outcomes after bilateral wrist fusion. Compared with total wrist
      arthroplasty, total wrist arthrodesis provides more reliable pain relief with
      lower rates of complications, but further studies are needed to compare
      functional outcomes and cost-effectiveness.

PMID- 27893491
TI  - Role of low-molecular-weight heparins in prevention of thromboembolic
      complication after transarterial chemoembolization in hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication after
      transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). This is
      the first clinical study to evaluate the role of low-molecular-weight heparins
      (LMWHs) with TACE in HCC for the prevention of thromboembolism complications
      (PVT). PATIENTS AND METHODS: This study was carried out on 40 patients with HCC
      requiring TACE who presented to the Tropical Medicine Department, Tanta
      University and Interventional Radiology Department of Ain-Shams University
      Hospitals starting from April 2015. Patients were divided in two groups: group I
      included 20 patients with HCC treated by TACE only. Group II included 20 patients
      with HCC treated by TACE and an adjuvant dose of LMWH. Radiological assessment of
      efficacy of procedure and detection of PVT as a complication was performed using
      ultrasound abdomen and pelvis and triphasic spiral computed tomography with
      contrast. RESULTS: This study was carried out on 40 patients with HCC requiring
      TACE who presented to the Tropical Medicine Department of Tanta University and
      Interventional Radiology Department of Ain-Shams University Hospitals. The
      incidence of PVT after TACE was higher in group I than group II, with seven cases
      in group I and only one case in group II. CONCLUSION: LMWH with TACE in HCC is
      strongly recommended for prevention of thromboembolism complications (PVT).
      However, larger randomized-controlled studies are needed to confirm these obvious
      findings.

PMID- 27893492
TI  - Safety of Local Intracutaneous Lidocaine Anesthesia Used by Dermatologic Surgeons
      for Skin Cancer Excision and Postcancer Reconstruction: Quantification of
      Standard Injection Volumes and Adverse Event Rates.
AB  - BACKGROUND: Intracutaneous lidocaine is used for anesthesia in dermatologic
      surgery for skin cancer excision and repair with exceedingly low incidence of
      reported adverse events. OBJECTIVE: To measure (1) the quantity of lidocaine
      typically used for facial skin cancer excision and reconstruction; and (2) the
      frequency and character of associated adverse events. METHODS: Survey study of
      dermatologic surgeons with longitudinal reporting. Reported practice during 10
      business days: (1) mean volume of 1% lidocaine per skin cancer excision; (2)
      maximum per excision; (3) mean per reconstruction; and (4) maximum per
      reconstruction. RESULTS: A total of 437 of 1,175 subjects contacted (37.2%)
      responded. Mean per excision was 3.44 mL (SD: 2.97), and reconstruction 11.70 mL
      (10.14). Maximum per excision was 6.54 mL (4.23), and reconstruction was 15.85 mL
      (10.39). No cases of lidocaine toxicity were reported, diagnosed, or treated.
      Incidence of adverse events possibly anesthesia related was >0.15%, with most
      (0.13%) being mild cases of dizziness, drowsiness, or lightheadedness from
      epinephrine tachycardia. CONCLUSION: Toxicity associated with local anesthesia
      other than lidocaine was not studied. Volumes of lidocaine in skin cancer
      excision and repair are modest and within safe limits. Lidocaine toxicity is
      exceedingly rare to entirely absent. For comparable indications, lidocaine is
      safer than conscious sedation or general anesthesia.

PMID- 27893493
TI  - Improving Detection of Iron Deposition in Cirrhotic Liver Using Susceptibility
      Weighted Imaging With Emphasis on Histopathological Correlation.
AB  - OBJECTIVE: The aim of this study was to investigate the value of susceptibility
      weighted imaging (SWI) for detection and quantification of iron deposition in
      cirrhotic liver. METHODS: Fifty-five cirrhotic patients underwent hepatic
      magnetic resonance imaging examination including SWI and multiecho T2*-weighted
      imaging (T2*WI). Detection of iron deposition and number of siderotic nodules
      were compared between SWI and T2*WI. Correlation among SWI phase value, T2*
      value, and hepatic iron concentration were determined. RESULTS: Susceptibility
      weighted imaging significantly improved detection of iron deposition compared
      with T2*WI (90.7% vs 66.7%, P = 0.002), attributing to grade 1 (73.3% vs 26.7%, P
      = 0.027) and grade 2 (93.8% vs 56.3%, P = 0.037). Iron deposition of grade 3 and
      4 could be detected by both SWI and T2*WI. The number of siderotic nodules
      visualized on SWI was significantly larger than that on T2*WI (107.5 +/- 7.4 vs
      62.7 +/- 4.6, P = 0.002). There were significantly negative correlation between
      phase value and iron score (r = -0.803), and positive correlation between phase
      value and T2* value (r = 0.771). CONCLUSIONS: Susceptibility-weighted imaging can
      improve detection of minimal and mild iron deposition in cirrhotic liver.

PMID- 27893494
TI  - A Comparison of Magnetic Resonance Imaging and Electroneuromyography for
      Denervated Muscle Diagnosis.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic value of magnetic
      resonance imaging (MRI) for muscle denervation due to focal lesions of the median
      nerve and to compare electrophysiological findings with MRI findings. METHODS:
      Twenty-six patients with electrophysiological studies diagnosed for focal lesions
      of the median nerve were included in this study. Electrophysiological studies and
      MRI were conducted on 34 patients' hands. Patients' hands were divided into two
      groups based on edema findings revealed by the MRI: group 1 (edema-negative
      group; n = 24) and group 2 (edema-positive group; n = 10). RESULTS: Positive
      correlations were found between the existence of edema in MRI and fibrillation,
      positive sharp waves, denervation, and the level of reduced recruitment pattern.
      In median nerve conduction studies, amplitude of compound muscle action potential
      and palm-to-wrist segment mixed-nerve action potentials were significantly lower,
      and also the third-digit wrist sensory nerve conduction velocity and mixed-nerve
      palm-wrist conduction velocity were significantly slower in group 2. CONCLUSIONS:
      For muscle denervation resulting from median nerve lesions, MRI findings
      correlated with electrophysiological findings; further study is required for the
      use of MRI.

PMID- 27893495
TI  - Integration of EEG Into Psychiatric Practice: A Step Toward Precision Medicine
      for Autism Spectrum Disorder.
AB  - INTRODUCTION: Data from an EEG is not commonly used by psychiatrists to plan
      treatment and medication. However, EEG abnormalities such as isolated
      epileptiform discharges are found to be more prevalent in psychiatric patients,
      particularly those diagnosed with autism spectrum disorder (ASD). Most
      medications prescribed for ASD lower seizure threshold and increase side effects.
      Therefore, it may be prudent to order an EEG for ASD cases, especially those
      categorized as refractory. METHODS: The data set was obtained from a
      multidisciplinary practice that treats a wide variety of neuroatypical children
      and adolescent refractory patients. This study investigated 140 nonepileptic
      subjects diagnosed with ASD, aged 4 to 25 years. Visual inspection of the EEG was
      performed to search for paroxysmal, focal, or lateralizing patterns. RESULTS: Of
      the 140 subjects, the EEG data identified 36% with isolated epileptiform
      discharges. The chi analysis found no significant difference between genders
      among the three age groups. Findings indicated a high prevalence of isolated
      epileptiform discharges among individuals with ASD. CONCLUSIONS: Our results find
      that compared with the healthy population, a large number of patients with ASD
      have isolated epileptiform discharges despite never having a seizure. Our
      findings support the use of EEG in children, adolescents, and young adults with
      ASD, regardless of gender or age. This is particularly true for those who exhibit
      aggressive behaviors or those who have failed previous medication attempts with
      stimulants, antidepressants, and/or antipsychotics.

PMID- 27893496
TI  - Do Leadership Style, Unit Climate, and Safety Climate Contribute to Safe
      Medication Practices?
AB  - OBJECTIVES: This study aims at: examining if leadership style and unit climate
      predict safety climate; and testing the direct, indirect, and total effect of
      leadership style, unit climate, and safety climate on nurses' safe medication
      practices. BACKGROUND: The Institute of Medicine and nursing scholars propose
      that safety climate is a prerequisite to safety practices. However, there is
      limited empirical evidence about factors contributing to the development of
      safety climate and about the association with nurses' safe medication practices.
      METHOD: This cross-sectional study used survey data from 246 RNs working in a
      Magnet(r) hospital. RESULTS: Leadership style and unit climate predicted 20% to
      50% of variance on all safety climate dimensions. Model testing revealed the
      indirect impact of leadership style and unit climate on nurses' safe medication
      practices. CONCLUSION: Our hypothesized model explained small amount of the
      variance on nurses' safe medication practices. This finding suggests that nurses'
      safe medication practices are influenced by multiple contextual and personal
      factors that should be further examined.

PMID- 27893497
TI  - Nurse Managers Speak Out About Disruptive Nurse-to-Nurse Relationships.
AB  - OBJECTIVE: The purpose of this study is to explore nurse managers' (NMs')
      perceptions regarding disruptive nurse-to-nurse relationships. BACKGROUND: Nurse
      managers play a pivotal role in creating and sustaining healthy practice
      environments. They must understand how to recognize and confront disruptive nurse
      relationships that can threaten the health of their units. METHODS: A qualitative
      study design using researcher-participant interviews of 13 NMs from 5
      institutions provided data regarding NMs' views on nurse relationships. RESULTS:
      Nurse managers reported how they became aware of disruptive nurse relationships,
      their strategies for dealing with those relationships, and the impact that
      confronting disruptive relationships had on them personally. CONCLUSION: Findings
      can be helpful to NMs who are faced with addressing disruptive nurse-to-nurse
      relationships as they endeavor to create and sustain healthy work environments.

PMID- 27893498
TI  - Wired to the Workplace: The Relationship Between Electronic Connectedness to Work
      and Nurse Manager Satisfaction.
AB  - OBJECTIVE: The aim of this study is to describe the beliefs and behaviors of
      nurse leaders regarding electronic connectedness with their workplace and
      workplace support. BACKGROUND: Electronic communication enables leaders'
      continuous availability to the workplace. This may blur home-work boundaries and
      contribute to burnout. METHODS: This mixed-methods study surveyed nurses in 6
      acute care hospitals in north Texas. A qualitative phase employed focus groups
      composed of nurses from participating hospitals to validate and enrich data
      collected in the quantitative phase. RESULTS: Data showed that leader support
      directly influenced work-related electronic communication by influencing
      expectations regarding connectedness. Furthermore, leaders who frequently thought
      of leaving employment reported significantly lower levels of supervisor support
      and stronger beliefs that work interfered with home life than other respondents
      did. Focus group data supported survey findings. CONCLUSIONS: Electronic
      availability of nurse leaders did not directly affect satisfaction, but
      supervisor support and perception that work interferes with home life strongly
      and directly affected satisfaction.

PMID- 27893499
TI  - The Role of the Nurse Executive in Rural Hospital Closure.
AB  - Between 2010 and June 2016, 75 rural hospitals closed, and more than 250 more are
      at risk of closure. Nurse executives need to be prepared for this eventuality.
      There is a need for formal direction on how to close a highly regulated
      healthcare facility.

PMID- 27893501
TI  - Foreword.

PMID- 27893500
TI  - The Effect of Reported Sleep, Perceived Fatigue, and Sleepiness on Cognitive
      Performance in a Sample of Emergency Nurses.
AB  - OBJECTIVE: The aim of this study is to explore the relationship between reported
      sleep, perceived fatigue and sleepiness, and cognitive performance. BACKGROUND:
      Although evidence suggests that fatigue and sleepiness affect the provision of
      care in inpatient units, there is a lack of research on the sleep patterns of
      emergency nurses and the effects of disturbed sleep and fatigue on their
      cognitive abilities and susceptibility to medical errors. METHODS: A quantitative
      correlational design was used in this study; in each of 7 different statistical
      models, zero-order relationships between predictors and the dependent variable
      were examined with appropriate inferential tests. RESULTS: Participants reported
      high levels of sleepiness and chronic fatigue that impeded full functioning both
      at work and at home. CONCLUSIONS: Although high levels of self-reported fatigue
      did not show any effects on cognitive function, other factors in the environment
      may contribute to delayed, missed, or inappropriate care. Further research is
      indicated.

PMID- 27893502
TI  - Implementing a 4C Approach to Quality Improvement.
AB  - Designing a quality improvement activity can be labor intensive and intimidating
      to facilitators who have not been specially trained in process improvement
      methodologies. To simplify the process, a team was formed with the specific task
      of developing a basic model that addresses key concepts in change theory. The
      2010 Institute of Medicine report stresses the importance of health care
      professionals working together, collaboratively, to use data to improve patient
      outcomes and improve care nationally. In addition, as noted in Quality and Safety
      Education for Nurses (2013), competencies have been developed to promote
      frontline problem solving including using data for quality improvement, providing
      safe care, functioning in collaborative teams, respecting and addressing patient
      and family concerns, applying evidence-based practice, and using informatics to
      make decisions. The team completed a search of the literature on change theory to
      identify the factors that are imperative to address when initiating a process
      improvement cycle. Kotter's Model of Change provided direction and guidance on
      the creation of the 4C model, which involves centering on issue, collaborating
      with team members, using the change process, and celebrating successes. This
      model has been implemented in a multihospital system as a framework for process
      improvement with such initiatives as preventing hospital-acquired infections,
      implementing patient safety initiatives, and addressing human resource concerns
      such as turnover and patient satisfaction.

PMID- 27893503
TI  - Impacting Care and Treatment of the Burn Patient Conversion to Electronic
      Documentation.
AB  - Improving patient care through enhanced electronic communication among health
      care providers is aimed at reducing the number of medication and medical errors.
      The American Reinvestment and Recovery Act (ARRA) was signed into law in 2009,
      supporting the federal government's commitment to the improvement of health care
      quality, safety, and efficiency through requirements to implement an electronic
      health record by October 2015 or hospitals and eligible providers potentially
      realizing penalties or reduced reimbursement rates. In addition to ARRA, Congress
      presented another initiative to further advance the delivery of high-quality
      health care, the Health Information Technology for Economic and Clinical Health
      Act (HITECH), leading to the authorization of $27 billion to encourage health
      care providers to achieve meaningful use of the electronic health record.
      However, the conversion of the paper medical records to an electronic version has
      been challenging, particularly in specialty departments. The burn unit of a
      tertiary hospital located in the Pittsburgh area experienced such challenges. A
      project plan, developed in 2009 prior to the electronic medical record going
      live, involved a multidisciplinary team, consisting of providers, nurses, and
      information system builders who came together to determine how to capture the
      totality of the burn unit documentation. The goal of the project was to develop
      an electronic documentation tool and provide a system to accurately and
      efficiently evaluate documentation compliance with the staff. The Lund Browder
      documentation tool, used with the paper medical record, was the selected tool for
      the electronic conversion. This tool has been regarded by most health care
      organizations as being the most accurate in measuring the extent and degree of
      the burn. With the paper documentation tool, the staff was, on average, 74%
      compliant with the Lund Browder tool. The electronic version and availability of
      the tool increased compliance to 100% in the fourth quarter of 2015.

PMID- 27893504
TI  - Accurate Identification of Infection Source in Burn Trauma Patients With Central
      Line Infection to Determine Appropriate Treatment Option As Well As Proper Public
      Reporting.
AB  - With the advent of the Patient Safety Movement in the late 1990s and the CMS
      (Centers for Medicare & Medicaid Services) nonreimbursement program for never
      events, there has been much focus on the prevention and accurate identification
      of health care-associated infections such as central line-associated bloodstream
      infections (CLABSIs). There has certainly been a national effort to decrease the
      occurrence of these infections. With the implementation of patient safety
      initiatives such as the central line prevention bundle, there has been a
      considerable reduction in the number of CLABSIs except for patients with burn
      trauma. Because of the compromised nature of these patients, the number of
      CLABSIs has not decreased similarly to other types of patients. In addition,
      these patients may have a secondary infection that was not accurately or timely
      identified. With CLABSIs, proper identification of primary and secondary
      infections is very important, particularly when identifying treatment options and
      ensuring accurate public reporting of health care-associated infection
      information.

PMID- 27893505
TI  - Rib Fracture Protocol Advancing the Care of the Elderly Patient.
AB  - This article discusses unique factors associated with rib fractures in the
      elderly patient population and explains the process used in one facility to
      develop a revised protocol for the management of elderly patients with a rib
      fracture. The goals were to eliminate gaps in early trauma care management and
      employ a care routine that would improve outcomes for this vulnerable group of
      patients with fracture.

PMID- 27893507
TI  - Case Study: Obstetrical Trauma With Maternal Death and Fetal Survival.
AB  - Trauma during pregnancy is the leading cause of non-obstetric-related maternal
      and fetal death. This article summarizes obstetric physiology and outlines the
      assessment and treatment of traumatic injuries of the pregnant patient. A case is
      presented in which a pregnant woman with blunt abdominal trauma was managed
      efficiently in a trauma center within a hospital that does not have in-house
      obstetric services.

PMID- 27893506
TI  - The Hospital Course of a Successfully Treated Patient with Respiratory Failure:
      Beginning to End!
AB  - The successful treatment of a patient with acute respiratory failure is a complex
      undertaking that requires clinical competence, evidence-based interventions,
      seamless coordination of care transitions, and transparent open communication
      among all members of the health care team. Many of the processes of care in these
      critically ill patients are reassuringly consistent across services, across
      hospitals, across health systems, and even across the country. Although the
      clinical course of such complicated patients can be extremely unpredictable, we
      are fortunate that the professional, technical, and psychosocial aspects of care
      for these patients can be relatively orderly, evidence-based, and transparent.

PMID- 27893509
TI  - Educating Providers in Return-to-Play Suggested Guidelines Postconcussion.
AB  - As the awareness of concussions increases, it is imperative to be able to
      evaluate, diagnose, and treat concussed individuals properly to prevent further
      complications or death. The primary purpose of this study was to compare a
      provider's current awareness and comfort level as it relates to the return-to
      play guidelines for concussions. A secondary aim was to evaluate current
      protocols that are in use and determine whether they coincide with the suggested
      guidelines. An educational intervention was implemented to assess the knowledge
      and confidence of health care providers. The study design was a quantitative,
      convenient sample, pretest/posttest questionnaire. The questionnaire was
      administered to participants who were nurse practitioners prior to an educational
      PowerPoint presentation. At 8 weeks, the posttest was administered. Approximately
      19% of individuals were not aware of a graded return-to-play protocols. The
      findings suggest that the educational intervention increased their confidence
      levels in making a diagnosis of a concussion, in assessing danger signs, and in
      understanding when to refer to a specialist. Additional supporting evidence from
      this study indicates that the educational intervention allowed the participants
      to achieve a greater comfort level in finding appropriate resources for them and
      their patients.

PMID- 27893508
TI  - Best Practices for Pressure Ulcer Prevention in the Burn Center.
AB  - The State of Pennsylvania Hospital Engagement Network, in collaboration with a
      hospital system in Southwestern Pennsylvania, established a goal of reducing
      hospital-acquired pressure ulcers by 20%. A 6-month unfavorable trend of nurse
      sensitive clinical indicators called for immediate process improvement. A
      retrospective chart review resulted in identification of predominant risk factors
      placing the burn patient at high risk for pressure ulcer formation.
      Implementations of pressure ulcer prevention measures were inconsistent. Nurses
      demonstrated varied levels of knowledge about products used for prevention. It
      became imperative to examine processes within the unit and provide nursing with
      education, access to skin care supplies, and advanced skin/wound care products
      for maintaining skin integrity. Creation of evidence-based guidelines was
      necessary to improve patient outcomes. A collaborative team approach influenced
      nursing and physician awareness of pressure ulcer risk. Evidence-based prevention
      guidelines were developed, and consistency in early intervention was achieved,
      supporting our culture of safety. A change in interprofessional collaborative
      practice and positive trend in pressure ulcer incidence data supports the success
      of our program.

PMID- 27893510
TI  - Preparing Critical Care and Medical-Surgical Nurses to Open a New Hospital.
AB  - Building a new hospital is an exciting time. However significant planning is
      required to prepare staff to assume care of patients in an environment with new
      workflow changes and new equipment. The challenges of this advanced preparation
      are compounded when the opening of the new hospital includes the planned move of
      the inpatient census of patients from an existing hospital to the new hospital.
      Goals and objectives on the move day include patient and staff safety, with a
      seamless transition to the new environment. This article describes the
      experiences and strategies used by an adult inpatient department to successfully
      open a new hospital.

PMID- 27893512
TI  - Flap Designs for Flap Advancement During Implant Therapy: A Systematic Review.
AB  - PURPOSE: Guided bone regeneration (GBR) procedures allow ridge augmentation
      before or at time of implant placement. GBR outcomes rely on primary passive
      tension-free wound closure, which may be achieved by a variety of flap designs
      and surgical procedures. A comprehensive literature review of flap design and
      management is provided, including material types, incision design, reflection,
      releasing, and suturing techniques. MATERIALS AND METHODS: Two reviewers
      completed a literature search using the PubMed database and a manual search of
      relevant journals. Relevant articles from January 1990 to September 2015
      published in the English language were considered. RESULTS: A variety of flap
      designs aim to achieve primary passive closure during GBR were introduced. To
      facilitate case selection and treatment planning, flap designs have been
      categorized based on their ability to achieve minor (<3 mm), moderate (3-6 mm),
      and major (>=7 mm) degrees of flap advancement. CONCLUSIONS: Techniques such as
      vertical releasing incisions, periosteal releasing incisions, and split-thickness
      flaps may be used alone or combined to achieve passivity during GBR. GBR
      complications may be prevented by imaging and preoperative planning and careful
      surgical technique especially flap advancement.

PMID- 27893511
TI  - Continuous Infusion Antiepileptic Medications for Refractory Status Epilepticus:
      A Review for Nurses.
AB  - Status epilepticus requires treatment with emergent initial therapy with a
      benzodiazepine and urgent control therapy with an additional antiepileptic drug
      (AED) to terminate clinical and/or electrographic seizure activity. However,
      nearly one-third of patients will prove refractory to the aforementioned
      therapies and are prone to a higher degree of neuronal injury, resistance to
      pharmacotherapy, and death. Current guidelines for refractory status epilepticus
      (RSE) recommend initiating a continuous intravenous (CIV) anesthetic over bolus
      dosing with a different AED. Continuous intravenous agents most commonly used for
      this indication include midazolam, propofol, and pentobarbital, but ketamine is
      an alternative option. Comparative studies illustrating the optimal agent are
      lacking, and selection is often based on adverse effect profiles and patient
      specific factors. In addition, dosing and titration are largely based on small
      studies and expert opinion with continuous electroencephalogram monitoring used
      to guide intensity and duration of treatment. Nonetheless, the doses required to
      halt seizure activity are likely to produce profound adverse effects that
      clinicians should anticipate and combat. The purpose of this review was to
      summarize the available RSE literature focusing on CIV midazolam, pentobarbital,
      propofol, and ketamine, and to serve as a primer for nurses providing care to
      these patients.

PMID- 27893513
TI  - Schneiderian Membrane Perforation Rate and Increase in Bone Temperature During
      Maxillary Sinus Floor Elevation by Means of Er: YAG Laser-An Animal Study in
      Pigs.
AB  - PURPOSE: To assess the time of preparation, bone temperature increase, and the
      Schneiderian membrane perforation rate during maxillary sinus floor elevation.
      MATERIALS AND METHODS: The research included 30 maxillary sinuses (n = 30) of a
      pig, divided into 2 groups (n = 15). The lateral bony windows were created using
      Er:YAG laser (200 mJ, 15 Hz, energy density: 25.48 J/cm) and a diamond bur
      (control). The membrane was elevated using laser (50 mJ, 50 Hz) and hand
      instruments. The bone temperature was measured by K-type thermocouple. RESULTS:
      Significantly lower rates of the Schneiderian membrane perforation were found in
      the laser group (6.67%) compared with the bur (33%) (P < 0.05). The significant
      higher increase in temperature (mean 7.6 degrees C) was found in the experimental
      group as compared with the control group (mean 2 degrees C) (P = 0.0000033). The
      average time necessary for the laser bony window osteotomy was 10 minutes and 37
      seconds, whereas using the bur required middling 5 minutes and 50 seconds (P =
      0.000283). CONCLUSION: The application of Er:YAG laser may significantly reduce
      the risk of iatrogenic perforation of the Schneiderian membrane and does not
      cause an irreversible thermal damage in a pig model.

PMID- 27893514
TI  - Improved Bone Regeneration With Multiporous PLGA Scaffold and BMP-2-Transduced
      Human Adipose-Derived Stem Cells by Cell-Permeable Peptide.
AB  - OBJECTIVE: Currently, much work has focused on the engineering of bone using
      adipose-derived stem cells (ADSCs), which differentiate into osteogenic cells.
      This study was conducted to assess the bone-regenerating capacity of ADSCs with
      genetic modification. MATERIALS AND METHODS: ADSCs were cultured and transduced
      with recombinant adenovirus-expressing bone morphogenetic protein-2 (rAd/BMP-2).
      Two 5-mm full-thickness bone defects were created on the parietal bones of 24
      rats. The defects were left empty (n = 12), restored with a scaffold alone (n =
      12), transplanted with ADSCs in osteogenic media (n = 12), or transplanted with
      rAd/BMP-2-transduced ADSCs (n = 12). Six defects from each group were assessed by
      histologic observation, histomorphometric analysis, and microcomputed tomography
      (micro-CT) imaging at 4 and 8 weeks after transplantation. RESULTS: Increased new
      bone formation was observed in the rAd/BMP-2-transduced ADSC groups, compared
      with the other groups. On micro-CT, significant differences were noted in bone
      volume-to-tissue volume ratios between rAd/BMP-2-transduced ADSCs group and the
      other groups at both time points (P < 0.05). CONCLUSION: The result demonstrates
      that transferring BMP-2 promotes the osteogenic differentiation of ADSCs and
      enhances bone regeneration. Under limitation of this study, genetic modification
      of ADSCs with BMP-2 could be adopted in clinical application.

PMID- 27893516
TI  - Caregiver Expectations and Satisfaction of Urgent Care in a Pediatric Emergency
      Department.
AB  - Health care delivery expectations that may affect patient and caregiver
      satisfaction are not clearly understood. This study examined caregiver
      expectations and satisfaction with urgent care in a pediatric emergency
      department. Of 201 caregivers surveyed, we found that caregivers have specific
      expectations regarding clinical care of their child in terms of radiographic
      imaging, blood testing, antibiotics, pain management, and subspecialty
      consultation. Caregivers were generally less dissatisfied with the actual care
      provided than the urgent care physicians expected.

PMID- 27893515
TI  - Use of Federally Qualified Health Centers and Potentially Preventable Hospital
      Utilization Among Older Medicare-Medicaid Enrollees.
AB  - Using Medicare claims data from 2007 to 2010, we sought to determine whether dual
      eligibles 65 years and older who utilize federally qualified health centers
      (FQHCs) have lower rates of ambulatory care-sensitive hospitalizations and
      emergency department visits compared with nonusers. We found that FQHC use is
      associated with increased ambulatory care-sensitive hospitalization rates for
      whites and other races, but a decrease among blacks. Depending on race, FQHC use
      is associated with an increase of 24 to 43 ambulatory care-sensitive emergency
      department visits per thousand persons annually. More research is needed to
      understand why FQHC use is associated with these outcomes among dual eligibles.

PMID- 27893517
TI  - Ready for Change? The Role of Physician and Staff Engagement, Burnout, and
      Workplace Attributes.
AB  - We examined factors associated with change readiness among 343 primary care
      physicians and 590 nonphysician staff undergoing "Lean"-based process
      improvements. Baseline levels of engagement were associated with greater
      readiness for change across all measured domains. Job-related burnout correlated
      with greater need for change, but lower self-efficacy and perceived support,
      whereas a personal sense of accomplishment was associated with higher efficacy to
      implement changes. At a department level, teamwork, participation in decision
      making, and change history were associated with higher engagement and lower
      burnout among physicians and staff; conversely, a busy or stressful department
      correlated with lower engagement and higher burnout.

PMID- 27893518
TI  - Patient-Centered Medical Home Implementation and Burnout Among VA Primary Care
      Employees.
AB  - Burnout is widespread throughout primary care and is associated with negative
      consequences for providers and patients. The relationship between the patient
      centered medical home model and burnout remains unclear. Using survey data from
      8135 and 7510 VA primary care employees in 2012 and 2013, respectively, we
      assessed whether clinic-level medical home implementation was independently
      associated with burnout prevalence and estimated whether burnout changed among
      this workforce from 2012 to 2013. Adjusting for differences in respondent and
      clinic characteristics, we found that burnout was common among primary care
      employees, increased by 3.9% from 2012 to 2013, and was not associated with the
      extent of medical home implementation.

PMID- 27893519
TI  - Effects of Hospital Systems on Medical Home Transformation in Primary Care
      Residency Training Practices.
AB  - Most primary care residency training practices have close financial and
      administrative relationships with teaching hospitals and health systems. Many
      residency practices have begun integrating the core principles of the patient
      centered medical home (PCMH) into clinical workflows and educational experiences.
      Little is known about how the relationships with hospitals and health systems
      affect these transformation efforts. Data from the Colorado Residency PCMH
      Project were analyzed. Results show that teaching hospitals and health systems
      have significant opportunities to influence residency practices' transformation,
      particularly in the areas of supporting team-based care, value-based payment
      reforms, and health information technology.

PMID- 27893520
TI  - Impact of a Patient-Centered Medical Home Pilot on Utilization, Quality, and
      Costs and Variation in Medical Homeness.
AB  - This study evaluated the impact of a patient-centered medical home (PCMH) pilot
      on utilization, costs, and quality and assessed variation in PCMH components.
      Data included the New Hampshire Comprehensive Healthcare Information System and
      Medical Home Index (MHI) scores for 9 pilot sites. A quasi-experimental,
      difference-in-difference model with propensity score-matched comparison group was
      employed. MHI scores were collected in late 2011. There were no statistically
      significant findings for utilization, cost, or quality in the expected direction.
      MHI scores suggest variation in type and level of implemented features.
      Understanding site-specific PCMH components and targeted change enacted by PCMHs
      is critical for future evaluation.

PMID- 27893524
TI  - Visual Outcomes After SMILE, LASEK, and LASEK Combined With Corneal Collagen
      Cross-Linking for High Myopic Correction.
AB  - PURPOSE: To compare the visual and refractive outcomes of small-incision
      lenticule extraction (SMILE), laser-assisted subepithelial keratomileusis
      (LASEK), and LASEK combined with corneal collagen cross-linking (LASEK-CXL)
      surgery for high-degree myopia. METHODS: Medical records of patients with
      spherical equivalent (SE) greater than -6.00 diopters (D) treated with SMILE,
      LASEK, and LASEK-CXL were reviewed. Uncorrected distance visual acuity (UCVA),
      SE, and corneal haze were followed up in the 3 groups for 6 months. RESULTS: The
      SMILE group included 69 eyes, the LASEK group included 61 eyes, and the LASEK-CXL
      group included 40 eyes. At 6 months postoperatively, there were no statistically
      significant differences in UCVA between the SMILE, LASEK, and LASEK-CXL groups
      (logMAR 0.00 +/- 0.00, 0.01 +/- 0.08, and 0.01 +/- 0.08, respectively, P = 0.69).
      The averages of the absolute value of SE were 0.34 +/- 0.25 D, 0.50 +/- 0.36 D,
      and 0.42 +/- 0.34 D in the SMILE, LASEK, and LASEK-CXL groups, respectively (P =
      0.04). The percentages of the patients with a postoperative residual refractive
      error within +/-0.50 D were 84% in the SMILE group, 65% in the LASEK group, and
      76% in the LASEK-CXL group. The percentages of the patients with greater than
      20/25 postoperative UCVA were 100%, 91%, and 95%, respectively. SMILE produced no
      postoperative corneal haze. However, 18% of patients treated with LASEK and 25%
      of those treated with LASEK-CXL had corneal haze at 6 months postoperatively.
      CONCLUSIONS: SMILE, LASEK, and LASEK-CXL surgery appear to be safe and effective
      for high-degree myopic correction. However, the SMILE group had no haze and fewer
      induction of some higher-order aberrations compared with the LASEK and LASEK-CXL
      groups.

PMID- 27893526
TI  - Effect of oxygen therapy on myocardial salvage in ST elevation myocardial
      infarction: the randomized SOCCER trial.
AB  - OBJECTIVE: Recent studies suggest that administration of O2 in patients with
      acute myocardial infarction may have negative effects. With the use of cardiac
      MRI (CMR), we evaluated the effects of supplemental O2 in patients with ST
      elevation myocardial infarction (STEMI) accepted for acute percutaneous coronary
      intervention (PCI). MATERIALS AND METHODS: This study was a randomized-controlled
      trial conducted at two university hospitals in Sweden. Normoxic STEMI patients
      were randomized in the ambulance to either supplemental O2 (10 l/min) or room air
      until the conclusion of the PCI. CMR was performed 2-6 days after the inclusion.
      The primary endpoint was the myocardial salvage index assessed by CMR. The
      secondary endpoints included infarct size and myocardium at risk. RESULTS: At
      inclusion, the O2 (n=46) and air (n=49) patient groups had similar patient
      characteristics. There were no significant differences in myocardial salvage
      index [53.9+/-25.1 vs. 49.3+/-24.0%; 95% confidence interval (CI): -5.4 to 14.6],
      myocardium at risk (31.9+/-10.0% of the left ventricle in the O2 group vs. 30.0+/
      11.8% in the air group; 95% CI: -2.6 to 6.3), or infarct size (15.6+/-10.4% of
      the left ventricle vs. 16.0+/-11.0%; 95% CI: -4.7 to 4.1). CONCLUSION: In STEMI
      patients undergoing acute PCI, we found no effect of high-flow oxygen compared
      with room air on the size of ischemia before PCI, myocardial salvage, or the
      resulting infarct size. These results support the safety of withholding
      supplemental oxygen in normoxic STEMI patients.

PMID- 27893525
TI  - Outcomes of Descemet Membrane Endothelial Keratoplasty in Patients With Previous
      Glaucoma Surgery.
AB  - PURPOSE: To evaluate outcomes of Descemet membrane endothelial keratoplasty
      (DMEK) in eyes with previous trabeculectomy or a drainage device. METHODS: This
      is a retrospective study of 108 consecutive DMEK performed between October 2013
      and December 2015. All eyes were divided into 3 groups: surgical treatment (ST)
      group, medical treatment (MT) group, and control group. Visual improvement,
      endothelial cell loss, and postoperative complications, including rejection,
      graft failure, and intraocular pressure elevation (>=25 mm Hg) were evaluated.
      RESULTS: The length of follow-up was 9.7 +/- 7.3 months. Best-corrected visual
      acuity (BCVA) improved postoperatively in 85.3% of the ST group, 100% of the MT
      group, and 93% of the control (P = 0.24). Significantly more lines of BCVA were
      gained in the ST and MT groups (8.1 +/- 8.1 and 9.2 +/- 6.3 lines, respectively)
      than in the control (4.8 +/- 5.6 lines, P < 0.05). The mean time to BCVA was 2.9
      +/- 2.8 months for the ST group, 4.7 +/- 5.3 months for the MT group, and 3.0 +/-
      3.3 months for the control (P = 0.75). Endothelial cell loss was greater in the
      ST group (44.6 +/- 17.8%) than in the MT group (29.9 +/- 12.0%) and the control
      group (32.7 +/- 11.3%, P = 0.001). There was one primary failure and no secondary
      graft failures. The overall rejection rate was 0.9%. Postoperative intraocular
      pressure elevation was less common in the ST group (14.7%) and control (23.3%)
      than in the MT group (50.0%, P = 0.04). There was no difference in the air
      injection rate among all groups (P = 1.0). CONCLUSIONS: DMEK in eyes with
      previous trabeculectomy and drainage device can result in very good short-term
      outcomes.

PMID- 27893527
TI  - Editorial.

PMID- 27893529
TI  - The Role of Theory-Specific Techniques and Therapeutic Alliance in Promoting
      Positive Outcomes: Integrative Psychotherapy for World Trade Center Responders.
AB  - World Trade Center responders demonstrate high symptom burden, underscoring the
      importance of refining treatment approaches for this cohort. One method is
      examining the impact of therapy techniques on outcomes, and the interactions
      between technique and alliance on outcomes. This study a) examined the
      interaction of early treatment techniques on integrative psychotherapy outcomes
      and b) explored whether associations differed at varying levels of alliance.
      Twenty-nine adult responders diagnosed with partial or full posttraumatic stress
      disorder received outpatient psychotherapy and completed weekly measures of
      alliance, technique, and symptom distress. Analyses indicated significant
      interactions between 1) alliance and psychodynamic interventions on outcomes and
      2) alliance and cognitive behavioral (CB) interventions on outcomes. Clients with
      high alliance had better outcomes when their therapist used fewer CB techniques.
      No meaningful differences were found between technique and outcomes for clients
      with lower alliance. These findings reiterate the critical roles technique and
      responsiveness to the alliance play in engendering successful outcomes.

PMID- 27893528
TI  - Management of Older Inpatients Who Refuse Nonpsychiatric Medication Within
      Birmingham and Solihull Mental Health NHS Foundation Trust: Audit.
AB  - The effects of poor medication compliance are well documented and include
      increased morbidity, early mortality, and financial costs to the society.
      According to national guidelines, when a competent patient refuses medication,
      the doctor on duty has a responsibility to ensure the patient understands their
      proposed course of action. The aims of this audit were to evaluate whether this
      consultation was taking place within older in-patient units across Birmingham and
      Solihull Mental Health NHS Foundation Trust when patients refuse nonpsychiatric
      medicines. Poor compliance was defined as more than five refusals of a
      nonpsychiatric medication over a 4-week period. A discussion with the duty doctor
      occurred in 75% of cases (27/36), which resulted in a change in prescription or
      compliance in 59% (16/27 patients). After patient refusal of medication, a
      consultation with the duty doctor is likely to improve compliance and uncover
      salient issues particularly in regards to capacity and drug suitability.

PMID- 27893533
TI  - Half the Truth is Often a Great Lie: Over a Hundred Years of Controversy on
      Pancreatic Fistula Between Pancreaticogastrostomy and Pancreaticojejunostomy
      After Pancreaticoduodenectomy.

PMID- 27893532
TI  - The Effect of Hospital Volume on Breast Cancer Mortality.
AB  - OBJECTIVE: The aim of this study was to determine whether hospital volume was
      associated with mortality in breast cancer, and what thresholds of case volume
      impacted survival. BACKGROUND: Prior literature has demonstrated improved
      survival with treatment at high volume centers among less common cancers
      requiring technically complex surgery. METHODS: All adults (18 to 90 years) with
      stages 0-III unilateral breast cancer diagnosed from 2004 to 2012 were identified
      from the American College of Surgeons National Cancer Data Base (NCDB). A
      multivariable Cox proportional hazards model with restricted cubic splines was
      used to examine the association of annual hospital volume and overall survival,
      after adjusting for measured covariates. Intergroup comparisons of patient and
      treatment characteristics were conducted with X and analysis of variance (ANOVA).
      The log-rank test was used to test survival differences between groups. A
      multivariable Cox proportional hazards model was used to estimate hazard ratios
      (HRs) associated with each volume group. RESULTS: One million sixty-four thousand
      two hundred and fifty-one patients met inclusion criteria. The median age of the
      sample was 60 (interquartile range 50 to 70). Hospitals were categorized into 3
      groups using restricted cubic spline analysis: low-volume (<148 cases/year),
      moderate-volume (148 to 298 cases/year), and high-volume (>298 cases/year).
      Treatment at high volume centers was associated with an 11% reduction in overall
      mortality for all patients (HR 0.89); those with stage 0-I, ER+/PR+ or ER+/PR-
      breast cancers derived the greatest benefit. CONCLUSIONS: Treatment at high
      volume centers is associated with improved survival for breast cancer patients
      regardless of stage. High case volume could serve as a proxy for the
      institutional infrastructure required to deliver complex multidisciplinary breast
      cancer treatment.

PMID- 27893534
TI  - Clinical Predictors of Positive Postoperative Blood Cultures.
AB  - OBJECTIVE: To define clinical features of surgical patients in whom postoperative
      blood cultures are likely to identify pathogens. BACKGROUND: Bacteremia is a
      worrisome postoperative complication and blood cultures (BCx) are routinely used
      for evaluation of postoperative bacteremia, but are costly and not always
      diagnostic. Better methods are needed to select patients in whom BCx identify
      pathogens. METHODS: We reviewed records of patients >=18 years old with BCx drawn
      <=10 days after surgery in 2013 seeking independent predictors of positive
      cultures by simple and multiple logistic regression models with statistical
      significance at alpha = 0.05. RESULTS: Of 1804 BCx, excluding contaminants
      yielded 1780 cultures among 746 patients for analysis. The yield was low, with
      only 4% identifying potential pathogens. Positive BCx were most common after
      cardiac, ear/nose/throat, obstetric, and urologic procedures [odds ratio (OR)
      =10.3, P < 0.001 vs low-yield procedures: eg, gynecologic, neurosurgical, plastic
      surgical, podiatric, transplant]. Cultures more often grew pathogens when drawn
      in association with higher peak temperature (Tmax, P = 0.001) and longer interval
      from procedure to Tmax (P = 0.001). Antibiotic therapy at time of culture reduced
      yield (2.9% with vs 5.5% without antibiotics, P = 0.007). Multivariable logistic
      regression analysis found antibiotics at culture, procedure specialty, Tmax, and
      postoperative timing of Tmax were associated with blood culture results.
      CONCLUSIONS: Ordering blood cultures based on fever or another single predictor
      inconsistently identifies pathogens. Our dataset, the largest available, identify
      clinical predictors in the first 10 postoperative days to guide identification of
      patients with bacteremia.

PMID- 27893536
TI  - Repair of a Composite Cheek and Nose Defect.

PMID- 27893535
TI  - Cytoplasmic HuR Status Predicts Disease-free Survival in Resected Pancreatic
      Cancer: A Post-hoc Analysis From the International Phase III ESPAC-3 Clinical
      Trial.
AB  - OBJECTIVES: We tested cytoplasmic HuR (cHuR) as a predictive marker for response
      to chemotherapy by examining tumor samples from the international European Study
      Group of Pancreatic Cancer-3 trial, in which patients with resected pancreatic
      ductal adenocarcinoma (PDA) received either gemcitabine (GEM) or 5-fluorouracil
      (5-FU) adjuvant monotherapy. BACKGROUND: Previous studies have implicated the
      mRNA-binding protein, HuR (ELAVL1), as a predictive marker for PDA treatment
      response in the adjuvant setting. These studies were, however, based on small
      cohorts of patients outside of a clinical trial, or a clinical trial in which
      patients received multimodality therapy with concomitant radiation. METHODS:
      Tissue samples from 379 patients with PDA enrolled in the European Study Group of
      Pancreatic Cancer-3 trial were immunolabeled with an anti-HuR antibody and scored
      for cHuR expression. Patients were dichotomized into groups of high versus low
      cHuR expression. RESULTS: There was no association between cHuR expression and
      prognosis in the overall cohort [disease-free survival (DFS), P = 0.44; overall
      survival, P = 0.41). Median DFS for patients with high cHuR was significantly
      greater for patients treated with 5-FU compared to GEM [20.1 months, confidence
      interval (CI): 8.3-36.4 vs 10.9 months, CI: 7.5-14.2; P = 0.04]. Median DFS was
      similar between the treatment arms in patients with low cHuR (5-FU, 12.8 months,
      CI: 10.6-14.6 vs GEM, 12.9 months, CI: 11.2-15.4). CONCLUSIONS: Patients with
      high cHuR-expressing tumors may benefit from 5-FU-based adjuvant therapy as
      compared to GEM, whereas those patients with low cHuR appear to have no survival
      advantage with GEM compared with 5-FU. Further studies are needed to validate HuR
      as a biomarker in both future monotherapy and multiagent regimens.

PMID- 27893537
TI  - A Novel Method of Processing Single Sections Too Large to Fit on One Glass Slide
      in Mohs Micrographic Surgery.

PMID- 27893538
TI  - Blood Aspiration Test for Cosmetic Fillers to Prevent Accidental Intravascular
      Injection in the Face.

PMID- 27893539
TI  - Comparative Efficacy of Radiofrequency and Pulsed Dye Laser in the Treatment of
      Rosacea.
AB  - BACKGROUND: Laser and light-based therapies have been used successfully in the
      treatment of rosacea; however, evidence is lacking regarding the efficacy of
      radiofrequency (RF). OBJECTIVE: This study evaluated the efficacy of RF in the
      treatment of rosacea compared with pulsed dye laser (PDL). METHODS: Thirty
      patients with rosacea (erythematotelangiectatic rosacea [ETR], n = 20;
      papulopustular rosacea [PPR], n = 10) were enrolled in a randomized, controlled,
      split-face study. The patients were treated with RF on one side and PDL on the
      other side. Each treatment consisted of 3 sessions at 4-week intervals and
      followed up until 4 weeks after the last treatment. Efficacy was assessed by
      rosacea severity score, erythema index, lesion counts, physician's subjective
      evaluation, and patient's satisfaction. RESULTS: Radiofrequency and PDL resulted
      in significant improvement in severity scores and erythema and 70% of the
      patients receiving RF treatment showed a clinical improvement of >50%. No
      significant difference was noted between RF and PDL treatment in ETR. However, RF
      treatment led to a significantly greater decrease in papulopustular lesion count
      and rosacea severity score in PPR compared with PDL treatment. CONCLUSION: RF
      therapy was effective in the treatment of rosacea. It should be considered an
      alternative therapeutic option, especially in PPR.

PMID- 27893540
TI  - Eight Years' Experience of Sentinel Lymph Node Biopsy in Melanoma Using
      Lymphoscintigraphy and Gamma Probe Detection After Radiocolloid Mapping.
AB  - BACKGROUND: Isosulfan blue dye peripheral injection is used in preoperative
      sentinel lymph node (SLN) identification alone or, to increase sensitivity, in
      conjunction with radiocolloid mapping. However, isosulfan blue dye has certain
      drawbacks and limitations. OBJECTIVE: This study assesses the authors' experience
      of SLN biopsy using only radiocolloid tracer. MATERIALS AND METHODS: Between 2000
      and 2008, 218 patients underwent SLN biopsy with radiocolloid mapping,
      preoperative localization by lymphoscintigraphy and intraoperative confirmation
      by gamma probe in primary malignant cutaneous melanoma. RESULTS: Mean Breslow
      index was 2.1 mm. The SLN biopsy success rate was above 98% at all sites and 87%
      in head and neck locations. The 5-year overall survival rate was 90% and that of
      5-year disease-free survival was 80%. False-negative rate, with a mean follow-up
      time of 41 months, was 5.5%. CONCLUSION: Sentinel lymph node biopsy can be
      successfully performed in patients with melanoma using only radiocolloid tracer
      without blue dye staining. In circumstances where blue dye cannot be used such as
      head and neck tumors, allergic reactions and pregnancy, radiocolloid tracer
      mapping alone is not a loss of chance for patients with melanoma.

PMID- 27893541
TI  - Treatment of Palmar Hyperhidrosis With Needle Injection Versus Low-Pressure
      Needle-Free Jet Injection of OnabotulinumtoxinA: An Open-Label Prospective Study.
AB  - BACKGROUND: OnabotulinumtoxinA (OnabotA) injections are effective to treat palmar
      hyperhidrosis (HH) but are quite painful. OBJECTIVE: To evaluate efficacy and
      pain of OnabotA injection using a needle-free jet apparatus compared with the
      traditional needle injection to treat palmar HH. METHODS: Twenty patients were
      recruited for a prospective open-label study. Their right hand was injected with
      1% lidocaine with a jet injector, after which OnabotA was injected with a needle.
      The left hand was injected with OnabotA directly using the jet injector. Pain
      scores were recorded for both techniques. At 0, 1, 3, and 6 months, severity of
      palmar HH was evaluated with the Hyperhidrosis Disease Severity Scale (HDSS).
      RESULTS: One point reduction in the HDSS score at 1 month showed no statistical
      difference between both hands (p = .451). However, the HDSS score at 1 month from
      baseline dropped by 1.6 for the hand treated with traditional needle injection of
      OnabotA compared with 1.25 for the hand treated with jet injections (p = .031).
      There was no statistical difference in the pain on injection with both techniques
      (p = .1925). CONCLUSION: This study demonstrates effective and relatively
      painless use of a low-pressure jet injector for OnabotA in palmar HH.

PMID- 27893542
TI  - Safety and Suitability of Finger Replantations as a Residency Training Procedure:
      A Retrospective Cohort Study With Analysis of the Initial Postoperative Outcomes.
AB  - Finger replantations demand technical excellence in microsurgery and hand trauma
      care. The objective of this study was to determine whether finger replantations
      constitute an appropriate and safe procedure for residency training.
      Additionally, the prognostic risk factors for the need to take a replanted finger
      back to the operation room and replant failure were analyzed.All patients who
      underwent finger replantation after complete amputation between 2007 and 2015
      were included in a retrospective comparative study. These patients were either
      treated by an attending plastic surgeon (cohort 1) or by a postgraduate year 5 or
      6 resident under supervision (cohort 2). Logistic regression analysis was used to
      identify the prognostic risk factors for emergent take backs and replant
      failures.A total of 109 completely amputated fingers were replanted in 89
      patients. Fifty-seven digits were replanted in cohort 1, and 52 digits were
      replanted in cohort 2. Patient demographic data revealed an equal distribution
      between the two cohorts with an overall finger-replantation success rate of
      67.0%. The prognostic risk factors related to increased take back and replant
      failure rates were fewer than two venous anastomoses (take back odds ratio [AOR],
      0.27; confidence interval (CI), 0.12-0.63; and replant failure AOR, 0.21; 95% CI,
      0.08-0.55) and intraoperative noticeable problems regarding the vascular
      anastomoses (take back AOR, 2.26; 95% CI, 0.96-5.33 and replant failure AOR,
      2.45; 95% CI, 1.00-6.00). The type of surgeon did not exhibit an influence on the
      risk of take back (OR, 1.14; 95% CI, 0.53-2.41) or replant failure (OR, 1.03; 95%
      CI, 0.46-2.30). Similarly, after adjusting for all risk factors, the risks for
      take backs (AOR, 1.04; 95% CI, 0.46-2.36) and replant failures (AOR, 0.91; 95%
      CI, 0.38-2.19) did not differ between the 2 cohorts.Finger replantations can be
      applied as a safe procedure in residency training under standardized conditions
      and do not negatively affect quality of care. Technical proficiency in
      microsurgery and elective and trauma hand care as well as supervision by an
      experienced plastic or hand surgeon are mandatory. Regardless of the surgeons'
      experience, fewer than 2 venous anastomoses and the presence of intraoperative
      vascular anomalies represent significant prognostic risk factors for
      postoperative complications.

PMID- 27893543
TI  - Changes in Intestinal Microbiota Following Combination Therapy with Fecal
      Microbial Transplantation and Antibiotics for Ulcerative Colitis.
AB  - BACKGROUND: Fecal microbiota transplantation (FMT) is a potential therapeutic
      approach to restore normal intestinal microbiota in patients with ulcerative
      colitis (UC), which is associated with dysbiosis; however, treatment efficacy
      remains unclear. Hence, we studied the impact of antibiotic pretreatment with
      amoxicillin, fosfomycin, and metronidazole (AFM therapy) and FMT versus AFM
      alone. METHODS: AFM therapy was administered to patients for 2 weeks until 2 days
      before FMT. Patients' spouses or relatives were selected as donor candidates.
      Donor fecal samples were collected on the day of administration and transferred
      into the patient's colon by colonoscopy within 6 hours. Microbiome analysis was
      performed by 16S rRNA next-generation sequencing. RESULTS: Patients with mild-to
      severe active UC (combination-therapy group, n = 21; AFM monotherapy group, n =
      20) were included. Thirty-six patients completed this assessment (combination
      therapy group, n = 17; AFM monotherapy group, n = 19). A higher clinical response
      was observed after combination therapy compared with AFM monotherapy at 4 weeks
      after treatment. After the 2-week AFM therapy, the Bacteroidetes composition was
      nearly abolished. The Bacteroidetes proportion recovered in clinical responders
      at 4 weeks after FMT was not observed in the AFM monotherapy group. Persistent
      antimicrobial-associated dysbiosis found in the AFM monotherapy group was
      reversed by FMT. The recovery rate of Bacteroidetes at 4 weeks after FMT
      correlated with endoscopic severity. CONCLUSIONS: FMT following antimicrobial
      bowel cleansing synergistically contributes to the recovery of the Bacteroidetes
      composition, which is associated with clinical response and UC severity. Thus,
      this therapeutic protocol may be useful for managing UC.

PMID- 27893545
TI  - Effects of Preoperative Methotrexate on Complications After Surgery for
      Inflammatory Bowel Disease.

PMID- 27893544
TI  - Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among
      Individuals with Crohn's Disease.
AB  - INTRODUCTION: Adipose tissue in mesenteric fat plays a key role in systemic and
      luminal inflammation. However, little is known about the role of visceral adipose
      tissue (VAT) and its interaction with genetic predisposition in Crohn's disease
      (CD) progression. METHODS: Our study population included patients with CD
      enrolled in Prospective Registry in Inflammatory Bowel Disease Study at
      Massachusetts General Hospital (PRISM). VAT volume was measured from computed
      tomography using Aquarius 3D. We used logistic regression models to estimate the
      multivariable-adjusted odds ratio and 95% CI. We tested for effect modification
      by genetic predisposition using the log likelihood ratio test. RESULTS: Among 482
      patients with CD with available data on VAT, 174 developed penetrating disease,
      132 developed stricturing disease, 147 developed perianal disease, and 252
      required surgery. Compared with individuals in the lowest quartile of VAT volume,
      the multivariable-adjusted odds ratio of surgery among individuals in the highest
      quartile was 2.02 (95% CI, 1.09-3.76; Ptrend = 0.006). Similarly, the risk of
      penetrating disease seemed to increase with greater VAT volume (Ptrend = 0.022)
      but not stricturing or perianal disease (all Ptrend > 0.23). The associations
      between VAT volume and CD complications were not modified by genetic
      predisposition (all Pinteraction > 0.12). CONCLUSIONS: Visceral adiposity as
      measured by VAT volume may be associated with a significant increase in the risk
      of penetrating disease and surgery in CD. Our data suggest that visceral
      adiposity as measured by VAT may negatively impact long-term progression of CD
      regardless of genetic predisposition.

PMID- 27893546
TI  - Cutaneous Vasculitis in a Patient with Crohn's Disease Treated with Adalimumab.

PMID- 27893548
TI  - Pressureless Orbital Decompression for Myopic Proptosis.
AB  - Orbital decompression surgery increases the orbital volume. It has rarely been
      used for proptosis of the large highly myopic globe. However, external
      decompression surgery carries significant risks because of the large thin-walled
      globe. The authors report the first use of endoscopic medial wall orbital
      decompression surgery in this setting to obviate the risk of globe
      pressure.Endoscopic medial wall decompression brought about a 4 mm reduction of
      proptosis, correction of exotropia and elimination of retrobulbar ache providing
      good symmetry with the fellow eye.Endoscopic medial wall orbital decompression
      can be very effective for correcting the proptosis of high myopia and minimizes
      the risk of damage to the very large, thin-walled globe.

PMID- 27893549
TI  - How Deleterious Is Facial Nerve Dissection for the Facial Nerve in Parotid
      Surgery: An Electrophysiological Evaluation.
AB  - OBJECTIVE: This study was conducted to investigate subclinical
      electrophysiological deleterious effect due to microtrauma to the nerve in
      response to the dissection of a tumor and parotid tissue from the facial nerve
      and its branches and surgical traction experienced during the operation. METHODS:
      The study included 34 adult patients who underwent parotidectomy operations under
      intraoperative facial nerve monitoring. Three measurements were taken from each
      patient to evaluate facial nerve functions, with 3 stimuli of different
      intensities applied with different timing. An initial stimulus of 1 mA was
      applied to confirm the identification of the main trunk of the facial nerve
      (Group 1: Initial-Normal). Then, a threshold value was found by stimulating the
      main trunk until muscle fasciculations were observed on facial muscles (Group 2:
      Basal-Minimal). The same procedure was repeated after the tumor was resected
      (Group 3: Final-Minimal). RESULTS: There was no significant difference between
      the stimulus thresholds of Group 2 (0.31 mA) and Group 3 (0.30 mA). The highest
      amplitude in all 3 groups was observed at the mental branch, and the lowest at
      the frontal. The highest latency value was measured at the frontal branch and the
      lowest at the mental branch. Five (14.7%) of the patients developed postoperative
      pareses that was completely resolved by the seventh postoperative day visit in
      these patients. CONCLUSION: This study demonstrated that the surgical trauma of a
      meticulously conducted dissection and surgical traction did not cause any
      deleterious electrophysiological alteration on the facial nerve.

PMID- 27893550
TI  - Application of Dexamethasone in the Masseter Muscle During the Surgical Removal
      of Lower Third Molars.
AB  - PURPOSE: The aim of the present study was to analyze the effect of the
      application of dexamethasone in the masseter muscle during third molar surgery.
      METHODS: This randomized, clinical trial used dependent samples and the split
      mouth method. A sample of 30 patients, with impacted or semi-impacted third
      molars, as well as vertical and mesioangular positions of a similar surgical
      difficulty (on both sides), was subjected to 2 operations: an experimental
      operation and a control procedure, with a 30-day wash-out. The choice of which
      group would be experimental or control was random. The experimental group
      received 8 mg of dexamethasone, which was applied directly to the masseter muscle
      immediately after surgery. The control group did not receive corticosteroids.
      Seven and 15 days after the surgery, the patients were assessed in relation to
      their levels of pain, trismus, and edema. RESULTS: Concerning edema and trismus,
      there was a significant difference (P <0.05) between the control and experimental
      groups. As for the pain scale, no significant differences were found between the
      presence or absence of corticoids. CONCLUSION: The present study concluded that
      the application of dexamethasone in the masseter muscle effectively reduces edema
      and trismus, but does not affect pain.

PMID- 27893551
TI  - Mid-Face Degloving: An Alternate Approach to Extended Osteotomies of the Midface.
AB  - Extended osteotomies for mid-face advancement require generous exposure of the
      anterior maxilla, nasal bones, infraorbital rims, orbital floor, zygoma, and the
      anterior third of the zygomatic arches. This cannot be obtained with an exclusive
      transoral approach. Hence, the surgeon is usually compelled to utilize
      supplemental cutaneous incisions that are a compromise on the purpose behind a
      cosmetic surgery. In order to alleviate the need for such compromise, the authors
      advocate the mid face degloving approach for extended osteotomies at Lefort II
      and Lefort III levels. Mid face degloving involves a combination of
      circumvestibular incision, with inter cartilaginous and transfixation components
      from a nasal incision. The authors have utilized this technique for 9 patients
      and documented favorable results. The purpose of this paper is to focus the
      utility of this approach in orthognathic surgery and promote this as a viable
      alternative to traditional approaches in surgery of the mid face because of the
      absence of external scars.

PMID- 27893552
TI  - Surgically Clipping a Posterolaterally Projecting Posterior Communicating Artery
      Aneurysm With Anterior Petroclinoid Fold Fenestration.
AB  - The anterior petroclinoid fold (APF) is a ligamentous structure consisting of
      collagen fiber and extends from the petrous apex to the anterior clinoid process.
      During the surgical clipping of some posterolaterally projecting posterior
      communicating artery aneurysms, it may pose a technical challenge due to
      obscuration of the aneurismal neck by the APF. Herein, the authors describe a
      simple and effective technique utilizing fenestration of the APF to facilitate
      visualization and surgical clipping of these aneurysms. To the best knowledge of
      us, this technique of the APF fenestration has been reported in only a few
      patients.

PMID- 27893553
TI  - Healing Effects of Platelet-Rich Plasma on Peripheral Nerve Injuries.
AB  - Regeneration of peripheral nerve injuries (PNIs) has been a major challenging
      issue in regenerative medicine and tissue engineering. Inferior alveolar nerve
      and lingual nerve injuries are the major difficulties and complications of oral
      surgeries following dental implant placement, etc. The aim of this study was to
      systematically review the effects of platelet-rich plasma (PRP) on the
      regeneration of PNIs. Medline NCBI databases were searched for related articles
      up to and including May 2016. Being published in English papers, use of PRP in
      peripheral nerve regeneration, in vivo studies, and having histological
      evaluations was the inclusion criteria. Seventeen papers were selected according
      to the inclusion and exclusion criteria, and categorized regarding PNIs types
      including cut or crushed injuries. The effects of using PRP only or in
      combination with cells on the functional recovery and histological assessments
      are discussed and compared with the other treatments such as autologous nerve
      graft, acellular nerve allograft, and synthetic nerve conduits. The authors also
      clarified the perspectives in the current field. Consequently, PRP demonstrated
      positive effects on healing of the nerve function as well histological
      improvements in cut nerve PNIs model; however, more studies in the field of
      crushed nerves are needed to arrive at an evidence-based conclusion.

PMID- 27893554
TI  - Stapler Esophageal Closure During Total Laryngectomy.
AB  - Mechanical esophageal closure with stapler during total laryngectomy has been
      used by various authors to decrease the surgical time and pharyngocutaneous
      fistula (PCF) rates. In a few of the studies, surgical site infection (SSI) rates
      are mentioned and none of the studies emphasize the effect of decreased surgical
      time on postoperative cardiovascular and cerebrovascular complications. In this
      study, the authors compared the PCF rates, SSI rates, operation times between 30
      mechanical stapler and 40 manual esophageal closure during total laryngectomy for
      laryngeal cancer patients. National Nasocomial Infections Surveillance system
      (NNISS) scores were recorded and compared between groups. Total laryngectomy and
      total operation times were lower in the stapler group patients (P < 0.001 for
      total laryngectomy time, P = 0.024 for total operation time). There were lower
      rates of pharyngocutaneous fistula (P = 0.032), surgical site infection (P =
      0.019), and NNISS scores (P = 0.009) in the stapler group. There was no
      statistically significant difference between groups regarding postoperative
      systemic complications (P = 0.451). In conclusion, stapler esophageal closure
      decreases operation time, PCF, SSI rates, and NNISS scores but not the systemic
      complication rates. Comorbid illnesses and prolonged surgical time are risk
      factors for postoperative systemic complications in total laryngectomy patients,
      but patients with additional illnesses must not encourage the surgeon to use
      stapler for decreasing postoperative systemic complications.

PMID- 27893555
TI  - Changes at Mean Platelet Volume and Platelet Distribution Width Levels After
      Septoplasty and Its Correlation With Epworth Sleepness Scale.
AB  - OBJECTIVE: Nasal septum deviation may affect cardiopulmonary system. Those
      effects can be determined via blood tests and Epworth sleepness scale (ESS). In
      this study, it was aimed to measure mean platelet volume (MPV) and platelet
      distribution width (PDW) in patients with nasal septum deviation and to assess
      changes at their levels after septoplasty. Furthermore, it was purposed to
      document the correlation between ESS score and MPV, PDW levels. METHODS: Eighty
      one patients who underwent septoplasty and 50 healthy controls composed the study
      group. Epworth sleepness scale was performed to all patients preoperatively and
      patients were divided into 2 groups in terms of ESS scores. Mean platelet volume
      and PDW levels were measured preoperatively and it was repeated postoperatively.
      RESULTS: In Group A (ESS <10), MPV reduced from 8.48 +/- 0.38 fl to 8.47 +/- 0.36
      fl (P >0.05), PDW reduced from 14.56 +/- 1.27% to 14.43 +/- 1.03% after surgery
      (P >0.05). On the other hand, in Group B (ESS >=10), MPV reduced from 9.54 +/-
      0.68 fl to 8.87 +/- 0.44 fl (P <0.001), PDW reduced from 17.15 +/- 1.75% to 15.35
      +/- 1.29% postoperatively (P <0.001). CONCLUSIONS: Statistically significant
      improvements at MPV and PDW levels after surgery were noticed only at patients
      with excessive daytime sleepness whose ESS score was 10 or above. According to
      this, it would be preferable to operate these patients earlier to protect them
      from systemic effects.

PMID- 27893556
TI  - Ferromagnetic Artifacts Seen Incidentally on Magnetic Resonance Imaging After
      Temporomandibular Joint Surgery.

PMID- 27893557
TI  - Changes in Upper Airway Volume Following Orthognathic Surgery.
AB  - Reduced volume of the internal skeletal dimensions of the face is 1 of the main
      causes of obstructive sleep apnea, and attention to patients' airways is
      necessary when planning orthognathic treatment. This study aims to describe
      changes in upper airway volume following virtually planned orthognathic surgery.A
      retrospective pilot study was designed with 30 randomly selected patients (10 men
      and 20 women, aged 23.1 +/- 6.8 years, molar-relations: 15 neutral, 8 distal, and
      7 mesial). Cone-beam computed tomography scans were performed before surgery and
      1 week following surgery. The authors did total upper airway volume measurements
      and obtained 1-mm slices at vertical levels in the velo-, oro-, and hypopharynx
      and at the smallest visible cross-section.Measurements before and after surgery
      were compared using Student t test.After orthognathic surgery, the minimum cross
      sectional area at the vertical level increased from 83 mm +/- 33 before surgery
      to 102 mm +/- 36 after surgery (P = 0.019). In patients with neutral and distal
      occlusions, the minimum cross-sectional slice volume increased in 87% but in only
      57% with mesial occlusion.The present findings suggest that orthognathic surgery
      increases upper airway volume parameters, but a few patients have continued
      impairment of the airways following orthognathic surgery. Further studies are
      needed to confirm an individual surgical planning approach that potentially could
      bring the minimum cross sectional area out of the risk zone.

PMID- 27893558
TI  - Medial Femoral Condyle Free Flap for Premaxillary Reconstruction in Median Facial
      Dysplasia.
AB  - OBJECTIVE: Median facial dysplasia is a distinct development anomaly of the
      craniofacial region that is characterized by deficient mid facial structures.
      Medial femoral condyle free flap could be used as a bony flap, and the unique
      characteristics of this flap provide the surgeons with the periosteal component
      as well. In this work, the authors present our experience with a patient of
      median facial dysplasia with unilateral cleft lip, cleft palate, and premaxillary
      deficiency. METHODS: The patient was diagnosed with median facial dysplasia
      accompanied by unilateral cleft lip, cleft palate, and premaxillary. She had
      presented with severe midface hypoplasia with missing premaxillary bone.
      Premaxillary reconstruction was performed with the use of medial femoral condyle
      free flap. RESULTS: Medial femoral condyle free flap was successfully used for
      premaxillary reconstruction. The flap fitted well to the alveolar bony gap. Since
      the flap is a periosteal bone flap, the gingival mucosa was reconstructed very
      well. The lip harmony was considerably restored compared with the preoperative
      status. CONCLUSIONS: Although several other options are available, the medial
      femoral condyle free flap is particularly suited for the reconstruction of median
      facial dysplasia.

PMID- 27893560
TI  - Cranial Bone Graft Donor Site Reconstruction.
AB  - My most important concern, in my entire experience with cranial bone grafting
      procedures, is managing the bone graft donor site such as donor site cavity from
      harvesting and weakness of the cranium. The most common patient complaint,
      following cranial bone grafting for aesthetic indications, is the presence of a
      cavity at the donor site. The authors have managed more than 200 patients since
      2001, wherein the cranial bone graft-donor sites were reconstructed with tiny
      bone chip lamellae harvested from the area adjacent to the donor site. This
      procedure was associated with a low incidence of patient complaints, thereby
      suggesting higher patient satisfaction. This approach for cranial bone grafting
      appears to have a high patient acceptance.

PMID- 27893559
TI  - Personalized Reconstruction of Traumatic Orbital Defects Based on Precise Three
      Dimensional Orientation and Measurements of the Globe.
AB  - OBJECTIVE: The aim of the study was to precisely assess the severity of traumatic
      orbital defects and techniques for personalized orbital reconstruction. METHODS:
      A retrospective study was conducted in 97 patients with traumatic orbital defects
      who were treated in our hospital between July 2003 and June 2012. Pre- and
      postoperative spiral computed tomography scans were performed in all patients. A
      spatial orientation technique was used to measure the three-dimensional position
      of the globe and calculate the changes in the orbital volume. Subsequently, a
      computer-assisted technique and a rapid prototyping technique were used to create
      a personalized orbital model to aid in the planning of surgery as well as the
      preforming of implants and bone plates. During surgery, the herniated orbital
      contents were returned; the preformed titanium mesh, Medpor, or other implants
      were placed; the orbital shape in the defect site was precisely restored; and
      normal proportions between the orbital walls and orbital contents were regained.
      The treatment outcomes were evaluated with respect to postoperative appearance,
      patients' satisfaction, ophthalmologic examination, and computed tomography scan.
      The complications were analyzed accordingly. RESULTS: Satisfactory results were
      achieved in all patients with the following exceptions: 1 patient with an
      unsatisfactory facial appearance; 2 patients with old trauma and an unfavorable
      correction of enophthalmos who experienced diplopia with no significant
      improvement within 6 months after surgery; and 2 patients of mild postoperative
      lower eyelid ectropion. All other patients achieved satisfactory treatment
      effects, that is, the orbital shape in the defect site was precisely restored,
      and normal proportions between the orbital walls and orbital contents were
      regained. There were no other severe complications reported. CONCLUSIONS: In
      patients with traumatic orbital defects, accurate digital evaluations of the
      three-dimensional position of the globe and changes in the orbital volume aid in
      surgical planning with a personalized model and promote early surgery with
      minimal trauma. When the orbital volume was restored and the position of the
      globe was maintained or corrected, the precise reconstruction of the anatomic
      shape of the orbit was concurrently completed. Personalized orbital
      reconstruction can improve the efficacy of plastic surgery in patients with
      orbital deformities.

PMID- 27893561
TI  - Finite Element Evaluation of Different Osteosynthesis Variations That Used After
      Segmental Mandibular Resection.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of different
      reconstruction plates and screw combinations on stress distribution of segmental
      resected mandibles using finite element analysis. METHODS: Lateral (L) and
      lateral-central (LC) defects were simulated by a computer aided design modeling.
      The straight (s) and angular (a) titanium locking reconstruction plates of 2.5 mm
      (12 holes for L defects and 16 holes for LC defects) were modeled. Each screw was
      2.5 mm in diameter and 10 mm in length. A total of 20 different screw placement
      combinations were created. The bite force used in the present model was a
      unilateral molar clench. The data obtained from finite element analysis were
      recorded as von Mises, maximum principle and minimum principle stress values.
      RESULTS: It was observed that stress values on neck of screw were higher for
      screws close to the resection area. When the first screw was loosened, the stress
      on the plate body and the remaining screws increased. Principle stress values
      were within the tolerance limits of the bone. CONCLUSION: The highest stress is
      observed in the screws nearest to the resection edge. Therefore, it is very
      important to place a screw adjacent to the resection edge.

PMID- 27893562
TI  - Clinical Evaluation of Zygomatic Implant-Supported Fixed and Removable
      Prosthesis.
AB  - The aim of our study was to present success and complication rates of 32
      zygomatic implants (ZI) and compare satisfaction of patients rehabilitated with
      ZI supported hybrid prosthesis in atrophic jaws and removable prosthesis in
      maxillary defects. Sixteen patients who have been diagnosed as atrophic maxilla
      or maxillary defect were treated with ZI supported hybrid or removable prosthesis
      between 2008 and 2016 years, respectively. Thirty-two of 70 implants were placed
      in the zygomatic bone. Two prosthetic groups were compared 1 month after
      prosthesis delivery in terms of general satisfaction, stability, performance,
      esthetics, phonetics, hygiene level based on visual analog scale. Zygomatic
      implants success rate was found 93.7% after a mean follow-up of 28 +/- 22 months
      (range 6-96 months). Thirty of 32 ZIs have been functioning with their
      prosthesis. The rate of biologic complications related to ZIs was found 9.3% and
      prosthetic complication's rate related to ZI was 3%. Two early failures of ZIs
      were recorded. Chewing performance (P: 0.003), stability (P: 0.0001), and
      phonetics (P: 0.003) were found higher in hybrid prosthetic group. On the other
      hand, there was a statistically significant difference between groups in favor of
      removable prosthetic group regarding ease of cleaning (P: 0.007). Our study shows
      high success rate and minimal complications for 32 ZIs. This procedure seems to
      be an alternative to the bone grafts or sinus lifting techniques in patient of
      severely resorbed maxilla or to the obturator prosthesis for maxillectomy
      patients.

PMID- 27893563
TI  - Resistance Training Improves Muscle Function and Cardiometabolic Risks But Not
      Quality of Life in Older People With Type 2 Diabetes Mellitus: A Randomized
      Controlled Trial.
AB  - BACKGROUND AND PURPOSE: In older people with type 2 diabetes mellitus (T2DM), the
      effects of aging and T2DM may compromise the function of skeletal muscle,
      deteriorate metabolic status, and jeopardize physical performance, aerobic
      capacity, and quality of life (QoL). The purpose of this study was to investigate
      the effects of 12 weeks of resistance training (RT) on muscle function, physical
      performance, cardiometabolic risks, and QoL in older people with T2DM. METHODS:
      This study was a randomized controlled trial that employed block randomization,
      assessor blinding, and the intention-to-treat principle. Thirty people 65 years
      or older with a diagnosis of T2DM were randomly assigned to either an exercise
      group or a control group and were further stratified by gender. The exercise
      group performed 8 RT exercises in 3 sets of 8 to 12 repetitions at 75% 1
      repetition maximum (1-RM) 3 times per week for 12 weeks. The control group
      received usual care and maintained their daily activities and lifestyle. Muscle
      function (1-RM and muscle oxygenation responses), physical performance (5
      repetition sit-to-stand test and Timed Up and Go test), cardiometabolic risks
      (aerobic capacity, blood pressure, body composition, glycemic control, lipids
      levels, and high-sensitivity C-reactive protein levels), and QoL (Audit of
      Diabetes-Dependent Quality of Life 19) were assessed at baseline (week 0) and
      after the 12-week interventions (week 12). RESULTS: The 1-RM chest-press and leg
      press strength and physical performance in 5-repetition sit-to-stand test were
      significantly improved in the exercise group compared with the controls after the
      interventions. The exercise group had significantly lower resting systolic blood
      pressure (by -12.1 mm Hg, P = 0.036) than did the controls after 12 weeks of RT,
      without any significant within-group change in either group after intervention.
      The waist circumference, fasting glucose levels, and peak diastolic blood
      pressure tended to favor RT over usual care after the interventions. CONCLUSION:
      Twelve weeks of RT increased the maximal strength in chest-press and leg-press
      tests, and improved 5-repetition sit-to-stand performance in older people with
      T2DM. Our study demonstrated that supervised, structured RT was able to promote
      muscle function and alleviate cardiometabolic risks in people with T2DM 65 years
      or older.

PMID- 27893565
TI  - First-Person Perspective Action Observation Training in Individuals With
      Parkinson's Disease: A Consideration-of-Concept Controlled Pilot Trial.
AB  - BACKGROUND AND PURPOSE: Action observation training (AOT) consists of the
      observing of actions performed by others, followed by imitation. Physical therapy
      techniques based on action observation may influence motor performance in
      individuals with idiopathic Parkinson's disease (IPD). OBJECTIVES: The aim of
      this pilot study was to provide a preliminary approach to assess AOT in
      anatomical first-person perspective (FPP) as a rehabilitation technique to
      improve body function and activity in individuals with disability due to IPD.
      METHODS: Videos showing in FPP movements of the upper and lower limbs were
      produced. A research protocol was designed and tested for feasibility. After
      baseline assessment, 16 participants with mild to moderate disability due to IPD,
      all receiving conventional physical therapy group treatment, were nonrandomly
      assigned to either 1 extra hour of individualized FPP AOT per session or
      comparison group. Upper and lower limb functioning, independence in activity of
      daily living, and mobility were assessed before and after training. Data were
      analyzed by descriptive statistics; statistical comparisons were conducted as
      part of the feasibility assessment of the data management plan by means of
      nonparametric tests. RESULTS: A set of 22 videos was created and administered.
      Groups were comparable at baseline assessment. All participants completed the
      study and had complete data. Compared with baseline, both groups improved
      significantly. The experimental group had a better response based on change
      scores, and the differences were large for 3 of the outcome measures. No
      significant between-group differences were observed. DISCUSSION: The equipment
      needed for the production of the videos was easily available. The study protocol
      was successfully implemented. Adherence rates to study procedures were excellent,
      and no adverse events occurred. Differences in methods and participant
      populations prevented comparison in our experimental approach. The number and
      content of videos, and the length of the sessions proposed, was close to that of
      other studies providing an FPP AOT program in individuals with cerebral palsy and
      stroke. Both groups improved and the effect was greater for the experimental one.
      However, no significant difference between the groups was observed. CONCLUSIONS:
      This pilot study suggests that FPP AOT is a feasible intervention and the
      research protocol designed would be suitable, with minor modifications, for the
      conduction of a subsequent stage 2 trial designed to verify the hypothesis that
      the adjunct of FPP AOT might improve motor performance in individuals with IPD.

PMID- 27893564
TI  - Instrumented Test of Sensory Integration for Balance: A Validation Study.
AB  - BACKGROUND AND PURPOSE: Abnormal postural sway is associated with an increase in
      risk of falls but is difficult for clinicians to accurately quantify without
      access to laboratory equipment. Instrumenting clinical outcome measures using
      body-worn movement monitors is a low-cost alternative. This is the first study to
      compare the modified Clinical Test of Sensory Integration for Balance (i-mCTSIB)
      to the laboratory test of the Sensory Organization Test (SOT) with dynamic
      posturography in a group of participants with Parkinson's disease (PD) and subtle
      balance limitations. The purpose of this study was to (1) determine the
      concurrent validity of the i-mCTSIB with the SOT (6 and 4 conditions) and (2)
      compare the i-mCTSIB and the SOT to differentiate between individuals with and
      without recent falls within the previous 6 months. METHODS: This cross-sectional
      study examined 26 participants with idiopathic PD who had a Motor Unified
      Parkinson's Disease Rating Scale score of 32.7 (13.5) out of 108. RESULTS: The
      composite and conditions 1 and 4 of the i-mCTSIB and SOT scores were
      significantly correlated: composite scores r = -0.64 (P <= .001), C1 r = -0.43 (P
      = .03), C3 r = -0.60 (P <= .01), and C4 r = -0.54 (P <= .001). A significant
      difference was observed in mean i-mCTSIB composite scores between fallers and
      nonfallers (P = .04). In contrast, the SOT composite was not significantly
      different between fallers and nonfallers (P = 0.31). DISCUSSION: The results
      suggest that the i-mCTSIB may be a valid and clinically meaningful measure of
      sensory organization in persons with PD, even those with mild postural
      instability as measured by the median Hoehn and Yahr score (2.0). Future research
      should evaluate predictive validity of the i-mCTSIB for prospective falls.
      CONCLUSION: The instrumented mCTSIB with portable, body-worn movement allows
      clinicians to quantify abnormal postural sway without the ceiling effects of
      clinical balance testing or the expense and importability of force plate
      technology in the SOT. Instrumenting mCTSIB may also distinguish between fallers
      and nonfallers.

PMID- 27893566
TI  - Validity and Reliability of a Portable Balance Tracking System, BTrackS, in Older
      Adults.
AB  - BACKGROUND AND PURPOSE: Falls are the leading cause of disability, injury,
      hospital admission, and injury-related death among older adults. Balance
      limitations have consistently been identified as predictors of falls and
      increased fall risk. Field measures of balance are limited by issues of
      subjectivity, ceiling effects, and low sensitivity to change. The gold standard
      for measuring balance is the force plate; however, its field use is untenable due
      to high cost and lack of portability. Thus, a critical need is observed for valid
      objective field measures of balance to accurately assess balance and identify
      limitations over time. The purpose of this study was to examine the concurrent
      validity and 3-day test-retest reliability of Balance Tracking System (BTrackS)
      in community-dwelling older adults. Minimal detectable change values were also
      calculated to reflect changes in balance beyond measurement error. METHODS:
      Postural sway data were collected from community-dwelling older adults (N = 49,
      mean [SD] age = 71.3 [7.3] years) with a force plate and BTrackS in multitrial
      eyes open (EO) and eyes closed (EC) static balance conditions. Force sensors
      transmitted BTrackS data via a USB to a computer running custom software. Three
      approaches to concurrent validity were taken including calculation of Pearson
      product moment correlation coefficients, repeated-measures ANOVAs, and Bland
      Altman plots. Three-day test-retest reliability of BTrackS was examined in a
      second sample of 47 community-dwelling older adults (mean [SD] age = 75.8 [7.7]
      years) using intraclass correlation coefficients and MDC values at 95% CI (MDC95)
      were calculated. RESULTS: BTrackS demonstrated good validity using Pearson
      product moment correlations (r > 0.90). Repeated-measures ANOVA and Bland-Altman
      plots indicated some BTrackS bias with center of pressure (COP) values higher
      than FP COP values in the EO (mean [SD] bias = 4.0 [6.8]) and EC (mean [SD] bias
      = 9.6 [12.3]) conditions. Test-retest reliability using intraclass correlation
      coefficients (ICC2.1 was excellent (0.83) and calculated MDC95 for EO (9.6 cm)
      and EC (19.4 cm) and suggested that postural sway changes of these amounts are
      meaningful. DISCUSSION: BTrackS showed some bias with values exceeding force
      plate values in both EO and EC conditions. Excellent test-retest reliability and
      resulting MDC95 values indicated that BTrackS has the potential to identify
      meaningful changes in balance that may warrant intervention. CONCLUSION: BTrackS
      is an objective measure of balance that can be used to monitor balance in
      community-dwelling older adults over time. It can reliably identify changes that
      may require further attention (eg, fall-prevention strategies, declines in
      physical function) and shows promise for assessing intervention efficacy in this
      growing segment of the population.

PMID- 27893567
TI  - Determining Whether a Dosage-Specific and Individualized Home Exercise Program
      With Consults Reduces Fall Risk and Falls in Community-Dwelling Older Adults With
      Difficulty Walking: A Randomized Control Trial.
AB  - BACKGROUND AND PURPOSE: The development and implementation of effective
      interventions to prevent falls in older adults is a public health priority. The
      purpose of this study was to compare the efficacy of a new practice model,
      incorporating Shubert's evidence-based fall prevention recommendations, with the
      usual ambulatory physical therapy (PT) at Rusk Rehabilitation, to decrease fall
      risk among older adults living in the community. The hypotheses were (1) the
      proposed program would decrease participants' fall risk, (2) it would be more
      effective than our usual PT, and (3) the addition of 4 consults after discharge
      would improve compliance with a home exercise program. METHODS: This was a
      randomized controlled trial. Sixty-nine participants who were independent
      community dwellers, were 65 years or older, had difficulty walking or complaints
      of instability, and had 1 or more risk of falls were randomly assigned into a
      usual care group (UCG, n = 43) or an experimental group (EG, n = 26). Both groups
      received PT 2 times per week for 30 minutes for 10 to 32 visits. The UCG received
      the usual PT delivered at Rusk. The EG was instructed in a moderate- to high
      intensity home exercise program designed after completing the mini-Balance
      Evaluation Systems Test to assist with exercise prescription. The EG was educated
      on performing a recommended dosage of exercise over 6 months using a diary. The
      EG received 4 additional 30-minute consults every 2 to 4 weeks postdischarge to
      reinforce compliance. Self-report of number of falls, number of minutes of
      exercise per week, and performance on outcome measures (Timed Up and Go, 5-times
      sit-to-stand, Berg Balance Scale, and Activity Balance Confidence Scale) were
      monitored at evaluation, 2, 4, and 6 months. RESULTS AND DISCUSSION: Thirty-five
      participants completed the study (UCG n = 22; EG n = 13). Both groups were
      similar at baseline on outcome measures and number of visits. Random effect model
      analyses demonstrated that both groups made significant reductions in fall risk
      over 6 months as identified by performance on outcome measures. However, the EG
      improved significantly more compared with the UCG over time (P < .05). Linear
      regression analyses showed that the EG exercised significantly more compared with
      the UCG at all times (P < .05). The EG exceeded the target of 115 min/wk of
      exercise (154 minutes, standard deviation [SD] 68.5; 170 minutes, SD 96.8; and
      143 minutes, SD 68.5) at 2, 4, and 6 months, respectively. This study
      demonstrated that the experimental program is effective in decreasing fall risk
      in community-dwelling older adults and is more effective than our usual care.
      Moreover, it suggests that the overall experimental protocol may offer an
      effective strategy to foster adherence to an exercise program without the
      increasing number of visits. CONCLUSION: This study supports the efficacy of the
      experimental program in decreasing fall risk and being more effective than our
      usual care, as well as fostering greater compliance with an exercise regimen. It
      provides some preliminary evidence to support Shubert's recommendation on
      exercise prescription for fall prevention.

PMID- 27893568
TI  - Physical Function in Older Adults With Multiple Sclerosis: An Application of the
      Short Physical Performance Battery.
AB  - BACKGROUND AND PURPOSE: There is a growing prevalence of older persons living
      with multiple sclerosis (MS), and this cohort likely undergoes changes in
      physical function associated with MS and its progression as well as those
      associated with normal aging. This cross-sectional study examined physical
      function in a community-dwelling sample of older adults with MS compared with
      matched controls using the Short Physical Performance Battery (SPPB). METHODS:
      The sample (N = 40) included 20 older adults with MS and 20 older adults without
      MS who were matched on sex and age. All participants completed the SPPB. RESULTS:
      Statistically significant differences were observed between groups for the
      overall SPPB score (P = .013; d = 0.45) and the balance (P = .002; d = 0.46) and
      gait speed (P = .009; d = 0.30) component scores. The difference between groups
      in the lower extremity strength component approached significance (P = .056; d =
      0.34). Of note, only 2 older adults without MS had SPPB scores below 10 (ie,
      10%), whereas 8 older adults with MS had SPPB scores below 10 (ie, 40%); this
      represented a statistically significant difference in future risk for disability
      (P = .028). DISCUSSION/CONCLUSIONS: We provide preliminary evidence for reduced
      physical function based on the SPPB as a valid, objective measure of lower
      extremity functional performance among older adults with MS.

PMID- 27893569
TI  - Development and Validation of a Novel Motor-Cognitive Assessment Strategy of
      Compensatory Sit-to-Stand Maneuvers in People With Dementia.
AB  - BACKGROUND AND PURPOSE: People with dementia show disease-specific sit-to-stand
      (STS) movement disorders, which relate to deficits of integrating cognitive
      aspects of motor processes into motor action organization. During STS training in
      rehabilitation therapy, compensatory STS movement maneuvers are taught aiming to
      improve patients' STS ability. Previous clinical STS measures do not address
      these maneuvers or assess cognitive aspects of their motor action organization.
      The purpose of this study was to develop and validate a motor-cognitive STS
      assessment instrument for people with dementia (Assessment of Compensatory Sit-to
      Stand Maneuvers in People With Dementia, ACSID). METHODS: The ACSID covers the
      recall, initiation, and effective performance of compensatory STS movement
      maneuvers. The inter- and intrarater reliability, concurrent validity,
      sensitivity to change, and feasibility were investigated by secondary analysis of
      data of 97 participants from a randomized controlled trial to improve motor
      cognitive performances in people with mild to moderate dementia (mean [standard
      deviation] age: 82.5 [5.9] years, Mini-Mental Status Examination: 21.9 [2.9]
      points). Concurrent validity of the individual ACSID items was assessed against
      reference criteria derived from video-motion analysis. RESULTS: Good to excellent
      inter- (kappa [kappa] = 0.64-0.99; intraclass correlation coefficient [ICC] =
      0.74-0.89) and intrarater (kappa= 0.77-0.91; ICC = 0.77-0.91), concurrent
      validity (point-biserial correlation coefficients = |0.56|-|0.84|), and
      sensitivity to change (standardized response means = 0.61-1.00) were found.
      Feasibility was excellent with a high completion rate (96.9%), no critical events
      during assessment, and no floor or ceiling effects. CONCLUSIONS: The ACSID
      represents the first observation-based assessment instrument to document motor
      and cognitive aspects in the execution of a motor key feature in people with
      dementia, and has been shown to be reliable, valid, feasible, and sensitive to
      intervention-induced changes.

PMID- 27893570
TI  - Nonoperative Treatment of a Tracheocutaneous Fistula in a Burn Patient.
AB  - Tracheocutaneous fistula (TCF) is a complication occurring after decannulation of
      a long-term tracheostomy and can lead to significant morbidity. We describe a
      case of a TCF in a burn patient treated without surgery. No previous cases have
      been described. A 65-year-old woman presented with symptomatic hypertrophic burn
      scar contractures of the anterior neck 6 months after undergoing excision and
      grafting of full-thickness burns to the neck and chest. She had a history of
      tracheostomy placement at the time of burn. Two months later, she was
      decannulated with no evidence of TCF. She subsequently underwent excision of
      hypertrophic burn scar contractures of the neck with placement of bilayer wound
      matrix followed by split-thickness skin grafting. Postoperatively she was noted
      to have a TCF with subgraft emphysema and difficulty in phonation and
      respiration. With local wound care, the TCF closed spontaneously and a new skin
      graft was placed uneventfully. At 18 months postoperatively, fistula closure was
      maintained with good functional and aesthetic outcome. Conservative management of
      an iatrogenic TCF in a burn patient may result in adequate soft-tissue coverage
      and allow for subsequent successful skin grafting. This method affords minimal
      morbidity to the patient and is a viable alternative to more elaborate flap
      reconstruction.

PMID- 27893571
TI  - A Systematic Review of Patient-Reported Outcome Measures Used in Adult Burn
      Research.
AB  - Patient-reported outcome measures (PROMs) are vital for evaluating patient needs
      and therapeutic progress. This review aimed to identify the PROMs used in adult
      burn care and establish their quality. Computerized bibliographic searches of
      Psychinfo, Social Sciences Citation Index, Cinahl, Psycharticles, AMED, Medline,
      and HAPI were used to find English-language articles using English-language PROMs
      from January 2001 to September 2016. Psychometric quality assessment of the PROMs
      was conducted. A total of 117 studies achieved the entry criteria and reported
      using 77 different PROMs (71 generic and 6 burn-specific). Overall, the
      psychometric quality of the PROMs was low; only 17 (13 generic and 4 burn
      specific) had psychometric evidence appropriate to adults with burn injuries
      completing an English language version of the PROM. Although this review
      identified a number of generic and burn-specific PROMs that have some
      psychometric evidence with adult burn patients, research is still needed to
      further examine these preexisting measures and validate them in different
      languages. This will enable researchers and clinicians to better understand the
      potential impact of a burn injury on adults, and evaluate the effectiveness of
      therapeutic interventions.

PMID- 27893572
TI  - Pain Management in Pediatric Burn Patients: Review of Recent Literature and
      Future Directions.
AB  - Childhood burns are a profoundly traumatic and painful experience. Despite
      recognition of the prevalence of burn injuries in children and the severity of
      the associated pain, burn pain remains undertreated. At the same time, more
      evidence is emerging to suggest that undertreated pain has serious long-term
      medical and psychiatric consequences, many of which can be ameliorated with
      improved pain control. Pain in burn patients is, however, notoriously difficult
      to treat, perhaps because there is a chronic pain aspect underlying the acute
      pain that accompanies wound care and procedures. This difficulty is compounded by
      the fact that there are little data to guide decision making in these patients.
      This article aims to identify the best strategies to guide clinical practice
      through a review of the past 10 years' development in pediatric burn pain
      management. However, because clinical investigations remain limited in burned
      children, we also aim to draw attention to those areas where the data do not
      identify an optimal approach and further work is needed. Overall, in addition to
      just the traditional pharmacological approaches to pain, such as acetaminophen,
      benzodiazepines, and opioids, there is growing evidence to support more
      widespread use of regional anesthesia and novel technologies such as virtual
      reality. Starting with an improved understanding of the current state of the
      literature, we can identify areas of research and important questions whose
      answers will ultimately improve care and reduce suffering for this unfortunate
      population of children.

PMID- 27893573
TI  - Suicide and Fire: A 20-Year Study of Self-Immolation Death in Sousse, Tunisia.
AB  - Self-immolation is a self-destructive conduct described since antiquity. Its
      frequency is variable from one country to another and it is a real public health
      problem in parts of the world. In Tunisia, after the 2011 revolution the problem
      of self-immolation protest has been highly publicized giving the impression of an
      increase in this phenomenon. This is a retrospective analysis of all fatal self
      immolation cases, collected over a 20-year period (1996-2015) at the Forensic
      Medicine Department of the Farhat Hached University Hospital, Sousse, Tunisia. A
      total of 41 cases were collected, of which 23 were men (56%). The mean age was
      36.1 years. Prior to 2011, 78.9% of the victims of self-immolation were women and
      after 2011, 86.4% were men. The rural origin of the victims was found in 56.25%
      of the cases. History of psychiatric illness was found in four individuals. The
      self-immolation took place in the victims' homes in 19 cases (46.3%). It came
      after a conjugal or family conflict in 14 cases (34.1%) and it is of protest
      character in 8 cases (19.5%). This study confirmed the increasing frequency of
      self-immolation in Tunisia after the 2011 revolution and noted a change in the
      victims' profiles.

PMID- 27893574
TI  - Randomized Comparison of Packed Red Blood Cell-to-Fresh Frozen Plasma Transfusion
      Ratio of 4: 1 vs 1: 1 During Acute Massive Burn Excision.
AB  - This prospective randomized controlled trial compared 1:1 vs 4:1 packed red blood
      cell with fresh frozen plasma (PRBC/FFP) transfusion strategy on outcomes in
      children with >20% TBSA burns. Children with >20% TBSA burns were randomized to a
      1:1 or 4:1 PRBC/FFP transfusion ratio during burn excision. Parameters measured
      included demographics, TBSA burn, and Pediatric Risk of Mortality scores.
      Laboratory values recorded preoperatively, 1 hour, 12 hours, 24 hours, and 1 week
      postoperatively included prothrombin time, partial thromboplastin time (PTT),
      international normalized ratio, fibrinogen, protein C, and antithrombin C (AIII).
      Total number of blood products transfused intraoperatively and during
      hospitalization was recorded. Forty-five children were enrolled, 22 in the 1:1
      and 23 in the 4:1 group. Groups were similar in age, TBSA, and Pediatric Risk of
      Mortality score. Preoperative fibrinogen, AIII, protein C, hemoglobin, PTT,
      international normalized ratio, and platelets were similar. In the first two
      excisions, the 1:1 group received significantly more FFP per patient. Volume of
      PRBC and overall product transfused did not differ between groups. At 1 hour
      postoperatively, prothrombin time and PTT were lower and protein C and AIII were
      higher in the 1:1 group. The 4:1 group was more significantly acidotic 1 hour
      postexcision. A 1:1 PRBC/FFP transfusion strategy, compared with a 4:1 strategy,
      decreased postoperative markers of coagulopathy and acidosis immediately after
      surgery. The strategy did not change the total volume of blood product
      transfused. This interim analysis was not powered to detect differences in wound
      healing and length of stay.

PMID- 27893575
TI  - Variations in Burn Excision and Grafting: A Survey of the American Burn
      Association.
AB  - It is unknown whether variations in burn care affect outcomes or affect the
      success of emerging therapeutics. The purpose of this study was to assess burn
      surgeons' preferences in excision and grafting to determine if surgical technique
      affects outcomes. A 71-item survey evaluating skin grafting techniques and
      preferences was emailed to members of the American Burn Association in July and
      August 2015. The survey was anonymous and voluntary. Relationships between
      variables were evaluated using Fisher's exact test. A P-value of <=.05 was deemed
      statistically significant. The survey was sent to 607 burn surgeons, and the
      response rate was 24%. Clinical judgment is the most widely used method to
      determine depth of injury. Surgeons who practice in the United States and
      surgeons who are board certified in general surgery are more likely to determine
      depth of the burn based on clinical judgment alone (P < .001). Fifty-six percent
      of surgeons will perform excision as early as postburn day 1 and 73% will excise
      greater than 20% TBSA in one setting. Surgeons at centers with bed number of <=10
      (P = .024) or surgeons with board certification in plastic surgery (P = .008) are
      more likely to excise deep partial-thickness burns with an attempt to retain
      viable dermis. Geographic location, board certification, and burn unit size all
      contribute to variations in practice. Strong individual preferences make
      standardization of therapies challenging and may affect the success of new
      technologies. Burn surgery continues to be an art as much as a science, and
      accurate documentation of techniques and outcomes is essential for optimizing
      successes and documenting failures of new treatment methods.

PMID- 27893576
TI  - The Use of a Burn Surgery Technique to Improve Wounds Healing in Epidermolysis
      Bullosa.

PMID- 27893577
TI  - A Novel Classification System for Injuries After Electronic Cigarette Explosions.
AB  - Electronic cigarettes (e-cigarettes) contain lithium batteries that have been
      known to explode and/or cause fires that have resulted in burn injury. The
      purpose of this article is to present a case study, review injuries caused by e
      cigarettes, and present a novel classification system from the newly emerging
      patterns of burns. A case study was presented and online media reports for e
      cigarette burns were queried with search terms "e-cigarette burns" and
      "electronic cigarette burns." The reports and injury patterns were tabulated.
      Analysis was then performed to create a novel classification system based on the
      distinct injury patterns seen in the study. Two patients were seen at our
      regional burn center after e-cigarette burns. One had an injury to his thigh and
      penis that required operative intervention after ignition of this device in his
      pocket. The second had a facial burn and corneal abrasions when the device
      exploded while he was inhaling vapor. The Internet search and case studies
      resulted in 26 cases for evaluation. The burn patterns were divided in direct
      injury from the device igniting and indirect injury when the device caused a
      house or car fire. A numerical classification was created: direct injury: type 1
      (hand injury) 7 cases, type 2 (face injury) 8 cases, type 3 (waist/groin injury)
      11 cases, and type 5a (inhalation injury from using device) 2 cases; indirect
      injury: type 4 (house fire injury) 7 cases and type 5b (inhalation injury from
      fire started by the device) 4 cases. Multiple e-cigarette injuries are occurring
      in the United States and distinct patterns of burns are emerging. The
      classification system developed in this article will aid in further study and
      future regulation of these dangerous devices.

PMID- 27893579
TI  - The Psychological Impact of First Burn Camp in Nicaragua.
AB  - Asociacion Pro-Ninos Quemados de Nicaragua (APROQUEN) is a comprehensive burn
      center that provides a holistic and integrated approach to treating burns.
      APROQUEN has set the standards internationally with acute treatment for burns,
      intensive care, reconstructive surgeries, nutritional care, rehabilitation,
      occupational therapy, and psychological treatment. APROQUEN is excelling within
      Central and South America with life-saving techniques and quality of care. It is
      imperative that burn centers in Central America recognize that the treatment of a
      child with a burn injury surpasses physical care to include psychological
      treatment for the complete well-being of the child. It is necessary to provide
      the tools necessary to reintegrate the child back into their environment.
      APROQUEN developed and implemented the first burn camp in Latin America, "Confio
      en Mi" (I trust myself). The camp theme focused on self-esteem. The camp program
      included theory (educational) and practice (applied) components where the campers
      through "classroom type" activities had the opportunity to reflect and share with
      other campers and camp staff on self-esteem, depression, and anxiety.
      Participants were children who survived major burns (N = 33; 58% women; ages 12
      25; 61% <18) and were shown to have difficulty socializing. Comprehensive
      interviews were conducted to ensure fit for camp. Forty-two percent of the
      campers had not slept away from home since the burn injury. Mean TBSA = 20% and
      mean age at time of burn injury was 13. The majority of campers (46%) endured
      flame burn injuries, with 24% having scald injuries. Mean years postburn = 4.8 +
      3.2. Most campers (40%) were enrolled in secondary school, 30% in elementary
      school, and 21% in college. Standardized measures (CDI-2 Parent Form and Child
      Form, Rosenberg Scale, APROQUEN Burn Camp Measure Parent and Child Form, Beck
      Anxiety Inventory, and Beck Depression Inventory) were given to all campers prior
      to attending camp. The same measures were given 2 weeks after the camp and again
      at 6 months. Paired samples' t-tests were conducted and significance was set at P
      <.05. The results indicate that Camp Confio en Mi had a significant impact on
      campers' level of anxiety, depression, and self-esteem. Future burn camps are an
      important part of the continued advancement of postpediatric burn care in
      Nicaragua. This study reveals the importance of future researches necessity to
      focus on generalizing the results of this study to other children who have
      experienced similar burn injuries.

PMID- 27893578
TI  - Propylthiouracil-Associated Leukocytoclastic Necrotizing Cutaneous Vasculitis: A
      Case Report and Review of the Literature.
AB  - The purpose of this case report and review of the literature is to provide an
      exploration of the clinical symptoms, diagnosis, prevention, and management of
      propylthiouracil (PTU)-associated vasculitis in the intensive care setting. A
      PubMed search of the available literature was conducted using the MeSH search
      terms "propylthiouracil" and "vasculitis." The literature search returned 121
      articles. Twenty-five were excluded because they were not in English. Fifty-nine
      case reports or case studies describing PTU-associated vasculitis were included.
      Data extracted from each case study included patient age, sex, autoimmune
      markers, laboratory tests, length of time on PTU, treatment for vasculitis, and
      patient outcomes. The authors reviewed 128 cases of PTU-associated vasculitis.
      The majority were women (8.8:1 F:M ratio), and the most common presenting
      symptoms were rash (51.6%), fever (46.9%), and arthralgia (43.8%). In addition to
      discontinuing PTU, the most common treatment was steroids (71.9%). Eight patients
      (6.3%) progressed to end-stage renal disease; two (1.6%) required intubation for
      respiratory failure; and five (3.9%) died of various organ systems failure
      related to vasculitis development. A high index of suspicion for vasculitis
      should be maintained, especially when presented with skin manifestations in the
      presence of PTU therapy. Screening with myeloperoxidase-antinuclear cytoplasmic
      antibodies is most sensitive. Positive screening should prompt a thorough
      clinical investigation. In cases of severe skin manifestations, the focus should
      be on aggressive wound care. Our case report is unique, not only in the size and
      extent of cutaneous involvement, but also as the first description of mortality
      secondary to cutaneous manifestations.

PMID- 27893580
TI  - The Effects of Adipose-Derived Stem Cell-Differentiated Adipocytes on Skin Burn
      Wound Healing in Rats.
AB  - Both adipose-derived stem cells (ADSCs) and fat grafting promote burn wound
      healing, but whether adipogen-derived cells using various inducers such as 3
      isobutyl-1-methylxanthine (IBMX) and insulin affect wound healing is unknown.
      Herein, ADSC-differentiated adipogenic lineages were used in rat burn wounds to
      evaluate wound healing potential. ADSCs were cultivated using six different
      adipogenic differentiation conditions (IBMX +/- insulin, IBMX for 5 days, high
      and low Dulbecco's modified Eagle's medium) and in vitro morphological changes
      and cell proliferations during adipogenic differentiation were recorded.
      Intermediate burn wounds were inflicted in 15 Wistar male rats. Afterwards, the
      rats were divided into five groups for subcutaneous injections under the wounds:
      control; ADSCs; differentiated adipocytes (-IBMX+INSULIN and +IBMX[D1-5]+INSULIN)
      and fat prepared by Coleman technique. Macroscopic changes and histology were
      documented for 3 weeks. Repeated measures analysis of variance was performed to
      analyze cell growth and wound healing with a statistical level set of P < .05.
      Induction cocktails significantly reduced proliferation and induced lipid droplet
      accumulation. Conditioning without insulin induced the least lipid accumulation,
      while discontinuing IBMX generated larger adipocytes (P < .001). Adipogenic
      differentiated ADSCs had similar wound healing abilities with ADSC and fat
      injections, but differentiated adipocytes (+IBMX[D1-5]+INSULIN) and fat grafting
      accelerated the early healing process relative to ADSC (P < .001). Reduced
      fibrosis and mild inflammatory infiltration limited to superficial dermis were
      observed in +IBMX(D1-5)+INSULIN and fat injection groups, while those reactions
      were mild to moderate in ADSC group. Differentiated adipocytes achieve similar
      wound healing results compared with ADSC and fat injections, but differentiated
      adipocytes (+IBMX[D1-5]+INSULIN) and fat grafting accelerate early healing
      relative to ADSC.

PMID- 27893581
TI  - The Effect of Socioeconomic Status and Parental Demographics on Activation of
      Department of Child and Family Services in Pediatric Burn Injury.
AB  - Burns resulting from child maltreatment are tragic causes of significant
      morbidity and mortality, most commonly affecting children under 3 years of age.
      More than one third of nonaccidental burns occur in single-parent homes or have
      parents with history of mental illness, substance abuse, incarceration, or
      Department of Children and Family Services (DCFS) involvement. The authors sought
      to profile pediatric burn injuries associated with DCFS investigations. They
      performed a retrospective chart review of pediatric burn patients, admitted
      between January 1, 2011 and December 31, 2014. They analyzed patient and
      household demographics, family composition, employment, zip code, insurance,
      etiology, percent TBSA burned, surgical interventions, length of hospital stay,
      disposition, prior DCFS involvement, and DCFS investigation outcomes. There were
      126 DCFS investigations involving patients with average age of 2.6 +/- 3.2 years
      and 5 +/- 5.6% TBSA burn. Scalds were the most prevalent etiology at 76%. Parents
      involved with DCFS were 5 years younger than those without DCFS. Factors
      associated with increased odds of DCFS investigation were non-Caucasian race,
      single-parent homes, unemployed primary caretaker, Medicaid utilization, and
      prior DCFS involvement. A majority of DCFS investigations were initiated at
      outside hospitals, and they found one third to be substantiated cases of abuse.
      Non-Caucasian children, under 3 years of age, from lower socioeconomic or single
      parent homes, are associated with higher rates of DCFS investigations. The
      majority of DCFS investigations were unsubstantiated and there were no
      significant epidemiological differences between unsubstantiated and substantiated
      cases of abuse. Improved understanding of sociodemographic risk factors for
      children at higher risk for negligence or intentional abuse warrants focused
      public health programs on regional prevention and education.

PMID- 27893582
TI  - Basic Burns Management E-Learning: A New Teaching Tool.
AB  - Burns teaching is organized only in a few medical schools in the United Kingdom.
      An e-learning tutorial was developed with the objective of incorporating burns
      teaching within the medical school curriculum. A 33-webpage e-learning was
      created, covering topics such as local and general response to burns, assessment
      of burns, first aid, primary and secondary survey, and referral guidelines.
      Medical student satisfaction was then evaluated using a 12-question feedback
      survey rated based on a Likert scale from 1 (very poor) to 5 (very good). The 12
      question survey was completed by a total of 18 medical students ranging from
      second to fourth years (second = 17%, third = 22%, fourth = 61%). While only a
      couple of students had received prior burns teaching, 50% of the cohort had an
      interest to pursue surgery as a career. The majority of students (72%) would be
      interested to have an e-learning module on basic burns management in their
      medical curriculum. The means of all domains specific to the e-learning were
      rated as "good" or "very good." Students' rating for ease of use was 87%,
      usefulness was 88%, relevance to the medical curriculum was 90%, clarity and
      quality of content were 78% and 83%, respectively, design was 79%, and the
      overall satisfaction with this e-learning was 87%. The "Basic Burns Management" e
      learning tutorial can provide an efficient and effective means of information
      delivery to medical students and junior doctors, allowing easy and fast
      incorporation of burns teaching within the medical curriculum and in other
      medical teaching settings.

PMID- 27893583
TI  - Retinal Vessel Oxygen Saturation and Vessel Diameter in Inactive Graves
      Ophthalmopathy.
AB  - PURPOSE: To investigate whether inactive thyroid-associated ophthalmopathy (TAO)
      affects retinal oxygen saturation and/or vessel diameter. METHODS: Via an
      observational case-control study, retinal circulation was measured in patients
      with inactive TAO (mild, moderate, and severe) and normal subjects by retinal
      oximetry. Complete ophthalmologic examination, including noncontact tonometry and
      Hertel exophthalmometry, was performed; history of smoking and dysthyroid disease
      were recorded. Analysis of variance or the Kruskal-Wallis test was used to
      compare oximetry values between TAO and controls. Simple linear regression was
      used to analyze the correlation of Hertel, smoking, and intraocular pressure with
      oximetry values. RESULTS: Seventy-six eyes were enrolled: 19 controls, and 17
      mild, 21 moderate, and 19 severe inactive TAO. Retinal oxygen saturation did not
      change significantly in inactive TAO versus controls; arteriole saturation:
      severe, 95.7% +/- 7.0%; moderate, 93.2% +/- 3.9%; mild, 90.3% +/- 4.8%; and
      controls, 93.1% +/- 6.4%; vein saturation: severe, 57.4% +/- 7.1%; moderate,
      59.0% +/- 7.0,; mild, 56.3% +/- 7.9%; and controls, 58.5% +/- 6.5%; arteriovenous
      saturation: severe, 38.3% +/- 8.0%; moderate, 34.2% +/- 7.1%; mild, 33.9% +/-
      6.8%; and controls, 34.6% +/- 5.9%. However, retinal venous diameter with severe
      TAO (137.3 +/- 12.5 MUm) significantly decreased in comparison with controls
      (148.8 +/- 10.2 MUm, p = 0.017). Otherwise, no significant change in vessel
      diameter was found between TAO and controls. No statistically significant
      correlations were found between Hertel values or intraocular pressure and
      oximetry values. However, there was a positive significant correlation between
      smoking and arteriovenous oxygen saturation (p = 0.017, beta = 4.61).
      CONCLUSIONS: In inactive TAO versus controls, retinal oxygen saturation
      fluctuated and could be affected by smoking; however, the retinal venous diameter
      only decreased significantly for severe TAO. This implies that TAO may affect
      retinal circulation; this effect could be accelerated by smoking.

PMID- 27893584
TI  - Facial Pyoderma Gangrenosum Presenting With Cranial Nerve VII Palsy and
      Cicatricial Ectropion.

PMID- 27893585
TI  - Conjunctival Melanoma Responsive to Combined Systemic BRAF/MEK Inhibitors.
AB  - This report demonstrates a unique case of conjunctival melanoma harboring a BRAF
      V600E mutation responsive to systemic therapy with BRAF and MEK inhibitors. While
      systemic therapy would not be appropriate in patients with local disease alone,
      it may act therapeutically in cases of higher stage ocular surface and eyelid
      melanoma.

PMID- 27893586
TI  - Spiritual Immersion: Developing and Evaluating a Simulation Exercise to Teach
      Spiritual Care to Undergraduate Nursing Students.
AB  - This article describes the development, implementation, and evaluation of a
      simulation exercise designed to teach spiritual care to prelicensure nursing
      students. Participation in a spiritual care simulation resulted in improved
      knowledge and attitudes relating to spirituality and spiritual care. The results
      from this study demonstrate the value of using simulation and spiritual
      assessment to teach students how to recognize and respond therapeutically to
      spiritual needs.

PMID- 27893587
TI  - Measuring Childhood Adversity in Life Course Cardiovascular Research: A
      Systematic Review.
AB  - OBJECTIVE: Identifying the life course health effects of childhood adversity is a
      burgeoning area of research, particularly in relation to cardiovascular disease
      (CVD). However, adversity measurement varies widely across studies, which may
      hamper our ability to make comparisons across studies and identify mechanisms
      linking adversity to CVD. The purposes of this review are to summarize adversity
      measurement approaches in the context of CVD, identify gaps, and make
      recommendations for future research. METHODS: PubMed and PsycINFO searches were
      conducted through June 2016. Studies were selected if CVD end point or predisease
      risk markers were investigated in association with a measure of childhood
      adversity. Forty-three studies were reviewed. A meta-analysis was not conducted
      because of the variation in exposures and outcomes assessed. RESULTS: Adversity
      measurement was heterogeneous across studies. Metrics included different sets of
      adverse events, relational factors, and socioeconomic indicators. Thirty-seven
      percent measured childhood adversity prospectively, 23% examined a CVD end point,
      and 77% treated adversity as an unweighted summary score. Despite the
      heterogeneity in measurement, most studies found a positive association between
      childhood adversity and CVD risk, and the association seems to be dose-response.
      CONCLUSIONS: The literature on childhood adversity and CVD would benefit from
      improving consistency of measurement, using weighted adversity composites,
      modeling adversity trajectories over time, and considering socioeconomic status
      as an antecedent factor instead of a component part of an adversity score. We
      suggest conceptual and analytic strategies to enhance, refine, and replicate the
      observed association between childhood adversity and CVD risk.

PMID- 27893588
TI  - Suite PET/CT neuroimaging for the diagnosis of Parkinson's disease: statistical
      parametric mapping analysis.
AB  - OBJECTIVES: The aim of this study was to investigate the topographical
      distribution of dopamine transporter (DAT), dopamine D2 receptor, and glucose
      metabolism in Parkinson's disease (PD) using PET/computed tomography (CT)
      scanning and statistical parametric mapping (SPM) analysis. PARTICIPANTS AND
      METHODS: Seventy-four patients (58 PD patients and 16 normal controls) underwent
      DAT, D2 receptor, and glucose brain PET/CT scans using C-methyl-N-2-beta
      carbomethoxy-3-beta-(4-fluorophenyl) tropane (C-beta-CFT), C-raclopride (C-RAC),
      and fluorine-18-fluorodeoxyglucose (F-FDG) radiotracers for the respective scans.
      All three PET/CT procedures were performed in each participant. The uptake
      patterns were analyzed using SPM software. RESULTS: Striatal DAT binding was
      lower in PD patients than in controls, whereas D2 receptor binding did not differ
      between PD patients and controls. D2 receptor binding was increased in the
      putamen in only the 12 drug-naive patients. Glucose uptake was also slightly
      lower in the cingulate gyrus of PD patients than in the controls. CONCLUSION:
      Suite PET/CT scans using the ligands C-beta-CFT, C-RAC, and F-FDG PET/CT are
      valuable for diagnosing PD. SPM-based analysis of static PET/CT scan data is
      potentially of great clinical use.

PMID- 27893589
TI  - The role of PSMA PET/CT imaging in restaging of prostate cancer patients with low
      prostate-specific antigen levels.
AB  - INTRODUCTION: Prostate-specific membrane antigen (PSMA) is increasingly being
      recognized as a novel target for the PET imaging of prostate cancer (PCa) and Ga
      DKFZ-11 (Ga-PSMA) has been suggested as a novel tracer for detection of PCa
      relapses and metastases. The aim of this study was to evaluate the diagnostic
      value of PSMA PET/CT in the diagnosis of recurrent PCa with low prostate-specific
      antigen (PSA) levels. PATIENTS AND METHODS: We carried out a retrospective
      analysis of patients who underwent PSMA PET/CT from November 2013 to December
      2014 in our department. Among these patients, 50 out of 178 who had increasing
      PSA levels (<5 ng/ml) and did not have known metastasis were included in this
      study. RESULTS: Patients had an average PSA of 1.41 ng/ml. A total of 29 patients
      (58%) showed at least one positive lesion. PET positivity rates of 31% (n=4), 54%
      (n=13), and 88% (n=14) were observed in patients with a PSA level of less than
      0.2, 0.2-2, and 2-5 ng/ml, respectively. A positive correlation was observed
      between positivity rate and Gleason scores and blood PSA levels. Verification was
      performed in 46 patients, with biopsy (n=3) and follow-up, and conventional
      imaging studies at the time of the PET/CT or during follow-up with a mean period
      of 10.6+/-3.3 months and ranged from 3.8 to 16.4 months. According to patient
      based analysis of 46 cases, 57% of patients had true positive, 24% of patients
      had true negative, 2% of patients had false positive, an 18% of patients had
      false-negative findings. A sensitivity of 76.47% (95% confidence interval: 58.83
      89.25%) and a specificity of 91.67% (95% confidence interval: 61.52-99.79%) were
      found. CONCLUSION: PET/CT with Ga-PSMA is a valuable tool for assessing
      recurrence of PCa with a high sensitivity in patients who have PSA levels between
      0.2 and 5 ng/ml. In addition, this study suggests that PSMA PET/CT can be used in
      patients with very low (<0.2 ng/ml) but increasing PSA levels, which, in many
      cases, may influence further clinical management.

PMID- 27893590
TI  - Association study of the GLRX5 rs1007814 polymorphism with schizophrenia in the
      Han Chinese population.

PMID- 27893591
TI  - ENDOPHTHALMITIS IN A PATIENT TREATED WITH BACILLUS CALMETTE-GUERIN IMMUNOTHERAPY.
AB  - BACKGROUND: Intravesical Bacillus Calmette-Guerin (BCG) instillation has become
      one of the mainstays of adjunctive therapy in the treatment of superficial
      bladder cancer. Ophthalmologic complications are rare, but few cases are reported
      in the literature. METHODS: Retrospective observational case report. RESULTS: The
      authors report a case of unilateral Mycobacterium bovis BCG endophthalmitis after
      intravesical BCG instillations. Despite appropriate systemic antituberculous and
      corticosteroid therapy, the patient almost completely lost sight in the affected
      eye. This is the fourth case in the literature of proven M. bovis endophthalmitis
      suggesting a direct choroidal mycobacterial infection and not only a
      hypersensitivity immunologic reaction as previously suggested. CONCLUSION: This
      case highlights the direct choroidal mycobacterial infection of the disease after
      BCG instillations for bladder cancer and failure of treatment despite culture
      proven drug sensitivity, thus suggesting the need to revaluate adequate treatment
      to avoid loss of vision.

PMID- 27893592
TI  - COUGHING-INDUCED SUPRACHOROIDAL HEMORRHAGE SIMULATING MELANOMA IN TWO CASES.
AB  - PURPOSE: To describe two cases of coughing-induced suprachoroidal hemorrhage
      referred as choroidal melanoma. METHODS: Observational case reports. RESULTS: Two
      female patients (ages 54 and 60 years) were referred with possible choroidal
      melanoma. Both gave a history of 1 day of heavy coughing with Valsalva maneuver
      within 2 weeks before discovery of the tumor. In one case, the patient used
      anticoagulants for aortic valve replacement and the other patient used antiasthma
      medications. One patient noted sharp ocular pain one week before presentation to
      this service. In both cases, the choroidal lesion was at the globe equator, near
      a vortex ampulla, and appeared homogeneously dark brown and with acoustic
      hollowness on ultrasonography, concerning for choroidal melanoma. However,
      neither lesion demonstrated intrinsic vascularity on fluorescein angiography or
      indocyanine angiography. Both lesions showed isoautofluorescence and optical
      coherence tomography evidence of shallow choroidal folds with inner choroidal
      elevation over a dome-shaped, optically-lucent deep choroidal mass, consistent
      with suprachoroidal hemorrhage. Fine needle aspiration biopsy in 1 case confirmed
      blood without melanoma. Both cases were observed with complete spontaneous
      resolution of the hemorrhage and normal-appearing choroid within 2 months.
      CONCLUSION: Coughing-induced suprachoroidal hemorrhage can simulate melanoma.
      Clinical and imaging features can assist in diagnosis. The hemorrhage generally
      resolves within few months.

PMID- 27893593
TI  - Trends in Selected Measures of Racial and Ethnic Disparities in Gonorrhea and
      Syphilis in the United States, 1981-2013.
AB  - BACKGROUND: The purpose of this study was to examine selected measures of racial
      and ethnic disparities in the reported incidence of syphilis and gonorrhea from
      1981 to 2013 in the United States. METHODS: For each year, from 1981 to 2013, we
      calculated values for 5 disparity measures (Gini coefficient, 2 versions of the
      index of disparity, population attributable proportion, and the black-to-white
      rate ratio) for 5 racial/ethnic categories (non-Hispanic white, non-Hispanic
      black, Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander). We
      also examined annual and 5-year changes to see if the disparity measures agreed
      on the direction of change in disparity. RESULTS: With a few exceptions, the
      disparity measures increased from 1981 to 1993 and decreased from 1993 to 2013,
      whereas syphilis and gonorrhea rates decreased for most groups from 1981 to 1993
      and increased from 1993 to 2013. Overall, the disparity measures we examined were
      highly correlated with one another, particularly when examining 5-year changes
      rather than annual changes in disparity. For example, all 5 measures agreed on
      the direction of change in the disparity of syphilis in 56% of the annual
      comparisons and in 82% of the 5-year comparisons. CONCLUSIONS: Although the
      disparity measures we examined were generally consistent with one another, these
      measures can sometimes yield divergent assessments of whether racial/ethnic
      disparities are increasing or decreasing for a given sexually transmitted disease
      from one point in time to another, as well as divergent assessments of the
      relative magnitude of the change.

PMID- 27893594
TI  - Sexually Transmitted Disease Program Evolution in Response to Changes in the
      Public Health Environment: A Massachusetts Example.
AB  - BACKGROUND: In 2008, the line item supporting sexually transmitted disease (STD)
      services in the Massachusetts state budget was cut as a result of budget
      shortfalls. Shortly thereafter, direct provision of STD clinical services
      supported by the Massachusetts Department of Public Health (MDPH) was suspended.
      Massachusetts Department of Public Health requested an initial assessment of its
      internal response and impact in 2010. A follow-up assessment occurred in
      September 2013. METHODS: In 2010 and 2013, 39 and 46 staff, respectively, from
      MDPH and from clinical partner agencies, were interviewed about changes in the
      role of the MDPH, partnerships, STD services, challenges, and recommendations.
      Interview notes were summarized, analyzed, and synthesized by coauthors using
      qualitative analysis techniques and NVivo software. RESULTS: The withdrawal of
      state funding for STD services, and the subsequent reduction in clinical service
      hours, erected numerous barriers for Disease Intervention Specialists (DIS)
      seeking to ensure timely STD treatment for index cases and their partners. After
      initial instability, MDPH operations stabilized due partly to strong management,
      new staff, and intensified integration with human immunodeficiency virus
      services. Existing contracts with human immunodeficiency virus providers were
      leveraged to support alternative STD testing and care sites. Massachusetts
      Department of Public Health strengthened its clinical and epidemiologic
      expertise. The DIS expanded their scope of work and were outposted to select new
      sites. Challenges remained, however, such as a shortage of DIS staff to meet the
      needs. CONCLUSIONS: Although unique in many ways, MA offers experiences and
      lessons for how a state STD program can adapt to a changing public health
      context.

PMID- 27893595
TI  - The Impact of Prescriptions on Sex Partner Treatment Using Expedited Partner
      Therapy for Chlamydia trachomatis Infection, New York City, 2014-2015.
AB  - BACKGROUND: Chlamydia trachomatis reinfections, often resulting from resuming sex
      with untreated partners, can increase the risk of pelvic inflammatory disease,
      infertility, and ectopic pregnancy. Expedited partner therapy (EPT) has been
      shown to prevent reinfection when provided as medication (Medication-EPT) that
      patients give to sex partners; however, EPT is often provided as a prescription
      (Prescription-EPT). We compared partner treatment outcomes for Medication-EPT
      versus Prescription-EPT. METHODS: We conducted telephone interviews from October
      2014 to October 2015 with a population-based random sample of women aged 15 to 25
      years diagnosed with Chlamydia trachomatis. Interview questions included:
      demographics, patient-treatment, EPT type, and patient report of partner
      treatment. The main outcomes explored were: proportion of women receiving EPT,
      proportion of Prescription-EPT and Medication-EPT, and proportion of partners
      reported as treated. We used chi and Fisher exact tests for analysis. RESULTS: A
      total of 421 women completed the interview; 357 (84.8%) of 421 women reported
      having been treated, and 109/357 (30.5%) received EPT for any partner. Women
      given a prescription (vs medication) for their own treatment were more likely to
      receive EPT (odds ratio, 1.57; P = 0.05) and to receive Prescription-EPT
      specifically (odds ratio, 6.85; P < 0.0001). Forty-eight (52.2%) of 92 patients
      who received EPT for their most recent partner received Prescription-EPT. There
      was no difference by EPT type in proportion of index patients reporting partner
      treatment: 77.1% (37/48) for Prescription-EPT versus 79.5% (35/44) for Medication
      EPT (P > 0.05). CONCLUSIONS: Prescription-EPT and Medication-EPT appear to result
      in comparable rates of partner treatment. Further research is needed to assess
      the effects of Prescription-EPT on partner treatment among adolescents and in
      other contexts.

PMID- 27893596
TI  - Pharmacists' Knowledge and Practices Surrounding Expedited Partner Therapy for
      Chlamydia trachomatis, New York City, 2012 and 2014.
AB  - BACKGROUND: Health care providers in New York City can prescribe treatment for
      Chlamydia trachomatis (Ct) for a patient's partner without the partner having a
      medical evaluation ("prescription-expedited partner therapy" [EPT]), and use of
      prescription-EPT is common. However, there is little known about pharmacists'
      knowledge and practices surrounding EPT. METHODS: Two cross-sectional surveys, in
      2012 and 2014, were conducted with representative samples of supervising
      pharmacists in NYC neighborhoods with high rates of Ct infection. RESULTS: In
      both survey years, the majority of pharmacists who agreed to participate returned
      a survey (2012: 81% [83/103], 2014: 61% [106/173]), and pharmacist and pharmacy
      characteristics were similar across the 2 surveys. Pharmacists' EPT-related
      knowledge and practice was generally low, with little change between 2012 and
      2014. In both years, fewer than half of pharmacists knew EPT was legal (2012,
      46%; 2014, 42%). There were even decreases in specific content knowledge; in
      2014, significantly fewer of the pharmacists who knew EPT was legal, knew that
      the initials "EPT" must be written in the body of the prescription (2012: 58%;
      2014: 36%, P < 0.05). Most pharmacists in both survey years reported they had
      never received an EPT prescription, and those who had reported only infrequent
      receipt. CONCLUSIONS: NYC pharmacists had low levels of knowledge and familiarity
      with EPT law and reported infrequent receipt of EPT prescriptions. Pharmacists
      and providers should be further educated about EPT laws and regulations so that
      prescription-EPT use can be accurately monitored, and to assure the success of
      this partner treatment strategy.

PMID- 27893597
TI  - Partner Notification Outcomes for Men Who Have Sex With Men Diagnosed With
      Syphilis Referred to Partner Notification Officers, Melbourne, Australia.
AB  - BACKGROUND: We examined the extent of partner notification for men who have sex
      with men (MSM) who were diagnosed with syphilis, and offered referral to a
      partner notification officer (PNO), to assist them with informing recent sexual
      partners. METHODS: Between October 2013 and March 2015, MSM diagnosed with
      syphilis at the Melbourne Sexual Health Centre were routinely offered a referral
      to a PNO. The outcomes of this intervention were evaluated including the
      proportion of men who accepted PNO services and the number of sexual partners
      informed by the PNO. RESULTS: There were 380 MSM diagnosed with syphilis. Those
      with primary or secondary syphilis reported a total of 813 partners over 3 months
      and those with early latent syphilis reported a total of 1400 partners over 12
      months. Sixty nine percent of index men (n = 262) had documented discussion of
      partner notification, 34% (n = 128) accepted PNO referral, and 28% (n = 105) were
      contacted by the PNO, 58 of whom reported they had already notified partners
      themselves. Only 14 index men (4%) provided the PNO with contact details for 28
      partners, 25 of whom were notified by the PNO. Among those interviewed, the most
      common barrier to partner notification was the presence of anonymous partners and
      absence of contact details for partners. CONCLUSIONS: Despite offering an
      effective PNO service in our centre, ultimately only 4% of MSM with syphilis had
      at least 1 partner notified by the PNO with patients declining the PNO service
      and anonymous partners posing the major barriers. Alternative patient initiated
      methods for improving partner notification for syphilis among MSM using newer
      communication technologies are required.

PMID- 27893598
TI  - Acceptability and Effectiveness of Assisted Human Immunodeficiency Virus Partner
      Services in Mozambique: Results From a Pilot Program in a Public, Urban Clinic.
AB  - BACKGROUND: Assisted partner services (APS) involves offering persons with human
      immunodeficiency virus (HIV) assistance notifying and testing their sex partners.
      Assisted partner services is rarely available in sub-Saharan Africa. We
      instituted a pilot APS program in Maputo, Mozambique. METHODS: Between June and
      September 2014, community health workers (CHWs) offered APS to persons with newly
      diagnosed HIV (index patients [IPs]). Community health workers interviewed IPs at
      baseline, 4 and 8 weeks. At baseline, CHWs counseled IPs to notify partners and
      encourage their HIV testing, but did not notify partners directly. At 4 weeks,
      CHWs notified partners directly. We compared 4- and 8-week outcomes to estimate
      the impact of APS on partner notification, HIV testing and HIV case finding.
      RESULTS: Community health workers offered 223 IPs APS, of whom 220 (99%)
      accepted; CHWs collected complete follow-up data on 206 persons; 79% were women,
      74% were married, and 50% named >1 sex partner. Index patients named 262 HIV
      negative partners at baseline. At 4 weeks, before APS, IPs had notified 193
      partners (74%), but only 82 (31%) had HIV tested; 43 (13%) tested HIV positive.
      Assisted partner services resulted in the notification of 22 additional partners,
      testing of 83 partners and 43 new HIV diagnoses. In relative terms, APS increased
      partner notification, testing, and HIV case finding by 13%, 101%, and 125%.
      Seventy-two (35%) of 206 IPs were in ongoing HIV serodiscordant partnerships.
      Only 2.5 IPs needed to receive APS to identify a previously undiagnosed HIV
      infected partner or an ongoing HIV serodiscordant partnership. Two (1%) IPs
      reported APS-related adverse events. CONCLUSIONS: Assisted partner services is
      acceptable to Mozambicans newly diagnosed with HIV, identifies large numbers of
      serodiscordant partnerships and persons with undiagnosed HIV, and poses a low
      risk of adverse events.

PMID- 27893599
TI  - How Underestimates of Need Contribute to Biased Conclusions.

PMID- 27893601
TI  - Reducing Missed Opportunities: Pairing Sexually Transmitted Infection Screening
      With Syringe Exchange Services.
AB  - About 17.5% of sexually active injection drug users recruited from a syringe
      exchange in Camden, NJ (n = 120) screened positive for chlamydia/gonorrhea. Among
      these cases, 40% were detected via extragenital screening. This pilot
      demonstrates that colocating sexually transmitted infection control with syringe
      exchange leads to sexually transmitted infection case finding.

PMID- 27893600
TI  - Prevalence and Correlates of Genital Infections Among Newly Diagnosed Human
      Immunodeficiency Virus-Infected Adults Entering Human Immunodeficiency Virus Care
      in Windhoek, Namibia.
AB  - BACKGROUND: Identifying and treating genital infections, including sexually
      transmitted infections (STI), among newly diagnosed human immunodeficiency virus
      (HIV)-infected individuals may benefit both public and individual health. We
      assessed prevalence of genital infections and their correlates among newly
      diagnosed HIV-infected individuals enrolling in HIV care services in Namibia.
      METHODS: Newly diagnosed HIV-infected adults entering HIV care at 2 health
      facilities in Windhoek, Namibia, were recruited from December 2012 to March 2014.
      Participants provided behavioral and clinical data including CD4+ T lymphocyte
      counts. Genital and blood specimens were tested for gonorrhea, Chlamydia,
      trichomoniasis, Mycoplasma genitalium, syphilis, bacterial vaginosis, and
      vulvovaginal candidiasis. RESULTS: Among 599 adults, 56% were women and 15%
      reported consistent use of condoms in the past 6 months. The most common
      infections were bacterial vaginosis (37.2%), trichomoniasis (34.6%) and Chlamydia
      (14.6%) in women and M. genitalium (11.4%) in men. Correlates for trichomoniasis
      included being female (adjusted relative risk, [aRR], 7.18; 95% confidence
      interval [CI], 4.07-12.65), higher education (aRR, 0.58; 95% CI, 0.38-0.89), and
      lower CD4 cell count (aRR, 1.61; 95% CI, 1.08-2.40). Being female (aRR, 2.39; 95%
      CI, 1.27-4.50), nonmarried (aRR, 2.30; (95% CI, 1.28-4.14), and having condomless
      sex (aRR, 2.72; 95% CI, 1.06-7.00) were independently associated with chlamydial
      infection. Across all infections, female (aRR, 2.31; 95% CI, 1.79-2.98),
      nonmarried participants (aRR, 1.29; 95% CI, 1.06-1.59), had higher risk to
      present with any STI, whereas pregnant women (aRR, 1.16, 95% CI 1.03-1.31) were
      at increased risk of any STI or reproductive tract infection.

PMID- 27893602
TI  - Human Immunodeficiency Virus-Infected Man With Acute Visual Impairment and
      Panuveitis Due to Syphilis Despite Initially Negative Rapid Plasma Reagin.

PMID- 27893603
TI  - Young Low-Risk Heterosexual Clients Prefer a Chlamydia Home Collection Test to a
      Sexually Transmitted Infection Clinic Visit in Amsterdam, the Netherlands, A
      Cross-Sectional Study.
AB  - BACKGROUND: Home-based self-collection of specimens for urogenital and anorectal
      chlamydia testing has been proven feasible and acceptable. We studied the
      efficiency of chlamydia home collection kits for young low-risk persons to
      optimize care at the Amsterdam sexually transmitted infection (STI) clinic.
      METHODS: Low-risk heterosexual persons under 25 years submitting an appointment
      request online were offered 3 different ways of chlamydia testing: (1) receiving
      a home collection kit, (2) coming to the clinic without, or (3) with sexual
      health counseling. The collection kit was sent to the client by surface mail and
      was used to self-collect a vaginal swab or urine sample (men). This sample was
      sent back to the laboratory for testing and the results could be retrieved
      online. Testing for gonorrhea, syphilis, and human immunodeficiency virus was
      indicated after testing chlamydia-positive. RESULTS: Between September 2012 until
      July 2013, from 1804 online requests, 1451 (80%) opted for the home collection
      kit, 321 (18%) preferred an appointment at the clinic without, and 32 (2%) with
      sexual health counseling. Of the requested home collection kits, 88% were
      returned. Chlamydia was diagnosed in 6.0% of the clients receiving a home
      collection kit, and none of the chlamydia-positive clients tested positive for
      other STI. CONCLUSIONS: Home collection is the preferred method for most young
      low-risk heterosexual clients who seek STI care. With a high compliance to
      collect and return the samples, home collection can be used as a tool to increase
      efficiency and dedicate STI clinic workers efforts to those at highest risk.

PMID- 27893606
TI  - Cochlear, brainstem, and psychophysical responses show spectrotemporal tradeoff
      in human auditory processing.
AB  - Auditory filter theory posits a tradeoff in time-frequency analysis: high
      temporal precision is achievable only at the expense of poorer frequency
      resolution and vice versa. Here, we examined the hierarchy of brain mechanisms of
      these spectrotemporal tradeoffs through a series of physiological and behavioral
      measures aimed to tap temporal and spectral acuity at different levels of the
      auditory neuroaxis (cochlea->brainstem->percept). Cochlear and behavioral
      frequency selectivity was measured by stimulus-frequency otoacoustic emissions
      (SFOAE) and psychophysical tuning curves; temporal acuity was measured
      physiologically and behaviorally by paired click recovery of auditory brainstem
      responses (ABRs) and gap detection thresholds (GDTs), respectively. Comparison of
      physiological and behavioral estimates of temporal acuity and frequency tuning
      showed high consistency between measurement domains with temporal thresholds of
      ~3-4 ms and filter tuning Q3~10 across brain and behavioral measures. Cochlear
      SFOAE estimates of tuning inversely predicted listeners' temporal acuity
      estimated from both brainstem ABRs and behavioral GDTs. The high predictive power
      of cochlear responses on temporal thresholds and similarity between time
      frequency tradeoffs measured at progressively higher levels of the processing
      hierarchy (brainstem, behavior) suggest that the temporal resolution of human
      hearing established in the cochlea might be inherited at progressively higher
      levels of the hearing pathway.

PMID- 27893605
TI  - Synergistic combinations of five single drugs from Centella asiatica for neuronal
      differentiation.
AB  - To identify alternatives of nerve growth factor, which could promote NF68 protein
      expression and contribute toward neuronal differentiation, five compounds namely:
      asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained
      from Centella asiatica, were examined for their neuronal differentiation effects
      on PC12 cells. C. asiatica has been applied as an effective herbal medicine for
      the treatment of various diseases, including depression. According to a
      statistical design of experiments, both single compound and compound combinations
      were evaluated. A further statistical analysis indicated quantitative
      interactions between these five single compounds and led to the identification of
      the optimal drug combinations. Asiatic acid and madecassic appeared to show
      profound synergistic effects on neurofilaments expression in vitro. The optimized
      drug combinations were significantly more potent than single drugs and further
      investigation suggested that the optimal drug combination could be an analogue of
      nerve growth factor and could represent a potential treatment for
      neurodegenerative diseases.

PMID- 27893604
TI  - Implementation of Preexposure Prophylaxis for Human Immunodeficiency Virus
      Prevention Among Men Who Have Sex With Men at a New England Sexually Transmitted
      Diseases Clinic.
AB  - BACKGROUND: Preexposure prophylaxis (PrEP) is efficacious in preventing human
      immunodeficiency virus (HIV) among men who have sex with men (MSM). We assessed
      PrEP uptake among MSM presenting for services at a sexually transmitted diseases
      (STD) clinic. METHODS: Men who have sex with men presenting to the Rhode Island
      STD Clinic between October 2013 and November 2014 were educated about, and
      offered, PrEP. We categorized PrEP engagement using an implementation cascade to
      describe gaps in uptake which described MSM who: (1) were educated about PrEP,
      (2) indicated interest, (3) successfully received follow-up contact, (4)
      scheduled an appointment, (5) attended an appointment, and (6) initiated PrEP
      (ie, received a prescription). Bivariate and multivariable logistic regression
      models were used to examine predictors of PrEP initiation. RESULTS: A total of
      234 MSM were educated about PrEP; of these, 56% expressed interest. Common
      reasons for lack of interest were low HIV risk perception (37%), wanting more
      time to consider (10%), concern about side effects (7%), and financial barriers
      (3%). Among those interested, 53% followed up. Of those, 51% scheduled an
      appointment. The most common reason patients did not schedule an appointment was
      low HIV risk perception (38%). Seventy-seven percent of those with an appointment
      attended the appointment; of those, 93% initiated PrEP. Patients with higher HIV
      risk perception (adjusted odds ratios, 2.17; 95% confidence interval, 1.29-3.64)
      and a history of sex with an HIV-positive partner (adjusted odds ratios, 7.08;
      95% confidence interval, 2.35-21.34) had significantly higher odds of initiating
      PrEP. CONCLUSIONS: Low HIV-risk perception was the most significant barrier to
      PrEP uptake among MSM attending a public STD clinic.

PMID- 27893607
TI  - Acupuncture does not protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      induced damage of dopaminergic neurons in a preclinical mouse model of
      Parkinson's disease.
AB  - Acupuncture treatment, a complementary and alternative medicine, is associated
      with a suggested neuroprotective effect in previous preclinical studies of
      Parkinson's disease (PD); however, results from human clinical trials have been
      mixed or unsuccessful. Recent systematic reviews of translational neuroprotective
      studies showed that the supposed efficacy is confounded by low methodological
      quality, particularly by a lack of randomization and concealed allocation. We
      sought to replicate previous experimental findings with a study design that
      mitigates the introduction of bias, including randomization, blinded outcome
      measures, sham acupuncture application, and allocation concealment by blinded
      neurotoxin administration. We performed 12 sessions of manual acupuncture at
      acupoint GB34 (yanglingquan) in mice that were administered the 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine neurotoxin for five consecutive days. In this animal
      model of PD, acupuncture treatment did not attenuate tyrosine hydroxylase
      immunoreactive neuronal death, depletion of striatal dopamine levels, or reduced
      striatal tyrosine hydroxylase expression. Our results indicate that acupuncture
      is not neuroprotective against nigrostriatal loss in a subacute 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine mouse model of PD.

PMID- 27893608
TI  - Ape1 protects against MPP+-induced neurotoxicity through ERK1/2 signaling in PC12
      cells.
AB  - Oxidative stress, induced by reactive oxygen species (ROS), is an apoptosis
      activator. Oxidative stress causes dopaminergic neuron loss and plays a pivotal
      role in the pathogenesis of Parkinson's disease (PD). A recent study showed that
      apurinic/apyrimidinic endonuclease 1 (Ape1) decreases cytotoxicity and promotes
      neuron survival under oxidative stress. Furthermore, it has been proven that Ape1
      is involved in the pathogenesis of PD. However, little is known about the
      contribution of Ape1 toward the development of PD. Thus, the present study was
      designed to define a critical pathway by which Ape1 mediates neurotoxicity in a
      model of PD. The results show that Ape1 was upregulated in MPP-treated PC12
      cells. Ape1 overexpression significantly increased cell viability and inhibited
      apoptosis compared with MPP treatment, whereas Ape1 knockdown showed the opposite
      effect. Ape1 overexpression markedly suppressed ROS levels, whereas Ape1
      knockdown significantly elevated ROS levels. Furthermore, Ape1 overexpression
      markedly upregulated the p-ERK1/2 protein expression level and inhibited ERK1/2
      signaling. The ERK1/2 inhibitor PD98059 significantly decreased cell viability
      and increased apoptosis and the ROS level compared with the Ape1 overexpression
      group. Taken together, these results suggest that Ape1 protects against neuron
      death by activating the ERK1/2 signaling pathway.

PMID- 27893609
TI  - Swimming exercise reduces preference for a high-fat diet by increasing insulin
      sensitivity in C57BL/6 mice.
AB  - The present study examined the effect of 4-week swimming training on the
      preference for a high-fat diet and insulin sensitivity in mice. C57BL/6 J mice
      were placed on either a low-fat diet or a choice diet (with both low-fat and high
      fat diets available) for 6 weeks. During this period, a group of mice on the free
      choice diet were randomly selected to receive a 4-week swimming exercise
      intervention. Mice that received the swimming exercise intervention showed a
      reduced preference for the high-fat diet as well as a slower rate of weight gain.
      Moreover, changes in insulin sensitivity, tyrosine hydroxylase expression in the
      ventral tegmental area-nucleus accumbens system, and the expression of IRS2,
      IRS2, and high-fat diet-induced Akt phosphorylation in the nucleus accumbens were
      delayed in the swimming exercise intervention group. Taken together, these
      results suggest that swimming exercise regulates the dopaminergic reward system
      to decrease high-fat diet intake, thereby controlling body weight to prevent
      obesity, in a manner likely mediated by increased insulin signal transduction in
      the nucleus accumbens.

PMID- 27893610
TI  - Slit2/Robo1 promotes synaptogenesis and functional recovery of spinal cord
      injury.
AB  - Neuronal network reconstruction is a pivotal determinant for functional recovery
      after spinal cord injury (SCI), the process of which includes synaptogenesis.
      Slit2 protein has been identified as a key regulator of axon regeneration and
      synapse formation in the vertebrate. Meanwhile, RhoA is the converging cascade of
      inhibitory molecules that interrupt synaptic plasticity in SCI. In the present
      study, we investigated the interaction among Slit2, Robo1, and RhoA and the
      potential roles of Slit2 in the pathological process of SCI. We showed that Slit2
      was decreased, whereas Robo1 and RhoA were increased in the same surviving
      neurons in the spinal cord following SCI. We also found that inhibition of Slit2
      led to upregulation of the expression of Robo1 and RhoA. However, the severe
      dysfunctions of the locomotor performance induced by SCI were reversed by
      treatments of Slit2-N, the active portion of Slit2, knockdown of Robo1 by the
      RNAi lentivirus, or inhibition of RhoA by the C3 exoenzyme, respectively. Further
      results suggested that downregulation of Slit2 and therefore upregulation of
      Robo1 and RhoA inhibited the activity of growth cone and hindered the formation
      of new synapses of surviving neurons near the injury sites of the spinal cord
      following SCI. Our study indicated a new mechanism of deficiency of
      synaptogenesis during the development of SCI and provided a potential strategy
      for the treatment of SCI.

PMID- 27893611
TI  - Absence of miR-182 Augments Cardiac Allograft Survival.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate
      the posttranscriptional expression of target genes and are important regulators
      in immune responses. Previous studies demonstrated that the miRNA, miR-182 was
      significantly increased during allograft rejection. Further, the transcription
      factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182.
      The aim of this study is to further examine the role of miR-182 in alloimmune
      responses. METHODS: Transplantation of BALB/c cardiac allografts was performed in
      C57BL/6, miR-182, B6.129S-H2 (MHC II and CD4 T cell-deficient) and B6.129S2-Tap1
      (MHC I and CD8 T cell-deficient) mice, with or without CTLA-4Ig administration. T
      cell phenotype, FOXO1 protein levels and graft infiltrating lymphocytes were
      determined in C57BL/6 or miR-182 mice by flow cytometric analysis, Western blot,
      and immunohistochemistry, respectively. RESULTS: We now show that T cells, mainly
      CD4 are the main cellular source of miR-182 during allograft rejection. In the
      absence of miR-182, CTLA-4Ig treatment significantly increased allograft survival
      (31.5 days C57BL/6 vs 60 days miR-182; P < 0.01). Further, CTLA4-Ig treatment
      inhibits miR-182 expression, increases FOXO1 levels, and reduces the percentage
      of CD4CD44 T cells after transplantation. Fewer T cells infiltrate the cardiac
      allografts, and memory T cells are significantly decreased in allograft
      recipients deficient in miR-182 with CTLA4-Ig treatment (P < 0.01). CONCLUSIONS:
      Our findings suggest that miR-182 contributes to the T-cell responses to
      alloantigen especially under costimulation blockade. Therapeutics that target
      specific miRNAs may prove beneficial in transplantation.

PMID- 27893612
TI  - The Influence of Timing and Frequency of Adipose-Derived Mesenchymal Stem Cell
      Therapy on Immunomodulation Outcomes After Vascularized Composite
      Allotransplantation.
AB  - BACKGROUND: Cellular therapies for immunomodulation in vascularized composite
      allotransplantation (VCA) have gained importance due to their potential for
      minimization of immunosuppression. Adipose-derived (AD) mesenchymal stem cells
      (MSCs) especially have shown encouraging potential. We investigated the influence
      of timing and frequency of AD-MSC treatment on immunologic and graft survival as
      well as graft vasculopathy outcomes after VCA. METHODS: Lewis rats received full
      mismatched Brown Norway rat hindlimb transplants. Recipient animals were assigned
      to groups receiving donor-derived AD-MSCs (10 cells/animal) either on
      postoperative day (POD) 1, POD 4, or repeatedly on POD 4, 8, and 15, and compared
      to untreated controls. RESULTS: Although AD-MSC administration on POD 1 or POD 4,
      8, and 15 resulted in 50% long-term graft acceptance, recipients treated on POD
      4, and controls rejected before POD 50. All treated animals revealed peripheral
      blood chimerism (4 weeks), most pronounced after repetitive cell administration
      (12.92% vs 5.03% [POD 1] vs 6.31% [POD 4]; P < 0.05; all P < 0.01 vs control
      1.45%). Chimerism was associated with the generation of regulatory T cells
      (CD4CD25FoxP3). In vitro mixed lymphocyte reactions revealed modulation of the
      recipient immune response after AD-MSC treatment. Graft arteries at end point
      revealed significant differences of arterial intimal thickness between rejecting
      and AD-MSC-treated animals (P < 0.01). CONCLUSIONS: Taken together, our results
      point to the potential for repetitive AD-MSC administration in improving outcomes
      after VCA. Future studies are warranted into optimization of the dosing and
      frequency of AD-MSC therapy, either alone or used in, combination with other cell
      therapies (such as hematopoietic stem cells or bone marrow-derived MSC or
      dendritic cells) for optimization of appropriate conditioning or maintenance
      regimens.

PMID- 27893615
TI  - Biomarkers for Cardiac Allograft Vasculopathy: Still Searching After All These
      Years.

PMID- 27893614
TI  - The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of
      Chronic Lung Allograft Dysfunction or CLAD-Related Death.
AB  - BACKGROUND: Development of donor-specific antibodies (DSA) after lung
      transplantation is associated with antibody mediated rejection, acute cellular
      rejection, and bronchiolitis obliterans syndrome; however, the significance of
      circulating antibodies before transplant remains unclear. METHODS: We performed a
      retrospective cohort study including recipients of primary lung transplants
      between 2008 and 2012. We assessed the impact of circulating HLA and noncytotoxic
      DSA detected before transplant on development of Chronic Lung Allograft
      Dysfunction (CLAD) or CLAD-related death. RESULTS: 30% of subjects had
      circulating class I antibodies alone, 4% Class II, and 14.4% class I and class II
      at mean fluorescent intensity greater than 1000. Nine percent of the subjects had
      DSA class I, 9% class II, and 2.4% both DSA classes 1 and 2. Neither the presence
      of circulating antibodies (adjusted hazard ratio, 0.87; 95% confidence interval,
      0.50-1.54) nor the presence of DSA (adjusted hazard ratio, 1.56; 95% confidence
      interval, 0.77-3.18) before transplant at mean fluorescent intensity greater than
      1000 was associated with the development of CLAD or CLAD-related death.
      CONCLUSIONS: Although in previous studies we have shown an increased incidence of
      antibody-mediated rejection in patients with pretransplant DSA, neither the
      presence of HLA antibodies nor DSA translated to an increased risk of allograft
      dysfunction or death if prospective crossmatch testing was negative. Prospective
      studies are needed to define the impact of pretransplant sensitization on lung
      transplant recipients.

PMID- 27893616
TI  - Immunological Risk Stratification by Assessing Both the HLA and Non-HLA-Specific
      Antibodies: Time to Include Testing for Non-HLA Antibodies in the Routine
      Clinical Antibody Analysis Profile?

PMID- 27893618
TI  - Early resuscitation with lyophilized plasma provides equal neuroprotection
      compared with fresh frozen plasma in a large animal survival model of traumatic
      brain injury and hemorrhagic shock.
AB  - BACKGROUND: Combined traumatic brain injury (TBI) and hemorrhagic shock (HS) is
      highly lethal. In previous models of combined TBI + HS, we showed that early
      resuscitation with fresh frozen plasma (FFP) improves neurologic outcomes.
      Delivering FFP, however, in austere environments is difficult. Lyophilized plasma
      (LP) is a logistically superior alternative to FFP, but data are limited
      regarding its efficacy for treatment of TBI. We conducted this study to determine
      the safety and long-term outcomes of early treatment with LP in a large animal
      model of TBI + HS. METHODS: Adult anesthetized swine underwent TBI and volume
      controlled hemorrhage (40% blood volume) concurrently. After 2 hours of shock,
      animals were randomized (n = 5 per /group) to FFP or LP (1* shed blood)
      treatment. Serial blood gases were drawn, and thromboelastography was performed
      on citrated, kaolin-activated whole-blood samples. Five hours after treatment,
      packed red blood cells were administered, and animals recovered. A 32-point
      Neurologic Severity Score was assessed daily for 30 days (0 = normal, 32 = most
      severe injury). Cognitive functions were tested by training animals to retrieve
      food from color-coded boxes. Brain lesion size was measured on serial magnetic
      resonance imaging, and an autopsy was performed at 30 days. RESULTS: The severity
      of shock and the degree of resuscitation were similar in both groups.
      Administration of FFP and LP was well tolerated with no differences in reversal
      of shock or thromboelastography parameters. Animals in both groups displayed the
      worst Neurologic Severity Score on postoperative Day 1 with rapid recovery and
      return to baseline within 7 days of injury. Lesion size on Day 3 in FFP-treated
      animals was 645 +/- 85 versus 219 +/- 20 mm in LP-treated animals (p < 0.05).
      There were no differences in cognitive functions or delayed treatment-related
      complications. CONCLUSIONS: Early treatment with LP in TBI + HS is safe and
      provides neuroprotection that is comparable to FFP.

PMID- 27893617
TI  - Differential Role of B Cells and IL-17 Versus IFN-gamma During Early and Late
      Rejection of Pig Islet Xenografts in Mice.
AB  - BACKGROUND: Xenogeneic islet transplantation is an emerging therapeutic option
      for diabetic patients. However, immunological tolerance to xenogeneic islets
      remains a challenge. METHODS: The current study used a pig-to-mouse discordant
      xenogeneic islet transplant model to examine antidonor xenogeneic immune
      responses during early and late rejection and to determine experimental
      therapeutic interventions that promote durable pig islet xenograft survival.
      RESULTS: We found that during early acute rejection of pig islet xenografts, the
      rejecting hosts exhibited a heavy graft infiltration with B220 B cells and a
      robust antipig antibody production. In addition, early donor-stimulated IL-17
      production, but not IFN-gamma production, dominated during early acute rejection.
      Recipient treatment with donor apoptotic 1-ethyl-3-(3'-dimethylaminopropyl)
      carbodiimide-treated splenocytes significantly inhibited antidonor IL-17
      response, and when combined with B cell depletion and a short course of rapamycin
      led to survival of pig islet xenografts beyond 100 days in approximately 65%
      recipients. Interestingly, treated recipients in this model experienced late
      rejection between 100 and 200 days posttransplant, which coincided with B cell
      reconstitution and an ensuing emergence of a robust antidonor IFN-gamma, but not
      IL-17, response. CONCLUSIONS: These findings reveal that early and late rejection
      of pig islet xenografts may be dominated by different immune responses and that
      maintenance of long-term xenogeneic tolerance will require strategies that target
      the temporal sequence of antixenogeneic immune responses.

PMID- 27893619
TI  - Substituting systolic blood pressure with shock index in the National Trauma
      Triage Protocol.
AB  - INTRODUCTION: The National Trauma Triage Protocol (NTTP) is an algorithm that
      guides emergency medical services providers through four decision steps to
      identify the patients that would benefit from trauma center care. The NTTP
      defines a systolic blood pressure (SBP) of less than 90 mm Hg as one of the
      criteria for trauma center need. The aim of our study was to determine the impact
      of substituting SBP of less than 90 mm Hg with shock index (SI) on triage
      performance. METHODS: A 2-year (2011-2012) retrospective analysis of all trauma
      patients 18 years or older in the National Trauma Databank was performed.
      Transferred patients, patients dead on arrival, and those with missing data were
      excluded. Our outcome measure was trauma center need defined by Injury Severity
      Score greater than 15, need for emergent operation, death in the emergency
      department, and intensive care unit stay of more than 1 day. Area under the
      characteristic curve and triage characteristics were compared between SBP of less
      than 90 mm Hg and SI of more than 1.0. Logistic regression analysis was performed
      to compare the mortality between patients triaged under current protocol of SBP
      of less than 90 mm Hg and patients triaged using the new defined protocol (SI
      >1.0). RESULTS: A total of 505,296 patients were included. Compared with SBP of
      less than 90 mm Hg, SI of more than 1.0 had a higher sensitivity (44.4% vs.
      41.7%) but lower specificity (80.2% vs. 82.4%). The area under the curve was
      significantly higher for SI of more than 1.0 (0.623 [95% confidence interval,
      0.622-.625] vs. 0.620 [95% confidence interval, 0.619-0.622]). Substituting SBP
      of less than 90 mm Hg with SI of more than 1.0 resulted in a decrease in
      undertriage rate of 30,233 patients (5.9%) but an increase in overtriage of only
      6,386 patients (1.3%). CONCLUSION: Substituting the current criterion of SBP of
      less than 90 mm Hg in the NTTP with an SI of more than 1.0 results in significant
      reduction in undertriage rate without causing large increase in overtriage.
      Because of simplicity of use, better discrimination power, and minimal effect on
      overtriage rates, future studies should consider exploring the possibility of
      replacing the current SBP of less than 90 mm Hg criterion with SI of more than
      1.0 in the NTTP. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic
      study, level IV.

PMID- 27893620
TI  - A Modified Iris Suture Technique for In-the-bag Intraocular Lens Dislocation.

PMID- 27893621
TI  - CHOROIDAL CHANGES ASSOCIATED WITH SEROUS MACULAR DETACHMENT IN EYES WITH
      STAPHYLOMA, DOME-SHAPED MACULA OR TILTED DISK SYNDROME.
AB  - PURPOSE: To study the relationship of choroidal abnormalities with serous retinal
      detachment (SRD) in eyes with staphyloma, dome-shaped macula, or tilted disk
      syndrome. METHODS: Group 1, 28 eyes of 20 patients with staphyloma/dome-shaped
      macula/tilted disk syndrome associated with SRD was compared with Group 2, 30
      eyes of 20 patients, with staphyloma/dome-shaped macula/tilted disk syndrome but
      without SRD. Radial and en-face optical coherence tomography and choroidal
      analysis were performed. RESULTS: Group 1 had a thicker mean subfoveal choroidal
      thickness (161 MUm vs. 92 MUm, P < 0.05) and a greater variation in choroidal
      thickness (112 MUm vs. 76 MUm, P > 0.05) compared with eyes of Group 2. Focal
      abrupt changes in choroidal thickness were more commonly seen in Group 1 versus
      eyes in Group 2 (90% vs. 30%, P < 0.05) and this area of abrupt change was
      located within or at the edge of the SRD in 64% of eyes. Large choroidal vessels
      (pachyvessels) (82% located within the area of SRD) were always associated with
      the presence of SRD. CONCLUSION: An abrupt transition in choroidal thickness may
      be involved in the pathogenesis of SRD. In some cases, a radial scan pattern may
      better demonstrate mild SRD, choroidal contours and the focal choroidal
      variations than horizontal or vertical raster scan patterns.

PMID- 27893622
TI  - IMAGE QUALITY AND ARTIFACTS ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY:
      Comparison of Pathologic and Paired Fellow Eyes in 65 Patients With Unilateral
      Choroidal Melanoma Treated With Plaque Radiotherapy.
AB  - PURPOSE: To study image quality and artifacts seen on optical coherence
      tomography angiography (OCTA). METHODS: Sixty-five consecutive patients with
      unilateral posterior uveal melanoma treated with plaque radiotherapy had OCTA
      during follow-up. Optical coherence tomography angiography was performed on both
      the affected and fellow eye. Signal strength and frequency of image artifacts on
      en face images were compared between affected and fellow eyes. RESULTS: A total
      of 130 eyes in 65 patients were analyzed, the mean age at time of OCTA was 55
      years (median: 56, range: 12-81 years), and 39 (39/65, 60%) were female. Majority
      of tumors were located in the choroid (62/65, 95%) and extramacular (55/65, 85%).
      The mean distance to the foveola was 4 mm (median: 3, range: 0-18 mm) and optic
      nerve was 4 mm (median: 4, range: 0-16 mm). Optical coherence tomography
      angiography was performed at a mean 46 months after plaque radiotherapy. Most
      patients had a history of radiation maculopathy or papillopathy in the treated
      eye at the time of OCTA (46/65, 71%). Overall, 95 eyes (95/130, 73%) had at least
      one significant artifact on OCTA. The most common major artifacts were loss of
      focus (71/130, 55%), broad (>5 pixels width and >4 lines) blink lines (48/130,
      37%), motion artifact (34/130, 26%), specular dot (33/130, 25%), and edge
      duplication (10/130, 8%). Statistically, eyes treated with plaque radiotherapy
      (affected vs. fellow eye) were more likely to have at least one major OCTA
      artifact (92 vs. 54%, P < 0.001) and, specifically, loss of focus was more
      frequent (78 vs. 31%, P < 0.001). Multivariate analysis found decreased visual
      acuity significantly associated with higher incidence of broad blink lines (P =
      0.0166) and loss of signal (P < 0.0001), whereas male sex was associated with
      increased loss of signal (P = 0.0015), and distance to the foveola was related to
      edge duplication (P = 0.0119). CONCLUSION: Image artifacts on OCTA are commonly
      encountered and appear to be more frequent in eyes with pathology and poor visual
      acuity. Recognition of these artifacts might help improve image interpretation
      and decision making.

PMID- 27893623
TI  - EFFICACY AND SAFETY OF INTRAVITREAL CONBERCEPT INJECTIONS IN MACULAR EDEMA
      SECONDARY TO RETINAL VEIN OCCLUSION.
AB  - PURPOSE: To assess the efficacy and safety of intravitreal conbercept injections
      in patients with macular edema secondary to retinal vein occlusion (RVO).
      METHODS: A prospective, Phase II clinical trial was performed on 60 patients with
      macular edema secondary to RVO. Thirty patients had branch RVO (BRVO) and 30 had
      central RVO (CRVO). Each patient received intravitreal injections of conbercept
      monthly up to 3 months, followed by monthly evaluation and injection pro re nata
      to Month 9. RESULTS: The average change of best-corrected visual acuity from
      baseline to Month 9 was 17.83 +/- 10.89 letters in BRVO and 14.23 +/- 11.74
      letters in CRVO. The change in best-corrected visual acuity was not statistically
      different between the groups (P = 0.216). The mean reduction of central retina
      thickness from baseline to Month 9 was 289.97 +/- 165.42 MUm and 420.47 +/-
      235.89 MUm in BRVO and CRVO, respectively. The mean numbers of injections was
      7.14 +/- 1.90 in BRVO and 7.59 +/- 1.39 in CRVO from baseline to Month 9 (P =
      0.4705). There were 7 serious adverse events (SAEs) in 5 patients (8.33%, 2 BRVO
      and 3 CRVO). All the SAEs were nonocular and were not related to the drug or the
      injection procedure. CONCLUSION: Intravitreal injections of conbercept
      demonstrated a generally favorable safety and tolerability profile as well as
      efficacy in the treatment of macular edema due to RVO.

PMID- 27893624
TI  - PROSPECTIVE EVALUATION OF A SUSTAINED-RELEASE DEXAMETHASONE INTRAVITREAL IMPLANT
      FOR CYSTOID MACULAR EDEMA IN QUIESCENT UVEITIS.
AB  - PURPOSE: To investigate dexamethasone intravitreal implant (DEX implant; OZURDEX,
      Allergan, Inc) in the treatment of uveitic cystoid macular edema that had
      persisted in the absence of intraocular inflammation. METHODS: In this
      prospective interventional case series, 10 patients with uveitic cystoid macular
      edema and quiescent uveitis were treated with dexamethasone intravitreal implant
      at baseline and evaluated monthly for one year. Patients were retreated whenever
      cystoid macular edema recurred. The primary outcome measure was best-corrected
      visual acuity (BCVA) at day 90. RESULTS: At day 90, mean improvement from
      baseline BCVA was 14.4 letters (P = 0.0003), 70% of patients had a >=10 letter
      BCVA improvement, 50% of patients had a >=15 letter BCVA improvement, and the
      mean decrease from baseline central subfield retinal thickness was 140 MUm (P =
      0.008). Improvements were maintained through day 360 with retreatment as needed.
      At day 360, mean improvement in BCVA was 16.5 letters (P = 0.006) and the mean
      decrease in central subfield retinal thickness was 158 MUm (P = 0.002). One
      patient experienced intraocular pressure >25 mmHg (managed with topical
      medication). Two phakic patients (2/8; 25%) had worsening of lens opacity
      requiring cataract extraction. CONCLUSION: Dexamethasone intravitreal implant may
      be an effective treatment for patients with persistent cystoid macular edema in
      quiescent uveitis.

PMID- 27893625
TI  - Robotic Vitreoretinal Surgery.
AB  - PURPOSE: To review the current literature on robotic assistance for ophthalmic
      surgery, especially vitreoretinal procedures. METHODS: MEDLINE, Embase, and Web
      of Science databases were searched from inception to August, 2016, for articles
      relevant to the review topic. Queries included combinations of the terms: robotic
      eye surgery, ophthalmology, and vitreoretinal. RESULTS: In ophthalmology, proof
      of-concept papers have shown the feasibility of performing many delicate anterior
      segment and vitreoretinal surgical procedures accurately with robotic assistance.
      Multiple surgical platforms have been designed and tested in animal eyes and
      phantom models. These platforms have the capability to measure forces generated
      and velocities of different surgical movements. "Smart" instruments have been
      designed to improve certain tasks such as membrane peeling and retinal vessel
      cannulations. CONCLUSION: Ophthalmic surgery, particularly vitreoretinal surgery,
      might have reached the limits of human physiologic performance. Robotic
      assistance can help overcome biologic limitations and improve our surgical
      performance. Clinical studies of robotic-assisted surgeries are needed to
      determine safety and feasibility of using this technology in patients.

PMID- 27893638
TI  - Arteriovenous fistula between the common femoral artery and vein secondary to
      transpelvic gunshot wound.

PMID- 27893639
TI  - Surgical rescue: The next pillar of acute care surgery.
AB  - BACKGROUND: The evolving field of acute care surgery (ACS) traditionally includes
      trauma, emergency general surgery, and critical care. However, the critical role
      of ACS in the rescue of patients with a surgical complication has not been
      explored. We here describe the role of "surgical rescue" in the practice of ACS.
      METHODS: A prospective, electronic medical record-based ACS registry spanning
      January 2013 to May 2014 at a large urban academic medical center was screened by
      ICD-9 codes for acute surgical complications of an operative or interventional
      procedure. Long-term outcomes were derived from the Social Security Death Index.
      RESULTS: Of 2,410 ACS patients, 320 (13%) required "surgical rescue": most
      commonly, from wound complications (32%), uncontrolled sepsis (19%), and acute
      obstruction (15%). The majority of complications (85%) were related to an
      operation; 15% were related to interventional procedures. The most common rescue
      interventions required were bowel resection (23%), wound debridement (18%), and
      source control of infection (17%); 63% of patients required operative
      intervention, and 22% required surgical critical care. Thirty-six percent of
      complications occurred in ACS primary patients ("local"), whereas 38% were
      referred from another surgical service ("institutional") and 26% referred from
      another institution ("regional"). Hospital length of stay was longer, and in
      hospital and 1-year mortalities were higher in rescue patients compared with
      those without a complication. Outcomes were equivalent between "local" and
      "institutional" patients, but hospital length of stay and discharge to home were
      significantly worse in "institutional" referrals. CONCLUSION: We here describe
      the distinct role of the acute care surgeon in the surgical management of
      complications; this is an additional pillar of ACS. In this vital role, the acute
      care surgeon provides crucial support to other providers as well as direct
      patient care in the "surgical rescue" of surgical and procedural complications.
      LEVEL OF EVIDENCE: Epidemiological study, level III; therapeutic/care management
      study, level IV.

PMID- 27893640
TI  - A position paper: The convergence of aging and injury and the need for a
      Geriatric Trauma Coalition (GeriTraC).

PMID- 27893642
TI  - Comparison of nonoperative and surgical management of renal trauma: Can we
      predict when nonoperative management fails?
AB  - BACKGROUND: Limited data exist on risk factors for the failure of nonoperative
      management of renal trauma. Our study objective was to determine the incidence,
      salvage procedure, and risk factors for failure of nonoperative management of
      renal trauma. METHODS: The National Trauma Data Bank research data sets for
      admission years 2010-2014 were queried for renal injury by Abbreviated Injury
      Score code. Patients were stratified by interventional therapy (renal procedure
      code <24 hours from admission) and nonoperative management (no surgical renal
      procedure <24 hours). Abbreviated Injury Score was converted to American
      Association for the Surgery of Trauma renal injury grade. Demographics, patient
      and injury characteristics were compared between groups using stratified
      analysis. Multivariable logistic regression models were used to determine
      variables that were associated with failure of nonoperative management. RESULTS:
      A review of 3,977,634 cases revealed 19,572 renal injuries that met study
      criteria. A total of 16.6% were managed with interventional therapy, and 83.4%
      were managed nonoperatively, of which 2.7% failed nonoperative management. Risk
      adjusted multivariate regression indicated that penetrating injury (stab: odds
      ratio [OR], 1.61; 95% confidence interval [CI], 1.02-2.53 [p = 0.040]; and
      gunshot wound: OR, 1.40; 95% CI, 1.04-1.90 [p = 0.029]), highest abdominal injury
      grade for nonrenal organs (OR, 2.06; 95% CI, 1.65-2.57), and highest renal injury
      grade (OR, 1.85; 95% CI, 1.54-2.21) were associated with failure of nonoperative
      management (all p < 0.001). Increasing injury grades were associated with
      increasing risk of failing nonoperative management (Grade III: OR, 1.94; 95% CI,
      1.35-2.90; Grade IV: OR, 9.79; 95% CI, 7.04-13.63; and Grade V: OR, 9.45; 95% CI,
      6.02-14.86 [all p < 0.001]). CONCLUSIONS: Nonoperative management in the first 24
      hours after fails in up to 2.7%. Renal injury grade, nonrenal abdominal injuries,
      and penetrating injuries predict for nonoperative management failure. Highest
      grade renal injuries are at increased risk of failure. LEVEL OF EVIDENCE:
      Prognostic/epidemiologic study, level III; therapeutic study, level IV.

PMID- 27893641
TI  - Routine surveillance cholangiography after percutaneous cholecystostomy delays
      drain removal and cholecystectomy.
AB  - INTRODUCTION: Percutaneous cholecystostomy (PC) is often performed for patients
      with acute cholecystitis who are at high risk for operative morbidity and
      mortality. However, the necessity for routine cholangiography after PC remains
      unclear. We hypothesized that routine surveillance cholangiography (RSC) after PC
      would provide no benefit compared to on-demand cholangiography (ODC) triggered by
      signs or symptoms of biliary pathology. METHODS: We performed a 3-year
      retrospective cohort analysis of patients managed with PC for acute cholecystitis
      at two tertiary care hospitals. Patients who had routine surveillance
      cholangiography (RSC, n = 43) were compared to patients who had on-demand
      cholangiography (ODC, n = 41) triggered by recurrent biliary disease. RESULTS:
      RSC and ODC groups were similar by severity of acute cholecystitis, presence of
      gallstones, systemic inflammatory response syndrome (SIRS) criteria at the time
      of PC, SIRS criteria 72 hours after PC, and hospital length of stay. Two patients
      in the ODC group developed clinical indications for cholangiography. All 44 RSC
      patients had cholangiography, and 67 total cholangiograms were performed in this
      group. Surveillance cholangiography identified six patients (14%) with cystic
      duct filling defect and seven patients (16%) with a common bile duct filling
      defect, all of whom were asymptomatic. Fifteen patients (35%) in the RSC group
      had 32 ERCP procedures; five patients (12%) in the ODC group had 7 ERCPs (p =
      0.021). The ODC group had fewer days to drain removal (35 vs. 61, p < 0.001) and
      days to cholecystectomy (39 vs. 81, p = 0.005). Rates of recurrent cholecystitis,
      cholangitis, gallstone pancreatitis, drain removal, and cholecystectomy were
      similar between groups. CONCLUSION: RSC after PC for acute cholecystitis
      identified biliary pathology in asymptomatic patients and propagated further
      testing, but did not provide clinical benefit. ODC was associated with earlier
      drain removal, earlier cholecystectomy, and decreased resource utilization. LEVEL
      OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.

PMID- 27893643
TI  - Early percutaneous dilational tracheostomy does not lead to an increased risk of
      surgical site infection following anterior spinal surgery.
AB  - BACKGROUND: Most patients with cervical spinal cord injuries require
      tracheostomy. The optimal timing is still a matter of debate. Previous studies
      showed that patients receiving early tracheostomy had fewer ventilator days and
      decreased rates of pneumonia and were mobilized earlier. Because of the proximity
      of the anterior approach to the tracheostoma, there is concern about an increased
      risk of surgical site infection (SSI) related to tracheostomy. METHODS: This was
      a retrospective analysis at a Level I trauma center of patient records from 2008
      to 2014, identifying all patients with spinal cord injury who received anterior
      cervical spinal surgery and had early percutaneous dilational tracheostomy (PDT).
      Follow-up for SSI was performed throughout hospital stay (mean, 110 days; median,
      96 days, with lower quartile 89 days and upper quartile 119 days) and at 6 weeks
      and 3 months (clinical examination and computed tomography scans). RESULTS: Fifty
      one patients underwent anterior spinal surgery with PDT performed within a median
      of 5 days (range, 1-18 days). Seventy-eight percent (n = 40) of patients had
      anterior spinal surgery, whereas 22% (n = 11) had a combined anterior-posterior
      repair. All percutaneous dilational tracheostomies were performed using the
      Ciaglia single-step dilation technique. Despite an SSI of one patient's
      cannulation site, no SSI of the anterior approach was observed. CONCLUSION:
      Performing a PDT in a timely fashion after anterior spinal surgery does not
      increase the risk of SSI. LEVEL OF EVIDENCE: Therapeutic study, level V.

PMID- 27893644
TI  - Western Trauma Association Critical Decisions in Trauma: Management of adult
      blunt splenic trauma-2016 updates.

PMID- 27893645
TI  - Preperitoneal pelvic packing reduces mortality in patients with life-threatening
      hemorrhage due to unstable pelvic fractures.
AB  - BACKGROUND: A 2015 American Association for the Surgery of Trauma trial reported
      a 32% mortality for pelvic fracture patients in shock. Angioembolization (AE) is
      the most common intervention; the Maryland group revealed time to AE averaged 5
      hours. The goal of this study was to evaluate the time to intervention and
      outcomes of an alternative approach for pelvic hemorrhage. We hypothesized that
      preperitoneal pelvic packing (PPP) results in a shorter time to intervention and
      lower mortality. METHODS: In 2004, we initiated a PPP protocol for pelvic
      fracture hemorrhage. RESULTS: During the 11-year study, 2,293 patients were
      admitted with pelvic fractures; 128 (6%) patients underwent PPP (mean age, 44 +/-
      2 years; Injury Severity Score (ISS), 48 +/- 1.2). The lowest emergency
      department systolic blood pressure was 74 mm Hg and highest heart rate was 120.
      Median time to operation was 44 minutes and 3 additional operations were
      performed in 109 (85%) patients. Median RBC transfusions before SICU admission
      compared with the 24 postoperative hours were 8 versus 3 units (p < 0.05). After
      PPP, 16 (13%) patients underwent AE with a documented arterial blush.Mortality in
      this high-risk group was 21%. Death was due to brain injury (9), multiple organ
      failure (4), pulmonary or cardiac failure (6), withdrawal of support (4), adverse
      physiology (3), and Mucor infection (1). Of those patients with physiologic
      exhaustion, 2 died in the operating room at 89 and 100 minutes after arrival,
      whereas 1 died 9 hours after arrival. CONCLUSIONS: PPP results in a shorter time
      to intervention and lower mortality compared with modern series using AE.
      Examining mortality, only 3 (2%) deaths were attributed to the immediate sequelae
      of bleeding with physiologic failure. With time to death under 100 minutes in 2
      patients, AE is unlikely to have been feasible. PPP should be used for pelvic
      fracture-related bleeding in the patient who remains unstable despite initial
      transfusion. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 27893647
TI  - Cervical spine MRI in patients with negative CT: A prospective, multicenter study
      of the Research Consortium of New England Centers for Trauma (ReCONECT).
AB  - BACKGROUND: Although cervical spine CT (CSCT) accurately detects bony injuries,
      it may not identify all soft tissue injuries. Although some clinicians rely
      exclusively on a negative CT to remove spine precautions in unevaluable patients
      or patients with cervicalgia, others use MRI for that purpose. The objective of
      this study was to determine the rates of abnormal MRI after a negative CSCT.
      METHODS: Blunt trauma patients who either were unevaluable or had persistent
      midline cervicalgia and underwent an MRI of the C-spine after a negative CSCT
      were enrolled prospectively in eight Level I and II New England trauma centers.
      Demographics, injury patterns, CT and MRI results, and any changes in cervical
      spine management as a result of MRI imaging were recorded. RESULTS: A total of
      767 patients had MRI because of cervicalgia (43.0%), inability to evaluate
      (44.1%), or both (9.4%). MRI was abnormal in 23.6% of all patients, including
      ligamentous injury (16.6%), soft tissue swelling (4.3%), vertebral disc injury
      (1.4%), and dural hematomas (1.3%). Rates of abnormal neurological signs or
      symptoms were not different among patients with normal versus abnormal MRI. (15.2
      vs. 18.8%, p = 0.25). The c-collar was removed in 88.1% of patients with normal
      MRI and 13.3% of patients with an abnormal MRI. No patient required halo
      placement, but 11 patients underwent cervical spine surgery after the MRI
      results. Six of the eleven had neurological signs or symptoms. CONCLUSIONS: In a
      select population of patients, MRI identified additional injuries in 23.6% of
      patients despite a normal CSCT. It is uncertain if this is a true limitation of
      CT technology or represents subtle injuries missed in the interpretation of the
      scan. The clinical significance of these abnormal MRI findings cannot be
      determined from this study group. LEVEL OF EVIDENCE: Therapeutic study, level IV.

PMID- 27893650
TI  - To the Editor.

PMID- 27893651
TI  - Response to Letter to the Editor.

PMID- 27893648
TI  - Quantity and Quality of Economic Evaluations in U.S. Nursing Research, 1997-2015:
      A Systematic Review.
AB  - BACKGROUND: The United States has a complex healthcare system that is undergoing
      substantial reformations. There is a need for high-quality, economic evaluations
      of nursing practice. An updated review of completed economic evaluations relevant
      to the field of nursing within the U.S. healthcare system is timely and needed.
      OBJECTIVES: The purpose of this study was to evaluate and describe the quantity
      and quality of economic evaluations in nursing-relevant research performed in the
      United States between 1997 and 2015. METHODS: Four databases were searched.
      Titles, abstracts, and full-text content were reviewed to identify studies that
      analyzed both costs and outcomes, relevant to nursing, performed in the United
      States, and used the quality-adjusted life year to measure effectiveness. For
      included studies, data were extracted from full-text articles using criteria from
      U.S. Public Health Service's Panel on Cost-Effectiveness in Health and Medicine.
      RESULTS: Twenty-eight studies met the inclusion criteria. Most (n = 25, 89%) were
      published in the last decade of the analysis, from 2006 to 2015. Assessment of
      quality, based on selected items from the panel guidelines, found that the
      evaluations did not consistently use the recommended societal perspective, use
      multiple resource utilization categories, use constant dollars, discount future
      costs and outcomes, use a lifetime horizon, or include an indication of
      uncertainty in results. The only resource utilization category consistently
      included across studies was healthcare resources. DISCUSSION: Only 28 nursing
      related studies meeting the inclusion criteria were identified as meeting robust
      health economic evaluation methodological criteria, and most did not include all
      important guideline items. Despite increases in absolute numbers of published
      studies over the past decade, economic evaluation has been underutilized in U.S.
      nursing-relevant research in the past two decades.

PMID- 27893653
TI  - Adjuvant radiotherapy for the treatment of stage IV rectal cancer after curative
      resection: A propensity score-matched analysis and meta-analysis.
AB  - The role of pelvic radiotherapy (RT) in stage IV rectal cancer with total
      mesorectal excision (TME) has not been defined. We evaluated the impact of RT on
      oncologic outcomes among patients with stage IV rectal cancer who underwent TME
      and performed a meta-analysis of published studies.The records of stage IV rectal
      cancer patients who underwent TME between August 2001 and December 2011 were
      reviewed. Patients who received pelvic RT (RT group) and those who did not (non
      RT group) were matched using a propensity score. Oncologic outcomes were compared
      between the groups. A systematic literature search and meta-analysis was
      conducted.One hundred seventy-six patients were matched with propensity score
      matching, resulting in 39 patients in each group. The local recurrence-free
      survival (LRFS) of the RT group was significantly higher than that of the non-RT
      group (2-year LRFS: 100% vs 83.6%, respectively, P = 0.038). The overall
      survival, disease-free survival, and systemic recurrence were not significantly
      different between the groups. In the meta-analysis, the RT group had a reduced
      risk for loco-regional recurrence than the non-RT group (RR: 0.48, 95% confidence
      interval: 0.29-0.79).Pelvic RT might have benefits for loco-regional control in
      patients with stage IV rectal cancer who undergo TME.

PMID- 27893652
TI  - Correlation between T2* (T2 star) relaxation time and cervical intervertebral
      disc degeneration: An observational study.
AB  - PURPOSE: To demonstrate the potential benefits of T2 relaxation time of
      intervertebral discs (IVDs) regarding the detection and grading of degenerative
      disc disease using 3.0-T magnetic resonance imaging (MRI) in a clinical setting.
      MATERIALS AND METHODS: Cervical sagittal T2-weighted, T2 relaxation MRI was
      performed at 3.0-T in 61 subjects, covering discs C2-3 to C6-7. All discs were
      morphologically assessed based on the Pfirrmann grade, and regions of interests
      (ROIs) were drawn over the T2 mapping. Receiver operating characteristic (ROC)
      analysis was performed among grades to determine the cut-off values. RESULTS:
      Cervical intervertebral discs (IVDs) of patients were commonly determined to be
      at Pfirrmann grades III to V. The nucleus pulposus (NP) values did not differ
      significantly between sexes at the same anatomic level (P > 0.05). In the NP, the
      T2 values tended to decrease with increasing grade (P < 0.000), and a significant
      difference was found in the T2 values between grades I to V (P < 0.05). T2 values
      based on disc degeneration level classification were as follows: grade I (>30
      milliseconds), grade II (24.55-29.99 milliseconds), grade III (21.65-24.54
      milliseconds), grade IV (18.35-21.64 milliseconds), and grade V (<18.34
      milliseconds). CONCLUSION: Our standardized method of region-specific
      quantitative T2 relaxation time evaluation seems capable of characterizing
      different degrees of disc degeneration quantitatively. The T2 values obtained in
      these cervical IVDs may serve as baseline values for future T2 measurements in
      both healthy and degenerated cervical discs.

PMID- 27893654
TI  - Safety comparison of four types of rabies vaccines in patients with WHO category
      II animal exposure: An observation based on different age groups.
AB  - To evaluate the safeties of 4 types of rabies vaccines for patients with WHO
      category II animal exposure, especially in different age groups.A total of 4000
      patients with WHO category II animal exposure were randomly divided into 4
      vaccine groups, and were respectively given with Vaccines A, B, C, and D. And
      subjects in each vaccine group were divided into 4 age groups (<=5, 5-18, 19-60,
      and >=60-year-old groups). Then adverse events (including local and systemic
      ones) were recorded and compared. Consequently, except for Vaccine B, patients
      under the age of 5 in Groups A, C, and D suffered from more adverse reactions
      than those in other age groups. Furthermore, for the children aged less than 5
      years, incidence of adverse events following administration of Vaccine B, with
      the dose of 0.5 mL and production of bioreactor systems, was significantly lower
      than Vaccines A and D.Our data showed that rabies vaccines with smaller doses and
      more advanced processing techniques are of relatively high safety for the
      patients, especially for the young children.

PMID- 27893655
TI  - A retrospective observational study of length of stay in hospital after
      colorectal cancer surgery in England (1998-2010).
AB  - The National Health Service (NHS) is facing financial constraints and thus there
      is considerable interest in ensuring the shortest but optimal hospital stays
      possible. The aim of this study was to investigate patterns of postoperative
      length of stay (LOS) stay across the English NHS and to identify factors that
      significantly influence both optimal and prolonged LOS.Data were obtained from
      the National Cancer Data Repository (NCDR). National patterns of LOS were
      examined and multilevel mixed effects logistic regression was used to study
      factors associated with an "ideal" (<=5 days) or a prolonged (>=21 days) LOS in
      hospital after major resection. Funnel plots were used to examine variation
      across hospitals in both risk-adjusted and unadjusted LOS.All 240,873 individuals
      who underwent major resection for colorectal cancer were diagnosed between 1998
      and 2010 in the English NHS. The overall median LOS was 10 (interquartile range
      [IQR] 7-14 days) days, but it fell over time from 11 (IQR 9-15) days in 1998 to 7
      (IQR 5-12) days in 2010. The proportion of people experiencing "ideal" LOS
      increased dramatically from 4.9% in 1998 to 34.2% in 2010, but the decrease in
      the proportion of patients who experienced a prolonged LOS was less marked
      falling from 11.2% to 8.4%, respectively. Control charts showed that there was
      significant variation in short and prolonged LOS across NHS trusts even after
      adjustment for case-mix.Significant variation in LOS existed between NHS
      hospitals in England throughout period 1998 to 2010. Understanding the underlying
      causes of this variation between surgical providers will make it possible to
      identify and spread best practice, improve services, and ultimately reduce LOS
      following colorectal cancer surgery.

PMID- 27893656
TI  - Is it feasible to detect epidermal growth factor receptor mutations in
      circulating tumor cells in nonsmall cell lung cancer?: A meta-analysis.
AB  - BACKGROUND: The value of circulating tumor cells (CTCs) in detecting epidermal
      growth factor receptor (EGFR) mutations in patients with nonsmall cell lung
      cancer (NSCLC) is controversial. We performed a meta-analysis to investigate the
      diagnostic significance of CTCs with tumor tissues as the standard control.
      METHODS: A systematic literature search, including papers published until
      November 26, 2015, was performed using PubMed, Medline, Embase, Web of Science,
      and the China National Knowledge Infrastructure, and the references of retrieved
      articles were screened. The pooled sensitivity, specificity, and diagnostic odds
      ratio (DOR) were calculated according to the data selection from the included
      studies. The evaluation indexes of the diagnostic performance were the summary
      receiver operating characteristic curve (SROC) and area under the SROC (AUSROC).
      RESULTS: Eight eligible articles with a total of 170 participants were identified
      in our meta-analysis. The pooled sensitivity and specificity were 0.91 [95% CI:
      0.55-0.99] and 0.99 [95% CI: 0.59-1.00]. The positive likelihood ratio and
      negative likelihood ratio were 68 [95% CI: 1.4-3364] and 0.09 [95% CI: 0.01
      0.64], respectively. The DOR was 788 [95% CI: 9-71884]. The high diagnostic
      performance of CTCs in detecting EGFR mutations was indicated by the AUSROC of
      0.99 [95% CI: 0.98-1.00]. CONCLUSIONS: CTCs are a feasible and highly specific
      biomarker for detecting the EGFR mutation status in NSCLC patients.

PMID- 27893658
TI  - Freeze-all embryo transfer awareness and acceptance of IVF-ET patients in China.
AB  - The aim of the study was to determine the level of awareness and acceptance of in
      vitro fertilization pre-embryo transfer (IVF-ET) patients for freeze-all embryo
      transfer, improve relevant technical specifications, and optimize treatment
      results based on medical experience.Questionnaires were completed by women who
      received in vitro fertilization embryo transfer. A total of 377 valid samples
      were included into this study. Through focus group discussions and tablet
      assisted intercept interviews, we analyzed the basic situation, the awareness for
      frozen-all embryo transfer, and the need for frozen-all embryo transfer
      information for infertile patients.In this study, 60% of patients received IVF-ET
      for the first time, whereas the remaining patients received IVF-ET more than
      once. We investigated the current awareness and acceptance of IVF-ET patients for
      freeze-all embryo transfer quantificationally. Patients were grouped based on
      quantitative measurements, and the mainstream group of patients (72.7%) was
      precisely the patients who were worried and concerned of frozen-all embryo
      transfers. Although few of them could "rationally accept the comparative
      advantage of the technology," this group was vulnerable to doctors' guidance and
      education. Eventually, this group of patients accepted the frozen-all embryo
      transfer.Since there are no certain criteria for the kind of embryo transfer
      patients and reproductive centers should take, the choice should be taken
      individually according to the social economic situation and acceptance of
      patients for the frozen embryo transfer, as well as the technology of the
      reproductive center.

PMID- 27893657
TI  - Status of serum magnesium in Egyptian children with type 1 diabetes and its
      correlation to glycemic control and lipid profile.
AB  - Diabetes mellitus has been suggested to be the most common metabolic disorder
      associated with magnesium deficiency, having 25% to 39% prevalence. This deficit
      could be associated with the development of late diabetic complications,
      especially macroangiopathy.We aimed to evaluate the status of serum Mg in
      children with type 1 diabetes and assess its relation to glycemic control and
      lipid profile.We included 71 Egyptian children with type 1diabetes having their
      follow-up at Pediatric Endocrinology outpatient clinic, Zagazig University
      Hospital and 71 age- and sex-matched control. We measured Serum magnesium, HbA1c,
      and lipid profile in all study subjects.Diabetic children had significantly lower
      serum magnesium level compared to control children (1.83 +/- .27 mg/dL in
      diabetic children versus 2.00 +/- .16 mg/dL in control children). Taking cut-off
      level of serum magnesium <1.7 mg/dL for definition of hypomagnesemia,
      hypomagnesemia was detected in 28.2% of diabetic children compared to 9.9% of
      control children. In diabetic patients, there was statistically significant
      difference in HbA1c between hypomagnesemic and normomagnesemic group being higher
      in the low magnesium group, as it is mean +/- SD was 11.93 +/- 3.17 mg/dL in
      group I versus 8.92 +/- 0.93 mg/dL in the normomagnesemic group. Serum magnesium
      was found to be positively correlated with HDL (P < 0.001), and negatively
      correlated with age, HbA1c, triglycerides, total cholesterol, LDL, and duration
      of diabetes (P < 0.001).We concluded that total serum magnesium was frequently
      low in Egyptian children with type 1 diabetes and it is correlated with HbA1c and
      with lipid profile. Hypomagnesemia was more evident in patients with poor
      diabetic control and those with higher atherogenic lipid parameters. We suggest
      that low serum magnesium may be included in pathogenesis of poor glycemic control
      and abnormal lipid profile in children with type 1 diabetes. We need to perform
      further studies on giving magnesium supplements in diabetic children with
      hypomagnesemia to observe the effect of correction of serum magnesium on glycemic
      control, lipid profile, and the risk of diabetic complications.

PMID- 27893659
TI  - Serum CA125 concentration as a predictor of peritoneal dissemination of
      colorectal cancer in men and women.
AB  - Peritoneal dissemination (PD) of cancer is difficult to diagnose. Previous
      reports have shown that carbohydrate antigen 125 (CA125) is a sensitive marker of
      PD of gastric cancer. However, CA125 has not been evaluated as a marker of
      colorectal cancer (CRC), and its accuracy in men is controversial. The aim of
      this study was to compare the ability of CA125 and carcinoembryonic antigen (CEA)
      to predict PD of CRC in men and women.Preoperative CA125 and CEA concentrations
      were measured in 853 people (510 men, 343 women) over 10 years. PD was confirmed
      intraoperatively in 57 patients. The predictive ability was compared between
      CA125 and CEA.Compared with CEA, CA125 concentration had a lower sensitivity,
      higher specificity, and diagnostic accuracy, and significantly greater area under
      the curve. Further analysis of CA125's sensitivity and specificity among CEA
      negative group (n = 514) showed acceptable sensitivity (57.1%) and good
      specificity (92.0%). In men and women, CA125 concentration did not increase with
      stage from I to IV unless PD was present (P < 0.001). CEA concentration was
      increased in women with metastasis with PD (P < 0.001) or without PD (P < 0.001),
      but was increased only in men with metastasis without PD (P < 0.01). CA125
      concentration correlated with PD grade for men and women, but CEA concentration
      correlated with grade only in women.When analyzed according to the primary tumor
      site, CA125 concentration in men did not differ between patients with the primary
      site in the right or left colon, or the rectum, regardless of PD status. By
      contrast, CA125 concentration differed between PD-positive and PD-negative
      patients with cancer in the right (P < 0.001) or left (P < 0.001) colon but not
      in the rectum. CEA concentration in men did not differ according to the primary
      site or PD status. In women, CA125 and CEA concentrations differed significantly
      between the PD-positive and PD-negative groups in patients with the primary tumor
      in the right (P < 0.001) or left (P < 0.001) colon; tumor sites did not differ
      between the PD-positive and PD-negative groups.These findings suggest that CA125
      is a better tumor marker than CEA for predicting PD of CRC in both men and women.

PMID- 27893660
TI  - Salivary lactate dehydrogenase and aminotransferases in diabetic patients.
AB  - Diabetes mellitus (DM) is a group of metabolic diseases resulting from impaired
      insulin secretion and/or action. DM is characterized by hyperglycemia that can
      lead to the dysfunction or damage of organs, including the salivary glands.The
      aim of this study was to compare the levels of salivary lactate dehydrogenase
      (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in
      diabetic patients.The study was approved by the Bioethics Committee of Wroclaw
      Medical University (Poland). The study comprised 90 adults of both sexes, aged 21
      to 57 years. The patients were divided into 3 groups: type 1 diabetics (D1), type
      2 diabetics (D2), and a healthy control group (C). Each group consisted of 30 age
      and sex-matched subjects. Total protein (P, by Lowry method), LDH, AST, ALT
      (with Alpha Diagnostics kits), and salivary flow rate were measured in
      unstimulated mixed saliva. The level of glycosylated hemoglobin (HbA1c) was
      measured with DCA 2000 Reagent Kit. The obtained data were analyzed using the
      Mann-Whitney U test and the Spearman rank at a significance level of P < 0.05
      with the use of STATISTICA 9.0 software.In comparison with C, D1 presented a
      significantly higher activity of LDH (P < 0.001), AST (P < 0.001), and ALT (P <
      0.01), whereas D2 indicated higher levels of LDH (P < 0.001) and ALT (P < 0.05)
      compared with C. Comparing D1 to D2, approximately 3-fold higher activity of AST
      (P < 0.01) and approximately 4.5-fold higher activity of ALT (P < 0.01) was
      observed.Higher levels of salivary LDH, AST, and ALT in D1 compared with D2 and C
      confirm that salivary glands of D1 might be attributed to autoimmunological
      damage associated with the pathomechanism of DM.

PMID- 27893661
TI  - Acute coronary vasospasm in a patient with eosinophilic granulomatosis with
      polyangiitis following NSAID administration: A case report.
AB  - Eosinophilic with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome)
      is a rare systemic disease characterized by a small-vessel necrotizing
      vasculitis. Cardiac manifestations are broad-ranging and are associated with a
      poor prognosis. Coronary vasospasm is uncommon.Here, we report a case of an acute
      coronary vasospasm in a patient with EGPA after corticosteroids withdrawal and
      nonsteroidal antiinflammatory drug (NSAID) introduction. This patient was
      initially misdiagnosed as bradykinin-mediated angioedema. A 30-year-old man
      presented with recurrence of abdominal pain and acute dyspnea. NSAID
      administration for pain during a flare was followed by coronary vasospasms
      leading to cardiac arrest. Corticosteroid treatment was recently interrupted by
      the patient.This case reports a rare cardiac complication of EGPA. NSAID might
      contribute to coronary vasospasm by eosinophilic degranulation in EGPA. Moreover,
      corticosteroid compliance must be emphasized among patients who display EGPA with
      high cardiac risk to prevent fatal issues.

PMID- 27893662
TI  - The transcriptomic G1-G6 signature of hepatocellular carcinoma in an Asian
      population: Association of G3 with microvascular invasion.
AB  - In this study, a transcriptomic group classification based on a European
      population is tested on a Singapore cohort. The results highlight the
      genotype/phenotype correlation in a Southeast Asian population. The G1-G6
      transcriptomic classification derived from hepatocellular carcinoma (HCC)
      resected from European patients, robustly reflected group-specific
      clinical/pathological features. We investigated the application of this molecular
      classification in Southeast Asian HCC patients.Gene expression analysis was
      carried out on HCC surgically resected in Singapore patients who were grouped
      into G1-G6 transcriptomic categories according to expression of 16 predictor
      genes (illustrated in Supplementary Table 1, http://links.lww.com/MD/B413 and
      Supplementary Fig. 1, http://links.lww.com/MD/B413) using quantitative reverse
      transcription polymerase chain reaction (RT-PCR). Univariate and multivariate
      polytomous logistic regression was used to investigate association between
      clinical variables and pooled transcriptomic classes G12, G3, and G456.HCC from
      Singapore (n = 82) were distributed (%) into G1 (13.4), G2 (24.4), G3 (15.9), G4
      (24.4), G5 (14.6), and G6 (7.3) subgroups. Compared to the European data, the
      Singapore samples were relatively enriched in G1-G3 versus G4-G6 tumors (53.7% vs
      46.3%) reflecting the higher proportion of hepatitis B virus (HBV) patients in
      Singapore versus Europe samples (43% vs 30%). Pooled classes were defined as G12,
      G3, and G456. G12 was associated with higher alpha-fetoprotein (AFP)
      concentrations (OR = 1.69, 95% CI: 1.30-2.20; P < 0.0001) and G3 with
      microvascular invasion (OR = 4.91, 95% CI: 1.06-24.8; P = 0.047).The European and
      Singapore cohorts were generally similar relative to associations between
      transcriptomic groups and clinical features. This lends credence to the G1-G6
      transcriptomic classifications being applicable regardless of the ethnic origin
      of HCC patients. The G3 group was associated with microvascular invasion and
      holds potential for investigation into the underlying mechanisms and selection
      for therapeutic clinical trials.

PMID- 27893663
TI  - Revision surgery for curve progression after implant removal following posterior
      fusion only at a young age in the treatment of congenital scoliosis: A case
      report.
AB  - RATIONALE: Congenital scoliosis due to a hemivertebra creates a wedge-shaped
      deformity, which progresses and causes severe spinal deformities as an individual
      grows. The treatment of congenital scoliosis focuses on early diagnosis and
      appropriate surgical management before the development of severe deformity.
      PATIENT CONCERNS: We report the case of a 4-year-old male child with a left
      thoracolumbar scoliosis of 27 degrees  (T10-T12) due to a T11 hemivertebra who
      was treated by posterior fusion and pedicle screw fixation at the age of 4 years.
      The implant was removed due to pain secondary to implant prominence after 4 years
      without definitive revision surgery, which led to significant progression of the
      scoliosis, to 50 degrees . The indication for posterior vertebral column
      resection (PVCR) is a congenital spinal deformity with a curve magnitude greater
      than 30 degrees  with fast progression. This includes documented progression of
      the curve by more than 5 degrees  in a 6- month period, failure of conservative
      treatment, or both. OUTCOMES: The patient underwent PVCR of the T11 hemivertebra.
      Nine years after the revision surgery with PVCR, the patient showed satisfactory
      results and his spine was well balanced. LESSONS: This case shows that removal of
      an implant that was not the only cause of curve progression at a young age may
      lead to progression of scoliosis and, therefore, should be avoided unless it is
      absolutely necessary. CONCLUSION: Congenital scoliosis due to a hemivertebra at a
      young age could be treated by hemivertebra resection or anterior and posterior
      epiphysiodesis as definitive surgical treatment. The patient was eventually
      treated with PVCR, which achieved satisfactory correction without curve
      progression in a long-term follow-up.

PMID- 27893664
TI  - Genetic aspects of pituitary carcinoma: A systematic review.
AB  - BACKGROUND: Pituitary carcinoma (PC) is a rare type of malignant intracranial
      neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC
      incidence is low because only 0.1% to 0.2% of PAs ultimately develop into PCs,
      the prognosis is poor and 66% of patients die within the first year. Existing
      therapeutic measures, including surgical removal, chemotherapy, and radiotherapy,
      have limited effectiveness. The lack of efficacy of current treatments is largely
      caused by the limited understanding of the molecular pathogenesis of PA and the
      malignant transformation to PC. Therefore, the aim of this systematic review was
      to summarize published research regarding gene and protein expression in PC to
      clarify the molecular mechanisms underlying PC genesis and development and
      identify new candidate diagnostic biomarkers and therapeutic targets for
      potential use in personalized treatment of PC. METHODS: We followed the PRISMA
      guidelines to plan and conduct this systematic review. PubMed, Embase, and Web of
      Science databases were searched for relevant studies conducted before December
      16, 2015 describing the association of PC with gene expression at the mRNA and
      protein levels. MeSH terms combined with free terms were used to retrieve the
      references. RESULTS: In total, 207 records were obtained by primary search, and
      32 were included in the systematic review. Compared with normal pituitary gland
      and/or PA, 30 and 18 genes were found to have higher or lower expression,
      respectively, in PCs using different analytical methods. Among them, we selected
      9 upregulated and 7 downregulated genes for further analysis based on their
      identification as candidate treatment targets in other cancers, potential
      clinical application, or further research value. CONCLUSION: Previous studies
      demonstrated that many genes promote PC malignant transformation, angiogenesis,
      invasion, metastasis, and recurrence. Although most of these genes and proteins
      have not been fully analyzed with regard to their downstream mechanisms or
      potential diagnostic and therapeutic application, they have the potential to
      become candidate PC biomarkers and/or molecular targets for guiding personalized
      treatment. Modern advanced technologies should be utilized in future research to
      identify more candidate genes for PC pathogenesis, as precisely targeted gene
      therapies against PC are urgently required.

PMID- 27893666
TI  - Four weeks of paritaprevir/ritonavir/ombitasvir plus dasabuvir encountering
      dengue fever resulted in sustained virological response in an HCV patient: A case
      report.
AB  - BACKGROUND: Direct antiviral agent (DAA) has been the standard of care for
      patients with hepatitis C virus (HCV) infection. Twelve weeks of
      paritaprevir/ritonavir/ombitasvir plus dasabuvir (PROD) with or without ribavirin
      has shown to have a sustained virological response at post-treatment 12 weeks
      (SVR12) rate of >90% in HCV genotype 1 (HCV-1) patients. METHODS: We report a HCV
      1b patient who received only 25 days of PROD treatment. RESULTS: The patient
      early terminated treatment due to dengue fever but eventually achieved SVR12. It
      may attribute to low baseline viral loads and extraordinarily rapid suppression
      of HCV after treatment day1. CONCLUSIONS: The finding may shed light for possible
      response-guided-therapy for so-called ultra-super-responders in the DAA era.
      Whether the dengue virus, the Flaviviridae family as with HCV, enhanced the HCV
      clearance remains unclear and needs further exploration.

PMID- 27893665
TI  - Is it relevant to screen young women hospitalized in psychiatric department for
      neuropsychiatric systemic lupus erythematosus (NPSLE)?: A prospective study of
      100 psychiatric inpatients.
AB  - On the basis that diagnosis of neuropsychiatric systemic lupus erythematosus
      (NPSLE) is sometimes difficult and systemic lupus erythematosus (SLE) can present
      with isolated psychiatric symptoms, we initiated a survey in a psychiatric
      department to screen for NPSLE in young female inpatients.We prospectively
      studied consecutive young female patients referred to the department of
      psychiatry. Antinuclear antibodies (ANA), anti-deoxyribonucleic acid (DNA), and
      antiextractable soluble nuclear antigens (ENA) in the serum of patients were
      screened. In case of positive anti-DNA or anti-ENA, the patient was referred to
      the department of internal medicine.One hundred patients were enrolled, mean age
      33.1 +/- 8.4 years. Most patients presented underlying psychiatric disorders:
      depression (46%), schizophrenia (13%), anxiety disorder (6%), and personality
      disorder (10%). A quarter of the cohort did not display underlying psychiatric
      disorders before hospitalization. Positive ANA >=1:160 were found in 32 of the
      100 patients tested (32%). No patients presented anti-DNA antibodies. One patient
      had positive anti-sjogren's syndrome related antigen A (SSA), but did not present
      any features of SLE or Sjogren syndrome.Thus, systematic screening of SLE is not
      relevant in young women hospitalized in psychiatric department. However,
      clinicians should keep in mind that SLE can present with pure psychiatric
      symptoms.

PMID- 27893667
TI  - Abdominal compartment syndrome after endovascular repair for ruptured abdominal
      aortic aneurysm leads to acute intestinal necrosis: Case report.
AB  - INTRODUCTION: Abdominal compartment syndrome (ACS) after endovascular repair
      (EVAR) of rupture abdominal aortic aneurysm (rAAA) is a rare emergency situation,
      which has a high mortality. However, the progression of ACS is rapid and the
      diagnosis is usually been delayed, which increase the difficulties in treatment
      and affect the prognosis. We describe a case of a sever complication (acute
      intestinal necrosis) resulting from ACS after endovascular repair of rAAA.
      CLINICAL FINDING: An elderly man, 81 years old, complained a sudden lower
      abdominal and back pain without any predisposing cause. He had a history of
      hypertension for 20 years without any regular anti-hypertensive therapy. Physical
      Examination revealed that the blood pressure was 89/54 mmHg, pulse was 120/min,
      oxygen saturation was 91%. The abdominal ultrasound and the CTA (computed
      tomography angiography) scan revealed a rAAA. Emergency EVAR under general
      anesthesia was performed for this patient. DIAGNOSIS: Fourteen hours after
      endovascular repair, sudden decreased of blood pressure (70/50 mmHg) and oxygen
      saturation (70%) was observed. ACS or bleeding of retroperitoneal space was
      diagnosed. INTERVENTIONS: Abdominal laparotomy was immediately performed. ACS was
      verified and a severe complication (acute intestinal necrosis) was observed,
      intestinal resection was performed for this patient. OUTCOMES: Unfortunately,
      this patient died after operation because of multi-organ failure in a very short
      period, which is very rare regarding to this condition. Surgical pathology,
      diagnosis and management were discussed. CONCLUSION: ACS was occurred with a
      severe complication (acute intestinal necrosis) in a very short period, which is
      very rare regarding to this condition after EVAR, it reminds us the severe result
      of ACS and more methods to prevent it happened after surgical management.

PMID- 27893668
TI  - Outcome of endoscopy-negative iron deficiency anemia in patients above 65: A
      longitudinal multicenter cohort.
AB  - After the age of 65 years, iron deficiency anemia (IDA) requires the elimination
      of digestive neoplasia and is explored with upper and lower gastrointestinal (GI)
      endoscopy. However, such explorations are negative in 14% to 37% of patients. To
      further evaluate this issue, we evaluated the outcomes of patients aged over 65
      years with endoscopy-negative IDA.We retrospectively analyzed the outcomes of in
      patients over the age of 65 years with IDA (hemoglobin <12 g/dL and ferritin <70
      MUg/L) who had negative complete upper and lower GI endoscopies in 7 tertiary
      medical hospitals. Death, the persistence of anemia, further investigations, and
      the final diagnosis for IDA were analyzed after at least 12 months by calling the
      patients' general practitioners and using hospital records.Between 2004 and 2011,
      69 patients (74% women) with a median age of 78 (interquartile range (IQR) 75-82)
      years and hemoglobin and ferritin levels of 8.4 (IQR 6.8-9.9) g/dL and 14 (IQR 8
      27) MUg/L, respectively, had endoscopy-negative IDA, and 73% of these patients
      received daily antithrombotics. After a follow-up of 41 +/- 22 months, 23 (33%)
      of the patients were dead; 5 deaths were linked with the IDA, and 45 (65%)
      patients had persistent anemia, which was significantly associated with death (P
      = 0.007). Further investigations were performed in 45 patients; 64% of the second
      look GI endoscopies led to significant changes in treatment compared with 25% for
      the capsule endoscopies. Conventional diagnoses of IDA were ultimately
      established for 19 (27%) patients and included 3 cancer patients. Among the 50
      other patients, 40 (58%) had antithrombotics.In endoscopy-negative IDA over the
      age of 65 years, further investigations should be reserved for patients with
      persistent anemia, and second-look GI endoscopy should be favored. If the results
      of these investigations are negative, the role of antithrombotics should be
      considered.

PMID- 27893669
TI  - Cost of glaucoma treatment in a developing country over a 5-year period.
AB  - The aim of the study was to disclose a realistic estimate of primary open-angle
      glaucoma treatment, follow-up costs, and patients' monthly glaucoma-economic
      burden in an ophthalmology hospital in Mexico City.Prospective survey of 462
      primary open-angle glaucoma patients from 2007 to 2012 was carried out. Costs
      from visits, glaucoma follow-up studies, laser, and glaucoma surgical procedures
      were obtained from hospital pricings. Education, employment, and monthly income
      were interrogated. Total cost was divided into hypotensive treatment cost,
      nonpharmacologic treatment cost (laser and surgeries), and follow-up studies and
      consults. Average wholesale price for drugs analyzed was obtained from IMS Health
      data; monthly cost was calculated using: Monthly cost  = ([average wholesale
      price/number of drops per eye dropper] * number of daily applications) * 30
      days.Patients were classified according to their glaucoma severity, and data were
      analyzed based on monthly income (average annual exchange rate: 12.85 Mexican
      pesos = 1 USD).The mean age was 70 +/- 10 years, women = 81%, elementary school =
      39%, and unemployed = 53%. Low-income group = 266 patients (57%), 146 with mild
      glaucoma; moderate-income group = 176 patients (38%), 81 with mild glaucoma; high
      income group = 20 patients (4.3%), 10 with mild glaucoma. Patients' monthly
      average economic burden in glaucoma treatment: low-income patients = 61.5%,
      moderate-income patients = 19.5%, and high-income patients = 7.9%.Glaucoma
      economic burden is substantial not only for health systems, but for the family
      and the patient. Therefore, screening plans for earlier diagnosis, and health
      policies that lessen the cost of disease management and increase adherence to
      treatment, and reduce the prevalence of blindness attributed to glaucoma are
      essential. These would improve quality of life, reduce personal and national
      expenditure, and help increase national economy.

PMID- 27893671
TI  - Scoliosis secondary to lumbar osteoid osteoma: A case report of delayed diagnosis
      and literature review.
AB  - RATIONALE: Lumbar osteoid osteoma has a low incidence, which could easily lead to
      scoliosis. PATIENT CONCERNS: Scoliosis secondary to lumbar osteoid osteoma could
      be easily misdiagnosed when patients do not complain of obvious symptoms.
      DIAGNOSES: We reported a case of a 9-year-old boy with back deformity that was
      firstly diagnosed with scoliosis at the local hospital. After prescribed with
      orthosis, the patient experienced aggravating pain that could not be relieved
      with painkillers. After he admitted to our hospital for further medical advice,
      he was prescribed to complete radiological examinations. Considering his
      radiological examination results and his medical history, correct diagnosis of
      lumbar osteoid osteoma was made. INTERVENTIONS: Surgical intervention of
      posterior lesion resection was conducted after diagnosis. Intra-operative frozen
      pathology indicated features of osteoid osteoma. As the lesion involved inferior
      articular process of L5, which could cause lumbar instability after lesion
      resection, internal fixation was conducted at L4-S1 segment, and posterolateral
      bone fusion was also conducted at L5-S1 segment. OUTCOMES: Three months after
      operation, the patient showed marked improvement of scoliosis deformity and great
      relief of lumbar pain. LESSONS SUBSECTIONS: Although spine osteoid osteoma is
      clinically rare, it shall not be overlooked when young patients present with
      scoliosis first. Radiological results including computed tomography and magnetic
      resonance imaging shall be taken carefully as reference when making diagnosis.
      Surgical intervention of lesion resection could well improve scoliosis and
      relieve lumbar pain.

PMID- 27893670
TI  - Epidemiology and clinical characteristics of traumatic brain injury in Lebanon: A
      systematic review.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a debilitating medical and emerging
      public health problem that is affecting people worldwide due to a multitude of
      factors including both domestic and war-related acts. The objective of this paper
      is to systematically review the status of TBI in Lebanon - a Middle Eastern
      country with a weak health system that was chartered by several wars and
      intermittent outbursts of violence - in order to identify the present gaps in
      knowledge, direct future research initiatives and to assist policy makers in
      planning progressive and rehabilitative policies. METHODS: OVID/Medline, PubMed,
      Scopus databases and Google Scholar were lastly searched on April 15, 2016 to
      identify all published research studies on TBI in Lebanon. Studies published in
      English, Arabic or French that assessed Lebanese patients afflicted by TBI in
      Lebanon were warranting inclusion in this review. Case reports, reviews,
      biographies and abstracts were excluded. Throughout the whole review process,
      reviewers worked independently and in duplicate during study selection, data
      abstraction and methodological assessment using the Downs and Black Checklist.
      RESULTS: In total, 11 studies were recognized eligible as they assessed Lebanese
      patients afflicted by TBI on Lebanese soils. Considerable methodological
      variation was found among the identified studies. All studies, except for two
      that evaluated domestic causes such as falls, reported TBI due to war-related
      injuries. Age distribution of TBI victims revealed two peaks, young adults
      between 18 and 40 years, and older adults aged 60 years and above, where males
      constituted the majority. Only three studies reported rates of mild TBI.
      Mortality, rehabilitation and systemic injury rates were rarely reported and so
      were the complications involved; infections were an exception. CONCLUSION:
      Apparently, status of TBI in Lebanon suffers from several gaps which need to be
      bridged through implementing more basic, epidemiological, clinical and
      translational research in this field in the future.

PMID- 27893672
TI  - Risk factors of severe hypoglycemia requiring medical assistance and neurological
      sequelae in patients with diabetes: A case-control study.
AB  - Hypoglycemia commonly occurs in patients who are being treated for diabetes. In
      some cases, these patients suffer from severe hypoglycemia that requires medical
      assistance and which can unfortunately result in long-term disabilities.
      Therefore, we investigated risk factors associated with severe hypoglycemia
      requiring medical assistance (HMA) and the resulting neurological sequelae in
      patients with diabetes. This investigation was a case-control study that assessed
      129 patients with diabetes and documented hypoglycemia from a single tertiary
      hospital between February 2013 and May 2015. They were treated with oral
      hypoglycemic agents alone (54%) or with insulin with/without oral hypoglycemic
      agents (46%). If a patient with diabetes visited the emergency department due to
      hypoglycemia, this was defined as HMA. The control group was composed of patients
      with documented, nonsevere hypoglycemia who visited the outpatient clinic during
      the same period. The degree of neurological disability in the HMA patients was
      measured using the modified Rankin Scale. A multivariate analysis revealed that
      independent risk factors of HMA were associated with a lack of the self
      monitoring of blood glucose (SMBG) and previous episodes of severe hypoglycemia.
      In the HMA group, 15 patients (22%) had neurological sequelae at the time of
      discharge. Patients with neurological sequelae were older than those without
      sequelae (74.3 years vs 65.8 years, P = 0.006) and had increased psychological
      evidence of disorders such as insomnia, dementia, and depression (40% vs 11%, P =
      0.017). Patients with sequelae were also more likely to live in rural areas (47%
      vs 19%, P = 0.04) and to have a longer time from last seen normal till glucose
      administration (5.2 hours vs 1.6 hours, P = 0.027). In the present study, absence
      of SMBG and previous severe hypoglycemic episodes were independent risk factors
      of HMA and patients with an older age, a psychological disorder, a rural
      residence, and a prolonged duration of hypoglycemia had higher risks of
      neurological sequelae. Therefore, the present findings suggest that physicians
      should aim to prevent hypoglycemia in patients with a history of hypoglycemia and
      provide education for these patients regarding regular SMBG.

PMID- 27893673
TI  - Risk factor and outcome for intra-abdominal bleeding in patients with
      enterocutaneous fistula.
AB  - Intra-abdominal bleeding is a major and lethal complication in patients with
      enterocutaneous fistula (ECF) while few studies are involved in this aspect. In
      the present study, we aimed to investigate the risk factors and assessed the
      outcome for intra-abdominal bleeding in patients with ECF.A retrospective study
      was performed from October 2013 to October 2015. Medical records of 67 ECF
      patients with intra-abdominal bleeding and 134 ECF patients without intra
      abdominal bleeding matched as controls were reviewed and analyzed. Logistic
      regression was performed to evaluate the risk factor of intra-abdominal bleeding
      in patients with ECF. Outcomes such as mortality, hospital durations, and cost
      were compared between ECF patients with or without intra-abdominal bleeding.A
      total of 67 ECF patients suffered intra-abdominal bleeding during
      hospitalization. In the logistic regression, duodenum fistula (odds ratio [OR]:
      3.899, 95% confidence interval [CI]: 1.204-12.634, P = 0.023), hemorrhage history
      (OR: 15.846 95% CI: 5.779-43.448, P < 0.001), and acute kidney injury (OR: 6.350
      95% CI: 2.033-19.836, P = 0.001) were independent risk factors for intra
      abdominal bleeding in patients with ECF. In addition, the bleeding patients
      showed a significantly higher mortality rate, prolonged total parenteral
      nutrition days, hospital and intensive care unit durations, more complications,
      and increased cost.We revealed the 3 risk factors for intra-abdominal bleeding
      among ECF patients. Besides, intra-abdominal hemorrhage was associated with a
      poor prognosis in patients with ECF.

PMID- 27893674
TI  - Relapsing-remitting lesions in a woman with progressive hemifacial atrophy and
      chronic hepatitis B virus infection: A case report.
AB  - INTRODUCTION: Progressive hemifacial atrophy (PHA) is a rare disorder
      characterized by unilateral facial atrophy affecting the skin, subcutaneous
      tissue, and fat, muscle, and osteocartilagenous structures creating a sunken
      hemiface appearance.Etiopathogenesis of PHA is poorly understood; no definitive
      treatment is currently available. CLINICAL FINDINGS: We report a 41-year-old
      woman with PHA who showed an uncharacteristic "relapsing-remitting" evolution of
      brain lesions and was seropositive for hepatitis B virus (HBV). She presented
      with a history of recurrent tonic-clonic seizures. Magnetic resonance imaging
      (MRI) showed progressive atrophy and multiple white matter lesions in the left
      side of the brain. Interestingly, the serial MRI examination (4 MRI scans over a
      period of 9 years) showed a "relapsing-remitting" pattern of brain lesions akin
      to that observed in a subtype of multiple sclerosis. Autoimmune-related
      investigations revealed increased serum levels of immunoglobulin (Ig) G, anti
      nuclear antibody (ANA), and gamma-IgG. Infection is considered as one of the
      possible causes of PHA. However, the association of peripheral infection such as
      HBV infection with PHA has not been reported. CONCLUSION: Our experience with
      this case suggests that PHA may have a relapsing-remitting disease course.
      Autoimmune inflammatory response to chronic HBV infection may have triggered the
      relapse in this case. This case underlines a novel etiopathogenetic mechanism of
      PHA.

PMID- 27893675
TI  - A multicenter, randomized, double-blind trial comparing the efficacy and safety
      of TUDCA and UDCA in Chinese patients with primary biliary cholangitis.
AB  - AIM: Tauroursodeoxycholic acid (TUDCA) is a taurine conjugated form of
      ursodeoxycholic acid (UDCA) with higher hydrophility. To further evaluate the
      efficacy and safety of TUDCA for primary biliary cholangitis (PBC), we performed
      this study on Chinese patients. METHODS: 199 PBC patients were randomly assigned
      to either 250 mg TUDCA plus UDCA placebo or 250 mg UDCA plus TUDCA placebo, 3
      times per day for 24 weeks. The primary endpoint was defined as percentage of
      patients achieving serum alkaline phosphatase (ALP) reduction of more than 25%
      from baseline. RESULTS: At week 24, 75.97% of patients in the TUDCA group and
      80.88% of patients in the UDCA group achieved a serum ALP reduction of more than
      25% from baseline (P = 0.453). The percentage of patients with serum ALP levels
      declined more than 40% following 24 weeks of treatment was 55.81% in the TUDCA
      group and 52.94% in the UDCA group (P = 0.699). Both groups showed similar
      improvement in serum levels of ALP, aspartate aminotransferase, and total
      bilirubin (P > 0.05). The proportion of patients with pruritus/scratch increased
      from 1.43% to 10.00% in UDCA group, while there's no change in TUDCA group (P =
      0.023). Both drugs were well tolerated, with comparable adverse event rates
      between the 2 groups. CONCLUSIONS: TUDCA is safe and as efficacious as UDCA for
      the treatment of PBC, and may be better to relieve symptoms than UDCA.

PMID- 27893676
TI  - Combination use of paclitaxel and avastin enhances treatment effect for the NSCLC
      patients with malignant pleural effusion.
AB  - The current study is conducted to investigate efficacy of the chemotherapy drug
      paclitaxel in combination with Avastin (Roche Diagnostics GmbH., Mannheim,
      Germany) (antiangiogenic agent) in treatment of malignant pleural effusions
      (MPEs).Twenty-four patients with non-small cell lung cancer were randomly
      assigned for 2 treatment approaches. Ten patients received paclitaxel (175 mg/m)
      alone, and 14 patients took a combination therapy of paclitaxel and Avastin (5
      mg/kg). Efficacy of the treatment approaches in the patients was validated with
      the change in the MPE volume. Pharmacokinetic (PK) profile and urinary excretion
      rate of paclitaxel were analyzed with serum vascular endothelial growth factor
      (VEGF) level, and adverse events were examined as well.The combination therapy
      reduced the MPE level with a successful rate of 29% and a survival rate of 25%
      over the single paclitaxel treatment in the study cohort (both P < 0.05). PKs for
      the combined treatment displayed a rapid distribution of the anticancer drug
      paclitaxel with an obvious increase in its elimination half-life in the pleural
      fluid (both P < 0.01). Mean residence time of paclitaxel increased in the
      presence of Avastin (P < 0.01). Serum VEGF levels significantly reduced in the
      Avastin-treated patients as compared to the paclitaxel-treated ones (P < 0.01).
      The urinary excretion rate was similar in the study cohort. Incidence of adverse
      events for the 2 treatment approaches was similar in the patients.Intervention of
      Avastin enhances potency of paclitaxel in treatment of MPEs with the increased
      survival rate of the patients through inhibiting VEGF production and prolonging
      time of ongoing interaction between the chemotherapy drug and the tumor tissues.

PMID- 27893677
TI  - Impact of iron deficiency anemia on the function of the immune system in
      children.
AB  - The importance of iron deficiency as a public health problem is based ultimately
      on the seriousness of its consequences on health. The most extensively
      investigated consequences of iron deficiency involve work performance and immune
      function. The significance of the effects on work performance is generally
      accepted. In contrast, data on the influence of iron deficiency on immune
      function are often perceived as being confusing and contradictory.We aimed to
      evaluate the effect of iron deficiency anemia on humoral, cellular, nonspecific
      immunity, and also the effect on the cytokines that are the key factors of many
      immunologic steps.Forty children with iron deficiency anemia and 20 age and sex
      matched healthy children were included. All children were subjected to full
      medical history, thorough clinical examination, complete blood count, iron
      indices (serum iron, serum total iron-binding capacity, serum ferritin, and
      transferrin saturation), immunoglobulin assay (IgA, IgG, and IgM), interleukin
      (IL)-6 serum level, study of T-lymphocyte subsets, and evaluation of phagocytic
      function of macrophages and oxidative burst activity of neutrophils.Patients had
      significantly lower IgG levels, IL-6, phagocytic activity, and oxidative burst of
      neutrophils than controls, although there was no significant difference between
      patients and controls with regard to other immunoglobulins and CD4/CD8 ratio.
      There was significantly positive correlation between serum iron and IL-6 serum
      level.We concluded that humoral, nonspecific immunity (phagocytic activity and
      oxidative burst), and the IL-6 are influenced in patients with iron deficiency
      anemia. Study of these abnormalities after correction of iron deficiency is
      strongly needed.

PMID- 27893678
TI  - Value of cyclin A immunohistochemistry for cancer risk stratification in Barrett
      esophagus surveillance: A multicenter case-control study.
AB  - The value of endoscopic Barrett esophagus (BE) surveillance based on histological
      diagnosis of low-grade dysplasia (LGD) remains debated given the lack of adequate
      risk stratification. The aim of this study was to evaluate the predictive value
      of cyclin A expression and to combine these results with our previously reported
      immunohistochemical p53, AMACR, and SOX2 data, to identify a panel of biomarkers
      predicting neoplastic progression in BE.We conducted a case-control study within
      a prospective cohort of 720 BE patients. BE patients who progressed to high-grade
      dysplasia (HGD, n = 37) or esophageal adenocarcinoma (EAC, n = 13), defined as
      neoplastic progression, were classified as cases and patients without neoplastic
      progression were classified as controls (n = 575). Cyclin A expression was
      determined by immunohistochemistry in all 625 patients; these results were
      combined with the histological diagnosis and our previous p53, AMACR, and SOX2
      data in loglinear regression models. Differences in discriminatory ability were
      quantified as changes in area under the ROC curve (AUC) for predicting neoplastic
      progression.Cyclin A surface positivity significantly increased throughout the
      metaplasia-dysplasia-carcinoma sequences and was seen in 10% (107/1050) of biopsy
      series without dysplasia, 33% (109/335) in LGD, and 69% (34/50) in HGD/EAC.
      Positive cyclin A expression was associated with an increased risk of neoplastic
      progression (adjusted relative risk (RR) 2.4; 95% CI: 1.7-3.4). Increases in AUC
      were substantial for P53 (+0.05), smaller for SOX2 (+0.014), minor for cyclin A
      (+0.003), and none for AMARC (0.00).Cyclin A immunopositivity was associated with
      an increased progression risk in BE patients. However, compared to p53 and SOX2,
      the incremental value of cyclin A was limited. The use of biomarkers has the
      potential to significantly improve risk stratification in BE.

PMID- 27893680
TI  - The value of eZIS analysis of Tc-99m ECD SPECT on identifying cerebellar
      hypoperfusion in a patient with superficial siderosis: A case report.
AB  - INTRODUCTION: Brain perfusion single photon computed tomography (SPECT) is a
      functional imaging modality and has been widely utilized in evaluation of various
      kinds of neurological disorders. Easy z-score imaging system (eZIS) is a computer
      assisted statistical analysis, based on the comparison with age-classified ethyl
      cysteinate dimer (ECD) normal database, which provides objectively interpretation
      of Tc-99m ECD brain perfusion SPECT.Here we presented a 64-year-old male with
      dizziness, spin sensation, nausea, and vomiting in the emergency room, and brain
      computed tomography scan showed only small hypodensity lesion in cerebellum. Tc
      99m ECD SPECT was performed for evaluating occult cerebral ischemia, infarction,
      and/or degeneration, but no remarkable abnormality could be identified by
      experienced readers on conventional display. The result of eZIS showed remarkable
      hypoperfusion in cerebellum and mild hypoperfusion in bilateral frontal and
      parietal lobes. Magnetic resonance imaging (MRI) confirmed severe atrophy of
      anterior cerebellar lobe. In addition, MRI showed diffuse hypointensity signals
      along with cerebrospinal fluid spaces, especially those areas with hypoperfusion
      on SPECT, compatible with typical appearances of superficial siderosis.
      CONCLUSION: This presented case demonstrates the value of software analysis with
      eZIS on enhancing the diagnostic value of brain perfusion SPECT for detecting
      brain lesions at an uncommon location due to a rare disease.

PMID- 27893679
TI  - Pelvic inflammatory disease increases the risk of a second primary malignancy in
      patients with cervical cancer treated by surgery alone.
AB  - As the number of long-term cervical cancer survivors continues to increase
      because of improvements in treatment, concerns about second primary malignancy
      have grown. The high-risk area of second primary cancers in cervical cancer
      survivors is the pelvis. Pelvic inflammatory disease (PID) could be a useful
      marker for gynecological cancers. Thus, we designed a large-scale, nationwide,
      controlled cohort study to investigate whether PID or other risk factors
      increased the risk of second primary cancers in patients with cervical cancer
      treated by surgery alone.Between 2000 and 2010, a total of 24,444 cervical cancer
      patients were identified using the Registry Data for Catastrophic Illness and the
      National Health Insurance Research Database (NHIRD) of Taiwan. Patients who
      received definite surgery were selected. To exclude the effect on second primary
      malignancy by treatment modalities, all cervical patients who ever having
      received adjuvant or definite radiotherapy or chemotherapy for primary cervical
      cancer were excluded. Finally, 3860 cervical cancer patients treated by surgery
      alone without adjuvant treatments were analyzed.Cox proportional hazards model
      was used for multivariate analysis and the Kaplan-Meier method was used to assess
      the cumulative risks. Regarding the incidence of second primary cancers, the
      standardized incidence ratio (SIR) was used.The median follow-up time was 56.6
      months. The 6-year cumulative risk of second primary cancers is 0.16% and 0.12%
      for PID and without PID, respectively. After adjustment for confounders, age of
      less than 50 years, the presence of diabetes mellitus, and PID were significantly
      positivity associated with the risk of second primary cancers. The hazard ratios
      (HRs) of age less than 50 years, diabetes mellitus, and PID were 1.38 (95% CI =
      1.11-2.04), 1.40 (95% CI = 1.06-1.85), and 1.35 (95% CI = 1.00-1.81),
      respectively. A higher incidence of second primary cancers was observed in the
      genitals, bladder, and colon.In conclusion, the incidence of second primary
      cancers was higher in the genitals, bladder, and colon in patients with cervical
      cancer treated with surgery alone. The patients with PID had a higher risk of
      second primary cancers.

PMID- 27893681
TI  - Combination of transcatheter arterial chemoembolization and CT-guided
      percutaneous segment ablation for hepatocellular carcinoma therapy: A
      retrospective study.
AB  - Treatment option for liver cancer patients with large tumor >5 cm and/or portal
      vein tumor thrombosis is very limited. New treatment strategy is badly needed.
      Our study is to determine the safety and treatment efficacy of a new minimally
      invasive treatment strategy-liver segment thermal ablation.Late-stage
      hepatocellular carcinoma patients were included and treated with percutaneous
      ablation to destroy the entire tumor-containing liver segment to reduce
      reoccurrence and prolong survival. Transcatheter arterial chemoembolization was
      used before ablation to label tumor margin. The patients were followed up
      routinely.The patients were followed up for 8 to 95 months. Mean overall survival
      (OS) (n = 6) was 21.5 months (range 8-95). For patients in BCLC stage B (n = 2),
      average OS was 16 months; for those in stage C (n = 4), mean OS was 25 months
      (range 15-95). Out of all 6 patients, 2 reoccurred within 1 year, and 1
      reoccurred after 13 months postoperatively. The average alpha-fetoprotein was
      dropped from 1153.69 to 41.22 MUg/L postoperatively. No severe intra or
      postoperative complications were observed.Our preliminary data indicated that
      transcatheter arterial chemoembolization + segment ablation is safe and benefits
      survival significantly for late-stage hepatocellular carcinoma patients. A
      prospective multicenter, randomized trial comparing focal and segment ablation is
      now ongoing in China (Trial Registry Number, ChiCTR-TRC-12002786).

PMID- 27893682
TI  - Peritoneal dialysis-related peritonitis due to Halomonas hamiltonii: A first case
      report.
AB  - INTRODUCTION: Halomonas hamiltonii is a Gram-negative, halophilic, motile, and
      nonspore-forming rod bacterium. Although most Halomonas sp. are commonly found in
      saline environments, it has rarely been implicated as a cause of human infection.
      Herein, the authors present a case report of continuous ambulatory peritoneal
      dialysis (CAPD)-related peritonitis attributed to H hamiltonii. CASE
      PRESENTATION: An 82-year-old male patient who had been receiving CAPD therapy
      presented to an emergency department with complaints of abdominal pain and cloudy
      dialysate that had persisted for 2 days. The peritoneal dialysate was compatible
      with CAPD peritonitis, with white blood cell count of peritoneal effluent of
      810/mm and neutrophils predominated (60%). Two days after culture on blood agar
      medium, nonhemolytic pink mucoid colonies showed, with cells showing Gram
      negative, nonspore-forming rods with a few longer and larger bacilli than usual
      were found. We also performed biochemical tests and found negative responses in
      K/K on the triple sugar iron test and H2S and equivocal (very weak) response in
      the motility test, but positive responses to catalase, oxidase, and urease tests.
      The partial sequence of the 16S rRNA gene of a bacterium detected by peritoneal
      fluid culture was utilized for a Basic Local Alignment Search Tool search, which
      revealed that the organism was H hamiltonii. Intraperitoneal antibiotics were
      administered for 21 days, and the patient was discharged without clinical
      problems. CONCLUSION: We present here the first case report of CAPD-related
      peritonitis caused by H hamiltonii, which was identified using molecular
      biological techniques. Although guidelines do not exist for the treatment of
      infections caused by this organism, conventional treatment for Gram-negative
      organisms could be effective.

PMID- 27893683
TI  - Clinical characteristics of early- and late-onset gout: A cross-sectional
      observational study from a Chinese gout clinic.
AB  - A retrospective cross-sectional study using data from an outpatient clinic in
      China was conducted to investigate the clinical features of early-onset gout
      patients.All patients diagnosed with gout were asked about clinical
      characteristics of their gout and comorbid diseases. Patients presenting with
      acute flares were asked about common triggers before the flare. "Early-onset"
      gout was defined as onset of gout before 40 years and "late-onset" as onset >=40
      years. Major joint involvement, flare frequency before presentation, the
      cumulative number of involved joints, proportions of tophi complications at
      presentation, flare triggers, as well as any metabolic, cardiovascular,
      cerebrovascular, and renal comorbidities, were compared between the 2 groups.A
      total of 778 gout patients were enrolled in this study, including 449 (57.7%) in
      the early-onset group and 329 (42.3%) in the late-onset group. Compared with the
      late-onset gout patients, the early-onset gout patients had a higher proportion
      of ankle/mid-foot involvement (62.8% vs 48.2%, P < 0.001), more frequent flares
      before presentation (11.2 +/- 1.17 vs 6.97 +/- 1.03 times per year, P = 0.01),
      higher cumulative number of involved joints (5.2 +/- 0.26 vs 3.8 +/- 0.26, P <
      0.001), and more likely to have alcohol consumption as a flare trigger (65.2% vs
      53.9%, P = 0.03); whereas early-onset gout patients had fewer metabolic,
      cardiovascular, cerebrovascular, or renal complications.Early- and late-onset
      gout patients had different clinical features. Early-onset seems to be influenced
      more by lifestyle, while late-onset patients have more complications because of
      comorbidities.

PMID- 27893684
TI  - CT findings of small cell lung carcinoma: Can recognizable features be found?
AB  - The purpose of this study was to clarify the recognizable computed tomography
      (CT) features of small cell lung carcinoma (SCLC).Contrast enhanced CT scans were
      reviewed retrospectively for mass location, mediastinal extension, and other
      concomitant findings in 142 patients with pathologically proven SCLC. SCLC was
      classified into hilar mass only (type I), hilar mass with ipsilateral mediastinal
      extension (type II), hilar mass with bilateral mediastinal extension (type III),
      and peripheral mass (type IV). When mediastinal lymphadenopathy (m-LAP) was
      indistinguishable from a hilar mass, we defined it as a mediastinal conglomerate
      mass (m-CM). Type IIa or IIIa had ipsilateral or bilateral m-LAP and type IIb,
      IIIb or IIIc had ipsilateral or bilateral m-CM.Type I (n = 8, 5.6%), type II (n =
      58, 40.8%), type III (n = 55, 38.8%), and type IV (n = 21, 14.8%) were
      manifested. The combination of a hilar mass and m-CM was found in 68 patients
      (47.9%). Type IV masses showed lobulation in 11, microlobulation in 4, both
      lobulated and irregular margins in 4, and spiculation in 2. A total of 120
      patients (84.5%) had a bronchial stenosis/obstruction; single (n = 52) and 2 or
      more (n = 68). Ninety-five patients (67.0%) had vascular invasion including
      main/lobar pulmonary artery and superior vena cava, and 55 (38.7%) had pleural
      effusion and/or pleural nodules. Concomitant parenchymal findings (n = 92, 64.8%)
      were noted: contiguous consolidation/nodule (n = 45), hematogeneous spread (n =
      32), lymphangitic spread (n = 21), obstructive pneumonia (n = 22), and
      obstructive atelectasis (n = 14).In conclusion, the recognizable CT features of
      SCLC were a hilar mass with m-CM. Most of the hilar masses showed 2 or more
      bronchial stenoses/obstructions. Most cases of peripheral SCLC manifested as a
      lobulated mass rather than a spiculated mass. Vascular invasion and concomitant
      parenchymal findings were observed commonly.

PMID- 27893685
TI  - Acute liver failure caused by hemophagocytic lymphohistiocytosis in adults: A
      case report and review of the literature.
AB  - BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare condition that can
      be caused by a primary or acquired disorder of uncontrolled immune response.
      Liver injury is a common complication of HLH; however, HLH presenting as acute
      liver failure (ALF) has rarely been reported in adults. CASE SUMMARY: A 34-year
      old man was admitted to our hospital with nausea and fatigue persisting for 2
      weeks and jaundice for 1 week. He had hyperthermia at the onset of disease. At
      admission, he had severe liver injury with unknown etiology. The laboratory data
      showed that he had hyperferritinemia, thrombocytopenia, anemia,
      hypertriglyceridemia, and hypofibrinogenemia. Finally, a bone marrow biopsy
      revealed hemophagocytic cells, and he was diagnosed with HLH. The patient was
      treated with prednisone and plasma exchange. However, the liver function of the
      patient deteriorated, and he finally died of multiorgan failure. CONCLUSIONS:
      Reports of adult patients with ALF caused by HLH have increased, and HLH should
      be suspected in patients with ALF of indeterminate cause. Although the efficacy
      of the treatment strategy recommended by the HLH 2004 remains to be confirmed in
      adult patients with ALF caused by HLH, early diagnosis and prompt combined
      treatment with steroids and cyclosporin A or etoposide should be emphasized.

PMID- 27893686
TI  - Association between cigarette smoking and interleukin-17A expression in nasal
      tissues of patients with chronic rhinosinusitis and asthma.
AB  - Cigarette smoke plays a substantial role in the development of airway
      inflammatory diseases, including asthma and chronic rhinosinusitis (CRS).
      Interleukin (IL)-17A might contribute to cigarette smoke-related inflammation of
      the airway. This study aimed to investigate the association between cigarette
      smoking and IL-17A expression in the nasal tissues of patients with CRS and
      asthma.We prospectively recruited 24 patients (13 smokers, 11 nonsmokers) with
      CRS and asthma and 6 patients with asthma but without CRS (control group) in a
      tertiary medical center. Nasal mucosa was obtained as part of the nasal surgery.
      Protein and mRNA levels of IL-17A in the nasal tissues were determined by
      immunostaining and real-time polymerase chain reaction.The number of unexpected
      emergency clinic visits for acute asthma attacks were higher among smokers than
      among nonsmokers. Interleukin-17A protein and mRNA levels in the nasal tissues of
      smokers were greater compared to those in the nasal tissues of nonsmokers (P =
      0.02 both) and control patients (P = 0.05 and 0.04, respectively).Cigarette
      smoking was associated with an increase in the number of unexpected emergency
      clinic visits due to acute asthma attack and in the expression of IL-17A in the
      nasal tissues of patients with airway inflammatory diseases.

PMID- 27893687
TI  - Spontaneous and transient predinner hyperglycemia in some patients with diabetes:
      Dusk phenomenon.
AB  - Blood glucose fluctuations have higher risk than absolute blood glucose level in
      diabetic chronic complications. At present, "dawn phenomenon" is well known by
      clinicians, but "dusk phenomenon" has not been recognized. This study explored
      the objective existence of "dusk phenomenon" (spontaneous and transient predinner
      hyperglycemia) and its clinical significance.The data of 54 patients with
      diabetes, who received routine insulin pump therapy between December 2010 and
      October 2012 in our hospital, were retrospectively analyzed. These patients
      included 4 patients with type 1 diabetes mellitus (DM) (T1DM) and 50 patients
      with type 2 DM (T2DM). According to the difference between predinner and
      postlunch blood glucose levels, the 50 patients with T2DM were divided into dusk
      phenomenon group (4 patients, all the differences >=0 mmol/L during insulin pump
      therapy), nondusk phenomenon group (12 patients, all the differences <0 mmol/L
      during insulin pump therapy), and suspicious group (34 patients, the differences
      were uncertain during insulin pump therapy). In the 4 patients with T1DM of this
      study, the differences all were more than 0 mmol/L during insulin pump therapy.
      The changes in blood glucose levels were observed, and the correlations of blood
      glucose level with other factors were analyzed in T1DM and T2DM patients,
      respectively.In T1DM patients, blood glucose level was significantly higher in
      predinner than in prebreakfast and prelunch (all P < 0.01), and in postdinner 2
      hour than in postlunch 2 hour (P = 0.021). The predinner blood level had no
      significant correlations with the blood glucose level at other time points and
      insulin dosages (all P > 0.05). In T2DM patients, the predinner blood glucose
      level was significantly higher in dusk phenomenon group than in suspicious group
      and nondusk phenomenon group (all P < 0.05). In dusk phenomenon group, the blood
      glucose level remained rising from predinner to prebed, and the predinner blood
      glucose level was only significantly correlated with postdinner 2-hour blood
      glucose level (P < 0.05).The "dusk phenomenon" (spontaneous and transient
      predinner hyperglycemia) is an objective existence in some patients with
      diabetes. The predinner hyperglycemia can affect blood glucose control between
      postdinner and prebed. Awareness of the "dusk phenomenon" has important clinical
      significance.

PMID- 27893688
TI  - Identification of genes and signaling pathways associated with diabetic
      neuropathy using a weighted correlation network analysis: A consort study.
AB  - BACKGROUND: The molecular mechanisms behind diabetic neuropathy remains to be
      investigated. METHODS: This is a secondary study on microarray dataset (GSE24290)
      downloaded from Gene Expression Omnibus (GEO) at the National Center for
      Biotechnology Information (NCBI), which included 18 nerve tissue samples of
      progressing diabetic neuropathy (fibers loss >=500 fibers/mm) and 17 nerve tissue
      samples of nonprogressing diabetic neuropathy (fibers loss <=100 fibers/mm).
      Differentially expressed genes (DEGs) were screened between progressing and
      nonprogressing diabetic neuropathy. With the DEGs obtained, a weighted gene
      coexpression network analysis was conducted to identify gene clusters associated
      with diabetic neuropathy. Diabetes-related microRNAs (miRNAs) and their target
      genes were predicted and mapped to the genes in the gene clusters identified.
      Consequently, a miRNA-gene network was constructed, for which gene ontology (GO)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was
      performed. Potential drugs for treatment of diabetic neuropathy were also
      predicted. RESULTS: Total 370 upregulated and 379 downregulated DEGs were
      screened between nonprogressing and progressing diabetic neuropathy. Has-miR-377,
      has-miR-216a, and has-miR-217 were associated with diabetes. Inflammation was the
      most significant GO term. The peroxisome proliferator-activated receptor (PPAR)
      pathway and the adenosine monophosphate (AMP)-activated protein kinase (AMPK)
      signaling pathway were significantly KEGG pathways significantly enriched with
      PPAR gamma (PPARG), stearoyl-CoA desaturase (SCD), cluster of differentiation 36
      (CD36), and phosphoenolpyruvate carboxykinase 1 (PCK1). CONCLUSION: The study
      suggests that PPARG, SCD, CD36, PCK1, AMPK pathway, and PPAR pathway may be
      involved in progression of diabetic neuropathy.

PMID- 27893689
TI  - A new method for insertion of long intestinal tube for small bowel obstruction:
      Nonendoscopic over-the-wire method via short nasogastric tube.
AB  - It is often difficult to insert a long intestinal tube (LT) in patients with
      small bowel obstruction (SBO). We developed a novel technique for inserting an LT
      without endoscopy called nonendoscopic over-the-wire method via short nasogastric
      tube (NEWSt). We evaluated the efficacy and safety of NEWSt.We performed a
      retrospective study of patients who underwent LT insertion for SBO without any
      indications of strangulation with either NEWSt (n = 16) or endoscopy (n = 17)
      between November 2011 and February 2015 at our hospital. Univariate analysis was
      used to assess the success rate of LT placement beyond the duodenojejunal
      flexure, time required for the procedure, clinical outcomes, and adverse
      events.The success rate was 100% in both groups. Procedure time was numerically,
      but not statistically, shorter in the NEWSt group compared with the endoscopy
      group (24 +/- 13 vs 30 +/- 13 min; P = 0.174). There were no statistically
      significant differences between the 2 groups in terms of surgery rate (31% vs
      12%; P = 0.225), fasting period (11.3 +/- 6.3 vs 9.9 +/- 4.5 days; P = 0.482),
      hospital stay (26.4 +/- 22.1 vs 18.7 +/- 7.0 days; P = 0.194), and recurrence
      rate (19% vs 24%; P = 1.0). No serious adverse event was observed in the NEWSt
      group, whereas serious aspiration pneumonia was observed in 2 patients after LT
      insertion in the endoscopy group.Without endoscopy, NEWSt enabled the high
      success rate and the short procedure time for the LT insertion. Prospective,
      randomized controlled trials are needed.

PMID- 27893690
TI  - Prognosis of papillary thyroid carcinoma in elderly patients after thyroid
      resection: A retrospective cohort analysis.
AB  - The size of the elderly population and the incidence of papillary thyroid
      carcinoma (PTC) in this group appear to be rapidly increasing, although published
      information based on more detailed older age groupings are lacking.This study
      aimed to determine the clinical features and outcomes of elderly patients in
      PTC.All consecutive patients who received surgery for PTC in our Department from
      1978 to 2014 were included. We compared 3 patient groups: young (<65 years),
      older (65-75 years), and very old patients (>75 years). Total thyroidectomy was
      performed with lymph node (LN) dissection in most cases, and radioiodine therapy
      was administered as needed.A total of 3835 patients (3257 young patients, 450
      older patients, and 128 very old patients) were identified. Very old patients
      were more likely to have advanced (III/IV) tumor, nodes, metastases (TNM) stage,
      greater tumor size, number of tumors, and extracapsular invasion compared with
      young and older patients. For the 2289 patients with LN dissection (60%),
      metastatic LNs were more frequent in the very old group (44%) than in the other
      groups (34% young and 33% older patients) (P = 0.01). Very old patients had more
      frequent distant metastases (5%) than the older (2%) and young groups (1%) (P <
      0.001). The overall postoperative morbidity was not significantly different
      between the 3 age groups. Recurrence was documented in 202 (6.2%) young, 29
      (6.4%) older, and 15 (11.7%) very old PTC patients (P = 0.04). The 5-year disease
      free survival was 81.3% for very old, 92.9% for older, and 94.7% for young group
      (P < 0.001).Very old patients should be considered high-risk PTC patients and
      their therapeutic strategy may benefit from aggressive treatment.

PMID- 27893691
TI  - Valuable hematological indicators for the diagnosis and severity assessment of
      Chinese children with community-acquired pneumonia: Prealbumin.
AB  - Chest X-ray is a "golden standard" for the diagnosis and severity assessment of
      community-acquired pneumonia (CAP). However, it cannot be used as routine
      examination of CAP in children. The present study aims to investigate the roles
      of prealbumin (PA) in CAP in children and further determine the usefulness of PA
      in diagnosis and severity assessment of CAP in children.This was a retrospective
      analysis of 174 cases of hospitalized children with CAP. The following indicators
      were recorded: vital sign, inflammatory indexes, PA, and respiratory pathogens
      immunoglobulin M antibody test results. A total of 33 healthy children were
      selected as the control group. The results of laboratory tests between CAP and
      control groups were compared. CAP group was further divided into mild CAP and
      severe CAP groups, and vital signs and laboratory examination results of 2 groups
      were compared.The total positive rate of Mycoplasma pneumoniae in this study was
      27.4%, and there was no significant difference in different seasons (P = 0.356).
      Compared with controls, there was no significant difference between procalcitonin
      and C-reactive protein in CAP group (P = 0.355, 0.061). The white blood cell
      count, percentage of neutrophils, neutrophil count, and erythrocyte sedimentation
      rate in the CAP group were significantly higher than those in control group, and
      PA was significantly lower than that in the control group (all P < 0.05). In the
      traditional cutoff value (<170 mg/L), the sensitivity of PA for the diagnosis of
      CAP was 0.847, which was significant higher than traditional inflammatory
      indicators. Moreover, it was found that PA was an independent protective factor
      for CAP in children based on multivariate analysis (odds ratio: 0.974; 95%
      confidence interval: 0.956-0.993; P = 0.008). PA level in severe CAP group was
      significantly lower than in mild CAP group (P = 0.001). With a cutoff value of
      125 mg/L, the sensitivity and specificity of PA for the severity assessment of
      CAP were 0.703 and 0.714, respectively.Combined with traditional inflammatory
      markers, PA may improve the diagnostic efficacy of CAP in children. PA can be
      used as a reference marker to complement the chest X-rays for severity assessment
      of children CAP.

PMID- 27893692
TI  - Relationship between serum uric acid and metastatic and nonmetastatic rectal
      cancer patients with undergoing no chemotherapy.
AB  - The aim of this study was to investigate the role of uric acid (UA) in assessing
      rectal cancer metastasis.There were 475 newly diagnosed patients with complete
      data in our study, a total of 475 cases were reviewed, and divided into patients
      with metastasis and without metastasis.There were several statistical differences
      in age, tumor diameter, carcino-embryonic antigen (CEA), and C-reactive protein
      (CRP) between the 2 groups. Importantly, serum concentrations of UA in patients
      with lymphatic metastasis were found to be increased compared with patients
      without lymphatic metastasis (270.9 +/- 52.99 vs 215.8 +/- 43.55; P < 0.001).
      There were positive correlations of serum UA with creatinine (Cr), CRP, and CEA
      (r = 0.281, P = 0.023; r = 0.312, P = 0.001; r = 0.294, P = 0.017) in rectal
      cancer patients with metastasis. Multivariate analysis model revealed that
      elevated serum levels of UA were significant prognostic marker for lymphatic
      metastasis in patients with rectal cancer, independently of CRP, CEA, and tumor
      diameter (odds ratio 1.035, 95% CI 1.013-1.057, P = 0.002). In receiver-operating
      characteristic curve analysis, the area under the curve of serum UA in assessing
      metastatic rectal cancer patients was 0.803, with sensitivity of 0.864 and
      specificity of 0.739.Our results suggest that serum UA may be a novel marker in
      assessing tumor metastasis in patients with rectal cancer.

PMID- 27893693
TI  - Two case reports of severe myocarditis associated with the initiation of
      dolutegravir treatment in HIV patients.
AB  - RATIONALE: The integrase inhibitor dolutegravir is now recommended as first-line
      treatment for HIV. A single case of myocarditis after treatment with dolutegravir
      was reported in the FLAMINGO trial. We present here 2 cases of severe myocarditis
      that occurred shortly after the initiation of dolutegravir treatment. PATIENTS
      CONCERNS: The first case is a 45-year-old female who developed severe congestive
      heart failure and died, weeks after the initiation of dolutegravir treatment (for
      simplification of her antiretroviral regimen). The second case was a 51-year-old
      male who presented with effort dyspnea 3 weeks after the initiation of
      dolutegravir treatment and was later diagnosed as severe congestive heart
      failure. The treatment was changed and the patient survived, but he still suffers
      from severe heart failure with functional impairment. DIAGNOSIS AND OUTCOME:
      Patient 1 died, patient 2 suffers from severe heart failure. LESSONS: We discuss
      here the possible relationship between the initiation of dolutegravir treatment
      and the development of lymphocytic myocarditis in our patients, and we suggest a
      possible mechanism.

PMID- 27893694
TI  - The safety and efficacy of vitamin K antagonist in atrial fibrillation patients
      with previous ulcer bleeding: Long-term results from a multicenter study.
AB  - This study aimed to evaluate the safety and efficacy of vitamin K antagonist
      (VKA) in atrial fibrillation (AF) patients with previous ulcer bleeding.In this
      multicenter, retrospective analysis, clinical outcomes of 754 AF patients with a
      history of ulcer bleeding were evaluated. After ulcer treatment, 458 patients
      (61%) were treated with VKA, and the outcomes were compared to 296 patients (39%)
      without VKA.VKA treatment significantly increased major bleeding (7.3%/year vs
      3.2%/year, P < 0.001), and reduced major adverse cardiac events (MACE) (5.4%/year
      vs 10.0%/year, P < 0.001). Specifically, risk of gastrointestinal bleeding was
      significantly higher in the VKA group than no-VKA group (5.7%/year vs 2.6%/year,
      P < 0.001). Consequently, there was no difference in the incidence of composite
      of a MACE and major bleeding, between the 2 groups. In patients with time in the
      therapeutic range (TTR) >=65%, VKA significantly decreased MACE (2.8%/year vs
      10.0%/year, P < 0.001) without increasing major bleeding. Net clinical benefit
      model showed beneficial effects of VKA in patients with TTR >=65%, and harmful
      effects in those with TTR < 55%.In AF patients with previous ulcer bleeding, VKA
      treatment did not improve clinical outcomes unless the international normalized
      ratio level was constantly maintained (TTR >=65%), as the gastrointestinal
      bleeding (GIB) risk significantly increased.

PMID- 27893696
TI  - Molecular epidemiological study of enteroviruses associated with encephalitis in
      children from Hangzhou, China.
AB  - Enterovirus (EV) has over 100 serotypes of species A-D, which can cause various
      symptoms in infants. Enterovirus encephalitis (EVE) is serve disease with high
      morbidity and mortality in children. To well define the epidemiology of EVE, we
      wanted to know more about EV and EV molecular typing by conducting this study in
      Hangzhou.Cerebrospinal fluid samples were collected from children with diagnosis
      of encephalitis. Meanwhile, one-step real-time RT-PCR was used for the detection
      of EV, and we also identified the serotypes of EV by using gene sequencing of VP1
      or 5'UTR region.A total of 126 CSF specimens were tested and EV was detected in
      26 specimens (20.6%). The molecular typing results showed different types of EV
      strains including Coxsackievirus B2, Coxsackievirus B3, Echovirus 5, Echovirus
      16, Echovirus 18, Echovirus 30, and all EV isolates belonging to the human EV
      species B.According to the sequence of VP1 and 5'UTR region, E30 may be major
      cause of children's EVE in Hangzhou, China.

PMID- 27893695
TI  - Clinical assessment tests in evaluating patients with chronic obstructive
      pulmonary disease: A cross-sectional study.
AB  - Exertional dyspnea scales (EDS) and health-related quality-of-life questionnaires
      (HRQoLQs) are used to assess chronic obstructive pulmonary disease (COPD). The
      GOLD guidelines categorize patients according to either 1 of these 2 domains, the
      lung function and the frequency of acute exacerbations in the preceding year,
      however with inconsistent results. Combining EDS and HRQoLQs may yield better
      results; however, the best combination is unclear. Whether the EDS quantifies the
      exercise capacity or the dyspnea perception is also unclear. The study was
      designed to correlate the EDS with exercise capacity and dyspnea perception and
      to evaluate the best combination of the EDS and HRQoLQ.Three EDS were compared by
      exercise capacity and Borg scores at rest and during exercise in 57 patients with
      COPD. Three HRQoLQs were compared by 4 domains of clinical assessments, and 2
      types of exercise. The strength of correlation |r| was categorized by quartiles
      from <0.3 to >=0.6.The EDS was better correlated with exercise capacities (|r| =
      0.29-0.65, P < 0.05-<0.0001) than with the resting and exertional Borg scores
      (|r| = 0.08-0.55, P = NS- <0.0001). The EDS were moderately to strongly
      interrelated, but this correlation was weaker when including Oxygen-cost Diagram
      (OCD) (with the modified Medical Research Council, mMRC r = -0.56, with the
      baseline dyspnea index, BDI r = 0.49 vs. mMRC with BDI r = -0.73); however, the
      OCD had the strongest correlation with walking distance (r = 0.65, vs mMRC r = 
      0.59, BDI r = 0.5) and peak oxygen uptake (r = 0.39 vs mMRC r = -0.29, BDI r =
      0.36). Among the HRQoLQs, the COPD assessment test (CAT) was most strongly
      correlated with the St. George Respiratory Questionnaire (SGRQ) (r = 0.77) and
      similar to the SGRQ regarding significant correlations with the other instruments
      (|r| = 0.29-0.67 vs. 0.36-0.77) but poorly with walking distance (r = -0.02). The
      OCD was mildly correlated with the CAT (r = -0.4).The EDS was more related to the
      exercise capacity than to the dyspnea perception and the CAT was most closely
      related to the other instruments but poorly with walking distance. The OCD can be
      used to compensate for this weak correlation. The study suggests using the CAT
      and the OCD simultaneously when undertaking clinical evaluation of patients with
      COPD.

PMID- 27893697
TI  - Morbidity and mortality predictivity of nutritional assessment tools in the
      postoperative care unit.
AB  - The aim was to evaluate the nutritional situation of patients admitted to the
      Postoperative Acute Care Unit using classic methods of objective anthropometry,
      systemic evaluation methods, and Nutrition Risk in Critically Ill (NUTRIC) score,
      and to compare them as a predictor of morbidity and mortality.At admission to the
      postoperative care unit, patients undergoing various surgeries were assessed for
      the following items: Subjective Global Assessment (SGA), Nutritional Risk Index
      (NRI), Nutritional Risk Screening (NRS)-2002, Mini Nutritional Assessment (MNA),
      Charlson comorbidity index (CCI), and NUTRIC score, anthropometric measurements,
      serum total protein, serum albumin, and lymphocyte count. Patients were monitored
      for postoperative complications until death or discharge. Correlation of
      complications with these parameters was also analyzed.A total of 152 patients
      were included in the study. In this study a positive correlation was determined
      between mortality and NRS-2002, SGA, CCI, Acute Physiology and Chronic Health
      Evaluation , Sepsis-related Organ Failure Assessment, and NUTRIC score, whereas a
      negative correlation was determined between mortality and NRI. There was a
      correlation between NUTRIC score and pneumonia, development of atrial
      fibrillation, delirium, renal failure, inotrope use, and duration of mechanical
      ventilation. In our study group of postoperative patients, MNA had no predictive
      properties for any complication, whereas SGA had no predictive properties for any
      complications other than duration of hospital stay and mortality.The NUTRIC score
      is an important indicator of mortality and morbidity in postoperative surgical
      patients. NRI correlated with many postoperative complications, and though SGA
      and NRS were correlated with mortality, they were not correlated with the
      majority of complications. MNA was determined not to have any correlation with
      any complication, mortality, and duration of hospital stay in our patient group.

PMID- 27893698
TI  - Influence of Acoustic Overstimulation on the Central Auditory System: An
      Functional Magnetic Resonance Imaging (fMRI) Study.
AB  - BACKGROUND The goal of the fMRI experiment was to explore the involvement of
      central auditory structures in pathomechanisms of a behaviorally manifested
      auditory temporary threshold shift in humans. MATERIAL AND METHODS The material
      included 18 healthy volunteers with normal hearing. Subjects in the exposure
      group were presented with 15 min of binaural acoustic overstimulation of
      narrowband noise (3 kHz central frequency) at 95 dB(A). The control group was not
      exposed to noise but instead relaxed in silence. Auditory fMRI was performed in 1
      session before and 3 sessions after acoustic overstimulation and involved 3.5-4.5
      kHz sweeps. RESULTS The outcomes of the study indicate a possible effect of
      acoustic overstimulation on central processing, with decreased brain responses to
      auditory stimulation up to 20 min after exposure to noise. The effect can be seen
      already in the primary auditory cortex. Decreased BOLD signal change can be due
      to increased excitation thresholds and/or increased spontaneous activity of
      auditory neurons throughout the auditory system. CONCLUSIONS The trial shows that
      fMRI can be a valuable tool in acoustic overstimulation studies but has to be
      used with caution and considered complimentary to audiological measures. Further
      methodological improvements are needed to distinguish the effects of TTS and
      neuronal habituation to repetitive stimulation.

PMID- 27893699
TI  - Nivolumab-Induced Severe Akathisia in an Advanced Lung Cancer Patient.
AB  - BACKGROUND Nivolumab is an anti-PD-1 immune checkpoint inhibitor that was
      recently developed for cancer immunotherapy. In the clinical trials of nivolumab,
      its adverse effects were reported to be less likely than those of conventional
      anti-cancer agents; however, after practical clinical distribution, it has come
      to be known that nivolumab induces various immune-related adverse events. CASE
      REPORT A 58-year-old male with a recurrence of lung adenocarcinoma was treated
      with nivolumab. Only four days after the initial administration of nivolumab, the
      patient presented with unbearable restlessness and distress that was resistant to
      all therapeutic agents used, and it gradually became worse. He finally came to
      need deep sedation despite his cancer status being stable during the course.
      Clinical tests including magnetic resonance imaging, cerebrospinal fluid
      cytology, and antibodies of paraneoplastic syndrome exhibited no signs of
      encephalitis or another possible cause of the neuropathy. The diagnosis of
      akathisia could be made only by his somatoform presentation. It was uncertain
      whether or not this complication was correlated with the activation of his immune
      system. CONCLUSIONS Anti-immune check point inhibitors may induce many unknown
      adverse events. Severe akathisia induced by nivolumab, as in our case, has not
      been reported yet. Collecting every adverse event of nivolumab may be important
      to make a better algorithm to manage its huge variety of complications.

PMID- 27893702
TI  - Failure to detect DNA-guided genome editing using Natronobacterium gregoryi
      Argonaute.

PMID- 27893701
TI  - The signaling adaptor TRAF1 negatively regulates Toll-like receptor signaling and
      this underlies its role in rheumatic disease.
AB  - TRAF1 is a signaling adaptor known for its role in tumor necrosis factor receptor
      induced cell survival. Here we show that monocytes from healthy human subjects
      with a rheumatoid arthritis-associated single-nucleotide polymorphism (SNP) in
      the TRAF1 gene express less TRAF1 protein but greater amounts of inflammatory
      cytokines in response to lipopolysaccharide (LPS). The TRAF1 MATH domain binds
      directly to three components of the linear ubiquitination (LUBAC) complex,
      SHARPIN, HOIP and HOIL-1, to interfere with the recruitment and linear
      ubiquitination of NEMO. This results in decreased NF-kappaB activation and
      cytokine production, independently of tumor necrosis factor. Consistent with
      this, Traf1-/- mice show increased susceptibility to LPS-induced septic shock.
      These findings reveal an unexpected role for TRAF1 in negatively regulating Toll
      like receptor signaling, providing a mechanistic explanation for the increased
      inflammation seen with a disease-associated TRAF1 SNP.

PMID- 27893700
TI  - Trans-presentation of IL-6 by dendritic cells is required for the priming of
      pathogenic TH17 cells.
AB  - The cellular sources of interleukin 6 (IL-6) that are relevant for
      differentiation of the TH17 subset of helper T cells remain unclear. Here we used
      a novel strategy for the conditional deletion of distinct IL-6-producing cell
      types to show that dendritic cells (DCs) positive for the signaling regulator
      Sirpalpha were essential for the generation of pathogenic TH17 cells. Using their
      IL-6 receptor alpha-chain (IL-6Ralpha), Sirpalpha+ DCs trans-presented IL-6 to T
      cells during the process of cognate interaction. While ambient IL-6 was
      sufficient to suppress the induction of expression of the transcription factor
      Foxp3 in T cells, trans-presentation of IL-6 by DC-bound IL-6Ralpha (called 'IL-6
      cluster signaling' here) was needed to prevent premature induction of interferon
      gamma (IFN-gamma) expression in T cells and to generate pathogenic TH17 cells in
      vivo. Our findings should guide therapeutic approaches for the treatment of TH17
      cell-mediated autoimmune diseases.

PMID- 27893704
TI  - Activation and reduction of carbon dioxide by nitrogenase iron proteins.
AB  - The iron (Fe) proteins of molybdenum (Mo) and vanadium (V) nitrogenases mimic
      carbon monoxide (CO) dehydrogenase in catalyzing the interconversion between CO2
      and CO under ambient conditions. Catalytic reduction of CO2 to CO is achieved in
      vitro and in vivo upon redox changes of the Fe-protein-associated [Fe4S4]
      clusters. These observations establish the Fe protein as a model for
      investigation of CO2 activation while suggesting its biotechnological
      adaptability for recycling the greenhouse gas into useful products.

PMID- 27893703
TI  - Generation of genome-scale metabolic reconstructions for 773 members of the human
      gut microbiota.
AB  - Genome-scale metabolic models derived from human gut metagenomic data can be used
      as a framework to elucidate how microbial communities modulate human metabolism
      and health. We present AGORA (assembly of gut organisms through reconstruction
      and analysis), a resource of genome-scale metabolic reconstructions semi
      automatically generated for 773 human gut bacteria. Using this resource, we
      identified a defined growth medium for Bacteroides caccae ATCC 34185. We also
      showed that interactions among modeled species depend on both the metabolic
      potential of each species and the nutrients available. AGORA reconstructions can
      integrate either metagenomic or 16S rRNA sequencing data sets to infer the
      metabolic diversity of microbial communities. AGORA reconstructions could provide
      a starting point for the generation of high-quality, manually curated metabolic
      reconstructions. AGORA is fully compatible with Recon 2, a comprehensive
      metabolic reconstruction of human metabolism, which will facilitate studies of
      host-microbiome interactions.

PMID- 27893705
TI  - Gephyrin-binding peptides visualize postsynaptic sites and modulate
      neurotransmission.
AB  - gamma-Aminobutyric acid type A and glycine receptors are the major mediators of
      fast synaptic inhibition in the human central nervous system and are established
      drug targets. However, all drugs targeting these receptors bind to the
      extracellular ligand-binding domain of the receptors, which inherently is
      associated with perturbation of the basic physiological action. Here we pursue a
      fundamentally different approach, by instead targeting the intracellular receptor
      gephyrin interaction. First, we defined the gephyrin peptide-binding consensus
      sequence, which facilitated the development of gephyrin super-binding peptides
      and later effective affinity probes for the isolation of native gephyrin. Next,
      we demonstrated that fluorescent super-binding peptides could be used to directly
      visualize inhibitory postsynaptic sites for the first time in conventional and
      super-resolution microscopy. Finally, we demonstrate that the gephyrin super
      binding peptides act as acute intracellular modulators of fast synaptic
      inhibition by modulating receptor clustering, thus being conceptually novel
      modulators of inhibitory neurotransmission.

PMID- 27893707
TI  - Blockade of the IL-6 trans-signalling/STAT3 axis suppresses cachexia in Kras
      induced lung adenocarcinoma.
AB  - Lung cancer is the leading cause of cancer death worldwide, and is frequently
      associated with the devastating paraneoplastic syndrome of cachexia. The potent
      immunomodulatory cytokine interleukin (IL)-6 has been linked with the development
      of lung cancer as well as cachexia; however, the mechanisms by which IL-6
      promotes muscle wasting in lung cancer cachexia are ill-defined. In this study,
      we report that the gp130F/F knock-in mouse model displaying hyperactivation of
      the latent transcription factor STAT3 via the common IL-6 cytokine family
      signalling receptor, gp130, develops cachexia during Kras-driven lung
      carcinogenesis. Specifically, exacerbated weight loss, early mortality and
      reduced muscle and adipose tissue mass were features of the gp130F/F:KrasG12D
      model, but not parental KrasG12D mice in which STAT3 was not hyperactivated. Gene
      expression profiling of muscle tissue in cachectic gp130F/F:KrasG12D mice
      revealed the upregulation of IL-6 and STAT3-target genes compared with KrasG12D
      muscle tissue. These cachectic features of gp130F/F:KrasG12D mice were abrogated
      upon the genetic normalization of STAT3 activation or ablation of IL-6 in
      gp130F/F:KrasG12D:Stat3-/+ or gp130F/F:KrasG12D:Il6-/- mice, respectively.
      Furthermore, protein levels of the soluble IL-6 receptor (sIL-6R), which is the
      central facilitator of IL-6 trans-signalling, were elevated in cachectic muscle
      from gp130F/F:KrasG12D mice, and the specific blockade of IL-6 trans-signalling,
      but not classical signalling, with an anti-IL-6R antibody ameliorated cachexia
      related characteristics in gp130F/F:KrasG12D mice. Collectively, these
      preclinical findings identify trans-signalling via STAT3 as the signalling
      modality by which IL-6 promotes muscle wasting in lung cancer cachexia, and
      therefore support the clinical evaluation of the IL-6 trans-signalling/STAT3 axis
      as a therapeutic target in advanced lung cancer patients presenting with
      cachexia.

PMID- 27893706
TI  - MicroRNA-383 located in frequently deleted chromosomal locus 8p22 regulates CD44
      in prostate cancer.
AB  - A major genomic alteration in prostate cancer (PCa) is frequent loss of
      chromosome (chr) 8p with a common region of loss of heterozygosity (LOH) at
      chr8p22 locus. Genomic studies implicate this locus in the initiation of
      clinically significant PCa and with progression to metastatic disease. However,
      the genes within this region have not been fully characterized to date. Here we
      demonstrate for the first time that a microRNA component of this region-miR-383
      is frequently downregulated in prostate cancer, has a critical role in
      determining tumor-initiating potential and is involved in prostate cancer
      metastasis via direct regulation of CD44, a ubiquitous marker of PCa tumor
      initiating cells (TICs)/stem cells. Expression analyses of miR-383 in PCa
      clinical tissues established that low miR-383 expression is associated with poor
      prognosis. Functional data suggest that miR-383 regulates PCa tumor
      initiating/stem-like cells via CD44 regulation. Ectopic expression of miR-383
      inhibited tumor-initiating capacity of CD44+ PCa cells. Also, 'anti-metastatic'
      effects of ectopic miR-383 expression were observed in a PCa experimental
      metastasis model. In view of our results, we propose that frequent loss of miR
      383 at chr8p22 region leads to tumor initiation and prostate cancer metastasis.
      Thus, we have identified a novel finding that associates a long observed genomic
      alteration to PCa stemness and metastasis. Our data suggest that restoration of
      miR-383 expression may be an effective therapeutic modality against PCa.
      Importantly, we identified miR-383 as a novel PCa tissue diagnostic biomarker
      with a potential that outperforms that of serum PSA.

PMID- 27893708
TI  - TGF-beta upregulates the translation of USP15 via the PI3K/AKT pathway to promote
      p53 stability.
AB  - Crosstalk between transforming growth factor beta (TGF-beta) signaling and p53
      has a critical role in cancer progression. TGF-beta signals via Smad and non-Smad
      pathways. Under normal conditions, wild-type p53 forms a complex with Smad2/3 and
      co-activates transcription of a variety of tumor suppressor genes, resulting in
      tumor suppressive effects. Thus, p53 stability is essential in progression of
      tumor suppressive responses mediated by TGF-beta signaling. However, it remains
      unknown whether p53 stability is regulated by TGF-beta. In the current study, we
      identify that USP15 binds to and stabilizes p53 through deubiquitination in U2OS
      and HEK293 cells. TGF-beta promotes the translation of USP15 through activation
      of mammalian target of rapamycin by the phosphoinositide 3-kinase/AKT pathway.
      Upregulation of USP15 translation links the crosstalk between TGF-beta signaling
      and p53 stability, allowing this cytokine to have a critical role in cancer
      progression.

PMID- 27893709
TI  - Identification of MYST3 as a novel epigenetic activator of ERalpha frequently
      amplified in breast cancer.
AB  - Estrogen receptor alpha (ERalpha) is a master driver of a vast majority of breast
      cancers. Breast cancer cells often develop resistance to endocrine therapy via
      restoration of the ERalpha activity through survival pathways. Thus identifying
      the epigenetic activator of ERalpha that can be targeted to block ERalpha gene
      expression is a critical topic of endocrine therapy. Here, integrative genomic
      analysis identified MYST3 as a potential oncogene target that is frequently
      amplified in breast cancer. MYST3 is involved in histone acetylation via its
      histone acetyltransferase domain (HAT) and, as a result, activates gene
      expression by altering chromatin structure. We found that MYST3 was amplified in
      11% and/or overexpressed in 15% of breast tumors, and overexpression of MYST3
      correlated with worse clinical outcome in estrogen receptor+ (ER+) breast
      cancers. Interestingly, MYST3 depletion drastically inhibited proliferation in
      MYST3-high, ER+ breast cancer cells, but not in benign breast epithelial cells or
      in MYST3-low breast cancer cells. Importantly, we discovered that knocking down
      MYST3 resulted in profound reduction of ERalpha expression, while ectopic
      expression of MYST3 had the reversed effect. Chromatin immunoprecipitation
      revealed that MYST3 binds to the proximal promoter region of ERalpha gene, and
      inactivating mutations in its HAT domain abolished its ability to regulate
      ERalpha, suggesting MYST3 functioning as a histone acetyltransferase that
      activates ERalpha promoter. Furthermore, MYST3 inhibition with inducible MYST3
      shRNAs potently attenuated breast tumor growth in mice. Together, this study
      identifies the first histone acetyltransferase that activates ERalpha expression
      which may be potentially targeted to block ERalpha at transcriptional level.

PMID- 27893710
TI  - MUC1-C activates BMI1 in human cancer cells.
AB  - B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) is a
      component of the polycomb repressive complex 1 (PRC1) complex that is
      overexpressed in breast and other cancers, and promotes self-renewal of cancer
      stem-like cells. The oncogenic mucin 1 (MUC1) C-terminal (MUC1-C) subunit is
      similarly overexpressed in human carcinoma cells and has been linked to their
      self-renewal. There is no known relationship between MUC1-C and BMI1 in cancer.
      The present studies demonstrate that MUC1-C drives BMI1 transcription by a MYC
      dependent mechanism in breast and other cancer cells. In addition, we show that
      MUC1-C blocks miR-200c-mediated downregulation of BMI1 expression. The functional
      significance of this MUC1-C->?BMI1 pathway is supported by the demonstration that
      targeting MUC1-C suppresses BMI1-induced ubiquitylation of H2A and thereby
      derepresses homeobox HOXC5 and HOXC13 gene expression. Notably, our results
      further show that MUC1-C binds directly to BMI1 and promotes occupancy of BMI1 on
      the CDKN2A promoter. In concert with BMI1-induced repression of the p16INK4a
      tumor suppressor, we found that targeting MUC1-C is associated with induction of
      p16INK4a expression. In support of these results, analysis of three gene
      expresssion data sets demonstrated highly significant correlations between MUC1-C
      and BMI1 in breast cancers. These findings uncover a previously unrecognized role
      for MUC1-C in driving BMI1 expression and in directly interacting with this stem
      cell factor, linking MUC1-C with function of the PRC1 in epigenetic gene
      silencing.

PMID- 27893711
TI  - The induction of MIG6 under hypoxic conditions is critical for dormancy in
      primary cultured lung cancer cells with activating EGFR mutations.
AB  - The biologic activity of individual cancer cells is highly heterogeneous.
      Hypoxia, one of the prominent features of a tumor microenvironment, is thought to
      be causal in generating this cellular heterogeneity. In this study, we revealed
      that primary lung cancer cells harboring activating epidermal growth factor
      receptor (EGFR) mutations generally entered a dormant state when hypoxic. We
      found that heterodimer formation of the ERBB family receptor tyrosine kinases
      (RTKs), and their subsequent downstream signaling, was diminished under hypoxic
      conditions, although phosphorylation of the EGFR was retained. Dormant lung
      cancer cells were found to be resistant to EGFR tyrosine kinase inhibitor (TKI)
      treatment. In terms of mechanism, we found that a negative regulator of ERBB
      signaling, MIG6/ERRFI1/RALT/Gene33, was induced by hypoxia both in vitro and in
      vivo. MIG6 expression prevented heterodimer formation of ERBB family RTKs, and
      suppressed their downstream signaling. Knockdown of MIG6 enhanced tumor cell
      growth under hypoxic conditions, and promoted the phosphorylation of ERK and AKT
      via increased EGFR-HER3 binding. Critically, sensitivity to an EGFR-TKI, as well
      as to irradiation under hypoxic conditions, was increased in MIG6 knockdown
      cells. The expression of MIG6 was partly correlated with a pS6 negative zone in
      patient tumors. Analyses of tumor sections from 68 patients with activating EGFR
      mutations showed that patients with high MIG6 expression showed significantly
      shorter survival after EGFR-TKI treatment than other groups. Collectively, our
      data suggest that dormant cancer cells with a high MIG6 expression level might be
      one of the causes of EGFR-TKI resistance in EGFR mutant lung cancer cells.

PMID- 27893712
TI  - Blood vessel endothelium-directed tumor cell streaming in breast tumors requires
      the HGF/C-Met signaling pathway.
AB  - During metastasis to distant sites, tumor cells migrate to blood vessels. In
      vivo, breast tumor cells utilize a specialized mode of migration known as
      streaming, where a linear assembly of tumor cells migrate directionally towards
      blood vessels on fibronectin-collagen I-containing extracellular matrix (ECM)
      fibers in response to chemotactic signals. We have successfully reconstructed
      tumor cell streaming in vitro by co-plating tumors cells, macrophages and
      endothelial cells on 2.5 MUm thick ECM-coated micro-patterned substrates. We
      found that tumor cells and macrophages, when plated together on the micro
      patterned substrates, do not demonstrate sustained directional migration in only
      one direction (sustained directionality) but show random bi-directional walking.
      Sustained directionality of tumor cells as seen in vivo was established in vitro
      when beads coated with human umbilical vein endothelial cells were placed at one
      end of the micro-patterned 'ECM fibers' within the assay. We demonstrated that
      these endothelial cells supply the hepatocyte growth factor (HGF) required for
      the chemotactic gradient responsible for sustained directionality. Using this in
      vitro reconstituted streaming system, we found that directional streaming is
      dependent on, and most effectively blocked, by inhibiting the HGF/C-Met signaling
      pathway between endothelial cells and tumor cells. Key observations made with the
      in vitro reconstituted system implicating C-Met signaling were confirmed in vivo
      in mammary tumors using the in vivo invasion assay and intravital multiphoton
      imaging of tumor cell streaming. These results establish HGF/C-Met as a central
      organizing signal in blood vessel-directed tumor cell migration in vivo and
      highlight a promising role for C-Met inhibitors in blocking tumor cell streaming
      and metastasis in vivo, and for use in human trials.

PMID- 27893713
TI  - Phosphorylation of NFAT3 by CDK3 induces cell transformation and promotes tumor
      growth in skin cancer.
AB  - The nuclear factor of activated T cells (NFAT) family proteins are transcription
      factors that regulate the expression of pro-inflammatory cytokines and other
      genes during the immune response. Although the NFAT proteins have been
      extensively investigated in the immune system, their role in cancer progression
      remains controversial. Here, we report that NFAT3 is highly expressed in various
      skin cancer cell lines and tumor tissues. Knockdown of endogenous NFAT3
      expression by short hairpin RNA (shRNA) significantly inhibited tumor cell
      proliferation, colony formation and anchorage-independent cell growth.
      Furthermore, results of the mammalian two-hybrid assay showed that cyclin
      dependent kinase 3 (CDK3) directly interacted with NFAT3 and phosphorylated NFAT3
      at serine 259 (Ser259), which enhanced the transactivation and transcriptional
      activity of NFAT3. The phosphorylation site of NFAT3 was critical for epidermal
      growth factor (EGF)-stimulated cell transformation of the HaCaT immortalized skin
      cell line and mutation of NFAT3 at Ser259 led to a reduction of colony formation
      in soft agar. We also found that overexpressing wildtype NFAT3, but not mutant
      NFAT3-S259A, promoted A431 xenograft tumor growth. Importantly, we showed that
      CDK3, NFAT3 and phosphorylated NFAT3-Ser259 were highly expressed in skin cancer
      compared with normal skin tissues. These results provided evidence supporting the
      oncogenic potential of NFAT3 and suggested that CDK3-mediated phosphorylation of
      NFAT3 has an important role in skin tumorigenesis.

PMID- 27893714
TI  - The LIM protein AJUBA promotes colorectal cancer cell survival through
      suppression of JAK1/STAT1/IFIT2 network.
AB  - The LIM protein AJUBA is a scaffold protein participating in the regulation of
      cell adhesion, mitosis, DNA damage, cell differentiation, proliferation,
      migration and gene transcription. However, its roles in tumorigenesis and
      progression are poorly defined. Here, we report that AJUBA is highly expressed in
      colorectal cancer (CRC) and promotes CRC cell growth in culture and in
      xenografted mice via an inhibition of apoptosis. AJUBA represses the expression
      of IFIT2 gene, an interferon-stimulated gene and a known apoptosis inducer and
      tumour suppressor to mediate its resistance to apoptosis. Mechanistic
      investigations reveal that AJUBA specifically binds the FERM domain of JAK1 to
      dissociate JAK1 from the IFNgamma recepter, resulting in an inhibition of STAT1
      phosporylation and concomitantly its nuclear translocation. Clinically, the level
      of AJUBA in CRC specimens is negatively correlated with the levels of IFIT2 and
      pSTAT1. Collectively, these studies demonstrate that AJUBA can promote CRC growth
      via inhibiting apoptosis and serve as a target for the therapeutics and a marker
      for diagnosis of CRC.

PMID- 27893715
TI  - TGFbeta promotes mesenchymal phenotype of pancreatic cancer cells, in part,
      through epigenetic activation of VAV1.
AB  - The highly homeostasis-resistant nature of cancer cells leads to their escape
      from treatment and to liver metastasis, which in turn makes pancreatic ductal
      adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to
      mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying
      tumour heterogeneity remain elusive, we investigated whether epigenetic
      regulation might explain inter-individual differences in the progression of
      specific subtypes. DNA methylation profiling performed on cancer tissues prior to
      chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the
      VAV1 gene body that was correlated with demethylation of two promoter CpGs
      (CpG6772370/CpG6772811) in both PDAC and peripheral blood. Transforming growth
      factor beta treatment induced gene-body hypermethylation, dissociation of DNMT1
      from the promoter, and VAV1 expression via SMAD4 and mutant KrasG12D.
      Pharmacological inhibition of TGFbeta-VAV1 signalling decreased the squamous/EMT
      like cancer cells, promoted nuclear VAV1 localization, and enhanced the efficacy
      of gemcitabine in prolonging the survival of KPfl/flC mice. Together, the three
      VAV1 CpGs serve as biomarkers for prognosis and early detection, and the TGFbeta
      VAV1 axis represents a therapeutic target.

PMID- 27893716
TI  - Hic-5 remodeling of the stromal matrix promotes breast tumor progression.
AB  - The remodeling of the stromal extracellular matrix (ECM) has a crucial, but
      incompletely understood role during tumor progression and metastasis. Hic-5, a
      focal adhesion scaffold protein, has previously been implicated in tumor cell
      invasion, proliferation and metastasis. To investigate the role of Hic-5 in
      breast tumor progression in vivo, Hic-5-/- mice were generated and crossed with
      the Mouse Mammary Tumor Virus-Polyoma Middle T-Antigen mouse. Tumors from the Hic
      5-/-;PyMT mice exhibited increased latency and reduced growth, with fewer lung
      metastases, as compared with Hic-5+/-;PyMT mice. Immunohistochemical analysis
      showed that Hic-5 is primarily expressed in the cancer-associated fibroblasts
      (CAFs). Further analysis revealed that the Hic-5-/-;PyMT tumor stroma contains
      fewer CAFs and exhibits reduced ECM deposition. The remodeling of the stromal
      matrix by CAFs has been shown to increase tumor rigidity to indirectly regulate
      FAK Y397 phosphorylation in tumor cells to promote their growth and invasion.
      Accordingly, the Hic-5-/-;PyMT tumor cells exhibited a reduction in FAK Y397
      phosphorylation. Isolated Hic-5-/-;PyMT CAFs were defective in stress fiber
      organization and exhibited reduced contractility. These cells also failed to
      efficiently deposit and organize the ECM in two and three dimensions. This, in
      turn, impacted three-dimensional MDA-MB-231 tumor cell migration behavior. Thus,
      using a new knockout mouse model, we have identified Hic-5 expression in CAFs as
      a key requirement for deposition and remodeling of the stromal ECM to promote non
      cell autonomous breast tumor progression.

PMID- 27893718
TI  - FOXO3 is essential for CD44 expression in pancreatic cancer cells.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of cancer
      and the 5-year survival rate is only 5%. Several studies have suggested that
      cancer stem cells (CSCs) are thought to be involved in recurrence and metastasis
      and so it is essential to establish an approach targeting CSCs. Here we have
      demonstrated that cyclic guanosine monophosphate (cGMP) suppressed CD44
      expression and the properties of CSCs in PDAC. Microarray analysis suggested that
      cGMP inhibited Forkhead box O3 (FOXO3), which is known as a tumor suppressor.
      Surprisingly, our data demonstrated that FOXO3 is essential for CD44 expression
      and the properties of CSCs. Our data also indicated that patients with high FOXO3
      activation signatures had poor prognoses. This evidence suggested that cGMP
      induction and FOXO3 inhibition could be ideal candidates for pancreatic CSC.

PMID- 27893717
TI  - Androgen and AR contribute to breast cancer development and metastasis: an
      insight of mechanisms.
AB  - The role of androgen and androgen receptor (AR) in breast carcinogenesis has long
      been a disputed issue. This report provides a mechanistic insight into how
      androgen and AR contributes to invasion and metastasis of breast cancer. We find
      that dihydrotestosterone (DHT) is able to induce the epithelial-to-mesenchymal
      transition in breast cancer cells in an AR-dependent/estrogen receptor
      independent manner. This process is dependent on the demethylation activity of
      lysine-specific demethylase 1A (LSD1) by epigenetically regulating the target
      genes E-cadherin and vimentin. In vivo, DHT promotes metastasis in a nude mouse
      model, and AR and LSD1 are indispensable in this process. We establish that
      higher expression of nucleus AR to cytoplasm AR associated with worse prognostic
      outcomes in breast cancer patient samples. This study maps an 'androgen-AR/LSD1
      target genes' pathway in breast carcinogenesis, implicating the importance of
      hormonal balance in women, and the potential clinical significance of serum
      androgen and AR in prediction of breast cancer and selection of breast cancer
      therapy.

PMID- 27893719
TI  - Novel KDM1A inhibitors induce differentiation and apoptosis of glioma stem cells
      via unfolded protein response pathway.
AB  - Glioma stem cells (GSCs) have a central role in glioblastoma (GBM) development
      and chemo/radiation resistance, and their elimination is critical for the
      development of efficient therapeutic strategies. Recently, we showed that lysine
      demethylase KDM1A is overexpressed in GBM. In the present study, we determined
      whether KDM1A modulates GSCs stemness and differentiation and tested the utility
      of two novel KDM1A-specific inhibitors (NCL-1 and NCD-38) to promote
      differentiation and apoptosis of GSCs. The efficacy of KDM1A targeting drugs was
      tested on purified GSCs isolated from established and patient-derived GBMs using
      both in vitro assays and in vivo orthotopic preclinical models. Our results
      suggested that KDM1A is highly expressed in GSCs and knockdown of KDM1A using
      shRNA-reduced GSCs stemness and induced the differentiation. Pharmacological
      inhibition of KDM1A using NCL-1 and NCD-38 significantly reduced the cell
      viability, neurosphere formation and induced apoptosis of GSCs with little effect
      on differentiated cells. In preclinical studies using orthotopic models, NCL-1
      and NCD-38 significantly reduced GSCs-driven tumor progression and improved mice
      survival. RNA-sequencing analysis showed that KDM1A inhibitors modulate several
      pathways related to stemness, differentiation and apoptosis. Mechanistic studies
      showed that KDM1A inhibitors induce activation of the unfolded protein response
      (UPR) pathway. These results strongly suggest that selective targeting of KDM1A
      using NCL-1 and NCD-38 is a promising therapeutic strategy for elimination of
      GSCs.

PMID- 27893723
TI  - Slip-activated surface creep with room-temperature super-elongation in metallic
      nanocrystals.
AB  - Nanoscale metallic crystals have been shown to follow a 'smaller is stronger'
      trend. However, they usually suffer from low ductility due to premature plastic
      instability by source-limited crystal slip. Here, by performing in situ atomic
      scale transmission electron microscopy, we report unusual room-temperature super
      elongation without softening in face-centred-cubic silver nanocrystals, where
      crystal slip serves as a stimulus to surface diffusional creep. This interplay
      mechanism is shown experimentally and theoretically to govern the plastic
      deformation of nanocrystals over a material-dependent sample diameter range
      between the lower and upper limits for nanocrystal stability by surface
      diffusional creep and dislocation plasticity, respectively, which extends far
      beyond the maximum size for pure diffusion-mediated deformation (for example,
      Coble-type creep). This work provides insight into the atomic-scale coupled
      diffusive-displacive deformation mechanisms, maximizing ductility and strength
      simultaneously in nanoscale materials.

PMID- 27893721
TI  - Biomarkers associated with bronchopulmonary dysplasia/mortality in premature
      infants.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) portends lifelong organ impairment
      and death. Our ability to predict BPD in first days of life is limited, but could
      be enhanced using novel biomarkers. METHODS: Using an available clinical and
      urine biomarker database obtained from a prospective 113 infant cohort (birth
      weight <=1,200 g and/or gestational age <=31 wk), we evaluated the independent
      association of 14 urine biomarkers with BPD/mortality. RESULTS: Two of the 14
      urine biomarkers were independently associated with BPD/mortality after
      controlling for gestational age (GA), small for gestational age (SGA), and
      intubation status. The best performing protein was clusterin, a ubiquitously
      expressed protein and potential sensor of oxidative stress associated with lung
      function in asthma patients. When modeling for BPD/mortality, the independent
      odds ratio for maximum adjusted urine clusterin was 9.2 (95% CI: 3.3-32.8, P <
      0.0001). In this model, clinical variables (GA, intubation status, and SGA)
      explained 38.3% of variance; clusterin explained an additional 9.2%, while
      albumin explained an additional 3.4%. The area under the curve incorporating
      clinical factors and biomarkers was 0.941. CONCLUSION: Urine clusterin and
      albumin may improve our ability to predict BPD/mortality. Future studies are
      needed to validate these findings and determine their clinical usefulness.

PMID- 27893722
TI  - Valley photonic crystals for control of spin and topology.
AB  - Photonic crystals offer unprecedented opportunity for light manipulation and
      applications in optical communication and sensing. Exploration of topology in
      photonic crystals and metamaterials with non-zero gauge field has inspired a
      number of intriguing optical phenomena such as one-way transport and Weyl points.
      Recently, a new degree of freedom, valley, has been demonstrated in two
      dimensional materials. Here, we propose a concept of valley photonic crystals
      with electromagnetic duality symmetry but broken inversion symmetry. We observe
      photonic valley Hall effect originating from valley-dependent spin-split bulk
      bands, even in topologically trivial photonic crystals. Valley-spin locking
      behaviour results in selective net spin flow inside bulk valley photonic
      crystals. We also show the independent control of valley and topology in a single
      system that has been long pursued in electronic systems, resulting in
      topologically-protected flat edge states. Valley photonic crystals not only offer
      a route towards the observation of non-trivial states, but also open the way for
      device applications in integrated photonics and information processing using spin
      dependent transportation.

PMID- 27893720
TI  - A functional ATG16L1 (T300A) variant is associated with necrotizing enterocolitis
      in premature infants.
AB  - BACKGROUND: The genetic basis of dysfunctional immune responses in necrotizing
      enterocolitis (NEC) remains unknown. We hypothesized that variants in nucleotide
      binding and oligomerization domain (NOD)-like receptors (NLRs) and autophagy
      (ATG) genes modulate vulnerability to NEC. METHODS: We genotyped a multi-center
      cohort of premature infants with and without NEC for NOD1, NOD2, ATG16L1, CARD8,
      and NLRP3 variants. Chi-square tests and logistic regression were used for
      statistical analysis. RESULTS: In our primary cohort (n = 1,015), 86 (8.5%)
      infants developed NEC. The A allele of the ATG16L1 (Thr300Ala) variant was
      associated with increased NEC (AA vs. AG vs. GG; 11.3 vs. 8.4 vs. 4.8%, P =
      0.009). In regression models for NEC that adjusted for epidemiological
      confounders, GA (P = 0.033) and the AA genotype (P = 0.038) of ATG16L1 variant
      were associated with NEC. The association between the A allele of the ATG16L1
      variant and NEC remained significant among Caucasian infants (P = 0.02). In a
      replication cohort (n = 259), NEC rates were highest among infants with the AA
      genotype but did not reach statistical significance. CONCLUSION: We report a
      novel association between a hypomorphic variant in an autophagy gene (ATG16L1)
      and NEC in premature infants. Our data suggest that decreased autophagy arising
      from genetic variants may confer protection against NEC.

PMID- 27893725
TI  - Biredox ionic liquids with solid-like redox density in the liquid state for high
      energy supercapacitors.
AB  - Kinetics of electrochemical reactions are several orders of magnitude slower in
      solids than in liquids as a result of the much lower ion diffusivity. Yet, the
      solid state maximizes the density of redox species, which is at least two orders
      of magnitude lower in liquids because of solubility limitations. With regard to
      electrochemical energy storage devices, this leads to high-energy batteries with
      limited power and high-power supercapacitors with a well-known energy deficiency.
      For such devices the ideal system should endow the liquid state with a density of
      redox species close to the solid state. Here we report an approach based on
      biredox ionic liquids to achieve bulk-like redox density at liquid-like fast
      kinetics. The cation and anion of these biredox ionic liquids bear moieties that
      undergo very fast reversible redox reactions. As a first demonstration of their
      potential for high-capacity/high-rate charge storage, we used them in redox
      supercapacitors. These ionic liquids are able to decouple charge storage from an
      ion-accessible electrode surface, by storing significant charge in the pores of
      the electrodes, to minimize self-discharge and leakage current as a result of
      retaining the redox species in the pores, and to raise working voltage due to
      their wide electrochemical window.

PMID- 27893724
TI  - Polaritons in layered two-dimensional materials.
AB  - In recent years, enhanced light-matter interactions through a plethora of dipole
      type polaritonic excitations have been observed in two-dimensional (2D) layered
      materials. In graphene, electrically tunable and highly confined plasmon
      polaritons were predicted and observed, opening up opportunities for
      optoelectronics, bio-sensing and other mid-infrared applications. In hexagonal
      boron nitride, low-loss infrared-active phonon-polaritons exhibit hyperbolic
      behaviour for some frequencies, allowing for ray-like propagation exhibiting high
      quality factors and hyperlensing effects. In transition metal dichalcogenides,
      reduced screening in the 2D limit leads to optically prominent excitons with
      large binding energy, with these polaritonic modes having been recently observed
      with scanning near-field optical microscopy. Here, we review recent progress in
      state-of-the-art experiments, and survey the vast library of polaritonic modes in
      2D materials, their optical spectral properties, figures of merit and application
      space. Taken together, the emerging field of 2D material polaritonics and their
      hybrids provide enticing avenues for manipulating light-matter interactions
      across the visible, infrared to terahertz spectral ranges, with new optical
      control beyond what can be achieved using traditional bulk materials.

PMID- 27893728
TI  - DNA origami tiles: Nanoscale mazes.

PMID- 27893726
TI  - Glutamatergic synaptic integration of locomotion speed via septoentorhinal
      projections.
AB  - The medial septum and diagonal band of Broca (MSDB) send glutamatergic axons to
      medial entorhinal cortex (MEC). We found that this pathway provides speed
      correlated input to several MEC cell-types in layer 2/3. The speed signal is
      integrated most effectively by pyramidal cells but also excites stellate cells
      and interneurons. Thus, the MSDB conveys speed information that can be used by
      MEC neurons for spatial representation of self-location.

PMID- 27893727
TI  - Mechanosensory hair cells express two molecularly distinct mechanotransduction
      channels.
AB  - Auditory hair cells contain mechanotransduction channels that rapidly open in
      response to sound-induced vibrations. We report here that auditory hair cells
      contain two molecularly distinct mechanotransduction channels. One ion channel is
      activated by sound and is responsible for sensory transduction. This sensory
      transduction channel is expressed in hair cell stereocilia, and previous studies
      show that its activity is affected by mutations in the genes encoding the
      transmembrane proteins TMHS, TMIE, TMC1 and TMC2. We show here that the second
      ion channel is expressed at the apical surface of hair cells and that it contains
      the Piezo2 protein. The activity of the Piezo2-dependent channel is controlled by
      the intracellular Ca2+ concentration and can be recorded following disruption of
      the sensory transduction machinery or more generally by disruption of the sensory
      epithelium. We thus conclude that hair cells express two molecularly and
      functionally distinct mechanotransduction channels with different subcellular
      distributions.

PMID- 27893729
TI  - Programmable disorder in random DNA tilings.
AB  - Scaling up the complexity and diversity of synthetic molecular structures will
      require strategies that exploit the inherent stochasticity of molecular systems
      in a controlled fashion. Here we demonstrate a framework for programming random
      DNA tilings and show how to control the properties of global patterns through
      simple, local rules. We constructed three general forms of planar network-random
      loops, mazes and trees-on the surface of self-assembled DNA origami arrays on the
      micrometre scale with nanometre resolution. Using simple molecular building
      blocks and robust experimental conditions, we demonstrate control of a wide range
      of properties of the random networks, including the branching rules, the growth
      directions, the proximity between adjacent networks and the size distribution.
      Much as combinatorial approaches for generating random one-dimensional chains of
      polymers have been used to revolutionize chemical synthesis and the selection of
      functional nucleic acids, our strategy extends these principles to random two
      dimensional networks of molecules and creates new opportunities for fabricating
      more complex molecular devices that are organized by DNA nanostructures.

PMID- 27893731
TI  - Observation of extreme phase transition temperatures of water confined inside
      isolated carbon nanotubes.
AB  - Fluid phase transitions inside single, isolated carbon nanotubes are predicted to
      deviate substantially from classical thermodynamics. This behaviour enables the
      study of ice nanotubes and the exploration of their potential applications. Here
      we report measurements of the phase boundaries of water confined within six
      isolated carbon nanotubes of different diameters (1.05, 1.06, 1.15, 1.24, 1.44
      and 1.52 nm) using Raman spectroscopy. The results reveal an exquisite
      sensitivity to diameter and substantially larger temperature elevations of the
      freezing transition (by as much as 100  degrees C) than have been theoretically
      predicted. Dynamic water filling and reversible freezing transitions were marked
      by 2-5 cm-1 shifts in the radial breathing mode frequency, revealing reversible
      melting bracketed to 105-151  degrees C and 87-117  degrees C for 1.05 and 1.06
      nm single-walled carbon nanotubes, respectively. Near-ambient phase changes were
      observed for 1.44 and 1.52 nm nanotubes, bracketed between 15-49  degrees C and 3
      30  degrees C, respectively, whereas the depression of the freezing point was
      observed for the 1.15 nm nanotube between -35 and 10  degrees C. We also find
      that the interior aqueous phase reversibly decreases the axial thermal
      conductivity of the nanotube by as much as 500%, allowing digital control of the
      heat flux.

PMID- 27893732
TI  - Multiple nanostructures based on anodized aluminium oxide templates.
AB  - Several physico-chemical effects and properties in the solid state involve
      nanoscale interactions between adjacent materials and morphologies. Arrays of
      binary nanostructures can generate intimate interactions between different sub
      components, but fabricating binary nanostructures is challenging. Here, we
      propose a concept to achieve diverse binary nanostructure arrays with high
      degrees of controllability for each of the sub-components, including material,
      dimension and morphology. This binary nanostructuring concept originates with a
      distinctive binary-pore anodized aluminium oxide template that includes two
      dissimilar sets of pores in one matrix, where the openings of the two sets of
      pores are towards opposite sides of the template. Using the same growth
      mechanism, the binary-pore template can be extended to multi-pore templates with
      more geometrical options. We also present photoelectrodes, transistors and
      plasmonic devices made with our binary nanostructure arrays using different
      combination of materials and morphologies, and demonstrate superior performances
      compared to their single-component counterparts.

PMID- 27893730
TI  - Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities
      induced by brain-disease-related genetic risk factors.
AB  - Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the
      world population) involve a large network of genes displaying subtle changes in
      their expression. Abnormalities in intraneuronal transport have been linked to
      genetic risk factors found in patients, suggesting the relevance of measuring
      this key biological process. However, current techniques are not sensitive enough
      to detect minor abnormalities. Here we report a sensitive method to measure the
      changes in intraneuronal transport induced by brain-disease-related genetic risk
      factors using fluorescent nanodiamonds (FNDs). We show that the high brightness,
      photostability and absence of cytotoxicity allow FNDs to be tracked inside the
      branches of dissociated neurons with a spatial resolution of 12 nm and a temporal
      resolution of 50 ms. As proof of principle, we applied the FND tracking assay on
      two transgenic mouse lines that mimic the slight changes in protein concentration
      (~30%) found in the brains of patients. In both cases, we show that the FND assay
      is sufficiently sensitive to detect these changes.

PMID- 27893733
TI  - ADARB1 catalyzes circadian A-to-I editing and regulates RNA rhythm.
AB  - It has been proposed that the CLOCK-ARNTL (BMAL1) complex drives circadian
      transcription of thousands of genes, including Per and Cry family genes that
      encode suppressors of CLOCK-ARNTL-dependent transcription. However, recent
      studies demonstrated that 70-80% of circadian-oscillating mRNAs have no obvious
      rhythms in their de novo transcription, indicating the potential importance of
      post-transcriptional regulation. Our CLOCK-ChIP-seq analysis identified rhythmic
      expression of adenosine deaminase, RNA-specific, B1 (Adarb1, also known as
      Adar2), an adenosine-to-inosine (A-to-I) RNA-editing enzyme. RNA-seq showed
      circadian rhythms of ADARB1-mediated A-to-I editing in a variety of transcripts.
      In Adarb1-knockout mice, rhythms of large populations of mRNA were attenuated,
      indicating a profound impact of ADARB1-mediated A-to-I editing on RNA rhythms.
      Furthermore, Adarb1-knockout mice exhibited short-period rhythms in locomotor
      activity and gene expression. These phenotypes were associated with abnormal
      accumulation of CRY2. The present study identifies A-to-I RNA editing as a key
      mechanism of post-transcriptional regulation in the circadian clockwork.

PMID- 27893734
TI  - An iPSC-derived vascular model of Marfan syndrome identifies key mediators of
      smooth muscle cell death.
AB  - Marfan syndrome (MFS) is a heritable connective tissue disorder caused by
      mutations in FBN1, which encodes the extracellular matrix protein fibrillin-1. To
      investigate the pathogenesis of aortic aneurysms in MFS, we generated a vascular
      model derived from human induced pluripotent stem cells (MFS-hiPSCs). Our MFS
      hiPSC-derived smooth muscle cells (SMCs) recapitulated the pathology seen in
      Marfan aortas, including defects in fibrillin-1 accumulation, extracellular
      matrix degradation, transforming growth factor-beta (TGF-beta) signaling,
      contraction and apoptosis; abnormalities were corrected by CRISPR-based editing
      of the FBN1 mutation. TGF-beta inhibition rescued abnormalities in fibrillin-1
      accumulation and matrix metalloproteinase expression. However, only the
      noncanonical p38 pathway regulated SMC apoptosis, a pathological mechanism also
      governed by Kruppel-like factor 4 (KLF4). This model has enabled us to dissect
      the molecular mechanisms of MFS, identify novel targets for treatment (such as
      p38 and KLF4) and provided an innovative human platform for the testing of new
      drugs.

PMID- 27893735
TI  - Computational Discovery of Putative Leads for Drug Repositioning through Drug
      Target Interaction Prediction.
AB  - De novo experimental drug discovery is an expensive and time-consuming task. It
      requires the identification of drug-target interactions (DTIs) towards targets of
      biological interest, either to inhibit or enhance a specific molecular function.
      Dedicated computational models for protein simulation and DTI prediction are
      crucial for speed and to reduce the costs associated with DTI identification. In
      this paper we present a computational pipeline that enables the discovery of
      putative leads for drug repositioning that can be applied to any microbial
      proteome, as long as the interactome of interest is at least partially known.
      Network metrics calculated for the interactome of the bacterial organism of
      interest were used to identify putative drug-targets. Then, a random forest
      classification model for DTI prediction was constructed using known DTI data from
      publicly available databases, resulting in an area under the ROC curve of 0.91
      for classification of out-of-sampling data. A drug-target network was created by
      combining 3,081 unique ligands and the expected ten best drug targets. This
      network was used to predict new DTIs and to calculate the probability of the
      positive class, allowing the scoring of the predicted instances. Molecular
      docking experiments were performed on the best scoring DTI pairs and the results
      were compared with those of the same ligands with their original targets. The
      results obtained suggest that the proposed pipeline can be used in the
      identification of new leads for drug repositioning. The proposed classification
      model is available at http://bioinformatics.ua.pt/software/dtipred/.

PMID- 27893737
TI  - Long-Range Memory in Literary Texts: On the Universal Clustering of the Rare
      Words.
AB  - A fundamental problem in linguistics is how literary texts can be quantified
      mathematically. It is well known that the frequency of a (rare) word in a text is
      roughly inverse proportional to its rank (Zipf's law). Here we address the
      complementary question, if also the rhythm of the text, characterized by the
      arrangement of the rare words in the text, can be quantified mathematically in a
      similar basic way. To this end, we consider representative classic single
      authored texts from England/Ireland, France, Germany, China, and Japan. In each
      text, we classify each word by its rank. We focus on the rare words with ranks
      above some threshold Q and study the lengths of the (return) intervals between
      them. We find that for all texts considered, the probability SQ(r) that the
      length of an interval exceeds r, follows a perfect Weibull-function, SQ(r) = exp(
      b(beta)rbeta), with beta around 0.7. The return intervals themselves are arranged
      in a long-range correlated self-similar fashion, where the autocorrelation
      function CQ(s) of the intervals follows a power law, CQ(s) ~ s-gamma, with an
      exponent gamma between 0.14 and 0.48. We show that these features lead to a
      pronounced clustering of the rare words in the text.

PMID- 27893739
TI  - Evaluating Carbonate System Algorithms in a Nearshore System: Does Total
      Alkalinity Matter?
AB  - Ocean acidification is a threat to many marine organisms, especially those that
      use calcium carbonate to form their shells and skeletons. The ability to
      accurately measure the carbonate system is the first step in characterizing the
      drivers behind this threat. Due to logistical realities, regular carbonate system
      sampling is not possible in many nearshore ocean habitats, particularly in
      remote, difficult-to-access locations. The ability to autonomously measure the
      carbonate system in situ relieves many of the logistical challenges; however, it
      is not always possible to measure the two required carbonate parameters
      autonomously. Observed relationships between sea surface salinity and total
      alkalinity can frequently provide a second carbonate parameter thus allowing for
      the calculation of the entire carbonate system. Here, we assessed the rigor of
      estimating total alkalinity from salinity at a depth <15 m by routinely sampling
      water from a pier in southern California for several carbonate system parameters.
      Carbonate system parameters based on measured values were compared with those
      based on estimated TA values. Total alkalinity was not predictable from salinity
      or from a combination of salinity and temperature at this site. However,
      dissolved inorganic carbon and the calcium carbonate saturation state of these
      nearshore surface waters could both be estimated within on average 5% of measured
      values using measured pH and salinity-derived or regionally averaged total
      alkalinity. Thus we find that the autonomous measurement of pH and salinity can
      be used to monitor trends in coastal changes in DIC and saturation state and be a
      useful method for high-frequency, long-term monitoring of ocean acidification.

PMID- 27893738
TI  - Fenugreek Seed Powder Nullified Aluminium Chloride Induced Memory Loss,
      Biochemical Changes, Abeta Burden and Apoptosis via Regulating Akt/GSK3beta
      Signaling Pathway.
AB  - Alzheimer's disease (AD) is the most common form of dementia that mainly affects
      the cognitive functions of the aged populations. Trigonella foenum-graecum (L.)
      (fenugreek), a traditionally well utilized medicinal plant ubiquitously used as
      one of the main food additive worldwide, is known to have numerous beneficial
      health effects. Fenugreek seed extract could be able to inhibit the activity of
      acetylcholinesterase (AChE), a key enzyme involved in the pathogenesis of AD, and
      further shown to have anti-parkinsonic effect. The present study was aimed to
      explore the neuroprotective effect of fenugreek seed powder (FSP) against
      aluminium chloride (AlCl3) induced experimental AD model. Administration of
      germinated FSP (2.5, 5 and 10% mixed with ground standard rat feed) protected
      AlCl3 induced memory and learning impairments, Al overload, AChE hyperactivity,
      amyloid beta (Abeta) burden and apoptosis via activating Akt/GSK3beta pathway.
      Our present data could confirm the neuroprotective effect of fenugreek seeds.
      Further these results could lead a possible therapeutics for the management of
      neurodegenerative diseases including AD in future.

PMID- 27893740
TI  - Low CO2 Sensitivity of Microzooplankton Communities in the Gullmar Fjord,
      Skagerrak: Evidence from a Long-Term Mesocosm Study.
AB  - Ocean acidification is considered as a crucial stressor for marine communities.
      In this study, we tested the effects of the IPCC RPC6.0 end-of-century
      acidification scenario on a natural plankton community in the Gullmar Fjord,
      Sweden, during a long-term mesocosm experiment from a spring bloom to a mid
      summer situation. The focus of this study was on microzooplankton and its
      interactions with phytoplankton and mesozooplankton. The microzooplankton
      community was dominated by ciliates, especially small Strombidium sp., with the
      exception of the last days when heterotrophic dinoflagellates increased in
      abundance. We did not observe any effects of high CO2 on the community
      composition and diversity of microzooplankton. While ciliate abundance, biomass
      and growth rate were not affected by elevated CO2, we observed a positive effect
      of elevated CO2 on dinoflagellate abundances. Additionally, growth rates of
      dinoflagellates were significantly higher in the high CO2 treatments. Given the
      higher Chlorophyll a content measured under high CO2, our results point at mainly
      indirect effects of CO2 on microzooplankton caused by changes in phytoplankton
      standing stocks, in this case most likely an increase in small-sized
      phytoplankton of <8 MUm. Overall, the results from the present study covering the
      most important part of the growing season indicate that coastal microzooplankton
      communities are rather robust towards realistic acidification scenarios.

PMID- 27893736
TI  - Diet-Induced Nutritional Stress and Pathogen Interference in Wolbachia-Infected
      Aedes aegypti.
AB  - The pathogen interference phenotype greatly restricts infection with dengue virus
      (DENV) and other pathogens in Wolbachia-infected Aedes aegypti, and is a vital
      component of Wolbachia-based mosquito control. Critically, the phenotype's causal
      mechanism is complex and poorly understood, with recent evidence suggesting that
      the cause may be species specific. To better understand this important phenotype,
      we investigated the role of diet-induced nutritional stress on interference
      against DENV and the avian malarial parasite Plasmodium gallinaceum in Wolbachia
      infected Ae. aegypti, and on physiological processes linked to the phenotype.
      Wolbachia-infected mosquitoes were fed one of four different concentrations of
      sucrose, and then challenged with either P. gallinaceum or DENV. Interference
      against P. gallinaceum was significantly weakened by the change in diet however
      there was no effect on DENV interference. Immune gene expression and H2O2 levels
      have previously been linked to pathogen interference. These traits were assayed
      for mosquitoes on each diet using RT-qPCR and the Amplex Red Hydrogen
      Peroxide/Peroxidase Assay Kit, and it was observed that the change in diet did
      not significantly affect immune expression, but low carbohydrate levels led to a
      loss of ROS induction in Wolbachia-infected mosquitoes. Our data suggest that
      host nutrition may not influence DENV interference for Wolbachia-infected
      mosquitoes, but Plasmodium interference may be linked to both nutrition and
      oxidative stress. This pathogen-specific response to nutritional change
      highlights the complex nature of interactions between Wolbachia and pathogens in
      mosquitoes.

PMID- 27893741
TI  - Downregulation of Blood Monocyte HLA-DR in ICU Patients Is Also Present in Bone
      Marrow Cells.
AB  - BACKGROUND: The downregulation of blood monocyte HLA-DR expression also occurs in
      tissue infiltrative cells in a context of acute clinical inflammation, especially
      sepsis. This context favors the development of secondary infections and results
      from various mechanisms. Little is known about HLA-DR expression on bone marrow
      (BM) cells of the monocyte lineage, the source of circulating monocytes. This
      study analyzed the BM HLA-DR expression in ICU patients compared to BM monocytes
      from non-ICU patients and to blood monocytes of control healthy donors. A
      potential dysfunction of myeloid differentiation was investigated in a sub
      population of these ICU patients to characterize the phenotype of the immature
      forms of monocytes and granulocytes in BM. METHODS AND FINDINGS: BM and blood
      were drawn from 33 ICU and 9 non-ICU patients having a BM analysis to precise the
      etiology of abnormal low count in blood cells. The data were compared with blood
      cells of 28 control donors. Flow cytometry was used for both HLA-DR expression
      and phenotyping of immature forms of monocytes and granulocytes. HLA-DR
      expression was downregulated in both blood and BM monocyte in ICU patients
      compared to BM of non-ICU patients and blood of control donors. Amplitude of HLA
      DR downregulation was comparable in septic and non-septic ICU patients. The
      phenotype of immature forms of monocytes and granulocytes in BM (n = 11) did not
      show abnormal myeloid (monocyte + granulocyte) differentiation. CONCLUSION: The
      downregulation of HLA-DR in BM monocyte lineage is present in ICU patients
      without major changes in myeloid cells. It may result from a regulation mediated
      by soluble and/or neuro-endocrine factors present in BM cell microenvironment.

PMID- 27893742
TI  - Maintenance of Taste Organs Is Strictly Dependent on Epithelial Hedgehog/GLI
      Signaling.
AB  - For homeostasis, lingual taste papilla organs require regulation of epithelial
      cell survival and renewal, with sustained innervation and stromal interactions.
      To investigate a role for Hedgehog/GLI signaling in adult taste organs we used a
      panel of conditional mouse models to manipulate GLI activity within epithelial
      cells of the fungiform and circumvallate papillae. Hedgehog signaling suppression
      rapidly led to taste bud loss, papilla disruption, and decreased proliferation in
      domains of papilla epithelium that contribute to taste cells. Hedgehog responding
      cells were eliminated from the epithelium but retained in the papilla stromal
      core. Despite papilla disruption and loss of taste buds that are a major source
      of Hedgehog ligand, innervation to taste papillae was maintained, and not
      misdirected, even after prolonged GLI blockade. Further, vimentin-positive
      fibroblasts remained in the papilla core. However, retained innervation and
      stromal cells were not sufficient to maintain taste bud cells in the context of
      compromised epithelial Hedgehog signaling. Importantly taste organ disruption
      after GLI blockade was reversible in papillae that retained some taste bud cell
      remnants where reactivation of Hedgehog signaling led to regeneration of papilla
      epithelium and taste buds. Therefore, taste bud progenitors were either retained
      during epithelial GLI blockade or readily repopulated during recovery, and were
      poised to regenerate taste buds once Hedgehog signaling was restored, with
      innervation and papilla connective tissue elements in place. Our data argue that
      Hedgehog signaling is essential for adult tongue tissue maintenance and that
      taste papilla epithelial cells represent the key targets for physiologic Hedgehog
      dependent regulation of taste organ homeostasis. Because disruption of GLI
      transcriptional activity in taste papilla epithelium is sufficient to drive taste
      organ loss, similar to pharmacologic Hedgehog pathway inhibition, the findings
      suggest that taste alterations in cancer patients using systemic Hedgehog pathway
      inhibitors result principally from interruption of signaling activity in taste
      papillae.

PMID- 27893743
TI  - Trends of Bacterial Keratitis Culture Isolates in Jerusalem; a 13- Years
      Analysis.
AB  - PURPOSE: To describe the trends in pathogens and antibacterial resistance of
      corneal culture isolates in infectious keratitis during a period of 13 years at
      Hadassah-Hebrew University Medical Center. METHODS: A Retrospective analysis of
      bacterial corneal isolates was performed during the months of January 2002 to
      December 2014 at Hadassah Hebrew University Medical Center. Demographics,
      microbiological data and antibiotic resistance and sensitivity were collected.
      RESULTS: A total of 943 corneal isolates were analyzed during a 13 year period. A
      total of 415 positive bacterial cultures and 37 positive fungal cultures were
      recovered, representing 48% of the total cultures. The Annual incidence was 34.78
      +/- 6.54 cases. The most common isolate was coagulase-negative staphylococcus
      (32%), which had a significant decrease in trend throughout the study period (APC
      = -8.1, p = 0.002). Methicillin-resistant Staphylococcus aureus (MRSA) appears to
      have a decrease trend (APC = -31.2, P = 0.5). There was an increase in the
      resistance trend of coagulase-negative staphylococci to penicillin (APC = 5.0, P
      = <0.001). None of the pathogens had developed any resistance to Vancomycin. (P =
      0.88). CONCLUSIONS: Coagulase negative staphylococci were the predominant
      bacteria isolated from patients with keratitis. There was no significant change
      in the annual incidence of cases of bacterial keratitis seen over the past 13
      years. Keratitis caused by MRSA appeared to decrease in contrast to the reported
      literature.

PMID- 27893744
TI  - Optimization of Irreversible Electroporation Protocols for In-vivo Myocardial
      Decellularization.
AB  - BACKGROUND: Irreversible electroporation (IRE) is a non-thermal cell ablation
      approach that induces selective damage to cell membranes only. The purpose of the
      current study was to evaluate and optimize its use for in-vivo myocardial
      decellularization. METHODS: Forty-two Sprague-Dawley rats were used to compare
      myocardial damage of seven different IRE protocols with anterior myocardial
      infarction damage. An in-vivo open thoracotomy model was used, with two-needle
      electrodes in the anterior ventricular wall. IRE protocols included different
      combinations of pulse lengths (70 vs. 100 MUseconds), frequency (1, 2, 4 Hz), and
      number (10 vs. 20 pulses), as well as voltage intensity (50, 250 and 500 Volts).
      All animals underwent baseline echocardiographic evaluation. Degree of myocardial
      ablation was determined using repeated echocardiography measurements (days 7 and
      28) as well as histologic and morphometric analysis at 28 days. RESULTS: All
      animals survived 28 days of follow-up. Compared with 50V and 250V,
      electroporation with 500V was associated with significantly increased myocardial
      scar and reduction in ejection fraction (67.4%+/-4% at baseline vs. 34.6%+/-20%
      at 28 days; p <0.01). Also, compared with pulse duration of 70 MUsec, pulses of
      100 MUsec were associated with markedly reduced left ventricular function and
      markedly increased relative scar area ratio (28%+/-9% vs. 16%+/-3%, p = 0.02).
      Decreasing electroporation pulse frequency (1Hz vs. 2Hz, 2Hz vs. 4Hz) was
      associated with a significant increase in myocardial damage. Electroporation
      protocols with a greater number of pulses (20 vs. 10) correlated with more
      profound tissue damage (p<0.05). When compared with myocardial infarction damage,
      electroporation demonstrated a considerable likeness regarding the extent of the
      inflammatory process, but with relatively higher levels of extra-cellular
      preservation. CONCLUSIONS: IRE has a graded effect on the myocardium. The extent
      of ablation can be controlled by changing pulse length, frequency and number, as
      well as by changing electric field intensity.

PMID- 27893745
TI  - Public Stigma against People with Mental Illness in Jimma Town, Southwest
      Ethiopia.
AB  - BACKGROUND: Stigma towards people with mental illness (PWMI) can result in low
      self-esteem and isolation and threaten employment. Therefore, this study aimed to
      assess the magnitude of public stigma against PWMI and factors associated with it
      among Jimma town residents. METHODS: A community-based, cross-sectional,
      descriptive study was conducted in adult residents of Jimma town. Data were
      collected among 820 randomly selected residents with the interviewer-administered
      Community Attitudes toward the Mentally Ill (CAMI) scale. Linear regression
      analyses were performed to identify predictors of stigma against PWMI. RESULT: A
      total of 444 (54%) of the 820 respondents were females, and the mean (SD) age was
      35 (8.5) years. The minimum and maximum possible values on each CAMI subscale
      were 10 and 50, respectively. The respondents had high scores for a stigmatizing
      attitude towards PWMI across all the subscales, as indicated by the mean (SD)
      scores: authoritarianism, 27.17 (4.96); social restrictiveness, 32.41 (4.20);
      benevolence, 35.34 (4.42); and community-based mental health ideology, 33.95
      (5.82). Compared to housewives, private organization employees showed more
      autocratic and socially restrictive views (std. beta = 1.12, P<0.01). Single
      people had a lower social restrictiveness stigma score than married people (std.
      beta = -0.20, P<0.001), and participants' academic levels correlated inversely
      with the stigma score (std. beta = -0.12, P<0.001). A higher benevolence stigma
      score was observed among participants with no relationship with PWMI than among
      those with PWMI in their neighborhood (std. beta = 0.08, P< 0.046). CONCLUSION:
      The study revealed that a negative attitude towards PWMI is widespread.
      Therefore, there is a need to develop strategies to fight the stigma attached to
      PWMI at the community level.

PMID- 27893746
TI  - Mast Cells Are Abundant in Primary Cutaneous T-Cell Lymphomas: Results from a
      Computer-Aided Quantitative Immunohistological Study.
AB  - BACKGROUND: Mast cells (MC) are bone marrow derived haematopoetic cells playing a
      crucial role not only in immune response but also in the tumor microenvironment
      with protumorigenic and antitumorigenic functions. The role of MC in primary
      cutaneous T-cell lymphomas (CTCL), a heterogeneous group of non-Hodgkin lymphomas
      with initial presentation in the skin, is largely unknown. OBJECTIVE: To gain
      more accurate information about presence, number, distribution and state of
      activation (degranulated vs. non-degranulated) of MC in CTCL variants and
      clinical stages. MATERIALS AND METHODS: We established a novel computer-aided
      tissue analysis method on digitized skin sections. Immunohistochemistry with an
      anti-MC tryptase antibody was performed on 34 biopsies of different CTCL subtypes
      and on control skin samples. An algorithm for the automatic detection of the
      epidermis and of cell density based CTCL areas was developed. Cells were
      stratified as being within the CTCL infiltrate, in P1 (a surrounding area 0-30
      MUm away from CTCL), or in P2 (30-60 MUm away from CTCL) area. RESULTS: We found
      high MC counts within CTCL infiltrates and P1 and a decreased MC number in the
      surrounding dermis P2. Higher MC numbers were found in MF compared to all other
      CTCL subgroups. Regarding different stages of MF, we found significantly higher
      mast cell counts in stages IA and IB than in stages IIA and IIB. Regarding MC
      densities, we found a higher density of MC in MF compared to all other CTCL
      subgroups. More MC were non-degranulated than degranulated. CONCLUSION: Here for
      the first time an automated method for MC analysis on tissue sections and its use
      in CTCL is described. Eliminating error from investigator bias, the method allows
      for precise cell identification and counting. Our results provide new insights on
      MC distribution in CTCL reappraising their role in the pathophysiology of CTCL.

PMID- 27893748
TI  - Communication with Family and Friends across the Life Course.
AB  - Each stage of the human life course is characterised by a distinctive pattern of
      social relations. We study how the intensity and importance of the closest social
      contacts vary across the life course, using a large database of mobile
      communication from a European country. We first determine the most likely social
      relationship type from these mobile phone records by relating the age and gender
      of the caller and recipient to the frequency, length, and direction of calls. We
      then show how communication patterns between parents and children, romantic
      partner, and friends vary across the six main stages of the adult family life
      course. Young adulthood is dominated by a gradual shift of call activity from
      parents to close friends, and then to a romantic partner, culminating in the
      period of early family formation during which the focus is on the romantic
      partner. During middle adulthood call patterns suggest a high dependence on the
      parents of the ego, who, presumably often provide alloparental care, while at
      this stage female same-gender friendship also peaks. During post-reproductive
      adulthood, individuals and especially women balance close social contacts among
      three generations. The age of grandparenthood brings the children entering
      adulthood and family formation into the focus, and is associated with a
      realignment of close social contacts especially among women, while the old age is
      dominated by dependence on their children.

PMID- 27893747
TI  - Analysis of the Function of Apoptosis during Imaginal Wing Disc Regeneration in
      Drosophila melanogaster.
AB  - Regeneration is the ability that allows organisms to replace missing organs or
      lost tissue after injuries. This ability requires the coordinated activity of
      different cellular processes, including programmed cell death. Apoptosis plays a
      key role as a source of signals necessary for regeneration in different
      organisms. The imaginal discs of Drosophila melanogaster provide a particularly
      well-characterised model system for studying the cellular and molecular
      mechanisms underlying regeneration. Although it has been shown that signals
      produced by apoptotic cells are needed for homeostasis and regeneration of some
      tissues of this organism, such as the adult midgut, the contribution of apoptosis
      to disc regeneration remains unclear. Using a new method for studying disc
      regeneration in physiological conditions, we have defined the pattern of cell
      death in regenerating discs. Our data indicate that during disc regeneration,
      cell death increases first at the wound edge, but as regeneration progresses dead
      cells can be observed in regions far away from the site of damage. This result
      indicates that apoptotic signals initiated in the wound spread throughout the
      disc. We also present results which suggest that the partial inhibition of
      apoptosis does not have a major effect on disc regeneration. Finally, our results
      suggest that during disc regeneration distinct apoptotic signals might be acting
      simultaneously.

PMID- 27893750
TI  - Molecular Epidemiology of Agents of Human Chromoblastomycosis in Brazil with the
      Description of Two Novel Species.
AB  - The human mutilating disease chromoblastomycosis is caused by melanized members
      of the order Chaetothyriales. To assess population diversity among 123 clinical
      strains of agents of the disease in Brazil we applied sequencing of the rDNA
      internal transcribed spacer region, and partial cell division cycle and beta
      tubulin genes. Strains studied were limited to three clusters divided over the
      single family Herpotrichiellaceae known to comprise agents of the disease. A
      Fonsecaea cluster contained the most important agents, among which F. pedrosoi
      was prevalent with 80% of the total set of strains, followed by 13% for F.
      monophora, 3% for F. nubica, and a single isolate of F. pugnacius. Additional
      agents, among which two novel species, were located among members of the genus
      Rhinocladiella and Cyphellophora, with frequencies of 3% and 1%, respectively.

PMID- 27893749
TI  - Differential Protein Expression in the Hemolymph of Bithynia siamensis
      goniomphalos Infected with Opisthorchis viverrini.
AB  - Bithynia siamensis goniomphalos is a freshwater snail that serves as the first
      intermediate host of the human liver fluke Opisthorchis viverrini. This parasite
      is a major public health problem in different countries throughout the Greater
      Mekong sub-region (Thailand, southern Vietnam, Lao PDR and Cambodia). Chronic O.
      viverrini infection also results in a gradual increase of fibrotic tissues in the
      biliary tract that are associated with hepatobiliary diseases and contribute to
      cholangiocarcinoma (a fatal type of bile duct cancer). Infectivity of the
      parasite in the snail host is strongly correlated with destruction of helminths
      by the snail's innate immune system, composed of cellular (hemocyte) and humoral
      (plasma) defense factors. To better understand this important host-parasite
      interface we applied sequential window acquisition of all theoretical spectra
      mass spectrometry (SWATH-MS) to identify and quantify the proteins from the
      hemolymph of B. siamensis goniomphalos experimentally infected with O. viverrini
      and compare them to non-infected snails (control group). A total of 362 and 242
      proteins were identified in the hemocytes and plasma, respectively. Of these, 145
      and 117 proteins exhibited significant differences in expression upon fluke
      infection in hemocytes and plasma, respectively. Among the proteins with
      significantly different expression patterns, we found proteins related to immune
      response (up-regulated in both hemocyte and plasma of infected snails) and
      proteins belonging to the structural and motor group (mostly down-regulated in
      hemocytes but up-regulated in plasma of infected snails). The proteins identified
      and quantified in this work will provide important information for the
      understanding of the factors involved in snail defense against O. viverrini and
      might facilitate the development of new strategies to control O. viverrini
      infection in endemic areas.

PMID- 27893751
TI  - 25-Hydroxy- and 1alpha,25-Dihydroxycholecalciferol Have Greater Potencies than 25
      Hydroxy- and 1alpha,25-Dihydroxyergocalciferol in Modulating Cultured Human and
      Mouse Osteoblast Activities.
AB  - Despite differences in the phamacokinetics of 25-hydroxycholecalciferol
      (25(OH)D3) and 25-hydroxyergocalciferol (25(OH)D2) in man, the effects of these
      and their 1alpha-hydroxylated forms (1,25(OH)2D3 and 1,25(OH)2D2) on cellular
      activity of vitamin D-responsive cells have hardly been compared. We studied
      differences in the effects of these metabolites on cell number, gene
      transcription, protein expression and mineralisation of cultured human bone
      marrow-derived stromal cells (hBMSC) and rapidly mineralising mouse 2T3
      osteoblasts. 50-1000 nM 25(OH) and 0.05-10 nM 1,25(OH)2 metabolites were used. At
      high concentrations, 25(OH)D2/D3 and 1,25(OH)2D2/D3 suppressed cell number in
      both human and mouse cells. The suppression was greater with cholecalciferol (D3)
      metabolites than with those of ergocalciferol (D2). In both cell types, 25(OH)D2
      and 25(OH)D3 increased the expression of osteopontin, osteocalcin, collagen-1,
      receptor activator of nuclear factor kappa-B ligand, vitamin D receptor, CYP24A1
      and CYP27B1 genes. Whereas there was little or no difference between the effects
      of 25(OH)D2 and 25(OH)D3 in hBMSCs, differences were observed in the magnitude of
      the effects of these metabolites on the expression of most studied genes in 2T3
      cells. Alkaline phosphatase (ALP) activity was increased by 25(OH)D2/D3 and
      1,25(OH)2D2/D3 in hBMSC and 2T3 cells, and the increase was greater with the D3
      metabolites at high concentrations. In hBMSCs, mineralisation was also increased
      by 25(OH)D2/D3 and 1,25(OH)2D2/D3 at high concentrations, with D3 metabolites
      exerting a greater influence. In 2T3 cells, the effects of these compounds on
      mineralisation were stimulatory at low concentrations and inhibitory when high
      concentrations were used. The suppression at high concentrations was greater with
      the D3 metabolites. These findings suggest that there are differences in the
      effects of 25-hydroxy and 1alpha,25(OH)2 metabolites of D3 and D2 on human
      preosteoblasts and mouse osteoblasts, with the D3 metabolites being more potent
      in suppressing cell number, increasing ALP activity and influencing
      mineralisation.

PMID- 27893753
TI  - Correction: Rare Functional Variant in TM2D3 is Associated with Late-Onset
      Alzheimer's Disease.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1006327.].

PMID- 27893752
TI  - Effect of Butyrate on Collagen Expression, Cell Viability, Cell Cycle Progression
      and Related Proteins Expression of MG-63 Osteoblastic Cells.
AB  - AIMS: Butyric acid is one major metabolic product generated by anaerobic Gram
      negative bacteria of periodontal and root canal infection. Butyric acid affects
      the activity of periodontal cells such as osteoblasts. The purposes of this study
      were to investigate the effects of butyrate on MG-63 osteoblasts. METHODS: MG-63
      cells were exposed to butyrate and cell viability was estimated by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mRNA and
      protein expression of type I collagen and cell cycle-related proteins were
      measured by reverse-transcriptase polymerase chain reaction (RT-PCR), western
      blotting or immunofluorescent staining. Cellular production of reactive oxygen
      species (ROS) was analyzed by 2',7'-dichlorofluorescein (DCF) fluorescence flow
      cytometry. RESULTS: Exposure to butyrate suppressed cell proliferation, and
      induced G2/M (8 and 16 mM) cell cycle arrest of MG-63 cells. Some cell apoptosis
      was noted. The mRNA expression of cdc2 and cyclin-B1 decreased after exposure to
      butyrate. The protein expression of type I collagen, cdc2 and cyclin B1 were
      decreased, whereas the expression of p21, p27 and p57 was stimulated. Under the
      treatment of butyrate, ROS production in MG-63 cells markedly increased.
      CONCLUSIONS: The secretion of butyric acid by periodontal and root canal
      microorganisms may inhibit bone cell growth and matrix turnover. This is possibly
      due to induction of cell cycle arrest and ROS generation and inhibition of
      collagen expression. These results suggest the involvement of butyric acid in the
      pathogenesis of periodontal and periapical tissue destruction by impairing bone
      healing responses.

PMID- 27893754
TI  - Cyp26 Enzymes Facilitate Second Heart Field Progenitor Addition and Maintenance
      of Ventricular Integrity.
AB  - Although retinoic acid (RA) teratogenicity has been investigated for decades, the
      mechanisms underlying RA-induced outflow tract (OFT) malformations are not
      understood. Here, we show zebrafish embryos deficient for Cyp26a1 and Cyp26c1
      enzymes, which promote RA degradation, have OFT defects resulting from two
      mechanisms: first, a failure of second heart field (SHF) progenitors to join the
      OFT, instead contributing to the pharyngeal arch arteries (PAAs), and second, a
      loss of first heart field (FHF) ventricular cardiomyocytes due to disrupted cell
      polarity and extrusion from the heart tube. Molecularly, excess RA signaling
      negatively regulates fibroblast growth factor 8a (fgf8a) expression and
      positively regulates matrix metalloproteinase 9 (mmp9) expression. Although
      restoring Fibroblast growth factor (FGF) signaling can partially rescue SHF
      addition in Cyp26 deficient embryos, attenuating matrix metalloproteinase (MMP)
      function can rescue both ventricular SHF addition and FHF integrity. These novel
      findings indicate a primary effect of RA-induced OFT defects is disruption of the
      extracellular environment, which compromises both SHF recruitment and FHF
      ventricular integrity.

PMID- 27893755
TI  - Quantification of Arachidonic Acid and Its Metabolites in Rat Tissues by UHPLC
      MS/MS: Application for the Identification of Potential Biomarkers of Benign
      Prostatic Hyperplasia.
AB  - To evaluate the potential relationship between benign prostatic hyperplasia (BPH)
      and the arachidonic acid (AA) metabolome, a UHPLC-MS/MS method has been developed
      and validated for simultaneous determination of AA and its cyclooxygenase(COX)
      and lipoxygenase(LOX) pathway metabolites (15-HETE, 12-HETE, TXA2, 5-HETE, AA,
      PGI2, PGF2alpha, 8-HETE, PGD2, PGE2 and LTB4) in rat tissues. The analytes were
      extracted from tissue samples with a protein precipitation procedure and then
      separated on a Shim-pack XR-ODSC18 column with 0.05% formic acid in water (pH
      adjusted with dilute ammonia) and methanol:acetonitrile (20:80, v/v). Detection
      was performed on a UHPLC-MS/MS system with electrospray negative ionization (ESI)
      and a multiple reaction-monitoring mode. The lower limits of quantification
      (LLOQ) were 0.25-50 ng/mL for all of the analytes in the prostate, seminal,
      bladder, liver and kidney tissues. The absolute recoveries of the analytes from
      all of the tissues were more than 50%. By means of the method developed, the AA
      metabolites in tissue samples from Sham and BPH group rats were determined. The
      eleven biomarkers in the BPH group prostate, seminal, bladder, liver and kidney
      tissues were significantly higher than those of the sham group, indicating that
      BPH fortified the inducible expression of COX and LOX, as well as increased the
      production of AA and eicosanoids. The method described here offers a useful tool
      for the evaluation of complex regulatory eicosanoids responses in vivo.

PMID- 27893756
TI  - Posttraumatic Stress among Not-Exposed Traumatically Bereaved Relatives after the
      MS Estonia Disaster.
AB  - BACKGROUND: Little is known about posttraumatic stress (PTS) reactions in
      bereaved individuals following loss in disaster who were not directly exposed to
      disaster. The aim of the present study was to examine the course of PTS up to
      three years after losing relatives in the MS Estonia ferry disaster, one of the
      worst maritime disasters in modern times. METHODS: Seven postal surveys were sent
      out over three years post-disaster. The respondents were invited and added
      consecutively during the three years and 938 relatives participated in one or
      more of the surveys, representing 89% of the MS Estonia's Swedish victims. The
      survey included the Impact of Event Scale (IES) to measure PTS. Latent growth
      curve modeling was used to analyze PTS over time. RESULTS: The majority of
      bereaved individuals had high levels of PTS. At three years post-loss, 62% of the
      respondents scored above the recommended cut-off value on the IES. Over time, PTS
      symptoms declined, but initially high symptoms of PTS were associated with a
      slower recovery rate. CONCLUSION: The present finding suggests that being an
      indirectly-exposed disaster-bereaved close-relative can lead to very high levels
      of PTS which are sustained for several years.

PMID- 27893757
TI  - Assessing the Acetabular Cup Implant Primary Stability by Impact Analyses: A
      Cadaveric Study.
AB  - BACKGROUND: The primary stability of the acetabular cup (AC) implant is an
      important determinant for the long term success of cementless hip surgery.
      However, it remains difficult to assess the AC implant stability due to the
      complex nature of the bone-implant interface. A compromise should be found when
      inserting the AC implant in order to obtain a sufficient implant stability
      without risking bone fracture. The aim of this study is to evaluate the potential
      of impact signals analyses to assess the primary stability of AC implants
      inserted in cadaveric specimens. METHODS: AC implants with various sizes were
      inserted in 12 cadaveric hips following the same protocol as the one employed in
      the clinic, leading to 86 different configurations. A hammer instrumented with a
      piezoelectric force sensor was then used to measure the variation of the force as
      a function of time produced during the impact between the hammer and the
      ancillary. Then, an indicator I was determined for each impact based on the
      impact momentum. For each configuration, twelve impacts were realized with the
      hammer, the value of the maximum amplitude being comprised between 2500 and 4500
      N, which allows to determine an averaged value IM of the indicator for each
      configuration. The pull-out force F was measured using a tangential pull-out
      biomechanical test. RESULTS: A significant correlation (R2 = 0.69) was found
      between IM and F when pooling all data, which indicates that information related
      to the AC implant biomechanical stability can be retrieved from the analysis of
      impact signals obtained in cadavers. CONCLUSION: These results open new paths in
      the development of a medical device that could be used in the future in the
      operative room to help orthopedic surgeons adapt the surgical protocol in a
      patient specific manner.

PMID- 27893758
TI  - Multiple Browsers Structure Tree Recruitment in Logged Temperate Forests.
AB  - Historical extirpations have resulted in depauperate large herbivore assemblages
      in many northern forests. In eastern North America, most forests are inhabited by
      a single wild ungulate species, white-tailed deer (Odocoileus virginianus), and
      relationships between deer densities and impacts on forest regeneration are
      correspondingly well documented. Recent recolonizations by moose (Alces
      americanus) in northeastern regions complicate established deer density
      thresholds and predictions of browsing impacts on forest dynamics because size
      and foraging differences between the two animals suggest a lack of functional
      redundancy. We asked to what extent low densities of deer + moose would structure
      forest communities differently from that of low densities of deer in recently
      logged patch cuts of Massachusetts, USA. In each site, a randomized block with
      three treatment levels of large herbivores-no-ungulates (full exclosure), deer
      (partial exclosure), and deer + moose (control) was established. After 6-7 years,
      deer + moose reduced stem densities and basal area by 2-3-fold, Prunus
      pensylvanica and Quercus spp. recruitment by 3-6 fold, and species richness by
      1.7 species (19%). In contrast, in the partial exclosures, deer had non
      significant effects on stem density, basal area, and species composition, but
      significantly reduced species richness by 2.5 species on average (28%). Deer
      browsing in the partial exclosure was more selective than deer + moose browsing
      together, perhaps contributing to the decline in species richness in the former
      treatment and the lack of additional decline in the latter. Moose used the
      control plots at roughly the same frequency as deer (as determined by remote
      camera traps), suggesting that the much larger moose was the dominant browser
      species in terms of animal biomass in these cuts. A lack of functional redundancy
      with respect to foraging behavior between sympatric large herbivores may explain
      combined browsing effects that were both large and complex.

PMID- 27893759
TI  - The Condition for Generous Trust.
AB  - Trust has been considered the "cement" of a society and is much studied in
      sociology and other social sciences. Most studies, however, have neglected one
      important aspect of trust: it involves an act of forgiving and showing tolerance
      toward another's failure. In this study, we refer to this concept as "generous
      trust" and examine the conditions under which generous trust becomes a more
      viable option when compared to other types of trust. We investigate two settings.
      First, we introduce two types of uncertainties: uncertainty as to whether
      trustees have the intention to cooperate, and uncertainty as to whether trustees
      have enough competence to accomplish the entrusted tasks. Second, we examine the
      manner in which trust functions in a broader social context, one that involves
      matching and commitment processes. Since we expect generosity or forgiveness to
      work differently in the matching and commitment processes, we must differentiate
      trust strategies into generous trust in the matching process and that in the
      commitment process. Our analytical strategy is two-fold. First, we analyze the
      "modified" trust game that incorporates the two types of uncertainties without
      the matching process. This simplified setting enables us to derive mathematical
      results using game theory, thereby giving basic insight into the trust mechanism.
      Second, we investigate socially embedded trust relationships in contexts
      involving the matching and commitment processes, using agent-based simulation.
      Results show that uncertainty about partner's intention and competence makes
      generous trust a viable option. In contrast, too much uncertainty undermines the
      possibility of generous trust. Furthermore, a strategy that is too generous
      cannot stand alone. Generosity should be accompanied with moderate punishment. As
      for socially embedded trust relationships, generosity functions differently in
      the matching process versus the commitment process. Indeed, these two types of
      generous trust coexist, and their coexistence enables a society to function well.

PMID- 27893761
TI  - High Accuracy Human Activity Recognition Based on Sparse Locality Preserving
      Projections.
AB  - Human activity recognition(HAR) from the temporal streams of sensory data has
      been applied to many fields, such as healthcare services, intelligent
      environments and cyber security. However, the classification accuracy of most
      existed methods is not enough in some applications, especially for healthcare
      services. In order to improving accuracy, it is necessary to develop a novel
      method which will take full account of the intrinsic sequential characteristics
      for time-series sensory data. Moreover, each human activity may has correlated
      feature relationship at different levels. Therefore, in this paper, we propose a
      three-stage continuous hidden Markov model (TSCHMM) approach to recognize human
      activities. The proposed method contains coarse, fine and accurate
      classification. The feature reduction is an important step in classification
      processing. In this paper, sparse locality preserving projections (SpLPP) is
      exploited to determine the optimal feature subsets for accurate classification of
      the stationary-activity data. It can extract more discriminative activities
      features from the sensor data compared with locality preserving projections.
      Furthermore, all of the gyro-based features are used for accurate classification
      of the moving data. Compared with other methods, our method uses significantly
      less number of features, and the over-all accuracy has been obviously improved.

PMID- 27893760
TI  - Leaf Extract from Lithocarpus polystachyus Rehd. Promote Glycogen Synthesis in
      T2DM Mice.
AB  - The purpose of this study was to investigate the effects of leaf extract from
      Lithocarpus polystachyus Rehd. on type II diabetes mellitus (T2DM) and the active
      ingredients of this effect. In addition, this study determined, for the first
      time, the underlying molecular and pharmacological mechanisms of the extracts on
      hyperglycemia using long-term double high diet-fed and streptozotocin (STZ)
      induced type II diabetic mice. In the present study, leaf extract, phloridzin and
      trilobatin were assessed in vivo (gavage) and in vitro (non-invasive micro-test
      technique, NMT) in experimental T2DM mice. The biochemical parameters were
      measured including blood glucose and blood lipid level, liver biochemical
      indexes, and hepatic glycogen. The relative expression of glycometabolism-related
      genes was detected. The effect of leaf extracts on physiological glucose flux in
      liver tissue from control and T2DM mice was also investigated. Body weight of
      experimental T2DM mice increased significantly after the first week, but
      stabilized over the subsequent three weeks; body weight of all other groups did
      not change during the four weeks' study. After four weeks, all treatment groups
      decreased blood glucose, and treatment with leaf extract had numerous positive
      effects: a) promoted in glucose uptake in liver, b) increased synthesis of liver
      glycogen, c) reduced oxidative stress, d) up-regulation of glucokinase (GK),
      glucose transporter 2 (GLUT2), insulin receptor (IR) and insulin receptor
      substrate (IRS) expression in liver, e) down-regulation of glucose-6-phosphatase
      (G-6-P) expression, and f) ameliorated blood lipid levels. Both treatment with
      trilobatin or phloridzin accelerated liver glycogen synthesis, decreased
      oxidative stress and increased expression of GK. IRS and phosphoenolpyruvate
      carboxykinase (PEPCK) were both up-regulated after treatment with trilobatin.
      Expression of GLUT2, PEPCK and G-6-P were also increased in liver tissue after
      treatment with phloridzin. Our data indicate that leaf extract from L.
      polystachyus Rehd. has a preferable hypoglycemic effects than trilobatin or
      phloridzin alone. Leaf extract significantly increased glucose uptake and hepatic
      glycogen synthesis while also inducing a decline of hepatic gluconeogenesis and
      oxidative stress in T2DM mice. From this study, we draw conclusions that L.
      polystachyus promoted glycogen synthesis in T2DM mice, and that the active
      compounds were not only the trilobatin or phloridzin.

PMID- 27893762
TI  - Circulating Angiopoietin-2 and Its Soluble Receptor Tie-2 Concentrations Are
      Related to Renal Function in Two Population-Based Cohorts.
AB  - BACKGROUND: An intact angiopoietin/Tie-2 ligand receptor system is indispensable
      for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly
      associated with kidney disease involving the progressive loss of glomerular
      filtration. The aim of our study was to investigate the associations between
      renal function and serum Ang-2 or serum Tie-2 concentrations in the general
      population. METHODS: Data of 3081 and 4088 subjects from two population-based
      studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used.
      Renal function was assessed by serum creatinine, cystatin C concentration,
      creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C
      based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses
      of variance and linear regression models were calculated. RESULTS: In both
      cohorts, strong positive associations between serum cystatin C concentrations and
      serum Ang-2 or Tie-2 concentrations as well as inverse associations between
      eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations
      were also present in a subpopulation without hypertension or diabetes mellitus
      type 2. Furthermore, we detected weak U-shaped associations between serum
      creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With
      respect to uACR a strong positive association with serum Ang-2 concentrations was
      revealed. CONCLUSION: Serum Ang-2 concentrations are strongly associated with
      sensitive parameters of renal impairment like serum cystatin C, uACR and
      eGFR(cys). These findings persisted even after exclusion of subjects with
      hypertension or diabetes mellitus type 2, conditions that predispose to chronic
      renal disease and are associated with increased Ang-2 concentrations.
      Interestingly, we did not detect the same strong relations between serum
      creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally,
      significant association of serum Tie-2 concentrations with cystatin C and
      eGFR(cys) were detected.

PMID- 27893763
TI  - The Role of Morbid Obesity in the Promotion of Metabolic Disruptions and Non
      Alcoholic Steatohepatitis by Helicobacter Pylori.
AB  - BACKGROUND: Helicobacter pylory (HP) infection has been associated to an
      increased rate of type 2 diabetes (T2D) and liver disease through its effect on
      insulin resistance and systemic inflammation. However, results are inconstant and
      no studies exist in morbidly obese patients, in which both insulin resistance and
      inflammation coexist. MATERIAL AND METHODS: Cross-sectional study to evaluate the
      relationship between HP infection and alterations in carbohydrate metabolism,
      lipid profile, inflammation markers, and liver disease in patients awaiting for
      bariatric surgery. HP infection was histologically assessed in gastric antrum
      biopsy from 416 subjects. Liver biopsy was also available in 93 subjects.
      RESULTS: Both impaired fasting glucose and T2D were similar when comparing
      subjects with and without HP infection (24.2% vs. 22%, p = 0.290 and 29.4% vs.
      29.1%, p = 0.916, respectively), with no differences between groups in the HOMA
      IR, lipid profile neither inflammatory parameters. However, HP infection was
      higher among subjects with a BMI >= 40.0 kg/m2 in comparison with lower degrees
      of obesity (71.7% vs. 60.0%, p = 0.041). In addition, subjects without HP
      infection showed higher degrees of steatosis (44.1+/-26.4% vs. 32.0+/-20.7%, p =
      0.038), as well as a lower prevalence of non-alcoholic steatohepatitis (9.3% vs.
      30.7%, p = 0.023). CONCLUSIONS: In patients with morbid obesity, HP infection
      does not seem to be associated with abnormal carbohydrate metabolism. In
      addition, less advanced degrees of non-alcoholic fatty disease were observed. We
      suggest that low-grade inflammation that accompanies obesity mitigates the
      diabetogenic effect of HP, so the presence of obesity should be considered in
      studies that evaluate the HP metabolic effects.

PMID- 27893764
TI  - Virus-Mediated Alterations in miRNA Factors and Degradation of Viral miRNAs by
      MCPIP1.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's
      sarcoma, encodes 25 mature viral miRNAs. MCP-1-induced protein-1 (MCPIP1), a
      critical regulator of immune homeostasis, has been shown to suppress miRNA
      biosynthesis via cleavage of precursor miRNAs through its RNase domain. We
      demonstrate that MCPIP1 can directly cleave KSHV and EBV precursor miRNAs and
      that MCPIP1 expression is repressed following de novo KSHV infection. In
      addition, repression with siRNAs to MCPIP1 in KSHV-infected cells increased IL-6
      and KSHV miRNA expression, supporting a role for MCPIP1 in IL-6 and KSHV miRNA
      regulation. We also provide evidence that KSHV miRNAs repress MCPIP1 expression
      by targeting the 3'UTR of MCPIP1. Conversely, expression of essential miRNA
      biogenesis components Dicer and TRBP is increased following latent KSHV
      infection. We propose that KSHV infection inhibits a negative regulator of miRNA
      biogenesis (MCPIP1) and up-regulates critical miRNA processing components to
      evade host mechanisms that inhibit expression of viral miRNAs. KSHV-mediated
      alterations in miRNA biogenesis represent a novel mechanism by which KSHV
      interacts with its host and a new mechanism for the regulation of viral miRNA
      expression.

PMID- 27893765
TI  - Improving Standards of Care in Obstructed Labour: A Criteria-Based Audit at a
      Referral Hospital in a Low-Resource Setting in Tanzania.
AB  - OBJECTIVE: In low-resource settings, obstructed labour is strongly associated
      with severe maternal morbidity and intrapartum asphyxia, and consequently
      maternal and perinatal deaths. This study evaluated the impact of a criteria
      based audit of the diagnosis and management of obstructed labour in a low
      resource setting. METHODS: A baseline criteria-based audit was conducted from
      October 2013 to March 2014, followed by a workshop in which stakeholders gave
      feedback on interventions agreed upon to improve obstetric care. The implemented
      interventions included but were not limited to introducing standard guidelines
      for diagnosis and management of obstructed labour, agreeing on mandatory review
      by specialist for cases that are assigned caesarean section, re-training and
      supervision on use and interpretation of partograph and, strengthening team work
      between doctors, mid-wives and theatre staff. After implementing these
      interventions in March, a re-audit was performed from July 2015 to November,
      2015, and the results were compared to those of the baseline audit. RESULTS: Two
      hundred and sixty deliveries in the baseline survey and 250 deliveries in the
      follow-up survey were audited. Implementing the new criteria improved the
      diagnosis from 74% to 81% (p = 0.049) and also the management of obstructed
      labour from 4.2% at baseline audit to 9.2% at re-audit (p = 0.025). Improved
      detection of prolonged labour through heightened observation of regular
      contractions, protracted cervical dilatation, protracted descent of presenting
      part, arrested cervical dilation, and severe moulding contributed to improved
      standards of diagnosis (all p < 0.04). Patient reviews by senior obstetricians
      increased from 34% to 43% (p = 0.045) and reduced time for caesarean section
      intervention from the median time of 120 to 90 minutes (p = 0.001) improved
      management (all p < 0.05). Perinatal outcomes, neonatal distress and fresh
      stillbirths, were reduced from 16% to. 8.8% (p = 0.01). CONCLUSION: A criteria
      based audit proved to be a feasible and useful tool in improving diagnosis and
      management of obstructed labour using available resources. Some of the observed
      changes in practice were of modest magnitude implying demand for further
      improvements, while sustaining those already put in place.

PMID- 27893766
TI  - The Effect of Binaural Beats on Visuospatial Working Memory and Cortical
      Connectivity.
AB  - Binaural beats utilize a phenomenon that occurs within the cortex when two
      different frequencies are presented separately to each ear. This procedure
      produces a third phantom binaural beat, whose frequency is equal to the
      difference of the two presented tones and which can be manipulated for non
      invasive brain stimulation. The effects of binaural beats on working memory, the
      system in control of temporary retention and online organization of thoughts for
      successful goal directed behavior, have not been well studied. Furthermore, no
      studies have evaluated the effects of binaural beats on brain connectivity during
      working memory tasks. In this study, we determined the effects of different
      acoustic stimulation conditions on participant response accuracy and cortical
      network topology, as measured by EEG recordings, during a visuospatial working
      memory task. Three acoustic stimulation control conditions and three binaural
      beat stimulation conditions were used: None, Pure Tone, Classical Music, 5Hz
      binaural beats, 10Hz binaural beats, and 15Hz binaural beats. We found that
      listening to 15Hz binaural beats during a visuospatial working memory task not
      only increased the response accuracy, but also modified the strengths of the
      cortical networks during the task. The three auditory control conditions and the
      5Hz and 10Hz binaural beats all decreased accuracy. Based on graphical network
      analyses, the cortical activity during 15Hz binaural beats produced networks
      characteristic of high information transfer with consistent connection strengths
      throughout the visuospatial working memory task.

PMID- 27893767
TI  - T Cells of Infants Are Mature, but Hyporeactive Due to Limited Ca2+ Influx.
AB  - CD4 T cells in human infants and adults differ in the initiation and strength of
      their responses. The molecular basis for these differences is not yet understood.
      To address this the principle key molecular events of TCR- and CD28-induced
      signaling in naive CD4 T cells, such as Ca2+ influx, NFAT expression,
      phosphorylation and translocation into the nucleus, ERK activation and IL-2
      response, were analyzed over at least the first 3 years of life. We report
      dramatically reduced IL-2 and TNFalpha responses in naive CD31+ T cells during
      infancy. Looking at the obligatory Ca2+ influx required to induce T cell
      activation and proliferation, we demonstrate characteristic patterns of
      impairment for each stage of infancy that are partly due to the differential
      usage of Ca2+ stores. Consistent with those findings, translocation of NFATc2 is
      limited, but still dependent on Ca2+ influx as demonstrated by sensitivity to
      cyclosporin A (CsA) treatment. Thus weak Ca2+ influx functions as a catalyst for
      the implementation of restricted IL-2 response in T cells during infancy. Our
      studies also define limited mobilization of Ca2+ ions as a characteristic
      property of T cells during infancy. This work adds to our understanding of
      infants' poor T cell responsiveness against pathogens.

PMID- 27893769
TI  - Assessing Visual Fields in Patients with Retinitis Pigmentosa Using a Novel
      Microperimeter with Eye Tracking: The MP-3.
AB  - PURPOSE: The purpose of the current study is to investigate the test-retest
      reproducibility of visual fields (VFs) measured with the MP-3 microperimeter, in
      patients with retinitis pigmentosa (RP). METHOD: VFs were twice measured with the
      MP-3 and also the Humphrey Field Analyzer, using the 10-2 test grid pattern in
      both perimeters, in 30 eyes (15 right and 15 left eyes) of 18 RP patients (11
      males and 7 females). Test-retest reproducibility was assessed using the mean
      absolute deviation (MAD) measure at all 68 points in the test grid.
      Reproducibility was also evaluated using the intraclass correlation coefficient
      (ICC) of VF sensitivities. RESULT: The mean sensitivity measured in the HFA 10-2
      was significantly higher than that measured in the MP-3 in both the first and
      second VF tests (p <0.0001, linear mixed model). The MAD was 2.4+/-0.6 [1.1 to
      3.6] dB for MP-3 and 2.4+/-0.9 [1.1 to 5.1] dB for HFA 10-2, which was not
      significantly different (p = 0.76, linear mixed model). The ICC value associated
      with the MP-3 VFs was 0.81+/-0.13 [0.49 to 0.98], which was significantly larger
      than that observed for the HFA 10-2 VFs: 0.77+/-0.19 [0.20 to 0.94] (p = 0.043,
      linear mixed model). CONCLUSION: The MP-3 microperimeter appears to be useful to
      evaluate central visual function in RP eyes, exhibiting test-retest
      reproducibility that is equal to, or better than, that observed in HFA 10-2 VFs.

PMID- 27893768
TI  - Macromolecular Crowding Regulates the Gene Expression Profile by Limiting
      Diffusion.
AB  - We seek to elucidate the role of macromolecular crowding in transcription and
      translation. It is well known that stochasticity in gene expression can lead to
      differential gene expression and heterogeneity in a cell population. Recent
      experimental observations by Tan et al. have improved our understanding of the
      functional role of macromolecular crowding. It can be inferred from their
      observations that macromolecular crowding can lead to robustness in gene
      expression, resulting in a more homogeneous cell population. We introduce a
      spatial stochastic model to provide insight into this process. Our results show
      that macromolecular crowding reduces noise (as measured by the kurtosis of the
      mRNA distribution) in a cell population by limiting the diffusion of
      transcription factors (i.e. removing the unstable intermediate states), and that
      crowding by large molecules reduces noise more efficiently than crowding by small
      molecules. Finally, our simulation results provide evidence that the local
      variation in chromatin density as well as the total volume exclusion of the
      chromatin in the nucleus can induce a homogenous cell population.

PMID- 27893770
TI  - Network Analysis Shows Asymmetrical Flows within a Bird Metapopulation.
AB  - How the spatial expansion of a species changes at a human time scale is a process
      difficult to determine. We studied the dispersal pattern of the French white
      stork population, using a 21-year ringing/resighting dataset. We used the graph
      theory to investigate the strength of links between 5 populations (North-East,
      North-West, Centre, West, and South) and to determine factors important for the
      birds' movements. Two clusters of populations were identified within the
      metapopulation, with most frequent movements of individuals between North-Eastern
      and Centre populations, and between North-Western and Western populations.
      Exchanges of individuals between populations were asymmetrical, where North
      Eastern and North-Western populations provided more emigrants than they received
      immigrants. Neither the geographical distance between populations, nor the
      difference in densities influenced the number of individuals exchanging between
      populations. The graph-theory approach provides a dynamic view of individual
      movements within a metapopulation and might be useful for future population
      studies in the context of conservation.

PMID- 27893771
TI  - A Nationwide Survey on Patient's versus Physician's Evaluation of Biological
      Therapy in Rheumatoid Arthritis in Relation to Disease Activity and Route of
      Administration: The Be-Raise Study.
AB  - OBJECTIVES: Biological treatment of rheumatoid arthritis (RA) is one of the
      cornerstones of current treatment strategies for the disease. Surprisingly little
      information exists on whether the route of administration affects patients'
      treatment satisfaction. It is equally unclear whether rheumatologists are able to
      accurately perceive their patients' appreciation. Thus, the Belgian Be-raise
      survey aimed to examine whether RA patient's experience of their current
      biological treatment coincided with the treating physician's perception. METHODS:
      A nationwide cross-sectional survey was conducted by 67 Belgian rheumatologists
      providing data obtained from 550 RA patients. Patients under stable dose of
      biologics for at least 6 months, were enrolled consecutively and all completed
      questionnaires. Separate questionnaires were completed by the treating
      rheumatologist which evaluated their patient's perception of the route of
      treatment administration. This study therefore evaluates whether a treating
      physician perceives the satisfaction with the route of administration to the same
      degree as the patient. RESULTS: Completed questionnaires were obtained from 293
      and 257 patients who obtained treatment via the intravenous (IV) or subcutaneous
      (SC) route of administration, respectively. 58.4% of patients were in DAS28
      CRP(3) remission. Patient satisfaction with disease control was higher (44%
      scored >= 9) than that of the treating physician (35%), regardless of the route
      of administration (p< 0.01). No differences were seen for the patients treated
      with an IV as opposed to a SC route of administration. The physician's perception
      of patient's satisfaction with disease control was markedly lower for IV treated
      patients as opposed to SC treated patients (p< 0.001). CONCLUSIONS: Patients'
      satisfaction with biological treatment is high, but there is a considerable
      mismatch between patients' and rheumatologists' appreciation on the route of
      administration of biological therapy in RA. Physicians consistently consider IV
      biological therapy to be less satisfactory. Patient's appreciation is largely
      dependent on disease control, irrespective of the route of administration.
      Therefore, and encouraging shared decision making, we suggest that physicians and
      patients discuss the route of administration of biologicals in an open way.

PMID- 27893772
TI  - A Quantitative PCR Protocol for Detection of Oxyspirura petrowi in Northern
      Bobwhites (Colinus virginianus).
AB  - Oxyspirura petrowi is a parasitic nematode that infects wild birds. This parasite
      has a broad host range, but has recently been reported in high prevalences from
      native Galliformes species in the United States. In order to better understand
      the impact O. petrowi has on wild bird populations, we developed a quantitative
      PCR protocol to detect infections in wild northern bobwhites (Colinus
      virginianus). We used paired fecal and cloacal swab samples from wild caught and
      experimentally infected northern bobwhites and matching fecal float data from
      experimentally infected birds to validate our assay. Overall we detected more
      positive birds from fecal samples than the paired cloacal swabs and there was
      strong agreement between the qPCR results from fecal samples and from fecal
      flotation (84%; kappa = 0.69 [0.53-0.84 95% CI]). We also detected O. petrowi DNA
      in ten replicates of samples spiked with one O. petrowi egg. This qPCR assay is
      an effective assay to detect O. petrowi infections in wild birds. Our results
      suggest that fecal samples are the most appropriate sample for detecting
      infections; although, cloacal swabs can be useful for determining if O. petrowi
      is circulating in a population.

PMID- 27893773
TI  - Morphology and Species Composition of Southern Adriatic Sea Leptocephali
      Evaluated Using DNA Barcoding.
AB  - Leptocephali are the characteristic larvae of the superorder Elopomorpha that are
      difficult to identify at the species level. In this study, we used DNA barcoding
      (i.e. short genetic sequences of DNA used as unique species tags) coupled with
      classical taxonomic methods to identify leptocephali in the southern Adriatic
      Sea. This information will provide an assessment of the biodiversity of the eel
      larvae in this region. A total of 2,785 leptocephali were collected, and using
      external morphology were assigned to seven morphotypes: Ariosoma balearicum,
      Conger conger, Gnathophis mystax, Facciolella sp., Nettastoma melanurum, Dalophis
      imberbis and Chlopsis bicolor. Collectively, these seven morphotypes are
      considered to be a good proxy for the Anguilliformes community (the main order of
      the Elopomorpha) in the southern Adriatic Sea (to date, seven families and
      sixteen species have been recorded in this region). Interestingly, the higher
      number of G. mystax larvae collected suggests an increased abundance of this
      genus. To validate the morphological identifications, we sequenced 61
      leptocephali (at a 655 bp fragment from the cytochrome oxidase subunit 1
      mitochondrial region) and developed barcode vouchers for the seven morphotypes.
      Using genetic information from reference databases, we validated three of these
      morphotypes. Where reference sequences were unavailable, we generated barcodes
      for both adult and juvenile forms to provide additional genetic information.
      Using this integrated approach allowed us to characterize a new species of
      Facciolella in the Adriatic Sea for the first time. Moreover, we also revealed a
      lack of differentiation, at the species level, between G. mistax and G.
      bathytopos, a western Atlantic Ocean species. Our morphological and barcode data
      have been published in the Barcoding of the Adriatic Leptocephali database. This
      work represents the first contribution to a wider project that aims to create a
      barcode database to support the assessment of leptocephali diversity in the
      Mediterranean Sea.

PMID- 27893775
TI  - Extinction Debt and Colonizer Credit on a Habitat Perturbed Fishing Bank.
AB  - Temporal changes in occupancy of the Georges Bank (NE USA) fish and invertebrate
      community were examined and interpreted in the context of systems ecological
      theory of extinction debt (EDT). EDT posits that in a closed system with a mix of
      competitor and colonizer species and experiencing habitat fragmentation and loss,
      the competitor species will show a gradual decline in fitness (occupancy)
      eventually leading to their extinction (extirpation) over multiple generations. A
      corollary of this is a colonizer credit, where colonizer species occupancy may
      increase with fragmentation because the disturbance gives that life history a
      transient relative competitive advantage. We found that competitor species
      occupancy decreased in time concomitant with an increase in occupancy of
      colonizer species and this may be related to habitat fragmentation or loss owing
      to industrialized bottom trawl fishing. Mean species richness increased over time
      which suggests less specialization (decreased dominance) of the assemblage that
      may result from habitat homogenization. These analyses also showed that when
      abundance of species was decreased by fishing but eventually returned to previous
      levels, on average it had a lower occupancy than earlier in the series which
      could increase their vulnerability to depletion by fishing. Changing occupancy
      and diversity patterns of the community over time is consistent with EDT which
      can be exacerbated by direct impacts of fishery removals as well as climate
      change impacts on the fish community assemblage.

PMID- 27893774
TI  - Multivalent Interactions of Human Primary Amine Oxidase with the V and C22
      Domains of Sialic Acid-Binding Immunoglobulin-Like Lectin-9 Regulate Its Binding
      and Amine Oxidase Activity.
AB  - Sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) on leukocyte surface
      is a counter-receptor for endothelial cell surface adhesin, human primary amine
      oxidase (hAOC3), a target protein for anti-inflammatory agents. This interaction
      can be used to detect inflammation and cancer in vivo, since the labeled peptides
      derived from the second C2 domain (C22) of Siglec-9 specifically bind to the
      inflammation-inducible hAOC3. As limited knowledge on the interaction between
      Siglec-9 and hAOC3 has hampered both hAOC3-targeted drug design and in vivo
      imaging applications, we have now produced and purified the extracellular region
      of Siglec-9 (Siglec-9-EC) consisting of the V, C21 and C22 domains, modeled its
      3D structure and characterized the hAOC3-Siglec-9 interactions using biophysical
      methods and activity/inhibition assays. Our results assign individual, previously
      unknown roles for the V and C22 domains. The V domain is responsible for the
      unusually tight Siglec-9-hAOC3 interactions whereas the intact C22 domain of
      Siglec-9 is required for modulating the enzymatic activity of hAOC3, crucial for
      the hAOC3-mediated leukocyte trafficking. By characterizing the Siglec-9-EC
      mutants, we could conclude that R120 in the V domain likely interacts with the
      terminal sialic acids of hAOC3 attached glycans whereas residues R284 and R290 in
      C22 are involved in the interactions with the active site channel of hAOC3.
      Furthermore, the C22 domain binding enhances the enzymatic activity of hAOC3
      although the sialic acid-binding capacity of the V domain of Siglec-9 is
      abolished by the R120S mutation. To conclude, our results prove that the V and
      C22 domains of Siglec-9-EC interact with hAOC3 in a multifaceted and unique way,
      forming both glycan-mediated and direct protein-protein interactions,
      respectively. The reported results on the mechanism of the Siglec-9-hAOC3
      interaction are valuable for the development of hAOC3-targeted therapeutics and
      diagnostic tools.

PMID- 27893776
TI  - Diagnostic Value and Interreader Agreement of the Pancreaticolienal Gap in
      Pancreatic Cancer on MDCT.
AB  - OBJECTIVE: The aim of this retrospective study was to evaluate the diagnostic
      value and measure interreader agreement of the pancreaticolienal gap (PLG) in the
      assessment of imaging features of pancreatic carcinoma (PC) on contrast-enhanced
      multi-detector computed tomography (CE-MDCT). MATERIALS AND METHODS: CE-MDCT
      studies in the portal venous phase were retrospectively reviewed for 66 patients
      with PC. The age- and gender-matched control group comprised 103 healthy
      individuals. Three radiologists with different levels of experience independently
      measured the PLG (the minimum distance of the pancreatic tail to the nearest
      border of the spleen) in the axial plane. The interreader agreement of the PLG
      and the receiver operating characteristic (ROC) curve was used to calculate the
      accuracy of the technique. RESULTS: While the control group (n = 103) showed a
      median PLG of 3 mm (Range: 0 - 39mm) the PC patients had a significantly larger
      PLG of 15mm (Range: 0 - 53mm)(p < 0.0001). A ROC curve demonstrated a cutoff
      value of >12 mm for PC, with a sensitivity of 58.2% (95% CI = 45.5-70.1),
      specificity of 84.0% (95% CI = 75.6-90.4) and an area under the ROC curve of
      0.714 (95% CI = 0.641 to 0.780). The mean interreader agreement showed
      correlation coefficient r of 0.9159. The extent of the PLG did not correlate with
      tumor stage but did correlate with pancreatic density (fatty involution) and age,
      the density decreased by 4.1 HU and the PLG increased by 0.8 mm within every 10
      y. CONCLUSION: The significant interreader agreement supports the use of the PLG
      as a characterizing feature of pancreatic cancer independent of the tumor stage
      on an axial plane. The increase in the PLG with age may represent physiological
      atrophy of the pancreatic tail.

PMID- 27893777
TI  - Simulating Next-Generation Sequencing Datasets from Empirical Mutation and
      Sequencing Models.
AB  - An obstacle to validating and benchmarking methods for genome analysis is that
      there are few reference datasets available for which the "ground truth" about the
      mutational landscape of the sample genome is known and fully validated.
      Additionally, the free and public availability of real human genome datasets is
      incompatible with the preservation of donor privacy. In order to better analyze
      and understand genomic data, we need test datasets that model all variants,
      reflecting known biology as well as sequencing artifacts. Read simulators can
      fulfill this requirement, but are often criticized for limited resemblance to
      true data and overall inflexibility. We present NEAT (NExt-generation sequencing
      Analysis Toolkit), a set of tools that not only includes an easy-to-use read
      simulator, but also scripts to facilitate variant comparison and tool evaluation.
      NEAT has a wide variety of tunable parameters which can be set manually on the
      default model or parameterized using real datasets. The software is freely
      available at github.com/zstephens/neat-genreads.

PMID- 27893778
TI  - Mycobacterium ulcerans Mouse Model Refinement for Pre-Clinical Profiling of
      Vaccine Candidates.
AB  - Buruli Ulcer is a neglected tropical disease leading to extensive disabilities
      and morbidity in West Africa. In this paper we sought to characterize various
      strains of Mycobacterium ulcerans (M.ulcerans) with different origins and
      laboratory passage records while refining a mouse model for Buruli ulcer. We
      described, compared and followed the kinetics of the histo-pathological outcome
      of infection of a collection of strains at various anatomical sites of infection
      in order to find a suitable model for further immunization studies. Moreover we
      compared the outcome of infection in C57Bl/6 and Balbc/J mice. Specifically we
      described thoroughly one M. ulcerans strain characterized by slow growth rate and
      limited tissue necrosis, which presents close ressemblance with the infection
      kinetics in humans. This strain caused macrophages as well as T and B cells
      infiltration, correlating with mycobacterial proliferation at the site of
      infection as well as in the draining lymph nodes, making it a suitable strain to
      screen vaccine candidates efficacy.

PMID- 27893780
TI  - Identifying Key Drivers of Return Reversal with Dynamical Bayesian Factor Graph.
AB  - In the stock market, return reversal occurs when investors sell overbought stocks
      and buy oversold stocks, reversing the stocks' price trends. In this paper, we
      develop a new method to identify key drivers of return reversal by incorporating
      a comprehensive set of factors derived from different economic theories into one
      unified dynamical Bayesian factor graph. We then use the model to depict factor
      relationships and their dynamics, from which we make some interesting discoveries
      about the mechanism behind return reversals. Through extensive experiments on the
      US stock market, we conclude that among the various factors, the liquidity
      factors consistently emerge as key drivers of return reversal, which is in
      support of the theory of liquidity effect. Specifically, we find that stocks with
      high turnover rates or high Amihud illiquidity measures have a greater
      probability of experiencing return reversals. Apart from the consistent drivers,
      we find other drivers of return reversal that generally change from year to year,
      and they serve as important characteristics for evaluating the trends of stock
      returns. Besides, we also identify some seldom discussed yet enlightening inter
      factor relationships, one of which shows that stocks in Finance and Insurance
      industry are more likely to have high Amihud illiquidity measures in comparison
      with those in other industries. These conclusions are robust for return reversals
      under different thresholds.

PMID- 27893779
TI  - Rapid Recovery of Visual Function Associated with Blue Cone Ablation in
      Zebrafish.
AB  - Hurdles in the treatment of retinal degeneration include managing the functional
      rewiring of surviving photoreceptors and integration of any newly added cells
      into the remaining second-order retinal neurons. Zebrafish are the premier
      genetic model for such questions, and we present two new transgenic lines
      allowing us to contrast vision loss and recovery following conditional ablation
      of specific cone types: UV or blue cones. The ablation of each cone type proved
      to be thorough (killing 80% of cells in each intended cone class), specific, and
      cell-autonomous. We assessed the loss and recovery of vision in larvae via the
      optomotor behavioural response (OMR). This visually mediated behaviour decreased
      to about 5% or 20% of control levels following ablation of UV or blue cones,
      respectively (P<0.05). We further assessed ocular photoreception by measuring the
      effects of UV light on body pigmentation, and observed that photoreceptor
      deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR
      results. This corroborated and extended previous conclusions that UV cones are
      required photoreceptors for modulating body pigmentation, addressing assumptions
      that were unavoidable in previous experiments. Functional vision recovery
      following UV cone ablation was robust, as measured by both assays, returning to
      control levels within four days. In contrast, robust functional recovery
      following blue cone ablation was unexpectedly rapid, returning to normal levels
      within 24 hours after ablation. Ablation of cones led to increased proliferation
      in the retina, though the rapid recovery of vision following blue cone ablation
      was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual
      recovery occurs following ablation of some, but not all, cone subtypes,
      suggesting an opportunity to contrast and dissect the sources and mechanisms of
      outer retinal recovery during cone photoreceptor death and regeneration.

PMID- 27893781
TI  - Salicylic Acid Is Involved in the Basal Resistance of Tomato Plants to Citrus
      Exocortis Viroid and Tomato Spotted Wilt Virus.
AB  - Tomato plants expressing the NahG transgene, which prevents accumulation of
      endogenous salicylic acid (SA), were used to study the importance of the SA
      signalling pathway in basal defence against Citrus Exocortis Viroid (CEVd) or
      Tomato Spotted Wilt Virus (TSWV). The lack of SA accumulation in the CEVd- or
      TSWV-infected NahG tomato plants led to an early and dramatic disease phenotype,
      as compared to that observed in the corresponding parental Money Maker. Addition
      of acibenzolar-S-methyl, a benzothiadiazole (BTH), which activates the systemic
      acquired resistance pathway downstream of SA signalling, improves resistance of
      NahG tomato plants to CEVd and TSWV. CEVd and TSWV inoculation induced the
      accumulation of the hydroxycinnamic amides p-coumaroyltyramine, feruloyltyramine,
      caffeoylputrescine, and feruloylputrescine, and the defence related proteins PR1
      and P23 in NahG plants earlier and with more intensity than in Money Maker
      plants, indicating that SA is not essential for the induction of these plant
      defence metabolites and proteins. In addition, NahG plants produced very high
      levels of ethylene upon CEVd or TSWV infection when compared with infected Money
      Maker plants, indicating that the absence of SA produced additional effects on
      other metabolic pathways. This is the first report to show that SA is an
      important component of basal resistance of tomato plants to both CEVd and TSWV,
      indicating that SA-dependent defence mechanisms play a key role in limiting the
      severity of symptoms in CEVd- and TSWV-infected NahG tomato plants.

PMID- 27893782
TI  - Beneficial Effects of Metformin and/or Salicylate on Palmitate- or TNFalpha
      Induced Neuroinflammatory Marker and Neuropeptide Gene Regulation in Immortalized
      NPY/AgRP Neurons.
AB  - Neuropeptide Y (NPY)/Agouti-related peptide (AgRP)-expressing neurons in the
      hypothalamus induce feeding and decrease energy expenditure. With consumption of
      a diet high in fat, there is an increase in circulating saturated free fatty
      acids, including palmitate, leading to the development of neuroinflammation and
      secretion of cytokines, such as TNFalpha, and in turn activation of the canonical
      IKKbeta/NFkappaB cascade. We describe a model of palmitate- and TNFalpha-induced
      neuroinflammation in a functionally characterized, immortalized NPY/AgRP
      expressing cell model, mHypoE-46, to study whether the anti-diabetic metformin
      alone or in combination with the anti-inflammatory agent salicylate can
      ameliorate these detrimental effects. Treatment with palmitate increased mRNA
      expression of feeding peptides Npy and Agrp, and inflammatory cytokines Tnfa and
      Il-6, whereas treatment with TNFalpha increased mRNA expression of Npy, Nfkb,
      Ikba, Tnfa, and Il-6. The effects of metformin and/or sodium salicylate on these
      genes were assessed. Metformin increased phosphorylation of AMPK and S6K, while
      sodium salicylate increased phospho-AMPK and decreased phospho-S6K, but neither
      had any effect on phospho-ERK, -JNK or -p38 in the mHypoE-46 NPY/AgRP neurons.
      Furthermore, we utilized a pre-treatment and/or co-treatment paradigm to model
      potential clinical regimens. We determined co-treatment with metformin or sodium
      salicylate alone was successful in alleviating changes observed in feeding
      peptide mRNA regulation, whereas a preventative pre-treatment with metformin and
      sodium salicylate together was able to alleviate palmitate- and TNFalpha-induced
      induction of NPY and/or AgRP mRNA levels. These results highlight important
      differences in reactive versus preventative treatments on palmitate- and TNFalpha
      induced neuroinflammation in NPY/AgRP neurons.

PMID- 27893783
TI  - Role of PTEN in Oxidative Stress and DNA Damage in the Liver of Whole-Body Pten
      Haplodeficient Mice.
AB  - Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic
      fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular
      mechanisms of carcinogenesis in this context are only partially understood. High
      blood insulin levels are typical in early T2DM and excessive insulin can cause
      elevated reactive oxygen species (ROS) production and genomic instability. ROS
      are important for various cellular functions in signaling and host defense.
      However, elevated ROS formation is thought to be involved in cancer induction. In
      the molecular events from insulin receptor binding to genomic damage, some
      signaling steps have been identified, pointing at the PI3K/AKT pathway. For
      further elucidation Phosphatase and Tensin homolog (Pten), a tumour suppressor
      phosphatase that plays a role in insulin signaling by negative regulation of
      PI3K/AKT and its downstream targets, was investigated here. Dihydroethidium (DHE)
      staining was used to detect ROS formation in immortalized human hepatocytes.
      Comet assay and micronucleus test were performed to investigate genomic damage in
      vitro. In liver samples, DHE staining and western blot detection of HSP70 and HO
      1 were performed to evaluate oxidative stress response. DNA double strand breaks
      (DSBs) were detected by immunohistostaining. Inhibition of PTEN with the
      pharmacologic inhibitor VO-OHpic resulted in increased ROS production and genomic
      damage in a liver cell line. Knockdown of Pten in a mouse model yielded increased
      oxidative stress levels, detected by ROS levels and expression of the two stress
      proteins HSP70 and HO-1 and elevated genomic damage in the liver, which was
      significant in mice fed with a high fat diet. We conclude that PTEN is involved
      in oxidative stress and genomic damage induction in vitro and that this may also
      explain the in vivo observations. This further supports the hypothesis that the
      PI3K/AKT pathway is responsible for damaging effects of high levels of insulin.

PMID- 27893784
TI  - Circadian Variation of Plasminogen-Activator-Inhibitor-1 Levels in Children with
      Meningococcal Sepsis.
AB  - OBJECTIVE: To study whether the circadian variation of plasminogen-activator
      inhibitor-1 (PAI-1) levels, with high morning levels, is associated with poor
      outcome of children with meningococcal sepsis presenting in the morning hours.
      DESIGN: Retrospective analysis of prospectively collected clinical and laboratory
      data. SETTING: Single center study at Erasmus MC-Sophia Children's Hospital,
      Rotterdam, the Netherlands. SUBJECTS: 184 patients aged 3 weeks to 18 years with
      meningococcal sepsis. In 36 of these children, PAI-1 levels at admission to the
      PICU were measured in plasma by ELISA. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Circadian variation was studied by dividing one day in blocks of 6
      hours. Patients admitted between 6:00 am and 12:00 am had increased illness
      severity scores and higher PAI-1 levels (n = 9, median 6912 ng/mL, IQR 5808
      15600) compared to patients admitted at night (P = 0.019, n = 9, median 3546
      ng/mL, IQR 1668-6118) or in the afternoon (P = 0.007, n = 7, median 4224 ng/mL,
      IQR 1804-5790). In 184 patients, analysis of circadian variation in relation to
      outcome showed more deaths, amputations and need for skin grafts in patients
      admitted to the PICU between 6:00 am and 12:00 am than patients admitted during
      the rest of the day (P = 0.009). CONCLUSIONS: Circadian variation of PAI-1 levels
      is present in children with meningococcal sepsis and is associated with illness
      severity, with a peak level in the morning. Whether circadian variation is an
      independent risk factor for morbidity and mortality in meningococcal sepsis needs
      to be explored in future studies.

PMID- 27893785
TI  - Are Older Adults Physically Active Enough - A Matter of Assessment Method? The
      Generation 100 Study.
AB  - INTRODUCTION: Physical activity (PA) is beneficial for general health. As a
      result, adults around the world are recommended to undertake regular PA of either
      absolute or relative intensity. Traditionally, adherence to PA recommendation is
      assessed by accelerometers that record absolute intensity thresholds. Since
      ageing often results in a decrease in cardiorespiratory fitness (CRF), older
      adults (aged > 65 years) might be more susceptible to not meeting the PA
      recommendation when measured in absolute terms. The aim of the present study was
      to compare the adherence to the PA recommendation using both absolute and
      relative thresholds. Additionally, we aimed to report the reference values for
      overall PA in a large sample of Norwegian older adults. METHODS: PA was assessed
      for 7 days using the Actigraph GT3X+ accelerometer in 1219 older adults (624
      females) aged 70-77 years. Overall PA was measured as counts per minute (CPM) and
      steps. Absolute and relative moderate-to-vigorous PA (MVPA) thresholds were
      applied to quantify adherence to PA recommendation. The relative MVPA thresholds
      were developed specifically for the Generation 100 population sample. CRF was
      directly measured as peak oxygen uptake (VO2peak). RESULTS: Proportions meeting
      PA recommendation were 29% and 71% when utilizing absolute and relative MVPA,
      respectively. More females met the relative PA recommendation compared to males.
      Overall PA was higher among the youngest age group. Older adults with medium- and
      high levels of CRF were more physically active, compared to those with the lowest
      levels of CRF. CONCLUSION: This is the first study to compare adherence to PA
      recommendation, using absolute and relative intensity thresholds among older
      adults. The present study clearly illustrates the consequences of using different
      methodological approaches to surveillance of PA across age, gender and CRF in a
      population of older adults.

PMID- 27893786
TI  - Extending Integrate-and-Fire Model Neurons to Account for the Effects of Weak
      Electric Fields and Input Filtering Mediated by the Dendrite.
AB  - Transcranial brain stimulation and evidence of ephaptic coupling have recently
      sparked strong interests in understanding the effects of weak electric fields on
      the dynamics of brain networks and of coupled populations of neurons. The
      collective dynamics of large neuronal populations can be efficiently studied
      using single-compartment (point) model neurons of the integrate-and-fire (IF)
      type as their elements. These models, however, lack the dendritic morphology
      required to biophysically describe the effect of an extracellular electric field
      on the neuronal membrane voltage. Here, we extend the IF point neuron models to
      accurately reflect morphology dependent electric field effects extracted from a
      canonical spatial "ball-and-stick" (BS) neuron model. Even in the absence of an
      extracellular field, neuronal morphology by itself strongly affects the cellular
      response properties. We, therefore, derive additional components for leaky and
      nonlinear IF neuron models to reproduce the subthreshold voltage and spiking
      dynamics of the BS model exposed to both fluctuating somatic and dendritic inputs
      and an extracellular electric field. We show that an oscillatory electric field
      causes spike rate resonance, or equivalently, pronounced spike to field
      coherence. Its resonance frequency depends on the location of the synaptic
      background inputs. For somatic inputs the resonance appears in the beta and gamma
      frequency range, whereas for distal dendritic inputs it is shifted to even higher
      frequencies. Irrespective of an external electric field, the presence of a
      dendritic cable attenuates the subthreshold response at the soma to slowly
      varying somatic inputs while implementing a low-pass filter for distal dendritic
      inputs. Our point neuron model extension is straightforward to implement and is
      computationally much more efficient compared to the original BS model. It is well
      suited for studying the dynamics of large populations of neurons with
      heterogeneous dendritic morphology with (and without) the influence of weak
      external electric fields.

PMID- 27893787
TI  - Selection Signatures in Four Lignin Genes from Switchgrass Populations
      Divergently Selected for In Vitro Dry Matter Digestibility.
AB  - Switchgrass is undergoing development as a dedicated cellulosic bioenergy crop.
      Fermentation of lignocellulosic biomass to ethanol in a bioenergy system or to
      volatile fatty acids in a livestock production system is strongly and negatively
      influenced by lignification of cell walls. This study detects specific loci that
      exhibit selection signatures across switchgrass breeding populations that differ
      in in vitro dry matter digestibility (IVDMD), ethanol yield, and lignin
      concentration. Allele frequency changes in candidate genes were used to detect
      loci under selection. Out of the 183 polymorphisms identified in the four
      candidate genes, twenty-five loci in the intron regions and four loci in coding
      regions were found to display a selection signature. All loci in the coding
      regions are synonymous substitutions. Selection in both directions were observed
      on polymorphisms that appeared to be under selection. Genetic diversity and
      linkage disequilibrium within the candidate genes were low. The recurrent
      divergent selection caused excessive moderate allele frequencies in the cycle 3
      reduced lignin population as compared to the base population. This study provides
      valuable insight on genetic changes occurring in short-term selection in the
      polyploid populations, and discovered potential markers for breeding switchgrass
      with improved biomass quality.

PMID- 27893789
TI  - Characterization of the Canine MHC Class I DLA-88*50101 Peptide Binding Motif as
      a Prerequisite for Canine T Cell Immunotherapy.
AB  - There are limitations in pre-clinical settings using mice as a basis for clinical
      development in humans. In cancer, similarities exist between humans and dogs;
      thus, the dog patient can be a link in the transition from laboratory research on
      mouse models to clinical trials in humans. Knowledge of the peptides presented on
      MHC molecules is fundamental for the development of highly specific T cell-based
      immunotherapies. This information is available for human MHC molecules but is
      absent for the canine MHC. In the present study, we characterized the binding
      motif of dog leukocyte antigen (DLA) class I allele DLA-88*50101, using human C1R
      and K562 transfected cells expressing the DLA-88*50101 heavy chain. MHC class I
      immunoaffinity-purification revealed 3720 DLA-88*50101 derived peptides, which
      enabled the determination of major anchor positions. The characterized binding
      motif of DLA-88*50101 was similar to HLA-A*02:01. Peptide binding analyses on HLA
      A*02:01 and DLA-88*50101 via flow cytometry showed weak binding of DLA-88*50101
      derived peptides to HLA-A*02:01, and vice versa. Our results present for the
      first time a detailed peptide binding motif of the canine MHC class I allelic
      product DLA-88*50101. These data support the goal of establishing dogs as a
      suitable animal model for the evaluation and development of T cell-based cancer
      immunotherapies, benefiting both dog and human patients.

PMID- 27893788
TI  - Effects of High-Fat Diet on Stress Response in Male and Female Wildtype and
      Prolactin Knockout Mice.
AB  - Prolactin (PRL) is well characterized for its roles in initiation and maintenance
      of lactation, and it also suppresses stress-induced responses. Feeding a high-fat
      diet (HFD) disrupts activity of the hypothalamic-pituitary-adrenal (HPA) axis.
      Whether PRL regulates HPA axis activation under HFD feeding is not clear. Male
      and female wildtype (WT) and PRL knockout (KO) mice were fed either a standard
      low-fat diet (LFD) or HFD for 12 weeks. Circulating corticosterone (CORT) levels
      were measured before, during, and after mice were subjected to an acute restraint
      stress or remained in their home cages as no stress controls. HFD feeding
      increased leptin levels, but the increase was lower in KO than in WT mice. All
      stressed female groups and only LFD-fed stressed males had elevated CORT levels
      compared to their no stress same-sex counterparts regardless of genotype. These
      results indicated that HFD consumption blunted the HPA axis response to acute
      stress in males but not females. Additionally, basal hypothalamic CRH content was
      lower in HFD than LFD males, but was similar among female groups. Furthermore,
      although basal CORT levels were similar among KO and WT groups, CORT levels were
      higher in KO mice than their WT counterparts during stress, suggesting that loss
      of PRL led to greater HPA axis activation. Basal PRL receptor mRNA levels in the
      choroid plexus were higher in HFD than LFD same-sex counterparts, suggesting
      activation of central PRL's action by HFD feeding in both males and females.
      Current results confirmed PRL's roles in suppression of the stress-induced HPA
      axis activation. Although HFD feeding activated central PRL's action in both
      sexes, only the male HPA axis was dampened by HFD feeding.

PMID- 27893790
TI  - Detection of a cfr(B) Variant in German Enterococcus faecium Clinical Isolates
      and the Impact on Linezolid Resistance in Enterococcus spp.
AB  - The National Reference Centre for Staphylococci and Enterococci in Germany has
      received an increasing number of clinical linezolid-resistant E. faecium isolates
      in recent years. Five isolates harbored a cfr(B) variant gene locus the product
      of which is capable of conferring linezolid resistance. The cfr(B)-like
      methyltransferase gene was also detected in Clostridium difficile. Antimicrobial
      susceptibility was determined for cfr(B)-positive and linezolid-resistant E.
      faecium isolates and two isogenic C. difficile strains. All strains were
      subjected to whole genome sequencing and analyzed with respect to mutations in
      the 23S rDNA, rplC, rplD and rplV genes and integration sites of the cfr(B)
      variant locus. To evaluate methyltransferase function, the cfr(B) variant of
      Enterococcus and Clostridium was expressed in both E. coli and Enterococcus spp.
      Ribosomal target site mutations were detected in E. faecium strains but absent in
      clostridia. Sequencing revealed 99.9% identity between cfr(B) of Enterococcus and
      cfr of Clostridium. The methyltransferase gene is encoded by transposon Tn6218
      which was present in C. difficile Ox3196, truncated in some E. faecium and absent
      in C. difficile Ox3206. The latter finding explains the lack of linezolid and
      chloramphenicol resistance in C. difficile Ox3206 and demonstrates for the first
      time a direct correlation of elevated linezolid MICs in C. difficile upon cfr
      acquisition. Tn6218 insertion sites revealed novel target loci for integration,
      both within the bacterial chromosome and as an integral part of plasmids.
      Importantly, the very first plasmid-association of a cfr(B) variant was observed.
      Although we failed to measure cfr(B)-mediated resistance in transformed
      laboratory strains the occurrence of the multidrug resistance gene cfr on
      putatively highly mobile and/or extrachromosomal DNA in clinical isolates is
      worrisome with respect to dissemination of antibiotic resistances.

PMID- 27893791
TI  - Toward a Nonspeech Test of Auditory Cognition: Semantic Context Effects in
      Environmental Sound Identification in Adults of Varying Age and Hearing
      Abilities.
AB  - OBJECTIVE: Sounds in everyday environments tend to follow one another as events
      unfold over time. The tacit knowledge of contextual relationships among
      environmental sounds can influence their perception. We examined the effect of
      semantic context on the identification of sequences of environmental sounds by
      adults of varying age and hearing abilities, with an aim to develop a nonspeech
      test of auditory cognition. METHOD: The familiar environmental sound test (FEST)
      consisted of 25 individual sounds arranged into ten five-sound sequences: five
      contextually coherent and five incoherent. After hearing each sequence, listeners
      identified each sound and arranged them in the presentation order. FEST was
      administered to young normal-hearing, middle-to-older normal-hearing, and middle
      to-older hearing-impaired adults (Experiment 1), and to postlingual cochlear
      implant users and young normal-hearing adults tested through vocoder-simulated
      implants (Experiment 2). RESULTS: FEST scores revealed a strong positive effect
      of semantic context in all listener groups, with young normal-hearing listeners
      outperforming other groups. FEST scores also correlated with other measures of
      cognitive ability, and for CI users, with the intelligibility of speech-in-noise.
      CONCLUSIONS: Being sensitive to semantic context effects, FEST can serve as a
      nonspeech test of auditory cognition for diverse listener populations to assess
      and potentially improve everyday listening skills.

PMID- 27893792
TI  - Renal Cell Carcinoma Associated with Xp11.2 Translocation/TFE3 Gene Fusions:
      Clinical Features, Treatments and Prognosis.
AB  - To investigate the clinical characteristics, treatments and prognosis of renal
      cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions (Xp11.2
      tRCC), the epidemiological features and treatment results of 34 cases of Xp11.2
      tRCC, which were diagnosed by immunohistochemistry staining of TFE3 and
      fluorescence in situ hybridization at our center, were retrospectively reviewed.
      The 34 patients included 21 females and 13 males aged 3 to 64 years (median age:
      27 years). Four patients were children or adolescents (<18 years of age), and 26
      patients were young or middle-aged adults (18-45 years). Radical nephrectomy was
      performed on 25 patients. Laparoscopic nephron-sparing surgery was performed on 9
      patients who presented with an isolated mass with a small diameter (<7 cm) and
      well-defined boundary on computed tomography imaging. Postoperative staging
      showed that 25 cases (73.53%) were at stage I/II, while 9 cases (26.47%) were at
      stage III/IV. All stage I/II patients received a favorable prognosis with a three
      year overall survival rate of 100%, including the patients who underwent
      laparoscopic nephron-sparing surgery. With the exception of 2 children, the other
      7 stage III/IV patients died or developed recurrence with a median follow-up of
      29 months. On univariate analysis, maximum diameter, adjuvant treatment, TNM
      stage, lymph node metastasis, inferior vena cava tumor thrombosis and tumor
      boundary were identified as statistically significant factors impacting survival
      (P<0.05). Multivariate analysis indicated that TNM stage and inferior vena cava
      tumor thrombosis were independent prognostic factors (P<0.05). In conclusion,
      Xp11.2 tRCC is a rare subtype of renal cell carcinoma that mainly occurs in young
      females. Nephron-sparing surgery was confirmed effective preliminarily in the
      treatment of small Xp11.2 tRCCs with clear rims. Advanced TNM stage and inferior
      vena cava tumor thrombosis were associated with poor prognosis.

PMID- 27893794
TI  - Single Amino Acid Repeats in the Proteome World: Structural, Functional, and
      Evolutionary Insights.
AB  - Microsatellites or simple sequence repeats (SSR) are abundant, highly diverse
      stretches of short DNA repeats present in all genomes. Tandem
      mono/tri/hexanucleotide repeats in the coding regions contribute to single amino
      acids repeats (SAARs) in the proteome. While SSRs in the coding region always
      result in amino acid repeats, a majority of SAARs arise due to a combination of
      various codons representing the same amino acid and not as a consequence of SSR
      events. Certain amino acids are abundant in repeat regions indicating a positive
      selection pressure behind the accumulation of SAARs. By analysing 22 proteomes
      including the human proteome, we explored the functional and structural
      relationship of amino acid repeats in an evolutionary context. Only ~15% of
      repeats are present in any known functional domain, while ~74% of repeats are
      present in the disordered regions, suggesting that SAARs add to the functionality
      of proteins by providing flexibility, stability and act as linker elements
      between domains. Comparison of SAAR containing proteins across species reveals
      that while shorter repeats are conserved among orthologs, proteins with longer
      repeats, >15 amino acids, are unique to the respective organism. Lysine repeats
      are well conserved among orthologs with respect to their length and number of
      occurrences in a protein. Other amino acids such as glutamic acid, proline,
      serine and alanine repeats are generally conserved among the orthologs with
      varying repeat lengths. These findings suggest that SAARs have accumulated in the
      proteome under positive selection pressure and that they provide flexibility for
      optimal folding of functional/structural domains of proteins. The insights gained
      from our observations can help in effective designing and engineering of proteins
      with novel features.

PMID- 27893793
TI  - Field Trial of an Aerially-Distributed Tuberculosis Vaccine in a Low-Density
      Wildlife Population of Brushtail Possums (Trichosurus vulpecula).
AB  - Oral-delivery Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine in a
      lipid matrix has been shown to confer protection against M. bovis infection and
      reduce the severity of tuberculosis (TB) when fed to brushtail possums
      (Trichosurus vulpecula), the major wildlife vector of bovine TB in New Zealand.
      Here we demonstrate the feasibility of aerial delivery of this live vaccine in
      bait form to an M. bovis-infected wild possum population, and subsequently assess
      vaccine uptake and field efficacy. Pre-trial studies indicated a resident possum
      population at very low density (<0.6 possums/ha) at the field site, with a 5.1%
      prevalence of macroscopic TB lesions. Pilot studies indicated that flavoured
      lipid matrix baits in weather-proof sachets could be successfully sown aerially
      via helicopter and were palatable to, and likely to be consumed by, a majority of
      wild possums under free-choice conditions. Subsequently, sachet-held lipid baits
      containing live BCG vaccine were sown at 3 baits/ha over a 1360 ha area, equating
      to >5 baits available per possum. Blood sampling conducted two months later
      provided some evidence of vaccine uptake. A necropsy survey conducted one year
      later identified a lower prevalence of culture-confirmed M. bovis infection
      and/or gross TB lesions among adult possums in vaccinated areas (1.1% prevalence;
      95% CI, 0-3.3%, n = 92) than in unvaccinated areas (5.6%; 0.7-10.5%, n = 89); P =
      0.098. Although not statistically different, the 81% efficacy in protecting
      possums against natural infection calculated from these data is within the range
      of previous estimates of vaccine efficacy in trials where BCG vaccine was
      delivered manually. We conclude that, with further straightforward refinement to
      improve free-choice uptake, aerial delivery of oral BCG vaccine is likely to be
      effective in controlling TB in wild possums. We briefly discuss contexts in which
      this could potentially become an important complementary tool in achieving
      national eradication of TB from New Zealand wildlife.

PMID- 27893796
TI  - Attitudes to Mental Illness and Its Demographic Correlates among General
      Population in Singapore.
AB  - BACKGROUND: Public attitudes to mental illness could influence how the public
      interact with, provide opportunities for, and help people with mental illness.
      AIMS: This study aims to explore the underlying factors of the Attitudes to
      Mental Illness questionnaire among the general population in Singapore and the
      socio-demographic correlates of each factor. METHODS: From March 2014 to April
      2015, a nation-wide cross-sectional survey on mental health literacy with 3,006
      participants was conducted in Singapore. RESULTS: Factor analysis revealed a 4
      factor structure for the Attitudes to Mental Illness questionnaire among the
      Singapore general population, namely social distancing, tolerance/support for
      community care, social restrictiveness, and prejudice and misconception. Older
      age, male gender, lower education and socio-economic status were associated with
      more negative attitudes towards the mentally ill. Chinese showed more negative
      attitudes than Indians and Malays (except for prejudice and misconception).
      CONCLUSIONS: There is a need for culture-specific interventions, and the
      associated factors identified in this study should be considered for future
      attitude campaigns.

PMID- 27893795
TI  - Virulence of Mycobacterium tuberculosis after Acquisition of Isoniazid
      Resistance: Individual Nature of katG Mutants and the Possible Role of AhpC.
AB  - In the last decade, there were 10 million new tuberculosis cases per year
      globally. Around 9.5% of these cases were caused by isoniazid resistant (INHr)
      Mycobacterium tuberculosis (Mtb) strains. Although isoniazid resistance in Mtb is
      multigenic, mutations in the catalase-peroxidase (katG) gene predominate among
      the INHr strains. The effect of these drug-resistance-conferring mutations on Mtb
      fitness and virulence is variable. Here, we assessed differences in bacterial
      growth, immune response and pathology induced by Mtb strains harboring mutations
      at the N-terminus of the katG gene. We studied one laboratory and one clinically
      isolated Mtb clonal pair from different genetic lineages. The INHr strain in each
      pair had one and two katG mutations with significantly reduced levels of the
      enzyme and peroxidase activity. Both strains share the V1A mutation, while the
      double mutant clinical INHr had also the novel E3V katG mutation. Four groups of
      C57BL/6 mice were infected with one of the Mtb strains previously described. We
      observed a strong reduction in virulence (reduced bacterial growth), lower
      induction of proinflammatory cytokines and significantly reduced pathology scores
      in mice infected with the clinical INHr strain compared to the infection caused
      by its INHs progenitor strain. On the other hand, there was a subtle reduction of
      bacteria growth without differences in the pathology scores in mice infected with
      the laboratory INHr strain. Our results also showed distinct alkyl
      hydroperoxidase C (AhpC) levels in the katG mutant strains, which could explain
      the difference in the virulence profile observed. The difference in the AhpC
      levels between clonal strains was not related to a genetic defect in the gene or
      its promoter. Cumulatively, our results indicate that the virulence, pathology
      and fitness of INHr strains could be negatively affected by multiple mutations in
      katG, lack of the peroxidase activity and reduced AhpC levels.

PMID- 27893798
TI  - Diversity and Impacts of Mining on the Non-Volant Small Mammal Communities of Two
      Vegetation Types in the Brazilian Amazon.
AB  - The Carajas National Forest contains some of the largest iron ore deposits in the
      world. The majority of the minerals are found below a plant community known as
      Savana Metalofila, or "Canga", which represents only 3% of the landscape within
      the Carajas National Forest (CNF). The aim of our study was to understand the
      diversity of community of non-volant small mammals in the two predominant
      vegetation types: Ombrophilous Forest and Canga, and to examine how mining
      impacts these communities. Sampling was conducted from January 2010 to August
      2011 in 11 sampling sites divided by the total area of Canga and 12 sampling
      sites in the forest, totalizing 23 sites. Of these, 12 sites (Canga and Forest)
      were considered impacted areas located close to the mine (<< 900 meters) and 11
      sites (Canga and Forest), serving as controls, which were at least 7,000 meters
      from the mine. We recorded 28 species, 11 from the Order Didelphimorphia and 17
      from the Order Rodentia. The two forest types shared 68.42% of the species found
      in the CNF. A gradient analysis (Non-metric multidimensional scaling) revealed
      that the first axis clearly separated the non-flying small mammal communities by
      vegetation type. Occupancy models showed that the detectability of species was
      affected by the distance from the mining activities. Of all the small mammals
      analyzed, 10 species were positively affected by the distance from mining in
      areas impacted (e.g. more likely to be detected farther from mining areas) and
      detectability was lower in impacted areas. However, three species were negatively
      affected by the distance from mining, with higher detectability in the impacted
      areas, and seven species showed no effect of their proximity to mining
      operations. To date, there are no studies in Brazil about the impact of mining on
      mammals or other vertebrates. This study reveals that the effect of mining may go
      beyond the forest destruction caused by the opening of the mining pits, but also
      may negatively affect sensitive wildlife species.

PMID- 27893797
TI  - Risk Factors for Multiple Organ Dysfunction Syndrome in Severe Stroke Patients.
AB  - BACKGROUND: Severe stroke patients have poor clinical outcome which may be
      associated with development of multiple organ dysfunction syndrome (MODS).
      Therefore, the aim of our study was to investigate independent risk factors for
      development of MODS in severe stroke patients. METHODS: Ninety seven severe
      stroke patients were prospective recruited from Jan 2011 to Jun 2015. The
      development of MODS was identified by Sequential Organ Failure Assessment (SOFA)
      score (score >= 3, at least two organs), which was assessed on day 1, 4, 7, 10
      and 14 after admission. Baseline characteristics, Acute Physiology and Chronic
      Health Evaluation (APACHE) II score, Glasgow coma score (GCS) and cerebral
      imaging parameters were collected at admission. Cox regression was performed to
      determine predictors for the development of MODS. Medical complications after
      admission and in-hospital mortality were also investigated. RESULTS: 33 (34%)
      patients were in MODS group and 64 (66%) were in non-MODS group within 14 days
      after admission. Patients in MODS group had more smoker (51.5% vs 28.1%, p =
      0.023), higher NIHSS score (23.48 +/- 6.12 vs 19.81 +/- 4.83, p = 0.004), higher
      APACHE II score (18.70 +/- 5.18 vs 15.64 +/- 4.36, p = 0.003) and lower GCS score
      (6.33 +/- 2.48 vs 8.14 +/- 2.73, p = 0.002). They also had higher rate of
      infarction in multi vascular territories (36.4% vs 10.9%, p = 0.003). The most
      common complication in all patients was pulmonary infection, while complication
      scores were comparable between two groups. Patients with MODS had higher in
      hospital mortality (69.7% vs 9.4%, p = 0.000). In Cox regression, NIHSS score (RR
      = 1.084, 95% CI 1.019-1.153) and infarction in multi vascular territories (RR =
      2.345 95% CI 1.105-4.978) were independent risk factors for development of MODS.
      CONCLUSIONS: In acute phase of stroke, NIHSS score and infarction in multi
      vascular territories predicted MODS in severe stroke patients. Moreover, patients
      with MODS had higher in-hospital mortality, suggesting that early identification
      of MODS is critical important.

PMID- 27893799
TI  - Tobacco Smoking and Tuberculosis among Men Living with HIV in Johannesburg, South
      Africa: A Case-Control Study.
AB  - SETTING: Although there is ample evidence that smoking increases the risk of
      tuberculosis (TB), the magnitude of impact on TB risk among HIV-infected persons
      is poorly described. Given that a high proportion of patients with TB are co
      infected with HIV in South Africa, the risks arising from the intersection of
      smoking, TB, and HIV/AIDS have key relevance for tobacco control policies.
      OBJECTIVE: To evaluate the association of pulmonary tuberculosis (PTB) with
      current tobacco smoking among men with HIV in South Africa. DESIGN: Case-control
      study of antiretroviral therapy naive men with confirmed HIV-infection in
      Johannesburg. Cases had laboratory-confirmed PTB and controls had no evidence of
      active TB. Participants were interviewed to collect detailed smoking histories.
      RESULTS: We enrolled 146 men diagnosed with PTB and 133 controls. Overall, 33% of
      participants were currently smoking, defined as smoking a cigarette within 2
      months (34% cases vs. 32% controls, p = 0.27). Median CD4 count was lower (60 vs.
      81 cells/mm3, P = 0.03) and median viral load was higher (173 vs. 67 copies/ul
      per thousand, P<0.001) among cases versus controls. In adjusted analyses, current
      smoking tripled the odds of PTB (aOR 3.2; 95%CI: 1.3-7.9, P = 0.01) and former
      smoking nearly doubled the odds of PTB (aOR 1.8; 95%CI 0.8-4.4, P = 0.18)
      compared to never smoking. CONCLUSIONS: Males with HIV that smoke are at greater
      odds for developing PTB than non-smokers. Extensive smoking cessation programs
      are needed to reduce odds of TB and promote health among adults living with HIV.

PMID- 27893800
TI  - NGO Partnerships in Using Ecotourism for Conservation: Systematic Review and Meta
      Analysis.
AB  - We analyse 214 cases worldwide where non-governmental organisations (NGOs) use
      ecotourism for conservation. Other stakeholders in these initiatives include
      local communities, the private sector, and government agencies. Stakeholder
      relationships determine NGO roles and project management structures and
      governance. We classified cases into 10 structural categories based on the
      initiating stakeholder and the NGO role, and used these categories to analyze
      geographic patterns and success factors. Most of the 214 cases are community
      based (~170; 79%); most are in developing countries (190; 89%); and most are in
      protected areas (196; 91%). Frequencies of structural categories differ between
      continents. More cases in Latin America and Asia are initiated by NGOs and local
      communities, and more in Africa by the private sector. Case-study authors used a
      range of economic, socio-cultural and environmental criteria to judge whether
      projects were successful. At global scale, we found no significant association
      between project success and the involvement of private tourism entrepreneurs.
      Projects involving either local or international NGOs had higher success rates
      than those that involved both simultaneously. Future research could adopt
      political ecology approaches to examine: the factors that lead NGOs to adopt
      ecotourism enterprises; their internal decision-making processes and strategies;
      their interactions with the stakeholders involved; and their conservation goals
      and outcomes.

PMID- 27893801
TI  - Pulsatility Index as a Diagnostic Parameter of Reciprocating Wall Shear Stress
      Parameters in Physiological Pulsating Waveforms.
AB  - Arterial wall shear stress (WSS) parameters are widely used for prediction of the
      initiation and development of atherosclerosis and arterial pathologies.
      Traditional clinical evaluation of arterial condition relies on correlations of
      WSS parameters with average flow rate (Q) and heart rate (HR) measurements. We
      show that for pulsating flow waveforms in a straight tube with flow reversals
      that lead to significant reciprocating WSS, the measurements of HR and Q are not
      sufficient for prediction of WSS parameters. Therefore, we suggest adding a third
      quantity-known as the pulsatility index (PI)-which is defined as the peak-to-peak
      flow rate amplitude normalized by Q. We examine several pulsating flow waveforms
      with and without flow reversals using a simulation of a Womersley model in a
      straight rigid tube and validate the simulations through experimental study using
      particle image velocimetry (PIV). The results indicate that clinically relevant
      WSS parameters such as the percentage of negative WSS (P[%]), oscillating shear
      index (OSI) and the ratio of minimum to maximum shear stress rates (min/max), are
      better predicted when the PI is used in conjunction with HR and Q. Therefore, we
      propose to use PI as an additional and essential diagnostic quantity for improved
      predictability of the reciprocating WSS.

PMID- 27893803
TI  - Performance Evaluation Model for Application Layer Firewalls.
AB  - Application layer firewalls protect the trusted area network against information
      security risks. However, firewall performance may affect user experience.
      Therefore, performance analysis plays a significant role in the evaluation of
      application layer firewalls. This paper presents an analytic model of the
      application layer firewall, based on a system analysis to evaluate the capability
      of the firewall. In order to enable users to improve the performance of the
      application layer firewall with limited resources, resource allocation was
      evaluated to obtain the optimal resource allocation scheme in terms of
      throughput, delay, and packet loss rate. The proposed model employs the Erlangian
      queuing model to analyze the performance parameters of the system with regard to
      the three layers (network, transport, and application layers). Then, the analysis
      results of all the layers are combined to obtain the overall system performance
      indicators. A discrete event simulation method was used to evaluate the proposed
      model. Finally, limited service desk resources were allocated to obtain the
      values of the performance indicators under different resource allocation
      scenarios in order to determine the optimal allocation scheme. Under limited
      resource allocation, this scheme enables users to maximize the performance of the
      application layer firewall.

PMID- 27893802
TI  - The Interaction between Zein and Lecithin in Ethanol-Water Solution and
      Characterization of Zein-Lecithin Composite Colloidal Nanoparticles.
AB  - Lecithin, a naturally small molecular surfactant, which is widely used in the
      food industry, can delay aging, enhance memory, prevent and treat diabetes. The
      interaction between zein and soy lecithin with different mass ratios (20:1, 10:1,
      5:1, 3:1, 2:1, 1:1 and 1:2) in ethanol-water solution and characterisation of
      zein and lecithin composite colloidal nanoparticles prepared by antisolvent co
      precipitation method were investigated. The mean size of zein-lecithin composite
      colloidal nanoparticles was firstly increased with the rise of lecithin
      concentration and then siginificantly decreased. The nanoparticles at the zein to
      lecithin mass ratio of 5:1 had the largest particle size (263 nm), indicating
      that zein and lecithin formed composite colloidal nanoparticles, which might
      aggregate due to the enhanced interaction at a higher proportion of lecithin.
      Continuing to increase lecithin concentration, the zein-lecithin nanoparticles
      possibly formed a reverse micelle-like or a vesicle-like structure with zein in
      the core, which prevented the formation of nanoparticle aggregates and decreased
      the size of composite nanoparticles. The presence of lecithin significantly
      reduced the zeta-potential of zein-lecithin composite colloidal nanoparticles.
      The interaction between zein and lecithin enhanced the intensity of the
      fluorescence emission of zein in ethanol-water solution. The secondary structure
      of zein was also changed by the addition of lecithin. Differential scanning
      calorimetry thermograms revealed that the thermal stability of zein-lecithin
      nanoparticles was enhanced with the rise of lecithin level. The composite
      nanoparticles were relatively stable to elevated ionic strengths. Possible
      interaction mechanism between zein and lecithin was proposed. These findings
      would help further understand the theory of the interaction between the alcohol
      soluble protein and the natural small molecular surfactant. The composite
      colloidal nanoparticles formed in this study can broaden the application of zein
      and be suitable for incorporating water-insoluble bioactive components in
      functional food and beverage products.

PMID- 27893804
TI  - TGFbeta Induces Binucleation/Polyploidization in Hepatocytes through a Src
      Dependent Cytokinesis Failure.
AB  - In all mammals, the adult liver shows binucleated as well as mononucleated
      polyploid hepatocytes. The hepatic polyploidization starts after birth with an
      extensive hepatocyte binucleation and generates hepatocytes of several ploidy
      classes. While the functional significance of hepatocyte polyploidy is becoming
      clearer, how it is triggered and maintained needs to be clarified. Aim of this
      study was to identify a major inducer of hepatocyte binucleation/polyploidization
      and the cellular and molecular mechanisms involved. We found that, among several
      cytokines analyzed, known to be involved in early liver development and/or mass
      control, TGFbeta1 was capable to induce, together with the expected morphological
      changes, binucleation in hepatocytes in culture. Most importantly, the
      pharmacological inhibition of TGFbeta signaling in healthy mice during weaning,
      when the physiological binucleation occurs, induced a significant decrease of
      hepatocyte binucleation rate, without affecting cell proliferation and hepatic
      index. The TGFbeta-induced hepatocyte binucleation resulted from a cytokinesis
      failure, as assessed by video microscopy, and is associated with a delocalization
      of the cytokinesis regulator RhoA-GTPase from the mid-body of dividing cells. The
      use of specific chemical inhibitors demonstrated that the observed events are Src
      dependent. Finally, the restoration of a fully epithelial phenotype by TGFbeta
      withdrawal gave rise to a cell progeny capable to maintain the polyploid state.
      In conclusion, we identified TGFbeta as a major inducer of hepatocyte
      binucleation both in vitro and in vivo, thus ascribing a novel role to this
      pleiotropic cytokine. The production of binucleated/tetraploid hepatocytes is due
      to a cytokinesis failure controlled by the molecular axis TGFbeta/Src/RhoA.

PMID- 27893805
TI  - Association between Alcohol Intake and Hemoglobin A1c in the Korean Adults: The
      2011-2013 Korea National Health and Nutrition Examination Survey.
AB  - BACKGROUND: Although alcohol consumption is commonly encountered in clinical
      practice, few studies have investigated the clinical significance of alcohol
      intake on the use of the hemoglobin A1c (HbA1c) level. OBJECTIVES: This study was
      performed to investigate the association between alcohol intake and HbA1c level
      in the general population. METHODS: Among the 24,594 participants who
      participated in the 2011-2013 Korea National Health and Nutrition Examination
      Survey (KNHANES), 12,923 participants were analyzed in this study. We excluded
      diabetic patients currently taking antidiabetes medication. We compared the HbA1c
      level and proportions of patients with an HbA1c level of >=5.7%, >=6.1%, and
      >=6.5% according to the fasting plasma glucose (FPG) concentration range and the
      amount of alcohol intake. The average amounts of daily alcohol intake were
      categorized into three groups: 0 g/day, <30 g/day, >=30 g/day. RESULTS: The mean
      HbA1c level was 5.65%, and the mean FPG concentration was 95.3 mg/dl. The
      percentages of patients with an HbA1c level of >=5.7%, >=6.1%, and >=6.5% were
      42.6%, 13.4%, and 4.5%, respectively. The average amount of alcohol intake was
      12.3 g/day. The percentages of subjects with alcohol intake 0, <30, and >= 30
      g/day were 16.5%, 69.7%, and 13.8%, respectively. There was a significant
      positive relationship between alcohol intake and FPG concentration (P < 0.001),
      the prevalence of impaired fasting glucose (P < 0.001), and the prevalence of
      diabetes (P < 0.001). However, there was no significant relationship between the
      alcohol intake and HbA1c level. Overall, the adjusted HbA1c levels decreased
      across alcohol intake (5.70% +/- 0.01%, 5.66% +/- 0.01%, and 5.55% +/- 0.01%)
      after adjustment for confounding factors such as age, sex, FPG concentration,
      college graduation, smoking history, presence of hypertension, waist
      circumference, serum total cholesterol concentration, serum high-density
      lipoprotein cholesterol concentration, serum triglyceride concentration, presence
      of anemia, serum white blood cell count, and serum alanine aminotransferase
      concentration (P < 0.001). The adjusted proportions (%) of patients with an HbA1c
      level of >=5.7% (P < 0.001), >=6.1% (P < 0.001), and >=6.5% (P < 0.001) showed
      significant negative trends across alcohol intake after adjustment for
      confounders. Logistic regression analyses showed that, when using the group that
      abstained as the control, the group that consumed >= 30g/day was negatively
      associated with the risk of an HbA1c level of >=5.7% (P < 0.001), >=6.1% (P <
      0.001), and >=6.5% (P < 0.001), using the above-mentioned variables as
      covariates. CONCLUSIONS: Higher alcohol intake was associated with lower HbA1c
      levels, even after adjusting for confounding factors, including the FPG
      concentration, in this nationally representative sample of Korean adults. These
      results suggest that excessive drinking shifts the HbA1c level downward, which
      might complicate use of the HbA1c level for the diagnosis of diabetes or
      prediabetes.

PMID- 27893806
TI  - HPLC-Based Mass Spectrometry Characterizes the Phospholipid Alterations in Ether
      Linked Lipid Deficiency Models Following Oxidative Stress.
AB  - Despite the fact that the discovery of ether-linked phospholipids occurred nearly
      a century ago, many unanswered questions remain concerning these unique lipids.
      Here, we characterize the ether-linked lipids of the nematode with HPLC-MS/MS and
      find that more than half of the phosphoethanolamine-containing lipids are ether
      linked, a distribution similar to that found in mammalian membranes. To explore
      the biological role of ether lipids in vivo, we target fatty acyl-CoA reductase
      (fard-1), an essential enzyme in ether lipid synthesis, with two distinct RNAi
      strategies. First, when fard-1 RNAi is initiated at the start of development, the
      treated animals have severely reduced ether lipid abundance, resulting in a shift
      in the phosphatidylethanolamine lipid population to include more saturated fatty
      acid chains. Thus, the absence of ether lipids during development drives a
      significant remodeling of the membrane landscape. A later initiation of fard-1
      RNAi in adulthood results in a dramatic reduction of new ether lipid synthesis as
      quantified with 15N-tracers; however, there is only a slight decrease in total
      ether lipid abundance with this adult-only fard-1 RNAi. The two RNAi strategies
      permit the examination of synthesis and ether lipid abundance to reveal a
      relationship between the amount of ether lipids and stress survival. We tested
      whether these species function as sacrificial antioxidants by directly examining
      the phospholipid population with HPLC-MS/MS after oxidative stress treatment.
      While there are significant changes in other phospholipids, including
      polyunsaturated fatty acid-containing species, we did not find any change in
      ether-linked lipids, suggesting that the role of ether lipids in stress
      resistance is not through their general consumption as free radical sinks. Our
      work shows that the nematode will be a useful model for future interrogation of
      ether lipid biosynthesis and the characterization of phospholipid changes in
      various stress conditions.

PMID- 27893807
TI  - ERP Response Unveils Effect of Second Language Manipulation on First Language
      Processing.
AB  - Lexical access in bilinguals has been considered either selective or non
      selective and evidence exists in favor of both hypotheses. We conducted a
      linguistic experiment to assess whether a bilingual's language mode influences
      the processing of first language information. We recorded event related
      potentials during a semantic priming paradigm with a covert manipulation of the
      second language (L2) using two types of stimulus presentations (short and long).
      We observed a significant facilitation of word pairs related in L2 in the short
      version reflected by a decrease in N400 amplitude in response to target words
      related to the English meaning of an inter-lingual homograph (homograph-unrelated
      group). This was absent in the long version, as the N400 amplitude for this group
      was similar to the one for the control-unrelated group. We also interviewed the
      participants whether they were aware of the importance of L2 in the experiment.
      We conclude that subjects participating in the long and short versions were in
      different language modes: closer to monolingual mode for the long and closer to
      bilingual mode for the short version; and that awareness about covert
      manipulation of L2 can influence the language mode, which in its turn influences
      the processing of the first language.

PMID- 27893809
TI  - Model of Selective and Non-Selective Management of Badgers (Meles meles) to
      Control Bovine Tuberculosis in Badgers and Cattle.
AB  - Bovine tuberculosis (bTB) causes substantial economic losses to cattle farmers
      and taxpayers in the British Isles. Disease management in cattle is complicated
      by the role of the European badger (Meles meles) as a host of the infection.
      Proactive, non-selective culling of badgers can reduce the incidence of disease
      in cattle but may also have negative effects in the area surrounding culls that
      have been associated with social perturbation of badger populations. The
      selective removal of infected badgers would, in principle, reduce the number
      culled, but the effects of selective culling on social perturbation and disease
      outcomes are unclear. We used an established model to simulate non-selective
      badger culling, non-selective badger vaccination and a selective trap and
      vaccinate or remove (TVR) approach to badger management in two distinct areas:
      South West England and Northern Ireland. TVR was simulated with and without
      social perturbation in effect. The lower badger density in Northern Ireland
      caused no qualitative change in the effect of management strategies on badgers,
      although the absolute number of infected badgers was lower in all cases. However,
      probably due to differing herd density in Northern Ireland, the simulated badger
      management strategies caused greater variation in subsequent cattle bTB
      incidence. Selective culling in the model reduced the number of badgers killed by
      about 83% but this only led to an overall benefit for cattle TB incidence if
      there was no social perturbation of badgers. We conclude that the likely benefit
      of selective culling will be dependent on the social responses of badgers to
      intervention but that other population factors including badger and cattle
      density had little effect on the relative benefits of selective culling compared
      to other methods, and that this may also be the case for disease management in
      other wild host populations.

PMID- 27893808
TI  - Common Polymorphisms in the 5-Lipoxygenase Pathway and Risk of Incident
      Myocardial Infarction: A Danish Case-Cohort Study.
AB  - BACKGROUND: The 5-lipoxygenase pathway (5-LOX) has been implicated in the
      development of cardiovascular disease and studies have suggested that genetic
      polymorphisms related to key enzymes in this pathway may confer risk of
      myocardial infarction (MI). This study investigated the association of pre
      selected genetic polymorphisms in four candidate genes of 5-LOX (arachidonate 5
      lipoxygenase and its activating protein (ALOX-5 and FLAP), leukotriene A4
      hydroxylase (LTA4-H) and leukotriene C4 synthase (LTC4-S)) with incident MI.
      METHODS: In a Danish cohort including 57,053 participants, aged 50-64 at
      enrolment and recruited from 1993-97, we conducted a case-cohort study including
      cases with incident MI and a randomly selected sub cohort of 3,000 participants.
      Cases were identified from national registries through July 2013. A total of 22
      SNPs were selected and genotyped using the commercially available KASPTM assay. A
      tandem-repeat polymorphism, located in the ALOX-5 gene, was genotyped by multi
      titre plate sequencing. Haplotypes were inferred using PHASE 2.1. RESULTS: During
      a median follow-up of 17.0 years we identified 3,089 cases of incident MI. In
      FLAP, two SNPs were negatively associated with incident MI (rs9551963 &
      rs17222842) while one SNP (rs2247570) located in LTA4-H, was associated with
      higher risk of MI when comparing subjects with two copies of the variant allele
      to homozygotes for the wild type. However, only rs17222842 remained significantly
      associated with MI after correcting for multiple testing. Furthermore, the
      promoter polymorphism rs59439148 was associated with risk of MI in men. For male
      carriers of two variant alleles we found a hazard ratio of 1.63 (95% CI:
      1.06;2.52) compared to homozygotes for the wild type. Previously described
      haplotypes (Hap-A -B, -E and -K) were not associated with MI in our population.
      CONCLUSION: In conclusion, some common polymorphisms in the 5-lipoxygenase
      pathway were modestly associated with incident MI, suggesting a potential role
      for this pathway in the development of cardiovascular disease.

PMID- 27893810
TI  - Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A
      Virus Infection.
AB  - Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can
      cause mild to severe illness and potentially death. Antiviral drugs are an
      important countermeasure against IAV; however, drug resistance has developed,
      thus new therapeutic approaches are being sought. Previously, we demonstrated the
      antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to
      reduce influenza replication in vitro and pulmonary virus burden in mice. In this
      study, in vivo efficacy of verdinexor was further evaluated in two animal models
      or influenza virus infection, mice and ferrets. In mice, verdinexor was
      efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine
      expression, and moderate leukocyte infiltration into the bronchoalveolar space.
      Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden,
      and inflammatory cytokine expression in the nasal wash exudate. These findings
      support the anti-viral efficacy of verdinexor, and warrant its development as a
      novel antiviral therapeutic for influenza infection.

PMID- 27893812
TI  - Solid-Phase Synthesis of ?-Lactone and 1,2-Oxazine Derivatives and Their
      Efficient Chiral Analysis.
AB  - Derivatives of 3-methyl-3,6-dihydro-2H-1,2-oxazine-6-carboxylic acid prepared by
      regioselective hetero Diels-Alder reaction of arylnitroso compounds with sorbic
      acid were used for solid-phase synthesis of a library of derivatives that
      included modification of carboxylic group, dihydroxylation of double bond and
      cleavage of N-O bond. Derivatives of 2,3,4-trihydroxyhexanoic acid obtained from
      3,6-dihydro-2H-1,2-oxazines after double bond dihydroxylation and N-O cleavage
      were used for simple and stereoselective formation of chiral lactones derived
      from 3,4-dihydroxydihydrofuran-2(3H)-one. The final compounds obtained as a
      mixture of stereoisomers were analyzed with use of chiral HPLC and SFC. HPLC
      analyses were not successful for all derivatives or required lengthy
      chromatography. On the other hand SFC afforded much shorter analyses and was
      effective for all studied derivatives. The method of synthesis and analysis is
      thus suitable for future study of stereoselective synthesis of lactones and other
      derivatives from single oxazine derivatives and application of high-throughput
      synthesis on solid-support and combinatorial chemistry.

PMID- 27893811
TI  - The Inhibition of microRNA-128 on IGF-1-Activating mTOR Signaling Involves in
      Temozolomide-Induced Glioma Cell Apoptotic Death.
AB  - Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a
      first-line chemotherapeutic drug used in the clinical therapy of glioblastoma
      multiforme, the most common and high-grade primary glioma in adults. Micro
      (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene
      expressions and are involved in gliomagenesis. However, no studies have reported
      relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated
      miRNA profiles and its molecular mechanisms underlying the induction of glioma
      cell death. By performing miRNA microarray and bioinformatics analyses, we
      observed that expression of 248 miRNAs was altered, including five significantly
      upregulated and 17 significantly downregulated miRNAs, in TMZ-treated U87MG
      cells. miR-128 expression levels were lower in different glioma cells and
      strongly associated with poor survival. TMZ treatment significantly upregulated
      miR-128 expression. TMZ significantly enhanced miR-128-1 promoter activity and
      transcriptionally regulated miR-128 levels through c-Jun N-terminal kinase 2/c
      Jun pathways. The overexpression and knockdown of miR-128 expression
      significantly affected TMZ-mediated cell viability and apoptosis-related protein
      expression. Furthermore, the overexpression of miR-128 alone enhanced apoptotic
      death of glioma cells through caspase-3/9 activation, poly(ADP ribose) polymerase
      degradation, reactive oxygen species generation, mitochondrial membrane potential
      loss, and non-protective autophagy formation. Finally, we identified that key
      members in mammalian target of rapamycin (mTOR) signaling including mTOR,
      rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and
      PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR
      signaling through miR-128 regulation. These results indicate that miR-128
      inhibited mTOR signaling is involved in TMZ-mediated cytotoxicity. Our findings
      may provide a better understanding of cytotoxic mechanisms of TMZ involved in
      glioblastoma development.

PMID- 27893814
TI  - Rapid Top-Down Control of Behavior Due to Propositional Knowledge in Human
      Associative Learning.
AB  - Propositional and associative processes have been proposed to explain human
      associative learning. Our main objective in this study was to evaluate whether
      propositional knowledge may gain control over behavior even under high time
      pressure conditions, as suggested by propositional single-process models. In the
      experiment reported, different groups of participants had to learn a series of
      cue-outcome relationships on a trial-by-trial basis under different time pressure
      conditions. Later, a simple verbal instruction indicated that one of the cues had
      reversed its contingency (informed condition). The other cue had also changed its
      contingency, though in an unanticipated way (uninformed condition) whilst other
      contingencies did not change (no-change condition). The results showed that, in
      the absence of instructions, interference (i.e., uninformed vs. no-change effect)
      was greater in the high time than in the low time-pressure group. This result
      indicates that those responses which were previously relevant are more difficult
      to inhibit when there is little time to respond. However, time pressure had no
      detectable effect on the use of the verbal instruction, since an equivalent
      instruction advantage (i.e., uninformed vs. informed effect) was obtained in both
      time pressure groups. These results reveal that propositional knowledge can
      override those cue-outcome relationships that were learnt trial-by-trial even
      under conditions of high cognitive demand. This pattern of results is consistent
      with a propositional single-process model of associative learning.

PMID- 27893813
TI  - Azidothymidine Sensitizes Primary Effusion Lymphoma Cells to Kaposi Sarcoma
      Associated Herpesvirus-Specific CD4+ T Cell Control and Inhibits vIRF3 Function.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) is linked with the development of
      Kaposi sarcoma and the B lymphocyte disorders primary effusion lymphoma (PEL) and
      multi-centric Castleman disease. T cell immunity limits KSHV infection and
      disease, however the virus employs multiple mechanisms to inhibit efficient
      control by these effectors. Thus KSHV-specific CD4+ T cells poorly recognize most
      PEL cells and even where they can, they are unable to kill them. To make KSHV
      infected cells more sensitive to T cell control we treated PEL cells with the
      thymidine analogue azidothymidine (AZT), which sensitizes PEL lines to Fas-ligand
      and TRAIL challenge; effector mechanisms which T cells use. PELs co-cultured with
      KSHV-specific CD4+ T cells in the absence of AZT showed no control of PEL
      outgrowth. However in the presence of AZT PEL outgrowth was controlled in an MHC
      restricted manner. To investigate how AZT sensitizes PELs to immune control we
      first examined BJAB cells transduced with individual KSHV-latent genes for their
      ability to resist apoptosis mediated by stimuli delivered through Fas and TRAIL
      receptors. This showed that in addition to the previously described vFLIP
      protein, expression of vIRF3 also inhibited apoptosis delivered by these stimuli.
      Importantly vIRF3 mediated protection from these apoptotic stimuli was inhibited
      in the presence of AZT as was a second vIRF3 associated phenotype, the
      downregulation of surface MHC class II. Although both vFLIP and vIRF3 are
      expressed in PELs, we propose that inhibiting vIRF3 function with AZT may be
      sufficient to restore T cell control of these tumor cells.

PMID- 27893817
TI  - The Impact of Group Size on Welfare Indicators of Ewes during Pregnancy.
AB  - Group size (GS) and space allowance have major implications for the welfare of
      production species, however their effects are often confounded. In a previous
      study we investigated the impact of varying space allowance at constant GS. In
      the present work we report the consequences of varying GS on pregnant ewes while
      controlling space allowance. We housed ewes at 6 (GS6) or 12 ewes/enclosure
      (GS12), while controlling space allowance to 1.5 m2/ewe (3 enclosures/treatment),
      and necessarily varying enclosure size. Therefore, when indicating GS effects we
      implicitly reflect a confounding effect with that of enclosure size. Movement,
      use of space, behaviour, serum cortisol concentration and body condition score
      (BCS) were collected during the last 12 gestation weeks. Movement, use of space,
      and behaviour were collected every other week, during 2 days/week, using 10
      minute continuous scan samplings. Blood was collected during weeks 10, 13, 17,
      and 21 of gestation, and BCS during weeks 15 and 21. Data were analysed using
      repeated measures, generalized linear mixed models, with GS, week, and their
      interaction as fixed effects, and enclosure as random effect. GS mainly affected
      movement and use of space. GS12 ewes walked longer distances using longer steps
      (P<0.001). An interaction GS by week was observed for angular dispersion
      (P<0.0001), which was smaller for GS12 from week 10 onwards. Initial restlessness
      levels were lower for GS12, as shown by the reduced frequency of location changes
      (P<0.0001). Furthest and mean neighbour distances increased with GS (P<0.0001).
      The effect of GS on behaviour was only evident for eating behaviour as an
      interaction with gestation week (P<0.05). Changes in behaviour, movement and use
      of space along the study indicated an activity peak during weeks 3 to 5. Cortisol
      changes during gestation (P<0.01) also reflected this activity peak, while BCS
      (P<0.001) reflected normal physical condition changes during pregnancy. Although
      the separate effects of GS and enclosure size cannot be disentangled, we conclude
      that if enough space/ewe is given during gestation, larger GS will result in
      larger effective space, and no major implications for the welfare of ewes should
      be expected as GS increases. Ewes will adapt their movement patterns and use of
      space to enclosure size, and no further behavioural, physiological and physical
      consequences should be expected.

PMID- 27893815
TI  - An Accessory Protease Inhibitor to Increase the Yield and Quality of a Tumour
      Targeting mAb in Nicotiana benthamiana Leaves.
AB  - The overall quality of recombinant IgG antibodies in plants is dramatically
      compromised by host endogenous proteases. Different approaches have been
      developed to reduce the impact of endogenous proteolysis on IgGs, notably
      involving site-directed mutagenesis to eliminate protease-susceptible sites or
      the in situ mitigation of host protease activities to minimize antibody
      processing in the cell secretory pathway. We here characterized the degradation
      profile of H10, a human tumour-targeting monoclonal IgG, in leaves of Nicotiana
      benthamiana also expressing the human serine protease inhibitor alpha1
      antichymotrypsin or the cysteine protease inhibitor tomato cystatin SlCYS8. Leaf
      extracts revealed consistent fragmentation patterns for the recombinant antibody
      regardless of leaf age and a strong protective effect of SlCYS8 in specific
      regions of the heavy chain domains. As shown using an antigen-binding ELISA and
      LC-MS/MS analysis of antibody fragments, SlCYS8 had positive effects on both the
      amount of fully-assembled antibody purified from leaf tissue and the stability of
      biologically active antibody fragments containing the heavy chain Fc domain. Our
      data confirm the potential of Cys protease inhibitors as convenient antibody
      stabilizing expression partners to increase the quality of therapeutic antibodies
      in plant protein biofactories.

PMID- 27893818
TI  - Trends in Irritable Bowel Syndrome Incidence among Taiwanese Adults during 2003
      2013: A Population-Based Study of Sex and Age Differences.
AB  - BACKGROUND: No population-based irritable bowel syndrome (IBS) incidence data
      among Taiwanese adults are available. Whether IBS is associated with risk of
      organic colonic diseases remains unanswered. We investigated 1) the sex- and age
      stratified trends in the annual incidence of IBS, and 2) the risk of selected
      organic diseases in patients with IBS compared with those without IBS among
      Taiwanese adults during 2003-2013. METHODS: Medical claims data for 1 million
      randomly selected beneficiaries were obtained and analyzed. Patients with IBS
      were considered eligible for enrollment if they aged between 20 and 100 and had
      at least two medical encounters with IBS codes within 1 year. To test whether
      there was a linear secular trend in IBS incidence over time, multivariate Poisson
      regression with generalized estimating equation model was conducted. The risk of
      selected organic diseases associated with IBS was examined using multivariate Cox
      proportional hazard regression. RESULTS: From 2003 to 2013, the incidence of IBS
      significantly decreased over time [adjusted incidence rate ratio (IRR) = 0.97, p<
      0.001]; the incidence of IBS significantly increased with age (adjusted IRR =
      1.03, p < 0.001) and was significantly higher in women than in men (adjusted IRR
      = 1.14, p< 0.001). IBS significantly associated with increased risk of
      microscopic colitis, inflammatory bowel disease, and colorectal cancer during a
      10-year follow-up period. CONCLUSIONS: The incidence of IBS increased with age
      and was slightly higher in women than in men among Taiwanese adults. During 2003
      2013, IBS incidence gradually decreased over time. IBS may increase risk of
      several colonic organic diseases.

PMID- 27893816
TI  - miR-34 Modulates Innate Immunity and Ecdysone Signaling in Drosophila.
AB  - microRNAs are endogenous small regulatory RNAs that modulate myriad biological
      processes by repressing target gene expression in a sequence-specific manner.
      Here we show that the conserved miRNA miR-34 regulates innate immunity and
      ecdysone signaling in Drosophila. miR-34 over-expression activates antibacterial
      innate immunity signaling both in cultured cells and in vivo, and flies over
      expressing miR-34 display improved survival and pathogen clearance upon Gram
      negative bacterial infection; whereas miR-34 knockout animals are defective in
      antibacterial defense. In particular, miR-34 achieves its immune-stimulatory
      function, at least in part, by repressing the two novel target genes Dlg1 and
      Eip75B. In addition, our study reveals a mutual repression between miR-34
      expression and ecdysone signaling, and identifies miR-34 as a node in the
      intricate interplay between ecdysone signaling and innate immunity. Lastly, we
      identify cis-regulatory genomic elements and trans-acting transcription factors
      required for optimal ecdysone-mediated repression of miR-34. Taken together, our
      study enriches the repertoire of immune-modulating miRNAs in animals, and
      provides new insights into the interplay between steroid hormone signaling and
      innate immunity.

PMID- 27893819
TI  - Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4
      Signaling Pathway after Pressure Overload in Mice.
AB  - BACKGROUND: Heart failure(HF) is a dangerous disease that affects millions of
      patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases.
      Salvianolic acid B(SalB) is the major active component of Radix Salvia. This
      study investigated the mechanisms of action and effects of SalB on HF in an
      experimental mouse model of HF. METHODS: We created a mouse model of HF by
      inducing pressure overload with transverse aortic constriction(TAC) surgery for 2
      weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9),
      TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group
      (SalB, 240 mg*kg-1*day-1, n = 9). Echocardiography was used to evaluate the
      dynamic changes in cardiac structure and function in vivo. Plasma brain
      natriuretic peptide (BNP) concentration was detected by Elisa method. In
      addition, H9C2 rat cardiomyocytes were cultured and Western blot were implemented
      to evaluate the phosphorylation of ERK1/2, AKT, and protein expression of GATA4.
      RESULTS: SalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites
      of ERK1/2, but not Ser473 site of AKT, subsequently inhibited protein expression
      of GATA4 and plasma BNP(P < 0.001), and then inhibited HF at 2 weeks after TAC
      surgery. CONCLUSIONS: Our data provide a mechanism of inactivating the
      ERK1/2/GATA4 signaling pathway for SalB inhibition of the TAC-induced HF.

PMID- 27893821
TI  - Feature Selection Using Information Gain for Improved Structural-Based Alert
      Correlation.
AB  - Grouping and clustering alerts for intrusion detection based on the similarity of
      features is referred to as structurally base alert correlation and can discover a
      list of attack steps. Previous researchers selected different features and data
      sources manually based on their knowledge and experience, which lead to the less
      accurate identification of attack steps and inconsistent performance of
      clustering accuracy. Furthermore, the existing alert correlation systems deal
      with a huge amount of data that contains null values, incomplete information, and
      irrelevant features causing the analysis of the alerts to be tedious, time
      consuming and error-prone. Therefore, this paper focuses on selecting accurate
      and significant features of alerts that are appropriate to represent the attack
      steps, thus, enhancing the structural-based alert correlation model. A two-tier
      feature selection method is proposed to obtain the significant features. The
      first tier aims at ranking the subset of features based on high information gain
      entropy in decreasing order. The? second tier extends additional features with a
      better discriminative ability than the initially ranked features. Performance
      analysis results show the significance of the selected features in terms of the
      clustering accuracy using 2000 DARPA intrusion detection scenario-specific
      dataset.

PMID- 27893820
TI  - Azithromycin vs. Placebo for the Clinical Outcome in Campylobacter concisus
      Diarrhoea in Adults: A Randomized, Double-Blinded, Placebo-Controlled Clinical
      Trial.
AB  - : Campylobacter concisus has been associated with prolonged mild diarrhoea, but
      investigations regarding the efficacy of antimicrobial treatment have not been
      reported previously. We initiated a phase 3, single-centre, randomized, double
      blinded, placebo-controlled study comparing the efficacy of 500 mg once-daily
      dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for
      the treatment of C. concisus diarrhoea in adult patients with a follow-up period
      of ten days. If symptoms persisted at day ten, the patient was offered cross-over
      study treatment of three days and another ten-day follow-up period. The primary
      efficacy endpoint was the clinical response, defined as time to cessation of
      diarrhoea (<3 stools/day or reversal of accompanying symptoms). Our estimated
      sample size was 100 patients. We investigated a total of 10,036 diarrheic stool
      samples from 7,089 adult patients. Five-hundred and eighty-eight C. concisus
      positive patients were assessed for eligibility, of which 559 were excluded prior
      to randomization. The three main reasons for exclusion were duration of diarrhoea
      longer than 21 days (n = 124), previous antibiotic treatment (n = 113), and co
      pathogens in stools (n = 87). Therefore, 24 patients completed the trial with
      either azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms
      of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16-19). One
      person in the azithromycin group and four from the placebo group chose to
      continue with crossover medication after the initial ten-day period. In the
      azithromycin group, there was a mean of seven days (95% CI: 5-9) to clinical cure
      and for the placebo group it was ten days (95% CI: 6-14) (OR-3 (95% CI: -7-1). We
      observed no differences in all examined outcomes between azithromycin treatment
      and placebo. However, due to unforeseen recruitment difficulties we did not reach
      our estimated sample size of 100 patients and statistical power to conclude on an
      effect of azithromycin treatment was not obtained. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT01531218.

PMID- 27893822
TI  - Deciphering Multiplicity of HIV-1C Infection: Transmission of Closely Related
      Multiple Viral Lineages.
AB  - BACKGROUND: A single viral variant is transmitted in the majority of HIV
      infections. However, about 20% of heterosexually transmitted HIV infections are
      caused by multiple viral variants. Detection of transmitted HIV variants is not
      trivial, as it involves analysis of multiple viral sequences representing intra
      host HIV-1 quasispecies. METHODOLOGY: We distinguish two types of multiple virus
      transmission in HIV infection: (1) HIV transmission from the same source, and (2)
      transmission from different sources. Viral sequences representing intra-host
      quasispecies in a longitudinally sampled cohort of 42 individuals with primary
      HIV-1C infection in Botswana were generated by single-genome amplification and
      sequencing and spanned the V1C5 region of HIV-1C env gp120. The Maximum
      Likelihood phylogeny and distribution of pairwise raw distances were assessed at
      each sampling time point (n = 217; 42 patients; median 5 (IQR: 4-6) time points
      per patient, range 2-12 time points per patient). RESULTS: Transmission of
      multiple viral variants from the same source (likely from the partner with
      established HIV infection) was found in 9 out of 42 individuals (21%; 95 CI 10
      37%). HIV super-infection was identified in 2 patients (5%; 95% CI 1-17%) with an
      estimated rate of 3.9 per 100 person-years. Transmission of multiple viruses
      combined with HIV super-infection at a later time point was observed in one
      individual. CONCLUSIONS: Multiple HIV lineages transmitted from the same source
      produce a monophyletic clade in the inferred phylogenetic tree. Such a clade has
      transiently distinct sub-clusters in the early stage of HIV infection, and
      follows a predictable evolutionary pathway. Over time, the gap between initially
      distinct viral lineages fills in and initially distinct sub-clusters converge.
      Identification of cases with transmission of multiple viral lineages from the
      same source needs to be taken into account in cross-sectional estimation of HIV
      recency in epidemiological and population studies.

PMID- 27893823
TI  - Shared Decision Making at the Limit of Viability: A Blueprint for Physician
      Action.
AB  - OBJECTIVE: To document interactions during the antenatal consultation between
      parents and neonatologist that parents linked to their satisfaction with their
      participation in shared decision making for their infant at risk of being born at
      the limit of viability. METHODS: This multiple-case ethnomethodological
      qualitative research study, included mothers admitted for a threatened premature
      delivery between 200/7 and 266/7 weeks gestation, the father, and the staff
      neonatologist conducting the clinical antenatal consultation. Content analysis of
      an audiotaped post-antenatal consultation interview with parents obtained their
      satisfaction scores as well as their comments on physician actions that
      facilitated their desired participation. RESULTS: Five cases, each called a
      "system-infant at risk", included 10 parents and 6 neonatologists. From the
      interviews emerged a blueprint for action by physicians, including communication
      strategies that parents say facilitated their participation in decision making;
      such as building trustworthy physician-parent relationships, providing "balanced"
      information, offering choices, and allowing time to think. CONCLUSION: Parent
      descriptions indicate that the opportunity to participate to their satisfaction
      in the clinical antenatal consultation depends on how the physician interacts
      with them. PRACTICE IMPLICATIONS: The parent-identified communication strategies
      facilitate shared decision making regarding treatment in the best interest of the
      infant at risk to be born at the limit of viability.

PMID- 27893824
TI  - Analysis of Synonymous Codon Usage Bias of Zika Virus and Its Adaption to the
      Hosts.
AB  - Zika virus (ZIKV) is a mosquito-borne virus (arbovirus) in the family
      Flaviviridae, and the symptoms caused by ZIKV infection in humans include rash,
      fever, arthralgia, myalgia, asthenia and conjunctivitis. Codon usage bias
      analysis can reveal much about the molecular evolution and host adaption of ZIKV.
      To gain insight into the evolutionary characteristics of ZIKV, we performed a
      comprehensive analysis on the codon usage pattern in 46 ZIKV strains by
      calculating the effective number of codons (ENc), codon adaptation index (CAI),
      relative synonymous codon usage (RSCU), and other indicators. The results
      indicate that the codon usage bias of ZIKV is relatively low. Several lines of
      evidence support the hypothesis that translational selection plays a role in
      shaping the codon usage pattern of ZIKV. The results from a correspondence
      analysis (CA) indicate that other factors, such as base composition, aromaticity,
      and hydrophobicity may also be involved in shaping the codon usage pattern of
      ZIKV. Additionally, the results from a comparative analysis of RSCU between ZIKV
      and its hosts suggest that ZIKV tends to evolve codon usage patterns that are
      comparable to those of its hosts. Moreover, selection pressure from Homo sapiens
      on the ZIKV RSCU patterns was found to be dominant compared with that from Aedes
      aegypti and Aedes albopictus. Taken together, both natural translational
      selection and mutation pressure are important for shaping the codon usage pattern
      of ZIKV. Our findings contribute to understanding the evolution of ZIKV and its
      adaption to its hosts.

PMID- 27893826
TI  - Macro-Scale Patterns in Upwelling/Downwelling Activity at North American West
      Coast.
AB  - The seasonal and interannual variability of vertical transport
      (upwelling/downwelling) has been relatively well studied, mainly for the
      California Current System, including low-frequency changes and latitudinal
      heterogeneity. The aim of this work was to identify potentially predictable
      patterns in upwelling/downwelling activity along the North American west coast
      and discuss their plausible mechanisms. To this purpose we applied the min/max
      Autocorrelation Factor technique and time series analysis. We found that spatial
      co-variation of seawater vertical movements present three dominant low-frequency
      signals in the range of 33, 19 and 11 years, resembling periodicities of:
      atmospheric circulation, nodal moon tides and solar activity. Those periodicities
      might be related to the variability of vertical transport through their influence
      on dominant wind patterns, the position/intensity of pressure centers and the
      strength of atmospheric circulation cells (wind stress). The low-frequency
      signals identified in upwelling/downwelling are coherent with temporal patterns
      previously reported at the study region: sea surface temperature along the
      Pacific coast of North America, catch fluctuations of anchovy Engraulis mordax
      and sardine Sardinops sagax, the Pacific Decadal Oscillation, changes in
      abundance and distribution of salmon populations, and variations in the position
      and intensity of the Aleutian low. Since the vertical transport is an
      oceanographic process with strong biological relevance, the recognition of their
      spatio-temporal patterns might allow for some reasonable forecasting capacity,
      potentially useful for marine resources management of the region.

PMID- 27893825
TI  - Low Birth Weight Is Associated with a Decreased Overall Adult Health Status and
      Reproductive Capability - Results of a Cross-Sectional Study in Primary Infertile
      Patients.
AB  - Individuals born with low birth weight (LBW) risk cardiometabolic complications
      later in life. However the impact of LBW on general health status and male
      reproductive function has been scantly analysed. We investigated the clinical and
      seminal impact of different birth weights (BW) in white-European men presenting
      for primary couple's infertility. Demographic, clinical, and laboratory data from
      827 primary infertile men were compared with those of 373 consecutive fertile
      men. Patients with BW <=2500, 2500-4200, and >=4200gr were classified as having
      LBW, normal (NBW), and high BW (HBW), respectively. Health-significant
      comorbidities were scored with the Charlson Comorbidity Index (CCI). Testicular
      volume was assessed with a Prader orchidometer. Semen analysis values were
      assessed based on 2010 WHO reference criteria. Descriptive statistics and
      regression models tested associations between semen parameters, clinical
      characteristics and BW categories. LBW, NBW and HBW were found in 71 (8.6%), 651
      (78.7%) and 105 (12.7%) infertile men, respectively. LBW was more frequent in
      infertile patients than fertile men (p = 0.002). Infertile patients with LBW had
      a higher rate of comorbidities (p = 0.003), lower mean testicular volume (p =
      0.007), higher FSH (p = 0.02) and lower tT levels (p = 0.04) compared to other BW
      groups. Higher rates of asthenozoospermia (p = 0.02) and teratozoospermia (p =
      0.03) were also found in LBW men. At logistic regression models, LBW was
      univariably associated with pathologic progressive motility (p<=0.02) and
      pathologic sperm morphology (p<0.005). At multivariable logistic regression
      analysis, LBW achieved independent predictor status for both lower sperm motility
      and pathologic sperm morphology (all p<=0.04). Only LBW independently predicted
      higher CCI values (p<0.001). In conclusion, we found that LBW was more frequent
      in infertile than in fertile men. Infertile individuals with LBW showed a higher
      rate of comorbidities and significantly worse clinical, endocrine and semen
      parameters compared to other BW groups.

PMID- 27893828
TI  - A Novel Large-Scale Temperature Dominated Model for Predicting the End of the
      Growing Season.
AB  - Vegetation phenology regulates many ecosystem processes and is an indicator of
      the biological responses to climate change. It is important to model the timing
      of leaf senescence accurately, since the canopy duration and carbon assimilation
      are strongly determined by the timings of leaf senescence. However, the existing
      phenology models are unlikely to accurately predict the end of the growing season
      (EGS) on large scales, resulting in the misrepresentation of the seasonality and
      interannual variability of biosphere-atmosphere feedbacks and interactions in
      coupled global climate models. In this paper, we presented a novel large-scale
      temperature dominated model integrated with the physiological adaptation of
      plants to the local temperature to assess the spatial pattern and interannual
      variability of the EGS. Our model was validated in all temperate vegetation types
      over the Northern Hemisphere. The results indicated that our model showed better
      performance in representing the spatial and interannual variability of leaf
      senescence, compared with the original phenology model in the Integrated
      Biosphere Simulator (IBIS). Our model explained approximately 63% of the EGS
      variations, whereas the original model explained much lower variations
      (coefficient of determination R2 = 0.01-0.18). In addition, the differences
      between the EGS reproduced by our model and the MODIS EGS at 71.3% of the pixels
      were within 10 days. For the original model, it is only 26.1%. We also found that
      the temperature threshold (TcritTm) of grassland was lower than that of woody
      species in the same latitudinal zone.

PMID- 27893827
TI  - Astrocyte Structural and Molecular Response to Elevated Intraocular Pressure
      Occurs Rapidly and Precedes Axonal Tubulin Rearrangement within the Optic Nerve
      Head in a Rat Model.
AB  - Glaucomatous axon injury occurs at the level of the optic nerve head (ONH) in
      response to uncontrolled intraocular pressure (IOP). The temporal response of ONH
      astrocytes (glial cells responsible for axonal support) to elevated IOP remains
      unknown. Here, we evaluate the response of actin-based astrocyte extensions and
      integrin-based signaling within the ONH to 8 hours of IOP elevation in a rat
      model. IOP elevation of 60 mm Hg was achieved under isoflurane anesthesia using
      anterior chamber cannulation connected to a saline reservoir. ONH astrocytic
      extension orientation was significantly and regionally rearranged immediately
      after IOP elevation (inferior ONH, 43.2 degrees  +/- 13.3 degrees  with respect
      to the anterior-posterior axis versus 84.1 degrees  +/- 1.3 degrees  in controls,
      p<0.05), and re-orientated back to baseline orientation 1 day post IOP
      normalization. ONH axonal microtubule filament label intensity was significantly
      reduced 1 and 3 days post IOP normalization, and returned to control levels on
      day 5. Phosphorylated focal adhesion kinase (FAK) levels steadily decreased after
      IOP normalization, while levels of phosphorylated paxillin (a downstream target
      of FAK involved in focal adhesion dynamics) were significantly elevated 5 days
      post IOP normalization. The levels of phosphorylated cortactin (a downstream
      target of Src kinase involved in actin polymerization) were significantly
      elevated 1 and 3 days post IOP normalization and returned to control levels by
      day 5. No significant axon degeneration was noted by morphologic assessment up to
      5 days post IOP normalization. Actin-based astrocyte structure and signaling
      within the ONH are significantly altered within hours after IOP elevation and
      prior to axonal cytoskeletal rearrangement, producing some responses that recover
      rapidly and others that persist for days despite IOP normalization.

PMID- 27893829
TI  - Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) Attenuates
      Type 2 Diabetes and Its Associated Cardiomyopathy.
AB  - BACKGROUND: Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae)
      rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal
      literature in India. Therefore, present experiments were carried out to explore
      the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR)
      against experimentally induced type 2 diabetes mellitus (T2DM) and its associated
      cardiomyopathy in Wistar rats. METHODS: SR was chemically characterized by GC-MS
      analysis. Antidiabetic activity of SR (50 and 100 mg/kg, orally) was measured in
      high fat diets (ad libitum) + low-single dose of streptozotocin (35 mg/kg,
      intraperitoneal) induced type 2 diabetic (T2D) rat. Fasting blood glucose level
      was measured at specific intermissions. Serum biochemical and inflammatory
      markers were estimated after sacrificing the animals. Besides, myocardial redox
      status, expressions of signal proteins (NF-kappaB and PKCs), histological and
      ultrastructural studies of heart were performed in the controls and SR treated
      T2D rats. RESULTS: Phytochemical screening of the crude extract revealed the
      presence of phenolic compounds, sugar alcohols, sterols, amino acids, saturated
      fatty acids within SR. T2D rats exhibited significantly (p < 0.01) higher fasting
      blood glucose level with respect to control. Alteration in serum lipid profile (p
      < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine
      kinase (p < 0.01) in the sera revealed the occurrence of hyperlipidemia and cell
      destruction in T2D rats. T2DM caused significant (p < 0.05-0.01) alteration in
      the biochemical markers in the sera. T2DM altered the redox status (p < 0.05
      0.01), decreased (p < 0.01) the intracellular NAD and ATP concentrations in the
      myocardial tissues of experimental rats. While investigating the molecular
      mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats
      also exhibited an up-regulation in nuclear NF-kappaB (p65) in the cardiac
      tissues. So, oral administration of SR (50 and 500 mg/kg) could reduce
      hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress,
      vascular inflammation and prevented the activation of oxidative stress induced
      signaling cascades leading to cell death. Histological and ultra-structural
      studies of cardiac tissues supported the protective characteristics of SR.
      CONCLUSIONS: From the present findings it can be concluded that, SR could offer
      protection against T2DM and its associated cardio-toxicity via multiple
      mechanisms viz. hypoglycemic, antioxidant and anti-inflammatory actions.

PMID- 27893832
TI  - Evolutionary Algorithm for RNA Secondary Structure Prediction Based on Simulated
      SHAPE Data.
AB  - BACKGROUND: Non-coding RNAs perform a wide range of functions inside the living
      cells that are related to their structures. Several algorithms have been proposed
      to predict RNA secondary structure based on minimum free energy. Low prediction
      accuracy of these algorithms indicates that free energy alone is not sufficient
      to predict the functional secondary structure. Recently, the obtained information
      from the SHAPE experiment greatly improves the accuracy of RNA secondary
      structure prediction by adding this information to the thermodynamic free energy
      as pseudo-free energy. METHOD: In this paper, a new method is proposed to predict
      RNA secondary structure based on both free energy and SHAPE pseudo-free energy.
      For each RNA sequence, a population of secondary structures is constructed and
      their SHAPE data are simulated. Then, an evolutionary algorithm is used to
      improve each structure based on both free and pseudo-free energies. Finally, a
      structure with minimum summation of free and pseudo-free energies is considered
      as the predicted RNA secondary structure. RESULTS AND CONCLUSIONS:
      Computationally simulating the SHAPE data for a given RNA sequence requires its
      secondary structure. Here, we overcome this limitation by employing a population
      of secondary structures. This helps us to simulate the SHAPE data for any RNA
      sequence and consequently improves the accuracy of RNA secondary structure
      prediction as it is confirmed by our experiments. The source code and web server
      of our proposed method are freely available at http://mostafa.ut.ac.ir/ESD-Fold/.

PMID- 27893830
TI  - Mechanistic Studies and Modeling Reveal the Origin of Differential Inhibition of
      Gag Polymorphic Viruses by HIV-1 Maturation Inhibitors.
AB  - HIV-1 maturation inhibitors (MIs) disrupt the final step in the HIV-1 protease
      mediated cleavage of the Gag polyprotein between capsid p24 capsid (CA) and
      spacer peptide 1 (SP1), leading to the production of infectious virus. BMS-955176
      is a second generation MI with improved antiviral activity toward polymorphic Gag
      variants compared to a first generation MI bevirimat (BVM). The underlying
      mechanistic reasons for the differences in polymorphic coverage were studied
      using antiviral assays, an LC/MS assay that quantitatively characterizes CA/SP1
      cleavage kinetics of virus like particles (VLPs) and a radiolabel binding assay
      to determine VLP/MI affinities and dissociation kinetics. Antiviral assay data
      indicates that BVM does not achieve 100% inhibition of certain polymorphs, even
      at saturating concentrations. This results in the breakthrough of infectious
      virus (partial antagonism) regardless of BVM concentration. Reduced maximal
      percent inhibition (MPI) values for BVM correlated with elevated EC50 values,
      while rates of HIV-1 protease cleavage at CA/SP1 correlated inversely with the
      ability of BVM to inhibit HIV-1 Gag polymorphic viruses: genotypes with more
      rapid CA/SP1 cleavage kinetics were less sensitive to BVM. In vitro inhibition of
      wild type VLP CA/SP1 cleavage by BVM was not maintained at longer cleavage times.
      BMS-955176 exhibited greatly improved MPI against polymorphic Gag viruses, binds
      to Gag polymorphs with higher affinity/longer dissociation half-lives and
      exhibits greater time-independent inhibition of CA/SP1 cleavage compared to BVM.
      Virological (MPI) and biochemical (CA/SP1 cleavage rates, MI-specific Gag
      affinities) data were used to create an integrated semi-quantitative model that
      quantifies CA/SP1 cleavage rates as a function of both MI and Gag polymorph. The
      model outputs are in accord with in vitro antiviral observations and correlate
      with observed in vivo MI efficacies. Overall, these findings may be useful to
      further understand antiviral profiles and clinical responses of MIs at a basic
      level, potentially facilitating further improvements to MI potency and coverage.

PMID- 27893831
TI  - Retinal Pre-Conditioning by CD59a Knockout Protects against Light-Induced
      Photoreceptor Degeneration.
AB  - Complement dysregulation plays a key role in the pathogenesis of age-related
      macular degeneration (AMD), but the specific mechanisms are incompletely
      understood. Complement also potentiates retinal degeneration in the murine light
      damage model. To test the retinal function of CD59a, a complement inhibitor,
      CD59a knockout (KO) mice were used for light damage (LD) experiments. Retinal
      degeneration and function were compared in WT versus KO mice following light
      damage. Gene expression changes, endoplasmic reticulum (ER) stress, and glial
      cell activation were also compared. At baseline, the ERG responses and rhodopsin
      levels were lower in CD59aKO compared to wild-type (WT) mice. Following LD, the
      ERG responses were better preserved in CD59aKO compared to WT mice.
      Correspondingly, the number of photoreceptors was higher in CD59aKO retinas than
      WT controls after LD. Under normal light conditions, CD59aKO mice had higher
      levels than WT for GFAP immunostaining in Muller cells, mRNA and protein levels
      of two ER-stress markers, and neurotrophic factors. The reduction in photon
      capture, together with the neurotrophic factor upregulation, may explain the
      structural and functional protection against LD in the CD59aKO.

PMID- 27893833
TI  - Increasing the Size of the Microbial Biomass Altered Bacterial Community
      Structure which Enhances Plant Phosphorus Uptake.
AB  - Agricultural production can be limited by low phosphorus (P) availability, with
      soil P being constrained by sorption and precipitation reactions making it less
      available for plant uptake. There are strong links between carbon (C) and
      nitrogen (N) availability and P cycling within soil P pools, with microorganisms
      being an integral component of soil P cycling mediating the availability of P to
      plants. Here we tested a conceptual model that proposes (i) the addition of
      readily-available organic substrates would increase the size of the microbial
      biomass thus exhausting the pool of easily-available P and (ii) this would cause
      the microbial biomass to access P from more recalcitrant pools. In this model it
      is hypothesised that the size of the microbial population is regulating access to
      less available P rather than the diversity of organisms contained within this
      biomass. To test this hypothesis we added mixtures of simple organic compounds
      that reflect typical root exudates at different C:N ratios to a soil microcosm
      experiment and assessed changes in soil P pools, microbial biomass and bacterial
      diversity measures. We report that low C:N ratio (C:N = 12.5:1) artificial root
      exudates increased the size of the microbial biomass while high C:N ratio (C:N =
      50:1) artificial root exudates did not result in a similar increase in microbial
      biomass. Interestingly, addition of the root exudates did not alter bacterial
      diversity (measured via univariate diversity indices) but did alter bacterial
      community structure. Where C, N and P supply was sufficient to support plant
      growth the increase observed in microbial biomass occurred with a concurrent
      increase in plant yield.

PMID- 27893834
TI  - Selective Pressure Promotes Tetracycline Resistance of Chlamydia Suis in
      Fattening Pigs.
AB  - In pigs, Chlamydia suis has been associated with respiratory disease, diarrhea
      and conjunctivitis, but there is a high rate of inapparent C. suis infection
      found in the gastrointestinal tract of pigs. Tetracycline resistance in C. suis
      has been described in the USA, Italy, Switzerland, Belgium, Cyprus and Israel.
      Tetracyclines are commonly used in pig production due to their broad-spectrum
      activity and relatively low cost. The aim of this study was to isolate clinical
      C. suis samples in cell culture and to evaluate their antibiotic susceptibility
      in vitro under consideration of antibiotic treatment on herd level. Swab samples
      (n = 158) identified as C. suis originating from 24 farms were further processed
      for isolation, which was successful in 71% of attempts with a significantly
      higher success rate from fecal swabs compared to conjunctival swabs. The farms
      were divided into three treatment groups: A) farms without antibiotic treatment,
      B) farms with prophylactic oral antibiotic treatment of the whole herd consisting
      of trimethoprime, sulfadimidin and sulfathiazole (TSS), or C) farms giving herd
      treatment with chlortetracycline with or without tylosin and sulfadimidin (CTS).
      59 isolates and their corresponding clinical samples were selected and tested for
      the presence or absence of the tetracycline resistance class C gene [tet(C)] by
      conventional PCR and isolates were further investigated for their antibiotic
      susceptibility in vitro. The phenotype of the investigated isolates was either
      classified as tetracycline sensitive (Minimum inhibitory concentration [MIC] < 2
      MUg/ml), intermediate (2 MUg/ml <= MIC < 4 MUg/ml) or resistant (MIC >= 4
      MUg/ml). Results of groups and individual pigs were correlated with antibiotic
      treatment and time of sampling (beginning/end of the fattening period). We found
      clear evidence for selective pressure as absence of antibiotics led to isolation
      of only tetracycline sensitive or intermediate strains whereas tetracycline
      treatment resulted in a greater number of tetracycline resistant isolates.

PMID- 27893835
TI  - Onset of Oviposition Triggers Abrupt Reduction in Migratory Flight Behavior and
      Flight Muscle in the Female Beet Webworm, Loxostege sticticalis.
AB  - Flight and reproduction are usually considered as two life history traits that
      compete for resources in a migratory insect. The beet webworm, Loxostege
      sticticalis L., manages the costs of migratory flight and reproduction through a
      trade-off in timing of these two life history traits, where migratory behavior
      occurs during the preoviposition period. To gain insight into how migratory
      flight and reproduction are coordinated in the female beet webworm, we conducted
      experiments beginning at the end of the preoviposition period. We used flight
      mills to test whether flight performance and supportive flight musculature and
      fuel are affected by the number of eggs oviposited, or by the age of mated and
      unmated females after onset of oviposition by the former. The results showed that
      flight distance, flight velocity, flight duration, and flight muscle mass
      decreased abruptly at the onset of oviposition, compared to that of virgin
      females of the same age which did not change over the next 7 d. These results
      indicate that onset of oviposition triggers a decrease in flight performance and
      capacity in female beet webworms, as a way of actively managing reallocation of
      resources away from migratory flight and into egg production. In addition to the
      abrupt switch, there was a gradual, linear decline in flight performance, flight
      muscle mass, and flight fuel relative to the number of eggs oviposited. The
      histolysis of flight muscle and decrease of triglyceride content indicate a
      progressive degradation in the ability of adults to perform additional migratory
      flights after onset of oviposition. Although the results show that substantial,
      albeit reduced, long-duration flights remain possible after oviposition begins,
      additional long-distance migratory flights probably are not launched after the
      initiation of oviposition.

PMID- 27893836
TI  - Prognostic Value of Serum Free Light Chains Measurements in Multiple Myeloma
      Patients.
AB  - BACKGROUND: The outcome for patients with Multiple Myeloma (MM) is highly
      variable, therefore, the existence of robust and easy to determine prognostic
      markers is extremely important for an efficient management of these patients.
      Presently, there is a debate about the role of the serum free light chains (sFLC)
      in the prognosis of MM patients both at diagnosis and after treatment. The aim of
      this study is to evaluate in a cohort of newly diagnosed MM patients from the
      Southern area of Spain, the prognostic value of sFLC both at baseline and after
      treatment. MATERIALS AND METHODS: 180 patients with a median age of 69 years were
      followed-up for a median time of 35 (18-61) months. The sFLC ratio (sFLCR) was
      calculated using the monoclonal sFLC as numerator. Patients were divided in two
      groups according to a sFLCR cut-off based on ROC analysis. The primary endpoints
      were the Overall Survival (OS) and the Progression-free Survival (PFS).
      Additionally, thirty-six MM patients treated with novel agents
      (Bortezomib/Dexamethasone) that achieved Complete Response (CR) or stringent CR
      (sCR) before autologous stem cell transplantation were studied to assess the
      impact of sCR in Disease Free Survival (DFS) and OS. RESULTS: During follow-up
      there were 72 disease-related deaths. The 5-years OS for the whole group was 51%.
      However, separate analysis of patients with sFLCR above (group "high") or below
      (groups "low") the cut-off value of 47 shows an OS of 23% and 73%, respectively
      (HR = 5.03, 95%CI 2.99-8.50, p<0.001). In addition, analysis by ISS stage, showed
      that the presence of high sFLCR was always significantly associated with a worse
      OS. Multivariate analysis identified sFLCR (HR = 4.42, 95%CI 2.57-7.60, p<0.001)
      and beta-2-microglobulin (B2M) (HR = 3.04, 95%IC 1.75-5.31, p<0.001) as
      independent risk factors for adverse outcome. A new risk stratification model
      based on sFLCR>=47 and B2M>3.5 mg/L provided a statistically more significant
      result for this cohort when compared with the conventional ISS system. The HR for
      the new model were 2.84 (95% CI, 1.39-5.79, p = 0.004) for patients in stage 2
      and 15.39 (95% CI, 6.35-37.33, p<0.001) for those in stage 3. Finally, in the
      group of patients reaching CR (19/36) or sCR (17/36) after induction, the median
      DFS for CR patients was 29 months, and NR for sCR patients (HR = 3.73; 95% CI
      1.15-12.13, p = 0.03). Importantly, achieving sCR also translated into a
      significantly longer OS (5y-OS: sCR-89% versus CR-49%; p = 0.003; OS: sCR-NR
      versus CR-52 months). CONCLUSIONS: Our findings confirm the observations that the
      sFLCR has a major role in the survival of MM patients. A cut-off of sFLCR>=47 was
      shown to have an independent prognostic value at diagnosis, and a proposed "New
      Staging System" allows an accurate and simple method to risk stratify MM
      patients. Furthermore, because achievement of sCR was shown to represent a
      response state deeper than conventional CR resulting in greater OS and DFS, our
      study supports the continuity of sFLC ratio as part of the response criteria for
      MM patients.

PMID- 27893838
TI  - Performance Evaluation of Malaria Microscopists at Defense Health Facilities in
      Addis Ababa and Its Surrounding Areas, Ethiopia.
AB  - BACKGROUND: Blood film microscopy is the gold standard approach for malaria
      diagnosis, and preferred method for routine patient diagnosis in health
      facilities. However, the inability of laboratory professionals to correctly
      detect and identify malaria parasites microscopically leads to an inappropriate
      administration of anti-malarial drugs to the patients and incorrect findings in
      research areas. This study was carried out to evaluate the performance of
      laboratory professionals in malaria diagnosis in health facilities under the
      Defense Health Main Department in Addis Ababa and its surroundings, Ethiopia.
      METHOD: A cross sectional study was conducted from June to July 2015. Totally, 60
      laboratory professionals out of the selected 16 health facilities were included
      in the study. Data were collected by distributing standardized pre-validated
      malaria slide-panels and self-administered questionnaires among professionals,
      onsite in each study facility. Sensitivity, specificity, and strength of
      agreement (with kappa score) in performance among the study participants against
      WHO-certified expert malaria microscopists were calculated. RESULT: Of the 60
      study participants, 8.3% (5/60) correctly read all the distributed slides in
      terms of parasite detection, species identification and parasite counting;
      whereas, each of the remaining 55(91.7%) interpreted at least two slides
      incorrectly. The overall sensitivity and specificity of participants' performance
      in detection of malaria parasites were 65.7% and 100%, respectively. Overall,
      fair agreement (71.4%; Kappa: 0.4) in detection of malaria parasite was observed
      between the study subjects and expert readers. The overall sensitivity and
      specificity of participants in species identification of malaria parasites were
      respectively 41.3% and 100%. Overall, slight agreement (51.1%; kappa: 0.04) in
      identification of malaria species was observed. Generally, agreement was lower in
      parasite detection and species identification at low parasite density and mixed
      infection cases. CONCLUSION: The general agreement between the study participants
      and expert microscopists in malaria parasite detection and species identification
      was very low, particularly in the cases of low-parasite density and mixed
      infections. Therefore, regular external quality assessments and further
      refreshment trainings are crucial to enhance the skill of professionals in
      malaria microscopy; particularly for those in non-malarious areas where exposure
      to malaria diagnosis is low.

PMID- 27893837
TI  - Cell Type-Specific Modulation of Cobalamin Uptake by Bovine Serum.
AB  - Tracking cellular 57Co-labelled cobalamin (57Co-Cbl) uptake is a well-established
      method for studying Cbl homeostasis. Previous studies established that bovine
      serum is not generally permissive for cellular Cbl uptake when used as a
      supplement in cell culture medium, whereas supplementation with human serum
      promotes cellular Cbl uptake. The underlying reasons for these differences are
      not fully defined. In the current study we address this question. We extend
      earlier observations by showing that fetal calf serum inhibits cellular 57Co-Cbl
      uptake by HT1080 cells (a fibrosarcoma-derived fibroblast cell line).
      Furthermore, we discovered that a simple heat-treatment protocol (95 degrees C
      for 10 min) ameliorates this inhibitory activity for HT1080 cell 57Co-Cbl uptake.
      We provide evidence that the very high level of haptocorrin in bovine serum (as
      compared to human serum) is responsible for this inhibitory activity. We suggest
      that bovine haptocorrin competes with cell-derived transcobalamin for Cbl
      binding, and that cellular Cbl uptake may be minimised in the presence of large
      amounts of bovine haptocorrin that are present under routine in vitro cell
      culture conditions. In experiments conducted with AG01518 cells (a neonatal
      foreskin-derived fibroblast cell line), overall cellular 57Co-Cbl uptake was 86%
      lower than for HT1080 cells, cellular TC production was below levels detectable
      by western blotting, and heat treatment of fetal calf serum resulted in only a
      modest increase in cellular 57Co-Cbl uptake. We recommend a careful assessment of
      cell culture protocols should be conducted in order to determine the potential
      benefits that heat-treated bovine serum may provide for in vitro studies of
      mammalian cell lines.

PMID- 27893839
TI  - No Association between TNF-alpha -308G/A Polymorphism and Idiopathic Recurrent
      Miscarriage: A Systematic Review with Meta-Analysis and Trial Sequential
      Analysis.
AB  - BACKGROUND: Conflicting results were reported on the association between the TNF
      alpha -308G/A polymorphism and idiopathic recurrent miscarriage (IRM). Though
      three meta-analyses have been conducted on this topic, the conclusions were
      contradictory, and the results may be unreliable as certain crucial conditions
      were neglected. METHOD: A complete search was conducted in PubMed, Cochrane
      Library, and Embase, other sources like Google Scholar, ClinicalTrial.gov and
      reference lists of relevant articles were also retrieved. All candidate articles
      were accessed and screened using specific inclusion and exclusion criteria.
      Statistical analyses were performed on data extracted from eligible studies using
      the STATA 12.0 software and the TSA 0.9 beta software. RESULTS: Eventually, 12
      case-control studies from 11 publications (with 1,807 cases and 2,012 controls)
      were included in this meta-analysis, and no evidence of any significant
      association was found in the overall analyses between the TNF-alpha -308G/A
      polymorphism and IRM risk. However, significant association was shown in Asian
      population (four studies from three publications) in the dominant model (AA + GA
      vs. GG), the allelic model (A vs. G), and the heterozygote model (GA vs. GG).
      CONCLUSIONS: TNF-alpha -308G/A polymorphism is not associated with IRM risk.
      Though significant association was found in Asian population, the result needs
      further confirmation from more studies.

PMID- 27893840
TI  - Impact of Prolonged Temporal Discrimination Threshold on Finger Movements of
      Parkinson's Disease.
AB  - INTRODUCTION: Sensory information is essential for the precise control of
      movement. Patients with Parkinson's disease (PD) have higher-order sensory
      dysfunctions including prolonged temporal discrimination threshold (TDT).
      However, the impact of prolonged TDT on parkinsonian motor deficits is uncertain.
      METHODS: This study includes 33 PD patients and 24 healthy controls. TDT values
      were measured in the index finger. Using coin rotation task (CRT), dexterous
      finger movement was assessed. Using an inertial sensor, the speed, amplitude, and
      frequency of finger tapping were measured. The impact of prolonged index finger
      TDT on two different finger movements was analyzed using the general estimating
      equation. RESULTS: Compared to healthy controls, TDT was prolonged in the PD
      patients. There was no impact of TDT on mean values or decrement for amplitude
      and speed, as well as mean values, decrement and variability of tapping
      frequency. However, prolonged TDT had a significant impact on the variability in
      amplitude (B = 436.905 * 10-4, Wald chi2 = 9.140, p = 0.014) and speed (B =
      425.655 * 10-4, Wald chi2 = 9.876, p = 0.014) of finger tapping. There was a
      marginal correlation between TDT and CRT. In addition, CRT correlated with
      variability in amplitude and speed of finger tapping. CONCLUSION: In PD,
      cutaneous temporal discriminative sensory dysfunction appears to be related to
      increased variabilities in the speed and amplitude of fast repetitive finger
      movements and disturbed finger dexterity.

PMID- 27893841
TI  - Seroprevalence of Cutaneous Human Papillomaviruses and the Risk of External
      Genital Lesions in Men: A Nested Case-Control Study.
AB  - BACKGROUND: A variety of cutaneous human papillomaviruses (HPV) are detectable in
      genital epithelial lesions in men and non-melanoma skin cancer patients. It
      remains unclear whether these viruses are associated causally with skin lesions.
      To date, no study has prospectively examined the association between cutaneous
      HPV seropositivity and development of external genital lesions (EGLs) in men.
      OBJECTIVES: To examine the association between seropositivity to cutaneous HPV
      types and the risk of subsequent development of EGLs. METHODS: A nested case
      control study including 163 incident EGL cases and 352 EGL-free controls in the
      HPV Infection in Men (HIM) Study cohort was conducted. Cases were ascertained at
      each of up to 10 biannual clinical visits and verified through biopsy and
      pathological diagnoses. EGLs were categorized as condyloma, suggestive of
      condyloma, penile intraepithelial neoplasia (PeIN), and other EGLs. Archived
      serum specimens collected at baseline were tested for antibodies against 14
      cutaneous HPV types (beta types (5, 8, 12, 14, 17, 22, 23, 24, 38, and 47), alpha
      type 27, gamma type 4, MU type 1, and nu type 41) using a GST L1-based multiplex
      serology assay. Socio-demographic and sexual behavior data were collected through
      a questionnaire. Using logistic regression, adjusted odds ratios (AOR) and 95%
      confidence intervals (CI) were estimated. RESULTS: Overall, seropositivity to >=1
      cutaneous HPV type (any-HPV) and >=1 beta types (any-beta) was 58.3% and 37.5%
      among other EGL cases, 71.6% and 46.8% among condyloma, 66.8% and 50.0% among
      PeIN, and 71.9% and 38.4% among controls, respectively. Type-specific
      seropositivity was most common for ?-HPV 4, MU-HPV 1, and beta-HPV 8. No
      statistically significant association was observed between any-HPV, any-beta, and
      type-specific HPV seropositivity and subsequent development of EGLs across all
      pathological diagnoses. CONCLUSIONS: Overall, seropositivity to cutaneous HPV was
      common among men; however, it appears that cutaneous HPV is not associated with
      the development of genital lesions in men.

PMID- 27893842
TI  - T Cell Receptor Vbeta Staining Identifies the Malignant Clone in Adult T cell
      Leukemia and Reveals Killing of Leukemia Cells by Autologous CD8+ T cells.
AB  - There is growing evidence that CD8+ cytotoxic T lymphocyte (CTL) responses can
      contribute to long-term remission of many malignancies. The etiological agent of
      adult T-cell leukemia/lymphoma (ATL), human T lymphotropic virus type-1 (HTLV-1),
      contains highly immunogenic CTL epitopes, but ATL patients typically have low
      frequencies of cytokine-producing HTLV-1-specific CD8+ cells in the circulation.
      It remains unclear whether patients with ATL possess CTLs that can kill the
      malignant HTLV-1 infected clone. Here we used flow cytometric staining of
      TCRVbeta and cell adhesion molecule-1 (CADM1) to identify monoclonal populations
      of HTLV-1-infected T cells in the peripheral blood of patients with ATL. Thus, we
      quantified the rate of CD8+-mediated killing of the putative malignant clone in
      ex vivo blood samples. We observed that CD8+ cells from ATL patients were unable
      to lyse autologous ATL clones when tested directly ex vivo. However, short in
      vitro culture restored the ability of CD8+ cells to kill ex vivo ATL clones in
      some donors. The capacity of CD8+ cells to lyse HTLV-1 infected cells which
      expressed the viral sense strand gene products was significantly enhanced after
      in vitro culture, and donors with an ATL clone that expressed the HTLV-1 Tax gene
      were most likely to make a detectable lytic CD8+ response to the ATL cells. We
      conclude that some patients with ATL possess functional tumour-specific CTLs
      which could be exploited to contribute to control of the disease.

PMID- 27893843
TI  - Comparative Effectiveness of Smoking Cessation Medications: A National
      Prospective Cohort From Taiwan.
AB  - BACKGROUND AND OBJECTIVE: Relative effectiveness of smoking cessation medications
      varenicline, bupropion and nicotine replacement therapy (NRT)-remains unclear
      among smokers in real-world settings. Evidence in females and smokers with
      light/moderate nicotine dependence is particularly insufficient. This study
      compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT
      patch, in achieving abstinence among recent quitters. METHODS: In a national
      smoking cessation program in Taiwan (2012-2015), a cohort of 11,968 participants
      received varenicline (n = 5,052), bupropion (n = 823), NRT gum (n = 1944) or NRT
      patch (n = 4,149). The 7-day, 1-month or 6-month point-prevalence was calculated
      based on self-reported last smoking event via telephone interview after 6 months.
      Logistic regression modellings estimated odds ratios (OR) and 95% confidence
      intervals (CI) for achieving abstinence using different modalities (NRT patch as
      referent). Models included age, sex, education, marital status, geographic
      region, smoke-years, nicotine-dependence level, medical institution, number of
      clinic visits and medication use duration. Analyses were further stratified by
      sex and dependence severity. RESULTS: Participants were predominantly male (83%)
      with a mean age of 43.7+/-12.6 years. Varenicline users were more likely than NRT
      patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30,
      CI: 1.19-1.44), 1-month point-prevalence (OR = 1.36, CI: 1.24-1.50) or 6-month
      point-prevalence (OR = 1.30, CI: 1.14-1.47). Compared with NRT patch, varenicline
      was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01
      1.65), men (OR = 1.31, CI: 1.18-1.46), those with light/moderate dependence (OR =
      1.42, CI: 1.24-1.63) or smokers with severe dependence (OR = 1.19, CI: 1.04
      1.37), based on 7-day point-prevalence. Differences in effectiveness were not
      observed between users of bupropion, NRT gum and NRT patch. CONCLUSIONS: In
      smoking cessation clinics in Taiwan, varenicline users reported higher abstinence
      rates than NRT patch users after 6 months. Women and smokers with light/moderate
      nicotine dependence may also benefit from varenicline in actual clinical
      practice.

PMID- 27893844
TI  - The Florida Harvester Ant, Pogonomyrmex badius, Relies on Germination to Consume
      Large Seeds.
AB  - The Florida harvester ant, Pogonomyrmex badius, is one of many ant species and
      genera that stores large numbers of seeds in damp, underground chambers for later
      consumption. A comparison of the sizes of seeds recovered from storage chambers
      with those of seed husks discarded following consumption revealed that the used
      seeds are far smaller than stored seeds. This difference in use-rate was
      confirmed in field and laboratory colonies by offering marked seeds of various
      sizes and monitoring the appearance of size-specific chaff. Because foragers
      collect a range of seed sizes but only open small seeds, large seeds accumulate,
      forming 70% or more of the weight of seed stores. Major workers increase the
      rates at which small and medium seeds are opened, but do not increase the size
      range of opened seeds. Experiments limiting ant access to portions of natural
      seed chambers showed that seeds germinate during storage, but that the ants
      rapidly remove them. When offered alongside non germinating seeds, germinating
      seeds were preferentially fed to larvae. The rate of germination during the
      annual cycle was determined by both burial in artificial chambers at various
      depths and under four laboratory temperatures. The germination rate depends upon
      the species of seed, the soil/laboratory temperature and/or the elapsed time. The
      seasonal soil temperature cycle generated germination patterns that vary with the
      mix of locally-available seeds. Taken together, exploitation of germination
      greatly increases the resources available to the ants in space and time. While
      the largest seeds may have the nutritional value of 15 small seeds, the inability
      of workers to open large seeds at will precludes them from rapid use during
      catastrophic events. The harvester ant's approach to seed harvesting is therefore
      two-pronged, with both immediate and delayed payoffs arising from the tendency to
      forage for a wide variety of seeds sizes.

PMID- 27893845
TI  - Meta-Heuristics in Short Scale Construction: Ant Colony Optimization and Genetic
      Algorithm.
AB  - The advent of large-scale assessment, but also the more frequent use of
      longitudinal and multivariate approaches to measurement in psychological,
      educational, and sociological research, caused an increased demand for
      psychometrically sound short scales. Shortening scales economizes on valuable
      administration time, but might result in inadequate measures because reducing an
      item set could: a) change the internal structure of the measure, b) result in
      poorer reliability and measurement precision, c) deliver measures that cannot
      effectively discriminate between persons on the intended ability spectrum, and d)
      reduce test-criterion relations. Different approaches to abbreviate measures fare
      differently with respect to the above-mentioned problems. Therefore, we compare
      the quality and efficiency of three item selection strategies to derive short
      scales from an existing long version: a Stepwise COnfirmatory Factor Analytical
      approach (SCOFA) that maximizes factor loadings and two metaheuristics,
      specifically an Ant Colony Optimization (ACO) with a tailored user-defined
      optimization function and a Genetic Algorithm (GA) with an unspecific cost
      reduction function. SCOFA compiled short versions were highly reliable, but had
      poor validity. In contrast, both metaheuristics outperformed SCOFA and produced
      efficient and psychometrically sound short versions (unidimensional, reliable,
      sensitive, and valid). We discuss under which circumstances ACO and GA produce
      equivalent results and provide recommendations for conditions in which it is
      advisable to use a metaheuristic with an unspecific out-of-the-box optimization
      function.

PMID- 27893847
TI  - A2A Adenosine Receptor Antagonism Reverts the Blood-Brain Barrier Dysfunction
      Induced by Sleep Restriction.
AB  - Chronic sleep restriction induces blood-brain barrier disruption and increases
      pro-inflammatory mediators in rodents. Those inflammatory mediators may modulate
      the blood-brain barrier and constitute a link between sleep loss and blood-brain
      barrier physiology. We propose that adenosine action on its A2A receptor may be
      modulating the blood-brain barrier dynamics in sleep-restricted rats. We
      administrated a selective A2A adenosine receptor antagonist (SCH58261) in sleep
      restricted rats at the 10th day of sleep restriction and evaluated the blood
      brain barrier permeability to dextrans coupled to fluorescein (FITC-dextrans) and
      Evans blue. In addition, we evaluated by western blot the expression of tight
      junction proteins (claudin-5, occludin, ZO-1), adherens junction protein (E
      cadherin), A2A adenosine receptor, adenosine-synthesizing enzyme (CD73), and
      neuroinflammatory markers (Iba-1 and GFAP) in the cerebral cortex, hippocampus,
      basal nuclei and cerebellar vermis. Sleep restriction increased blood-brain
      barrier permeability to FITC-dextrans and Evans blue, and the effect was reverted
      by the administration of SCH58261 in almost all brain regions, excluding the
      cerebellum. Sleep restriction increased the expression of A2A adenosine receptor
      only in the hippocampus and basal nuclei without changing the expression of CD73
      in all brain regions. Sleep restriction reduced the expression of tight junction
      proteins in all brain regions, except in the cerebellum; and SCH58261 restored
      the levels of tight junction proteins in the cortex, hippocampus and basal
      nuclei. Finally, sleep restriction induced GFAP and Iba-1 overexpression that was
      attenuated with the administration of SCH58261. These data suggest that the
      action of adenosine on its A2A receptor may have a crucial role in blood-brain
      barrier dysfunction during sleep loss probably by direct modulation of brain
      endothelial cell permeability or through a mechanism that involves gliosis with
      subsequent inflammation and increased blood-brain barrier permeability.

PMID- 27893846
TI  - Cerebellum Transcriptome of Mice Bred for High Voluntary Activity Offers Insights
      into Locomotor Control and Reward-Dependent Behaviors.
AB  - The role of the cerebellum in motivation and addictive behaviors is less
      understood than that in control and coordination of movements. High running can
      be a self-rewarding behavior exhibiting addictive properties. Changes in the
      cerebellum transcriptional networks of mice from a line selectively bred for High
      voluntary running (H) were profiled relative to an unselected Control (C) line.
      The environmental modulation of these changes was assessed both in activity
      environments corresponding to 7 days of Free (F) access to running wheel and to
      Blocked (B) access on day 7. Overall, 457 genes exhibited a significant (FDR
      adjusted P-value < 0.05) genotype-by-environment interaction effect, indicating
      that activity genotype differences in gene expression depend on environmental
      access to running. Among these genes, network analysis highlighted 6 genes (Nrgn,
      Drd2, Rxrg, Gda, Adora2a, and Rab40b) connected by their products that displayed
      opposite expression patterns in the activity genotype contrast within the B and F
      environments. The comparison of network expression topologies suggests that
      selection for high voluntary running is linked to a predominant dysregulation of
      hub genes in the F environment that enables running whereas a dysregulation of
      ancillary genes is favored in the B environment that blocks running. Genes
      associated with locomotor regulation, signaling pathways, reward-processing, goal
      focused, and reward-dependent behaviors exhibited significant genotype-by
      environment interaction (e.g. Pak6, Adora2a, Drd2, and Arhgap8). Neuropeptide
      genes including Adcyap1, Cck, Sst, Vgf, Npy, Nts, Penk, and Tac2 and related
      receptor genes also exhibited significant genotype-by-environment interaction.
      The majority of the 183 differentially expressed genes between activity genotypes
      (e.g. Drd1) were under-expressed in C relative to H genotypes and were also under
      expressed in B relative to F environments. Our findings indicate that the high
      voluntary running mouse line studied is a helpful model for understanding the
      molecular mechanisms in the cerebellum that influence locomotor control and
      reward-dependent behaviors.

PMID- 27893848
TI  - The Open Form Inducer Approach for Structure-Based Drug Design.
AB  - Many open form (OF) structures of drug targets were obtained a posteriori by
      analysis of co-crystals with inhibitors. Therefore, obtaining the OF structure of
      a drug target a priori will accelerate development of potent inhibitors. In
      addition to its small active site, Trypanosoma cruzi dihydroorotate dehydrogenase
      (TcDHODH) is fully functional in its monomeric form, making drug design
      approaches targeting the active site and protein-protein interactions
      unrealistic. Therefore, a novel a priori approach was developed to determination
      the TcDHODH active site in OF. This approach consists of generating an "OF
      inducer" (predicted in silico) to bind the target and cause steric repulsion with
      flexible regions proximal to the active site that force it open. We provide the
      first proof-of-concept of this approach by predicting and crystallizing TcDHODH
      in complex with an OF inducer, thereby obtaining the OF a priori with its
      subsequent use in designing potent and selective inhibitors. Fourteen co-crystal
      structures of TcDHODH with the designed inhibitors are presented herein. This
      approach has potential to encourage drug design against diseases where the
      molecular targets are such difficult proteins possessing small AS volume. This
      approach can be extended to study open/close conformation of proteins in general,
      the identification of allosteric pockets and inhibitors for other drug targets
      where conventional drug design approaches are not applicable, as well as the
      effective exploitation of the increasing number of protein structures deposited
      in Protein Data Bank.

PMID- 27893849
TI  - Features of Age-Related Macular Degeneration in the General Adults and Their
      Dependency on Age, Sex, and Smoking: Results from the German KORA Study.
AB  - Age-related macular degeneration (AMD) is a vision impairing disease of the
      central retina characterized by early and late forms in individuals older than 50
      years of age. However, there is little knowledge to what extent also younger
      adults are affected. We have thus set out to estimate the prevalence of early AMD
      features and late AMD in a general adult population by acquiring color fundus
      images in 2,840 individuals aged 25 to 74 years of the Cooperative Health
      Research in the Region of Augsburg project (KORA) in South Germany. Among the
      2,546 participants with gradable images for each eye, 10.9% (n = 277) had early
      AMD features (applying the 9-step Age-Related Eye Disease Study Severity Scale),
      0.2% (n = 6) had late AMD. Prevalence increased with age, reaching 26.3% for
      early AMD features and 1.9% for late AMD at the age 70+. However, signs of early
      AMD were found in subjects as young as 25 years, with the risk for early AMD
      features increasing linearly by years of age in men, and, less consistent with a
      linear increase, in women. Risk for early AMD features increased linearly by pack
      years of smoking in men, not in women, nor was there any association with other
      lifestyle or metabolic factors. By providing much sought-after prevalence
      estimates for AMD from Central Europe, our data underscores a substantial
      proportion of the adult population with signs of early AMD, including individuals
      younger than 50 years. This supports the notion that early AMD features in the
      young might be under-acknowledged.

PMID- 27893850
TI  - A Convenient In Vivo Model Using Small Interfering RNA Silencing to Rapidly
      Assess Skeletal Gene Function.
AB  - It is difficult to study bone in vitro because it contains various cell types
      that engage in cross-talk. Bone biologically links various organs, and it has
      thus become increasingly evident that skeletal physiology must be studied in an
      integrative manner in an intact animal. We developed a model using local
      intraosseous small interfering RNA (siRNA) injection to rapidly assess the
      effects of a target gene on the local skeletal environment. In this model, 160-g
      male Sprague-Dawley rats were treated for 1-2 weeks. The left tibia received
      intraosseous injection of a parathyroid hormone 1 receptor (Pth1r) or insulin
      like growth factor 1 receptor (Igf-1r) siRNA transfection complex loaded in
      poloxamer 407 hydrogel, and the right tibia received the same volume of control
      siRNA. All the tibias received an intraosseous injection of recombinant human
      parathyroid hormone (1-34) (rhPTH (1-34)) or insulin-like growth factor-1 (IGF
      1). Calcein green and alizarin red were injected 6 and 2 days before euthanasia,
      respectively. IGF-1R and PTH1R expression levels were detected via RT-PCR assays
      and immunohistochemistry. Bone mineral density (BMD), microstructure, mineral
      apposition rates (MARs), and strength were determined by dual-energy X-ray
      absorptiometry, micro-CT, histology and biomechanical tests. The RT-PCR and
      immunohistochemistry results revealed that IGF-1R and PTH1R expression levels
      were dramatically diminished in the siRNA-treated left tibias compared to the
      right tibias (both p<0.05). Using poloxamer 407 hydrogel as a controlled-release
      system prolonged the silencing effect of a single dose of siRNA; the mRNA
      expression levels of IGF-1R were lower at two weeks than at one week (p<0.01).
      The BMD, bone microstructure parameters, MAR and bone strength were significantly
      decreased in the left tibias compared to the right tibias (all p<0.05). This
      simple and convenient local intraosseous siRNA injection model achieved gene
      silencing with very small quantities of siRNA over a short treatment period (<=7
      days).

PMID- 27893851
TI  - Expression and Regulation of PIWIL-Proteins and PIWI-Interacting RNAs in
      Rheumatoid Arthritis.
AB  - OBJECTIVE: The PIWIL (P-element induced wimpy testis like protein) subfamily of
      argonaute proteins is essential for Piwi-interacting RNA (piRNA) biogenesis and
      their function to silence transposons during germ-line development. Here we
      explored their presence and regulation in rheumatoid arthritis (RA). METHODS: The
      expression of PIWIL genes in RA and osteoarthritis (OA) synovial tissues and
      synovial fibroblasts (SF) was analysed by Real-time PCR, immunofluorescence and
      Western blot. The expression of piRNAs was quantified by next generation small
      RNA sequencing (NGS). The regulation of PIWI/piRNAs, proliferation and
      methylation of LINE-1 after silencing of PIWIL genes were studied. RESULTS:
      PIWIL2 and 4 mRNA were similarly expressed in synovial tissues and SF from RA and
      OA patients. However, on the protein level only PIWIL4 was strongly expressed in
      SF. Using NGS up to 300 piRNAs were identified in all SF without significant
      differences in expression levels between RA and OASF. Of interest, the analysis
      of the co-expression of the detected piRNAs revealed a less tightly regulated
      pattern of piRNA-823, -4153 and -16659 expression in RASF. In RASF and OASF,
      stimulation with TNFalpha+IL1beta/TLR-ligands further significantly increased the
      expression levels of PIWIL2 and 4 mRNA and piRNA-16659 was significantly (4-fold)
      induced upon Poly(I:C) stimulation. Silencing of PIWIL2/4 neither affect LINE-1
      methylation/expression nor proliferation of RASF. CONCLUSION: We detected a new
      class of small regulatory RNAs (piRNAs) and their specific binding partners
      (PIWIL2/4) in synovial fibroblasts. The differential regulation of co-expression
      of piRNAs in RASF and the induction of piRNA/Piwi-proteins by innate immune
      stimulators suggest a role in inflammatory processes.

PMID- 27893853
TI  - Four Decades of Obesity Trends among Non-Hispanic Whites and Blacks in the United
      States: Analyzing the Influences of Educational Inequalities in Obesity and
      Population Improvements in Education.
AB  - Both obesity (body mass index >= 30) and educational attainment have increased
      dramatically in the United States since the 1970s. This study analyzed the
      influences of educational inequalities in obesity and population improvements in
      education on national obesity trends between 1970 and 2010. For non-Hispanic
      white and black males and females aged 25-74 years, educational differences in
      the probability of being obese were estimated from the 1971-2012 National Health
      and Nutrition Examination Surveys, and population distributions of age and
      educational groups, from the 1970 Census and 2010 American Community Survey. In
      the total population, obesity increased from 15.7% to 38.8%, and there were
      increases in the greater obese probabilities of non-college graduates relative to
      four-year college graduates. The increase in obesity would have been lower by 10%
      (2.2 percentage points) if educational inequalities in obesity had stayed at
      their 1970 values and lower by one third (7.9 points) if obesity inequalities had
      been eliminated. Obesity inequalities were larger for females than males and for
      whites than blacks, and obesity did not differ by education among black males. As
      a result, the impact of obesity inequalities on the obesity trend was largest
      among white females (a 47% reduction in the obesity increase if obesity
      inequalities had been eliminated), and virtually zero among black males. On the
      other hand, without educational improvements, the obesity increase would have
      been 9% more in the total population, 23% more among white females and not
      different in the other three subpopulations. Results indicate that obesity
      inequalities made sizable contributions to the obesity trends, and the obesity
      reductions associated with educational improvements were more limited.

PMID- 27893852
TI  - A Comparative Study of SMN Protein and mRNA in Blood and Fibroblasts in Patients
      with Spinal Muscular Atrophy and Healthy Controls.
AB  - BACKGROUND: Clinical trials to test safety and efficacy of drugs for patients
      with spinal muscular atrophy (SMA) are currently underway. Biomarkers that
      document treatment-induced effects are needed because disease progression in
      childhood forms of SMA is slow and clinical outcome measures may lack sensitivity
      to detect meaningful changes in motor function in the period of 1-2 years of
      follow-up during randomized clinical trials. OBJECTIVE: To determine and compare
      SMN protein and mRNA levels in two cell types (i.e. PBMCs and skin-derived
      fibroblasts) from patients with SMA types 1-4 and healthy controls in relation to
      clinical characteristics and SMN2 copy numbers. MATERIALS AND METHODS: We
      determined SMN1, SMN2-full length (SMN2-FL), SMN2-delta7 (SMN2-Delta7), GAPDH and
      18S mRNA levels and SMN protein levels in blood and fibroblasts from a total of
      150 patients with SMA and 293 healthy controls using qPCR and ELISA. We analyzed
      the association with clinical characteristics including disease severity and
      duration, and SMN2 copy number. RESULTS: SMN protein levels in PBMCs and
      fibroblasts were higher in controls than in patients with SMA (p<0.01).
      Stratification for SMA type did not show differences in SMN protein (p>0.1) or
      mRNA levels (p>0.05) in either cell type. SMN2 copy number was associated with
      SMN protein levels in fibroblasts (p = 0.01), but not in PBMCs (p = 0.06).
      Protein levels in PBMCs declined with age in patients (p<0.01) and controls
      (p<0.01)(power 1-beta = 0.7). Ratios of SMN2-Delta7/SMN2-FL showed a broad range,
      primarily explained by the variation in SMN2-Delta7 levels, even in patients with
      a comparable SMN2 copy number. Levels of SMN2 mRNA did not correlate with SMN2
      copy number, SMA type or age in blood (p = 0.7) or fibroblasts (p = 0.09). Paired
      analysis between blood and fibroblasts did not show a correlation between the two
      different tissues with respect to the SMN protein or mRNA levels. CONCLUSIONS:
      SMN protein levels differ considerably between tissues and activity is age
      dependent in patients and controls. SMN protein levels in fibroblasts correlate
      with SMN2 copy number and have potential as a biomarker for disease severity.

PMID- 27893854
TI  - Dissemination and Mechanism for the MCR-1 Colistin Resistance.
AB  - Polymyxins are the last line of defense against lethal infections caused by
      multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins
      has been greatly challenged by the emergence of the plasmid-borne mobile colistin
      resistance gene (mcr-1). However, the mechanistic aspects of the MCR-1 colistin
      resistance are still poorly understood. Here we report the comparative genomics
      of two new mcr-1-harbouring plasmids isolated from the human gut microbiota,
      highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic
      dissection delineated that both the trans-membrane region and a substrate-binding
      motif are required for the MCR-1-mediated colistin resistance. The soluble form
      of the membrane protein MCR-1 was successfully prepared and verified.
      Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart
      PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact
      that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome
      encoded colistin-resistant Neisseria LptA (EptA) potentially implies parallel
      evolutionary paths for the two genes. In conclusion, our finding provids a first
      glimpse of mechanism for the MCR-1-mediated colistin resistance.

PMID- 27893855
TI  - Inhibition of Matrix Metalloproteinase 9 Enhances Rod Survival in the S334ter
      line3 Retinitis Pigmentosa Model.
AB  - Retinitis Pigmentosa (RP) is one of the most common forms of inherited visual
      loss with the initial degeneration of rod photoreceptors, followed by a
      progressive cone photoreceptor deterioration. Coinciding with this visual loss,
      the extracellular matrix (ECM) is reorganized, which alters matrix
      metalloproteinase (MMP) activity levels. A potential pathological role of MMPs,
      MMP-9 in particular, involves an excitotoxicity-mediated physiological response.
      In the current study, we examine the MMP-9 and MMP-2 expression levels in the
      rhodopsin S334ter-line3 RP rat model and investigate the impact of treatment with
      SB-3CT, a specific MMP-9 and MMP-2 inhibitor, on rod cell survival was tested.
      Retinal MMP-9 and MMP-2 expression levels were quantified by immunoblot analysis
      from S334ter-line3 rats compared to controls. Gelatinolytic activities of MMP-9
      and MMP-2 by zymography were examined. The geometry of rod death was further
      evaluated using Voronoi analysis. Our results revealed that MMP-9 was elevated
      while MMP-2 was relatively unchanged when S334ter-line 3 retinas were compared to
      controls. With SB-3CT treatment, we observed gelatinolytic activity of both MMPs
      was decreased and diminished clustering associated with rod death, in addition to
      a robust preservation of rod photoreceptors. These results demonstrate that up
      regulation of MMP-9 in retinas of S334ter-line3 are associated with rod death.
      The application of SB-3CT dramatically interferes with mechanisms leading to
      apoptosis in an MMP-9-dependent manner. Future studies will determine the
      feasibility of using SB-3CT as a potential therapeutic strategy to slow
      progression of vision loss in genetic inherited forms of human RP.

PMID- 27893856
TI  - Spatial Distribution of Selected Chemical Cell Wall Components in the Embryogenic
      Callus of Brachypodium distachyon.
AB  - Brachypodium distachyon L. Beauv. (Brachypodium) is a species that has become an
      excellent model system for gaining a better understanding of various areas of
      grass biology and improving plant breeding. Although there are some studies of an
      in vitro Brachypodium culture including somatic embryogenesis, detailed knowledge
      of the composition of the main cell wall components in the embryogenic callus in
      this species is missing. Therefore, using the immunocytochemical approach, we
      targeted 17 different antigens of which five were against the arabinogalactan
      proteins (AGP), three were against extensins, six recognised pectic epitopes and
      two recognised hemicelluloses. These studies were complemented by histological
      and scanning electron microscopy (SEM) analyses. We revealed that the
      characteristic cell wall components of Brachypodium embryogenic calli are AGP
      epitopes that are recognised by the JIM16 and LM2 antibodies, an extensin epitope
      that is recognised by the JIM11 antibody and a pectic epitopes that is recognised
      by the LM6 antibody. Furthermore, we demonstrated that AGPs and pectins are the
      components of the extracellular matrix network in Brachypodium embryogenic
      culture. Additionally, SEM analysis demonstrated the presence of an extracellular
      matrix on the surface of the calli cells. In conclusion, the chemical
      compositions of the cell walls and ECMSN of Brachypodium callus show spatial
      differences that correlate with the embryogenic character of the cells. Thus, the
      distribution of pectins, AGPs and hemicelluloses can be used as molecular markers
      of embryogenic cells. The presented data extends the knowledge about the chemical
      composition of the embryogenic callus cells of Brachypodium.

PMID- 27893858
TI  - Reversing Age Related Changes of the Laryngeal Muscles by Chronic
      Electrostimulation of the Recurrent Laryngeal Nerve.
AB  - Age related atrophy of the laryngeal muscles -mainly the thyroarytenoid muscle
      (TAM)- leads to a glottal gap and consequently to a hoarse and dysphonic voice
      that significantly affects quality of life. The aim of our study was to reverse
      this atrophy by inducing muscular hypertrophy by unilateral functional electrical
      stimulation (FES) of the recurrent laryngeal nerve (RLN) in a large animal model
      using aged sheep (n = 5). Suitable stimulation parameters were determined by
      fatiguing experiments of the thyroarytenoid muscle in an acute trial. For the
      chronic trial an electrode was placed around the right RLN and stimulation was
      delivered once daily for 29 days. We chose a very conservative stimulation
      pattern, total stimulation time was two minutes per day, or 0.14% of total time.
      Overall, the mean muscle fiber diameter of the stimulated right TAM was
      significantly larger than the non-stimulated left TAM (30MUm+/-1.1MUm vs. 28MUm+/
      1.1 MUm, p<0.001). There was no significant shift in fiber type distribution as
      judged by immunohistochemistry. The changes of fiber diameter could not be
      observed in the posterior cricoarytenoid muscle (PCAM). FES is a possible new
      treatment option for reversing the effects of age related laryngeal muscle
      atrophy.

PMID- 27893857
TI  - Shear-Wave Elastography for the Differential Diagnosis of Breast Papillary
      Lesions.
AB  - OBJECTIVE: To evaluate the diagnostic performance of shear-wave elastography
      (SWE) for the differential diagnosis of breast papillary lesions. METHODS: This
      study was an institutional review board-approved retrospective study, with a
      waiver of informed consent. A total of 79 breast papillary lesions in 71
      consecutive women underwent ultrasound and SWE prior to biopsy. Ultrasound
      features and quantitative SWE parameters were recorded for each lesion. All
      lesions were surgically excised or excised using an ultrasound-guided vacuum
      assisted method. The diagnostic performances of the quantitative SWE parameters
      were compared using the area under the receiver operating characteristic curve
      (AUC). RESULTS: Of the 79 lesions, six (7.6%) were malignant and 12 (15.2%) were
      atypical. Orientation, margin, and the final BI-RADS ultrasound assessments were
      significantly different for the papillary lesions (p < 0.05). All qualitative SWE
      parameters were significantly different (p < 0.05). The AUC values for SWE
      parameters of benign and atypical or malignant papillary lesions ranged from
      0.707 to 0.757 (sensitivity, 44.4-94.4%; specificity, 42.6-88.5%). The maximum
      elasticity and the mean elasticity showed the highest AUC (0.757) to
      differentiate papillary lesions. CONCLUSION: SWE provides additional information
      for the differential diagnosis of breast papillary lesions. Quantitative SWE
      features were helpful to differentiate breast papillary lesions.

PMID- 27893859
TI  - Hippocampal Calcification on Computed Tomography in Relation to Cognitive Decline
      in Memory Clinic Patients: A Case-Control Study.
AB  - BACKGROUND: It was recently shown that calcification of the hippocampus can be
      detected on computed tomography (CT) images and these calcifications occur in up
      to 20% of people over 50 years of age. However, little is known about hippocampal
      calcification and its relation to cognition and cognitive decline. Therefore, the
      aim of this study was to (1) determine the prevalence of hippocampal
      calcification on CT in memory clinic patients controls, and (2) to assess its
      relation with cognitive decline. METHODS: 67 patients from a memory clinic
      (cases) were matched by age and gender to a control group. In both groups,
      hippocampal calcification was assessed by two raters on thin slice, non-contrast
      enhanced brain CT images. Calcifications were scored bilaterally on presence and
      severity (absent, mild, moderate, severe). Mini Mental State Exam (MMSE) score
      was determined in cases. RESULTS: Hippocampal calcification presence was
      significantly higher in cases (N = 26, 38.8%) compared to controls (N = 9, 13.4%)
      (P < .01) with an odds ratio of 4.40 (95%CI: 1.63-14.87). In cases, MMSE score
      was significantly lower in those with hippocampal calcification compared to those
      without (21.6 vs 24.5, p = .02). CONCLUSION: In this case-control study we found
      significantly more hippocampal calcification in patients with cognitive decline
      as compared to controls. Furthermore, within the cases, MMSE score was
      significantly lower in those with hippocampal calcification.

PMID- 27893861
TI  - Attitudes towards Intimate Partner Violence against Women among Women and Men in
      39 Low- and Middle-Income Countries.
AB  - BACKGROUND: Violence against women perpetrated by an intimate partner (IPV) is
      prevalent in low- and middle-income countries (LAMIC). The aim was to describe
      the attitudes of women and men towards perpetration of physical violence to women
      by an intimate partner, in a large group of low- and middle-income countries.
      METHODS AND FINDINGS: We used data from Round Four of the UNICEF Multiple
      Indicator Cluster Surveys. Attitudes towards IPV against women were assessed by a
      study-specific scale asking if 'wife beating' is justified in any of five
      circumstances. Overall, data from 39 countries (all had data from women and 13
      countries also had data from men) were included in the analyses. The proportions
      of women who held attitudes that 'wife-beating' was justified in any of the five
      circumstances varied widely among countries from 2.0% (95% CI 1.7;2.3) in
      Argentina to 90.2% (95% CI 88.9;91.5) in Afghanistan. Similarly, among men it
      varied from 5.0% (95% CI 4.0;6.0) in Belarus to 74.5% (95% CI 72.5;76.4) in the
      Central African Republic. The belief that 'wife-beating' is acceptable was most
      common in Africa and South Asia, and least common in Central and Eastern Europe
      and Latin America and the Caribbean. In general this belief was more common among
      people in disadvantaged circumstances, including being a member of a family in
      the lowest household wealth quintile, living in a rural area and having limited
      formal education. Young adults were more likely to accept physical abuse by a man
      of his intimate partner than those who were older, but people who had never
      partnered were less likely to have these attitudes. CONCLUSIONS: Violence against
      women is an international priority and requires a multicomponent response. These
      data provide evidence that strategies should include major public education
      programs to change attitudes about the acceptability of IPV against women, and
      that these should be addressed to women and girls as well as to boys and men.

PMID- 27893860
TI  - Blocking Synthesis of the Variant Surface Glycoprotein Coat in Trypanosoma brucei
      Leads to an Increase in Macrophage Phagocytosis Due to Reduced Clearance of
      Surface Coat Antibodies.
AB  - The extracellular bloodstream form parasite Trypanosoma brucei is supremely
      adapted to escape the host innate and adaptive immune system. Evasion is mediated
      through an antigenically variable Variant Surface Glycoprotein (VSG) coat, which
      is recycled at extraordinarily high rates. Blocking VSG synthesis triggers a
      precytokinesis arrest where stalled cells persist for days in vitro with
      superficially intact VSG coats, but are rapidly cleared within hours in mice. We
      therefore investigated the role of VSG synthesis in trypanosome phagocytosis by
      activated mouse macrophages. T. brucei normally effectively evades macrophages,
      and induction of VSG RNAi resulted in little change in phagocytosis of the
      arrested cells. Halting VSG synthesis resulted in stalled cells which swam
      directionally rather than tumbling, with a significant increase in swim velocity.
      This is possibly a consequence of increased rigidity of the cells due to a
      restricted surface coat in the absence of VSG synthesis. However if VSG RNAi was
      induced in the presence of anti-VSG221 antibodies, phagocytosis increased
      significantly. Blocking VSG synthesis resulted in reduced clearance of anti-VSG
      antibodies from the trypanosome surface, possibly as a consequence of the changed
      motility. This was particularly marked in cells in the G2/ M cell cycle stage,
      where the half-life of anti-VSG antibody increased from 39.3 +/- 4.2 seconds to
      99.2 +/- 15.9 seconds after induction of VSG RNAi. The rates of internalisation
      of bulk surface VSG, or endocytic markers like transferrin, tomato lectin or
      dextran were not significantly affected by the VSG synthesis block. Efficient
      elimination of anti-VSG-antibody complexes from the trypanosome cell surface is
      therefore essential for trypanosome evasion of macrophages. These experiments
      highlight the essentiality of high rates of VSG recycling for the rapid removal
      of host opsonins from the parasite surface, and identify this process as a key
      parasite virulence factor during a chronic infection.

PMID- 27893863
TI  - High Vitamin D Consumption Is Inversely Associated with Cardiovascular Disease
      Risk in an Urban Mexican Population.
AB  - BACKGROUND: Vitamin D deficiency is a major global public health problem. Recent
      epidemiological studies have assessed the relationship between vitamin D and
      multiple outcomes, including cardiovascular disease. However, this evidence is
      limited and inconclusive. Our purpose in this study was to evaluate the
      association between dietary vitamin D intake and cardiovascular disease risk in
      adult Mexican population. METHODS: We conducted a cross-sectional analysis with
      the baseline data from 6294 men and women aged 20-80 years participating in the
      Health Workers Cohort Study. Data on sociodemographic, lifestyle, and medical
      history factors were collected with a self-administered questionnaire. Dietary
      intake was evaluated by using a semi-quantitative food-frequency questionnaire.
      Cardiovascular disease risk was calculated using a recalibration of the
      Framingham heart disease prediction score. To evaluate the association between
      vitamin D intake and 10-year cardiovascular disease risk, odds ratios (OR) and
      95% confidence intervals (95% CI) were calculated using multiple logistic
      regression analysis. RESULTS: A total of 6294 subjects (1820 men and 4474 women)
      with a mean age of 42 years, were included. Of these, subjects in the highest
      quintile of vitamin D intake presented lower levels of triglycerides 14.6 mg/dL
      (P for trend = 0.001); 2.0 cm less in waist circumference (P for trend = 0.001)
      and 0.8 points less in the Framingham cardiovascular disease risk score (P for
      trend = 0.002) compared with the subjects in the lower quintile of vitamin D
      intake. Additionally, participants in the highest quintile of vitamin D
      consumption were less likely to develop elevated 10-year cardiovascular disease
      risk, compared with those in the lowest quintile (OR = 0.51; 95%CI: 0.33, 0.77; P
      for trend = 0.007). CONCLUSION: Our data suggest that higher consumption of
      vitamin D is associated with a reduced risk of cardiovascular disease in Mexican
      population.

PMID- 27893862
TI  - Diversity and Evolutionary Analysis of Iron-Containing (Type-III) Alcohol
      Dehydrogenases in Eukaryotes.
AB  - BACKGROUND: Alcohol dehydrogenase (ADH) activity is widely distributed in the
      three domains of life. Currently, there are three non-homologous NAD(P)+
      dependent ADH families reported: Type I ADH comprises Zn-dependent ADHs; type II
      ADH comprises short-chain ADHs described first in Drosophila; and, type III ADH
      comprises iron-containing ADHs (FeADHs). These three families arose independently
      throughout evolution and possess different structures and mechanisms of reaction.
      While types I and II ADHs have been extensively studied, analyses about the
      evolution and diversity of (type III) FeADHs have not been published yet.
      Therefore in this work, a phylogenetic analysis of FeADHs was performed to get
      insights into the evolution of this protein family, as well as explore the
      diversity of FeADHs in eukaryotes. PRINCIPAL FINDINGS: Results showed that FeADHs
      from eukaryotes are distributed in thirteen protein subfamilies, eight of them
      possessing protein sequences distributed in the three domains of life.
      Interestingly, none of these protein subfamilies possess protein sequences found
      simultaneously in animals, plants and fungi. Many FeADHs are activated by or
      contain Fe2+, but many others bind to a variety of metals, or even lack of metal
      cofactor. Animal FeADHs are found in just one protein subfamily, the hydroxyacid
      oxoacid transhydrogenase (HOT) subfamily, which includes protein sequences widely
      distributed in fungi, but not in plants), and in several taxa from lower
      eukaryotes, bacteria and archaea. Fungi FeADHs are found mainly in two
      subfamilies: HOT and maleylacetate reductase (MAR), but some can be found also in
      other three different protein subfamilies. Plant FeADHs are found only in
      chlorophyta but not in higher plants, and are distributed in three different
      protein subfamilies. CONCLUSIONS/SIGNIFICANCE: FeADHs are a diverse and ancient
      protein family that shares a common 3D scaffold with a patchy distribution in
      eukaryotes. The majority of sequenced FeADHs from eukaryotes are distributed in
      just two subfamilies, HOT and MAR (found mainly in animals and fungi). These two
      subfamilies comprise almost 85% of all sequenced FeADHs in eukaryotes.

PMID- 27893864
TI  - Cost-Effectiveness of the 'One4All' HIV Linkage Intervention in Guangxi Zhuang
      Autonomous Region, China.
AB  - BACKGROUND: In Guangxi Zhuang Autonomous Region, China, an estimated 80% of newly
      identified antiretroviral therapy (ART)-eligible patients are not engaged in ART.
      Delayed ART uptake ultimately translates into high rates of HIV morbidity,
      mortality, and transmission. To enhance HIV testing receipt and subsequent
      treatment uptake in Guangxi, the Chinese Center for Disease Control and
      Prevention (CDC) executed a cluster-randomized trial to assess the effectiveness
      and cost-effectiveness of a streamlined HIV testing algorithm (the One4All
      intervention) in 12 county-level hospitals. OBJECTIVE: To determine the
      incremental cost-effectiveness of the One4All intervention delivered at county
      hospitals in Guangxi, China, compared to the current standard of care (SOC).
      PERSPECTIVE: Health System. TIME HORIZON: 1-, 5-and 25-years. METHODS: We adapted
      a dynamic, compartmental HIV transmission model to simulate HIV transmission and
      progression in Guangxi, China and identify the economic impact and health
      benefits of implementing the One4All intervention in all Guangxi hospitals. The
      One4All intervention algorithm entails rapid point-of-care HIV screening, CD4 and
      viral load testing of individuals presenting for HIV screening, with same-day
      results and linkage to counselling. We populated the model with data from the
      One4All trial (CTN-0056), China CDC HIV registry and published reports. Model
      outcomes were HIV incidence, mortality, costs, quality-adjusted life years
      (QALYs), and the incremental cost-effectiveness ratio (ICER) of the One4All
      intervention compared to SOC. RESULTS: The One4All testing intervention was more
      costly than SOC (CNY 2,182 vs. CNY 846), but facilitated earlier ART access,
      resulting in delayed disease progression and mortality. Over a 25-year time
      horizon, we estimated that introducing One4All in Guangxi would result in 802
      averted HIV cases and 1629 averted deaths at an ICER of CNY 11,678 per QALY
      gained. Sensitivity analysis revealed that One4All remained cost-effective at
      even minimal levels of effectiveness. Results were robust to changes to a range
      of parameters characterizing the HIV epidemic over time. CONCLUSIONS: The One4All
      HIV testing strategy was highly cost-effective by WHO standards, and should be
      prioritized for widespread implementation in Guangxi, China. Integrating the
      intervention within a broader combination prevention strategy would enhance the
      public health response to HIV/AIDS in Guangxi.

PMID- 27893865
TI  - The Decrease in Traumatic Brain Injury Epidemics Deriving from Road Traffic
      Collision Following Strengthened Legislative Measures in France.
AB  - BACKGROUND: Since 2002, France has been strengthening legislation on road
      traffic. This study is intended to evaluate the changes in Traumatic Brain Injury
      (TBI) incidence and mortality resulting from Road Traffic Collision (RTC) in the
      two 6-year periods before and after 2002. METHODS: We used a Registry of all RTC
      casualties in the Rhone Department of France. Each casualty was coded according
      to the Abbreviated Injury Scale (AIS). The study describes changes in demographic
      variables, TBI (AIS >= 2) incidence and mortality, other body lesions (AIS >= 3)
      associated with TBI, road user types, seatbelt and helmet wearing. FINDINGS: RTC
      casualty occurrences decreased by 21% (from 64,312 to 50,746) during the period
      after 2002. TBI occurrence accounted for 8.6% and 6.7% of all RTC in both
      periods. This corresponds to a reduction of TBI casualty incidence (-42%), which
      was much more pronounced than RTC casualty incidence (-25%) (p < 0.0001). Severe
      and critical TBI (AIS-4 and -5) incidences were reduced by half as much (-21%),
      compared to TBI incidence. TBI mortality rate (among population) and lethality
      (among TBI related to RTC casualties) decreased 56% and 23%, respectively. This
      reduction particularly affected car occupants and victims who deceased. TBI
      incidence decreased 43% in all 10-year age classes until 60 on average, this
      decrease declining with age in the period after 2002. After adjustment for age,
      sex, road user types, and severity of lesions at the head and other body regions,
      logistic regression analysis displayed a protective effect of the period
      following 2002, on the risk of death after RTC-related TBI. INTERPRETATION: The
      greater reductions in the incidence, severity and mortality of TBI when compared
      with the reduction of casualty incidence have mainly affected car users. These
      results should be attributable to the improvements in standards of care, primary
      safety of the car fleet and general road architecture safety. However, the
      increased reduction in the TBI epidemics in France, when compared to those
      observed in other developed countries for the same periods, suggests that the
      effects should be strongly attributable to changes in road user behaviour induced
      by law enforcement. The at-risk groups for TBI after RTC are now two-wheel users
      (motorized or not) and individuals over 60 years of age.

PMID- 27893866
TI  - Ecology and Demography of Free-Roaming Domestic Dogs in Rural Villages near
      Serengeti National Park in Tanzania.
AB  - Free-roaming dogs (Canis lupus familiaris) are of public health and conservation
      concern because of their potential to transmit diseases, such as rabies, to both
      people and wildlife. Understanding domestic dog population dynamics and how they
      could potentially be impacted by interventions, such as rabies vaccination, is
      vital for such disease control efforts. For four years, we measured demographic
      data on 2,649 free-roaming domestic dogs in four rural villages in Tanzania: two
      villages with and two without a rabies vaccination campaign. We examined the
      effects of body condition, sex, age and village on survivorship and reproduction.
      Furthermore, we compared sources of mortality among villages. We found that adult
      dogs (>12mos) had higher survival than puppies in all villages. We observed a
      male-biased sex ratio across all age classes. Overall survival in one non
      vaccination village was lower than in the other three villages, all of which had
      similar survival probabilities. In all villages, dogs in poor body condition had
      lower survival than dogs in ideal body condition. Sickness and spotted hyena
      (Crocuta crocuta) predation were the two main causes of dog death. Within
      vaccination villages, vaccinated dogs had higher survivorship than unvaccinated
      dogs. Dog population growth, however, was similar in all the villages suggesting
      village characteristics and ownership practices likely have a greater impact on
      overall dog population dynamics than vaccination. Free-roaming domestic dogs in
      rural communities exist in the context of their human owners as well as the
      surrounding wildlife. Our results did not reveal a clear effect of vaccination
      programs on domestic dog population dynamics. An investigation of the role of
      dogs and their care within these communities could provide additional insight for
      planning and implementing rabies control measures such as mass dog vaccination.

PMID- 27893867
TI  - The Development of Diabetes after Subtotal Gastrectomy with Billroth II
      Anastomosis for Peptic Ulcer Disease.
AB  - PURPOSE: A duodenal bypass after a Roux-en-Y gastric bypass operation for obesity
      can ameliorate the development of diabetes mellitus (DM). We attempted to
      determine the subsequent risk of developing DM after subtotal gastrectomy with
      Billroth II anastomosis (SGBIIA) for peptic ulcer disease (PUD). METHODS: We
      identified 662 patients undergoing SGBIIA for PUD between 2000 and 2011 from the
      Longitudinal Health Insurance Database as the study cohort, and we randomly
      selected 2647 controls from the peptic ulcer population not undergoing SGBIIA and
      were frequency-matched by age, sex, and index year for the control cohort. All
      patient cases in both cohorts were followed until the end of 2011 to measure the
      incidence of DM. We analyzed DM risk by using a Cox proportional hazards
      regression model. RESULTS: The patients who underwent SGBIIA demonstrated a lower
      cumulative incidence of DM compared with the control cohort (log-rank test, P <
      .001 and 6.73 vs 12.6 per 1000 person-y). The difference in the DM risk between
      patients with and without SGBIIA increased gradually with the follow-up duration.
      Age and sex did not affect the subsequent risk of developing DM, according to the
      multivariable Cox regression model. Nevertheless, the SGBIIA cohort exhibited a
      lower DM risk after we adjusted for the comorbidities of hypertension,
      hyperlipidemia, and coronary artery disease (adjusted hazard ratio (aHR): 0.56,
      95% confidence interval (CI): 0.40-0.78). The incidence rate ratio (IRR) of DM in
      the SGBIIA cohort was lower than that in the control cohort for all age groups
      (age <= 49 y, IRR: 0.40, 95% CI: 0.16-0.99; age 50-64 y, IRR: 0.54, 95% CI: 0.31
      0.96; age ? 65 y, IRR: 0.57, 95% CI: 0.36-0.91). Moreover, the IRR of DM was
      significantly lower in the SGBIIA cohort with comorbidities (IRR: 0.50, 95% CI:
      0.31-0.78) compared with those without a comorbidity (IRR: 0.65, 95% CI: 0.40
      1.04). CONCLUSION: The findings of this population-based cohort study revealed
      that SGBIIA was associated with a reduced risk of DM development, and the inverse
      association was greater in the presence of a comorbidity.

PMID- 27893869
TI  - Why Are Prospective Longitudinal Studies Needed in Preterm Behavioral Epigenetic
      Research?

PMID- 27893868
TI  - Three Boundary Conditions for Computing the Fixed-Point Property in Binary
      Mixture Data.
AB  - The notion of "mixtures" has become pervasive in behavioral and cognitive
      sciences, due to the success of dual-process theories of cognition. However,
      providing support for such dual-process theories is not trivial, as it crucially
      requires properties in the data that are specific to mixture of cognitive
      processes. In theory, one such property could be the fixed-point property of
      binary mixture data, applied-for instance- to response times. In that case, the
      fixed-point property entails that response time distributions obtained in an
      experiment in which the mixture proportion is manipulated would have a common
      density point. In the current article, we discuss the application of the fixed
      point property and identify three boundary conditions under which the fixed-point
      property will not be interpretable. In Boundary condition 1, a finding in support
      of the fixed-point will be mute because of a lack of difference between
      conditions. Boundary condition 2 refers to the case in which the extreme
      conditions are so different that a mixture may display bimodality. In this case,
      a mixture hypothesis is clearly supported, yet the fixed-point may not be found.
      In Boundary condition 3 the fixed-point may also not be present, yet a mixture
      might still exist but is occluded due to additional changes in behavior. Finding
      the fixed-property provides strong support for a dual-process account, yet the
      boundary conditions that we identify should be considered before making
      inferences about underlying psychological processes.

PMID- 27893871
TI  - Why Are Prospective Longitudinal Studies Needed in Preterm Behavioral Epigenetic
      Research?-Reply.

PMID- 27893870
TI  - Associations Between Hydration Status, Intravenous Fluid Administration, and
      Outcomes of Patients Infected With Shiga Toxin-Producing Escherichia coli: A
      Systematic Review and Meta-analysis.
AB  - Importance: The associations between hydration status, intravenous fluid
      administration, and outcomes of patients infected with Shiga toxin-producing
      Escherichia coli (STEC) remain unclear. Objective: To determine the relationship
      between hydration status, the development and severity of hemolytic uremic
      syndrome (HUS), and adverse outcomes in STEC-infected individuals. Data Sources:
      MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP
      platform, PubMed via the National Library of Medicine, CINAHL Plus with full
      text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray
      literature were systematically searched. Study Selection: Two reviewers
      independently identified studies that included patients with hydration status
      documentation, proven or presumed STEC infection, and some form of HUS that
      developed. No language restrictions were applied. Data Extraction and Synthesis:
      Two reviewers independently extracted individual study data, including study
      characteristics, population, and outcomes. Risk of bias was assessed using the
      Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of
      Recommendations Assessment, Development, and Evaluation method. Meta-analyses
      were conducted using random-effects models. Main Outcomes and Measures:
      Development of HUS, complications (ie, oligoanuric renal failure, involvement of
      the central nervous system, or death), and interventions (ie, renal replacement
      therapy). Results: Eight studies comprising 1511 patients (all children) met
      eligibility criteria. Unpublished data were provided by the authors of 7
      published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies
      evaluated the effect of hydration during STEC infections on the risk for HUS. A
      hematocrit value greater than 23% as a measure of hydration status at
      presentation with HUS was associated with the development of oligoanuric HUS (OR,
      2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI,
      1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%).
      Compared with putatively hydrated patients, clinically dehydrated patients had an
      OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid
      administration up to the day of HUS diagnosis was associated with a decreased
      risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]). Conclusions and
      Relevance: Two predictors of poor outcomes for STEC-infected children were
      identified: (1) the lack of intravenous fluid administration prior to
      establishment of HUS and (2) a higher hematocrit value at presentation. These
      findings point to an association between dehydration and adverse outcomes for
      children with HUS.

PMID- 27893872
TI  - Intra-arterial Treatment for Basilar Artery Occlusion.

PMID- 27893873
TI  - Association of Cerebrospinal Fluid Ferritin Level With Preclinical Cognitive
      Decline in APOE-epsilon4 Carriers.

PMID- 27893875
TI  - Can Sustained Glia-Mediated Brain Inflammation After Repeated Concussive Brain
      Injury Be Detected In Vivo?

PMID- 27893874
TI  - Association of Perivascular Localization of Aquaporin-4 With Cognition and
      Alzheimer Disease in Aging Brains.
AB  - Importance: Cognitive impairment and dementia, including Alzheimer disease (AD),
      are common within the aging population, yet the factors that render the aging
      brain vulnerable to these processes are unknown. Perivascular localization of
      aquaporin-4 (AQP4) facilitates the clearance of interstitial solutes, including
      amyloid-beta, through the brainwide network of perivascular pathways termed the
      glymphatic system, which may be compromised in the aging brain. Objectives: To
      determine whether alterations in AQP4 expression or loss of perivascular AQP4
      localization are features of the aging human brain and to define their
      association with AD pathology. Design, Setting, and Participants: Expression of
      AQP4 was analyzed in postmortem frontal cortex of cognitively healthy and
      histopathologically confirmed individuals with AD by Western blot or
      immunofluorescence for AQP4, amyloid-beta 1-42, and glial fibrillary acidic
      protein. Postmortem tissue and clinical data were provided by the Oregon Health
      and Science University Layton Aging and Alzheimer Disease Center and Oregon Brain
      Bank. Postmortem tissue from 79 individuals was evaluated, including cognitively
      intact "young" individuals aged younger than 60 years (range, 33-57 years),
      cognitively intact "aged" individuals aged older than 60 years (range, 61-96
      years) with no known neurological disease, and individuals older than 60 years
      (range, 61-105 years) of age with a clinical history of AD confirmed by
      histopathological evaluation. Forty-eight patient samples (10 young, 20 aged, and
      18 with AD) underwent histological analysis. Sixty patient samples underwent
      Western blot analysis (15 young, 24 aged, and 21 with AD). Main Outcomes and
      Measures: Expression of AQP4 protein, AQP4 immunoreactivity, and perivascular
      AQP4 localization in the frontal cortex were evaluated. Results: Expression of
      AQP4 was associated with advancing age among all individuals (R2 = 0.17; P =
      .003). Perivascular AQP4 localization was significantly associated with AD status
      independent of age (OR, 11.7 per 10% increase in localization; z = -2.89; P =
      .004) and was preserved among eldest individuals older than 85 years of age who
      remained cognitively intact. When controlling for age, loss of perivascular AQP4
      localization was associated with increased amyloid-beta burden (R2 = 0.15; P =
      .003) and increasing Braak stage (R2 = 0.14; P = .006). Conclusions and
      Relevance: In this study, altered AQP4 expression was associated with aging
      brains. Loss of perivascular AQP4 localization may be a factor that renders the
      aging brain vulnerable to the misaggregation of proteins, such as amyloid-beta,
      in neurodegenerative conditions such as AD.

PMID- 27893876
TI  - Imaging the Acute Formation of a Cortical Microbleed in Cerebral Amyloid
      Angiopathy.

PMID- 27893877
TI  - Intra-arterial Treatment for Basilar Artery Occlusion-Reply.

PMID- 27893878
TI  - The Affordable Care Act: Moving Forward in the Coming Years.

PMID- 27893879
TI  - The Complexities of Conducting Research on Child Trafficking.

PMID- 27893881
TI  - Ultra-High-Dose Opioids With Low Efficacy and Significant Harm-Time to Make a
      Change: A Teachable Moment.

PMID- 27893882
TI  - The Future of the ACA and Health Care Policy in the United States.

PMID- 27893880
TI  - Protective Prevention Effects on the Association of Poverty With Brain
      Development.
AB  - Importance: This study was designed to determine whether a preventive
      intervention focused on enhancing supportive parenting could ameliorate the
      association between exposure to poverty and brain development in low
      socioeconomic status African American individuals from the rural South.
      Objective: To determine whether participation in an efficacious prevention
      program designed to enhance supportive parenting for rural African American
      children will ameliorate the association between living in poverty and reduced
      hippocampal and amygdalar volumes in adulthood. Design, Setting, and
      Participants: In the rural southeastern United States, African American parents
      and their 11-year-old children were assigned randomly to the Strong African
      American Families randomized prevention trial or to a control condition. Parents
      provided data used to calculate income-to-needs ratios when children were aged 11
      to 13 years and 16 to 18 years. When the participants were aged 25 years,
      hippocampal and amygdalar volumes were measured using magnetic resonance imaging.
      Exposures: Household poverty was measured by income-to-needs ratios. Main
      Outcomes and Measures: Young adults' whole hippocampal, dentate gyrus, and CA3
      hippocampal subfields as well as amygdalar volumes were assessed using magnetic
      resonance imaging. Results: Of the 667 participants in the Strong African
      American Families randomized prevention trial, 119 right-handed African American
      individuals aged 25 years living in rural areas were recruited. Years lived in
      poverty across ages 11 to 18 years forecasted diminished left dentate gyrus
      (simple slope, -14.20; standard error, 5.22; P = .008) and CA3 (simple slope, 
      6.42; standard error, 2.42; P = .009) hippocampal subfields and left amygdalar
      (simple slope, -34.62; standard error, 12.74; P = .008) volumes among young
      adults in the control condition (mean [SD] time, 2.04 [1.88] years) but not among
      those who participated in the Strong African American Families program (mean [SD]
      time, 2.61 [1.77] years). Conclusions and Relevance: In this study, we described
      how participation in a randomized clinical trial designed to enhance supportive
      parenting ameliorated the association of years lived in poverty with left dentate
      gyrus and CA3 hippocampal subfields and left amygdalar volumes. These findings
      are consistent with a possible role for supportive parenting and suggest a
      strategy for narrowing social disparities.

PMID- 27893883
TI  - Use of Magnetic Resonance Imaging to Visualize Leptomeningeal Inflammation in
      Patients With Multiple Sclerosis: A Review.
AB  - Importance: Multiple sclerosis (MS) is a chronic demyelinating disease of the
      central nervous system traditionally characterized by an initial relapsing
      remitting clinical course and focal inflammatory lesions that have a predilection
      for the periventricular white matter. Recently, however, histopathologic and
      imaging studies have illustrated a more complex pathologic substrate involving
      cortical demyelination, gray matter atrophy, and meningeal inflammation.
      Neuroimaging advances have facilitated improved detection of cortical pathology,
      but our understanding of the pathogenesis of cortical disease remains incomplete.
      The purpose of this review is to evaluate the current status and future prospects
      regarding the emerging role of magnetic resonance imaging to visualize
      leptomeningeal enhancement in patients with MS and place these findings in the
      proper pathobiologic and clinical context. Observations: Cortical atrophy and
      demyelination along the subpial surface appear early in the disease course in
      patients with MS but accelerate in progressive stages. Histopathologic studies of
      patients have shown the presence of inflammatory infiltrates, in some cases with
      features of B cell-rich tertiary lymph follicles, along the cortical meningeal
      surface. Recent magnetic resonance imaging data demonstrate the ability to detect
      such inflammation using high-resolution gadolinium-enhanced contrast scans by the
      presence of leptomeningeal enhancement. Clinical and magnetic resonance imaging
      correlation studies indicate that leptomeningeal enhancement is most common in
      patients with progressive forms of MS and shows a relationship to subpial
      cortical lesions and cortical atrophy. Conclusions and Relevance: A growing body
      of evidence suggests that gray matter demyelination, cortical atrophy, and
      leptomeningeal inflammation may be important components of progressive MS
      pathology and provide a new therapeutic target. Leptomeningeal enhancement may
      prove a useful surrogate marker for such pathology, perhaps improving our
      understanding of the natural history of progressive MS, although its ultimate
      effect on therapeutic development and clinical care requires further study.

PMID- 27893885
TI  - Supporting Family Decision Makers for Nursing Home Residents: A Promising
      Approach.

PMID- 27893884
TI  - Effect of the Goals of Care Intervention for Advanced Dementia: A Randomized
      Clinical Trial.
AB  - Importance: In advanced dementia, goals of care decisions are challenging and
      medical care is often more intensive than desired. Objective: To test a goals of
      care (GOC) decision aid intervention to improve quality of communication and
      palliative care for nursing home residents with advanced dementia. Design,
      Setting, and Participants: A single-blind cluster randomized clinical trial,
      including 302 residents with advanced dementia and their family decision makers
      in 22 nursing homes. Interventions: A GOC video decision aid plus a structured
      discussion with nursing home health care providers; attention control with an
      informational video and usual care planning. Main Outcomes and Measures: Primary
      outcomes at 3 months were quality of communication (QOC, questionnaire scored 0
      10 with higher ratings indicating better quality), family report of concordance
      with clinicians on the primary goal of care (endorsing same goal as the "best
      goal to guide care and medical treatment," and clinicians' "top priority for care
      and medical treatment"), and treatment consistent with preferences (Advance Care
      Planning Problem score). Secondary outcomes at 9 months were family ratings of
      symptom management and care, palliative care domains in care plans, Medical
      Orders for Scope of Treatment (MOST) completion, and hospital transfers. Resident
      family dyads were the primary unit of analysis, and all analyses used intention
      to-treat assignment. Results: Residents' mean age was 86.5 years, 39 (12.9%) were
      African American, and 246 (81.5%) were women. With the GOC intervention, family
      decision makers reported better quality of communication (QOC, 6.0 vs 5.6; P =
      .05) and better end-of-life communication (QOC end-of-life subscale, 3.7 vs 3.0;
      P = .02). Goal concordance did not differ at 3 months, but family decision makers
      with the intervention reported greater concordance by 9 months or death (133
      [88.4%] vs 108 [71.2%], P = .001). Family ratings of treatment consistent with
      preferences, symptom management, and quality of care did not differ. Residents in
      the intervention group had more palliative care content in treatment plans (5.6
      vs 4.7, P = .02), MOST order sets (35% vs 16%, P = .05), and half as many
      hospital transfers (0.078 vs 0.163 per 90 person-days; RR, 0.47; 95% CI, 0.26
      0.88). Survival at 9 months was unaffected (adjusted hazard ratio [aHR], 0.76;
      95% CI, 0.54-1.08; P = .13). Conclusions and Relevance: The GOC decision aid
      intervention is effective to improve end-of-life communication for nursing home
      residents with advanced dementia and enhance palliative care plans while reducing
      hospital transfers. Trial Registration: clinicaltrials.gov Identifier:
      NCT01565642.

PMID- 27893886
TI  - Integrin alpha5beta1 Inhibition by CLT-28643 Reduces Postoperative Wound Healing
      in a Mouse Model of Glaucoma Filtration Surgery.
AB  - Purpose: To evaluate the therapeutic potential of the small molecule integrin
      alpha5beta1 inhibitor, CLT-28643, to improve the filtering surgery outcome in a
      mouse model. Different dose regimens and administration routes of the inhibitor
      were compared with mitomycin C (MMC), the gold standard in clin ical practice.
      Methods: The efficacy of CLT-28643 on surgical outcome was studied in a mouse
      model for filtering surgery (n = 40 eyes from 20 mice per group). Single and
      repeated subconjunctival (SCJ) injections (1 or 2 MUg) and topical eye drops (10
      MUg) of the integrin inhibitor were compared with 2-minute administration of MMC
      0.02%. Bleb size, survival, and signs of toxicity were examined until 28 days
      after surgery. Immunohistochemical analysis of angiogenesis, inflammation,
      collagen deposition, and integrin alpha5beta1 expression were performed on
      postoperative days 3, 8, 14, and 28. A masked observer performed all the
      assessments. Results: Immunostaining showed that integrin alpha5beta1 was highly
      expressed in the bleb at early time-points after surgery and that CLT-28643
      inhibited this upregulation. Efficacy was shown to be dose-dependent for the
      integrin inhibitor CLT-28643 for bleb area and survival, and the wound healing
      process. While 2-MUg single injection of CLT-28643 improved bleb characteristics
      in a similar way as 10-MUg administered by eye drops and MMC, repeated injections
      of 2 MUg showed superior efficacy compared to MMC, with no corneal toxicity.
      Conclusions: Administration of the integrin alpha5beta1 inhibitor CLT-28643 has
      therapeutic potential as an adjunct to glaucoma surgery, possibly with a superior
      efficacy and tolerability compared with MMC when used at the optimal dose.

PMID- 27893887
TI  - Retinal Neurodegeneration in Diabetic Patients Without Diabetic Retinopathy.
AB  - Purpose: To compare the thickness of all retinal layers between a nondiabetic
      group and diabetic patients without diabetic retinopathy (DR). Methods: Cross
      sectional study, in which all subjects underwent an ophthalmic examination
      including optical coherence tomography. After automatic retinal segmentation,
      each retinal layer thickness (eight separate layers and overall thickness) was
      calculated in all nine Early Treatment Diabetic Retinopathy Study (ETDRS) areas.
      The choroidal thickness (CT) also was measured at five locations. Generalized
      additive regression models were used to analyze the data. Results: A total of 175
      patients were recruited, 50 nondiabetic subjects and 125 diabetic patients
      without DR, stratified into three groups according to diabetes duration: group I
      (<5 years, n = 55), group II (5-10 years, n = 39), and group III (>10 years, n =
      31). Overall, groups I and III of diabetic patients had a decrease in the
      photoreceptor layer (PR) thickness, when compared with the nondiabetic subjects
      in six ETDRS areas (P < 0.0007). Patients with more recent diagnosis (group I)
      had thinner PR than those with moderate duration (group II). Interestingly,
      patients with longer known disease (group III) had the thinnest PR values. There
      were no overall differences in the remaining retinal parameters. Conclusions:
      Retinal thickness profile is not linear throughout disease duration. Even in the
      absence of funduscopic disease, PR layer in diabetic patients seems to differ
      from nondiabetic subjects, thus suggesting that some form of neurodegeneration
      may take place before clinical signs of vascular problems arise.

PMID- 27893888
TI  - Potential Neuroprotective Effects of an LSD1 Inhibitor in Retinal Ganglion Cells
      via p38 MAPK Activity.
AB  - Purpose: The epigenetic mechanisms associated with ocular neurodegenerative
      diseases remain unclear. The present study aimed to determine the role of lysine
      specific demethylase 1 (LSD1), which represses transcription by removing the
      methyl group from methylated lysine 4 of histone H3, in retinal ganglion cell
      (RGC) survival, and to investigate the details of the neuroprotective mechanism
      of tranylcypromine, a major LSD1 inhibitor. Methods: The authors evaluated
      whether tranylcypromine contributes to neuronal survival following stress-induced
      damage using primary cultured rat RGCs and in vivo N-methyl-D-aspartate (NMDA)
      induced excitotoxicity. Additionally, the molecules associated with
      tranylcypromine treatment were assessed by microarray and immunoblot analysis.
      Results: Tranylcypromine significantly suppressed neuronal cell death following
      glutamate neurotoxicity and oxidative stress. Microarray and immunoblot analyses
      revealed that p38 mitogen-activated protein kinase (MAPK)gamma was a key molecule
      involved in the neuroprotective mechanisms induced by tranylcypromine because the
      significant suppression of p38 MAPKgamma by glutamate was reversed by
      tranylcypromine. Moreover, although pharmacologic inhibition of the
      phosphorylation of the total p38 MAPKs interfered with neuroprotective effects of
      tranylcypromine, the specific inhibition of p38 MAPKalpha and p38 MAPKbeta did
      not influence RGC survival. This suggests that the non-p38 MAPKalpha/beta
      isoforms have important roles in neuronal survival by tranylcypromine.
      Additionally, the intravitreal administration of tranylcypromine significantly
      saved RGC numbers in an in vivo glaucoma model employing NMDA-induced
      excitotoxicity. Conclusions: These findings indicate that tranylcypromine-induced
      transcriptional and epigenetic regulation modulated RGC survival via the
      promotion of p38 MAPKgamma activity. Therefore, pharmacologic treatments that
      suppress LSD1 activity may be a novel therapeutic strategy that can be used to
      treat neurodegenerative diseases.

PMID- 27893889
TI  - A Monte Carlo Analysis of Error Associated With Two-Wavelength Algorithms for
      Retinal Oximetry.
AB  - Purpose: Two-wavelength algorithms aimed at the extrapolation of retinal
      vasculature optical properties are being used in the clinical setting. Although
      robust, this approach has some clear mathematical limitations. We have conducted
      an in-depth study of this methodology and report on the limits and benefit of
      this approach. Methods: We used a well-tested, voxel-based Monte Carlo model of
      light transfer into biological tissue combined with a seven-layer model of the
      human fundus to create reflectance maps of retina vessels at different
      oxygenation levels. Results: This study shows that the two-wavelength approach
      works remarkably well in the optimal scenario of known calibration arteries and
      veins. Errors as a result of choroidal pigmentation and discrepancies in vessel
      size can be minimized with numerical approaches. When the calibration process
      deviates largely from physiological values, the technique fails with large
      errors. Conclusions: The two-wavelength approach is convenient, easy to
      implement, and suitable in studies where relative rather than absolute knowledge
      of retinal oximetry is necessary. A robust calibration step is paramount when
      using this approach.

PMID- 27893890
TI  - Alternating QRS Complex Morphologic Characteristics in a Man Presenting With
      Scrotal Edema.

PMID- 27893892
TI  - Gun Violence and Firearm Safety in Medical School Curricula: Missed Opportunities
      to Improve Patient Health.

PMID- 27893891
TI  - Avoiding Hospitalizations From Nursing Homes for Potentially Burdensome Care:
      Results of a Qualitative Study.

PMID- 27893893
TI  - Relationship Between Stress Rankings and the Overall Hospital Star Ratings: An
      Analysis of 150 Cities in the United States.

PMID- 27893894
TI  - Face exploration dynamics differentiate men and women.
AB  - The human face is central to our everyday social interactions. Recent studies
      have shown that while gazing at faces, each one of us has a particular eye
      scanning pattern, highly stable across time. Although variables such as culture
      or personality have been shown to modulate gaze behavior, we still don't know
      what shapes these idiosyncrasies. Moreover, most previous observations rely on
      static analyses of small-sized eye-position data sets averaged across time. Here,
      we probe the temporal dynamics of gaze to explore what information can be
      extracted about the observers and what is being observed. Controlling for any
      stimuli effect, we demonstrate that among many individual characteristics, the
      gender of both the participant (gazer) and the person being observed (actor) are
      the factors that most influence gaze patterns during face exploration. We record
      and exploit the largest set of eye-tracking data (405 participants, 58
      nationalities) from participants watching videos of another person. Using novel
      data-mining techniques, we show that female gazers follow a much more exploratory
      scanning strategy than males. Moreover, female gazers watching female actresses
      look more at the eye on the left side. These results have strong implications in
      every field using gaze-based models from computer vision to clinical psychology.

PMID- 27893895
TI  - Corrections.

PMID- 27893896
TI  - Association Between Influenza Infection and Vaccination During Pregnancy and Risk
      of Autism Spectrum Disorder.
AB  - Importance: Maternal infections and fever during pregnancy are associated with
      increased risk for autism spectrum disorders (ASDs). To our knowledge, no study
      has investigated the association between influenza vaccination during pregnancy
      and ASD. Objective: To investigate the association between influenza infection
      and vaccination during pregnancy and ASD risk. Design, Setting, and Participants:
      This cohort study included 196 929 children born at Kaiser Permanente Northern
      California from January 1, 2000 to December 31, 2010, at a gestational age of at
      least 24 weeks. Exposures: Data on maternal influenza infection and vaccination
      from conception date to delivery date, obtained from Kaiser Permanente Northern
      California inpatient and outpatient databases. Influenza infection was defined by
      the International Classification of Diseases, Ninth Revision, Clinical
      Modification codes or positive influenza laboratory test results. Main Outcomes
      and Measures: Clinical diagnoses of ASDs identified by International
      Classification of Diseases, Ninth Revision, Clinical Modification codes 299.0,
      299.8, or 299.9 recorded in Kaiser Permanente Northern California electronic
      medical records on at least 2 occasions any time from birth through June 2015.
      Results: Within this cohort of 196 929 children, influenza was diagnosed in 1400
      (0.7%) mothers and 45 231 (23%) received an influenza vaccination during
      pregnancy. The mean (SD) ages of vaccinated and unvaccinated women were 31.6
      (5.2) and 30.4 (5.6) years, respectively. A total number of 3101 (1.6%) children
      were diagnosed with ASD. After adjusting for covariates, we found that maternal
      influenza infection (adjusted hazard ratio, 1.04; 95% CI, 0.68-1.58) or influenza
      vaccination (adjusted hazard ratio, 1.10; 95% CI, 1.00-1.21) anytime during
      pregnancy was not associated with increased ASD risk. In trimester-specific
      analyses, first-trimester influenza vaccination was the only period associated
      with increased ASD risk (adjusted hazard ratio, 1.20; 95% CI, 1.04-1.39).
      However, this association could be due to chance (P = 0.1) if Bonferroni
      corrected for the multiplicity of hypotheses tested (n = 8). Maternal influenza
      vaccination in the second or third trimester was not associated with increased
      ASD risk. Conclusions and Relevance: There was no association between maternal
      influenza infection anytime during pregnancy and increased ASD risk. There was a
      suggestion of increased ASD risk among children whose mothers received an
      influenza vaccination in their first trimester, but the association was not
      statistically significant after adjusting for multiple comparisons, indicating
      that the finding could be due to chance. These findings do not call for changes
      in vaccine policy or practice, but do suggest the need for additional studies on
      maternal influenza vaccination and autism.

PMID- 27893898
TI  - Association Between Pandemic Influenza A(H1N1) Vaccination in Pregnancy and Early
      Childhood Morbidity in Offspring.
AB  - Importance: Several studies investigating potential adverse effects of the
      pandemic A(H1N1) vaccine have supported that influenza A(H1N1) vaccination does
      not increase the risk for major pregnancy and birth adverse outcomes, but little
      is known about possible adverse effects in offspring of A(H1N1)-vaccinated
      mothers beyond the perinatal period and into early childhood. Objective: To
      evaluate whether pandemic influenza A(H1N1) vaccination in pregnancy increases
      the risk for early childhood morbidity in offspring. Design, Setting, and
      Participants: Register-based cohort study comprising all live-born singleton
      children in Denmark from pregnancies overlapping the A(H1N1) influenza
      vaccination campaign in Denmark, from November 2, 2009, to March 31, 2010. From a
      cohort of 61 359 pregnancies, offspring exposed and unexposed to the influenza
      A(H1N1) vaccine during pregnancy were matched 1:4 on propensity scores. Exposure:
      Vaccination in pregnancy with a monovalent inactivated AS03-adjuvanted split
      virion influenza A(H1N1)pdm09 vaccine (Pandemrix; GlaxoSmithKline Biologicals).
      Main Outcomes and Measures: Rate ratios of hospitalization in early childhood
      until 5 years of age. Hospitalization was defined as (1) first inpatient hospital
      admission, (2) all inpatient hospital admissions, and (3) first hospital contact
      for selected diseases, which included individual infectious diseases and
      individual neurologic, autoimmune, and behavioral conditions. Results: The mean
      (SD) age at end of follow-up was 4.6 (0.40) years for the 61 359 children
      included in the study. In the cohort, the mothers of 55 048 children were
      unvaccinated, 349 mothers were vaccinated in the first trimester, and 5962
      mothers were vaccinated in the second or third trimesters. Children exposed in
      the first trimester were not more likely to be hospitalized in early childhood
      than unexposed children (hospitalization rates per 1000 person-years, 300.6 for
      exposed vs 257.5 for unexposed; rate ratio, 1.17; 95% CI, 0.94-1.45). Similarly,
      children exposed in the second or third trimester were not more likely to be
      hospitalized in early childhood than unexposed children (hospitalization rates
      per 1000 person-years, 203.6 for exposed vs 219.3 for unexposed; rate ratio,
      0.93; 95% CI, 0.87-0.99). This 7% decreased risk was primarily a result of
      reduced risks for infectious disease-related hospitalizations. Conclusions and
      Relevance: To our knowledge, this is the most comprehensive study to date of
      potential adverse effects manifesting after the perinatal period. We detected no
      increased risk for early childhood morbidity. These results support the safety
      profile of the influenza A(H1N1) vaccine used in pregnancy.

PMID- 27893899
TI  - Incorrect Reference.

PMID- 27893900
TI  - Nursing Interventions: Need for Clarity.

PMID- 27893897
TI  - Imaging of Glial Cell Activation and White Matter Integrity in Brains of Active
      and Recently Retired National Football League Players.
AB  - Importance: Microglia, the resident immune cells of the central nervous system,
      play an important role in the brain's response to injury and neurodegenerative
      processes. It has been proposed that prolonged microglial activation occurs after
      single and repeated traumatic brain injury, possibly through sports-related
      concussive and subconcussive injuries. Limited in vivo brain imaging studies
      months to years after individuals experience a single moderate to severe
      traumatic brain injury suggest widespread persistent microglial activation, but
      there has been little study of persistent glial cell activity in brains of
      athletes with sports-related traumatic brain injury. Objective: To measure
      translocator protein 18 kDa (TSPO), a marker of activated glial cell response, in
      a cohort of National Football League (NFL) players and control participants, and
      to report measures of white matter integrity. Design, Setting, and Participants:
      This cross-sectional, case-control study included young active (n = 4) or former
      (n = 10) NFL players recruited from across the United States, and 16 age-, sex-,
      highest educational level-, and body mass index-matched control participants.
      This study was conducted at an academic research institution in Baltimore,
      Maryland, from January 29, 2015, to February 18, 2016. Main Outcomes and
      Measures: Positron emission tomography-based regional measures of TSPO using
      [11C]DPA-713, diffusion tensor imaging measures of regional white matter
      integrity, regional volumes on structural magnetic resonance imaging, and
      neuropsychological performance. Results: The mean (SD) ages of the 14 NFL
      participants and 16 control participants were 31.3 (6.1) years and 27.6 (4.9)
      years, respectively. Players reported a mean (SD) of 7.0 (6.4) years (range, 1-21
      years) since the last self-reported concussion. Using [11C]DPA-713 positron
      emission tomographic data from 12 active or former NFL players and 11 matched
      control participants, the NFL players showed higher total distribution volume in
      8 of the 12 brain regions examined (P < .004). We also observed limited change in
      white matter fractional anisotropy and mean diffusivity in 13 players compared
      with 15 control participants. In contrast, these young players did not differ
      from control participants in regional brain volumes or in neuropsychological
      performance. Conclusions and Relevance: The results suggest that localized brain
      injury and repair, indicated by higher TSPO signal and white matter changes, may
      be associated with NFL play. Further study is needed to confirm these findings
      and to determine whether TSPO signal and white matter changes in young NFL
      athletes are related to later onset of neuropsychiatric symptoms.

PMID- 27893901
TI  - The Lived Experience of Nursing Faculty in a Dedicated Education Unit.
AB  - BACKGROUND: The dedicated education unit (DEU) was developed as an innovation to
      increase enrollment capacity and secure stable clinical placement sites in units
      that provide an optimal learning environment. The purpose of this multisite study
      was to describe, interpret, and offer insight into the meanings of the lived
      experiences of nursing faculty who had transitioned to teaching in a DEU. METHOD:
      Semistructured private interviews were conducted using an interpretive
      phenomenological approach. RESULTS: The three themes that emerged were Preparing
      for, Adapting to, and Sustaining a New Synergy of Learning. Each theme had two to
      four subthemes. CONCLUSION: New DEU faculty may face decisions about physical
      presence, the nature of their interactions with staff nurse clinical instructors
      and students, and tactful approaches to managing practice issues. This study
      informs faculty how they can best prepare for success and promote sustainability.
      [J Nurs Educ. 2016;55(12):669-674.].

PMID- 27893902
TI  - A Project Team Analysis Using Tuckman's Model of Small-Group Development.
AB  - BACKGROUND: Concerns about equitable workloads for nursing faculty have been well
      documented, yet a standardized system for workload management does not exist. A
      project team was challenged to establish an academic workload management system
      when two dissimilar universities were consolidated. METHOD: Tuckman's model of
      small-group development was used as the framework for the analysis of processes
      and effectiveness of a workload project team. Agendas, notes, and meeting minutes
      were used as the primary sources of information. RESULTS: Analysis revealed the
      challenges the team encountered. Utilization of a team charter was an effective
      tool in guiding the team to become a highly productive group. Lessons learned
      from the analysis are discussed. CONCLUSION: Guiding a diverse group into a
      highly productive team is complex. The use of Tuckman's model of small-group
      development provided a systematic mechanism to review and understand group
      processes and tasks. [J Nurs Educ. 2016;55(12):675-681.].

PMID- 27893903
TI  - To Blog or Not to Blog: What Do Nursing Faculty Think?
AB  - BACKGROUND: Nurse educators find themselves tasked with developing content that
      both is aesthetically appealing and engages today's technological learners while
      empowering them to apply their knowledge in clinical and classroom settings.
      Students engaging with social networking systems reported increased satisfaction
      with collaborative peer-to-peer learning experiences, socialization, self
      reflection, peer critique, problem-solving skills, collation of evidence-based
      resources, and instructor performance. METHOD: This project included identifying
      the needs of nursing faculty regarding the use of blogging in their courses and
      barriers faced by faculty with implementing blogging in nursing curricula. A
      convenience sampling method was used, with surveys e-mailed to 49 schools of
      nursing in Illinois and 38 in Ontario. RESULTS: One hundred twenty-two surveys
      were completed: 78 in Illinois and 44 in Ontario. Results suggest there are many
      pedagogical, philosophical, and ethical issues associated with using blogging and
      technology in nursing education. CONCLUSION: Although significant challenges
      exist, blogging and technology can be useful collaborative learning tools. [J
      Nurs Educ. 2016;55(12):683-689.].

PMID- 27893904
TI  - Clinical Judgment Scripts as a Strategy to Foster Clinical Judgments.
AB  - BACKGROUND: Clinical judgment encompasses how nurses use their knowledge of the
      patient to generate, assess, and prioritize patient care alternatives. Previous
      research has identified debriefing as critical to developing clinical judgment.
      Best practice for debriefing has yet to be identified. The purpose of this
      research was to investigate whether a standard debriefing script, based on
      Tanner's clinical judgment model, could foster clinical judgment. METHOD:
      Participants were senior nursing students in their final semester of study. Data
      were gathered and analyzed from three sources: independent raters observing
      students in simulation, participating students, and the students' clinical
      instructors. RESULTS: Students identified the script as an effective debriefing
      tool, and significant improvements were observed in clinical judgment scores from
      all data sources. CONCLUSION: The standardized debriefing script helped students
      focus on the learning process, resulting in student improvement in all areas of
      clinical judgment: noticing, interpreting, responding, and reflecting. [J Nurs
      Educ. 2016;55(12):691-695.].

PMID- 27893905
TI  - Critical Care Interprofessional Education: Exploring Conflict and Power-Lessons
      Learned.
AB  - BACKGROUND: The purpose of this mixed-methods study was to evaluate the effects
      of an innovative critical care interprofessional education intervention on
      prelicensure nursing and medical students at a large public university. The class
      provided opportunities for students to (a) explore stereotypes about each
      respective profession, (b) examine the occurrence and effects of
      interprofessional conflict in high-acuity areas, and (c) explore conflict
      resolution techniques while learning how to perform critical care procedures as a
      team. METHOD: A nonequivalent control group design with pretest, posttest, and
      focus group interviews were used. RESULTS: Data analyses indicated no subscales
      and total scores were significantly different across time or between groups.
      However, focus group analyses indicated that changes did occur. CONCLUSION: The
      findings suggest that students experience interprofessional conflict in clinical
      settings, yet lack the confidence and skills to effectively mitigate these
      behaviors. Ongoing studies to measure student empowerment and their intentions to
      practice collaboratively before and after graduation are recommended. [J Nurs
      Educ. 2016;55(12):696-700.].

PMID- 27893906
TI  - Effects of a Simulation Exercise on Nursing Students' End-of-Life Care Attitudes.
AB  - BACKGROUND: Students consider end-of-life care content in their nursing curricula
      to be inadequate and deficient in promoting the development of the necessary
      attitudes to care for dying patients. Research identifies simulation as an
      effective teaching strategy to examine nursing students' attitudes toward end-of
      life care. METHOD: An end-of-life care simulation was developed, implemented, and
      evaluated. Attitudes toward caring for dying patients were measured pre- and
      postsimulation on a convenience sample of 57 sophomore nursing students using the
      Frommelt Attitudes Toward Care of the Dying Scale-Form B. Repeated measures of
      ANOVA on outcome variables evaluated student attitudes toward end-of-life care.
      RESULTS: Participation in an end-of-life care simulation resulted in more
      positive student attitudes toward caring for dying patients (p < .001).
      CONCLUSION: Simulation is an active learning strategy to incorporate end-of-life
      care in nursing curricula and improve student attitudes toward caring for dying
      patients. [J Nurs Educ. 2016;55(12):701-705.].

PMID- 27893908
TI  - Narrative Knowing: A Learning Strategy for Understanding the Role of Stories in
      Nursing Practice.
AB  - BACKGROUND: Stories are vital to understanding and creating meaning related to
      illness experiences. METHOD: An innovative learning strategy was designed and
      implemented to highlight the role of narrative and empirical ways of knowing when
      developing collaborative relationships with patients and their families. Students
      engaged in developing nursing assessments, as well as in the creative process of
      writing patient stories, to improve their understanding of human experiences of
      illness. RESULTS: Through comparing empirical and narrative data, students
      increased their awareness of different ways of knowing and the importance of
      stories to the construction of the meaning of illness. CONCLUSION: Students'
      reflective feedback indicated a shift in perception toward the inclusion of
      storied knowing within relational nursing practice. [J Nurs Educ. 2016;55(12):711
      714.].

PMID- 27893907
TI  - Patterns and Perceptions of Asynchronous Video Discussion in a Graduate Health
      Sciences Course.
AB  - BACKGROUND: Studies of graduate online education indicate a need for increased
      interaction among students and faculty. However, it can be challenging to foster
      a high level of scholarly interaction and engagement in fully online courses. The
      objective of this study was to evaluate student perceptions and participation
      patterns related to online, asynchronous video discussion in a graduate health
      sciences course. METHOD: An asynchronous video discussion was piloted in a 2014
      interprofessional informatics course and students were subsequently surveyed to
      determine their perceptions of this approach. Participation patterns were
      analyzed using descriptive statistics and social network analysis. RESULTS: The
      results indicate broad and inclusive interaction among students and faculty, with
      discussion characteristics perceived as equivalent to, or better than,
      traditional classroom discussion. The quality of student participation was high,
      and students spent additional time researching and preparing their contributions.
      CONCLUSION: This format for a seminar-style discussion holds good potential for
      effective teaching and learning in online graduate-level health courses and
      supports the development of students' critical thinking and scholarly
      communication skills. [J Nurs Educ. 2016;55(12):706-710.].

PMID- 27893909
TI  - Curricular Path to Value: Integrating an Academic Electronic Health Record.
AB  - BACKGROUND: Regulatory mandates consistently focus on quality, safety, and
      improving patient care as better evidence surfaces. One of those mandates is the
      adoption of electronic health records (EHRs) across all patient care settings.
      New graduate nurses must know how to access patient data and document and
      synthesize patient information accurately to plan safe, quality care and mitigate
      potential errors. METHOD: In an undergraduate nursing program, the objectives
      were to provide faculty with simple teaching strategies that promoted ease of
      integrating an academic EHR (AEHR) across a curriculum, as well as to steadily
      increase students' use of an AEHR. RESULTS: Faculty stressed an appreciation for
      having a supportive environment with an innovative way to educate nursing
      students. Students' feedback and course evaluations were positive, with students
      noting that they enjoyed learning in a different way. CONCLUSION: Faculty should
      continue to share their innovative teaching strategies for AEHR integration.
      Further research should include measurable outcomes of integrating an AEHR
      throughout a curriculum. [J Nurs Educ. 2016;55(12):716-719.].

PMID- 27893910
TI  - Use of Jurisprudence to Teach Professional Negligence.

PMID- 27893912
TI  - Contact Hours Versus CEUs: What's the Difference?
AB  - The terms contact hour and continuing education unit (CEU) are often used
      interchangeably. However, they are significantly different. The importance of
      correct terminology is highlighted in this article. J Contin Educ Nurs.
      2016;47(12):529-530.

PMID- 27893911
TI  - Retraining the Elephants in the Room.

PMID- 27893913
TI  - Helping Leaders Learn.
AB  - Leaders have a need to learn for individual and professional advancement. When
      leaders possess learning habits that advance to long-term recall, knowledge can
      be activated when most needed. This article presents five strategies ready for
      application to embed learning from short- to long-term memory. J Contin Educ
      Nurs. 2016;47(12):531-533.

PMID- 27893915
TI  - Barriers to Participation in an Online Nursing Journal Club at a Community
      Teaching Hospital.
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, "Barriers to Participation in an Online Nursing Journal Club at a
      Community Teaching Hospital," found on pages 536-542, 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 November 30, 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 benefits and barriers to participating in an online
      nursing journal club (ONJC) over a standard journal club. Identify three
      strategies to address the barriers to participation in an ONJC. DISCLOSURE
      STATEMENT Neither the planners nor the author have any conflicts of interest to
      disclose. BACKGROUND: Journal clubs can be an important tool enabling health care
      professionals in promoting evidence-based practice within their organizations.
      METHOD: The researchers examined 183 nurses' perceptions of an online nursing
      journal club (ONJC) and perceived barriers to participation through a survey at a
      teaching hospital. RESULTS: Time was identified as the greatest participation
      barrier. The respondents preferred journal articles regarding the topics policy
      and procedures, medications, and nursing practice changes. CONCLUSION: To
      increase the use of the ONJC, it is imperative to focus on perceived barriers and
      strategies to eliminate them to help with increasing overall participation and
      achieving success when using an ONJC. J Contin Educ Nurs. 2016;47(12):536-542.

PMID- 27893914
TI  - TeamSTEPPS in Long-Term Care-An Academic Partnership: Part II.
AB  - In 2015, the Academy for Leadership in Long-Term Care received a grant to provide
      interprofessional training on the strategies and techniques of TeamSTEPPS(r). The
      results indicated significant changes in the participants' teamwork and
      communication strategies to improve resident safety. In part two of this article,
      the discussion includes the implementation, evaluation results, and implications
      from this worthy initiative. J Contin Educ Nurs. 2016;47(12):534-535.

PMID- 27893917
TI  - Collaborative Falls Prevention: Interprofessional Team Formation, Implementation,
      and Evaluation.
AB  - As health care rapidly evolves to promote person-centered care, evidence-based
      practice, and team-structured environments, nurses must lead interprofessional
      (IP) teams to collaborate for optimal health of the populations and more cost
      effective health care. Four professions-nursing, medicine, social work, and
      pharmacy-formed a teaching team to address fall prevention among older adults in
      Oregon using an IP approach. The teaching team developed training sessions that
      included interactive, evidence-based sessions, followed by individualized team
      coaching. This article describes how the IP teaching team came together to use a
      unique cross-training approach to teach each other. They then taught and coached
      IP teams from a variety of community practice settings to foster their
      integration of team-based falls-prevention strategies into practice. After
      coaching 25 teams for a year each, the authors present the lessons learned from
      the teaching team's formation and experiences, as well as feedback from practice
      team participants that can provide direction for other IP teams. J Contin Educ
      Nurs. 2016;47(12):545-550.

PMID- 27893919
TI  - Health Literacy Competencies for Registered Nurses: An e-Delphi Study.
AB  - BACKGROUND: The Institute of Medicine's landmark report, Health Literacy: A
      Prescription to End Confusion, recommends that health professionals be trained to
      effectively communicate with patients with limited health literacy. Nurse
      specific competencies that explicitly address the needs of patients with low
      health literacy are lacking. METHOD: A national group of nurse health literacy
      experts (N = 41) participated in a three-round e-Delphi study to identify
      essential health literacy competencies for RNs in any work setting. RESULTS:
      Based on partial replication of prior work by Coleman, Hudson, and Maine, a final
      list of 50 nursing health literacy core competencies were identified in round two
      and prioritized in round three. CONCLUSION: The final list of prioritized
      competencies generated in this study have been provided as a starting point for
      health literacy education efforts in practice. J Contin Educ Nurs.
      2016;47(12):558-565.

PMID- 27893918
TI  - Breast Milk Collection and Storage in the Neonatal Intensive Care Unit: Nurses'
      Knowledge, Practice, and Perceived Barriers.
AB  - BACKGROUND: Temporary storage of human milk under appropriate conditions
      encourages prolonged breast-feeding. PURPOSE: This study aimed to assess neonatal
      nurses' knowledge and practice, as well as barriers, related to breast milk
      collection and storage and to investigate the association between nurses'
      knowledge and practice and other variables. METHOD: A cross-sectional design was
      used. Consecutive samplings of 75 nurses were recruited. The questions were based
      on a literature review of guidelines for collecting and storing breast milk from
      various sources, such as the Centers for Disease Control and Prevention and the
      Academy of Breastfeeding Medicine. RESULTS: Nurses' knowledge and practice of
      breast milk collection and storage were adequate in general, but inadequate in
      relation to issues such as discarding breast milk, the thawing process, and
      storage temperatures. Poor practices related to absence of required equipment and
      unit policy. Barriers were increased workload, inappropriate milk room (i.e., a
      small room with uncomfortable chairs and no privacy), inactive policy, and
      inadequate time. CONCLUSION: Nurses should be orientated to the guidelines and a
      unit policy to enhance evidence-based practice. J Contin Educ Nurs.
      2016;47(12):551-557.

PMID- 27893920
TI  - Perceptions of Continuing Nursing Education in Korea.
AB  - BACKGROUND: Few empirical studies examine nurses' perceptions of continuing
      nursing education and its outcomes regarding the quality of delivered service.
      This study investigated nurses' perceptions and persisting challenges with
      continuing nursing education. METHOD: Data were collected from 17 nurses with at
      least 2 years of work experience who had completed at least one continuing
      nursing education program at three university hospitals in South Korea.
      Demographic questionnaire data were collected and a prepared interview was used
      to lead focus group interaction. Phenomenological content analysis was performed
      immediately following each interview. RESULTS: Three main themes of continuing
      nursing education perceptions emerged: Feelings Toward Completing Continuing
      Nursing Education (Burden And Ambivalence); Perceptions of Completing Continuing
      Nursing Education Programs (Perceived Benefits and Problems); and Continuing
      Nursing Education-Related Educational Needs (Relevance to Practice and Reflection
      of Participants' Needs). CONCLUSION: A regionally and institutionally expanded
      study was proposed to qualitatively assess nurses' experiences on completion of
      continuing nursing education. J Contin Educ Nurs. 2016;47(12):566-572.

PMID- 27893921
TI  - Femoral Head Avascular Necrosis Is Not Caused by Arthroscopic Posterolateral
      Femoroplasty.

PMID- 27893922
TI  - Congratulations to the 2016 Blue Ribbon Article Award Winners.

PMID- 27893923
TI  - How Can We Better Educate Our Residents?

PMID- 27893924
TI  - Deciding How Best to Treat Cartilage Defects.
AB  - The decision-making regarding and treatment of cartilage abnormalities requires a
      systematic approach. This article reviews the concepts and principles that guide
      the management of this complex problem. The precise incidence, demographics, and
      progression of cartilage lesions have not been clearly delineated. Pursuing a
      patient-centered approach that considers the available nonsurgical and surgical
      options remains the cornerstone of patient care. The importance of determining
      concomitant knee pathologies, the proper interpretation and implications of
      imaging findings, and an accurate determination of the intra-articular and
      subchondral findings represent the primary elements of the decision analysis.
      Treatment options vary depending on patient goals, the disposition of the lesion,
      and a variety of other factors. The authors recommend proper patient education
      and consideration of how nonsurgical treatment or less invasive options such as
      arthroscopic debridement might be effective. If these strategies should fail,
      appropriate matching of a surgical procedure to the patient's pathology, goals,
      and expectations is warranted. Surgical options include debridement, marrow
      stimulation techniques, surface allograft treatments, autologous chondrocyte
      implantation, and osteochondral grafting (autograft and allograft) in addition to
      some emerging technologies. This article focuses on the decision-making process.
      [Orthopedics. 2016; 39(6):343-350.].

PMID- 27893926
TI  - Estimation of the optimal regime in treatment of prostate cancer recurrence from
      observational data using flexible weighting models.
AB  - Prostate cancer patients are closely followed after the initial therapy and
      salvage treatment may be prescribed to prevent or delay cancer recurrence. The
      salvage treatment decision is usually made dynamically based on the patient's
      evolving history of disease status and other time-dependent clinical covariates.
      A multi-center prostate cancer observational study has provided us data on
      longitudinal prostate specific antigen (PSA) measurements, time-varying salvage
      treatment, and cancer recurrence time. These data enable us to estimate the best
      dynamic regime of salvage treatment, while accounting for the complicated
      confounding of time-varying covariates present in the data. A Random Forest based
      method is used to model the probability of regime adherence and inverse
      probability weights are used to account for the complexity of selection bias in
      regime adherence. The optimal regime is then identified by the largest restricted
      mean survival time. We conduct simulation studies with different PSA trends to
      mimic both simple and complex regime adherence mechanisms. The proposed method
      can efficiently accommodate complex and possibly unknown adherence mechanisms,
      and it is robust to cases where the proportional hazards assumption is violated.
      We apply the method to data collected from the observational study and estimate
      the best salvage treatment regime in managing the risk of prostate cancer
      recurrence.

PMID- 27893925
TI  - A risk-based measure of time-varying prognostic discrimination for survival
      models.
AB  - Prognostic survival models are commonly evaluated in terms of both their
      calibration and their discrimination. Comparing observed and predicted survival
      curves can assess calibration, while discrimination is typically summarized
      through comparison of the properties of cases or subjects who experience an
      event, and the properties of controls represented by event-free individuals. For
      binary data, discrimination is characterized either by using the relative ranks
      of cases and controls and a receiver operating characteristic (ROC) curve, or by
      summarizing the magnitude of risk placed on cases and controls through
      calculation of the discrimination slope (DS). In this article, we propose a risk
      based measure of time-varying discrimination that generalizes the discrimination
      slope to allow use with incident events and hazard models. We refer to the new
      measure as the hazard discrimination summary (HDS) since it compares the relative
      risk among incident cases to their associated dynamic risk set controls. We
      introduce both a model-based estimation procedure that adopts the Cox model, and
      an alternative approach that locally relaxes the proportional hazards assumption.
      We illustrate the proposed methods using both a benchmark survival data set, and
      an oncology study where primary interest is in the time-varying performance of
      candidate biomarkers.

PMID- 27893927
TI  - Model averaged double robust estimation.
AB  - Researchers estimating causal effects are increasingly challenged with decisions
      on how to best control for a potentially high-dimensional set of confounders.
      Typically, a single propensity score model is chosen and used to adjust for
      confounding, while the uncertainty surrounding which covariates to include into
      the propensity score model is often ignored, and failure to include even one
      important confounder will results in bias. We propose a practical and
      generalizable approach that overcomes the limitations described above through the
      use of model averaging. We develop and evaluate this approach in the context of
      double robust estimation. More specifically, we introduce the model averaged
      double robust (MA-DR) estimators, which account for model uncertainty in both the
      propensity score and outcome model through the use of model averaging. The MA-DR
      estimators are defined as weighted averages of double robust estimators, where
      each double robust estimator corresponds to a specific choice of the outcome
      model and the propensity score model. The MA-DR estimators extend the desirable
      double robustness property by achieving consistency under the much weaker
      assumption that either the true propensity score model or the true outcome model
      be within a specified, possibly large, class of models. Using simulation studies,
      we also assessed small sample properties, and found that MA-DR estimators can
      reduce mean squared error substantially, particularly when the set of potential
      confounders is large relative to the sample size. We apply the methodology to
      estimate the average causal effect of temozolomide plus radiotherapy versus
      radiotherapy alone on one-year survival in a cohort of 1887 Medicare enrollees
      who were diagnosed with glioblastoma between June 2005 and December 2009.

PMID- 27893928
TI  - Multi-parameter regression survival modeling: An alternative to proportional
      hazards.
AB  - It is standard practice for covariates to enter a parametric model through a
      single distributional parameter of interest, for example, the scale parameter in
      many standard survival models. Indeed, the well-known proportional hazards model
      is of this kind. In this article, we discuss a more general approach whereby
      covariates enter the model through more than one distributional parameter
      simultaneously (e.g., scale and shape parameters). We refer to this practice as
      "multi-parameter regression" (MPR) modeling and explore its use in a survival
      analysis context. We find that multi-parameter regression leads to more flexible
      models which can offer greater insight into the underlying data generating
      process. To illustrate the concept, we consider the two-parameter Weibull model
      which leads to time-dependent hazard ratios, thus relaxing the typical
      proportional hazards assumption and motivating a new test of proportionality. A
      novel variable selection strategy is introduced for such multi-parameter
      regression models. It accounts for the correlation arising between the estimated
      regression coefficients in two or more linear predictors-a feature which has not
      been considered by other authors in similar settings. The methods discussed have
      been implemented in the mpr package in R.

PMID- 27893929
TI  - A review of cost communication in oncology: Patient attitude, provider
      acceptance, and outcome assessment.
AB  - The American Society of Clinical Oncology released its first guidance statement
      on the cost of cancer care in August 2009, affirming that patient-physician cost
      communication is a critical component of high-quality care. This forward-thinking
      recommendation has grown increasingly important in oncology practice today as the
      high costs of cancer care impose tremendous financial burden to patients, their
      families, and the health care system. For the current review, a literature search
      was conducted using the PubMed and Web of Science databases to identify articles
      that covered 3 topics related to patient-physician cost communication: patient
      attitude, physician acceptance, and the associated outcomes; and 15 articles from
      12 distinct studies were identified. Although most articles that addressed
      patient attitude suggested that cost communication is desired by >50% of patients
      in the respective study cohorts, only <33% of patients in those studies had
      actually discussed costs with their physicians. The literature on physician
      acceptance indicated that, although 75% of physicians considered discussions of
      out-of-pocket costs with patients their responsibility, <30% felt comfortable
      with such communication. When asked about whether cost communication actually
      took place in their practice, percentages reported by physicians varied widely
      from <10% to >60%. The data suggested that cost communication was associated with
      improved patient satisfaction, lower out-of-pocket expenses, and a higher
      likelihood of medication nonadherence; none of the studies established causality.
      Both patients and physicians expressed a strong need for accurate, accessible,
      and transparent information about the cost of cancer care. Cancer 2017;123:928
      39. (c) 2016 American Cancer Society.

PMID- 27893930
TI  - Reply to Sexual quality of life in the cancer continuum.

PMID- 27893931
TI  - Infliximab-induced tuberculosis in patients with UC: Experience from India-a
      country with high prevalence of tuberculosis.
AB  - BACKGROUND AND AIM: Tuberculosis (TB) is a well-recognized iatrogenic adverse
      event following administration of biologic therapy given for a variety of
      clinical indications. There is paucity of data on the development of TB following
      the use of biologics from countries with a high prevalence of TB. The aim of this
      study was to determine the risk of development of TB following biological therapy
      in a country, which is highly endemic for TB. METHODS: The article
      retrospectively analyse data from three referral inflammatory bowel disease
      centers to evaluate the risk of development of TB following biological therapy
      for patients with ulcerative colitis. RESULTS: Of the 79 patients with ulcerative
      colitis treated with infliximab, seven (8.8%) developed TB at a median interval
      of 8 weeks after the first exposure despite screening for latent TB. Three of the
      seven (42%) patients developed disseminated disease, whereas pulmonary disease
      was documented in four patients (57%). All patients were successfully treated
      with anti-tuberculous drugs for a period of 6-13 months. In contrast to data from
      the West, none of the patients in our study had a fatal outcome. None of the
      patients required a colectomy after a median follow up of 2 years following
      cessation of the infliximab therapy. CONCLUSIONS: These data suggest that despite
      the significantly higher prevalence, the outcome of TB after infliximab therapy
      is quite sanguine in the Indian subcontinent.

PMID- 27893932
TI  - Density-Driven Free-Convection Model for Isotopically Fractionated Geogenic
      Nitrate in Sabkha Brine.
AB  - Subsurface brines with high nitrate (NO3- ) concentration are common in desert
      environments as atmospheric nitrogen is concentrated by the evaporation of
      precipitation and little nitrogen uptake. However, in addition to having an
      elevated mean concentration of ~525 mg/L (as N), NO3- in the coastal sabkhas of
      Abu Dhabi is enriched in 15 N (mean delta15 N ~170/00), which is an enigma. A NO3
      solute mass balance analysis of the sabkha aquifer system suggests that more
      than 90% of the nitrogen is from local atmospheric deposition and the remainder
      from ascending brine. In contrast, isotopic mass balances based on Delta17 O,
      delta15 N, and delta18 O data suggest approximately 80 to 90% of the NO3- could
      be from ascending brine. As the sabkha has essentially no soil, no vegetation,
      and no anthropogenic land or water use, we propose to resolve this apparent
      contradiction with a density-driven free-convection transport model. In this
      conceptual model, the density of rain is increased by solution of surface salts,
      transporting near-surface oxygenated NO3- bearing water downward where it
      encounters reducing conditions and mixes with oxygen-free ascending geologic
      brines. In this environment, NO3- is partially reduced to nitrogen gas (N2 ),
      thus enriching the remaining NO3- in heavy isotopes. The isotopically
      fractionated NO3- and nitrogen gas return to the near-surface oxidizing
      environment on the upward displacement leg of the free-convection cycle, where
      the nitrogen gas is released to the atmosphere and new NO3- is added to the
      system from atmospheric deposition. This recharge/recycling process has operated
      over many cycles in the 8000-year history of the shallow aquifer, progressively
      concentrating and isotopically fractionating the NO3- .

PMID- 27893935
TI  - Sexual quality of life in the cancer continuum.

PMID- 27893934
TI  - Surveillance versus adjuvant radiotherapy for patients with high-risk stage I
      seminoma.
AB  - BACKGROUND: The optimal treatment strategy for patients with clinical stage I (CS
      1) seminoma is controversial. The objective of the current study was to evaluate
      the outcomes for patients considered to be at high risk of disease recurrence
      with a tumor size >=6 cm. Patients were treated with either adjuvant radiotherapy
      (RT) or followed with surveillance. METHODS: From the Danish Testicular Cancer
      database, the authors identified 473 patients with CS-1 seminoma with a tumor
      size >=6 cm. Of these, 254 patients underwent adjuvant RT and 219 were followed
      with surveillance. Cumulative incidence function was applied to estimate the risk
      of disease recurrence, risk of second malignant neoplasm, and risk of receiving
      >1 line of treatment. Survival of the 2 groups was compared with the log-rank
      test and Cox model including age at diagnosis. RESULTS: No significant
      differences were found with regard to overall survival or risk of a second
      malignant neoplasm. Patients undergoing adjuvant RT received more treatments per
      patient than patients followed with surveillance, but there was no significant
      difference noted with regard to the risk of receiving >1 line of treatment. The
      10-year cumulative incidence of disease recurrence was 32% versus 2.8%,
      respectively, for patients followed with surveillance and adjuvant RT. In
      patients followed with surveillance who developed disease recurrence, there was a
      high incidence of second recurrences after RT. CONCLUSIONS: The 10-year overall
      survival was found to be similar irrespective of primary treatment. Adjuvant RT
      was found to effectively reduce the rate of disease recurrence but resulted in
      the overtreatment of approximately two-thirds of the patients. The high incidence
      of second disease recurrences after RT in the patients followed with surveillance
      needs be addressed in future studies. Cancer 2017;123:1212-1218. (c) 2016
      American Cancer Society.

PMID- 27893933
TI  - Cancer and treatment distress psychometric evaluation over time: A BMT CTN 0902
      secondary analysis.
AB  - BACKGROUND: Routine monitoring of cancer-related distress is recognized as
      essential to quality care and mandated by a major accrediting organization.
      However, to the authors' knowledge, few cancer-specific measures have been
      developed to date to assess the multiple cancer-related factors contributing to
      this distress. In the current study, the authors examined the psychometric
      properties of the Cancer and Treatment Distress (CTXD) measure over time in
      hematopoietic cell transplantation (HCT) recipients. METHODS: As a secondary
      analysis of a multicenter randomized controlled clinical trial, adult patients
      undergoing autologous or allogeneic HCT completed patient-reported outcomes
      including the CTXD and the Medical Outcomes Study Short Form-36 (SF-36) before
      transplantation and 100 days and 180 days after HCT. RESULTS: Across 21
      transplantation centers, a total of 701 patients consented, underwent
      transplantation, and were included in the current analyses, 645 of whom were
      alive at 100 days and 618 of whom were alive at 180 days. Internal consistency
      reliability was found to be strong for the overall CTXD at the 3 time points:
      Cronbach alphas (alpha) were .94, .95, and .95, respectively. Subscale
      reliability met hypothesized levels of an alpha>.70 across time, with the lowest
      reliability noted for the Identity subscale at 180 days (alpha = .77).
      Correlations with the SF-36 Mental Health subscale were higher than with the
      Physical Functioning subscale at each time point, thereby supporting convergent
      and discriminant validity. Strong correlations of the pretransplantation CTXD
      with the posttransplantation CTXD and SF-36 Mental Health subscale supported
      predictive validity. CONCLUSIONS: The CTXD is reliable and valid as a measure of
      cancer distress both before and after HCT. It may be a useful tool for measuring
      dimensions of distress and for defining those patients requiring treatment for
      distress during and after transplantation. Cancer 2017;123:1416-1423. (c) 2016
      American Cancer Society.

PMID- 27893936
TI  - Quantifying nonadditive selection caused by indirect ecological effects: Comment.

PMID- 27893937
TI  - Prognostic significance of equivocal human epidermal growth factor receptor 2
      results and clinical utility of alternative chromosome 17 genes in patients with
      invasive breast cancer: A cohort study.
AB  - BACKGROUND: The 2013 testing guidelines for determining the human epidermal
      growth factor receptor 2 (HER2) status include new cutoff points for the
      HER2/chromosome enumeration probe 17 (CEP17) ratio and the average HER2 copy
      number per cell, and they recommend using a reflex test with alternative
      chromosome 17 probes (Ch17Ps) to resolve equivocal HER2 results. This study
      sought to determine the clinical utility of alternative Ch17Ps in equivocal cases
      and the effects of equivocal results and/or a change in the HER2 status on
      patients' outcomes. METHODS: The University of Texas MD Anderson Cancer Center
      database of HER2 dual-probe fluorescence in situ hybridization results from 2000
      to 2010 was searched for cases of invasive breast cancer with HER2/CEP17 ratios <
      2 and average HER2 copy numbers < 6 per cell. Cases with HER2 copy numbers of 4
      to < 6 (the definition of equivocal HER2 results) were analyzed with alternative
      Ch17Ps for Smith-Magenis syndrome and retinoic acid receptor alpha genes. Disease
      free survival (DFS) and overall survival (OS) were evaluated with respect to the
      HER2 copy number with multivariate Cox proportional hazards regression. RESULTS:
      Among the 3630 patients meeting the inclusion criteria, 137 (4%) had equivocal
      HER2 results. With alternative Ch17Ps, 35 of 57 equivocal HER2 cases (61%) were
      upgraded to a positive HER2 status, and 22 cases (39%) remained unchanged. The 5
      year DFS and OS adjusted hazard ratios (HRs) for copy numbers of 4 to < 6 versus
      < 4 were 0.6 (95% confidence interval [CI], 0.3-1.2) and 0.5 (95% CI, 0.2-1.0)
      with P values of .16 and .66, respectively. In comparison with HER2-negative
      cases, these CIs indicated that equivocal HER2 results were associated with
      either a protective effect (HR, < 0.5) or no effect (HR, 1.0). CONCLUSIONS: These
      findings rule out a significant deleterious effect of equivocal HER2 results.
      Alternative Ch17Ps may erroneously upgrade the HER2 status; therefore, they
      cannot be considered reliable in clinical practice. Cancer 2017;123:1115-1123.
      (c) 2016 American Cancer Society.

PMID- 27893939
TI  - Allergy UK, a national patient organisation, response to the BSACI guideline:
      prescribing an adrenaline auto-injector.

PMID- 27893938
TI  - Effect of the LIVESTRONG at the YMCA exercise program on physical activity,
      fitness, quality of life, and fatigue in cancer survivors.
AB  - BACKGROUND: Physical activity (PA) has been linked to a lower risk of developing
      and dying of cancer, yet many cancer survivors do not exercise. In the current
      study, the authors evaluated the impact of the LIVESTRONG at the YMCA exercise
      program, available at Young Men's Christian Associations (YMCAs) across the
      United States, on PA, fitness, quality of life, fatigue, body composition, serum
      biomarkers, and program safety in cancer survivors. METHODS: Cancer survivors
      were recruited through the Yale Cancer Center and the Dana-Farber Cancer
      Institute and randomized to a 12-week, twice-weekly LIVESTRONG at the YMCA
      exercise program at YMCAs in Connecticut or Massachusetts or to a control group.
      Questionnaires, dual-energy x-ray absorptiometry scans, 6-minute walk tests
      (6MWTs), and a fasting blood draw were completed at baseline and at 12 weeks.
      Intervention effects were evaluated using mixed model repeated measures analysis,
      with changes at 12 weeks in PA and 6MWT as the primary endpoints. RESULTS: A
      total of 186 participants were randomized (95 to the exercise group and 91 to the
      control group). The majority of patients were diagnosed with AJCC stage I to II
      cancer and 53% had breast cancer. Participants randomized to the LIVESTRONG at
      the YMCA program experienced increases in PA (71% exercising at >= 150
      minutes/week vs 26% of controls; P<.05) and improvements in the 6MWT (group
      difference: 28.9 meters [95% confidence interval, 0.3-49.0; P = .004]) and
      quality of life (group difference: 2.6 [95% confidence interval, 0.1-5.0; P =
      .04]). No adverse events were reported. CONCLUSIONS: The LIVESTRONG at the YMCA
      exercise program has the potential to impact thousands of survivors across the
      YMCA network and could lead to improvements in disease and psychosocial outcomes
      in the growing population of cancer survivors. Cancer 2017;123:1249-1258. (c)
      2016 American Cancer Society.

PMID- 27893940
TI  - Community healthcare professionals overestimate the risk of fatal anaphylaxis for
      food allergic children.
AB  - BACKGROUND: Fatal food anaphylaxis is rare, but a major concern for people with
      food allergy and their carers. We evaluated whether community healthcare
      professionals accurately estimate risk of fatal anaphylaxis for food allergic
      children, and whether accurate risk estimation is related to competence in
      recognizing and managing anaphylaxis. METHODS: We enrolled 90 community
      healthcare professionals in a cross-sectional survey - 30 primary care nurses, 30
      school first aiders, 30 community pharmacists. Participant risk estimates for
      fatal and non-fatal anaphylaxis, and all-cause fatalities, were measured using a
      risk ladder. Participant anaphylaxis knowledge was assessed by questionnaire, and
      practical skills using a simulated anaphylaxis scenario. RESULTS: In all three
      groups, participants significantly overestimated the risk of fatal anaphylaxis
      for food allergic children, by a mean factor of 13.5-fold (95% CI 5.0, 31.6), but
      did not overestimate non-fatal anaphylaxis risk or all-cause fatality risk. We
      found no evidence of a relationship between successful adrenaline administration
      and risk estimation. CONCLUSIONS AND CLINICAL RELEVANCE: In conclusion, we have
      found evidence that community pharmacists, school first aiders and primary care
      nurses in the UK systematically overestimate the risk of fatal anaphylaxis for a
      food allergic child. This overestimation may result in increased patient and
      carer anxiety. Community practitioners who manage childhood food allergy and
      anaphylaxis need to be educated about the level of risk for fatal anaphylaxis in
      such children.

PMID- 27893942
TI  - Response to the BSACI auto-injector guideline in Clinical & Experimental Allergy.

PMID- 27893943
TI  - Peanut allergy, anaphylaxis, adrenaline and exacerbations of asthma.

PMID- 27893945
TI  - Prescribing an adrenaline auto-injector - personalized care recommended.

PMID- 27893946
TI  - Predicting animal home-range structure and transitions using a multistate
      Ornstein-Uhlenbeck biased random walk.
AB  - The home-range concept is central in animal ecology and behavior, and numerous
      mechanistic models have been developed to understand home range formation and
      maintenance. These mechanistic models usually assume a single, contiguous home
      range. Here we describe and implement a simple home-range model that can
      accommodate multiple home-range centers, form complex shapes, allow
      discontinuities in use patterns, and infer how external and internal variables
      affect movement and use patterns. The model assumes individuals associate with
      two or more home-range centers and move among them with some estimable
      probability. Movement in and around home-range centers is governed by a two
      dimensional Ornstein-Uhlenbeck process, while transitions between centers are
      modeled as a stochastic state-switching process. We augmented this base model by
      introducing environmental and demographic covariates that modify transition
      probabilities between home-range centers and can be estimated to provide insight
      into the movement process. We demonstrate the model using telemetry data from sea
      otters (Enhydra lutris) in California. The model was fit using a Bayesian Markov
      Chain Monte Carlo method, which estimated transition probabilities, as well as
      unique Ornstein-Uhlenbeck diffusion and centralizing tendency parameters.
      Estimated parameters could then be used to simulate movement and space use that
      was virtually indistinguishable from real data. We used Deviance Information
      Criterion (DIC) scores to assess model fit and determined that both wind and
      reproductive status were predictive of transitions between home-range centers.
      Females were less likely to move between home-range centers on windy days, less
      likely to move between centers when tending pups, and much more likely to move
      between centers just after weaning a pup. These tendencies are predicted by
      theoretical movement rules but were not previously known and show that our model
      can extract meaningful behavioral insight from complex movement data.

PMID- 27893947
TI  - Challenges in the uptake of telemedicine in dentistry.
AB  - With the availability of oral care services very unevenly distributed in rural or
      remote areas, underserved people seek oral care from non-dental care providers.
      Against this backdrop, and coupled with the decreasing cost of and innovations in
      technology, there is a growing interest in the adoption of telemedicine services.
      Regardless of the lack of good-quality evidence supporting the cost-effectiveness
      of telemedicine, evidence already indicates that telemedicine, even with extra
      costs, helps in reducing the inequalities in the provision of primary health
      care. Telemedicine has the potential to overcome geographical barriers and
      contribute to closing the rural-urban healthcare gap in Australia and many other
      regions. Although research examining different teledentistry applications has
      found that this technology can be successfully integrated into different
      settings, there is little active teledentistry practice in Australia. The
      integration of telemedicine into the mainstream oral health system is a complex
      and collaborative process in which numerous factors at individual, infrastructure
      and organisational levels are involved. Addressing the barriers that delay the
      implementation of a teledentistry service can provide valuable insights into its
      lack of acceptance and establish an evidence base that can help to inform future
      decisions about the benefits of teledentistry.

PMID- 27893948
TI  - Seroprevalence and Risk Factors for Toxocara canis Infection in Serbia During
      2015.
AB  - We report data on the Toxocara seroprevalence evidenced in 2015 from samples of
      40 children and 298 adults of the population living in different areas of Serbia,
      and on possible association of certain variables with infection. Detection of
      specific antibodies was performed using an enzyme-linked immunosorbent assay; all
      ambiguous results and part of the positive and negative sera were further
      analyzed by confirmatory Western blot test. An overall 23.5% seroprevalence was
      noticed, which was confirmed in 13.0% of the examined population with no
      significant difference regarding the age (children = 10.0%; adults = 13.4%) or by
      country area (East = 18.2%; North = 15.5%, Southeastern = 9.5%; p = 0.005). In
      contrast, the group of adult women proved more reactive than men (p = 0.001), and
      subjects both who spend spare time in square/parks (p = 0.041) and with positive
      onychophagy (p = 0.001) habit turned out more exposed to the infection. Possible
      reasons of these differences were analyzed, and the medical, veterinary, and
      economic impact of this soil-transmitted zoonosis were discussed.

PMID- 27893949
TI  - Phenotypic and Genotypic Resistance of Salmonella Isolates from Healthy and
      Diseased Pigs in China During 2008-2015.
AB  - The antimicrobial resistance of Salmonella strains is rapidly increasing
      worldwide, which poses significant threats to animal and public health. In this
      study, a total of 249 porcine Salmonella isolates collected in China during 2008
      2015 were examined, including 155 clinical isolates from diseased pigs and 94
      nonclinical isolates from healthy pigs. Based on the minimum inhibitory
      concentration of seven antimicrobial agents, 96.4% of the isolates were resistant
      to at least one of the tested antibiotics and 81.0% of them showed multidrug
      resistance. The highest antimicrobial resistance was observed for tetracycline
      (85.9%), and the lowest was found for cefotaxime (13.3%). The isolates from
      diseased pigs exhibited significantly higher levels of antimicrobial resistance
      than those from healthy pigs. Twenty-two isolates from healthy pigs were
      resistant to ciprofloxacin, which may inhibit the curative effectiveness of
      fluoroquinolones on bacterial food-borne poisoning and infections in humans
      caused by contaminated food. Moreover, cefotaxime resistance of the strains
      isolated from diseased pigs during 2013-2015 was significantly higher compared
      with the strains isolated during 2008-2010. Further study showed that the
      correlation between phenotypic and genotypic resistance varied among the isolates
      from different sources, and in many cases, the presence of resistance genes was
      not consistent with the resistance to the corresponding antimicrobials. These
      results are very significant for veterinary practice and public health.

PMID- 27893950
TI  - The Relationship Between the Supply of Primary Care Physicians and Measures of
      Breast Health Service Use.
AB  - BACKGROUND: To investigate whether women are more likely to report receipt of a
      mammography recommendation from a doctor or mammography use if they reside in
      primary care service areas (PCSAs) having a greater number of clinically active
      primary care physicians. MATERIALS AND METHODS: The analysis used a nationally
      representative sample of women, aged 40 years and above (n = 10,706 unweighted
      respondents), extracted from the 2005 National Health Interview Survey. The
      restricted geocoded addresses of the respondents were linked to PCSA data on
      physician density at a secure research data center. Multivariable logistic
      regression was used to determine whether, after adjustment, specific measures of
      primary care providers (e.g., the number of obstetricians and gynecologists [Ob
      GyNs] per 10,000 population) were associated with either recommendation receipt
      or mammography use. RESULTS: After adjusting for other factors, a one-unit
      increase in the PCSA number of Ob-GyNs per 10,000 population increased the odds
      of mammography recommendation receipt by 9% and the odds of mammography use by
      9%. The ratio of international medical graduate Ob-GyNs to US-trained Ob-GyNs in
      a PCSA was negatively associated with mammography use. CONCLUSION: The results
      from this nationwide study underscore the importance of using physician density
      measures estimated from within bounded medical markets, where women reside and
      actually seek preventive breast health services. Results support the hypothesis
      that PCSA physician supply is independently associated with both mammography
      recommendation receipt and mammography utilization.

PMID- 27893951
TI  - Events Leading to Hospital-Related Disenrollment of Home Hospice Patients: A
      Study of Primary Caregivers' Perspectives.
AB  - BACKGROUND: Approximately 25% of hospice disenrollments in the United States
      occur as the result of hospitalization, which can lead to burdensome transitions
      and undesired care. Informal caregivers (e.g., spouses, children) play a critical
      role in caring for patients on home hospice. Research examining hospital-related
      disenrollment among these patients is limited. OBJECTIVE: To understand the
      events surrounding the hospitalization of patients discharged from home hospice
      through the perspective of their informal caregivers. DESIGN: Thirty-eight
      semistructured phone interviews with caregivers were conducted, and data
      regarding the events leading to hospitalization and hospice disenrollment were
      collected. Study data were analyzed by using qualitative methods.
      SETTING/SUBJECTS: Subjects included caregivers of 38 patients who received
      services from one not-for-profit home hospice organization in New York City.
      Participants were English speaking only. MEASUREMENTS: Caregiver recordings were
      transcribed and analyzed by using content analysis. RESULTS: Content analysis
      revealed four major themes contributing to hospitalization: (1)
      distressing/difficult-to-witness signs and symptoms, (2) needing palliative
      interventions not deliverable in the home setting, (3) preference to be cared for
      by nonhospice physicians or at a local hospital, and (4) caregivers not
      comfortable with the death of their care recipient at home. Over half of all
      caregivers called 911 before calling hospice. CONCLUSIONS: Our study provides
      insight into the events leading to hospitalization of home hospice patients from
      the caregivers' perspective. Further research is needed to quantify the drivers
      of hospitalization and to develop interventions that reduce utilization, while
      improving care for home hospice patients and their caregivers.

PMID- 27893953
TI  - Leveraging Telehealth to Bring Volunteer Physicians Into Underserved Communities.
AB  - Many disadvantaged communities lack sufficient numbers of local primary care and
      specialty physicians. Yet tens of thousands of physicians, in particular those
      who are retired or semiretired, desire meaningful volunteer opportunities.
      Multiple programs have begun to use telehealth to bridge the gap between
      volunteer physicians and underserved patients. In this brief, we describe
      programs that are using this model and discuss the promise and pitfalls.
      Physician volunteers in these programs report that the work can be fulfilling and
      exciting, a cutting-edge yet convenient way to remain engaged and contribute.
      Given the projected shortfall of physicians in the United States, recruiting
      retired and semiretired physicians to provide care through telehealth increases
      the total supply of active physicians and the capacity of the existing workforce.
      However, programs typically use volunteers in a limited capacity because of
      uncertainty about the level and duration of commitment. Acknowledging this
      reality, most programs only use volunteer physicians for curbside consults rather
      than fully integrating them into longitudinal patient care. The part-time
      availability of volunteers may also be difficult to incorporate into the workflow
      of busy safety net clinics. As more physicians volunteer in a growing number of
      telehealth programs, the dual benefits of enriching the professional lives of
      volunteers and improving care for underserved communities will make further
      development of these programs worthwhile.

PMID- 27893954
TI  - Does Primary Care Model Effect Healthcare at the End of Life? A Population-Based
      Retrospective Cohort Study.
AB  - BACKGROUND: Comprehensive primary care may enhance patient experience at end of
      life. OBJECTIVE: To examine whether belonging to different models of primary care
      is associated with end-of-life healthcare use and outcomes. DESIGN: Retrospective
      population cohort study, using health administrative databases to describe health
      services and costs in the last six months of life across three primary care
      models: enrolled to a physician remunerated mainly by capitation, with incentives
      for comprehensive care and access in some to allied health practitioners
      (Capitation); remunerated mainly from fee-for-service (FFS) with smaller
      incentives for comprehensive care (Enhanced FFS); and not enrolled, seeing
      physicians remunerated solely through FFS (Traditional FFS). SETTING: People who
      died from April 1, 2010 to March 31, 2013 in Ontario, Canada. MEASURES: Health
      service utilization, costs, and place of death. RESULTS: Approximately two-thirds
      (62.7%) of decedents had more contact with a specialist than family physician.
      Those in Capitation models were more likely to have the majority of physician
      services provided by a family physician (44.9% vs. 38.6% in Enhanced FFS and
      34.3% in Traditional FFS) and received more home care service days (mean 27.2 vs.
      24.2 in Enhanced FFS and 21.7 in Traditional FFS). And 22.5% had a home visit by
      a family physician. Controlling for potential confounders, decedents spent
      significantly more days in an institution in Enhanced FFS (1.1, 95% confidence
      interval [CI]: 0.9-1.5) and Traditional FFS (2.2, 95% CI: 1.8-2.6) than in
      Capitation. CONCLUSION: Decedents in comprehensive primary care models received
      more care in the community and spent less time in institutions.

PMID- 27893952
TI  - Acceptability and Impact of a Required Palliative Care Rotation with Prerotation
      and Postrotation Observed Simulated Clinical Experience during Internal Medicine
      Residency Training on Primary Palliative Communication Skills.
AB  - BACKGROUND: Improving communication training for primary palliative care using a
      required palliative care rotation for internal medicine (IM) residents has not
      been assessed. OBJECTIVE: To assess skills acquisition and acceptability for IM
      residents not selecting an elective. DESIGN: A consecutive, single-arm cohort
      underwent preobjective structured clinical examination (OSCE) with learner
      centric feedback, two weeks of clinical experience, and finally a post-OSCE to
      crystallize learner-centric take home points. SETTING/SUBJECTS: IM second year
      residents from Dartmouth-Hitchcock were exposed to a required experiential
      palliative care rotation. MEASUREMENTS: Pre- and post-OSCE using a standardized
      score card for behavioral skills, including patient-centered interviewing,
      discussing goals of care/code status, and responding to emotion, as well as a
      confidential mixed qualitative and quantitative evaluation of the experience.
      RESULTS: Twelve residents were included in the educational program (two were
      excluded because of shortened experiences) and showed statistically significant
      improvements in overall communication and more specifically in discussing code
      status and responding to emotions. General patient-centered interviewing skills
      were not significantly improved, but prerotation scores reflected pre-existing
      competency in this domain. Residents viewed the observed simulated clinical
      experience (OSCE) and required rotation as positive experiences, but wished for
      more opportunities to practice communication skills in real clinical encounters.
      CONCLUSIONS: A required palliative care experiential rotation flanked by OSCEs at
      our institution improved the acquisition of primary palliative care communication
      skills similarly to other nonclinical educational platforms, but may better meet
      the needs of the resident and faculty as well as address all required ACGME
      milestones.

PMID- 27893957
TI  - Letter from the editor.

PMID- 27893956
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 27893958
TI  - Corrigendum.

PMID- 27893959
TI  - Monoallelic Gene Expression in Mammals.
AB  - Monoallelic expression not due to cis-regulatory sequence polymorphism poses an
      intriguing problem in epigenetics because it requires the unequal treatment of
      two segments of DNA that are present in the same nucleus and that can indeed have
      absolutely identical sequences. Here, I focus on a few recent developments in the
      field of monoallelic expression that are of particular interest and raise
      interesting questions for future work. One development is regarding analyses of
      imprinted genes, in which recent work suggests the possibility that intriguing
      networks of imprinted genes exist and are important for genetic and physiological
      studies. Another issue that has been raised in recent years by a number of
      publications is the question of how skewed allelic expression should be for it to
      be designated as monoallelic expression and, further, what methods are
      appropriate or inappropriate for analyzing genomic data to examine allele
      specific expression. Perhaps the most exciting recent development in mammalian
      monoallelic expression is a clever and carefully executed analysis of genetic
      diversity of autosomal genes subject to random monoallelic expression (RMAE),
      which provides compelling evidence for distinct evolutionary forces acting on
      random monoallelically expressed genes.

PMID- 27893955
TI  - Using a Patient-Centered Outcome Measure to Test Methylphenidate Versus Placebo
      in Children with Autism Spectrum Disorder.
AB  - OBJECTIVES: Parent rating scales are commonly used to evaluate change in clinical
      trials. Despite advantages, these measures may not capture parental impression of
      the child's most salient problems. We examine the use of parent target problems
      (PTPs) in a randomized trial of methylphenidate (MPH) in children with autism
      spectrum disorder and symptoms of attention-deficit/hyperactivity disorder.
      METHODS: This multisite, 4-week, randomized crossover trial compared three dose
      levels (low, medium, and high) of MPH with placebo. At baseline, the independent
      evaluator (IE) asked parents to nominate the child's two biggest problems. For
      each problem, the IE and parent coconstructed a brief narrative of the behavior
      and the impact on family life. The IE and parents reviewed and revised the
      narratives at subsequent visits. A panel of four judges, blind to treatment
      condition, independently reviewed the narratives to rate change from baseline on
      a 9-point scale: 1, normal; 2, markedly improved; 3, definitely improved; 4,
      equivocally improved; 5, no change; 6, possibly worse; 7, definitely worse; 8,
      markedly worse; 9, disastrously worse. The mean of the four raters was compared
      with primary and key secondary ratings from the original study. RESULTS: Two PTPs
      were recorded at baseline for 60 participants. The inter-rater reliability of the
      four judges across all PTPs and time points was excellent (intraclass correlation
      = 0.95). On the primary outcome measure (Aberrant Behavior Checklist
      Hyperactivity subscale), the medium and high-dose levels were superior to
      placebo. On the mean PTP rating, only the high dose was superior to placebo. We
      also compared PTP cutoff scores 3.0 (definitely improved), 3.25, and 3.5 with the
      rate of positive response on the Improvement item of the Clinical Global
      Impressions scale in the original study. Sensitivities ranged from 68% to 88%.
      CONCLUSIONS: The parent target problem method offers a systematic way to identify
      and track patient-centered outcomes.

PMID- 27893961
TI  - The Genetics of Enteropathogenic Escherichia coli Virulence.
AB  - In many parts of the world, enteropathogenic Escherichia coli (EPEC) are a
      leading cause of death in children with diarrhea. Much of what we know about the
      pathogenesis of EPEC infections is based on the study of one or two prototypic
      strains that have provided deep insight into the precise mechanisms by which EPEC
      colonizes the intestine, evades host immunity, and spreads from person to person.
      In some cases, defining the biochemical activity of the host-interacting effector
      proteins from these prototypic strains has led to the discovery of novel post
      translational protein modifications and new understandings of biology and host
      pathogen interactions. However, genomic analysis of recent EPEC isolates has
      revealed that the EPEC pathotype is more diverse than previously appreciated.
      Although by definition all strains carry the locus of enterocyte effacement, the
      effector repertoires of different clonal groups are quite divergent, suggesting
      that there is still a great deal to learn about the genetic basis of EPEC
      virulence.

PMID- 27893962
TI  - Proteopathic Strains and the Heterogeneity of Neurodegenerative Diseases.
AB  - Most age-related neurodegenerative diseases are associated with the misfolding
      and aberrant accumulation of specific proteins in the nervous system. The
      proteins self-assemble and spread by a prion-like process of corruptive molecular
      templating, whereby abnormally folded proteins induce the misfolding and
      aggregation of like proteins into characteristic lesions. Despite the apparent
      simplicity of this process at the molecular level, diseases such as Alzheimer's,
      Parkinson's, Creutzfeldt-Jakob, and others display remarkable phenotypic
      heterogeneity, both clinically and pathologically. Evidence is growing that this
      variability is mediated, at least in part, by the acquisition of diverse
      molecular architectures by the misfolded proteins, variants referred to as
      proteopathic strains. The structural and functional diversity of the assemblies
      is influenced by genetic, epigenetic, and local contextual factors. Insights into
      proteopathic strains gleaned from the classical prion diseases can be profitably
      incorporated into research on other neurodegenerative diseases. Their potentially
      wide-ranging influence on disease phenotype also suggests that proteopathic
      strains should be considered in the design and interpretation of diagnostic and
      therapeutic approaches to these disorders.

PMID- 27893960
TI  - Eukaryotic DNA Polymerases in Homologous Recombination.
AB  - Homologous recombination (HR) is a central process to ensure genomic stability in
      somatic cells and during meiosis. HR-associated DNA synthesis determines in large
      part the fidelity of the process. A number of recent studies have demonstrated
      that DNA synthesis during HR is conservative, less processive, and more mutagenic
      than replicative DNA synthesis. In this review, we describe mechanistic features
      of DNA synthesis during different types of HR-mediated DNA repair, including
      synthesis-dependent strand annealing, break-induced replication, and meiotic
      recombination. We highlight recent findings from diverse eukaryotic organisms,
      including humans, that suggest both replicative and translesion DNA polymerases
      are involved in HR-associated DNA synthesis. Our focus is to integrate the
      emerging literature about DNA polymerase involvement during HR with the unique
      aspects of these repair mechanisms, including mutagenesis and template switching.

PMID- 27893963
TI  - Regulated Proteolysis in Bacteria: Caulobacter.
AB  - Protein degradation is essential for all living things. Bacteria use energy
      dependent proteases to control protein destruction in a highly specific manner.
      Recognition of substrates is determined by the inherent specificity of the
      proteases and through adaptor proteins that alter the spectrum of substrates. In
      the alpha-proteobacterium Caulobacter crescentus, regulated protein degradation
      is required for stress responses, developmental transitions, and cell cycle
      progression. In this review, we describe recent progress in our understanding of
      the regulated and stress-responsive protein degradation pathways in Caulobacter.
      We discuss how organization of highly specific adaptors into functional
      hierarchies drives destruction of proteins during the bacterial cell cycle.
      Because all cells must balance the need for degradation of many true substrates
      with the toxic consequences of nonspecific protein destruction, principles found
      in one system likely generalize to others.

PMID- 27893967
TI  - Does Orthodontic Extraction Treatment Improve the Angular Position of Third
      Molars? A Systematic Review.
AB  - PURPOSE: To systematically assess the available evidence on the effect of
      orthodontic extractions on third molar (M3) angulation. MATERIALS AND METHODS:
      Three databases were searched up to April 25, 2016 to identify orthodontic
      studies comparing M3 angular changes in patients with and without extraction.
      Information on methodology, treatment procedures, and outcome was retrieved from
      each study. Assessment of overall and individual quality of the included studies
      was performed using validated criteria. RESULTS: Fourteen retrospective studies
      were considered eligible for this systematic review. Two studies achieved a
      moderate evidence score, whereas the lowest grade was assigned to 12 studies. The
      overall evidence level was classified as limited. Meta-analysis was not feasible
      because of the high heterogeneity across studies. Based on the best available
      evidence, premolar extraction followed by fixed orthodontic appliances can
      substantially improve the angular position of M3s by 10 degrees  to 18 degrees .
      CONCLUSIONS: There is limited evidence that orthodontic extractions can
      substantially enhance the uprighting of M3s. Clinicians should be aware of the
      potentially beneficial effect of orthodontic extraction treatment on M3
      development, although well-designed prospective studies are necessary to
      strengthen this statement.

PMID- 27893968
TI  - Interprofessional approach for teaching functional knee joint anatomy.
AB  - Profound knowledge in functional and clinical anatomy is a prerequisite for
      efficient diagnosis in medical practice. However, anatomy teaching does not
      always consider functional and clinical aspects. Here we introduce a new
      interprofessional approach to effectively teach the anatomy of the knee joint.
      The presented teaching approach involves anatomists, orthopaedists and physical
      therapists to teach anatomy of the knee joint in small groups under functional
      and clinical aspects. The knee joint courses were implemented during early stages
      of the medical curriculum and medical students were grouped with students of
      physical therapy to sensitize students to the importance of interprofessional
      work. Evaluation results clearly demonstrate that medical students and physical
      therapy students appreciated this teaching approach. First evaluations of
      following curricular anatomy exams suggest a benefit of course participants in
      knee-related multiple choice questions. Together, the interprofessional approach
      presented here proves to be a suitable approach to teach functional and clinical
      anatomy of the knee joint and further trains interprofessional work between
      prospective physicians and physical therapists as a basis for successful
      healthcare management.

PMID- 27893972
TI  - Audio Summary.

PMID- 27893966
TI  - Vaccination via Chloroplast Genetics: Affordable Protein Drugs for the Prevention
      and Treatment of Inherited or Infectious Human Diseases.
AB  - Plastid-made biopharmaceuticals treat major metabolic or genetic disorders,
      including Alzheimer's, diabetes, hypertension, hemophilia, and retinopathy.
      Booster vaccines made in chloroplasts prevent global infectious diseases, such as
      tuberculosis, malaria, cholera, and polio, and biological threats, such as
      anthrax and plague. Recent advances in this field include commercial-scale
      production of human therapeutic proteins in FDA-approved cGMP facilities,
      development of tags to deliver protein drugs to targeted human cells or tissues,
      methods to deliver precise doses, and long-term stability of protein drugs at
      ambient temperature, maintaining their efficacy. Codon optimization utilizing
      valuable information from sequenced chloroplast genomes enhanced expression of
      eukaryotic human or viral genes in chloroplasts and offered unique insights into
      translation in chloroplasts. Support from major biopharmaceutical companies,
      development of hydroponic production systems, and evaluation by regulatory
      agencies, including the CDC, FDA, and USDA, augur well for advancing this novel
      concept to the clinic and revolutionizing affordable healthcare.

PMID- 27893964
TI  - Aneuploidy in Cancer and Aging.
AB  - Chromosomal instability (CIN), the persistent inability of a cell to faithfully
      segregate its genome, is a feature of many cancer cells. It stands to reason that
      CIN enables the acquisition of multiple cancer hallmarks; however, there is a
      growing body of evidence suggesting that CIN impairs cellular fitness and
      prevents neoplastic transformation. Here, we suggest a new perspective to
      reconcile this apparent paradox and share an unexpected link between aneuploidy
      and aging that was discovered through attempts to investigate the CIN-cancer
      relationship. Additionally, we provide a comprehensive overview of the function
      and regulation of the anaphase-promoting complex, an E3 ubiquitin ligase that
      mediates high-fidelity chromosome segregation, and describe the mechanisms that
      lead to whole-chromosome gain or loss. With this review, we aim to expand our
      understanding of the role of CIN in cancer and aging with the long-term objective
      of harnessing this information for the advancement of patient care.

PMID- 27893969
TI  - Hospital characteristics and favourable neurological outcome among patients with
      out-of-hospital cardiac arrest in Osaka, Japan.
AB  - OBJECTIVE: To assess the association between favourable neurological outcome and
      hospital characteristics such as hospital volume and number of critical care
      centres (CCMCs) after out-of-hospital cardiac arrest (OHCA). METHODS: This
      retrospective, population-based observational study conducted in Osaka
      Prefecture, Japan included adult patients with OHCA, aged >=18 years who were
      transported to acute care hospitals between January 2005 and December 2012. We
      divided acute care hospitals into CCMCs or non-CCMCs, the latter of which were
      divided into the following three groups according to the annual average number of
      transported OHCA cases: low-volume (<=10 cases), middle-volume (11-39 cases), and
      high-volume (>=40 cases) groups. Random effects logistic regression models, with
      hospital treated as a random effect, were used to assess factors potentially
      associated with a favourable neurological outcome. RESULTS: A total of 44,474
      patients were eligible. The proportions of favourable neurological outcome from
      OHCA were 0.9% (31/3559) in the low-volume group, 1.2% (106/9171) in the middle
      volume group, 1.6% (222/14,007) in the high-volume group, and 4.3% (766/17,737)
      in the CCMC group (P<0.001). In the multivariable analysis, transport to CCMCs
      was significantly associated with favourable neurological outcome, compared with
      transport to non-CCMCs (adjusted odds ratio 1.63; 95% confidence interval, 1.60
      1.66). Among the non-CCMC group, there was no significant relationship between
      hospital volume and favourable neurological outcome. CONCLUSIONS: In this
      population, transport of OHCA patients to CCMCs led to significantly higher one
      month survival rates with favourable neurological outcome from OHCA, whereas no
      significant association was noted among the hospitals with different volumes.

PMID- 27893965
TI  - Single-Cell and Single-Molecule Analysis of Gene Expression Regulation.
AB  - Recent advancements in single-cell and single-molecule imaging technologies have
      resolved biological processes in time and space that are fundamental to
      understanding the regulation of gene expression. Observations of single-molecule
      events in their cellular context have revealed highly dynamic aspects of
      transcriptional and post-transcriptional control in eukaryotic cells. This
      approach can relate transcription with mRNA abundance and lifetimes. Another key
      aspect of single-cell analysis is the cell-to-cell variability among populations
      of cells. Definition of heterogeneity has revealed stochastic processes,
      determined characteristics of under-represented cell types or transitional
      states, and integrated cellular behaviors in the context of multicellular
      organisms. In this review, we discuss novel aspects of gene expression of
      eukaryotic cells and multicellular organisms revealed by the latest advances in
      single-cell and single-molecule imaging technology.

PMID- 27893973
TI  - Progressive Dysphagia in a Pregnant Woman.

PMID- 27893974
TI  - A Surprising Case of Acute Diarrhea in the South of France.

PMID- 27893975
TI  - Gingival Carcinoma in a Patient With Ulcerative Colitis?

PMID- 27893976
TI  - Reply.

PMID- 27893977
TI  - Reply.

PMID- 27893979
TI  - No Excess Cancer Recurrence After Immunosuppressive Drugs in a Meta-analysis of
      Cohorts of Patients With Immune-mediated Diseases: A Mirage Related to Propensity
      Bias?

PMID- 27893980
TI  - Managing Crohn's Disease After Surgery: A Patient Guide.

PMID- 27893978
TI  - Unusual Thickened Gastric Folds in a Patient With Breast Cancer.

PMID- 27893982
TI  - Reply.

PMID- 27893981
TI  - An Unusual Rash During Evaluation for Chronic Pancreatitis.

PMID- 27893983
TI  - A Rare Submucosal Tumor of the Esophagus.

PMID- 27893984
TI  - Indomethacin to Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis:
      When and How?

PMID- 27893985
TI  - Unusual Colonic Obstruction.

PMID- 27893986
TI  - A formative evaluation of the recovery public works programme in Blantyre City,
      Malawi.
AB  - Public works programmes (PWPs) are popular social protection instruments in the
      context of chronic poverty but very little has been published in the way of
      implementation and outcomes of these programmes. This paper presents a formative
      process and outcome evaluation of the recovery PWP in Blantyre City, Malawi. The
      evaluation used longitudinal household survey data of PWP beneficiaries,
      programme records and interview responses from programme staff and community
      leaders. Largely, the process evaluation findings showed an agreement between
      actual and planned activities. The outcome evaluation found indications that the
      PWP community assets offered some potential benefits to the communities, and that
      PWP wages allowed the beneficiaries to purchase some food. This however, did not
      translate into more meals per day, nor did the earnings prevent the decline in
      household assets as expected. Given a plausible PWP theory and high
      implementation fidelity, the PWP wage rate or number of days was either just
      enough to smooth participant income, or insufficient altogether, to enable
      achievement of more distal outcomes.

PMID- 27893988
TI  - WITHDRAWN: Endothelin signaling in bone.

PMID- 27893989
TI  - Drug discovery targeting heme-based sensors and their coupled activities.
AB  - Heme-based sensors have emerged during the last 20years as being a large family
      of proteins that occur in all kingdoms of life. A myriad of biological
      adaptations are associated with these sensors, which include vasodilation,
      bacterial virulence, dormancy, chemotaxis, biofilm formation, among others. Due
      to the key activities regulated by these proteins along with many other systems
      that use similar output domains, there is a growing interest in developing small
      molecules as their regulators. Here, we review the development of potential
      activators and inhibitors for many of these systems, including human soluble
      guanylate cyclase, c-di-GMP-related enzymes, Mycobacterium tuberculosis
      DevR/DevS/DosT (differentially expressed in virulent strain response
      regulator/sensor/dormancysurvival sensorT), the Rev-erb-alpha and beta nuclear
      receptor, among others. The possible roles of these molecules as biochemical
      tools, therapeutic agents, and novel antibiotics are critically examined.

PMID- 27893987
TI  - Transdisciplinary approaches enhance the production of translational knowledge.
AB  - The primary goal of translational research is to generate and apply knowledge
      that can improve human health. Although research conducted within the confines of
      a single discipline has helped us to achieve this goal in many settings, this
      unidisciplinary approach may not be optimal when disease causation is complex and
      health decisions are pressing. To address these issues, we suggest that
      transdisciplinary approaches can facilitate the progress of translational
      research, and we review publications that demonstrate what these approaches can
      look like. These examples serve to (1) demonstrate why transdisciplinary research
      is useful, and (2) stimulate a conversation about how it can be further promoted.
      While we note that open-minded communication is a prerequisite for germinating
      any transdisciplinary work and that epidemiologists can play a key role in
      promoting it, we do not propose a rigid protocol for conducting transdisciplinary
      research, as one really does not exist. These achievements were developed in
      settings where typical disciplinary and institutional barriers were surmountable,
      but they were not accomplished with a single predetermined plan. The benefits of
      cross-disciplinary communication are hard to predict a priori and a detailed
      research protocol or process may impede the realization of novel and important
      insights. Overall, these examples demonstrate that enhanced cross-disciplinary
      information exchange can serve as a starting point that helps researchers frame
      better questions, integrate more relevant evidence, and advance translational
      knowledge more effectively. Specifically, we discuss examples where
      transdisciplinary approaches are helping us to better explore, assess, and
      intervene to improve human health.

PMID- 27893990
TI  - Ferrocenyl naphthalene diimides as tetraplex DNA binders.
AB  - Seven ferrocenyl naphthalene diimide (FND) ligands were synthesized. Each had a
      higher affinity for tetraplex DNA than for either single- or double-stranded DNA.
      The FND binding affinities were >105M-1 in 0.10M AcOH-AcONa or AcOH-AcOK (pH5.5)
      containing 0.10M NaCl or KCl. The FNDs with the highest binding affinities for
      tetraplex DNA showed 23- or 8-times higher preference for tetraplex DNA than for
      single- or double-stranded DNA, respectively. The current signals generated from
      the seven FNDs bound to the tetraplex DNA immobilized on the electrode were found
      to correlate with the binding affinities of these ligands for the tetraplex DNA.
      Furthermore, using the telomerase repeat amplification protocol assay, the FND
      ligands could be categorized into three groups: (a) inhibiting both telomerase
      and Taq polymerase, (b) inhibiting telomerase alone, and (c) inhibiting neither
      telomerase nor Taq polymerase.

PMID- 27893991
TI  - SacLab: A toolbox for saccade analysis to increase usability of eye tracking
      systems in clinical ophthalmology practice.
AB  - PURPOSE: Many open source software packages have been recently developed to
      expand the usability of eye tracking systems to study oculomotor behavior, but
      none of these is specifically designed to encompass all the main functions
      required for creating eye tracking tests and for providing the automatic analysis
      of saccadic eye movements. The aim of this study is to introduce SacLab, an
      intuitive, freely-available MATLAB toolbox based on Graphical User Interfaces
      (GUIs) that we have developed to increase the usability of the ViewPoint
      EyeTracker (Arrington Research, Scottsdale, AZ, USA) in clinical ophthalmology
      practice. METHODS: SacLab consists of four processing modules that enable the
      user to easily create visual stimuli tests (Test Designer), record saccadic eye
      movements (Data Recorder), analyze the recorded data to automatically extract
      saccadic parameters of clinical interest (Data Analyzer) and provide an aggregate
      analysis from multiple eye movements recordings (Saccade Analyzer), without
      requiring any programming effort by the user. RESULTS: A demo application of
      SacLab to carry out eye tracking tests for the analysis of horizontal saccades
      was reported. We tested the usability of SacLab toolbox with three
      ophthalmologists who had no programming experience; the ophthalmologists were
      briefly trained in the use of SacLab GUIs and were asked to perform the demo
      application. The toolbox gained an enthusiastic feedback from all the clinicians
      in terms of intuitiveness, ease of use and flexibility. Test creation and data
      processing were accomplished in 52+/-21s and 46+/-19s, respectively, using the
      SacLab GUIs. CONCLUSIONS: SacLab may represent a useful tool to ease the
      application of the ViewPoint EyeTracker system in clinical routine in
      ophthalmology.

PMID- 27893992
TI  - Prediction of myocardial infarction by assessing regional cardiac wall in CMR
      images through active mesh modeling.
AB  - Myocardial infarction is a leading cause of morbidity and mortality. In this
      study, using Cine MRI images, the infarct region was precisely determined by
      examining the local migration path length of critical points on myocardium
      borders and the fractional thickening effects. First, MRI Cine images of
      Epi/Endocardium were processed in 3D for all slices, and then incorporated in all
      frames to build a dynamic model. Epi/Endocardium images were segmented using
      Heiberg algorithm, and then by a robust restricted block matching algorithm, the
      sparse points were tracked. Finally, by fitting a 3D active mesh model to the
      sparse point displacements, a dense motion field was obtained, and some useful
      local parameters of left ventricle in patients with myocardial infarction were
      estimated. The local parameters are path length, fractional thickening, and
      strain. Using this process, the cardiac wall motion was quantized to determine
      the region and extent of infarct lesion. The process was implemented, and the
      results were examined and modified against the cardiac perfusion scan. Data were
      acquired from 10 healthy individuals and 20 patients with the myocardial
      infarction. The findings also reveal that the infarct region can be determined by
      locating less than 20% in the wall thickening. In all the patients, the process
      was able to precisely determine the affected region. The cardiac wall kinesis in
      damaged regions was properly evaluated by normalized path length and presented in
      standard bull's-eye format. The above approach is promising and can be extended
      in prognosis of acute heart infraction by prediction of prone to the wall kinesis
      regions in the patients close to MI by examining the local indexes of the
      myocardium in the cardiac MRI images.

PMID- 27893993
TI  - Mediated effects of perceived discrimination on adolescent academic achievement:
      A test of four models.
AB  - Many adolescents feel they are subjected to acts of discrimination. Research
      shows that discrimination is associated with adverse outcomes including poor
      psychological adjustment, school adjustment, and academic achievement. This study
      investigated alternative pathways through which discrimination affects
      adolescents' academic achievement. A sample of 244 Year 7-10 Australian secondary
      school students (65% male; Mage = 13.6 years; SD = 1.24) completed questionnaires
      measuring discrimination, psychological adjustment, and sense of school
      membership. Both at the time of questionnaire completion and one semester later,
      absenteeism data, teacher ratings of classroom behavior, and academic grades were
      retrieved from school records. The fit of four competing structural models were
      compared. In the best fitting model, the effects of prior discrimination on
      academic achievement one semester later were serially mediated, first through
      psychological adjustment, and then through school adjustment. By elucidating
      these mechanisms, the study informs theory and practice regarding the effects of
      discrimination on adolescents.

PMID- 27893994
TI  - Shortening Scarf osteotomy for correction of severe hallux valgus. Does
      shortening affect the outcome?
AB  - BACKGROUND: Translation and shortening of Scarf osteotomy allows correction of
      severe hallux valgus deformity. Shortening may result in transfer metatarsalgia.
      AIM: To evaluate outcome of patients undergoing shortening Scarf osteotomy for
      severe hallux valgus deformities. MATERIALS AND METHODS: Fifteen patients
      (20feet, mean age 58 years) underwent shortening Scarf osteotomy for severe
      hallux valgus deformities. Outcomes were pre and postoperative AOFAS scores, IM
      and HV angles, patient satisfaction. RESULTS: Mean follow-up was 25 months (range
      22-30). The IM angle improved from a median of 18.60 (range 13.4-26.20)
      preoperatively to 9.70 (range 8.0-13.70) postoperatively (8.9; 95% CI=7.6-10.3;
      p<0.001). The HV angle improved from a mean of 43.2 (range 27.4-68.2)
      preoperatively to 13.6 (range 3.0-37.4) postoperatively (29.6; 95% CI=26.1-33.2;
      p<0.001). The median AOFAS score improved from 29.2 (range 14-60) preoperatively
      to 82.2 (range 55-100) postoperatively (53.0; 95% CI=48.0-58.5; p<0.001). All
      patients rated their satisfaction as either satisfied or very satisfied. None had
      symptoms of transfer metatarsalgia at final follow-up. All osteotomies united.
      CONCLUSIONS: Shortening Scarf osteotomy is a viable option for treating severe
      hallux valgus deformities with no transfer metatarsalgia.

PMID- 27893996
TI  - Frequency and pattern of Internet use in patients with schizophrenia or bipolar
      disorders seeking medical information.
AB  - The aim was to explore how patients with bipolar (N=59) or psychotic disorder
      (N=41) seek medical information on Internet (e-patient). Two-thirds (64%) of
      inpatients interviewed using a standardized semi-structured questionnaire were e
      patients. Compared to non e-patients, they were younger and had a higher
      educational level. The proportion of e-patients was comparable among persons with
      schizophrenia (61%) and with bipolar disorder (66%). Very few patients were
      familiar with quality codes for Internet medical information. Patients should be
      informed about how to recognize reliable information on the Internet and web
      sites should cater for their cognitive deficits.

PMID- 27893995
TI  - Combined effects of cadmium, temperature and hypoxia-reoxygenation on
      mitochondrial function in rainbow trout (Oncorhynchus mykiss).
AB  - Although aquatic organisms face multiple environmental stressors that may
      interact to alter adverse outcomes, our knowledge of stressor-stressor
      interaction on cellular function is limited. We investigated the combined effects
      of cadmium (Cd), hypoxia-reoxygenation (H-R) and temperature on mitochondrial
      function. Liver mitochondria from juvenile rainbow trout were exposed to Cd (0
      20MUM) and H-R (0 and 5min) at 5, 13 and 25 degrees C followed by measurements of
      mitochondrial Cd load, volume, complex I active (A)<->deactive (D) transition,
      membrane potential, ROS release and ultrastructural changes. At high temperature
      Cd exacerbated H-R-imposed reduction of maximal complex I (CI) respiration
      whereas at low temperature 5 and 10MUM stimulated maximal CI respiration post H
      R. The basal respiration showed a biphasic response at high temperatures with low
      Cd concentrations reducing the stimulatory effect of H-R and high concentrations
      enhancing this effect. At low temperature Cd monotonically enhanced H-R-induced
      stimulation of basal respiration. Cd and H-R reduced both the P/O ratio and the
      RCR at all 3 temperatures. Temperature rise alone increased mitochondrial Cd load
      and toxicity, but combined H-R and temperature exposure reduced mitochondrial Cd
      load but surprisingly exacerbated the mitochondrial dysfunction. Mitochondrial
      dysfunction induced by H-R was associated with swelling of the organelle and
      blocking of conversion of CI D to A form. However, low amounts of Cd protected
      against H-R induced swelling and prevented the inhibition of H-R-induced CI D to
      A transition. Both H-R and Cd dissipated mitochondrial membrane potential
      Deltapsim and damaged mitochondrial structure. We observed increased reactive
      oxygen species (H2O2) release that together with the protection afforded by EGTA,
      vitamin E and N-acetylcysteine against the Deltapsim dissipation suggested direct
      involvement of Cd and oxidative stress. Overall, our findings indicate that
      mitochondrial sensitivity to Cd toxicity was enhanced by the effects of H-R and
      temperature, and changes in mitochondrial Cd load did not always explain this
      effect.

PMID- 27893997
TI  - Psychometric properties of dual-task balance and walking assessments for
      individuals with neurological conditions: A systematic review.
AB  - BACKGROUND: The ability of performing a balance or walking task in conjunction
      with a secondary cognitive or motor task, referred to as dual-task (DT) ability,
      is essential in daily living. While there is some evidence that DT performance is
      impaired in individuals with neurological conditions, using reliable and valid
      tools to measure DT performance is essential. This systematic review aimed to
      evaluate the psychometric properties of DT balance and walking assessments in
      individuals with different neurological conditions. METHODS: A systematic
      literature search was conducted using PubMed, CINAHL, MEDLINE, PsycINFO, SCOPUS,
      Web of Science, and Cochrane Library (last search done in April 2016). The
      methodological quality was rated using the Consensus-based Standards for the
      selection of health Measurement Instruments (COSMIN) checklist. RESULTS: Twenty
      three articles involving individuals with stroke, Parkinson's disease, mild
      cognitive impairment, dementia, Alzheimer's disease, and multiple sclerosis were
      included. Outcomes derived from the walking tasks under DT condition generally
      demonstrated good reliability (correlation coefficient >=0.75) across different
      neurological disorders, but their usefulness in distinguishing fallers from non
      fallers was inconclusive. The reliability of outcomes derived from the
      cognitive/motor tasks and from the dual-task effect (DTE) (i.e., DT performance
      minus single-task performance) seemed to be lower but was understudied. The
      reliability of static or dynamic sitting/standing balance outcomes in DT
      condition was not assessed in any of the selected studies. CONCLUSIONS: The
      reliability of the outcomes derived from walking tasks was good. The psychometric
      properties of other DT outcomes need to be further investigated.

PMID- 27893998
TI  - Influenza and rhinovirus viral load and disease severity in upper respiratory
      tract infections.
AB  - BACKGROUND: The role of viral load in respiratory viral infection is unclear. It
      is proposed that the viral load of some, but not all respiratory viruses
      correlate with disease severity. OBJECTIVES: We aimed to determine if an
      association exists between viral loads among patients in ambulatory settings,
      compared to those requiring hospitalization/intensive care unit (ICU) admission
      with influenza A/H3N2, influenza B, or human rhinovirus (HRV); we also explored
      the impact of age, gender and co-detection of Streptococcus pneumoniae on patient
      setting. We hypothesized that hospitalized/ICU patients have higher respiratory
      virus viral loads compared to ambulatory (e.g. walk-in clinics, family
      practices)/ER patients. STUDY DESIGN: We quantified viral load by in-house real
      time RT-PCR in 774 nasopharyngeal swabs with influenza A/H3N2, or B or HRV
      viruses from various patient settings in Ontario, Canada. RESULTS: Mean viral
      load (log10 copies/ml) of influenza A/H3N2 (6.94) was higher than influenza B
      (4.96) and HRV (5.58) (p<0.0001). Influenza A/H3N2 viral loads were highest in
      infants and the elderly; however, increased A/H3N2 viral loads were not
      associated with hospitalization/ICU admission compared to swabs collected in
      ambulatory/ER settings. Influenza B viral loads were higher in patients in
      hospital/ICU settings compared to those in ambulatory settings (OR 1.28, 95% CI
      1.11-1.47). HRV viral loads did not differ by age (p=0.67) or setting (p=0.54);
      there was no association between S. pneumoniae colonization and setting for any
      virus. CONCLUSION: When compared to ambulatory/ER patients, viral load was higher
      in hospitalized/ICU patients with influenza B, but not influenza A or HRV.

PMID- 27893999
TI  - Ebola virus disease: An update on current prevention and management strategies.
AB  - Ebola virus disease (EVD) is characterised by systemic viral replication, immuno
      suppression, abnormal inflammatory responses, large volume fluid and electrolyte
      losses, and high mortality in under-resourced settings. There are various
      therapeutic strategies targeting EVD including vaccines utilizing different
      antigen delivery methods, antibody-based therapies and antiviral drugs. These
      therapies remain experimental, but received attention following their use
      particularly in cases treated outside West Africa during the 2014-15 outbreak, in
      which 20 (80%) out of 25 patients survived. Emerging data from current trials
      look promising and are undergoing further study, however optimised supportive
      care remains the key to reducing mortality from EVD.

PMID- 27894000
TI  - Synthesis and fluorescence studies of nine 1,5-benzodiazepine-2,4-dione
      derivatives: Dual emission and excimer fluorescence.
AB  - The photophysical properties of nine 1,5-benzodiazepine-2,4-dione (BZD)
      derivatives were investigated using absorption and fluorescence spectral
      techniques in dimethyl sulfoxide. The trend of red shifts caused by the
      substitutions had full compliance with the trend of decreasing the calculated
      band gap (DeltaELUMO-HOMO) by semi-empirical AM1 and DFT/B3LYP/6-311+G*
      computational methods. The positive solvatochromism of BZD a demonstrated the pi
      pi* nature of the singlet excited state. Dual fluorescence was observed in the
      emission spectra of BZD f and g, while their spectrum in different concentration
      showed only one peak short wavelength (SW) in dilute solutions. The main peak in
      SW around 370nm was attributed to the monomer of BZD (f* or g*) and the broader
      emission shifted to the visible region around 400nm in middle wavelength (MW) to
      the intermolecular excimer emission of BZD ([f/f]*or [g/g]*). The observed
      phenomena, such as solvatochromism, dual fluorescence, some red shifts caused by
      substitution, and larger Stokes shift indicated the existence of intramolecular
      charge transfer (ICT) in the BZDs series. The phosphorescence emission of the
      BZDs demonstrated their intersystem crossing (ISC) process.

PMID- 27894001
TI  - Multiresolution eXtended Free-Form Deformations (XFFD) for non-rigid registration
      with discontinuous transforms.
AB  - Image registration is an essential technique to obtain point correspondences
      between anatomical structures from different images. Conventional non-rigid
      registration methods assume a continuous and smooth deformation field throughout
      the image. However, the deformation field at the interface of different organs is
      not necessarily continuous, since the organs may slide over or separate from each
      other. Therefore, imposing continuity and smoothness ubiquitously would lead to
      artifacts and increased errors near the discontinuity interface. In computational
      mechanics, the eXtended Finite Element Method (XFEM) was introduced to handle
      discontinuities without using computational meshes that conform to the
      discontinuity geometry. Instead, the interpolation bases themselves were enriched
      with discontinuous functional terms. Borrowing this concept, we propose a
      multiresolution eXtented Free-Form Deformation (XFFD) framework that seamlessly
      integrates within and extends the standard Free-Form Deformation (FFD) approach.
      Discontinuities are incorporated by enriching the B-spline basis functions
      coupled with extra degrees of freedom, which are only introduced near the
      discontinuity interface. In contrast with most previous methods, restricted to
      sliding motion, no ad hoc penalties or constraints are introduced to reduce gaps
      and overlaps. This allows XFFD to describe more general discontinuous motions. In
      addition, we integrate XFFD into a rigorously formulated multiresolution
      framework by introducing an exact parameter upsampling method. The proposed
      method has been evaluated in two publicly available datasets: 4D pulmonary CT
      images from the DIR-Lab dataset and 4D CT liver datasets. The XFFD achieved a
      Target Registration Error (TRE) of 1.17 +/- 0.85 mm in the DIR-lab dataset and
      1.94 +/- 1.01 mm in the liver dataset, which significantly improves on the
      performance of the state-of-the-art methods handling discontinuities.

PMID- 27894003
TI  - Seizure and Zika virus infection.

PMID- 27894002
TI  - Polymorphism in CRHR1 gene affects the IL-1beta levels in suicidal attempters.
AB  - Approximately one million people commit suicide every year, being suicide
      attempts and ideation even more common. Changes in stress response and activation
      of the immune system have been associated with suicide risk. Here we investigated
      the interaction between immune system and HPA axis alterations in the suicide
      risk, looking for the influence of rs110402 CRHR1 SNP in the IL-1beta levels
      according to suicide ideation and attempt. This study evaluated 171 subjects of
      which 15 had suicidal ideation, 20 had suicide attempt and 136 were controls.
      Genotyping was performed by real-time PCR and IL-1beta levels were measured by
      ELISA. Our data showed that for each point increase in IL-1beta levels the risk
      of suicide attempt increased 5% [relative risk = 1.05 (95% CI: 1.0-1.10)]. After
      sample stratification by rs110402 SNP genotypes, we observed that in subjects
      carrying the A allele the risk raised to 15% [relative risk = 1.15 (95% CI: 1.03
      1.28)], suggesting an apparent effect modification. Thus, this study showed that
      alterations in CRHR1 gene were associated with higher levels of IL-1beta, and
      increased risk for suicide, reinforcing the importance of multifactorial
      interactions of biological markers for psychiatric disorders.

PMID- 27894004
TI  - Online and offline inferential and textual processing of poor comprehenders:
      Evidence from a probing method.
AB  - Numerous studies have demonstrated that poor inferential processing underlies the
      specific deficit of poor comprehenders. However, it is still not clear why poor
      comprehenders have difficulties in generating inferences while reading and
      whether this impairment is general or specific to one or more types of
      inferences. The current study employed an online probing method to examine the
      spontaneous immediate activation of two inference types-forward-predictive
      inferences and backward-explanatory inferences-during reading. In addition, we
      examined the ability of poor comprehenders to retain, suppress, and reactivate
      text information (relevant for inferencing) in working memory. The participants,
      10- to 12-year-old good and poor comprehenders, read short narratives and name
      inference or text word probes following a predictive, intervening, or bridging
      sentence. Comparing the size of probe-naming facilitations revealed that poor
      comprehenders generate predictive inferences, albeit more slowly than good
      comprehenders, and generate explanatory inferences to a lesser extent than good
      comprehenders. Moreover, we found that this inferior inferential processing is
      presumably a result of poor retention and reactivation of inference-evoking text
      information during reading. Finally, poorer reading comprehension was associated
      with higher activation of information when it was less relevant following the
      intervening sentences. Taken together, the current findings demonstrate the
      manner in which poor regulation of relevant and less relevant information during
      reading underlies the specific comprehension difficulties experienced by poor
      comprehenders.

PMID- 27894005
TI  - UPLC-QTOF analysis reveals metabolomic changes in the flag leaf of wheat
      (Triticum aestivum L.) under low-nitrogen stress.
AB  - Wheat is one of the most important grain crop plants worldwide. Nitrogen (N) is
      an essential macronutrient for the growth and development of wheat and exerts a
      marked influence on its metabolites. To investigate the influence of low nitrogen
      stress on various metabolites of the flag leaf of wheat (Triticum aestivum L.), a
      metabolomic analysis of two wheat cultivars under different induced nitrogen
      levels was conducted during two important growth periods based on large-scale
      untargeted metabolomic analysis using ultra-performance liquid chromatography
      quadrupole time-of-flight mass spectrometry (UPLC-QTOF). Multivariate analyses
      such as principle components analysis (PCA) and orthogonal partial least square
      discriminant analysis (OPLS-DA)-were used for data analysis. PCA yielded
      distinctive clustering information among the samples, classifying the wheat flag
      samples into two categories: those under normal N treatment and low N treatment.
      By processing OPLS-DA, eleven secondary metabolites were shown to be responsible
      for classifying the two groups. The secondary metabolites may be considered
      potential biomarkers of low nitrogen stress. Chemical analyses showed that most
      of the identified secondary metabolites were flavonoids and their related
      derivatives, such as iso-vitexin, iso-orientin and methylisoorientin-2"-O
      rhamnoside, etc. This study confirmed the effect of low nitrogen stress on the
      metabolism of wheat, and revealed that the accumulation of secondary metabolites
      is a response to abiotic stresses. Meanwhile, we aimed to identify markers which
      could be used to monitor the nitrogen status of wheat crops, presumably to guide
      appropriate fertilization regimens. Furthermore, the UPLC-QTOF metabolic platform
      technology can be used to study metabolomic variations of wheat under abiotic
      stresses.

PMID- 27894006
TI  - Distinct patterns of imprecise consonant articulation among Parkinson's disease,
      progressive supranuclear palsy and multiple system atrophy.
AB  - Distinct speech characteristics that may aid in differentiation between
      Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple
      system atrophy (MSA) remain tremendously under-explored. Here, the patterns and
      degree of consonant articulation deficits across voiced and voiceless stop
      plosives in 16 PD, 16 PSP, 16 MSA and 16 healthy control speakers were evaluated
      using acoustic and perceptual methods. Imprecise consonant articulation was
      observed across all Parkinsonian groups. Voice onset time of voiceless plosives
      was more prolonged in both PSP and MSA compared to PD, presumably due to greater
      severity of dysarthria and slower articulation rate. Voice onset time of voiced
      plosives was significantly shorter only in MSA, likely as a consequence of damage
      to cerebellar structures. In agreement with the reduction of pre-voicing, MSA
      manifested increased number of voiced plosives misclassified as voiceless at
      perceptual evaluation. Timing of articulatory movements may provide important
      clues about the pathophysiology of underlying disease.

PMID- 27894007
TI  - Infant attention to same- and other-race faces.
AB  - We recorded visual attention to same- and other-race faces in Hispanic and White
      11-month-old infants, an age at which face processing is presumably biased by an
      own-race recognition advantage. Infants viewed pairs of faces differing in race
      or ethnicity as their eye movements were recorded. We discovered consistently
      greater attention to Black over Hispanic faces, to Black faces over White faces,
      and to Hispanic over White faces. Inversion of face stimuli, and infant
      ethnicity, had little effect on performance. Infants' social environments,
      however, differed sharply according to ethnicity: Hispanic infants are almost
      exclusively exposed to Hispanic family members, and White infants to White family
      members. Moreover, Hispanic infants inhabit communities that are more racially
      and ethnically diverse. These results imply that race-based visual attention in
      infancy is closely aligned with the larger society's racial and ethnic
      composition, as opposed to race-based recognition, which is more closely aligned
      with infants' immediate social environments.

PMID- 27894009
TI  - Study of Streptococcus thermophilus population on a world-wide and historical
      collection by a new MLST scheme.
AB  - We analyzed 178 Streptococcus thermophilus strains isolated from diverse
      products, from around the world, over a 60-year period with a new multilocus
      sequence typing (MLST) scheme. This collection included isolates from two
      traditional cheese-making sites with different starter-use practices, in sampling
      campaigns carried out over a three years period. The nucleotide diversity of the
      S. thermophilus population was limited, but 116 sequence types (ST) were
      identified. Phylogenetic analysis of the concatenated sequences of the six
      housekeeping genes revealed the existence of groups confirmed by eBURST analysis.
      Deeper analyses performed on 25 strains by CRISPR and whole-genome analysis
      showed that phylogenies obtained by MLST and whole-genome analysis were in
      agreement but differed from that inferred by CRISPR analysis. Strains isolated
      from traditional products could cluster in specific groups indicating their
      origin, but also be mixed in groups containing industrial starter strains. In the
      traditional cheese-making sites, we found that S. thermophilus persisted on dairy
      equipment, but that occasionally added starter strains may become dominant. It
      underlined the impact of starter use that may reshape S. thermophilus populations
      including in traditional products. This new MLST scheme thus provides a framework
      for analyses of S. thermophilus populations and the management of its
      biodiversity.

PMID- 27894010
TI  - A magnetic resonance imaging study of abnormalities of the patella and patellar
      tendon that predispose children to acute patellofemoral dislocation.
AB  - This study compared 20 children hospitalised with acute patellofemoral
      dislocation with an age-matched healthy control group with no history of knee
      problems or patellar dislocation. The following morphological parameters were
      significantly different between the groups: the mean patellar width and length,
      mean sulcus depth, mean patellar tendon width and total patellar volume. The
      magnetic resonance imaging findings of this study suggested that structurally
      smaller than normal patella and patellar tendon volumes are predisposing factors
      for acute patellofemoral dislocation.

PMID- 27894008
TI  - Common or multiple futures for end of life care around the world? Ideas from the
      'waiting room of history'.
AB  - Around the world there is growing interest in the manner in which care is
      delivered to people at the end of life. However, there is little unanimity on
      what constitutes a 'good death' and the appropriate societal responses to the
      issue of delivering culturally relevant and sustainable forms of end of life care
      in different settings are not subjects of broad agreement. In this critical
      conceptual paper we focus on the emerging narratives of global palliative care
      and offer an assessment of their implications. We relate this to calls to improve
      end of life care across jurisdictions and settings, attempts to map and grade the
      development of palliative care provision, and to the emergence of a widely
      recognised global 'quality of death index'. We consider an alternative approach
      to framing this debate, drawn from a subaltern and post-colonial studies
      perspective and suggest that adopting a truly global perspective will require
      acceptance of the plurality of past and present local problems and issues
      relating to end of life care, as well as the plural possibilities of how they
      might be overcome. In that context, we would not aim to universalise or privilege
      one particular global future for end of life care. Instead of homogenising end of
      life interventions, we seek to be open to multiple futures for the care of the
      dying.

PMID- 27894011
TI  - Comparison of ILAE 2010 and semiological seizure classification in children with
      epilepsy.
AB  - OBJECTIVE: The aim of this study was to compare both ILAE 2010 and semiological
      seizure classification (SSC) in terms of their applicability and utility and to
      predict epileptogenic zone in children with epilepsy. METHODS: Both ILAE 2010
      classification and SSC which is a part of five dimensional classification were
      applied for a total 138 children by dividing into younger (<=6y/o) and older
      (>6y/o) age groups over the last two years as retrospectively. After the
      assessment of the seizures types, epilepsy syndromes, and etiologies; the data
      were also compared to evaluate if having correlation between epileptogenic zone
      and seizure subtypes in both ILAE 2010 and SSC. RESULTS: ILAE 2010 indicated that
      66.7% of the patients had focal seizures, 15.9% had generalized seizures, and
      14.4% had seizures of unknown origin. The SSC revealed that the most frequent
      seizure type was simple seizures (56.5%), second frequent one was complex motor
      seizures (46.4%) and dialeptic seizures (39.9%). To predict epileptogenic zone,
      SSC was found to be more specific than ILAE in terms of the more subgroups of SSC
      were related to the more subgroups of epileptogenic zone (p<0.05). Furthermore,
      there was a clear correlation between focal foci and specific seizure types in
      older ages, while many foci caused to same seizure types and tend to no clear
      focal foci with generalized onset in younger ages. On the other hand, the
      relationship between epileptogenic zone and etiology was more remarkable in the
      five dimensional classification. SIGNIFICANCE: Preference of seizure
      classification system is unique for each patient and depends on requirements.
      Therefore, one dimension cannot be sufficient for evaluation the nature of the
      seizures in some patients. Furthermore, age related evolution of the seizure
      types should not be ignored due to ongoing maturation state of the brain. ILAE
      2010 and SSC have weak and strong points compared to each other. Semiological
      seizure classification is more informative in terms of identifying the
      epileptogenic zone which may be important in specific occasions like pre-surgical
      work up, while ILAE is simple and easier method which can be applied for seizure
      description and their characteristics in daily practice.

PMID- 27894012
TI  - Depression in cancer: The many biobehavioral pathways driving tumor progression.
AB  - Major Depressive Disorder (MDD) is common among cancer patients, with prevalence
      rates up to four-times higher than the general population. Depression confers
      worse outcomes, including non-adherence to treatment and increased mortality in
      the oncology setting. Advances in the understanding of neurobiological
      underpinnings of depression have revealed shared biobehavioral mechanisms may
      contribute to cancer progression. Moreover, psychosocial stressors in cancer
      promote: (1) inflammation and oxidative/nitrosative stress; (2) a decreased
      immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous
      system and of the hypothalamic-pituitaryadrenal axis. Consequently, the prompt
      recognition of depression among patients with cancer who may benefit of treatment
      strategies targeting depressive symptoms, cognitive dysfunction, fatigue and
      sleep disturbances, is a public health priority. Moreover, behavioral strategies
      aiming at reducing psychological distress and depressive symptoms, including
      addressing unhealthy diet and life-style choices, as well as physical inactivity
      and sleep dysfunction, may represent important strategies not only to treat
      depression, but also to improve wider cancer-related outcomes. Herein, we provide
      a comprehensive review of the intertwined biobehavioral pathways linking
      depression to cancer progression. In addition, the clinical implications of these
      findings are critically reviewed.

PMID- 27894014
TI  - A fast approach to 3D HSQC-based spectroscopy based on a Fourier phase encoding
      of pre-targeted resonances.
AB  - Multidimensional Nuclear Magnetic Resonance (NMR) provides a unique window into
      structure and dynamics at an atomic level. Traditionally, given the scan-by-scan
      time modulation involved in these experiments, the duration of nD NMR increases
      exponentially with spectral dimensionality. In addition, acquisition times
      increase as the number of spectral elements being sought in each indirect domain 
      given by the ratio between the spectral bandwidth being targeted and the
      resolution desired. These long sampling times can be substantially reduced by
      exploiting information that is often available from lower-dimensionality
      acquisitions. This work presents a novel approach that exploits previous 2D
      information to speed up the acquisition of 3D spectra, based on what we denote as
      a Time-Optimized FouriEr Encoding (TOFEE) of pre-targeted peaks. Such 3D TOFEE
      experiments, which present points in common with Hadamard-encoded 3D
      acquisitions, do not necessarily require more scans than their 2D counterparts.
      This is here demonstrated based on extensions of 2D Heteronuclear Single-quantum
      Coherence (HSQC) experiments, to 3D HSQC-TOCSY or 3D HSQC-NOESY acquisitions. The
      theoretical basis of this new approach is given, and experimental demonstrations
      are presented on small molecule and protein-based model systems.

PMID- 27894015
TI  - Examining associations between area-level spatial measures of housing with
      selected health and wellbeing behaviours and outcomes in an urban context.
AB  - Adequate and affordable housing is a major social determinant of health; yet no
      work has attempted to conceptually map and spatially test area-level measures of
      housing with selected health and wellbeing outcomes. Sourcing data from 7,753
      adults from Melbourne, Australia, we tested associations between area-level
      measures of housing density, tenure, and affordability with individual-level
      measures of neighbourhood safety, community satisfaction, and self-rated health.
      Compared with the reference groups, the odds of: feeling unsafe was higher for
      residents living in areas with less affordable housing; community dissatisfaction
      was ~30% higher in those living in areas with >36% residential properties
      assigned as rentals, and was significantly higher in the least affordable areas
      (OR =1.57). Compared with the reference groups, as dwelling density, proportion
      of rental properties, and housing unaffordability increased, the odds of
      reporting poorer self-rated health increased; however these associations did not
      always reach statistical significance. This work highlights the benefits of
      evidenced-based planning spatial measures to support health and wellbeing.

PMID- 27894013
TI  - Outer membrane protein design.
AB  - Membrane proteins are the gateway to the cell. These proteins are also a control
      center of the cell, as information from the outside is passed through membrane
      proteins as signals to the cellular machinery. The design of membrane proteins
      seeks to harness the power of these gateways and signal carriers. This review
      will focus on the design of the membrane proteins that are in the outer membrane,
      a membrane which only exists for gram negative bacteria, mitochondria, and
      chloroplasts. Unlike other membrane proteins, outer membrane proteins are
      uniquely shaped as beta-barrels. Herein, I describe most known examples of
      membrane beta-barrel design to date, focusing particularly on categorizing
      designs as: Firstly, structural deconstruction; secondly, structural changes;
      thirdly, chemical function design; and finally, the creation of new folds.

PMID- 27894016
TI  - Adolescents who engage in active school transport are also more active in other
      contexts: A space-time investigation.
AB  - BACKGROUND: Although active school travel (AST) is important for increasing
      moderate-to-vigorous physical activity (MVPA), it is unclear how AST is related
      to context-specific physical activity and non-school travel. This study
      investigated how school travel is related to physical activity and travel
      behaviours across time- and space-classified domains. METHODS: A total of 196
      adolescents wore a Global Positioning System receiver and an accelerometer for 7
      days. All data were classified into one of four domains: home, school, transport,
      or leisure. Generalized linear mixed models were used to compare domain-specific
      PA and non-school trips between active and passive school travellers. RESULTS:
      Active travellers accumulated 13 and 14 more min of MVPA on weekdays and weekend
      days, respectively. They also spent 15min less time in vehicular travel during
      non-school trips, and accrued an additional 9min of MVPA while walking on weekend
      days. However, those with no AST still achieved most of their MVPA in the
      transport domain. CONCLUSIONS: AST is related to out-of-school physical activity
      and transportation, but transport is also important for those who do not use AST.
      As such, future studies should consider overall mobility and destinations other
      than school when assessing travel and physical activity behaviours.

PMID- 27894017
TI  - The regional geography of alcohol consumption in England: Comparing drinking
      frequency and binge drinking.
AB  - Alcohol consumption frequency and volume are known to be related to health
      problems among drinkers. Most of the existing literature that analyses regional
      variation in drinking behaviour uses measures of consumption that relate only to
      volume, such as 'binge drinking'. This study compares the regional association of
      alcohol consumption using measures of drinking frequency (daily drinking) and
      volume (binge drinking) using a nationally representative sample of residents
      using the Health Survey for England, 2011-2013. Results suggest the presence of
      two differentiated drinking patterns with relevant policy implications. We find
      that people in northern regions are more likely to binge drink, whereas people in
      southern regions are more likely to drink on most days. Regression analysis shows
      that regional variation in binge drinking remains strong when taking into account
      individual and neighbourhood level controls. The findings provide support for
      regional targeting of interventions that aim to reduce the frequency as well as
      volume of drinking.

PMID- 27894018
TI  - Managing mosquito spaces: Citizen self-governance of disease vectors in a desert
      landscape.
AB  - Public health agencies' strategies to control disease vectors have increasingly
      included "soft" mosquito management programs that depend on citizen education and
      changing homeowner behaviors. In an effort to understand public responses to such
      campaigns, this research assesses the case of Tucson, Arizona, where West Nile
      virus presents a serious health risk and where management efforts have focused on
      public responsibility for mosquito control. Using surveys, interviews, and focus
      groups, we conclude that citizens have internalized responsibilities for mosquito
      management but also expect public management of parks and waterways while tending
      to reject the state's interference with privately owned parcels. Resident
      preferences for individualized mosquito management hinge on the belief that
      mosquito-borne diseases are not a large threat, a pervasive distrust of state
      management, and a fear of the assumed use of aerial pesticides by state managers.
      Opinions on who is responsible for mosquitoes hinge on both perceptions of
      mosquito ecology and territorial boundaries, with implications for future disease
      outbreaks.

PMID- 27894020
TI  - The anatomical mummies of Mombello: detection of cocaine, nicotine, and caffeine
      in the hair of psychiatric patients of the early 20th century.
AB  - The Mombello Psychiatric Hospital in Limbiate, near Milan, replaced the old
      Senavra Hospital as the Psychiatric Hospital for the Province of Milan in the
      19th century. During the early 20th century, bodies of several Mombello patients
      were dissected and preserved by Giuseppe Paravicini, an anatomist who operated
      within the asylum. The aim of the present study was to examine and memorialize
      this important assemblage. To this end, we were allowed to sample the head hair
      of six such preparations for toxicological analysis. By means of high performance
      liquid chromatography, cocaine and its main metabolite, benzoylecgonine, were
      detected in two out of six hair samples. The concentrations for cocaine were
      0.151 and 0.09ng/mg and for benzoylecgonine 0.103 and 0.147ng/mg, respectively.
      Given that cocaine was a commonly used medicine, beginning in the mid-19th
      century and persisting into the 20th century, it is not surprising that some
      patients may have ingested this drug. In addition to the detection of cocaine,
      these analyses also provided evidence of nicotine and caffeine intake.

PMID- 27894019
TI  - Elucidating a chemical defense mechanism of Antarctic sponges: A computational
      study.
AB  - In 2000, a novel secondary metabolite (erebusinone, Ereb) was isolated from the
      Antarctic sea sponge, Isodictya erinacea. The bioactivity of Ereb was
      investigated, and it was found to inhibit molting when fed to the arthropod
      species Orchomene plebs. Xanthurenic acid (XA) is a known endogenous molt
      regulator present in arthropods. Experimental studies have confirmed that XA
      inhibits molting by binding to either (or both) of two P450 enzymes (CYP315a1 or
      CYP314a1) that are responsible for the final two hydroxylations in the production
      of the molt-inducing hormone, 20-hydroxyecdysone (20E). The lack of crystal
      structures and biochemical assays for CYP315a1 or CYP314a1, has prevented further
      experimental exploration of XA and Ereb's molt inhibition mechanisms. Herein, a
      wide array of computational techniques - homology modeling, molecular dynamics
      simulations, binding site bioinformatics, flexible receptor-flexible ligand
      docking, and molecular mechanics-generalized Born surface area calculations -
      have been employed to elucidate the structure-function relationships between the
      aforementioned P450s and the two described small molecule inhibitors (Ereb and
      XA). Results indicate that Ereb likely targets CYP315a1 by interacting with a
      network of aromatic residues in the binding site, while XA may inhibit both
      CYP315a1 and CYP314a1 because of its aromatic, as well as charged nature.

PMID- 27894021
TI  - Toxicity of silver ions and differently coated silver nanoparticles in Allium
      cepa roots.
AB  - Silver nanoparticles (AgNPs) are the dominating nanomaterial in consumer products
      due to their well-known antibacterial and antifungal properties. To enhance their
      properties, different surface coatings may be used, which affect physico-chemical
      properties of AgNPs. Due to their wide application, there has been concern about
      possible environmental and health consequences. Since plants play a significant
      role in accumulation and biodistribution of many environmentally released
      substances, they are also very likely to be influenced by AgNPs. In this study we
      investigated the toxicity of AgNO3 and three types of laboratory-synthesized
      AgNPs with different surface coatings [citrate, polyvinylpyrrolidone (PVP) and
      cetyltrimethylammonium bromide (CTAB)] on Allium cepa roots. Ionic form of Ag was
      confirmed to be more toxic than any of the AgNPs applied. All tested AgNPs caused
      oxidative stress and exhibited toxicity only when applied in higher
      concentrations. The highest toxicity was recorded for AgNPs-CTAB, which resulted
      with increased Ag uptake in the roots, consequently leading to strong reduction
      of the root growth and oxidative damage. The weakest impact was found for AgNPs
      citrate, much bigger, negatively charged NPs, which also aggregated to larger
      particles. Therefore, we can conclude that the toxicity of AgNPs is directly
      correlated with their size, overall surface charge and/or surface coating.

PMID- 27894022
TI  - Changes in nitric oxide/hydrogen peroxide content and cell cycle progression:
      Study with synchronized cultures of green alga Chlamydomonas reinhardtii.
AB  - The present study aimed to evaluate the possible relationship between the changes
      in hydrogen peroxide (H2O2) and nitric oxide (NO) content and the course of
      growth and reproductive processes of the cell cycle of Chlamydomonas reinhardtii.
      The peak of H2O2 observed at the beginning of the cell cycle was found to
      originate from Fe-SOD and Mn-SODchl. activity and result from the alternation in
      the photosynthetic processes caused by the dark-to-light transition of daughter
      cells. A rapid increase in NO concentration, observed before the light-to-dark
      cell transition, originated from NR and NIR activity and was followed by a
      photosynthesis-independent, Mn-SODchl.-mediated increases in H2O2 production.
      This H2O2 peak overlapped the beginning of Chlamydomonas cell division, which was
      indicated by a profile of CYCs and CDKs characteristic of cells' passage through
      the G1/S and S/M checkpoints. Taken together, our results show that there is a
      clear relationship between the course of the Chlamydomonas cell cycle and typical
      changes in the H2O2/NO ratio, as well as changes in expression and activity of
      enzymes involved in generation and scavenging of these signaling molecules.

PMID- 27894023
TI  - Persistent generalized periodic discharges: A specific marker of fatal outcome in
      cerebral hypoxia.
AB  - OBJECTIVES: Electroencephalography (EEG) is one of the methods used in predicting
      the outcome after cerebral hypoxia. In this study we aim to evaluate the
      significance of generalized periodic discharges (GPD) as a prognostic marker.
      METHODS: We retrospectively analyzed the medical histories of patients, who
      underwent an EEG after cardiac arrest during the time period from 2005 to 2013 at
      the University Hospital Zurich. All EEGs were re-interpreted using the 2012
      American Clinical Neurophysiology Society (ACNS) classification for intensive
      care unit (ICU) EEGs. RESULTS: Out of 131 patients, in which an EEG was recorded
      after cardiopulmonary resuscitation, 119 were included in our study. The average
      interval between cardiac arrest and EEG-recording was 3.8+/-3.0days (range: 0
      14days). Persistent GPDs (i.e. GPDs more than 24h after the event) were found in
      thirty-two (26.9%) of the patients initial EEGs. The appearance of persistent
      GPDs preceded fatal outcome in 100% of all cases (vs. 69.0% in the non-GPD-group,
      p<0.0001). CONCLUSION: Among other encephalopathic markers in EEG persistent GPDs
      are a highly specific prognostic marker of fatal outcome in patients with hypoxic
      encephalopathy. SIGNIFICANCE: Using standardized EEG interpretation, this study
      identified persistent GPDs as a specific prognostic marker in post cardiac arrest
      syndrome.

PMID- 27894024
TI  - Foot placement during error and pedal applications in naturalistic driving.
AB  - Data from a naturalistic driving study was used to examine foot placement during
      routine foot pedal movements and possible pedal misapplications. The study
      included four weeks of observations from 30 drivers, where pedal responses were
      recorded and categorized. The foot movements associated with pedal
      misapplications and errors were the focus of the analyses. A random forest
      algorithm was used to predict the pedal application types based the video
      observations, foot placements, drivers' characteristics, drivers' cognitive
      function levels and anthropometric measurements. A repeated multinomial logit
      model was then used to estimate the likelihood of the foot placement given
      various driver characteristics and driving scenarios. The findings showed that
      prior foot location, the drivers' seat position, and the drive sequence were all
      associated with incorrect foot placement during an event. The study showed that
      there is a potential to develop a driver assistance system that can reduce the
      likelihood of a pedal error.

PMID- 27894025
TI  - Fixating on the size-speed illusion of approaching railway trains: What we can
      learn from our eye movements.
AB  - Railway level crossing collisions have recently been linked to a size-speed
      illusion where larger objects such as trains appear to move slower than smaller
      objects such as cars. An explanation for this illusion has centred on observer
      eye movements - particularly in relation to the larger, longer train. A previous
      study (Clark et al., 2016) found participants tend to make initial fixations to
      locations around the visual centroid of a moving vehicle; however individual eye
      movement patterns tended to be either fixation-saccade-fixation type, or smooth
      pursuit. It is therefore unknown as to which type of eye movement contributes to
      the size-speed illusion. This study isolated fixation eye movements by requiring
      participants to view computer animated sequences in a laboratory setting, where a
      static fixation square was placed in the foreground at one of two locations on a
      train (front and centroid). Results showed that even with the square placed
      around the front location of a vehicle, participants still underestimated the
      speed of the train relative to the car and underestimation was greater when the
      square was placed around the visual centroid of the train. Our results verify
      that manipulation of eye movement behaviour can be effective in reducing the
      magnitude of the size-speed illusion and propose that interventions based on this
      manipulation should be designed and tested for effectiveness.

PMID- 27894026
TI  - The effect of road network patterns on pedestrian safety: A zone-based Bayesian
      spatial modeling approach.
AB  - Pedestrian safety is increasingly recognized as a major public health concern.
      Extensive safety studies have been conducted to examine the influence of multiple
      variables on the occurrence of pedestrian-vehicle crashes. However, the explicit
      relationship between pedestrian safety and road network characteristics remains
      unknown. This study particularly focused on the role of different road network
      patterns on the occurrence of crashes involving pedestrians. A global integration
      index via space syntax was introduced to quantify the topological structures of
      road networks. The Bayesian Poisson-lognormal (PLN) models with conditional
      autoregressive (CAR) prior were then developed via three different proximity
      structures: contiguity, geometry-centroid distance, and road network
      connectivity. The models were also compared with the PLN counterpart without
      spatial correlation effects. The analysis was based on a comprehensive crash
      dataset from 131 selected traffic analysis zones in Hong Kong. The results
      indicated that higher global integration was associated with more pedestrian
      vehicle crashes; the irregular pattern network was proved to be safest in terms
      of pedestrian crash occurrences, whereas the grid pattern was the least safe; the
      CAR model with a neighborhood structure based on road network connectivity was
      found to outperform in model goodness-of-fit, implying the importance of
      accurately accounting for spatial correlation when modeling spatially aggregated
      crash data.

PMID- 27894027
TI  - Assessing the safety effects of cooperative intelligent transport systems: A
      bowtie analysis approach.
AB  - The safety effects of cooperative intelligent transport systems (C-ITS) are
      mostly unknown and associated with uncertainties, because these systems represent
      emerging technology. This study proposes a bowtie analysis as a conceptual
      framework for evaluating the safety effect of cooperative intelligent transport
      systems. These seek to prevent road traffic accidents or mitigate their
      consequences. Under the assumption of the potential occurrence of a particular
      single vehicle accident, three case studies demonstrate the application of the
      bowtie analysis approach in road traffic safety. The approach utilizes exemplary
      expert estimates and knowledge from literature on the probability of the
      occurrence of accident risk factors and of the success of safety measures. Fuzzy
      set theory is applied to handle uncertainty in expert knowledge. Based on this
      approach, a useful tool is developed to estimate the effects of safety-related
      cooperative intelligent transport systems in terms of the expected change in
      accident occurrence and consequence probability.

PMID- 27894028
TI  - Exploring the clinical decision-making used by experienced cardiorespiratory
      physiotherapists: A mixed method qualitative design of simulation, video
      recording and think aloud techniques.
AB  - BACKGROUND: The ability of physiotherapists to make clinical decisions is a vital
      component of being an autonomous practitioner, yet this complex phenomenon has
      been under-researched in cardiorespiratory physiotherapy. The purpose of this
      study was to explore clinical decision-making (CDM) by experienced
      physiotherapists in a scenario of a simulated patient experiencing acute
      deterioration of their respiratory function. OBJECTIVES: The main objective of
      this observational study was to identify the actions, thoughts, and behaviours
      used by experienced cardiorespiratory physiotherapists in their clinical decision
      making processes. DESIGN: A mixed-methods (qualitative) design employing
      observation and think-aloud, was adopted using a computerised manikin in a
      simulated environment. SETTING: The participants clinically assessed the manikin
      programmed with the same clinical signs, under standardised conditions in the
      clinical skills practice suite, which was set up as a ward environment.
      PARTICIPANTS: Experienced cardiorespiratory physiotherapists, recruited from
      clinical practice within a 50-mile radius of the University(*). METHODS:
      Participants were video-recorded throughout the assessment and treatment and
      asked to verbalise their thought processes using the 'think-aloud' method. The
      recordings were transcribed verbatim and managed using a Framework approach.
      RESULTS: Eight cardiorespiratory physiotherapists participated (mean 7years
      clinical experience, range 3.5-16years. CDM was similar to the collaborative
      hypothetico-deductive model, five-rights nursing model, reasoning strategies,
      inductive reasoning and pattern recognition. However, the CDM demonstrated by the
      physiotherapists was complex, interactive and iterative. Information processing
      occurred continuously throughout the whole interaction with the patient, and the
      specific cognitive skills of recognition, matching, discriminating, relating,
      inferring, synthesising and prediction were identified as being used
      sequentially. CONCLUSIONS: The findings from this study were used to develop a
      new conceptual model of clinical decision-making for cardiorespiratory
      physiotherapy. This conceptual model can be used to inform future educational
      strategies to prepare physiotherapists and nurses for working in acute
      respiratory care.

PMID- 27894029
TI  - College student marijuana involvement: Perceptions, use, and consequences across
      11 college campuses.
AB  - BACKGROUND: Marijuana is currently the most commonly used illicit drug in the
      United States, and with the movement toward legalization of recreational
      marijuana, the country faces numerous issues regarding policy, prevention, and
      treatment of marijuana use. The present study examines the prevalence of
      marijuana use and consequences and compares users and non-users on a wide range
      of other marijuana-related constructs among college students across 11
      universities. METHOD: Participants included 8141 college students recruited from
      the psychology department participant pools of 11 universities throughout the US,
      including four major regions of the US (West, South, Midwest, Northeast) and
      states with varying policies regarding the legality of marijuana use. RESULTS: We
      observed marijuana use rates similar to representative samples of young adults
      and college students (i.e., 53.3% lifetime marijuana users, 26.2% past month
      marijuana users). About 1 in 10 past month marijuana users experienced no
      consequences from their use, whereas nearly 1 in 10 experienced 19 or more
      consequences. Lifetime marijuana users had more positive perceptions of marijuana
      compared to non-users on a wide-range of marijuana-related constructs.
      CONCLUSIONS: We report descriptive statistics on a wide range of marijuana
      related variables. We hope that these data provide a useful baseline prior to
      increased legalization of recreational marijuana use. Multi-site studies like
      this one are needed to study the risky and protective factors for problematic
      marijuana use. These findings can inform interventions and public policy.

PMID- 27894030
TI  - Fatigue in hospital nurses - 'Supernurse' culture is a barrier to addressing
      problems: A qualitative interview study.
AB  - BACKGROUND: Fatigue in hospital nurses is associated with decreased nurse
      satisfaction, increased turnover and negative patient outcomes. Addressing
      fatigue in nurses has been identified as a priority by many organizations
      worldwide in an effort to promote both a culture of patient safety and a healthy
      nursing workforce. OBJECTIVES: The overall aim of this study was to explore
      barriers and facilitators within the hospital nurse work system to nurse coping
      and fatigue. The purpose of this paper is to describe emergent themes that offer
      new insight describing the relationships among nurse perceptions of fatigue,
      nursing professional culture, and implications for the nursing workforce. DESIGN:
      A qualitative exploratory study was used to explore nurse identified sources,
      barriers to addressing, and consequences of fatigue. PARTICIPANTS AND SETTING:
      Twenty-two nurses working in intensive care and medical-surgical units within a
      large academic medical center in the United States participated in the
      interviews. METHOD: Interviews with the participants followed a semi-structured
      interview guide that included questions eliciting participants' views on nurse
      fatigue levels, consequences of fatigue, and barriers to addressing fatigue. The
      interview transcripts were analyzed using directed content analysis guided by the
      Systems Engineering Initiative for Patient Safety (SEIPS) model. Additional
      themes that did not directly align with the SEIPS model were also identified.
      RESULTS: All nurses in the current study experienced fatigue; yet they had
      varying perspectives on the importance of addressing fatigue in relation to other
      health systems challenges. A new construct related to nursing professional
      culture was identified and defined as "Supernurse". Identified subthemes of
      Supernurse include: extraordinary powers used for good; cloak of invulnerability;
      no sidekick; Kryptonite, and an alterego. These values, beliefs, and behaviors
      define the specific aspects of nursing professional culture that can act as
      barriers to fatigue risk management programs and achieving safety culture in
      hospital organizations. Nurse fatigue and attributes of nurse professional
      culture also have implications for nurse satisfaction and retention. CONCLUSIONS:
      Findings from this study further support the role of nursing professional culture
      as an important barrier to effectively addressing fatigue in nursing work
      systems. Future work is needed to identify and evaluate innovative culture change
      models and strategies to target these barriers.

PMID- 27894031
TI  - Artificial placenta: Analysis of recent progress.
AB  - The artificial placenta (AP) has for many decades captured the imagination of
      scientists and authors with popular fiction including The Matrix and Aldous
      Huxley's "Brave New World", depicting a human surviving ex-utero in an artificial
      uterine environment (AUE). For scientists this has fascinated as a way forward
      for extremely preterm infants (EPIs) born less than 28 weeks of gestation. Early
      successes with mechanical ventilation (MV) for infants born above 28 weeks of
      gestation meant that AP research lost momentum. More recently, the gestational
      age limit for survival now borders on 23 weeks and corresponds to the biological
      milestone of lung development marked by the early canalicular stage of lung
      morphogenesis. The so called greyzone of 23-25 weeks represents a steep increase
      in mortality with decreasing gestational age and current options in neonatal care
      are on the fringes of efficacy for this population. A shift in thinking
      recognizes the vitality of EPIs as a fetus rather than a 37-40 week neonate and
      this has reinvigorated the concept of the AP. This review will discuss the scale
      of extreme preterm birth with special reference to previable infants born in the
      greyzone. Recent AP studies using sheep models are compared, technical obstacles
      discussed and future research themes identified.

PMID- 27894032
TI  - Clinical outcomes in women undergoing laparoscopic hysteropexy: A systematic
      review.
AB  - OBJECTIVES: To systematically review the current evidence on the anatomic and
      functional outcomes in women undergoing laparoscopic hysteropexy. STUDY DESIGN:
      An electronic database search was undertaken (2000-2016). Keywords were:
      "laparoscopy", "hysteropexy", "cervicopexy", "uterine suspension", "uterosacral
      plication". References of identified studies as well as abstracts from
      conferences were considered. We restricted the search to humans, female patients
      and currently used surgical procedures. Studies with >=5 cases in English
      language and published in 2000 or later, were included. After the initial yield,
      studies were selected following title screening, abstract and full text scrutiny.
      RESULTS: A total of 17 studies were deemed suitable for inclusion in the review.
      A total of 770 patients in 17 studies received the intervention being studied
      (laparoscopic hysteropexy) and were assessed post-operatively with pooled success
      rates of 85.32% (95%CI: +/-2.5). Laparoscopic suture hysteropexy has pooled
      success of 70.5% (95%CI:+/-5.33) whereas the pooled success of the suspension to
      the sacral promontory using mesh or tape is 92% (95%CI: +/-2.53). One small study
      on suspension to the anterior abdominal wall (28 cases) and one to the pectineal
      ligament (18 cases) have shown 96.4% (95%CI:+/-6.9) and 94.5% (95%CI:+/-10.53)
      objective success rates respectively. CONCLUSION: Laparoscopic hysteropexy was
      associated with good anatomic cure rates of greater than 90% in majority of the
      studies. There was an improvement in symptoms, and good subjective cure rates in
      73%-100% of the patients. Reoperation rates were low in most studies ranging from
      around 0%-28%. Complications rates were generally low. Laparoscopic hysteropexy
      is a feasible alternative for women needing surgical correction of uterovaginal
      prolapse and who desire conservation of the uterus.

PMID- 27894033
TI  - The age-related recurrence of endometrioma after conservative surgery.
AB  - OBJECTIVE: As endometrioma frequently recurs after conservative surgery, long
      term postoperative medical treatment for the prevention of recurrence is
      necessary. However, it has not been elucidated whether long-term postoperative
      medical treatment is crucial to all patients until menopause. Thereupon, this
      study was conducted to evaluate the age-related recurrence patterns after
      conservative surgery for endometrioma. STUDY DESIGN: A retrospective cohort study
      was performed on a total of 420 reproductive-aged women who underwent
      conservative surgery for endometrioma between January 2000 and December 2010.
      Ultrasonography was used during the follow-up period to detect endometrioma
      recurrence. Patients were classified into two groups according to the use of
      postoperative medications. The first group was observation only, while the second
      received gonadotropin releasing hormone agonists followed by cyclic oral
      contraceptives. The cumulative recurrence rate of endometrioma was compared
      according to the age at surgery (20-29 years, 30-39 years, 40-45 years) within
      each group. Subgroup analysis was performed according to the age between the two
      groups. RESULTS: The median follow-up duration after surgery was 29.0 months
      (range 6-159 months) for all patients. After adjusting for parity, size and
      bilaterality of cyst, and stage with American Society for Reproductive Medicine
      classification of endometriosis which was statistically different, within the
      group of no treatment, the cumulative recurrence rate in 40-45 years (10.2%) was
      significantly lower compared with those in 20-29 years (43.3%; hazard ratio
      (HR)=0.04; 95% confidence interval (CI)=0.01-0.52) and 30-39 years (22.5%;
      HR=0.19; 95% CI=0.04-0.92). However, there were no differences within the group
      of postoperative medical treatment. When we compared between the two groups, the
      cumulative recurrence rate was significantly different in 20-29 years (8.1 vs
      43.3%; p<0.001) and 30-39 years (5.4 vs 22.5%; p=0.007), but there was no
      difference in 40-45 years (4.5 vs 10.2%; p=0.901). CONCLUSIONS: Our preliminary
      results demonstrate that the risk of endometrioma recurrence decreases with age.
      After the age of forty, the recurrence rate does not differ according to the use
      of postoperative medication. Based on our results, postoperative medical
      treatment may be individualized according to the patient's age at the time of
      surgery. Further studies are needed to identify patients who may benefit from
      postoperative medication.

PMID- 27894034
TI  - Quality of life after UpholdTM Vaginal Support System surgery for apical pelvic
      organ prolapse-A prospective multicenter study.
AB  - OBJECTIVE: To study the effects on quality of life in women operated for apical
      pelvic organ prolapse using the Vaginal UpholdTM System. STUDY DESIGN: In this
      prospective cohort study, women (n=207) with symptomatic apical prolapse, with or
      without cystocele, were operated using the UpholdTM Vaginal Support System.
      Follow-up for quality of life was performed at 12 months after surgery, and
      assessed by the PFDI-20, and PFIQ-7, and sexual function by the PISQ-12. We used
      odds ratios (ORs) with 95% confidence intervals (CIs) for outcome association
      analyses using logistic regression. RESULTS: At one-year follow-up majority of
      women experienced an overall postoperative improvement in quality of life
      (p<0.001). One year after surgery UpholdTM operation alone increased the risk for
      prolapse related bother as compared to UpholdTM combined with anterior
      colporraphy (POP-IQ-7; OR 2.1; 95% CI 1.01-4.3). The frequency of dyspareunia
      decreased postoperatively (p=0.004), however, after one-year, overall sexual
      function deteriorated significantly (p<0.001). The worsening in sexual function
      scores was mainly attributed to the partner related domain, whereas the
      behavioral-emotive and physical domains showed no significant changes.
      CONCLUSION: Apical prolapse repair using UpholdTM improved quality of life among
      our patients but worsened overall sexual function postoperatively.

PMID- 27894035
TI  - An isothermal, label-free, and rapid one-step RNA amplification/detection assay
      for diagnosis of respiratory viral infections.
AB  - Recently, RNA viral infections caused by respiratory viruses, such as influenza,
      parainfluenza, respiratory syncytial virus, coronavirus, and Middle East
      respiratory syndrome-coronavirus (MERS-CoV), and Zika virus, are a major public
      health threats in the world. Although myriads of diagnostic methods based on RNA
      amplification have been developed in the last decades, they continue to lack
      speed, sensitivity, and specificity for clinical use. A rapid and accurate
      diagnostic method is needed for appropriate control, including isolation and
      treatment of the patients. Here, we report an isothermal, label-free, one-step
      RNA amplification and detection system, termed as iROAD, for the diagnosis of
      respiratory diseases. It couples a one-step isothermal RNA amplification method
      and a bio-optical sensor for simultaneous viral RNA amplification/detection in a
      label-free and real-time manner. The iROAD assay offers a one-step viral RNA
      amplification/detection example to rapid analysis (<20min). The detection limit
      of iROAD assay was found to be 10-times more sensitive than that of real-time
      reverse transcription-PCR method. We confirmed the clinical utility of the iROAD
      assay by detecting viral RNAs obtained from 63 human respiratory samples. We
      envision that the iROAD assay will be useful and potentially adaptable for better
      diagnosis of emerging infectious diseases including respiratory diseases.

PMID- 27894036
TI  - Efficacy of an adjunctive brief psychodynamic psychotherapy to usual inpatient
      treatment of depression: Results of a randomized controlled trial.
AB  - BACKGROUND: For severe and chronic depression, inpatient treatment may be
      necessary. Current guidelines recommend combined psychological and
      pharmacological treatments for moderate to severe depression. Results for
      positive effects of combined treatment for depressed inpatients are still
      ambiguous. METHODS: This randomised controlled trial examined the efficacy of
      adding an intensive and brief psychodynamic psychotherapy (IBPP) to treatment-as
      usual (TAU) for inpatients with DSM-IV major depressive episode. The primary
      outcomes were reduction in depression severity, and response and remission rates
      at post-treatment, 3-month and 12-month follow-up points. RESULTS: A linear mixed
      model analysis (N=149) showed a higher reduction in the observer-rated severity
      of depressive symptoms at each follow-up point for the IBPP condition compared
      with the TAU condition (post-treatment ES=0.39, 95%CI 0.06-0.71; 3-month ES=0.46,
      95%CI 0.14-0.78; 12-month ES=0.32, 95%CI 0.01-0.64). Response rate was superior
      in the IBPP group compared with the TAU group at all follow-up points (post
      treatment OR =2.69, 95%CI 1.18-6.11; 3-month OR=3.47, 95%CI 1.47-8.25; 12-month
      OR=2.26, 95%CI 1.02-4.97). IBPP patients were more likely to be remitted 3 months
      (OR=2.82, 95%CI 1.12-7.10) and 12 months (OR=2.93, 95%CI 1.12-7.68) after
      discharge than TAU patients. LIMITATIONS: Heterogeneous sample with different
      subtypes of depression and comorbidity. CONCLUSIONS: IBPP decreased observer
      rated depression severity up to 12 months after the end of treatment. IBPP
      demonstrated immediate and distant treatment responses as well as substantial
      remissions at follow-up. IBPP appears to be a valuable adjunct in the treatment
      of depressed inpatients.

PMID- 27894037
TI  - Psychopathology profiles of acutely suicidal adolescents: Associations with post
      discharge suicide attempts and rehospitalization.
AB  - BACKGROUND: Suicidal adolescents are heterogeneous, which can pose difficulties
      in predicting suicidal behavior. The Youth Self-Report (YSR) psychopathology
      profiles predict the future onset of psychopathology and suicide-related
      outcomes. The present study examined the prevalence and correlates of YSR
      psychopathology profiles among suicidal adolescents and prospective associations
      with post-discharge rates of suicide attempts and psychiatric rehospitalization.
      METHODS: Participants were acutely suicidal, psychiatrically hospitalized
      adolescents (N=433 at baseline; n=355 at follow-up) who were enrolled in a
      psychosocial intervention trial during hospitalization. Psychopathology profiles
      were assessed at baseline. Suicide attempts and rehospitalization were assessed
      for up to 12 months following discharge. RESULTS: Latent profile analysis
      identified four psychopathology profiles: subclinical, primarily internalizing,
      and moderately and severely dysregulated. At baseline, profiles differed by
      history of non-suicidal self-injury (NSSI) and multiple suicide attempts (MA) as
      well as severity of suicide ideation, hopelessness, depressive symptoms, anxiety
      symptoms, substance abuse, and functional impairment. The dysregulation profiles
      predicted suicide attempts within 3 months post-discharge. The internalizing
      profile predicted suicide attempts and rehospitalization at 3 and 12 months.
      LIMITATIONS: This study's participants were enrolled in a randomized trial and
      were predominantly female, which limit generalizability. Additionally, only a
      history of NSSI was assessed. CONCLUSIONS: The dysregulation profile was
      overrepresented among suicidal youth and associated with impairment in several
      domains as well as suicide attempts shortly after discharge. Adolescents with a
      severe internalizing profile also reported adverse outcomes throughout the study
      period. Psychopathology profiles warrant further examination in terms of their
      potential predictive validity in relation to suicide-related outcomes.

PMID- 27894038
TI  - Fast microwave-assisted catalytic co-pyrolysis of lignin and low-density
      polyethylene with HZSM-5 and MgO for improved bio-oil yield and quality.
AB  - Fast microwave-assisted catalytic co-pyrolysis of lignin and low-density
      polyethylene (LDPE) with HZSM-5 and MgO was investigated. Effects of pyrolysis
      temperature, lignin to LDPE ratio, MgO to HZSM-5 ratio, and feedstock to catalyst
      ratio on the products yields and chemical profiles were examined. 500 degrees C
      was the optimal co-pyrolysis temperature in terms of the maximum bio-oil yield.
      The proportion of aromatics increased with increasing LDPE content. In addition,
      with the addition of LDPE (lignin/LDPE=1/2), methoxyl group in the phenols was
      completely removed. A synergistic effect was found between lignin and LDPE. The
      proportion of aromatics increased and alkylated phenols decreased with increasing
      HZSM-5 to MgO ratio. The bio-oil yield increased with the addition of appropriate
      amount of catalyst and the proportion of alkylated phenols increased with
      increasing catalyst to feedstock ratio.

PMID- 27894039
TI  - Biochar amendment for integrated composting and vermicomposting of sewage sludge 
      The effect of biochar on the activity of Eisenia fetida and the obtained
      vermicompost.
AB  - Sewage sludge derived biochar (SSDB) was used as a supplementary material for
      municipal sewage sludge (SS) and wood chips mixtures (WC) treated by combined
      composting and vermicomposting. SSDB added to the mixture before composting
      resulted in significantly higher reproduction rate: on week 4 the number of
      cocoons increased by 213% when compared to the mixture with no biochar. On week 6
      the average number of juveniles increased 11-fold in the mixture with biochar
      added before composting and 5-fold in the mixtures with biochar added after
      composting when compared to the mixture with no biochar. Biochar added before
      composting reduced bioavailability of Cd and Zn to E. fetida. The biochar-added
      vermicomposts showed good fertilizing properties except for elevated
      concentrations of Cr. The pH of all vermicomposts was in the range of 5.27-5.61.
      The obtained vermicomposts can be used as a growing medium for horticultural
      purposes or as an amendment in calcareous soils.

PMID- 27894040
TI  - Plausible exploitation of Jatropha de-oiled seed cake for lipase and phytase
      production and simultaneous detoxification by Candida parapsilosis isolated from
      poultry garbage.
AB  - Jatropha de-oiled seed cake was explored to utilize as a basic nutrient source
      for Candida parapsilosis, isolated from poultry garbage and selected based on the
      production of lipase and phytase enzymes under submerged fermentation. At
      optimized parameters under solid-state fermentation, lipase and phytase
      activities were recorded as 1056.66+/-2.92 and 833+/-2.5U/g of substrate (U/g),
      respectively. Besides enzyme production, complete elimination of phorbol esters
      and significant phytate reduction from 6.51+/-0.01 to 0.43+/-0.01g/100g of seed
      cake were noted after 3days incubation. Curcin and trypsin inhibition activity
      were reduced significantly from 26.33+/-0.43 to 0.56+/-0.02mg/100g and 229.33+/
      2.02 to 11.66+/-0.28U/g, respectively after 5days incubation. Saponins were
      reduced from 5.56+/-0.19 to 1.95+/-0.01g/100g of seed cake after 7days
      incubation.

PMID- 27894041
TI  - Valorization of exhausted sugar beet cossettes by successive hydrolysis and two
      fermentations for the production of bio-products.
AB  - Exhausted sugar beet cossettes (ESBC) show an enormous potential as a source of
      sugars for the production of bio-products. Enzyme hydrolysis with the combined
      effect of mainly cellulases, xylanases and pectinases, turned out to be very
      efficient, obtaining almost double the concentration of sugars measured with the
      sole action of Celluclast(r) and beta-glucosidase, and increasing 5 times the
      hydrolysis rate. As the sole pretreatment, ESBC soaked in the hydrolysis buffer
      were autoclaved, avoiding the application of severe conventional biomass
      pretreatments. Moreover, a promising alternative for the complete utilization of
      glucose, xylose, arabinose, mannose and maltose contained in ESBC is proposed in
      this paper. It consists of sequential fermentation of sugars released in the
      hydrolysis step to produce bioethanol and lactic acid as main bio-products.
      Compared to separate fermentations, with this strategy glucose and hemicellulose
      derived sugars were completely consumed and the 44% of pectin derived sugars.

PMID- 27894043
TI  - Treatment seeking in cannabis dependence: The role of social cognition.
AB  - BACKGROUND AND AIMS: Relatively few cannabis dependent individuals seek treatment
      and little is known about the determinants of treatment seeking. Social Cognitive
      Theory (SCT) provides a useful framework for examining human behaviour and
      motivation which may be helpful in explaining treatment seeking. This study
      examined the differences in cannabis outcome expectancies and cannabis refusal
      self-efficacy between treatment seekers and non-treatment seekers with cannabis
      dependence. DESIGN: Non-treatment seekers were referred to an illicit drug
      diversion program. Treatment seekers commenced an outpatient cannabis treatment
      program and completed a comprehensive assessment that included measures of
      cannabis outcome expectancies and refusal self-efficacy. SETTING: A public
      hospital alcohol and drug outpatient clinic. PARTICIPANTS: 269 non-treatment
      seekers and 195 individuals commencing cannabis dependence treatment.
      MEASUREMENTS: The Cannabis Expectancy Questionnaire (CEQ), Cannabis Refusal Self
      Efficacy Questionnaire (CRSEQ), Severity of Dependence Scale - Cannabis (SDS-C),
      General Health Questionnaire (GHQ-28) and Readiness to Change Questionnaire (RTC)
      were completed. FINDINGS: Treatment seekers had significantly higher levels of
      negative cannabis outcome expectancies and significantly lower levels of
      emotional relief refusal self-efficacy (belief in ability to resist using
      cannabis when experiencing negative affect) (ps<0.001). Treatment seekers had
      significantly higher levels of psychological distress and self-perceived cannabis
      dependence compared to non-treatment seekers (ps<0.001). CONCLUSIONS: High
      negative cannabis outcome expectancies and low emotional relief refusal self
      efficacy may play a key role in motivation to seek treatment.

PMID- 27894042
TI  - Investigation of co-combustion characteristics of sewage sludge and coffee
      grounds mixtures using thermogravimetric analysis coupled to artificial neural
      networks modeling.
AB  - Artificial neural network (ANN) modeling was applied to thermal data obtained by
      non-isothermal thermogravimetric analysis (TGA) from room temperature to 1000
      degrees C at three different heating rates in air to predict the TG curves of
      sewage sludge (SS) and coffee grounds (CG) mixtures. A good agreement between
      experimental and predicted data verified the accuracy of the ANN approach. The
      results of co-combustion showed that there were interactions between SS and CG,
      and the impacts were mostly positive. With the addition of CG, the mass loss rate
      and the reactivity of SS were increased while charring was reduced. Measured
      activation energies (Ea) determined by the Kissinger-Akahira-Sunose (KAS) and
      Ozawa-Flynn-Wall (OFW) methods deviated by <5%. The average value of Ea
      (166.8kJ/mol by KAS and 168.8kJ/mol by OFW, respectively) was the lowest when the
      fraction of CG in the mixture was 40%.

PMID- 27894044
TI  - An insight on synthetic and medicinal aspects of pyrazolo[1,5-a]pyrimidine
      scaffold.
AB  - Pyrazolo[1,5-a]pyrimidine scaffold is one of the privileged hetrocycles in drug
      discovery. Its application as a buliding block for developing drug-like
      candidates has displayed broad range of medicinal properties such as anticancer,
      CNS agents, anti-infectious, anti-inflammatory, CRF1 antagonists and radio
      diagnostics. The structure-activity relationship (SAR) studies have acquired
      greater attention amid medicinal chemists, and many of the lead compounds were
      derived for various disease targets. However, there is plenty of room for the
      medicinal chemists to further exploit this privileged scaffold in developing
      potential drug candidates. The present review briefly outlines relevant synthetic
      strategies employed for pyrazolo[1,5-a]pyrimidine derivatives. It also
      extensively reveals significant biological properties along with SAR studies. To
      the best of our understanding current review is the first attempt made towards
      the compilation of significant advances made on pyrazolo[1,5-a]pyrimidines
      reported since 1980s.

PMID- 27894045
TI  - Scintillation imaging of tritium radioactivity distribution during tritiated
      thymidine uptake by PC12 cells using a melt-on scintillator.
AB  - A scintillation image of tritium fixed in a melt-on scintillator was obtained
      using a charged-coupled device (CCD) imager, and a linear relationship was
      observed between the intensity of the scintillation image and the radioactivity
      of tritium. In a [3H]thymidine uptake experiment, a linear correlation between
      the intensity of the CCD image and the dilution ratio of cells was confirmed.
      Scintillation imaging has the potential for use in direct observation of tritium
      radioactivity distribution.

PMID- 27894046
TI  - Characteristic of thoron (220Rn) in environment.
AB  - This paper describes importance of 220Rn (hereafter thoron) progeny measurement
      for the dose estimation. Although the spatial distribution of thoron activity
      concentration strongly depends on the distance from wall surface as an indoor
      thoron source), a homogeneous distribution was expected to be observed for 212Pb
      activity concentration which was one of thoron progeny. Furthermore, the mean
      equilibrium factor for thoron obtained by the recent measurements in several
      countries widely ranged from 0.008 to 0.07. Therefore the bronchial dose
      evaluated using the equilibrium factor and activity concentration of thoron
      instead of thoron progeny activity concentration may have a large uncertainty.
      Thus, the thoron progeny measurement should be investigated at each measurement
      point for the dose estimation for thoron.

PMID- 27894047
TI  - Predicting the occurrence of wildfires with binary structured additive regression
      models.
AB  - Wildfires are one of the main environmental problems facing societies today, and
      in the case of Galicia (north-west Spain), they are the main cause of forest
      destruction. This paper used binary structured additive regression (STAR) for
      modelling the occurrence of wildfires in Galicia. Binary STAR models are a recent
      contribution to the classical logistic regression and binary generalized additive
      models. Their main advantage lies in their flexibility for modelling non-linear
      effects, while simultaneously incorporating spatial and temporal variables
      directly, thereby making it possible to reveal possible relationships among the
      variables considered. The results showed that the occurrence of wildfires depends
      on many covariates which display variable behaviour across space and time, and
      which largely determine the likelihood of ignition of a fire. The joint
      possibility of working on spatial scales with a resolution of 1 * 1 km cells and
      mapping predictions in a colour range makes STAR models a useful tool for
      plotting and predicting wildfire occurrence. Lastly, it will facilitate the
      development of fire behaviour models, which can be invaluable when it comes to
      drawing up fire-prevention and firefighting plans.

PMID- 27894048
TI  - Real world patterns of care in HER2-overexpressing breast cancer: Results of a
      survey of TEACH clinical trial investigators in 2011.
AB  - BACKGROUND: HER2-overexpressing breast cancer (BC) is common among young patients
      and poses a public health burden. Adjuvant anti-HER2/neu therapy with trastuzumab
      reduces the risk of recurrence and improves survival. METHODS: A web-based survey
      was sent to 386 physicians of the "TEACH" trial in 2011 to determine access to
      HER2/neu testing and treatment patterns for HER2-overexpressing BC. RESULTS:
      There were 151 responders (39%) from 28 countries. Ninety-seven percent reported
      HER2/neu expression is routinely measured in their institutions by
      immunohistochemistry (85%), FISH (80%) and other methods (16%). Twenty percent of
      responders from Asia reported that the test was not routinely available. Forty
      eight percent of participants reported instances when adjuvant HER2-directed
      therapy was recommended to a patient who eventually did not receive it. Reasons
      for not receiving trastuzumab was cost (73%, p < 0.0001) in low- and middle
      income countries and co-morbidities in high-income countries (43%, p = 0.003).
      CONCLUSIONS: This survey reflects the availability of HER2/neu testing and anti
      HER2/neu therapy among physicians who participated in TEACH. A high proportion of
      women with HER2-overexpressing BC may not receive standard adjuvant therapy due
      to unavailability of the test and cost of therapy. Despite having some
      limitations, such as a possible selection bias of participating physicians,
      variable definitions of access to healthcare among respondents, and changes in
      trastuzumab availability since 2011, our results demonstrate that access to care
      and region of practice impact the implementation of cancer treatments.

PMID- 27894049
TI  - Effect of co-doping of sodium on the thermoluminescence dosimetry properties of
      copper-doped zinc lithium borate glass system.
AB  - The effect of sodium as a co-dopant on the thermoluminescence (TL) properties of
      copper-doped zinc lithium borate (ZLB: Cu) subjected to Co-60 gamma radiation is
      reported in this study. TL intensity is enhanced with the introduction of sodium
      in ZLB: Cu. The obtained glow curve is simple with a single peak. The annealing
      procedure and the best heating rate for the proposed thermoluminescent dosimeter
      (TLD) are established, and the phosphor is reusable. The TL response within the
      dose range of 0.5-1000Gy is investigated. The results show that the thermal
      fading behaviour is improved significantly.

PMID- 27894050
TI  - Successful application of a neutral organic base, 1,8
      bis(tetramethylguanidino)naphthalene (TMGN), for the radiosynthesis of
      [11C]raclopride.
AB  - [11C]Raclopride is one of the most popular PET tracers used in Parkinson's
      disease studies. We previously prepared [11C]raclopride with reasonable yields
      using NaOH as an inorganic base, but the reaction patterns fluctuated. In this
      study, we describe the successful application of a commercially available 'super
      basic' proton sponge, TMGN, as a base for the [11C]methylation step using
      [11C]CH3OTf. This novel TMGN method produced better radiochemical yields, as well
      as enhanced reproducibility and a reduction in side products. Under optimal
      conditions (1.2 equiv. of TMGN), the radiochemical yield was 14.4+/-0.2% (ndc,
      EOS, n=5) and the specific activity was 66.6+/-13.3 GBq/mmol (n=5).

PMID- 27894051
TI  - The influence of Sr on the microstructure, degradation and stress corrosion
      cracking of the Mg alloys - ZK40xSr.
AB  - In the present work, new magnesium (Mg) alloys (Mg-4Zn-0.6Zr-xSr, x=0, 0.4, 0.8,
      1.2, 1.6wt%; ZK40xSr) were prepared and studied as potential biodegradable
      materials. The influence of strontium (Sr) addition on the properties of the new
      Mg alloys was investigated, which included microstructure, corrosion degradation,
      and the stress corrosion cracking (SCC) susceptibility. The average grain size of
      the ZK40Sr was approximately 100um, which was significantly smaller than that of
      ZK40 alloy without Sr (402.3+/-40.2um). The size of grain boundaries precipitates
      in the ZK40xSr alloys gradually increased with the increase of Sr content. The
      grain boundaries finally showed a continuously distribution and net-like shape.
      The degradation test showed that the average degradation rate of the ZK40xSr
      alloys increased with the increase of Sr addition. In the case of Mg-4Zn-0.6Zr,
      the degradation rate was 2.2mgcm-2day-1, which was lower than that of Mg-4Zn
      0.6Zr-1.6Sr (4.93mgcm-2day-1). When the ZK40xSr alloys were immersed in m-SBF,
      the rod-like Sr-contained hydroxyapatite (HA) substance was detected, which was
      known to enhance cell growth around bone implants. The fracture surfaces of the
      as-cast Mg-4Zn-0.6Zr-1.6Sr were shown intergranular stress corrosion cracking
      (IGSCC) patterns. The increase of SCC susceptibility of the higher Sr ZK40xSr
      alloys was attributed to the increase of micro-galvanic corrosion between the
      alpha-Mg and the grain boundaries precipitates. The SCC susceptibility values
      were ~0.13 and ~0.41 for the Mg-4Zn-0.6Zr-0.4Sr and the Mg-4Zn-0.6Zr-1.6Sr,
      respectively.

PMID- 27894053
TI  - Ear-like poly (acrylic acid)-activated carbon nanocomposite: A highly efficient
      adsorbent for removal of Cd(II) from aqueous solutions.
AB  - Poly (acrylic acid) modified activated carbon nanocomposite (PAA-AC) was
      synthesized. The structure and morphology of this nanocomposite were
      characterized by FTIR, SEM, TEM, XRD and Zeta potential. The adsorption of some
      heavy metal ions on PAA-AC was studied. The characterization results indicated
      that PAA-AC was a novel and ear-like nanosheet material with the thickness of
      about 40 nm and the diameter of about 300 nm. The adsorption results exhibited
      that the introduction of carboxyl groups into activated carbon evidently
      increased the uptake for heavy metal ions and the nanocomposite had maximum
      uptake for Cd(II). Various variables affecting adsorption of PAA-AC for Cd(II)
      were systematically explored. The maximum capacity and equilibrium time for
      adsorption of Cd(II) by PAA-AC were 473.2 mg g-1 and 15 min. Moreover, the
      removal of Cd(II) for real electroplating wastewater by PAA-AC could reach 98.5%.
      These meant that the removal of Cd(II) by PAA-AC was highly efficient and fast.
      The sorption kinetics and isotherm fitted well with the pseudo-second-order model
      and Langmuir model, respectively. The adsorption mainly was a chemical process by
      chelation. Thermodynamic studies revealed that the adsorption was a spontaneous
      and endothermic process. The results revealed that PAA-AC could be considered as
      a potential candidate for Cd(II) removal.

PMID- 27894052
TI  - Characterization and reactivity of iron based nanoparticles synthesized by tea
      extracts under various atmospheres.
AB  - Bio-synthesis of Fe NPs in inert (nitrogen N-Fe NPs) and oxygen (O-Fe NPs)
      atmospheres employing green tea extracts was investigated through SEM, EDS, XPS
      and FT-IR techniques. The particle sizes of N-Fe NPs and O-Fe NPs were confirmed
      by SEM showing 84.7 +/- 11.5 nm and 117.8 +/- 26.2 nm respectively with
      subsequent evaluation of the percentage composition of Fe and O by EDS. The XPS
      results showed that the zero-valent iron and iron oxide nanoparticles were found
      to be dominant synthesized respectively in nitrogen and oxygen atmospheres. The
      FT-IR spectra further demonstrated that the surface functional groups of Fe NPs
      were different by varying the synthesis atmosphere. Fe NPs were used to remove
      methylene blue (MB) to test the reactivity, and the removal efficiency of MB
      using N-Fe NPs was 98.7%, while that of O-Fe NPs was only 65.3%. Thus it is
      clearly demonstrated that the synthesis atmosphere has prominent effects on the
      formation and catalytic properties of Fe NPs.

PMID- 27894054
TI  - Immunolocalization of metallothionein in hepatocytes of guppy fish (Poecilia
      reticulata) exposed to tannery effluent: A biomarker study.
AB  - Composite tannery effluent (TE) contaminated with a load of metals, especially
      chromium, is used in East Calcutta Wetland Ecosystem (ECW; a Ramsar site of West
      Bengal; No 1208) after natural stabilization for pisciculture and agriculture.
      Quantity and synergistic and antagonistic activities of both essential and
      nonessential metals in the effluents can induce a variety of complex changes in
      animal physiology. High fish yield and no apparent adverse influence on the fish
      biosystems thriving under pollutant stress at ECW allowed the practice to thrive
      sustainably over the last nearly 100 years. Thus, the present study was conducted
      to investigate the role of metallothionein (MT) as a potential biomarker in a
      fish biosystem following acute and chronic exposure to sublethal concentrations
      of tannery wastewater. MT localization in the liver tissue of guppy fish
      (Poecilia reticulata) was studied by the immuno gold-labeled electron microscopic
      technique. The data demonstrated increased metal content in fish body upon
      exposure to TE. Electron micrographs showed significant induction of hepatic MT
      in exposed P. reticulata over control specimens. Liver, being the detoxification
      site of an organism, plays a crucial role in the synthesis of MT and arrest of
      excess metal. The method employed in the present study for demonstrating the
      induction and localization of MT is innovative and could be used as a biomarker
      in fish exposed to metal stress. Our study also indicated that the metalloprotein
      complexes in fish tissue sequestered excess load of metals and thereby arrested
      unwanted interferences of excess metal loads in metabolic processes.

PMID- 27894055
TI  - Indirect effects of climate changes on cadmium bioavailability and biological
      effects in the Mediterranean mussel Mytilus galloprovincialis.
AB  - Despite the great interest in the consequences of climate change on the
      physiological functioning of marine organisms, indirect and interactive effects
      of rising temperature and pCO2 on bioaccumulation and responsiveness to
      environmental pollutants are still poorly explored, particularly in terms of
      cellular mechanisms. According to future projections of temperature and pH/pCO2,
      this study investigated the main cellular pathways involved in metal
      detoxification and oxidative homeostasis in Mediterranean mussels, Mytilus
      galloprovincialis, exposed for 4 weeks to various combinations of two levels of
      pH/pCO2 (8.2/~400 MUatm and 7.4/~3000 MUatm), temperature (20 and 25  degrees C),
      and cadmium addition (0 and 20 MUg/L). Bioaccumulation was increased in metal
      exposed organisms but it was not further modulated by different temperature and
      pH/pCO2 combinations. However, interactions between temperature, pH and cadmium
      had significant effects on induction of metallothioneins, responses of the
      antioxidant system and the onset of oxidative damages, which was tissue
      dependent. Multiple stressors increased metallothioneins concentrations in the
      digestive gland revealing different oxidative effects: while temperature and
      cadmium enhanced glutathione-dependent antioxidant protection and capability to
      neutralize peroxyl radicals, the metal increased the accumulation of lipid
      peroxidation products under acidified conditions. Gills did not reveal specific
      effects for different combinations of factors, but a general stress condition was
      observed in this tissue after various treatments. Significant variations of
      immune system were mainly caused by increased temperature and low pH, while co
      exposure to acidification and cadmium enhanced metal genotoxicity and the onset
      of permanent DNA damage in haemocytes. Elaboration of the whole biomarker data in
      a cellular hazard index, corroborated the synergistic effects of temperature and
      acidification which increased the toxicological effects of cadmium. The overall
      results confirmed that climate change could influence ecotoxicological effects of
      environmental contaminants, highlighting the importance of a better knowledge of
      cellular mechanisms to understand and predict responsiveness of marine organisms
      to such multiple stressors.

PMID- 27894056
TI  - Traditional and new POPs in environments along the Bohai and Yellow Seas: An
      overview of China and South Korea.
AB  - Rapid economic growth during the past two decades in the region surrounding the
      Bohai and Yellow Seas has resulted in severe pollution. Large amounts of
      monitoring data on persistent organic pollutants (POPs) in various environmental
      media have been accumulated, which allows us to conduct a fairly comprehensive
      assessment of the region around the Bohai and Yellow Seas to elucidate spatial
      patterns of pollution on a regional scale. This review summarized distributions
      of traditional and new POPs, including organochlorine pesticides (OCPs),
      polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs),
      hexabromocyclododecanes (HBCDs), and perfluoroalkyl substances (PFASs), in
      various environmental media. In general, due to their physico-chemical properties
      (poor solubility in water), OCPs and PCBs were mainly detected in sediments,
      PBDEs and HBCDs were mainly detected in sediments and soils. PFASs, which have
      greater solubility, were mainly detected in the hydrosphere. For conventional
      POPs, such as OCPs and PCBs, Bohai Bay and Haihe River in China, Gyeonggi Bay and
      Lake Sihwa in South Korea were found to be most polluted areas. While for new
      POPs, such as PBDEs, HBCDs and PFASs, some areas were heavily polluted due to
      local production and applications. Estuarine and coastal areas of the Bohai Sea
      were more severely contaminated by POPs than coastal regions of the Yellow Sea.
      Overall, the present review will guide identification of key areas for
      strengthening risk assessment of POPs and management practices.

PMID- 27894057
TI  - Factors influencing the occurrence and distribution of neonicotinoid insecticides
      in surface waters of southern Ontario, Canada.
AB  - The widespread use of neonicotinoid insecticides and recent increased regulatory
      scrutiny requires the generation of monitoring data with sufficient scope and
      resolution to provide decision makers with a better understanding of occurrence
      and distribution in the environment. This study presents a wide-scale
      investigation of neonicotinoid insecticides used across the range of agricultural
      activities from fifteen surface water sites in southern Ontario. Using
      statistical analysis, the correlation of individual compounds with land use was
      investigated, and the relationship between neonicotinoid occurrence and
      hydrologic parameters in calibrated water courses was also assessed. Of the five
      neonicotinoids studied, imidacloprid, clothianidin and thiamethoxam exhibited
      detection rates above 90% at over half the sites sampled over a three year period
      (2012-2014). At two sites in southwestern Ontario, the Canadian Federal
      freshwater guideline value for imidacloprid (230 ng/L) was exceeded in roughly
      75% of the samples collected. For some watersheds, there were correlations
      between the occurrence of neonicotinoids and precipitation and/or stream
      discharge. Some watersheds exhibited seasonal maxima in concentrations of
      neonicotinoids in spring and fall, particularly for those areas where row crop
      agriculture is predominant; these seasonal patterns were absent in some areas
      characterized by a broad range of agricultural activities.

PMID- 27894059
TI  - Left ventricular diastolic dysfunction in patients with ST-elevation myocardial
      infarction following early and late reperfusion by coronary intervention.
AB  - BACKGROUND: This study prospectively assessed the left ventricular (LV) diastolic
      function changes in patients with ST-elevation myocardial infarction (STEMI) and
      determined if the early revascularization of the infarct-related coronary artery
      in acute phase achieve a better recovery of diastolic function than late
      recanalization. METHODS: Forty-five consecutive patients (61.20+/-11.37years, 8
      females) presenting with STEMI and treated with PCI were prospectively enrolled
      in this study. The important inclusion criteria were first acute coronary
      syndrome episode and LV ejection fraction exceeded 45%. The patients were divided
      to two different groups by total ischemia time (TIT): early reperfusion (TIT<6h)
      and late reperfusion group (TIT>=6h). Transthoracic echocardiography were
      performed within the first week after PCI, and data were compared between groups.
      Evaluation of diastolic function was based on integrated assessment of trans
      mitral Doppler flow pattern, tissue Doppler, and color M-mode ECT. RESULTS: A
      normal diastolic filling pattern was seen in only 9 patients, and the other 80%
      patients had abnormal filling patterns: 16 impaired relaxation, 14 pseudonormal,
      and 6 restrictive filling patterns. The e'septal velocity was lower in early
      reperfusion group compared to late reperfusion group (5.52+/-1.67cm/s vs 7.11+/
      2.14cm/s, P<0.05), but no statistical difference was found in E/e' average
      (11.99+/-4.30 vs 9.85+/-3.47, P>0.05). There was also no statistical difference
      for left atrial volume index and mitral annulus propagation velocity between
      groups. CONCLUSIONS: LV diastolic dysfunction was present in most of acute MI
      patients even after successful PCI. It seemed STEMI patients receiving early
      myocardial reperfusion had no better diastolic functions compared with late
      reperfused patients within the acute phase.

PMID- 27894058
TI  - A non-inferiority trial of Prolonged Exposure for posttraumatic stress disorder:
      In person versus home-based telehealth.
AB  - This is the first randomized controlled trial to evaluate non-inferiority of
      Prolonged Exposure (PE) delivered via home-based telehealth (HBT) compared to
      standard in-person (IP) PE. One-hundred thirty two Veterans recruited from a
      Southeastern Veterans Affairs Medical Center and affiliated University who met
      criteria for posttraumatic stress disorder (PTSD) were randomized to receive PE
      via HBT or PE via IP. Results indicated that PE-HBT was non-inferior to PE-IP in
      terms of reducing PTSD scores at post-treatment, 3 and 6 month follow-up.
      However, non-inferiority hypotheses for depression were only supported at 6 month
      follow-up. HBT has great potential to reduce patient burden associated with
      receiving treatment in terms of travel time, travel cost, lost work, and stigma
      without sacrificing efficacy. These findings indicate that telehealth treatment
      delivered directly into patients' homes may dramatically increase the reach of
      this evidence-based therapy for PTSD without diminishing effectiveness.

PMID- 27894060
TI  - Combined use of tissue Doppler imaging and natriuretic peptides as prognostic
      marker in asymptomatic aortic stenosis.
AB  - INTRODUCTION: Tissue Doppler imaging (TDI) and N-terminal-pro-Brain Natriuretic
      Peptide (NT-proBNP) provides useful non-invasive information about left ventricle
      filling pressures and both have demonstrated to be a prognostic marker in some
      valve disease as aortic stenosis (AS). OBJECTIVES: To assess the clinical value
      of combined TDI and NT-proBNP information in asymptomatic AS patients. MATERIAL
      AND METHODS: Prospective study of 350 initially asymptomatic moderate to severe
      AS patients with: Mean aortic valve area 0.8 (0.3) cm2, mean gradient 45(13)
      mmHg, ejection fraction 61 (9) %. Mean age: 74.6 (4.3) years. In all patients
      were determined NT-proBNP in the serum and TDI parameters the lateral mitral
      annulus. We considered clinical event the admission in the hospital due to
      symptoms related to AS (angina, heart failure or syncope) as well as surgical
      treatment or mortality. RESULTS: After a mean follow-up of 29 (10) months, 165
      (47%) patients suffered some clinical event. In order to predict clinical events,
      Bootstrap analysis determined the best cut-point value: E/E' ratio higher than 13
      and NT-proBNP higher than 515pg/mL. E/E' ratio provides more specificity (78.9%
      vs 55.9%) and NT-proBNP provides more sensitivity (76.6% vs 43.7%). Combined use
      of both parameters provides the best prognostic information (sensitivity 75.6%,
      specificity 67.2%, negative predictive value 82.1%, positive predictive value
      57.5%, accuracy 71.4%). CONCLUSION: Combined use of TDI and natriuretic peptides
      information provides incremental prognostic value and is a useful tool to predict
      the prognosis in asymptomatic AS patients.

PMID- 27894061
TI  - Direct bilirubin: A new risk factor of adverse outcome in idiopathic pulmonary
      arterial hypertension.
AB  - BACKGROUND: Previous studies have shown that elevated total bilirubin was
      associated with advanced heart failure, yet no study has ascertained the
      predictive value of direct serum bilirubin (DBIL) in idiopathic pulmonary
      arterial hypertension (IPAH). This study aimed to investigate the predictive
      value of both baseline and follow-up DBIL in patients with IPAH. METHODS: Serum
      DBIL was measured in 404 IPAH patients at enrollment. Almost 92% patients
      received specific drugs after diagnosis confirmed. Serum DBIL was repeated in 237
      patients after a mean of 8.3months treatment. Survival rate among normal DBIL
      group and abnormal DBIL group was compared using the Kaplan-Meier method. The
      prognostic value of baseline variables was tested by Cox regression models.
      RESULTS: During median follow-up period of 40months, 153 patients died. Baseline
      DBIL levels were significantly higher in non-survivors compared with survivors
      (p<0.001). DBIL levels in survivors decreased significantly during PAH therapy,
      whereas there was almost no decrease in non-survivors. Patients with abnormal
      DBIL at baseline or during therapy had a significantly lower survival rates than
      those with normal DBIL group, according to Kaplan-Meier survival analysis
      (p=0.002 and p<0.0001, respectively). According to multivariate analyses,
      baseline DBIL was an independent risk factor of mortality in IPAH. CONCLUSIONS:
      Serum DBIL could predict severity and outcomes of IPAH: in particular, no obvious
      decrease in DBIL during PAH-specific drug therapy is strongly associated with
      worse prognosis in IPAH.

PMID- 27894062
TI  - Echocardiographic comparison between left ventricular non-compaction and
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Modern imaging technology has improved detection of left ventricular
      non-compaction cardiomyopathy (LVNC). Hypertrophic cardiomyopathy (HCM) shares
      morphological features with LVNC, but prognosis and treatment strategies differ
      between LVNC and HCM. METHODS AND RESULTS: We aimed to compare global and
      regional LV myocardial function in LVNC and HCM. We hypothesized that apical
      function is reduced in LVNC due to the embryonic reduced compaction of the apex.
      We studied 25 patients with LVNC (47+/-14years) according to current criteria, 50
      with HCM (47+/-14years) and 50 healthy individuals (49+/-19years). By
      echocardiography, we assessed maximal wall thickness (MWT) and LV ejection
      fraction (EF). Numbers of trabeculations were counted from 3 apical views. Global
      longitudinal strain by speckle tracking echocardiography was calculated from a 16
      LV segments model. LV basal (6 segments) and apical (4 segments) longitudinal
      strains were averaged. MWT was thinner, EF lower and trabeculations were more
      pronounced in LVNC compared to HCM (all p<0.001) but with no significantly
      differences in LV global longitudinal strain (-15.1+/-6.1 vs. -16.8+/-3.7,
      p=0.14). Function by longitudinal strain increased significantly from base to
      apex in HCM (-14.9+/-4.3% vs. -19.5+/-4.7%, p<0.001) and in healthy controls (
      20.0+/-1.9% vs. -21.8+/-2.9%, p<0.001), but not in LVNC (-14.7+/-6.4% vs. -15.7+/
      7.2%, p=0.35). CONCLUSIONS: Increased number of trabeculations, thinner MWT and
      lower EF were characteristics of LVNC. Myocardial function was homogeneously
      reduced in LVNC, while an apical to basal gradient with relatively preserved
      apical function was present in HCM. These characteristics may help to
      discriminate between LVNC and HCM.

PMID- 27894064
TI  - Dietary gossypol suppressed postprandial TOR signaling and elevated ER stress
      pathways in turbot (Scophthalmus maximus L.).
AB  - Gossypol is known to be a polyphenolic compound toxic to animals. However, its
      molecular targets are far from fully characterized. To evaluate the physiological
      and molecular effects of gossypol, we chose turbot (Scophthalmus maximus L.), a
      carnivorous fish, as our model species. Juvenile turbots (7.83 +/- 0.02 g) were
      fed diets containing gradient levels of gossypol at 0 (G0), 600 (G1), and 1,200
      (G2) mg/kg diets for 11 wk. After the feeding trial, fish growth, body protein,
      and fat contents were significantly reduced in the G2 group compared with those
      of the G0 group (P < 0.05). Gossypol had little impact on digestive enzyme
      activities and intestine morphology. However, gossypol caused liver fibrosis and
      stimulated chemokine and proinflammatory cytokine secretions. More importantly,
      gossypol suppressed target of rapamycin (TOR) signaling and induced endoplasmic
      reticulum (ER) stress pathway in both the feeding experiment and cell cultures.
      Our results demonstrated that gossypol inhibited TOR signaling and elevated ER
      stress pathways both in vivo and in vitro, thus providing new mechanism of action
      of gossypol in nutritional physiology.

PMID- 27894063
TI  - Loss of glutaredoxin 3 impedes mammary lobuloalveolar development during
      pregnancy and lactation.
AB  - Mammalian glutaredoxin 3 (Grx3) has been shown to be important for regulating
      cellular redox homeostasis in the cell. Our previous studies indicate that Grx3
      is significantly overexpressed in various human cancers including breast cancer
      and demonstrate that Grx3 controls cancer cell growth and invasion by regulating
      reactive oxygen species (ROS) and NF-kappaB signaling pathways. However, it
      remains to be determined whether Grx3 is required for normal mammary gland
      development and how it contributes to epithelial cell proliferation and
      differentiation in vivo. In the present study, we examined Grx3 expression in
      different cell types within the developing mouse mammary gland (MG) and found
      enhanced expression of Grx3 at pregnancy and lactation stages. To assess the
      physiological role of Grx3 in MG, we generated the mutant mice in which Grx3 was
      deleted specifically in mammary epithelial cells (MECs). Although the reduction
      of Grx3 expression had only minimal effects on mammary ductal development in
      virgin mice, it did reduce alveolar density during pregnancy and lactation. The
      impairment of lobuloalveolar development was associated with high levels of ROS
      accumulation and reduced expression of milk protein genes. In addition,
      proliferative gene expression was significantly suppressed with proliferation
      defects occurring in knockout MECs during alveolar development compared with wild
      type controls. Therefore, our findings suggest that Grx3 is a key regulator of
      ROS in vivo and is involved in pregnancy-dependent mammary gland development and
      secretory activation through modulating cellular ROS.

PMID- 27894067
TI  - Quenching the thirst for hunger.

PMID- 27894065
TI  - Evaluation of CSF and plasma biomarkers of brain melanocortin activity in
      response to caloric restriction in humans.
AB  - The melanocortin neuronal system, which consists of hypothalamic
      proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, is a leptin
      target that regulates energy balance and metabolism, but studies in humans are
      limited by a lack of reliable biomarkers to assess brain melanocortin activity.
      The objective of this study was to measure the POMC prohormone and its processed
      peptide, beta-endorphin (beta-EP), in cerebrospinal fluid (CSF) and AgRP in CSF
      and plasma after calorie restriction to validate their utility as biomarkers of
      brain melanocortin activity. CSF and plasma were obtained from 10 lean and obese
      subjects after fasting (40 h) and refeeding (24 h), and from 8 obese subjects
      before and after 6 wk of dieting (800 kcal/day) to assess changes in neuropeptide
      and hormone levels. After fasting, plasma leptin decreased to 35%, and AgRP
      increased to 153% of baseline. During refeeding, AgRP declined as leptin
      increased; CSF beta-EP increased, but POMC did not change. Relative changes in
      plasma and CSF leptin were blunted in obese subjects. After dieting, plasma and
      CSF leptin decreased to 46% and 70% of baseline, CSF POMC and beta-EP decreased,
      and plasma AgRP increased. At baseline, AgRP correlated negatively with insulin
      and homeostasis model assessment (HOMA-IR), and positively with the Matsuda
      index. Thus, following chronic calorie restriction, POMC and beta-EP declined in
      CSF, whereas acutely, only beta-EP changed. Plasma AgRP, however, increased after
      both acute and chronic calorie restriction. These results support the use of CSF
      POMC and plasma AgRP as biomarkers of hypothalamic melanocortin activity and
      provide evidence linking AgRP to insulin sensitivity.

PMID- 27894066
TI  - Obesity-associated extracellular mtDNA activates central TGFbeta pathway to cause
      blood pressure increase.
AB  - Hypothalamic inflammation was recently found to mediate obesity-related
      hypertension, but the responsible upstream mediators remain unexplored. In this
      study, we show that dietary obesity is associated with extracellular release of
      mitochondrial DNA (mtDNA) into the cerebrospinal fluid and that central delivery
      of mtDNA mimics transforming growth factor-beta (TGFbeta) excess to activate
      downstream signaling pathways. Physiological study reveals that central
      administration of mtDNA or TGFbeta is sufficient to cause hypertension in mice.
      Knockout of the TGFbeta receptor in proopiomelanocortin neurons counteracts the
      hypertensive effect of not only TGFbeta but also mtDNA excess, while the
      hypertensive action of central mtDNA can be blocked pharmacologically by a
      TGFbeta receptor antagonist or genetically by TGFbeta receptor knockout. Finally,
      we confirm that obesity-induced hypertension can be reversed through central
      treatment with TGFbeta receptor antagonist. In conclusion, circulating mtDNA in
      the brain employs neural TGFbeta pathway to mediate a central inflammatory
      mechanism of obesity-related hypertension.

PMID- 27894069
TI  - Association Between Left Atrial Dilatation and Invasive Hemodynamics at Rest and
      During Exercise in Asymptomatic Aortic Stenosis.
AB  - BACKGROUND: Transition from an asymptomatic to symptomatic state in severe aortic
      stenosis is often difficult to assess. Identification of a morphological sign of
      increased hemodynamic load may be important in asymptomatic aortic stenosis to
      identify patients at risk. METHODS AND RESULTS: Thirty-nine patients with
      asymptomatic severe aortic stenosis (aortic valve area <1 cm2, peak jet velocity
      >3.5 m/s) underwent exercise testing with simultaneous invasive hemodynamic
      monitoring and Doppler echocardiography. Cardiac index, pulmonary artery
      pressure, and pulmonary capillary wedge pressure (PCWP) were recorded. Patients
      were followed up for the composite end point of death, unplanned hospitalization,
      or aortic valve replacement. Patients were stratified into 2 groups according to
      left atrial (LA) volume index >=35 mL/m2. In 25 patients (64%) LA volume index
      was >=35 mL/m2. Aortic valve area was similar between groups (0.81+/-0.15 versus
      0.84+/-0.18 cm2; P=0.58). PCWP was higher at rest and during exercise in patients
      with LA volume index >=35 mL/m2 (P<0.01), despite similar cardiac index. At rest,
      PCWP was <12 mm Hg in 11 patients (44%) with LA dilatation, whereas PCWP was <25
      mm Hg in 1 patient (4%) with exercise. LA volume index and E/e' predicted
      exercise PCWP>30 mm Hg with areas under the receiver operating curve of 0.75 and
      0.84, respectively. During follow-up, 14 cardiac events were recorded. LA volume
      was associated with a hazard ratio of 1.90 (95% confidence interval, 0.92-4.15).
      CONCLUSIONS: LA size reflects hemodynamic burden in patients with asymptomatic
      severe aortic stenosis. Quantitative measurements of LA and diastolic function
      are associated with left ventricular filling pressures with exercise and could be
      used to identify asymptomatic patients with increased hemodynamic burden.
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT02395107.

PMID- 27894068
TI  - Residual Myocardial Iron Following Intramyocardial Hemorrhage During the
      Convalescent Phase of Reperfused ST-Segment-Elevation Myocardial Infarction and
      Adverse Left Ventricular Remodeling.
AB  - BACKGROUND: The presence of intramyocardial hemorrhage (IMH) in ST-segment
      elevation myocardial infarction patients reperfused by primary percutaneous
      coronary intervention has been associated with residual myocardial iron at follow
      up, and its impact on adverse left ventricular (LV) remodeling is incompletely
      understood and is investigated here. METHODS AND RESULTS: Forty-eight ST-segment
      elevation myocardial infarction patients underwent cardiovascular magnetic
      resonance at 4+/-2 days post primary percutaneous coronary intervention, of whom
      40 had a follow-up scan at 5+/-2 months. Native T1, T2, and T2* maps were
      acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A
      subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had
      IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute
      scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the
      follow-up scan, 13/15 patients (87%) had evidence of residual iron within the
      infarct zone. Patients with residual iron had higher T2 in the infarct zone
      surrounding the residual iron when compared with those without. In patients with
      adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was
      also higher than in those without (60 [54-64] ms versus 53 [51-56] ms; P=0.025).
      Acute myocardial infarct size, extent of microvascular obstruction, and IMH
      correlated with the change in LV end-diastolic volume (Pearson's rho of 0.64,
      0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation
      coefficient comparison) and performed equally well on receiver operating
      characteristic curve for predicting adverse LV remodeling (area under the curve:
      0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic
      curve comparison). CONCLUSIONS: The majority of ST-segment-elevation myocardial
      infarction patients with IMH had residual myocardial iron at follow-up. This was
      associated with persistently elevated T2 values in the surrounding infarct tissue
      and adverse LV remodeling. IMH and residual myocardial iron may be potential
      therapeutic targets for preventing adverse LV remodeling in reperfused ST-segment
      elevation myocardial infarction patients.

PMID- 27894070
TI  - The STRATEGY Study (Stress Cardiac Magnetic Resonance Versus Computed Tomography
      Coronary Angiography for the Management of Symptomatic Revascularized Patients):
      Resources and Outcomes Impact.
AB  - BACKGROUND: Computed tomography coronary angiography (cTCA) and stress cardiac
      magnetic resonance (stress-CMR) are suitable tools for diagnosing obstructive
      coronary artery disease in symptomatic patients with previous history of
      revascularization. However, performance appraisal of noninvasive tests must take
      in account the consequent diagnostic testing, invasive procedures, clinical
      outcomes, radiation exposure, and cumulative costs rather than their diagnostic
      accuracy only. We aimed to compare an anatomic (cTCA) versus a functional (stress
      CMR) strategy in symptomatic patients with previous myocardial revascularization
      procedures. METHODS AND RESULTS: Six hundred patients with chest pain and
      previous revascularization included in a prospective observational registry and
      evaluated by clinically indicated cTCA (n=300, mean age 68.2+/-9.7 years, male
      255) or stress-CMR (n=300, mean age 67.6+/-9.7 years, male 263) were enrolled and
      followed-up in terms of subsequent noninvasive tests, invasive coronary
      angiography, revascularization procedures, cumulative effective radiation dose,
      major adverse cardiac events, defined as a composite end point of nonfatal
      myocardial infarction and cardiac death, and medical costs. The mean follow-up
      for cTCA and stress-CMR groups was similar (773.6+/-345 versus 752.8+/-291 days;
      P=0.21). Compared with stress-CMR, cTCA was associated with a higher rate of
      subsequent noninvasive tests (28% versus 17%; P=0.0009), invasive coronary
      angiography (31% versus 20%; P=0.0009), and revascularization procedures (24%
      versus 16%; P=0.007). Stress-CMR strategy was associated with a significant
      reduction of radiation exposure and cumulative costs (59% and 24%, respectively;
      P<0.001). Finally, patients undergoing stress-CMR showed a lower rate of major
      adverse cardiac events (5% versus 10%; P<0.010) and cost-effectiveness ratio
      (119.98+/-250.92 versus 218.12+/-298.45 Euro/y; P<0.001). CONCLUSIONS: Compared
      with cTCA, stress-CMR is more cost-effective in symptomatic revascularized
      patients.

PMID- 27894071
TI  - The Essence of STRATEGY Is Choosing What Not to Do.

PMID- 27894072
TI  - "Rusty Hearts": Is It Time to Rethink Iron Chelation Therapies in Post-Myocardial
      Infarction Setting?

PMID- 27894073
TI  - C'est LAVi: What Left Atrial Dilatation Tells Us About Diastolic Function in
      Aortic Stenosis.

PMID- 27894074
TI  - LSD1 mediates MYCN control of epithelial-mesenchymal transition through silencing
      of metastatic suppressor NDRG1 gene.
AB  - Neuroblastoma (NB) with MYCN amplification is a highly aggressive and metastatic
      tumor in children. The high recurrence rate and resistance of NB cells to drugs
      urgently demands a better therapy for this disease. We have recently found that
      MYCN interacts with the lysine-specific demethylase 1 (LSD1), a histone modifier
      that participates in key aspects of gene transcription. In cancer cells, LSD1
      contributes to the genetic reprogramming that underlies to Epithelial-Mesenchymal
      Transition (EMT) and tumor metastasis. Here, we show that LSD1 affects motility
      and invasiveness of NB cells by modulating the transcription of the metastasis
      suppressor NDRG1 (N-Myc Downstream-Regulated Gene 1). At mechanistic level, we
      found that LSD1 co-localizes with MYCN at the promoter region of the NDRG1 gene
      and inhibits its expression. Pharmacological inhibition of LSD1 relieves
      repression of NDRG1 by MYCN and affects motility and invasiveness of NB cells.
      These effects were reversed by overexpressing NDRG1. In NB tissues, high levels
      of LSD1 correlate with low levels of NDRG1 and reduced patients survival.
      Collectively, our findings elucidate a mechanism of how MYCN/LSD1 control
      motility and invasiveness of NB cells through transcription regulation of NDRG1
      expression and suggest that pharmacological targeting of LSD1 represents a
      valuable approach for NB therapy.

PMID- 27894076
TI  - Co-expression of Piwil2/Piwil4 in nucleus indicates poor prognosis of
      hepatocellular carcinoma.
AB  - PURPOSE: This study aimed to explore the localization and expression of P-element
      induced wimpy testis-like 2 (piwil2)/Piwil4 in hepatocellular carcinoma (HCC)
      tissues, and analyze the correlation between co-expression pattern and prognosis
      of HCC. RESULTS: Piwil2 showed 100% positive expression in the cell nucleus, with
      the intensity higher than in the cytoplasm. Piwil4 showed a lower intensity of
      expression in the cell nucleus than in the cytoplasm. The molecular chaperone
      Piwil2/Piwil4 had four co-expression patterns: nuclear co-expression, nuclear and
      cytoplasmic co-expression, cytoplasmic co-expression, and non-coexpression. The
      survival rate and the overall survival sequentially increased. The prognostic
      phenotype of the nuclear co-expression of Piwil2/Piwil4 was worse than that of
      non-coexpression, and the intracellular localization and expression of Piwil2 and
      Piwil4 were not significantly different. METHODS: HCC pathological tissue samples
      with follow-up information (90 cases) and 2 normal control liver tissues were
      collected and made into a 92-site microarray. The expression of Piwil2 and Piwil4
      was detected using the immunofluorescence double staining method. The differences
      in the expression and location of Piwil2 and Piwil4 in tumor cells were explored,
      and the influence of such differences on the long-term survival rate of HCC was
      studied using Kaplan-Meier survival curve and log-rank test. The clinical staging
      was analyzed according to the HCC international TNM staging criteria.
      CONCLUSIONS: The nuclear co-expression of Piwil2/Piwil4 indicated that patients
      with HCC had a worse prognostic phenotype. The molecular chaperone Piwil2/Piwil4
      seems promising as a molecular marker for prognosis judgment; a single marker
      (Piwil2/Piwil4) cannot be used for prognosis judgment.

PMID- 27894075
TI  - Mammographic density: a potential monitoring biomarker for adjuvant and
      preventative breast cancer endocrine therapies.
AB  - Increased mammographic density (MD) has been shown beyond doubt to be a marker
      for increased breast cancer risk, though the underpinning pathobiology is yet to
      be fully elucidated. Estrogenic activity exerts a strong influence over MD, which
      consequently has been observed to change predictably in response to tamoxifen
      anti-estrogen therapy, although results for other selective estrogen receptor
      modulators and aromatase inhibitors are less consistent. In both primary and
      secondary prevention settings, tamoxifen-associated MD changes correlate with
      successful modulation of risk or outcome, particularly among pre-menopausal
      women; an observation that supports the potential use of MD change as a surrogate
      marker where short-term MD changes reflect longer-term anti-estrogen efficacy.
      Here we summarize endocrine therapy-induced MD changes and attendant outcomes and
      discuss both the need for outcome surrogates in such therapy, as well as make a
      case for MD as such a monitoring marker. We then discuss the process and steps
      required to validate and introduce MD into practice as a predictor or surrogate
      for endocrine therapy efficacy in preventive and adjuvant breast cancer treatment
      settings.

PMID- 27894077
TI  - Tyrosine kinase fusion genes in pediatric BCR-ABL1-like acute lymphoblastic
      leukemia.
AB  - Approximately 15% of pediatric B cell precursor acute lymphoblastic leukemia (BCP
      ALL) is characterized by gene expression similar to that of BCR-ABL1-positive
      disease and unfavorable prognosis. This BCR-ABL1-like subtype shows a high
      frequency of B-cell development gene aberrations and tyrosine kinase-activating
      lesions. To evaluate the clinical significance of tyrosine kinase gene fusions in
      children with BCP-ALL, we studied the frequency of recently identified tyrosine
      kinase fusions, associated genetic features, and prognosis in a representative
      Dutch/German cohort. We identified 14 tyrosine kinase fusions among 77 BCR-ABL1
      like cases (18%) and none among 76 non-BCR-ABL1-like B-other cases. Novel exon
      fusions were identified for RCSD1-ABL2 and TERF2-JAK2. JAK2 mutation was mutually
      exclusive with tyrosine kinase fusions and only occurred in cases with high CRLF2
      expression. The non/late response rate and levels of minimal residual disease in
      the fusion-positive BCR-ABL1-like group were higher than in the non-BCR-ABL1-like
      B-others (p<0.01), and also higher, albeit not statistically significant,
      compared with the fusion-negative BCR-ABL1-like group. The 8-year cumulative
      incidence of relapse in the fusion-positive BCR-ABL1-like group (35%) was
      comparable with that in the fusion-negative BCR-ABL1-like group (35%), and worse
      than in the non-BCR-ABL1-like B-other group (17%, p=0.07). IKZF1 deletions,
      predominantly other than the dominant-negative isoform and full deletion, co
      occurred with tyrosine kinase fusions. This study shows that tyrosine kinase
      fusion-positive cases are a high-risk subtype of BCP-ALL, which warrants further
      studies with specific kinase inhibitors to improve outcome.

PMID- 27894078
TI  - Overexpression of ANXA3 is an independent prognostic indicator in gastric cancer
      and its depletion suppresses cell proliferation and tumor growth.
AB  - BACKGROUND: Gastric cancer (GC) is one of the most common malignancies worldwide.
      Tumour metastasis is one of the leading causes of death in GC patients. This
      study aims to investigate the significance of ANXA3 expression and the mechanism
      by which ANXA3 is involved in the epithelial-mensenchymal transition (EMT) of
      gastric cancer cells. RESULTS: Our results confirmed that ANXA3 was high
      expression at the mRNA and protein level in GC cancer tissues and the majority of
      GC cell lines. In clinicopathological analysis, we found that increased
      expression of ANXA3 in tumors was closely associated with a poor prognosis.
      Xogenous ANXA3 transduction promoted proliferation, clone formation, migration,
      and invasion. Small interfering RNA silencing of ANXA3 inhibited these processes.
      Silence of ANXA3 inhibited tumorigenicity in vivo. Additionally, ANXA3 expression
      is associated with the epithelial-mesenchymal transition. METHODS: Firstly, we
      investigated the ANXA3 expression on mRNA and protein level with RT-PCR and
      Western blot. Secondly, 183 GC patients tissues were used the to evaluate the
      clinicopathological characteristics and prognosis through immunohistochemistry.
      Furthermore, The functions of ANXA3 were analyzed in the cell proliferation,
      Colony Formation, migration, invasion and apoptosis of GC cell lines.
      CONCLUSIONS: Our research suggests that ANXA3 plays important roles in gastric
      cancer carcinogenesis and metastasis, and provides a valuable prognostic marker
      and potential target for treatment of gastric cancer patients.

PMID- 27894081
TI  - MBD3 inhibits formation of liver cancer stem cells.
AB  - Liver cancer cells can be reprogrammed into induced cancer stem cells (iCSCs) by
      exogenous expression of the reprogramming transcription factors Oct4, Sox2, Klf4
      and c-Myc (OSKM). The nucleosome remodeling and deacetylase (NuRD) complex is
      essential for reprogramming somatic cells. In this study, we investigated the
      function of NuRD in the induction of liver CSCs. We showed that suppression of
      methyl-CpG binding domain protein 3 (MBD3), a core subunit of the NuRD repressor
      complex, together with OSKM transduction, induces conversion of liver cancer
      cells into stem-like cells. Expression of the transcription factor c-JUN is
      increased in MBD3-depleted iCSCs, and c-JUN activates endogenous pluripotent
      genes and regulates iCSC-related genes. These results indicate that MBD3/NuRD
      inhibits the induction of iCSCs, while c-JUN facilitates the generation of CSC
      like properties. The iCSC reprogramming approach devised here provides a novel
      platform for dissection of the disordered signaling in liver CSCs. In addition,
      our results indicate that c-JUN may serve as a potential target for liver cancer
      therapy.

PMID- 27894079
TI  - MicroRNA-214 protects against hypoxia/reoxygenation induced cell damage and
      myocardial ischemia/reperfusion injury via suppression of PTEN and Bim1
      expression.
AB  - BACKGROUND: Myocardial apoptosis plays an important role in myocardial
      ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the
      myocardium from I/R injury. This study investigated the role of miR-214 in
      hypoxia/reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R
      injury in vivo. METHODS AND RESULTS: H9C2 cardiomyoblasts were transfected with
      lentivirus expressing miR-214 (LmiR-214) or lentivirus expressing scrambled miR
      control (LmiR-control) respectively, to establish cell lines of LmiR-214 and LmiR
      control. The cells were subjected to hypoxia for 4 h followed by reoxygenation
      for 24 h. Transfection of LmiR-214 suppresses PTEN expression, significantly
      increases the levels of Akt phosphorylation, markedly attenuates LDH release, and
      enhances the viability of the cells subjected to H/R. In vivo transfection of
      mouse hearts with LmiR-214 significantly attenuates I/R induced cardiac
      dysfunction and reduces I/R-induced myocardial infarct size. LmiR-214
      transfection significantly attenuates I/R-induced myocardial apoptosis and
      caspase-3/7 and caspase-8 activity. Increased expression of miR-214 by
      transfection of LmiR-214 suppresses PTEN expression, increases the levels of
      phosphorylated Akt, represses Bim1 expression and induces Bad phosphorylation in
      the myocardium. In addition, in vitro data shows transfection of miR-214 mimics
      to H9C2 cells suppresses the expression and translocation of Bim1 from cytosol to
      mitochondria and induces Bad phosphorylation. CONCLUSIONS: Our in vitro and in
      vivo data suggests that miR-214 protects cells from H/R induced damage and
      attenuates I/R induced myocardial injury. The mechanisms involve activation of
      PI3K/Akt signaling by targeting PTEN expression, induction of Bad
      phosphorylation, and suppression of Bim1 expression, resulting in decreases in
      I/R-induced myocardial apoptosis.

PMID- 27894080
TI  - Genetic variants in the acylphosphatase 2 gene and the risk of breast cancer in a
      Han Chinese population.
AB  - We performed a case-control study to investigate the associations between seven
      single nucleotide polymorphisms (SNPs) in the acylphosphatase 2 (ACYP2) gene and
      breast cancer (BC) risk in a Han Chinese population. There were 183 BC cases and
      195 healthy controls included in the study. The SNPs were genotyped using the
      Sequenom MassARRAY platform. Logistic regression (adjusted for age group, body
      mass index [BMI], and menopause status), was used to evaluate the associations
      between the various genotypes and BC risk. Statistical analysis revealed that
      rs12621038 was associated with a decreased risk of BC in the allele (T vs. C:
      odds ratio [OR] = 0.71, 95% confidence interval [95% CI] = 0.52-0.94; p = 0.016),
      homozygous (TT vs. CC: OR = 0.47, 95% CI = 0.24-0.85; p = 0.014), dominant (OR =
      0.62; 95% CI = 0.40-0.96; p = 0.032), and additive (OR = 0.68; 95% CI = 0.50
      0.92; p = 0.012) models. In addition, we found that rs1682111 and rs17045754 were
      associated with the risk of BC and correlated with recurrence, and that rs6713088
      correlated with tumor size. In sum, our findings reveal significant associations
      between SNPs in the ACYP2 gene and BC risk in a Han Chinese population.

PMID- 27894082
TI  - The disintegrin echistatin in combination with doxorubicin targets high
      metastatic human osteosarcoma overexpressing alphanubeta3 integrin in chick
      embryo and nude mouse models.
AB  - Echistatin, a cyclic RGD peptide, which is an antagonist of alphavbeta3 integrin
      (disintegrin), inhibited human osteosarcoma in the chick chorioallontoic membrane
      (CAM) model and tumor growth and pulmonary metastases in a nude mouse orthotopic
      model. A high-metastatic variant of human osteosarcoma, 143B-LM4, overexpressing
      alphavbeta3 integrin was used. Tumor angiogenesis by high-metastatic variant 143B
      LM4 cells in the CAM was significantly inhibited by echistatin (P<0.05) as was
      overall growth. A doxorubicin (DOX)-echistatin combination inhibited orthotopic
      tumor growth compared to untreated control (P<0.01) or DOX alone (P<0.05) in nude
      mice. Tumor-bearing mice treated with the DOX-echistatin combination survived
      longer than those treated with DOX alone or control PBS (P<0.01 and P<0.01,
      respectively). Echistatin also inhibited experimental lung metastasis of 143B-LM4
      cells in nude mice. These results suggest that DOX in combination with a
      disintegrin has potential to treat osteosarcoma and that alphavbeta3 integrin may
      be a target for osteosarcoma.

PMID- 27894083
TI  - Suppression of Nestin reveals a critical role for p38-EGFR pathway in neural
      progenitor cell proliferation.
AB  - The expression of intermediate filament Nestin is necessary for the neural
      progenitor cells (NPCs) to maintain stemness, but the underlying cellular and
      molecular mechanism remains unclear. In this study, we demonstrated that Nestin
      is required for the self-renew of NPCs through activating MAPK and EGFR pathways.
      Knockdown of Nestin by shRNA inhibited cell cycle progression and proliferation
      in mouse NPCs. Moreover, suppression of Nestin reduced expression of the
      epidermal growth factor receptor (EGFR) in NPCs and inhibited the mitogenic
      effects of EGF on these cells. Treatment of NPCs with p38-MAPK inhibitor PD169316
      reversed cell cycle arrest caused by the knockdown of Nestin. Our findings
      indicate that Nestin promotes NPC proliferation via p38-MAPK and EGFR pathways,
      and reveals the necessity of these pathways in NPCs self-renewal.

PMID- 27894084
TI  - Curcumin increases exosomal TCF21 thus suppressing exosome-induced lung cancer.
AB  - Curcumin is a novel drug for lung cancer treatment. However, the mechanism
      underlying the anti-tumor effect of curcumin remains elusive. Previous evidences
      indicated that, the methylating transferase DNMT1 is downregulated by curcumin,
      and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt
      to elucidate the correlation between curcumin treatment and TCF21 expression.
      Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B
      cells, which induced proliferation, colony formation and migration of BEAS-2B
      cells. An increase in TCF21 expression in response to curcumin was also seen, as
      revealed by real-time PCR (RT-PCR) and western blot. Analysis using the GEO
      database (access #GSE21210) indicated that a positive correlation existed between
      TCF21 levels and lung cancer patient survival. TCF21 overexpression and knockdown
      was introduced to H1299 cells through lentiviral system, which led to suppression
      and promotion of tumor growth, respectively. We also demonstrated that DNMT1
      expression was downregulated by curcumin. Therefore, curcumin exerts its anti
      cancer function by downregulating DNMT1, thereby upregulating TCF21.

PMID- 27894085
TI  - Tracing anti-cancer and cancer-promoting actions of all-trans retinoic acid in
      breast cancer to a RARalpha epigenetic mechanism of mammary epithelial cell fate.
AB  - A hallmark of cancer cells is the ability to evade the growth inhibitory/pro
      apoptotic action of physiological all-trans retinoic acid (RA) signal, the
      bioactive derivative of Vitamin A. However, as we and others reported, RA can
      also promote cancer cell growth and invasion. Here we show that anticancer and
      cancer-promoting RA actions in breast cancer have roots in a mechanism of mammary
      epithelial cell morphogenesis that involves both transcriptional (epigenetic) and
      non-transcriptional RARalpha (RARA) functions. We found that the mammary
      epithelial cell-context specific degree of functionality of the RARA
      transcriptional (epigenetic) component of this mechanism, by tuning the effects
      of the non-transcriptional RARA component, determines different cell fate
      decisions during mammary morphogenesis. Indeed, factors that hamper the RARA
      epigenetic function make physiological RA drive aberrant morphogenesis via non
      transcriptional RARA, thus leading to cell transformation. Remarkably, also the
      cell context-specific degree of functionality of the RARA epigenetic component
      retained by breast cancer cells is critical to determine cell fate decisions in
      response to physiological as well as supraphysiological RA variation. Overall
      this study supports the proof of principle that the epigenetic functional
      plasticity of the mammary epithelial cell RARA mechanism, which is essential for
      normal morphogenetic processes, is necessary to deter breast cancer
      onset/progression consequent to the insidious action of physiological RA.

PMID- 27894087
TI  - Negative feedback between TAp63 and Mir-133b mediates colorectal cancer
      suppression.
AB  - BACKGROUND: TAp63 is known as the most potent transcription activator and tumor
      suppressor. microRNAs (miRNAs) are increasingly recognized as essential
      components of the p63 pathway, mediating downstream post-transcriptional gene
      repression. The aim of present study was to investigate a negative feedback loop
      between TAp63 and miR-133b. RESULTS: Overexpression of TAp63 inhibited HCT-116
      cell proliferation, apoptosis and invasion via miR-133b. Accordingly, miR-133b
      inhibited TAp63 expression through RhoA and its downstream pathways. Moreover, we
      demonstrated that TAp63/miR-133b could inhibit colorectal cancer proliferation
      and metastasis in vivo and vitro. MATERIALS AND METHODS: We evaluated the
      correlation between TAp63 and miR-133b in HCT-116 cells and investigated the
      roles of the TAp63/miR-133b feedback loop in cell proliferation, apoptosis and
      metastasis via MTT, flow cytometry, Transwell, and nude mouse xenograft
      experiments. The expression of TAp63, miR-133b, RhoA, alpha-tubulin and Akt was
      assessed via qRT-PCR, western blot and immunofluorescence analyses. miR-133b
      target genes were identified through luciferase reporter assays. CONCLUSIONS: miR
      133b plays an important role in the anti-tumor effects of TAp63 in colorectal
      cancer. miR-133b may represent a tiemolecule between TAp63 and RhoA, forming a
      TAp63/miR-133b/RhoA negative feedback loop, which could significantly inhibit
      proliferation, apoptosis and metastasis.

PMID- 27894086
TI  - The anti-tumor drug 2-hydroxyoleic acid (Minerval) stimulates signaling and
      retrograde transport.
AB  - 2-hydroxyoleic acid (OHOA, Minerval(r)) is an example of a substance used for
      membrane lipid therapy, where the cellular membranes rather than specific
      proteins constitute the therapeutical target. OHOA is thought to mediate its anti
      tumor effect by affecting the biophysical properties of membranes, which leads to
      altered recruitment and activation of amphitropic proteins, altered cellular
      signaling, and eventual cell death. Little is known about the initial signaling
      events upon treatment with OHOA, and whether the altered membrane properties
      would have any impact on the dynamic intracellular transport system. In the
      present study we demonstrate that treatment with OHOA led to a rapid release of
      intracellular calcium and activation of multiple signaling pathways in HeLa
      cells, including the PI3K-AKT1-MTOR pathway and several MAP kinases, in a process
      independent of the EGFR. By lipidomics we confirmed that OHOA was incorporated
      into several lipid classes. Concomitantly, OHOA potently increased retrograde
      transport of the plant toxin ricin from endosomes to the Golgi and further to the
      endoplasmic reticulum. The OHOA-stimulated ricin transport seemed to require
      several amphitropic proteins, including Src, phospholipase C, protein kinase C,
      and also Ca2+/calmodulin. Interestingly, OHOA induced a slight increase in
      endosomal localization of the retromer component VPS35. Thus, our data show that
      addition of a lipid known to alter membrane properties not only affects
      signaling, but also intracellular transport.

PMID- 27894088
TI  - LSD1 binds to HPV16 E7 and promotes the epithelial-mesenchymal transition in
      cervical cancer by demethylating histones at the Vimentin promoter.
AB  - Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3
      lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found
      that ectopic expression of LSD1 in cervical cancer cells promoted invasion and
      metastasis in vitro and in vivo, reduced the expression of the epithelial marker
      E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By
      contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7
      induced epithelial-mesenchymal transition (EMT). We proposed a novel mechanism,
      whereby LSD1 is recruited to the Vimentin promoter and demethylates H3K4me1 and
      H3K4me2. Notably, HPV16 E7 enhanced the expression of LSD1, formed a complex with
      LSD1, and suppressed LSD1 demethylase activity by hindering the recruitment of
      LSD1 to the Vimentin promoter. Thus, LSD1 is a primary and positive regulator of
      the HPV16 E7-induced EMT and an attractive therapeutic target for alleviating
      HPV16 E7-induced EMT and tumor metastasis.

PMID- 27894090
TI  - Gremlin promotes retinal pigmentation epithelial (RPE) cell proliferation,
      migration and VEGF production via activating VEGFR2-Akt-mTORC2 signaling.
AB  - Retinopathy of prematurity (ROP) is characterized by late-phase pathologic
      retinal vasoproliferation. Gremlin is a novel vascular endothelial growth factors
      (VEGF) receptor 2 (VEGFR2) agonist and promotes angiogenic response. We
      demonstrated that gremlin expression was significantly increased in retinas of
      ROP model mice, which was correlated with VEGF upregulation. In retinal
      pigmentation epithelial (RPE) cells, gremlin activated VEGFR2-Akt-mTORC2
      (mammalian target of rapamycin complex 2) signaling, and promoted cell
      proliferation, migration and VEGF production. VEGFR inhibition (by SU5416) or
      shRNA knockdown almost abolished gremlin-mediated pleiotropic functions in RPE
      cells. Further, pharmacological inhibition of Akt-mTOR, or shRNA knockdown of key
      mTORC2 component (Rictor or Sin1) also attenuated gremlin-exerted activities in
      RPE cells. We conclude that gremlin promotes RPE cell proliferation, migration
      and VEGF production possibly via activating VEGFR2-Akt-mTORC2 signaling. Gremlin
      could be a novel therapeutic target of ROP or other retinal vasoproliferation
      diseases.

PMID- 27894089
TI  - Associations between single-nucleotide polymorphisms of human exonuclease 1 and
      the risk of hepatocellular carcinoma.
AB  - Human exonuclease 1 (hEXO1) is an important nuclease involved in mismatch repair
      system that contributes to maintain genomic stability and modulate DNA
      recombination. This study is aimed to explore the associations between single
      nucleotide polymorphisms (SNPs) of hEXO1 and the hereditary susceptibility of
      hepatocellular carcinoma (HCC). SNPs rs1047840, rs1776148, rs3754093, rs4149867,
      rs4149963, and rs1776181 of hEXO1 were examined from a hospital-based case
      control study including 1,196 cases (HCC patients) and 1,199 controls (non-HCC
      patients) in Guangxi, China. We found the rs3754093 AG genotype decreased the
      risk of HCC (OR=0.714, 95% CI: 0.539~0.946). According to the results of
      stratification analysis, rs3754093 mutant genotype AG/GG decreased the risk of
      HCC with some HCC protective factors such as non-smoking, non-alcohol consumption
      and non-HCC family history, but also decreased the risk of HCC with HBV
      infection. Moreover, it was correlated to non-tumor metastasis and increased the
      survival of HCC patients. The results from gene-environment interaction assay
      indicated all hEXO1 SNPs interacted with smoking, alcohol consumption, HBV
      infection in pathogenesis of HCC. However, gene-gene interaction assay suggested
      the interaction between rs3754093 and other 5 SNPs were associated with reducing
      the HCC risk. These results suggest rs3754093 exhibits a protective activity to
      decrease the incidence risk of HCC in Guangxi, China. In addition, all SNPs in
      this study interacted with environment risk factors in pathogenesis of HCC.

PMID- 27894091
TI  - Preclinical study of cinobufagin as a promising anti-colorectal cancer agent.
AB  - Here, we assessed the anti-colorectal cancer (CRC) cell activity of cinobufagin
      (CBG). We found that CBG exerted potent cytotoxic and anti-proliferative activity
      against CRC lines (HCT-116 and HT-29) and primary human CRC cells. Meanwhile, it
      activated apoptosis, and disrupted cell-cycle progression in the cells. At the
      signaling level, CBG treatment in CRC cells provoked endoplasmic reticulum stress
      (ER stress), the latter was evidenced by caspase-12 activation, CHOP expression,
      as well as PERK and IRE1 phosphorylations. Contrarily, the ER stress inhibitor
      salubrinal, the caspase-12 inhibitor and CHOP shRNA remarkably attenuated CBG
      induced CRC cell death and apoptosis. Further, CBG in-activated mammalian target
      or rapamycin complex 1 (mTORC1), which appeared responsible for proliferation
      inhibition in CRC cells. Introduction of a constitutively-active S6K1 ("ca-S6K1")
      restored proliferation of CBG-treated CRC cells. Finally, CBG intraperitoneal
      injection suppressed HCT-116 xenograft tumor growth in the nude mice. CHOP
      upregulation and mTORC1 in-activation were also noticed in CBG-treated HCT-116
      tumors. The results of this preclinical study suggest that CBG could be tested as
      promising anti-CRC agent.

PMID- 27894093
TI  - New use of an old drug: inhibition of breast cancer stem cells by benztropine
      mesylate.
AB  - Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis,
      recurrence and therapeutic resistance. Targeting CSCs represents a promising
      strategy for cancer treatment. The purpose of this study was to identify
      selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based
      phenotypic screening with cell viability as a primary endpoint, using a
      collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed
      by malignant human breast gland-derived cells (HMLER-shEcad cells, representing
      BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells,
      representing normal stem cells). 19 compounds were identified from screening. The
      chemically related molecules benztropine mesylate and deptropine citrate were
      selected for further validation and both potently inhibited sphere formation and
      self-renewal of BCSCs in vitro. Benztropine mesylate treatment decreased cell
      subpopulations with high ALDH activity and with a CD44+/CD24- phenotype. In vivo,
      benztropine mesylate inhibited tumor-initiating potential in a 4T1 mouse model.
      Functional studies indicated that benztropine mesylate inhibits functions of CSCs
      via the acetylcholine receptors, dopamine transporters/receptors, and/or
      histamine receptors. In summary, our findings identify benztropine mesylate as an
      inhibitor of BCSCs in vitro and in vivo. This study also provides a screening
      platform for identification of additional anti-CSC agents.

PMID- 27894092
TI  - A novel fully human anti-NCL immunoRNase for triple-negative breast cancer
      therapy.
AB  - Breast cancer is the most common cancer in women worldwide. A new promising anti
      cancer therapy involves the use of monoclonal antibodies specific for target
      tumor-associated antigens (TAAs). A TAA of interest for immunotherapy of Triple
      Negative Breast Cancer (TNBC) is nucleolin (NCL), a multifunctional protein,
      selectively expressed on the surface of cancer cells, which regulates the
      biogenesis of specific microRNAs (miRNAs) involved in tumor development and drug
      resistance. We previously isolated a novel human anti-NCL scFv, called 4LB5, that
      is endowed with selective anti-tumor effects. Here we report the construction and
      characterization of a novel immunoRNase constituted by 4LB5 and a human
      pancreatic RNase (HP-RNase) called "4LB5-HP-RNase". This immunoRNase retains both
      the enzymatic activity of human pancreatic RNase and the specific binding of the
      parental scFv to a panel of surface NCL-positive breast cancer cells. Notably,
      4LB5-HP-RNase dramatically and selectively reduced the viability and
      proliferation of NCL-positive tumor cells in vitro and in vivo. Specifically, it
      induced apoptosis and reduced the levels of the tumorigenic miRNAs miR-21, -221
      and -222. Thus, this novel immunoagent could be a valuable tool for the treatment
      of TNBC patients ineligible for currently available targeted treatments.

PMID- 27894094
TI  - MET expression and copy number status in clear-cell renal cell carcinoma:
      prognostic value and potential predictive marker.
AB  - Multiple targeted therapy for advanced clear-cell renal cell carcinoma (RCC) has
      substantially improved patient outcome, but complete remission is uncommon and
      many tumors eventually develop resistance. Mechanistic, preclinical, and early
      clinical data highlight c-Met / hepatocyte growth factor receptor as a promising
      target for RCC therapeutic agents.We have examined MET expression, frequency of
      MET gene copy gains and MET gene mutation in a large, hospital-based series of
      renal cell carcinomas with long-term follow-up information.Out of a total of 572
      clear-cell RCC, only 17% were negative for MET expression whereas 32% showed high
      protein levels. High MET expression and MET copy number gains were associated
      with an aggressive phenotype and an unfavorable patient outcome. Elevated protein
      levels in absence of gene amplification were not attributed to mutations, based
      on results of targeted next-generation sequencing.Our data reveal that clear-cell
      RCC with MET upregulation show an aggressive behavior and MET copy number
      increase is evident in a substantial percentage of patients with high-grade
      carcinomas and metastatic disease. Diagnostic assessment of MET expression and
      amplification may be of predictive value to guide targeted therapy against MET
      signaling in patients with clear-cell RCC.

PMID- 27894095
TI  - MicroRNA-182 drives colonization and macroscopic metastasis via targeting its
      suppressor SNAI1 in breast cancer.
AB  - Metastasis is a multi-step process. Tumor cells occur epithelial-mesenchymal
      transition (EMT) to start metastasis, then, they need to undergo a reverse
      progression of EMT, mesenchymal-epithelial transition (MET), to colonize and form
      macrometastases at distant organs to complete the whole process of metastasis.
      Although microRNAs (miRNAs) functions in EMT process are well established, their
      influence on colonization and macrometastases formation remains unclear. Here, we
      established an EMT model in MCF-10A cells with SNAI1 overexpression, and
      characterized some EMT-related microRNAs. We identified that miR-182, which was
      directly suppressed by SNAI1, could enable an epithelial-like state in breast
      cancer cells in vitro, and enhance colonization and macrometastases in vivo.
      Subsequent studies showed that miR-182 exerted its function through targeting its
      suppressor SNAI1. Moreover, higher expression level of miR-182 was detected in
      metastatic lymph nodes, compared with paired primary tumor tissues. In addition,
      the expression level of miR-182 was negatively correlated with that of SNAI1 in
      these clinical specimens. Taking together, our findings describe the role of miR
      182 in colonization and macrometastases in breast cancer for the first time, and
      provide a promise for diagnosis or therapy of breast cancer metastasis.

PMID- 27894096
TI  - Shed urinary ALCAM is an independent prognostic biomarker of three-year overall
      survival after cystectomy in patients with bladder cancer.
AB  - Proteins involved in tumor cell migration can potentially serve as markers of
      invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes
      adhesion, while shedding of its extracellular domain is associated with
      migration. We hypothesized that shed ALCAM in biofluids could be predictive of
      progressive disease. ALCAM expression in tumor (n = 198) and shedding in
      biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy
      cohorts by immunofluorescence and enzyme-linked immunosorbent assay,
      respectively. The primary outcome measure was accuracy of predicting 3-year
      overall survival (OS) with shed ALCAM compared to standard clinical indicators
      alone, assessed by multivariable Cox regression and concordance-indices.
      Validation was performed by internal bootstrap, a cohort from a second
      institution (n = 64), and treatment of missing data with multiple-imputation.
      While ALCAM mRNA expression was unchanged, histological detection of ALCAM
      decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was
      elevated 17.0-fold (P < 0.0001) above non-cancer controls, correlated positively
      with tumor stage (P = 0.018), was an independent predictor of OS after adjusting
      for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03
      2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5%
      vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting
      for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node
      dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy
      (HR, 1.10; 95% CI, 1.02-1.19; P = 0.011). In conclusion, shed ALCAM may be a
      novel prognostic biomarker in bladder cancer, although prospective validation
      studies are warranted. These findings demonstrate that markers reporting on cell
      motility can act as prognostic indicators.

PMID- 27894097
TI  - A combination of Nottingham prognostic index and IHC4 score predicts pathological
      complete response of neoadjuvant chemotherapy in estrogen receptor positive
      breast cancer.
AB  - Pathologic complete response (pCR) prediction after neoadjuvant chemotherapy
      (NAC) is important for clinical decision-making in breast cancer. This study
      investigated the predictive value of Nottingham prognostic index (NPI),
      Immunohistochemical four (IHC4) score and a new predictive index combined with
      them in estrogen-positive (ER+) breast cancer following NAC. We retrospectively
      gathered clinical data of 739 ER+ breast cancer patients who received NAC from
      two cancer centers. We developed a new predictive biomarker named NPI+IHC4 to
      predict pCR in ER+ breast cancer in a training set (n=443) and validated it in an
      external validation set (n=296). The results showed that a lower IHC4 score, NPI
      and NPI+IHC4 were significantly associated a high pCR rate in the entire cohort.
      In the study set, NPI+IHC4 showed a better sensitivity and specificity for pCR
      prediction (AUC 0.699, 95% CI 0.626-0.772) than IHC4 score (AUC 0.613, 95% CI
      0.533-0.692), NPI (AUC 0.576, 95% CI 0.494-0.659), tumor size (AUC 0.556, 95% CI
      0.481-0.631) and TNM stage (AUC 0.521, 95% CI 0.442-0.601). In the validation
      set, NPI+IHC4 had a better predictive value for pCR (AUC 0.665, 95% CI 0.579
      0.751) than IHC4 score or NPI alone. In addition, ER+ patients with lower IHC4,
      NPI and NPI+IHC4 scores had significantly better DFS in both study and validation
      sets. In summary, NPI+IHC4 can predict pCR following NAC and prognosis in ER+
      breast cancer, which is cost-effect and potentially more useful in guiding
      decision-making regarding NAC in clinical practice. Further validation is needed
      in prospective clinical trials with larger cohorts of patients.

PMID- 27894100
TI  - Investigation of long-term survival outcomes and failure patterns of patients
      with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a
      retrospective analysis.
AB  - Intensity-modulated radiotherapy (IMRT) has replaced the conventional
      radiotherapy (2D-RT) and improved clinical efficacy in Nasopharyngeal Carcinoma
      (NPC) patients. In the present study, we retrospectively analyzed the clinical
      characteristics of patients with NPC treated with IMRT to assess the long-term
      survival outcomes and failure patterns. Of the 527 patients, One hundred and
      twenty-one patients experienced treatment failure, 86 patients developed distant
      metastases, and 12 patients developed a second primary tumor. The local and
      regional recurrence rates were 31.4% and 14.0%, respectively. The 5-year overall
      survival (OS), progression-free survival (PFS), local recurrence-free survival
      (LRFS), regional relapse-free survival (RRFS), and distant metastatic relapse
      free survival (DMFS) rates were 80.9%, 75.6%, 91.7%, 96.2%, and 83.0%,
      respectively. The 5-year LRFS rates of Stage T1-4 patients were 100.0%, 93.1%,
      92.0%, and 85.8%, respectively. The 5-year DMFS rates of Stage N0-3 patients were
      95.0%, 86.1%, 79.5%, and 67.2%, respectively. Multivariate analysis showed age
      and T-stage were independent predictors of OS, T-stage was an independent
      predictor of LRFS, and age and N-stage were independent predictors of PFS and
      DMFS.In summary, the improved treatment results with IMRT are primarily due to
      the achievement of a higher local tumor control rate and OS in NPC patients.
      However, distant metastasis was the most commonly observed failure pattern after
      treatment. These results provide deep insights about the value of IMRT in the
      treatment and prognosis of NPC patients.

PMID- 27894099
TI  - Peroxiredoxin 2 is essential for maintaining cancer stem cell-like phenotype
      through activation of Hedgehog signaling pathway in colon cancer.
AB  - Cancer stem cells (CSCs) are a key target for reducing tumor growth, metastasis,
      and recurrence. Redox status is a critical factor in the maintenance of CSCs, and
      the antioxidant enzyme Peroxiredoxin 2 (Prdx2) plays an important role in the
      development of colon cancer. Therefore, we investigated the contribution of Prdx2
      to the maintenance of stemness of colon CSCs. Here, we used short-hairpin RNAs
      and a Prdx2-overexpression vector to determine the effects of Prdx2. We
      demonstrated that knockdown of Prdx2 reduced the self-renewal and sphere
      formation and resulted in increased 5-FU-induced apoptosis in human colon CSCs.
      Prdx2 overexpression induced reversion of the self-renewal and sphere formation.
      Furthermore, the effects of Prdx2 resulted in an altered expression of stemness
      associated with the Hh/Gli1 signaling pathway. Finally, knockdown of Prdx2 in
      CD133+ cells reduced the volume of xenograft tumors in BALB/c-nu mice. Taken
      together, colon CSCs overexpress Prdx2, which promotes their stem cell properties
      via the Hh/Gli1 signaling pathway. The results suggest that Prdx2 may be an
      effective therapeutic target for the elimination of CSCs in colorectal cancer.

PMID- 27894101
TI  - Impact of hematological inflammatory markers on clinical outcome in patients with
      salivary duct carcinoma: a multi-institutional study in Japan.
AB  - The prognostic role of modified Glasgow Prognostic Score (mGPS), neutrophil-to
      lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with
      salivary duct carcinoma (SDC) remains unclear. We conducted a multi-institutional
      retrospective cohort study of 140 SDC patients. The survival impact of these
      hematological markers was evaluated using multivariate proportional hazard
      models.High mGPS (>=1) was significantly associated with worse survival (3-year
      overall survival (OS): 16.7% vs 66.1%, p-value=0.003; 3-year progression-free
      survival (PFS): 0.0% vs 27.9%, p-value<0.001). Additionally, high C-reactive
      protein (CRP) (>=0.39 mg/dl) was significantly associated with worse survival (3
      year OS: 32.1% vs 68.2%, p-value=0.001; 3-year PFS: 7.1% vs 31.1%, p
      value<0.001). These associations were consistent with multivariate analysis
      adjusted for established prognostic factors. Although we also found significant
      association of high NLR (>=2.5) with OS (HR 1.80; 95% confidence interval, 1.05
      3.08) in multivariate analysis, this association were inconsistent with the
      results of PFS. In addition, we found no significant associations of PLR with
      survival. In conclusion, we found that mGPS, CRP and NLR were identified as
      prognostic factors associated with survival in SDC patients.

PMID- 27894103
TI  - An efficient iterative CBCT reconstruction approach using gradient projection
      sparse reconstruction algorithm.
AB  - The purpose of this study is to develop a fast and convergence proofed CBCT
      reconstruction framework based on the compressed sensing theory which not only
      lowers the imaging dose but also is computationally practicable in the busy
      clinic. We simplified the original mathematical formulation of gradient
      projection for sparse reconstruction (GPSR) to minimize the number of forward and
      backward projections for line search processes at each iteration. GPSR based
      algorithms generally showed improved image quality over the FDK algorithm
      especially when only a small number of projection data were available. When there
      were only 40 projections from 360 degree fan beam geometry, the quality of GPSR
      based algorithms surpassed FDK algorithm within 10 iterations in terms of the
      mean squared relative error. Our proposed GPSR algorithm converged as fast as the
      conventional GPSR with a reasonably low computational complexity. The outcomes
      demonstrate that the proposed GPSR algorithm is attractive for use in real time
      applications such as on-line IGRT.

PMID- 27894102
TI  - Comparative proteomics of a model MCF10A-KRasG12V cell line reveals a distinct
      molecular signature of the KRasG12V cell surface.
AB  - Oncogenic Ras mutants play a major role in the etiology of most aggressive and
      deadly carcinomas in humans. In spite of continuous efforts, effective
      pharmacological treatments targeting oncogenic Ras isoforms have not been
      developed. Cell-surface proteins represent top therapeutic targets primarily due
      to their accessibility and susceptibility to different modes of cancer therapy.
      To expand the treatment options of cancers driven by oncogenic Ras, new targets
      need to be identified and characterized at the surface of cancer cells expressing
      oncogenic Ras mutants. Here, we describe a mass spectrometry-based method for
      molecular profiling of the cell surface using KRasG12V transfected MCF10A (MCF10A
      KRasG12V) as a model cell line of constitutively activated KRas and native MCF10A
      cells transduced with an empty vector (EV) as control. An extensive molecular map
      of the KRas surface was achieved by applying, in parallel, targeted hydrazide
      based cell-surface capturing technology and global shotgun membrane proteomics to
      identify the proteins on the KRasG12V surface. This method allowed for integrated
      proteomic analysis that identified more than 500 cell-surface proteins found
      unique or upregulated on the surface of MCF10A-KRasG12V cells. Multistep
      bioinformatic processing was employed to elucidate and prioritize targets for
      cross-validation. Scanning electron microscopy and phenotypic cancer cell assays
      revealed changes at the cell surface consistent with malignant epithelial-to
      mesenchymal transformation secondary to KRasG12V activation. Taken together, this
      dataset significantly expands the map of the KRasG12V surface and uncovers
      potential targets involved primarily in cell motility, cellular protrusion
      formation, and metastasis.

PMID- 27894104
TI  - Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein
      cargo and cancer type-specific biomarkers.
AB  - Packed with biological information, extracellular vesicles (EVs) offer exciting
      promise for biomarker discovery and applications in therapeutics and non-invasive
      diagnostics. Currently, our understanding of EV contents is confined by the
      limited cells from which vesicles have been characterized utilizing the same
      enrichment method. Using sixty cell lines from the National Cancer Institute (NCI
      60), here we provide the largest proteomic profile of EVs in a single study,
      identifying 6,071 proteins with 213 common to all isolates. Proteins included
      established EV markers, and vesicular trafficking proteins such as Rab GTPases
      and tetraspanins. Differentially-expressed proteins offer potential for cancer
      diagnosis and prognosis. Network analysis of vesicle quantity and proteomes
      identified EV components associated with vesicle secretion, including CD81, CD63,
      syntenin-1, VAMP3, Rab GTPases, and integrins. Integration of vesicle proteomes
      with whole-cell molecular profiles revealed similarities, suggesting EVs provide
      a reliable reflection of their progenitor cell content, and are therefore
      excellent indicators of disease.

PMID- 27894098
TI  - Impact of Mediterranean diet on metabolic syndrome, cancer and longevity.
AB  - Obesity symbolizes a major public health problem. Overweight and obesity are
      associated to the occurrence of the metabolic syndrome and to adipose tissue
      dysfunction. The adipose tissue is metabolically active and an endocrine organ,
      whose dysregulation causes a low-grade inflammatory state and ectopic fat
      depositions. The Mediterranean Diet represents a possible therapy for metabolic
      syndrome, preventing adiposopathy or "sick fat" formation.The Mediterranean Diet
      exerts protective effects in elderly subjects with and without baseline of
      chronic diseases. Recent studies have demonstrated a relationship between cancer
      and obesity. In the US, diet represents amount 30-35% of death causes related to
      cancer. Currently, the cancer is the second cause of death after cardiovascular
      diseases worldwide. Furthermore, populations living in the Mediterranean area
      have a decreased incidence of cancer compared with populations living in Northern
      Europe or the US, likely due to healthier dietary habits. The bioactive food
      components have a potential preventive action on cancer. The aims of this review
      are to evaluate the impact of Mediterranean Diet on onset, progression and
      regression of metabolic syndrome, cancer and on longevity.

PMID- 27894105
TI  - Histone deacetylase inhibitors provoke a tumor supportive phenotype in pancreatic
      cancer associated fibroblasts.
AB  - Although histone deacetylase inhibitors (HDACi) are a promising class of anti
      cancer drugs, thus far, they have been unsuccessful in early phase clinical
      trials for pancreatic ductal adenocarcinoma (PDAC). One potential reason for
      their poor efficacy is the tumor stroma, where cancer-associated fibroblasts
      (CAFs) are a prominent cell type and a source of resistance to cancer therapies.
      Here, we demonstrate that stromal fibroblasts contribute to the poor efficacy of
      HDACi's in PDAC. HDACi-treated fibroblasts show increased biological
      aggressiveness and are characterized by increased secretion of pro-inflammatory
      tumor-supportive cytokines and chemokines. We find that HDAC2 binds to the
      enhancer and promoter regions of pro-inflammatory genes specifically in CAFs and
      in silico analysis identified AP-1 to be the most frequently associated
      transcription factor bound in these regions. Pharmacologic inhibition of pathways
      upstream of AP-1 suppresses the HDACi-induced inflammatory gene expression and
      tumor-supportive responses in fibroblasts. Our findings demonstrate that the
      combination of HDACi's with chemical inhibitors of the AP-1 signaling pathway
      attenuate the inflammatory phenotype of fibroblasts and may improve the efficacy
      of HDACi in PDAC and, potentially, in other solid tumors rich in stroma.

PMID- 27894107
TI  - Effect of Gonadal Hormones on Neurotransmitters Implicated in the Pathophysiology
      of Obsessive-Compulsive Disorder: A Critical Review.
AB  - Obsessive-compulsive disorder (OCD) is a relatively common neuropsychiatric
      disorder affecting between 1.6 and 3.2% of the population. A number of studies
      have previously reported increased incidence of OCD, or exacerbation of
      preexisting symptoms in females during reproductive events. Since these periods
      are known to involve fluctuating levels of gonadal hormones, these steroids have
      been suggested to be involved in modulating the course of the disorder. However,
      to date, only a few studies have measured hormone levels and obsessive-compulsive
      (OC) symptoms concurrently; thus, direct evidence for this relationship is
      limited. In turn, investigations into neurotransmission in OC individuals have
      been more extensive, and have implicated the serotonergic, dopaminergic, and
      glutamatergic neurotransmitter systems in OCD pathology. There is evidence
      suggesting that reproductive hormones estrogens and progesterone can modulate
      neurotransmission in the aforementioned signaling pathways by regulating the
      expression of receptors and channels, as well as the synthesis and release of the
      neurotransmitter itself. Overall, estrogen and progesterone appear to enhance
      serotonin signaling, which has been associated with improved OC symptoms. The
      effect of the gonadal hormones in dopaminergic and glutamatergic signaling is
      much more variable, highlighting the need for further research in this field. The
      existing evidence shows that gonadal hormones can have profound impacts on
      neurotransmission in the brain, leading to the conclusion that the hormonal
      fluctuations during reproductive events are a plausible factor contributing to
      the change in OCD course during these times.

PMID- 27894106
TI  - Prader-Willi Syndrome due to an Unbalanced de novo Translocation
      t(15;19)(q12;p13.3).
AB  - Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder
      characterized by endocrine, neurologic, and behavioral abnormalities. We report
      the first case of an unbalanced de novo reciprocal translocation of chromosomes
      15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the
      PWS critical chromosome region. Our patient had several typical features of PWS
      including infantile hypotonia, a poor suck and feeding difficulties, tantrums,
      skin picking, compulsions, small hands and feet, and food seeking, but not
      hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen
      in PWS at the time of examination at 6 years of age. He had seizures noted from 1
      to 3 years of age and marked cognitive delay. High-resolution SNP microarray
      analysis identified an atypical PWS type I deletion in chromosome 15 involving
      the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was
      proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and
      GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was
      detected; therefore, the patient was not at an increased risk of tumors from the
      Peutz-Jeghers syndrome associated with a deletion of the STK11 gene.

PMID- 27894108
TI  - Nutrition Status, Nutrition Support Therapy, and Food Intake are Related to
      Prolonged Hospital Stays in China: Results from the NutritionDay 2015 Survey.
AB  - BACKGROUND AND AIMS: Malnutrition is a common and critical problem that greatly
      influences the clinical outcomes of hospitalized patients. Nutrition support
      therapy and food intake, in addition to disease-related factors, are also
      important to maintain the nutrition status of patients. In light of this, we
      aimed to examine the risk factors associated with malnutrition in 3 hospitals in
      China. METHODS: This project was part of the NutritionDay audit, an international
      daylong cross-sectional audit investigating the nutritional intervention profiles
      of hospitalized patients. Seven standardized questionnaires were used, and
      malnutrition was defined as a body mass index <18.5 kg/m2 or unintentional weight
      loss >5% in last 3 months. RESULTS: A total of 842 hospitalized patients from 9
      units in 3 Chinese hospitals participated in the project on November 19, 2015.
      Among them, 825 were included in the analyses. Malnutrition was identified in
      29.3% of the patients and oral nutrition was the primary nutrition support
      therapy administered (n = 623, 75.6%). Age, nutrition support, and food intake
      during the past week were independent risk factors for malnutrition. Furthermore,
      nutrition status, nutrition support therapy, and food intake during the past week
      were associated with prolonged length of stay. CONCLUSIONS: The prevalence of
      malnutrition in Chinese hospitals was similar to that in European hospitals.
      Nutrition status was associated with age, nutrition support, and food intake,
      which was closely related to patients' clinical outcome, such as prolonged
      hospital stays as confirmed in this study. More studies are needed to determine
      why nutrition intake is often inadequate and to determine efficient methods for
      correcting the nutrition status of patients.

PMID- 27894109
TI  - Ozone Therapy and Its Use in Medicine: Further Comments.

PMID- 27894111
TI  - Distribution of the Grey Slender Loris (Loris lyddekerianus Cabrera, 1908) in
      Tamil Nadu, Southern India.
AB  - The grey slender loris Loris lydekkerianus, one of only two nocturnal primates of
      India, is found in the southern part of the country. Our understanding of its
      geographical distribution is largely based on historical records and short
      surveys, and little is known of its occurrence in southern India today. We sought
      to establish the relative abundance of this species in 26 districts in the state
      of Tamil Nadu and the union territory of Pondicherry in southern India. We
      sighted lorises in 19 districts, and their relative abundance ranged from 0.01 to
      2.21/km. The south-central districts of Tamil Nadu showed the highest densities
      of lorises, while the western districts showed the lowest. Based on these
      results, we recommend increased protection measures for the forest patches of the
      Eastern Ghats mountains in order to ensure the long-term survival of the grey
      slender loris.

PMID- 27894110
TI  - Significant Role(s) of CXCL12 and the SDF-1 3'A Genetic Variant in the
      Pathogenesis of Multiple Sclerosis.
AB  - Both cellular and molecular components of the immune system are among the
      substantial factors involved in the pathogenesis of multiple sclerosis (MS).
      Accumulating evidence confirms that chemokines, as the main members of the immune
      system, play key roles in the regulation of immune responses. Immune system
      genetic parameters are believed to influence the onset of immune system-related
      diseases. Regarding the significant role of the CXCR4/CXCL12 axis in cell
      differentiation and survival and homing of hematopoietic progenitors to the bone
      marrow and regulation of neuronal progenitor cell migration in the central
      nervous system (CNS), genetic factors can cause an increased expression of CXCL12
      and induce a vigorous immune response against CNS antigens in MS patients.
      Previous studies have indicated that the expression of CXCL12 could be affected
      by its polymorphisms at position +801 at the region of the CXCL12 3'A genetic
      variation. Finally, CXCL12 seems to be involved in the cellular part of the
      events that take place in the CNS, and therefore it could be considered as a
      target in MS therapies. Thus, this review was aimed to describe the recent
      progress in understanding the role of CXCL12 in MS, with an emphasis on CXCL12
      serum concentrations and its gene polymorphism at position +801.

PMID- 27894112
TI  - Association of MBL2 Gene Polymorphism with Dental Caries in Saudi Children.
AB  - The high prevalence of dental caries in children worldwide is a major oral health
      problem which requires early intervention. Dental caries is mainly caused by the
      action of acids produced by bacteria in addition to many other factors. Recent
      genetic studies have reported that a number of genes are associated with the
      susceptibility to dental caries. The majority of these genes are associated with
      inflammation, increased susceptibility to infection, and dentine matrix
      formation. Using the TaqMan assay and direct DNA sequencing, the prevalence of 6
      single-nucleotide polymorphisms (SNPs) in MMP9, MBL2, MMP2, and TIMP2 genes was
      determined in 102 children with caries and in 100 age-matched caries-free
      controls. Out of the 6 SNPs tested in the 4 selected genes, only rs11003125 in
      the MBL2 gene was shown to be associated with a high prevalence of caries in our
      cohort. In addition, haplotype analysis of the 6 SNPs tested revealed that
      certain haplotypes, namely GT of rs11003125G and rs7501477T and GT of rs7096206G
      and rs7501477T, were found to be associated with a high prevalence of dental
      caries in our cohort, while haplotype AG of rs17576A and rs7501477G was found to
      have a protective effect against dental caries. In conclusion, the data indicate
      that rs11003125 in the MBL2 gene was shown to be associated with a high
      prevalence of caries in our cohort, and 2 haplotypes are also involved in the
      increased susceptibility to dental caries.

PMID- 27894113
TI  - The Evolving Role of Biomarkers in Personalized Lung Cancer Therapy.

PMID- 27894115
TI  - Complement Activation-Related Pseudo-Allergy: A Fresh Look at Hypersensitivity
      Reactions to Intravenous Iron.

PMID- 27894114
TI  - Hydroxysafflor Yellow A Promotes Angiogenesis via the Angiopoietin 1/ Tie-2
      Signaling Pathway.
AB  - BACKGROUND: The flowers of Carthamus tinctorius L. are widely used in traditional
      Chinese medicine to treat cerebrovascular and cardiovascular diseases.
      Hydroxysafflor yellow A (HSYA), the main constituent of C. tinctorius L. flowers,
      is known for its multiple biological activities. The present study investigated
      the effects of HSYA on angiogenesis in vitro and in a mouse hindlimb ischemia
      model. METHODS: Using human umbilical vein endothelial cells (HUVEC) in vitro and
      a mouse hindlimb ischemia model in vivo, the angiogenic role of HSYA was
      evaluated. RESULTS: HSYA significantly increased the capillary-like tube
      formation and migration of HUVEC. HSYA not only induced a rise in the expression
      of angiopoietin 1 and Tie-2 but it also increased phosphorylation of Tie-2, Akt,
      and extracellular signal-regulated kinase 1/2. Furthermore, an anti-Tie-2
      neutralizing antibody significantly inhibited HSYA-induced HUVEC tube formation
      and migration. In vivo, the recovery of perfusion of ischemic hindlimb tissue
      after femoral artery interruption was significantly increased in HSYA-treated
      mice compared to vehicle controls. Consistent with these results, the arteriole
      and capillary densities in ischemic gastrocnemius muscles were significantly
      increased in HSYA-treated mice. CONCLUSIONS: These results indicate the potential
      utility of HSYA for the treatment of ischemic diseases.

PMID- 27894116
TI  - Intrarenal Vascular Resistance is Associated With a Prothrombotic State in
      Hypertensive Patients.
AB  - BACKGROUND/AIMS: Hypertensive nephroangiosclerosis is associated with progressive
      increase of intrarenal vascular resistance. In addition to blood pressure, other
      factors can contribute to hypertensive renal damage including a prothrombotic
      state. We investigated the relationship between hemostatic markers and intrarenal
      vascular resistance in hypertension. METHODS: In 115 untreated, nondiabetic,
      hypertensive subjects free of cardiovascular complications and advanced renal
      function impairment, we measured 24-hour creatinine clearance (GFR) and urinary
      albumin excretion (UAE), fasting plasma glucose, HOMA-index, and plasma levels of
      fibrinogen, D-dimer, prothrombin fragment 1+2, plasminogen activator inhibitor-1,
      homocysteine, and lipoprotein(a). In all patients, measurement of intrarenal
      resistance was obtained by renal Doppler ultrasound with calculation of the renal
      resistance index (RI). RESULTS: Patients in the highest tertile of RI were older
      and had greater body mass index, pulse pressure, fibrinogen, and D-dimer levels
      and lower GFR than patients in the lowest RI tertile. RI was directly correlated
      with age, pulse pressure, HOMA-index, UAE, D-dimer, and inversely with GFR. On
      multivariate analysis, RRI was independently associated with age, GFR, and plasma
      D-dimer. CONCLUSIONS: A prothrombotic state is associated with increased
      intrarenal vascular resistance in nondiabetic hypertensive patients and might
      contribute to the early stages of hypertensive renal disease.

PMID- 27894117
TI  - t(1;9)(p34;q34)/SFPQ-ABL1 Fusion in a Patient with Ph-Like Common B-Cell Acute
      Lymphoblastic Leukemia.

PMID- 27894118
TI  - Nutritional Status and Changes in Body Weight in Patients with Multiple System
      Atrophy.
AB  - INTRODUCTION: The importance of nutritional management in neurodegenerative
      diseases is increasingly recognized in the clinical setting. However, few reports
      have examined the nutritional intake in patients with multiple system atrophy
      (MSA). Here, we investigated changes in daily caloric intake, body mass index
      (BMI) and nutritional status during the disease course of MSA. METHODS: We
      performed a single-hospital study of 82 consecutive patients with probable MSA
      according to the consensus criteria. We determined daily caloric intake, the
      level of activities of daily living (ADL; independent, wheelchair-bound or
      bedridden) and BMI at the time of admission. Nutritional status was also
      evaluated using biochemical nutritional markers including serum albumin, total
      cholesterol and lymphocyte count. RESULTS: Although daily caloric intake
      decreased with ADL level deterioration (p < 0.01), no significant differences
      were observed in BMI among ADL levels. Serum albumin also decreased with ADL
      deterioration (p < 0.01); however, no significant differences were observed for
      serum total cholesterol or lymphocyte count with respect to ADL level.
      CONCLUSION: We demonstrated that patients with advanced stage MSA may develop
      malnutrition in the absence of a decrease in BMI. Moreover, serum albumin level
      may be useful for evaluating nutritional changes in MSA patients.

PMID- 27894119
TI  - Trajectories and Predictors of Allograft Dysfunction after Renal Transplantation
      in Children.
AB  - BACKGROUND: The survival rates of renal transplant children are indeed on the
      rise, but it is still important to ensure that there is optimal renal function in
      these children in all their future growing years. The number of functioning
      nephrons and the graft ability to adapt to an increasing demand during body
      growth seem to be the most important factors for long-term allograft function.
      This study examined the long-term change in the glomerular filtration rate in a
      pediatric kidney transplant cohort and the importance of the recipient and donor
      ages in predicting transplant outcome. METHODS: Data on 67 renal transplant
      children who underwent 278 inulin-clearance measurements between 2000 and 2010
      were examined. A longitudinal latent class model was used to identify renal
      function trajectories and classify the children. RESULTS: This model identified 3
      trajectories of renal allograft function after pediatric kidney transplantation:
      'low and decreasing', 'moderate and stable', and 'high and sharply decreasing'.
      The probability of belonging to the low and decreasing trajectory - that is, the
      poorer outcome - was lower in recipients of grafts from living versus deceased
      donor (adjusted OR (aOR) 0.02; p = 0.03). This probability increased with
      recipient age (aOR 1.20 per year of recipient ageing; p = 0.07) and donor
      recipient age-difference (aOR 1.13 per additional year; p = 0.07). CONCLUSION:
      This study suggests that donation from living donors and from younger donors are
      favorable factors for long-term allograft function.

PMID- 27894120
TI  - End-of-Life Care and Survival without Major Brain Damage in Newborns at the Limit
      of Viability.
AB  - BACKGROUND: The probabilities of survival and survival without major brain damage
      (MBD) are low in newborns at the limit of viability. Survival without MBD
      constitutes a major concern for parents and professionals. OBJECTIVES: To know
      the probabilities of survival without MBD in newborns <=26 weeks' gestational age
      (GA) relative to the total number of survivors, whether these probabilities vary
      with GA, and how end-of-life (EoL) decisions influence these results. METHODS: We
      included all live-inborn patients of 22-26 weeks' GA, without major congenital
      anomalies, born in collaborating centers of the Spanish SEN1500 Network (2004
      2010). MBD was defined as the presence of severe intraventricular hemorrhage
      and/or periventricular leukomalacia. RESULTS: A total of 3,371 patients were born
      alive, 3,236 of whom were admitted to the neonatal intensive care unit (NICU).
      Survival without MBD was 44.4% among patients admitted to the NICU, increasing
      from 12.5% at 22 weeks to 57.9% at 26 weeks' GA. The proportion of survivors
      without MBD relative to the total number of survivors was 81.1%, and it was
      independent of GA. EoL decisions preceded one-third of all deaths and were more
      frequent among the most immature patients. CONCLUSIONS: The proportion of
      survivors without MBD, when referred to the total number of survivors, is
      relatively high and is independent of GA. EoL decisions after the occurrence of
      MBD seem to play an important role in this respect. These results support the
      attitude of "giving an opportunity" even to the most immature patients, if this
      is in accordance with the parents' wishes.

PMID- 27894121
TI  - Acute Disseminated Encephalomyelitis Following Zika Virus Infection.

PMID- 27894122
TI  - B Cell Lymphoma-2-Modified Bone Marrow-Derived Mesenchymal Stem Cells
      Transplantation for the Treatment of Diabetes Mellitus-Induced Erectile
      Dysfunction in a Rat Model.
AB  - OBJECTIVE: The study aimed to explore the effects of B cell lymphoma-2 (Bcl-2)
      modified bone marrow-derived mesenchymal stem cells (BMSCs) transplantation for
      the treatment of diabetes mellitus-induced erectile dysfunction (DMED) in a rat
      model. METHODS: The DMED rat model was successfully established. Thirty-six DMED
      rats were assigned into the Bcl-2-BMSCs, null-BMSCs, BMSCs and phosphate buffered
      saline (PBS) groups. Meanwhile, 9 normal rats injected with PBS were taken as the
      normal control group. RESULTS: In the Bcl-2-BMSCs group, the average times of
      erection, rate of erection, peak intra-cavernous pressure (ICP) and peak ICP/mean
      arterial pressure were higher than those in the null-BMSCs, BMSCs and PBS groups,
      but were lower than those in the normal control group. In the Bcl-2-BMSCs group,
      capillary vessels and Bcl-2 mRNA and protein expressions were similar to those in
      the normal control group, while they were higher than those in other groups.
      CONCLUSION: These findings indicate that Bcl-2-modified BMSC transplantation
      could improve erectile function in DMED rats.

PMID- 27894123
TI  - Safeguarding pollinators and their values to human well-being.
AB  - Wild and managed pollinators provide a wide range of benefits to society in terms
      of contributions to food security, farmer and beekeeper livelihoods, social and
      cultural values, as well as the maintenance of wider biodiversity and ecosystem
      stability. Pollinators face numerous threats, including changes in land-use and
      management intensity, climate change, pesticides and genetically modified crops,
      pollinator management and pathogens, and invasive alien species. There are well
      documented declines in some wild and managed pollinators in several regions of
      the world. However, many effective policy and management responses can be
      implemented to safeguard pollinators and sustain pollination services.

PMID- 27894124
TI  - Extensive degeneracy, Coulomb phase and magnetic monopoles in artificial square
      ice.
AB  - Artificial spin-ice systems are lithographically patterned arrangements of
      interacting magnetic nanostructures that were introduced as way of investigating
      the effects of geometric frustration in a controlled manner. This approach has
      enabled unconventional states of matter to be visualized directly in real space,
      and has triggered research at the frontier between nanomagnetism, statistical
      thermodynamics and condensed matter physics. Despite efforts to create an
      artificial realization of the square-ice model-a two-dimensional geometrically
      frustrated spin-ice system defined on a square lattice-no simple geometry based
      on arrays of nanomagnets has successfully captured the macroscopically degenerate
      ground-state manifold of the model. Instead, square lattices of nanomagnets are
      characterized by a magnetically ordered ground state that consists of local loop
      configurations with alternating chirality. Here we show that all of the
      characteristics of the square-ice model are observed in an artificial square-ice
      system that consists of two sublattices of nanomagnets that are vertically
      separated by a small distance. The spin configurations we image after
      demagnetizing our arrays reveal unambiguous signatures of a Coulomb phase and
      algebraic spin-spin correlations, which are characterized by the presence of
      'pinch' points in the associated magnetic structure factor. Local excitations-the
      classical analogues of magnetic monopoles-are free to evolve in an extensively
      degenerate, divergence-free vacuum. We thus provide a protocol that could be used
      to investigate collective magnetic phenomena, including Coulomb phases and the
      physics of ice-like materials.

PMID- 27894126
TI  - Brain-Type Natriuretic Peptide and Amino-Terminal Pro-Brain-Type Natriuretic
      Peptide Discharge Thresholds for Acute Decompensated Heart Failure: A Systematic
      Review.
AB  - Background: Acute decompensated heart failure (ADHF) requiring hospitalization is
      associated with high postdischarge mortality and readmission rates. Purpose: To
      examine the association between achieving predischarge natriuretic peptide (NP)
      thresholds and mortality and readmission rates in adults hospitalized for ADHF.
      Data Sources: Multiple databases from 1947 to October 2016 (English-language
      studies only). Study Selection: Trials and observational studies that compared
      mortality and readmission outcomes between patients with ADHF achieving a
      specific predischarge NP goal and those not achieving the goal. Data Extraction:
      Two investigators independently extracted study characteristics and assessed
      study risk of bias. One author graded the overall strength of evidence, with
      review by a second author. Data Synthesis: One randomized trial, 3 quasi
      experimental studies, and 40 observational studies were identified. The most
      commonly used thresholds were a brain-type NP (BNP) level of 250 pg/mL or less or
      an amino-terminal pro-brain-type NP (NT-proBNP) decrease of at least 30%.
      Achievement of absolute BNP thresholds reduced postdischarge all-cause mortality
      (7 of 8 studies) and the composite outcome of mortality and readmission (12 of 14
      studies). Achievement of percentage-change BNP thresholds reduced the composite
      outcome (5 of 6 studies), and achievement of percentage-change NT-proBNP
      thresholds reduced all-cause and cardiovascular mortality (2 of 4 studies) and
      the composite outcome (9 of 9 studies). All findings were low-strength. The
      randomized trial, assessed as having high risk of bias, suggested that a
      predischarge decrease in NT-proBNP level was associated with lower risk for the
      composite outcome. Two quasi-experimental studies and 5 observational studies had
      low risk of bias. Low-risk-of-bias studies had outcome estimates similar in
      magnitude and direction to estimates from high-risk-of-bias studies. Limitation:
      Most studies failed to adjust for critical confounders and had inadequate
      definition or assessment of exposures and outcomes. Conclusion: Low-strength
      evidence suggests an association between achieving NP predischarge thresholds and
      reduced ADHF mortality and readmission. Primary Funding Source: None.

PMID- 27894127
TI  - Enhancing the Role of Internists in the Transition From Pediatric to Adult Health
      Care.

PMID- 27894125
TI  - Intronic polyadenylation of PDGFRalpha in resident stem cells attenuates muscle
      fibrosis.
AB  - Platelet-derived growth factor receptor alpha (PDGFRalpha) exhibits divergent
      effects in skeletal muscle. At physiological levels, signalling through this
      receptor promotes muscle development in growing embryos and angiogenesis in
      regenerating adult muscle. However, both increased PDGF ligand abundance and
      enhanced PDGFRalpha pathway activity cause pathological fibrosis. This excessive
      collagen deposition, which is seen in aged and diseased muscle, interferes with
      muscle function and limits the effectiveness of gene- and cell-based therapies
      for muscle disorders. Although compelling evidence exists for the role of
      PDGFRalpha in fibrosis, little is known about the cells through which this
      pathway acts. Here we show in mice that PDGFRalpha signalling regulates a
      population of muscle-resident fibro/adipogenic progenitors (FAPs) that play a
      supportive role in muscle regeneration but may also cause fibrosis when
      aberrantly regulated. We found that FAPs produce multiple transcriptional
      variants of Pdgfra with different polyadenylation sites, including an intronic
      variant that codes for a protein isoform containing a truncated kinase domain.
      This variant, upregulated during regeneration, acts as a decoy to inhibit PDGF
      signalling and to prevent FAP over-activation. Moreover, increasing the
      expression of this isoform limits fibrosis in vivo in mice, suggesting both
      biological relevance and therapeutic potential of modulating polyadenylation
      patterns in stem-cell populations.

PMID- 27894128
TI  - Inpatient Management of Heart Failure: Are We Shooting at the Right Target?

PMID- 27894129
TI  - Isolated Fetal Ascites, Neonatal Outcome in 51 Cases Observed in a Tertiary
      Referral Center.
AB  - Introduction Prenatal detection of isolated ascites is a rare finding on
      ultrasound, usually suggestive of an underlying pathology that may negatively
      impact on the pregnancy and neonatal outcome. The purpose of the present study
      was to evaluate the outcome of primary isolated ascites in relation to
      gestational age (GA) at diagnosis. Materials and Methods Data were prospectively
      collected for fetuses with ascites that have been followed in our center of
      prenatal diagnosis and therapy from 2004 to 2014. Patients have been divided in
      group I when ascites was detected before the 24th week of GA and group II if it
      was noticed later. Prenatal workup included detailed ultrasound, maternal blood
      group and presence of antibodies, maternal infection screening, fetal
      karyotyping, and if needed fetal paracentesis. Postnatal data included GA at
      birth, mode of delivery, weight at birth, neonatal and surgical outcome. Results
      During the study period, 51 fetuses were included. Among them, 28 in group I and
      23 in group II. An associated anomaly was prenatally identified in 84% of the
      fetuses. Prenatal demise occurred only in patients belonging to group I for an
      overall incidence of 10%. An associated disease was confirmed after birth in 61%
      of cases in group I and in 74% in group II (p = ns). There was a higher incidence
      of gastrointestinal pathology in group II than in group I (47 vs. 10%, p =
      0.004); with a significant prevalence of meconium peritonitis (32 vs. 4%, p =
      0.016). Nine patients (17.6%) died after birth, all in group I, because of major
      systemic malformations. Overall, the postnatal outcome was good in 63% (n = 32)
      of the cases, and more than half of them belonged to group II (p = 0.003).
      Conclusion A wide range of etiologies have been found to be associated with
      isolated fetal ascites. A systematic diagnostic workup and multidisciplinary
      prenatal counseling can improve the accuracy of prenatal identification of
      associated pathologies. The early detection of fetal ascites, before the 24th
      week of GA, is associated with a significant risk of perinatal death; otherwise,
      a late diagnosis of fetal ascites is associated with an increased risk of
      gastrointestinal diseases, especially with meconium peritonitis.

PMID- 27894130
TI  - Erratum to: Maternal Mortality in Texas.

PMID- 27894131
TI  - Antioxidant Enzyme Activity and Cognition in Obese Individuals with or without
      Metabolic Risk Factors.

PMID- 27894132
TI  - Video Comment on Pioche et al.

PMID- 27894133
TI  - Video Comment on Mori et al.

PMID- 27894134
TI  - Peroral endoscopic myotomy: ready for prime time in all achalasia patients?

PMID- 27894135
TI  - Achieving the potential of colonoscopy screening.

PMID- 27894136
TI  - Trends in quality of screening colonoscopy in Austria.

PMID- 27894139
TI  - French comment on article: Randomized comparative evaluation of endoscopic
      submucosal dissection self-learning software in France and Japan.

PMID- 27894140
TI  - French comment on article: Peroral endoscopic myotomy: a meta-analysis.

PMID- 27894141
TI  - French comment on article: Comparison of different biopsy forceps models for
      tissue sampling in eosinophilic esophagitis.

PMID- 27894142
TI  - French comment on article: A novel hemostatic powder for upper gastrointestinal
      bleeding: a multicenter study (the "GRAPHE" registry).

PMID- 27894143
TI  - French comment on article: Radiofrequency ablation for the management of occluded
      biliary metal stents.

PMID- 27894144
TI  - French comment on article: Trends in quality of screening colonoscopy in Austria.

PMID- 27894145
TI  - French comment on article: Impact of an automated system for endocytoscopic
      diagnosis of small colorectal lesions: an international web-based study.

PMID- 27894146
TI  - Variables Associated with Chondral and Meniscal Injuries in Anterior Cruciate
      Ligament Surgery.
AB  - This article aims to evaluate factors associated with chondral and meniscal
      lesions in primary and revision anterior cruciate ligament (ACL) reconstructions.
      ACL reconstructions from 2001 to 2008 at a single institution were
      retrospectively analyzed. Logistic regression was used to estimate the
      association between chondral and meniscal injuries and age, gender, tear
      chronicity, additional ligamentous injuries, sport type, and participation level.
      Of the 3,040 ACL reconstructions analyzed, 90.4% were primary reconstructions and
      9.6% were revisions. Meniscal injuries were significantly lower in the revision
      group (44.0 vs. 51.9%; p = 0.01), while chondral injuries were significantly
      higher in the revision group (39.9 vs. 24.0%; p < 0.0001). Inspection of the
      small subgroup (n = 85) receiving both primary and revision ACL surgery at our
      center indicated that meniscal injuries at revision were evenly split between
      menisci with and without previous repairs, whereas the vast majority of Grade III
      and IV chondral lesions were new. More patients presented for surgery later in
      the revision group than in the primary group (56.5 vs. 35.3%; p < 0.0001). Male
      gender, primary reconstruction, and short interval (less than 2 weeks) between
      injury and surgery were associated with increased likelihood of meniscus tear.
      Age (greater than 22 years) and long interval (greater than 6 weeks) between
      injury to surgery and higher sport activity level were associated with chondral
      lesions. Revision ACL reconstructions are associated with a higher proportion of
      chondral lesions and a lower proportion of meniscal tears. Early primary and
      revision ACL construction is recommended to reduce the probability of chondral
      lesions.

PMID- 27894147
TI  - Reliability, Concurrent Validity, and Minimal Detectable Change for iPhone
      Goniometer App in Assessing Knee Range of Motion.
AB  - Much of the published works assessing the reliability of smartphone goniometer
      apps (SG) have poor generalizability since the reliability was assessed in
      healthy subjects. No research has established the values for standard error of
      measurement (SEM) or minimal detectable change (MDC) which have greater clinical
      utility to contextualize the range of motion (ROM) assessed using the SG. This
      research examined the test-retest reproducibility, concurrent validity, SEM, and
      MDC values for the iPhone goniometer app (i-Goni; June Software Inc., v.1.1, San
      Francisco, CA) in assessing knee ROM in patients with knee osteoarthritis or
      those after total knee replacement. A total of 60 participants underwent data
      collection which included the assessment of active knee ROM using the i-Goni and
      the universal goniometer (UG; EZ Read Jamar Goniometer, Patterson Medical,
      Warrenville, IL), knee muscle strength, and assessment of pain and lower
      extremity disability using quadruple numeric pain rating scale (Q-NPRS) and lower
      extremity functional scale (LEFS), respectively. Intraclass correlation
      coefficients (ICCs) were calculated to assess the reproducibility of the knee ROM
      assessed using the i-Goni and UG. Bland and Altman technique examined the
      agreement between these knee ROM. The SEM and MDC values were calculated for i
      Goni assessed knee ROM to characterize the error in a single score and the index
      of true change, respectively. Pearson correlation coefficient examined concurrent
      relationships between the i-Goni and other measures. The ICC values for the knee
      flexion/extension ROM were superior for i-Goni (0.97/0.94) compared with the UG
      (0.95/0.87). The SEM values were smaller for i-Goni assessed knee
      flexion/extension (2.72/1.18 degrees) compared with UG assessed knee
      flexion/extension (3.41/1.62 degrees). Similarly, the MDC values were smaller for
      both these ROM for the i-Goni (6.3 and 2.72 degrees) suggesting smaller change
      required to infer true change in knee ROM. The i-Goni assessed knee ROM showed
      expected concurrent relationships with UG, knee muscle strength, Q-NPRS, and the
      LEFS. In conclusion, the i-Goni demonstrated superior reproducibility with
      smaller measurement error compared with UG in assessing knee ROM in the recruited
      cohort. Future research can expand the inquiry for assessing the reliability of
      the i-Goni to other joints.

PMID- 27894148
TI  - Catastrophic Failure of Regenerex Tibial Components: A Case Series.
AB  - The aim of this study was to analyze short-term metal failures in well-placed
      Signature-guided Regenerex (Zimmer Biomet, Warsaw, IN) tibial components in a
      limited patient series. A retrospective, consecutive, nonrandomized, unblinded
      study from a limited cohort of young active osteoarthritis patients was
      conducted. All cases received a Regenerex tibial component which we evaluated for
      metal failure. Patients met the then current indications from the Center for
      Medicare and Medicaid Services Guidelines for knee replacement. Age, body mass
      index (BMI),and gender were compared between Regenerex and concurrent non
      Regenerex knee arthroplasties. We identified a 4.7% (2 of 43) fracture rate in
      our Regenerex tibia replacements. Fractures occurred after 17 and 37 months, with
      a mean follow-up of 65 months (44-77). No statistical difference was seen in age
      or BMI between the fracture and nonfracture groups. Regenerex compared with
      standard arthroplasty patients were younger and predominantly male. Our inability
      to identify our fractures in the Food and Drug Administration (FDA) reporting
      site is concerning, suggesting additional cases may be unreported. A short-term
      Regenerex tibial fracture rate of 4.7% is unacceptably high. Inability to
      identify our fractures on the FDA Web site is a system failure, suggesting
      additional component fractures may be unreported.

PMID- 27894149
TI  - 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-Glucoside Attenuates
      Ischemia/Reperfusion-Induced Brain Injury in Rats by Promoting Angiogenesis.
AB  - Cerebral ischemia can cause brain infarcts, which are difficult to recover due to
      poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucoside is a
      natural polyphenol, has antioxidant and anti-inflammatory activity, and can
      protect from ischemic neuronal injury. However, little is known about the effect
      of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside on brain microcirculation
      after stroke. This study aimed at investigating the influence of 2,3,5,4'
      tetrahydroxystilbene-2-O-beta-D-glucoside on brain lesions and angiogenesis after
      stroke. Sprague-Dawley rats were subjected to right middle cerebral artery
      occlusion and treated with vehicle, nimodipine, or different doses of 2,3,5,4'
      tetrahydroxystilbene-2-O-beta-D-glucoside daily beginning at 6 h post-middle
      cerebral artery occlusion for 14 days. The volume of cerebral infarcts, degree of
      neurological dysfunction, and level of microvessel density were determined
      longitudinally. The levels of vascular endothelial growth factor, angiopoietin 1,
      and angiopoietin receptor-2 expression in the brain lesions were characterized by
      immunohistochemistry and Western blot assays at 14 days post-middle cerebral
      artery occlusion. We found that 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D
      glucoside significantly promoted postoperative recovery in rats by minimizing the
      volume of cerebral infarcts and improving neurological dysfunction in a dose- and
      time-dependent manner. Additionally, 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D
      glucoside significantly increased the microvessel density in the brain and
      upregulated CD31 expression in ischemic penumbra, relative to that in the
      control. Finally, treatment with 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D
      glucoside significantly upregulated the relative levels of vascular endothelial
      growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the
      brain lesions of rats. Therefore, these data indicated that 2,3,5,4'
      tetrahydroxystilbene-2-O-beta-D-glucoside treatment promoted angiogenesis and
      recovery from ischemia/reperfusion-induced brain injury in rats.

PMID- 27894150
TI  - Spatial Approach of Perinatal Mortality in Sao Paulo State, 2003-2012.
AB  - Objectives To identifying spatial patterns in the distribution of perinatal
      mortality in the state of Sao Paulo from 2003 to 2012. Methods An ecological and
      exploratory study with data on perinatal mortality rates of every thousand live
      births, which were registered on the digital database containing 645
      municipalities in the state of Sao Paulo within the periods of 2003 to 2007 and
      2008 to 2012. The spatial analysis provided Moran's index (MI) and thematic maps
      of rates, and the Moran maps of both periods were drawn. The average rates were
      compared by Student's t test. The TerraView 4.2.2 software (INPE, S. Jose dos
      Campos, Brazil) was also used. Results There were 49,485 perinatal deaths during
      the first period, at a rate of 17.90 deaths/1,000 live births (standard deviation
      [SD] = 7.0; MI = 0.14; p = 0.01), and 44,582 perinatal deaths during the second
      period, at a rate of 16.40 deaths/1,000 live births (SD = 11.14; MI = 0.04; p =
      0.03). These rates are statistically different (p < 0.01). There was a decrease
      in these rates in 413 municipalities when comparing the two periods. The Moran
      map has identified 35 municipalities that require special attention, which are
      located in the Eastern, Southwestern, Western and Northwestern regions of Sao
      Paulo state. Conclusion The study provides municipal managers with subsidies so
      they can minimize these rates by implementing public policies and taking better
      care of pregnant women and newborns.

PMID- 27894151
TI  - Value of the Ultrasound in the Study of Ovarian Reserve for Prediction of Oocyte
      Recovery.
AB  - Purpose To identify which methods used in the assessment of the ovarian reserve
      are exclusive or complementary to identify the best response to follicle
      development. Methods Retrospective cohort study, involving patients undergoing
      assisted reproduction treatment at the Instituto de Medicina Reprodutiva e Fetal,
      from April 2009 to July 2014. Age, biochemical tests, and ultrasound were
      assessed. The data were analyzed to predict the follicular development and the
      relation between them, using, for statistical analysis, Statistical Package for
      Social Sciences software. Results Out of the 293 couples included, 50.2%
      presented infertility by ovarian factor. Considering the age as the main
      variable, a significant negative correlation with the volume of both ovaries was
      observed (right ovary, r = 0.21; left ovary, r = -0.22; both p < 0.0001), and
      with the antral follicle count (right ovary, r = -0.38; left ovary, r = -0.47;
      both p < 0.0001). Considering the antral follicle count as the main variable, a
      significant positive correlation with the total recruited oocytes was observed.
      When we correlated the antral follicle count with the recruited follicles larger
      than 18 mm, we observed that, with a cutoff of 12 antral follicles, there is a
      positive predictive value of 99%, and an area under the ROC curve of 0.76.
      Conclusion We concluded from our study that age and antral follicle count are
      effective predictors of ovarian response in cycles of assisted reproduction. The
      ovarian volume, as well as the anti-Mullerian hormone dosage, seem to be adequate
      markers of the ovarian reserve.

PMID- 27894153
TI  - Painless Indocyanine Green Lymphography.

PMID- 27894152
TI  - Surgical Decompression in the Treatment of Diabetic Peripheral Neuropathy: A
      Systematic Review and Meta-analysis.
AB  - Background Over the last decade, surgical decompression procedures have been
      commonly used in the treatment of diabetic peripheral neuropathy. However, the
      effectiveness of them remains to be proved. Methods A comprehensive literature
      search of databases including PubMed-Medline, Ovid-EMBASE, and Cochrane Library
      was performed to collect the related literatures. The Medical Subject Headings
      used were "diabetic neuropathy," "surgical decompression," and "outcomes." The
      methodological index for nonrandomized studies was adopted for assessing the
      studies included in this review. Analyses were performed with Review Manager
      (Version 5.3, Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration,
      2014). Results A total of 12 literatures (including 8 prospective and 4
      retrospective) encompassing 1,825 patients with DPN were included in the final
      analysis. Only one literature was identified as a randomized controlled trial.
      The remaining 11 literatures were observational studies; 7 of them were
      classified as upper-extremity nerve decompression group and 4 of them were
      classified as lower-extremity nerve decompression group. Meta-analysis shows that
      Boston questionnaire symptom severity and functional status of upper extremities,
      and distal motor latency and sensory conduction velocity of median nerve of DPN
      patients are significantly improved after carpal tunnel release. Besides, visual
      analog scale and two-point discrimination are considered clinically and
      statistically significant in lower extremities after operation. Conclusions The
      findings from our review have shown the efficacy of surgical decompression
      procedures in relieving the neurologic symptoms and restoring the sensory
      deficits in DPN patients. As there are few high-quality randomized controlled
      trials or well-designed prospective studies, more data are needed to elucidate
      the role of surgical procedures for DPN treatment in the future.

PMID- 27894154
TI  - Perfusion Controlled Mobilization after Lower Extremity Free Flaps-Pushing the
      Limits of Time and Intensity.
AB  - Background The current standard to gradually adapt the fragile perfusion in lower
      extremity free flaps to an upright posture is the dangling maneuver. This type of
      flap training neither fits the orthostatic target load of an upright posture, nor
      does it assist in mobilizing the patients effectively. In this study, we
      quantitatively analyzed training effects of an early and full mobilization on
      flap perfusion. Methods A total of 15 patients with gracilis flaps for distal
      lower extremity reconstruction were included. Flap training was performed daily
      by mobilizing the patients on a tilt table into a fully upright posture for 5
      minutes between the third and fifth postop days (PODs). Changes in micro- and
      macrocirculation were analyzed by laser Doppler flowmetry, remission
      spectroscopy, and an implanted Doppler probe. Results All flaps healed without
      complications. Yet, in three patients, the increased orthostatic load required an
      adjustment of the training duration due to a critical blood flow. The others
      showed an increasing compensation in the microcirculation. When tilting the
      patients, blood flow and oxygen saturation dropped significantly less on POD5
      than on POD3. Furthermore, a significant increase of the blood flow was noted
      after an initial decrease during the mobilization on all days. An increasing
      compensation in the macrocirculation could not be determined. Conclusion Full
      mobilization of patients with lower extremity free flaps can be performed safely
      under perfusion monitoring, already starting on POD3. Additionally, monitoring
      allows a consideration of the individual orthostatic competence and therefore,
      exploitation of the maximum mobilization potential.

PMID- 27894155
TI  - Increased Lower Extremity Venous Stasis May Contribute to Deep Venous Thrombosis
      Formation after Microsurgical Breast Reconstruction-An Ultrasonographic Study.
AB  - Background Despite guideline-compliant prophylaxis, an increased rate of deep
      venous thrombosis (DVT) formation has been reported following autologous versus
      implant-based breast reconstruction. We hypothesized that tight abdominal fascia
      closure might decrease lower extremity venous return and promote venous stasis.
      Methods An observational crossover study of patients who underwent autologous
      breast reconstruction using transverse rectus abdominis musculocutaneous/deep
      inferior epigastric artery perforator flaps was conducted. Ultrasonographic
      measurements of the left common femoral vein (CFV) and right internal jugular
      vein (IJV) were performed preoperatively, in the postanesthesia care unit, and on
      postoperative day (POD) 1. Parameters of interest included vessel diameter,
      circumference, area, and maximum flow velocity. Results Eighteen patients with a
      mean age and body mass index of 52.7 years (range, 29-76 years) and 31.3 kg/m2
      (range, 21.9-43.4 kg/m2) were included, respectively. A 29.8% increase in CFV
      diameter was observed on POD 1 (p < 0.0001). Similarly, a 24.3 and 69.9% increase
      in CFV circumference (p = 0.0007) and area (p < 0.0001) were noted, respectively.
      These correlated with a 28.4% decrease in maximum flow velocity in the CFV (p =
      0.0001). Of note, none of these parameters displayed significant changes for the
      IJV, thus indicating that observed changes in the CFV were not the result of
      changes in perioperative fluid status. Conclusion Postoperative changes observed
      in the CFV reflect increased lower extremity venous stasis after microsurgical
      breast reconstruction and may contribute to postoperative DVT formation.

PMID- 27894156
TI  - Mitral valve repair using an autologous pericardial strip in infants and young
      children.
AB  - We have modified the mitral repair technique in infants and small children by
      using autologous pericardial strips to treat mitral regurgitation resulting from
      a dilated mitral annulus. Our results demonstrate that this technique maintains
      stability and flexibility of the mitral annulus and decreases the risk of mitral
      stenosis.

PMID- 27894157
TI  - Brief Report: Relationship Between Serum Infliximab Concentrations and Risk of
      Infections in Patients Treated for Spondyloarthritis.
AB  - OBJECTIVE: Tumor necrosis factor inhibitors are effective in reducing
      inflammation in rheumatic diseases but increase the risk of infections. This
      study was undertaken to investigate the relationship between the trough serum
      concentration of infliximab (IFX) and the risk of a first infection episode.
      METHODS: We retrospectively included all patients who started IFX treatment for
      an approved indication in our department. Patients were followed up based on
      recommended IFX infusion schedules. We studied the relationship between the
      occurrence of a first infection episode requiring hospitalization, anti-infection
      treatment, or IFX infusion deferral, and the last trough IFX concentration and
      mean of the last 3 trough IFX concentrations measured before the infection
      episode. RESULTS: Of the 201 patients included in the analysis, 173 had
      spondyloarthritis (SpA). The SpA patients had a mean +/- SD age of 46 +/- 12
      years and a disease duration of 6.2 +/- 6.1 years. During a median follow-up of
      1.1 year, 87 SpA patients had at least 1 infection episode. Using Cox models, we
      found that the probability of survival without infection was significantly higher
      in patients with a mean of the last 3 trough IFX concentrations lower than the
      median (<11.3 mg/liter) than in patients with a mean concentration greater than
      the median (P = 0.048 by log-rank test). Glucocorticoid use and IFX concentration
      were significantly associated with the risk of a first infection episode in the
      multivariable analysis (P = 0.004 for both). The risk of infection episode was
      significantly increased in the highest quartile of the mean of the last 3 trough
      IFX concentrations (>20.3 mg/liter) (hazard ratio 2.65 [95% confidence interval
      1.14-6.14], P = 0.023). CONCLUSION: Our findings indicate that a high IFX
      concentration is correlated with a higher risk of a first infection episode, but
      these findings need to be replicated in further prospective studies.

PMID- 27894158
TI  - Craving behavioral intervention for internet gaming disorder: remediation of
      functional connectivity of the ventral striatum.
AB  - Psychobehavioral intervention is an effective treatment of Internet addiction,
      including Internet gaming disorder (IGD). However, the neural mechanisms
      underlying its efficacy remain unclear. Cortical-ventral striatum (VS) circuitry
      is a common target of psychobehavioral interventions in drug addiction, and
      cortical-VS dysfunction has been reported in IGD; hence, the primary aim of the
      study was to investigate how the VS circuitry responds to psychobehavioral
      interventions in IGD. In a cross-sectional study, we examined resting-state
      functional connectivity of the VS in 74 IGD subjects (IGDs) and 41 healthy
      controls (HCs). In a follow-up craving behavioral intervention (CBI) study, of
      the 74 IGD subjects, 20 IGD subjects received CBI (CBI+) and 16 IGD subjects did
      not (CBI-). All participants were scanned twice with similar time interval to
      assess the effects of CBI. IGD subjects showed greater resting-state functional
      connectivity of the VS to left inferior parietal lobule (lIPL), right inferior
      frontal gyrus and left middle frontal gyrus, in positive association with the
      severity of IGD. Moreover, compared with CBI-, CBI+ showed significantly greater
      decrease in VS-lIPL connectivity, along with amelioration in addiction severity
      following the intervention. These findings demonstrated that functional
      connectivity between VS and lIPL, each presumably mediating gaming craving and
      attentional bias, may be a potential biomarker of the efficacy of
      psychobehavioral intervention. These results also suggested that non-invasive
      techniques such as transcranial magnetic or direct current stimulation targeting
      the VS-IPL circuitry may be used in the treatment of Internet gaming disorders.

PMID- 27894159
TI  - Phylogenetic and ecological diversity of apusomonads, a lineage of deep-branching
      eukaryotes.
AB  - Apusomonads are a mysterious group of heterotrophic gliding biflagellates
      branching deeply in the eukaryotic tree of life as sister group to opisthokonts
      (including animals, fungi, and a variety of unicellular protists). Despite their
      evolutionary interest, their diversity and ecology remain largely unknown, with
      very few described species and environmental sequences in databases. Most
      environmental 18S rRNA gene-based studies generally fail to identify apusomonad
      sequences, which might be due to primer bias, low abundance, and/or to the fact
      that their biotopes remain poorly explored. We have carried out an extensive
      search of 18S rRNA genes using an apusomonad-specific primer in a wide variety of
      ecosystems. Our study significantly broadens the diversity of apusomonads showing
      that, despite being mostly rare protists, they often dwell in freshwater and
      marine benthic environments, generally associated with low-oxygen concentrations.
      Apusomonads have been identified in environments across a wide salinity range.
      Some operational taxonomic units (OTUs), occurring in both marine and freshwater
      ecosystems, seem truly euryhaline, indicating that members of this deep-branching
      lineage easily cross such ecological barriers.

PMID- 27894160
TI  - Cue-induced nicotine-seeking behavior after withdrawal with or without extinction
      in rats.
AB  - Exposure to smoking-associated environmental cues during smoke cessation elicits
      self-reported urge/craving to smoke, which precipitates relapse even after
      prolonged abstinence. Incubation of cue-induced cigarettes craving during
      abstinence has been observed in human smokers recently. The present studies
      assessed cue-induced nicotine-seeking behavior under different withdrawal
      conditions in rats with a history of nicotine self-administration. We found that
      non-reinforced operant responding during cue-induced nicotine seeking after
      different periods of withdrawal from nicotine exhibited an inverted U-shaped
      curve, with higher levels of responding after 7-21 days of withdrawal than those
      after 1-day withdrawal. Cue-induced nicotine-seeking responding is long lasting
      and persists even after 42 days of forced withdrawal in the home cages.
      Interestingly, repeated testing of cue-induced nicotine seeking at different
      withdrawal time points (1, 7, 14, 21 and 42 days) in the same individual
      alleviated responding as compared with the between-subjects assessment.
      Furthermore, extinction training during nicotine withdrawal significantly
      decreased cue-induced reinstatement of nicotine-seeking behavior. Together,
      profound time-dependent incubation of cue-induced craving in nicotine-experienced
      rats were observed. In addition, repeated cue exposure or extinction training
      decreases cue-induced craving. The demonstration of incubation of nicotine
      craving phenomenon in both rat and human studies provides support for the
      translational potential of therapeutic targets for relapse uncovered through
      mechanism studies in rats.

PMID- 27894161
TI  - Climate and season: the effects on ophthalmic diseases.
AB  - Seasonal changes and climate have a significant impact on human health. Diseases
      influenced by temperature and climate conditions are likely to undergo dynamic
      pattern shifts with consequent impact on human health. A number of infectious and
      non-infectious ophthalmic diseases are influenced by temperature and seasonality.
      Awareness of this is important from public and global health perspective in
      addition to resource allocation strategies. We examine the evidence for a
      seasonal pattern to ophthalmic diseases and assess the possible impact of climate
      change.

PMID- 27894162
TI  - Partitioning the effects of mating and nuptial feeding on the microbiome in gift
      giving insects.
AB  - Mating is a ubiquitous social interaction with the potential to influence the
      microbiome by facilitating transmission, modifying host physiology, and in
      species where males donate nuptial gifts to females, altering diet. We
      manipulated mating and nuptial gift consumption in two insects that differ in
      nuptial gift size, the Mormon cricket Anabrus simplex and the decorated cricket
      Gryllodes sigillatus, with the expectation that larger gifts are more likely to
      affect the gut microbiome. Surprisingly, mating, but not nuptial gift
      consumption, affected the structure of bacterial communities in the gut, and only
      in Mormon crickets. The change in structure was due to a precipitous drop in the
      abundance of lactic-acid bacteria in unmated females, a taxon known for their
      beneficial effects on nutrition and immunity. Mating did not affect phenoloxidase
      or lysozyme-like antibacterial activity in either species, suggesting that any
      physiological response to mating on host-microbe interactions is decoupled from
      systemic immunity. Protein supplementation also did not affect the gut microbiome
      in decorated crickets, suggesting that insensitivity of gut microbes to dietary
      protein could contribute to the lack of an effect of nuptial gift consumption.
      Our study provides experimental evidence that sexual interactions can affect the
      microbiome and suggests mating can promote beneficial gut bacteria.

PMID- 27894163
TI  - Feature of amenorrhea in postoperative tamoxifen users with breast cancer.
AB  - OBJECTIVE: Tamoxifen has been used to prevent the recurrence of breast cancer.
      However, tamoxifen-users frequently experience amenorrhea and it can be confused
      from that caused by other hormonal abnormalities. In amenorrheic patients without
      breast cancer, clinicians usually measure the sex hormone levels that are known
      to be associated with ovarian or menstrual function. This study aimed to
      investigate the feature of female sex hormones in premenopausal breast cancer
      patients undergoing tamoxifen treatment. METHODS: The medical records of fifty
      nine premenopausal breast cancer patients who underwent tamoxifen treatment were
      reviewed retrospectively. The study population consisted of amenorrheic patients
      (n=36) and patients with menstruation (n=23). Serum hormone levels were measured
      either specifically between cycle days 2 and 5 in menstruating patients or at any
      time in amenorrheic participants. RESULTS: Serum levels of lutenizing hormone and
      estradiol were not statistically different according to the presence of
      menstruation. Serum follicle stimulating hormone level was significantly higher
      in amenorrheic patients (8.1+/-5.7 mIU/mL) than those in menstruating subjects
      (5.1+/-2.2 mIU/mL) (p=0.01). Serum concentration of thyroid stimulating hormone
      was lower in patients with amenorrhea (1.5+/-0.9 vs. 2.3+/-2.2 MUIU/mL, p=0.04),
      although the prevalence of hypo- or hyperthyroidism was not different according
      to the pattern of menstruation. CONCLUSION: Menstruation status and hormone
      levels can be influenced by tamoxifen use in reproductive age breast cancer
      patients. Physicians should be attentive to the alteration of pituitary hormone
      levels in addition to sex steroid hormones in this population.

PMID- 27894164
TI  - Preoperative CA125 and fibrinogen in patients with endometrial cancer: a risk
      model for predicting lymphovascular space invasion.
AB  - OBJECTIVE: The aim of this study was to build a model to predict the risk of
      lymphovascular space invasion (LVSI) in women with endometrial cancer (EC).
      METHODS: From December 2010 to June 2013, 211 patients with EC undergoing surgery
      at Shanghai First Maternity and Infant Hospital were enrolled in this
      retrospective study. Those patients were divided into a positive LVSI group and a
      negative LVSI group. The clinical and pathological characteristics were compared
      between the two groups; logistic regression was used to explore risk factors
      associated with LVSI occurrence. The threshold values of significant factors were
      calculated to build a risk model and predict LVSI. RESULTS: There were 190
      patients who were negative for LVSI and 21 patients were positive for LVSI out of
      211 patients with EC. It was found that tumor grade, depth of myometrial
      invasion, number of pelvic lymph nodes, and International Federation of
      Gynecology and Obstetrics (FIGO) stage (p<0.05) were associated with LVSI
      occurrence. However, cervical involvement and age (p>0.05) were not associated
      with LVSI. Receiver operating characteristic (ROC) curves revealed that the
      threshold values of the following factors were correlated with positive LVSI:
      28.1 U/mL of CA19-9, 21.2 U/mL of CA125, 2.58 mg/dL of fibrinogen (Fn), 1.84 U/mL
      of carcinoembryonic antigen (CEA) and (6.35*109)/L of white blood cell (WBC).
      Logistic regression analysis indicated that CA125 >=21.2 (p=0.032) and Fn >=2.58
      mg/dL (p=0.014) were significantly associated with LVSI. CONCLUSION: Positive
      LVSI could be predicted by CA125 >=21.2 U/mL and Fn >=2.58 mg/dL in women with
      EC. It could help gynecologists better adapt surgical staging and adjuvant
      therapies.

PMID- 27894166
TI  - The detection of sentinel lymph nodes in laparoscopic surgery for uterine
      cervical cancer using 99m-technetium-tin colloid, indocyanine green, and blue
      dye.
AB  - OBJECTIVE: Our objective was to determine the feasibility and detection rates and
      clarify the most effective combination of injected tracer types for sentinel
      lymph node (SLN) mapping in uterine cervical cancer in patients who have
      undergone laparoscopic surgery or neoadjuvant chemotherapy (NAC). METHODS: A
      total of 119 patients with cervical cancer underwent SLN biopsy at radical
      hysterectomy using three types of tracers. The various factors related to side
      specific detection rate, sensitivity, and false negative (FN) rate were analyzed.
      RESULTS: The SLN detection rates using 99m-technetium ((99m)Tc)-tin colloid,
      indigo carmine, and indocyanine green (ICG) were 85.8%, 20.2%, and 61.6%,
      respectively. The patients with >=2-cm-diameter tumors and those who received NAC
      had lower detection rates than those with <2-cm-diameter tumors (75.7% vs. 91.5%,
      p<0.01) and those who did not receive NAC (67.9% vs. 86.3%, p<0.01),
      respectively. Laparoscopic procedures had a higher detection rate than laparotomy
      (100.0% vs. 77.1%, p<0.01). No factors significantly affected the sensitivity;
      however, the patients with >=2-cm-diameter tumors (86.0% vs. 1.4%, p<0.01), NAC
      (19.4% vs. 2.2%, p<0.01), and those who underwent laparotomy (7.4% vs. 0%,
      p<0.01) had an unfavorable FN rate. CONCLUSION: Among the examined tracers,
      (99m)Tc had the highest detection of SLN mapping in patients with uterine
      cervical cancer. Patients with local advanced cervical cancer with/without NAC
      treatment might be unsuited for SLN mapping. SLN mapping is feasible and results
      in an excellent detection rate in patients with <2-cm-diameter cervical cancer.
      Laparoscopic surgery is the best procedure for SLN detection in patients with
      early-stage disease.

PMID- 27894169
TI  - The gate-keeping role of surgeons with regard to endometrial cancers in Lynch
      syndrome.

PMID- 27894168
TI  - Hysteroscopy in fertility-sparing management for early endometrial cancer: a
      double-edged sword.

PMID- 27894165
TI  - Practice guidelines for management of uterine corpus cancer in Korea: a Korean
      Society of Gynecologic Oncology Consensus Statement.
AB  - Clinical practice guidelines for gynecologic cancers have been developed by many
      organizations. Although these guidelines have much in common in terms of the
      practice of standard of care for uterine corpus cancer, practice guidelines that
      reflect the characteristics of patients and healthcare and insurance systems are
      needed for each country. The Korean Society of Gynecologic Oncology (KSGO)
      published the first edition of practice guidelines for gynecologic cancer
      treatment in late 2006; the second edition was released in July 2010 as an
      evidence-based recommendation. The Guidelines Revision Committee was established
      in 2015 and decided to produce the third edition of the guidelines as an advanced
      form based on evidence-based medicine, considering up-to-date clinical trials and
      abundant qualified Korean data. These guidelines cover screening, surgery,
      adjuvant treatment, and advanced and recurrent disease with respect to
      endometrial carcinoma and uterine sarcoma. The committee members and many
      gynecologic oncologists derived key questions from the discussion, and a number
      of relevant scientific literatures were reviewed in advance. Recommendations for
      each specific question were developed by the consensus conference, and they are
      summarized here, together with other details. The objective of these practice
      guidelines is to establish standard policies on issues in clinical areas related
      to the management of uterine corpus cancer based on the findings in published
      papers to date and the consensus of experts as a KSGO Consensus Statement.

PMID- 27894167
TI  - Salinomycin reduces stemness and induces apoptosis on human ovarian cancer stem
      cell.
AB  - OBJECTIVE: Cancer stem cells (CSCs) represent a subpopulation of undifferentiated
      tumorigenic cells thought to be responsible for tumor initiation, maintenance,
      drug resistance, and metastasis. The role of CSCs in drug resistance and relapse
      of cancers could significantly affect outcomes of ovarian cancer patient.
      Therefore, therapies that target CSCs could be a promising approach for ovarian
      cancer treatment. The antibiotic salinomycin has recently been shown to deplete
      CSCs. In this study, we evaluated the effect of salinomycin on ovarian cancer
      stem cells (OCSCs), both alone and in combination with paclitaxel (PTX). METHODS:
      The CD44+CD117+CSCs were obtained from the ascitic fluid of patients with
      epithelial ovarian cancer by using an immune magnetic-activated cell sorting
      system. OCSCs were treated with PTX and salinomycin either singly or in
      combination. Cell viability and apoptosis assays were performed and spheroid
      forming ability was measured. The expression of sex determining region Y-box 2
      (SOX2) and octamer-binding transcription factor 3/4 (OCT3/4) mRNA was determined
      using reverse transcription polymerase chain reaction, and protein expression was
      observed using western blot analysis. RESULTS: Treatment with salinomycin alone
      reduced the stemness marker expression and spheroid-forming ability of OCSCs.
      Treatment with PTX alone did not decrease the viability of OCSCs. Treatment with
      a combination of salinomycin decreased the viability of OCSCs and promoted cell
      apoptosis. The enhancement of combination treatment was achieved through the
      apoptosis as determined by annexin V/propidium iodide (PI) staining, caspase-3
      activity, and DNA fragmentation assay. CONCLUSION: Based on our findings,
      combining salinomycin with other anti-cancer therapeutic agents holds promise as
      an ovarian cancer treatment approach that can target OCSCs.

PMID- 27894170
TI  - High Tibial Osteotomy for Medial Knee Osteoarthritis.

PMID- 27894171
TI  - Diagnosis and Treatment of Discoid Meniscus.
AB  - There is a greater incidence of discoid meniscus in Asian countries than in
      Western countries, and bilateral discoid menisci are also common. The discoid
      meniscus may be a congenital anomaly, and genetics or family history may play a
      role in the development of discoid menisci. Because the histology of discoid
      meniscus is different from that of normal meniscus, it is prone to tearing.
      Individuals with a discoid meniscus can be asymptomatic or symptomatic.
      Asymptomatic discoid menisci do not require treatment. However, operative
      treatment is necessary if there are symptoms. Total meniscectomy leads to an
      increased risk of osteoarthritis. Therefore, total meniscectomy is generally
      reserved for rare unsalvageable cases. Partial meniscectomy (saucerization) with
      preservation of a stable peripheral rim combined with or without peripheral
      repair is effective, and good short-, mid-, and long-term clinical results have
      been reported.

PMID- 27894172
TI  - The SPECT/CT Evaluation of Compartmental Changes after Open Wedge High Tibial
      Osteotomy.
AB  - Purpose: The purpose of this study was to evaluate compartmental changes using
      combined single-photon emission computerized tomography and conventional
      computerized tomography (SPECT/CT) after open wedge high tibial osteotomy (OWHTO)
      for providing clinical guidance for proper correction. Materials and Methods:
      Analysis was performed using SPECT/CT from around 1 year after surgery on 22
      patients who underwent OWHTO. Postoperative mechanical axis was measured and
      classified into 3 groups: group I (varus), group II (0 degrees -3 degrees 
      valgus), and group III (>3 degrees  valgus). Patella location was evaluated using
      Blackburne-Peel (BP) ratio. On SPECT/CT, the knee joint was divided into medial,
      lateral, and patellofemoral compartments and the brighter signal was marked as a
      positive signal. Results: Increased signal activity in the medial compartment was
      observed in 12 cases. No correlation was observed between postoperative
      mechanical axis and medial signal increase. Lateral increased signal activity was
      observed in 3 cases, and as valgus degree increased, lateral compartment's signal
      activity increased. Increased signal activity of the patellofemoral joint was
      observed in 7 cases, and significant correlation was observed between changes in
      BP ratio and increased signal activity. Conclusions: For the treatment of medial
      osteoarthritis, OWHTO requires overcorrection that does not exceed 3 valgus. In
      addition, the possibility of a patellofemoral joint problem after OWHTO should be
      kept in mind.

PMID- 27894173
TI  - Open Wedge High Tibial Osteotomy and Combined Arthroscopic Surgery in Severe
      Medial Osteoarthritis and Varus Malalignment: Minimum 5-Year Results.
AB  - Purpose: To evaluate the radiologic and functional outcomes of medial open wedge
      high tibial osteotomy (HTO) combined with arthroscopic procedure in patients with
      medial osteoarthritis. Materials and Methods: From June 1996 to March 2010, 26
      patients (32 knees) who underwent medial open wedge osteotomy and arthroscopic
      operation for medial osteoarthritis were retrospectively reviewed. Measurements
      included hip-knee-ankle (HKA) angle, femorotibial angle, medial proximal tibial
      angle, posterior tibial slope angle, and Kellgren-Lawrence grade. Clinical
      evaluation was performed using Lysholm knee scoring scale and knee and function
      score of the American Knee Society. Results: Differences between the mean
      preoperative and postoperative measurements were significant in all angles
      including the HKA angle (-5.7 degrees  and +5.5 degrees ), femorotibial angle (
      1.9 degrees  and +9.8 degrees ), and medial proximal tibial angle (82.9 degrees 
      and 90.5 degrees ) (p<0.05). Mean Lysholm knee scoring scale was 63.6
      preoperatively and 88.7 at the last follow-up, mean Knee Society knee score was
      61.2 and 86.6, and mean function score was 59.3 and 87.2, respectively. All
      differences were significant (p<0.05). Conclusions: Medial open wedge HTO in
      combination with arthroscopic procedure is an effective treatment method for
      medial osteoarthritis to treat varus deformity and an intra-articular lesion.

PMID- 27894174
TI  - Modified Iliac Crest Reconstruction with Bone Cement for Reduction of Donor Site
      Pain and Morbidity after Open Wedge High Tibial Osteotomy: A Prospective Study.
AB  - Purpose: This study was to determine the efficacy of iliac crest reconstruction
      using bone cement in reducing pain and morbidity at the donor site in patients
      undergoing open wedge high tibial osteotomy (OWHTO) with tricortical iliac crest
      autologous graft. Materials and Methods: Thirty-three patients who underwent
      iliac crest reconstruction using polymethyl methacrylate (PMMA) bone cement
      (group A) and thirty patients who had no iliac crest reconstruction (group B)
      were enrolled in this study. All patients were evaluated for pain and functional
      disability related to graft harvesting using the pain and functional visual
      analogue scale (VAS) score during hospital stay and at 6 weeks, 3 months, and 6
      months postoperatively. Results: There was significant difference between the two
      groups in terms of pain and function. The pain VAS score was significantly lower
      in group A than group B during the first 2 weeks postoperatively (p=0.04) and the
      functional VAS score was also significantly lower in group A during the first 2
      weeks postoperatively (p<0.001) in terms of breathing, sitting up from the supine
      position, and standing up with crutches from the sitting position. Conclusions:
      Iliac crest donor site reconstruction using PMMA bone cement in patients
      undergoing OWHTO significantly decreased pain and improved function during the
      first 2 weeks postoperatively when compared to patients who underwent OWHTO
      without iliac crest reconstruction.

PMID- 27894175
TI  - Comparison of Cable Method and Miniaci Method Using Picture Archiving and
      Communication System in Preoperative Planning for Open Wedge High Tibial
      Osteotomy.
AB  - Purpose: The purpose was to compare the accuracy of Miniaci method using picture
      archiving and communication system (PACS) with a cable method in high tibial
      osteotomy (HTO). Materials and Methods: This study analyzed 47 patients (52
      knees) with varus deformity and medial osteoarthritis. From 2007 to 2013,
      patients underwent HTO using either a cable method (20 knees) or Miniaci method
      based on a PACS image (32 knees). In the cable method, the 62.5% point of the
      mediolateral tibial plateau width was located using an electrocautery cord under
      fluoroscopy (cable group). The Miniaci method used preoperative radiographs to
      shift the weight bearing axis (PACS group). Full-length lower limb radiographs
      obtained preoperatively and at the sixth postoperative week were used to compare
      the percentage of crossing point of the weight bearing line on the tibial plateau
      with respect to the medial border. Results: The weight bearing line on the tibial
      plateau was corrected from a preoperative 11.0+/-7.0% to a postoperative 47.2+/
      7.4% in the cable group and from 12.7+/-4.9% to 59.5+/-5.3% in the PACS group.
      The mechanical femorotibial angle was corrected from varus 8.9+/-3.7 degrees  to
      valgus 0.3+/-4.0 degrees  in the cable group and from varus 9.0+/-3.3 degrees  to
      valgus 2.9+/-2.6 degrees  in the PACS group. Conclusions: In HTO, correction
      based on the Miniaci method using a PACS was more accurate than correction using
      the cable method.

PMID- 27894176
TI  - Complications and Short-Term Outcomes of Medial Opening Wedge High Tibial
      Osteotomy Using a Locking Plate for Medial Osteoarthritis of the Knee.
AB  - Purpose: The purpose of this study was to investigate complications and
      radiologic and clinical outcomes of medial opening wedge high tibial osteotomy
      (MOWHTO) using a locking plate. Materials and Methods: This study reviewed 167
      patients who were treated with MOWHTO using a locking plate from May 2012 to June
      2014. Patients without complications were classified into group 1 and those with
      complications into group 2. Medical records, operative notes, and radiographs
      were retrospectively reviewed to identify complications. Clinically, Oxford Knee
      score and Knee Injury and Osteoarthritis Outcome score (KOOS) were evaluated.
      Results: Overall, complications were observed in 49 patients (29.3%). Minor
      complications included lateral cortex fracture (15.6%), neuropathy (3.6%),
      correction loss (2.4%), hematoma (2.4%), delayed union (2.4%), delayed wound
      healing (2.4%), postoperative stiffness (1.2%), hardware irritation (1.2%),
      tendinitis (1.2%), and hardware failure without associated symptoms (0.6%). Major
      complications included hardware failure with associated symptoms (0.6%), deep
      infection (0.6%), and nonunion (0.6%). At the first-year follow-up, there were no
      significant differences in radiologic measurements between groups 1 and 2. There
      were no significant differences in knee scores except for the KOOS pain score.
      Conclusions: Our data showed that almost all complications of the treatment were
      minor and the patients recovered without any problems. Most complications did not
      have a significant impact on radiologic and clinical outcomes.

PMID- 27894177
TI  - Variability of Measurement of Patellofemoral Indices with Knee Flexion and
      Quadriceps Contraction: An MRI-Based Anatomical Study.
AB  - Purpose: The purpose of this study was to investigate the impact of varying knee
      flexion and quadriceps activity on patellofemoral indices measured on magnetic
      resonance imaging (MRI). Materials and Methods: MRI of the knee was performed in
      20 patients for indications other than patellar or patellofemoral pathology.
      Axial and sagittal sequences were performed in full extension of the knee with
      the quadriceps relaxed, full extension of the knee with the quadriceps
      contracted, 30 degrees  flexion of the knee with the quadriceps relaxed, and 30
      degrees  flexion with the quadriceps contracted. Bisect offset, patella tilt
      angle, Insall-Salvati ratio and Caton-Deschamps index were measured. Results:
      With the knee flexed to 30 degrees  and quadriceps relaxed, the mean values of
      patellar tilt angle, bisect offset, Insall-Salvati ratio and Caton-Deschamps
      index were all within normal limits. With the knee extended and quadriceps
      contracted, the mean patellar tilt angle (normal value, <15 degrees ) was 14.6
      degrees  and the bisect offset (normal value, <65%) was 65%, while the Caton
      Deschamps index was 1.34 (normal range, 0.6 to 1.3). With the knee extended and
      quadriceps relaxed, the mean Caton-Deschamps index was 1.31. Conclusions: MRI
      scanning of the knee in extension with the quadriceps contracted leads to
      elevated patellofemoral indices. MRI taken with the knee in 30 degrees  of
      flexion allows more reliable assessment of the patellofemoral joint and minimises
      the confounding effect of quadriceps contraction.

PMID- 27894178
TI  - Comparison of Radiological Parameters between Normal and Patellar Dislocation
      Groups in Korean Population: A Rotational Profile CT-Based Study.
AB  - Purpose: Patellofemoral instability is a common cause of anterior knee pain in
      adolescents and young adults. Most normal and pathological values for diagnosing
      patellofemoral instability are based on Western literature. We conducted this
      radiological study to determine normal values for different patellofemoral
      parameters in a Korean population and to evaluate their usefulness in diagnosis.
      Materials and Methods: We retrospectively reviewed the rotational profile
      computerized tomography (CT) scans of the patellar dislocation and control
      groups. Trochlear, patellar, rotational profile, and trochleo-patellar alignment
      parameters were compared between the groups. Receiver operating characteristic
      curves were drawn for significant parameters, and sensitivity and specificity
      were calculated for the cut-off values. Results: There were 48 patients in the
      patellar dislocation group and 87 patients in the control group. In the control
      group and patellar dislocation group, the mean sulcus angle was 132.5 degrees 
      and 143.3 degrees , respectively, trochlear depth was 6.04 mm and 3.6 mm, bisect
      offset was 56.4% and 99.9%, lateral patellar tilting was 9.8 degrees  and 19.2
      degrees , patellar facet asymmetry was 63.5% and 45.16%, and the tibial
      tuberosity-trochlear groove (TT-TG) distance was 10.91 mm and 27.16 mm,
      respectively. Conclusions: The trochlear depth, bisect offset, patella tilting,
      and TT-TG distance were parameters that significantly contributed to patellar
      instability. Rotational profile CT can be considered a good diagnostic tool to
      assess all these parameters that help to identify anatomical aberration resulting
      in patellofemoral instability, thereby helping in formulating the most effective
      treatment plan.

PMID- 27894179
TI  - Availability of Total Knee Arthroplasty Implants for Metal Hypersensitivity
      Patients.
AB  - Purpose: To provide information on the type of "hypersensitivity-friendly"
      components available for primary total knee arthroplasty (TKA) in the current
      market. Materials and Methods: Implant manufactures were identified using the
      2013 National Joint Registries of the United Kingdom and Sweden and contacted to
      obtain information about the products they offer for patients with metal
      hypersensitivity. Results: Information on 23 TKA systems was provided by 13
      implant manufacturers. Of these, 15 systems had options suitable for metal
      hypersensitivity patients. Two types of "hypersensitivity-friendly" components
      were identified: 10 implants were cobalt chrome prostheses with a
      "hypersensitivity-friendly" outer coating and 5 implants were made entirely from
      non-cobalt chrome alloys. Conclusions: The results of this study suggest that
      several hypersensitivity TKA options exist, some of which provide the same
      designs and surgical techniques as the conventional implants. The information in
      this study can guide TKA surgeons in making informed choices about implants and
      identifying implants that could be examined in future controlled studies
      comparing outcomes between "hypersensitivity-friendly" and conventional implants.

PMID- 27894180
TI  - Causes of Failure of Anterior Cruciate Ligament Reconstruction and Revision
      Surgical Strategies.
AB  - Purpose: Long-term outcomes of anterior cruciate ligament (ACL) reconstruction
      are good or excellent; however, 0.7%-20% of patients suffer from recurrent
      instability due to graft failure. The purpose of this paper was to analyse
      failure aetiology and the possibilities of revision surgical strategies, with a
      description of our experience. We obtained optimal and good results in most of
      our patients. Materials and Methods: We retrospectively reviewed 42 patients who
      underwent revision surgery (43 revisions) due to relapsing instability after ACL
      reconstruction between 2006 and 2015. We used allografts in 39 cases and
      autografts in 4 cases. Results: The 85.7% of the patients obtained optimal
      results (normal knee; group A) and the 7.2% obtained good results (nearly normal
      knee; group B) according to the International Knee Documentation Committee score.
      The most frequent failure causes were traumatic events, non-anatomic tunnel
      placement, and lack of graft incorporation. Conclusions: A correct revision
      surgery requires accurate patient evaluation and knee imaging. Preoperative
      planning starts with the identification of the cause of failure of the primary
      reconstruction. Then, the most suitable procedure should be determined for each
      case. It is also important to accurately inform the patient of all the complexity
      of an ACL revision surgery even if it is a procedure with high rates of excellent
      and good outcomes.

PMID- 27894181
TI  - Total Knee Arthroplasty for Severe Flexion Contracture in Rheumatoid Arthritis
      Knees.
AB  - Flexion contracture deformities, as well as severe varus and valgus deformities
      of the knee joint, accompany osteoarthritis or rheumatoid arthritis (RA). In
      particular, severe flexion contracture deformity of the knee joint is often found
      in patients with RA, which renders them nonambulatory. This report describes a 26
      year-old female patient diagnosed with RA 10 years ago. She had chronic joint
      pain, severe flexion contracture, valgus deformity in both knees, and limited
      range of motion in both knees and became nonambulatory. She underwent a total
      knee arthroplasty (TKA) and serial casting and physical therapy to restore stable
      joint movement and correct knee joint deformity. Her pain was successfully
      relieved, and she was able to walk after surgery. Here, we report the excellent
      results of TKA in this RA patient with severe flexion contracture of both knees.

PMID- 27894182
TI  - Medial and Lateral Discoid Menisci of Both Knees.
AB  - Discoid menisci on both the medial and lateral sides are rare, and there are very
      few reports on cases involving both sides. We report a case of a 52-year-old
      female with medial and lateral discoid menisci in both knees. Arthroscopy
      revealed the lateral menisci of both knees were complete discoid menisci, and
      partial meniscectomy was performed. The medial menisci were incomplete discoid
      menisci, but there were no findings of abnormal mobility or injury; therefore,
      the medial menisci were observed without treatment. At six months
      postoperatively, her pain and range of motion restrictions disappeared.

PMID- 27894183
TI  - The effect of the SNAPPS (summarize, narrow, analyze, probe, plan, and select)
      method versus teacher-centered education on the clinical gynecology skills of
      midwifery students in Iran.
AB  - This study aimed to determine the effect of the SNAPPS (summarize, narrow,
      analyze, probe, plan, and select) method versus teacher-centered education on the
      clinical skills of midwifery students in Iran. In this clinical trial, 36
      midwifery students in their 4th year of education in 2015 were enrolled and
      divided into 6 groups, 3 groups for teacher-centered education and 3 groups for
      the SNAPPS method, with each group spending 10 days in the outpatient gynecology
      clinic. A questionnaire and a checklist were used to gather data. An independent
      t-test and chi-square test were used to analyze the data. Ability to gain the
      trust of the patient, verbal and nonverbal communication skills, history taking,
      preparation of the patient for gynecological examination, and diagnosis and
      treatment of common diseases were significantly better in the SNAPPS group
      compared to the teacher-centered education group (P<0.05). The SNAPPS education
      method can significantly improve the clinical skills of midwifery students in
      gynecology, in particular history taking, differential diagnosis, and treatment
      of common diseases.

PMID- 27894184
TI  - Australian medical students have fewer opportunities to do physical examination
      of peers of the opposite gender.
AB  - PURPOSE: Peer physical examination (PPE), by which junior medical students learn
      physical examination skills before practicing on patients, is a widely
      implemented and accepted part of medical curricula. However, the ethical
      implications of PPE have been debated, since issues including student gender
      impact on its acceptability. Research has previously demonstrated the phenomenon
      of 'attitude-behavior inconsistency' showing that students' predictions about
      their participation in PPE differ from what they actually do in practice. This
      study asks whether gender and student self-ratings of outlook affect engagement
      in PPE. METHODS: This study gathered data from students who had completed PPE
      with the objective of determining what factors have the greatest impact on the
      actual practice of PPE by students. Data were used to derive the number of
      opportunities students had to examine a peer, for various body parts. Respondent
      gender and self-ratings of outlook were recorded. RESULTS: Responses from 130
      students were analysed: 74 female (57%) and 56 male (43%). Students have fewer
      opportunities to examine peers of the opposite gender; this is statistically
      significant for all body parts when male students examine female peers.
      CONCLUSION: Gender is the factor of overriding importance on whether these peer
      interactions actually occur, such that students have fewer opportunities to
      examine peers of the opposite gender, particularly male students examining female
      peers. Student outlook has little impact. We speculate that the more acceptable
      PPE is to participants, paradoxically, the more complicated these interactions
      become, possibly with implications for future practice.

PMID- 27894185
TI  - Endoscopic Retrograde Cholangiopancreatography in Post Gastrectomy Patients.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) in post-gastrectomy
      patients with Billroth II (BII) reconstruction and Roux-en-Y (RY) reconstruction
      presents a challenge to therapeutic endoscopists. Major difficulties, including
      intubation to the ampulla of Vater, selective cannulation, and ampullary
      intervention, must be overcome in these patients. Recent data have shown that
      device-assisted ERCP allows for high success rates in these patients because
      various devices are useful for overcoming major difficulties. Therefore, good
      knowledge of postoperative anatomy and various devices is mandatory before
      performing ERCP procedures for post-gastrectomy patients.

PMID- 27894186
TI  - What Is the Mean Procedure Time to Optimize Colonoscopy?

PMID- 27894188
TI  - Challenges of Endoscopic Management of Pancreaticobiliary Complications in
      Surgically Altered Gastrointestinal Anatomy.
AB  - Pancreaticobiliary complications following various surgical procedures, including
      liver transplantation, are not uncommon and are important causes of morbidity and
      mortality. Therapeutic endoscopy plays a substantial role in these patients and
      can help to avoid the need for reoperation. However, the endoscopic approach in
      patients with surgically altered gastrointestinal (GI) anatomy is technically
      challenging because of the difficulty in entering the enteral limb to reach the
      target orifice to manage pancreaticobiliary complications. Additional procedural
      complexity is due to the need of special devices and accessories to obtain
      successful cannulation and absence of an elevator in forward-viewing endoscopes,
      which is frequently used in this situation. Once bilioenteric anastomosis is
      reached, the technical success rates achieved in expert hands approach those of
      patients with intact GI anatomy. The success of endoscopic therapy in patients
      with surgically altered GI anatomy depends on multiple factors, including the
      expertise of the endoscopist, understanding of postoperative anatomic changes,
      and the availability of suitable scopes and accessories for endoscopic
      management. In this issue of Clinical Endoscopy, the focused review series deals
      with pancreatobiliary endoscopy in altered GI anatomy such as bilioenteric
      anastomosis and post-gastrectomy.

PMID- 27894187
TI  - Endoscopic Ultrasound-Guided Pancreatobiliary Endoscopy in Surgically Altered
      Anatomy.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) has become the mainstay of
      therapy for pancreatobiliary diseases. While ERCP is safe and highly effective in
      the general population, the procedure remains challenging or impossible in
      patients with surgically altered anatomy (SAA). Endoscopic ultrasound (EUS)
      allows transmural access to the bile or pancreatic duct (PD) prior to ductal
      drainage using ERCP-based techniques. Also known as endosonography-guided
      cholangiopancreatography (ESCP), the procedure provides multiple advantages over
      overtube-assisted enteroscopy ERCP or percutaneous or surgical approaches.
      However, the procedure should only be performed by endoscopists experienced in
      both EUS and ERCP and with the proper tools. In this review, various EUS-guided
      diagnostic and therapeutic drainage techniques in patients with SAA are examined.
      Detailed step-by-step procedural descriptions, technical tips, feasibility, and
      safety data are also discussed.

PMID- 27894189
TI  - Ziprasidone induces cytotoxicity and genotoxicity in human peripheral
      lymphocytes.
AB  - It has been stated that some antipsychotic drugs might cause genotoxic and
      carcinogenic effects. Ziprasidone (ZIP) is commonly used an antipsychotic drug.
      However, its genotoxicity and carcinogenicity data are very limited. The
      cytotoxicity and genotoxicity of ZIP on human peripheral blood lymphocytes were
      examined in vitro by sister chromatid exchange (SCE), chromosome aberration (CA)
      and micronucleus (MN) tests in this study. Lymphocyte cultures were treated with
      50, 75 and 100 MUg/ml of ZIP in the presence and absence of a metabolic activator
      (S9 mix). Dimethylsulfoxide was used as a solvent control. While the cells were
      treated with ZIP for 24 h and 48 h in cultures without S9 mix, the cultures with
      S9 mix were exposed to ZIP for 3 h. ZIP and its metabolites can exert cytotoxic
      activities due to significant decreases in mitotic index, proliferation index and
      nuclear division index in the presence and absence of S9 mix. Statistically
      significant increases in CAs, aberrant cells and MN values in the presence and
      absence of S9 mix were found in cultures treated with ZIP. While ZIP
      significantly increased the SCE values in the absence of S9 mix at all
      concentrations, increased SCE values in cultures with S9 mix were not found to
      significantly at all concentrations tested. Our results indicated that both ZIP
      and its metabolites have cytotoxic, cytostatic and genotoxic potential on
      lymphocyte cultures under the experimental conditions. Further studies are
      necessary to make a possible risk assessment in patients receiving therapy with
      this drug.

PMID- 27894190
TI  - Adherence to combination antiretroviral treatment and clinical outcomes in a
      Medicaid sample of older HIV-infected adults.
AB  - The adherence threshold for combination antiretroviral therapy (cART) has
      historically been set at 95% or greater. We examined whether different levels of
      cART adherence (>=95% [optimal adherence], 90-94%, 80-89%, and <80%) were
      associated with different clinical outcomes (emergency department visits [ED
      visits] and duration of hospital admission) in a sample of older (50-64 years)
      persons living with HIV (PLWH). Medicaid data from 29 US states (n = 5177) were
      used for this study. cART adherence was measured and data regarding relevant
      covariates, such as race, sex, age, urbanicity, and comorbidity were obtained.
      Descriptive statistics were conducted to characterize study participants. We
      conducted univariate and multivariable regression analyses to evaluate the
      association between cART adherence and ED visits and duration of hospital
      admission while adjusting for covariates (race, sex, age, urbanicity, and
      comorbidity). Approximately 32% of all participants (n = 5177) reported optimal
      cART adherence (>=95%). After adjusting for covariates, only participants who
      reported <80% adherence were more likely to have an ED visit (adjusted odds ratio
      = 1.34, 95% CI = 1.08-1.48, p < .0001) and a longer duration of hospital
      admission (regression coefficient = 1.24, 95% CI = 0.53-1.96, p = .0007) when
      compared to participants who reported >=95% adherence. There were no significant
      differences in likelihood of having an ED visit and longer duration of hospital
      admission between participants who reported >=95% adherence and participants who
      reported 90-94% adherence and 80-89% adherence. Significant differences by
      covariates were observed. Adverse clinical outcomes were associated with low cART
      adherence (<80%) among older PLWH, though they did not differ between optimal and
      moderate cART adherence (90-94% and 80-89%). Although optimal cART adherence is
      an important goal, clinical outcomes in older PLWH may not differ between
      moderate and optimal cART adherence.

PMID- 27894191
TI  - Identifying behavioural changes in ALS: Validation of the Beaumont Behavioural
      Inventory (BBI).
AB  - OBJECTIVE: Behavioural changes are an important part of amyotrophic lateral
      sclerosis (ALS). However, most tools do not account for the influence of motor
      impairment. Furthermore, they do not fully measure the broad range of behavioural
      changes specific to ALS. This study aimed to develop and validate an ALS specific
      behavioural inventory, the Beaumont Behavioural Inventory (BBI). METHODS: The BBI
      was validated in a cohort of ALS patients (n = 85) and 78 age-, gender-, and
      education-matched controls. The scale was validated against the Frontal Systems
      Behaviour Scale (FrSBe) and The Frontal Assessment Battery (FAB) for convergent
      validity, and against other non-behavioural measures to assess discriminant
      validity. Reliability was assessed with Cronbach's alpha. RESULTS: The instrument
      showed high internal consistency (Cronbach's alpha value =0.891). BBI scores
      highly correlated with the FrSBe and moderately with the FAB. However, the
      measure was independent from non-behavioural measures. Using a cut-off score of 7
      for mild behavioural changes, the BBI displayed high sensitivity and specificity
      (87.9% and 78.85%, respectively). The cut-off score for moderate changes,
      consistent with a diagnosis of ALS-FTD, is set at 22.5, showing 90% sensitivity
      and 96% specificity. DISCUSSION: The BBI is a sensitive and specific tool to
      assess the entire behavioural spectrum of ALS.

PMID- 27894192
TI  - ALSUntangled 38: L-serine.

PMID- 27894193
TI  - Currently used and investigational drugs for Cushing's disease.
AB  - INTRODUCTION: Cushing's disease (CD) is caused by a corticotroph adenoma of the
      pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing
      increased morbidity and mortality. Surgery is the treatment of choice, but is not
      always successful. Alternatives include radiotherapy, adrenal surgery, and
      pharmaceutical therapy. The latter is increasingly gaining momentum due to the
      recent development of compounds that reduce hypercortisolaemia or its symptoms,
      acting through different mechanisms. Areas covered: In this article, the authors
      provide a complete overview of the treatment options for Cushing's disease,
      including adrenal-directed, tumor-targeted, and peripheral therapies that are
      currently used or in development, and discuss their potential advantages and
      limitations. Expert opinion: Considering the lack of long-term remission in up to
      half of the patients after surgery, and the delayed response to radiotherapy
      along with potential side effects, there is a strong need for an effective
      pharmaceutical treatment. Pasireotide, mifepristone, ketoconazole and metyrapone
      have been approved by regulatory authorities but their use remains limited due to
      considerable costs and side effects. Research in this field has focused recently
      on the improvement of pre-existing drugs and the development of safe new ones.
      However, few approaches aim at targeting the source of the disease, the ACTH
      secreting adenoma.

PMID- 27894194
TI  - Current status of syphilis in pregnant women in Japan.
AB  - We examined the current status of syphilis-infected pregnant Japanese women,
      according to the results of syphilis screening and confirmation tests of women
      who gave birth in Japan between October, 2015 and March, 2016. We requested 2458
      obstetrical facilities to provide information of syphilis screening tests and
      78.1% of them responded. Considering the response rate and the rate of
      implementation of confirmation tests, the number of syphilis-infected pregnant
      Japanese women was estimated to be 250 (1/4022) per year.

PMID- 27894195
TI  - Accelerated placental aging in early onset preeclampsia pregnancies identified by
      DNA methylation.
AB  - AIM: To determine whether dynamic DNA methylation changes in the human placenta
      can be used to predict gestational age. MATERIALS & METHODS: Publicly available
      placental DNA methylation data from 12 studies, together with our own dataset,
      using Illumina Infinium Human Methylation BeadChip arrays. RESULTS & CONCLUSION:
      We developed an accurate tool for predicting gestational age of placentas using
      62 CpG sites. There was a higher predicted gestational age for placentas from
      early onset preeclampsia cases, but not term preeclampsia, compared with their
      chronological age. Therefore, early onset preeclampsia is associated with
      placental aging. Gestational age acceleration prediction from DNA methylation
      array data may provide insight into the molecular mechanisms of pregnancy
      disorders.

PMID- 27894197
TI  - Temporal validation of a simplified blastocyst grading system.
AB  - We have recently established the clinical effectiveness and credibility of a
      simplified blastocyst grading system by demonstrating its prognostic potential
      and the inter- and intra-observer variability associated with it. To be
      considered clinically useful, however, the grading system also needs to be
      accurate (i.e. well calibrated with good discriminative ability). This study
      prospectively evaluates the performance of the grading system on subsequent
      patients from the same IVF unit in an attempt to temporally validate the model.
      All day 5 single embryo transfers between 1st July 2012 and 30th June 2014 were
      included in the study. The observed implantation, clinical pregnancy and live
      birth rates according to grade of embryo transferred were compared to the
      expected rates as predicted by the development data set and the statistical
      significance of any differences between the two were calculated using the Chi
      square test. A total of 435 single embryo transfers were included. For each grade
      of embryo transferred, there was generally no significant difference between the
      observed and expected frequencies of implantation, clinical pregnancy and live
      birth suggesting that the simplified blastocyst grading system is accurate and
      temporal validation has been satisfactorily demonstrated. It is now necessary to
      externally validate the grading system to prove generality before further
      dissemination.

PMID- 27894196
TI  - Development and characterization of folic acid-conjugated chitosan nanoparticles
      for targeted and controlled delivery of gemcitabinein lung cancer therapeutics.
AB  - The present study was designed to investigate the tumor-targeting potential of
      gemcitabine (GEM)-loaded surface-tailored chitosan (CS)/poly (ethylene glycol)
      nanoparticles (FA-PEG-GEM-NPs). The nanoparticles encapsulated with GEM were
      prepared, characterized, and tethered with folic acid. The developed formulations
      were characterized with respect to particle size/poly-dispersity index, shape,
      and zeta potential analysis. The in vitro study shows the sustained drug-release
      kinetics during 48 h. The present result shows remarkable cytotoxicity rendered
      by GEM when delivered through FA-PEG-GEM-NPs formulation. The microscopic
      assessment is suggestive of significant uptake of FA-PEG-GEM-NPs in comparison
      with the unmodified PEG-GEM-NPs and free drug. Finally, our results advocate for
      the sizeable compatibility, comparatively less organ toxicity, and higher anti
      tumor activity of ligand-anchored and PEGylated CS nanoparticles in vitro and
      corroborated by in vivo investigations. In conclusion, it is interpreted that
      surface-tailored nanoparticles are capable to ferry bioactives selectively and
      specifically to tumor sites with the interception of minimal side effects,
      thereby suggesting their potential application in cancer therapeutics.

PMID- 27894198
TI  - A randomized clinical trial of the efficacy of single versus double-daily dose of
      oral iron for prevention of iron deficiency anemia in women with twin gestations.
AB  - OBJECTIVE: The study aims to assess the efficacy of single versus double-daily
      oral iron dose on prevention of iron deficiency anemia in women with twin
      gestations. MATERIALS AND METHODS: A randomized controlled trial (NCT02858505)
      conducted at Woman's Health Hospital, Assiut, Egypt, between August 2015 and June
      2016 included 120 non-anemic pregnant women with twin gestations in the first
      trimester. Women were randomly assigned to either group I (27 mg elemental iron)
      or group II (54 mg elemental iron) daily starting from 12 weeks of pregnancy till
      36 weeks. The primary outcomes included the mean level of hemoglobin, hematocrit
      and serum ferritin at 36 weeks' gestation. RESULTS: Both iron doses maintained
      the mean hemoglobin and hematocrit within the normal level from 12 weeks to 36
      weeks (p = 0.378 and p = 0.244, respectively). However, the mean serum ferritin
      level was higher in group II than group I (p = 0.000) at 36 weeks' gestation.
      Moreover, women in group II reported more side effects than group I at 36 weeks'
      gestation. CONCLUSIONS: Doubling the prophylactic iron dose is comparable to
      single dose in the prevention of iron deficiency anemia among women with twin
      gestations with more side effects.

PMID- 27894199
TI  - Socio-economic risk patterns in Hodgkin lymphoma: not more, but new studies are
      warranted.

PMID- 27894200
TI  - Differences in the association between empirically derived dietary patterns and
      cancer: a meta-analysis.
AB  - Plant-based dietary patterns have been associated with decreased cancer risk. The
      aim of the present study was to perform a meta-analysis of studies comparing
      empirically derived dietary patterns in relation to cancer risk. A systematic
      search of PubMed and EMBASE electronic databases was conducted. Eligible studies
      had an observational design and evaluated the association with cancer risk
      between a posteriori derived dietary patterns. Random-effects models were applied
      to calculate relative risks (RRs) of cancer between diets. Statistical
      heterogeneity and publication bias were explored. An increased risk of cancer for
      the adoption of high-meat compared to plant-based dietary patterns was found (RR
      =1.64, 95% CI: 1.02, 2.63). Lower risk of cancer for individuals adopting a plant
      based dietary pattern over a mixed one was found (RR =0.88, 95% CI: 0.82, 0.95).
      In conclusion, plant-based dietary patterns can be considered a healthy choice
      over meat-based dietary patterns.

PMID- 27894201
TI  - Screening for cognitive dysfunction in ALS: validation of the Edinburgh Cognitive
      and Behavioural ALS Screen (ECAS) using age and education adjusted normative
      data.
AB  - BACKGROUND: Cognitive and behavioural changes are an important aspect in
      Amyotrophic Lateral Sclerosis (ALS). The Edinburgh Cognitive and Behavioural ALS
      Screen (ECAS) briefly assesses these changes in ALS. OBJECTIVE: To validate the
      ECAS against a standardised neuropsychological battery and assess its sensitivity
      and specificity using age and education adjusted cut-off scores. METHOD: 30
      incident ALS cases were assessed on both, ECAS and neuropsychological battery.
      Age and education adjusted cut-off scores were created from a sample of 82
      healthy controls. RESULTS: ECAS composite scores (Total, ALS Specific and Non
      Specific) were highly correlated with battery composite scores. High correlations
      were also observed between ECAS and full battery cognitive domains and subtests.
      The ECAS Total, ALS Specific and Non-Specific scores were highly sensitive to
      cognitive impairment. ECAS ALS-Specific cognitive domains also evidenced high
      sensitivity. Individual subtest sensitivity was medium to low, suggesting that
      caution should be used when interpreting these scores. Low positive predictive
      values indicated the presence of false positives. CONCLUSIONS: Psychometric
      properties of the ECAS using age and education adjusted norms indicate that the
      ECAS, when used as an overall measure of cognitive decline, is highly sensitive.
      Further comprehensive assessment is required for patients that present as
      impaired on the ECAS.

PMID- 27894202
TI  - Rolapitant for the prevention of delayed nausea and vomiting over initial and
      repeat courses of emetogenic chemotherapy.
AB  - INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a debilitating
      side effect of many cytotoxic chemotherapy regimens. Although sustained
      antiemetic control across repeated chemotherapy cycles is important for cancer
      treatment continuation, few studies have investigated the efficacy of antiemetic
      prophylaxis over multiple chemotherapy cycles. Areas covered: Here we discuss the
      use of antiemetic hydroxytryptamine type 3 (5-HT3) receptor and neurokinin (NK)-1
      receptor antagonists for prevention of CINV, limiting our review to clinical
      trials in the context of multiple-cycle chemotherapy, with a focus on the NK-1
      receptor antagonist rolapitant. 5-HT3 receptor antagonists may be effective in
      controlling CINV over repeated chemotherapy cycles, but evidence comes primarily
      from noncomparative studies. NK-1 receptor antagonists provide increased
      protection against CINV but differences in endpoint selection and methods of
      analysis preclude meaningful comparisons between agents. Rolapitant shows
      sustained control of emesis and nausea over multiple cycles of chemotherapy, and
      compared to other NK-1 receptor antagonists, has a longer half-life and reduced
      potential for cytochrome P450 3A4-mediated drug-drug interactions. Expert
      commentary: Trial design should be a key consideration in future studies of CINV
      therapies, including analytical methods utilized, choice of endpoints, and
      methods for accounting for nonresponders and patient attrition over multiple
      cycles of chemotherapy.

PMID- 27894203
TI  - Management of adverse events induced by next-generation immunomodulatory drug and
      proteasome inhibitors in multiple myeloma.
AB  - INTRODUCTION: In the last decade the introduction of novel agents has strongly
      improved multiple myeloma prognosis by doubling median overall survival.
      Unfortunately disease relapse is very common and patients may become refractory
      to previous drugs. Therefore, new therapeutic strategies are urgently needed.
      Areas covered: We have reviewed the available data on next generation novel
      agents, particularly immunomodulatory drug pomalidomide and proteasome inhibitors
      carfilzomib and ixazomib, the latter being the first-in-class orally available.
      We focused on adverse events associated with such agents and described how they
      should be managed. The main grade >=3 adverse events correlated with these drugs
      are hematologic, myelosuppression-related and reversible; non-hematologic grade
      >=3 toxicities are less frequent, with an incidence of <10%. Expert commentary:
      These agents showed to have a good tolerability. The great majority of adverse
      events are easily manageable with dose-adjustment and appropriate treatment, and
      drug discontinuation is not frequent. Favorable safety profile and high efficacy,
      especially in combination, confer to these drugs a central role in development of
      new lines of therapy against multiple myeloma. Further investigation is certainly
      needed to determine the best combinations including these agents.

PMID- 27894204
TI  - Clinical laboratory assessments for Mycoplasma genitalium in a high-prevalence
      sexually-transmitted infection community reveal epidemiologic dichotomies with
      Trichomonas vaginalis.
AB  - INTRODUCTION: Mycoplasma genitalium is an emerging agent of sexually-transmitted
      infection and is responsible for clinically-significant genital tract disease in
      both females and males. Similar to scenarios recently experienced with the
      urogenital flagellate Trichomonas vaginalis, an evolving molecular diagnostic
      reference standard based on transcription-mediated amplification allows for
      accurate detection of the organism, plus additional insight into disease
      epidemiology. Areas covered. The basis for this article includes primary peer
      reviewed literature plus compilations of data derived from routine clinical
      laboratory screening of females and males for agents of sexually-transmitted
      infection. Introductory laboratory and epidemiologic data related to T. vaginalis
      provides not only a foreshadowing to the dichotomies inherent to M. genitalium
      prevalence but also advocacy of a common non-invasive specimen source that could
      be used to screen females for both agents. This review also documents increased
      prevalence rates of M. genitalium in both females and males by way of
      transcription-mediated amplification. Expert commentary. Molecular detection of
      M. genitalium should be a consideration in the development of comprehensive
      sexually-transmitted infection screening programs for both females and males.
      Transcription-mediated amplification has additionally identified novel facets of
      M. genitalium and T. vaginalis epidemiology that warrant further investigation.

PMID- 27894205
TI  - Outcomes of second-line treatment in chronic lymphocytic leukemia - a population
      based study from a well defined geographical region between 2003 and 2013.

PMID- 27894206
TI  - Occupational exposure limits for manufactured nanomaterials, a systematic review.
AB  - BACKGROUND: The toxicological properties of manufactured nanomaterials (MNMs) can
      be different from their bulk-material and uncertainty remains about the adverse
      health effects they may have on humans. Proposals for OELs have been put forward
      which can be useful for risk management and workers' protection. We performed a
      systematic review of proposals for OELs for MNMs to better understand the extent
      of such proposals, as well as their derivation methods. METHODS: We searched
      PubMed and Embase with an extensive search string and also assessed the
      references in the included studies. Two authors extracted the data independently.
      RESULTS: We identified 20 studies that proposed in total 56 OEL values. Of these,
      two proposed a generic level for all MNMs, 14 proposed a generic OEL for a
      category of MNMs and 40 proposed an OEL for a specific nanomaterial. For specific
      fibers, four studies proposed a similar value but for carbon nanotubes (CNTs) the
      values differed with a factor ranging from 30 to 50 and for metals with a factor
      from 100 to 300. The studies did not provide explanations for this variation. We
      found that exposure to MNMs measured at selected workplaces may exceed even the
      highest proposed OEL. This indicates that the application and use of OELs may be
      useful for exposure reduction. CONCLUSION: OELs can provide a valuable reference
      point for exposure reduction measures in workplaces. There is a need for more and
      better supported OELs based on a more systematic approach to OEL derivation.

PMID- 27894207
TI  - When to recommend a second autograft in patients with relapsed myeloma?
AB  - In the current evolving landscape of myeloma therapies, no recommended salvage
      strategy exists for patients with relapsed multiple myeloma (MM) after initial
      successful autologous stem cell transplantation (ASCT) and therapeutic options
      extend from conventional chemotherapy and novel agents to second autologous and
      allogeneic transplants. In this article, we summarize the documented evidence
      about the utilization of second ASCT in patients with relapsed MM after a primary
      auto-graft and discuss the correct timing for such a salvage approach, the
      individual characteristics of patients who will benefit more, as well as the
      therapeutic role of second ASCT in the modern era of forthcoming anti-myeloma
      treatments.

PMID- 27894209
TI  - The prevalence and risk indicators of symptoms of common mental disorders among
      current and former Dutch elite athletes.
AB  - The aim of the study was to determine the prevalence and comorbidity of symptoms
      of common mental disorders (distress, anxiety/depression, sleep disturbance,
      eating disorders, adverse alcohol use) among current and former Dutch elite
      athletes, and to explore the inference between potential risk indicators (severe
      injury, surgery, life events, sport career dissatisfaction, social support) and
      the outcomes measures under investigation. Cross-sectional analyses were
      conducted on baseline questionnaires from an ongoing prospective cohort study
      among 203 current and 282 former elite Dutch athletes (response rate: 28% among
      current athletes and 95% among former athletes). Based on validated scales, an
      electronic questionnaire was set up and distributed. Prevalence (4-week) ranged
      from 6% for adverse alcohol use to 45% for anxiety/depression among current elite
      athletes, and from 18% for distress to 29% for anxiety/depression among former
      elite athletes. A higher number of past severe injuries, higher number of past
      surgeries, higher number of recent life events, higher level of career
      dissatisfaction and lower level of social support were related to the occurrence
      of symptoms of common mental disorders among both current and former elite
      athletes. On average, the 4-week prevalence of common mental disorders as shown
      in our study among current and former Dutch elite athletes were similar to the
      ones found among athletes from other sports disciplines and does compare with the
      lifetime prevalence estimates in the general population of the Netherlands.

PMID- 27894208
TI  - Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the
      detection of neuroendocrine tumors.
AB  - AIM: We wanted to explore if whole-body magnetic resonance imaging (MRI)
      including diffusion-weighted (DW) and liver-specific contrast agent-enhanced
      imaging could be valuable in lesion detection of neuroendocrine tumors (NET).
      [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP
      PET/CT) was used for comparison. MATERIALS AND METHODS: Twenty-one patients with
      NET were investigated with whole-body MRI, including DW imaging (DWI) and
      contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven
      additional patients underwent upper abdomen MRI including DWI, liver-specific
      contrast agent-enhanced imaging, and 5-HTP PET/CT. RESULTS: There was a patient
      based concordance of 61% and a lesion-based concordance of 53% between the
      modalities. MRI showed good concordance with PET in detecting bone metastases but
      was less sensitive in detecting metastases in mediastinal lymph nodes. MRI
      detected more liver metastases than 5-HTP PET/CT. CONCLUSION: Whole-body MRI with
      DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our
      findings indicate that MRI of the liver including liver-specific contrast agent
      enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT.

PMID- 27894210
TI  - Protective effects of lemongrass essential oil against benzo(a)pyrene-induced
      oxidative stress and DNA damage in human embryonic lung fibroblast cells.
AB  - Benzo(a)pyrene (BaP) was a well-known environmental pollutant, numerous studies
      had implicated BaP as a causative agent in human cancer, particularly lung
      cancer. The lemongrass essential oil (LEO) possessed various pharmacological
      activities, especially the anti-oxidative stress and cancer prevention. In the
      current study, human embryonic lung fibroblast (HELF) cells were treated with 25
      mM BaP in the absence or presence of 0.5%, 1% or 2.5% LEO and the cell viability
      and levels of oxidative stress (OS) and DNA damage in the cells were then
      measured. Nineteen chemical constituents were identified in LEO, with citral
      being the main component, representing about 68.78%. LEO was able to protect the
      HELF cells against BaP-induced loss in cell viability, achieving a maximum of
      95.58% cell viability at the 0.5% concentration. Treatment of HELF cells with BaP
      alone significantly increased the level of Malondialdehyde (MDA) and decreased
      superoxide dismutase (SOD) and catalase (CAT). However, these effects were
      suppressed when the cells were also treated with LEO, leading to enhanced levels
      of SOD and CAT activities (2.9- and 2-fold, respectively, compared with BaP
      treatment only) and reduced the level of MDA in the cells (43% reduction in
      malondialdehyde level). At the same time, LEO also reduced the level of DNA
      damage, as shown by a reduced level of 8-hydroxy-deoxyguanosine (8-OHdG). Taken
      together, the results showed that LEO offered protection against BaP-induced OS
      and DNA damage, suggesting that LEO could be a promising agent for lung cancer
      chemoprevention.

PMID- 27894212
TI  - Human instrumental performance in ratio and interval contingencies: A challenge
      for associative theory.
AB  - Associative learning theories regard the probability of reinforcement as the
      critical factor determining responding. However, the role of this factor in
      instrumental conditioning is not completely clear. In fact, free-operant
      experiments show that participants respond at a higher rate on variable ratio
      than on variable interval schedules even though the reinforcement probability is
      matched between the schedules. This difference has been attributed to the
      differential reinforcement of long inter-response times (IRTs) by interval
      schedules, which acts to slow responding. In the present study, we used a novel
      experimental design to investigate human responding under random ratio (RR) and
      regulated probability interval (RPI) schedules, a type of interval schedule that
      sets a reinforcement probability independently of the IRT duration. Participants
      responded on each type of schedule before a final choice test in which they
      distributed responding between two schedules similar to those experienced during
      training. Although response rates did not differ during training, the
      participants responded at a lower rate on the RPI schedule than on the matched RR
      schedule during the choice test. This preference cannot be attributed to a higher
      probability of reinforcement for long IRTs and questions the idea that similar
      associative processes underlie classical and instrumental conditioning.

PMID- 27894211
TI  - Parenting in infancy and self-regulation in preschool: an investigation of the
      role of attachment history.
AB  - Parenting and attachment are critical in the emergence of self-regulation (SR) in
      preschool. However, most studies use general indexes of parenting quality,
      failing to explore the unique contributions of sensitivity and home quality to
      SR. Further, the nature of the interplay between parenting and attachment history
      is not well understood. Using a sample of 938 children from The National
      Institute of Child Health and Human Development Study of Early Child Care and
      Youth Development, a series of structural equation models were fit to determine
      whether sensitivity and home quality concurrently predicted SR at 54 months, and
      whether attachment mediated or moderated these pathways. Results suggest that
      both sensitivity and home quality uniquely predict SR. Further, these early
      parenting variables were each indirectly associated with SR through children's
      attachment history. That is, higher levels of sensitivity and home quality
      predicted secure attachment history, which, along with parenting, predicted more
      advanced SR skills at 54 months. No moderated pathways emerged, suggesting that
      attachment history may be best conceptualized as a mediating mechanism.

PMID- 27894213
TI  - Factor solutions of the Social Phobia Scale (SPS) and the Social Interaction
      Anxiety Scale (SIAS) in a Swedish population.
AB  - Culturally validated rating scales for social anxiety disorder (SAD) are of
      significant importance when screening for the disorder, as well as for evaluating
      treatment efficacy. This study examined construct validity and additional
      psychometric properties of two commonly used scales, the Social Phobia Scale and
      the Social Interaction Anxiety Scale, in a clinical SAD population (n = 180) and
      in a normal population (n = 614) in Sweden. Confirmatory factor analyses of
      previously reported factor solutions were tested but did not reveal acceptable
      fit. Exploratory factor analyses (EFA) of the joint structure of the scales in
      the total population yielded a two-factor model (performance anxiety and social
      interaction anxiety), whereas EFA in the clinical sample revealed a three-factor
      solution, a social interaction anxiety factor and two performance anxiety
      factors. The SPS and SIAS showed good to excellent internal consistency, and
      discriminated well between patients with SAD and a normal population sample. Both
      scales showed good convergent validity with an established measure of SAD,
      whereas the discriminant validity of symptoms of social anxiety and depression
      could not be confirmed. The optimal cut-off score for SPS and SIAS were 18 and 22
      points, respectively. It is concluded that the factor structure and the
      additional psychometric properties of SPS and SIAS support the use of the scales
      for assessment in a Swedish population.

PMID- 27894214
TI  - Quantitation using a stable isotope dilution assay (SIDA) and thresholds of taste
      active pyroglutamyl decapeptide ethyl esters (PGDPEs) in sake.
AB  - A stable isotope dilution assay (SIDA) for two taste-active pyroglutamyl
      decapeptide ethyl esters (PGDPE1; (pGlu)LFGPNVNPWCOOC2H5, PGDPE2;
      (pGlu)LFNPSTNPWCOOC2H5) in sake was developed using deuterated isotopes and high
      resolution mass spectrometry. Recognition thresholds of PGDPEs in sake were
      estimated as 3.8 MUg/L for PGDPE1 and 8.1 MUg/L for PGDPE2, evaluated using 11
      student panelists aged in their twenties. Quantitated concentrations in 18
      commercial sake samples ranged from 0 to 27 MUg/L for PGDPE1 and from 0 to 202
      MUg/L for PGDPE2. The maximum levels of PGDPE1 and PGDPE2 in the sake samples
      were approximately 8 and 25 times higher than the estimated recognition
      thresholds, respectively. The results indicated that PGDPEs may play significant
      sensory roles in the sake. The level of PGDPEs in unpasteurized sake samples
      decreased during storage for 50 days at 6  degrees C, suggesting PGDPEs may be
      enzymatically decomposed.

PMID- 27894215
TI  - The molecular pathogenesis of mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14) leading
      to constitutive cyclin D1 overexpression. However, overexpression of cyclin D1
      alone is insufficient to cause malignant transformation. Secondary genetic
      alterations and deregulated signaling pathways involved in DNA damage response,
      cell proliferation, and apoptosis are indispensable for MCL lymphomagenesis.
      Recent studies investigating the biology of MCL have revealed crucial importance
      of B-cell receptor (BCR), nuclear factor-kappa B (NF-kappaB), phosphoinositide 3
      kinase (PI3K), and BCL2 signaling for the molecular pathogenesis of MCL. In
      addition, activation of the Janus kinase (JAK)/signal transducer and activator of
      transcription 3 (STAT3), NOTCH and WNT pathway can be observed in subsets of
      MCLs. These addictions can potentially be utilized therapeutically by
      implementing small molecule inhibitors into current treatment regimens.

PMID- 27894216
TI  - Bone effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in
      patients with type 2 diabetes mellitus.
AB  - Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for
      the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by
      inhibiting renal glucose reabsorption and increasing urinary glucose excretion.
      It has been reported that SGLT2 inhibitors may have potential adverse effects on
      bone, including increased fracture risk and decreased bone mineral density (BMD).
      Across clinical studies, canagliflozin was not associated with meaningful changes
      in serum or urine calcium, vitamin D, or parathyroid hormone. Minimal increases
      in serum phosphate and magnesium that were within normal limits were seen with
      canagliflozin versus placebo. Canagliflozin was associated with increases in
      serum collagen type 1 beta-carboxy telopeptide (beta-CTX), a bone resorption
      marker, and osteocalcin, a bone formation marker. Decreases in total hip BMD were
      seen with canagliflozin 100 and 300 mg versus placebo after 2 years (-1.7%, 
      2.1%, -0.8%; differences of -0.9% and -1.2%), but not at other skeletal sites
      (normal age-related bone loss, ~0.5-1.0%/year). Changes in beta-CTX and total hip
      BMD were significantly associated with weight loss, which is known to increase
      bone resorption markers and decrease BMD. Canagliflozin was associated with a
      higher fracture incidence in an interim analysis of the CANagliflozin
      cardioVascular Assessment Study (CANVAS) in patients with a history or high risk
      of cardiovascular disease (incidence per 100 patient-years of 1.6, 1.6, and 1.1
      with canagliflozin 100 and 300 mg and placebo), but not in other clinical studies
      of patients with T2DM. Fractures tended to occur as early as 12 weeks after
      initiating treatment and were primarily located in the distal parts of the upper
      and lower extremities. The reason for increased fracture risk with canagliflozin
      treatment is unknown, but is likely not related to a direct effect of
      canagliflozin on bone-related biomarkers. Data from ongoing canagliflozin
      studies, including CANVAS, will provide additional information on fracture risk
      in patients with T2DM.

PMID- 27894217
TI  - Diagnosis, clinical manifestations and management of rare bleeding disorders in
      Iran.
AB  - BACKGROUND: Rare bleeding disorders (RBDs) are heterogeneous disorders, mostly
      inherited in an autosomal recessive pattern. Iran is a Mideast country with a
      high rate of consanguinity that has a high rate of RBDs. OBJECTIVE: In this
      study, we present prevalence and clinical presentation as well as management and
      genetic defects of Iranian patients with RBDs. METHODS: For this study, all
      relevant publications were searched in Medlin until 2015. RESULTS AND DISCUSSION:
      Iran has the highest global incidence of factor XIII deficiency. Factor VII
      deficiency also is common in Iran, while factor II deficiency, with a prevalence
      of 1 per ~3 million, is the rarest form of RBDs. Factor activity is available for
      all RBDs except for factor XIII deficiency, in which clot solubility remains as a
      diagnostic test. Molecular analysis of Iranian patients with RBDs revealed a few
      recurrent, common mutations only in patients with factor XIII deficiency, and
      considerable novel mutations in other RBDs. Clinical manifestations of these
      patients are variable and patients with factor XIII, factor X and factor VII more
      commonly presented severe life-threatening bleeding, while patients with combined
      factor V and factor VIII presented a milder phenotype. Plasma-derived products
      are the most common therapeutic choice in Iran, used prophylactically or on
      demand for the management of these patients. CONCLUSION: Since Iran has a high
      rate of RBDs with life-threatening bleeding, molecular studies can be used for
      carrier detection and, therefore, prevention of the further expansion of these
      disorders and their fatal consequence.

PMID- 27894218
TI  - Molecular and cellular studies on the absorption, function, and safety of food
      components in intestinal epithelial cells.
AB  - The intestinal tract comes into direct contact with the external environment
      despite being inside the body. Intestinal epithelial cells, which line the inner
      face of the intestinal tract, have various important functions, including
      absorption of food substances, immune functions such as cytokine secretion, and
      barrier function against xenobiotics by means of detoxification enzymes. It is
      likely that the functions of intestinal epithelial cells are regulated or
      modulated by these components because they are frequently exposed to food
      components at high concentrations. This review summarizes our research on the
      interaction between intestinal epithelial cells and food components at cellular
      and molecular levels. The influence of xenobiotic contamination in foods on the
      cellular function of intestinal epithelial cells is also described in this
      review.

PMID- 27894219
TI  - Exposure to culturally sensitive sexual health information and impact on health
      literacy: a qualitative study among newly arrived refugee women in Sweden.
AB  - In Sweden, migrants have poorer sexual and reproductive health compared to the
      general population. Health literacy, in the form of the cognitive and social
      skills enabling access to health promoting activities, is often poorer among
      migrants, partly due to language and cultural barriers. Culturally sensitive
      health education provides a strategy for enhancing health literacy. Since 2012,
      specially trained civic and health communicators have provided sexual and
      reproductive health and rights information to newly arrived refugees in Skane,
      Sweden. The aim of this study was to explore how information on sexual and
      reproductive health and rights was perceived by female recipients and whether
      being exposed to such information contributed to enhanced sexual and reproductive
      health and rights literacy. Semi-structured in-depth interviews were conducted
      with nine women and analysed using qualitative content analysis. Two themes
      emerged: (1) opening the doors to new understandings of sexual and reproductive
      health and rights and (2) planting the seed for engagement in sexual and
      reproductive health and rights issues, illustrating how cultural norms influenced
      perceptions, but also how information opened up opportunities for challenging
      these norms. Gender-separate groups may facilitate information uptake, while
      discussion concerning sexual health norms may benefit from taking place in mixed
      groups.

PMID- 27894220
TI  - The role of the Pharmacist in the design, development and implementation of
      Medication Prescription Support Systems.
AB  - Clinical Decision Support Systems (CDSS) are computerized tools designed to help
      healthcare professionals to make clinical and therapeutic decisions, with the
      objective of improving patient care. Prescription-targeted CDSS have the highest
      impact in improving patient safety. Although there are different designs and
      functionalities, all these systems will combine clinical knowledge and patient
      information in a smart manner, in order to improve the prescription process. With
      the emergence of new technologies and advances in smart decision systems, the
      implementation of said systems can achieve an important improvement in terms of
      the prescription process and patient safety. The design and implementation of
      these systems should be performed by a multidisciplinary team of professionals,
      where Pharmacists will play an important role due to their technical knowledge
      about medications and the technologies associated to their use. This article aims
      to provide basic guidelines for the design and adequate implementation,
      monitoring and follow-up of Clinical Decision Support Systems within the setting
      of pharmacological prescription.

PMID- 27894221
TI  - Effectiveness and safety of pemetrexed for non-small cell lung cancer in the
      Andalusian Public Health System.
AB  - OBJECTIVE: To evaluate effectiveness and safety profile of pemetrexed in patients
      with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when it's
      used on real clinical practice in Andalusia (a Spanish region with 8.5 million
      inhabitants, 2014 census data). METHODS: An observational multicentre
      retrospective study was conducted. Adult patients with locally
      advanced/metastatic NSCLC who received pemetrexed in any hospital in the
      Andalusian Public Health System during the last term of 2011 were included. We
      collected patients' baseline characteristics, diagnostic and treatment data,
      effectiveness variables (response to treatment with pemetrexed and
      overallsurvival) and main adverse reactions detected. RESULTS: 172 patients from
      17 hospitals were included (77.33% were men), median age 63 years old (between 34
      and 83). The predominant histology was adenocarcinoma (84.30%) and 85.20% were
      diagnosed of lung cancer with IV-stage. 78.49% had been smokers at some point in
      their lives. Median overall survival from the start of pemetrexed was 9 months
      (95%CI, 4.1-13.9). Progression of the disease was the most frequent response
      (33.14%), only one patient had complete response. Stable disease was associated
      with a higher probability of survival. Main adverse reactions detected were
      asthenia, haematological reactions, gastrointestinal reactions and dermal o
      mucous toxicity. No patients discontinued treatment for serious toxicity.
      CONCLUSIONS: Pemetrexed resulted quite effective in NSCLC when it was used on
      real clinical practice, with higher survival in non-squamous histology and
      patients with the best score of Eastern Cooperative Oncology Group scale. The
      toxicity profile was well tolerated. Prospective studies would be needed to
      confirm the effect of prognostic factors observed.

PMID- 27894222
TI  - [Training degree assessment of staff producing parenteral nutrition in Pharmacy
      Services].
AB  - OBJECTIVE: To assess the level of expertise of Pharmacy personnel in the
      manufacturing of total parenteral nutrition. MATERIAL AND METHODS: An on-line
      survey including 17 questions concerning key aspects of TPN manufacturing was
      designed. Survey monkey software was used to create the survey and to analize its
      results. RESULTS: 135 answers were received. 95% of the participant Pharmacy
      services had written standard manufacturing procedures. 67% answered that
      phosphate salts should be the first electrolite to be additioned into the total
      parenteral nutrition and 34% affirmed that validation of the aseptic
      manufacturing technique was not performed. As far as personnel training was
      concerned, 19% of respondents had not received any specific training, although
      99% considered it would be necessary to receive it. CONCLUSIONS: The polled
      personell has an acceptable level of expertise but adequate training courses are
      still necessary and should be promoted from Pharmacy services.

PMID- 27894223
TI  - [Oncology medications prescription in a cancer service: appropriateness to
      clinical practice guidelines].
AB  - OBJECTIVE: To assess prescription of oncology medications in municipal public
      health network of Rosario for its appropriateness to clinical practice
      guidelines. METHODS: Descriptive pharmacoepidemiological study in adult patients
      in an Oncology Service between January and June 2012. Compliance requirements
      with clinical practice guidelines were evaluated. RESULTS: 51.8% of diagnoses had
      at least one prescription medication that did not match recommendation by at
      least one of the guides considered. Prescriptions of doxorrubicine and ifosfamide
      did not agree with the recommendation of any reference guides. 5.4% of
      prescriptions weren't considered by local guides, nor 7.7% by national on es.
      Regarding comparison with international guidelines: 4.2% of prescriptions weren
      't considered by the European Society for Medical Oncology guidelines, 2.3% not
      considered by the American Cancer Society and only 1.9% were not considered by
      the National Comprehensive Cancer Network ones. CONCLUSIONS: Prescription of
      oncology treatments is closer to international reference guides. One reason could
      be that there is still no standard definition in the management of tumor diseases
      by the National State.

PMID- 27894224
TI  - Comparative study of preparation of hazardous drugs with different closed-system
      drug transfer devices by means of simulation with fluorescein.
AB  - OBJECTIVES: The level of environmental contamination generated during preparation
      and administration of hazardous drugs using different valve closed-systems and
      their combinations was compared. The actual impact on the overall time of
      preparation of cytostatics and the economic cost of the different modalities were
      also compared. METHODS: Comparative study of the preparation of fluorescein
      mixtures with different modalities of valve closed-system combinations.
      Environmental contamination was detected in critical points of connection, and in
      splashes produced at any other points. The main variable was qualitative
      detection of contamination by splashes through ultraviolet light when modalities
      with or without a connector were compared. A final number of 160 mixtures were
      prepared to detect differences of at least 5%. RESULTS: Splashes were produced in
      7 preparations without a connector (p = 0.015). No significant differences (p =
      0.445) were detected either in the use of a supporting vial spike vs an anchoring
      spike, or in the ChemoCLAVE(r) system vs valve systems with Fleboflex(r)
      solutions. Contamination at any critical point was produced in all preparations.
      The use of a supporting vial spike, syringe connector and bag solution with Luer
      connection was the most efficient modality. CONCLUSIONS: A syringe connector is
      needed to guarantee a closed system. Anchoring spikes do not show higher
      advantages as compared with supporting vial spikes. Fleboflex(r) solutions with
      Luer bags are more efficient than ChemoCLAVE(r) and show similar safety. However,
      connections of these closed systems are not leak-tight, and it is therefore
      important to continue studies of contamination of the different closed system
      transfer devices.

PMID- 27894225
TI  - Agreement between the 2009 STOPP Criteria and the 2003 Beers Criteria at the time
      of hospital admission.
AB  - : Potentially inappropriate prescription in elderly patients can be evaluated by
      different methods. The STOPP Criteria and Beers Criteria stand out among the
      explicit criteria most widely used. OBJECTIVE: The main objective of this study
      is to identify the agreement in the detection of potentially inappropriate
      prescribing between the STOPP criteria and the Beers Criteria, in elderly
      patients assessed at the time of hospital admission. METHOD: An observational
      retrospective study was designed in order to estimate the prevalence of
      potentially inappropriate prescription in the habitual treatment before
      admission, and to compare the agreement in detection capability between the 2003
      Beers Criteria and the 2009 STOPP Criteria, in >70-yearold patients with an
      emergency hospital admission. There was also a specific analysis of the
      prescription of first-generation antihistamines, tricyclic antidepressants,
      benzodiazepines, and selective serotonin reuptake inhibitors, which are
      considered drugs with irregular management and potential toxicity. RESULTS: The
      total prevalence of patients with a potentially inappropriate prescription was
      23.8% using the Beers Criteria and 33.3% using the STOPP Criteria. There was a
      low level of agreement between both questionnaires. First-generation
      antihistamines (Beers) and pharmacological duplication (STOPP J) were the
      criteria most frequently found. There were differences in the prevalence of
      potentially inappropriate prescription in the four pharmacological groups
      selected; and in all cases, detection by Beers Criteria was superior. CONCLUSION:
      There is no agreement between the STOPP Criteria and the Beers Criteria regarding
      the detection of patients with potentially inappropriate prescribing at the time
      of hospital admission.

PMID- 27894227
TI  - Multidisciplinary teams involved: detection of drug-related problems through
      continuity of care.
AB  - OBJECTIVE: To quantify Drug-Related problems (DRPs) by establishing a Strategic
      Continuity of Care Program (e-Conecta- Concilia Program; e-CC) focused on the
      drug therapy of patients within an Integrated Management Structure, in order to
      guarantee the therapeutical efficiency, safety and traceability of patients.
      METHOD: A prospective study at 8 months. The project included 22 Hospital
      Pharmacists and 12 Primary Care Pharmacists. Electronic clinical records were
      used, which can be accessed by all healthcare levels. Those interventions
      required in order to create a Standard Operating Procedure (SOP) were carried out
      (creation of working groups, computing, meeting points), for coordination among
      pharmacists in different care levels through a common communication system. The
      working groups formed by pharmacists of both care levels established the
      following inclusion criteria: patients with chronic diseases and polymedicated,
      patients for whom drug-related problems (DRP) had been detected, detection of any
      off-label use in Primary Care, or discrepancies in the standardization of medical
      prescriptions. RESULTS: In the setting of the e-CC program, interventions were
      unified and discrepancies were identified. During this project, 245 drug-related
      problems were detected; the majority regarding inadequate dosing, regimen, or
      duration (24%), and involving Group B medications (33%), according to the ATC
      classification. CONCLUSIONS: The implementation of a Continuity of Care SOP
      between pharmacists allowed to detect and solve DRPs and discrepancies in patient
      pharmacotherapy, with a high rate of acceptance (84.1%) of interventions.

PMID- 27894226
TI  - Adaptation of oral medication in people institutionalized in nursing homes for
      whom medication is crushed: The ADECUA Study.
AB  - PURPOSE: To evaluate the effect of pharmacist interventions in the adaptation of
      pharmaceutical forms in elders institutionalized in nursing homes whose medicines
      are crushed, which may have a clinical relevance. METHODS: Quasi-experimental,
      multicenter, transversal and prospective study carried out in 10 nursing homes.
      Subjects for whom drugs were being crushed were identified. Their treatments were
      reviewed in order to identify drugs that should not be crushed. In these cases,
      we proposed an alternative to the physician and we evaluated the degree of
      acceptance, its association to other variables and the pre-post adaptation index
      (tablets that can be crushed and capsules that can be opened/ total number of
      tablets and capsules before and after the intervention). Moreover, health
      professionals received a training course. RESULTS: Medication was being crushed
      for 33% (618/1875) of residents (mean: 5 drugs susceptible of crushing). 220
      pharmaceutical interventions were performed, mostly in extended release or gastro
      resistant drugs (48% were accepted). Switch was the type of intervention more
      frequent (79%), mainly to Purpose: To evaluate the effect of pharmacist
      interventions in the adaptation of pharmaceutical forms in elders
      institutionalized in nursing homes whose medicines are crushed, which may have a
      clinical relevance. METHODS: Quasi-experimental, multicenter, transversal and
      prospective study carried out in 10 nursing homes. Subjects for whom drugs were
      being crushed were identified. Their treatments were reviewed in order to
      identify drugs that should not be crushed. In these cases, we proposed an
      alternative to the physician and we evaluated the degree of acceptance, its
      association to other variables and the pre-post adaptation index (tablets that
      can be crushed and capsules that can be opened/ total number of tablets and
      capsules before and after the intervention). Moreover, health professionals
      received a training course. RESULTS: Medication was being crushed for 33%
      (618/1875) of residents (mean: 5 drugs susceptible of crushing). 220
      pharmaceutical interventions were performed, mostly in extended release or gastro
      resistant drugs (48% were accepted). Switch was the type of intervention more
      frequent (79%), mainly to.

PMID- 27894228
TI  - Development of a taxonomy for pharmaceutical interventions in HIV+ patients based
      on the CMO model.
AB  - OBJECTIVE: To agree on a proposal for pharmaceutical interventions and establish
      their classification taxonomy according to the CMO-Pharmaceutical Care Model
      (Capacity-Motivation- Opportunity). METHOD: A study conducted between March and
      May, 2016. Two phases of development were defined. A literature review was
      initially conducted. Then, the DELPHI-Rand-UCLA methodology was used in order to
      reach a consensus about those interventions selected, and to define the taxonomy.
      Fifteen (15) experts, specialists in Pharmaceutical Care for HIV+ patients, were
      selected. This selection was explicitly conducted, following a protocol in order
      to avoid any bias. An initial proposal was developed according to the
      interventions extracted from Phase 1. These were tentatively classified according
      to the CMO Model, in a category based on their design and utility. Three issues
      were raised from the initial question: Do you agree with the proposed
      classification? If not, there was an option to re-categorize. Additionally, they
      were asked about the importance, priority and impact to achieve
      pharmacotherapeutic objectives that they would assign to it. Interventions were
      classified according to the degree of agreement. Once a consensus was reached,
      the final taxonomy was established. RESULTS: Eighteen (18) articles were finally
      considered. The initial proposal included 20 pharmaceutical interventions with
      the following classification: seven in Capacity, eight in Motivation, and five in
      Opportunity. Those interventions considered to have greater importance and
      priority were: Review and Validation, Safety, and Adherence. The interventions
      with the greatest impact were: Review and Validation, Coordination, Adherence,
      and Motivation. On the other hand, the lowest scores for importance were for:
      Planning and Social Coordination; and in terms of impact: Social Coordination.
      CONCLUSIONS: The taxonomy reached by consensus will allow to classify
      pharmaceutical interventions with the new model, and therefore to conduct an
      improved research and patient care.

PMID- 27894229
TI  - [Self-reported experience in patients treated with Hepatitis C direct acting
      antivirals].
AB  - BACKGROUND AND OBJECTIVE: To learn about and analyze the self-reported treatment
      experience of HCV patients who started treatment with direct acting antivirals
      agents (DAA), at a real-time, proactive and integrated into the pharmaceutical
      care healthcare process, using a prospective questionnaire completed by patients
      as clinical tool. MATERIAL AND METHODS: Observational and cross-sectional study
      conducted between April (start of the National Strategic Plan) and December 2015
      in the Outpatient Pharmacy Service. The questionnaire includes variables related
      to health related quality of life (HRQOL), adherence, adverse effects (AEs),
      satisfaction, and usefulness of the Pharmacy Service implemented training
      program. A descriptive analysis of all variables included in the study was
      conducted and the influence of different variables analyzed in the degree of
      adherence and HRQOL. The analysis of the differences was performed using chi
      square test and simple logistic regression model for calculation of OR. We use
      SPSS version 20 program and statistical significance for values of p < 0.05 was
      considered. RESULTS: 155 of the 226 surveys returned, with a response rate of
      68.6%. Referring to the HRQOL (evaluation of physical and emotional state), 38.7%
      of patients reports that their physical and emotional state is much better from
      the start of treatment. The presence of EA and worse global information of their
      disease was associated with worse physical and emotional state (p < 0.05).
      Reported adherence was 84.5% and the treatment was evaluated as very good or good
      by 87% of patients. 52.9% had no adverse effects related to the medication and
      the training process performed by the specialist pharmacist at the first visit
      96.7% of patients assessed as very good or good. CONCLUSIONS: Self-reported
      experience acquired through direct and constant contact with patients provides
      information on important aspects of treatment. We believe that these tools should
      be incorporated into pharmaceutical care procedures as a way to maintain
      continuity in patients direct contact. They also induce patients to a self
      assessment of various aspects of their own treatment, which can help achieve
      greater involvement in it and can contribute to achieve the maximum health
      outcome in pharmacotherapy.

PMID- 27894230
TI  - Factor VIII delivery devices in haemophilia A. Barriers and drivers for treatment
      adherence.
AB  - INTRODUCTION AND OBJECTIVE: To capture the experience of haemophilia A patients
      with their devices for coagulation factor reconstitution, the barriers for
      treatment adherence; and to determine their preferences, presenting a new double
      chamber syringe (DCS). METHOD: A cross-sectional research through a supervised
      survey and a DCS testing session. RESULTS: Seventy-four (74) patients
      participated, 50% of them on prophylaxis treatment, and 7 years (median) with
      their usual treatment (IQR 17.25). In the survey, the DCS received the highest
      score (75/100, p < 0.001) and it was the most likely to be used in prophylactic
      treatment (p < 0.001). In the practical testing session (n = 29), 62.1% preferred
      the DCS, and required 43 seconds as median time (24.5-82) for preparation, vs. 4
      minutes (1-15) with their usual treatment (p < 0.001). The favourable opinion of
      their doctor regarding prophylaxis was very influential on the attitude of
      participants towards treatment adherence (OR = 1.324, CI 95% = 1.040-1.685, p =
      0.023). CONCLUSIONS: The DCS was the preferred device, and was likely to
      encourage prophylaxis.

PMID- 27894231
TI  - Evidence of exposure to cytostatic drugs in healthcare staff: a review of recent
      literature.
AB  - OBJECTIVE: Provide updated evidence and learn about the actions that must be
      implemented in order to prevent the occupational exposure to cytostatic drugs.
      METHOD: A bibliographic search was carried out on the MEDLINE, COCHRANE PLUS and
      WEB OF SCIENCE databases, with the terms "surface contamination", "cytostatic
      drug", "drug preparation", "occupational exposure", "safe handling" and "closed
      system transfer device", within the 2010-2015 period. RESULTS: Thirteen articles
      were selected for review. These articles are from hospitals in U.S.A., Canada,
      Japan, Australia, Spain, Portugal and Germany. In all of them, surface
      contamination by cytostatic agents was found in over 15 different surfaces, with
      concentrations ranging from 1.69 ng/cm2 to 4-784 MUg/cm2. The specific drugs were
      cyclophosphamide, ifosfamide, 5-fluorouracil, methotrexate, paclitaxel,
      cisplatin, gemcitabine, and docetaxel. Closed-system transfer devices can reduce
      the contamination in work surfaces significantly, but do not eliminate it.
      CONCLUSIONS: Presence of contamination by cytostatic drugs was confirmed in many
      hospitals across all 5 continents. In all cases, contamination was found in the
      cabinet, on the floor in front of the cabinet, and in other places of the
      Hospital Pharmacy. The drug most frequently found was cyclophosphamide. The most
      effective action used to reduce contamination was the closed-system transfer
      devices (CSTDs).

PMID- 27894232
TI  - [Myoclonus associated with Ciprofloxacin therapy].

PMID- 27894233
TI  - [Lung infiltrates associated with sertraline administration].

PMID- 27894234
TI  - [Annual Index].

PMID- 27894235
TI  - Energy Efficient Graphene Based High Performance Capacitors.
AB  - BACKGROUND: Graphene (GRP) is an interesting class of nano-structured electronic
      materials for various cutting-edge applications. OBJECTIVE: To date, extensive
      research activities have been performed on the investigation of diverse
      properties of GRP. The incorporation of this elegant material can be very
      lucrative in terms of practical applications in energy storage/conversion
      systems. METHOD: Among various those systems, high performance electrochemical
      capacitors (ECs) have become popular due to the recent need for energy efficient
      and portable devices. Therefore, in this article, the application of GRP for
      capacitors is described succinctly. In particular, a concise summary on the
      previous research activities regarding GRP based capacitors is also covered
      extensively. RESULT: It was revealed that a lot of secondary materials such as
      polymers and metal oxides have been introduced to improve the performance. Also,
      diverse devices have been combined with capacitors for better use. CONCLUSION:
      More importantly, recent patents related to the preparation and application of
      GRP based capacitors are also introduced briefly. This article can provide
      essential information for future study.

PMID- 27894237
TI  - New Insight in Improving Therapeutic Efficacy of Antipsychotic Agents: An
      Overview of Improved In Vitro and In Vivo Performance, Efficacy Upgradation and
      Future Prospects.
AB  - Psychotic disorders are recognized as severe mental disorders that rigorously
      affect patient's personality, critical thinking, and perceptional ability. High
      prevalence, global dissemination and limitations of conventional pharmacological
      approaches compel a significant burden to the patient, medical professionals and
      the healthcare system. To date, numerous orally administered therapies are
      available for the management of depressive disorders, schizophrenia, anxiety,
      bipolar disorders and autism spectrum problems. However, poor water solubility,
      erratic oral absorption, extensive first-pass metabolism, low oral
      bioavailability and short half-lives are the major factors which limit the
      pharmaceutical significance and therapeutic feasibility of these agents. In
      recent decades, nanotechnology-based delivery systems have gained remarkable
      attention of the researchers to mitigate the pharmaceutical issues related to the
      antipsychotic therapies and to optimize their oral drug delivery, therapeutic
      outcomes, and patient compliance. Therefore, the present review was aimed to
      summarize the available in vitro and in vivo evidences signifying the
      pharmaceutical importance of the advanced delivery systems in improving the
      aqueous solubility, transmembrane permeability, oral bioavailability and
      therapeutic outcome of the antipsychotic agents.

PMID- 27894238
TI  - Anatomical Approach to Clinical Problems of Popliteal Fossa.
AB  - BACKGROUND: Popliteal fossa, also known as the popliteal space, is located behind
      the knee joint. This region can develop many clinical complications in the
      vascular, nervous, lymphatics, adipose, as well as swelling and masses.
      OBJECTIVE: The objective of this review article is to give a detailed
      understanding of the popliteal fossa and the clinical pathology that may present
      itself. METHODS: MEDLINE(r) searches were conducted of literature published since
      1950s for "popliteal fossa," "diseases," "anatomy," "arterial," "venous,"
      "nerves," "entrapment syndrome," "aneurysms," "cysts," "lymphatics," "solid
      masses," "tumors," "inflammatory lesions," and "swellings." The references
      provide up-to-date literature for all the pathologies discussed. RESULTS: This
      review articles discusses the anatomy, clinical examination, including history,
      physical, and imaging modalities, and various diseases that present themselves in
      patients. Diseases relating to the arterial and venous systems, nervous system,
      musculature, adipose, lymphatics, cysts and other solid masses, including
      neoplasms, and abscesses. The differential diagnosis and symptoms of certain
      conditions are addressed to isolate the root of the manifestation. CONCLUSION:
      Diseases of the popliteal fossa can use histology and electrophysiology to aid in
      diagnosis, as well as instrumentation. Surgical approaches are uses to treat
      varying pathologies as they are the best means of therapy.

PMID- 27894239
TI  - Do Biologic Agents Increase the Risk of Infection in Patients Undergoing Lower
      Limb Arthroplasty Surgery?
AB  - BACKGROUND: Biologic agents have contributed significantly to the management of
      patients with in rheumatoid arthritis (RA). A significant proportion of patients
      with RA still require arthroplasty procedures however. It is unclear whether
      these agents increase the risk of post operative infection after lower limb
      arthroplasty. METHOD: A literature search was performed for articles published
      over the last 10 years in the English language examining the association between
      anti-tumour necrosis factor inhibitors and the incidence of post operative
      infection in patients with RA undergoing hip and knee arthroplasty procedures.
      RESULTS: One large meta-analysis has been published suggesting a 2-fold increase
      in infection rates following orthopaedic surgery in patients receiving biological
      agents. When subgroup analysis of arthroplasty cases alone was performed the
      finding failed to reach significance. However, several further studies have
      demonstrated both an increased risk for surgical site infection with the use of
      biological agents and several conflicting articles argue the opposite.
      CONCLUSION: There is no current consensus on this topic. The safety of
      continuation of perioperative anti-TNF-alpha therapy in patients undergoing lower
      limb arthroplasty procedures is unclear. There is also little robust guidance
      from specialist rheumatologic societies. There is need for large scale
      multicentre randomised controlled trials to address this issue.

PMID- 27894240
TI  - SUMOylation Regulation of Retina Development and Functions.
AB  - The structure and developmental mechanisms of vertebrate retina are highly
      conserved. One of the most distinctive events during retinogenesis is the
      temporally and spatially generation of seven types of retinal cells from the
      multipotent retinal progenitor cells. The importance and prevalence of
      SUMOylation in regulation of this process through modulation of gene expression
      and protein function diversity have been increasingly appreciated. Here, we
      review the biological significance of SUMOylation in retina development, examine
      how SUMOylation balances the proliferation and cell cycle exit of retinal
      progenitor cells, and finally discuss the molecular mechanisms mediating the
      specification of different retina neurons and photoreceptors through modulation
      of various transcription factors. The potential role of SUMOylation in normal
      retina function is illustrated by the abundant expression of key components of
      SUMOylation machinery in mouse retina, and is also exemplified by the highly
      conserved SUMOylation site on neurotransmission receptors in ganglion cells.

PMID- 27894241
TI  - A Novel Relationship for Schizophrenia, Bipolar and Major Depressive Disorder
      Part 6: A Hint from Chromosome 6 High Density Association Screen.
AB  - BACKGROUND: Convergent evidence from genetics, symptomatology and
      psychopharmacology imply that there are intrinsic connections between
      schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD),
      for example, any two or even three of these disorders could co-exist in some
      families. OBJECTIVE: To screen out the susceptibility genes on chromosome 6
      comprehensively for SCZ, BPD and MDD in a relative homogenous population in
      China. METHOD: A total of 56.400 single nucleotide polymorphism (SNPs) on
      chromosome 6 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119
      SCZ, 253 BPD (type- I), 177 MDD patients and 1000 controls. RESULTS: Associated
      SNP loci on chromosome 6 were comprehensively revealed and outstanding
      susceptibility genes were identified including JARID2 (Homo sapiens jumonji, AT
      rich interactive domain 2) which plays an essential role in embryonic development
      and neural tube fusion process. Unexpectedly, flanking genes for all associated
      SNPs were replicated in an enlarged cohort of 986 SCZ patients. CONCLUSION:
      Considering all evidence, our results imply that both of bipolar disorder and
      major depressive disorder are subtypes of schizophrenia. Furthermore, JARID2 is
      an important psychosis gene in this population.

PMID- 27894236
TI  - Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for
      Vaccine and Therapeutics.
AB  - BACKGROUND: Staphylococcus aureus is a major bacterial pathogen capable of
      causing a range of infections in humans from gastrointestinal disease, skin and
      soft tissue infections, to severe outcomes such as sepsis. Staphylococcal
      infections in humans can be frequent and recurring, with treatments becoming less
      effective due to the growing persistence of antibiotic resistant S. aureus
      strains. Due to the prevalence of antibiotic resistance, and the current
      limitations on antibiotic development, an active and highly promising avenue of
      research has been to develop strategies to specifically inhibit the activity of
      virulence factors produced S. aureus as an alternative means to treat disease.
      OBJECTIVE: In this review we specifically highlight several major virulence
      factors produced by S. aureus for which recent advances in antivirulence
      approaches may hold promise as an alternative means to treating diseases caused
      by this pathogen. Strategies to inhibit virulence factors can range from small
      molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence
      proteins. CONCLUSION: The major prevalence of antibiotic resistant strains of S.
      aureus combined with the lack of new antibiotic discoveries highlight the need
      for vigorous research into alternative strategies to combat diseases caused by
      this highly successful pathogen. Current efforts to develop specific
      antivirulence strategies, vaccine approaches, and alternative therapies for
      treating severe disease caused by S. aureus have the potential to stem the tide
      against the limitations that we face in the post-antibiotic era.

PMID- 27894244
TI  - Umbelliferone Decreases Intracellular pH and Sensitizes Melanoma Cell Line A375
      to Dacarbazin. Comparison with Acetazolamide.
AB  - BACKGROUND AND OBJECTIVE: The high degree of malignancy of tumour cells is linked
      to alterations of many physiological parameters like the intracellular pH (pHi).
      The pHi in cancer cell line is regulated by the carbonic anhydrase IX (CA IX).
      The main enzymatic function of the CA IX protein is to catalyze the hydration of
      carbon dioxide into bicarbonate ions and protons. CA IX expression in a broad
      variety of human tumor tissues is associated with resistance to therapy. One
      promising approach is to target the mechanism regulating pH homeostasis with
      carbonic anhydrase inhibitors like sulfamides and coumarins families. METHODS: In
      this work we have evaluated effects of umbelliferone and acetazolamide in a high
      resistant melanoma cell line (A375) over expressing CA IX. Impact of effective
      doses of CA IX inhibitors on apoptosis, intracellular pH (pHi), CA IX protein
      expression and functionality have been investigated. Determination of effective
      doses of CA IX inhibitors was performed with MTT tests. We also evaluated
      sensitization effect of CA inhibitors to conventional therapy as dacarbazin.
      RESULTS: We have used 10 uM Umbelliferone and 100 uM Acetazolamide as effective
      doses for 24h. These doses did not induce any apoptosis. Umbelliferone induced a
      more important pHi decrease than Acetalozamide from 7.3 to 7.08 and to 7.12
      respectively, and a more important decrease in s-CA IX fraction showing a
      decrease in CA IX function. We have demonstrated that pre-treatment with
      umbelliferone or acetazolamide allows a better dacarbazin efficacy. CONCLUSION:
      We have demonstrated that inhibitors modify intracellular pH and CAIX
      functionality and sensitize cells to Dacarbazin. These original results complete
      the knowledge on Sulfamide CA IX inhibitors, bring new insights about Coumarin
      compounds and offer new possibilities in high grade melanoma therapies.

PMID- 27894243
TI  - Spinal Muscular Atrophy: More than a Disease of Motor Neurons?
AB  - Spinal muscular atrophy (SMA) is the most common genetically inherited
      neurodegenerative disease resulting in infant mortality. SMA is caused by genetic
      deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results
      in reduced levels of the survival of motor neuron (SMN) protein. SMN protein
      deficiency preferentially affects alpha- motor neurons, leading to their
      degeneration and subsequent atrophy of limb and trunk muscles, progressing to
      death in severe forms of the disease. More recent studies have shown that SMN
      protein depletion is detrimental to the functioning of other tissues including
      skeletal muscle, heart, autonomic and enteric nervous systems,
      metabolic/endocrine (e.g. pancreas), lymphatic, bone and reproductive system. In
      this review, we summarize studies discussing SMN protein's function in various
      cell and tissue types and their involvement in the context of SMA disease
      etiology. Taken together, these studies indicate that SMA is a multi-organ
      disease, which suggests that truly effective disease intervention may require
      body-wide correction of SMN protein levels.

PMID- 27894242
TI  - Indazolo[3,2-b]quinazolinones Attack Hepatocellular Carcinoma Hep3B Cells by
      Inducing Mitochondrial-Dependent Apoptosis and Inhibition of Nrf2/ARE Signaling
      Pathway.
AB  - BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) is the second leading
      cause of cancer death worldwide. Genotoxic stress resistance in patients often
      contributes to poor clinical outcomes, and is intensively associated to the
      upregulation of Nrf2/ARE signaling pathway. In this study, we examined the
      connection between the anticancer activity of two novel indazolo[3,2
      b]quinazolinone (IQ) derivatives, IQ-7 and IQ-12, and their effect on the
      Nrf2/ARE signaling pathway. METHODS: We initially measured the cytotoxicity of IQ
      7 and IQ-12 in Hep3B (human hepatoma cell) and HL-7702 (normal human liver cell)
      cell lines, then further detected their effects on Nrf2/ARE signaling pathway and
      apoptosis. RESULTS: IQ-7 and IQ-12 downregulated the expression levels of Nrf2
      and its downstream target genes, such as NQO1, HO-1 and Gclc. In Hep3B cells
      treated with IQ-7 or IQ-12, the mitochondrial membrane potential decreased
      dramatically while the expression level of the pro-apoptotic protein VDAC1 and
      anti-apoptotic protein Bcl-2 significantly increased and decreased, respectively.
      In addition, IQ-7 (but not IQ-12) also induced the activity of Caspase-3.
      Interestingly, IQ-7 appeared to selectively inhibit Hep3B cells while having rare
      adverse effect on HL-7702 cells. CONCLUSION: The two compounds were shown to
      induce apoptosis and inhibit the Nrf2/ARE signaling pathway in Hep3B cells, and
      IQ-7 was suggested a degree of specificity against cancer cells. The design of
      these compounds may therefore represent a new strategy for designing quinazoline
      derivatives that could selectively target carcinoma cells.

PMID- 27894245
TI  - Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism
      and Efflux Transport.
AB  - BACKGROUND: Mechanistic understanding of the metabolism-transport interplay
      assumes great importance in pharmaceutical fields because the knowledge can help
      to interpret drug/xenobiotic metabolism and disposition studies as well as the
      drug-drug interactions in vivo. About 10 years ago, it started to recognize that
      cellular phase II metabolism is strongly influenced by the excretion (efflux
      transport) of generated metabolites, a kinetic phenomenon termed "phase II
      metabolism-transport interplay". This interplay is believed to have significant
      effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing
      phase II metabolism. METHODS: In this article, we review the studies
      investigating the phase II metabolism-transport interplay using cell models,
      perfused rat intestine, and intact rats. The potential confounding factors in
      exploring such interplay is also summarized. Moreover, the mechanism underlying
      the phase II metabolism-transport interplay is discussed. RESULTS: Various
      studies with engineered cells and rodents have demonstrated that there is an
      interaction (interplay) between phase II enzymes and efflux transporters. This
      type of interplay mainly refers to the dependence of phase II (conjugative)
      metabolism on the activities of efflux transporters. In general, inhibiting
      efflux transporters or decreasing their expression causes the reductions in
      metabolite excretion, apparent excretion clearance (CLapp) and total metabolism
      (fmet), as well as an increase in the intracellular level of metabolite (Ci). The
      deconjugation mediated by hydrolase (acting as a "bridge") is essential for the
      interplay to play out based on pharmacokinetic modeling/simulations, cell and
      animal studies. The hydrolases bridge the two processes (i.e., metabolite
      formation and excretion) and enable the interplay thereof (a bridging effect).
      Without the bridge, metabolite formation is independent on its downstream process
      excretion, thus impact of metabolite excretion on its formation is impossible.
      CONCLUSION: Deconjugation (mediated by hydrolases) plays an essential role in the
      conjugation-transport interplay.

PMID- 27894246
TI  - N-Chlorosuccinimide-Mediated Oxidative Chlorination of Thiols to Nalpha 
      Protected Amino Alkyl Sulfonyl Azides and Their Utility in the Synthesis of
      Sulfonyl Triazole Acids
AB  - An efficient oxidative chlorination of thiols to Nalpha-protected amino alkyl
      sulfonyl azides isdelineated. The reaction involves in situ generation of
      sulfonyl chloride employing Nchlorosuccinimideand tetrabutylammonium chloride
      water in acetonitrile, followed by the reactionwith sodium azide. The protocol is
      simple, straight forward, mild and high yielding. Amino acidswith simple as well
      as bifunctional side chains were used to obtain Nalpha-protected amino alkyl
      sulfonylazides. Further, sulfonyl azides were utilized to synthesize unnatural
      amino acids viaCu(OAc)2.H2O/2-amino phenol catalyzed Click reaction with
      propiolic acid.

PMID- 27894247
TI  - Aldose Reductase as a Drug Target for Treatment of Diabetic Nephropathy: Promises
      and Challenges.
AB  - Diabetic nephropathy (DN) is one of the most serious microvascular complications
      of diabetes mellitus and the leading cause of end stage renal disease. One of the
      key pathways activated in DN is the polyol pathway, in which glucose is converted
      to sorbitol (a relatively nonmetabolizable sugar) by the enzyme aldose reductase
      (AR). Shunting of glucose into this pathway causes disruption to glucose
      metabolism and subsequently damages the tissues via increased oxidative stress,
      protein kinase c activation and production of advanced glycation end products
      (AGE) in the kidney. This review aims to provide a comprehensive overview of the
      AR enzyme structure, substrate specificity and topology in normal physiology; to
      elaborate on the deleterious effects of AR activation in DN; and to summarize the
      potential therapeutic benefits and major challenges associated with AR inhibition
      in patients with DN.

PMID- 27894248
TI  - Crystal Structure of Murein-Tripeptide Amidase MpaA from Escherichia coli O157 at
      2.6 A Resolution.
AB  - Peptidoglycan (PG) is an essential component of the cell wall, and undergoes
      reconstruction by various PG hydrolases during cell growth, development and
      division. The murein- tripeptide (Mtp) amidase MpaA belongs to PG hydrolase
      family and is responsible for cleaving the gamma-D-Glumeso- Dap amide bond in the
      Mtp released during PG turnover. The current paper reports the crystal structure
      of MpaA from Escherichia coli (E. coli) O157 at 2.6 A resolution. The asymmetric
      unit consists of two protein molecules and each monomer represents the common
      alpha/beta fold of metallocarboxypeptidases (MCP). The Tyr133-Asp143 loop appears
      to mediate the entrance and binding of the substrate into the active groove. A
      structural comparison of MpaA with its homologue from Vibrio harveyi showed that
      MpaA has narrower active pocket entrance with a smaller surface opening, which is
      determined by the Val204-Thr211 loop. The reported structure provides a starting
      point for the molecular mechanism of MpaA in a significant human pathogen.

PMID- 27894249
TI  - Brief compression-only cardiopulmonary resuscitation training video and
      simulation with homemade mannequin improves CPR skills.
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR) training has traditionally
      involved classroom-based courses or, more recently, home-based video self
      instruction. These methods typically require preparation and purchase fee; which
      can dissuade many potential bystanders from receiving training. This study aimed
      to evaluate the effectiveness of teaching compression-only CPR to previously
      untrained individuals using our 6-min online CPR training video and skills
      practice on a homemade mannequin, reproduced by viewers with commonly available
      items (towel, toilet paper roll, t-shirt). METHODS: Participants viewed the
      training video and practiced with the homemade mannequin. This was a parallel
      design study with pre and post training evaluations of CPR skills (compression
      rate, depth, hand position, release), and hands-off time (time without
      compressions). CPR skills were evaluated using a sensor-equipped mannequin and
      two blinded CPR experts observed testing of participants. RESULTS: Twenty-four
      participants were included: 12 never-trained and 12 currently certified in CPR.
      Comparing pre and post training, the never-trained group had improvements in
      average compression rate per minute (64.3 to 103.9, p = 0.006), compressions with
      correct hand position in 1 min (8.3 to 54.3, p = 0.002), and correct compression
      release in 1 min (21.2 to 76.3, p < 0.001). The CPR-certified group had adequate
      pre and post-test compression rates (>100/min), but an improved number of
      compressions with correct release (53.5 to 94.7, p < 0.001). Both groups had
      significantly reduced hands-off time after training. Achieving adequate
      compression depths (>50 mm) remained problematic in both groups. Comparisons made
      between groups indicated significant improvements in compression depth, hand
      position, and hands-off time in never-trained compared to CPR-certified
      participants. Inter-rater agreement values were also calculated between the CPR
      experts and sensor-equipped mannequin. CONCLUSIONS: A brief internet-based video
      coupled with skill practice on a homemade mannequin improved compression-only CPR
      skills, especially in the previously untrained participants. This training method
      allows for widespread compression-only CPR training with a tactile learning
      component, without fees or advance preparation.

PMID- 27894250
TI  - Pathological interactions between the endothelin-1 and the angiotensin-
      converting enzyme among Tunisian coronary patients.
AB  - BACKGROUND: The correct understanding of the biochemical and metabolic
      interactions between coronary risk factors contribute to the exploration of
      cardiovascular pathophysiology and improves therapeutic care. The aim of this
      study was to explore the endothelin-1 (ET-1) concentration and the angiotensin
      converting enzyme (ACE) activity among Tunisian patients with coronary heart
      disease, and to investigate the metabolic relationships between these two
      markers,... and to assess the possible relationship between them and the
      different risk factors. In this present study, ET-1 concentration was determined
      by an analytical method (High Performance Chromatography, coupled by Mass
      Spectrometry), ACE activity was measured by a kinetic method for patients and
      healthy controls. These subjects (157 patients and 142 controls) beneficed also
      by a biochemical exploration (lipid, apolipoproteins and glucose profiles) to
      quantify cardiovascular risk. RESULTS: A statistically significant increase of
      the ET-1 concentration was found among patients compared to healthy controls
      (15.2 +/- 5.3 nM vs 7.1 +/- 2.7 nM, p < 0,00001). For the ACE activity, in spite
      the treatment of the majority of patients (97%) with ACE inhibitors, this
      activity was statistically elevated in patients compared to healthy subjects
      (86.7 +/- 25.4 IU/L vs 42.8 +/- 12.1 IU/L, p < 0.00001). Furthermore, a
      statistically positive correlation was identified between these two cardiac
      markers (r = 0.68 p < 0.00001). CONCLUSION: The study of the metabolic
      relationship between the ET-1 and ACE among coronary patients reveals other
      therapeutics targets.

PMID- 27894251
TI  - Comprehensive analysis of the fecal microbiota of healthy Japanese adults reveals
      a new bacterial lineage associated with a phenotype characterized by a high
      frequency of bowel movements and a lean body type.
AB  - BACKGROUND: In Japan, a variety of traditional dietary habits and daily routines
      have developed in many regions. The effects of these behaviors, and the regional
      differences in the composition of the gut microbiota, are yet to be sufficiently
      studied. To characterize the Japanese gut microbiota and identify the factors
      shaping its composition, we conducted 16S metagenomics analysis of fecal samples
      collected from healthy Japanese adults residing in various regions of Japan. Each
      participant also completed a 94-question lifestyle questionnaire. RESULTS: We
      collected fecal samples from 516 healthy Japanese adults (325 females, 191 males;
      age, 21-88). Heatmap and biplot analyses based on the bacterial family
      composition of the fecal microbiota showed that subjects' region of residence or
      gender were not strongly correlated with the general composition of the fecal
      microbiota. Although clustering analysis for the whole cohort did not reveal any
      distinct clusters, two enterotype-like clusters were observed in the male, but
      not the female, subjects. In the whole subject population, the scores for bowel
      movement frequency were significantly correlated with the abundances of
      Christensenellaceae, Mogibacteriaceae, and Rikenellaceae in the fecal microbiota
      (P < 0.001). These three bacterial families were also significantly more abundant
      (P < 0.05 or 0.01) in lean subjects (body mass index (BMI) < 25) than in obese
      subjects (BMI > 30), which is consistent with previously published results.
      However, a previously reported correlation between BMI and bowel movement
      frequency was not observed. In addition, the abundances of these three families
      were positively correlated with each other and comprised a correlative network
      with 14 other bacterial families. CONCLUSIONS: The present study showed that the
      composition of the fecal microbiota of healthy Japanese adults at the national
      level was not strongly correlated with subjects' area of residence or gender. In
      addition, enterotype partitioning was ambiguous in this cohort of healthy
      Japanese adults. Finally, the results implied that the abundances of
      Christensenellaceae, Mogibacteriaceae, and Rikenellaceae, along with several
      other bacterial components that together comprised a correlative network,
      contributed to a phenotype characterized by a high frequency of bowel movements
      and a lean body type.

PMID- 27894252
TI  - Transcriptome analysis reveals the genetic basis underlying the seasonal
      development of keratinized nuptial spines in Leptobrachium boringii.
AB  - BACKGROUND: The expression of sexually selected traits often varies with
      populations' breeding cycles in many animals. The elucidation of mechanisms
      underlying the expression of such traits is a research topic in evolutionary
      biology; however, the genetic basis of the seasonal development of their
      expression remains unknown. Male Leptobrachium boringii develop keratinized
      nuptial spines on their upper jaw during the breeding season that fall off when
      the breeding season ends. To illuminate the genetic basis for the expression of
      this trait and its seasonal development, we assessed the de novo transcriptome
      for L. boringii using brain, testis and upper jaw skin and compared gene
      expression profiles of these tissues between two critical periods of the spine
      growth cycle. RESULTS: We identified 94,900 unigenes in our transcriptome. Among
      them, 2,131 genes were differentially expressed between the breeding period when
      the spines developed and the post-breeding period when the spines were sloughed.
      An increased number of differentially expressed genes (DEGs) were identified in
      the upper jaw skin compared with the testis and brain. In the upper jaw skin,
      DEGs were mainly enriched in cytosolic part, peptidase inhibitor activity and
      peptidase regulator activity based on GO enrichment analysis and in
      glycolysis/gluconeogenesis, ribosome biogenesis in eukaryotes and retinol
      metabolism based on KEGG enrichment analysis. In the other two tissues, DEGs were
      primarily involved in the cell cycle, DNA replication and melatonin production.
      Specifically, insulin/insulin-like growth factor and sex steroid hormone-related
      DEGs were identified in the upper jaw skin, indicating . The expression variation
      of IGF2 and estrogen-related genes may be the main factors regulating the
      seasonal development of the spines. CONCLUSIONS: Our study provides a list of
      potential genes involved in the regulation of seasonal development of nuptial
      spines in L. boringii. This is the first transcriptome survey of seasonally
      developed sexually selected traits for non-model amphibian species, and candidate
      genes provided here may provide valuable information for further studies of L.
      boringii.

PMID- 27894253
TI  - Latitudinal clines in gene expression and cis-regulatory element variation in
      Drosophila melanogaster.
AB  - BACKGROUND: Organisms can rapidly adapt to their environment when colonizing a
      new habitat, and this could occur by changing protein sequences or by altering
      patterns of gene expression. The importance of gene expression in driving local
      adaptation is increasingly being appreciated, and cis-regulatory elements (CREs),
      which control and modify the expression of the nearby genes, are predicted to
      play an important role. Here we investigate genetic variation in gene expression
      in immune-challenged Drosophila melanogaster from temperate and tropical or sub
      tropical populations in Australia and United States. RESULTS: We find parallel
      latitudinal changes in gene expression, with genes involved in immunity,
      insecticide resistance, reproduction, and the response to the environment being
      especially likely to differ between latitudes. By measuring allele-specific gene
      expression (ASE), we show that cis-regulatory variation also shows parallel
      latitudinal differences between the two continents and contributes to the
      latitudinal differences in gene expression. CONCLUSIONS: Both Australia and
      United States were relatively recently colonized by D. melanogaster, and it was
      recently shown that introductions of both African and European flies occurred,
      with African genotypes contributing disproportionately to tropical populations.
      Therefore, both the demographic history of the populations and local adaptation
      may be causing the patterns that we see.

PMID- 27894254
TI  - Divergent selection-induced obesity alters the composition and functional
      pathways of chicken gut microbiota.
AB  - BACKGROUND: The gastrointestinal tract is populated by a complex and vast
      microbial network, with a composition that reflects the relationships of the
      symbiosis, co-metabolism, and co-evolution of these microorganisms with their
      host. The mechanism that underlies such interactions between the genetics of the
      host and gut microbiota remains elusive. RESULTS: To understand how genetic
      variation of the host shapes the gut microbiota and interacts with it to affect
      the metabolic phenotype of the host, we compared the abundance of microbial taxa
      and their functional performance between two lines of chickens (fat and lean)
      that had undergone long-term divergent selection for abdominal fat pad weight,
      which resulted in a 4.5-fold increase in the fat line compared to the lean line.
      Our analysis revealed that the proportions of Fusobacteria and Proteobacteria
      differed significantly between the two lines (8 vs. 18% and 33 vs. 24%,
      respectively) at the phylum level. Eight bacterial genera and 11 species were
      also substantially influenced by the host genotype. Differences between the two
      lines in the frequency of host alleles at loci that influence accumulation of
      abdominal fat were associated with differences in the abundance and composition
      of the gut microbiota. Moreover, microbial genome functional analysis showed that
      the gut microbiota was involved in pathways that are associated with fat
      metabolism such as lipid and glycan biosynthesis, as well as amino acid and
      energy metabolism. Interestingly, citrate cycle and peroxisome proliferator
      activated receptor (PPAR) signaling pathways that play important roles in lipid
      storage and metabolism were more prevalent in the fat line than in the lean line.
      CONCLUSIONS: Our study demonstrates that long-term divergent selection not only
      alters the composition of the gut microbiota, but also influences its functional
      performance by enriching its relative abundance in microbial taxa. These results
      support the hypothesis that the host and gut microbiota interact at the genetic
      level and that these interactions result in their co-evolution.

PMID- 27894255
TI  - Silent diabetic cardiomyopathy in everyday practice: a clinical and
      echocardiographic study.
AB  - BACKGROUND: Whether type 2 diabetes mellitus (DM) in the absence of hypertension
      (HTA) and coronary artery disease (CAD) affects left ventricular (LV) phenotype
      and function among asymptomatic DM patients that can be easily discovered in
      everyday practice, what is the clinical risk profile for diabetic cardiomyopathy
      and how HTA and CAD modulate LV structure and function above diabetic
      cardiomyopathy, are still incompletely answered questions. METHODS: In 210 DM
      patients (group I: 70 asymptomatic DM patients without HTA and CAD; group II: 70
      DM patients with HTA and no CAD; group III: 70 DM patients with CAD and no HTA)
      and 80 healthy individuals, comprehensive echocardiography including speckle
      tracking strain and strain rate analysis, was done. RESULTS: Compared to control
      DM patients without HTA and CAD had increased LV mass, more frequently concentric
      remodeling, impaired LV relaxation and lower LV ejection fraction (EF), fraction
      of shortening (FS) and mitral annular plane excursion (MAPSE). Addition of HTA
      further impaired EF, FS and MAPSE and aggravated diastolic dysfunction, whereas
      concomitant CAD further impaired FS and MAPSE. Peak global longitudinal strain
      (Slong) and early diastolic longitudinal strain rate (SRlong E) were impaired in
      group I compared to control, even when EF was preserved. Peak circumferential
      strain (Scirc) was impaired only when DM was associated with HTA or CAD. In
      multivariate analysis DM was significantly and independently from HTA, CAD, age,
      gender and body mass index associated with: increased LV mass, concentric LV
      remodeling, lower EF, FS, MAPSE, Slong, SRlongE and distorted diastolic
      parameters. DM duration, glycosylated hemoglobin, microalbuminuria and
      retinopathy, were not independent predictors of LV geometry and function.
      CONCLUSION: DM per se has strong and independent influence on LV phenotype and
      function that can be detected by conventional and speckle tracking
      echocardiography in everyday clinical practice, even in asymptomatic patients. We
      could not confirm that these changes were independently related to duration of
      DM, quality of metabolic control and presence of microvascular complications.
      Concomitant HTA or CAD furthermore distorted LV systolic and diastolic function.

PMID- 27894256
TI  - Burkholderia pseudomallei-derived miR-3473 enhances NF-kappaB via targeting TRAF3
      and is associated with different inflammatory responses compared to Burkholderia
      thailandensis in murine macrophages.
AB  - BACKGROUND: Burkholderia pseudomallei (Bp) is the causative agent of melioidosis,
      a kind of tropical disease. Burkholderia thailandensis (Bt), with a high sequence
      similarity to Bp, is thought to be an avirulent organism. Since there are
      numerous similarities between Bp and Bt, their differences in pathogenesis of
      host response and related mechanism are still undermined. In recent years,
      microRNAs have been researched in many diseases, but seldom involved in bacterial
      infection, bacteria-host interaction or explaining the differences between
      virulent and avirulent species. RESULTS: We found that Bp and Bt had similar
      phenotypes in terms of intracellular replication, dissemination (reflected by
      multinucleated giant cell formation), TNF-alpha release and apoptosis in RAW264.7
      macrophages or TC-1 pulmonary cell but in different level. Especially, at the
      late infection phases (after 12 h post infection), Bp showed faster intracellular
      growth, stronger cytotoxicity, and higher TNF-alpha release. After microRNA array
      analysis, we found some microRNAs were significantly expressed in macrophages
      treated by Bp. miR-3473 was one of them specifically induced, but not
      significantly changed in Bt-treated macrophages. In addition, TargetScan
      suggested that miR-3473 possibly target TRAF3 (TNF receptor-associated factor 3),
      a well-known negative regulator of the NF-kappaB pathway, which was probably
      involved in the TNF-alpha induction and apoptosis in cells with Bp infection. In
      vivo, it was found that miR-3473 expression of total lungs cells from Bp-treated
      was higher than that from Bt-treated mice. And miR-3473 inhibitor was able to
      decrease the TNF-alpha release of mice and prolong the survival of mice with Bp
      infection. CONCLUSION: In sum, miR-3473 plays an important role in the
      differential pathogenicity of Bp and Bt via miR-3473-TRAF3-TNF-alpha network, and
      regulates TNF-alpha release, cell apoptosis and animal survival after Bp
      treatment. In this study, we have found a specific microRNA is related to
      bacterial virulence and provide insight into the mechanism for host-bacteria
      interaction, which suggests that potential oligonucleotides should be applied
      against bacterial infection.

PMID- 27894258
TI  - Multidimensional construct of life satisfaction in older adults in Korea: a six
      year follow-up study.
AB  - BACKGROUND: Aging raises wide-ranging issues within social, economic, welfare,
      and health care systems. Life satisfaction (LS) is regarded as an indicator of
      quality of life which, in turn, is associated with mortality and morbidity in
      older adults. The objective of this study was to identify the relevant predictors
      of life satisfaction and to investigate changes in a multidimensional construct
      of LS over time. METHODS: This analysis utilized data from the large-scale,
      nationally representative Korean Retirement and Income Study (KReIS), a
      longitudinal survey conducted biennially from 2005 to 2011. Outcome measures were
      degree of satisfaction with health, economic status, housing, neighbor
      relationships, and family relationships. GEE models were used to investigate
      changes in satisfaction within each of the five domains. RESULTS: Of a total 3531
      individuals aged 65 or older, 2083 (59%) were women, and the mean age was 72 (s.d
      = +/-6) years. The majority had a spouse (60.8%) and lived in a rural area (58%).
      Analysis showed that physical and mental health were consistently and
      significantly associated with satisfaction in each of the domains after adjusting
      for potential confounders. Living in a rural area and living with a spouse were
      related to satisfaction with economic, housing, family relationships, and
      neighbor relationships compared to living in urban areas and living without a
      spouse; the only outcome that did not show relationship to these predictors was
      health satisfaction. Female and rural residents reported greater economic
      satisfaction compared to male and urban residents. Living in an apartment was
      associated with 1.32 times greater odds of economic satisfaction compared to
      living in a detached house (95% CI: 1.14-1.53; p < 0.0001). Economic satisfaction
      was also 1.62 times more likely among individuals living with a spouse compared
      to single households (95% CI: 1.35-1.96; p < 0.0001). Financial stress index
      value was found to be a significant predictor of satisfaction with family
      relationships. CONCLUSIONS: Our study indicates that a single domain of LS or
      overall LS will miss many important aspects of LS as age-related LS is multi
      faceted and complicated. While most studies focus on overall life satisfaction,
      considering life satisfaction as multidimensional is essential to gaining a
      complete picture.

PMID- 27894257
TI  - Evidence of functional divergence in MSP7 paralogous proteins: a molecular
      evolutionary and phylogenetic analysis.
AB  - BACKGROUND: The merozoite surface protein 7 (MSP7) is a Plasmodium protein which
      is involved in parasite invasion; the gene encoding it belongs to a multigene
      family. It has been proposed that MSP7 paralogues seem to be functionally
      redundant; however, recent experiments have suggested that they could have
      different roles. RESULTS: The msp7 multigene family has been described in newly
      available Plasmodium genomes; phylogenetic relationships were established in 12
      species by using different molecular evolutionary approaches for assessing
      functional divergence amongst MSP7 members. Gene expansion and contraction rule
      msp7 family evolution; however, some members could have had concerted evolution.
      Molecular evolutionary analysis showed that relaxed and/or intensified selection
      modulated Plasmodium msp7 paralogous evolution. Furthermore, episodic
      diversifying selection and changes in evolutionary rates suggested that some
      paralogous proteins have diverged functionally. CONCLUSIONS: Even though msp7 has
      mainly evolved in line with a birth-and-death evolutionary model, gene conversion
      has taken place between some paralogous genes allowing them to maintain their
      functional redundancy. On the other hand, the evolutionary rate of some MSP7
      paralogs has become altered, as well as undergoing relaxed or intensified
      (positive) selection, suggesting functional divergence. This could mean that some
      MSP7s can form different parasite protein complexes and/or recognise different
      host receptors during parasite invasion. These results highlight the importance
      of this gene family in the Plasmodium genus.

PMID- 27894260
TI  - High platelet reactivity affects the clinical outcomes of patients undergoing
      percutaneous coronary intervention.
AB  - BACKGROUND: The association of platelet reactivity and clinical outcomes,
      especially stent thrombosis, was not so clear. We sought to investigate whether
      high platelet reactivity affects clinical outcomes of patients with drug eluting
      stents (DESs) implantation. METHODS: All enrolled individuals treated with DESs
      implantation were evaluated by PL-11, using sequentially platelet counting
      method. The primary end point was the occurrence of definite and probable stent
      thrombosis at 2 years. The secondary endpoint was major adverse cardiovascular
      and cerebrovascular events (MACCE), including all cause death, spontaneous
      myocardial infarction (MI), target vessel revascularization (TVR), and ischemic
      stroke. RESULTS: A total of 1331consecutive patients were enrolled at our center.
      There were 91 patients (6.8 %) identified with high platelet reactivity (HPR) on
      aspirin, and 437 patients (32.9 %) with HPR on clopidogrel. At 2-year follow-up,
      the incidence of stent thrombosis was significantly higher in patients with HPR
      on aspirin (9.9 % vs. 0.4 %, p < 0.001), and HPR on clopidogrel (3.0 % vs. 0.1 %,
      p < 0.001). There were increased MACCE in the HPR on aspirin group (16.5 % vs.
      8.5 %, p = 0.021), mainly driven by the higher all cause death (7.7 % vs. 1.6 %,
      p = 0.002) and MI (9.9 % vs. 1.9 %, p < 0.001) in the HPR on aspirin group.
      Similarly, the rate of MACCE was higher in the HPR on clopidogrel group (12.4 %
      vs. 7.4 %, p = 0.004). No differences in all bleeding and hemorrhagic stroke were
      observed. CONCLUSIONS: The present study demonstrated that high platelet
      reactivity on both aspirin and clopidogrel were associated with incremental stent
      thrombosis following DESs implantation.

PMID- 27894259
TI  - Genomic signatures of Mannheimia haemolytica that associate with the lungs of
      cattle with respiratory disease, an integrative conjugative element, and
      antibiotic resistance genes.
AB  - BACKGROUND: Mannheimia haemolytica typically resides in cattle as a commensal
      member of the upper respiratory tract microbiome. However, some strains can
      invade their lungs and cause respiratory disease and death, including those with
      multi-drug resistance. A nucleotide polymorphism typing system was developed for
      M. haemolytica from the genome sequences of 1133 North American isolates, and
      used to identify genetic differences between isolates from the lungs and upper
      respiratory tract of cattle with and without clinical signs of respiratory
      disease. RESULTS: A total of 26,081 nucleotide polymorphisms were characterized
      after quality control filtering of 48,403 putative polymorphisms. Phylogenetic
      analyses of nucleotide polymorphism genotypes split M. haemolytica into two major
      genotypes (1 and 2) that each were further divided into multiple subtypes.
      Multiple polymorphisms were identified with alleles that tagged genotypes 1 or 2,
      and their respective subtypes. Only genotype 2 M. haemolytica associated with the
      lungs of diseased cattle and the sequence of a particular integrative and
      conjugative element (ICE). Additionally, isolates belonging to one subtype of
      genotype 2 (2b), had the majority of antibiotic resistance genes detected in this
      study, which were assorted into seven combinations that ranged from 1 to 12
      resistance genes. CONCLUSIONS: Typing of diverse M. haemolytica by nucleotide
      polymorphism genotypes successfully identified associations with diseased cattle
      lungs, ICE sequence, and antibiotic resistance genes. Management of cattle by
      their carriage of M. haemolytica could be an effective intervention strategy to
      reduce the prevalence of respiratory disease and supplemental needs for
      antibiotic treatments in North American herds.

PMID- 27894262
TI  - Erratum to: Statistical methodology for age-adjustment of the GH-2000 score
      detecting growth hormone misuse.

PMID- 27894263
TI  - Erratum to: A new transcriptome and transcriptome profiling of adult and larval
      tissue in the box jellyfish Alatina alata: an emerging model for studying venom,
      vision and sex.

PMID- 27894261
TI  - Multimarker approach for the prediction of microvascular obstruction after acute
      ST-segment elevation myocardial infarction: a prospective, observational study.
AB  - BACKGROUND: Presence of microvascular obstruction (MVO) derived from cardiac
      magnetic resonance (CMR) imaging is among the strongest outcome predictors after
      ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the
      comparative predictive values of different biomarkers for the occurrence of MVO
      in a large cohort of reperfused STEMI patients. METHODS: This study included 128
      STEMI patients. CMR imaging was performed within the first week after infarction
      to assess infarct characteristics, including MVO. Admission and peak
      concentrations of high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase
      (CK), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C
      reactive protein (hs-CRP), lactate dehydrogenase (LDH), aspartate transaminase
      (AST) and alanine transaminase (ALT) were measured. RESULTS: MVO was detected in
      69 patients (54%). hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations
      showed similar prognostic value for the prediction of MVO (area under the curve
      (AUC) = 0.77, 0.77, 0.68, 0.79, 0.78 and 0.73, all p > 0.05), whereas the
      prognostic utility of NT-proBNP was weakly lower (AUC = 0.64, p < 0.05).
      Combination of these biomarkers did not increase predictive utility compared to
      hs-cTnT alone (p = 0.349). CONCLUSIONS: hs-cTnT, CK, hs-CRP, LDH, AST and ALT
      peak concentrations provided similar prognostic value for the prediction of MVO.
      The prognostic utility of NT-proBNP was lower. Combining these biomarkers could
      not further improve predictive utility compared to hs-cTnT alone.

PMID- 27894264
TI  - Optical coherence tomography findings after longitudinal ablation for an
      underexpanded stent in a heavily calcified lesion: a case report.
AB  - BACKGROUND: Heavy coronary artery calcification is responsible for stent
      underexpansion, which is associated with increased in-stent restenosis. Here we
      report a case in which optical coherence tomography (OCT) demonstrated that the
      metal component of an underexpanded stent previously implanted in a heavy
      calcified lesion had been completely removed after ablation with rotational
      atherectomy. CASE PRESENTATION: An 83-year-old man with exertional angina was
      referred to our hospital. Coronary angiography revealed severe stenosis in the
      proximal portion of the right coronary artery and left circumflex artery and
      chronic total occlusion (CTO) in the mid portion of the left anterior descending
      artery (LAD). We performed complete revascularization with percutaneous coronary
      intervention. Because the CTO lesion in LAD contained napkin-ring heavy
      calcifications, rotational atherectomy with a 1.75-mm burr was undergone,
      followed by the deployment of drug-eluting stents and postdilation with a high
      pressure balloon. However, expansion of the stent was incomplete. To address the
      recurrence of in-stent restenosis and resistance to the dilation with the high
      pressure balloon, we decided to simultaneously ablate both the heavy
      calcification and underexpanded stent. Longitudinal stent ablation with 1.75- and
      2.0-mm burrs was successful, and OCT demonstrated that the metallic component of
      the underexpanded stent had been completely removed. CONCLUSION: If a stent fails
      to completely extend in heavy calcification, longitudinal stent ablation by
      rotational atherectomy could be an effective remedy.

PMID- 27894265
TI  - Long term condition morbidity in English general practice: a cross-sectional
      study using three composite morbidity measures.
AB  - BACKGROUND: The burden of morbidity represented by patients with long term
      conditions (LTCs) varies substantially between general practices. This study
      aimed to determine the characteristics of general practices with high morbidity
      burden. METHOD: Retrospective cross-sectional study; general practices in
      England, 2014/15. Three composite morbidity measures (MMs) were constructed to
      quantify LTC morbidity at practice level: a count of LTCs derived from the 20
      LTCs included in the UK Quality and Outcomes Framework (QOF) disease registers,
      expressed as 'number of QOF LTCs per 100 registered patients'; the % of patients
      with one or more QOF LTCs; the % of patients with one or more of 15 broadly
      defined LTCs included in the GP Patient Survey (GPPS). Determinants of MM scores
      were analysed using multi-level regression models. Analysis was based on a
      national dataset of English general practices (n = 7779 practices); GPPS
      responses (n = 903,357); general practice characteristics (e.g. list size, list
      size per full time GP); patient demographic characteristics (age, deprivation
      status); secondary care utilisation (out-patient, emergency department, emergency
      admission rates). RESULTS: Mean MM scores (95% CIs) were: 57.7 (+/-22.3) QOF LTCs
      per 100 registered patients; 22.8% (+/-8.2) patients with a QOF LTC; 63.5% (+/
      11.7) patients with a GPPS LTC. The proportion of elderly patients and social
      deprivation scores were the strongest predictors of each MM score; scores were
      largely independent of practice characteristics. MM scores were positive
      predictors of secondary care utilization and negative predictors' access,
      continuity of care and overall satisfaction. CONCLUSIONS: Wide variation in LTC
      morbidity burden was observed across English general practice. Variation was
      determined by demographic factors rather than practice characteristics. Higher
      rates of secondary care utilisation in practices with higher morbidity burden
      have implications for resource allocation and commissioning budgets; lower
      reported satisfaction in these practices suggests that practices may struggle
      with increased workload. There is a need for a readily available metric to define
      the burden of morbidity and multimorbidity in general practice.

PMID- 27894266
TI  - Tuberculosis drug resistance in Bamako, Mali, from 2006 to 2014.
AB  - BACKGROUND: Although Drug resistance tuberculosis is not a new phenomenon, Mali
      remains one of the "blank" countries without systematic data. METHODS: Between
      2006 and 2014, we enrolled pulmonary TB patients from local TB diagnostics
      centers and a university referral hospital in several observational cohort
      studies. These consecutive patients had first line drug susceptibility testing
      (DST) performed on their isolates. A subset of MDR was subsequently tested for
      second line drug resistance. RESULTS: A total of 1186 mycobacterial cultures were
      performed on samples from 522 patients, including 1105 sputa and 81 blood
      samples, yielding one or more Mycobacterium tuberculosis complex (Mtbc) positive
      cultures for 343 patients. Phenotypic DST was performed on 337 (98.3%) unique
      Mtbc isolates, of which 127 (37.7%) were resistant to at least one drug,
      including 75 (22.3%) with multidrug resistance (MDR). The overall prevalence of
      MDR-TB was 3.4% among new patients and 66.3% among retreatment patients. Second
      line DST was available for 38 (50.7%) of MDR patients and seven (18.4%) had
      resistance to either fluoroquinolones or second-line injectable drugs.
      CONCLUSION: The drug resistance levels, including MDR, found in this study are
      relatively high, likely related to the selected referral population. While
      worrisome, the numbers remained stable over the study period. These findings
      prompt a nationwide drug resistance survey, as well as continuous surveillance of
      all retreatment patients, which will provide more accurate results on countrywide
      drug resistance rates and ensure that MDR patients access appropriate second line
      treatment.

PMID- 27894267
TI  - Prevalence of colonization by methicillin-resistant Staphylococcus aureus ST398
      in pigs and pig farm workers in an area of Catalonia, Spain.
AB  - BACKGROUND: A livestock-associated clonal lineage (ST398) of methicillin
      resistant Staphylococcus aureus (MRSA) has been identified causing colonization
      or infection in farm workers. The aim of the study was to analyze the prevalence
      of MRSA-ST398 colonization in pigs and in pig farmers in an area with a high pig
      population (Osona, Barcelona province, Catalonia, Spain). METHODS: We performed a
      cross-sectional prevalence study in Osona (Catalonia, Spain), from June 2014 to
      June 2015. All pig farm workers from 83 farms were studied. Twenty of these farms
      were randomly selected for the study of both pigs and farmers: 9 fattening and 11
      farrow-to-finish farms. All workers over the age of 18 who agreed to participate
      were included. Samples were analyzed to identify MRSA-ST398 and their spa type.
      RESULTS: Eighty-one of the 140 pig farm workers analyzed (57.9% (95% IC: 50.0
      66.4%)) were MRSA-positive, all of them ST398. The mean number of years worked on
      farms was 17.5 +/- 12.6 (range:1-50), without significant differences between
      positive and negative MRSA results (p = 0.763). Over 75% of MRSA-ST398 carriers
      worked on farms with more than 1250 pigs (p < 0.001). At least one worker tested
      positive for MRSA-ST398 on all 20 selected pig farms. Ninety-two (46.0% (95% IC:
      39.0-53.0%)) of the nasal swabs from 200 pigs from these 20 farms were MRSA
      positive, with 50.5% of sows and 41.4% of fattening pigs (p = 0.198) giving MRSA
      positive results. All the isolates were tetracycline-resistant, and were
      identified as MRSA-ST398. The spa type identified most frequently was t011 (62%).
      Similar spa types and phenotypes of antibiotic resistance were identified in pigs
      and farmers of 19/20 tested farms. CONCLUSIONS: The prevalence of MRSA-ST398
      among pig farm workers and pigs on farms in the studied region is very high, and
      the size of the farm seems to correlate with the frequency of colonization of
      farmers. The similar spa-types and phenotypes of resistance detected in pigs and
      workers in most of the farms studied suggest animal-to-human transmission.

PMID- 27894268
TI  - Differentiating secondary from primary dengue using IgG to IgM ratio in early
      dengue: an observational hospital based clinico-serological study from North
      India.
AB  - BACKGROUND: Secondary dengue causes more severe disease than the primary. Early
      on, it is important to differentiate the two. We tried to find important clinical
      and laboratory differences between the two for the purpose of early
      differentiation. METHODS: One hundred fourteen patients confirmed on reverse
      transcriptase-polymerase chain reaction (RT PCR) were studied. On day 2 of
      illness IgM and IgG indices were studied for calculation of IgG/IgM ratio. A one
      step immunochromatographic assay was used for classification of patients into
      primary and secondary dengue. Patient characteristics were also studied. RESULTS:
      Dengue serotype 1 was the most common found in 60.5% patients. 66.7% (76
      patients) had secondary dengue. Secondary dengue cases had a higher mean
      temperature (101.56 +/- 1.55 vs. 100.79 +/- 1.25, degrees F, p 0.015), lower
      platelet counts (50.51 +/- 38.91 vs. 100.45 +/- 38.66, x 103/micl, p <0.0001) and
      a significantly higher percentage of Dengue hemorrhagic fever/Dengue shock
      syndrome (38.2% vs. 2.6%, p <0.0001). In early phase of dengue NS1 and PCR were
      found to be better tests for diagnosis and later IgM is better. The IgG/IgM ratio
      of >= 1.10 had a sensitivity of 100%, specificity of 97.4% and accuracy of 67.5%
      in differentiating secondary from primary dengue. CONCLUSION: Early on in the
      clinical course, IgG/ IgM ratio can play an important role to differentiate the
      two. We found the ratio of >= 1.10 to be the best cut off for the same.

PMID- 27894270
TI  - Evaluation of tolerability with the co-formulation elvitegravir, cobicistat,
      emtricitabine, and tenofovir disoproxil fumarate for post-HIV exposure
      prophylaxis.
AB  - BACKGROUND: The preferred regimen for HIV post-exposure prophylaxis (PEP) is
      based mainly on safety and tolerability because it is given to immunocompetent
      people without HIV infection for a limited time (28 days). The frequency of
      adverse events (AEs) may be > 60%. Although AEs are generally not severe, they
      can lead to lack of adherence and failure to complete the regimen. We evaluated
      the co-formulation elvitegravir, cobicistat, emtricitabine, and tenofovir
      disoproxil fumarate (Stribild(r)) prescribed as one pill taken once daily for HIV
      PEP in terms of tolerability and adherence. METHODS: This was a prospective
      cohort study conducted in one hospital in Paris (April to December 2015. Each
      participant receiving the PEP treatment (FTC-150 mg/TDF-245 mg/elvitegravir-200
      mg/cobicistat 150 mg once daily) at the pharmacy of the hospital were recruited
      consecutively. A clinical visit was planned at 8 weeks after sexual exposure.
      Reminders were sent to participants who missed the appointment. A standardized
      questionnaire was administered to evaluate completeness and tolerability at week
      8. RESULTS: Overall, 284 participants (86% men; 80% MSM; median age 30 years)
      were prescribed Stribild(r); 50 stopped after reassessment of risk. Among 234
      participants who effectively received PEP, 215 (92%) completed 28 days of PEP
      with only three who switched from Stribild(r) to another PEP because of side
      effects. More than 60% of participants reported at least one AE, which were mild
      to moderate. Fatigue, central neurological and abdominal side effects were the
      most frequently reported. CONCLUSIONS: Stribild(r) seems to be a good option for
      HIV PEP due to the easiness of use, the side effects profile and the high
      completion rate.

PMID- 27894269
TI  - Prevalence of abdominal aortic aneurysms and its relation with cardiovascular
      risk stratification: protocol of the Risk of Cardiovascular diseases and
      abdominal aortic Aneurysm in Varese (RoCAV) population based study.
AB  - BACKGROUND: Recent meta-analyses suggested that screening program for abdominal
      aortic aneurysms (AAA) in 65-year old males is cost-effective at prevalence of
      about 1%. Since some events occur also in females and among the youngers,
      screening could be feasible among those at higher risk, such as smokers or
      individuals with a family history of AAA. The RoCAV (Risk of Cardiovascular
      diseases and abdominal aortic Aneurysms in Varese) Project is a population-based
      study aimed to evaluate AAA prevalence in Northern Italy in males over-65 years
      as well as among females and younger males, and to identify new markers for risk
      stratification by collecting a large set of CVD risk factors. The aims of the
      project are: (i) cross-sectional evaluation of AAA prevalence (ii); evaluation of
      standard CVD risk score as criteria for selecting subgroup at higher risk to be
      included in a screening program; (iii) identification of new risk markers and
      risk score algorithm for AAA and CVD risk stratification; (iv) cost-effective
      evaluation during the follow-up. METHODS: Males aged 50-75 years and females aged
      60-75 years, resident in the city of Varese (Lombardy Region), were randomly
      selected from the civil registry. Among 5198 successfully invited, 3777 subjects
      accepted to participate and were finally recruited (participation rate 63.8%)
      from June 2013 to May 2016. Trained operators administered a computerized
      anamnestic questionnaire, measured anthropometric parameters (BMI, body
      circumferences, skinfolds), blood pressure, ankle-brachial index, pulse wave
      velocity and performed abdominal aortic ultrasound scan, ECG and spirometry. All
      methods were internationally validated. A blood sample was collected and stored
      in biobank. A follow-up will be carried out through linkage with electronic
      records. DISCUSSION: Participation rate and data quality assessment were as
      expected and will reasonably allow to reach the project aims. The expected impact
      in public health of the RoCAV project will be the potential implementation of a
      AAA screening program to the whole region as well as the formulation of new
      criteria for risk assessment of AAA and CVD.

PMID- 27894271
TI  - Effectiveness of a physical exercise intervention program in improving functional
      mobility in older adults after hip fracture in later stage rehabilitation:
      protocol of a randomized clinical trial (REATIVE Study).
AB  - BACKGROUND: Hip fractures resulting from falls increase substantially with
      advancing age and less than half of older hip fracture survivors regain their
      former levels of mobility. There is increasing evidence that rehabilitation
      interventions with exercises that goes beyond the sub-acute phase or even in a
      later stage of care have a positive impact on various functional abilities. The
      purpose of this study is to determine if exercise program training for people who
      have suffered a fall-related hip fracture will improve functional mobility when
      compared with usual care. METHODS: A randomized controlled trial with blinded
      assessors and intention-to-treat analysis will be undertaken. We will recruit 82
      older adults, 60 years or over who have suffered a hip fracture due to a fall in
      the previous 6 to 24 months. Participants randomized to the Intervention Group
      (IG) will undertake a physical exercise program involving progressive and
      challenging balance training and neuromuscular and functional training of the
      lower limbs, conducted at home by physiotherapists, once a week, lasting about
      one hour, in the first, second and third month after randomization and will be
      taught to perform exercises at home, twice a week, using a booklet. Visits to
      monitor and progress the home exercise program will be conducted once a month,
      from the fourth to the sixth month and each 2 months until the end of the follow
      up at the 12th month, i.e., a total of 18 sessions. Participants will receive
      monthly phone calls to encourage exercise adherence. The control group will
      receive usual care. The primary outcome will be mobility-related disability and
      participants will be assessed at baseline, and at 3 months, 6 and 12 months.
      Participants will receive monthly phone calls to ask about falls and exercise
      adherence. Adverse effects will be monitored. DISCUSSION: This study proposes a
      home-based exercise program, which may in part overcome some barriers for
      rehabilitation, such as difficulties with public transportation and lack of a
      caregiver to accompany older patients to sessions. If a positive effect is
      observed this program has the potential to be incorporated into the public health
      system and contribute to building a pathway of care for older people with hip
      fracture. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02295527 .

PMID- 27894272
TI  - Clinical and molecular analyses of norovirus-associated sporadic acute
      gastroenteritis: the emergence of GII.17 over GII.4, Huzhou, China, 2015.
AB  - BACKGROUND: Noroviruses (NoVs) are the most common cause of non-bacterial acute
      gastroenteritis (AGE) in all age groups worldwide. The NoVs circulating in Huzhou
      over the past 7 years were predominantly GII.4 genotypes. In the winter of 2014
      2015, a novel variant of NoV GII.17 emerged and became predominant. We report the
      epidemiological patterns and genetic characteristics of NoV after the appearance
      of GII.17 in Huzhou City, Zhejiang, China. METHODS: Between January and December
      2015, 746 stool specimens collected from patients with acute gastroenteritis were
      screened for NoV. Real-time RT-PCR (qPCR) was performed for NoV detection. RT-PCR
      was used for genomic amplification and sequencing. Genogroups and genotypes were
      assigned using an online NoV typing tool (
      http://www.rivm.nl/mpf/norovirus/typingtool ). Phylogenetic analyses were
      conducted using MEGA (ver. 6.06). RESULTS: In total, 196 (26.3%) specimens were
      identified as NoV-positive. NoV infection was found in all age groups tested
      (<=5, 6-15, 16-40, 41-60, and >=60 years), with the 16-40-year age group having
      the highest detection rate (117/196, 59.7%). Of the 196 NoV-positive specimens,
      191 (97.5%) viruses belonged to GII, and 4 (2.0%) to GI; one sample showed GI and
      GII co-infection. Overall, 117 (59.7%) viruses were sequenced, and new
      GII.P17/GII.17 variants were the dominant genotype, accounting for 75.2%,
      followed by GII.Pe/GII.4 Sydney 2012 strains (11.11%). AGE patients infected with
      the GII.P17/GII.17 genotypes almost all had abdominal pain and watery stools.
      CONCLUSIONS: We report the epidemiological patterns and genetic characteristics
      of the emergence GII.17 over the GII.4 in Huzhou between January and December
      2015. After the emergence of GII.17 in October 2014, it steadily replaced the
      previously circulating GII.4 Sydney 2012 strain, and continued to be dominant in
      2015.

PMID- 27894273
TI  - Prevalence of non-febrile seizures in children with idiopathic autism spectrum
      disorder and their unaffected siblings: a retrospective cohort study.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a heterogeneous disorder
      characterized not only by deficits in communication and social interactions but
      also a high rate of co-occurring disorders, including metabolic abnormalities,
      gastrointestinal and sleep disorders, and seizures. Seizures, when present,
      interfere with cognitive development and are associated with a higher mortality
      rate in the ASD population. METHODS: To determine the relative prevalence of non
      febrile seizures in children with idiopathic ASD from multiplex and simplex
      families compared with the unaffected siblings in a cohort of 610 children with
      idiopathic ASD and their 160 unaffected siblings, participating in the Autism
      Genetic Resource Exchange project, the secondary analysis was performed comparing
      the life-time prevalence of non-febrile seizures. Statistical models to account
      for non-independence of observations, inherent with the data from multiplex
      families, were used in assessing potential confounding effects of age, gender,
      and history of febrile seizures on odds of having non-febrile seizures. RESULTS:
      The life-time prevalence of non-febrile seizures was 8.2% among children with ASD
      and 2.5% among their unaffected siblings. In a logistic regression analysis that
      adjusted for familial clustering, children with ASD had 5.27 (95%CI: 1.51-18.35)
      times higher odds of having non-febrile seizures compared to their unaffected
      siblings. In this comparison, age, presence of gastrointestinal dysfunction, and
      history of febrile seizures were significantly associated with the prevalence of
      non-febrile seizures. CONCLUSION: Children with idiopathic ASD are significantly
      more likely to have non-febrile seizures than their unaffected siblings,
      suggesting that non-febrile seizures may be ASD-specific. Further studies are
      needed to determine modifiable risk factors for non-febrile seizures in ASD.

PMID- 27894274
TI  - Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.
AB  - BACKGROUND: Although CRISPR/Cas enables one-step gene cassette knock-in,
      assembling targeting vectors containing long homology arms is a laborious process
      for high-throughput knock-in. We recently developed the CRISPR/Cas-based precise
      integration into the target chromosome (PITCh) system for a gene cassette knock
      in without long homology arms mediated by microhomology-mediated end-joining.
      RESULTS: Here, we identified exonuclease 1 (Exo1) as an enhancer for PITCh in
      human cells. By combining the Exo1 and PITCh-directed donor vectors, we achieved
      convenient one-step knock-in of gene cassettes and floxed allele both in human
      cells and mouse zygotes. CONCLUSIONS: Our results provide a technical platform
      for high-throughput knock-in.

PMID- 27894275
TI  - Perceived stress as a risk factor for peptic ulcers: a register-based cohort
      study.
AB  - BACKGROUND: The association between stress and peptic ulcers has been questioned
      since the discovery of helicobacter pylori. This study examined whether high
      perceived everyday life stress was associated with an increased risk of either
      receiving a triple treatment or being diagnosed with a peptic ulcer. METHODS:
      Cohen's perceived stress scale measured the level of stress in a general health
      survey in 2010 of 17,525 residents of northern Jutland, Denmark, and was linked
      with National Danish registers on prescription drugs and hospital diagnoses. Cox
      proportional hazard regression was used to estimate the risk of either receiving
      a triple treatment or being diagnosed in a hospital with a peptic ulcer, in
      relation to quintiles of stress levels. RESULTS: A total of 121 peptic ulcer
      incidents were recorded within 33 months of follow-up. The lowest stress group
      had a cumulative incidence proportion of either receiving triple treatment or
      being diagnosed with peptic ulcer of approximately 0.4%, whereas the highest
      stress group had a cumulative incidence proportion of approximately 1.2%.
      Compared with that of the lowest stress group, those in the highest stress group
      had a 2.2-fold increase in risk of either receiving triple treatment or being
      diagnosed with peptic ulcer (HR 2.24; CI 95% 1.16:4.35) after adjustment for age,
      gender, socioeconomic status, non-steroid anti-inflammatory drug use, former
      ulcer and health behaviours. There was no difference in risk between the four
      least stressed quintiles. Subgroup analysis of diagnosed peptic ulcer patients
      revealed the same pattern as the main analysis, although the results were not
      significant. CONCLUSION: The highest level of perceived everyday life stress
      raised the risk of either receiving triple treatment or being diagnosed with
      peptic ulcer during the following 33 months more than twice compared with that of
      the lowest level of perceived stress.

PMID- 27894276
TI  - Small proteins in cyanobacteria provide a paradigm for the functional analysis of
      the bacterial micro-proteome.
AB  - BACKGROUND: Despite their versatile functions in multimeric protein complexes, in
      the modification of enzymatic activities, intercellular communication or
      regulatory processes, proteins shorter than 80 amino acids (MU-proteins) are a
      systematically underestimated class of gene products in bacteria. Photosynthetic
      cyanobacteria provide a paradigm for small protein functions due to extensive
      work on the photosynthetic apparatus that led to the functional characterization
      of 19 small proteins of less than 50 amino acids. In analogy, previously
      unstudied small ORFs with similar degrees of conservation might encode small
      proteins of high relevance also in other functional contexts. RESULTS: Here we
      used comparative transcriptomic information available for two model
      cyanobacteria, Synechocystis sp. PCC 6803 and Synechocystis sp. PCC 6714 for the
      prediction of small ORFs. We found 293 transcriptional units containing candidate
      small ORFs <=80 codons in Synechocystis sp. PCC 6803, also including the known
      mRNAs encoding small proteins of the photosynthetic apparatus. From these
      transcriptional units, 146 are shared between the two strains, 42 are shared with
      the higher plant Arabidopsis thaliana and 25 with E. coli. To verify the
      existence of the respective MU-proteins in vivo, we selected five genes as
      examples to which a FLAG tag sequence was added and re-introduced them into
      Synechocystis sp. PCC 6803. These were the previously annotated gene ssr1169, two
      newly defined genes norf1 and norf4, as well as nsiR6 (nitrogen stress-induced
      RNA 6) and hliR1(high light-inducible RNA 1) , which originally were considered
      non-coding. Upon activation of expression via the Cu2+.responsive petE promoter
      or from the native promoters, all five proteins were detected in Western blot
      experiments. CONCLUSIONS: The distribution and conservation of these five genes
      as well as their regulation of expression and the physico-chemical properties of
      the encoded proteins underline the likely great bandwidth of small protein
      functions in bacteria and makes them attractive candidates for functional
      studies.

PMID- 27894277
TI  - Human limb skeletal muscle wasting and architectural remodeling during five to
      ten days intubation and ventilation in critical care - an observational study
      using ultrasound.
AB  - BACKGROUND: Critically ill patients frequently suffer muscle weakness whilst in
      critical care. Ultrasound can reliably track loss of muscle size, but also
      quantifies the arrangement of the muscle fascicles, known as the muscle
      architecture. We sought to measure both pennation angle and fascicle length, as
      well as tracking changes in muscle thickness in a population of critically ill
      patients. METHODS: On days 1, 5 and 10 after admission to critical care, muscle
      thickness was measured in ventilated critically ill patients using bedside
      ultrasound. Elbow flexor compartment, medial head of gastrocnemius and vastus
      lateralis muscle were investigated. In the lower limb, we determined the
      pennation angle to derive the fascicle length. RESULTS: We recruited and scanned
      22 patients on day 1 after admission to critical care, 16 were re-scanned on day
      5 and 9 on day 10. We found no changes to the size of the elbow flexor
      compartment over 10 days of admission. In the gastrocnemius, there were no
      significant changes to muscle thickness or pennation angle over 5 or 10 days. In
      the vastus lateralis, we found significant losses in both muscle thickness and
      pennation angle on day 5, but found that fascicle length is unchanged. Loss of
      muscle on day 5 was related to decreases in pennation angle. In both lower limb
      muscles, a positive relationship was observed between the pennation angle on day
      1, and the percentage of angle lost by days 5 and 10. DISCUSSION: Muscle loss in
      critically ill patients preferentially affects the lower limb, possibly due to
      the lower limb becoming prone to disuse atrophy. Muscle architecture of the thigh
      changes in the first 5 days of admission, in particular, we have demonstrated a
      correlation between muscle thickness and pennation angle. It is hypothesised that
      weakness in the lower limb occurs through loss of force generation via a reduced
      pennation angle. CONCLUSION: Using ultrasound, we have been able to demonstrate
      that muscle thickness and architecture of vastus lateralis undergo rapid changes
      during the early phase of admission to a critical care environment.

PMID- 27894278
TI  - Prevalence and factors associated with diabetes mellitus and impaired fasting
      glucose level among members of federal police commission residing in Addis Ababa,
      Ethiopia.
AB  - BACKGROUND: The prevalence of diabetes mellitus and factors associated with it,
      nowadays, are increasing in alarming rates among different occupational groups.
      Of these occupational groups are Police officers that, often, are exposed to
      unique life styles and stressful situations which may lead to diabetes mellitus
      and other cardiovascular diseases. Due to this reason, the present study was
      conducted to assess the prevalence and factors associated with diabetes mellitus
      and impaired fasting glucose level among members of federal police commission
      residing in Addis Ababa, Ethiopia. METHODS: A cross-sectional study design was
      conducted from April to May 2015. Multistage and systematic random sampling
      techniques were employed to select the study participants. The study population
      was federal police commission members living in Addis Ababa and served for at
      least a year. The data were collected using structured questionnaire, physical
      examinations and blood samples, based on the WHO stepwise approach. Data were
      entered in to SPSS version 20.0 and descriptive statistics and logistics
      regression were used for analysis. RESULTS: Out of the 1003 eligible subjects,
      936 (93.3%) police officers have participated in this study. The prevalence of
      overall impaired glucose homeostasis (IGH) was 120 (13%) of which 47 (5%) were
      diabetes and 73 (8%) were impaired fasting glucose. Whereas police rank, history
      of first degree relative who suffered from diabetes, hypertension and waist hip
      ratio showed a statistical significance with prevalence of diabetes mellitus,
      age, family history, hypertension, BMI and waist hip ratio were found to be
      associated with impaired fasting glucose. CONCLUSION: The study identified a high
      prevalence of IGH among the police officers. A priority should be given on
      preventive strategies of diabetes mellitus, as that of communicable diseases, by
      Federal Police Commission Health Service Directorate, Federal Ministry of Health
      and other concerned partners.

PMID- 27894279
TI  - Development of a community's self-efficacy scale for preventing social isolation
      among community-dwelling older people (Mimamori Scale).
AB  - BACKGROUND: Among older people in developed countries, social isolation leading
      to solitary death has become a public health issue of vital importance. Such
      isolation could be prevented by monitoring at-risk individuals at the
      neighborhood level and by implementing supportive networks at the community
      level. However, a means of measuring community confidence in these measures has
      not been established. This study is aimed at developing the Community's Self
      Efficacy Scale (CSES; Mimamori scale in Japanese) for community members
      preventing social isolation among older people. METHODS: The CSES is a self
      administered questionnaire developed on the basis of Bandura's self-efficacy
      theory. The survey was given to a general population (GEN) sample (n = 6,000) and
      community volunteer (CVOL) sample (n = 1,297). Construct validity was determined
      using confirmatory factor analysis. Internal consistency was calculated using
      Cronbach's alpha. The Generative Concern Scale (GCS-R) and Brief Sense of
      Community Scale (BSCS) were also administered to assess criterion-related
      validity of the CSES. RESULTS: In total, 3,484 and 859 valid responses were
      received in the GEN and CVOL groups, respectively. The confirmatory factor
      analysis identified eight items from two domains-community network and
      neighborhood watch-with goodness of fit index = 0.984, adjusted goodness of fit
      index = 0.970, comparative fit index = 0.988, and root mean square error of
      approximation = 0.047. Cronbach's alpha for the entire CSES was 0.87 and for the
      subscales was 0.80 and higher. The score of the entire CSES was positively
      correlated with the GCS-R in both the GEN (r = 0.80, p < 0.001) and CVOL (r =
      0.86, p < 0.001) samples. CONCLUSIONS: The CSES demonstrated adequate reliability
      and validity for assessing a community's self-efficacy to aid in its preventing
      social isolation among older people. The scale is potentially useful for
      promoting health policies, practices, and interventions within communities. This
      may help prevent social isolation among older people and contribute to overall
      well-being in aging societies in Japan and abroad.

PMID- 27894280
TI  - Is there any association between Sarcoidosis and infectious agents?: a systematic
      review and meta-analysis.
AB  - BACKGROUND: During the last few years, investigators have debated the role that
      infectious agents may have in sarcoidosis pathogenesis. With the emergence of new
      molecular biology techniques, several studies have been conducted; therefore, we
      performed a meta-analysis in order to better explain this possible association.
      METHODS: This review was conducted in accordance with the Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) statement from the
      Cochrane collaboration guidelines. Four different databases (Medline, Scopus, Web
      of Science, and Cochrane Collaboration) were searched for all original articles
      published from 1980 to 2015. The present meta-analysis included case-control
      studies that reported the presence of microorganisms in samples of patients with
      sarcoidosis using culture methods or molecular biology techniques. We used a
      random effects or a fixed-effect model to calculate the odds ratio (OR) and 95%
      confidence intervals (CI). Sensitivity and subgroup analyses were performed in
      order to explore the heterogeneity among studies. RESULTS: Fifty-eight studies
      qualified for the purpose of this analysis. The present meta-analysis, the first,
      to our knowledge, in evaluation of all infectious agents proposed to be
      associated with sarcoidosis and involving more than 6000 patients in several
      countries, suggests an etiological link between Propionibacterium acnes and
      sarcoidosis, with an OR of 18.80 (95% CI 12.62, 28.01). We also found a
      significant association between sarcoidosis and mycobacteria, with an OR of 6.8
      (95% CI 3.73, 12.39). Borrelia (OR 4.82; 95% CI 0.98, 23.81), HHV-8 (OR 1.47; 95%
      CI 0.02, 110.06) as well as Rickettsia helvetica, Chlamydia pneumoniae, Epstein
      barr virus and Retrovirus, although suggested by previous investigations, were
      not associated with sarcoidosis. CONCLUSION: This meta-analysis suggests that
      some infectious agents can be associated with sarcoidosis. What seems clear is
      that more than one infectious agent might be implicated in the pathogenesis of
      sarcoidosis; probably the patient's geographical location might dictate which
      microorganisms are more involved. Future investigations and more clinical trials
      are need to bring these evidences to a more global level.

PMID- 27894281
TI  - Successful selective reduction of a heterotopic cesarean scar pregnancy in the
      second trimester: a case report and review of the literature.
AB  - BACKGROUND: Heterotopic cesarean scar pregnancy is a cesarean scar pregnancy
      combined with an intrauterine pregnancy that predisposes a woman to life
      threatening complications such as uterine rupture and massive bleeding.
      Preservation of the intrauterine pregnancy in heterotopic cesarean scar pregnancy
      is a great challenge. CASE PRESENTATION: We report a case of a 33-year-old woman
      with heterotopic cesarean scar pregnancy after IVF-embryo transfer (ET).
      Expectant management was carried out with early diagnosis of heterotopic cesarean
      scar pregnancy (HCSP), and selective fetal reduction of cesarean scar pregnancy
      (CSP) was performed by ultrasound-guided intrathoracic injection of potassium
      chloride (KCl) at 16 + 4 weeks of gestation due to aggravation of CSP.
      Preservation of the intrauterine pregnancy was successful and a healthy baby was
      delivered by cesarean section at 37 + 6 weeks of gestation. CONCLUSIONS:
      Heterotopic cesarean scar pregnancy is an extremely rare form of heterotopic
      pregnancy. Patients should be appropriately counseled regarding the different
      treatment options available. An ultrasound-guided injection of potassium chloride
      may constitute a safe, minimally invasive and reliable way to terminate the
      heterotopic gestation and preserve the intrauterine pregnancy. Intensive
      management should be performed during the ongoing pregnancy and cesarean section.

PMID- 27894282
TI  - Health-related quality of life in stroke patients questionnaire, short version
      (HRQOLISP-40): validation for its use in Colombia.
AB  - BACKGROUND: The health-related quality of life in stroke patients (HRQOLISP-40,
      short version) survey was developed in Nigeria and constitutes a 40-item,
      multidimensional, self-administrated questionnaire. We assessed the validity and
      reliability of the HRQOLISP-40 Spanish version for stroke patients in Colombia.
      METHODS: The analysis included factor analysis, confirmatory factor analysis,
      Rasch analysis, convergent validity, internal consistency (261 stroke patients),
      test-retest reliability (73 patients assessed at two different times) and
      sensitivity to change (46 patients assessed before and after a rehabilitation
      intervention). RESULTS: We found an 8-domain structure. None of the items had a
      significant impact on the global alpha value in order to be removed. Lin's
      concordance correlation coefficient indicated test-retest reliability (Rho IC:
      0.76 to 0.95), suggesting an adequate stability of the instrument. Regarding
      sensitivity to change differences, they were only significant in the
      psychological and eco-social domains (p <0.05). When comparing SF-36 with
      HRQOLISP-40, all the correlation coefficients values were significantly different
      from zero, except those related to vitality. The highest scores were found in the
      physical and physical functioning domains, with a value of 0.722. CONCLUSIONS:
      The HRQOLISP-40 scale is valid and reliable for assessing patients' quality of
      life after a stroke. Validating quality of life assessment instruments is
      necessary in order to improve the effectiveness of rehabilitation programs for
      Colombian stroke patients.

PMID- 27894283
TI  - Small lung lesions invisible under fluoroscopy are located accurately by three
      dimensional localization technique on chest wall surface and performed
      bronchoscopy procedures to increase diagnostic yields.
AB  - BACKGROUND: Nowadays, small peripheral pulmonary lesions (PPLs) are frequently
      detected and the prognosis of lung cancer depends on the early diagnosis. Because
      of the high fee and requiring specialized training, many advanced techniques are
      not available in many developing countries and rural districts. METHODS: Three
      sets of opaque soft copper wires visible under the fluoroscopy (Flu) in the Flu
      flexible bronchoscopy (FB) group (n = 24), which determined the three planes of
      the lesion, were respectively placed firmly on the surface of the chest wall with
      adhesive tape on the chest wall. The FB tip was advanced into the bronchus toward
      the crosspoint of the three perpendicular planes under Flu with careful rotation
      of a C-arm unit. Then the specimen were harvested focusing around the crosspoint
      for pathologic diagnosis. The rapid on-site evaluation (ROSE) procedure was also
      performed. The average Flu time during FB procedures were recorded and diagnostic
      accuracy rates in the Flu-FB group were compared with the other group guided by
      radial endobronchial ultrasound (R-EBUS) (n = 23). RESULTS: The location of the
      core point of the lesion, whether it was visible or not under the fluoroscopy
      could be recognized by three-dimensional localization technique. The accuracy
      rates of diagnostic yields were 62.5% in the Flu-FB group, and was similar as
      65.2% in the R-EBUS group (P > 0.05). However, in the Flu-FB group, there was a
      decreasing tendency on accurate diagnosis rates of lower lobe (LL) lesions when
      comparing with non-LL lesions (3/8 = 37.5% vs 12/16 = 75%, P = 0.091) while in
      the R-EBUS group it was similar (9/12 = 75% vs 6/11 = 54.6%, P = 0.278). In the
      Flu-FB group, fluoroscopy time was negatively correlated with the lesion length
      (r = -0.613, P = 0.001), however, there was no significant difference between the
      lesions invisible or not (5.83 +/- 1.45 min vs 7.67 +/- 2.02 min, P = 0.116)
      under the fluoroscopy, as well as no significant difference among SPN, mGGO and
      GGO (6.12 +/- 2.05 min, 7.25 +/- 1.33 min and 7.80 +/- 2.02 min, P > 0.05).
      CONCLUSIONS: Small PPL whether it is visible or not under fluoroscopy can be
      located accurately by our three-dimensional localization technique on chest wall
      surface and performed bronchoscopy procedures to increase diagnostic yields. It
      is more convenient, economical and reliable with the similar diagnostic yields
      than R-EBUS guided method. TRIAL REGISTRATION: Current Controlled Trials ChiCTR
      DDD-16009715 . The date of registration: 3rd Nov, 2016. Retrospectively
      registered.

PMID- 27894285
TI  - Implementing an electronic learning management system for an Ophthalmology
      residency program.
AB  - BACKGROUND: Medical educators, residents and administrators have increasing
      access to a large quantity of electronic resources. This content can augment and
      improve our teaching methods but can be difficult to consolidate and present. A
      multitude of electronic learning management systems are available to help
      organize and serve this content though never with small residency programs as the
      target userbase. As our residency program in Ophthalmology looked to consolidate
      our electronic resources and update our education methods, we evaluated and built
      an electronic learning management platform. RESULTS: Faculty were interviewed to
      determine features they would find useful in curriculum management system and
      then various systems were investigated for features, cost and ease of use.
      CONCLUSIONS: Our solution has been both cost-effective and successful. Resident
      satisfaction is high and faculty utilization has been increasing. We present many
      customizations that increased success. Consideration of the specific needs of a
      program is paramount to choosing a cost effective solution that will be well
      received.

PMID- 27894284
TI  - Proarrhythmic risk and determinants of cardiac autonomic dysfunction in collagen
      induced arthritis rats.
AB  - BACKGROUNDS: Patients with rheumatoid arthritis (RA) have increased risk of
      sudden cardiac death (SCD), which is two-fold higher than general population. The
      driving cause of SCD was considered due to lift-threatening arrhythmia where
      systemic inflammation acts as the pathophysiological basis linking RA to
      autonomicdysfunction. METHODS: To assess the sympathetic over-activity of
      "inflammatory reflex", we measured heart rate variability (HRV) in a rat collagen
      induced arthritis (CIA) model, whose arthritis is induced in Lewis rats by
      intradermal injection of emulsion of type II collagen. Single-lead
      electrocardiogram (ECG) was recorded for 30 min every two days. Time and
      frequency-domain parameters, detrended fluctuation analysis (DFA), deceleration
      (DC) and acceleration capacity (AC) were analyzed. RESULTS: Compared with 9
      control rats, many of HRV parameters of 9 CIA rats revealed significant
      different. At the beginning of arthritis, LF/HF was significant higher than
      controls (1st week: 2.41 +/- 0.7 vs. 1.76 +/- 0.6, p < 0.05; 2nd week: 2.24 +/-
      0.5 vs. 1.58 +/- 0.5, p < 0.05) indicating intensive inflammatory reflex at the
      initial phase of inflammation but no significant difference was observed in the
      following recover phase. The similar trend of DFA parameters was noted. However,
      the DC appeared progressive lower despite of no significant increase of the LF/HF
      compared with controls since 4th week. CONCLUSIONS: We observed sympathetic over
      activation of inflammatory reflex during early stage of arthritis in CIA rats.
      The ongoing decline of DC indicated advanced cardiac autonomic dysfunction
      regardless of remission of acute arthritis.

PMID- 27894286
TI  - The family experiences of in-hospital care questionnaire in severe traumatic
      brain injury (FECQ-TBI): a validation study.
AB  - BACKGROUND: Family members are important for support and care of their close
      relative after severe traumas, and their experiences are vital health care
      quality indicators. The objective was to describe the development of the Family
      Experiences of in-hospital Care Questionnaire for family members of patients with
      severe Traumatic Brain Injury (FECQ-TBI), and to evaluate its psychometric
      properties and validity. METHODS: The design of the study is a Norwegian
      multicentre study inviting 171 family members. The questionnaire developmental
      process included a literature review, use of an existing instrument (the parent
      experience of paediatric care questionnaire), focus group with close family
      members, as well as expert group judgments. Items asking for family care
      experiences related to acute wards and rehabilitation were included. Several
      items of the paediatric care questionnaire were removed or the wording of the
      items was changed to comply with the present purpose. Questions covering
      experiences with the inpatient rehabilitation period, the discharge phase, the
      family experiences with hospital facilities, the transfer between departments and
      the economic needs of the family were added. The developed questionnaire was
      mailed to the participants. Exploratory factor analyses were used to examine
      scale structure, in addition to screening for data quality, and analyses of
      internal consistency and validity. RESULTS: The questionnaire was returned by 122
      (71%) of family members. Principal component analysis extracted six dimensions
      (eigenvalues > 1.0): acute organization and information (10 items),
      rehabilitation organization (13 items), rehabilitation information (6 items),
      discharge (4 items), hospital facilities-patients (4 items) and hospital
      facilities-family (2 items). Items related to the acute phase were comparable to
      items in the two dimensions of rehabilitation: organization and information. All
      six subscales had high Cronbach's alpha coefficients >0.80. The construct
      validity was confirmed. CONCLUSION: The FECQ-TBI assesses important aspects of in
      hospital care in the acute and rehabilitation phases, as seen from a family
      perspective. The psychometric properties and the construct validity of the
      questionnaire were good, hence supporting the use of the FECQ-TBI to assess
      quality of care in rehabilitation departments.

PMID- 27894287
TI  - Towards a preventive strategy for complaints of arm, neck and/or shoulder (CANS):
      the role of help seeking behaviour.
AB  - BACKGROUND: When developing an effective early preventive strategy for employees
      and students with CANS (Complaints of Arm, Neck or Shoulder, not caused by acute
      trauma or systemic disease), insight in help seeking behaviour and knowledge of
      factors associated with help seeking behaviour within the target population, is a
      prerequisite. The aim of this study was to examine whether perceived hindrance is
      associated with help seeking behaviour, specifically in employees and students
      identified with CANS. Additionally, the associations of factors related to
      functioning and participation, work-environment and demographics with help
      seeking behaviour were explored in these groups. METHODS: A cross-sectional
      survey was conducted among employees and students of two universities in the
      South of the Netherlands. The questionnaire included questions to assess (1)
      demographics, work/study and activity related factors (2) experience of CANS (3)
      perceived hindrance (4) help seeking behaviour. A subpopulation of the survey,
      consisting of those employees and students with self-reported CANS, received
      additional questionnaires to examine the impact of (1) participant
      characteristics (2) complaint and health related variables (3) functioning and
      participation (4) work-environment and social support, on help seeking behaviour.
      RESULTS: 37.3% of the employees and 41.4% of the students reported CANS. Of
      these, respectively 43.3% and 45.5%, did not seek help and had no intention to
      seek help either. Employees and students who had not sought help reported less
      hindrance, less perceived disabilities and shorter duration of complaints,
      compared those who did seek help. Employees and students within this group who
      had also no intention to seek help, perceived fewer disabilities and reported
      shorter duration of complaints. CONCLUSION: The absence of help seeking behaviour
      in respondents with CANS is a bottleneck for implementation of preventive
      strategies. In employees and students with CANS, help seeking behaviour is
      primarily determined by factors related to experienced hindrance. Our findings
      emphasize the need to tailor preventive strategies, in order to optimize
      screening and participation in early interventions for CANS.

PMID- 27894288
TI  - Bactericidal and antioxidant properties of essential oils from the fruits
      Dennettia tripetala G. Baker.
AB  - BACKGROUND: The antibacterial and antioxidant properties of the essential oils
      (EOs) of unripe and ripe fruits of Dennettia tripetala and their potential for
      the management of infectious and oxidative-stress diseases were investigated in
      vitro in this study. METHOD: Essential oil obtained from the fruit in Clevenger
      modified apparatus, was characterized by high resolution GC-MS, while antioxidant
      and antibacterial properties were tested by spectrophotometric and agar diffusion
      methods respectively. RESULTS: The EO demonstrated strong antibacterial
      properties when subjected to multi -drug resistant bacterial strains:
      Enterococcus faecium (ATCC19434), Escherichia coli (ATCC 700728), Staphylococcus
      aureus (NCINB 50080), Listeria ivanovii (ATCC 19119), Enterobacter cloacae
      (ATCC13047) and four previously confirmed multi resistant bacterial isolates from
      our laboratory stock culture. The unripe fruit oil (UFO) demonstrated greater
      activity than the ripe fruit oil (RFO) against most of the tested bacteria with
      minimum inhibition concentrations (MIC) ranging between 0.05-0.20 mg/mL while
      that of the ripe fruit oil (RFO) ranged from 0.10-0.20 mg/mL. The IC50 for RFO
      (0.62 +/- 0.12 mg/mL) showed that it has higher antioxidant strength than UFO and
      vitamin C (0.87 +/- 0.23 and 3.39 +/- 0.12 mg/mL) but a lower activity compared
      to beta-carotene (0.32 +/- 0.22 mg/mL) in scavenging 2, 2-diphenyl-1
      picrylhydrazyl radicals (DPPH*). The EOs also demonstrated strong ability in
      scavenging three other different radicals (ABTS, lipid peroxide and nitric oxide
      radicals) in concentration dependant -manner. CONCLUSION: Findings from this
      study suggest that apart from the local uses of the plant extracts, the EO has
      strong bioactive compounds, noteworthy antibacterial, antiradical properties and
      may be good candidates in the search for lead constituents for the synthesis of
      novel potent antibiotics.

PMID- 27894289
TI  - The patient reporting and action for a safe environment (PRASE) intervention: a
      feasibility study.
AB  - BACKGROUND: There is growing interest in the role of patients in improving
      patient safety. One such role is providing feedback on the safety of their care.
      Here we describe the development and feasibility testing of an intervention that
      collects patient feedback on patient safety, brings together staff to consider
      this feedback and to plan improvement strategies. We address two research
      questions: i) to explore the feasibility of the process of systematically
      collecting feedback from patients about the safety of care as part of the PRASE
      intervention; and, ii) to explore the feasibility and acceptability of the PRASE
      intervention for staff, and to understand more about how staff use the patient
      feedback for service improvement. METHOD: We conducted a feasibility study using
      a wait-list controlled design across six wards within an acute teaching hospital.
      Intervention wards were asked to participate in two cycles of the PRASE (Patient
      Reporting & Action for a Safe Environment) intervention across a six-month
      period. Participants were patients on participating wards. To explore the
      acceptability of the intervention for staff, observations of action planning
      meetings, interviews with a lead person for the intervention on each ward and
      recorded researcher reflections were analysed thematically and synthesised.
      RESULTS: Recruitment of patients using computer tablets at their bedside was
      straightforward, with the majority of patients willing and able to provide
      feedback. Randomisation of the intervention was acceptable to staff, with no
      evidence of differential response rates between intervention and control groups.
      In general, ward staff were positive about the use of patient feedback for
      service improvement and were able to use the feedback as a basis for action
      planning, although engagement with the process was variable. Gathering a
      multidisciplinary team together for action planning was found to be challenging,
      and implementing action plans was sometimes hindered by the need to co-ordinate
      action across multiple services. DISCUSSION: The PRASE intervention was found to
      be acceptable to staff and patients. However, before proceeding to a full cluster
      randomised controlled trial, the intervention requires adaptation to account for
      the difficulties in implementing action plans within three months, the need for a
      facilitator to support the action planning meetings, and the provision of
      training and senior management support for participating ward teams. CONCLUSIONS:
      The PRASE intervention represents a promising method for the systematic
      collection of patient feedback about the safety of hospital care.

PMID- 27894290
TI  - Erratum to: APC selectively mediates response to chemotherapeutic agents in
      breast cancer.

PMID- 27894291
TI  - HPV Prevalence in the Dutch cervical cancer screening population (DuSC study):
      HPV testing using automated HC2, cobas and Aptima workflows.
AB  - BACKGROUND: Primary high risk (hr)HPV screening will be introduced in The
      Netherlands in January 2017. Our aim was to determine the hrHPV prevalence in the
      Dutch cervical cancer screening population (DuSC study). METHODS: A total of
      12,113 residual PreservCyt cervical samples from the Dutch population based
      cytology screening program were rendered anonymous, randomized and tested for
      hrHPV using 3 HPV assays on their respective automated platforms: QIAGEN's
      digene(r) HC2 HPV DNA Test(r) (HC2, signal amplification), Roche Cobas(r) HPV
      test (DNA amplification) and Hologic Aptima(r) HPV Test (RNA amplification). To
      determine the agreement between results generated using the different assays,
      pair wise comparison of the systems was performed by determining kappa
      coefficients. RESULTS: The selected samples were representative for the
      population based screening program with respect to age distribution and cytology
      classification. HrHPV prevalences found were: 8.5% for HC2 (n = 959), 8.1% for
      cobas (n = 919) and 7.5% for Aptima (n = 849), resulting in a mean hrHPV
      prevalence of 8.0 +/- 0.5%. Although the hrHPV prevalences of the different
      assays are in the range of 8%, there was a significant difference in prevalence
      for the HC2 vs. Aptima assay (p-value = 0.007). A clear age dependency was found,
      with an hrHPV prevalence ranging from 18.7 +/- 1.2% in women 29-33 years of age
      to 4.2 +/- 0.2% in women 59-63 years of age. Furthermore, a correlation between
      hrHPV prevalence and severity of cytology was observed, ranging from 5.5 +/- 0.4%
      in normal cytology to 95.2 +/- 1.7% in severe dysplasia. Indeed, kappa
      coefficients of 0.77, 0.71 and 0.72 (HC2 vs cobas, cobas vs Aptima and Aptima vs
      HC2, respectively) indicated substantial agreement between the results generated
      by the different systems. However, looking at the hrHPV positive samples, only
      48% of the samples tested positive with all 3 assays. CONCLUSIONS: A hrHPV
      prevalence of 8% was found in this unselected population based screening cohort
      independently of using HC2, Aptima or cobas. This prevalence is higher than the
      previously reported 4-5% (POBASCAM and VUSA-Screen trials). Furthermore, the
      complete automated hrHPV detection workflow solutions from QIAGEN, Roche, and
      Hologic were successfully used and will be valuable for reliably implementing
      high throughput hrHPV testing in cervical cancer screening.

PMID- 27894292
TI  - Reliability of breath by breath spirometry and relative flow-time indices for
      pulmonary function testing in horses.
AB  - BACKGROUND: Respiratory problems are common in horses, and are often diagnosed as
      a cause of poor athletic performance. Reliable, accurate and sensitive
      spirometric tests of airway function in resting horses would assist with the
      diagnosis of limitations to breathing and facilitate investigations of the
      effects of various treatments on breathing capacity. The evaluation of
      respiratory function in horses is challenging and suitable procedures are not
      widely available to equine practitioners. The determination of relative flow or
      flow-time measures is used in paediatric patients where compliance may limit
      conventional pulmonary function techniques. The aim of the current study was to
      characterise absolute and relative indices of respiratory function in healthy
      horses during eupnoea (tidal breathing) and carbon dioxide (CO2)-induced
      hyperpnoea (rebreathing) using a modified mask pneumotrachographic technique well
      suited to equine practice, and to evaluate the reliability of this technique over
      three consecutive days. Coefficients of variation, intra-class correlations, mean
      differences and 95% confidence intervals across all days of testing were
      established for each parameter. RESULTS: The technique provided absolute measures
      of respiratory function (respiratory rate, tidal volume, peak inspiratory and
      expiratory flows, time to peak flow) consistent with previous studies and there
      was no significant effect of day on any measure of respiratory function.
      Variability of measurements was decreased during hyperpnea caused by rebreathing
      CO2, but a number of relative flow-time variables demonstrated good agreement
      during eupnoeic respiration. CONCLUSIONS: The technique was well tolerated by
      horses and study findings suggest the technique is suitable for evaluation of
      respiratory function in horses. The use of relative flow-time variables provided
      reproducible (consistent) results, suggesting the technique may be of use for
      repeated measures studies in horses during tidal breathing or rebreathing.

PMID- 27894294
TI  - Appropriate threshold levels of cardiac beat-to-beat variation in semi-automatic
      analysis of equine ECG recordings.
AB  - BACKGROUND: Although premature beats are a matter of concern in horses, the
      interpretation of equine ECG recordings is complicated by a lack of standardized
      analysis criteria and a limited knowledge of the normal beat-to-beat variation of
      equine cardiac rhythm. The purpose of this study was to determine the appropriate
      threshold levels of maximum acceptable deviation of RR intervals in equine ECG
      analysis, and to evaluate a novel two-step timing algorithm by quantifying the
      frequency of arrhythmias in a cohort of healthy adult endurance horses. RESULTS:
      Beat-to-beat variation differed considerably with heart rate (HR), and an
      adaptable model consisting of three different HR ranges with separate threshold
      levels of maximum acceptable RR deviation was consequently defined. For resting
      HRs <60 beats/min (bpm) the threshold level of RR deviation was set at 20%, for
      HRs in the intermediate range between 60 and 100 bpm the threshold was 10%, and
      for exercising HRs >100 bpm, the threshold level was 4%. Supraventricular
      premature beats represented the most prevalent arrhythmia category with varying
      frequencies in seven horses at rest (median 7, range 2-86) and six horses during
      exercise (median 2, range 1-24). CONCLUSIONS: Beat-to-beat variation of equine
      cardiac rhythm varies according to HR, and threshold levels in equine ECG
      analysis should be adjusted accordingly. Standardization of the analysis criteria
      will enable comparisons of studies and follow-up examinations of patients. A
      small number of supraventricular premature beats appears to be a normal finding
      in endurance horses. Further studies are required to validate the findings and
      determine the clinical significance of premature beats in horses.

PMID- 27894293
TI  - Lung bioengineering: physical stimuli and stem/progenitor cell biology interplay
      towards biofabricating a functional organ.
AB  - A current approach to obtain bioengineered lungs as a future alternative for
      transplantation is based on seeding stem cells on decellularized lung scaffolds.
      A fundamental question to be solved in this approach is how to drive stem cell
      differentiation onto the different lung cell phenotypes. Whereas the use of
      soluble factors as agents to modulate the fate of stem cells was established from
      an early stage of the research with this type of cells, it took longer to
      recognize that the physical microenvironment locally sensed by stem cells (e.g.
      substrate stiffness, 3D architecture, cyclic stretch, shear stress, air-liquid
      interface, oxygenation gradient) also contributes to their differentiation. The
      potential role played by physical stimuli would be particularly relevant in lung
      bioengineering since cells within the organ are physiologically subjected to two
      main stimuli required to facilitate efficient gas exchange: air ventilation and
      blood perfusion across the organ. The present review focuses on describing how
      the cell mechanical microenvironment can modulate stem cell differentiation and
      how these stimuli could be incorporated into lung bioreactors for optimizing
      organ bioengineering.

PMID- 27894295
TI  - Impact of a web-based tool (WebCONSORT) to improve the reporting of randomised
      trials: results of a randomised controlled trial.
AB  - BACKGROUND: The CONSORT Statement is an evidence-informed guideline for reporting
      randomised controlled trials. A number of extensions have been developed that
      specify additional information to report for more complex trials. The aim of this
      study was to evaluate the impact of using a simple web-based tool (WebCONSORT,
      which incorporates a number of different CONSORT extensions) on the completeness
      of reporting of randomised trials published in biomedical publications. METHODS:
      We conducted a parallel group randomised trial. Journals which endorsed the
      CONSORT Statement (i.e. referred to it in the Instruction to Authors) but do not
      actively implement it (i.e. require authors to submit a completed CONSORT
      checklist) were invited to participate. Authors of randomised trials were
      requested by the editor to use the web-based tool at the manuscript revision
      stage. Authors registering to use the tool were randomised (centralised computer
      generated) to WebCONSORT or control. In the WebCONSORT group, they had access to
      a tool allowing them to combine the different CONSORT extensions relevant to
      their trial and generate a customised checklist and flow diagram that they must
      submit to the editor. In the control group, authors had only access to a CONSORT
      flow diagram generator. Authors, journal editors, and outcome assessors were
      blinded to the allocation. The primary outcome was the proportion of CONSORT
      items (main and extensions) reported in each article post revision. RESULTS: A
      total of 46 journals actively recruited authors into the trial (25 March 2013 to
      22 September 2015); 324 author manuscripts were randomised (WebCONSORT n = 166;
      control n = 158), of which 197 were reports of randomised trials (n = 94; n =
      103). Over a third (39%; n = 127) of registered manuscripts were excluded from
      the analysis, mainly because the reported study was not a randomised trial. Of
      those included in the analysis, the most common CONSORT extensions selected were
      non-pharmacologic (n = 43; n = 50), pragmatic (n = 20; n = 16) and cluster (n =
      10; n = 9). In a quarter of manuscripts, authors either wrongly selected an
      extension or failed to select the right extension when registering their
      manuscript on the WebCONSORT study site. Overall, there was no important
      difference in the overall mean score between WebCONSORT (mean score 0.51) and
      control (0.47) in the proportion of CONSORT and CONSORT extension items reported
      pertaining to a given study (mean difference, 0.04; 95% CI -0.02 to 0.10).
      CONCLUSIONS: This study failed to show a beneficial effect of a customised web
      based CONSORT checklist to help authors prepare more complete trial reports.
      However, the exclusion of a large number of inappropriately registered
      manuscripts meant we had less precision than anticipated to detect a difference.
      Better education is needed, earlier in the publication process, for both authors
      and journal editorial staff on when and how to implement CONSORT and, in
      particular, CONSORT-related extensions. TRIAL REGISTRATION: ClinicalTrials.gov:
      NCT01891448 [registered 24 May 2013].

PMID- 27894296
TI  - Relationship between body mass index and depressive symptoms: the "fat and jolly"
      hypothesis for the middle-aged and elderly in China.
AB  - BACKGROUND: Obesity has been identified as a worldwide epidemic. In China, the
      highest prevalence of obesity is observed in adults aged >=45 years old. This
      study aimed to describe the association between BMI and depressive symptoms among
      a large representative sample of middle-aged and elderly in China. METHOD: A
      longitudinal sample of the middle-aged and elderly (6,224 males and 6,883
      females) who were interviewed in the 2011 China Health and Retirement
      Longitudinal Study was used. A multivariate logistic regression analysis was used
      to examine the effects of socio-demographic characteristics, lifestyle, activity
      status, health status, physical exercise and body weight on depressive symptoms.
      RESULTS: Approximately 6.94% of the males were underweight, 25.48% were
      overweight and 8.16% were obese. A higher prevalence of obesity was found among
      women, with 6.89% being underweight, 31.98% overweight and 14.28% obese. The
      underweight subjects were more likely to be depressed (odds ratio; OR = 1.30 and
      1.19) compared with the normal weight people, respectively, whereas overweight
      and obese men and women were less likely to be depressed (overweight: OR = 0.76
      and 0.80; obesity: OR = 0.64 and 0.65, respectively) than people of normal
      weight. CONCLUSION: Our data are consistent with the "fat and jolly" hypothesis
      being valid in both middle-aged and elderly men and women.

PMID- 27894297
TI  - Pulmonary hypertension and vascular remodeling in mice exposed to crystalline
      silica.
AB  - BACKGROUND: Occupational and environmental exposure to crystalline silica may
      lead to the development of silicosis, which is characterized by inflammation and
      progressive fibrosis. A substantial number of patients diagnosed with silicosis
      develop pulmonary hypertension. Pulmonary hypertension associated with silicosis
      and with related restrictive lung diseases significantly reduces survival in
      affected subjects. An animal model of silicosis has been described previously
      however, the magnitude of vascular remodeling and hemodynamic effects of inhaled
      silica are largely unknown. Considering the importance of such information, this
      study investigated whether mice exposed to silica develop pulmonary hypertension
      and vascular remodeling. METHODS: C57BL6 mice were intratracheally injected with
      either saline or crystalline silica at doses 0.2 g/kg, 0.3 g/kg and 0.4 g/kg and
      then studied at day 28 post-exposure. Pulmonary hypertension was characterized by
      changes in right ventricular systolic pressure and lung histopathology. RESULTS:
      Mice exposed to saline showed normal lung histology and hemodynamic parameters
      while mice exposed to silica showed increased right ventricular systolic pressure
      and marked lung pathology characterized by a granulomatous inflammatory reaction
      and increased collagen deposition. Silica-exposed mice also showed signs of
      vascular remodeling with pulmonary artery muscularization, vascular occlusion,
      and medial thickening. The expression of pro-inflammatory genes such as TNF-alpha
      and MCP-1 was significantly upregulated as well as the expression of the pro
      remodeling genes collagen type I, fibronectin and the metalloproteinases MMP-2
      and TIMP-1. On the other hand, the expression of several vasculature specific
      genes involved in the regulation of endothelial function was significantly
      attenuated. CONCLUSIONS: We characterized a new animal model of pulmonary
      hypertension secondary to pulmonary fibrosis induced by crystalline silica. Our
      data suggest that silica promotes the damage of the pulmonary vasculature through
      mechanisms that might involve endothelial dysfunction, inflammation, and vascular
      remodeling.

PMID- 27894299
TI  - Evolutionary phylodynamics of foot-and-mouth disease virus serotypes O and A
      circulating in Vietnam.
AB  - BACKGROUND: Foot-and-mouth disease virus (FMDV) is one of the highest risk
      factors that affects the animal industry of the country. The virus causes
      production loss and high ratio mortality in young cloven-hoofed animals in
      Vietnam. The VP1 coding gene of 80 FMDV samples (66 samples of the serotype O and
      14 samples of the serotype A) collected from endemic outbreaks during 2006-2014
      were analyzed to investigate their phylogeny and genetic relationship with other
      available FMDVs globally. RESULTS: Phylogenetic analysis indicated that the
      serotype O strains were clustered into two distinct viral topotypes (the SEA and
      ME-SA), while the serotype A strains were all clustered into the genotype IX.
      Among the study strains, the amino acid sequence identities were shared at a
      level of 90.1-100, 92.9-100, and 92.8-100% for the topotypes SEA, ME-SA, and
      genotype IX, respectively. Substitutions leading to changes in the amino acid
      sequence, which are critical for the VP1 antigenic sites were also identified.
      Our results showed that the studied strains are most closely related to the
      recent FMDV isolates from Southeast Asian countries (Myanmar, Thailand, Cambodia,
      Malaysia, and Laos), but are distinct from the earlier FMDV isolates within the
      genotypes. CONCLUSIONS: This study provides important evidence of recent movement
      of FMDVs serotype O and A into Vietnam within the last decade and their genetic
      accumulation to be closely related to strains causing FMD in surrounding
      countries.

PMID- 27894301
TI  - Erratum to: Advanced Practice Pharmacists: a retrospective evaluation of the
      efficacy and cost of ClinicaL Pharmacist PractitionErs managing ambulatory
      Medicare patients in North Carolina (APPLE-NC).

PMID- 27894298
TI  - Effect of continuity of care on health-related quality of life in adult patients
      with hypertension: a cohort study in China.
AB  - BACKGROUND: Continuity of care is widely considered a principle of primary care
      that decreases healthcare utilization and mortality. However, the effect of
      continuity of care on health-related quality of life (HRQoL) for adult patients
      with hypertension remains unclear. METHODS: To further evaluate the effect of
      continuity of care, we implemented a cohort study among hypertensive patients
      aged over 35 years (n = 1200) in six townships in Qianjiang District, Chongqing,
      China, between 2012 and 2014. The study ultimately included 1079 participants.
      The continuity of care index was calculated using claim-based longitudinal data
      obtained from hypertension follow-up service records. The baseline and endline
      survey-based data, tested by the SF-36 scale, were used to assess HRQoL. To
      control selection bias and examine the effect of continuity of care, a kernel
      based propensity score matching difference-in-differences (DID) method was used.
      Additionally, descriptive statistics, chi-squared test, and Mann-Whitney
      nonparametric test were used to summarize characteristics, evaluate proportional
      differences, and analyze statistical differences, respectively. RESULTS: Our
      results showed that patients in the high continuity of care group presented
      greater improvement in both Physical Component Summary (PCS, DID = 5.192 +/-
      1.970, p < 0.001) and Mental Component Summary (MCS, DID = 7.900 +/- 1.815, p =
      0.008) than those in the low continuity of care group. Moreover, patients in the
      high continuity of care group showed significant improvement in physical
      functioning, role-physical, general health, role-emotional, and mental health.
      CONCLUSIONS: Our findings indicate that a long-term physician-patient
      relationship may improve HRQoL in patients with hypertension. However, more
      unified measurement tools are needed to evaluate continuity of care. Further
      studies should include more study settings.

PMID- 27894300
TI  - Pleural inhibition of the caspase-1/IL-1beta pathway diminishes profibrotic lung
      toxicity of bleomycin.
AB  - BACKGROUND: Idiopathic and toxic pulmonary fibrosis are severe diseases starting
      classically in the subpleural area of the lung. It has recently been suggested
      that pleural mesothelial cells acquire a myofibroblast phenotype under fibrotic
      conditions induced by TGF-beta1 or bleomycin. The importance and role of
      inflammation in fibrogenesis are still controversial. In this work, we explored
      the role of IL-1beta/caspase-1 signaling in bleomycin lung toxicity and in
      pleural mesothelial cell transformation. METHODS: C57BL/6 mice were intravenously
      injected with either bleomycin or nigericin or NaCl as control. In vitro, the
      Met5A cell line was used as a model of human pleural mesothelial cells. RESULTS:
      Intravenous injections of bleomycin induced lung fibrosis with histologically
      proven peripheral distribution, collagen accumulation in the pleural and
      subpleural area, and overexpression of markers of myofibroblast transformation of
      pleural cells which migrated into the lung. These events were associated with an
      inflammatory process with an increase in neutrophil recruitment in pleural lavage
      fluid and increased caspase-1 activity. TGF-beta1 was also overexpressed in
      pleural lavage fluid and was produced by pleural cells following intravenous
      bleomycin. In this model, local pleural inhibition of IL-1beta with the IL-1beta
      inhibitor anakinra diminished TGF-beta1 and collagen accumulation. In vitro,
      caspase-1 inhibition interfered with Met5A cell transformation into the
      myofibroblast-like phenotype induced by bleomycin or TGF-beta1. Moreover,
      nigericin, a caspase-1 activator, triggered transformation of Met5A cells and its
      intra-pleural delivery induced fibrogenesis in mice. CONCLUSIONS: We
      demonstrated, after intravenous bleomycin injection in mice, the role of the
      pleura and highlighted the key role of IL-1beta/caspase-1 axis in this
      fibrogenesis process.

PMID- 27894302
TI  - Anti-inflammatory and burn injury wound healing properties of the shell of
      Haliotis diversicolor.
AB  - BACKGROUND: The shell of Haliotis diversicolor, or shijueming (SJM), is a type of
      traditional Chinese medicine. The SJM has appeared in historical records as early
      as the third and fourth centuries. Historical records have revealed that SJM had
      mainly been used to treat eye diseases. After the Qing Dynasty (1757), records
      had emerged, detailing the use of SJM for treating skin injuries, particularly
      for treating poorly managed ulcers or traumatic wounds. Furthermore, in our anti
      inflammation-screening system, SJM significantly inhibited the expression of pro
      inflammatory proteins. Previous studies have yet to adopt an animal model to
      verify the phenomenon and described in the historical records regarding the
      efficacy of SJM in promoting wound healing. Besides, the mechanism of wound
      healing effect of SJM is also not clear. METHODS: This study applied in vitro and
      in vivo models, tissue section analysis, and western blotting to evaluate the
      effect of SJM on wound healing. The RAW 264.7 cells were used in anti
      inflammatory activity assay and phagocytic assay. Male Wistar rats were used to
      evaluate the effect of SJM on burn injury healing. A copper block (2 * 2 cm, 150
      g) preheated to 165  degrees C in a dry bath was used to contact the skin area
      for 10 s, thus creating a full-thickness burn injury. The results were analyzed
      by hematoxylin and eosin staining, picrosirius red staining and Western blotting.
      RESULTS: The results revealed that in the in vitro model, the presence of SJM
      decreased the inducible nitric oxide synthase (iNOS) expression and enhanced the
      functions of macrophages. The results of the rat burn injury model revealed that
      SJM decreased neutrophil infiltration, promoted wound healing, thus increasing
      the collagen I content and promoting the expression of transforming growth factor
      beta 1 (TGF-beta1) protein. We speculate that the effect and mechanism of SJM on
      promoting wound healing is related to macrophage activation. In the inflammation
      phase, SJM alleviates inflammation by inhibiting iNOS expression and removing
      neutrophils through phagocytosis. Furthermore, SJM induces the secretion of TGF
      beta1, converting collagen during the tissue remodeling phase. CONCLUSIONS:
      According to our review of relevant literature, this is the first study that
      applied an evidence-based method to verify that SJM alleviates inflammation,
      enhances phagocytosis, and triggers wound healing after burn injury. The study
      findings reveal that SJM provides a promising therapeutic option for treating
      burn injury.

PMID- 27894303
TI  - Integrated agriculture programs to address malnutrition in northern Malawi.
AB  - BACKGROUND: In countries where the majority of undernourished people are
      smallholder farmers, there has been interest in agricultural interventions to
      improve nutritional outcomes. Addressing gender inequality, however, is a key
      mechanism by which agriculture can improve nutrition, since women often play a
      crucial role in farming, food processing and child care, but have limited
      decision-making and control over agricultural resources. This study examines the
      approaches by which gender equity in agrarian, resource-poor settings can be
      improved using a case study in Malawi. METHODS: A quasi-experimental design with
      qualitative methods was used to examine the effects of a participatory
      intervention on gender relations. Thirty married couple households in 19 villages
      with children under the age of 5 years were interviewed before and then after the
      intervention. An additional 7 interviews were conducted with key informants, and
      participant observation was carried out before, during the intervention and
      afterwards in the communities. The interviews were recorded and transcribed, and
      analysed qualitatively for key themes, concepts and contradictions. RESULTS:
      Several barriers were identified that undermine the quality of child care
      practices, many linked to gender constructions and norms. The dominant concepts
      of masculinity created shame and embarrassment if men deviated from these norms,
      by cooking or caring for their children. The study provided evidence that
      participatory education supported new masculinities through public performances
      that encouraged men to take on these new roles. Invoking men's family
      responsibilities, encouraging new social norms alongside providing new
      information about different healthy recipes were all pathways by which men
      developed new 'emergent' masculinities in which they were more involved in
      cooking and child care. The transformational approach, intergenerational and
      intra-gendered events, a focus on agriculture and food security, alongside
      involving male leaders were some of the reasons that respondents named for
      changed gender norms. CONCLUSIONS: Participatory education that explicitly
      addresses hegemonic masculinities related to child nutrition, such as women's
      roles in child care, can begin to change dominant gender norms. Involving male
      leaders, participatory methods and integrating agriculture and food security
      concerns with nutrition appear to be key components in the context of agrarian
      communities.

PMID- 27894305
TI  - Identification of molecular determinants of cell culture growth characteristics
      of Enterovirus 71.
AB  - BACKGROUND: Hand, foot and mouth disease is caused by Enterovirus 71 (EV-A71) and
      Coxsackieviruses. EV-A71 infection is associated with high fever, rashes and
      ulcers but more severe symptoms such as cardiopulmonary failure and death have
      been reported. The lack of vaccines highlighted the urgency of developing
      preventive agents against EV-A71. The molecular determinants of virulent
      phenotypes of EV-A71 is unclear. It remains to be investigated if specific
      molecular determinants would affect the cell culture growth characteristics of
      the EV-A71 fatal strain in Rhabdomyosarcoma (RD) cells. RESULTS: In this study,
      several genetically modified sub-genotype B4 EV-A71 mutants were constructed by
      site-directed mutations at positions 158, 475, 486, 487 and 5262 or through
      partial deletion of the 5'-NTR region (? 11 bp from nt 475 to 486) to generate a
      deletion mutant (PD). EV-A71 mutants 475 and PD caused minimal cytopathic
      effects, produced lowest viral RNA copy number, viral particles as well as
      minimal amount of viral protein (VP1) in RD cells when compared to mutants 158,
      486, 487 and 5262. CONCLUSIONS: The molecular determinants of virulent phenotypes
      of EV-A71 sub-genotype B4 strain 41 (5865/Sin/000009) were found to differ from
      the C158 molecular determinant reported for the fatal EV-A71 sub-genotype B1
      strain (clinical isolate 237). The site-directed mutations (SDM) introduced at
      various sites of the cDNA affected growth of the various mutants when compared to
      the wild type. Lowest viral RNA copy number, minimal number of plaques formed,
      higher infectious doses required for 50% lethality of RD cells and much reduced
      VP1 of the EV-A71 sub-genotype B4 strain 41 genome was attained in mutants
      carrying SDM at position 475 and through partial deletion of 11 bp at the 5'-NTR
      region.

PMID- 27894304
TI  - Brain inflammation is accompanied by peripheral inflammation in Cstb -/- mice, a
      model for progressive myoclonus epilepsy.
AB  - Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal
      recessively inherited childhood-onset neurodegenerative disorder, characterized
      by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB)
      underlie EPM1. The CSTB-deficient (Cstb -/- ) mouse model recapitulates key
      features of EPM1, including myoclonic seizures. The mice show early microglial
      activation that precedes seizure onset and neuronal loss and leads to
      neuroinflammation. We here characterized the inflammatory phenotype of Cstb -/-
      mice in more detail. We found higher concentrations of chemokines and pro
      inflammatory cytokines in the serum of Cstb -/- mice and higher CXCL13 expression
      in activated microglia in Cstb -/- compared to control mouse brains. The elevated
      chemokine levels were not accompanied by blood-brain barrier disruption, despite
      increased brain vascularization. Macrophages in the spleen and brain of Cstb -/-
      mice were predominantly pro-inflammatory. Taken together, these data show that
      CXCL13 expression is a hallmark of microglial activation in Cstb -/- mice and
      that the brain inflammation is linked to peripheral inflammatory changes, which
      might contribute to the disease pathology of EPM1.

PMID- 27894307
TI  - Regional health workforce monitoring as governance innovation: a German model to
      coordinate sectoral demand, skill mix and mobility.
AB  - BACKGROUND: As health workforce policy is gaining momentum, data sources and
      monitoring systems have significantly improved in the European Union and
      internationally. Yet data remain poorly connected to policy-making and
      implementation and often do not adequately support integrated approaches. This
      brings the importance of governance and the need for innovation into play. CASE:
      The present case study introduces a regional health workforce monitor in the
      German Federal State of Rhineland-Palatinate and seeks to explore the capacity of
      monitoring to innovate health workforce governance. The monitor applies an
      approach from the European Network on Regional Labour Market Monitoring to the
      health workforce. The novel aspect of this model is an integrated, procedural
      approach that promotes a 'learning system' of governance based on three
      interconnected pillars: mixed methods and bottom-up data collection, strong
      stakeholder involvement with complex communication tools and shared decision- and
      policy-making. Selected empirical examples illustrate the approach and the tools
      focusing on two aspects: the connection between sectoral, occupational and
      mobility data to analyse skill/qualification mixes and the supply-demand matches
      and the connection between monitoring and stakeholder-driven policy. CONCLUSION:
      Regional health workforce monitoring can promote effective governance in high
      income countries like Germany with overall high density of health workers but
      maldistribution of staff and skills. The regional stakeholder networks are cost
      effective and easily accessible and might therefore be appealing also to low- and
      middle-income countries.

PMID- 27894306
TI  - First Phase I human clinical trial of a killed whole-HIV-1 vaccine: demonstration
      of its safety and enhancement of anti-HIV antibody responses.
AB  - BACKGROUND: Vaccination with inactivated (killed) whole-virus particles has been
      used to prevent a wide range of viral diseases. However, for an HIV vaccine this
      approach has been largely negated due to inherent safety concerns, despite the
      ability of killed whole-virus vaccines to generate a strong, predominantly
      antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically
      modified by deleting the nef and vpu genes and substituting the coding sequence
      for the Env signal peptide with that of honeybee melittin signal peptide to
      produce a less virulent and more replication efficient virus. This genetically
      modified virus (gmHIV-1NL4-3) was inactivated and formulated as a killed whole
      HIV vaccine, and then used for a Phase I human clinical trial (Trial
      Registration: Clinical Trials NCT01546818). The gmHIV-1NL4-3 was propagated in
      the A3.01 human T cell line followed by virus purification and inactivation with
      aldrithiol-2 and gamma-irradiation. Thirty-three HIV-1 positive volunteers
      receiving cART were recruited for this observer-blinded, placebo-controlled Phase
      I human clinical trial to assess the safety and immunogenicity. RESULTS:
      Genetically modified and killed whole-HIV-1 vaccine, SAV001, was well tolerated
      with no serious adverse events. HIV-1NL4-3-specific PCR showed neither evidence
      of vaccine virus replication in the vaccine virus-infected human T lymphocytes in
      vitro nor in the participating volunteers receiving SAV001 vaccine. Furthermore,
      SAV001 with adjuvant significantly increased the pre-existing antibody response
      to HIV-1 proteins. Antibodies in the plasma of vaccinees were also found to
      recognize HIV-1 envelope protein on the surface of infected cells as well as
      showing an enhancement of broadly neutralizing antibodies inhibiting tier I and
      II of HIV-1 B, D, and A subtypes. CONCLUSION: The killed whole-HIV vaccine,
      SAV001, is safe and triggers anti-HIV immune responses. It remains to be
      determined through an appropriate trial whether this immune response prevents HIV
      infection.

PMID- 27894308
TI  - Capacity evaluation for general practitioners in Pudong new area of Shanghai: an
      empirical study.
AB  - BACKGROUND: Building highly qualified General Practitioners (GPs) is key to the
      development of primary health care. It's therefore urgent to ensure the GPs'
      quality service under the background of the new round of health care system
      reforms in China. A new model of GP qualification examination was originally
      implemented in Pudong New Area of Shanghai, China, which aimed to empirically
      evaluate the GPs' capability in terms of clinical performance and social
      recognition. In the current study, an analysis was made of the first two years
      (2014-2015) of such theoretical and practical examinations on the GPs there with
      a view to getting a deep insight into the GP community so as to identify the
      barriers to such a form of GP qualification examination. METHODS: The agency
      survey method was applied to the two-year database of the GP examinees, the
      formative research conducted to explore the key elements for developing the
      examination model. The data analysis was performed with SPSS for Windows (Version
      19.0) to describe the GPs' overall characteristics, and to make comparisons
      between different groups. RESULTS: In 2015, the total number of GPs was 1264 in
      the area, in different districts of which, statistically significant differences
      were found in sex, age, professional title and employment span (P < 0.05). Such
      results were found to be similar to those in 2014. The examinees' theoretical
      scores were statistically different (F = 7.76; P < 0.05), showing a sloping trend
      from the urban district to the suburban, to the rural and then to the farther
      rural, as indicated by LSD-t test (P < 0.05). From the theoretical examinations
      the scores were higher on the western medicine than on the traditional Chinese
      medicine (F = 22.11; P < 0.05). CONCLUSIONS: As suggested by the current study on
      the GPs' qualification examination, which was pioneered in Pudong New Area of
      Shanghai, the construction of GP community was far from sufficient. It was a
      preliminary study and further studies are merited along the construction and
      development in terms of continuing medical education, performance appraisal and
      incentive mechanism.

PMID- 27894309
TI  - Analysis of long noncoding RNA expression in hepatocellular carcinoma of
      different viral etiology.
AB  - BACKGROUND: Dysregulation of long noncoding RNA (lncRNA) expression contributes
      to the pathogenesis of many human diseases, including liver diseases. Several
      lncRNAs have been reported to play a role in the development of hepatocellular
      carcinoma (HCC). However, most studies have analyzed lncRNAs only in hepatitis B
      virus (HBV)-related HCC or in a single group of HCC patients regardless of the
      viral etiology. METHODS: To investigate whether lncRNAs are differentially
      expressed in HCC of different viral etiology, we profiled 101 disease-related
      lncRNAs, including 25 lncRNAs previously associated with HCC, in liver specimens
      obtained from well-characterized patients with HBV-, hepatitis C virus (HCV)-, or
      hepatitis D virus (HDV)-associated HCC. RESULTS: We identified eight novel HCC
      related lncRNAs that were significantly dysregulated in HCC tissues compared to
      their surrounding non-tumorous tissues. Some of these lncRNAs were significantly
      dysregulated predominantly in one specific hepatitis virus-related HCC, including
      PCAT-29 in HBV-related HCC, aHIF and PAR5 in HCV-related HCC, and Y3 in HDV
      related HCC. Among the lncRNAs previously reported in HCC, we found that DBH-AS1,
      hDREH and hPVT1 were differentially expressed in HCC of different viral etiology.
      CONCLUSIONS: Our study suggests that HCC of different viral etiology is regulated
      by different lncRNAs. The identification of lncRNAs unique to specific hepatitis
      virus-related HCC may provide new tools for improving the diagnosis of HCC and
      open new avenues for disease-specific therapeutic interventions.

PMID- 27894310
TI  - Monitoring change in volume of calcifications in juvenile idiopathic inflammatory
      myopathy: a pilot study using low dose computed tomography.
AB  - BACKGROUND: Dystrophic calcifications may occur in patients with J uvenile
      Idiopathic Inflammatory Myopathy (JIIM) as well as other connective tissue and
      metabolic diseases, but a reliable method of measuring the volume of these
      calcifications has not been established. The purpose of this study is to
      determine the feasibility of low dose, limited slice, Computed Tomography (CT) to
      measure objectively in-situ calcification volumes in patients with JIIM over
      time. METHODS: Ten JIIM patients (eight JDM, two Overlap) with calcifications
      were prospectively recruited over a 2-year period to undergo two limited, low
      dose, four-slice CT scans. Calculation of the volume of calcifications used a CT
      post processing workstation. Additional patient data included: Disease Activity
      Scores (DAS), Childhood Myositis Assessment Scale (CMAS), myositis specific
      antibodies (MSA), and the TNFalpha-308 promoter region A/G polymorphism.
      Statistical analysis utilized the Pearson correlation coefficient, the paired t
      test and descriptive statistics. RESULTS: Ten JIIM, mean age 14.54 +/- 4.54
      years, had a duration of untreated disease of 8.68 +/- 5.65 months  MSA status:
      U1RNP (1), PM-Scl (1), Ro (1, 4 indeterminate), p155/140 (2), MJ (3), Mi-2
      indeterminate (1), negative (3). 4/8 JDM (50%) were TNF-alpha-308 A+. Overall,
      the calcification volumes tended to decrease from the first to the second CT
      study by 0.5 cm3 (from 2.79 +/- 1.98 cm3 to 2.29 +/- 2.25 cm3). The average
      effective radiation dose was 0.007 +/- 0.002, 0.010 +/- 0.005, and 0.245 mSv for
      the upper extremity, lower extremity and chest, respectively (compared to a
      standard chest x-ray-- 0.02mSV effective dosage). CONCLUSION: We conclude: 1) the
      limited low dose CT technique provides objective data about volume of the
      calcifications in JIIM; 2) measuring the volume of calcifications in an extremity
      is associated with minimal radiation exposure; 3) This method may be useful to
      evaluate the efficacy of therapies for JIIM dystrophic calcification.

PMID- 27894311
TI  - Access to substance use treatment among young adults who use prescription opioids
      non-medically.
AB  - BACKGROUND: Non-medical prescription opioid (NMPO) use is a substantial public
      health problem in the United States, with 1.5 million new initiates annually.
      Only 746,000 people received treatment for NMPO use in 2013, demonstrating
      substantial disparities in access to treatment. This study aimed to assess
      correlates of accessing substance use treatment among young adult NMPO users in
      Rhode Island, a state heavily impacted by NMPO use and opioid overdose. METHODS:
      This analysis uses data from a study of 200 Rhode Island residents aged 18 to 29
      who reported NMPO use in the past 30 days. We compared individuals who had ever
      successfully enrolled in a substance use treatment program without ever facing
      barriers, individuals who had ever attempted to enroll but were unable, and
      individuals who never attempted to enroll. We used multinomial logistic
      regression to determine the independent correlates of never attempting and
      unsuccessfully attempting to access substance use treatment. RESULTS: Among 200
      participants, the mean age was 24.5, 65.5% were male, and 61.5% were white.
      Nearly half (45.5%) had never attempted to enroll in substance use treatment,
      while 35.0% had successfully enrolled without ever facing barriers and 19.5% were
      unsuccessful in at least one attempt to enroll. In multivariable models, non
      white participants were more likely to never have attempted to enroll compared to
      white participants. Previous incarceration, experiencing drug-related
      discrimination by the medical community, and a monthly income of $501 - $1500
      were associated with a decreased likelihood of never attempting to enroll. A
      history of overdose and a monthly income of $501 - $1500 were associated with an
      increased likelihood of unsuccessfully accessing treatment. The most commonly
      reported barriers to accessing treatment were waiting lists (n = 23), health
      insurance not approving enrollment (n = 20), and inability to pay (n = 16).
      CONCLUSIONS: This study demonstrates significant disparities in access to
      treatment among young adults who report NMPO use. A history of overdose was shown
      to correlate with experiencing barriers to substance use treatment utilization.
      Interventions are needed to reduce drug-related discrimination in clinical
      settings and to provide mechanisms that link young adults (particularly with a
      history of overdose) to evidence-based treatment.

PMID- 27894312
TI  - Release of copper-amended particles from micronized copper-pressure-treated wood
      during mechanical abrasion.
AB  - BACKGROUND: We investigated the particles released due to abrasion of wood
      surfaces pressure-treated with micronized copper azole (MCA) wood preservative
      and we gathered preliminary data on its in vitro cytotoxicity for lung cells. The
      data were compared with particles released after abrasion of untreated, water (0%
      MCA)-pressure-treated, chromated copper (CC)-pressure-treated wood, and varnished
      wood. Size, morphology, and composition of the released particles were analyzed.
      RESULTS: Our results indicate that the abrasion of MCA-pressure-treated wood does
      not cause an additional release of nanoparticles from the unreacted copper (Cu)
      carbonate nanoparticles from of the MCA formulation. However, a small amount of
      released Cu was detected in the nanosized fraction of wood dust, which could
      penetrate the deep lungs. The acute cytotoxicity studies were performed on a
      human lung epithelial cell line and human macrophages derived from a monocytic
      cell line. These cell types are likely to encounter the released wood particles
      after inhalation. CONCLUSIONS: Our findings indicate that under the experimental
      conditions chosen, MCA does not pose a specific additional nano-risk, i.e. there
      is no additional release of nanoparticles and no specific nano-toxicity for lung
      epithelial cells and macrophages.

PMID- 27894315
TI  - Reassessing the death risk related to probiotics in critically ill patients.

PMID- 27894313
TI  - Identifying the barriers and enablers for a triage, treatment, and transfer
      clinical intervention to manage acute stroke patients in the emergency
      department: a systematic review using the theoretical domains framework (TDF).
AB  - BACKGROUND: Clinical guidelines recommend that assessment and management of
      patients with stroke commences early including in emergency departments (ED). To
      inform the development of an implementation intervention targeted in ED, we
      conducted a systematic review of qualitative and quantitative studies to identify
      relevant barriers and enablers to six key clinical behaviours in acute stroke
      care: appropriate triage, thrombolysis administration, monitoring and management
      of temperature, blood glucose levels, and of swallowing difficulties and transfer
      of stroke patients in ED. METHODS: Studies of any design, conducted in ED, where
      barriers or enablers based on primary data were identified for one or more of
      these six clinical behaviours. Major biomedical databases (CINAHL, OVID SP
      EMBASE, OVID SP MEDLINE) were searched using comprehensive search strategies. The
      barriers and enablers were categorised using the theoretical domains framework
      (TDF). The behaviour change technique (BCT) that best aligned to the strategy
      each enabler represented was selected for each of the reported enablers using a
      standard taxonomy. RESULTS: Five qualitative studies and four surveys out of the
      44 studies identified met the selection criteria. The majority of barriers
      reported corresponded with the TDF domains of "environmental, context and
      resources" (such as stressful working conditions or lack of resources) and
      "knowledge" (such as lack of guideline awareness or familiarity). The majority of
      enablers corresponded with the domains of "knowledge" (such as education for
      physicians on the calculated risk of haemorrhage following intravenous
      thrombolysis [tPA]) and "skills" (such as providing opportunity to treat stroke
      cases of varying complexity). The total number of BCTs assigned was 18. The BCTs
      most frequently assigned to the reported enablers were "focus on past success"
      and "information about health consequences." CONCLUSIONS: Barriers and enablers
      for the delivery of key evidence-based protocols in an emergency setting have
      been identified and interpreted within a relevant theoretical framework. This new
      knowledge has since been used to select specific BCTs to implement evidence-based
      care in an ED setting. It is recommended that findings from similar future
      reviews adopt a similar theoretical approach. In particular, the use of existing
      matrices to assist the selection of relevant BCTs.

PMID- 27894314
TI  - Self-assembly of hexahistidine-tagged tobacco etch virus capsid protein into
      microfilaments that induce IgG2-specific response against a soluble porcine
      reproductive and respiratory syndrome virus chimeric protein.
AB  - BACKGROUND: Assembly of recombinant capsid proteins into virus-like particles
      (VLPs) still represents an interesting challenge in virus-based nanotechnologies.
      The structure of VLPs has gained importance for the development and design of new
      adjuvants and antigen carriers. The potential of Tobacco etch virus capsid
      protein (TEV CP) as adjuvant has not been evaluated to date. FINDINGS: Two
      constructs for TEV CP expression in Escherichia coli were generated: a wild-type
      version (TEV-CP) and a C-terminal hexahistidine (His)-tagged version (His-TEV
      CP). Although both versions were expressed in the soluble fraction of E. coli
      lysates, only His-TEV-CP self-assembled into micrometric flexuous filamentous
      VLPs. In addition, the His-tag enabled high yields and facilitated purification
      of TEV VLPs. These TEV VLPs elicited broader IgG2-specific antibody response
      against a novel porcine reproductive and respiratory syndrome virus (PRRSV)
      protein when compared to the potent IgG1 response induced by the protein alone.
      CONCLUSIONS: His-TEV CP was purified by immobilized metal affinity chromatography
      and assembled into VLPs, some of them reaching 2-MUm length. TEV VLPs
      administered along with PRRSV chimeric protein changed the IgG2/IgG1 ratio
      against the chimeric protein, suggesting that TEV CP can modulate the immune
      response against a soluble antigen.

PMID- 27894316
TI  - Dietary patterns in obese pregnant women; influence of a behavioral intervention
      of diet and physical activity in the UPBEAT randomized controlled trial.
AB  - BACKGROUND: Understanding dietary patterns in obese pregnant women will inform
      future intervention strategies to improve pregnancy outcomes and the health of
      the child. The aim of this study was to investigate the effect of a behavioral
      intervention of diet and physical activity advice on dietary patterns in obese
      pregnant woman participating in the UPBEAT study, and to explore associations of
      dietary patterns with pregnancy outcomes. METHODS: In the UPBEAT randomized
      controlled trial, pregnant obese women from eight UK multi-ethnic, inner-city
      populations were randomly assigned to receive a diet/physical activity
      intervention or standard antenatal care. The dietary intervention aimed to reduce
      glycemic load and saturated fat intake. Diet was assessed using a food frequency
      questionnaire (FFQ) at baseline (15+0-18+6 weeks' gestation), post intervention
      (27+0-28+6 weeks) and in late pregnancy (34+0-36+0 weeks). Dietary patterns were
      characterized using factor analysis of the baseline FFQ data, and changes
      compared in the control and intervention arms. Patterns were related to pregnancy
      outcomes in the combined control/intervention cohort (n = 1023). RESULTS: Four
      distinct baseline dietary patterns were defined; Fruit and vegetables,
      African/Caribbean, Processed, and Snacks, which were differently associated with
      social and demographic factors. The UPBEAT intervention significantly reduced the
      Processed (-0.14; 95% CI -0.19, -0.08, P <0.0001) and Snacks (-0.24; 95% CI 
      0.31, -0.17, P <0.0001) pattern scores. In the adjusted model, baseline scores
      for the African/Caribbean (quartile 4 compared with quartile 1: OR = 2.46; 95% CI
      1.41, 4.30) and Processed (quartile 4 compared with quartile 1: OR = 2.05; 95% CI
      1.23, 3.41) patterns in the entire cohort were associated with increased risk of
      gestational diabetes. CONCLUSIONS: In a diverse cohort of obese pregnant women an
      intensive dietary intervention improved Processed and Snack dietary pattern
      scores. African/Caribbean and Processed patterns were associated with an
      increased risk of gestational diabetes, and provide potential targets for future
      interventions. TRIAL REGISTRATION: Current controlled trials; ISRCTN89971375.

PMID- 27894317
TI  - The impact of shift and night work on health related quality of life of working
      women: findings from the Korea Health Panel.
AB  - BACKGROUND: Night and shift work status has been associated with health related
      quality of life (HRQoL) in economically active women. This study aimed to
      investigate the association between night or shift work status and HRQoL of
      economically active women and to further analyze how marital status interplays in
      the objected relationship. METHODS: Data were from the Korea Health Panel, 2011
      to 2013. A total of 2238 working women were included for analysis. Work status
      was categorized into day work, night work, and rotating shift work and its
      association with HRQoL, measured using the EuroQol-5D (EQ-5D) index, was
      investigated using the generalized estimating equation (GEE) model. RESULTS:
      Compared to the day work reference group, the night work group (beta: -0.9757, P
      = 0.0202) and the rotating shift work group (beta: -0.7947, P = 0.0363) showed
      decreases in EQ-5D scores. This trend was maintained regardless of marital
      status, although decreases in health related quality of life were particularly
      pronounced among night shift workers with a spouse. CONCLUSION: Night and
      rotating shift work status was associated with HRQoL of economically active women
      as individuals working night and rotating shifts showed decreases in EQ-5D scores
      compared to individuals working day shifts. The findings of this study signify
      the importance of monitoring the HRQoL status of women working night and rotating
      shifts as these individuals may be comparatively vulnerable to reduced HRQoL.

PMID- 27894319
TI  - Erratum to: Detection of ATM germline variants by the p53 mitotic centrosomal
      localization test in BRCA1/2-negative patients with early-onset breast cancer.

PMID- 27894318
TI  - Surgical treatment of recurrent urachal carcinoma with liver metastasis: a case
      report and literature review.
AB  - BACKGROUND: Urachal carcinoma is a rare malignancy with poor prognosis due to
      late presentation of the disease and its aggressiveness. Surgery remains the
      mainstay of therapy even in cases of disease recurrence. To the best of our
      knowledge, this is the first report of salvage surgery in the case of urachal
      carcinoma with liver metastasis. CASE PRESENTATION: The patient was a young woman
      who suffered from locally advanced urachal carcinoma treated with en-bloc
      cystectomy, hysterectomy with bilateral adnexectomy, partial resection of the
      sigmoid colon, and partial resection of the rectus abdominis muscle with the
      fascia, skin, and umbilicus. Adjuvant chemotherapy with paclitaxel and
      carboplatin was applied. Two years after the treatment, she was diagnosed with a
      single liver metastasis and a local pelvic recurrence. In a two-step operation,
      the patient underwent right hemihepatectomy as well as resection of pelvic
      recurrence site and adjuvant chemotherapy with gemcitabine. Due to the disease
      progression, a complete resection of the lesions was not achieved and the
      response to chemotherapy was poor. The patient died of the disease after a year.
      CONCLUSIONS: Surgery is the first line of treatment for urachal carcinoma and
      should be always considered as an option in cases of disease recurrence. Radical
      initial surgical management, close patient surveillance, and prompt treatment of
      disease relapse may all contribute to prolonging patient's survival.

PMID- 27894320
TI  - Successful malaria elimination in the Ecuador-Peru border region: epidemiology
      and lessons learned.
AB  - BACKGROUND: In recent years, malaria (Plasmodium vivax and Plasmodium falciparum)
      has been successfully controlled in the Ecuador-Peru coastal border region. The
      aim of this study was to document this control effort and to identify the best
      practices and lessons learned that are applicable to malaria control and to other
      vector-borne diseases. A proximal outcome evaluation was conducted of the robust
      elimination programme in El Oro Province, Ecuador, and the Tumbes Region, Peru.
      Data collection efforts included a series of workshops with local public health
      experts who played central roles in the elimination effort, review of
      epidemiological records from Ministries of Health, and a review of national
      policy documents. Key programmatic and external factors are identified that
      determined the success of this eradication effort. CASE DESCRIPTION: From the mid
      1980s until the early 2000s, the region experienced a surge in malaria
      transmission, which experts attributed to a combination of ineffective anti
      malarial treatment, social-ecological factors (e.g., El Nino, increasing rice
      farming, construction of a reservoir), and political factors (e.g., reduction in
      resources and changes in management). In response to the malaria crisis, local
      public health practitioners from El Oro and Tumbes joined together in the mid
      1990s to forge an unofficial binational collaboration for malaria control. Over
      the next 20 years, they effectively eradicated malaria in the region, by
      strengthening surveillance and treatment strategies, sharing of resources,
      operational research to inform policy, and novel interventions. DISCUSSION AND
      EVALUATION: The binational collaboration at the operational level was the
      fundamental component of the successful malaria elimination programme. This
      unique relationship created a trusting, open environment that allowed for
      flexibility, rapid response, innovation and resilience in times of crisis, and
      ultimately a sustainable control programme. Strong community involvement, an
      extensive microscopy network and ongoing epidemiologic investigations at the
      local level were also identified as crucial programmatic strategies. CONCLUSION:
      The results of this study provide key principles of a successful malaria
      elimination programme that can inform the next generation of public health
      professionals in the region, and serve as a guide to ongoing and future control
      efforts of other emerging vector borne diseases globally.

PMID- 27894321
TI  - Encephalomyocarditis virus infection in Macaca sylvanus and Hystrix cristata from
      an Italian rescue centre for wild and exotic animals.
AB  - BACKGROUND: The Encephalomyocarditis virus (EMCV) is a small, non enveloped,
      positive sense single-stranded RNA virus in the genus Cardiovirus, family
      Picornaviridae, with two known serotypes. It is spread worldwide and infects a
      huge range of vertebrate hosts with zoonotic potential for humans. The pig is the
      mammal most likely to be impacted on with the disease, but EMCV occurrence has
      also been reported in non-human primates and in a variety of domestic, captive
      and wild animals. Until now, human cases have been very rare and the risk appears
      to be almost negligible in spite of human susceptibility to the infection. CASE
      PRESENTATION: Between September and November 2012 a fatal Encephalomyocarditis
      virus outbreak involving four Barbary macaques and 24 crested porcupines occurred
      at a rescue centre for wild and exotic animals in Central Italy. In this open
      field zoo park located near Grosseto, Tuscany about 1000 animals belonging to
      different species, including various non-human primates were hosted at that time.
      Sudden deaths were generally observed without any evident symptoms or only with
      mild nonspecific clinical signs. The major gross change was characterised by grey
      white necrotic foci in the myocardium and the same EMCV strain was isolated both
      in macaques and crested porcupines. Phylogenetic analysis has confirmed that only
      one EMCV strain is circulating in Italy, capable of infecting different animal
      species. CONCLUSIONS: This report confirms the susceptibility of non-human
      primates to the EMCV infection and describes the disease in porcupine, a common
      wild Italian and African species. No human cases were observed, but given the
      zoonotic potential of EMCV these findings are of importance in the context of
      animal-human interface.

PMID- 27894322
TI  - Identification of Escherichia coli and Trueperella pyogenes isolated from the
      uterus of dairy cows using routine bacteriological testing and Fourier transform
      infrared spectroscopy.
AB  - BACKGROUND: Uterine disorders are common postpartum diseases in dairy cows. In
      practice, uterine treatment is often based on systemic or locally applied
      antimicrobials with no previous identification of pathogens. Accurate on-farm
      diagnostics are not available, and routine testing is time-consuming and cost
      intensive. An accurate method that could simplify the identification of uterine
      pathogenic bacteria and improve pathogen-specific treatments could be an
      important advance to practitioners. The objective of the present study was to
      evaluate whether a database built with uterine bacteria from European dairy cows
      could be used to identify bacteria from Argentinean cows by Fourier transformed
      infrared (FTIR) spectroscopy. Uterine samples from 64 multiparous dairy cows with
      different types of vaginal discharge (VD) were collected between 5 and 60 days
      postpartum, analyzed by routine bacteriological testing methods and then re
      evaluated by FTIR spectroscopy (n = 27). RESULTS: FTIR spectroscopy identified
      Escherichia coli in 12 out of 14 samples and Trueperella pyogenes in 8 out of 10
      samples. The agreement between the two methods was good with a Kappa coefficient
      of 0.73. In addition, the likelihood for bacterial growth of common uterine
      pathogens such as E. coli and T. pyogenes tended to increase with VD score. The
      odds for a positive result to E. coli or T. pyogenes was 1.88 times higher in
      cows with fetid VD than in herdmates with clear normal VD. CONCLUSIONS: We
      conclude that the presence of E. coli and T. pyogenes in uterine samples from
      Argentinean dairy cows can be detected with FTIR with the use of a database built
      with uterine bacteria from European dairy cows. Future studies are needed to
      determine if FTIR can be used as an alternative to routine bacteriological
      testing methods.

PMID- 27894323
TI  - Health-related quality of life and a cost-utility simulation of adults in the UK
      with osteogenesis imperfecta, X-linked hypophosphatemia and fibrous dysplasia.
AB  - BACKGROUND: Health-related quality of life of adults with osteogenesis imperfecta
      (OI), fibrous dysplasia (FD) and X-linked hypophosphatemia (XLH) remains poorly
      described. The aim of this study was to describe the HRQoL of adults with
      osteogenesis imperfecta, fibrous dysplasia and X-linked hypophophataemia and
      perform a cost-utility simulation to calculate the maximum cost that a health
      care system would be willing to pay for a hypothetical treatment of a rare bone
      disease. RESULTS: Participants completed the EQ-5D-5 L questionnaire between
      September 2014 and March 2016. For the economic simulation, we considered a
      hypothetical treatment that would be applied to OI participants in the lower
      tertile of the health utility score. A total of 109 study participants fully
      completed the EQ-5D-5 L questionnaire (response rate 63%). Pain/discomfort was
      the most problematic domain for participants with all three diseases (FD 31%, XLH
      25%, OI 16%). The economic simulation identified an expected treatment impact of
      +2.5 QALYs gained per person during the 10-year period, which led to a willing to
      pay of L14,355 annually for a health care system willing to pay up to L50,000 for
      each additional QALY gained by an intervention. CONCLUSIONS: This is the first
      study to quantitatively measure and compare the HRQoL of adults with OI, FD and
      XLH and the first to use such data to conduct an economic simulation leading to
      healthcare system willingness-to-pay estimates for treatment of musculoskeletal
      rare diseases at various cost-effectiveness thresholds.

PMID- 27894324
TI  - Erratum to: Expression and methylation patterns partition luminal-A breast tumors
      into distinct prognostic subgroups.

PMID- 27894325
TI  - Identification of COL1A1 and COL1A2 as candidate prognostic factors in gastric
      cancer.
AB  - BACKGROUND: The role of type I collagen, composed of collagen type I alpha 1
      (COL1A1) and collagen type I alpha 2 (COL1A2), has been studied in several
      cancers. However, the expression of COL1A1 and COL1A2 in malignant, premalignant,
      and normal gastric tissues and their clinical significances in gastric cancer
      have not been elucidated. METHODS: Real-time quantitative PCR was performed in 55
      malignant, 27 premalignant, and 19 normal tissues to measure COL1A1 and COL1A2
      messenger RNA (mRNA) expression, and the correlations between COL1A1 and COL1A2
      expression and clinicopathological parameters and patients' survival rate were
      analyzed. RESULTS: We found that COL1A1 mRNA expression was significantly
      upregulated in premalignant and malignant tissues than in normal tissues, whereas
      COL1A2 mRNA expression was significantly higher in malignant tissues than in
      premalignant and normal tissues. Moreover, COL1A1 expression was unrelated to
      clinicopathological parameters, while COL1A2 expression was positively related to
      tumor size and depth of invasion. Besides, higher COL1A1 and COL1A2 expression
      levels were related to lower overall survival. CONCLUSIONS: We find that COL1A1
      might have its potential as a monitoring factor to screen early gastric cancer,
      and COL1A1 and COL1A2 might predict poor clinical outcomes in gastric cancer
      patients.

PMID- 27894326
TI  - Preserved autoregulation of coronary flow after off-pump coronary artery bypass
      grafting: retrospective assessment of intraoperative transit time flowmetry with
      and without intra-aortic balloon counterpulsation.
AB  - BACKGROUND: Intra-aortic balloon pumping (IABP) markedly increases graft flow
      after coronary artery bypass grafting (CABG) with cardiopulmonary bypass. We
      sought to delineate the effects of IABP on graft flow after off-pump CABG
      (OPCAB). METHODS: The clinical records of 32 patients (25 male, 7 female; mean
      age: 70 +/- 9 years) who underwent OPCAB with IABP between January 2011 and May
      2015 were retrospectively reviewed. Thirteen patients (41%) had a history of
      myocardial infarction, and 13 patients (41%) had a history of percutaneous
      coronary intervention. In total, there were 76 bypass grafts with 102 distal
      anastomoses. These included 50 in situ or pedicled grafts and 26 aortocoronary
      grafts. After completion of the anastomoses, the heart was positioned normally,
      and graft flow with IABP was measured using transit-time flowmetry under stable
      circulation. Then, IABP was turned off for 30 s to a few minutes, until graft
      flow was constant, for measurement of flow off IABP. RESULTS: The angiographic
      patency rate was 100% (47/47). Overall, graft flow was 55 +/- 36 ml/min on IABP
      and 53 +/- 36 ml/min off IABP (p = 0.37). The pulsatility index was 4.1 +/- 2.1
      on IABP and 2.7 +/- 1.5 off IABP (p < 0.001). There was no significant difference
      in graft flow between on and off IABP for aortocoronary bypass or in situ grafts.
      Graft flow was 57 +/- 36 ml/min on IABP and 55 +/- 37 ml/min off IABP (p = 0.41)
      in in situ grafts and 52 +/- 34 ml/min on IABP and 49 +/- 35 off IABP (p = 0.41)
      in aortocoronary grafts. Graft flow on IABP was more than 5 ml/min greater in 28
      (37%) bypass grafts, and more than 5 ml/min lower in 20 (26%) bypass grafts.
      CONCLUSION: In contrast to previous reports for conventional CABG, graft flow
      after OPCAB was not necessarily increased by IABP, regardless of elevated
      diastolic arterial pressure. It is suggested that preserved autoregulation of
      coronary flow contributes to a lower impact on the heart and early functional
      recovery, and consequently, greater perioperative safety of OPCAB.

PMID- 27894327
TI  - A statistical analysis protocol for the time-differentiated target temperature
      management after out-of-hospital cardiac arrest (TTH48) clinical trial.
AB  - BACKGROUND: The TTH48 trial aims to determine whether prolonged duration (48
      hours) of targeted temperature management (TTM) at 33 (+/-1)  degrees C results
      in better neurological outcomes compared to standard duration (24 hours) after
      six months in comatose out-of-hospital cardiac arrest (OHCA) patients. METHODS:
      TTH48 is an investigator-initiated, multicentre, assessor-blinded, randomised,
      controlled superiority trial of 24 and 48 hours of TTM at 33 (+/-1)  degrees  C
      performed in 355 comatose OHCA patients aged 18 to 80 years who were admitted to
      ten intensive care units (ICUs) in six Northern European countries. The primary
      outcome of the study is the Cerebral Performance Category (CPC) score observed at
      six months after cardiac arrest. CPC scores of 1 and 2 are defined as good
      neurological outcomes, and CPC scores of 3, 4 and 5 are defined as poor
      neurological outcomes. The secondary outcomes are as follows: mortality within
      six months after cardiac arrest, CPC at hospital discharge, Glasgow Coma Scale
      (GCS) score on day 4, length of stay in ICU and at hospital and the presence of
      any adverse events such as cerebral, circulatory, respiratory, gastrointestinal,
      renal, metabolic measures, infection or bleeding. With the planned sample size,
      we have 80% power to detect a 15% improvement in good neurological outcomes at a
      two-sided statistical significance level of 5%. DISCUSSION: We present a detailed
      statistical analysis protocol (SAP) that specifies how primary and secondary
      outcomes should be evaluated. We also predetermine covariates for adjusted
      analyses and pre-specify sub-groups for sensitivity analyses. This pre-planned
      SAP will reduce analysis bias and add validity to the findings of this trial on
      the effect of length of TTM on important clinical outcomes after cardiac arrest.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT01689077 , 17 September 2012.

PMID- 27894328
TI  - Effect of driving pressure on mortality in ARDS patients during lung protective
      mechanical ventilation in two randomized controlled trials.
AB  - BACKGROUND: Driving pressure (DeltaPrs) across the respiratory system is
      suggested as the strongest predictor of hospital mortality in patients with acute
      respiratory distress syndrome (ARDS). We wonder whether this result is related to
      the range of tidal volume (VT). Therefore, we investigated DeltaPrs in two trials
      in which strict lung-protective mechanical ventilation was applied in ARDS. Our
      working hypothesis was that DeltaPrs is a risk factor for mortality just like
      compliance (Crs) or plateau pressure (Pplat,rs) of the respiratory system.
      METHODS: We performed secondary analysis of data from 787 ARDS patients enrolled
      in two independent randomized controlled trials evaluating distinct adjunctive
      techniques while they were ventilated as in the low VT arm of the ARDSnet trial.
      For this study, we used VT, positive end-expiratory pressure (PEEP), Pplat,rs,
      Crs, DeltaPrs, and respiratory rate recorded 24 hours after randomization, and
      compared them between survivors and nonsurvivors at day 90. Patients were
      followed for 90 days after inclusion. Cox proportional hazard modeling was used
      for mortality at day 90. If colinearity between DeltaPrs, Crs, and Pplat,rs was
      verified, specific Cox models were used for each of them. RESULTS: Both trials
      enrolled 805 patients of whom 787 had day-1 data available, and 533 of these
      survived. In the univariate analysis, DeltaPrs averaged 13.7 +/- 3.7 and 12.8 +/-
      3.7 cmH2O (P = 0.002) in nonsurvivors and survivors, respectively. Colinearity
      between DeltaPrs, Crs and Pplat,rs, which was expected as these variables are
      mathematically coupled, was statistically significant. Hazard ratios from the Cox
      models for day-90 mortality were 1.05 (1.02-1.08) (P = 0.005), 1.05 (1.01-1.08)
      (P = 0.008) and 0.985 (0.972-0.985) (P = 0.029) for DeltaPrs, Pplat,rs and Crs,
      respectively. PEEP and VT were not associated with death in any model.
      CONCLUSIONS: When ventilating patients with low VT, DeltaPrs is a risk factor for
      death in ARDS patients, as is Pplat,rs or Crs. As our data originated from trials
      from which most ARDS patients were excluded due to strict inclusion and exclusion
      criteria, these findings must be validated in independent observational studies
      in patients ventilated with a lung protective strategy. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT00299650 . Registered 6 March 2006 for the Acurasys trial.
      Clinicaltrials.gov NCT00527813 . Registered 10 September 2007 for the Proseva
      trial.

PMID- 27894329
TI  - Efficacy of early controlled motion of the ankle compared with no motion after
      non-operative treatment of an acute Achilles tendon rupture: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Early controlled ankle motion is widely used in the non-operative
      treatment of acute Achilles tendon rupture, though its safety and efficacy have
      never been investigated in a randomized setup. The objectives of this study are
      to investigate if early controlled motion of the ankle affects functional and
      patient-reported outcomes. METHODS/DESIGN: The study is performed as a blinded,
      randomized, controlled trial with patients allocated in a 1:1 ratio to one of two
      parallel groups. Patients aged from 18 to 70 years are eligible for inclusion.
      The intervention group performs early controlled motion of the ankle in weeks 3-8
      after rupture. The control group is immobilized. In total, 130 patients will be
      included from one big orthopedic center over a period of 21/2 years. The primary
      outcome is the patient-reported Achilles tendon Total Rupture Score evaluated at
      12 months post-injury. Secondary outcome measures are the heel-rise work test,
      Achilles tendon elongation, and the rate of re-rupture. The primary analysis will
      be conducted as intention-to-treat analyses. DISCUSSION: This trial is the first
      to investigate the safety and efficacy of early controlled motion in the
      treatment of acute Achilles tendon rupture in a randomized setup. The study uses
      the patient-reported outcome measure, the Achilles tendon Total Rupture Score, as
      the primary endpoint, as it is believed to be the best surrogate measure for the
      tendon's actual capability to function in everyday life. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT02015364 . Registered on 13 December 2013.

PMID- 27894331
TI  - A systematic review of patient safety in mental health: a protocol based on the
      inpatient setting.
AB  - BACKGROUND: Despite the growing international interest in patient safety as a
      discipline, there has been a lack of exploration of its application to mental
      health. It cannot be assumed that findings based upon physical health in acute
      care hospitals can be applied to mental health patients, disorders and settings.
      To the authors' knowledge, there has only been one review of the literature that
      focuses on patient safety research in mental health settings, conducted in Canada
      in 2008. We have identified a need to update this review and develop the
      methodology in order to strengthen the findings and disseminate internationally
      for advancement in the field. This systematic review will explore the existing
      research base on patient safety in mental health within the inpatient setting.
      METHODS: To conduct this systematic review, a thorough search across multiple
      databases will be undertaken, based upon four search facets ("mental health",
      "patient safety", "research" and "inpatient setting"). The search strategy has
      been developed based upon the Canadian review accompanied with input from the
      National Reporting and Learning System (NRLS) taxonomy of patient safety
      incidents and the Diagnostic and Statistical Manual of Mental Disorders (fifth
      edition). The screening process will involve perspectives from at least two
      researchers at all stages with a third researcher invited to review when
      discrepancies require resolution. Initial inclusion and exclusion criteria have
      been developed and will be refined iteratively throughout the process. Quality
      assessment and data extraction of included articles will be conducted by at least
      two researchers. A data extraction form will be developed, piloted and iterated
      as necessary in accordance with the research question. Extracted information will
      be analysed thematically. DISCUSSION: We believe that this systematic review will
      make a significant contribution to the advancement of patient safety in mental
      health inpatient settings. The findings will enable the development and
      implementation of interventions to improve the quality of care experienced by
      patients and support the identification of future research priorities. SYSTEMATIC
      REVIEW REGISTRATION: PROSPERO CRD42016034057.

PMID- 27894330
TI  - Marek's disease in chickens: a review with focus on immunology.
AB  - Marek's disease (MD), caused by Marek's disease virus (MDV), is a commercially
      important neoplastic disease of poultry which is only controlled by mass
      vaccination. Importantly, vaccines that can provide sterile immunity and inhibit
      virus transmission are lacking; such that vaccines are only capable of preventing
      neuropathy, oncogenic disease and immunosuppression, but are unable to prevent
      MDV transmission or infection, leading to emergence of increasingly virulent
      pathotypes. Hence, to address these issues, developing more efficacious vaccines
      that induce sterile immunity have become one of the important research goals for
      avian immunologists today. MDV shares very close genomic functional and
      structural characteristics to most mammalian herpes viruses such as herpes
      simplex virus (HSV). MD also provides an excellent T cell lymphoma model for
      gaining insights into other herpesvirus-induced oncogenesis in mammals and birds.
      For these reasons, we need to develop an in-depth knowledge and understanding of
      the host-viral interaction and host immunity against MD. Similarly, the
      underlying genetic variation within different chicken lines has a major impact on
      the outcome of infection. In this review article, we aim to investigate the
      pathogenesis of MDV infection, host immunity to MD and discuss areas of research
      that need to be further explored.

PMID- 27894334
TI  - How resilient is the general population to heatwaves? A knowledge survey from the
      ENHANCE project in Brussels and Amsterdam.
AB  - BACKGROUND: Studies have shown an increase in mortality and morbidity during
      heatwaves, especially among the elderly. We assessed the knowledge of the general
      population of Brussels and Amsterdam on groups at risk and protective measures
      for heat-related health effects. RESULTS: Six locations with mixed populations
      were selected in each city. Passer-by's in both cities were asked to participate
      in a short survey. Respondents in Brussels (n = 120) had significantly more
      knowledge on risk groups and protective measures than respondents in Amsterdam (n
      = 133). In both cities, individuals with higher education had better knowledge on
      risk groups and protective measures than individuals with lower education.
      CONCLUSIONS: Efforts at heat-awareness raising must be strengthened, especially
      in Amsterdam, and public health actions should effectively target vulnerable
      groups with lower education in both cities.

PMID- 27894332
TI  - Consideration of health inequalities in systematic reviews: a mapping review of
      guidance.
AB  - BACKGROUND: Given that we know that interventions shown to be effective in
      improving the health of a population may actually widen the health inequalities
      gap while others reduce it, it is imperative that all systematic reviewers
      consider how the findings of their reviews may impact (reduce or increase) on the
      health inequality gap. This study reviewed existing guidance on incorporating
      considerations of health inequalities in systematic reviews in order to examine
      the extent to which they can help reviewers to incorporate such issues. METHODS:
      A mapping review was undertaken to identify guidance documents that purported to
      inform reviewers on whether and how to incorporate considerations of health
      inequalities. Searches were undertaken in Medline, CINAHL and The Cochrane
      Library Methodology Register. Review guidance manuals prepared by international
      organisations engaged in undertaking systematic reviews, and their associated
      websites were scanned. Studies were included if they provided an overview or
      discussed the development and testing of guidance for dealing with the
      incorporation of considerations of health inequalities in evidence synthesis.
      Results are summarised in narrative and tabular forms. RESULTS: Twenty guidance
      documents published between 2009 and 2016 were included. Guidance has been
      produced to inform considerations of health inequalities at different stages of
      the systematic review process. The Campbell and Cochrane Equity Group have been
      instrumental in developing and promoting such guidance. Definitions of health
      inequalities and guidance differed across the included studies. All but one
      guidance document were transparent in their method of production. Formal methods
      of evaluation were reported for six guidance documents. Most of the guidance was
      operationalised in the form of examples taken from published systematic reviews.
      The number of guidance items to operationalise ranges from 3 up to 26 with a
      considerable overlap noted. CONCLUSIONS: Adhering to the guidance will require
      more work for the reviewers. It requires a deeper understanding of how reviewers
      can operationalise the guidance taking into consideration the barriers and
      facilitators involved. This has implications not only for understanding the
      usefulness and burden of the guidance but also for the uptake of guidance and its
      ultimate goal of improving health inequalities considerations in systematic
      reviews.

PMID- 27894333
TI  - Head-and-neck squamous cell carcinoma risk in smokers: no association detected
      between phenotype and AHR, CYP1A1, CYP1A2, or CYP1B1 genotype.
AB  - BACKGROUND: Head-and-neck squamous cell carcinoma (HNSCC) differs between smokers
      and nonsmokers in etiology and clinical presentation. Because of demonstrated
      unequivocal involvement in smoking-induced cancer in laboratory animals, four
      candidate genes--AHR, CYP1A1, CYP1A2, and CYP1B1--were selected for a clinical
      genotype-phenotype association study of HNSCC risk in smokers. Thirty-six single
      nucleotide variants (mostly tag-SNPs) within and near these four genes [16 (AHR),
      4 (CYP1A1), 4 (CYP1A2), and 12 (CYP1B1)] were chosen. METHODS: Extreme discordant
      phenotype (EDP) method of analysis was used to increase statistical power. HNSCC
      patients--having smoked 1-40 cigarette pack-years--represented the "highly
      sensitive" (HS) population; heavy smokers having smoked >=80 cigarette-pack-years
      without any type of cancer comprised the "highly-resistant" (HR) group. The vast
      majority of smokers were intermediate and discarded from consideration.
      Statistical tests were performed on N = 112 HS and N = 99 HR DNA samples from
      whole blood. CONCLUSIONS: Among the four genes and flanking regions--one
      haploblock, ACTTGATC in the 5' portion of CYP1B1, retained statistical
      significance after 100,000 permutations (P = 0.0042); among our study population,
      this haploblock was found in 36.4% of African-American, but only 1.49% of
      Caucasian, HNSCC chromosomes. Interestingly, in the 1000 Genomes Project
      database, frequency of this haplotype (in 1322 African and 1006 Caucasian
      chromosomes) is 0.356 and 0.003, respectively. This study represents an excellent
      example of "spurious association by population stratification". Considering the
      cohort size, we therefore conclude that the variant alleles chosen for these four
      genes, alone or in combinations, are not statistically significantly associated
      with risk of cigarette-smoking-induced HNSCC.

PMID- 27894335
TI  - Everolimus and exemestane in long survival hormone receptor positive male breast
      cancer: case report.
AB  - BACKGROUND: Male breast cancer is a rare event, accounting for approximately 1%
      of all breast carcinomas. Although men with breast cancer had poorer survival
      when compared with women, data on prognosis principally derive from retrospective
      studies and from extrapolation of female breast cancer series. We reported the
      case of a very long survival patient. CASE PRESENTATION: A caucasian 42-year-old
      man underwent radical mastectomy with axillary dissection for breast cancer in
      1993. Pathologic stage was pT4pN0M0 infiltrating ductal carcinoma of right breast
      without lymph nodes metastases. Biological characterization was not available. He
      received adjuvant treatment with chemotherapy, six cycles of cyclophosphamide,
      methotrexate and fluorouracil, then endocrine therapy with tamoxifen for 5 years
      and complementary radiotherapy. Then he began clinical-instrumental follow up. In
      May 1996, a computed tomography scan showed multiple lung metastases. Hereafter
      he received several oncologic treatment including seven chemotherapy and five
      endocrine therapy lines with two re-challenge of endocrine therapy. In October
      2007 further lung progression was showed and a biopsy was performed to
      characterize the disease. Histological examination confirmed breast cancer
      metastases, immunohistochemistry showed positive staining for estrogen receptor,
      negative for progesterone receptor and human epithelial growth factor receptor 2,
      proliferative index was 21%. In April 2013, bone disease progression was evident
      and he received radiant treatment to sacral spine. In May 2014 an off-label
      treatment with exemestane and everolimus combination was approved by Ethics
      Committee of the Marche Region. The patient received treatment for 3 months with
      evident clinical benefit to subcutaneous lesions of the chest wall that were not
      visible nor palpable on physical examination after 1 month of treatment.
      CONCLUSION: That is the case of long survival male breast cancer patient with
      luminal B subtype and no BRCA mutations. He achieved higher progression free
      survival with endocrine therapy creating the rationale for last line treatment
      with everolimus and exemestane combination. Attending conclusive results from
      ongoing studies, everolimus and exemestane should not be used routinely in male
      metastatic breast cancer patients, but taking into account for selected cases. At
      the best of our knowledge, this is the first case of male beast cancer treated
      with exemestane and everolimus combination.

PMID- 27894338
TI  - Erratum to: Chromatin remodeling factor LSH affects fumarate hydratase as a
      cancer driver.

PMID- 27894337
TI  - Intestinal dysbiosis is common in systemic sclerosis and associated with
      gastrointestinal and extraintestinal features of disease.
AB  - BACKGROUND: Recent evidence suggests a link between autoimmunity and the
      intestinal microbial composition in several rheumatic diseases including systemic
      sclerosis (SSc). The objective of this study was to investigate the prevalence of
      intestinal dysbiosis in SSc and to characterise patients suffering from this
      potentially immunomodulatory deviation. METHODS: This study consisted of 98
      consecutive patients subject to in-hospital care. Stool samples were analysed for
      intestinal microbiota composition using a validated genome-based microbiota test
      (GA-mapTM Dysbiosis Test, Genetic Analysis, Oslo, Norway). Gut microbiota
      dysbiosis was found present as per this standardised test. Patients were examined
      regarding gastrointestinal and extraintestinal manifestations of SSc by clinical,
      laboratory, and radiological measures including esophageal cineradiography, the
      Malnutrition Universal Screening Tool (MUST), levels of plasma transthyretin (a
      marker of malnutrition) and faecal (F-) calprotectin (a marker of intestinal
      inflammation). RESULTS: A majority (75.5%) of the patients exhibited dysbiosis.
      Dysbiosis was more severe (rs = 0.31, p = 0.001) and more common (p = 0.013) in
      patients with esophageal dysmotility. Dysbiosis was also more pronounced in
      patients with abnormal plasma levels of transthyretin (p = 0.045) or
      micronutrient deficiency (p = 0.009). In 19 patients at risk for malnutrition
      according to the MUST, 18 exhibited dysbiosis. Conversely, of the 24 patients
      with a negative dysbiosis test, only one was at risk for malnutrition. The mean
      +/- SEM levels of F-calprotectin were 112 +/- 14 and 45 +/- 8 MUg/g in patients
      with a positive and negative dysbiosis test, respectively. Dysbiosis was more
      severe in patients with skin telangiectasias (p = 0.020), pitting scars (p =
      0.023), pulmonary fibrosis (p = 0.009), and elevated serum markers of
      inflammation (p < 0.001). However, dysbiosis did not correlate with age, disease
      duration, disease subtype, or extent of skin fibrosis. CONCLUSIONS: In this cross
      sectional study, intestinal dysbiosis was common in patients with SSc and was
      associated with gastrointestinal dysfunction, malnutrition and with some
      inflammatory, fibrotic and vascular extraintestinal features of SSc. Further
      studies are needed to elucidate the potential causal relationship of intestinal
      microbe-host interaction in this autoimmune disease.

PMID- 27894336
TI  - Curcumin and long-chain Omega-3 polyunsaturated fatty acids for Prevention of
      type 2 Diabetes (COP-D): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Lifestyle interventions, including increase in physical activity and
      dietary counselling, have shown the ability to prevent type 2 diabetes (T2D) in
      high-risk state individuals, but the prevalence is still skyrocketing in
      Australia, in line with global prevalence. Currently, no medicines are approved
      by the Therapeutic Goods Administration in Australia for the management of
      prediabetes. Therefore, there is a need of developing a safer, biologically
      efficacious and cost-effective alternative for delaying the transition of
      individual health state from prediabetes into T2D. In the current trial we
      propose to evaluate the effects of curcumin and/or long-chain omega-3
      polyunsaturated fatty acids on improving glycosylated haemoglobin as a primary
      outcome, along with secondary outcomes of glycaemic indices, lipid profile and
      inflammatory parameters. METHODS/DESIGN: Eighty individuals diagnosed with
      prediabetes, aged between 30 and 70 years, will be randomly assigned to double
      placebo, curcumin alone, fish oil alone or double active groups according to a
      computer-generated randomisation sequence for 12 weeks. At baseline and post
      intervention visits participants will be asked to provide blood samples and
      undergo body composition measurements. A blood sample is used for estimating
      glycaemic profiles, lipid profiles and inflammatory parameters (C-reactive
      protein, whole blood cell count, adiponectin, leptin, interleukin-6). The interim
      visit includes review on compliance with supplements based on capsule log and
      capsule count, adverse events and anthropometric measurements. In addition to
      these procedures, participants provide self-reported questionnaires on dietary
      intake (using a 3-day food record), a physical activity questionnaire and medical
      history. DISCUSSION: This trial aims to determine whether curcumin and/or long
      chain omega-3 polyunsaturated fatty acids affect surrogate markers of glycaemic
      control which is relevant to delaying T2D. To date 38 participants completed the
      trial. No changes have been made to the clinical protocol post recruitment. If
      successful, this trial will provide considerable evidence for performing a larger
      trial to investigate whether this combination can be administered for preventing
      or delaying the onset of T2D in high-risk individuals. TRIAL REGISTRATION:
      ACTRN12615000559516 , registered on 29 May 2015).

PMID- 27894340
TI  - xHMMER3x2: Utilizing HMMER3's speed and HMMER2's sensitivity and specificity in
      the glocal alignment mode for improved large-scale protein domain annotation.
AB  - BACKGROUND: While the local-mode HMMER3 is notable for its massive speed
      improvement, the slower glocal-mode HMMER2 is more exact for domain annotation by
      enforcing full domain-to-sequence alignments. Since a unit of domain necessarily
      implies a unit of function, local-mode HMMER3 alone remains insufficient for
      precise function annotation tasks. In addition, the incomparable E-values for the
      same domain model by different HMMER builds create difficulty when checking for
      domain annotation consistency on a large-scale basis. RESULTS: In this work, both
      the speed of HMMER3 and glocal-mode alignment of HMMER2 are combined within the
      xHMMER3x2 framework for tackling the large-scale domain annotation task. Briefly,
      HMMER3 is utilized for initial domain detection so that HMMER2 can subsequently
      perform the glocal-mode, sequence-to-full-domain alignments for the detected
      HMMER3 hits. An E-value calibration procedure is required to ensure that the
      search space by HMMER2 is sufficiently replicated by HMMER3. We find that the
      latter is straightforwardly possible for ~80% of the models in the Pfam domain
      library (release 29). However in the case of the remaining ~20% of HMMER3 domain
      models, the respective HMMER2 counterparts are more sensitive. Thus, HMMER3
      searches alone are insufficient to ensure sensitivity and a HMMER2-based search
      needs to be initiated. When tested on the set of UniProt human sequences,
      xHMMER3x2 can be configured to be between 7* and 201* faster than HMMER2, but
      with descending domain detection sensitivity from 99.8 to 95.7% with respect to
      HMMER2 alone; HMMER3's sensitivity was 95.7%. At extremes, xHMMER3x2 is either
      the slow glocal-mode HMMER2 or the fast HMMER3 with glocal-mode. Finally, the E
      values to false-positive rates (FPR) mapping by xHMMER3x2 allows E-values of
      different model builds to be compared, so that any annotation discrepancies in a
      large-scale annotation exercise can be flagged for further examination by
      dissectHMMER. CONCLUSION: The xHMMER3x2 workflow allows large-scale domain
      annotation speed to be drastically improved over HMMER2 without compromising for
      domain-detection with regard to sensitivity and sequence-to-domain alignment
      incompleteness. The xHMMER3x2 code and its webserver (for Pfam release 27, 28 and
      29) are freely available at http://xhmmer3x2.bii.a-star.edu.sg/ . REVIEWERS:
      Reviewed by Thomas Dandekar, L. Aravind, Oliviero Carugo and Shamil Sunyaev. For
      the full reviews, please go to the Reviewers' comments section.

PMID- 27894339
TI  - The identification of human pituitary adenoma-initiating cells.
AB  - Classified as benign central nervous system (CNS) tumors, pituitary adenomas
      account for 10% of diagnosed intracranial neoplasms. Although surgery is often
      curative, patients with invasive macroadenomas continue to experience significant
      morbidity and are prone to tumor recurrence. Given the identification of human
      brain tumor-initiating cells (TICs) that initiate and maintain tumor growth while
      promoting disease progression and relapse in multiple CNS tumors, we investigated
      whether TICs also drive the growth of human pituitary adenomas. Using a
      nanoString-based 80-gene custom codeset specific for developmental pathways, we
      identified a differential stem cell gene expression profile within human
      pituitary adenomas. Prospective functional characterization of stem cell
      properties in patient-derived adenomas representing all hormonal subtypes yielded
      a subtype-dependent self-renewal profile, which was enriched within the CD15+
      cell fraction. The tumor-initiating capacity of CD15high adenoma cells was
      assayed in comparison to CD15low adenomas using in vivo limiting dilutions, which
      maintained the rare frequency of TICs. Repeated analyses using sorted cell
      populations for CD15+ TICs compared to CD15- adenoma cells provided further
      evidence of xenograft tumor formation to support CD15+ cells as putative
      pituitary adenoma-initiating cells (PAICs). The clinical utility of our findings
      was established through in silico analyses and comparative gene expression
      profiling of primary and recurrent pituitary adenomas. CD15 was enriched in
      recurrent adenomas, which was validated using routine clinical
      immunohistochemistry in a limited number of samples. Our work reports the first
      prospective identification of human PAICs using CD15. Patients with CD15high
      adenomas may therefore benefit from more aggressive surgical interventions and
      chemo/radiotherapy.

PMID- 27894341
TI  - Abdominal obesity, gender and the risk of rheumatoid arthritis - a nested case
      control study.
AB  - BACKGROUND: The risk of development of rheumatoid arthritis (RA) could be
      affected by immune activation in obesity. Our objective was to evaluate the
      association between obesity in general, and abdominal obesity, and the risk for
      subsequent development of RA. METHODS: In two large population-based, prospective
      cohorts, 557 cases (mean age at RA symptom onset 58, SD 10 years, 68% women) who
      subsequently developed RA and 1671 matched controls were identified. From a
      health examination antedating symptom onset (median 5.5 years), collected data on
      body mass index (BMI; kg/m2), smoking habits, and educational level was used in
      conditional logistical regression models. Corresponding regression models were
      used to analyse the association between waist circumference measurements (cm) and
      RA development in a subset of the population. RESULTS: BMI and waist
      circumference were associated with the risk of RA development, adjusted odds
      ratio (OR) (95% CI), 1.13 (1.00, 1.28) per 5 kg/m2, and 1.02 (1.01, 1.04) per cm,
      respectively. An association was also observed for obesity (BMI >=30) OR 1.45
      (1.07, 1.95), compared with BMI <25. After stratification for sex the
      associations were enhanced in men, and attenuated in women. Among men with BMI
      above normal a 3-5 times increased risk for RA disease development at 50 years of
      age or earlier was observed. Abdominal obesity with waist circumference >102 cm
      was associated with a 2-3 times increased risk of RA, but not abdominal obesity
      (>88 cm) in women. CONCLUSIONS: Obesity or abdominal obesity, respectively, was
      independently associated with a modest increase of the risk for subsequent
      development of RA. This appeared to be relevant mainly for early RA disease onset
      among men.

PMID- 27894342
TI  - Inequalities in the spiritual health of young Canadians: a national, cross
      sectional study.
AB  - BACKGROUND: Spiritual health, along with physical, emotional, and social aspects,
      is one of four domains of health. Assessment in this field of research is
      challenging methodologically. No contemporary population-based studies have
      profiled the spiritual health of adolescent Canadians with a focus on health
      inequalities. In a 2014 nationally representative sample of Canadians aged 11-15
      years we therefore: (1) psychometrically evaluated a series of items used to
      assess the perceived importance of spiritual health and its four potential sub
      domains (connections with: self, others, nature and the natural environment, and
      the transcendent) to adolescents; (2) described potential inequalities in
      spiritual health within adolescent populations, overall and by spiritual health
      sub-domain, by key socio-demographic factors. METHODS: Cross-sectional analysis
      of survey reports from the 2014 (Cycle 7) of the Canadian Health Behaviour in
      School-aged Children study (weighted n = 25,036). Principal components analysis
      followed by confirmatory factor analysis were used to explore the psychometric
      properties of the spiritual health items and the associated composite scale
      describing perceived importance of spiritual health. Associations among this
      composite scale, its individual sub-domains, and key socio-demographic factors
      were then explored. RESULTS: The principal components analysis best supported a
      four-factor structure where the eight scale items loaded highly according to the
      original four domains. This was also supported in confirmatory factor analyses.
      We then combined the eight items into composite spiritual health score as
      supported by theory, principal components analysis findings, and acceptable tests
      of reliability. Further confirmatory factor analysis suggested the need for
      additional refinements to this scale. Based upon exploratory cross-sectional
      analyses, strong socio-demographic inequalities were observed in the spiritual
      health measures by age, gender, relative material wealth, immigration status, and
      province/territory. CONCLUSIONS: Study findings highlight potential inequalities
      in the spiritual health of young Canadians, as well as opportunities for
      methodological advances in the assessment of adolescent spiritual health in our
      population.

PMID- 27894343
TI  - Post-marketing withdrawal of anti-obesity medicinal products because of adverse
      drug reactions: a systematic review.
AB  - BACKGROUND: We identified anti-obesity medications withdrawn since 1950 because
      of adverse drug reactions after regulatory approval, and examined the evidence
      used to support such withdrawals, investigated the mechanisms of the adverse
      reactions, and explored the trends over time. METHODS: We conducted searches in
      PubMed, the World Health Organization database of drugs, the websites of drug
      regulatory authorities, and selected full texts, and we hand searched references
      in retrieved documents. We included anti-obesity medications that were withdrawn
      between 1950 and December 2015 and assessed the levels of evidence used for
      making withdrawal decisions using the Oxford Centre for Evidence-Based Medicine
      criteria. RESULTS: We identified 25 anti-obesity medications withdrawn between
      1964 and 2009; 23 of these were centrally acting, via monoamine
      neurotransmitters. Case reports were cited as evidence for withdrawal in 80% of
      instances. Psychiatric disturbances, cardiotoxicity (mainly attributable to re
      uptake inhibitors), and drug abuse or dependence (mainly attributable to
      neurotransmitter releasing agents) together accounted for 83% of withdrawals.
      Deaths were reportedly associated with seven products (28%). In almost half of
      the cases, the withdrawals occurred within 2 years of the first report of an
      adverse reaction. CONCLUSIONS: Most of the drugs that affect monoamine
      neurotransmitters licensed for the treatment of obesity over the past 65 years
      have been withdrawn because of adverse reactions. The reasons for withdrawal
      raise concerns about the wisdom of using pharmacological agents that target
      monoamine neurotransmitters in managing obesity. Greater transparency in the
      assessment of harms from anti-obesity medications is therefore warranted.

PMID- 27894345
TI  - Ultrasonographic features of adrenal gland lesions in dogs can aid in diagnosis.
AB  - BACKGROUND: Ultrasonography to visualize adrenal gland lesions and evaluate
      incidentally discovered adrenal masses in dogs has become more reliable with
      advances in imaging techniques. However, correlations between sonographic and
      histopathological changes have been elusive. The goal of our study was to
      investigate which ultrasound features of adrenal gland abnormalities could aid in
      discriminating between benign and malignant lesions. To this end, we compared
      diagnosis based on ultrasound appearance and histological findings and evaluated
      ultrasound criteria for predicting malignancy. RESULTS: Clinical records of 119
      dogs that had undergone ultrasound adrenal gland and histological examination
      were reviewed. Of these, 50 dogs had normal adrenal glands whereas 69 showed
      pathological ones. Lesions based on histology were classified as cortical adrenal
      hyperplasia (n = 67), adenocarcinoma (n = 17), pheochromocytoma (n = 10),
      metastases (n = 7), adrenal adenoma (n = 4), and adrenalitis (n = 4).
      Ultrasonographic examination showed high specificity (100%) but low sensitivity
      (63.7%) for identifying the adrenal lesions, which improved with increasing
      lesion size. Analysis of ultrasonographic predictive parameters showed a
      significant association between lesion size and malignant tumors. All adrenal
      gland lesions >20 mm in diameter were histologically confirmed as malignant
      neoplasms (pheochromocytoma and adenocarcinoma). Vascular invasion was a specific
      but not sensitive predictor of malignancy. As nodular shape was associated with
      benign lesions and irregular enlargement with malignant ones, this parameter
      could be used as diagnostic tool. Bilaterality of adrenal lesions was a useful
      ultrasonographic criterion for predicting benign lesions, as cortical
      hyperplasia. CONCLUSIONS: Abnormal appearance of structural features on
      ultrasound images (e.g., adrenal gland lesion size, shape, laterality, and
      echotexture) may aid in diagnosis, but these features alone were not pathognomic.
      Lesion size was the most direct ultrasound predictive criterion. Large and
      irregular masses seemed to be better predictors of malignant neoplasia and
      lesions <20 mm in diameter and nodular in shape were often identified as cortical
      hyperplastic nodules or adenomas.

PMID- 27894344
TI  - Siropins, novel serine protease inhibitors from gut microbiota acting on human
      proteases involved in inflammatory bowel diseases.
AB  - BACKGROUND: In eukaryotes, the serpins constitute a wide family of protease
      inhibitors regulating many physiological pathways. Many reports stressed the key
      role of serpins in several human physiopathologies including mainly the
      inflammatory bowel diseases. In this context, eukaryotic serpins were largely
      studied and their use to limit inflammation was reported. In comparison to that,
      bacterial serpins and mainly those from human gut microbiota remain poorly
      studied. RESULTS: The two genes encoding for putative serpins from the human gut
      bacterium Eubacterium sireaum, display low sequence identities. These genes were
      overexpressed and the encoded proteins, named Siropins, were purified. Activity
      studies demonstrated that both purified proteins inhibited serine proteases but
      surprisingly they preferentially inhibited two human serine proteases (Human
      Neutrophil Elastase and Proteinase3). The biochemical characterization of these
      Siropins revealed that Siropin 1 was the most active and stable at low pH values
      while Siropin 2 was more thermoactive and thermostable. Kinetic analysis allowed
      the determination of the stoichiometry of inhibition (SI) which was around 1 and
      of the association rate constants of 7.7 * 104 for the Human Neutrophil Elastase
      and 2.6 * 105 for the Proteinase3. Moreover, both Siropins displayed the ability
      to inhibit proteases usually present in fecal waters. Altogether our data
      indicate the high efficiency of Siropins and their probable involvement in the
      control of the overall intestine protease activity. CONCLUSIONS: Here we report
      the purification and the biochemical characterization of two novel serpins
      originated from Eubacterium sireaum, a human gastro-intestinal tract commensal
      bacteria. These proteins that we called Siropins, efficiently inhibited two human
      proteases reported to be associated with inflammatory bowel diseases. The
      determination of the biochemical properties of these enzymes revealed different
      temperature and pH behaviours that may reflect adaptation of this human commensal
      bacterium to different ecological environments. To the best of our knowledge, it
      is the first bacterial serpins showing an attractive inhibition of fecal
      proteases recovered from a mice group with chemically induced inflammation.
      Altogether our data highlight the interesting potential of Siropins, and serpins
      from the human gut microbiota in general, to be used as new alternative to face
      inflammatory diseases.

PMID- 27894346
TI  - A retrospective review of birth outcomes at the Mother and Child Health Hospital
      in Lao People's Democratic Republic, 2004-2013.
AB  - BACKGROUND: The Lao People's Democratic Republic (Lao PDR) is a lower-middle
      income country making steady progress improving maternal and child health
      outcomes. We sought to ascertain if there have been improvements in three
      specific birth outcomes (low birth weight, preterm birth and small for
      gestational age) over the last decade. METHODS: We retrospectively reviewed birth
      records between 2004 and 2013 at the Mother and Child Health (MCH) hospital in
      Vientiane. We defined preterm birth as gestation <37 weeks and low birth weight
      as <2,500 g. We calculated small for gestational age (SGA). We describe birth
      outcomes over time and compare proportions using Chi square. RESULTS: Between
      2004 and 2013, the annual average number of newborns delivered each year was
      4,322 and the frequency of low birth weight ranged from 9.5 to 12%, preterm
      births from 6.3 to 10%, and infants born SGA from 25 to 35%. There were no
      improvements in these frequencies over time. Women <18 years at delivery had a
      statistically significantly higher frequency of babies born with a low birth
      weight (15.3 vs. 10.8%, p < 0.02) or preterm (16.4 vs. 7.8%, p < 0.01) than those
      aged >18. There was no difference in the frequency of babies born SGA by age
      (26.8% in women <18 years vs. 29.7% in women >18 years, p = 0.30). CONCLUSIONS:
      At the largest maternal and child hospital in Lao PDR, we found a high frequency
      of poor birth outcomes with no improvements over the last decade.

PMID- 27894347
TI  - Estimation of utility weights for human papilloma virus-related health states
      according to disease severity.
AB  - BACKGROUND: A cost-utility study of a human papilloma virus (HPV) vaccine
      requires that the utility weights for HPV-related health states (i.e., cervical
      intraepithelial neoplasia (CIN), cervical cancer, and condyloma) be evaluated.
      The aim of the present study was to determine the utility weights for HPV-related
      health states. METHODS: Hypothetical standardised health states related to HPV
      were developed based on patient education material and previous publications. To
      fully reflect disease progression from diagnosis to prognosis, each health state
      comprised four parts (diagnosis, symptoms, treatment, and progression and
      prognosis). Nine-hundred members from the Korean general population evaluated the
      HPV-related health states using a visual analogue scale (VAS) and a standard
      gamble (SG) approach, which were administered face-to-face via computer-assisted
      interview. The mean utility values were calculated for each HPV-related health
      state. RESULTS: According to the VAS, the highest utility (0.73) was HPV-positive
      status, followed by condyloma (0.66), and CIN grade I (0.61). The lowest utility
      (0.18) was cervical cancer requiring chemotherapy without surgery, followed by
      cervical cancer requiring chemoradiation therapy (0.42). SG revealed that the
      highest utility (0.83) was HPV-positive status, followed by condyloma (0.78), and
      CIN grade I (0.77). The lowest utility (0.43) was cervical cancer requiring
      chemotherapy without surgery, followed by cervical cancer requiring
      chemoradiation therapy (0.60). CONCLUSIONS: This study was based on a large
      sample derived from the general Korean population; therefore, the calculated
      utility weights might be useful for evaluating the economic benefit of cancer
      screening and HPV vaccination programs.

PMID- 27894348
TI  - Change in luminal diameter of the left internal thoracic artery anastomosed to
      the totally occluded left anterior descending coronary artery.
AB  - BACKGROUND: Coronary artery bypass grafting (CABG) with a composite Y-graft made
      of the left internal thoracic artery (LITA) and another arterial graft has a risk
      for hypoperfusion. Changes over time in the diameter of the LITA anastomosed to
      the left anterior descending coronary artery (LAD) are not known. METHODS: Data
      were collected for 71 patients who had undergone coronary angiography (CAG)
      immediately and at 1 year following off-pump CABG with a composite Y-graft made
      of the LITA and either the radial artery or the right gastroepiploic artery.
      These patients were divided into 2 groups depending on the degree of LAD
      stenosis. Group 1 (n = 28) consisted of patients with complete occlusion of the
      LAD. Group 2 (n = 43) consisted of patients with <90% stenosis of the LAD. The
      clinical state and luminal diameter of the LITA on immediate postoperative and
      postoperative 1-year CAG were compared and analyzed. RESULTS: On the immediate
      postoperative CAG, mean LITA diameter of Group 1 was larger than that of Group 2
      (2.09 +/- 0.53 vs. 1.61 +/- 0.33 mm, P = 0.01). Mean LITA diameter 1 year
      following CABG was also larger in Group 1 than in Group 2 (2.49 +/- 0.31 vs. 2.10
      +/- 0.45 mm, P = 0.005). Both groups showed significant increases in the LITA
      diameters at postoperative 1 year. CONCLUSIONS: The LITA used as a composite Y
      graft underwent remodeling, resulting in a larger diameter, to supply adequate
      myocardial blood. The degree of change in luminal diameter varied according to
      the severity of the LAD stenosis.

PMID- 27894349
TI  - "When I saw walking I just kind of took it as wheeling": interpretations of
      mobility-related items in generic, preference-based health state instruments in
      the context of spinal cord injury.
AB  - BACKGROUND: In health economic analyses, health states are typically valued using
      instruments with few items per dimension. Due to the generic (and often
      reductionist) nature of such instruments, certain groups of respondents may
      experience challenges in describing their health state. This study is concerned
      with generic, preference-based health state instruments that provide information
      for decisions about the allocation of resources in health care. Unlike physical
      measurement instruments, preference-based health state instruments provide health
      state values that are dependent on how respondents interpret the items. This
      study investigates how individuals with spinal cord injury (SCI) interpret
      mobility-related items contained within six preference-based health state
      instruments. METHODS: Secondary analysis of focus group transcripts originally
      collected in Vancouver, Canada, explored individuals' perceptions and
      interpretations of mobility-related items contained within the 15D, Assessment of
      Quality of Life 8-dimension (AQoL-8D), EQ-5D-5L, Health Utilities Index (HUI),
      Quality of Well-Being Scale Self-Administered (QWB-SA), and the 36-item Short
      Form health survey version 2 (SF-36v2). Ritchie and Spencer's 'Framework
      Approach' was used to perform thematic analysis that focused on participants'
      comments concerning the mobility-related items only. RESULTS: Fifteen individuals
      participated in three focus groups (five per focus group). Four themes emerged:
      wording of mobility (e.g., 'getting around' vs 'walking'), reference to aids and
      appliances, lack of suitable response options, and reframing of items (e.g.,
      replacing 'walking' with 'wheeling'). These themes reflected item features that
      respondents perceived as relevant in enabling them to describe their mobility,
      and response strategies that respondents could use when faced with inaccessible
      items. CONCLUSION: Investigating perceptions to mobility-related items within the
      context of SCI highlights substantial variation in item interpretation across six
      preference-based health state instruments. Studying respondents' interpretations
      of items can help to understand discrepancies in the health state descriptions
      and values obtained from different instruments. This line of research warrants
      closer attention in the health economics and quality of life literature.

PMID- 27894350
TI  - GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment.
AB  - BACKGROUND: The aim of this study was to investigate the effect of downregulating
      Hedgehog pathway by GANT61 on human glioma cells, examine the consequent changes
      of temozolomide (TMZ)-induced effects and explore the molecular mechanisms.
      METHODS: The cytotoxicity of a Gli1/2 inhibitor, GANT61 was examined both alone
      and in combination with TMZ in human glioma cell lines. The mRNA and protein
      expression alterations were determined by quantitative real-time polymerase chain
      reaction (qRT-PCR) and Western blot, respectively. CCK-8 assay detected the cell
      proliferative capability. Apoptotic cell number was measured by flow cytometry.
      The transwell assay was used to test the cell invasive capability. DNA damage
      effect was identified by COMET assay and gammaH2AX expression. RESULTS:
      Proliferation of tumor cells treated with GANT61 in combination with TMZ was
      significantly suppressed compared with those treated with either drug used alone.
      The combination treatment induced a higher rate of apoptosis, DNA damage and
      reduced the invasive capability of glioma cells. DNA damage repair enzyme MGMT
      and the Notch1 pathway increased in the cells treated by TMZ treatment. However,
      GANT61 could abrogated the protein increasing. CONCLUSIONS: GANT61 sensitizes
      glioma cells to TMZ treatment by enhancing DNA damage effect, decreasing MGMT
      expression and the Notch1 pathway.

PMID- 27894352
TI  - Immunoassay of S-adenosylmethionine and S-adenosylhomocysteine: the methylation
      index as a biomarker for disease and health status.
AB  - BACKGROUND: S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are
      relevant to a variety of diseases. Previous reports that quantified SAM and SAH
      were based on HPLC or LC-MS/MS. No antibody against SAM has been generated, and
      the antibody against SAH cannot be used with blood samples. Immunoassays have not
      been used to measure SAM and SAH. In this study, ELISA was used to measure blood
      SAM and SAH levels. RESULTS: Specific antibodies against SAM were produced for
      the first time using a stable analog as the antigen. The monoclonal antibodies
      against SAM and SAH were characterized. No cross-reactivity was detected for the
      analyzed analogs. For the anti-SAM antibodies, the ELISA sensitivity was ~2 nM,
      and the affinity was 7.29 * 1010 L/mol. For the anti-SAH antibodies, the
      sensitivity was ~15 nM, and the affinity was 2.79 * 108 L/mol. Using high-quality
      antibodies against SAM and SAH, immunoassays for the detection of SAM and SAH
      levels in blood and tissue samples were developed. Clinical investigations using
      immunoassays to measure SAM, SAH and the methylation index (MI) in normal and
      diseased samples indicated that (1) the SAM level is age and gender dependent;
      (2) the SAM level is associated with the severity of liver diseases, inflammatory
      reactions and other diseases; and (3) the methylation index (MI) is significantly
      reduced in many diseases and may serve as a screening biomarker to identify
      potentially unfavorable health conditions. CONCLUSION: It is possible to generate
      antibodies against active small biomolecules with weak immunogenicity, such as
      SAM and SAH, using traditional hybridoma technology. The antigens and antibodies
      described here will contribute to the development of immunoassays to measure SAM,
      SAH and related molecules. These assays enable the MI to be measured
      specifically, accurately, easily and quickly without costly equipment. This
      preliminary study indicates that the MI could be an effective indicator of
      general health, except under conditions that may alter the value of the MI, such
      as special diets and medications.

PMID- 27894351
TI  - Characterizing the morbid genome of ciliopathies.
AB  - BACKGROUND: Ciliopathies are clinically diverse disorders of the primary cilium.
      Remarkable progress has been made in understanding the molecular basis of these
      genetically heterogeneous conditions; however, our knowledge of their morbid
      genome, pleiotropy, and variable expressivity remains incomplete. RESULTS: We
      applied genomic approaches on a large patient cohort of 371 affected individuals
      from 265 families, with phenotypes that span the entire ciliopathy spectrum.
      Likely causal mutations in previously described ciliopathy genes were identified
      in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a
      fully penetrant model for these genes, we found no significant difference in
      their "mutation load" beyond the causal variants between our ciliopathy cohort
      and a control non-ciliopathy cohort. Genomic analysis of our cohort further
      identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase,
      based on independent loss of function mutations in individuals with a consistent
      ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its
      deficiency on ciliary signaling. Our study also highlighted seven novel candidate
      genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of
      which have established links to ciliogenesis. Finally, we show that the morbid
      genome of ciliopathies encompasses many founder mutations, the combined carrier
      frequency of which accounts for a high disease burden in the study population.
      CONCLUSIONS: Our study increases our understanding of the morbid genome of
      ciliopathies. We also provide the strongest evidence, to date, in support of the
      classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies.

PMID- 27894353
TI  - Provider and user acceptability of intermittent screening and treatment for the
      control of malaria in pregnancy in Malawi.
AB  - BACKGROUND: Malaria in pregnancy is a major cause of adverse maternal and fetal
      outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp
      SP) is one of the control strategies promoted by WHO. In response to mounting
      resistance to SP, intermittent screening and treatment (ISTp) has been proposed
      as an alternative. The objective of this study was to explore the acceptability
      of ISTp for health workers and pregnant women. METHODS: Semi-structured
      interviews of ten health workers and five focus group discussions of 38 women
      enrolled in an ongoing trial comparing IPTp-SP and ISTp with dihydroartemisinin
      piperaquine (DP) were conducted at two antenatal clinics in rural Malawi. All
      transcripts were coded and themes were identified using a content analysis
      approach. RESULTS: Amongst health workers, there were contrasting opinions on the
      preference of blood sampling methods, and the influence of method on reliability
      of diagnosis. The perceived greater effectiveness of DP compared to SP was
      appreciated, however concerns of user compliance with the full dose of DP in non
      trial settings were raised. Despite the discomfort of repeated finger pricks,
      pregnant women were generally accepting of ISTp, particularly the chance for
      regular blood tests to check for infections and the perceived greater
      effectiveness with fewer side effects of DP compared to SP. CONCLUSION: In the
      trial context, pregnant women tended to prefer ISTp-DP over IPTp-SP. Health
      workers were also accepting of ISTp-DP as an alternative to IPTp-SP in light of
      increasing SP resistance. However, reliability of stock, adherence to malaria
      test results and user adherence to the full course of DP may present barriers to
      successful routine implementation. Effective communication with health workers
      and between health workers, pregnant women and their communities will be
      essential for the acceptability of focused antenatal care, including the best
      malaria control measures available.

PMID- 27894354
TI  - Do mosquitoes transmit the avian malaria-like parasite Haemoproteus? An
      experimental test of vector competence using mosquito saliva.
AB  - BACKGROUND: The life-cycle of many vector-borne pathogens includes an asexual
      replication phase in the vertebrate host and sexual reproduction in the insect
      vector. However, as only a small array of parasites can successfully develop
      infective phases inside an insect, few insect species are competent vectors for
      these pathogens. Molecular approaches have identified the potential insect
      vectors of blood parasites under natural conditions. However, the effectiveness
      of this methodology for verifying mosquito competence in the transmission of
      avian malaria parasites and related haemosporidians is still under debate. This
      is mainly because positive amplifications of parasite DNA in mosquitoes can be
      obtained not only from sporozoites, the infective phase of the malaria parasites
      that migrate to salivary glands, but also from different non-infective parasite
      forms in the body of the vector. Here, we assessed the vectorial capacity of the
      common mosquito Culex pipiens in the transmission of two parasite genera.
      METHODS: A total of 1,560 mosquitoes were allowed to feed on five house sparrows
      Passer domesticus naturally infected by Haemoproteus or co-infected by
      Haemoproteus/Plasmodium. A saliva sample of the mosquitoes that survived after 13
      days post-exposure was taken to determine the presence of parasite DNA by PCR.
      RESULTS: Overall, 31.2% mosquito's head-thorax and 5.8% saliva samples analysed
      showed positive amplifications for avian malaria parasites. In contrast to
      Haemoproteus DNA, which was not found in either the body parts or the saliva,
      Plasmodium DNA was detected in both the head-thorax and the saliva of mosquitoes.
      Parasites isolated from mosquitoes feeding on the same bird corresponded to the
      same Plasmodium lineage. CONCLUSIONS: Our experiment provides good evidence for
      the competence of Cx. pipiens in the transmission of Plasmodium but not of
      Haemoproteus. Molecular analyses of saliva are an effective method for testing
      the vector competence of mosquitoes and other insects in the transmission of
      vector-borne pathogens.

PMID- 27894355
TI  - Generation of mAbs to foot-and-mouth disease virus serotype A and application in
      a competitive ELISA for serodiagnosis.
AB  - BACKGROUND: Foot-and-mouth disease (FMD) is an economically devastating disease
      that severely limits international trade of animals. Of the seven FMD virus
      (FMDV) serotypes, serotype A is one of the most widespread cross the world.
      Currently antibodies to FMDV are detected in animals using the virus
      neutralization test (VNT) and the enzyme-linked immunosorbent assay (ELISA). The
      VNT is laborious, time-consuming and reliant on live virus and cell cultures,
      while ELISA has the advantage of using inactivated antigens and often provides
      more reproducible results. The aim of this study was to develop a reliable and
      rapid competitive ELISA (cELISA) for the detection of antibodies to FMDV serotype
      A (FMDV/A). RESULTS: A panel of FMDV/A specific monoclonal antibodies (mAbs) was
      generated and their ability to compete with a polyclonal serum from FMDV/A
      infected cattle was examined. Two mAbs inhibited the binding of a polyclonal
      serum to FMDV/A viruses. The binding epitopes of each were determined as
      conformational and located on the VP2 viral capsid protein. The FMDV/A cELISA was
      developed using these two mAbs and FMDV/A inactivated virus as antigen. The
      diagnostic specificity and sensitivity were 99.7 and 99.3% (98.5-100%)
      respectively, based on a predetermined cut-off of 50% inhibition. When analysing
      sera from animals experimentally infected with FMDV/A, the cELISA detected
      antibodies from 5-days post infection (dpi) and remained positive for at least 21
      28 days post infection. Comparison based on the Kappa coefficient showed strong
      agreement (90-94%) between cELISA and VNT. CONCLUSION: The cELISA results are
      comparable to the VNT for antibody detection making it a simple and reliable test
      to detect antibodies against FMDV/A.

PMID- 27894356
TI  - Transmission of Calicophoron daubneyi and Fasciola hepatica in Galicia (Spain):
      Temporal follow-up in the intermediate and definitive hosts.
AB  - BACKGROUND: Paramphistomosis caused by Calicophoron daubneyi and fasciolosis
      caused by Fasciola hepatica are common parasitic diseases of livestock animals.
      Transmission of the diseases depends on the presence of intermediate hosts, i.e.
      freshwater gastropods such as lymnaeids. We carried out a 2-year-long study of
      the dynamics of the snail population acting as the intermediate host for these
      parasites, considering the population structure in terms of size/age and
      infection status. In addition, we determined the kinetics of trematode egg
      excretion in grazing cows. Generalized Additive Models (GAMs) were used to
      analyze the associations between different response variables and snail size,
      sampling month and weather-related variables. RESULTS: Of the molluscan species
      examined, Galba truncatula, Radix peregra, Anisus (Anisus) leucostoma and
      Pisidium casertanum (n = 2802), only G. truncatula was infected with C. daubneyi
      or F. hepatica, at prevalence rates of 8.2% and 4.4% respectively. The
      probability of infection with C. daubneyi or F. hepatica was linearly related to
      snail size, although in different ways (negative for C. daubneyi and positive for
      F. hepatica). The total snail population increased in winter, when specimens of
      all size classes were found. Infected snails were more abundant during spring
      autumn. Mature cercariae of both parasites were found in most seasons. In the
      statistical models, the sampling month accounted for a high percentage (71.9
      78.2%) of the observed variability in snail abundance. The inclusion of climatic
      variables in the models moderately increased the percentage of deviance explained
      (77.7-91.9%). Excretion of C. daubneyi eggs in cow faeces was always higher than
      that of F. hepatica eggs. CONCLUSIONS: Particular care should be taken to prevent
      pastures and the surrounding environment being contaminated with parasite eggs
      during winter-spring, when the number of snails susceptible to miracidial
      infections is maximal. This is therefore the optimal time for treating grazing
      animals. Nevertheless, control of trematodosis based only on chemotherapy is
      difficult in an area such as the study area, where environmental factors favour
      the regular appearance of snail populations harbouring mature cercariae.

PMID- 27894358
TI  - Attentional and affective consequences of technology supported mindfulness
      training: a randomised, active control, efficacy trial.
AB  - BACKGROUND: Mindfulness training (MT) programs represent an approach to attention
      training with well-validated mental health benefits. However, research supporting
      MT efficacy is based predominantly on weekly-meeting, facilitator-led, group
      intervention formats. It is unknown whether participants might benefit from
      neurofeedback-assisted, technology-supported MT (N-tsMT), in which meditation is
      delivered individually, without the need for a facilitator, travel to a training
      site, or the presence of a supportive group environment. Mirroring the validation
      of group MT interventions, the first step in addressing this question requires
      identifying whether N-tsMT promotes measurable benefits. Here, we report on an
      initial investigation of a commercial N-tsMT system. METHODS: In a randomized,
      active control trial, community-dwelling healthy adult participants carried out 6
      weeks of daily practice, receiving either N-tsMT (n = 13), or a control condition
      of daily online math training (n = 13). Training effects were assessed on target
      measures of attention and well-being. Participants also completed daily post
      training surveys assessing effects on mood, body awareness, calm, effort, and
      stress. RESULTS: Analysis revealed training effects specific to N-tsMT, with
      attentional improvements in overall reaction time on a Stroop task, and well
      being improvements via reduced somatic symptoms on the Brief Symptom Inventory.
      Attention and well-being improvements were correlated, and effects were greatest
      for the most neurotic participants. However, secondary, exploratory measures of
      attention and well-being did not show training-specific effects. N-tsMT was
      associated with greater body awareness and calm, and initially greater effort
      that later converged with effort in the control condition. CONCLUSIONS:
      Preliminary findings indicate that N-tsMT promotes modest benefits for attention
      and subjective well-being in a healthy community sample relative to an active
      control condition. However, the findings would benefit from replication in a
      larger sample, and more intensive practice or more comprehensive MT instruction
      might be required to promote the broader benefits typically reported in group
      format, facilitated MT. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN43629398 . Retrospectively registered on June 16, 2016.

PMID- 27894361
TI  - Non-human Primate Malaria Parasites: out of the forest and into the laboratory -
      CORRIGENDUM.

PMID- 27894360
TI  - The relationship of endotoxaemia to peripheral and central nervous system
      inflammatory responses in Human African Trypanosomiasis.
AB  - Endotoxaemia has been described in cases of Human African trypanosomiasis (HAT),
      but it is unclear if this phenomenon influences inflammatory pathology either in
      the periphery or central nervous system (CNS). We studied endotoxin
      concentrations in the plasma and cerebrospinal fluid (CSF) of Trypanosoma brucei
      rhodesiense patients using the chromogenic Limulus Amoebocyte lysate assay. The
      relationship of endotoxin concentration to the presentation of gross signs of
      inflammation and the inflammatory/counter-inflammatory cytokine profile of the
      relevant compartments were analysed. We demonstrate that HAT patients exhibit
      parasitaemia-independent plasma endotoxaemia, and that this is associated with
      splenomegaly and lymphadenopathy. Endotoxin concentrations normalize rapidly
      after treatment. There was no evidence of endotoxin release in the CNS. A rapid
      normalization of endotoxin levels after treatment and lack of association with
      parasitaemia suggest that gut leakage is the main source of endotoxin in the
      circulation. Low CSF endotoxin concentrations and a lack of any association with
      neuroinflammatory markers or neurological sequelae suggest that endotoxin does
      not play a role in the pathogenesis of the disease in the CNS.

PMID- 27894359
TI  - Can morphological MRI differentiate between primary central nervous system
      lymphoma and glioblastoma?
AB  - BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive
      brain neoplasm that accounts for roughly 2-6% of primary brain tumors. In
      contrast, glioblastoma (GBM) is the most frequent and severe glioma subtype,
      accounting for approximately 50% of diffuse gliomas. The aim of the present study
      was to evaluate morphological MRI characteristics in histologically-proven PCNSL
      and GBM at the time of their initial presentation. METHODS: We retrospectively
      evaluated standard diagnostic MRI examinations in 54 immunocompetent patients (26
      female, 28 male; age 62.6 +/- 11.5 years) with histologically-proven PCNSL and 54
      GBM subjects (21 female, 33 male; age 59 +/- 14 years). RESULTS: Several
      significant differences between both infiltrative brain tumors were found. PCNSL
      lesions enhanced homogenously in 64.8% of cases, while nonhomogeneous enhancement
      was observed in 98.1% of GBM cases. Necrosis was present in 88.9% of GBM lesions
      and only 5.6% of PCNSL lesions. PCNSL presented as multiple lesions in 51.9%
      cases and in 35.2% of GBM cases; however, diffuse infiltrative type of brain
      involvement was observed only in PCNSL (24.1%). Optic pathways were infiltrated
      more commonly in PCNSL than in GBM (42.6% vs. 5.6%, respectively, p <0.001).
      Other cranial nerves were affected in 5.6% of PCNSL, and in none of GBM. Signs of
      bleeding were rare in PCNSL (5.6%) and common in GBM (44.4%); p < 0.001. Both
      supratentorial and infratentorial localization was present only in PCNSL (27.7%).
      Involvement of the basal ganglia was more common in PCNSL (55.6%) than in GBM
      (18.5%); (p < 0.001). Cerebral cortex was affected significantly more often in
      GBM (83.3%) than in PCNSL (51.9%); mostly by both enhancing and non-enhancing
      infiltration. CONCLUSION: Routine morphological MRI is capable of differentiating
      between GBM and PCNSL lesions in many cases at time of initial presentation. A
      solitary infiltrative supratentorial lesion with nonhomogeneous enhancement and
      necrosis was typical for GBM. PCNSL presented with multiple lesions that enhanced
      homogenously or as diffuse infiltrative type of brain involvement, often with
      basal ganglia and optic pathways affection.

PMID- 27894362
TI  - The trypanosome alternative oxidase: a potential drug target?
AB  - New drugs against Trypanosoma brucei, the causative agent of Human African
      Trypanosomiasis, are urgently needed to replace the highly toxic and largely
      ineffective therapies currently used. The trypanosome alternative oxidase (TAO)
      is an essential and unique mitochondrial protein in these parasites and is absent
      from mammalian mitochondria, making it an attractive drug target. The structure
      and function of the protein are now well characterized, with several inhibitors
      reported in the literature, which show potential as clinical drug candidates. In
      this review, we provide an update on the functional activity and structural
      aspects of TAO. We then discuss TAO inhibitors reported to date, problems
      encountered with in vivo testing of these compounds, and discuss the future of
      TAO as a therapeutic target.

PMID- 27894363
TI  - Vector species richness increases haemorrhagic disease prevalence through
      functional diversity modulating the duration of seasonal transmission - ERRATUM.

PMID- 27894357
TI  - New insights into the generation and role of de novo mutations in health and
      disease.
AB  - Aside from inheriting half of the genome of each of our parents, we are born with
      a small number of novel mutations that occurred during gametogenesis and
      postzygotically. Recent genome and exome sequencing studies of parent-offspring
      trios have provided the first insights into the number and distribution of these
      de novo mutations in health and disease, pointing to risk factors that increase
      their number in the offspring. De novo mutations have been shown to be a major
      cause of severe early-onset genetic disorders such as intellectual disability,
      autism spectrum disorder, and other developmental diseases. In fact, the
      occurrence of novel mutations in each generation explains why these
      reproductively lethal disorders continue to occur in our population. Recent
      studies have also shown that de novo mutations are predominantly of paternal
      origin and that their number increases with advanced paternal age. Here, we
      review the recent literature on de novo mutations, covering their detection,
      biological characterization, and medical impact.

PMID- 27894364
TI  - The changing landscape of oropharyngeal cancer management.
AB  - BACKGROUND: Oropharyngeal cancer is increasing in prevalence in the UK and this
      is thought to be due to the emergence of disease related to human papilloma
      virus. METHOD: A literature review was conducted on the diagnosis and latest
      management of oropharyngeal cancer. RESULTS: In non-smokers, human papilloma
      virus related disease is thought to have better outcomes, but this casts doubt on
      previous research which did not stratify patients according to human papilloma
      virus status. However, this theory provides a route for researchers to risk
      stratify and de-escalate treatments, and hence reduce treatment burden. In
      addition, the emergence of minimally invasive transoral techniques allows
      surgeons to remove large tumours without many of the side effects associated with
      radical (chemo)radiotherapy. CONCLUSION: The emergence of human papilloma virus
      related disease and minimally invasive techniques have led the clinical and
      academic community to reconsider how oropharyngeal cancer is managed. Comparative
      and risk-stratification trials are urgently required and ongoing.

PMID- 27894366
TI  - Evolution of host range in the follicle mite Demodex kutzeri.
AB  - The sequences of four mitochondrial genes were determined for Demodex mites
      isolated from two distantly related species within the family Cervidae, and
      identified morphologically as belonging to the species Demodex kutzeri. The
      sequences were used to test the hypothesis that Demodex are strictly host
      specific, and hence cospeciate with their hosts: (1) The estimated divergence
      time between mites found on elk vs humans agreed closely with a previous estimate
      of the time that these host species last shared a common ancestor, suggesting
      cospeciation of mites and hosts, at least over long evolutionary timescales. (2)
      The extremely low levels of sequence divergence between the mites found on elk vs
      mule deer hosts indicated that these mites belong to the same species, which
      suggests that Demodex are able to move across host species boundaries over
      shorter timescales. Together, the results are consistent with the model that
      Demodex mites are not strict host-specialists, but instead lose the ability to
      move between host lineages gradually.

PMID- 27894365
TI  - Leishmania infantum: illness, transmission profile and risk factors for
      asymptomatic infection in an endemic metropolis in Brazil.
AB  - To evaluate the distribution of asymptomatic infection by Leishmania infantum in
      a metropolis in Brazil with different relative risks (RRs) for disease and risk
      factors associated with the infection, an ecological study was conducted using a
      Bayesian approach to estimate the RR of human visceral leishmaniasis (HVL) based
      on cases between 2008 and 2011. The areas were categorized and selected according
      to disease incidence: low (area-1), medium (area-2) and high (area-3). Cross
      sectional study enrolling 935 children was used to estimate the prevalence of
      infection by L. infantum. Volunteers from these three areas were tested for L.
      infantum infection by ELISA (rK39 and soluble antigens). Infection prevalence
      rates were estimated and compared with the RR of disease. Multilevel logistic
      regression model evaluated the relationship between infection and the analysed
      variables. The RR of HVL was distributed heterogeneously in the municipality. The
      infection prevalence rates were: 34.9% in area-1; 29.3% in area-2; and 33.6% in
      area-3, with no significant differences between these areas. The variables
      'Presence of backyards in the neighbourhood' and 'Younger children' were
      associated with L. infantum infection. We conclude that infection by L. infantum
      affects a significant proportion of the infant population regardless of the RR of
      disease.

PMID- 27894367
TI  - Potential immunological markers for diagnosis of human strongyloidiasis using
      heterologous antigens.
AB  - Strongyloides venezuelensis is a parasitic nematode of rodents that is frequently
      used to obtain heterologous antigens for immunological diagnosis of human
      strongyloidiasis. The aim of this study was to identify antigens from filariform
      larvae of S. venezuelensis for immunodiagnosis of human strongyloidiasis. Soluble
      and membrane fractions from filariform larvae of S. venezuelensis were obtained
      in phosphate saline (SS and SM) and in Tris-HCl buffer (TS and TM), and were
      analysed by Western blotting. Different antigenic components were recognized by
      IgG antibodies from the sera of strongyloidiasis patients. Highest recognition
      was observed for a 30-40 kDa mass range present in all antigenic fractions. The
      band encompassing this mass range was then excised and subjected to mass
      spectrometry for protein identification. Immunoreactive proteins identified in
      the soluble fractions corresponded to metabolic enzymes, whereas cytoskeletal
      proteins and galectins were more abundant in the membrane fractions. These
      results represent the first approach towards identification of S. venezuelensis
      antigens for use in immunodiagnostic assays for human strongyloidiasis.

PMID- 27894369
TI  - Valvar aortico-ventricular tunnel: an insight into the development of the great
      arteries.
AB  - Aorto-left ventricular tunnel is a rare congenital heart lesion, with an
      incidence of <0.1% of all CHD. We present a unique case of a valvar aorto-left
      ventricular tunnel in a neonate, in belief that our findings may shed some light
      on the developmental origins of this lesion.

PMID- 27894370
TI  - 'Aut'-sider: the invisible talent of Simona Concaro?.

PMID- 27894368
TI  - Effects of behavioural activation on the neural basis of other perspective self
      referential processing in subthreshold depression: a functional magnetic
      resonance imaging study.
AB  - BACKGROUND: It has been demonstrated that negatively distorted self-referential
      processing, in which individuals evaluate one's own self, is a pathogenic
      mechanism in subthreshold depression that has a considerable impact on the
      quality of life and carries an elevated risk of developing major depression.
      Behavioural activation (BA) is an effective intervention for depression,
      including subthreshold depression. However, brain mechanisms underlying BA are
      not fully understood. We sought to examine the effect of BA on neural activation
      during other perspective self-referential processing in subthreshold depression.
      METHOD: A total of 56 subjects underwent functional magnetic resonance imaging
      scans during a self-referential task with two viewpoints (self/other) and two
      emotional valences (positive/negative) on two occasions. Between scans, while the
      intervention group (n = 27) received BA therapy, the control group (n = 29) did
      not. RESULTS: The intervention group showed improvement in depressive symptoms,
      increased activation in the dorsal medial prefrontal cortex (dmPFC), and
      increased reaction times during other perspective self-referential processing for
      positive words after the intervention. Also, there was a positive correlation
      between increased activation in the dmPFC and improvement of depressive symptoms.
      Additionally, there was a positive correlation between improvement of depressive
      symptoms and increased reaction times. CONCLUSIONS: BA increased dmPFC activation
      during other perspective self-referential processing with improvement of
      depressive symptoms and increased reaction times which were associated with
      improvement of self-monitoring function. Our results suggest that BA improved
      depressive symptoms and objective monitoring function for subthreshold
      depression.

PMID- 27894371
TI  - Pervasive influence of maternal and paternal criminal offending on early
      childhood development: a population data linkage study.
AB  - BACKGROUND: Parental criminal offending is an established risk factor for
      offending among offspring, but little evidence is available indicating the impact
      of offending on early childhood functioning. We used data from a large Australian
      population cohort to determine associations between exposure to parental
      offending and a range of developmental outcomes at age 5 years. METHOD: Multi
      generation data in 66 477 children and their parents from the New South Wales
      Child Development Study were combined using data linkage. Logistic and
      multinomial regressions tested associations between any and violent offending
      histories of parents (fathers, mothers, or both parents) obtained from official
      records, and multiple measures of early childhood developmental functioning
      (social, emotional-behavioural, cognitive, communication and physical domains)
      obtained from the teacher-reported 2009 Australian Early Development Census.
      RESULTS: Parental offending conferred significantly increased risk of
      vulnerability on all domains, particularly the cognitive domain. Greater risk
      magnitudes were observed for offending by both parents and by mothers than by
      fathers, and for violent than for any offending. For all parental offending
      exposures, vulnerability on multiple domains (where medium to large effects were
      observed) was more likely than on a single domain (small to medium effects).
      Relationships remained significant and of comparable magnitude following
      adjustment for sociodemographic covariates. CONCLUSIONS: The effect of parental
      offending on early childhood developmental outcomes is pervasive, with the
      strongest effects on functioning apparent when both parents engage in violent
      offending. Supporting affected families in early childhood might mitigate both
      early developmental vulnerability and the propensity for later delinquency among
      these offspring.

PMID- 27894373
TI  - Cognitive effects of adjunctive N-acetyl cysteine in psychosis.
AB  - BACKGROUND: Cognitive deficits are predictors of functional outcome in patients
      with psychosis. While conventional antipsychotics are relatively effective on
      positive symptoms, their impact on negative and cognitive symptoms is limited.
      Recent studies have established a link between oxidative stress and
      neurocognitive deficits in psychosis. N-acetylcysteine (NAC), a glutathione
      precursor with glutamatergic properties, has shown efficacy on negative symptoms
      and functioning in patients with schizophrenia and bipolar disorder,
      respectively. However, there are few evidence-based approaches for managing
      cognitive impairment in psychosis. The present study aims to examine the
      cognitive effects of adjunctive NAC treatment in a pooled subgroup of
      participants with psychosis who completed neuropsychological assessment in two
      trials of both schizophrenia and bipolar disorder. METHOD: A sample of 58
      participants were randomized in a double fashion to receive 2 g/day of NAC (n =
      27) or placebo (n = 31) for 24 weeks. Attention, working memory and executive
      function domains were assessed. Differences between cognitive performance at
      baseline and end point were examined using Wilcoxon's test. The Mann-Whitney test
      was used to examine the differences between the NAC and placebo groups at the end
      point. RESULTS: Participants treated with NAC had significantly higher working
      memory performance at week 24 compared with placebo (U = 98.5, p = 0.027).
      CONCLUSIONS: NAC may have an impact on cognitive performance in psychosis, as a
      significant improvement in working memory was observed in the NAC-treated group
      compared with placebo; however, these preliminary data require replication.
      Glutamatergic compounds such as NAC may constitute a step towards the development
      of useful therapies for cognitive impairment in psychosis.

PMID- 27894372
TI  - Affective lability mediates the association between childhood trauma and suicide
      attempts, mixed episodes and co-morbid anxiety disorders in bipolar disorders.
AB  - BACKGROUND: Many studies have shown associations between a history of childhood
      trauma and more severe or complex clinical features of bipolar disorders (BD),
      including suicide attempts and earlier illness onset. However, the
      psychopathological mechanisms underlying these associations are still unknown.
      Here, we investigated whether affective lability mediates the relationship
      between childhood trauma and the severe clinical features of BD. METHOD: A total
      of 342 participants with BD were recruited from France and Norway. Diagnosis and
      clinical characteristics were assessed using the Diagnostic Interview for Genetic
      Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders
      (SCID-I). Affective lability was measured using the short form of the Affective
      Lability Scale (ALS-SF). A history of childhood trauma was assessed using the
      Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the
      SPSS process macro. RESULTS: Using the mediation model and covariation for the
      lifetime number of major mood episodes, affective lability was found to
      statistically mediate the relationship between childhood trauma experiences and
      several clinical variables, including suicide attempts, mixed episodes and
      anxiety disorders. No significant mediation effects were found for rapid cycling
      or age at onset. CONCLUSIONS: Our data suggest that affective lability may
      represent a psychological dimension that mediates the association between
      childhood traumatic experiences and the risk of a more severe or complex clinical
      expression of BD.

PMID- 27894374
TI  - Autologous intratympanic blood patch for presumed perilymphatic fistulas.
AB  - OBJECTIVE: To assess an alternative to bed rest and surgery for suspected
      perilymphatic fistulas using intratympanic blood injections. METHOD: A review was
      conducted of patients' history, physical and audiometric data, before and after
      treatment by intratympanic blood injections performed from 2009 to 2015. RESULTS:
      Twelve ears were identified, with trauma associated with air travel, water sports
      or nose blowing. Ten of these cases had hearing loss, six had vestibular
      symptoms. Four cases had audiological and vestibular symptoms, two had vestibular
      symptoms only, and six had audiological symptoms only. Time-to-treat varied from
      1 day to 30 days. Magnetic resonance imaging scans were obtained for five cases.
      Ten cases received steroids. Six out of seven cases showed improvement of hearing
      loss. Five cases showed positive fistula test results, four with documented
      resolution. Seven cases had full resolution of all symptoms, four had near-full
      resolution and one had no improvement. CONCLUSION: Intratympanic blood injections
      offer an effective alternative to conservative or surgical therapy. Advantages
      include sooner time-to-treat, lower financial costs and decreased psychosocial
      burdens. It allows a more flexible and liberal use of a potential definite
      treatment for perilymphatic fistula.

PMID- 27894375
TI  - Plasmodium knowlesi and human malaria parasites in Khan Phu, Vietnam: Gametocyte
      production in humans and frequent co-infection of mosquitoes.
AB  - Four species of malaria parasite, Plasmodium falciparum, Plasmodium vivax,
      Plasmodium malariae and Plasmodium knowlesi infect humans living in the Khanh Phu
      commune, Khanh Hoa Province, Vietnam. The latter species also infects wild
      macaque monkeys in this region. In order to understand the transmission dynamics
      of the three species, we attempted to detect gametocytes of the three species in
      the blood of infected individuals, and sporozoites in the salivary glands of
      mosquitoes from the same region. For the detection of gametocyte-specific mRNA,
      we targeted region 3 of pfg377, pvs25, pmg and pks25 as indicators of the
      presence of P. falciparum, P. vivax, P. malariae and P. knowlesi gametocytes,
      respectively. Gametocyte-specific mRNA was present in 37, 61, 0 and 47% of people
      infected with P. falciparum (n = 95), P. vivax (n = 69), P. malariae (n = 6) or
      P. knowlesi (n = 32), respectively. We found that 70% of mosquitoes that had P.
      knowlesi in their salivary glands also carried human malaria parasites,
      suggesting that mosquitoes are infected with P. knowlesi from human infections.

PMID- 27894376
TI  - Brain substrates underlying auditory speech priming in healthy listeners and
      listeners with schizophrenia.
AB  - BACKGROUND: Under 'cocktail party' listening conditions, healthy listeners and
      listeners with schizophrenia can use temporally pre-presented auditory speech
      priming (ASP) stimuli to improve target-speech recognition, even though listeners
      with schizophrenia are more vulnerable to informational speech masking. METHOD:
      Using functional magnetic resonance imaging, this study searched for both brain
      substrates underlying the unmasking effect of ASP in 16 healthy controls and 22
      patients with schizophrenia, and brain substrates underlying schizophrenia
      related speech-recognition deficits under speech-masking conditions. RESULTS: In
      both controls and patients, introducing the ASP condition (against the auditory
      non-speech-priming condition) not only activated the left superior temporal gyrus
      (STG) and left posterior middle temporal gyrus (pMTG), but also enhanced
      functional connectivity of the left STG/pMTG with the left caudate. It also
      enhanced functional connectivity of the left STG/pMTG with the left pars
      triangularis of the inferior frontal gyrus (TriIFG) in controls and that with the
      left Rolandic operculum in patients. The strength of functional connectivity
      between the left STG and left TriIFG was correlated with target-speech
      recognition under the speech-masking condition in both controls and patients, but
      reduced in patients. CONCLUSIONS: The left STG/pMTG and their ASP-related
      functional connectivity with both the left caudate and some frontal regions (the
      left TriIFG in healthy listeners and the left Rolandic operculum in listeners
      with schizophrenia) are involved in the unmasking effect of ASP, possibly through
      facilitating the following processes: masker-signal inhibition, target-speech
      encoding, and speech production. The schizophrenia-related reduction of
      functional connectivity between the left STG and left TriIFG augments the
      vulnerability of speech recognition to speech masking.

PMID- 27894377
TI  - Effect of a spiritual care training program for staff on patient outcomes.
AB  - OBJECTIVE: Physicians and nurses do not assess spirituality routinely, even
      though spiritual care is a vital part of palliative care for patients with an
      advanced serious illness. The aim of our study was to determine whether a
      training program for healthcare professionals on spirituality and the taking of a
      spiritual history would result in improved patient quality of life (QoL) and
      spiritual well-being. METHOD: This was a cluster-controlled trial of a spiritual
      care training program for palliative care doctors and nurses. Three of seven
      clinical teams (clusters) received the intervention, while the other four served
      as controls. Included patients were newly referred to the palliative care
      service, had an estimated survival of more than one month, and were aware of
      their diagnosis and prognosis. The primary outcome measure was the Functional
      Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) patient
      reported questionnaire, which patients completed at two timepoints. Total FACIT
      Sp score includes the Functional Assessment of Cancer Therapy-General (FACT-G)
      questionnaire, which measures overall quality of life, as well as a spiritual
      well-being score. RESULTS: Some 144 patients completed the FACIT-Sp at both
      timepoints-74 in the control group and 70 in the intervention group. The change
      in overall quality of life, measured by change in FACT-G scores, was 3.89 points
      (95% confidence interval [CI 95%] = -0.42 to 8.19, p = 0.076) higher in the
      intervention group than in the control group. The difference between the
      intervention and control groups in terms of change in spiritual well-being was
      0.32 (CI 95% = -2.23 to 2.88, p = 0.804). SIGNIFICANCE OF RESULTS: A brief
      spiritual care training program can possibly help bring about enhanced
      improvement of global patient QoL, but the effect on patients' spiritual well
      being was not as evident in our participants. Further study with larger sample
      sizes is needed to allow for more definite conclusions to be drawn.

PMID- 27894378
TI  - An experimental approach to linguistic representation.
AB  - Within the cognitive sciences, most researchers assume that it is the job of
      linguists to investigate how language is represented, and that they do so largely
      by building theories based on explicit judgments about patterns of acceptability 
      whereas it is the task of psychologists to determine how language is processed,
      and that in doing so, they do not typically question the linguists'
      representational assumptions. We challenge this division of labor by arguing that
      structural priming provides an implicit method of investigating linguistic
      representations that should end the current reliance on acceptability judgments.
      Moreover, structural priming has now reached sufficient methodological maturity
      to provide substantial evidence about such representations. We argue that
      evidence from speakers' tendency to repeat their own and others' structural
      choices supports a linguistic architecture involving a single shallow level of
      syntax connected to a semantic level containing information about quantification,
      thematic relations, and information structure, as well as to a phonological
      level. Many of the linguistic distinctions often used to support complex (or
      multilevel) syntactic structure are instead captured by semantics; however, the
      syntactic level includes some specification of "missing" elements that are not
      realized at the phonological level. We also show that structural priming provides
      evidence about the consistency of representations across languages and about
      language development. In sum, we propose that structural priming provides a new
      basis for understanding the nature of language.

PMID- 27894379
TI  - Precis of Talking to Our Selves: Reflection, Ignorance, and Agency.
AB  - Does it make sense for people to hold one another responsible for what they do,
      as happens in countless social interactions every day? One of the most unsettling
      lessons from recent psychological research is that people are routinely mistaken
      about the origins of their behavior. Yet philosophical orthodoxy holds that the
      exercise of morally responsible agency typically requires accurate self
      awareness. If the orthodoxy is right, and the psychology is to be believed,
      people characteristically fail to meet the standards of morally responsible
      agency, and we are faced with the possibility of skepticism about agency. Unlike
      many philosophers, I accept the unsettling lesson from psychology. I insist,
      however, that we are not driven to skepticism. Instead, we should reject the
      requirement of accurate self-awareness for morally responsible agency. In Talking
      to Our Selves I develop a dialogic theory, where the exercise of morally
      responsible agency emerges through a collaborative conversational process by
      which human beings, although afflicted with a remarkable degree of self
      ignorance, are able to realize their values in their lives.

PMID- 27894380
TI  - An attention and interpretation bias for illness-specific information in chronic
      fatigue syndrome.
AB  - BACKGROUND: Studies have shown that specific cognitions and behaviours play a
      role in maintaining chronic fatigue syndrome (CFS). However, little research has
      investigated illness-specific cognitive processing in CFS. This study
      investigated whether CFS participants had an attentional bias for CFS-related
      stimuli and a tendency to interpret ambiguous information in a somatic way. It
      also determined whether cognitive processing biases were associated with co
      morbidity, attentional control or self-reported unhelpful cognitions and
      behaviours. METHOD: A total of 52 CFS and 51 healthy participants completed self
      report measures of symptoms, disability, mood, cognitions and behaviours.
      Participants also completed three experimental tasks, two designed specifically
      to tap into CFS salient cognitions: (i) visual-probe task measuring attentional
      bias to illness (somatic symptoms and disability) v. neutral words; (ii)
      interpretive bias task measuring positive v. somatic interpretations of ambiguous
      information; and (iii) the Attention Network Test measuring general attentional
      control. RESULTS: Compared with controls, CFS participants showed a significant
      attentional bias for fatigue-related words and were significantly more likely to
      interpret ambiguous information in a somatic way, controlling for depression and
      anxiety. CFS participants had significantly poorer attentional control than
      healthy individuals. Attention and interpretation biases were associated with
      fear/avoidance beliefs. Somatic interpretations were also associated with all-or
      nothing behaviour and catastrophizing. CONCLUSIONS: People with CFS have illness
      specific biases which may play a part in maintaining symptoms by reinforcing
      unhelpful illness beliefs and behaviours. Enhancing adaptive processing, such as
      positive interpretation biases and more flexible attention allocation, may
      provide beneficial intervention targets.

PMID- 27894382
TI  - [Study of tumor necrosis factor-alpha induced protein 8 like-2 expression in
      peripheral blood mononuclear cells of patients with acute respiratory distress
      syndrome correlate with disease severity].
AB  - OBJECTIVE: To demonstrate the effect of tumor necrosis factor-alpha induced
      protein 8 like-2 (TIPE2) expression in patients with acute respiratory distress
      syndrome (ARDS) and its mechanism. METHODS: A prospective observation was
      conducted. Thirty-nine patients with ARDS admitted to department of emergency of
      PLA General Hospital from July 2013 to July 2015 were enrolled, and 35 healthy
      persons served as control group. The acute physiology and chronic health
      evaluation II (APACHE II) score within 24 hours after admission, blood gas
      analysis, procalcitonin (PCT), and C-reactive protein (CRP) were recorded. The
      mRNA expressions of TIPE2 in peripheral blood mononuclear cell (PBMC) and myxoma
      resistance protein 1 (MX1) in plasma were determined by real-time quantitative
      reverse transcription-polymerase chain reaction (RT-PCR). The correlations were
      analyzed by Spearman rank correlation analysis. RESULTS: The mean of APACHE II
      score in 39 patients with ARDS was 25+/-3, the mean of PCT was (1.85+/-0.41)
      MUg/L, and the mean of CRP was (18.0+/-3.0) mg/L. The TIPE2 mRNA expression in
      PBMC of ARDS patients was significantly down-regulated as compared with that of
      healthy control group (2-Kappa KappaCt: 3.28+/-0.15 vs. 8.87+/-0.20, P < 0.001),
      and the MX-1 mRNA expression in plasma was significantly higher than that of
      healthy control group (2-Kappa KappaCt: 39.44+/-0.46 vs. 20.10+/-0.32, P <
      0.001). It was shown by correlation analysis results that the TIPE2 mRNA
      expression was negatively correlated with MX1 mRNA expression (r = -0.630, P <
      0.001), so as APACHE II score (r = -0.781, P < 0.001), but no correlation was
      found between TIPE2 mRNA and PCT as well as CRP (r value was 0.143 and 0.330,
      respectively, both P > 0.05). The MX1 mRNA expression was positively correlated
      with APACHE II score (r = 0.893, P < 0.001), but no correlation was found between
      MX1 mRNA and PCT as well as CRP (r value was 0.230 and 0.210, respectively, both
      P > 0.05). CONCLUSIONS: TIPE2 expression was decreased in ARDS patients, which
      negatively correlate with disease severity, and indicate TIPE2 might be involved
      in the pathogenic process of ARDS.

PMID- 27894381
TI  - Understanding barriers to fruit and vegetable intake in the Australian
      Longitudinal Study of Indigenous Children: a mixed-methods approach.
AB  - OBJECTIVE: To identify barriers to fruit and vegetable intake for Indigenous
      Australian children and quantify factors related to these barriers, to help
      understand why children do not meet recommendations for fruit and vegetable
      intake. DESIGN: We examined factors related to carer-reported barriers using
      multilevel Poisson models (robust variance); a key informant focus group guided
      our interpretation of findings. SETTING: Eleven diverse sites across Australia.
      SUBJECTS: Australian Indigenous children and their carers (N 1230) participating
      in the Longitudinal Study of Indigenous Children. RESULTS: Almost half (45 %; n
      555/1230) of carers reported barriers to their children's fruit and vegetable
      intake. Dislike of fruit and vegetables was the most common barrier, reported by
      32.9 % of carers; however, we identified few factors associated with dislike.
      Carers were more than ten times less likely to report barriers to accessing fruit
      and vegetables if they lived large cities v. very remote areas. Within urban and
      inner regional areas, child and carer well-being, financial security, suitable
      housing and community cohesion promoted access to fruit and vegetables.
      CONCLUSIONS: In this national Indigenous Australian sample, almost half of carers
      faced barriers to providing their children with a healthy diet. Both remote/outer
      regional carers and disadvantaged urban/inner regional carers faced problems
      accessing fruit and vegetables for their children. Where vegetables were
      accessible, children's dislike was a substantial barrier. Nutrition promotion
      must address the broader family, community, environmental and cultural contexts
      that impact nutrition, and should draw on the strengths of Indigenous families
      and communities.

PMID- 27894383
TI  - [Integrated diagnosis and treatment of scar].
AB  - Scar is the common disease in the field of burn and plastic surgery, and its
      diagnosis and treatment should be involved in overwhelming majority hospitals.
      There are many substandard methods and medical hidden dangers in diagnosis and
      treatment of scar, due to the unevenness of doctors' clinical experience.
      According to the classification of integral scar and diabrotic scar, the problems
      related to diagnosis and treatment of scar are systemically summarized and
      normalized in this article for decrease in the incidence of adverse events and
      medical hidden dangers.

PMID- 27894384
TI  - [Reconstruction of anal stenosis induced by scar contracture after repair of
      defect in perineal region with paraumbilical flap using random pattern flap].
AB  - Objective: To investigate the method and timing of reconstruction of anal
      stenosis induced by scar contracture after repair of defect in perineal region
      with paraumbilical flap using random pattern flap. Methods: Ten patients who
      suffered anal stenosis induced by scar contracture after the first phase repair
      of defect of perineal region with paraumbilical flap were hospitalized from July
      2009 to September 2015. Eight patients were with central type scar contracture of
      perineal region after healing of burn wound, and two patients were with lesion of
      perineal region which had been excised. In 6 to 8 weeks after the first phase
      surgery, two or three random pattern flaps were designed around the narrow anus
      in the survived paraumbilical flap. After thorough release of the narrow anus,
      the random pattern flaps were transferred to enlarge the anus. The tip of the
      lifted triangular flap was transferred to insert into the anal canal. The skin of
      anal canal or rectal mucosa was pulled out to be crossly-stitched with the flap.
      Results: All the patients' narrow anuses were released and enlarged with one
      operation, and the diameters of the narrow anuses were enlarged to 2.0 to 3.0 cm.
      During follow-up of 6 to 36 months, the anal stenosis was totally released, and
      the symptom of difficult defecation was significantly improved; 7 patients were
      excellent and 3 patients were good with evaluation of clinical criteria of anus
      function; no symptom of anal stenosis or rectal mucosal prolapse was observed any
      more. Conclusions: In 6 to 8 weeks post repair of defect in perineal region with
      paraumbilical flap, designing of random pattern flap in the survived
      paraumbilical flap to enlarge and reconstruct the narrow anus has good
      therapeutic effects on anatomical narrow and difficult defecation.

PMID- 27894385
TI  - [Effect of expanded lateral thoracic abdominal flap transferred with pedicle on
      repairing large area of hypertrophic scar after burn of the upper extremity].
AB  - Objective: To observe the effect of expanded lateral thoracic abdominal flap
      transferred with pedicle on repairing large area of hypertrophic scar after burn
      of the upper extremity. Methods: Twelve patients with large area of secondary
      hypertrophic scar 8 month to 3 years after healing of burn wound on the upper
      extremity were hospitalized in Zhengzhou First People's Hospital from October
      2008 to October 2015, with scar area ranging from 11 cm*7 cm to 20 cm*10 cm. Five
      patients were with limited straightening and bending of elbow. The scars were
      reconstructed with ipsilateral expanded lateral thoracic abdominal flap or that
      combined with expanded upper extremity flap according to the area of scar.
      Lateral thoracic abdominal incision was located near the anterior axillary line,
      and upper extremity incision was located near scar edge. A capsule cavity was
      formed by blunt dissection in the superficial fascia layer. Expander with
      suitable capacity was implanted with the injection pot being built-in. Volume of
      water reaching 1 time to 3 times of the capacity of expander was injected for
      excessive expanding. The expanded lateral thoracic abdominal flap supplied by
      lateral thoracic cutaneous artery and expanded upper extremity flap were
      dissected after the completion of expanding. The expanded upper extremity flap
      was advanced locally to cover the surrounding secondary wound after resection of
      hypertrophic scar. The expanded lateral thoracic abdominal flap was transferred
      with pedicle to reconstruct scar, with pedicle being sutured in skin tube-like
      shape, and the flap donor site was sutured directly. Flap pedicle separation was
      carried out 3 weeks after surgery. Anti-scar treatment was carried out after
      healing of sutured area. Results: Totally 18 expanders were implanted, without
      complications such as infection, exposure of expander, and so on. The areas of
      expanded lateral thoracic abdominal flaps were from 11 cm*7 cm to 16 cm*11 cm.
      The combined application of expanded upper extremity flaps with area ranging from
      8 cm*4 cm to 9 cm*6 cm was used in 6 patients. All the flaps survived with
      incision healed. The color, texture, and thickness of skin area repaired by flap
      were close to those of the normal skin of upper extremity after 6 months to 2
      years' follow-up afer discharge. The limited straightening and bending of elbow
      in 5 patients were rectified. Obvious linear scar was observed in the sutured
      area of surgery in 3 patients, while light linear scar was observed in the
      sutured area of surgery in 9 patients. Conclusions: Expanded lateral thoracic
      abdominal flap has constant blood vessel and is easy to be dissected. It can
      achieve well reconstruction of appearance and function in repairing large area of
      hypertrophic scar after burn of the upper extremity.

PMID- 27894386
TI  - [Study of the correlation between the expression of angiotensin II and its
      receptors and collagen deposition in human keloid].
AB  - Objective: To study the correlation between the expression of angiotensin II,
      angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R) and
      collagen deposition in human keloid. Methods: The keloid from 19 keloid patients
      and normal skin from 13 patients performed with free skin transplantation
      hospitalized in our unit from May 2014 to January 2015 were obtained. The
      expressions of angiotensin II, AT1R, and AT2R were detected by
      immunohistochemical staining, and the results were semi-quantitatively analyzed
      by immunohistochemical scoring. The expression of collagen in keloid was detected
      by picrosirius-red staining, and the percentage of total collagen was calculated.
      Data were processed with t test. The expressions of angiotensin II, AT1R, AT2R
      and the total content of collagen of 13 keloid patients were analyzed by Pearson
      correlation analysis. Results: (1) There was negative or probably positive
      expression of angiotensin II in normal skin tissue, mainly distributed in the
      epidermal basal layer. The expression of angiotensin II was strong in keloid,
      most distributed in spinous layer and basal layer of epidermis and most region of
      dermis, and was strongly positive in most cells, and most cells were fibroblasts.
      The expressions of AT1R and AT2R were similar to angiotensin II in two types of
      tissue. The expressions of angiotensin II, AT1R, and AT2R in keloid scored (305+/
      34), (281+/-32), and (285+/-25) points, respectively, which were significantly
      higher than those in normal tissue [respectively (54+/-17), (89+/-47), and (97+/
      32) points, with t values from 12.03 to 23.21, P values below 0.01]. (2) The
      total content of collagen in keloid was (88+/-4)%. There was a lot of thick and
      dense type Icollagen in keloid, with massive structure and distributed like
      bamboo segment and arranged in disorder. The expression of type III collagen was
      increased, which was distributed scatteredly around type Icollagen. (3) There
      were positive correlations between the expressions of angiotensin II, AT1R, AT2R
      and the total content of collagen in keloid (with r values from 0.452 to 0.720, P
      values below 0.05). Conclusions: The expressions of angiotensin II, AT1R, and
      AT2R were abnormally increased in human keloid, which may play an important role
      in the collagen deposition of keloid.

PMID- 27894388
TI  - [Analysis of distribution and drug resistance of pathogens isolated from 541
      hospitalized children with burn infection].
AB  - Objective: To investigate the distribution and drug resistance of pathogens
      isolated from hospitalized children with burn infection. Methods: Totally 541
      patients were hospitalized in Fujian Medical University Union Hospital, the 180th
      Hospital of Chinese People's Liberation Army(PLA), the 92th Hospital of PLA, and
      Longyan First Hospital from January 2013 to December 2015. Totally 848 clinical
      specimens (blood, catheter tip attachments, wound exudate, etc.) were collected
      for pathogen detection. After being identified by an automatic microbiological
      identification system, drug resistance of pathogens to 41 commonly-used
      antibiotics in clinic including gentamicin, aztreonam, erythromycin, clindamycin,
      etc. was tested by K-B paper disk diffusion method or minimal inhibitory
      concentration detection method. The SPSS 20.0 statistical software was used to
      analyze the following subjects: the detection rates of pathogens in different
      years, from different hospitals, and with different sources, the distribution of
      gram-negative bacteria, gram-positive bacteria, and fungi, the distribution of
      major pathogens, the detection rate of methicillin-resistant Staphylococcus, the
      resistant rates of common gram-positive bacteria and gram-negative bacteria to
      antibiotics. Results: The total detection rate of pathogens was 35.14% (298/848).
      The detection rates of pathogens were 52.29% (114/218), 33.20% (83/250), and
      26.58% (101/380) in 2013, 2014, and 2015 respectively, 38.45% (198/515), 51.43%
      (18/35), 71.70% (38/53), and 17.96% (44/245) from Fujian Medical University Union
      Hospital, the 180th Hospital of PLA, the 92th Hospital of PLA, and Longyan First
      Hospital respectively, and 136/261, 8/137, 3/4, and 7/48 from wound exudate,
      blood, drainage fluid or tissue fluid, and the other specimens (including
      catheter tip attachments, sputum, feces) respectively. Among the 298 pathogens,
      159 (53.36%) strains were gram-positive bacteria, 129 (43.29%) strains were gram
      negative bacteria, and 10 (3.36%) strains were fungi. The detection rate of
      Staphylococcus aureus was the highest, totally 68 strains, accounting for 22.82%,
      followed by Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus
      epidermidis, with 37, 31, and 22 strains, accounting for 12.42%, 10.40%, and
      7.38% respectively. Among Staphylococcus aureus, methicillin-resistant
      Staphylococcus aureus (MRSA) accounted for 70.59% (48/68). Among Staphylococcus
      epidermidis, methicillin-resistant Staphylococcus epidermidis (MRSE) accounted
      for 68.18% (15/22). The resistant rates of MRSA and MRSE to penicillin and
      ampicillin were all 100.0%, and the resistant rates of MRSA to erythromycin,
      tetracycline, clindamycin and those of MRSE to erythromycin, cotrimoxazole were
      high. The high resistant rate of Pseudomonas aeruginosa towards antibiotics was
      detected with cotrimoxazole (83.3%) only. The resistant rates of Acinetobacter
      baumannii towards piperacillin, ceftazidime, and cotrimoxazole were high (from
      58.8% to 71.4%). Conclusions: During the three years, there is large difference
      in the detection rate of pathogens from these four hospitals in Fujian province.
      The majority of pathogens were Gram-positive bacteria. The four dominant
      pathogens were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter
      baumannii, and Staphylococcus epidermidis. Most of the pathogens were resistant
      to antibiotics commonly used in clinic in different degree, especially MRSA, MRSE
      and Acinetobacter baumannii, which showed high resistance towards antibiotics.

PMID- 27894389
TI  - [Qualitative study on the current status of hospitalized burn children's quality
      of life].
AB  - Objective: To explore the current status of hospitalized burn children's quality
      of life, so as to lay foundation for carrying out the related intervention in
      future. Methods: Using qualitative research method, semi-structured interviews
      were conducted on 11 parents of burn children hospitalized in Department of Burns
      of Fujian Medical University Union Hospital from March to May 2016. Then the data
      were analyzed and concluded with phenomenological analysis method to refine the
      themes. Results: Parents' description about the current status of hospitalized
      burn children's quality of life could be summed up into four areas: physiology,
      psychology, social development, and family; and in six themes: obvious itching
      symptom, limited movement development, night terror and constant cry because of
      fear, reduced social game, negative attachment type, and parents under multiple
      pressures. Conclusions: Burn brings serious harm to children's physical and
      mental development, as well as negative effects on the parents, thus lowering the
      children's quality of life. Medical workers should increase knowledge and
      attention of it, and carry out targeted health management project.

PMID- 27894387
TI  - [Effect of hydrocinnamoyl-L-valyl pyrrolidine on healing quality of deep partial
      thickness scald wound in mice].
AB  - Objective: To observe the effect of Toll interleukin-1 recptor homology/BB-loop
      mimetic hydrocinnamoyl-L-valyl pyrrolidine (AS-1) on the healing quality of deep
      partial-thickness scald wound in mice. Methods: Forty-two adult C57BL/6 mice were
      divided into sham injury group (SI), scald group (S), early AS-1 treatment group
      (EAT), early dimethyl sulfoxide (DMSO) control group (EDC), late AS-1 treatment
      group (LAT), late DMSO control group (LDC) according to the random number table,
      with 7 mice in each group. Mice in group SI were sham injured without other
      treatment. Deep partial-thickness scald model with 10% total body surface area
      was reproduced on the back of the other mice, and the wound was treated by daily
      wound cleaning with saline and dressing changing with vaseline gauze after
      injury. Mice in group EAT and those in group LAT were intraperitoneally injected
      with 20 mg/mL AS-1 50 mg/kg each day respectively from post scald hour (PSH) 8
      and post scald day (PSD) 15 on. Mice in group EDC and those in group LDC were
      intraperitoneally injected with 20 mg/mL DMSO 50 mg/kg each day respectively from
      PSH 8 and PSD 15 on. On PSD 21, the gross condition of wound healing of mice with
      scald was observed, and the wound healing rate was calculated. Tissue samples of
      healed wound were collected and stained with HE and Masson respectively to
      observe the histomorphological change and fibrosis of collagen, and the
      percentage of fibrosis of collagen was calculated. The mRNA expressions of
      interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha),
      transforming growth factor beta1 (TGF-beta1), matrix metalloproteinase-1 (MMP-1),
      tissue inhibitors of metalloproteinase 1 (TIMP-1), connective tissue growth
      factor (CTGF), type I collagen and type III collagen in healed wound tissue were
      detected by real time fluorescent quantitive reverse transcription polymerase
      chain reaction. The protein expressions of type I collagen and type III collagen
      in healed wound tissue were detected by Western blotting. Skin tissue of mice in
      group SI at the same area as that observed and collected in mice with scald was
      performed with the same observation and detection as mentioned above at the same
      time. Data were processed with one-way analysis of variance and Tukey test.
      Results: On PSD 21, no abnormal appearance was found in skin tissue of mice in
      group SI. Wounds of mice in group EAT were healed completely without scar
      formation, while those in the other four groups were not completely healed with
      scars formed in different degree. The wound healing rate of mice in group EAT was
      (97+/-4)%, close to that of group SI (100%, q=1.753, P>0.05), and both of them
      were obviously higher than those of groups S, EDC, LAT, and LDC [respectively
      (83+/-8)%, (87+/-6)%, (85+/-9)%, and (85+/-7)%, with q values from 4.819 to
      6.803, P<0.05 or P<0.01]. On PSD 21, no abnormal appearance was found in
      morphology of skin tissue of mice in group SI. The morphology of healed wound
      tissue of mice in group EAT was close to that in group SI, with little epidermis
      hyalinosis and few newly formed collagen fibers arranged orderly. Epidermis
      hyalinosis in band- or flake-shape and obvious proliferation of collagen fibers
      arranged disorderly were observed in healed wound tissue of mice in the other
      four groups. Much infiltration of inflammatory cells was found in group S. The
      percentage of fibrosis of collagen in healed wound tissue of mice in group EAT
      was (30+/-3)%, close to that of group SI [(30+/-4)%, q=0.159, P>0.05], and both
      of them were obviously lower than those of groups S, EDC, LAT, and LDC
      [respectively (86+/-9)%, (74+/-5)%, (82+/-4)%, and (82+/-7)%, with q values from
      12.080 to 15.530, P values below 0.01]. On PSD 21, compared with those of group
      SI, the mRNA expressions of IL-1beta, TNF-alpha, TGF-beta1, MMP-1, and CTGF in
      healed wound tissue of mice in group S, the mRNA expressions of TGF-beta1 in
      healed wound tissue of mice in groups EDC and LDC, and the mRNA expression of MMP
      1 in healed wound tissue of mice in group LAT were significantly increased (with
      q values from 4.039 to 5.232, P values below 0.05), while the mRNA expression of
      TIMP-1 in healed wound tissue of mice in group S was significantly decreased
      (q=4.921, P<0.05). Compared with those of group S, the mRNA expressions of IL
      1beta, TNF-alpha, TGF-beta1, MMP-1, and CTGF in healed wound tissue of mice in
      group EAT and the mRNA expressions of IL-1beta and CTGF in healed wound tissue of
      mice in group LAT were significantly decreased (with q values from 4.418 to
      6.402, P<0.05 or P<0.01), while the mRNA expressions of TIMP-1 in healed wound
      tissue of mice in groups EAT and LAT were significantly increased (with q values
      respectively 3.929 and 8.299, P<0.05 or P<0.01). Compared with those of group SI,
      the mRNA and protein expressions of type III collagen in healed wound tissue of
      mice in the other groups and the mRNA and protein expressions of type I collagen
      in healed wound tissue of mice in groups S, EDC, LAT, and LDC were significantly
      increased (with q values from 7.054 to 11.650, P values below 0.01). Compared
      with those of group EAT, the mRNA and protein expressions of type I collagen in
      healed wound tissue of mice in groups S, EDC, LAT, and LDC were significantly
      increased (with q values from 5.156 to 7.451, P<0.05 or P<0.01). Conclusions: AS
      1 can effectively promote wound healing and reduce fibrosis degree in the early
      stage of inflammation response after deep partial-thickness scald in mice, which
      may be related to its effect in decreasing the expression of inflammation related
      factors IL-1beta and TNF-alpha and fibrosis related factors TGF-beta1, MMP-1,
      CTGF, and type I collagen.

PMID- 27894390
TI  - [Effects of different fluid resuscitation program on renal function in swine
      during shock stage of severe burn].
AB  - Objective: To explore the effects of different fluid resuscitation program on
      renal function in swine during shock stage of severe burn. Methods: Twenty-four
      Guangxi Bama miniature swine were inflicted with 40% total body surface area on
      the back, and then they were divided into four groups according to the random
      number table, with 6 swine in each group. At post injury hour (PIH) 2, swine in
      succinylated gelatin group (S), hydroxyethyl starch group (H), and allogeneic
      plasma group (A) were respectively resuscitated with succinylated gelatin,
      hydroxyethyl starch 130/0.4, and plasma according to burn shock " domestic
      general" resuscitation formula, and swine in Parkland group (P) were resuscitated
      with lactated Ringer's solution according to Parkland formula. Hemodynamic
      indexes including heart rate, blood pressure, urine volume, pulmonary capillary
      wedge pressure, and central venous pressure before injury, at the first and
      second PIH 24 were recorded. The volume of resuscitation fluid was calculated at
      the first and second PIH 24. Blood and urine samples were collected before injury
      and at PIH 4, 8, 24, and 48, and then serum creatinine and urea nitrogen were
      detected by automatic biochemical analyzer, urine microalbumin and urine
      creatinine were detected by automated urine analyzer and the ratio of which was
      calculated. The renal tissue of swine in each group was obtained at PIH 48, and
      the pathologic changes were observed by optical microscopy and electron
      microscope. Data were processed with analysis of variance of repeated
      measurement, one-way analysis of variance, and LSD test. Results: (1) The
      hemodynamic indexes of swine in each group were similar before injury and at the
      first and second PIH 24 (with P values above 0.05). Compared with those before
      injury, except that the heart rate of swine in group A had no significant change
      at the first PIH 24 (P>0.05), the heart rate of swine in each group was
      significantly increased at the first and second PIH 24 (with P values below
      0.01); except that the systolic blood pressure of swine in group P was
      significantly increased at the first and second PIH 24 (P<0.05 or P<0.01), there
      were no significant changes of systolic blood pressure and diastolic blood
      pressure of swine in each group at the first and second PIH 24 (with P values
      above 0.05); except that urine volume of swine in groups S and A was
      significantly decreased at the first PIH 24 (P<0.05 or P<0.01), there were no
      significant change of urine volume of swine in each group at the first and second
      PIH 24 (with P values above 0.05); pulmonary capillary wedge pressure and central
      venous pressure of swine in each group were significantly increased at the first
      and second PIH 24 (P<0.05 or P<0.01). (2) Compared with that in group A, the
      volume of resuscitation fluid of swine in groups S and H had no significant
      change in the first and second PIH 24 (with P values above 0.05), while it was
      significantly increased in group P in the first PIH 24 and significantly
      decreased in the second PIH 24 (with P values below 0.05). (3) Compared with
      those in group A, except that serum creatinine of swine in group H was
      significantly increased at PIH 24 and significantly increased in group P at PIH
      4, 8, 24, and 48, urea nitrogen of swine in group P was significantly decreased
      at PIH 4 and 8 and significantly increased at PIH 48, the ratio of urine
      microalbumin to urine creatinine of swine in group P was significantly increased
      at PIH 8, 24, and 48 (P<0.05 or P<0.01), serum creatinine, urea nitrogen, and the
      ratio of urine microalbumin to urine creatinine of swine in each group had no
      significant change at each time point (with P values above 0.05). Serum
      creatinine of swine in group P was (125+/-16) MUmol/L at PIH 24, which was
      significantly higher than that before injury [(75+/-13) MUmol/L, P<0.05]. Urea
      nitrogen of swine in group S was (2.90+/-1.17) MUmol/L at PIH 48, which was
      significantly lower than that before injury [(4.60+/-0.47) MUmol/L, P<0.05]; urea
      nitrogen of swine in group H was (4.82+/-0.82) MUmol/L at PIH 4, which was
      significantly higher than that before injury [(3.80+/-0.73) MUmol/L, P<0.05];
      urea nitrogen values of swine in group A were respectively (4.80+/-0.33), (4.92+/
      0.35), and (2.60+/-0.27) MUmol/L at PIH 4, 8, and 48, while those at PIH 4, 8
      were significantly higher and at PIH 48 was significantly lower than the value
      before injury [(3.93+/-0.32) MUmol/L, with P values below 0.01]. The ratios of
      urine microalbumin to urine creatinine of swine in group P were respectively
      (106.7+/-16.4) and (171.6+/-36.9) mg/mmol at PIH 24 and 48, which were
      significantly higher than the ratio before injury [(59.0+/-3.0) mg/mmol, with P
      values below 0.01]. The serum creatinine, urea nitrogen, and the ratio of urine
      microalbumin to urine creatinine of swine in each group at the other time points
      were similar to those before injury (with P values above 0.05). (4) The renal
      tissue of swine in the four groups had no obvious pathological change.
      Conclusions: According to the renal function results, fluid resuscitation with
      electrolyte and colloids are better than with lactated Ringer's solution in swine
      during shock stage of burn injury, while natural colloids and succinylated
      gelatin have similar effects, and both are superior to hydroxyethyl starch
      130/0.4.

PMID- 27894391
TI  - [Advances in the research of diagnosis techniques of burn depth].
AB  - The accurate diagnosis of burn depth is one of the important problems in the
      field of burn surgery. The diagnosis accuracy rate is directly related to the
      treatment plan and effect. The existed clinical diagnosis methods mainly depend
      on the experience of burn surgeon, making the accuracy rate from 50% to 65%. In
      order to improve the accuracy rate of clinical burn depth diagnosis, a large
      number of diagnosis methods based on imaging are proposed, however, all of the
      methods are still in the stage of experimental research. In this paper, the
      research advances on the diagnosis techniques of burn depth are summarized, both
      the advantages and the shortcomings are pointed, and the development trend of
      diagnosis techniques of burn depth is expected.

PMID- 27894392
TI  - [Advances in the research on effect of detecting skin perfusion pressure in
      clinic].
AB  - Skin perfusion pressure (SPP) is the perfusion pressure at the skin level, and it
      can serve as an index of microcirculation in skin and subcutaneous tissue. SPP
      can be measured simply, with less injury and high reproducibility in a short
      time, without interfering vascular calcification. It has been widely used in
      various fields, including evaluation of critical limb ischaemia and effect of
      vascular surgery, selection of proper level of amputation, and prediction of
      wound healing. So far, there is no relevant reports about the application of SPP
      in China. This article reviews the clinical application of SPP abroad.

PMID- 27894393
TI  - The effect of the ginger on the apoptosis of hippochampal cells according to the
      expression of BAX and Cyclin D1 genes and histological characteristics of brain
      in streptozotocin male diabetic rats.
AB  - Diabetes is the most common endocrine disorder in humans with multiple
      complications including nervous system damages. The aim of the present study was
      to determine the effect of ginger extract on apoptosis of the neurons of
      hippocampus, via evaluation of BAX and Cyclin D1 and also histological analysis,
      in male diabetic rats. In this experimental study, 60 Wistar rats (220 +/- 30gr)
      were conducted in 5 groups as follow: diabetic group treated with saline (group
      1), normal group treated with saline (group 2), diabetic group treated with
      ginger (group 3), diabetic group treated with ginger-insulin (group 4), diabetic
      group treated with insulin (group 5). STZ (60 mg/kg) was intraperitoneally used
      to induce the diabetes. Expression levels of BAX and Cyclin D1 were examined
      using Real-Time PCR technique and the normality of neurons was evaluated using
      H&E staining method. The results showed that blood glucose level significantly
      decreased in group 4 when compared to group 1. In molecular analysis, there was
      no significant difference between groups regarding the expression of BAX gens,
      while, the expression of Cyclin D1 were significantly decreased in group 4
      compared with group 1. Histological analysis revealed that pathological symptoms
      were lower in group 4 than the other diabetic groups. The results of present
      study showed that the ginger in addition to lowering blood sugar level, changes
      the expression of Cyclin D1 gene and histological characteristics in a positive
      manner. This means that the ginger may protects neurons of the hippocampus from
      apoptosis in diabetic patients.

PMID- 27894394
TI  - Differences of cell surface marker expression between bone marrow- and kidney
      derived murine mesenchymal stromal cells and fibroblasts.
AB  - Mesenchymal stromal cells (MSC) are undifferentiated, multipotent adult cells
      with regenerative properties. They are particularly relevant for therapeutic
      approaches due to the simplicity of their isolation and cultivation. Since MSC
      show an expression pattern of cell surface marker, which is almost identical to
      fibroblasts, many attempts have been made to address the similarities and
      differences between MSC and fibroblasts. In this study we aimed to isolate murine
      MSC from bone marrow (BM) and kidney to characterize them in comparison to
      fibroblasts. Cells were isolated from murine kidney, BM and abdominal skin by
      plastic adherence and subsequently characterized by analysing their capability to
      build colony-forming unit-fibroblasts (CFU-F), their morphology, their
      proliferation, expression of telomerase activity and cell surface antigens as
      well as their differentiation capacity. Plastic adherent cells from the 3 mouse
      tissues showed similar morphology, proliferation profiles and CFU-F building
      capacities. However, while MSC from BM and kidney differentiated into the
      adipogenic, chondrogenic and osteogenic direction, fibroblasts were not able to
      do so efficiently. In addition, a tendency for lower expression of telomerase was
      found in the fibroblast population. Proliferating cells from kidney and BM
      expressed the MSC-specific cell surface markers CD105 and Sca-1 on a
      significantly higher and CD117 on a significantly lower level compared to
      fibroblasts and were thereby distinguishable from fibroblasts. Furthermore, we
      found that certain CD markers were specifically expressed on a higher level,
      either in BM-derived cells or fibroblasts. This study demonstrates that murine
      MSC isolated from different organs express certain specific markers, which enable
      their discrimination.

PMID- 27894395
TI  - Relationship between hepatitis B virus reverse transcriptase 181 mutation and S
      gene mutation in hepatitis B virus chronically infected patients.
AB  - This study aims to explore clinical significance of HBV rt181 mutation. Serum
      samples were collected from 226 CHB patients with no anti-viral treatment, and 72
      patients with adefovir dipivoxil treatment over 1 year. HBV genes of reverse
      transcriptase regions were amplified by nested PCR. HBV DNA in pre-S/S regions
      sequences were determined by sequencing. Mutations in HBV were characterized by
      mutational analysis. Results indicated that resistant mutation was found in 16
      samples (7.08%) with no anti-viral treatment. It showed higher prevalence in
      patients with adefovir dipivoxil treated samples 30/72(41.67%). Mutation sites of
      pre-existing and adefovir dipivoxil induced resistance were different (adefovir
      dipivoxil induced resistance mode is rtA181T/V, and pre-existing mode is the
      other). Resistance mutation was found just in genotype C patients. Among 25
      containing rtA181T/V mutation patients, 7 rtA181T mutation cases with sW172L, 6
      rtA181T mutation cases with sW172*, 12 rtA181Vmutation cases with sL173F. In
      conclusion, mutation sites of pre-existing and adefovir dipivoxil induced
      resistance were different. HBV genotype C is prone to occur resistance mutation
      than genotype B. rtA181T mutation was accompanied with not only sW172 * mutation,
      but also sW172L mutation, rtA181V mutation was accompanied with sL173F mutation
      or Pre-S2 initiation codon to termination mutation.

PMID- 27894396
TI  - Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction
      of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines.
AB  - Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic
      activities. However, the efficacy of EA has not been examined in neuro
      inflammatory conditions. Microglia making the innate immune system of the central
      nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory
      processes. In this study, neuro-protective effects of EA on cuprizone (Cup)
      induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow
      containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly
      in the corpus callosum (CC). EA was administered at different doses (40 or 80
      mg/kg body weight/day/i.p) from the first day of the Cup diet. Microglia
      activation (microgliosis) and expression of microglia related chemokines during
      Cup challenge were examined. Results shows that EA significantly decreased the
      number of activated microglia cells (Iba-1+ cells) and also restricted
      proliferation of these cell population (Iba-1+/Ki67+ cells) in dose dependent
      manner. Consequently, concentration of microglial pro-inflammatory chemokines
      including monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP
      1/CCL2), and macrophage inflammatory protein 1-alpha/Chemokine (C-C motif) ligand
      3 (MIP-1-alpha/CCL3) dramatically reduced in CC after EA treatment. According to
      this results, we conclude that EA is a suitable therapeutic agent for moderation
      brain damages in neuro-inflammatory diseases.

PMID- 27894397
TI  - Isolation and identification of culturable halophilic bacteria with producing
      hydrolytic enzyme from Incheh Broun hypersaline wetland in Iran.
AB  - Incheh Broun hypersaline wetland is located near the border of Turkmenistan in
      thenorth of Iran. This wetland is notable because of salinity (280g/l) and
      alteration in pH range (2.8 to 6.8). Eastern part of wetland is affected by
      wastewater of iodine extraction factory.  Samples were taken from soil, water and
      salt. Totally, 400 bacterial strains were isolated of which 194 strains were Gram
      positive bacilli, 184 strains were Gram-negative rod and 22 strains were Gram
      positive cocci. According to phylogenetic analysis of 16S rRNA, selected strains
      were placed in three taxonomic phyla including Firmicutes, Actinobacteria and
      Gammaproteobacteria. Optimum growth was evaluated for salt and 22 strains were
      found to be moderate halophile and 33 strains were halotolerant. Production of
      lipase, amylase, gelatinase and protease was examined. Gram-positive bacilli were
      the main producers of hydrolytic enzymes. Gelatinase and protease were the most
      frequent enzymes. Gram-positive cocci were the main producers of lipase but they
      didn't produce amylase.

PMID- 27894398
TI  - miR-488 determines coat pigmentation by down-regulating the pigment-producing
      gene pro-opiomelanocortin.
AB  - Coat color is a key economic trait in wool- and fur-producing animals. Coat color
      is controlled by complex mechanisms. Pro-opiomelanocortin (POMC) is a gene
      involved in pigment formation. Previous studies suggested that miR-488 might
      target the POMC mRNA. This study aimed to determine whether miR-488 could affect
      coat color by regulating POMC and to explore the regulatory roles of miR-488 on
      coat color in mammals. A dual fluorescence report vector containing the 3'-UTR of
      POMC was built to determine whether miR-488 could post-transcriptionally regulate
      POMC expression. Then, a eukaryotic vector expressing miR-488 was built and
      transfected into mouse keratinocytes to confirm the regulatory mechanism in
      vitro. Compared with gray mice, the expression of POMC mRNA was 3.36-fold higher
      in black mice and 1.29-fold higher in brown mice. The results showed that miR-488
      could control mice coat color by combining with the 3'-UTR seed sequence of POMC
      mRNA to achieve the degradation of POMC mRNA, therefore playing a role in POMC
      expression. This study revealed the roles of miR-488 in animal coat color and
      enriches our knowledge about the determination of coat color in mammals.

PMID- 27894399
TI  - Effect of iguratimod and methotrexate on RANKL and OPG expression in serum and IL
      1beta-induced fibroblast-like synoviocytes from patients with rheumatoid
      arthritis.
AB  - The receptor activator of nuclear factor kappaB ligand (RANKL)/receptor activator
      of nuclear factor kappaB (RANK)/osteoprotegerin (OPG) system plays a key role in
      rheumatoid arthritis (RA)-associated bone erosion. The upregulation of the
      RANKL/OPG ratio promotes bone erosion. The objective of this study is to explore
      the effects of iguratimod, a small-molecule disease-modifying antirheumatic drug
      (DMARD), alone or in combination with methotrexate (MTX), on RANKL and OPG
      expression in RA. We performed an enzyme-linked immunosorbent assay (ELISA) to
      investigate the modulatory effects of iguratimod, MTX, or their combination on
      serum RANKL and OPG levels of patients with RA before and after treatment for 12
      and 24 weeks. Furthermore, fibroblast-like synoviocytes (FLS) from patients with
      RA were interleukin (IL)-1beta-stimulated and then treated with different
      concentrations of iguratimod, MTX, or both, and RANKL and OPG expressions were
      investigated by using ELISA, quantitative real-time polymerase chain reaction
      (qPCR) and western blot analysis. We found that RANKL levels and the RANKL/OPG
      ratio significantly decreased in both serum and IL-1beta-induced RA FLS after
      treatment. Moreover, combination therapy with iguratimod and MTX showed an even
      stronger inhibition than each drug alone did. Our results suggest that iguratimod
      and MTX, especially in combination, efficaciously protected against bone erosion
      by suppressing the production of RANKL.

PMID- 27894400
TI  - Genetic diversity of the Dwarf honeybee (Apis florea Fabricius, 1787) populations
      based on microsatellite markers.
AB  - Apis florea is one of two species of small, wild honeybee. The present study was
      conducted to evaluate the genetic diversity of Apis florea honeybee from 48 nests
      (colonies) using microsatellite markers in the South of Iran. All honeybee
      samples were analyzed for six microsatellite loci (A88, A107, A7, B124, A113 and
      A35). The six loci had different numbers of alleles in the sampled colonies
      ranging from 7 (loci A107) to 3 (loci A7, A35). Gene diversity in Apis florea
      ranged from 0.491 to 0.595. This range probably reflects the spreading of nests
      in a large region with a varied climate. Phylogenetic tree showed two distinct
      clusters including a) Minab region samples and b) Bandar Abbas, Bandar Khamir and
      Qeshm Island regions. All of these regions are geographically rich, having varied
      vegetation and climate conditions. Our findings are an important contribution to
      the methods of studying distribution and conservation of Apis florea.

PMID- 27894401
TI  - Association between the cytotoxic T-lymphocyte antigen-4 mutations and the
      susceptibility to systemic lupus erythematosus; Contribution markers of
      inflammation and oxidative stress.
AB  - : The cytotoxic T lymphocyte antigen-4 (CTLA-4) also known as CD152 (cluster of
      differentiation 152) is a crucial negative regulator of the immune system. This
      protein receptor provides negative signals in order to suppress T-cell activation
      and immune attack against self-antigens, although its role is unclear.  The
      ability of CTLA-4 to limit T cell-mediated immune response has made it a major
      target in treatment of tumors and autoimmune diseases such as systemic lupus
      erythematosus (SLE). In this study, we investigated whether CTLA-4 G-1661A and
      CTLA-4 T-1722C mutations are associated with SLE. So one hundred nine SLE
      patients and 101 gender and age-matched unrelated healthy controls were recruited
      for this case-control study. The promoter mutations were detected by PCR-RFLP,
      neopterin, malondialdehyde (MDA) and serum lipid concentration were determined by
      HPLC and enzyme assay, respectively. RESULT: We found that both codominant (AA
      vs. GG) and recessive (AA vs. GA+GG) CTLA-4 G-1661A mutation significantly
      decreased the risk of SLE by 1.7 and 3.7 times, respectively.  Interestingly, SLE
      patients with AA genotypes of CTLA-4 G-1661A have lower neopterin and MDA
      concentration compared with GA+GG genotypes. The overall distribution of CTLA-4 T
      1722C genotypes and alleles in SLE patients were similar to those in control
      group. In conclusion, our findings showed, that there is an association between
      systemic inflammatory markers, oxidative stress and the CTLA-4 G-1661A GG+AG
      genotypes, MDA and neopterin which are the most conventional risk factors for
      coronary heart disease, therefore these mutations may be consider as a risk
      factor for susceptibility to heart disease in SLE patients.

PMID- 27894402
TI  - HSP90 inhibitor enhances anti-proliferative and apoptotic effects of celecoxib on
      HT-29 colorectal cancer cells via increasing BAX/BCL-2 ratio.
AB  - Due to the high prevalence and mortality rate of colorectal cancer (CRC), new
      treatment approaches like combination therapy seem to be necessary. The
      relationship between chronic inflammation and colorectal cancer development and
      progression has been shown to be important. Celecoxib, a selective COX-2
      inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been
      approved for cancer therapy and prevention. Because of cardiovascular side
      effects of COX-2 inhibitors, combination therapy may improve the therapeutic
      profile. 17-Demethoxy-17-allylamino geldanamycin (17-AAG), a heat shock protein
      90 (HSP90) inhibitor, shows anti-inflammatory effects via down-regulation of the
      key mediators of inflammation such as Nuclear Factor kappaB (NF-kB), JAK/Signal
      Transducer and Activator of Transcription (JAK/STAT). Thus, we studied the
      effect(s) of combination of 17-AAG and celecoxib on HT-29 cells viability and
      apoptosis induction. Based on MTT results, we showed an increase in the
      inhibitory effect of celecoxib when combined with 17-AAG, especially at low a
      concentration of celecoxib.  Flow cytometry analysis demonstrated that apoptosis
      induction is probably the mechanism of additive inhibitory effects of 17-AAG and
      celecoxib combination. To explore the possible mechanism of apoptosis induction
      by 17-AAG and celecoxib combination, levels of BAX and BCL-2 proteins were
      determined by western blotting. The BAX/BCL-2 ratio in the combination group was
      increased compared to 17-AAG or celecoxib alone, mainly via decreasing BCL-2
      levels. In conclusion, 17-AAG, increased inhibitory effects of celecoxib on HT-29
      cells, probably by induction of apoptosis.

PMID- 27894403
TI  - Conditioned medium from neural stem cells inhibits glioma cell growth.
AB  - Malignant glioma is one of the most common brain tumors in the central nervous
      system. Although the significant progress has been made in recent years, the
      mortality is still high and 5-year survival rate is still very low. One of the
      leading causes to the high mortality for glioma patients is metastasis and
      invasion. An efficient method to control the tumor metastasis is a promising way
      to treat the glioma. Previous reports indicated that neural stem cells (NSCs)
      were served as a delivery vector to the anti-glioma therapy. Here, we used the
      conditioned medium from rat NSCs (NSC-CM) to culture the human glioblastoma cell
      lines. We found that NSC-CM could inhibit the glioma cell growth, invasion and
      migration in vitro and attenuate the tumor growth in vivo. Furthermore, this anti
      glioma effect was mediated by the inactivation of mitogen activated protein
      kinase (MAPK) pathway. Above all, this study provided the direct evidence to put
      forward a simple and efficient method in the inhibition of glioma cells/tumor
      growth, potentially advancing the anti-glioma therapy.

PMID- 27894404
TI  - Streptozotocin induces neurite outgrowth via PI3K-Akt and glycogen synthase
      kinase 3beta in Neuro2a cells.
AB  - Streptozotocin (STZ), a naturally occurring chemical, is toxic to the various
      kinds of cells such as insulin-producing beta cells. However, the beneficial
      effect of STZ on neuronal cells such as neurite outgrowth-inducing activity has
      been unknown. In this study, we examined the effect of STZ on neurite outgrowth
      in mouse neuronal Neuro2a cells. STZ (0.01 mM~5 mM) exerted remarkable neurite
      outgrowth-inducing activity in Neuro2a cells in a concentration dependent manner.
      STZ also had the same neurite outgrowth-inducing activity as that of retinoic
      acid (RA), which is well known neurite outgrowth inducer. As with the result of
      RA treatment, STZ administration increased MAP2-positive cells. The MAP2-positive
      cells reflect neurite outgrowth-induced cells. STZ (0.01 mM~5 mM) did not induce
      cell death, but significantly decreased cell proliferation. The serine/threonine
      kinase Akt, a downstream target of phosphatidylinositol-3 kinase (PI3K), was
      transiently phosphorylated at Ser473 and at Thr303 by STZ (5 mM) administration.
      Glycogen synthase kinase 3beta (GSK3beta), which has been reported to be
      inactivated by Akt, was also transiently phosphorylated at Ser9 by STZ (5 mM)
      administration. In addition, a blocker of PI3K, LY294002 (10 MUM), significantly
      attenuated STZ-induced neurite outgrowth. These results suggest that STZ induces
      neurite outgrowth via activation of PI3K-Akt signaling pathway and GSK3beta
      inhibition.

PMID- 27894406
TI  - Vincristine promotes migration and invasion of colorectal cancer HCT116 cells
      through RhoA/ROCK/ Myosin light chain pathway.
AB  - Vincristine is an antitumor vinca alkaloid isolated from vinca rosea, and is a
      medication used to treat a number of types of cancer. In this study, we
      investigated the impact of vincristine on oncogenic phenotypes of human
      colorectal cancer HCT116 cells. MTT assay demonstrated that vincristine showed a
      obviously inhibitory effect on cell growth compared to non-treated cells.
      However, Transwell assay showed that vincristine promoted migration and invasion
      of HCT116 cells in vitro in a concentration-dependent manner between 0.5 and 15
      MUM vincristine treatment, whereas cell growth showed no remarkable difference
      within the same concentration range. Additionally, Western blot analysis showed
      that vincristine significantly elevated RhoA activity and Myosin light chain
      (MLC) phosphorylation, suggesting the involvement of RhoA/ROCK pathway in the
      vincristine-induced enhancement of cellular motility. Furthermore, we found that
      both the siRNA for RhoA and ROCK inhibitor Y27632 attenuated the phosphorylation
      of MLC, as well as vincristine-induced migration and invasion. These data
      indicate that vincristine enhanced migration and invasion of HCT116 cells
      possibly through stimulating RhoA/ROCK/MLC signaling pathway.

PMID- 27894405
TI  - Inhibition of matrix metalloproteins 9 attenuated Candida albicans induced
      inflammation in mouse cornea.
AB  - Since the severe corneal ulceration of mouse cornea is known to occur with
      inflammation. As one of imperative matrix metalloproteinase, the potential roles
      of matrix metalloproteins 9 (MMP9) in corneal ulceration and keratitis are still
      unveiled caused by fungal invasion. In this study, Candida albicans (CA)
      inoculated wild-type KM mice cornea was used as a model pathogen in corneal
      inflammation.  CA invasion significantly stimulated the expression of collagen IV
      and MMP9 detected by RT-PCR, Real-time PCR and Immunofluorescent staining in
      mouse cornea as soon as 6 hours post infection, and relatively decreased at 1 day
      post infection. For examining the role of MMP9 in fungal keratitis, the mice
      corneas were subconjunctivally injected MMP9 antibody or recombinant MMP9 protein
      6 hours prior to CA inoculation, using rabbit IgG as control. Subconjunctival
      injection of recombinant MMP9 protein prior to CA inoculation enhanced, whereas
      MMP9 antibody attenuated corneal ulceration and inflammation, examining basement
      membrane, fungal load, myeloperoxidase (MPO) and proinflammatory cytokines
      including Macrophage inflammatory protein 2 (MIP2), Interleukin-1beta (IL-1beta)
      and Tumor necrosis factor-alpha (TNF-alpha). Inhibition of MMP9 could potentially
      attenuate Candida albicans induced inflammation in mouse cornea.

PMID- 27894407
TI  - MiRNA-378 controls cell proliferation in rabbit umbilical cord mesenymal stem
      cells.
AB  - Mesenchymal stem cells (MSC) are known to have the ability to differentiate into
      various lineages of mesenchymal tissue. They are widely distributed in a variety
      of tissues in the body and are also present in the foetal environment. MicroRNAs
      (miRNAs) are a fundamental class of biological molecules that play a crucial role
      in development. In this study, microRNA-378 and its predicted target (Sufu,
      suppressor of fused homolog) were used to study proliferation of rabbit umbilical
      cord mesenymal stem cells, luciferase reporter assay was used to assess and
      confirm the binding sequence of 3'untranslated region between microRNA-378 and
      Sufu. The results showed that miRNA-378 overexpression reduced Sufu gene, and
      promoted cell proliferation of rabbit umbilical cord mesenymal stem cells via
      cell viability and BrdU testing, which molecular mechanisms were down-regulation
      of apoptosis genes after miRNA-378 overexpression. In conclusion, our research
      shows that the microRNA-378 promoted the cell proliferation of rabbit umbilical
      cord mesenymal stem cells, and this mechanism was miRNA-378 reduced the
      expression of Sufu, increased cell proliferation.

PMID- 27894408
TI  - Body girdle reduced fat deposition and altered other body parameters in rats.
AB  - Many women favor in wearing foundation garments to shape their body and show
      satisfactory figures. However, few investigations have been conducted on the
      physiological impact of wearing tight garments on the body. In this study, we
      used girdled rats that were fed with a high fat diet to investigate their
      physiological condition including alterations in food intake, body weight, fat
      deposition, and hormone concentrations. Over the experiment period, girdled rats
      maintained normal plasma and liver cholesterol and triglyceride. Leptin level in
      girdled rats was significantly lower than that in normal control. The fat tissue
      of girdled rats was more active in secretion of leptin, which might be mediated
      by mTOR signaling. Girdled rats showed no difference in hematology analysis
      during the experiment period. This study showed that a body girdle can
      significantly reduce fat deposition and alter other body parameters in rats.

PMID- 27894409
TI  - The effects of mitochondrial DNA deletion and copy number variations on different
      exercise intensities in highly trained swimmers.
AB  - It has been suggested that heavy exercise might increase oxidative stress,
      causing mitochondrial DNA (mtDNA) mutations as well as DNA mutations and changes
      in the mtDNA copy number in cells. mtDNA4977 deletion is one of the most common
      deletions seen on mitochondria. We hypothesize association between exercise
      induced oxidative stress and mtDNA damage in peripheral blood lymphocytes (PBLs)
      of highly trained swimmers. Therefore we studied the mtDNA4977 deletion level,
      mtDNA copy number and their relationship with cellular ATP and oxidative stress
      status in PBLs of swimmers. 8 highly trained and 8 normal trained swimmers and 8
      non-athlete subjects were included in the study. The mtDNA4977 deletion and
      amount of mtDNA were measured using RT-PCR method whereas
      dichlorohydrofluoroscein (DCF) assay method was used to assess cellular oxidative
      stress and ATP levels were measured using bioluminescence method. Even though an
      increase in mtDNA4977 deletion was found in all study groups, the difference was
      not statistically significant (p=0.98). The mtDNA copy numbers were found to be
      surprisingly high in highly trained swimmers compared to normal trained swimmers
      and non-athlete subjects by 4.03 fold (p= 0.0002) and 5.58 fold (p=0.0003),
      respectively. No significant differences were found between groups by means of
      intracellular ATP levels (p=0.406) and oxidative stress (p=0.430).  No
      correlation was found between mtDNA copy number and intracellular ATP content of
      the PBLs (p=0.703). Our results suggest that heavy training does not have a
      specific effect on mtDNA4977 deletion but it may be affecting mitochondrial copy
      numbers which may act as a compensatory mechanism related to ATP levels in blood.

PMID- 27894410
TI  - Association of HFE gene mutations with nonalcoholic fatty liver disease in the
      Iranian population.
AB  - To determine whether the HFE gene variants H63D and C282Y are associated with
      NAFLD in persons with type 2 diabetes, we conducted a case-control study
      including 145 case of NAFLD patients with a history of type 2 diabetes and 145
      matching control. The genomic DNA was extracted from the peripheral venous blood
      and the genotyping of HFE gene mutations was analyzed using the PCR-RFLP
      technique. Statistical analysis was performed using SPSS 12.0 software by chi2
      test, t test and ANOVA (P<0.05). Data showed no increased frequency of HFE
      mutations in persons with type 2 diabetes and no association between H63D
      mutation and NAFLD in the study population. Also, we analyzed index of
      physiological variables including FBS, lipid profile (TC, TG, LDL-C, and HDL-C),
      BMI, HbA1c, and micro albuminuria and Cr levels). Data showed there are no
      relationship between these indexes and HFE gene mutations and either NAFLD as a
      complication of diabetes. But our results showed a relationship between C282Y
      mutation and NAFLD in persons with type 2 diabetes. C282Y mutation might be a
      genetic marker of NAFLD in Iranian population.

PMID- 27894411
TI  - Allele specific-PCR and melting curve analysis showed relatively high frequency
      of beta-casein gene A1 allele in Iranian Holstein, Simmental and native cows.
AB  - There are two allelic forms of A1 and A2 of beta-casein gene in dairy cattle.
      Proteolytic digestion of bovine beta-casein A1 type produces bioactive peptide of
      beta-casomorphin-7 known as milk devil. beta-casomorphin-7 causes many diseases,
      including type 1 diabetes, cardiovascular disease syndrome, sudden death and
      madness. The aim of the present study was to determine the different allelic
      forms of beta-casein gene in Iranian Holstein, Simmental and native cattle in
      order to identify A1 and A2 variants. The blood samples were collected randomly
      and DNA was extracted using modified salting out method. An 854 bp fragment
      including part of exon 7 and part of intron 6 of beta-casein gene was amplified
      by allele specific polymerase chain reaction (AS-PCR). Also, the accuracy of AS
      PCR genotyping has been confirmed by melting temperature curve analysis using
      Real-time PCR machinery. The comparison of observed allele and genotype frequency
      among the studied breeds was performed using the Fisher exact and Chi-squared
      test, respectively by SAS program. Obtained results showed the A1 allele
      frequencies of 50, 51.57, 54.5, 49.4 and 46.6% in Holstein, Simmental, Sistani,
      Taleshi and Mazandarani cattle populations, respectively. The chi-square test was
      shown that no any populations were in Hardy-Weinberg equilibrium for studied
      marker locus. Comparison and analysis of the test results for allelic frequency
      showed no any significant differences between breeds (P>0.05). The frequency of
      observed genotypes only differs significantly between Holstein and Taleshi breeds
      but no any statistically significant differences were found for other breeds
      (P>0.05). A relatively high frequency of beta-casein A1 allele was observed in
      Iranian native cattle. Therefore, determine the genotypes and preference alleles
      A2 in these native and commercial cattle is recommended.

PMID- 27894412
TI  - The most common genes involved in epigenetics modifications among Iranian
      patients with breast cancer: A systematic review.
AB  - Breast cancer, with a lifelong risk of one in nine, is the most common cancer
      among women. In Iran, breast cancer is one of the growing and important women's
      health problems. Several environmental, genetic and epigenetics factors have been
      suggested to have a role in breast cancer development. Epigenetics alterations
      are heritable changes in gene expression that occur without causing any change in
      DNA sequence. DNA methylation as a main epigenetics modification in human cancer
      is found as a promising biomarker in early detection of breast cancer.
      Association between epigenetics changes of many gene promoters with the risk of
      breast cancer has been investigated worldwide. This aberrant methylation may be
      occur in specific genes related to cell cycle, cell adhesion, apoptosis and DNA
      repairing mechanisms and results in silencing of these important genes. In this
      review study, we have gathered all the data until December 2015 about epigenetics
      modifications among Iranian population with breast cancer.  We searched
      international web databases such as: PubMed, Scopus, and Persian web databases;
      IranMedex and Magiran to investigate the association of epigenetics change and
      incidence of breast cancer among Iranian population. Using "methylation" or
      "epigenetics" key words and "Iran" as affiliation, all the published data were
      31. After arbitrary limitation in search keywords the result have been 20
      articles.  Data analysis show that "ER-alpha" and "E-Cadherin" are most common
      studied genes in epigenetics modifications. Also, maximum studies were done in
      Tehran and Tabriz. We thought that more studies will be helpful to reveal the
      relation of methylation status in candidate genes with the breast cancer risk in
      Iranian populations.

PMID- 27894413
TI  - Targeting of BCR-ABL: Lessons learned from BCR-ABL inhibition.
AB  - In 1960 researchers reported that balanced translocation between chromosomes 22
      and 9 resulted in the generation of Philadelphia chromosome. This breakthrough
      revolutionized our knowledge related to leukemia biology and contemporary studies
      revealed that chromosomal translocation resulted in the fusion between the 5'
      segment of BCR gene and 3' segment of the ABL gene to form BCR/ABL fusion gene.
      Research over the years has progressively and systematically improved our
      understanding of the genetic and proteomic basis of Leukemia. Genome-wide
      profiling studies, including genome sequencing and microarray analysis, have
      helped us in identification of different intracellular signaling cascades that
      are frequently mutated in Leukemia.  We partition this multi-component review
      into different sections related to biochemical characteristics of BCR-ABL+ cells,
      underlying mechanism of generation of mutations and crosstalk of BCR-ABL with
      various intracellular signaling cascades. We also summarize how BCR-ABL encoding
      mRNA is negatively regulated by different miRNAs and the strategies which are
      currently being used to effectively target BCR-ABL protein. We also provide an
      overview of the natural products which have been used for targeting of BCR-ABL
      protein. Better understanding of the protein network of Philadelphia positive
      leukemic cells will prove to be helpful in getting a step closer to personalized
      medicine.

PMID- 27894414
TI  - ANRIL rs2383207 polymorphism and coronary artery disease (CAD) risk: a meta
      analysis with observational studies.
AB  - Some studies investigated the association of antisense non-coding RNA in the INK4
      locus (ANRIL) rs2383207 polymorphism with coronary artery disease (CAD) risk.
      However, the result was still inconsistent. The aim of this study was to
      investigate whether there is an association between the ANRIL rs2383207
      polymorphism and CAD risk. We carried out a PubMed (Medline), EMBASE database
      search covering all published articles. The strength of association between ANRIL
      rs2383207 polymorphism and CAD risk was assessed by calculating OR with 95% CI. A
      total of 13 case-control studies involving 6796 cases and 9956 controls were
      included in this meta-analysis. ANRIL rs2383207polymorphism was associated with a
      significantly an increased risk of CAD (OR=1.47; 95%CI, 1.33-1.62). We also found
      that this polymorphism increased CAD risk in Caucasians (OR=1.51; 95%CI, 1.28
      1.77) and Asians (OR=1.42; 95%CI, 1.26-1.61). In the subgroup analysis according
      to gender, both women and men were significantly associated with the increased
      risk of CAD (OR=1.36; 95%CI, 1.03-1.79 and OR=1.58; 95%CI, 1.20-2.09). In the
      subgroup analysis by age, ANRIL rs2383207 polymorphism showed significant results
      in old CAD patients and young CAD patients (OR=1.32; 95%CI, 1.20-1.44 and
      OR=1.53; 95%CI, 1.32-1.77). Furthermore, this polymorphism also influenced
      myocardial infarction risk (OR=1.75; 95%CI, 1.24-2.47). Even the studies with
      adjustment for age, gender, smoking were included, the significant association
      was also observed (OR=1.43; 95%CI, 1.26-1.62). In conclusion, this meta-analysis
      suggested that ANRIL rs2383207 polymorphism is associated with CAD risk.

PMID- 27894415
TI  - Intercellular adhesion molecule-1 polymorphisms, K469E and G261R and
      susceptibility to vasculitis and rheumatoid arthritis: a meta-analysis.
AB  - The aim of this study was to determine whether intercellular adhesion molecule-1
      (ICAM-1) polymorphisms are associated with susceptibility to vasculitis or
      rheumatoid arthritis (RA). Meta-analyses were performed to assess the
      associations between K469E and G241R polymorphisms of ICAM-1 and vasculitis or
      RA. A total of 12 studies on 1,368 patients and 1,922 controls, which comprised 8
      vasculitis studies and 4 RA studies, were included in the meta-analysis. We found
      no significant association between vasculitis and K469E E allele among the
      various subjects (OR = 1.238, 95% CI = 0.9781-1.566, p = 0.076). However, an
      association between vasculitis and K469E polymorphism was observed under
      homozygote contrast (OR = 1.443, 95% CI = 1.084-1.920, p = 0.012). Stratification
      by ethnicity and vasculitis type showed no association between vasculitis and 1
      K469E polymorphism under heterozygote contrast. In addition, the meta-analysis
      revealed a significant association between the ICAM-1 G241R R allele and Behcet's
      disease (BD) (OR = 3.261, 95% CI = 1.653-6.434, p = 0.001), but not giant cell
      arteritis. Moreover, the meta-analysis indicated an association between RA and
      the R allele and RR+ RG genotype of the ICAM-1 G241R polymorphism (OR = 2.014,
      95% CI = 1.215-3.339, p = 0.007; OR = 2.394, 95% CI = 1.354-4.235, p = 0.003).
      This meta-analysis suggests that the K469E polymorphism is associated with
      susceptibility to vasculitis, and that the G241R polymorphism is associated with
      susceptibility to BD and RA.

PMID- 27894416
TI  - Australian university smoke-free policy implementation: a staff and student
      survey.
AB  - Issue addressed Universities represent important settings for the implementation
      of public health initiatives such as smoke-free policies. The study aimed to
      assess staff and student attitudes towards policy enforcement and compliance as
      well as the acceptability of the provision of cessation support in this setting.
      Methods A cross-sectional study was conducted following the introduction of a
      designated-areas partial smoke-free policy at two campuses of one Australian
      university in 2014. Staff (n=533) and students (n=3060) completed separate online
      surveys assessing attitudes towards smoke-free policy enforcement and compliance,
      and acceptability of university-provided cessation support. Results Students held
      significantly stronger beliefs than staff that the smoke-free policy required
      staff enforcement (69% vs 60%) and violation penalties (67% vs 60%; both P's
      <0.01); however, most staff (66%) did not believe enforcement was part of their
      role. Only 55% of student smokers were aware that the university provided any
      cessation support. 'Free or cheap nicotine replacement therapy' (65%) and 'free
      stop smoking counselling service' (60%) were the most popular strategies student
      smokers thought the university should provide. Conclusions University staff and
      students hold conflicting views over the need for policy enforcement and who is
      responsible for enforcement roles. Students view the university as an acceptable
      setting for the provision of smoking cessation support. So what? Where staff are
      expected to enforce smoke-free policies, specific education and training should
      be provided. Ongoing monitoring of compliance and enforcement behaviour appears
      necessary to avoid the pervasive kind of non-compliance to smoke-free policies
      that have been seen in other settings.

PMID- 27894418
TI  - Discovery of methylfarnesoate as the annelid brain hormone reveals an ancient
      role of sesquiterpenoids in reproduction.
AB  - Animals require molecular signals to determine when to divert resources from
      somatic functions to reproduction. This decision is vital in animals that
      reproduce in an all-or-nothing mode, such as bristle worms: females committed to
      reproduction spend roughly half their body mass for yolk and egg production;
      following mass spawning, the parents die. An enigmatic brain hormone activity
      suppresses reproduction. We now identify this hormone as the sesquiterpenoid
      methylfarnesoate. Methylfarnesoate suppresses transcript levels of the yolk
      precursor Vitellogenin both in cell culture and in vivo, directly inhibiting a
      central energy-costly step of reproductive maturation. We reveal that contrary to
      common assumptions, sesquiterpenoids are ancient animal hormones present in
      marine and terrestrial lophotrochozoans. In turn, insecticides targeting this
      pathway suppress vitellogenesis in cultured worm cells. These findings challenge
      current views of animal hormone evolution, and indicate that non-target species
      and marine ecosystems are susceptible to commonly used insect larvicides.

PMID- 27894419
TI  - Epidermal cell turnover across tight junctions based on Kelvin's
      tetrakaidecahedron cell shape.
AB  - In multicellular organisms, cells adopt various shapes, from flattened sheets of
      endothelium to dendritic neurons, that allow the cells to function effectively.
      Here, we elucidated the unique shape of cells in the cornified stratified
      epithelia of the mammalian epidermis that allows them to achieve homeostasis of
      the tight junction (TJ) barrier. Using intimate in vivo 3D imaging, we found that
      the basic shape of TJ-bearing cells is a flattened Kelvin's tetrakaidecahedron (f
      TKD), an optimal shape for filling space. In vivo live imaging further elucidated
      the dynamic replacement of TJs on the edges of f-TKD cells that enables the TJ
      bearing cells to translocate across the TJ barrier. We propose a spatiotemporal
      orchestration model of f-TKD cell turnover, where in the classic context of 'form
      follows function', cell shape provides a fundamental basis for the barrier
      homeostasis and physical strength of cornified stratified epithelia.

PMID- 27894417
TI  - Oral transfer of chemical cues, growth proteins and hormones in social insects.
AB  - Social insects frequently engage in oral fluid exchange - trophallaxis - between
      adults, and between adults and larvae. Although trophallaxis is widely considered
      a food-sharing mechanism, we hypothesized that endogenous components of this
      fluid might underlie a novel means of chemical communication between colony
      members. Through protein and small-molecule mass spectrometry and RNA sequencing,
      we found that trophallactic fluid in the ant Camponotus floridanus contains a set
      of specific digestion- and non-digestion related proteins, as well as
      hydrocarbons, microRNAs, and a key developmental regulator, juvenile hormone.
      When C. floridanus workers' food was supplemented with this hormone, the larvae
      they reared via trophallaxis were twice as likely to complete metamorphosis and
      became larger workers. Comparison of trophallactic fluid proteins across social
      insect species revealed that many are regulators of growth, development and
      behavioral maturation. These results suggest that trophallaxis plays previously
      unsuspected roles in communication and enables communal control of colony
      phenotypes.

PMID- 27894421
TI  - Nonoperative Management of Blunt Solid Organ Injury in Pediatric Surgery.
AB  - In the last decade, higher rates of nonoperative management of liver, spleen, and
      kidney injuries have been achieved. An algorithmic approach may improve success
      on a national level. Factors for success include management strategy based on
      physiologic status of the child, early attempt at resuscitation using blood
      products, and appropriate use of adjuncts. Shorter hospitalizations are
      appropriate for children who have not bled significantly, and discharge
      instructions facilitate the safety of early discharge. Although routine imaging
      is not required for liver or spleen injury, symptoms should prompt reevaluation.
      Reimaging of renal injuries remains in common use.

PMID- 27894422
TI  - Vascular Access in the Pediatric Population.
AB  - Vascular access procedures are an important and frequent component of the day-to
      day practice of the pediatric surgeon. Most access procedures can be performed
      percutaneously via Seldinger or modified Seldinger technique and are aided by
      technology, such as ultrasound and fluoroscopy. Complications, such as infection,
      do occur, and the pediatric surgeon should be able to diagnose and treat these
      when they arise. The indications, techniques, and complications of vascular
      access are covered in this article.

PMID- 27894423
TI  - Incarcerated Pediatric Hernias.
AB  - Indirect inguinal hernias are the most commonly incarcerated hernias in children,
      with a higher incidence in low birth weight and premature infants. Contralateral
      groin exploration to evaluate for a patent processus vaginalis or subclinical
      hernia is controversial, given that most never progress to clinical hernias. Most
      indirect inguinal hernias can be reduced nonoperatively. It is recommended to
      repair them in a timely fashion, even in premature infants. Laparoscopic repair
      of incarcerated inguinal hernia repair is considered a safe and effective
      alternative to conventional open herniorrhaphy. Other incarcerated pediatric
      hernias are extremely rare and may be managed effectively with laparoscopy.

PMID- 27894420
TI  - Structural basis for the recognition of spliceosomal SmN/B/B' proteins by the
      RBM5 OCRE domain in splicing regulation.
AB  - The multi-domain splicing factor RBM5 regulates the balance between antagonistic
      isoforms of the apoptosis-control genes FAS/CD95, Caspase-2 and AID. An OCRE
      (OCtamer REpeat of aromatic residues) domain found in RBM5 is important for
      alternative splicing regulation and mediates interactions with components of the
      U4/U6.U5 tri-snRNP. We show that the RBM5 OCRE domain adopts a unique beta-sheet
      fold. NMR and biochemical experiments demonstrate that the OCRE domain directly
      binds to the proline-rich C-terminal tail of the essential snRNP core proteins
      SmN/B/B'. The NMR structure of an OCRE-SmN peptide complex reveals a specific
      recognition of poly-proline helical motifs in SmN/B/B'. Mutation of conserved
      aromatic residues impairs binding to the Sm proteins in vitro and compromises
      RBM5-mediated alternative splicing regulation of FAS/CD95. Thus, RBM5 OCRE
      represents a poly-proline recognition domain that mediates critical interactions
      with the C-terminal tail of the spliceosomal SmN/B/B' proteins in FAS/CD95
      alternative splicing regulation.

PMID- 27894424
TI  - Intestinal Rotation Abnormalities and Midgut Volvulus.
AB  - Rotation abnormalities may be asymptomatic or may be associated with obstruction
      caused by bands, midgut volvulus, or associated atresia or web. The most
      important goal of clinicians is to determine whether the patient has midgut
      volvulus with intestinal ischemia, in which case an emergency laparotomy should
      be done. If the patient is not acutely ill, the next goal is to determine whether
      the patient has a narrow-based small bowel mesentery. In general, the outcomes
      for children with a rotation abnormality are excellent, unless there has been
      midgut volvulus with significant intestinal ischemia.

PMID- 27894425
TI  - Pediatric Testicular Torsion.
AB  - The pediatric patient presenting with acute scrotal pain requires prompt
      evaluation and management given the likelihood of testicular torsion as the
      underlying cause. Although other diagnoses can present with acute testicular
      pain, it is important to recognize the possibility of testicular torsion because
      the best chance of testicular preservation occurs with expeditious management.
      When testicular torsion is suspected, prompt surgical exploration is warranted. A
      delay in surgical management should not occur in an effort to obtain confirmatory
      imaging. When torsion is discovered, the contralateral testicle should undergo
      fixation to reduce the risk of asynchronous torsion.

PMID- 27894426
TI  - Lower Gastrointestinal Bleeding & Intussusception.
AB  - Relatively uncommon compared with the adult population, lower gastrointestinal
      bleeding in children requires expeditious evaluation and management because of
      the variety of causes ranging from benign to life-threatening conditions. The
      causes of lower gastrointestinal bleeding (LGIB) vary with patient age. This
      review focuses on the differential diagnosis and management of LGIB in children.
      Because intussusception is one of the most common sources of LGIB, particular
      attention will be given to its diagnosis and management.

PMID- 27894427
TI  - Overview of Wound Healing and Management.
AB  - Wound healing is a highly complex chain of events, and although it may never be
      possible to eliminate the risk of experiencing a wound, clinicians' armamentarium
      continues to expand with methods to manage it. The phases of wound healing are
      the inflammatory phase, the proliferative phase, and the maturation phase. The
      pathway of healing is determined by characteristics of the wound on initial
      presentation, and it is vital to select the appropriate method to treat the wound
      based on its ability to avoid hypoxia, infection, excessive edema, and foreign
      bodies.

PMID- 27894428
TI  - Pediatric Ovarian Torsion.
AB  - Adnexal torsion is the fifth most common gynecologic emergency. The vague
      clinical presentation and variable imaging findings make the diagnosis difficult.
      If suspicion for adnexal torsion is high enough based on clinical symptoms and
      imaging findings, prompt intervention should include conservative management with
      laparoscopic adnexal detorsion and ovarian preservation even in the event of a
      necrotic-appearing ovary because studies persistently show follicular development
      and ovarian function after a short time period and no increased patient
      morbidity.

PMID- 27894429
TI  - Nonaccidental Trauma in Pediatric Surgery.
AB  - This article presents an overview of nonaccidental trauma in children, including
      common clinical presentation, evaluation, and diagnosis.

PMID- 27894430
TI  - Anesthesia for Common Pediatric Emergency Surgeries.
AB  - Anesthesiologist must be prepared on a daily basis to care for children who need
      emergency surgery. An appropriate perioperative plan must be formulated and
      executed to ensure successful management of the child. This article outlines how
      to prepare and effectively manage common pediatric emergency surgeries.

PMID- 27894431
TI  - Head and Cervical Spine Evaluation for the Pediatric Surgeon.
AB  - This article is designed to guide pediatric surgeons in the evaluation and
      stabilization of blunt head and cervical spine injuries in pediatric patients.
      Trauma remains the number one cause of morbidity and mortality among children,
      and the incidence of head injuries continues to rise. Cervical spine injuries, on
      the other hand, are unusual but can be devastating if missed. This article
      highlights the pathophysiology unique to pediatric head and cervical spine trauma
      as well as keys to clinical and diagnostic evaluation.

PMID- 27894432
TI  - Abdominal Trauma Evaluation for the Pediatric Surgeon.
AB  - Trauma is the leading cause of pediatric mortality and abdominal injury is a
      significant contributor to morbidity. The assessment of abdominal trauma in
      children must be conducted expeditiously and thoroughly. Physical examination,
      laboratory testing, and imaging are central to trauma evaluation. In children
      with minor injury, protocols may help to limit the use of ionizing radiation.
      Children with significant abdominal injury who are unstable should be
      resuscitated with blood products and undergo emergent surgical intervention.

PMID- 27894433
TI  - The Role of Minimally Invasive Surgery in Pediatric Trauma.
AB  - Minimally invasive surgery (MIS) in the management of blunt and penetrating
      pediatric trauma has evolved in the past 30 years. Laparoscopy and thoracoscopy
      possess high levels of diagnostic accuracy with low associated missed injury
      rates. Currently available data advocate limiting the use of MIS to blunt or
      penetrating injuries in the hemodynamically stable child. In the pediatric trauma
      population, MIS offers both diagnostic and therapeutic potential, as well as
      reduced postoperative pain, a decreased rate of postoperative complications,
      shortened hospital stay, and potentially reduced cost.

PMID- 27894434
TI  - Pediatric Airway and Esophageal Foreign Bodies.
AB  - Foreign bodies aspirated into the airway or ingested with retention in the
      esophagus are common in infants and children. Both can cause life-threatening
      complications and must be approached with expeditious diagnosis and definitive
      treatment. Pediatric surgeons should be familiar with diagnosis, treatment,
      operative management, complications, and outcomes of aerodigestive tract foreign
      bodies.

PMID- 27894436
TI  - Foreword.

PMID- 27894437
TI  - Preface.

PMID- 27894435
TI  - Pediatric Appendicitis.
AB  - Appendicitis is one of the most common surgical pathologies in children. It can
      present with right lower quadrant pain. Scoring systems in combination with
      selective imaging and surgical examination will diagnose most children with
      appendicitis. Clinical pathways should be used. Most surgical interventions for
      appendicitis are now almost exclusively laparoscopic, with trials demonstrating
      better outcomes for children who undergo index hospitalization appendectomies
      when perforated. Nonoperative management has a role in the treatment of both
      uncomplicated and complicated appendicitis. This article discusses the workup and
      management, modes of treatment, and continued areas of controversy in pediatric
      appendicitis.

PMID- 27894438
TI  - How Doctors Think: Common Diagnostic Errors in Clinical Judgment-Lessons from an
      Undiagnosed and Rare Disease Program.
AB  - The scientific process of analysis and deduction is frequently, often
      subconsciously, used by physicians to develop a differential diagnosis based on
      patients' symptoms. Common disorders are most frequently diagnosed in general
      practice. Rare diseases are uncommon and frequently remain undiagnosed for many
      years. Cognitive errors in clinical judgment delay definitive diagnosis. Whole
      exome sequencing has helped identify the cause of undiagnosed or rare diseases in
      up to 40% of children. This article provides experiences with an undiagnosed or
      rare disease program, where detailed data accumulation and a multifaceted
      analytical approach assisted in diagnosing atypical presentations of common
      disorders.

PMID- 27894439
TI  - When to Suspect Autoinflammatory/Recurrent Fever Syndromes.
AB  - Autoinflammatory disorders are disorders characterized by rash, arthritis, fever,
      and systemic inflammation. These disorders are caused by mutations in genes
      important in innate immune system sensors. This review highlights the workup of
      an individual with recurrent episodes of inflammation, features of these
      disorders, the genetic defects that cause these disorders, and the specific
      treatments available.

PMID- 27894440
TI  - When Autistic Behavior Suggests a Disease Other than Classic Autism.
AB  - Most neurodevelopmental disorders are defined by their clinical symptoms and many
      disorders share common features. Recently there has been an increase in the
      number of children diagnosed with autism spectrum disorder, although concerns
      have been raised about the accuracy of the reported prevalence rates. This
      article reviews the essential features of autism spectrum disorder and describes
      other conditions that may include similar symptoms that may be misdiagnosed as
      autism spectrum disorder (primary communication disorders, anxiety disorders,
      attachment disorders, intellectual disability, vision and hearing impairment, and
      normal variations). An approach to differential diagnosis is discussed with
      particular attention to evaluation of young children.

PMID- 27894441
TI  - Nonclassic Inflammatory Bowel Disease in Young Infants: Immune Dysregulation,
      Polyendocrinopathy, Enteropathy, X-Linked Syndrome, and Other Disorders.
AB  - This article discusses non-classical forms of inflammatory bowel disease (IBD)
      mainly occurs in infants and very young children. Defects in every aspect of the
      immune system, such as neutrophils, T-cell and B-cell lymphocytes, and
      macrophages are associated with IBD in infants. Also, non lympho-hematopoietic
      defects with primary defects in enterocytes can also lead to IBD-like
      manifestations. Clinical vignettes are presented and the genetic origins and
      possible management strategies are outlined. Early evaluation of these patients
      is important because identification of underlying immune defects would facilitate
      the use of better-targeted therapy for the specific genetic defect.

PMID- 27894442
TI  - Presentation and Diagnostic Evaluation of Mitochondrial Disease.
AB  - Mitochondrial disease (MD) occurs when alteration of mitochondrial respiratory
      chain complex function caused by genetic mutation produces a detectable disease
      state. These mutations may be found in either the nuclear or mitochondrial
      genomes, and may only be present in a subset of cells or body tissues. Thus, the
      phenotype of MD is extremely variable and the definitive diagnosis of MD is
      complex. This article provides a brief description of a strategy used in the
      diagnosis of MD, by integrating data from clinical, imaging, pathologic,
      molecular, and enzymatic assessments. Additional information on characteristic
      findings seen in classic MD syndromes is also provided.

PMID- 27894443
TI  - The Team-Based Approach to Undiagnosed and Rare Diseases.
AB  - Patients with undiagnosed or rare diseases often remain without a diagnosis for
      many years. Many are misdiagnosed or treated symptomatically without having an
      identified underlying disease process. Health care providers in general practice
      and subspecialists are equipped to diagnose diseases commonly seen. Most
      practitioners are unlikely to be familiar with uncommon manifestations of a
      common disorder and have little or no experience with rare diseases.
      Multidisciplinary teams are effective in reviewing patients with undiagnosed and
      rare diseases and in developing a new diagnostic strategy for appropriate
      evaluation. A medical librarian and an access coordinating navigator are
      essential members of the team.

PMID- 27894444
TI  - Unusual Structural Autonomic Disorders Presenting in Pediatrics: Disorders
      Associated with Hypoventilation and Autonomic Neuropathies.
AB  - Structural autonomic disorders (producing structural damage to the autonomic
      nervous system or autonomic centers) are far less common than functional
      autonomic disorders (reflected in abnormal function of a fundamentally normal
      autonomic nervous system) in children and teenagers. This article focuses on this
      uncommon first group in the pediatric clinic. These disorders are grouped into 2
      main categories: those characterized by hypoventilation and those that feature an
      autonomic neuropathy.

PMID- 27894445
TI  - Usual and Unusual Manifestations of Systemic and Central Nervous System
      Vasculitis.
AB  - The idiopathic vasculitides are a group of inflammatory and immune-mediated
      conditions associated with inflammation of blood vessels. They affect multiple
      organ and body systems, and vary in their clinical manifestations, severity,
      prognosis, and pathology. They frequently present a diagnostic challenge for
      clinicians because of their complexity, overlapping features, and similar
      findings to other noninflammatory, genetic, or infectious conditions. This
      article summarizes some of the common pediatric vasculitides, emphasizing both
      the characteristic and unusual clinical manifestations of these diseases.

PMID- 27894448
TI  - The Intersection of Medical Child Abuse and Medical Complexity.
AB  - Children with medical complexity and victims of medical child abuse may have
      similar clinical presentations. Atypical or unexplained signs and symptoms due to
      rare diseases may lead providers to suspect medical child abuse when not present.
      Conversely, medical child abuse may be the cause of or coexist with medical
      complexity. Careful consideration of whether or not medical child abuse is
      present is essential when assessing a child with medical complexity since either
      diagnosis has significant consequences for children and families.

PMID- 27894446
TI  - Fever of Unknown Origin in Childhood.
AB  - Childhood fever of unknown origin (FUO) is most often related to an underlying
      infection but can also be associated with a variety of neoplastic, rheumatologic,
      and inflammatory conditions. Repeated, focused reviews of patient history and
      physical examination are often helpful in suggesting a likely diagnosis.
      Diagnostic workup should be staged, usually leaving invasive testing for last.
      Advances in molecular genetic techniques have increased the importance of these
      assays in the diagnosis of FUO in children.

PMID- 27894447
TI  - Differentiating Familial Neuropathies from Guillain-Barre Syndrome.
AB  - Differentiating Guillain-Barre syndrome (GBS) from inherited neuropathies and
      other acquired peripheral neuropathies requires understanding the atypical
      presentations of GBS and its variant forms, as well as historical and physical
      features suggestive of inherited neuropathies. GBS is typically characterized by
      the acute onset of ascending flaccid paralysis, areflexia, and dysesthesia
      secondary to peripheral nerve fiber demyelination. The disorder usually arises
      following a benign gastrointestinal or respiratory illness, is monophasic,
      reaches a nadir with several weeks, and responds to immunomodulatory therapy.
      Inherited neuropathies with onset before adulthood, whose presentation may mimic
      Guillain-Barre syndrome, are reviewed.

PMID- 27894449
TI  - Ending a Diagnostic Odyssey: Family Education, Counseling, and Response to
      Eventual Diagnosis.
AB  - Genomic sequencing is the diagnostic test of choice for families with undiagnosed
      or rare diseases seeking an explanation for their child's complex medical
      concerns. The desire to find answers can easily bias interpretation of sequencing
      results, and thus the counseling process is designed to facilitate informed
      decision making and set realistic expectations for possible outcomes. The patient
      case examples serve to highlight the various challenges and complexities
      encountered with the clinical application of genomic sequencing and to reflect
      some of the data that has been accrued during the past 5 years of clinical
      experience.

PMID- 27894450
TI  - Immunodeficiency Presenting as an Undiagnosed Disease.
AB  - Although primary immunodeficiencies typically present with recurrent, chronic, or
      severe infections, autoimmune manifestations frequently accompany these disorders
      and may be the initial clinical manifestations. The presence of 2 or more
      autoimmune disorders, unusual severe atopic disease, or a combination of these
      disorders should lead a clinician to consider primary immunodeficiency disorders.

PMID- 27894451
TI  - Eczema and Urticaria as Manifestations of Undiagnosed and Rare Diseases.
AB  - Eczema and urticaria are common disorders encountered in pediatric patients, but
      they may occasionally be the presenting complaint in a child with an underlying
      rare disease. Immunodeficiency syndromes should be suspected when eczema is
      associated with neonatal onset, recurrent infections, chronic lymphadenopathy, or
      failure to thrive. Nutritional deficiencies and mycosis fungoides are in the
      differential diagnosis for a child with a recalcitrant eczematous eruption.
      Autoinflammatory syndromes should be suspected in a child with chronic urticaria,
      fever, and other systemic signs of inflammation. Although these disorders are
      rare, early recognition allows for appropriate treatment and decreased morbidity
      for the child.

PMID- 27894452
TI  - Immune-Mediated Diseases of the Central Nervous System: A Specificity-Focused
      Diagnostic Paradigm.
AB  - Immune-mediated diseases of the central nervous system show wide variability both
      symptomatically and with respect to underlying pathophysiology. Recognizing
      aberrant immunologic activity as the cause of neurologic dysfunction requires
      establishing as precise a neuroanatomic and functional phenotype as possible, and
      a diagnostic and therapeutic strategy that stabilizes the patient, excludes broad
      categories of disease via rapidly available diagnostic assays, and maintains a
      broad differential diagnosis that includes immune-mediated conditions. This
      process is aided by recognizing the appropriate clinical circumstances under
      which immune-mediated disease should be suspected, and how to differentiate these
      conditions from other causes of similar neurologic dysfunction.

PMID- 27894454
TI  - Undiagnosed and Rare Childhood Diseases.

PMID- 27894455
TI  - Undiagnosed and Rare Diseases.

PMID- 27894453
TI  - Usual and Unusual Manifestations of Familial Hemophagocytic Lymphohistiocytosis
      and Langerhans Cell Histiocytosis.
AB  - Familial hemophagocytic lymphohistiocytosis (FHL) and Langerhans cell
      histiocytosis (LCH) are histiocytic diseases that occur most commonly in young
      children. Improvements in recognition and treatment have been substantial for
      both diseases in the past decade, although early and late morbidity continue to
      be major concerns. These two diagnoses behave differently, although the clinical
      spectra for both diseases are diverse and can lead to confusion and delays in
      diagnosis and treatment. This article focuses on the clinical and genetic
      spectrum of FHL as well as the clinical and treatment variations of LCH.

PMID- 27894456
TI  - A systematic review and meta-analysis of the effort-reward imbalance model of
      workplace stress with indicators of immune function.
AB  - OBJECTIVE: Despite considerable research into associations between the effort
      reward imbalance (ERI) model and various health outcomes over the past 20years,
      the underlying mechanisms responsible for the association remain unclear.
      Recently, ERI investigations have examined associations with immune sub-systems
      (e.g., leukocytes, cytokines and immunoglobulins). Synthesis of the amalgamated
      research evidence will aid clarity to this field of enquiry. We conducted a meta
      analysis and reviewed the associations of ERI and over-commitment (OC) in the
      workplace with immunity. METHOD: Electronic databases were searched with the
      phrase 'effort reward imbalance' which initially yielded 319 studies leading to
      57 full text studies being screened. Seven studies that met inclusion criteria
      were combined using mixed and random effects models. RESULTS: Greater ERI was
      associated with lower immunity (r=-0.09, CI -0.14, -0.05, p<0.001). Sub-group
      analyses revealed the effect with mucosal immunity was stronger (r=-0.33, CI 
      0.47 to -0.18) than trends between both cytokine (r=-0.04, CI -0.07, -0.01) and
      leukocyte sub-groups (r=-0.02 CI -0.04, 0.01) respectively (k=7, N=9952). Over
      commitment was also associated with lower immunity (r=-0.05, CI -0.09, 0.01,
      p=0.014); subgroup (leukocytes, cytokines, mucosal immunity) associations,
      however, were homogenous (Q=1.83, df=2, p=0.400, k=6, N=2358). CONCLUSIONS:
      Greater ERI and OC were both associated with lower immunity. The association
      between mucosal immunity and ERI was stronger than the cytokine and leukocyte sub
      groups. OC moderated the relationship between ERI and immunity.

PMID- 27894457
TI  - Reliability and validity of the coping strategy inventory-short form applied to
      hemodialysis patients in 13 countries: Results from the Dialysis Outcomes and
      Practice Patterns Study (DOPPS).
AB  - OBJECTIVES: The Coping Strategies Inventory-Short Form (CSI-SF) measures four
      coping strategies based on 16 items: 4 items each indicating problem- vs. emotion
      focused engagement or disengagement. Here we provide the first assessment of
      reliability and construct validity of the CSI-SF among hemodialysis patients
      across 13 countries. METHODS: The CSI-SF was completed by patients in 9 languages
      in phase 4 of the Dialysis Outcomes and Practice Patterns Study (2009-11).
      Cronbach's alpha was used to assess internal consistency. Exploratory and
      confirmatory factor analyses were applied to assess the factor structure of the
      CSI-SF by country and language. CSI-SF data were analyzed from 7201 patients (60%
      male; median age 62.5 [range 18-96] years). RESULTS: Good internal consistency
      (alpha=0.56-0.80) was seen for three scales in English (US, UK, Canada,
      Australia, New Zealand), German, and Swedish versions. The fourth scale was
      internally consistent if two items were dropped. In these countries, both
      exploratory and confirmatory factor analyses indicated a factor structure
      consistent with the four CSI-SF scales. Other language versions showed a factor
      structure inconsistent with these four scales. CONCLUSION: The slightly modified
      English, German, and Swedish versions of the CSI-SF are reliable and valid
      instruments for measuring coping strategies in hemodialysis patients.

PMID- 27894458
TI  - Personality and global cognitive decline in Japanese community-dwelling elderly
      people: A 10-year longitudinal study.
AB  - OBJECTIVES: To examine the longitudinal associations between the big five
      personality and changes in global cognitive function among community-dwelling
      elderly people involved in the National Institute for Longevity Sciences -
      Longitudinal Study of Aging. METHODS: The participants were 594 individuals (age
      range 60-81years) and followed for 10years and tested six times. Personality was
      assessed by the Japanese version of NEO five factor inventory at baseline.
      Cognitive function was assessed by the Japanese version of Mini Mental State
      Examination (MMSE) at all visits. For participants with a baseline MMSE
      score>=28, logistic generalized estimating equation models estimated the odds
      ratio (OR) and 95% confidence interval (CI) for MMSE score<=27 at each follow-up
      visit, according to a 1-SD increase of the baseline personality score. Post hoc
      analyses were performed for mild cognitive deficits, baseline MMSE score>=24 and
      <=27, to estimate the OR and CI for MMSE score<=23. RESULTS: The adjusted OR for
      MMSE score<=27 was 0.78 (95% CI, 0.69-0.88), with a 1-SD increase in Openness to
      Experience score. In post hoc analyses, the adjusted OR for MMSE score<=23 was
      0.50 (95% CI, 0.35-0.72) with a 1-SD increase in Conscientiousness score.
      Relationships between other personality traits and the decline in MMSE score were
      not significant. CONCLUSIONS: Higher Openness to Experience was associated with a
      reduction in risk for cognitive decline in community-dwelling older adults.
      Higher Conscientiousness might also predict lower risk for severe cognitive
      decline, especially for individuals with mild cognitive deficits.

PMID- 27894459
TI  - DSM-5 somatic symptom disorder in patients with vertigo and dizziness symptoms.
AB  - OBJECTIVE: DSM-5 somatic symptom disorder (SSD) could potentially be a highly
      relevant diagnosis for patients with vertigo and dizziness. The criteria of SSD,
      particularly the B-criterion with its three components (cognitive, affective,
      behavioral), have however not yet been investigated in this patient group.
      METHODS: We evaluated a large sample (n=399) of outpatients presenting in a
      neurological setting. Physical examinations and a psychometric assessment (SCID
      I) were conducted; patients completed self-report questionnaires. The diagnosis
      of SSD was assigned retrospectively. The prevalence of SSD, its diagnostic
      criteria, and its overlap with former DSM-IV somatoform disorders were evaluated;
      comparisons were drawn between (1) patients fulfilling different components of
      the B-criterion and (2) patients with diagnoses after DSM-IV vs. DSM-5. RESULTS:
      SSD was almost twice as common as DSM-IV somatoform disorders. Patients with all
      three components of the B-criterion reported the highest impairment levels.
      Patients with both DSM-IV somatoform disorders and DSM-5 SSD were more impaired
      compared to groups with one of the diagnoses; patients with DSM-IV somatoform
      disorders only were more impaired than those with SSD only. CONCLUSIONS: Our
      findings demonstrate that SSD is highly prevalent in patients with vertigo and
      dizziness. The classification of severity based on the number of psychological
      symptoms appears valid and may assist in finding suitable treatment options
      according to clinical practice guidelines. Future studies should investigate the
      overlap of SSD and other psychiatric disorders, this may assist in better
      defining the diagnostic criteria of SSD.

PMID- 27894460
TI  - The mediation effect of health literacy between subjective social status and
      depressive symptoms in patients with heart failure.
AB  - OBJECTIVES: Depressive symptoms are prevalent and cause adverse outcomes in heart
      failure. Previous studies have linked depressive symptoms with socioeconomic
      status. However, little is known about the mechanisms underlying this
      relationship. This study aimed to evaluate the association between socioeconomic
      status and depressive symptoms, and to examine whether access to healthcare,
      health literacy and social support mediated this relationship in patients with
      heart failure. METHODS: Cross-sectional design was used to study 321 patients
      with heart failure recruited from a general hospital. Demographics, clinical
      data, depressive symptoms, socioeconomic status (i.e., education, employment,
      income, and subjective social status), access to healthcare, health literacy, and
      social support were collected by patient interview, medical record review or
      questionnaires. A series of logistic regressions and linear regressions were
      conducted to examine mediation. RESULTS: The mean age of patients with heart
      failure was 63.6+/-10.6years. Fifty-eight patients (18%) had depressive symptoms.
      Lower subjective social status (OR=1.321, p=0.012) and lower health literacy
      (OR=1.065, p<0.001) were separately associated with depressive symptoms. When
      subjective social status and health literacy were entered simultaneously, the
      relationship between subjective social status and depressive symptoms became non
      significant (OR=1.208, p=0.113), demonstrating mediation. Additionally, lower
      social support was associated with depressive symptoms (OR=1.062, p=0.007).
      CONCLUSIONS: In patients with heart failure, health literacy mediated the
      relationship between subjective social status and depressive symptoms. Lower
      social support was associated with depressive symptoms. Interventions should take
      these factors into account.

PMID- 27894461
TI  - Does Mindfulness-Based Cognitive Therapy benefit all people with diabetes and
      comorbid emotional complaints equally? Moderators in the DiaMind trial.
AB  - OBJECTIVES: Research has shown the effectiveness of mindfulness-based
      interventions for a variety of emotional problems in different samples, but it is
      unknown which factors influence this effectiveness. Therefore, the aim of the
      current study was: which factors (demographic, personality, and baseline levels
      of mindfulness skills) moderate the effectiveness of Mindfulness-Based Cognitive
      Therapy (MBCT)? METHODS: Outpatients with diabetes (type 1 or type 2; N=139) and
      an elevated level of emotional distress participated in the Diabetes and
      Mindfulness (DiaMind) trial. They were randomized into MBCT (N=70) or a control
      group (N=69) that received treatment as usual and that was offered the
      intervention 6months later. Primary outcomes were anxiety, depressive symptoms,
      and perceived stress at post-intervention and at 6-month follow-up. RESULTS:
      Mixed models analyses showed that sex, extraversion, and baseline acting with
      awareness were significant moderators of effectiveness. In the MBCT group, women
      showed larger decreases in anxiety and depression across time (large effects)
      compared to men (medium to small effects). For extraversion divided into
      quartiles, the three lowest quartiles generally exhibited large decreases in
      symptoms, whereas the high extraversion group showed medium (perceived stress) to
      small (depression) decreases. CONCLUSION: MBCT seems to be effective to decrease
      symptoms of anxiety, depression, and perceived stress for a broad range of person
      characteristics in patients with diabetes. However, men and those high in
      extraversion showed considerably lower effectiveness compared to the other
      groups. The small effect in high extraverts may be due to the large dropout in
      this subgroup.

PMID- 27894463
TI  - What should we say to patients with unexplained neurological symptoms? How
      explanation affects offence.
AB  - OBJECTIVES: Unexplained neurological symptoms (UNS) are common presentations in
      neurology but there is no consensus as to what they should be called. This is
      important, as patient acceptance is a predictor of outcome and there is evidence
      that patients are unhappy with the terms used. Patient understanding of these
      terms may be limited, however, and, once explained, the terms may seem more or
      less offensive. We sought to elicit patients' views of 7 frequently used terms
      for UNS, and whether these changed once definitions were provided. METHODS: 185
      participants were recruited from a medical outpatients' waiting area. They were
      given questionnaires outlining a hypothetical situation of leg weakness, with 7
      possible labels. Participants were asked whether they endorsed 4 connotations for
      each label and the "number needed to offend" (NNO) calculated, before and after
      definitions were given. RESULTS: It was found that "functional" was significantly
      less offensive than other terms used (NNO 17, compared with "Conversion Disorder"
      NNO 5, p<0.001). Reported understanding of the terms was generally low, however,
      and many terms became significantly more offensive once definitions were
      provided. Participants' reported understanding had a significant effect, with low
      understanding causing terms to be viewed as more offensive after explanation.
      CONCLUSION: Much of the 'offence' in UNS lies not in the terminology but in the
      meaning those terms carry. This study replicated previous findings that
      "functional" was less offensive than other terms, even after explanation, but in
      common with most terms this was partly due to patients' limited understanding of
      its meaning.

PMID- 27894462
TI  - Multiple somatic symptoms in primary care: A field study for ICD-11 PHC, WHO's
      revised classification of mental disorders in primary care settings.
AB  - OBJECTIVE: A World Health Organization (WHO) field study conducted in five
      countries assessed proposals for Bodily Stress Syndrome (BSS) and Health Anxiety
      (HA) for the Primary Health Care Version of ICD-11. BSS requires multiple somatic
      symptoms not caused by known physical pathology and associated with distress or
      dysfunction. HA involves persistent, intrusive fears of having an illness or
      intense preoccupation with and misinterpretation of bodily sensations. This study
      examined how the proposed descriptions for BSS and HA corresponded to what was
      observed by working primary care physicians (PCPs) in participating countries,
      and the relationship of BSS and HA to depressive and anxiety disorders and to
      disability. METHOD: PCPs referred patients judged to have BSS or HA, who were
      then interviewed using a standardized psychiatric interview and a standardized
      measure of disability. RESULTS: Of 587 patients with BSS or HA, 70.4% were
      identified as having both conditions. Participants had an average of 10.9 somatic
      symptoms. Patients who presented somatic symptoms across multiple body systems
      were more disabled than patients with symptoms in a single system. Most referred
      patients (78.9%) had co-occurring diagnoses of depression, anxiety, or both.
      Anxious depression was the most common co-occurring psychological disorder,
      associated with the greatest disability. CONCLUSION: Study results indicate the
      importance of assessing for mood and anxiety disorders among patients who present
      multiple somatic symptoms without identifiable physical pathology. Although
      highly co-occurring with each other and with mood and anxiety disorders, BSS and
      HA represent distinct constructs that correspond to important presentations in
      primary care.

PMID- 27894464
TI  - Functional neurological symptoms modulate processing of emotionally salient
      stimuli.
AB  - OBJECTIVE: Dysfunctional emotion processing has been discussed as a contributing
      factor to functional neurological symptoms (FNS) in the context of conversion
      disorder, and refers to blunted recognition and the expression of one's own
      feelings. However, the emotion processing components characteristic for FNS
      and/or relevant for conversion remain to be specified. With this goal, the
      present study targeted the initial, automatic discrimination of emotionally
      salient stimuli. METHODS: The magnetoencephalogram (MEG) was monitored in 21
      patients with functional weakness and/or sensory disturbance subtypes of FNS and
      21 healthy comparison participants (HC) while they passively watched 600
      emotionally arousing, pleasant, unpleasant or neutral stimuli in a rapid serial
      visual presentation (RSVP) design. Neuromagnetic activity was analyzed 110-330ms
      following picture onset in source space for prior defined posterior and central
      regions of interest. RESULTS: As early as 110ms and across presentation interval,
      posterior neural activity modulation by picture category was similar in both
      groups, despite smaller initial (110-150ms) overall and posterior power in
      patients with FNS. The initial activity modulation by picture category was also
      evident in the left sensorimotor area in patients with FNS, but not significant
      in HC. CONCLUSIONS: Similar activity modulation by emotional picture category in
      patients with FNS and HC suggests that the fast, automatic detection of emotional
      salience is unchanged in patients with FNS, but involves an emotion-processing
      network spanning posterior and sensorimotor areas.

PMID- 27894465
TI  - Is denial a maladaptive coping mechanism which prolongs pre-hospital delay in
      patients with ST-segment elevation myocardial infarction?
AB  - OBJECTIVE: During an acute myocardial infarction, patients often use denial as a
      coping mechanism which may provide positive mood regulating effects but may also
      prolong prehospital delay time (PHD). However, empirical evidences are still
      sparse. METHODS: This cross-sectional study included 533 ST-elevated myocardial
      infarction (STEMI) patients from the Munich Examination of Delay in Patients
      Experiencing Acute Myocardial Infarction (MEDEA) study. Data on sociodemographic,
      clinical and psycho-behavioral characteristics were collected at bedside. The
      outcome was assessed using the Cardiac Denial of Impact Scale (CDIS) with the
      median split as cutoff point. A total of 206 (41.8%) STEMI patients were thus
      classified as deniers. RESULTS: Deniers were less likely to suffer from major
      depression (p=0.04), anxiety (p=0.01) and suboptimal well-being (p=0.01) compared
      to non-deniers during the last six months prior to STEMI. During STEMI, they were
      less likely to perceive severe pain strength (p=0.04) and racing heart (p=0.02).
      Male deniers were also less likely to perceive shortness of breath (p=0.03) and
      vomiting (p=0.01). Denial was not associated with overall delay time. However, in
      the time window of 3 to 24h, denial accounted for roughly 40min extra delay (356
      vs. 316.5min p=0.02 n=196). CONCLUSIONS: Denial not only contributes to less
      suffering from acute heart related symptoms and negative affectivity but also
      leads to a clinically significant delay in the prevalent group.

PMID- 27894466
TI  - Relationships between adult emotional states and indicators of health care
      utilization: Findings from the National Health Interview Survey 2006-2014.
AB  - OBJECTIVE: Adults with serious psychological distress have a high likelihood of
      mental health problems severe enough to cause serious impairment in social and
      occupational functioning requiring treatment. These adults visit doctors
      frequently yet have poor health compared to adults without serious psychological
      distress. This study examined associations between emotional states of serious
      psychological distress in relationship to healthcare utilization indicators. A
      guiding hypothesis was that somatization underlying emotional states contributes
      to excessive healthcare seeking among adults with serious psychological distress.
      METHODS: Using 2006-2014 National Health Interview Survey, in adults with serious
      psychological distress (n=9271), the six states: unable to make efforts,
      nervousness, hopelessness, sadness, worthlessness and restlessness were assessed
      in multivariate models in relation to four healthcare utilization indicators:
      change in the usual place of healthcare, change due to insurance, having seen a
      healthcare provider in the last 6months and having 10 or more doctor visits in
      the last 12months. Models were adjusted for sociodemographic variables, having
      seen a mental health provider, and health conditions. RESULTS: Adults feeling
      unable to make efforts were more likely to seek healthcare in the last 6months
      and at least ten times in the last twelve months. Adults feeling hopeless were
      less likely to be heavy healthcare utilizers. CONCLUSIONS: Predisposing medical
      conditions do not fully explain healthcare utilization in adults with serious
      psychological distress. Educating healthcare providers about the emotional states
      motivating healthcare seeking, and integrating mental healthcare into primary
      care, may improve the health of adults with serious psychological distress.

PMID- 27894467
TI  - Association between hair cortisol concentration and perceived stress in female
      methamphetamine addicts.
AB  - OBJECTIVE: The present study aims to explore whether hair cortisol concentration
      is associated with explicit stress or implicit stress in female methamphetamine
      addicts. METHODS: Hair samples were collected from 51 female methamphetamine
      addicts from inpatient addiction treatment programs. Perceived stress was
      assessed by both explicit and implicit measures through the Perceived Stress
      Scale (PSS) and the Implicit Association Test (IAT), respectively. RESULTS: The
      positive relationship between hair cortisol concentration with D-scores of the
      IAT reached statistically significant difference. A marginal correlation between
      hair cortisol concentration and scores of the PSS was observed. Additionally,
      linear regression analysis indicated that D-scores of the IAT are strongly
      predictive of hair cortisol concentration. CONCLUSION: Hair cortisol
      concentration is strongly related to implicit stress but only weakly related with
      explicit stress.

PMID- 27894468
TI  - Exploring an association between hostility and serum concentrations of TNF-alpha
      and its soluble receptors.

PMID- 27894469
TI  - The association of perseverative negative thinking with depression, anxiety and
      emotional distress in people with long term conditions: A systematic review.
AB  - OBJECTIVE: Depression is common in people with long term conditions, and is
      associated with worse medical outcomes. Previous research shows perseverative
      negative thinking (e.g. worry, rumination) predicts subsequent depression and
      worse medical outcomes, suggesting interventions targeting perseverative negative
      thinking could improve depression and medical outcomes. Previous studies
      recruited healthy individuals, however. This review aimed to determine the
      temporal relationship and strength of prospective association of perseverative
      negative thinking with depression, anxiety and emotional distress in people with
      long term conditions. METHOD: Four electronic databases were searched for studies
      including standardised measures of perseverative negative thinking and
      depression, anxiety or emotional distress, and which presented prospective
      associations. Findings were narratively synthesized. RESULTS: Thirty studies were
      identified in a range of long term conditions. Perseverative negative thinking
      and subsequent depression, anxiety or emotional distress were significantly
      correlated in the majority of studies (bivariate r=0.23 to r=0.73). 25 studies
      controlled for confounders, and in 15 perseverative negative thinking predicted
      subsequent depression, anxiety or emotional distress. Results varied according to
      condition and study quality. Six of 7 studies found bivariate associations
      between depression, anxiety or emotional distress and subsequent perseverative
      negative thinking, though 2 studies controlling for key covariates found no
      association. Few studies assessed the impact of perseverative negative thinking
      on medical outcomes. CONCLUSION: Strongest evidence supported perseverative
      negative thinking predicting subsequent depression, anxiety and emotional
      distress in people with long term conditions. Further prospective research is
      warranted to clarify the association of perseverative negative thinking with
      subsequent poor medical outcomes.

PMID- 27894471
TI  - ?

PMID- 27894470
TI  - Effectiveness of a placebo intervention on visually induced nausea in women - A
      randomized controlled pilot study.
AB  - OBJECTIVE: Improvement of nausea by placebo interventions has recently been
      demonstrated in clinical trials and experimental settings. However, many
      questions regarding placebo effects on nausea remain unanswered. For example,
      nausea reduction in women could only be achieved when the placebo intervention
      was "enhanced" by conditioning, while men responded primarily to verbally
      suggested improvement. It is unclear whether these findings are generalizable or
      were due to situational variables. In this pilot study, we investigated the
      effects of sham acupuncture point stimulation and verbal suggestions on visually
      induced nausea in a female population. METHODS: In a within-subjects design, 21
      healthy female volunteers underwent both a placebo condition and a natural
      history condition (control condition) in a randomized order on two separate days.
      On both days, nausea was induced through optokinetic stimulation. On the placebo
      day, participants received sham acupuncture point stimulation together with
      positive verbal suggestions of nausea improvement. Expected and perceived nausea
      severity as well as symptoms of motion sickness were repeatedly assessed.
      RESULTS: Twenty participants completed both testing days. Participants developed
      significantly less nausea on the placebo day compared to the control day
      (p<0.001), and the effect size of placebo-induced nausea reduction was large
      (partial eta2=0.71). Symptoms of motion sickness were also reduced (p=0.003).
      Expectation of nausea decreased following the placebo intervention as compared to
      no treatment (p=0.030), indicating successful expectancy manipulation.
      CONCLUSION: Sham acupuncture point stimulation combined with verbal suggestions
      induced a significant placebo effect on visually-induced nausea in women.

PMID- 27894472
TI  - [Long-term intravenous devices, continuity of care from the specialist doctor to
      the nurse].
AB  - Long-term intravenous devices have become an essential tool in the treatment of
      patients requiring the administration of medication over more than one month. The
      choice of device must be established through consultation between the nursing
      team and the patient. Several types of complications can be observed immediately
      after the insertion of the device and during treatment. Protocols in the
      community and at hospital are therefore necessary in order that doctors, nurses,
      specialists and experts work together. Clinical and translational research should
      enable the incidence of certain complications, notably infections and thrombosis,
      to be further reduced.

PMID- 27894473
TI  - ?

PMID- 27894474
TI  - [Telemedicine in current nursing practices].
AB  - The first priority telemedicine programme focused, from 2011, on five areas, with
      the aim of guaranteeing equal access to care to everybody across a healthcare
      region. Experiments were financed by public authorities. These practices are now
      integrated into the organisation of healthcare.

PMID- 27894475
TI  - [Telemedicine in France, from the concept to practice].
AB  - The implementation of telemedicine has drawn on numerous innovative initiatives
      and has required a legal framework to be established. Today, the various uses of
      this valuable 'connected tool' can be appropriated in order to improve access to
      care. It also improves cooperation between healthcare professionals scattered
      across the health region.

PMID- 27894476
TI  - [Telemedicine and new forms of cooperation between doctors and caregivers].
AB  - The development of telemedicine is accompanied by new forms of coordination and
      cooperation between doctors and paramedical caregivers. If we consider the work
      in terms of the way it is actually carried out in practice, we have a better
      understanding of the efforts made by practitioners to adapt, as well as the
      challenges associated with the integration of telemedicine systems. These effect
      the notions and the execution of 'good work'.

PMID- 27894478
TI  - [The use of telemedicine in dialysis and new professional practices].
AB  - Since 2006, a remote patient monitoring scheme using digital pens has enabled
      patients with chronic kidney disease to be monitored remotely in their own home.
      The implementation of this project was accompanied by a technical and economic
      study. Today, this scheme has evolved to integrate therapeutic patient education
      programmes and their evaluation.

PMID- 27894477
TI  - [Telemedicine, cementing the nursing team].
AB  - Communication technologies have an impact on our healthcare system. We care for
      human beings in an environment which is now digital and which influences their
      experience, their treatment and their perception of their disease. Telemedicine
      will become a key tool for all caregivers. It has no bearing on nurses' skills,
      but changes the way care is organised, for the benefit of patients as well as
      healthcare professionals.

PMID- 27894479
TI  - [The benefit of telemedicine for enabling elderly or disabled people to access
      care].
AB  - In 2013, a convalescence and care home carried out a telemedicine experiment in
      order to favour access to care for elderly and/or disabled people. In this
      context, in accordance with regulations, the team carried out an assessment of
      the project by studying the added value of this tool, its limits, as well as the
      initial effects on the residents and the practices of the healthcare
      professionals.

PMID- 27894480
TI  - [Cardiauvergne is a remote monitoring and care coordination service for patients
      with severe heart failure].
AB  - Since 2011, thanks to the cooperation of frontline healthcare professionals, it
      has provided care to more than 1 200 patients across the Auvergne health region.
      The organisation, blending telemedicine and human contact, has made this
      initiative a successful example of how the boundaries between community and
      hospital healthcare can be removed.

PMID- 27894481
TI  - [Telemedicine in hospital at home care].
AB  - A telemedicine project in a rehabilitation centre has been developed in the
      framework of hospital at home care, for patients discharged early after surgery.
      This project is the subject of a medico-economic study in cooperation with the
      Regional Healthcare Agency in order to assess its impact. The results are
      promising and herald major changes in the care pathway of patients cared for in
      the home, as digital technologies continue to develop.

PMID- 27894482
TI  - [The remote monitoring of chronic wounds treated in the home].
AB  - The Franche-Comte Regional Health Authority, in collaboration with the chronic
      wound outpatient centre of Besancon university hospital and twelve volunteer
      sites, has developed a remote patient monitoring programme for monitoring chronic
      wounds in the home. It has been used by private practice nurses since 2009.

PMID- 27894483
TI  - [Telepsychiatry and cooperation between professionnals in a mobile team].
AB  - Telepsychiatry in a mobile team uses advanced technology for the benefit of
      healthcare. It requires a high level of cooperation between the different
      players. In a nursing home, ilt provides patients with access to psyhiatric care
      despite the distance or the difficulties involved in travelling to an
      appointment.

PMID- 27894484
TI  - [Nursing care in telemedicine and telehealth across the world].
AB  - Developments in cyberhealth are now accessible to all patients and healthcare
      professionals. These tools enable expert advice to be provided remotely and
      ensure a continuity of care for all those who need it. Telecare is developing
      across the world, as are networks of nurses who practise it and researchers who
      analyse the results.

PMID- 27894485
TI  - ?

PMID- 27894487
TI  - 2016 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart
      Failure.

PMID- 27894491
TI  - Coagulopathy of Trauma.
AB  - Coagulopathy is common after injury and develops independently from iatrogenic,
      hypothermic, and dilutional causes. Despite considerable research on the topic
      over the past decade, trauma-induced coagulopathy (TIC) continues to portend poor
      outcomes, including decreased survival. We review the current evidence regarding
      the diagnosis and mechanisms underlying trauma induced coagulopathy and summarize
      the debates regarding optimal management strategy including product
      resuscitation, potential pharmacologic adjuncts, and targeted approaches to
      hemostasis. Throughout, we will identify areas of continued investigation and
      controversy in the understanding and management of TIC.

PMID- 27894486
TI  - Comments on the 2016 ESC Guidelines for the Diagnosis and Treatment of Acute and
      Chronic Heart Failure.

PMID- 27894490
TI  - Traumatic Brain Injury Advances.
AB  - There have been many recent advances in the management of traumatic brain injury
      (TBI). Research regarding established and novel therapies is ongoing. Future
      research must not only focus on development of new strategies but determine the
      long-term benefits or disadvantages of current strategies. In addition, the
      impact of these advances on varying severities of brain injury must not be
      ignored. It is hoped that future research strategies in TBI will prioritize large
      scale trials using common data elements to develop large registries and
      databases, and leverage international collaborations.

PMID- 27894493
TI  - Optimal Reversal of Novel Anticoagulants in Trauma.
AB  - The incidence of patients with trauma on novel oral anticoagulants (NOACs) for
      the treatment of thromboembolic disorders is increasing. In severe bleeding or
      hemorrhage into critical spaces, urgent reversal of this underlying pharmacologic
      coagulopathy becomes paramount. Optimal reversal strategy for commonly used NOACs
      is still evolving. Basic tenets of evaluation of patients with trauma and
      resuscitation remain the same. Clinical outcomes data in bleeding human patients
      with trauma are lacking, but are needed to establish efficacy and safety in these
      treatments. This article summarizes the available evidence and provides the
      optimal reversal strategy for bleeding patients with trauma on NOACs.

PMID- 27894492
TI  - Management of Trauma-Induced Coagulopathy with Thrombelastography.
AB  - Viscoelastic assays, such as thrombelastography (TEG) and rotational
      thrombelastometry (ROTEM), have emerged as point-of-care tools that can guide the
      hemostatic resuscitation of bleeding injured patients. This article describes the
      role of TEG in contemporary trauma care by explaining this assay's methodology,
      clinical applications, and result interpretation through description of
      supporting studies to provide the reader with an evidence-based user's guide.
      Although TEG and ROTEM are assays based on the same viscoelastic principle, this
      article is focused on data supporting the use of TEG in trauma, because it is
      available in trauma centers in North America; ROTEM is mostly available in
      Europe.

PMID- 27894495
TI  - Rib Fracture Fixation: Indications and Outcomes.
AB  - Rib fractures are a frequently identified injury in the trauma population. Not
      only are multiple rib fractures painful, but they are associated with an
      increased risk of adverse outcomes. Pneumonia in particular can be devastating,
      especially to an elderly patient, but other complications such as prolonged
      ventilation and increased intensive care and hospital durations of stay have a
      negative impact on the patient. Computed tomography scan is the best modality to
      diagnosis rib fractures but the treatment of fractures is still evolving.
      Currently patient care involves a multidisciplinary approach that includes pain
      control, aggressive pulmonary therapy, and possibly surgical fixation.

PMID- 27894497
TI  - Trauma Quality Improvement.
AB  - Trauma centers and a third-party payer within Michigan built a regional
      collaborative quality initiative. Hallmarks of the collaborative are standardized
      data collection, annual data validation visits, face-to-face collaborative
      meetings, and dedication to performance improvement. The Michigan Trauma Quality
      Improvement Program has shown measurable improvement in patient outcomes,
      resource use, and compliance with processes of care.

PMID- 27894498
TI  - Noncompressible Torso Hemorrhage.
AB  - Noncompressible torso hemorrhage (NCTH) constitutes a leading cause of
      potentially preventable trauma mortality. NCTH is defined by high-grade injury
      present in one or more of the following anatomic domains: pulmonary, solid
      abdominal organ, major vascular or pelvic trauma; plus hemodynamic instability or
      the need for immediate hemorrhage control. Rapid operative management, as part of
      a damage control resuscitation strategy, remains the mainstay of treatment.
      However, endovascular techniques are evolving and may become more mainstream with
      the advent of hybrid rooms that can deliver concurrent open and
      radiologic/endovascular management of traumatic hemorrhage.

PMID- 27894499
TI  - Resuscitative Endovascular Balloon Occlusion of the Aorta: Indications, Outcomes,
      and Training.
AB  - Exsanguinating torso hemorrhage is a leading killer of trauma patients. The most
      appropriate means of hemorrhage control must be used. Trauma surgeons should have
      expertise with all approaches for prompt hemorrhage control [laparotomy,
      thoracotomy, resuscitative endovascular balloon occlusion of the aorta (REBOA),
      and resuscitative thoracotomy]. REBOA is an exciting adjunct for hemorrhage
      control as it can be deployed quickly and placed percutaneously. Balloon
      inflation can vary dependent on patient physiology. REBOA is effective in
      hemorrhagic shock as a bridge to definitive hemostasis. Endovascular training is
      important for trauma surgeons caring for patients at high risk of death from
      traumatic hemorrhage.

PMID- 27894494
TI  - Optimal Fluid Therapy for Traumatic Hemorrhagic Shock.
AB  - The resuscitation of traumatic hemorrhagic shock has undergone a paradigm shift
      in the last 20 years with the advent of damage control resuscitation (DCR). Major
      principles of DCR include minimization of crystalloid, permissive hypotension,
      transfusion of a balanced ratio of blood products, and goal-directed correction
      of coagulopathy. In particular, plasma has replaced crystalloid as the primary
      means for volume expansion for traumatic hemorrhagic shock. Predicting which
      patient will require DCR by prompt and accurate activation of a massive
      transfusion protocol, however, remains a challenge.

PMID- 27894500
TI  - Prediction of Massive Transfusion in Trauma.
AB  - Hemorrhage is the leading cause of preventable death in trauma. Damage control
      resuscitation relies on permissive hypotension, minimizing crystalloid use, and
      early implementation of massive transfusion protocols with established blood
      component ratios. These protocols improve the survival of the severely injured
      patient. Trauma physicians must quickly and accurately predict when a massive
      transfusion protocol should be activated. Several validated transfusion scores
      have been developed for this purpose. Many of these scores are useful for
      resuscitation research. One option, the ABC score, is an accurate, validated, and
      clinically useful score that is simple to calculate and rapidly obtained.

PMID- 27894496
TI  - Postinjury Inflammation and Organ Dysfunction.
AB  - The development of organ dysfunction (OD) is related to the intensity and balance
      between trauma-induced simultaneous, opposite inflammatory responses. Early
      proinflammation via innate immune system activation may cause early OD, whereas
      antiinflammation, via inhibition of the adaptive immune system and apoptosis, may
      induce immunoparalysis, impaired healing, infections, and late OD. Patients
      discharged with low-level OD may develop the persistent inflammation
      immunosuppression catabolism syndrome. Although the incidence of multiple organ
      failure has decreased over time, it remains morbid, lethal, and resource
      intensive. However, single OD, especially acute lung injury, remains frequent.
      Treatment is limited, and prevention remains the mainstay strategy.

PMID- 27894501
TI  - Tranexamic Acid Update in Trauma.
AB  - Following results from the CRASH-2 trial, tranexamic acid (TXA) gained
      considerable interest for the treatment of hemorrhage in trauma patients.
      Although TXA is effective at reducing mortality in patients presenting within 3
      hours of injury, optimal dosing, timing of administration, mechanism, and
      pharmacokinetics require further elucidation. The concept of fibrinolysis
      shutdown in hemorrhagic trauma patients has prompted discussion of real-time
      viscoelastic testing and its potential role for appropriate patient selection.
      The results of ongoing clinical trials will help establish high-quality evidence
      for optimal incorporation of TXA in mature trauma networks in the United States
      and abroad.

PMID- 27894503
TI  - Editorial.

PMID- 27894502
TI  - Advances in Trauma-2016: Goal Zero Preventable Deaths After Injury.

PMID- 27894504
TI  - [Contribution and challenges of Big Data in oncology].
AB  - Since the first draft of the human genome sequence published in 2001, the cost of
      sequencing has dramatically decreased. The development of new technologies such
      as next generation sequencing led to a comprehensive characterization of a large
      number of tumors of various types as well as to significant advances in precision
      medicine. Despite the valuable information this technological revolution has
      allowed to produce, the vast amount of data generated resulted in the emergence
      of new challenges for the biomedical community, such as data storage, processing
      and mining. Here, we describe the contribution and challenges of Big Data in
      oncology.

PMID- 27894505
TI  - [Prostate cancer: To treat or not to treat?]

PMID- 27894506
TI  - A non-surgical treatment for inferior vena cava pseudoaneurysm post-hepatectomy.

PMID- 27894509
TI  - Reply.

PMID- 27894508
TI  - Intrapancreatic accessory spleen (IPAS): A single-institution experience and
      review of the literature.
AB  - INTRODUCTION: Accessory spleens located within the pancreatic parenchyma
      (intrapancreatic accessory spleen, IPAS) pose a unique clinical challenge. In
      many cases, despite imaging and other diagnostic studies, malignancy cannot be
      excluded and patients are subjected to pancreatic resection. We review our
      experience with the presentation, diagnosis, and treatment of patients with IPAS
      to provide insight into improving pre-operative evaluation of these patients
      METHODS: A retrospective chart review identified seven patients who underwent
      surgical resection of an intrapancreatic spleen at University of Louisville
      Hospital between 2004 and 2015. Charts were analyzed for presenting symptoms, pre
      operative imaging, operative therapy, and final pathologic evaluation. Patients
      were included in the study if they underwent pancreatic resection for a
      pancreatic mass and were diagnosed with an IPAS on final pathologic evaluation.
      RESULTS: Patient age ranged from 38 to 72 with a median age of 62.5, including
      five males and two females. Lesions ranged from 1.4 to 7.4 cm in maximal diameter
      (mean 3.8 cm). All lesions were identified as round, hypervascular, well
      circumscribed masses in the pancreatic tail. The most common pre-operative
      diagnosis was a non-functioning pancreatic neuroendocrine tumor (NF-PNET). The
      most common operative approach was laparoscopic distal pancreatectomy and
      splenectomy. CONCLUSION: IPAS are benign tumors commonly mistaken for pancreatic
      neoplasms such as NF-PNET. A combination of CT, MRI and nuclear medicine
      examinations can confirm the diagnosis of IPAS and prevent unnecessary surgical
      resection.

PMID- 27894507
TI  - Do simple beside lung function tests predict morbidity after rib fractures?
AB  - BACKGROUND: We evaluated if incentive spirometry volume (ISV) and peak expiratory
      flow rate (PEFR) could predict acute respiratory failure (ARF) in patients with
      rib fractures. METHODS: Normotensive, co-operative patients were enrolled
      prospectively. ISV and PEFR were measured on admission, at 24 h and at 48 h by
      taking the best of three readings each time. The primary outcome, ARF, was
      defined as requiring invasive or noninvasive positive pressure ventilation.
      RESULTS: 99 patients were enrolled (median age, 77 years). ARF occurred in 9%. Of
      the lung function tests, only a low median ISV at admission was associated with
      ARF (500 ml vs 1250 ml, p = 0.04). Three of 69 patients with ISV of >=1000 ml
      versus six of 30 with ISV <1000 ml developed ARF (p = 0.01). Other significant
      factors were: number of rib fractures, tube thoracostomy, any lower-third rib
      fracture, flail segment. CONCLUSION: PEFR did not predict ARF. Admission ISV may
      have value in predicting ARF.

PMID- 27894510
TI  - Real-World Outcomes of Ranibizumab Treatment for Diabetic Macular Edema in a
      United Kingdom National Health Service Setting.

PMID- 27894511
TI  - Increased Choroidal Vascularity in Central Serous Chorioretinopathy Quantified
      Using Swept-Source Optical Coherence Tomography.

PMID- 27894513
TI  - Complement in the fundamental processes of the cell.
AB  - Once regarded solely as an activator of innate immunity, it is now clear that the
      complement system acts in an assortment of cells and tissues, with immunity only
      one facet of a diverse array of functions under the influence of the complement
      proteins. Throughout development, complement activity has now been demonstrated
      from early sperm-egg interactions in fertilisation, to regulation of epiboly and
      organogenesis, and later in refinement of cerebral synapses. Complement has also
      been shown to regulate homeostasis of adult tissues, controlling cell processes
      such as migration, survival, repair, and regeneration. Given the continuing
      emergence of such novel actions of complement, the existing research likely
      represents only a fraction of the myriad of functions of this complex family of
      proteins. This review is focussed on outlining the current knowledge of
      complement family members in the regulation of cell processes in non-immune
      systems. It is hoped this will spur research directed towards revealing more
      about the role of complement in these fundamental cell processes.

PMID- 27894512
TI  - Probabilistic approach for assessing infants' health risks due to ingestion of
      nanoscale silver released from consumer products.
AB  - Silver nanoparticles (n-Ag) are widely used in consumer products and many medical
      applications because of their unique antibacterial properties. Their use is
      raising concern about potential human exposures and health effects. Therefore, it
      is informative to assess the potential human health risks of n-Ag in order to
      ensure that nanotechnology-based consumer products are deployed in a safe and
      sustainable way. Even though toxicity studies clearly show the potential hazard
      of n-Ag, there have been few attempts to integrate hazard and exposure
      assessments to evaluate risks. The underlying reason for this is the difficulty
      in characterizing exposure and the lack of toxicity studies essential for human
      health risk assessment (HHRA). Such data gaps introduce significant uncertainty
      into the risk assessment process. This study uses probabilistic methods to assess
      the relative uncertainty and potential risks of n-Ag exposure to infants. In this
      paper, we estimate the risks for infants potentially exposed to n-Ag through
      drinking juice or milk from sippy cups or licking baby blankets containing n-Ag.
      We explicitly evaluate uncertainty and variability contained in available dose
      response and exposure data in order to make the risk characterization process
      transparent. Our results showed that individual margin of exposures for oral
      exposure to sippy cups and baby blankets containing n-Ag exhibited minimal risk.

PMID- 27894514
TI  - Corrigendum to "Recurrence of suicide attempt in adolescents lost to contact
      early by clinicians: The 10-year REPEATERS cohort of French adolescents" [Journal
      of Adolescence 43 (2015) 111-118].

PMID- 27894515
TI  - Glycine buffered synthesis of layered iron(II)-iron(III) hydroxides (green
      rusts).
AB  - Layered FeII-FeIII hydroxides (green rusts, GRs) are efficient reducing agents
      against oxidizing contaminants such as chromate, nitrate, selenite, and
      nitroaromatic compounds and chlorinated solvents. In this study, we adopted a
      buffered precipitation approach where glycine (GLY) was used in the synthesis of
      sulfate-interlayered GR (GRSO4) by aerial oxidation of FeII or co-precipitation
      by adding FeIII salt to an aqueous solution of FeII at constant pH. In both the
      oxidation and the co-precipitation methods pure crystalline GRSO4 was
      precipitated in the presence of 70mM GLY (pH 8.0), whereas in the absence of GLY,
      synthesis failed under similar conditions. Gycine functions as both a pH buffer
      and a ligand; FeII-GLY complexes serve as a source of base (FeII-GLY+H2O->FeII+H
      GLY+OH-) during GR formation, supplying about 45% of the total base required for
      the synthesis. The GLY buffer decreases pH fluctuations during base addition and
      hence allows for fast GRSO4 precipitation, minimizing byproduct formation. The
      use of other pH buffers [4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid and 2
      amino-2-(hydroxymethyl)-1,3-propanediol] was also tested but failed. Mossbauer
      spectroscopy, X-ray diffraction, Fourier transform infrared, transmission
      electron microscopy, and FeII measurements confirmed the purity, stoichiometry,
      and pyroaurite-type structure of the obtained GRSO4. The formula of GRSO4 was
      found to be FeII4.08FeIII1.98(OH)11.6(SO4)1.00, and the tabular GR crystals had a
      lateral size of 100-500nm and a thickness of about 40nm. Upscaling of the
      synthesis by either 25 times in volume or 20 times in FeII concentration resulted
      in pure GRSO4 products. Compared with the conventional unbuffered GRSO4 synthesis
      method, the present method can provide pure products with a controllable, fast,
      and low-cost process.

PMID- 27894516
TI  - [Gallibacterium anatis pulmonary abscess].

PMID- 27894517
TI  - Bilateral choroidal effusion after selective laser trabeculoplasty.
AB  - Selective laser trabeculoplasty (SLT) is an effective treatment to treat open
      angle glaucoma with a low risk of complications. The case is presented of a 73
      year-old woman with uncontrolled primary open-angle glaucoma who underwent
      selective laser trabeculoplasty in both eyes and developed bilateral choroidal
      effusion.

PMID- 27894518
TI  - Radiation maculopathy treated with intravitreal bevacizumab.
AB  - CASE REPORT: A 47 year-old woman with a choroidal melanoma developed a macular
      oedema secondary to radiation therapy 75 months after brachytherapy plaque. The
      patient received 3 intravitreal Bevacizumab injections. DISCUSSION: The patient
      had a good response to bevacizumab treatment. In fact, there was a reduction in
      the macular oedema measured by optical coherence tomography (OCT) scan, as well
      as an improvement in best corrected visual acuity. There was no recurrence of
      macular oedema, and visual acuity remained stable after 3-years follow-up.

PMID- 27894519
TI  - Proptosis as initial manifestation of Burkitt's lymphoma with orbital
      involvement.
AB  - CASE PRESENTATION: A 35-year-old woman without any known systemic disorder
      presented with a complaint of painful and rapidly increasing proptosis in her
      right eye. Based on the clinical, radiological, analytical and ophthalmological
      assessments, the diagnosis made was Burkitt's lymphoma in acquired
      immunodeficiency syndrome. CONCLUSION: Proptosis can be an unusual way of
      presenting with Burkitt's lymphoma associated with acquired immunodeficiency.
      This differential diagnosis is important because confirmation leads to a change
      in the vital prognosis of the patient.

PMID- 27894520
TI  - Corrigendum to "All-ceramic or metal-ceramic tooth-supported fixed dental
      prostheses (FDPs)? A systematic review of the survival and complication rates.
      Part II: Multiple-unit FDPs" [Dental Materials 31 (6) (2015) 624-639].

PMID- 27894521
TI  - Effect of 3 cements on white spot lesion formation after full-coverage rapid
      maxillary expander: A comparative in-vivo study.
AB  - INTRODUCTION: The aim of this study was to assess the effects of 3 luting agents
      (glass ionomer cement, compomer, and polycarboxylate cement) on white spot lesion
      formation in patients with full-coverage bonded acrylic splint expanders. White
      spot lesion formation was assessed with quantitative light-induced fluorescence.
      METHODS: Full-coverage rapid maxillary expanders were cemented with glass ionomer
      cement, compomer, and polycarboxylate cement in groups 1, 2, and 3, respectively.
      A control group comprised patients who never had orthodontic treatment.
      Quantitative light-induced fluorescence images taken before and after rapid
      maxillary expansion treatment were analyzed for these parameters: the percentages
      of fluorescence loss with respect to the fluorescence of sound tooth tissue
      (DeltaF) and maximum loss of fluorescence intensity in the whole lesion; lesion
      area with DeltaF equal to less than a -5% threshold; and the percentage of
      fluorescence loss with respect to the fluorescence of sound tissue times the area
      that indicated lesion volume. RESULTS: All 3 groups showed statistically
      significantly greater demineralization than the control group. The 3 experimental
      groups differed from each other in half of the parameters calculated. Teeth in
      the polycarboxylate group developed the most white spot lesions. CONCLUSIONS:
      With the highest rate of white spot lesion formation, polycarboxylate cements
      should not be used for full-coverage bonded acrylic splint expanders. Compomers
      may be preferred over glass ionomer cements, based on the findings of this study.

PMID- 27894522
TI  - Nickel-free vs conventional braces for patients allergic to nickel: Gingival and
      blood parameters during and after treatment.
AB  - INTRODUCTION: Allergic and inflammatory reactions have commonly been associated
      with the release of metal ions during orthodontic treatment. Our objective was to
      evaluate prospectively gingival and blood status in patients allergic to nickel.
      METHODS: Allergy to nickel was diagnosed using a patch test. Two groups were
      established: conventional braces (n = 21) and nickel-free braces (n = 21). The
      gingival index was used to determine gingival status before treatment,
      periodically for 12 months (evaluations every 3 months), and 1 month after the
      removal of the braces. Blood status was evaluated with a complete blood count,
      including the quantification of nickel and immunoglobin E before treatment,
      during treatment, and 1 month after removal of the braces. The data were analyzed
      using Mann-Whitney, Student t, Wilcoxon, repeated measures analysis of variance,
      Friedman, and chi-square tests. Either the Pearson or the Spearman correlation
      coefficients were calculated, when appropriate. RESULTS: The number of basophils
      increased significantly among the evaluations in both groups (conventional, P =
      0.002; nickel-free, P = 0.001), whereas the number of eosinophils and the
      immunoglobin E levels decreased significantly in the conventional group (P =
      0.004). Plasma nickel levels were increased before and during treatment, and
      decreased 1 month after removing the braces in both groups, but the differences
      were significant only in the nickel-free group (P = 0.002). No correlations were
      found between the concentrations of nickel and immunoglobin E, basophils, or
      eosinophils, or between the gingival index and either bands or segmented
      neutrophils (P >= 0.05). CONCLUSIONS: Patients treated with nickel-free braces
      had better gingival health and smaller blood changes than did those treated with
      conventional braces. All abnormalities tended to be eliminated after the removal
      of the braces.

PMID- 27894523
TI  - Serum and urine insulin-like growth factor-1 as biochemical growth maturity
      indicators.
AB  - INTRODUCTION: Biochemical markers are agents directly involved in bone growth and
      remodeling and can be quantitatively evaluated from various biologic fluids. The
      aim of this study was to assess the changes in the levels of insulin-like growth
      factor-1 (IGF-1) in serum and urine as a growth maturity indicator and to compare
      them with the cervical vertebral maturation radiographic stages. METHODS: The
      study was conducted with 72 female subjects aged 8 to 20 years. Cervical
      vertebral maturation stages, and serum and urine IGF-1 levels were recorded for
      all subjects, and the subjects were equally divided into the 6 cervical vertebral
      maturation groups. Median values of IGF-1 for each stage of cervical vertebral
      maturation were calculated and statistically compared with those of the other
      stages. RESULTS: The levels of serum and urine IGF-1 at stage 4 of cervical
      vertebral maturation were significantly higher than those from the other stages
      (P <0.01). Stage 4 corresponded to a mean age of 13.67 years. A significant
      correlation was observed between serum and urine IGF-1 (P <0.001). CONCLUSIONS:
      Urine IGF-1 follows the growth curve similar to serum IGF-1. Thus, urine IGF-1
      may be regarded as a promising noninvasive tool for growth assessment. Further
      research is necessary to validate these results in a different population and
      with a larger sample.

PMID- 27894524
TI  - Defining the location of the dental midline is critical for oral esthetics in
      camouflage orthodontic treatment of facial asymmetry.
AB  - When considering camouflage orthodontic treatment of a malocclusion associated
      with significant facial asymmetry, it is important to define the location of the
      dental midline. The patient, a 19-year-old Japanese woman, had an anterior open
      bite and a dental midline discrepancy associated with facial asymmetry. A
      nonsurgical treatment plan was considered. The main treatment objective was to
      correct the anterior open bite and the dental midlines in both arches. The dental
      midline discrepancy was eliminated, and proper overjet and overbite were
      achieved. Although the facial asymmetry remained, oral esthetics dramatically
      improved and a favorable occlusion was obtained. The results suggest that
      appropriately defining the location of the dental midline is critical for
      successful camouflage treatment of facial asymmetry.

PMID- 27894525
TI  - Canine-lateral incisor transposition: Controlling root resorption with a bone
      anchored T-loop retraction.
AB  - A 12-year-old girl presented with a Class II Division 1 malocclusion, complicated
      by a complete transposition of the maxillary left canine into the position
      normally occupied by the left lateral incisor. Dental and medical histories were
      noncontributory. Brackets were bonded on all maxillary teeth, from first molar to
      first molar, except for the left lateral incisor. Because the lateral incisor was
      not engaged on the archwire, the tooth was free to physiologically move out of
      the path of canine root movement. To prepare the site for canine retraction, a
      coil spring was used to open space between the left central incisor and the first
      premolar. A 2 * 12-mm stainless steel miniscrew was placed in the infrazygomatic
      crest, labial to the mesiodistal cusp of the maxillary left first molar. A 0.019
      * 0.025-in titanium-molybdenum alloy T-loop, anchored by the miniscrew, was used
      to retract the canine root over the labial surface of the root of the distally
      positioned lateral incisor. In 24 months, this difficult malocclusion, with a
      Discrepancy Index score of 18, was treated to a Cast-Radiograph Evaluation score
      of 26.

PMID- 27894526
TI  - Simplifying optimal tooth-size calculations and communications between
      practitioners.
AB  - The purpose of this article is to present a simple method for determining the
      optimal sizes of anterior teeth. This is needed because of the frequency of
      anomalous and missing maxillary lateral incisors. In addition to anomalous and
      missing incisors, other factors that create challenges for the dentist and
      orthodontist when designing an esthetic and occlusally sound dentition are
      attrition, trauma, transposition, erosion, and caries. Optimal esthetics and
      occlusion require correctly sized teeth in proportion to themselves and the other
      teeth. Orthodontics, in partnership with restorative dentistry, allows doctors to
      accomplish the objectives of ideal occlusion and enhanced esthetics. Data
      compiled from previously published research enabled us to create simple formulae
      to determine optimal tooth sizes, an esthetic guide worksheet to use with
      collaborating dentists, and a sample written communication to accompany the
      completed esthetic guide worksheet. The method for establishing optimal tooth
      sizes is presented in a manner that allows easy memorization of the formulae and
      determination of the best dimensions for teeth without the use of a calculator.

PMID- 27894528
TI  - Stepstools and ladders.

PMID- 27894527
TI  - Accuracy and mechanical properties of orthodontic models printed 3-dimensionally
      from calcium sulfate before and after various postprinting treatments.
AB  - INTRODUCTION: Dental models fabricated with 3-dimensional printing technologies
      are revolutionizing the practice of orthodontics, but they generally comprise
      polymeric materials that may not be suitable for certain applications, such as
      soldering appliances. The objective of this study was to investigate the
      dimensional accuracy and mechanical properties of 3-dimensional printed ceramic
      based models before and after various treatments intended to improve their
      mechanical properties. METHODS: Thirty identical models were printed 3
      dimensionally from a calcium sulfate-based substrate and divided into 3 groups
      for treatment: high heat (250 degrees C for 30 minutes), low heat (150 degrees C
      for 30 minutes), and Epsom salt treatment. Each model was scanned before and
      after treatment with a laser scanner, and dimensional stability was analyzed by
      digital superimpositions using a best-fit algorithm. The models were weighed
      before and after treatment to evaluate mass changes. Additionally, 3-dimensional
      printed cylinders treated as described above and an untreated control group were
      subjected to compressive mechanical testing (n = 11 per group). RESULTS: The
      Epsom salt treatment group had statistically significant increases in both peak
      compressive stress and modulus of elasticity when compared with the other
      treatment groups. All treatment groups had statistically significant changes in
      mass, with the Epsom salt group gaining mass and the 2 heat-treatment groups
      losing mass. The low-temperature treatment group had a statistically
      significantly lower mean average for dimensional deviations (0.026 +/- 0.010 mm)
      than did the other treatment groups (0.069 +/- 0.006 and 0.059 +/- 0.010 mm for
      high temperature and Epsom salt, respectively). CONCLUSIONS: Dental models
      printed 3-dimensionally with calcium sulfate and treated with Epsom salt showed
      significant improvement in compressive mechanical properties and retained
      clinically acceptable dimensional stability.

PMID- 27894529
TI  - The chi-square test for trend.

PMID- 27894530
TI  - Reprise: Very rapid orthodontic treatment.

PMID- 27894531
TI  - Adenomatoid odontogenic tumor: An outdated report.

PMID- 27894532
TI  - Authors' response.

PMID- 27894533
TI  - Determining the midsagittal reference plane for evaluating facial asymmetries.

PMID- 27894534
TI  - Authors' response.

PMID- 27894535
TI  - Authors' response.

PMID- 27894536
TI  - Criteria for determining facial asymmetries.

PMID- 27894537
TI  - Correction.

PMID- 27894539
TI  - Beyond your comfort zone.

PMID- 27894540
TI  - Effect of supplemental vibrational force on orthodontically induced inflammatory
      root resorption: A multicenter randomized clinical trial.
AB  - INTRODUCTION: A multicenter parallel 3-arm randomized clinical trial was carried
      out in 1 university and 2 district hospitals in the United Kingdom to investigate
      the effect of supplemental vibrational force on orthodontically induced
      inflammatory root resorption (OIIRR) during the alignment phase of fixed
      appliance therapy. METHODS: Eighty-one subjects less than 20 years old with
      mandibular incisor irregularity undergoing extraction-based fixed-appliance
      treatment were randomly allocated to supplementary (20 minutes a day) use of an
      intraoral vibrational device (AcceleDent; OrthoAccel Technologies, Houston, Tex)
      (n = 29), an identical nonfunctional (sham) device (n = 25), or fixed appliances
      only (n = 27). OIIRR was measured blindly from long-cone periapical radiographs
      of the maxillary right central incisor taken at the start of treatment and the
      end of alignment when a 0.019 * 0.025-in stainless steel archwire was placed
      (mean follow-up, 201.6 days; 95% confidence interval [CI], 188.6-214.6 days).
      Data were analyzed blindly on a per-protocol basis because losses to follow-up
      were minimal, with descriptive statistics, 1-way analysis of variance, and
      univariable and multivariable regression modeling. RESULTS: Nine patients were
      excluded from the analysis; they were evenly distributed across the groups. Mean
      overall OIIRR measured among the 72 patients was 1.08 mm (95% CI, 0.89-1.27 mm).
      Multivariable regression indicated no significant difference in OIIRR for the
      AcceleDent (difference, 0.22 mm; 95% CI, -0.14-0.72; P = 0.184) and AcceleDent
      sham groups (difference, 0.29 mm; 95% CI, -0.15-0.99; P = 0.147) compared with
      the fixed-appliance-only group, after accounting for patient sex, age,
      malocclusion, extraction pattern, alignment time, maximum pain experienced,
      history of dentoalveolar trauma, and initial root length of the maxillary right
      central incisor. No other side-effects were recorded apart from pain and OIIRR.
      CONCLUSIONS: The use of supplemental vibrational force during the alignment phase
      of fixed appliance orthodontic treatment does not affect OIIRR associated with
      the maxillary central incisor. REGISTRATION: ClinicalTrials.gov (NCT02314975).
      PROTOCOL: The protocol was not published before trial commencement. FUNDING:
      Functional and sham AcceleDent units were donated by the manufacturer; there was
      no contribution to the conduct or the writing of this study.

PMID- 27894541
TI  - Assessment of the changes in arch perimeter and irregularity in the mandibular
      arch during initial alignment with the AcceleDent Aura appliance vs no appliance
      in adolescents: A single-blind randomized clinical trial.
AB  - INTRODUCTION: The purpose of this 2-arm parallel trial was to assess the effects
      of the AcceleDent Aura (OrthoAccel Technologies, Houston, Tex) appliance on the
      increase in mandibular anterior arch perimeter, the reduction in mandibular arch
      irregularity, and the amount of discomfort during initial alignment of the
      mandibular arch with fixed appliances. METHODS: Forty Class II adolescent
      patients with full fixed appliances and treated with maxillary premolar
      extractions and no extractions in the mandibular arch participated in this
      randomized clinical trial. They were recruited in a private practice and treated
      by 1 clinician. Randomization to either a no-appliance group or the AcceleDent
      Aura appliance group was accomplished with permuted blocks of 10 patients with
      the allocations concealed in opaque, sealed envelopes. Both the operator and the
      outcome assessor were blinded, but it was not feasible to blind the patients.
      Discomfort was recorded during the first week of treatment. Mandibular anterior
      arch perimeter and anterior irregularity were measured from plaster models taken
      at the start of treatment and after 5, 8, and 10 weeks. RESULTS: No patients were
      lost to follow-up, and no data were missing. There was no difference in anterior
      arch perimeter at the start of treatment (P = 0.85; median, 0.6 mm; 95%
      confidence interval [CI], -1.6, +1.8 mm) or at any other time point (5 weeks: P =
      0.84; median, -0.2 mm; 95% CI, -1.6, +1.2 mm; 8 weeks: P = 0.56; median, -0.3 mm;
      95% CI, -1.6, +0.7 mm; 10 weeks: P = 0.67; median, -0.1 mm; 95% CI, -1.5, +1.1
      mm). There was also no difference between groups for incisor irregularity (P =
      0.46; median, -0.5 mm; 95% CI, -2.2, +2.8 mm; P = 0.80; median, 0.0 mm; 95% CI, 
      1.0, +1.1 mm; P = 0.70; median, 0.1 mm; 95% CI, -0.7, +0.8 mm; P = 0.65; median,
      0.2 mm; 95% CI, -0.6, +0.6 mm). No difference was detected at any time during the
      first week for discomfort (baseline: P = 0.84; median, -1.5 mm; 95% CI, -15.9,
      +9.8 mm; 6 hours: P = 0.96; median, 0.3 mm; 95% CI, -23.5, +21.8 mm; 1 day: P,
      0.75; median, -3.5 mm; 95% CI, -27.1, +26.9 mm; 3 days: P = 0.98; median, -0.6
      mm; 95% CI, -20.6, +20.0; 7 days: P = 0.57; median, 0.5 mm; 95% CI, -5.0, +5.3
      mm). However, significantly fewer participants in the AcceleDent Aura group used
      analgesics at day 1 (P = <0.01). CONCLUSIONS: The AcceleDent Aura appliance had
      no effect compared with no appliance on increasing anterior arch perimeter, or
      reducing irregularity or perceived discomfort during initial alignment with fixed
      appliances, although more subjects used painkillers at 24 hours in the no
      appliance group. REGISTRATION: This trial was not registered. PROTOCOL: The
      protocol was not published before trial commencement. FUNDING: A special research
      grant was obtained from the Australian Society of Orthodontists Foundation for
      Research and Education to purchase the AcceleDent Aura appliances and fund the
      statistical analysis.

PMID- 27894543
TI  - Relationship between head posture and the severity of obstructive sleep apnea.
AB  - INTRODUCTION: The objective of this study was to compare the head posture of
      patients with obstructive sleep apnea (OSA) having different levels of severity
      with that of control subjects. METHODS: One hundred subjects participated in this
      study. Seventy-five subjects underwent overnight polysomnography in a sleep
      laboratory and were allocated into "mild," "moderate," or "severe" OSA groups,
      and 25 subjects with no complaints regarding OSA were allocated into 1 group and
      served as the controls. Cephalometric radiographs were obtained from all
      participants in natural head position. Craniocervical, craniovertical, and
      cervicovertical angles were measured in the groups. Data were analyzed using the
      least significant difference. RESULTS: The results showed significant differences
      between the OSA groups and the control group, and among the test groups, in all
      craniocervical, craniovertical, and cervicovertical angles (P <0.05), except for
      1 craniovertical measurement (P >0.05). There were no significant differences in
      this measurement among the test groups and in any measurement between the mild
      and moderate OSA groups (P >0.05). CONCLUSIONS: Head posture showed significant
      differences in patients with OSA. In general, the more severe the OSA, the more
      extended the natural head position as indicated by increases in the
      craniocervical angles. The cervical posture parameters may indicate existing OSA.

PMID- 27894542
TI  - Effect of orthodontic treatment on the upper airway volume in adults.
AB  - INTRODUCTION: The aim of this study was to examine the effects of orthodontic
      treatment with and without extractions on the anatomic characteristics of the
      upper airway in adults. METHODS: For this retrospective study, the pretreatment
      and posttreatment cone-beam computed tomography scans of 74 adult patients
      meeting defined eligibility criteria were analyzed. Imaging software was used to
      segment and measure upper airway regions including the nasopharynx, the
      retropalatal, and retroglossal areas of the oropharynx, as well as the total
      airway. The Wilcoxon signed rank test was used to compare volumetric and minimal
      cross-sectional area changes from pretreatment to posttreatment. RESULTS: The
      reliability values were high for all measurements, with intraclass correlation
      coefficients of 0.82 or greater. The volumetric treatment changes for the
      extraction and nonextraction groups were as follows: total airway, 1039.6 +/-
      3674.3 mm3 vs 1719.2 +/- 4979.2 mm3; nasopharynx, 136.1 +/- 1379.3 mm3 vs -36.5
      +/- 1139.8 mm3; retropalatal, 412.7 +/- 3042.5 mm3 vs 399.3 +/- 3294.6 mm3; and
      retroglossal, 412.5 +/- 1503.2 mm3 vs 1109.3 +/- 2328.6 mm3. The treatment
      changes in volume or minimal cross-sectional area for all airway regions examined
      were not significantly (P >0.05) different between the extraction and
      nonextraction groups. CONCLUSIONS: Orthodontic treatment in adults does not cause
      clinically significant changes to the volume or the minimally constricted area of
      the upper airway. These results suggest that dental extractions in conjunction
      with orthodontic treatment have a negligible effect on the upper airway in
      adults.

PMID- 27894544
TI  - Effect of longitudinal flutes on miniscrew implant stability and 3-dimensional
      bone formation.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effects of
      longitudinal flutes on miniscrew implant (MSI) stability and bone healing.
      METHODS: Using 11 skeletally mature New Zealand white rabbits, we placed 31
      longitudinally fluted and 31 nonfluted, 3-mm-long MSIs in standardized positions
      in their calvaria and immediately loaded them with 100 g using nickel-titanium
      coil springs. Insertion torque values were obtained for each MSI placed; removal
      torque values were obtained for 28 MSIs that had been in place for 6 weeks and 20
      MSIs that had been in place for 2 weeks. The bone volume fractions at 6 to 24, 24
      to 42, and 42 to 60 MUm from the MSI surfaces were evaluated using microcomputed
      tomography with an isotropic resolution of 6 MUm. RESULTS: The success rate was
      97% for both the fluted and nonfluted MSIs. The difference in insertion torque
      between the fluted and nonfluted MSIs was not statistically significant (P =
      0.930). After 2 weeks, there was no statistically significant (P = 0.702)
      difference in removal torque between the fluted and nonfluted MSIs. After 6
      weeks, removal torque values were significantly (P = 0.008) higher for the fluted
      (3.42 +/- 0.26 N.cm) than the nonfluted (2.49 +/- 0.20 N.cm) MSIs. Bone volume
      fractions of the 6-to-24-, 24-to-42-, and 42-to-60-MUm layers were significantly
      (P <0.05) greater for the nonfluted than the fluted MSIs. CONCLUSIONS: Loaded 3
      mm-long MSIs with and without flutes have high success rates. Longitudinal flutes
      placed in 3-mm MSIs increased their removal torque by 37% and decreased the
      amount of bone immediately surrounding them.

PMID- 27894546
TI  - Innovative design of closing loops producing an optimal force system applicable
      in the 0.022-in bracket slot system.
AB  - INTRODUCTION: Most closing loops designed for producing higher moment-to-force
      (M/F) ratios require complex wire bending and are likely to cause hygiene
      problems and discomfort because of their complicated configurations. We aimed to
      develop a simple loop design that can produce optimal force and M/F ratio.
      METHODS: A loop design that can generate a high M/F ratio and the ideal force
      level was investigated by varying the portion and length of the cross-sectional
      reduction of a teardrop loop and the loop position. The forces and moments acting
      on closing loops were calculated using structural analysis based on the tangent
      stiffness method. RESULTS: An M/F ratio of 9.3 (high enough to achieve controlled
      movement of the anterior teeth) and an optimal force level of approximately 250 g
      of force can be generated by activation of a 10-mm-high teardrop loop whose cross
      section of 0.019 * 0.025 or 0.021 * 0.025 in was reduced in thickness by 50% for
      a distance of 3 mm from the apex, located between a quarter and a third of the
      interbracket distance from the canine bracket. CONCLUSIONS: The simple loop
      design that we developed delivers an optimal force and an M/F ratio for the
      retraction of anterior teeth, and is applicable in a 0.022-in slot system.

PMID- 27894545
TI  - Ability of mini-implant-facilitated micro-osteoperforations to accelerate tooth
      movement in rats.
AB  - INTRODUCTION: Although current techniques for accelerated tooth movement often
      involve invasive surgical procedures, micro-osteoperforations (MOPs) using mini
      implants may facilitate orthodontic tooth movement without raising flaps, reduce
      surgical risks, and increase patient acceptance. In this study, we evaluated the
      effectiveness of mini-implant-facilitated MOPs in inducing accelerated tooth
      movement and investigated the potential risks for root resorption. METHODS: Five
      MOPs were placed on the left side around the maxillary first molars in 6 rats
      using an automated mini-implant driver, whereas the right side received no MOPs
      as the control. Closed-coiled springs were secured from incisors to first molars
      for orthodontic tooth movement. Tooth movement was measured, and samples
      underwent radiologic and histologic analyses. RESULTS: The MOP side exhibited a
      1.86-fold increase in the rate of tooth movement with decreased bone density and
      bone volume around the first molars compared with the control side. Hematoxylin
      and eosin and tartrate-resistant acid phosphatase analyses showed increased
      numbers of osteoclasts as well as new bone formation. Three-dimensional
      volumetric analysis of all 5 roots of the maxillary first molars demonstrated no
      statistically significant difference in root volumes. CONCLUSIONS: Mini-implant
      facilitated MOPs accelerated tooth movement without increased risk for root
      resorption and therefore may become a readily available and efficient treatment
      option to shorten orthodontic treatment time with improved patient acceptance.

PMID- 27894547
TI  - Comparison of AdvanSync and intermaxillary elastics in the correction of Class II
      malocclusions: A retrospective clinical study.
AB  - INTRODUCTION: Our objectives were to compare the skeletal, dentoalveolar, and
      soft tissue effects of the AdvanSync appliance (Ormco, Glendora, Calif) with
      intermaxillary elastics in the correction of Class II malocclusions in growing
      patients. METHODS: A retrospective study was conducted using lateral cephalograms
      of patients taken before and after comprehensive orthodontic treatment; 41
      patients consecutively treated with the AdvanSync were compared with 41 similar
      patients treated with intermaxillary Class II elastics. All patients had
      significant growth potential during treatment, as assessed by cervical vertebral
      maturation. A comparison group was generated from historical data bases and
      matched to the experimental groups for skeletal age, sex, and craniofacial
      morphology. Treatment changes were evaluated between the time points using a
      custom cephalometric analysis generating 31 variables as well as regional
      superimpositions. Data were analyzed using 1-way analysis of variance and Tukey
      Kramer tests. RESULTS: The effects of the AdvanSync and fixed orthodontics
      included maxillary growth restriction, protrusion, proclination, and intrusion of
      the mandibular incisors as well as mesialization of the mandibular molars (P
      <0.01). The effects of Class II elastics and fixed orthodontics were similar to
      AdvanSync, with the exceptions of less maxillary growth restriction and greater
      retrusion and retroclination of the maxillary incisors (P <0.01). Significant
      mandibular growth stimulation, relative to the untreated controls, did not occur
      with either modality. CONCLUSION: AdvanSync and intermaxillary elastics were
      effective in normalizing Class II malocclusions during comprehensive fixed
      orthodontics. AdvanSync produced its effects through maxillary skeletal growth
      restriction and mandibular dentoalveolar changes. Class II elastics worked
      primarily through dentoalveolar changes in both the maxilla and the mandible.

PMID- 27894548
TI  - Effects of zygoma-gear appliance for unilateral maxillary molar distalization: A
      prospective clinical study.
AB  - INTRODUCTION: The aim of the study was to evaluate the dentoskeletal effects of
      the zygoma-gear appliance used for unilateral maxillary molar distalization in
      patients with Class II subdivision malocclusion. METHODS: This prospective
      clinical study consisted of 21 patients (9 boys, 12 girls; mean age, 15.68 +/-
      2.18 years) with unilateral Class II malocclusion treated using the unilateral
      zygoma-gear appliance supported by a zygomatic miniplate inserted on the Class II
      malocclusion side. The dentoskeletal effects of the system were evaluated using
      cephalometric lateral and panoramic films with a paired t test. RESULTS: The mean
      amount of distalization for the maxillary first molar was found to be 5.31 +/-
      2.46 mm (P <0.001) in 0.45 +/- 0.12 years, showing an amount of 0.98 mm of
      distalization per month. It was also accompanied by a slight intrusion (0.76 +/-
      2.85 mm; P >0.05) and distal tipping (6.39 degrees  +/- 5.39 degrees ; P <0.001)
      of the maxillary molars. The maxillary premolar also spontaneously moved distally
      1.63 +/- 1.90 mm (P <0.01) with distal tipping (4.05 degrees  +/- 3.47 degrees ;
      P <0.001). Moreover, the inclination of the maxillary incisors and overjet were
      decreased (-1.59 degrees  +/- 1.45 degrees , P <0.001; and -0.29 +/- 0.63 mm, P
      <0.05; respectively) showing no anchorage loss. No statistically significant
      changes were found for the skeletal and soft tissue measurements (P >0.05).
      CONCLUSIONS: The zygoma-gear appliance system is an effective method for
      unilateral maxillary molar distalization.

PMID- 27894549
TI  - Quantitative assessment of the effectiveness of phase 1 orthodontic treatment
      using the American Board of Orthodontics Discrepancy Index.
AB  - INTRODUCTION: This retrospective study included a sample of 300 randomly selected
      patients from the archived records of Saint Louis University's graduate
      orthodontic clinic, St. Louis, Mo, from 1990 to 2012. The objective of this study
      was to quantify the changes obtained in phase 1 of orthodontic treatment and
      determine how much improvement, if any, has occurred before the initiation of the
      second phase. METHODS: For the purpose of this study, prephase 1 and prephase 2
      records of 300 subjects were gathered. All were measured using the American Board
      of Ortodontics Discrepancy Index (DI), and a score was given for each phase. The
      difference of the 2 scores indicated the quantitative change of the complexity of
      the treatment. Paired t tests were used to compare the scores. Additionally, the
      sample was categorized into 3 groups according to the Angle classifications, and
      the same statistics were used to identify significant changes between the 2
      scores. Analysis of variance was applied to compare the 3 groups and determine
      which had the most change. Percentages of change were calculated for the
      significant scores. RESULTS: The total DI score overall and the scores of all 3
      groups were significantly reduced from before to after phase 1. Overall, 42%
      improvement was observed. The Class I group showed 49.3% improvement, the Class
      II group 34.5% and the Class III group 58.5%. Most components of the DI improved
      significantly, but a few showed negative changes. CONCLUSIONS: Significant
      reductions of DI scores were observed in the total sample and in all Angle
      classification groups. This indicates that early treatment reduces the complexity
      of the malocclusions. Only 2 components of the DI showed statistically
      significant negative changes.

PMID- 27894551
TI  - A 47-Year-Old Man With a Spinal Cord Injury After a Parachute Jump.

PMID- 27894552
TI  - Hemodynamic Monitoring: Part 2.

PMID- 27894553
TI  - Drones Rule!

PMID- 27894556
TI  - Benchmarking Pain Assessment Rate in Critical Care Transport.
AB  - The purpose of this study is to determine the rate of pain assessment in
      pediatric neonatal critical care transport (PNCCT). The GAMUT database was
      interrogated for an 18-month period and excluded programs with less than 10%
      pediatric or neonatal patient contacts and less than 3 months of any metric data
      reporting during the study period. We hypothesized pain assessment during PNCCT
      is superior to prehospital pain assessment rates, although inferior to in
      hospital rates. Sixty-two programs representing 104,445 patient contacts were
      analyzed. A total of 21,693 (20.8%) patients were reported to have a documented
      pain assessment. Subanalysis identified 17 of the 62 programs consistently
      reporting pain assessments. This group accounted for 24,599 patients and included
      7,273 (29.6%) neonatal, 12,655 (51.5%) pediatric, and 4,664 (19.0%) adult
      patients. Among these programs, the benchmark rate of pain assessment was 90.0%.
      Our analysis shows a rate below emergency medical services and consistent with
      published hospital rates of pain assessment. Poor rates of tracking of this
      metric among participating programs was noted, suggesting an opportunity to
      investigate the barriers to documentation and reporting of pain assessments in
      PNCCT and a potential quality improvement initiative.

PMID- 27894557
TI  - Reporting Helicopter Emergency Medical Services in Major Incidents: A Delphi
      Study.
AB  - OBJECTIVE: Research on helicopter emergency medical services (HEMS) in major
      incidents is predominately based on case descriptions reported in a heterogeneous
      fashion. Uniform data reported with a consensus-based template could facilitate
      the collection, analysis, and exchange of experiences. This type of database
      presently exists for major incident reporting at www.majorincidentreporting.net.
      This study aimed to develop a HEMS-specific major incident template. METHODS:
      This Delphi study included 17 prehospital critical care physicians with current
      or previous HEMS experience. All participants interacted through e-mail. We asked
      these experts to define data variables and rank which were most important to
      report during an immediate prehospital medical response to a major incident. Five
      rounds were conducted. RESULTS: In the first round, the experts suggested 98
      variables. After 5 rounds, 21 variables were determined by consensus. These
      variables were formatted in a template with 4 main categories: HEMS background
      information, the major incident characteristics relevant to HEMS, the HEMS
      response to the major incident, and the key lessons learned. CONCLUSION: Based on
      opinions from European experts, we established a consensus-based template for
      reporting on HEMS responses to major incidents. This template will facilitate
      uniformity in the collection, analysis, and exchange of experience.

PMID- 27894558
TI  - Helicopter Scene Response for Stroke Patients: A 5-Year Experience.
AB  - OBJECTIVE: The purpose of this study was to examine the usefulness of an
      emergency medical service (EMS)-requested air medical helicopter response
      directly to the scene for a patient with clinical evidence of an ischemic
      cerebrovascular accident (CVA) and transport to a regional comprehensive CVA
      center. METHODS: CareFlight, an air medical critical care transportation service,
      is based in Dayton, OH. The 3 CareFlight helicopters are geographically located
      and provided transport to all CVA scene patients in this study. A retrospective
      chart review was completed for all CareFlight CVA scene flights for 5 years (2011
      2015). A total of 136 adult patients were transported. EMS criteria included CVA
      symptom presence for less than 3 hours or awoke abnormal, nonhypoglycemia, and a
      significantly positive Cincinnati Prehospital Stroke Scale. RESULTS: The majority
      of patients (75%) met all 3 EMS CVA scene criteria; 27.5% of these patients
      received peripheral tissue plasminogen activator, and 9.8% underwent a
      neurointerventional procedure. CONCLUSION: Using a 3-step EMS triage for acute
      CVA, air medical transport from the scene to a comprehensive stroke center
      allowed for the timely administration of tissue plasminogen activator and/or a
      neurointerventional procedure in a substantive percentage of patients. Further
      investigation into air medical scene response for acute stroke is warranted.

PMID- 27894559
TI  - Helicopter Transport in Regionalized Burn Care: One Program's Perspective.
AB  - BACKGROUND: The decision to use helicopter EMS (HEMS) for the transport of burn
      patients is a complex decision. This analysis sought to evaluate burn patients
      flown to burn centers who met predetermined criteria for patients who likely
      benefit from HEMS care. METHODS: A retrospective transport chart review of all
      burn transports covering the preceding nine and a half years was conducted to
      evaluate for HEMS appropriate criteria defined as patients requiring advanced
      airway management, ventilator support, facial burns, inhalation injury,
      circumferential burns, electrical or chemical burn, or major burns. All ages were
      included. RESULTS: A total of 171 cases were identified. Thirty-one (18.1%) were
      pediatric. Facial burns constituted the most frequent criteria met with 112
      (65.5%) patients identified. Sixty-nine (40.4%) had suspected inhalation
      injuries. Fifty-five (32.2%) patients were intubated. Forty (28.6%) adults and
      twelve (38.7%) children had major burns. CONCLUSION: Of the 171 burn patient
      transported, twenty-one (12.3%) patients did not meet any HEMS criteria.
      Excluding those who did not meet any criteria, 98 (57.3%) patients were flown
      with non-major burns. Efforts are needed to determine the risks burn patients
      face if slower, non-critical care transport is utilized and which patients are
      appropriate for HEMS.

PMID- 27894560
TI  - Analysis of Temperature Variability in Medication Storage Compartments in
      Emergency Transport Helicopters.
AB  - The purpose of this study was to determine whether the temperature in medication
      storage compartments in air medical helicopters was within United States
      Pharmacopeia (USP)-defined limits for controlled room temperature. This was a
      prospective study using data obtained from a continuous temperature monitoring
      device. A total of 4 monitors were placed within 2 medication storage locations
      in 2 identical helicopters. The data collection period lasted 2 weeks during the
      summer and winter seasons. Data retrieved from monitors were compared against USP
      parameters for proper medication storage. Results documented temperatures outside
      the acceptable range a majority of the time with temperatures above the high
      limit during summer and below the low limit during winter. The study determined
      that compartments used for medication storage frequently fell outside of the
      range for USP-defined limits for medication storage. Flight programs should
      monitor storage areas, carefully taking actions to keep medication within defined
      ranges.

PMID- 27894561
TI  - Apneic Oxygenation May Not Prevent Severe Hypoxemia During Rapid Sequence
      Intubation: A Retrospective Helicopter Emergency Medical Service Study.
AB  - OBJECTIVE: This study sought to determine the effectiveness of apneic oxygenation
      in preventing hypoxemia during prehospital rapid sequence intubation (RSI).
      METHODS: We performed a case-cohort study using a pre-existing database looking
      at intubation management by a single helicopter emergency medical service between
      July 2013 and June 2015. Apneic oxygenation using high-flow nasal cannula (15
      L/min) was introduced to the standard RSI protocol in July 2014. Severe hypoxemia
      was defined as an incidence of oxygen saturation less than 90%. We compared
      patients who received apneic oxygenation during RSI with patients who did not
      using the Fisher exact test. RESULTS: Ninety-three patients were identified from
      the database; 29 (31.2%) received apneic oxygenation. Nineteen patients had an
      incidence of severe hypoxemia during RSI (20.43%; 95% confidence interval, 12.77%
      30.05%). There was no statistically significant difference between the rate of
      severe hypoxemia between patients in the apneic oxygenation group versus the
      control group (17.2% vs. 21.9%, P = .78). CONCLUSION: In this study, patients who
      received apneic oxygenation did not show a statistically significant difference
      in severe hypoxemia during RSI.

PMID- 27894562
TI  - Todd's Paresis in Acute Mild Head Trauma.
AB  - We present the case of an adult male who sustained Todd's paresis after a
      traumatically induced seizure in a patient with an isolated facial injury. The
      precipitating event was head trauma from a golf club. The patient had no previous
      history of seizures and went on to make a complete neurologic recovery with no
      cerebral pathology noted. A literature review suggests that Todd's paresis after
      trauma is very rare as opposed to occurring in the medical or long-term brain
      injury settings. Although the authors acknowledge that it may occur in trauma,
      the awareness within the prehospital setting is sufficiently rare for this case
      report to be of interest to prehospital clinicians; it is important prehospital
      clinicians are aware of this condition.

PMID- 27894563
TI  - Administration of CroFab Antivenom by a Helicopter Emergency Medical Service
      Team.
AB  - The case presented here highlights an unconventional use of a helicopter
      emergency medical service (HEMS) to provide a specialized medication to a
      critically ill patient when definitive transport was delayed. A 39-year-old man
      presented to a rural hospital 1 hour after sustaining a copperhead envenomation.
      He developed severe symptoms and was intubated. Arrangements were made for
      transfer to a tertiary referral center by HEMS, but because of incoming weather
      conditions, the team would not be able to make the return flight safely. The
      decision was made for the HEMS team to fly antivenom to the patient, administer
      the medication, and then transport the patient by ground to the tertiary medical
      center. This plan was executed, and the patient was safely transported to the
      accepting facility. Antivenom is most effective when administered early because
      this will halt the progression of edema and may reverse the systemic effects of
      envenomation. In this case, HEMS transport of antivenom to the patient with
      severe toxicity prevented a delay to administration and likely improved the
      patient's outcome. Although the traditional role of HEMS is to provide rapid
      transport to critically ill patients, HEMS teams can also function to deliver
      specialized medications to remote settings.

PMID- 27894564
TI  - Concern Network.

PMID- 27894565
TI  - Validating a summary measure of weight history for modeling the health
      consequences of obesity.
AB  - PURPOSE: Data on weight history may enhance the predictive validity of
      epidemiologic models of the health risks of obesity, but collecting such data is
      often not feasible. In this study, we investigate the validity of a summary
      measure of weight history. METHODS: We evaluated the quality of reporting of
      maximum weight in a sample of adults aged 50-84 years using data from the Health
      and Retirement Study. Recalled max body mass index (BMI, measured in kilogram per
      square meter) based on recalled weight in 2004 was compared with calculated max
      BMI based on self-reported weight collected biennially between 1992 and 2004.
      Logistic regression was used to assess similarity between the measures in
      predicting prevalent conditions. RESULTS: The correlation coefficient between
      recalled and calculated max weight in the overall sample was 0.95. Recalled max
      BMI value was within three BMI units of the calculated value 91.4% of the time.
      The proportions of individuals with obese I (BMI: 30.0-34.9), obese II (BMI: 35.0
      39.9), and obese III (BMI: 40.0 and above) were 28.8%, 12.7%, and 6.6% using
      recalled values compared with 27.1%, 10.5%, and 4.9% using calculated values. In
      multivariate analyses, the two BMI measures similarly predicted disease
      prevalence across a number of chronic conditions. CONCLUSIONS: Recalled max BMI
      was strongly correlated with max BMI calculated over the 12-year period before
      recall, suggesting that this measure can serve as a reliable summary measure of
      recent weight status.

PMID- 27894566
TI  - The association between handheld phone bans and the prevalence of handheld phone
      conversations among young drivers in the United States.
AB  - PURPOSE: Fourteen US states and the District of Columbia have banned handheld
      phone use for all drivers. We examined whether such legislation was associated
      with reduced handheld phone conversations among drivers aged younger than 25
      years. METHODS: Data from the 2008 to 2013 National Occupant Protection Use
      Survey were merged with states' legislation. The outcome was roadside-observed
      handheld phone conversation at stop signs or lights. Logistic regression was
      used. RESULTS: A total of 32,784 young drivers were observed. Relative to drivers
      who were observed in states without a universal handheld phone ban, the adjusted
      odds ratio of phone conversation was 0.42 (95% confidence interval, 0.33-0.53)
      for drivers who were observed in states with bans. The relative reduction in
      phone conversation was 46% (23%, 61%) for laws that were effective less than 1
      year, 55% (32%, 70%) for 1-2 years, 63% (51%, 72%) for 2 years or more, relative
      to no laws. CONCLUSIONS: Universal handheld phone bans may be effective at
      reducing handheld phone use among young drivers.

PMID- 27894568
TI  - Gender differences in cumulative life-course socioeconomic position and social
      mobility in relation to new onset diabetes in adults-the Brazilian Longitudinal
      Study of Adult Health (ELSA-Brasil).
AB  - PURPOSE: We investigated gender-specific associations of cumulative socioeconomic
      position across life course and social mobility with new onset diabetes mellitus
      (NODM) in over 12,000 civil servants in Brazil. METHODS: We used data from ELSA
      Brasil baseline (2008-2010). The accumulation of risk was assessed using an
      education-based score and an occupation-based score. Educational and occupational
      social mobility were also evaluated. RESULTS: In minimally adjusted models, NODM
      increased with increasing exposure to life-course social disadvantages,
      especially in men. This gender difference was pronounced when cumulative
      processes were evaluated by education-based scores (high vs. low cumulative
      social disadvantage, odds ratio [OR] = 4.7; 95% confidence interval [CI]: 2.6-8.5
      in men and OR = 2.0; 95% CI: 1.1-3.6 in women). After including proximal diabetes
      risk factors possibly acting as mediators, these associations remained high only
      in men (high vs. low cumulative social disadvantage, OR = 4.4; 95% CI: 2.4-8.1).
      Social mobility was associated with NODM in men. Compared to the high-stable
      trajectory, downward had greater associations than upward mobility. In women,
      when considering metabolic syndrome-related variables, changes in social
      hierarchy did not seem to have an influence on their risk of diabetes.
      CONCLUSIONS: Accumulation of risk and social mobility were associated with NODM
      with gender-specific patterns, suggesting differences in mechanisms connecting
      life-course socioeconomic position and diabetes in men and women.

PMID- 27894567
TI  - Proportion of selected congenital heart defects attributable to recognized risk
      factors.
AB  - PURPOSE: To assess the contribution of multiple risk factors for two congenital
      heart defects-hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot
      (TOF). METHODS: We used data from the National Birth Defects Prevention Study
      (1997-2011) to estimate average adjusted population attributable fractions for
      several recognized risk factors, including maternal prepregnancy overweight
      obesity, pregestational diabetes, age, and infant sex. RESULTS: There were 594
      cases of isolated simple HLHS, 971 cases of isolated simple TOF, and 11,829
      controls in the analysis. Overall, 57.0% of HLHS cases and 37.0% of TOF cases
      were estimated to be attributable to risk factors included in our model. Among
      modifiable HLHS risk factors, maternal prepregnancy overweight-obesity accounted
      for the largest proportion of cases (6.5%). Among modifiable TOF risk factors,
      maternal prepregnancy overweight-obesity and maternal age of 35 years or older
      accounted for the largest proportions of cases (8.3% and 4.3%, respectively).
      CONCLUSIONS: Approximately half of HLHS cases and one-third of TOF cases were
      estimated to be attributable to risk factors included in our models.
      Interventions targeting factors that can be modified may help reduce the risk of
      HLHS and TOF development. Additional research into the etiology of HLHS and TOF
      may reveal other modifiable risk factors that might contribute to primary
      prevention efforts.

PMID- 27894569
TI  - Five-Year Outcomes After Paclitaxel-Coated Balloon Angioplasty for Drug-Eluting
      Stent Restenosis.
AB  - The long-term outcomes of patients who underwent paclitaxel-coated balloon (PCB)
      angioplasty for drug-eluting stent restenosis (DES-ISR) remain unclear. We
      investigated the 5-year safety and efficacy outcomes of PCB angioplasty for DES
      ISR. The study included 185 patients with 216 DES-ISR lesions who underwent PCB
      angioplasty from September 2008 to December 2010. Two serial angiographic follow
      ups were routinely scheduled at 6 and 18 months after the index procedure. Five
      year clinical outcomes were investigated. The mean duration of follow-up was
      2,052 +/- 352.5 days, and 94.1% of the patients completed the 5-year follow-up.
      Recurrent restenosis was observed in 48 lesions (22.2%) at the 6-month follow-up
      and late restenosis was observed in 22 lesions (14.3%) at the 18-month follow-up.
      Very late restenosis was observed in 6 lesions (6.8%), and target lesion
      revascularization (TLR) was performed for 8 lesions (13.6%) beyond 24 months
      after the procedure. The cumulative rates of TLR at 1, 2, and 5 years were 16.4%,
      28.9%, and 34.1%, respectively. In patients who underwent TLR, 87% (52 of 60
      patients) underwent TLR within the first 2 years after the index procedure.
      Multivariable analysis revealed that in-stent occlusion lesion (odds ratio [OR]
      2.21; 95% confidence interval [CI] 1.09 to 4.47; p = 0.03), postprocedural
      percent diameter stenosis >35% (OR 3.19; 95% CI 1.54 to 6.68; p = 0.001), and
      right coronary artery ostial lesions (OR 5.56; 95% CI 1.40 to 24.9; p = 0.01)
      were independent predictors of recurrent restenosis. In conclusion, our results
      suggest that long-term outcomes after PCB angioplasty are acceptable; however,
      close follow-up during the first 2 years following this procedure may be
      necessary.

PMID- 27894570
TI  - An Overview of Pre-expanded Perforator Flaps: Part 1, Current Concepts.
AB  - Pre-expanded perforator flaps, a combination of tissue expansion with perforator
      flaps, are emerging as another landmark of plastic surgery. This flap inherits
      the characteristics of both perforator flaps and expanded flaps, making it a
      highly versatile option in reconstructive surgery. However, the definition of the
      pre-expanded perforator flap and the impact of pre-expansion on the superficial
      angio-architecture remain controversial. In this article, the authors review
      current concepts including the mechanism of expansion and the resultant changes
      in the angio-architecture. The authors also review the previous studies and
      classifications of pre-expanded perforator flaps.

PMID- 27894571
TI  - Pre-expanded Deep Inferior Epigastric Perforator Flap.
AB  - The deep inferior epigastric perforator (DIEP) flap can be used to cover large
      defects of the proximal lower extremity, abdominal wall, perineum, vulva, and
      buttock. Pre-expanding DIEP flaps cause a possible delay phenomenon improving
      vascularity, decrease donor site morbidity, and increase the area that can be
      covered. Pre-expansion requires staged procedures, has risk of extrusion and
      infection, causes temporary contour deformity during the expansion process, and
      requires a longer course. Pre-expanded DIEP flaps can be a useful flap with
      proper patient selection and planning.

PMID- 27894572
TI  - Pre-expanded Brachial Artery Perforator Flap.
AB  - The medial upper arm flap is a time-honored yet ignored technique. It may be
      revitalized by combining the techniques of tissue expansion and perforator flap
      surgery. Pre-expansion increases flap dimension, remodels flap vasculature, and
      reduces donor site morbidities, making the medial arm flap a more effective
      option for various defect reconstructions. A pre-expanded brachial artery
      perforator flap achieves excellent functional and aesthetic outcomes in patients
      with soft tissue defects on the head and neck, axilla, chest wall, and upper
      extremity. Although this technique requires multiple procedures, each operation
      is relatively simple and has a low complication rate when properly performed.

PMID- 27894574
TI  - An Overview of Pre-expanded Perforator Flaps: Part 2, Clinical Applications.
AB  - Pre-expanded perforator flaps have several advantages over their traditional
      counterparts owing to the thin, more pliable nature, larger size, and minimum
      morbidity of the donor site. Recently, plastic surgeons have begun to use pre
      expanded perforator flaps to reconstruct defects of almost the entire body,
      including the cervicofacial region, axilla, trunk, and extremities resulting from
      scar, congenital melanocytic nevi, hemangiomas, and neurofibromas. Such a
      versatile flap is especially appropriate for face and neck resurfacing, which
      requires more optimal functional and cosmetic outcomes.

PMID- 27894573
TI  - Pre-expanded Anterolateral Thigh Perforator Flap for Phalloplasty.
AB  - The anterolateral thigh (ALT) perforator flap for phalloplasty is gaining
      popularity because it avoids the well-known scars of the radial forearm flap.
      However, scars are not eliminated, just moved to a different location, the thigh,
      that can for some patients be of great sexual value. Preexpansion of the ALT flap
      allows primary donor site closure, thus avoiding not only the unsightly
      appearance of a skin grafted ALT donor site, but also the skin graft donor site
      scar. Preoperative perforator location by means of computed tomography
      angiography allows safe expander placement through 2 small remote incisions.

PMID- 27894575
TI  - Pre-expanded Free Perforator Flaps.
AB  - Pre-expanded perforator flaps are the most recent technical way to shape tissue
      for exact needs. Reconstruction with pre-expanded free perforator flaps has
      proven successful in terms of obtaining more extensive, more pliable, and thinner
      flaps that have increased vascularity, and also causing less donor site
      morbidity. In this article the author's experience with the clinical application
      of such flaps and the relevant published literature are reviewed.

PMID- 27894576
TI  - Pre-expanded Bipedicled Supratrochlear Perforator Flap for Simultaneous
      Reconstruction of the Nasal and Upper Lip Defects.
AB  - The double "S" principle should be followed for facial reconstruction: the
      "similarity" of the donor site to the defect area and the reconstruction should
      be based on the different "subunits" of the face. In this article the pre
      expanded, bipedicled supratrochlear perforator flap method is described, which is
      used for the resurfacing of both nasal and upper lip defects. This method can
      provide 2 independent flaps with sufficient tissue from 1 single donor site,
      resurfacing the nasal and upper lip units separately and providing an
      unparalleled color and texture match and ideal reconstructive result.

PMID- 27894577
TI  - Pre-expanded, Prefabricated Monoblock Perforator Flap for Total Facial
      Resurfacing.
AB  - In this article, we present the pre-expanded, prefabricated supercharged
      cervicothoracic monoblock perforator flap for total or subtotal facial
      resurfacing. This technique can be a reliable reconstruction option for extensive
      facial skin defect with undamaged muscles and deep structures, which could
      provide excellent aesthetic and functional outcomes with acceptable
      complications. Our approach may replace a conventional "skin-only" face
      allotransplantation in selected patients.

PMID- 27894578
TI  - Pre-expanded and Prefabricated Abdominal Superthin Skin Perforator Flap for Total
      Hand Resurfacing.
AB  - Reconstruction of the postburn hand remains a challenge for surgeons. For
      cosmetic and functional requirements, the desired flap should be thin enough to
      ensure the flexibility of the hand. Conventional perforator flaps serve as a
      viable option when reconstructing the postburn hand to regain functionality.
      However, limitations include the discrepancy in tissue thickness and the
      difficulty with donor site closure. Thus, a preexpanded superthin skin perforator
      flap is an ideal choice for postburn hand reconstruction, with the trade-off
      being a longer treatment course (3-4 months), but with results that satisfy both
      patients and their surgeons.

PMID- 27894579
TI  - Future Perspectives of Pre-expanded Perforator Flaps.
AB  - Although clinical application of a pre-expanded perforator flap is primarily
      focused on face and neck reconstructions, such a flap has also been used to
      reconstruct defects in the trunk, extremities, or hands. With better
      understanding of the improved blood supply to the flap and the mechanism on the
      prefabrication of blood supply within the flap, the pre-expanded perforator flap
      will definitely play a more important role in reconstructive surgery and can be
      used in selected patients by many plastic surgeons worldwide with good
      reconstructive and cosmetic outcomes.

PMID- 27894581
TI  - Pre-expanded Super-Thin Skin Perforator Flaps.
AB  - Patients with severe postburn scar contractures underwent reconstruction of skin
      defects after scar excision with pre-expanded super-thin skin perforator flaps
      supplied primarily by perforators via the "bridging effect" from the branches of
      the adjacent arteries as 2-stage procedures. Pre-expansion is an innovative
      technique and may improve the anastomoses between subdermal vascular plexuses and
      extend the supplying area of these vessels to the flap. Such a flap becomes super
      thin, but with a prefabricated blood supply it can be used for reconstruction of
      skin defects of the face, neck, or other body part with improved functional and
      cosmetic outcomes.

PMID- 27894580
TI  - Imaging Studies for Preoperative Planning of Perforator Flaps: An Overview.
AB  - The vascular anatomy of perforators varies between individuals; thus, accurate
      preoperative assessment of perforators is essential for safely planning
      perforator flaps. Perforator computed tomographic angiography (P-CTA) with
      multidetector-row computed tomography (MDCT) is one of the best available methods
      to precisely reveal the 3-dimensional anatomic details of perforators. The aim of
      this report is to describe the authors' experience using P-CTA with MDCT for
      detecting the perforating vessel preoperatively and a step-by-step approach to
      harvest perforator flaps based on this technique. This report also provides a
      comprehensive review of literature on other preoperative assessment tools of
      perforators.

PMID- 27894583
TI  - Pre-expanded Supraclavicular Artery Perforator Flap.
AB  - The supraclavicular artery perforator (SAP) flap is a versatile flap for the
      reconstruction of head and neck defects. Recently, the authors have modified the
      SAP flap by using an anterior branch of the transverse cervical artery. The
      anterior SAP flap allows the harvest of a tissue island in the deltopectoral
      fossa, which is even thinner, is more pliable, and shows a superior color match
      to the face and neck compared with the original SAP flap. Pre-expansion increases
      flap size considerably, enabling the coverage of extended defects without the
      need of microsurgery.

PMID- 27894582
TI  - Pre-expanded Transverse Cervical Artery Perforator Flap.
AB  - The face and neck are important areas for function and appearance. High-quality
      skin flaps should be used to reconstruct defects in the cervicofacial region.
      This article introduces the pre-expanded transverse cervical artery perforator
      flap, which can be used for cervicofacial reconstruction after burns, trauma, and
      tumor resection with excellent results. This perforator flap is one of the best
      options for cervicofacial reconstruction in terms of color and texture match, and
      has fewer flap complications. With regard to the expanded flap, the donor site
      can be sutured directly leaving only an inconspicuous linear scar.

PMID- 27894584
TI  - Pre-expanded Internal Mammary Artery Perforator Flap.
AB  - Internal mammary artery (IMA)-based pedicled perforator flaps can be used to
      reconstruct defects of the neck and anterior chest wall. Pre-expansion causes a
      possible delay phenomenon, improves flap survival, and decreases donor site
      morbidity. It also increases the area that can be covered. Pre-expanding can
      allow for perforator flaps that require a shorter arc of rotation. The pre
      expanded internal mammary artery perforator (IMAP) flap is an excellent option
      for patients who have undergone multiple failed reconstructions and require large
      amounts of soft tissue while lacking other donor sites.

PMID- 27894585
TI  - Pre-expanded Intercostal Perforator Super-Thin Skin Flap.
AB  - This article introduces pre-expanded super-thin intercostal perforator flaps,
      particularly the flap that has a perforator from the first to second intercostal
      spaces. The key techniques, advantages and disadvantages, and complications and
      management of this flap are described. At present, the thinnest possible flap is
      achieved by thinning the pre-expanded flap that has a perforator from the first
      to second intercostal spaces. It is used to reconstruct large defects on the face
      and neck, thus restoring function and cosmetic appearance.

PMID- 27894587
TI  - Pre-expanded Paraumbilical Perforator Flap.
AB  - The paraumbilical perforator flap is the first and the most famous perforator
      flap. Pre-expansion increases the flap dimension and reduces the flap thickness
      and donor site morbidities, making the paraumbilical perforator flap a more
      effective option for upper extremity reconstruction. Pre-expanded pedicled
      paraumbilical perforator flaps can achieve excellent function and aesthetic
      outcomes in patients with extensive scar contracture and giant melanocytic nevi
      in the upper extremity. Although this technique requires multiple procures, each
      operation is relatively simple and has a low complication rate, when properly
      planned and performed.

PMID- 27894586
TI  - Pre-expanded Thoracodorsal Artery Perforator Flap.
AB  - The size of the thoracodorsal artery perforator (TDAP) flap or pedicle, in
      general, may be found to be inadequate. Pre-expansion of the flap before harvest
      can be a solution to increase the size of the TDAP flap in such instances. The
      pre-expanded TDAP flap can be used to reconstruct large-sized defects with the
      advantage of primary closure of the donor site. This article presents details on
      the surgical technique and provides discussion of the authors' experiences.

PMID- 27894588
TI  - Pre-expanded Perforator Flaps.

PMID- 27894591
TI  - Prehospital fast track care for patients with hip fracture: Impact on time to
      surgery, hospital stay, post-operative complications and mortality a randomised,
      controlled trial.

PMID- 27894592
TI  - [Humanised infrastructure in the ICU. A challenge within our reach].

PMID- 27894590
TI  - Preconditioning with Azadirachta indica ameliorates cardiorenal dysfunction
      through reduction in oxidative stress and extracellular signal regulated protein
      kinase signalling.
AB  - BACKGROUND: Azadirachta indica is widely distributed in Africa, Asia and other
      tropical parts of the world. A. indica (AI) is traditionally used for the
      treatment of several conditions including cancer, hypertension, heart diseases
      and skin disorders. Intestinal ischaemia-reperfusion is a common pathway for many
      diseases and may lead to multiple organ dysfunction syndrome and death.
      OBJECTIVE: In this study, we investigated the ameliorative effects of AI on
      intestinal ischaemia-reperfusion injury-induced cardiorenal dysfunction.
      MATERIALS AND METHODS: Sixty rats were divided into 6 groups; each containing 10.
      Corn oil was orally administered to group A (control) rats for 7 days without
      intestinal ischaemia-reperfusion injury. Group B underwent intestinal ischaemia
      reperfusion injury (IIRI) without any pre-treatment. Groups C, D, E and F were
      pre-treated orally for 7 days with 100 mg/kg AI (100 and (200 mg/kg) vitamin C
      (100 and 200 mg/kg) respectively and thereafter underwent IIRI on the 8th day.
      RESULTS: The cardiac and renal hydrogen peroxide increased significantly whereas
      serum xanthine oxidase and myeloperoxidase levels were significantly elevated (p
      < 0.05) in IIRI only when compared to the control. The cardiac and renal reduced
      glutathione, glutathione peroxidase, protein thiol, non-protein thiol and serum
      nitric oxide (NO) decreased (p < 0.05) significantly following IIRI.
      Immunohistochemical evaluation of cardiac and renal tissues showed reduced
      expressions of the extracellular signal regulated kinase (ERK1/2) in rats with
      IIRI only. However, pre-treatment with A. indica and vitamin C significantly
      reduced markers of oxidative stress and inflammation together with improvement in
      antioxidant status. Also, reduced serum NO level was normalised in rats pre
      treated with A. indica and vitamin C with concomitant higher expressions of
      cardiac and renal ERK1/2. CONCLUSIONS: Together, A. indica and vitamin C
      prevented IRI-induced cardiorenal dysfunction via reduction in oxidative stress,
      improvement in antioxidant defence system and increase in the ERK1/2 expressions.
      Therefore, A. indica can be a useful chemopreventive agent in the prevention and
      treatment of conditions associated with intestinal ischaemia-reperfusion injury.

PMID- 27894593
TI  - Scleromyxoedema.

PMID- 27894589
TI  - Discovery and preclinical evaluation of 7-benzyl-N-(substituted)-pyrrolo[3,2
      d]pyrimidin-4-amines as single agents with microtubule targeting effects along
      with triple-acting angiokinase inhibition as antitumor agents.
AB  - The utility of cytostatic antiangiogenic agents (AA) in cancer chemotherapy lies
      in their combination with cytotoxic chemotherapeutic agents. Clinical
      combinations of AA with microtubule targeting agents (MTAs) have been
      particularly successful. The discovery, synthesis and biological evaluations of a
      series of 7-benzyl-N-substituted-pyrrolo[3,2-d]pyrimidin-4-amines are reported.
      Novel compounds which inhibit proangiogenic receptor tyrosine kinases (RTKs)
      including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet
      derived growth factor receptor-beta (PDGFR-beta) and epidermal growth factor
      receptor (EGFR), along with microtubule targeting in single molecules are
      described. These compounds also inhibited blood vessel formation in the chicken
      chorioallantoic membrane (CAM) assay, and some potently inhibited tubulin
      assembly (with activity comparable to that of combretastatin A-4 (CA)). In
      addition, some of the analogs circumvent the most clinically relevant tumor
      resistance mechanisms (P-glycoprotein and beta-III tubulin expression) to
      microtubule targeting agents (MTA). These MTAs bind at the colchicine site on
      tubulin. Two analogs displayed two to three digit nanomolar GI50 values across
      the entire NCI 60 tumor cell panel and one of these, compound 7, freely water
      soluble as its HCl salt, afforded excellent in vivo antitumor activity against an
      orthotopic triple negative 4T1 breast cancer model and was superior to
      doxorubicin.

PMID- 27894594
TI  - Alterations of Golgi organization in Alzheimer's disease: A cause or a
      consequence?
AB  - The Golgi apparatus is a central organelle of the secretory pathway involved in
      the post-translational modification and sorting of lipids and proteins. In
      mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized
      in polarized manner, which are interconnected by membrane tubules to constitute
      the Golgi ribbon, located in the proximity of the centrosome. Besides the
      processing and transport of cargo, the Golgi complex is actively involved in the
      regulation of mitotic entry, cytoskeleton organization and dynamics, calcium
      homeostasis, and apoptosis, representing a signalling platform for the control of
      several cellular functions, including signalling initiated by receptors located
      at the plasma membrane. Alterations of the conventional Golgi organization are
      associated to many disorders, such as cancer or different neurodegenerative
      diseases. In this review, we examine the functional implications of modifications
      of Golgi structure in neurodegenerative disorders, with a focus on the role of
      Golgi fragmentation in the development of Alzheimer's disease. The comprehension
      of the mechanism that induces Golgi fragmentation and of its downstream effects
      on neuronal function have the potential to contribute to the development of more
      effective therapies to treat or prevent some of these disorders.

PMID- 27894596
TI  - New perspectives on lysosomes in ageing and neurodegenerative disease.

PMID- 27894595
TI  - Do visual illusions affect grasping? Considerable progress in a scientific
      debate. A reply to Whitwell & Goodale, 2016.

PMID- 27894597
TI  - Unexpected Cardiac Death During Anaesthesia of a Young Rabbit Associated with
      Fibro-fatty Replacement of the Right Ventricular Myocardium.
AB  - A 6-month-old female pet rabbit was presented for routine ovariectomy. The pre
      anaesthetic evaluation was unremarkable and no anaesthetic complications occurred
      during the procedure. However, at the end of the surgery, the rabbit suddenly
      showed acute bradycardia and cardiac death. Necropsy examination revealed marked
      dilation of the right ventricle, associated with diffuse thinning of the right
      ventricular free wall. Gross and histopathological findings were suggestive of a
      congenital dilated cardiomyopathy characterized by fibro-fatty replacement of the
      right ventricular myocardium. Similar myocardial lesions have not been previously
      described in rabbits, although they have been documented in myocardial diseases
      of man, dogs, cats, cattle, horses and chimpanzees.

PMID- 27894598
TI  - The Research Practicum and International Research Interdisciplinary School (IRIS)
      initiatives: In memory of Professor Galen S. Wagner M.D., PhD.

PMID- 27894599
TI  - Overexpression of the homologous lanosterol synthase gene in ganoderic acid
      biosynthesis in Ganoderma lingzhi.
AB  - Ganoderic acids (GAs) in Ganoderma lingzhi exhibit anticancer and antimetastatic
      activities. GA yields can be potentially improved by manipulating G. lingzhi
      through genetic engineering. In this study, a putative lanosterol synthase (LS)
      gene was cloned and overexpressed in G. lingzhi. Results showed that its
      overexpression (OE) increased the ganoderic acid (GA) content and the
      accumulation of lanosterol and ergosterol in a submerged G. lingzhi culture. The
      maximum contents of GA-O, GA-Mk, GA-T, GA-S, GA-Mf, and GA-Me in transgenic
      strains were 46.6 +/- 4.8, 24.3 +/- 3.5, 69.8 +/- 8.2, 28.9 +/- 1.4, 15.4 +/-
      1.2, and 26.7 +/- 3.1 MUg/100 mg dry weight, respectively, these values being 6.1
      , 2.2-, 3.2-, 4.8-, 2.0-, and 1.9-times higher than those in wild-type strains.
      In addition, accumulated amounts of lanosterol and ergosterol in transgenic
      strains were 2.3 and 1.4-fold higher than those in the control strains,
      respectively. The transcription level of LS was also increased by more than five
      times in the presence of the G. lingzhi glyceraldehyde-3-phosphate dehydrogenase
      gene promoter, whereas transcription levels of 3-hydroxy-3-methylglutaryl
      coenzyme A enzyme and squalene synthase did not change significantly in
      transgenic strains. This study demonstrated that OE of the homologous LS gene can
      enhance lanosterol accumulation. A large precursor supply promotes GA
      biosynthesis.

PMID- 27894600
TI  - Reply letter to "Texture analysis of parotid gland as a predictive factor of
      radiation induced xerostomia: A subset analysis".

PMID- 27894602
TI  - Evolution and degree of control of cardiovascular risk factors after 5 years of
      follow-up and their relationship with the incidence of peripheral arterial
      disease: ARTPER cohort.
AB  - BACKGROUND AND OBJECTIVE: Although cardiovascular risk factors (CVRF) are well
      known, their degree of control is not optimal. The aim of this study is to assess
      the evolution and control of CVRFs after 5 years of monitoring a population-based
      cohort and their association with the incidence of peripheral arterial disease
      (PAD). MATERIAL AND METHOD: Prospective cohort study recruited between 2006-2008.
      Second phase between 2011-2012. An ankle brachial index was determined for all
      participants in both phases. Demographic variables, CVRF and previous
      cardiovascular events, blood pressure, total cholesterol and its fractions (HDL,
      LDL), triglycerides, glucose and glycosylated hemoglobin levels in diabetic
      patients and the cardiovascular risk score according to the REGICOR table were
      recorded. RESULTS: A total of 2,125 individuals were analyzed. We observed an
      increase in the prevalence of hypertension (HT) (15.4%), diabetes (DM) (8.2%) and
      hypercholesterolemia (20.4%), with no changes in obesity and smoking. The
      cardiovascular risk determined on the basis of the REGICOR table remained at
      around 5.5%. We observed an increased control of CVRF throughout the follow-up
      period, except in the case of DM and obesity. In the multivariate analysis,
      uncontrolled HT 2-folded the risk of onset of PAD (odds ratio [OR] 2.3; 95%
      confidence interval [95% CI] 1.3-4.1), whereas smoking 5-folded this risk (OR
      5.0; 95% CI 2.5-10.2). CONCLUSIONS: Smoking and uncontrolled HT increase the risk
      of onset of PAD in this population. Despite the increase in drug treatments, the
      control of CVRFs continues to be suboptimal.

PMID- 27894603
TI  - Lactic acidosis as an infrequent manifestation of a pheocromocytoma.

PMID- 27894601
TI  - Treatment Rationale and Study Design for the RELAY Study: A Multicenter,
      Randomized, Double-Blind Study of Erlotinib With Ramucirumab or Placebo in
      Patients With Epidermal Growth Factor Receptor Mutation-Positive Metastatic Non
      Small-Cell Lung Cancer.
AB  - INTRODUCTION: We present the treatment rationale and study design for the RELAY
      study (NCT02411448 ). This phase Ib/III study will assess safety, tolerability,
      and efficacy of the combination of ramucirumab with erlotinib in previously
      untreated stage IV non-small-cell lung cancer patients with an activating
      epidermal growth factor receptor (EGFR) mutation. PATIENTS AND METHODS: The study
      is being conducted in approximately 120 sites in North America, Europe, and Asia
      and is currently open for enrollment. In part A (phase Ib), approximately 12
      patients will receive ramucirumab (10 mg/kg) every 2 weeks with erlotinib (150
      mg) every day. Dose-limiting toxicity will be assessed during 2 cycles (4 weeks)
      of treatment. In part B (phase III), approximately 450 patients will be
      randomized in a 1:1 ratio to receive ramucirumab or placebo every 2 weeks with
      erlotinib daily until disease progression, unacceptable toxicity, or other
      withdrawal criteria are met. The primary end point is progression-free survival,
      on the basis of investigator assessment. Secondary end points include overall
      survival, objective response rate, disease control rate, duration of response,
      safety, and quality of life. CONCLUSION: Erlotinib with ramucirumab combination
      was chosen because the addition of an antiangiogenic agent, such as ramucirumab,
      would further improve the efficacy of erlotinib, which is a standard of care in
      the first-line treatment of patients with activating EGFR mutations.

PMID- 27894604
TI  - Evaluation of the efficacy of therapeutic endoscopy in gastrointestinal bleeding
      secondary to angiodysplasias.
AB  - INTRODUCTION: Gastrointestinal angiodysplasias are defined as vascular dilations
      that communicate capillaries and veins in the walls of the digestive tract. The
      clinical presentation of these lesions varies from chronic occult bleeding to
      severe gastrointestinal hemorrhage. AIM: The primary aim of our study was to
      analyze lesion location, the efficacy of therapeutic endoscopy with argon plasma
      coagulation, and the factors associated with rebleeding in patients with
      gastrointestinal angiodysplasias. MATERIAL AND METHODS: A retrospective study of
      32,042 endoscopies was carried out within the time frame of January 2012 and
      December 2013 at our hospital center. Gastrointestinal angiodysplasia was the
      diagnosis in 331 of the endoscopies. The procedures included upper
      gastrointestinal endoscopy, colonoscopy, sigmoidoscopy, and enteroscopy. RESULTS:
      The most frequent location of the angiodysplasias was the cecum (49%), followed
      by the ascending colon (17%) and the sigmoid colon (16%). They were most
      frequently found in the duodenum (60%) and gastric body (49%) at upper
      gastrointestinal endoscopy. Therapeutic endoscopy was performed in 163 cases
      (49.8%) and the most predominant methods were fulguration with argon (90%) and
      combination treatment (argon plasma coagulation and injection sclerotherapy)
      (6.7%). The macroscopic rebleeding rate after therapeutic endoscopy was 7.4%.
      Patients that had rebleeding presented with a lower hemoglobin concentration,
      higher mean age, and the presence of multiple angiodysplasias at endoscopy
      (P<.05). CONCLUSIONS: Therapeutic endoscopy was performed in 49.8% of the
      patients with angiodysplasias. The macroscopic rebleeding rate after treatment
      was 7.4%. There were statistically significant differences in the patients with
      rebleeding in relation to mean age, hemoglobin values, and the presence of
      multiple angiodysplasias.

PMID- 27894605
TI  - Polypoid nodular scar after endoscopic submucosal dissection in the gastric
      antrum.

PMID- 27894606
TI  - Uncomfortable trade-offs: Canadian policy makers' perspectives on setting
      objectives for their health systems.
AB  - BACKGROUND: Although a wide range of health system performance indicators are
      commonly reported on, there has been little effort to establish their relevance
      to the objectives that health systems actually pursue. OBJECTIVE: The aim of this
      study was to identify, explore and better understand health policy makers' views
      regarding the objectives and outcomes for their health systems, how they are
      prioritized, and the underlying processes that yield them to inform the
      development of health system efficiency measures. METHODS: A descriptive,
      qualitative methodology was employed using key informant interviews with 17
      current and former senior health ministry officials in 8 Canadian provinces and 2
      territories. KEY FINDINGS: Health ministries have clearly stated objectives for
      health systems focused on the achievement of health system delivery and
      population health goals and, increasingly, public, patient and financial
      accountability. Acute care objectives are routinely prioritized over population
      health objectives and viewed as resulting from challenges associated with
      difficult trade-off decisions shaped by organized interests and the media rather
      than explicit, evidence-based processes. CONCLUSION: This study provides insights
      beyond publicly available documents to explore the processes that underlie simple
      statements of health system objectives. Our findings suggest that despite
      respondents giving priority to improving individual and population health, it is
      more commonly portrayed as an ideal objective than as a realistic one. By
      understanding what lies behind statements about what health systems are striving
      for, we offer a more robust avenue for increasing the uptake of future studies of
      health system performance.

PMID- 27894607
TI  - Exosomes in lung cancer liquid biopsies: Two sides of the same coin?

PMID- 27894608
TI  - Brucellosis in cattle and micro-scale spatial variability of pastoral household
      income from dairy production in south western Uganda.
AB  - Brucellosis in cattle and humans has received world-wide research attention as a
      neglected and re-emerging zoonotic disease with many routes of transmission.
      Studies of brucellosis in Uganda have emphasized occupational exposures and also
      revealed variations in prevalence levels by region and cattle production systems.
      To date, research linking pastoralist household income from dairy production to
      brucellosis and its transmission risk pathways do not exist in Uganda. We
      assessed whether spatial differences in unit milk prices can be explained by
      brucellosis prevalence in cattle along a distance gradient from Lake Mburo
      National Park in Uganda. Semi-structured interviews administered to 366 randomly
      selected household heads were supplemented with serological data on brucellosis
      in cattle. Statistical analysis included Pearson correlation test, multiple
      regression and analysis of variance (ANOVA) using SPSS version 17. Serological
      results showed that 44% of cattle blood samples were sero-positive for
      brucellosis. The results obtained from interviews put the statistical mean of
      household reported cattle abortions at 5.39 (5.08-5.70 at 95% CI, n=366). Post
      hoc analysis of variance revealed that both sero-positive cattle and reported
      cattle abortions significantly were much lower when moving outwards from the park
      boundary (p<0.05), while the price of milk increased significantly (p<0.05) along
      the same distance gradient. Further studies should identify public and private
      partnerships needed to create and strengthen good zoonotic brucellosis management
      practices at the nexus of wildlife and livestock in Uganda.

PMID- 27894609
TI  - What is the problem with medically unexplained symptoms for GPs? A meta-synthesis
      of qualitative studies.
AB  - OBJECTIVE: To gain a deeper understanding of challenges faced by GPs when
      managing patients with MUS. METHODS: We used meta-ethnography to synthesize
      qualitative studies on GPs' perception and management of MUS. RESULTS: The
      problem with MUS for GPs is the epistemological incongruence between dominant
      disease models and the reality of meeting patients suffering from persistent
      illness. GPs have used flexible approaches to manage the situation, yet patients
      and doctors have had parallel negative experiences of being stuck, untrustworthy
      and helpless. In the face of cognitive incongruence, GPs have strived to achieve
      relational congruence with their patients. This has led to parallel positive
      experiences of mutual trust and validation. With more experience, some GPs seem
      to overcome the incongruences, and later studies point towards a reframing of the
      MUS problem. CONCLUSION: For GPs, the challenge with MUS is most importantly at
      an epistemological level. Hence, a full reframing of the problem of MUS for GPs
      (and for patients) implies broad changes in basic medical knowledge and
      education. PRACTICE IMPLICATIONS: Short-term: Improve management of patients with
      MUS by transferring experience-based, reality-adjusted knowledge from senior GPs
      to juniors. Long-term: Work towards new models of disease that integrate
      knowledge from all relevant disciplines.

PMID- 27894610
TI  - [Reconstruction of proximal nasal defect after deep carcinological resection.
      Interest to combine titane mesh with fat grafting].
AB  - INTRODUCTION: The mucosal cylindroma or adenoid cystic carcinoma is the second
      sinonasal non-epithelial malignant tumor frequency argument. Due to the
      achievement of the nasal mucosa and a late diagnosis reconstructions are often
      complex. We report the case of a mucous cylindroma recurrence of nasal septum
      requiring a wide and deep excision of the root of the nose with nasal
      reconstruction. CASE REPORT: A patient aged 66 years whose history resection two
      years ago with a mucous adenoid cystic carcinoma of the right side of the nasal
      septum, had a local recurrence T2NOM0 imposing a wide excision with amputation
      nasal septum own bones of nose, the anterior portion of the triangular
      cartilages. The reconstruction was carried out in three areas: a musculocutaneous
      forehead flap to the mucosal level, a titanium plate to the bone plane, nasal
      native skin to skin level. Histological examination confirmed the existence of a
      recurrence cylindroma infiltrating the bone. The surgical margins were however in
      sano. Adjuvant radiotherapy to 60Gy dose of the surgical area was indicated after
      surgery. The consequences of surgery and radiotherapy were simple. However local
      changes to show a progressive refinement of the nasal skin due to irradiation
      leading to a small titanium plate exposure revision surgery with coverage by a
      glabellar flap associated with a time of lipomodeling unexposed areas have
      improved and trophism of soft tissue. Two further lipomodeling sessions have
      yielded a good quality and stable skin. From an oncological point of view, no
      recurrence was detected with a decline of 10 years. Aesthetic and functional
      point of view the results were highly satisfactory. DISCUSSION: Oncologic
      resections subtotal nasal pyramid are complex, we will see the benefits and
      disadvantages of the different techniques used in the different stages.
      CONCLUSION: This case report illustrates the difficulties of reconstruction after
      wide excision of mucosal lesions root of the nose carrying the mucous plan and
      nasal bones. It stresses the importance of bone reconstruction titanium plate and
      innovative element, the efficiency of fat transfer to restore the quality and
      trophicity soft tissue. Fat transfer in addition to reconstructions by titanium
      plates and splints may thus expand the indications of these types of techniques
      in complex facial and cranial reconstructions.

PMID- 27894611
TI  - The Threshold Theory for Parkinson's Disease.
AB  - Parkinson's disease (PD) is recognized by the accumulation of alpha-synuclein
      within neurons. In contrast to the current ascending theory where alpha-synuclein
      would propagate from neuron to neuron, we now propose the threshold theory for PD
      based on evidence of parallel degeneration of both central nervous system (CNS)
      and peripheral nervous system (PNS) in PD. The functional threshold is lower for
      the emergence of early symptoms before the classical motor symptoms of PD. This
      is due to the larger functional reserve of the midbrain dopamine and integrated
      basal ganglia motor systems to control movement. This threshold theory better
      accounts for the current neurobiology of PD symptom progression compared to the
      hypothesis that the disease ascends from the PNS to the CNS as proposed by
      Braak's hypothesis.

PMID- 27894613
TI  - Comparative study between thulium laser (Tm: YAG) 150W and greenlight laser
      (LBO:ND-YAG) 120W for the treatment of benign prostatic hyperpplasia: Short-term
      efficacy and security.
AB  - OBJECTIVE: To compare the results of efficacy and safety of Thulium laser 150W
      against Greenlight laser 120W in the treatment of short term benign prostatic
      hyperplasia (12 months after surgery). MATERIAL AND METHODS: This is a
      retrospective observational study where men who underwent the surgical technique
      of prostate vaporization over a period of four years in our center are included.
      The homogeneity of the sample was checked, and postoperative complications (acute
      urinary retention, reentry, need for transfusion), failures per year of surgery
      (reoperation, peak flow <15ml/sec, no improvement in comparing the I-PSS), and
      decreased PSA were compared a year after surgery. A bivariate analysis using Chi
      square and t-Student was carried out. RESULTS: 116 patients were treated with
      thulium and 118 with green laser. The sample was homogeneous for preoperative
      variables (P>.05). No differences in complications were observed: in urine acute
      retention, 4.3% with thulium and 6.8% with green laser (P=.41); in readmissions,
      2.6% with thulium and 1.7% with green laser (P=.68); in need for transfusion,
      2.6% with thulium and 0% with green laser (P=.12). No differences were observed
      in the percentage of patients reoperation (1.7% in the group of thulium, 5.1% in
      the green laser, P=.28); or in individuals with Qmax less than 15ml/sec (6.9%
      with thulium, 6.77% with green laser, P=.75), or in the absence of improvement in
      the IPSS (5, 2% with thulium, 3.4% with green laser, P=.65). There was also no
      difference in the levels of PSA in ng/mL a year after surgery: with thulium
      2.78+/-2.09 and with green laser 1.83+/-1.48 (P=.75). CONCLUSIONS: Prostate
      vaporization with thulium laser 150W is comparable to that made with green laser
      120W for the treatment of lower urinary tract symptoms caused by BPH, being both
      effective and safe techniques to 12 months after surgery. Future prospective
      randomized studies are needed to confirm this conclusion on both techniques.

PMID- 27894612
TI  - Influence of social networks on congresses of urological societies and
      associations: Results of the 81th National Congress of the Spanish Urological
      Association.
AB  - OBJECTIVE: To measure social network activity during the 81th National Congress
      of the Spanish Urological Association (AEU) and to compare it with the activity
      during other congresses of national and international urological associations.
      MATERIAL AND METHODS: We designed and registered the official hashtag #AEU16 for
      the 81th National Congress of the AEU on the Symplur website. The following
      measurements were recorded: number of participants, number of tweets, tweets by
      participant, tweets per hour and views. RESULTS: The number of participants in
      the social network activity during the congress was 207. The measurements of
      activity in Twitter consisted of a total of 1866 tweets, a mean rate of 16
      tweets/h, 9 tweets per participant and 1,511,142 views. The activity during the
      international congresses is as follows: 2016 American Urological Association
      annual congress (views: 28,052,558), 2016 European Association of Urology annual
      congress (views: 13,915,994), 2016 Urological Society of Australia and New
      Zealand (views: 4,757,453), 2015 Societe Internationale d'Urologie annual
      congress (views: 1,023,038). The activity during the national congresses was
      recorded as follows: 2016 Annual Conference of The British Association of
      Urological Surgeons (views: 2,518,880), 81th National Congress of the AEU (views:
      1,511,142), 109th Congress of l'Association Francaise d'Urologie (views:
      662,828), 67th German Congress of Urology (views: 167,347). We found 10 posts in
      Facebook and 2 communications via Periscope TV related to #AEU16. CONCLUSIONS:
      The social network activity during the 81th National Congress of the AEU was
      notable given the results of this study. The use of social networks has expanded
      among urological associations, congresses and meetings, giving them a global
      character.

PMID- 27894614
TI  - Giant vulvar verruciform xanthoma can mimic a common vulvar mass, genital warts.

PMID- 27894615
TI  - Opioid dependence and pregnancy: minimizing stress on the fetal brain.

PMID- 27894616
TI  - Histopathological lesions in encephalon and heart of mice infected with
      Toxoplasma gondii increase after Lycopodium clavatum 200dH treatment.
AB  - In many cases, symptoms of toxoplasmosis are mistaken for the ones of other
      infectious diseases. Clinical signs are rare in immunocompetent people. However,
      when they arise, in the acute phase of infection, several organs are affected due
      to the rapid spread of tachyzoites through the bloodstream. In the present study,
      the reduction of tachyzoites in peripheral blood of mice of G72 (infected 72h
      after treatment) and G48 (infected 48h after treatment and treated three more
      times), when compared with IC (infected and non-treated), suggests protective
      effect exerted by Lycopodium clavatum. If on the one hand L. clavatum brought
      benefits, reducing parasitemia, on the other hand, the parasitism became
      exacerbated. Histopathological analysis demonstrated focal, multifocal and
      diffuse inflammatory infiltrates, ranging from absent, discreet, moderate to
      intense, in heart and encephalon of mice of NIC (non-infected and non-treated),
      IC, G48 and G72 groups, respectively. In the perivascular region and meninges,
      the injuries were enlarged. The presence of tachyzoites was demonstrated through
      immunohistochemical (IHC) assay in myocardium. Toxoplasma gondii induced increase
      of collagen fibers in myocardium of mice of G72 and G48 groups, compared with IC
      (p<0.05) and NIC (p<0.001). The presence of inflammatory infiltrates, as well as
      the progressive fibrosis, caused myocardial remodeling in animals treated with L.
      clavatum. Counterstaining with H&E suggests TGF-beta expression by mononuclear
      cells in the inflammatory infiltrate. Based on our results, we can conclude that
      the adopted regimen and potency exerted a protective effect, reducing
      parasitemia. However, it intensified the histopathological lesions in encephalon
      and heart of mice infected with T. gondii.

PMID- 27894617
TI  - Pathway analysis based on Monte Carlo Cross-Validation in polyarticular juvenile
      idiopathic arthritis.
AB  - INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a common chronic disease
      with onset before the 16 years old in a child. Polyarticular JIA has been
      reported as the main form of JIA in several locations. Until now, understanding
      of the genetic basis of JIA is incomplete. The purpose of this study was to
      identify pathway pairs of great potential functional relevance in the progression
      of polyarticular JIA. MATERIALS AND METHODS: Microarray data of 59 peripheral
      blood samples from healthy children and 61 samples from polyarticular JIA were
      transformed to gene expression data. Differential expressed genes (DEG) between
      patients and normal controls were identified using Linear Models for Microarray
      Analysis. After performed enrichment of DEG, differential pathways were
      identified with Fisher's test and false discovery rate. Differential pathway
      pairs were constructed with random two differential pathways, and were evaluated
      by Random Forest classification. Monte Carlo Cross-Validation was introduced to
      screen the best pathway pair. RESULTS: 42 DEG with P-values<0.01 were identified.
      19 differential pathways with P-values<0.01 were identified. Area under the curve
      (AUC) of pathway pairs was generated with RF classification. After 50 bootstraps
      of Monte Carlo Cross-Validation, the best pathway pair with the highest AUC value
      was identified, and it was the pair of tumoricidal function of hepatic natural
      killer cells pathway and erythropoietin signaling pathway. CONCLUSION: These
      identified pathway pairs may play pivotal roles in the progress of polyarticular
      JIA and can be applied for diagnosis. Particular attention can be focused on them
      for further research.

PMID- 27894618
TI  - Primary pulmonary/pleural melanoma in a 13 year-old presenting as pleural
      effusion.
AB  - Melanoma in children, adolescents, and young adults is uncommon and reported
      almost exclusively as cutaneous melanoma. Melanoma presenting as a pleural
      effusion is very rare in adults and not reported in the pediatric population.
      Additionally, primary pulmonary melanoma is overall very rare and undocumented in
      pediatric patients. Furthermore, the distinction between a primary
      pulmonary/pleural melanoma versus a regressed cutaneous melanoma with
      pulmonary/pleural metastases remains extremely challenging. We discuss a case of
      a previously healthy 13-year-old girl that presented with a left-sided pleural
      effusion. Investigations revealed a large mediastinal mass, left-sided pleural
      and pulmonary nodules, a sacral mass, and bone marrow infiltration. The neoplasm
      was subsequently diagnosed by morphology and immunocytochemistry with
      histological correlation as malignant melanoma. As no mucosal, eye, or cutaneous
      lesions were identified, we deliberate the likelihood of a regressed cutaneous
      melanoma with metastases versus primary pulmonary/pleural melanoma with pleural
      effusion and discuss its diagnostic approach.

PMID- 27894619
TI  - Expression of pro-fibrotic and anti-fibrotic molecules in dimethylnitrosamine
      induced hepatic fibrosis.
AB  - BACKGROUND: Hepatic fibrosis is characterized by a progressive accumulation of
      fibrillar extracellular matrix (ECM) proteins, produced by activated
      myofibroblasts which are modulated by both profibrotic and antifibrotic factors.
      OBJECTIVE: To evaluate in vivo the expression of pro-fibrotic molecules like
      avbeta6 integrin, transforming growth factor-beta (TGF-beta), Smad3, connective
      tissue growth factor (CTGF) and mammalian target of Rapamycin (mTOR), as well as
      anti-fibrotic peroxisome proliferator-activated receptor-gamma (PPARgamma) in an
      experimental model of chronic hepatitis-associated fibrosis induced by
      intraperitoneal administration of dimethylnitrosamine (DMN) in mice. METHODS:
      Chronic hepatitis was induced in 12 Smad3 wild-type (WT) and 12 knock-out (KO)
      mice by intraperitoneal DMN administration. Histological, morphometric and
      immunohistochemical analyses using alpha-smooth muscle actin (alpha-SMA),
      collagen types I-III, TGF-beta1, Smad3, avbeta6 integrin, CTGF, mTOR and
      PPARgamma antibodies were performed. RESULTS: The liver of DMN-treated Smad3 WT
      mice showed a higher degree of hepatic accumulation of connective tissue compared
      to KO mice. The expression of alpha-SMA, collagen I-III and CTGF was increased in
      Smad3 WT compared to KO mice treated with DMN, associated with a concomitant up
      regulation of avbeta6, TGFbeta, Smad3, and mTOR and a reduction in PPARgamma
      expression. CONCLUSIONS: These results suggest a possible interaction between pro
      fibrotic and anti-fibrotic molecules in the development of hepatic fibrosis.

PMID- 27894620
TI  - Clinical implications of a rare renal entity: Pleomorphic Hyalinizing Angiectatic
      Tumor (PHAT).
AB  - Pleomorphic Hyalinizing Angiectatic Tumor (PHAT) is a rare benign lesion
      characterized by slow growth, infiltrative behavior and high rate of local
      recurrences. Only one case has been described in retroperitoneum, at renal hilum,
      but not involving pelvis or parenchyma. Here we present the first case of PHAT
      arising in the renal parenchyma. A nodular lesion in right kidney lower pole was
      diagnosed to a 61 year old woman. The patient underwent right nephrectomy.
      Microscopically, the lesion showed solid and pseudo-cystic components with
      hemorrhagic areas characterized by aggregates of ectatic blood vessels.
      Pleomorphic cells were characterized by large eosinophilic cytoplasm with
      irregular and hyperchromatic nuclei. Immunohistochemistry was performed and the
      lesion was classified as a Pleomorphic Hyalinizing Angiectatic Tumor (PHAT). Due
      to the clinical behavior of this tumor, in spite of its benign nature, review of
      the surgical margins and close follow up after partial nephrectomy are mandatory.

PMID- 27894621
TI  - Glomerulocystic kidney presenting as a unilateral kidney mass in a newborn with
      tuberous sclerosis: Report of a case and review of the literature.
AB  - Glomerular cysts are defined as a 2-3 times dilation of Bowman spaces and their
      presence in at least 5% of the glomeruli defines the kidneys as glomerulocystic
      (GCK). The association between cystic kidney disease and the tuberous sclerosis
      complex (TSC) is well known, but its presentation as a unilateral mass with
      glomerulocystic pattern is rare. We describe a case of an infant with a prenatal
      diagnosis of TSC, with a renal mass that was believed to be a renal tumor. A four
      month-old infant with maternal history of TSC and prenatally diagnosed
      subependymal nodules and a right renal mass underwent nephrectomy. Histopathology
      revealed a segmental GCK with epithelial hyperplasia of the tubules and cysts. A
      diagnosis of TSC associated GCK was rendered. Eight other cases with similar
      histopathological findings were found in the literature, two of which presented
      as a localized mass. Usually there is no family history but the pathologic
      findings are similar. Awareness of the entity and its presentation as a localized
      mass may aid in the differential diagnosis of renal masses in infants. The pre
      operative diagnosis of GCK is difficult and relies on a high degree of clinical
      awareness and imaging skills. Its presence should prompt the search for its
      etiology, particularly the exclusion of a heritable cause. The hyperplastic
      tubular epithelium within the glomerular cysts found in ours and other reported
      cases seems so characteristic that may serve as a major clue for the diagnosis of
      TSC.

PMID- 27894622
TI  - A case of Philadelphia chromosome positive acute lymphoblastic leukemia with
      partial trisomy of chromosome 1q involving chromosome 13 as the acceptor-A novel
      cytogenetic finding.
AB  - The Philadelphia (Ph) chromosome is infrequently found in acute lymphoblastic
      leukemia and is associated with poor prognosis. We present a case of Ph
      chromosome positive B cell-acute lymphoblastic leukemia with the partial trisomy
      of chromosome 1q involving chromosome 13 as the acceptor which has never been
      reported in the English literature. Jumping translocation (JT) of chromosome 1 is
      rare and is associated with disease progression and poor prognosis. Herein, we
      report the first case of Ph chromosome positive B cell-acute lymphoblastic
      leukemia with coexisting jumping translocation of chromosome 1 leading to trisomy
      of chromosome 1q. Dismal prognosis associated with synchronous presence of a Ph
      chromosome and JT leading to a partial trisomy of chromosome 1q may carry
      significant prognostic and therapeutic implications. This may be an incidental
      finding and further studies with large patient cohorts and clinical outcomes are
      needed to definitively determine the predictive value of this cytogenetic
      finding.

PMID- 27894623
TI  - Female With Chest Pain and Nausea.

PMID- 27894624
TI  - Female With Palpitations and Weakness.

PMID- 27894625
TI  - Woman With Lower Back Pain.

PMID- 27894626
TI  - Young Woman With Rash on Left Thigh.

PMID- 27894627
TI  - Life in Death.

PMID- 27894628
TI  - The Scab.

PMID- 27894629
TI  - Hello From the Other Side.

PMID- 27894630
TI  - Finding Factors Associated With Post-Emergency Department Morbidity and Mortality
      in Elderly Patients: Analyzing a Case-Control Study: Answers to the July 2016
      Annals of Emergency Medicine Journal Club.

PMID- 27894631
TI  - Elderly Woman With Altered Mental Status and Hypoxia.

PMID- 27894632
TI  - Adolescent Male With Knee Pain and Swelling.

PMID- 27894633
TI  - Young Child With Abdominal and Back Pain.

PMID- 27894634
TI  - A Clinical Decision Rule for Thoracolumbar Spine Imaging in Blunt Trauma?

PMID- 27894635
TI  - Sepsis-3 Definitions.

PMID- 27894636
TI  - Time-Driven Activity-Based Costing in Emergency Medicine.

PMID- 27894637
TI  - In reply.

PMID- 27894638
TI  - Additional Observations About the Diagnostic Approach to Patients With Headache
      and Possible Subarachnoid Hemorrhage.

PMID- 27894639
TI  - Editorial Oversight of Results Reported in Annals.

PMID- 27894640
TI  - In reply.

PMID- 27894641
TI  - Ethical Use of Telemedicine in Emergency Care.

PMID- 27894642
TI  - Young Male With Neck Pain.

PMID- 27894643
TI  - Young Woman With Paraplegia Following a Motor Vehicle Crash.

PMID- 27894644
TI  - Newborn With Scalp Swelling.

PMID- 27894645
TI  - Microbes Dress for Success: Tolerance or Resistance?
AB  - The intestinal microbiota performs essential functions for host physiology, but
      the specific constituents and the microbial factors required to promote host
      health remain largely unknown. A study by Rangan et al. suggests that members of
      the microbiota can modify microbial associated molecular patterns to promote host
      defense against invading pathogens.

PMID- 27894647
TI  - Addressing addiction in the USA.

PMID- 27894646
TI  - The Enigmatic Esx Proteins: Looking Beyond Mycobacteria.
AB  - Bacteria export proteins across membranes using a range of transport machineries.
      Type VII secretion systems (T7SSs), originally described in mycobacteria, are now
      known to be widespread across diverse bacterial phyla. Recent studies have
      characterized secretion components and mechanisms of type VII secretion in
      pathogenic and environmental bacteria. A variety of functions have been
      attributed to T7SS substrates, including interactions with eukaryotes and with
      other bacteria. Here, we evaluate the growing body of knowledge on T7SSs, with
      focus on the nonmycobacterial systems, reviewing their phylogenetic distribution,
      structure and function in diverse settings.

PMID- 27894648
TI  - Reversing the rising tide of diabetes in China.

PMID- 27894649
TI  - The unacceptable reality of care for people living with dementia.

PMID- 27894650
TI  - New WHO antenatal care model-quality worth paying for?

PMID- 27894652
TI  - Offline: The case against (and for) public health.

PMID- 27894651
TI  - The global shortage of health workers-an opportunity to transform care.

PMID- 27894653
TI  - Targeting HIV prevention to young women in Africa.

PMID- 27894655
TI  - Deborah L Birx: on a mission to end the HIV/AIDS epidemic.

PMID- 27894654
TI  - Government purge continues in Turkey after failed coup.

PMID- 27894656
TI  - Picturing health: stories of stillbirths.

PMID- 27894658
TI  - Gender and health: between nomenclatures and continuums.

PMID- 27894657
TI  - Transgender health in India and Pakistan.

PMID- 27894659
TI  - How successful was the English teenage pregnancy strategy?

PMID- 27894660
TI  - How successful was the English teenage pregnancy strategy? - Authors' reply.

PMID- 27894661
TI  - Brexit-a perspective from the other side of the Channel.

PMID- 27894662
TI  - The challenge of screening for early gastric cancer in China.

PMID- 27894663
TI  - More than meets the eye?

PMID- 27894664
TI  - Tomographic osteometry of the zygomatic bone applied to traumatology of facial
      bones: Preliminary retrospective study of zygomatic summit in 28 patients.
AB  - BACKGROUND: The available referential measures defining the zygomatic bone
      morphology are adequate enough for full determination of the zygoma positioning,
      especially for trauma surgery, but osteometric analysis of the zygoma positioning
      based on tomographic examinations could be useful in peroperative and
      postoperative imaging. In this study, we propose referential measures, taking
      into account the morphology and the symmetry of the zygoma. In addition, the
      reliability and reproducibility are considered. METHODS: Thirty normal computed
      tomography (CT) scans were used to establish the referential measures. The study
      involved preoperative imaging (27 CT and 1 cone beam CT [CBCT] scan), and
      postoperative imaging (6 CT and 22 CBCT scans) pertaining to 28 patients, showing
      a unilateral zygomatic fracture. In a precisely chosen axial cut in the orbito
      meatal plane, 3 referential data were defined: namely, S, denoting the distance
      of the zygoma summit; alphaS, representing the angle between the summit and the
      symmetry axis passing through the clivus; and alphaZ, corresponding to the
      morphologic angle. RESULTS: The 3 referential measures S, alphaS, and alphaZ are
      reliable and reproducible by CT and CBCT examination. Those parameters can be
      used to evaluate the zygomatic symmetry. The postoperative asymmetries arise from
      an erroneous recovery of S, which was statistically significant at p = 0.0216.
      CONCLUSION: On a single optimized axial cut, the new referential measures are
      useful and effective in preoperative and postoperative assessment of the residual
      bone asymmetries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 27894665
TI  - Modulatory effects of curcumin on apoptosis and cytotoxicity-related molecules in
      HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients.
AB  - Apoptosis is a universal cellular defense mechanism against viral infection.
      Curcumin, an anti-inflammatory phytochemical, induces apoptosis through
      mitochondrial and receptor-mediated pathways, as well as activation of caspase
      cascades. Here, we investigated the impact of supplementation with curcumin on
      the expression of a panel of apoptosis- and cytotoxicity-related genes in
      patients suffering from HTLV-1 associated myelopathy/tropical spastic paraparesis
      (HAM/TSP), a progressive demyelinating neuroinflammatory disease caused by HTLV-1
      infection. Twenty-one HAM/TSP patients enrolled in this study. Curcumin
      nanomicelles (80mg/day, orally) were administered once a day for 12 weeks. The
      mRNA levels of total Fas (tFas), membrane-bound Fas (mFas), Fas-Ligand (FasL),
      TNF-related apoptosis-inducing ligand (TRAIL), perforin, granzyme A, granzyme B
      and granulysin were analyzed before and after treatment in peripheral blood
      lymphocytes. Protein levels of Fas, FasL, TRAIL and granulysin were also measured
      in serum using ELISA. Curcumin supplementation inhibited FasL mRNA production and
      up-regulated the expression of pro-apoptotic molecules granzyme A (at the mRNA
      level) and granulysin (at the protein level), suggesting degranulation of
      granulysin-bearing cells following curcumin supplementation. Conversely, Curcumin
      did not affect Fas, TRAIL, perforin, granzyme B at the mRNA level, and anti
      apoptotic molecules sFas, sFasL and sTRAIL at the protein level. The present
      results suggest that curcumin supplementation increases cytotoxicity-related
      molecules granzyme A and granulysin in patients with HAM/TSP.

PMID- 27894666
TI  - Ouabain induces apoptosis and autophagy in Burkitt's lymphoma Raji cells.
AB  - The steroid Na+/K+-ATPase blocker ouabain has been shown to exhibit cytotoxic
      effects in various tumor cell systems. This study aimed to determine the effects
      of ouabain on Burkitt's lymphoma Raji cells. Ouabain treatment of Raji cells
      significantly inhibited cell proliferation in a dose-dependent manner and
      increased the morphological changes associated with apoptosis. Additionally,
      increased numbers of both early and late apoptotic cells were observed by annexin
      V-FITC/PI flow cytometry assay. Increased levels of caspase-3 and cleaved-caspase
      3, higher Bax activity and decreased expression of the anti-apoptotic protein Bcl
      2 were detected in ouabain-treated Raji cells. Vacuole accumulation was also
      observed in transmission electron microscope (TEM) images of ouabain-treated Raji
      cells, indicating that these cells were undergoing autophagy. Expression of the
      autophagy-related proteins LC3-II and Beclin-1 was upregulated in ouabain-treated
      Raji cells. These results suggest that ouabain may promote cell death in Raji
      cells by inducing pathways associated with apoptosis and autophagy. Our study
      also provides novel evidence that ouabain may be an effective agent for treating
      Burkitt's lymphoma.

PMID- 27894667
TI  - Nuclear PKM2 expression, an independent risk factor for ER after curative
      resection of hepatocellular carcinoma.
AB  - Surgical resection, providing a long-term survival of hepatocellular carcinoma
      (HCC) patients, is regarded as one of the standard curative treatments of HCC if
      the tumor is resectable. However, 50% patients develop early recurrence (ER)
      during the first two years after operation, which are more diffuse and rarely
      treatable with unsatisfactory long-term survival. Unfortunately, the underlying
      mechanisms of ER after curative resection and the molecular markers with
      predictive and prognostic significance have never been identified yet. Recent
      studies reveal that pyruvate kinase M2 (PKM2) levels were correlated with overall
      survival and disease-free survival in patients with HCC. The present study was
      aimed to investigate the correlation between the expression of PKM2 and ER. Our
      findings demonstrated that not the total PKM2 expression but the nuclear PKM2
      expression as an independent risk factor for ER after curative resection, and
      could be a promising intervention target following curative resection for HCC
      patients.

PMID- 27894668
TI  - Txn1, Ctsd and Cdk4 are key proteins of combination therapy with taurine,
      epigallocatechin gallate and genistein against liver fibrosis in rats.
AB  - The anti-fibrotic mechanism of combination therapy with taurine, epigallocatechin
      gallate and genistein was studied from the perspective of serum proteomics in our
      previous work. In order to further investigate and systematically analyse other
      possible therapeutic mechanism of combination therapy against liver fibrosis,
      isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis
      was applied to study the protein profile changes in liver tissue of carbon
      tetrachloride-induced liver fibrosis rats after combination therapy. A total of
      115 differentially expressed proteins containing 84 up-regulated and 31 down
      regulated proteins in response to combination therapy were identified. Three
      differentially expressed proteins (Txn1, Ctsd and Cdk4) involved in antioxidant
      defense system and the activation and proliferation of hepatic stellate cell were
      selected for further validation by western blot and real-time PCR analysis. Our
      study highlight the importance of differentially expressed proteins Txn1, Ctsd
      and Cdk4 against liver fibrosis, which may provide a more precise and
      comprehensive perspective for clarifying the roles of combination therapy as a
      potential agent for treatment of liver fibrosis.

PMID- 27894669
TI  - The Role of the Laboratory and Transfusion Service in the Management of Ebola
      Virus Disease.
AB  - The Ebola outbreak that began in 2013 infected and killed record numbers of
      individuals and created unprecedented challenges, including containment and
      treatment of the virus in resource-strained West Africa as well as the
      repatriation and treatment for patients in the United States and Europe. Valuable
      lessons were learned, especially the important role that the laboratory and
      transfusion service plays in the treatment for patients with Ebola virus disease
      (EVD) by providing data for supportive care and fluid resuscitation as well as
      the generation of investigational therapies such as convalescent plasma (CP). To
      provide treatment support, laboratories had to evaluate and update procedures to
      ensure the safety of laboratory personnel. Because there is no licensed EVD
      specific treatment, CP was used in more than 99 patients with only 1 possible
      severe adverse event reported. However, given the biologic variability inherent
      in CP as well as the small number of patient treated in a nonrandomized fashion,
      the efficacy of CP in the treatment of EVD remains unknown.

PMID- 27894671
TI  - Response to Letter to the Editor on "Factors Associated With Trunnionosis in the
      Metal-on-Metal Pinnacle Hip".

PMID- 27894670
TI  - Does Cost-Related Medication Nonadherence among Cardiovascular Disease Patients
      Vary by Gender? Evidence from a Nationally Representative Sample.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is a leading cause of death and
      disability as well as a major burden on the U.S. healthcare system. Cost-related
      medication nonadherence (CRN) to prescribed medications is common among patients
      with CVD. This study examines the gender differences in CRN among CVD patients.
      METHODS: We used 2011 to 2014 data from the National Health Interview Survey, an
      annual, cross-sectional, nationally representative household survey of the
      noninstitutionalized U.S. civilian population (>=18 years of age). Based on
      Andersen's model of health services utilization, multivariate logistic
      regressions were estimated to examine the effect of gender on the primary
      composite outcome of CRN which was identified if any of the following types of
      CRN were reported: 1) skipped medication doses to save money, 2) took less
      medication to save money, and 3) delayed prescription filling to save money.
      RESULTS: Among CVD patients who had used a prescription medication in the last 12
      months, 10.0% skipped medication doses, 10.6% took less medication, and 12.8%
      delayed filling their prescriptions. After adjusting for confounding factors,
      gender was found to be significantly associated with the composite outcome of CRN
      among CVD patients. Women were 1.54 times (95% confidence interval, 1.33-1.77)
      more likely to have any of the types of CRN compared with men. CONCLUSION: There
      are significant gender disparities in CRN among CVD patients. More support for
      and closer monitoring of CRN is needed for disadvantaged groups, especially women
      with limited resources.

PMID- 27894673
TI  - Treatment-related Death in Cancer Patients Treated with Immune Checkpoint
      Inhibitors: A Systematic Review and Meta-analysis.
AB  - AIMS: We carried out a meta-analysis to determine the risk of treatment-related
      death associated with immune checkpoint inhibitor use in cancer patients.
      MATERIALS AND METHODS: We examined data from the Medline and Google Scholar
      databases. We also examined original studies and review articles for cross
      references. Eligible studies included randomised phase II and phase III trials of
      patients with cancer treated with ipilimumab, pembrolizumab; nivolumab;
      tremelimumab and atezolizumab. The authors extracted relevant information on
      participants, characteristics, treatment-related death and information on the
      methodology of the studies. RESULTS: After exclusion of ineligible records, 18
      clinical trials were included in the analysis. The odds ratio for treatment
      related death for CTLA-4 inhibitors (ipilimumab and tremelimumab) was 1.80 (95%
      confidence interval 1.25, 2.59; P=0.002) and for PD-1/PD-L1 inhibitors
      (nivolumab, pembrolizumab and atezolizumab) was 0.63 (95% confidence interval
      0.31, 1.30; P=0.22). Treated cancer seems to have no effect on the risk of
      treatment-related death. CONCLUSIONS: Analysis of our data showed that CTLA-4
      inhibitors (ipilimumab and tremelimumab) in a higher dose (10 mg/kg) seem to be
      associated with a higher risk of treatment-related death compared with control
      regimens, whereas PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab and
      atezolizumab) do not cause the same risk. Clinicians have to be fully aware of
      these differential risks and council their patients appropriately.

PMID- 27894672
TI  - microRNA-145 regulates the RLR signaling pathway in miiuy croaker after poly(I:C)
      stimulation via targeting MDA5.
AB  - MicroRNAs (miRNAs) are endogenous small non-coding RNAs that participate in
      diverse biological processes via degrading the target mRNAs or repressing
      translation. In this study, the regulation of miRNA to the RLR (RIG-I-like
      receptor) signaling pathway by degrading the target mRNAs was researched in miiuy
      croaker. MDA5, a microRNA-145-5p (miR-145-5p) putative target gene, was predicted
      by bioinformatics, and the target sites from the 3'untranslated region of MDA5
      transcripts were confirmed using luciferase reporter assays. Pre-miR-145 was more
      effective in inhibiting MDA5 than miR-145-5p mimic, and the effect was dose- and
      time-dependent. The expression patterns of miR-145-5p and MDA5 were analyzed in
      liver and kidney from miiuy croaker. Results implied that miR-145-5p may function
      via degrading the MDA5 mRNAs, thereby regulating the RLR signaling pathway.
      Studies on miR-145-5p will enrich knowledge of its functions in immune response
      regulation in fish, as well as offer a basis for regulatory networks that are
      composed of numerous miRNAs.

PMID- 27894674
TI  - Emergence of plasmid-mediated colistin resistance and New Delhi metallo-beta
      lactamase genes in extensively drug-resistant Escherichia coli isolated from a
      patient in Thailand.
AB  - We reported a case of Escherichia coli with colistin resistance and an
      extensively drug-resistant phenotype. Molecular analysis revealed that the
      isolate carried mcr-1 and multiple beta-lactamase genes includingblaNDM1, blaCTX
      M-15, blaTEM1, and blaCMY-2. This is the first report of a clinical mcr-1 isolate
      in Thailand highlighting the urgent need for a comprehensive antimicrobial
      resistance containment strategy to prevent further spread.

PMID- 27894675
TI  - The manifestation of vortical and secondary flow in the cerebral venous outflow
      tract: An in vivo MR velocimetry study.
AB  - Aberrations in flow in the cerebral venous outflow tract (CVOT) have been
      implicated as the cause of several pathologic conditions including idiopathic
      intracranial hypertension (IIH), multiple sclerosis (MS), and pulsatile tinnitus
      (PT). The advent of 4D flow magnetic resonance imaging (4D-flow MRI) has recently
      allowed researchers to evaluate blood flow patterns in the arterial structures
      with great success. We utilized similar imaging techniques and found several
      distinct flow characteristics in the CVOT of subjects with and without lumenal
      irregularities. We present the flow patterns of 8 out of 38 subjects who have
      varying heights of the internal jugular bulb and varying lumenal irregularities
      including stenosis and diverticulum. In the internal jugular vein (IJV) with an
      elevated jugular bulb (JB), 4Dflow MRI revealed a characteristic spiral flow that
      was dependent on the level of JB elevation. Vortical flow was also observed in
      the diverticula of the venous sinuses and IJV. The diversity of flow complexity
      in the CVOT illustrates the potential importance of hemodynamic investigations in
      elucidating venous pathologies.

PMID- 27894676
TI  - A multiscale biomechanical model of platelets: Correlating with in-vitro results.
AB  - Using dissipative particle dynamics (DPD) combined with coarse grained molecular
      dynamics (CGMD) approaches, we developed a multiscale deformable platelet model
      to accurately describe the molecular-scale intra-platelet constituents and
      biomechanical properties of platelets in blood flow. Our model includes the
      platelet bilayer membrane, cytoplasm and an elaborate elastic cytoskeleton.
      Correlating numerical simulations with published in-vitro experiments, we
      validated the biorheology of the cytoplasm, the elastic response of membrane to
      external stresses, and the stiffness of the cytoskeleton actin filaments,
      resulting in an accurate representation of the molecular-level biomechanical
      microstructures of platelets. This enabled us to study the mechanotransduction
      process of the hemodynamic stresses acting onto the platelet membrane and
      transmitted to these intracellular constituents. The platelets constituents
      continuously deform in response to the flow induced stresses. To the best of our
      knowledge, this is the first molecular-scale platelet model that can be used to
      accurately predict platelets activation mechanism leading to thrombus formation
      in prosthetic cardiovascular devices and in vascular disease processes. This
      model can be further employed to study the effects of novel therapeutic
      approaches of modulating platelet properties to enhance their shear resistance
      via mechanotransduction pathways.

PMID- 27894677
TI  - Factors affecting the results of the functional dexterity test.
AB  - STUDY DESIGN: Cross-sectional study. PURPOSE OF THE STUDY: The purpose of this
      study was to identify which demographic and anthropometric features affect
      performance (time) on the functional dexterity test (FDT). METHODS: One hundred
      fifty-two healthy subjects between the ages of 20 and 80 years were included in
      this cross-sectional study. Demographic characteristics (age, gender, height,
      weight, and dominant hand) and anthropometric (the girths of the first 3 fingers)
      variables were recorded, and the FDT (net time and total score) was performed.
      RESULTS: Hand dexterity (time) was slower in participants aged 60 years (35.7 +/-
      9.4 seconds) and older compared with those aged 40-59 (27.1 +/- 7.2 seconds)
      years and 20-39 (23.9 +/- 4.9 seconds) years (P < .001 for both) in dominant
      side. DISCUSSION: There was no significant difference between males (29.1 +/- 9
      in dominant hands and 30.9 +/- 9.5 in nondominant hands) and females (27.9 +/-
      8.4 in dominant hands and 30.8 +/- 8.1 in nondominant hands) in all groups in
      terms of FDT net time. The factors associated with hand dexterity were age in
      dominant hands (R2 = 0.321) and age and thickness of the second and third fingers
      in nondominant hands (R2 = 0.282). CONCLUSION: FDT scores increased with
      increasing age for both dominant and nondominant hands. Finger thickness,
      especially in nondominant hands, should be taken into account while evaluating
      FDT scores because of its negative effect on dexterity. LEVEL OF EVIDENCE: Level
      2.

PMID- 27894678
TI  - A simple orthosis solves a problem in a patient with a dystonic finger after
      stroke.
AB  - These authors use a custom-fabricated orthotic device to improve hand motion and
      function for a client with hand dystonia after stroke. Clinical observation and
      reasoning resulted in an effective solution to control the dystonia that was
      acceptable to the client. - Kristin Valdes, OTD, OT, CHT, Practice Forum Editor.

PMID- 27894679
TI  - Use of the lymphocyte cytokinesis-block micronucleus assay in occupational
      biomonitoring of genome damage caused by in vivo exposure to chemical genotoxins:
      Past, present and future.
AB  - This article concerns the use of the lymphocyte cytokinesis-block micronucleus
      (CBMN) assay in biomonitoring of occupational and environmental exposures to
      genotoxic agents. Furthermore, we evaluated the use of this method in different
      exposure scenarios, in comparison to other DNA damage biomarkers and its regional
      distribution. So far ca. 400 studies have been published and the number increased
      substantially in the last years. The most frequently investigated groups are
      hospital personnel, followed by workers in the chemical industry and agricultural
      workers. The lymphocyte CBMN assay is more frequently used in occupational
      studies than MN assays with epithelial cells and other methods, such as
      chromosomal aberration analyses, Comet assay and DNA-adduct measurements. The use
      of probes which enable the discrimination between MN containing chromosome
      fragments and whole chromosomes allows the identification of the molecular
      mechanisms of MN formation. Most studies were performed in Europe and Asia (ca.
      65% and 25%, respectively). Important future developments will be the evaluation
      of the biological consequences of formation of additional nuclear endpoints (e.g.
      nucleoplasmic bridges), the improvement of the understanding of the health
      consequences of their formation, and the use of automated scoring devices. Future
      applications of the CBMN assay should address new emerging problems, e.g. the
      potential genotoxic damage induced by the use of nanoparticles and mobile phones.
      The control of occupational exposures to chemical genotoxins is currently based
      on chemical measurements which do not reflect interactions of individual factors
      and the inclusion of the lymphocyte CBMN assay in routine surveillance of workers
      could contribute substantially to the prevention of adverse health effects.

PMID- 27894680
TI  - Frequency of micronuclei and other biomarkers of DNA damage in populations
      exposed to dusts, asbestos and other fibers. A systematic review.
AB  - Airborne particles are small, solid particles projected into the air either by
      natural forces, or by mechanical or man-made processes, and include fibers and
      dusts. Their toxicity is usually subsequent to inhalation and can lead to
      pulmonary dysfunctions and diseases, including cancer. Cytochalasin B blocked
      micronucleus assay in lymphocytes (L-CBMN) has been shown as a sensitive and
      reliable technique in assessing genotoxic exposure, An extensive search of the
      PubMed and Web of Science databases allowed retrieval of 18 articles on
      occupational or environmental exposure evaluating L-CBMN in subjects exposed to
      fibers or dusts (asbestos, silica, rockwool, beryllium, tobacco, and wood). For
      each study, mean L-CBMN levels were compared in exposed subjects vs. unexposed
      controls providing a point estimate, the Mean Ratio (MR). The high heterogeneity
      among retrieved studies and their relatively limited number did not allow a
      quantitative meta-analysis. However, the inter-quartile range of all MRs fell
      within the interval between 1.25 and 2.23, supporting the hypothesis that
      exposure to airborne particles increases DNA damage, although mechanisms of
      genotoxicity should be further investigated. A borderline significant correlation
      was found with SCE, but not with chromosome aberrations or comet assay. Future
      research should focus on exposure assessment, in order to perform proper dose
      response studies and disentangle the effect of different compounds in mixed
      exposures. To fully exploit the cytome assay, L-CBMN frequency should be
      integrated with other endpoints, such as nucleoplasmic bridges and nuclear buds.
      The use of alternative tissues, such as nasal and buccal mucosa, and the
      implementation of other cytogenetic assay, may help to understand the effects of
      this exposure.

PMID- 27894681
TI  - Results of micronucleus assays with individuals who are occupationally and
      environmentally exposed to mercury, lead and cadmium.
AB  - Millions of humans are exposed occupationally and environmentally to lead,
      mercury and cadmium compounds. Mercury compounds are less abundant but some of
      them belong to the most toxic chemicals which are known. We evaluated the
      literature to find out if these metals act in humans as genotoxic carcinogens and
      if their health effects can be predicted by use of micronucleus (MN) assays with
      lymphocytes and/or with other genotoxicity tests. Numerous studies showed that
      lead and mercury induce cancer in humans and also in animals, in vitro
      experiments with cultured cells indicate that they cause DNA damage via different
      molecular mechanisms including release of reactive oxygen species and
      interactions with DNA repair processes. Also in most human studies, positive
      results were obtained in MN tests with lymphocytes (all 15 occupational studies
      with lead yielded positive results, with mercury 6 out of 7 investigations were
      positive). For cadmium, there is clear evidence that it causes cancer in humans;
      however, induction of chromosomal damage was only seen in high dose experiments
      with mammalian cells while results of animal and human studies yielded
      conflicting results (only in 2 of 5MN trials with humans positive findings were
      reported). Possibly, non-genotoxic mechanisms such as inhibition of apoptosis and
      interaction with signaling pathways account for the carcinogenic properties of
      cadmium species. The findings of MN studies with lead and mercury are in
      excellent agreement with results which were obtained with other endpoints (e.g.
      chromosomal aberrations and comet formations) and it is evident that this
      approach can be used for occupational and environmental monitoring of exposed
      individuals. Important future tasks will be the realization of larger studies
      with a uniform standardized protocol, the additional evaluation of anomalies
      other than MN (nuclear buds and bridges) and the combination of such trials with
      investigations which allow to define the molecular mechanisms relevant for
      exposed humans.

PMID- 27894682
TI  - Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic
      agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in
      humans.
AB  - The purpose of this review is to summarise current knowledge on the molecular
      mechanisms by which in vivo exposure to exogenous chemical genotoxins in humans
      induces micronuclei (MNi) and other nuclear anomalies in lymphocytes in vivo and
      ex vivo after nuclear division in vitro. MNi originate from acentric chromosome
      fragments and/or whole chromosomes that are unable to engage with the mitotic
      spindle and/or fail to segregate properly to the daughter nuclei during anaphase.
      The lagging fragments or whole chromosomes are surrounded by membrane and become
      MNi. Acentric fragments are caused by failure of repair or mis-repair of DNA
      strand breaks which may be induced by chemicals that (i) damage the
      phosphodiester backbone of DNA, and/or (ii) inhibit the DNA damage response
      mechanisms or repair of DNA strand breaks and/or (iii) cause DNA replication
      stress due to DNA adduct or cross-link formation. MNi originating from lagging
      whole chromosomes may be induced by chemicals that cause defects in centromeres
      or the mitotic machinery. Mis-repair of chemically-induced DNA breaks may also
      cause formation of dicentric chromosomes and nucleoplasmic bridges (NPBs) between
      daughter nuclei in mitosis. NPBs may break and initiate recurring breakage-fusion
      bridge cycles and chromosomal instability. The review also explores knowledge on
      (i) the routes by which lymphocytes in the human body may be exposed to genotoxic
      chemicals, (ii) kinetics of MNi expression in lymphocytes in vivo and ex vivo in
      the lymphocyte cytokinesis-block micronucleus (L-CBMN) assay and (iii) current
      evidence on the efficiency of the L-CBMN assay in detecting in vivo exposure to
      chemical genotoxins and its concordance with MNi expression in epithelial
      tissues. The review also identifies important knowledge gaps (e.g. effect of
      nanomaterials; interactions with nutritional deficiencies etc.) regarding
      mechanisms by which in vivo chemical genotoxin exposure may cause MNi formation
      in lymphocytes in vivo and ex vivo in lymphocytes.

PMID- 27894683
TI  - Biomonitoring of humans exposed to arsenic, chromium, nickel, vanadium, and
      complex mixtures of metals by using the micronucleus test in lymphocytes.
AB  - Various metals have demonstrated genotoxic and carcinogenic potential via
      different mechanisms. Until now, biomonitoring and epidemiological studies have
      been carried out to assess the genotoxic risk to exposed human populations. In
      this sense, the use of the micronucleus assay in peripheral blood lymphocytes has
      proven to be a useful tool to determine increased levels of DNA damage, as a
      surrogate biomarker of cancer risk. Here we review those biomonitoring studies
      focused on people exposed to arsenic, chromium, nickel, vanadium and complex
      mixtures of metals. Only those studies that used the frequency of micronuclei in
      binucleated (BNMN) cells have been taken into consideration, although the
      inclusion of other biomarkers of exposure and genotoxicity are also reflected and
      discussed. Regarding arsenic, most of the occupational and environmental
      biomonitoring studies find an increase in BNMN among the exposed individuals.
      Thus, it seems conclusive that arsenic exposure increases the risk of exposed
      human populations. However, a lack of correlation between the level of exposure
      and the increase in BNMN is also common, and a limited number of studies
      evaluated the genotype as a risk modulator. As for chromium, a BNMN increase in
      occupationally exposed subjects and a correlation between level of exposure and
      effect is found consistently in the available literature. However, the quality
      score of the studies is only medium-low. On the other hand, the studies
      evaluating nickel and vanadium are scarce and lacks a correct characterization of
      the individual exposure, which difficult the building of clear conclusions.
      Finally, several studies with medium-high quality scores evaluated a more
      realistic scenario of exposure which takes into account a mixture of metals.
      Among them, those which correctly characterized and measured the exposure were
      able to find association with the level of BNMN. Also, several genes associated
      with DNA damage repair such as OGG1 and XRCC1 were found to influence the
      exposure effect.

PMID- 27894684
TI  - Systematic review of the use of the lymphocyte cytokinesis-block micronucleus
      assay to measure DNA damage induced by exposure to polycyclic aromatic
      hydrocarbons.
AB  - The effect of exposure to polycyclic aromatic hydrocarbons (PAHs) to induce
      micronuclei (MN) measured using the lymphocytes cytokinesis-block micronucleus
      (CBMN) assay were evaluated in 34 studies according to the exposure: 20 studies
      in coke oven workers, 7 studies in different occupational exposures as alluminium
      industry workers, rubber factory workers, road construction workers, airport
      workers and diesel exposed workers, 6 studies on environmentaly exposed groups as
      police, volunteers and children. Reviewed papers indicate that the CBMN assay is
      a sensitive biomarker of PAHs exposure in polluted air. Reviewed studies
      confirmed previous conclusions, that the frequency of MN measured using the
      lymphocyte CBMN is not significantly affected by smoking, females are more
      sensitive to PAHs than males, the frequency of MN is increased with age.

PMID- 27894685
TI  - DNA damage induced by occupational and environmental exposure to miscellaneous
      chemicals.
AB  - Epidemiological studies for hazardous situations resulting from the risk of
      environmental and/or occupational exposure to miscellaneous chemicals present
      several difficulties. Biomonitoring of human populations can provide an early
      detection system for the initiation of cell dysregulation in the development of
      cancer, which would help develop an efficient prevention program. Recently, the
      cytokinesis-block micronucleus (CBMN) assay in lymphocyte cells has become an
      important tool for assessing DNA damage in exposed populations. This is the
      method of choice for population-based studies of occupational and/or
      environmental exposure to different agents. In this review, human populations
      exposed to coal, dyes, paints, organic solvents in a complex mixture, and others
      miscellaneous chemicals were analyzed. Data from 28 studies was evaluated in
      relation to the effect of complex mixture exposition on micronucleus (MN)
      frequency. Other biomarkers and the background factors were evaluated as well,
      such as gender, age, or smoking habit. Most of these studies (75%) showed a
      significant increase of micronucleated cells to exposed groups in relation to the
      control groups, besides chromosomal aberrations (CA), sister chromatid exchanging
      (SCE) and comet cells (comet assay). The studies from this review about
      miscellaneous chemicals exposures using CBMN assay have indicated some time and
      dose-dependent effects. Overall, the findings suggest that the responses
      resulting from exposure to complex mixtures are varied and complicated. However,
      they are also an important mechanism of DNA damage concerning disruption of metal
      ion homeostasis that may lead to oxidative stress, a state where increased
      formation of reactive oxygen species (ROS) overwhelms body antioxidant protection
      and subsequently could induce cancer.

PMID- 27894686
TI  - The use of the lymphocyte cytokinesis-block micronucleus assay for monitoring
      pesticide-exposed populations.
AB  - Pesticides are widely used around the world, and hundreds of millions of people
      are exposed annually in occupational and environmental settings. Numerous studies
      have demonstrated relationships between pesticide exposure and increased risk of
      cancers, neurodegenerative and neurodevelopmental disorders, respiratory diseases
      and diabetes. Assessment of genotoxicity of pesticides and biomonitoring their
      effect in exposed populations is critical for a better regulation and protection,
      but it can be complicated because pesticides are often used as complex mixtures.
      The cytokinesis-block micronucleus assay in human lymphocytes (L-CBMN) is a
      validated method of assessment of DNA damage induced by clastogenic and
      aneuploidogenic mechanisms. The goal of this review is to provide an updated
      summary of publications on biomonitoring studies using this assay in people
      exposed to pesticides in different settings, and to identify gaps in knowledge,
      and future directions. A literature search was conducted through MedLine/PubMed
      and TOXLINE electronic databases up to December 2015. A total of 55 full-text
      articles, related to 49 studies, excluding reviews, were selected for in depth
      analysis, divided by the settings where exposures occurred, such as chemical
      plant workers, pesticide sprayers, floriculturists, agricultural workers and non
      occupationally exposed groups. Majority of studies (36 out of 49) reported
      positive findings with L-CBMN assay. However, most of the studies of professional
      applicators that used single pesticide or few compounds in the framework of
      specific programs did not show significant increases in MN frequency. A decreased
      level of pesticide-induced genotoxicity was associated with the proper use of
      personal protection. In contrast, subjects working in greenhouses or during
      intensive spraying season and having acute exposure, showed consistent increases
      in MN frequency. Overall, this analysis confirmed that L-CBMN is an excellent
      tool for pesticide biomonitoring, and can validate the effects of educational and
      intervention programs on reducing exposure and genetic damage.

PMID- 27894687
TI  - Reprint of "Biomonitoring of genotoxic effects for human exposure to
      nanomaterials: The challenge ahead".
AB  - Exposures to nanomaterials (NMs), with their specific physico-chemical
      characteristics, are likely to increase over the next years, as their production
      for industrial, consumer and medical applications is steadily rising. Therefore,
      there is an urgent need for the implementation of human biomonitoring studies of
      genotoxic effects after NM exposures in order to monitor and assure safety for
      workers and the general population. In this review, most commonly used biomarkers
      of early genetic effects were analyzed for their adequacy after NM exposures. A
      more in depth analysis of the ex vivo/in vitro lymphocyte MN assay was performed,
      although, in literature no studies are available using this assay for NM
      exposures. Therefore, the known factors determining the NMs tissue/cellular
      targets and the multiplicity of modes of action of NMs were summarized. The main
      pending questions are whether (1) lymphocytes are a NM target or an adequate
      surrogate tissue, (2) whether the buccal MN assay might be more suitable for NM
      exposures via inhalation or ingestion, as buccal cells might be exposed more
      directly. While the current state-of-the-art does not allow for drawing firm
      conclusions, major research gaps are identified and some cautious recommendations
      can be formulated. Therefore in vitro and in vivo studies should be conducted
      comparing methodologies side-by-side in the same subjects and for different types
      of NMs. The ex vivo/in vitro MN assay in its automated version, allowing
      objective analysis of large cohorts and detection of direct and indirect
      genotoxic effects, remains a valuable candidate for human biomonitoring to NM
      exposure. Considering the potential cancer risk from exposure to NMs and previous
      dramatic experiences with too late surveillance of occupational exposures to
      similar substances (e.g. to asbestos), there is an urgent need to define and
      implement adequate scientifically sound biomonitoring methods and programme for
      exposure to NMs.

PMID- 27894688
TI  - DNA and chromosomal damage in medical workers exposed to anaesthetic gases
      assessed by the lymphocyte cytokinesis-block micronucleus (CBMN) assay. A
      critical review.
AB  - The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in
      hundreds of in vivo biomonitoring studies of humans exposed either
      environmentally or occupationally to genotoxic chemicals. However, there is an
      emerging need to re-evaluate the use of MN and other biomarkers within the
      lymphocyte CBMN cytome assay as quantitative indicators of exposure to main
      classes of chemical genotoxins. The main aim of the present report is to
      systematically review published studies investigating the use of the lymphocyte
      CBMN assay to determine DNA damage in subjects exposed to anaesthetic gases. We
      also compared performance of the CBMN assay with other DNA damage assays employed
      and identified strengths and weaknesses of the published studies. We have
      retrieved 11 studies, published between 1996 and 2013, reporting MN associated
      with occupational exposures (operating room personnel). The individual job
      categories were often described (anaesthesiologists, technicians, radiologists)
      among cases, as well as duration of exposure. All studies reported the compounds
      present at the workplace and, in some instances, the exposure levels were
      measured. Controls were usually recruited among personnel at the hospital not
      exposed to anaesthetics or they were healthy unexposed subjects from general
      population. The number of investigated subjects, due to the character of the
      occupation, was relatively smaller than those investigated in other occupational
      monitoring settings. Overall, the majority of the studies were age- and gender-
      matched (or investigated only males or females) while less attention was given to
      lifestyle confounders. Appropriate measurement of exposure, available in
      approximately half of the studies only, was compromised by the lack of the
      personal dosimetry-based determinations. In all studies, higher MN frequencies
      were observed in exposed individuals. The meta-analysis of mean MN frequency of
      combined studies confirmed this tendency (log mean ratio=0.56 [0.34-0.77];
      P=3.51*10-7). Similar differences between the exposed and controls were also
      observed for other biomarkers.

PMID- 27894689
TI  - Occupational exposure to cytostatic/antineoplastic drugs and cytogenetic damage
      measured using the lymphocyte cytokinesis-block micronucleus assay: A systematic
      review of the literature and meta-analysis.
AB  - Many studies have reported the occurrence of work-environment contamination by
      antineoplastic drugs (ANPD), with significant incorporation of trace amounts of
      these hazardous drugs in hospital personnel. Given the ability of most ANPD to
      actively bind DNA, thus inducing genotoxic effects, it is of pivotal importance
      to assess the degree of genotoxic damage (i.e., residual genotoxic risk) in
      occupationally exposed subjects. The lymphocyte cytokinesis-block micronucleus (L
      CBMN) assay is largely used for biological effect monitoring in subjects
      occupationally exposed to ANPD. In this study, we identified and analyzed the
      studies published reporting the use of the L-CBMN assay as biomarker of genotoxic
      risk in health care workers exposed to ANPD with the aim of performing meta
      analysis and providing a meta-estimate of the genotoxic effect of exposure. We
      retrieved 24 studies, published from 1988 to 2015, measuring MN in peripheral
      blood lymphocytes in health care workers occupationally exposed to ANPD. In 15
      out of the 24 studies (62.5%), increased MN frequencies were recognized in
      exposed subjects as compared to controls. The meta-analysis of MN frequency of
      the combined studies confirmed an association between occupational exposure to
      ANPD and cytogenetic effects with an overall meta-estimate of 1.67 [95% CI: 1.41
      1.98]. In 16 out of the 24 studies (66.6%) at least one other genotoxicity
      biomarker, besides L-CBMN assay, was employed for biological effect monitoring.
      In several studies the effect of exposure to ANPD was evaluated also in terms of
      MN in exfoliated buccal cells. Other studies focused on genotoxicity endpoints,
      such as sister chromatid exchanges (3 studies), chromosome aberrations (6
      studies), or primary DNA damage investigated by comet assay (7 studies). Overall,
      there was good agreement between other genotoxicity tests employed and L-CBMN
      assay outcomes.

PMID- 27894690
TI  - A systematic review of the association between occupational exposure to
      formaldehyde and effects on chromosomal DNA damage measured using the cytokinesis
      block micronucleus assay in lymphocytes.
AB  - Formaldehyde (FAL) is classified as a Class I carcinogen by the WHO International
      Agency for Research on Cancer. Therefore, there is a need to validate appropriate
      methods for detecting its genotoxic effects in vivo in humans. One of the most
      commonly used methods to measure the genotoxic effects of exposure to
      environmental chemicals is the lymphocyte cytokinesis-block micronucleus (L-CBMN
      assay). We performed a systematic review and statistical analysis of the results
      from all of the published studies in which the L-CBMN assay was used to measure
      the genotoxic effects of human exposure to FAL. The results of this systematic
      review indicated that the majority (62%) of the 21 investigations in the 17
      published studies we examined showed significant increases in lymphocyte
      micronucleus (MN) frequency (a biomarker of chromosome breakage or loss), in
      exposed subjects relative to controls. We used a novel quality score tool to
      determine if the investigations adequately addressed known variables that affect
      MN frequency in lymphocytes and found that MN frequency was not explained by
      quality because there was no significant correlation between quality score and
      fold-change in MN frequency (R=0.008, P=0.97). The results of all of the studies
      (positive or negative), when combined together, indicated a highly significant
      doubling in lymphocyte MN frequency in those exposed to FAL relative to controls
      (P<0.0001). These observations, together with a significant positive correlation
      between L-CBMN assay MN frequency and FAL air concentration (R=0.529, P=0.017)
      indicate the suitability of this method to measure in vivo genotoxicity of FAL.
      Furthermore, fold-increase in lymphocyte MN frequency in the exposed subjects
      relative to controls was strongly positively correlated with the duration of FAL
      exposure (R=0.779, P<0.0001) suggesting the need to better understand the
      potential for cumulative genomic instability induced by chronic exposures to FAL.

PMID- 27894691
TI  - Application of the lymphocyte Cytokinesis-Block Micronucleus Assay to populations
      exposed to petroleum and its derivatives: Results from a systematic review and
      meta-analysis.
AB  - The lymphocyte cytokinesis-block micronucleus (CBMN) assay is applied in many
      different in vivo biomonitoring studies of human exposure to genotoxic chemicals.
      Among extensively chemicals investigated, we identified petroleum and its
      derivatives, in particular benzene and the most common mixture of benzene,
      toluene, and xylene. Although conflicting results have been reported on the
      effects of benzene exposure, the number of positive findings in independent
      studies suggests that occupational exposure to benzene causes DNA damage in
      peripheral blood lymphocytes. To assess current evidence on this hypothesis, we
      conducted a meta-analysis. Our aim was to evaluate the effect of benzene exposure
      on genetic damage, quantified using the CBMN assay on individuals occupationally
      exposed to petroleum and its derivatives. Statistical analyses were conducted
      using the rmeta package from the free Software Environment for Statistical
      Computing R. Combined study results indicated that benzene exposure is associated
      with an increased level of genetic damage in peripheral blood lymphocytes, as
      reflected by an increased MN frequency. The summary mean difference in MN
      frequency between exposed and unexposed individuals was 1.64 (95% CI: 0.80-2.47).
      Overall, this finding points to MN frequency as a sensitive biomarker which could
      be used to evaluate genetic damage induced by occupational - industrial or
      environmental - exposure to benzene. This review also identified some important
      knowledge gaps as well as the need of large, well-designed studies. In
      particular, it is fundamental to accurately characterize the investigated
      population, including dietary habits and genetic variability which could modulate
      MN frequency in both exposed individuals and unexposed controls. In conclusion,
      according to present findings the use of the CBMN assay in biomonitoring studies
      could provide objective evidence to guide prioritization of preventive
      interventions in subjects occupationally exposed to petroleum derivatives, and in
      particular benzene.

PMID- 27894693
TI  - Genotoxicity of ethylene oxide: A review of micronucleus assay results in human
      population.
AB  - Ethylene oxide (EtO) has been categorized as "carcinogenic to humans (Group 1)"
      by the IARC. While several epidemiological studies have reported carcinogenicity
      and EtO-Hb formation; information from cytogenetic endpoints are rather
      inconclusive. In the present review, we focus on the results of eleven studies
      which have reported the results of micronucleus assay in EtO exposed workers. We
      have critically reviewed these studies based on the exposure assessment,
      concentration and duration, and compared the sensitivity of micronucleus assay to
      other reported endpoints like EtO-Hb, CA, SCE. The levels of EtO and EtO-Hb
      adducts in all the studies were strongly correlated to the results of SCE, but
      not to MN. MN were only observed in a limited number of studies with high EtO
      exposure (2-28ppm 8h-TWA) and not below the recommended concentration of <1ppm.
      To further understand the effect of exposure of EtO on MN assay outcome, we
      propose studies with more harmonized protocol for exposure assessment and MN
      analysis, determination of suitable sample size and use of multiple target
      tissues to understand the effect of metabolite.

PMID- 27894692
TI  - The ex vivo L-CBMN assay detects significant human exposure to butadiene.
AB  - 1,3-Butadiene (BD), an important industrial chemical used in the production of
      synthetic rubber and resins and a ubiquitous environmental pollutant, was
      classified as a human carcinogen by IARC. BD requires metabolic activation to
      different epoxides that are known to bind to DNA, inducing also DNA-DNA and DNA
      protein crosslinks. The DNA damage leading to mutations has been identified as
      the mode of action of BD. Experimental studies in rodents revealed widely
      different BD carcinogenic/mutagenic potency in rat and mice, associated to
      differences in BD metabolism. The available biomonitoring studies in workers
      occupationally exposed to BD, considering different genetic endpoints, do not
      allow to reach a conclusion on the BD carcinogenic/mutagenic risk in humans. The
      present systematic review retrieves and analyzes the published studies on the
      application of the cytokinesis-block micronucleus assay in peripheral lymphocytes
      (L-CBMN) of BD exposed subjects. Ten articles were retrieved related to seven
      studies on BD exposure and one study on exposure to a mixture of compounds in a
      styrene-butadiene tire manufacturing plant. Four studies carried out in Europe
      related to heterogeneous groups of workers exposed in BD monomer or polymer
      manufacturing and processing industries, reporting mean individual exposure
      levels below 3ppm, failed to find any increase of MN frequency. Three studies,
      including mixed groups of workers involved in different stages of the production
      and manufacturing of BD in China, show increased MN frequencies associated with
      the intensity of the exposure, with a relevant positive response (FR=2.29) when
      the mean cumulative dose was estimated as 266ppm/year. These results are
      consistent with the data on the exposure-response curve for total leukemia
      mortality showing no increase for cumulative exposure less than or equal to 200
      BD ppm-years. The L-CBMN assay, measuring both chromosome breakage and chromosome
      loss, events involved in induction of leukemia, seems to be a promising biomarker
      for cancer risk induced by BD.

PMID- 27894694
TI  - The cytokinesis-block micronucleus (CBMN) assay in human populations exposed to
      styrene: A systematic review and meta-analysis.
AB  - Styrene is a building-block of several compounds used in a wide array of
      materials and products. The most important human exposure to this substance
      occurs in industrial settings, especially among reinforced-plastics industry
      workers. The effect of occupational exposure to styrene on cytogenetics
      biomarkers has been previously reviewed with positive association observed for
      chromosomal aberrations, and inconclusive data for the micronucleus assay. Some
      limitations were noted in those studies, including inadequate exposure assessment
      and poor epidemiological design. Furthermore, in earlier studies micronuclei
      frequency was measured with protocols not as reliable as cytokinesis-block
      micronucleus (CBMN) assay. Aim of the present systematic review and meta-analysis
      is to investigate genomic instability and DNA damage as measured by the CBMN
      assay in lymphocytes of subjects exposed to styrene. A total of 11 studies
      published between 2004 and 2012 were included in the meta-analysis encompassing
      479 styrene-exposed workers and 510 controls. The quality of each study was
      estimated by a quality scoring system which ranked studies according to the
      consideration of major confounders, exposure characterization, and technical
      parameters. An overall increase of micronuclei frequencies was found in styrene
      exposure workers when compared to referents (meta-MR 1.34; 95% CI 1.18-1.52),
      with significant increases achieved in six individual studies. The consistency of
      results in individual studies, the independence of this result from major
      confounding factors and from the quality of the study strengthens the reliability
      of risk estimates and supports the use of the CBMN assay in monitoring genetic
      risk in styrene workers.

PMID- 27894695
TI  - The performance of atmospheric pressure gas chromatography-tandem mass
      spectrometry compared to gas chromatography-high resolution mass spectrometry for
      the analysis of polychlorinated dioxins and polychlorinated biphenyls in food and
      feed samples.
AB  - Recently, gas chromatography tandem mass spectrometry (GC-MS/MS) has been added
      in European Union (EU) legislation as an alternative to magnetic sector high
      resolution mass spectrometry (HRMS) for the analysis of dioxins and dioxin like
      polychlorinated biphenyls (dl-PCB) in food and feed. In this study the
      performance of APGC-MS/MS compared to GC-HRMS is investigated and compared with
      EU legislation. The study includes the legislative parameters, relative
      intermediate precision standard deviation (SRw,rel), trueness, sensitivity,
      linear range and ion ratio tolerance. In addition, over 200 real samples of large
      variety and spanning several orders of magnitude in concentration were analyzed
      by both techniques and the selectivity was evaluated by comparing chromatograms.
      The SRw,rel and trueness were evaluated using (in-house) reference samples and
      fulfill to EU legislation, though the SRw,rel was better with GC-HRMS. The
      sensitivity was considerably better than of GC-HRMS while the linear range was
      similar. Ion ratios were mostly within the tolerable range of +/-15%. A
      (temporary unresolved) systematic deviation in ion ratio was observed for several
      congeners, yet this did not lead to exceeding of the maximum ion ratio limits.
      The APGC-MS/MS results for the non-dioxin-like-PCBs (ndl-PCBs) were negatively
      biased, particularly for PCB138 and 153 in contaminated samples. The selectivity
      of APGC-MS/MS was lower for several matrices. Particularly for contaminated
      samples, interfering peaks were observed in the APGC chromatograms of the native
      compounds (dioxins) and labeled internal standards (PCBs). These can lead to
      biased results and ultimately to false positive samples. It was concluded that
      the determination of dioxins and PCBs using APGC-MS/MS meets the requirements set
      by the European Commission. However, due to generally better selectivity and
      SRw,rel, GC-HRMS is the preferred method for monitoring purposes.

PMID- 27894696
TI  - Complex analysis of concentrated antibody-gold nanoparticle conjugates' mixtures
      using asymmetric flow field-flow fractionation.
AB  - Conjugates of gold nanoparticles (GNPs) with antibodies are powerful analytical
      tools. It is crucial to know the conjugates' state in both the concentrated and
      mixed solutions used in analytical systems. Herein, we have applied asymmetrical
      flow field-flow fractionation (AF4) to identify the conjugates' state. The
      influence of a conjugate's composition and concentration on aggregation was
      studied in a true analytical solution (a concentrated mixture with stabilizing
      components). GNPs with an average diameter of 15.3+/-1.2nm were conjugated by
      adsorption with eight antibodies of different specificities. We found that, while
      the GNPs have a zeta potential of -31.6mV, the conjugates have zeta potentials
      ranging from -5.8 to -11.2mV. Increased concentrations (up to 184nM, OD520=80) of
      the mixed conjugate (mixture of eight conjugates) did not change the form of
      fractograms, and the peak areas' dependence on concentration was strongly linear
      (R2 values of 0.99919 and 0.99845 for absorption signal and light scattering,
      respectively). Based on the gyration (Rg) and hydrodynamic (Rh) radii measured
      during fractionation, we found that the nanoparticles were divided into two
      populations: (1) those with constant radii (Rg=9.9+/-0.9nm; Rh=14.3+/-0.5nm); and
      (2) those with increased radii from 9.9 to 24.4nm for Rg and from 14.3 to 28.1nm
      for Rh. These results confirm that the aggregate state of the concentrated and
      mixed conjugates' preparations is the same as that of diluted preparations and
      that AF4 efficiently characterizes the conjugates' state in a true analytical
      solution.

PMID- 27894697
TI  - An innovative ultrasound assisted extraction micro-scale cell combined with gas
      chromatography/mass spectrometry in negative chemical ionization to determine
      persistent organic pollutants in air particulate matter.
AB  - New clean technologies are needed to determine concentration of organic
      pollutants without generating more pollution. A method to extract Persistent
      Organic Pollutants (POPs) from airborne particulate matter was developed using a
      novel technology recently patented called ultrasound assisted extraction micro
      scale cell (UAE-MSC). This technology extracts, filters, collects the sample, and
      evaporates the solvent, on-line. No sample transfer is needed. The cell minimizes
      sample manipulation, solvent consumption, waste generation, time, and energy;
      fulfilling most of the analytical green chemistry protocol. The methodology was
      optimized applying a centred 23 factorial experimental design. Optimum conditions
      were used to validate and determine concentration of 16 organochlorine pesticides
      (OCls) and 6 polybrominated diphenyl ethers (PBDEs). The best conditions achieved
      were 2 extractions with 5mL (each) of dichloromethane over 5min (each) at 60
      degrees C and 80% ultrasound potency. POPs were determined by gas
      chromatography/mass spectrometry in negative chemical ionization (GC/MS-NCI).
      Analytical method validation was carried out on airborne particles spiked with
      POPs at seven concentration levels between 0.5 and 26.9pgm-3. This procedure was
      done by triplicate (N=21). Recovery, ranged between 65.5+/-2.3% and 107.5+/-3.0%
      for OCls and between 79.1+/-6.5% and 105.2+/-3.8% for PBDEs. Linearity (r2) was
      >=0.94 for all compounds. Method detection limits, ranged from 0.5 to 2.7pgm-3,
      while limits of quantification (LOQ), ranged from 1.7 to 9.0pgm-3. A Bias from 
      18.6% to 9% for PBDEs was observed in the Standard Reference Material (SRM) 2787.
      SRM 2787 did not contain OCls. OCls recoveries were equivalent by UAE-MSC and
      Soxhlet methods UAE-MSC optimized extraction conditions reduced 30 times less
      solvent and decreased the extraction time from several hours to ten minutes,
      respect to Soxhlet. UAE-MSC was applied to 15 samples of particles less than
      2.5MUm (PM2.5) from three seasons (warm dry, rainy, and cold dry) collected in
      five sites around Mexico City. OCls (4,4'-DDE and endrin aldehyde) concentrations
      ranged from <LOQ to 12.6pgm-3, while PBDEs levels were below the quantification
      limit, although BDE-99 was detected in all samples. UAE-MSC is a novel technology
      to determine organic compounds present in trace concentrations in particulate
      matter. This technology can be extended to extract organic compounds in different
      solid matrices to minimize time extraction and solvent consumption.

PMID- 27894698
TI  - Dual effects of eugenol on the neuronal excitability: An in vitro study.
AB  - Besides its well-known actions on sensory afferents, eugenol also affects general
      excitability of the nervous system, but the mechanisms involved in the recent
      effect, especially through modulation of ion channels, have received much less
      attention. In this study, we studied the effects of eugenol on the excitability
      of central neurons of land snail Caucasotachea atrolabiata and tried to elucidate
      the underlying ionic mechanisms. The lower concentration of eugenol (0.5mM)
      reversibly reduced the frequency of spontaneous action potentials that was
      associated with elevation of threshold, reduction of maximum slope of rising
      phase and prolongation of actin potentials. These effects were mimicked by
      riluzole, suggesting that they might be mediated by inhibition of Na+ channels.
      Eugenol also prolonged the single-spike afterhyperpolarization and post stimulus
      inhibitory period, but these effects seemed to be consequent to action potential
      prolongation that indirectly augment Ca2+ inward currents and Ca2+-activated K+
      currents. This concentration of eugenol was also able to prevent or abolish
      pentylenetetrazole-induced epileptiform activity. On the other hand, a higher
      concentration of eugenol (2mM) reversibly increased the frequency of action
      potentials and then induced epileptiform activity in majority of treated neurons.
      Several criteria suggest that the inhibition of K+ channels by higher
      concentration of eugenol and indirect augmentation of Ca2+ currents are central
      to the hyperexcitability and epileptiform activity induced by eugenol. Our
      findings indicate that while low concentration of eugenol could have
      antiepileptic properties, at higher concentration it induces epileptiform
      activity. It seems that does dependent inhibition of the ionic currents
      underlying rising and falling phases of action potential is relevant to the
      eugenol suppressant and excitatory actions, respectively.

PMID- 27894699
TI  - Fault diagnosis for wind turbine planetary ring gear via a meshing resonance
      based filtering algorithm.
AB  - Identifying the differences between the spectra or envelope spectra of a faulty
      signal and a healthy baseline signal is an efficient planetary gearbox local
      fault detection strategy. However, causes other than local faults can also
      generate the characteristic frequency of a ring gear fault; this may further
      affect the detection of a local fault. To address this issue, a new filtering
      algorithm based on the meshing resonance phenomenon is proposed. In detail, the
      raw signal is first decomposed into different frequency bands and levels. Then, a
      new meshing index and an MRgram are constructed to determine which bands belong
      to the meshing resonance frequency band. Furthermore, an optimal filter band is
      selected from this MRgram. Finally, the ring gear fault can be detected according
      to the envelope spectrum of the band-pass filtering result.

PMID- 27894700
TI  - Using the expected detection delay to assess the performance of different
      multivariate statistical process monitoring methods for multiplicative and drift
      faults.
AB  - Using the expected detection delay (EDD) index to measure the performance of
      multivariate statistical process monitoring (MSPM) methods for constant additive
      faults have been recently developed. This paper, based on a statistical
      investigation of the T2- and Q-test statistics, extends the EDD index to the
      multiplicative and drift fault cases. As well, it is used to assess the
      performance of common MSPM methods that adopt these two test statistics. Based on
      how to use the measurement space, these methods can be divided into two groups,
      those which consider the complete measurement space, for example, principal
      component analysis-based methods, and those which only consider some subspace
      that reflects changes in key performance indicators, such as partial least
      squares-based methods. Furthermore, a generic form for them to use T2- and Q-test
      statistics are given. With the extended EDD index, the performance of these
      methods to detect drift and multiplicative faults is assessed using both
      numerical simulations and the Tennessee Eastman process.

PMID- 27894701
TI  - Design of a new PID controller using predictive functional control optimization
      for chamber pressure in a coke furnace.
AB  - An improved proportional-integral-derivative (PID) controller based on predictive
      functional control (PFC) is proposed and tested on the chamber pressure in an
      industrial coke furnace. The proposed design is motivated by the fact that PID
      controllers for industrial processes with time delay may not achieve the desired
      control performance because of the unavoidable model/plant mismatches, while
      model predictive control (MPC) is suitable for such situations. In this paper,
      PID control and PFC algorithm are combined to form a new PID controller that has
      the basic characteristic of PFC algorithm and at the same time, the simple
      structure of traditional PID controller. The proposed controller was tested in
      terms of set-point tracking and disturbance rejection, where the obtained results
      showed that the proposed controller had the better ensemble performance compared
      with traditional PID controllers.

PMID- 27894702
TI  - Adaptive PI controller to voltage regulation in power systems: STATCOM as a case
      study.
AB  - Static synchronous compensator (STATCOM) provides the means to improve quality
      and reliability of a power system as it has the functional capability to handle
      dynamic disturbances, such as transient stability and power oscillation damping
      as well as to providing voltage regulation. In this paper, a robust adaptive PI
      based optimal fuzzy control strategy is proposed to control a STATCOM used in
      distribution systems. The proposed intelligent strategy is based on a combination
      of a new General Type-II Fuzzy Logic (GT2FL) with a simple heuristic algorithm
      named Teaching Learning Based Optimization (TLBO) Algorithm. The proposed
      framework optimally tunes parameters of a Proportional-Integral (PI) controller
      which, similar to most of other researchers regarding control of STATCOM, are in
      charge of controlling the device. The proposed controller guaranties robustness
      and stability against uncertainties caused by external disturbances or ever
      changing nature of the power systems. The TLBO optimizes the parameters of the
      controller as well as the input and output membership functions. To validate the
      efficiency of the proposed controller, the obtained simulation results are
      compared with those of the two most recent researches applied in this field,
      namely, conventional Proportional Integral (PI) controller and Optimal Fuzzy PI
      (OFPI) controller. Results demonstrate the successfulness and effectiveness of
      the proposed online-TLBO General Type-2 Fuzzy PI (OGT2FPI) controller and its
      superiority over conventional approaches.

PMID- 27894703
TI  - Over surgery in breast cancer.
AB  - Breast surgery remains the original and most effective 'targeted' therapy:
      excision of early cancer is curative and for more advanced disease surgery
      improves local disease control. However in well intentioned pursuit of cure and
      local disease control, some cancers are over-treated resulting in major physical
      and emotional morbidity. Less breast surgery is safe, as evidenced by steady
      reductions in mortality and local recurrence; earlier diagnosis and widespread
      use of systemic therapies and radiotherapy have allowed more conservative
      surgery. As tumour biology dictates cancer outcomes not surgery extent, surgery
      can safely be 'minimum required' rather than 'more is better' with the focus on
      removal of disease rather than healthy tissue. Surgeons can reduce the burden of
      surgery further but it is important that less surgery is not over-compensated by
      more radical or unnecessary systemic therapies and/or radiotherapy with their own
      toxicities and morbidity. We all need to be alert to the potential drivers of
      over treatment and over surgery such as failure to work within a
      multidisciplinary team, failure to design a multimodality treatment plan at
      diagnosis or overuse of novel assessment technologies of uncertain clinical
      utility. Pursuit of wide margins and the removal of the contra-lateral healthy
      breast for marginal risk-reduction gains are also to be discouraged as is routine
      local/regional surgery in stage 4 disease. The surgeon has a pivotal role in
      minimizing breast surgery to what is required to achieve the best oncological,
      functional and aesthetic outcomes.

PMID- 27894704
TI  - Antenatal fetal surveillance in multiple pregnancies.
AB  - Multiple pregnancies occur either spontaneously or because of assisted
      reproduction techniques in 1-3% of pregnancies. The presence of more than one
      fetus in the womb is associated with a range of possible complications, both for
      the mother and fetuses. Early detection of these complications followed by timely
      and appropriate management will reduce the risk of adverse outcomes. The
      techniques, skills, and experience for timely detection of complications and
      managing them appropriately require sufficient training and exposure. Therefore,
      referral of women pregnant with more than one fetus to specialized clinics is
      preferable. One of the most essential elements of appropriate management of
      multiple pregnancies is early determination of chorionicity. Monochorionic and
      monoamniotic multiple pregnancies require additional surveillance for a whole
      range of specific complications that are unique to this group. Ultrasound and
      Doppler are the most important tools in the management of multiple pregnancies.
      This chapter will summarize the current best practice, in particular the use of
      ultrasound and Doppler, in the antenatal management of multiple pregnancies.

PMID- 27894705
TI  - Surgical treatment of early-stage ovarian cancer.
AB  - The treatment of early-stage (stages I-IIA) ovarian carcinoma is predominantly
      surgical, and the surgical staging is the most relevant step in the treatment of
      this disease. The significance of surgical staging is twofold. First, proper
      staging distinguishes between 'real' early-stage ovarian carcinoma and 'perhaps'
      early-stage disease. The latter carries an appreciable likelihood of
      unappreciated residual disease in 16-42% of cases. Second, there is solid proof
      that proper surgical staging is an independent prognostic factor for improved
      disease-free and overall survival in early-stage ovarian carcinoma. In this
      chapter, the relevance of various staging steps is discussed and surgical
      guidelines are given. The indication for adjuvant chemotherapy after surgery is
      closely related to the adequacy of surgical staging. Adjuvant chemotherapy only
      works in patients in whom surgical staging was inadequate and who, thus, remain
      with a certain risk of unnoticed residual intraperitoneal or retroperitoneal
      tumour spread. Moreover, there is no indication that adjuvant chemotherapy is of
      any value after an adequate, comprehensive staging procedure. Controversies and
      misunderstandings on this important issue are discussed.

PMID- 27894706
TI  - Improved Radiologists' Efficiency and Accuracy with the Application of Scripting
      Software for the Automated Reporting of Comparison Studies.
AB  - RATIONALE AND OBJECTIVES: The American College of Radiology reporting guidelines
      state that "comparison with relevant examinations and reports should be part of
      the radiologic consultation and report when appropriate and available." MATERIALS
      AND METHODS: We evaluated the use of open-source Windows scripting software for
      the automated retrieval of the date and time of prior studies. RESULTS AND
      CONCLUSION: The date and time of the comparative study are transferred
      automatically to the present report in a structured voice recognition dictation
      system with a "regular expression substitution pattern" construct.

PMID- 27894708
TI  - Comment on: Live tissue versus simulation training for emergency procedures: Is
      simulation ready to replace live tissue?

PMID- 27894709
TI  - External validation in an intermediate unit of a respiratory decompensation model
      trained in an intensive care unit.
AB  - BACKGROUND: Preventing urgent intubation and upgrade in level of care in patients
      with subclinical deterioration could be of great utility in hospitalized
      patients. Early detection should result in decreased mortality, duration of stay,
      and/or resource use. The goal of this study was to externally validate a
      previously developed, vital sign-based, intensive care unit, respiratory
      instability model on a separate population, intermediate care patients. METHODS:
      From May 2014 to May 2016, the model calculated relative risk of adverse events
      every 15 minutes (n = 373,271 observations) for 2,050 patients in a surgical
      intermediate care unit. RESULTS: We identified 167 upgrades and 57 intubations.
      The performance of the model for predicting upgrades within 12 hours was highly
      significant with an area under the curve of 0.693 (95% confidence interval, 0.658
      0.724). The model was well calibrated with relative risks in the highest and
      lowest deciles of 2.99 and 0.45, respectively (a 6.6-fold increase). The model
      was effective at predicting intubation, with a demonstrated area under the curve
      within 12 hours of the event of 0.748 (95% confidence interval, 0.685-0.800). The
      highest and lowest deciles of observed relative risk were 3.91 and 0.39,
      respectively (a 10.1-fold increase). Univariate analysis of vital signs showed
      that transfer upgrades were associated, in order of importance, with rising
      respiration rate, rising heart rate, and falling pulse-oxygen saturation level.
      CONCLUSION: The respiratory instability model developed previously is valid in
      intermediate care patients to predict both urgent intubations and requirements
      for upgrade in level of care to an intensive care unit.

PMID- 27894707
TI  - Missteps in Current Estimates of Cancer Overdiagnosis.
AB  - The balance between the benefits and harms of imaging-based cancer screening
      continues to be an area of controversy and widespread media attention. Of the
      potential harms, overdiagnosis from screening is likely the most elusive in
      estimating and quantifying. This article describes the major methodological
      issues with recently reported estimates of overdiagnosis that are based on excess
      cancer incidence, and suggests that modeling focused on tumor lead-time can serve
      as a complementary method for excess incidence-based overdiagnosis estimates.
      Radiologists should be conversant on the topic of overdiagnosis and understand
      the limitations of different methods used to estimate its magnitude.

PMID- 27894710
TI  - Bowel dysfunction after anastomotic leakage in laparoscopic sphincter-saving
      operative intervention for rectal cancer: A case-matched study in 46 patients
      using the Low Anterior Resection Score.
AB  - BACKGROUND: After sphincter-saving operation for rectal cancer, the impact of
      anastomotic leakage on function has been well studied. The purpose of the present
      work was to assess the influence of symptomatic and asymptomatic anastomotic
      leakage on bowel function and health-related quality of life using the Low
      Anterior Resection Syndrome score and the disease-specific questionnaire European
      Organization for Research and Treatment of Quality of Life Questionnaire for
      Colorectal Cancer. METHODS: The study was a case-matched study with multiple
      controls per case in a variable ratio from a prospectively maintained database
      conducted at a tertiary, colorectal operation referral center. A total of 46
      patients with postoperative anastomotic leakage (symptomatic, n = 23,
      asymptomatic, n = 23) after laparoscopic, sphincter-saving operative intervention
      for rectal cancer were matched with all available patients without anastomotic
      leakage (control group, n = 89) using the following criteria: age, sex, type of
      neoadjuvant treatment, and type of anastomosis. The Low Anterior Resection
      Syndrome score and European Organization for Research and Treatment of Quality of
      Life Questionnaire for Colorectal Cancer were submitted to all included patients.
      The Low Anterior Resection Syndrome scores were categorized into 3 categories (no
      Low Anterior Resection Syndrome, minor Low Anterior Resection Syndrome, and major
      Low Anterior Resection Syndrome). RESULTS: Mean follow-up after stoma closure was
      46 +/- 26 months. Median (interquartile range) Low Anterior Resection Syndrome
      score for all included patients was 27 (16-36). Patients with symptomatic
      anastomotic leakage had impaired Low Anterior Resection Syndrome score: median 30
      (23-39) vs 27 (15-34) in the control group (P = .02), with no Low Anterior
      Resection Syndrome in 4% (vs 31%), minor Low Anterior Resection Syndrome in 52%
      (vs 52%), and major Low Anterior Resection Syndrome in 44% (vs 17%) (P = .004).
      No difference was noted between the asymptomatic anastomotic leakage group and
      control group for median Low Anterior Resection Syndrome score (P = .70) and Low
      Anterior Resection Syndrome categories (no Low Anterior Resection Syndrome, minor
      LARS, and major Low Anterior Resection Syndrome; P = .58). Patients with
      symptomatic anastomotic leakage had significantly more anorectal and urinary
      symptoms compared with patients with no or asymptomatic anastomotic leakage.
      CONCLUSION: Symptomatic anastomotic leakage impairs function and quality of life
      after laparoscopic, sphincter-saving operative intervention for rectal cancer.

PMID- 27894711
TI  - Survival benefit of gastrectomy for gastric cancer in patients >=85 years old: A
      retrospective propensity score-matched analysis.
AB  - BACKGROUND: The purpose of this study was to compare the long-term outcomes of
      patients >=85 years old with gastric cancer who underwent curative distal
      gastrectomy or best supportive care alone. METHODS: Among 241 consecutive
      patients aged >=85 years who were diagnosed with gastric cancer, we
      retrospectively examined the cases of 56 patients that were treated with curative
      distal gastrectomy and 55 patients that were treated with best supportive care
      alone. To reduce selection bias, we conducted a propensity score-matching
      analysis. The patients' propensity scores were estimated using a logistic
      regression model based on the following variables: sex, age, clinical cancer
      stage, performance status score, and each item of the Physiological and Operative
      Severity Score for the enUmeration of Mortality and morbidity score. Overall
      survival was compared using the Kaplan-Meier method and log-rank test. RESULTS:
      Thirty pairs of patients were generated via propensity score matching. The
      clinical characteristics of the 2 groups were well matched. The median overall
      survival time was 57.3 months after distal gastrectomy, while it was 16.0 months
      after best supportive care (P = .0002). Subgroup analyses of each sex showed that
      in males there was no significant difference in overall survival between distal
      gastrectomy and best supportive care (P = .37) while the overall survival of
      females was significantly better after distal gastrectomy than after best
      supportive care (P < .0001). CONCLUSION: Our propensity score-matched study
      suggested that distal gastrectomy results in significantly better long-term
      survival than best supportive care alone in female patients with gastric cancer
      aged >=85 years. In males, the indications for operation should be carefully
      determined.

PMID- 27894712
TI  - Petal, Sepal, or Tepal? B-Genes and Monocot Flowers.
AB  - In petaloid monocots expansion of B-gene expression into whorl 1 of the flower
      results in two whorls of petaloid organs (tepals), as opposed to sepals in whorl
      1 of typical eudicot flowers. Recently, new gene-silencing technologies have
      provided the first functional data to support this, in the genus Tricyrtis
      (Liliaceae).

PMID- 27894713
TI  - Abdominal Aortic Aneurysm in Marfan Syndrome.
AB  - BACKGROUND: Marfan syndrome (MFS) leads to aortic root aneurysm, while descending
      thoracic aortic aneurysm (TAA) occurs less commonly. Abdominal aortic aneurysm
      (AAA) is rarely reported in MFS. Risk factors for AAA are poorly understood and
      there are no guidelines for AAA screening in MFS. We sought to characterize AAA
      among Marfan patients in our center. METHODS: The records of 12 adults with MFS
      and AAA disease were reviewed. Clinical features, imaging, operative reports, and
      outcomes were analyzed. RESULTS: Twelve adults with MFS and AAA were studied; age
      at AAA diagnosis was 44 +/- 15 years (range 18-63). Nine patients smoked
      cigarettes. Eleven patients underwent prior aortic root replacement at age 31 +/-
      15 years. The size of AAA was 5.0 +/- 1.3 cm (range 3.5-7.5) at the time of
      diagnosis. The AAA was suprarenal in 5, juxtarenal in 2, and infrarenal in 5
      patients. Two patients had a descending TAA. Branch vessel aneurysms were present
      in 7 patients. Five patients underwent open surgical repair, 5 underwent
      endovascular repair, and 5 are being treated medically. One patient died suddenly
      with AAA size 5.7 cm, 2 months before death. Three patients subsequently
      developed type B aortic dissection, from 3 months to 9 years after AAA diagnosis.
      CONCLUSIONS: Adults with MFS are at risk for developing AAA. Evaluation for AAA
      is recommended in adults with MFS and prior root replacement, especially if
      descending aortic or branch vessel aneurysm is present or the patient smokes
      cigarettes.

PMID- 27894715
TI  - Refractory complex gastrobroncho-cutaneous fistula after laparoscopic sleeve
      gastrectomy: a novel technique for endoscopic management.

PMID- 27894714
TI  - Conceptualizing and studying binge and loss of control eating in bariatric
      surgery patients-time for a paradigm shift?

PMID- 27894717
TI  - Hepatitis B vaccine alone may be enough for preventing hepatitis B virus
      transmission in neonates of HBsAg (+)/HBeAg (-) mothers.
AB  - BACKGROUND AND AIM: To prospectively evaluate the efficacy of vaccine alone
      compared with vaccine plus HBIG for preventing HBV transmission in neonates of
      HBsAg (+)/HBeAg (-) mothers. METHODS: Combined immunization is currently
      recommended for neonates of HBsAg (+) mothers in China. As a result, a randomized
      design is infeasible due to ethical reasons. In practice, Guangxi Zhuang
      Autonomous Region and Jiangsu Province implement vaccine alone and vaccine plus
      HBIG strategies for neonates born to HBsAg (+)/HBeAg (-) mothers, respectively.
      We alternatively enrolled neonates of HBsAg (+)/HBeAg (-) mothers from these two
      regions. Three doses of a recombinant yeast-derived hepatitis B vaccine were
      given at 0, 1 and 6months with or without HBIG at birth. RESULTS: At 7months,
      sera were collected from 132 neonates in Guangxi Zhuang Autonomous Region and 752
      neonates in Jiangsu Province. Baseline characteristics of both mothers and
      neonates were comparable in the two regions. No differences were revealed
      regarding the occurrence of perinatal HBV transmission with or without HBIG at
      birth [0.1% (1/752) vs. 0.0% (0/132), p=1.000]. The anti-HBs response rates were
      97.7% (129/132) and 98.5% (740/751) for the neonates with vaccine alone and with
      HBIG (p=0.758), respectively. Vaccine alone induced a significantly higher anti
      HBs GMC as compared to vaccine plus HBIG at 7months of age (1555.3mIU/mL vs.
      654.9mIU/mL, p<0.0001). At 12months of age, protective levels of anti-HBs
      remained in 97.4% (596/612) and 98.3% (118/120) of the neonates receiving and not
      receiving HBIG, respectively (p=0.771). The neonates receiving combined
      prophylaxis had a markedly lower anti-HBs GMC (210.7mIU/mL vs. 297.0mIU/mL,
      p=0.011). Horizontal HBV transmission occurred in none of the successfully
      immunized neonates for both compared groups at 12months of age. CONCLUSIONS:
      Vaccine alone may be enough for preventing HBV transmission in neonates of HBsAg
      (+)/HBeAg (-) mothers.

PMID- 27894716
TI  - Characterization of guinea pig T cell responses elicited after EP-assisted
      delivery of DNA vaccines to the skin.
AB  - The skin is an ideal target tissue for vaccine delivery for a number of reasons.
      It is highly accessible, and most importantly, enriched in professional antigen
      presenting cells. Possessing strong similarities to human skin physiology and
      displaying a defined epidermis, the guinea pig is an appropriate model to study
      epidermal delivery of vaccine. However, whilst we have characterized the humoral
      responses in the guinea pig associated with skin vaccine protocols we have yet to
      investigate the T cell responses. In response to this inadequacy, we developed an
      IFN-gamma ELISpot assay to characterize the cellular immune response in the
      peripheral blood of guinea pigs. Using a nucleoprotein (NP) influenza pDNA
      vaccination regimen, we characterized host T cell responses. After delivery of
      the DNA vaccine to the guinea pig epidermis we detected robust and rapid T cell
      responses. The levels of IFN-gamma spot-forming units averaged approximately 5000
      per million cells after two immunizations. These responses were broad in that
      multiple regions across the NP antigen elicited a T cell response. Interestingly,
      we identified a number of NP immunodominant T cell epitopes to be conserved
      across an outbred guinea pig population, a phenomenon which was also observed
      after immunization with a RSV DNA vaccine. We believe this data enhances our
      understanding of the cellular immune response elicited to a vaccine in guinea
      pigs, and globally, will advance the use of this model for vaccine development,
      especially those targeting skin as a delivery site.

PMID- 27894718
TI  - Chlamydia suis and Chlamydia trachomatis induce multifunctional CD4 T cells in
      pigs.
AB  - Chlamydia trachomatis infections are the most prominent bacterial sexually
      transmitted disease world-wide and a lot of effort is put into the development of
      an effective vaccine. Pigs have been shown to be a valuable animal model for C.
      trachomatis vaccine development. The aim of this study was to decipher the T-cell
      mediated immune response to chlamydial infections including C. trachomatis and C.
      suis, the chlamydia species naturally infecting pigs with a demonstrated zoonotic
      potential. Vaginal infection of pigs with C. suis and C. trachomatis lasted from
      3 to 21days and intra-uterine infection was still present after 21days in 3 out
      of 5 C. suis- and 4 out of 5 C. trachomatis-inoculated animals and caused severe
      pathological changes. Humoral immune responses including neutralizing antibodies
      were found predominantly in response to C. suis starting at 14days post
      inoculation. The T-cell-mediated immune responses to C. trachomatis and C. suis
      infections started at 7days post inoculation and consisted mainly of CD4+ T cells
      which were either IFN-gamma single cytokine-producing or IFN-gamma/TNF-alpha
      double cytokine-producing T-helper 1 cells. IL-17-producing CD4+ T cells were
      rare or completely absent. The T-cell-mediated immune responses were triggered by
      both homologous or heterologous re-stimulation indicating that cross-protection
      between the two chlamydia species is possible. Thus, having access to a working
      genital C. suis and C. trachomatis infection model, efficient monitoring of the
      host-pathogen interactions, and being able to accurately assess the responses to
      infection makes the pig an excellent animal model for vaccine development which
      also could bridge the gap to the clinical phase for C. trachomatis vaccine
      research.

PMID- 27894719
TI  - Structural-based designed modular capsomere comprising HA1 for low-cost poultry
      influenza vaccination.
AB  - Highly pathogenic avian influenza (HPAI) viruses cause a severe and lethal
      infection in domestic birds. The increasing number of HPAI outbreaks has
      demonstrated the lack of capabilities to control the rapid spread of avian
      influenza. Poultry vaccination has been shown to not only reduce the virus spread
      in animals but also reduce the virus transmission to humans, preventing potential
      pandemic development. However, existing vaccine technologies cannot respond to a
      new virus outbreak rapidly and at a cost and scale that is commercially viable
      for poultry vaccination. Here, we developed modular capsomere, subunits of virus
      like particle, as a low-cost poultry influenza vaccine. Modified murine
      polyomavirus (MuPyV) VP1 capsomere was used to present structural-based influenza
      Hemagglutinin (HA1) antigen. Six constructs of modular capsomeres presenting
      three truncated versions of HA1 and two constructs of modular capsomeres
      presenting non-modified HA1 have been generated. These modular capsomeres were
      successfully produced in stable forms using Escherichia coli, without the need
      for protein refolding. Based on ELISA, this adjuvanted modular capsomere (CaptHA1
      3C) induced strong antibody response (almost 105endpoint titre) when administered
      into chickens, similar to titres obtained in the group administered with insect
      cell-based HA1 proteins. Chickens that received adjuvanted CaptHA1-3C followed by
      challenge with HPAI virus were fully protected. The results presented here
      indicate that this platform for bacterially-produced modular capsomere could
      potentially translate into a rapid-response and low-cost vaccine manufacturing
      technology suitable for poultry vaccination.

PMID- 27894720
TI  - Polio vaccines: WHO position paper, March 2016-recommendations.
AB  - This article presents the World Health Organization's (WHO) recommendations on
      the use of polio vaccine excerpted from the WHO position paper on polio vaccines 
      March 2016, published in the Weekly Epidemiological Record [1]. This position
      paper on polio vaccines replaces the 2014 WHO position paper [2]. The position
      paper summarizes the WHO position on the introduction of at least one dose of
      inactivated polio vaccine (IPV) into routine immunization schedules as a strategy
      to mitigate the potential risk of re-emergence of type 2 polio following the
      withdrawal of Sabin type 2 strains from oral polio vaccine (OPV) [3]. Footnotes
      to this paper provide a number of core references including references to grading
      tables that assess the quality of the scientific evidence, and to the evidence-to
      recommendation table. In accordance with its mandate to provide guidance to
      Member States on health policy matters, WHO issues a series of regularly updated
      position papers on vaccines and combinations of vaccines against diseases that
      have an international public health impact. These papers are concerned primarily
      with the use of vaccines in large-scale immunization programmes; they summarize
      essential background information on diseases and vaccines, and conclude with
      WHO's current position on the use of vaccines in the global context. This
      position paper reflects the global switch from trivalent to bivalent OPV which
      took place in April 2016. Recommendations on the use of polio vaccines have been
      discussed on multiple occasions by SAGE, most recently in October 2016; evidence
      presented at these meetings can be accessed at:
      http://www.who.int/immunization/sage/previous/en/index.html.

PMID- 27894721
TI  - Vaccination against hepatitis B virus among people who inject drugs - A 20year
      experience from a Swedish needle exchange program.
AB  - BACKGROUND: People who inject drugs (PWID) are at particular risk of hepatitis B
      virus (HBV) acquisition, but often have poor access or adherence to HBV
      vaccination. Vaccination against HBV has been offered at a major Swedish needle
      exchange program (NEP) since 1994. The aim of this study was to evaluate vaccine
      completion and response rates, and the effect of sequential booster doses to non
      responders to the standard vaccination schedule. METHODS: PWID enrolled in the
      NEP 1994-2013, without serological markers for HBV at baseline (negative for
      HBsAg/anti-HBc/anti-HBs), were offered a three-dose standard intramuscular
      vaccination schedule (Engerix(r)-B, GSK, 20MUg/mL, intended to be received at
      months 0, 1 and 6). Vaccination response was defined as protective levels of anti
      HBs (?10mIU/mL). Up to three booster doses were then offered for non-responders,
      each followed by anti-HBs testing. RESULTS: HBV data was available for 2352
      identifiable individuals at NEP enrolment, of whom 1516 (64.5%) had no markers
      for previous HBV exposure or vaccination. Vaccination was initiated for 1142
      (75.3%) individuals and 898 (59.2%) completed the standard vaccination schedule.
      Post-vaccination anti-HBs levels were available from 800 individuals, with 598
      (74.8%) responding to the basic vaccination schedule. After up to three booster
      doses a total of 676 (84.5%) individuals achieved protective anti-HBs levels. Non
      response to vaccination was associated with higher age and anti-HCV positivity
      (p<0.001). Eighteen incident cases of HBV infection were observed among vaccine
      non-responders, as well as 30 cases among those who had not completed
      vaccination. CONCLUSION: We demonstrate the feasibility of including HBV
      vaccination in the services offered by a NEP, with completion of vaccination in a
      majority of HBV-susceptible PWID. The response to HBV vaccination among PWID was
      relatively low; however, the addition of up to three booster doses improved the
      response rate from 74.8 to 84.5%.

PMID- 27894723
TI  - Plastic debris and microplastics along the beaches of the Strait of Hormuz,
      Persian Gulf.
AB  - Currently little is known about the prevalence of plastics and microplastics
      (MPs) in the Persian Gulf. Five sampling stations were selected along the Strait
      of Hormuz (Iran) that exhibited different levels of industrialization and
      urbanization, and included a marine protected area. Debris was observed and
      sediments were collected for MPs extraction via fluidization/floatation
      methodology. The order of MP abundance (par/kg) generally reflected the level of
      anthropogenic activity: Bostanu (1258+/-291)>Gorsozan (122+/-23)>Khor-e-Yekshabeh
      (26+/-6)>Suru (14+/-4)>Khor-e-Azini (2+/-1). Across all sites fibers dominated
      (83%, 11% film, 6% fragments). FT-IR analysis showed polyethylene (PE), nylon,
      and PET (polyethylene terephthalate) were the commonly recovered polymers. Likely
      sources include beach debris, discarded fishing gear, and urban and industrial
      outflows that contain fibers from clothes. This study provides a 'snapshot' of MP
      pollution and longitudinal studies are required to fully understand plastic
      contamination in the region.

PMID- 27894722
TI  - Impact of bio-palladium nanoparticles (bio-Pd NPs) on the activity and structure
      of a marine microbial community.
AB  - Biogenic palladium nanoparticles (bio-Pd NPs) represent a promising catalyst for
      organohalide remediation in water and sediments. However, the available
      information regarding their possible impact in case of release into the
      environment, particularly on the environmental microbiota, is limited. In this
      study the toxicity of bio-Pd NPs on the model marine bacterium V. fischeri was
      assessed. The impacts of different concentrations of bio-Pd NPs on the
      respiratory metabolisms (i.e. organohalide respiration, sulfate reduction and
      methanogenesis) and the structure of a PCB-dechlorinating microbial community
      enriched form a marine sediment were also investigated in microcosms mimicking
      the actual sampling site conditions. Bio-Pd NPs had no toxic effect on V.
      fischeri. In addition, they had no significant effects on PCB-dehalogenating
      activity, while showing a partial, dose-dependent inhibitory effect on sulfate
      reduction as well as on methanogenesis. No toxic effects by bio-Pd NPs could be
      also observed on the total bacterial community structure, as its biodiversity was
      increased compared to the not exposed community. In addition, resilience of the
      microbial community to bio-Pd NPs exposure was observed, being the final
      community organization (Gini coefficient) of samples exposed to bio-Pd NPs
      similar to that of the not exposed one. Considering all the factors evaluated,
      bio-Pd NPs could be deemed as non-toxic to the marine microbiota in the
      conditions tested. This is the first study in which the impact of bio-Pd NPs is
      extensively evaluated over a microbial community in relevant environmental
      conditions, providing important information for the assessment of their
      environmental safety.

PMID- 27894724
TI  - Susceptibility of seagrass to oil spills: A case study with eelgrass, Zostera
      marina in San Francisco Bay, USA.
AB  - Existing literature illustrates inconsistent responses of seagrasses to oil
      exposure, both in the field and in the laboratory. Here, we add a new study that
      combined morphometric, demographic and photophysiology assessments to determine
      the potential oiling impacts to eelgrass (Zostera marina) from the 2007 Cosco
      Busan event in San Francisco Bay. Shoot densities, reproductive status, and
      rhizome elongation of Z. marina were examined at sites with pre-spill data, and
      eelgrass photosynthetic efficiency was measured post-spill. Shoot densities and
      percent elongation of rhizome internodes formed after the oil spill varied but
      with no consistent relationship to adjacent shoreline cleanup assessment team
      (SCAT) oiling categories. Similarly, differences in seagrass photosynthetic
      efficiency were not consistent with SCAT oiling categories. While thresholds for
      negative impacts on seagrass in general remain to be defined, conclusive oiling
      indicators for degree and duration of exposure would be important considerations
      and need examination under controlled study.

PMID- 27894725
TI  - Occurrence of antiparasitic pesticides in sediments near salmon farms in the
      northern Chilean Patagonia.
AB  - Growth of the aquaculture industry has triggered the need for research into the
      potential environmental impact of chemicals used by salmon farms to control
      diseases. In this study, the antiparasitic pesticides emamectin benzoate (EB),
      diflubenzuron (DI), teflubenzuron (TE), and cypermethrin (CP) were measured in
      sediments near salmon cages in southern Chile. Concentrations for EB were between
      2.2 and 14.6ngg-1, while the benzoylphenyl ureas DI and TE were detected in the
      ranges of 0.1 to 1.2ngg-1 and 0.8 to 123.3ngg-1, respectively. These results were
      similar to data reported for the Northern Hemisphere. On the other hand, the
      pyrethroid CP was detected in higher concentrations, ranging from 18.0 to
      1323.7ngg-1. According to reported toxicity data, this range represents a
      potential risk for benthic invertebrates. This report is the first baseline
      attempt at assessing antiparasitic pesticide levels in the Chilean Patagonia.

PMID- 27894726
TI  - Petroleum hydrocarbon persistence following the Deepwater Horizon oil spill as a
      function of shoreline energy.
AB  - An important aspect of oil spill science is understanding how the compounds
      within spilled oil, especially toxic components, change with weathering. In this
      study we follow the evolution of petroleum hydrocarbons, including n-alkanes,
      polycyclic aromatic hydrocarbons (PAHs) and alkylated PAHs, on a Louisiana beach
      and salt marsh for three years following the Deepwater Horizon spill. Relative to
      source oil, we report overall depletion of low molecular weight n-alkanes and
      PAHs in all locations with time. The magnitude of depletion, however, depends on
      the sampling location, whereby sites with highest wave energy have highest
      compound depletion. Oiled sediment from an enclosed bay shows high enrichment of
      high molecular weight PAHs relative to 17alpha(H),21beta(H)-hopane, suggesting
      the contribution from sources other than the Deepwater Horizon spill, such as
      fossil fuel burning. This insight into hydrocarbon persistence as a function of
      hydrography and hydrocarbon source can inform policy and response for future
      spills.

PMID- 27894727
TI  - Factors associated with gait speed recovery after total knee arthroplasty: A
      longitudinal study.
AB  - OBJECTIVES: Gait speed limitations can remain significant issues after a total
      knee arthroplasty (TKA) but their associated factors are not well understood.
      This study aimed to identify the factors associated with acute gait speed
      recovery post-TKA. METHODS: We performed a prospective longitudinal study of 1765
      patients who underwent primary TKA between July 2013 and July 2015. At 4, 8, 12,
      and 16 weeks postsurgery, fast gait speed was measured. The factors associated
      with gait speed over time since TKA were identified using multivariable
      generalized least squares modeling. RESULTS: Lower postoperative quadriceps
      strength and knee flexion range of motion were closely associated with lower gait
      speed over time (0.084m/s, 0.064m/s, and 0.055m/s change in gait speed per
      interquartile range change in ipsilateral quadriceps strength, contralateral
      quadriceps strength, and knee flexion range of motion, respectively). Additional
      strong predictors of lower gait speed included older age (0.11m/s), lower levels
      of preoperative Short Form 36 physical function (0.066m/s), greater body mass
      (0.046m/s), and the preoperative use of a walking aid (overall P < 0.001).
      Patients who reported that they limited their daily activities due to a fear of
      falling also had poorer gait speed (0.033m/s and 0.054m/s slower gait speed for
      "Occasional" and "Often" categories, respectively, vs. "None"). CONCLUSIONS: Gait
      speed recovery post-TKA is driven by both physical and psychological factors,
      suggesting that identifying and treating the underlying physical and cognitive
      causes of gait speed limitations may be crucial to optimize functional recovery.

PMID- 27894729
TI  - Effect of diagnostic cone-beam computed tomography protocols on image quality,
      patient dose, and lesion detection.
AB  - OBJECTIVE: To evaluate the effect of cone-beam computed tomography (CBCT) image
      acquisition protocols on image quality, lesion detection, delineation, and
      patient dose. METHODS: 100-patients and a CTDI phantom combined with an electron
      density phantom were examined using four different CBCT-image acquisition
      protocols during image-guided transarterial chemoembolization (TACE). Protocol-1
      (time: 6s, tube rotation: 360 degrees ), protocol-2 (5s, 300 degrees ), protocol
      3 (4s, 240 degrees ) and protocol-4 (3s, 180 degrees ) were used. The protocols
      were first investigated using a phantom. The protocols that were found to be
      clinically appropriate in terms of image quality and radiation dose were then
      assessed on patients. A higher radiation dose and/or a poor image quality were
      inappropriate for the patient imaging. Patient dose (patient-entrance dose and
      dose-area product), image quality (Hounsfield Unit, noise, signal-to-noise ratio
      and contrast-to-noise ratio), and lesion delineation (tumor-liver contrast) were
      assessed and compared using appropriate statistical tests. Lesion detectability,
      sensitivity, and predictive values were estimated for CBCT-image data using pre
      treatment patient magnetic resonance imaging. RESULTS: The estimated patient dose
      showed no statistical significance (p>0.05) between protocols-2 and -3; the
      assessed image quality between these protocols manifested insignificant
      difference (p>0.05). Two other phantom protocols were not considered for patient
      imaging due to significantly higher dose (protocols-1) and poor image quality
      (protocol-4). Lesion delineation and detection were insignificant (p>0.05)
      between protocols-2 and -3. Lesion sensitivities generated were 81-89% (protocol
      2) and 81-85% (protocol-3) for different lesion types. CONCLUSION: Data
      acquisition using protocols-2 and -3 provided good image quality, lesion
      detection and delineation with acceptable patient dose during CBCT-imaging mainly
      due to similar frame numbers acquired.

PMID- 27894728
TI  - Bone Density in Patients With Berardinelli-Seip Congenital Lipodystrophy Is
      Higher in Trabecular Sites and in Type 2 Patients.
AB  - Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare autosomal recessive
      syndrome characterized by a difficulty storing lipid in adipocytes, low body fat,
      hypoleptinemia, and hyperinsulinemia. We report here laboratory, bone mineral
      density (BMD), and bone mineral content findings of 21 patients (24.1 +/- 8.4 yr
      old, 14 females, 18 diabetics, 5.3% total body fat) with BSCL. The mean leptin
      was very low (0.91 +/- 0.42 ng/mL), and the mean values of the Z-scores for all
      studied sites were positive, except for the 33% radius (Z-score -0.5 standard
      deviation [SD]). Twelve patients (57.1%) had a BMD Z-score higher than +2.5 SD in
      at least 1 site. There was no significant difference in the Z-scores between
      males and females. None of type 1 (AGPAT2) patients had Z-scores higher than +2.5
      SD, and these patients had a smaller Z-score of BMD total body (0.26 SD vs 1.90
      SD, p = 0.022) and of bone mineral content (1.59 SD vs 3.3 SD, p = 0.032) than
      type 2 (seipin) patients. Insulin, as well as HOMAIR (homeostasis model
      assessment), correlated positively with the BMD of all sites, except for the 33%
      radius. Z-Scores on this site (33% radius) were the smallest of all. More than
      half of our patients with BSCL have BMD Z-scores higher than +2.5 SD on at least
      1 site, and this increase is more pronounced in the trabecular sites and in type
      2 patients.

PMID- 27894730
TI  - Living With Chronic Pain After Spinal Cord Injury: A Mixed-Methods Study.
AB  - OBJECTIVE: To identify the relative importance of positive (facilitators) and
      negative (barriers) contributors to living with chronic pain after spinal cord
      injury (SCI). DESIGN: Mixed-methods: (1) Qualitative (n=35): individual,
      semistructured, open-ended interviews identifying facilitator/barrier themes; (2)
      Quantitative (n=491): converting the most common themes into statements and
      quantifying agreement with these in an online survey to determine relative
      importance, underlying dimensions, and their associations with perceived
      difficulty in dealing with pain. SETTING: University-based research setting and
      general community. PARTICIPANTS: Volunteers (N=526) with SCI experiencing
      moderate to severe chronic pain. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Interview guides, facilitator/barrier statements, and pain inventories.
      RESULTS: Exploratory factor analyses reduced agreement ratings into 4
      facilitators (information regarding pain and treatments, resilience, coping,
      medication use) and 5 barriers (poor health care communication, pain impact and
      limitations, poor communication about pain, difficult nature of pain, treatment
      concerns). Greater "pain impact and limitations," "difficult nature of pain,"
      "poor communication from provider," lower "resilience," greater "medication use,"
      and younger age predicted greater difficulty in dealing with pain (r=.75;
      F=69.02; P<.001). CONCLUSIONS: This study revealed multiple facilitators and
      barriers to living with chronic pain after SCI. The principal barrier, "poor
      health care communication," indicated that consumers do not receive adequate
      information from their health care providers regarding pain. "Information
      regarding pain and treatments" had greater agreement scores and factor loadings
      than all other facilitators, indicating that most participants view provider
      patient communication and educational efforts regarding pain and pain management
      as priorities and critical needs. Further initiatives in these areas are
      important for improving pain management post-SCI.

PMID- 27894731
TI  - Content and Evaluation of the Benefits of Effective Exercise for Older Adults
      With Knee Pain Trial Physiotherapist Training Program.
AB  - OBJECTIVE: To explore whether participating in the Benefits of Effective Exercise
      for knee Pain (BEEP) trial training program increased physiotherapists' self
      confidence and changed their intended clinical behavior regarding exercise for
      knee pain in older adults. DESIGN: Before/after training program evaluation.
      Physiotherapists were asked to complete a questionnaire before the BEEP trial
      training program, immediately after, and 12 to 18 months later (postintervention
      delivery in the BEEP trial). The questionnaire included a case vignette and
      associated clinical management questions. Questionnaire responses were compared
      over time and between physiotherapists trained to deliver each intervention
      within the BEEP trial. SETTING: Primary care. PARTICIPANTS: Physiotherapists
      (N=53) who completed the BEEP trial training program. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Self-confidence in the diagnosis and
      management of knee pain in older adults; and intended clinical behavior measured
      by a case vignette and associated clinical management questions. RESULTS: Fifty
      two physiotherapists (98%) returned the pretraining questionnaire, and 44 (85%)
      and 39 (74%) returned the posttraining and postintervention questionnaires,
      respectively. Posttraining, self-confidence in managing older adults with knee
      pain increased, and intended clinical behavior regarding exercise for knee pain
      in older adults appeared more in line with clinical guidelines. However, not all
      positive changes were maintained in the longer-term. CONCLUSIONS: Participating
      in the BEEP trial training program increased physiotherapists' self-confidence
      and changed their intended clinical behavior regarding exercise for knee pain,
      but by 12 to 18 months later, some of these positive changes were lost. This
      suggests that brief training programs are useful, but additional strategies are
      likely needed to successfully maintain changes in clinical behavior over time.

PMID- 27894732
TI  - Tele-Assessment of the Berg Balance Scale: Effects of Transmission
      Characteristics.
AB  - OBJECTIVE: To compare Berg Balance Scale (BBS) rating using videos with differing
      transmission characteristics with direct in-person rating. DESIGN: Repeated
      measures study for the assessment of the BBS in 8 configurations: in person, high
      definition video with slow motion review, standard-definition videos with varying
      bandwidths and frame rates (768 kilobytes per second [kbps] videos at 8, 15, and
      30 frames per second [fps], 30 fps videos at 128, 384, and 768 kbps). SETTING:
      Medical center. PARTICIPANTS: Patients with limitations (N=45) in >=1 of 3
      specific aspects of motor function: fine motor coordination, gross motor
      coordination, and gait and balance. INTERVENTIONS: Not applicable. MAIN OUTCOMES
      MEASURES: Ability to rate the BBS in person and using videos with differing
      bandwidths and frame rates in frontal and lateral views. RESULTS: Compared with
      in-person rating (7%), 18% (P=.29) of high-definition videos and 37% (P=.03) of
      standard-definition videos could not be rated. Interrater reliability for the
      high-definition videos was .96 (95% confidence interval, .94-.97). Rating failure
      proportions increased from 20% in videos with the highest bandwidth to 60%
      (P<.001) in videos with the lowest bandwidth, with no significant differences in
      proportions across frame rate categories. Both frontal and lateral views were
      critical for successful rating using videos, with 60% to 70% (P<.001) of videos
      unable to be rated on a single view. CONCLUSIONS: Although there is some loss of
      information when using videos to rate the BBS compared to in-person ratings, it
      is feasible to reliably rate the BBS remotely in standard clinical spaces.
      However, optimal video rating requires frontal and lateral views for each
      assessment, high-definition video with high bandwidth, and the ability to carry
      out slow motion review.

PMID- 27894733
TI  - The Missing Antibody: The Pitfalls of ANCA Testing.

PMID- 27894734
TI  - Training Geriatric Cardiologists for an Aging Population: Time to Get Going.

PMID- 27894735
TI  - The New Trend in Medicine.

PMID- 27894736
TI  - In-Hospital Mortality with Deep Venous Thrombosis.
AB  - BACKGROUND: Little is known about the in-hospital mortality of deep venous
      thrombosis in recent years. This investigation was undertaken to determine trends
      in in-hospital mortality in patients with deep venous thrombosis and mortality
      according to age. METHODS: Administrative data were analyzed from the National
      (Nationwide) Inpatient Sample, 2003-2012. We determined in-hospital all-cause
      mortality according to year and age among patients with a primary (first-listed)
      diagnosis of deep venous thrombosis. We analyzed all such patients and we
      analyzed those who had none of the comorbid conditions listed in the Charlson
      Comorbidity Index. RESULTS: From 2003-2012, 1,603,690 hospitalized patients had a
      primary diagnosis of deep venous thrombosis. All-cause in-hospital mortality
      decreased from 1.3% in 2003 to 0.6% in 2012. Mortality increased with age from
      0.1% in those aged 18-20 years to 1.5% in those over age 80 years. All-cause in
      hospital mortality in those with no comorbid conditions according to the Charlson
      Comorbidity Index (1,094,184 patients) decreased from 1.1% in 2003 to 0.5% in
      2012. Presumably, these deaths were from pulmonary embolism. All-cause mortality
      in those with no comorbid conditions increased with age from 0.1% in those aged
      18-20 years to 1.4% in those over aged 80 years. CONCLUSION: All-cause death and
      death due to pulmonary embolism in patients hospitalized with a primary diagnosis
      of deep venous thrombosis decreased from 2003-2012. The death rate increased with
      age. The decreased mortality over the period of investigation may have resulted
      from a shift toward use of low-molecular-weight heparins and newer
      anticoagulants.

PMID- 27894737
TI  - A Word of Caution When Prescribing High-Dose Vitamin D.

PMID- 27894738
TI  - Patients with Multiple Intracranial Aneurysms Presenting Initial Worse Clinical
      Condition as a Result of a Ruptured Aneurysm.

PMID- 27894739
TI  - In Reply to "Patients with Multiple Intracranial Aneurysms Presenting Initial
      Worse Clinical Condition as a Result of a Ruptured Aneurysm".

PMID- 27894740
TI  - Reply to "Is mean platelet volume a prognostic marker for hemodialysis patients?"

PMID- 27894741
TI  - Dementia and death: Separate sides of the atrial fibrillation coin?

PMID- 27894742
TI  - Metabolic state defines the response of rabbit ovarian cells to leptin.
AB  - Leptin is a hormone that mediates the effect of the metabolic state on several
      biological functions, including reproduction. Leptin affects reproductive
      functions via alterations in the release of hormonal regulators. However, the
      extent to which caloric restriction (CR) can affect the complex processes of
      reproduction by other mechanisms, such as altering ovarian functions via direct
      binding/response to leptin, is unknown. Therefore, the aim of the present study
      was to show basic ovarian cell functions and CR on the response of ovarian cells
      to leptin. Female rabbits were subjected to 50% CR restriction for 10days before
      ovulation. On the day of ovulation, both control and CR animals were sacrificed.
      Isolated granulosa cells were cultured for 2days with and without leptin
      (100ng/ml), and the accumulation of various markers was evaluated using
      immunocytochemistry; i.e., cell proliferation (PCNA and cyclin B1), apoptosis
      (bax), MAP/ERK1,2 kinase (MAPK), protein kinase A (PKA), and IGF-I. In addition,
      the release of IGF-I and estradiol (E2) by cells cultured with and without leptin
      (1, 10, 100, 1000, or 10,000ng/ml) was assessed by radioimmunoassay (RIA). In the
      granulosa cells of control animals, leptin promoted cyclin B1, MAPK, and PKA
      accumulation, but not that of PCNA, and reduced bax and IGF-I accumulation. These
      cells responded to leptin by increased IGF-I, but not E2 release. In cells of CR
      animals, leptin increased cyclin B1 accumulation, but decreased PCNA, MAPK, and
      IGF-I expression. Bax and PKA were not affected. Leptin resulted in a decrease in
      IGF-I release. CR modulated the influence of leptin on E2 release dose
      dependently, i.e., E2 increased at 10 and decreased at 10,000ng/ml. Therefore, CR
      modified the influence of leptin on PCNA, E2, bax, PKA, MAPK, and IGF-I release,
      but it did not change the effect of leptin on cyclin B1 and IGF-I accumulation
      within the cells. Our data showed that leptin directly affected proliferation,
      apoptosis, and hormone release by ovarian cells, probably via PKA- and MAPK
      dependent pathways. Furthermore, it was demonstrated that nutrition could
      influence reproduction by affecting the response of ovarian cells to leptin.

PMID- 27894743
TI  - Transfer factors for natural radioactivity into date palm pits.
AB  - Palm pits are used in various human and animal feed products. In this study, the
      natural radioactivity levels from soil and date palm pits of 9 samples collected
      from major date palm farms in three different regions (Buraidah, Al-Zulfi and Al
      Majmaah) of Saudi Arabia were determined by using the high purity germanium
      (HPGe) gamma-ray spectrometer. The mean activity concentrations of 226Ra, 232Th,
      137Cs and 40K in soil samples were 12.8 +/- 2.2, 10.2 +/- 2.1, 0.28 +/- 0.10 and
      329 +/- 87 Bg kg-1, respectively. Similarly the mean activity concentrations of
      226Ra, 232Th, and 40K in date palm pits were 5.6 +/- 1.2, 2.8 +/- 0.4 and 181 +/-
      17 Bq kg-1, respectively, whereas 137Cs could not be detected. The geometric mean
      of TF values (geometric standard deviation in parentheses) of 226Ra, 232Th, and
      40K were 0.33 (2.1), 0.22 (1.8) and 0.51 (2.0), respectively.

PMID- 27894744
TI  - [Vitamin D deficiency and morbimortality in critically ill paediatric patients].
AB  - OBJECTIVES: To determine the prevalence and risks factors of vitamin D
      deficiency, as well as its relationship with morbidity and mortality in a PICU.
      MATERIAL AND METHODS: An observational prospective study in a tertiary children's
      University Hospital PICU conducted in two phases: i: cohorts study, and ii:
      prevalence study. The study included 340 critically ill children with ages
      comprising 6 months to 16 years old. EXCLUSION CRITERIA: Chronic kidney disease,
      known parathyroid disorders, and vitamin D supplementation. Total 25
      hydroxyvitamin D [25(OH)D] was measured in the first 48hours of admission to a
      PICU. Parathormone, calcium, phosphate, blood gases, blood count, C-reactive
      protein, and procalcitonin were also analysed. A record was also made of
      demographic features, characteristics of the episode, and complications during
      the PICU stay. RESULTS: The overall prevalence rate of vitamin D deficiency was
      43.8%, with a mean of 22.28 (95% CI 21.15-23.41) ng/ml. Patients with vitamin D
      deficiency were older (61 vs 47 months, P=.039), had parents with a higher level
      of academic studies (36.5% vs 20%, P=.016), were admitted more often in winter
      and spring, had a higher PRISM-III (6.8 vs 5.1, P=.037), a longer PICU stay (3 vs
      2 days, P=.001), and higher morbidity (61.1% vs 30.4%, P<001) than the patients
      with sufficient levels of 25(OH)D. Patients who died had lower levels of 25(OH)D
      (14+/-8.81ng/ml versus 22.53+/-10.53ng/ml, P=.012). Adjusted OR for morbidity was
      5.44 (95%CI; 2.5-11.6). CONCLUSIONS: Vitamin D deficiency is frequent in
      critically ill children, and it is related to both morbidity and mortality,
      although it remains unclear whether it is a causal relationship or it is simply a
      marker of severity in different clinical situations.

PMID- 27894745
TI  - CEVL interactive - Promoting effective teamwork to perform robot assisted
      laparoscopic pyeloplasty in pediatric urology.

PMID- 27894746
TI  - Roux-en-Y gastric bypass versus calorie restriction: support for surgery per se
      as the direct contributor to altered responses of insulin and incretins to a
      mixed meal.
AB  - OBJECTIVE: To study the immediate effects of Roux-en-Y gastric bypass (RYGB) on
      glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared
      with the effects of calorie restriction (CR). SETTING: University-affiliated
      bariatric surgery clinic. BACKGROUND: RYGB induces remission of type 2 diabetes
      (T2D) long before significant weight loss occurs. The time course and underlying
      mechanisms of this remission remain enigmatic. A prevailing theory is that
      secretory patterns of incretin hormones are altered due to rearrangement of the
      gastrointestinal tract. To what extent reduced calorie intake contributes to the
      remission of T2D is unknown. METHODS: Nine normoglycemic patients and 10 T2D
      patients were subjected to mixed-meal tests (MMT) 4 weeks before surgery before
      initiation of a very low calorie diet regimen (MMT-4 w), 1 day before surgery on
      a very low calorie diet regimen (MMT-1 d), on the morning of the first day after
      surgery (MMT+1 d; first postsurgical meal), and 6 weeks after surgery (MMT+6 w).
      Insulin, glucose, active glucagon-like peptide 1 (GLP-1), and glucose-dependent
      insulinotropic polypeptide (GIP) were measured. RESULTS: CR lowered insulin in
      T2D patients, whereas glucose, GIP, and GLP-1 were unaffected. RYGB immediately
      increased plasma insulin and GIP. The GLP-1 response was delayed compared with
      the GIP response. T2D patients exhibited lower insulin responses after RYGB
      compared with normoglycemic patients. GIP responses were similar in both groups
      at all occasions, whereas T2D patients displayed markedly elevated GLP-1
      responses 6 weeks after RYGB. Glucose was unaffected by CR and RYGB in both
      groups. Insulin sensitivity was unaffected by CR but improved with RYGB.
      CONCLUSION: RYGB exerts powerful and immediate effects on insulin and incretin
      responses to food, independently of changes caused by CR.

PMID- 27894747
TI  - Reduction of coagulability state one year after bariatric surgery.
AB  - BACKGROUND: Obese patients are in a hypercoagulable state relative to normal
      weight patients. Low-grade inflammation may be a key factor for this condition.
      OBJECTIVES: Our study aimed to compare the coagulability state of morbidly obese
      patients before and 1 year after bariatric surgery (BS) using the Thrombin
      Generation (TG) test, a validated method to assess coagulation in vitro. SETTING:
      University hospital. METHODS: All patients undergoing BS between September 1,
      2014 and April 30, 2015 were eligible for this prospective study (n = 42). Two
      distinct reagents were used for TG initiation based on the tissue factor
      concentration (Reagents LOW and HIGH). The main outcomes were endogenous thrombin
      potential (ETP) and peak height of TG. The rate of follow-up after one year was
      97%. RESULTS: One year after surgery, %weight loss was 32.5+/-8.4%; CRP decreased
      from 9.0 (3.7-12.9) to 1.1 (0.3-2.8) mg/mL (P<.001) and fibrinogen from 4.2+/-.8
      to 3.5+/-.8 g/L (P<.001). The ETP (%) decreased from (108.0 (95.0-117.0) to 78.0
      (71.0-98.0) (P<.001) (LOW reagent) and from 113.0 (103.0-134.0) to 96.0 (86.0
      107.0) (P<.001) (HIGH reagent). Peak height (%) decreased from (117.0 (92.0
      139.0) to 82.0 (70.0-111.0) (P = .003) (LOW reagent) and from 106.0 (96.0-118.0)
      to 97.0 (87.8-105.2) (P = .003) (HIGH reagent). CONCLUSION: Our study shows a
      significant reduction in TG potential one year after BS in morbidly obese
      patients. Reduction of low grade inflammation may be one of the underlying
      mechanisms.

PMID- 27894748
TI  - CCR5-Delta32 gene polymorphism is related to celiac disease and autoimmune
      thyroiditis coincidence in patients with type 1 diabetes.
AB  - AIM: The aim of the study was to assess the relationship between CCR5-Delta32
      polymorphism and the coincidence of celiac and autoimmune thyroid diseases with
      type 1 diabetes mellitus (T1D) in children. METHODS: 420 children with T1D aged
      15.5+/-3.0years and 350 healthy controls were studied. Characterization of CCR5
      Delta32 genotypes (rs333) was analyzed by polymerase chain reaction (PCR).
      RESULTS: The allele frequency was significantly different in diabetic children as
      compared to the healthy controls (p<0.0001). We found negative association
      between T1D and Delta32 allele (OR=0.383; 95% CI=0.268-0.549). Besides, we
      observed alterations in the frequencies of CCR5-Delta32 genotypes due to celiac
      and autoimmune thyroid diseases. The risk of celiac disease for patient carriers
      of the 32-bp deletion was more than threefold higher than for noncarriers
      (OR=3.490; 95% CI=1.357-8.859; p=0.009). Similar results were obtained in the
      case of autoimmune thyroiditis. The risk of autoimmune thyroiditis for patient
      carriers of the 32-bp deletion was also more than threefold higher than for
      noncarriers (OR=3.466; 95% CI=1.754-6.849; p=0.0004). CONCLUSIONS: The findings
      of our studies suggest that the CCR5-Delta32 polymorphism is associated with type
      1 diabetes mellitus and the Delta32 allele increases the risk of celiac disease
      and autoimmune thyroid disorders in patients with T1D.

PMID- 27894749
TI  - The microbiology of diabetic foot infections in patients recently treated with
      antibiotic therapy: A prospective study from India.
AB  - AIM: Clinicians often treat clinically infected diabetic foot ulcers without
      information from cultures of the wound. The results of wound cultures may also be
      affected by previous antibiotic therapy. Thus, we aimed to study the microbial
      isolates, and antimicrobial sensitivity of previously treated patients with a
      clinically infected DFU. RESEARCH DESIGN AND METHODS: 293 consecutive patients
      with clinically infected DFU on prior antimicrobial treatment within the
      immediate past few days for a duration greater than one week were evaluated for
      microbial etiology, antibiotic sensitivity and final outcomes. Appropriate tissue
      samples i.e. purulent drainage, soft-tissue and/ or bone were obtained for
      aerobic/anaerobic cultures and antimicrobial sensitivities. 71 patients with
      missing prior antibiotic data were excluded. RESULTS: 313 tissue samples obtained
      from 222 patients isolated 317 causative organisms. Most of the culture results
      from tissue specimens were mono-microbial (93.2%) compared to 37% in our previous
      cohort of 60 patients. Pseudomonas aeruginosa was the most common organism
      isolated on culture of bone (26.9%) or soft tissue (23.2%) specimen,
      respectively. Only 23% and 64% of P. aeruginosa isolates and 5.6% and 44% of
      Acinetobacter sp. were sensitive to quinolones and cephalosporins, respectively.
      CONCLUSIONS: Clinically infected DFU recently treated with antibiotics have
      predominant monomicrobial and multi drug-resistant infection. Quinolones as an
      empirical antibiotic choice may not be appropriate in this setting.

PMID- 27894750
TI  - Risk factors for autonomic and somatic nerve dysfunction in different stages of
      glucose tolerance.
AB  - AIM: The present study evaluates autonomic and somatic nerve function in
      different stages of glucose tolerance and its correlation with different cardio
      metabolic parameters. MATERIAL AND METHODS: Four hundred seventy-eight subjects,
      mean age 49.3+/-13.7years and mean BMI 31.0+/-6.2kg/m2, divided according to
      glucose tolerance: 130 with normal glucose tolerance (NGT), 227 with prediabetes
      (125 with impaired fasting glucose (IFG) and 102 with isolated impaired glucose
      tolerance (iIGT)), and 121 with newly-diagnosed T2D (NDT2D), were enrolled.
      Glucose tolerance was studied during OGTT. Antropometric indices, blood pressure,
      HbA1c, serum lipids, hsCRP and albumin-to-creatinine ratio were assessed. Body
      composition was estimated by a bioimpedance method (InBody 720, BioSpace). Tissue
      AGEs accumulation was assessed by skin autofluorescence (AGE-Reader
      DiagnOpticsTM). Electroneurography was performed by electromyograph Dantec
      Keypoint. Cardiovascular autonomic neuropathy (CAN) was assessed by ANX-3.0
      method applying standard clinical tests. RESULTS: CAN was found in 12.3% of NGT,
      19.8% of prediabetes (13.2% of IFG and 20.6% of iIGT), and 32.2% of NDT2D. The
      prevalence of diabetic sensory polyneuropathy (DSPN) was 5.7% in prediabetes and
      28.6% in NDT2D. The panel of age, QTc interval, waist circumference, diastolic
      blood pressure, and 120-min plasma glucose was related to sympathetic activity (F
      [5451]=78.50, p<0.001). The panel of age, waist circumference, and QTc interval
      was related to parasympathetic power (F [3453]=132.26, p<0.001). HbA1c and age
      were related to sural SNAP (F [2454]=15.12, p<0.001). HbA1c and AGEs were related
      to sural SNCV (F [2454]=12.18, p<0.001). CONCLUSIONS: Our results demonstrate a
      high prevalence of autonomic and sensory nerve dysfunction in early stages of
      glucose intolerance. Age, postprandial glycemia, central obesity, diastolic blood
      pressure and QTc interval outline as predictive markers of CAN; hyperglycemia,
      glycation and age of DSPN.

PMID- 27894752
TI  - Trends in cervical cancer incidence in younger US women from 2000 to 2013.
AB  - OBJECTIVE: This study aimed to assess the temporal trends in invasive cervical
      cancer (ICC) incidence rates among 21-25year-olds. US guidelines no longer
      recommend screening prior to age 21, and concerns have been raised that delayed
      screening initiation may increase ICC incidence among young women. METHODS: This
      study utilized ICC incidence data from 18 US population-based cancer registries
      in SEER from 2000 to 2013 and Pap test prevalence data from the Behavioral Risk
      Factor Surveillance System from 1996 to 2012. Trends were evaluated with annual
      percent changes (APCs) using Joinpoint regression. RESULTS: The prevalence of
      never having a Pap test before age 21 increased from 22.0% in 1996-2004 to 38.3%
      in 2006-2012 (APC=+5.48, 95%CI=+4.20, +7.50). Despite this decline in screening,
      ICC incidence among 21-23year olds significantly declined between 2000 and 13
      (APC=-5.36, 95%CI=-7.83,-2.82), particularly from 2006 to 2013 (APC=-9.70, 95%CI=
      15.79, -3.17). ICC incidence remained constant among 24-25year olds (APC=+0.45,
      95%CI=-2.00, 2.97). Compared to women born in 1978-1985, women born in 1986-1991
      had a higher prevalence of never receiving a Pap test prior to 21 (35.4% vs.
      22.1%, p<0.001), but a lower ICC incidence at 21-23 (0.98 vs. 1.55 per 100,000,
      p<0.001). CONCLUSION: While US females born in 1986-1991 were less likely to
      receive a Pap test before age 21, diagnoses of ICC in the early 20s were rare and
      lower than for those born in earlier years. This provides reassurance that the
      updated guidelines to delay screening until 21 has not resulted in a population
      level increase in ICC rates among young women.

PMID- 27894751
TI  - Polymerase epsilon (POLE) ultra-mutation in uterine tumors correlates with T
      lymphocyte infiltration and increased resistance to platinum-based chemotherapy
      in vitro.
AB  - OBJECTIVE: Up to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase
      epsilon-(POLE) mutations. It is currently unknown whether the favorable prognosis
      of POLE-mutated EC is derived from their low metastatic capability, extraordinary
      number of somatic mutations thus imparting immunogenicity, or a high sensitivity
      to chemotherapy. METHODS: Polymerase-chain-reaction-amplification and Sanger
      sequencing were used to test for POLE exonuclease-domain-mutations (exons 9-14)
      131 EC. Infiltration of CD4+ and CD8+ T-lymphocytes (TIL) and PD-1-expression in
      POLE-mutated vs POLE wild-type EC was studied by immunohistochemistry (IHC) and
      the correlations between survival and molecular features were investigated.
      Finally, primary POLE-mutated and POLE-wild-type EC cell lines were established
      and compared in-vitro for their sensitivity to chemotherapy. RESULTS: Eleven POLE
      mutated EC (8.5%) were identified. POLE-mutated tumors were associated with
      improved progression-free-survival (P<0.05) and displayed increased numbers of
      CD4+ (44.5 vs 21.8; P=0.001) and CD8+ (32.8 vs 13.5; P<0.001) TILs when compared
      to wild-type POLE EC. PD-1 receptor was overexpressed in TILs from POLE-mutated
      vs wild-type-tumors (81% vs 28%; P<0.001). Primary POLE tumor cell lines were
      significantly more resistant to platinum-chemotherapy in-vitro when compared to
      POLE-wild-type tumors (P<0.004). CONCLUSIONS: POLE ultra-mutated EC are heavily
      infiltrated with CD4+/CD8+ TIL, overexpress PD-1 immune-check-point (i.e.,
      features consistent with chronic antigen-exposure), and have a better prognosis
      when compared to other molecular subtypes of EC patients. POLE-mutated tumor-cell
      lines are resistant to platinum-chemotherapy in-vitro suggesting that the better
      prognosis of POLE-patients is not secondary to a higher sensitivity to
      chemotherapy but likely linked to enhanced immunogenicity.

PMID- 27894753
TI  - Association between timing of cervical excision procedure to minimally invasive
      hysterectomy and surgical complications.
AB  - OBJECTIVE: To determine if the time interval between excision procedure and
      definitive minimally invasive surgery (MIS) for cervical cancer impacts 30-day
      postoperative complications. METHODS: A retrospective cohort of patients
      diagnosed with cervical cancer from January 2000 to July 2015 was evaluated.
      Patients who underwent a cervical excision procedure followed by definitive MIS
      within 90days were included. Early definitive surgery was defined as <=6 weeks
      following excision procedure, while delayed was defined as 6weeks to 3months. The
      primary outcome was 30-day complications. Statistical analysis included
      descriptive statistics and modified Poission regression. RESULTS: Overall, 138
      patients met inclusion criteria. Of these, 33% (n=46) had early definitive
      surgery and 67% (n=92) had delayed definitive surgery. Median age was 42years
      (range 23-72years) and median BMI was 28kg/m2 (range 16-50kg/m2). Within
      demographic and surgical factors collected, only smoking status differed between
      groups with those in the delayed surgery group more likely to be non-smokers than
      those in the early surgery group (p=0.04). When adjusting for relevant
      demographic and surgical factors, patients in the early group were twice as
      likely to have 30-day complication (aRR 2.6, 95%CI 1.14-5.76, p=0.02). Evaluating
      only women who underwent a radical procedure, 30-day complications remained
      higher in the early surgery group (RR 2.56; 95%CI 1.22-5.38, p=0.01).
      CONCLUSIONS: Performing definitive MIS for cervical cancer within 6weeks after
      cervical excision is associated with increased risk for 30-day complications.
      Providers should consider delaying definitive surgical procedures for at least
      6weeks following excision to reduce surgical complications.

PMID- 27894754
TI  - Composite of Cu metal nanoparticles-multiwall carbon nanotubes-reduced graphene
      oxide as a novel and high performance platform of the electrochemical sensor for
      simultaneous determination of nitrite and nitrate.
AB  - In the present research, we aimed to fabricate a novel electrochemical sensor
      based on Cu metal nanoparticles on the multiwall carbon nanotubes-reduced
      graphene oxide nanosheets (Cu/MWCNT/RGO) for individual and simultaneous
      determination of nitrite and nitrate ions. The morphology of the prepared
      nanocomposite on the surface of glassy carbon electrode (GCE) was characterized
      using various methods including scanning electron microscopy (SEM), atomic force
      microscopy (AFM), and electrochemical impedance spectroscopy. Under optimal
      experimental conditions, the modified GCE showed excellent catalytic activity
      toward the electro-reduction of nitrite and nitrate ions (pH=3.0) with a
      significant increase in cathodic peak currents in comparison with the unmodified
      GCE. By square wave voltammetry (SWV) the fabricated sensor demonstrated wide
      dynamic concentration ranges from 0.1 to 75MUM with detection limits (3Sb/m) of
      30nM and 20nM method for nitrite and nitrate ions, respectively. Furthermore, the
      applicability of the proposed modified electrode was demonstrated by measuring
      the concentration of nitrite and nitrate ions in the tap and mineral waters,
      sausages, salami, and cheese samples.

PMID- 27894755
TI  - DNA damage induced by coal dust, fly and bottom ash from coal combustion
      evaluated using the micronucleus test and comet assay in vitro.
AB  - Coal mining and combustion generating huge amounts of bottom and fly ash are
      major causes of environmental pollution and health hazards due to the release of
      polycyclic aromatic hydrocarbons (PAH) and heavy metals. The Candiota coalfield
      in Rio Grande do Sul, is one of the largest open-cast coal mines in Brazil. The
      aim of this study was to evaluate genotoxic and mutagenic effects of coal, bottom
      ash and fly ash samples from Candiota with the comet assay (alkaline and modified
      version) and micronucleus test using the lung fibroblast cell line (V79).
      Qualitative and quantitative analysis of PAH and inorganic elements was carried
      out by High Performance Liquid Chromatography (HPLC) and by Particle-Induced X
      ray Emission (PIXE) techniques respectively. The samples demonstrated genotoxic
      and mutagenic effects. The comet assay modified using DNA-glicosilase
      formamidopirimidina (FPG) endonuclease showed damage related to oxidative stress
      mechanisms. The amount of PAHs was higher in fly ash followed by pulverized coal.
      The amount of inorganic elements was highest in fly ash, followed by bottom ash.
      It is concluded that the samples induce DNA damage by mechanisms that include
      oxidative stress, due to their complex composition, and that protective measures
      have to be taken regarding occupational and environmental hazards.

PMID- 27894756
TI  - Bioremediation of long-term PCB-contaminated soil by white-rot fungi.
AB  - The objective of this work was to test the PCB-degrading abilities of two white
      rot fungi, namely Pleurotus ostreatus and Irpex lacteus, in real contaminated
      soils with different chemical properties and autochthonous microflora. In
      addition to the efficiency in PCB removal, attention was given to other important
      parameters, such as changes in the toxicity and formation of PCB transformation
      products. Moreover, structural shifts and dynamics of both bacterial and fungal
      communities were monitored using next-generation sequencing and phospholipid
      fatty acid analysis. The best results were obtained with P. ostreatus, which
      resulted in PCB removals of 18.5, 41.3 and 50.5% from the bulk, top (surface) and
      rhizosphere, respectively, of dumpsite soils after 12 weeks of treatment.
      Numerous transformation products were detected (hydoxylated and methoxylated
      PCBs, chlorobenzoates and chlorobenzyl alcohols), which indicates that both fungi
      were able to oxidize and decompose the aromatic moiety of PCBs in the soils.
      Microbial community analysis revealed that P. ostreatus efficiently colonized the
      soil samples and suppressed other fungal genera. However, the same fungus
      substantially stimulated bacterial taxa that encompass putative PCB degraders.
      The results of this study finally demonstrated the feasibility of using this
      fungus for possible scaled-up bioremediation applications.

PMID- 27894757
TI  - Removal of dissolved sulfides in aqueous solution by activated sludge: mechanism
      and characteristics.
AB  - Activated sludge recycling has been developed as a novel technique to directly
      prevent volatile sulfides emission from wastewater influents. In this study,
      mechanisms and characteristics of dissolved sulfides removal in aqueous solution
      by activated sludge were investigated. When DO content in water was 0.49mg/L, 70%
      of removed dissolved sulfides were released back from the activated sludge by
      lowering pH to 1. The SEM/EDS result revealed that removed sulfur was fixed in
      activated sludge and the XPS result showed that fixed sulfur had an oxidation
      state of -2. FTIR results showed that primary amine group (R-NH2) could be one of
      the radical groups bonding sulfides. All these results verified that sulfides
      removal by activated sludge is primarily attributed to adsorption, rather than
      biodegradation, under low DO conditions in 40min. The equilibrium isotherm data
      fit the Langmuir isotherm model well. The maximum adsorption capacity (q0) ranged
      in 25-38mg/g at temperatures of 10-40 degrees C. The adsorption kinetic data fit
      the pseudo-second-order model well. The amounts of adsorbed sulfides at
      equilibrium (qe) were positively proportional to temperature, initial sulfides
      concentration and agitation speed. These results indicate that sulfides
      adsorption could be a chemical sorption or ion exchange process.

PMID- 27894758
TI  - The impact of cardiac risk factors on short-term outcomes for children undergoing
      a Ladd procedure.
AB  - BACKGROUND/PURPOSE: The purpose of this study was to describe the outcomes of
      children with and without congenital heart disease who undergo a Ladd procedure.
      METHODS: The 2012-2014 National Surgical Quality Improvement Program Pediatric
      (NSQIP-P) data were queried for patients undergoing a Ladd procedure. Utilizing
      NSQIP-P definitions, patients were categorized into four cardiac risk groups
      (none, minor, major, severe) based on severity of cardiac anomalies, previous
      cardiac procedure(s), and ongoing cardiac dysfunction. Ladd procedures were
      elective/non-elective. Outcomes included length of stay, adverse events, and
      mortality. RESULTS: 878 patients underwent Ladd procedures. 633 (72%) patients
      had no cardiac risk factors and 84 (10%), 109 (12%), and 52 (6%) had minor,
      major, and severe cardiac risk factors, respectively. Children with congenital
      heart disease experienced increased morbidity and mortality and longer hospital
      stays (all p<0.05). Elective Ladd procedures were associated with similar
      morbidity but shorter length of stay and lower mortality than non-elective
      procedures. Older age at time of operation was associated with fewer adverse
      events. CONCLUSIONS: Although overall mortality remains low, children with higher
      risk cardiac disease experience increased morbidity and mortality when undergoing
      a Ladd procedure. Older age at the time of the Ladd procedure was associated with
      improved outcomes in children.

PMID- 27894759
TI  - Pancreaticoduodenectomy for pediatric and adolescent pancreatic malignancy: A
      single-center retrospective analysis.
AB  - PURPOSE: While pancreaticoduodenectomy (PD) has been extensively studied in
      adults, there are few data pertaining specifically to pediatric patients. We
      retrospectively analyzed PD-associated morbidity and mortality in pediatric
      patients. METHODS: Our analytic cohort included all consecutive patients
      <=18years of age treated at our institution from 1993 to 2015 who underwent PD.
      Patient data (demographics, disease characteristics, surgical and adjuvant
      treatment, length of hospital stay, and postoperative course) were extracted from
      the medical records. RESULTS: We identified 12 children with a median age of
      9years (7 female, 5 male). Final diagnoses were pancreatoblastoma (n=3), solid
      pseudopapillary tumor (n=3), neuroblastoma (n=2), rhabdomyosarcoma (n=2), and
      neuroendocrine carcinoma (n=2). Four patients underwent PD for resection of
      recurrent disease. 75% (9/12 patients) received neoadjuvant therapy. The median
      operative time was approximately 7hours with a mean blood loss of 590cm3. The
      distal pancreas was invaginated into the posterior stomach (n=3) or into the
      jejunum (n=5) or was directly sewn to the jejunal mucosa (n=4). There were no
      operative deaths. There were 4 patients (34%) with grade II complications, 1 with
      a grade IIIb complication (chest tube), and 1 with a grade IV complication
      (reexploration). The most common long-term morbidity was pancreas exocrine
      supplementation (n=10; 83%). Five patients (42%) diagnosed with either solid
      pseudopapillary tumor or rhabdomyosarcoma are currently alive with a mean
      survival of 77.4months. CONCLUSION: Pancreaticoduodenectomy is a feasible
      management strategy for pediatric pancreatic malignancies and is associated with
      acceptable morbidity and overall survival. Long-term outcome is mostly dependent
      on histology of the tumor. LEVEL OF EVIDENCE: Level IV; retrospective study with
      no comparison group.

PMID- 27894760
TI  - Oesophageal atresia with no distal tracheoesophageal fistula: Management and
      outcomes from a population-based cohort.
AB  - PURPOSE: To describe the incidence and outcomes to one-year in infants born with
      oesophageal atresia (OA) with no distal tracheoesophageal fistula within a
      population cohort. METHODS: A subgroup analysis of a prospective multicentre
      population cohort study was undertaken describing the outcomes of infants with OA
      and no tracheoesophageal fistula, (type A) and those with only an upper pouch
      fistula, (type B). MAIN RESULTS: Twenty-one of 151 infants in the whole cohort
      were diagnosed with type A or B oesophageal atresia (14%). Fifteen were type A
      (71%) and six type B (29%). Infants with type B had a shorter gap length than
      those with type A: 2.5 vertebral bodies (2-3) vs. 5 (4-6) (p=0.008). All infants
      with type B OA underwent oesophageal anastomosis, 83% (n=5) as the primary
      procedure. All infants with type A, underwent staged management. Six (40%) had
      delayed primary anastomosis and eight required oesophageal replacement (53%). One
      infant died prior to reconstruction. The median time to delayed primary
      anastomosis in infants with type A or B OA was 82days (75-89days) (n=7). The
      median time to oesophageal replacement was 94days (89-147days) (n=8). Median
      length of stay for infants with type A or B OA from first operation to first
      discharge was 101days (31-123days). CONCLUSIONS: Infants with type B OA had a
      shorter gap length and all were managed with oesophageal anastomosis. OA with no
      distal tracheoesophageal fistula is uncommon at a population level and frequently
      has a complex course. LEVEL OF EVIDENCE: Rating: II.

PMID- 27894761
TI  - Risk factors for recurrence and contralateral inguinal hernia after laparoscopic
      percutaneous extraperitoneal closure for pediatric inguinal hernia.
AB  - BACKGROUND: The use of laparoscopic percutaneous extraperitoneal closure (LPEC)
      for pediatric inguinal hernia has recently been increasing. Recurrence and
      contralateral metachronous inguinal hernia (CMIH) are important problems for
      LPEC. This study analyzed the risk factors for recurrence and CMIH. METHODS: This
      study included 1530 patients. The mean follow-up period was 48months. Of 1530
      patients, 847 were boys and 683 were girls. The mean age at operation was
      3.9years. The asymptomatic contralateral internal ring was routinely observed
      during the operation, and when a patent processus vaginalis (PPV) was confirmed,
      prophylactic surgery was performed. RESULTS: Recurrence was seen in 0.48% of
      patients (8/1653 sides), all of whom were male (P=0.01: male versus female). On
      multivariate analysis, age less than 1year was the only risk factor for
      recurrence in male patients (hazard ratio: 4.54, 95% CI: 1.07-19.25, P=0.04).
      CMIH was seen in 0.22% of the patients (3/1382), again only in male patients
      (P=0.12: male versus female). As a result of intraoperative observation, 44.6% of
      patients were confirmed to have an asymptomatic contralateral PPV and underwent
      prophylactic LPEC. Female, age 1year or older, right side, and surgeon's
      experience were identified as factors associated with asymptomatic contralateral
      PPV. CONCLUSIONS: To prevent recurrence, surgeons need to be careful when
      operating on young male patients. Whereas no specific factor could be identified
      as a risk factor for CMIH, some factors associated with asymptomatic PPV were
      identified. Further study and discussion will be needed to identify correlations
      between CMIH and these factors for PPV. LEVEL OF EVIDENCE: Level III.

PMID- 27894762
TI  - Bilateral congenital diaphragmatic hernia: prognostic evaluation of a large
      international cohort.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is a lethal birth defect, which
      occurs in 1:2000-3000 live births. Bilateral CDH is a rare form (1%), with a high
      mortality. This study presents the outcomes of the largest cohort of bilateral
      CDH patients. METHODS: The records of patients with bilateral CDH from the
      Congenital Diaphragmatic Hernia Registry born between 1995 and 2015 were
      retrospectively analyzed to identify parameters associated with mortality.
      RESULTS: Eighty patients with a bilateral CDH were identified. Overall mortality
      was 74% (n=59). Apgar scores at 1 and 5min were statistically lower in the non
      survivors compared to the survivors (median 3.0 and 5.0, versus 6.5 and 8.0,
      respectively, p<0.001). All survivors were repaired (n=21), compared to 22% of
      the non-survivors (n=17). The type of repair was equally divided in the survivors
      (52% primary versus 48% patch), while non-survivors were mainly patch repaired
      (82% versus 12%). Nineteen were treated with extracorporeal membrane oxygenation
      (ECMO) (24%), only three of them survived. When calculating the risk on mortality
      for the patients who lived until repair, ECMO had an adjusted odds ratio for
      mortality of 10.8 (95% CI: 2.0-57.7) and patch repair 5.2 (95% CI: 0.8-34.9).
      CONCLUSIONS: The treatment of bilateral CDH patients remains challenging with a
      high mortality rate. Lower Apgar-scores, ECMO (probably as a surrogate for the
      severity of disease), and patch repair were negatively associated with outcome.
      LEVEL OF EVIDENCE: Level IV study.

PMID- 27894763
TI  - Extended spectrum beta lactamase (ESBL) producing bacteria urinary tract
      infections and complex pediatric urology.
AB  - AIM OF THE STUDY: Extended spectrum beta lactamase (ESBL) producing bacteria are
      resistant to most beta-lactam antibiotics including third-generation
      cephalosporins, quinolones and aminoglycosides. This resistance is plasmid-borne
      and can spread between species. Management of ESBL is challenging in children
      with recurrent urinary tract infections (UTIs) and complex urological
      abnormalities. We aim to quantify the risk in children and specifically in
      urological patients. METHODS: Retrospective review of a microbiology database
      (April 2014 to November 2015). This identified urine isolates, pyuria, ESBL
      growth and patient demographics. Data analysis was by Chi square, Mann-Whitney U
      test and ANOVA. A P value of <0.05 was taken as significant. MAIN RESULTS:
      Analysis of 9418 urine samples showed 2619 with pure isolates, of which 1577 had
      pyuria (>10*106 WC/L). 136 urine cultures (n=79 patients) grew purely ESBL.
      Overall, 5.2% of urine isolates were ESBL and 9.5% isolates with pyuria (>100*106
      WC/L) had ESBL, whereas only 22/1032 (2.1%) with no pyuria, (P<0.0001). Urology
      patients had 86/136 (63%) ESBL positive cultures. These represented 86/315 (27%)
      of all positive cultures for urology patients vs. 50/2267 (2.2%) for all other
      specialties (P<0.0001). Potential ESBL transmission between organisms occurred in
      3 (all on prophylactic antibiotics). Over the study period, there was no
      significant rise of the monthly incidence between 2014 and 2015 (ANOVA P=0.1).
      CONCLUSION: This study is the first to document the incidence of ESBL in children
      (5%), and estimate the frequency of possible plasmid transmission between
      bacterial species in children. This quantifies the risk of ESBL, especially to
      urology patients, and mandates better antibiotic stewardship. LEVEL OF EVIDENCE:
      Level IIc.

PMID- 27894765
TI  - Outcome in adults with anorectal malformations in relation to modern
      classification - Which patients do we need to follow beyond childhood?
AB  - BACKGROUND/PURPOSE: Knowledge about the functional outcome in adults with
      anorectal malformations is essential to organize structured transition to adult
      care for this patient group. The aim of this study was to investigate the
      functional outcome and quality of life in adults with anorectal malformations
      characterized according to the Krickenbeck classification. METHODS: Of 256
      patients diagnosed with anorectal malformations at our institution in 1961-1993,
      203 patients could be traced and were invited to participate in the study. One
      hundred and thirty-six patients replied (67%) and were compared with one hundred
      and thirty-six population based sex and age-matched controls. Patients and
      controls were evaluated with both a validated questionnaire as well as a study
      specific questionnaire to assess bowel function. SF-36 was used for quality of
      life. Outcome in nine incontinence-related parameters, 10 constipation-related, 6
      urogenital function-related, and 13 quality of life parameters were assessed in
      the patients and compared to the outcome of controls as well as to the type of
      anorectal malformations according to the Krickenbeck classification. RESULTS: The
      ARM-patients had an inferior outcome (P<0.05) for all incontinence parameters, 8
      of 10 parameters for constipation, 2 of 6 for urogenital function and 7 of 13
      quality of life parameters. Patients with rectobulbar and vestibular fistulas had
      the worst statistical outcome but patients with cloaca and rectoprostatic/bladder
      neck fistula had worse outcome in absolute numbers. Forty-four patients (32%)
      reported incontinence of stool at least once a week and 16 (12%) had a permanent
      colostomy. CONCLUSIONS: The functional outcome and quality of life in adults with
      anorectal malformations are closely related to the type of malformation. A large
      proportion of the patients have persistent fecal incontinence, constipation and
      sexual problems that have a negative influence on their quality of life.
      Structured multidisciplinary follow-up of adults with anorectal malformations by
      pediatric and colorectal surgeons, as well as urologists and gynecologists is
      therefore advocated.

PMID- 27894764
TI  - Thoracoscopic bilateral T3 sympathectomy for primary focal hyperhidrosis in
      children.
AB  - AIM OF THE STUDY: Present our experience in the surgical treatment of primary
      focal hyperhidrosis of the hands by thoracoscopic bilateral T3 sympathectomy in
      pediatric patients. METHODS: Retrospective chart review of all patients operated
      between 2013 and 2015. RESULTS: We operated and included in the study 28
      patients, 22 females and 6 males. Mean age was 14 (6-21) years. All patients had
      previously tried at least one form of medical therapy with no success. All
      patients were extensively counseled regarding the potential side effects of the
      sympathectomy. The operations were done in supine position with the arms
      extended. All patients were intubated with a double-lumen endotracheal tube for
      sequential lung isolation. We used a 5-mm port for the scope and a 3-mm port for
      the instruments, both placed in the axilla. The third rib was identified by
      fluoroscopy. The sympathectomy was done with monopolar cautery. Mean operative
      time was 43 (25-71) minutes. No chest tubes were used. The incidence of
      intraoperative or postoperative complications was zero. All patients were
      discharged within the first 24 postoperative hours. All patients achieved
      immediate complete postoperative resolution of the palmar hyperhidrosis,
      sustained in all cases at a median follow-up of 17 (2-34) months. The mean
      preoperative quality of life score (based on a multifunctional self-assessment
      questionnaire) was 41/100, whereas after the operation, it was 92/100. Only 1
      patient developed temporary compensatory sweating. All patients were satisfied
      with the result of the operation. CONCLUSION: Thoracoscopic bilateral T3
      sympathectomy is a safe and effective treatment for children and adolescents with
      primary focal hyperhidrosis of the hands who failed medical management and have a
      very low rate of compensatory sweating. LEVEL OF EVIDENCE: IV.

PMID- 27894766
TI  - Risk and relevance of open lung biopsy in pediatric ECMO patients: the Dutch
      experience.
AB  - BACKGROUND: Open lung biopsy can help differentiate between reversible and
      irreversible lung disease and may guide therapy. To assess the risk-benefit ratio
      of this procedure in pediatric extracorporeal membrane oxygenation (ECMO)
      patients, we reviewed data of all patients who underwent an open lung biopsy
      during ECMO in one of the two pediatric ECMO centers in a nationwide study in the
      Netherlands. RESULTS: In nineteen neonatal and six pediatric patients (0
      15.5years), twenty-five open lung biopsies were performed during the study
      period. In 13 patients (52%), a classifying diagnosis of underlying lung disease
      could be made. In another nine patients (36%), specific pathological
      abnormalities were described. In three patients (12%), only nonspecific
      abnormalities were described. The histological results led to withdrawal of ECMO
      treatment in 6 neonates with alveolar capillary dysplasia/misalignment of
      pulmonary veins (24%) and in another 6 patients, corticosteroids were started
      (24%). All patients survived the biopsy procedure. Hemorrhagic complications were
      rare. CONCLUSION: An open lung biopsy during an ECMO run in neonates and children
      is a safe procedure with a minimum risk for blood loss and biopsy-related death.
      It can be very useful in diagnosing the underlying pathology and can guide
      cessation of ECMO treatment and thereby avoid continuation of futile treatment,
      especially in neonatal patients. LEVEL OF EVIDENCE: III. TYPE OF STUDY:
      Diagnostic study.

PMID- 27894767
TI  - Paratesticular rhabdomyosarcoma: Importance of initial therapy.
AB  - PURPOSE: To evaluate factors associated with progression-free and disease
      specific survival in patients with paratesticular rhabdomyosarcoma, we performed
      a cohort study. Also, since many patients present to our institution after
      initial therapy, we analyzed the effects of salvage therapy for scrotal
      violation. PATIENTS AND METHODS: We retrospectively reviewed the records of all
      consecutive patients with histologically confirmed paratesticular
      rhabdomyosarcoma treated at our institution between 1978 and 2015. Fifty-one
      patients were initially identified, but two with incomplete data were excluded
      from analysis. Variables evaluated for correlation with survival were TNM
      staging, Children's Oncology Group Soft Tissue Sarcoma pretreatment staging,
      margins at initial resection, presence of scrotal violation, hemiscrotectomy
      and/or scrotal radiation. The log-rank test was used to compare survival
      distributions. RESULTS: For the analytic cohort of 49 patients, the median age
      and follow-up were 15.7years (95% CI: 14.2-17.5, range: 0.8-25.1years) and
      6.9years (95% CI: 4.4-9.0, range 0.2-37.5years), respectively. The 5-year overall
      disease-specific survival was 78.7% (95% CI: 67.7%-91.4%) and the progression
      free survival was 66.9% (95% CI: 54.8%-81.6%). Median time to recurrence was
      0.9years (95% CI: 0.7-0.9, range 0.1-6.2years). Scrotal violation occurred in 41%
      (n=20) and tripled the risk of recurrence for patients not appropriately treated
      with either hemiscrotectomy or scrotal radiation therapy (RR=3.0, 95% CI: 1.16
      7.73). CONCLUSIONS: The strongest predictors of disease-specific survival were
      nodal status and distant metastasis at diagnosis. Scrotal violation remains a
      problem in paratesticular rhabdomyosarcoma and is a predictor of disease
      progression unless adequately treated. The risk of progression could be reduced
      with appropriate initial resection. LEVEL OF EVIDENCE: Level IV; retrospective
      study with no comparison group.

PMID- 27894768
TI  - Total esophagogastric dissociation: single center experience.
AB  - Aim: Fundoplication fails in approximately 20% of children with severe
      neurodisability. We aimed to evaluate total esophagogastric dissociation (TOGD)
      as a primary procedure and as a 'rescue' procedure for severely neurologically
      impaired children with significant swallowing discoordination and
      gastroesophageal reflux disease. Methods: Casenotes of 40 children with severe
      neurodisability who underwent TOGD between 2005 and 2015 were retrospectively
      reviewed. Of these, 33 were primary procedures and 7 were 'rescue' procedures
      following failed fundoplication. Results: Median age at surgery was 3 years 7
      months (range 1 month to 13 years 11 months). Preoperatively, all children had
      symptoms of regurgitation, retching or vomiting and 70% of children had an unsafe
      swallow. There were 5 early complications related to surgery in 4 children
      requiring surgical intervention. One child died following relaparotomy for
      esophagojejunal anastomotic breakdown because of multiorgan failure. Gastrostomy
      feeding was established by a median of 6 days (range 2 to 25 days) and median
      hospital stay was 10 days (range 4 to 280 days). There were 5 late complications.
      Median follow-up was 13 months (range 1 month to 8 years 4 months). All children
      have had resolution of gastroesophageal reflux. Thirteen percent of children
      experience bloating or pain on feeding and 26% of children experience retching
      unrelated to gastroesophageal reflux. There were 8 late deaths unrelated to
      surgery. Conclusion: TOGD should be considered as a primary and definitive
      procedure in selected severely neurodisabled children who are at higher risk of
      failure of fundoplication, recurrent aspiration and a reduced quality of life.

PMID- 27894769
TI  - Identification of molecular species of monoalkyldiacylglycerol from the squid
      Berryteuthis magister using liquid chromatography-APCI high-resolution mass
      spectrometry.
AB  - Monoalkyldiacylglycerol (MADAG) is an important lipid class in mollusks, corals,
      starfishes, and some species of zooplankton. Up to 80% of liver oils of squids
      and sharks are comprised of MADAG. Except for one fish species, there are no data
      on the composition of MADAG molecular species of marine organisms. The molecular
      species of MADAG obtained from digestive glands of the deep-sea squid
      Berryteuthis magister were identified. High-performance liquid chromatography
      (HPLC) and tandem high-resolution mass spectrometry (HRMS) with atmospheric
      pressure chemical ionization (APCI) were applied. The mass spectra of each
      molecular species contained positive quasi-molecular ion [M+H]+ with fragment
      ions [M-R'CO2]+, [M-R''CO2]+, and [M-OR''']+, as well as negative cluster ion
      [M+2H2OH]- without fragments. The exact masses of the negative ions allowed
      determination of the molecular formulas and the number of double bonds; the
      positive fragment ions were used to determine the location of acyl and alkyl
      groups in MADAG molecules. Ninety molecular species of MADAG were revealed. The
      regiospecific composition was identified for 72 individual molecular species.
      Eleven pairs of positional isomers of acyl groups were found. Four molecular ions
      were produced by a mixture of acyl/alkyl isomers. Most of molecular species
      contained 16:0e or 18:1e alkyl groups in the sn-1 position, whereas
      polyunsaturated fatty acids mainly esterified the sn-2 position of MADAG from B.
      magister. These structural features are supposed to be characteristic for
      biologically active MADAG.

PMID- 27894770
TI  - Activity-based targeting of secretory phospholipase A2 enzymes: A fatty-acid
      binding-protein assisted approach.
AB  - Syntheses and enzymological characterization of fluorogenic substrate probes
      targeting secretory phospholipase A2 (sPLA2) for detection and quantitative
      assays are presented. Three fluorogenic phosphatidylcholine analogs PC-1, PC-2,
      and PC-3 each containing the duo of 7-mercapto-4-methyl-coumarin fluorophore and
      2,4-dinitroanaline quencher on either tail were synthesized from (R)-3-amino-1,2
      propanediol and R-(-)-2,2-dimethyl-1,3-dioxolane-4-methanol. These small reporter
      groups are advantageous in preserving natural membrane integrity. Phosphocholine
      was incorporated into the sn-3 position of the glycerol backbone. Acyl amino
      group at the sn-1 position in PC-1 and PC-2 is meant to block sPLA1. The sn-1 and
      sn-2 positions of the glycerol backbone in PC-1 have a quencher terminated 12
      carbon chain and fluorophore terminated 11-carbon chain respectively. PC-2 has a
      quencher terminated 3-carbon chain at the sn-2 and chain terminating fluorescent
      reporter at the sn-1 positions. PC-3 resembles PC-1 except for an ester instead
      of amide at the sn-1 position, because of which it is more similar to natural
      phospholipids than PC-1. It was designed to elucidate the effect of replacing the
      ester group with amide by comparing its hydrolysis rate with that of PC-1. Design
      principles apply to synthesis of other labeled phospholipids. Enzymological
      characterization using bee-venom sPLA2 was performed by a fatty-acid-binding
      protein fluorescence assay and by pH-Stat method in which the amount of fatty
      acid released by hydrolysis is given by the amount of base required to maintain a
      constant pH of 8.0. Hydrolytic activity toward PC-1 and PC-3 were each about
      238+/-25MUmol/mg/min and 537MUmol/mg/min on unmodified phospholipid. Ester to
      amide change did not affect hydrolysis rates. Activity toward PC-2 was about 45
      MUmol/mg/min. PC-1 and PC-3 show potential for targeted real-time
      spectrophotometric assay of sPLA2.

PMID- 27894771
TI  - Radiation-induced DNA-protein cross-links: Mechanisms and biological
      significance.
AB  - Ionizing radiation produces various DNA lesions such as base damage, DNA single
      strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross
      links (DPCs). Of these, the biological significance of DPCs remains elusive. In
      this article, we focus on radiation-induced DPCs and review the current
      understanding of their induction, properties, repair, and biological
      consequences. When cells are irradiated, the formation of base damage, SSBs, and
      DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted
      in the absence of oxygen, suggesting their importance in hypoxic cells, such as
      those present in tumors. DNA and protein radicals generated by hydroxyl radicals
      (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can
      also be formed from guanine radical cations generated by the direct effect.
      Actin, histones, and other proteins have been identified as cross-linked
      proteins. Also, covalent linkages between DNA and protein constituents such as
      thymine-lysine and guanine-lysine have been identified and their structures are
      proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic
      manner, consisting of fast and slow components. The half-time for the fast
      component is 20min-2h and that for the slow component is 2-70h. Notably,
      radiation-induced DPCs are repaired more slowly than DSBs. Homologous
      recombination plays a pivotal role in the repair of radiation-induced DPCs as
      well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC
      protease was reported, wherein the resulting DNA-peptide cross-links were
      bypassed by translesion synthesis. The replication and transcription of DPC
      bearing reporter plasmids are inhibited in cells, suggesting that DPCs are
      potentially lethal lesions. However, whether DPCs are mutagenic and induce gross
      chromosomal alterations remains to be determined.

PMID- 27894772
TI  - The Syndrome of Heart Failure With Preserved Systolic Function.

PMID- 27894773
TI  - Cryoablation for Atrial Fibrillation: A Useful Technique Beyond Paroxysmal Forms
      of Arrhythmia?

PMID- 27894774
TI  - Evaluation of HAS-BLED and ORBIT Bleeding Risk Scores in Nonvalvular Atrial
      Fibrillation Patients Receiving Oral Anticoagulants. Response.

PMID- 27894775
TI  - Synthesis, characterization and biological studies of Schiff bases derived from
      heterocyclic moiety.
AB  - Some new Schiff bases (H1-H7) have been synthesized by the condensation of 2
      aminophenol, 2-amino-4-nitrophenol, 2-amino-4-methylphenol, 2-amino benzimidazole
      with thiophene-2-carboxaldehyde and pyrrole-2-carboxaldehyde. The structures of
      newly synthesized compounds were characterized by elemental analysis, FT-IR, 1H
      NMR, UV-VIS, and single crystal X-ray crystallography. The in vitro antibacterial
      activity of the synthesized compounds has been tested against Salmonella typhi,
      Bacillus coagulans, Bacillus pumills, Escherichia coli, Bacillus circulans,
      Pseudomonas, Clostridium and Klebsilla pneumonia by disk diffusion method. The
      quantitative antimicrobial activity of the test compounds was evaluated using
      Resazurin based Microtiter Dilution Assay. Ampicillin was used as standard
      antibiotics. Schiff bases individually exhibited varying degrees of inhibitory
      effects on the growth of the tested bacterial species. The antioxidant activity
      of the synthesized compounds was determined by the 1,1-diphenyl-2
      picrylhydrazyl(DPPH) method. IC50 value of synthesized Schiff bases were
      calculated and compared with standard BHA.

PMID- 27894776
TI  - Design, synthesis, cyclooxygenase inhibition and biological evaluation of new
      1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing
      amino/methanesulfonyl pharmacophore.
AB  - A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole 10a-l was designed and
      synthesized via cyclization of chalcones 8a-f with 4
      amino/methanesulfonylphenylhydrazine hydrochloride 9a-b. All the synthesized
      compounds were evaluated for their cyclooxygenase (COX) inhibition, anti
      inflammatory activity, ulcerogenic liability and analgesic activity. All
      compounds were more COX-2 inhibitors than COX-1. While most compounds showed good
      anti-inflammatory activity, the trimethoxy derivatives (10a, 10b, 10g and 10h)
      were the most potent derivatives (ED50=55.78, 53.99, 67.65 and 69.20MUmol/kg
      respectively) in comparison with celecoxib (ED50=82.15MUmol/kg). Compounds 10a,
      10b, 10g and 10h (ulcer index=2.68, 1.20, 2.63 and 2.66 respectively) showed less
      ulceration effect than celecoxib (ulcer index=2.90). Also, Compounds 10a, 10b,
      10g and 10h showed analgesic activity higher than celecoxib and comparable to
      that of ibuprofen. In addition, molecular docking studies were performed for
      compounds 10a, 10b, 10g and 10h and the results were in agreement with that
      obtained from the in vitro COX inhibition assays.

PMID- 27894777
TI  - Efficacy of Long-Acting Octreotide on Reducing Mucus Production in Patients With
      Ileal Neobladder.
AB  - PURPOSE: To evaluate the efficacy of long-acting-release octreotide (trade name
      Sandostatin) on decreasing mucus secretion, thus reducing catheter obstruction
      after radical cystectomy and orthotopic reconstruction. PATIENTS AND METHODS: In
      this double-blind, placebo-controlled study, we treated 73 cases of radical
      cystectomy between the years 2008 and 2014; 65 were deemed eligible for the
      study. Cases were randomly divided into 2 groups. Group A (n = 32) received 2
      doses of 20 mg intramuscular long-acting-release octreotide 4 weeks before and on
      the day of surgery, while group B (n = 33) received placebo. Catheter irrigation
      was only performed when there was an obstruction due to a mucus plug. The need
      for catheter irrigation and the volume of mucus produced by the neobladder were
      evaluated and compared between the 2 groups. RESULTS: The average number of
      neobladder irrigations required to treat mucus plugs was 2.3 +/- 1.5 in group A
      and 9.5 +/- 4.3 in group B (P < .001) before hospital discharge. This number
      changed to 2.5 +/- 1.5 versus 11.4 +/- 2.7 in groups A and B, respectively (P <
      .001), after discharge from the hospital. The 24-hour mucus production at the end
      of the first week was 5.4 +/- 2.7 mL versus 21.5 +/- 5.6 mL in groups A and B,
      respectively (P < .001). At the end of the third week, this amount changed to 5.5
      +/- 2.3 mL versus 21.8 +/- 5.6 mL in groups A and B, respectively (P < .001).
      CONCLUSION: Two injections of long-acting-release octreotide can dramatically
      reduce mucus production and hence catheter obstruction due to mucus plugs after
      radical cystectomy and orthotopic reconstruction.

PMID- 27894778
TI  - Stem cells in psoriasis.
AB  - Psoriasis is a complex chronic relapsing inflammatory disease. Although the exact
      mechanism remains unknown, it is commonly accepted that the development of
      psoriasis is a result of multi-system interactions among the epidermis, dermis,
      blood vessels, immune system, neuroendocrine system, metabolic system, and
      hematopoietic system. Many cell types have been confirmed to participate in the
      pathogenesis of psoriasis. Here, we review the stem cell abnormalities related to
      psoriasis that have been investigated recently.

PMID- 27894780
TI  - Antibody-free detection of infectious bacteria using quantum dots-based barcode
      assay.
AB  - Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Klebsiella
      pneumoniae are the most representative bacteria causing infectious diseases. Due
      to the increased application of antibiotics, the bacterial resistance is growing
      causing severe complications. Therefore, a sensitive determination of these
      pathogens is crucial for effective treatment. The aim of this study was to design
      an effective method for multiplex detection of Staphylococcus aureus, methicillin
      resistant Staphylococcus aureus and Klebsiella pneumoniae taking advantage from
      properties of magnetic particles as well as fluorescent nanoparticles (quantum
      dots). The method was able to detect as low concentrations of bacteria as 102
      CFU/mL using the bacteria-specific genes (fnbA, mecA and wcaG).

PMID- 27894779
TI  - Chrysin cocrystals: Characterization and evaluation.
AB  - Solvent free mechanochemical approach is utilized to synthesise new cocrystals of
      chrysin using supramolecular chemistry based upon reliable synthons. Chrysin, a
      flavone nutraceutical with wide range of beneficial effects has critically low
      bioavailability on account of its poor aqueous solubility and consequently poor
      absorption from the gastrointestinal tract. The present study focuses on this
      critical aspect and has exploited non covalent interactions to prepare its
      cocrystals with cytosine and thiamine hydrochloride. Various techniques were used
      for characterization including Differential Scanning Calorimetry (DSC), Fourier
      Transform Infrared Spectroscopy (FT-IR), Solid State NMR Spectroscopy (SSNMR) and
      Powder X-Ray Diffraction (PXRD). The molecules in the cocrystals crystallized in
      neutral forms and assembled in a molecular layer by means of hydrogen bonding
      which was confirmed by structural characterization. The cocrystals share a common
      supramolecular motif being the OH?Narom interaction, involving phenolic moiety of
      C7 functionality of the parent molecule. Approximately 3-4 fold increase in
      solubility and dissolution profile of cocrystals was observed which was further
      corroborated by improved in vitro and in vivo activities including antioxidant,
      antihaemolytic and anti-inflammatory thus, opening a new viable technique for the
      exploitation of useful phytonutrients.

PMID- 27894782
TI  - Transitioning EEG experiments away from the laboratory using a Raspberry Pi 2.
AB  - BACKGROUND: Electroencephalography (EEG) experiments are typically performed in
      controlled laboratory settings to minimise noise and produce reliable
      measurements. These controlled conditions also reduce the applicability of the
      obtained results to more varied environments and may limit their relevance to
      everyday situations. NEW METHOD: Advances in computer portability may increase
      the mobility and applicability of EEG results while decreasing costs. In this
      experiment we show that stimulus presentation using a Raspberry Pi 2 computer
      provides a low cost, reliable alternative to a traditional desktop PC in the
      administration of EEG experimental tasks. RESULTS: Significant and reliable MMN
      and P3 activity, typical event-related potentials (ERPs) associated with an
      auditory oddball paradigm, were measured while experiments were administered
      using the Raspberry Pi 2. While latency differences in ERP triggering were
      observed between systems, these differences reduced power only marginally, likely
      due to the reduced processing power of the Raspberry Pi 2. COMPARISON WITH
      EXISTING METHOD: An auditory oddball task administered using the Raspberry Pi 2
      produced similar ERPs to those derived from a desktop PC in a laboratory setting.
      Despite temporal differences and slight increases in trials needed for similar
      statistical power, the Raspberry Pi 2 can be used to design and present auditory
      experiments comparable to a PC. RESULTS: Our results show that the Raspberry Pi 2
      is a low cost alternative to the desktop PC when administering EEG experiments
      and, due to its small size and low power consumption, will enable mobile EEG
      experiments unconstrained by a traditional laboratory setting.

PMID- 27894781
TI  - Increased healthcare utilization costs following initiation of insulin treatment
      in type 2 diabetes: A long-term follow-up in clinical practice.
AB  - AIMS: To compare long-term changes in healthcare utilization and costs for type 2
      diabetes patients before and after insulin initiation, as well as healthcare
      costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. METHODS:
      Patients newly initiated on insulin (n=2823) were identified in primary health
      care records from 84 Swedish primary care centers, between 1999 to 2009. First,
      healthcare costs per patient were evaluated for primary care, hospitalizations
      and secondary outpatient care, before and up to seven years after insulin
      initiation. Second, patients prescribed insulin in second line were matched to
      patients prescribed NIAD in second line, and the healthcare costs of the matched
      groups were compared. RESULTS: The total mean annual healthcare cost increased
      from ?1656 per patient 2 years before insulin initiation to ?3814 seven years
      after insulin initiation. The total cumulative mean healthcare cost per patient
      at year 5 after second-line treatment was ?13,823 in the insulin group compared
      to ?9989 in the NIAD group. CONCLUSIONS: Initiation of insulin in type 2 diabetes
      patients was followed by increased healthcare costs. The increases in costs were
      larger than those seen in a matched patient population initiated on NIAD
      treatment in second-line.

PMID- 27894783
TI  - Comparison of speed-vacuum method and heat-drying method to measure brain water
      content of small brain samples.
AB  - BACKGROUND: A reliable measurement of brain water content (wet-to-dry ratio) is
      an important prerequisite for conducting research on mechanisms of brain edema
      formation. The conventionally used oven-drying method suffers from several
      limitations, especially in small samples. A technically demanding and time
      consuming alternative is freeze-drying. NEW METHOD: Centrifugal vacuum
      concentrators (e.g. SpeedVac/speed-vacuum drying) are a combination of vacuum
      drying and centrifugation, used to reduce the boiling temperature. These
      concentrators have the key advantages of improving the freeze-drying speed and
      maintaining the integrity of dried samples, thus, allowing e.g. DNA analyses. In
      the present study, we compared the heat-oven with speed-vacuum technique with
      regard to efficacy to remove moisture from water and brain samples and their
      effectiveness to distinguish treatment paradigms after experimental traumatic
      brain injury (TBI) caused by controlled cortical impact (CCI). RESULTS: Both
      techniques effectively removed water, the oven technique taking 24h and vacuum
      drying taking 48h. Vacuum-drying showed lower variations in small samples (30
      45mg) and was suitable for genomic analysis as exemplified by sex genotyping. The
      effect of sodium bicarbonate (NaBic8.4%) on brain edema formation after CCI was
      investigated in small samples (2*1mm). Only vacuum-drying showed low variation
      and significant improvement under NaBic8.4% treatment. COMPARISON WITH AN
      EXISTING METHOD: The receiver operating curves (ROC) analysis demonstrated that
      vacuum-drying (area under the curve (AUC):0.867-0.967) was superior to the
      conventional heat-drying method (AUC:0.367-0.567). CONCLUSIONS: The vacuum method
      is superior in terms of quantifying water content in small samples. In addition,
      vacuum-dried samples can also be used for subsequent analyses, e.g., PCR
      analysis.

PMID- 27894784
TI  - Hospital admission in older persons presenting with dizziness in the Emergency
      department.
AB  - One of the most frequent chief complaints among older persons presenting in the
      emergency department (ED) is dizziness. Nurses in the ambulance and in the ED
      play an important role in managing these patients. The challenge in the ED or
      ambulance is to, with limited diagnostic equipment; decide the correct level of
      care. The aim of this study was to identify factors that differed between those
      who were admitted to hospital and those who were not among older persons (65+)
      presenting in the ED with dizziness. The method was a retrospective journal
      audit. The sample consisted of persons (n=166) aged 65+ presenting in the ED with
      dizziness. Factors that were more frequent among those admitted to hospital were
      arriving with ambulance, priority and number of medications and high age. Forty
      percent of the dizzy patients were admitted to the hospital, 50% among those
      arriving with ambulance and 24% of the walk-in patients. Among the 166 patients
      included in the study because of dizziness, 64 different discharge diagnoses
      emerged, illustrating the complex nature of dizziness as a symptom. The results
      from this study can help the ambulance or ED nurse doing the first assessment
      with limited information and initiating the management, knowing what factors that
      are more frequent in older persons being admitted when presenting with dizziness.

PMID- 27894785
TI  - Simulating stable carbon and chlorine isotope ratios in dissolved chlorinated
      groundwater pollutants with BIOCHLOR-ISO.
AB  - BIOCHLOR is a well-known simple tool for evaluating the transport of dissolved
      chlorinated solvents in groundwater, ideal for rapid screening and teaching. This
      work extends the BIOCHLOR model for the calculation of stable isotope ratios of
      carbon and chlorine isotopes in chloroethenes. An exact solution for the three
      dimensional reactive transport of a chain of degrading compounds including
      sorption is provided in a spreadsheet and applied for modeling the transport of
      individual isotopes 12C, 13C, 35Cl, 37Cl from a constant source. The model can
      consider secondary isotope effects that can occur in the breaking of CCl bonds.
      The model is correctly reproducing results for delta13C and delta37Cl modeled by
      a previously published 1-D numerical model without secondary isotope effects, and
      is also reproducing results from a microcosm experiment with secondary chlorine
      isotope effects. Two applications of the model using field data from literature
      are further given and discussed. The new BIOCHLOR-ISO model is distributed as a
      spreadsheet (MS EXCEL) along with this publication.

PMID- 27894786
TI  - MR angiography can guide ED management of suspected acute aortic dissection.
AB  - BACKGROUND: Aortic dissection is typically evaluated with computed tomography
      angiography (CTA). However, the feasibility of using magnetic resonance
      angiography (MRA) in the ED is unclear. This study examined the indications and
      outcomes of MRA in suspected aortic dissection evaluation in the ED. METHODS: An
      IRB approved review identified patients who underwent MRA in the ED for acute
      thoracic aortic dissection from January 2010 to June 2016. Demographics, clinical
      assessment, CTA contraindications, outcomes, and ED disposition were analyzed.
      RESULTS: 50 MRAs were ordered for suspected thoracic aortic dissection. 21 (42%)
      for iodinated contrast allergy, 21 (42%) for renal insufficiency, 2 (4%) due to
      both, 2 (4%) to spare ionizing radiation, 2 (4%) for further work-up after CTA,
      and 2 (4%) due to prior contrast enhanced CT within 24h. Median ED arrival to MRA
      completion time was 311min. 42 studies were fully diagnostic; 7 were limited. One
      patient could not tolerate the examination. 49 MRAs were completed: 2 (4%)
      patients had acute dissection on MRA and 47 (96%) had negative exams. 17 (35%)
      received gadolinium. 18 (37%) patients were discharged home from the ED with a
      median length of stay of 643min. 2 (4%) were admitted for acute dissection seen
      on MRA and 29 (59%) for further evaluation. CONCLUSION: MRA has a clear role in
      the evaluation for acute thoracic aortic dissection in the ED in patients with
      contraindications to CTA, and can guide management and facilitate safe discharge
      to home.

PMID- 27894787
TI  - Safety and efficacy of liraglutide treatment in Japanese type 2 diabetes patients
      after acute myocardial infarction: A non-randomized interventional pilot trial.
AB  - BACKGROUND: Glucagon-like peptide 1 analogs are expected to exert a cardio
      protective action due to their effective glucose-lowering action and favorable
      potency on multifactorial metabolic pathways. However, the safety and
      tolerability of liraglutide treatment after a recent acute coronary syndrome
      (ACS) in Japanese patients with type 2 diabetes mellitus (T2DM) have yet to be
      fully established. METHODS: A total of eight T2DM patients were recruited within
      2 weeks after the onset of a ST-elevation myocardial infarction (STEMI) followed
      by successful percutaneous coronary intervention (PCI). The patients continued to
      receive liraglutide (up to 0.9mg once daily) for 24 weeks after the ACS combined
      with standard treatment such as a statin or beta-blocker. Changes in various
      metabolic parameters from pre-liraglutide treatment values were evaluated 24
      weeks after liraglutide treatment, and included glycemic and lipid profiles, and
      cardiac systolic and diastolic function assessed by cardiac ultrasonography.
      RESULTS: Twenty-four weeks of treatment with liraglutide reduced body weight
      (67.0+/-5.8kg to 62.0+/-7.8kg, p=0.003) and HbA1c level (6.6+/-0.5% to 5.9+/
      0.5%, p=0.006) and increased the level of 1,5-anhydroglucitol (12.8+/-6.9MUg/mL
      to 18.7+/-8.2MUg/mL, p=0.008) without development of hypoglycemia. There were no
      significant changes over 24 weeks in left ventricular systolic or diastolic
      function assessed by cardiac ultrasonography. No participant developed a major
      adverse cardiac event during the 24 weeks of liraglutide treatment, defined as
      cardiac death, new onset or recurrence of myocardial infarction, or needing
      target lesion revascularization. CONCLUSIONS: The present trial demonstrated that
      liraglutide treatment after onset of STEMI was well-tolerated in Japanese
      patients with T2DM over 24 weeks, and provided the first evidence to support
      clinical application of liraglutide treatment even just after ACS in Japanese
      high-risk T2DM patients.

PMID- 27894789
TI  - Cardiovascular event risk assessment in psoriasis patients treated with tumor
      necrosis factor-alpha inhibitors versus methotrexate.
AB  - BACKGROUND: Psoriasis is associated with increased risk for cardiovascular
      disease. OBJECTIVE: To compare major cardiovascular event risk in psoriasis
      patients receiving methotrexate or tumor necrosis factor-alpha inhibitor (TNFi)
      and to assess TNFi treatment duration impact on major cardiovascular event risk.
      METHODS: Adult psoriasis patients with >=2 TNFi or methotrexate prescriptions in
      the Truven MarketScan Databases (Q1 2000-Q3 2011) were classified as TNFi or
      methotrexate users. The index date for each of these drugs was the TNFi
      initiation date or a randomly selected methotrexate dispensing date,
      respectively. Cardiovascular event risks and cumulative TNFi effect were analyzed
      by using multivariate Cox proportional-hazards models. RESULTS: By 12 months,
      TNFi users (N = 9148) had fewer cardiovascular events than methotrexate users (N
      = 8581) (Kaplan-Meier rates: 1.45% vs 4.09%: P < .01). TNFi users had overall
      lower cardiovascular event hazards than methotrexate users (hazard ratio = 0.55;
      P < .01). Over 24 months' median follow-up, every 6 months of cumulative exposure
      to TNFis were associated with an 11% cardiovascular event risk reduction (P =
      .02). LIMITATIONS: Lack of clinical assessment measures. CONCLUSIONS: Psoriasis
      patients receiving TNFis had a lower major cardiovascular event risk compared to
      those receiving methotrexate. Cumulative exposure to TNFis was associated with a
      reduced risk for major cardiovascular events.

PMID- 27894790
TI  - Venous malformations of the head and neck: current concepts in management.
AB  - Low-flow venous malformations are congenital lesions and they are the third most
      common vascular anomaly in the head and neck. In this paper, the third in a
      series of three educational reviews, we discuss current trends in their
      management, and include a summary of common sclerosant agents used in their
      control.

PMID- 27894791
TI  - Intraoperative, surgeon-view, high-definition video broadcasting in intraoral
      surgery.

PMID- 27894788
TI  - Neurotoxic mechanisms of paclitaxel are local to the distal axon and independent
      of transport defects.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect
      of paclitaxel and other chemotherapeutic agents. Paclitaxel binds and stabilizes
      microtubules, but the cellular mechanisms that underlie paclitaxel's neurotoxic
      effects are not well understood. We therefore used primary cultures of adult
      murine dorsal root ganglion neurons, the cell type affected in patients, to
      examine leading hypotheses to explain paclitaxel neurotoxicity. We address the
      role of microtubule hyperstabilization and its downstream effects. Paclitaxel
      administered at 10-50nM for 1-3days induced retraction bulbs at the tips of axons
      and arrested axon growth without triggering axon fragmentation or cell death. By
      correlating the toxic effects and microtubule stabilizing activity of
      structurally different microtubule stabilizing compounds, we confirmed that
      microtubule hyperstabilization, rather than an off-target effect, is the likely
      primary cause of paclitaxel neurotoxicity. We examined potential downstream
      consequences of microtubule hyperstabilization and found that changes in levels
      of tubulin posttranslational modifications, although present after paclitaxel
      exposure, are not implicated in the paclitaxel neurotoxicity we observed in the
      cultures. Additionally, defects in axonal transport were not implicated as an
      early, causative mechanism of paclitaxel's toxic effects on dorsal root ganglion
      neurons. By using microfluidic chambers to selectively treat different parts of
      the axon with paclitaxel, we found that the distal axon was primarily vulnerable
      to paclitaxel, indicating that paclitaxel acts directly on the distal axon to
      induce degenerative effects. Together, our findings point to local effects of
      microtubule hyperstabilization on the distal-most portion of the axon as an early
      mediator of paclitaxel neurotoxicity. Because sensory neurons have a unique and
      ongoing requirement for distal growth in order to reinnervate the epidermis as it
      turns over, we propose that the ability of paclitaxel to arrest their growth
      accounts for the selective vulnerability of sensory neurons to paclitaxel
      neurotoxicity.

PMID- 27894793
TI  - A Quick Reference on Anion Gap and Strong Ion Gap.
AB  - Metabolic acid-base disorders are common in emergency and critically ill
      patients. Clinicians may have difficulty recognizing their presence when multiple
      acid-base derangements are present in a single patient simultaneously. The anion
      gap and the strong ion gap concepts are useful calculations to identify the
      components of complex metabolic acid-base associated to the presence of
      unmeasured anions. This article presents their definition, normal values,
      indications, limitations, and guidelines for interpretation of changes in the
      clinical setting.

PMID- 27894792
TI  - Pyruvate dehydrogenase-E1alpha deficiency presenting as recurrent acute proximal
      muscle weakness of upper and lower extremities in an 8-year-old boy.
AB  - The mitochondrial pyruvate dehydrogenase enzyme complex (PDHC) plays an important
      role in aerobic energy metabolism and acid-base equilibrium. PDHC contains of 5
      enzymes, 3 catalytic (E1, E2, E3) and 2 regulatory, as well as 3 cofactors and an
      additional protein (E3-binding protein) encoded by nuclear genes. The clinical
      presentation of PDHC deficiency ranges from fatal neonatal lactic acidosis to
      chronic neurologic dysfunction without lactic acidosis. Paroxysmal neurologic
      problems such as intermittent ataxia, episodic weakness, exercise-induced
      dystonia and recurrent demyelination may also be seen although they are rare.
      Here, we present an 8-year-old boy complaining of acute proximal muscle weakness
      of upper and lower extremities with normal mental status. He had a history of
      Guillain-Barre-like syndrome at the age of 2 years. Electrophysiologic studies
      showed sensorial polyneuropathy findings in the first attack and sensorimotor
      axonal polyneuropathy findings in the last attack. The genetic analysis revealed
      a previously reported hemizygote novel mutation of the PDHA1 gene
      (p.A353T/c.1057G > A), which encodes the E1alpha subunit of PDHC. Thiamine was
      ordered (15 mg/kg/day), dietary carbohydrates were restricted and clinical
      findings improved in a few weeks. This rare phenotype of PDHC deficiency is
      discussed.

PMID- 27894794
TI  - Fluid Therapy: Options and Rational Selection.
AB  - Administration of appropriate types and volumes of parenteral fluids is of
      paramount importance when treating sick and debilitated patients, especially
      those fighting critical illness. Fluid selection and accurate calculations must
      be performed logically and accurately to maximize positive outcomes. Knowledge of
      fluid types, as well as the complex relationship of the body's fluid
      compartments, helps clinicians develop rational fluid therapy plans for their
      patients.

PMID- 27894795
TI  - Histological parameters and alcohol abstinence determine long-term prognosis in
      patients with alcoholic liver disease.
AB  - BACKGROUND & AIMS: Few data exist on predictors of long-term prognosis in
      patients with alcoholic liver disease (ALD). Most studies have only assessed
      short-term prognosis in patients with advanced ALD. We aimed to assess the
      prognostic impact of clinical, biochemical and histological parameters on long
      term prognosis in patients with early/compensated and decompensated ALD. METHODS:
      Consecutive patients (n=192) with biopsy-proven liver disease due to alcohol
      abuse were analyzed retrospectively. Prognostic factors were evaluated in
      patients with early/compensated ALD (n=60) and in patients with decompensated ALD
      (clinical decompensation and/or bilirubin >3mg/dl at entry) (n=132). Factors that
      predict long-term survival were identified using Cox regression models. RESULTS:
      Liver-related mortality at 5years was 13% in early/compensated and 43% in
      decompensated ALD. In early/compensated ALD patients, long-term prognosis was
      determined by fibrosis stage, but not by clinical or biochemical variables.
      Severe fibrosis (F3/4) was present in 52% and had a major impact on 10-year
      mortality (F3/4: 45% vs. F0-2: 0%, p<0.001). In contrast, in decompensated
      patients, a combination of clinical features (sex), biochemical markers of liver
      failure (bilirubin, international normalized ratio [INR]), and histological
      features (pericellular fibrosis) predicted long-term survival. During follow-up,
      abstinence from alcohol was an important predictor of survival in both
      early/compensated and decompensated ALD. CONCLUSION: Fibrosis stage is the main
      predictor of long-term survival in patients with early/compensated ALD, while
      clinical, biochemical and histological parameters predict survival in patients
      with decompensated disease. Promoting abstinence may improve survival in patients
      with both early and advanced ALD. LAY SUMMARY: In this study, we evaluated long
      term outcome in 192 patients with alcoholic liver disease who underwent liver
      biopsy: 60 patients with early disease (no symptoms) and 132 patients with
      advanced disease (jaundice, complications of cirrhosis). Importantly, half of the
      patients with 'early' disease already had severe fibrosis or cirrhosis on liver
      histology and dismal outcome (45% mortality at 10years). Abstinence from alcohol
      improved the prognosis in both early and advanced stages of the disease.

PMID- 27894796
TI  - Cognitive challenges, aging, and neuromuscular fatigue.
AB  - Cognitive challenges, such as concurrent cognitive demands or prior cognitive
      fatigue, have shown to adversely impact neuromuscular fatigue, specifically in
      younger adults. Whether these relationships are similar for the aging population
      remains unclear. The aim of this study was to investigate the effects of
      different cognitive challenges on handgrip fatigue with aging. Ten younger (24.10
      (1.79) years) and ten older (75.90 (7.80) years) females attended three
      experimental conditions (control, i.e., exercise only, cognitive fatigue prior to
      exercise, and concurrent mental arithmetic during exercise) on different days.
      The exercise required them to grip intermittently at 30% maximum handgrip
      strength until voluntary exhaustion. Endurance time, strength loss, force
      steadiness, muscle activity, cardiovascular responses, perceptions of cognitive
      fatigue, mental demand, and discomfort were obtained. While endurance time was
      similar across age groups and conditions, older adults demonstrated ~35% reduced
      endurance than younger adults (46.96 (13.08) min.), but this was observed only in
      the concurrent cognitive demand condition. This was also accompanied with a
      decrease in force steadiness. No endurance differences between age groups were
      found during the control and cognitive fatigue condition. The findings indicate
      that the relationship between cognitive challenges and neuromuscular fatigue
      depends on age, the type of cognitive challenge imposed, and the type of exercise
      performed.

PMID- 27894798
TI  - Does drought in China show a significant decreasing trend from 1961 to 2009?
AB  - In recent decades, the occurrence and severity of drought in China has had
      devastating impact on social and economic development. The increase in drought
      has been attributed to global warming. We used the high-accuracy self-calibrating
      Palmer Drought Severity Index (scPDSI) to investigate the variation in drought in
      China between 1961 and 2009 using the Mann-Kendall (MK), continuous wavelet
      transform (CWT) and the rotated empirical orthogonal function (REOF) methods. We
      also analyzed the relationship between the rotated principal component time
      series (RPCs) and 74 circulation indices. The results revealed that: 1) all of
      China experienced a significant wet trend at annual and seasonal scale; an abrupt
      change in the drought pattern occurred around 1970 with a 2-8-year significant
      period; 2) eight major sub-climate regions were identified: Northwest China,
      Northeast-Inner Mongolia Plateau, Greater Khingan Range area, Northern Tibetan
      Plateau, Southern Tibetan Plateau, Central China, Huang-Huai-Hai Plain and
      Southeast China. Of these regions, the Southern Tibetan Plateau experienced a
      significant wet trend, but the Northeast-Inner Mongolia Plateau and Northern
      Tibetan Plateau became significantly drier. Using either annual or seasonal
      scales, Northwest China became significantly wetter and Central China became more
      arid. In addition, the period of each sub-climate region shared a significant 2-8
      year band; 3) the polar vortex exhibited dominant patterns that affected most
      areas of China. The Pacific Decadal Oscillation had a significant influence on
      drought evolution, especially for Northwest China and the Huang-Huai-Hai plain.
      Additionally, the El Nino-Southern Oscillation also affected drought evolution,
      and the Central China was impacted by the Indian Ocean Dipole.

PMID- 27894797
TI  - Roles of the serotonin 5-HT4 receptor in dendrite formation of the rat
      hippocampal neurons in vitro.
AB  - Serotonin (5-HT) is involved in various aspects of hippocampal development,
      although the specific roles of 5-HT receptors are poorly understood. We
      investigated the roles of 5-HT receptors in the dendrite formation of hippocampal
      neurons. We focused on the 5-HT4 receptor, which is coupled with Gs protein, and
      compared the effects with those of the Gi-coupled 5-HT1A receptor. Neurons from
      rat hippocampi at embryonic day 18 were dissociated and treated for 4 days with
      the 5-HT4 receptor agonist BIMU8 or the 5-HT1A receptor agonist 8-OH DPAT. The
      formation of primary dendrites and dendrite branching were promoted by BIMU8,
      whereas the dendrite branching was inhibited by 8-OH DPAT. BIMU8-induced
      promotion of dendrite formation was neutralized by concomitant treatment with the
      5-HT4 receptor antagonist, confirming the specific actions of the 5-HT4 receptor.
      We then examined the signaling mechanisms underlying the actions of the 5-HT4
      receptor by using a protein kinase A (PKA) inhibitor. The BIMU8-induced promotion
      of dendrite formation was reversed partially by the PKA inhibitor, suggesting
      involvement of PKA signaling downstream of the 5-HT4 receptor. Finally, we
      examined the contribution of brain-derived neurotrophic factor (BDNF) to the
      promotion of dendrite formation by BIMU8. Quantitative RT-PCR analysis showed
      that BIMU8 increased the BDNF mRNA expression and that treatment of cultured
      neurons with the TrkB antagonist reversed the BIMU8-induced increase in dendrite
      formation. In summary, the present study suggests a novel role for the 5-HT4
      receptor in facilitation of dendrite formation in which intracellular signaling
      of PKA and the BDNF-TrkB system may be involved.

PMID- 27894799
TI  - A microcosm experiment to determine the consequences of magnetic microparticles
      application on water quality and sediment phosphorus pools.
AB  - This study used microcosms to evaluate the effects of adding iron (Fe) magnetic
      microparticles (MPs) on water quality, focusing on P concentrations in the water
      column and sediment. Two treatments were considered for a constant 85:1
      MP:PMobile molar ratio: T-W, applying MPs on the surface water layer; and T-S,
      applying MPs on the sediment. MP addition reduced P concentrations in lake water
      and sediment, with both treatments producing a mean reduction of 68+/-6% in
      dissolved inorganic P concentration (DIP) over a 70-day oxic period and
      reductions of 80+/-8% (T-W) and 80+/-4% (T-S) over a 5-day anoxic period. MPs
      also decreased reactive silicate (Si) concentrations by around 50% in both
      periods, but dissolved organic carbon (DOC) was reduced by only 15% at 24h after
      MP addition. Despite the marked decrease in DIP concentration due to MP addition,
      there was no reduction in chlorophyll a (Chla), because post-treatment total P
      concentrations (>200MUgL-1vs. >700MUgL-1 before treatments) remained higher than
      required for changes in the biological community (0.05-0.1mgL-1). With T-S
      treatment, there was a reduction of 15% in P bound to Al oxides, clay minerals,
      and humic substances (P->NaOH) and of 12% in labile organic P (Org-PLabile)
      versus controls. P bound to humic substances (P->NaOH, Humic) was reduced by 11
      22% in both treatments. Finally, T-W rather than T-S treatments are recommended
      for future whole-lake applications to achieve more effective P removal from water
      and sediment and a higher percentage MP recovery.

PMID- 27894800
TI  - On persistent organic pollutants in Italy - From Seveso to the Stockholm
      Convention and beyond.

PMID- 27894801
TI  - Effects of the addition of nitrogen and sulfate on CH4 and CO2 emissions, soil,
      and pore water chemistry in a high marsh of the Min River estuary in southeastern
      China.
AB  - Exogenous nitrogen (N) and sulfate (SO42-), resulting from human activity, can
      strongly influence the emission of CH4 and CO2 from soil ecosystems. Studies have
      reported the effects of N and SO42- on CH4 and CO2 emissions from inland
      peatlands and paddies. However, very few studies have presented year-round data
      on the effects of the addition of N and SO42- on CH4 and CO2 emissions in
      estuarine marshes. The effects of the addition of N and SO42- on the emission of
      CH4 and CO2 were investigated in a Cyperus malaccensis marsh in the high tidal
      flat of the Min River estuary of southeastern China from September 2014 to August
      2015. Dissolved NH4Cl, KNO3, and K2SO4 were applied every month, in doses of
      24gN/SO42-m-2.yr-1. The emission of CH4 and CO2 showed distinct monthly and
      seasonal variations. Compared with the control, the addition of NH4Cl and
      NH4NO3+K2SO4 showed increases in CH4 fluxes (p<0.05), while the effects of the
      addition of KNO3 and K2SO4 on CH4 were minor (p>0.05). NH4Cl had a positive
      impact on CO2 emissions (p<0.01), while the addition of KNO3, K2SO4, and
      NH4NO3+K2SO4 had minor positive impacts, compared to the control (p>0.05).
      Correlation analysis found that soil sulfate concentration, nitrogen availability
      and enzyme activity were the dominant factors influencing CH4 and CO2 variation.
      Our findings suggest that CH4 and CO2 emissions were influenced more by ammonium
      than by nitrate. We propose that the suppressive effect of additional sulfate on
      CH4 production is insignificant, due to which the inhibition may be overestimated
      in the estuarine brackish marsh.

PMID- 27894802
TI  - Variation in the urban vegetation, surface temperature, air temperature nexus.
AB  - Our study examines the urban vegetation - air temperature (Ta) - land surface
      temperature (LST) nexus at micro- and regional-scales to better understand urban
      climate dynamics and the uncertainty in using satellite-based LST for
      characterizing Ta. While vegetated cooling has been repeatedly linked to
      reductions in urban LST, the effects of vegetation on Ta, the quantity often used
      to characterize urban heat islands and global warming, and on the interactions
      between LST and Ta are less well characterized. To address this need we
      quantified summer temporal and spatial variation in Ta through a network of 300
      air temperature sensors in three sub-regions of greater Los Angeles, CA, which
      spans a coastal to desert climate gradient. Additional sensors were placed within
      the inland sub-region at two heights (0.1m and 2m) within three groundcover
      types: bare soil, irrigated grass, and underneath citrus canopy. For the entire
      study region, we acquired new imagery data, which allowed calculation of the
      normalized difference vegetation index (NDVI) and LST. At the microscale, daytime
      Ta measured along a vertical gradient, ranged from 6 to 3 degrees C cooler at 0.1
      and 2m, underneath tall canopy compared to bare ground respectively. At the
      regional scale NDVI and LST were negatively correlated (p<0.001). Relationships
      between diel variation in Ta and daytime LST at the regional scale were
      progressively weaker moving away from the coast and were generally limited to
      evening and nighttime hours. Relationships between NDVI and Ta were stronger
      during nighttime hours, yet effectiveness of mid-day vegetated cooling increased
      substantially at the most arid region. The effectiveness of vegetated Ta cooling
      increased during heat waves throughout the region. Our findings suggest an
      important but complex role of vegetation on LST and Ta and that vegetation may
      provide a negative feedback to urban climate warming.

PMID- 27894803
TI  - Evaluating the impacts of the clean cities program.
AB  - The Department of Energy's Clean Cities program was created in 1993 to reduce
      petroleum usage in the transportation sector. The program promotes alternative
      fuels such as biofuels and fuel-saving strategies such as idle reduction and
      fleet management through coalitions of local government, non-profit, and private
      actors. Few studies have evaluated the impact of the program because of its
      complexity that include interrelated strategies of grants, education and training
      and diversity of participants. This paper uses a Difference-in-Differences (DiD)
      approach to evaluate the effectiveness of the program between 1990 and 2010. We
      quantify the effectiveness of the Clean Cities program by focusing on performance
      measures such as air quality, number of alternative fueling stations, private
      vehicle occupancy and transit ridership. We find that counties that participate
      in the program perform better on all these measures compared to counties that did
      not participate. Compared to the control group, counties in the Clean Cities
      program experienced a reduction in days with bad air quality (3.7%), a decrease
      in automobile commuters (2.9%), an overall increase in transit commuters (2.1%)
      and had greater numbers of new alternative fueling stations (12.9). The results
      suggest that the program is a qualified success.

PMID- 27894804
TI  - Human and veterinary pharmaceuticals in the marine environment including fish
      farms in Korea.
AB  - The occurrence trends and effects of 30 human and veterinary pharmaceuticals,
      including antibiotics, anthelmintics, anti-inflammatory drugs, and beta-blockers,
      in the marine environment, with a focus on seawater, sediment, cultured fish, and
      their feed collected from coastal and fish farm areas in the southern sea of
      Korea, were investigated. The concentrations of total pharmaceuticals in coastal
      area seawater (mean: 533ng/L) were higher than those in fish farm seawater (mean:
      300ng/L), while the opposite trend (coastal area: 136ng/gdrywt<fish farm area;
      195ng/gdrywt) was observed for sediment samples. Regarding cultured fish, the
      concentration of total pharmaceuticals in fish muscle (mean: 5.08ng/gwetwt) was
      lower than that in organs (mean: 14.1ng/gwetwt). However, not all compounds were
      present at higher concentrations in organs. Characteristic distribution patterns
      of pharmaceuticals were observed according to sample types and sampling sites
      based on the predominance of various antibiotics in fish farms (including
      cultured fish and feed) and the predominance of pharmaceuticals of terrestrial
      origin (human and livestock) in coastal areas. Pharmaceuticals used as fish
      drugs, such as sulfadiazine, erythromycin, and trimethoprim, were commonly
      detected in fish farm media (seawater, sediment, and cultured fish), which might
      contaminate fish farm media.

PMID- 27894805
TI  - Leaching behavior of veterinary antibiotics in animal manure-applied soils.
AB  - Agricultural fields worldwide are being contaminated by the escalating
      application of veterinary antibiotics (VAs) via animal manure and biosolids
      applied as fertilizers or of wastewater for irrigation, resulting in soil
      degradation and damage to the health of terrestrial environments. This paper
      describes a series of column studies investigating the leaching behavior of five
      VAs, tetracycline (TC), sulfamethazine (SMZ), norfloxacin (NOR), erythromycin
      (ERY) and chloramphenicol (CAP), under different simulated rainfall conditions
      that could occur in agricultural environments. Our aim was to explore the effects
      of acid rain and torrential rain on the leaching of different VAs and to
      determine their leaching behaviors along the soil profile. The results showed
      that acid rain accelerated the accumulation of VAs from animal manure in surface
      soil while long rainfall durations promoted the downward migration of VAs in
      soil. Under acid rain conditions, a higher concentration of VAs remained in the
      animal manure. More VAs were eluted to deeper soil layers and the leachate under
      extreme rainfall conditions. The leachability of VAs was higher in sandy soil
      than in clay or loamy soil. SMZ and ERY posed a higher risk to deeper soil layers
      and groundwater, while NOR and TC tended to persist in surface soil, which can be
      explained by their different physicochemical properties in soil. Moreover, the
      general trends from two model assessments and soil column measurements appeared
      to be in agreement. SMZ had a high leachability, while NOR tended to accumulate
      in soils. This study provided vital insight into the persistence mechanisms of
      VAs in terrestrial environments and their potential risks to soils and
      groundwater.

PMID- 27894807
TI  - Cytokine signaling in cancer: Novel players and pathways.
AB  - Cancer, like many others, is a disease due to dysfunction of cytokine-regulated
      networks. In this background, the 1st Aegean conference meeting focused on the
      Cytokine Signaling in Cancer was organized and held at Chania, Crete, Greece in
      May of 2015. A number of novel aspects of the cytokine signaling and their
      relevance to oncogenic processes were presented at that meeting. This special
      issue of Cytokine captures snap shots of this meeting in the form of reviews. In
      addition to these reviews, several other original research articles on the roles
      of cytokines and chemokines in various cancers are also present in this issue.

PMID- 27894808
TI  - Protective effect of betulinic acid on early atherosclerosis in diabetic
      apolipoprotein-E gene knockout mice.
AB  - Atherosclerosis, a chronic and progressive disease, is a leading cause of
      endothelial dysfunction, diabetes mellitus, hypertension, and
      hypercholesterolemia. Betulinic acid (BA), a pentacyclic triterpene, has been
      reported to have a variety of biological effects, including anti-inflammatory and
      immunomodulatory properties. This study was designed to determine whether BA
      could prevent atherosclerosis in diabetic apolipoprotein-E gene knockout (ApoE
      KO) mice. The mice were treated with BA for 12 weeks to examine its beneficial
      effects on atherosclerosis in ApoE KO mice. Male ApoE KO mice and age-matched
      control group mice (C57BL/6Jms) were used as experimental systems and their
      systolic blood pressure, insulin resistance, and vascular inflammation were
      measured. BA-treated ApoE KO mice showed lowered systolic blood pressure. The
      metabolic parameter showed that BA decreased blood urea nitrogen, triglyceride,
      and total cholesterol levels. Blood glucose, insulin, glucose tolerance results,
      and the homeostasis model assessment of insulin resistance (HOMA-IR) index were
      found to be better in BA-treated ApoE KO mice than untreated ApoE KO mice.
      Consistent with the change in lipid profiles, oil red O and H&E staining revealed
      that treatment with BA reduced atherosclerotic lesions such as roughened
      endothelial layers. BA ameliorated the reduction of endothelial nitric oxide
      synthase (eNOS) expression, leading to the inhibition of intracellular adhesion
      molecule 1 (ICAM-1) and endothelin 1 (ET-1) expression. These results suggest
      that BA may be useful in the treatment and prevention of early atherosclerosis
      via the attenuation of endothelial dysfunction in diabetic ApoE KO mice.

PMID- 27894806
TI  - Genetic divergence in the transcriptional engram of chronic alcohol abuse: A
      laser-capture RNA-seq study of the mouse mesocorticolimbic system.
AB  - Genetic factors that influence the transition from initial drinking to dependence
      remain enigmatic. Recent studies have leveraged chronic intermittent ethanol
      (CIE) paradigms to measure changes in brain gene expression in a single strain at
      0, 8, 72 h, and even 7 days following CIE. We extend these findings using LCM RNA
      seq to profile expression in 11 brain regions in two inbred strains - C57BL/6J
      (B6) and DBA/2J (D2) - 72 h following multiple cycles of ethanol self
      administration and CIE. Linear models identified differential expression based on
      treatment, region, strain, or interactions with treatment. Nearly 40% of genes
      showed a robust effect (FDR < 0.01) of region, and hippocampus CA1, cortex, bed
      nucleus stria terminalis, and nucleus accumbens core had the highest number of
      differentially expressed genes after treatment. Another 8% of differentially
      expressed genes demonstrated a robust effect of strain. As expected, based on
      similar studies in B6, treatment had a much smaller impact on expression; only 72
      genes (p < 0.01) are modulated by treatment (independent of region or strain).
      Strikingly, many more genes (415) show a strain-specific and largely opposite
      response to treatment and are enriched in processes related to RNA metabolism,
      transcription factor activity, and mitochondrial function. Over 3 times as many
      changes in gene expression were detected in D2 compared to B6, and weighted gene
      co-expression network analysis (WGCNA) module comparison identified more modules
      enriched for treatment effects in D2. Substantial strain differences exist in the
      temporal pattern of transcriptional neuroadaptation to CIE, and these may drive
      individual differences in risk of addiction following excessive alcohol
      consumption.

PMID- 27894809
TI  - Cyclic AMP (cAMP) confers drug resistance against DNA damaging agents via PKAIA
      in CML cells.
AB  - Cyclic adenosine monophosphate (cAMP) regulates many vital functions such as
      metabolism, proliferation, differentiation and death. Depending on cell types and
      stimulators, cAMP could either promote or attenuate cell death. cAMP signal can
      be transduced by protein kinase A (PKA) and/or exchange protein directly
      activated by cAMP (EPAC). In CML cells, cAMP may suppress their proliferation and
      enhance their differentiation. However, the role of cAMP on DNA damaging agent
      toxicity and the mechanism involved has not been studied. In this study, we
      studied the effect of cAMP on the sensitivity of CML cells to DNA damaging
      agents. We observed that forskolin (FSK) and dibutyryl-cAMP (DBcAMP) decreased
      cisplatin and etoposide-induced cell death in K562 cells. Moreover, PKA activator
      prevented K562 cells from DNA damaging agent-induced cell death while EPAC
      activator had no effect. Furthermore, we found that the PKA subtype, PKAIA, was
      involved in cAMP-attenuated resistance in K562 cells. Taken together, our results
      suggest that increased cAMP level confers CML cells to acquire a novel mechanism
      against DNA damaging agent toxicity via PKAIA. Thus, PKAIA inhibitor may be
      helpful in overcoming the resistance to DNA damaging agents in CML cells.

PMID- 27894810
TI  - Na+/Ca2+ exchanger 1 inhibition abolishes ischemic tolerance induced by ischemic
      preconditioning in different cardiac models.
AB  - Ca2+-handling disturbances play an important role in the genesis of myocardial
      ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) is a powerful
      strategy to induce tolerance against subsequent ischemic episodes. IPC signaling
      pathways may be triggered by Ca2+ ion. Since Na+/Ca2+ exchanger 1 (NCX1)
      participates in modulating intracellular Ca2+ homeostasis, here we further
      defined its role in I/R and investigated its potential involvement in IPC-induced
      cardioprotection. In isolated ventricular cardiomyocytes, perfused rat heart and
      H9c2 cardiomyoblasts, I/R produced a significant cell injury, assessed by
      measuring extracellular lactate dehydrogenase (LDH) and, for the whole heart,
      also by estimating myocardial infarct size area. Characterization of cell death
      revealed the involvement of apoptotic processes. Interestingly, I/R challenge
      induced NCX1 protein upregulation. In NCX1-transfected H9c2 cells, exchanger
      protein upregulation was accompanied by an increase in its reverse mode activity.
      The effects of I/R on extracellular LDH and infarct size area were drastically
      reduced by 1MUM SN-6, a selective NCX1 inhibitor. Moreover, SN-6 also prevented
      I/R-induced increase of NCX1 reverse-mode activity and protein upregulation.
      These results suggested a deleterious role of NCX1 in I/R-induced cell damage. In
      both isolated cardiomyocytes and perfused heart, IPC followed by I/R afforded
      cardioprotection, reducing extracellular LDH release and limiting ischemic area
      extent. Interestingly, NCX1 blockade (1MUM SN-6) completely abolished IPC
      protection against I/R, leading to exacerbation of cell injury, massive infarct
      size area and restoration of NCX1 protein expression. These findings suggest that
      NCX1 is deleterious in I/R, whereas it may be beneficial in promoting IPC-induced
      cardioprotection.

PMID- 27894811
TI  - Critical role of Toll-like receptors in pathophysiology of allergic asthma.
AB  - Allergic asthma is an airway disease, characterized by reversible
      bronchoconstriction, chronic inflammation of the airway, and thickness of smooth
      muscle in the respiratory tract. Asthma is orchestrated by an excessive Th2
      adaptive immune response, in which innate immunity plays a key role. Recently
      TLRs have received more and more attention as they are central to orchestrate the
      innate immune responses. TLRs are localized as integral membrane or intracellular
      glycoproteins with those on the cell surface sensing microbial antigens and the
      ones, localized in intracellular vesicles, sensing microbial nucleic acid
      species. Having recognized microbial antigens, TLRs conduct the immune response
      towards a pro- or anti-allergy response. As a double-edged sword, they could
      initiate either harmful or helpful responses by the immune system in case of
      allergic asthma. In the current review, we will describe the role of TLRs and
      their signaling pathways in allergic asthma.

PMID- 27894812
TI  - Enhanced legumain-recognition and NIR controlled released of cisplatin
      indocyanine nanosphere against gastric carcinoma.
AB  - Cisplatin-therapy has faced limitations in the gastric cancer therapy. To settle
      the bottleneck, enhanced specificity and controlled-release property are choosen.
      We synthesize cisplatin and indocyanine green (ICG) loaded PLGA-(DSPE-PEG2000)
      nanoparticles, which is abbreviated as CINPs. And we conjugate the Gly-Cys-Gly
      Ala-Ala-Asn-Leu (GCGAANL) heptapeptide upon the surface of CINPs, the product is
      abbreviated as ACINPs. ACINPs with nearly 110nm exhibit good monodispersity and
      size stability. The EE (efficiency of encapsulation) and LE (loading of
      encapsulation) of cisplatin loaded into ACINPs are optimized as 29.81% and 3.88%.
      MGC803 cells overexpressing the legumain and MKN28 cells, which negatively
      express the legumain as well as the normal stomach cells, are selected. In vitro
      studies have suggested ACINPs, compared with CINPs, could be recognized by MGC803
      cells and efficiently killed the cancer cells, while be harmless to MKN28 cells,
      which indicates the specificity and safety of ACINPs. Under irradiation of 808nm
      NIR irradiation, ICG loaded in ACINPs could rapidly transform the light to heat
      up to 60C. Nanoparticles compared with non-irraditaion group could be quickly
      disrupted and release the cisplatin which could enhance the controlled-release
      ability. Hence, the ACINPs exhibit great potential in avoiding the side effects
      and enhancing the therapy ability of cisplatin.

PMID- 27894813
TI  - Salicylic acid retention impairs aspirin reactivity in type 2 diabetes.
AB  - High on-aspirin platelet reactivity (HAPR) has been associated with compromised
      aspirin efficacy in patients with diabetes suffering from acute cardiovascular
      events, but the key mechanisms remain elusive. The objective of this study was to
      uncover the potential link between pathogenic accumulation of salicylic acid
      (SA), the major metabolite of aspirin, and HAPR in diabetic state. Aspirin failed
      to inhibit platelet CD62P expression and thromboxane (TX) B2/6-keto
      prostaglandin(PG)F1alpha ratio in a type 2 diabetes mellitus (T2DM) mice model,
      particularly in the female, which were unanimously accompanied by significantly
      higher plasma SA concentrations. Pre-administration with SA increased both
      platelet CD62P expression and TXB2/6-keto-PGF1alpha ratio in female T2DM mice,
      while pretreatment with NaHCO3 caused the opposite effect. On the in vitro human
      umbilical vein endothelial cells (HUVECs)-platelet interaction assay, SA
      suppressed inflammation-induced cyclooxygenase-2 upregulation on HUVECs and
      attenuated their inhibitory effect on platelet aggregation in a dose-dependent
      manner. The prolonged retention of SA in diabetes may be partially explained by
      the downregulation of various SA efflux transporters in the kidney and the
      decreased urine pH. Importantly, in female aspirin non-responsive patients, the
      trough plasma concentration of SA are markedly increased with T2DM treated with
      long-term aspirin, and TXB2/6-keto-PGF1alpha ratio and uric acid level in plasma
      are positively correlated with SA concentration. Our findings support that the
      accumulation of SA represents an important factor in causing HAPR in diabetes,
      and that targeting impaired SA excretion may become a novel intervention strategy
      to diabetes-associated HAPR.

PMID- 27894814
TI  - Tanshinone IIA induced cell death via miR30b-p53-PTPN11/SHP2 signaling pathway in
      human hepatocellular carcinoma cells.
AB  - Tanshinone IIA, a multi-pharmaceutical compound from traditional Chinese herb,
      has been reported to have anti-hepatocarcinomic (HCC) properties through cell
      death induction. Apart from the typical p53-dependent pathway, mechanisms of the
      anti-carcinogenic role of Tanshinone remain scarce. In an effort to explore the
      mechanism behind Tanshinone IIA, we detected the upstream of the p53 and the
      potential novel pathway. Tanshinone IIA dose-dependently initiated HepG2 cell
      apoptosis and cell cycle arrest at the G1 checkpoint. In the miR30 family, only
      the transcription of miR30b was downregulated by Tanshinone IIA, which
      subsequently upregulated both the genomic and protein levels of p53. Further, we
      screened that PTPN11 and Tp53 are the two critical genomes involved in the
      pharmacology of Tanshinone IIA. Building upon LASAGNA-search and kinetics binding
      assay, p53 was found to be a potential transcription factor for PTPN11.
      Concomitant with the expression of p53, Tanshinone IIA stimulated both PTPN11 and
      its encoded protein SHP2. Inhibition miR30b attenuated the Tanshinone IIA-induced
      cytotoxicity, level of p53 and PTPN11 in HepG2 cells. Finally, the apoptotic
      molecules such as Bax/Bcl2, cleavage caspase 3 and the cell cycle regulation
      factors including p21, cyclin D1, and CDK6 were changed by Tanshinone IIA.
      Several cytotoxic endpoints induced by Tanshinone IIA were also checked in Hep3B
      cells. This study confirmed that Tanshinone IIA may induce hepatoma cell death
      through the miR30b-p53- PTPN11/SHP2 pathway. With regard to the complicated
      tumorigenesis of HCC and the multi-targets of Tanshinone IIA, our results propose
      developing Tanshinone IIA for clinic therapy and the interference of HCC.

PMID- 27894816
TI  - Measuring the impact of alcohol-related disorders on quality of life through
      general population preferences.
AB  - OBJECTIVE: To estimate the intangible effects of alcohol misuse on the drinker's
      quality of life, based on general population preferences METHODS: The most
      important effects (dimensions) were identified by means of two focus groups
      conducted with patients and specialists. The levels of these dimensions were
      combined to yield different scenarios. A sample of 300 people taken from the
      general Spanish population evaluated a subset of these scenarios, selected by
      using a fractional factorial design. We used the probability lottery equivalent
      method to derive the utility score for the evaluated scenarios, and the random
      effects regression model to estimate the relative importance of each dimension
      and to derive the utility score for the rest of scenarios not directly evaluated.
      RESULTS: Four main dimensions were identified (family, physical health,
      psychological health and social) and divided into three levels of intensity. We
      found a wide variation in the utilities associated with the scenarios directly
      evaluated (ranging from 0.09 to 0.78). The dimensions with the greatest relative
      importance were physical health (36.4%) and family consequences (31.3%), followed
      by psychological (20.5%) and social consequences (11.8%). CONCLUSIONS: Our
      findings confirm the benefits of adopting a heterogeneous approach to measure the
      effects of alcohol misuse. The estimated utilities could have both clinical and
      economic applications.

PMID- 27894817
TI  - Training in Fetal-Neonatal Neurology: Principles to Guide Practice for Career
      Long Learning.

PMID- 27894819
TI  - New possible biomarkers for diagnosis of infections and diagnostic distinction
      between bacterial and viral infections in children.
AB  - Detailed information about patients with infections is required to ensure
      appropriate choice of treatment. Although white blood cell (WBC) counts, and C
      reactive protein (CRP) levels are useful diagnostic indicators of infections,
      more rapid and easily assayed indicator(s) could improve diagnosis. Moreover, it
      is of pivotal importance to distinguish bacteria or viruses as causative
      pathogens. Overall, TLR2 and TLR4 expression levels in neutrophils derived from
      individuals (n = 118) with bacterial (n = 37) and viral (n = 34) infections were
      higher than those in control samples (n = 47). Significant higher levels of TNF
      alpha in patients with both types of the infection were observed, and those of IL
      4, IL-8, IL-10, and IL-12 also were observed in the present study. Levels of IL
      2, IL-8, and IL-10 on day 1 post-viral infection were significantly higher than
      those on day 1 post-bacterial infection. Therefore, there is a possibility that
      IL-4, IL-8, IL-10, IL-12 and TNF-alpha might be biomarkers for infections, in
      addition to WBC counts and CRP levels, and that IL-2, IL-8 or IL-10 are
      potentially able to distinguish between bacterial and viral infections.

PMID- 27894815
TI  - The Histone Variant H3.3 in Transcriptional Regulation and Human Disease.
AB  - Histone proteins wrap around DNA to form nucleosomes, which further compact into
      the higher-order structure of chromatin. In addition to the canonical histones,
      there are also variant histones that often have pivotal roles in regulating
      chromatin dynamics and in the accessibility of the underlying DNA. H3.3 is the
      most common non-centromeric variant of histone H3 that differs from the canonical
      H3 by just 4-5 aa. Here, we discuss the current knowledge of H3.3 in
      transcriptional regulation and the recent discoveries and molecular mechanisms of
      H3.3 mutations in human cancer.

PMID- 27894820
TI  - Quantitative detection of periodontopathic bacteria in lower respiratory tract
      specimens by real-time PCR.
AB  - The presence of common periodontopathic bacteria, the Fusobacterium nucleatum
      periodonticum-simiae group, Prevotella intermedia, and Porphyromonas gingivalis
      was determined from respiratory tract specimens of bacterial pneumonia by real
      time PCR using universal and species-specific TaqMan probe/primer sets. 42
      patients with infectious pneumonia and 45 patients without infectious pneumonia
      were retrospectively enrolled in clinical studies. Periodontopathic bacterial DNA
      was found in 57.1% cases of infectious pneumonia and 31.1% cases of noninfectious
      pulmonary disease. However, the proportion of periodontopathic bacterial DNA did
      not differ between the two groups, and the presence or proportion of
      periodontopathic bacterial DNA was not related to any clinical index of
      pneumonia. Only two pneumonia cases consisted of >30% Fusobacterium DNA,
      suggesting that Fusobacterium was the causal pathogen in these cases. Our
      findings suggest that the periodontopathic bacteria rarely proliferate and be
      etiological pathogen in lower airway tract. However, further study is necessary,
      focusing on the pathogenicity of F. nucleatum in pulmonary infectious disease.

PMID- 27894821
TI  - Schizophrenia in mid-adulthood after prenatal exposure to the Chinese Famine of
      1959-1961.
AB  - Analyzing data from a large-scale, nationally representative sample, this study
      examines the association between prenatal exposure to the Chinese Famine (1959
      1961) and schizophrenia risk in mid-adulthood and its urban/rural-specific and
      gender-specific patterns. The results showed that the cohort conceived and born
      during the famine had a higher risk of schizophrenia in mid-adulthood than
      cohorts conceived and born before or after the famine. In addition, schizophrenia
      risk was higher for urban residents than for rural residents and higher for
      females than for males. Drawing on the psychiatric features of late-onset
      schizophrenia in mid-adulthood, we then offer some theoretical mechanisms to
      explain the cohort, urban/rural, and gender differences.

PMID- 27894818
TI  - Supt20 is required for development of the axial skeleton.
AB  - Somitogenesis and subsequent axial skeletal development is regulated by the
      interaction of pathways that determine the periodicity of somite formation,
      rostrocaudal somite polarity and segment identity. Here we use a hypomorphic
      mutant mouse line to demonstrate that Supt20 (Suppressor of Ty20) is required for
      development of the axial skeleton. Supt20 hypomorphs display fusions of the ribs
      and vertebrae at lower thoracic levels along with anterior homeotic
      transformation of L1 to T14. These defects are preceded by reduction of the
      rostral somite and posterior shifts in Hox gene expression. While cycling of
      Notch target genes in the posterior presomitic mesoderm (PSM) appeared normal,
      expression of Lfng was reduced. In the anterior PSM, Mesp2 expression levels and
      cycling were unaffected; yet, expression of downstream targets such as Lfng,
      Ripply2, Mesp1 and Dll3 in the prospective rostral somite was reduced accompanied
      by expansion of caudal somite markers such as EphrinB2 and Hes7. Supt20 interacts
      with the Gcn5-containing SAGA histone acetylation complex. Gcn5 hypomorphic
      mutant embryos show similar defects in axial skeletal development preceded by
      posterior shift of Hoxc8 and Hoxc9 gene expression. We demonstrate that Gcn5 and
      Supt20 hypomorphs show similar defects in rostral-caudal somite patterning
      potentially suggesting shared mechanisms.

PMID- 27894823
TI  - Development of fast neurotransmitter synapses: General principle and recent
      progress.

PMID- 27894824
TI  - Inhibitory effect of phloretin on alpha-glucosidase: Kinetics, interaction
      mechanism and molecular docking.
AB  - As the aglycone of phloridzin, phloretin belongs to dihydrochalcone with
      antioxidant, anti-inflammatory and antimicrobial activities. In this study,
      multispectroscopic techniques and molecular docking analysis were used to
      investigate the inhibitory activity and mechanisms of phloretin on alpha
      glucosidase. The results showed that phloretin reversibly inhibited alpha
      glucosidase in a mixed-type manner and the value of IC50 was 31.26MUgL-1. The
      intrinsic fluorescence of alpha-glucosidase was quenched by the interactions with
      phloretin through a static quenching mechanism and spontaneously formed phloretin
      alpha-glucosidase complex by the driving forces of van der Waals force and
      hydrogen bond. Atomic force microscope (AFM) studies and FT-IR measurements
      suggested that the interactions could change the micro-environments and
      conformation of the enzymes and the molecular docking analysis displayed the
      exact binding site of phloretin on alpha-glucosidase. These results indicated
      that phloretin is a strong alpha-glucosidase inhibitor, thus could be contribute
      to the improvement of diabetes mellitus.

PMID- 27894825
TI  - Designing chitosan-tripolyphosphate microparticles with desired size for specific
      pharmaceutical or forensic applications.
AB  - Chitosan (CS) is a natural cationic polymer obtained by the partial N
      deacetylation of chitin. Chitosan microparticles can be prepared by cross-linking
      with tripolyphosphate (TPP) via the ionic interaction between positively charged
      amino groups (CS) and negatively charged counter ions (TPP). This can be
      controlled by the charge density of CS and TPP, which depend on the pH and ionic
      strength of the solution. The purpose of this study is to investigate the
      combined effects of three independent variables (pH, ionic strength and CS:TPP
      ratio) on three important physico-chemical properties (viscosity, zeta potential
      and particle size) during the preparation of microparticles. CS:TPP
      microparticles were prepared using experimental design and equations were
      generated and used to predict relative viscosity, zeta potential and particle
      size under different conditions. This gives us the ability to design tuneable CS
      TPP microparticles with desired size for specific pharmaceutical or forensic
      applications e.g. latent fingerprint visualisation.

PMID- 27894822
TI  - A parallel group randomised open blinded evaluation of Acceptance and Commitment
      Therapy for depression after psychosis: Pilot trial outcomes (ADAPT).
AB  - BACKGROUND: Depression is one of the major contributors to poorer quality of life
      amongst individuals with psychosis and schizophrenia. The study was designed as a
      Pilot Trial to determine the parameters of a larger, definitive pragmatic multi
      centre randomised controlled trial of Acceptance and Commitment Therapy for
      depression after psychosis (ACTdp) for individuals with a diagnosis of
      schizophrenia who also meet diagnostic criteria for major depression. METHODS:
      Participants were required to meet criteria for schizophrenia and major
      depression. Blinded follow-ups were undertaken at 5-months (end of treatment) and
      at 10-months (5-months posttreatment). Primary outcomes were depression as
      measured by the Calgary Depression Scale for Schizophrenia (CDSS) and the Beck
      Depression Inventory (BDI). RESULTS: A total of 29 participants were randomised
      to ACTdp + Standard Care (SC) (n=15) or SC alone (n=14). We did not observe
      significant differences between groups on the CDSS total score at 5-months
      (Coeff=-1.43, 95%CI -5.17, 2.32, p=0.45) or at 10-months (Coeff=1.8, 95%CI -2.10,
      5.69, p=0.36). In terms of BDI, we noted a statistically significant effect in
      favour of ACTdp+SC at 5-months (Coeff=-8.38, 95%CI -15.49, -1.27, p=0.02) but not
      at 10-months (Coeff=-4.85, 95%CI -12.10, 2.39, p=0.18). We also observed
      significant effects on psychological flexibility at 5-months (Coeff=-8.83, 95%CI 
      14.94, -2.71, p<0.01) but not 10-months (Coeff=-4.92, 95%CI -11.09, 1.25,
      p=0.11). IMPLICATIONS: In this first RCT of a psychological therapy with
      depression as the primary outcome, ACT is a promising intervention for depression
      in the context of psychosis. A further large-scale definitive randomised
      controlled trial is required to determine effectiveness. TRIAL REGISTRATION:
      ISRCTN: 33306437.

PMID- 27894826
TI  - Artemin protects cells and proteins against oxidative and salt stress.
AB  - Artemin is an abundant thermostable protein in Artemia encysted embryos under
      environmental stresses. It is confirmed that high regulatory expression of
      artemin is relevant to stress resistance in this crustacean. Here, the protective
      role of artemin from Artemia urmiana has been investigated on survival of
      bacterial cells under salt and oxidative shocks. Also, for continuous monitoring
      of the effect of artemin in prevention of proteins aggregation/inactivation, co
      expression of artemin and luciferase (as an intracellular reporter) in bacterial
      cells was performed. According to the results, residual activity of luciferase in
      artemin expressing E. coli cells exposing to different concentrations of H2O2 and
      NaCl was significantly higher than non-expressing cells. The luciferase activity
      was rapidly lost in control cells under salt treatments while in co-transformed
      cells, the activity was considerably retained at higher salt concentrations.
      Also, analysis from cell viability assays showed that artemin-expressing cells
      exhibited more resistance to both stress conditions. In the present study, we
      document for the first time that artemin can protect proteins and bacterial cells
      against oxidative and salt stress conditions. These results can declare the
      resistance property of this crustacean against harsh environmental conditions.

PMID- 27894827
TI  - Prehensile and non-prehensile tails among syngnathid fishes: what's the
      difference?
AB  - All syngnathid fishes are characterized by a tail with a vertebral column that is
      surrounded by dermal Plates - four per vertebra. Seahorses and pipehorses have
      prehensile tails, a unique characteristic among teleosts that allows them to
      grasp and hold onto substrates. Pipefishes, in contrast, possess a more rigid
      tail. Previous research (Neutens et al., 2014) showed a wide range of variation
      within the skeletal morphology of different members in the syngnathid family. The
      goal of this study is to explore whether the diversity in the three-dimensional
      (3D) shape of different tail types reflects grasping performance, and to what
      degree grasping tails occupy a different and more constrained diversity. For
      this, a 3D morphometrical analysis based on surfaces was performed. Four
      different analyses were performed on the tail skeleton of nine species exhibiting
      different levels of tail grasping capacities (four pipehorse, three seahorse, one
      pipefish and one seadragon species) to examine the intra-individual variation
      across the anteroposterior and dorso-ventral axis. In the two interspecific
      analyses, all vertebrae and all dermal plates were mutually compared. Overall,
      intra-individual variation was larger in species with a prehensile tail. The
      analysis on the vertebrae showed differences in the length and orientation of the
      hemal spine as well as the inclination angle between the anterior and posterior
      surface of the vertebral body. This was observed at an intra-individual level
      across the anteroposterior axis in prehensile species and at an inter-individual
      level between prehensile and non-prehensile species. Across the anteroposterior
      axis in prehensile tails, the overall shape of the plates changes from
      rectangular at the anterior end to square at the posterior end. Across the dorso
      ventral axis, the ventral dermal plates carry a significantly longer caudal spine
      than the dorsal ones in all prehensile-tailed species. It can therefore be
      concluded that prehensile tails exhibit a larger anteroposterior and dorso
      ventral shape variation than non-prehensile ones. However, the hypothesis that
      there is a more constrained shape variation among prehensile species compared to
      non-prehensile ones had to be rejected.

PMID- 27894828
TI  - The effect of strategies, goals and stimulus material on the neural mechanisms of
      emotion regulation: A meta-analysis of fMRI studies.
AB  - Emotion regulation comprises all extrinsic and intrinsic control processes
      whereby people monitor, evaluate and modify the occurrence, intensity and
      duration of emotional reactions. Here we sought to quantitatively summarize the
      existing neuroimaging literature to investigate a) whether different emotion
      regulation strategies are based on different or the same neural networks; b)
      which brain regions in particular support the up- and down-regulation of
      emotions, respectively; and c) to which degree the neural networks realising
      emotion regulation depend on the stimulus material used to elicit emotions. The
      left ventrolateral prefrontal cortex (VLPFC), the anterior insula and the
      supplementary motor area were consistently activated independent of the
      regulation strategy. VLPFC and posterior cingulate cortex were the main regions
      consistently found to be recruited during the up-regulation as well as the down
      regulation of emotion. The down-regulation compared to the up-regulation of
      emotions was associated with more right-lateralized activity while up-regulating
      emotions more strongly modulated activity in the ventral striatum. Finally, the
      process of emotion regulation appeared to be unaffected by stimulus material.

PMID- 27894829
TI  - Plasticity of the postural function to sport and/or motor experience.
AB  - This review addresses the possible structural and functional adaptations of the
      postural function to motor experience. Evidence suggests that postural
      performance and strategy evolve after training in inactive subjects. In trained
      subjects, postural adaptations could also occur, since elite athletes exhibit
      better postural performance than, and different postural strategy to sub-elite
      athletes. The postural adaptations induced are specific to the context in which
      the physical activity is practiced. They appear to be so specific that there
      would be no or only a very slight effect of transfer to non-experienced motor
      tasks (apart from in subjects presenting low initial levels of postural
      performance, such as aged subjects). Yet adaptations could occur as part of the
      interlimb relationship, particularly when the two legs do not display the same
      motor experience. Mechanistic explanations as well as conceptual models are
      proposed to explain how postural adaptations operate according to the nature of
      physical activities and the context in which they are practiced as well as the
      level of motor expertise of individuals.

PMID- 27894830
TI  - The multiple process model of goal-directed reaching revisited.
AB  - Recently our group forwarded a model of speed-accuracy relations in goal-directed
      reaching. A fundamental feature of our multiple process model was the distinction
      between two types of online regulation: impulse control and limb-target control.
      Impulse control begins during the initial stages of the movement trajectory and
      involves a comparison of actual limb velocity and direction to an internal
      representation of expectations about the limb trajectory. Limb-target control
      involves discrete error-reduction based on the relative positions of the limb and
      the target late in the movement. Our model also considers the role of eye
      movements, practice, energy optimization and strategic behavior in limb control.
      Here, we review recent work conducted to test specific aspects of our model. As
      well, we consider research not fully incorporated into our earlier contribution.
      We conclude that a slightly modified and expanded version of our model, that
      includes crosstalk between the two forms of online regulation, does an excellent
      job of explaining speed, accuracy, and energy optimization in goal-directed
      reaching.

PMID- 27894831
TI  - Improvement in routine detection of colistin resistance in E. coli isolated in
      veterinary diagnostic laboratories.
AB  - We have developed a phenotypic method suited to the systematic screening of
      resistance to colistin in E. coli, including those with the mcr-1 gene, by the
      absence of an inhibition zone after an application of a single drop of 8mg/L
      colistin solution on a previously inoculated Mueller-Hinton agar.

PMID- 27894832
TI  - Development of a rapid, one-step screening method for the isolation of
      presumptive proteolytic enterococci.
AB  - Enterococci show higher proteolytic activities than other lactic acid bacteria
      and thus have received considerable attention in scientific literature in recent
      years. Proteolytic enzymes of enterococci have warranted the use of some species
      as starter, adjuncts or protective cultures and as probiotics, while in some
      strains they have also been linked with virulence. Consequently, the isolation
      and identification of proteolytic enterococci is becoming of increasing interest
      and importance. However, current screening methods for proteolytic enterococci
      can be time consuming, requiring a two-step procedure which may take up to 96h.
      This study describes a method, utilising Kanamycin Skim Milk Aesculin Azide
      (KSMEA) agar, for the isolation of proteolytic enterococci in one-step, thereby
      significantly reducing screening time. KSMEA combines the selective properties of
      Kanamycin Aesculin Azide Agar (KAA) with skim milk powder for the detection of
      proteolytic enterococci. Enterococci produced colonies with a black halo on KSMEA
      which were accompanied by a zone of clearing in the media when enterococci were
      proteolytic. KSMEA medium retained the selectivity of KAA, while proteolytic
      enterococci were easily distinguished from non-proteolytic enterococci when two
      known strains were propagated on KSMEA. KSMEA also proved effective at isolating
      and detecting enterococci in raw milk, faeces and soil. Isolates recovered from
      the screen were confirmed as enterococci using genus-specific primers.
      Proteolytic enterococci were present in the raw milk sample only and were easily
      distinguishable from non-proteolytic enterococci and other microorganisms.
      Therefore, KSMEA provides a rapid, one-step screening method for the isolation of
      presumptive proteolytic enterococci.

PMID- 27894833
TI  - Feasibility of Using Ultrasonic Nakagami Imaging for Monitoring Microwave-Induced
      Thermal Lesion in Ex Vivo Porcine Liver.
AB  - The feasibility of using ultrasonic Nakagami imaging to evaluate thermal lesions
      induced by microwave ablation (MWA) in ex vivo porcine liver was explored.
      Dynamic changes in echo amplitudes and Nakagami parameters in the region of the
      MWA-induced thermal lesion, as well as the contrast-to-noise ratio (CNR) between
      the MWA-induced thermal lesion and the surrounding normal tissue, were calculated
      simultaneously during the MWA procedure. After MWA exposure, a bright hyper
      echoic region appeared in ultrasonic B-mode and Nakagami parameter images as an
      indicator of the thermal lesion. Mean values of the Nakagami parameter in the
      thermal lesion region increased to 0.58, 0.71 and 0.91 after 1, 3 and 5 min of
      MVA. There were no significant differences in envelope amplitudes in the thermal
      lesion region among ultrasonic B-mode images obtained after different durations
      of MWA. Unlike ultrasonic B-mode images, Nakagami images were less affected by
      the shadow effect in monitoring of MWA exposure, and a fairly complete hyper
      echoic region was observed in the Nakagami image. The mean value of the Nakagami
      parameter increased from approximately 0.47 to 0.82 during MWA exposure. At the
      end of the postablation stage, the mean value of the Nakagami parameter decreased
      to 0.55 and was higher than that before MWA exposure. CNR values calculated for
      Nakagami parameter images increased from 0.13 to approximately 0.61 during MWA
      and then decreased to 0.26 at the end of the post-ablation stage. The
      corresponding CNR values calculated for ultrasonic B-mode images were 0.24, 0.42
      and 0.17. This preliminary study on ex vivo porcine liver suggested that Nakagami
      imaging have potential use in evaluating the formation of MWA-induced thermal
      lesions. Further in vivo studies are needed to evaluate the potential
      application.

PMID- 27894834
TI  - A podoscopic and descriptive study of foot deformities in patients with Down
      syndrome.
AB  - INTRODUCTION: Subjects with Down syndrome (DS) are known to be affected by
      various foot deformities. Despite the fact that some of these deformities have
      been reported in the literature, a more comprehensive description would be of
      benefit. The aim of this study is to investigate the prevalence of known foot
      deformities in patients with DS and of other previously non-described foot
      anomalies in this population. HYPOTHESIS: Subjects with DS have an increased
      prevalence of foot deformities compared to control subjects. METHODS: Fifty-five
      subjects with DS (age: 14.6+/-7.4 years) had undergone podiatric clinical and
      podoscopic examinations to study their main foot deformities and their
      footprints, respectively. The results of these examinations were compared to
      those of an age-matched asymptomatic control group of fifty-three subjects (age:
      13.4+/-11.2 years). RESULTS: Significantly more prevalent foot deformities were
      found in the DS group: hallux valgus (36.4%), syndactyly between the 2nd and 3rd
      toes (9.1%), grade II pes planus (39.1%) and grade III pes planus (30%).
      Moreover, joint laxity (43.6%) was significantly more prevalent in the DS group.
      Furthermore, the presence of an increased space between the 1st and 2nd toes in
      patients with DS and its prevalence (73.6%) were described for the first time. A
      multivariate analysis revealed a significant relationship between the presence of
      joint laxity and flatfoot in only the control but not the DS group. Other foot
      deformities were found to be consistently more frequent in the DS population but
      not significantly higher than the control group. DISCUSSION: Although subjects
      with DS had significantly greater joint laxity and BMI compared to the control
      group, neither of these factors was found to be related to the increased
      prevalence of flatfoot in DS patients. LEVEL OF EVIDENCE: IV-retrospective study.

PMID- 27894835
TI  - Reducing resource utilization during non-operative treatment of pediatric
      proximal humerus fractures.
AB  - INTRODUCTION: The majority of proximal humeral fractures in the skeletally
      immature are treated non-operatively. Operative indications vary but are largely
      based on degree of displacement. Non-union is rare. Non-operatively treated
      fractures are typically monitored radiographically to assess healing. HYPOTHESIS:
      We hypothesize that the decision to treat fractures operatively is made at the
      time of first imaging and that follow-up X-rays do not lead to a change in
      management. MATERIAL AND METHODS: We retrospectively reviewed the records of 239
      patients treated for proximal humerus fractures over a 5-year period. There were
      225 who were treated non-operatively. Records were reviewed for the number of
      clinic visits and radiographs, as well as any change to operative management
      based on follow-up X-rays. RESULTS: The primary outcome of the study was the
      proportion of proximal humerus fractures, initially treated non-operatively, for
      which displacement or angulation on follow-up radiographs led to a change to
      operative treatment. Secondary outcomes were the number of follow-up radiographs
      obtained after the initial diagnosis and initiation of non-operative treatment.
      Of the 225 patients that were initially managed non-operatively, only 1 patient
      required subsequent surgical management. This patient underwent a proximal
      humerus epiphysiodesis 365 days from injury after development of a partial growth
      arrest. The mean number of fracture clinic visits for patients managed non
      operatively was 2.67 (+/-1.24). The mean number of radiology department visits
      and radiographs obtained was 3.57 (+/-1.44) and 8.36 (+/-3.89) respectively. No
      clinical or radiographic non-unions were identified in these patients. No
      patients suffered a refracture during the review period. DISCUSSION: This study
      shows that of the 239 uncomplicated pediatric proximal humerus fractures treated
      at our hospital over a 5-year period, only 1 had a change in treatment plan, from
      non-operative to operative, based on follow-up radiographs. These data suggest
      that non-operative treatment of proximal humerus fractures seldom results in
      displacement that warrants operative intervention. Moreover, they suggest that
      there is little utility to the routine use of postoperative radiographs in follow
      up of these patients. STUDY DESIGN: Retrospective case series. LEVEL OF EVIDENCE:
      IV.

PMID- 27894836
TI  - Use of complement binding assays to assess the efficacy of antibody mediated
      rejection therapy and prediction of graft survival in kidney transplantation.
AB  - BACKGROUND: The Luminex(r) single antigen bead assay (SAB) is the method of
      choice for monitoring the treatment for antibody-mediated rejection (AMR). A ?50%
      reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence
      intensity (MFI) has been associated with improved kidney allograft survival, and
      C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We
      aimed to investigate if C1q-DSA can be used as a reliable predictor of response
      to therapy and allograft survival in patients with biopsy-proven AMR. METHODS: We
      tested pre- and post-treatment sera of 30 kidney transplant patients receiving
      plasmapheresis and low-dose IVIG for biopsy-proven AMR. IgG-DSA and C1q-DSA MFI
      were measured and correlated with graft loss or survival. Patients were
      classified as nonresponders (NR) when treatment resulted in <50% reduction in MFI
      of IgG-DSA and/or C1q-DSA was detectable following therapy. RESULTS: Differences
      in the percentage of patients deemed NR depended upon the end-point criterion
      (73% by reduction in IgG-DSA MFI vs. 50% by persistent C1q-DSA activity). None of
      the seven patients with <50% reduction of IgG-DSA but non-detectable C1q-DSA
      fixing activity after therapy experienced graft loss, suggesting that C1q-DSA
      activity may better correlate with response. Reduction of C1q-DSA activity
      predicted graft survival better than IgG-DSA in the univariate Cox analysis
      (20.1% vs. 5.9% in NR; log-rank P-value=0.0147). CONCLUSIONS: A rapid reduction
      of DSA concentration below the threshold required for complement activation is
      associated with better graft survival, and C1q-DSA is a better predictor of
      outcomes than IgG-DSA MFI reduction.

PMID- 27894838
TI  - Direct and indirect costs for adverse drug events identified in medical records
      across care levels, and their distribution among payers.
AB  - BACKGROUND: Adverse drug events (ADEs) cause considerable costs in hospitals.
      However, little is known about costs caused by ADEs outside hospitals, effects on
      productivity, and how the costs are distributed among payers. OBJECTIVE: To
      describe the direct and indirect costs caused by ADEs, and their distribution
      among payers. Furthermore, to describe the distribution of patient out-of-pocket
      costs and lost productivity caused by ADEs according to socio-economic
      characteristics. METHOD: In a random sample of 5025 adults in a Swedish county,
      prevalence-based costs for ADEs were calculated. Two different methods were used:
      1) based on resource use judged to be caused by ADEs, and 2) as costs
      attributable to ADEs by comparing costs among individuals with ADEs to costs
      among matched controls. Payers of costs caused by ADEs were identified in medical
      records among those with ADEs (n = 596), and costs caused to individual patients
      were described by socio-economic characteristics. RESULTS: Costs for resource use
      caused by ADEs were ?505 per patient with ADEs (95% confidence interval ?345
      665), of which 38% were indirect costs. Compared to matched controls, the costs
      attributable to ADEs were ?1631, of which ?410 were indirect costs. The local
      health authorities paid 58% of the costs caused by ADEs. Women had higher
      productivity loss than men (?426 vs. ?109, p = 0.018). Out-of-pocket costs
      displaced a larger proportion of the disposable income among low-income earners
      than higher income earners (0.7% vs. 0.2%-0.3%). CONCLUSION: We used two methods
      to identify costs for ADEs, both identifying indirect costs as an important
      component of the overall costs for ADEs. Although the largest payers of costs
      caused by ADEs were the local health authorities responsible for direct costs,
      employers and patients costs for lost productivity contributed substantially. Our
      results indicate inequalities in costs caused by ADEs, by sex and income.

PMID- 27894839
TI  - Relationship of P3b single-trial latencies and response times in one, two, and
      three-stimulus oddball tasks.
AB  - The P300 is one of the most widely studied components of the human event-related
      potential. According to a longstanding view, the P300, and particularly its
      posterior subcomponent (i.e., the P3b), is driven by stimulus categorization.
      Whether the P3b relates to tactical processes involved in immediate responding or
      strategic processes that affect future behavior remains controversial, however.
      It is difficult to determine whether variability in P3b latencies relates to
      variability in response times because of limitations in the methods currently
      available to quantify the latency of the P3b during single trials. In this paper,
      we report results from the Psychomotor Vigilance Task (PVT), the Hitchcock Radar
      Task, and a 3-Stimulus Oddball Task. These represent variants of the one-, two-,
      and three-stimulus oddball paradigms commonly used to study the P3b. The PVT
      requires simple detection, whereas the Hitchcock Radar Task and the 3-Stimulus
      Task require detection and categorization. We apply a novel technique that
      combines hidden semi-Markov models and multi-voxel pattern analysis (HSMM-MVPA)
      to data from the three experiments. HSMM-MVPA revealed a processing stage in each
      task corresponding to the P3b. Trial-by-trial variability in the latency of the
      processing stage correlated with response times in the Hitchcock Radar Task and
      the 3-Stimulus Task, but not the PVT. These results indicate that the P3b
      reflects a stimulus categorization process, and that its latency is strongly
      associated with response times when the stimulus must be categorized before
      responding. In addition to those theoretical insights, the ability to detect the
      onset of the P3b and other components on a single-trial basis using HSMM-MVPA
      opens the door for new uses of mental chronometry in cognitive neuroscience.

PMID- 27894840
TI  - Overexpression of MTERF4 promotes the amyloidogenic processing of APP by
      inhibiting ADAM10.
AB  - Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid
      (Abeta) peptide in the brain, which is produced by the proteolysis of beta
      amyloid precursor protein (APP). Recently, the mitochondrial transcription factor
      4 (MTERF4), a member of the MTERF family, was implicated in regulating
      mitochondrial DNA transcription and directly in controlling mitochondrial
      ribosomal translation. The present study identified a novel role for MTERF4 in
      shifting APP processing toward the amyloidogenic pathway. The levels of MTERF4
      protein were significantly increased in the hippocampus of APP/PS1 mice. In
      addition, the overexpression of MTERF4 induced a significant increase in the
      levels of APP protein and secreted Abeta42 in HEK293-APPswe cells compared with
      control cells. Further, MTERF4 overexpression shifted APP processing from alpha
      to beta-cleavage, as indicated by decreased C83 levels and elevated C99 levels.
      Finally, the MTERF4 overexpression suppressed a disintegrin and metalloproteinase
      10 (ADAM10) expression via a transcriptional mechanism. Taken together, these
      results suggest that MTERF4 promotes the amyloidogenic processing of APP by
      inhibiting ADAM10 in HEK293-APPswe cells; therefore, MTERF4 may play an important
      role in the pathogenesis of AD.

PMID- 27894837
TI  - CD4+ virtual memory: Antigen-inexperienced T cells reside in the naive,
      regulatory, and memory T cell compartments at similar frequencies, implications
      for autoimmunity.
AB  - It is widely accepted that central and effector memory CD4+ T cells originate
      from naive T cells after they have encountered their cognate antigen in the
      setting of appropriate co-stimulation. However, if this were true the diversity
      of T cell receptor (TCR) sequences within the naive T cell compartment should be
      far greater than that of the memory T cell compartment, which is not supported by
      TCR sequencing data. Here we demonstrate that aged mice with far fewer naive T
      cells, respond to the model antigen, hen eggwhite lysozyme (HEL), by utilizing
      the same TCR sequence as their younger counterparts. CD4+ T cell repertoire
      analysis of highly purified T cell populations from naive animals revealed that
      the HEL-specific clones displayed effector and central "memory" cell surface
      phenotypes even prior to having encountered their cognate antigen. Furthermore,
      HEL-inexperienced CD4+ T cells were found to reside within the naive, regulatory,
      central memory, and effector memory T cell populations at similar frequencies and
      the majority of the CD4+ T cells within the regulatory and memory populations
      were unexpanded. These findings support a new paradigm for CD4+ T cell maturation
      in which a specific clone can undergo a differentiation process to exhibit a
      "memory" or regulatory phenotype without having undergone a clonal expansion
      event. It also demonstrates that a foreign-specific T cell is just as likely to
      reside within the regulatory T cell compartment as it would the naive
      compartment, arguing against the specificity of the regulatory T cell compartment
      being skewed towards self-reactive T cell clones. Finally, we demonstrate that
      the same set of foreign and autoreactive CD4+ T cell clones are repetitively
      generated throughout adulthood. The latter observation argues against T cell
      depleting strategies or autologous stem cell transplantation as therapies for
      autoimmunity-as the immune system has the ability to regenerate pathogenic
      clones.

PMID- 27894841
TI  - In vitro investigation of ultrasound-induced oxidative stress on human lens
      epithelial cells.
AB  - The effect of ultrasound exposure on human lens epithelial cells (HLE-B3) was
      investigated in vitro, specifically on the generation of oxidative stress upon
      ultrasound application using various clinically-relevant settings. In addition to
      ultrasound-induced heat effects, oxidative stress has been recently proposed as
      one of the main mechanisms for ultrasound-induced effects on human cells. In this
      work, the levels of biocompatibility and generation of oxidative stress by
      exposure of ultrasound to HLE-B3 were evaluated quantitatively and qualitatively
      by the MTT assay, Live/Dead assay, reactive oxygen species (ROS) and
      intracellular calcium level. Oxidative stress induction is traditionally achieved
      through administrations of H2O2 and thus the administration of H2O2 was used as
      the positive control group for comparison herein. Concerning the administrations
      of H2O2 are considered invasive and may potentially have side effects, ultrasound
      as physical stimulation could be a safer and non-invasive method to induce
      similar oxidative stress environments. The effect of ultrasound on cell viability
      and induction of oxidative stress increases with ultrasound intensity. The result
      reveals that the continuous ultrasound has a positive impact on the oxidative
      stress levels but does negatively on the cell viability, as compared to the
      pulsed ultrasound. Furthermore, our work demonstrates that the exposure of 58 kPa
      continuous ultrasound without microbubbles can maintain acceptable cell viability
      and produce oxidative stress effects similar to the traditional administrations
      of H2O2. In summary, exposure of ultrasound can generate oxidative stress
      comparable to traditional administrations of H2O2. The effect of generating
      oxidative stress is adjustable through ultrasound parameters, including the
      pulsed or continuous wave, the intensity of ultrasound and addition of
      microbubbles.

PMID- 27894842
TI  - Energetic basis on interactions between ferredoxin and ferredoxin NADP+ reductase
      at varying physiological conditions.
AB  - In spite of a number of studies to characterize ferredoxin (Fd):ferredoxin NADP+
      reductase (FNR) interactions at limited conditions, detailed energetic
      investigation on how these proteins interact under near physiological conditions
      and its linkage to FNR activity are still lacking. We herein performed systematic
      Fd:FNR binding thermodynamics using isothermal titration calorimetry (ITC) at
      distinct pH (6.0 and 8.0), NaCl concentrations (0-200 mM), and temperatures (19
      28  degrees C) for mimicking physiological conditions in chloroplasts.
      Energetically unfavorable endothermic enthalpy changes were accompanied by Fd:FNR
      complexation at all conditions. This energetic cost was compensated by favorable
      entropy changes, balanced by conformational and hydrational entropy. Increases in
      the NaCl concentration and pH weakened interprotein affinity due to the less
      contribution of favorable entropy change regardless of energetic gains from
      enthalpy changes, suggesting that entropy drove complexation and modulated
      affinity. Effects of temperature on binding thermodynamics were much smaller than
      those of pH and NaCl. NaCl concentration and pH-dependent enthalpy and heat
      capacity changes provided clues for distinct binding modes. Moreover, decreases
      in the enthalpy level in the Hammond's postulate-based energy landscape
      implicated kinetic advantages for FNR activity. All these energetic interplays
      were comprehensively demonstrated by the driving force plot with the enthalpy
      entropy compensation which may serve as an energetic buffer against outer
      stresses. We propose that high affinity at pH 6.0 may be beneficial for
      protection from proteolysis of Fd and FNR in rest states, and moderate affinity
      at pH 8.0 and proper NaCl concentrations with smaller endothermic enthalpy
      changes may contribute to increase FNR activity.

PMID- 27894843
TI  - MiR-509-5p suppresses the proliferation, migration, and invasion of non-small
      cell lung cancer by targeting YWHAG.
AB  - Dysregulation of microRNAs (miRNAs) expression is prevalent in human malignancy
      development and progression. As previously reported, miR-509-5p has been
      identified as a tumor suppressor in various cancers, but its role and functional
      mechanism in non-small lung cancer (NSCLC) remains unknown. In the present study,
      we found that miR-509-5p was significantly downregulated in NSCLC tissues and
      cell lines using Quantitative real-time PCR (qRT-PCR). In addition,
      overexpression of miR-509-5p markedly inhibited the proliferation, migration,
      invasion and phosphorylation of Akt of NSCLC cells. Moreover, we identified
      tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma
      (YWHAG) as a direct target of miR-509-5p. Knockdown of YWHAG mimicked the
      inhibitory effects of miR-509-5p on NSCLC cells for proliferation and motility.
      Finally, the negative correlation between miR-509-5p and YWHAG expression in
      NSCLC specimens was demonstrated. Taken together, our present study revealed the
      tumor suppressive role of miR-509-5p in NSCLC by targeting YWHAG, suggesting that
      miR-509-5p/YWHAG axis might be considered as a novel and potential target for
      clinical diagnosis and therapeutics of NSCLC.

PMID- 27894844
TI  - The tricarboxylic acid cycle activity in cultured primary astrocytes is strongly
      accelerated by the protein tyrosine kinase inhibitor tyrphostin 23.
AB  - Tyrphostin 23 (T23) is a well-known inhibitor of protein tyrosine kinases and has
      been considered as potential anti-cancer drug. T23 was recently reported to
      acutely stimulate the glycolytic flux in primary cultured astrocytes. To
      investigate whether T23 also affects the tricarboxylic acid (TCA) cycle, we
      incubated primary rat astrocyte cultures with [U-13C]glucose in the absence or
      the presence of 100 MUM T23 for 2 h and analyzed the 13C metabolite pattern.
      These incubation conditions did not compromise cell viability and confirmed that
      the presence of T23 doubled glycolytic lactate production. In addition, T23
      treatment strongly increased the molecular carbon labeling of the TCA cycle
      intermediates citrate, succinate, fumarate and malate, and significantly
      increased the incorporation of 13C-labelling into the amino acids glutamate,
      glutamine and aspartate. These results clearly demonstrate that, in addition to
      glycolysis, also the mitochondrial TCA cycle is strongly accelerated after
      exposure of astrocytes to T23, suggesting that a protein tyrosine kinase may be
      involved in the regulation of the TCA cycle in astrocytes.

PMID- 27894845
TI  - Thromboelastography demonstrates perioperative hypercoagulability in hepato
      pancreato-biliary patients and supports routine administration of preoperative
      and early postoperative venous thromboembolism chemoprophylaxis.
AB  - BACKGROUND: We hypothesized hepato-pancreato-biliary (HPB) surgery patients are
      more likely to be hypercoagulable than hypocoagulable, and that bleeding risks
      from VTE chemoprophylaxis are low. This study sought to use thromboelastography
      (TEG) to compare coagulation profiles with bleeding/thrombotic events in HPB
      patients receiving standardized perioperative chemoprophylaxis. METHODS:
      Consecutive patients undergoing HPB resections by three surgeons at one
      institution (January 2014-December 2015) received preoperative and early
      postoperative VTE chemoprophylaxis and were evaluated with TEGs. Coagulation
      profiles were compared to bleeding/thrombotic events. RESULTS: Of 87 total
      patients, 83 (95.4%) received preoperative chemoprophylaxis and 100% received it
      postoperatively. Median estimated blood loss was 190 ml. Only 2 (2.3%) patients
      received intraoperative transfusions. None required transfusions at 72-hours.
      Only 2 were transfused within 30 days. There was 1 (1.1%) 30-day VTE event. Of 83
      preoperative TEGs, 29 (34.9%) were hypercoagulable and only 8 (9.6%) were
      hypocoagulable/fibrinolytic. Of 73 postoperative TEGs, 34 (46.6%) were
      hypercoagulable and just 8 (11.0%) were hypocoagulable/fibrinolytic. .
      CONCLUSION: With routine perioperative chemoprophylaxis, both VTE and bleeding
      events were negligible. Perioperative TEG revealed a considerable proportion
      (46.6%) of HPB patients were hypercoagulable. HPB patients can receive
      standardized preoperative/early postoperative VTE chemoprophylaxis with effective
      results and minimal concern for perioperative hemorrhage.

PMID- 27894846
TI  - Maintaining physical exercise as a matter of synchronising practices: Experiences
      and observations from training in Mixed Martial Arts.
AB  - This paper is concerned with the establishment, maintenance, and decline of
      physical exercise practices. Drawing on experiences and observations taken from a
      carnal ethnography and rhythmanalysis of the practices involved in training in
      Mixed Martial Arts (MMA), I argue that maintaining this physical exercise
      practice is not straightforwardly an outcome of individual commitment, access to
      facilities, or the availability of free time. It rather depends on the
      synchronisation of practices: those of MMA, those that support MMA, and those
      that more broadly make up everyday life. This research suggests that increasing
      rates of physical activity might be better fostered through facilitating the
      integration of combinations of healthy activities into everyday life.

PMID- 27894847
TI  - PCR screening of tick-borne agents in sensitive conservation areas, Southeast
      Portugal.
AB  - The Southeast region of Portugal, particularly the Guadiana valley, is currently
      the reintroduction territory of Lynx pardinus (Iberian lynx), one of the most
      endangered felids in the world that is only found in the Iberian Peninsula. Over
      the last century, populations have declined, placing L. pardinus at extremely
      high risk of extinction in the wild and relying on reintroduction projects. Among
      the aspects taken into account in the establishment of new populations is the
      sanitary status of the selected habitats, especially concerning infectious
      diseases, including tick-borne pathogens (TBPs). This study presents the results
      of TBPs survey on ticks collected at sensitive conservation areas of Southeast
      Portugal. From 2012 to 2014, 231 ticks obtained from vegetation, sympatric
      domestic and wild animals were submitted for analysis. The presence of Babesia
      spp., Cytauxzoon spp., Theileria spp., Hepatozoon spp., Anaplasma spp., Ehrlichia
      spp., Candidatus Neoehrlichia mikurensis, among other Anaplasmataceae, and
      Coxiella burnetii were investigated by PCR. Six tick species were recorded,
      Dermacentor marginatus (n = 13/5.6%), Hyalomma lusitanicum (n = 175/75.8%),
      Ixodes ricinus (n = 4/1.7%), Rhipicephalus bursa (n = 7/3.0%), R. pusillus (n =
      21/9.1%) and R. sanguineus sensu lato (n = 11/4.8%). The molecular screening
      confirmed the presence of two tick-borne pathogens, C. burnetii (N = 34) and
      Anaplasma platys (N = 1), and one tick-endosymbiont, Candidatus Midichloria
      mitochondrii (N = 45). The results obtained provide new information on the
      circulation of ticks and TBPs with potential veterinary importance in Iberian
      lynx habitat.

PMID- 27894848
TI  - Oral extramedullary plasmacytoma in a HIV positive patient.

PMID- 27894849
TI  - A global view of regulatory networks in lung cancer: An approach to understand
      homogeneity and heterogeneity.
AB  - A number of new biotechnologies are used to identify potential biomarkers for the
      early detection of lung cancer, enabling a personalized therapy to be developed
      in response. The combinatorial cross-regulation of hundreds of biological
      function-specific transcription factors (TFs) is defined as the understanding of
      regulatory networks of molecules within the cell. Here we integrated global
      databases with 537 patients with lung adenocarcinoma (ADC), 140 with lung
      squamous carcinoma (SCC), 9 with lung large-cell carcinoma (LCC), 56 with small
      cell lung cancer (SCLC), and 590 without cancer with the understanding of TF
      functions. The present review aims at the homogeneity or heterogeneity of gene
      expression profiles among subtypes of lung cancer. About 5, 136, 52, or 16 up
      regulated or 19, 24, 122, or 97down-regulated type-special TF genes were
      identified in ADC, SCC, LCC or SCLC, respectively. DNA-binding and transcription
      regulator activity associated genes play a dominant role in the differentiation
      of subtypes in lung cancer. Subtype-specific TF gene regulatory networks with
      elements should be an alternative for diagnostic and therapeutic targets for
      early identification of lung cancer and can provide insightful clues to etiology
      and pathogenesis.

PMID- 27894850
TI  - Generating the evidence base for malaria elimination: the situation in Haiti.

PMID- 27894852
TI  - Effect of warming bupivacaine 0.5% on ultrasound-guided axillary plexus block.
      Randomized prospective double-blind study.
AB  - OBJECTIVE: To evaluate the effect of warming bupivacaine 0.5% on ultrasound
      guided axillary brachial plexus block. STUDY DESIGN: Prospective, randomized,
      double-blind. PATIENTS AND METHODS: Eighty patients undergoing elective or
      emergency surgery beyond the distal third of the upper limb were divided into two
      groups of 40 patients: the warm group received 15mL bupivacaine 0.5% heated to 37
      degrees C; the cold group received 15mL 0.5% bupivacaine stored for at least
      24hours in the lower compartment of a refrigerator at 13-15 degrees C. Onset and
      duration of sensory and motor blocks were evaluated every 5minutes for 40minutes.
      Postoperative pain was evaluated at 1, 3, 6, 12 and 24hours. Effective analgesia
      time was recorded as the interval between anesthetic injection and the first
      analgesia requirement (VAS>30mm). RESULTS: Time to onset of sensory and motor
      block was significantly shorter in the warm group, and mean duration of sensory
      and motor block and of postoperative analgesia significantly longer. CONCLUSION:
      Warming bupivacaine 0.5% to 37 degrees C accelerated onset of sensory and motor
      block and extended action duration.

PMID- 27894853
TI  - Concurrent carpal tunnel syndrome and pronator syndrome: A retrospective study of
      21 cases.
AB  - PURPOSE: Concurrent carpal tunnel syndrome and pronator syndrome are rarely
      considered and the proximal compression sites are easily overlooked. We
      retrospectively studied 21 concurrent cases in our series from 2009 to 2015 and
      report the results. PATIENTS AND METHODS: The typical symptoms were pain,
      tingling, and numbness of the radial 31/2 digits. If paresthesia involved the
      thenar eminence and proximal forearm pain was noted in cases of carpal tunnel
      syndrome, carpal tunnel syndrome combined with pronator syndrome was considered.
      Additionally, nocturnal paresthesia symptoms are absent in pronator syndrome.
      Therefore, if nocturnal symptoms occurred in pronator syndrome, carpal tunnel
      syndrome was considered. We included concurrent carpal tunnel syndrome and
      pronator syndrome. We used arthroscopic release of the transverse carpal ligament
      and open decompression for the pronator teres in cases that underwent surgery for
      the first time. However, recurrent carpal tunnel cases were treated with the open
      carpal tunnel release and open pronator decompression procedure in our hospital.
      The two-point discrimination was used for evaluation of sensory deficit. The grip
      and pinch (thumb tip to index) strength were measured by dynamometry and pinch
      gauge respectively. RESULTS: We retrospectively reviewed 344 cases of sustained
      carpal tunnel syndrome or pronator syndrome from the medical records of our
      institution. Of the 344 cases, 322 involved carpal tunnel syndrome alone, 1
      involved pronator syndrome alone, and 21 involved carpal tunnel syndrome combined
      with pronator syndrome. The 21 cases of carpal tunnel syndrome combined with
      pronator syndrome were included in our study. Among the total cases of carpal
      tunnel syndrome, 6% (21/343) had pronator syndrome. The patients included 3 men
      and 18 women with a mean age of 52 years (range: 42-69 years). Electromyography
      (EMG) and nerve conduction studies were routinely performed. Postoperative
      evaluation showed that 15 out of 21 patients (71%) were completely relieved of
      pain and paresthesia and had no sensory deficit, satisfied strength improved
      (>85% of the opposite hand). Six patients (29%) had occasional paresthesia and
      pain, but no sensory deficit; grip and pinch strength deficit were recorded (<50%
      of the opposite hand). Six cases of these partially relieved patients had
      recurrent carpal tunnel syndrome but no one needed to perform tendon transfer for
      thenar muscle atrophy. CONCLUSION: It is important to consider the diagnosis of
      double crush syndrome of the median nerve, as carpal tunnel syndrome combined
      with pronator syndrome may impede treatment of the carpal tunnel syndrome.

PMID- 27894851
TI  - Effectiveness of insecticide-treated bednets in malaria prevention in Haiti: a
      case-control study.
AB  - BACKGROUND: Insecticide-treated bednets (ITNs) are effective in preventing
      malaria where vectors primarily bite indoors and late at night, but their
      effectiveness is uncertain where vectors bite outdoors and earlier in the
      evening. We studied the effectiveness of ITNs following a mass distribution in
      Haiti from May to September, 2012, where the Anopheles albimanus vector bites
      primarily outdoors and often when people are awake. METHODS: In this case-control
      study, we enrolled febrile patients presenting to outpatient departments at 17
      health facilities throughout Haiti from Sept 4, 2012, to Feb 27, 2014, who were
      tested with malaria rapid diagnostic tests (RDTs), and administered
      questionnaires on ITN use and other risk factors. Cases were defined by positive
      RDT and controls were febrile patients from the same clinic with a negative RDT.
      Our primary analysis retrospectively matched cases and controls by age, sex,
      location, and date, and used conditional logistic regression on the matched
      sample. A sensitivity analysis used propensity scores to match patients on ITN
      use propensity and analyse malaria among ITN users and non-users. Additional ITN
      bioefficacy and entomological data were collected. FINDINGS: We enrolled 9317
      patients, including 378 (4%) RDT-positive cases. 1202 (13%) patients reported ITN
      use. Post-hoc matching of cases and controls yielded 362 cases and 1201 matched
      controls, 19% (333) of whom reported consistent campaign net use. After using
      propensity scores to match on consistent campaign ITN use, 2298 patients,
      including 138 (7%) RDT-positive cases, were included: 1149 consistent campaign
      ITN users and 1149 non-consistent campaign ITN users. Both analyses revealed that
      ITNs did not significantly protect against clinical malaria (odds ratio
      [OR]=0.95, 95% CI 0.68-1.32, p=0.745 for case-control analysis; OR=0.95, 95% CI
      0.45-1.97, p=0.884 for propensity score analysis). ITN and entomological data
      indicated good ITN physical integrity and bioefficacy, and no permethrin
      resistance among local mosquitoes. INTERPRETATION: We found no evidence that mass
      ITN campaigns reduce clinical malaria in this observational study in Haiti;
      alternative malaria control strategies should be prioritised. FUNDING: The Global
      Fund to Fight AIDS, Tuberculosis, and Malaria, and the US-based Centers for
      Disease Control and Prevention (CDC).

PMID- 27894854
TI  - WITHDRAWN: Decreased level of endogenous ghrelin is involved in the progression
      of lung injury induced by oleic acid.
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- 27894855
TI  - Galloylquinic acid derivatives from Copaifera langsdorffii leaves display
      gastroprotective activity.
AB  - Nine new methylated galloylquinic acids were isolated from an aqueous fraction of
      Copaifera langsdorffii (Fabaceae-Caesalpinioideae) leaf hydroalcoholic extract (3
      8, 11, 12, and 14), along with three known methylated galloylquinic acids (1, 2,
      and 15) and four galloylquinic acids (9, 10, 13, and 16). These compounds were
      characterized by nuclear magnetic resonance spectroscopy and mass spectrometry.
      They were further tested in a gastroprotection assay (Ethanol-HCl induced ulcer
      model in mice), in which all of them significantly reduced the total lesion area,
      and increased the cure ratio in comparison with pantoprazole. Also, the tested
      compounds displayed cytotoxicity against gastric adenocarcinoma cells.

PMID- 27894856
TI  - Glycopeptide resistance: Links with inorganic phosphate metabolism and cell
      envelope stress.
AB  - Antimicrobial resistance is a critical health issue today. Many pathogens have
      become resistant to many or all available antibiotics and limited new antibiotics
      are in the pipeline. Glycopeptides are used as a 'last resort' antibiotic
      treatment for many bacterial infections, but worryingly, glycopeptide resistance
      has spread to very important pathogens such as Enterococcus faecium and
      Staphylococcus aureus. Bacteria confront multiple stresses in their natural
      environments, including nutritional starvation and the action of cell-wall
      stressing agents. These stresses impact bacterial susceptibility to different
      antimicrobials. This article aims to review the links between glycopeptide
      resistance and different stresses, especially those related with cell-wall
      biosynthesis and inorganic phosphate metabolism, and to discuss promising
      alternatives to classical antibiotics to avoid the problem of antimicrobial
      resistance.

PMID- 27894857
TI  - Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer
      Cell Antileukemia and FcgammaRIIIa-Triggered Responses.
AB  - Cytokine-induced memory-like natural killer (NK) cells differentiate after short
      term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector
      function in response to cytokines or tumor targets for weeks after the initial
      preactivation. Conventional NK cell function depends on a licensing signal,
      classically delivered by an inhibitory receptor engaging its cognate MHC class I
      ligand. How licensing status integrates with cytokine-induced memory-like NK cell
      responses is unknown. We investigated this interaction using killer cell
      immunoglobulin-like receptor- and HLA-genotyped primary human NK cells. Memory
      like differentiation resulted in enhanced IFN-gamma production triggered by
      leukemia targets or FcgammaRIIIa ligation within licensed NK cells, which
      exhibited the highest functionality of the NK cell subsets interrogated. IFN
      gamma production by unlicensed memory-like NK cells was also enhanced to a level
      comparable with that of licensed control NK cells. Mechanistically, differences
      in responses to FcgammaRIIIa-based triggering were not explained by alterations
      in key signaling intermediates, indicating that the underlying biology of memory
      like NK cells is distinct from that of adaptive NK cells in human cytomegalovirus
      positive individuals. Additionally, memory-like NK cells responded robustly to
      cytokine receptor restimulation with no impact of licensing status. These results
      demonstrate that both licensed and unlicensed memory-like NK cell populations
      have enhanced functionality, which may be translated to improve leukemia
      immunotherapy.

PMID- 27894858
TI  - Elbow dislocation with ipsilateral fracture of the distal radius associated with
      a brachial artery injury: A new pathological condition of traumatic origin.
AB  - Elbow dislocation associated with ipsilateral fracture of the distal radius and a
      brachial artery injury is an uncommon traumatic entity. The two references of
      this injury combination appeared in 2015, although both authors did not realise
      that they were the first two cases published in the medical literature. Although
      mentioned in the text of the articles, no mention was made of the fracture of the
      distal radius in the titles. The purpose of this paper is to present three cases
      with this new traumatic pathological entity, explaining its pathogenetic
      mechanism, the treatment used, and the results obtained.

PMID- 27894859
TI  - Brown tumour in phalanx of the ring finger due to chronic kidney failure. A case
      report.
AB  - Brown tumours are highly vascular lytic bone lesions found in primary and
      secondary hyperparathyroidism. The brown term is given due to the red-brown
      colour of the tissue, which is due to the accumulation of hemosiderin. The case
      is presented of a 29 year-old male with chronic renal failure, who had a mass in
      the tip of the ring finger after a trauma of 4 months onset, which had increased
      progressively in size and pain. He was treated surgically, by amputation, with no
      recurrence 10 months after the surgery.

PMID- 27894861
TI  - Development of a competitive double antibody lateral flow assay for the detection
      of antibodies specific to glycoprotein B of Aujeszky's disease virus in swine
      sera.
AB  - Three lateral flow assays (LFAs) for the detection of antibodies against
      glycoprotein B (gB) of Aujeszky's disease virus (ADV) in swine sera: a
      competitive double antibody sandwich LFA without a preincubation step (CDAS-gB
      LFA), a CDAS-gB-LFA with a preincubation step (pCDAS-gB-LFA), and a competitive
      direct gB-LFA have been developed and were compared with each other and with a gB
      ELISA. The assays are based on monoclonal antibodies to immunodominant epitopes
      of ADV gB. The pCDAS-gB-LFA proved to be the most specific and sensitive assay to
      detect antibodies directed to ADV gB. The specificity and sensitivity of the
      pCDAS-gB-LFA with the use of an LFA reader for test line intensity measurements
      were 97.6 and 94.9%, respectively. The lower diagnostic sensitivity of the pCDAS
      gB-LFA compared to a gB-ELISA reflects its reduced analytical sensitivity, which
      was shown in titration experiments with positive sera. The pCDAS-gB-LFA, using
      the reader-based and visual detection modes, showed good agreement in respect to
      specificity; however, the LFA reader detection provided a higher diagnostic and
      analytical sensitivity compared to visual detection. The developed pCDAS-gB-LFA
      is a rapid, sensitive, and specific method for the detection of antibodies to ADV
      gB and can be used for screening ADV-infected swine in unvaccinated herds.

PMID- 27894860
TI  - Pediatric Ovarian Torsion and its Recurrence: A Multicenter Study.
AB  - STUDY OBJECTIVE: To report results of a retrospective multicentric Italian survey
      concerning the management of pediatric ovarian torsion (OT) and its recurrence.
      DESIGN: Multicenter retrospective cohort study. SETTING: Italian Units of
      Pediatric Surgery. PARTICIPANTS: Participants were female aged 1-14 years of age
      with surgically diagnosed OT between 2004 and 2014. INTERVENTIONS: Adnexal
      detorsion, adnexectomy, mass excision using laparoscopy or laparotomy. Different
      kinds of oophoropexy (OPY) for OT or recurrence, respectively. MAIN OUTCOME
      MEASURES: A total of 124 questionnaires were returned and analyzed to understand
      the current management of pediatric OT and its recurrence. The questionnaires
      concerned patient age, presence of menarche, OT site, presence and type of mass,
      performed procedure, OPY technique adopted, intra- and postoperative
      complications, recurrence and site, procedure performed for recurrence, OPY
      technique for recurrence, and 1 year follow-up of detorsed ovaries. RESULTS: Mean
      age at surgery was 9.79 +/- 3.54 years. Performed procedures were open
      adnexectomy (52 of 125; 41.6%), laparoscopic adnexectomy (25 of 125; 20%), open
      detorsion (10 of 125; 8%), and laparoscopic detorsion (38 of 125; 30.4%).
      Recurrence occurred in 15 of 125 cases (12%) and resulted as significant (P =
      .012) if associated with a normal ovary at the first episode of torsion.
      Recurrence occurred only in 1 of 19 cases after OPY (5.2%). Ultrasonographic
      results of detorsed ovaries were not significant whether an OPY was performed or
      not (P = 1.00). CONCLUSION: Unfortunately, oophorectomy and open technique are
      still widely adopted even if not advised. Recurrence is not rare and the risk is
      greater in patients without ovarian masses. OPY does not adversely affect
      ultrasonographic results at 1 year. When possible OPY should be performed at the
      first episode of OT.

PMID- 27894862
TI  - HIV drug resistance testing among patients failing second line antiretroviral
      therapy. Comparison of in-house and commercial sequencing.
AB  - INTRODUCTION: HIV genotyping is often unavailable in low and middle-income
      countries due to infrastructure requirements and cost. We compared genotype
      resistance testing in patients with virologic failure, by amplification of HIV
      pol gene, followed by "in-house" sequencing and commercial sequencing. METHODS:
      Remnant plasma samples from adults and children failing second-line ART were
      amplified and sequenced using in-house and commercial di-deoxysequencing, and
      analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug
      resistance mutations were determined using the Stanford HIV drug resistance
      database. RESULTS: Twenty-six of 28 samples were amplified and 25 were
      successfully genotyped. Comparison of average percent nucleotide and amino acid
      identities between 23 pairs sequenced in both laboratories were 99.51 (+/-0.56)
      and 99.11 (+/-0.95), respectively. All pairs clustered together in phylogenetic
      analysis. Sequencing analysis identified 6/23 pairs with mutation discordances
      resulting in differences in phenotype, but these did not impact future regimens.
      CONCLUSIONS: The results demonstrate our ability to produce good quality drug
      resistance data in-house. Despite discordant mutations in some sequence pairs,
      the phenotypic predictions were not clinically significant.

PMID- 27894863
TI  - Molecular evidence for Toxoplasma gondii in feeding and questing Ixodes ricinus
      ticks.
AB  - The aim of the present study was to detect Toxoplasma gondii in ticks collected
      from ponies and field vegetation and to determine the role of Shetland ponies as
      a potential reservoir host for T. gondii. A total of 1737 feeding Ixodes ricinus
      collected from 49 horses and 371 questing ticks were tested by PCR and sequencing
      for the presence and genotyping of T. gondii. All ticks were examined in a
      previous study to detect and identify pathogenic bacterial species. The aim of
      this study was also to detect co-infection of ticks with these bacteria and T.
      gondii. Genotyping of the sequenced B1 gene revealed that detected T. gondii
      strains represented genotype I, which is pathogenic for humans. T. gondii
      genotype I was detected in 4.5% of all I. ricinus, including in 2.99% of feeding
      ticks and in 10.24% of questing ticks; this difference was statistically
      significant. Thus, the above results indicate that ponies probably are not an
      essential host for the detected sporozoan. Infections with more than one
      pathogenic species were rare and involved mostly T. gondii and Borrelia
      burgdorferi sensu lato. Our results confirmed the presence of T. gondii in I.
      ricinus and showed a new geographical habitat of T. gondii occurring in I.
      ricinus ticks in Poland.

PMID- 27894864
TI  - Integrative approaches for prediction of cardiotoxic drug effects and mitigation
      strategies.

PMID- 27894865
TI  - The genetic component of bicuspid aortic valve and aortic dilation. An exome-wide
      association study.
AB  - BACKGROUND: Bicuspid aortic valve is the most common cardiovascular congenital
      malformation affecting 2% of the general population. The incidence of life
      threatening complications, the high heritability, and familial clustering rates
      support the interest in identifying risk or protective genetic factors. The main
      objective of the present study was to identify population-based genetic variation
      associated with bicuspid aortic valve and concomitant ascending aortic dilation.
      MATERIALS AND METHODS: A cross-sectional exome-wide association study was
      conducted in 565 Spanish cases and 484 controls. Single-marker and gene-based
      association analyses enriched for low frequency and rare genetic variants were
      performed on this discovery stage cohort and for the subsets of cases with and
      without ascending aortic dilation. Discovery-stage association signals and
      additional markers indirectly associated with bicuspid aortic valve, were
      genotyped in a replication cohort that comprised 895 Caucasian cases and 1483
      controls. RESULTS: Although none of the association signals were consistent
      across series, the involvement of HMCN2 in calcium metabolism and valve
      degeneration caused by calcium deposit, and a nominal but not genome-wide
      significant association, supported it as an interesting gene for follow-up
      studies on the genetic susceptibility to bicuspid aortic valve. CONCLUSIONS: The
      absence of a genome-wide significant association signal shows this valvular
      malformation may be more genetically complex than previously believed. Exhaustive
      phenotypic characterization, even larger datasets, and collaborative efforts are
      needed to detect the combination of rare variants conferring risk which, along
      with specific environmental factors, could be causing the development of this
      disease.

PMID- 27894866
TI  - Transcriptional regulation of the sodium channel gene (SCN5A) by GATA4 in human
      heart.
AB  - Aberrant expression of the sodium channel gene (SCN5A) has been proposed to
      disrupt cardiac action potential and cause human cardiac arrhythmias, but the
      mechanisms of SCN5A gene regulation and dysregulation still remain largely
      unexplored. To gain insight into the transcriptional regulatory networks of
      SCN5A, we surveyed the promoter and first intronic regions of the SCN5A gene,
      predicting the presence of several binding sites for GATA transcription factors
      (TFs). Consistent with this prediction, chromatin immunoprecipitation (ChIP) and
      sequential ChIP (Re-ChIP) assays show co-occupancy of cardiac GATA TFs GATA4 and
      GATA5 on promoter and intron 1 SCN5A regions in fresh-frozen human left ventricle
      samples. Gene reporter experiments show GATA4 and GATA5 synergism in the
      activation of the SCN5A promoter, and its dependence on predicted GATA binding
      sites. GATA4 and GATA6 mRNAs are robustly expressed in fresh-frozen human left
      ventricle samples as measured by highly sensitive droplet digital PCR (ddPCR).
      GATA5 mRNA is marginally but still clearly detected in the same samples.
      Importantly, GATA4 mRNA levels are strongly and positively correlated with SCN5A
      transcript levels in the human heart. Together, our findings uncover a novel
      mechanism of GATA TFs in the regulation of the SCN5A gene in human heart tissue.
      Our studies suggest that GATA5 but especially GATA4 are main contributors to
      SCN5A gene expression, thus providing a new paradigm of SCN5A expression
      regulation that may shed new light into the understanding of cardiac disease.

PMID- 27894868
TI  - The 91-205 amino acid region of AcMNPV ORF34 (Ac34), which comprises a potential
      C3H zinc finger, is required for its nuclear localization and optimal virus
      multiplication.
AB  - During baculovirus infection, most viral proteins must be imported to the nucleus
      to support virus multiplication. Autographa californica multiple
      nucleopolyhedrovirus (AcMNPV) orf34 (ac34) is an alphabaculovirus unique gene
      that is required for optimal virus production. Ac34 distributes in both the
      cytoplasm and the nuclei of virus-infected Sf9 cells, but contains no
      conventional nuclear localization signal (NLS). In this study, we investigated
      the nuclear targeting domains in Ac34. Transient expression assays showed that
      Ac34 localized in both the cytoplasm and the nuclei of Sf9 cells, indicating that
      no viral protein is required for Ac34 nuclear localization. Subcellular
      localization analysis of Ac34 truncations and internal deletions fused with green
      fluorescent protein in plasmid-transfected Sf9 cells identified that the 91-205
      amino acid (aa) region is required for Ac34 nuclear localization. Mutations in a
      potential C3H zinc finger (aa 116-131) in Ac34 resulted in exclusive cytoplasmic
      distribution of GFP:Ac34, suggesting that the zinc finger is required for Ac34
      nuclear localization. To assess the functional importance of Ac34 in the nucleus
      during virus replication, recombinant AcMNPV bacmids containing a series of Ac34
      truncations, internal deletions, or site mutations fused with HA tags were
      constructed. Subcellular localization analysis showed that Ac34 with internal
      deletions in aa 91-205 or site mutations in the potential zinc finger was
      predominantly distributed in the cytoplasm. Viral plaque assays and virus growth
      curves indicated that disruption of Ac34 nuclear localization significantly
      impaired virus replication. Taken together, our findings demonstrated that the
      nuclear localization of Ac34 requires the 91-205 aa region and its nuclear
      localization is essential for optimal virus replication.

PMID- 27894867
TI  - Creatine kinase as a marker of obesity in a multi-ethnic population.
AB  - OBJECTIVE: Creatine kinase (CK), the central regulatory enzyme of energy
      metabolism, is particularly high in type II skeletal muscle fibers, which are
      associated with insulin resistance and obesity. As resting plasma CK is mainly
      derived from skeletal muscle, we assessed whether plasma CK is associated with
      markers of obesity. METHODS: In this cross-sectional study, we analyzed a random
      sample of the multi-ethnic population of Amsterdam, the Netherlands, consisting
      of 1444 subjects aged 34-60 years. The primary outcome was the independent
      association between plasma CK after rest and waist circumference. Other outcomes
      included waist-to-hip ratio and body mass index. RESULTS: Mean waist
      circumference increased from the first through the third CK tertile, respectively
      90.3 (SD 13.4), 93.2 (SD 14.3), and 94.4 (SD 13.3) cm (p < 0.001 for differences
      between tertiles). The increase in waist circumference was 8.91 (95% CI 5.35 to
      12.47) cm per log CK increase after adjustment for age, sex, African ethnicity,
      educational level, physical activity and plasma creatinine. Similarly, CK was
      independently associated with waist-to-hip ratio and body mass index, with an
      increase of respectively 0.05 (95% CI 0.03 to 0.07) and 3.6 (95% CI 2.3 to 5.0)
      kg/m2 per log CK increase. CONCLUSIONS: Plasma CK is independently associated
      with measures of obesity in a multi-ethnic population. This is in line with the
      central role of type II skeletal muscle fibers in energy metabolism and obesity.
      Prospective studies should assess whether resting plasma CK could be an easy
      accessible marker of CK rich type II fiber predominance that helps identify
      individuals at risk for obesity.

PMID- 27894870
TI  - A benzo[b]thiophene-based selective type 4 S1P receptor agonist.
AB  - S1P receptors (S1PR1-5) are a group of GPCRs activated by a high affinity binding
      with S1P that have important roles in the regulation of the immune system. A
      potent S1PR agonist FTY720 is an immunomodulator used to treat multiple sclerosis
      and several 'second generation' drugs are under clinical development. Subtype
      selective agonists have been reported for each S1PR isotype, some of which are
      used as pharmacological tools for functional studies. Here we report the
      discovery and initial characterization of compound 5c, a benzo[b]thiophene amino
      carboxylate which exhibits potent and selective agonist activity for S1PR4.
      Compound 5c has an EC50=200nM as an agonist in GTPgamma35S binding assay for
      S1PR4 and exhibits no activity against S1PR1,2,3,5. We confirmed its potent
      activity and decent S1PR subtype selectivity using biochemical and cellular
      assays.

PMID- 27894869
TI  - Utilization of alkyne bioconjugations to modulate protein function.
AB  - The ability to introduce or modify protein function has widespread application to
      multiple scientific disciplines. The introduction of unique unnatural amino acids
      represents an excellent mechanism to incorporate new functionality; however, this
      approach is limited by ability of the translational machinery to recognize and
      incorporate the chemical moiety. To overcome this potential limitation, we aimed
      to exploit the functionality of existing unnatural amino acids to perform
      bioorthogonal reactions to introduce the desired protein modification, altering
      its function. Specifically, via the introduction of a terminal alkyne containing
      unnatural amino acid, we demonstrated chemically programmable protein
      modification through the Glaser-Hay coupling to other terminal alkynes, altering
      the function of a protein. In a proof-of-concept experiment, this approach has
      been utilized to modify the fluorescence spectrum of green fluorescent protein.

PMID- 27894871
TI  - Mesoionic pyrido[1,2-a]pyrimidinones: Discovery of triflumezopyrim as a potent
      hopper insecticide1.
AB  - A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with
      exceptional insecticidal activity controlling a number of insect species. In this
      communication, we report the part of the optimization program which led to the
      discovery of triflumezopyrim as a highly potent insecticide controlling various
      hopper species. Our efforts in discovery, synthesis, structure-activity
      relationship elucidation, and biological activity evaluation are also presented.

PMID- 27894872
TI  - Synthesis, screening and docking analysis of hispolon analogs as potential
      antitubercular agents.
AB  - A series of 20 hispolons/dihydrohispolons were synthesized and characterized by
      spectral data. These compounds were subjected to in vitro antitubercular activity
      screening against Mycobacterium tuberculosis (H37Rv) strain. The synthesized
      compounds showed varied antitubercular activity ranging from 100 to 1.6MUg/mL.
      Among the screened compounds, four compounds (H1, H2, H3 and H15) have shown
      moderate activity with MIC 25MUg/mL. Potent activities were observed for the
      dihydrohispolon derivative H14 (MIC 1.6MUg/mL) followed by H13 (6.25MUg/mL) and
      H17 (12.5MUg/mL), H19 (3.125MUg/ML). Docking simulations gave good insights on
      the possible interactions between the tested compounds and beta-keto acyl
      synthase enzyme (mtbFabH). Drug-inhibitor combination studies showed no synergism
      with the drugs targeting mycolic acid biosynthesis (isoniazid, ethambutol and
      thiolactomycin, a specific inhibitor of KAS-B enzyme) but showed significant
      synergism with other drugs including rifampicin and ciprofloxacin ascertaining
      the drug target for hispolons as inhibition of mycolic acid biosynthesis,
      probably via mtbFabH.

PMID- 27894874
TI  - MARK inhibitors: Declaring a No-Go decision on a chemical series based on
      extensive DMPK experimentation.
AB  - Attempts to optimize pharmacokinetic properties in a promising series of
      pyrrolopyrimidinone MARK inhibitors for the treatment of Alzheimer's disease are
      described. A focus on physical properties and ligand efficiency while prosecuting
      this series afforded key tool compounds that revealed a large discrepancy in the
      rat in vitro-in vivo DMPK (Drug Metabolism/Pharmacokinetics) correlation. These
      differences prompted an in vivo rat disposition study employing a radiolabeled
      representative of the series, and the results from this experiment justified the
      termination of any further optimization efforts.

PMID- 27894873
TI  - Design, synthesis and anti-HIV-1 RT evaluation of 2-(benzyl(4-chlorophenyl)amino)
      1-(piperazin-1-yl)ethanone derivatives.
AB  - In this study, using molecular hybridization approach, fourteen novel 2-(benzyl(4
      chlorophenyl)amino)-1-(piperazin-1-yl)ethanone derivatives (7a-n) were designed
      as inhibitor of HIV-1 RT. The binding affinity of the designed compounds with HIV
      1 RT as well as their drug-likeness behavior was predicted using in-silico
      studies. All the designed compounds were synthesized, characterized and in-vitro
      evaluated for HIV-1 RT inhibitory activity, in which tested compounds displayed
      significant to weak potency against the selected target. Moreover, best active
      compounds of the series, 7k and 7m inhibited the activity of RT with IC50 values
      14.18 and 12.26MUM respectively. Structure Activity Relationship (SAR) studies
      were also performed in order to predict the influence of substitution pattern on
      the RT inhibitory potency. Anti-HIV-1 and cytotoxicity studies of best five RT
      inhibitor (7a, 7d, 7k, 7L and 7m) revealed that, except compound 7d other
      compounds retained significant anti-HIV-1 potency with good safety index. Best
      scoring pose of compound 7m was analysed in order to predict its putative binding
      mode with wild HIV-1 RT.

PMID- 27894875
TI  - Effect of bronchodilators in healthy individuals receiving lumacaftor/ivacaftor
      combination therapy.
AB  - In an open-label, single-center phase 1 pharmacokinetic study in healthy subjects
      who received lumacaftor (LUM) in combination with ivacaftor (IVA), review of
      spirometry data showed a transient decline in percent predicted forced expiratory
      volume in 1s (ppFEV1) within 4h of drug administration. An additional cohort of
      healthy subjects with normal baseline ppFEV1 values was studied to evaluate the
      ppFEV1 response to LUM/IVA administration and assess the effect of long-acting
      bronchodilators (LABDs) and short-acting bronchodilators (SABDs) on ppFEV1
      response. The ppFEV1 decline observed at 4h was attenuated following
      administration of an LABD and reversed following administration of an SABD.
      Concomitant administration of LUM/IVA with bronchodilators was well tolerated.
      These data show that a transient decline in ppFEV1 was observed in healthy
      subjects following administration of LUM/IVA combination therapy, which can be
      ameliorated with LABDs or SABDs.

PMID- 27894876
TI  - Long-term functional outcomes after primary surgical repair of acute and chronic
      patellar tendon rupture: Series of 25 patients.
AB  - OBJECTIVE: We aimed to evaluate the clinical outcomes after surgical repair of
      patellar tendon rupture (PTR) and compare the evolution of 2 types of rupture
      (acute and chronic) after the same rehabilitation protocol. METHODS: This was a
      prospective cohort study of patients with PTR treated between January 2006 and
      January 2014 in the department of trauma surgery, Ibn Rochd university hospital,
      Casablanca. RESULTS: We evaluated 25 patients (21 men) after a median follow-up
      of 75 months (range 29-120). The mean age was 34.7+/-8.59 years. Overall, 17
      patients had acute rupture and 8 chronic rupture. Fifteen healthy volunteers (13
      men) were recruited as a control group. Mean Knee Society Score (KSS) knee score
      was significantly higher after than before surgery (82.28+/-12.297 vs 20.64+/
      7.6; P<0.0001) as was KSS function score (88.40+/-17.483 vs 23.40+/-8.98;
      P<0.0001). Pain measured on a visual analog scale was significantly lower after
      than before surgery (1.96+/-1.24 vs 6.60+/-1.26; P<0.0001). ROM and KSS knee and
      function scores were significantly lower on the operated than non-operated side
      after surgery. For both types of PTR, only knee extensor muscle strength was
      significantly lower on the operated than non-operated side and as compared with
      healthy volunteer knees. CONCLUSIONS: Surgical repair of PTR with reinforcement
      and an early rehabilitation program demonstrate good results after a long follow
      up. However, chronic PTR may need longer or a different rehabilitation protocol
      of the knee-extensor apparatus.

PMID- 27894877
TI  - Relief learning requires a coincident activation of dopamine D1 and NMDA
      receptors within the nucleus accumbens.
AB  - Relief learning is the association of a stimulus with the offset of an aversive
      event. Later, the now conditioned relief stimulus induces appetitive-like
      behavioral changes. We previously demonstrated that the NMDA receptors within the
      nucleus accumbens (NAC) are involved in relief learning. The NAC is also
      important for reward learning and it has been shown that reward learning is
      mediated by an interaction of accumbal dopamine and NMDA glutamate receptors.
      Since conditioned relief has reward-like properties, we hypothesized that (a)
      acquisition of relief learning requires the activation of dopamine D1 receptors
      in the NAC, and (b) if D1 receptors are involved in this process as expected, a
      concurrent dopamine D1 and NMDA receptor activation may mediate this learning.
      The present study tested these hypotheses. Therefore, rats received intra-NAC
      injections of the dopamine D1 receptor antagonist SCH23390 and the NMDA
      antagonist AP5, either separately or together, at different time points of a
      relief conditioning procedure. First, we showed that SCH23390 dose-dependently
      blocked acquisition and the expression of conditioned relief. Next, we
      demonstrated that co-injections of SCH23390 and AP5 into the NAC, at doses that
      were ineffective when applied separately, blocked acquisition but not
      consolidation or expression of relief learning. Notably, neither of the
      injections affected the locomotor response of the animals to the aversive stimuli
      suggesting that their perception is not changed. This data indicates that a co
      activation of dopamine D1 and NMDA receptors in the NAC is required for
      acquisition of relief learning.

PMID- 27894879
TI  - Alternating Delays Achieve Polarization Transfer (ADAPT) to heteronuclei in PHIP
      experiments.
AB  - A new methodology for producing hyperpolarized 13C nuclei in small organic
      systems via parahydrogen induced polarization (PHIP) is proposed: ADAPT
      (Alternating Delays Achieve Polarization Transfer). The theoretical foundation of
      the process is investigated in some detail and experimental examples
      demonstrating the viability of the approach are provided as well. The number of
      adjustable parameters is fewer than most of other conversion schemes. The
      achieved theoretical heteronuclear polarization is close to unity for any
      examined magnetic equivalence regime. The duration of the pulse sequence, which
      was successfully implemented, can be shorter than other established methods
      reducing possible relaxation losses. The conversion scheme is robust to B1
      inhomogeneities, but more sensitive to off-resonance RF irradiation.

PMID- 27894880
TI  - Lymphoma of the eyelid.
AB  - Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously
      published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are
      of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone
      lymphoma (27 cases-14%) and diffuse large B-cell lymphoma (18 cases-9%). T-cell
      lymphomas are most frequently mycosis fungoides (25 cases-13%), extranodal
      natural killer/T-cell, nasal-type lymphoma (12 cases-6%), and primary cutaneous
      anaplastic large-cell lymphoma (12 cases-6%). This distribution differs from the
      distribution of ocular adnexal lymphoma and that of cutaneous lymphoma. The
      majority of subtypes occur in elderly patients, except for lymphoblastic lymphoma
      of B-cell and T-cell origin and Burkitt lymphoma, which occur in children and
      adolescents. Several subtypes have a male predominance, including peripheral T
      cell lymphoma and Burkitt lymphoma. Only lymphomatoid papulosis has a female
      predominance. Signs of B-cell and T-cell lymphomas are tumor and swelling of the
      eyelid. Ulceration and erythema occur frequently among patients with T-cell
      lymphoma. Radiotherapy with or without surgery is the treatment of choice for low
      grade, solitary lymphomas, whereas chemotherapy with or without adjuvant
      treatment is the treatment of choice for high-grade or disseminated lymphomas.
      The majority of subtypes, especially low-grade subtypes, have a good prognosis
      with few recurrences or progression. Some subtypes, including mycosis fungoides,
      have a poorer prognosis. Extranodal natural killer/T-cell lymphoma, nasal type
      has an exceedingly poor prognosis.

PMID- 27894878
TI  - Functionally conserved RNA-binding and protein-protein interaction properties of
      LINE-ORF1p in an ancient clade of non-LTR retrotransposons of Entamoeba
      histolytica.
AB  - Retrotransposons are mobile genetic elements found in most organisms. Their
      origin and evolution is not very well understood. Retrotransposons that lack long
      terminal repeats (non-LTR) have been classified based on their reverse
      transcriptase (RT) and endonuclease sequences into groups, of which R2 is the
      most ancient. Its members contain a single open reading frame (ORF) while there
      are two ORFs in the other groups, of which ORF2 contains the RT and endonuclease
      sequences. It is thought that ORF1 was added later to the single-ORF-containing
      elements, and codes for a protein with nucleic acid binding activity. We have
      examined the non-LTR retrotransposons in Entamoeba histolytica, an early
      branching parasitic protist, which belongs to the R2 group. However, unlike other
      members of R2, E. histolytica contains two ORFs. Here we show that EhLINE1-ORF1p
      is functionally related to the ORF1p found in the non-R2 groups. Its N-terminal
      region has RNA-binding activity and its C-terminal has a coiled coil domain which
      participates in protein-protein interaction. It lacks sequence-specificity of RNA
      binding and binds to EhLINE1-RNA fragment and ribosomal RNA with comparable
      affinities. Our study suggests that ORF1p could have evolved independently to
      maintain functional conservation.

PMID- 27894881
TI  - Comparative study of isolation, expansion and characterization of epithelial
      cells.
AB  - BACKGROUND AIMS: The human epithelial cells (EPCs) have been identified as the
      essential element for the regeneration of skin construct for burns, wounds and
      various tissue engineer-based products. METHODS: In this study, the isolation,
      expansion and characterization of EPCs from various sources such as juvenile
      foreskin (JSK), buccal mucosa (BM), penile skin (PS) and urothelium (UR) in serum
      free and xeno-free EpiLife media were evaluated. RESULTS: The growth kinetics
      study revealed that EPCs from JSK and BM had notably higher growth rates compared
      with the others. Overall, the EPCs from all sources retained basic morphological
      characteristics and the functional characteristics such as Pan Cytokeratin
      (AE1/AE3). In addition, the cryopreservation stability of EPCs was accessed for
      post-thaw viability and found to be greater than 80% at 1 year of storage, but
      demonstrated reduced cell recovery (51%) at the second year in fetal bovine serum
      free cryopreservation media. CONCLUSIONS: Our result suggests that the EPCs from
      four cell sources can be grown in feeder-free, serum-free and xeno-free systems
      using commercially available EpiLife medium without losing epithelial cell
      characteristics even after passage 4. However, its suitability for clinical
      application must be accessed by preclinical and clinical studies.

PMID- 27894882
TI  - Comparing biomarker responses during thermal acclimation: A lethal vs non-lethal
      approach in a tropical reef clownfish.
AB  - Knowledge of thermal stress biology for most tropical fish species in reef
      ecosystems under climate change is still quite limited. Thus, the objective of
      this study was to measure the time-course changes of thermal stress biomarkers in
      the commercially exploited coral reef fish Amphiprion ocellaris, during a
      laboratory simulated event of increased temperature. Heat shock protein 70kDa
      (Hsp70) and total ubiquitin (Ub) were determined in the muscle (lethal method)
      and in the fin (non-lethal alternative method) under two temperature treatments
      (control - 26 degrees C and elevated temperature - 30 degrees C) throughout one
      month with weekly samplings. Results suggest that biomarker basal levels are
      tissue-specific and influence the degree of response under temperature exposure.
      Responses were highly inducible in the muscle but not in fin tissue, indicating
      that the latter is not reliable for monitoring purposes. Thermal stress was
      observed in the muscle after one week of exposure (both biomarkers increased
      significantly) and Ub levels then decreased, suggesting the animals were able to
      acclimate by maintaining high levels of Hsp70 and through an effective protein
      turnover. In addition, the results show that mortality rates did not differ
      between treatments. This indicates that A. ocellaris is capable of displaying a
      plastic response to elevated temperature by adjusting the protein quality control
      system to protect cell functions, without decreasing survival. Thus, this coral
      reef fish species presents a significant acclimation potential under ocean
      warming scenarios of +4 degrees C. Monitoring of thermal stress through a non
      lethal method, fin-clipping, although desirable proved to be inadequate for this
      species.

PMID- 27894883
TI  - Incubation relative humidity induces renal morphological and physiological
      remodeling in the embryo of the chicken (Gallus gallus domesticus).
AB  - The metanephric kidneys of the chicken embryo, along with the chorioallantoic
      membrane, process water and ions to maintain osmoregulatory homeostasis. We
      hypothesized that changes in relative humidity (RH) and thus osmotic conditions
      during embryogenesis would alter the developmental trajectory of embryonic kidney
      function. White leghorn chicken eggs were incubated at one of 25-30% relative
      humidity, 55-60% relative humidity, and 85-90% relative humidity. Embryos were
      sampled at days 10, 12, 14, 16, and 18 to examine embryo and kidney mass,
      glomerular characteristics, body fluid osmolalities, hematological properties,
      and whole embryo oxygen consumption. Low and especially high RH elevated
      mortality, which was reflected in a 10-20% lower embryo mass on D18. Low RH
      altered several glomerular characteristics by day 18, including increased numbers
      of glomeruli per kidney, increased glomerular perfusion, and increased total
      glomerular volume, all indicating potentially increased functional kidney
      capacity. Hematological variables and plasma and amniotic fluid osmolalities
      remained within normal physiological values. However, the allantoic, amniotic and
      cloacal fluids had a significant increase in osmolality at most developmental
      points sampled. Embryonic oxygen consumption increased relative to control at
      both low and high relative humidities on Day 18, reflecting the increased
      metabolic costs of osmotic stress. Major differences in both renal structure and
      performance associated with changes in incubation humidity occurred after
      establishment of the metanephric kidney and persisted into late development, and
      likely into the postnatal period. These data indicate that the avian embryo
      deserves to be further investigated as a promising model for fetal programming of
      osmoregulatory function, and renal remodeling during osmotic stress.

PMID- 27894884
TI  - Modulation of the heat shock response is associated with acclimation to novel
      temperatures but not adaptation to climatic variation in the ants Aphaenogaster
      picea and A. rudis.
AB  - Ecological diversification into thermally divergent habitats can push species
      toward their physiological limits, requiring them to accommodate temperature
      extremes through plastic or evolutionary changes that increase persistence under
      the local thermal regime. One way to withstand thermal stress is to increase
      production of heat shock proteins, either by maintaining higher baseline
      abundance within cells or by increasing the magnitude of induction in response to
      heat stress. We evaluated whether environmental variation was associated with
      expression of three heat shock protein genes in two closely-related species of
      woodland ant, Aphaenogaster picea and A. rudis. We compared adult workers from
      colonies collected from 25 sites across their geographic ranges. Colonies were
      maintained at two different laboratory temperatures, and tested for the
      independent effects of environment, phylogeny, and acclimation temperature on
      baseline and heat-induced gene expression. The annual maximum temperature at each
      collection site (Tmax) was not a significant predictor of either baseline
      expression or magnitude of induction of any of the heat shock protein genes
      tested. A phylogenetic effect was detected only for basal expression of Hsp40,
      which was lower in the most southern populations of A. rudis and higher in a mid
      range population of possible hybrid ancestry. In contrast, a higher acclimation
      temperature significantly increased baseline expression of Hsc70-4, and increased
      induction of Hsp40 and Hsp83. Thus, physiological acclimation to temperature
      variation appears to involve modulation of the heat shock response, whereas other
      mechanisms are likely to be responsible for evolutionary shifts in thermal
      performance associated with large-scale climate gradients.

PMID- 27894885
TI  - Metabolic rates are elevated and influenced by maternal identity during the
      early, yolk-dependent, post-hatching period in an estuarine turtle, the
      diamondback terrapin (Malaclemys terrapin).
AB  - Non-genetic maternal effects, operating through a female's physiology or
      behavior, can influence offspring traits and performance. Here we examined
      potential maternal influences on metabolic rates (MR) of offspring in an
      estuarine turtle, the diamondback terrapin (Malaclemys terrapin). Females and
      their eggs were collected from the field and the eggs incubated in the laboratory
      for subsequent measurement of MR of females, late-stage embryos, newly-hatched
      individuals that were nutritionally dependent on yolk, and older hatchlings that
      had depleted their yolk reserves and thus were independent of energetic
      contributions from the female. Female identity significantly affected MR of yolk
      dependent hatchlings but, after yolk was depleted, MR of offspring converged and
      no longer reflected the maternal influence. Offspring from different females also
      differed in size, which influenced offspring MR and growth, but there was no
      correlation between female MR or size and offspring traits. MR of the older, yolk
      independent hatchlings was lower overall than yolk-dependent hatchlings but
      correlated positively with growth rates and prior developmental rate (e.g.
      negatively correlated with time to hatching). Unlike another turtle species
      (snapping turtles), in which maternally-related differences in offspring MR were
      retained after yolk depletion, the maternal influence on offspring MR in
      diamondback terrapins is limited to early hatchling development and growth. The
      transient nature of the maternal effect, which was present only during the period
      that hatchlings were metabolizing yolk, suggests that variation among females in
      the composition of yolk deposited in eggs could be responsible for the
      differences observed in this study.

PMID- 27894886
TI  - Utility of Urgent Computed Tomography Angiography in the Setting of
      Intraparenchymal Brain Hemorrhage.
AB  - BACKGROUND AND PURPOSE: Patients presenting with an intracerebral hemorrhage
      (ICH) generally have an initial noncontrast computed tomography (NCCT) of the
      brain. Computed tomography angiography (CTA) can help identify secondary causes
      of ICH and detect a "spot sign." We hypothesized that performing an urgent CTA in
      the setting of a presumed primary ICH has only limited utility and did not alter
      urgent management. METHODS: This was a retrospective study of consecutive
      patients presenting with a primary ICH identified from the Duke University Stroke
      Registry from 2010 to 2013 who had an ICH detected on an initial NCCT. Patients
      with hemorrhages related to tumor, hemorrhagic conversion of an ischemic stroke,
      and known secondary causes were excluded. CTA within the first 10 hours of
      presentation was considered "urgent." RESULTS: Of 246 patients meeting the
      inclusion criteria, 53% had an urgent CTA. Those who underwent a CTA were younger
      (61 +/- 1 versus 70 +/- 1 years, P < .0001) and more commonly had deep bleeds
      (50% versus 45%, P = .048). CTA identified 12 aneurysms (10 incidental) and 2
      arteriovenous malformations; 87% were normal. Urgent CTA was associated with a
      change in management in 3 cases (2.2%); each had historic or other findings
      suggestive of a secondary cause of hemorrhage and none led to urgent treatment
      changes. CONCLUSIONS: In the absence of features suggesting a secondary cause,
      the results of an urgent CTA did not alter the urgent management of a consecutive
      series of patients with ICH. CTAs may be safely delayed until after the acute
      period in these patients.

PMID- 27894887
TI  - Ultrasound Tissue Pulsatility Imaging Suggests Impairment in Global Brain
      Pulsatility and Small Vessels in Elderly Patients with Orthostatic Hypotension.
AB  - BACKGROUND: Orthostatic hypotension (OH) is highly prevalent in the elderly, and
      this population can be exposed to serious complications, including falls and
      cognitive disorders, as well as overall mortality. However, the pathophysiology
      of OH is still poorly understood, and innovative methods of cerebral blood flow
      (CBF) assessment have been required to accurately investigate cerebrovascular
      reactivity in OH. OBJECTIVES: We want to compare brain tissue pulsatility (BTP)
      changes during an orthostatic challenge in elderly patients over 80 with and
      without OH. MATERIALS AND METHODS: Forty-two subjects aged 80 and over were
      recruited from the geriatric unit of the Hospital of Tours, France, and were
      divided into two groups according to the result of an orthostatic challenge. The
      noninclusion criteria were any general unstable medical condition incompatible
      with orthostatic challenge, having no temporal acoustic window, severe cognitive
      impairment (Mini Mental Status Examination <15), history of stroke, and legal
      guardianship. We used the novel and highly sensitive ultrasound technique of
      tissue pulsatility imaging to measure BTP changes in elderly patients with (n =
      22) and without OH (n = 17) during an orthostatic challenge. RESULTS: We found
      that the mean brain tissue pulsatility related to global intracranial
      pulsatility, but not maximum brain tissue pulsatility related to large arteries
      pulsatility, decreased significantly in OH patients, with a delay compared with
      the immediate drop in peripheral blood pressure. CONCLUSION: Global pulsatile CBF
      changes and small vessels pulsatility, rather than changes in only large
      arteries, may be key mechanisms in OH to account for the links between OH and
      cerebrovascular disorders.

PMID- 27894888
TI  - Excessive Premature Atrial Complexes and the Risk of Recurrent Stroke or Death in
      an Ischemic Stroke Population.
AB  - BACKGROUND: Our aim was to investigate the association of premature atrial
      complexes and the risk of recurrent stroke or death in patients with ischemic
      stroke in sinus rhythm. METHODS: In a prospective cohort study, we used 24-hour
      Holter recordings to evaluate premature atrial complexes in patients
      consecutively admitted with ischemic strokes. Excessive premature atrial
      complexes were defined as >14 premature atrial complexes per hour and 3 or more
      runs of premature atrial complexes per 24 hours. During follow-up, 48-hour Holter
      recordings were performed after 6 and 12 months. Among patients in sinus rhythm,
      the association of excessive premature atrial complexes and the primary end point
      of recurrent stroke or death were estimated in both crude and adjusted Cox
      proportional hazards models. We further evaluated excessive premature atrial
      complexes contra atrial fibrillation in relation to the primary end point.
      RESULTS: Of the 256 patients included, 89 had atrial fibrillation. Of the
      patients in sinus rhythm (n = 167), 31 had excessive premature atrial complexes.
      During a median follow-up of 32 months, 50 patients (30% of patients in sinus
      rhythm) had recurrent strokes (n = 20) or died (n = 30). In both crude and
      adjusted models, excessive premature atrial complexes were associated with the
      primary end point, but not with newly diagnosed atrial fibrillation. Compared
      with patients in atrial fibrillation, those with excessive premature atrial
      complexes had similarly high risks of the primary end point. CONCLUSIONS: In
      patients with ischemic stroke and sinus rhythm, excessive premature atrial
      complexes were associated with a higher risk of recurrent stroke or death.

PMID- 27894891
TI  - Source analysis of auditory steady-state responses in acoustic and electric
      hearing.
AB  - Speech is a complex signal containing a broad variety of acoustic information.
      For accurate speech reception, the listener must perceive modulations over a
      range of envelope frequencies. Perception of these modulations is particularly
      important for cochlear implant (CI) users, as all commercial devices use envelope
      coding strategies. Prolonged deafness affects the auditory pathway. However,
      little is known of how cochlear implantation affects the neural processing of
      modulated stimuli. This study investigates and contrasts the neural processing of
      envelope rate modulated signals in acoustic and CI listeners. Auditory steady
      state responses (ASSRs) are used to study the neural processing of amplitude
      modulated (AM) signals. A beamforming technique is applied to determine the
      increase in neural activity relative to a control condition, with particular
      attention paid to defining the accuracy and precision of this technique relative
      to other tomographies. In a cohort of 44 acoustic listeners, the location,
      activity and hemispheric lateralisation of ASSRs is characterised while
      systematically varying the modulation rate (4, 10, 20, 40 and 80Hz) and
      stimulation ear (right, left and bilateral). We demonstrate a complex pattern of
      laterality depending on both modulation rate and stimulation ear that is
      consistent with, and extends, existing literature. We present a novel extension
      to the beamforming method which facilitates source analysis of electrically
      evoked auditory steady-state responses (EASSRs). In a cohort of 5 right implanted
      unilateral CI users, the neural activity is determined for the 40Hz rate and
      compared to the acoustic cohort. Results indicate that CI users activate typical
      thalamic locations for 40Hz stimuli. However, complementary to studies of
      transient stimuli, the CI population has atypical hemispheric laterality,
      preferentially activating the contralateral hemisphere.

PMID- 27894890
TI  - Convergent individual differences in visual cortices, but not the amygdala across
      standard amygdalar fMRI probe tasks.
AB  - : The amygdala (AMG) has been repeatedly implicated in the processing of
      threatening and negatively valenced stimuli and multiple fMRI paradigms have
      reported personality, genetic, and psychopathological associations with
      individual differences in AMG activation in these paradigms. Yet the
      interchangeability of activations in these probes has not been established, thus
      it remains unclear if we can interpret AMG responses on specific tasks as general
      markers of its reactivity. In this study we aimed to assess if different tasks
      that have been widely used within the Affective Neuroscience literature
      consistently recruit the AMG. METHOD: Thirty-two young healthy subjects completed
      four fMRI tasks that have all been previously shown to probe the AMG during
      processing of threatening stimuli: the Threat Face Matching (TFM), the Cued
      Aversive Picture (CAP), the Aversive and Erotica Pictures (AEP) and the Screaming
      Lady paradigm (SLp) tasks. Contrasts testing response to aversive stimuli
      relative to baseline or neutral stimuli were generated and correlations between
      activations in the AMG were calculated across tasks were performed for ROIs of
      the AMG. RESULTS: The TFM, CAP and AEP, but not the SLp, successfully recruit the
      AMG, among other brain regions, especially when contrasts were against baseline
      or nonsocial stimuli. Conjunction analysis across contrasts showed that visual
      cortices (VisCtx) were also consistently recruited. Correlation analysis between
      the extracted data for right and left AMG did not yield significant associations
      across tasks. By contrast, the extracted signal in VisCtx showed significant
      associations across tasks (range r=0.511-r=0.630). CONCLUSIONS: Three of the four
      paradigms revealed significant AMG reactivity, but individual differences in the
      magnitudes of AMG reactivity were not correlated across paradigms. By contrast,
      VisCtx activation appears to be a better candidate than the AMG as a measure of
      individual differences with convergent validity across negative emotion
      processing paradigms.

PMID- 27894892
TI  - Longitudinal functional brain imaging study in early course schizophrenia before
      and after cognitive enhancement therapy.
AB  - OBJECTIVE: Schizophrenia is characterized by impaired -social and non social
      cognition both of which lead to functional deficits. These deficits may benefit
      from cognitive remediation, but the neural underpinnings of such improvements
      have not been clearly delineated. METHODS: We conducted a functional magnetic
      resonance (fMRI) study in early course schizophrenia patients randomly assigned
      to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and
      treated for two years. Imaging data over three time points including fMRI blood
      oxygen level dependent (BOLD) data were acquired during performance of a
      cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and
      functional connectivity data, were analyzed. RESULTS: During the two years of
      treatment, CET patients showed a continual increase in BOLD activity in the right
      dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no
      change in prefrontal brain function throughout treatment. Increases in right
      DLPFC activity were modestly associated with improved neurocognition (beta = .14,
      p = .041), but not social cognition. Functional connectivity analyses showed
      reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in
      CET compared to EST over the two years of treatment, which was associated with
      neurocognitive improvement. CONCLUSIONS: These findings suggest that CET leads to
      enhanced neural activity in brain regions mediating cognitive control and
      increased efficiency in prefrontal circuits; such changes may be related to the
      observed therapeutic effects of CET on neurocognitive function.

PMID- 27894889
TI  - Tradeoffs in pushing the spatial resolution of fMRI for the 7T Human Connectome
      Project.
AB  - Whole-brain functional magnetic resonance imaging (fMRI), in conjunction with
      multiband acceleration, has played an important role in mapping the functional
      connectivity throughout the entire brain with both high temporal and spatial
      resolution. Ultrahigh magnetic field strengths (7T and above) allow functional
      imaging with even higher functional contrast-to-noise ratios for improved spatial
      resolution and specificity compared to traditional field strengths (1.5T and 3T).
      High-resolution 7T fMRI, however, has primarily been constrained to smaller brain
      regions given the amount of time it takes to acquire the number of slices
      necessary for high resolution whole brain imaging. Here we evaluate a range of
      whole-brain high-resolution resting state fMRI protocols (0.9, 1.25, 1.5, 1.6 and
      2mm isotropic voxels) at 7T, obtained with both in-plane and slice acceleration
      parallel imaging techniques to maintain the temporal resolution and brain
      coverage typically acquired at 3T. Using the processing pipeline developed by the
      Human Connectome Project, we demonstrate that high resolution images acquired at
      7T provide increased functional contrast to noise ratios with significantly less
      partial volume effects and more distinct spatial features, potentially allowing
      for robust individual subject parcellations and descriptions of fine-scaled
      patterns, such as visuotopic organization.

PMID- 27894893
TI  - The blood brain barrier in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia, affecting millions
      of people worldwide. One of the prominent causative factors of AD pathogenesis is
      cerebral vascular dysfunction, which results in diminished cerebral perfusion.
      Moreover, due to the loss of the protective function of the blood-brain barrier
      (BBB), impaired clearance of excess neurotoxic amyloid beta (Abeta) occurs,
      causing vascular perturbation and diminished cognitive functioning. The
      relationship between the prevalence of AD and vascular risk factors is complex
      and not fully understood. In this review we illustrate the vascular risk factors,
      their effects on BBB function and their contributions to the onset of AD.
      Additionally, we discuss the underlying factors that may lead to altered
      neurovascular function and/or cerebral hypoperfusion in AD.

PMID- 27894894
TI  - Junctional zone thickness in young nulliparous women according to menstrual cycle
      and hormonal contraception use.
AB  - This prospective study aims to determine the optimal menstrual phase and uterine
      location to detect the thickest junctional zone by magnetic resonance imaging
      (MRI). Healthy nulliparous women were subdivided according to their use of
      hormonal contraception. Each women was investigated three times during their
      menstrual cycle. Eighteen nulliparous non-users and 29 nulliparous users of
      hormonal contraception (mean age 26.4 and 25.8 years, respectively) underwent a
      pelvic MRI (1.5T) examination during the follicular, ovulatory and luteal phase.
      The junctional zone thickness was measured at six locations in the uterine wall.
      A significantly thinner junctional zone was observed at the anterior and
      posterior wall of the midcorpus (P = 0.01 and P = 0.004 respectively) and fundus
      (P = 0.009 and P = 0.023 respectively), in the contraception users compared with
      the non-users. No differences in junctional zone thickness were noticed between
      the menstrual phases and the uterine wall locations. The ratio of junctional zone
      versus total myometrial thickness was also different between both groups and
      between the assessed uterine locations. To conclude, any phase in the menstrual
      cycle and location within the uterine wall was validated to determine the
      junctional zone thickness on MRI, although the fundal location is preferred.

PMID- 27894895
TI  - Molecular characterization and expression analysis of olive flounder
      (Paralichthys olivaceus) phospholipase C gamma 1 and gamma 2.
AB  - Phospholipase C gamma 1 and gamma 2 (PLCG1 and PLCG2) are influential in
      modulating Ca2+ and diacylglycerol, second messengers involved in tyrosine kinase
      dependent signaling, including growth factor activation. Here, we used RACE
      (rapid amplification of cDNA ends) to clone cDNA encoding PLCG1 (PoPLCG1) and
      PLCG2 (PoPLCG2) in the olive flounder (Paralichthys olivaceus). The respective
      1313 and 1249 amino acid sequences share high identity with human PLCG1 and
      PLCG2, and contain the following domains: pleckstrin homology (PH), EF-hand,
      catalytic X and Y, Src homology 2 (SH2), Src homology 3 (SH3), and C2. Phylogenic
      analysis and sequence comparison of PoPLCG1 and PoPLCG2 with other PLC isozymes
      showed a close relationship between the two PLCGs, supported by structural
      analysis. In addition, tissue expression analysis showed that PoPLCG1 was
      expressed predominantly in the brain, eye, and heart, whereas PoPLCG2 was
      expressed principally in gills, esophagus, spleen, and kidney. Following
      stimulation with LPS and Poly I:C, PoPLCG expression was compared with the
      expression of inflammatory cytokines IL-1beta, IL-6, and TNF-alpha via reverse
      transcription-PCR and real-time quantitative PCR. Our results suggest that PoPLCG
      isozymes perform a critical immune function in olive flounder, being active in
      pathogen resistance and the inflammation process.

PMID- 27894896
TI  - Systematic Review and Meta-analysis of Dual Versus Single Antiplatelet Therapy in
      Carotid Interventions.
AB  - BACKGROUND: The importance of antiplatelet therapy for the management and
      prevention of ischaemic stroke cannot be overstated. Despite the established
      guidelines, there is no clear consensus on how to manage antiplatelet therapy
      during and after carotid interventions. OBJECTIVE: The objective was to undertake
      a systematic literature review and perform a meta-analysis to assess the effects
      of dual antiplatelet therapy in carotid endarterectomy (CEA) and stenting (CAS).
      DATA SOURCES: Electronic information sources (MEDLINE, EMBASE, CINAHL, CENTRAL)
      and bibliographic reference lists were searched to identify randomised controlled
      trials (RCTs) and observational studies reporting comparative outcomes of dual
      versus single antiplatelet therapy in CEA and CAS. METHODS: Primary outcomes were
      mortality and stroke within 30 days of intervention. Secondary outcomes were
      transient ischaemic attack (TIA), major bleeding, groin or neck haematoma, and
      myocardial infarction (MI). Dichotomous outcome measures were reported using the
      risk difference (RD) and 95% confidence interval (CI). Combined overall treatment
      effects were calculated using fixed-effect or random-effects models. RESULTS:
      Three RCTs and seven observational studies were identified reporting a total of
      36,881 CEAs and 150 CAS procedures. In CEA, there were no differences in
      stroke/TIA/death between single and dual antiplatelet therapy, but there was a
      significant risk of major bleeding (RD, 0.00; 95% CI, 0.00-0.01; p = .0003) and
      neck haematoma with dual therapy (RD, 0.04; 95% CI, 0.01-0.06; p = .001). In
      addition, the rate of MI was higher in the dual therapy group than the single
      therapy group (RD, 0.00; 95% CI, 0.00-0.01; p = .003). In CAS, there was no
      difference in major bleeding or haematoma formation, but a significant difference
      in TIA in favour of dual therapy was identified (RD -0.13, 95% CI, -0.22 to 
      0.05; p = .003). CONCLUSIONS: Dual antiplatelet therapy demonstrates advantages
      over single therapy only in CAS, as indicated by a reduced risk of TIA. Dual
      antiplatelet therapy was associated with an increased risk of bleeding
      complications in patients undergoing CEA.

PMID- 27894897
TI  - The Long-term Durability of Intra-operatively Placed Palmaz Stents for the
      Treatment of Type Ia Endoleaks After EVAR of Abdominal Aortic Aneurysm.
AB  - OBJECTIVE/BACKGROUND: The objective was to analyze the long-term durability of
      intra-operatively placed Palmaz stents for type Ia endoleaks, and the evolution
      of aneurysm neck morphology. METHODS: This was a retrospective cohort study
      conducted at a tertiary referral centre. Patients treated between 1998 and 2012
      were reviewed with regard to pre-, intra-, and post-operative data. Crude and
      relative survival estimates were calculated, with the latter referring only to
      patients with >= 3 months' follow-up. RESULTS: In total, 125 patients were
      included (83 elective, 22 ruptures, 20 symptomatic). Nine patients died
      perioperatively (two elective, seven acute). Median follow-up was 43 months
      (range 15-72). Seven patients had late abdominal aortic aneurysm related deaths.
      There were 51 re-interventions (seven type Ia endoleak related). Five year crude
      primary, primary assisted, and secondary success rates were 55 +/- 5%, 66 +/- 5%,
      and 70 +/- 5%, respectively. These crude rates were superior for elective
      patients (p = .008, p = .031, and p = .037, respectively), but the relative rates
      were not (p = .187, p = .640, p = .558, respectively). Primary and assisted
      freedom from type Ia endoleak 5 years post-operatively were 84 +/- 4% and 89 +/-
      3%, respectively. These rates were superior in elective patients (p = .066 and p
      = .145, respectively), especially when relative rates were analysed (p = .025 and
      p = .063, respectively). The visceral aortic diameter increased significantly
      between the first and the last post-operative imaging in 15/91 (16%), 12/91
      (13%), 34/91 (37%), and 30/91 (33%) patients at the levels of coeliac trunk,
      superior mesenteric artery, lowest renal artery, and 9 mm distal to lowest renal
      artery, respectively. CONCLUSION: Intra-operatively placed Palmaz stents confer
      high long-term freedom from type Ia endoleak. Palmaz stents are an acceptable
      intra-operative bailout tool in the acute setting, but should not be used to
      extend elective infrarenal endovascular aneurysm repair to more demanding
      anatomies.

PMID- 27894898
TI  - Inflammatory Changes of the Thoraco-abdominal Aorta.

PMID- 27894900
TI  - Neuroimaging somatosensory perception and masking.
AB  - The specific cortical and subcortical regions involved in conscious perception
      and masking are uncertain. This study sought to identify brain areas involved in
      conscious perception of somatosensory stimuli during a masking task using
      functional magnetic resonance (fMRI) to contrast perceived vs. non-perceived
      targets. Electrical trains were delivered to the right index finger for targets
      and to the left index finger for masks. Target intensities were adjusted to
      compensate for threshold drift. Sham target trials were given in ~10% of the
      trials, and target stimuli without masks were delivered in one of the five runs
      (68 trials/run). When healthy dextral adult volunteers (n=15) perceived right
      hand targets, greater left- than right-cerebral activations were seen with
      similar patterns across the parietal cortex, thalamus, insula, claustrum, and
      midbrain. When targets were not perceived, left/right cerebral activations were
      similar overall. Directly comparing perceived vs. non-perceived stimuli with
      similar intensities in the masking task revealed predominate activations
      contralateral to masks. In contrast, activations were greater contralateral to
      perceived targets if no masks were given or if masks were given but target
      stimulus intensities were greater for perceived than non-perceived targets. The
      novel aspects of this study include: 1) imaging of cortical and subcortical
      activations in healthy humans related to somatosensory perception during a
      masking task, 2) activations in the human thalamus and midbrain related to
      perception of stimuli compared to matched non-perceived stimuli, and 3) similar
      left/right cerebral activation patterns across cortical, thalamic and midbrain
      structures suggesting interactions across all three levels during conscious
      perception in humans.

PMID- 27894899
TI  - Dietary flax seed oil and/or Vitamin E improve sperm parameters of cloned goats
      following freezing-thawing.
AB  - Semen cryopreservation is affected by individual differences and use of clones
      animal from the same source is the main tool to eliminate genetic variation.
      Among many nutrients that are necessary for fertility, essential fatty acids and
      antioxidants are vital for production of healthy sperm by improving sperm
      membrane integrity and protecting sperm from oxidative stress. The goal of the
      current study was to investigate whether a flax seed oil or/and Vitamin E dietary
      supplementation could improve semen quality of cloned bucks following semen
      cryopreservation. Accordingly, eight adult cloned Bakhtiari bucks were divided
      randomly into four groups. Bucks were offered a base diet of hay and concentrate.
      The concentrate was enriched with flax seed oil, 30 gr/kg body weight/day (OIL),
      Vitamin E (VIT), 3 gr/kg body weight/day, or combined flax seed oil and the
      vitamin E (OIL-VIT). The concentrate with no supplements was considered as
      control group (CONT). Both flax seed oil and Vitamin E supplements were added to
      the total diet. The bucks were fed with their corresponding diets for a total of
      9 weeks while sperm collection was carried out within 10-14 weeks. Ejaculates
      were diluted with Andromed(r) and were frozen in liquid nitrogen. Sperm
      parameters and reactive oxygen species (ROS) contents were evaluated following
      freezing/thawing. According to the results of our study, dietary supplementation
      with flax seed oil, or/and Vitamin E can improve sperm motility, vitality and
      number of sperm with intact plasma membrane following freezing-thawing. But the
      degree of improvement in these parameters was significantly higher when Flax seed
      oil and vitamin E were co-supplemented.

PMID- 27894901
TI  - Bilingualism yields language-specific plasticity in left hemisphere's circuitry
      for learning to read in young children.
AB  - How does bilingual exposure impact children's neural circuitry for learning to
      read? Theories of bilingualism suggests that exposure to two languages may yield
      a functional and neuroanatomical adaptation to support the learning of two
      languages (Klein et al., 2014). To test the hypothesis that this neural
      adaptation may vary as a function of structural and orthographic characteristics
      of bilinguals' two languages, we compared Spanish-English and French-English
      bilingual children, and English monolingual children, using functional Near
      Infrared Spectroscopy neuroimaging (fNIRS, ages 6-10, N =26). Spanish offers
      consistent sound-to-print correspondences ("phonologically transparent" or
      "shallow"); such correspondences are more opaque in French and even more opaque
      in English (which has both transparent and "phonologically opaque" or "deep"
      correspondences). Consistent with our hypothesis, both French- and Spanish
      English bilinguals showed hyperactivation in left posterior temporal regions
      associated with direct sound-to-print phonological analyses and hypoactivation in
      left frontal regions associated with assembled phonology analyses. Spanish, but
      not French, bilinguals showed a similar effect when reading Irregular words. The
      findings inform theories of bilingual and cross-linguistic literacy acquisition
      by suggesting that structural characteristics of bilinguals' two languages and
      their orthographies have a significant impact on children's neuro-cognitive
      architecture for learning to read.

PMID- 27894902
TI  - The feasibility of Forward-projected model-based Iterative Reconstruction
      SoluTion (FIRST) for coronary 320-row computed tomography angiography: A pilot
      study.
AB  - BACKGROUND: We aimed to assess and compare the influence of Forward projected
      model-based Iterative Reconstruction SoluTion (FIRST), a recently introduced full
      iterative reconstruction method, on radiation doses and image quality with that
      of Adaptive Iterative Dose Reduction (AIDR) 3D for 320-row cardiac computed
      tomography (CT). METHODS: A total of 184 patients subjected to single-beat
      reconstruction cardiac CT were retrospectively included. The first 89 patients
      received standard radiation doses; their data were reconstructed using AIDR 3D,
      whereas the last 95 patients received in average 20% reduction in tube current;
      their data were reconstructed using FIRST. Subjective image quality (blooming,
      image sharpness, image noise, and overall subjective image quality) were graded
      using 3-, 5-, 4-, and 4-point scales (0-2, 1-5, 1-4, and 1-4), respectively; for
      all items, the highest score indicated excellent image quality. Image noise and
      signal-to-noise ratios at proximal segments were analyzed as objective measures
      of image quality. RESULTS: FIRST reconstruction allowed 28% dose reduction
      compared with AIDR 3D (1.88 vs. 2.61 mSv, p = 0.012) and yielded better
      subjective image quality in terms of blooming, image sharpness, image noise, and
      overall image quality (1.10 vs. 1.01, p = 0.0007; 3.02 vs. 2.74, p < 0.0001; 3.61
      vs. 3.17, p < 0.0001; and 3.30 vs. 2.98, p < 0.0001, respectively). Although no
      significant difference was observed in image noise, the signal-to-noise ratio was
      significantly higher with FIRST (18.4 vs. 16.6, p = 0.0066). CONCLUSIONS: FIRST
      allowed 28% dose reduction while improving image quality.

PMID- 27894903
TI  - Structural basis of accurate replication beyond a bulky major benzo[a]pyrene
      adduct by human DNA polymerase kappa.
AB  - Human Y-family DNA polymerase kappa (polkappa) is specialized to bypass bulky
      lesions in DNA in an error-free way, thus protecting cells from carcinogenic
      bulky DNA adducts. Benzo[a]pyrene (BP) is one of the most ubiquitous polycyclic
      aromatic hydrocarbons and an environmental carcinogen. BP covalently modifies DNA
      and generates mutagenic, bulky adducts. The major BP adduct formed in cells is
      10S (+)-trans-anti-BP-N2-dG adduct (BP-dG), which is associated with cancer. The
      molecular mechanism of how polkappa replicates BP-dG accurately is not clear.
      Here we report the structure of polkappa captured at the lesion-extension stage:
      the enzyme is extending the primer strand after the base pair containing the BP
      dG adduct in the template strand at the -1 position. Polkappa accommodates the BP
      adduct in the nascent DNA's minor groove and keeps the adducted DNA helix in a B
      form. Two water molecules cover the edge of the minor groove of the replicating
      base pair (0 position), which is secured by the BP ring in the -1 position in a
      5' orientation. The 5' oriented BP adduct keeps correct Watson-Crick base pairing
      in the active site and promotes high fidelity replication. Our structural and
      biochemical data reveal a unique molecular basis for accurate DNA replication
      right after the bulky lesion BP-dG.

PMID- 27894904
TI  - From niche to stigma-Headshops to prison: Exploring the rise and fall of
      synthetic cannabinoid use among young adults.
AB  - The aim of this paper will be to consider the rise and subsequent fall in NPS use
      at national and local level with a focus on synthetic cannabinoid products in
      Kent. We will examine the local practice and policy responses by Kent's Young
      Persons' Drug and Alcohol Service towards a possible change in patterns of NPS
      drug consumption. The county has seen an expansion in the number of Headshops and
      we present local media coverage on NPS, and the Trading Standards and Kent Police
      intervention Operation Lantern to regulate Headshops. Through quantitative and
      qualitative data sets on socially vulnerable young people and prison populations
      we explore young adults' perception of pleasure and harm in the use of NPS.
      Emergent data suggests young adults are now assessing the differences between NPS
      and more traditional illicit drugs, with this impacting on decision-making about
      the substances being used. When 'legal highs' first appeared they were associated
      with a more niche middle class demographic, 'psychonauts' and experimental users
      interested in pursuing recreational drug diversity. We examine macro and micro
      data to suggest that populations most likely to become involved in NPS use are
      those with degrees of stigma linked to socially vulnerable young adults
      suggesting that Spice is no longer a feature of middle class recreational drug
      use.

PMID- 27894905
TI  - Racemic alkaloids from the fungus Ganoderma cochlear.
AB  - Seven pairs of new alkaloid enantiomers, ganocochlearines C-I (1, 3-8), and three
      pairs of known alkaloids were isolated from the fruiting bodies of Ganoderma
      cochlear. The chemical structures of new compounds were elucidated on the basis
      of 1D and 2D NMR data. The absolute configurations of compounds 1, 3-10 were
      assigned by ECD calculations. Biological activities of these isolates against
      renal fibrosis were accessed in rat normal or diseased renal interstitial
      fibroblast cells. Importantly, the plausible biosynthetic pathway for this class
      of alkaloids was originally proposed.

PMID- 27894906
TI  - Relationship between NR1I2 polymorphisms and inflammatory bowel disease risk: A
      systematic review and meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Inconsistent results regarding an association between
      polymorphisms within the Homo sapiens nuclear receptor subfamily 1 group I member
      2 (NR1I2) gene and susceptibility to inflammatory bowel disease (IBD) have been
      reported. A systematic review and meta-analysis was thus undertaken to determine
      whether NR1I2 gene polymorphisms are associated with an increased risk of IBD.
      METHODS: Article retrieval was performed using on-line databases, such as PubMed,
      Embase, CENTRAL, and WOS. After extracting eligible data, Mantel-Haenszel
      statistics were applied to calculate the odds radio (OR), 95% confidence interval
      (95% CI) and P value under a random or fixed-effects model. RESULTS: A total of
      seven articles with 4410 IBD subjects and 4028 controls were included. Compared
      with the control group, no significant increase in IBD susceptibility was
      observed for the -25385C/T (OR=0.92, 95% CI=0.78~1.07, P=0.259), -24381A/C
      (OR=0.96, 95% CI=0.87~1.06, P=0.378), +8055C/T (OR=1.06, 95% CI=0.97~1.15,
      P=0.186), or +7635A/G (OR=0.96, 95% CI=0.87~1.05, P=0.348) polymorphisms within
      the NR1I2 gene under the allele model. CONCLUSIONS: Our meta-analysis failed to
      demonstrate an association between -25385C/T, -24381A/C, +8055C/T, or +7635A/G
      polymorphisms within the NR1I2 gene and overall IBD risk. A larger sample size is
      needed to validate our conclusion.

PMID- 27894908
TI  - Implication of artemisinin nematocidal activity on experimental trichinellosis:
      In vitro and in vivo studies.
AB  - Benzimidazole drugs are used for treatment of trichinellosis, but they have a
      limited effect against encapsulated larval stages of Trichinella spiralis. Hence,
      there is a considerable interest in developing new anthelmintic drugs. Our aim is
      to investigate the possible effect of artemisinin on T. spiralis in in vitro and
      in vivo studies. T. spiralis worms were isolated from infected mice and
      transferred to 3 culture media; group I: with no drugs, group II: contained
      artemisinin and group III: contained mebendazole, then they were subjected to
      electron microscopic study. An in vivo study was done where mice were divided
      into three groups; group I: infected and untreated, group II: received
      artemisinin and group III: received mebendazole. The efficacy of treatment was
      assessed by adult and total larval counts, histopathological study of the small
      intestinal and muscle tissues and immunohistochemical staining of cyclooxygenase
      2 (COX-2) and vascular endothelial growth factor (VEGF) in muscles. Adult worm
      teguments showed significant degeneration and destruction with both drugs. Also,
      significant reduction of total adult and larval counts occurred in treated groups
      in comparison to the control group. Histopathological examination of the small
      intestine and muscles showed marked improvement with reduction in the
      inflammatory infiltrates with both drugs. COX-2 and VEGF expressions were reduced
      in both treated groups with more reduction in the artemisinin-treated group. This
      study revealed that artemisinin has the potential to be an alternative drug
      against trichinellosis.

PMID- 27894907
TI  - Seroprevalence and spatial distribution of Toxoplasma gondii infection in cats,
      dogs, pigs and equines of the Fernando de Noronha Island, Brazil.
AB  - Little is known about toxoplasmosis in animals of the Fernando de Noronha Island,
      Brazil. Therefore, we investigated the prevalence of Toxoplasma gondii infection
      in the total population of pet cats (n=348), dogs (n=320), pigs (n=27), equines
      (n=101), as well as a significant portion of the population of feral cats (n=247)
      of the Island by Indirect Fluorescent Antibody Test. Anti-T. gondii IgG
      antibodies were found in 71.26%, 54.74%, 48.75%, 51.85% and 22.7%, of the pet and
      feral cats, dogs, pigs and equines, respectively, demonstrating a high prevalence
      of T. gondii infection in the wild and domestic animals of the Island. The Kernel
      intensity estimator showed a correlation between areas with high prevalence of
      infection in cats and occurrence of infection in the other studied species. We
      suggest that the island's health authorities should develop initiatives to reduce
      the population of cats and alert the island's population about the risk of T.
      gondii infection.

PMID- 27894909
TI  - Characteristics of bystander cardiopulmonary resuscitation for paediatric out-of
      hospital cardiac arrests: A national observational study from 2012 to 2014.
AB  - OBJECTIVES: This study evaluated the associations between the provision of
      bystander cardiopulmonary resuscitation (BCPR) and both the relationship of
      bystanders with paediatric out-of-hospital cardiac arrest (OHCA) victims and the
      community educational level. METHODS: This observational study was conducted
      using the Korean national OHCA registry of paediatric OHCAs (<19years old)
      between 2012 and 2014. The main factor was the relationship between the bystander
      and the OHCA victim. The primary endpoint was the provision of BCPR. The
      association between BCPR provision and community educational level was also
      examined. Multivariable logistic regression and interaction analyses were
      performed to determine whether community educational level affected BCPR
      provision. RESULTS: Among the 1477 enrolled patients, 725 (49.1%) received BCPR.
      Family members provided BCPR in 458 (57.4%) cases. The adjusted odds ratios and
      corresponding 95% confidence intervals (AORs, 95% CIs) for the provision of BCPR
      by family members or first responders compared with strangers were 1.75 (1.31
      2.34) and 8.90 (5.00-15.84). The AORs for BCPR provision in communities with the
      middle and lowest educational levels compared with the highest were 0.70 (0.53
      0.92) and 1.11 (0.79-1.55). The interaction analysis showed that the AORs of
      family members or first responders providing BCPR compared with strangers were
      1.32 (0.79-2.19) and 5.90 (1.98-17.63), 1.98 (1.31-2.98) and 10.88 (4.20-28.16),
      and 1.87 (1.18-2.96) and 9.89 (3.88-25.21) in communities with the lowest, middle
      and highest educational levels, respectively. CONCLUSION: In paediatric OHCA
      cases, family members were more likely than strangers to perform BCPR except in
      communities with the lowest educational level.

PMID- 27894910
TI  - Cervical cancer screening in women vaccinated against human papillomavirus
      infection: Recommendations from a consensus conference.
AB  - In Italy, the cohorts of women who were offered Human papillomavirus (HPV)
      vaccination in 2007/08 will reach the age (25years) for cervical cancer (CC)
      screening from 2017. The simultaneous shift from cytology-based screening to HPV
      test-based screening gives the opportunity for unprecedented reorganisation of CC
      prevention. The ONS (National Screening Monitoring Centre) Directive and the
      GISCi (Italian Group for Cervical Screening) identified the consensus conference
      as the most suitable method for addressing this topic. A summary of consensus
      recommendations is reported here. The main objective was to define the best
      screening methods in girls vaccinated against HPV and the knowledge required for
      defining evidence-based screening strategies. A Jury made recommendations about
      questions and proposals formulated by a panel of experts representative of
      Italian scientific societies involved in CC prevention and based on systematic
      reviews of literature and evidence. The Jury considered changing the screening
      protocols for girls vaccinated in their twelfth year as appropriate. Tailored
      screening protocols based on vaccination status could be replaced by "one size
      fits all" protocols only when a herd immunity effect has been reached. Vaccinated
      women should start screening at age 30, instead of 25, with HPV test.
      Furthermore, there is a strong rationale for applying longer intervals for re
      screening HPV negative women than the currently recommended 5years, but research
      is needed to determine the optimal screening time points. For non-vaccinated
      women and for women vaccinated in their fifteenth year or later, the current
      protocol should be kept.

PMID- 27894911
TI  - Personal and provider level factors influence participation to cervical cancer
      screening: A retrospective register-based study of 1.3 million women in Norway.
AB  - High coverage is essential for an effective screening programme. Here we present
      screening barriers and facilitators among 1.3 million women aged 25-69years
      eligible for screening within the Norwegian Cervical Cancer Screening Program
      (NCCSP). We defined non-adherence as no screening test in 2008-2012. We divided
      adherent women into those screened spontaneously, and those who had a smear after
      receiving a reminder from the NCCSP. Explanatory variables were extracted from
      several nationwide registers, and modelled by modified Poisson regression. In
      total, 34% of women were non-adherent. 31% of native Norwegians were non
      adherent, compared to 50% of immigrants. Immigrant status was a strong predictor
      of non-adherence, but the vast majority of non-adherent women were still native
      Norwegians. Higher non-adherence rates were associated with having a male general
      practitioner (GP), a foreign GP, a young GP, and distance to the screening site.
      Being unmarried, having no children, having lower socioeconomic position and
      region of residence predicted non-adherence and, to a smaller extent, reminded
      adherence to screening. In contrast, previous experience with cervical
      abnormalities substantially increased adherence to screening. The population
      based screening programme promotes equity by recruiting women who are less likely
      to participate spontaneously. However, socioeconomic disparities were evident in
      a country with a nationwide programme and a policy of equal access to health
      care. Initiatives aimed at removing practical and financial barriers to equitable
      screening delivery and at reducing the effect of sociodemographic attributes on
      screening participation are needed.

PMID- 27894912
TI  - Hearing thresholds at high frequency in patients with cystic fibrosis: a
      systematic review.
AB  - INTRODUCTION: High-frequency audiometry may contribute to the early detection of
      hearing loss caused by ototoxic medications. Many ototoxic drugs are widely used
      in the treatment of patients with cystic fibrosis. Early detection of hearing
      loss should allow known harmful drugs to be identified before the damage affects
      speech frequencies. The damage caused by ototoxicity is irreversible, resulting
      in important social and psychological consequences. In children, hearing loss,
      even when restricted to high frequencies, can affect the development of language.
      OBJECTIVE: To investigate the efficacy and effectiveness of hearing monitoring
      through high-frequency audiometry in pediatric patients with cystic fibrosis.
      METHODS: Electronic databases PubMed, MedLine, Web of Science and LILACS were
      searched, from January to November 2015. The selected studies included those in
      which high-frequency audiometry was performed in patients with cystic fibrosis,
      undergoing treatment with ototoxic drugs and published in Portuguese, English and
      Spanish. The GRADE system was chosen for the evaluation of the methodological
      quality of the articles. RESULTS: During the search process carried out from
      January 2015 to November 2015, 512 publications were identified, of which 250
      were found in PubMed, 118 in MedLine, 142 in Web of Science and 2 in LILACS. Of
      these, nine articles were selected. CONCLUSION: The incidence of hearing loss was
      identified at high frequencies in cystic fibrosis patients without hearing
      complaints. It is assumed that high-frequency audiometry can be an early
      diagnostic method to be recommended for hearing investigation of patients at risk
      of ototoxicity.

PMID- 27894913
TI  - The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2alpha/chop
      pathway plays a vital role in bisphenol A-induced male reproductive toxicity.
AB  - Bisphenol A (2,2-bis(4-hydroxyphenyl)propane, BPA) is ubiquitous in the
      environment, wildlife, and humans. Evidence from past studies suggests that BPA
      is associated with decreased semen quality. However, the molecular basis for the
      adverse effect of BPA on male reproductive toxicity remains unclear. We evaluated
      the effect of BPA on mouse spermatocytes GC-2 cells and adult mice, and we
      explored the potential mechanism of its action. The results showed that BPA
      inhibited cell proliferation and increased the apoptosis rate. The testes from
      BPA-treated mice showed fewer spermatogenic cells and sperm in the seminiferous
      tubules. In addition, BPA caused reactive oxygen species (ROS) accumulation.
      Previous study has verified that mitochondrion was the organelle affected by the
      BPA-triggered ROS accumulation. We found that BPA induced damage to the
      endoplasmic reticulum (ER) in addition to mitochondria, and most ER stress
      related proteins were activated in cellular and animal models. Knocking down of
      the PERK/EIF2alpha/chop pathway, one of the ER stress pathways, partially
      recovered the BPA-induced cell apoptosis. In addition, an ROS scavenger
      attenuated the expression of the PERK/EIF2alpha/chop pathway-related proteins.
      Taken together, these data suggested that the ROS regulated PERK/EIF2alpha/chop
      pathway played a vital role in BPA-induced male reproductive toxicity.

PMID- 27894915
TI  - Postoperative temporal hollowing: Is there a surgical approach that prevents this
      complication? A systematic review and anatomic illustration.
AB  - BACKGROUND: Temporal hollowing is a common complication following surgical
      dissection in the temporal region. Our objectives were to: (1) review and clarify
      the temporal soft tissue relationships - supplemented by cadaveric dissection -
      to better understand surgical approach variations and elucidate potential
      etiologies of postoperative hollowing; (2) identify if there is any evidence to
      support a surgical approach that prevents hollowing through a systematic review.
      METHODS: Cadaveric dissection was performed on six hemi-heads. A systematic
      review of the literature was undertaken to identify surgical approaches with a
      decreased risk of postoperative hollowing. RESULTS: A total of 1212 articles were
      reviewed; 19 of these met final inclusion criteria. Level I and II evidence
      supports against the use of a dissection plane beneath the superficial layer of
      the deep temporal fascia or through the intermediate temporal fat pad. Level II
      evidence supports preservation of the temporalis muscle origin - no evidence is
      available to support other temporalis resuspension techniques. For intracranial
      exposure, refraining from temporal fat pad dissection (Level I Evidence) and use
      of decreased access approaches such as the minipterional craniotomy (Level I
      Evidence) appear to minimize temporal soft tissue atrophy. CONCLUSIONS: This
      study highlights the significance of preservation of the temporal soft tissue
      components to prevent hollowing. Preserving the temporalis origin and avoiding
      dissection between the leaflets of the deep temporal fascia or through the
      intermediate temporal fat pad appear to minimize this complication.

PMID- 27894914
TI  - The unexpected teratogenicity of RXR antagonist UVI3003 via activation of
      PPARgamma in Xenopus tropicalis.
AB  - The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show
      teratogenicity and, unexpectedly, induce similar malformations in Xenopus
      tropicalis embryos. In the present study, we exposed X. tropicalis embryos to
      UVI3003 in seven specific developmental windows and identified changes in gene
      expression. We further measured the ability of UVI3003 to activate Xenopus
      RXRalpha (xRXRalpha) and PPARgamma (xPPARgamma) in vitro and in vivo. We found
      that UVI3003 activated xPPARgamma either in Cos7 cells (in vitro) or Xenopus
      embryos (in vivo). UVI3003 did not significantly activate human or mouse
      PPARgamma in vitro; therefore, the activation of Xenopus PPARgamma by UVI3003 is
      novel. The ability of UVI3003 to activate xPPARgamma explains why UVI3003 and TPT
      yield similar phenotypes in Xenopus embryos. Our results indicate that activating
      PPARgamma leads to teratogenic effects in Xenopus embryos. More generally, we
      infer that chemicals known to specifically modulate mammalian nuclear hormone
      receptors cannot be assumed to have the same activity in non-mammalian species,
      such as Xenopus. Rather they must be tested for activity and specificity on
      receptors of the species in question to avoid making inappropriate conclusions.

PMID- 27894916
TI  - Reliability of extended dorsal intercostal artery perforator propeller flaps for
      reconstruction of large myelomeningocele defects.
AB  - Reconstruction of large myelomeningocele defects using extended (elongated beyond
      the lateral margin of the latissimus dorsi muscle) dorsal intercostal artery
      perforator (DICAP) propeller flaps is not recommended by previous studies.
      However, to provide tension-free and successful closure of a defect, the DICAP
      propeller flaps must sometimes be elongated beyond this margin. Our experience
      and results in this issue are discussed. In this article, reconstruction of 11
      consecutive cases, with large myelomeningocele defects in which standard DICAP
      propeller flaps were incapable to close the defect, was achieved using extended
      DICAP propeller flaps between June 2013 and November 2015. At least two reliable
      perforators of the neighboring intervertebral spaces are included to supply the
      flap. Intramuscular dissection of perforators is performed to free the
      perforators from the surrounding muscle and to gain pedicle length as much as
      possible to prevent twisting and vascular compromise. All the flaps survived
      completely except for one patient who had superficial skin necrosis on the most
      distal part of the flap and had severe accompanying systemic disorders and died
      on postoperative 14th day. In 7 of 11 patients, venous congestion was noted,
      which resolved spontaneously. No hematoma or seroma formation was observed during
      the postoperative follow-up period. Dissection of multiple DICAPs supplying flaps
      enable us to harvest larger DICAP flaps possibly by providing better arterial
      supply and venous drainage. We use microsurgical instruments and 4.3* loupe
      magnification for pedicle dissection in this newborn population. This study shows
      the reliability of extended DICAP propeller flaps when multiple perforators at
      sixth or more cranial adjacent intercostal spaces are included in DICAP propeller
      flaps.

PMID- 27894917
TI  - Incidence of breast implant rupture in a 12-year retrospective cohort: Evidence
      of quality discrepancy depending on the range.
AB  - BACKGROUND & OBJECTIVE: The majority of studies assessing the rupture rate of
      breast implants were performed by the breast implant manufacturing industry with
      questionable independence. After repetitive removals of ruptured implants from
      the same model, our team decided to assess the rupture rate and the estimated
      risk thereof for most of the silicone gel-filled implants we have used since they
      regained market approval in France in 2001. METHODS: Our study is a retrospective
      cohort of 809 patients operated in our University Hospital from 2001 to 2013 for
      cosmetic or reconstructive goals. We could track 1561 implants, 90% of them from
      the same manufacturer, Allergan (Irvine, CA, USA). For each of those, we gathered
      their exact reference, date of implantation, surgical approach, status, last
      follow-up visit or the eventual date, and cause of removal. RESULTS: Of 225
      explanted devices, only 27 were ruptured, all from the Allergan brand. Risks of
      removal for rupture were estimated: 0.5% at 1000 days, 6% at 2000 days, and 14%
      at 3000 days. Risks were significantly different between the models from this
      same manufacturer. One of the range of macro-textured round implants showed risks
      of removal for rupture of 33% at 3000 days compared to 6% for the anatomically
      shaped range. CONCLUSIONS: These results suggest a qualitative discrepancy among
      the different ranges of breast implants of a single manufacturer within the same
      timeframe of implantation. To determine the in vivo lifespan of the implants that
      we use more precisely and sooner, we suggest that each removed implant should be
      analyzed for wear and tear, independently from the industry.

PMID- 27894918
TI  - Laser speckle contrast imaging and Oxygen to See for assessing microcirculatory
      liver blood flow changes following different volumes of hepatectomy.
AB  - OBJECTIVE: Portal hyperperfusion after extended hepatectomy or small-for-size
      liver transplantation may induce organ dysfunction and failure. This study was
      designed to monitor and characterize the hepatic microcirculatory perfusion
      following different volumes of hepatectomy in rats by using laser speckle
      contrast image (LSCI) and Oxygen to See (O2C), a spectrometric device. METHODS:
      The microcirculatory liver blood flow of the rats that underwent 68%, 85% and 90%
      hepatectomy (68PH, 85PH and 90PH) was monitored with LSCI and O2C before and
      following the hepatectomy. The portal venous flow (PVF) and hepatic arterial flow
      (HAF) were measured with an ultrasonic flowmeter. Liver regeneration, liver
      injury, histologic evaluation and gene expression were also assessed at 12h, 24h,
      3d and 7d post hepatectomy. RESULTS: All the 68PH and 85PH rats survived, and 57%
      of the 90PH rats survived. After hepatectomy, both PVF and HAF decreased
      transiently, with the PVF of the 85PH and 90PH rats significantly lower than that
      of the 68PH rats. In contrast, the PVF and HAF per gram of liver weight were
      greatly increased after liver resection and were proportional to the volume of
      resected liver. Correspondingly, the microcirculatory liver blood flow of the
      68PH, 85PH and 90PH rats, as assessed by both LSCI and O2C, were increased after
      hepatectomy, and the 90PH group was significantly higher than the 68PH and 85PH
      groups. The hyperperfusion continued for approximately 3days and returned to
      baseline following the completion of liver regeneration. The liver venous oxygen
      saturation of the three groups decreased immediately after hepatectomy and
      returned to baseline from 24h after hepatectomy. The 90PH rats also showed
      delayed liver regeneration and the most severe liver injury, as reflected by
      increased serum ALT, AST and TBIL levels, hepatocellular vacuolization, and
      inflammatory and endothelial constriction gene expressions (TNF-alpha, IL-1beta,
      MIP-1alpha, ET-1 and TM-1). CONCLUSION: Hepatic microcirculation hyperperfusion
      resulting from major and extended liver resection could be assessed by LSCI and
      O2C methods. The 90PH in rats led to extraordinary sinusoidal hyperperfusion,
      severe endothelial injury and liver failure. Monitoring the changes of hepatic
      microcirculation perfusion following extended hepatectomy or small-for-size liver
      transplantation may help to analyze the extent of hyperperfusion.

PMID- 27894919
TI  - Resveratrol attenuates MPP+-induced mitochondrial dysfunction and cell apoptosis
      via AKT/GSK-3beta pathway in SN4741 cells.
AB  - Oxidative stress and mitochondrial dysfunction play crucial role in the
      dopaminergic neurons death, which is the pathological feature of Parkinson's
      disease (PD). Resveratrol (Res), a polyphenol derived from grapes and
      blueberries, has been reported to reduce oxidative stress injury and to restore
      mitochondrial function. In this study, we aimed to explore the underlying
      molecular mechanism of the beneficial effects of Res against MPP+- induced
      mitochondrial dysfunction and cell apoptosis in SN4741 cells. The data showed
      that Res significantly alleviated MPP+- induce cytotoxicity and restored MPP+-
      induced mitochondrial dysfunction in SN4741 cells. Moreover, Res rescued MPP+-
      induced a decline on the level of p-AKT, p-GSK-3betaand the ratio of Bcl-2/Bax,
      and an elevation on the expression of Bax and caspase-3, 9. However, inhibition
      GSK-3beta activity clearly abolished the protective effects of Res. Taken
      together, these results suggest that Res attenuates MPP+- induced mitochondrial
      dysfunction and cell apoptosis, and these protections may be achieved through
      AKT/GSK-3beta pathway. These also indicate that Res could be a promising
      therapeutic agent for PD.

PMID- 27894920
TI  - Effects of repeated dizocilpine treatment on glutamatergic activity in the
      prefrontal cortex in an animal model of schizophrenia: An in vivo proton magnetic
      resonance spectroscopy study at 9.4T.
AB  - Repeated exposure to dizocilpine (MK-801) can be used as a model of schizophrenia
      that incorporates disease progression. Proton magnetic resonance spectroscopy (1H
      MRS) has been widely used to investigate schizophrenia-related alterations in
      glutamate (Glu). The purpose of this study was to investigate metabolic
      alterations in the prefrontal cortex (PFC) in an animal model of schizophrenia by
      using in vivo 1H MRS. Because of the spectral overlap of Glu and glutamine (Gln),
      high-field 1H MRS with short echo time (TE) was used. A point-resolved
      spectroscopy sequence was used to measure the levels of Glu and Gln, and the
      brain metabolites in a volume of interest (22.5MUL) located in the PFC region of
      rats (n=13) before and after 6days of MK-801 (0.5mg/kg) treatment. Analysis of
      the spectra showed that the cross-contamination of Glu and Gln can be considered
      to comparably low. No metabolic parameters were altered (p>0.05). However,
      differences in Glu and N-acetylaspartate (NAA) levels between two times were
      significantly correlated (p<0.01). The results showed both decreased (in 6 of the
      13 rats) and increased (7 of the 13 rats) levels of Glu and NAA, which suggested
      that these opposite metabolic alterations reflect two stage of disease
      progression. The results suggest that high-field and short TE in vivo 1H MRS can
      quantify Glu and Gln with reliably low level of cross-contamination and that
      repeated exposure to MK-801 induces the progressive development of schizophrenia.

PMID- 27894921
TI  - Alterations of awake EEG in idiopathic REM sleep behavior disorder without
      cognitive impairment.
AB  - The aim of this study was to find electroencephalographic (EEG) changes in
      subjects with drug-naive idiopathic rapid eye movement sleep behavior disorder
      (iRBD) who had no cognitive impairment. A total of 57 iRBD patients confirmed by
      polysomnography (PSG) and 33 sex and age-matched healthy controls were included
      and their waking EEG was recorded from five cortical regions for 15min. Power
      spectral analyses by fast Fourier transforms were performed on EEG data. In PSG
      data, the iRBD patients showed sleep disturbances of short total sleep time,
      decreased sleep efficiency, increased sleep latency and frequent awakening
      compared to controls. After adjusting for sleep parameters, the absolute alpha
      power in frontal region in iRBD patients was higher than that in controls (1.2+/
      0.3 vs. 0.9+/-0.3, p=0.037). Dominant occipital frequency (DOF) was lower in iRBD
      patients than in controls after adjusting for the sleep covariates (9.2+/-0.3Hz
      vs. 9.5+/-0.4Hz, F=8, p=0.006). iRBD patients without cognitive impairment also
      showed EEG alteration in frontal and occipital cortex at wakefulness, which could
      be an early marker of cerebral dysfunction in iRBD patients.

PMID- 27894922
TI  - New preclinical model are required to discover neuroprotective compound in
      Parkinson's disease.

PMID- 27894923
TI  - Therapeutic implications of toll-like receptors in peripheral neuropathic pain.
AB  - Neuropathic pain is a state of chronic pain arising after peripheral or central
      nerve injury. These injuries can be mediated through the activation of various
      cells (astrocytes, microglia and Schwann cells), as well as the dissolution of
      distal axons. Recent studies have suggested that after nerve injury, Toll-like
      receptors (TLRs) involved in Wallerian degeneration and generation of neuropathic
      pain. Furthermore, these TLRs are responsible for the stimulation of astrocytes
      and microglia that can cause induction of the proinflammatory mediators and
      cytokines in the spinal cord, thereby leading to the generation and maintenance
      of neuropathic pain. Indeed considering the prevalence of neuropathic pain and
      suffering of the affected patients, insights into the diverse mechanism(s) of
      activation of TLR signaling cascades may open novel avenues for the management of
      this chronic condition. Moreover, existing therapies like antidepressants,
      anticonvulsants, opiates and other analgesic are not sufficiently effective in
      reducing the pain. In this review, we present substantial evidences highlighting
      the diverse roles of TLRs and their signaling pathways involved in the
      progression of neuropathic pain. Furthermore, an elaborate discussion on various
      existing treatment regimens and future targets involving TLRs has also been
      included.

PMID- 27894924
TI  - Antidepressant-like effects exerted by the intranasal administration of a
      glucagon-like peptide-2 derivative containing cell-penetrating peptides and a
      penetration-accelerating sequence in mice.
AB  - The intracerebroventicular (i.c.v.) administration of glucagon-like peptide-2
      (GLP-2) to rodents was shown to have antidepressant-like effects in imipramine
      resistant depression-model mice. In order to utilize GLP-2 as a clinical
      treatment tool for depression, we herein focused on the intranasal delivery that
      is non-invasive approach, because the i.c.v. administration is invasive and
      impractical. In the present study, we prepared a GLP-2 derivative containing cell
      penetrating peptides (CPPs) and a penetration accelerating sequence (PAS) (PAS
      CPPs-GLP-2) for the intranasal (i.n.) administration. PAS-CPPs-GLP-2 (i.n.)
      exhibited antidepressant-like effects in the forced-swim test (FST) and tail
      suspension test (TST) in naive mice as well as adrenocorticotropic hormone (ACTH)
      treated-mice. However, PAS-CPPs-GLP-2 (i.v.) and the GLP-2 derivative containing
      CPPs without a PAS (CPPs-GLP-2) (i.n.) did not affect the immobility time in the
      mouse FST. Moreover, fluorescein isothiocyanate (FITC)-labeled PAS-CPPs-GLP-2
      (i.n.), but not FITC-labeled CPPs-GLP-2 (i.n.) was distributed through the mouse
      brain after the FST session. These results suggest that PAS-CPPs-GLP-2 is
      effective for i.n. delivery to the brain, and may be useful in the clinical
      treatment of major depression.

PMID- 27894925
TI  - Dihydroceramide desaturase inhibitors induce autophagy via dihydroceramide
      dependent and independent mechanisms.
AB  - BACKGROUND: Autophagy consists on the delivery of cytoplasmic material and
      organelles to lysosomes for degradation. Research on autophagy is a growing field
      because deciphering the basic mechanisms of autophagy is key to understanding its
      role in health and disease, and to paving the way to discovering novel
      therapeutic strategies. Studies with chemotherapeutic drugs and pharmacological
      tools support a role for dihydroceramides as mediators of autophagy. However,
      their effect on the autophagy outcome (cell survival or death) is more
      controversial. METHODS: We have examined the capacity of structurally varied Des1
      inhibitors to stimulate autophagy (LC3-II analysis), to increase dihydroceramides
      (mass spectrometry) and to reduce cell viability (SRB) in T98G and U87MG
      glioblastoma cells under different experimental conditions. RESULTS: The
      compounds activity on autophagy induction took place concomitantly with
      accumulation of dihydroceramides, which occurred by both stimulation of ceramide
      synthesis de novo and reduction of Des1 activity. However, autophagy was also
      induced by the test compounds after preincubation with myriocin and in cells with
      a reduced capacity to produce dihydroceramides (U87DND). Autophagy inhibition
      with 3-methyladenine in the de novo dihydroceramide synthesis competent U87MG
      cells increased cytotoxicity, while genetic inhibition of autophagy in U87DND
      cells, poorly efficient at synthesizing dihydroceramides, augmented resistance to
      the test compounds. CONCLUSION: Dihydroceramide desaturase 1 inhibitors activate
      autophagy via both dihydroceramide-dependent and independent pathways and the
      balance between the two pathways influences the final cell fate. GENERAL
      SIGNIFICANCE: The cells capacity to biosynthesize dihydroceramides must be taken
      into account in proautophagic Des1 inhibitors-including therapies.

PMID- 27894926
TI  - Introduction: Towards a better understanding of the science of RLS/WED.

PMID- 27894928
TI  - Per-oral video cholangiopancreatoscopy with narrow-band imaging for the
      evaluation of indeterminate pancreaticobiliary disease.
AB  - BACKGROUND AND AIMS: Cholangiopancreatoscopy for evaluating pancreaticobiliary
      pathology is currently limited by suboptimal optics. The aim of this study was to
      characterize the operating characteristics of per-oral video
      cholangiopancreatoscopy with narrow-band imaging (POVCP) findings in
      indeterminate pancreaticobiliary disease and to describe their association with
      neoplasia. METHODS: Data from consecutive patients undergoing POVCP for the
      evaluation of indeterminate pancreaticobiliary disease at a single tertiary care
      center were analyzed. Two experienced investigators had previously agreed on
      POVCP findings and terminology that were documented in endoscopy reports.
      Endoscopic procedural data from POVCPs performed between January 2006 and April
      2015 and clinical data were abstracted from the endoscopic database and
      electronic medical records. Study endpoints included tissue-proven neoplasia or
      benign disease with >=1 year of follow-up. RESULTS: A total of 109 patients were
      identified; 13 were excluded because of the presence of stone disease, known
      pancreaticobiliary malignancy, or presumed benign disease with <=1 year of follow
      up. Most patients (85%) underwent POVCP for biliary disease and 15% underwent
      POVCP for a pancreatic cause. Tortuous and dilated vessels (P < .001),
      infiltrative stricture (P < .001), polypoid mass (P = .003), and the presence of
      fish-egg lesions (P = .04) were found to be significantly associated with
      neoplasia. The overall POVCP impression had a high sensitivity (85%) and negative
      predictive value (89%) in assessing for the presence of neoplasia. CONCLUSIONS:
      Per-oral video cholangiopancreatoscopy is effective in the evaluation of
      indeterminate pancreaticobiliary disease. Tortuous and dilated vessels,
      infiltrative stricture, polypoid mass, and the presence of fish-egg lesions are
      significantly associated with neoplasia.

PMID- 27894929
TI  - Ultrathin disposable gastroscope for screening and surveillance of
      gastroesophageal varices in patients with liver cirrhosis: a prospective
      comparative study.
AB  - BACKGROUND AND AIMS: This study aims to evaluate the role of unsedated, ultrathin
      disposable gastroscopy (TDG) against conventional gastroscopy (CG) in the
      screening and surveillance of gastroesophageal varices (GEVs) in patients with
      liver cirrhosis. METHOD: Forty-eight patients (56.4 +/- 1.3 years; 38 male, 10
      female) with liver cirrhosis referred for screening (n = 12) or surveillance (n =
      36) of GEVs were prospectively enrolled. Unsedated gastroscopy was initially
      performed with TDG, followed by CG with conscious sedation. The 2 gastroscopies
      were performed by different endoscopists blinded to the results of the previous
      examination. Video recordings of both gastroscopies were validated by an
      independent investigator in a random, blinded fashion. Endpoints were accuracy
      and interobserver agreement of detecting GEVs, safety, and potential cost saving.
      RESULTS: CG identified GEVs in 26 (54%) patients, 10 of whom (21%) had high-risk
      esophageal varices (HREV). Compared with CG, TDG had an accuracy of 92% for the
      detection of all GEVs, which increased to 100% for high-risk GEVs. The
      interobserver agreement for detecting all GEVs on TDG was 88% (kappa = 0.74).
      This increased to 94% (kappa = 0.82) for high-risk GEVs. There were no serious
      adverse events. CONCLUSIONS: Unsedated TDG is safe and has high diagnostic
      accuracy and interobserver reliability for the detection of GEVs. The use of
      clinic-based TDG would allow immediate determination of a follow-up plan, making
      it attractive for variceal screening and surveillance programs. (Clinical trial
      (ANZCTR) registration number: ACTRN12616001103459.).

PMID- 27894931
TI  - The unique status of first-in-human studies: strengthening the social value
      requirement.
AB  - For clinical research to be ethical, risks need to be balanced by anticipated
      benefits. This is challenging for first-in-human (FIH) studies as participants
      are not expected to benefit directly, and risks are potentially high. We argue
      that this differentiates FIH studies from other clinical trials to the extent
      that they should be given unique status in international research ethics
      guidelines. As there is a general positive attitude regarding the benefits of
      science, it is important to establish a more systematic method to assess
      anticipated social value to safeguard participants not only from enrolling in
      risky, but also in futile trials. Here, we provide some of necessary steps needed
      to assess the anticipated social value of the intervention.

PMID- 27894930
TI  - Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol
      consumption; study of neurobiological consequences.
AB  - Alcohol use disorder and depression are highly comorbid, and both conditions
      exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary
      alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats -
      employed as an animal model of depression. Male and female rats were
      investigated, and changes in several molecular markers were analysed in frontal
      cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like
      responses in the forced swimming test - increased immobility time - in male and
      female animals, without affecting anhedonia (sucrose preference test) nor motor
      activity (holeboard); body weight gain and food intake were diminished only among
      CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice
      paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited
      a higher preference for alcohol compared to male animals. In particular, alcohol
      consumption was significantly higher among CMS females compared to CMS male
      animals. Remarkably, similar changes in both male and female animals exposed to
      CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP
      and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels
      (increase). However, contrasting effects in males and females were reported in
      relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression
      (a decrease among male animals but an increase in females); while the opposite
      pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R
      expression was only observed in the HF of CMS-females. The present study suggests
      that male and female animals might be differentially affected by CMS regarding
      later voluntary alcohol consumption. In this initial approach, cortical SYN, and
      NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential
      candidates to explain such sex differences in behaviour. However, the depression
      alcoholism relationship still deserves further investigation.

PMID- 27894932
TI  - Microbial stress: From molecules to systems (Sitges, November 2015).
AB  - The meeting "Microbial Stress: from Molecules to Systems" - the third in this
      series - was held in Sitges (Spain) in November 2015. The meeting offered the
      opportunity for international scientists to share their viewpoints and recent
      outcomes concerning microbial stress responses. Particular attention was given to
      the characterisation of mechanisms triggered by stress, from detailed molecular
      biology through whole organism systems biology up to the level of populations. A
      deeper understanding of microbial responses to stress is indeed attainable only
      considering the phenomenon as a whole. Exhaustive knowledge of the various stress
      response systems, and of their interconnections, is important for different
      applications, from the prevention and counteraction of bacterial infectious
      diseases to the engineering of robust cell factories. The presentations covered
      all of these aspects, enabling an active interaction among participants. It also
      stimulated discussions and cross-fertilisation among disciplines, which was one
      of the aims of the meeting. Moreover, since many stress response mechanisms are
      broadly conserved, data obtained at the microbial scale may facilitate the
      comprehension of complex phenomena, such as aging, evolution of neurological
      diseases and cancer.

PMID- 27894933
TI  - Parasitism, personality and cognition in fish.
AB  - It is well established that parasites can have profound effects on the behaviour
      of host organisms, and that individual differences in behaviour can influence
      susceptibility to parasite infections. Recently, two major themes of research
      have developed. First, there has been a growing interest in the proximate,
      mechanistic processes underpinning parasite-associated behaviour change, and the
      interactive roles of the neuro-, immune, and other physiological systems in
      determining relationships between behaviour and infection susceptibility.
      Secondly, as the study of behaviour has shifted away from one-off measurements of
      single behaviours and towards a behavioural syndromes/personality framework,
      research is starting to focus on the consequences of parasite infection for
      temporal and contextual consistency of behaviour, and on the implications of
      different personality types for infection susceptibility. In addition, there is
      increasing interest in the potential for relationships between cognition and
      personality to also have implications for host-parasite interactions. As models
      well-suited to both the laboratory study of behaviour and experimental
      parasitology, teleost fish have been used as hosts in many of these studies. In
      this review we provide a broad overview of the range of mechanisms that
      potentially generate links between fish behaviour, personality, and parasitism,
      and illustrate these using examples drawn from the recent literature. In
      addition, we examine the potential interactions between cognition, personality
      and parasitism, and identify questions that may be usefully investigated with
      fish models.

PMID- 27894934
TI  - MiR-142 Is Required for Staphylococcus aureus Clearance at Skin Wound Sites via
      Small GTPase-Mediated Regulation of the Neutrophil Actin Cytoskeleton.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein translation by
      binding to complementary target mRNAs. We previously identified two mature
      members of the miR-142 family, miR-142-5p and miR-142-3p, as inflammation-related
      miRNAs with potential roles in wound healing. Here, we demonstrated that these
      two miRNAs are prominently expressed in wound-infiltrated neutrophils and
      macrophages and play central roles in wound healing. We generated miR-142-/- mice
      using the exchangeable gene-trap method and showed that healing of Staphylococcus
      aureus-infected skin wounds was significantly delayed in miR-142-/- mice compared
      with that in wild-type mice. MiR-142-/- mice exhibited abnormal abscess formation
      at S. aureus-infected skin wound sites and were also more susceptible to
      horizontal transmission of wound infections. MiR-142-/- neutrophils showed
      altered phagocytosis as a consequence of chemotactic behavior, including enhanced
      F-actin assembly, disturbed cell polarity, and increased cell motility. We showed
      that these changes were linked to cytoskeletal regulation, and that expression of
      the small GTPases was markedly increased in miR-142-/- neutrophils. Collectively,
      our data demonstrate that the miR-142 family is indispensable for protection
      against S. aureus infection and its clearance at wound sites. MiR-142-3p and miR
      142-5p play nonredundant roles in actin cytoskeleton regulation by controlling
      small GTPase translation in neutrophils at wound sites.

PMID- 27894935
TI  - Stage-specific differences in secretory profile of mesenchymal stromal cells
      (MSCs) subjected to early- vs late-stage OA synovial fluid.
AB  - OBJECTIVE: Although, mesenchymal stromal cells (MSCs) are being clinically
      investigated for their use in osteoarthritis (OA), it is unclear whether their
      postulated therapeutic properties are equally effective in the early- and late
      stages of OA. In this study we investigated MSC cytokine secretion post-exposure
      to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to
      justify a potential patient stratification strategy to maximize MSC-mediated
      treatment effects. METHOD: Subjects were recruited and categorized into early-
      [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12)
      knee OA groups. SF samples were obtained, and their proteome was tested using
      multiplex assays, after 3-days culture, with and without MSCs. SFs cultured
      without MSCs were used as a baseline to identify MSC-secreted factors into SFs
      cultured with MSCs. Linear mixed-effect models and non-parametric tests were used
      to identify alterations in the MSC secretome during exposure to OA SF (3-days).
      MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium
      were used to compare SF results with culture medium. RESULTS: Following exposure
      to OA SF, the MSC secretome contained proteins that are involved in tissue
      repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process.
      However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6
      (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC
      secretome in response to early- vs late-stage OA SF. CONCLUSION: Early- vs late
      stage OA SF samples elicit a differential MSC secretome response, arguing for
      stratification of OA patients to maximize MSC-mediated therapeutic effects.

PMID- 27894937
TI  - Cell cycle arrest in the jewel wasp Nasonia vitripennis in larval diapause.
AB  - Insects enter diapause to synchronise their life cycle with biotic and abiotic
      environmental conditions favourable for their development, reproduction, and
      survival. One of the most noticeable characteristics of diapause is the blockage
      of ontogeny. Although this blockage should occur with the cessation of cellular
      proliferation, i.e. cell cycle arrest, it was confirmed only in a few insect
      species and information on the molecular pathways involved in cell cycle arrest
      is limited. In the present study, we investigated developmental and cell cycle
      arrest in diapause larvae of the jewel wasp Nasonia vitripennis. Developmental
      and cell cycle arrest occur in the early fourth instar larval stage of N.
      vitripennis under short days. By entering diapause, the S fraction of the cell
      cycle disappears and approximately 80% and 20% of cells arrest their cell cycle
      in the G0/G1 and G2 phases, respectively. We further investigated expression of
      cell cycle regulatory genes and some housekeeping genes to dissect molecular
      mechanisms underlying the cell cycle arrest.

PMID- 27894936
TI  - Identification and expression analyses of vitellogenin in Bactericera cockerelli
      (Sulc).
AB  - The potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), is a
      phloem-feeding insect with preference for Solanaceae. This insect species is
      vector of the pathogenic bacteria 'Candidatus Liberibacter solanacearum' the
      causative agent of zebra chip, an important disease of commercial potatoes in
      several countries worldwide. The recent classification of psyllids among the most
      dangerous vectors has promoted their study, but still many biological processes
      such as reproduction and vitellogenesis need to be investigated. As a first step
      towards the elucidation of vitellogenesis in B. cockerelli, one candidate
      vitellogenin transcript (6622 bases long) was identified and the expression of
      the transcript and the protein were analyzed in virgin and mated females between
      1 and 7days old. In virgin females, Vg expression increased up to 5days old;
      while mating significantly up-regulated Vg expression in 5- and 7-day-old
      females. To determine the role of juvenile hormone in B. cockerelli Vg
      expression, topical applications of juvenile hormone III were performed on virgin
      females, resulting in an up-regulation of Vg expression and an increase in the
      number of mature oocytes present in female reproductive organs. Overall, this
      study represents the first step to understand vitellogenesis of B. cockerelli and
      it highlights the role of JH III in the hormonal regulation of Vg expression and
      oocyte development.

PMID- 27894938
TI  - Integrating Postoperative Feedback Into Workflow: Perceived Practices and
      Barriers.
AB  - OBJECTIVE: Previous studies have found that both resident and staff surgeons
      highly value postoperative feedback; and that such feedback has high educational
      value. However, little is known about how to consistently deliver this feedback.
      Our aim was to understand how often surgical residents should receive feedback
      and what barriers are preventing this from occurring. DESIGN: Surveys were
      distributed to resident and attending surgeons. Questions focused on the current
      frequency of postoperative feedback, desired frequency and methods of feedback,
      and perceived barriers. Quantitative data were analyzed with descriptive
      statistics, and text responses were examined using coding. SETTING: University
      based general surgery department at a Midwestern institution. PARTICIPANTS:
      General surgery residents (n = 23) and attending surgeons (n = 22) participated
      in this study. RESULTS: Residents reported receiving and staff reported giving
      feedback for procedure-specific performance after 25% versus 34% of cases,
      general technical feedback after 36% versus 32%, and nontechnical performance
      after 17% versus 18%. Both perceived procedure-specific and general technical
      feedback should be given more than 80% of the time, and nontechnical feedback
      should happen for nearly 60% of cases. Verbal feedback immediately after the
      operation was rated as best practice. Both parties identified time, conflicting
      responsibilities, lack of privacy, and discomfort with giving and receiving
      meaningful feedback as barriers. CONCLUSIONS: Both resident and staff surgeons
      agree that postoperative feedback is given far less often than it should. Future
      work should study intraoperative and postoperative feedback to validate resident
      and attending surgeons' perceptions such that interventions to improve and
      facilitate this process can be developed.

PMID- 27894940
TI  - Changes in the mRNA expression of structural proteins, hormone synthesis and
      secretion from bovine placentome sections after DDT and DDE treatment.
AB  - Disorders in the barrier function and secretory activity of the placenta can be
      caused by xenobiotics (XB) present in the environment and their accumulation in
      tissues of living organisms. Thus, the aim of this study was to investigate the
      effect of 1,1,1-trichloro-2,2,-bis-4-chlorophenyl-ethane (DDT) and its metabolite
      1,1-dichloro-2,2-bis-4-chlorophenyl-ethene (DDE) (for 24 or 48h) at doses of 1,
      10 or 100ng/ml on the function of cow placentome sections in the second trimester
      of pregnancy. DDT and DDE affected neither (P>0.05) the viability nor hypoxia
      inducible factor 1 (HIF1alpha) mRNA expression of the sections. XB decreased
      (P<0.05) connexin (Cx) 26, 32, 43 and placenta-specific 1 (PLAC-1) mRNA
      expression but did not affect (P>0.05) keratin 8 (KRT8) mRNA expression. DDT and
      DDE also reduced (P<0.05) prostaglandin F2alpha (PGF2alpha) synthase (PGFS) mRNA
      expression, while DDT increased (P<0.05) prostaglandin E2 (PGE2) synthase (PGES)
      mRNA expression. Neither cyclooxygenase 2 (COX-2) mRNA expression nor PGF2alpha
      and PGE2 secretion were affected. Both DDT and DDE increased (P<0.05) neurophysin
      I/oxytocin (NP1/OT) mRNA expression and oxytocin (OT), oestradiol (E2) and
      progesterone (P4) secretion while DDT stimulated only 3beta-hydroxysteroid
      dehydrogenase (3betaHSD) and cholesterol side-chain cleavage enzyme (CYP11A1)
      mRNA expression (P<0.05). In summary, DDT and DDE impaired the barrier function
      and secretory activity of the placenta. Thus, these compounds can disrupt
      trophoblast invasion, myometrium contractility and gas/nutrient exchange
      throughout pregnancy in cows.

PMID- 27894939
TI  - Intranasal Cerebrolysin Attenuates Learning and Memory Impairments in D-galactose
      Induced Senescence in Mice.
AB  - Neurotrophic factors are currently being considered as pro-cognitive therapeutic
      approaches for management of cognitive deficits. This study aims to evaluate the
      effects of intranasal (i.n.) or intraperitoneal (i.p.) administration of
      Cerebrolysin (CBL) (as a mixture of neurotrophic factors) on the d-galactose
      induced oxidative stress, apoptosis and memory as well as learning impairment in
      mice. For this purpose, CBL (1, 2.5, 5 ml/kg/i.p.) or (1 ml/kg/i.n.), were
      administrated daily in d-galactose-received (100 mg/kg/subcutaneous (s.c.)) mice
      model of aging for eight weeks. Spatial and recognition memories were assessed by
      the Morris water maze and novel object recognition tasks. Brain and blood of
      animals were analysed for oxidative stress biomarkers including malondialdehyde,
      total antioxidant capacity, glutathione peroxidase and superoxide dismutase.
      Apoptosis rate in the hippocampus was evaluated by TUNEL staining of brain
      tissue. 5 ml/kg/i.p. dose of CBL increased the locomotor activity but, 1
      ml/kg/i.p. dose didn't show detectable behavioural or molecular effects on aged
      mice. Treatment with 2.5 ml/kg/i.p. and 1 ml/kg/i.n. doses attenuated d-galactose
      impaired spatial and recognition memories. Results showed an obvious increase in
      the antioxidant biomarkers and decrease in the malondialdehyde levels both in the
      blood and brain of aged mice in 2.5 ml/kg/i.p. dose, and only in the brain in 1
      ml/kg/i.n. dose of CBL. Anti-apoptotic effects also were seen in the same
      dose/rout of CBL administration in aged animals. This study proves the usefulness
      of i.n. CBL administration as a non-invasive and efficient method of drug
      delivery to the brain to improve aging-induced oxidative stress, apoptosis and
      learning as well as memory impairment.

PMID- 27894941
TI  - One year of abaloparatide, a selective peptide activator of the PTH1 receptor,
      increased bone mass and strength in ovariectomized rats.
AB  - Abaloparatide is a novel 34 amino acid peptide selected to be a potent and
      selective activator of the parathyroid hormone receptor 1 (PTHR1) signaling
      pathway. The effects of 12months of abaloparatide treatment on bone mass, bone
      strength and bone quality was assessed in osteopenic ovariectomized (OVX) rats.
      SD rats were subjected to OVX or sham surgery at 6months of age and left
      untreated for 3months to allow OVX-induced bone loss. Eighteen OVX rats were
      sacrificed after this bone depletion period, and the remaining OVX rats received
      daily s.c. injections of vehicle (n=18) or abaloparatide at 1, 5 or 25MUg/kg/d
      (n=18/dose level) for 12months. Sham controls (n=18) received vehicle daily. Bone
      changes were assessed by DXA and pQCT after 0, 3, 6 or 12months of treatment, and
      destructive biomechanical testing was conducted at month 12 to assess bone
      strength and bone quality. Abaloparatide dose-dependently increased bone mass at
      the lumbar spine and at the proximal and diaphyseal regions of the tibia and
      femur. pQCT revealed that increased cortical bone volume at the tibia was a
      result of periosteal expansion and endocortical bone apposition. Abaloparatide
      dose-dependently increased structural strength of L4-L5 vertebral bodies, the
      femur diaphysis, and the femur neck. Increments in peak load for lumbar spine and
      the femur diaphysis of abaloparatide-treated rats persisted even after adjusting
      for treatment-related increments in BMC, and estimated material properties were
      maintained or increased at the femur diaphysis with abaloparatide. The
      abaloparatide groups also exhibited significant and positive correlations between
      bone mass and bone strength at these sites. These data indicate that gains in
      cortical and trabecular bone mass with abaloparatide are accompanied by and
      correlated with improvements in bone strength, resulting in maintenance or
      improvement in bone quality. Thus, this study demonstrated that long-term daily
      administration of abaloparatide to osteopenic OVX rats led to dose-dependent
      improvements in bone mass, geometry and strength.

PMID- 27894942
TI  - Masson Hemangioma-An Unusual Cause of Thoracic Compressive Myelopathy.
AB  - BACKGROUND: Masson hemangioma is a rare pathologic entity characterized by
      intravascular papillary endothelial hyperplasia. Although benign, this hemangioma
      grows to form an expansile compressing mass. This lesion is mostly seen in skin
      and subcutaneous tissue. Occurrence in the central nervous system is rare. Still
      rarer is a spinal location with only 5 case reports published to date in the
      literature. CASE DESCRIPTION: A 32-year-old man presented with paraplegia
      secondary to extradural compression at the T4-5 level. Histopathologic features
      were consistent with intravascular papillary endothelial hyperplasia, also known
      as Masson hemangioma. Differential diagnosis, management, and review of
      literature are discussed in this report. CONCLUSIONS: This rare pathology should
      be in the differential diagnosis when spinal cord compressive myelopathy is
      encountered.

PMID- 27894927
TI  - The dynamics of GABA signaling: Revelations from the circadian pacemaker in the
      suprachiasmatic nucleus.
AB  - Virtually every neuron within the suprachiasmatic nucleus (SCN) communicates via
      GABAergic signaling. The extracellular levels of GABA within the SCN are
      determined by a complex interaction of synthesis and transport, as well as
      synaptic and non-synaptic release. The response to GABA is mediated by GABAA
      receptors that respond to both phasic and tonic GABA release and that can produce
      excitatory as well as inhibitory cellular responses. GABA also influences
      circadian control through the exclusively inhibitory effects of GABAB receptors.
      Both GABA and neuropeptide signaling occur within the SCN, although the
      functional consequences of the interactions of these signals are not well
      understood. This review considers the role of GABA in the circadian pacemaker, in
      the mechanisms responsible for the generation of circadian rhythms, in the
      ability of non-photic stimuli to reset the phase of the pacemaker, and in the
      ability of the day-night cycle to entrain the pacemaker.

PMID- 27894943
TI  - Acquired Chiari Malformation and Syringomyelia Secondary to Space-Occupying
      Lesions: A Systematic Review.
AB  - BACKGROUND: Acquired Chiari malformations (ACM) and associated syringomyelia
      secondary to space-occupying lesions can cause neurologic deficits independent of
      or in combination with the offending mass. Although type I Chiari malformations
      are traditionally treated with posterior fossa decompression, optimal surgical
      management of ACM and associated syringomyelia remains unclear. The purpose of
      this study is to review the current literature surrounding the management of ACM.
      METHODS: A systematic review was performed in accordance with the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using the
      relevant keywords, articles were identified through multiple databases from
      inception to April 2016. Our primary outcome was postoperative resolution of
      tonsillar herniation, syringomyelia, and clinical symptoms and signs. RESULTS:
      Thirty studies (27 case reports and 3 case series), encompassing 44 patients,
      were included in the review. Meningiomas (36%) and arachnoid cysts (32%) were the
      lesions most commonly associated with ACM. Offending lesions were usually large
      (85%) and almost all were found in the posterior fossa (89%). Syringomyelia was
      present in 82% of cases. Overall, all but 1 patient had improvement or resolution
      of their syringomyelia after surgery and none required a syrinx shunt. Rates of
      tonsillar ascent, syrinx resolution, and neurologic recovery were similar in
      patients who underwent lesion removal alone versus those who underwent posterior
      fossa decompression and lesion removal. CONCLUSIONS: Space-occupying lesions in
      the posterior fossa are a rare cause of ACM and syringomyelia. Surgical
      management of the underlying lesion improves ACM and associated syringomyelia
      without the need for syrinx shunting.

PMID- 27894944
TI  - SUrface-PRojected FLuid-Attenuation-Inversion-Recovery Analysis: A Novel Tool for
      Advanced Imaging of Epilepsy.
AB  - OBJECTIVE: The objective of this pilot retrospective study is to describe the
      SUrface-PRojected FLuid-Attenuation-Inversion-Recovery (SUPR-FLAIR) analysis, a
      novel method mainly aimed at revealing cortical areas with subtle signal
      hyperintensity. METHODS: Images from 101 healthy controls and 10 patients
      suffering from drug-resistant partial epilepsy were retrospectively
      postprocessed. The brain surface was reconstructed from a 3-dimensional (3D) T1
      weighted fast field echo (T1W-FFE) magnetic resonance imaging (MRI) scan. A turbo
      spin echo fluid attenuated inversion recovery axial scan was registered to the 3D
      T1W-FFE scan, and its intensity values were normalized. The cortical intensity
      signal was projected onto the brain surface, and surface-based analysis was
      performed, comparing each patient against the 101 controls. The localizations of
      the first positive lower P value cluster (PLPC) peak and the resection zone (RZ)
      were compared. We studied 5 patients with focal cortical dysplasia (3 of them
      with negative MRI) and 5 with hippocampal sclerosis. RESULTS: SUPR-FLAIR analysis
      localized the first PLPC peak in the RZ in all cases. Because all patients have
      been seizure free since surgery, it can be assumed that the epileptogenic zone
      (EZ) was included in the RZ. Therefore, SUPR-FLAIR analysis correctly aligned
      with the EZ, with 100% sensitivity. CONCLUSIONS: SUPR-FLAIR analysis is a
      noninvasive technique that could be helpful for the definition of the EZ,
      especially when MRI is negative. Its use could reduce the indications for
      invasive electroencephalography or could provide essential data to refine the
      strategy of intracerebral electrode implantation in the most challenging cases.

PMID- 27894945
TI  - Successful Treatment of Refractory Status Epilepticus Using Anterior Thalamic
      Nuclei Deep Brain Stimulation.
AB  - BACKGROUND: Refractory status epilepticus (RSE) is considered a medical emergency
      in neurology and is related to high mortality. We report a successfully treated
      case of RSE using deep brain stimulation (DBS) at the anterior thalamic nuclei
      (ATN) in a 17-year-old woman. RESULTS: This patient developed RSE as a result of
      progressive seizure activity. RSE with generalized tonic-clonic seizures was
      noted 2 weeks before admission. Video electroencephalography monitoring showed
      continuous 3-Hz generalized spike-and-wave complexes with higher amplitude over
      bilateral frontal. Four weeks after RSE onset, bilateral DBS of the ATN was
      started. This treatment was immediately followed by the disappearance of tonic
      clonic seizures and spike-and-wave complexes, suggesting resolution of the RSE.
      Significant clinical improvement was noted 1 week after DBS implantation.
      CONCLUSIONS: DBS at the ATN significantly improved both the
      electroencephalography and clinical presentation in the patient with RSE. DBS at
      the ATN should be considered as a possible treatment choice once a patient
      develops RSE.

PMID- 27894947
TI  - Strategies to identify natural antisense transcripts.
AB  - Natural antisense transcripts, originally considered as transcriptional noises
      arising from so-called "junk DNA", are recently recognized as important
      modulators for gene regulation. They are prevalent in nearly all realms of life
      and have been found to modulate gene expression positively or negatively. By
      affecting almost all stages of gene expression range from pre-transcriptional,
      transcriptional and post-transcriptional to translation, NATs are fundamentally
      involved in various biological processes. However, compared to increasing huge
      data from transcriptional analysis especially high-throughput sequencing
      technologies (such as RNA-seq), limited functional NATs (around 70) are so far
      reported, which hinder our advanced comprehensive understanding for this field.
      Hence, efficient strategies for identifying NATs are urgently desired. In this
      review, we discussed the current strategies for identifying NATs, with a focus on
      the advantages, disadvantages, and applications of methods isolating functional
      NATs. Moreover, publicly available databases for NATs were also discussed.

PMID- 27894946
TI  - The emerging role of long non-coding RNA in gallbladder cancer pathogenesis.
AB  - Gallbladder cancer (GBC) is the most common and aggressive form of biliary tract
      carcinoma with an alarmingly low 5-year survival rate. Despite its high mortality
      rate, the underlying mechanisms of GBC pathogenesis are not completely
      understood. Recently, from a growing volume of literature, long non-coding RNAs
      (lncRNAs) have emerged as key regulators of gene expression and appear to play
      vital roles in many human cancers. To date, a number of lncRNAs have been
      implicated in GBC, but their potential roles in GBC have not been systematically
      examined. Thus, in this review, we critically discuss the emerging roles of
      lncRNAs in GBC, and the pathways involved. Specifically, we note that some
      lncRNAs show greater expression in T1 and T2 tumor stages compared to T3 and T4
      tumor stages and that their dysregulation leads to alterations in cell cycle
      progression and can cause an increase in GBC cell proliferation or apoptosis. In
      addition, some lncRNAs control the epithelial-mesenchymal transition process,
      while others take part in the regulation of ERK/MAPK and Ras cancer-associated
      signaling pathways. We also present their potential utility in diagnosis,
      prognosis, and/or treatment of GBC. The overall goal of this review is to
      stimulate interest in the role of lncRNAs in GBC, which may open new avenues in
      the determination of GBC pathogenesis and may lead to the development of new
      preventive and therapeutic strategies for GBC.

PMID- 27894948
TI  - Don't be rejected, how can we help authors, reviewers and editors?: Report of a
      Symposium for Editors Publishers and Others with an Interest in Scientific
      Publication, Held in Boston on Wednesday, 11 March 2015, during the Annual
      Meeting of the International Association for Dental Research.
AB  - This satellite symposium was the fifth in a series for editors, publishers,
      reviewers and all those with an interest in scientific publishing. It was held on
      Wednesday, 11 March 2015 at the IADR meeting in Boston, Massachusetts. The
      symposium attracted more than 210 attendees. The symposium placed an emphasis on
      strategies to ensure that papers are accepted by peer reviewed journals. The
      speaker, representing the Journal of Dental Research gave a history of peer
      review and explained how to access material to advise new authors. The speaker
      from India outlined the problems that occur when there is no culture for dental
      research and it is given a low priority in dental education. He outlined
      remedies. The speaker from SAGE publications described the help that publishers
      and editors can provide authors. The final speaker suggested that in developing
      countries it was essential to create alliances with dental researchers in
      developed countries and that local conferences to which external speakers were
      invited, stimulated research both in terms of quantity and quality. A wide
      ranging discussion then took place.

PMID- 27894950
TI  - Untying the Gordian knot of pericardial diseases: A pragmatic approach.
AB  - Pericardial disorders constitute a relatively common cause of heart disease.
      Although acute pericarditis, especially the idiopathic forms that are the most
      prevalent, is considered a benign disease overall, its short- and long-term
      complications, namely, recurrent pericarditis, cardiac tamponade and constrictive
      pericarditis, constitute a matter of concern in the medical community. In recent
      years, several clinical trials contributed to redefining our traditional approach
      to pericardial diseases. In this review, we provide the most recent evidence
      concerning diagnosis, treatment modalities and short- and long-term prognosis of
      the most common pericardial disorders.

PMID- 27894949
TI  - Intravascular hemodynamics and coronary artery disease: New insights and clinical
      implications.
AB  - Intracoronary hemodynamics play a pivotal role in the initiation and progression
      of the atherosclerotic process. Low pro-inflammatory endothelial shear stress
      impacts vascular physiology and leads to the occurrence of coronary artery
      disease and its implications.

PMID- 27894951
TI  - A pilot study of CXCL8 levels in crystal proven gout patients during allopurinol
      treatment and their association with cardiovascular disease.
AB  - OBJECTIVES: Gout is associated with cardiovascular diseases, and systemic
      inflammation has a role in this. CXCL8 (interleukin-8) levels were increased in
      synovial fluid of gout patients, and in serum in gout patients irrespective of
      their disease activity. We hypothesized that the well-known cardiovascular
      protective effects of allopurinol could be related to effects of this drug on
      CXCL8 levels. METHODS: Patients with a crystal proven gout diagnosis, who newly
      started allopurinol treatment, were included in this prospective cohort study.
      After evaluation at baseline for cardiovascular diseases, tophi, uric acid, CRP
      and CXCL8 serum levels, patients were followed for changes in uric acid and CXCL8
      levels. A subgroup analysis was performed in 10 patients with the longest follow
      up period and at least 4 assessments of serum uric acid and CXCL8. RESULTS: Sixty
      patients were included, and patients known with cardiovascular diseases at
      baseline had significantly higher CXCL8 and uric acid levels (P<0.01). In the
      whole group, median CXCL8 levels had not decreased after a median (IQR) follow-up
      of 27 (12-44) weeks (P=0.66). In the subgroup analysis in 9 out of 10 patients,
      CXCL8 levels showed a slight decrease, sometimes after an initial increase after
      a median (IQR) follow-up of 51 (45-60) weeks. CONCLUSIONS: This pilot study
      indicates that higher CXCL8 levels were associated cardiovascular diseases in
      gout patients. Short-term use of allopurinol does not decrease CXCL8 levels in
      gout patients, but longer use possibly does. Further studies are warranted to
      establish the potential mechanisms of treatment and effects on CXCL8 levels.

PMID- 27894952
TI  - Comparison of creatinine and cystatin C based eGFR in the estimation of
      glomerular filtration rate in Indigenous Australians: The eGFR Study.
AB  - BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equation that combines creatinine and cystatin C is superior to equations that
      include either measure alone in estimating glomerular filtration rate (GFR).
      However, whether cystatin C can provide any additional benefits in estimating GFR
      for Indigenous Australians, a population at high risk of end-stage kidney disease
      (ESKD) is unknown. METHODS: Using a cross-sectional analysis from the eGFR Study
      of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the
      CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and
      combined creatinine and cystatin C (eGFRcysC+cr). Reference GFR (mGFR) was
      determined using a non-isotopic iohexol plasma disappearance technique over 4h.
      Performance of each equation to mGFR was assessed by calculating bias, % bias,
      precision and accuracy for the total population, and according to age, sex,
      kidney disease, diabetes, obesity and c-reactive protein. RESULTS: Data were
      available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was
      significantly greater for eGFRcysC (15.0mL/min/1.73m2; 95% CI 13.3-16.4, p<0.001)
      and eGFRcysC+cr (10.3; 8.8-11.5, p<0.001) compared to eGFRcr (5.4; 3.0-7.2).
      Accuracy was lower for eGFRcysC (80.3%; 76.7-83.5, p<0.001) but not for
      eGFRcysC+cr (91.9; 89.3-94.0, p=0.29) compared to eGFRcr (90.0; 87.2-92.4).
      Precision was comparable for all equations. The performance of eGFRcysC
      deteriorated across increasing levels of c-reactive protein. CONCLUSION: Cystatin
      C based eGFR equations may not perform well in populations with high levels of
      chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the
      preferred equation in Indigenous Australians.

PMID- 27894953
TI  - Biological variability of lipoprotein-associated phospholipase A2 activity in
      healthy individuals.
AB  - OBJECTIVES: Measuring lipoprotein-associated phospholipase A2 (Lp-PLA2) activity
      can aid in identifying individuals at higher risk of coronary heart disease.
      However, the biological variation of Lp-PLA2 activity and corresponding reference
      change value (RCV) is unknown which limits interpretation of results. In this
      study we aim to define the intra- and inter-individual variability of Lp-PLA2
      activity in a healthy reference population. METHODS: A total of 24 healthy
      individuals (22-47years of age) were prospectively collected at several time
      points: daily for five days (after overnight fast), daily for three days (while
      non-fasting), weekly for four weeks (after overnight fast), and monthly for
      6months (after overnight fast). Intra-individual and inter-individual variability
      was determined. The index of individuality (IoI) and reference change value (RCV)
      were calculated for each time period. RESULTS: Variability in Lp-PLA2 activity
      was not different in fasting versus non-fasting states and also did not change in
      daily versus monthly testing. The RCV for monthly Lp-PLA2 activity was found to
      be 17%. More than 90% of the variability was attributable to between person
      differences while analytic variability comprised <9% of the variability and
      within-person variability was low at <0.7%. The index of individuality for
      monthly testing was 0.30 CONCLUSIONS: In a healthy population, Lp-PLA2 activity
      displays low analytical and within-person variability and higher inter-individual
      variability. The change required to differentiate a true change in patient status
      was determined to be 17% for monthly measurements. The between individual
      variability and corresponding RCV for the activity assay are lower than
      previously reported results for the Lp-PLA2 mass assay.

PMID- 27894954
TI  - Dual blocking of PI3K and mTOR signaling by NVP-BEZ235 inhibits proliferation in
      cervical carcinoma cells and enhances therapeutic response.
AB  - NVP-BEZ235 is a novel dual PI3K/mTOR inhibitor that shows dramatic effects on
      many tumors, but its effects on cervical carcinoma cells are largely unknown. In
      the present study, we investigated the effects of NVP-BEZ235 on the proliferation
      and invasion of cervical carcinoma cells in vitro and clarified its mechanism of
      action. In cellular settings with human cervical carcinoma cell lines, this
      molecule effectively and specifically blocked dysfunctional PI3K/mTOR pathway
      activation, suppressed cell growth in a time- and concentration-dependent manner,
      led to G1 cell cycle arrest, and induced apoptosis. NVP-BEZ235 suppressed HeLa
      cell invasiveness and metastasis by inhibiting the PI3K/Akt/MMP-2 pathway. We
      further demonstrated that NVP-BEZ235 treatment in combination with cisplatin or
      carboplatin induced a synergistic anti-tumoral response in cervical carcinoma
      cells. These findings suggested that NVP-BEZ235 could regulate growth and
      invasion of cervical carcinoma cells; thus it may provide a potential therapy for
      cervical carcinoma.

PMID- 27894955
TI  - Blocking preferential glucose uptake sensitizes liver tumor-initiating cells to
      glucose restriction and sorafenib treatment.
AB  - Cancer cells display altered metabolic phenotypes characterized by a high level
      of glycolysis, even under normoxic conditions. Because of a high rate of
      glycolytic flux and inadequate vascularization, tumor cells often suffer from
      nutrient deficiency and require metabolic adaptations to address such stresses.
      Although tumor-initiating cells (T-ICs) have been identified in various
      malignancies, the cells' metabolic phenotypes remain elusive. In this study, we
      observed that liver T-ICs preferentially survived under restricted glucose
      treatment. These cell populations compete successfully for glucose uptake by
      preferentially expressing glucose transporters (GLUT1 and GLUT3), whereas
      inhibition of GLUT1 or GLUT3 abolished the survival advantage and suppressed the
      tumorigenic potential of liver T-ICs. Among signaling pathways related to T-ICs,
      IL-6/STAT3 was identified to be responsible for the elevation of glucose uptake
      in liver T-ICs under glucose limitation. Further investigation revealed that IL-6
      stimulation upregulated GLUT1 and GLUT3 expressions in CD133+ cells, particularly
      during glucose deprivation. More importantly, inhibition of glucose uptake
      sensitized liver T-ICs to sorafenib treatment and enhanced the therapeutic
      efficacy in vivo. Our findings suggest that blocking IL-6/STAT3-mediated
      preferential glucose uptake might be exploited for novel therapeutic targets
      during hepatocellular carcinoma (HCC) progression.

PMID- 27894956
TI  - Disulfiram induces anoikis and suppresses lung colonization in triple-negative
      breast cancer via calpain activation.
AB  - Triple-negative breast cancers (TNBC) often exhibit an aggressive phenotype.
      Disulfiram (DSF) is an approved drug for the treatment of alcohol dependence, but
      has also been shown to kill TNBC cells in a copper (Cu)-dependent manner. Exactly
      how this occurs has not been clearly elucidated. We sought to investigate the
      mechanisms responsible for DSF/Cu-dependent induction of apoptosis and
      suppression of lung colonization by TNBC cells. DSF/Cu induced anoikis and
      significantly suppressed cell migration and invasion with negative effects on
      focal adhesions, coinciding with vimentin breakdown and calpain activation in
      TNBC cells. In a xenograft tumor model, DSF suppressed tumor growth and lung
      nodule growth, which was also associated with calpain activation. These findings
      warrant further investigation of disulfiram as a potential treatment for
      metastatic TNBC.

PMID- 27894958
TI  - Poly (ADP-ribose) polymerase inhibitors selectively induce cytotoxicity in TCF3
      HLF-positive leukemic cells.
AB  - Poly (ADP-ribose) polymerase (PARP) is an indispensable component of the DNA
      repair machinery. PARP inhibitors are used as cutting-edge treatments for
      patients with homologous recombination repair (HRR)-defective breast cancers
      harboring mutations in BRCA1 or BRCA2. Other tumors defective in HRR, including
      some hematological malignancies, are predicted to be good candidates for
      treatment with PARP inhibitors. Screening of leukemia-derived cell lines revealed
      that lymphoid lineage-derived leukemia cell lines, except for those derived from
      mature B cells and KMT2A (MLL)-rearranged B-cell precursors, were relatively
      sensitive to PARP inhibitors. By contrast, acute myelogenous leukemia cell lines,
      except for RUNX1-RUNXT1 (AML1-ETO)-positive lines, were relatively resistant.
      Intriguingly, TCF3 (E2A)-HLF-positive leukemia was sensitive to PARP inhibitors.
      TCF3-HLF expression suppressed HRR activity, suggesting that PARP inhibitor
      treatment induced synthetic lethality. Furthermore, TCF3-HLF expression decreased
      levels of MCPH1, which regulates the expression of BRCA1, resulting in
      attenuation of HRR activity. The PARP inhibitor olaparib was also effective in an
      in vivo xenograft model. Our results suggest a novel therapeutic approach for
      treating refractory leukemia, particularly the TCF3-HLF-positive subtype.

PMID- 27894957
TI  - DNA methylation profiling identifies PTRF/Cavin-1 as a novel tumor suppressor in
      Ewing sarcoma when co-expressed with caveolin-1.
AB  - Epigenetic modifications have been shown to be important in developmental tumors
      as Ewing sarcoma. We profiled the DNA methylation status of 15 primary tumors, 7
      cell lines, 10 healthy tissues and 4 human mesenchymal stem cells lines samples
      using the Infinium Human Methylation 450K. Differential methylation analysis
      between Ewing sarcoma and reference samples revealed 1166 hypermethylated and 864
      hypomethylated CpG sites (Bonferroni p < 0.05, delta-beta-value with absolute
      difference of >0.20) corresponding to 392 and 470 genes respectively. Gene
      Ontology analysis of genes differentially methylated in Ewing sarcoma samples
      showed a significant enrichment of developmental genes. Membrane and cell signal
      genes were also enriched, among those, 11 were related to caveola formation. We
      identified differential hypermethylation of CpGs located in the body and S-Shore
      of the PTRF gene in Ewing sarcoma that correlated with its repressed
      transcriptional state. Reintroduction of PTRF/Cavin-1 in Ewing sarcoma cells
      revealed a role of this protein as a tumor suppressor. Restoration of caveolae in
      the membrane of Ewing sarcoma cells, by exogenously reintroducing PTRF, disrupts
      the MDM2/p53 complex, which consequently results in the activation of p53 and the
      induction of apoptosis.

PMID- 27894960
TI  - Cancer stem cells in osteosarcoma.
AB  - Osteosarcoma is the most common primary bone tumour in children and adolescents
      and advanced osteosarcoma patients with evidence of metastasis share a poor
      prognosis. Osteosarcoma frequently gains resistance to standard therapies
      highlighting the need for improved treatment regimens and identification of novel
      therapeutic targets. Cancer stem cells (CSC) represent a sub-type of tumour cells
      attributed to critical steps in cancer including tumour propagation, therapy
      resistance, recurrence and in some cases metastasis. Recent published work
      demonstrates evidence of cancer stem cell phenotypes in osteosarcoma with links
      to drug resistance and tumorigenesis. In this review we will discuss the commonly
      used isolation techniques for cancer stem cells in osteosarcoma as well as the
      identified biochemical and molecular markers.

PMID- 27894961
TI  - Low-dose norfloxacin and ciprofloxacin therapy worsen leptospirosis in hamster.
AB  - Antibiotics play an important role in the treatment of leptospirosis. Many
      antibiotics at appropriate concentrations improved the survival rate and
      alleviated tissue injury, while, when dosing strategies fall below subtherapeutic
      levels, worse therapeutic effects are seen. In the present study, we investigated
      the efficacy of low-dose norfloxacin (10, 20 and 30 mg/kg) and ciprofloxacin (1,
      2 and 5 mg/kg) against leptospirosis in a hamster model using Leptospira
      interrogans serovar Icterohaemorrhagiae. The histopathology and bacterial loads
      of target organs (liver, kidney and lung) were also studied by treatment with
      norfloxacin at the dose of 10 mg/kg in this model. Using RT-PCR, the expression
      of inflammatory factor IL-1beta and TNF-alpha was analyzed by comparing the
      norfloxacin and untreated group. All untreated animals, serving as a negative
      control, displayed 50% survival rate, while hamsters treated with norfloxacin at
      the dose of 10 and 20 mg/kg and ciprofloxacin at the dose of 1 and 2 mg/kg showed
      a lower survival rate than the untreated group. Furthermore, norfloxacin at the
      dose of 10 mg/kg increased bacterial loads and aggravated tissue injury of target
      organs. The delayed induction of IL-1beta and TNF-alpha was found in tissues of
      norfloxacin group. Our study indicates an increased risk associated with low-dose
      norfloxacin and ciprofloxacin in leptospirosis.

PMID- 27894959
TI  - Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma
      growth.
AB  - PURPOSE: Cholangiocarcinoma (CCA) is a malignancy of the biliary epithelium that
      is associated with low five-year survival. The apelin receptor (APLNR), which is
      activated by the apelin peptide, has not been studied in CCA. The purpose of this
      study is to determine if inhibition of the apelin/APLNR axis can inhibit CCA
      growth. METHODS: Immunohistochemistry, rtPCR, immunofluorescence, flow cytometry,
      and ELISA was used to measure APLNR expression in human CCA cells and tissues. Mz
      ChA-1 cells were treated with increasing concentrations of apelin and ML221, an
      APLNR antagonist. Expression of proliferative and angiogenic genes were measured
      via rtPCR. In vivo, Mz-ChA-1 cells were injected into the flanks of nu/nu mice,
      which were treated with ML221 (150 MUg/kg) via tail vein injection. RESULTS:
      Expression of the apelin/APLNR axis was increased in CCA. In vitro, CCA
      proliferation and angiogenesis was inhibited by ML221 treatment. ML221 treatment
      significantly decreased tumor growth in nu/nu mice. CONCLUSION: The apelin/APLNR
      axis regulates CCA proliferation and angiogenesis. Inhibition of the apelin/APLNR
      axis decreases tumor growth in our xenograft model. Targeting APLNR signaling has
      the potential to serve as a novel, tumor directed therapy for CCA.

PMID- 27894963
TI  - Longitudinal surveillance on antibiogram of important Gram-positive pathogens in
      Southern China, 2001 to 2015.
AB  - OBJECTIVES: A longitudinal surveillance aimed to investigate the antibiogram of
      three genus of important Gram-positive pathogens in Southern China during 2001
      2015. METHODS: A total of 3849 Staphylococcus, Enterococcus and Streptococcus
      strains were isolated from Southern China during 2001-2015. Bacteria
      identification was performed by colony morphology, Gram staining, the API
      commercial kit and the Vitek 2 automated system. Antimicrobial susceptibility
      testing was determined by disk diffusion method and MIC method. RESULTS: As
      sampling site was concerned, 51.4% of Staphylococcus strains were isolated from
      sputum, whereas urinary tract remained the dominant infection site among
      Enterococcus and Streptococcus. According to the antimicrobial susceptibility,
      three genus of important Gram-positive pathogens showed high resistance against
      erythromycin, tetracycline, ciprofloxacin and clindamycin. Resistance rates to
      penicillins (penicillin, oxacillin, ampicillin) were high as well, with the
      exception of E. faecalis and Streptococcus. Overall, resistance rates against
      methicillin (oxacillin) were 63.2% in S. aureus and 76.2% in coagulase-negative
      Staphylococcus (CNS), along with continuous increases during the study. VRSA and
      vancomycin-resistant coagulase-negative Staphylococcus only appeared in 2011
      2015. Sight decline was obtained for the vancomycin resistance of E. faecalis,
      while vancomycin-resistant E. faecium only appeared in 2011-2015, with its
      intermediate rate decreasing. Significant decrease in penicillin-resistant
      Streptococcus pneumonia (PRSP) was observed during studied period. Glycopeptide
      antibiotic remained highly effective to Staphylococcus, Enterococcus and
      Streptococcus (resistance rates <5%). CONCLUSIONS: Despite decline obtained for
      some antibiotic agents resistance during 2001-2015, antimicrobial resistance
      among Gram-positive pathogens still remained high in Southern China. This study
      may aid in the guidance for appropriate therapeutic strategy of infections caused
      by nosocomial pathogens.

PMID- 27894962
TI  - Clinico-pathology and hemato-biochemistry responses in buffaloes infected with
      Pasteurella multocida type B:2 immunogen outer membrane protein.
AB  - The aim of this study was to investigate the clinico-pathology and haemato
      biochemistry alterations in buffaloes inoculated with Pasteurella multocida type
      B:2 immunogen outer membrane protein via subcutaneous and oral routes. Nine
      buffalo heifers were divided equally into 3 treatment groups. Group 1 was
      inoculated orally with 10 mL of phosphate buffer saline (PBS); Group 2 and 3 were
      inoculated with 10 mL of outer membrane protein broth subcutaneously and orally
      respectively. Group 2 buffaloes showed typical haemorrhagic septicaemia clinical
      signs and were only able to survive for 72 h of the experiment. However, Group 3
      buffaloes were able to survive throughout the stipulated time of 21 days of
      experiment. There were significant differences (p < 0.05) in the rectal
      temperature between the experimental and control group. In the hematology and
      biochemistry findings, there were significant differences (p < 0.05) in packed
      cell volume, mean corpuscular volume, mean corpuscular haemoglobin concentration,
      leukocytes, band neutrophils, segmented neutrophils, lymphocytes, eosinophils,
      basophils, gamma glutamyl transferase, total protein, and globulin between Group
      2 and control group. In contrast, Group 3 and control group revealed significant
      differences (p < 0.05) in erythrocytes, haemoglobin, mean corpuscular haemoglobin
      concentration, segmented neutrophils, lymphocytes, monocytes, eosinophils,
      basophils, thrombocytes, gamma glutamyl transferase, total protein, globulin, and
      albumin:globulin ratio. In Group 2 buffaloes, there were gross lesions observed
      in the lung, trachea, heart, liver, spleen, kidney and submandibulae lymph nodes.
      In contrast, lesions were only observed in the lung, and liver of Group 3
      buffaloes. There were significant differences (p < 0.05) in hemorrhage and
      congestion; necrosis and degeneration; and inflammatory cells infiltration
      between experimental groups and control group. However, there were no significant
      differences (p > 0.05) in edema between groups except for the lung. This study
      was a proof that oral route infection of Pasteurella multocida type B:2 immunogen
      outer membrane protein can be used to stimulate host cell.

PMID- 27894964
TI  - Approach to osteomyelitis treatment with antibiotic loaded PMMA.
AB  - BACKGROUND: To reduce the incidence of osteomyelitis infection, local antibiotic
      impregnated delivery systems are commonly used as a promising and effective
      approach to deliver high antibiotic concentrations at the infection site.
      OBJECTIVE: The objective of this review was to provide a literature review
      regarding approach to osteomyelitis treatment with antibiotic loaded PMMA. STUDY
      DESIGN: Literature study regarding osteomyelitis treatment with antibiotic loaded
      carriers using key terms Antibiotic, osteomyelitis, biodegradable PMMA through
      published articles. Hands searching of bibliographies of identified articles were
      also undertaken. CONCLUSION: We concluded that Antibiotic-impregnated PMMA beads
      are useful options for the treatment of osteomyelitis for prolonged drug therapy.

PMID- 27894965
TI  - An application of mass spectrometry for quality control of biologicals: Highly
      sensitive profiling of plasma residuals in human plasma-derived immunoglobulin.
AB  - : Thromboembolic events (TEE) associated to trace amounts of plasmatic activated
      coagulation factor XI (FXIa) in administrated immunoglobulin (Ig) have recently
      raised concerns and hence there is a need for highly sensitive profiling of
      residual plasma source proteins. This study aims to consider LC-ESI-QTOF data
      dependent acquisition in combination with sample fractionation for this purpose.
      Sample fractionation proved mandatory to enable identification of plasma
      residuals. Two approaches were compared: Ig depletion with protein G - protein A
      affinity chromatography and low-abundant protein enrichment with a combinatorial
      peptide ligand library (ProteoMinerTM, Bio-Rad). The latter allowed a higher
      number of identifications. Highly sensitive detection of prothrombotic FXIa was
      assessed with confident identification of a 1ng/mg spike. Moreover, different
      residuals compositions were profiled for various commercial Ig products. Using a
      quantitative label free analysis, a TEE-positive Ig batch was distinguished from
      other regular Ig products, with increased levels of FXIa but also other unique
      proteins. This could have prevented the recently observed TEE problems with Ig.
      The method is a convenient tool to better characterize Ig products after any
      plasma pool or manufacture process change, gaining insights in the product
      quality profile without any prior information required. BIOLOGICAL SIGNIFICANCE:
      This study characterized residual plasma proteins in Ig products, using bottom-up
      LC-MS/MS with conventional data-dependent acquisition, preceded by sample
      fractionation. Without any prior information or target-specific development, >30
      proteins were identified in a commercial Ig product. Quality control relevance
      was demonstrated with the identification of FXIa spiked at 1ng/mg in Ig, which is
      below the minimal thrombotic dose of 3ng/mg observed in an in vivo model.
      Relative label-free quantitation highlighted significant differences in
      normalized abundances of residual proteins between Ig products. A TEE-positive
      batch was distinguished by unique profile of residual proteins, including FXIa
      but also various blood stream-regulator proteins (fibrinogen, angiotensinogen,
      antithrombin-III, complement component C8, ...). Those results emphasize that MS
      screening is a relevant first-line test to prevent any undesired concentration of
      plasma impurities after a plasma pool or manufacturing process change.

PMID- 27894966
TI  - Quantitative proteomic changes during post myocardial infarction remodeling
      reveals altered cardiac metabolism and Desmin aggregation in the infarct region.
AB  - : Myocardial infarction is one of the leading causes of cardiac dysfunction,
      failure and sudden death. Post infarction cardiac remodeling presents a poor
      prognosis, with 30%-45% of patients developing heart failure, in a period of 5
      25years. Oxidative stress has been labelled as the primary causative factor for
      cardiac damage during infarction, however, the impact it may have during the
      process of post infarction remodeling has not been well probed. In this study, we
      have implemented iTRAQ proteomics to catalogue proteins and functional processes,
      participating both temporally (early and late phases) and spatially (infarct and
      remote zones), during post myocardial infarction remodeling of the heart as
      functions of the differential oxidative stress manifest during the remodeling
      process. Cardiac metabolism was the dominant network to be affected during
      infarction and the remodeling time points considered in this study. A distinctive
      expression pattern of cytoskeletal proteins was also observed with increased
      remodeling time points. Further, it was found that the cytoskeletal protein
      Desmin, aggregated in the infarct zone during the remodeling process, mediated by
      the protease Calpain1. Taken together, all of these data in conjunction may lay
      the foundation to understand the effects of oxidative stress on the remodeling
      process and elaborate the mechanism behind the compromised cardiac function
      observed during post myocardial infarction remodeling. SIGNIFICANCE: Oxidative
      stress is the major driving force for cardiac damage during myocardial
      infarction. However, the impact of oxidative stress on the process of post MI
      remodeling in conducting the heart towards functional failure has not been well
      explored. In this study, a spatial and temporal approach was taken to elaborate
      the major proteins and cellular processes involved in post MI remodeling. Based
      on level/ intensity of ROS, spatially, infarct and noninfarct zones were chosen
      for analysis while on the temporal scale, early (30days) and late time points
      (120days) post MI were included in the study. This design enabled us to delineate
      the differential protein expression on a spectrum of maximum oxidative stress at
      infarct zone during MI to minimum oxidative stress at noninfarct zone during late
      time point post MI. The proteome profiles for each of the study groups when
      comparatively analysed gave a holistic idea about the dominant cellular processes
      involved in post MI remodeling such as cardiac metabolism, both for short term
      and long term remodeling as well as unique processes such as Desmin mediated
      cytoskeletal remodeling of the infarcted myocardium that are involved in the
      compromise of cardiac function.

PMID- 27894967
TI  - Role of Buffers in Protein Formulations.
AB  - Buffers comprise an integral component of protein formulations. Not only do they
      function to regulate shifts in pH, they also can stabilize proteins by a variety
      of mechanisms. The ability of buffers to stabilize therapeutic proteins whether
      in liquid formulations, frozen solutions, or the solid state is highlighted in
      this review. Addition of buffers can result in increased conformational stability
      of proteins, whether by ligand binding or by an excluded solute mechanism. In
      addition, they can alter the colloidal stability of proteins and modulate
      interfacial damage. Buffers can also lead to destabilization of proteins, and the
      stability of buffers themselves is presented. Furthermore, the potential safety
      and toxicity issues of buffers are discussed, with a special emphasis on the
      influence of buffers on the perceived pain upon injection. Finally, the
      interaction of buffers with other excipients is examined.

PMID- 27894968
TI  - Crystallographic Structure, Intermolecular Packing Energetics, Crystal Morphology
      and Surface Chemistry of Salmeterol Xinafoate (Form I).
AB  - Single crystals of salmeterol xinafoate (form I), prepared from slow cooled
      supersaturated propan-2-ol solutions, crystallize in a triclinic P1- symmetry
      with 2 closely related independent salt pairs within the asymmetric unit, with an
      approximately double-unit cell volume compared with the previously published
      crystal structure. Synthonic analysis of the bulk intermolecular packing confirms
      the similarity in packing energetics between the 2 salt pairs. The strongest
      synthons, as expected, are dominated by coulombic interactions. Morphologic
      prediction reveals a plate-like morphology, dominated by the {001}, {010}, and
      {100} surfaces, consistent with experimentally grown crystals. Although surface
      chemistry of the slow-growing {001} face comprises large sterically hindering
      phenyl groups, although weaker coulombic interactions still prevail from the
      alcohol group present on the phenyl and hydroxymethyl groups. The surface
      chemistry of the faster growing {010} and {100} faces are dominated by the
      significantly stronger cation/anion interactions occurring between the
      carboxylate and protonated secondary ammonium ion groups. The importance of
      understanding the cohesive and adhesive nature of the crystal surfaces of an
      active pharmaceutical ingredient, with respect to their interaction with other
      active pharmaceutical ingredient crystals and how that may affect formulation
      design, is highlighted.

PMID- 27894969
TI  - The types and aspects of front-of-pack food labelling schemes preferred by adults
      and children.
AB  - There is strong interest in front-of-pack labels (FoPLs) as a potential mechanism
      for improving diets, and therefore health, at the population level. The present
      study examined Australian consumers' preferences for different types and
      attributes of FoPLs to provide additional insights into optimal methods of
      presenting nutrition information on the front of food packets. Much research to
      date has focused on two main types of FoPLs - those expressing daily intake
      values for specific nutrients and those utilising 'traffic light' colour coding.
      This study extends this work by: (i) including the new Health Star Rating system
      recently introduced in Australia and New Zealand; (ii) allowing a large sample of
      consumers to self-nominate the evaluation criteria they consider to be most
      important in choosing between FoPLs; (iii) oversampling consumers of lower
      socioeconomic status; and (iv) including children, who consume and purchase food
      in their own right and also influence their parents' food purchase decisions. A
      cross-sectional online survey of 2058 Australian consumers (1558 adults and 500
      children) assessed preferences between a daily intake FoPL, a traffic light FoPL,
      and the Health Star Rating FoPL. Across the whole sample and among all respondent
      subgroups (males vs females; adults vs children; lower socioeconomic status vs
      medium-high socioeconomic status; normal weight vs overweight/obese), the Health
      Star Rating was the most preferred FoPL (44%) and the daily intake guide was the
      least preferred (20%). The reasons most commonly provided by respondents to
      explain their preference related to ease of use, interpretive content, and
      salience. The findings suggest that a simple to use, interpretive, star-based
      food label represents a population-based nutrition promotion strategy that is
      considered helpful by a broad range of consumers.

PMID- 27894970
TI  - Genome-wide characterization of the SiDof gene family in foxtail millet (Setaria
      italica).
AB  - Dof (DNA binding with one finger) proteins, which constitute a class of
      transcription factors found exclusively in plants, are involved in numerous
      physiological and biochemical reactions affecting growth and development. A
      genome-wide analysis of SiDof genes was performed in this study. Thirty five
      SiDof genes were identified and those genes were unevenly distributed across nine
      chromosomes in the Seteria italica genome. Protein lengths, molecular weights,
      and theoretical isoelectric points of SiDofs all vary greatly. Gene structure
      analysis demonstrated that most SiDof genes lack introns. Phylogenetic analysis
      of SiDof proteins and Dof proteins from Arabidopsis thaliana, rice, sorghum, and
      Setaria viridis revealed six major groups. Analysis of RNA-Seq data indicated
      that SiDof gene expression levels varied across roots, stems, leaves, and spike.
      In addition, expression profiling of SiDof genes in response to stress suggested
      that SiDof 7 and SiDof 15 are involved in drought stress signalling. Overall,
      this study could provide novel information on SiDofs for further investigation in
      foxtail millet.

PMID- 27894971
TI  - Aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (Apocynaceae)
      palliates hyperglycemia, insulin resistance, dyslipidemia, inflammation and
      oxidative stress in high-fructose diet-induced metabolic syndrome in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Hunteria umbellata is used in the management and
      treatment of diabetes and obesity in Nigeria. This study evaluates the effect of
      aqueous seed extract of Hunteria umbellata on insulin resistance, dyslipidemia,
      inflammation and oxidative stress in high-fructose diet-induced metabolic
      syndrome MATERIALS AND METHODS: Rats were randomized into seven groups (A-G).
      Control (group A) and group C rats received control diet for nine weeks while
      rats in groups B, D - G were placed on high-fructose diet for 9 weeks. In
      addition to the diets, groups C - F rats orally received 400, 100, 200 and
      400mg/kg body weight aqueous seed extract of Hunteria umbellata for 3 weeks
      starting from 6th - 9th week. RESULTS: High-fructose diet (when compared to
      control rats) mediated a significant (p<0.05) increase in body weight, body mass
      index and abdominal circumference. Similarly, levels of blood glucose, insulin,
      leptin, adiponectin and insulin resistance were increased. It also caused a
      significant increase in the levels of cholesterol, triglycerides, low-density
      lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic
      index, cardiac index and coronary artery index while high-density lipoprotein
      cholesterol was decreased significantly. Levels of proinflammatory factor, tumour
      necrosis factor-alpha, interleukin-6 and 8 were also increased by the high
      fructose diet. Moreover, it mediated decrease in activities of superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6
      phosphate dehydrogenase and level of glutathione reduced. Conversely, levels of
      malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and
      fragmented DNA were elevated. Aqueous seed extract of Hunteria umbellata
      significantly ameliorated the high fructose diet-mediated alterations.
      CONCLUSIONS: From this study, it is concluded that aqueous seed extract of
      Hunteria umbellata possesses hypoglycemic, hypolipidemic and antioxidants
      abilities as evident from its capability to extenuate insulin resistance,
      dyslipidemia, inflammation and oxidative stress in high-fructose diet-induced
      metabolic syndrome rats.

PMID- 27894972
TI  - Transcriptome inference and systems approaches to polypharmacology and drug
      discovery in herbal medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine is a concoction of numerous
      chemical ingredients, and it exhibits polypharmacological effects to act on
      multiple pharmacological targets, regulating different biological mechanisms and
      treating a variety of diseases. Thus, this complexity is impossible to
      deconvolute by the reductionist method of extracting one active ingredient acting
      on one biological target. AIM OF THE STUDY: To dissect the polypharmacological
      effects of herbal medicines and their underling pharmacological targets as well
      as their corresponding active ingredients. MATERIALS AND METHODS: We propose a
      system-biology strategy that combines omics and bioinformatical methodologies for
      exploring the polypharmacology of herbal mixtures. The myocardial ischemia model
      was induced by Ameroid constriction of the left anterior descending coronary in
      Ba-Ma miniature pigs. RNA-seq analysis was utilized to find the differential
      genes induced by myocardial ischemia in pigs treated with formula QSKL. A
      transcriptome-based inference method was used to find the landmark drugs with
      similar mechanisms to QSKL. RESULTS: Gene-level analysis of RNA-seq data in QSKL
      treated cases versus control animals yields 279 differential genes. Transcriptome
      based inference methods identified 80 landmark drugs that covered nearly all drug
      classes. Then, based on the landmark drugs, 155 potential pharmacological targets
      and 57 indications were identified for QSKL. CONCLUSION: Our results demonstrate
      the power of a combined approach for exploring the pharmacological target and
      chemical space of herbal medicines. We hope that our method could enhance our
      understanding of the molecular mechanisms of herbal systems and further
      accelerate the exploration of the value of traditional herbal medicine systems.

PMID- 27894973
TI  - Is there nothing new under the sun? The influence of herbals and pharmacopoeias
      on ethnobotanical traditions in Albacete (Spain).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This paper has two overarching aims: (1)
      presenting the results of studying the Albacete tariff of medicines of 1526 and
      (2) broadly analyzing the origin and influences of medicinal traditional
      knowledge in the region of Albacete, Spain. We use historical and modern
      literature that may have influenced this knowledge. Our primary goal was to
      determine the ingredients used in the pharmacy in the 16th century CE in Albacete
      through the analysis of the tariff, and our secondary goal was to investigate
      until when ingredients and uses present in pharmacy and herbals persisted in
      later periods. METHODS: The identity of medicines and ingredients was determined
      by analyzing contemporary pharmacopoeias and classical pharmaceutical references.
      We analyzed further 21 sources (manuscripts, herbals, and books of medicines,
      pharmacopoeias, pharmacy inventories, and modern ethnobotanical records) for the
      presence/absence of ingredients and complex formulations of the tariff. Using
      factorial and cluster analysis and Bayesian inference applied to evolution models
      (reversible-jump Markov chain Monte Carlo), we compared textual sources. Finally,
      we analyzed the medicinal uses of the top 10 species in terms of frequency of
      citation to assess the dependence of modern ethnobotanical records on Renaissance
      pharmacy and herbals, and, ultimately, on Dioscorides. RESULTS: In Albacete 1526,
      we determined 101 medicines (29 simple drugs and 72 compound medicines)
      comprising 187 ingredients (85% botanical, 7.5% mineral, and 7.5% zoological
      substances). All composed medicines appear standardized in the pharmacopoeias,
      notably in the pharmacopoeia of Florence from 1498. However, most were no longer
      in use by 1750 in the pharmacy, and were completely absent in popular herbal
      medicine in Albacete 1995 as well as in Alta Valle del Reno (Italy) in 2014.
      Among the ingredients present in different formulation are the flowers of Rosa
      gallica, honey (Apis mellifera), the roots of Nardostachys jatamansi, and
      Convolvulus scammonia, pistils of Crocus sativus, grapes and raisins (Vitis
      vinifera), rhizomes of Zingiber officinale, bark of Cinnamomum verum, leaves and
      fruits of Olea europaea, mastic generally of Pistacia lentiscus, and wood of
      Santalum album. The statistical analysis of sources produces four well-separated
      clusters (Renaissance Herbals and Pharmacopoeias, Ethnobotany and Folk Medicine,
      Old phytotherapy, and Modern phytotherapy including Naturopathy) confirming our a
      priori classification. The clade of Renaissance Herbals and Pharmacopoeias
      appears separated from the rest in 97% of bootstrapped trees. Bayesian inference
      produces a tree determined by an initial set of two well-distinct core groups of
      ingredients: 64, locally used in Mediterranean Europe during centuries; and 45,
      imported, used in pharmacy during centuries. Complexity reached its maximum in
      Albacete 1526 and contemporary pharmacopoeias, gradually decreasing over time.
      The analysis of medicinal uses of the top 10 ingredients showed low coincidence
      between Dioscorides and different Renaissance herbals or medical treatises and of
      all of them with ethnobotany in Albacete. CONCLUSIONS: Regarding our question: is
      there something new under the sun? In some aspects, the answer is "No". The
      contrast between expensive drugs, highly valued medicines, and unappreciated
      local wild medicinal plants persists since the Salerno's school of medicine. Old
      medicine in Mediterranean Europe, as reflected by Albacete 1526 tariff of
      medicines, involved strict formulations and preferences for certain ingredients
      despite other ingredients locally available but underappreciated. This confirms
      the fact that any system of medicine does not get to use all available resources.
      Ethnobiological records of materia medica, in rural areas of Albacete, describe
      systems with a high degree of stability and resilience, where the use of local
      resources, largely wild but also cultivated, is predominant in contrast with the
      weight of imported exotic products in pharmacy.

PMID- 27894974
TI  - Cell-cycle Progression-score Might Improve the Current Risk Assessment in Newly
      Diagnosed Prostate Cancer Patients.
AB  - OBJECTIVE: To assess whether cell-cycle progression (CCP)-score (Prolaris) can
      improve the current risk assessment in newly diagnosed prostate cancer (PCa)
      patients. CCP-score is a well-validated prognostic assay predictive of PCa death,
      biochemical recurrence, and progression. METHODS: We evaluated CCP-score at
      biopsy in 52 patients newly diagnosed with PCa who underwent radical
      prostatectomy. CCP-score was calculated as average RNA expression of 31 CCP
      genes, normalized to 15 housekeeping genes. The predictive ability of CCP-score
      was assessed in univariate and multivariate analyses, and compared to that of Ki
      67 levels and traditional clinical variables including prostate-specific antigen,
      Gleason score, stage, and percentage of positive cores at biopsy. RESULTS: In
      spite of an overall good accuracy in attributing the correct risk class, 7 high
      risk and 13 intermediate-risk patients were misclassified by the Prolaris test.
      On analysis of variance, mean CCP-score significantly differed across different
      risk classes based on pathologic results (-1.2 in low risk, -0.444 in
      intermediate risk, 0.208 in high risk). CCP-score was a significant predictor of
      high-risk PCa both on univariate and multivariate analyses, after adjusting for
      clinical variables. Combining CCP-score and the European Association of Urology
      clinical risk assessment improved the accuracy of risk attribution by around 10%,
      up to 87.8%. CCP-score was a significant predictor of biochemical recurrence, but
      only on univariate analysis. CONCLUSION: The CCP-score might provide important
      new information to risk assessment of newly diagnosed PCa in addition to
      traditional clinical variables. A correct risk attribution is essential to tailor
      the best treatment for each patient.

PMID- 27894975
TI  - Re: Lopes et al.: "Zero-Ischemia" Laparoscopic-assisted Partial Nephrectomy for
      the Management of Selected Children With Wilms Tumors Following Neoadjuvant
      Chemotherapy. (Urology 2017;100:103-110).

PMID- 27894976
TI  - Comparison of the Clinical Outcomes of Intracytoplasmic Sperm Injection Between
      Spermatozoa Retrieved From Testicular Biopsy and From Ejaculate in
      Cryptozoospermia Patients.
AB  - OBJECTIVE: To compare the clinical outcomes of intracytoplasmic sperm injection
      (ICSI) between spermatozoa retrieved from testicular biopsy and from ejaculate in
      cryptozoospermia patients. MATERIALS AND METHODS: The clinical data of 285
      cryptozoospermia patients who underwent ICSI treatment in our center during the
      period from March 2009 to November 2013 were retrospectively analyzed. Within
      them, ejaculated sperms were used in 214 cases (group 1), and testicular sperms
      extracted by testicular sperm aspiration or conventional testis dissection sperm
      extraction were used in 71 cases (group 2). Good-quality embryo, fertilization,
      embryo implantation, pregnancy, and birth rates after ICSI were compared between
      the 2 groups. RESULTS: Comparing the ejaculated sperm group with the testicular
      sperm group, fertilization rates were 59.6% and 60.6%, good-quality embryo rates
      were 36.8% and 46.1%, embryo implantation rates were 30.7% and 52.1%, pregnancy
      rates were 33.3% and 53.6%, and birth rates were 27.1% and 44.6%, respectively.
      CONCLUSION: Using testicular sperms can achieve higher rates of embryo
      implantation, pregnancy, and birth compared with those using ejaculated sperms
      for ICSI treatment in cryptozoospermia patients.

PMID- 27894977
TI  - Granular Cell Tumor of the Bladder: A Rare Neoplasm Managed With Robotic Partial
      Cystectomy Using Near-infrared Filter Guidance.

PMID- 27894978
TI  - An Arterial Perihepatic Enhancement Caused by Spontaneous Bladder Rupture.
AB  - Spontaneous bladder rupture (SBR) is a rare but life-threatening condition. Its
      diagnosis is challenging; symptoms might present solely as ascites during onset
      or with features of frank peritonitis. When SBR causes peritonitis, arterial
      perihepatic enhancement can be detected on a contrast computed tomography scan.
      SBR should be suspected when patients have acute abdominal pain and risk factors
      including previous pelvic irradiation, urethral catheterization, and binge
      alcohol drinking. We present the first case report of arterial perihepatic
      enhancement due to SBR.

PMID- 27894979
TI  - Comparison of White Light, Photodynamic Diagnosis, and Narrow-band Imaging in
      Detection of Carcinoma In Situ or Flat Dysplasia at Transurethral Resection of
      the Bladder: the DaBlaCa-8 Study.
AB  - OBJECTIVE: To compare findings in NBI to findings in WL and PDD in a high-risk
      patient population. MATERIALS AND METHODS: A total of 171 patients were included
      in the study from 4 different urology departments in Denmark and Norway. Patients
      were scheduled for a PDD-guided transurethral tumor resection or cystoscopy
      guided biopsy in accordance with Danish guidelines, on the suspicion of primary
      or concomitant CIS. All patients were examined with WL cystoscopy followed by
      both NBI and PDD before biopsy. RESULTS: A total of 136 patients were biopsied
      due to findings with suspicion of CIS in at least 1 modality (482 biopsies with a
      mean of 3.5 biopsies per patient). Analysis at patient level showed that NBI and
      PDD had a significantly higher sensitivity regarding identification of CIS and
      dysplasia compared with WL (NBI: 95.7%, PDD: 95.7% vs WL: 65.2%, P < .05).
      Specificity was not significantly different between the 3 methods (NBI: 52.0%,
      PDD: 48.0%, and WL: 56.8%). When analyzed per biopsy, NBI and PDD had a
      significantly higher sensitivity than WL (NBI: 72.7% and PDD: 78.2% vs WL: 52.7%,
      P < .05), whereas the positive predictive values were not significantly different
      (NBI: 23.7%, PDD: 22.2%, and WL: 19.0%). CONCLUSION: NBI was found to be a valid
      alternative to PDD regarding diagnosis of CIS and flat dysplasia.

PMID- 27894981
TI  - HIV prevalence among men who have sex with men in Istanbul.
AB  - OBJECTIVES: The re-emergence of the HIV epidemic among men who have sex with men
      (MSM) represents a serious health issue. This study aimed to assess the HIV
      prevalence among MSM in a very low prevalence population of a large city.
      METHODS: A public campaign to raise awareness of HIV infection and to provide
      access to anonymous testing was conducted in places frequented by MSM and through
      a mobile phone application. No identity information was requested from
      individuals contacting the call centre, and anonymous and free HIV testing was
      offered proactively. Those who agreed to have a test were provided a code number,
      which was used in blood sampling procedures. RESULTS: Of 1200 subjects who
      contacted the call centre, 197 consented to undergo HIV testing and visited the
      laboratory to give a blood sample. Twenty-five subjects were found to have a
      reactive ELISA result on two different occasions plus a positive Western blot
      test result. Thus, the HIV prevalence in this group of MSM was 12.7%.
      CONCLUSIONS: MSM remain a high risk group for HIV infection in a low prevalence
      setting, and thus represent a key target population for diagnostic and
      therapeutic interventions.

PMID- 27894982
TI  - Multiple Opportunistic Infections in a Woman with GATA2 Mutation.
AB  - GATA2 deficiency is a genetic disorder caused by inherited or sporadic
      haploinsufficient mutations in the GATA2 gene. Patients have abnormalities in
      hematopoiesis, lymphangiogenesis and immunity; encompassing a broad range of
      clinical syndromes, mainly characterized by monocytopenia, B and NK cell
      cytopenia, severe or recurrent infections, and a high risk of developing
      myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). We report a case
      of an Argentinean woman who presented with multiple opportunistic infections as
      her first manifestation of GATA2 deficiency.

PMID- 27894983
TI  - A case of clinical and microbiological failure of azithromycin therapy in
      Salmonella enterica serotype Typhi despite low azithromycin MIC.
AB  - Typhoid fever remains a serious problem in many developing countries. Due to
      resistance to multiple first line drugs, azithromycin has evolved as an important
      drug in the treatment of typhoid. While therapy with azithromycin is highly
      effective, no clinically validated mean inhibitory concentration (MIC) break
      points or disc diffusion cutoff guidelines are available so far. We describe an
      Indian adult with clinical and microbiological failure to azithromycin despite
      low azithromycin MIC.

PMID- 27894984
TI  - A longitudinal analysis of methicillin-resistant and sensitive Staphylococcus
      aureus incidence in respect to specimen source, patient location, and temperature
      variation.
AB  - OBJECTIVE: Seasonal variations in temperature exert strong selective pressure on
      microorganism population dynamics and should be taken into account in
      epidemiological studies. The objective of the present study was to characterize
      the seasonal variation of staphylococcal infections in respect to patient
      location, specimen source, month of year, and temperature variation. METHODS: A
      retrospective longitudinal time-series analysis of methicillin-resistant and
      methicillin-sensitive Staphylococcus aureus (MRSA and MSSA) was conducted in
      northeastern Ohio over a 5-year period. Multivariable time-series analyses were
      performed to detect the variations in the monthly incidence based on location of
      patients (inpatient, outpatient, and nursing homes), source of specimen (wound,
      respiratory tract, and urine), time of year (January-December), and temperature
      variation (average monthly over 5 years). RESULTS: The results indicated a
      gradual increase in both MRSA and MSSA infections, with outpatient cases
      representing the majority of cases. If present, the seasonal nature of MRSA
      infections varied based on specimen source and patient location, with wound
      infections from outpatients more prevalent in warmer months, and respiratory
      infections among inpatients more prevalent during colder months. CONCLUSIONS: The
      current report provides a longitudinal analysis of staphylococcal epidemiology,
      and in the process, identifies the seasonal nature of infections to be
      multifactorial, depending on such variables as specimen source and patient
      location. The seasonal nature of staphylococcal infections appears to be the
      product of a complex interaction among host, pathogen, and environment.

PMID- 27894985
TI  - Factors influencing treatment default among tuberculosis patients in a high
      burden province of South Africa.
AB  - OBJECTIVE: To determine and describe the factors influencing treatment default of
      tuberculosis (TB) patients in the Free State Province of South Africa. METHODS: A
      retrospective records review of pulmonary TB cases captured in the ETR.Net
      electronic TB register between 2003 and 2012 was performed. Subjects were >15
      years of age and had a recorded pre-treatment smear result. The demographic and
      clinical characteristics of defaulters were described. Multivariate logistic
      regression analysis was used to determine factors associated with treatment
      default. The odds ratios (OR) together with their corresponding 95% confidence
      intervals (CI) were estimated. Statistical significance was considered at 0.05.
      RESULTS: A total of 7980 out of 110 349 (7.2%) cases defaulted treatment.
      Significantly higher proportions of cases were male (8.3% vs. female: 5.8%;
      p<0.001), <25 years old (9.1% vs. 25-34 years: 8.7%; 35-44 years: 7.0%; 45-54
      years: 5.2%; 55-64 years: 4.4%; >64 years: 3.9%; p<0.001), undergoing TB
      retreatment (11.0% vs. new cases: 6.3%; p<0.001), had a negative pre-treatment
      sputum smear result (7.8% vs. positive smear results: 7.1%; p<0.001), were in the
      first 2 months of treatment (95.5% vs. >2 months: 4.8%; p<0.001), and had unknown
      HIV status (7.8% vs. HIV-positive: 7.0% and HIV-negative: 5.7%; p<0.001). After
      controlling for potential confounders, multivariate analysis revealed a two-fold
      increased risk of defaulting treatment when being retreated compared to being
      treated for the first time for TB (adjusted OR (AOR) 2.0, 95% CI 1.85-2.25).
      Female cases were 40% less likely to default treatment compared to their male
      counterparts (AOR 0.6, 95% CI 0.51-0.71). Treatment default was less likely among
      cases >24 years old compared to younger cases (25-34 years: AOR 0.8, 95% CI 0.77
      0.87; 35-44 years: AOR 0.6, 95% CI 0.50-0.64; 45-54 years: AOR 0.4, 95% CI 0.32
      0.49; 55-64 years: AOR 0.3, 95% CI 0.21-0.43; >64 years: AOR 0.3, 95% CI 0.19
      0.35). Co-infected cases receiving antiretroviral therapy (ART) were 40% less
      likely to default TB treatment relative to those whose ART status was unknown
      (AOR 0.6, 95% CI 0.46-0.57). CONCLUSIONS: Salient factors influence TB patient
      treatment default in the Free State Province. Therefore, the strengthening of
      clinical and programmatic interventions for patients at high risk of treatment
      default is recommended. In particular, ART provision to co-infected cases
      facilitates TB treatment adherence and outcomes.

PMID- 27894980
TI  - Natural killer cells in inflammatory heart disease.
AB  - Despite of a multitude of excellent studies, the regulatory role of natural
      killer (NK) cells in the pathogenesis of inflammatory cardiac disease is greatly
      underappreciated. Clinical abnormalities in the numbers and functions of NK cells
      are observed in myocarditis and inflammatory dilated cardiomyopathy (DCMi) as
      well as in cardiac transplant rejection [1-6]. Because treatment of these
      disorders remains largely symptomatic in nature, patients have little options for
      targeted therapies [7,8]. However, blockade of NK cells and their receptors can
      protect against inflammation and damage in animal models of cardiac injury and
      inflammation. In these models, NK cells suppress the maturation and trafficking
      of inflammatory cells, alter the local cytokine and chemokine environments, and
      induce apoptosis in nearby resident and hematopoietic cells [1,9,10]. This review
      will dissect each protective mechanism employed by NK cells and explore how their
      properties might be exploited for their therapeutic potential.

PMID- 27894986
TI  - Application of molecular genotyping to determine prevalence of HPV strains in Pap
      smears of Kazakhstan women.
AB  - OBJECTIVES: Human papillomavirus is the main causative agent for cervical cancer.
      However, few data are available about HPV prevalence in Kazakhstan. The aims of
      this study were to genotype HPV DNA in Pap smear samples of women to determine
      prevalence of carcinogenic HPV types in Astana, Kazakhstan and to analyze the
      association between HPV positivity and the cytology results of patient samples.
      METHODS: Pap smear materials were obtained from 140 patients aged 18-59, who
      visited the outpatient gynecological clinic. Microscopic examination was done to
      detect dysplasia, and HPV genotyping was done using real-time multiplex PCR.
      RESULTS: HPV testing showed that among 61 HPV positive patients, the most
      prevalent types were 16 and 18. Microscopic examination showed that 79% of the
      samples had normal cytology, while 13% had CIN grade I, 5% had CIN grade II, and
      3% had CIN grade III. The analysis revealed that 12% of the samples had CIN
      cytology and presence of HPV. Approximately 31% had HPV without cervical
      dysplasia, while 8% of samples were CIN positive without HPV infection. A
      statistically significant relationship between HPV 16 and HPV 33 positive samples
      and CIN grade II and III was found. CONCLUSIONS: Overall, this study will help to
      strengthen and guide health policy implementation of primary and secondary
      cervical cancer prevention strategies in Kazakhstan.

PMID- 27894987
TI  - A novel approach for dry powder coating of pellets with Ethylcellulose. Part I:
      Evaluation of film formulation and process set up.
AB  - An innovative dry powder coating technology was developed in a high-shear
      granulator using ethylcellulose (E10) as polymer. Several solid plasticizers were
      investigated with the aim of decreasing the polymer Tg at least to the highest
      possible working temperature (80 degrees C). DSC analysis of physical mixtures of
      E10 and plasticizers evidenced that lauric acid (LA) was the most effective
      plasticizer. In order to reach the target temperature a liquid plasticizer, oleic
      acid (OA), was introduced in the coating formulation. Free films were then
      prepared and the target minimum film forming temperature (MFFT) was established
      in the range 70-80 degrees C. Depending on the LA:OA weight ratio, Kollidon VA64
      was included to decrease the LA recrystallization, while talc served as anti
      sticking agent. Curing at the MFFT ensured the formation of homogeneous and
      stable films with good stability on storage. The dry powder coating process of
      placebo pellets was then developed, consisting of a combination of liquid
      assisted and thermal adhesion methods. The best coating formulations in terms of
      yields, coating efficiency (expressed as Relative Standard Deviation of the
      weight applied) and low pellets aggregation were based on E10:LA:OA in a weight
      ratio of 65:20:15 and 60:20:20. Moreover pellets remained stable after 1year of
      storage (25 degrees C/60% R.H.).

PMID- 27894988
TI  - Experimental observations and dissipative particle dynamic simulations on
      microstructures of pH-sensitive polymer containing amorphous solid dispersions.
AB  - Amorphous solid dispersion (ASD) technique is an effective strategy to increase
      the dissolution rate of poorly soluble drugs. However, it is inherently unstable,
      and the molecular basis for achieving kinetic stability is not well understood.
      In this study, lacidipine-Eudragit_E_100 solid dispersions with 20% drug loading
      were prepared using the solvent evaporation. Dissolution tested showed that ASD
      had a significantly high rate, which was dependent on the pH of the medium. Based
      on time-dependent measurement of supersaturation and particle size, inhibition of
      crystal growth by Eudragit_E_100 differed at pH 1.2 and 6.8 to a great extent.
      Dissipative particle dynamic (DPD) simulation revealed that at pH 1.2, the
      swollen microstructures of the particles were associated with rapid drug release.
      At pH 6.8, a compacted microstructure of small amorphous particle-aggregated
      large particles was associated with slow dissolution. The DPD simulation provides
      insight into the structural basis for experimental observations, and thus is a
      useful tool to investigate the microstructures of ASD.

PMID- 27894989
TI  - New pieces on genetic diversity and evolutionary history of hepatitis B virus:
      Characterization of the novel subgenotype F6.

PMID- 27894990
TI  - Microevolutionary analyses of Pythium insidiosum isolates of Brazil and Thailand
      based on exo-1,3-beta-glucanase gene.
AB  - Pythium insidiosum is an important oomycete due to its ability to infect humans
      and animals. It causes pythiosis, a disease of difficult treatment that occurs
      more frequently in humans in Thailand and in horses in Brazil. Since cell-wall
      components are frequently related to host shifts, we decided here to use
      sequences from the exo-1,3-beta-glucanase gene (exo1), which encodes an
      immunodominant protein putatively involved in cell wall remodeling, to
      investigate the microevolutionary relationships of Brazilian and Thai isolates of
      P. insidiosum. After neutrality ratification, the phylogenetic analyses performed
      through Maximum parsimony (MP), Neighbor-joining (NJ), Maximum likelihood (ML),
      and Bayesian analysis (BA) strongly supported Thai isolates being paraphyletic in
      relation to those from Brazil. The structure recovered by these analyses, as well
      as by Spatial Analysis of Molecular Variance (SAMOVA), suggests the subdivision
      of P. insidiosum into three clades or population groups, which are able to
      explain almost 81% of the variation encountered for exo1. Moreover, the two
      identified Thai clades were almost as strongly differentiated between each other,
      as they were from the Brazilian clade, suggesting an ancient Asian subdivision.
      The derived positioning in the phylogenetic tree, linked to the lower diversity
      values and the recent expansion signs detected for the Brazilian clade, further
      support this clade as derived in relation to the Asian populations. Thus,
      although some patterns presented here are compatible with those recovered with
      different molecular markers, exo1 was revealed to be a good marker for studying
      evolution in Pythium, providing robust and strongly supported results with regard
      to the patterns of origin and diversification of P. insidiosum.

PMID- 27894991
TI  - Bats are rare reservoirs of Staphylococcus aureus complex in Gabon.
AB  - The colonization of afro-tropical wildlife with Staphylococcus aureus and the
      derived clade Staphylococcus schweitzeri remains largely unknown. A reservoir in
      bats could be of importance since bats and humans share overlapping habitats. In
      addition, bats are food sources in some African regions and can be the cause of
      zoonotic diseases. Here, we present a cross-sectional survey employing pharyngeal
      swabs of captured and released bats (n=133) in a forest area of Gabon. We
      detected low colonization rates of S. aureus (4-6%) and S. schweitzeri (4%) in
      two out of four species of fruit bats, namely Rousettus aegyptiacus and
      Micropteropus pusillus, but not in insectivorous bats. Multilocus sequence typing
      showed that S. aureus from Gabonese bats (ST2984, ST3259, ST3301, ST3302) were
      distinct from major African human associated clones (ST15, ST121, ST152). S.
      schweitzeri from bats (ST1697, ST1700) clustered with S. schweitzeri from other
      species (bats, monkeys) from Nigeria and Cote d'Ivoire. In conclusion,
      colonization rates of bats with S. aureus and S. schweitzeri were low in our
      study. Phylogenetic analysis supports an intense geographical dispersal of S.
      schweitzeri among different mammalian wildlife hosts.

PMID- 27894992
TI  - Analysis of complete genome sequences of G9P[19] rotavirus strains from human and
      piglet with diarrhea provides evidence for whole-genome interspecies transmission
      of nonreassorted porcine rotavirus.
AB  - Whole genomes of G9P[19] human (RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19]) and
      porcine (RVA/Pig-wt/THA/CMP-015-12/2012/G9P[19]) rotaviruses concurrently
      detected in the same geographical area in northern Thailand were sequenced and
      analyzed for their genetic relationships using bioinformatic tools. The complete
      genome sequence of human rotavirus RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] was
      most closely related to those of porcine rotavirus RVA/Pig-wt/THA/CMP-015
      12/2012/G9P[19] and to those of porcine-like human and porcine rotaviruses
      reference strains than to those of human rotavirus reference strains. The
      genotype constellation of G9P[19] detected in human and piglet were identical and
      displayed as the G9-P[19]-I5-R1-C1-M1-A8-N1-T1-E1-H1 genotypes with the
      nucleotide sequence identities of VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3,
      NSP4, and NSP5 at 99.0%, 99.5%, 93.2%, 97.7%, 97.7%, 85.6%, 89.5%, 93.2%, 92.9%,
      94.0%, and 98.1%, respectively. The findings indicate that human rotavirus strain
      RVA/Human-wt/THA/CMH-S070-13/2013/G9P[19] containing the genome segments of
      porcine genetic backbone is most likely a human rotavirus of porcine origin. Our
      data provide an evidence of interspecies transmission and whole-genome
      transmission of nonreassorted G9P[19] porcine RVA to human occurring in nature in
      northern Thailand.

PMID- 27894993
TI  - New adenoviruses from new primate hosts - growing diversity reveals taxonomic
      weak points.
AB  - The knowledge of the closest human relatives of human adenoviruses (AdVs) such as
      adenoviruses found in nonhuman primates is still limited, despite the growing
      importance of adenoviruses in vaccine development, gene and cancer therapy. We
      examined 153 stool samples of 17 non-human primate species and detected
      adenoviral DNA sequences of DNA polymerase (DPOL) gene in 54 samples (35%),
      originating from 12 out of 17 primate species. We further sequenced 15 hexon gene
      fragments and based on the phylogenetic analysis we propose two new provisional
      species SAdV-H and SAdV-I. Our study shows extensive diversity of adenoviral
      strains forming separate clades often from closely related host species from old
      world monkeys suggesting the existence of new species of AdVs and shows the
      necessity for clear ICTV guidelines for final establishment of so far provisional
      AdV species.

PMID- 27894994
TI  - A new genus of Anostomidae (Ostariophysi: Characiformes): Diversity, phylogeny
      and biogeography based on cytogenetic, molecular and morphological data.
AB  - A new genus of Anostomidae (Characiformes) is described to include ten valid
      extant species previously classified in Leporinus or Hypomasticus and distributed
      throughout most major river basins in South America: L. brinco, L. conirostris,
      L. elongatus, H. garmani, L. macrocephalus, L. muyscorum, L. obtusidens, L.
      piavussu, L. reinhardti, and L. trifasciatus. The monophyly of Megaleporinus is
      well-supported in a phylogenetic analysis based on two mitochondrial and three
      nuclear genes, as well as its sister group relationship to Abramites.
      Megaleporinus is diagnosed by having the exclusive combination of three unicuspid
      teeth on each premaxillary and dentary bone and a color pattern composed of one
      to four dark midlateral blotches. Additional distinguishing features and possible
      synapomorphies include a unique ZZ/ZW sex chromosome system confirmed for six
      congeners and a drumming apparatus wherein the first rib is elongated and
      associated with hypertrophied intercostal muscles, which was confirmed for three
      congeners as exclusive to mature males. Furthermore, our study identified at
      least four undescribed cryptic species, emphasizing the need for further
      taxonomic work and genetic analyses. A time-calibrated phylogenetic and
      biogeographical analysis of the new genus suggests that speciation in the proto
      Amazon-Orinoco lineage was primarily driven by paleogeographic processes, such as
      the formation of the Orinoco and Tocantins basins. Dispersal and diversification
      of the genus in coastal basins draining the Eastern Brazilian Shield appears to
      have been facilitated by connections between paleo-basins during low sea level
      periods and headwater captures between coastal and inland watersheds. The present
      contribution demonstrates the importance of integrating data from morphology, DNA
      sequences and cytogenetics to advance the taxonomy and systematics of any complex
      species group.

PMID- 27894995
TI  - Short branches lead to systematic artifacts when BLAST searches are used as
      surrogate for phylogenetic reconstruction.
AB  - Long Branch Attraction (LBA) is a well-known artifact in phylogenetic
      reconstruction when dealing with branch length heterogeneity. Here we show
      another phenomenon, Short Branch Attraction (SBA), which occurs when BLAST
      searches, a phenetic analysis, are used as a surrogate method for phylogenetic
      analysis. This error also results from branch length heterogeneity, but this time
      it is the short branches that are attracting. The SBA artifact is reciprocal and
      can be returned 100% of the time when multiple branches differ in length by a
      factor of more than two. SBA is an intended feature of BLAST searches, but
      becomes an issue, when top scoring BLAST hit analyses are used to infer
      Horizontal Gene Transfers (HGTs), assign taxonomic category with environmental
      sequence data in phylotyping, or gather homologous sequences for building gene
      families. SBA can lead researchers to believe that there has been a HGT event
      when only vertical descent has occurred, cause slowly evolving taxa to be over
      represented and quickly evolving taxa to be under-represented in phylotyping, or
      systematically exclude quickly evolving taxa from analyses. SBA also contributes
      to the changing results of top scoring BLAST hit analyses as the database grows,
      because more slowly evolving taxa, or short branches, are added over time,
      introducing more potential for SBA. SBA can be detected by examining reciprocal
      best BLAST hits among a larger group of taxa, including the known closest
      phylogenetic neighbors. Therefore, one should look for this phenomenon when
      conducting best BLAST hit analyses as a surrogate method to identify HGTs, in
      phylotyping, or when using BLAST to gather homologous sequences.

PMID- 27894996
TI  - Are ocean currents too slow to counteract SAR11 evolution? A next-generation
      sequencing, phylogeographic analysis.
AB  - This work set out to shed light on the phylogeography of the SAR11 clade of
      Alphaproteobacteria, which is probably the most abundant group of heterotrophic
      bacteria on Earth. In particular, we assessed the degree to which empirical
      evidence (environmental DNA sequences) supports the concept that SAR11 lineages
      evolve faster than they are dispersed thus generating vicariant distributions, as
      predicted by recent simulation efforts. We generated 16S rRNA gene sequences from
      surface seawater collected at the South West Atlantic Ocean and combined these
      data with previously published sequences from similar environments from
      elsewhere. Altogether, these data consisted in about 1e6 reads, from which we
      generated 355,306 high quality sequences of which 95,318 corresponded to SAR11.
      Quantitative phylogeographic analyses supported the existence of a spatially
      explicit distribution of SAR11 species and provided evidence in favor of the idea
      that dispersal limitations significantly contribute to SAR11 radiation throughout
      the world's oceans. Likewise, pairwise phylogenetic distances between the
      communities studied here were significantly correlated with the genetic
      divergences predicted by a previously proposed neutral model. As discussed in the
      paper, these findings are compatible with the concept that the ocean surface
      constitutes a homogeneous environment for SAR11, in agreement with previous
      experimental data. We discuss the implications of this hypothesis in a global
      change scenario. This is the first study combining high throughput sequencing and
      phylogenic analysis to study bacterial phylogeography and reporting a distance
      decay pattern of phylogenetic distances for bacteria.

PMID- 27894997
TI  - Structural and evolutionary analyses reveal determinants of DNA binding
      specificities of nucleoid-associated proteins HU and IHF.
AB  - Nucleoid-associated proteins (NAPs) are chromosome-organizing factors, which
      affect the transcriptional landscape of a bacterial cell. HU is an NAP, which
      binds to DNA with a broad specificity while homologous IHF (Integration Host
      Factor), binds DNA with moderately higher specificity. Specificity and
      differential binding affinity of HU/IHF proteins towards their target binding
      sites play a crucial role in their regulatory dynamics. Decades of biochemical
      and genomic studies have been carried out for HU and IHF like proteins. Yet,
      questions related to their DNA binding specificity, and differential ability to
      bend DNA thus affecting the binding site length remained unanswered. In addition,
      the problem has not been investigated from an evolutionary perspective. Our
      phylogenetic analysis revealed three major clades belonging to HU, IHFalpha and
      IHFbeta like proteins with reference to E. coli. We carried out a comparative
      analysis of three-dimensional structures of HU/IHF proteins to gain insight into
      the structural basis of clade division. The present study revealed three major
      features which contribute to differential DNA binding specificity of HU/IHF
      proteins, (I) conformational restriction of DNA binding residues due to salt
      bridge formation, (II) the enrichment of alanine in the DNA binding site
      increasing conformational space of flexible side chains in its vicinity and (III)
      nature of DNA binding residue (Arg to Lys bias in different clades) which
      interacts differentially to DNA bases. We observed an extended electropositive
      surface at the DNA draping site for IHF clade proteins compared to HU, which
      stabilizes the DNA bend. Differences in the dimer stabilization strategies
      between HU and IHF were also observed. Our analysis reveals a comprehensive
      evolutionary picture, which rationalizes the origin of multi-specificity of
      HU/IHF proteins using sequence and structure-based determinants, which could also
      be applied to understand differences in binding specificities of other nucleic
      acid binding proteins.

PMID- 27894999
TI  - Matched-Comparative Modeling of Normal and Diseased Human Airway Responses Using
      a Microengineered Breathing Lung Chip.
AB  - Smoking represents a major risk factor for chronic obstructive pulmonary disease
      (COPD), but it is difficult to characterize smoke-induced injury responses under
      physiological breathing conditions in humans due to patient-to-patient
      variability. Here, we show that a small airway-on-a-chip device lined by living
      human bronchiolar epithelium from normal or COPD patients can be connected to an
      instrument that "breathes" whole cigarette smoke in and out of the chips to study
      smoke-induced pathophysiology in vitro. This technology enables true matched
      comparisons of biological responses by culturing cells from the same individual
      with or without smoke exposure. These studies led to identification of ciliary
      micropathologies, COPD-specific molecular signatures, and epithelial responses to
      smoke generated by electronic cigarettes. The smoking airway-on-a-chip represents
      a tool to study normal and disease-specific responses of the human lung to
      inhaled smoke across molecular, cellular and tissue-level responses in an organ
      relevant context.

PMID- 27894998
TI  - Push-Pull and Feedback Mechanisms Can Align Signaling System Outputs with Inputs.
AB  - Many cell signaling systems, including the yeast pheromone response system,
      exhibit "dose-response alignment" (DoRA), in which output of one or more
      downstream steps closely matches the fraction of occupied receptors. DoRA can
      improve the fidelity of transmitted dose information. Here, we searched
      systematically for biochemical network topologies that produced DoRA. Most
      networks, including many containing feedback and feedforward loops, could not
      produce DoRA. However, networks including "push-pull" mechanisms, in which the
      active form of a signaling species stimulates downstream activity and the
      nominally inactive form reduces downstream activity, enabled perfect DoRA.
      Networks containing feedbacks enabled DoRA, but only if they also compared
      feedback to input and adjusted output to match. Our results establish push-pull
      as a non-feedback mechanism to align output with variable input and maximize
      information transfer in signaling systems. They also suggest genetic approaches
      to determine whether particular signaling systems use feedback or push-pull
      control.

PMID- 27895000
TI  - Severe Acute Otitis Media and Acute Mastoiditis in Adults.
AB  - OBJECTIVE: To evaluate and compare clinical and microbiological findings in
      adults hospitalized for acute otitis media (AOM) or mastoid infections (acute or
      latent). MATERIALS AND METHODS: We retrospectively reviewed the medical records
      of all adults (>=17 years old) hospitalized (between 2003 and 2012) at a tertiary
      referral center for acute mastoid infections or AOM not responding to outpatient
      medical treatment. RESULTS: Of the 160 patients in the study sample, 19% had an
      infection caused by S. pyogenes, 14% by S. pneumoniae, and 11% by P. aeruginosa.
      AOM was the most common infection (38%), whereas 33% had acute mastoiditis (AM),
      18% had latent mastoiditis (LM), and 13% AM of a chronically infected ear (AMc).
      In contrast to the other infections, P. aeruginosa (30%) and S. aureus (25%) were
      most common in AMc. Otorrhea (83%), tympanic membrane perforation (57%), and
      hearing problems (83%) were common in S. pyogenes infections. Patients with S.
      pneumoniae had longer lengths of hospitalization than those with other bacterial
      infections (7 vs. 4 days). Otorrhea (94%) and retroauricular symptoms were more
      common in P. aeruginosa infections. Hearing symptoms were common (67%) but fever
      (32%) and retroauricular symptoms were uncommon in AOM. Fever (44%) and mastoid
      tenderness (65%) were common in AM. Patients with LM underwent the most
      mastoidectomies (54%). Prior medical conditions, retroauricular symptoms,
      otorrhea (90%), and post-infection problems were common in AMc. CONCLUSION: The
      bacteriological etiology of hospitalized AOM more closely resembled those of LM
      and AM than that of AMc. Adults hospitalized for AOM or AM required fewer
      mastoidectomies than those hospitalized for LM or AMc.

PMID- 27895002
TI  - Impression Material in the External and Middle Ear: an Overview of the Literature
      and a Stepwise Approach for Removal.
AB  - Here, we provide a literature overview of cases with protruding molding material
      for earplugs or hearing aids and subsequent required treatment, including our own
      cases. Patients at risk are those with impaired tympanic membranes or who
      previously underwent otologic surgery. Symptoms such as otalgia, tinnitus, and
      vertigo are alarming but do not always arise. In case of doubt, a CT scan is of
      additive value to prepare for adequate surgical removal and to limit potential
      damage. A stepwise approach for the clinician on how to address these challenging
      cases is presented, based upon the literature and our own experience.

PMID- 27895004
TI  - Predictors of Vascular Cognitive Impairment Poststroke in a Middle Eastern
      (Bahrain) Cohort: A Proposed Case-Control Comparison.
AB  - BACKGROUND: Poststroke dementia and cognitive impairment are associated with poor
      long-term outcomes after stroke. The contribution of genetic factors such as the
      presence of apolipoprotein (ApoE) E4 allele and its association with cognitive
      impairment poststroke remains inconclusive, particularly in Middle Eastern
      regions. OBJECTIVE: The aim of this study is to examine all correlates and
      potential predictors of cognitive impairment including self-awareness and
      regulation deficits in stroke patients and compare these functions with healthy
      older adults from a Middle Eastern population. METHODS: A prospective stroke
      sample of 200 patients (case group) and 100 healthy aging individuals (control
      group) will be recruited from the largest medical complex in Bahrain. A
      neuropsychological battery of cognitive assessments (global, executive, and
      metacognition) will be conducted on all participants. Participants will be
      categorized into 4 subgroups (nonvascular cognitive impairment, vascular
      cognitive impairment with no dementia, vascular dementia, and mixed dementia)
      using standardized cognitive assessment scores and the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, dementia criteria. Biomarkers will
      include ApoE genotype, soluble form of receptor for advanced glycation end
      products, neprilysin, beta-secretase 1, biochemistry, and hematology
      measurements. RESULTS: The primary study outcome is to determine early risk
      factors for cognitive impairment after stroke in a Bahraini cohort. The study has
      received full ethical approval from the Bahrain Ministry of Health and from the
      affiliated university. CONCLUSIONS: With increasing stroke incidence rates in the
      Middle East, this research study will provide useful biological and
      epidemiological data for future development and planning of health policies and
      guidelines for stroke care within the Gulf region.

PMID- 27895003
TI  - Effect on Nitrogen Balance, Thermogenesis, Body Composition, Satiety, and
      Circulating Branched Chain Amino Acid Levels up to One Year after Surgery:
      Protocol of a Randomized Controlled Trial on Dietary Protein During Surgical
      Weight Loss.
AB  - BACKGROUND: Bariatric surgery (BS), the most effective treatment for severe
      obesity, typically results in 40-50 kg weight loss in the year following the
      surgery. Beyond its action on protein metabolism, dietary protein intake (PI)
      affects satiety, thermogenesis, energy efficiency, and body composition (BC).
      However, the required amount of PI after surgical weight loss is not known. The
      current daily PI recommendation for diet-induced weight loss is 0.8 g/kg ideal
      body weight (IBW) per day, but whether this amount is sufficient to preserve fat
      free mass during active surgical weight loss is unknown. OBJECTIVE: To evaluate
      the effect of a 3-month dietary protein supplementation (PS) on nitrogen balance
      (NB), BC, energy expenditure, and satiety in women undergoing either gastric
      bypass or vertical sleeve gastrectomy. METHODS: In this randomized prospective
      study, participants will be randomized to a high protein supplementation group
      (1.2 g/kg IBW per day) or standard protein supplementation group (0.8 g/kg IBW
      per day) based on current guidelines. Outcome measures including NB, BC,
      circulating branched chain amino acids, and satiety, which will be assessed
      presurgery, and at 3-months and 12-months postsurgery. RESULTS: To date, no
      studies have examined the effect of dietary PS after BS. Current guidelines for
      PI after surgery are based on weak evidence. CONCLUSIONS: The results of this
      study will contribute to the development of evidence-based data regarding the
      safe and optimal dietary PI and supplementation after BS. TRIAL REGISTRATION:
      Clinicaltrials.gov NCT02269410; http://clinicaltrials.gov/ct2/show/NCT02269410
      (Archived by WebCite at http://www.webcitation.org/6m2f2QLeg).

PMID- 27895007
TI  - Needling depth at BL52 in 13 cadavers.

PMID- 27895005
TI  - Qualitative Analysis of Cognitive Interviews With School Children: A Web-Based
      Food Intake Questionnaire.
AB  - BACKGROUND: The use of computers to administer dietary assessment questionnaires
      has shown potential, particularly due to the variety of interactive features that
      can attract and sustain children's attention. Cognitive interviews can help
      researchers to gain insights into how children understand and elaborate their
      response processes in this type of questionnaire. OBJECTIVE: To present the
      cognitive interview results of children who answered the WebCAAFE, a Web-based
      questionnaire, to obtain an in-depth understanding of children's response
      processes. METHODS: Cognitive interviews were conducted with children (using a
      pretested interview script). Analyses were carried out using thematic analysis
      within a grounded theory framework of inductive coding. RESULTS: A total of 40
      children participated in the study, and 4 themes were identified: (1) the meaning
      of words, (2) understanding instructions, (3) ways to resolve possible problems,
      and (4) suggestions for improving the questionnaire. Most children understood
      questions that assessed nutritional intake over the past 24 hours, although the
      structure of the questionnaire designed to facilitate recall of dietary intake
      was not always fully understood. Younger children (7 and 8 years old) had more
      difficulty relating the food images to mixed dishes and foods eaten with bread
      (eg, jam, cheese). Children were able to provide suggestions for improving future
      versions of the questionnaire. CONCLUSIONS: More attention should be paid to
      children aged 8 years or below, as they had the greatest difficulty completing
      the WebCAAFE.

PMID- 27895006
TI  - Patients' Need for Tailored Comparative Health Care Information: A Qualitative
      Study on Choosing a Hospital.
AB  - BACKGROUND: The Internet is increasingly being used to provide patients with
      information about the quality of care of different health care providers.
      Although online comparative health care information is widely available
      internationally, and patients have been shown to be interested in this
      information, its effect on patients' decision making is still limited. OBJECTIVE:
      This study aimed to explore patients' preferences regarding information
      presentation and their values concerning tailored comparative health care
      information. Meeting patients' information presentation needs might increase the
      perceived relevance and use of the information. METHODS: A total of 38 people
      participated in 4 focus groups. Comparative health care information about hip and
      knee replacement surgery was used as a case example. One part of the interview
      focused on patients' information presentation preferences, whereas the other part
      focused on patients' values of tailored information (ie, showing reviews of
      patients with comparable demographics). The qualitative data were transcribed
      verbatim and analyzed using the constant comparative method. RESULTS: The
      following themes were deduced from the transcripts: number of health care
      providers to be presented, order in which providers are presented, relevancy of
      tailoring patient reviews, and concerns about tailoring. Participants'
      preferences differed concerning how many and in which order health care providers
      must be presented. Most participants had no interest in patient reviews that were
      shown for specific subgroups based on age, gender, or ethnicity. Concerns of
      tailoring were related to the representativeness of results and the complexity of
      information. A need for information about the medical specialist when choosing a
      hospital was stressed by several participants. CONCLUSIONS: The preferences for
      how comparative health care information should be presented differ between
      people. "Information on demand" and information about the medical specialist
      might be promising ways to increase the relevancy and use of online comparative
      health care information. Future research should focus on how different groups of
      people use comparative health care information for different health care choices
      in real life.

PMID- 27895009
TI  - IncP Plasmid Carrying Colistin Resistance Gene mcr-1 in Klebsiella pneumoniae
      from Hospital Sewage.
AB  - A Klebsiella pneumoniae strain of sequence type 313 (ST313) recovered from
      hospital sewage was found carrying the plasmid-borne colistin resistance gene mcr
      1, which was bracketed by two copies of the insertion sequence ISApl1 on a 57-kb
      self-transmissible IncP-type plasmid of a new IncP-1 clade. The carriage of mcr-1
      on a self-transmissible broad-host-range plasmid highlights that mcr-1 has the
      potential to spread beyond the Enterobacteriaceae family.

PMID- 27895008
TI  - De Novo Emergence of Genetically Resistant Mutants of Mycobacterium tuberculosis
      from the Persistence Phase Cells Formed against Antituberculosis Drugs In Vitro.
AB  - Bacterial persisters are a subpopulation of cells that can tolerate lethal
      concentrations of antibiotics. However, the possibility of the emergence of
      genetically resistant mutants from antibiotic persister cell populations, upon
      continued exposure to lethal concentrations of antibiotics, remained unexplored.
      In the present study, we found that Mycobacterium tuberculosis cells exposed
      continuously to lethal concentrations of rifampin (RIF) or moxifloxacin (MXF) for
      prolonged durations showed killing, RIF/MXF persistence, and regrowth phases. RIF
      resistant or MXF-resistant mutants carrying clinically relevant mutations in the
      rpoB or gyrA gene, respectively, were found to emerge at high frequency from the
      RIF persistence phase population. A Luria-Delbruck fluctuation experiment using
      RIF-exposed M. tuberculosis cells showed that the rpoB mutants were not
      preexistent in the population but were formed de novo from the RIF persistence
      phase population. The RIF persistence phase M. tuberculosis cells carried
      elevated levels of hydroxyl radical that inflicted extensive genome-wide
      mutations, generating RIF-resistant mutants. Consistent with the elevated levels
      of hydroxyl radical-mediated genome-wide random mutagenesis, MXF-resistant M.
      tuberculosis gyrA de novo mutants could be selected from the RIF persistence
      phase cells. Thus, unlike previous studies, which showed emergence of genetically
      resistant mutants upon exposure of bacteria for short durations to sublethal
      concentrations of antibiotics, our study demonstrates that continuous prolonged
      exposure of M. tuberculosis cells to lethal concentrations of an antibiotic
      generates antibiotic persistence phase cells that form a reservoir for the
      generation of genetically resistant mutants to the same antibiotic or another
      antibiotic. These findings may have clinical significance in the emergence of
      drug-resistant tubercle bacilli.

PMID- 27895010
TI  - Mutations Associated with Decreased Susceptibility to Seven Antimicrobial
      Families in Field and Laboratory-Derived Mycoplasma bovis Strains.
AB  - The molecular mechanisms of resistance to fluoroquinolones, tetracyclines, an
      aminocyclitol, macrolides, a lincosamide, a phenicol, and pleuromutilins were
      investigated in Mycoplasma bovis For the identification of mutations responsible
      for the high MICs of certain antibiotics, whole-genome sequencing of 35 M. bovis
      field isolates and 36 laboratory-derived antibiotic-resistant mutants was
      performed. In vitro resistant mutants were selected by serial passages of M.
      bovis in broth medium containing subinhibitory concentrations of the antibiotics.
      Mutations associated with high fluoroquinolones MICs were found at positions 244
      to 260 and at positions 232 to 250 (according to Escherichia coli numbering) of
      the quinolone resistance-determining regions of the gyrA and parC genes,
      respectively. Alterations related to elevated tetracycline MICs were described at
      positions 962 to 967, 1058, 1195, 1196, and 1199 of genes encoding the 16S rRNA
      and forming the primary tetracycline binding site. Single transversion at
      position 1192 of the rrs1 gene resulted in a spectinomycin MIC of 256 MUg/ml.
      Mutations responsible for high macrolide, lincomycin, florfenicol, and
      pleuromutilin antibiotic MICs were identified in genes encoding 23S rRNA.
      Understanding antibiotic resistance mechanisms is an important tool for future
      developments of genetic-based diagnostic assays for the rapid detection of
      resistant M. bovis strains.

PMID- 27895011
TI  - Using In Vitro Dynamic Models To Evaluate Fluoroquinolone Activity against
      Emergence of Resistant Salmonella enterica Serovar Typhimurium.
AB  - The objectives of this study were to determine pharmacokinetic/pharmacodynamic
      (PK/PD) indices of fluoroquinolones that minimize the emergence of resistant
      Salmonella enterica serovar Typhimurium (S Typhimurium) using in vitro dynamic
      models and to establish mechanisms of resistance. Three fluoroquinolones,
      difloxacin (DIF), enrofloxacin (ENR), and marbofloxacin (MAR), at five dose
      levels and 3 days of treatment were simulated. Bacterial killing-regrowth
      kinetics and emergence of resistant bacteria after antibacterial drug exposure
      were quantified. PK/PD indices associated with different levels of antibacterial
      activity were computed. Mechanisms of fluoroquinolone resistance were determined
      by analyzing target mutations in the quinolone resistance-determining regions
      (QRDRs) and by analyzing overexpression of efflux pumps. Maximum losses in
      susceptibility of fluoroquinolone-exposed S Typhimurium occurred at a simulated
      AUC/MIC ratio (area under the concentration-time curve over 24 h in the steady
      state divided by the MIC) of 47 to 71. Target mutations in gyrA (S83F) and
      overexpression of acrAB-tolC contributed to decreased susceptibility in
      fluoroquinolone-exposed S Typhimurium. The current data suggest AUC/MIC
      (AUC/mutant prevention concentration [MPC])-dependent selection of resistant
      mutants of S Typhimurium, with AUC/MPC ratios of 69 (DIF), 62 (ENR), and 39 (MAR)
      being protective against selection of resistant mutants. These values could not
      be achieved in veterinary clinical areas under the current recommended
      therapeutic doses of the fluoroquinolones, suggesting the need to reassess the
      current dosing regimen to include both clinical efficacy and minimization of
      emergence of resistant bacteria.

PMID- 27895012
TI  - Multicenter Observational Study of Ceftaroline Fosamil for Methicillin-Resistant
      Staphylococcus aureus Bloodstream Infections.
AB  - Novel therapies for methicillin-resistant Staphylococcus aureus (MRSA)
      bloodstream infection (BSI) are needed in the setting of reduced antibiotic
      susceptibilities and therapeutic failure. Ceftaroline is a cephalosporin
      antibiotic with MRSA activity. Although not FDA approved for MRSA BSI,
      ceftaroline has generated much interest as a potential treatment option. However,
      detailed descriptions of its use in this setting remain limited. To address this,
      we conducted a retrospective, multicenter, observational study of adult patients
      with MRSA BSI treated with at least 72 h of ceftaroline from 2011 to 2015. Safety
      outcomes were examined in the overall cohort, while efficacy outcomes were
      examined among patients who had not cleared their BSI prior to ceftaroline
      initiation. Data were also stratified by ceftaroline monotherapy or combination
      therapy. Predictors of clinical failure on ceftaroline treatment were also
      sought. Overall, 211 patients were included in the safety population; Clostridium
      difficile infection, rash, and neutropenia occurred in 6 patients (2.8%), 7
      patients (3.3%), and 3 patients (1.4%), respectively. Clinical success was
      observed in 86 (68.3%) of the 126 patients included in the efficacy population.
      The monotherapy and combination therapy subgroups had similar proportions of
      patients experiencing success (69.7 and 64.9%, respectively). The median BSI
      durations post-ceftaroline treatment were 2 days (interquartile range, 1 to 4
      days) for monotherapy and 3 days (interquartile range, 1.5 to 5 days) for
      combination therapy. Higher acute physiology and chronic health evaluation II
      scores and comorbid malignancy independently predicted treatment failure.
      Ceftaroline appears effective for MRSA BSI as both monotherapy and combination
      therapy. However, comparative studies are needed to further delineate the role of
      ceftaroline in MRSA BSI treatment.

PMID- 27895013
TI  - Frequent Cross-Resistance to Dapivirine in HIV-1 Subtype C-Infected Individuals
      after First-Line Antiretroviral Therapy Failure in South Africa.
AB  - A vaginal ring containing dapivirine (DPV) has shown moderate protective efficacy
      against HIV-1 acquisition, but the activity of DPV against efavirenz (EFV)- and
      nevirapine (NVP)-resistant viruses that could be transmitted is not well defined.
      We investigated DPV cross-resistance of subtype C HIV-1 from individuals on
      failing NVP- or EFV-containing antiretroviral therapy (ART) in South Africa.
      Plasma samples were obtained from individuals with >10,000 copies of HIV RNA/ml
      and with HIV-1 containing at least one non-nucleoside reverse transcriptase
      (NNRTI) mutation. Susceptibility to NVP, EFV, and DPV in TZM-bl cells was
      determined for recombinant HIV-1LAI containing bulk-amplified, plasma-derived,
      full-length reverse transcriptase sequences. Fold change (FC) values were
      calculated compared with a composite 50% inhibitory concentration (IC50) from 12
      recombinant subtype C HIV-1LAI plasma-derived viruses from treatment-naive
      individuals in South Africa. A total of 25/100 (25%) samples showed >500-FCs to
      DPV compared to treatment-naive samples with IC50s exceeding the maximum DPV
      concentration tested (132 ng/ml). A total of 66/100 (66%) samples displayed 3- to
      306-FCs, with a median IC50 of 17.6 ng/ml. Only 9/100 (9%) samples were
      susceptible to DPV (FC < 3). Mutations L100I and K103N were significantly more
      frequent in samples with >500-fold resistance to DPV compared to samples with a
      <=500-fold resistance. A total of 91% of samples with NNRTI-resistant HIV-1 from
      individuals on failing first-line ART in South Africa exhibited >=3-fold cross
      resistance to DPV. This level of resistance exceeds expected plasma
      concentrations, but very high genital tract DPV concentrations from DPV ring use
      could block viral replication. It is critically important to assess the frequency
      of transmitted and selected DPV resistance in individuals using the DPV ring.

PMID- 27895014
TI  - Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem
      Resistant Organisms.
AB  - Ceftazidime-avibactam (CAZ-AVI) is a recently approved beta-lactam-beta-lactamase
      inhibitor combination with the potential to treat serious infections caused by
      carbapenem-resistant organisms. Few patients with such infections were included
      in the CAZ-AVI clinical trials, and clinical experience is lacking. We present a
      case series of patients with infections caused by carbapenem-resistant
      Enterobacteriaceae (CRE) or Pseudomonas aeruginosa (CRPa) who were treated with
      CAZ-AVI salvage therapy on a compassionate-use basis. Physicians who had
      prescribed CAZ-AVI completed a case report form. We used descriptive statistics
      to summarize patient characteristics and treatment outcomes. We used the Wilcoxon
      rank sum test and Fisher's exact test to compare patients by treatment outcome.
      The sample included 36 patients infected with CRE and two with CRPa. The most
      common infections were intra-abdominal. Physicians categorized 60.5% of patients
      as having life-threatening infections. All but two patients received other
      antibiotics before CAZ-AVI, for a median of 13 days. The median duration of CAZ
      AVI treatment was 16 days. Twenty-five patients (65.8%) concurrently received
      other antibiotics to which their pathogen was nonresistant in vitro Twenty-eight
      patients (73.7%, 95% confidence interval [CI], 56.9 to 86.6%) experienced
      clinical and/or microbiological cure. Five patients (20.8%) with documented
      microbiological cure died, whereas 10 patients (71.4%) with no documented
      microbiological cure died (P = 0.01). In three-quarters of cases, CAZ-AVI (alone
      or combined with other antibiotics) cured infections caused by carbapenem
      resistant organisms, 95% of which had failed previous therapy. Microbiological
      cure was associated with improved survival. CAZ-AVI shows promising clinical
      results for infections for which treatment options are limited.

PMID- 27895015
TI  - Protective Effects of Human and Mouse Soluble Scavenger-Like CD6 Lymphocyte
      Receptor in a Lethal Model of Polymicrobial Sepsis.
AB  - Sepsis still constitutes an unmet clinical need, which could benefit from novel
      adjunctive strategies to conventional antibiotic therapy. The soluble form of the
      scavenger-like human CD6 lymphocyte receptor (shCD6) binds to key pathogenic
      components from Gram-positive and -negative bacteria and shows time- and dose
      dependent efficacy in mouse models of monobacterial sepsis. The objective of the
      present work was to demonstrate the effectiveness of infusing mouse and human
      sCD6 by different systemic routes, either alone or as adjunctive therapy to gold
      standard antibiotics, in a lethal model of polymicrobial sepsis. To this end,
      C57BL/6 mice undergoing high-grade septic shock induced by cecal ligation and
      puncture (CLP; >=90% lethality) were infused via the intraperitoneal (i.p.) or
      intravenous (i.v.) route with shCD6 at different doses and time points, either
      alone or in combination with imipenem/cilastatin (I/C) at a dose of 33 mg/kg of
      body weight every 8 h. Significantly reduced mortality and proinflammatory
      cytokine levels were observed by i.p. infusion of a single shCD6 dose (1.25
      mg/kg) 1 h pre- or post-CLP. When using the i.v. route, mice survival was
      significantly extended by starting shCD6 infusion at later time points post-CLP
      (up to 6 h after CLP). Significant adjunctive effects on mouse survival were
      observed by i.p. or i.v. infusion of shCD6 in combination with i.p. I/C post-CLP.
      Similar results were obtained in mice expressing high sustained levels (5 to 10
      MUg/ml) of mouse sCD6 in serum by means of transduction with hepatotropic adeno
      associated virus (AAV). Taken together, the data support the conserved
      antibacterial effects of human and mouse sCD6 and their use as adjunctive therapy
      in experimental models of complex and severe polymicrobial sepsis.

PMID- 27895016
TI  - Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of
      Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of
      Mother-to-Child HIV-1 Transmission during Breastfeeding.
AB  - The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)
      ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis
      administered to breastfed infants whose HIV-infected mothers were not on
      antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC
      pharmacokinetics to evaluate the percentage of infants with therapeutic plasma
      concentrations and to discuss these data in the context of a prophylactic
      treatment. Infants from the South African trial site underwent blood sampling for
      pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian
      approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of
      previously published pharmacokinetic models for HIV-infected children. We
      analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92
      infants, respectively. A total of 30 LPV and 20 3TC observations were considered
      missing doses and discarded from the Bayesian analysis. The overall population
      analysis showed that 30 to 40% of the infants did not reach therapeutic targets,
      regardless of treatment group. The median LPV trough concentrations at weeks 6,
      26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter),
      5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3
      mg/liter), respectively. The median 3TC area under the curve from 0 to 12 h after
      the last drug intake were 5.6 mg . h/liter (IQR, 4.1 to 7.8 mg . h/liter), 5.9 mg
      . h/liter (IQR, 5.1 to 7.5 mg . h/liter), and 7.3 mg . h/liter (IQR, 4.9 to 8.5
      mg . h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses
      recommended by the WHO would have resulted in a higher proportion of infants
      achieving the targets. However, no HIV-1 infection was reported among these
      infants. These results suggest that the prophylactic targets for both 3TC and LPV
      may be lower than the therapeutic ones. For treatment, the WHO dosing guidelines
      should be suitable to maintain values above the therapeutic pharmacokinetic
      targets in most infants. (This study has been registered at ClinicalTrials.gov
      under identifier NCT00640263.).

PMID- 27895017
TI  - Molecular Investigation of Resistance to Second-Line Injectable Drugs in
      Multidrug-Resistant Clinical Isolates of Mycobacterium tuberculosis in France.
AB  - The second-line injectable drugs (SLID, i.e., amikacin, kanamycin, capreomycin)
      are key drugs for the treatment of multidrug-resistant tuberculosis. Mutations in
      rrs region 1400, tlyA, and eis promoter are associated with resistance to SLID,
      to capreomycin, and to kanamycin, respectively. In this study, the sequencing
      data of SLID resistance-associated genes were compared to the results of
      phenotypic drug susceptibility testing by the proportion method for the SLID in
      206 multidrug-resistant clinical isolates of Mycobacterium tuberculosis collected
      in France. Among the 153 isolates susceptible to the 3 SLID, 145 showed no
      mutation, 1 harbored T1404C and G1473A mutations in rrs, and 7 had an eis
      promoter mutation. Among the 53 strains resistant to at least 1 of the SLID,
      mutations in rrs accounted for resistance to amikacin, capreomycin, and kanamycin
      for 81%, 75%, and 44% of the isolates, respectively, while mutations in eis
      promoter were detected in 44% of the isolates resistant to kanamycin. In
      contrast, no mutations in tlyA were observed in the isolates resistant to
      capreomycin. The discrepancies observed between the genotypic (on the primary
      culture) and phenotypic drug susceptibility testing were explained by (i)
      resistance to SLID with MICs close to the critical concentration used for routine
      DST and not detected by phenotypic testing (n = 8, 15% of SLID-resistant
      strains), (ii) low-frequency heteroresistance not detected by sequencing of drug
      resistance-associated genes on the primary culture (n = 8, 15% of SLID-resistant
      strains), and (iii) other resistance mechanisms not yet characterized (n = 7, 13%
      of SLID-resistant strains).

PMID- 27895018
TI  - Occurrence of Diverse AbGRI1-Type Genomic Islands in Acinetobacter baumannii
      Global Clone 2 Isolates from South Korea.
AB  - In this study, we analyzed the frequency of the AbGRI1-type genomic island (GI)
      and its association with genotypes. We obtained 130 Acinetobacter baumannii
      isolates causing bloodstream infections from patients in South Korea.
      Antimicrobial susceptibility testing and multilocus sequence typing were
      performed. The presence of AbGRI1-type GIs and their structures were determined
      by sequential PCR and sequencing. Ninety-eight isolates (75.3%) representing 14
      sequence types (STs) belonged to clonal complex 208 (CC208), corresponding to
      global clone 2 (GC2). AbGRI1-type GIs interrupted the comM gene in 107 isolates
      (82.4%). Four types of GIs were identified: Tn6022 (50 isolates; 46.7%), AbaR4
      (23 isolates; 21.5%), Tn6166 (10 isolates; 9.3%), and Tn6166/Tn2006 (24 isolates;
      22.4%). In the 50 isolates with Tn6022, Tn2006 or Tn2008B, both containing ISAba1
      blaOXA-23, was present in sites other than GIs in 3 or 28 isolates, respectively.
      In the 10 isolates with Tn6166, Tn2008B was identified in one isolate. AbGRI1
      type GIs were identified nearly exclusively in CC208 isolates, with the exception
      of nine non-CC208 isolates (AbaR4 in eight ST229 isolates and Tn6022 in one
      ST1244 isolate). Within CC208 isolates, there was evidence of frequent
      recombination events, in both housekeeping genes and AbGRI1-type GIs,
      contributing to genotype diversification and the emergence of carbapenem
      resistance.

PMID- 27895019
TI  - Nephrotoxicity during Vancomycin Therapy in Combination with Piperacillin
      Tazobactam or Cefepime.
AB  - Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in
      the incidence of acute kidney injury (AKI) when it is combined with
      antipseudomonal beta-lactams. This study compared the incidence of AKI associated
      with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a
      retrospective, matched cohort study that was conducted at an academic medical
      center between September 2010 and September 2014 and that included adult patients
      without severe chronic or structural kidney disease, dialysis, pregnancy, cystic
      fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h.
      The primary outcome was the difference in the AKI incidence between the TZP-VAN
      and FEP-VAN groups, evaluated using the risk, injury, failure, loss of kidney
      function, and end-stage kidney disease (RIFLE) criteria. Patients in the two
      groups were matched on the basis of age, sex, severity of illness, baseline
      creatinine clearance, hypotension, number of nephrotoxicity risk factors, and
      intravenous contrast exposure. In total, 4,193 patients met all inclusion
      criteria (3,605 received TZP-VAN and 588 received FEP-VAN). The unadjusted AKI
      incidence was 21.4% in patients receiving TZP-VAN, whereas it was 12.6% in
      patients receiving FEP-VAN (P < 0.001). After the patients were matched, 1,633
      patients receiving TZP-VAN and 578 patients receiving FEP-VAN were evaluated. The
      AKI incidence remained higher in patients receiving TZP-VAN than in those
      receiving FEP-VAN (21.4% versus 12.5%, P < 0.0001). This trend remained true for
      all classifications of the RIFLE criteria. After controlling for remaining
      confounders, TZP-VAN therapy was associated with 2.18 times the odds of AKI than
      FEP-VAN therapy (95% confidence interval, 1.64 to 2.94 times) in logistic
      regression. AKI was significantly more common in patients receiving vancomycin in
      combination with piperacillin-tazobactam than in those receiving vancomycin in
      combination with cefepime. This finding reinforces the need for the judicious use
      of combination empirical antimicrobial therapy.

PMID- 27895020
TI  - A Naturally Occurring Single Nucleotide Polymorphism in a Multicopy Plasmid
      Produces a Reversible Increase in Antibiotic Resistance.
AB  - ColE1 plasmids are small mobilizable replicons that play an important role in the
      spread of antibiotic resistance in Pasteurellaceae In this study, we describe how
      a natural single nucleotide polymorphism (SNP) near the origin of replication of
      the ColE1-type plasmid pB1000 found in a Pasteurella multocida clinical isolate
      generates two independent plasmid variants able to coexist in the same cell
      simultaneously. Using the Haemophilus influenzae Rd KW20 strain as a model
      system, we combined antibiotic susceptibility tests, quantitative PCRs,
      competition assays, and experimental evolution to characterize the consequences
      of the coexistence of the pB1000 plasmid variants. This coexistence produced an
      increase of the total plasmid copy number (PCN) in the host bacteria, leading to
      a rise in both the antibiotic resistance level and the metabolic burden produced
      by pB1000. Using experimental evolution, we showed that in the presence of
      ampicillin, the bacteria maintained both plasmid variants for 300 generations. In
      the absence of antibiotics, on the other hand, the bacteria are capable of
      reverting to the single-plasmid genotype via the loss of one of the plasmid
      variants. Our results revealed how a single mutation in plasmid pB1000 provides
      the bacterial host with a mechanism to increase the PCN and, consequently, the
      ampicillin resistance level. Crucially, this mechanism can be rapidly reversed to
      avoid the extra cost entailed by the increased PCN in the absence of antibiotics.

PMID- 27895022
TI  - Inhibition of Plasmodium Liver Infection by Ivermectin.
AB  - Avermectins are powerful endectocides with an established potential to reduce the
      incidence of vector-borne diseases. Here, we show that several avermectins
      inhibit the hepatic stage of Plasmodium infection in vitro Notably, ivermectin
      potently inhibits liver infection in vivo by impairing parasite development
      inside hepatocytes. This impairment has a clear impact on the ensuing blood stage
      parasitemia, reducing disease severity and enhancing host survival. Ivermectin
      has been proposed as a tool to control malaria transmission because of its
      effects on the mosquito vector. Our study extends the effect of ivermectin to the
      early stages of mammalian host infection and supports the inclusion of this
      multipurpose drug in malaria control strategies.

PMID- 27895023
TI  - Pleiotropic Effects of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9)
      Inhibitors?

PMID- 27895021
TI  - In Vitro and In Vivo Activities of Sulfur-Containing Linear Bisphosphonates
      against Apicomplexan Parasites.
AB  - We tested a series of sulfur-containing linear bisphosphonates against Toxoplasma
      gondii, the etiologic agent of toxoplasmosis. The most potent compound (compound
      22; 1-[(n-decylsulfonyl)ethyl]-1,1-bisphosphonic acid) is a sulfone-containing
      compound, which had a 50% effective concentration (EC50) of 0.11 +/- 0.02 MUM
      against intracellular tachyzoites. The compound showed low toxicity when tested
      in tissue culture with a selectivity index of >2,000. Compound 22 also showed
      high activity in vivo in a toxoplasmosis mouse model. The compound inhibited the
      Toxoplasma farnesyl diphosphate synthase (TgFPPS), but the concentration needed
      to inhibit 50% of the enzymatic activity (IC50) was higher than the concentration
      that inhibited 50% of growth. We tested compound 22 against two other
      apicomplexan parasites, Plasmodium falciparum (EC50 of 0.6 +/- 0.01 MUM), the
      agent of malaria, and Cryptosporidium parvum (EC50 of ~65 MUM), the agent of
      cryptosporidiosis. Our results suggest that compound 22 is an excellent novel
      compound that could lead to the development of potent agents against apicomplexan
      parasites.

PMID- 27895025
TI  - Medical Treatment of Aortic Stenosis.
AB  - Untreated, severe, symptomatic aortic stenosis is associated with a dismal
      prognosis. The only treatment shown to improve survival is aortic valve
      replacement; however, before symptoms occur, aortic stenosis is preceded by a
      silent, latent phase characterized by a slow progression at the molecular,
      cellular, and tissue levels. In theory, specific medical therapy should halt
      aortic stenosis progression, reduce its hemodynamic repercussions on left
      ventricular function and remodeling, and improve clinical outcomes. In the
      present report, we performed a systematic review of studies focusing on the
      medical treatment of patients with aortic stenosis. Lipid-lowering therapy,
      antihypertensive drugs, and anticalcific therapy have been the main drug classes
      studied in this setting and are reviewed in depth. A critical appraisal of the
      preclinical and clinical evidence is provided, and future research avenues are
      presented.

PMID- 27895024
TI  - The Role of Calcium/Calmodulin-Dependent Protein Kinase II Activation in
      Hypertrophic Cardiomyopathy.

PMID- 27895026
TI  - Impact of Body Mass Index on the Accuracy of N-Terminal Pro-Brain Natriuretic
      Peptide and Brain Natriuretic Peptide for Predicting Outcomes in Patients With
      Chronic Heart Failure and Reduced Ejection Fraction: Insights From the PARADIGM
      HF Study (Prospective Comparison of ARNI With ACEI to Determine Impact on Global
      Mortality and Morbidity in Heart Failure Trial).

PMID- 27895027
TI  - Letter by Escobar et al Regarding Article, "On-Treatment Outcomes in Patients
      With Worsening Renal Function With Rivaroxaban Compared With Warfarin: Insights
      From ROCKET AF".

PMID- 27895028
TI  - Response by Fordyce et al to Letter Regarding Article, "On-Treatment Outcomes in
      Patients With Worsening Renal Function With Rivaroxaban Compared With Warfarin:
      Insights From ROCKET AF".

PMID- 27895029
TI  - Correction to: Recommended Dietary Pattern to Achieve Adherence to the American
      Heart Association/American College of Cardiology (AHA/ACC) Guidelines: A
      Scientific Statement From the American Heart Association.

PMID- 27895030
TI  - We need clear health messages about exercise.

PMID- 27895031
TI  - One in three with mild cognitive impairment has depression, review finds.

PMID- 27895032
TI  - Molecular Pathways: Receptor Ectodomain Shedding in Treatment, Resistance, and
      Monitoring of Cancer.
AB  - Proteases known as sheddases cleave the extracellular domains of their substrates
      from the cell surface. The A Disintegrin and Metalloproteinases ADAM10 and ADAM17
      are among the most prominent sheddases, being widely expressed in many tissues,
      frequently overexpressed in cancer, and promiscuously cleaving diverse
      substrates. It is increasingly clear that the proteolytic shedding of
      transmembrane receptors impacts pathophysiology and drug response. Receptor
      substrates of sheddases include the cytokine receptors TNFR1 and IL6R; the Notch
      receptors; type-I and -III TGFbeta receptors; receptor tyrosine kinases (RTK)
      such as HER2, HER4, and VEGFR2; and, in particular, MET and TAM-family RTKs AXL
      and Mer (MerTK). Activation of receptor shedding by mechanical cues, hypoxia,
      radiation, and phosphosignaling offers insight into mechanisms of drug
      resistance. This particularly holds for kinase inhibitors targeting BRAF (such as
      vemurafenib and dabrafenib) and MEK (such as trametinib and cobimetinib), along
      with direct sheddase inhibitors. Receptor proteolysis can be detected in patient
      fluids and is especially relevant in melanoma, glioblastoma, lung cancer, and
      triple-negative breast cancer where RTK substrates, MAPK signaling, and ADAMs are
      frequently dysregulated. Translatable strategies to exploit receptor shedding
      include combination kinase inhibitor regimens, recombinant decoy receptors based
      on endogenous counterparts, and, potentially, immunotherapy. Clin Cancer Res;
      23(3); 623-9. (c)2016 AACR.

PMID- 27895034
TI  - Hospitals overwhelmed with patients after "thunderstorm asthma" hits Melbourne.

PMID- 27895036
TI  - Doctor alleged to have performed "designer vagina" surgery won't be prosecuted.

PMID- 27895035
TI  - MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions.
AB  - RATIONALE: In the search for markers and modulators of vascular disease,
      microRNAs (miRNAs) have emerged as potent therapeutic targets. OBJECTIVE: To
      investigate miRNAs of clinical interest in patients with unstable carotid
      stenosis at risk of stroke. METHODS AND RESULTS: Using patient material from the
      BiKE (Biobank of Karolinska Endarterectomies), we profiled miRNA expression in
      patients with stable versus unstable carotid plaque. A polymerase chain reaction
      based miRNA array of plasma, sampled at the carotid lesion site, identified 8
      deregulated miRNAs (miR-15b, miR-29c, miR-30c/d, miR-150, miR-191, miR-210, and
      miR-500). miR-210 was the most significantly downregulated miRNA in local plasma
      material. Laser capture microdissection and in situ hybridization revealed a
      distinct localization of miR-210 in fibrous caps. We confirmed that miR-210
      directly targets the tumor suppressor gene APC (adenomatous polyposis coli),
      thereby affecting Wnt (Wingless-related integration site) signaling and
      regulating smooth muscle cell survival, as well as differentiation in advanced
      atherosclerotic lesions. Substantial changes in arterial miR-210 were detectable
      in 2 rodent models of vascular remodeling and plaque rupture. Modulating miR-210
      in vitro and in vivo improved fibrous cap stability with implications for
      vascular disease. CONCLUSIONS: An unstable carotid plaque at risk of stroke is
      characterized by low expression of miR-210. miR-210 contributes to stabilizing
      carotid plaques through inhibition of APC, ensuring smooth muscle cell survival.
      We present local delivery of miR-210 as a therapeutic approach for prevention of
      atherothrombotic vascular events.

PMID- 27895037
TI  - Margaret McCartney: Evidence in a post-truth world.

PMID- 27895033
TI  - Molecular Pathways: Deciphering Mechanisms of Resistance to Macrophage-Targeted
      Therapies.
AB  - Tumor-associated macrophages (TAMs) are a major cellular component of numerous
      tumor types. TAM-targeted therapies include depletion strategies, inhibiting
      their effector functions or reprogramming toward an antitumorigenic phenotype,
      with varying degrees of efficacy. Here, we review preclinical and clinical
      strategies to target macrophages in cancer and discuss potential explanations for
      why some strategies are effective while other approaches have shown limited
      success. Clin Cancer Res; 23(4); 876-84. (c)2016 AACR.

PMID- 27895038
TI  - The Fragility of Statistically Significant Findings From Randomized Trials in
      Sports Surgery: A Systematic Survey.
AB  - BACKGROUND: High-quality, evidence-based orthopaedic care relies on the
      generation and translation of robust research evidence. The Fragility Index is a
      novel method for evaluating the robustness of statistically significant findings
      from randomized controlled trials (RCTs). It is defined as the minimum number of
      patients in 1 arm of a trial that would have to change status from a nonevent to
      an event to alter the results of the trial from statistically significant to
      nonsignificant. PURPOSE: To calculate the Fragility Index of statistically
      significant results from clinical trials in sports medicine and arthroscopic
      surgery to characterize the robustness of the RCTs in these fields. METHODS: A
      search was conducted in Medline, EMBASE, and PubMed for RCTs related to sports
      medicine and arthroscopic surgery from January 1, 2005, to October 30, 2015. Two
      reviewers independently assessed titles and abstracts for study eligibility,
      performed data extraction, and assessed risk of bias. The Fragility Index was
      calculated using the Fisher exact test for all statistically significant
      dichotomous outcomes from parallel-group RCTs. Bivariate correlation was
      performed to evaluate associations between the Fragility Index and trial
      characteristics. RESULTS: A total of 48 RCTs were included. The median sample
      size was 64 (interquartile range [IQR], 48.5-89.5), and the median total number
      of outcome events was 19 (IQR, 10-27). The median Fragility Index was 2 (IQR, 1
      2.8), meaning that changing 2 patients from a nonevent to an event in the
      treatment arm changed the result to a statistically nonsignificant result, or P
      >= .05. CONCLUSION: Most statistically significant RCTs in sports medicine and
      arthroscopic surgery are not robust because their statistical significance can be
      reversed by changing the outcome status on only a few patients in 1 treatment
      group. Future work is required to determine whether routine reporting of the
      Fragility Index enhances clinicians' ability to detect trial results that should
      be viewed cautiously.

PMID- 27895039
TI  - Region-Specific Effect of the Decellularized Meniscus Extracellular Matrix on
      Mesenchymal Stem Cell-Based Meniscus Tissue Engineering.
AB  - BACKGROUND: The meniscus is the most commonly injured knee structure, and
      surgical repair is often ineffective. Tissue engineering-based repair or
      regeneration may provide a needed solution. Decellularized, tissue-derived
      extracellular matrices (ECMs) have received attention for their potential use as
      tissue-engineered scaffolds. In considering meniscus-derived ECMs (mECMs) for
      meniscus tissue engineering, it is noteworthy that the inner and outer regions of
      the meniscus have different structural and biochemical features, potentially
      directing the differentiation of cells toward region-specific phenotypes.
      PURPOSE: To investigate the applicability of mECMs for meniscus tissue
      engineering by specifically comparing region-dependent effects of mECMs on 3
      dimensional constructs seeded with human bone marrow mesenchymal stem cells
      (hBMSCs). STUDY DESIGN: Controlled laboratory study. METHODS: Bovine menisci were
      divided into inner and outer halves and were minced, treated with Triton X-100
      and DNase, and extracted with urea. Then, hBMSCs (1 * 106 cells/mL) were
      encapsulated in a photo-cross-linked 10% polyethylene glycol diacrylate scaffold
      containing mECMs (60 MUg/mL) derived from either the inner or outer meniscus,
      with an ECM-free scaffold as a control. The cell-seeded constructs were cultured
      with chondrogenic medium containing recombinant human transforming growth factor
      beta3 (TGF-beta3) and were analyzed for expression of meniscus-associated genes
      as well as for the collagen (hydroxyproline) and glycosaminoglycan content as a
      function of time. RESULTS: Decellularization was verified by the absence of 4',6
      diamidino-2-phenylindole (DAPI)-stained cell nuclei and a reduction in the DNA
      content. Quantitative real-time polymerase chain reaction showed that collagen
      type I expression was significantly higher in the outer mECM group than in the
      other groups, while collagen type II and aggrecan expression was highest in the
      inner mECM group. The collagen (hydroxyproline) content was highest in the outer
      mECM group, while the glycosaminoglycan content was higher in both the inner and
      outer mECM groups compared with the control group. CONCLUSION: These results
      showed that the inner mECM enhances the fibrocartilaginous differentiation of
      hBMSCs, while the outer mECM promotes a more fibroblastic phenotype. Our findings
      support the feasibility of fabricating bioactive scaffolds using region-specific
      mECM preparations for meniscus tissue engineering. CLINICAL RELEVANCE: This is
      the first report to demonstrate the feasibility of applying region-specific mECMs
      for the engineering of meniscus implants capable of reproducing the biphasic,
      anatomic, and biochemical characteristics of the meniscus, features that should
      contribute to the feasibility of their clinical application.

PMID- 27895040
TI  - The role of non-invasive cardiovascular imaging in the assessment of
      cardiovascular risk in rheumatoid arthritis: where we are and where we need to
      be.
AB  - This review assesses the risk assessment of cardiovascular disease (CVD) in
      rheumatoid arthritis (RA) and how non-invasive imaging modalities may improve
      risk stratification in future. RA is common and patients are at greater risk of
      CVD than the general population. Cardiovascular (CV) risk stratification is
      recommended in European guidelines for patients at high and very high CV risk in
      order to commence preventative therapy. Ideally, such an assessment should be
      carried out immediately after diagnosis and as part of ongoing long-term patient
      care in order to improve patient outcomes. The risk profile in RA is different
      from the general population and is not well estimated using conventional clinical
      CVD risk algorithms, particularly in patients estimated as intermediate CVD risk.
      Non-invasive imaging techniques may therefore play an important role in improving
      risk assessment. However, there are currently very limited prognostic data
      specific to patients with RA to guide clinicians in risk stratification using
      these imaging techniques. RA is associated with increased risk of CV mortality,
      mainly attributable to atherosclerotic disease, though in addition, RA is
      associated with many other disease processes which further contribute to
      increased CV mortality. There is reasonable evidence for using carotid ultrasound
      in patients estimated to be at intermediate risk of CV mortality using clinical
      CVD risk algorithms. Newer imaging techniques such as cardiovascular magnetic
      resonance and CT offer the potential to improve risk stratification further;
      however, longitudinal data with hard CVD outcomes are currently lacking.

PMID- 27895041
TI  - Infections and the risk of incident giant cell arteritis: a population-based,
      case-control study.
AB  - OBJECTIVES: Alterations in the immune system and infections are suspected to
      increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has
      been directly implicated in the pathogenesis of GCA. We examined the association
      between prior infections, in particular herpes zoster, and incident GCA in a
      population-based cohort. METHODS: A nested case-control study was performed using
      an electronic database from the UK. Cases with newly diagnosed GCA were
      identified using a validated algorithm and compared with age-matched, sex-matched
      and practice-matched controls. Conditional logistic regression was used to
      examine the relationship between any infection or herpes zoster infection on the
      development of GCA after adjusting for potential confounders; results were
      expressed as incidence rate ratios (IRRs). RESULTS: There were 4559 cases of GCA
      and 22 795 controls. Any prior infection and herpes zoster were associated with
      incident GCA (IRR 1.26 (95% CI 1.16 to 1.36), p<0.01; and 1.17 (95% CI 1.04 to
      1.32), p<0.01, respectively). A greater number of infections was associated with
      a higher risk of developing GCA (IRR for 1, 2-4 and >=5 infections was 1.28, 1.60
      and 2.18, respectively). CONCLUSIONS: Antecedent infections and, to a lesser
      extent, herpes zoster infections are modestly associated with incident GCA. These
      data provide population-level support for the hypothesis that long-standing
      alterations of the immune system are associated with susceptibility to GCA and
      suggest that herpes zoster is unlikely to play a major causal role in the
      pathogenesis of GCA.

PMID- 27895042
TI  - Prognostic Value of Cardiac Troponin T and Sex in Patients Undergoing Elective
      Percutaneous Coronary Intervention.
AB  - BACKGROUND: In patients with stable coronary artery disease undergoing elective
      percutaneous coronary intervention, the prognostic value of high-sensitivity
      cardiac troponin T (hs-cTnT) and the influence of sex remain poorly defined.
      METHODS AND RESULTS: Consecutive patients with stable coronary artery disease who
      underwent elective percutaneous coronary intervention were included. Primary
      endpoint was all-cause mortality. Unadjusted hazard ratio (HR) in overall and sex
      specific population and multivariable adjusted HR were calculated by using Cox
      proportional hazard models. In a total of 5626 patients, elevated hs-cTnT levels,
      more than the sex-specific 99th percentile upper reference limit of normal (URL),
      were observed in 2221 patients (39%) at baseline. During follow-up (median, 14.5
      months; 25th-75th percentiles, 6.4-27.2 months), 265 patients died. Mortality was
      higher in patients with the sex-specific 99th percentile URL compared to those
      with normal hs-cTnT (17.3% vs 3.4%; HR=6.10; 95% CI, 4.58-8.14; P<0.001). hs-cTnT
      was an independent predictor of mortality in multivariable adjusted models. The C
      statistic was significantly increased by adding hs-cTnT to the basic prediction
      model for mortality (0.793-0.815; P<0.001). There was a significant interaction
      between hs-cTnT and sex on mortality. Differences in all-cause mortality between
      patients with more than the sex-specific 99th percentile URL and those with
      normal hs-cTnT were numerically larger in male than female patients (male,
      HR=6.45; 95% CI, 4.68-8.87, P<0.001; female, HR=4.29, 95% CI, 2.36-9.03;
      P<0.001). CONCLUSIONS: In patients with stable coronary artery disease undergoing
      elective percutaneous coronary intervention, preprocedural hs-cTnT was a strong
      predictor of mortality in both men and women.

PMID- 27895043
TI  - Impact of Alcohol Consumption on the Outcome of Catheter Ablation in Patients
      With Paroxysmal Atrial Fibrillation.
AB  - BACKGROUND: Although several studies have reported an association between atrial
      fibrillation (AF) and alcohol, the impact of alcohol consumption on the outcome
      after catheter ablation (CA) for AF has not been discussed. We aimed to elucidate
      the effect of alcohol consumption on the outcome of CA for paroxysmal AF. METHODS
      AND RESULTS: We examined 1361 consecutive patients with paroxysmal AF (mean age,
      61+/-11 years, 334 women) who underwent CA, including 623 (45.8%) patients who
      consumed alcohol. The clinical characteristics and outcomes of CA were compared
      between patients who did and did not consume alcohol. No significant differences
      were seen in the left atrial size, duration of AF history, and incidence of
      nonpulmonary vein foci between 2 groups (P=NS). Although the AF recurrence-free
      rate after the initial CA was higher in patients who did not consume alcohol
      (261/623 [41.9%] versus 252/738 [34.1%]; mean follow-up, 44.4+/-30.7 months;
      P=0.003), the outcome after the final CA was similar between 2 groups (patients
      who consumed alcohol: 111/628 [17.7%] versus patients who did not consume
      alcohol: 138/738 [18.7%]; mean follow-up, 53.1+/-25.8 months; P=0.67). The
      frequency (hazard ratio 1.07 per 1 day/week increase, CI 1.00-1.15, P=0.04) of
      alcohol consumption was significantly associated with AF recurrence after CA.
      CONCLUSIONS: The frequency of alcohol consumption may be associated with AF
      recurrence after the initial CA for paroxysmal AF, but it may not affect the
      outcome after the final CA.

PMID- 27895044
TI  - Polymorphisms in the GNAS Gene as Predictors of Ventricular Tachyarrhythmias and
      Sudden Cardiac Death: Results From the DISCOVERY Trial and Oregon Sudden
      Unexpected Death Study.
AB  - BACKGROUND: Population-based studies suggest that genetic factors contribute to
      sudden cardiac death (SCD). METHODS AND RESULTS: In the first part of the present
      study (Diagnostic Data Influence on Disease Management and Relation of Genetic
      Polymorphisms to Ventricular Tachy-arrhythmia in ICD Patients [DISCOVERY] trial)
      Cox regression was done to determine if 7 single-nucleotide polymorphisms (SNPs)
      in 3 genes coding G-protein subunits (GNB3, GNAQ, GNAS) were associated with
      ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable
      cardioverter-defibrillator (ICD). In the second part of the study, SNPs
      significantly associated with VT were further investigated in 1335 subjects from
      the Oregon SUDS, a community-based study analyzing causes of SCD. In the
      DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant
      in the prospective screening and significantly associated with VT when viewed as
      recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11
      1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18-2.09], P=0.002). TT
      genotype in either SNP was associated with a HR of 1.58 (CI 1.26-1.99)
      (P=0.0001). In the Oregon SUDS cohort significant evidence for association with
      SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05
      1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10-2.13]) genetic models.
      CONCLUSIONS: GNAS harbors 2 SNPs that were associated with an increased risk for
      VT in ICD patients, of which 1 was successfully replicated in a community-based
      population of SCD cases. To the best of our knowledge, this is the first example
      of a gene variant identified by ICD VT monitoring as a surrogate parameter for
      SCD and also confirmed in the general population. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00478933.

PMID- 27895045
TI  - Cardiorespiratory Fitness and Highly Sensitive Cardiac Troponin Levels in a
      Preventive Medicine Cohort.
AB  - BACKGROUND: Cardiorespiratory fitness (CRF) and highly sensitive cardiac troponin
      T (hs-cTnT) are associated with risk of all-cause and cardiovascular mortality as
      well as incident heart failure. A link of low CRF to subclinical cardiac injury
      may explain this association. We hypothesized that CRF would be inversely
      associated with hs-cTnT measured in healthy adults over age 50. METHODS AND
      RESULTS: We evaluated 2498 participants (24.7% female, mean age 58.7 years) from
      the Cooper Center Longitudinal Study between August 2008 and January 2012. Plasma
      specimens obtained shortly before CRF estimates by Balke treadmill testing were
      used for hs-cTnT assays. CRF was grouped into low CRF (category 1), moderate CRF
      (categories 2-3), and high CRF (categories 4-5). Multivariable logistic
      regression was used to estimate the association of CRF with hs-cTnT. The
      prevalence of measurable hs-cTnT (>=3 ng/L) was 78.5%. In multivariable analyses,
      low-fit individuals were significantly more likely than high-fit individuals to
      have elevated hs-cTnT (>=14 ng/L) (odds ratio 2.47, 95% CI 1.10-5.36).
      CONCLUSIONS: In healthy older adults, CRF is inversely associated with hs-cTnT
      level adjusted for other risk factors. Prospective studies are needed to evaluate
      whether improving CRF is effective in preventing subclinical cardiac injury.

PMID- 27895046
TI  - Gene silencing of Nox4 by CpG island methylation during hepatocarcinogenesis in
      rats.
AB  - The association between the downregulation of genes and DNA methylation in their
      CpG islands has been extensively studied as a mechanism that favors
      carcinogenesis. The objective of this study was to analyze the methylation of a
      set of genes selected based on their microarray expression profiles during the
      process of hepatocarcinogenesis. Rats were euthanized at: 24 h, 7, 11, 16 and 30
      days and 5, 9, 12 and 18 months post-treatment. We evaluated the methylation
      status in the CpG islands of four deregulated genes (Casp3, Cldn1, Pex11a and
      Nox4) using methylation-sensitive high-resolution melting technology for the
      samples obtained from different stages of hepatocarcinogenesis. We did not
      observe methylation in Casp3, Cldn1 or Pex11a. However, Nox4 exhibited altered
      methylation patterns, reaching a maximum of 10%, even during the early stages of
      hepatocarcinogenesis. We observed downregulation of mRNA and protein of Nox4
      (97.5% and 40%, respectively) after the first carcinogenic stimulus relative to
      the untreated samples. Our results suggest that Nox4 downregulation is associated
      with DNA methylation of the CpG island in its promoter. We propose that
      methylation is a mechanism that can silence the expression of Nox4, which could
      contribute to the acquisition of neoplastic characteristics during
      hepatocarcinogenesis in rats.

PMID- 27895047
TI  - Innovative approaches to establish and characterize primary cultures: an ex vivo
      3D system and the zebrafish model.
AB  - Patient-derived specimens are an invaluable resource to investigate tumor
      biology. However, in vivo studies on primary cultures are often limited by the
      small amount of material available, while conventional in vitro systems might
      alter the features and behavior that characterize cancer cells. We present our
      data obtained on primary dedifferentiated liposarcoma cells cultured in a 3D
      scaffold-based system and injected into a zebrafish model. Primary cells were
      characterized in vitro for their morphological features, sensitivity to drugs and
      biomarker expression, and in vivo for their engraftment and invasiveness
      abilities. The 3D culture showed a higher enrichment in cancer cells than the
      standard monolayer culture and a better preservation of liposarcoma-associated
      markers. We also successfully grafted primary cells into zebrafish, showing their
      local migratory and invasive abilities. Our work provides proof of concept of the
      ability of 3D cultures to maintain the original phenotype of ex vivo cells, and
      highlights the potential of the zebrafish model to provide a versatile in vivo
      system for studies with limited biological material. Such models could be used in
      translational research studies for biomolecular analyses, drug screenings and
      tumor aggressiveness assays.

PMID- 27895049
TI  - Daily feeding and protein metabolism rhythms in Senegalese sole post-larvae.
AB  - Fish hatcheries must adapt larval feeding protocols to feeding behavior and
      metabolism patterns to obtain more efficient feed utilization. Fish larvae
      exhibit daily ingesting rhythms rather than ingesting food continuously
      throughout the day. The aim of this study was to determine the daily patterns of
      feed intake, protein digestibility, protein retention and catabolism in
      Senegalese sole post-larvae (Solea senegalensis; 33 days post-hatching) using 14C
      labeled Artemia protein and incubation in metabolic chambers. Sole post-larvae
      were fed at 09:00, 15:00, 21:00, 03:00 and 09:00+1 day; and those fed at 09:00,
      21:00, 03:00 and 09:00+1 day showed significantly higher feed intake than post
      larvae fed at 15:00 h (P=0.000). Digestibility and evacuation rate of ingested
      protein did not change during the whole cycle (P=0.114); however, post-larvae fed
      at 21:00 and 03:00 h showed the significantly highest protein retention
      efficiency and lowest catabolism (P=0.002). Therefore, results confirm the
      existence of daily rhythmicity in feeding activity and in the utilization of the
      ingested nutrients in Senegalese sole post-larvae.

PMID- 27895048
TI  - Parecoxib inhibits glioblastoma cell proliferation, migration and invasion by
      upregulating miRNA-29c.
AB  - Glioblastoma (GBM) is one of the most lethal brain cancers worldwide, and there
      is an urgent need for development of novel therapeutic approaches. Parecoxib is a
      well-known cyclooxygenase-2 (COX-2) inhibitor, and had already been developed for
      postoperative analgesia with high efficacy and low adverse reaction. A recent
      study has suggested that parecoxib potently enhances immunotherapeutic efficacy
      of GBM, but its effects on GBM growth, migration and invasion have not previously
      been studied. In the present study, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] and BrdU (5-bromo-2-deoxyuridine) incorporation
      assays were used to evaluate the cell proliferation of GBM cells. Wound-healing
      and transwell assays were preformed to analyze GBM cell migration and invasion,
      respectively. The results suggested that parecoxib inhibits cell proliferation,
      migration and invasion of GBM cells in a dose-dependent manner. RT-qPCR (real
      time quantitative PCR) analysis demonstrated that miRNA-29c can be significantly
      induced by parecoxib. Furthermore, our data suggests that a miRNA-29c inhibitor
      can significantly attenuate parecoxib's effect on proliferation, migration and
      invasion of GBM. In conclusion, the present study suggests that parecoxib
      inhibits GBM cell proliferation, migration and invasion by upregulating miRNA
      29c.

PMID- 27895050
TI  - Social signals and aversive learning in honey bee drones and workers.
AB  - The dissemination of information is a basic element of group cohesion. In honey
      bees (Apis mellifera Linnaeus 1758), like in other social insects, the principal
      method for colony-wide information exchange is communication via pheromones. This
      medium of communication allows multiple individuals to conduct tasks critical to
      colony survival. Social signaling also establishes conflict at the level of the
      individual who must trade-off between attending to the immediate environment or
      the social demand. In this study we examined this conflict by challenging highly
      social worker honey bees, and less social male drone honey bees undergoing
      aversive training by presenting them with a social stress signal (isopentyl
      acetate, IPA). We utilized IPA exposure methods that caused lower learning
      performance in appetitive learning in workers. Exposure to isopentyl acetate
      (IPA) did not affect performance of drones and had a dose-specific effect on
      worker response, with positive effects diminishing at higher IPA doses. The IPA
      effects are specific because non-social cues, such as the odor cineole, improve
      learning performance in drones, and social homing signals (geraniol) did not have
      a discernible effect on drone or worker performance. We conclude that social
      signals do generate conflict and that response to them is dependent on signal
      relevance to the individual as well as the context. We discuss the effect of
      social signal on learning both related to its social role and potential
      evolutionary history.

PMID- 27895051
TI  - Metabolism and antioxidant defense in the larval chironomid Tanytarsus
      minutipalpus: adjustments to diel variations in the extreme conditions of Lake
      Magadi.
AB  - Insect larvae are reported to be a major component of the simple but highly
      productive trophic web found in Lake Magadi (Kenya, Africa), which is considered
      to be one of the most extreme aquatic environments on Earth. Previous studies
      show that fish must display biochemical and physiological adjustments to thrive
      under the extreme conditions of the lake. However, information for invertebrates
      is lacking. In the present study, the occurrence of the larval chironomid
      Tanytarsus minutipalpus is reported in Lake Magadi for the first time.
      Additionally, changes in larval metabolism and antioxidant defense correlated
      with diel variations in the extremely hostile environmental conditions of the
      lake are described. Wide variations in water temperature (20.2-29.3 degrees C)
      and dissolved oxygen content (3.2-18.6 mg O2 l-1) were observed at different
      times of day, without significant change in water pH (10.0+/-0.03). Temperature
      and dissolved oxygen were higher at 13:00 h (29.3+/-0.4 degrees C and 18.6+/-1.0
      mg O2 l-1) and 19:00 h (29.3+/-0.8 degrees C and 16.2+/-1.6 mg O2 l-1) and lower
      at 01:00 h (21.1+/-0.1 degrees C and 10.7+/-0.03 mg O2 l-1) and 07:00 h (20.2+/
      0.4 degrees C and 3.2+/-0.7 mg O2 l-1). Significant and parallel increases in
      parameters related to metabolism (cholinesterase, glucose, cholesterol, urea,
      creatinine and hemoglobin) and the antioxidant system (SOD, GPx, GR, GSH and
      GSSG) were observed in larvae collected at 13:00 h. In contrast, no significant
      changes were observed in pro-oxidants (ROS and NO), TOSC and oxidative damage
      parameters (LPO and DNA damage). Therefore, the observed increases in temperature
      and dissolved O2 content in Lake Magadi were associated with changes in the
      antioxidant system of T. minutipalpus larvae. Adjustments performed by the
      chironomid larvae were efficient in maintaining body homeostasis, as well as
      protecting biomolecules against oxidative damage, so that oxidative stress did
      not occur. GSH-GSSG and GPx-GR systems appeared to play an essential role in the
      adjustments displayed by the chironomid larvae during the diel changes in the
      extreme conditions of Lake Magadi.

PMID- 27895052
TI  - Evidence toads may modulate landing preparation without predicting impact time.
AB  - Within anurans (frogs and toads), cane toads (Bufo marinus) perform particularly
      controlled landings in which the forelimbs are exclusively used to decelerate and
      stabilize the body after impact. Here we explore how toads achieve dynamic
      stability across a wide range of landing conditions. Specifically, we suggest
      that torques during landing could be reduced by aligning forelimbs with the
      body's instantaneous velocity vector at impact (impact angle). To test whether
      toad forelimb orientation varies with landing conditions, we used high-speed
      video to collect forelimb and body kinematic data from six animals hopping off
      platforms of different heights (0, 5 and 9 cm). We found that toads do align
      forelimbs with the impact angle. Further, toads align forelimbs with the
      instantaneous velocity vector well before landing and then track its changes
      until touchdown. This suggests that toads may be prepared to land well before
      they hit the ground rather than preparing for impact at a specific moment, and
      that they may use a motor control strategy that allows them to perform controlled
      landings without the need to predict impact time.

PMID- 27895054
TI  - Passport to healthcare: NHS charges become the new normal for overseas patients.

PMID- 27895053
TI  - Utilising polymorphisms to achieve allele-specific genome editing in zebrafish.
AB  - The advent of genome editing has significantly altered genetic research,
      including research using the zebrafish model. To better understand the
      selectivity of the commonly used CRISPR/Cas9 system, we investigated single base
      pair mismatches in target sites and examined how they affect genome editing in
      the zebrafish model. Using two different zebrafish strains that have been deep
      sequenced, CRISPR/Cas9 target sites containing polymorphisms between the two
      strains were identified. These strains were crossed (creating heterozygotes at
      polymorphic sites) and CRISPR/Cas9 complexes that perfectly complement one strain
      injected. Sequencing of targeted sites showed biased, allele-specific editing for
      the perfectly complementary sequence in the majority of cases (14/19). To test
      utility, we examined whether phenotypes generated by F0 injection could be
      internally controlled with such polymorphisms. Targeting of genes bmp7a and
      chordin showed reduction in the frequency of phenotypes in injected
      'heterozygotes' compared with injecting the strain with perfect complementarity.
      Next, injecting CRISPR/Cas9 complexes targeting two separate sites created
      deletions, but deletions were biased to selected chromosomes when one CRISPR/Cas9
      target contained a polymorphism. Finally, integration of loxP sequences occurred
      preferentially in alleles with perfect complementarity. These experiments
      demonstrate that single nucleotide polymorphisms (SNPs) present throughout the
      genome can be utilised to increase the efficiency of in cis genome editing using
      CRISPR/Cas9 in the zebrafish model.

PMID- 27895056
TI  - Funds are not reaching frontline services.

PMID- 27895055
TI  - Role of agents for reversing the effects of target-specific oral anticoagulants.
AB  - PURPOSE: The available clinical data on target-specific oral anticoagulant
      (TSOAC) reversal agents that are currently in development or have been approved
      by the Food and Drug Administration (FDA) are reviewed. SUMMARY: The development
      of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented
      benefits and new challenges. One of the main challenges associated with the use
      of TSOACs is the lack of suitable agent-specific reversal agents. Several
      treatment options for the management of life-threatening bleeding events
      associated with TSOAC use, such as fresh frozen plasma, prothrombin complex
      concentrates, and recombinant coagulation factor VIIa, have been used, with
      inconsistent results. Currently, two potential reversal agents for oral direct
      factor Xa inhibitors (andexanet alfa and ciraparantag) are at various stages of
      clinical development. Idarucizumab, a reversal agent for the oral direct thrombin
      inhibitor dabigatran, was approved by FDA in October 2015. Idarucizumab and
      andexanet alfa have been reported to produce anticoagulation reversal effects
      within minutes of administration. Ciraparantag was demonstrated to decrease whole
      blood clotting time to within 10% of baseline values in 10 minutes or less, with
      a return to baseline hemostasis in 10-30 minutes. TSOAC reversal agents have been
      generally well tolerated in clinical trials. CONCLUSION: Idarucizumab and other
      TSOAC reversal agents, such as andexanet alfa and ciraparantag, present the
      potential for consistent and effective treatment and management options when life
      threatening or uncontrolled TSOAC-associated bleeding occurs or when emergency
      surgery is warranted in patients using TSOACs.

PMID- 27895057
TI  - Pfizer could face large fine over pricing of generic phenytoin.

PMID- 27895059
TI  - Developed nations should set an example on accepting funds from infant formula
      companies.

PMID- 27895060
TI  - Human experience isn't multiple choice.

PMID- 27895061
TI  - Five thousand dead and counting: the Philippines' bloody war on drugs.

PMID- 27895062
TI  - Health professionals must be ethnographers.

PMID- 27895063
TI  - Association of eating behaviours with diurnal preference and rotating shift work
      in Japanese female nurses: a cross-sectional study.
AB  - OBJECTIVES: Our study examines differences in eating behaviour between day
      workers and rotating shift workers, and considers whether diurnal preference
      could explain the differences. METHODS: Japanese female nurses were studied (39
      day workers and 123 rotating shift workers, aged 21-63 years) using self
      administered questionnaires. The questionnaires assessed eating behaviours,
      diurnal preference and demographic characteristics. The questionnaire in the
      Guidelines for the management of obesity disease issued by the Japan Society for
      the Study of Obesity was used to obtain scores for the levels of obesity-related
      eating behaviours, including cognition of constitution, motivation for eating,
      eating as a diversion, feeling of satiety, eating style, meal contents and
      temporal eating patterns. The Japanese version of the Morningness-Eveningness
      (ME) questionnaire was used to measure self-rated preference for the degree to
      which people prefer to be active in the morning or the evening (ME). RESULTS: The
      scores for meal contents and temporal eating patterns in rotating shift workers
      were significantly higher than those in day workers. The ME score of rotating
      shift workers was significantly lower, indicating greater eveningness/less
      morningness among rotating shift workers. Multivariate linear regression revealed
      that the ME score was significantly negatively associated with temporal eating
      patterns and showed a negative association with the score for meal contents at a
      trend level, while current work shift was not significantly correlated with the
      scores. CONCLUSIONS: These results suggest that eating behaviours for rotating
      shift workers are associated with a more unbalanced diet and abnormal temporal
      eating patterns and that the associations may be explained by diurnal preference
      rather than by rotating shift work.

PMID- 27895064
TI  - Risk of obstructive sleep apnoea in patients with rheumatoid arthritis: a
      nationwide population-based retrospective cohort study.
AB  - OBJECTIVE: Sleep disorders are prevalent medical disorders in patients with
      rheumatoid arthritis (RA). However, whether patients with RA are at an increased
      risk of developing obstructive sleep apnoea (OSA) is unclear. DESIGN: Using
      population-based retrospective cohort study to examine the risk of OSA in
      patients with RA. SETTING: We used claims data of the National Health Insurance
      Research Database (NHIRD) of Taiwan. PARTICIPANTS: We identified a RA cohort with
      33 418 patients newly diagnosed in 2000-2010 and a randomly selected non-RA
      comparison cohort with 33 418 individuals frequency matched by sex, age and
      diagnosis year. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident OSA was
      estimated by the end of 2011. The HRs of OSA were calculated using the Cox
      proportional hazards regression analysis. RESULTS: The overall incidence rate of
      OSA was 75% greater in the RA cohort than in the non-RA cohort (3.04 vs 1.73/10
      000 person-years, p<0.001), with an adjusted HR (aHR) of 1.75 (95% CI 1.18 to
      2.60). Stratified analyses by sex, age group and comorbidity revealed that the
      incidence rates of OSA associated with RA were higher in all subgroups.
      CONCLUSIONS: This population-based retrospective cohort study suggested that
      patients with RA should be monitored for the risk of developing OSA.

PMID- 27895058
TI  - Diagnosis and management of AML in adults: 2017 ELN recommendations from an
      international expert panel.
AB  - The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis
      and management of acute myeloid leukemia (AML) in adults, published in 2010, has
      found broad acceptance by physicians and investigators caring for patients with
      AML. Recent advances, for example, in the discovery of the genomic landscape of
      the disease, in the development of assays for genetic testing and for detecting
      minimal residual disease (MRD), as well as in the development of novel
      antileukemic agents, prompted an international panel to provide updated evidence-
      and expert opinion-based recommendations. The recommendations include a revised
      version of the ELN genetic categories, a proposal for a response category based
      on MRD status, and criteria for progressive disease.

PMID- 27895066
TI  - Protocol of the Swiss Longitudinal Cohort Study (SWICOS) in rural Switzerland.
AB  - INTRODUCTION: Increased longevity and consequent major changes in demographics
      and population lifestyles necessitate new approaches to reduce the burden of
      ageing-related diseases (including cardiovascular disease) and maintain an
      optimal quality of life. This study aims to examine and longitudinally follow
      health status and disease risk factors in a Swiss rural cohort, evaluating all
      health-related research and practice disciplines to assure development of new
      implementable and successful preventive strategies for healthy ageing. METHODS
      AND OBJECTIVES: Small Swiss villages with low migration rates will be selected
      for this study. 2 villages (Cama/Lostallo) have already been selected as initial
      study sites. All residents (age >=6 years, no upper age limit) are eligible. The
      target enrolment number per village is 300. Examinations and measurements
      encompass medical history, anthropometry, cardiac and vascular health, pulmonary
      function, physical performance, nutritional, mental and emotional status,
      biochemical and molecular analyses. Follow-up examinations (identical to
      baseline) will be performed after 5 and 10 years, and in 10-year intervals
      thereafter. The major objective is to assess, and observe change in, health
      status over time in a prospective manner. Secondary objectives are to: (1)
      identify 'hidden' (asymptomatic and/or unrecognised) health problems which
      enhance risk for chronic diseases; (2) identify barriers to accessing healthcare
      and adapting health behaviours; (3) evaluate efficacy of present preventive
      strategies and recommendations; (4) evaluate knowledge and attitude towards
      ongoing health programmes and public health recommendations; (5) monitor change
      and progress towards the national health objectives; (6) formulate new preventive
      strategies and recommendations based on the findings and knowledge base of the
      past 10 years; (7) formulate models for successful prevention of chronic diseases
      and for healthy ageing. ETHICS AND DISSEMINATION: The Ethics Committee of
      Nordwest-und Zentralschweiz approved this study (EKNZ 2014-209). It is registered
      at ClinicalTrials.gov (NCT02282748). Findings will be disseminated through
      scientific articles/presentations and public events.

PMID- 27895067
TI  - Changes in objectively measured smoking in pregnancy by time and legislative
      changes in Finland: a retrospective cohort study.
AB  - OBJECTIVES: To study the changes in prevalence, characteristics and outcomes of
      pregnant smokers over time and legislative changes. DESIGN AND SETTING:
      Retrospective nationwide cohort. PARTICIPANTS: Our study consisted of 9627
      randomly selected pregnancies from the Finnish Maternity Cohort (1987-2011), with
      demographic characteristics and pregnancy and perinatal data obtained from the
      Medical Birth Registry and early pregnancy serum samples analysed for cotinine
      levels. Women were categorised based on their self-reported smoking status and
      measured cotinine levels (with >=4.73 ng/mL deemed high). Data were stratified to
      three time periods based on legislative changes in the Tobacco Act. PRIMARY AND
      SECONDARY OUTCOME MEASURES: Prevalence of pregnant smokers and demographics, and
      perinatal and pregnancy outcomes of pregnant smokers over time. RESULTS: Overall,
      71.6% of women were non-smokers, 16.2% were active cigarette smokers, 7.7%
      undisclosed smoking but had high cotinine levels and 4.5% were inactive cigarette
      smokers. The prevalence of active cigarette smokers decreased from mid-1990s
      onwards among women aged >=30 years, probably due to the ban of cigarette smoking
      in most workplaces. We observed no changes in the prevalence of inactive smokers
      or women who undisclosed smoking by time or legislative changes.Women who
      undisclosed smoking had similar characteristics and perinatal outcomes as
      inactive and active smokers. Compared with non-smokers, women who undisclosed
      smoking were more likely to be young, unmarried, have a socioeconomic status
      lower than white-collar worker and have a preterm birth. CONCLUSIONS: Women who
      undisclosed smoking were very similar to pregnant cigarette smokers. We observed
      a reduction in the prevalence of active pregnant cigarette smokers after the ban
      of indoor smoking in workplaces and restaurants, mostly among women aged >=30
      years.

PMID- 27895065
TI  - Social determinants and maternal exposure to intimate partner violence of
      obstetric patients with severe maternal morbidity in the intensive care unit: a
      systematic review protocol.
AB  - INTRODUCTION: Maternal mortality is a potentially preventable public health
      issue. Maternal morbidity is increasingly of interest to aid the reduction of
      maternal mortality. Obstetric patients admitted to the intensive care unit (ICU)
      are an important part of the global burden of maternal morbidity. Social
      determinants influence health outcomes of pregnant women. Additionally, intimate
      partner violence has a great negative impact on women's health and pregnancy
      outcome. However, little is known about the contextual and social aspects of
      obstetric patients treated in the ICU. This study aimed to conduct a systematic
      review of the social determinants and exposure to intimate partner violence of
      obstetric patients admitted to an ICU. METHODS AND ANALYSIS: A systematic search
      will be conducted in MEDLINE, CINAHL, ProQuest, LILACS and SciELO from 2000 to
      2016. Studies published in English and Spanish will be identified in relation to
      data reporting on social determinants of health and/or exposure to intimate
      partner violence of obstetric women, treated in the ICU during pregnancy,
      childbirth or within 42 days of the end of pregnancy. Two reviewers will
      independently screen for study eligibility and data extraction. Risk of bias and
      assessment of the quality of the included studies will be performed by using the
      Critical Appraisal Skills Programme (CASP) checklist. Data will be analysed and
      summarised using a narrative description of the available evidence across
      studies. This systematic review protocol will be reported according to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols
      (PRISMA-P) guidelines. ETHICS AND DISSEMINATION: Since this systematic review
      will be based on published studies, ethical approval is not required. Findings
      will be presented at La Trobe University, in Conferences and Congresses, and
      published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42016037492.

PMID- 27895068
TI  - Impact of a dedicated cancer-associated thrombosis service on clinical outcomes:
      a mixed-methods evaluation of a clinical improvement exercise.
AB  - OBJECTIVES: Cancer-associated thrombosis (CAT) complex condition, which may
      present to any healthcare professional and at any point during the cancer
      journey. As such, patients may be managed by a number of specialties, resulting
      in inconsistent practice and suboptimal care. We describe the development of a
      dedicated CAT service and its evaluation. SETTING: Specialist cancer centre,
      district general hospital and primary care. PARTICIPANTS: Patients with CAT and
      their referring clinicians. INTERVENTION: A cross specialty team developed a
      dedicated CAT service , including clear referral pathways, consistent access to
      medicines, patient's information and a specialist clinic. PRIMARY AND SECONDARY
      OUTCOME MEASURES: The service was evaluated using a mixed-methods evaluation ,
      including audits of clinical practice, clinical outcomes, staff surveys and
      qualitative interviewing of patients and healthcare professionals. RESULTS: Data
      from 457 consecutive referrals over an 18-month period were evaluated. The CAT
      service has led to an 88% increase in safe and consistent community prescribing
      of low-molecular-weight heparin, with improved access to specialist advice and
      information. Patients reported improved understanding of their condition,
      enabling better self-management as well as better access to support and
      information. Referring clinicians reported better care standards for their
      patients with improved access to expertise and appropriate management.
      CONCLUSIONS: A dedicated CAT service improves overall standards of care and is
      viewed positively by patients and clinicians alike. Further health economic
      evaluation would enhance the case for establishing this as the standard model of
      care.

PMID- 27895070
TI  - I Forgot: Memory and Medication Adherence in Heart Failure.

PMID- 27895071
TI  - Stenting of Spontaneous Coronary Artery Dissection From a Pathological Point of
      View.

PMID- 27895069
TI  - Association Between Poorer Cognitive Function and Reduced Objectively Monitored
      Medication Adherence in Patients With Heart Failure.
AB  - BACKGROUND: Subclinical cognitive impairment is prevalent in heart failure (HF);
      however, its role in important clinical outcomes, such as HF treatment adherence,
      is unclear. Given the complex polypharmacy in HF treatment, cognitive deficits
      may be important in predicting medication management. Thus, the objective of the
      current study was to examine the impact of cognitive function on medication
      adherence among community-dwelling patients with HF using objective assessments.
      METHODS AND RESULTS: A prospective observational cohort design of 309 community
      dwelling patients with HF (59.7% male, 68.7+/-9.7 years) and no history of
      dementia or neurological disease. Cognition was assessed using a
      neuropsychological battery at baseline. Medication adherence was objectively
      measured for 21 days using an electronic pillbox. Regression analyses tested
      whether attention, executive function, or memory predicted 21-day medication
      adherence. In unadjusted analyses, lower scores on all 3 cognitive domains
      predicted poorer medication adherence (beta=0.52-85; P=0.001-0.009). After
      adjusting for demographic, clinical, and psychosocial variables, memory continued
      to predict medication adherence (beta=0.51; P=0.008), whereas executive function
      (beta=0.24; P=0.075) and attention were no longer a predictor (beta=0.34;
      P=0.131). CONCLUSIONS: Poorer cognitive function, especially in regard to memory,
      predicted reduced medication adherence among patients with HF and no history of
      dementia. This effect remained after adjustment for factors known to predict
      adherence, such as depressed mood, social support, and disease severity level.
      Future studies should examine the link from cognitive impairment and medication
      nonadherence to clinical outcomes (eg, hospitalization and mortality). CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT01461629.

PMID- 27895072
TI  - UK government's autumn statement: no relief for NHS and social care in England.

PMID- 27895073
TI  - Fertility authority must provide evidence for tests and treatments, say
      researchers.

PMID- 27895074
TI  - Patch testing in patients with anal itching.

PMID- 27895075
TI  - Associations of specific types of sports and exercise with all-cause and
      cardiovascular-disease mortality: a cohort study of 80 306 British adults.
AB  - BACKGROUND/AIM: Evidence for the long-term health effects of specific sport
      disciplines is scarce. Therefore, we examined the associations of six different
      types of sport/exercise with all-cause and cardiovascular disease (CVD) mortality
      risk in a large pooled Scottish and English population-based cohort. METHODS: Cox
      proportional hazards regression was used to investigate the associations between
      each exposure and all-cause and CVD mortality with adjustment for potential
      confounders in 80 306 individuals (54% women; mean+/-SD age: 52+/-14 years).
      RESULTS: Significant reductions in all-cause mortality were observed for
      participation in cycling (HR=0.85, 95% CI 0.76 to 0.95), swimming (HR=0.72, 95%
      CI 0.65 to 0.80), racquet sports (HR=0.53, 95% CI 0.40 to 0.69) and aerobics
      (HR=0.73, 95% CI 0.63 to 0.85). No significant associations were found for
      participation in football and running. A significant reduction in CVD mortality
      was observed for participation in swimming (HR=0.59, 95% CI 0.46 to 0.75),
      racquet sports (HR=0.44, 95% CI 0.24 to 0.83) and aerobics (HR=0.64, 95% CI 0.45
      to 0.92), but there were no significant associations for cycling, running and
      football. Variable dose-response patterns between the exposure and the outcomes
      were found across the sport disciplines. CONCLUSIONS: These findings demonstrate
      that participation in specific sports may have significant benefits for public
      health. Future research should aim to further strengthen the sport-specific
      epidemiological evidence base and understanding of how to promote greater sports
      participation.

PMID- 27895076
TI  - Mesothelial Cells Create a Novel Tissue Niche That Facilitates Gastric Cancer
      Invasion.
AB  - Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity.
      In this study, lineage tracing revealed that the PMCs guide cancer cell invasion
      in the gastric wall and in peritoneal metastatic lesions. Serosal PMCs covering
      the stomach surface entered the gastric wall to create a novel niche that favored
      gastric cancer cell invasion. PMC infiltration was induced by incorporation of
      cancer cell-derived, Wnt3a-containing extracellular vesicles. Infiltrated PMCs in
      turn promoted subserosal invasion of cancer cells. Mutual attraction between
      cancer cells and PMCs accelerated tumor invasion in the gastric wall, and PMC-led
      cancer cell invasion in disseminated tumors within the abdominal wall and
      diaphragm. Addition of the carboxyl terminus of Dickkopf-1 attenuated directional
      invasion of PMCs toward cancer cells both in vitro and in the gastric wall in
      vivo PMCs were sensitive to the aldehyde dehydrogenase (ALDH) inhibitor
      disulfiram (DSF), as ALDH activity is elevated in PMCs. Wnt3a upregulated ALDH,
      and addition of DSF inhibited the invasive properties of PMCs, whereas DSF
      pretreatment suppressed gastric infiltration of PMCs and subserosal invasion by
      cancer cells. Our results suggest that stabilization of PMCs may become an
      effective therapy for the prevention of local invasion and metastasis of gastric
      cancer. Cancer Res; 77(3); 684-95. (c)2016 AACR.

PMID- 27895077
TI  - Acquired male urethral diverticulum: a rare entity treated in a one-stage
      procedure.
AB  - Acquired male urethral diverticulum is a rare entity with most of the literature
      revolving around case reports or small case series. Up to two-thirds of cases are
      acquired, mostly as a result of trauma, stricture or infection. Infrequently,
      some cases develop as a complication of urological procedures, or even penile
      clamping. We present the case of an adult male with lower urinary tract symptoms,
      recurrent urinary infections and a history of multiple surgeries to treat a
      complicated perineal fistulae disease. With the help of imaging techniques, a
      bulbar urethral diverticulum was discovered. Owing to the symptomatic nature of
      the diverticulum, an open procedure was performed with excision and primary
      urethral anastomosis. No urinary symptoms were reported and follow-up imaging and
      flowmetry demonstrated very good functional outcome.

PMID- 27895078
TI  - Why so blue? A case of neonatal cyanosis due to congenital methaemoglobinaemia
      (HbM Iwate).

PMID- 27895080
TI  - Unusual cause of pleuritic chest pain in a child.
AB  - We present the case of a 5-year-old boy with hereditary multiple exostoses who
      presented with left-sided pleuritic chest pain. A CT scan of the chest revealed
      an intrathoracic exostosis in close association with the heart.

PMID- 27895079
TI  - Anterior chamber exudation in chronic myeloid leukaemia.
AB  - Anterior chamber leukaemic hypopyon is a rare occurrence in chronic myeloid
      leukaemia. We discuss two cases marked by rapid exudation inside the anterior
      chamber, which were subsequently diagnosed as chronic myeloid leukaemia. The
      hypopyon in both the cases resolved on induction of chemotherapy.

PMID- 27895081
TI  - Malignant melanoma of cervix.
AB  - A 68-year-old woman presented with symptoms of bleeding per vaginum. On
      examination, a growth was seen in the cervix, clinically considered to be
      squamous cell carcinoma. The growth was confined to the cervix and did not
      involve the parametria. However, on biopsy it was diagnosed as malignant
      melanoma. She underwent surgery elsewhere and was advised chemotherapy as these
      tumours are aggressive; however, she refused chemotherapy. She has been on
      regular follow-up and has an ongoing survival and disease-free period of more
      than 5 years. Primary cervical malignant melanomas are very rare as compared with
      vulval and vaginal counterparts and should be considered in the histological
      differential diagnosis of poorly differentiated malignant neoplasms involving
      cervix. Moreover, it is important to rule out metastasis from common primary
      sites such as skin, oesophagus, uveal tract and anorectal region before
      considering diagnosis of primary cervical melanoma.

PMID- 27895083
TI  - Locking plate external fixation and negative pressure wound therapy for treatment
      of a primary infection in a closed clavicle fracture.
AB  - Infection in a clavicle fracture is uncommon, but remains a challenging problem.
      A paucity of soft tissue coverage often combined with significant displacement
      and interfragmentary movement add complexity to an already difficult situation
      for effective infection treatment. External fixation in principle offers a means
      of achieving fracture stability, while the infection is being eradicated. We
      present the case of a closed clavicle fracture, initially treated conservatively,
      that presented 5 weeks later with infection. The fracture was definitively
      treated with external fixation using a locking plate positioned superficially to
      the skin, plus negative pressure wound therapy and subsequent secondary closure
      and antibiotic therapy. This case illustrates a novel method of treatment in this
      unusual presentation that was well tolerated by the patient and resulted in a
      good clinical outcome.

PMID- 27895082
TI  - VURD syndrome in an infant presenting with potentially fatal staphylococcal
      urinary tract infection and septicaemia.

PMID- 27895084
TI  - Prescription preferences in antipsychotics and attitude towards the
      pharmaceutical industry in Belgium.
AB  - OBJECTIVES: The number of antipsychotic prescriptions are increasing rapidly
      worldwide, a trend which is mainly driven by the steep rise in second-generation
      antipsychotic (SGA) prescriptions. However, the success of SGA, compared with the
      older first-generation antipsychotics (FGAs), cannot be explained by evidence.
      Several studies concluded on equal efficacy of FGA and SGA on positive, negative
      and cognitive symptoms of schizophrenia. Next to that, the influence of the
      pharmaceutical industry on prescription behaviour has drawn considerable
      interest. Therefore, the relationship between antipsychotic prescription patterns
      and exposure to information directly provided by pharmaceutical companies was
      studied. METHODS: A cross-sectional online survey, addressing psychiatrists,
      general practitioners (GPs) and trainees in Flanders, was carried out.
      Respondents were questioned about their prescription behaviour, opinion about
      efficacy of SGA versus FGA and the nature and frequency of their contact with the
      pharmaceutical industry. Using Spearman's rank correlations and chi2 tests, the
      relationship between different variables and group differences were examined.
      RESULTS: Psychiatrists, GPs and trainees in Flanders clearly favour olanzapine
      and risperidone, followed by quetiapine and aripiprazole above all other agents.
      This behaviour is supported by the conviction that SGAs have superior efficacy
      and a more benign side effect profile, compared with FGA. Frequent contact with
      drug representatives is correlated with a preference of SGA over FGA. 41% of the
      respondents acknowledge to be influenced by the pharmaceutical industry, which is
      more than that previously reported.

PMID- 27895085
TI  - Counterpoint: Potential Concerns Regarding the Use of Sex-Specific Cutpoints for
      High-Sensitivity Troponin Assays.

PMID- 27895086
TI  - Point: The Use of Sex-Specific Cutpoints for High-Sensitivity Cardiac Troponin
      Assays.

PMID- 27895087
TI  - Removing the waste bags: how p97 drives autophagy of lysosomes.

PMID- 27895088
TI  - Hormonal alterations in PCOS and its influence on bone metabolism.
AB  - According to the World Health Organization (WHO) polycystic ovary syndrome (PCOS)
      occurs in 4-8% of women worldwide. The prevalence of PCOS in Indian adolescents
      is 12.2% according to the Indian Council of Medical Research (ICMR). The National
      Institute of Health has documented that it affects approximately 5 million women
      of reproductive age in the United States. Hormonal imbalance is the
      characteristic of many women with polycystic ovarian syndrome (PCOS). The
      influence of various endocrine changes in PCOS women and their relevance to bone
      remains to be documented. Hormones, which include gonadotrophin-releasing hormone
      (GnRH), insulin, the leutinizing/follicle-stimulating hormone (LH/FSH) ratio,
      androgens, estrogens, growth hormones (GH), cortisol, parathyroid hormone (PTH)
      and calcitonin are disturbed in PCOS women. These hormones influence bone
      metabolism in human subjects directly as well as indirectly. The imbalance in
      these hormones results in increased prevalence of osteoporosis in PCOS women.
      Limited evidence suggests that the drugs taken during the treatment of PCOS
      increase the risk of bone fracture in PCOS patients through endocrine disruption.
      This review is aimed at the identification of the relationship between bone
      mineral density and hormonal changes in PCOS subjects and identifies potential
      areas to study bone-related disorders in PCOS women.

PMID- 27895091
TI  - The War on Women: And the Brave Ones Who Fight Back.

PMID- 27895089
TI  - Oxidized high density lipoprotein induces macrophage apoptosis via toll-like
      receptor 4-dependent CHOP pathway.
AB  - Oxidized HDL (ox-HDL), unlike native HDL that exerts antiatherogenic effects,
      plays a proatherogenic role. However, the underlying mechanisms are not
      completely understood. This study was designed to explore the inductive effect of
      ox-HDL on endoplasmic reticulum (ER) stress-CCAAT-enhancer-binding protein
      homologous protein (CHOP)-mediated macrophage apoptosis and its upstream
      mechanisms. Our results showed that ox-HDL could be ingested by macrophages,
      causing intracellular lipid accumulation. As with tunicamycin (an ER stress
      inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER
      stress pathway, including nuclear translocation of activating transcription
      factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic
      translation initiation factor 2alpha, and upregulation of glucose-regulated
      protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER
      stress inhibitor) and CHOP gene silencing. Additionally, diphenyleneiodonium
      (DPI, an oxidative stress inhibitor), probucol (a reactive oxygen species
      scavenger), and toll-like receptor 4 (TLR4) silencing reduced ox-HDL-induced
      macrophage apoptosis, oxidative stress, and CHOP upregulation. Moreover, HDL
      isolated from patients with metabolic syndrome induced macrophage apoptosis,
      oxidative stress, and CHOP upregulation, which were blocked by PBA and DPI. These
      data indicate that ox-HDL may activate ER stress-CHOP-induced apoptotic pathway
      in macrophages via enhanced oxidative stress and that this pathway may be
      mediated by TLR4.

PMID- 27895092
TI  - Characterization of Runella slithyformis HD-Pnk, a Bifunctional DNA/RNA End
      Healing Enzyme Composed of an N-Terminal 2',3'-Phosphoesterase HD Domain and a C
      Terminal 5'-OH Polynucleotide Kinase Domain.
AB  - 5'- and 3'-end-healing reactions are key steps in nucleic acid break repair in
      which 5'-OH ends are phosphorylated by a polynucleotide kinase (Pnk) and 3'-PO4
      or 2',3'-cyclic-PO4 ends are hydrolyzed by a phosphoesterase to generate the 5'
      PO4 and 3'-OH termini required for sealing by classic polynucleotide ligases. End
      healing and sealing enzymes are present in diverse bacterial taxa, often
      organized as modular units within a single multifunctional polypeptide or as
      subunits of a repair complex. Here we identify and characterize Runella
      slithyformis HD-Pnk as a novel bifunctional end-healing enzyme composed of an N
      terminal 2',3'-phosphoesterase HD domain and a C-terminal 5'-OH polynucleotide
      kinase P-loop domain. HD-Pnk phosphorylates 5'-OH polynucleotides (9-mers or
      longer) in the presence of magnesium and any nucleoside triphosphate donor. HD
      Pnk dephosphorylates RNA 2',3'-cyclic phosphate, RNA 3'-phosphate, RNA 2'
      phosphate, and DNA 3'-phosphate ends in the presence of a transition metal
      cofactor, which can be nickel, copper, or cobalt. HD-Pnk homologs are present in
      genera from 11 bacterial phyla and are often encoded in an operon with a putative
      ATP-dependent polynucleotide ligase. IMPORTANCE The present study provides
      insights regarding the diversity of nucleic acid repair strategies via the
      characterization of Runella slithyformis HD-Pnk as the exemplar of a novel clade
      of dual 5'- and 3'-end-healing enzymes that phosphorylate 5'-OH termini and
      dephosphorylate 2',3'-cyclic-PO4, 3'-PO4, and 2'-PO4 ends. The distinctive
      feature of HD-Pnk is its domain composition, i.e., a fusion of an N-terminal HD
      phosphohydrolase module and a C-terminal P-loop polynucleotide kinase module.
      Homologs of Runella HD-Pnk with the same domain composition, same domain order,
      and similar polypeptide sizes are distributed widely among genera from 11
      bacterial phyla.

PMID- 27895090
TI  - Identification of roles for H264, H306, H439, and H635 in acid-dependent
      lipoprotein release by the LDL receptor.
AB  - Lipoproteins internalized by the LDL receptor (LDLR) are released from this
      receptor in endosomes through a process that involves acid-dependent
      conformational changes in the receptor ectodomain. How acidic pH promotes this
      release process is not well understood. Here, we assessed roles for six histidine
      residues for which either genetic or structural data suggested a possible role in
      the acid-responsiveness of the LDLR. Using assays that measured conformational
      change, acid-dependent lipoprotein release, LDLR recycling, and net lipoprotein
      uptake, we show that H635 plays important roles in acid-dependent conformational
      change and lipoprotein release, while H264, H306, and H439 play ancillary roles
      in the response of the LDLR to acidic pH.

PMID- 27895093
TI  - Stroke paradox with SGLT-2 inhibitors: a play of chance or a viscosity-mediated
      reality?
AB  - Diabetes mellitus is a major risk factor for cardiovascular morbidity and
      mortality. Current therapeutic strategies have not provided constant beneficial
      cardiovascular-related results. Sodium-glucose co-transporters 2 (SGLT-2)
      inhibitors have emerged as a novel antidiabetic class of drugs that exert
      favourable results in a variety of other cardiovascular risk factors too, such as
      increased blood pressure and body weight. The Empagliflozin, Cardiovascular
      Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study was the first
      trial that evaluated cardiovascular outcomes in patients with diabetes with the
      use of empagliflozin, a member of this new class of drugs. Empagliflozin was
      associated with remarkable reduction of cardiovascular morbidity and mortality
      and all-cause death. On the contrary, stroke incidence was slightly increased,
      although the result did not reach statistical significance. It could be assumed
      that a drug providing such beneficial effects on cardiovascular outcomes, would
      have also the same impact in stroke risk. This finding could theoretically be
      attributed to 'play of chance'. However, an increase of haematocrit was observed
      in EMPA-REG and other SGLT-2 inhibitors studies. Accumulating evidence suggests a
      direct association between increased haematocrit and stroke risk. Could this
      'stroke paradox' be a result of the increased haematocrit levels noted with SGLT
      2 inhibitors? The aim of this review is to critically assess both possibilities,
      given that increased stroke rates (if indeed true) should not be neglected and
      unattended.

PMID- 27895094
TI  - Crosstalk between microRNA-122 and FOX family genes in HepG2 cells.
AB  - MicroRNA-122 (miR-122) is liver specific and plays an important role in
      physiology as well as diseases including hepatocellular carcinoma (HCC).
      Downregulation of miR-122 in HCC modulates apoptosis. Similarly, the putative
      targets of miR-122, the forkhead box (FOX) family genes also play an important
      role in the regulation of apoptosis. Hence, an interplay between miR-122 and FOX
      family genes has been explored in this study. Initially, an augmentation of
      apoptosis was noticed in HepG2 cells after transfection with miR-122. Further,
      the predicted miR-122 targets, the FOX family genes ( FOXM1b, FOXP1, and FOXO4)
      were selected via in silico analysis based on their role in apoptosis. We checked
      the expression of all these genes at transcript level after the transfection of
      miR-122 and found that the relative expression of FOXP1 and FOXM1b was
      significantly downregulated (p < 0.005) and that of FOXO4 was upregulated (p <
      0.005). Thus, the finding indicates deregulation of these FOX genes as a result
      of miR-122 augmentation might be involved in the modulation of apoptosis.

PMID- 27895096
TI  - ICRP and Radiological Protection in Medicine.
AB  - Standards in relation to radiological protection in medicine are well-documented,
      particularly with the recent update of the Basic Safety Standards. The principles
      of justification and optimisation remain key, as dose limitation is not
      applicable in medical practice. Appropriate justification relies on the
      knowledge, experience and discretion of the relevant medical practitioners and
      this may be overlooked in the race for diagnosis and treatment. One argument
      would be further regulation of medical exposures, although it is difficult to see
      how this could be imposed without denying patients essential investigations and
      treatments. Another contentious issue is individual patient dose management with
      the possible creation of a 'radiation passport'. Individual radiation
      susceptibility is a topic that has attracted much attention, but how to manage
      such persons, if identified, raises further questions. Communicating radiation
      risks and benefits to patients appropriately needs to be addressed, including who
      should be responsible for this, given accurate knowledge is a prerequisite.
      Ethics in radiological protection is also being widely discussed and this in
      relation to medical practice, which already involves numerous ethical issues, is
      likely to be open to debate in the near future.

PMID- 27895097
TI  - MASS MEDIA COMMUNICATION OF EMERGENCY ISSUES AND COUNTERMEASURES IN A NUCLEAR
      ACCIDENT: FUKUSHIMA REPORTING IN EUROPEAN NEWSPAPERS.
AB  - This paper presents the results of a large study of 1340 articles published by
      two major newspapers in six European countries (Belgium, Italy, Norway, Slovenia,
      Spain and Russia) in the first 2 months after the Fukushima Daiichi nuclear
      disaster. The focus of the analysis is on the application and overall impact of
      protective actions, both during the emergency phase and later, how the newspapers
      describe those actions, which differences were apparent between countries and
      what recommendations can be extracted in order to improve general communication
      about these issues. A clear lesson is that, even under uncertainty and
      recognising limitations, responsible authorities need to provide transparent,
      clear and understandable information to the public and the mass media right from
      the beginning of the early phase of any nuclear emergency. Clear, concise
      messages should be given. Mass media could play a key role in reassuring the
      public if the countermeasures are clearly explained.

PMID- 27895098
TI  - Brain aluminium accumulation and oxidative stress in the presence of calcium
      silicate dental cements.
AB  - Mineral trioxide aggregate (MTA) is a calcium silicate dental cement used for
      various applications in dentistry. This study was undertaken to test whether the
      presence of three commercial brands of calcium silicate dental cements in the
      dental extraction socket of rats would affect the brain aluminium (Al) levels and
      oxidative stress parameters. Right upper incisor was extracted and polyethylene
      tubes filled with MTA Angelus, MTA Fillapex or Theracal LC, or left empty for the
      control group, were inserted into the extraction socket. Rats were killed 7, 30
      or 60 days after operation. Brain tissues were obtained before killing. Al levels
      were measured by atomic absorption spectrometry. Thiobarbituric acid reactive
      substances (TBARS) levels, catalase (CAT), superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) activities were determined using spectrophotometry.
      A transient peak was observed in brain Al level of MTA Angelus group on day 7,
      while MTA Fillapex and Theracal LC groups reached highest brain Al level on day
      60. Brain TBARS level, CAT, SOD and GPx activities transiently increased on day 7
      and then returned to almost normal levels. This in vivo study for the first time
      indicated that initial washout may have occurred in MTA Angelus, while element
      leaching after the setting is complete may have taken place for MTA Fillapex and
      Theracal LC. Moreover, oxidative stress was induced and antioxidant enzymes were
      transiently upregulated. Further studies to search for oxidative neuronal damage
      should be done to completely understand the possible toxic effects of calcium
      silicate cements on the brain.

PMID- 27895095
TI  - Calprotectin in rheumatic diseases.
AB  - Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which
      are mainly produced by activated monocytes and neutrophils in the circulation and
      in inflamed tissues. The implication of calprotectin in the inflammatory process
      has already been demonstrated, but its role in the pathogenesis, diagnosis, and
      monitoring of rheumatic diseases has gained great attention in recent years.
      Calprotectin, being stable at room temperature, is a candidate biomarker for the
      follow-up of disease activity in many autoimmune disorders, where it can predict
      response to treatment or disease relapse. There is evidence that a number of
      immunomodulators, including TNF-alpha inhibitors, may reduce calprotectin
      expression. S100A8 and S100A9 have a potential role as a target of treatment in
      murine models of autoimmune disorders, since the direct or indirect blockade of
      these proteins results in amelioration of the disease process. In this review, we
      will go over the biologic functions of calprotectin which might be involved in
      the etiology of rheumatic disorders. We will also report evidence of its
      potential use as a disease biomarker. Impact statement Calprotectin is an acute
      phase protein produced by monocytes and neutrophils in the circulation and
      inflamed tissues. Calprotectin seems to be more sensitive than CRP, being able to
      detect minimal residual inflammation and is a candidate biomarker in inflammatory
      diseases. High serum levels are associated with some severe manifestations of
      rheumatic diseases, such as glomerulonephritis and lung fibrosis. Calprotectin
      levels in other fluids, such as saliva and synovial fluid, might be helpful in
      the diagnosis of rheumatic diseases. Of interest is also the potential role of
      calprotectin as a target of treatment.

PMID- 27895100
TI  - Virtual environments in cancer care: Pilot-testing a three-dimensional web-based
      platform as a tool for support in young cancer patients.
AB  - Bringing virtual environments into cancer support may offer a particular
      potential to engage patients and increase adherence to treatment. Developing and
      pilot-testing an online real-time multi-user three-dimensional platform, this
      study tested the use of an early prototype of the platform among adolescent and
      young adult cancer patients. Data were collected with an online questionnaire and
      using ethnographic methods of participant observation. The adolescent and young
      adult patients tested basic features of the virtual environment and some
      conducted brief in-world interactions with fellow patients during
      hospitalization. They had no reservations about using the technology and shared
      their ideas about its use. Our pilot test pointed to a number of areas of
      development for virtual environment applications as potential platforms for
      medical or behavioral interventions in cancer care. Overall, the results
      demonstrate the need for high user involvement in the development of such
      interventions and early testing of intervention designs.

PMID- 27895099
TI  - New thiazacridine agents: Synthesis, physical and chemical characterization, and
      in vitro anticancer evaluation.
AB  - A series of new thiazacridine agents were synthesized and evaluated as antitumor
      agents, in terms of not only their cytotoxicity but also their selectivity. The
      cytotoxicity assay confirmed that all compounds showed cytotoxic activity and
      selectivity. The new compound, 3-acridin-9-ylmethyl-5-(5-bromo-1 H-indol-3
      ylmethylene)-thiazolidine-2,4-dione (LPSF/AA29 - 7a), proved to be the most
      promising compound as it presents lower half-maximal inhibitory concentration
      (IC50) values (ranging from 0.25 to 68.03 uM) depending on cell lineage. In HepG2
      cells, the lowest IC50 value was exhibited by 3-acridin-9-ylmethyl-5-(4-piperidin
      1-yl-benzylidene)-thiazolidine-2,4-dione (LPSF/AA36 - 7b; 46.95 uM). None of the
      synthesized compounds showed cytotoxic activity against normal cells (IC50 > 100
      uM). The mechanism of death induction and cell cycle effects was also evaluated.
      Flow cytometric analysis revealed that the compounds LPSF/AA29 - 7a and LPSF/AA36
      - 7b significantly increased the percentage of apoptotic cells and induced G2/M
      arrest in the cell cycle progression. Therefore, these new thiazacridine
      derivatives constitute promising antitumor agents whose cytotoxicity and
      selectivity properties indicate they have potential to contribute to or serve as
      a basis for the development of new cancer drugs in the future.

PMID- 27895101
TI  - Interaction and common ground in dementia: Communication across linguistic and
      cultural diversity in a residential dementia care setting.
AB  - Previous research concerning bilingual people with a dementia disease has mainly
      focused on the importance of sharing a spoken language with caregivers. While
      acknowledging this, this article addresses the multidimensional character of
      communication and interaction. As using spoken language is made difficult as a
      consequence of the dementia disease, this multidimensionality becomes
      particularly important. The article is based on a qualitative analysis of
      ethnographic fieldwork at a dementia care facility. It presents ethnographic
      examples of different communicative forms, with particular focus on bilingual
      interactions. Interaction is understood as a collective and collaborative
      activity. The text finds that a shared spoken language is advantageous, but is
      not the only source of, nor a guarantee for, creating common ground and
      understanding. Communicative resources other than spoken language are for example
      body language, embodiment, artefacts and time. Furthermore, forms of
      communication are not static but develop, change and are created over time.
      Ability to communicate is thus not something that one has or has not, but is
      situationally and collaboratively created. To facilitate this, time and
      familiarity are central resources, and the results indicate the importance of
      continuity in interpersonal relations.

PMID- 27895102
TI  - Delaying and seeking care for obstructive sleep apnea: The role of gender,
      family, and morality.
AB  - Social scientists have proposed various theories as to when, why, and how people
      come to seek medical care for multiple conditions. Yet, there is still little
      empirical research to illustrate the pathways into and out of care, especially
      for chronic illness. This article contributes to this body of work by exploring
      individuals' reasons for delaying and seeking care for obstructive sleep apnea,
      which despite being the most diagnosed sleep disorder, has been largely neglected
      by social scientists. Drawing upon in-depth interviews with 65 Jewish-Israeli
      obstructive sleep apnea patients, this study shows how intersections of gender,
      family, and morality shape and are shaped by care-seeking behavior. The analysis
      reveals that married men claim they do not do health, thereby reaffirming their
      masculinity, but they maintain moral status because their wives do much of their
      illness work for them. Unmarried men, however, claim to be more vigilant in their
      pursuit of health and present it as one of their responsibilities. Women
      acknowledge they have the double burden of protecting their own health as well as
      that of their loved ones, and often feel that they are incapable of meeting these
      social expectations. However, men and women are able to maintain moral status by
      explaining their neglect of health as resulting from their attempts to care for
      significant others. Finally, married women differ from men and unmarried women in
      their motivations for seeking care. In keeping with their gender roles, married
      women emphasize disturbance to others whereas men stress disturbance to self.

PMID- 27895103
TI  - Impact of Donor Recipient Gender and Race Mismatch on Graft Outcomes in Patients
      With End-Stage Liver Disease Undergoing Liver Transplantation.
AB  - CONTEXT: The discrepancy between donor supply and organ demand increased the
      possibility of gender and race mismatch between the donors and recipients.
      However, the findings of their impact on graft and patient survival are outdated
      and mixed. OBJECTIVE: To estimate the effects of gender and race mismatch on
      graft survival and patient survival among adult patients (18 years and older)
      with end-stage liver disease. DESIGN: A total of 38 768 patients undergoing liver
      transplant between 2002 and 2011 were identified from United Network for Organ
      Sharing database. Kaplan-Meier curves, log-rank tests, and Cox proportional
      hazard regressions with backward elimination adopting a marginal approach with a
      working independence assumption and stratification on recipient hepatitis C virus
      status were used. MAIN OUTCOME MEASURES: Posttransplantation graft survival and
      patient survival. RESULTS: Both gender mismatch (hazard ratio [HR]: 1.14, 95%
      confidence interval [CI]: 1.09-1.12) and race mismatch (HR 1.08, 95%C: 1.04-1.12)
      had significantly adverse effects on graft survival and patient survival after
      controlling for other factors, especially among hepatitis C-positive female
      recipients with male donors (HR 1.13, 95%CI 1.03-1.24), black recipients with
      white donors (1.39, 1.29-1.49) or Hispanic donors (HR 1.48, 95%CI 1.27-1.72), and
      these effects were even worse among hepatitis C-positive recipients. CONCLUSION:
      Gender and race mismatch between donors and recipients adversely affected graft
      survival and patient survival among adult patients with end-stage liver disease,
      both independently and after the adjustment for other factors. Future research is
      recommended to explore other factors such as new model for end-stage liver
      disease sharing policy change and disparities in access to waiting-list or
      transplantation.

PMID- 27895104
TI  - Bin1 and CD2AP polarise the endocytic generation of beta-amyloid.
AB  - The mechanisms driving pathological beta-amyloid (Abeta) generation in late-onset
      Alzheimer's disease (AD) are unclear. Two late-onset AD risk factors, Bin1 and
      CD2AP, are regulators of endocytic trafficking, but it is unclear how their
      endocytic function regulates Abeta generation in neurons. We identify a novel
      neuron-specific polarisation of Abeta generation controlled by Bin1 and CD2AP We
      discover that Bin1 and CD2AP control Abeta generation in axonal and dendritic
      early endosomes, respectively. Both Bin1 loss of function and CD2AP loss of
      function raise Abeta generation by increasing APP and BACE1 convergence in early
      endosomes, however via distinct sorting events. When Bin1 levels are reduced,
      BACE1 is trapped in tubules of early endosomes and fails to recycle in axons.
      When CD2AP levels are reduced, APP is trapped at the limiting membrane of early
      endosomes and fails to be sorted for degradation in dendrites. Hence, Bin1 and
      CD2AP keep APP and BACE1 apart in early endosomes by distinct mechanisms in axon
      and dendrites. Individuals carrying variants of either factor would slowly
      accumulate Abeta in neurons increasing the risk for late-onset AD.

PMID- 27895106
TI  - Saliva exosomes from pancreatic tumor-bearing mice modulate NK cell phenotype and
      antitumor cytotoxicity.
AB  - Tumor exosomes are emerging as antitumor immunity regulators; however, their
      effects on secondary exosome secretion by distal organs have not been explored.
      We have previously demonstrated that suppression of exosomes at the distal tumor
      site of pancreatic ductal adenocarcinoma (PDAC) ablated the development of
      salivary biomarker profile. Here, we explore the function of salivary exosomes
      from tumor-bearing mice in immune surveillance. We provide evidence that salivary
      exosomes from mice with PDAC exhibit a suppressive effect that results in reduced
      tumor-killing capacity by NK cells. Salivary exosomes from mice with PDAC where
      pancreatic tumors were engineered to suppress exosome biogenesis failed to
      suppress NK cell cytotoxic potential against tumor cells, as opposed to salivary
      exosomes from mice with PDAC with normal tumor exosome biogenesis. These results
      reveal an important and previously unknown mechanism of antitumor immune
      regulation and provide new insights into our understanding of the alterations of
      this biofluid during tumor development.-Katsiougiannis, S., Chia, D., Kim, Y.,
      Singh, R. P., Wong, D. T. W. Saliva exosomes from pancreatic tumor-bearing mice
      modulate NK cell phenotype and antitumor cytotoxicity.

PMID- 27895107
TI  - Long noncoding RNA H19 accelerates tenogenic differentiation and promotes tendon
      healing through targeting miR-29b-3p and activating TGF-beta1 signaling.
AB  - Tendon injures are common orthopedic conditions, but tendon development and the
      pathogenesis of tendon injures, such as tendinopathy, remain largely unknown and
      have limited the development of clinical therapy. Studies on tenogenic
      differentiation at the molecular level may help in developing novel therapeutic
      strategies. As novel regulators, long noncoding RNAs (lncRNAs) have been found to
      have widespread biological functions, and emerging evidence demonstrates that
      lncRNAs may play important regulatory roles in cell differentiation and tissue
      regeneration. In this study, we found that lncRNA H19 stimulated tenogenesis of
      human tendon-derived stem cells. Stable overexpression of H19 significantly
      accelerated TGF-beta1-induced tenogenic differentiation in vitro and accelerated
      tendon healing in a mouse tendon defect model. H19 directly targeted miR-29b-3p,
      which is considered to be a negative regulator of tenogenesis. Furthermore, miR
      29b-3p directly suppressed the expression of TGF-beta1 and type I collagen,
      thereby forming a novel regulatory feedback loop between H19 and TGF-beta1 to
      mediate tenogenic differentiation. Our study demonstrated that H19 promotes
      tenogenic differentiation both in vitro and in vivo by targeting miR-29b-3p and
      activating TGF-beta1 signaling. Regulation of the TGF-beta1/H19/miR-29b-3p
      regulatory loop may be a new strategy for treating tendon injury.-Lu, Y.-F., Liu,
      Y., Fu, W.-M., Xu, J., Wang, B., Sun, Y.-X., Wu, T.-Y., Xu, L.-L, Chan, K.-M.,
      Zhang, J.-F., Li, G. Long noncoding RNA H19 accelerates tenogenic differentiation
      and promotes tendon healing through targeting miR-29b-3p and activating TGF-beta1
      signaling.

PMID- 27895105
TI  - Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle
      injury.
AB  - The efficacy and optimization of poststroke physical therapy paradigms is
      challenged in part by a lack of objective tools available to researchers for
      systematic preclinical testing. This work represents a maiden effort to develop a
      robot-assisted mechanical therapy (RAMT) device to objectively address the
      significance of mechanical physiotherapy on poststroke outcomes. Wistar rats were
      subjected to right hemisphere middle-cerebral artery occlusion and reperfusion.
      After 24 h, rats were split into control (RAMT-) or RAMT+ groups (30 min daily
      RAMT over the stroke-affected gastrocnemius) and were followed up to poststroke d
      14. RAMT+ increased perfusion 1.5-fold in stroke-affected gastrocnemius as
      compared to RAMT- controls. Furthermore, RAMT+ rats demonstrated improved
      poststroke track width (11% wider), stride length (21% longer), and travel
      distance (61% greater), as objectively measured using software-automated testing
      platforms. Stroke injury acutely increased myostatin (3-fold) and lowered brain
      derived neurotrophic factor (BDNF) expression (0.6-fold) in the stroke-affected
      gastrocnemius, as compared to the contralateral one. RAMT attenuated the stroke
      induced increase in myostatin and increased BDNF expression in skeletal muscle.
      Additional RAMT-sensitive myokine targets in skeletal muscle (IL-1ra and IP
      10/CXCL10) were identified from a cytokine array. Taken together, outcomes
      suggest stroke acutely influences signal transduction in hindlimb skeletal
      muscle. Regimens based on mechanical therapy have the clear potential to protect
      hindlimb function from such adverse influence.-Sen, C. K., Khanna, S., Harris,
      H., Stewart, R., Balch, M., Heigel, M., Teplitsky, S., Gnyawali, S., Rink, C.
      Robot-assisted mechanical therapy attenuates stroke-induced limb skeletal muscle
      injury.

PMID- 27895108
TI  - The effect of dietary fish oil on weight gain and insulin sensitivity is
      dependent on APOE genotype in humanized targeted replacement mice.
AB  - We investigated the independent and interactive impact of the common APOE
      genotype and marine n-3 polyunsaturated fatty acids (PUFAs) on the development of
      obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3
      and APOE4 targeted replacement mice were fed either a control high-fat diet (HFD)
      or an HFD supplemented with 3% n-3 PUFAs from fish oil (HFD + FO) for 8 wk. We
      established the impact of intervention on food intake, body weight, and visceral
      adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver
      enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose
      tolerance test; and Glut4 and ApoE expression in VAT. HFD feeding induced more
      weight gain and higher plasma lipids in APOE3 compared to APOE4 mice (P < 0.05),
      along with a 2-fold higher insulin and impaired glucose tolerance. Supplementing
      APOE3, but not APOE4, animals with dietary n-3 PUFAs decreased body-weight gain,
      plasma lipids, and insulin (P < 0.05) and improved glucose tolerance, which was
      associated with increased VAT Glut4 mRNA levels (P < 0.05). Our findings
      demonstrate that an APOE3 genotype predisposes mice to develop obesity and its
      metabolic complications, which was attenuated by n-3 PUFA supplementation.-Slim,
      K. E., Vauzour, D., Tejera, N., Voshol, P. J., Cassidy, A., Minihane, A. M. The
      effect of dietary fish oil on weight gain and insulin sensitivity is dependent on
      APOE genotype in humanized targeted replacement mice.

PMID- 27895109
TI  - Enhancers and super-enhancers have an equivalent regulatory role in embryonic
      stem cells through regulation of single or multiple genes.
AB  - Transcriptional enhancers are critical for maintaining cell-type-specific gene
      expression and driving cell fate changes during development. Highly transcribed
      genes are often associated with a cluster of individual enhancers such as those
      found in locus control regions. Recently, these have been termed stretch
      enhancers or super-enhancers, which have been predicted to regulate critical cell
      identity genes. We employed a CRISPR/Cas9-mediated deletion approach to study the
      function of several enhancer clusters (ECs) and isolated enhancers in mouse
      embryonic stem (ES) cells. Our results reveal that the effect of deleting ECs,
      also classified as ES cell super-enhancers, is highly variable, resulting in
      target gene expression reductions ranging from 12% to as much as 92%. Partial
      deletions of these ECs which removed only one enhancer or a subcluster of
      enhancers revealed partially redundant control of the regulated gene by multiple
      enhancers within the larger cluster. Many highly transcribed genes in ES cells
      are not associated with a super-enhancer; furthermore, super-enhancer predictions
      ignore 81% of the potentially active regulatory elements predicted by cobinding
      of five or more pluripotency-associated transcription factors. Deletion of these
      additional enhancer regions revealed their robust regulatory role in gene
      transcription. In addition, select super-enhancers and enhancers were identified
      that regulated clusters of paralogous genes. We conclude that, whereas robust
      transcriptional output can be achieved by an isolated enhancer, clusters of
      enhancers acting on a common target gene act in a partially redundant manner to
      fine tune transcriptional output of their target genes.

PMID- 27895110
TI  - Nucleosome occupancy as a novel chromatin parameter for replication origin
      functions.
AB  - Eukaryotic DNA replication initiates from multiple discrete sites in the genome,
      termed origins of replication (origins). Prior to S phase, multiple origins are
      poised to initiate replication by recruitment of the pre-replicative complex (pre
      RC). For proper replication to occur, origin activation must be tightly
      regulated. At the population level, each origin has a distinct firing time and
      frequency of activation within S phase. Many studies have shown that chromatin
      can strongly influence initiation of DNA replication. However, the chromatin
      parameters that affect properties of origins have not been thoroughly
      established. We found that nucleosome occupancy in G1 varies greatly around
      origins across the S. cerevisiae genome, and nucleosome occupancy around origins
      significantly correlates with the activation time and efficiency of origins, as
      well as pre-RC formation. We further demonstrate that nucleosome occupancy around
      origins in G1 is established during transition from G2/M to G1 in a pre-RC
      dependent manner. Importantly, the diminished cell-cycle changes in nucleosome
      occupancy around origins in the orc1-161 mutant are associated with an abnormal
      global origin usage profile, suggesting that proper establishment of nucleosome
      occupancy around origins is a critical step for regulation of global origin
      activities. Our work thus establishes nucleosome occupancy as a novel and key
      chromatin parameter for proper origin regulation.

PMID- 27895112
TI  - Hepatic Dipeptidyl Peptidase-4 Controls Pharmacokinetics of Vildagliptin In Vivo.
AB  - The main route of elimination of vildagliptin, which is an inhibitor of
      dipeptidyl peptidase-4 (DPP-4), in humans is cyano group hydrolysis to produce a
      carboxylic acid metabolite M20.7. Our in vitro study previously demonstrated that
      DPP-4 itself greatly contributed to the hydrolysis of vildagliptin in mouse, rat,
      and human livers. To investigate whether hepatic DPP-4 contributes to the
      hydrolysis of vildagliptin in vivo, in the present study, we conducted in vivo
      pharmacokinetics studies of vildagliptin in mice coadministered with vildagliptin
      and sitagliptin, which is another DPP-4 inhibitor, and also in streptozotocin
      (STZ)-induced diabetic mice. The area under the plasma concentration-time curve
      (AUC) value of M20.7 in mice coadministered with vildagliptin and sitagliptin was
      significantly lower than that in mice administered vildagliptin alone (P < 0.01).
      Although plasma DPP-4 expression level was increased 1.9-fold, hepatic DPP-4
      activity was decreased in STZ-induced diabetic mice. The AUC values of M20.7 in
      STZ-induced diabetic mice were lower than those in control mice (P < 0.01).
      Additionally, the AUC values of M20.7 significantly positively correlated with
      hepatic DPP-4 activities in the individual mice (Rs = 0.943, P < 0.05). These
      findings indicated that DPP-4 greatly contributed to the hydrolysis of
      vildagliptin in vivo and that not plasma, but hepatic DPP-4 controlled
      pharmacokinetics of vildagliptin. Furthermore, enzyme assays of 23 individual
      human liver samples showed that there was a 3.6-fold interindividual variability
      in vildagliptin-hydrolyzing activities. Predetermination of the interindividual
      variability of hepatic vildagliptin-hydrolyzing activity might be useful for the
      prediction of blood vildagliptin concentrations in vivo.

PMID- 27895111
TI  - Discovery and genotyping of structural variation from long-read haploid genome
      sequence data.
AB  - In an effort to more fully understand the full spectrum of human genetic
      variation, we generated deep single-molecule, real-time (SMRT) sequencing data
      from two haploid human genomes. By using an assembly-based approach (SMRT-SV), we
      systematically assessed each genome independently for structural variants (SVs)
      and indels resolving the sequence structure of 461,553 genetic variants from 2 bp
      to 28 kbp in length. We find that >89% of these variants have been missed as part
      of analysis of the 1000 Genomes Project even after adjusting for more common
      variants (MAF > 1%). We estimate that this theoretical human diploid differs by
      as much as ~16 Mbp with respect to the human reference, with long-read sequencing
      data providing a fivefold increase in sensitivity for genetic variants ranging in
      size from 7 bp to 1 kbp compared with short-read sequence data. Although a large
      fraction of genetic variants were not detected by short-read approaches, once the
      alternate allele is sequence-resolved, we show that 61% of SVs can be genotyped
      in short-read sequence data sets with high accuracy. Uncoupling discovery from
      genotyping thus allows for the majority of this missed common variation to be
      genotyped in the human population. Interestingly, when we repeat SV detection on
      a pseudodiploid genome constructed in silico by merging the two haploids, we find
      that ~59% of the heterozygous SVs are no longer detected by SMRT-SV. These
      results indicate that haploid resolution of long-read sequencing data will
      significantly increase sensitivity of SV detection.

PMID- 27895113
TI  - Age-Dependent Absolute Abundance of Hepatic Carboxylesterases (CES1 and CES2) by
      LC-MS/MS Proteomics: Application to PBPK Modeling of Oseltamivir In Vivo
      Pharmacokinetics in Infants.
AB  - The age-dependent absolute protein abundance of carboxylesterase (CES) 1 and CES2
      in human liver was investigated and applied to predict infant pharmacokinetics
      (PK) of oseltamivir. The CES absolute protein abundance was determined by liquid
      chromatography-tandem mass spectrometry proteomics in human liver microsomal and
      cytosolic fractions prepared from tissue samples obtained from 136 pediatric
      donors and 35 adult donors. Two surrogate peptides per protein were selected for
      the quantification of CES1 and CES2 protein abundance. Purified CES1 and CES2
      protein standards were used as calibrators, and the heavy labeled peptides were
      used as the internal standards. In hepatic microsomes, CES1 and CES2 abundance
      (in picomoles per milligram total protein) increased approximately 5-fold (315.2
      vs. 1664.4) and approximately 3-fold (59.8 vs. 174.1) from neonates to adults,
      respectively. CES1 protein abundance in liver cytosol also showed age-dependent
      maturation. Oseltamivir carboxylase activity was correlated with protein
      abundance in pediatric and adult liver microsomes. The protein abundance data
      were then used to model in vivo PK of oseltamivir in infants using pediatric
      physiologically based PK modeling and incorporating the protein abundance-based
      ontogeny function into the existing pediatric Simcyp model. The predicted
      pediatric area under the curve, maximal plasma concentration, and time for
      maximal plasma concentration values were below 2.1-fold of the clinically
      observed values, respectively.

PMID- 27895114
TI  - In Vitro and Clinical Evaluations of the Drug-Drug Interaction Potential of a
      Metabotropic Glutamate 2/3 Receptor Agonist Prodrug with Intestinal Peptide
      Transporter 1.
AB  - Despite peptide transporter 1 (PEPT1) being responsible for the bioavailability
      for a variety of drugs, there has been little study of its potential involvement
      in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3
      receptor agonist prodrug, utilizes PEPT1 to enhance absorption and
      bioavailability. In vitro studies were conducted to guide the decision to conduct
      a clinical drug interaction study and to inform the clinical study design. In
      vitro investigations determined the prodrug (LY2140023 monohydrate) is a
      substrate of PEPT1 with Km value of approximately 30 uM, whereas the active
      moiety (LY404039) is not a PEPT1 substrate. In addition, among the eight known
      PEPT1 substrates evaluated in vitro, valacyclovir was the most potent inhibitor
      (IC50 = 0.46 mM) of PEPT1-mediated uptake of the prodrug. Therefore, a clinical
      drug interaction study was conducted to evaluate the potential interaction
      between the prodrug and valacyclovir in healthy subjects. No effect of
      coadministration was observed on the pharmacokinetics of the prodrug,
      valacyclovir, or either of their active moieties. Although in vitro studies
      showed potential for the prodrug and valacyclovir interaction via PEPT1, an in
      vivo study showed no interaction between these two drugs. PEPT1 does not appear
      to easily saturate because of its high capacity and expression in the intestine.
      Thus, a clinical interaction at PEPT1 is unlikely even with a compound with high
      affinity for the transporter.

PMID- 27895116
TI  - Correctors and Potentiators Rescue Function of the Truncated W1282X-Cystic
      Fibrosis Transmembrane Regulator (CFTR) Translation Product.
AB  - W1282X is the fifth most common cystic fibrosis transmembrane regulator (CFTR)
      mutation that causes cystic fibrosis. Here, we investigated the utility of a
      small molecule corrector/potentiator strategy, as used for DeltaF508-CFTR, to
      produce functional rescue of the truncated translation product of the W1282X
      mutation, CFTR1281, without the need for read-through. In transfected cell
      systems, certain potentiators and correctors, including VX-809 and VX-770,
      increased CFTR1281 activity. To identify novel correctors and potentiators with
      potentially greater efficacy on CFTR1281, functional screens were done of ~30,000
      synthetic small molecules and drugs/nutraceuticals in CFTR1281-transfected cells.
      Corrector scaffolds of 1-arylpyrazole-4-arylsulfonyl-piperazine and spiro
      piperidine-quinazolinone classes were identified with up to ~5-fold greater
      efficacy than VX-809, some of which were selective for CFTR1281, whereas others
      also corrected DeltaF508-CFTR. Several novel potentiator scaffolds were
      identified with efficacy comparable with VX-770; remarkably, a phenylsulfonamide
      pyrrolopyridine acted synergistically with VX-770 to increase CFTR1281 function
      ~8-fold over that of VX-770 alone, normalizing CFTR1281 channel activity to that
      of wild type CFTR. Corrector and potentiator combinations were tested in primary
      cultures and conditionally reprogrammed cells generated from nasal brushings from
      one W1282X homozygous subject. Although robust chloride conductance was seen with
      correctors and potentiators in homozygous DeltaF508 cells, increased chloride
      conductance was not found in W1282X cells despite the presence of adequate
      transcript levels. Notwithstanding the negative data in W1282X cells from one
      human subject, we speculate that corrector and potentiator combinations may have
      therapeutic efficacy in cystic fibrosis caused by the W1282X mutation, although
      additional studies are needed on human cells from W1282X subjects.

PMID- 27895115
TI  - Shared Subunits of Tetrahymena Telomerase Holoenzyme and Replication Protein A
      Have Different Functions in Different Cellular Complexes.
AB  - In most eukaryotes, telomere maintenance relies on telomeric repeat synthesis by
      a reverse transcriptase named telomerase. To synthesize telomeric repeats, the
      catalytic subunit telomerase reverse transcriptase (TERT) uses the RNA subunit
      (TER) as a template. In the ciliate Tetrahymena thermophila, the telomerase
      holoenzyme consists of TER, TERT, and eight additional proteins, including the
      telomeric repeat single-stranded DNA-binding protein Teb1 and its heterotrimer
      partners Teb2 and Teb3. Teb1 is paralogous to the large subunit of the general
      single-stranded DNA binding heterotrimer replication protein A (RPA). Little is
      known about the function of Teb2 and Teb3, which are structurally homologous to
      the RPA middle and small subunits, respectively. Here, epitope-tagging Teb2 and
      Teb3 expressed at their endogenous gene loci enabled affinity purifications that
      revealed that, unlike other Tetrahymena telomerase holoenzyme subunits, Teb2 and
      Teb3 are not telomerase-specific. Teb2 and Teb3 assembled into other heterotrimer
      complexes, which when recombinantly expressed had the general single-stranded DNA
      binding activity of RPA complexes, unlike the telomere-specific DNA binding of
      Teb1 or the TEB heterotrimer of Teb1, Teb2, and Teb3. TEB had no more DNA binding
      affinity than Teb1 alone. In contrast, heterotrimers reconstituted with Teb2 and
      Teb3 and two other Tetrahymena RPA large subunit paralogs had higher DNA binding
      affinity than their large subunit alone. Teb1 and TEB, but not RPA, increased
      telomerase processivity. We conclude that in the telomerase holoenzyme, instead
      of binding DNA, Teb2 and Teb3 are Teb1 assembly factors. These findings
      demonstrate that Tetrahymena telomerase holoenzyme and RPA complexes share
      subunits and that RPA subunits have distinct functions in different heterotrimer
      assemblies.

PMID- 27895117
TI  - Examining Crosstalk among Transforming Growth Factor beta, Bone Morphogenetic
      Protein, and Wnt Pathways.
AB  - The integration of morphogenic signals by cells is not well understood. A growing
      body of literature suggests increasingly complex coupling among classically
      defined pathways. Given this apparent complexity, it is difficult to predict
      where, when, or even whether crosstalk occurs. Here, we investigated pairs of
      morphogenic pathways, previously reported to have multiple points of crosstalk,
      which either do not share (TGFbeta and Wnt/beta-catenin) or share (TGFbeta and
      bone morphogenetic protein (BMP)) core signaling components. Crosstalk was
      measured by the ability of one morphogenic pathway to cross-activate core
      transcription factors and/or target genes of another morphogenic pathway. In
      contrast to previous studies, we found a surprising absence of crosstalk between
      TGFbeta and Wnt/beta-catenin. Further, we did not observe expected cross-pathway
      inhibition in between TGFbeta and BMP, despite the fact that both use (or could
      compete) for the shared component SMAD4. Critical to our assays was a separation
      of timescales, which helped separate crosstalk due to initial signal transduction
      from subsequent post-transcriptional feedback events. Our study revealed fewer
      (and different) inter-morphogenic pathway crosstalk connections than expected;
      even pathways that share components can be insulated from one another.

PMID- 27895118
TI  - Co-evolution of Two GTPases Enables Efficient Protein Targeting in an RNA-less
      Chloroplast Signal Recognition Particle Pathway.
AB  - The signal recognition particle (SRP) is an essential ribonucleoprotein particle
      that mediates the co-translational targeting of newly synthesized proteins to
      cellular membranes. The SRP RNA is a universally conserved component of SRP that
      mediates key interactions between two GTPases in SRP and its receptor, thus
      enabling rapid delivery of cargo to the target membrane. Notably, this essential
      RNA is bypassed in the chloroplast (cp) SRP of green plants. Previously, we
      showed that the cpSRP and cpSRP receptor GTPases (cpSRP54 and cpFtsY,
      respectively) interact efficiently by themselves without the SRP RNA. Here, we
      explore the molecular mechanism by which this is accomplished. Fluorescence
      analyses showed that, in the absence of SRP RNA, the M-domain of cpSRP54 both
      accelerates and stabilizes complex assembly between cpSRP54 and cpFtsY. Cross
      linking coupled with mass spectrometry and mutational analyses identified a new
      interaction between complementarily charged residues on the cpFtsY G-domain and
      the vicinity of the cpSRP54 M-domain. These residues are specifically conserved
      in plastids, and their evolution coincides with the loss of SRP RNA in green
      plants. These results provide an example of how proteins replace the functions of
      RNA during evolution.

PMID- 27895119
TI  - Partial Agonist and Biased Signaling Properties of the Synthetic Enantiomers
      J113863/UCB35625 at Chemokine Receptors CCR2 and CCR5.
AB  - Biased agonism at G protein-coupled receptors constitutes a promising area of
      research for the identification of new therapeutic molecules. In this study we
      identified two novel biased ligands for the chemokine receptors CCR2 and CCR5 and
      characterized their functional properties. We showed that J113863 and its
      enantiomer UCB35625, initially identified as high affinity antagonists for CCR1
      and CCR3, also bind with low affinity to the closely related receptors CCR2 and
      CCR5. Binding of J113863 and UCB35625 to CCR2 or CCR5 resulted in the full or
      partial activation of the three Gi proteins and the two Go isoforms. Unlike
      chemokines, the compounds did not activate G12 Binding of J113863 to CCR2 or CCR5
      also induced the recruitment of beta-arrestin 2, whereas UCB35625 did not.
      UCB35625 induced the chemotaxis of L1.2 cells expressing CCR2 or CCR5. In
      contrast, J113863 induced the migration of L1.2-CCR2 cells but antagonized the
      chemokine-induced migration of L1.2-CCR5 cells. We also showed that replacing the
      phenylalanine 3.33 in CCR5 TM3 by the corresponding histidine of CCR2 converts
      J113863 from an antagonist for cell migration and a partial agonist in other
      assays to a full agonist in all assays. Further analyses indicated that F3.33H
      substitution strongly increased the activation of G proteins and beta-arrestin 2
      by J113863. These results highlight the biased nature of the J113863 and UCB35625
      that act either as antagonist, partial agonist, or full agonist according to the
      receptor, the enantiomer, and the signaling pathway investigated.

PMID- 27895120
TI  - Ankyrin G Expression Regulates Apical Delivery of the Epithelial Sodium Channel
      (ENaC).
AB  - The epithelial sodium channel (ENaC) is the limiting entry point for Na+
      reabsorption in the distal kidney nephron and is regulated by numerous hormones,
      including the mineralocorticoid hormone aldosterone. Previously we identified
      ankyrin G (AnkG), a cytoskeletal protein involved in vesicular transport, as a
      novel aldosterone-induced protein that can alter Na+ transport in mouse cortical
      collecting duct cells. However, the mechanisms underlying AnkG regulation of Na+
      transport were unknown. Here we report that AnkG expression directly regulates
      Na+ transport by altering ENaC activity in the apical membrane. Increasing AnkG
      expression increased ENaC activity while depleting AnkG reduced ENaC-mediated Na+
      transport. These changes were due to a change in ENaC directly rather than
      through alterations to the Na+ driving force created by Na+/K+-ATPase. Using a
      constitutively open mutant of ENaC, we demonstrate that the augmentation of Na+
      transport is caused predominantly by increasing the number of ENaCs at the
      surface. To determine the mechanism of AnkG action on ENaC surface number,
      changes in rates of internalization, recycling, and membrane delivery were
      investigated. AnkG did not alter ENaC delivery to the membrane from biosynthetic
      pathways or removal by endocytosis. However, AnkG did alter ENaC insertion from
      constitutive recycling pathways. These findings provide a mechanism to account
      for the role of AnkG in the regulation of Na+ transport in the distal kidney
      nephron.

PMID- 27895121
TI  - Neuronal mTORC1 Is Required for Maintaining the Nonreactive State of Astrocytes.
AB  - Astrocytes respond to CNS insults through reactive astrogliosis, but the
      underlying mechanisms are unclear. In this study, we show that inactivation of
      mechanistic target of rapamycin complex (mTORC1) signaling in postnatal neurons
      induces reactive astrogliosis in mice. Ablation of Raptor (an mTORC1-specific
      component) in postmitotic neurons abolished mTORC1 activity and produced neurons
      with smaller soma and fewer dendrites, resulting in microcephaly and aberrant
      behavior in adult mice. Interestingly, extensive astrogliosis without significant
      astrocyte proliferation and glial scar formation was observed in these mice. The
      inhibition of neuronal mTORC1 may activate astrogliosis by reducing neuron
      derived fibroblast growth factor 2 (FGF-2), which might trigger FGF receptor
      signaling in astrocytes to maintain their nonreactive state, and FGF-2 injection
      successfully prevented astrogliosis in Raptor knock-out mice. This study
      demonstrates that neuronal mTORC1 inhibits reactive astrogliosis and plays an
      important role in CNS pathologies.

PMID- 27895122
TI  - Reciprocal Regulation of Target of Rapamycin Complex 1 and Potassium
      Accumulation.
AB  - The proper maintenance of potassium homeostasis is crucial for cell viability.
      Among the major determinants of potassium uptake in the model organism
      Saccharomyces cerevisiae are the Trk1 high affinity potassium transporter and the
      functionally redundant Hal4 (Sat4) and Hal5 protein kinases. These kinases are
      required for the plasma membrane accumulation of not only Trk1 but also several
      nutrient permeases. Here, we show that overexpression of the target of rapamycin
      complex 1 (TORC1) effector NPR1 improves hal4 hal5 growth defects by stabilizing
      nutrient permeases at the plasma membrane. We subsequently found that internal
      potassium levels and TORC1 activity are linked. Specifically, growth under
      limiting potassium alters the activities of Npr1 and another TORC1 effector
      kinase, Sch9; hal4 hal5 and trk1 trk2 mutants display hypersensitivity to
      rapamycin, and reciprocally, TORC1 inhibition reduces potassium accumulation. Our
      results demonstrate that in addition to carbon and nitrogen, TORC1 also responds
      to and regulates potassium fluxes.

PMID- 27895123
TI  - Addressing the Functional Determinants of FAK during Ciliogenesis in
      Multiciliated Cells.
AB  - We previously identified focal adhesion kinase (FAK) as an important regulator of
      ciliogenesis in multiciliated cells. FAK and other focal adhesion (FA) proteins
      associate with the basal bodies and their striated rootlets and form complexes
      named ciliary adhesions (CAs). CAs display similarities with FAs but are
      established in an integrin independent fashion and are responsible for anchoring
      basal bodies to the actin cytoskeleton during ciliogenesis as well as in mature
      multiciliated cells. FAK down-regulation leads to aberrant ciliogenesis due to
      impaired association between the basal bodies and the actin cytoskeleton,
      suggesting that FAK is an important regulator of the CA complex. However, the
      mechanism through which FAK functions in the complex is not clear, and in this
      study we examined the role of this protein in both ciliogenesis and ciliary
      function. We show that localization of FAK at CAs depends on interactions taking
      place at the amino-terminal (FERM) and carboxyl-terminal (FAT) domains and that
      both domains are required for proper ciliogenesis and ciliary function.
      Furthermore, we show that an interaction with another CA protein, paxillin, is
      essential for correct localization of FAK in multiciliated cells. This
      interaction is indispensable for both ciliogenesis and ciliary function. Finally,
      we provide evidence that despite the fact that FAK is in the active, open
      conformation at CAs, its kinase activity is dispensable for ciliogenesis and
      ciliary function revealing that FAK plays a scaffolding role in multiciliated
      cells. Overall these data show that the role of FAK at CAs displays similarities
      but also important differences compared with its role at FAs.

PMID- 27895124
TI  - Anionic Phospholipids and the Albino3 Translocase Activate Signal Recognition
      Particle-Receptor Interaction during Light-harvesting Chlorophyll a/b-binding
      Protein Targeting.
AB  - The universally conserved signal recognition particle (SRP) co-translationally
      delivers newly synthesized membrane and secretory proteins to the target cellular
      membrane. The only exception is found in the chloroplast of green plants, where
      the chloroplast SRP (cpSRP) post-translationally targets light-harvesting
      chlorophyll a/b-binding proteins (LHCP) to the thylakoid membrane. The mechanism
      and regulation of this post-translational mode of targeting by cpSRP remain
      unclear. Using biochemical and biophysical methods, here we show that anionic
      phospholipids activate the cpSRP receptor cpFtsY to promote rapid and stable
      cpSRP54.cpFtsY complex assembly. Furthermore, the stromal domain of the Alb3
      translocase binds with high affinity to and regulates GTP hydrolysis in the
      cpSRP54.cpFtsY complex, suggesting that cpFtsY is primarily responsible for
      initial recruitment of the targeting complex to Alb3. These results suggest a new
      model for the sequential recruitment, remodeling, and unloading of the targeting
      complex at membrane translocase sites in the post-translational cpSRP pathway.

PMID- 27895125
TI  - Lineage-specific SoxR-mediated Regulation of an Endoribonuclease Protects Non
      enteric Bacteria from Redox-active Compounds.
AB  - Bacteria use redox-sensitive transcription factors to coordinate responses to
      redox stress. The [2Fe-2S] cluster-containing transcription factor SoxR is
      particularly tuned to protect cells against redox-active compounds (RACs). In
      enteric bacteria, SoxR is paired with a second transcription factor, SoxS, that
      activates downstream effectors. However, SoxS is absent in non-enteric bacteria,
      raising questions as to how SoxR functions. Here, we first show that SoxR of
      Acinetobacter oleivorans displayed similar activation profiles in response to
      RACs as did its homolog from Escherichia coli but controlled a different set of
      target genes, including sinE, which encodes an endoribonuclease. Expression, gel
      mobility shift, and mutational analyses indicated that sinE is a direct target of
      SoxR. Redox potentials and permeability of RACs determined optimal sinE
      induction. Bioinformatics suggested that only a few gamma- and beta
      proteobacteria might have SoxR-regulated sinE Purified SinE, in the presence of
      Mg2+ ions, degrades rRNAs, thus inhibiting protein synthesis. Similarly,
      pretreatment of cells with RACs demonstrated a role for SinE in promoting
      persistence in the presence of antibiotics that inhibit protein synthesis. Our
      data improve our understanding of the physiology of soil microorganisms by
      suggesting that both non-enteric SoxR and its target SinE play protective roles
      in the presence of RACs and antibiotics.

PMID- 27895127
TI  - The Pathogenic Potential of Proteus mirabilis Is Enhanced by Other Uropathogens
      during Polymicrobial Urinary Tract Infection.
AB  - Urinary catheter use is prevalent in health care settings, and polymicrobial
      colonization by urease-positive organisms, such as Proteus mirabilis and
      Providencia stuartii, commonly occurs with long-term catheterization. We
      previously demonstrated that coinfection with P. mirabilis and P. stuartii
      increased overall urease activity in vitro and disease severity in a model of
      urinary tract infection (UTI). In this study, we expanded these findings to a
      murine model of catheter-associated UTI (CAUTI), delineated the contribution of
      enhanced urease activity to coinfection pathogenesis, and screened for enhanced
      urease activity with other common CAUTI pathogens. In the UTI model, mice
      coinfected with the two species exhibited higher urine pH values, urolithiasis,
      bacteremia, and more pronounced tissue damage and inflammation compared to the
      findings for mice infected with a single species, despite having a similar
      bacterial burden within the urinary tract. The presence of P. stuartii,
      regardless of urease production by this organism, was sufficient to enhance P.
      mirabilis urease activity and increase disease severity, and enhanced urease
      activity was the predominant factor driving tissue damage and the dissemination
      of both organisms to the bloodstream during coinfection. These findings were
      largely recapitulated in the CAUTI model. Other uropathogens also enhanced P.
      mirabilis urease activity in vitro, including recent clinical isolates of
      Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas
      aeruginosa We therefore conclude that the underlying mechanism of enhanced urease
      activity may represent a widespread target for limiting the detrimental
      consequences of polymicrobial catheter colonization, particularly by P. mirabilis
      and other urease-positive bacteria.

PMID- 27895126
TI  - Versican Deficiency Significantly Reduces Lung Inflammatory Response Induced by
      Polyinosine-Polycytidylic Acid Stimulation.
AB  - Viral infection is an exacerbating factor contributing to chronic airway
      diseases, such as asthma, via mechanisms that are still unclear. Polyinosine
      polycytidylic acid (poly(I:C)), a Toll-like receptor 3 (TLR3) agonist used as a
      mimetic to study viral infection, has been shown to elicit inflammatory responses
      in lungs and to exacerbate pulmonary allergic reactions in animal models.
      Previously, we have shown that poly(I:C) stimulates lung fibroblasts to
      accumulate an extracellular matrix (ECM), enriched in hyaluronan (HA) and its
      binding partner versican, which promotes monocyte adhesion. In the current study,
      we aimed to determine the in vivo role of versican in mediating inflammatory
      responses in poly(I:C)-induced lung inflammation using a tamoxifen-inducible
      versican-deficient mouse model (Vcan-/- mice). In C57Bl/6 mice, poly(I:C)
      instillation significantly increased accumulation of versican and HA, especially
      in the perivascular and peribronchial regions, which were enriched in
      infiltrating leukocytes. In contrast, versican-deficient (Vcan-/-) lungs did not
      exhibit increases in versican or HA in these regions and had strikingly reduced
      numbers of leukocytes in the bronchoalveolar lavage fluid and lower expression of
      inflammatory chemokines and cytokines. Poly(I:C) stimulation of lung fibroblasts
      isolated from control mice generated HA-enriched cable structures in the ECM,
      providing a substrate for monocytic cells in vitro, whereas lung fibroblasts from
      Vcan-/- mice did not. Moreover, increases in proinflammatory cytokine expression
      were also greatly attenuated in the Vcan-/- lung fibroblasts. These findings
      provide strong evidence that versican is a critical inflammatory mediator during
      poly(I:C)-induced acute lung injury and, in association with HA, generates an ECM
      that promotes leukocyte infiltration and adhesion.

PMID- 27895128
TI  - Characterization of the Pathogenicity of Streptococcus intermedius TYG1620
      Isolated from a Human Brain Abscess Based on the Complete Genome Sequence with
      Transcriptome Analysis and Transposon Mutagenesis in a Murine Subcutaneous
      Abscess Model.
AB  - Streptococcus intermedius is known to cause periodontitis and pyogenic infections
      in the brain and liver. Here we report the complete genome sequence of strain
      TYG1620 (genome size, 2,006,877 bp; GC content, 37.6%; 2,020 predicted open
      reading frames [ORFs]) isolated from a brain abscess in an infant. Comparative
      analysis of S. intermedius genome sequences suggested that TYG1620 carries a
      notable type VII secretion system (T7SS), two long repeat regions, and 19 ORFs
      for cell wall-anchored proteins (CWAPs). To elucidate the genes responsible for
      the pathogenicity of TYG1620, transcriptome analysis was performed in a murine
      subcutaneous abscess model. The results suggest that the levels of expression of
      small hypothetical proteins similar to phenol-soluble modulin beta1 (PSMbeta1), a
      staphylococcal virulence factor, significantly increased in the abscess model. In
      addition, an experiment in a murine subcutaneous abscess model with random
      transposon (Tn) mutant attenuation suggested that Tn mutants with mutations in
      212 ORFs in the Tn mutant library were attenuated in the murine abscess model
      (629 ORFs were disrupted in total); the 212 ORFs are putatively essential for
      abscess formation. Transcriptome analysis identified 37 ORFs, including paralogs
      of the T7SS and a putative glucan-binding CWAP in long repeat regions, to be
      upregulated and attenuated in vivo This study provides a comprehensive
      characterization of S. intermedius pathogenicity based on the complete genome
      sequence and a murine subcutaneous abscess model with transcriptome and Tn
      mutagenesis, leading to the identification of pivotal targets for vaccines or
      antimicrobial agents for the control of S. intermedius infections.

PMID- 27895129
TI  - The Predicted Lytic Transglycosylase HpaH from Xanthomonas campestris pv.
      vesicatoria Associates with the Type III Secretion System and Promotes Effector
      Protein Translocation.
AB  - The pathogenicity of the Gram-negative plant-pathogenic bacterium Xanthomonas
      campestris pv. vesicatoria depends on a type III secretion (T3S) system, which
      spans both bacterial membranes and translocates effector proteins into plant
      cells. The assembly of the T3S system presumably involves the predicted lytic
      transglycosylase (LT) HpaH, which is encoded adjacent to the T3S gene cluster.
      Bacterial LTs degrade peptidoglycan and often promote the formation of membrane
      spanning macromolecular protein complexes. In the present study, we show that
      HpaH localizes to the bacterial periplasm and binds to peptidoglycan as well as
      to components of the T3S system, including the predicted periplasmic inner rod
      proteins HrpB1 and HrpB2 as well as the pilus protein HrpE. In vivo translocation
      assays revealed that HpaH promotes the translocation of various effector proteins
      and of early substrates of the T3S system, suggesting a general contribution of
      HpaH to type III-dependent protein export. Mutant studies and the analysis of
      reporter fusions showed that the N-terminal region of HpaH contributes to protein
      function and is proteolytically cleaved. The N-terminally truncated HpaH cleavage
      product is secreted into the extracellular milieu by a yet-unknown transport
      pathway, which is independent of the T3S system.

PMID- 27895130
TI  - MetQ of Neisseria gonorrhoeae Is a Surface-Expressed Antigen That Elicits
      Bactericidal and Functional Blocking Antibodies.
AB  - Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection
      (STI) gonorrhea, is a growing public health threat for which a vaccine is
      urgently needed. We characterized the functional role of the gonococcal MetQ
      protein, which is the methionine binding component of an ABC transporter system,
      and assessed its potential as a candidate antigen for inclusion in a gonococcal
      vaccine. MetQ has been found to be highly conserved in all strains investigated
      to date, it is localized on the bacterial surface, and it binds l-methionine with
      a high affinity. MetQ is also involved in gonococcal adherence to cervical
      epithelial cells. Mutants lacking MetQ have impaired survival in human monocytes,
      macrophages, and serum. Furthermore, antibodies raised against MetQ are
      bactericidal and are able to block gonococcal adherence to epithelial cells.
      These data suggest that MetQ elicits both bactericidal and functional blocking
      antibodies and is a valid candidate antigen for additional investigation and
      possible inclusion in a vaccine for prevention of gonorrhea.

PMID- 27895131
TI  - The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as
      a Candidate for Preerythrocytic and Transmission-Blocking Vaccines.
AB  - Recent studies have shown that immune responses against the cell-traversal
      protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite
      infection. While these studies provide important evidence toward the development
      of vaccines targeting this protein, it remains unknown whether these responses
      could engage the Plasmodium falciparum CelTOS in vivo Using a newly developed
      rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS),
      we evaluated the protective effect of in vivo immune responses elicited by
      vaccination and assessed the neutralizing capacity of monoclonal antibodies
      specific against PfCelTOS. Mice immunized with recombinant P. falciparum CelTOS
      in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or
      glucopyranosyl lipid adjuvant-liposome-QS21 (GLA-LSQ) adjuvant system
      significantly inhibited sporozoite hepatocyte infection. Notably, monoclonal
      antibodies against PfCelTOS strongly inhibited oocyst development of P.
      falciparum and Plasmodium berghei expressing PfCelTOS in Anopheles gambiae
      mosquitoes. Taken together, our results demonstrate that anti-CelTOS responses
      elicited by vaccination or passive immunization can inhibit sporozoite and
      ookinete infection and impair vector transmission.

PMID- 27895133
TI  - Vancomycin and the Risk of AKI: Now Clearer than Mississippi Mud.

PMID- 27895132
TI  - Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein
      Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density
      during Influenza A Virus Coinfection.
AB  - An increase in Streptococcus pneumoniae nasopharynx (NP) colonization density
      during a viral coinfection initiates pathogenesis. To mimic natural S. pneumoniae
      pathogenesis, we commensally colonized the NPs of adult C57BL/6 mice with S.
      pneumoniae serotype (ST) 6A or 8 and then coinfected them with mouse-adapted H1N1
      influenza A virus (PR/8/34). S. pneumoniae established effective commensal
      colonization, and influenza virus coinfection caused S. pneumoniae NP density to
      increase, resulting in bacteremia and mortality. We then studied histidine triad
      protein D (PhtD), an S. pneumoniae adhesin vaccine candidate, for its ability to
      prevent invasive S. pneumoniae disease in adult and infant mice. In adult mice,
      the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination
      with PCV13 led to a greater reduction of S. pneumoniae NP density (>2.5 log
      units) than PhtD vaccination (~1-log-unit reduction). However, no significant
      difference was observed with regard to the prevention of S. pneumoniae
      bacteremia, and there was no difference in mortality. Depletion of CD4+ T cells
      in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of
      vaccine-induced protection. In infant mice, passive transfer of antisera or CD4+
      T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP
      colonization density, whereas passive transfer of antisera and CD4+ T cells was
      needed to cause a significant reduction in NP colonization density. For the first
      time, these data show an outcome with regard to prevention of invasive S.
      pneumoniae pathogenesis with a protein vaccine similar to that which occurs with
      a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.

PMID- 27895134
TI  - Vancomycin and the Risk of AKI: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND OBJECTIVES: Vancomycin has been in use for more than half a
      century, but whether it is truly nephrotoxic and to what extent are still highly
      controversial. The objective of this study was to determine the risk of AKI
      attributable to intravenous vancomycin. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We conducted a systematic review of randomized, controlled trials
      and cohort studies that compared patients treated with intravenous vancomycin
      with a control group of patients given a comparator nonglycopeptide antibiotic
      and in which kidney function or kidney injury outcomes were reported. PubMed and
      Cochrane Library were searched from 1990 to September of 2015. Two reviewers
      extracted data and assessed study risk of bias, and one reviewer adjudicated the
      assessments. A meta-analysis was conducted on seven randomized, controlled trials
      (total of 4033 patients). RESULTS: Moderate quality evidence suggested that
      vancomycin treatment is associated with a higher risk of AKI, with a relative
      risk of 2.45 (95% confidence interval, 1.69 to 3.55). The risk of kidney injury
      was similar in patients treated for skin and soft tissue infections compared with
      those treated for nosocomial pneumonia and other complicated infections. There
      was an uncertain risk of reporting bias, because kidney function was not a
      prespecified outcome in any of the trials. The preponderance of evidence was
      judged to be indirect, because the majority of studies compared vancomycin
      specifically with linezolid. CONCLUSIONS: Our findings suggest that there is a
      measurable risk of AKI associated with vancomycin, but the strength of the
      evidence is moderate. A randomized, controlled trial designed to study kidney
      function as an outcome would be needed to draw unequivocal conclusions.

PMID- 27895135
TI  - Dialysis Vintage and Outcomes after Kidney Transplantation: A Retrospective
      Cohort Study.
AB  - BACKGROUND AND OBJECTIVES: Historically, length of pretransplant dialysis was
      associated with premature graft loss and mortality after kidney transplantation,
      but with recent advancements in RRT it is unclear whether this negative
      association still exists. DESIGN, SETTING, PARTICIPANTS, &MEASUREMENTS: This is a
      retrospective cohort study evaluating 6979 first kidney allograft recipients from
      the Austrian Registry transplanted between 1990 and 2013. Duration of
      pretransplant dialysis treatment was used as categoric predictor classified by
      tertiles of the distribution of time on dialysis. A separate category for pre
      emptive transplantation was added and defined as kidney transplantation without
      any dialysis preceding the transplant. Outcomes were death-censored graft loss,
      all-cause mortality, and the composite of both. RESULTS: Median duration of
      follow-up was 8.2 years, and 1866 graft losses and 2407 deaths occurred during
      the study period. Pre-emptive transplantation was associated with a lower risk of
      graft loss (hazard ratio, 0.76; 95% confidence interval, 0.59 to 0.98), but not
      in subgroup analyses excluding living transplants and transplants performed since
      2000. The association between dialysis duration and graft loss did not depend on
      the year of transplantation (P=0.40) or donor source (P=0.92). Longer waiting
      time on dialysis was not associated with a higher rate of graft loss, but the
      rate of death was higher in patients on pretransplant dialysis for >1.5 years
      (hazard ratio, 1.62; 95% confidence interval, 1.43 to 1.83) compared with
      pretransplant dialysis for <1.5 years. CONCLUSIONS: Our findings support the
      evidence that pre-emptive transplantation is associated with superior graft
      survival compared with pretransplant dialysis, although this association was
      weaker in transplants performed since 2000. However, our analysis shows that
      length of dialysis was no longer associated with a higher rate of graft loss,
      although longer waiting times on dialysis were still associated with a higher
      rate of death.

PMID- 27895137
TI  - Successful response to pegylated interferon alpha in a patient with recurrent
      paraganglioma.

PMID- 27895138
TI  - Urotensin II inhibitor eases neuropathic pain by suppressing the JNK/NF-kappaB
      pathway.
AB  - Urotensin II (U-II), a cyclic peptide originally isolated from the caudal
      neurosecretory system of fishes, can produce proinflammatory effects through its
      specific G protein-coupled receptor, GPR14. Neuropathic pain, a devastating
      disease, is related to excessive inflammation in the spinal dorsal horn. However,
      the relationship between U-II and neuropathic pain has not been reported. This
      study was designed to investigate the effect of U-II antagonist on neuropathic
      pain and to understand the associated mechanisms. We reported that U-II and its
      receptor GPR14 were persistently upregulated and activated in the dorsal horn of
      L4-6 spinal cord segments after chronic constriction injury (CCI) in rats.
      Intrathecal injection of SB657510, a specific antagonist against U-II, reversed
      CCI-induced thermal hyperalgesia and mechanical allodynia. Furthermore, we found
      that SB657510 reduced the expression of phosphorylated c-Jun N-terminal kinase (p
      JNK) and nuclear factor-kappaB (NF-kappaB) p65 as well as subsequent secretion of
      interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha).
      It was also showed that both the JNK inhibitor SP600125 and the NF-kappaB
      inhibitor PDTC significantly attenuated thermal hyperalgesia and mechanical
      allodynia in CCI rats. Our present research showed that U-II receptor antagonist
      alleviated neuropathic pain possibly through the suppression of the JNK/NF-kappaB
      pathway in CCI rats, which will contribute to the better understanding of
      function of U-II and pathogenesis of neuropathic pain.

PMID- 27895136
TI  - Recognition and Management of Resistant Hypertension.
AB  - Despite improvements in hypertension awareness and treatment, 30%-60% of
      hypertensive patients do not achieve BP targets and subsequently remain at risk
      for target organ damage. This therapeutic gap is particularly important to
      nephrologists, who frequently encounter treatment-resistant hypertension in
      patients with CKD. Data are limited on how best to treat patients with CKD and
      resistant hypertension, because patients with CKD have historically been excluded
      from hypertension treatment trials. First, we propose a consistent definition of
      resistant hypertension as BP levels confirmed by both in-office and out-of-office
      measurements that exceed appropriate targets while the patient is receiving
      treatment with at least three antihypertensive medications, including a diuretic,
      at dosages optimized to provide maximum benefit in the absence of intolerable
      side effects. Second, we recommend that each patient undergo a standardized,
      stepwise evaluation to assess adherence to dietary and lifestyle modifications
      and antihypertensive medications to identify and reduce barriers and discontinue
      use of substances that may exacerbate hypertension. Patients in whom there is
      high clinical suspicion should be evaluated for potential secondary causes of
      hypertension. Evidence-based management of resistant hypertension is discussed
      with special considerations of the differences in approach to patients with and
      without CKD, including the specific roles of diuretics and mineralocorticoid
      receptor antagonists and the current place of emerging therapies, such as renal
      denervation and baroreceptor stimulation. We endorse use of such a systematic
      approach to improve recognition and care for this vulnerable patient group that
      is at high risk for future kidney and cardiovascular events.

PMID- 27895140
TI  - Cathartic narratives for chaotic thinking.

PMID- 27895141
TI  - Extracorporeal membrane oxygenation for the treatment of severe refractory
      hantavirus cardiopulmonary syndrome.

PMID- 27895142
TI  - Curb prescriptions to combat opioid crisis.

PMID- 27895139
TI  - Human Spermatozoa Quantitative Proteomic Signature Classifies Normo- and
      Asthenozoospermia.
AB  - Scarcely understood defects lead to asthenozoospermia, which results in poor
      fertility outcomes. Incomplete knowledge of these defects hinders the development
      of new therapies and reliance on interventional therapies, such as in vitro
      fertilization, increases. Sperm cells, being transcriptionally and
      translationally silent, necessitate the proteomic approach to study the sperm
      function. We have performed a differential proteomics analysis of human sperm and
      seminal plasma and identified and quantified 667 proteins in sperm and 429
      proteins in seminal plasma data set, which were used for further analysis.
      Statistical and mathematical analysis combined with pathway analysis and self
      organizing maps clustering and correlation was performed on the data set.It was
      found that sperm proteomic signature combined with statistical analysis as
      opposed to the seminal plasma proteomic signature can differentiate the
      normozoospermic versus the asthenozoospermic sperm samples. This is despite the
      results that some of the seminal plasma proteins have big fold changes among
      classes but they fall short of statistical significance. S-Plot of the sperm
      proteomic data set generated some high confidence targets, which might be
      implicated in sperm motility pathways. These proteins also had the area under the
      curve value of 0.9 or 1 in ROC curve analysis.Various pathways were either
      enriched in these proteomic data sets by pathway analysis or they were searched
      by their constituent proteins. Some of these pathways were axoneme activation and
      focal adhesion assembly, glycolysis, gluconeogenesis, cellular response to stress
      and nucleosome assembly among others. The mass spectrometric data is available
      via ProteomeXchange with identifier PXD004098.

PMID- 27895144
TI  - Should Canada focus on antimicrobial resistance?

PMID- 27895143
TI  - Physicians combat opioid crisis.

PMID- 27895145
TI  - Association between inflammatory biomarkers and all-cause, cardiovascular and
      cancer-related mortality.
AB  - BACKGROUND: The inflammatory biomarker alpha1-acid glycoprotein (AGP) was found
      to have the strongest association with 5-year mortality in a recent study of 106
      biomarkers. We examined whether AGP is a better biomarker of mortality risk than
      the more widely used inflammatory biomarkers interleukin-6 (IL-6) and C-reactive
      protein (CRP). METHODS: We analyzed data for 6545 men and women aged 45-69 (mean
      55.7) years from the Whitehall II cohort study. We assayed AGP, IL-6 and CRP
      levels from fasting serum samples collected in 1997-1999. Mortality followup was
      until June 2015. Cox regression analysis was used to model associations of
      inflammatory biomarkers with all-cause, cardiovascular and cancer-related
      mortality. RESULTS: Over the mean follow-up of 16.7 years, 736 deaths occurred,
      of which 181 were from cardiovascular disease and 347 from cancer. In the model
      adjusted for all covariates (age, sex, socioeconomic status, body mass index,
      health behaviours and chronic disease), AGP did not predict mortality beyond the
      first 5 years of follow-up; over this period, IL-6 and CRP had stronger
      associations with mortality. When we considered all covariates and biomarkers
      simultaneously, AGP no longer predicted all-cause mortality over the entire
      follow-up period (adjusted hazard ratio [HR] 0.99, 95% confidence interval [CI]
      0.90-1.08). Only IL-6 predicted all-cause mortality (adjusted HR 1.22, 95% CI
      1.12-1.33) and cancer-related mortality (adjusted HR 1.13, 95% CI 1.00-1.29) over
      the entire follow-up period, whereas CRP predicted only cardiovascular mortality
      (adjusted HR 1.30, 95% CI 1.06-1.61). INTERPRETATION: Our findings suggest that
      AGP is not a better marker of short-or long-term mortality risk than the more
      commonly used biomarkers IL-6 and CRP.

PMID- 27895146
TI  - Improving diagnosis of pediatric central nervous system tumours: aiming for early
      detection.

PMID- 27895147
TI  - Inflammation, cardiovascular disease and cancer: moving toward predictive
      medicine.

PMID- 27895148
TI  - TrpC5 regulates differentiation through the Ca2+/Wnt5a signalling pathway in
      colorectal cancer.
AB  - Transient receptor potential channel 5 (TrpC5) is a member of the TrpC subgroup,
      and it forms a receptor-activated, non-selective Ca2+ channel. The architecture
      of the TrpC5 channel is poorly understood. In the present study, we report that
      TrpC5 is a key factor in regulating differentiation in colorectal cancer (CRC).
      Through a study of specimens from a large cohort of patients with CRC, we found
      that TrpC5 was highly expressed and its cellular level correlated with tumour
      grade. We showed further that up-regulated TrpC5 caused a robust rise in
      intracellular calcium concentration [Ca2+]i, increased Wnt5a expression and the
      nuclear translocation of beta-catenin, leading to a reduction in cancer
      differentiation and an increase in cancer cell stemness. Notably, patients with
      tumours that expressed high levels of TrpC5 showed significantly poorer disease
      free and overall survival. Therefore, our findings suggest that TrpC5 is an
      independent adverse prognostic factor for death in CRC, reducing differentiation
      through the Ca2+/Wnt5a signalling pathway.

PMID- 27895149
TI  - Psychotherapy for Adolescents With Attention-Deficit Hyperactivity Disorder: A
      Pediatrician's Guide.
AB  - Attention-deficit hyperactivity disorder (ADHD) presents with high levels of
      inattention, impulsiveness, and hyperactivity. ADHD starts in childhood and
      results in impairments that continue into adulthood. ADHD symptoms lead to
      decreased functionality in various life domains and result in poor academics,
      behavioral challenges, delayed independence, and strained relationships. Despite
      advances in diagnosis and treatment, persistent residual symptoms are common,
      highlighting the need for novel treatment strategies. This article aims to
      provide a review of the psychotherapeutic interventions available for teens that
      receive pharmacotherapy but continue to struggle with the residual symptoms of
      ADHD that interfere with academic function, relationship formation, and
      psychological development.

PMID- 27895150
TI  - Effects of VA Facility Dog on Hospitalized Veterans Seen by a Palliative Care
      Psychologist: An Innovative Approach to Impacting Stress Indicators.
AB  - The United States is home to 23 million veterans. In many instances, veterans
      with serious illness who seek healthcare at the VA receive care from a palliative
      care service. Animal-assisted intervention (AAI) is gaining attention as a
      therapeutic stress reducing modality; however, its effects have not been well
      studied in veterans receiving palliative care in an acute care setting. A
      crossover repeated-measures study was conducted to examine the effects of an
      animal-assisted intervention (AAI) in the form of a therapy dog on stress
      indicators in 25 veterans on the palliative care service at the VA Eastern
      Colorado Healthcare System in Denver, CO. Veterans had a visit from a therapy dog
      and the dog's handler, a clinical psychologist (experimental condition) and an
      unstructured visit with the clinical psychologist alone (control condition).
      Blood pressure, heart rate, and the salivary biomarkers cortisol, alpha-amylase,
      and immunoglobulin A were collected before, after, and 30-minutes after both the
      experimental and control conditions. Significant decreases in cortisol were found
      when the before time period was compared to the 30-minutes after time period for
      both the experimental ( p = 0.007) and control condition ( p = 0.036). A
      significant decrease in HR was also found when the before time period was
      compared to the 30-minutes after time period for both the experimental ( p =
      0.0046) and control ( p = 0.0119) condition. Results of this study supported that
      a VA facility dog paired with a palliative care psychologist had a measurable
      impact on salivary cortisol levels and HR in veterans.

PMID- 27895151
TI  - A High-Fat Diet Promotes Mammary Gland Myofibroblast Differentiation through
      MicroRNA 140 Downregulation.
AB  - Human breast adipose tissue is a heterogeneous cell population consisting of
      mature white adipocytes, multipotent mesenchymal stem cells, committed progenitor
      cells, fibroblasts, endothelial cells, and immune cells. Dependent on external
      stimulation, adipose-derived stem cells differentiate along diverse lineages into
      adipocytes, chondrocytes, osteoblasts, fibroblasts, and myofibroblasts. It is
      currently not fully understood how a high-fat diet reprograms adipose-derived
      stem cells into myofibroblasts. In our study, we used mouse models of a regular
      diet and of high-fat-diet-induced obesity to investigate the role of dietary fat
      on myofibroblast differentiation in the mammary stromal microenvironment. We
      found that a high-fat diet promotes myofibroblast differentiation by decreasing
      microRNA 140 (miR-140) expression in mammary adipose tissue through a novel
      negative-feedback loop. Increased transforming growth factor beta1 (TGF-beta1) in
      mammary adipose tissue in obese mice activates SMAD3 signaling, causing phospho
      SMAD3 to bind to the miR-140 locus and inhibit miR-140 transcription. This
      prevents miR-140 from targeting SMAD3 for degradation, resulting in amplified TGF
      beta1/SMAD3 signaling and miR-140 downregulation-dependent myofibroblast
      differentiation. Using tissue and coculture models, we found that myofibroblasts
      and the fibrotic microenvironment created by myofibroblasts impact the stemness
      and proliferation of normal ductal epithelial cells and early-stage breast cancer
      invasion and stemness.

PMID- 27895152
TI  - Spatiotemporal Uncoupling of MicroRNA-Mediated Translational Repression and
      Target RNA Degradation Controls MicroRNP Recycling in Mammalian Cells.
AB  - MicroRNA (miRNA)-mediated repression controls expression of more than half of
      protein-coding genes in metazoan animals. Translation repression is associated
      with target mRNA degradation initiated by decapping and deadenylation of the
      repressed mRNAs. Earlier evidence suggests the endoplasmic reticulum (ER) as the
      site where microRNPs (miRNPs) interact with their targets before translation
      repression sets in, but the subcellular location of subsequent degradation of
      miRNA-repressed messages is largely unidentified. Here, we explore the
      subcellular distribution of essential components of degradation machineries of
      miRNA-targeted mRNAs. We have noted that interaction of target mRNAs with AGO2
      protein on the ER precedes the relocalization of repressed messages to
      multivesicular bodies (MVBs). The repressed messages subsequently get
      deadenylated, lose their interaction with AGO2, and become decapped. Blocking
      maturation of endosomes to late endosome and MVBs by targeting the endosomal
      protein HRS uncouples miRNA-mediated translation repression from target RNA
      degradation. HRS is also targeted by the intracellular parasite Leishmania
      donovani, which curtails the HRS level in infected cells to prevent uncoupling of
      mRNA-AGO2 interaction, preventing degradation of translationally repressed
      messages, and thus stops recycling of miRNPs preengaged in repression.

PMID- 27895153
TI  - Ubiquitylation of Ku80 by RNF126 Promotes Completion of Nonhomologous End Joining
      Mediated DNA Repair.
AB  - Repair of damaged DNA is critical for maintenance of genetic information. In
      eukaryotes, DNA double-strand breaks (DSBs) are recognized by the Ku70-Ku80
      heterodimer, which then recruits proteins that mediate repair by nonhomologous
      end joining (NHEJ). Prolonged retention of Ku70/80 at DSBs prevents completion of
      repair, however, with ubiquitylation of Ku80 having been implicated in Ku70/80
      dissociation from DNA. Here, we identify RNF126 as a ubiquitin ligase that is
      recruited to DSBs and ubiquitylates Ku80, with UBE2D3 serving as an E2 enzyme.
      Knockdown of RNF126 prevented Ku70/80 dissociation from DSBs and inhibited break
      repair. Attenuation of Ku80 ubiquitylation by replacement of ubiquitylation site
      lysines with arginine residues delayed Ku70/80 release from chromatin after DSB
      induction by genotoxic insults. Together, our data indicate that RNF126 is a
      novel regulator of NHEJ that promotes completion of DNA repair by ubiquitylating
      Ku80 and releasing Ku70/80 from damaged DNA.

PMID- 27895154
TI  - Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy.
AB  - Lowe syndrome and Dent disease are two conditions that result from mutations of
      the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share
      the feature of impaired kidney proximal tubule function. Genetic ablation of Ocrl
      in mice failed to recapitulate the human phenotypes, possibly because of the
      redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5
      phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early
      embryonic lethality. We report that kidney tubule-specific inactivation of Inpp5b
      on a global Ocrl-knockout mouse background resulted in low molecular weight
      proteinuria, phosphaturia, and acidemia. At the cellular level, we observed a
      striking impairment of clathrin-dependent and -independent endocytosis in
      proximal tubules, phenocopying what has been reported for Dent disease caused by
      mutations in the gene encoding endosomal proton-chloride exchange transporter 5.
      These results suggest that the functions of OCRL/INPP5B and proton-chloride
      exchange transporter 5 converge on shared mechanisms, the impairment of which has
      a dramatic effect on proximal tubule endocytosis.

PMID- 27895155
TI  - Investigations of Glucocorticoid Action in GN.
AB  - For several decades, glucocorticoids have been used empirically to treat rapid
      progressive GN. It is commonly assumed that glucocorticoids act primarily by
      dampening the immune response, but the mechanisms remain incompletely understood.
      In this study, we inactivated the glucocorticoid receptor (GR) specifically in
      kidney epithelial cells using Pax8-Cre/GRfl/fl mice. Pax8-Cre/GRfl/fl mice did
      not exhibit an overt spontaneous phenotype. In mice treated with nephrotoxic
      serum to induce crescentic nephritis (rapidly progressive GN), this genetic
      inactivation of the GR in kidney epithelial cells exerted renal benefits,
      including inhibition of albuminuria and cellular crescent formation, similar to
      the renal benefits observed with high-dose prednisolone in control mice. However,
      genetic inactivation of the GR in kidney epithelial cells did not induce the
      immunosuppressive effects observed with prednisolone. In vitro, prednisolone and
      the pharmacologic GR antagonist mifepristone each acted directly on primary
      cultures of parietal epithelial cells, inhibiting cellular outgrowth and
      proliferation. In wild-type mice, pharmacologic treatment with the GR antagonist
      mifepristone also attenuated disease as effectively as high-dose prednisolone
      without the systemic immunosuppressive effects. Collectively, these data show
      that glucocorticoids act directly on activated glomerular parietal epithelial
      cells in crescentic nephritis. Furthermore, we identified a novel therapeutic
      approach in crescentic nephritis, that of glucocorticoid antagonism, which was at
      least as effective as high-dose prednisolone with potentially fewer adverse
      effects.

PMID- 27895156
TI  - Sildenafil Prevents Podocyte Injury via PPAR-gamma-Mediated TRPC6 Inhibition.
AB  - Transient receptor potential channel C6 (TRPC6) gain-of-function mutations and
      increased TRPC6 expression in podocytes induce glomerular injury and proteinuria.
      Sildenafil reduces TRPC6 expression and activity in nonrenal cell types, although
      the mechanism is unknown. Peroxisome proliferator-activated receptor gamma (PPAR
      gamma) is a downstream target of sildenafil in the cyclic guanosine monophosphate
      (cGMP)-activated protein kinase G (PKG) axis. PPAR-gamma agonists, like
      pioglitazone, appear antiproteinuric. We hypothesized that sildenafil inhibits
      TRPC6 expression in podocytes through PPAR-gamma-dependent mechanisms, thereby
      counteracting podocyte injury and proteinuria. Treatment with sildenafil, the
      cGMP derivative 8-bromoguanosine 3',5'-cyclic monophosphate sodium salt (8-Br
      cGMP), or pioglitazone dose-dependently downregulated podocyte injury-induced
      TRPC6 expression in vitro Knockdown or application of antagonists of PKG or PPAR
      gamma enhanced TRPC6 expression in podocytes and counteracted effects of
      sildenafil and 8-Br-cGMP. We observed similar effects on TRPC6 promoter activity
      and TRPC6-dependent calcium influx. Chromatin immunoprecipitation showed PPAR
      gamma binding to the TRPC6 promoter. Sildenafil or pioglitazone treatment
      prevented proteinuria and the increased TRPC6 expression in rats with adriamycin
      induced nephropathy and mice with hyperglycemia-induced renal injury. Rats
      receiving PPAR-gamma antagonists displayed proteinuria and increased podocyte
      TRPC6 expression, as did podocyte-specific PPAR-gamma knockout mice, which were
      more sensitive to adriamycin and not protected by sildenafil. Thus, sildenafil
      ameliorates podocyte injury and prevents proteinuria through cGMP- and PKG
      dependent binding of PPAR-gamma to the TRPC6 promoter, which inhibits TRPC6
      promoter activity, expression, and activity. Because sildenafil is approved for
      clinical use, our results suggest that additional clinical study of its
      antiproteinuric effect in glomerular disease is warranted.

PMID- 27895157
TI  - Beneficial Effects of Myo-Inositol Oxygenase Deficiency in Cisplatin-Induced AKI.
AB  - Overexpression of the proximal tubular enzyme myo-inositol oxygenase (MIOX)
      induces oxidant stress in vitro However, the relevance of MIOX to tubular
      pathobiology remains enigmatic. To investigate the role of MIOX in cisplatin
      induced tubular AKI, we generated conditional MIOX-overexpressing transgenic
      (MIOX-TG) mice and MIOX-knockout (MIOX-/-) mice with tubule-specific MIOX
      overexpression or knockout, respectively. Compared with cisplatin-treated wild
      type (WT) mice, cisplatin-treated MIOX-TG mice had even greater increases in
      urea, creatinine, and KIM-1 levels and more tubular injury and apoptosis, but
      these effects were attenuated in cisplatin-treated MIOX-/- mice. Similarly, MIOX
      TG mice had the highest and MIOX-/- mice had the lowest renal levels of Bax,
      cleaved caspase-3, and NADPH oxidase-4 expression and reactive oxygen species
      (ROS) generation after cisplatin treatment. In vitro, cisplatin dose-dependently
      increased ROS generation in LLC-PK1 cells. Furthermore, MIOX overexpression in
      these cells accentuated cisplatin-induced ROS generation and perturbations in the
      ratio of GSH to oxidized GSH, whereas MIOX-siRNA or N-acetyl cysteine treatment
      attenuated these effects. Additionally, the cisplatin-induced enhancement of p53
      activation, NF-kappaB binding to DNA, and NF-kappaB nuclear translocation in WT
      mice was exacerbated in MIOX-TG mice but absent in MIOX-/- mice. In vitro, MIOX
      siRNA or NAC treatment reduced the dose-dependent increase in p53 expression
      induced by cisplatin. We also observed a remarkable influx of inflammatory cells
      and upregulation of cytokines in kidneys of cisplatin-treated MIOX-TG mice.
      Finally, analysis of genomic DNA in WT mice revealed cisplatin-induced
      hypomethylation of the MIOX promoter. These data suggest that MIOX overexpression
      exacerbates, whereas MIOX gene disruption protects against, cisplatin-induced
      AKI.

PMID- 27895161
TI  - The E Loop of the Transmitter Binding Site Is a Key Determinant of the Modulatory
      Effects of Physostigmine on Neuronal Nicotinic alpha4beta2 Receptors.
AB  - Physostigmine is a well known inhibitor of acetylcholinesterase, which can also
      activate, potentiate, and inhibit acetylcholine receptors, including neuronal
      nicotinic receptors comprising alpha4 and beta2 subunits. We have found that the
      two stoichiometric forms of this receptor differ in the effects of physostigmine.
      The form containing three copies of alpha4 and two of beta2 was potentiated at
      low concentrations of acetylcholine chloride (ACh) and physostigmine, whereas the
      form containing two copies of alpha4 and three of beta2 was inhibited. Chimeric
      constructs of subunits indicated that the presence of inhibition or potentiation
      depended on the source of the extracellular ligand binding domain of the subunit.
      Further sets of chimeric constructs demonstrated that a portion of the ACh
      binding domain, the E loop, is a key determinant. Transferring the E loop from
      the beta2 subunit to the alpha4 subunit resulted in strong inhibition, whereas
      the reciprocal transfer reduced inhibition. To control the number and position of
      the incorporated chimeric subunits, we expressed chimeric constructs with subunit
      dimers. Surprisingly, incorporation of a subunit with an altered E loop had
      similar effects whether it contributed either to an intersubunit interface
      containing a canonical ACh binding site or to an alternative interface. The
      observation that the alpha4 E loop is involved suggests that physostigmine
      interacts with regions of subunits that contribute to the ACh binding site,
      whereas the lack of interface specificity indicates that interaction with a
      particular ACh binding site is not the critical factor.

PMID- 27895163
TI  - G-Protein-Coupled Receptor Kinase 2 as a Potential Modulator of the Hallmarks of
      Cancer.
AB  - Malignant features-such as sustained proliferation, refractoriness to growth
      suppressors, resistance to cell death or aberrant motility, and metastasis-can be
      triggered by a variety of mutations and signaling adaptations. Signaling nodes
      can act as cancer-associated factors by cooperating with oncogene-governed
      pathways or participating in compensatory transduction networks to strengthen
      tumor properties. G-protein-coupled receptor kinase 2 (GRK2) is arising as one of
      such nodes. Via its complex network of connections with other cellular proteins,
      GRK2 contributes to the modulation of basic cellular functions-such as cell
      proliferation, survival, or motility-and is involved in metabolic homeostasis,
      inflammation, or angiogenic processes. Moreover, altered GRK2 levels are starting
      to be reported in different tumoral contexts and shown to promote breast
      tumorigenesis or to trigger the tumoral angiogenic switch. The ability to
      modulate several of the hallmarks of cancer puts forward GRK2 as an oncomodifier,
      able to modulate carcinogenesis in a cell-type specific way.

PMID- 27895162
TI  - Cannabinoid Receptor Interacting Protein 1a Competition with beta-Arrestin for
      CB1 Receptor Binding Sites.
AB  - Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R)
      distal C-terminal-associated protein that alters CB1R interactions with G
      proteins. We tested the hypothesis that CRIP1a is capable of also altering CB1R
      interactions with beta-arrestin proteins that interact with the CB1R at the C
      terminus. Coimmunoprecipitation studies indicated that CB1R associates in
      complexes with either CRIP1a or beta-arrestin, but CRIP1a and beta-arrestin fail
      to coimmunoprecipitate with each other. This suggests a competition for CRIP1a
      and beta-arrestin binding to the CB1R, which we hypothesized could attenuate the
      action of beta-arrestin to mediate CB1R internalization. We determined that
      agonist-mediated reduction of the density of cell surface endogenously expressed
      CB1Rs was clathrin and dynamin dependent and could be modeled as agonist-induced
      aggregation of transiently expressed GFP-CB1R. CRIP1a overexpression attenuated
      CP55940-mediated GFP-CB1R as well as endogenous beta-arrestin redistribution to
      punctae, and conversely, CRIP1a knockdown augmented beta-arrestin redistribution
      to punctae. Peptides mimicking the CB1R C-terminus could bind to both CRIP1a in
      cell extracts as well as purified recombinant CRIP1a. Affinity pull-down studies
      revealed that phosphorylation at threonine-468 of a CB1R distal C-terminus 14-mer
      peptide reduced CB1R-CRIP1a association. Coimmunoprecipitation of CB1R protein
      complexes demonstrated that central or distal C-terminal peptides competed for
      the CB1R association with CRIP1a, but that a phosphorylated central C-terminal
      peptide competed for association with beta-arrestin 1, and phosphorylated central
      or distal C-terminal peptides competed for association with beta-arrestin 2.
      Thus, CRIP1a can compete with beta-arrestins for interaction with C-terminal CB1R
      domains that could affect agonist-driven, beta-arrestin-mediated internalization
      of the CB1R.

PMID- 27895164
TI  - MYSM1-dependent checkpoints in B cell lineage differentiation and B cell-mediated
      immune response.
AB  - MYSM1 is a chromatin-binding histone deubiquitinase. MYSM1 mutations in humans
      result in lymphopenia whereas loss of Mysm1 in mice causes severe hematopoietic
      abnormalities, including an early arrest in B cell development. However, it
      remains unknown whether MYSM1 is required at later checkpoints in B cell
      development or for B cell-mediated immune responses. We analyzed conditional
      mouse models Mysm1fl/flTg.mb1-cre, Mysm1fl/flTg.CD19-cre, and Mysm1fl/flTg.CD21
      cre with inactivation of Mysm1 at prepro-B, pre-B, and follicular B cell stages
      of development. We show that loss of Mysm1 at the prepro-B cell stage in
      Mysm1fl/flTg.mb1-cre mice results in impaired B cell differentiation, with an ~2
      fold reduction in B cell numbers in the lymphoid organs. Mysm1fl/flTg.mb1-cre B
      cells also showed increased expression of activation markers and impaired
      survival and proliferation. In contrast, Mysm1 was largely dispensable from the
      pre-B cell stage onward, with Mysm1fl/flTg.CD19-cre and Mysm1fl/flTg.CD21-cre
      mice showing no alterations in B cell numbers and largely normal responses to
      stimulation. MYSM1, therefore, has an essential role in B cell lineage
      specification but is dispensable at later stages of development. Importantly,
      MYSM1 activity at the prepro-B cell stage of development is important for the
      normal programming of B cell responses to stimulation once they complete their
      maturation process.

PMID- 27895165
TI  - Rats with a missense mutation in Atm display neuroinflammation and
      neurodegeneration subsequent to accumulation of cytosolic DNA following
      unrepaired DNA damage.
AB  - Mutations in the ataxia-telangiectasia (A-T)-mutated (ATM) gene give rise to the
      human genetic disorder A-T, characterized by immunodeficiency, cancer
      predisposition, and neurodegeneration. Whereas a series of animal models
      recapitulate much of the A-T phenotype, they fail to present with ataxia or
      neurodegeneration. We describe here the generation of an Atm missense mutant
      [amino acid change of leucine (L) to proline (P) at position 2262 (L2262P)] rat
      by intracytoplasmic injection (ICSI) of mutant sperm into oocytes. Atm-mutant
      rats (AtmL2262P/L2262P ) expressed low levels of ATM protein, suggesting a
      destabilizing effect of the mutation, and had a significantly reduced lifespan
      compared with Atm+/+ Whereas these rats did not show cerebellar atrophy, they
      succumbed to hind-limb paralysis (45%), and the remainder developed tumors.
      Closer examination revealed the presence of both dsDNA and ssDNA in the cytoplasm
      of cells in the hippocampus, cerebellum, and spinal cord of AtmL2262P/L2262P
      rats. Significantly increased levels of IFN-beta and IL-1beta in all 3 tissues
      were indicative of DNA damage induction of the type 1 IFN response. This was
      further supported by NF-kappaB activation, as evidenced by p65 phosphorylation
      (P65) and translocation to the nucleus in the spinal cord and parahippocampus.
      Other evidence of neuroinflammation in the brain and spinal cord was the loss of
      motor neurons and the presence of increased activation of microglia. These data
      provide support for a proinflammatory phenotype that is manifested in the Atm
      mutant rat as hind-limb paralysis. This mutant represents a useful model to
      investigate the importance of neuroinflammation in A-T.

PMID- 27895166
TI  - T cell-rich lymphoid infiltrates with large B cells: a review of key entities and
      diagnostic approach.
AB  - Accurate diagnostic interpretation of a lymphoid population composed
      predominantly of small T cells, together with smaller numbers of large B cells,
      with or without a nodular architecture, is a common problem faced by the
      histopathologist. The differential diagnosis of this histological pattern is
      wide, ranging from reactive conditions such as drug reactions and viral
      infections, through borderline entities such as immunodeficiency-related
      lymphoproliferative disorders to lymphomas. The latter includes entities where
      the large B cells are primarily neoplastic (classical and nodular lymphocyte
      predominant Hodgkin lymphomas and T cell/histiocyte-rich large B cell lymphoma)
      as well as T cell lymphomas such as angioimmunoblastic T cell lymphoma where the
      large B cells represent an epiphenomenon and may or may not be neoplastic.
      Several rare variants of these conditions, and the fact that treatment can
      significantly modify appearances, add to the diagnostic difficulty of these
      pathological entities. Unlike monomorphic lymphoid infiltrates, the histological
      pattern of T cell-rich proliferation with large B cells requires close evaluation
      of the inter-relationship between B cells and T cells, follicular dendritic cells
      and sometimes other inflammatory cells. Epstein-Barr virus plays a key role in
      several of these scenarios, and interpreting not only its presence but also its
      distribution within cellular subgroups is essential to accurate diagnosis and the
      avoidance of some important diagnostic pitfalls. An understanding of normal
      immunoarchitecture and lymphoid maturational pathways is also fundamental to
      resolving these cases, as is a knowledge of their common patterns of spread,
      which facilitates correlation with clinical and radiological findings.

PMID- 27895167
TI  - PGI2 Controls Pulmonary NK Cells That Prevent Airway Sensitization to House Dust
      Mite Allergen.
AB  - In allergic asthma, inhalation of airborne allergens such as the house dust mite
      (HDM) effectively activates both innate and adaptive immunity in the lung mucosa.
      To determine the role of the eicosanoid PGI2 and its receptor IP during allergic
      airway sensitization, HDM responses in mice lacking a functional IP receptor
      (i.e., PGI2 IP receptor-deficient [IP-/-]) were compared with wild type (WT)
      mice. Surprisingly, IP-/- mice had increased numbers of pulmonary CD3
      NK1.1+Ly49b+ NK cells producing IFN-gamma that was inversely associated with the
      number of type 2 innate lymphoid cells (ILC2s) expressing IL-33Ralpha and IL-13
      compared with WT animals. This phenomenon was associated with elevated CX3CL1
      levels in the airways of IP-/- mice and treatment with a neutralizing Ab to
      CX3CL1 reduced IFN-gamma production by the lung NK cells. Remarkably, IP-/- mice
      were less responsive to HDM challenge than WT counterparts because intranasal
      instillation of the allergen induced markedly reduced levels of airway
      eosinophils, CD4+ lymphocyte infiltration, and mucus production, as well as
      depressed levels of CCL2 chemokine and Th2 cytokines. NK cells were responsible
      for such attenuated responses because depletion of NK1.1+ cells in IP-/- mice
      restored both the HDM-induced lung inflammation and ILC2 numbers, whereas
      transfer of CD3-NK1.1+ NK cells into the airways of WT hosts suppressed the
      inflammatory response. Collectively, these data demonstrate a hitherto unknown
      role for PGI2 in regulating the number and properties of NK cells resident in
      lung tissue and reveal a role for NK cells in limiting lung tissue ILC2s and
      preventing allergic inflammatory responses to inhaled HDM allergen.

PMID- 27895168
TI  - CX3CR1+ Cell-Mediated Salmonella Exclusion Protects the Intestinal Mucosa during
      the Initial Stage of Infection.
AB  - During Salmonella Typhimurium infection, intestinal CX3CR1+ cells can either
      extend transepithelial cellular processes to sample luminal bacteria or, very
      early after infection, migrate into the intestinal lumen to capture bacteria.
      However, until now, the biological relevance of the intraluminal migration of
      CX3CR1+ cells remained to be determined. We addressed this by using a combination
      of mouse strains differing in their ability to carry out CX3CR1-mediated sampling
      and intraluminal migration. We observed that the number of S. Typhimurium
      traversing the epithelium did not differ between sampling-competent/migration
      competent C57BL/6 and sampling-deficient/migration-competent BALB/c mice. In
      contrast, in sampling-deficient/migration-deficient CX3CR1-/- mice the numbers of
      S. Typhimurium penetrating the epithelium were significantly higher. However, in
      these mice the number of invading S. Typhimurium was significantly reduced after
      the adoptive transfer of CX3CR1+ cells directly into the intestinal lumen,
      consistent with intraluminal CX3CR1+ cells preventing S. Typhimurium from
      infecting the host. This interpretation was also supported by a higher bacterial
      fecal load in CX3CR1+/gfp compared with CX3CR1gfp/gfp mice following oral
      infection. Furthermore, by using real-time in vivo imaging we observed that
      CX3CR1+ cells migrated into the lumen moving through paracellular channels within
      the epithelium. Also, we reported that the absence of CX3CR1-mediated sampling
      did not affect Ab responses to a noninvasive S. Typhimurium strain that
      specifically targeted the CX3CR1-mediated entry route. These data showed that the
      rapidly deployed CX3CR1+ cell-based mechanism of immune exclusion is a defense
      mechanism against pathogens that complements the mucous and secretory IgA Ab
      mediated system in the protection of intestinal mucosal surface.

PMID- 27895170
TI  - Prevention of Vgamma9Vdelta2 T Cell Activation by a Vgamma9Vdelta2 TCR Nanobody.
AB  - Vgamma9Vdelta2 T cell activation plays an important role in antitumor and
      antimicrobial immune responses. However, there are conditions in which
      Vgamma9Vdelta2 T cell activation can be considered inappropriate for the host.
      Patients treated with aminobisphosphonates for hypercalcemia or metastatic bone
      disease often present with a debilitating acute phase response as a result of
      Vgamma9Vdelta2 T cell activation. To date, no agents are available that can
      clinically inhibit Vgamma9Vdelta2 T cell activation. In this study, we describe
      the identification of a single domain Ab fragment directed to the TCR of
      Vgamma9Vdelta2 T cells with neutralizing properties. This variable domain of an H
      chain-only Ab (VHH or nanobody) significantly inhibited both phosphoantigen
      dependent and -independent activation of Vgamma9Vdelta2 T cells and, importantly,
      strongly reduced the production of inflammatory cytokines upon stimulation with
      aminobisphosphonate-treated cells. Additionally, in silico modeling suggests that
      the neutralizing VHH binds the same residues on the Vgamma9Vdelta2 TCR as the
      Vgamma9Vdelta2 T cell Ag-presenting transmembrane protein butyrophilin 3A1,
      providing information on critical residues involved in this interaction. The
      neutralizing Vgamma9Vdelta2 TCR VHH identified in this study might provide a
      novel approach to inhibit the unintentional Vgamma9Vdelta2 T cell activation as a
      consequence of aminobisphosphonate administration.

PMID- 27895169
TI  - Critical Role of LTB4/BLT1 in IL-23-Induced Synovial Inflammation and
      Osteoclastogenesis via NF-kappaB.
AB  - IL-23 activates the synthesis and production of leukotriene B4 (LTB4) in myeloid
      cells, which modulate inflammatory arthritis. In this study we investigated the
      role of LTB4 and its receptor LTB4R1 (BLT1) in synovial inflammation and
      osteoclast differentiation. Specifically, we used IL-23 in vivo gene transfer to
      induce arthritis in mice and showed that elevated serum LTB4 and synovial
      expression of 5-lipoxygenase correlated with increased disease severity by
      histological evaluation and paw swelling compared with GFP gene transfer
      controls. To further investigate the effect of the LTB4 pathway in bone loss, we
      performed osteoclast differentiation assays by stimulating with M-CSF and
      receptor activator of NF-kappaB ligand bone marrow cells derived from BLT1+/+
      and/or BLT1-/- mice and used quantitative PCR for gene expression analysis in
      terminally differentiated osteoclasts. Deficiency in BLT1 resulted in the
      upregulation of osteoclast-related genes and an increase in the formation of
      giant, multinucleated TRAP+ cells capable of F-actin ring formation.
      Additionally, BLT1 deficiency showed an increase of phosphorylated NF-kappaB and
      phosphorylated IkappaB levels in osteoclasts. We also performed real-time calcium
      imaging to study the effect of BLT1 deficiency in receptor activator of NF-kappa
      B ligand-induced activation of intracellular calcium flux in vitro. Our data show
      that LTB4 and its receptor BLT1 exacerbate synovial inflammation in vivo and bone
      resorption in vitro, suggesting that LTB4 and BLT1 could be effectively targeted
      for the treatment of musculoskeletal diseases.

PMID- 27895171
TI  - Impairment of CCR6+ and CXCR3+ Th Cell Migration in HIV-1 Infection Is Rescued by
      Modulating Actin Polymerization.
AB  - CD4+ T cell repopulation of the gut is rarely achieved in HIV-1-infected
      individuals who are receiving clinically effective antiretroviral therapy.
      Alterations in the integrity of the mucosal barrier have been indicated as a
      cause for chronic immune activation and disease progression. In this study, we
      present evidence that persistent immune activation causes impairment of
      lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking
      from the blood stream to peripheral organs. CCR6+ and CXCR3+ Th cells accumulate
      in the blood of aviremic HIV-1-infected patients on long-term antiretroviral
      therapy, and their frequency in the circulation positively correlates to levels
      of soluble CD14 in plasma, a marker of chronic immune activation. Th cells show
      an impaired response to chemotactic stimuli both in humans and in the pathogenic
      model of SIV infection, and this defect is due to hyperactivation of cofilin and
      inefficient actin polymerization. Taking advantage of a murine model of chronic
      immune activation, we demonstrate that cytoskeleton remodeling, induced by
      okadaic acid, restores lymphocyte migration in response to chemokines, both in
      vitro and in vivo. This study calls for novel pharmacological approaches in those
      pathological conditions characterized by persistent immune activation and loss of
      trafficking of T cell subsets to niches that sustain their maturation and
      activities.

PMID- 27895172
TI  - Pulmonary Dendritic Cell Subsets Shape the Respiratory Syncytial Virus-Specific
      CD8+ T Cell Immunodominance Hierarchy in Neonates.
AB  - Young infants are generally more susceptible to viral infections and experience
      more severe disease than do adults. CD8+ T cells are important for viral
      clearance, and although often ineffective in neonates they can be protective when
      adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory
      syncytial virus (RSV) infection, we previously demonstrated that the CD8+ T cell
      immunodominance hierarchy to two RSV-derived epitopes, KdM282-90 and DbM187-195,
      was determined by the age at infection. To determine whether age-dependent RSV
      specific CD8+ T cell responses could be modified through enhanced innate
      signaling, we used TLR4 or TLR9 agonist treatment at the time of infection, which
      remarkably changed the neonatal codominant response to an adult-like KdM282-90
      CD8+ T cell immunodominant response. This shift was associated with an increase
      in the number of conventional dendritic cells, CD11b+ and CD103+ dendritic cells,
      in the lung-draining lymph node, as well as increased expression of the
      costimulatory molecule CD86. The magnitude of the KdM282-90 CD8+ T cell response
      in TLR agonist-treated neonates could be blocked with Abs against CD80 and CD86.
      These studies demonstrate the age-dependent function of conventional dendritic
      cells, their role in determining immunodominance hierarchy, and epitope-specific
      CD8+ T cell requirements for costimulation, all of which influence the immune
      response magnitude. The unique impact of TLR agonists on neonatal T cell
      responses is important to consider for RSV vaccines designed for young infants.

PMID- 27895173
TI  - Human Regulatory T Cells Mediate Transcriptional Modulation of Dendritic Cell
      Function.
AB  - Regulatory T cells (Treg) attenuate dendritic cell (DC) maturation and
      stimulatory function. Current knowledge on the functional impact of semimature DC
      is limited to CD4+ T cell proliferation and cytokine production. Little is known
      about the molecular basis underpinning the functional effects of Treg-treated DC
      (Treg-DC). We present novel evidence that Treg-DC skewed CD4+ naive T cell
      polarization toward a regulatory phenotype and impaired CD8+ T cell allo-reactive
      responses, including their ability to induce target tissue damage in a unique in
      vitro human graft-versus-host disease skin explant model. Microarray analysis
      clustered Treg-DC as a discrete population from mature-DC and immature-DC, with
      51 and 93 genes that were significantly over- or underexpressed, respectively,
      compared with mature-DC. Quantitative real-time PCR analysis revealed an
      intermediate expression level of CD38, CD83, CD80 and CD86 mRNA in Treg-DC, lower
      than mature-DC, higher than immature-DC. We also observed an attenuation of NF
      kappaB pathway, an upstream regulator of the aforementioned genes, concomitant
      with reduced expression of two NF-kappaB-signaling related genes RELB and
      NFkappaBIZ, in the Treg-DC, together with an increased expression of Wnt5a, a
      negative regulator of DC differentiation. We further confirmed that the Treg-DC
      mediated skewed CD4+ naive T cell polarization resulted from decreased IL-12
      secretion by Treg-DC, which may be post-transcriptionally modulated by decreased
      expression of microRNA-155 in Treg-DC. To our knowledge, this is the first study
      demonstrating a transcriptional modulation of DC function by human Treg,
      partially via attenuation of the NF-kappaB signaling pathway and upregulation of
      Wnt5a, suggesting Treg may interfere with DC reprogramming during maturation,
      thereby modulating DC function.

PMID- 27895174
TI  - Human Lung Fibroblasts Present Bacterial Antigens to Autologous Lung Th Cells.
AB  - Lung fibroblasts are key structural cells that reside in the submucosa where they
      are in contact with large numbers of CD4+ Th cells. During severe viral infection
      and chronic inflammation, the submucosa is susceptible to bacterial invasion by
      lung microbiota such as nontypeable Haemophilus influenzae (NTHi). Given their
      proximity in tissue, we hypothesized that human lung fibroblasts play an
      important role in modulating Th cell responses to NTHi. We demonstrate that
      fibroblasts express the critical CD4+ T cell Ag-presentation molecule HLA-DR
      within the human lung, and that this expression can be recapitulated in vitro in
      response to IFN-gamma. Furthermore, we observed that cultured lung fibroblasts
      could internalize live NTHi. Although unable to express CD80 and CD86 in response
      to stimulation, fibroblasts expressed the costimulatory molecules 4-1BBL, OX-40L,
      and CD70, all of which are related to memory T cell activation and maintenance.
      CD4+ T cells isolated from the lung were predominantly (mean 97.5%) CD45RO+
      memory cells. Finally, cultured fibroblasts activated IFN-gamma and IL-17A
      cytokine production by autologous, NTHi-specific lung CD4+ T cells, and cytokine
      production was inhibited by a HLA-DR blocking Ab. These results indicate a novel
      role for human lung fibroblasts in contributing to responses against bacterial
      infection through activation of bacteria-specific CD4+ T cells.

PMID- 27895175
TI  - Platelets Mediate Host Defense against Staphylococcus aureus through Direct
      Bactericidal Activity and by Enhancing Macrophage Activities.
AB  - Platelets are the chief effector cells in hemostasis. However, recent evidence
      suggests they have multiple roles in host defense against infection. Reports by
      us and others showed that platelets functionally contribute to protection against
      Staphylococcus aureus infection. In the current study, the capacity of mouse
      platelets to participate in host defense against S. aureus infection was
      determined by assessing two possibilities. First, we determined the ability of
      platelets to kill S. aureus directly; and, second, we tested the possibility that
      platelets enhance macrophage phagocytosis and intracellular killing of S. aureus
      In this study we report evidence in support of both mechanisms. Platelets
      effectively killed two different strains of S. aureus. A clinical isolate of
      methicillin-resistant S. aureus was killed by platelets (>40% killing in 2 h) in
      a thrombin-dependent manner whereas a methicillin-sensitive strain was killed to
      equal extent but did not require thrombin. Interestingly, thrombin-stimulated
      platelets also significantly enhanced peritoneal macrophage phagocytosis of both
      methicillin-resistant S. aureus and methicillin-sensitive S. aureus by >70%, and
      restricted intracellular growth by >40%. Enhancement of macrophage anti-S. aureus
      activities is independent of contact with platelets but is mediated through
      releasable products, namely IL-1beta. These data confirm our hypothesis that
      platelets participate in host defense against S. aureus both through direct
      killing of S. aureus and enhancing the antimicrobial function of macrophages in
      protection against S. aureus infection.

PMID- 27895177
TI  - OX40 Cooperates with ICOS To Amplify Follicular Th Cell Development and Germinal
      Center Reactions during Infection.
AB  - Cognate interactions between T follicular helper (Tfh) cells and B cells are
      essential for promoting protective Ab responses. Whereas costimulatory receptors
      such as ICOS are accepted as being important for the induction of Tfh cell fate
      decision, other molecules may play key roles in amplifying or maintaining the Tfh
      phenotype. In this study, with vaccinia virus infection in mice, we show that
      OX40 was expressed on Tfh cells that accumulated at the T/B borders in the white
      pulp of the spleen and that OX40-dependent signals directly shaped the magnitude
      and quality of the their response to viral Ags. OX40 deficiency in Tfh cells
      profoundly impaired the acquisition of germinal center (GC) B cell phenotype,
      plasma cell generation, and virus-specific Ab responses. Most significantly, we
      found that sustained interactions between OX40 and its ligand, OX40L, beyond the
      time of initial encounter with dendritic cells were required for the persistence
      of high numbers of Tfh and GC B cells. Interestingly, OX40 was coexpressed with
      ICOS on Tfh cells in and around the GC, and ICOS-ICOSL interactions were
      similarly crucial at late times for maintenance of the Tfh and GC B cells. Thus,
      OX40 and ICOS act in a cooperative, nonredundant manner to maximize and prolong
      the Tfh response that is generated after acute virus infection.

PMID- 27895176
TI  - The Syk-NFAT-IL-2 Pathway in Dendritic Cells Is Required for Optimal Sterile
      Immunity Elicited by Alum Adjuvants.
AB  - Despite a long history and extensive usage of insoluble aluminum salts (alum) as
      vaccine adjuvants, the molecular mechanisms underpinning Ag-specific immunity
      upon vaccination remain unclear. Dendritic cells (DCs) are crucial initiators of
      immune responses, but little is known about the molecular pathways used by DCs to
      sense alum and, in turn, activate T and B cells. In this article, we show that
      alum adjuvanticity requires IL-2 specifically released by DCs, even when T cell
      secretion of IL-2 is intact. We demonstrate that alum, as well as other sterile
      particulates, such as uric acid crystals, induces DCs to produce IL-2 following
      initiation of actin-mediated phagocytosis that leads to Src and Syk kinase
      activation, Ca2+ mobilization, and calcineurin-dependent activation of NFAT, the
      master transcription factor regulating IL-2 expression. Using chimeric mice, we
      show that DC-derived IL-2 is required for maximal Ag-specific proliferation of
      CD4+ T cells and optimal humoral responses following alum-adjuvanted
      immunization. These data identify DC-derived IL-2 as a key mediator of alum
      adjuvanticity in vivo and the Src-Syk pathway as a potential leverage point in
      the rational design of novel adjuvants.

PMID- 27895178
TI  - Conserved Region C Functions To Regulate PD-1 Expression and Subsequent CD8 T
      Cell Memory.
AB  - Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion
      during chronic Ag exposure. During acute infections, PD-1 is transiently
      expressed and has the potential to modulate CD8 T cell memory formation.
      Conserved region C (CR-C), a promoter proximal cis-regulatory element that is
      critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-kappaB
      signaling pathways. Here, a CR-C knockout mouse was established to determine its
      role on PD-1 expression and the corresponding effects on T cell function in vivo.
      Deletion of CR-C decreased PD-1 expression on CD4 T cells and Ag-specific CD8 T
      cells during acute and chronic lymphocytic choriomeningitis virus challenges, but
      did not affect the ability to clear an infection. Following acute lymphocytic
      choriomeningitis virus infection, memory CD8 T cells in the CR-C knockout mouse
      were formed in greater numbers, were more functional, and were more effective at
      responding to a melanoma tumor than wild-type memory cells. These data implicate
      a critical role for CR-C in governing PD-1 expression, and a subsequent role in
      guiding CD8 T cell differentiation. The data suggest the possibility that
      titrating PD-1 expression during CD8 T cell activation could have important
      ramifications in vaccine development and clinical care.

PMID- 27895179
TI  - Thymic Dendritic Cell Subsets Display Distinct Efficiencies and Mechanisms of
      Intercellular MHC Transfer.
AB  - Thymic dendritic cells (DC) delete self-antigen-specific thymocytes, and drive
      development of Foxp3-expressing immunoregulatory T cells. Unlike medullary thymic
      epithelial cells, which express and present peripheral self-antigen, DC must
      acquire self-antigen to mediate thymic negative selection. One such mechanism
      entails the transfer of surface MHC-self peptide complexes from medullary thymic
      epithelial cells to thymic DC. Despite the importance of thymic DC cross-dressing
      in negative selection, the factors that regulate the process and the capacity of
      different thymic DC subsets to acquire MHC and stimulate thymocytes are poorly
      understood. In this study intercellular MHC transfer by thymic DC subsets was
      investigated using an MHC-mismatch-based in vitro system. Thymic conventional DC
      (cDC) subsets signal regulatory protein alpha (SIRPalpha+) and CD8alpha+ readily
      acquired MHC class I and II from thymic epithelial cells but plasmacytoid DC were
      less efficient. Intercellular MHC transfer was donor-cell specific; thymic DC
      readily acquired MHC from TEC plus thymic or splenic DC, whereas thymic or
      splenic B cells were poor donors. Furthermore DC origin influenced cross
      dressing; thymic versus splenic DC exhibited an increased capacity to capture TEC
      derived MHC, which correlated with direct expression of EpCAM by DC. Despite
      similar capacities to acquire MHC-peptide complexes, thymic CD8alpha+ cDC
      elicited increased T cell stimulation relative to SIRPalpha+ cDC. DC cross
      dressing was cell-contact dependent and unaffected by lipid raft disruption of
      donor TEC. Furthermore, blocking PI3K signaling reduced MHC acquisition by thymic
      CD8alpha+ cDC and plasmacytoid DC but not SIRPalpha+ cDC. These findings
      demonstrate that multiple parameters influence the efficiency of and distinct
      mechanisms drive intercellular MHC transfer by thymic DC subsets.

PMID- 27895182
TI  - Recognizing the Top 25 Peer Reviewers for the Journal of Virology.

PMID- 27895180
TI  - Regulatory T Cells Promote Myositis and Muscle Damage in Toxoplasma gondii
      Infection.
AB  - The coordination of macrophage polarization is essential for the robust
      regenerative potential of skeletal muscle. Repair begins with a phase mediated by
      inflammatory monocytes (IM) and proinflammatory macrophages (M1), followed by
      polarization to a proregenerative macrophage (M2) phenotype. Recently, regulatory
      T cells (Tregs) were described as necessary for this M1 to M2 transition. We
      report that chronic infection with the protozoan parasite Toxoplasma gondii
      causes a nonresolving Th1 myositis with prolonged tissue damage associated with
      persistent M1 accumulation. Surprisingly, Treg ablation during chronic infection
      rescues macrophage homeostasis and skeletal muscle fiber regeneration, showing
      that Tregs can directly contribute to muscle damage. This study provides evidence
      that the tissue environment established by the parasite could lead to a
      paradoxical pathogenic role for Tregs. As such, these findings should be
      considered when tailoring therapies directed at Tregs in inflammatory settings.

PMID- 27895185
TI  - Correction for Abrisch et al., Infection by Herpes Simplex Virus 1 Causes Near
      Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome.

PMID- 27895186
TI  - Correction for Eduardo-Correia et al., ISG15 Is Counteracted by Vaccinia Virus E3
      Protein and Controls the Proinflammatory Response against Viral Infection.

PMID- 27895181
TI  - Complement Protein C1q Enhances Macrophage Foam Cell Survival and Efferocytosis.
AB  - In the atherosclerotic lesion, macrophages ingest high levels of damaged modified
      low-density lipoproteins (LDLs), generating macrophage foam cells. Foam cells
      undergo apoptosis and, if not efficiently cleared by efferocytosis, can undergo
      secondary necrosis, leading to plaque instability and rupture. As a component of
      the innate immune complement cascade, C1q recognizes and opsonizes modified forms
      of LDL, such as oxidized or acetylated LDL, and promotes ingestion by macrophages
      in vitro. C1q was shown to be protective in an atherosclerosis model in vivo.
      Therefore, this study aimed to investigate whether ingestion of modified LDL in
      the presence of C1q alters macrophage foam cell survival or function. In an
      unbiased transcriptome analysis, C1q was shown to modulate expression of clusters
      of genes involved in cell death and apoptosis pathways in human monocyte-derived
      macrophages ingesting modified LDL; this was validated by quantitative PCR in
      human and murine macrophages. C1q downregulated levels and activity of active
      caspase-3 and PARP-1 in human and mouse macrophages during ingestion of modified
      LDL. This led to a measurable increase in survival and decrease in cell death, as
      measured by alamarBlue and propidium iodide assays, respectively. C1q
      opsonization also increased phagocytosis and efferocytosis in macrophage foam
      cells. These data suggest that C1q promotes macrophage survival during ingestion
      of excess cholesterol, as well as improves foam cell efferocytic function. This
      may be important in slowing disease progression and provides insight into the
      protective role of C1q in early atherosclerosis.

PMID- 27895187
TI  - Correction for Royo et al., Differential Induction of Apoptosis, Interferon
      Signaling, and Phagocytosis in Macrophages Infected with a Panel of Attenuated
      and Nonattenuated Poxviruses.

PMID- 27895188
TI  - Antisocial Alcoholism in Parents of Adolescents and Young Adults With Childhood
      ADHD.
AB  - OBJECTIVE: Test the hypothesis that alcoholism, including antisocial alcoholism,
      is more prevalent among mothers and fathers of children with versus without ADHD.
      METHOD: Mothers (312 ADHD group, 235 non-ADHD group) and fathers (291 ADHD group,
      227 non-ADHD group) in the Pittsburgh ADHD Longitudinal Study were interviewed
      along with their adolescent and young adult offspring. RESULTS: Maternal and
      paternal alcoholism, with and without comorbid antisociality, was more prevalent
      in the ADHD group. Paternal alcoholism without antisociality was only marginally
      higher for probands after controlling for paternal ADHD. Offspring conduct
      disorder comorbidity was associated with parental antisociality but not parental
      antisocial alcoholism. CONCLUSION: Our findings that 44% of proband fathers and
      25% of proband mothers experienced alcohol problems with or without antisociality
      are further evidence of increased alcoholism prevalence in families affected by
      ADHD. Maternal alcoholism and antisociality are prominent contributors to this
      family-level vulnerability. These findings indicate the need to assess long-term
      offspring outcomes as a function of parental alcohol and externalizing
      comorbidities, and perhaps other indicators of parental alcoholism phenotype, as
      familial vulnerability unfolds across development.

PMID- 27895189
TI  - How to do it: bedside ultrasound to assist lumbar puncture.
AB  - For many neurologists, lumbar puncture is the only practical procedure that they
      undertake on a regular basis. Although anaesthetists and emergency physicians
      routinely employ ultrasound to assist lumbar puncture, neurologists do not. In
      this article, we outline the technique that we use for an ultrasound-assisted
      lumbar puncture, together with the evidence base that suggests that ultrasound
      has significant benefits. We aim to raise awareness of a method that can make
      lumbar puncture more likely to succeed and to be more comfortable for the
      patient.

PMID- 27895191
TI  - Putative Mechanism of Salt-Dependent Neurogenic Hypertension: Cell-Autonomous
      Activation of Organum Vasculosum Laminae Terminalis Neurons by Hypernatremia.

PMID- 27895190
TI  - Caveolin-1 Deletion Prevents Hypertensive Vascular Remodeling Induced by
      Angiotensin II.
AB  - It has been proposed that membrane microdomains, caveolae, in vascular cells are
      critical for signal transduction and downstream functions induced by angiotensin
      II (AngII). We have tested our hypothesis that caveolin-1 (Cav1), a major
      structural protein of vascular caveolae, plays a critical role in the development
      of vascular remodeling by AngII via regulation of epidermal growth factor
      receptor and vascular endothelial adhesion molecule-1. Cav1-/- and control Cav+/+
      mice were infused with AngII for 2 weeks to induce vascular remodeling and
      hypertension. On AngII infusion, histological assessments demonstrated medial
      hypertrophy and perivascular fibrosis of aorta and coronary and renal arteries in
      Cav1+/+ mice compared with sham-operated Cav1+/+ mice. AngII-infused Cav1+/+ mice
      also showed a phenotype of cardiac hypertrophy with increased heart weight to
      body weight ratio compared with control Cav1+/+ mice. In contrast, Cav1-/- mice
      infused with AngII showed attenuation of vascular remodeling but not cardiac
      hypertrophy. Similar levels of AngII-induced hypertension were found in both
      Cav1+/+ and Cav1-/- mice as assessed by telemetry. In Cav1+/+ mice, AngII
      enhanced tyrosine-phosphorylated epidermal growth factor receptor staining in the
      aorta, which was attenuated in Cav1-/- mice infused with AngII. Enhanced Cav1 and
      vascular endothelial adhesion molecule-1 expression was also observed in aorta
      from AngII-infused Cav1+/+ mice but not in Cav1-/- aorta. Experiments with
      vascular cells further provided a potential mechanism for our in vivo findings.
      These data suggest that Cav1, and presumably caveolae, in vascular smooth muscle
      and the endothelium plays a critical role in vascular remodeling and inflammation
      independent of blood pressure or cardiac hypertrophy regulation.

PMID- 27895192
TI  - Development of Left Ventricular Hypertrophy in Treated Hypertensive Outpatients:
      The Campania Salute Network.
AB  - : There is little information on left ventricular (LV) hypertrophy (LVH)
      development during antihypertensive treatment. We evaluate incident LVH in a
      treated hypertensive cohort, the Campania Salute Network registry. We analyzed
      prospectively 4290 hypertensives (aged 50.3+/-11.1 years, 40% women) with at
      least 1-year follow-up, without LVH at baseline. Incident LVH was defined as the
      first detection of echocardiographic LV mass index >=47 in women or >=50 g/m2.7
      in men. During a median 48-month follow-up, 915 patients (21.3%) developed LVH.
      They were older, more frequently women, and obese (P<0.0001), with initial higher
      fasting glucose, diastolic and systolic blood pressure, LV mass index, lower
      heart rate and glomerular filtration rate, longer hypertension history and follow
      up, and higher average systolic blood pressure during follow-up (all P<0.05),
      despite a more frequent treatment with Ca++-channel blockers and diuretics (both
      P<0.02). At multivariable Cox regression, incident LVH was independently
      associated with older age, female sex, obesity, higher average systolic blood
      pressure during follow-up, and initial greater LV mass index (all P<0.02). By
      categorizing patients according to obesity and sex, obesity independently
      increased the risk for incident LVH in both sexes (obese versus nonobese men:
      hazard ratio, 1.34; confidence interval, 1.05-1.72; P=0.019; and obese versus
      nonobese women: hazard ratio, 1.34; confidence interval, 1.08-1.66; P=0.007).
      Despite more aggressive antihypertensive therapy, 21% of hypertensive patients
      develop clear-cut LVH. After adjusting for confounders, risk of incident LVH is
      particular relevant among women and is further increased by the presence of
      obesity. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT02211365.

PMID- 27895194
TI  - Systematic Characterization and Prediction of Human Hypertension Genes.
AB  - Hypertension is a major cardiovascular risk factor and accounts for a large part
      of cardiovascular mortality. In this work, we analyzed the properties of
      hypertension genes and found that when compared with genes not yet known to be
      involved in hypertension regulation, known hypertension genes display
      distinguishing features: (1) hypertension genes tend to be located at network
      center; (2) hypertension genes tend to interact with each other; and (3)
      hypertension genes tend to enrich in certain biological processes and show
      certain phenotypes. Based on these features, we developed a machine-learning
      algorithm to predict new hypertension genes. One hundred and seventy-seven
      candidates were predicted with a posterior probability >0.9. Evidence supporting
      17 of the predictions has been found.

PMID- 27895193
TI  - Organum Vasculosum of the Lamina Terminalis Detects NaCl to Elevate Sympathetic
      Nerve Activity and Blood Pressure.
AB  - High-salt diet elevates NaCl concentrations in the cerebrospinal fluid to
      increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. The
      organum vasculosum of the lamina terminalis (OVLT) resides along the rostral wall
      of the third ventricle, lacks a complete blood-brain barrier, and plays a pivotal
      role in body fluid homeostasis. Therefore, the present study used a multifaceted
      approach to examine whether OVLT neurons of Sprague-Dawley rats are intrinsically
      sensitive to changes in extracellular NaCl concentrations and mediate the
      sympathoexcitatory responses to central NaCl loading. Using in vitro whole-cell
      recordings, step-wise increases in extracellular NaCl concentrations (2.5-10
      mmol/L) produced concentration-dependent excitation of OVLT neurons.
      Additionally, these excitatory responses were intrinsic to OVLT neurons because
      hypertonic NaCl evoked inward currents, despite pharmacological synaptic
      blockade. In vivo single-unit recordings demonstrate that the majority of OVLT
      neurons (72%, 13/19) display concentration-dependent increases in neuronal
      discharge to intracarotid (50 MUL/15 s) or intracerebroventricular infusion (5
      MUL/10 minutes) of hypertonic NaCl. Microinjection of hypertonic NaCl (30 nL/60
      s) into the OVLT, but not adjacent areas, increased lumbar SNA, adrenal SNA, and
      arterial blood pressure in a concentration-dependent manner. Renal SNA decreased
      and splanchnic SNA remained unaffected. Finally, local inhibition of OVLT neurons
      with the GABAA receptor agonist muscimol (24 nL/10 s) significantly attenuated
      the sympathoexcitatory and pressor responses to intracerebroventricular infusion
      of 0.5 mol/L or 1.0 mol/L NaCl. Collectively, these findings indicate that OVLT
      neurons detect changes in extracellular NaCl concentrations to selectively alter
      SNA and raise arterial blood pressure.

PMID- 27895195
TI  - A 'Scottish Poor Law of Lunacy'? Poor Law, Lunacy Law and Scotland's parochial
      asylums.
AB  - Scotland's parochial asylums are unfamiliar institutional spaces. Representing
      the concrete manifestation of the collision between two spheres of legislation,
      the Poor Law and the Lunacy Law, six such asylums were constructed in the latter
      half of the nineteenth century. These sites expressed the enduring mandate of the
      Scottish Poor Law 1845 over the domain of 'madness'. They were institutions whose
      very existence was fashioned at the directive of the local arm of the Poor Law,
      the parochial board, and they constituted a continuing 'Scottish Poor Law of
      Lunacy'. Their origins and operation significantly subverted the intentions and
      objectives of the Lunacy Act 1857, the aim of which had been to institute a
      public district asylum network with nationwide coverage.

PMID- 27895196
TI  - From asylum to action in Scotland: the emergence of the Scottish Union of Mental
      Patients, 1971-2.
AB  - By analysing a collection of documents authored by Thomas Ritchie, founder of the
      Scottish Union of Mental Patients (SUMP), this study recounts the emergence of
      mental patient unionism at Hartwood Hospital, North Lanarkshire, Scotland. The
      discourse and action employed by Ritchie and SUMP are understood and situated in
      relation to intended audiences, social and material conditions of the asylum
      space, and transformations in cultures beyond the asylum, including nascent
      industrial strife, social liberalism, civil rights, the London 'underground' and
      counter-cultures.

PMID- 27895197
TI  - The Effect of ACE I/D Polymorphisms Alone and With Concomitant Risk Factors on
      Coronary Artery Disease.
AB  - BACKGROUND: Coronary artery disease (CAD), also known as atherosclerotic heart
      disease, is a leading cause of mortality and morbidity throughout the world. The
      role of insertion/deletion (I/D) polymorphisms of the angiotensin-converting
      enzyme (ACE) gene in the etiology of CAD remains to be more completely clarified.
      The aim of this study was to determine the role of the ACE I/D polymorphism in
      patients with CAD and to study the association together with traditional risk
      factors in assessing the risk of CAD. METHODS: Our study population included 145
      Tunisian patients with symptomatic CAD and a control group of 300 people matched
      for age and sex. All participants in the study were genotyped for the ACE I/D
      polymorphisms obtained by polymerase chain reaction amplification on genomic DNA.
      RESULTS: Our analysis showed that the ACE D allele frequency ( P < 10-3; odds
      ratio [OR] = 5.2; 95% confidence interval [CI] = 3.6-7.6) and DD genotype ( P <
      10-3; OR = 6.8; 95% CI = 4.4-10) are significantly more prevalent among patients
      with CAD than in controls and may be predisposing to CAD. We further found that
      the risk of CAD is greatly potentiated by several concomitant risk factors
      (smoking, diabetes, hypertension, dyslipidemia, and a family history of CAD).
      CONCLUSION: The ACE D allele may be predictive in individuals who may be at risk
      of developing CAD. Further investigations of these polymorphisms and their
      possible synergisms with traditional risk factors for CAD could help to ascertain
      better predictability for CAD susceptibility.

PMID- 27895198
TI  - Autism and reactive attachment/disinhibited social engagement disorders: Co
      occurrence and differentiation.
AB  - DSM-5 ( Diagnostic and Statistical Manual of Mental Disorders, 5th edition)
      Reactive Attachment Disorder (RAD) and Disinhibited Social Engagement Disorder
      (DSED) are rare disorders sharing social difficulties with autism. The DSM-5 and
      ICD-10 (International Classification of Diseases, 10th revsion) state that
      RAD/DSED should not be diagnosed in children with autism. The purpose of our
      study is to determine whether children can meet criteria for both autism and
      RAD/DSED and to identify specific symptoms discriminating the disorders. Subjects
      were 486 children with autism and no RAD/DSED and 20 with RAD/DSED, 4-17 years of
      age. In total, 13 children with RAD/DSED met criteria for autism. Using the
      Checklist for Autism Spectrum Disorder (CASD), there was no overlap in total
      scores between the RAD/DSED with autism group (score range = 15-27) versus the
      RAD/DSED without autism group (range = 7-10 ). The autism with and without
      RAD/DSED groups did not differ in CASD scores. Nine of the CASD autism symptoms
      were found only in the autism with and without RAD/DSED groups. Our study
      demonstrates that children can meet criteria for both autism and RAD/DSED and
      that the disorders are easily differentiated by the presence of specific autism
      symptoms. Autism is a neurogenetic disorder, and RAD/DSED results from severe
      social-emotional maltreatment. Given the different etiologies, there is no reason
      why a child cannot have both disorders.

PMID- 27895200
TI  - Demographics, Mechanisms of Injury, and Concurrent Injuries Associated With
      Calcaneus Fractures: A Study of 14 516 Patients in the American College of
      Surgeons National Trauma Data Bank.
AB  - BACKGROUND: This study uses the American College of Surgeons National Trauma Data
      Bank (NTDB) to update the field on the demographics, injury mechanisms, and
      concurrent injuries among a national sample of patients admitted to the hospital
      department with calcaneus fractures. METHODS: Patients with calcaneus fractures
      in the NTDB during 2011-2012 were identified and assessed. RESULTS: A total of 14
      516 patients with calcaneus fractures were included. The most common comorbidity
      was hypertension (18%), and more than 90% of fractures occurred via traffic
      accident (49%) or fall (43%). A total of 11 137 patients had concurrent injuries.
      Associated lower extremity fractures had the highest incidence and occurred in
      61% of patients (of which the most common were other foot and ankle fractures).
      Concurrent spine fractures occurred in 23% of patients (of which the most common
      were lumbar spine fractures). Concurrent nonorthopaedic injuries included head
      injuries in 18% of patients and thoracic organ injuries in 15% of patients.
      CONCLUSION: This national sample indicates that associated injuries occur in more
      than three quarters calcaneus fracture patients. The most common associated
      fractures are in close proximity to the calcaneus. Although the well-defined
      association of calcaneus fractures with lumbar spine fractures was identified,
      the data presented highlight additional strong associations of calcaneus
      fractures with other orthopaedic and nonorthopaedic injuries. LEVELS OF EVIDENCE:
      Prognostic, Level III: Retrospective review of a prospectively collected cohort.

PMID- 27895201
TI  - Intraorbital wooden foreign body detected by computed tomography and magnetic
      resonance imaging.
AB  - To identify and localize an intraorbital wooden foreign body is often a
      challenging radiological issue; delayed diagnosis can lead to serious adverse
      complications. Preliminary radiographic interpretations are often integrated with
      computed tomography and magnetic resonance, which play a crucial role in reaching
      the correct definitive diagnosis. We report on a 40 years old male complaining of
      pain in the right orbit referred to our hospital for evaluation of eyeball pain
      and double vision with an unclear clinical history. Computed tomography and
      magnetic resonance scans supposed the presence of an abscess caused by a foreign
      intraorbital body, confirmed by surgical findings.

PMID- 27895202
TI  - The LBD12-1 Transcription Factor Suppresses Apical Meristem Size by Repressing
      Argonaute 10 Expression.
AB  - The shoot apical meristem (SAM) consists of a population of multipotent cells
      that generates all aerial structures and regenerates itself. SAM maintenance and
      lateral organ development are regulated by several complex signaling pathways, in
      which the Argonaute gene-mediated pathway plays a key role. One Argonaute gene,
      AGO10, functions as a microRNA locker that attenuates miR165/166 activity and
      positively regulates shoot apical meristem development, but little is known about
      when and how AGO10 is regulated at the transcriptional level. In this work, we
      showed that transgenic rice plants overexpressing LBD12-1, an LBD family
      transcription factor, exhibited stunted growth, twisted leaves, abnormal anthers,
      and reduced SAM size. Further research revealed that LBD12-1 directly binds to
      the promoter region and represses the expression of AGO10. Overexpression of
      AGO10 in an LBD12-1 overexpression background rescued the growth defect phenotype
      of LBD12-1-overexpressing plants. The expression of LBD12-1 and its binding
      ability to the AGO10 promoter is induced by stress. lbd12-1 loss-of-function
      mutants showed similar phenotypes and SAM size to the wild type under normal
      conditions, but lbd12-1 had a larger SAM under salt stress. Our findings provide
      novel insights into the regulatory mechanism of AGO10 by which SAM size is
      controlled under stress conditions.

PMID- 27895203
TI  - A Palmitic Acid Elongase Affects Eicosapentaenoic Acid and Plastidial
      Monogalactosyldiacylglycerol Levels in Nannochloropsis.
AB  - Nannochloropsis species are oleaginous eukaryotes containing a plastid limited by
      four membranes, deriving from a secondary endosymbiosis. In Nannochloropsis,
      thylakoid lipids, including monogalactosyldiacylglycerol (MGDG), are enriched in
      eicosapentaenoic acid (EPA). The need for EPA in MGDG is not understood. Fatty
      acids are de novo synthesized in the stroma, then converted into very-long-chain
      polyunsaturated fatty acids (FAs) at the endoplasmic reticulum (ER). The
      production of MGDG relies therefore on an EPA supply from the ER to the plastid,
      following an unknown process. We identified seven elongases and five desaturases
      possibly involved in EPA production in Nannochloropsis gaditana Among the six
      heterokont-specific saturated FA elongases possibly acting upstream in this
      pathway, we characterized the highly expressed isoform Delta0-ELO1 Heterologous
      expression in yeast (Saccharomyces cerevisiae) showed that NgDelta0-ELO1 could
      elongate palmitic acid. Nannochloropsis Delta0-elo1 mutants exhibited a reduced
      EPA level and a specific decrease in MGDG In NgDelta0-elo1 lines, the impairment
      of photosynthesis is consistent with a role of EPA-rich MGDG in nonphotochemical
      quenching control, possibly providing an appropriate MGDG platform for the
      xanthophyll cycle. Concomitantly with MGDG decrease, the level of triacylglycerol
      (TAG) containing medium chain FAs increased. In Nannochloropsis, part of EPA used
      for MGDG production is therefore biosynthesized by a channeled process initiated
      at the elongation step of palmitic acid by Delta0-ELO1, thus acting as a
      committing enzyme for galactolipid production. Based on the MGDG/TAG balance
      controlled by Delta0-ELO1, this study also provides novel prospects for the
      engineering of oleaginous microalgae for biotechnological applications.

PMID- 27895204
TI  - Two h-Type Thioredoxins Interact with the E2 Ubiquitin Conjugase PHO2 to Fine
      Tune Phosphate Homeostasis in Rice.
AB  - Phosphate overaccumulator2 (PHO2) encodes a ubiquitin-conjugating E2 enzyme that
      is a major negative regulator of the inorganic phosphate (Pi)-starvation response
      signaling pathway. A yeast two-hybrid (Y2H) screen in rice (Oryza sativa; Os)
      using OsPHO2 as bait revealed an interaction between OsPHO2 and two h-type
      thioredoxins, OsTrxh1 and OsTrxh4. These interactions were confirmed in vivo
      using bimolecular fluorescence complementation (BiFC) of OsPHO2 and OsTrxh1/h4 in
      rice protoplasts and by in vitro pull-down assays with 6His-tagged OsTrxh1/h4 and
      GST-tagged OsPHO2. Y2H assays revealed that amino acid Cys-445 of OsPHO2 and an N
      terminal Cys in the "WCGPC" motif of Trxhs were required for the interaction.
      Split-ubiquitin Y2H analyses and BiFC assays in rice protoplasts confirmed the
      interaction of OsPHO2 with PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (OsPHF1),
      and PHOSPHATE1;2 (OsPHO1;2) in the endoplasmic reticulum and Golgi membrane
      system, where OsPHO2 mediates the degradation of OsPHF1 in both tobacco
      (Nicotiana benthamiana) leaves and rice seedlings. Characterization of rice pho2
      complemented lines, transformed with an endogenous genomic OsPHO2 or OsPHO2C445S
      (a constitutively reduced form) fragment, indicated that OsPHO2C445S restored Pi
      concentration in rice to statistically significant lower levels compared to
      native OsPHO2 Moreover, the suppression of OsTrxh1 (knockdown and knockout)
      resulted in slightly higher Pi concentration than that of wild-type Nipponbare in
      leaves. These results demonstrate that OsPHO2 is under redox control by
      thioredoxins, which fine-tune its activity and link Pi homeostasis with redox
      balance in rice.

PMID- 27895205
TI  - Hybridization in Plants: Old Ideas, New Techniques.
AB  - Hybridization has played an important role in the evolution of many lineages.
      With the growing availability of genomic tools and advancements in genomic
      analyses, it is becoming increasingly clear that gene flow between divergent taxa
      can generate new phenotypic diversity, allow for adaptation to novel
      environments, and contribute to speciation. Hybridization can have immediate
      phenotypic consequences through the expression of hybrid vigor. On longer
      evolutionary time scales, hybridization can lead to local adaption through the
      introgression of novel alleles and transgressive segregation and, in some cases,
      result in the formation of new hybrid species. Studying both the abundance and
      the evolutionary consequences of hybridization has deep historical roots in plant
      biology. Many of the hypotheses concerning how and why hybridization contributes
      to biological diversity currently being investigated were first proposed tens and
      even hundreds of years ago. In this Update, we discuss how new advancements in
      genomic and genetic tools are revolutionizing our ability to document the
      occurrence of and investigate the outcomes of hybridization in plants.

PMID- 27895206
TI  - Endosperm and Imprinting, Inextricably Linked.

PMID- 27895209
TI  - Holistic Nursing Simulation: A Concept Analysis.
AB  - Simulation as a technology and holistic nursing care as a philosophy are two
      components within nursing programs that have merged during the process of
      knowledge and skill acquisition in the care of the patients as whole beings.
      Simulation provides opportunities to apply knowledge and skill through the use of
      simulators, standardized patients, and virtual settings. Concerns with simulation
      have been raised regarding the integration of the nursing process and recognizing
      the totality of the human being. Though simulation is useful as a technology, the
      nursing profession places importance on patient care, drawing on knowledge,
      theories, and expertise to administer patient care. There is a need to promptly
      and comprehensively define the concept of holistic nursing simulation to provide
      consistency and a basis for quality application within nursing curricula. This
      concept analysis uses Walker and Avant's approach to define holistic nursing
      simulation by defining antecedents, consequences, and empirical referents. The
      concept of holism and the practice of holistic nursing incorporated into
      simulation require an analysis of the concept of holistic nursing simulation by
      developing a language and model to provide direction for educators in design and
      development of holistic nursing simulation.

PMID- 27895210
TI  - "Dr Google" will see you now - time trends in online searches on headache.

PMID- 27895208
TI  - Diurnal Solar Energy Conversion and Photoprotection in Rice Canopies.
AB  - Genetic improvement of photosynthetic performance of cereal crops and increasing
      the efficiency with which solar radiation is converted into biomass has recently
      become a major focus for crop physiologists and breeders. The pulse amplitude
      modulated chlorophyll fluorescence technique (PAM) allows quantitative leaf level
      monitoring of the utilization of energy for photochemical light conversion and
      photoprotection in natural environments, potentially over the entire crop
      lifecycle. Here, the diurnal relationship between electron transport rate (ETR)
      and irradiance was measured in five cultivars of rice (Oryza sativa) in canopy
      conditions with PAM fluorescence under natural solar radiation. This relationship
      differed substantially from that observed for conventional short term light
      response curves measured under controlled actinic light with the same leaves.
      This difference was characterized by a reduced curvature factor when curve
      fitting was used to model this diurnal response. The engagement of
      photoprotective processes in chloroplast electron transport in leaves under
      canopy solar radiation was shown to be a major contributor to this difference.
      Genotypic variation in the irradiance at which energy flux into photoprotective
      dissipation became greater than ETR was observed. Cultivars capable of higher ETR
      at midrange light intensities were shown to produce greater leaf area over time,
      estimated by noninvasive imaging.

PMID- 27895219
TI  - Primer in Genetics and Genomics, Article 1: DNA, Genes, and Chromosomes.
AB  - Precision medicine refers to the practice of determining a patient's unique
      genetic, biomarker, and other characteristics for the purpose of improving his or
      her clinical outcomes. Not all patients with the same clinical diagnosis respond
      equally to identical treatment regimens. By examining patients at the molecular
      level, health-care providers will be better able to apply the most effective
      therapies that each individual requires. To understand precision medicine, nurses
      must have a solid understanding of genomics and proteomics. The purpose of this
      article is to (1) provide a historical review of what and how we have learned
      about the genome, particularly in the past century, (2) explain the processes
      whereby genetic information in cellular DNA is transcribed to messenger RNA and
      translated to protein, and (3) introduce genetic and epigenetic mechanisms that
      regulate gene expression.

PMID- 27895211
TI  - Improvement in aerobic capacity during cardiac rehabilitation in coronary artery
      disease patients: Is there a role for autonomic adaptations?
AB  - Background It has been previously shown in patients with heart failure that
      exercise-based rehabilitation programmes may improve functional capacity and
      autonomic response. The aim of this study was to investigate this issue further
      by evaluating whether an association exists between autonomic adaptations and
      improvements of aerobic capacity in a general population of coronary artery
      disease patients undergoing cardiac rehabilitation. Methods Ninety consecutive
      patients (age 60 +/- 11 years) attended a rehabilitation programme of moderate
      continuous training (25 +/- 8 sessions, 2-3 sessions/week). Functional capacity
      expressed as oxygen uptake (peak VO2) and autonomic function expressed as
      chronotropic response and heart rate recovery were evaluated by cardiopulmonary
      exercise tests before and after the rehabilitation programme. According to the
      expected mean increase in functional capacity, coronary artery disease patients
      were divided into two groups: those who improved peak VO2 by more than 2.6
      ml/kg/min (R group) and those who did not (NR group). Effects of the
      rehabilitation programme were compared in R and NR groups. Results The number and
      intensity of exercise sessions did not differ between R ( N = 39) and NR ( N =
      51) groups. However, only R patients improved chronotropic response (R: from 45.1
      +/- 16.9% to 72.7 +/- 34.1%, P < 0.01; NR: from 49.3 +/- 18.6% to 48.2 +/- 36.5%,
      P = NS) and heart rate recovery (R: from 16.9 +/- 7.0 bpm to 21.0 +/- 8.7 bpm, P
      < 0.01; NR: from 15.2 +/- 9.9 bpm to 15.8 +/- 8.5 bpm, P = NS). After training
      both chronotropic response and heart rate recovery were significantly higher in R
      than NR patients. Conclusions The improvement in aerobic capacity of coronary
      artery disease patients following exercise-based cardiac rehabilitation
      programmes is associated with positive adaptations of autonomic function.

PMID- 27895218
TI  - A New Approach to Identify High Burnout Medical Staffs by Kernel K-Means Cluster
      Analysis in a Regional Teaching Hospital in Taiwan.
AB  - This study uses kernel k-means cluster analysis to identify medical staffs with
      high burnout. The data collected in October to November 2014 are from the
      emotional exhaustion dimension of the Chinese version of Safety Attitudes
      Questionnaire in a regional teaching hospital in Taiwan. The number of effective
      questionnaires including the entire staffs such as physicians, nurses,
      technicians, pharmacists, medical administrators, and respiratory therapists is
      680. The results show that 8 clusters are generated by kernel k-means method.
      Employees in clusters 1, 4, and 5 are relatively in good conditions, whereas
      employees in clusters 2, 3, 6, 7, and 8 need to be closely monitored from time to
      time because they have relatively higher degree of burnout. When employees with
      higher degree of burnout are identified, the hospital management can take actions
      to improve the resilience, reduce the potential medical errors, and, eventually,
      enhance the patient safety. This study also suggests that the hospital management
      needs to keep track of medical staffs' fatigue conditions and provide timely
      assistance for burnout recovery through employee assistance programs, mindfulness
      based stress reduction programs, positivity currency buildup, and forming
      appreciative inquiry groups.

PMID- 27895221
TI  - CORRECTION.

PMID- 27895220
TI  - Patient perspectives on the barriers associated with medication adherence to oral
      chemotherapy.
AB  - Purpose Appropriate use of oral chemotherapy is a challenge for patients and
      clinicians. The purpose of this study was to analyze cancer patients' use of oral
      chemotherapies and identify opportunities to improve adherence. Methods We
      developed a 30-question survey to address frequency and reasons for
      reducing/skipping doses; sources of information for oral chemotherapy use;
      perceived importance of food-drug effects; and ease of understanding labeling
      directions. Results Ninety-three patients taking oral chemotherapies with chronic
      myeloid leukemia, renal cell carcinoma, breast cancer, and colorectal cancer
      completed the survey. This was a well-educated population with 69% (n = 62)
      having completed some college; 51% (n = 47) female and 59% (n = 54) older than 50
      years of age. Thirty percent of patients reported forgetting to take their oral
      chemotherapy at least "sometimes". Younger patients (<50 vs. >=50, p = 0.002),
      shorter treatment duration (<6 vs. >=6 months p = 0.03), or with chronic myeloid
      leukemia (vs. other diagnoses, p = 0.015) forget to take their oral chemotherapy
      at higher rates. Twenty-three percent (n = 21) indicated they intentionally
      skipped their oral chemotherapies and 38% (n = 8) of those did not inform their
      physicians. Forty-one percent (n = 28) taking drugs with significant food-drug
      effects did not think about their last meal before taking their oral chemotherapy
      and 80% (n = 55) did not understand the potential interactions. Additionally, 39%
      (n = 36/92) never looked at labeling and 15% (n = 14/91) had difficulty
      understanding label directions. Conclusion There are three main barriers
      associated with appropriate use of oral chemotherapies: misunderstanding about
      the timing of drug with food; stopping drug without informing physicians; and
      difficulty understanding labeling directions. A multipronged approach is needed
      to optimize communication of directions for optimal oral chemotherapy use.

PMID- 27895207
TI  - Signaling with Ions: The Keystone for Apical Cell Growth and Morphogenesis in
      Pollen Tubes.

PMID- 27895222
TI  - CORRECTION.

PMID- 27895223
TI  - RETRACTION.

PMID- 27895224
TI  - NKD Transcription Factors Are Central Regulators of Maize Endosperm Development.
AB  - NAKED ENDOSPERM1 (NKD1) and NKD2 are duplicate INDETERMINATE DOMAIN (IDD)
      transcription factors important for maize (Zea mays) endosperm development. RNA
      seq analysis of the nkd1 nkd2 mutant endosperm revealed that NKD1 and NKD2
      influence 6.4% of the transcriptome in developing aleurone and 6.7% in starchy
      endosperm. Processes regulated by NKD1 and NKD2 include gene expression,
      epigenetic functions, cell growth and division, hormone pathways, and resource
      reserve deposition. The NKD1 and NKD2 proteins bind a consensus DNA sequence of
      TTGTCGT with slightly different properties. This motif was enriched in the
      promoters of gene transcripts differentially expressed (DE) in mutant endosperm.
      DE genes with a NKD binding motif in the 5' promoter region were considered as
      likely direct targets of NKD1 and NKD2 regulation, and these putative direct
      target genes were notably enriched for storage proteins. Transcription assays
      demonstrate that NKD1 and NKD2 can directly regulate gene transcription,
      including activation of opaque2 and viviparous1 promoters. NKD2 functions as a
      negative regulator of nkd1 transcription, consistent with previously reported
      feedback regulation. NKD1 and NKD2 can homo- and heterodimerize through their ID
      domains. These analyses implicate NKD1 and NKD2 as central regulators of gene
      expression in developing maize endosperm.

PMID- 27895225
TI  - Loss of Inositol Phosphorylceramide Sphingolipid Mannosylation Induces Plant
      Immune Responses and Reduces Cellulose Content in Arabidopsis.
AB  - Glycosylinositol phosphorylceramides (GIPCs) are a class of glycosylated
      sphingolipids found in plants, fungi, and protozoa. These lipids are abundant in
      the plant plasma membrane, forming ~25% of total plasma membrane lipids. Little
      is known about the function of the glycosylated headgroup, but two recent studies
      have indicated that they play a key role in plant signaling and defense. Here, we
      show that a member of glycosyltransferase family 64, previously named ECTOPICALLY
      PARTING CELLS1, is likely a Golgi-localized GIPC-specific mannosyl-transferase,
      which we renamed GIPC MANNOSYL-TRANSFERASE1 (GMT1). Sphingolipid analysis
      revealed that the Arabidopsis thaliana gmt1 mutant almost completely lacks
      mannose-carrying GIPCs. Heterologous expression of GMT1 in Saccharomyces
      cerevisiae and tobacco (Nicotiana tabacum) cv Bright Yellow 2 resulted in the
      production of non-native mannosylated GIPCs. gmt1 displays a severe dwarfed
      phenotype and a constitutive hypersensitive response characterized by elevated
      salicylic acid and hydrogen peroxide levels, similar to that we previously
      reported for the Golgi-localized, GIPC-specific, GDP-Man transporter GONST1
      (Mortimer et al., 2013). Unexpectedly, we show that gmt1 cell walls have a
      reduction in cellulose content, although other matrix polysaccharides are
      unchanged.

PMID- 27895226
TI  - The Plastoglobule-Localized Metallopeptidase PGM48 Is a Positive Regulator of
      Senescence in Arabidopsis thaliana.
AB  - Plastoglobuli (PG) are thylakoid-associated monolayer lipid particles with a
      specific proteome of ~30 PG core proteins and isoprenoid and neutral lipids.
      During senescence, PGs increase in size, reflecting their role in dismantling
      thylakoid membranes. Here, we show that the only PG-localized peptidase PGM48
      positively regulates leaf senescence. We discovered that PGM48 is a member of the
      M48 peptidase family with PGM48 homologs, forming a clade (M48D) only found in
      photosynthetic organisms. Unlike the M48A, B, and C clades, members of M48D have
      no transmembrane domains, consistent with their unique subcellular location in
      the PG. In vitro assays showed Zn-dependent proteolytic activity and substrate
      cleavage upstream of hydrophobic residues. Overexpression of PGM48 accelerated
      natural leaf senescence, whereas suppression delayed senescence. Quantitative
      proteomics of PG from senescing rosettes of PGM48 overexpression lines showed a
      dramatically reduced level of CAROTENOID CLEAVAGE ENZYME4 (CCD4) and
      significantly increased levels of the senescence-induced ABC1 KINASE7 (ABC1K7)
      and PHYTYL ESTER SYNTHASE1 (PES1). Yeast two-hybrid experiments identified PG
      core proteins ABC1K3, PES1, and CCD4 as PGM48 interactors, whereas several other
      PG-localized proteins and chlorophyll degradation enzymes did not interact. We
      discuss mechanisms through which PGM48 could possibly accelerate the senescence
      process.

PMID- 27895228
TI  - Differences in Durability, Dislodgement, and Other Complications With Use of Low
      Profile Nonballoon Gastrostomy Tubes in Children.
AB  - BACKGROUND: Nonballoon low-profile gastrostomy tubes (GTs) are used for enteral
      nutrition support in a subset of pediatric patients with feeding difficulties
      when use of balloon GTs is problematic. Different nonballoon low-profile tube
      types are available, but comparative studies are lacking. MATERIALS AND METHODS:
      This was a retrospective cohort study comparing complications and outcomes
      between different low-profile nonballoon GTs at a pediatric tertiary care center
      over 10 years. RESULTS: We identified 43 patients with 160 tube placement
      procedures, including 93 (58%) BARD tubes (type A) and 67 (42%) Mini-ONE tubes
      (type B). Accidental tube dislodgment occurred exclusively with type B (33% vs
      0%, P < .0001) with dislodgment occurring at a median of 54 days after placement.
      Type A GTs were more likely to be changed due to leakage (47% vs 8%, P < .0001).
      Minor gastrostomy site bleeding was more likely to be seen with type A tube
      changes (46% vs 7%, P < .0001). Patient sedation or site dilation was rarely
      needed in either group. Time to tube change was longer in the type B GTs (BARD) (
      P = .016) with a median tube survival in the type A and type B groups at 432 and
      284 days, respectively, with a hazard ratio of 1.89 (95% confidence interval, 1.2
      2.99), but once confounders were accounted for, the effect of tube type was no
      longer statistically significant. CONCLUSION: Our study shows that differences
      exist with use of various low-profile nonballoon GTs. This should be taken into
      consideration when counseling families about the most appropriate tube type for
      their children.

PMID- 27895227
TI  - Phosphorylation of ARF2 Relieves Its Repression of Transcription of the K+
      Transporter Gene HAK5 in Response to Low Potassium Stress.
AB  - Potassium (K+) plays crucial roles in plant growth and development. In natural
      environments, K+ availability in soils is relatively low and fluctuating.
      Transcriptional regulation of K+ transporter genes is one of the most important
      mechanisms in the plant's response to K+ deficiency. In this study, we
      demonstrated that the transcription factor ARF2 (Auxin Response Factor 2)
      modulates the expression of the K+ transporter gene HAK5 (High Affinity K+
      transporter 5) in Arabidopsis thaliana The arf2 mutant plants showed a tolerant
      phenotype similar to the HAK5-overexpressing lines on low-K+ medium, whose
      primary root lengths were longer than those of wild-type plants. High-affinity K+
      uptake was significantly increased in these plants. ARF2-overexpressing lines and
      the hak5 mutant were both sensitive to low-K+ stress. Disruption of HAK5 in the
      arf2 mutant abolished the low-K+-tolerant phenotype of arf2 As a transcriptional
      repressor, ARF2 directly bound to the HAK5 promoter and repressed HAK5 expression
      under K+ sufficient conditions. ARF2 can be phosphorylated after low-K+
      treatment, which abolished its DNA binding activity to the HAK5 promoter and
      relieved the inhibition on HAK5 transcription. Therefore, HAK5 transcript could
      be induced, and HAK5-mediated high-affinity K+ uptake was enhanced under K+
      deficient conditions. The presented results demonstrate that ARF2 plays important
      roles in the response to external K+ supply in Arabidopsis and regulates HAK5
      transcription accordingly.

PMID- 27895231
TI  - A year of guidelines: What have we learnt?

PMID- 27895229
TI  - Influence of PECAM-1 ligand interactions on PECAM-1-dependent cell motility and
      filopodia extension.
AB  - Platelet endothelial cell adhesion molecule (PECAM-1) has been implicated in
      angiogenesis through processes that involve stimulation of endothelial cell
      motility. Previous studies suggest that PECAM-1 tyrosine phosphorylation mediates
      the recruitment and then activation of the tyrosine phosphatase SHP-2, which in
      turn promotes the turnover of focal adhesions and the extension of filopodia,
      processes critical to cell motility. While these studies have implicated PECAM-1
      dependent signaling in PECAM-1-mediated cell motility, the involvement of PECAM-1
      ligand binding in cell migration is undefined. Therefore to investigate the role
      of PECAM-1 binding interactions in cell motility, mutants of PECAM-1 were
      generated in which either homophilic or heparin/glycosaminoglycan (GAG)-mediated
      heterophilic binding had been disabled and then expressed in an endothelial cell
      surrogate. We found that the ability of PECAM-1 to stimulate cell migration,
      promote filopodia formation and trigger Cdc42 activation were lost if PECAM-1
      dependent homophilic or heparin/GAG-dependent heterophilic ligand binding was
      disabled. We further observed that PECAM-1 concentrated at the tips of extended
      filopodia, an activity that was diminished if homophilic, but not heparin/GAG
      mediated heterophilic binding had been disrupted. Similar patterns of activities
      were seen in mouse endothelial cells treated with antibodies that specifically
      block PECAM-1-dependent homophilic or heterophilic adhesion. Together these data
      provide evidence for the differential involvement of PECAM-1-ligand interactions
      in PECAM-1-dependent motility and the extension of filopodia.

PMID- 27895232
TI  - An erudite encounter with: Guy Goodwin.

PMID- 27895230
TI  - An arginase-1 SNP that protects against the development of pulmonary hypertension
      in bronchopulmonary dysplasia enhances NO-mediated apoptosis in lymphocytes.
AB  - Arginase and nitric oxide synthase (NOS) share a common substrate, l-arginine,
      and have opposing effects on vascular remodeling. Arginase is the first step in
      polyamine and proline synthesis necessary for cellular proliferation, while NO
      produced from NOS promotes apoptosis. Previously, we identified a single
      nucleotide polymorphism (SNP) in the arginase-1 (ARG1) gene, rs2781666 (T-allele)
      that was associated with a decreased risk for developing pulmonary hypertension
      (PH) in a cohort of infants with bronchopulmonary dysplasia (BPD). In this study,
      we utilized lymphocytes from neonates (the only readily available cells from
      these patients expressing the two genotypes of interest) with either the
      rs2781666 SNP (TT) or wild type (GG) to test the hypothesis that the protection
      of the ARG1 SNP against the development of PH in BPD would involve augmented NO
      production leading to more apoptosis. Lymphocytes were stimulated with IL-4, IL
      13, and phorbol myristate acetate (PMA). We found that TT lymphocytes had similar
      levels of arginase I and arginase II expression, but there was a tendency for
      lower urea production (a surrogate marker of arginase activity), than in the GG
      lymphocytes. The TT lymphocytes also had significantly greater NO production than
      did GG lymphocytes despite no differences in iNOS expression between genotypes.
      Furthermore, the TT lymphocytes had lower numbers of viable cells, and higher
      levels of cleaved caspase-3 than did GG lymphocytes. Inhibiting NOS activity
      using Nomega-Nitro-l-arginine methyl ester hydrochloride (l-NAME) significantly
      decreased cleaved caspase-3 levels in the TT lymphocytes. These data demonstrate
      that the TT genotype results in greater levels of NO production leading to more
      apoptosis, which is consistent with the concept that BPD patients with the TT
      genotype are protected against the development of PH by producing greater basal
      levels of endogenous NO.

PMID- 27895233
TI  - Movies in Mind: Tamasha Will the 'authentic self' please stand up?

PMID- 27895234
TI  - Ultraviolet Raman Wide-Field Hyperspectral Imaging Spectrometer for Standoff
      Trace Explosive Detection.
AB  - We constructed the first deep ultraviolet (UV) Raman standoff wide-field imaging
      spectrometer. Our novel deep UV imaging spectrometer utilizes a photonic crystal
      to select Raman spectral regions for detection. The photonic crystal is composed
      of highly charged, monodisperse 35.5 +/- 2.9 nm silica nanoparticles that self
      assemble in solution to produce a face centered cubic crystalline colloidal array
      that Bragg diffracts a narrow ~1.0 nm full width at half-maximum (FWHM) UV
      spectral region. We utilize this photonic crystal to select and image two
      different spectral regions containing resonance Raman bands of pentaerythritol
      tetranitrate (PETN) and NH4NO3 (AN). These two deep UV Raman spectral regions
      diffracted were selected by angle tuning the photonic crystal. We utilized this
      imaging spectrometer to measure 229 nm excited UV Raman images containing ~10
      1000 ug/cm2 samples of solid PETN and AN on aluminum surfaces at 2.3 m standoff
      distances. We estimate detection limits of ~1 ug/cm2 for PETN and AN films under
      these experimental conditions.

PMID- 27895235
TI  - Benzodiazepine Initiation and Dose Escalation.
AB  - BACKGROUND: Benzodiazepines (BZDs) place patients at a significant risk of
      falling. The current literature does not address if this risk is increased during
      initiation or dose escalations of BZDs. OBJECTIVE: To determine if initiation or
      dose escalations of BZD regimens are associated with an increased risk of falls
      in hospitalized patients compared with patients maintained on their home dose or
      who had their dose decreased from baseline. METHODS: This retrospective case
      control study evaluated hospitalized patients aged 45 years or older who received
      a BZD. Patients who did not fall were collected in a 3:1 ratio to patients who
      fell. Comparisons were made between BZD regimens prior to admission and those 48
      hours prior to the index date. The date of fall served as the index date for
      patients who fell, and the median time-to-fall served as the index date for all
      other patients. RESULTS: A total of 132 patients were included in the study (33
      falls and 99 without a fall). No significant differences were noted in
      demographics, baseline mobility, or past medical history. Patients who fell had a
      significantly longer median length of stay (15 vs 10 days; P = 0.025).
      Additionally, patients who fell were more likely to have had their BZD regimen
      initiated or dose escalated compared with patients who did not fall (63.6% vs
      41.4%; P = 0.043). CONCLUSIONS: The risk of falling while on a BZD is increased
      on initiation and dose escalations. Hospitals should ensure judicious use of BZDs
      in inpatients to reduce the risk of falls.

PMID- 27895236
TI  - Single-Tablet Regimens for the Treatment of HIV-1 Infection.
AB  - OBJECTIVE: To review the pharmacokinetics, safety, drug-drug interactions, and
      advantages and disadvantages of currently available single-tablet regimens (STRs)
      for HIV-1 infection. DATA SOURCES: A search using PubMed was conducted (up to
      September 2016) using the following keywords: single tablet regimen AND HIV.
      Additionally, a PubMed search was conducted for each individual STR using the
      generic names of the agents. Articles were evaluated for content, and additional
      references were identified from a review of literature citations. STUDY SELECTION
      AND DATA EXTRACTION: Studies included were predominantly phase III clinical
      trials with the exception of tenofovir alafenamide because phase I and phase II
      trials were also relevant for this new antiretroviral agent. DATA SYNTHESIS: Six
      STRs are currently available for the treatment of HIV-1. Each agent has unique
      pharmacokinetic, safety, and drug-drug interaction profiles that result in
      distinct advantages and disadvantages. Three of these agents are first-line
      recommended therapies per national guidelines because of high virological
      efficacy and tolerability. CONCLUSIONS: STRs have significantly advanced HIV
      management by minimizing pill burden and improving patient compliance. It is
      important to consider the nuances of each STR in regard to renal and hepatic
      function, drug interactions, and tolerability, to ensure safe and effective use.

PMID- 27895237
TI  - Emotional Labor: Links to Depression and Work-Related Musculoskeletal Disorders
      in Call Center Workers.
AB  - Little evidence links emotional labor to either psychological or physical health.
      This study determined whether the two types of emotional labor (i.e., surface vs.
      deep acting) were significantly associated with depressive symptoms and work
      related musculoskeletal disorders in call center workers. A cross-sectional study
      was conducted with 274 workers recruited from a call center in Seoul, South
      Korea. In adjusted regression models, levels of surface, but not deep, acting
      were significantly and positively associated with depressive symptoms. Higher
      surface acting levels were significantly and positively associated with low back
      pain; higher deep acting levels were significantly and inversely associated with
      low back pain. Study findings could inform occupational health nurses as they
      delineate differentiated strategies, according to the nature of surface and deep
      acting, to promote psychological and physical health in call center workers.

PMID- 27895238
TI  - Combined Modality Intervention for ADHD With Comorbid Reading Disorders: A Proof
      of Concept Study.
AB  - To evaluate the relative efficacy of two reading programs with and without
      adjunctive stimulant medication for children with attention-deficit/hyperactivity
      disorder and comorbid reading disorder (ADHD+RD). Sixty-five children (7-11 years
      in age) were assigned randomly to one of three intensive remedial academic
      programs (phonologically or strategy-based reading instruction, or general
      academic strategy and social skills training) in combination with either
      immediate-release methylphenidate or placebo. Multiple-blind procedures were used
      for medication/placebo, given twice daily. Children received 35 hours of
      instruction in 10 weeks, taught by a trained teacher in a separate school
      classroom, in small matched groups of 2 to 3. Children's behavior and reading
      abilities were assessed before and after intervention. Stimulant medication
      produced expected beneficial effects on hyperactive/impulsive behavioral symptoms
      (reported by classroom teachers) but none on reading. Children receiving a
      reading program showed greater gains than controls on multiple standardized
      measures of reading and related skills (regardless of medication status). Small
      sample sizes precluded interpretation of possible potentiating effects of
      stimulant medication on reading skills taught in particular reading programs.
      Intensive reading instruction, regardless of treatment with stimulant medication,
      may be efficacious in improving reading problems in children with ADHD+RD and
      warrants further investigation in a large-scale study.

PMID- 27895239
TI  - Making Space for Spatial Proportions.
AB  - The three target articles presented in this special issue converged on an
      emerging theme: the importance of spatial proportional reasoning. They suggest
      that the ability to map between symbolic fractions (like 1/5) and nonsymbolic,
      spatial representations of their sizes or magnitudes may be especially important
      for building robust fractions knowledge. In this commentary, we first reflect
      upon where these findings stand in a larger theoretical context, largely borrowed
      from mathematics education research. Next, we emphasize parallels between this
      work and emerging work suggesting that nonsymbolic proportional reasoning may
      provide an intuitive foundation for understanding fraction magnitudes. Finally,
      we end by exploring some open questions that suggest specific future directions
      in this burgeoning area.

PMID- 27895240
TI  - Soaring Prescription Drug Prices.

PMID- 27895241
TI  - Secular pattern of aneurismal rupture with the lunar cycle and season.
AB  - Background The lunar cycle and seasons may be associated with rates of rupture of
      intracranial aneurysms, but the literature is mixed. Studies of the association
      between the lunar cycle and rates of aneurysm rupture used the eight qualitative
      moon phases. The purpose of this study was to assess any association of aneurysm
      rupture with the lunar cycle and with the season. Materials and methods We
      retrospectively reviewed all cases of subarachnoid haemorrhage secondary to
      ruptured intracranial aneurysm treated with endovascular coiling in our
      institution over a 10-year period. We included only cases with a known rupture
      date. We used the degree of illumination of the moon to quantitatively code the
      lunar cycle. Results A total of 212 cases were included in our analyses. The odds
      of aneurysm rupture were significantly greater ( p < 0.001) when the moon was
      least (new moon) and most (full moon) illuminated, as compared to the middle of
      the lunar cycle. The odds of rupture tended to be higher ( p = 0.059) in the
      summer, compared to autumn. Conclusions The odds of aneurysm rupture were greater
      when the moon was least illuminated (new moon) and most illuminated (full moon),
      compared to the middle of the lunar cycle.

PMID- 27895243
TI  - Contrast-less stent placement for vertebral artery origin stenosis.
AB  - We performed stent placement under intravascular ultrasound (IVUS), without the
      use of contrast medium, in a male patient in his 70s who had vertebral artery
      origin stenosis and decreased renal function. Satisfactory dilatation was
      achieved without complications, and the patient remained asymptomatic at 2 years
      of follow-up. We now report the details of this procedure. Stent placement under
      IVUS guidance may be useful in patients in whom contrast medium is
      contraindicated.

PMID- 27895242
TI  - Availability of endovascular therapies for cerebrovascular disease at primary
      stroke centers.
AB  - Background Endovascular therapies (EVTs) are useful for treating cerebrovascular
      disease. There are few data about the availability of such services at primary
      stroke centers (PSCs). Our hypothesis was that some of these services may be
      available at some PSCs. Methods We conducted an internet-based survey of
      hospitals certified as PSCs by the Joint Commission. The survey inquired about
      EVTs such as intra-arterial (IA) lytics, IA mechanical clot removal, coiling of
      aneurysms, and cervical arterial stenting, physician training, coverage models,
      hospital type, and outcomes. Chi-square analyses were used to detect differences
      between academic and community PSCs. Results Data were available from 352 PSCs,
      of which 75% were community hospitals, 23% academic medical centers, and 80% were
      non-profit; almost half (48%) see 300 or more patients annually with ischemic
      stroke. A majority (60%) provided some or all EVTs on site, while 29% had none on
      site and no plans to add them. Among the respondents offering EVTs, 95% offered
      stenting of neck vessels, 86% IA lytics, 80% IA mechanical, and 74% aneurysm
      coiling. The majority (>55%) that did offer such services provided them 24/7/365.
      Most endovascular coverage was provided by interventional neuroradiologists
      (60%), fellowship trained endovascular neurosurgeons (42%), and interventional
      radiologists (41%). The majority of hospitals (81%) did not participate in an
      audited national registry. Conclusions A variety of EVT services are offered at
      many PSCs by interventionalists with diverse types of training. The availability
      of such services is clinically relevant now with the proven efficacy of
      mechanical thrombectomy for ischemic stroke.

PMID- 27895245
TI  - Acute hippocampal and chronic diffuse white matter involvement in severe methanol
      intoxication.

PMID- 27895246
TI  - A case of congenital anosmia.

PMID- 27895247
TI  - A dual concurrent mechanism explains trigeminal neuralgia in patients with
      multiple sclerosis.

PMID- 27895248
TI  - Neurologic signs and symptoms frequently manifest in acute HIV infection.

PMID- 27895249
TI  - Mystery Case: CSF-1R mutation is a cause of intracranial cerebral calcifications,
      cysts, and leukoencephalopathy.

PMID- 27895250
TI  - Clinical Reasoning: A 70-year-old woman with acute-onset weakness and progressive
      hemiataxia.

PMID- 27895252
TI  - Teaching NeuroImages: Idiopathic hypertrophic pachymeningitis.

PMID- 27895251
TI  - Teaching NeuroImages: Orbital infarction syndrome from giant cell arteritis.

PMID- 27895253
TI  - Diagnosis of attention-deficit/hyperactivity disorder.

PMID- 27895254
TI  - Can Eosinophil Count, Platelet Count, and Mean Platelet Volume Be a Positive
      Predictive Factor in Penile Arteriogenic Erectile Dysfunction Etiopathogenesis?
AB  - Blood count parameters of patients referring with erectile dysfunction (ED) were
      examined in this study and it was investigated whether eosinophil count (EC),
      platelet count (PC), and mean platelet volume values among the suspected
      predictive parameters which may play a role in especially penile arteriogenic ED
      etiopathogenesis had a contribution on pathogenesis. Patients referring with ED
      complaint were evaluated. Depending on the medical story, ED degree was
      determined by measuring International Index of Erectile Function. Penile Doppler
      ultrasonography was taken in patients suspected to have vasculogenic ED.
      According to penile Doppler ultrasonography result, patients with arterial
      deficiency were included in the penile arteriogenic ED group and the patients
      with normal results were included in the nonvasculogenic ED group. A total of 36
      patients participated in the study from the penile arteriogenic ED group and 32
      patients from the nonvasculogenic ED group. Compared with the nonvasculogenic ED
      group, the penile arteriogenic ED group's low International Index of Erectile
      Function score, high EC, mean platelet volume and PC values were detected to be
      statistically significant ( p < .001, p = .021, p = .018, p = .034,
      respectively). No statistically significant difference was observed among the two
      groups when age, white blood cells, red blood cells, and hemoglobin values were
      considered. Pansystolic volume velocities were detected as statistically
      significantly low compared with the nonvasculogenic ED group in the measurements
      made in 5th, 10th, 15th, and 20th minutes on the right and left sides in the
      penile arteriogenic ED group. High MPV value and PC is a significant predictive
      factor for penile arteriogenic ED and vasculogenic ED and high EC is specifically
      predictive of arteriogenic ED.

PMID- 27895256
TI  - A Sr2+-metal-organic framework with high chemical stability: synthesis, crystal
      structure and photoluminescence property.
AB  - Metal-organic frameworks (MOFs) are typically built by assembly of metal centres
      and organic linkers, and have emerged as promising crystalline materials in a
      variety of fields. However, the stability of MOFs is a key limitation for their
      practical applications. Herein, we report a novel Sr 2+: -MOF
      [Sr4(Tdada)2(H2O)3(DMF)2] (denoted as NKU- 105: , NKU = Nankai University;
      H4Tdada = 5,5'-((thiophene-2,5-dicar bonyl)bis(azanediyl))diisophthalic acid; DMF
      = N,N-dimethylformamide) featuring an open square channel of about 6 A along the
      c-axis. Notably, NKU- 105: exhibits much outstanding chemical stability against
      common organic solvents, boiling water, acids and bases, relative to most MOF
      materials. Furthermore, NKU- 105: is an environment-friendly luminescent material
      with a bright cyan emission.This article is part of the themed issue
      'Coordination polymers and metal-organic frameworks: materials by design'.

PMID- 27895255
TI  - Flue-gas and direct-air capture of CO2 by porous metal-organic materials.
AB  - Sequestration of CO2, either from gas mixtures or directly from air (direct air
      capture), is a technological goal important to large-scale industrial processes
      such as gas purification and the mitigation of carbon emissions. Previously, we
      investigated five porous materials, three porous metal-organic materials (MOMs),
      a benchmark inorganic material, ZEOLITE 13X: and a chemisorbent, TEPA-SBA-15: ,
      for their ability to adsorb CO2 directly from air and from simulated flue-gas. In
      this contribution, a further 10 physisorbent materials that exhibit strong
      interactions with CO2 have been evaluated by temperature-programmed desorption
      for their potential utility in carbon capture applications: four hybrid
      ultramicroporous materials, SIFSIX-3-CU: , DICRO-3-NI-I: , SIFSIX-2-CU-I: and
      MOOFOUR-1-NI: ; five microporous MOMs, DMOF-1: , ZIF-8: , MIL-101: , UIO-66: and
      UIO-66-NH2: ; an ultramicroporous MOM, NI-4-PYC: The performance of these MOMs
      was found to be negatively impacted by moisture. Overall, we demonstrate that the
      incorporation of strong electrostatics from inorganic moieties combined with
      ultramicropores offers improved CO2 capture performance from even moist gas
      mixtures but not enough to compete with chemisorbents.This article is part of the
      themed issue 'Coordination polymers and metal-organic frameworks: materials by
      design'.

PMID- 27895257
TI  - The modulator driven polymorphism of Zr(IV) based metal-organic frameworks.
AB  - The reaction of ZrCl4 and 2,5-thiophenedicarboxylic acid (H2tdc) in the presence
      of trifluoroacetic acid (Htfa) as modulator results in the formation of the new
      metal-organic framework (MOF) named DUT-126 (DUT = Dresden University of
      Technology). The nature and concentration of modulators are found to be decisive
      synthetic parameters affecting the topology of the formed product. DUT-126 ( HBR:
      ) extends the series of polymorphs differing in topology, namely DUT-67 ( REO: ),
      DUT-68 ( BON: ) and DUT-69 ( BCT: ) to four, where DUT-67 and DUT-68 show the
      same eight-connected secondary building units as in DUT-126. In DUT-126, linker
      molecules have a peculiar orientation, resulting in HBR: topology, which is
      described for the first time in this work for MOFs. DUT-126 contains three pore
      types, including two micropores surrounding mesoporous channels. DUT-126 is
      stable against hydrolysis and features permanent porosity with a specific surface
      area of 1297 m2 g-1 and a total pore volume of 0.48 cm3 g-1, calculated from the
      nitrogen physisorption isotherm measured at 77 K.This article is part of the
      themed issue 'Coordination polymers and metal-organic frameworks: materials by
      design'.

PMID- 27895258
TI  - X-ray crystallographic insights into post-synthetic metalation products in a
      metal-organic framework.
AB  - Post-synthetic modification of metal-organic frameworks (MOFs) facilitates a
      strategic transformation of potentially inert frameworks into functionalized
      materials, tailoring them for specific applications. In particular, the post
      synthetic incorporation of transition-metal complexes within MOFs, a process
      known as 'metalation', is a particularly promising avenue towards functionalizing
      MOFs. Herein, we describe the post-synthetic metalation of a microporous MOF with
      various transition-metal nitrates. The parent framework, 1: , contains free
      nitrogen donor chelation sites, which readily coordinate metal complexes in a
      single-crystal to single-crystal transformation which, remarkably, can be readily
      monitored by X-ray crystallography. The presence of an open void surrounding the
      chelation site in 1: prompted us to investigate the effect of the MOF pore
      environment on included metal complexes, particularly examining whether void
      space would induce changes in the coordination sphere of chelated complexes
      reminiscent of those found in the solution state. To test this hypothesis, we
      systematically metalated 1: with first-row transition-metal nitrates and
      elucidated the coordination environment of the respective transition-metal
      complexes using X-ray crystallography. Comparison of the coordination sphere
      parameters of coordinated transition-metal complexes in 1: against equivalent
      solid- and solution-state species suggests that the void space in 1: does not
      markedly influence the coordination sphere of chelated species but we show
      notably different post-synthetic metalation outcomes when different solvents are
      used.This article is part of the themed issue 'Coordination polymers and metal
      organic frameworks: materials by design'.

PMID- 27895259
TI  - Arene guest selectivity and pore flexibility in a metal-organic framework with
      semi-fluorinated channel walls.
AB  - A metal-organic framework (MOF) with one-dimensional channels of approximately
      hexagonal cross-section [Ag2(O2CCF2CF2CO2)(TMP)] 1: (TMP =2,3,5,6
      tetramethylpyrazine) has been synthesized with MeOH filling the channels in its
      as-synthesized form as [Ag2(O2CCF2CF2CO2)(TMP)].n(MeOH) 1-MEOH: (n = 1.625 by X
      ray crystallography). The two types of ligand connect columns of Ag(I) centres in
      an alternating manner, both around the channels and along their length, leading
      to an alternating arrangement of hydrocarbon (C-H) and fluorocarbon (C-F) groups
      lining the channel walls, with the former groups projecting further into the
      channel than the latter. MeOH solvent in the channels can be exchanged for a
      variety of arene guests, ranging from xylenes to tetrafluorobenzene, as confirmed
      by gas chromatography, 1H nuclear magnetic resonance (NMR) spectroscopy,
      thermogravimetric analysis and 13C cross-polarization magic angle spinning NMR
      spectroscopy. Alkane and perfluoroalkane guests, however, do not enter the
      channels. Although exhibiting some stability under a nitrogen atmosphere,
      sufficient to enable crystal structure determination, the evacuated MOF 1: is
      unstable for periods of more than minutes under ambient conditions or upon
      heating, whereupon it undergoes an irreversible solid-state transformation to a
      non-porous polymorph 2: , which comprises Ag2(O2CCF2CF2CO2) coordination layers
      that are pillared by TMP ligands. This transformation has been followed in situ
      by powder X-ray diffraction and shown to proceed via a crystalline
      intermediate.This article is part of the themed issue 'Coordination polymers and
      metal-organic frameworks: materials by design'.

PMID- 27895260
TI  - Coordination polymers and metal-organic frameworks: materials by design.

PMID- 27895261
TI  - Photochemistry of framework-supported M(diimine)(CO)3X complexes in three
      dimensional lithium carboxylate metal-organic frameworks: monitoring the effect
      of framework cations.
AB  - The structures and photochemical behaviour of two new metal-organic frameworks
      (MOFs) are reported. Reaction of Re(2,2'-bipy-5,5'-dicarboxylic acid)(CO)3Cl or
      Mn(2,2'-bipy-5,5'-dicarboxylic acid)(CO)3Br with LiCl or LiBr, respectively,
      produces single crystals of {Li2(DMF)2 [(2,2'-bipy-5,5'
      dicarboxylate)Re(CO)3Cl]}n ( RELI: ) or {Li2(DMF)2[(2,2'-bipy-5,5'
      dicarboxylate)Mn(CO)3Br]}n ( MNLI: ). The structures formed by the two MOFs
      comprise one-dimensional chains of carboxylate-bridged Li(I) cations that are
      cross-linked by units of Re(2,2'-bipy-5,5'-dicarboxylate)(CO)3Cl ( RELI: ) or
      Mn(2,2'-bipy-5,5'- dicarboxylate)(CO)3Br ( MNLI: ). The photophysical and
      photochemical behaviour of both RELI: and MNLI: are probed. The rhenium
      containing MOF, RELI: , exhibits luminescence and the excited state behaviour, as
      established by time-resolved infrared measurements, is closer in behaviour to
      that of unsubstituted [Re(bipy)(CO)3Cl] rather than a related MOF where the Li(I)
      cations are replaced by Mn(II) cations. These observations are further supported
      by density functional theory calculations. Upon excitation MNLI: forms a
      dicarbonyl species which rapidly recombines with the dissociated CO, in a fashion
      consistent with the majority of the photoejected CO not escaping the MOF
      channels.This article is part of the themed issue 'Coordination polymers and
      metal-organic frameworks: materials by design'.

PMID- 27895262
TI  - Gas adsorption and structural diversity in a family of Cu(II) pyridyl
      isophthalate metal-organic framework materials.
AB  - A family of Cu(II)-based metal-organic frameworks (MOFs) has been synthesized
      using three pyridyl-isophthalate ligands, H2L1 (4'-(pyridin-4-yl)biphenyl-3,5
      dicarboxylic acid), H2L2 (4''-(pyridin-4-yl)-1,1':4',1''-terphenyl-3,5
      dicarboxylic acid) and H2L3 (5-[4-(pyridin-4-yl)naphthalen-1-yl]benzene-1,3
      dicarboxylic acid). Although in each case the pyridyl-isophthalate ligands adopt
      the same pseudo-octahedral [Cu2(O2CR)4N2] paddlewheel coordination modes, the
      resulting frameworks are structurally diverse, particularly in the case of the
      complex of Cu(II) with H2L3, which leads to three distinct supramolecular
      isomers, each derived from Kagome and square nets. In contrast to [Cu(L2)] and
      the isomers of [Cu(L3)], [Cu(L1)] exhibits permanent porosity. Thus, the gas
      adsorption properties of [Cu(L1)] were investigated with N2, CO2 and H2, and the
      material exhibits an isosteric heat of adsorption competitive with leading MOF
      sorbents for CO2 [Cu(L1)] displays high H2 adsorption, with the density in the
      pores approaching that of liquid H2This article is part of the themed issue
      'Coordination polymers and metal-organic frameworks: materials by design'.

PMID- 27895263
TI  - Editorial.

PMID- 27895265
TI  - Gut Homeostasis, Microbial Dysbiosis, and Opioids.
AB  - Gut homeostasis plays an important role in maintaining animal and human health.
      The disruption of gut homeostasis has been shown to be associated with multiple
      diseases. The mutually beneficial relationship between the gut microbiota and the
      host has been demonstrated to maintain homeostasis of the mucosal immunity and
      preserve the integrity of the gut epithelial barrier. Currently, rapid progress
      in the understanding of the host-microbial interaction has redefined
      toxicological pathology of opioids and their pharmacokinetics. However, it is
      unclear how opioids modulate the gut microbiome and metabolome. Our study,
      showing opioid modulation of gut homeostasis in mice, suggests that medical
      interventions to ameliorate the consequences of drug use/abuse will provide
      potential therapeutic and diagnostic strategies for opioid-modulated intestinal
      infections. The study of morphine's modulation of the gut microbiome and
      metabolome will shed light on the toxicological pathology of opioids and its role
      in the susceptibility to infectious diseases.

PMID- 27895266
TI  - A simple method to estimate the time-dependent receiver operating characteristic
      curve and the area under the curve with right censored data.
AB  - The time-dependent receiver operating characteristic curve is often used to study
      the diagnostic accuracy of a single continuous biomarker, measured at baseline,
      on the onset of a disease condition when the disease onset may occur at different
      times during the follow-up and hence may be right censored. Due to right
      censoring, the true disease onset status prior to the pre-specified time horizon
      may be unknown for some patients, which causes difficulty in calculating the time
      dependent sensitivity and specificity. We propose to estimate the time-dependent
      sensitivity and specificity by weighting the censored data by the conditional
      probability of disease onset prior to the time horizon given the biomarker, the
      observed time to event, and the censoring indicator, with the weights calculated
      nonparametrically through a kernel regression on time to event. With this
      nonparametric weighting adjustment, we derive a novel, closed-form formula to
      calculate the area under the time-dependent receiver operating characteristic
      curve. We demonstrate through numerical study and theoretical arguments that the
      proposed method is insensitive to misspecification of the kernel bandwidth,
      produces unbiased and efficient estimators of time-dependent sensitivity and
      specificity, the area under the curve, and other estimands from the receiver
      operating characteristic curve, and outperforms several other published methods
      currently implemented in R packages.

PMID- 27895267
TI  - Prototype Positive Control Wells for Malaria Rapid Diagnostic Tests: Prospective
      Evaluation of Implementation Among Health Workers in Lao People's Democratic
      Republic and Uganda.
AB  - Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis, but lack of
      quality control at point of care restricts trust in test results. Prototype
      positive control wells (PCW) containing recombinant malaria antigens have been
      developed to identify poor-quality RDT lots. This study assessed community and
      facility health workers' (HW) ability to use PCWs to detect degraded RDTs, the
      impact of PCW availability on RDT use and prescribing, and preferred strategies
      for implementation in Lao People's Democratic Republic (Laos) and Uganda. A total
      of 557 HWs participated in Laos (267) and Uganda (290). After training, most (88%
      to >= 99%) participants correctly performed the six key individual PCW steps;
      performance was generally maintained during the 6-month study period. Nearly all
      (97%) reported a correct action based on PCW use at routine work sites. In
      Uganda, where data for 127,775 individual patients were available, PCW
      introduction in health facilities was followed by a decrease in antimalarial
      prescribing for RDT-negative patients >= 5 years of age (4.7-1.9%); among
      community-based HWs, the decrease was 12.2% (P < 0.05) for all patients.
      Qualitative data revealed PCWs as a way to confirm RDT quality and restore
      confidence in RDT results. HWs in malaria-endemic areas are able to use prototype
      PCWs for quality control of malaria RDTs. PCW availability can improve HWs'
      confidence in RDT results, and benefit malaria diagnostic programs. Lessons
      learned from this study may be valuable for introduction of other point-of-care
      diagnostic and quality-control tools. Future work should evaluate longer term
      impacts of PCWs on patient management.

PMID- 27895268
TI  - Credit with Health Education in Benin: A Cluster Randomized Trial Examining
      Impacts on Knowledge and Behavior.
AB  - We evaluate whether health education integrated into microcredit lending groups
      reduces health risks by improving health knowledge and self-reported behaviors
      among urban and rural borrowers in eastern Benin. In 2007, we randomly assigned
      138 villages in the Plateau region of Benin to one of four variations of a group
      liability credit product, varying lending groups' gender composition and/or
      inclusion of health education using a 2 * 2 design. Women in villages receiving
      health education, regardless of gender composition of the groups, showed improved
      knowledge of malaria and of human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS), but not of childhood illness danger signs.
      No significant changes in health behavior were observed except an increase in
      HIV/AIDS prevention behavior, a result predominantly driven by an increase in
      respondents' self-reported ability to procure a condom, likely an indicator of
      increased perceived access rather than improved preventative behavior. Women in
      villages assigned to mixed-gender groups had significantly lower levels of social
      capital, compared with villages assigned to female-only groups. This suggests
      there may be an important trade-off to consider for interventions seeking
      improved health outcomes and social capital through provision of services to
      mixed-gender groups. Although bundling health education with microcredit can
      expand health education coverage and lower service-delivery costs, the approach
      may not be sufficient to improve health behaviors.

PMID- 27895264
TI  - Sex Differences in Human and Animal Toxicology.
AB  - Sex, the states of being female or male, potentially interacts with all
      xenobiotic exposures, both inadvertent and deliberate, and influences their
      toxicokinetics (TK), toxicodynamics, and outcomes. Sex differences occur in
      behavior, exposure, anatomy, physiology, biochemistry, and genetics, accounting
      for female-male differences in responses to environmental chemicals, diet, and
      pharmaceuticals, including adverse drug reactions (ADRs). Often viewed as an
      annoying confounder, researchers have studied only one sex, adjusted for sex, or
      ignored it. Occupational epidemiology, the basis for understanding many toxic
      effects in humans, usually excluded women. Likewise, Food and Drug Administration
      rules excluded women of childbearing age from drug studies for many years. Aside
      from sex-specific organs, sex differences and sex * age interactions occur for a
      wide range of disease states as well as hormone-influenced conditions and drug
      distribution. Women have more ADRs than men; the classic sex hormone paradigm
      (gonadectomy and replacement) reveals significant interaction of sex and TK
      including absorption, distribution, metabolisms, and elimination. Studies should
      be designed to detect sex differences, describe the mechanisms, and interpret
      these in a broad social, clinical, and evolutionary context with phenomena that
      do not differ. Sex matters, but how much of a difference is needed to matter
      remains challenging.

PMID- 27895269
TI  - Stability of Dihydroartemisinin-Piperaquine Tablet Halves During Prolonged
      Storage Under Tropical Conditions.
AB  - Dihydroartemisinin-piperaquine (DP) is recommended for the treatment of
      uncomplicated malaria, used in efforts to contain artemisinin resistance, and
      increasingly considered for mass drug administration. Because of the narrow
      therapeutic dose range and available tablet strengths, the manufacturers and
      World Health Organization recommended regimens involve breaking tablets into
      halves to accurately dose children according to body weight. Use of tablet
      fractions in programmatic settings under tropical conditions requires a highly
      stable product; however, the stability of DP tablet fractions is unknown. We aged
      full and half DP (Eurartesim(r)) tablets in a stability chamber at 30 degrees C
      and 70% humidity level. The active pharmaceutical ingredients dihydroartemisinin
      and piperaquine remained at >= 95% over the 3 months' period of ageing in light
      and darkness. These findings are reassuring for DP, but highlight the need to
      assess drug stability under real-life settings during the drug development
      process, particularly for key drugs of global disease control programs.

PMID- 27895270
TI  - Dicrocoelium dendriticum: An Unusual Parasitological Diagnosis in a Reference
      International Health Unit.
AB  - Finding Dicrocoelium dendriticum eggs in human feces is exceptional and there are
      few prevalence data available. True infection occurs after accidental ingestion
      of ants containing metacercariae and spurious infection through the consumption
      of infected animal liver. Differential diagnosis between true and pseudo
      infections is performed through stool examination after a diet free of liver. In
      addition, microscopy can help to differentiate the type of infection. We report
      six cases, all from sub-Saharan Africa, detection of this fluke at the Tropical
      Medicine Unit Vall d'Hebron-Drassanes (Barcelona, Spain). Dicrocoelium
      dendriticum transit eggs were visualized in five cases and there were no
      subsequent visualizations after diet, which reinforces that all these cases were
      false parasitism. In one case, few embryonated eggs were observed and the patient
      was treated for a possible true parasitism. There is a need to investigate the
      prevalence of D. dendriticum in our country focusing on the distinction between
      true and spurious infections.

PMID- 27895272
TI  - Dengue Infection in a Human Immunodeficiency Virus-1 Positive Patient Chronically
      Infected with Hepatitis B Virus in Western Mexico.
AB  - Human immunodeficiency virus (HIV) and dengue coinfection has not been
      extensively studied. We report herein a case of dengue serotype 1 infection in an
      HIV-1-positive patient coinfected with hepatitis B virus (HBV) in Colima State,
      Mexico. CD4+ cells and HIV-1 viremia remained at normal levels, and no severe
      complications were observed during this multiple viral infection. The alanine
      transaminase and aspartate transaminase values were elevated before and during
      dengue infection. Surprisingly, these parameters were significantly reduced 2
      months later. Because of the lack of evidence regarding this multiple viral
      interaction, further research is required to understand the biologic and clinical
      course of dengue infection in HIV-1/HBV coinfected patients, especially in
      tropical regions where dengue virus transmission is highly active.

PMID- 27895273
TI  - Results from the Workshop "Problem Formulation for the Use of Gene Drive in
      Mosquitoes".
AB  - Reducing the incidence of malaria has been a public health priority for nearly a
      century. New technologies and associated vector control strategies play an
      important role in the prospect of sustained reductions. The development of the
      CRISPR/Cas9 gene editing system has generated new possibilities for the use of
      gene-drive constructs to reduce or alter vector populations to reduce malaria
      incidence. However, before these technologies can be developed and exploited, it
      will be necessary to understand and assess the likelihood of any potential harms
      to humans or the environment. To begin this process, the Foundation for the
      National Institutes of Health and the International Life Sciences Institute
      Research Foundation organized an expert workshop to consider the potential risks
      related to the use of gene drives in Anopheles gambiae for malaria control in
      Africa. The resulting discussion yielded a series of consensus points that are
      reported here.

PMID- 27895271
TI  - Examination of Antibody Responses as a Measure of Exposure to Malaria in the
      Indigenous Batwa and Their Non-Indigenous Neighbors in Southwestern Uganda.
AB  - Understanding variations in malaria transmission and exposure is critical to
      identify populations at risk and enable better targeting of interventions. The
      indigenous Batwa of southwestern Uganda have a disproportionate burden of malaria
      infection compared with their non-indigenous neighbors. To better understand the
      individual- and community-level determinants of malaria exposure, a
      seroepidemiological study was conducted in 10 local council cells in Kanungu
      District, Uganda, in April 2014. The Batwa had twice the odds of being
      seropositive to two Plasmodium falciparum-specific antigens, apical membrane
      antigen-1 and merozoite surface protein-119, compared with the non-indigenous
      Bakiga (odds ratio = 2.08, 95% confidence interval = 1.51-2.88). This trend was
      found irrespective of altitude level and after controlling for cell location.
      Seroconversion rates in the Batwa were more than twice those observed in the
      Bakiga. For the Batwa, multiple factors may be associated with higher exposure to
      malaria and antibody levels relative to their non-indigenous neighbors.

PMID- 27895274
TI  - Disease Severity Prediction by Spirometry in Adults with Visceral Leishmaniasis
      from Minas Gerais, Brazil.
AB  - Visceral leishmaniasis (VL) is associated with interstitial pneumonitis according
      to histology and radiology reports. However, studies to address the functional
      impact on respiratory function in patients are lacking. We assessed pulmonary
      function using noninvasive spirometry in a cross-sectional study of hospitalized
      adult VL patients from Minas Gerais, Brazil, without unrelated lung conditions or
      acute infections. Lung conditions were graded as normal, restrictive,
      obstructive, or mixed patterns, according to Brazilian consensus standards for
      spirometry. To control for regional patterns of lung function, we compared
      spirometry of patients with regional paired controls. Spirometry detected
      abnormal lung function in most VL patients (70%, 14/20), usually showing a
      restrictive pattern, in contrast to regional controls and the standards for
      normal tests. Alterations in spirometry measurements correlated with
      hypoalbuminemia, the only laboratory value indicative of severity of parasitic
      disease. Abnormalities did not correlate with unrelated factors such as smoking
      or occupation. Clinical data including pulmonary symptoms and duration of therapy
      were also unrelated to abnormal spirometry findings. We conclude that the
      severity of VL is correlated with a restrictive pattern of lung function
      according to spirometry, suggesting that there may be interstitial lung
      involvement in VL. Further studies should address whether spirometry could serve
      as an index of disease severity in the management of VL.

PMID- 27895275
TI  - Sequence-Independent, Single-Primer Amplification Next-Generation Sequencing of
      Hantaan Virus Cell Culture-Based Isolates.
AB  - Hantaan virus (HTNV), identified in the striped field mouse (Apodemus agrarius),
      belongs to the genus Hantavirus of the family Bunyaviridae and contains
      tripartite RNA genomes, small (S), medium (M), and large (L) segments. HTNV is a
      major causative for hemorrhagic fever with renal syndrome (HFRS) with fatality
      rates ranging from 1% to 15% in the Republic of Korea (ROK) and China. Defining
      of HTNV whole-genome sequences and isolation of the infectious particle play a
      critical role in the characterization and preventive and therapeutic strategies
      of hantavirus outbreaks. Next-generation sequencing (NGS) provides an advanced
      tool for massive genomic sequencing of viruses. However, the isolation of viral
      infectious particles is a huge obstacle to investigate and develop anti-virals
      for hantaviruses. Here, we report 12 HTNV isolates from lung tissues of the
      striped field mouse in the highly HFRS-endemic areas. Sequence-independent,
      single-primer amplification (SISPA) NGS was attempted to recover the genomic
      sequences of HTNV isolates. The nucleotide sequence of HTNV S, M, and L segments
      were covered up to 99.4-100%, 97.5-100%, and 95.6-99.8%, respectively, based on
      the full length of the prototype HTNV 76-118. The whole-genome sequencing of HTNV
      isolates was accomplished by additional reverse transcription polymerase chain
      reaction (RT-PCR) and rapid amplification cDNA ends (RACE) PCR. In conclusion,
      this study will lead to the attempt and usage of SISPA NGS technologies to
      delineate the whole-genome sequence of hantaviruses, providing a new era of viral
      genomics for the surveillance, trace, and disease risk management of HFRS
      incidents.

PMID- 27895276
TI  - Rubella Immunity in Pregnant Native Taiwanese and Immigrants from Asian
      Countries.
AB  - Vaccination is considered the most effective method to prevent rubella spread and
      congenital rubella syndrome (CRS). The aim of the present study was to
      investigate the rubella immunity among native and immigrant pregnant women in
      Taiwan. From 2000 to 2014, a total of 16,879 pregnant women who received routine
      prenatal examinations were recruited in this study. The rubella IgG antibodies
      were assayed using a microparticle enzyme immunoassay or chemiluminescent
      microparticle immunoassay. Subjects were categorized by nationality and
      subcategorized by specific periods of time for comparison. The rubella
      susceptibility was 12.7% in total, 11.1% in Taiwanese and 20.3% in immigrant
      population from 2000 to 2014. Among the immigrant women, those from Vietnam had
      the highest susceptibility (22.3%) and those from Thailand had the lowest
      susceptibility (3.8%). The immigrant women from Vietnam and China showed a
      significantly higher susceptibility compared with the native Taiwanese women in
      which the odds ratio was 2.30 (95% confidence interval [CI]: 2.04-2.60), 1.96
      (95% CI: 1.59-2.41), respectively (P < 0.001). It meant that immigrants from
      Vietnam and China had a higher likelihood of rubella susceptibility and related
      CRS sequela than native women. From 2000-2004 to 2010-2014 cohort, there was no
      obvious change in rubella susceptibility in native women, which varied between
      10.0% and 11.9%. However, there was a decreasing trend of rubella susceptibility
      in the immigrant women overall, from 24.5% to 11.5% (P < 0.001). To eliminate
      congenital rubella in Taiwan, additional catch-up immunization strategies are
      needed.

PMID- 27895277
TI  - Triatoma infestans Calreticulin: Gene Cloning and Expression of a Main Domain
      That Interacts with the Host Complement System.
AB  - Triatoma infestans is an important hematophagous vector of Chagas disease, a
      neglected chronic illness affecting approximately 6 million people in Latin
      America. Hematophagous insects possess several molecules in their saliva that
      counteract host defensive responses. Calreticulin (CRT), a multifunctional
      protein secreted in saliva, contributes to the feeding process in some insects.
      Human CRT (HuCRT) and Trypanosoma cruzi CRT (TcCRT) inhibit the classical pathway
      of complement activation, mainly by interacting through their central S domain
      with complement component C1. In previous studies, we have detected CRT in
      salivary gland extracts from T. infestans We have called this molecule TiCRT.
      Given that the S domain is responsible for C1 binding, we have tested its role in
      the classical pathway of complement activation in vertebrate blood. We have
      cloned and characterized the complete nucleotide sequence of CRT from T.
      infestans, and expressed its S domain. As expected, this S domain binds to human
      C1 and, as a consequence, it inhibits the classical pathway of complement, at its
      earliest stage of activation, namely the generation of C4b. Possibly, the
      presence of TiCRT in the salivary gland represents an evolutionary adaptation in
      hematophagous insects to control a potential activation of complement proteins,
      present in the massive blood meal that they ingest, with deleterious consequences
      at least on the anterior digestive tract of these insects.

PMID- 27895278
TI  - Paracoccidioidomycosis in Brazilian Patients With and Without Human
      Immunodeficiency Virus Infection.
AB  - Paracoccidioidomycosis (PCM) is endemic to Latin America, where 10 million people
      may be infected with Paracoccidioides brasiliensis/Paracoccidioides lutzii and
      1,600,000 individuals live with human immunodeficiency virus (HIV) infection. An
      epidemiological overlapping of these infections occurred early in acquired
      immunodeficiency syndrome era with nearly 180 published cases. This study
      presents epidemiological, clinical, and outcome profiles for 31 PCM patients with
      HIV infection diagnosed in a teaching hospital in Brazil, and includes an update
      of previously reported cases. Medical records were reviewed and data compared
      with 64 PCM patients without HIV infection. Of the 31 PCM patients with HIV
      infection, 23 (74.1%) were male, with a median age of 36.7 years, whereas of the
      64 PCM, 45 (70.3%) were male, with a median age of 35.1 years. Both groups
      presented similar proportions for smoking and alcoholism. PCM patients with HIV
      infection presented more fever, weight loss, and the acute clinical form than the
      PCM patients who had more mucosal and respiratory involvement characterizing the
      chronic form. Most PCM patients with HIV infection exhibited overlapping symptoms
      from both clinical forms with median symptom duration of 4.5 months compared with
      8.3 months for the PCM control. Patients received sulfonamides and/or
      itraconazole for a median of 15.7 and 16.7 months for PCM/HIV-infected and PCM,
      respectively. Relapses occurred more in PCM (12 [30%]) than PCM/HIV-infected (4
      [14.8%]) patients, whose mortality rate was higher (10 [32.8%]) than PCM patients
      (8 [20%]). The cases of PCM/HIV infection confirm that HIV can interact with some
      endemic diseases without increasing their frequency, while changing their natural
      history, clinical presentation, and outcome. The data presented here are in
      agreement with those observed in other studies.

PMID- 27895281
TI  - Transition to circular economy requires reliable statistical quantification and
      control of uncertainty and variability in waste.

PMID- 27895279
TI  - Evaluation of Immunoglobulin G Responses to Plasmodium falciparum and Plasmodium
      vivax in Malian School Children Using Multiplex Bead Assay.
AB  - Malaria serology through assaying for IgG against Plasmodium spp. antigens
      provides evidence into the infection history for an individual. The multiplex
      bead assay (MBA) allows for detection of IgG against multiple Plasmodium spp.,
      and can be especially useful in many regions where Plasmodium falciparum is of
      primary clinical focus, but other species are co-endemic. Dried blood spots were
      collected from 805 Malian children attending 42 elementary schools in the regions
      of Mopti, Sikasso, Koulikoro, and Bamako capital district, and IgG assayed by
      MBA. As southern Mali is known to be holoendemic for P. falciparum, merozoite
      surface protein 1 19-kDa subunit (MSP-142) and apical membrane antigen 1 (AMA-1)
      antigens were included for serology against this parasite. Responses to these
      antigens both provided high estimates for lifetime exposure, with 730 (90%)
      children with IgG antibodies for MSP-142, 737 (91%) for AMA-1, and 773 (96%)
      positive for either or both. Also included was the antigen Plasmodium vivax MSP
      119, against which 140 (17.4%) children were found to have antibodies. Increases
      in antibody titers with older age were clearly seen with the P. falciparum
      antigens, but not with the P. vivax antigen, likely indicating more of a
      sporadic, rather than sustained transmission for this species. The MBA provides
      effective opportunities to evaluate malaria transmission through serological
      analysis for multiple Plasmodium species.

PMID- 27895282
TI  - Liberalization in the Danish waste sector: an institutional perspective.
AB  - The push for creating a more competitive and liberalized system for traditional
      public services, including waste management, has been on the European agenda
      since the late 1980s. In 2008, changes were made in EU waste legislation allowing
      source-separated industrial/commercial waste that is suitable for incineration to
      be traded within the European market. This change has had broad implications for
      the Danish waste sector, which is characterized by institutionalized municipal
      control with all streams of waste and municipal ownership of the major treatment
      facilities allowing the municipal sector to integrate combustible waste in local
      heat and power generation. This article, applying an institutional approach, maps
      the institutions and actors of the Danish waste sector and analyses how the
      regulatory as well as normative pressure to liberalize has been met and partly
      neutralized in the institutional and political context. The new Danish regulation
      of 2010 has thus accommodated the specific requirement for liberalization, but in
      fact only represents a very small step towards a market-based waste management
      system. On the one hand, by only liberalizing industrial/commercial waste, the
      Danish Government chose to retain the main features of the established waste
      system favouring municipal control and hence the institutionalized principles of
      decentralized enforcement of environmental legislation as well as welfare state
      considerations. On the other hand, this has led to a technological and financial
      deadlock, particularly when it comes to reaching the recycling targets of EU,
      which calls for further adjustments of the Danish waste sector.

PMID- 27895283
TI  - Food waste prevention in Athens, Greece: The effect of family characteristics.
AB  - Food waste is a stream that becomes increasingly important in terms of its
      prevention potential. There is a large number of behaviours that can be
      associated with food waste generation and the efforts towards food waste
      prevention. A questionnaire study was carried in order to study consumer
      behaviour related to food provision and wastage in Greece. Proper practices of
      the respondents that can prevent the generation of food waste were investigated
      using nine behavioural scales, which were defined on the basis of similar studies
      in other countries. A structured questionnaire was utilised in order to test
      those behaviours against the socio-demographic characteristics of respondents.
      The results of the study indicate that in terms of inferential statistical
      analysis, among the numerous variables examined, those that enhance food waste
      prevention are the involvement of the respondent in cooking, the annoyance
      towards food waste generation and the education level.

PMID- 27895280
TI  - Effectiveness of Albendazole for Hookworm Varies Widely by Community and
      Correlates with Nutritional Factors: A Cross-Sectional Study of School-Age
      Children in Ghana.
AB  - Mass drug administration (MDA) targeting school-age children is recommended by
      the World Health Organization for the global control of soil-transmitted helminth
      (STH) infections. Although considered safe and cost-effective to deliver,
      benzimidazole anthelminthics are variably effective against the three most common
      STHs, and widespread use has raised concern about the potential for emerging
      resistance. To identify factors mediating response to albendazole, we conducted a
      cross-sectional study of hookworm infection in the Kintampo North Municipality of
      Ghana in 2011. Among 140 school-age children residing in five contiguous
      communities, the hookworm prevalence was 59% (82/140). The overall cure rate
      following administration of single-dose albendazole (400 mg) was 35% (27/76),
      with a community-wide fecal egg reduction rate (ERR) of 61% (95% confidence
      interval: 51.8-71.1). Significant disparities were observed in albendazole
      effectiveness by community, with a cure rate as low as 0% (N = 24) in Jato Akuraa
      and ERRs ranging from 53% to 95% across the five study sites. Individual host
      factors associated with response to deworming treatment included time since last
      meal, pretreatment blood hemoglobin level, and mid-upper arm circumference. These
      data demonstrate significant community-level variation in the effectiveness of
      albendazole, even among populations living in close proximity. Identification of
      host factors that influence response to albendazole, most notably the timing of
      drug administration and nutritional factors, creates an opportunity to enhance
      the effectiveness of deworming through targeted interventions. These findings
      also demonstrate the importance of measuring anthelminthic response as part of
      the monitoring and evaluation of community-based deworming programs.

PMID- 27895284
TI  - Spatial and temporal dynamics of agricultural residue resources in the last 30
      years in China.
AB  - The availability and distribution of biomass resources are important for the
      development of the bioenergy industry in a region. Biomass resources are abundant
      in China; however, the raw material is severely deficient, which makes the
      Chinese bioenergy industry an embarrassment and a contradiction. Unclear reserves
      and distribution and changing trends of biomass resources are the reason for this
      situation. A collection coefficient model of Chinese agricultural residue
      resources was established and the spatial and temporal pattern dynamics of
      agricultural residue resources in the last 30 years were analyzed. The results
      show that agricultural residue resources increased in stages from 1978 to 2011,
      including a rapid increase from 1978 to 1999, a significant fall from 2000 to
      2004, and a slow increase from 2004 to 2011. Crops straw and livestock manure are
      the main ingredients of agricultural residue resources with proportions of 53-59%
      and 31-38%, respectively. However, the former has gradually decreased, while the
      latter is increasing. This mainly resulted from the strategic reorganization of
      the Chinese agriculture structure and the rapid development of large-scale
      livestock breeding and agricultural mechanization. Large regional differences
      existed in Chinese agricultural residue resources, and three distribution types
      formed, including resource-rich areas in North China, Northeast and Inner
      Mongolia, resource-limited areas in Central and Southwest China, and resource
      poor areas along Northwest and Southeast coasts. This pattern is a reverse of the
      distributions of climatic conditions, water resources, economic development,
      human resources, and technological levels. Finally, it can be predicted that
      livestock manure and biomass conversion technology at low temperature will play
      increasingly significant roles in bioenergy industry development.

PMID- 27895285
TI  - Application of stability indicators for the assessment of the degradation of
      residual household waste before landfilling.
AB  - In France, domestic waste production is estimated at c 350 kg year-1 per person
      and landfilling still represents a predominant way of municipal solid waste
      management, with 39% of waste dumped in 2007. Waste characterization campaigns
      were conducted at different stages of a mechanical-biological treatment process
      in order to evaluate its efficiency. Waste samples were sorted by size (>100 mm,
      <100-20 mm and <20 mm) in order to assess the opportunity for mechanical and
      aerobic degradation and to reduce the volume of waste landfilled. The monitoring
      of parameter characteristics of waste stabilization highlighted a decrease in
      both organic matter and oxidizable organic matter, and an increase in fine
      particles <20 mm. The respirometric index after 4 days performed on waste samples
      from the pre-treatment stage showed a decrease in the biological activity
      compared with the samples taken upstream in the process. The biochemical methane
      potential of the waste is above the German limit of acceptance in landfills. This
      intermediate phase of stabilization is confirmed by the results of the leaching
      tests and hydrophobic fractionation.

PMID- 27895286
TI  - Pyrolysis of poppy capsule pulp for bio-oil production.
AB  - The feasibility of biofuel production via the pyrolysis of poppy capsule pulp,
      the main waste product of Afyon Alkoloid Factory, was investigated. The poppy
      capsule pulp was shown to have a high volatile matter content (ca. 76%).
      Pyrolysis experiments were carried out in the temperature range 400-550 degrees C
      (heating rate 18 degrees C min-1 and holding time 20 min) under a nitrogen
      atmosphere. The chemical components of the bio-oil were characterized by Fourier
      transform infrared spectrometry and gas chromatography-mass spectrometry. The
      effects of pyrolysis temperature on the production efficiency and the calorific
      value of the bio-oil were investigated. The maximum bio-oil yield and its
      calorific value at 500 degrees C were 23.6% and 31.6 MJ kg-1, respectively. The
      latter value is close to that of many petroleum fractions. This high-energy bio
      oil is therefore a clean fuel precursor and can be upgraded into higher quality
      fuels.

PMID- 27895289
TI  - Management, prevention and treatment of canine leishmaniosis in north-eastern
      Spain: an online questionnaire-based survey in the province of Girona with
      special emphasis on new preventive methods (CaniLeish vaccine and domperidone).
AB  - Knowledge of how canine leishmaniosis (CanL) is being managed clinically and its
      epidemiology is very important, since dogs are the main reservoir of human
      leishmaniosis. This study reports the results obtained through a questionnaire
      based survey of veterinary practitioners in Girona province, a recognised, but
      non-documented endemic area in north-eastern Spain. The primary objective was to
      obtain data on the clinical management of CanL, focusing particularly on new
      preventive methods and therapeutic tools. The results show an extensive routine
      management of CanL cases and a widespread use of the CaniLeish (Virbac) vaccine
      and domperidone (Leisguard, Esteve). Adverse reactions were detected by a vast
      majority of the vaccine users (82 per cent), the most frequent being local
      reactions, apathy, fever and gastroenteritis. All the respondents had treated
      confirmed cases, and the therapeutic protocol most used was the combination of
      meglumine antimoniate (Glucantime, Merial) and allopurinol (Zyloric,
      GlaxoSmithKline).

PMID- 27895288
TI  - Some biological activities of pigments extracted from Micrococcus roseus (PTCC
      1411) and Rhodotorula glutinis (PTCC 5257).
AB  - The importance of replacing synthetic pigments with natural types is increasing
      day by day in the food industry due to the harmful effects of some synthetic
      pigments. Microorganisms are a major source of natural pigments, which nowadays
      have attracted the attention of researchers. In this study, carotenoid pigments
      were produced by Micrococcus roseus and Rhodotorula glutinis, and some of their
      biological properties such as antimicrobial, antioxidant, anticancer, and anti
      inflammatory activities were evaluated. Given the results, bacteria, especially
      gram-positive bacteria, had higher sensitivity to the pigments extracted from M.
      roseus (PEM) and R. glutinis (PER) compared to molds so that Bacillus cereus and
      Alternaria citri had the highest and the lowest sensitivity, respectively. PER
      showed a higher antioxidant activity compared with PEM in the various methods of
      measuring antioxidant activity. In vitro and in vivo anti-tumor-promoting
      activities of PER were measured significantly more than PEM (P <0.05). Both
      pigment extracts remarkably inhibited the 12-O-tetradecanoylphorbol-13-acetate
      (TPA)-induced inflammation, so that ID50 (50% inhibitory dose) of PEM and PER
      were 0.22 and 0.09 mg/ear, respectively.

PMID- 27895287
TI  - Sudden sensorineural hearing loss: Is there a connection with inner ear
      electrolytic disorders? A literature review.
AB  - Electrolytic disorders of the inner ear represent a model that could be
      implicated in partially explaining the pathogenesis of sudden sensorineural
      hearing loss (SSNHL). Different types of electrolytes and different inner-ear
      loci are involved in cochlear homeostasis physiologically, to ensure the
      maintenance of an ion-balanced cochlear environment allowing a normal hair cell
      function. It has been hypothesized that a sudden loss of endocochlear potential,
      due to a rapid disruption of the inner ear fluid osmolality, could be responsible
      for a deterioration of the hearing function caused by damaged hair cells. The aim
      of this paper was to review the current literature and identify sources which
      might validate/fortify the hypothesis that inner ear electrolytic disorders have
      a role in the etiopathogenesis of SSNHL. The data in the literature underline the
      importance of ionic homeostasis in the inner ear, but they do not support a
      direct link between SSNHL and electrolyte disorders/imbalances. There is marginal
      evidence from otoacoustic emissions research that an indirect link might be
      present.

PMID- 27895291
TI  - Fewer Statistical Tests ... or Better Ones?

PMID- 27895290
TI  - Comparison of phenotypic and genotypic profiles among caprine and ovine
      Mycoplasma ovipneumoniae strains.
AB  - Mycoplasma ovipneumoniae (Movp) is considered to be one of the most important
      mycoplasmas causing respiratory disease in small ruminants. Most epidemiologic
      and characterisation studies have been conducted on strains collected from sheep.
      Information on the presence and characteristics of Movp in healthy and pneumonic
      goats is limited. Phenotypic or genotypic differences between sheep and goat
      isolates have never been studied. The objective of our study was to characterise
      and compare the similarities and differences between caprine and ovine Movp
      strains isolated from affected and asymptomatic animals in order to elucidate
      phenotypic and genotypic variability. Four different techniques were used on a
      set of 23 Movp isolates. These included SDS-PAGE, Western blotting, random
      amplified polymorphic DNA and the heat shock protein 70 gene sequence-based
      method. A high degree of phenotypic and genotypic heterogeneity among Movp
      strains was demonstrated in this study. Our results demonstrated differences
      between goat and sheep strains, revealing not only a link between strains and
      host ruminant species, but by geographical origin as well. However, the finding
      of immunodominant antigens of molecular masses 36, 38, 40 and 70 kDa (+/-3 kDa)
      in Movp isolates from sheep and goats foretells their potential use in the
      development of serological diagnostic tests and vaccines.

PMID- 27895292
TI  - Attention-Deficit Hyperactivity Disorder-Like Traits and Distractibility in the
      Visual Periphery.
AB  - We examined the performance of nonclinical subjects with high and low levels of
      self-reported attention-deficit hyperactivity disorder (ADHD)-like traits in a
      novel distractibility paradigm with far peripheral visual distractors, the likely
      origin of many distractors in everyday life. Subjects were tested on a Sustained
      Attention to Response Task with distractors appearing before some of the target
      or nontarget stimuli. When the distractors appeared 80 ms before the targets or
      nontargets, participants with high levels of ADHD-like traits were less affected
      in their reaction times than those with lower levels. Reducing the distractor
      target or nontarget interval to 10 ms removed the reaction time advantage for the
      high group. We suggest that at 80 ms, the distractors were cueing the arrival of
      the target or nontarget, and that those with high levels of ADHD-like traits were
      more sensitive to the cues. Increased sensitivity to stimuli in the visual
      periphery is consistent with hyperresponsiveness at the level of the superior
      colliculus.

PMID- 27895293
TI  - The Journal, the editor and the way ahead.

PMID- 27895295
TI  - Abstracts from the Scottish Paediatric Society St Andrew's Day Paediatric
      Symposium: Royal College of Physicians of Edinburgh, Edinburgh, Friday 27
      November 2015.

PMID- 27895294
TI  -  ... Is The 9:1 contract legal?

PMID- 27895297
TI  - Power of an Adaptive Trial Design for Endovascular Stroke Studies: Simulations
      Using IMS (Interventional Management of Stroke) III Data.
AB  - BACKGROUND AND PURPOSE: Adaptive trial designs that allow enrichment of the study
      population through subgroup selection can increase the chance of a positive trial
      when there is a differential treatment effect among patient subgroups. The goal
      of this study is to illustrate the potential benefit of adaptive subgroup
      selection in endovascular stroke studies. METHODS: We simulated the performance
      of a trial design with adaptive subgroup selection and compared it with that of a
      traditional design. Outcome data were based on 90-day modified Rankin Scale
      scores, observed in IMS III (Interventional Management of Stroke III), among
      patients with a vessel occlusion on baseline computed tomographic angiography
      (n=382). Patients were categorized based on 2 methods: (1) according to location
      of the arterial occlusive lesion and onset-to-randomization time and (2)
      according to onset-to-randomization time alone. The power to demonstrate a
      treatment benefit was based on 10 000 trial simulations for each design. RESULTS:
      The treatment effect was relatively homogeneous across categories when patients
      were categorized based on arterial occlusive lesion and time. Consequently, the
      adaptive design had similar power (47%) compared with the fixed trial design
      (45%). There was a differential treatment effect when patients were categorized
      based on time alone, resulting in greater power with the adaptive design (82%)
      than with the fixed design (57%). CONCLUSIONS: These simulations, based on real
      world patient data, indicate that adaptive subgroup selection has merit in
      endovascular stroke trials as it substantially increases power when the treatment
      effect differs among subgroups in a predicted pattern.

PMID- 27895298
TI  - Effect of Right Insular Involvement on Death and Functional Outcome After Acute
      Ischemic Stroke in the IST-3 Trial (Third International Stroke Trial).
AB  - BACKGROUND AND PURPOSE: In patients with acute ischemic stroke, whether
      involvement of the insular cortex influences outcome is controversial. Much of
      the apparent adverse outcome may relate to such strokes usually being severe. We
      examined the influence of right and left insular involvement on stroke outcomes
      among patients from the IST-3 study (Third International Stroke Trial) who had
      visible ischemic stroke on neuroimaging. METHODS: We used multiple logistic
      regression to compare outcomes of left versus right insular and noninsular
      strokes across strata of stroke severity, on death, proportion dead or dependent,
      and level of disability (ordinalized Oxford Handicap Score) at 6 months, with
      adjustment for the effects of age, lesion size, and presence of atrial
      fibrillation. RESULTS: Of 3035 patients recruited, 2099 had visible ischemic
      strokes limited to a single hemisphere on computed tomography/magnetic resonance
      scans. Of these, 566 and 714 had infarction of right and left insula. Six months
      after randomization, right insular involvement was associated with increased odds
      of death when compared with noninsular strokes on the left side (adjusted odds
      ratio, 1.83; 95% confidence interval, 1.33-2.52), whereas the adjusted odds ratio
      comparing mortality after insular versus noninsular strokes on the left side was
      not significant. Among mild/moderate strokes, outcomes for right insular
      involvement were worse than for left insular, but among more severe strokes, the
      difference in outcomes was less substantial. CONCLUSIONS: We found an association
      between right insular involvement and higher odds of death and worse functional
      outcome. The difference between right- and left-sided insular lesions on outcomes
      seemed to be most evident for mild/moderate strokes. CLINICAL TRIAL REGISTRATION:
      URL: http://www.isrctn.com. Unique identifier: ISRCTN25765518.

PMID- 27895299
TI  - Optimal Computed Tomographic Perfusion Scan Duration for Assessment of Acute
      Stroke Lesion Volumes.
AB  - BACKGROUND AND PURPOSE: The minimal scan duration needed to obtain reliable
      lesion volumes with computed tomographic perfusion (CTP) has not been well
      established in the literature. METHODS: We retrospectively assessed the impact of
      gradual truncation of the scan duration on acute ischemic lesion volume
      measurements. For each scan, we identified its optimal scan time, defined as the
      shortest scan duration that yields measurements of the ischemic lesion volumes
      similar to those obtained with longer scanning, and the relative height of the
      fitted venous output function at its optimal scan time. RESULTS: We analyzed 70
      computed tomographic perfusion scans of acute stroke patients. An optimal scan
      time could not be determined in 11 scans (16%). For the other 59 scans, the
      median optimal scan time was 32.7 seconds (90th percentile 52.6 seconds; 100th
      percentile 68.9 seconds), and the median relative height of the fitted venous
      output function at the optimal scan times was 0.39 (90th percentile 0.02; 100th
      percentile 0.00). On the basis of a linear model, the optimal scan time was T0
      plus 1.6 times the width of the venous output function (P<0.001; R2=0.49).
      CONCLUSIONS: This study shows how the optimal duration of a computed tomographic
      perfusion scan relates to the arrival time and width of the contrast bolus. This
      knowledge can be used to optimize computed tomographic perfusion scan protocols
      and to determine whether a scan is of sufficient duration. Provided a baseline
      (T0) of 10 seconds, a total scan duration of 60 to 70 seconds, which includes the
      entire downslope of the venous output function in most patients, is recommended.

PMID- 27895301
TI  - Acute Blood Pressure Management in Intracerebral Hemorrhage: Equipoise Resists an
      Attack.

PMID- 27895300
TI  - THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the
      Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage.
AB  - BACKGROUND AND PURPOSE: A ruptured intracranial aneurysm (IA) is the leading
      cause of a subarachnoid hemorrhage. This study seeks to define a specific gene
      whose mutation leads to disease. METHODS: More than 500 IA probands and 100
      affected families were enrolled and clinically characterized. Whole exome
      sequencing was performed on a large family, revealing a segregating THSD1
      (thrombospondin type 1 domain containing protein 1) mutation. THSD1 was sequenced
      in other probands and controls. Thsd1 loss-of-function studies in zebrafish and
      mice were used for in vivo analyses and functional studies performed using an in
      vitro endothelial cell model. RESULTS: A nonsense mutation in THSD1 was
      identified that segregated with the 9 affected (3 suffered subarachnoid
      hemorrhage and 6 had unruptured IA) and was absent in 13 unaffected family
      members (LOD score 4.69). Targeted THSD1 sequencing identified mutations in 8 of
      507 unrelated IA probands, including 3 who had suffered subarachnoid hemorrhage
      (1.6% [95% confidence interval, 0.8%-3.1%]). These THSD1 mutations/rare variants
      were highly enriched in our IA patient cohort relative to 89 040 chromosomes in
      Exome Aggregation Consortium (ExAC) database (P<0.0001). In zebrafish and mice,
      Thsd1 loss-of-function caused cerebral bleeding (which localized to the
      subarachnoid space in mice) and increased mortality. Mechanistically, THSD1 loss
      impaired endothelial cell focal adhesion to the basement membrane. These adhesion
      defects could be rescued by expression of wild-type THSD1 but not THSD1 mutants
      identified in IA patients. CONCLUSIONS: This report identifies THSD1 mutations in
      familial and sporadic IA patients and shows that THSD1 loss results in cerebral
      bleeding in 2 animal models. This finding provides new insight into IA and
      subarachnoid hemorrhage pathogenesis and provides new understanding of THSD1
      function, which includes endothelial cell to extracellular matrix adhesion.

PMID- 27895302
TI  - Self-Management Programs for Quality of Life in People With Stroke.

PMID- 27895303
TI  - Letter by Clark Regarding Article, "Clinical Outcomes of Transplanted Modified
      Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1/2a Study".

PMID- 27895304
TI  - Response by Steinberg et al to Letter Regarding Article, "Clinical Outcomes of
      Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A
      Phase 1/2A Study".

PMID- 27895305
TI  - Correction.

PMID- 27895306
TI  - Correction.

PMID- 27895307
TI  - Correction.

PMID- 27895308
TI  - Epigenetic inhibition of miR-663b by long non-coding RNA HOTAIR promotes
      pancreatic cancer cell proliferation via up-regulation of insulin-like growth
      factor 2.
AB  - Pancreatic cancer is one of the most deadly cancers with a poor prognosis.
      Although microRNAs are involving in the carcinogenesis and development of
      pancreatic cancer, little information is known regarding the role of miR-663b in
      pancreatic cancer. In this study, the expression of miR-663b in pancreatic cancer
      cells was down-regulated by hypermethylation in its putative promoter region, and
      overexpression of miR-663b repressed cell proliferation, invasion and migration,
      and induced apoptosis in pancreatic cancer cells. Bioinformatics analysis,
      luciferase report assay and rescue experiments showed that insulin-like growth
      factor 2 (IGF2) was a direct target of miR-663b. Results from clinical samples
      showed that the expression level of miR-663b correlated with the pathological
      grading, and the expression of miR-663b was down-regulated and was inversely
      correlated with IGF2 expression level in pancreatic cancer tissues. More
      importantly, the long non-coding RNA, HOX transcript antisense RNA (HOTAIR), was
      up-regulated in both pancreatic cancer cells and tissues, and HOTAIR suppressed
      the expression of miR-663b in pancreatic cancer by histone modification on
      H3K4me3 and H3K27me3 on miR-663b promoter. Further in vivo studies demonstrated
      that the stable overexpression of miR-663b or knock-down of HOTAIR inhibited
      tumor growth and was associated with IGF2 expression. In summary, our studies
      demonstrated that miR-663b is epigenetically repressed by HOTAIR and exerts its
      tumor-suppressive function via targeting IGF2 in pancreatic cancer.

PMID- 27895311
TI  - Aging of hippocampal neurogenesis and soy isoflavone.

PMID- 27895310
TI  - TGFbeta1 overexpression is associated with improved survival and low tumor cell
      proliferation in patients with early-stage pancreatic ductal adenocarcinoma.
AB  - The role of transforming growth factor beta-type-1 (TGFbeta1) in pancreatic
      ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that
      TGFbeta1 expression is associated with survival and proliferation markers in
      patients with early-stage PDAC. We acquired clinicopathologic, treatment, and
      mRNA expression data from The Cancer Genome Atlas data set for 106 patients
      identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients
      were categorized as high expression when mRNA expression was >=75th percentile
      for each gene. Average log2 mRNA expression of TGFbeta1 in patients with high
      expression was 11.6 +/- 0.2 and 10.5 +/- 0.6 in patients with low expression
      (P<0.001). Low TGFbeta1 expression is associated with shorter median survival
      compared with high TGFbeta1 expression (17 versus at least 60 months; P=0.005).
      Patients with tumors demonstrating high MKI67 (the gene encoding Ki-67)
      expression have shorter median survival versus those with lowerMKI67 expression
      (16 versus 20 months; P=0.026). TGFbeta1 and MKI67 are inversely associated
      (P=0.009). On multivariate analysis, improved survival is associated with
      TGFbeta1 overexpression (P=0.017), adjuvant chemotherapy (P=0.001), and adjuvant
      radiotherapy (P=0.017), whereas positive surgical margins are associated with
      worse survival (P=0.002). In patients who undergo pancreaticoduodenectomy for
      PDAC, high TGFbeta1 expression may counteract the worse survival associated with
      high proliferation.

PMID- 27895309
TI  - Hepatocyte specific expression of an oncogenic variant of beta-catenin results in
      cholestatic liver disease.
AB  - BACKGROUND: The Wnt/beta-catenin signaling pathway plays a crucial role in
      embryonic development, tissue homeostasis, wound healing and malignant
      transformation in different organs including the liver. The consequences of
      continuous beta-catenin signaling in hepatocytes remain elusive. RESULTS: Livers
      of Ctnnb1CA hep mice were characterized by disturbed liver architecture,
      proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile
      acid levels were significantly increased in Ctnnb1CA hep mice. The primary bile
      acid synthesis enzyme Cyp7a1 was increased whereas Cyp27 and Cyp8b1 were reduced
      in Ctnnb1CA hep mice. Expression of compensatory bile acid transporters including
      Abcb1, Abcb4, Abcc2 and Abcc4 were significantly increased in Ctnnb1CA hep mice
      while Ntcp was reduced. Accompanying changes of bile acid transporters favoring
      excretion of bile acids were observed in intestine and kidneys of Ctnnb1CA hep
      mice. Additionally, disturbed bile acid regulation through the FXR-FGF15-FGFR4
      pathway was observed in mice with activated beta-catenin. MATERIALS AND METHODS:
      Mice with a loxP-flanked exon 3 of the Ctnnb1 gene were crossed to Albumin-Cre
      mice to obtain mice with hepatocyte-specific expression of a dominant stable form
      of beta-catenin (Ctnnb1CA hep mice). Ctnnb1CA hep mice were analyzed by
      histology, serum biochemistry and mRNA profiling. CONCLUSIONS: Expression of a
      dominant stable form of beta-catenin in hepatocytes results in severe cholestasis
      and biliary type fibrosis.

PMID- 27895312
TI  - Activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway in
      human lung cancer cells by the new synthetic flavonoid, LZ-205.
AB  - It has been shown that flavonoids have anti-tumor activity. In this study, LZ
      205, a newly synthesized flavonoid, was found to be effective in inducing
      apoptosis in human lung cancer cells in vivo and in vitro. Mechanistically, LZ
      205 triggers reactive oxygen species (ROS)-induced endoplasmic reticulum (ER)
      stress and unfolded protein response, which could be reversed by silencing CHOP,
      a mediator of the ER stress-associated apoptosis. In addition, LZ-205-induced
      apoptosis is accompanied by the activation of both the mitochondrial apoptotic
      and extrinsic pathways, followed by decreased mitochondrial membrane potential
      (DeltaPsim) and the alteration of the expression of mitochondria-related pro- and
      anti-apoptotic proteins. LZ-205 exhibits a potential antitumor effect in BALB/c
      nude mice bearing H460 tumor with low systemic toxicity. In summary, both the ROS
      mediated ER stress pathway and the exogenous apoptotic pathway are involved in LZ
      205-induced apoptosis in vitro and in vivo. Our data show a therapeutic potential
      of LZ-205 for the treatment of lung cancer.

PMID- 27895314
TI  - Quantitative assessment of background parenchymal enhancement in breast magnetic
      resonance images predicts the risk of breast cancer.
AB  - The objective of this study was to evaluate the association betweenthe
      quantitative assessment of background parenchymal enhancement rate (BPER) and
      breast cancer. From 14,033 consecutive patients who underwent breast MRI in our
      center, we randomly selected 101 normal controls. Then, we selected 101 women
      with benign breast lesions and 101 women with breast cancer who were matched for
      age and menstruation status. We evaluated BPER at early (2 minutes), medium (4
      minutes) and late (6 minutes) enhanced time phases of breast MRI for quantitative
      assessment. Odds ratios (ORs) for risk of breast cancer were calculated using the
      receiver operating curve. The BPER increased in a time-dependent manner after
      enhancement in both premenopausal and postmenopausal women. Premenopausal women
      had higher BPER than postmenopausal women at early, medium and late enhanced
      phases. In the normal population, the OR for probability of breast cancer for
      premenopausal women with high BPER was 4.1 (95% CI: 1.7-9.7) and 4.6 (95% CI: 1.7
      12.0) for postmenopausal women. The OR of breast cancer morbidity in
      premenopausal women with high BPER was 2.6 (95% CI: 1.1-6.4) and 2.8 (95% CI: 1.2
      6.1) for postmenopausal women. The BPER was found to be a predictive factor of
      breast cancer morbidity. Different time phases should be used to assess BPER in
      premenopausal and postmenopausal women.

PMID- 27895313
TI  - Repurposing the anti-malarial drug dihydroartemisinin suppresses metastasis of
      non-small-cell lung cancer via inhibiting NF-kappaB/GLUT1 axis.
AB  - Non-small-cell lung cancer (NSCLC) is an aggressive malignancy and long-term
      survival remains unsatisfactory for patients with metastatic and recurrent
      disease. Repurposing the anti-malarial drug dihydroartemisinin (DHA) has been
      proved to possess potent antitumor effect on various cancers. However, the
      effects of DHA in preventing the invasion of NSCLC cells have not been studied.
      In the present study, we determined the inhibitory effects of DHA on invasion and
      migration and the possible mechanisms involved using A549 and H1975 cells. DHA
      inhibited in vitro migration and invasion of NSCLC cells even in low
      concentration with little cytotoxicity. Additionally, low concentration DHA also
      inhibited Warburg effect in NSCLC cells. Mechanically, DHA negatively regulates
      NF-kappaB signaling to inhibit the GLUT1 translocation. Blocking the NF-kappaB
      signaling largely abolishes the inhibitory effects of DHA on the translocation of
      GLUT1 to the plasma membrane and the Warburg effect. Furthermore, GLUT1 knockdown
      significantly decreased the inhibition of invasion, and migration by DHA. Our
      results suggested that DHA can inhibit metastasis of NSCLC by targeting glucose
      metabolism via inhibiting NF-kappaB signaling pathway and DHA may deserve further
      investigation in NSCLC treatment.

PMID- 27895315
TI  - Identification of aberrantly expressed glycans in gastric cancer by integrated
      lectin microarray and mass spectrometric analyses.
AB  - Cancer progression is usually associated with alterations of glycan expression
      patterns. Little is known regarding global glycomics in gastric cancer, the most
      common type of epithelial cancer. We integrated lectin microarray and mass
      spectrometry (MS) methods to profile glycan expression in three gastric cancer
      cell lines (SGC-7901, HGC-27, and MGC-803) and one normal gastric epithelial cell
      line (GES-1). Significantly altered glycans were confirmed by lectin staining and
      MALDI-TOF/TOF-MS. The three cancer cell lines showed increased levels of core
      fucosylated N-glycans, GalNAcalpha-Ser/Thr (Tn antigen), and Sia2-6Galbeta1
      4GlcNAc N-glycans, but reduced levels of biantennary N-glycans, Galbeta1
      3GalNAcalpha-Ser/Thr (T antigen), and (GlcNAc)n N-glycans. Lectin histochemistry
      was used to validate aberrant expression of four representative glycans (core
      fucosylation, Sia2-6Galbeta1-4GlcNAc, biantennary N-glycans, T antigen,
      recognized respectively by lectins LCA, SNA, PHA-E+L, and ACA) in clinical
      gastric cancer samples. Lower binding capacity for ACA was correlated with
      significantly poorer patient prognosis. Our findings indicate for the first time
      that glycans recognized by LCA, ACA, and PHA-E+L are aberrantly expressed in
      gastric cancer, and suggest that ACA is a potential prognostic factor for gastric
      cancer.

PMID- 27895316
TI  - Investigating cytokinesis failure as a strategy in cancer therapy.
AB  - Effective therapeutics exploit common characteristics shared amongst cancers. As
      many cancers present chromosomal instability (CIN), one possible approach to
      treat these cancers could be to increase their CIN above a threshold that would
      affect their viability. Here, we investigated whether causing polyploidy by
      cytokinesis failure could represent a useful approach. We show that cytokinesis
      failure caused by depletion of Citron kinase (CIT-K) dramatically decreased cell
      proliferation in breast, cervical and colorectal cancer cells. CIT-K depletion
      activated the Hippo tumor suppressor pathway in normal, but not in cancer cells,
      indicating that cancer cells have evolved mechanisms to bypass this control. CIT
      K depleted cancer cells died via apoptosis in a caspase 7 dependent manner and,
      consistent with this, p53-deficient HCT116 colon carcinoma cells failed to induce
      apoptosis after cytokinesis failure. However, other p53-mutated cancer cells were
      able to initiate apoptosis, indicating that cytokinesis failure can trigger
      apoptosis through a p53-independent mechanism. Finally, we found that actively
      dividing and, in some cases, polyploid cancer cells were more susceptible to CIT
      K depletion. In sum, our findings indicate that inducing cytokinesis failure
      could be a promising anti-cancer therapeutic approach for a wide range of
      cancers, especially those characterized by fast cell proliferation and
      polyploidy.

PMID- 27895317
TI  - IL-4, a direct target of miR-340/429, is involved in radiation-induced aggressive
      tumor behavior in human carcinoma cells.
AB  - Radiotherapy induces the production of cytokines, thereby increasing aggressive
      tumor behavior. This radiation effect results in the failure of radiotherapy and
      increases the mortality rate in patients. We found that interleukin-4 (IL-4) and
      IL-4Ralpha (IL-4 receptor) are highly expressed in various human cancer cells
      subsequent to radiation treatment. In addition, IL-4 is highly overexpressed in
      metastatic carcinoma tissues compared with infiltrating carcinoma tissues. High
      expression of IL-4 in patients with cancer is strongly correlated with poor
      survival. The results of this study suggest that radiation-induced IL-4
      contributes to tumor progression and metastasis. Radiation-induced IL-4 was
      associated with tumorigenicity and metastasis. IL-4 expression was downregulated
      by miR-340 and miR-429, which were decreased by ionizing radiation (IR).
      Radiation-regulated miR-340/429-IL4 signaling increased tumorigenesis and
      metastasis by inducing the production of Sox2, Vimentin, VEGF, Ang2, and MMP-2/9
      via activating JAK, JNK, beta-catenin, and Stat6 in vitro and in vivo. Our study
      presents a conceptual advance in our understanding of the modification of tumor
      microenvironment by radiation and suggests that combining radiotherapy with
      genetic therapy to inhibit IL-4 may be a promising strategy for preventing post
      radiation recurrence and metastasis in patients.

PMID- 27895319
TI  - Activation of chronic toxoplasmosis by transportation stress in a mouse model.
AB  - Toxoplasma gondii is an obligate intracellular parasite infecting 25% of the
      world population and enormous number of animals. It can exist in two forms in
      intermediate hosts: the fast replicating tachyzoites responsible for acute
      infection and the slowly replicating bradyzoites responsible for life-long
      chronic infection. The interconversion between tachyzoites and bradyzoites plays
      critical roles in the transmission and pathogenesis of T. gondii. However, the
      molecular mechanisms that govern the interconversion are largely unknown. In this
      study, we established a chronic infection model in mice and examined the impact
      of transportation stress on the status of chronic infection. Our results
      demonstrated that, treating chronically infected mice with conditions mimicking
      transportation stress reduced the levels of several key cytokines that restrict
      the infection at chronic stage. Increased expression of the tachyzoite specific
      gene SAG1 (surface antigen 1) was detected in brain cysts of stress treated mice,
      indicating activation and conversion of bradyzoites to tachyzoites. Using this
      model, we identified fifteen toxoplasmic proteins that had significant abundance
      changes during stress induced cysts reactivation. These proteins serve as a basis
      for further investigation of the mechanisms governing bradyzoite conversion.

PMID- 27895318
TI  - Whole genome DNA methylation: beyond genes silencing.
AB  - The combination of DNA bisulfite treatment with high-throughput sequencing
      technologies has enabled investigation of genome-wide DNA methylation at near
      base pair level resolution, far beyond that of the kilobase-long canonical CpG
      islands that initially revealed the biological relevance of this covalent DNA
      modification. The latest high-resolution studies have revealed a role for very
      punctual DNA methylation in chromatin plasticity, gene regulation and splicing.
      Here, we aim to outline the major biological consequences of DNA methylation
      recently discovered. We also discuss the necessity of tuning DNA methylation
      resolution into an adequate scale to ease the integration of the methylome
      information with other chromatin features and transcription events such as gene
      expression, nucleosome positioning, transcription factors binding dynamic, gene
      splicing and genomic imprinting. Finally, our review sheds light on DNA
      methylation heterogeneity in cell population and the different approaches used
      for its assessment, including the contribution of single cell DNA analysis
      technology.

PMID- 27895320
TI  - Clinical Experience with Pancreas Graft Rescue From Severe Thrombus After
      Simultaneous Pancreas-Kidney Transplantation by Early Detection with Doppler
      Ultrasound: A Case Report.
AB  - BACKGROUND Graft thrombosis is the main cause of early graft loss after
      transplantation. In Japan, pancreases available for transplantation are
      frequently from marginal donors due to diverse backgrounds in the population.
      However, marginal tissues increase the risk of early thrombosis in the graft.
      CASE REPORT Here, we describe a 41-year-old woman with type 1 diabetes mellitus
      who underwent a simultaneous pancreas-kidney transplantation. The pancreas was
      retrieved from a 34-year-old man who had experienced severe hemodynamic
      instability. The pancreaticoduodenal graft was implanted in the recipient iliac
      fossa with enteric drainage. Although the patient had not shown any physical
      signs or alterations in substances that might indicate functional loss of the
      pancreas graft, a Doppler ultrasound analysis detected a major thrombus in the
      pancreas graft on day 7 after surgery. A thrombectomy was performed with a
      radiological emergent intervention. After percutaneous direct thrombolysis, the
      patient received adjuvant thrombolytic therapy. Thereafter, the postoperative
      course was uneventful and the pancreas graft remained functional. CONCLUSIONS
      Early detection and treatment of thromboses are required to avoid graft failure
      and graft pancreatectomy. This case study demonstrates that early detection of
      severe thrombus with Doppler ultrasound in a grafted pancreas did not increase
      the risk of graft failure.

PMID- 27895321
TI  - Is Nasal Polyposis Related to Levels of Serum Vitamin D and Vitamin D Receptor
      Gene Expression?
AB  - BACKGROUND Nasal polyposis (NP) is the most frequent cause of nasal masses.
      Despite considerable research on the subject, its etiology has not been fully
      elucidated, and effective treatment methods have not been developed. Some
      etiological factors causing low or high expression of genes in genetically
      predisposed individuals may play a role in the pathogenesis of the disease. The
      purpose of this study was to assess the relation between levels of vitamin D
      receptor (VDR) gene expression and serum vitamin D with NP. MATERIAL AND METHODS
      The study included 46 subjects with NP (NP group) and 40 volunteers (control
      group). Nasal polyp tissue samples were taken from the NP group and nasal mucosa
      samples were taken from the control group. Levels of VDR gene expression in the
      tissue samples were assessed using the real-time polymerase chain reaction (RT
      PCR) method. RESULTS Mean serum 25(OH)D levels were 13.38+/-14.08 ng/ml in the NP
      group and 10.57+/-6.44 ng/ml in the control group (p=0.249). VDR gene expression
      was present in 17.5% of the NP group and 3.3% of the control group, and the
      difference between the 2 groups was statistically significant (likelihood ratio
      chi2=3.887; p=0.049). CONCLUSIONS This is the first study to assess levels of VDR
      gene expression in subjects with NP. Our results suggest that VDR gene expression
      may be associated with the pathogenesis or progression of NP.

PMID- 27895324
TI  - Molecular genetic heterogeneity in undifferentiated endometrial carcinomas.

PMID- 27895322
TI  - Gestational vitamin D deficiency and autism-related traits: the Generation R
      Study.
AB  - There is intense interest in identifying modifiable risk factors associated with
      autism-spectrum disorders (ASD). Autism-related traits, which can be assessed in
      a continuous fashion, share risk factors with ASD, and thus can serve as
      informative phenotypes in population-based cohort studies. Based on the growing
      body of research linking gestational vitamin D deficiency with altered brain
      development, this common exposure is a candidate modifiable risk factor for ASD
      and autism-related traits. The association between gestational vitamin D
      deficiency and a continuous measure of autism-related traits at ~6 years (Social
      Responsiveness Scale; SRS) was determined in a large population-based cohort of
      mothers and their children (n=4229). 25-hydroxyvitamin D (25OHD) was assessed
      from maternal mid-gestation sera and from neonatal sera (collected from cord
      blood). Vitamin D deficiency was defined as 25OHD concentrations less than 25
      nmol l-1. Compared with the 25OHD sufficient group (25OHD>50 nmol l-1), those who
      were 25OHD deficient had significantly higher (more abnormal) SRS scores (mid
      gestation n=2866, beta=0.06, P<0.001; cord blood n=1712, beta=0.03, P=0.01). The
      findings persisted (a) when we restricted the models to offspring with European
      ancestry, (b) when we adjusted for sample structure using genetic data, (c) when
      25OHD was entered as a continuous measure in the models and (d) when we corrected
      for the effect of season of blood sampling. Gestational vitamin D deficiency was
      associated with autism-related traits in a large population-based sample. Because
      gestational vitamin D deficiency is readily preventable with safe, cheap and
      accessible supplements, this candidate risk factor warrants closer scrutiny.

PMID- 27895326
TI  - Carole Ho.

PMID- 27895327
TI  - Anticancer drugs: Breaking up a pro-survival interaction.

PMID- 27895323
TI  - Elevated CYP2C19 expression is associated with depressive symptoms and
      hippocampal homeostasis impairment.
AB  - The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is
      expressed in the adult liver and fetal brain. Previously, we demonstrated that
      the absence of CYP2C19 is associated with lower levels of depressive symptoms in
      1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG)
      have shown an anxious phenotype and decrease in hippocampal volume and adult
      neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG
      findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG
      strain as a tool for preclinical screening of new antidepressants and (3) provide
      an insight into the molecular underpinnings of the 2C19TG phenotype. In humans,
      we found that the absence of CYP2C19 was associated with a bilateral hippocampal
      volume increase in two independent healthy cohorts (N=386 and 1032) and a lower
      prevalence of major depressive disorder and depression severity in African
      Americans (N=3848). Moreover, genetically determined high CYP2C19 enzymatic
      capacity was associated with higher suicidality in depressed suicide attempters
      (N=209). 2C19TG mice showed high stress sensitivity, impaired hippocampal Bdnf
      homeostasis in stress, and more despair-like behavior in the forced swim test
      (FST). After the treatment with citalopram and 5-HT1A receptor agonist 8OH-DPAT,
      the reduction in immobility time in the FST was more pronounced in 2C19TG mice
      compared with WTs. Conversely, in the 2C19TG hippocampus, metabolic turnover of
      serotonin was reduced, whereas ERK1/2 and GSK3beta phosphorylation was increased.
      Altogether, this study indicates that elevated CYP2C19 expression is associated
      with depressive symptoms, reduced hippocampal volume and impairment of
      hippocampal serotonin and BDNF homeostasis.

PMID- 27895328
TI  - Regulatory watch: Challenges in drug development for central nervous system
      disorders: a European Medicines Agency perspective.

PMID- 27895329
TI  - Cancer immunology community seeks better end points.

PMID- 27895330
TI  - FDA approves antitoxin antibody.

PMID- 27895332
TI  - EMA opens its data vaults.

PMID- 27895331
TI  - Paring down the placebo response.

PMID- 27895333
TI  - Anticancer drugs: Exploiting a weakness in colorectal cancers.

PMID- 27895334
TI  - Biologics: Engineering T cells for customized therapeutic responses.

PMID- 27895335
TI  - PCSK9 pipeline.

PMID- 27895336
TI  - Access to medicines report cards.

PMID- 27895337
TI  - Equivalence of BCSH and WHO diagnostic criteria for ET.

PMID- 27895338
TI  - Response to Harrison et al. 'Clinically relevant differences between BCSH and WHO
      diagnostic criteria for ET'.

PMID- 27895339
TI  - Breast reconstruction at The Aga Khan University - A 10 year audit.
AB  - Considering the high incidence of breast cancer and the subsequent need for a
      mastectomy, the number of patients having breast reconstruction remains
      relatively low the world over. Most studies from the west show that anywhere
      between 5% to around 50% of women proceed to reconstruction following a complete
      mastectomy. There is a great paucity of literature on the subject in Pakistan.
      Anecdotal and unofficial accounts would suggest that less than a fraction of 1%
      of women in Pakistan undergo reconstruction following a mastectomy.We reviewed
      our cases retrospectively over a 10 year study period from January 2005 to
      December 2014 with the objective to assess our results and to learn from them as
      well as to attempt to raise the profile of this important reconstructive
      manoeuver. Our numbers are low when compared internationally. However on a
      national level it would seem that the numbers currently exceed most institutions
      in the country. The overall results appear to be acceptable though the low
      numbers preclude definitive conclusions.

PMID- 27895340
TI  - Is Grown Up Congenital Heart (GUCH) disease different in a developing country?
AB  - In the current era grown up congenital heart disease (GUCH) patients undergoing
      surgical interventions are increasing. Most of the interventions in the developed
      countries are either complex or redo-operations in patients who had previously
      undergone repair, palliation or correction. However, in the developing countries
      most of the interventions are primary and corrective. This descriptive
      retrospective study comprised GUCH patients who underwent surgical intervention
      for congenital heart disease (CHD) at Aga Khan University Hospital, Karachi, from
      January 2006 to December 2015. A total of 195 patients had been treated
      surgically with a mean age of 31.0+/-13.5 years. Majority of the patients
      underwent surgical interventions for closure of atrial 109(55.3%) and ventricular
      51(26.2%) septal defect. The most common complications were prolonged ventilation
      16(8.1%). Overall mortality was 4(2.1%). GUCH in our practice is for primary
      procedure with simple diagnosis that should have been treated before reaching
      adulthood as is done in the developed countries.

PMID- 27895341
TI  - Bringing efficiency into practice: A quality improvement initiative to reduce
      operating room turnaround time.
AB  - Operating room (OR) turnaround time (TAT) is the minimal essential time required
      for cleaning of OR and preparation for the next case. The TAT inversely affects
      OR efficiency. Several factors related to personnel, equipment and scheduling
      have been identified as causes of increased TAT. We conducted the study to
      identify factors that affect OR TAT and to propose recommendations for its
      reduction. The retrospective study, conducted at Aga Khan University Hospital,
      Karachi, comprised TAT records related to March 2014. Of the 88 cases, 22(25%)
      showed a delay. Upon Pareto analysis it was found that in 8(36.6%) cases there
      was a delay of 70% related to scheduling of OR list and 5(22.7%) related to
      movement of patients from wards to OR. As such, improvement in these two broad
      areas can take care of majority of delays. We also recommend documentation of all
      processes as part of continuous improvement.

PMID- 27895342
TI  - Innovations in cardiovascular care: Historical perspective, contemporary
      practice, recent trends and future directions.
AB  - Cardiovascular diseases continue to be a major cause of mortality and morbidity
      in the world population. First open heart procedure was performed by Gibbon in
      1953, since then many advancements have been introduced to the field of cardiac
      surgery. Minimally invasive techniques were introduced, which include minimally
      invasive coronary artery bypass grafting (CABG), off-pump technique, minimally
      invasive valve surgery or transcatheter techniques to implant stentless or
      sutureless valves. The hybrid strategy to address coronary disease combines
      catheterisation procedures with standard surgical techniques. Cardiac imaging has
      also progressed to provide three-dimensional images of the heart, enabling
      surgeons to plan procedures with greater accuracy. Left ventricular assist
      devices can be used in patients suffering from cardiogenic shock or awaiting
      heart transplantation. Total artificial heart can be used for biventricular
      mechanical support. As technology becomes increasingly used for patient
      management, the future surgeon needs to be trained in minimally invasive surgical
      techniques.

PMID- 27895343
TI  - Cervical mediastinoscopy in the diagnosis of lymphadenopathy in South Asia.
AB  - We planned to determine the clinical utility and safety of mediastinoscopy in the
      pathologic diagnosis of mediastinal lymphadenopathy and to determine disease
      patterns in a tertiary care setting in Karachi. The retrospective review
      comprised record of patients who underwent mediastinoscopy over 25 years between
      July, 1990 and August, 2015. Of the 122 patients, records were complete for
      88(72%). Mean age was 42.5+/-12.9 years and 55(62.5%) were male. Overall,
      60(68.2%) patients had benign inflammatory diseases; 25 (28.4%) had lymphoma or
      lung cancer which was accurately staged; 26(29.5%) had tuberculosis; 13(14.8%)
      sarcoidosis; and 11 (12.5%) had concomitant tuberculosis and sarcoidosis. No
      mortality or significant morbidity was recorded. Mediastinoscopy was useful in
      staging bronchogenic carcinoma and influenced the management in this series. It
      was found to be accurate in the diagnosis of other malignant as well as benign
      mediastinal pathologies, all of which were treatable.

PMID- 27895344
TI  - Peri-operative determinants of prolonged CICU stay after coronary artery bypass
      graft surgery in elderly at a private tertiary care hospital: A case control
      study.
AB  - OBJECTIVE: To explore peri-operative risk factors associated with prolonged stay
      in cardiac intensive care unit among patients undergoing isolated coronary artery
      bypass grafting. Methods: This retrospective case control study was conducted at
      the Aga Khan University Hospital, Karachi, comprised medical records of patients
      who had undergone cardiothoracic revascularisation surgery from January 2006 to
      December 2013. The patients were grouped into cases and controls at a ratio of
      1:2 on the basis of length of stay at cardiac intensive care unit, i.e. >72 hours
      and <72 hours. Independent risk factors for prolonged cardiac intensive care
      unitstay were evaluated. SPSS 20 was used for data analysis. Results: Of the 999
      patients, 333(33.3%) were cases and 666(66.6%) were controls. The mean age of
      cases was 62.5+/-9.7 years and that of controls was 60.8+/-9.6 years (p=0.007).
      The number of males was 280(84.1%) among the cases and 489(73.4%)among the
      controls. Adjusted odds ratio and 95% confidence interval for age and male gender
      were 1.02 (1.0,1.03) and [1.90 (1.32,2.74)]; diabetics were at high risk of
      staying longer [1.51 (1.13,2.02)]; previous cardiovascular interventions [1.65
      (1.05,2.59)], intra-aortic balloon pump insertion [1.45 (1.01,2.08)], initial
      ventilation time and post-operative bleeding tamponade were independently
      associated with prolonged cardiac intensive care unit stay [1.01 (1.00, 1.01)]
      and [1.9 (1.13,3.2)], respectively. The risk of dying among the cases was three
      times more after adjusting for all covariates in the model [3.1 (1.52,6.31)].
      Conclusion: Advanced age, male gender, diabetes, previous cardiovascular
      interventions, post-operative intra-aortic balloon pump insertion, initial
      ventilation support and post-op bleeding tamponade were found to be the
      independent risk factors for prolonged cardiac intensive care unit stay.

PMID- 27895345
TI  - A review of the failed cases of dental implants at a university hospital in
      Karachi, Pakistan.
AB  - The retrospective study was conducted to assess the dental implants that
      experienced failure. It was conducted at the dental clinic of the Aga Khan
      University Hospital, Karachi, and comprised record of dental implants from July
      2010 to June 2015. Variables such as patient age, gender and systemic status,
      length and diameter of implants, bone grafting, type of definitive prosthesis
      (crown or bridge or overdenture), nature of retention (cement versus screw
      retained), loading strategy (immediate versus delayed loading), etc. were
      analysed. Of the 220 implants placed, 6(2.7%) failed to integrate (as revealed by
      torque test) at the beginning of prosthetic phase. Besides, 1(0.5%) implant
      failed after six months of function. The 7(3.2%) failed cases had common
      variables like deficient bone volume in maxilla (or placement of bone graft), non
      submerged placement protocol, early loading with prosthesis and the presence of
      diabetes.

PMID- 27895346
TI  - Association between hypodontia and Angles malocclusion.
AB  - This study was planned to determine the prevalence of hypodontia in permanent
      dentition and to test whether an association was present between hypodontia and
      Angle's malocclusion. The retrospective study was conducted at a tertiary care
      hospital, Karachi, and comprised record of all patients visiting the orthodontic
      clinics of the hospital from 2005 to 2015. Orthodontic records of 790(79%)
      subjects, including 189(23.9%) males and 601(76.1%) females, were reviewed. Their
      mean age was 17 +/- 5.06 years. A tooth was considered missing if no evidence of
      tooth germ was observed on orthopantomograms and dental casts. The total sample
      was distributed into three groups on the basis of Angle's classification. Chi
      square test was applied to determine an association between hypodontia and
      Angle's malocclusion. Tooth agenesis was observed in 34(4.3%) and a statistically
      significant difference was found between the genders (p=0.005). A positive
      association was found between hypodontia and malocclusion groups. Higher
      frequency of missing teeth was seen in Class III malocclusion which indicates a
      great need for orthodontic treatment as it has a psychosocial impact on the
      quality of life.

PMID- 27895347
TI  - Comparison of fracture and deformation in the rotary endodontic instruments:
      Protaper versus K-3 system.
AB  - This experimental study was done on extracted human teeth to compare the fracture
      and deformation of the two rotary endodontic files system namely K-3 and
      Protapers. It was conducted at the dental clinics of the Aga Khan University
      Hospital, Karachi, A log of file deformation or fracture during root canal
      preparation was kept. The location of fracture was noted along with the identity
      of the canal in which fracture took place. The fracture in the two rotary systems
      was compared. SPSS 20 was used for data analysis. Of the 172(80.4%) teeth
      possessing more than 15 degrees of curvature, fracture occurred in 7(4.1%) cases
      and deformation in 10(5.8%). Of the 42(19.6%) teeth possessing less than 15
      degrees of curvature, fracture occurred in none of them while deformation was
      seen in 1(2.4%). There was no difference in K-3 and Protaper files with respect
      to file deformation and fracture. Most of the fractures occurred in mesiobuccal
      canals of maxillary molars, n=3(21.4%). The likelihood of file fracture increased
      5.65-fold when the same file was used more than 3 times. Irrespective of the
      rotary system, apical third of the root canal space was the most common site for
      file fracture.

PMID- 27895348
TI  - A 6-year Evaluation of 223 Tapered Dental Implants and associated prosthesis in
      92 patients at a University Hospital.
AB  - The aim of the retrospective study was to assess the clinical and radiographic
      outcome of the dental implant surgery and prosthetics. It was conducted at the
      Aga Khan University Hospital, Karachi, and comprised of medical charts and
      radiographic records of patients visiting between 2010 and 2015. Variables such
      as implant dimensions, final prosthesis, method of retention, loading protocol
      and patient factors were analysed. A total of 223 implants (143(64.1%) in maxilla
      and 80(35.9%) in mandible) were placed in 92 subjects (50(54.3%) males and
      42(45.7%) females). All implants were Zimmer tapered screw-vent. Length of
      108(48.4%) implants was 11.5mm and diameter of 84(37.7%) implants was 4.7mm.
      Besides, 6(2.7%) implants failed to osseointegrate, whereas 1(0.4%) implant
      failed at 12 months of loading. Among the 216(96.9%) successful implants,
      140(64.8%) served as bridge abutments, 72(33.3%) were single crown abutments and
      4(1.9%) were overdenture abutments. Also, 37(17.1%) implants were immediately
      loaded. The six-year survival rate of implants was 96.9%.

PMID- 27895349
TI  - Prevalence of musculoskeletal disorders among dentists in teaching hospitals in
      Karachi, Pakistan.
AB  - Work-related musculoskeletal pain is common among healthcare professionals,
      including dentists. This cross-sectional study was conducted to determine the
      prevalence of work-related musculoskeletal disorders (MSDs) among dentists. This
      study was carried out from January to April 2016 at various teaching hospitals of
      Karachi, and comprised 230 dentists. A self-administered questionnaire, adapted
      from a validated Nordic questionnaire, was distributed among the participants.
      Descriptive statistics were computed and associations of interest were analysed
      using chi-square test. Of the 230 forms, 182(79.11%) were included after leaving
      out the incomplete ones. The overall prevalence of MSDs was 138(75.8%). The most
      frequent reasons for MSDs were lack of rest 21(15.2%) and having static postures
      for more than half-an-hour per procedure 38(27.5%).

PMID- 27895350
TI  - Age estimation of a sample of Pakistani population using Coronal Pulp Cavity
      Index in molars and premolars on Orthopantomogram.
AB  - The aim of the present study was to assess the validity of tooth-coronal index
      (TCI) in the age estimation. This retrospective charts review was conducted at
      the Aga Khan University Hospital, Karachi from January 2016 to March 2016, and
      comprised 315 teeth of 80 individuals. The teeth were analysed on
      Orthopantomogram. TCI was calculated for unrestored mandibular premolars and
      molars. Pearson???'s correlation was applied to assess correlation between
      chronological age and TCI. Besides, 30(37.5%) subjects were male and 50(62.5%)
      female, and 140(44.4%) teeth were of male subjects and 175(55.6%) were of
      females. The mean correlation coefficient between chronological age and TCI was 
      0.27. The highest negative correlation was observed for tooth No.47 in males (r=
      0.72) whereas among females the highest negative correlation was noted for tooth
      No.36 (r=-0.61).There was very weak correlation between age and TCI of a tooth.
      Therefore, TCI index could not be predictably used for age estimation in the
      studied population.

PMID- 27895351
TI  - Frequency of Sensorineural hearing loss in chronic suppurative otitis media.
AB  - Chronic suppurative otitis media (CSOM) is defined as chronic otorrhea (i.e.,
      lasting > 6-12 weeks) through a perforated tympanic membrane. It is generally
      associated with some degree of conductive hearing loss. However, recurrent ear
      infections due to perforated eardrum result in absorption of toxins and
      macromolecules into the cochlea leading to sensorineural hearing loss (SNHL). We
      planned to determine the frequency of sensorineural hearing loss in chronic
      suppurative otitis media. A descriptive cross-sectional study was conducted at
      Aga Kgan University Hospital, Karachi, from October 2013 to March 2014. Average
      threshold of speech frequencies was calculated via pure tone audiogram for both
      diseased and normal contralateral ear.A mean of >25db in diseased ear was
      labelled as positive case for SNHL. SNHL was reported in 64(52%) patients and the
      frequency was found to increase with increasing duration. Patients with CSOM
      should be counselled regarding the risk of developing SNHL if left untreated.

PMID- 27895352
TI  - Effect of intra-abdominal pressure on post-laparoscopic cholecystectomy shoulder
      tip pain: A randomized control trial.
AB  - OBJECTIVE: To compare the effect of intra-abdominal pressure on postoperative
      shoulder-tip pain in laparoscopic cholecystectomy. METHODS: This was a randomized
      control study, conducted at Lady Reading Hospital Peshawar from January to August
      2013 on160 patients, randomized to two groups i.e. the low pressure (LPLC) and
      the standard pressure group (SPLC) where the intra abdominal pressures were kept
      10mmHg and above 10mmHg during surgery respectively. The age, gender, weight,
      duration of surgery, postoperative pain and frequency of analgesic administration
      in first 24 hours recorded and analyzed using Statistical Package for Social
      Sciences v20.0. Frequency and percentages were calculated for categorical while
      mean +/- SD was calculated for continuous variables. P-value of <0.05 was
      considered significant. RESULTS: The mean operative times in group A and B were
      27.84+/-6.078 vs. 28.51+/-7.45 minutes (p-value=0.625) respectively. Overall, the
      shoulder tip pain was reported in 25 (15%) patients. The frequencies in group A
      and B were 6 (7.5%) vs. 19 (23.8%) respectively (p-value = 0.005). The mean
      intensity of pain on VAS was 0.28+/-0.90 vs. 1.31+/-2.38 in the two groups
      respectively (p-value of 0.001). The mean number of analgesic administration in
      the first 24 hours was 2.24+/-0.48 in Group A vs.2.41+/-0.52 in Group B (p-value
      = 0.02) respectively. CONCLUSIONS: Our study shows that low intra-abdominal
      pressure results in reduced frequency of post-operative shoulder tip pain without
      any prolongation of duration of surgery.

PMID- 27895353
TI  - Bacterobilia in acute cholecystitis: Bile cultures' isolates, antibiotic
      sensitivities and antibiotic usage. A study on a Pakistani population.
AB  - Acute cholecystitis is one of the most common acute surgical conditions.
      Laparoscopic cholecystectomy remains the mainstay of treatment. In patients
      managed non-operatively, antibiotics play an important role in the treatment of
      cholecystitis. The current retrospective observational study was conducted at a
      tertiary care hospital in Karachi, and comprised medical records of patients
      admitted between 2008 and 2014with acute cholecystitis and in whom bile cultures
      were obtained. Of the 509 patients with a mean age of 51.15 +/- 13.4years, early
      laparoscopic cholecystectomy (within 72hours) was performed on 473(92.9%) cases,
      while the rest underwent percutaneous cholecystostomy. Bile cultureswere positive
      in 171(33.6%) patients. Predominantly gram-negative organisms were isolated among
      a total of 137(27%), with E.coli 63(46%) being the most commonly isolated
      organism. Of the gram-positive organism, enterococcus 11(8%) was the most common.
      Antibiotic sensitivities were determined.Based on our findings gram-negative
      coverage alone should be sufficient in our segment of the population.

PMID- 27895354
TI  - Nosocomial infections in the ICU: Pens and spectacles as fomites.
AB  - Nosocomial infections are a major cause of morbidity and mortality. Non-medical
      objects known as fomites may have a role in their genesis. We investigated the
      significance of writing pens and spectacles as fomites. The study was conducted
      at Aga Khan University Hospital, Karachi, from July 2013 to September 2013.
      Cultures were taken from pens and/or spectacles of resident nurses, doctors and
      nursing assistants in intensive care unit (ICU). Organisms important in ICU
      nosocomial infections were targeted. Seven rounds of sampling over 3 weeks led to
      55 pen and 5 spectacle samples. Growth was seen in 3(5.5%) pen samples and 1(20%)
      spectacle sample. Two (3.6%) pen cultures grew acinetobacter, 1)1.8%) grew
      candida and acinetobacter, and i spectacle culture grew vancomycin-resistant
      enterococcus faecium (VRE). Two out of the 4 (50%) personnel managing all ICU
      beds had growth. During the study, one or more ICU patients had infection with
      the same organisms. Pens and spectacles may be responsible for the spread of
      organisms like acinetobacter and VRE. Personnel managing multiple beds are more
      likely to carry contaminated fomites.

PMID- 27895355
TI  - Prediction of asialoglycoprotein receptors by correlated liver function
      parameters before hepatectomy.
AB  - Flow cytometric analysis of asialoglycoprotein receptor (ASGPR) levels on the
      surface of hepatocytes, which were obtained from the liver specimens of patients
      that received hepatectomy, were used as predictors of liver dysfunction after
      major hepatectomy for primary hepatocellular carcinoma (HCC) in Chinese patients,
      based on our previous study which confirmed the value of ASGPR levels on the
      surface of hepatocytes in evaluating the liver reserve function. The current
      study was planned to establish a conversion formula for the value of ASGPR with
      correlated liver function parameters. It was conducted from January 1, 2014, to
      June 30, 2015, at Beijing DiTan Hospital, Beijing, China, and comprised 55
      patients having undergone major hepatectomy. The outcomes of hepatectomy were
      compared with ASGPR levels and preoperative liver function parameters. A multiple
      linear regression model was used to identify the converted ASGPR value. The
      calculated ASGPR level was derived as: 80.695 + 0.002 * cholinesterases (CHE)
      (IU/L) - 0.620 * indocyanine green retention rate at 15 min (ICGR15)(%) - 0.655 *
      total bilirubin (TB) (umol/L). Receiver-operator characteristic curve analysis
      showed that the sensitivity and specificity of the ASGPR value <68.18% were 100%
      and 77.3% respectively for predicting liver dysfunction after hepatectomy. The
      converted ASGPR value may be reliable index for hepatic functional reserve in
      patients undergoing hepatectomy.

PMID- 27895356
TI  - The power peripherally inserted central catheter is superior to a central venous
      catheter in management of patients with esophageal variceal bleeding undergoing
      devascularization.
AB  - Peripherally-inserted central catheters (PICC) have a greater retention time and
      less complications compared to central venous catheters (CVC). The study was
      conducted from From January of 2014 to December 2015 at Beijing DiTan Hospital,
      Beijing, China, and comprised 70 patients undergoing devascularisation. Of the
      total, 36(51.4%) patients underwent placement of PICC (Group A), while 34(48.6%)
      underwent had CVC (Group B). Venous catheterisation was successful in all
      patients. The median duration of venous catheterization in Group A was greater
      than that in Group B (p=0.002). Catheter-associated complications did not differ
      between the groups (p=0.46). The level of blood platelet (PLT) count, Prothrombin
      activity (PTA) and white blood cell (WBC) count before venous catheterisation
      were independent risk factors for bleeding at the puncture site and catheter
      related infections. A Power PICC may be a better choice than a CVC in patients
      undergoing devascularisation requiring catheterisation. For patients with a lower
      PLT count, a decreased PTA, or a decreased WBC, venous catheterisation should be
      performed with caution.

PMID- 27895358
TI  - Paediatric traumatic brain injury: Presentation, prognostic indicators and
      Outcome analysis from a tertiary care center in a developing country.
AB  - Traumatic brain injury (TBI) is the leading cause of morbidity and mortality in
      children worldwide. This study was conducted to report the presentation,
      management, outcomes and prognostic indicators in a large series of patients from
      a tertiary care centre in a developing country. It is a review of prospectively
      collected data of paediatric patients with TBI admitted at our centre between
      July 2010 and December 2013. A total of 291 patients with a mean age of 7.2+/-5.0
      years were dichotomised into survivors and non-survivors, and variables were
      compared between the two groups. The mean post-resuscitation Glasgow coma scale
      (GCS) score was 11.6+/-3.9, mean Marshall Score was 2.26+/-0.95 and the mean
      revised trauma score at presentation was 10.58+/-1.7. Younger age, lower GCS
      score after resuscitation, lower revised trauma score, absent cisterns on
      imaging, associated subarachnoid haemorrhage (SAH) and intraventricular
      haemorrhage (IVH) and a lower Marshall score were associated with higher
      mortality.

PMID- 27895357
TI  - Better outcome of splenectomy in younger patients suffering from chronic immune
      thrombocytopenia (ITP).
AB  - Immune thrombocytopenia purpura (ITP) may need splenectomy after failure of
      medical treatment. The aim of this study was to explore the outcome of
      splenectomy in chronic ITP and to point out factors which can predict better
      response to splenectomy. This retrospective chart review was conducted at the Aga
      Khan University Hospital, Karachi, and comprised adult patients who underwent
      splenectomy for ITP from October 2005 to December 2015. Of the 51 patients,
      37(72.5%) were females and 14(27.5%) were males. The overall median age was 32
      years (interquartile range: 18-65 years). Complete response was seen in 43(84.3%)
      patients, 2(4%) had response and 6(11.7%) had no response. Relapse rate of ITP at
      1 year was 4(8.8%). Multivariate analysis showed that failure rate of splenectomy
      in the 41(80.4%) patients aged <50 years was 3(7%) as opposed to 3(30%) in the
      10(19.6%) patients aged >50 years (p=0.04). Splenectomy was found to be a safe
      and effective option for treatment of ITP. Young age at the time of surgery was
      associated with good response to surgery.

PMID- 27895359
TI  - Awake craniotomy for brain tumours in Pakistan: An initial case series from a
      developing country.
AB  - Awake craniotomy offers safe resection of brain tumours in eloquent area. Aga
      Khan University Hospital, Karachi, recently started the programme in Pakistan,
      and the current study was planned to assess our experience of the first 16
      procedures. The retrospective study comprised all such procedures done from
      November 2015 to May 2016. Pre-operative and post-operative variables were
      analysed. Of the 16 patients, 11(68.75%) were males and 5(31.25%) were females.
      The overall median age was 37 years (interquartile range[IQR]: 23-62 years). The
      most common presenting complaint was seizures 8(50%), followed by headache6(38%).
      The common pathologies operated include oligodendroglioma and glioblastoma. Pre
      operative mean Karnofsky Performance Status score was 76+/-10, which increased to
      96+/-7 post-operatively at discharge. Besides, 2(12.5%) intra-operative
      complications were observed, i.e. seizure and brain oedema, in the series. The
      study had median operative time of 176 minutes (IQR: 115-352) and median length
      of stay of 4 days (IQR: 3-7).Awake craniotomy was highly effective in maintaining
      post-operative functionality of the patient following glioma resection. It was
      also associated with shorter hospital course and so lower cost of management.

PMID- 27895360
TI  - Paediatric External Ventricular Drains: Experience from a tertiary care hospital
      of a Developing Country.
AB  - The aim of the study was to describe indications and complications of external
      ventricular drain (EVD) placement in children aged between 1 month and 16 years.
      This retrospective chart review was conducted at the Aga Khan University
      Hospital, Karachi, and comprised all children who underwent EVD placement from
      January 2007 to December 2014. Of the 177 patients identified, 117(66%) were
      males 60(34%) were girls. The overall mean age was 5.4+/-5.2 years. The median
      Glasgow Coma Scale score on presentation and discharge was 13 (interquartile
      range [IQR]: 7) and 15 (IQR: 4), respectively. Major diagnosis included
      intracranial tumour 60(34%), bacterial meningitis 34(19%), tuberculous meningitis
      33(18.6%), and haemorrhage 23(13%). Clinical indications for EVD insertion were
      acute hydrocephalus secondary to infection 64(36.2%), tumour 54(30.5%), and
      haemorrhage 23(13%) ventriculoperitoneal shunt malfunction or infection 25(14.1%)
      and traumatic brain injury 11(6.2%). Complications were observed in 47(26%)
      patients including infections 25(14.1%), malfunction 11(6.2%), haemorrhage
      6(3.4%), misplacement 3(1.7%) and obstruction 2(1.1%). Staphylococcus was the
      main organism isolated. Moreover, 25(14%) patients expired. Acute hydrocephalus
      was the major indication and EVD infection was the major complication.

PMID- 27895361
TI  - Neurosurgery training in Pakistan: Follow-up survey and critical analysis of
      National Training Programmes.
AB  - This cross-sectional nation-wide survey was planned to assess the current status
      of neurosurgery residency training in Pakistan and to compare it with the results
      of a previous study. The duration of study was from July to December 2015. It
      comprised of neurosurgery trainees enrolled with the College of Physicians and
      Surgeons of Pakistan (CPSP). In this study, 43 trainees from 13 centres were
      included. The mean duration of training acquired by participants was 2.8+/-1.9
      years. The mean work hours were 73.8+/-21.9 per week. Moreover, 28(65%) trainees
      had access to at least one neurosurgery journal while 29(67%) did not have any
      indexed publication. Besides, 2(15.4%) centres did not have internet facility and
      more than half did not have a regular morbidity and mortality meeting. Training
      facilities were highly variable in different institutes. When compared with
      previous study, little improvement occurred during the previous six years. We
      recommend a uniform academic curriculum and standardisation of training
      facilities among different institutes.

PMID- 27895362
TI  - A review of scleral buckle procedures performed at a tertiary care center in
      Karachi, Pakistan.
AB  - This retrospective study was done to evaluate the visual and anatomic outcomes of
      scleral buckling for the repair of rhegmatogenous retinal detachment (RRD). All
      scleral buckle procedures performed at the Aga Khan University Hospital, Karachi,
      from May 1999 to April 2012 were included. A total of 75 eyes of 72 patients were
      studied. The mean age of patients at surgery was 33.0+/-17.2 years. The mean
      logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was
      0.9+/-0.8 pre-operatively and 0.5+/-0.6 at 1 year (p=0.018). At baseline, 27(36%)
      eyes had a best corrected visual acuity (BCVA) of 20/50 or better, while at 1
      year after surgery 47(63.5%) eyes had BCVA of 20/50 or better. Retina had
      successfully attached after first attempt in 70(93.3%) cases. Scleral buckling
      for the repair of RRD resulted in a high anatomical success rate as well as
      significant improvement in visual acuity.

PMID- 27895363
TI  - A systematic review of epidemiological literature on the eye health of
      marginalized fishing populations.
AB  - A systematic review was conducted in December 2013 to examine the extent to which
      health research has been focused on the eye health issues of fishing communities.
      We searched multiple databases to identify relevant citations, using a
      combination of Medical Subject Headings (MeSH) and text words representing eye
      health, fishing populations and measures of disease frequency. The search yielded
      only 4 studies, described in 5 articles. Three studies (one each in Turkey, Egypt
      and Spain) provided data on self-reported eye problems in fishermen or fishery
      workers, with prevalence ranging from 38% to 81%. There was only one study in the
      literature that objectively assessed the burden and causes of vision impairment
      and blindness in fishing communities. None of the studies examined availability,
      accessibility, acceptability and quality of eye care services. We conclude that
      marginalized fishing communities are almost non-existent in eye health
      literature. Eye health needs of these and other marginalized populations must be
      identified and addressed in post-2015 health and development agenda.

PMID- 27895364
TI  - A 10-year review of indications for penetrating keratoplasty in a tertiary care
      setting in Karachi Pakistan.
AB  - The retrospective study was conducted to determine the indications and outomes of
      penetrating keratoplasty(PKP) in a tertiary care setting in Pakistan. All eyes
      that had undergone PKP between January 2005 and December 2014 at the Aga Khan
      University Hospital, Karachi, were included.Data were collected on the
      indications of PKP, graft survival (graft clarity at final follow-up), andbest
      corrected visual acuity (BCVA).Kaplan-Meier?'s method was usedto analyse graft
      survival.Out of 437 eyes, 383(87%) were for visual purpose. Trauma-related
      corneal scarring 113(26.2%) was the leading cause of PKP, followed by keratoconus
      74(17.1%), redo graft 56(13%), infection-related corneal opacity 46(10.6%),
      corneal dystrophy 44(10.2%) and bullous keratopathy 36(8.3%). The probability of
      graft survival at 30 months was 90% for keratoconusversus 75% for the non
      keratoconus grafts. Most of the PKPs in this case series were due to preventable
      causes. Our long-term PKP results were favourable, with a graft survival
      ratecomparable to those of other centres.

PMID- 27895365
TI  - Indications of enucleations and eviscerations performed at a tertiary eye care
      unit: A case series.
AB  - The retrospective study was planned to look at the indications of eye
      enucleations and eviscerations, and comprised all such procedures done at the Aga
      Khan University Hospital, Karachi, from January 2006 to December 2015. Data was
      collected regarding age at the time of procedure, gender, procedure type,
      indication for enucleation or evisceration, type of implant if used and
      complications. Of the 66 eyes of 65 individuals, 47 (71.2%) underwent
      evisceration and 19 (28.8%) enucleation. The mean age at the time of the
      procedures was 37.86+/-23.09 years. The indication for enucleation or
      evisceration were keratitis 14(21.2%), introcular tumours 13(19.7%), trauma
      10(15.2%), endophthalmitis 10(15.2%), cosmesis 10(15.2%) and painful blind eye
      9(13.6%). Only 5(7.5%) procedures had postoperative complications such as wound
      dehiscence, infected socket, loose suture, or stich abscess. Most of causes of
      enucleation and evisceration in this case series could have prevented through the
      application of evidence-based safety practices.

PMID- 27895366
TI  - Intra-operative implantation errors during Austin Moore Hemiarthroplasty.
AB  - Austin Moore hemiarthroplasty is an established treatment in elderly patients
      with neck of femur fractures. Being commonly performed, it is also associated
      with several technical errors of implantation which results in complications and
      failure requiring revision surgery. This retrospective pre- and post-operative
      radiographic study to determine the frequency of technical errors was conducted
      at the Indus Hospital, Karachi, and comprised data of 50 patients who underwent
      Austin Moore hemiarthroplasty between January and November 2016. Of the total,
      29(58%%) patients had no error of implantation. Overhanging of prosthesis was
      observed in 21(42%) patients, followed by inadequate length of the neck remnant
      in 18(36%). Moreover, 8(16%) patients sustained intra-operative periprosthetic
      fractures managed with cerclage wire. Also, 33(66%) patients had a Dorr type
      Afemur morphologic pattern. Hemiarthroplasty was found to be a technically
      demanding procedure associated with avoidable intra-operative implantation errors
      by proper preoperative planning, careful patient selection, proper training of
      surgeons, hence avoiding failure.

PMID- 27895367
TI  - Two incision mini open carpal tunnel release- a minimally invasive alternative to
      endoscopic release.
AB  - Surgical techniques for carpal tunnel release are constantly evolving to reduce
      complications. This retrospective study was planned to identify the outcome and
      complications associated with a new operating technique for release of carpal
      tunnel using two incisions. It was conducted at the Aga Khan University Hospital,
      Karachi, and comprised patients undergoing surgical release of carpal tunnel
      syndrome (CTS) between January 2011 and December 2014. Of the 54
      patients,38(70.4%) cases were of right-sided CTS. The mean operating time was
      12.5+/-4.9 minutes. Complete relief from symptoms was observed in all the
      patients and the only complication noted was superficial infection in 2(3.7%)
      patients.The outcomes and complications associated with this technique were
      comparable with other standard techniques. No major complication (e.g.
      neurovascular injury) was reported, which showed that this technique was safe and
      had no additional risks. Therefore, it can be used as an alternative to
      endoscopic release which is expensive and requires special training and
      equipment.

PMID- 27895368
TI  - Does obesity affects early infection after total knee arthroplasty. A comparison
      of obese vs non obese patients.
AB  - Surgical site infection (SSI) is a disastrous complication after total knee
      arthroplasty (TKA) which can cause prosthesis loosening and may end up in
      septicaemia. The incidence of infection reported to be in the range of 0.3-12.4%
      for primary TKA. Significantly higher infection rate is found in the morbidly
      obese patients. The current study compared the immediate rate of post-total knee
      replacement wound infection in the obese versus non-obese population. The cross
      sectional study was conducted at Aga Khan University Hospital (AKUH) and
      comprised patients undergoing TKA for primary knee osteoarthritis. Surgical
      outcome was measured by the Southampton wound infection score at 1-month follow
      up. Out of 142 enrolled patients with a mean age of 67.8+/-56 years, infection
      was confirmed in 3(2.11%) patients who needed surgical management. All the
      patients who developed SSIs were females.

PMID- 27895369
TI  - Improvement in quality of lifesix months after primary total hip arthroplasty in
      a Pakistani population.
AB  - This prospective, cohort study was carried out to assess the improvement in
      quality of life of patients undergoing elective primary total hip arthroplasty
      (THA). It was conducted at the orthopaedic department of the Aga Khan University
      Hospital, Karachi, from June 2014 to May 2015, and comprised patients who had
      undergone THA. A total of 89 patients having a mean age of 41.5+/-12.0 years with
      a baseline core outcomes measure index (COMI)-hip score of > 3.5 were included. A
      decrease in COMI-hip score by >3 points six months post-operatively was
      considered improvement in quality of life. Patient satisfaction with restriction
      to squatting was assessed separately. The mean reduction in COMI-hip was 4.9+/
      1.3 with 83(93%) patients experiencing significant improvement in quality of
      life. Age >50 years and American Society of Anaesthesiologists (ASA) level >III
      was significantly associated with no improvement in quality of life. Most
      patients were satisfied with their disability to squat irrespective of COMI-hip
      score. THA was found to be associated with significant improvement in quality of
      life and COMI-hip score was applicable in our population despite its inability to
      assess disability with restriction in squatting.

PMID- 27895370
TI  - Lower red cell transfusion rates with use of tranexamic acid in single-stage
      bilateral total knee arthroplasty: A retrospective audit.
AB  - Bilateral total knee arthroplasty (BTKA) patients may require blood transfusion
      which has its risks. Anti-fibrinolytic drugs such as aprotinin, aminocaproic acid
      and tranexamic acid (TXA) have reduced transfusion requirements in major surgery.
      This retrospective audit was performed to assess effectiveness of TXA in reducing
      blood transfusion rate in single-stage sequential BTKA cases operated by a single
      surgeon. Records of 91 patients given TXA and 80 controls who were operated
      before 2012 and not given TXA were reviewed. TXA was given 15mg/kg intravenously
      (IV) before tourniquet deflation and 3 hours postoperatively.Blood transfusion
      was done in 9(10%) patients in the TXA group compared to 20(25%)in the control
      group (p<0.01). One (1.25%) patient in the control group had non-fatal pulmonary
      embolism.TXA appeared to be effective in decreasing post-operative blood loss and
      requirement for blood transfusion after single-stage BTKA.

PMID- 27895372
TI  - Diagnostic value of sinus tract culture versus intraoperative bone culture in
      patients with chronic osteomyelitis.
AB  - To compare the organisms isolated from the sinus tract culture and intraoperative
      bone culture in patients with chronic osteomyelitis. This cross sectional
      prospective study was conducted from February 2015 to March 2016. Ninety
      consecutive patients were enrolled in study (n=90). Inclusion criteria were
      patients with either sex, any age, chronic osteomyelitis having discharging
      sinus. Sample from sinus tracts and bone were taken through standardized aseptic
      technique and organism were cultured. There were 62 males and 28 females, male to
      female ratio 3:1, mean age was 40 years. 23 patients had primary osteomyelitis
      and 67 had secondary osteomyelitis. 68 patients had orthopaedic implant
      infections. In 61/90 (67%) patients the same organism was isolated on both sinus
      tract and intraoperative cultures.In our scenario we found that within the
      limitations of this study, there was a high ratio of agreement between the sinus
      tract and intraoperative cultures. We conclude that if used judiciously, sinus
      tract cultures can yield accurate results in the majority of cases.

PMID- 27895371
TI  - Rotational Mal-Alignment after Reamed Intramedullary Nailing for tibial shaft
      fracture.
AB  - Intra-medullary (IM) nailing is standard of care for unstable tibial shaft
      fractures. Malrotation is very common but it is under-recognised, inpart because
      of variation in normal anatomy and partly due to difficulty in accurately
      assessing rotation. This study was planned to evaluate the frequency of
      rotational mal-alignment after reamed tibia IMnailing. This cross-sectional study
      was conducted at Aga khan University Hospital, Karachi, and comprised patients
      with tibia shaft fractures managed with IMnailing from January to December 2014.
      All the patients were assessed intra-operatively for rotational alignment using
      the knee and ankle fluoroscopic images. There were 81 patients with a mean age of
      38+/-16.9 years. There were 64(79%) male patients. Overall the incidence of
      malrotation was in 20(24.7%) cases. Rotational mal-alignment is one of the
      preventable complications after IMnailing which can be assesed intra-operatively
      under fluoroscope.

PMID- 27895373
TI  - Percutaneous Ilio-sacral Screw Fixation for Unstable Pelvic Ring Injuries.
AB  - This prospective interventional study was planned to determine the clinical and
      radiological outcome of percutaneous iliosacral screw fixation for unstable
      pelvic ring injuries. It was conducted from March 2008 to June 2014 at the
      Department of Orthopaedic Surgery Combined Military Hospital (CMH) at Lahore,
      Multan, Rawalpindi and Muzaffarabad. It comprised 50 patients with unstable
      pelvic ring injuries. Visual analogue scale (VAS), Majeed pelvic score and
      Lindahl criteria were used for functional and radiological outcomes assessment.
      The mean age of the patients was 47.82+/-8.94 years. Moreover, 33(66%)
      participants were males and 17(34%) were females. The mean pre-operative Majeed
      and VAS scores were 38.98+/-6.28 and 9.04+/-0.67, respectively. Operating time
      and blood loss were reduced significantly. VAS score for post-operative pain was
      3.82+/-1.26 at 1 month and decreased further to 2.68+/-1.30 at 12 months post
      operatively (p<0.001). Radiological outcome and the post-operative Majeed scores
      were good to excellent in 43(86%) cases. Thus Percutaneous iliosacral screw
      fixation of unstable pelvic ring injuries resulted in excellent radiological and
      functional outcome with significantly decreased post-operative VAS score for SI
      joint pain.

PMID- 27895374
TI  - Pediatric laparoscopic surgery; initial experience from Pakistan; first 100 cases
      in single center.
AB  - In a developing country like Pakistan, laparoscopic surgeries are not considered
      favourable by many, possibly because of high costs or a lack of expertise. It is
      an established fact that laparoscopic surgery offers better surgical treatments
      with a shorter hospital stay and fewer complications. The current retrospective
      study was conducted at a tertiary care hospital in Karachi and comprised of
      laparoscopy cases performed by a single surgeon from March 2012 to September of
      2014. A total of 100laparoscopic surgeries were performed; mostly appendectomies
      49(49%) and undescended testes (UDTs) 34(34%). Overall, there were 70(70%) male
      patients. The mean age of the patients was 7.1 years and standard deviation (SD)
      of 2. Four (4%) patients had cellulitis. Laparoscopy paediatric surgery offered
      advantages of fewer wound-associated complications, less incisional pain, a
      shorter recovery time, and improved cosmesis.

PMID- 27895375
TI  - Clinical profile, treatment and survival outcomes of peadiatric germ cell
      tumours: A Pakistani perspective.
AB  - Germ Cell Tumours (GCTs) are rare tumours. Generally 80% are benign and 20%
      malignant with a bimodal age distribution. The retrospective study was conducted
      at Shaukat Khanum Cancer Hospital, Lahore, Pakistan, and comprised all paediatric
      patients below 18 years of age who received treatment for histology-proven GCT
      from 2006 to 2014. Of the 207 patients, 98(42.3%) were males and 109(52.7%) were
      females. The most common GCT was yolk sac tumour in 90(43.5%) children followed
      by mixed GCT in 40(19.3%) and dysgerminoma in 34(16.4%). Gonads were most
      commonly involved in 165(79.7%) patients with metastasis in 24(11.6%) at
      presentation and recurrence in 26(12.5%) patients. Overall, 133(64.3%) patients
      are well and followed up at regular intervals and 55(26.5%) have been lost to
      follow-up with an expected overall 5-year median survival of 45%. Despite the
      distinct clinical profile of paediatric GCT, survival can be improved by early
      diagnosis, regimented treatment according to set guidelines, protocols and by
      improving follow-up.

PMID- 27895376
TI  - Versatility of the Anterolateral Thigh Flap: An AKUH experience.
AB  - Anterolateral thigh flap is used for reconstruction of various soft tissue
      defects. We planned the study to evaluate the versatility of the anterolateral
      thigh flap as it may be used for reconstruction of head and neck, torso and
      extremities with minimal donor-site morbidity. The retrospective study was
      conducted at Aga Khan University Hospital, Karachi, and comprised date from
      October 2012 to December 2015. Of the 75 patients in which anterolateral thigh
      flap was used for reconstruction, 6(8%) flaps did not survive. The overall flap
      survival was 69(92%). Anterolateral thigh flap was versatile enough to provide
      soft tissue coverage to defects of various soft tissue and bulk requirements.
      Adequate outcomes were achieved pertaining to the reconstruction of the soft
      tissue defects. Anterolateral thigh flap can be used to reconstruct soft tissue
      defects almost anywhere and almost of any complexity.

PMID- 27895377
TI  - Frequency and predictors of recurrence of bladder tumour on first check
      cystoscopy - a tertiary care hospital experience.
AB  - OBJECTIVE: To determine the frequency and predictors of non-muscle invasive
      bladder tumour recurrence on first-check cystoscopy after transurethral resection
      of bladder tumour. METHODS: This cross-sectional study was conducted at the Aga
      Khan University Hospital, Karachi, from April to November 2014, and comprised
      patients with a suspected newly-diagnosed urothelial cancer. Patients with non
      muscle invasive disease with complete resection of all visible lesions along with
      deep biopsy from the tumour base were included. Patients received standard
      adjuvant intravesical therapy according to their risk stratification and
      underwent a white-light check cystoscopy at 3 months to look for tumour
      recurrence. Association between clinico-pathological variables and recurrence at
      first cystoscopy was determined. SPSS 20 was used for data analysis. RESULTS: The
      mean age of 84 patients at presentation was 63.3+/-12.5 years (range: 36-89
      years). There were 75(89%) men and 9(11%) women. On initial transurethral
      resection, the size of tumour was less than 3cm in 32(38%) participants and equal
      to or above 3cm in 52(62%). Single tumour was found in 51(61%) subjects and
      multiple tumours in 33(39%). None of the resected tumours was primary carcinoma
      in situ and 35(42%) tumours were of high grade. The overall recurrence rate at
      first cystoscopy was 28(33.3%). Larger tumour, higher grade and tumour
      multifocality were factors associated with recurrence at check cystoscopy (p<0.05
      each). Patients?' age, gender, smoking status and tumour stage did not correlate
      with early recurrence (p>0.05 each). CONCLUSIONS: The number, size and grade of
      the tumour strongly correlated with recurrence at check cystoscopy.

PMID- 27895378
TI  - Intravesical Foreign Body: Tertiary care center experience from Pakistan.
AB  - Foreign body in bladder is relatively uncommon condition with variable
      presentations. Literature is limited to case reports and small series from
      region. Therefore, we planned this study to review our experience regarding
      intravesical foreign body. This retrospective study was conducted at the Aga Khan
      University Hospital, Karachi, and comprised 14 patients having intravesical
      foreign bodies from March 1989 to March 2013. Demographics, presentation, mode of
      insertion, type of foreign body and management were noted. Of the 11(78.6%)
      patients included in the study, 10(90.9%) patients were male and 1(9.1%) was
      female. The mean age was 51+/- 20 years. In 5(45.5%) patients, foreign bodies
      reached bladder by iatrogenic route followed by self-insertion in 4(36.4%)
      patients. Retrieved foreign bodes included piece of Foley?'s catheter, electric
      wire, ureteric stent, plastic material, double-J stent pusher, Endo
      gastrointestinal (GI) staples, sticks of broom and bomb shrapnel. All patients
      were managed successfully with endoscopic removal. However, 5(45.5%) patients
      required additional urological procedures. This could represent a urologic
      challenge. Careful history and symptoms could lead to further investigations.

PMID- 27895379
TI  - Functional outcomes after successful lower extremity arterial injuries repair.
AB  - The study was conducted to measure functional outcome of patients who had
      successful lower extremity arterial reconstruction after vascular injury at a
      tertiary care centre in Karachi over 5 years from January 2008 to December 2013.
      In this descriptive cohort study, the functional outcomes were assessed with
      lower extremity functional scale (LEFS). The mean age the 75 patients in the
      study was 32+/-11 years. Limb salvage was successful in 72(96%) cases. The most
      common injured artery was superficial femoral artery 30(40%) followed by
      popliteal artery 19(25%). The most common method of repair was end-to-end using
      either polytetrafluoroethylene (PTFE) graft 43(57%) or vein interposition
      grafting 19(25%). Two (2.66%) patients with delayed presentation had secondary
      amputation. One (1.33%) patient had graft infection. Acceptable good functional
      outcome was noted with a mean LEFS of 72+/-8.

PMID- 27895380
TI  - The Age-Related Macular Degeneration Complex: Linking Epidemiology and
      Histopathology Using the Minnesota Grading System (The Inaugural Frederick C.
      Blodi Lecture).
AB  - PURPOSE: To describe the histopathologic findings of the four stages of age
      related macular degeneration (AMD) as defined by the Age-Related Eye Disease
      Study (AREDS) using the Minnesota grading system (MGS). CLINICAL RELEVANCE: There
      are no animal models for AMD. Eye banks enable access to human tissue with AMD.
      The level of AMD (grades 1 through 4) as defined by AREDS is determined ex vivo
      using the MGS. The AREDS has the largest collection to date of prospectively
      gathered data on the natural history of AMD. Since the MGS uses the same clinical
      criteria as AREDS, the addition of histopathologic findings of graded tissue
      confirms important pathophysiology at each stage of AMD. METHODS: Four eye bank
      eyes were graded according to the MGS. Only the right eyes were dissected for
      phenotype grading. The fellow (left) eyes were fixed for histopathologic study.
      The eyes were serially sectioned (7 MUm) through the macula. Individual slides
      were examined, and a two-dimensional reconstruction of the topography of the
      macula was created for each donor. Selected, unstained slides were used for
      immunohistochemical staining. In one donor, portions of tissue were obtained for
      transmission electron microscopic (TEM) processing. RESULTS: Donor 1 had a rare
      hard, nodular druse (MGS1). Donor 2 had intermediate confluent drusen (MGS2).
      Donor 3 had numerous intermediate drusen (MGS3) in the right eye. Histopathology
      of the fellow left showed basal laminar deposits (BLamD), soft drusen, and an
      area of occult choroidal neovascularization underlying the retinal pigment
      epithelium (RPE) with endothelial cells (CD31-positive). Donor 4 also had MGS 3
      along with reticular pseudodrusen (RPD). Histologic and TEM examination
      demonstrated diffuse BLamD, thickening of Bruch's membrane, hard drusen, and
      focal nodules underlying the RPE that corresponded to the RPD. EM examination
      demonstrated both BLamD and electron-dense material located just external to the
      elastic layer of Bruch's membrane. CONCLUSION: Eye bank eyes graded using the MGS
      serve as an important link to the phenotypic and epidemiologic data from the
      AREDS. Thus, the MGS serves as a system to study the histopathology at each stage
      of AMD to better understand the relevant pathophysiologic changes in disease
      progression.

PMID- 27895381
TI  - Reactive oxygen species induce neurite degeneration before induction of cell
      death.
AB  - Reactive oxygen species (ROS) induce neuronal cell death in a time- and
      concentration-dependent manner. Treatment of cultured cells with a low
      concentration of hydrogen peroxide induces neurite degeneration, but not cell
      death. Neurites (axons and dendrites) are vulnerable to ROS. Neurite degeneration
      (shrinkage, accumulation, and fragmentation) has been found in neurodegenerative
      disorders, such as Alzheimer's disease, Parkinson's disease, and Huntington's
      disease. However, the mechanism of ROS-related neurite degeneration is not fully
      understood. Many studies have demonstrated the relationship between mitochondrial
      dysfunction and microtubule destabilization. These dysfunctions are deeply
      related to changes in calcium homeostasis and ROS production in neurites.
      Treatment with antioxidant substances, such as vitamin E, prevents neurite
      degeneration in cultured cells. This review describes the possibility that ROS
      induces neurite degeneration before the induction of cell death.

PMID- 27895382
TI  - Non-invasive measurement of melanin-derived radicals in living mouse tail using X
      band EPR.
AB  - The aim of this experiment is to measure in vivo generation of melanin-derived
      radicals non-invasively, as a quantifiable index of radio-biological effect.
      Melanin-derived radicals in a living intact mouse tail tip were non-invasively
      measured in very simple way using an X-band electron paramagnetic resonance
      spectrometer. Colored mouse strains, C57BL/6NCr, BDF1, and C3H/He, have clear EPR
      signal corresponding to melanin-derived radicals in the tail tip; however, albino
      mouse strains, BALB/cCr, ddY, ICR, have no EPR signals. An X-ray fraction of 2
      Gy/day (1 Gy/min) was repeatedly irradiated to a C3H/He mouse tail skin every
      Monday to Friday for 4 weeks. In comparison to before starting irradiation, the
      C3H/He mouse tail skin became darker, like a suntan. The melanin-derived radicals
      in C3H/He mouse tail skin were increased in association with X-ray fractions.
      Melanin-derived radicals in mouse tail skin can be readily and chronologically
      measurable by using X-band EPR spectrometer, and can be a marker for a
      radiobiological effect in the skin.

PMID- 27895383
TI  - Preparation and antioxidant/pro-oxidant activities of 3-monosubstituted 5
      hydroxyoxindole derivatives.
AB  - Antioxidant treatments have been expected to be a novel therapeutics for various
      oxidative stress-mediated disorders. Our previous study revealed that 5
      hydroxyoxindole and its 3-phenacyl-3-hydroxy derivatives showed excellent
      antioxidant activities such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
      scavenging activity and lipid-peroxidation inhibitory activity. However, the DPPH
      radical scavenging activity of the 3,3-disubstituted derivatives was lower than
      that of the original 5-hydroxyoxindole. In the present study, we synthesized
      novel 3-monosubstituted 5-hydroxyoxindole derivatives that exhibited stronger
      DPPH radical scavenging activities and lipid peroxidation-inhibitory activities
      than the 3,3-disubstituted 5-hydroxyoxindoles. Moreover, the 3-monosubstituted 5
      hydroxyoxindole derivatives showed neither an iron-mediated pro-oxidant effect
      nor a remarkable cytotoxicity against HL-60 cell lines except some of the highly
      lipophilic compounds. These results indicate that 3-monosubstituted 5
      hydroxyoxindoles can be used as a promising antioxidant scaffold for drug
      discovery.

PMID- 27895384
TI  - Exendin-4 induces extracellular-superoxide dismutase through histone H3
      acetylation in human retinal endothelial cells.
AB  - Extracellular-superoxide dismutase (genetic name SOD3) is a secreted anti
      oxidative enzyme, and its presence in vascular walls may play an important role
      in protecting the vascular system against oxidative stress. Oxidative stress has
      been implicated in the pathogenesis of diabetic retinopathy; therefore, increases
      in extracellular-superoxide dismutase have been suggested to inhibit the
      progression of diabetic retinopathy. Incretin-based drugs such as glucagon-like
      peptide-1 receptor agonists are used in the treatment of type 2 diabetes.
      Glucagon-like peptide-1 receptor agonists are expected to function as
      extrapancreatic agents because the glucagon-like peptide-1 receptor is expressed
      not only in pancreatic tissues, but also in many other tissue types. We herein
      demonstrated that exendin-4, a glucagon-like peptide-1 receptor agonist, induced
      the expression of extracellular-superoxide dismutase in human retinal
      microvascular endothelial cells through epigenetic regulation. The results of the
      present study demonstrated that exendin-4 induced the expression of extracellular
      superoxide dismutase through histone H3 acetylation at the SOD3 proximal promoter
      region. Moreover, plasma extracellular-superoxide dismutase concentrations in
      diabetic patients were elevated by incretin-based therapies. Therefore, incretin
      based therapies may exert direct extrapancreatic effects in order to protect
      blood vessels by enhancing anti-oxidative activity.

PMID- 27895385
TI  - Involvement of reactive oxygen species derived from mitochondria in neuronal
      injury elicited by methylmercury.
AB  - Methylmercury induces oxidative stress and subsequent neuronal injury. However,
      the mechanism by which methylmercury elicits reactive oxygen species (ROS)
      production remains under debate. In this study, we investigated the involvement
      of mitochondrial ROS in methylmercury-induced neuronal cell injury using human
      neuroblastoma SH-SY5Y-derived rho0 cells, which have a deletion of mitochondrial
      DNA and thus decreased respiratory activity. SH-SY5Y cells were cultured for 60
      days in the presence of ethidium bromide to produce rho0 cells. Our rho0 cells
      showed decreases in the cytochrome c oxidase expression and activity as well as
      oxygen consumption compared with original SH-SY5Y cells. Methylmercury at a
      concentration of 1 uM induced cell death with oxidative stress in original SH
      SY5Y cells, but not rho0 cells, indicating that rho0 cells are resistant to
      methylmercury-induced oxidative stress. rho0 cells also showed tolerance against
      hydrogen peroxide and superoxide anion, suggesting that rho0 cells are resistant
      to total ROS. These data indicate that mitochondrial ROS are clearly involved in
      oxidative stress and subsequent cell death induced by methylmercury. Considering
      that the dominant mechanism of ROS generation elicited by methylmercury is due to
      direct antioxidant enzyme inhibition, mitochondria might play a role in
      amplifying ROS in methylmercury-induced neurotoxicity.

PMID- 27895386
TI  - Addition of strawberries to the usual diet increases postprandial but not fasting
      non-urate plasma antioxidant activity in healthy subjects.
AB  - Strawberries can augment plasma antioxidant activity, but this may be confounded
      by selection of methods, time of blood sampling and concomitant dietary
      restrictions. We examined the effect of strawberry consumption on ferric reducing
      ability (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging
      activity (DPPH-test) of native and non-urate plasma in healthy subjects on their
      usual diet. Eleven subjects consumed strawberries (500 g daily) for 9 days.
      Fasting and 3-h postprandial plasma and 24-h urine collection were obtained
      before, during and after strawberry course for FRAP, DPPH-test and polyphenols
      determination. Fifteen subjects served as a control in respect to plasma
      antioxidant activity changes and effect of 300 mg of oral ascorbate. First, 5th
      and 9th strawberry dose increased 3-h postprandial DPPH-test by 17.4, 17.6 and
      12.6%, and FRAP by 15.5, 25.6 and 21.4% in comparison to fasting values in non
      urate plasma (p<0.05). In native plasma only a trend was observed to higher
      postprandial values for both tests. Strawberries increased urinary urolithin A
      and 4-hydroxyhippuric acid whereas plasma polyphenols were stable. No changes of
      FRAP and DPPH-test were noted in controls and after ascorbate intake.
      Strawberries transiently increased non-urate plasma antioxidant activity but this
      cannot be attributed to direct antioxidant effect of polyphenols and ascorbate.

PMID- 27895387
TI  - Retention of acetylcarnitine in chronic kidney disease causes insulin resistance
      in skeletal muscle.
AB  - Insulin resistance occurs frequently in patients with chronic kidney disease.
      However, the mechanisms of insulin resistance associated with chronic kidney
      disease are unclear. It is known that an increase in the mitochondrial acetyl-CoA
      (AcCoA)/CoA ratio causes insulin resistance in skeletal muscle, and this ratio is
      regulated by carnitine acetyltransferase that exchanges acetyl moiety between CoA
      and carnitine. Because excess acetyl moiety of AcCoA is excreted in urine as
      acetylcarnitine, we hypothesized that retention of acetylcarnitine might be a
      cause of insulin resistance in chronic kidney disease patients. Serum
      acetylcarnitine concentrations were measured in chronic kidney disease patients,
      and were significantly increased with reduction of renal function. The effects of
      excess extracellular acetylcarnitine on insulin resistance were studied in
      cultured skeletal muscle cells (C2C12 and human myotubes), and insulin-dependent
      glucose uptake was significantly and dose-dependently inhibited by addition of
      acetylcarnitine. The added acetylcarnitine was converted to carnitine via reverse
      carnitine acetyltransferase reaction, and thus the AcCoA concentration and
      AcCoA/CoA ratio in mitochondria were significantly elevated. The results suggest
      that increased serum acetylcarnitine in CKD patients causes AcCoA accumulation in
      mitochondria by stimulating reverse carnitine acetyltransferase reaction, which
      leads to insulin resistance in skeletal muscle.

PMID- 27895388
TI  - Acetate alters expression of genes involved in beige adipogenesis in 3T3-L1 cells
      and obese KK-Ay mice.
AB  - The induction of beige adipogenesis within white adipose tissue, known as
      "browning", has received attention as a novel potential anti-obesity strategy.
      The expression of some characteristic genes including PR domain containing 16 is
      induced during the browning process. Although acetate has been reported to
      suppress weight gain in both rodents and humans, its potential effects on beige
      adipogenesis in white adipose tissue have not been fully characterized. We
      examined the effects of acetate treatment on 3T3-L1 cells and in obese diabetic
      KK-Ay mice. The mRNA expression levels of genes involved in beige adipocyte
      differentiation and genes selectively expressed in beige adipocytes were
      significantly elevated in both 3T3-L1 cells incubated with 1.0 mM acetate and the
      visceral white adipose tissue from mice treated with 0.6% acetate for 16 weeks.
      In KK-Ay mice, acetate reduced the food efficiency ratio and increased the whole
      body oxygen consumption rate. Additionally, reduction of adipocyte size and
      uncoupling protein 1-positive adipocytes and interstitial areas with multilocular
      adipocytes appeared in the visceral white adipose tissue of acetate-treated mice,
      suggesting that acetate induced initial changes of "browning". In conclusion,
      acetate alters the expression of genes involved in beige adipogenesis and might
      represent a potential therapeutic agent to combat obesity.

PMID- 27895389
TI  - Comparisons of dietary intake in Japanese with non-alcoholic fatty liver disease
      and type 2 diabetes mellitus.
AB  - Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease that
      involves a complex interaction between genetics, diet, and lifestyle, all of
      which combine to form the NAFLD phenotype. In Japan, medical nutrition therapy
      for NAFLD has not yet been established, so NAFLD patients are instructed in the
      dietary modifications used for type 2 diabetes mellitus (T2DM). Because points of
      difference may exist in the effects of dietary choices on NAFLD and T2DM, the
      present study aimed to compare and assess the dietary intake of Japanese
      individuals with NAFLD and T2DM. This cross-sectional study involved 219 patients
      (77 NAFLD subjects; 33 males, 44 females; 142 T2DM subjects: 76 males, 66
      females) aged 40-79 years. Dietary intake was assessed using a validated self
      administered diet history questionnaire. Among the results, the most notable in
      NAFLD patients relative to T2DM patients were: 1) the low intake of vegetables
      that can reduce the overall energy density; 2) the high consumption of fruits and
      confectionery containing simple carbohydrates such as fructose; and 3) BMI may be
      higher. We demonstrated differences in dietary selection between the two groups.
      NAFLD patients were more likely to have dietary habits that promote fat
      accumulation in the body.

PMID- 27895390
TI  - Maslinic acid in olive fruit alleviates mild knee joint pain and improves quality
      of life by promoting weight loss in the elderly.
AB  - Consumption of olives (Olea europaea L.) is associated with a low incidence of
      inflammation-related diseases. Olive fruit is rich in bioactive pentacyclic
      triterpenoids, mainly maslinic acid. This study, a randomized, double-blind, and
      placebo-controlled trial, examined the effects of an orally administered maslinic
      acid supplement, olive fruit extract, on 20 middle-aged and elderly volunteers
      with mild knee joint pain. Each subject (58 +/- 7 years) received either olive
      fruit extract, containing 50 mg maslinic acid (n = 12), or placebo (n = 8) daily
      for 12 weeks and evaluated for pain and physical functions as primary outcome
      measures. Secondary outcome measures included body composition and inflammatory
      biomarkers in serum. Although both groups exhibited improved pain visual analogue
      scale score and quality of life after supplementation, symptoms were better in
      the maslinic acid group than in the placebo group. After 12 weeks, maslinic acid
      group exhibited significant decrease in body weight and body mass index
      suggesting that maslinic acid affected the weight of volunteers with mild knee
      joint pain. Therefore, olive products containing maslinic acid may be useful as a
      new preventive and therapeutic food ingredient for arthritic diseases. Since this
      clinical study is a preliminary study, it was not registered in a publicly
      accessible database.

PMID- 27895391
TI  - Characteristics of gastric cancer detected within 1 year after successful
      eradication of Helicobacter pylori.
AB  - Gastric cancers are sometimes diagnosed in patients who have successfully
      undergone Helicobacter pylori (H. pylori) eradication. We analyzed the
      clinicopathological features of gastric cancers detected after eradication to
      clarify their characteristics. We reviewed 31 patients with 34 cases of gastric
      cancer detected after successful H. pylori eradication. Clinicopathological
      characteristics analyzed included interval since eradication, interval since last
      endoscopy, tumor size, and depth of invasion. Patients were classified into two
      groups: early detection (<1 year since eradication) and delayed detection (>=1
      year since eradication). The interval since last endoscopy was significantly
      shorter in the early detection group than in the delayed detection group.
      However, gastric cancers were significantly larger and more invasive in the early
      detection group than in the delayed detection group. In conclusion, diligent
      endoscopy is necessary during the first year after successful H. pylori
      eradication. (The University Hospital Medical Information Network clinical trial
      registration number is UMIN000018541.).

PMID- 27895392
TI  - Determination of the adequate dosage of rebamipide, a gastric mucoprotective
      drug, to prevent low-dose aspirin-induced gastrointestinal mucosal injury.
AB  - Small intestinal mucosal injury caused by low-dose aspirin is a common cause of
      obscure gastrointestinal bleeding. We aimed to investigate the protective effects
      and optimal dose of rebamipide for low-dose aspirin-induced gastrointestinal
      mucosal injury. In this prospective randomized trial, 45 healthy volunteers (aged
      20-65 years) were included and divided into three groups. The groups received
      enteric-coated aspirin 100 mg (low-dose aspirin) plus omeprazole 10 mg (Group A:
      proton pump inhibitor group), low-dose aspirin plus rebamipide 300 mg (Group B:
      standard-dose group), or low-dose aspirin plus rebamipide 900 mg (Group C: high
      dose group). Esophagogastroduodenoscopy and video capsule endoscopy were
      performed, and the fecal occult blood reaction and fecal calprotectin levels were
      measured before and two weeks after drug administration. Although the fecal
      calprotectin levels increased significantly in Group A, they did not increase in
      Groups B and C. The esophagogastroduodenoscopic and video capsule endoscopic
      findings and the fecal occult blood test findings did not differ significantly
      among the three groups. In conclusion, standard-dose rebamipide is sufficient for
      preventing mucosal injury of the small intestine induced by low-dose aspirin,
      indicating that high-dose rebamipide is not necessary.

PMID- 27895393
TI  - Emerging role of obeticholic acid in the management of nonalcoholic fatty liver
      disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease
      and its prevalence is increasing driven by the pandemic of obesity and type 2
      diabetes mellitus. NAFLD can progress to cirrhosis and is associated with
      increased risk for cardiovascular disease and hepatocellular cancer. Diet and
      exercise are limited by suboptimal long-term adherence in patients with NAFLD. On
      the other hand, current pharmacological treatment of NAFLD has limited efficacy
      and unfavorable safety profile. In this context, obeticholic acid (OCA), a
      selective agonist of the farnesoid X receptors, might represent a useful option
      in these patients. Preclinical studies suggest that OCA improves hepatic
      steatosis, inflammation and fibrosis. A proof-of-concept study and the
      randomized, placebo-controlled Farnesoid X Receptor Ligand Obeticholic Acid in
      non-alcoholic steatohepatitis Treatment (FLINT) trial also showed improvements in
      liver histology in patients with NAFLD who received OCA. Weight loss and
      reduction in blood pressure were also observed. However, the effects of OCA on
      insulin resistance are conflicting and the lipid profile is adversely affected by
      this agent. In addition, pruritus is frequently observed during treatment with
      OCA and might lead to treatment discontinuation. However, given the limitations
      of existing treatments for NAFLD, OCA might represent a useful therapeutic option
      in selected patients with NAFLD.

PMID- 27895394
TI  - Concise review: Interferon-free treatment of hepatitis C virus-associated
      cirrhosis and liver graft infection.
AB  - Chronic hepatitis C is a major reason for development of cirrhosis and
      hepatocellular carcinoma and a leading cause for liver transplantation. The
      development of direct-acting antiviral agents lead to (pegylated) interferon-alfa
      free antiviral therapy regimens with a remarkable increase in sustained virologic
      response (SVR) rates and opened therapeutic options for patients with advanced
      cirrhosis and liver graft recipients. This concise review gives an overview about
      most current prospective trials and cohort analyses for treatment of patients
      with liver cirrhosis and liver graft recipients. In patients with compensated
      cirrhosis Child-Pugh-Turcotte (CTP) class A, all approved agents are safe and SVR
      rates do not significantly differ from patients without cirrhosis in general. In
      patients with decompensated cirrhosis CTP class B or C, daclastasvir, ledipasvir,
      velpatasvir, and sofosbuvir are approved, and SVR rates higher than 90% can be
      achieved. Especially for patients with a model of end stage liver disease score
      higher than 15 and therefore eligible for liver transplantation, data is scarce.
      Reported SVR rates in patients with cirrhosis CTP class C are lower compared to
      patients with a less severe liver disease. In liver transplant recipients with a
      maximum of CTP class A, SVR rates are comparable to patients without LT. Patients
      with decompensated graft cirrhosis should be treated on an individual basis.

PMID- 27895397
TI  - Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic
      steatohepatitis.
AB  - The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the
      metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from
      benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained
      inflammation in the liver is critical in this process. Hepatic macrophages,
      including liver resident macropaghes (Kupffer cells), monocytes infiltrating the
      injured liver, as well as specific lymphocytes subsets play a pivotal role in the
      initiation and perpetuation of the inflammatory response, with a major
      deleterious impact on the progression of fatty liver to fibrosis. During the last
      years, Th17 cells have been involved in the development of inflammation not only
      in liver but also in other organs, such as adipose tissue or lung.
      Differentiation of a naive T cell into a Th17 cell leads to pro-inflammatory
      cytokine and chemokine production with subsequent myeloid cell recruitment to the
      inflamed tissue. Th17 response can be mitigated by T regulatory cells that
      secrete anti-inflammatory cytokines. Both T cell subsets need TGF-beta for their
      differentiation and a characteristic plasticity in their phenotype may render
      them new therapeutic targets. In this review, we discuss the role of the Th17
      pathway in NAFLD progression to NASH and to liver fibrosis analyzing different
      animal models of liver injury and human studies.

PMID- 27895395
TI  - Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in
      gastroenterology.
AB  - The past decade has witnessed an outstanding scientific production focused
      towards the possible clinical applications of mesenchymal stromal cells (MSCs) in
      autoimmune and chronic inflammatory diseases. This raised the need of novel
      standards to adequately address quality, efficacy and safety issues of this
      advanced therapy. The development of a streamlined regulation is currently
      hampered by the complexity of analyzing dynamic biological entities rather than
      chemicals. Although numerous pieces of evidence show efficacy in reducing
      intestinal inflammation, some inconsistencies between the mechanisms of action of
      rodent vs human MSCs suggest caution before assigning translational value to
      preclinical studies. Preliminary evidence from clinical trials showed efficacy of
      MSCs in the treatment of fistulizing Crohn's disease (CD), and preparations of
      heterologous MSCs for CD treatment are currently tested in ongoing clinical
      trials. However, safety issues, especially in long-term treatment, still require
      solid clinical data. In this regard, standardized guidelines for appropriate
      dosing and methods of infusion could enhance the likelihood to predict more
      accurately the number of responders and the duration of remission periods. In
      addition, elucidating MSC mechanisms of action could lead to novel and more
      reliable formulations such as those derived from the MSCs themselves (e.g.,
      supernatants).

PMID- 27895398
TI  - Dysregulation of innate immunity in ulcerative colitis patients who fail anti
      tumor necrosis factor therapy.
AB  - AIM: To study the innate immune function in ulcerative colitis (UC) patients who
      fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of
      anti-TNF therapy, inflammation and medications on innate immune function were
      assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine
      expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti
      TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR
      stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n =
      12) and compared to healthy controls (n = 12). Erythrocyte sedimentation rate
      (ESR) and C-reactive protein (CRP) levels were measured in blood to assess
      disease severity/activity and inflammation. Pro-inflammatory (TNF, IL-1beta, IL
      6), immuno-regulatory (IL-10), Th1 (IL-12, IFNgamma) and Th2 (IL-9, IL-13, IL
      17A) cytokine expression was measured with enzyme-linked immunosorbent assay
      while TLR cellular composition and intracellular signalling was assessed with
      FACS. RESULTS: Prior to anti-TNF therapy, responders and non-responders had
      similar level of disease severity and activity. PBMC's ability to respond to TLR
      stimulation was not affected by TNF therapy, patient's severity of the disease
      and inflammation or their medication use. At baseline, non-responders had
      elevated innate but not adaptive immune responses compared to responders (P <
      0.05). Following TLR stimulation, non-responders had consistently reduced innate
      cytokine responses to all TLRs compared to healthy controls (P < 0.01) and
      diminished TNF (P < 0.001) and IL-1beta (P < 0.01) production compared to
      responders. This innate immune dysfunction was associated with reduced number of
      circulating plasmacytoid dendritic cells (pDCs) (P < 0.01) but increased number
      of CD4+ regulatory T cells (Tregs) (P = 0.03) as well as intracellular
      accumulation of IRAK4 in non-responders following TLR-2, -4 and -7 activation (P
      < 0.001). CONCLUSION: Reduced innate immunity in non-responders may explain
      reduced efficacy to anti-TNF therapy. These serological markers may prove useful
      in predicting the outcome of costly anti-TNF therapy.

PMID- 27895399
TI  - Altered pattern of tumor necrosis factor-alpha production in peripheral blood
      monocytes from Crohn's disease.
AB  - AIM: To evaluate the inflammatory state in Crohn's disease (CD) patients and
      correlate it with genetic background and microbial spreading. METHODS: By means
      of flow cytometry, production of tumor necrosis factor-alpha (TNF-alpha) was
      measured in peripheral blood monocytes from patients suffering from CD,
      ulcerative colitis (UC) and in healthy subjects after stimulation of the NOD2 and
      TLR pathways. CD patients were genotyped for the three most common NOD2 variants
      (R702W, G908R and L1007Pfs*2) and basal production of TNF-alpha was correlated to
      NOD2 genotype. Also, production of TNF-alpha was correlated to plasmatic levels
      of LPS Binding Protein (LBP), soluble (s) CD14 and to the activity state of the
      disease. RESULTS: The patients with CD were characterized by a significantly
      higher monocyte basal expression of TNF-alpha compared with healthy subjects and
      UC patients, and after stimulation with Pam3CSK4 (ligand of TLR2/1) and MDP-L18
      (ligand of NOD2) this difference was maintained, while other microbial stimuli
      (LPS, ligand of TLR4 and PolyI:C, ligand of TLR3) induced massive activation in
      CD monocytes as well as in UC and in healthy control cells. There was no
      significant difference in the production of TNF-alpha between patients who
      carried CD-associated heterozygous or homozygous variants in NOD2 and patients
      with wild type NOD2 genotype. Although serum LBP levels have been shown to
      correlate positively with the state of activity of the disease, TNF-alpha
      production did not show a clear correlation with either LBP or sCD14 levels in
      plasma. Moreover, no clear correlation was seen between TNF-alpha production and
      activity indices in either CD or UC. CONCLUSION: Peripheral monocytes from CD
      express higher basal and stimulated TNF-alpha than controls, regardless of NOD2
      genotype and without a clear correlation with disease activity.

PMID- 27895400
TI  - Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine,
      aggravated by L-NAME.
AB  - AIM: To cure typically life-threatening esophagogastric anastomosis in rats,
      lacking anastomosis healing and sphincter function rescue, in particular.
      METHODS: Because we assume esophagogastric fistulas represent a particular NO
      system disability, we attempt to identify the benefits of anti-ulcer stable
      gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and
      currently for multiple sclerosis, in rats with esophagocutaneous fistulas.
      Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis
      and fistulas, and esophagitis and gastric lesions, along with rescued sphincter
      function. Additionally, BPC 157 particularly interacts with the NO-system. In the
      4 d after esophagogastric anastomosis creation, rats received medication (/kg
      intraperitoneally once daily: BPC 157 (10 MUg, 10 ng), L-NAME (5 mg), or L
      arginine (100 mg) alone and/or combined or BPC 157 (10 MUg, 10 ng) in drinking
      water). For rats underwent esophagogastric anastomosis, daily assessment included
      progressive stomach damage (sum of the longest diameters, mm), esophagitis
      (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at
      anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g)
      and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5)
      at the stomach surface immediately after anastomosis creation. RESULTS: BPC 157
      (all regimens) fully counteracted the perilous disease course from the very
      beginning (i.e., with the BPC 157 bath, blood vessels remained present at the
      gastric surface after anastomosis creation) and eliminated mortality.
      Additionally, BPC 157 treatment in combination with L-NAME nullified any effect
      of L-NAME that otherwise intensified the regular course. Consistently, with
      worsening (with L-NAME administration) and amelioration (with L-arginine), either
      L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or
      they counteract each other (L-NAME + L-arginine); with the addition of BPC 157 (L
      NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157
      treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or
      NOS substrate L-arginine, demonstrated an innate NO-system disability (as
      observed with L-arginine effectiveness). BPC 157 distinctively affected
      corresponding events: worsening (obtained with L-NAME administration that was
      counteracted); or amelioration (L-arginine + BPC 157-rats correspond to BPC 157
      rats). CONCLUSION: Innate NO-system disability for esophagogastric anastomoses,
      including L-NAME-worsening, suggests that these effects could be corrected by L
      arginine and almost completely eliminated by BPC 157 therapy.

PMID- 27895402
TI  - Effect of airplane transport of donor livers on post-liver transplantation
      survival.
AB  - AIM: To evaluate the effect of long haul airplane transport of donor livers on
      post-transplant outcomes. METHODS: A retrospective cohort study of patients who
      received a liver transplantation was performed in Perth, Australia from 1992 to
      2012. Donor and recipient characteristics information were extracted from Western
      Australian liver transplantation service database. Patients were followed up for
      a mean of six years. Patient and graft survival were evaluated and compared
      between patients who received a local donor liver and those who received an
      airplane transported donor liver. Predictors of survival were determined by
      univariate and multivariate analysis using cox regression. RESULTS: One hundred
      and ninety-three patients received a local donor liver and 93 patients received
      an airplane transported donor liver. Airplane transported livers had a
      significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035),
      higher donor risk index (mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic
      time (CIT) (mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation
      between CIT and transport distance (r2 = 0.29, P < 0.001). Mean follow up was six
      years and 93 patients had graft failure. Multivariate analysis found only
      airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16
      3.17). One year graft survival was 0.88 for those with a local liver and was 0.71
      for those with an airplane transported liver. One year graft loss was due to
      primary graft non-function or associated with preservation injury in 20.8% of
      recipients of an airplane transported liver compared with 4.6% in those with a
      local liver (P = 0.027). CONCLUSION: Airplane transport of donor livers was
      independently associated with reduced graft survival following liver
      transplantation.

PMID- 27895401
TI  - HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric
      cancer.
AB  - AIM: To investigated the relationships between HER2, c-Jun N-terminal kinase
      (JNK) and protein kinase B (AKT) with respect to metastatic potential of HER2
      positive gastric cancer (GC) cells. METHODS: Immunohistochemistry was performed
      on tissue array slides containing 423 human GC specimens. Using HER2-positve GC
      cell lines SNU-216 and NCI-N87, HER2 expression was silenced by RNA interference,
      and the activations of JNK and AKT were suppressed by SP600125 and LY294002,
      respectively. Transwell assay, Western blot, semi-quantitative reverse
      transcription-polymerase chain reaction and immunofluorescence staining were used
      in cell culture experiments. RESULTS: In GC specimens, HER2, JNK, and AKT
      activations were positively correlated with each other. In vitro analysis
      revealed a positive regulatory feedback loop between HER2 and JNK in GC cell
      lines and the role of JNK as a downstream effector of AKT in the HER2/AKT
      signaling pathway. JNK inhibition suppressed migratory capacity through reversing
      EMT and dual inhibition of JNK and AKT induced a more profound effect on cancer
      cell motility. CONCLUSION: HER2, JNK and AKT in human GC specimens are positively
      associated with each other. JNK and AKT, downstream effectors of HER2, co
      operatively contribute to the metastatic potential of HER2-positive GC cells.
      Thus, targeting of these two molecules in combination with HER2 downregulation
      may be a good approach to combat HER2-positive GC.

PMID- 27895403
TI  - First-line endoscopic treatment with over-the-scope clips significantly improves
      the primary failure and rebleeding rates in high-risk gastrointestinal bleeding:
      A single-center experience with 100 cases.
AB  - AIM: To evaluate rebleeding, primary failure (PF) and mortality of patients in
      whom over-the-scope clips (OTSCs) were used as first-line and second-line
      endoscopic treatment (FLET, SLET) of upper and lower gastrointestinal bleeding
      (UGIB, LGIB). METHODS: A retrospective analysis of a prospectively collected
      database identified all patients with UGIB and LGIB in a tertiary endoscopic
      referral center of the University of Freiburg, Germany, from 04-2012 to 05-2016
      (n = 93) who underwent FLET and SLET with OTSCs. The complete Rockall risk scores
      were calculated from patients with UGIB. The scores were categorized as < or >= 7
      and were compared with the original Rockall data. Differences between FLET and
      SLET were calculated. Univariate and multivariate analysis were performed to
      evaluate the factors that influenced rebleeding after OTSC placement. RESULTS:
      Primary hemostasis and clinical success of bleeding lesions (without rebleeding)
      was achieved in 88/100 (88%) and 78/100 (78%), respectively. PF was significantly
      lower when OTSCs were applied as FLET compared to SLET (4.9% vs 23%, P = 0.008).
      In multivariate analysis, patients who had OTSC placement as SLET had a
      significantly higher rebleeding risk compared to those who had FLET (OR 5.3; P =
      0.008). Patients with Rockall risk scores >= 7 had a significantly higher in
      hospital mortality compared to those with scores < 7 (35% vs 10%, P = 0.034). No
      significant differences were observed in patients with scores < or >= 7 in
      rebleeding and rebleeding-associated mortality. CONCLUSION: Our data show for the
      first time that FLET with OTSC might be the best predictor to successfully
      prevent rebleeding of gastrointestinal bleeding compared to SLET. The type of
      treatment determines the success of primary hemostasis or primary failure.

PMID- 27895396
TI  - Genetic alterations in hepatocellular carcinoma: An update.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related
      deaths worldwide. Although recent advances in therapeutic approaches for treating
      HCC have improved the prognoses of patients with HCC, this cancer is still
      associated with a poor survival rate mainly due to late diagnosis. Therefore, a
      diagnosis must be made sufficiently early to perform curative and effective
      treatments. There is a need for a deeper understanding of the molecular
      mechanisms underlying the initiation and progression of HCC because these
      mechanisms are critical for making early diagnoses and developing novel
      therapeutic strategies. Over the past decade, much progress has been made in
      elucidating the molecular mechanisms underlying hepatocarcinogenesis. In
      particular, recent advances in next-generation sequencing technologies have
      revealed numerous genetic alterations, including recurrently mutated genes and
      dysregulated signaling pathways in HCC. A better understanding of the genetic
      alterations in HCC could contribute to identifying potential driver mutations and
      discovering novel therapeutic targets in the future. In this article, we
      summarize the current advances in research on the genetic alterations, including
      genomic instability, single-nucleotide polymorphisms, somatic mutations and
      deregulated signaling pathways, implicated in the initiation and progression of
      HCC. We also attempt to elucidate some of the genetic mechanisms that contribute
      to making early diagnoses of and developing molecularly targeted therapies for
      HCC.

PMID- 27895405
TI  - Impact of IL28B and OAS gene family polymorphisms on interferon treatment
      response in Caucasian children chronically infected with hepatitis B virus.
AB  - AIM: To investigate the impact of IL28B and OAS gene polymorphisms on interferon
      treatment responses in children with chronic hepatitis B. METHODS: We enrolled 52
      children (between the ages of 4 and 18) with hepatitis B e antigen-negative
      chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48
      wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747),
      OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and
      rs8099917) genes were studied to examine their associations with responses to IFN
      treatment in paediatric patients. We adopted two criteria for the therapeutic
      response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and
      normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared
      the patients in terms of achieving a partial response (PR) and a complete
      response (CR) upon measurement at the 24-wk post-treatment follow-up. RESULTS:
      The PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age,
      gender and liver histology had no impact on the type of response (partial or
      complete). A statistically significant relationship between higher baseline HBV
      DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05).
      The allele association analysis revealed that only the IL-28B rs12979860 (C vs T)
      and IL28B rs12980275 (A vs G) markers significantly affected the achievement of
      PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1,
      respectively). However, in the genotype analysis, only IL-28B rs12980275 was
      significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3
      93.9). The association analysis for CR showed that the TT genotype of IL28B
      rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of
      OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR
      = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant
      associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001,
      respectively), but no association with IL28B haplotype was observed. CONCLUSION:
      IL28B and OAS polymorphisms are associated with different clinical outcomes in
      CHB children treated with interferon.

PMID- 27895406
TI  - Simplified criteria for diagnosing superficial esophageal squamous neoplasms
      using Narrow Band Imaging magnifying endoscopy.
AB  - AIM: To simplify the diagnostic criteria for superficial esophageal squamous cell
      carcinoma (SESCC) on Narrow Band Imaging combined with magnifying endoscopy (NBI
      ME). METHODS: This study was based on the post-hoc analysis of a randomized
      controlled trial. We performed NBI-ME for 147 patients with present or a history
      of squamous cell carcinoma in the head and neck, or esophagus between January
      2009 and June 2011. Two expert endoscopists detected 89 lesions that were
      suspicious for SESCC lesions, which had been prospectively evaluated for the
      following 6 NBI-ME findings in real time: "intervascular background coloration";
      "proliferation of intrapapillary capillary loops (IPCL)"; and "dilation",
      "tortuosity", "change in caliber", and "various shapes (VS)" of IPCLs (i.e.,
      Inoue's tetrad criteria). The histologic examination of specimens was defined as
      the gold standard for diagnosis. A stepwise logistic regression analysis was used
      to identify candidates for the simplified criteria from among the 6 NBI-ME
      findings for diagnosing SESCCs. We evaluated diagnostic performance of the
      simplified criteria compared with that of Inoue's criteria. RESULTS: Fifty-four
      lesions (65%) were histologically diagnosed as SESCCs and the others as low-grade
      intraepithelial neoplasia or inflammation. In the univariate analysis,
      proliferation, tortuosity, change in caliber, and VS were significantly
      associated with SESCC (P < 0.01). The combination of VS and proliferation was
      statistically extracted from the 6 NBI-ME findings by using the stepwise logistic
      regression model. We defined the combination of VS and proliferation as
      simplified dyad criteria for SESCC. The areas under the curve of the simplified
      dyad criteria and Inoue's tetrad criteria were 0.70 and 0.73, respectively. No
      significant difference was shown between them. The sensitivity, specificity, and
      accuracy of diagnosis for SESCC were 77.8%, 57.1%, 69.7% and 51.9%, 80.0%, 62.9%
      for the simplified dyad criteria and Inoue's tetrad criteria, respectively.
      CONCLUSION: The combination of proliferation and VS may serve as simplified
      criteria for the diagnosis of SESCC using NBI-ME.

PMID- 27895407
TI  - Assessment of scoring systems for acute-on-chronic liver failure at predicting
      short-term mortality in patients with alcoholic hepatitis.
AB  - AIM: To assess the performance of proposed scores specific for acute-on-chronic
      liver failure in predicting short-term mortality among patients with alcoholic
      hepatitis. METHODS: We retrospectively collected data from 264 patients with
      clinically diagnosed alcoholic hepatitis from January to December 2013 at 21
      academic hospitals in Korea. The performance for predicting short-term mortality
      was calculated for Chronic Liver Failure-Sequential Organ Failure Assessment
      (CLIF-SOFA), CLIF Consortium Organ Failure score (CLIF-C OFs), Maddrey's
      discriminant function (DF), age, bilirubin, international normalized ratio and
      creatinine score (ABIC), Glasgow Alcoholic Hepatitis Score (GAHS), model for end
      stage liver disease (MELD), and MELD-Na. RESULTS: Of 264 patients, 32 (12%)
      patients died within 28 d. The area under receiver operating characteristic curve
      of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86 (0.81-0.90),
      0.89 (0.84-0.92), 0.79 (0.74-0.84), 0.78 (0.72-0.83), 0.81 (0.76-0.86), 0.83
      (0.78-0.88), and 0.83 (0.78-0.88), respectively, for 28-d mortality. The
      performance of CLIF-SOFA had no statistically significant differences for 28-d
      mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and
      GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality.
      A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C
      OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d
      mortality. CONCLUSION: CLIF-SOFA and CLIF-C OF scores performed well, with
      comparable predictive ability for short-term mortality compared to the commonly
      used scoring systems in patients with alcoholic hepatitis.

PMID- 27895404
TI  - Presepsin teardown - pitfalls of biomarkers in the diagnosis and prognosis of
      bacterial infection in cirrhosis.
AB  - AIM: To evaluate the diagnostic and prognostic value of presepsin in cirrhosis
      associated bacterial infections. METHODS: Two hundred and sixteen patients with
      cirrhosis were enrolled. At admission, the presence of bacterial infections and
      level of plasma presepsin, serum C-reactive protein (CRP) and procalcitonin (PCT)
      were evaluated. Patients were followed for three months to assess the possible
      association between presepsin level and short-term mortality. RESULTS: Present
      34.7 of patients had bacterial infection. Presepsin levels were significantly
      higher in patients with infection than without (median, 1002 pg/mL vs 477 pg/mL,
      P < 0.001), increasing with the severity of infection [organ failure (OF): Yes vs
      No, 2358 pg/mL vs 710 pg/mL, P < 0.001]. Diagnostic accuracy of presepsin for
      severe infections was similar to PCT and superior to CRP (AUC-ROC: 0.85, 0.85 and
      0.66, respectively, P = NS for presepsin vs PCT and P < 0.01 for presepsin vs
      CRP). At the optimal cut-off value of presepsin > 1206 pg/mL sensitivity,
      specificity, positive predictive values and negative predictive values were as
      follows: 87.5%, 74.5%, 61.8% and 92.7%. The accuracy of presepsin, however,
      decreased in advanced stage of the disease or in the presence of renal failure,
      most probably because of the significantly elevated presepsin levels in non
      infected patients. 28-d mortality rate was higher among patients with > 1277
      pg/mL compared to those with <= 1277 pg/mL (46.9% vs 11.6%, P < 0.001). In a
      binary logistic regression analysis, however, only PCT (OR = 1.81, 95%CI: 1.09
      3.01, P = 0.022) but neither presepsin nor CRP were independent risk factor for
      28-d mortality after adjusting with MELD score and leukocyte count. CONCLUSION:
      Presepsin is a valuable new biomarker for defining severe infections in
      cirrhosis, proving same efficacy as PCT. However, it is not a useful marker of
      short-term mortality.

PMID- 27895409
TI  - Two cases of pancreatic ductal adenocarcinoma with intrapancreatic metastasis.
AB  - There are no standardized diagnostic criteria for intrapancreatic metastasis of
      pancreatic ductal adenocarcinoma (PDAC). Here, we report two cases of patients
      with PDAC who were pathologically diagnosed as harboring intrapancreatic
      metastasis. In both cases, the main lesions were located in the pancreatic body,
      and no other lesion was detected preoperatively. The patients were diagnosed with
      pancreatic body cancers and distal pancreatectomy was performed. Pathological
      findings revealed microscopic cancer nests, which had connections to neither the
      main lesion nor the premalignant lesion in the pancreatic tail parenchyma. In
      both cases, the histological type of the daughter lesion was quite similar to
      that of the main lesion. Hence, we diagnosed the daughter lesions as metastatic
      foci in the pancreas. Although intrapancreatic metastasis of PDAC has been
      regarded as a poor prognostic factor, few reports of intrapancreatic metastasis
      are available. This article reports two such cases and provides a review of the
      literature.

PMID- 27895408
TI  - Molecular detection of Helicobacter pylori antibiotic resistance in stool vs
      biopsy samples.
AB  - AIM: To compare (1) demographics in urea breath test (UBT) vs endoscopy patients;
      and (2) the molecular detection of antibiotic resistance in stool vs biopsy
      samples. METHODS: Six hundred and sixteen adult patients undergoing endoscopy or
      a UBT were prospectively recruited to the study. The GenoType HelicoDR assay was
      used to detect Helicobacter pylori (H. pylori) and antibiotic resistance using
      biopsy and/or stool samples from CLO-positive endoscopy patients and stool
      samples from UBT-positive patients. RESULTS: Infection rates were significantly
      higher in patients referred for a UBT than endoscopy (overall rates: 33% vs 19%;
      treatment-naive patients: 33% vs 14.7%, respectively). H. pylori-infected UBT
      patients were younger than H. pylori-infected endoscopy patients (41.4 vs 48.4
      years, respectively, P < 0.005), with a higher percentage of H. pylori-infected
      males in the endoscopy-compared to the UBT-cohort (52.6% vs 33.3%, P = 0.03). The
      GenoType HelicoDR assay was more accurate at detecting H. pylori infection using
      biopsy samples than stool samples [98.2% (n = 54/55) vs 80.3% (n =53/66), P <
      0.005]. Subset analysis using stool and biopsy samples from CLO-positive
      endoscopy patients revealed a higher detection rate of resistance-associated
      mutations using stool samples compared to biopsies. The concordance rates between
      stool and biopsy samples for the detection of H. pylori DNA, clarithromycin and
      fluoroquinolone resistance were just 85%, 53% and 35%, respectively. CONCLUSION:
      Differences between endoscopy and UBT patients provide a rationale for non
      invasive detection of H. pylori antibiotic resistance. However, the GenoType
      HelicoDR assay is an unsuitable approach.

PMID- 27895410
TI  - Collision tumor of hepatocellular carcinoma and neuroendocrine carcinoma
      involving the liver: Case report and review of the literature.
AB  - Primary hepatic neuroendocrine carcinoma (NEC) with concurrent occurrence of
      hepatocellular carcinoma (HCC) of the liver is very rare. Only 8 cases have been
      reported in the literature. Concurrent occurrence of HCC and NEC in the liver is
      classified as combined type or collision type by histological distributional
      patterns; only 2 cases have been reported. Herein, we report a case of collision
      type concurrent occurrence of HCC and NEC, in which primary hepatic NEC was in
      only a small portion of the nodule, which is different from the 2 previously
      reported cases. A 72-year-old male with chronic hepatitis C was admitted to our
      hospital for a hepatic mass detected by liver computed tomography (CT) at another
      clinic. Because the nodule was in hepatic segment 3 and had proper radiologic
      findings for diagnosis of HCC, including enhancement in the arterial phase and
      wash-out in the portal and delay phases, the patient was treated with
      laparoscopic left lateral sectionectomy. The pathology demonstrated that the
      nodule was 2.5 cm and was moderately differentiated HCC. However, a 3 mm-sized
      focal neuroendocrine carcinoma was also detected on the capsule of the nodule.
      The tumor was concluded to be a collision type with HCC and primary hepatic NEC.
      After the surgery, for follow-up, the patient underwent a liver CT every 3 mo.
      Five multiple nodules were found in the right hepatic lobe on the follow-up liver
      CT 6 mo post-operatively. As the features of the nodules in the liver CT and MRI
      were different from that of HCC, a liver biopsy was performed. Intrahepatic
      recurrent NEC was proven after the liver biopsy, which showed the same pathologic
      features with the specimen obtained 6 mo ago. Palliative chemotherapy with a
      combination of etoposide and cisplatin has been administered for 4 months,
      showing partial response.

PMID- 27895411
TI  - Reoperation in an adult female with "right-sided" Hirschsprung's disease
      complicated by refractory hypertension and cough.
AB  - Hirschsprung's disease (HD) is an intestinal malformation caused by the innate
      absence of ganglion cells in the neural plexus of the colorectal wall, and is
      most common in male infants. It is rare in adult, and is usually left-sided.
      Herein we reported based on the CARE guidelines a case of a 47-year-old adult
      female suffering from "right-sided" HD complicated by refractory hypertension and
      cough. The patient with a history of cesarean section and with digestive
      unfitness (abdominal pain, distention, and constipation) only since 20 years old
      had recurrence of HD after initial surgery due to the incomplete removal of the
      HD-affected bowel based on a diagnosis of "chronic ileus", leading to the relapse
      of the digestive symptoms and the emergence of some intractable circulatory and
      respiratory complications which could be hardly controlled by conservative
      treatment. During the long interval before coming to our department for help, she
      had been re-hospitalized for several times with various misdiagnoses and supplied
      merely with symptomatic treatment which could only achieve temporary symptomatic
      relief. At her admission to our department, the imaging examinations strongly
      indicated recurrent HD which was further supported by pathological examinations,
      and right hemi-colectomy was performed to remove the remnant aganglionic
      intestinal segment. Intraoperative and postoperative pathology supported the
      completeness of the definitive resection. Post-operation, the patient's bowel
      motility significantly improved, and interestingly, the complications
      disappeared. For adult patients with long-term constipation combined with cough
      and hypertension, rare diseases like HD which requires definite surgery and which
      could be "right-sided" should not be overlooked. It is vital to diagnose and cure
      HD patients in childhood. Through the comparison of the two surgeries, it is
      noteworthy that for diagnosed HD, sufficient removal of the non-functional
      intestine confirmed by intraoperative pathology is essential.

PMID- 27895412
TI  - Metabolic imaging for guidance of curative treatment of isolated pelvic
      implantation metastasis after resection of spontaneously ruptured hepatocellular
      carcinoma: A case report.
AB  - Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening
      complication and its prognosis is significantly poor because of the high
      recurrence rate after initial hepatectomy. Resection of isolated extrahepatic
      metastasis of HCC has been advocated to obtain a possibility of long-term
      survival. However, it is a challenge for clinicians to detect implantation
      metastasis of spontaneously ruptured HCC. Accurate re-staging plays the most
      important role in making a decision on isolated metastasis resection. 18F
      fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography
      (PET/CT) is useful in detecting intra-abdominal implantation metastasis from a
      variety of malignancies and shows superior accuracy to conventional imaging
      modalities in determining the location of metastasis. We present one patient with
      a new isolated pelvic implantation metastasis detected by 18F-FDG PET/CT and
      pathologically confirmed by PET/CT-guided percutaneous biopsy, who had a history
      of resection of spontaneously ruptured HCC two years ago. The patient's condition
      was stable at the 6-mo follow-up after resection of the isolated pelvic
      metastasis.

PMID- 27895413
TI  - Hepatic epithelioid hemangioendothelioma: Dilemma and challenges in the
      preoperative diagnosis.
AB  - Hepatic epithelioid hemangioendothelioma (HEHE) is a rare category of vascular
      tumor with uncertain malignant potential. It commonly presents nonspecific and
      variable clinical manifestations, ranging from asymptomatic to hepatic failure.
      In addition, laboratory measurements and imaging features also lack specificity
      in the diagnosis of HEHE. The aim of the present study is to highlight the
      dilemma and challenges in the preoperative diagnosis of HEHE, and to enhance
      awareness of the range of hepatobiliary surgery available in patients with
      multiple hepatic nodular lesions on imaging. In these patients, HEHE should at
      least be considered in the differential diagnosis.

PMID- 27895414
TI  - Hepatic encephalopathy: Ever closer to its big bang.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric disorder that commonly
      complicates the course of patients with liver disease. Despite the fact that the
      syndrome was probably first recognized hundreds of years ago, the exact
      pathogenesis still remains unclear. Minimal hepatic encephalopathy (MHE) is the
      earliest form of HE and is estimated to affect more that 75% of patients with
      liver cirrhosis. It is characterized by cognitive impairment predominantly
      attention, reactiveness and integrative function with very subtle clinical
      manifestations. The development of MHE is associated with worsen in driving
      skills, daily activities and the increase of overall mortality. Skeletal muscle
      has the ability to shift from ammonia producer to ammonia detoxifying organ. Due
      to its large size, becomes the main ammonia detoxifying organ in case of chronic
      liver failure and muscular glutamine-synthase becomes important due to the
      failing liver and brain metabolic activity. Gut is the major glutamine consumer
      and ammonia producer organ in the body. Hepatocellular dysfunction due to liver
      disease, results in an impaired clearance of ammonium and in its inter-organ
      trafficking. Intestinal bacteria, can also represent an extra source of ammonia
      production and in cirrhosis, small intestinal bacterial overgrowth and symbiosis
      can be observed. In the study of HE, to get close to MHE is to get closer to its
      big bang; and from here, to travel less transited roads such as skeletal muscle
      and intestine, is to go even closer. The aim of this editorial is to expose this
      road for further and deeper work.

PMID- 27895416
TI  - Practice guidelines for the pathological diagnosis of primary liver cancer: 2015
      update.
AB  - In 2010, a panel of Chinese pathologists reported the first expert consensus for
      the pathological diagnosis of primary liver cancers to address the many
      contradictions and inconsistencies in the pathological characteristics and
      diagnostic criteria for PLC. Since then considerable clinicopathological studies
      have been conducted globally, prompting us to update the practice guidelines for
      the pathological diagnosis of PLC. In April 18, 2014, a Guideline Committee
      consisting of 40 specialists from seven Chinese Societies (including Chinese
      Society of Liver Cancer, Chinese Anti-Cancer Association; Liver Cancer Study
      Group, Chinese Society of Hepatology, Chinese Medical Association; Chinese
      Society of Pathology, Chinese Anti-Cancer Association; Digestive Disease Group,
      Chinese Society of Pathology, Chinese Medical Association; Chinese Society of
      Surgery, Chinese Medical Association; Chinese Society of Clinical Oncology,
      Chinese Anti-Cancer Association; Pathological Group of Hepatobiliary Tumor and
      Liver Transplantation, Chinese Society of Pathology, Chinese Medical Association)
      was created for the formulation of the first guidelines for the standardization
      of the pathological diagnosis of PLC, mainly focusing on the following topics:
      gross specimen sampling, concepts and diagnostic criteria of small hepatocellular
      carcinoma (SHCC), microvascular invasion (MVI), satellite nodules, and
      immunohistochemical and molecular diagnosis. The present updated guidelines are
      reflective of current clinicopathological studies, and include a novel 7-point
      baseline sampling protocol, which stipulate that at least four tissue specimens
      should be sampled at the junction of the tumor and adjacent liver tissues in a
      1:1 ratio at the 12, 3, 6 and 9 o'clock reference positions. For the purposes of
      molecular pathological examination, at least one specimen should be sampled at
      the intratumoral zone, but more specimens should be sampled for tumors harboring
      different textures or colors. Specimens should be sampled at both adjacent and
      distant peritumoral liver tissues or the tumor margin in order to observe MVI,
      satellite nodules and dysplastic foci/nodules distributed throughout the
      background liver tissues. Complete sampling of whole SHCC <= 3 cm should be
      performed to assess its biological behavior, and in clinical practice,
      therapeutic borders should be also preserved, even in SHCC. The diagnostic
      criteria of MVI and satellite nodules, immunohistochemical panels, as well as
      molecular diagnostic principles, such as clonal typing, for recurrent HCC and
      multinodule HCC were also proposed and recommended. The standardized process of
      pathological examination is aimed at ensuring the accuracy of pathological PLC
      diagnoses as well as providing a valuable frame of reference for the clinical
      assessment of tumor invasive potential, the risk of postoperative recurrence,
      long-term survival, and the development of individualized treatment regimens. The
      updated guidelines could ensure the accuracy of pathological diagnoses of PLC,
      and provide a valuable frame of reference for its clinical assessment.

PMID- 27895418
TI  - Molecular mechanism of action of anti-tumor necrosis factor antibodies in
      inflammatory bowel diseases.
AB  - Anti-tumor necrosis factor (TNF) antibodies are successfully used in the therapy
      of inflammatory bowel diseases (IBD). However, the molecular mechanism of action
      of these agents is still a matter of debate. Apart from neutralization of TNF,
      influence on the intestinal barrier function, induction of apoptosis in mucosal
      immune cells, formation of regulatory macrophages as well as other immune
      modulating properties have been discussed as central features. Nevertheless,
      clinically effective anti-TNF antibodies were shown to differ in their mode-of
      action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is
      effective in the treatment of rheumatoid arthritis but failed to induce clinical
      response in Crohn's disease patients, suggesting different contributions of TNF
      in the pathogenesis of these inflammatory diseases. In the following, we will
      review different aspects regarding the mechanism of action of anti-TNF agents in
      general and analyze comparatively different effects of each anti-TNF agent such
      as TNF neutralization, modulation of the immune system, reverse signaling and
      induction of apoptosis. We discuss the relevance of the membrane-bound form of
      TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore,
      we review reports that could lead to personalized medicine approaches regarding
      treatment with anti-TNF antibodies in chronic intestinal inflammation, by
      predicting response to therapy.

PMID- 27895417
TI  - Glycoproteins and glycoproteomics in pancreatic cancer.
AB  - Aberrations in protein glycosylation and polysaccharides play a pivotal role in
      pancreatic tumorigenesis, influencing cancer progression, metastasis, immuno
      response and chemoresistance. Abnormal expression in sugar moieties can impact
      the function of various glycoproteins, including mucins, surface receptors,
      adhesive proteins, proteoglycans, as well as their effectors and binding ligands,
      resulting in an increase in pancreatic cancer invasiveness and a cancer-favored
      microenvironment. Recent advance in glycoproteomics, glycomics and other chemical
      biology techniques have been employed to better understand the complex mechanism
      of glycosylation events and how they orchestrate molecular activities in
      genomics, proteomics and metabolomics implicated in pancreatic adenocarcinoma. A
      variety of strategies have been demonstrated targeting protein glycosylation and
      polysaccharides for diagnostic and therapeutic development.

PMID- 27895420
TI  - Clinical relevance of endoscopic assessment of inflammation in ulcerative
      colitis: Can endoscopic evaluation predict outcomes?
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel condition characterised
      by a relapsing and remitting course. Symptom control has been the traditional
      mainstay of medical treatment. It is well known that histological inflammatory
      activity persists despite adequate symptom control and absence of endoscopic
      inflammation. Current evidence suggests that presence of histological
      inflammation poses a greater risk of disease relapse and subsequent colorectal
      cancer risk. New endoscopic technologies hold promise for developing endoscopic
      markers of mucosal inflammation. Achieving endoscopic and histological remission
      appears be the future aim of medical treatments for UC. This review article aims
      to evaluate the use of endoscopy as a tool in assessment of mucosal inflammation
      UC and its correlation with disease outcomes.

PMID- 27895415
TI  - Factoring the intestinal microbiome into the pathogenesis of autoimmune
      hepatitis.
AB  - The intestinal microbiome is a reservoir of microbial antigens and activated
      immune cells. The aims of this review were to describe the role of the intestinal
      microbiome in generating innate and adaptive immune responses, indicate how these
      responses contribute to the development of systemic immune-mediated diseases, and
      encourage investigations that improve the understanding and management of
      autoimmune hepatitis. Alterations in the composition of the intestinal microflora
      (dysbiosis) can disrupt intestinal and systemic immune tolerances for commensal
      bacteria. Toll-like receptors within the intestine can recognize microbe
      associated molecular patterns and shape subsets of T helper lymphocytes that may
      cross-react with host antigens (molecular mimicry). Activated gut-derived
      lymphocytes can migrate to lymph nodes, and gut-derived microbial antigens can
      translocate to extra-intestinal sites. Inflammasomes can form within hepatocytes
      and hepatic stellate cells, and they can drive the pro-inflammatory, immune
      mediated, and fibrotic responses. Diet, designer probiotics, vitamin supplements,
      re-colonization methods, antibiotics, drugs that decrease intestinal
      permeability, and molecular interventions that block signaling pathways may
      emerge as adjunctive regimens that complement conventional immunosuppressive
      management. In conclusion, investigations of the intestinal microbiome are
      warranted in autoimmune hepatitis and promise to clarify pathogenic mechanisms
      and suggest alternative management strategies.

PMID- 27895421
TI  - Carbon monoxide contributes to the constipating effects of granisetron in rat
      colon.
AB  - AIM: To investigate the mechanisms underlying the potential contribution of the
      heme oxygenase/carbon monoxide (HO/CO) pathway in the constipating effects of
      granisetron. METHODS: For in vivo studies, gastrointestinal motility was
      evaluated in male rats acutely treated with granisetron [25, 50, 75
      MUg/kg/subcutaneous (sc)], zinc protoporphyrin IX [ZnPPIX, 50
      MUg/kg/intraperitoneal (ip)] and hemin (50 MUmol/L/kg/ip), alone or in
      combination. For in vitro studies, the contractile neurogenic response to
      electrical field stimulation (EFS, 3, 5, 10 Hz, 14 V, 1 ms, pulse trains lasting
      10 s), as well as the contractile myogenic response to acetylcholine (ACh, 0.1
      100 MUmol/L) were evaluated on colon specimens incubated with granisetron (3
      MUmol/L, 15 min), ZnPPIX (10 MUmol/L, 60 min) or CO-releasing molecule-3 (CORM-3,
      100, 200, 400 MUmol/L) alone or in combination. These experiments were performed
      under co-treatment with or without atropine (3 MUmol/L, a muscarinic receptor
      antagonist) or NG-nitro-L-Arginine (L-NNA, 100 MUmol/L, a nitric oxide synthase
      inhibitor). RESULTS: Administration of granisetron (50, 75 MUg/kg) in vivo
      significantly increased the time to first defecation (P = 0.045 vs vehicle
      treated rats), clearly suggesting a constipating effect of this drug. Although
      administration of ZnPPIX or hemin alone had no effect on this gastrointestinal
      motility parameter, ZnPPIX co-administered with granisetron abolished the
      granisetron-induced constipation. On the other hand, co-administration of hemin
      and granisetron did not modify the increased constipation observed under
      granisetron alone. When administered in vitro, granisetron alone (3 MUmol/L) did
      not significantly modify the colon's contractile response to either EFS or ACh.
      Incubation with ZnPPIX alone (10 MUmol/L) significantly reduced the colon's
      contractile response to EFS (P = 0.016) but had no effect on contractile response
      to ACh. Co-administration of ZnPPIX and atropine (3 MUmol/L) abolished the ZnPPIX
      mediated decrease in contractile response to EFS. Conversely, incubation with
      CORM-3 (400 MUmol/L) alone increased both the contractile response to EFS at 10
      Hz (10 Hz: 71.02 +/- 19.16 vs 116.25 +/- 53.70, P = 0.01) and the contractile
      response to ACh (100 MUmol/L) (P = 0.012). Co-administration of atropine
      abolished the CORM-3-mediated effects on the EFS-mediated response. When
      granisetron was co-incubated in vitro with ZnPPIX, the ZnPPIX-mediated decrease
      in colon contractile response to EFS was lost. On the other hand, co-incubation
      of granisetron and CORM-3 (400 MUmol/L) further increased the colon's contractile
      response to EFS (at 5 Hz: P = 0.007; at 10 Hz: P = 0.001) and to ACh (ACh 10
      MUmol/L: P = 0.001; ACh 100 MUmol/L: P = 0.001) elicited by CORM-3 alone. L-NNA
      co-administered with granisetron and CORM-3 abolished the potentiating effect of
      CORM-3 on granisetron on both the EFS-induced and ACh-induced contractile
      response. CONCLUSION: Taken together, findings from in vivo and in vitro studies
      suggest that the HO/CO pathway is involved in the constipating effects of
      granisetron.

PMID- 27895419
TI  - Acute kidney injury and post-reperfusion syndrome in liver transplantation.
AB  - In the past decades liver transplantation (LT) has become the treatment of choice
      for patients with end stage liver disease (ESLD). The chronic shortage of
      cadaveric organs for transplantation led to the utilization of a greater number
      of marginal donors such as older donors or donors after circulatory death (DCD).
      The improved survival of transplanted patients has increased the frequency of
      long-term complications, in particular chronic kidney disease (CKD). Acute kidney
      injury (AKI) post-LT has been recently recognized as an important risk factor for
      the occurrence of de novo CKD in the long-term outcome. The onset of AKI post-LT
      is multifactorial, with pre-LT risk factors involved, including higher Model for
      End-stage Liver Disease score, more sever ESLD and pre-existing renal
      dysfunction, either with intra-operative conditions, in particular ischaemia
      reperfusion injury responsible for post-reperfusion syndrome (PRS) that can
      influence recipient's morbidity and mortality. Post-reperfusion syndrome-induced
      AKI is an important complication post-LT that characterizes kidney involvement
      caused by PRS with mechanisms not clearly understood and implication on graft and
      patient survival. Since pre-LT risk factors may influence intra-operative events
      responsible for PRS-induced AKI, we aim to consider all the relevant aspects
      involved in PRS-induced AKI in the setting of LT and to identify all studies that
      better clarified the specific mechanisms linking PRS and AKI. A PubMed search was
      conducted using the terms liver transplantation AND acute kidney injury; liver
      transplantation AND post-reperfusion syndrome; acute kidney injury AND post
      reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five
      hundred seventy four articles were retrieved on PubMed search. Results were
      limited to title/abstract of English-language articles published between 2000 and
      2015. Twenty-three studies were identified that specifically evaluated incidence,
      risk factors and outcome for patients developing PRS-induced AKI in liver
      transplantation. In order to identify intra-operative risk factors/mechanisms
      specifically involved in PRS-induced AKI, avoiding confounding factors, we have
      limited our study to "acute kidney injury AND DCD AND liver transplantation".
      Accordingly, three out of five studies were selected for our purpose.

PMID- 27895422
TI  - Genetic polymorphism in CD14 gene, a co-receptor of TLR4 associated with non
      alcoholic fatty liver disease.
AB  - AIM: To evaluate the pathogenic role of toll-like receptor (TLR) gene
      polymorphisms in patients with non-alcoholic fatty liver disease (NAFLD).
      METHODS: Two hundred and fifty subjects (NAFLD = 200, healthy volunteers = 50)
      underwent polymerase chain reaction and restriction fragment length polymorphism
      to assess one polymorphism in the toll-like receptor 2 (TLR2) gene (A753G), two
      polymorphisms in the TLR4 gene (TLR4 Asp299Gly and Thr399Ile allele), and two
      polymorphisms in the cluster of differentiation 14 (CD14) (C-159T and C-550T)
      gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and
      its severity was evaluated by genetic models of association. RESULTS: On both
      multiplicative and recessive models of gene polymorphism association, there was
      significant association of CD14 C (-159) T polymorphism with NAFLD; patients with
      TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC
      genotype. There was no association of TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile,
      and CD14 C (-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms
      had an association with histological severity of NAFLD. CONCLUSION: Patients with
      CD14 C (-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk
      of NAFLD development.

PMID- 27895424
TI  - IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitis
      in vitro.
AB  - AIM: To investigate the role of interferon regulatory factor 5 (IRF5) in
      reversing polarization of lung macrophages during severe acute pancreatitis (SAP)
      in vitro. METHODS: A mouse SAP model was established by intraperitoneal (ip)
      injections of 20 MUg/kg body weight caerulein. Pathological changes in the lung
      were observed by hematoxylin and eosin staining. Lung macrophages were isolated
      from bronchoalveolar lavage fluid. The quantity and purity of lung macrophages
      were detected by fluorescence-activated cell sorting and evaluated by real-time
      polymerase chain reaction (RT-PCR). They were treated with IL-4/IRF5 specific
      siRNA (IRF5 siRNA) to reverse their polarization and were evaluated by detecting
      markers expression of M1/M2 using RT-PCR. RESULTS: SAP associated acute lung
      injury (ALI) was induced successfully by ip injections of caerulein, which was
      confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1
      phenotype during the early acute pancreatitis stages. Reduction of IRF5
      expression by IRF5 siRNA reversed the action of macrophages from M1 to M2
      phenotype in vitro. The expressions of M1 markers, including IRF5 (S + IRF5 siRNA
      vs S + PBS, 0.013 +/- 0.01 vs 0.054 +/- 0.047, P < 0.01), TNF-alpha (S + IRF5
      siRNA vs S + PBS, 0.0003 +/- 0.0002 vs 0.019 +/- 0.018, P < 0.001), iNOS (S +
      IRF5 siRNA vs S + PBS, 0.0003 +/- 0.0002 vs 0.026 +/- 0.018, P < 0.001) and IL-12
      (S + IRF5 siRNA vs S + PBS, 0.000005 +/- 0.00004 vs 0.024 +/- 0.016, P < 0.001),
      were decreased. In contrast, the expressions of M2 markers, including IL-10 (S +
      IRF5 siRNA vs S + PBS, 0.060 +/- 0.055 vs 0.0230 +/- 0.018, P < 0.01) and Arg-1
      (S + IRF5 siRNA vs S + PBS, 0.910 +/- 0.788 vs 0.0036 +/- 0.0025, P < 0.001),
      were increased. IRF5 siRNA could reverse the lung macrophage polarization more
      effectively than IL-4. CONCLUSION: Treatment with IRF5 siRNA can reverse the
      pancreatitis-induced activation of lung macrophages from M1 phenotype to M2
      phenotype in SAP associated with ALI.

PMID- 27895423
TI  - Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells
      in colitis mice.
AB  - AIM: To investigate the role of regulatory T cell (Treg) subsets in the balance
      between Treg and T helper 17 (Th17) cells in various tissues from mice with
      dextran sulfate sodium-induced colitis. METHODS: Treg cells, Treg cell subsets,
      Th17 cells, and CD4+CD25+FoxP3+IL-17+ cells from the lamina propria of colon
      (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow
      cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC
      mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL
      17A levels were detected with a Cytometric Beads Array. RESULTS: In peripheral
      blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum
      (LPJ) and LPC from UC mice, Treg cell numbers were increased (P < 0.05), and
      FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased
      in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI
      subset cells (CD4+CD45RA+FoxP3low) was increased in the spleen, MLN, LPJ, and
      LPC. FrII subset cells (CD4+CD45RA-FoxP3high) were decreased among PBMC, MLN,
      LPJ, and LPC, but the number of FrIII cells (CD4+CD45RA-FoxP3low) and
      CD4+CD25+FoxP3+IL-17A+ cells was increased. FoxP3 mRNA levels in CD4+CD45RA
      FoxP3low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and
      RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA
      FoxP3high, and CD4+CD45RA-FoxP3low cells was higher in LPC relative to other
      tissues. CONCLUSION: Increased numbers of CD4+CD45RA-FoxP3low cells may cause an
      imbalance between Treg and Th17 cells that is mainly localized to the LPC rather
      than secondary lymphoid tissues.

PMID- 27895426
TI  - Influence of night duty on endoscopic therapy for bile duct stones.
AB  - AIM: To examine the influence of night duty (ND) on endoscopic therapy for
      biliary duct stones. METHODS: The subjects consisted of 133 patients who received
      initial endoscopic therapy for biliary duct stones performed by eight
      endoscopists after they had been on (ND group, n = 34 patients) or not [day duty
      (DD) group, n = 99 patients]. Patient characteristics (age, gender, history of
      abdominal surgery, transverse diameter of the largest stone, number of stones),
      years of experience of the endoscopists, endoscopic procedures [sphincterotomy,
      papillary balloon dilation (EPBD), papillary large balloon dilation (EPLBD)], and
      outcomes of initial endoscopy (procedure time; rate of stone removal by the first
      endoscopist; procedure success rate by the first endoscopist: removal of stones
      or endoscopic retrograde biliary drainage; rate of final stone removal; final
      procedure success rate; complications; hospitalization after the procedure) were
      compared retrospectively between the two groups. History of abdominal surgery and
      treatment outcomes were also compared between the groups for each of the four
      endoscopists who performed most of the procedures in the ND group. RESULTS: There
      were no significant differences regarding the number of treatments performed by
      each endoscopist or the years of experience between the ND and DD groups. The
      frequency of endoscopic retrograde cholangiopancreatography procedures did not
      differ significantly between the groups. There were also no significant
      differences regarding patient characteristics: age, gender, history of abdominal
      surgery (ND 7: Billroth II 4, R-Y 3; DD 18: double tract reconstruction 1,
      Billroth I 3, Billroth II 6, R-Y 7, duodenoduodenostomy for annular pancreas 1),
      transverse diameter of largest stone, and number of stones between the two
      groups. Among the treatment procedures, the endoscopic sphincterotomy and EPBD
      rates did not differ significantly between the groups. However, EPLBD was
      performed more frequently in the ND group [47.1% (16/34) vs 19.2% (19/99)].
      Regarding outcomes, there were no significant differences in the rate of stone
      removal, procedure success rate, complications (ND: pancreatitis 1; DD:
      pancreatitis 6, duodenal bleeding 1, decreased blood pressure 1, hypoxia 2), or
      hospitalization after the procedure. However, the procedure time was
      significantly longer in the ND group (71.5 +/- 44.7 vs 54.2 +/- 28.8). Among the
      four endoscopists, there were no significant differences in patient history of
      abdominal surgery, removal of stones, or procedure success rate. However, the
      procedure time for one endoscopist was significantly longer in the ND group.
      CONCLUSION: The time required for endoscopic therapy for bile duct stones might
      be influenced by ND.

PMID- 27895425
TI  - Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and
      efficacy.
AB  - AIM: To study the tolerance and the efficiency of FOLFIRINOX in elderly patients
      diagnosed with colorectal or pancreatic cancer. METHODS: This retrospective study
      included elderly patients aged over 70 years of age treated at Georges-Francois
      Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic
      cancer between January 2009 and January 2015. Chemotheapy regimen consisted of
      oxaliplatin (85 mg/m2 in over 120 min) followed by leucovorin (400 mg/m2 in over
      120 min), with the addition, after 30 min of irinotecan (180 mg/m2 in over 90
      min) then 5 fluorouracil (5FU) (400 mg/m2 administred intravenous bolus),
      followed by 5FU (2400 mg/m2 intraveinous infusion over 46 h) repeated every 2 wk.
      Geriatric parameters were recorded at the beginning. Toxicities were evaluated
      with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was
      evaluated by CT scan. Treatment continued until disease progression, unacceptable
      toxicities or patient refusal. RESULTS: Fifty-two patients aged from 70 to 87
      years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic
      cancer. Most of them were in good general condition, 82.7% had a 0-1 performance
      status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe
      toxicities were neutropenia (17 patients, n = 32.7%) and diarrhea (35 patients n
      = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4
      toxicity. Thirty-nine patients (75%) initially received an adapted dose of
      chemotherapy. The dosage was adjusted for 26% of patients during the course of
      treatment. Tumor response evaluated by RECIST criteria showed a controlled
      disease for 25 patients (48.1%), a stable disease for 13 and a partial response
      for 12 patients. Time under treatment was higher for colorectal cancer with a
      median time of 2.44 mo (95%CI: 1.61-3.25). Overall survival was 43.88 mo for
      colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or
      multivariate analysis, none of geriatric parameters were linked to overall
      survival. Only the type of tumor (pancreatic/colorectal) was linked in both
      analysis. CONCLUSION: For people over 70 years old, FOLFIRINOX regimen seems to
      induce manageable toxicities but similar, even higher, median survival rates
      compared to younger people.

PMID- 27895427
TI  - Irritable bowel syndrome evaluation using computed tomography colonography.
AB  - AIM: To evaluate the morphology of the colon in patients with irritable bowel
      syndrome (IBS) by using computed tomography colonography (CTC). METHODS: Twelve
      patients with diarrhea type IBS (IBS-D), 13 patients with constipation type IBS
      (IBS-C), 12 patients with functional constipation (FC) and 14 control patients
      underwent colonoscopy following CTC. The lengths of the rectosigmoid colon,
      transverse colon and the total colon were measured. The diameters of the rectum,
      sigmoid colon, descending colon, transverse colon, and ascending colon were
      measured. RESULTS: The mean length of the total colon was 156.5 cm in group C,
      158.9 cm in group IBS-D, 172.0 cm in group IBS-C, and 188.8 cm in group FC. The
      total colon in group FC was significantly longer than that in group C (P < 0.05).
      The mean length of the rectosigmoid colon was 56.2 cm, 55.9 cm, 63.6cm, and 77.4
      cm (NS). The mean length of the transverse colon was 49.9 cm, 43.1 cm, 57.0 cm,
      and 55.0 cm. The transverse colon in group IBS-D was significantly shorter than
      that in group IBS-C (P < 0.01) and that in group FC (P = 0.02). The mean diameter
      of the sigmoid colon was 4.0 cm, 3.3 cm, 4.2 cm, and 4.3 cm (NS). The mean
      diameter of the descending colon was 3.6 cm, 3.1 cm, 3.8 cm, and 4.3 cm. The
      descending colon diameter in group IBS-D was significantly less than that in
      group IBS-C (P = 0.03) and that in group FC (P < 0.001). The descending colon
      diameter in group FC was significantly greater than that in group C (P = 0.04).
      The mean diameter of the transverse colon was 4.4 cm, 3.3 cm, 4.2 cm, and 5.0 cm
      (NS). CONCLUSION: CT colonography might contribute the clarification of subtypes
      of IBS.

PMID- 27895429
TI  - Potential model for differential diagnosis between Crohn's disease and primary
      intestinal lymphoma.
AB  - AIM: To evaluate the usefulness of different parameters to differentiate Crohn's
      disease (CD) from primary intestinal lymphoma (PIL). METHODS: The medical records
      of 85 patients with CD and 56 patients with PIL were reviewed retrospectively.
      Demographic, clinical, laboratory, endoscopic, and computed tomographic
      enterography (CTE) parameters were collected. The univariate value of each
      parameter was analyzed. A differentiation model was established by pooling all
      the valuable parameters. Diagnostic efficacy was analyzed, and a receiver
      operating characteristic (ROC) curve was plotted. RESULTS: The demographic and
      clinical parameters that showed significant values for differentiating CD from
      PIL included age of onset, symptom duration, presence of diarrhea, abdominal
      mass, and perianal lesions (P < 0.05). Elevated lactate dehydrogenase and serum
      beta2-microglobulin levels suggested a PIL diagnosis (P < 0.05). The endoscopic
      parameters that showed significant values for differentiating CD from PIL
      included multiple-site lesions, longitudinal ulcer, irregular ulcer, and
      intraluminal proliferative mass (P < 0.05). The CTE parameters that were useful
      in the identification of the two conditions included involvement of <= 3
      segments, circular thickening of the bowel wall, wall thickness > 8 mm,
      aneurysmal dilation, stricture with proximal dilation, "comb sign", mass showing
      the "sandwich sign", and intussusceptions (P < 0.05). The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of the differentiation model were 91.8%, 96.4%, 93.6%, 97.5%, and 88.5%,
      respectively. The cutoff value was 0.5. The area under the ROC curve was 0.989.
      CONCLUSION: The differentiation model that integrated the various parameters
      together may yield a high diagnostic efficacy in the differential diagnosis
      between CD and PIL.

PMID- 27895430
TI  - Full-thickness myotomy is associated with higher rate of postoperative
      gastroesophageal reflux disease.
AB  - AIM: To compare long-term occurrence of gastroesophageal reflux disease (GERD)
      between two different types of peroral endoscopic myotomy (POEM) for achalasia.
      METHODS: We included all patients with achalasia who underwent POEM at our
      hospital from August 2011 to October 2012 and had complete GERD evaluation with
      >= 3 years of follow-up. They were divided into circular or full-thickness
      myotomy groups according to the depth of myotomy. Demographics, Eckardt score,
      manometry results, 24-h pH monitoring, and GERD symptoms were recorded and
      compared between the two groups. RESULTS: We studied 56 patients (32 circular
      myotomy and 24 full-thickness myotomy) with complete GERD evaluation. There was
      no significant difference between the two groups in terms of treatment success
      (defined as Eckardt score <= 3), postoperative Eckardt score, mean basal lower
      esophageal sphincter pressure, and 4-s integrated relaxation pressure (4sIRP).
      Postoperative abnormal esophageal acid exposure was found in 25 patients (44.6%).
      A total of 13 patients (23.2%) had GERD symptoms and 12 had esophagitis (21.4%).
      Clinically relevant GERD (abnormal esophageal acid exposure associated with GERD
      symptoms and/or esophagitis) was diagnosed in 13 patients (23.2%). Multivariate
      analysis revealed that full-thickness myotomy and low level of postoperative
      4sIRP were predictive factors for clinically relevant GERD. CONCLUSION: Efficacy
      and manometry are comparable between achalasia patients treated with circular or
      full-thickness myotomy. But patients with full-thickness myotomy and low
      postoperative 4sIRP have more GERD.

PMID- 27895428
TI  - Lymphovascular invasion in more than one-quarter of small rectal neuroendocrine
      tumors.
AB  - AIM: To identify the frequency, clinicopathological risk factors, and prognostic
      significance of lymphovascular invasion (LVI) in endoscopically resected small
      rectal neuroendocrine tumors (NETs). METHODS: Between June 2005 and December
      2015, 104 cases of endoscopically resected small (<= 1 cm) rectal NET specimens
      at Hallym University Sacred Heart Hospital in Korea were retrospectively
      evaluated. We compared the detected rate of LVI in small rectal NET specimens by
      two methods: hematoxylin and eosin (H&E) and ancillary immunohistochemical
      staining (D2-40 and Elastica van Gieson); in addition, LVI detection rate
      difference between endoscopic procedures were also evaluated. Patient
      characteristics, prognosis and endoscopic resection results were reviewed by
      medical charts. RESULTS: We observed LVI rates of 25.0% and 27.9% through H&E and
      ancillary immunohistochemical staining. The concordance rate between H&E and
      ancillary studies was 81.7% for detection of LVI, which showed statistically
      strong agreement between two methods (kappa = 0.531, P < 0.001). Two endoscopic
      methods were studied, including endoscopic submucosal resection with a ligation
      device and endoscopic submucosal dissection, and no statistically significant
      difference in the LVI detection rate was detected between the two (26.3% and
      26.8%, P = 0.955). LVI was associated with large tumor size (> 5 mm, P = 0.007),
      tumor grade 2 (P = 0.006). Among those factors, tumor grade 2 was the only
      independent predictive factor for the presence of LVI (HR = 4.195, 95%CI: 1.321
      12.692, P = 0.015). No recurrence was observed over 28.8 mo regardless of the
      presence of LVI. CONCLUSION: LVI may be present in a high percentage of small
      rectal NETs, which may not be associated with short-term prognosis.

PMID- 27895431
TI  - Occult hepatitis B virus infection is not associated with disease progression of
      chronic hepatitis C virus infection.
AB  - AIM: To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI)
      and the association between OBI and liver disease progression, defined as
      development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of
      Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV)
      infection. METHODS: This prospective cohort study enrolled 174 patients with
      chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n =
      44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI
      was defined as HBV DNA positivity in 2 or more different viral genomic regions by
      nested polymerase chain reaction using 4 sets of primers in the S, C, P and X
      open reading frame of the HBV genome. RESULTS: The overall OBI prevalence in
      chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the
      chronic hepatitis C, liver cirrhosis and HCC groups, respectively (P = 0.845).
      During follow-up, 52 patients showed disease progression, which was independently
      associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and
      sustained virologic response (SVR), but not with OBI positivity. In 136 patients
      who were not in the SVR state during the study period, OBI positivity was
      associated with neither disease progression, nor HCC development. CONCLUSION: The
      prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated
      with disease progression in South Koreans.

PMID- 27895432
TI  - Prevalence of depression and anxiety in patients with chronic digestive system
      diseases: A multicenter epidemiological study.
AB  - AIM: To investigate the prevalence of depression and anxiety in patients with
      chronic digestive system diseases. METHODS: A total of 1736 patients with chronic
      digestive system diseases were included in this cross-sectional study, including
      871 outpatients and 865 in-patients. A self-designed General Information for
      Patients of the Department of Gastroenterology of General Hospitals questionnaire
      was used to collect each patient's general information, which included
      demographic data (including age, sex, marital status, and education) and disease
      characteristics (including major diseases, disease duration, principal symptoms,
      chronic pain, sleep disorder, and limited daily activities). RESULTS: The overall
      detection rate was 31.11% (540/1736) for depression symptoms alone, 27.02%
      (469/1736) for anxiety symptoms alone, 20.68% (359/1736) for both depression and
      anxiety symptoms, and 37.44% (650/1736) for either depression or anxiety
      symptoms. Subjects aged 70 years or above had the highest detection rate of
      depression (44.06%) and anxiety symptoms (33.33%). chi2 trend test showed: the
      higher the body mass index (BMI), the lower the detection rate of depression and
      anxiety symptoms (chi2trend = 13.697, P < 0.001; chi2trend = 9.082, P = 0.003);
      the more severe the limited daily activities, the higher the detection rate of
      depression and anxiety symptoms (chi2trend = 130.455, P < 0.001, chi2trend =
      108.528, P < 0.001); and the poorer the sleep quality, the higher the detection
      rate of depression and anxiety symptoms (chi2trend = 85.759, P < 0.001; chi2trend
      = 51.969, P < 0.001). Patients with digestive system tumors had the highest
      detection rate of depression (57.55%) and anxiety (55.19%), followed by patients
      with liver cirrhosis (41.35% and 48.08%). Depression and anxiety symptoms were
      also high in subjects with comorbid hypertension and coronary heart disease.
      CONCLUSION: Depression and anxiety occur in patients with tumors, liver
      cirrhosis, functional dyspepsia, and chronic viral hepatitis. Elderly,
      divorced/widowed, poor sleep quality, and lower BMI are associated with higher
      risk of depression and anxiety.

PMID- 27895434
TI  - BAY 41-2272 Treatment Improves Acetylcholine-Induced Aortic Relaxation in L-NAME
      Hypertensive Rats.
AB  - Hypertension, an emerging problem of recent era, and many pathophysiological
      factors are participating to produce the disease. Nitric oxide (NO) is an
      important constituent to ameliorate hypertensive condition. Inhibition of
      endogenous NO synthase by L-NG-Nitroarginine methyl ester (L-NAME) was
      responsible for generating hypertension in rats. BAY 41-2272 (5-cyclopropyl-2-[1
      (2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine), a
      soluble guanylyl cyclase activator, restricts rise of blood pressure and shows
      cardioprotective activity. The aim of the present study was to analyze effect of
      short-term BAY 41-2272 treatment on blood pressure and vascular function. Male
      Wistar rats were randomly divided into three groups such as control (group-A),
      hypertensive (group-B), and BAY 41-2272-treated hypertensive (group-C) rats.
      Normal saline was administered intramuscularly to control rats for last 3 days
      (days 40, 41, and 42) of total 42 days treatment, whereas rats of group-B and
      group-C were treated with L-NAME hydrochloride in drinking water at 50 mg/kg body
      weight daily for 42 days. Also, normal saline and BAY 41-2272 were administered
      for last 3 days at two different dosages at 1 and 3 mg/kg body weight/day
      intramuscularly to group-B and group-C rats, respectively. Administration of BAY
      41-2272 for 3 days was not sufficient enough to decrease mean arterial pressure
      of hypertensive rats significantly. BAY at both the treatment dosages
      significantly ameliorate acetylcholine-induced maximal aortic relaxation compared
      with BAY-untreated hypertensive rats. Findings of the present study indicate that
      even shorter period of BAY 41-2272 treatment (3 days) improves vascular
      relaxation.

PMID- 27895433
TI  - Complete response with sorafenib and transcatheter arterial chemoembolization in
      unresectable hepatocellular carcinoma.
AB  - Patients with advanced hepatocellular carcinoma (HCC) showing portal vein tumor
      thrombosis (PVTT) have an extremely poor prognosis. According to treatment
      guidelines, the only option for HCC patients with PVTT is sorafenib chemotherapy.
      However, in Asia, various treatments have been attempted and possible
      prolongation of overall survival has been repeatedly reported. We herein report
      the first case of a patient with an initially unresectable advanced HCC with PVTT
      who underwent curative hepatectomy after sorafenib and transcatheter arterial
      chemoembolization (TACE) showing complete histological response. Two months after
      induction with sorafenib, a significant decrease in serum alpha-fetoprotein level
      was observed and computed tomography imaging showed a significant decrease in
      tumor size. Because of remaining PVTT, TACE and curative resection were
      performed. The combination of sorafenib and TACE may be an effective treatment
      for HCC patients with PVTT.

PMID- 27895435
TI  - Optimal MRI interval for detection of asymptomatic recurrence in surgically
      treated early cervical cancer by use of a mathematical model.
AB  - INTRODUCTION: Applications of mathematical modeling may provide an insight into
      the timing of surveillance modalities. We aimed to determine the optimal magnetic
      resonance imaging (MRI) interval for the detection of surgically treated early
      cervical cancer asymptomatic recurrence by using a mathematical model for
      volumetric tumor growth time. METHODS: We assumed that tumor volume increases by
      a factor equal to the basis of natural logarithms (e~2.718) at constant time
      intervals. Using a mathematical formula, the tumor volume (V) was converted to
      diameter (D), which could be expressed as a function of time (t), given an
      initial diameter Di (corresponding to initial volume Vi) and a constant DT, where
      DT is the time required for volumetric tumor growth by a factor (e). Three
      different DTs were used for demonstration of the model, i.e. 20, 100 and 400
      days. RESULTS: Assuming complete surgical clearance, a worst-case scenario for a
      20-day DT indicated that a 20 MUm cervical tumor would need at least 12 months to
      reach 10 mm in diameter, which would be detected with an annual surveillance
      interval MRI. Over a 5-year (60 months) follow-up, nearly five surveillance MRIs
      would be required if the threshold of 10 mm was desired. For a 100-day DT over a
      5-year (60 months) follow-up, a single only MRI would be required, if the
      threshold of 10 mm was desired. In the case of an indolent tumor (DT is 400
      days), the model would not recommend a surveillance MRI to detect asymptomatic
      recurrence. A positive linear association between optimal MRI intervals and
      volumetric tumor DTs was demonstrated. CONCLUSION: In the absence of evidence, we
      postulate annual MRI scanning is probably the shortest interval, which can be
      clinically useful for optimization of routine surveillance follow-up protocols in
      surgically treated early cervical cancer. This mathematical model requires proper
      verification in prospective clinical studies. Hippokratia 2016, 20(1): 4-8.

PMID- 27895436
TI  - Rising incidence of thyroid cancer in Serbia.
AB  - BACKGROUND: In the past decade, the incidence of thyroid cancer (TC) has shown a
      stable increase, for both sexes, in many parts of the world at a rate faster than
      for any other type of malignancy. The aim of our study was to analyze and report
      changes in TC incidence in Serbia, as well as to evaluate potential reasons for
      these changes. So far, the incidence of TC in Serbia has not been reported.
      MATERIAL AND METHODS: This is a retrospective descriptive epidemiological study
      of TC data from the Cancer Register for Serbia for a ten year period, from 1999
      to 2008. Crude rates (CR), age-specific rates (ASR), age-adjusted rates (AAR),
      linear trends and average annual percentage changes (AAPC) were calculated and
      analyzed. RESULTS: TC incidence increased substantially for both genders with the
      highest increase in 2007 for the age group 50-59 (females 14.2, males 10.3). TC
      was three times more common in females (CR 4.7:1.5). The AAR for females ranged
      1.9-4.8 (3.3, 95% CI 2.6-4.0), for males 1.0-2.6 (1.0, 95% CI 0.8-1.2) and for
      both sexes combined 1.4-3.2 (2.2, 95% CI 1.7-2.6). The incidence trend for males
      showed an increase (y =0.05x + 0.70, p =0.058). It was highly statistically
      significant for females (y =0.31x + 1.61, p <0.001) and both genders combined (y
      =0.18x + 1.18, p <0.001). AAPC was highest for ages 20-29 and 30-39, for females
      (+25.2%) and males (+17.3%), respectively. CONCLUSIONS: We found a substantial
      increase in TC incidence in Serbia for both genders. The highest increase in TC
      incidence was found in females aged 20 to 29 years while the highest incidence
      was found in the age group 50 to 59.

PMID- 27895437
TI  - Isotretinoin increased carotid intima-media thickness in acne patients.
AB  - BACKGROUND: Isotretinoin (Iso) in acne treatment may cause dyslipidemia and
      increase in liver enzymes. Moreover, its effect on lipid and glucose metabolism
      may induce atherosclerotic complications. The aim of this study was to evaluate
      carotid intima-media thickness (CIMT), osteopontin (OPN), lipid, high sensitive C
      reaktive protein (hs-CRP) levels, and insulin resistance (HOMA-IR) in acne
      patients before and after Iso treatment. MATERIALS: Twenty-one acne patients were
      treated with Iso (0.5-0.8 mg/kg) for four months. Blood tests for lipid profile,
      fasting glucose, liver enzymes, OPN, HOMA-IR, hs-CRP and CIMT measurements were
      performed before and after Iso treatment. Serum levels of OPN and, hs-CRP were
      measured by ELISA and particle-enhanced turbidimetric immunoassay respectively.
      RESULTS: Iso treatment significantly increased lipid levels, CIMT (0.60-0.74 mm;
      p ?0.001); whereas it non-significantly increased HOMA-IR (0.91-1.87; p =0.70),
      OPN (4.32-5.44 ng/ml; p =0.27), and hs-CRP (0.08-0.09 mg/dl; p =0.88) levels.
      There was no correlation between OPN and CIMT (p =0.77). CONCLUSION: Isotretinoin
      treatment for four months significantly increased CIMT in acne patients.
      Hippokratia 2016, 20(1): 14-18.

PMID- 27895438
TI  - The quality of death certification practice in Greece.
AB  - BACKGROUND: Death certification represents an excellent source for mortality
      statistics and appropriate public health surveillance. Errors in reporting the
      cause of death impede the development of national health policies and,
      accordingly, allocation of resources. The aim of this study was to determine the
      frequency of errors in the cause of death and to identify factors that may be
      associated with inaccuracies in death certificates. METHODS: A cross-sectional
      study of all natural death certifications in a defined Greek region was conducted
      over the period 2006-2010. Specific criteria for major and minor errors were
      adopted for the evaluation of death certificates. RESULTS: A total of 5,828 death
      certificates due to natural causes were identified. Major errors were found in
      64.6 % of them with almost every death certificate having a minor error. Major
      error rate did not differ per year (p =0.65). Most commonly encountered major
      errors were a non-acceptable cause of death (31.2 %) and an incorrect sequencing
      (16.8 %). Factors affecting their frequency were the age of the deceased (older
      than 80 years, p =0.025), the area of certificate completion (rural and semi
      urban, p <0.001) and doctor's grade (consultant, p <0.026). CONCLUSIONS: High
      rate of recording errors at death certification influences the accuracy of the
      cause of death in a defined region in Southern Greece. Due to their impact on
      mortality statistics and health policies, standard practices of death
      certification should be established. Coordinated educational interventions are
      expected to play a significant role on this. Hippokratia 2016, 20(1): 19-25.

PMID- 27895440
TI  - Is there a direct correlation between the duration and the treatment of type 2
      diabetes mellitus and hearing loss?
AB  - AIM: The aim of the study was to determine the impact of the duration of diabetes
      and the control of glycemia on the auditory function of patients with type 2
      diabetes mellitus (T2DM). MATERIALS AND METHODS: This prospective study included
      80 patients with T2DM (divided depending on when T2DM was diagnosed, and also
      according to the control of glycemia), and 50 healthy subjects. RESULTS: The
      hearing threshold in T2DM patients was statistically significantly higher for
      1,000 Hz, 2,000 Hz, 4,000 Hz and 8,000 Hz. Absolute latencies of brainstem
      auditory evoked potentials (BAEP) revealed significant differences between
      average absolute latencies for waves I, III and V, as well as inter-wave
      latencies I-V and I-III (p <0.001). A statistically significant difference was
      noted in the presence of transitory otoacoustic emissions (TEOAE) (p <0.001). In
      T2DM patients with poor glycemic control, where the glycated hemoglobin (HbA1c)
      is above 7%, the hearing threshold levels were statistically significantly higher
      in both ears at 8,000 Hz and at 2,000 Hz in the right ear, and the absolute
      latency of wave V was prolonged in the right ear. There was no evidence that the
      duration of diabetes significantly affected the auditory threshold, absolute and
      inter-wave BAEP latencies. CONCLUSION: The patients with T2DM displayed an
      increased hearing threshold, qualitative changes in BAEP and the absence of
      TEOAE. The duration of poorly-controlled glycemia had a greater effect on the
      patients' auditory function than the duration of T2DM. Hippokratia 2016, 20(1):
      32-37.

PMID- 27895439
TI  - Comparison of two different molecular weight intra-articular injections of
      hyaluronic acid for the treatment of knee osteoarthritis.
AB  - BACKGROUND: Knee osteoarthritis (OA) is an incurable joint disorder, representing
      a major public health issue. Among options for symptom control,
      viscosupplementation with hyaluronic acid (HA) had established usefulness in pain
      and function improvement of the knee. However, it is not clear which form of HA
      yields better results. MATERIAL AND METHODS: We compared two HA preparations with
      high (HMW) or low molecular weight (LMW) in terms of pain control and function
      improvement using the Western Ontario and McMaster Universities Osteoarthritis
      Index (WOMAC) and the visual analog scale (VAS) score in patients with knee OA.
      During 2013, 80 patients were enrolled in this prospective, double-blind,
      randomized study. Each patient received a weekly injection of either preparation
      with a total of five injections for the LMW group and three for the HMW group.
      They were evaluated at baseline, five weeks, three months and one year after
      treatment. RESULTS: In both groups, HA treatment resulted in significant
      improvement in pain and function that begun immediately after treatment and
      lasted for one year. However when compared with each other, HMW and LMW groups
      were comparable in mean WOMAC, and VAS score at each time point. Neither
      preparation can interrupt disease progression as radiological findings remained
      constant during follow-up. CONCLUSIONS: Intra-articular injections using HMW or
      LMW HA can improve stiffness, joint function and pain in patients suffering from
      knee OA. However, no clear benefit seems to exist between the two preparations
      and neither can slow disease progression. Hippokratia 2016, 20(1): 26-31.

PMID- 27895442
TI  - Translation of the Medical Fear Survey to Serbian: psychometric properties.
AB  - BACKGROUND: Medical Fear Survey (MFS) is an instrument designed for measuring
      fear of medical and related treatments. OBJECTIVE: Aim of the present study was
      MFS translation into Serbian, measurement of its psychometric properties and MFS
      validation using other Blood-injury-injections and related stimuli instruments
      that have been translated from English into Serbian. METHOD: After obtaining
      permission from the author of the original MFS, double forward translation from
      English to Serbian and backward translation to English were conducted in ten
      steps, according to International Society for Pharmacoeconomics and Outcomes
      Research (ISPOR) guidelines. Reliability, factorial analysis and concurrent
      validation of Serbian version of MFS were conducted on a sample of 485 medical or
      pharmacy students at University of Kragujevac, Serbia. RESULTS: Serbian version
      of MFS showed high internal consistency with a Cronbach's alpha 0.968 and good
      temporal stability after testing-and-retesting (Spearman's correlation
      coefficient 0.838, and intraclass correlation coefficient 0.877). Factorial
      analysis confirmed the same five factors demonstrated in the original English
      version: fear of mutilated bodies (10 items), fear of blood (11 items), fear of
      injections and blood draws (9 items), fear of sharp objects (10 items), and fear
      of medical examinations and physical symptoms (10 items). The total score of MFS
      correlated significantly with the total scores of Injection Phobia Scale-Anxiety
      (Spearman's correlation coefficient 0.391, p <0.001), Blood/Injection Fear Scale
      (Spearman's correlation coefficient 0.502, p <0.001) and Medical Avoidance Survey
      (Spearman's correlation coefficient 0.396, p <0.001). CONCLUSIONS: Serbian
      version of the 50-item MFS showed similar psychometric properties as the original
      English version of this scale, with the same factorial structure. It could be
      used for measurement of fear of medical and related treatments in Serbian socio
      cultural milieu, preferably self-administered. Hippokratia 2016, 20(1): 44-49.

PMID- 27895441
TI  - A retrospective analysis of postoperative patients admitted to the intensive care
      unit.
AB  - BACKGROUND: The aim of this retrospective study was to evaluate postoperative
      patients admitted to the intensive care unit (ICU) and to describe their
      characteristics and outcomes. METHODS: We performed a retrospective chart review
      of 1,756 postoperative patients admitted to the ICU of a tertiary referral
      hospital from January 2008 to December 2012. For each patient we recorded:
      demographic data, reason for admission to the ICU, duration of mechanical
      ventilation, elective versus emergency surgery, type of anaesthesia, American
      Society of Anesthesiologists (ASA) physical status, Acute Physiology and Chronic
      Health Evaluation (APACHE) II score, Glasgow Coma Score (GCS), and outcome.
      RESULTS: During the study period, the rate of postoperative ICU admission
      increased each year, and the number of ICU beds was increased in order to perform
      a greater number of elective surgical procedures for patients who required
      postoperative ICU care. In 2008, 20.80 % of the patients were postoperatively
      admitted to the ICU; 58.97 % were in 2012. The mean ratio of five years was 46.97
      %. Median age was 63 (1-94) years, and 57.4 % of the patients were male. The most
      common reasons for admission were major surgery (41.90 %) and comorbidities
      (34.10 %). Mortality rates were higher in patients that underwent emergency
      surgery, received general anesthesia, were operated on by a general surgeon, or
      had low GCS scores coupled with high ASA or APACHE II scores. CONCLUSIONS: The
      postoperative patients who had metabolic or hemodynamic instability, high ASA or
      APACHE II scores, and low GCS had higher mortality rates despite ICU care.
      Hippokratia 2016, 20(1): 38-43.

PMID- 27895443
TI  - The validation and inter-rater reliability of the Serbian translation of the
      Richmond agitation and sedation scale in post anesthesia care unit patients.
AB  - BACKGROUND: Targeted light sedation is recommended because it shortens the time
      of mechanical ventilation and the length of stay in an intensive care unit (ICU).
      However, there is no validated scale for sedation and agitation in ICU in the
      Serbian speaking area. The aim of the current study was to validate, verify the
      reliability and enable the application of the Richmond Agitation and Sedation
      Scale (RASS) in the Serbian speaking area. METHODS: In this prospective cohort
      study, RASS was applied to 301 adult patients hospitalized in surgical ICUs by
      two different research team members. We tested RASS for inter-rater reliability
      by the correlation between them. The scale was validated by comparison to Glasgow
      Coma Scale (GCS) scores which was applied by the third investigator. Interrater
      agreement was measured using weighted kappa (k) and for correlation Spearman's
      test was used. RESULTS: The inter-rater reliability of the scale was high (k
      ?0.7). The degree of correlation between the RASS and the GCS during all five
      days of observation was high (?0.7 for both investigators, the fifth day). In all
      the cases, Spearman's correlation coefficient was highly significant (p ?0.01).
      CONCLUSIONS: The Serbian translation of the RASS is a reliable and valid
      instrument for the assessment of the levels of sedation and agitation with
      patients in ICU. Hippokratia 2016, 20(1): 50-54.

PMID- 27895444
TI  - Relationship of hemoxygenase-1 and prolidase enzyme activity with oxidative
      stress in papillary thyroid cancer.
AB  - AIM: Recent studies associate thyroid cancer with oxidative stress. We aim to
      clarify the relation between papillary thyroid cancer, oxidative stress,
      hemoxygenase-1, prolidase enzymes and investigate the availability of these
      enzymes as markers for diagnosis, success of treatment, and follow-up. METHODS:
      Thirty-one patients with papillary thyroid carcinoma and 25 healthy control
      subjects were included in this study. Hemoxygenase-1, prolidase (oxidant stress
      indicator), malondialdehyde, protein carbonyl, and superoxide dismutase (an
      indicator of antioxidant defense system) were measured pre-operatively and 30
      days after thyroidectomy. RESULTS: There was a significant decrease in serum
      levels of malondialdehyde and superoxide dismutase (p <0.001 for both) after
      thyroidectomy in papillary thyroid carcinoma group. In addition, there was a
      significant difference in the postoperative serum levels of prolidase,
      malondialdehyde, protein carbonyl, and superoxide dismutase between papillary
      thyroid carcinoma and control groups (p =0.024, p <0.001, p =0.002, and p =0.016,
      respectively) beside significant difference of malondialdehyde, protein carbonyl,
      hemoxygenase-1, and superoxide dismutase pre-operative serum levels (p <0.001, p
      =0.003, p =0.006, and p =0.025, respectively). CONCLUSION: When the
      unquestionable role of oxidative stress in the pathogenesis of cancer is
      considered, in the future it is expected to associate parametric changes in the
      serum of patients caused by oxidative stress to papillary thyroid cancer.
      Hippokratia 2016, 20(1): 55-59.

PMID- 27895445
TI  - Amblyopic-related frontal changes in an orientation discrimination task: a
      research of P3a event-related potentials in anisometropic amblyopia.
AB  - BACKGROUND: Amblyopic deficits in the primary and secondary visual cortex have
      been demonstrated broadly. However, the cognitive process at late stage
      originating in higher brain area in amblyopes hasn't been studied yet. The aim of
      this study was to investigate the late cognitive process at the frontal lobe in
      anisometropic amblyopes of a distinct degree, using visual event-related
      potential (ERP) techniques. METHODS: Thirteen severe anisometropic amblyopes, 14
      mild-to-moderate anisometropic amblyopes, and 13 control subjects participated in
      this study. Oddball paradigm (three stimuli: target, novel, and non-target
      stimuli) of low spatial frequency (1 cycle per degree, CPD) was used to elicit
      brain ERP waves. Reaction time, accuracy, latency, and amplitude of P3a waves
      evoked by novel stimuli at Fz electrode (the central electrode at frontal lobe),
      were analyzed statistically. RESULTS: Neither accuracy nor reaction time showed
      significant difference among the three groups. The latency of N200 wave showed no
      significant difference. The latency of P3a wave was delayed in the amblyopes
      compared with healthy controls, but there was no significant difference between
      severe and mild-to-moderate amblyopes. P3a amplitude in mild-to-moderate
      amblyopes was significantly higher than in controls and severe amblyopes.
      CONCLUSIONS: Our findings indicated that the cognitive process in anisometropic
      amblyopes was impaired, and the compensative effect of P3a amplitude was shown in
      mild-to-moderate amblyopes. P3a visual ERP could become a useful tool to
      investigate cognitive processing in amblyopes. Hippokratia 2016, 20(1): 60-66.

PMID- 27895446
TI  - A case of fatal sepsis due to multidrug-resistant Corynebacterium striatum.
AB  - BACKGROUND: Although non-diphtheria corynebacteria have traditionally been
      regarded as avirulent members of human bacterial flora, their pathogenic
      potential is increasingly recognized in our time. Reasons for this include the
      prolonged survival of severely ill and immunocompromised patients, the
      development of more invasive diagnostic and therapeutic procedures and the sub
      optimal use of antibiotics that disrupts normal microbial balance and favors
      superinfections. CASE REPORT: We present a rare case of sepsis due to multidrug
      resistant Corynebacterium striatum in a 76-year-old host. The patient suffered
      from myelodysplastic syndrome and was on corticosteroid treatment due to atopic
      dermatitis. He had, also, a recent hospital admission and received a course of
      broad-spectrum antibiotics due to lower respiratory infection. The patient
      responded neither to empiric nor to targeted treatment and finally succumbed.
      CONCLUSION: Diphtheroids are emerging pathogens capable of causing severe
      opportunistic infections. Their multidrugresistant nature renders treatment
      problematic and poses a threat to the currently established antimicrobial
      stewardship programs. Hippokratia 2016, 20(1): 67-69.

PMID- 27895447
TI  - Intrauterine device migration to the urinary bladder causing sexual dysfunction:
      a case report.
AB  - BACKGROUND: Intravesical migration represents an uncommon complication of
      intrauterine device (IUD) insertion. We present the case of an IUD that migrated
      to the urinary bladder, causing significant sexual complaints. CASE REPORT: A 38
      year-old woman presented with complaints of gradually evolving dyspareunia and
      recurrent urinary tract infections during the past 12 months. She reported an IUD
      insertion 18 months before. Further detailed evaluation revealed disorders in all
      sexual domains. Imaging and cystoscopy detected the presence of IUD in the
      urinary bladder. Under anesthesia, the IUD was removed out of the bladder without
      any complications. In her follow-up evaluation after six months, her sexual
      function was significantly improved and she had no urinary symptoms. CONCLUSION:
      Sexual difficulties in a woman with an IUD should raise the suspicion of device
      dislodgement or dislocation. Hippokratia 2016, 20(1): 70-72.

PMID- 27895448
TI  - Neonatal acute kidney injury following Valsartan exposure in utero: report of two
      cases.
AB  - BACKGROUND: Maternal sartan intake during pregnancy has been associated with
      several fetal/neonatal complications related to disturbed renal development.
      Description of cases: We present two cases of neonatal acute kidney injury (AKI)
      following valsartan administration during pregnancy and provide evidence for the
      use of novel AKI biomarkers in these neonates. The first case was a female
      neonate, delivered at 32+4 weeks of gestation after maternal valsartan intake
      from 24 to 32 gestational weeks. In the second case, ultrasound examination
      revealed a growth-restricted fetus with severe oligohydramnios following maternal
      valsartan intake during the first 29 gestational weeks. In the absence of any
      improvement in amniotic fluid, the neonate was born at 31+5 weeks. In both cases,
      AKI was documented after birth, but renal function progressively recovered. Urine
      cystatin-C and neutrophil gelatinase-associated lipocalin were found abnormally
      increased during the first week of life. CONCLUSION: Sartan use during pregnancy
      is associated with the development of neonatal AKI. Novel urine biomarkers may be
      used to document renal injury. Hippokratia 2016, 20(1): 73-75.

PMID- 27895449
TI  - CADASIL presenting with spontaneous intracerebral hemorrhage: report of a case
      and description of the first family in Northern Greece.
AB  - INTRODUCTION: CADASIL (cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy), the most common inherited cause of stroke and
      dementia in adults, has been described in six Greek families. Common presenting
      manifestations include migraine with aura, brain ischemia, mood disorders and
      cognitive decline. Spontaneous intracerebral hemorrhage (SICH) rarely occurs in
      CADASIL and only exceptionally as the first clinical manifestation. CASE
      DESCRIPTION: We have previously reported the sixth Greek family with CADASIL and
      in particular, two brothers in whom the genetic testing documented a classic
      mutation of the NOTCH3 gene (Arg169Cys). In this report, we describe the 30-year
      old son of the second brother, who suffered a thalamic SICH as the presenting
      manifestation of CADASIL, in the absence of arterial hypertension or antiplatelet
      drug use. CONCLUSION: Patients with acute subcortical infarcts,
      leukoencephalopathy, a history of migraine, mood disorders, and dementia, should
      always raise the suspicion of CADASIL. However, a SICH, even in the absence of
      classical risk factors for hemorrhage, is possible and should not exclude the
      diagnosis of CADACIL. Hippokratia 2016, 20(1): 76-79.

PMID- 27895450
TI  - Dermatofibrosarcoma protuberans: a case report and review of the literature.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) represents less than 0.1% of
      all tumors, but it is considered the most common skin sarcoma. Wide local
      excision (=5 cm) has been largely replaced by Mohs micrographic surgery; however,
      recurrence is not rare. Description of the case: A 35-year-old man presented with
      a large tumor on the upper side of his back and underwent local excision with the
      possible preoperative diagnosis of lipoma. Upon histological examination, the
      diagnosis of DFSP was made, and the patient underwent wide local excision with
      skin flap reconstruction and was referred for adjuvant radiotherapy.On twenty
      months follow-up, no recurrence has been observed. CONCLUSION: DFSP is the most
      common cutaneous sarcoma. It originates in the dermis and tends to infiltrate
      underlying structures, including muscles, tendons, fascia and bone. In our case,
      the tumor was confined to the skin and subcutaneous tissue, however, our patient
      underwent adjuvant radiotherapy to avoid a possible relapse that would infiltrate
      deeper structures. Long-term follow-up is strongly recommended. Hippokratia 2016,
      20(1): 80-83.

PMID- 27895451
TI  - Non-cardiogenic pulmonary edema, rhabdomyolysis and myocardial injury following
      heroin inhalation: a case report.
AB  - BACKGROUND: Heroin use by non-injecting routes of administration (snorting,
      swallowing, "chasing the dragon") is considered to be safer but is not risk-free
      for fatal overdose or serious side effects. We report the case of an adolescent
      who was transferred unconscious to the emergency department after heroin
      inhalation. Description of the case: A 17-year-old male was transferred to the
      emergency department unconscious (Glasgow coma scale: 6/15) after heroin
      inhalation. He was treated with non-rebreather mask and intravenous infusion of
      naloxone with gradual improvement of consciousness and arterial blood gasses. The
      chest computed tomography showed signs of acute respiratory distress syndrome.
      Laboratory exams on the second day of hospitalization showed elevated creatine
      kinase (CK) and troponin-I levels while his electrocardiography (ECG) showed J
      point elevation in V1, V2, and V3 precordial leads. On the second day of
      hospitalization the pulmonary infiltrates were not present in his chest X-ray
      while on the eighth day, troponin-I and CK levels were normalized without dynamic
      ECG changes and the patient was discharged uneventfully. CONCLUSION: Heroin
      inhalation may cause severe complications, such as non-cardiogenic pulmonary
      edema, rhabdomyolysis or myocardial injury. Hippokratia 2016, 20(1): 84-87.

PMID- 27895452
TI  - Laparoscopically assisted treatment of transverse testicular ectopia with
      persistent Mullerian duct syndrome: a case report and review of the literature.
AB  - BACKGROUND: Transverse testicular ectopia coexisting with persistent Mullerian
      duct syndrome is a rare malformation and evidence regarding the optimal treatment
      of these patients is still unclear. Description of the case: We present the case
      of a 4-month-old boy in whom laparoscopy was utilized for the surgical correction
      of transverse testicular ectopia and excision of Mullerian remnants. CONCLUSION:
      Based on current literature and the presented case, we support that laparoscopy
      is a feasible and safe procedure in patients with transverse testicular ectopia
      and persistent Mullerian duct syndrome. Hippokratia 2016, 20(1): 88-89.

PMID- 27895453
TI  - A case of a living-related kidney transplantation after ex-vivo repair of the
      donor renal artery aneurysm.
AB  - BACKGROUND: Kidney transplantation is the definite surgical treatment for end
      stage renal disease. Shortage of organs and the increasing number of patients
      with end-stage renal disease has led to an expansion of the selection criteria
      promoting the use of organs from marginal donors. Use of kidneys with renal
      artery aneurysm (RAA) is one such example. Description of the case: We report a
      case of living-related kidney transplantation from a 46-year-old female donor
      with unilateral RAA to her 68-year-old father. The pre-operative donor's
      assessment with a computed tomography angiogram revealed a saccular aneurysm of
      the left renal artery. The transplant team proceeded to the left nephrectomy,
      surgical ex vivo repair of the aneurysm and transplantation of this kidney to the
      recipient, with the total ischemic time of 130 minutes. At revascularization,
      there was no anastomotic leak with good perfusion of the organ and normal
      postoperative kidney function. CONCLUSION: RAA is a rare renal anatomical
      abnormality with unproven clinical significance. Advanced microvascular surgical
      techniques can be used to repair the aneurysm with subsequent successful use for
      transplantation. Hippokratia 2016, 20(1): 90-92.

PMID- 27895454
TI  - Diagnosis of type IV-A congenital choledochal cyst in a 73-year-old man.

PMID- 27895455
TI  - Soluble triggering receptor expressed on myelocytes-1 compared to procalcitonin
      in patients with infectious and autoimmune systemic inflammatory response
      syndrome.

PMID- 27895456
TI  - Acute necrotizing pancreatitis after chemoembolization for hepatocellular.

PMID- 27895457
TI  - Tracheo-innominate artery fistula: surgical primary closure of the artery defect,
      a successful treatment of a potential catastrophe.

PMID- 27895458
TI  - Clinical and imaging evaluation of the response to intravenous steroids in
      patients with Graves' orbitopathy and analysis on who requires additional
      therapy.
AB  - OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of an
      individualized steroid regimen in patients with moderate-to-severe Graves'
      orbitopathy (GO) by monitoring clinical and imaging parameters. METHODS: In
      total, 47 patients with active, moderate-to-severe GO were enrolled in this
      study. All the patients received the proposed treatment regimen by European Group
      on GO of 4.5 g of intravenous (IV) methylprednisolone for 12 weeks. At the end of
      the IV treatment, patients with persistent active GO (Group 1) who were assessed
      by clinical examination and orbital imaging with short tau inversion recovery
      sequence magnetic resonance imaging (STIR MRI) received additional treatment with
      oral prednisolone, and those with inactive GO (Group 2) received no further
      treatment. RESULTS: Of the 42 patients who completed the study, 22 (52.4%)
      patients formed Group 1 and 20 (47.6%) patients Group 2. At the 12th week, the
      overall response to IV treatment was 76.2%, and clinical activity score (CAS)
      improvement was 69%. At the 24th week, the overall response was 92.8%, and CAS
      improvement was 97.6%, without statistically significant difference in CAS and
      total eye score between these two groups (P=0.157 and P=0.856, respectively).
      Ophthalmic manifestations were improved, being absent or minimal in 78.6% of
      patients at the 24th week follow-up. Recurrence of disease activity occurred in
      9.5% of patients up to 24 weeks after the completion of treatment, and major
      adverse events occurred in 6.4% of patients. CONCLUSION: In patients with
      moderate-to-severe GO, IV steroid treatment, followed by oral treatment, when
      needed, is an effective regimen with low rates of adverse events and recurrences.
      STIR MRI is a significant tool for recognizing patients who need additional
      steroid treatment.

PMID- 27895460
TI  - Preoperative optical coherence tomography visualization of epiretinal membranes
      enhances surgical strategies.
AB  - PURPOSE: The aim of this study was to evaluate the usefulness of preoperative
      optical coherence tomography (OCT) findings in patients with macular epiretinal
      membrane (ERM) for the planning of surgical strategy. PATIENTS AND METHODS: One
      hundred twenty-three eyes of 121 patients (49 men, 72 women; mean age, 66 years)
      with an idiopathic ERM were enrolled. All patients underwent an ophthalmic
      examination including indirect ophthalmoscopy and OCT (Cirrus HD-OCT 4000 and/or
      5000). OCT images obtained using model 4000 were transferred to the model 5000
      system for vitreoretinal interface (VRI) analysis. The retinal thickness in each
      area, occurrence rate, and locations of the edges and partial detachments of the
      ERMs were evaluated using OCT. RESULTS: OCT detected identifiable edges in 61
      (50%) eyes and partial detachments in 116 (94%) of the 123 eyes. The edges and
      partial detachments were seen more frequently in the inferior macula. VRI
      analysis also detected the edges and partial detachments. Excluding the central
      area, the superior quadrant was the thickest in patients with an ERM. CONCLUSION:
      Preoperatively acquired OCT images are useful for planning surgical strategies
      and performing the surgeries smoothly.

PMID- 27895459
TI  - Amaurosis fugax - delay between symptoms and surgery by specialty.
AB  - PURPOSE: To describe the time course of management of patients with amaurosis
      fugax and analyze differences in management by different specialties. METHODS:
      Patients diagnosed with amaurosis fugax and subjected to carotid ultrasound in
      2004-2010 at the Sahlgrenska University Hospital, Gothenburg, Sweden (n=302) were
      included in this retrospective cohort study, and data were collected from medical
      records. RESULTS: The prevalence of significant carotid stenosis was 18.9%, and
      14.2% were subjected to carotid endarterectomy. A trend of longer delay for
      surgery was noted for patients first consulting a general practitioner (P=0.069)
      as compared to hospital-based specialties. For 46.3% of the patients, an
      ophthalmologist was their first medical contact. No significant difference in
      time interval to endarterectomy was seen between ophthalmologists and
      neurologists/internists. Only 31.8% of the patients with significant carotid
      stenosis had carotid endarterectomy within 2 weeks from the debut of symptoms,
      and this proportion was smaller for patients residing outside the Gothenburg city
      area (P=0.038). CONCLUSION: Initially consulting an ophthalmologist does not
      delay the time to ultrasound or carotid endarterectomy. The overall time from
      symptoms to surgery is longer than recommended for a majority of the patients,
      especially for patients from rural areas and for patients initially consulting a
      general practitioner.

PMID- 27895461
TI  - Sildenafil potentiates the antitumor activity of cisplatin by induction of
      apoptosis and inhibition of proliferation and angiogenesis.
AB  - Sildenafil is the first phosphodiesterase-5 inhibitor used for the treatment of
      erectile dysfunction. However, recent studies have been suggesting an antitumor
      effect of sildenafil. The current study assessed the aforementioned activity of
      sildenafil in vivo and in vitro in solid-tumor-bearing mice and in a human cell
      line MCF-7, respectively. Moreover, we investigated the impact of sildenafil on
      cisplatin antitumor activity. The solid tumor was induced by inoculation of
      Ehrlich ascites carcinoma cells in female mice. The tumor-bearing mice were
      assigned randomly to control (saline), sildenafil (sildenafil 5 mg/kg/d, PO daily
      for 15 days), cisplatin (cisplatin 7.5 mg/kg, IP once on the 12th day of Ehrlich
      ascites carcinoma inoculation), and combination therapy (cisplatin and
      sildenafil) groups. The tumor volume was measured at the end of the treatment
      period along with the following parameters: angiogenin, vascular endothelial
      growth factor, tumor necrosis factor-alpha, Ki-67, caspase-3, DNA-flow cytometry
      analysis, and histopathological examination. The study results showed that
      sildenafil has significantly decreased the tumor volume by 30.4%, angiogenin and
      tumor necrosis factor-alpha contents, as well as vascular endothelial growth
      factor expression. Additionally, caspase-3 level significantly increased with
      sildenafil treatment, whereas Ki-67 expression failed to show any significant
      changes. Furthermore, the cell cycle analysis revealed that sildenafil was
      capable of improving the category of tumor activity from moderate to low
      proliferative. Sildenafil induced necrosis in the tumor. Moreover, the drug of
      interest showed cytotoxic activity against MCF-7 in vitro as well as potentiated
      cisplatin antitumor activity in vivo and in vitro. These findings shed light on
      the antitumor activity of sildenafil and its possible impact on potentiating the
      antitumor effect of conventional chemotherapeutic agents such as cisplatin. These
      effects might be related to antiangiogenic, antiproliferative, and apoptotic
      activities of sildenafil.

PMID- 27895462
TI  - Effects of resveratrol on P-glycoprotein and cytochrome P450 3A in vitro and on
      pharmacokinetics of oral saquinavir in rats.
AB  - BACKGROUND: The intestinal cytochrome P450 3A (CYP 3A) and P-glycoprotein (P-gp)
      present a barrier to the oral absorption of saquinavir (SQV). Resveratrol (RESV)
      has been indicated to have modulatory effects on P-gp and CYP 3A. Therefore, this
      study was to investigate the effects of RESV on P-gp and CYP 3A activities in
      vitro and in vivo on oral SQV pharmacokinetics in rats. METHODS: In vitro,
      intestinal microsomes were used to evaluate RESV effect on CYP 3A-mediated
      metabolism of SQV; MDR1-expressing Madin-Darby canine kidney (MDCKII-MDR1) cells
      were employed to assess the impact of RESV on P-gp-mediated efflux of SQV. In
      vivo effects were studied using 10 rats randomly assigned to receive oral SQV (30
      mg/kg) with or without RESV (20 mg/kg). Serial blood samples were obtained over
      the following 24 h. Concentrations of SQV in samples were ascertained using high
      performance liquid chromatography-tandem mass spectrometry analysis. RESULTS:
      RESV (1-100 MUM) enhanced residual SQV (% of control) in a dose-dependent manner
      after incubation with intestinal microsomes. RESV (1-100 MUM) reduced the
      accumulation of SQV in MDCKII-MDR1 cells in a concentration-dependent manner. A
      double peaking phenomenon was observed in the plasma SQV profiles in rats. The
      first peak of plasma SQV concentration was increased, but the second peak was
      reduced by coadministration with RESV. The mean AUC0-infinity of SQV was slightly
      decreased, with no statistical significance probably due to the high individual
      variation. CONCLUSION: RESV can alter the plasma SQV concentration profiles,
      shorten the Tmax of SQV. RESV might also cause a slight decrease tendency in the
      SQV bioavailability in rats.

PMID- 27895463
TI  - Lentivirus-mediated knockdown of NLK inhibits small-cell lung cancer growth and
      metastasis.
AB  - Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, has
      been recognized as a critical regulator of various cancers. In this study, we
      investigated the role of NLK in human small-cell lung cancer (SCLC), which is the
      most aggressive form of lung cancer. NLK expression was evaluated by quantitative
      real-time polymerase chain reaction in 20 paired fresh SCLC tissue samples and
      found to be noticeably elevated in tumor tissues. Lentivirus-mediated RNAi
      efficiently suppressed NLK expression in NCI-H446 cells, resulting in a
      significant reduction in cell viability and proliferation in vitro. Moreover,
      knockdown of NLK led to cell cycle arrest at the S-phase via suppression of
      Cyclin A, CDK2, and CDC25A, which could contribute to cell growth inhibition.
      Furthermore, knockdown of NLK decreased the migration of NCI-H446 cells and
      downregulated matrix metalloproteinase 9. Treatment with NLK short hairpin RNA
      significantly reduced SCLC tumor growth in vivo. In conclusion, this study
      suggests that NLK plays an important role in the growth and metastasis of SCLC
      and may serve as a potential therapeutic target for the treatment of SCLC.

PMID- 27895464
TI  - Selexipag in the treatment of pulmonary arterial hypertension: design,
      development, and therapy.
AB  - Pulmonary arterial hypertension is characterized by abnormalities in the small
      pulmonary arteries including increased vasoconstriction, vascular remodeling,
      proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel,
      oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a
      phase II clinical trial and reduce clinical worsening in a large phase III
      clinical trial involving patients with pulmonary arterial hypertension. In this
      paper, we describe the prostacyclin signaling pathway, currently available oral
      prostanoid medications, and the development and clinical use of selexipag.

PMID- 27895465
TI  - Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of
      dacarbazine for malignant melanoma.
AB  - Conditionally replicating adenoviruses have emerged as novel therapeutic agents
      for cancer. This study aimed to evaluate synergistic antitumor activity of
      replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and
      dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor
      xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results
      showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18,
      and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC
      accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically
      inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited
      vascular endothelial growth factor expression and lung metastasis in xenografts
      of nude mice. In conclusion, this is the first study to show synergistic
      anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results
      provide evidence that chemo-gene-viro therapeutic approach has greater potential
      for malignant cancers than conventional chemotherapy or gene therapy.

PMID- 27895466
TI  - Pharmacokinetics, pharmacodynamics and safety of CKD-519, a CETP inhibitor, in
      healthy subjects.
AB  - CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP)
      inhibitor being developed for the treatment of dyslipidemia to raise high-density
      lipoprotein cholesterol. We investigated the safety, tolerability,
      pharmacokinetics, and pharmacodynamics of single doses of CKD-519 in healthy
      adult subjects. A randomized, double-blinded, placebo-controlled, single
      ascending dose study was performed. Eight healthy subjects were enrolled in each
      CKD-519 dose group (25, 50, 100, 200, or 400 mg) and randomized to CKD-519 (n=6)
      or matching placebo (n=2). CKD-519 reached the maximum plasma concentration
      (Cmax) at 5-6 h post-dose, and had a long terminal half-life ranging between 40
      70 h. The area under the plasma concentration-time curve (AUC) and Cmax increased
      with the dose, however, Cmax and AUC normalized by dose decreased with each
      incremental dose. CETP activity decreased with dose, and the maximum decrease
      (63%-83%) was observed at 6-8 h post-dose. A sigmoid Emax model best described
      the relationship between CKD-519 plasma concentrations and CETP activity with an
      EC50 of 17.3 ng/mL. Overall, 11 adverse events (AEs) were observed. All AEs were
      mild or moderate in intensity, and resolved without any complications. There were
      no clinically significant effects on blood pressure. In conclusion, single doses
      of CKD-519 up to 400 mg were well tolerated and showed potent inhibition of CETP
      activity.

PMID- 27895468
TI  - Increased localized delivery of piroxicam by cationic nanoparticles after intra
      articular injection.
AB  - Piroxicam (PRX), a potent nonsteroidal anti-inflammatory drug, is prescribed to
      relieve postoperative and/or chronic joint pain. However, its oral administration
      often results in serious gastrointestinal adverse effects including duodenal
      ulceration. Thus, a novel cationic nanoparticle (NP) was explored to minimize the
      systemic exposure and increase the retention time of PRX in the joint after intra
      articular (IA) injection, by forming micrometer-sized electrostatic clusters with
      endogenous hyaluronic acid (HA) in the synovial cavity. PRX-loaded NPs consisting
      of poly(lactic-co-glycolic acid), Eudragit RL, and polyvinyl alcohol were
      constructed with the following characteristics: particle size of 220 nm, zeta
      potential of 11.5 mV in phosphate-buffered saline, and loading amount of 4.0%
      (w/w) of PRX. In optical and hyperspectral observations, the cationic NPs formed
      more than 50 MUm-sized aggregates with HA, which was larger than the
      intercellular gaps between synoviocytes. In an in vivo pharmacokinetic study in
      rats, area under the plasma concentration-time curve (AUC0-24 h) and maximum
      plasma concentration (Cmax) of PRX after IA injection of the cationic NPs were
      <70% (P<0.05) and 60% (P<0.05), respectively, compared to those obtained from
      drug solution. Moreover, the drug concentration in joint tissue 24 h after dosing
      with the cationic NPs was 3.2-fold (P<0.05) and 1.8-fold (P<0.05) higher than
      that from drug solution and neutrally charged NPs, respectively. Therefore, we
      recommend the IA cationic NP therapy as an effective alternative to traditional
      oral therapy with PRX, as it increases drug retention selectively in the joint.

PMID- 27895470
TI  - Validity of the Control Preferences Scale in patients with emotional disorders.
AB  - BACKGROUND: The Control Preferences Scale (CPS) is the most frequently used
      measure of patients' preferred roles in treatment decisions. The aim of this
      study was to provide data about the validity of CPS in psychiatric care of
      patients with emotional disorders. METHODS: The original CPS was translated to
      Spanish using the process of cross-cultural adaptation of self-reported measures
      as the methodological model for Spanish translation. The final version was tested
      in a convenience sample of 621 consecutive psychiatric outpatients (461
      depressive and 160 anxiety disorders) that also completed the Shared Decision
      Making Questionnaire, the Multidimensional Health Locus of Control Scale, the
      Drug Attitude Inventory, and a questionnaire including sociodemographic and
      clinical variables. RESULTS: CPS showed a moderate internal consistency and a
      good convergent validity. Patients with collaborative and passive preferences
      expressed a greater reliance on psychotropics. Patients preferring a
      collaborative role self-reported greater perception of involvement in decision
      making about their treatment. Patients preferring a passive role showed a greater
      external health locus of control. The most common preferred role was the
      collaborative-passive. Older patients and those under longer treatments preferred
      a passive role, while patients with higher levels of education preferred a
      collaborative role. CONCLUSION: The CPS is a valid measure of the amount of
      control that psychiatric outpatients with emotional disorders want to assume in
      the process of making decisions about their treatment.

PMID- 27895467
TI  - Dietary arginine silicate inositol complex inhibits periodontal tissue loss in
      rats with ligature-induced periodontitis.
AB  - The purpose of this study was to induce experimental periodontitis in rats
      previously fed diets containing arginine silicate inositol (ASI) complex and
      examine the biochemical, immunological, and radiological effects. Fifty two 8
      week-old female Sprague Dawley rats were equally divided into four groups. The
      control group included those fed a standard rat diet with no operation performed
      during the experiment. The periodontitis, ASI I, and ASI II groups were subjected
      to experimental periodontitis induction for 11 days after being fed a standard
      rat diet alone, a diet containing 1.81 g/kg ASI complex, or a diet containing
      3.62 g/kg ASI complex, respectively, for 8 weeks. Throughout the 11-day duration
      of periodontitis induction, all rats were fed standard feed. The rats were
      euthanized on the eleventh day, and their tissue and blood samples were
      collected. In the periodontitis group, elevated tissue destruction parameters and
      reduced tissue formation parameters were found, as compared to the ASI groups.
      Levels of enzymes, cytokines, and mediators associated with periodontal tissue
      destruction were lower in rats fed a diet containing ASI complex after
      experimental periodontitis. These results indicate that ASI complex could be an
      alternative agent for host modulation.

PMID- 27895469
TI  - Comparison of bile salt/phosphatidylcholine mixed micelles in solubilization to
      sterols and stability.
AB  - Androst-3beta,5alpha,6beta-triol (Triol) is a promising neuroprotective agent,
      but its poor solubility restricts its development into parenteral preparations.
      In this study, Triol is significantly solubilized by bile
      salt/phosphatidylcholine mixed micelles (BS/PC-MM). All BS/PC-MM systems are
      tested to remarkably improve the drug solubility with various stabilities after
      drug loading. Among them, the sodium glycocholate (SGC)/egg phosphatidylcholine
      (EPC) system with 2:1 ratio in weight and the total concentration of SGC and EPC
      of 100 mg/mL is proved to produce stable mixed micelles with high drug loading.
      It is found that the stability of drug-loaded mixed micelles is quite different,
      which might be related to the change in critical micelle concentration (CMC)
      after incorporating drugs. SGC/EPC and SGC/soya phosphatidylcholine (SPC) remain
      transparent under accelerated conditions and manifest a decreased CMC (dropping
      from 0.105 to 0.056 mg/mL and from 0.067 to 0.024 mg/mL, respectively). In
      contrast, swine bile acid-sodium salt (SBA-Na)/PC and sodium deoxycholate
      (SDC)/PC are accompanied by drug precipitation and reached the maximum CMC on the
      first and the third days, respectively. Interestingly, the variation of CMC under
      accelerated testing conditions highly matches the drug-precipitating event in the
      primary stability experiment. In brief, the bile salt/phosphatidylcholine system
      exists as a potential strategy of improving sterol drug solubility. CMC variation
      under accelerated testing conditions might be a simple and easy method to predict
      the stability of drug-loaded mixed micelles.

PMID- 27895471
TI  - Adherence, satisfaction and preferences for treatment in patients with psoriasis
      in the European Union: a systematic review of the literature.
AB  - BACKGROUND AND OBJECTIVE: Adherence to treatment in patients with psoriasis is
      often poor. An investigation of patient preferences and satisfaction with
      treatment may be important, based on the expected correlation with therapy
      compliance. This paper aims to examine and describe the current literature on
      patient preferences, satisfaction and adherence to treatment for psoriasis in the
      European Union (EU). METHODS: Electronic searches were conducted using PubMed,
      ISI Web of Knowledge, Scopus, Spanish databases and Google Scholar. European
      studies published in English or Spanish between January 1, 2009 and December 31,
      2014 regarding patient-reported outcomes in psoriatic patients were included.
      Studies conducted in non-EU countries, letters to the editor, editorials,
      experts' opinions, case studies, congress proceedings, publications that did not
      differentiate between patients with psoriasis and psoriatic arthritis or studies
      related to specific treatment were excluded. RESULTS: A total of 1,769 titles
      were identified, of which 1,636 were excluded as they were duplicates or did not
      provide any relevant information. After a full-text reading and application of
      the inclusion/exclusion criteria, 46 publications were included. This paper will
      describe publications on adherence (n=4), preferences (n=5) and satisfaction with
      treatment (n=7). Results related to health-related quality of life articles
      (n=30) have been published elsewhere. Adherence rates are generally low in
      psoriasis patients regardless of the type of treatment, severity of disease or
      methods used to measure adherence. Biologic therapy is associated with greater
      clinical improvement. There is a direct association between physician
      recommendations, patient preferences and several domains of treatment
      satisfaction. CONCLUSION: The results of this review support the conclusion that
      adherence rates in patients with psoriasis are suboptimal and highlight the need
      to improve patient compliance and satisfaction with treatment. Patients'
      preferences should be taken into account in the treatment decision-making process
      in order to improve patients' clinical outcomes by ensuring satisfaction and
      adherence.

PMID- 27895473
TI  - Calf-raise senior: a new test for assessment of plantar flexor muscle strength in
      older adults: protocol, validity, and reliability.
AB  - PURPOSE: This study aimed to develop a new field test protocol with a
      standardized measurement of strength and power in plantar flexor muscles targeted
      to functionally independent older adults, the calf-raise senior (CRS) test, and
      also evaluate its reliability and validity. PATIENTS AND METHODS: Forty-one
      subjects aged 65 years and older of both sexes participated in five different
      cross-sectional studies: 1) pilot (n=12); 2) inter- and intrarater agreement
      (n=12); 3) construct (n=41); 4) criterion validity (n=33); and 5) test-retest
      reliability (n=41). Different motion parameters were compared in order to define
      a specifically designed protocol for seniors. Two raters evaluated each
      participant twice, and the results of the same individual were compared between
      raters and participants to assess the interrater and intrarater agreement. The
      validity and reliability studies involved three testing sessions that lasted 2
      weeks, including a battery of functional fitness tests, CRS test in two
      occasions, accelerometry, and strength assessments in an isokinetic dynamometer.
      RESULTS: The CRS test presented an excellent test-retest reliability (intraclass
      correlation coefficient [ICC] =0.90, standard error of measurement =2.0) and
      interrater reliability (ICC =0.93-0.96), as well as a good intrarater agreement
      (ICC =0.79-0.84). Participants with better results in the CRS test were younger
      and presented higher levels of physical activity and functional fitness. A
      significant association between test results and all strength parameters
      (isometric, r=0.87, r2=0.75; isokinetic, r=0.86, r2=0.74; and rate of force
      development, r=0.77, r2=0.59) was shown. CONCLUSION: This study was successful in
      demonstrating that the CRS test can meet the scientific criteria of validity and
      reliability. The test can be a good indicator of ankle strength in older adults
      and proved to discriminate significantly between individuals with improved
      functionality and levels of physical activity.

PMID- 27895472
TI  - Safety and effectiveness of daily teriparatide for osteoporosis in patients with
      severe stages of chronic kidney disease: post hoc analysis of a postmarketing
      observational study.
AB  - Teriparatide (recombinant 1-34 N-terminal sequence of human parathyroid hormone)
      for the treatment of osteoporosis should be prescribed with caution in patients
      with severe stages of chronic kidney disease (CKD). However, in clinical
      settings, physicians and surgeons who treat such patients have few available
      options. We sought to further explore the safety and effectiveness of
      teriparatide for the treatment of osteoporosis in Japanese patients with severe
      stages of CKD. This was a post hoc analysis of a postmarketing surveillance study
      that included patients with osteoporosis at high risk of fracture and stage 4 or
      5 CKD. Patients received subcutaneous teriparatide 20 MUg daily for up to 24
      months. Safety profiles were assessed by physician-reported adverse drug
      reactions (ADRs). Effectiveness was assessed by measuring bone formation (via
      procollagen type 1 N-terminal propeptide [P1NP]), bone mineral density (BMD), and
      the incidence of clinical vertebral or nonvertebral fragility fractures. A total
      of 33 patients with severe stages of CKD (stage 4, n=30; stage 5, n=3) were
      included. All patients were female, and 81.8% had a history of previous fracture.
      No serious ADRs were recorded; a total of 4 ADRs were recorded for 4 of 33
      patients. Increases in BMD and P1NP levels were observed both overall and in most
      individual patients. New fractures occurred in 1 patient with stage 5 CKD, but
      not in patients with stage 4 CKD. In this post hoc analysis conducted in Japan,
      teriparatide appeared to be effective for the treatment of osteoporosis in
      elderly female patients with severe stages of CKD, and no new safety concerns
      were observed.

PMID- 27895474
TI  - Efficacy of L-carnitine supplementation on frailty status and its biomarkers,
      nutritional status, and physical and cognitive function among prefrail older
      adults: a double-blind, randomized, placebo-controlled clinical trial.
AB  - BACKGROUND: Frailty is a biological syndrome of decreased reserve and resistance
      to stressors due to decline in multiple physiological systems. Amino acid
      deficiency, including L-carnitine, has been proposed to be associated with its
      pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on
      frailty status has not been documented. Thus, this study aimed to determine the
      effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its
      biomarkers and also physical function, cognition, and nutritional status among
      prefrail older adults in Klang Valley, Malaysia. METHODOLOGY: This study is a
      randomized, double-blind, placebo-controlled clinical trial conducted among 50
      prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in
      placebo group). Outcome measures include frailty status using Fried criteria and
      Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin
      6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical
      function, cognitive function, nutritional status and biochemical profile.
      RESULTS: The results indicated that the mean scores of Frailty Index score and
      hand grip test were significantly improved in subjects supplemented with L
      carnitine (P<0.05 for both parameters) as compared to no change in the placebo
      group. Based on Fried criteria, four subjects (three from the L-carnitine group
      and one from the control group) transited from prefrail status to robust after
      the intervention. CONCLUSION: L-carnitine supplementation has a favorable effect
      on the functional status and fatigue in prefrail older adults.

PMID- 27895475
TI  - Transcranial direct current stimulation improves the QT variability index and
      autonomic cardiac control in healthy subjects older than 60 years.
AB  - BACKGROUND: Noninvasive brain stimulation technique is an interesting tool to
      investigate the causal relation between cortical functioning and autonomic
      nervous system (ANS) responses. OBJECTIVE: The objective of this report is to
      evaluate whether anodal transcranial direct current stimulation (tDCS) over the
      temporal cortex influences short-period temporal ventricular repolarization
      dispersion and cardiovascular ANS control in elderly subjects. SUBJECTS AND
      METHODS: In 50 healthy subjects (29 subjects younger than 60 years and 21
      subjects older than 60 years) matched for gender, short-period RR and systolic
      blood pressure spectral variability, QT variability index (QTVI), and noninvasive
      hemodynamic data were obtained during anodal tDCS or sham stimulation. RESULTS:
      In the older group, the QTVI, low-frequency (LF) power expressed in normalized
      units, the ratio between LF and high-frequency (HF) power, and systemic
      peripheral resistances decreased, whereas HF power expressed in normalized units
      and alpha HF power increased during the active compared to the sham condition
      (P<0.05). CONCLUSION: In healthy subjects older than 60 years, tDCS elicits
      cardiovascular and autonomic changes. Particularly, it improves temporal
      ventricular repolarization dispersion, reduces sinus sympathetic activity and
      systemic peripheral resistance, and increases vagal sinus activity and baroreflex
      sensitivity.

PMID- 27895477
TI  - Noninvasive monitoring of early antiangiogenic therapy response in human
      nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall
      superparamagnetic iron oxide nanoparticles.
AB  - PURPOSE: Arginine-glycine-aspartic acid (RGD)-based nanoprobes allow specific
      imaging of integrin alphavbeta3, a protein overexpressed during angiogenesis.
      Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA)-coated
      ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-PAA-USPIO) in
      order to detect tumor angiogenesis and assess the early response to
      antiangiogenic treatment in human nasopharyngeal carcinoma (NPC) xenograft model
      by magnetic resonance imaging (MRI). MATERIALS AND METHODS: The binding
      specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs)
      was confirmed by Prussian blue staining and transmission electron microscopy in
      vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft
      model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days
      of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per
      group). RESULTS: The specific uptake of the RGD-PAA-USPIO nanoparticles was
      mainly dependent on the interaction between RGD and integrin alphavbeta3 of
      HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft
      model. Moreover, the T2 relaxation time of mice in the Endostar-treated group
      decreased significantly compared with those in the control group both on days 4
      and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05).
      CONCLUSION: This study demonstrated that the magnetic resonance molecular
      nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor
      angiogenesis and assessment of the early response to antiangiogenic treatment in
      NPC xenograft model, favoring its potential clinical translation.

PMID- 27895476
TI  - Community-based exercise training for people with chronic respiratory and chronic
      cardiac disease: a mixed-methods evaluation.
AB  - BACKGROUND: Poor uptake and adherence are problematic for hospital-based
      pulmonary and heart failure rehabilitation programs, often because of access
      difficulties. The aims of this mixed-methods study were to determine the
      feasibility of a supervised exercise training program in a community gymnasium in
      people with chronic respiratory and chronic cardiac disease, to explore the
      experiences of participants and physiotherapists and to determine if a community
      venue improved access and adherence to rehabilitation. METHODS: Adults with
      chronic respiratory and/or chronic cardiac disease referred to a hospital-based
      pulmonary and heart failure rehabilitation program were screened to determine
      their suitability to exercise in a community venue. Eligible patients were
      offered the opportunity to attend supervised exercise training for 8 weeks in a
      community gymnasium. Semi-structured interviews were conducted with participants
      and physiotherapists at the completion of the program. RESULTS: Thirty-one people
      with chronic respiratory and chronic cardiac disease (34% males, mean [standard
      deviation] age 72 [10] years) commenced the community-based exercise training
      program. Twenty-two (71%) completed the program. All participants who completed
      the program, and the physiotherapists delivering the program, were highly
      satisfied, with reports of the community venue being well-equipped, convenient,
      and easily accessible. Using a community gymnasium promoted a sense of normality
      and instilled confidence in some to continue exercising at a similar venue post
      rehabilitation. However, factors such as cost and lack of motivation continue to
      be barriers. CONCLUSION: The convenience and accessibility of a community venue
      for rehabilitation contributed to high levels of satisfaction and a positive
      experience for people with chronic respiratory and chronic cardiac disease and
      physiotherapists.

PMID- 27895478
TI  - Biosynthesis, characterization, and evaluation of bioactivities of leaf extract
      mediated biocompatible silver nanoparticles from an early tracheophyte, Pteris
      tripartita Sw.
AB  - The objective of the study was to characterize silver nanoparticles (Ag-NPs) and
      their bioactivities in early tracheophytes (Pteridophyta). Aqueous leaf extract
      of a critically endangered fern, Pteris tripartita Sw., was used for one-step
      green synthesis of Ag-NPs. The biosynthesized Ag-NPs were characterized using
      ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy,
      scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray
      diffraction, and high-resolution transmission electron microscopy.
      Morphologically, the Ag-NPs showed hexagonal, spherical, and rod-shaped
      structures. Size distributions of Ag-NPs, calculated using Scherrer's formula,
      showed an average size of 32 nm. Ag-NPs were studied for in vitro antioxidant,
      antimicrobial, and in vivo anti-inflammatory activities. Ag-NPs exhibited
      significant anti-inflammatory activity in carrageenan-induced paw volume tests
      performed in female Wistar albino rats. Furthermore, Ag-NPs showed significant
      antimicrobial activity against 12 different microorganisms in three different
      assays (disk diffusion, time course growth, and minimum inhibitory
      concentration). This study reports that colloidal Ag-NPs can be synthesized by
      simple, nonhazardous methods, and that biosynthesized Ag-NPs have significant
      therapeutic properties.

PMID- 27895479
TI  - Cationic PEGylated liposomes incorporating an antimicrobial peptide tilapia
      hepcidin 2-3: an adjuvant of epirubicin to overcome multidrug resistance in
      cervical cancer cells.
AB  - Antimicrobial peptides (AMPs) have been recently evaluated as a new generation of
      adjuvants in cancer chemotherapy. In this study, we designed PEGylated liposomes
      encapsulating epirubicin as an antineoplastic agent and tilapia hepcidin 2-3, an
      AMP, as a multidrug resistance (MDR) transporter suppressor and an
      apoptosis/autophagy modulator in human cervical cancer HeLa cells. Cotreatment of
      HeLa cells with PEGylated liposomal formulation of epirubicin and hepcidin 2-3
      significantly increased the cytotoxicity of epirubicin. The liposomal
      formulations of epirubicin and/or hepcidin 2-3 were found to noticeably escalate
      the intracellular H2O2 and O2- levels of cancer cells. Furthermore, these
      treatments considerably reduced the mRNA expressions of MDR protein 1, MDR
      associated protein (MRP) 1, and MRP2. The addition of hepcidin 2-3 in liposomes
      was shown to markedly enhance the intracellular epirubicin uptake and mainly
      localized into the nucleus. Moreover, this formulation was also found to trigger
      apoptosis and autophagy in HeLa cells, as validated by significant increases in
      the expressions of cleaved poly ADP ribose polymerase, caspase-3, caspase-9, and
      light chain 3 (LC3)-II, as well as a decrease in mitochondrial membrane
      potential. The apoptosis induction was also confirmed by the rise in sub-G1 phase
      of cell cycle assay and apoptosis percentage of annexin V/propidium iodide assay.
      We found that liposomal epirubicin and hepcidin 2-3 augmented the accumulation of
      GFP-LC3 puncta as amplified by chloroquine, implying the involvement of
      autophagy. Interestingly, the partial inhibition of necroptosis and the
      epithelial-mesenchymal transition by this combination was also verified.
      Altogether, our results provide evidence that coincubation with PEGylated
      liposomes of hepcidin 2-3 and epirubicin caused programmed cell death in cervical
      cancer cells through modulation of multiple signaling pathways, including MDR
      transporters, apoptosis, autophagy, and/or necroptosis. Thus, this formulation
      may provide a new platform for the combined treatment of traditional chemotherapy
      and hepcidin 2-3 as a new adjuvant for effective MDR reversal.

PMID- 27895481
TI  - Polyethyleneimine-coated quantum dots for miRNA delivery and its enhanced
      suppression in HepG2 cells.
AB  - Quantum dots (QDs) have been intensively investigated for bioimaging, drug
      delivery, and labeling probes because of their unique optical properties. In this
      study, CdSe/ZnS QDs-based nonviral vectors with the dual functions of delivering
      miR-26a plasmid and bioimaging were formulated by capping the surface of CdSe/ZnS
      QDs with polyethyleneimine (PEI). The PEI-coated QDs were capable of condensing
      miR-26a expression vector into nanocomplexes that can emit strong red
      luminescence when loaded with CdSe/ZnS QDs. Further results showed that PEI
      modified nanoparticles (NPs) could transfect miR-26a plasmid into HepG2 cells in
      vitro. Meanwhile, imaging of living cells could be achieved based on the CdSe/ZnS
      QDs. Further study suggested that miR-26a transfection up-regulated miR-26a
      expression, induced cycle arrest, and triggered proliferation inhibition in HepG2
      cells. The results indicated that PEI-coated QD NPs possess the capability of
      bioimaging and gene delivery and could be a promising vehicle with the
      engineering of QD NPs for gene therapy in the future.

PMID- 27895480
TI  - Synthesis of three-arm block copolymer poly(lactic-co-glycolic acid)
      poly(ethylene glycol) with oxalyl chloride and its application in hydrophobic
      drug delivery.
AB  - PURPOSE: Synthesis of star-shaped block copolymer with oxalyl chloride and
      preparation of micelles to assess the prospect for drug-carrier applications.
      MATERIALS AND METHODS: Three-arm star block copolymers of poly(lactic-co-glycolic
      acid) (3S-PLGA)-polyethylene glycol (PEG) were synthesized by ring-opening
      polymerization, then PEG as the hydrophilic block was linked to the terminal
      hydroxyl of 3S-PLGA with oxalyl chloride. Fourier-transform infrared (FT-IR)
      spectroscopy, gel-permeation chromatography (GPC), hydrogen nuclear magnetic
      resonance (1H-NMR) spectra, and differential scanning calorimetry were employed
      to identify the structure and properties of 3S-PLGA-PEG. Rapamycin (RPM)-loaded
      micelles were prepared by solvent evaporation, and pyrene was used as the
      fluorescence probe to detect the critical micelle concentration of the copolymer.
      The particle size, distribution, and zeta-potential of the micelles were
      determined by dynamic light scattering, and the morphology of the RPM-loaded
      micelles was analyzed by transmission electron microscopy. High-performance
      liquid chromatography was conducted to analyze encapsulation efficiency and drug
      loading capacity, as well as the release behavior of RPM-loaded micelles. The
      biocompatibility of material and the cytostatic effect of RPM-loaded micelles
      were investigated by Cell Counting Kit 8 assay. RESULTS: FT-IR, GPC, and 1H-NMR
      suggested that 3S-PLGA-PEG was successfully synthesized. The RPM-loaded micelles
      prepared with the 3S-PLGA-PEG possessed good properties. The micelles had good
      average diameter and encapsulation efficiency. For in vitro release, RPM was
      released slowly from 3S-PLGA-PEG micelles, showing that 3S-PLGA-PEG-RPM exhibited
      a better and longer antiproliferative effect than free RPM. CONCLUSION: In this
      study, we first used oxalyl chloride as the linker to synthesize 3S-PLGA-PEG
      successfully, and compared with reported literature, this method shortened the
      reaction procedure and improved the reaction yield. The micelles prepared with
      this material proved suitable for drug-carrier application.

PMID- 27895482
TI  - Nanoparticle-based strategy for personalized B-cell lymphoma therapy.
AB  - B-cell lymphoma is associated with incomplete response to treatment, and the
      development of effective strategies targeting this disease remains challenging. A
      new personalized B-cell lymphoma therapy, based on a site-specific receptor
      mediated drug delivery system, was developed in this study. Specifically, natural
      silica-based nanoparticles (diatomite) were modified to actively target the
      antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA
      (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the
      hypervariable region of surface immunoglobulin B-cell receptor was exploited as a
      homing device to ensure specific targeting of lymphoma cells. Specific
      nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry
      and confocal microscopy and was increased by approximately threefold in target
      cells compared with nonspecific myeloma cells and when a random control peptide
      was used instead of Id-peptide. The specific internalization efficiency was
      increased by fourfold when siRNA was also added to the modified nanoparticles.
      The modified diatomite particles were not cytotoxic and their effectiveness in
      downregulation of gene expression was explored using siRNA targeting Bcl2 and
      evaluated by quantitative real-time polymerase chain reaction and Western blot
      analyses. The resulting gene silencing observed is of significant biological
      importance and opens new possibilities for the personalized treatment of
      lymphomas.

PMID- 27895483
TI  - Improved proliferation of antigen-specific cytolytic T lymphocytes using a
      multimodal nanovaccine.
AB  - The present study investigated the immunoenhancing property of our newly designed
      nanovaccine, that is, its ability to induce antigen-specific immunity. This study
      also evaluated the synergistic effect of a novel compound PBS-44, an alpha
      galactosylceramide analog, in boosting the immune response induced by our
      nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova) and an
      adjuvant within the poly(lactic-co-glycolic acid) nanoparticles. Quantitative
      analysis of our study data showed that the encapsulated vaccine was physically
      and biologically stable; the core content of our nanovaccine was found to be
      released steadily and slowly, and nearly 90% of the core content was slowly
      released over the course of 25 days. The in vivo immunization studies exhibited
      that the nanovaccine induced stronger and longer immune responses compared to its
      soluble counterpart. Similarly, intranasal inhalation of the nanovaccine induced
      more robust antigen-specific CD8+ T cell response than intraperitoneal injection
      of nanovaccine.

PMID- 27895484
TI  - The effect of dexamethasone/cell-penetrating peptide nanoparticles on gene
      delivery for inner ear therapy.
AB  - Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were
      developed for the delivery of genes to determine the synergistic effect of Dex on
      gene expression. The cationic PCA nanoparticles were self-assembled to create
      cationic micelles containing an octadecylamine (C18) core with Dex and an
      arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids
      (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived
      neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8,
      a cell-penetrating peptide that enhances permeability through a round window
      membrane in the inner ear for gene delivery, exhibited high uptake efficiency in
      HEI-OC1 cells. This potential carrier co-delivering Dex and the gene into inner
      ear cells has a diameter of 120-140 nm and a zeta potential of 20-25 mV.
      Different types of genes were complexed with the Dex-loaded PCA nanoparticle
      (PCA/Dex/gene) for gene expression to induce additional anti-inflammatory
      effects. PCA/Dex showed mildly increased expression of GFP and lower mRNA
      expression of inflammatory cytokines (IL1b, IL12, and INFr) than did Dex-free PCA
      nanoparticles and Lipofectamine(r) reagent in HEI-OC1 cells. In addition, after
      loading Cx26 siRNA onto the surface of PCA/Dex, Cx26 gene expression was
      downregulated according to real-time polymerase chain reaction for 24 h, compared
      with that using Lipofectamine reagent. After loading BDNF DNA into PCA/Dex,
      increased expression of BDNF was observed for 30 h, and its signaling pathway
      resulted in an increase in phosphorylation of Akt, observed by Western blotting.
      Thus, Dex within PCA/Dex/gene nanoparticles created an anti-inflammatory effect
      and enhanced gene expression.

PMID- 27895485
TI  - ADHD and Present Hedonism: time perspective as a potential diagnostic and
      therapeutic tool.
AB  - The article draws primarily from the behavioral findings (mainly psychiatric and
      psychological observations) and points out the important relationships between
      attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation.
      Specifically, the authors argue that there is a significant overlap between the
      symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo's
      time perspective theory and assessed by Zimbardo Time Perspective Inventory.
      Developmental data on Present Hedonism of males and females in the Czech
      population sample (N=2201) are also presented. The hypothesis of relationship
      between ADHD and Present Hedonism is mainly derived from the prevalence of
      addictive behavior (mainly excessive Internet use, alcohol abuse, craving for
      sweets, fatty foods, and fast foods), deficits in social learning, and increased
      aggressiveness both in ADHD and in the population scoring high on Present
      Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo's
      time perspective offers both: 1) a potential diagnostic tool - the Zimbardo Time
      Perspective Inventory, particularly its Present Hedonism scale, and 2) a
      promising preventive and/or therapeutic approach by the Time Perspective Therapy.
      Time Perspective Therapy has so far been used mainly to treat past negative
      trauma (most notably, posttraumatic stress disorder); however, it also has value
      as a potential therapeutic tool for possible behavioral compensation of ADHD.

PMID- 27895486
TI  - Factors associated with vitamin D status of low-income, hospitalized psychiatric
      patients: results of a retrospective study.
AB  - BACKGROUND: Recent evidence has indicated a potential role of vitamin D3 in a
      range of neuropsychiatric outcomes, as well as on cognitive function, but
      conflicting data have left that role uncertain. Understanding potential
      associations of vitamin D status with psychiatric illness will allow clinicians
      to better assess therapeutic options. Few studies have examined vitamin D status
      among a racially diverse group of psychiatric patients who have been
      hospitalized, and none has done so in the southern US where socioeconomic
      inequality is high. METHODS: In this retrospective study, medical records from
      113 patients hospitalized for psychiatric illness were retrieved and analyzed.
      Vitamin D status in this population was estimated, along with any patterns of
      association between deficiency and risk factors. RESULTS: The vast majority of
      patients hospitalized for psychiatric illness in this biracial, low-income sample
      had either insufficient or deficient vitamin D levels. African-American patients
      had lower levels of vitamin D than Caucasian patients. DISCUSSION: Our findings
      demonstrate that hospitalized psychiatric patients are at increased risk for
      vitamin D deficiency and in particular low-income, African-American populations.
      These results suggest that vitamin D should be assessed and therapy considered at
      the initiation of psychiatric hospitalizations.

PMID- 27895489
TI  - Health provider experiences with galactagogues to support breastfeeding: a cross
      sectional survey.
AB  - BACKGROUND: Exclusive breastfeeding for infants up to 6 months is widely
      recommended, yet breastfeeding rates are relatively low in the US. The most
      common reason women stop breastfeeding early is a perceived insufficiency of
      milk. Galactagogues are herbal and pharmaceutical products that can help increase
      milk supply; however, data on their efficacy and safety is limited. Lactation
      consultants, obstetricians, and other health providers are an important point of
      contact for breastfeeding women experiencing challenges with lactation. This
      study explored providers' perceptions, experiences, and practices in relation to
      galactagogue recommendation. METHOD: A cross-sectional survey was conducted among
      a convenience sample of English-speaking health providers in the US who counsel
      breastfeeding women and their infants. RESULTS: More than 70% of respondents
      reported to recommend galactagogues. The most frequently recommended galactagogue
      was fenugreek with respondents indicating that they recommend it either 'always'
      (8.5%) or 'most of the time' (14.9%) and 'sometimes' (46.8%). More than 80% of
      the respondents indicated that galactagogues were useful for their clients and
      only one-third reported side effects. Reasons for refraining from recommending
      galactagogues were insufficient evidence of its efficacy and safety. Respondents
      reported a wide variety of sources of information used for their own education
      about galactagogues. DISCUSSION: Despite little evidence regarding safety and
      efficacy, some galactagogues are widely recommended and often perceived to be
      useful. However, concerns about their efficacy and safety remain. In order to
      assure both providers and users about safety and efficacy, more robust studies as
      well as better pharmacovigilance systems are needed.

PMID- 27895487
TI  - Combination therapy with lercanidipine and enalapril in the management of the
      hypertensive patient: an update of the evidence.
AB  - Hypertension is an important risk factor for premature death as it increases the
      probability of stroke, myocardial infarction, and heart failure. Antihypertensive
      drugs can decrease cardiovascular (CV) morbidity and mortality. The majority of
      hypertensive patients need more than one antihypertensive agent to attain blood
      pressure (BP) targets. Monotherapy can effectively reduce BP only in 20%-40% of
      patients. Multiple mechanisms including increased peripheral vascular resistance,
      increased cardiac work, and hypervolemia are involved in the pathogenesis of
      hypertension. Targeting multiple pathways may more potently reduce BP. Increasing
      the dose of a single agent in many cases does not provide the expected BP
      lowering effect because the underlying mechanism of the BP increase is either
      different or already corrected with the lower dose. Moreover, drugs acting on
      different pathways may have synergistic effects and thus better control
      hypertension. It is well known that diuretics enhance the actions of renin
      angiotensin aldosterone system and activate it as a feedback to the reduced
      circulated blood volume. The addition of a renin-angiotensin aldosterone system
      blocker to a diuretic may more effectively reduce BP because the system is
      upregulated. Reducing the maximal dose of an agent may also reduce possible side
      effects if they are dose dependent. The increased prevalence of peripheral edema
      with higher doses of calcium channel blockers (CCBs) is reduced when renin
      angiotensin aldosterone system blockers are added to CCBs through vein dilation.
      The effectiveness of the combination of enalapril with lercanidipine in reducing
      BP, the safety profile, and the use of the combination of angiotensin-converting
      enzyme inhibitors with CCBs in clinical trials with excellent CV hard end point
      outcomes make this combination a promising therapy in the treatment of
      hypertension.

PMID- 27895490
TI  - Paxillin functions as an oncogene in human gliomas by promoting cell migration
      and invasion.
AB  - BACKGROUND: Paxillin is implicated in tumorigenesis, progression and aggressive
      phenotypes of various malignancies, highlighting its functions in cellular
      adhesion, migration and survival. However, the roles of paxillin in human gliomas
      remain unclear. The aim of this study was to evaluate the clinical implication of
      paxillin expression in patients with gliomas and its biological function in
      glioma cells. PATIENTS AND METHODS: Expression levels of paxillin gene and
      protein, respectively, were detected by quantitative real-time reverse
      transcription polymerase chain reaction, Western blot and immunohistochemistry
      analyses in 120 pairs of glioma and matched nontumorous brain tissues. The
      associations between paxillin expression and various histopathological features
      of glioma patients were also statistically evaluated. Then, the functions of
      paxillin in cell migration and invasion of glioma cell lines were determined by
      transwell assays in vitro. RESULTS: The expression levels of both paxillin gene
      and protein in glioma tissues were markedly higher than those in matched
      nontumorous brain tissues. Notably, paxillin overexpression was significantly
      associated with the grade of malignancy (P<0.05). Moreover, the enforced
      expression of paxillin promoted the migration and invasion of glioma cells, while
      the loss of paxillin expression efficiently suppressed cell migration and
      invasion of glioma cell lines. CONCLUSION: Our data suggest that paxillin may
      function as an oncogene and its overexpression may be closely correlated with
      tumor progression of human gliomas by modulating tumor cell motility, implying
      the potential of paxillin as a new therapeutic target for glioma intervention.

PMID- 27895491
TI  - Comparison of internal target volumes defined on 3-dimensional, 4-dimensonal, and
      cone-beam CT images of non-small-cell lung cancer.
AB  - PURPOSE: The purpose of this study was to compare the positional and volumetric
      differences of internal target volumes defined on three-dimensional computed
      tomography (3DCT), four-dimensional CT (4DCT), and cone-beam CT (CBCT) images of
      non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty-one patients
      with NSCLC sequentially underwent 3DCT and 4DCT simulation scans of the thorax
      during free breathing. The first CBCT was performed and registered to the
      planning CT using the bony anatomy registration during radiotherapy. The gross
      tumor volumes were contoured on the basis of 3DCT, maximum intensity projection
      (MIP) of 4DCT, and CBCT. CTV3D (clinical target volume), internal target volumes,
      ITVMIP and ITVCBCT, were defined with a 7 mm margin accounting for microscopic
      disease. ITV10 mm and ITV5 mm were defined on the basis of CTV3D: ITV10 mm with a
      5 mm margin in left-right (LR), anterior-posterior (AP) directions and 10 mm in
      cranial-caudal (CC) direction; ITV5 mm with an isotropic internal margin (IM) of
      5 mm. The differences in the position, size, Dice's similarity coefficient (DSC)
      and inclusion relation of different volumes were evaluated. RESULTS: The median
      size ratios of ITV10 mm, ITV5 mm, and ITVMIP to ITVCBCT were 2.33, 1.88, and
      1.03, respectively, for tumors in the upper lobe and 2.13, 1.76, and 1.1,
      respectively, for tumors in the middle-lower lobe. The median DSCs of ITV10 mm,
      ITV5 mm, ITVMIP, and ITVCBCT were 0.6, 0.66, and 0.83 for all patients. The
      median percentages of ITVCBCT not included in ITV10 mm, ITV5 mm, and ITVMIP were
      0.1%, 1.63%, and 15.21%, respectively, while the median percentages of ITV10 mm,
      ITV5 mm, and ITVMIP not included in ITVCBCT were 57.08%, 48.89%, and 20.04%,
      respectively. CONCLUSION: The use of the individual ITV derived from 4DCT merely
      based on bony registration in radiotherapy may result in a target miss. The ITVs
      derived from 3DCT with isotropic margins have a good coverage of the ITV from
      CBCT, but the use of those would result in a high proportion of normal tissue
      being irradiated unnecessarily.

PMID- 27895492
TI  - MicroRNA-29a plays a suppressive role in non-small cell lung cancer cells via
      targeting LASP1.
AB  - MicroRNA (miR)-29a has been implicated in non-small cell lung cancer (NSCLC), but
      the mechanism remains largely unclear. LASP1, a cAMP- and cGMP-dependent
      signaling protein, was recently found to promote proliferation and aggressiveness
      in NSCLC. However, the regulatory mechanism of LASP1 expression in NSCLC, as well
      as the relationship between LASP1 and miR-29a, has never been previously studied.
      In this study, we found that miR-29a was remarkably downregulated and low
      expression of miR-29a was associated with the malignant progression of NSCLC.
      Moreover, the expression of LASP1 was markedly increased in NSCLC tissues and
      cell lines. Bioinformatics analysis and luciferase reporter assay data further
      identified LASP1 as a target gene of miR-29a, and the expression of LASP1 was
      negatively mediated by miR-29a at the post-transcriptional level in NSCLC cells.
      Overexpression of miR-29a reduced the proliferation, migration, and invasion of
      NSCLC cells, just as the effects of LASP1 knockdown. Moreover, overexpression of
      LASP1 attenuated the suppressive effect of miR-29a on the malignant phenotypes of
      NSCLC cells. In addition, upregulation of miR-29a decreased the growth of A549
      cells in nude mice and protected the animals from tumor-induced death. Therefore,
      we demonstrate that miR-29a plays a suppressive role in NSCLC via targeting
      LASP1, suggesting that the miR-29a/LASP1 axis may become a promising therapeutic
      target for NSCLC.

PMID- 27895493
TI  - CT-diagnosed severe skull base bone destruction predicts distant bone metastasis
      in early N-stage nasopharyngeal carcinoma.
AB  - Bone metastasis is the most frequent type of distant metastasis in nasopharyngeal
      carcinoma (NPC). In this study, we investigated the correlation between the skull
      base bone destruction and the distant bone metastasis in patients with NPC. A
      total of 449 cases with NPC who were diagnosed and had definitive radiotherapy
      from 2001 to 2006 were enrolled in this study. The skull base bone destruction
      was diagnosed by computed tomography (CT) in all cases, and 191 patients also
      underwent magnetic resonance imaging scan. Kaplan-Meier method was adopted to
      perform the univariate analysis; Cox regression model was used to perform
      multivariate analysis to determine whether the skull base bone destruction when
      diagnosed by CT was an independent impact factor of the distant bone metastases.
      The group with skull base bone destruction had a distant bone metastases rate of
      9.0% (14/155), whereas the group without skull base bone destruction had rate of
      4.1% (12/294). The multivariate analysis showed that the skull base bone
      destruction, when diagnosed by CT, was an independent impact factor of the
      distant bone metastases-free survival in the early N-staging cases, but was not
      an independent impact factor when diagnosed by MRI. The skull base bone
      destruction diagnosed by CT in patients with NPC had predictive value for the
      distant bone metastases, especially for the early N-staging cases.

PMID- 27895488
TI  - Advances in the management of heart failure: the role of ivabradine.
AB  - A high resting heart rate (>=70-75 b.p.m.) is a risk factor for patients with
      heart failure (HF) with reduced ejection fraction (EF), probably in the sense of
      accelerated atherosclerosis, with an increased morbidity and mortality. Beta
      blockers not only reduce heart rate but also have negative inotropic and blood
      pressure-lowering effects, and therefore, in many patients, they cannot be given
      in the recommended dose. Ivabradine specifically inhibits the pacemaker current
      (funny current, If) of the sinoatrial node cells, resulting in therapeutic heart
      rate lowering without any negative inotropic and blood pressure-lowering effect.
      According to the European Society of Cardiology guidelines, ivabradine should be
      considered to reduce the risk of HF hospitalization and cardiovascular death in
      symptomatic patients with a reduced left ventricular EF <=35% and sinus rhythm
      >=70 b.p.m. despite treatment with an evidence-based dose of beta-blocker or a
      dose below the recommended dose (recommendation class "IIa" = weight of
      evidence/opinion is in favor of usefulness/efficacy: "should be considered";
      level of evidence "B" = data derived from a single randomized clinical trial or
      large nonrandomized studies). Using a heart rate cutoff of >= 75 b.p.m., as
      licensed by the European Medicines Agency, treatment with ivabradine 5-7.5 mg
      b.i.d. reduces cardiovascular mortality by 17%, HF mortality by 39% and HF
      hospitalization rate by 30%. A high resting heart rate is not only a risk factor
      in HF with reduced EF but also at least a risk marker in HF with preserved EF, in
      acute HF and also in special forms of HF. In this review, we discuss the proven
      role of ivabradine in the validated indication "HF with reduced EF" together with
      interesting preliminary findings, and the potential role of ivabradine in
      further, specific forms of HF.

PMID- 27895494
TI  - ERCC1 and XRCC1 but not XPA single nucleotide polymorphisms correlate with
      response to chemotherapy in endometrial carcinoma.
AB  - Our study aimed to investigate the correlation between single nucleotide
      polymorphisms of ERCC1/XRCC1/XPA genes and postoperative chemotherapy efficacy
      and prognosis of endometrial carcinoma. Our study included 108 patients with
      endometrial carcinoma and 100 healthy participants. ERCC1 rs11615/XRCC1
      rs25487/XPA rs1800975 gene polymorphisms were detected by polymerase chain
      reaction-restriction fragment length polymorphism. Then the chemotherapy efficacy
      and toxic effects of the patients were assessed. The genotype and allele
      frequency of ERCC1 rs11615/XRCC1 rs25487 in the case group were significantly
      different from that in the control group (all P<0.05). The patients with AA + GA
      in ERCC1 rs11615 had an increased risk of endometrial carcinoma than those with
      GG, and the risk of endometrial carcinoma for patients with AA + GA was also
      higher in comparison with patients with GG genotype in XRCC1 rs25487 (all
      P<0.05). GG on both ERCC1 rs11615/XRCC1 rs25487 had a higher effective rate of
      chemotherapy than GA + AA (all P<0.05). ERCC1 rs11615/XRCC1 rs25487 gene
      polymorphisms were linked with toxic effects in liver, kidney, and nervous
      system. ERCC1 rs11615/XRCC1 rs25487, muscular invasion, and tumor stage were
      independent risk factors for the prognosis of endometrial carcinoma (all P<0.05).
      However, no significant associations were observed between XPA rs1800975
      polymorphism and chemotherapy efficacy and prognosis of endometrial carcinoma
      (all P>0.05). These results indicated that ERCC1 and XRCC1 but not XPA
      polymorphisms correlate with response to chemotherapy in endometrial carcinoma.

PMID- 27895495
TI  - Predictive values of diffusion-weighted imaging and perfusion-weighted imaging in
      evaluating the efficacy of transcatheter arterial chemoembolization for
      hepatocellular carcinoma.
AB  - This study explored the predictive values of diffusion-weighted imaging (DWI) and
      perfusion-weighted imaging (PWI) in evaluating the efficacy of transcatheter
      arterial chemoembolization (TACE) for patients with hepatocellular carcinoma
      (HCC). A total of 118 HCC patients treated with TACE were selected from April
      2013 to November 2015. T1-weighted imaging (T1WI)/T2-weighted imaging (T2WI),
      DWI, and PWI were performed on all patients before and after TACE. Efficacy was
      evaluated according to modified Response Evaluation Criteria in Solid Tumors 1.1.
      Receiver operating characteristic curve was used to evaluate the diagnostic power
      of quantitative DWI and PWI parameters in evaluating the efficacy of TACE for HCC
      patients. Among the 118 HCC patients, there were 17 cases (14.4%) with complete
      response, 50 cases (42.4%) with partial response, 28 cases (23.7%) with stable
      disease, and 23 cases (19.5%) with progressive disease. There were 67 patients in
      the effective group (complete response + partial response) and 51 patients in the
      ineffective group (stable disease + progressive disease). Before TACE, there were
      significant differences in maximum tumor diameter (MTD), apparent diffusion
      coefficient (ADC), slow ADC (Dslow), fast ADC (Dfast), transfer constant of
      vessel at the maximum level (Ktrans), and rate constant of backflux (Kep) between
      the effective and ineffective groups (all P<0.05). After TACE, the effective
      group exhibited lower MTD, Dfast, and Kep and higher ADC and Dslow than the
      ineffective group (all P<0.05). Tumor regression rate negatively correlated with
      MTD, Ktrans, Kep, and Dfast but positively correlated with ADC and Dslow.
      Receiver operating characteristic curve analysis suggested that the area under
      the curve of ADC, Dslow, Dfast, Ktrans, and Kep were 0.869, 0.833, 0.812, 0.802,
      and 0.809, respectively. In conclusion, these results suggest that quantitative
      DWI and PWI parameters might be useful in evaluating the efficacy of TACE in the
      treatment of HCC patients.

PMID- 27895496
TI  - Identification of lncRNA FAM83H-AS1 as a novel prognostic marker in luminal
      subtype breast cancer.
AB  - BACKGROUND: Luminal subtype breast cancer accounts for a predominant number of
      breast cancers. Considering the heterogeneity of the disease, it is urgent to
      develop novel biomarkers to improve risk stratification and optimize therapy
      choices. Long non-coding RNA (lncRNA) represents an emerging and understudied
      class of transcripts that play a significant role in cancer biology. Growing
      knowledge of cancer-associated lncRNAs contributes to the development of
      molecular markers for prognosis evaluation and gene therapy. MATERIALS AND
      METHODS: Three pairs of primary luminal subtype breast cancer tissues and
      adjacent non-cancerous tissues were collected and sequenced. EBseq algorithm was
      used to identify differentially expressed lncRNAs. RNA sequencing data from The
      Cancer Genome Atlas (TCGA) database were used to validate the robustness of our
      RNA-seq results. Kaplan-Meier and Cox regression analyses were utilized to assess
      the association between the lncRNAs and overall survival of patients in TCGA
      cohort. RESULTS: A total of 796 lncRNAs were significantly dysregulated in
      luminal subtype breast cancer, including 436 upregulated and 360 downregulated
      lncRNAs. Among them, FAM83H antisense RNA 1 (FAM83H-AS1) was the most upregulated
      lncRNA, whereas GSN antisense RNA 1 (GSN-AS1) was the most downregulated lncRNA.
      Moreover, we proved that the high expression level of FAM83H-AS1 indicated
      unfavorable prognosis not only in luminal subtype breast cancer but also in all
      subtype breast cancers. To the best of our knowledge, this is the first report
      indicating that FAM83H-AS1 was involved in luminal subtype breast cancer and was
      an independent prognostic indicator. CONCLUSION: Our study provides a rich
      resource to the research community for further identifying lncRNAs with
      diagnostic and therapeutic potentials and exploring biological function of
      lncRNAs in luminal subtype breast cancer.

PMID- 27895497
TI  - MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma
      cells via targeting NRP1.
AB  - MicroRNAs (miRs) are a class of small noncoding RNAs that negatively regulate the
      gene expression by directly binding to the 3' untranslated region of their target
      mRNA, thus resulting in mRNA degradation or translational repression. miR-9 has
      recently been demonstrated to play a role in the development and progression of
      malignant melanoma (MM), but the regulatory mechanism of miR-9 in the malignant
      phenotypes of MM still remains largely unknown. In this study, a total of 73
      pairs of MM tissues and adjacent normal tissues were collected. Real-time reverse
      transcription polymerase chain reaction and Western blot were used to detect the
      mRNA and protein expression of miR-9. MTT assay, wound healing assay, and
      transwell assay were conducted to determine the cell proliferation, migration,
      and invasion. Luciferase reporter assay was used to determine the targeting
      relationship between miR-9 and NRP1. Our data demonstrated that miR-9 expression
      was significantly downregulated in MM tissues compared with that in adjacent
      normal tissues. The decreased miR-9 level was significantly associated with the
      tumor stage and metastasis of MM. We also found that the expression level of miR
      9 was decreased in MM cell lines (G361, B16, A375, and HME1) compared with normal
      skin HACAT cells. Ectopic expression of miR-9 led to a significant decrease in
      the ability of proliferation, migration, and invasion in A375 cells. NRP1 was
      further identified as a direct target gene of miR-9, and the protein expression
      of NRP1 was negatively regulated by miR-9 in A375 cells. Furthermore,
      overexpression of NRP1 reversed the suppressive effects of miR-9 on the malignant
      phenotypes of A375 cells. In vivo study revealed that miR-9 overexpression
      decreased the tumor growth, while overexpression of NRP1 increased MM growth. In
      summary, our findings suggest that the miR-9/NRP1 axis may serve as a potential
      target for the treatment of MM.

PMID- 27895498
TI  - Meta-analysis of outcomes of patients with stage IV colorectal cancer managed
      with chemotherapy/radiochemotherapy with and without primary tumor resection.
AB  - BACKGROUND: Colorectal cancer is the third leading cause of death worldwide.
      Currently, novel chemotherapeutic agents are first-line therapy for unresectable
      stage IV colorectal cancer, while benefits of noncurative primary tumor resection
      in advanced disease remain debatable. OBJECTIVE: This meta-analysis evaluated
      outcomes of patients with unresectable stage IV colorectal cancer receiving
      systemic chemotherapy with or without primary tumor resection. MATERIALS AND
      METHODS: A database search of PubMed and Cochrane Library databases identified
      167 studies that were screened for relevance. After 119 were excluded, 48 were
      assessed for eligibility and 26 were included for meta-analysis, including 24
      retrospective studies, one prospective study, and one randomized, controlled
      trial. Extracted data included patient demographics (age, sex), clinical data
      (tumor stage, metastasis), targeted therapy agents, and surgical data
      (with/without tumor resection). Patients' overall and progression-free survival
      was compared between groups with/without primary tumor resection. RESULTS: The 26
      studies included 43,903 patients with colorectal cancer, with 29,639 receiving
      chemotherapy/radiotherapy plus primary tumor resection, and 14,264 managed
      medically with chemotherapy/chemoradiotherapy alone without primary tumor
      resection. Patients receiving primary tumor resection plus
      chemotherapy/radiotherapy had longer overall survival (hazard ratio [HR 0.59],
      95% confidence interval [CI] 0.51-0.68; P<0.001), with significant differences in
      overall survival between patients with and without primary tumor resection (HR
      0.58, 95% CI 0.49-0.68; P<0.001). Longer overall survival was also found among
      patients receiving primary tumor resection who were treated with
      bevacizumab/cetuximab targeted therapy agents (HR 0.63, 95% CI 0.46-0.86;
      P=0.003). Patients from three studies who received primary tumor resection had
      longer progression-free survival (HR 0.73, 95% CI 0.58-0.91; P=0.005). Results
      are limited by retrospective data, inconsistent complications data, and
      publication bias. CONCLUSION: Study results support primary tumor resection in
      stage IV colorectal cancer, but significant biases in studies suggest that
      randomized trials are warranted to confirm findings.

PMID- 27895499
TI  - Lrig1 is a positive prognostic marker in hepatocellular carcinoma.
AB  - BACKGROUND: The prevalence of hepatocellular carcinoma (HCC) is increasing
      worldwide. As a consequence, there is an urgent need for identifying molecular
      markers of HCC development and progression. Recently, several studies have
      suggested that the Lrig1 may have prognostic implications in various cancer
      types, but its clinical value in HCC is not well evaluated. MATERIALS AND
      METHODS: In this study, the expression level of Lrig1 was examined in 133 HCC
      tissues and adjacent normal tissues by immunohistochemistry. Furthermore,
      potential associations between Lrig1 expression and the carcinoma clinical
      parameters were investigated, including recurrence and survival rate. We silenced
      the Lrig1 in the normal liver cell line (LO2) and liver cancer cell line (Hep-G2)
      in vitro by the small interference RNA and detected its influence on
      proliferation, migration, and invasion. RESULTS: The expression of Lrig1 was
      significantly downregulated in liver cancer tissues and cell lines, and its
      expression levels were related to tumor size, tumor-node-metastasis staging and
      tumor recurrence. Furthermore, analysis of 6-year survival of 133 HCC patients
      showed that those with stronger Lrig1 expression had significantly longer overall
      survival time than those with weaker Lrig1 expression. In addition, decreased
      expression of Lrig1 in vitro promoted the growth, migration, or invasion of
      normal liver cells and cancer cells. CONCLUSION: Our findings demonstrate that
      Lrig1 could serve as a potential marker in the prognosis of patients with HCC. We
      also revealed that Lrig1 might be involved in the metastatic progression of liver
      cancer. However, its clinical value should be further investigated in the future.

PMID- 27895500
TI  - Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage
      colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma:
      subanalysis of the Phase III OPTiM trial.
AB  - OBJECTIVES: Talimogene laherparepvec is the first oncolytic immunotherapy to
      receive approval in Europe, the USA and Australia. In the randomized, open-label
      Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly
      improved durable response rate (DRR) versus granulocyte-macrophage colony
      stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB-IVM1c
      melanoma. The median overall survival (OS) was longer versus GM-CSF in patients
      with earlier-stage melanoma (IIIB-IVM1a). Here, we report a detailed subgroup
      analysis of the OPTiM study in patients with IIIB-IVM1a disease. PATIENTS AND
      METHODS: The patients were randomized (2:1 ratio) to intralesional talimogene
      laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response
      rate (ORR), OS, safety, benefit-risk and numbers needed to treat. Descriptive
      statistics were used for subgroup comparisons. RESULTS: Among 249 evaluated
      patients with stage IIIB-IVM1a melanoma, DRR was higher with talimogene
      laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001). ORR was also
      higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001), and 27
      patients in the talimogene laherparepvec arm had a complete response, compared
      with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted
      adverse events (AE) and serious AEs were similar with both treatments.
      CONCLUSION: The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma
      (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR
      and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene
      laherparepvec was well tolerated.

PMID- 27895501
TI  - A FISH-based method for assessment of HER-2 amplification status in breast cancer
      circulating tumor cells following CellSearch isolation.
AB  - INTRODUCTION: Amplification of the HER-2/neu (HER-2) proto-oncogene occurs in 10%
      15% of primary breast cancer, leading to an activated HER-2 receptor, augmenting
      growth of cancer cells. Tumor classification is determined in primary tumor
      tissue and metastatic biopsies. However, malignant cells tend to alter their
      phenotype during disease progression. Circulating tumor cell (CTC) analysis may
      serve as an alternative to repeated biopsies. The Food and Drug Administration
      approved CellSearch system allows determination of the HER-2 protein, but not of
      the HER-2 gene. The aim of this study was to optimize a fluorescence in situ
      hybridization (FISH)-based method to quantitatively determine HER-2 amplification
      in breast cancer CTCs following CellSearch-based isolation and verify the method
      in patient samples. METHODS: Using healthy donor blood spiked with human
      epidermal growth factor receptor 2 (HER-2)-positive breast cancer cell lines,
      SKBr-3 and BT-474, and a corresponding negative control (the HER-2-negative MCF-7
      cell line), an in vitro CTC model system was designed. Following isolation in the
      CellSearch system, CTC samples were further enriched and fixed on microscope
      slides. Immunocytochemical staining with cytokeratin and 4',6-diamidino-2'
      phenylindole dihydrochloride identified CTCs under a fluorescence microscope. A
      FISH-based procedure was optimized by applying the HER2 IQFISH pharmDx assay for
      assessment of HER-2 amplification status in breast cancer CTCs. RESULTS: A method
      for defining the presence of HER-2 amplification in single breast cancer CTCs
      after CellSearch isolation was established using cell lines as positive and
      negative controls. The method was validated in blood from breast cancer patients
      showing that one out of six patients acquired CTC HER-2 amplification during
      treatment against metastatic disease. CONCLUSION: HER-2 amplification status of
      CTCs can be determined following CellSearch isolation and further enrichment.
      FISH is superior to protein assessment of HER-2 status in predicting response to
      HER-2-targeted immunotherapy in breast cancer patients. This assay has the
      potential of identifying patients with a shift in HER-2 status who may benefit
      from treatment adjustments.

PMID- 27895503
TI  - Methotrexate induces DNA damage and inhibits homologous recombination repair in
      choriocarcinoma cells.
AB  - OBJECTIVE: The objective of this study was to investigate the mechanism of
      sensitivity to methotrexate (MTX) in human choriocarcinoma cells regarding DNA
      damage response. METHODS: Two choriocarcinoma cancer cell lines, JAR and JEG-3,
      were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX
      resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical
      adenocarcinoma cell line Hela served as controls. Cell viability assay was
      carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was
      evaluated by comet assay. Quantitative reverse transcription polymerase chain
      reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The
      protein levels of gammaH2AX, RAD 51 and p53 were analyzed by Western blot.
      RESULTS: Remarkable DNA strand breaks were observed in MTX-sensitive cell lines
      (JAR, JEG-3 and MG63) but not in MTX-resistant cancer cells (A2780 and Hela)
      after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of
      homologous recombination (HR) repair gene RAD51 was dramatically suppressed by
      MTX in a dose- and time-dependent manner, accompanied with the increase in p53.
      CONCLUSION: The MTX-induced DNA strand breaks accompanied by deficiencies in HR
      repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma.

PMID- 27895502
TI  - Human papillomavirus as a potential risk factor for gastric cancer: a meta
      analysis of 1,917 cases.
AB  - BACKGROUND: Human papillomaviruses (HPVs) are causally associated with the
      tumorigenesis of several classes of cancers. However, the prevalence of HPV in
      gastric cancer (GC) has not yet been systematically reviewed. Hence, a meta
      analysis was conducted to estimate the HPV prevalence in patients with GC, and
      its potential etiologic significance was assessed. METHODS: The pooled HPV
      prevalence and 95% confidence intervals (CIs) were estimated among all GC
      patients. Heterogeneity was described by using the I2 statistic. Sources of
      heterogeneity were explored by meta-regression and stratified analyses. The meta
      influence was applied to evaluate the influence of a single study on the pooled
      estimates. Odds ratios (ORs) and 95% CIs were computed for case-control studies.
      For research providing clinicopathological parameters of age, sex, pathological,
      differentiated, and clinical stages, and HPV subtypes, the corresponding pooled
      ORs and 95% CIs were also calculated. RESULTS: Thirty studies were included in
      the current meta-analysis, involving 1,917 patients with GC and 576 controls. The
      pooled HPV prevalence was 28.0% (95% CI: 23.2%, 32.7%) among all the patients
      with GC, and the I2 was 96.9% (P<0.001). A pooled OR of 7.388 (95% CI: 3.876,
      14.082) was achieved based on 15 case-control studies (I2=56.7%, P=0.004).
      Moreover, the HPV prevalence was significantly higher in patients from China than
      in those from non-Chinese regions (31% vs 9%, I2=95.0%, P<0.001). The pooled
      prevalence of HPV16 was 21% in GC tissues, and the pooled prevalence of HPV18 was
      7% with an OR of 3.314 (95% CI =1.617, 6.792). HPV16 was 3 times more frequently
      detected than HPV18. CONCLUSION: HPV could play a potential role in the
      pathogenesis of GC. A causal relationship can be confirmed only by detecting HPV
      in the cells of GC precursor lesions (gastric dysplasia or adenoma). In addition,
      this study might be beneficial for expounding the potential etiologic
      significance of molecular mechanism of gastric tumorigenesis and providing
      opinions regarding precautionary measures.

PMID- 27895504
TI  - Deferred radiotherapy and upfront procarbazine-ACNU-vincristine administration
      for 1p19q codeleted oligodendroglial tumors are associated with favorable outcome
      without compromising patient performance, regardless of WHO grade.
AB  - Recently updated phase III trials revealed the favorable effect of add-on
      procarbazine-lomustine-vincristine chemotherapy (CT) to radiotherapy (RT) in
      treating anaplastic oligodendrogliomas with 1p19q codeletion (codel). However,
      the underlying rationality of deferring RT and upfront CT administration for
      these tumors is yet to be elucidated. Here, we retrospectively analyzed the long
      term outcome of our case series with oligodendroglial tumors treated with
      deferred RT and upfront procarbazine+nimustine+vincristine (PAV) in the
      introduction administration. We enrolled 36 patients with newly diagnosed
      oligodendroglial tumors (17, grade II and 19, grade III) treated during 1999-2012
      and followed up for a median period of 69.0 months. Their clinical and genetic
      prognostic factors were analyzed, and progression-free survival, overall survival
      (OS), and deterioration-free survival (DFS) were evaluated. Regardless of the WHO
      grade, the 25 patients with 1p19q codel tumors never received RT initially, and
      of these 25, 23 received PAV treatment upfront. The 75% OS of patients with 1p19q
      codel tumor was 135.3 months (did not reach the median OS), indicating a
      favorable outcome. Multivariate analysis revealed that IDH mutation and 1p19q,
      not WHO grade, are independent prognostic factors; furthermore, IDH and 1p19q
      status stratified the cohort into 3 groups with significantly different OS. The
      DFS explained the prolonged survival without declining performance in patients
      with both grade II and III 1p19q codel tumors. Deferred RT and upfront PAV
      treatment for 1p19q codel oligodendrogliomas were associated with favorable
      outcomes without compromising performance status, regardless of WHO grade.

PMID- 27895505
TI  - Evaluating increased resource use in fibromyalgia using electronic health
      records.
AB  - OBJECTIVE: The management of fibromyalgia (FM), a chronic musculoskeletal
      disease, remains challenging, and patients with FM are often characterized by
      high health care resource utilization. This study sought to explore potential
      drivers of all-cause health care resource utilization and other factors
      associated with high resource use, using a large electronic health records (EHR)
      database to explore data from patients diagnosed with FM. METHODS: This was a
      retrospective analysis of de-identified EHR data from the Humedica database.
      Adults (>=18 years) with FM were identified based on >=2 International
      Classification of Diseases, Ninth Revision codes for FM (729.1) >=30 days apart
      between January 1, 2008 and December 31, 2012 and were required to have evidence
      of >=12 months continuous care pre- and post-index; first FM diagnosis was the
      index event; 12-month pre- and post-index reporting periods. Multivariable
      analysis evaluated relationships between variables and resource utilization.
      RESULTS: Patients were predominantly female (81.4%), Caucasian (87.7%), with a
      mean (standard deviation) age of 54.4 (14.8) years. The highest health care
      resource utilization was observed for the categories of "medication orders" and
      "physician office visits," with 12-month post-index means of 21.2 (21.5) drug
      orders/patient and 15.1 (18.1) office visits/patient; the latter accounted for
      73.3% of all health care visits. Opioids were the most common prescription
      medication, 44.3% of all patients. The chance of high resource use was
      significantly increased (P<0.001) 26% among African-Americans vs Caucasians and
      for patients with specific comorbid conditions ranging from 6% (musculoskeletal
      pain or depression/bipolar disorder) to 21% (congestive heart failure). Factors
      significantly associated with increased medications ordered included being female
      (P<0.001) and specific comorbid conditions (P<0.05). CONCLUSION: Physician office
      visits and pharmacotherapy orders were key drivers of all-cause health care
      utilization, with demographic factors, opioid use, and specific comorbidities
      associated with resource intensity. Health systems and providers may find their
      EHRs to be a useful tool for identifying and managing resource-intensive FM
      patients.

PMID- 27895506
TI  - Patient-reported financial barriers to adherence to treatment in neurology.
AB  - OBJECTIVE: Many effective medical therapies are available for treating
      neurological diseases, but these therapies tend to be expensive and adherence is
      critical to their effectiveness. We used patient-reported data to examine the
      frequency and determinants of financial barriers to medication adherence among
      individuals treated for neurological disorders. PATIENTS AND METHODS: Patients
      completed cross-sectional surveys on iPads as part of routine outpatient care in
      a neurology clinic. Survey responses from a 3-month period were collected and
      merged with administrative sources of demographic and clinical information (eg,
      insurance type). We explored the association between patient characteristics and
      patient-reported failure to refill prescription medication due to cost in the
      previous 12 months, termed here as "nonadherence". RESULTS: The population
      studied comprised 6075 adults who were presented between July and September 2015
      for outpatient neurology appointments. The mean age of participants was 56
      (standard deviation: 18) years, and 1613 (54%) were females. The patients who
      participated in the surveys (2992, 49%) were comparable to nonparticipants with
      respect to gender and ethnicity but more often identified English as their
      preferred language (94% vs 6%, p<0.01). Among respondents, 9.8% (n=265) reported
      nonadherence that varied by condition. These patients were more frequently
      Hispanic (16.7% vs 9.8% white, p=0.01), living alone (13.9% vs 8.9% cohabitating,
      p<0.01), and preferred a language other than English (15.3% vs 9.4%, p=0.02).
      CONCLUSION: Overall, the magnitude of financial barriers to medication adherence
      appears to vary across neurological conditions and demographic characteristics.

PMID- 27895507
TI  - Fc gamma receptors: glycobiology and therapeutic prospects.
AB  - Therapeutic antibodies hold great promise for the treatment of cancer and
      autoimmune diseases, and developments in antibody-drug conjugates and bispecific
      antibodies continue to enhance treatment options for patients. Immunoglobulin
      (Ig) G antibodies are proteins with complex modifications, which have a
      significant impact on their function. The most important of these modifications
      is glycosylation, the addition of conserved glycans to the antibody Fc region,
      which is critical for its interaction with the immune system and induction of
      effector activities such as antibody-dependent cell cytotoxicity, complement
      activation and phagocytosis. Communication of IgG antibodies with the immune
      system is controlled and mediated by Fc gamma receptors (FcgammaRs), membrane
      bound proteins, which relay the information sensed and gathered by antibodies to
      the immune system. These receptors are also glycoproteins and provide a link
      between the innate and adaptive immune systems. Recent information suggests that
      this receptor glycan modification is also important for the interaction with
      antibodies and downstream immune response. In this study, the current knowledge
      on FcgammaR glycosylation is discussed, and some insight into its role and
      influence on the interaction properties with IgG, particularly in the context of
      biotherapeutics, is provided. For the purpose of this study, other Fc receptors
      such as FcalphaR, FcepsilonR or FcRn are not discussed extensively, as IgG-based
      antibodies are currently the only therapeutic antibody-based products on the
      market. In addition, FcgammaRs as therapeutics and therapeutic targets are
      discussed, and insight into and comment on the therapeutic aspects of receptor
      glycosylation are provided.

PMID- 27895508
TI  - Multi-ethnic differences in HbA1c, blood pressure, and low-density-lipid
      cholesterol control among South Africans living with type 2 diabetes, after a 4
      year follow-up.
AB  - PURPOSE: Our study set out to examine if disparities in control of glycated
      hemoglobin (HbA1c), blood pressure (BP), and low-density-lipoprotein cholesterol
      (LDL-C) existed among an urban multi-ethnic cohort of South Africans, living with
      type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: This longitudinal,
      retrospective study consisted of 261 men and women with previously diagnosed T2DM
      who attended Charlotte Maxeke Johannesburg Academic Hospital, South Africa across
      two time periods 2009 and 2013. Demographic and clinical data were extracted from
      consecutive medical records. The primary outcome was to determine achievements in
      HbA1c, BP, and LDL-C among ethnic groups using evidence-based goals. RESULTS: The
      mean age of the cohort was 64 (+/-10.6) years, females represented 55%, and the
      self-reported diabetes duration was 16 (+/-10.6) years as at 2013. Black Africans
      (42.9%, n=112 of 261) were more likely to reach the HbA1c target (<7%) and less
      likely to have had retinopathy, nephropathy, or cardiovascular disease. Over two
      thirds of mixed-ancestry patients attained the BP target (<140/80 mmHg), while
      90.2% of Caucasians achieved LDL-C goals (<2.5 mmol/L). Overall, across the
      ethnic groups studied, we found that HbA1c control deteriorated over time,
      although BP levels remained the same and LDL-C levels drastically improved.
      CONCLUSION: There was poor control of HbA1c, BP, and LDL-C across all ethnic
      groups. Although a minority achieved recommended targets, some ethnic groups
      appeared to have worse control than others. Timely aggressive actions in
      particularly high-risk ethnic groups will prevent/delay the complications
      commonly associated with T2DM.

PMID- 27895509
TI  - Effects of fentanyl on pain and motor behaviors following a collagenase-induced
      intracerebral hemorrhage in rats.
AB  - PURPOSE: Intracerebral hemorrhage (IH) and cephalalgia are common consequences of
      traumatic brain injury. One of the primary obstacles for patient recovery is the
      paucity of treatments to support an appropriate analgesic protocol. The present
      study aimed to assess pain and motor behaviors following different doses of
      fentanyl on a rat model of IH. METHODS: Twenty-one male Sprague Dawley rats
      underwent a stereotaxic surgery to produce a collagenase-induced IH in the right
      caudoputamen nucleus. The control group (n=6) received saline subcutaneously
      (SC), and experimental groups received either 5 (n=6), 10 (n=6), or 20 (n=3)
      ug/kg of fentanyl SC, 2 hours following surgery and on 2 subsequent days. Only 3
      animals received 20 ug/kg because this dose caused catalepsy for 15-20 minutes
      following the injection. The rat grimace scale, a neurological examination,
      balance beam test, and rotarod test were performed for 5 consecutive days
      postoperatively to evaluate pain and motor performance. At the end of the
      experimentation, the brains were evaluated to determine hematoma volume, and the
      number of reactive astrocytes and necrotic neurons. RESULTS: When compared to
      controls, the grimace scale showed that 5 ug/kg fentanyl significantly alleviated
      pain on day 2 only (P<0.01) and that 10 ug/kg alleviated pain on days 1 (P<0.01),
      2 (P<0.001), and 3 (P<0.01). For the rotarod test, only the 10 ug/kg group showed
      significant decreases in performance on days 5 (P<0.05) and 6 (P<0.02). The
      neurological examination was not significantly different between the groups, but
      only the hopping test showed poor recuperation for the 5 and 10 ug/kg fentanyl
      group when compared to saline (P<0.01). No differences were found between the
      groups for the balance beam test, the histopathological results. CONCLUSION:
      Fentanyl, at a dose of 10 ug/kg SC, provides substantial analgesia following a
      collagenase-induced IH in rats; however, it can alter motor performance following
      analgesic treatments.

PMID- 27895510
TI  - The psychological profile of women presenting to a multidisciplinary clinic for
      chronic pelvic pain: high levels of psychological dysfunction and implications
      for practice.
AB  - OBJECTIVE: Chronic pelvic pain (CPP) is widely acknowledged as a common problem
      with significant consequences for those diagnosed with this condition. There is a
      lack of studies with good sample size that provide a comprehensive psychological
      profile of women presenting to specialist chronic pain clinics. Therefore, the
      objective of this study was to describe the psychological profile of a
      representative sample of women presenting with CPP at a tertiary referral center.
      DESIGN: This was a cross-sectional study. Women were asked to complete a
      questionnaire assessing symptoms of anxiety and depression, pain severity and
      interference, pain self-efficacy and catastrophizing beliefs, and sexual
      functioning. METHODS: One-hundred and seventy-five women with CPP were recruited
      when they attended their initial assessment at a specialist CPP clinic of the
      Royal Women's Hospital, a public hospital in Melbourne, Australia. RESULTS: Over
      75% of the participants had experienced pain for longer than 2 years. Fifty-three
      percent of women experienced either moderate or severe anxiety, and 26.7%
      experienced moderate-to-severe depression. There were strong correlations between
      depressive symptoms and pain interference, pain catastrophizing and self-efficacy
      beliefs. CONCLUSION: Our findings confirm previous evidence for high levels of
      psychological distress and functional impairment associated with this condition,
      and extend these findings by including measures that are highly relevant to
      treatment planning, such as thinking styles and pain self-efficacy. Therefore,
      treatment of this complex condition needs to be holistic, and a multidisciplinary
      approach is likely to be the best way to achieve this.

PMID- 27895511
TI  - Words that describe chronic musculoskeletal pain: implications for assessing pain
      quality across cultures.
AB  - BACKGROUND: People from different cultures who speak different languages may
      experience pain differently. This possible variability has important implications
      for evaluating the validity of pain quality measures that are directly translated
      into different languages without cultural adaptations. The aim of this study was
      to evaluate the impact of language and culture on the validity of pain quality
      measures by comparing the words that individuals with chronic pain from Nepal use
      to describe their pain with those used by patients from the USA. METHODS: A total
      of 101 individuals with chronic musculoskeletal pain in Nepal were asked to
      describe their pain. The rates of the different pain descriptor domains and
      phrases used by the Nepali sample were then compared to the published rates of
      descriptors used by patients from the USA. The content validity of commonly used
      measures for assessing pain quality was then evaluated. RESULTS: While there was
      some similarity between patients from Nepal and the USA in how they describe
      pain, there were also important differences, especially in how pain quality was
      described. For example, many patients from Nepal used metaphors to describe their
      pain. Also, the patients from Nepal often used a category of pain descriptor -
      which describes a physical state - not used by patients from the USA. Only the
      original McGill Pain Questionnaire was found to have content validity for
      assessing pain quality in patients from Nepal, although other existing pain
      quality measures could be adapted to be content valid by adding one or two
      additional descriptors, depending on the measure in question. CONCLUSION: The
      findings indicate that direct translations of measures that are developed using
      samples of patients from one country or culture are not necessarily content valid
      for use in other countries or cultures; some adaptations may be required in order
      for such measures to be most useful in new language and culture.

PMID- 27895512
TI  - Are another 5 years of adjuvant aromatase inhibitor therapy needed?

PMID- 27895513
TI  - Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells.
AB  - Resistance to antiestrogen therapy remains a significant problem in breast
      cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been
      correlated with increased rates of recurrence in estrogen receptor-positive (ER+)
      breast cancer patients, suggesting a role for ING4 in ER signaling. This study
      provides evidence that ING4 inhibits ER activity. ING4 overexpression increased
      the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation.
      ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose
      response of estrogen. These results indicated that ING4 functions as a
      noncompetitive inhibitor of estrogen signaling and may inhibit estrogen
      independent ER activity. Supportive of this, treatment with fulvestrant but not
      tamoxifen rendered T47D cells sensitive to hormone deprivation as did ING4
      overexpression. ING4 did not affect nuclear ERalpha protein expression, but
      repressed selective ER-target gene transcription. Taken together, these results
      demonstrated that ING4 inhibited estrogen-independent ER activity, suggesting
      that ING4-low breast tumors recur faster due to estrogen-independent ER activity
      that renders tamoxifen less effective. This study puts forth fulvestrant as a
      proposed therapy choice for patients with ING4-low ER+ breast tumors.

PMID- 27895514
TI  - Success rate in preterm uterine contraction inhibition with tocolytic agents in a
      tertiary care center.
AB  - OBJECTIVE: This study aims to assess the success rate of inhibiting preterm
      uterine contraction with tocolytic agents to delay delivery for at least 48 hours
      and risk factors of failure inhibition. MATERIALS AND METHODS: Between January
      2013 and July 2014, medical records of all singleton pregnant women between 24
      0/7 and 33 6/7 weeks of gestation with the diagnosis of preterm labor (with
      cervical dilatation) or threatened preterm labor (without cervical dilatation)
      who received tocolytic agents were reviewed. The success rate of preterm uterine
      contraction inhibition was accounted in patients with 48 hours delayed delivery.
      The risk factors of the inhibition failure and neonatal outcomes were also
      investigated in this study. RESULTS: Among 424 pregnant women diagnosed of
      preterm labor or threatened preterm labor, 103 singleton pregnant women met the
      study criteria. Overall success rate of preterm uterine contraction inhibition to
      prolong pregnancy for at least 48 hours was 86.4% (95% confidence interval [CI]:
      78.3, 92.3). However, the success rate among the threatened preterm labor group
      was 93.8% (95% CI: 88.3, 99.1) while the preterm labor group was 60.9% (95% CI:
      39.3, 82.4). The significant factor associated with inhibition failure was
      preterm labor (adjusted odds ratio 7.22; 95% CI: 1.99, 26.20). CONCLUSION: The
      success rate of preterm uterine contraction inhibition with tocolytic agents to
      delay delivery for at least 48 hours was high in threatened preterm labor and low
      in preterm labor. A significant risk factor for inhibition failure was the
      preterm uterine contraction with cervical change.

PMID- 27895515
TI  - Excellent response of infantile orbital hemangioma to propranolol.
AB  - Infantile hemangiomas are the most common vascular neoplasm that present in
      infancy, with more than half affecting the head and neck region. Periocularly,
      hemangiomas may be complicated by visual loss through induction of strabismal,
      deprivational, or anisometropic astigmatism. We report a case of a 5-year-old
      girl who presented with orbital hemangioma with potential risk of visual loss who
      had excellent response to propranolol.

PMID- 27895516
TI  - A prospective, observational study comparing the PK/PD relationships of generic
      Meropenem (Mercide(r)) to the innovator brand in critically ill patients.
AB  - INTRODUCTION: Clinicians' skepticism, fueled by evidence of inferiority of some
      multisource generic antimicrobial products, results in the underutilization of
      more cost-effective generics, especially in critically ill patients. The aim of
      this observational study was to demonstrate equivalence between the generic or
      comparator brand of meropenem (Mercide(r)) and the leading innovator brand
      (Meronem(r)) by means of an ex vivo technique whereby antimicrobial activity is
      used to estimate plasma concentration of the active moiety. METHODS: Patients
      from different high care and intensive care units were recruited for observation
      when prescribed either of the meropenem brands under investigation. Blood samples
      were collected over 6 hours after a 30 minute infusion of the different brands.
      Meropenem concentration curves were established against United States
      Pharmacopeia standard meropenem (Sigma-Aldrich) by using standard laboratory
      techniques for culture of Klebsiella pneumoniae. Patients' plasma samples were
      tested ex vivo, using a disc diffusion assay, to confirm antimicrobial activity
      and estimate plasma concentrations of the two brands. RESULTS: Both brands of
      meropenem demonstrated similar curves in donor plasma when concentrations in
      vials were confirmed. Patient-specific serum concentrations were determined from
      zones of inhibition against a standard laboratory Klebsiella strain ex vivo,
      confirming at least similar in vivo concentrations as the concentration curves
      (90% confidence interval) overlapped; however, the upper limit of the area under
      the curve for the ratio comparator/innovator exceeded the 1.25-point estimate,
      i.e., 4% higher for comparator meropenem. CONCLUSION: This observational, in
      practice study demonstrates similar ex vivo activity and in vivo plasma
      concentration time curves for the products under observation. Assay sensitivity
      is also confirmed. Current registration status of generic small molecules is in
      place. The products are therefore clinically interchangeable based on
      registration status as well as bioassay results, demonstrating sufficient overlap
      for clinical comfort. The slightly higher observed comparator meropenem
      concentration (4%) is still clinically acceptable due to the large therapeutic
      index and should ally fears of inferiority.

PMID- 27895517
TI  - Influence of curcumin on the pharmacodynamics and pharmacokinetics of gliclazide
      in animal models.
AB  - PURPOSE: Patients suffering from obesity-related diseases use multiple
      prescription drugs to control their condition, and it is therefore essential to
      determine the safety and efficacy of any combination. Gliclazide is one of the
      most commonly used drug of choice for treatment of type 2 diabetes, and curcumin
      is a widely used herbal supplement to counter obesity condition. The objective of
      this study was to investigate the effect of oral administration of curcumin on
      pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits to
      further evaluate the safety and effectiveness of this combination. METHODS:
      Influence of curcumin on the activity of gliclazide was determined by conducting
      single- and multiple-dose interaction studies in rats (normal and diabetic) and
      rabbits. Blood samples collected at predetermined time intervals from
      experimental animals were used for the estimation of glucose and insulin levels
      by using automated clinical chemistry analyzer and radioimmunoassay method,
      respectively. The insulin resistance and beta-cell function were determined by
      homeostasis model assessment. Additionally, serum gliclazide levels in rabbits
      were analyzed by high-performance liquid chromatography. RESULTS: Gliclazide
      showed peak reduction in blood glucose levels at 2 and 8 hours in rats and at 3
      hours in rabbits. This activity of gliclazide was not altered by single-dose
      treatment with curcumin. However, in multiple-dose interaction studies, samples
      analyzed from all time points showed subtle but significantly greater reduction
      in percent blood glucose ranging from 23.38% to 42.36% in normal rats, 27.63% to
      42.27% in diabetic rats, and 16.50% to 37.88% in rabbits. The pharmacokinetics of
      gliclazide was not altered by single- or multiple-dose curcumin treatments in
      rabbits. CONCLUSION: The interaction of curcumin with gliclazide up on multiple
      dose treatment was pharmacodynamic in nature, indicating the need for periodic
      monitoring of glucose levels and dose adjustment as necessary when this
      combination is prescribed to obese patients.

PMID- 27895518
TI  - Single-leg squats can predict leg alignment in dancers performing ballet
      movements in "turnout".
AB  - The physical assessments used in dance injury surveillance programs are often
      adapted from the sports and exercise domain. Bespoke physical assessments may be
      required for dance, particularly when ballet movements involve "turning out" or
      external rotation of the legs beyond that typically used in sports. This study
      evaluated the ability of the traditional single-leg squat to predict the leg
      alignment of dancers performing ballet movements with turnout. Three-dimensional
      kinematic data of dancers performing the single-leg squat and five ballet
      movements were recorded and analyzed. Reduction of the three-dimensional data
      into a one-dimensional variable incorporating the ankle, knee, and hip joint
      center positions provided the strongest predictive model between the single-leg
      squat and the ballet movements. The single-leg squat can predict leg alignment in
      dancers performing ballet movements, even in "turned out" postures. Clinicians
      should pay careful attention to observational positioning and rating criteria
      when assessing dancers performing the single-leg squat.

PMID- 27895519
TI  - Portal hypertension: an uncommon clinical manifestation of Takayasu arteritis in
      a 9-year-old child.
AB  - Takayasu arteritis (TA) is the third most common childhood vasculitis and its
      clinical manifestations depend on the arteries involved. We report a case of a 9
      year-old boy with multiple aneurysms in carotid and iliac arteries, subclavian
      and coronary arteries, and abdominal aorta. At the age of 7 years, he presented
      with recurrent fever and hepatosplenomegaly. An angio-computed tomography scan
      showed aneurysms in the left subclavian artery, abdominal aorta, and both
      proximal iliac arteries. He was diagnosed with TA and was treated with
      corticosteroids, aspirin, and enalapril. One year later, he was admitted to Dr
      Roberto Gilbert Children's Hospital because of intracranial hemorrhage.
      Angiography revealed enlargement of aneurysms enlargement and new aneurysms. He
      also developed portal hypertension. Treatment with intravenous corticosteroids,
      azathioprine, and monthly intravenous cyclophosphamide was begun. After 6 months
      of no improvement, infliximab was begun. The aim of this article was to report
      the concurrence of coronary involvement and portal vein hypertension in pediatric
      TA because there were scarce reports on this matter.

PMID- 27895520
TI  - Effectiveness of social work intervention with a systematic approach to improve
      general health in opioid addicts in addiction treatment centers.
AB  - PURPOSE: This study takes a systematic approach to investigate the effect of
      social work intervention aimed at increasing general health among opioid addicts
      in addiction treatment centers. PATIENTS AND METHODS: This is an experimental
      plan (pretest to posttest with a control group); the study sample included 60
      patients with drug dependencies undergoing treatment in addiction treatment
      centers. These patients were randomly assigned as case (30) and control (30)
      groups. The case group was subjected to intervention over ten sessions, whereas
      the control group received no intervention. Both groups then passed through a
      posttest, while a follow-up was conducted after 4 months. Data were obtained via
      a General Health Questionnaire. RESULTS: A covariance analysis test and
      independent and dependent t-test results indicated that a social work
      intervention adopting systematic approach was effective in increasing the general
      health of drug-addicted patients under treatment. CONCLUSION: Thus, the nature of
      the presence of social workers in addiction treatment centers has been effective
      and can have a significant influence by reducing anxiety and insomnia and somatic
      symptoms, improving patients' self-understanding and self-recognition, and
      enhancing social functioning.

PMID- 27895521
TI  - Impact of a medical university on laparoscopic surgery in a service-oriented
      public hospital in the Caribbean.
AB  - INTRODUCTION: The Caribbean lags behind global trends for volume and complexity
      of laparoscopic operations. In an attempt to promote laparoscopy at a single
      facility, a partnership was formed between the University of the West Indies
      (UWI) and the Port of Spain General Hospital in Trinidad and Tobago. This study
      seeks to document the effect of this partnership on laparoscopic practice.
      MATERIALS AND METHODS: In this partnership, the UWI took the bold step of
      volunteering to staff a surgical team if the Ministry of Health provided the
      necessary legislative changes. On August 1, 2013, a UWI team was introduced with
      a mandate to optimize teaching and promote laparoscopic surgery. The UWI team had
      a similar staff complement to the existing service-oriented teams. There was no
      immediate investment in equipment, hospital beds, ICU beds, or operating room
      space. Therefore, the new team was introduced with limited change in existing
      conditions, resources, and equipment. RESULTS: There were 252 laparoscopic
      operations performed over the study period. After introduction of the UWI team,
      there was an increase in the mean number of unselected laparoscopic operations
      (3.17 vs 10.83 cases per month; P<0.001; 95% confidence interval [95% CI] -8.5 to
      -6.84; standard error of the difference [SED] 0.408), the mean number of basic
      laparoscopic operations (3.17 vs 6.94 cases per month; P<0.0001; 95% CI -4.096 to
      -3.444; SED 0.165), the mean number of advanced laparoscopic operations (0 vs
      3.89; P<0.0001), the number of teams undertaking unselected laparoscopic
      operations (2 vs 5), and the number of teams independently performing advanced
      laparoscopic operations (0 vs 4). CONCLUSION: At this facility, we have
      demonstrated a significant increase in laparoscopic case volume and complexity
      when partnerships were formed between the UWI and this service-oriented hospital.
      Continued cross-fertilization and distribution of skill sets across the surgical
      community can reasonably be expected. We also identified maneuvers that can be
      used as a template to build laparoscopic services in other service-oriented
      hospitals in developing nations.

PMID- 27895522
TI  - Effects of tai chi chuan on anxiety and sleep quality in young adults: lessons
      from a randomized controlled feasibility study.
AB  - OBJECTIVE: To determine feasibility and estimate the effect of a 10-week tai chi
      chuan (TCC) intervention on anxiety and sleep quality in young adults.
      PARTICIPANTS: Seventy-five adults (18-40 years) from a predominately
      undergraduate midsized university. METHODS: This was an assessor blinded,
      randomized feasibility trial, and participants were randomized into one of three
      groups: 10 weeks of TCC meeting 2 times per week, 10 weeks of TCC with a DVD of
      the curriculum, and control group receiving a handout on anxiety management.
      Anxiety and sleep quality were assessed 4 times: baseline, 4 weeks, 10 weeks
      (immediate post-intervention), and 2 months post-intervention. Retention was
      defined as a participant attending the baseline assessment and at least one other
      assessment. Adherence to the intervention was set a priori as attendance at 80%
      of the TCC classes. RESULTS: Eighty-five percent of participants were retained
      during the intervention and 70% completed the 2 month follow-up assessments. To
      increase statistical power, the two TCC groups were combined in the analyses of
      anxiety and sleep quality measures. No significant changes in anxiety were found
      in the control group, while levels of anxiety decreased significantly over time
      in the two TCC groups. Sleep quality scores improved across time for all three
      groups, but adherent TCC participants reported greater improvement than control
      participants. CONCLUSION: TCC may be an effective nonpharmaceutical means of
      improving anxiety and poor sleep quality in young adults.

PMID- 27895523
TI  - Refinement of the Long-Term Conditions Questionnaire (LTCQ): patient and expert
      stakeholder opinion.
AB  - PURPOSE: It is a key UK government priority to assess and improve outcomes in
      people with long-term conditions (LTCs). We are developing a new patient-reported
      outcome measure, the Long-Term Conditions Questionnaire (LTCQ), for use among
      people with single or multiple LTCs. This study aimed to refine candidate LTCQ
      items that had previously been informed through literature reviews, interviews
      with professional stakeholders, and interviews with people with LTCs. MATERIALS
      AND METHODS: Cognitive interviews (n=32) with people living with LTCs and
      consultations with professional stakeholders (n=13) and public representatives
      (n=5) were conducted to assess the suitability of 23 candidate items. Items were
      tested for content and comprehensibility and underwent a translatability
      assessment. RESULTS: Four rounds of revisions took place, due to amendments to
      item structure, improvements to item clarity, item duplication, and
      recommendations for future translations. Twenty items were confirmed as relevant
      to living with LTCs and understandable to patients and professionals. CONCLUSION:
      This study supports the content validity of the LTCQ items among people with LTCs
      and professional stakeholders. The final items are suitable to enter the next
      stage of psychometric refinement.

PMID- 27895525
TI  - A survey of the spider family Nesticidae (Arachnida, Araneae) in Asia and
      Madagascar, with the description of forty-three new species.
AB  - Forty-three new species of Nesticidae are described from China, Indonesia,
      Philippines, Singapore, Thailand, Vietnam and Madagascar, and two new junior
      synonyms are suggested. A new genus, Speleoticusgen. n., is described with
      Nesticus navicellatus Liu & Li, 2013 as the type species, and four species are
      transferfed from Nesticus, i.e., Speleoticus globosus (Liu & Li, 2013), comb. n.,
      Speleoticus libo (Chen & Zhu, 2005), comb. n., Speleoticus navicellatus (Liu &
      Li, 2015), comb. n. and Speleoticus uenoi (Yaginuma, 1972), comb. n. The new
      species described in this paper belong to four genera and are: Hamus cornutussp.
      n. (??), Hamus kangdingensissp. n. (?), Hamus luzonsp. n. (?), Hamus
      mangunensissp. n. (?), Nescina kohisp. n. (??), Nesticella baiseensissp. n. (??),
      Nesticella baobabsp. n. (?), Nesticella caecasp. n. (??), Nesticella chongqingsp.
      n. (?), Nesticella dazhuangensissp. n. (??), Nesticella fuliangensissp. n. (??),
      Nesticella gazuidasp. n. (?), Nesticella gongshanensissp. n. (?), Nesticella
      griswoldisp. n. (??), Nesticella hongheensissp. n. (??), Nesticella
      huomachongensissp. n. (??), Nesticella jingposp. n. (?), Nesticella
      kaohsiungensissp. n. (??), Nesticella lisusp. n. (??), Nesticella liuzhaiensissp.
      n. (?), Nesticella nandanensissp. n. (??), Nesticella phamisp. n. (??),
      Nesticella potalasp. n. (?), Nesticella qiaoqiensissp. n. (?), Nesticella
      qiongensissp. n. (??), Nesticella robustasp. n. (??), Nesticella rongtangensissp.
      n. (?), Nesticella sanchaheensissp. n. (??), Nesticella sulawesisp. n. (?),
      Nesticella sumatranasp. n. (?), Nesticella tibetanasp. n. (??), Nesticella
      vanlangsp. n. (?), Nesticella wanzaiensissp. n. (??), Nesticella xiongmaosp. n.
      (??), Nesticella xixiasp. n. (??), Nesticella yanbeiensissp. n. (??), Nesticella
      yaosp. n. (?), Nesticella zhiyuanisp. n. (??), Pseudonesticus dafangensissp. n.
      (??), Pseudonesticus miaosp. n. (??), Pseudonesticus spinosussp. n. (??),
      Pseudonesticus wumengensissp. n. (?), Pseudonesticus ziyunensissp. n. (??).
      Nesticella inthanoni (Lehtinen & Saaristo, 1980), syn. n. is synonymised with
      Nesticella mollicula (Thorell, 1898); Nesticella taiwan Tso & Yoshida, 2000, syn.
      n. is synonymised with Nesticella odonta (Chen, 1984). The female of Nesticella
      connectens Wunderlich, 1995, so far unknown, is described and recorded from
      Thailand. Nesticidae are reported from Madagascar for the first time. Nesticella
      nepalensis (Hubert, 1973) is recorded for the first time from China. Types of
      Nesticella odonta (Chen, 1984), Nesticella songi Chen & Zhu, 2004 and Nesticella
      yui Wunderlich & Song, 1995 are re-examined and photographed. The entire genus
      Nesticella is reviewed, and four species groups are recognised. DNA barcodes of
      the new species are obtained to confirm their correct identifications.

PMID- 27895524
TI  - Characteristics of social drinkers with and without a hangover after heavy
      alcohol consumption.
AB  - BACKGROUND: A number of social drinkers claim that they do not experience next
      day hangovers despite consuming large quantities of alcohol. The aim of this
      study was to investigate the characteristics of drinkers who claim to be hangover
      immune and compare them with drinkers who do report having hangovers. METHODS: A
      total of 36 social drinkers participated in a naturalistic study consisting of a
      hangover day (alcohol consumed) and a control day (no alcohol consumed). Data
      were collected on alcohol consumption, demographics, sleep, next-day adverse
      effects, and mood. Data from drinkers with a hangover (N=18) were compared with
      data from drinkers who claim to be hangover immune (N=18). RESULTS: Drinkers with
      a hangover reported drowsiness-related symptoms, symptoms related to reduced
      cognitive functioning, and classic hangover symptoms such as headache, nausea,
      dizziness, weakness, and stomach pain. Corresponding mood changes comprised
      increased feelings of depression, anger-hostility, fatigue, and reduced vigor
      activity. In contrast, hangover-immune drinkers reported relatively few hangover
      symptoms, with only mild corresponding severity scores. The reported symptoms
      were limited to drowsiness-related symptoms such as sleepiness and being tired.
      The classic hangover symptoms were usually not reported by these drinkers.
      CONCLUSION: In contrast to drinkers with a hangover, for those who claim to be
      hangover immune, next-day adverse effects of alcohol consumption are limited to a
      mild increase in drowsiness-related symptoms.

PMID- 27895526
TI  - Development of a simple and specific direct competitive ELISA for the
      determination of artesunate using an anti-artesunate polyclonal antiserum.
AB  - BACKGROUND: Since artesunate (ART) became a vital component of artemisinin (ARM)
      based combination therapies for the treatment for malaria, counterfeit ART drugs
      have spread in regions of Southeast Asia and Africa. The consumption of
      counterfeit ART drugs has resulted in the death of many patients. Thus,
      evaluating the quality of ART drugs is needed. There are several methods for
      quantitating the ART content in tablets, the most common being a high-performance
      liquid chromatography. However, that method is hampered by the need for expensive
      equipment and a rather time-consuming process of extraction. By contrast, enzyme
      linked immunosorbent assays (ELISAs) are faster and much less expensive, and they
      require less sample preparation than the above method. The objective of the
      present study was to establish a simple and specific direct competitive ELISA for
      the determination of ART concentrations using an anti-ART polyclonal antibody
      (pAb). RESULTS: Anti-ART pAb was raised in mice, and ART-horseradish peroxidase
      (HRP) conjugate was produced. A direct competitive ELISA was performed by
      simultaneously incubating ART and the ART-HRP conjugate with the anti-ART pAb
      over a second antibody. Subsequently, the enzyme activity of the remaining ART
      HRP conjugate was measured. The intra- and inter-assay coefficients of variation
      of the ELISA were less than 10 % in the range of 0.3 to 30 ng/ml with a detection
      limit of 0.1 ng/ml. The cross-reactivities of the anti-ART pAb with ARM and
      dihydroartemisinin were 0.12 and 0.04 %, respectively, and those with other
      antimalarial drugs were negligible. Furthermore, the recovery of 10 or 50 ng/ml
      ART added to the drug tablet solutions containing an expected amount of 10 ng/ml
      was estimated by the ELISA. The recovery of the ART amount ranged between 98 and
      106 %, with coefficient variations of less than 7.0 %. CONCLUSIONS: The present
      ELISA is a simple and specific method for the determination of ART
      concentrations. Thus, this ELISA can be used to identify ART counterfeits and
      substandard drugs and to quantify the ART drugs.

PMID- 27895527
TI  - Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic
      Sarcoma.
AB  - Background. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous antiangiogenic hormone
      with anticancer activity. In a phase I study of Ang-(1-7), two of three patients
      with metastatic sarcoma experienced disease stabilization. This phase II study
      examined clinical and biomarker outcomes for patients with metastatic sarcoma.
      Methods. Ang-(1-7) was administered by subcutaneous injection at a dose of 20 mg
      daily. If excessive toxicities occurred in the first cohort, a dose deescalation
      cohort was allowed. Blood samples were obtained to measure changes in biomarkers.
      Results. Treatment was well-tolerated and the dose deescalation cohort was not
      required. Plasma PlGF concentrations following treatment were not statistically
      significantly changed. A significant increase in plasma Ang-(1-7) was observed at
      4 hours after injection. The median progression-free survival was 2.7 months (95%
      CI; 1.4 to 4.1 months), and the median overall survival was 10.2 months (95% CI;
      5.3 to 18.3 months). Two patients with vascular sarcomas demonstrated prolonged
      disease stabilization of 10 months (hemangiopericytoma) and 19 months
      (epithelioid hemangioendothelioma). Conclusions. Ang-(1-7) at a dose of 20 mg
      daily was well-tolerated. This prospective phase II study failed to confirm the
      PlGF biomarker effect identified in the prior phase I study. Prolonged disease
      stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may
      warrant further investigation.

PMID- 27895528
TI  - Nurses' perceptions of a pressure ulcer prevention care bundle: a qualitative
      descriptive study.
AB  - BACKGROUND: Pressure ulcer prevention is a critical patient safety indicator for
      acute care hospitals. An innovative pressure ulcer prevention care bundle
      targeting patient participation in their care was recently tested in a cluster
      randomised trial in eight Australian hospitals. Understanding nurses'
      perspectives of such an intervention is imperative when interpreting results and
      translating evidence into practice. As part of a process evaluation for the main
      trial, this study assessed nurses' perceptions of the usefulness and impact of a
      pressure ulcer prevention care bundle intervention on clinical practice. METHODS:
      This qualitative descriptive study involved semi-structured interviews with
      nursing staff at four Australian hospitals that were intervention sites for a
      cluster randomised trial testing a pressure ulcer prevention care bundle. Four to
      five participants were purposively sampled at each site. A trained interviewer
      used a semi-structured interview guide to question participants about their
      perceptions of the care bundle. Interviews were digitally recorded, transcribed
      and analysed using thematic analysis. RESULTS: Eighteen nurses from four
      hospitals participated in the study. Nurses' perceptions of the intervention are
      described in five themes: 1) Awareness of the pressure ulcer prevention care
      bundle and its similarity to current practice; 2) Improving awareness,
      communication and participation with the pressure ulcer prevention care bundle;
      3) Appreciating the positive aspects of patient participation in care; 4)
      Perceived barriers to engaging patients in the pressure ulcer prevention care
      bundle; and 5) Partnering with nursing staff to facilitate pressure ulcer
      prevention care bundle implementation. CONCLUSIONS: Overall, nurses found the
      care bundle feasible and acceptable. They identified a number of benefits from
      the bundle, including improved communication, awareness and participation in
      pressure ulcer prevention care among patients and staff. However, nurses thought
      the care bundle was not appropriate or effective for all patients, such as those
      who were cognitively impaired. Perceived enablers to implementation of the bundle
      included facilitation through effective communication and dissemination of
      evidence about the care bundle; strong leadership and ability to influence staff
      behaviour; and simplicity of the care bundle.

PMID- 27895529
TI  - Assessing nursing staff's competences in mobility support in nursing-home care:
      development and psychometric testing of the Kinaesthetics Competence (KC)
      observation instrument.
AB  - BACKGROUND: Between 75 and 89% of residents living in long-term care facilities
      have limited mobility. Nurses as well as other licensed and unlicensed personnel
      directly involved in resident care are in a key position to promote and maintain
      the mobility of care-dependent persons. This requires a certain level of
      competence. Kinaesthetics is a training concept used to increase nursing staff's
      interaction and movement support skills for assisting care-dependent persons in
      their daily activities. This study aims to develop and test an observation
      instrument for assessing nursing staff's competences in kinaesthetics. METHODS:
      The Kinaesthetics Competence (KC) observation instrument was developed between
      January and June 2015 based on a literature review, a concept analysis and expert
      meetings (18). The pilot instrument was evaluated with two expert panels (n = 5,
      n = 4) regarding content validity, usability and inter-rater agreement. Content
      validity was assessed by determining the content validity index (CVI). The final
      instrument was tested in a cross-sectional study in three nursing homes in the
      German-speaking part of Switzerland between July 2015 and February 2016. In this
      study nursing staff (n = 48) was filmed during mobilization situations. Based on
      this video data two observers independently assessed nursing staff's competences
      in kinaesthetics with the KC observation instrument. Inter-rater reliability and
      inter-rater agreement was evaluated using the intra-class correlation coefficient
      (ICC) and percentage of agreement. Construct validity was assessed by a
      discriminating power analysis. Internal consistency was evaluated using
      Cronbach's alpha coefficient and item analysis. RESULTS: The final version of the
      KC observation instrument comprised of four domains (interaction, movement
      support of the person, nurses' movement, environment) and 12 items. The final
      instrument showed an excellent content validity index of 1.0. Video sequences
      from 40 persons were analysed. Inter-rater reliability for the whole scale was
      good (ICC 0.73) and the percentage of inter-rater agreement was 53.6% on average.
      Cronbach's alpha coefficient for the whole instrument was 0.97 and item-total
      correlations ranged from 0.76 to 0.90. The construct validity of the instrument
      was supported by a significant discrimination of the instrument between nursing
      staff with no or basic and with advanced kinaesthetics training for the total
      score and 3 of 4 subscales. CONCLUSIONS: The KC observation instrument showed
      good preliminary psychometric properties and can be used to assess nursing
      staff's competences in mobility care based on the principles of kinaesthetics.

PMID- 27895530
TI  - Alpha-synuclein contributes to malignant progression of human meningioma via the
      Akt/mTOR pathway.
AB  - BACKGROUND: The aim of this study is to explore the expression of alpha-synuclein
      (alpha-synuclein) in benign, atypical, and anaplastic meningiomas and determine
      its role in the malignant progression of meningiomas. METHODS: Expression of
      alpha-synuclein was measured in 44 meningioma samples by real-time PCR analysis.
      The effects of overexpression or knockdown of alpha-synuclein on meningioma cell
      growth, invasiveness, and tumorigenicity were determined. RESULTS: Atypical and
      anaplastic meningiomas displayed significantly greater levels of alpha-synuclein
      mRNA, relative to benign tumors. Depletion of alpha-synuclein decreased cell
      proliferation and colony formation and promoted apoptosis in IOMM-Lee meningioma
      cells, whereas overexpression of alpha-synuclein facilitated cell proliferation
      and colony formation in CH-157MN meningioma cells. Silencing of alpha-synuclein
      attenuated IOMM-Lee cell migration and invasion. In contrast, ectopic expression
      of alpha-synuclein increased the invasiveness of CH-157MN cells. In vivo studies
      further demonstrated that downregulation of alpha-synuclein significantly
      retarded meningioma growth in nude mice. At the molecular level, the
      phosphorylation levels of Akt, mTOR, p70S6K and 4EBP were significantly decreased
      in alpha-synuclein-depleted IOMM-Lee cells. CONCLUSIONS: In conclusion, alpha
      synuclein upregulation contributes to aggressive phenotypes of meningiomas via
      the Akt/mTOR pathway and thus represents a potential therapeutic target for
      malignant meningiomas.

PMID- 27895532
TI  - CD163 macrophage and erythrocyte contents in aspirated deep vein thrombus are
      associated with the time after onset: a pilot study.
AB  - BACKGROUND: Thrombolytic therapy is effective in selected patients with deep vein
      thrombosis (DVT). Therefore, identification of a marker that reflects the age of
      thrombus is of particular concern. This pilot study aimed to identify a marker
      that reflects the time after onset in human aspirated DVT. METHODS: We
      histologically and immunohistochemically analyzed 16 aspirated thrombi. The times
      from onset to aspiration ranged from 5 to 60 days (median of 13 days). Paraffin
      sections were stained with hematoxylin and eosin and antibodies for fibrin,
      glycophorin A, integrin alpha2bbeta3, macrophage markers (CD68, CD163, and
      CD206), CD34, and smooth muscle actin (SMA). RESULTS: All thrombi were
      immunopositive for glycophorin A, fibrin, integrin alpha2bbeta3, CD68, CD163, and
      CD206, and contained granulocytes. Almost all of the thrombi had small foci of
      CD34- or SMA-immunopositive areas. CD68- and CD163-immunopositive cell numbers
      were positively correlated with the time after onset, while the glycophorin A
      immunopositive area was negatively correlated with the time after onset. In
      double immunohistochemistry, CD163-positive cells existed predominantly among the
      CD68-immunopositive macrophage population. CD163-positive macrophages were
      closely localized with glycophorin A, CD34, or SMA-positive cell-rich areas.
      CONCLUSIONS: These findings indicate that CD163 macrophage and erythrocyte
      contents could be markers for evaluation of the age of thrombus in DVT.
      Additionally, CD163 macrophages might play a role in organization of the process
      of venous thrombus.

PMID- 27895531
TI  - Follicular fluid biomarkers for human in vitro fertilization outcome: Proof of
      principle.
AB  - BACKGROUND: Human follicular fluid (FF) is a unique biological fluid in which the
      oocyte develops in vivo, and presents an optimal source for non-invasive
      biochemical predictors. Oocyte quality directly influences the embryo development
      and hence, may be used as a predictor of embryo quality. Peptide profiling of FF
      and its potential use as a biomarker for oocyte quality has never been reported.
      METHODS: This study screened FF for peptide biomarkers that predict the outcome
      of in vitro fertilization (IVF). Potential biomarkers were discovered by
      investigating 2 training datasets, consisting both of 17 samples and validating
      on an independent experiment containing 32 samples. Peptide profiles were
      acquired by nano-scale liquid chromatography coupled to tandem mass spectrometry
      (nano LC-MS/MS). RESULTS: From the training datasets 53 peptides were found as
      potential biomarker candidates, predicting the fertilization outcome of 24 out of
      the 32 validation samples blindly (81.3% sensitivity, 68.8% specificity, AUC =
      0.86). Seven potential biomarker peptides were identified. They were derived
      from: insulin-like growth factor binding protein-5, alpha-2-antiplasmin,
      complement component 3, inter-alpha-trypsin inhibitor heavy chain H1, serum
      albumin, protein diaphanous homolog 1 and plastin-3. CONCLUSIONS: The MS-based
      comprehensive peptidomic approach carried out in this study, established a novel
      panel of potential biomarkers that present a promising predictive accuracy rate
      in fertilization outcome, and indicates FF as an interesting biomarker resource
      to improve IVF clinic routine.

PMID- 27895533
TI  - Type 2 diabetes detection and management among insured adults.
AB  - BACKGROUND: The Centers for Disease Control and Prevention estimates that 28.9
      million adults had diabetes in 2012 in the US, though many patients are
      undiagnosed or not managing their condition. This study provides US national and
      state estimates of insured adults with type 2 diabetes who are diagnosed,
      receiving exams and medication, managing glycemic levels, with diabetes
      complications, and their health expenditures. Such information can be used for
      benchmarking and to identify gaps in diabetes detection and management. METHODS:
      The study combines analysis of survey data with medical claims analysis for the
      commercially insured, Medicare, and Medicaid populations to estimate the number
      of adults with diagnosed type 2 diabetes and undiagnosed diabetes by insurance
      type, age, and sex. Medical claims analysis used the 2012 de-identified Normative
      Health Information database covering a nationally representative commercially
      insured population, the 2011 Medicare 5% Sample, and the 2008 Medicaid Mini-Max.
      RESULTS: Among insured adults in 2012, approximately 16.9 million had diagnosed
      type 2 diabetes, 1.45 million had diagnosed type 1 diabetes, and 6.9 million had
      undiagnosed diabetes. Of those with diagnosed type 2, approximately 13.0 million
      (77%) received diabetes medication-ranging from 70% in New Jersey to 82% in Utah.
      Suboptimal percentages had claims indicating recommended exams were performed. Of
      those receiving diabetes medication, 43% (5.6 million) had medical claims
      indicating poorly controlled diabetes-ranging from 29% with poor control in
      Minnesota and Iowa to 53% in Texas. Poor control was correlated with higher
      prevalence of neurological complications (+14%), renal complications (+14%), and
      peripheral vascular disease (+11%). Patients with poor control averaged $4,860
      higher average annual health care expenditures-ranging from $6,680 for
      commercially insured patients to $4,360 for Medicaid and $3,430 for Medicare
      patients. CONCLUSIONS: This study highlights the large number of insured adults
      with undiagnosed type 2 diabetes by insurance type and state. Furthermore, this
      study sheds light on other gaps in diabetes care quality among patients with
      diagnosed diabetes and corresponding poorly controlled diabetes. These findings
      underscore the need for improvements in data collection and diabetes screening
      and management, along with policies that support these improvements.

PMID- 27895535
TI  - William C. Pederson, MD.

PMID- 27895536
TI  - Pediatric Plastic Surgical Procedures.

PMID- 27895534
TI  - An Automated Perifusion System for Modifying Cell Culture Conditions over Time.
AB  - BACKGROUND: Cells are continuously exposed to changes in their environment.
      Endocrine systems, in particular, communicate by rhythms and feedback loops. In
      this study, we developed an automated system to produce such conditions for
      cultured cells in a precisely timed manner. We utilized a programmable pair of
      syringe pumps for inflow and a peristaltic pump for outflow to create rhythmic
      pulses at 5-min intervals in solutions that mimic the endogenous patterns of
      insulin produced by pancreatic islets as a test case. RESULTS: This perifusion
      system was first tested by measuring trypan blue absorbance, which was
      intermittently added and washed out at 3:3 and 2:3 min (in:out). Absorbance
      corresponded with patterns of trypan blue delivery. We then created patterns of
      forced oscillations in islets by intermittently switching between solutions
      containing 28 millimolar (mM) glucose (producing high levels of intracellular
      calcium ([Ca2+]i) and insulin secretion) and 28 mM glucose + calcium-channel
      blocker nifedipine (producing low levels of [Ca2+]i and insulin secretion).
      Forced perifusion effects were monitored by fura-2 AM fluorescence measurements
      of [Ca2+]i. Islets showed uniform oscillations in [Ca2+]i at time intervals
      consistent with the perifusion pattern, mimicking endogenous pulsatility.
      CONCLUSIONS: This study highlights a valuable method to modify the environment of
      the cell culture over a period of hours to days.

PMID- 27895537
TI  - Tissue Expansion in Children.
AB  - Tissue expansion is a well-established surgical method that has been creatively
      applied to the management of many congenital and acquired pediatric conditions,
      including the removal of giant congenital melanocytic nevi and the separation of
      conjoined twins. Careful preoperative planning and patient follow-up are required
      to achieve the proper results and minimize complications. Special considerations
      for pediatric patients are present during each step of the process, from patient
      selection to postoperative care. The complication rate in tissue expansion
      remains high, though measures can be taken to reduce and effectively manage these
      complications.

PMID- 27895539
TI  - Practical Considerations in Pediatric Surgery.
AB  - The care of pediatric patients requires special considerations that are often not
      addressed in the literature. Relatively straightforward tasks such as clinical
      evaluation, antibiotic use, splinting, wound closure, and care of simple burns
      become complicated in the pediatric population for several reasons. The authors
      seek to demystify some of these topics using the senior author's years of
      clinical experience treating pediatric patients by giving practical advice and
      general considerations when treating children.

PMID- 27895538
TI  - Syndactyly Release.
AB  - Syndactyly is one of the most common congenital hand anomalies treated by
      pediatric plastic surgeons. Established principles of syndactyly separation
      dictate the timing and order of syndactyly release, with the goals of surgery
      being the creation of an anatomically normal webspace, tension-free closure of
      soft tissue, and return of function to the fingers. Numerous surgical methods
      have been described, many of which involve the use of local flaps to reconstruct
      the commissure and full-thickness skin grafts for coverage of raw areas.
      Recently, reconstructive techniques without the use of skin grafts have been
      devised, which work well for certain indications. Special considerations are
      described for complete, complex, and syndromic syndactylies. Outcomes for simple
      syndactyly release are typically good when surgical principles are followed,
      whereas complex syndactyly release tends to have less-favorable outcomes and more
      complications.

PMID- 27895540
TI  - Midline Craniofacial Masses in Children.
AB  - Nasal dermoids, encephaloceles, and gliomas are rare congenital lesions that
      result from improper embryologic development. The differentiation between them
      and a firm understanding of their pathology is necessary to avoid unnecessary
      complications. In view of their potential intracranial connection, prompt
      diagnosis and treatment are paramount. The authors review the embryology,
      diagnoses, radiologic work-up, surgical management, and complications of these
      midline craniofacial masses in children.

PMID- 27895541
TI  - The Duplicated Thumb: A Review.
AB  - Preaxial polydactyly is a common, often sporadic, congenital anomaly that must be
      addressed surgically early in life. Ideally, the surgeon seeks to accomplish
      three goals: construction of a thumb that is adequate in size, preservation of
      pinch function, and reconstruction of all components in one procedure. Although
      each case is unique, several classification systems attempt to describe the
      various types. In this article, the authors discuss the various classification
      systems, procedures, and outcomes after surgery for pediatric thumb duplication.

PMID- 27895542
TI  - Effect of tart cherry juice on recovery and next day performance in well-trained
      Water Polo players.
AB  - BACKGROUND: Tart Montmorency cherries contain high concentrations of
      phytochemicals and anthocyanins, which have recently been linked to improved
      athletic recovery and subsequent performance. To date however, previous work
      reporting promising results has focused on land-based endurance sports, with any
      potential benefits to team sports remaining unknown. As such, this investigation
      set-out to examine the effect of supplemental tart cherry juice (CJ) on recovery
      and next day athletic performance in highly-trained water-based team sport
      athletes over seven days. METHODS: In a randomised, double-blind, repeated
      measures, crossover design, nine male Water Polo athletes were supplemented with
      CJ or a placebo equivalent (PLA) for six consecutive days. Prior to, and at the
      completion of the supplementation period, water-based performance testing was
      conducted. On day 6, participants also undertook a fatiguing simulated team game
      activity. Venous blood samples were collected (Pre-exercise: day 1, 6 and 7; Post
      exercise: day 6) to investigate markers of inflammation [Interleukin-6 (IL-6); C
      reactive protein (CRP)] and oxidative stress [Uric Acid (UA); F2-Isoprostane (F2
      IsoP)]. A daily diary was also completed (total quality of recovery, delayed
      onset muscle soreness) as a measure of perceptual recovery. RESULTS: In both
      conditions, day 6 post-exercise IL-6 was significantly higher than pre-exercise
      and day 7 (p < 0.05); CRP was greater on day 7 as compared to day 6 pre- and post
      exercise (p < 0.05); F2-IsoP was significantly lower on day 7 as compared to day
      1 and day 6 (p < 0.05); UA remained unchanged (p > 0.05). No differences were
      found for any performance or recovery measures. CONCLUSIONS: The lack of
      difference observed in the blood markers between groups may reflect the
      intermittent, non-weight bearing demands of Water Polo, with such activity
      possibly unable to create a substantial inflammatory response or oxidative stress
      (over 7 days) to impede performance; thereby negating any potential beneficial
      effects associated with CJ supplementation. TRIAL REGISTRATION: This trial was
      registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR).
      Registration number: ACTRN12616001080415. Date registered: 11/08/2016,
      retrospectively registered.

PMID- 27895543
TI  - Proteome analysis of excretory-secretory proteins of Entamoeba histolytica
      HM1:IMSS via LC-ESI-MS/MS and LC-MALDI-TOF/TOF.
AB  - BACKGROUND: Excretory-secretory (ES) proteins of E. histolytica are thought to
      play important roles in the host invasion, metabolism, and defence. Elucidation
      of the types and functions of E. histolytica ES proteins can further our
      understanding of the disease pathogenesis. Thus, the aim of this study is to use
      proteomics approach to better understand the complex ES proteins of the protozoa.
      METHODS: E. histolytica ES proteins were prepared by culturing the trophozoites
      in protein-free medium. The ES proteins were identified using two mass
      spectrometry tools, namely, LC-ESI-MS/MS and LC-MALDI-TOF/TOF. The identified
      proteins were then classified according to their biological processes, molecular
      functions, and cellular components using the Panther classification system
      (PantherDB). RESULTS: A complementary list of 219 proteins was identified; this
      comprised 201 proteins detected by LC-ESI-MS/MS and 107 proteins by LC-MALDI
      TOF/TOF. Of the 219 proteins, 89 were identified by both mass-spectrometry
      systems, while 112 and 18 proteins were detected exclusively by LC-ESI-MS/MS and
      LC-MALDI-TOF/TOF respectively. Biological protein functional analysis using
      PantherDB showed that 27% of the proteins were involved in metabolic processes.
      Using molecular functional and cellular component analyses, 35% of the proteins
      were found to be involved in catalytic activity, and 21% were associated with the
      cell parts. CONCLUSION: This study showed that complementary use of LC-ESI-MS/MS
      and LC-MALDI-TOF/TOF has improved the identification of ES proteins. The results
      have increased our understanding of the types of proteins excreted/secreted by
      the amoeba and provided further evidence of the involvement of ES proteins in
      intestinal colonisation and evasion of the host immune system, as well as in
      encystation and excystation of the parasite.

PMID- 27895544
TI  - Mesoporous silica chip: enabled peptide profiling as an effective platform for
      controlling bio-sample quality and optimizing handling procedure.
AB  - BACKGROUND: High quality clinical samples are critical for meaningful
      interpretation of data obtained in both basic and translational medicine. More
      specifically, optimized pre-analysis handling to bio-sample is crucial for
      avoiding biased analysis in a clinical setting. A universally applicable method
      for the evaluation of sample quality and pre-analysis handling is therefore in
      great demand. METHODS: The fingerprint pattern of low molecular weight (LMW)
      peptides in sera is directly associated with sample quality and handling process.
      Previous studies for enrichment/isolation of LMW peptides have shown that LMW
      peptides can be enriched by silica meso-porous material in a sensitive and high
      throughput manner. Here, a peptide profile approach utilizing mesoporous silica
      chip-based sample preparation combined with MALDI MS analysis was used as a new
      platform for evaluation of bio-sample quality. Rat sera were selected as model
      sample and analyzed according to their LMW peptide fingerprint spectra. RESULTS:
      This novel method can complete the entire sample preparation procedure in a short
      period of time (<40 min), requires minimum amounts of sample (<10 uL), is of high
      sensitivity (LOD 10 ng/mL) as well as high reproducibility (CV% < 15%). According
      to the acquired LMW peptide spectra, we were able to distinguish the serum
      samples processed under different conditions (including different storage
      temperature, time, and freezing/thaw cycles) with the help of bioinformatics
      tools (principle composition analysis and significant difference analysis), and
      identify the samples that had significantly changed due to the inappropriate
      processing. Based on the percentage of significantly changed peaks in LMW peptide
      mass spectrum after handling, a judgment standard was established that can be
      used to evaluate the status of preservation of a biological sample. In addition,
      our principle study established recommendations for storage time, storage
      temperature and freeze/thaw conditions. CONCLUSION: Our novel method for analysis
      of bio-samples allows for effective identification of variations in composition
      within samples, and provides a cost-effective tool for simple sample manipulation
      in a clinical setting.

PMID- 27895545
TI  - Studying the Complex Relationships Between Physical Activity and Infertility.
AB  - This article provides commentary on the accompanying review, "Modifiable Risk
      Factors and Infertility: What are the Connections?" by Rossi and colleagues. This
      commentary focuses specifically on the association between physical activity or
      exercise and infertility, given the equivocal evidence summarized in the Rossi et
      al. review paper. Several methodologic issues related to physical activity and
      infertility are discussed, including defining the components of physical activity
      that research studies assess in research studies (e.g., type, intensity,
      frequency, duration); considering the optimal way to measure physical activity;
      and investigating important effect modifiers, including age and body mass index.
      Researchers should also consider sedentary behavior as another potentially
      important, unexplored, modifiable behavior that may be associated with
      infertility. Given that unexplained infertility remains of widespread global
      concern, identifying modifiable risk factors and how much influence they have on
      infertility remains an important area for research.

PMID- 27895546
TI  - A gaping gap (smokeless tobacco control in Pakistan).
AB  - Oral cancer is second most common cancer in Pakistan and one of the major
      contributing factors to its high incidence is smokeless tobacco (SLT) use. 5.3%
      of Pakistan's youth are current SLT users. The World Health Organization requires
      the signatories of its "Framework Convention on Tobacco Control" to officially
      ban the sale of tobacco products to minors. We reviewed the Government of
      Pakistan's tobacco control, and related supporting policies, to assess how these
      address the issue of sale of SLT products to minors and found evident gaps in
      this regard. Legislations need to be in place to ban the sale of SLT products to
      minors and avoid an SLT epidemic in the future.

PMID- 27895547
TI  - Editorial: Recent Advances and Challenges on Big Data Analysis in Neuroimaging.

PMID- 27895549
TI  - The Repeatable Battery for the Assessment of Neuropsychological Status for
      Hearing Impaired Individuals (RBANS-H) before and after Cochlear Implantation: A
      Protocol for a Prospective, Longitudinal Cohort Study.
AB  - Background: Currently, an independent relationship between hearing loss and
      cognitive decline in older adults is suggested by large prospective studies. In
      general, cochlear implants improve hearing and the quality of life in severely to
      profoundly hearing impaired older persons. However, little is known about the
      effects of cochlear implantation on the cognitive evolution in this population.
      Aim of the study: The primary goal of this prospective, longitudinal cohort study
      is to explore the cognitive profile of severely to profoundly postlingually
      hearing impaired subjects before and after cochlear implantation. In addition,
      the current study aims to investigate the relationship between the cognitive
      function, audiometric performances, quality of life, and self-reliance in these
      patients. Methods: Twenty-five patients aged 55 or older, scheduled for cochlear
      implantation, will be enrolled in the study. They will be examined prior to
      implantation, at 6 and 12 months after implantation and annually thereafter. The
      test battery consists of (1) a cognitive examination, using the Repeatable
      Battery for the Assessment of Neuropsychological Status adapted for Hearing
      impaired persons (RBANS-H), (2) an audiological examination, including unaided
      and aided pure tone audiometry, speech audiometry in quiet and speech audiometry
      in noise, (3) the administration of four questionnaires evaluating quality of
      life and subjective hearing benefit and (4) a semi-structured interview about the
      self-reliance of the participant. Discussion: Up until now only one study has
      been conducted on this topic, focusing on the short-term effects of cochlear
      implantation on cognition in older adults. The present study is the first study
      to apply a comprehensive neuropsychological assessment adapted for severely to
      profoundly hearing impaired subjects in order to investigate the cognitive
      capabilities before and after cochlear implantation. Trial registration: The
      present protocol is retrospectively registered at Clinical Trials
      (ClinicalTrials.gov) on June 9th, 2016. The first participant was enrolled on
      June 22nd, 2015. The protocol identifier is NCT02794350.

PMID- 27895548
TI  - A Novel Microfluidic Cell Co-culture Platform for the Study of the Molecular
      Mechanisms of Parkinson's Disease and Other Synucleinopathies.
AB  - Although, the precise molecular mechanisms underlying Parkinson's disease (PD)
      are still elusive, it is now known that spreading of alpha-synuclein (aSyn)
      pathology and neuroinflammation are important players in disease progression.
      Here, we developed a novel microfluidic cell-culture platform for studying the
      communication between two different cell populations, a process of critical
      importance not only in PD but also in many biological processes. The integration
      of micro-valves in the device enabled us to control fluid routing, cellular
      microenvironments, and to simulate paracrine signaling. As proof of concept, two
      sets of experiments were designed to show how this platform can be used to
      investigate specific molecular mechanisms associated with PD. In one experiment,
      naive H4 neuroglioma cells were co-cultured with cells expressing aSyn tagged
      with GFP (aSyn-GFP), to study the release and spreading of the protein. In our
      experimental set up, we induced the release of the contents of aSyn-GFP producing
      cells to the medium and monitored the protein's diffusion. In another experiment,
      H4 cells were co-cultured with N9 microglial cells to assess the interplay
      between two cell lines in response to environmental stimuli. Here, we observed an
      increase in the levels of reactive oxygen species in H4 cells cultured in the
      presence of activated N9 cells, confirming the cross talk between different cell
      populations. In summary, the platform developed in this study affords novel
      opportunities for the study of the molecular mechanisms involved in PD and other
      neurodegenerative diseases.

PMID- 27895550
TI  - Closed-Loop Task Difficulty Adaptation during Virtual Reality Reach-to-Grasp
      Training Assisted with an Exoskeleton for Stroke Rehabilitation.
AB  - Stroke patients with severe motor deficits of the upper extremity may practice
      rehabilitation exercises with the assistance of a multi-joint exoskeleton.
      Although this technology enables intensive task-oriented training, it may also
      lead to slacking when the assistance is too supportive. Preserving the engagement
      of the patients while providing "assistance-as-needed" during the exercises,
      therefore remains an ongoing challenge. We applied a commercially available seven
      degree-of-freedom arm exoskeleton to provide passive gravity compensation during
      task-oriented training in a virtual environment. During this 4-week pilot study,
      five severely affected chronic stroke patients performed reach-to-grasp exercises
      resembling activities of daily living. The subjects received virtual reality
      feedback from their three-dimensional movements. The level of difficulty for the
      exercise was adjusted by a performance-dependent real-time adaptation algorithm.
      The goal of this algorithm was the automated improvement of the range of motion.
      In the course of 20 training and feedback sessions, this unsupervised adaptive
      training concept led to a progressive increase of the virtual training space (p <
      0.001) in accordance with the subjects' abilities. This learning curve was
      paralleled by a concurrent improvement of real world kinematic parameters, i.e.,
      range of motion (p = 0.008), accuracy of movement (p = 0.01), and movement
      velocity (p < 0.001). Notably, these kinematic gains were paralleled by motor
      improvements such as increased elbow movement (p = 0.001), grip force (p <
      0.001), and upper extremity Fugl-Meyer-Assessment score from 14.3 +/- 5 to 16.9
      +/- 6.1 (p = 0.026). Combining gravity-compensating assistance with adaptive
      closed-loop feedback in virtual reality provides customized rehabilitation
      environments for severely affected stroke patients. This approach may facilitate
      motor learning by progressively challenging the subject in accordance with the
      individual capacity for functional restoration. It might be necessary to apply
      concurrent restorative interventions to translate these improvements into
      relevant functional gains of severely motor impaired patients in activities of
      daily living.

PMID- 27895551
TI  - Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Muller
      Glia Dedifferentiation in a Murine Model of Retinal Injury.
AB  - Muller glia (MG) is the most abundant glial type in the vertebrate retina. Among
      its many functions, it is capable of responding to injury by dedifferentiating,
      proliferating, and differentiating into every cell types lost to damage. This
      regenerative ability is notoriously absent in mammals. We have previously
      reported that cultured mammalian MG undergoes a partial dedifferentiation, but
      fails to fully acquire a progenitor phenotype and differentiate into neurons.
      This might be explained by a mnemonic mechanism comprised by epigenetic traits,
      such as DNA methylation. To achieve a better understanding of this epigenetic
      memory, we studied the expression of pluripotency-associated genes, such as Oct4,
      Nanog, and Lin28, which have been reported as necessary for regeneration in fish,
      at early times after NMDA-induced retinal injury in a mouse experimental model.
      We found that although Oct4 is expressed rapidly after damage (4 hpi), it is
      silenced at 24 hpi. This correlates with a significant decrease in the DNA
      methyltransferase Dnmt3b expression, which returns to basal levels at 24 hpi. By
      MS-PCR, we observed a decrease in Oct4 methylation levels at 4 and 12 hpi, before
      returning to a fully methylated state at 24 hpi. To demonstrate that these
      changes are restricted to MG, we separated these cells using a GLAST antibody
      coupled with magnetic beads. Finally, intravitreous administration of the DNA
      methyltransferase inhibitor SGI-1027 induced Oct4 expression at 24 hpi in MG. Our
      results suggest that mammalian MG injury-induced dedifferentiation could be
      restricted by DNA methylation, which rapidly silences Oct4 expression, preventing
      multipotency acquisition.

PMID- 27895553
TI  - Glypican 6 Enhances N-Methyl-D-Aspartate Receptor Function in Human-Induced
      Pluripotent Stem Cell-Derived Neurons.
AB  - The in vitro use of neurons that are differentiated from human induced
      pluripotent stem cells (hiPSC-neurons) is expected to improve the prediction
      accuracy of preclinical tests for both screening and safety assessments in drug
      development. To achieve this goal, hiPSC neurons are required to differentiate
      into functional neurons that form excitatory networks and stably express N-methyl
      D-aspartate receptors (NMDARs). Recent studies have identified some astrocyte
      derived factors that are important for the functional maturation of neurons. We
      therefore examined the effects of the astrocyte-derived factor glypican 6 (GPC6)
      on hiPSC-neurons. When we pharmacologically examined which receptor subtypes
      mediate L-glutamate (L-Glu)-induced changes in the intracellular Ca2+
      concentrations in hiPSC neurons using fura-2 Ca2+ imaging, NMDAR-mediated
      responses were not detected through 7 days in vitro (DIV). These cells were also
      not vulnerable to excitotoxicity at 7 DIV. However, a 5-days treatment with GPC6
      from 3 DIV induced an NMDAR-mediated Ca2+ increase in hiPSC-neurons and increased
      the level of NMDARs on the cell surface. We also found that GPC6-treated hiPSC
      neurons became responsive to excitotoxicity. These results suggest that GPC6
      increases the level of functional NMDARs in hiPSC-neurons. Glial factors may play
      a key role in accelerating the functional maturation of hiPSC neurons for drug
      development applications.

PMID- 27895552
TI  - Computational Models of Auditory Scene Analysis: A Review.
AB  - Auditory scene analysis (ASA) refers to the process (es) of parsing the complex
      acoustic input into auditory perceptual objects representing either physical
      sources or temporal sound patterns, such as melodies, which contributed to the
      sound waves reaching the ears. A number of new computational models accounting
      for some of the perceptual phenomena of ASA have been published recently. Here we
      provide a theoretically motivated review of these computational models, aiming to
      relate their guiding principles to the central issues of the theoretical
      framework of ASA. Specifically, we ask how they achieve the grouping and
      separation of sound elements and whether they implement some form of competition
      between alternative interpretations of the sound input. We consider the extent to
      which they include predictive processes, as important current theories suggest
      that perception is inherently predictive, and also how they have been evaluated.
      We conclude that current computational models of ASA are fragmentary in the sense
      that rather than providing general competing interpretations of ASA, they focus
      on assessing the utility of specific processes (or algorithms) for finding the
      causes of the complex acoustic signal. This leaves open the possibility for
      integrating complementary aspects of the models into a more comprehensive theory
      of ASA.

PMID- 27895554
TI  - Systemic Radical Scavenger Treatment of a Mouse Model of Rett Syndrome: Merits
      and Limitations of the Vitamin E Derivative Trolox.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder typically arising
      from spontaneous mutations in the X-chromosomal methyl-CpG binding protein 2
      (MECP2) gene. The almost exclusively female Rett patients show an apparently
      normal development during their first 6-18 months of life. Subsequently,
      cognitive- and motor-impairment, hand stereotypies, loss of learned skills,
      epilepsy and irregular breathing manifest. Early mitochondrial impairment and
      oxidative challenge are considered to facilitate disease progression. Along this
      line, we recently confirmed in vitro that acute treatment with the vitamin E
      derivative Trolox dampens neuronal hyperexcitability, reinstates synaptic
      plasticity, ameliorates cellular redox balance and improves hypoxia tolerance in
      male MeCP2-deficient (Mecp2-/y ) mouse hippocampus. Pursuing these promising
      findings, we performed a preclinical study to define the merit of systemic Trolox
      administration. Blinded, placebo-controlled in vivo treatment of male mice
      started at postnatal day (PD) 10-11 and continued for ~40 days. Compounds
      (vehicle only, 10 mg/kg or 40 mg/kg Trolox) were injected intraperitoneally every
      48 h. Detailed phenotyping revealed that in Mecp2-/y mice, blood glucose levels,
      lipid peroxidation, synaptic short-term plasticity, hypoxia tolerance and certain
      forms of environmental exploration were improved by Trolox. Yet, body weight and
      size, motor function and the rate and regularity of breathing did not improve. In
      conclusion, in vivo Trolox treatment partially ameliorated a subset of symptoms
      of the complex Rett phenotype, thereby confirming a partial merit of the vitamin
      E-derivative based pharmacotherapy. Yet, it also became evident that frequent
      animal handling and the route of drug administration are critical issues to be
      optimized in future trials.

PMID- 27895555
TI  - Spike Timing Rigidity Is Maintained in Bursting Neurons under Pentobarbital
      Induced Anesthetic Conditions.
AB  - Pentobarbital potentiates gamma-aminobutyric acid (GABA)-mediated inhibitory
      synaptic transmission by prolonging the open time of GABAA receptors. However, it
      is unknown how pentobarbital regulates cortical neuronal activities via local
      circuits in vivo. To examine this question, we performed extracellular unit
      recording in rat insular cortex under awake and anesthetic conditions. Not a few
      studies apply time-rescaling theorem to detect the features of repetitive spike
      firing. Similar to these methods, we define an average spike interval locally in
      time using random matrix theory (RMT), which enables us to compare different
      activity states on a universal scale. Neurons with high spontaneous firing
      frequency (>5 Hz) and bursting were classified as HFB neurons (n = 10), and those
      with low spontaneous firing frequency (<10 Hz) and without bursting were
      classified as non-HFB neurons (n = 48). Pentobarbital injection (30 mg/kg)
      reduced firing frequency in all HFB neurons and in 78% of non-HFB neurons. RMT
      analysis demonstrated that pentobarbital increased in the number of neurons with
      repulsion in both HFB and non-HFB neurons, suggesting that there is a correlation
      between spikes within a short interspike interval (ISI). Under awake conditions,
      in 50% of HFB and 40% of non-HFB neurons, the decay phase of normalized
      histograms of spontaneous firing were fitted to an exponential function, which
      indicated that the first spike had no correlation with subsequent spikes. In
      contrast, under pentobarbital-induced anesthesia conditions, the number of non
      HFB neurons that were fitted to an exponential function increased to 80%, but
      almost no change in HFB neurons was observed. These results suggest that under
      both awake and pentobarbital-induced anesthetized conditions, spike firing in HFB
      neurons is more robustly regulated by preceding spikes than by non-HFB neurons,
      which may reflect the GABAA receptor-mediated regulation of cortical activities.
      Whole-cell patch-clamp recording in the IC slice preparation was performed to
      compare the regularity of spike timing between pyramidal and fast-spiking (FS)
      neurons, which presumably correspond to non-HFB and HFB neurons, respectively.
      Repetitive spike firing of FS neurons exhibited a lower variance of ISI than
      pyramidal neurons both in control and under application of pentobarbital,
      supporting the above hypothesis.

PMID- 27895557
TI  - A Framework for Combining rTMS with Behavioral Therapy.
AB  - Upon its inception, repetitive transcranial magnetic stimulation (rTMS) was
      delivered at rest, without regard to the potential impact of activity occurring
      during or around the time of stimulation. rTMS was considered an experimental
      intervention imposed on the brain; therefore, the myriad features that might
      suppress or enhance its desired effects had not yet been explored. The field of
      rTMS has since grown substantially and therapeutic benefits have been reported,
      albeit with modest and inconsistent improvements. Work in this field accelerated
      following approval of a psychiatric application (depression), and it is now
      expanding to other applications and disciplines. In the last decade, experimental
      enquiry has sought new ways to improve the therapeutic benefits of rTMS, intended
      to enhance underlying brain reorganization and functional recovery by combining
      it with behavioral therapy. This concept is appealing, but poorly defined and
      requires clarity. We provide an overview of how combined rTMS and behavioral
      therapy has been delineated in the literature, highlighting the diversity of
      approaches. We outline a framework for study design and reporting such that the
      effects of this emerging method can be better understood.

PMID- 27895556
TI  - Neurosensory Differentiation and Innervation Patterning in the Human Fetal
      Vestibular End Organs between the Gestational Weeks 8-12.
AB  - Balance orientation depends on the precise operation of the vestibular end organs
      and the vestibular ganglion neurons. Previous research on the assemblage of the
      neuronal network in the developing fetal vestibular organ has been limited to
      data from animal models. Insights into the molecular expression profiles and
      signaling moieties involved in embryological development of the human fetal inner
      ear have been limited. We present an investigation of the cells of the vestibular
      end organs with specific focus on the hair cell differentiation and innervation
      pattern using an uninterrupted series of unique specimens from gestational weeks
      8-12. Nerve fibers positive for peripherin innervate the entire fetal crista and
      utricle. While in rodents only the peripheral regions of the cristae and the
      extra-striolar region of the statolithic organs are stained. At week 9,
      transcription factors PAX2 and PAX8 were observed in the hair cells whereas PAX6
      was observed for the first time among the supporting cells of the cristae and the
      satellite glial cells of the vestibular ganglia. Glutamine synthetase, a
      regulator of the neurotransmitter glutamate, is strongly expressed among
      satellite glia cells, transitional zones of the utricle and supporting cells in
      the sensory epithelium. At gestational week 11, electron microscopic examination
      reveals bouton contacts at hair cells and first signs of the formation of a
      protocalyx at type I hair cells. Our study provides first-hand insight into the
      fetal development of the vestibular end organs as well as their pattern of
      innervation by means of immunohistochemical and EM techniques, with the aim of
      contributing toward our understanding of balance development.

PMID- 27895558
TI  - Physics of the Mind.
AB  - Is it possible to turn psychology into "hard science"? Physics of the mind
      follows the fundamental methodology of physics in all areas where physics have
      been developed. What is common among Newtonian mechanics, statistical physics,
      quantum physics, thermodynamics, theory of relativity, astrophysics... and a
      theory of superstrings? The common among all areas of physics is a methodology of
      physics discussed in the first few lines of the paper. Is physics of the mind
      possible? Is it possible to describe the mind based on the few first principles
      as physics does? The mind with its variabilities and uncertainties, the mind from
      perception and elementary cognition to emotions and abstract ideas, to high
      cognition. Is it possible to turn psychology and neuroscience into "hard"
      sciences? The paper discusses established first principles of the mind, their
      mathematical formulations, and a mathematical model of the mind derived from
      these first principles, mechanisms of concepts, emotions, instincts, behavior,
      language, cognition, intuitions, conscious and unconscious, abilities for
      symbols, functions of the beautiful and musical emotions in cognition and
      evolution. Some of the theoretical predictions have been experimentally
      confirmed. This research won national and international awards. In addition to
      summarizing existing results the paper describes new development theoretical and
      experimental. The paper discusses unsolved theoretical problems as well as
      experimental challenges for future research.

PMID- 27895560
TI  - Neurobiology as Information Physics.
AB  - This article reviews thermodynamic relationships in the brain in an attempt to
      consolidate current research in systems neuroscience. The present synthesis
      supports proposals that thermodynamic information in the brain can be quantified
      to an appreciable degree of objectivity, that many qualitative properties of
      information in systems of the brain can be inferred by observing changes in
      thermodynamic quantities, and that many features of the brain's anatomy and
      architecture illustrate relatively simple information-energy relationships. The
      brain may provide a unique window into the relationship between energy and
      information.

PMID- 27895559
TI  - Reorganization of Visual Callosal Connections Following Alterations of Retinal
      Input and Brain Damage.
AB  - Vision is a very important sensory modality in humans. Visual disorders are
      numerous and arising from diverse and complex causes. Deficits in visual function
      are highly disabling from a social point of view and in addition cause a
      considerable economic burden. For all these reasons there is an intense effort by
      the scientific community to gather knowledge on visual deficit mechanisms and to
      find possible new strategies for recovery and treatment. In this review, we focus
      on an important and sometimes neglected player of the visual function, the corpus
      callosum (CC). The CC is the major white matter structure in the brain and is
      involved in information processing between the two hemispheres. In particular,
      visual callosal connections interconnect homologous areas of visual cortices,
      binding together the two halves of the visual field. This interhemispheric
      communication plays a significant role in visual cortical output. Here, we will
      first review the essential literature on the physiology of the callosal
      connections in normal vision. The available data support the view that the
      callosum contributes to both excitation and inhibition to the target hemisphere,
      with a dynamic adaptation to the strength of the incoming visual input. Next, we
      will focus on data showing how callosal connections may sense visual alterations
      and respond to the classical paradigm for the study of visual plasticity, i.e.,
      monocular deprivation (MD). This is a prototypical example of a model for the
      study of callosal plasticity in pathological conditions (e.g., strabismus and
      amblyopia) characterized by unbalanced input from the two eyes. We will also
      discuss the findings of callosal alterations in blind subjects. Noteworthy, we
      will discuss data showing that inter-hemispheric transfer mediates recovery of
      visual responsiveness following cortical damage. Finally, we will provide an
      overview of how callosal projections dysfunction could contribute to pathologies
      such as neglect and occipital epilepsy. A particular focus will be on reviewing
      noninvasive brain stimulation techniques and optogenetic approaches that allow to
      selectively manipulate callosal function and to probe its involvement in cortical
      processing and plasticity. Overall, the data indicate that experience can
      potently impact on transcallosal connectivity, and that the callosum itself is
      crucial for plasticity and recovery in various disorders of the visual pathway.

PMID- 27895561
TI  - Evidence of a Role for the Lateral Hypothalamic Area Juxtadorsomedial Region
      (LHAjd) in Defensive Behaviors Associated with Social Defeat.
AB  - Our understanding of the extrinsic connections of the lateral hypothalamic area
      (LHA) has deepened in recent years. In particular, a series of studies using
      neural pathway-tracing methods to investigate the macroconnections of
      histologically differentiated LHA regions, have revealed that the neural
      connections of these regions are substantially distinct, and have robust
      connections with neural circuits controlling survival behaviors. To begin testing
      functional associations suggested by the distinct LHA region neural connections,
      the present study has investigated the role of the LHA juxtadorsomedial region
      (LHAjd) in the control of social defeat (a socially-relevant defensive behavior).
      Male rats received bilateral cytotoxic lesions targeted to the LHAjd. A resident
      intruder paradigm was then employed to investigate the effect of these lesions on
      defensive behavioral responses. Behavioral data were collected during three
      phases of testing: (1) pre-encounter habituation to testing context; (2)
      encounter with a dominant conspecific in the testing context; and (3) post
      encounter context. Statistical analysis of behavioral measures revealed a
      significant decrease in risk assessment behaviors during post-encounter context
      testing in lesioned intruders compared to sham-lesioned and intact rats. However,
      changes in defensive behavioral measures during the habituation, or during
      resident-intruder encounters, did not reach significance. We discuss these data
      in relation to LHAjd (and neighboring LHA region) neural connections, and in
      relation to current advances in understanding of the neural control of defensive
      behaviors. A refined model for the neural circuits that are central to the
      control of socially-relevant defensive behaviors is outlined. We also consider
      possible broader implications of these data for disorders of behavioral control.

PMID- 27895563
TI  - The Attentional Dependence of Emotion Cognition Is Variable with the Competing
      Task.
AB  - The relationship between emotion and attention has fascinated researchers for
      decades. Many previous studies have used eye-tracking, ERP, MEG, and fMRI to
      explore this issue but have reached different conclusions: some researchers hold
      that emotion cognition is an automatic process and independent of attention,
      while some others believed that emotion cognition is modulated by attentional
      resources and is a type of controlled processing. The present research aimed to
      investigate this controversy, and we hypothesized that the attentional dependence
      of emotion cognition is variable with the competing task. Eye-tracking technology
      and a dual-task paradigm were adopted, and subjects' attention was manipulated to
      fixate at the central task to investigate whether subjects could detect the
      emotional faces presented in the peripheral area with a decrease or near-absence
      of attention. The results revealed that when the peripheral task was emotional
      face discrimination but the central attention-demanding task was different,
      subjects performed well in the peripheral task, which means that emotional
      information can be processed in parallel with other stimuli, and there may be a
      specific channel in the human brain for processing emotional information.
      However, when the central and peripheral tasks were both emotional face
      discrimination, subjects could not perform well in the peripheral task,
      indicating that the processing of emotional information required attentional
      resources and that it is a type of controlled processing. Therefore, we concluded
      that the attentional dependence of emotion cognition varied with the competing
      task.

PMID- 27895564
TI  - Neural Systems Underlying Emotional and Non-emotional Interference Processing: An
      ALE Meta-Analysis of Functional Neuroimaging Studies.
AB  - Understanding how the nature of interference might influence the recruitments of
      the neural systems is considered as the key to understanding cognitive control.
      Although, interference processing in the emotional domain has recently attracted
      great interest, the question of whether there are separable neural patterns for
      emotional and non-emotional interference processing remains open. Here, we
      performed an activation likelihood estimation meta-analysis of 78 neuroimaging
      experiments, and examined common and distinct neural systems for emotional and
      non-emotional interference processing. We examined brain activation in three
      domains of interference processing: emotional verbal interference in the face
      word conflict task, non-emotional verbal interference in the color-word Stroop
      task, and non-emotional spatial interference in the Simon, SRC and Flanker tasks.
      Our results show that the dorsal anterior cingulate cortex (ACC) was recruited
      for both emotional and non-emotional interference. In addition, the right
      anterior insula, presupplementary motor area (pre-SMA), and right inferior
      frontal gyrus (IFG) were activated by interference processing across both
      emotional and non-emotional domains. In light of these results, we propose that
      the anterior insular cortex may serve to integrate information from different
      dimensions and work together with the dorsal ACC to detect and monitor conflicts,
      whereas pre-SMA and right IFG may be recruited to inhibit inappropriate
      responses. In contrast, the dorsolateral prefrontal cortex (DLPFC) and posterior
      parietal cortex (PPC) showed different degrees of activation and distinct
      lateralization patterns for different processing domains, which suggests that
      these regions may implement cognitive control based on the specific task
      requirements.

PMID- 27895562
TI  - Brain Computation Is Organized via Power-of-Two-Based Permutation Logic.
AB  - There is considerable scientific interest in understanding how cell assemblies
      the long-presumed computational motif-are organized so that the brain can
      generate intelligent cognition and flexible behavior. The Theory of Connectivity
      proposes that the origin of intelligence is rooted in a power-of-two-based
      permutation logic (N = 2 i -1), producing specific-to-general cell-assembly
      architecture capable of generating specific perceptions and memories, as well as
      generalized knowledge and flexible actions. We show that this power-of-two-based
      permutation logic is widely used in cortical and subcortical circuits across
      animal species and is conserved for the processing of a variety of cognitive
      modalities including appetitive, emotional and social information. However,
      modulatory neurons, such as dopaminergic (DA) neurons, use a simpler logic
      despite their distinct subtypes. Interestingly, this specific-to-general
      permutation logic remained largely intact although NMDA receptors-the synaptic
      switch for learning and memory-were deleted throughout adulthood, suggesting that
      the logic is developmentally pre-configured. Moreover, this computational logic
      is implemented in the cortex via combining a random-connectivity strategy in
      superficial layers 2/3 with nonrandom organizations in deep layers 5/6. This
      randomness of layers 2/3 cliques-which preferentially encode specific and low
      combinatorial features and project inter-cortically-is ideal for maximizing cross
      modality novel pattern-extraction, pattern-discrimination and pattern
      categorization using sparse code, consequently explaining why it requires
      hippocampal offline-consolidation. In contrast, the nonrandomness in layers 5/6
      which consists of few specific cliques but a higher portion of more general
      cliques projecting mostly to subcortical systems-is ideal for feedback-control of
      motivation, emotion, consciousness and behaviors. These observations suggest that
      the brain's basic computational algorithm is indeed organized by the power-of-two
      based permutation logic. This simple mathematical logic can account for brain
      computation across the entire evolutionary spectrum, ranging from the simplest
      neural networks to the most complex.

PMID- 27895565
TI  - Challenges to the Pair Bond: Neural and Hormonal Effects of Separation and
      Reunion in a Monogamous Primate.
AB  - Social monogamy at its most basic is a group structure in which two adults form a
      unit and share a territory. However, many socially monogamous pairs display
      attachment relationships known as pair bonds, in which there is a mutual
      preference for the partner and distress upon separation. The neural and hormonal
      basis of this response to separation from the adult pair mate is under-studied.
      In this project, we examined this response in male titi monkeys (Callicebus
      cupreus), a socially monogamous New World primate. Males underwent a baseline
      scan, a short separation (48 h), a long separation (approximately 2 weeks), a
      reunion with the female pair mate and an encounter with a female stranger (with
      nine males completing all five conditions). Regional cerebral glucose metabolism
      was measured via positron emission tomography (PET) imaging using [18F]
      fluorodeoxyglucose (FDG) co-registered with structural magnetic resonance imaging
      (MRI), and region of interest (ROI) analysis was carried out. In addition, plasma
      was collected and assayed for cortisol, oxytocin (OT), vasopressin (AVP), glucose
      and insulin concentrations. Cerebrospinal fluid (CSF) was collected and assayed
      for OT and AVP. We used generalized estimating equations (GEE) to examine
      significant changes from baseline. Short separations were characterized by
      decreases in FDG uptake, in comparison to baseline, in the lateral septum (LS),
      ventral pallidum (VP), paraventricular nucleus of the hypothalamus (PVN),
      periaqueductal gray (PAG), and cerebellum, as well as increases in CSF OT, and
      plasma cortisol and insulin. Long separations differed from baseline in reduced
      FDG uptake in the central amygdala (CeA), reduced whole brain FDG uptake,
      increased CSF OT and increased plasma insulin. The response on encounter with a
      stranger female depended on whether or not the male had previously reproduced
      with his pair mate, suggesting that transitions to fatherhood contribute to the
      neurobiology underlying response to a novel female. Reunion with the partner
      appeared to stimulate coordinated release of central and peripheral OT. The
      observed changes suggest the involvement of OT and AVP systems, as well as limbic
      and striatal areas, during separation and reunion from the pair mate.

PMID- 27895568
TI  - Feasibility of a Mobile Cognitive Intervention in Childhood Absence Epilepsy.
AB  - Children with childhood absence epilepsy (CAE) frequently present with cognitive
      comorbidities and school performance concerns. The present study evaluated the
      feasibility of an intervention for such comorbidities using a mobile cognitive
      therapy application on an iPad. Eight children with CAE and school concerns aged
      7-11 participated in a 4-week intervention. They were asked to use the
      application for 80 min per week (20 min/day, 4 times/week). Parents and children
      completed satisfaction surveys regarding the application. Participants were
      evaluated before and after the intervention using the Cognitive Domain of the NIH
      Toolbox and by parental completion of the Behavioral Rating Inventory of
      Executive Function. All eight patients completed the study, using the iPad for an
      average of 78 min/week. Children and parents reported high satisfaction with the
      application. Though a demonstration of efficacy was not the focus of the study,
      performance improvements were noted on a processing speed task and on a measure
      of fluid intelligence. An iPad based cognitive therapy was found to be a feasible
      intervention for children with CAE.

PMID- 27895567
TI  - Cognitive Processing in Non-Communicative Patients: What Can Event-Related
      Potentials Tell Us?
AB  - Event-related potentials (ERP) have been proposed to improve the differential
      diagnosis of non-responsive patients. We investigated the potential of the P300
      as a reliable marker of conscious processing in patients with locked-in syndrome
      (LIS). Eleven chronic LIS patients and 10 healthy subjects (HS) listened to a
      complex-tone auditory oddball paradigm, first in a passive condition (listen to
      the sounds) and then in an active condition (counting the deviant tones). Seven
      out of nine HS displayed a P300 waveform in the passive condition and all in the
      active condition. HS showed statistically significant changes in peak and area
      amplitude between conditions. Three out of seven LIS patients showed the P3
      waveform in the passive condition and five of seven in the active condition. No
      changes in peak amplitude and only a significant difference at one electrode in
      area amplitude were observed in this group between conditions. We conclude that,
      in spite of keeping full consciousness and intact or nearly intact cortical
      functions, compared to HS, LIS patients present less reliable results when
      testing with ERP, specifically in the passive condition. We thus strongly
      recommend applying ERP paradigms in an active condition when evaluating
      consciousness in non-responsive patients.

PMID- 27895569
TI  - Influence of Lumbar Muscle Fatigue on Trunk Adaptations during Sudden External
      Perturbations.
AB  - Introduction: When the spine is subjected to perturbations, neuromuscular
      responses such as reflex muscle contractions contribute to the overall balance
      control and spinal stabilization mechanisms. These responses are influenced by
      muscle fatigue, which has been shown to trigger changes in muscle recruitment
      patterns. Neuromuscular adaptations, e.g., attenuation of reflex activation
      and/or postural oscillations following repeated unexpected external
      perturbations, have also been described. However, the characterization of these
      adaptations still remains unclear. Using high-density electromyography (EMG) may
      help understand how the nervous system chooses to deal with an unknown
      perturbation in different physiological and/or mechanical perturbation
      environments. Aim: To characterize trunk neuromuscular adaptations following
      repeated sudden external perturbations after a back muscle fatigue task using
      high-density EMG. Methods: Twenty-five healthy participants experienced a series
      of 15 sudden external perturbations before and after back muscle fatigue. Erector
      spinae muscle activity was recorded using high-density EMG. Trunk kinematics
      during perturbation trials were collected using a 3-D motion analysis system. A
      two-way repeated measure ANOVA was conducted to assess: (1) the adaptation effect
      across trials; (2) the fatigue effect; and (3) the interaction effect (fatigue *
      adaptation) for the baseline activity, the reflex latency, the reflex peak and
      trunk kinematic variables (flexion angle, velocity and time to peak velocity).
      Muscle activity spatial distribution before and following the fatigue task was
      also compared using t-tests for dependent samples. Results: An attenuation of
      muscle reflex peak was observed across perturbation trials before the fatigue
      task, but not after. The spatial distribution of muscle activity was
      significantly higher before the fatigue task compared to post-fatigue trials.
      Baseline activity showed a trend to higher values after muscle fatigue, as well
      as reduction through perturbation trials. Main effects of fatigue and adaptation
      were found for time to peak velocity. No adaptation nor fatigue effect were
      identified for reflex latency, flexion angle or trunk velocity. Conclusion: The
      results show that muscle fatigue leads to reduced spatial distribution of back
      muscle activity and suggest a limited ability to use across-trial redundancy to
      adapt EMG reflex peak and optimize spinal stabilization using retroactive
      control.

PMID- 27895566
TI  - Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced
      Fatigue and Depression.
AB  - This paper outlines a hierarchical Bayesian framework for interoception,
      homeostatic/allostatic control, and meta-cognition that connects fatigue and
      depression to the experience of chronic dyshomeostasis. Specifically, viewing
      interoception as the inversion of a generative model of viscerosensory inputs
      allows for a formal definition of dyshomeostasis (as chronically enhanced
      surprise about bodily signals, or, equivalently, low evidence for the brain's
      model of bodily states) and allostasis (as a change in prior beliefs or
      predictions which define setpoints for homeostatic reflex arcs). Critically, we
      propose that the performance of interoceptive-allostatic circuitry is monitored
      by a metacognitive layer that updates beliefs about the brain's capacity to
      successfully regulate bodily states (allostatic self-efficacy). In this
      framework, fatigue and depression can be understood as sequential responses to
      the interoceptive experience of dyshomeostasis and the ensuing metacognitive
      diagnosis of low allostatic self-efficacy. While fatigue might represent an early
      response with adaptive value (cf. sickness behavior), the experience of chronic
      dyshomeostasis may trigger a generalized belief of low self-efficacy and lack of
      control (cf. learned helplessness), resulting in depression. This perspective
      implies alternative pathophysiological mechanisms that are reflected by
      differential abnormalities in the effective connectivity of circuits for
      interoception and allostasis. We discuss suitably extended models of effective
      connectivity that could distinguish these connectivity patterns in individual
      patients and may help inform differential diagnosis of fatigue and depression in
      the future.

PMID- 27895570
TI  - Sex Differences in Gray Matter Volume of the Right Anterior Hippocampus Explain
      Sex Differences in Three-Dimensional Mental Rotation.
AB  - Behavioral studies have reported that males perform better than females in 3
      dimensional (3D) mental rotation. Given the important role of the hippocampus in
      spatial processing, the present study investigated whether structural differences
      in the hippocampus could explain the sex difference in 3D mental rotation.
      Results showed that after controlling for brain size, males had a larger anterior
      hippocampus, whereas females had a larger posterior hippocampus. Gray matter
      volume (GMV) of the right anterior hippocampus was significantly correlated with
      3D mental rotation score. After controlling GMV of the right anterior
      hippocampus, sex difference in 3D mental rotation was no longer significant.
      These results suggest that the structural difference between males' and females'
      right anterior hippocampus was a neurobiological substrate for the sex difference
      in 3D mental rotation.

PMID- 27895571
TI  - Neural Mechanisms of Positive Mood Induced Modulation of Reality Monitoring.
AB  - This study investigates the neural mechanisms of mood induced modulation of
      cognition, specifically, on reality monitoring abilities. Reality monitoring is
      the ability to accurately distinguish the source of self-generated information
      from externally-presented contextual information. When participants were in a
      positive mood, compared to a neutral mood, they significantly improved their
      source memory identification abilities, particularly for self-generated
      information. However, being in a negative mood had no effect on reality
      monitoring abilities. Additionally, when participants were in a positive mood
      state, they showed activation in several regions that predisposed them to perform
      better at reality monitoring. Specifically, positive mood induced activity within
      the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) was
      associated with improvements in subsequent identification of self-generated
      information, and positive mood induced activation within the striatum (putamen)
      facilitated better identification of externally-presented information. These
      findings indicate that regions within mPFC, PCC and striatum are sensitive to
      positive mood-cognition enhancing effects that enable participants to be better
      prepared for subsequent reality monitoring decision-making.

PMID- 27895572
TI  - Plastic Changes in Human Motor Cortical Output Induced by Random but not Closed
      Loop Peripheral Stimulation: the Curse of Causality.
AB  - Previous work showed that repetitive peripheral nerve stimulation can induce
      plastic changes in motor cortical output. Triggering electrical stimulation of
      central structures from natural activity can also generate plasticity. In this
      study, we tested whether triggering peripheral nerve stimulation from muscle
      activity would likewise induce changes in motor output. We developed a wearable
      electronic device capable of recording electromyogram (EMG) and delivering
      electrical stimulation under closed-loop control. This allowed paired stimuli to
      be delivered over longer periods than standard laboratory-based protocols. We
      tested this device in healthy human volunteers. Motor cortical output in relaxed
      thenar muscles was first assessed via the recruitment curve of responses to
      contralateral transcranial magnetic stimulation. The wearable device was then
      configured to record thenar EMG and stimulate the median nerve at the wrist
      (intensity around motor threshold, rate ~0.66 Hz). Subjects carried out normal
      daily activities for 4-7 h, before returning to the laboratory for repeated
      recruitment curve assessment. Four stimulation protocols were tested (9-14
      subjects each): No Stim, no stimuli delivered; Activity, stimuli triggered by EMG
      activity above threshold; Saved, stimuli timed according to a previous Activity
      session in the same subject; Rest, stimuli given when EMG was silent. As
      expected, No Stim did not modify the recruitment curve. Activity and Rest
      conditions produced no significant effects across subjects, although there were
      changes in some individuals. Saved produced a significant and substantial
      increase, with average responses 2.14 times larger at 30% stimulator intensity
      above threshold. We argue that unavoidable delays in the closed loop feedback,
      due mainly to central and peripheral conduction times, mean that stimuli in the
      Activity paradigm arrived too late after cortical activation to generate
      consistent plastic changes. By contrast, stimuli delivered essentially at random
      during the Saved paradigm may have caused a generalized increase in cortical
      excitability akin to stochastic resonance, leading to plastic changes in
      corticospinal output. Our study demonstrates that non-invasive closed loop
      stimulation may be critically limited by conduction delays and the unavoidable
      constraint of causality.

PMID- 27895574
TI  - Robot-Assisted Rehabilitation of Ankle Plantar Flexors Spasticity: A 3-Month
      Study with Proprioceptive Neuromuscular Facilitation.
AB  - In this paper, we aim to investigate the effect of proprioceptive neuromuscular
      facilitation (PNF)-based rehabilitation for ankle plantar flexors spasticity by
      using a Robotic Ankle-foot Rehabilitation System (RARS). A modified robot
      assisted system was proposed, and seven poststroke patients with hemiplegic
      spastic ankles participated in a 3-month robotic PNF training. Their impaired
      sides were used as the experimental group, while their unimpaired sides as the
      control group. A robotic intervention for the experimental group started from a 2
      min passive stretching to warming-up or relaxing the soleus and gastrocnemius
      muscles and also ended with the same one. Then a PNF training session including
      30 trials was activated between them. The rehabilitation trainings were carried
      out three times a week as an addition to their regular rehabilitation exercise.
      Passive range of motion, resistance torque, and stiffness were measured in both
      ankles before and after the interventions. The changes in Achilles tendon length,
      walking speed, and lower limb function were also evaluated by the same physician
      or physiotherapist for each participant. Biomechanical measurements before
      interventions showed significant difference between the experimental group and
      the control group due to ankle spasticity. For the control group, there was no
      significant difference in the 3 months with no robotic intervention. But for the
      experimental group, passive dorsiflexion range of motion increased (p < 0.01),
      resistance torque under different dorsiflexion angle levels (0 degrees , 10
      degrees , and 20 degrees ) decreased (p < 0.05, p < 0.001, and p < 0.001,
      respectively), and quasi-static stiffness under different dorsiflexion angle
      levels (0 degrees , 10 degrees , and 20 degrees ) also decreased (p < 0.01, p <
      0.001, and p < 0.001, respectively). Achilles's tendon length shortened (p <
      0.01), while its thickness showed no significant change (p > 0.05). The robotic
      rehabilitation also improved the muscle strength (p < 0.01) and muscle control
      performance (p < 0.001). In addition, improvements were observed in clinical and
      functional measurements, such as Timed Up-and-Go (p < 0.05), normal walking speed
      (p > 0.05), and fast walking speed (p < 0.05). These results indicated that the
      PNF-based robotic intervention could significantly alleviate lower limb
      spasticity and improve the motor function in chronic stroke participant. The
      robotic system could potentially be used as an effective tool in poststroke
      rehabilitation training.

PMID- 27895573
TI  - Prediction Signatures in the Brain: Semantic Pre-Activation during Language
      Comprehension.
AB  - There is broad agreement that context-based predictions facilitate lexical
      semantic processing. A robust index of semantic prediction during language
      comprehension is an evoked response, known as the N400, whose amplitude is
      modulated as a function of semantic context. However, the underlying neural
      mechanisms that utilize relations of the prior context and the embedded word
      within it are largely unknown. We measured magnetoencephalography (MEG) data
      while participants were listening to simple German sentences in which the verbs
      were either highly predictive for the occurrence of a particular noun (i.e.,
      provided context) or not. The identical set of nouns was presented in both
      conditions. Hence, differences for the evoked responses of the nouns can only be
      due to differences in the earlier context. We observed a reduction of the N400
      response for highly predicted nouns. Interestingly, the opposite pattern was
      observed for the preceding verbs: highly predictive (that is more informative)
      verbs yielded stronger neural magnitude compared to less predictive verbs. A
      negative correlation between the N400 effect of the verb and that of the noun was
      found in a distributed brain network, indicating an integral relation between the
      predictive power of the verb and the processing of the subsequent noun. This
      network consisted of left hemispheric superior and middle temporal areas and a
      subcortical area; the parahippocampus. Enhanced activity for highly predictive
      relative to less predictive verbs, likely reflects establishing semantic features
      associated with the expected nouns, that is a pre-activation of the expected
      nouns.

PMID- 27895575
TI  - Can Animal Models Contribute to Understanding Tinnitus Heterogeneity in Humans?
AB  - The brain activity of humans with tinnitus of various etiologies is typically
      studied with electro- and magneto-encephalography and functional magnetic
      resonance imaging-based imaging techniques. Consequently, they measure population
      responses and mostly from the neocortex. The latter also underlies changes in
      neural networks that may be attributed to tinnitus. However, factors not strictly
      related to tinnitus such as hearing loss and hyperacusis, as well as other co
      occurring disorders play a prominent role in these changes. Different types of
      tinnitus can often not be resolved with these brain-imaging techniques. In animal
      models of putative behavioral signs of tinnitus, neural activity ranging from
      auditory nerve to auditory cortex, is studied largely by single unit recordings,
      augmented by local field potentials (LFPs), and the neural correlates of tinnitus
      are mainly based on spontaneous neural activity, such as spontaneous firing rates
      and pair-wise spontaneous spike-firing correlations. Neural correlates of
      hyperacusis rely on measurement of stimulus-evoked activity and are measured as
      increased driven firing rates and LFP amplitudes. Connectivity studies would rely
      on correlated neural activity between pairs of neurons or LFP amplitudes, but are
      only recently explored. In animal models of tinnitus, only two etiologies are
      extensively studied; tinnitus evoked by salicylate application and by noise
      exposure. It appears that they have quite different neural biomarkers. The
      unanswered question then is: does this different etiology also result in
      different tinnitus?

PMID- 27895576
TI  - Sleep Disturbances among Older Adults in the United States, 2002-2012: Nationwide
      Inpatient Rates, Predictors, and Outcomes.
AB  - Objective/Background: We examined the rates, predictors, and outcomes [mortality
      risk (MR), length of stay (LOS), and total charges (TC)] of sleep disturbances in
      older hospitalized patients. Patients/Methods: Using the U.S. Nationwide
      Inpatient Sample database (2002-2012), older patients (>=60 years) were selected
      and rates of insomnia, obstructive sleep apnea (OSA) and other sleep disturbances
      (OSD) were estimated using ICD-9CM. TC, adjusted for inflation, was of primary
      interest, while MR and LOS were secondary outcomes. Multivariable regression
      analyses were conducted. Results: Of 35,258,031 older adults, 263,865 (0.75%) had
      insomnia, 750,851 (2.13%) OSA and 21,814 (0.06%) OSD. Insomnia rates increased
      significantly (0.27% in 2002 to 1.29 in 2012, P-trend < 0.001), with a similar
      trend observed for OSA (1.47 in 2006 to 5.01 in 2012, P-trend < 0.001). TC (2012
      $) for insomnia-related hospital admission increased over time from $22,250 in
      2002 to $31,527 in 2012, and increased similarly for OSA and OSD; while LOS and
      MR both decreased. Women with any sleep disturbance had lower MR and TC than men,
      while Whites had consistently higher odds of insomnia, OSA, and OSD than older
      Blacks and Hispanics. Co-morbidities such as depression, cardiovascular risk
      factors, and neurological disorders steadily increased over time in patients with
      sleep disturbances. Conclusion: TC increased over time in patients with sleep
      disturbances while LOS and MR decreased. Further, research should focus on
      identifying the mechanisms that explain the association between increasing sleep
      disturbance rates and expenditures within hospital settings and the potential
      hospital expenditures of unrecognized sleep disturbances in the elderly.

PMID- 27895578
TI  - Cognitive Performance Patterns in Healthy Individuals with Substantia Nigra
      Hyperechogenicity and Early Parkinson's Disease.
AB  - Introduction: Hyperechogenicity of the substantia nigra (SN+) is a risk marker
      for Parkinson's disease (PD) which can be detected before the diagnosis. In
      healthy individuals, SN+ has been associated with slight deficits in specific
      cognitive functions, suggesting cognitive impairment as a possible pre-diagnostic
      marker for PD. However, the pattern of cognitive deficits associated with SN+ has
      not yet been compared with those present in PD. Methods: Data of 262 healthy
      individuals with normal echogenicity (SN-) and 48 healthy individuals with SN+
      were compared with 82 early stage PD patients using the "Consortium to Establish
      a Registry for Alzheimer's disease" test battery. First, the test clusters
      (factors) were identified using a principal component analysis (PCA). Mean group
      performance of cognitive tests belonging to distinct factors, according to the
      PCA, and single subtest performances were compared using analyses of variance.
      Second, the number of individuals with abnormal cognitive performances (z-score <
      -1.0) were compared between groups. Results: Verbal memory, semantic and
      executive function, and praxis were identified as components of cognitive
      performances. The SN+ group performed significantly worse than the SN- group in
      tests assessing semantic and executive function, with a non-significant decrease
      in verbal memory. On the subtest level, individuals of the SN+ group scored
      significantly lower than the SN- group on the Boston Naming Test (BNT; p =
      0.008). In all subtests, the percentages of PD patients with values below the cut
      off for abnormal performance were higher than in the SN- group. Moreover, more
      individuals from the SN+ group scored below the cut-off in the BNT (SN- = 8.4%,
      SN+ = 20.8%, p = 0.01) and TMT-B (SN- = 6.9%, SN+ = 16.7%, p = 0.02), compared to
      the SN- group. Conclusion: This study confirms poorer performance of healthy
      individuals with SN+ compared to SN- in specific cognitive domains. However,
      against the SN- group, the cognitive profile of the SN+ group was not fully
      consistent with the profile of early PD patients. Our data argues that cognitive
      impairment associated with SN+ might differ slightly from that seen in early PD.
      Compensational mechanisms in the early phases of neurodegeneration, and the fact
      that only a subgroup of SN+ will develop PD, may partly explain these
      differences.

PMID- 27895577
TI  - Fus1 KO Mouse As a Model of Oxidative Stress-Mediated Sporadic Alzheimer's
      Disease: Circadian Disruption and Long-Term Spatial and Olfactory Memory
      Impairments.
AB  - Insufficient advances in the development of effective therapeutic treatments of
      sporadic Alzheimer's Disease (sAD) to date are largely due to the lack of sAD
      relevant animal models. While the vast majority of models do recapitulate AD's
      hallmarks of plaques and tangles by virtue of tau and/or beta amyloid
      overexpression, these models do not reflect the fact that in sAD (unlike familial
      AD) these genes are not risk factors per se and that other mechanisms like
      oxidative stress, metabolic dysregulation and inflammation play key roles in AD
      etiology. Here we characterize and propose the Fus1 KO mice that lack a
      mitochondrial protein Fus1/Tusc2 as a new sAD model. To establish sAD relevance,
      we assessed sAD related deficits in Fus1 KO and WT adult mice of 4-5 months old,
      the equivalent human age when the earliest cognitive and olfactory sAD symptoms
      arise. Fus1 KO mice showed oxidative stress (increased levels of ROS, decreased
      levels of PRDX1), disruption of metabolic homeostasis (decreased levels of ACC2,
      increased phosphorylation of AMPK), autophagy (decreased levels of LC3-II), PKC
      (decreased levels of RACK1) and calcium signaling (decreased levels of Calb2) in
      the olfactory bulb and/or hippocampus. Mice were behaviorally tested using
      objective and accurate video tracking (Noldus), in which Fus1 KO mice showed
      clear deficits in olfactory memory (decreased habituation/cross-habituation in
      the short and long term), olfactory guided navigation memory (inability to reduce
      their latency to find the hidden cookie), spatial memory (learning impairments on
      finding the platform in the Morris water maze) and showed more sleep time during
      the diurnal cycle. Fus1 KO mice did not show clear deficits in olfactory
      perception (cross-habituation), association memory (passive avoidance) or in
      species-typical behavior (nest building) and no increased anxiety (open field,
      light-dark box) or depression/anhedonia (sucrose preference) at this relatively
      young age. These neurobehavioral deficits of the Fus1 KO mice at this relatively
      young age are highly relevant to sAD, making them suitable for effective research
      on pharmacological targets in the context of early intervention of sAD.

PMID- 27895580
TI  - Increased Levels of miRNA-146a in Serum and Histologic Samples of Patients with
      Uveal Melanoma.
AB  - Purpose: To analyze MiRs expression in serum of UM patients, respect to healthy
      donors, and to compare this data with MiRs expressed in formalin-fixed, paraffin
      embedded UM samples. Methods: Expression profile of 754 miRNAs was performed in
      serum of patients with uveal melanoma who underwent primary enucleation. The
      level of miRNAs increased in serum was individually analyzed on FFPE UM samples
      and compared to choroidal melanocytes from unaffected eyes. Results: Fourteen
      patients with uveal melanoma were included in the study. We found 8 serum miRNAs
      differentially expressed compared to normal controls: 2 upregulated miRNAs (miRNA
      146a, miR-523); 6 downregulated miRNAs (miR-19a, miR-30d, miR-127, miR-451, miR
      518f, miR-1274B). When data on upregulated miRNAs were singularly validated only
      a significant overexpression of miRNA-146a was found. A statistically significant
      upregulation of miRNA-146a was also found on FFPE UM samples, compared to
      choroidal melanocytes from unaffected eyes. Conclusions: miRNA-146a is increased
      in serum of patients with UM and in FFPE tumor samples. Further studies will show
      if it could be considered a potential marker of UM in the blood.

PMID- 27895581
TI  - Evaluation of Near Infrared Dyes as Markers of P-Glycoprotein Activity in Tumors.
AB  - Aim: The multidrug resistance protein 1 (MDR1; P-glycoprotein) has been
      associated with efflux of chemotherapeutic agents from tumor cells and with poor
      patient prognosis. This study evaluated the feasibility of non-invasive, non
      radioactive near infrared (NIR) imaging methodology for detection of MDR1
      functional activity in tumors. Methods: Initial accumulation assays were
      conducted in MDR1-overexpressing MDCK cells (MDCK-MDR1) and control MDCK cells
      (MDCK-CT) using the NIR dyes indocyanine green (ICG), IR-783, IR-775, rhodamine
      800, XenoLight DiR, and Genhance 750, at 0.4 MUM-100 MUM. ICG and IR-783 were
      also evaluated in HT-29 cells in which MDR1 overexpression was induced by
      colchicine (HT-29-MDR1) and their controls (HT-29-CT). In vivo optical imaging
      studies were conducted using immunodeficient mice bearing HT-29-CT and HT-29-MDR1
      xenografts. Results: ICG's emission intensity was 2.0- and 2.2-fold higher in
      control versus MDR1-overexpressing cells, in MDCK and HT-29 cell lines,
      respectively. The respective IR-783 control:MDR1 ratio was 1.4 in both MDCK and
      HT-29 cells. Optical imaging of mice bearing HT-29-CT and HT-29-MDR1 xenografts
      revealed a statistically non-significant, 1.7-fold difference (p > 0.05) in ICG
      emission intensity between control and MDR1 tumors. No such differences were
      observed with IR-783. Conclusion: ICG and IR-783 appear to be weak MDR1
      substrates. In vivo, low sensitivity and high between-subject variability impair
      the ability to use the currently studied probes as markers of tumor MDR1
      activity. The results suggest that, for future use of this technology, additional
      NIR probes should be screened as MDR1 substrates.

PMID- 27895579
TI  - Pharmacodynamic Modeling of Cell Cycle Effects for Gemcitabine and Trabectedin
      Combinations in Pancreatic Cancer Cells.
AB  - Combinations of gemcitabine and trabectedin exert modest synergistic cytotoxic
      effects on two pancreatic cancer cell lines. Here, systems pharmacodynamic (PD)
      models that integrate cellular response data and extend a prototype model
      framework were developed to characterize dynamic changes in cell cycle phases of
      cancer cell subpopulations in response to gemcitabine and trabectedin as single
      agents and in combination. Extensive experimental data were obtained for two
      pancreatic cancer cell lines (MiaPaCa-2 and BxPC-3), including cell proliferation
      rates over 0-120 h of drug exposure, and the fraction of cells in different cell
      cycle phases or apoptosis. Cell cycle analysis demonstrated that gemcitabine
      induced cell cycle arrest in S phase, and trabectedin induced transient cell
      cycle arrest in S phase that progressed to G2/M phase. Over time, cells in the
      control group accumulated in G0/G1 phase. Systems cell cycle models were
      developed based on observed mechanisms and were used to characterize both cell
      proliferation and cell numbers in the sub G1, G0/G1, S, and G2/M phases in the
      control and drug-treated groups. The proposed mathematical models captured well
      both single and joint effects of gemcitabine and trabectedin. Interaction
      parameters were applied to quantify unexplainable drug-drug interaction effects
      on cell cycle arrest in S phase and in inducing apoptosis. The developed models
      were able to identify and quantify the different underlying interactions between
      gemcitabine and trabectedin, and captured well our large datasets in the
      dimensions of time, drug concentrations, and cellular subpopulations.

PMID- 27895582
TI  - Introduction of an N-Glycosylation Site into UDP-Glucuronosyltransferase 2B3
      Alters Its Sensitivity to Cytochrome P450 3A1-Dependent Modulation.
AB  - Our previous studies have demonstrated functional protein-protein interactions
      between cytochrome P450 (CYP) 3A and UDP-glucuronosyltransferase (UGT). However,
      the role of carbohydrate chains of UGTs in the interaction with CYP is not well
      understood. To address this issue, we examined whether CYP3A1 modulates the
      function of UGT2B3 which lacks potential glycosylation sites. We also examined
      whether the introduction of N-glycosylation to UGT2B3 affects CYP3A-dependent
      modulation of UGT function. To introduce a potential glycosylation site into
      UGT2B3, Ser 316 of UGT2B3 was substituted with Asn by site-directed mutagenesis.
      A baculovirus-Sf-9 cell system for expressing CYP3A1 and UGT2B3/UGT2B3(S316N) was
      established using a Bac-to-Bac system. Glycosylation of UGT2B3(S316N) was
      demonstrated in this expression system. The microsomal activity of recombinant
      UGT was determined using 4-methylumbelliferone as a substrate. The effect of
      CYP3A1 co-expression on UGT function was examined by comparing the kinetic
      profiles between single (UGT alone) and double expression (UGT plus CYP) systems.
      The kinetics of the two expression systems fitted a Michaelis-Menten equation.
      When the 4-MU concentration was varied, co-expression of CYP3A1 lowered the Vmax
      of UGT2B3-mediated conjugation. Conversely, for UGT2B3(S316N), the Vmax in the
      dual expression system was higher than that in the single expression system. The
      data obtained demonstrate that the introduction of N-glycosylation to UGT2B3
      alters its sensitivity to CYP3A1-dependent modulation while CYP3A1 enhanced
      UGT2B3(S316N) activity, and wild-type UGT2B3 was suppressed by CYP3A1. These data
      suggest that N-glycosylation of UGT is one of the determinants regulating the
      interaction between CYP3A and UGT.

PMID- 27895583
TI  - Matching Adherence Interventions to Patient Determinants Using the Theoretical
      Domains Framework.
AB  - Introduction: Despite much research, interventions to improve medication
      adherence report disappointing and inconsistent results. Tailored approaches that
      match interventions and patient determinants of non-adherence were seldom used in
      clinical trials. The presence of a multitude of theoretical frameworks and models
      to categorize interventions and patient determinants complicated the development
      of common categories shared by interventions and determinants. We retrieved
      potential interventions and patient determinants from published literature on
      medication adherence, matched them like locks and keys, and categorized them
      according to the Theoretical Domains Framework (TDF). Methods: We identified the
      most relevant literature reviews on interventions and determinants in a pragmatic
      literature search, extracted all interventions and determinants, grouped similar
      concepts to umbrella terms and assigned them to TDF categories. All steps were
      finalized in consensus discussion between the authors. Results: Sixteen articles
      (5 with determinants, 11 with interventions) were included for analysis. We
      extracted 103 interventions and 42 determinants that we divided in 26 modifiable
      and 16 unmodifiable determinants. All interventions and modifiable determinants
      were matched within 11 categories (Knowledge; Skills; Social/professional role
      and identity; Beliefs about capabilities; Beliefs about consequences; Intentions;
      Memory, Attention and decision processes; Environmental context and resources;
      Social influences; Emotion; and Behavioral regulation). Conclusion: In published
      trials on medication adherence, the congruence between interventions and
      determinants can be assessed with matching interventions to determinants. To be
      successful, interventions in medication adherence should target current
      modifiable determinants and be tailored to the unmodifiable determinants.
      Modifiable and unmodifiable determinants need to be assessed at inclusion of
      intervention studies to identify the patients most in need of an adherence
      intervention. Our matched categories may be useful to develop interventions in
      trials that investigate the effectiveness of adherence interventions.

PMID- 27895585
TI  - Feto-Maternal Trafficking of Exosomes in Murine Pregnancy Models.
AB  - Timing and initiation of labor are well-orchestrated by signals communicated
      between the fetal and maternal compartments; however, how these signals are
      communicated is not completely understood. Fetal exosomes, intercellular
      signaling vesicles, may play a key role in the process. The objective of this
      study was to evaluate exosome trafficking in vivo from fetal to maternal
      compartments. Pregnant CD-1 mice were intra-amniotically injected on gestational
      day 16 and 17 with exosomes isolated from primary human amnion epithelial cells
      fluorescently labeled with the lipophilic dye 1,1-dioctadecyl-3,3,3,3
      tetramethylindotricarbocyanine iodide (DiR). All our analyses were performed on
      samples collected on Day 18. After 24 h, mice were imaged using Bruker MS FX PRO
      In vivo Imager and tissues were collected. In vivo imaging of mouse showed
      fluorescence in the uterus, on the exosome-injected side whereas the uterine
      tissues from the uninjected side and saline and dye alone injected animals
      remained negative. Histological analysis of placenta showed exosome migration
      from the fetal to the maternal side of the placenta. Fluorescence released from
      exosomes was seen in maternal blood samples as well as in maternal uterus and
      kidneys. This study demonstrates that exosomal cargo can be carried through
      systemic route from the fetal to the maternal side of the uterine tissues during
      pregnancy, supporting the idea that fetal signals can be delivered via exosomes.

PMID- 27895584
TI  - Induced Pluripotent Stem Cells Inhibit Bleomycin-Induced Pulmonary Fibrosis in
      Mice through Suppressing TGF-beta1/Smad-Mediated Epithelial to Mesenchymal
      Transition.
AB  - Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with
      high mortality and few treatment options. Recently, induced pluripotent stem
      (iPS) cells have been considered as an ideal resource for stem cell-based
      therapy. Although, an earlier study demonstrated the therapeutic effect of iPS
      cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present
      study investigated the effects of iPS cells on inflammatory responses,
      transforming growth factor (TGF)-beta1 signaling pathway, and epithelial to
      mesenchymal transition (EMT) during bleomycin (BLM)-induced lung fibrosis. A
      single intratracheal instillation of BLM (5 mg/kg) was performed to induce
      pulmonary fibrosis in C57BL/6 mice. Then, iPS cells (c-Myc-free) were
      administrated intravenously at 24 h following BLM instillation. Three weeks after
      BLM administration, pulmonary fibrosis was evaluated. As expected, treatment with
      iPS cells significantly limited the pathological changes, edema, and collagen
      deposition in lung tissues of BLM-induced mice. Mechanically, treatment with iPS
      cells obviously repressed the expression ratios of matrix metalloproteinase-2
      (MMP-2) to its tissue inhibitor -2 (TIMP-2) and MMP-9/TIMP-1 in BLM-induced
      pulmonary tissues. In addition, iPS cell administration remarkably suppressed BLM
      induced up-regulation of pulmonary inflammatory mediators, including tumor
      necrosis factor-alpha, interleukin (IL)-1beta, IL-6, inducible nitric oxide
      synthase, nitric oxide, cyclooxygenase-2 and prostaglandin E2. We further
      demonstrated that transplantation of iPS cells markedly inhibited BLM-mediated
      activation of TGF-beta1/Mothers against decapentaplegic homolog 2/3 (Smad2/3) and
      EMT in lung tissues through up-regulating epithelial marker E-cadherin and down
      regulating mesenchymal markers including fibronectin, vimentin and alpha-smooth
      muscle actin. Moreover, in vitro, iPS cell-conditioned medium (iPSC-CM)
      profoundly inhibited TGF-beta1-induced EMT signaling pathway in mouse alveolar
      epithelial type II cells (AECII). Collectively, our results suggest that
      transplantation of iPS cells could suppress inflammatory responses, TGF
      beta1/Smad2/3 pathway and EMT during the progression of BLM-induced pulmonary
      fibrosis, providing new useful clues regarding the mechanisms of iPS cells in the
      treatment for this disease.

PMID- 27895586
TI  - Weakening Impact of Excessive Human Serum Albumin (eHSA) on Cisplatin and
      Etoposide Anticancer Effect in C57BL/6 Mice with Tumor and in Human NSCLC A549
      Cells.
AB  - Excessive human serum albumin (eHSA) impact on anticancer effects is
      inconsistent. We explored the outcome of cisplatin (DDP)/etoposide (VP-16) plus
      eHSA in vivo and in vitro. C57BL/6 mice with tumor were used to compare the
      efficacy of DDP/VP-16 alone and DDP/VP-16+eHSA. Blood albumin was measured to
      confirm whether eHSA elevate its level. Western blotting assay were used to
      measure the expression of ERCC1/TOP2A in tumor tissues. Cell proliferation, mRNA,
      and protein expression of ERCC1/TOP2A were also assayed to compare two groups in
      A549 cells. Furthermore we evaluated eHSA impact on cell proliferation in RNAi
      targeting ERCC1/TOP2A in A549 cells, respectively. eHSA reduced the anticancer
      effect of DDP/VP-16 without altering albumin level, increased protein expression
      of ERCC1/TOP2A, respectively in mice. Similarly, eHSA increased mRNA and proteins
      expression of ERCC1/TOP2A in A549 cells. In RNAi A549 cells, however, eHSA no
      longer weakened but enhanced the anticancer effect of DDP, while no longer
      altered the effect of VP-16. Our findings suggested that eHSA weaken the
      anticancer effect of DDP/VP-16 via up-regulating ERCC1/TOP2A expression,
      respectively. Further molecular mechanism studies are warranted to investigate
      whether eHSA is not conducive to lung cancer chemotherapy.

PMID- 27895588
TI  - Influence of Heart Rate in Non-linear HRV Indices as a Sampling Rate Effect
      Evaluated on Supine and Standing.
AB  - The purpose of this study is to characterize and attenuate the influence of mean
      heart rate (HR) on nonlinear heart rate variability (HRV) indices (correlation
      dimension, sample, and approximate entropy) as a consequence of being the HR the
      intrinsic sampling rate of HRV signal. This influence can notably alter nonlinear
      HRV indices and lead to biased information regarding autonomic nervous system
      (ANS) modulation. First, a simulation study was carried out to characterize the
      dependence of nonlinear HRV indices on HR assuming similar ANS modulation.
      Second, two HR-correction approaches were proposed: one based on regression
      formulas and another one based on interpolating RR time series. Finally, standard
      and HR-corrected HRV indices were studied in a body position change database. The
      simulation study showed the HR-dependence of non-linear indices as a sampling
      rate effect, as well as the ability of the proposed HR-corrections to attenuate
      mean HR influence. Analysis in a body position changes database shows that
      correlation dimension was reduced around 21% in median values in standing with
      respect to supine position (p < 0.05), concomitant with a 28% increase in mean HR
      (p < 0.05). After HR-correction, correlation dimension decreased around 18% in
      standing with respect to supine position, being the decrease still significant.
      Sample and approximate entropy showed similar trends. HR-corrected nonlinear HRV
      indices could represent an improvement in their applicability as markers of ANS
      modulation when mean HR changes.

PMID- 27895589
TI  - Amino Acid Changes at Arginine 204 of Troponin I Result in Increased Calcium
      Sensitivity of Force Development.
AB  - Mutations in human cardiac troponin I (cTnI) have been associated with
      restrictive, dilated, and hypertrophic cardiomyopathies. The most commonly
      occurring residue on cTnI associated with familial hypertrophic cardiomyopathy
      (FHC) is arginine (R), which is also the most common residue at which multiple
      mutations occur. Two FHC mutations are known to occur at cTnI arginine 204, R204C
      and R204H, and both are associated with poor clinical prognosis. The R204H
      mutation has also been associated with restrictive cardiomyopathy (RCM). To
      characterize the effects of different mutations at the same residue (R204) on the
      physiological function of cTnI, six mutations at R204 (C, G, H, P, Q, W) were
      investigated in skinned fiber studies. Skinned fiber studies showed that all
      tested mutations at R204 caused significant increases in Ca2+ sensitivity of
      force development (DeltapCa50 = 0.22-0.35) when compared to wild-type (WT) cTnI.
      Investigation of the interactions between the cTnI mutants and WT cardiac
      troponin C (cTnC) or WT cardiac troponin T (cTnT) showed that all the mutations
      investigated, except R204G, affected either or both cTnI:cTnT and cTnI:cTnC
      interactions. The R204H mutation affected both cTnI:cTnT and cTnI:cTnC
      interactions while the R204C mutation affected only the cTnI:cTnC interaction.
      These results suggest that different mutations at the same site on cTnI could
      have varying effects on thin filament interactions. A mutation in fast skeletal
      TnI (R174Q, homologous to cTnI R204Q) also significantly increased Ca2+
      sensitivity of force development (DeltapCa50 = 0.16). Our studies indicate that
      known cTnI mutations associated with poor prognosis (R204C and R204H) exhibit
      large increases in Ca2+ sensitivity of force development. Therefore, other R204
      mutations that cause similar increases in Ca2+ sensitivity are also likely to
      have poor prognoses.

PMID- 27895587
TI  - Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut
      Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal
      Models.
AB  - Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non
      alcoholic fatty liver diseases (NAFLD), is associated with vitamin D
      insufficiency/deficiency in epidemiological studies, while the underlying
      mechanism is poorly addressed. On the other hand, disorder of gut microbiota,
      namely dysbiosis, is known to cause MetS and NAFLD. It is also known that
      systemic inflammation blocks insulin signaling pathways, leading to insulin
      resistance and glucose intolerance, which are the driving force for hepatic
      steatosis. Vitamin D receptor (VDR) is highly expressed in the ileum of the small
      intestine, which prompted us to test a hypothesis that vitamin D signaling may
      determine the enterotype of gut microbiota through regulating the intestinal
      interface. Here, we demonstrate that high-fat-diet feeding (HFD) is necessary but
      not sufficient, while additional vitamin D deficiency (VDD) as a second hit is
      needed, to induce robust insulin resistance and fatty liver. Under the two hits
      (HFD+VDD), the Paneth cell-specific alpha-defensins including alpha-defensin 5
      (DEFA5), MMP7 which activates the pro-defensins, as well as tight junction genes,
      and MUC2 are all suppressed in the ileum, resulting in mucosal collapse,
      increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which
      underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D
      deficient high fat feeding (HFD+VDD), Helicobacter hepaticus, a known murine
      hepatic-pathogen, is substantially amplified in the ileum, while Akkermansia
      muciniphila, a beneficial symbiotic, is diminished. Likewise, the VD receptor
      (VDR) knockout mice exhibit similar phenotypes, showing down regulation of alpha
      defensins and MMP7 in the ileum, increased Helicobacter hepaticus and suppressed
      Akkermansia muciniphila. Remarkably, oral administration of DEFA5 restored
      eubiosys, showing suppression of Helicobacter hepaticus and increase of
      Akkermansia muciniphila in association with resolving metabolic disorders and
      fatty liver in the HFD+VDD mice. An in vitro analysis showed that DEFA5 peptide
      could directly suppress Helicobacter hepaticus. Thus, the results of this study
      reveal critical roles of a vitamin D/VDR axis in optimal expression of defensins
      and tight junction genes in support of intestinal integrity and eubiosis to
      suppress NAFLD and metabolic disorders.

PMID- 27895591
TI  - Comparison in Conscious Rabbits of the Baroreceptor-Heart Rate Reflex Effects of
      Chronic Treatment with Rilmenidine, Moxonidine, and Clonidine.
AB  - We investigated the effects of chronic subcutaneous treatment with centrally
      acting antihypertensive agents moxonidine, rilmenidine, and clonidine on the
      baroreflex control of heart rate (HR) in conscious normotensive rabbits over 3
      weeks. Infusions of phenylephrine and nitroprusside were performed at week 0 and
      at weeks 1 and 3 of treatment to determine mean arterial pressure (MAP)-HR
      baroreflex relationships. A second curve was performed after intravenous
      methscopolamine to determine the sympathetic baroreflex relationship. The vagal
      component of the reflex was determined by subtracting the sympathetic curve from
      the intact curve. Clonidine and moxonidine (both 1 mg/kg/day), and rilmenidine (5
      mg/kg/day), reduced MAP by 13 +/- 3, 15 +/- 2, and 13 +/- 2 mmHg, respectively,
      but had no effect on HR over the 3-week treatment period. Whilst all three
      antihypertensive agents shifted baroreflex curves to the left, parallel to the
      degree of hypotension, moxonidine and rilmenidine decreased the vagal
      contribution to the baroreflex by decreasing the HR range of the reflex but
      moxonidine also increased sympathetic baroreflex range and sensitivity. By
      contrast clonidine had little chronic effect on the cardiac baroreflex. The
      present study shows that second generation agents moxonidine and rilmenidine but
      not first generation agent clonidine chronically shift the balance of baroreflex
      control of HR toward greater sympathetic and lesser vagal influences. These
      changes if translated to hypertensive subjects, may not be particularly helpful
      in view of the already reduced vagal contribution in hypertension.

PMID- 27895590
TI  - Brain Functional Connectivity Is Different during Voluntary Concentric and
      Eccentric Muscle Contraction.
AB  - Previous studies report greater activation in the cortical motor network in
      controlling eccentric contraction (EC) than concentric contraction (CC) of human
      skeletal muscles despite lower activation level of the muscle associated with EC.
      It is unknown, however, whether the strength of functional coupling between the
      primary motor cortex (M1) and other involved areas in the brain differs as
      voluntary movements are controlled by a network of regions in the primary,
      secondary and association cortices. Examining fMRI-based functional connectivity
      (FC) offers an opportunity to measure strength of such coupling. To address the
      question, we examined functional MRI (fMRI) data acquired during EC and CC (20
      contractions each with similar movement distance and speed) of the right first
      dorsal interosseous (FDI) muscle in 11 young (20-32 years) and healthy
      individuals and estimated FC between the M1 and a number of cortical regions in
      the motor control network. The major findings from the mechanical and fMRI-based
      FC analysis were that (1) no significant differences were seen in movement
      distance, speed and stability between the EC and CC; (2) significantly stronger
      mean FC was found for CC than EC. Our finding provides novel insights for a
      better understanding of the control mechanisms underlying voluntary movements
      produced by EC and CC. The finding is potentially helpful for guiding the
      development of targeted sport training and/or therapeutic programs for
      performance enhancement and injury prevention.

PMID- 27895592
TI  - Effects of Six Months Training on Physical Capacity and Metaboreflex Activity in
      Patients with Multiple Sclerosis.
AB  - Patients with multiple sclerosis (MS) have an increased systemic vascular
      resistance (SVR) response during the metaboreflex. It has been hypothesized that
      this is the consequence of a sedentary lifestyle secondary to MS. The purpose of
      this study was to discover whether a 6-month training program could reverse this
      hemodynamic dysregulation. Patients were randomly assigned to one of the
      following two groups: the intervention group (MSIT, n = 11), who followed an
      adapted training program; and the control group (MSCTL, n = 10), who continued
      with their sedentary lifestyle. Cardiovascular response during the metaboreflex
      was evaluated using the post-exercise muscle ischemia (PEMI) method and during a
      control exercise recovery (CER) test. The difference in hemodynamic variables
      such as stroke volume (SV), cardiac output (CO), and SVR between the PEMI and the
      CER tests was calculated to assess the metaboreflex response. Moreover, physical
      capacity was measured during a cardiopulmonary test till exhaustion. All tests
      were repeated after 3 and 6 months (T3 and T6, respectively) from the beginning
      of the study. The main result was that the MSIT group substantially improved
      parameters related to physical capacity (+5.31 +/- 5.12 ml.min-1/kg in maximal
      oxygen uptake at T6) in comparison with the MSCTL group (-0.97 +/- 4.89 ml.min
      1/kg at T6; group effect: p = 0.0004). However, none of the hemodynamic variables
      changed in response to the metaboreflex activation. It was concluded that a 6
      month period of adapted physical training was unable to reverse the hemodynamic
      dys-regulation in response to metaboreflex activation in these patients.

PMID- 27895593
TI  - Baseline Muscle Mass Is a Poor Predictor of Functional Overload-Induced Gain in
      the Mouse Model.
AB  - Genetic background contributes substantially to individual variability in muscle
      mass. Muscle hypertrophy in response to resistance training can also vary
      extensively. However, it is less clear if muscle mass at baseline is predictive
      of the hypertrophic response. The aim of this study was to examine the effect of
      genetic background on variability in muscle mass at baseline and in the adaptive
      response of the mouse fast- and slow-twitch muscles to overload. Males of eight
      laboratory mouse strains: C57BL/6J (B6, n = 17), BALB/cByJ (n = 7), DBA/2J (D2, n
      = 12), B6.A-(rs3676616-D10Utsw1)/Kjn (B6.A, n = 9), C57BL/6J-Chr10A/J/NaJ
      (B6.A10, n = 8), BEH+/+ (n = 11), BEH (n = 12), and DUHi (n = 12), were studied.
      Compensatory growth of soleus and plantaris muscles was triggered by a 4-week
      overload induced by synergist unilateral ablation. Muscle weight in the control
      leg (baseline) varied from 5.2 +/- 07 mg soleus and 11.4 +/- 1.3 mg plantaris in
      D2 mice to 18.0 +/- 1.7 mg soleus in DUHi and 43.7 +/- 2.6 mg plantaris in BEH (p
      < 0.001 for both muscles). In addition, soleus in the B6.A10 strain was ~40%
      larger (p < 0.001) compared to the B6. Functional overload increased muscle
      weight, however, the extent of gain was strain-dependent for both soleus (p <
      0.01) and plantaris (p < 0.02) even after accounting for the baseline
      differences. For the soleus muscle, the BEH strain emerged as the least
      responsive, with a 1.3-fold increase, compared to a 1.7-fold gain in the most
      responsive D2 strain, and there was no difference in the gain between the B6.A10
      and B6 strains. The BEH strain appeared the least responsive in the gain of
      plantaris as well, 1.3-fold, compared to ~1.5-fold gain in the remaining strains.
      We conclude that variation in muscle mass at baseline is not a reliable predictor
      of that in the overload-induced gain. This suggests that a different set of genes
      influence variability in muscle mass acquired in the process of normal
      development, growth, and maintenance, and in the process of adaptive growth of
      the muscle challenged by overload.

PMID- 27895594
TI  - Larval Exposure to Chlorpyrifos Affects Nutritional Physiology and Induces
      Genotoxicity in Silkworm Philosamia ricini (Lepidoptera: Saturniidae).
AB  - Chlorpyrifos is a most widely used organophosphate insecticide because of its
      cost effectiveness and degradable nature. However, this pesticide enters and
      contaminates the environment either by direct application, spray drifts or crop
      run off and shows adverse effect on the non-targeted organisms. Philosamia ricini
      (eri silkworm), one of the most exploited, domesticated and commercialized non
      mulberry silkworm is known for mass production of eri silk. The silkworm larvae
      get exposed to pesticide residues on the leaves of food plants. The present study
      investigates the effect of commercial formulation of chlorpyrifos (Pyrifos-20 EC)
      on eri silkworm. Initially the LC50 value of chlorpyrifos was determined at 24-96
      h and further experiments were carried out with sub lethal concentrations of the
      chlorpyrifos after 24 h of exposure period. The potential toxicity of
      chlorpyrifos was evaluated as a fuction of metabolism and nutritional physiology
      in 3rd, 4th, and 5th instar larvae. Alteration in histoarchitecture of 5th instar
      eri silkworm gut exposed to sub lethal concentration of chlorpyrifos formulation
      was also studied. Chlorpyrifos induced genotoxicity in silkworm hemocytes was
      also investigated by single cell gel electrophoresis, micronuclei assay, and
      apoptosis assay. Herein, LC50 values of chlorpyrifos were calculated as 3.83,
      3.35, 2.68, and 2.35 mg/L at 24, 48, 72, and 96h respectively. A significant
      decrease in trehalose activity along with digestive enzyme activity was observed
      in chlorpyrifos affected groups (P < 0.05). Further, genotoxicity study revealed
      higher tail percentage, tail length and tail moment of the damage DNA in
      chlorpyrifos exposed groups (P < 0.001). Moreover, at 2.0 mg/L concentration, ~10
      fold increases in tail length was observed as compared to the control. Results
      showed activation of caspase activity following 24 h chlorpyrifos exposure (1.5
      and 2.0 mg/L) in a dose-dependent manner. Moreover, in control group less number
      of apoptotic cells was detected, however in both chlorpyrifos exposed groups'
      numbers of apoptotic cells were statistically higher (P < 0.001). Taken together,
      this study provides evidence that chlorpyrifos pollution might have adverse
      effect on overall nutritional physiology and genotoxicity of eri silkworm that
      could lead to reduced survivability of this economically beneficial insect.

PMID- 27895596
TI  - Reciprocal Modulation of IK1-INa Extends Excitability in Cardiac Ventricular
      Cells.
AB  - The inwardly rectifying potassium current (IK1) and the fast inward sodium
      current (INa) are reciprocally modulated in mammalian ventricular myocytes. An
      increase in the expression of channels responsible for one of these two currents
      results in a corresponding increase in expression of the other. These currents
      are critical in the propagation of action potentials (AP) during the normal
      functioning of the heart. This study identifies a physiological role for IK1-INa
      reciprocal modulation in ventricular fiber activation thresholds and conduction.
      Simulations of action potentials in single cells and propagating APs in cardiac
      fibers were carried out using an existing model of electrical activity in cardiac
      ventricular myocytes. The conductances, GK1, of the inwardly rectifying potassium
      current, and GNa, of the fast inward sodium current were modified independently
      and in tandem to simulate reciprocal modulation. In single cells, independent
      modulation of GK1 alone resulted in changes in activation thresholds that were
      qualitatively similar to those for reciprocal GK1-GNa modulation and unlike those
      due to independent modulation of GNa alone, indicating that GK1 determines the
      cellular activation threshold. On the other hand, the variations in conduction
      velocity in cardiac cell fibers were similar for independent GNa modulation and
      for tandem changes in GK1-GNa, suggesting that GNa is primarily responsible for
      setting tissue AP conduction velocity. Conduction velocity dependence on GK1-GNa
      is significantly affected by the intercellular gap junction conductance. While
      the effects on the passive fiber space constant due to changes in both GK1 and
      the intercellular gap junction conductance, Ggj, were in line with linear cable
      theory predictions, both conductances had surprisingly large effects on fiber
      activation thresholds. Independent modulation of GK1 rendered cardiac fibers
      inexcitable at higher levels of GK1 whereas tandem GK1-GNa changes allowed fibers
      to remain excitable at high GK1 values. Reciprocal modulation of the inwardly
      rectifying potassium current and the fast inward sodium current may have a
      functional role in allowing cardiac tissue to remain excitable when IK1 is
      upregulated.

PMID- 27895595
TI  - Moving from Histopathology to Molecular Tools in the Diagnosis of Molluscs
      Diseases of Concern under EU Legislation.
AB  - One of the main factors limiting molluscs production is the presence of pathogens
      and diseases. Disease agent transfer via transfers of live molluscs has been a
      major cause of disease outbreaks and epizootics. Because of that, the European
      Union has adopted several decisions and directives, the last in 2006 (2006/88/EC)
      to control movements of marine organisms over the European countries. Once the
      disease is established in a determined area its eradication is a complicated task
      because life cycle of pathogens are not completely known and only a good and
      early diagnosis of the disease could be the most appropriate way to deal with it.
      Besides, molluscs do not have an adaptive immune response and vaccination
      strategies are not possible. Molluscs listed diseases under EU legislation are
      mainly protozoan parasites, that's why histological techniques are recognized for
      their diagnosis. However, molecular techniques are being increasingly used
      primarily as confirmatory techniques of the presence of the pathogens but also in
      disease monitoring programs. Research perspectives are mainly focussed in the
      optimization, of the already described techniques to gain in sensitivity and
      sensibility and in the development of new molecular biology techniques
      (quantitative real time PCRs), that are faster and easier to apply and that allow
      a positive diagnosis even in early stages of infection. However, molecular tools
      detect DNA sequences of the pathogen which does not imply that pathogen is viable
      in the cell host and the infection is established. Consequently, it needs to be
      validated against other techniques, such as histology or in situ hybridization,
      so that its reliability can be determined.

PMID- 27895597
TI  - Corrigendum: Pacemaking Property of RVLM Presympathetic Neurons.
AB  - [This corrects the article on p. 424 in vol. 7, PMID: 27713705.].

PMID- 27895598
TI  - Pharmacotherapy for Alcohol Use Disorders: Physicians' Perceptions and Practices.
AB  - BACKGROUND AND OBJECTIVES: Alcohol use disorders (AUDs) are an important cause of
      morbidity and mortality. Despite the National Institute on Alcohol Abuse and
      Alcoholism (NIAAA) recommendations that medications be considered for patients
      with alcohol dependence, the mainstay of treatment has been counseling. We
      designed a survey to assess the treatment practices of psychiatrists and family
      medicine (FM) physicians in an effort to identify barriers to the use of
      pharmacotherapy and develop strategies to increase physician knowledge and
      utilization of these medications. METHODS: An anonymous online survey was sent to
      FM physicians and psychiatrists nationwide. The survey collected demographic
      information and assessed prescription of medications in treating AUDs, including
      FDA-approved medications and other medications used off-label for this purpose.
      We also examined factors that would lead to an increase in AUDs pharmacotherapy.
      RESULTS: A total of 491 surveys were completed, with 475 responses included in
      the final analyses. 45.5% of participants were psychiatrists vs. 54.5% FM
      physicians. The 74.7% respondents had used medications to treat AUDs, with
      psychiatrists more likely to have prescribed acamprosate, naltrexone, and several
      off-label medications. FM physicians were more likely to report efficacy
      concerns. A majority of all physicians sampled would increase pharmacotherapy of
      AUDs with increased training. DISCUSSION: In our sample, most physicians have
      used medications to treat AUDs. There were concerns about efficacy with all non
      FDA-approved medications, but limited treatment success even with FDA-approved
      medications. Greater education about pharmacotherapy, including predictors for
      treatment response amongst patients, should help alleviate some of the
      uncertainties reported with medications' efficacy and lead to a more
      individualized treatment approach.

PMID- 27895600
TI  - The Implementation of Bring Your Own Device (BYOD) in Primary [Elementary]
      Schools.

PMID- 27895599
TI  - Task Inhibition and Response Inhibition in Older vs. Younger Adults: A Diffusion
      Model Analysis.
AB  - Differences in inhibitory ability between older (64-79 years, N = 24) and younger
      adults (18-26 years, N = 24) were investigated using a diffusion model analysis.
      Participants performed a task-switching paradigm that allows assessing n-2 task
      repetition costs, reflecting inhibitory control on the level of tasks, as well as
      n-1 response-repetition costs, reflecting inhibitory control on the level of
      responses. N-2 task repetition costs were of similar size in both age groups.
      Diffusion model analysis revealed that for both younger and older adults, drift
      rate parameters were smaller in the inhibition condition relative to the control
      condition, consistent with the idea that persisting task inhibition slows down
      response selection. Moreover, there was preliminary evidence for task inhibition
      effects in threshold separation and non-decision time in the older, but not the
      younger adults, suggesting that older adults might apply different strategies
      when dealing with persisting task inhibition. N-1 response-repetition costs in
      mean RT were larger in older than younger adults, but in mean error rates tended
      to be larger in younger than older adults. Diffusion-model analysis revealed
      longer non-decision times in response repetitions than response switches in both
      age groups, consistent with the idea that motor processes take longer in response
      repetitions than response switches due to persisting response inhibition of a
      previously executed response. The data also revealed age-related differences in
      overall performance: Older adults responded more slowly and more accurately than
      young adults, which was reflected by a higher threshold separation parameter in
      diffusion model analysis. Moreover, older adults showed larger non-decision times
      and higher variability in non-decision time than young adults, possibly
      reflecting slower and more variable motor processes. In contrast, overall drift
      rate did not differ between older and younger adults. Taken together, diffusion
      model analysis revealed differences in overall performance between the age
      groups, as well as preliminary evidence for age differences in dealing with task
      inhibition, but no evidence for an inhibitory deficit in older age.

PMID- 27895601
TI  - The Role of Psychological Capital and Intragroup Conflict on Employees' Burnout
      and Quality of Service: A Multilevel Approach.
AB  - Previous studies have found a negative association between intragroup conflict
      and both employees' health and performance, including the quality of service that
      employees provide. However, some authors have indicated that such negative
      effects of intragroup conflict depend on how conflict is managed. In addition, at
      individual level, research is increasingly emphasizing the role of psychological
      strengths (i.e., psychological capital) as predictors of health and performance.
      Thus, this research addresses both a main effect at individual level
      (psychological capital on burnout/quality of service) and a moderated cross-level
      model (2-2-1: intragroup conflict, conflict management climate and
      burnout/quality of service) in a cross-sectional survey study (N = 798 workers
      nested in 55 units/facilities). Results revealed a main effect of psychological
      capital on both burnout (r = -0.50) and quality of service (r = 0.28). Also,
      there was an association between intragroup relationship conflict and burnout (r
      = 0.33). Finally, there was an interaction effect in which conflict management
      climate buffers the negative association between intragroup conflict and quality
      of service. Practical implications of these results for developing positive and
      healthy organizations that prevent potential psychosocial risks at group level
      while promote individual strengths are discussed.

PMID- 27895603
TI  - Neighborhood Deprivation Negatively Impacts Children's Prosocial Behavior.
AB  - Children show stronger cooperative behavior in experimental settings as they get
      older, but little is known about how the environment of a child shapes this
      development. In adults, prosocial behavior toward strangers is markedly decreased
      in low socio-economic status (SES) neighborhoods, suggesting that environmental
      harshness has a negative impact on some prosocial behaviors. Similar results have
      been obtained with 9-year-olds recruited from low vs. high SES schools. In the
      current study, we investigate whether these findings generalize to a younger age
      group and a developing country. Specifically, we worked with a sample of thirty
      nine 6- to 7-year-olds in two neighborhoods in a single city in Romania. Using a
      "Quality Dictator Game" that offers greater resolution than previous measures, we
      find that children living in the harsher neighborhood behave less prosocially
      toward a stranger than children living in the less harsh neighborhood.

PMID- 27895602
TI  - Motivational and Behavioral Activation as an Adjunct to Psychiatric
      Rehabilitation for Mild to Moderate Negative Symptoms in Individuals with
      Schizophrenia: A Proof-of-Concept Pilot Study.
AB  - Few psychosocial approaches address the negative symptoms of schizophrenia, which
      shares common features with depression and anxiety. Behavioral activation (BA) is
      effective for addressing depression and anxiety in adults with various mental
      disorders. Motivational interviewing (MI) has been successfully applied to
      address ambivalence or lack of motivation toward treatment. Motivational and
      behavioral activation (mBA) has been developed by incorporating the core
      principles from BA and MI with recent findings on the negative symptoms of
      schizophrenia. In this study, we aimed to examine the feasibility and preliminary
      efficacy of mBA in a non-randomized controlled pilot study that included
      individuals with schizophrenia with mild to moderate negative symptoms receiving
      psychiatric rehabilitation. A total of 73 individuals with schizophrenia were
      recruited. Forty-seven of the participants who met the study inclusion and
      exclusion criteria were assigned to either an mBA + usual psychiatric
      rehabilitation group (mBA) or a usual psychiatric rehabilitation only group
      (treatment as usual, TAU). Administering mBA to individuals with schizophrenia
      with mild to moderate negative symptoms was feasible in a community mental health
      setting. Relative to TAU, mBA was associated with large effects in reducing
      negative symptoms measured using the Positive and Negative Syndrome Scale (PANSS)
      and the Brief Negative Symptom Scale (BNSS). However, after considering PANSS
      cognitive deficits and marital status as covariates due to significant
      differences in their baseline levels, the treatment effects on the BNSS were
      partially observed. In addition, participants in the mBA group showed improved
      verbal learning and memory compared with those in the TAU group. In individuals
      with schizophrenia receiving the usual forms of psychiatric rehabilitation in a
      community mental health setting, mBA appears to offer a promising adjunctive
      approach for addressing mild to moderate negative symptoms. Further
      investigations are needed to replicate the current findings in a randomized
      controlled trial.

PMID- 27895604
TI  - Virtue Existential Career Model: A Dialectic and Integrative Approach Echoing
      Eastern Philosophy.
AB  - Our Virtue Existential Career (VEC) model aims at complementing western modernism
      and postmodernism career theories with eastern philosophy. With dialectical
      philosophy and virtue-practice derived from the Classic of Changes, the VEC
      theoretical foundation incorporates merits from Holland typology, Minnesota
      Theory of Work Adjustment, Social Cognitive Career Theory, Meaning Therapy,
      Narrative Approach Career Counseling, and Happenstance Learning Theory. While
      modernism considers a matched job as an ideal career vision and prefers rational
      strategies (controlling and realizing) to achieve job security; postmodernism
      prefers appreciating and adapting strategies toward openness and appreciates
      multiple possible selves and occupations, our model pursues a blending of
      security and openness via controlling-and-realizing and appreciating-and-adapting
      interwoven with each other in a dialectical and harmonious way. Our VEC
      counseling prototype aims at a secular goal of living on the earth with ways and
      harmony () and an ultimate end to spiral up to the wisdom of living up to the way
      of heaven () with mind and virtue (). A VEC counseling process of five major
      career strategies, metaphorical stories of qian and kun, and experiential
      activities are developed to deliver VEC concepts. The VEC model and prototype
      presented in this research is the product of an action research following Lewin's
      (1946) top-to-down model. Situated structure analyses were conducted to further
      investigate the adequacy of this version of VEC model and prototype. Data from
      two groups (one for stranded college graduates and the other for growing college
      students) revealed empirical supports. Yang type of career praxes tends to induce
      actualization, which resulting in realistic goals and concrete action plans; yin
      type of career praxes tends to increase self-efficacy, which resulting in
      positive attitude toward current situatedness and future development. Acceptance
      and dialectic thinking often result from yin-yang-blending career praxes. Growing
      developers benefit from a strategy sequence of yang-yin-synthesized; stranded
      developers from a strategy sequence of yin-yang-synthesized. Our contributions
      and limitations are discussed in the context of developing indigenous career
      theories and practices for a globalized and ever-changing world.

PMID- 27895605
TI  - Social Cognition in Preschoolers: Effects of Early Experience and Individual
      Differences.
AB  - Social cognition is the way in which people process, remember, and use
      information in social contexts to explain and predict their own behavior and that
      of others. Children's social cognition may be influenced by multiple factors,
      both external and internal to the child. In the current study, two aspects of
      social cognition were examined: Theory of Mind and Emotion Understanding. The aim
      of this study was to analyze the effects of type of early care (0-3 years of
      age), maternal education, parents' country of birth, and child's language on the
      social cognition of 118 Italian preschoolers. To our knowledge, the joint effect
      of these variables on social cognition has not previously been investigated in
      the literature. The measures used to collect social cognition and linguistic data
      were not parent- or teacher-reports, but based on direct assessment of the
      children through two standardized tests, the Test of Emotion Comprehension and
      the ToM Storybooks. Relationships among the variables showed a complex pattern.
      Overall, maternal education and linguistic competence showed a systematic effect
      on social cognition; the linguistic competence mediated the effect of maternal
      education. In children who had experienced centre-base care in the first 3 years
      of life, the effect of maternal education disappeared, supporting the protective
      role of centre-base care for children with less educated mothers. The children
      with native and foreign parents did not significantly differ on the social
      cognition tasks. Limits of the study, possible educational outcomes and future
      research lines were discussed.

PMID- 27895607
TI  - Caffeine Enhances Memory Performance in Young Adults during Their Non-optimal
      Time of Day.
AB  - Many college students struggle to perform well on exams in the early morning.
      Although students drink caffeinated beverages to feel more awake, it is unclear
      whether these actually improve performance. After consuming coffee (caffeinated
      or decaffeinated), college-age adults completed implicit and explicit memory
      tasks in the early morning and late afternoon (Experiment 1). During the morning,
      participants ingesting caffeine demonstrated a striking improvement in explicit
      memory, but not implicit memory. Caffeine did not alter memory performance in the
      afternoon. In Experiment 2, participants engaged in cardiovascular exercise in
      order to examine whether increases in physiological arousal similarly improved
      memory. Despite clear increases in physiological arousal, exercise did not
      improve memory performance compared to a stretching control condition. These
      results suggest that caffeine has a specific benefit for memory during students'
      non-optimal time of day - early morning. These findings have real-world
      implications for students taking morning exams.

PMID- 27895606
TI  - Being in a Romantic Relationship Is Associated with Reduced Gray Matter Density
      in Striatum and Increased Subjective Happiness.
AB  - Romantic relationship, a widespread feature of human society, is one of the most
      influential factors in daily life. Although stimuli related to romantic love or
      being in a romantic relationship commonly result in enhancement of activation or
      functional connectivity of the reward system, including the striatum, the
      structure underlying romantic relationship-related regions remain unclear.
      Because individual experiences can alter gray matter within the adult human
      brain, we hypothesized that romantic relationship is associated with structural
      differences in the striatum related to the positive subjective experience of
      being in a romantic relationship. Because intimate romantic relationships
      contribute to perceived subjective happiness, this subjective enhancement of
      happiness might be accompanied by the experience of positive events related to
      being in a romantic relationship. To test this hypothesis and elucidate the
      structure involved, we compared subjective happiness, an indirect measure of the
      existence of positive experiences caused by being in a romantic relationship, of
      participants with or without romantic partners (N = 68). Furthermore, we also
      conducted a voxel-based morphometry study of the effects of being in a romantic
      relationship (N = 113). Being in a romantic relationship was associated with
      greater subjective happiness and reduced gray matter density within the right
      dorsal striatum. These results suggest that being in a romantic relationship
      enhances perceived subjective happiness via positive experiences. Furthermore,
      the observed reduction in gray matter density in the right dorsal striatum may
      reflect an increase in saliency of social reward within a romantic relationship.
      Thus, being in a romantic relationship is associated with positive experiences
      and a reduction of gray matter density in the right dorsal striatum, representing
      a modulation of social reward.

PMID- 27895609
TI  - To Fake or Not to Fake: Antecedents to Interview Faking, Warning Instructions,
      and Its Impact on Applicant Reactions.
AB  - In the present study, we examined the antecedents and processes that impact job
      interviewees' decisions to engage in deceptive impression management (i.e.,
      interview faking). Willingness and capacity to engage in faking were found to be
      the processes underlying the decision to use deceptive impression management in
      the interview. We also examined a personality antecedent to this behavior,
      Honesty-Humility, which was negatively related to the use of deceptive impression
      management through increased willingness to engage in these behaviors. We also
      tested a possible intervention to reduce IM. In particular, we found that
      warnings against faking - specifically, an identification warning - reduced both
      the perceived capacity to engage in interview faking, and subsequent use of
      several faking behaviors. Moreover, this warning reduced faking without adversely
      impacting applicant reactions.

PMID- 27895610
TI  - The Origin of Social Evaluation, Social Eavesdropping, Reputation Formation,
      Image Scoring or What You Will.
AB  - Social evaluation is a mental process that leverages the preference toward
      prosocial partners (positivity bias) against the avoidance of antisocial
      individuals (negativity bias) in a cooperative context. The phenomenon is well
      known in humans, and recently comparative investigations looked at the possible
      evolutionary origins. So far social evaluation has been investigated mainly in
      non-human and human primates and dogs, however, there are few data on the
      presence of negativity/positivity bias in client-cleaner reef fish interactions
      as well. Unfortunately, the comparative approach to social evaluation is hindered
      by conceptual and procedural differences in experimental studies. By reviewing
      current knowledge on social evaluation in different species, we aim to point out
      that the capacity for social evaluation is not restricted to humans alone;
      however, its building blocks (negativity and positivity bias) may be more
      widespread separately. Due to its importance in survival, negativity bias likely
      to be widespread among animals; however, there has been less intensive selective
      pressure for the identification of prosocial companions, thus the latter ability
      may have emerged only in certain social species. We present a general framework
      and argue that negativity and positivity bias evolve independently and can be
      considered as social evaluation only if a unified behavior and cognitive system
      deals with both biases in concert.

PMID- 27895611
TI  - Instructional Changes Adopted for an Engineering Course: Cluster Analysis on
      Academic Failure.
AB  - As first year students come from diverse backgrounds, basic skills should be
      accessible to everyone as soon as possible. Transferring such skills to these
      students is challenging, especially in highly technical courses. Ensuring that
      essential knowledge is acquired quickly promotes the student's self-esteem and
      may positively influence failure rates. Metaphors can help do this. Metaphors are
      used to understand the unknown. This paper shows how we made a turn in student
      learning at the University of Almeria. Our hypothesis assumed that metaphors
      accelerate the acquisition of basic knowledge so that other skills built on that
      foundation are easily learned. With these goals in mind, we changed the way we
      teach by using metaphors and abstract concepts in a computer organization course,
      a technical course in the first year of an information technology engineering
      degree. Cluster analysis of the data on collective student performance after this
      methodological change clearly identified two distinct groups. These two groups
      perfectly matched the "before and after" scenarios of the use of metaphors. The
      study was conducted during 11 academic years (2002/2003 to 2012/2013). The 475
      observations made during this period illustrate the usefulness of this change in
      teaching and learning, shifting from a propositional teaching/learning model to a
      more dynamic model based on metaphors and abstractions. Data covering the whole
      period showed favorable evolution of student achievement and reduced failure
      rates, not only in this course, but also in many of the following more advanced
      courses. The paper is structured in five sections. The first gives an
      introduction, the second describes the methodology. The third section describes
      the sample and the study carried out. The fourth section presents the results
      and, finally, the fifth section discusses the main conclusions.

PMID- 27895608
TI  - Genetic Consideration of Schizotypal Traits: A Review.
AB  - Schizotypal traits are of interest and importance in their own right and also
      have theoretical and clinical associations with schizophrenia. These traits
      comprise attenuated psychotic symptoms, social withdrawal, reduced cognitive
      capacity, and affective dysregulation. The link between schizotypal traits and
      psychotic disorders has long since been debated. The status of knowledge at this
      point is such schizotypal traits are a risk for psychotic disorders, but in and
      of themselves only confer liability, with other risk factors needing to be
      present before a transition to psychosis occurs. Investigation of schizotypal
      traits also has the possibility to inform clinical and research pursuits
      concerning those who do not make a transition to psychotic disorders. A growing
      body of literature has investigated the genetic underpinnings of schizotypal
      traits. Here, we review association, family studies and describe genetic
      disorders where the expression of schizotypal traits has been investigated. We
      conducted a thorough review of the existing literature, with multiple search
      engines, references, and linked articles being searched for relevance to the
      current review. All articles and book chapters in English were sourced and
      reviewed for inclusion. Family studies demonstrate that schizotypal traits are
      elevated with increasing genetic proximity to schizophrenia and some chromosomal
      regions have been associated with schizotypy. Genes associated with schizophrenia
      have provided the initial start point for the investigation of candidate genes
      for schizotypal traits; neurobiological pathways of significance have guided
      selection of genes of interest. Given the chromosomal regions associated with
      schizophrenia, some genetic disorders have also considered the expression of
      schizotypal traits. Genetic disorders considered all comprise a profile of
      cognitive deficits and over representation of psychotic disorders compared to the
      general population. We conclude that genetic variations associated with
      schizotypal traits require further investigation, perhaps with targeted
      phenotypes narrowed to assist in refining the clinical end point of significance.

PMID- 27895613
TI  - Editorial: Beyond Reward: Insights from Love and Addiction.

PMID- 27895612
TI  - Forgiveness from Emotion Fit: Emotional Frame, Consumer Emotion, and Feeling
      Right in Consumer Decision to Forgive.
AB  - Three studies examine an emotion fit effect in the crisis communication, namely,
      the interaction between emotional frames of guilt and shame and consumer emotions
      of anger and fear on consumer forgiveness. Guilt-framing communication results in
      higher forgiveness than shame-framing for angry consumers, whereas shame-framing
      communication results in higher forgiveness than guilt-framing for fearful
      consumers. These effects are driven by consumers' accessible regulatory foci
      associated with anger/fear and guilt/shame. Specifically, feelings of anger
      activate a promotion focus that is represented by guilt frames, while feelings of
      fear activate a prevention focus that is enacted by shame frames. Compared with
      emotion non-fit (i.e., anger to shame and fear to guilt), emotion fit (i.e.,
      anger to guilt and fear to shame) facilitates greater feeling-right and consumer
      forgiveness. The findings offer novel insights for extant literature on emotion,
      crisis communication, and regulatory focus theory, as well as practical
      suggestions regarding the emotional frames.

PMID- 27895614
TI  - Mimological Reveries? Disconfirming the Hypothesis of Phono-Emotional Iconicity
      in Poetry.
AB  - The present study retested previously reported empirical evidence suggesting an
      iconic relation between sound and emotional meaning in poetry. To this end, we
      analyzed the frequency of certain phoneme classes in 48 German poems and
      correlated them with ratings for emotional classification. Our analyses provide
      evidence for a link between the emotional classification of poems (joyful vs.
      sad) and the perception of tonal contrast as reflected in the attribution of
      phenomenological sound qualia (bright vs. dark). However, we could not confirm
      any of the previous hypotheses and findings regarding either a connection between
      the frequencies of occurrence of specific vowel classes and the perception of
      tonal contrast, or a relation between the frequencies of occurrence of consonant
      classes and emotional classification.

PMID- 27895615
TI  - The Intersubjective Nature of Play Development and Its Role in Child
      Psychoanalytic Psychotherapy.

PMID- 27895616
TI  - Cognitive Style: Time to Experiment.

PMID- 27895619
TI  - A Functional Magnetic Resonance Imaging Study of Head Movements in Cervical
      Dystonia.
AB  - Cervical dystonia (CD) is a neurological disorder characterized by abnormal
      movements and postures of the head. The brain regions responsible for these
      abnormal movements are not well understood, because most imaging techniques for
      assessing regional brain activity cannot be used when the head is moving.
      Recently, we mapped brain activation in healthy individuals using functional
      magnetic resonance imaging during isometric head rotation, when muscle
      contractions occur without actual head movements. In the current study, we used
      the same methods to explore the neural substrates for head movements in subjects
      with CD who had predominantly rotational abnormalities (torticollis). Isometric
      wrist extension was examined for comparison. Electromyography of neck and hand
      muscles ensured compliance with tasks during scanning, and any head motion was
      measured and corrected. Data were analyzed in three steps. First, we conducted
      within-group analyses to examine task-related activation patterns separately in
      subjects with CD and in healthy controls. Next, we directly compared task-related
      activation patterns between participants with CD and controls. Finally,
      considering that the abnormal head movements in CD occur in a consistently
      patterned direction for each individual, we conducted exploratory analyses that
      involved normalizing data according to the direction of rotational CD. The
      between-group comparisons failed to reveal any significant differences, but the
      normalization procedure in subjects with CD revealed that isometric head rotation
      in the direction of dystonic head rotation was associated with more activation in
      the ipsilateral anterior cerebellum, whereas isometric head rotation in the
      opposite direction was associated with more activity in sensorimotor cortex.
      These findings suggest that the cerebellum contributes to abnormal head rotation
      in CD, whereas regions in the cerebral cortex are involved in opposing the
      involuntary movements.

PMID- 27895618
TI  - Cyclooxygenase-1 as a Potential Therapeutic Target for Seizure Suppression:
      Evidences from Zebrafish Pentylenetetrazole-Seizure Model.
AB  - Cyclooxygenases (COX)-1 and -2 are isoenzymes that catalyze the conversion of
      arachidonic acid into prostaglandins (PGs). COX-2 and PGs are rapidly increased
      following seizures and are known to play important roles in the neuroinflammatory
      process. COX-2 isoform has been predominantly explored as the most suitable
      target for pharmacological intervention in epilepsy studies, while COX-1 remains
      poorly investigated. In the present study, we evaluated the effects of selective
      COX-1 inhibitor or selective COX-2 inhibitor on seizure suppression in the
      zebrafish pentylenetetrazole (PTZ)-seizure model. Zebrafish larvae were incubated
      in 5 MUM of SC-236 for 24 h or 2.8 MUM of SC-560 for 30 min, followed by exposure
      to 15 mM PTZ for 60 min. Real-time quantitative PCR analysis was carried out to
      investigate transcription levels of cox1 (ptgs1), as well as to determine cfos
      levels, used as a marker for neuronal activity. Effects of selective COX-2 or COX
      1 inhibitors on locomotor activity response (velocity and distance moved) during
      PTZ exposure were evaluated using the Danio Vision video-tracking system. Our
      results showed an inducible expression of the cox1 gene after 60 min of PTZ
      exposure. Cox1 mRNA levels were upregulated compared with the control group. We
      found that COX-2 inhibition treatment had no effect on zebrafish PTZ-induced
      seizures. On the other hand, COX-1 inhibition significantly attenuated PTZ
      induced increase of locomotor activity and reduced the c-fos mRNA expression.
      These findings suggest that COX-1 inhibition rather than COX-2 has positive
      effects on seizure suppression in the zebrafish PTZ-seizure model.

PMID- 27895617
TI  - Understanding the NG2 Glial Scar after Spinal Cord Injury.
AB  - NG2 cells, also known as oligodendrocyte progenitor cells, are located throughout
      the central nervous system and serve as a pool of progenitors to differentiate
      into oligodendrocytes. In response to spinal cord injury (SCI), NG2 cells
      increase their proliferation and differentiation into remyelinating
      oligodendrocytes. While astrocytes are typically associated with being the major
      cell type in the glial scar, many NG2 cells also accumulate within the glial scar
      but their function remains poorly understood. Similar to astrocytes, these cells
      hypertrophy, upregulate expression of chondroitin sulfate proteoglycans, inhibit
      axon regeneration, contribute to the glial-fibrotic scar border, and some even
      differentiate into astrocytes. Whether NG2 cells also have a role in other
      astrocyte functions, such as preventing the spread of infiltrating leukocytes and
      expression of inflammatory cytokines, is not yet known. Thus, NG2 cells are not
      only important for remyelination after SCI but are also a major component of the
      glial scar with functions that overlap with astrocytes in this region. In this
      review, we describe the signaling pathways important for the proliferation and
      differentiation of NG2 cells, as well as the role of NG2 cells in scar formation
      and tissue repair.

PMID- 27895621
TI  - Immune Modulatory Effects of Human Chorionic Gonadotropin on Dendritic Cells
      Supporting Fetal Survival in Murine Pregnancy.
AB  - Dendritic cells (DCs) are critically involved in the determination of immunity
      vs. tolerance. Hence, DCs are key regulators of immune responses either favoring
      or disfavoring fetal survival. Several factors were proposed to modulate DC
      phenotype and function during pregnancy. Here, we studied whether the pregnancy
      hormone human chorionic gonadotropin (hCG) is involved in DC regulation. In
      vitro, bone marrow-derived DCs (BMDCs) were stimulated in the presence or absence
      of urine-purified or recombinant hCG (rhCG) preparations. Subsequently, BMDC
      maturation was assessed. Cytokine secretion of activated BMDCs and their
      capability to enforce TH1, TH2, TH17, or Treg cell differentiation was determined
      after rhCG treatment. Moreover, the in vivo potential of hCG-modulated BMDCs to
      influence pregnancy outcome, Treg cell number, and local cytokine expression was
      evaluated after adoptive transfer in a murine abortion-prone model before and
      after conception. Both hCG preparations impaired the maturation process of BMDCs.
      rhCG treatment did neither alter cytokine secretion by BMDCs nor their ability to
      drive TH1, TH2, or TH17 differentiation. rhCG-treated BMDCs augmented the number
      of Treg cells within the T cell population. Adoptive transfer of rhCG-treated
      BMDCs after conception did not influence pregnancy outcome. However, transfer of
      hCG-treated BMDCs prior to mating had a protective effect on pregnancy. This
      positive effect was accompanied by increased Treg cell numbers and decidual IL-10
      and TGF-beta expression. Our results unveil the importance of hCG in retaining
      DCs in a tolerogenic state, thereby promoting Treg cell increment and supporting
      fetal survival.

PMID- 27895620
TI  - Excessive Cytosolic DNA Fragments as a Potential Trigger of Graves' Disease: An
      Encrypted Message Sent by Animal Models.
AB  - Graves' hyperthyroidism is caused by autoantibodies directed against the thyroid
      stimulating hormone receptor (TSHR) that mimic the action of TSH. The
      establishment of Graves' hyperthyroidism in experimental animals has proven to be
      an important approach to dissect the mechanisms of self-tolerance breakdown that
      lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs).
      "Shimojo's model" was the first successful Graves' animal model, wherein
      immunization with fibroblasts cells expressing TSHR and a major
      histocompatibility complex (MHC) class II molecule, but not either alone, induced
      TSAb production in AKR/N (H-2k) mice. This model highlights the importance of
      coincident MHC class II expression on TSHR-expressing cells in the development of
      Graves' hyperthyroidism. These data are also in agreement with the observation
      that Graves' thyrocytes often aberrantly express MHC class II antigens via
      mechanisms that remain unclear. Our group demonstrated that cytosolic self
      genomic DNA fragments derived from sterile injured cells can induce aberrant MHC
      class II expression and production of multiple inflammatory cytokines and
      chemokines in thyrocytes in vitro, suggesting that severe cell injury may
      initiate immune responses in a way that is relevant to thyroid autoimmunity
      mediated by cytosolic DNA signaling. Furthermore, more recent successful Graves'
      animal models were primarily established by immunizing mice with TSHR-expressing
      plasmids or adenovirus. In these models, double-stranded DNA vaccine contents
      presumably exert similar immune-activating effect in cells at inoculation sites
      and thus might pave the way toward successful Graves' animal models. This review
      focuses on evidence suggesting that cell injury-derived self-DNA fragments could
      act as Graves' disease triggers.

PMID- 27895622
TI  - Serum Zn/Cu Ratio Is Associated with Renal Function, Glycemic Control, and
      Metabolic Parameters in Japanese Patients with and without Type 2 Diabetes: A
      Cross-sectional Study.
AB  - BACKGROUND: Zinc (Zn) and copper (Cu) may play a pivotal role in the pathogenesis
      of diabetes and diabetic complications by mediating oxidative stress. Both Zn
      deficiency and excess of Cu are associated with an increased risk of type 2
      diabetes and cardiovascular disease. We aimed to investigate the relationships
      between serum Zn/Cu ratio and glycemic status, renal function, and metabolic
      parameters in patients with and without type 2 diabetes. METHODS: We conducted a
      cross-sectional study on 355 subjects (149 type 2 diabetic and 206 non-diabetic)
      in whom serum Zn and Cu levels were measured at the same time. Associations
      between serum Zn/Cu ratio and clinical data were evaluated using multiple
      regression analysis. We also evaluated associations between serum Zn/Cu ratio and
      the prevalence of type 2 diabetes and glycemic control by multivariate logistic
      regression analysis. RESULTS: Serum Zn/Cu ratio was positively associated with
      estimated glomerular filtration rate after adjustment for body mass index (BMI)
      (beta = 0.137, p = 0.014). Plasma B-type natriuretic peptide levels were
      negatively associated with serum Zn/Cu ratio after adjustment for age, sex, and
      BMI (beta = -0.258, p = 0.032). In patients with type 2 diabetes, serum Zn/Cu
      ratio was negatively associated with plasma HbA1c levels after adjustment for
      age, sex, and BMI (beta = -0.239, p = 0.003). In addition, multivariate logistic
      regression analysis revealed that the highest quartile of serum Zn/Cu ratio was
      associated with a reduced risk of poor (HbA1c >= 7%) glycemic control (odds ratio
      = 0.382; 95% confidence interval, 0.165-0.884; p = 0.025) in patients with type 2
      diabetes. CONCLUSION: Serum Zn/Cu ratio was favorably associated with renal
      function in all subjects and glycemic control in patients with type 2 diabetes.
      The Zn/Cu ratio, in addition to the individual serum levels of trace elements, is
      important for metabolism in humans.

PMID- 27895624
TI  - Visualizing Evolutionary Relationships of Multidomain Proteins: An Example from
      Receiver (REC) Domains of Sensor Histidine Kinases in the Candidatus
      Maribeggiatoa str. Orange Guaymas Draft Genome.
AB  - For multidomain proteins, evolutionary changes may occur at the domain as well as
      the whole-protein level. An example is presented here, with suggestions for how
      such complicated relationships might be visualized. Earlier analysis of the
      Candidatus Maribeggiatoa str. Orange Guaymas (BOGUAY; Gammaproteobacteria) single
      filament draft genome found evidence of gene exchange with the phylogenetically
      distant Cyanobacteria, particularly for sensory and signal transduction proteins.
      Because these are modular proteins, known to undergo frequent duplication, domain
      swapping, and horizontal gene transfer, a single domain was chosen for analysis.
      Recognition (REC) domains are short (~125 amino acids) and well conserved,
      simplifying sequence alignments and phylogenetic calculations. Over 100 of these
      were identified in the BOGUAY genome and found to have a wide range of inferred
      phylogenetic relationships. Two sets were chosen here for detailed study. One set
      of four BOGUAY ORFs has closest relatives among other Beggiatoaceae and
      Cyanobacteria. A second set of four has REC domains with more mixed affiliations,
      including other Beggiatoaceae, several sulfate-reducing Deltaproteobacteria and
      Firmicutes, magnetotactic Nitrospirae, one Shewanella and one Ferrimonas strain
      (both Gammaproteobacteria), and numerous Vibrio vulnificus and V. navarrensis
      strains (also Gammaproteobacteria). For an overview of the possible origins of
      the whole proteins and the surrounding genomic regions, color-coded BLASTP
      results were produced and displayed against cartoons showing protein domain
      structure of predicted genes. This is suggested as a visualization method for
      investigation of possible horizontally transferred regions, giving more detail
      than scans of DNA composition and codon usage but much faster than carrying out
      full phylogenetic analyses for multiple proteins. As expected, most of the
      predicted sensor histidine kinases investigated have two or more segments with
      distinct BLASTP affiliations. For the first set of BOGUAY ORFs, the flanking
      regions were also examined, and the results suggest they are embedded in genomic
      stretches with complex histories. An automated method of creating such
      visualizations could be generally useful; a wish list for its features is given.

PMID- 27895623
TI  - Molecular Approaches to Screen Bioactive Compounds from Endophytic Fungi.
AB  - Endophytic fungi are capable of producing plant associated metabolites and their
      analogs with therapeutic value. In order to identify the potential endophytic
      isolates producing bioactive compounds, one need to screen all isolated
      endophytes, which may run into hundreds. Isolation of endophytic fungi is
      relatively a simple process; but screening of the isolated fungi for required
      metabolite production is a cumbersome process. Endophytic fungi producing plant
      associated metabolites may contain genes involved in the entire biosynthetic
      pathway(s). Therefore, ascertaining the presence of key enzymes of a particular
      biosynthetic pathway could serve as a molecular marker for screening of these
      endophytes to produce that metabolite. In absence of entire biosynthetic pathways
      in endophytic fungi, plant genes associated with that metabolic pathway could
      serve as markers. This review focuses on the impact of molecular approaches to
      screen the endophytic fungi for the production of bioactive compounds. An attempt
      has been made on screening of anticancer compounds like taxol (paclitaxel),
      podophyllotoxin, and camptothecin using molecular markers. The advantages of
      molecular approaches over conventional methods to screen endophytic fungi and
      also identification of endophytic fungi are discussed.

PMID- 27895626
TI  - A Proposal for Formation of Archaean Stromatolites before the Advent of Oxygenic
      Photosynthesis.
AB  - Stromatolites are solid, laminar structures of biological origin. Living examples
      are sparsely distributed and formed by cyanobacteria, which are oxygenic
      phototrophs. However, stromatolites were abundant between 3.4 and 2.4 Gyr, prior
      to the advent of cyanobacteria and oxygenic photosynthesis. Here I propose that
      many Archaean stromatolites were seeded at points of efflux of hydrogen sulfide
      from hydrothermal fields into shallow water, while their laminar composition
      arose from alternating modes of strictly anoxygenic photosynthetic metabolism.
      These changes were a redox regulatory response of gene expression to changing
      hydrogen sulfide concentration, which fluctuated with intermittent dilution by
      tidal action or by rainfall into surface waters. The proposed redox switch
      between modes of metabolism deposited sequential microbial mats. These mats gave
      rise to alternating carbonate sediments predicted to retain evidence of their
      origin in differing ratios of isotopes of carbon and sulfur and in organic
      content. The mats may have arisen either by replacement of microbial populations
      or by continuous lineages of protocyanobacteria in which a redox genetic switch
      selected between Types I and II photosynthetic reaction centers, and thus between
      photolithoautotrophic and photoorganoheterotrophic metabolism. In the latter
      case, and by 2.4 Gyr at the latest, a mutation had disabled the redox genetic
      switch to give simultaneous constitutive expression of both Types I and II
      reaction centers, and thus to the ability to extract electrons from manganese and
      then water. By this simple step, the first cyanobacterium had the dramatic
      advantage of emancipation from limiting supplies of inorganic electron donors,
      produced free molecular oxygen as a waste product, and initiated the Great
      Oxidation Event in Earth's history at the transition from the Archaean to the
      Paleoproterozoic.

PMID- 27895625
TI  - Evaluation of Virulence Factors In vitro, Resistance to Osmotic Stress and
      Antifungal Susceptibility of Candida tropicalis Isolated from the Coastal
      Environment of Northeast Brazil.
AB  - Several studies have been developed regarding human health risks associated with
      the recreational use of beaches contaminated with domestic sewage. These wastes
      contain various micro-organisms, including Candida tropicalis. In this context,
      the objective of this study was to characterize C. tropicalis isolates from the
      sandy beach of Ponta Negra, Natal, Rio Grande do Norte, Brazil, regarding the
      expression of in vitro virulence factors, adaptation to osmotic stress and
      susceptibility to antifungal drugs. We analyzed 62 environmental isolates and
      observed a great variation among them for the various virulence factors
      evaluated. In general, environmental isolates were more adherent to human buccal
      epithelial cells (HBEC) than C. tropicalis ATCC13803 reference strain, and they
      also showed increased biofilm production. Most of the isolates presented wrinkled
      phenotypes on Spider medium (34 isolates, 54.8%). The majority of the isolates
      also showed higher proteinase production than control strains, but low
      phospholipase activity. In addition, 35 isolates (56.4%) had high hemolytic
      activity (hemolysis index > 0.55). With regard to C. tropicalis resistance to
      osmotic stress, 85.4% of the isolates were able to grow in a liquid medium
      containing 15% sodium chloride. The strains were highly resistant to the azoles
      tested (fluconazole, voriconazole and itraconazole). Fifteen strains were
      resistant to the three azoles tested (24.2%). Some strains were also resistant to
      amphotericin B (14 isolates; 22.6%), while all of them were susceptible for the
      echinocandins tested, except for a single strain of intermediate susceptibility
      to micafungin. Our results demonstrate that C. tropicalis isolated from the sand
      can fully express virulence attributes and showed a high persistence capacity on
      the coastal environment; in addition of showing high minimal inhibitory
      concentrations to several antifungal drugs used in current clinical practice,
      demonstrating that environmental isolates may have pathogenic potential.

PMID- 27895628
TI  - Nearshore Pelagic Microbial Community Abundance Affects Recruitment Success of
      Giant Kelp, Macrocystis pyrifera.
AB  - Marine microbes mediate key ecological processes in kelp forest ecosystems and
      interact with macroalgae. Pelagic and biofilm-associated microbes interact with
      macroalgal propagules at multiple stages of recruitment, yet these interactions
      have not been described for Macrocystis pyrifera. Here we investigate the
      influence of microbes from coastal environments on recruitment of giant kelp, M.
      pyrifera. Through repeated laboratory experiments, we tested the effects of
      altered pelagic microbial abundance on the settlement and development of the
      microscopic propagules of M. pyrifera during recruitment. M. pyrifera zoospores
      were reared in laboratory microcosms exposed to environmental microbial
      communities from seawater during the complete haploid stages of the kelp
      recruitment cycle, including zoospore release, followed by zoospore settlement,
      to gametophyte germination and development. We altered the microbial abundance
      states differentially in three independent experiments with repeated trials,
      where microbes were (a) present or absent in seawater, (b) altered in community
      composition, and (c) altered in abundance. Within the third experiment, we also
      tested the effect of nearshore versus offshore microbial communities on the
      macroalgal propagules. Distinct pelagic microbial communities were collected from
      two southern California temperate environments reflecting contrasting intensity
      of human influence, the nearshore Point Loma kelp forest and the offshore Santa
      Catalina Island kelp forest. The Point Loma kelp forest is a high impacted
      coastal region adjacent to the populous San Diego Bay; whereas the kelp forest at
      Catalina Island is a low impacted region of the Channel Islands, 40 km offshore
      the southern California coast, and is adjacent to a marine protected area. Kelp
      gametophytes reared with nearshore Point Loma microbes showed lower survival,
      growth, and deteriorated morphology compared to gametophytes with the offshore
      Catalina Island microbial community, and these effects were magnified under high
      microbial abundances. Reducing abundance of Point Loma microbes restored M.
      pyrifera propagule success. Yet an intermediate microbial abundance was optimal
      for kelp propagules reared with Catalina Island microbes, suggesting that
      microbes also have a beneficial influence on kelp. Our study shows that pelagic
      microbes from nearshore and offshore environments are differentially influencing
      kelp propagule success, which has significant implications for kelp recruitment
      and kelp forest ecosystem health.

PMID- 27895627
TI  - Distribution and Classification of Serine beta-Lactamases in Brazilian Hospital
      Sewage and Other Environmental Metagenomes Deposited in Public Databases.
AB  - beta-lactam is the most used antibiotic class in the clinical area and it acts on
      blocking the bacteria cell wall synthesis, causing cell death. However, some
      bacteria have evolved resistance to these antibiotics mainly due the production
      of enzymes known as beta-lactamases. Hospital sewage is an important source of
      dispersion of multidrug-resistant bacteria in rivers and oceans. In this work, we
      used next-generation DNA sequencing to explore the diversity and dissemination of
      serine beta-lactamases in two hospital sewage from Rio de Janeiro, Brazil (South
      Zone, SZ and North Zone, NZ), presenting different profiles, and to compare them
      with public environmental data available. Also, we propose a Hidden-Markov-Model
      approach to screen potential serine beta-lactamases genes (in public environments
      samples and generated hospital sewage data), exploring its evolutionary
      relationships. Due to the high variability in beta-lactamases, we used a position
      specific scoring matrix search method (RPS-BLAST) against conserved domain
      database profiles (CDD, Pfam, and COG) followed by visual inspection to detect
      conserved motifs, to increase the reliability of the results and remove possible
      false positives. We were able to identify novel beta-lactamases from Brazilian
      hospital sewage and to estimate relative abundance of its types. The highest
      relative abundance found in SZ was the Class A (50%), while Class D is
      predominant in NZ (55%). CfxA (65%) and ACC (47%) types were the most abundant
      genes detected in SZ, while in NZ the most frequent were OXA-10 (32%), CfxA
      (28%), ACC (21%), CEPA (20%), and FOX (19%). Phylogenetic analysis revealed beta
      lactamases from Brazilian hospital sewage grouped in the same clade and close to
      sequences belonging to Firmicutes and Bacteroidetes groups, but distant from
      potential beta-lactamases screened from public environmental data, that grouped
      closer to beta-lactamases of Proteobacteria. Our results demonstrated that HMM
      based approach identified homologs of serine beta-lactamases, indicating the
      specificity and high sensitivity of this approach in large datasets, contributing
      for the identification and classification of a large number of homologous genes,
      comprising possible new ones. Phylogenetic analysis revealed the potential
      reservoir of beta-lactam resistance genes in the environment, contributing to
      understanding the evolution and dissemination of these genes.

PMID- 27895629
TI  - Genome-Wide Discovery of Putative sRNAs in Paracoccus denitrificans Expressed
      under Nitrous Oxide Emitting Conditions.
AB  - Nitrous oxide (N2O) is a stable, ozone depleting greenhouse gas. Emissions of N2O
      into the atmosphere continue to rise, primarily due to the use of nitrogen
      containing fertilizers by soil denitrifying microbes. It is clear more effective
      mitigation strategies are required to reduce emissions. One way to help develop
      future mitigation strategies is to address the currently poor understanding of
      transcriptional regulation of the enzymes used to produce and consume N2O. With
      this ultimate aim in mind we performed RNA-seq on a model soil denitrifier,
      Paracoccus denitrificans, cultured anaerobically under high N2O and low N2O
      emitting conditions, and aerobically under zero N2O emitting conditions to
      identify small RNAs (sRNAs) with potential regulatory functions transcribed under
      these conditions. sRNAs are short (~40-500 nucleotides) non-coding RNAs that
      regulate a wide range of activities in many bacteria. Hundred and sixty seven
      sRNAs were identified throughout the P. denitrificans genome which are either
      present in intergenic regions or located antisense to ORFs. Furthermore, many of
      these sRNAs are differentially expressed under high N2O and low N2O emitting
      conditions respectively, suggesting they may play a role in production or
      reduction of N2O. Expression of 16 of these sRNAs have been confirmed by RT-PCR.
      Ninety percent of the sRNAs are predicted to form secondary structures. Predicted
      targets include transporters and a number of transcriptional regulators. A number
      of sRNAs were conserved in other members of the alpha-proteobacteria. Better
      understanding of the sRNA factors which contribute to expression of the machinery
      required to reduce N2O will, in turn, help to inform strategies for mitigation of
      N2O emissions.

PMID- 27895631
TI  - Cooperative Recruitment of FtsW to the Division Site of Bacillus subtilis.
AB  - Five essential proteins are known to assemble at the division site of Bacillus
      subtilis. However, the recruitment of the FtsW homolog is still unclear. Here, we
      take advantage of spore germination to facilitate the depletion of essential
      proteins and to study the divisome assembly in the absence of previous division
      events. We show that, unlike what has been shown for the Escherichia coli
      divisome, the assembly of FtsW is interdependent with the localization of PBP 2B
      and FtsL, which are key components of the membrane bound division complex.
      Interestingly, the Z-ring appeared to disassemble upon prolonged depletion of
      late division proteins. Nevertheless, we could restore Z-ring formation and
      constriction by re-inducing FtsW, which suggests that the stability of the Z-ring
      is stimulated by the assembly of a functional division complex.

PMID- 27895632
TI  - Predicting Resistance by Mutagenesis: Lessons from 45 Years of MBC Resistance.
AB  - When a new fungicide class is introduced, it is useful to anticipate the
      resistance risk in advance, attempting to predict both risk level and potential
      mechanisms. One tool for the prediction of resistance risk is laboratory
      selection for resistance, with the mutational supply increased through UV or
      chemical mutagenesis. This enables resistance to emerge more rapidly than in the
      field, but may produce mutations that would not emerge under field conditions.
      The methyl benzimidazole carbamates (MBCs) were the first systemic single-site
      agricultural fungicides, and the first fungicides affected by rapid evolution of
      target-site resistance. MBC resistance has now been reported in over 90 plant
      pathogens in the field, and laboratory mutants have been studied in nearly 30
      species. The most common field mutations, including beta-tubulin E198A/K/G, F200Y
      and L240F, have all been identified in laboratory mutants. However, of 28
      mutations identified in laboratory mutants, only nine have been reported in the
      field. Therefore, the predictive value of mutagenesis studies would be increased
      by understanding which mutations are likely to emerge in the field. Our review of
      the literature indicates that mutations with high resistance factors, and those
      found in multiple species, are more likely to be reported in the field. However,
      there are many exceptions, possibly due to fitness penalties. Whether a mutation
      occurred in the same species appears less relevant, perhaps because beta-tubulin
      is highly conserved so functional constraints are similar across all species.
      Predictability of mutations in other target sites will depend on the level and
      conservation of constraints.

PMID- 27895630
TI  - Comparative Functional Genomic Analysis of Two Vibrio Phages Reveals Complex
      Metabolic Interactions with the Host Cell.
AB  - Sequencing and annotation was performed for two large double stranded DNA
      bacteriophages, phiGrn1 and phiSt2 of the Myoviridae family, considered to be of
      great interest for phage therapy against Vibrios in aquaculture live feeds. In
      addition, phage-host metabolic interactions and exploitation was studied by
      transcript profiling of selected viral and host genes. Comparative genomic
      analysis with other large Vibrio phages was also performed to establish the
      presence and location of homing endonucleases highlighting distinct features for
      both phages. Phylogenetic analysis revealed that they belong to the
      "schizoT4like" clade. Although many reports of newly sequenced viruses have
      provided a large set of information, basic research related to the shift of the
      bacterial metabolism during infection remains stagnant. The function of many
      viral protein products in the process of infection is still unknown. Genome
      annotation identified the presence of several viral open reading frames (ORFs)
      participating in metabolism, including a Sir2/cobB (sirtuin) protein and a number
      of genes involved in auxiliary NAD+ and nucleotide biosynthesis, necessary for
      phage DNA replication. Key genes were subsequently selected for detail study of
      their expression levels during infection. This work suggests a complex metabolic
      interaction and exploitation of the host metabolic pathways and biochemical
      processes, including a possible post-translational protein modification, by the
      virus during infection.

PMID- 27895633
TI  - Detection of sdhB Gene Mutations in SDHI-Resistant Isolates of Botrytis cinerea
      Using High Resolution Melting (HRM) Analysis.
AB  - Botrytis cinerea, is a high risk pathogen for fungicide resistance development.
      Pathogen' resistance to SDHIs is associated with several mutations in sdh gene.
      The diversity of mutations and their differential effect on cross-resistance
      patterns among SDHIs and the fitness of resistant strains necessitate the
      availability of a tool for their rapid identification. This study was initiated
      to develop and validate a high-resolution melting (HRM) analysis for the
      identification of P225H/F/L//T, N230I, and H272L/R/Y mutations. Based on the
      sequence of sdhB subunit of resistant and sensitive isolates, a universal primer
      pair was designed. The specificity of the HRM analysis primers was verified to
      ensure against the cross-reaction with other fungal species and its sensitivity
      was evaluated using concentrations of known amounts of mutant's DNA. The melting
      curve analysis generated nine distinct curve profiles, enabling the
      discrimination of all the four mutations located at codon 225, the N230I
      mutation, the three mutations located in codon 272, and the non-mutated isolates
      (isolates of wild-type sensitivity). Similar results were obtained when DNA was
      extracted directly from artificially inoculated strawberry fruit. The method was
      validated by monitoring the presence of sdhB mutations in samples of naturally
      infected strawberry fruits and stone fruit rootstock seedling plants showing
      damping-off symptoms. HRM analysis data were compared with a standard PIRA-PCR
      technique and an absolute agreement was observed suggesting that in both
      populations the H272R mutation was the predominant one, while H272Y, N230I, and
      P225H were detected in lower frequencies. The results of the study suggest that
      HRM analysis can be a useful tool for sensate, accurate, and rapid identification
      of several sdhB mutations in B. cinerea and it is expected to contribute in
      routine fungicide resistance monitoring or assessments of the effectiveness of
      anti-resistance strategies implemented in crops heavily treated with
      botryticides.

PMID- 27895634
TI  - Cytosolic Proteome Profiling of Aminoglycosides Resistant Mycobacterium
      tuberculosis Clinical Isolates Using MALDI-TOF/MS.
AB  - Emergence of extensively drug resistant tuberculosis (XDR-TB) is the consequence
      of the failure of second line TB treatment. Aminoglycosides are the important
      second line anti-TB drugs used to treat the multi drug resistant tuberculosis
      (MDR-TB). Main known mechanism of action of aminoglycosides is to inhibit the
      protein synthesis by inhibiting the normal functioning of ribosome. Primary
      target of aminoglycosides are the ribosomal RNA and its associated proteins.
      Various mechanisms have been proposed for aminoglycosides resistance but still
      some are unsolved. As proteins are involved in most of the biological processes,
      these act as a potential diagnostic markers and drug targets. In the present
      study we analyzed the purely cytosolic proteome of amikacin (AK) and kanamycin
      (KM) resistant Mycobacterium tuberculosis isolates by proteomic and bioinformatic
      approaches. Twenty protein spots were found to have over expressed in resistant
      isolates and were identified. Among these Rv3208A, Rv2623, Rv1360, Rv2140c,
      Rv1636, and Rv2185c are six proteins with unknown functions or undefined role.
      Docking results showed that AK and KM binds to the conserved domain (DUF, USP-A,
      Luciferase, PEBP and Polyketidecyclase/dehydrase domain) of these hypothetical
      proteins and over expression of these proteins might neutralize/modulate the
      effect of drug molecules. TBPred and GPS-PUP predicted cytoplasmic nature and
      potential pupylation sites within these identified proteins, respectively. String
      analysis also suggested that over expressed proteins along with their interactive
      partners might be involved in aminoglycosides resistance. Cumulative effect of
      these over expressed proteins could be involved in AK and KM resistance by
      mitigating the toxicity, repression of drug target and neutralizing affect. These
      findings need further exploitation for the expansion of newer therapeutics or
      diagnostic markers against AK and KM resistance so that an extreme condition like
      XDR-TB can be prevented.

PMID- 27895636
TI  - Genomic and Transcriptomic Evidence for Carbohydrate Consumption among
      Microorganisms in a Cold Seep Brine Pool.
AB  - The detailed lifestyle of microorganisms in deep-sea brine environments remains
      largely unexplored. Using a carefully calibrated genome binning approach, we
      reconstructed partial to nearly-complete genomes of 51 microorganisms in biofilms
      from the Thuwal cold seep brine pool of the Red Sea. The recovered metagenome
      assembled genomes (MAGs) belong to six different phyla: Actinobacteria,
      Proteobacteria, Candidatus Cloacimonetes, Candidatus Marinimicrobia,
      Bathyarchaeota, and Thaumarchaeota. By comparison with close relatives of these
      microorganisms, we identified a number of unique genes associated with organic
      carbon metabolism and energy generation. These genes included various glycoside
      hydrolases, nitrate and sulfate reductases, putative bacterial microcompartment
      biosynthetic clusters (BMC), and F420H2 dehydrogenases. Phylogenetic analysis
      suggested that the acquisition of these genes probably occurred through
      horizontal gene transfer (HGT). Metatranscriptomics illustrated that glycoside
      hydrolases are among the most highly expressed genes. Our results suggest that
      the microbial inhabitants are well adapted to this brine environment, and
      anaerobic carbohydrate consumption mediated by glycoside hydrolases and electron
      transport systems (ETSs) is a dominant process performed by microorganisms from
      various phyla within this ecosystem.

PMID- 27895635
TI  - Molecular Characteristic and Virulence Gene Profiles of Community-Associated
      Methicillin-Resistant Staphylococcus aureus Isolates from Pediatric Patients in
      Shanghai, China.
AB  - Staphylococcus aureus is a globally important human pathogen, especially among
      children and immunocompromised patients. The emergence and spread of community
      associated methicillin-resistant S. aureus (CA-MRSA) has become a serious public
      health problem worldwide. The aim of this study was to investigate the
      prevalence, molecular characteristics and virulence profiles of CA-MRSA
      infections from pediatric patients in a university hospital in Shanghai, China. A
      total of 80 CA-MRSA isolates were collected from July 2012 to December 2013 in
      Shanghai Children's Medical Center and analyzed by multilocus sequence typing,
      staphylococcus chromosomal cassette mec (SCCmec) typing, and spa typing. The
      detection of Panton-Valentine Leukocidin (pvl), superantigenic and exfoliative
      toxins, and adhesin genes was also performed. Overall, 16 distinct sequence types
      (STs) were identified among the 80 isolates. Among them, ST59 was found to be the
      most prevalent, followed by ST398 (11.3%, 9/80) and ST88 (8.8%, 7/80). SCCmec
      types IV and V were observed, at 60 and 40%, respectively. Thirty spa types were
      identified, spa t437 (23.8%) was the most predominant type. All 80 isolates
      exhibited carriage of at least four virulence genes. Thirty-four (42.5%, 34/80)
      isolates harbored >=10 tested virulence genes. Adhesion genes were present in
      most of the MRSA isolates, including the following: icaA (100%), clfA (100%),
      sdrC (95%), and sdrE (63.8%). The prevalence of pvl gene was 20%, and multidrug
      resistance was observed in 36% of all strains. In addition, ST59-MRSA-IV with
      t437 accounted for 21.3% of occurrences, making it the most prevalent clone.
      Isolates that were carriers of toxin genes, and hla (100%) and hlg (87.5%) were
      the most frequent. In conclusion, simultaneous carriage of multiple virulence
      genes and genetically considerable diversity were very common among CA-MRSA from
      pediatric patients in Shanghai. ST59-MRSA-IV with t437 was still the most
      predominant type. The combination of virulence gene profiles and antibiotic
      resistance may help ST59 to be successfully spread among children.

PMID- 27895637
TI  - High Prevalence of ESBL-Producing Klebsiella pneumoniae Causing Community-Onset
      Infections in China.
AB  - The aim of this work was to investigate the epidemiological and genetic
      characteristics of ESBL-producing Klebsiella pneumoniae (ESBL-Kp) causing
      community-onset infections. K. pneumoniae isolates were collected from 31 Chinese
      secondary hospitals between August 2010 and 2011. Genes encoding ESBL and AmpC
      beta-lactamases were detected by PCR. The isolates were assigned to sequence
      types (STs) using multi-locus sequence typing (MLST). Eleven ESBL-Kp strains were
      selected for whole-genome sequencing (WGS) for investigating the genetic
      environment and plasmids encoding ESBL genes. A total of 578 K. pneumoniae
      isolates were collected, and 184 (31.8%) carried ESBL genes. The prevalence of
      ESBL-Kp varied from different geographical areas of China (10.2-50.3%). The three
      most prevalent ESBL genes were blaCTX-M-14 (n = 74), blaCTX-M-15 (n = 60), and
      blaCTX-M-3 (n = 40). MLST assigned 127 CTX-M-14 and CTX-M-15 producers to 54 STs,
      and CC17 was the most prevalent population (12.6%). STs (23, 37, and 86) that
      were known frequently associated with hypervirulent K. pneumoniae (hvKP) account
      for 14.1% (18/127). Phylogenetic analysis by concatenating the seven loci of MLST
      revealed the existence of ESBL-producing K. quasipneumoniae (two strains) and K.
      varricola (one strain), which was further confirmed by WGS. This study highlights
      the challenge of community-onset infections caused by ESBL-Kp in China. The
      prevalence of STs frequently associating with hvKP should be of concern.
      Surveillance of ESBL-KP causing community-onset infections now appears
      imperative.

PMID- 27895638
TI  - Intercellular Interactions as Regulators of NETosis.
AB  - Neutrophil extracellular traps (NETs) are chromatin-derived webs extruded from
      neutrophils in response to either infection or sterile stimulation with
      chemicals, cytokines, or microbial products. The vast majority of studies have
      characterized NET release (also called NETosis) in pure neutrophil cultures in
      vitro. The situation is surely more complex in vivo as neutrophils constantly
      sample not only pathogens and soluble mediators but also signals from cellular
      partners, including platelets and endothelial cells. This complexity is beginning
      to be explored by studies utilizing in vitro co-culture, as well as animal models
      of sepsis, infective endocarditis, lung injury, and thrombosis. Indeed, various
      selectins, integrins, and surface glycoproteins have been implicated in platelet
      neutrophil interactions that promote NETosis, albeit with disparate results
      across studies. NETosis can also clearly be regulated by soluble mediators
      derived from platelets, such as eicosanoids, chemokines, and alarmins. Beyond
      platelets, the role of the endothelium in modulating NETosis is being
      increasingly revealed, with adhesive interactions likely priming neutrophils
      toward NETosis. The fact that the same selectins and surface glycoproteins may be
      expressed by both platelets and endothelial cells complicates the interpretation
      of in vivo data. In summary, we suggest in this review that the engagement of
      neutrophils with activated cellular partners provides an important in vivo signal
      or "hit" toward NETosis. Studies should, therefore, increasingly consider the
      triumvirate of neutrophils, platelets, and the endothelium when exploring
      NETosis, especially in disease states.

PMID- 27895639
TI  - NETosis as Source of Autoantigens in Rheumatoid Arthritis.
AB  - In neutrophils (but also in eosinophils and in mast cells), different
      inflammatory stimuli induce histone deimination, chromatin decondensation, and
      NET formation. These web-like structures that trap and kill microbes contain DNA,
      cationic granule proteins, and antimicrobial peptides, but the most abundant
      proteins are core histones. Histones contained in NETs have been deiminated, and
      arginines are converted in citrullines. While deimination is a physiological
      process amplified in inflammatory conditions, only individuals carrying genetic
      predisposition to develop rheumatoid arthritis (RA) make antibodies to deiminated
      proteins. These antibodies, collectively identified as anti-citrullinated
      proteins/peptides antibodies (ACPA), react with different deiminated proteins and
      display partially overlapping specificities. In this paper, we will summarize
      current evidence supporting the role of NETosis as critical mechanism in the
      breach of tolerance to self-antigens and in supporting expansion and
      differentiation of autoreactive cells. In fact, several lines of evidence connect
      NETosis with RA: RA unstimulated synovial fluid neutrophils display enhanced
      NETosis; sera from RA patients with Felty's syndrome bind deiminated H3 and NETs;
      a high number of RA sera bind deiminated H4 contained in NETs; human monoclonal
      antibodies generated from RA synovial B cells decorate NETs and bind deiminated
      histones. In RA, NETs represent on one side an important source of autoantigens
      bearing posttranslational modifications and fueling the production of ACPA. On
      the other side, NETs deliver signals that maintain an inflammatory milieu and
      contribute to the expansion and differentiation of ACPA-producing B cells.

PMID- 27895640
TI  - omega3 Polyunsaturated Fatty Acids as Immunomodulators in Colorectal Cancer: New
      Potential Role in Adjuvant Therapies.
AB  - Diet composition may affect the onset and progression of chronic degenerative
      diseases, including cancer, whose pathogenesis relies on inflammatory processes.
      Growing evidence indicates that diet and its components critically contribute to
      human health, affecting the immune system, secretion of adipokines, and metabolic
      pathways. Colorectal cancer (CRC) is one of the leading causes of death
      worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug
      resistance and/or off-target toxicity limit their efficacy. Dietary omega3
      polyunsaturated fatty acids (PUFA) have been gaining great interest in recent
      years as possible anti-inflammatory and anticancer agents, especially in areas
      such as the large bowel, where the pro-inflammatory context promotes virtually
      all steps of colon carcinogenesis. Growing epidemiological, experimental, and
      clinical evidence suggests that omega3 PUFA may play a role in several stages of
      CRC management exhibiting antineoplastic activity against human CRC cells,
      improving the efficacy of radiation and chemotherapy, ameliorating cancer
      associated secondary complications, and preventing CRC recurrence. These effects
      are most likely related to the immunomodulatory activities of omega3 PUFA that
      are able to influence several aspects of the inflammatory process ranging from
      inflammasome activation, leukocyte recruitment, production of immune mediators to
      differentiation, and activation of immune cells. In this review, we will focus on
      the potential use of omega3 PUFA as adjuvant agents together with
      chemo/radiotherapy, highlighting the immunomodulatory effects most likely
      responsible for their beneficial effects in different stages of CRC management.

PMID- 27895641
TI  - Pneumococcal Polysaccharide Vaccination Elicits IgG Anti-A/B Blood Group
      Antibodies in Healthy Individuals and Patients with Type I Diabetes Mellitus.
AB  - HYPOTHESIS: Blood group antibodies are natural antibodies that develop early in
      life in response to cross-reactive environmental antigens in the absence of
      antigen encounter. Even later in life structural similarities in saccharide
      composition between environmental antigens such as bacterial polysaccharides and
      blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype,
      and affinity maturation of blood group anti-A/B antibodies. We addressed the
      question whether immunization with pneumococcal polysaccharide (PnP) vaccine
      Pneumo 23 Vaccine "Pasteur Merieux" (Pn23) could have such an effect in patients
      with type I diabetes mellitus (DM I), an autoimmune disease where an aberrant
      immune response to microbial antigens likely plays a role. METHODS: Anti-PnP IgM
      and IgG responses were determined by ELISA, and the DiaMed-ID Micro Typing System
      was used to screen anti-A/B antibody titer before and after Pn23 immunization in
      28 healthy individuals and 16 patients with DM I. In addition, surface plasmon
      resonance (SPR) technology using the Biacore(r) device and a synthetic blood
      group A/B trisaccharide as the antigen was applied to investigate IgM and IgG
      anti-A/B antibodies and to measure antibody binding dynamics. RESULTS: All
      healthy individuals and DM I patients responded with anti-PnP IgM and IgG
      antibody production 4-6 weeks after Pn23 immunization, while no increase in blood
      group anti-A/B antibody titer was observed when measured by the DiaMed-ID Micro
      Typing System. Interestingly, isotype-specific testing by SPR technology revealed
      an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization
      in both patients and controls. No change in binding characteristics of blood
      group anti-A/B antibodies could be detected following Pn23 vaccination,
      supporting the assumption of an increase in IgG antibody titer with no or very
      little affinity maturation. CONCLUSION: The study provides evidence for epitope
      sharing between pneumococcal polysaccharides and blood group ABO antigens, which
      leads to a booster of blood group anti-A/B antibodies of the IgG isotype after
      Pn23 immunization in healthy individuals. Manifest autoimmunity such as present
      in DM I patients has no additional effect on the cross-reactive antibody response
      against pneumococcal polysaccharides and blood group antigens.

PMID- 27895642
TI  - Functional and Structural Characterization of a Novel HLA-DRB1*04:01-Restricted
      alpha-Enolase T Cell Epitope in Rheumatoid Arthritis.
AB  - Antibodies to citrullinated proteins, common in rheumatoid arthritis (RA)
      patients, are strongly associated to a specific set of HLA-DR alleles including
      HLA-DRB1*04:01, *04:04, and *01:01. Here, we first demonstrate that autoantibody
      levels toward the dominant citrullinated B cell epitope from alpha-enolase are
      significantly elevated in HLA-DRB1*04:01-positive RA patients. Furthermore, we
      identified alpha-enolase-derived T cell epitopes and demonstrated that native and
      citrullinated versions of several peptides bind with different affinities to HLA
      DRB1*04:01, *04:04, and *01:01. The citrulline residues in the eight identified
      peptides are distributed throughout the entire length of the presented epitopes
      and more specifically, localized at peptide positions p-2, p2, p4, p6, p7, p10,
      and p11. Importantly, in contrast to its native version peptide 26
      (TSKGLFRAAVPSGAS), the HLA-DRB1*04:01-restricted citrullinated peptide Cit26
      (TSKGLFCitAAVPSGAS) elicited significant functional T cell responses in primary
      cells from RA patients. Comparative analysis of the crystal structures of HLA
      DRB1*04:01 in complex with peptide 26 or Cit26 demonstrated that the
      posttranslational modification did not alter the conformation of the peptide. And
      since citrullination is the only structural difference between the two complexes,
      this indicates that the neo-antigen Cit26 is recognized by T cells with high
      specificity to the citrulline residue.

PMID- 27895643
TI  - Azithromycin Attenuates Pseudomonas-Induced Lung Inflammation by Targeting
      Bacterial Proteins Secreted in the Cultured Medium.
AB  - BACKGROUND: Pseudomonas aeruginosa airway infections are a major cause of
      morbidity and mortality in patients with cystic fibrosis (CF). Azithromycin
      improves the related clinical outcomes, but its mechanisms of action remain
      poorly understood. We tested the hypothesis that azithromycin downregulates P.
      aeruginosa-induced pro-inflammatory responses by modifying release of bacterial
      proteins. METHODS: We monitored inflammatory markers in lungs of CF mutant mice
      and their littermate controls in response to conditioned media (CM) collected
      from the reference P. aeruginosa PAO1 strain cultured in the presence or in the
      absence of azithromycin. A mass spectrometry-based proteomic approach was applied
      to examine whether the macrolide elicits a differential release of bacterial
      proteins. RESULTS: CM collected from azithromycin-untreated PAO1 cultures induced
      powerful pro-inflammatory neutrophil-dominated responses. Azithromycin attenuated
      the responses, mainly of macrophage chemoattractant protein-1, tumor necrosis
      factor-alpha, and interferon-gamma, in CF but not in wild-type mice. Proteomic
      analysis showed that azithromycin upregulated an array of bacterial proteins
      including those associated with regulation of immune functions and with repair
      and resolution of inflammatory responses like the chaperone DnaK and the S
      adenosylmethionine synthase, while it downregulated the extracellular heme
      acquisition protein HasA and the catalytic enzyme lysylendopeptidase. CONCLUSION:
      Supernatants collected from cultures of the bacterial strain PAO1 represent a
      novel experimental model to trigger in vivo lung inflammatory responses that
      should be closer to those obtained with live bacteria, but without bacterial
      infection. Combined with a bactericidal effect, complex regulation of bacterial
      innate immune and metabolic factors released in the cultured medium by the action
      of the macrolide can contribute to its anti-inflammatory effects.

PMID- 27895648
TI  - Grape Ripening Is Regulated by Deficit Irrigation/Elevated Temperatures According
      to Cluster Position in the Canopy.
AB  - The impact of water deficit on berry quality has been extensively investigated
      during the last decades. Nonetheless, there is a scarcity of knowledge on the
      performance of varieties exposed to a combination of high temperatures/water
      stress during the growing season and under vineyard conditions. The objective of
      this research was to investigate the effects of two irrigation regimes, sustained
      deficit irrigation (SDI, 30% ETc) and regulated deficit irrigation (RDI, 15% ETc)
      and of two cluster positions within the canopy (east- and west-exposed sides) on
      berry ripening in red Aragonez (Tempranillo) grapevines. The study was undertaken
      for two successive years in a commercial vineyard in South Portugal, monitoring
      the following parameters: pre-dawn leaf water potential, berry temperature,
      sugars, polyphenols, abscisic acid (ABA) and related metabolites. Additionally,
      expression patterns for different transcripts encoding for enzymes responsible
      for anthocyanin and ABA biosynthesis (VviUFGT, VvNCED1, VvbetaG1, VviHyd1,
      VviHyd2) were analyzed. In both years anthocyanin concentration was lower in RDI
      at the west side (RDIW- the hottest one) from veraison onwards, suggesting that
      the most severe water stress conditions exacerbated the negative impact of high
      temperature on anthocyanin. The down-regulation of VviUFGT expression revealed a
      repression of the anthocyanin synthesis in berries of RDIW, at early stages of
      berry ripening. At full-maturation, anthocyanin degradation products were
      detected, being highest at RDIW. This suggests that the negative impact of water
      stress and high temperature on anthocyanins results from the repression of
      biosynthesis at the onset of ripening and from degradation at later stages. On
      the other hand, berries grown under SDI displayed a higher content in phenolics
      than those under RDI, pointing out for the attenuation of the negative
      temperature effects under SDI. Irrigation regime and berry position had small
      effect on free-ABA concentration. However, ABA catabolism/conjugation process and
      ABA biosynthetic pathway were affected by water and heat stresses. This indicates
      the role of ABA-GE and catabolites in berry ABA homeostasis under abiotic
      stresses. Principal component analysis (PCA) showed that the strongest influence
      in berry ripening is the deficit irrigation regime, while temperature is an
      important variable determining the improvement or impairment of berry quality by
      the deficit irrigation regime. In summary, this work shows the interaction
      between irrigation regime and high temperature on the control of berry ripening.

PMID- 27895647
TI  - Exogenous Trehalose Treatment Enhances the Activities of Defense-Related Enzymes
      and Triggers Resistance against Downy Mildew Disease of Pearl Millet.
AB  - In recent years, diverse physiological functions of various sugars are the
      subject of investigations. Their roles in signal transduction in plant responses
      to adverse biotic and abiotic stress conditions have become apparent, and growing
      scientific evidence has indicated that disaccharides like sucrose and trehalose
      mediate plant defense responses in similar way as those induced by elicitors
      against the pathogens. Trehalose is a well-known metabolic osmoregulator, stress
      protectant and non-reducing disaccharide existing in a variety of organisms,
      including fungi, bacteria, and plants. Commercially procured trehalose was
      applied to seeds of susceptible pearl millet (Pennisetum glaucum) cultivar "HB3,"
      and tested for its ability to reduce downy mildew disease incidence by induction
      of resistance. Seed treatment with trehalose at 200 mM for 9 h recorded 70.25%
      downy mildew disease protection, followed by those with 100 and 50 mM trehalose
      which offered 64.35 and 52.55% defense, respectively, under greenhouse
      conditions. Furthermore, under field conditions treatment with 200 mM trehalose
      for 9 h recorded 67.25% downy mildew disease protection, and reduced the disease
      severity to 32.75% when compared with untreated control which displayed 90% of
      disease severity. Trehalose did not affect either sporangial formation or
      zoospore release from sporangia, indicating that the reduction in disease
      incidence was not due to direct inhibition but rather through induction of
      resistance responses in the host. Additionally, trehalose was shown to enhance
      the levels of polyphenol oxidase, phenylalanine ammonia lyase, and peroxidase,
      which are known as markers of both biotic and abiotic stress responses. Our study
      shows that osmoregulators like trehalose could be used to protect plants against
      pathogen attacks by seed treatment, thus offering dual benefits of biotic and
      abiotic stress tolerance.

PMID- 27895646
TI  - Manufacturing Natural Killer Cells as Medicinal Products.
AB  - Natural Killer (NK) cells are innate lymphoid cells (ILC) with cytotoxic and
      regulatory properties. Their functions are tightly regulated by an array of
      inhibitory and activating receptors, and their mechanisms of activation strongly
      differ from antigen recognition in the context of human leukocyte antigen
      presentation as needed for T-cell activation. NK cells thus offer unique
      opportunities for new and improved therapeutic manipulation, either in vivo or in
      vitro, in a variety of human diseases, including cancers. NK cell activity can
      possibly be modulated in vivo through direct or indirect actions exerted by small
      molecules or monoclonal antibodies. NK cells can also be adoptively transferred
      following more or less substantial modifications through cell and gene
      manufacturing, in order to empower them with new or improved functions and ensure
      their controlled persistence and activity in the recipient. In the present
      review, we will focus on the technological and regulatory challenges of NK cell
      manufacturing and discuss conditions in which these innovative cellular therapies
      can be brought to the clinic.

PMID- 27895649
TI  - 'Omics' and Plant Responses to Botrytis cinerea.
AB  - Botrytis cinerea is a dangerous plant pathogenic fungus with wide host ranges.
      This aggressive pathogen uses multiple weapons to invade and cause serious
      damages on its host plants. The continuing efforts of how to solve the "puzzle"
      of the multigenic nature of B. cinerea's pathogenesis and plant defense
      mechanisms against the disease caused by this mold, the integration of omic
      approaches, including genomics, transcriptomics, proteomics and metabolomics,
      along with functional analysis could be a potential solution. Omic studies will
      provide a foundation for development of genetic manipulation and breeding
      programs that will eventually lead to crop improvement and protection. In this
      mini-review, we will highlight the current progresses in research in plant stress
      responses to B. cinerea using high-throughput omic technologies. We also discuss
      the opportunities that omic technologies can provide to research on B. cinerea
      plant interactions as an example showing the impacts of omics on agricultural
      research.

PMID- 27895645
TI  - Inflamm-Aging of Hematopoiesis, Hematopoietic Stem Cells, and the Bone Marrow
      Microenvironment.
AB  - All hematopoietic and immune cells are continuously generated by hematopoietic
      stem cells (HSCs) and hematopoietic progenitor cells (HPCs) through highly
      organized process of stepwise lineage commitment. In the steady state, HSCs are
      mostly quiescent, while HPCs are actively proliferating and contributing to daily
      hematopoiesis. In response to hematopoietic challenges, e.g., life-threatening
      blood loss, infection, and inflammation, HSCs can be activated to proliferate and
      engage in blood formation. The HSC activation induced by hematopoietic demand is
      mediated by direct or indirect sensing mechanisms involving pattern recognition
      receptors or cytokine/chemokine receptors. In contrast to the hematopoietic
      challenges with obvious clinical symptoms, how the aging process, which involves
      low-grade chronic inflammation, impacts hematopoiesis remains undefined. Herein,
      we summarize recent findings pertaining to functional alternations of
      hematopoiesis, HSCs, and the bone marrow (BM) microenvironment during the
      processes of aging and inflammation and highlight some common cellular and
      molecular changes during the processes that influence hematopoiesis and its cells
      of origin, HSCs and HPCs, as well as the BM microenvironment. We also discuss how
      age-dependent alterations of the immune system lead to subclinical inflammatory
      states and how inflammatory signaling might be involved in hematopoietic aging.
      Our aim is to present evidence supporting the concept of "Inflamm-Aging," or
      inflammation-associated aging of hematopoiesis.

PMID- 27895650
TI  - A Detailed Analysis of the BR1 Locus Suggests a New Mechanism for Bolting after
      Winter in Sugar Beet (Beta vulgaris L.).
AB  - Sugar beet (Beta vulgaris ssp. vulgaris) is a biennial, sucrose-storing plant,
      which is mainly cultivated as a spring crop and harvested in the vegetative stage
      before winter. For increasing beet yield, over-winter cultivation would be
      advantageous. However, bolting is induced after winter and drastically reduces
      yield. Thus, post-winter bolting control is essential for winter beet
      cultivation. To identify genetic factors controlling bolting after winter, a F2
      population was previously developed by crossing the sugar beet accessions BETA
      1773 with reduced bolting tendency and 93161P with complete bolting after winter.
      For a mapping-by-sequencing analysis, pools of 26 bolting-resistant and 297
      bolting F2 plants were used. Thereby, a single continuous homozygous region of
      103 kb was co-localized to the previously published BR1 QTL for post-winter
      bolting resistance (Pfeiffer et al., 2014). The BR1 locus was narrowed down to 11
      candidate genes from which a homolog of the Arabidopsis CLEAVAGE AND
      POLYADENYLATION SPECIFICITY FACTOR 73-I (CPSF73-I) was identified as the most
      promising candidate. A 2 bp deletion within the BETA 1773 allele of BvCPSF73-Ia
      results in a truncated protein. However, the null allele of BvCPSF73-Ia might
      partially be compensated by a second BvCPSF73-Ib gene. This gene is located 954
      bp upstream of BvCPSF73-Ia and could be responsible for the incomplete penetrance
      of the post-winter bolting resistance allele of BETA 1773. This result is an
      important milestone for breeding winter beets with complete bolting resistance
      after winter.

PMID- 27895651
TI  - Invertebrate Biosecurity Challenges in High-Productivity Grassland: The New
      Zealand Example.
AB  - To protect productive grasslands from pests and diseases, effective pre- and at
      border planning and interventions are necessary. Biosecurity failure inevitably
      requires expensive and difficult eradication, or long-term and often quite
      ineffective management strategies. This is compared to the early intervention
      more likely for sectors where there is public and political interest in plants of
      immediate economic and/or social value, and where associated pests are typically
      located above-ground on host plantings of relatively limited distribution. Here,
      biosecurity surveillance and responses can be readily designed. In contrast,
      pastures comprising plants of low inherent unit value create little, if any,
      esthetic interest. Yet, given the vast extent of pasture in New Zealand and the
      value of the associated industries, these plants are of immense economic
      importance. Compounding this is the invasibility of New Zealand's pastoral
      ecosystems through a lack of biotic resistance to incursion and invasion.
      Further, given the sheer area of pasture, intervention options are limited
      because of costs per unit area and the potential for pollution if pesticides are
      used. Biosecurity risk for pastoral products differs from, say, that of fruit
      where at least part of an invasive pathway can be recognized and risks assessed.
      The ability to do this via pastoral sector pathways is much reduced, since risk
      organisms more frequently arrive via hitchhiker pathways which are diffuse and
      varied. Added to this pasture pests within grassland ecosystems are typically
      cryptic, often with subterranean larval stages. Such characteristics make
      detection and response particularly difficult. The consequences of this threaten
      to add to the already-increasing stressors of production intensification and
      climate change. This review explores the unique challenges faced by pasture
      biosecurity and what may be done to confront existing difficulties. While there
      is no silver bullet, and limited opportunity pre- and at-border for improving
      pasture biosecurity, advancement may include increased and informed vigilance by
      farmers, pheromone traps and resistant plants to slow invasion. Increasingly,
      there is also the potential for more use of improved population dispersal models
      and surveillance strategies including unmanned aerial vehicles, as well as
      emerging techniques to determine invasive pest genomes and their geographical
      origins.

PMID- 27895644
TI  - Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications.
AB  - Allogeneic hematopoietic stem cell transplantation is associated with serious
      complications, and improvement of the overall clinical outcome of patients with
      hematological malignancies is necessary. During the last decades, posttransplant
      donor-derived adoptive cellular immunotherapeutic strategies have been
      progressively developed for the treatment of graft-versus-host disease (GvHD),
      infectious complications, and tumor relapses. To date, the common challenge of
      all these cell-based approaches is their implementation for clinical application.
      Establishing an appropriate manufacturing process, to guarantee safe and
      effective therapeutics with simultaneous consideration of economic requirements
      is one of the most critical hurdles. In this review, we will discuss the recent
      scientific findings, clinical experiences, and technological advances for cell
      processing toward the application of mesenchymal stromal cells as a therapy for
      treatment of severe GvHD, virus-specific T cells for targeting life-threating
      infections, and of chimeric antigen receptors-engineered T cells to treat
      relapsed leukemia.

PMID- 27895652
TI  - Rapid Evolution of Manifold CRISPR Systems for Plant Genome Editing.
AB  - Advanced CRISPR-Cas9 based technologies first validated in mammalian cell systems
      are quickly being adapted for use in plants. These new technologies increase
      CRISPR-Cas9's utility and effectiveness by diversifying cellular capabilities
      through expression construct system evolution and enzyme orthogonality, as well
      as enhanced efficiency through delivery and expression mechanisms. Here, we
      review the current state of advanced CRISPR-Cas9 and Cpf1 capabilities in plants
      and cover the rapid evolution of these tools from first generation inducers of
      double strand breaks for basic genetic manipulations to second and third
      generation multiplexed systems with myriad functionalities, capabilities, and
      specialized applications. We offer perspective on how to utilize these tools for
      currently untested research endeavors and analyze strengths and weaknesses of
      novel CRISPR systems in plants. Advanced CRISPR functionalities and delivery
      options demonstrated in plants are primarily reviewed but new technologies just
      coming to the forefront of CRISPR development, or those on the horizon, are
      briefly discussed. Topics covered are focused on the expansion of expression and
      delivery capabilities for CRISPR-Cas9 components and broadening targeting range
      through orthogonal Cas9 and Cpf1 proteins.

PMID- 27895654
TI  - A Comprehensive Phylogeny Reveals Functional Conservation of the UV-B
      Photoreceptor UVR8 from Green Algae to Higher Plants.
AB  - Ultraviolet-B (UV-B) is present in sunlight (280-315 nm) and has diverse effects
      on living organisms. Low fluence rate of exposure induces a specific
      photomorphogenic response regulated by the UV-B response locus 8 (UVR8) receptor.
      UVR8 was first described in Arabidopsis thaliana. In the absence of stimuli it is
      located in the cytoplasm as a homodimer. However, upon UV-B irradiation, it
      switches to a monomer and interacts with the ubiquitin ligase E3 COP1 via the
      UVR8 beta-propeller domain and the VP core. This induces the expression of the
      transcription factor HY5 leading to changes in the expression of genes associated
      with UV-B acclimation and stress tolerance. UVR8 senses UV-B through tryptophan
      residues being Trp233 and 285 the most important. Based on the comparison and
      analysis of UVR8 functionally important motifs, we report a comprehensive
      phylogeny of UVR8, trying to identify UVR8 homologs and the ancestral organism
      where this gene could be originated. Results obtained showed that Chlorophytes
      are the first organisms from the Viridiplantae group where UVR8 appears. UVR8 is
      present in green algae, bryophytes, lycophytes, and angiosperms. All the
      sequences identified contain tryptophans 233 and 285, arginines involved in
      homodimerization and the VP domain suggesting they are true UVR8 photoreceptors.
      We also determined that some species from bryophytes and angiosperms contain more
      than one UVR8 gene copy posing the question if UVR8 could constitute a gene
      family in these species. In conclusion, we described the functional conservation
      among UVR8 proteins from green algae to higher plants.

PMID- 27895653
TI  - Genome-Wide Identification and Expression Analysis of the Tubby-Like Protein
      Family in the Malus domestica Genome.
AB  - Tubby-like proteins (TLPs), which have a highly conserved beta barrel tubby
      domain, have been found to be associated with some animal-specific
      characteristics. In the plant kingdom, more than 10 TLP family members were
      identified in Arabidopsis, rice and maize, and they were found to be involved in
      responses to stress. The publication of the apple genome makes it feasible to
      systematically study the TLP family in apple. In this investigation, nine TLP
      encoding genes (TLPs for short) were identified. When combined with the TLPs from
      other plant species, the TLPs were divided into three groups (group A, B, and C).
      Most plant TLP members in group A contained an additional F-box domain at the N
      terminus. However, no common domain was identified other than tubby domain either
      in group B or in group C. An analysis of the tubby domains of MdTLPs identified
      three types of conserved motifs. Motif 1 and 2, the signature motifs in the
      confirmed TLPs, were always present in MdTLPs, while motif 3 was absent from
      group B. Homology modeling indicated that the tubby domain of most MdTLPs had a
      closed beta barrel, as in animal tubby domains. Expression profiling revealed
      that the MdTLP genes were expressed in multiple organs and were abundant in
      roots, stems, and leaves but low in flowers. An analysis of cis-acting elements
      showed that elements related to the stress response were prevalent in the
      promoter sequences of MdTLPs. Expression profiling by qRT-PCR indicated that
      almost all MdTLPs were up-regulated at some extent under abiotic stress,
      exogenous ABA and H2O2 treatments in leaves and roots, though different MdTLP
      members exhibited differently in leaves and roots. The results and information
      above may provide a basis for further investigation of TLP function in plants.

PMID- 27895655
TI  - Protein Tyrosine Nitration during Development and Abiotic Stress Response in
      Plants.
AB  - In recent years, the study of nitric oxide (NO) in plant systems has attracted
      the attention of many researchers. A growing number of investigations have shown
      the significance of NO as a signal molecule or as a molecule involved in the
      response against (a)biotic processes. NO can be responsible of the post
      translational modifications (NO-PTM) of target proteins by mechanisms such as the
      nitration of tyrosine residues. The study of protein tyrosine nitration during
      development and under biotic and adverse environmental conditions has increased
      in the last decade; nevertheless, there is also an endogenous nitration which
      seems to have regulatory functions. Moreover, the advance in proteome techniques
      has enabled the identification of new nitrated proteins, showing the high
      variability among plant organs, development stage and species. Finally, it may be
      important to discern between a widespread protein nitration because of greater
      RNS content, and the specific nitration of key targets which could affect cell
      signaling processes. In view of the above point, we present a mini-review that
      offers an update about the endogenous protein tyrosine nitration, during plant
      development and under several abiotic stress conditions.

PMID- 27895656
TI  - Meselect - A Rapid and Effective Method for the Separation of the Main Leaf
      Tissue Types.
AB  - Individual tissues of complex eukaryotic organisms have specific gene expression
      programs that control their functions. Therefore, tissue-specific molecular
      information is required to increase our understanding of tissue-specific
      processes. Established methods in plants to obtain specific tissues or cell types
      from their organ or tissue context typically require the enzymatic degradation of
      cell walls followed by fluorescence-activated cell sorting (FACS) using plants
      engineered for localized expression of green fluorescent protein. This has
      facilitated the acquisition of valuable data, mainly on root cell type-specific
      transcript and protein expression. However, FACS of different leaf cell types is
      difficult because of chlorophyll autofluorescence that interferes with the
      sorting process. Furthermore, the cell wall composition is different in each cell
      type. This results in long incubation times for refractory cell types, and cell
      sorting itself can take several hours. To overcome these limitations, we
      developed Meselect (mechanical separation of leaf compound tissues), a rapid and
      effective method for the separation of leaf epidermal, vascular and mesophyll
      tissues. Meselect is a novel combination of mechanical separation and rapid
      protoplasting, which benefits from the unique cell wall composition of the
      different tissue types. Meselect has several advantages over cell sorting: it
      does not require expensive equipment such as a cell sorter and does not depend on
      specific fluorescent reporter lines, the use of blenders as well as the inherent
      mixing of different cell types and of intact and damaged cells can be avoided,
      and the time between wounding of the leaf and freezing of the sample is short.
      The efficacy and specificity of the method to enrich the different leaf tissue
      types has been confirmed using Arabidopsis leaves, but it has also been
      successfully used for leaves of other plants such as tomato or cassava. The
      method is therefore useful for plant scientists investigating leaf development or
      responses to stimuli at the tissue-specific level.

PMID- 27895657
TI  - Implication of the Whitefly Bemisia tabaci Cyclophilin B Protein in the
      Transmission of Tomato yellow leaf curl virus.
AB  - Tomato yellow leaf curl virus (TYLCV) is a single-stranded (ssDNA) begomoviruses
      that causes severe damage to tomato and several other crops worldwide. TYLCV is
      exclusively transmitted by the sweetpotato whitefly, Bemisia tabaci in a
      persistent circulative and propagative manner. Previous studies have shown that
      the transmission, retention, and circulation of TYLCV in its vector involves
      interaction with insect and endosymbiont proteins, which aid in the transmission
      of the virus, or have a protective role in response to the presence of the virus
      in the insect body. However, only a low number of such proteins have been
      identified. Here, the role of B. tabaci Cyclophilin B (CypB) in the transmission
      of TYLCV protein was investigated. Cyclophilins are a large family of cellular
      prolyl isomerases that have many molecular roles including facilitating protein
      protein interactions in the cell. One cyclophilin protein has been implicated in
      aphid-luteovirus interactions. We demonstrate that the expression of CypB from B.
      tabaci is altered upon TYLCV acquisition and retention. Further experiments used
      immunocapture-PCR and co-immunolocalization and demonstrated a specific
      interaction and colocalization between CypB and TYLCV in the the midgut, eggs,
      and salivary glands. Membrane feeding of anti-CypB antibodies and TYLCV-infected
      plants showed a decrease in TYLCV transmission, suggesting a critical role that
      CypB plays in TYLCV transmission. Further experiments, which used membrane
      feeding with the CypB inhibitor Cyclosporin A showed decrease in CypB-TYLCV
      colocalization in the midgut and virus transmission. Altogether, our results
      indicate that CypB plays an important role in TYLCV transmission by B. tabaci.

PMID- 27895658
TI  - Overexpression of a Hevea brasiliensis ErbB-3 Binding protein 1 Gene Increases
      Drought Tolerance and Organ Size in Arabidopsis.
AB  - Rubber trees are economically important tropical tree species and the major
      source of natural rubber, which is an essential industrial material. This
      tropical perennial tree is susceptible to cold stress and other abiotic stresses,
      especially in the marginal northern tropics. Recent years, the genome sequencing
      and RNA-seq projects produced huge amount of sequence data, which greatly
      facilitated the functional genomics study. However, the characterization of
      individual functional gene is in urgent demands, especially for those involved in
      stress resistance. Here we identified and characterized the rubber tree gene ErbB
      3 binding protein 1, which undergoes changes in expression in response to cold,
      drought stress and ABA treatment. HbEBP1 overexpression (OE) in Arabidopsis
      increased organ size, facilitated root growth and increased adult leaf number by
      delaying the vegetative-to-reproductive transition. In addition, HbEBP1 OE
      enhanced the resistance of the Arabidopsis plants to freezing and drought stress,
      demonstrating that this gene participates in the regulation of abiotic stress
      resistance. RD29a, RD22 and CYCD3;1 expression was also greatly enhanced by
      HbEBP1 OE, which explains its regulatory roles in organ size and stress
      resistance. The regulation of drought stress resistance is a novel function
      identified in plant EBP1 genes, which expands our understanding of the roles of
      EBP1 gene in response to the environment. Our results provide information that
      may lead to the use of HbEBP1 in genetically engineered crops to increase both
      biomass and abiotic stress resistance.

PMID- 27895659
TI  - HbMADS4, a MADS-box Transcription Factor from Hevea brasiliensis, Negatively
      Regulates HbSRPP.
AB  - In plants MADS-box transcription factors (TFs) play important roles in growth and
      development. However, no plant MADS-box gene has been identified to have a
      function related to secondary metabolites regulation. Here, a MADS-box TF gene,
      designated as HbMADS4, was isolated from Hevea brasiliensis by the yeast one
      hybrid experiment to screen the latex cDNA library using the promoter of the gene
      encoding H. brasiliensis small rubber particle protein (HbSRPP) as bait. HbMADS4
      was 984-bp containing 633-bp open reading frame encoding a deduced protein of 230
      amino acid residues with a typical conserved MADS-box motif at the N terminus.
      HbMADS4 was preferentially expressed in the latex, but little expression was
      detected in the leaves, flowers, and roots. Its expression was inducible by
      methyl jasmonate and ethylene. Furthermore, transient over-expression and over
      expression of HbMADS4 in transgenic tobacco plants significantly suppressed the
      activity of the HbSRP promoter. Altogether, it is proposed that HbMADS4 is a
      negative regulator of HbSRPP which participates in the biosynthesis of natural
      rubber.

PMID- 27895660
TI  - ALA-Induced Flavonols Accumulation in Guard Cells Is Involved in Scavenging H2O2
      and Inhibiting Stomatal Closure in Arabidopsis Cotyledons.
AB  - 5-aminolevulinic acid (ALA), a new plant growth regulator, can inhibit stomatal
      closure by reducing H2O2 accumulation in guard cells. Flavonols are a main kind
      of flavonoids and have been proposed as H2O2 scavengers in guard cells. 5
      aminolevulinic acid can significantly improve flavonoids accumulation in plants.
      However, whether ALA increases flavonols content in guard cells and the role of
      flavonols in ALA-regulated stomatal movement remains unclear. In this study, we
      first demonstrated that ALA pretreatment inhibited ABA-induced stomatal closure
      by reducing H2O2 accumulation in guard cells of Arabidopsis seedlings. This
      result confirms the inhibitory effect of ALA on stomatal closure and the
      important role of decreased H2O2 accumulation in this process. We also found that
      ALA significantly improved flavonols accumulation in guard cells using a flavonol
      specific dye. Furthermore, using exogenous quercetin and kaempferol, two major
      components of flavonols in Arabidopsis leaves, we showed that flavonols
      accumulation inhibited ABA-induced stomatal movement by suppressing H2O2 in guard
      cells. Finally, we showed that the inhibitory effect of ALA on ABA-induced
      stomatal closure was largely impaired in flavonoid-deficient transparent testa4
      (tt4) mutant. In addition, exogenous flavonols recovered stomatal responses of
      tt4 to the wild-type levels. Taken together, we conclude that ALA-induced
      flavonol accumulation in guard cells is partially involved in the inhibitory
      effect of ALA on ABA-induced H2O2 accumulation and stomatal closure. Our data
      provide direct evidence that ALA can regulate stomatal movement by improving
      flavonols accumulation, revealing new insights into guard cell signaling.

PMID- 27895661
TI  - The Genome Conformation As an Integrator of Multi-Omic Data: The Example of
      Damage Spreading in Cancer.
AB  - Publicly available multi-omic databases, in particular if associated with medical
      annotations, are rich resources with the potential to lead a rapid transition
      from high-throughput molecular biology experiments to better clinical outcomes
      for patients. In this work, we propose a model for multi-omic data integration
      (i.e., genetic variations, gene expression, genome conformation, and epigenetic
      patterns), which exploits a multi-layer network approach to analyse, visualize,
      and obtain insights from such biological information, in order to use achieved
      results at a macroscopic level. Using this representation, we can describe how
      driver and passenger mutations accumulate during the development of diseases
      providing, for example, a tool able to characterize the evolution of cancer.
      Indeed, our test case concerns the MCF-7 breast cancer cell line, before and
      after the stimulation with estrogen, since many datasets are available for this
      case study. In particular, the integration of data about cancer mutations, gene
      functional annotations, genome conformation, epigenetic patterns, gene
      expression, and metabolic pathways in our multi-layer representation will allow a
      better interpretation of the mechanisms behind a complex disease such as cancer.
      Thanks to this multi-layer approach, we focus on the interplay of chromatin
      conformation and cancer mutations in different pathways, such as metabolic
      processes, that are very important for tumor development. Working on this model,
      a variance analysis can be implemented to identify normal variations within each
      omics and to characterize, by contrast, variations that can be accounted to
      pathological samples compared to normal ones. This integrative model can be used
      to identify novel biomarkers and to provide innovative omic-based guidelines for
      treating many diseases, improving the efficacy of decision trees currently used
      in clinic.

PMID- 27895662
TI  - Muscle-Enriched MicroRNAs Isolated from Whole Blood Are Regulated by Exercise and
      Are Potential Biomarkers of Cardiorespiratory Fitness.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene
      expression post-transcriptionally. Evidence indicating miRNAs influence exercise
      induced health and performance adaptations is mounting. Circulating miRNAs are
      responsible for intercellular communication and could serve as biomarkers for
      disease and exercise-related traits. Such biomarkers would contribute to exercise
      screening, monitoring, and the development of personalized exercise prescription.
      Accordingly, we investigated the impact of long-term strenuous aerobic exercise
      training and a single bout of maximal aerobic exercise on five muscle-enriched
      miRNAs implicated in exercise adaptations (miR-1, miR-133a, miR-181a, miR-486,
      and miR-494). We also determined linear correlations between miRNAs, resting
      heart rate, and maximum oxygen uptake (O2 max). We used TaqMan assay quantitative
      polymerase chain reaction to analyze the abundance of miR-1, miR-133a, miR-181a,
      miR-486, and miR-494 in resting whole blood of 67 endurance athletes and 61
      healthy controls. Relative to controls, endurance athletes exhibited increased
      miR-1, miR-486, and miR-494 content (1.26- to 1.58-fold change, all p < 0.05).
      miR-1, miR-133a, and miR-486 were decreased immediately after maximal aerobic
      exercise (0.64- to 0.76-fold change, all p < 0.01) performed by 19 healthy, young
      men (20.7 +/- 2.4 years). Finally, we observed positive correlations between
      miRNA abundance and O2 max (miR-1 and miR-486) and an inverse correlation between
      miR-486 and resting heart rate. Therefore, muscle-enriched miRNAs isolated from
      whole blood are regulated by acute and long-term aerobic exercise training and
      could serve as biomarkers of cardiorespiratory fitness.

PMID- 27895663
TI  - MiR-30a-5p Overexpression May Overcome EGFR-Inhibitor Resistance through
      Regulating PI3K/AKT Signaling Pathway in Non-small Cell Lung Cancer Cell Lines.
AB  - Lung cancer is one of the most common deadly diseases worldwide, most of which is
      non-small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR)
      mutant NSCLCs frequently respond to the EGFR tyrosine kinase inhibitors (EGFR
      TKIs) treatment, such as Gefitinib and Erlotinib, but the development of acquired
      resistance limits the utility. Multiple resistance mechanisms have been explored,
      e.g., the activation of alternative tyrosine kinase receptors (TKRs) sharing
      similar downstream pathways to EGFR. MicroRNAs (miRNAs) are short, endogenous and
      non-coding RNA molecules, regulating the target gene expression. In this study,
      we explored the potential of miR-30a-5p in targeting the EGFR and insulin-like
      growth factor receptor-1 (IGF-1R) signaling pathways to overcome the drug
      resistance. IGF-1R is one of the tyrosine kinase receptors that share the same
      EGFR downstream molecules, including phosphatidylinositol 3 kinase (PI3K) and
      protein kinase B (AKT). In this work, an in vitro study was designed using EGFR
      inhibitor (Gefitinib), IGF-1R inhibitor (NVP-AEW541), and miRNA mimics in two
      Gefitinib-resistant NSCLC cell lines, H460 and H1975. We found that the
      combination of EGFR and IGF-1R inhibitors significantly decreased the
      phosphorylated AKT (p-AKT) expression levels compared to the control group in
      these two cell lines. Knockdown of phosphoinositide-3-kinase regulatory subunit 2
      (PIK3R2) had the same effect with the dual inhibition of EGFR and IGF-1R to
      reduce the expression of p-AKT in the signaling pathway. Overexpression of miR
      30a-5p significantly reduced the expression of the PI3K regulatory subunit
      (PIK3R2) to further induce cell apoptosis, and inhibit cell invasion and
      migration properties. Hence, miR-30a-5p may play vital roles in overcoming the
      acquired resistance to EGFR-TKIs, and provide useful information for establishing
      novel cancer treatment.

PMID- 27895665
TI  - Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in
      Mice.
AB  - In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain
      and results in learning deficits. Sugammadex is a new selective neuromuscular
      blockade (NMB) binding agent that anesthesiologists can use to achieve immediate
      reversal of an NMB with few side effects. Given its molecular weight of 2178,
      sugammadex is thought to be unable to pass through the blood brain barrier (BBB).
      Volatile anesthetics can influence BBB opening and integrity. Therefore, we
      investigated whether the intraperitoneal administration of sugammadex could
      exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes
      in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis,
      and the ultrastructure of the BBB was examined by transmission electron
      microscopy. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural
      abnormalities in the hippocampus of neonatal mice. Sugammadex alone without
      sevoflurane did not induce apoptosis. The coadministration of sugammadex with
      sevoflurane to neonatal mice caused a significant increase (150%) in
      neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia,
      sugammadex could influence neurotoxicity together with sevoflurane. Exposure to
      2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the
      hippocampus of neonatal mice.

PMID- 27895667
TI  - Attitude to the Menopause and Sex amongst Middle-Aged Women in a Family Medicine
      Clinic in Ibadan, Nigeria.
AB  - Background. Menopause is the expected end of reproductive life. Having a positive
      attitude towards it has been shown to result in a positive experience, while a
      negative attitude is associated with negative experiences and symptoms.
      Traditionally, women often abstain from sex after menopause. The study aimed to
      determine the level of awareness and perceptions about the menopause and sex in
      perimenopausal women attending a general outpatient clinic. Methods. Women over
      40 years were recruited from the Family Medicine Department of University College
      Hospital, excluding those who were menopausal. Data analyses were done with chi
      square test (p < 0.05). Results. Most (302; 86.4%) of the 352 surveyed
      participants were aware of the menopause. Only 36.1% anticipated associated
      symptoms. About half (55.7%) were indifferent to menopause onset, while 23% had a
      positive attitude and 21.4% had a negative attitude, respectively. Younger women
      were less likely to have a positive attitude to the menopause (p = 0.04). There
      were negative cultural beliefs towards sex. Sexual activity was low and declined
      with age (p < 0.001). Many women would like treatment to improve their sexual
      activity. Conclusion. Most participants had a favourable disposition towards the
      menopause, though sexual relationships suffer. Counselling and treatment should
      be offered.

PMID- 27895668
TI  - Oral Tuberculosis: A Rare Manifestation of Disseminated Disease in a Patient with
      Dermatomyositis on Chronic Corticosteroids.
AB  - Tuberculosis remains one of the leading causes of death around the world despite
      advancements in diagnostic testing and medical therapies. It commonly affects the
      lungs, but isolated extra pulmonary clinical manifestations have been reported.
      Tuberculosis of the oral cavity is exceedingly rare. We present a case of a
      patient with dermatomyositis on chronic steroid therapy, who presented with
      tuberculosis involving the tongue as the only clinical manifestation of
      disseminated disease. Physicians must be aware of extra pulmonary manifestations
      of tuberculosis in patients at risk, in order to avoid delays in diagnosis and
      treatment and to prevent further contagion.

PMID- 27895669
TI  - Myeloproliferative Disease: An Unusual Cause of Raynaud's Phenomenon and Digital
      Ischaemia.
AB  - We describe a 59-year-old female who presented with ischaemic digits, preceded by
      a 6-month history of Raynaud's phenomenon affecting her fingers and toes. There
      were no clinical or laboratory features of primary vasculitis or connective
      tissue disease, Doppler imaging was normal, and bloods were unremarkable aside
      from a platelet count of 786 * 109/L (150-400) and white cells of 16 * 109/L (4
      11). In view of the thrombocytosis a JAK2 mutation assay was requested which
      confirmed a JAK2 V617F mutation, suggesting essential thrombocytosis (ET) as the
      cause. She received treatment with hydroxycarbamide which normalised her platelet
      count and led to a complete resolution of her Raynaud's symptoms. Raynaud's
      phenomenon is a rare manifestation of ET. Myeloproliferative disorders such as ET
      should be considered in the differential diagnosis of Raynaud's phenomenon and
      vasculitis.

PMID- 27895666
TI  - Cardiometabolic Risk in Hyperlipidemic Men and Women.
AB  - Objective. The aim of this study was to evaluate sex specific differences of
      metabolic and clinical characteristics of treated hyperlipidemic men and women
      (HL-men and HL-women). Methods. In this study vascular and metabolic
      characteristics of 35 HL-women and 64 HL-men were assessed. In addition a sex
      specific analysis of metabolic and nutritional habits of HL-patients with
      prediabetes (HL-IGR) was done. Results. HL-women were older and had favourable
      concentrations of high density lipoprotein cholesterol (HDL-cholesterol),
      triglycerides (TG), and triglyceride/HDL-cholesterol ratio (TG/HDL-ratio) but
      were also shown to have higher concentrations of lipoprotein-a compared to HL
      men. HL-men were characterized as having higher levels of liver-specific
      parameters and body weight as well as being more physically active compared to HL
      women. Brain natriuretic peptide (pro-BNP) was higher in HL-women than HL-men,
      while no differences in metabolic syndrome and glycemic parameters were shown. HL
      IGR-women were also older and still had a better profile of sex specific lipid
      parameters, as well as a lower body weight compared to HL-IGR-men. No differences
      were seen in vascular parameters such as the intima media thickness (IMT).
      Conclusion. HL-women were older and had overall more favourable concentrations of
      lipid parameters and liver enzymes but did not differ regarding vascular
      morphology and insulin sensitivity compared to HL-men of comparable body mass
      index (BMI).

PMID- 27895664
TI  - Application of Genomic Technologies to the Breeding of Trees.
AB  - The recent introduction of next generation sequencing (NGS) technologies
      represents a major revolution in providing new tools for identifying the genes
      and/or genomic intervals controlling important traits for selection in breeding
      programs. In perennial fruit trees with long generation times and large sizes of
      adult plants, the impact of these techniques is even more important. High
      throughput DNA sequencing technologies have provided complete annotated sequences
      in many important tree species. Most of the high-throughput genotyping platforms
      described are being used for studies of genetic diversity and population
      structure. Dissection of complex traits became possible through the availability
      of genome sequences along with phenotypic variation data, which allow to
      elucidate the causative genetic differences that give rise to observed phenotypic
      variation. Association mapping facilitates the association between genetic
      markers and phenotype in unstructured and complex populations, identifying
      molecular markers for assisted selection and breeding. Also, genomic data provide
      in silico identification and characterization of genes and gene families related
      to important traits, enabling new tools for molecular marker assisted selection
      in tree breeding. Deep sequencing of transcriptomes is also a powerful tool for
      the analysis of precise expression levels of each gene in a sample. It consists
      in quantifying short cDNA reads, obtained by NGS technologies, in order to
      compare the entire transcriptomes between genotypes and environmental conditions.
      The miRNAs are non-coding short RNAs involved in the regulation of different
      physiological processes, which can be identified by high-throughput sequencing of
      RNA libraries obtained by reverse transcription of purified short RNAs, and by in
      silico comparison with known miRNAs from other species. All together, NGS
      techniques and their applications have increased the resources for plant breeding
      in tree species, closing the former gap of genetic tools between trees and annual
      species.

PMID- 27895671
TI  - Long term results of PDR brachytherapy for lip cancer.
AB  - PURPOSE: To evaluate the long time outcome with regard to local tumour control
      and side effects of a pulsed dose rate (PDR) monobrachytherapy of primary or
      recurrent cancer of the lip. MATERIAL AND METHODS: Between 1995 and 2007 we
      treated 43 patients with primary or recurrent clinical T1-T3N0 lip cancers. There
      were 22 T1 patients (51%), 16 T2 (37%) and 5 T3 cases (12%). A median dose of 60
      (55-66) Gy was given, depending on the tumour volume. The PDR treatment was
      delivered with 0.83 Gy/pulse every second hour for 5.5-6.5 days. The patients
      were followed for a median of 55 (1-158) months. RESULTS: The 2-, 5- and 10-year
      rates of actuarial local control were 97.6%, 94.5% and 94.5%, overall survival
      88.0%, 58.9% and 39.1%, disease free survival 92.7%, 86.4% and 86.4%
      respectively. The regional control rate was 93%. One patient (2%) developed
      distant metastases. A dosimetrical analysis showed a mean treated volume of 14.9
      (3.0-56.2) cm3. Long-term side effects were mild and the cosmetic outcome
      excellent, except for 1 case (2%) of soft tissue necrosis and 1 case (2%) of
      osteoradionecrosis. CONCLUSIONS: Local outcome is excellent and similar to other
      published studies of continuous low dose rate (cLDR) brachytherapy.

PMID- 27895670
TI  - Wnt5a Increases Properties of Lung Cancer Stem Cells and Resistance to Cisplatin
      through Activation of Wnt5a/PKC Signaling Pathway.
AB  - The development of chemoresistance to cisplatin regimens causes a poor prognosis
      in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the
      regulation of properties of lung cancer stem cells and chemoresistance was
      interrogated, by accessing capacities of cell proliferation, migration, invasion,
      and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin
      resistant A549 cells treated with Wnt5a conditional medium or protein kinase C
      (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling
      ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony
      formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP
      cells and increase the fraction of ALDH-positive cell in A549/DDP cells. An
      exposure of cells to Wnt5a led to a significant reduction of A549/DDP cell
      apoptosis but not A549 cells. An addition of GF109203X could both strikingly
      increase the baseline apoptosis and resensitize the Wnt5a-inhibited cell
      apoptosis. Interestingly, an inhibition of Wnt/PKC signaling pathway could reduce
      properties of lung cancer stem cells, promote cell apoptosis, and resensitize
      cisplatin-resistant cells to cisplatin via a caspase/AIF-dependent pathway. These
      data thus suggested that the Wnt5a could promote lung cancer cell mobility and
      cisplatin-resistance through a Wnt/PKC signaling pathway and a blockage of this
      signaling may be an alternative therapeutic strategy for NSCLC patients with
      resistance to chemotherapies.

PMID- 27895672
TI  - Preoperative high dose rate brachytherapy for clinical stage II endometrial
      carcinoma.
AB  - PURPOSE: We sought to evaluate pathological response, tolerance, and outcome
      after preoperative (neoadjuvant) high dose rate brachytherapy in a small series
      of patients with clinical stage II endometrial carcinoma, and to evaluate a dose
      and fractionation protocol for this treatment. MATERIAL AND METHODS: Twelve women
      diagnosed with clinical stage II endometrial carcinoma from 1999-2010 were
      treated with preoperative radiation therapy. Their medical charts were
      retrospectively analyzed for HDR treatment regimen, pathological response, and
      longitudinal outcomes. Radiation doses were normalized to a biologically
      equivalent dose of 2 Gy per fraction (EQD2). RESULTS: Two patients had complete
      pathological response to neoadjuvant therapy; five more had only microscopic
      residual disease at the time of surgery. At a median follow up of 37 months (1-91
      months), one patient has developed recurrence at the vaginal apex six months
      after completing initial therapy, while another developed a lung recurrence at 28
      months. Two-year disease-free and cause-specific survivals were 88% and 100%,
      respectively. CONCLUSIONS: Our small study shows that the HDR fractionation
      schedule, as done in our series for preoperative radiation therapy for clinical
      stage II endometrial cancer, is well tolerated and would be an option for
      patients treated with neoadjuvant radiation therapy.

PMID- 27895673
TI  - Radiobiologically based treatment plan evaluation for prostate seed implants.
AB  - PURPOSE: Accurate prostate low dose-rate brachytherapy treatment plan evaluation
      is important for future care decisions. Presently, an evaluation is based on
      dosimetric quantifiers for the tumor and organs at risk. However, these do not
      account for effects of varying dose-rate, tumor repopulation and other biological
      effects. In this work, incorporation of the biological response is used to obtain
      more clinically relevant treatment plan evaluation. MATERIAL AND METHODS: Eleven
      patients were evaluated. Each patient received a 145 Gy implant. Iodine-125 seeds
      were used and the treatment plans were created on the Prowess system. Based on CT
      images the post-implant plan was created. In the post-plan, the tumor, urethra,
      bladder and rectum were contoured. The biologically effective dose was used to
      determine the tumor control probability and the normal tissue complication
      probabilities for the urethra, bladder, rectum and surrounding tissue. RESULTS:
      The average tumor control probability and complication probabilities for the
      urethra, bladder, rectum and surrounding tissue were 99%, 29%, 0%, 12% and 6%,
      respectively. These measures provide a simpler means for evaluation and since
      they include radiobiological factors, they provide more reliable estimation of
      the treatment outcome. CONCLUSIONS: The goal of this work was to create more
      clinically relevant prostate seed-implant evaluation by incorporating
      radiobiological measures. This resulted in a simpler descriptor of treatment plan
      quality and was consistent with patient outcomes.

PMID- 27895674
TI  - Perioperative high dose rate (HDR) brachytherapy in unresectable locally advanced
      pancreatic tumors.
AB  - PURPOSE: The aim of the study was to present an original technique of catheter
      implantation for perioperative HDR-Ir192 brachytherapy in patients after
      palliative operations of unresectable locally advanced pancreatic tumors and to
      estimate the influence of perioperative HDR-Ir192 brachytherapy on pain relief in
      terminal pancreatic cancer patients. MATERIAL AND METHODS: Eight patients with
      pancreatic tumors located in the head of pancreas underwent palliative operations
      with the use of HDR-Ir192 brachytherapy. All patients qualified for surgery
      reported pain of high intensity and had received narcotic painkillers prior to
      operation. During the last phase of the surgery, the Nucletron(r) catheters were
      implanted in patients to prepare them for later perioperative brachytherapy.
      Since the 6th day after surgery HDR brachytherapy was performed. Before each
      brachytherapy fraction the location of implants were checked using fluoroscopy. A
      fractional dose was 5 Gy and a total dose was 20 Gy in the area of radiation. A
      comparative study of two groups of patients (with and without brachytherapy) with
      stage III pancreatic cancer according to the TNM scale was taken in
      consideration. RESULTS AND CONCLUSIONS: The authors claim that the modification
      of catheter implantation using specially designed cannula, facilitates the
      process of inserting the catheter into the tumor, shortens the time needed for
      the procedure, and reduces the risk of complications. Mean survival time was 5.7
      months. In the group of performed brachytherapy, the mean survival time was 6.7
      months, while in the group of no brachytherapy performed - 4.4 months. In the
      group of brachytherapy, only one patient increased the dose of painkillers in the
      last month of his life. Remaining patients took constant doses of medicines.
      Perioperative HDR-Ir192 brachytherapy could be considered as a practical
      application of adjuvant therapy for pain relief in patients with an advanced
      pancreatic cancer.

PMID- 27895675
TI  - BiopSee(r) - transperineal stereotactic navigated prostate biopsy.
AB  - In the recent years, prostate cancer was the most commonly diagnosed cancer in
      men. Currently secure diagnosis confirmation is done by a transrectal biopsy and
      following histopathological examination. Conventional transrectal biopsy success
      rates are rather low with ca. 30% detection upon the first and ca 20% after re
      biopsy. The paper presents a novel system for stereotactic navigated prostate
      biopsy. The approach results into higher accuracy, reproducibility and
      unrestricted and effective access to all prostate regions. Custom designed
      ultrasound, new template design and integrated 2-axes stepper allows superior 2D
      and 3D prostate imaging quality and precise needle navigation. DICOM
      functionality and image fusion enable to import pre-operative datasets (e.g.
      multiparametric MRI, targets etc.) and overlay all available radiological
      information into the biopsy planning and guiding procedure. The biopsy needle
      insertion itself is performed under augmented reality ultrasound guidance. Each
      procedure step is automatically documented in order to provide quality assurance
      and permit data re-usage for the further treatment. First clinical results
      indicates success rates of ca. 70% by first biopsies by our approach.

PMID- 27895676
TI  - A comprehensive study on HDR brachytherapy treatments of cervical cancers: using
      the first Co-60 BEBIG Multisource Unit in Bangladesh.
AB  - PURPOSE: The report presents an extraordinary synthesis of customer acceptance
      procedures (CAP), quality assurance tests (QA) in the treatment of cervical
      cancer patients, using the first Co-60 Multisource Unit(r) in Bangladesh. The QA
      and commissioning required measurements and emergency tests verifying the
      functional limits of parameters acceptable for the new HDR afterloader.
      Acceptable limits were: 1) the deviation between specified and measured source
      strength: +/- 3%; 2) the positional accuracy and uniformity: +/- 1 mm; 3) the
      temporal accuracy (i.e. timer error and linearity and end error): +/- 1% or 30
      sec.; 4) treatment planning system (digitizer and localization software): +/- 3%
      or 1 mm; 5) the distance from line to first dwell position and all the others: 5
      mm and 10 mm (+/- 1 mm). MATERIAL AND METHODS: Till February 2011, 47 patients
      were treated with HDR with more than 140 insertions applied. Amongst them, 12
      patients were in stage IIB and IIIB, 22 were postoperative (IA and IB) while the
      remaining 13 patients were with unknown stage. All the cases with stage IIB and
      IIIB received concurrent chemo-radiation and brachytherapy. Postoperative
      patients received EBRT (50 Gy and HDR) according to the institutional protocol.
      CT scans were completed before HDR-plus planning with a good reproducibility (+/-
      2%) and were documented in repeating the plan for the same set up of a patient.
      Absorbed dose (Gy) to a point P, at a distance of "r" in centimeters from a
      source of the Reference Air Kerma Rate (RAKR) has been utilized for the QA of the
      source, where source strength measurement was accomplished. RESULTS: All methods
      and analysis applicable to the QA and commissioning of Co-60 have been
      investigated and systematically analyzed, measured and documented before the
      treatment of a patient. Studies and safety requirements of this HDR remote
      afterloader were carried out. Acceptance and the QA were imperative to justify
      functionality and dependability in delivering the treatment. Implications of
      these studies were described in detail in this paper, where equipments and
      guidelines of measurement parameters are enunciated. CONCLUSIONS: We noted that
      contouring structures from CT images, prescription points for dose delivery,
      optimization, isodose evaluation, DVH, dwell times and a 3-D Dose reconstructed
      images, etc. followed by a final verification after delivering the treatment at
      the console, are well prepared in the new planning software. We present our
      material as an early preliminary report.

PMID- 27895677
TI  - Predictors of prostate volume reduction following neoadjuvant cytoreductive
      androgen suppression.
AB  - PURPOSE: Limited duration cytoreductive neoadjuvant hormonal therapy (NHT) is
      used prior to definitive radiotherapeutic management of prostate cancer to
      decrease prostate volume. The purpose of this study is to examine the effect of
      NHT on prostate volume before permanent prostate brachytherapy (PPB), and
      determine associated predictive factors. MATERIAL AND METHODS: Between June 1998
      and April 2012, a total of 1,110 patients underwent PPB and 207 patients
      underwent NHT. Of these, 189 (91.3%) underwent detailed planimetric transrectal
      ultrasound before and after NHT prior to PPB. Regression analysis was used to
      assess predictors of absolute and percentage change in prostate volume after NHT.
      RESULTS: The median duration of NHT was 4.9 months with inter quartile range
      (IQR), 4.2-6.6 months. Prostate-specific antigen (PSA) reduced by a median of 97%
      following NHT. The mean prostate volume before NHT was 62.5 +/- 22.1 cm3 (IQR: 46
      76 cm3), and after NHT, it was 37.0 +/- 14.5 cm3 (IQR: 29-47 cm3). The mean
      prostate volume reduction was 23.4 cm3 (35.9%). Absolute prostate volume
      reduction was positively correlated with initial volume and inversely correlated
      with T-stage, Gleason score, and NCCN risk group. In multivariate regression
      analyses, initial prostate volume (p < 0.001) remained as a significant predictor
      of absolute and percent prostate volume reduction. Total androgen suppression was
      associated with greater percent prostate volume reduction than luteinizing
      hormone releasing hormone agonist (LHRHa) alone (p = 0.001). CONCLUSIONS:
      Prostate volume decreased by approximately one third after 4.9 months of NHT,
      with total androgen suppression found to be more efficacious in maximizing
      cytoreduction than LHRHa alone. Initial prostate volume is the greatest predictor
      for prostate volume reduction.

PMID- 27895678
TI  - Prostate brachytherapy in Ghana: our initial experience.
AB  - PURPOSE: This study presents the experience of a brachytherapy team in Ghana with
      a focus on technology transfer and outcome. The team was initially proctored by
      experienced physicians from Europe and South Africa. MATERIAL AND METHODS: A
      total of 90 consecutive patients underwent either brachytherapy alone or
      brachytherapy in combination with external beam radiotherapy for prostate
      carcinoma between July 2008 and February 2014 at Korle Bu Teaching Hospital,
      Accra, Ghana. Patients were classified as low-risk, intermediate, and high-risk
      according to the National Comprehensive Cancer Network (NCCN) criteria. All low
      risk and some intermediate risk group patients were treated with seed
      implantation alone. Some intermediate and all high-risk group patients received
      brachytherapy combined with external beam radiotherapy. RESULTS: The median
      patient age was 64.0 years (range 46-78 years). The median follow-up was 58
      months (range 18-74 months). Twelve patients experienced biochemical failure
      including one patient who had evidence of metastatic disease and died of prostate
      cancer. Freedom from biochemical failure rates for low, intermediate, and high
      risk cases were 95.4%, 90.9%, and 70.8%, respectively. Clinical parameters
      predictive of biochemical outcome included: clinical stage, Gleason score, and
      risk group. Pre-treatment prostate specific antigen (PSA) was not a statistically
      significant predictor of biochemical failure. Sixty-nine patients (76.6%)
      experienced grade 1 urinary symptoms in the form of frequency, urgency, and poor
      stream. These symptoms were mostly self-limiting. Four patients needed
      catheterization for urinary retention (grade 2). One patient developed a recto
      urethral fistula (grade 3) following banding for hemorrhoids. CONCLUSIONS: Our
      results compare favorably with those reported by other institutions with more
      extensive experience. We believe therefore that, interstitial permanent
      brachytherapy can be safely and effectively performed in a resource challenged
      environment if adequate training and proctoring is provided.

PMID- 27895679
TI  - The impact of body mass index on dosimetric quality in low-dose-rate prostate
      brachytherapy.
AB  - PURPOSE: Low-dose-rate (LDR) brachytherapy has been established as an effective
      and safe treatment option for men with low and intermediate risk prostate cancer.
      In this retrospective analysis, we sought to study the effect of body mass index
      (BMI) on post-implant dosimetric quality. MATERIAL AND METHODS: After
      institutional approval, records of patients with non-metastatic prostate cancer
      treated in Puerto Rico with LDR brachytherapy during 2008-2013 were reviewed. All
      patients were implanted with 125I seeds to a prescription dose of 145 Gy.
      Computed tomography (CT) based dosimetry was performed 1 month after implant.
      Patients with at least 1 year of prostate-specific antigen (PSA) follow-up were
      included. Factors predictive of adequate D90 coverage (>= 140 Gy) were compared
      via the Pearson chi2 or Wilcoxon rank-sum test as appropriate. RESULTS: One
      hundred and four patients were included in this study, with 53 (51%) patients
      having a D90 >= 140 Gy. The only factor associated with a dosimetric coverage
      detriment (D90 < 140 Gy) was BMI >= 25 kg/m2 (p = 0.03). Prostate volume (p =
      0.26), initial PSA (p = 0.236), age (p = 0.49), hormone use (p = 0.93), percent
      of cores positive (p = 0.95), risk group (p = 0.24), tumor stage (p = 0.66), and
      Gleason score (p = 0.61) did not predict D90. CONCLUSIONS: In this study we show
      that BMI is a significant pre-implant predictor of D90 (< 140 Gy vs. >= 140 Gy).
      Although other studies have reported that prostate volume also affects D90, our
      study did not find this correlation to be statistically significant, likely
      because all of our patients had a prostate volume < 50 cc. Our study suggests
      that in patients with higher BMI values, more rigorous peri-implant dosimetric
      parameters may need to be applied in order to achieve a target D90 > 140 Gy.

PMID- 27895681
TI  - Rectal separation using hydroxypropyl methylcellulose in intracavitary
      brachytherapy of cervical cancer: an innovative approach.
AB  - PURPOSE: This study was initiated to prove feasibility of hydrogel application in
      recto-vaginal space in intracavitary brachytherapy (ICBT) of cervical cancer in
      order to reduce rectal toxicity. MATERIAL AND METHODS: In a case of stage IIB
      cervical cancer, after external beam radiotherapy (EBRT), we planned ICBT 7 Gy *
      3 fractions. In 1st fraction (Plan 1), due to narrow separation between rectum
      and cervix (0.18 cm), only 5 Gy was delivered at point A (with high-risk clinical
      target volume [HR-CTV] D90 5.94 Gy, intermediate risk clinical target volume [IR
      CTV] D90 4.54 Gy, rectum D2cc 5.72 Gy, bladder D2cc 5.52 Gy, and sigmoid colon
      5.82 Gy). In 2nd fraction (Plan 2), interstitial brachytherapy (ISBT) was
      attempted. For the prescription of 5 Gy, we get dose levels almost similar to the
      1st insertion: HR-CTV D90 (6.7 Gy), IR-CTV D90 (3.06 Gy), bladder D2cc (5.7 Gy),
      rectum D2cc (4.8 Gy), sigmoid colon D2cc (1.3 Gy) (separation = 0.23 cm). During
      3rd fraction (Plan 3), prior doing interstitial insertion, we instilled 50 cc of
      hydroxypropyl methylcellulose (Viscomet(r)) up to the tip of recto-vaginal
      septum. A repeat computed tomography (CT) scan was done 4 hours after Plan 3
      treatment and it was re-planned (Plan 4) to find out migration of hydrogel if any
      and its dosimetric impact. RESULTS: 9 Gy was delivered to point A with a
      separation of 1.1 cm in Plan 3 (with HR-CTV D90 16.4 Gy, IR-CTV D90 11.3 Gy,
      rectum D2cc 3.6 Gy, bladder D2cc 6.9 Gy, and sigmoid colon 2.2 Gy). We achieved
      an optimum cumulative EQD2 dose (HR-CTV D90 98.4 Gy, IR-CTV D90 76.1 Gy, rectum
      D2cc 67.7 Gy, bladder D2cc 73.2 Gy, and sigmoid colon 59.3 Gy). Hydrogel volume
      was decreased in Plan 4 without a major dosimetric changes. CONCLUSIONS: Hydrogel
      instillation is a useful tool for recto-vaginal separation during cervical cancer
      brachytherapy. It increases therapeutic ratio without any adverse event.

PMID- 27895680
TI  - The role of interstitial brachytherapy in the management of primary radiation
      therapy for uterine cervical cancer.
AB  - PURPOSE: The aim of this study was to report the clinical results of uterine
      cervical cancer patients treated by primary radiation therapy including
      brachytherapy, and investigate the role of interstitial brachytherapy (ISBT).
      MATERIAL AND METHODS: All consecutive uterine cervical cancer patients who were
      treated by primary radiation therapy were reviewed, and those who were treated by
      ISBT were further investigated for clinical outcomes and related toxicities.
      RESULTS: From December 2008 to October 2014, 209 consecutive uterine cervical
      cancer patients were treated with primary radiation therapy. Among them, 142 and
      42 patients were treated by intracavitary and hybrid brachytherapy, respectively.
      Twenty-five patients (12%) were treated by high-dose-rate (HDR)-ISBT. Five
      patients with distant metastasis other than para-aortic lymph node were excluded,
      and 20 patients consisted of the analysis. Three-year overall survival (OS),
      progression-free survival (PFS), and local control (LC) rate were 44.4%, 38.9%,
      and 87.8%, respectively. Distant metastasis was the most frequent site of first
      relapse after HDR-ISBT. One and four patients experienced grade 3 and 2 rectal
      bleeding, one grade 2 cystitis, and two grade 2 vaginal ulcer. CONCLUSIONS:
      Feasibility and favorable local control of interstitial brachytherapy for locally
      advanced cervical cancer was demonstrated through a single institutional
      experience with a small number of patients.

PMID- 27895683
TI  - Salvage interstitial brachytherapy based on computed tomography for recurrent
      cervical cancer after radical hysterectomy and adjuvant radiation therapy: case
      presentations and introduction of the technique.
AB  - PURPOSE: Locally recurring cervical cancer after surgery and adjuvant
      radiotherapy remains a major therapeutic challenge. This paper presents a new
      therapeutic technique for such patients: interstitial brachytherapy (BT) guided
      by real-time three-dimensional (3D) computed tomography (CT). MATERIAL AND
      METHODS: Sixteen patients with recurrent cervical cancer after radical surgery
      and adjuvant external-beam radiotherapy (EBRT) were included in this study. These
      patients underwent high-dose-rate (HDR) interstitial BT with free-hand placement
      of metal needles guided by real-time 3D-CT. Six Gy in 6 fractions were prescribed
      for the high-risk clinical target volume (HR-CTV). D90 and D100 for HR-CTV of BT,
      and the cumulative D2cc for the bladder, rectum, and sigmoid, including previous
      EBRT and present BT were analyzed. Treatment-related complications and 3-month
      tumor-response rates were investigated. RESULTS: The mean D90 value for HR-CTV
      was 52.5 +/- 3.3 Gy. The cumulative D2cc for the bladder, rectum, and sigmoid
      were 85.6 +/- 5.8, 71.6 +/- 6.4, and 69.6 +/- 5.9 Gy, respectively. The mean
      number of needles was 6.1 +/- 1.5, with an average depth of 3.5 +/- 0.9 cm for
      each application. Interstitial BT was associated with minor complications and
      passable tumor-response rate. CONCLUSIONS: Interstitial BT guided by real-time 3D
      CT for recurrent cervical cancer results in good dose-volume histogram (DVH)
      parameters. The current technique may be clinically feasible. However, long-term
      clinical outcomes should be further investigated.

PMID- 27895684
TI  - Investigation of the gold nanoparticles effects on the prostate dose distribution
      in brachytherapy: gel dosimetry and Monte Carlo method.
AB  - PURPOSE: In this work, gold nanoparticles (GNPs) were embedded in the MAGIC-f
      polymer gel irradiated with the 192Ir brachytherapy sources. MATERIAL AND
      METHODS: At the first plexiglas phantom was made as the human pelvis. The GNPs
      were synthesized with 15 nm in diameter and 0.1 mM (0.0197 mg/ml) in
      concentration by using a chemical reduction method. Then, the MAGIC-f gel was
      synthesized. The fabricated gel was poured into the tubes located at the prostate
      (with and without the GNPs) locations of the phantom. The phantom was irradiated
      with 192Ir brachytherapy sources for prostate cancer. After 24 hours, the
      irradiated gels was read by using Siemens 1.5 Tesla MRI scanner. Following the
      brachytherapy practices, the absolute doses at the reference points and isodose
      curves were extracted and compared by experimental measurements and Monte Carlo
      (MC) simulations. RESULTS: The mean absorbed doses in the presence of the GNPs in
      prostate were 14% higher than the corresponding values without the GNPs in the
      brachytherapy. The gamma index analysis (between gel and MC) using 7%/7 mm was
      also applied to the data and a high pass rate achieved (91.7% and 86.4% for
      analysis with/without GNPs, respectively). CONCLUSIONS: The real three
      dimensional analysis shows the comparison of the dose-volume histograms measured
      for planning volumes and the expected one from the MC calculation. The results
      indicate that the polymer gel dosimetry method, which developed and used in this
      study, could be recommended as a reliable method for investigating the dose
      enhancement factor of GNPs in brachytherapy.

PMID- 27895682
TI  - Development and clinical implementation of a new template for MRI-based
      intracavitary/interstitial gynecologic brachytherapy for locally advanced
      cervical cancer: from CT-based MUPIT to the MRI compatible Template Benidorm. Ten
      years of experience.
AB  - PURPOSE: To study outcome and toxicity in 59 patients with locally advanced
      cervix carcinoma treated with computed tomography (CT)-based Martinez universal
      perineal interstitial template (MUPIT) and the new magnetic resonance imaging
      (MRI)-compatible template Benidorm (TB). MATERIAL AND METHODS: From December 2005
      to October 2015, we retrospectively analyzed 34 patients treated with MUPIT and
      25 treated with the TB. Six 4 Gy fractions were prescribed to the clinical target
      volume (CTV) combined with external beam radiotherapy (EBRT). The organs at risk
      (OARs) and the CTV were delineated by CT scan in the MUPIT implants and by MRI in
      the TB implants. Dosimetry was CT-based for MUPIT and exclusively MRI-based for
      TB. Dose values were biologically normalized to equivalent doses in 2 Gy
      fractions (EQD2). RESULTS: Median CTV volumes were 163.5 cm3 for CT-based MUPIT
      (range 81.8-329.4 cm3) and 91.9 cm3 for MRI-based TB (range 26.2-161 cm3). Median
      D90 CTV (EBRT + BT) was 75.8 Gy for CT-based MUPIT (range 69-82 Gy) and 78.6 Gy
      for MRI-based TB (range 62.5-84.2 Gy). Median D2cm3 for the rectum was 75.3 Gy
      for CT-based MUPIT (range 69.8-132.1 Gy) and 69.9 Gy for MRI-based TB (range 58.3
      83.7 Gy). Median D2cm3 for the bladder was 79.8 Gy for CT-based MUPIT (range 71.2
      121.1 Gy) and 77.1 Gy for MRI-based TB (range 60.5-90.8 Gy). Local control (LC)
      was 88%. Overall survival (OS), disease free survival (DFS), and LC were not
      statistically significant in either group. Patients treated with CT-based MUPIT
      had a significantly higher percentage of rectal bleeding G3 (p = 0.040) than
      those treated with MRI-based TB, 13% vs. 2%. CONCLUSIONS: Template Benidorm
      treatment using MRI-based dosimetry provides advantages of MRI volume definition,
      and allows definition of smaller volumes that result in statistically significant
      decreased rectal toxicity compared to that seen with CT-based MUPIT treatment.

PMID- 27895685
TI  - Pediatric peri-operative fractionated high-dose-rate brachytherapy for recurrent
      Wilms' tumor using a reconstructed Freiburg flap.
AB  - PURPOSE: To report peri-operative fractionated high-dose-rate (HDR) brachytherapy
      with a 3D customized Freiburg flap applicator to treat locally recurrent Wilms'
      tumor, followed by immediate hyperthermic intraperitoneal chemotherapy for a 16
      year-old with a second recurrence of nephroblastoma (Wilms' tumor). MATERIAL AND
      METHODS: The tumor was excised and surgical bed was treated with fractionated HDR
      brachytherapy using a Freiburg flap applicator. Hyperthermic intraperitoneal
      chemotherapy was performed immediately after the removal of brachytherapy
      applicator. RESULTS: The Freiburg flap was successfully reconstructed to enable
      delivery of conformable peri-operative HDR brachytherapy. The clinical target
      volume (CTV) D90 was 26 Gy in 5 fractions. CONCLUSIONS: Peri-operative
      fractionated HDR brachytherapy with a customized Freiburg flap applicator was
      delivered successfully across a large multi-disciplinary team.

PMID- 27895686
TI  - Successful treatment of a 67-year-old woman with urethral adenocarcinoma with the
      use of external beam radiotherapy and image guided adaptive interstitial
      brachytherapy.
AB  - Primary urethral cancer (PUC) is a very rare disease. This case report
      illustrates a successful treatment approach of a 67-year-old woman with a
      urethral adenocarcinoma selected for an organ preserving treatment with external
      beam radiotherapy (EBRT) and interstitial brachytherapy (BT) boost, using the GEC
      ESTRO target concept originally designed for locally advanced cervical cancer
      (LACC). Treatment included EBRT with 45 Gy in 25 fractions followed by image
      guided adaptive interstitial BT (IGABT) with a pulsed-dose-rate (PDR) BT boost
      with 30 Gy in 50 hourly pulses. The D90 for CTVHR was 79.1 Gy in EQD23. At 24
      months follow-up, the patient was recurrence free and without treatment related
      side effects.

PMID- 27895687
TI  - Commissioning and quality assurance procedures for the HDR Valencia skin
      applicators.
AB  - The Valencia applicators (Nucletron, an Elekta company, Elekta AB, Stockholm,
      Sweden) are cup-shaped tungsten applicators with a flattening filter used to
      collimate the radiation produced by a high-dose-rate (HDR) 192Ir source, and
      provide a homogeneous absorbed dose at a given depth. This beam quality provides
      a good option for the treatment of skin lesions at shallow depth (3-4 mm). The
      user must perform commissioning and periodic testing of these applicators to
      guarantee the proper and safe delivery of the intended absorbed dose, as
      recommended in the standards in radiation oncology. In this study, based on AAPM
      and GEC-ESTRO guidelines for brachytherapy units and our experience, a set of
      tests for the commissioning and periodic testing of the Valencia applicators is
      proposed. These include general considerations, verification of the manufacturer
      documentation and physical integrity, evaluation of the source-to-indexer
      distance and reproducibility, setting the library plan in the treatment planning
      system, evaluation of flatness and symmetry, absolute output and percentage depth
      dose verification, independent calculation of the treatment time, and visual
      inspection of the applicator before each treatment. For each test, the proposed
      methodology, equipment, frequency, expected results, and tolerance levels (when
      applicable) are provided.

PMID- 27895688
TI  - Electromagnetic tracking for treatment verification in interstitial
      brachytherapy.
AB  - Electromagnetic tracking (EMT) is used in several medical fields to determine the
      position and orientation of dedicated sensors, e.g., attached to surgical tools.
      Recently, EMT has been introduced to brachytherapy for implant reconstruction and
      error detection. The manuscript briefly summarizes the main issues of EMT and
      error detection in brachytherapy. The potential and complementarity of EMT as
      treatment verification technology will be discussed in relation to in vivo
      dosimetry and imaging.

PMID- 27895689
TI  - Waist-to-height ratio as a screening tool for obesity and cardiometabolic risk.
AB  - The waist-to-height ratio (WHtR), calculated by dividing the waist circumference
      (WC) by height, has recently gained attention as an anthropometric index for
      central adiposity. It is an easy-to-use and less age-dependent index to identify
      individuals with increased cardiometabolic risk. A WHtR cutoff of 0.5 can be used
      in different sex and ethnic groups and is generally accepted as a universal
      cutoff for central obesity in children (aged >=6 years) and adults. However, the
      WHtR has not been validated in preschool children, and the routine use of WHtR in
      children under age 6 is not recommended. Prospective studies and meta-analysis in
      adults revealed that the WHtR is equivalent to or slightly better than WC and
      superior to body mass index (BMI) in predicting higher cardiometabolic risk. In
      children and adolescents, studies have shown that the WHtR is similar to both BMI
      and WC in identifying those at an increased cardiometabolic risk. Additional use
      of WHtR with BMI or WC may be helpful because WHtR considers both height and
      central obesity. WHtR may be preferred because of its simplicity and because it
      does not require sex- and age-dependent cutoffs; additionally, the simple message
      'keep your WC to less than half your height' may be particularly useful. This
      review article summarizes recent publications on the usefulness of using WHtR
      especially when compared to BMI and WC as a screening tool for obesity and
      related cardiometabolic risks, and recommends the use of WHtR in clinical
      practice for obesity screening in children and adolescents.

PMID- 27895691
TI  - Prognostic factors of neurological outcomes in late-preterm and term infants with
      perinatal asphyxia.
AB  - PURPOSE: This study aimed to identify prognostic factors of neurological
      outcomes, including developmental delay, cerebral palsy and epilepsy in late
      preterm and term infants with perinatal asphyxia. METHODS: All late-preterm and
      term infants with perinatal asphyxia or hypoxic-ischemic insults who admitted the
      neonatal intensive care unit of Inje University Sanggye Paik Hospital between
      2006 and 2014 and were followed up for at least 2 years were included in this
      retrospective study. Abnormal neurological outcomes were defined as cerebral
      palsy, developmental delay and epilepsy. RESULTS: Of the 114 infants with
      perinatal asphyxia, 31 were lost to follow-up. Of the remaining 83 infants, 10
      died, 56 had normal outcomes, and 17 had abnormal outcomes: 14 epilepsy (82.4%),
      13 cerebral palsy (76.5%), 16 developmental delay (94.1%). Abnormal outcomes were
      significantly more frequent in infants with later onset seizure, clinical
      seizure, poor electroencephalography (EEG) background activity, lower Apgar score
      at 1 and 5 minutes and abnormal brain imaging (P<0.05). Infants with and without
      epilepsy showed significant differences in EEG background activity, clinical and
      electrographic seizures on EEG, Apgar score at 5 minutes and brain imaging
      findings. CONCLUSION: We should apply with long-term video EEG or amplitude
      integrated EEG in order to detect and management subtle clinical or
      electrographic seizures in neonates with perinatal asphyxia. Also, long-term,
      prospective studies with large number of patients are needed to evaluate more
      exact prognostic factors in neonates with perinatal asphyxia.

PMID- 27895690
TI  - Rhinovirus and childhood asthma: an update.
AB  - Asthma is recognized as a complex disease resulting from interactions between
      multiple genetic and environmental factors. Accumulating evidence suggests that
      respiratory viral infections in early life constitute a major environmental risk
      factor for the development of childhood asthma. Respiratory viral infections have
      also been recognized as the most common cause of asthma exacerbation. The advent
      of molecular diagnostics to detect respiratory viruses has provided new insights
      into the role of human rhinovirus (HRV) infections in the pathogenesis of asthma.
      However, it is still unclear whether HRV infections cause asthma or if wheezing
      with HRV infection is simply a predictor of childhood asthma. Recent clinical and
      experimental studies have identified plausible pathways by which HRV infection
      could cause asthma, particularly in a susceptible host, and exacerbate disease.
      Airway epithelial cells, the primary site of infection and replication of HRV,
      play a key role in these processes. Details regarding the role of genetic
      factors, including ORMDL3, are beginning to emerge. This review discusses recent
      clinical and experimental evidence for the role of HRV infection in the
      development and exacerbation of childhood asthma and the potential underlying
      mechanisms that have been proposed.

PMID- 27895692
TI  - Impact of postoperative duration of Aspirin use on longevity of bioprosthetic
      pulmonary valve in patients who underwent congenital heart disease repair.
AB  - PURPOSE: Generally, aspirin is used as a protective agent against thrombogenic
      phenomenon after pulmonary valve replacement (PVR) using a bioprosthetic valve.
      However, the appropriate duration of aspirin use is unclear. We analyzed the
      impact of postoperative duration of aspirin use on the longevity of bioprosthetic
      pulmonary valves in patients who underwent repair for congenital heart diseases.
      METHODS: We retrospectively reviewed the clinical data of 137 patients who
      underwent PVR using a bioprosthetic valve between January 2000 and December 2003.
      Among these patients, 89 were included in our study and divided into groups I
      (<=12 months) and II (>12 months) according to duration of aspirin use. We
      analyzed echocardiographic data from 9 to 11 years after PVR. Pulmonary vale
      stenosis and regurgitation were classified as mild, moderate, or severe. RESULTS:
      The 89 patients consisted of 53 males and 36 females. Their mean age was 14.3+/
      8.9 years (range, 2.6-48 years) and body weight was 37.6+/-14.7 kg (range, 14-72
      kg). The postoperative duration of aspirin use was 7.3+/-2.9 months in group I
      and 32.8+/-28.4 months in group II. However, no significant difference in sex
      ratio, age, body weight, type of bioprosthetic valve, and number of early redo
      PVRs. In the comparison of echocardiographic data about 10 years later, no
      significant difference in pulmonary valve function was found. The overall freedom
      rate from redo-PVR at 10 years showed no significant difference (P=0.498).
      CONCLUSION: Our results indicated no benefit from long-term aspirin medication
      (>6 months) in patients who underwent PVR with a bioprosthetic valve.

PMID- 27895693
TI  - P wave dispersion on 12-lead electrocardiography in adolescents with
      neurocardiogenic syncope.
AB  - PURPOSE: Neurocardiogenic syncope (NCS) is the most frequent cause of fainting
      during adolescence. Inappropriate cardiovascular autonomic control may be
      responsible for this clinical event. The head-up tilt test has been considered a
      diagnostic standard, but it is cumbersome and has a high false-positive rate. We
      performed a study to evaluate whether P-wave dispersion (PWD) could be a useful
      electrocardiographic parameter of cardiac autonomic dysfunction in children with
      NCS. METHODS: Fifty-four patients with NCS (28 boys and 26 girls; mean age,
      12.3+/-1.4 years) and 55 age- and sex-matched healthy controls were enrolled. PWD
      was obtained as the difference between maximum and minimum durations of the P
      wave on standard 12-lead electrocardiography in all patients and controls.
      RESULTS: The value of PWD was significantly higher in the syncope group than in
      the control group (69.7+/-19.6 msec vs. 45.5+/-17.1 msec, respectively; P<0.001).
      The minimum duration of P wave was shorter in the syncope group than in the
      control group (43.8+/-16.8 msec vs. 53.5+/-10.7 msec, respectively; P<0.001).
      Left atrial volume was not different between the groups on transthoracic
      echocardiography. CONCLUSION: PWD on echocardiography could be used as a clinical
      parameter in patients with NCS.

PMID- 27895694
TI  - Edentulous child with Allgrove syndrome: a rare case report.
AB  - Triple-A syndrome, also known as Allgrove syndrome, is a rare autosomal recessive
      disorder. The 3 features of this syndrome are achalasia, adrenal insufficiency,
      and alacrima. Achalasia could be the first manifestation of the triple-A
      syndrome; however, its etiology is unclear. Alacrima is generally asymptomatic
      but can be detected by obtaining patient history. Although adrenal insufficiency
      could have manifestations such as asthenia, it might be wrongly diagnosed as
      muscle fatigue. Vitamin D and calcium supplements are usually prescribed for the
      prevention of osteoporosis. Neurologic manifestations could be present in adults.
      In some individuals with this disorder, genetic examination indicates mutations
      in both alleles of the AAAS gene, which encodes a special 546-amino-acid protein
      designated ALADIN, and in chromosome 12q13. The genetic cause of the triple A
      syndrome in some patients who do not have an identified mutation is unknown.
      While very few such cases have been reported till date, one such case was
      presented to us as an edentulous child.

PMID- 27895695
TI  - The Effects of Guizhi Fuling Capsule Drug Serum on Uterine Leiomyoma Cells and
      Its Mechanism.
AB  - Aims. To observe the effects of Guizhi Fuling Capsule (GZFLC) drug serum on
      uterine leiomyoma cells and explore its mechanism. Main Methods. Sixty Sprague
      Dawley rats were randomly divided into two groups (normal saline lavage group and
      GZFLC lavage group), then, respectively, blank serum and GZFLC drug serum were
      collected, and finally human uterine leiomyoma cells were treated. Human
      leiomyoma tissues were collected from 20 patients who underwent uterine
      leiomyomas operations, and leiomyoma cells were primary cultured. The leiomyoma
      cells were treated by GZFLC drug serum in different concentrations (10%, 20%, and
      30%) and variable treatment time (12 h, 24 h, 36 h, 48 h, and 72 h). Cell
      proliferation was observed using CCK8 assay. Flow cytometry and Annexin V/PI were
      used to assay the effects of GZFLC drug serum on cell apoptosis. Western blot
      analysis was used to assay the effects of GZFLC drug serum on TSC2, FOXO, and 14
      3-3gamma expression in uterine leiomyoma cells. Key Findings. In the
      concentrations of 10%~30%, GZFLC drug serum could inhibit proliferation of
      leiomyoma cells in dose-dependent manner; at the time of 36 h, cell inhibition
      rate was at the peak; GZFLC drug serum could induce apoptosis of leiomyoma also
      in a dose-dependent manner, and apoptosis rate quickly achieved maximum at 12 h
      time points, and then second apoptosis peak appeared at 36 h. Compared to
      nontreatment group, TSC2, FOXO, and 14-3-3gamma expressions in drug serum group
      were significantly changed after 12 h treatment. Significance. GZFLC drug serum
      can efficiently inhibit the proliferation and induce apoptosis of leiomyoma
      cells, which is related to the 14-3-3gamma pathway.

PMID- 27895696
TI  - Efficacy of Danlou Tablet in Patients with Non-ST Elevation Acute Coronary
      Syndrome Undergoing Percutaneous Coronary Intervention: Results from a
      Multicentre, Placebo-Controlled, Randomized Trial.
AB  - This study seeks to investigate potential cardioprotection of Danlou Tablets in
      patients undergoing PCI with non-ST elevation acute coronary syndrome (NSTE-ACS).
      219 patients with NSTE-ACS were randomised to Danlou Tablet pretreatment (n =
      109) or placebo (n = 110). No patients received statins prior to PCI and all
      patients were given atorvastatin (10 mg/day) after procedure. The main endpoint
      was the composite incidence of major adverse cardiac events (MACEs) within 30
      days after PCI. The proportion of patients with elevated levels of cTn I>5 * 99%
      of upper reference limit was significantly lower in the Danlou Tablet group at 8
      h (22.0% versus 34.5%, p = 0.04) and 24 h (23.9% versus 38.2%, p = 0.02) after
      PCI. The 30-day MACEs occurred in 22.0% of the Danlou Tablet group and 33.6% in
      the placebo group (p = 0.06). The incidence of MACE at 90-day follow-up was
      significantly decreased in the Danlou Tablet group compared to the placebo group
      (23.9% versus 37.3%, p = 0.03). The difference between the groups at 90 days was
      the incidence of nonfatal myocardial infarction (22% versus 34.5%, p = 0.04).
      These findings might support that treatment with Danlou Tablet could reduce the
      incidence of periprocedural myocardial infarction in patients with ACS undergoing
      PCI.

PMID- 27895699
TI  - Resilience and burnout status among nurses working in oncology.
AB  - BACKGROUND: This study aimed to identify the resilience and burnout status of
      nurses working in the field of oncology. METHODS: This descriptive study was
      conducted with 140 oncology nurses. The data were collected using a socio
      demographic attributes form, Resilience Scale for Adults, and the Maslach's
      Burnout Inventory. Percentage ratios, mean and median values, Kruskal-Wallis
      test, Mann-Whitney U test, correlation analysis, and multiple stepwise linear
      regression analysis were used to evaluate the data. RESULTS: The Maslach's
      Burnout Inventory total median score was 49.00. The emotional exhaustion median
      score was 24.00, the depersonalization median score was 9.00, and the personal
      accomplishment median score was 16.00. The Resilience Scale for Adults total
      median score was 134.00. The median resilience subscale scores, such as
      structural style, perception of future, family cohesion, self-perception, social
      competence, and social resources, were 16.00, 16.00, 24.00, 25, 23, and 31,
      respectively. A relationship existed between emotional exhaustion and perception
      of future; depersonalization and structured style and self-perception; and
      personal accomplishment and structured style, perception of future, and self
      perception. Multiple stepwise linear regression analysis revealed a significant
      relationship between the number of years in the field and emotional exhaustion
      and depersonalization scores. Moreover, a significant relationship between
      structured style variables and personal accomplishment scores was observed.
      CONCLUSIONS: This study demonstrated the relationship between burnout and
      resilience situations among the oncology nurses. The results can be used to plan
      individual and organizational interventions to increase resilience and reduce the
      experience of burnout by developing measures such as improving communication
      skills, providing education on stress management and coping strategies, using
      social resources, and organizing programs that provide psychological support.

PMID- 27895698
TI  - Combinations of bio-active dietary constituents affect human white adipocyte
      function in-vitro.
AB  - BACKGROUND: Specific bio-active dietary compounds modulate numerous metabolic
      processes in adipose tissue (AT), including pre-adipocyte proliferation and
      differentiation. AT dysfunction, rather than an increased fat mass per se, is
      strongly associated with the development of insulin resistance and is
      characterized by impaired adipogenesis, hypertrophic adipocytes, inflammation,
      and impairments in substrate metabolism. A better understanding of mechanisms
      underlying AT dysfunction may provide new strategies for the treatment of obesity
      associated metabolic diseases. Here we evaluated the role of (all-E)-lycopene
      (Lyc), eicosapentaenoic acid (EPA) or trans-resveratrol (Res) and combinations
      thereof on human white adipocyte function. METHODS: In-vitro differentiating
      human pre-adipocytes were treated with EPA, Lyc and Res or their combinations for
      14 days. The effects on intracellular lipid droplet (LD) accumulation, secreted
      anti- and pro-inflammatory cyto-/adipokines (e.g. adiponectin, IL-6, IL-8/CXCL-8
      and MCP-1/CCL2) and on gene expression of markers of adipocyte differentiation
      and substrate metabolism (e.g. PPAR-gamma, C/EBP-alpha, GLUT-4, FAS, ATGL, HSL,
      and PLIN-1) were measured by fluorescent microscopy (CellomicsTM), multi
      parametric LiquiChip(r) technology and quantitative RT-PCR, respectively.
      RESULTS: Treatment of differentiating adipocytes for 14 days with the combination
      of Lyc/Res and EPA/Res resulted in significantly inhibited LD formation (~ -25
      and -20%, respectively) compared to the effects of the single compounds. These
      morphological changes were accompanied by increased mRNA levels of the adipogenic
      marker PPAR-gamma and the lipase ATGL and by decreased expression levels of
      lipogenic markers (LPL, FAS, GLUT-4) and the LD-covering protein PLIN-1. In
      addition, a blunted adipocyte secretion of pro-inflammatory cytokines (IL-6 and
      MCP-1) and adiponectin was observed following treatment with these compounds.
      CONCLUSION: The combination of the dietary bio-actives Lyc and EPA with Res might
      influence adipocyte function by affecting the balance between adipogenic,
      lipogenic and lipolytic gene expression, resulting in a reduced LD storage and a
      less inflammatory secretion profile. Taken together, our results indicate that
      combinations of dietary compounds may be beneficial for the prevention and
      treatment of metabolic disorders via effects on human white adipocyte function.

PMID- 27895697
TI  - Trends in clinical characteristics and outcomes of Pre-ART care at a large HIV
      clinic in Nairobi, Kenya: a retrospective cohort study.
AB  - BACKGROUND: The success of antiretroviral therapy in resource-scarce settings is
      an illustration that complex healthcare interventions can be successfully
      delivered even in fragile health systems. Documenting the success factors in the
      scale-up of HIV care and treatment in resource constrained settings will enable
      health systems to prepare for changing population health needs. This study
      describes changing demographic and clinical characteristics of adult pre-ART
      cohorts, and identifies predictors of pre-ART attrition at a large urban HIV
      clinic in Nairobi, Kenya. METHODS: We conducted a retrospective cohort analysis
      of data on HIV infected adults (>=15 years) enrolling in pre-ART care between
      January 2004 and September 2015. Attrition (loss to program) was defined as those
      who died or were lost to follow-up (having no contact with the facility for at
      least 6 months). We used Kaplan-Meier survival analysis to determine time to
      event for the different modes of transition, and Cox proportional hazards models
      to determine predictors of pre-ART attrition. RESULTS: Over the 12 years of
      observation, there were increases in the proportions of young people (age 15 to
      24 years); and patients presenting with early disease (by WHO clinical stage and
      higher median CD4 cell counts), p = 0.0001 for trend. Independent predictors of
      attrition included: aHR (95% CI): male gender 1.98 (1.69-2.33), p = 0.0001; age
      20-24 years 1.80 (1.37-2.37), p = 0.0001), or 25-34 years 1.22 (1.01-1.47), p =
      0.0364; marital status single 1.55 (1.29-1.86), p = 0.0001) or divorced 1.41(1.02
      1.95), p = 0.0370; urban residency 1.83 (1.40-2.38), p = 0.0001; CD4 count of 0
      100 cells/ul 1.63 (1.003-2.658), p = 0.0486 or CD4 count >500 cells/ul 2.14(1.46
      3.14), p = 0.0001. CONCLUSIONS: In order to optimize the impact of HIV
      prevention, care and treatment in resource scarce settings, there is an urgent
      need to implement prevention and treatment interventions targeting young people
      and patients entering care with severe immunosuppression (CD4 cell counts <100
      cells/ul). Additionally, care and treatment programmes should strengthen inter
      facility referrals and linkages to improve care coordination and prevent leakages
      in the HIV care continuum.

PMID- 27895701
TI  - A DNA-based real-time PCR assay for robust growth quantification of the bacterial
      pathogen Pseudomonas syringae on Arabidopsis thaliana.
AB  - BACKGROUND: The interaction of Pseudomonas syringae with Arabidopsis is one of
      the most commonly used systems to study various bacterial-host
      interrelationships. Currently, most studies are based on the growth
      quantification of the pathogen to characterize resistance or virulence targets.
      However, the standard available method for determining bacterial proliferation in
      planta is laborious and has several limitations. RESULTS: Here we present an
      alternative robust approach, which is based on the quantification of bacterial
      DNA by real-time PCR. We directly compared this assay with the routinely used
      plate counting method to access bacterial titers in a number of well described
      Arabidopsis mutants. CONCLUSIONS: These studies showed that the DNA-based
      technique is highly reliable and comparable. Moreover, the technique is easily
      applicable, robust, and ideal for routine experiments or for larger scale
      analyses.

PMID- 27895700
TI  - Intervention based on BASNEF model increases exclusive breastfeeding in preterm
      infants in Iran: a randomized controlled trial.
AB  - BACKGROUND: The objective of this study is to determine the effect of a
      consultation model, Beliefs, Attitudes, Subjective Norms and Enabling Factors
      (BASNEF), and the counselling steps using GATHER-Greet clients, Ask clients about
      themselves, Tell clients about their choices, Help clients choose, Explain what
      to do, and Return for follow-up-on the continuation rates of exclusive
      breastfeeding in mothers of premature infants. METHODS: This is a randomized
      controlled clinical trial carried out on 124 mothers with premature infants
      hospitalized in Fatemieh Hospital, city of Hamadan, in 2014. Participants were
      randomly assigned to either the intervention or control groups. The initial
      demographic questionnaire carried out in both groups included three questions
      about the continuation of exclusive breastfeeding, BASNEF, a checklist related to
      the lactation performance documented by mothers and the weight gain of their
      infants. Five breastfeeding consultation sessions based on the BASNEF model and
      counselling steps using GATHER, were held for the mothers in the intervention
      group for five consecutive days. Then follow-up weight gain and the questionnaire
      completion were performed in both groups at 1, 2, 3 and 4 months after the
      intervention. RESULTS: Baseline characteristics were similar in the two groups.
      There were no significant differences between both groups in the rate of
      exclusive breastfeeding, lactation performance and infant weight at baseline. The
      intervention group had significantly higher rates of exclusive breastfeeding,
      72.6% versus the control group of 16.1%, at the end of the 4 month follow-up.
      Also the intervention group had significantly higher mean scores of lactation
      performance (8.62 +/- 2.08 vs 6.40 +/- 1.84 in the control group) and infant
      weight (5694.80 +/- 779.43 vs 4760.17 +/- 859.12 in the control group) at the end
      of the 4 month follow-up. CONCLUSION: Breastfeeding consultation of mothers based
      on the BASNEF model and using GATHER counselling steps increased the rate of
      exclusive breastfeeding, lactation performance and weight gain of premature
      infants. Therefore, breastfeeding counselling sessions are recommended for all
      mothers of premature infants. TRIAL REGISTRATION: Iranian Registry of Clinical
      Trials number IRCT2014111013405N6 and date registered, January 5, 2015.

PMID- 27895703
TI  - Changing Patterns of lung, liver, and head and neck non-AIDS-defining cancers
      relative to HIV status in Tanzania between 2002-2014.
AB  - BACKGROUND: Tanzania, like other low-income countries, has an increasing cancer
      burden that remains underestimated. Infection-associated malignancies,
      particularly HIV-infection, represent a great proportion of cancer burden in
      Tanzania and throughout Africa. Availability of HIV treatment and improved
      survival of HIV patients are suggested factors related to increasing prevalence
      of non-AIDS-defining cancers (NADCs). This study examined patterns of NADCs and
      proportions of HIV-positivity at the Ocean Road Cancer Institute (ORCI). METHODS:
      We reviewed logbooks of all ORCI patients diagnosed and/or treated for lung,
      liver, and head and neck cancers during 2002-2014. The number of total cancers
      diagnosed at ORCI during this period was used to calculate proportions of NADCs.
      We abstracted medical records to obtain demographic and clinical profiles and HIV
      status information for 1127 patients diagnosed or treated during 2010-2014.
      Trends in numbers and proportions of NADCs were analyzed using Joinpoint
      regression. Characteristics of NADC patients were analyzed using multinomial
      logistic regression. RESULTS: NADCs diagnosed at ORCI increased by 33.8% from
      2002 to 2014 while the proportion of NADCs relative to all cancers significantly
      decreased from 6.8% in 2002 to 5.6% in 2014 (APC = -2.74%). Numbers and
      proportions of lung and liver cancers increased compared to all cancer diagnoses
      from 2002 to 2014. The number of head and neck cancers increased while decreasing
      proportionally compared to all cancer diagnoses from 2002 to 2014. Among patients
      with pathologically confirmed NADCs between 2010 and 2014, HIV prevalence showed
      a non-statistically significant decrease from 8.1 to 7.1% (APC = -3.77%).
      CONCLUSIONS: Absolute numbers of lung, liver, and head and neck cancers increased
      at ORCI by 1/3 since 2002. Improving survivorship of HIV patients and varying
      immunodeficiency status may have contributed to the increasing number of NADCs.
      Total cancer diagnoses nearly doubled during this period, leading to a smaller
      relative proportion of NADCs diagnosed in 2014 compared to 2002. Late- stage
      diagnosis and short survival of NADCs included this study may explain possible
      underestimation and smaller increase in proportion of these particular NADCs
      compared to other NADCs studied in Tanzania. The slight decrease in proportion of
      HIV-positive NADC patients during 2010-2014 may suggest increasing patient
      longevity and more effective HIV management in Tanzania.

PMID- 27895702
TI  - Ameliorating effect of Erxian decoction combined with Fructus Schisandrae
      chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat
      model.
AB  - BACKGROUND: Modified Erxian decoction (MEXD), i.e., Erxian decoction (EXD) with
      Fructus Schisandrae chinensis (Wu Wei Zi) added, has been used to alleviate
      menopausal symptoms. This study aimed to investigate the effects of MEXD on
      menopausal sweating and serum hormone levels in a rat model of menopause after
      oral administration of MEXD. METHODS: Quality control of MEXD was conducted by
      employing a reversed-phase high performance liquid chromatography column. The
      three treatment groups received oral administration of MEXD in 0.5% sodium
      carboxylmethyl cellulose (CMC-Na) at three different doses (5.5, 11, and 22 g/kg
      body weight) once-daily for 6 consecutive weeks, with 10 animals per group.
      Huangqijing oral liquor (5 mL/kg) prepared from the roots of Huang qi (Astragalus
      membranaceus) with an antiperspirant effect was used as a positive control. The
      negative control group received the same volume of vehicle (0.5% CMC-Na). Ten 3
      month-old Sprague-Dawley rats were used as a young group for comparison with the
      treatment groups (12-14 months old rats). Blood was collected from all animals
      after 3-6 weeks of treatment. At the end of the treatment, the uterine weight,
      ovarian weight, and body weight were recorded. Serum malondialdehyde contents and
      superoxide dismutase activities were determined by thiobarbituric acid
      colorimetric assays and chemoluminescence assays, respectively. Serum levels of
      estradiol, follicle-stimulating hormone, and luteinizing hormone were measured by
      radioimmunoassays. Rat foot pad assays were used to determine the antiperspirant
      activity of MEXD and histological examinations were conducted on plantar sweat
      glands. RESULTS: Treatment with MEXD (11 g/kg) significantly inhibited sweat
      excretion in the menopause model rats after treatment for 3 (P = 0.0026) and 6 (P
      < 0.0001) weeks. The decoction markedly decreased the number of secretory cells
      in plantar sweat glands. In addition, MEXD (11 g/kg) significantly increased the
      serum estradiol levels (P < 0.001) and superoxide dismutase activities (P =
      0.0405). Furthermore, MEXD (11 g/kg) markedly decreased the serum levels of
      follicle-stimulating hormone (P = 0.001), luteinizing hormone (P = 0.0213), and
      malondialdehyde (P = 0.01). CONCLUSION: Modified Erxian decoction significantly
      inhibited sweat excretion, regulated serum levels of pituitary gonadotropins and
      estradiol, and exhibited antioxidative effects in a rat model of menopause.

PMID- 27895705
TI  - Improved sugar yields from biomass sorghum feedstocks: comparing low-lignin
      mutants and pretreatment chemistries.
AB  - BACKGROUND: For biofuel production processes to be economically efficient, it is
      essential to maximize the production of monomeric carbohydrates from the
      structural carbohydrates of feedstocks. One strategy for maximizing carbohydrate
      production is to identify less recalcitrant feedstock cultivars by performing
      some type of experimental screening on a large and diverse set of candidate
      materials, or by identifying genetic modifications (random or directed mutations
      or transgenic plants) that provide decreased recalcitrance. Economic efficiency
      can also be increased using additional pretreatment processes such as
      deacetylation, which uses dilute NaOH to remove the acetyl groups of
      hemicellulose prior to dilute acid pretreatment. In this work, we used a
      laboratory-scale screening tool that mimics relevant thermochemical pretreatment
      conditions to compare the total sugar yield of three near-isogenic brown midrib
      (bmr) mutant lines and the wild-type (WT) sorghum cultivar. We then compared
      results obtained from the laboratory-scale screening pretreatment assay to a
      large-scale pretreatment system. RESULTS: After pretreatment and enzymatic
      hydrolysis, the bmr mutants had higher total sugar yields than the WT sorghum
      cultivar. Increased pretreatment temperatures increased reactivity for all
      sorghum samples reducing the differences observed at lower reaction temperatures.
      Deacetylation prior to dilute acid pretreatment increased the total sugar yield
      for all four sorghum samples, and reduced the differences in total sugar yields
      among them, but solubilized a sizable fraction of the non-structural
      carbohydrates. The general trends of increased total sugar yield in the bmr
      mutant compared to the WT seen at the laboratory scale were observed at the large
      scale system. However, in the larger reactor system, the measured total sugar
      yields were lower and the difference in total sugar yield between the WT and bmr
      sorghum was larger. CONCLUSIONS: Sorghum bmr mutants, which have a reduced lignin
      content showed higher total sugar yields than the WT cultivar after dilute acid
      pretreatment and enzymatic hydrolysis. Deacetylation prior to dilute acid
      pretreatment increased the total sugar yield for all four sorghum samples.
      However, since deacetylation also solubilizes a large fraction of the non
      structural carbohydrates, the ability to derive value from these solubilized
      sugars will depend greatly on the proposed conversion process.

PMID- 27895704
TI  - The extracellular microscape governs mesenchymal stem cell fate.
AB  - Each cell forever interacts with its extracellular matrix (ECM); a stem cell
      relies on this interaction to guide differentiation. The stiffness,
      nanotopography, protein composition, stress and strain inherent to any given ECM
      influences stem cell lineage commitment. This interaction is dynamic,
      multidimensional and reciprocally evolving through time, and from this concerted
      exchange the macroscopic tissues that comprise living organisms are formed.
      Mesenchymal stem cells can give rise to bone, cartilage, tendon and muscle; thus
      attempts to manipulate their differentiation must heed the physical properties of
      incredibly complex native microenvironments to realize regenerative goals.

PMID- 27895706
TI  - Whole-genome metabolic model of Trichoderma reesei built by comparative
      reconstruction.
AB  - BACKGROUND: Trichoderma reesei is one of the main sources of biomass-hydrolyzing
      enzymes for the biotechnology industry. There is a need for improving its enzyme
      production efficiency. The use of metabolic modeling for the simulation and
      prediction of this organism's metabolism is potentially a valuable tool for
      improving its capabilities. An accurate metabolic model is needed to perform
      metabolic modeling analysis. RESULTS: A whole-genome metabolic model of T. reesei
      has been reconstructed together with metabolic models of 55 related species using
      the metabolic model reconstruction algorithm CoReCo. The previously published
      CoReCo method has been improved to obtain better quality models. The main
      improvements are the creation of a unified database of reactions and compounds
      and the use of reaction directions as constraints in the gap-filling step of the
      algorithm. In addition, the biomass composition of T. reesei has been measured
      experimentally to build and include a specific biomass equation in the model.
      CONCLUSIONS: The improvements presented in this work on the CoReCo pipeline for
      metabolic model reconstruction resulted in higher-quality metabolic models
      compared with previous versions. A metabolic model of T. reesei has been created
      and is publicly available in the BIOMODELS database. The model contains a biomass
      equation, reaction boundaries and uptake/export reactions which make it ready for
      simulation. To validate the model, we dem1onstrate that the model is able to
      predict biomass production accurately and no stoichiometrically infeasible yields
      are detected. The new T. reesei model is ready to be used for simulations of
      protein production processes.

PMID- 27895707
TI  - Fungal fermentation on anaerobic digestate for lipid-based biofuel production.
AB  - BACKGROUND: Anaerobic digestate is the effluent from anaerobic digestion of
      organic wastes. It contains a significant amount of nutrients and lignocellulosic
      materials, even though anaerobic digestion consumed a large portion of organic
      matters in the wastes. Utilizing the nutrients and lignocellulosic materials in
      the digestate is critical to significantly improve efficiency of anaerobic
      digestion technology and generate value-added chemical and fuel products from the
      organic wastes. Therefore, this study focused on developing an integrated process
      that uses biogas energy to power fungal fermentation and converts remaining
      carbon sources, nutrients, and water in the digestate into biofuel precursor
      lipid. RESULTS: The process contains two unit operations of anaerobic digestion
      and digestate utilization. The digestate utilization includes alkali treatment of
      the mixture feed of solid and liquid digestates, enzymatic hydrolysis for mono
      sugar release, overliming detoxification, and fungal fermentation for lipid
      accumulation. The experimental results conclude that 5 h and 30  degrees C were
      the preferred conditions for the overliming detoxification regarding lipid
      accumulation of the following fungal cultivation. The repeated-batch fungal
      fermentation enhanced lipid accumulation, which led to a final lipid
      concentration of 3.16 g/L on the digestate with 10% dry matter. The mass and
      energy balance analysis further indicates that the digestate had enough water for
      the process uses and the biogas energy was able to balance the needs of
      individual unit operations. CONCLUSIONS: A fresh-water-free and energy-positive
      process of lipid production from anaerobic digestate was achieved by integrating
      anaerobic digestion and fungal fermentation. The integration addresses the issues
      that both biofuel industry and waste management encounter-high water and energy
      demand of biofuel precursor production and few digestate utilization approaches
      of organic waste treatment.

PMID- 27895708
TI  - Continuous production of biohythane from hydrothermal liquefied cornstalk biomass
      via two-stage high-rate anaerobic reactors.
AB  - BACKGROUND: Biohythane production via two-stage fermentation is a promising
      direction for sustainable energy recovery from lignocellulosic biomass. However,
      the utilization of lignocellulosic biomass suffers from specific natural
      recalcitrance. Hydrothermal liquefaction (HTL) is an emerging technology for the
      liquefaction of biomass, but there are still several challenges for the coupling
      of HTL and two-stage fermentation. One particular challenge is the limited
      efficiency of fermentation reactors at a high solid content of the treated
      feedstock. Another is the conversion of potential inhibitors during fermentation.
      Here, we report a novel strategy for the continuous production of biohythane from
      cornstalk through the integration of HTL and two-stage fermentation. Cornstalk
      was converted to solid and liquid via HTL, and the resulting liquid could be
      subsequently fed into the two-stage fermentation systems. The systems consisted
      of two typical high-rate reactors: an upflow anaerobic sludge blanket (UASB) and
      a packed bed reactor (PBR). The liquid could be efficiently converted into
      biohythane via the UASB and PBR with a high density of microbes at a high organic
      loading rate. RESULTS: Biohydrogen production decreased from 2.34 L/L/day in UASB
      (1.01 L/L/day in PBR) to 0 L/L/day as the organic loading rate (OLR) of the HTL
      liquid products increased to 16 g/L/day. The methane production rate achieved a
      value of 2.53 (UASB) and 2.54 L/L/day (PBR), respectively. The energy and carbon
      recovery of the integrated HTL and biohythane fermentation system reached up to
      79.0 and 67.7%, respectively. The fermentation inhibitors, i.e., 5-hydroxymethyl
      furfural (41.4-41.9% of the initial quantity detected) and furfural (74.7-85.0%
      of the initial quantity detected), were degraded during hydrogen fermentation.
      Compared with single-stage fermentation, the methane process during two-stage
      fermentation had a more efficient methane production rate, acetogenesis, and COD
      removal. The microbial distribution via Illumina MiSeq sequencing clarified that
      the biohydrogen process in the two-stage systems functioned not only for
      biohydrogen production, but also for the degradation of potential inhibitors. The
      higher distribution of the detoxification family Clostridiaceae, Bacillaceae, and
      Pseudomonadaceae was found in the biohydrogen process. In addition, a higher
      distribution of acetate-oxidizing bacteria (Spirochaetaceae) was observed in the
      biomethane process of the two-stage systems, revealing improved acetogenesis
      accompanied with an efficient conversion of acetate. CONCLUSIONS: Biohythane
      production could be a promising process for the recovery of energy and
      degradation of organic compounds from hydrothermal liquefied biomass. The two
      stage process not only contributed to the improved quality of the gas fuels but
      also strengthened the biotransformation process, which resulted from the function
      of detoxification during biohydrogen production and enhanced acetogenesis during
      biomethane production.

PMID- 27895709
TI  - The dilemma for lipid productivity in green microalgae: importance of substrate
      provision in improving oil yield without sacrificing growth.
AB  - Rising oil prices and concerns over climate change have resulted in more emphasis
      on research into renewable biofuels from microalgae. Unlike plants, green
      microalgae have higher biomass productivity, will not compete with food and
      agriculture, and do not require fertile land for cultivation. However, microalgae
      biofuels currently suffer from high capital and operating costs due to low yields
      and costly extraction methods. Microalgae grown under optimal conditions produce
      large amounts of biomass but with low neutral lipid content, while microalgae
      grown in nutrient starvation accumulate high levels of neutral lipids but are
      slow growing. Producing lipids while maintaining high growth rates is vital for
      biofuel production because high biomass productivity increases yield per harvest
      volume while high lipid content decreases the cost of extraction per unit
      product. Therefore, there is a need for metabolic engineering of microalgae to
      constitutively produce high amounts of lipids without sacrificing growth.
      Substrate availability is a rate-limiting step in balancing growth and fatty acid
      (FA) production because both biomass and FA synthesis pathways compete for the
      same substrates, namely acetyl-CoA and NADPH. In this review, we discuss the
      efforts made for improving biofuel production in plants and microorganisms, the
      challenges faced in achieving lipid productivity, and the important role of
      precursor supply for FA synthesis. The main focus is placed on the enzymes which
      catalyzed the reactions supplying acetyl-CoA and NADPH.

PMID- 27895710
TI  - In situ label-free imaging of hemicellulose in plant cell walls using stimulated
      Raman scattering microscopy.
AB  - BACKGROUND: Plant hemicellulose (largely xylan) is an excellent feedstock for
      renewable energy production and second only to cellulose in abundance. Beyond a
      source of fermentable sugars, xylan constitutes a critical polymer in the plant
      cell wall, where its precise role in wall assembly, maturation, and
      deconstruction remains primarily hypothetical. Effective detection of xylan,
      particularly by in situ imaging of xylan in the presence of other biopolymers,
      would provide critical information for tackling the challenges of understanding
      the assembly and enhancing the liberation of xylan from plant materials. RESULTS:
      Raman-based imaging techniques, especially the highly sensitive stimulated Raman
      scattering (SRS) microscopy, have proven to be valuable tools for label-free
      imaging. However, due to the complex nature of plant materials, especially those
      same chemical groups shared between xylan and cellulose, the utility of specific
      Raman vibrational modes that are unique to xylan have been debated. Here, we
      report a novel approach based on combining spectroscopic analysis and
      chemical/enzymatic xylan removal from corn stover cell walls, to make progress in
      meeting this analytical challenge. We have identified several Raman peaks
      associated with xylan content in cell walls for label-free in situ imaging xylan
      in plant cell wall. CONCLUSION: We demonstrated that xylan can be resolved from
      cellulose and lignin in situ using enzymatic digestion and label-free SRS
      microscopy in both 2D and 3D. We believe that this novel approach can be used to
      map xylan in plant cell walls and that this ability will enhance our
      understanding of the role played by xylan in cell wall biosynthesis and
      deconstruction.

PMID- 27895712
TI  - Philadelphia chromosome duplication as a ring-shaped chromosome.
AB  - The gain of a second copy of the Philadelphia chromosome is one of the main
      secondary chromosomal changes related to the clonal evolution of cells with
      t(9;22) in chronic myelogenous leukemia. This gain causes the acquisition of
      another copy of the BCR/ABL1 fusion gene. Isochromosomes of the der(22)
      chromosome or double minute chromosomes are well known to lead an increased copy
      number of BCR/ABL1 gene. There is no antecedent of Philadelphia chromosome
      duplication as a ring chromosome. A recent published report contains evidence
      that strongly suggests that the Philadelphia chromosome was duplicated as a ring
      chromosome, observation that was overlooked by the authors. The instability
      inherent to the ring chromosome increases the risk of emergence of clones
      containing more and more BCR/ABL1 gene copies, which would produce increased
      fitness for clonal selection, resulting in worsening of the patient's prognosis.

PMID- 27895711
TI  - Erratum to: Subtelomeric multiplex ligation-dependent probe amplification as a
      supplement for rapid prenatal detection of fetal chromosomal aberrations.
AB  - [This corrects the article DOI: 10.1186/s13039-014-0096-1.].

PMID- 27895713
TI  - Coexistence of iAMP21 and ETV6-RUNX1 fusion in an adolescent with B cell acute
      lymphoblastic leukemia: literature review of six additional cases.
AB  - BACKGROUND: Intrachromosomal amplification of chromosome 21 (iAMP21) results from
      breakage-fusion-bridge cycles and chromothripsis is a distinct marker of a
      subgroup of B cell acute lymphoblastic leukemia (B-ALL) cases associated with a
      poor prognosis. iAMP21 accounts for 2% of pediatric B-ALL and occurs
      predominantly in older children or adolescents. ETV6-RUNX1 fusion, resulting from
      t(12;21)(p13;q22), is associated with an excellent outcome in younger children
      with B-ALL. Coexistence of iAMP21 with ETV6-RUNX1 fusion is extremely rare with
      limited clinical information available. RESULTS: We report the case of an 18-year
      old Caucasian man diagnosed with ETV6-RUNX1 fusion positive B-ALL. He was treated
      with intensive chemotherapy and achieved remission for 6 months before relapse,
      15 months after the initial diagnosis. G-band karyotyping and Fluorescence in
      situ hybridization (FISH) analyses performed on bone marrow revealed complex
      abnormalities: 41,X,-Y,der(3)t(3;20)(p11.2;q11.2),
      4,t(5;22)(q32;q11.2),del(9)(p13),dic(9;17)(p13;p11.2),t(12;21)(p13;q22),der(14)t(
      4;17)(p11.2;q11.2),der(17;22)(q11.2;q11.2),-20,add(21)(q22),-22[4]/46,XY[15] with
      an iAMP21 and an ETV6-RUNX1. Additional molecular studies confirmed ETV6-RUNX1
      fusion and with a TP53 mutation. High-resolution single nucleotide polymorphism
      microarray (SNP array) revealed the iAMP21 to be chromothripsis of 21q and
      subsequent metaphase FISH further delineated complex genomic aberrations.
      Although the patient received intensive chemotherapy with allogenic stem cell
      transplant, he died 26 months after initial diagnosis. We searched the literature
      and identified six cases showing coexisting iAMP21 and ETV6-RUNX1. The median age
      for these six patients was 10 years (range, 2-18) and males predominated. The
      median overall survival (OS) was 28 months. CONCLUSIONS: Patients with B-ALL
      associated with both iAMP21 and ETV6-RUNX1 tend to be older children or
      adolescents and have a poor prognosis.

PMID- 27895714
TI  - Early detection and personalized treatment in oral cancer: the impact of omics
      approaches.
AB  - BACKGROUND: Oral cancer is one of the most common malignant lesions of the head
      and neck. This cancer is an aggressive and lethal disease with no significant
      improvements in the overall survival in the last decades. Moreover, the incidence
      of oral HPV-positive tumors is rising, especially in young people. This oral
      neoplasm develops through numerous molecular imbalances that affect key genes and
      signaling pathways; however, the molecular mechanisms involved in the
      pathogenesis and progression of oral tumors are still to be fully determined. In
      order to improve the quality of life and long-term survival rate of these
      patients, it is vital to establish accurate biomarkers that help in the early
      diagnosis, prognosis and development of target treatments. Such biomarkers may
      possibly allow for selection of patients that will benefit from each therapy
      modality, helping in the optimization of intensity and sequence of the treatments
      in order to decrease side effects and improve survival. CONCLUSION: In this
      review we discuss the current knowledge of oral cancer and the potential role of
      omics approaches to identify molecular biomarkers in the improvement of early
      diagnosis, treatment and prognosis. The pursuit to improve the quality of life
      and decrease mortality rates of the oral patients needs to be centralized on the
      identification of critical genes in oral carcinogenesis. Understanding the
      molecular biology of oral cancer is vital for search new therapies, being the
      molecular-targeted therapies the most promising treatment for these patients.

PMID- 27895715
TI  - Protein kinase Msk1 physically and functionally interacts with the KMT2A/MLL1
      methyltransferase complex and contributes to the regulation of multiple target
      genes.
AB  - BACKGROUND: The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic
      regulator of selected developmental genes, in part through the SET domain
      catalysed methylation of H3K4. It is essential for normal embryonic development
      and haematopoiesis and frequently mutated in cancer. The catalytic properties and
      targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the
      post-translational protein modifications which some of these proteins put in
      place, though detailed mechanisms remain unclear. RESULTS: KMT2A/MLL1 (both
      native and FLAG-tagged) and Msk1 (RPS6KA5) co-immunoprecipitated in various cell
      types. KMT2A/MLL1 and Msk1 knockdown demonstrated that the great majority of
      genes whose activity changed on KTM2A/MLL1 knockdown, responded comparably to
      Msk1 knockdown, as did levels of H3K4 methylation and H3S10 phosphorylation at
      KTM2A target genes HoxA4, HoxA5. Knockdown experiments also showed that
      KMT2A/MLL1 is required for the genomic targeting of Msk1, but not vice versa.
      CONCLUSION: The KMT2A/MLL1 complex is associated with, and functionally dependent
      upon, the kinase Msk1, part of the MAP kinase signalling pathway. We propose that
      Msk1-catalysed phosphorylation at H3 serines 10 and 28, supports H3K4 methylation
      by the KMT2A/MLL1 complex both by making H3 a more attractive substrate for its
      SET domain, and improving target gene accessibility by prevention of HP1- and
      Polycomb-mediated chromatin condensation.

PMID- 27895716
TI  - Widespread recovery of methylation at gametic imprints in hypomethylated mouse
      stem cells following rescue with DNMT3A2.
AB  - BACKGROUND: Imprinted loci are paradigms of epigenetic regulation and are
      associated with a number of genetic disorders in human. A key characteristic of
      imprints is the presence of a gametic differentially methylated region (gDMR).
      Previous studies have indicated that DNA methylation lost from gDMRs could not be
      restored by DNMT1, or the de novo enzymes DNMT3A or 3B in stem cells, indicating
      that imprinted regions must instead undergo passage through the germline for
      reprogramming. However, previous studies were non-quantitative, were unclear on
      the requirement for DNMT3A/B and showed some inconsistencies. In addition, new
      putative gDMR has recently been described, along with an improved delineation of
      the existing gDMR locations. We therefore aimed to re-examine the dependence of
      methylation at gDMRs on the activities of the methyltransferases in mouse
      embryonic stem cells (ESCs). RESULTS: We examined the most complete current set
      of imprinted gDMRs that could be assessed using quantitative pyrosequencing
      assays in two types of ESCs: those lacking DNMT1 (1KO) and cells lacking a
      combination of DNMT3A and DNMT3B (3abKO). We further verified results using
      clonal analysis and combined bisulfite and restriction analysis. Our results
      showed that loss of methylation was approximately equivalent in both cell types.
      1KO cells rescued with a cDNA-expressing DNMT1 could not restore methylation at
      the imprinted gDMRs, confirming some previous observations. However, nearly all
      gDMRs were remethylated in 3abKO cells rescued with a DNMT3A2 expression
      construct (3abKO + 3a2). Transcriptional activity at the H19/Igf2 locus also
      tracked with the methylation pattern, confirming functional reprogramming in the
      latter. CONCLUSIONS: These results suggested (1) a vital role for DNMT3A/B in
      methylation maintenance at imprints, (2) that loss of DNMT1 and DNMT3A/B had
      equivalent effects, (3) that rescue with DNMT3A2 can restore imprints in these
      cells. This may provide a useful system in which to explore factors influencing
      imprint reprogramming.

PMID- 27895718
TI  - Consensus Diversity Plots: a global diversity analysis of chemical libraries.
AB  - BACKGROUND: Measuring the structural diversity of compound databases is relevant
      in drug discovery and many other areas of chemistry. Since molecular diversity
      depends on molecular representation, comprehensive chemoinformatic analysis of
      the diversity of libraries uses multiple criteria. For instance, the diversity of
      the molecular libraries is typically evaluated employing molecular scaffolds,
      structural fingerprints, and physicochemical properties. However, the assessment
      with each criterion is analyzed independently and it is not straightforward to
      provide an evaluation of the "global diversity". RESULTS: Herein the Consensus
      Diversity Plot (CDP) is proposed as a novel method to represent in low dimensions
      the diversity of chemical libraries considering simultaneously multiple molecular
      representations. We illustrate the application of CDPs to classify eight compound
      data sets and two subsets with different sizes and compositions using molecular
      scaffolds, structural fingerprints, and physicochemical properties. CONCLUSIONS:
      CDPs are general data mining tools that represent in two-dimensions the global
      diversity of compound data sets using multiple metrics. These plots can be
      constructed using single or combined measures of diversity. An online version of
      the CDPs is freely available at: https://consensusdiversityplots-difacquim
      unam.shinyapps.io/RscriptsCDPlots/.Graphical AbstractConsensus Diversity Plot is
      a novel data mining tool that represents in two-dimensions the global diversity
      of compound data sets using multiple metrics.

PMID- 27895717
TI  - Interferon-gamma promotes gastric lymphoid follicle formation but not gastritis
      in Helicobacter-infected BALB/c mice.
AB  - BACKGROUND: Mouse infection studies have shown that interferon-gamma (IFN-gamma),
      a T helper 1 (Th1) cytokine, is required for the development of severe pathology
      induced by chronic Helicobacter infection. This finding is largely based on
      studies performed using mice that have polarised Th1 responses i.e. C57BL/6
      animals. The current work aims to investigate the role of IFN-gamma in
      Helicobacter-induced inflammation in BALB/c mice which have Th2-polarised immune
      responses. RESULTS: At 7 months post-infection with Helicobacter felis, IFN-gamma
      deficiency in BALB/c mice had no significant effect on H. felis colonisation
      levels in the gastric mucosa, nor on humoral responses, or gastritis severity.
      Ifng-/- animals with chronic H. felis infection did, however, develop
      significantly fewer lymphoid follicle lesions, as well as increased IL-4
      splenocyte responses, when compared with infected Ifng+/+ mice (P = 0.015 and P =
      0.0004, respectively). CONCLUSIONS: The work shows that in mice on a BALB/c
      background, IFN-gamma is not required for bacterial clearance, antibody
      responses, nor gastric inflammation. Conversely, IFN-gamma appears to play a role
      in the development of gastric lymphoid follicles, which are precursor lesions to
      mucosa-associated lymphoid tissue (MALT) lymphoma. This study highlights the
      importance of mouse host background on the susceptibility to Helicobacter-induced
      pathologies.

PMID- 27895719
TI  - DRABAL: novel method to mine large high-throughput screening assays using
      Bayesian active learning.
AB  - BACKGROUND: Mining high-throughput screening (HTS) assays is key for enhancing
      decisions in the area of drug repositioning and drug discovery. However, many
      challenges are encountered in the process of developing suitable and accurate
      methods for extracting useful information from these assays. Virtual screening
      and a wide variety of databases, methods and solutions proposed to-date, did not
      completely overcome these challenges. This study is based on a multi-label
      classification (MLC) technique for modeling correlations between several HTS
      assays, meaning that a single prediction represents a subset of assigned
      correlated labels instead of one label. Thus, the devised method provides an
      increased probability for more accurate predictions of compounds that were not
      tested in particular assays. RESULTS: Here we present DRABAL, a novel MLC
      solution that incorporates structure learning of a Bayesian network as a step to
      model dependency between the HTS assays. In this study, DRABAL was used to
      process more than 1.4 million interactions of over 400,000 compounds and analyze
      the existing relationships between five large HTS assays from the PubChem
      BioAssay Database. Compared to different MLC methods, DRABAL significantly
      improves the F1Score by about 22%, on average. We further illustrated usefulness
      and utility of DRABAL through screening FDA approved drugs and reported ones that
      have a high probability to interact with several targets, thus enabling drug
      multi-target repositioning. Specifically DRABAL suggests the Thiabendazole drug
      as a common activator of the NCP1 and Rab-9A proteins, both of which are designed
      to identify treatment modalities for the Niemann-Pick type C disease. CONCLUSION:
      We developed a novel MLC solution based on a Bayesian active learning framework
      to overcome the challenge of lacking fully labeled training data and exploit
      actual dependencies between the HTS assays. The solution is motivated by the need
      to model dependencies between existing experimental confirmatory HTS assays and
      improve prediction performance. We have pursued extensive experiments over
      several HTS assays and have shown the advantages of DRABAL. The datasets and
      programs can be downloaded from
      https://figshare.com/articles/DRABAL/3309562.Graphical abstract.

PMID- 27895720
TI  - Increased carotid intima-media thickness in Brazilian adolescents with type 1
      diabetes mellitus.
AB  - BACKGROUND: Increased carotid intima-media thickness (CIMT), a marker of
      subclinical atherosclerosis, is an independent predictor of future cardiovascular
      events, and has been reported in children with various chronic diseases,
      including type 1 diabetes mellitus (DM1). OBJECTIVES: Evaluate CIMT and its
      association with cardiovascular risk factors in Brazilian adolescents with DM1.
      METHODS: Cross-sectional study of 118 adolescents, 57 with DM1 and no chronic
      complications related to the disease, and 61 healthy individuals. Clinical,
      biochemical, and high-resolution B-mode ultrasonographic evaluations according to
      the Consensus Statement of the American Society of Echocardiography CIMT Task
      Force were performed. RESULTS: Adolescents with diabetes (66.6% female) were 14.5
      +/- 2.9 years old and had 9.0 +/- 4.0 years of disease duration. The healthy
      adolescents (62.3% female) were 14.3 +/- 2.6 years old. All the adolescents had
      blood pressure within their reference ranges. In 66% of DM1 adolescents the
      systolic blood pressure was >50th percentile. Increased CIMT was observed in
      adolescents with diabetes compared with those in the control group: 0.53 vs 0.51
      mm (p < 0.004) on the right side, and 0.55 vs 0.51 mm (p < 0.001) on the left
      side. CIMT presented independent and positive associations with diabetes
      duration, total cholesterol level, low-density lipoprotein cholesterol level, and
      systolic blood pressure percentile in DM1 adolescents. CONCLUSIONS: Increased
      CIMT was observed in young Brazilian adolescents with DM1, and was associated
      with cardiovascular risk factors. CIMT assessment may be useful for the early
      identification and monitoring of cardiovascular risk in this age group.

PMID- 27895721
TI  - Hypoadiponectinemia and the presence of metabolic syndrome in patients with
      chronic kidney disease: results from the KNOW-CKD study.
AB  - BACKGROUND: In patients with chronic kidney disease, metabolic syndrome has been
      demonstrated to be the culprit behind diverse complications. Adiponectin is known
      to have anti-atherogenic and cardio-protective effects. Meanwhile, the
      relationship between adiponectin and metabolic syndrome in patients with chronic
      kidney disease has not been clarified. The aim of this study was to elucidate the
      relationship between adiponectin level and metabolic syndrome in patients with
      chronic kidney disease. METHODS: The KoreaN Cohort Study for Outcome in Patients
      with Chronic Kidney Disease is a cohort study that enrolled subjects with chronic
      kidney disease throughout South Korea. From February 2011 to July 2014, data were
      collected from 1332 patients with chronic kidney disease. RESULTS: The mean age
      of the patients was 53.5 years and 803 patients (60.7%) were men. The median
      adiponectin level was 10.7 MUg/mL and 585 (44.3%) patients had metabolic
      syndrome. In multiple linear regression analysis, log adiponectin was positively
      associated with high-density lipoprotein cholesterol levels (beta = 0.006),
      whereas it was negatively associated with serum albumin (beta = -0.284),
      triglyceride (log beta = -0.288), high sensitivity C-reactive protein (log beta =
      -0.058) levels and estimated glomerular filtration rate (beta = -0.005). Multiple
      logistic regression analysis indicated that low adiponectin level was
      independently associated with a higher risk of metabolic syndrome (per 1 MUg/mL
      increase; odds ratio = 0.953, 95% confidence interval = 0.898-0.970, P < 0.001)
      after adjustment for multiple confounding factors. CONCLUSIONS:
      Hypoadiponectinemia is independently associated with the presence of metabolic
      syndrome in patients with chronic kidney disease.

PMID- 27895722
TI  - Deciphering fact from artifact when using reporter assays to investigate the
      roles of host factors on L1 retrotransposition.
AB  - BACKGROUND: The Long INterspersed Element-1 (L1, LINE-1) is the only autonomous
      mobile DNA element in humans and has generated as much as half of the genome. Due
      to increasing clinical interest in the roles of L1 in cancer, embryogenesis and
      neuronal development, it has become a priority to understand L1-host interactions
      and identify host factors required for its activity. Apropos to this, we recently
      reported that L1 retrotransposition in HeLa cells requires phosphorylation of the
      L1 protein ORF1p at motifs targeted by host cell proline-directed protein kinases
      (PDPKs), which include the family of mitogen-activated protein kinases (MAPKs).
      Using two engineered L1 reporter assays, we continued our investigation into the
      roles of MAPKs in L1 activity. RESULTS: We found that the MAPK p38delta
      phosphorylated ORF1p on three of its four PDPK motifs required for L1 activity.
      In addition, we found that a constitutively active p38delta mutant appeared to
      promote L1 retrotransposition in HeLa cells. However, despite the consistency of
      these findings with our earlier work, we identified some technical concerns
      regarding the experimental methodology. Specifically, we found that exogenous
      expression of p38delta appeared to affect at least one heterologous promoter in
      an engineered L1 reporter, as well as generate opposing effects on two different
      reporters. We also show that two commercially available non-targeting control
      (NTC) siRNAs elicit drastically different effects on the apparent
      retrotransposition reported by both L1 assays, which raises concerns about the
      use of NTCs as normalizing controls. CONCLUSIONS: Engineered L1 reporter assays
      have been invaluable for determining the functions and critical residues of L1
      open reading frames, as well as elucidating many aspects of L1 replication.
      However, our results suggest that caution is required when interpreting data
      obtained from L1 reporters used in conjunction with exogenous gene expression or
      siRNA.

PMID- 27895723
TI  - Cisplatin-induced regulation of signal transduction pathways and transcription
      factors in p53-mutated subclone variants of hepatoma cells: Potential application
      for therapeutic targeting.
AB  - Cisplatin is commonly recognized as a DNA-damaging drug; however, its versatile
      antitumor effects have been demonstrated to extend beyond this narrow functional
      attribute. The present study determined how cisplatin regulates alternative
      pathways and transcription factors to exert its additional antitumor actions.
      Cisplatin was observed to be able to trigger an endoplasmic reticulum stress
      response through aggravated nitrosative stress coupled to perturbed mitochondrial
      calcium (Ca2+) homeostasis, which substantially downregulated glucose-regulated
      protein (GRP) 78 expression by suppressing the cleavage of activating
      transcription factor (ATF) 6alpha (90 kDa) to its active 50 kDa subunit.
      Concomitantly, the ATF4-ATF3-C/emopamil binding protein homologous protein axis
      was activated by cisplatin, which triggered cellular glutathione (GSH) depletion
      by strongly inhibiting gamma-glutamylcysteine synthetase heavy chain (gamma
      GCSh), a key enzyme in GSH biosynthesis. The present study also demonstrated that
      cisplatin substantially inhibited beta-catenin, causing a marked downregulation
      of survivin and B-cell lymphoma (Bcl)-2. Taken together, the present results
      uncovered a novel mechanism of cisplatin that could simultaneously trigger the
      inhibition of three prominent antiapoptotic effector molecules (Bcl-2, survivin
      and GRP78) and effectively promote GSH depletion by inhibiting gamma-GCSh. These
      newly discovered functional attributes of cisplatin can provide an avenue for
      novel combined therapeutic strategies to kill hepatocellular carcinoma cells
      effectively.

PMID- 27895724
TI  - Expression profile of SPACA5/Spaca5 in spermatogenesis and transitional cell
      carcinoma of the bladder.
AB  - The majority of bladder cancer-associated mortalities are due to transitional
      cell carcinoma (TCC), which is the most prevalent and chemoresistant malignancy
      of the bladder. Sperm acrosome associated 5 (SPACA5)/Spaca5 is a sperm acrosome
      associated, c-type lysozyme-like protein that has been recently identified, and
      has been designated as an attractive candidate antigen for cancer testis. In the
      present study, the expression profile of SPACA5/Spaca5 was analyzed in
      spermatogenesis and TCC of the bladder using diverse molecular and cellular
      biology methods. Using reverse transcription-polymerase chain reaction (RT-PCR)
      to analyze the multi-tissue distribution and temporal expression of
      SPACA5/Spaca5, the SPACA5/Spaca5 gene was determined to be generally not
      expressed in normal tissue, with the exception of the testis, and it could be
      detected at a low level on day 20 after birth in mouse testes and at a higher
      level on day 28. Immunohistochemistry staining revealed that the SPACA5/Spaca5
      protein was exclusively observed in the elongated spermatid of the normal testes,
      and was ectopically expressed in the cytoplasm of TCC, while it was not expressed
      in normal bladder tissues. The frequency of SPACA5 messenger RNA was detected in
      45% of TCC (9/20) by RT-quantitative PCR. Furthermore, SPACA5 protein was more
      frequently detected in high-grade than in low-grade tumors (61.54 vs. 30.00%,
      P=0.035). Accordingly, high SPACA5 staining scores were observed to be
      significantly associated with high-grade tumors (n=65, R=0.279, P=0.027).
      Collectively, our findings indicated that SPACA5/Spaca5 may be important in male
      spermatogenesis and may be used as a potential target for specific immunotherapy
      in patients suffering from TCC.

PMID- 27895725
TI  - EHHM, a novel phenolic natural product from Livistona chinensis, induces
      autophagy-related apoptosis in hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) ranks the second cause of cancer-associated
      mortality worldwide. In the present study, the effects and mechanisms of a new
      phenolic natural product E-[6'-(5'-hydroxypentyl)tricosyl]-4-hydroxy-3
      methoxycinnamate (EHHM) isolated from Livistona chinensis on the growth of HCC
      cells were investigated. It was observed that EHHM treatment significantly
      suppressed cell proliferation and colony formation, and induced cell apoptosis
      via a mitochondria-dependent caspase pathway in HepG2 cells in a time- and dose
      dependent manner. Meanwhile, EHHM treatment also led to upregulated expression of
      autophagy protein 5 (Atg5), Beclin 1 and light chain 3 (LC3)-II proteins, and
      accumulation of green fluorescent protein-LC3 punctate florescent foci in HCC
      cells, suggesting that EHHM-induced apoptosis is accompanied by autophagy
      induction. Western blotting revealed that EHHM-induced autophagy is related to
      the inhibition of the Akt/mechanistic target of rapamycin/p70 ribosomal protein
      S6 kinase signaling pathway. Furthermore, treatment with Atg5 small interfering
      RNA or autophagy inhibitors significantly enhanced EHHM-mediated growth
      inhibition and apoptotic cell death, indicating that autophagy serves as a self
      protective mechanism in EHHM-treated HCC cells, and that combined treatment with
      EHHM and autophagy inhibitors may be an effective therapeutic strategy for HCC.

PMID- 27895726
TI  - Adenovirus-mediated interleukin 21 gene transfer enhances antitumor immunity and
      reduces tumorigenicity of Hepa1-6 in mice.
AB  - In the present study, adenovirus-mediated interleukin 21 (Ad5-IL-21-EGFP) gene
      expression was induced in Hepa1-6 cells to investigate whether IL-21 was capable
      of enhancing antitumor immunity and reducing tumorigenicity of Hepa1-6 in a mouse
      model. Mice were inoculated intradermally into the right flank with Hepa1-6 cells
      or Hepa1-6 cells infected with Ad5 or Ad5-IL-21. Four weeks later, the mice were
      sacrificed humanely, and the tumor volume, tumor weight and mouse spleen index
      were measured. The levels of IL-21, IL-4 and interferon (IFN)-gamma levels in
      mouse serum and tumor tissues were detected by enzyme-linked immunosorbent assay
      (ELISA) and immunohistochemistry. Cell counting kit-8 (CCK-8) assay was used to
      detect the killing ability of spleen T cells and natural killer (NK) cells, and
      the proliferation ability of T cells. The expression of IL-21 was confirmed by
      reverse transcription-polymerase chain reaction, western blot analysis and ELISA
      assay in Ad5-IL-21-EGFP-infected Hepa1-6 cells. The overexpression of IL-21
      significantly reduced the tumorigenicity of Hepa1-6 cells. The tumor volumes and
      tumor weights in Ad5-IL-21-Hepa1-6 mice were much smaller than those in the Ad5
      Hepa1-6 group and Hepa1-6 wild-type group. The immunohistochemistry and ELISA
      assay demonstrated that IL-21 and IFN-gamma levels were much higher while the IL
      4 level was much lower in the Ad5-IL-21-Hepa1-6 group than in the other two
      groups. CCK-8 assay revealed that the killing ability of NK cells and T cells,
      and the proliferation ability of T cells in Ad5-IL-21-Hepa1-6 mice were higher
      than in the other two groups; the spleen index of Ad5-IL-21-Hepa1-6 mice was also
      higher than in the other groups. The data had a significant difference (P<0.01).
      In conclusion, IL-21 reduces tumorigenicity of Hepa1-6 by a mechanism involving
      enhanced activation of cell-mediated immunity in tumor-bearing mice.

PMID- 27895727
TI  - Deficiency of SUMO-specific protease 1 induces arsenic trioxide-mediated
      apoptosis by regulating XBP1 activity in human acute promyelocytic leukemia.
AB  - Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a
      member of the SENP family, is highly expressed in several neoplastic tissues.
      However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been
      elucidated. In the present study, it was observed that SENP1 deficiency had no
      effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic
      trioxide (As2O3) could induce the upregulation of endoplasmic reticulum (ER)
      stress, resulting in the apoptosis of NB4 cells. Additionally, knockdown of SENP1
      significantly increased As2O3-induced apoptosis in NB4 cells transfected with
      small interfering RNA targeting SENP1. SENP1 deficiency also increased the
      accumulation of SUMOylated X-box binding protein 1 (XBP1), which was accompanied
      by the downregulation of the messenger RNA expression and transcriptional
      activity of the XBP1 target genes endoplasmic reticulum-localized DnaJ 4 and
      Sec61a, which were involved in ER stress and closely linked to the apoptosis of
      NB4 cells. Taken together, these results revealed that the specific de
      SUMOylation activity of SENP1 for XBP1 was involved in the ER stress-mediated
      apoptosis caused by As2O3 treatment in NB4 cells, thus providing insight into
      potential therapeutic targets for APL treatment via manipulating XBP1 signaling
      during ER stress by targeting SENP1.

PMID- 27895728
TI  - Quantitative contrast-enhanced ultrasonography for the differential diagnosis of
      endometrial hyperplasia and endometrial neoplasms.
AB  - The present study aimed to investigate the feasibility of applying contrast
      enhanced ultrasonography (CEUS) imaging technology for distinguishing between
      benign and malignant endometrial lesions, and to screen markers that could be
      correlated with the pathological results. In this study, endometrial diseases
      were diagnosed by biopsy under hysteroscopy and CEUS examinations. The intensity
      and time parameters of the time-intensity curve (TIC) were analyzed. The mean
      arrival time (AT), time-to-peak (TTP), rise time (RT), washout half-time and
      clearance half-time of malignant lesions were shorter than those of benign
      lesions (P<0.05), whereas the average peak intensity (PI) and enhancement
      intensity (EI) of malignant lesions were higher than those of benign lesions
      (P<0.05). The receiver operating characteristic curve showed the following cut
      off values: PI, 29.2 dB; EI, 21.35 dB; AT, 12.75 sec; TTP, 26.75 sec; RT, 13.2
      sec; clearance half-time, 89.3 sec; and washout half-time, 75.45 sec. The lesions
      with PI, an EI higher than that of the cut-off and lesions with an AT, TTP, RT,
      half clearing time and washout half-time shorter than the cut-off were considered
      malignant. The TTP, RT and half clearing time were negatively correlated with
      microvessel density (MVD), i.e., MVD was higher when the TTP, RT and half
      clearing time were shorter. Overall, changes in the enhancement and clearing of
      lesions could be quantitatively analyzed by CEUS TIC and further discriminate
      benign from malignant lesions. In the present study, CEUS appeared to indirectly
      reflect blood vessel changes inside the lesions and provided a pre-operative non
      invasive fast imaging method for the diagnosis of endometrial disease.

PMID- 27895729
TI  - Celastrus orbiculatus extract triggers apoptosis and autophagy via PI3K/Akt/mTOR
      inhibition in human colorectal cancer cells.
AB  - Celastrus orbiculatus is used as a folk medicine in China for the treatment of
      numerous diseases. The ethyl acetate extract of Celastrus orbiculatus (COE) also
      displays a wide range of anti-cancer activities in the laboratory. However, the
      effectiveness of COE-induced autophagy and its mechanism of action in colorectal
      cancer cells have not been investigated thus far. The present study analyzed the
      effect of COE on HT-29 cell viability, apoptosis and autophagy using MTT assay,
      flow cytometry, transmission electron microscopy and western blotting.
      Additionally, the autophagy inhibitor 3-methyladenine and the autophagy inducer
      rapamycin were used to further explore the effects of COE-induced autophagy in HT
      29 cells. The present study also examined whether the phosphatidylinositol-4,5
      bisphosphate 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70
      ribosomal protein S6 kinase (p70S6K) signaling pathway was involved in the
      regulation of COE-induced autophagy. The results revealed that COE inhibited HT
      29 cell proliferation and decreased cell survival in a time- and dose-dependent
      manner, and that COE possessed the ability to induce both apoptosis and autophagy
      in HT-29 cells. Furthermore, autophagy and apoptosis induced by COE synergized to
      inhibit colorectal cancer growth. In addition, COE treatment decreased the
      phosphorylation of Akt and its downstream effectors mTOR and p70S6K. Taken
      together, these results demonstrate that both autophagy and apoptosis were
      activated during COE treatment of HT-29 cells, and that COE-induced autophagy
      decreases the viability of HT-29 cells via a mechanism that may depend on the
      PI3K/Akt/mTOR/p70S6K signaling pathway. Furthermore, compounds that induce
      autophagy administered in combination with COE may be an attractive strategy for
      enhancing the anti-tumor potency of COE in colorectal cancer.

PMID- 27895730
TI  - Osthole induces lung cancer cell apoptosis through inhibition of inhibitor of
      apoptosis family proteins.
AB  - In the present study, we investigated the effects and mechanisms of Osthole on
      the apoptosis of non-small cell lung cancer (NSCLC) cells and its synergistic
      effect with Embelin. Our results revealed that treatment with both Osthole and
      Embelin inhibited cell proliferation. Notably, combination treatment of Osthole
      and Embelin inhibited cell proliferation more significantly compared with
      monotherapy. In addition, morphological analysis and Annexin V/propidium iodide
      analysis revealed that the combination of Osthole and Embelin enhanced their
      effect on cell apoptosis. We further examined the effect of Osthole on the
      expression of inhibitor of apoptosis protein (IAP) family proteins. That
      treatment of A549 lung cancer cells with various concentrations of Osthole was
      observed to decrease the protein expression of X-chromosome-encoded IAP, c-IAP1,
      c-IAP2 and Survivin, and increase Smac expression in a dose-dependent manner.
      Furthermore, it was noted that Osthole or Embelin alone increased the expression
      of BAX, caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9, and
      decreased Bcl-2 levels following treatment. Osthole and Embelin combination
      treatment had a synergistic effect on the regulation of these proteins. In
      conclusion, our study demonstrated that Osthole inhibited proliferation and
      induced the apoptosis of lung cancer cells via IAP family proteins in a dose
      dependent manner. Osthole enhances the antitumor effect of Embelin, indicating
      that combination of Osthole and Embelin has potential clinical significance in
      the treatment of NSCLC.

PMID- 27895732
TI  - Effect of matrine combined with cisplatin on the expression of XIAP in human
      rhabdomyosarcoma RD cells.
AB  - The combined effects of matrine (Mat) and cisplatin on the survival and apoptosis
      of rhabdomyosarcoma (RMS) RD cells, as well as the possible mechanism of the
      synergistic effect of Mat and cisplatin were investigated in the present study.
      RMS RD cells were divided and treated as follows: control group, 5 mg/l cisplatin
      group, Mat groups (0.5, 1.0 and 1.5 g/l), and Mat (0.5, 1.0 and 1.5 g/l) combined
      with 5 mg/l cisplatin groups. An MTT assay and flow cytometry were applied to
      detect the survival and apoptotic rates, respectively, while RT-PCR was applied
      to detect the expression levels of X-linked inhibitor of apoptosis protein (XIAP)
      mRNA in the RD cells of each group. The survival rates of RD cells in each
      experimental group were lower than in the control group, and the apoptotic rates
      were higher than those in the control group (P<0.05). An increase in drug
      concentrations led to the cell proliferation inhibitory and apoptotic rates of
      the single Mat groups increasing as a function of dose (pairwise comparison among
      the groups, P<0.05), while the proliferation inhibitory and apoptotic rates of
      Mat combined with the cisplatin groups under different concentration were
      significantly higher than those of the single Mat and single cisplatin groups
      under the same concentration (P<0.01). The expression levels of XIAP mRNA in the
      RD cells of each experimental group were lower than those in the control group
      (P<0.05). Additionally, the expression levels of XIAP mRNA in the group treated
      with Mat and cisplatin were significantly lower than those of the single
      cisplatin and single Mat groups (P<0.01). In conclusion, Mat and cisplatin are
      capable of inhibiting the proliferation of RD cells and inducing apoptosis by
      suppressing the XIAP mRNA expression levels.

PMID- 27895733
TI  - Improved laparoscopic nephron-sparing surgery for renal cell carcinoma based on
      the precise anatomy of the nephron.
AB  - The aim of the present study was to investigate a method of laparoscopic nephron
      sparing surgery (LNSS) for renal cell carcinoma (RCC) based on the precise
      anatomy of the nephron, and to decrease the incidence of hemorrhage and urinary
      leakage. Between January 2012 and December 2013, 31 patients who presented to the
      General Hospital of the People's Liberation Army (Beijing, China) were treated
      for RCC. The mean tumor size was 3.4+/-0.7 cm in diameter (range, 1.2-6.0 cm).
      During surgery, the renal artery was blocked, and subsequently, an incision in
      the renal capsule and renal cortex was performed, at 3-5 mm from the tumor edge.
      Subsequent to the incision of the renal parenchyma, scissors with blunt and sharp
      edge were used to separate the base of the tumor from the normal renal medulla,
      in the direction of the ray medullary in the renal pyramids. The basal blood
      vessels were incised following the hemostasis of the region using bipolar
      coagulation. The minor renal calyces were stripped carefully and the wound was
      closed with an absorbable sutures. The arterial occlusion time, duration of
      surgery, intraoperative bleeding volume, post-operative drainage volume,
      pathological results and complications were recorded. The surgery was successful
      for all patients. The estimated average intraoperative bleeding volume was 55.7
      ml, the average surgical duration was 95.5 min, the average arterial occlusion
      time was 21.2 min, the average post-operative drainage volume was 92.3 ml and the
      average post-operative length of hospital stay was 6.1 days. No hemorrhage or
      urinary leakage was observed in the patients following the surgery. LNSS for RCC
      based on the precise anatomy of the nephron was concluded to be effective and
      feasible. The surgery is useful for the complete removal of tumors and guarantees
      a negative margin, which may also decrease the incidence of hemorrhage and
      urinary leakage following surgery.

PMID- 27895731
TI  - Advantages and disadvantages of F-18 fluorodeoxyglucose positron emission
      tomography/computed tomography in carcinoma of unknown primary.
AB  - Carcinoma of unknown primary is a type of malignant disease where the primary
      carcinoma cannot be identified by conventional examination, which presents
      challenges in diagnosis and therapy. This study aims to evaluate the detailed
      clinical value and indications of using fluorine-18-2-fluoro-2-deoxy-D-glucose
      positron emission tomography/computed tomography (F-18 FDG PET/CT) in a large
      sample. A total of 449 patients who were selected under strict standards were
      retrospectively included in this study. F-18 FDG PET/CT accurately detected the
      primary carcinoma in 115 of 449 patients whose primaries could not be detected by
      conventional examination (25.6%), with additional 27 false-positive patients. The
      most common primary site was the lung (34.8%). In addition, except for in
      metastatic melanoma (1/19, 5.3%) and axillary metastasis patients (2/49, 4.1%), F
      18 FDG PET/CT had a comparative performance in detecting primary carcinoma in
      other pathological types and anatomical locations. The scan is able to guide
      treatment strategy modifications to some extent (130/449, 29.0%). We strongly
      recommend the use of F-18 FDG PET/CT in the early phase of examination. It is
      also recommended as a supplementary radiological method, and certain patients may
      benefit from its application in cases where regular examination is inconclusive.
      However, in metastatic melanoma or axillary metastasis patients where the primary
      site cannot be identified by routine examination, regular application of F-18 FDG
      PET/CT for the sole purpose of detecting the primary carcinoma should not be
      encouraged.

PMID- 27895734
TI  - Periostin and tumor-stroma interactions in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer
      associated mortality globally. Interactions of the cancer cells with the tumor
      microenvironment are essential carcinogenic features for the majority of solid
      tumors, such as pancreatic cancer. The present study investigated the role of
      stromal activation in NSCLC and analyzed the surgical specimens of 93 patients by
      immunohistochemistry with regard to periostin (an extracellular matrix protein),
      alpha-smooth muscle actin (alpha-SMA; a marker of myofibroblasts) and cluster of
      differentiation 31 (CD31; a marker of endothelial cells), and the activated
      stroma index. There was a trend towards reduced overall survival for patients
      with high periostin expression (hazard ratio, 1.80; 95% confidence interval, 0.99
      3.27; P=0.050). No significant correlations with overall survival were identified
      for alpha-SMA (P=0.930), CD31 (P=0.923), collagen (P=0.441) or the activated
      stroma index (P=0.706). In a multivariable analysis, the histological tumor
      subtype, tumor stage, lymph node involvement and resection status were
      independent prognostic factors in NSCLC, but none of the investigated
      immunohistochemical markers were prognostic factors. Thus, the tumor
      microenvironment and stroma activation did not prove to be of prognostic
      relevance for lung cancer, as it has been previously described for pancreatic
      cancer. Other markers of the microenvironment of NSCLC may be of higher
      prognostic value, pointing towards tumor-type specific effects.

PMID- 27895735
TI  - Crk-like adapter protein is overexpressed in cervical carcinoma, facilitates
      proliferation, invasion and chemoresistance, and regulates Src and Akt signaling.
AB  - Overexpression of Crk-like (CrkL) adapter protein has been implicated in a number
      of types of human cancer. However, its involvement in human cervical carcinoma
      remains unclear. The present study aimed to explore the clinical significance and
      biological characteristics of CrkL in human cervical carcinoma. CrkL protein
      expression was examined in tissue samples from 92 cases of cervical carcinoma
      using immunohistochemistry, and was found to be overexpressed in 48.9% (45/92
      cases). CrkL was transfected into HeLa and CaSki cervical carcinoma cell lines
      and its effects on biological behavior were examined. CrkL overexpression was
      revealed to promote cell proliferation, invasion and chemoresistance. In
      addition, CrkL overexpression increased the level of Src and Akt phosphorylation.
      Treatment with the Src inhibitor dasatinib eliminated the effect of CrkL on cell
      invasion. In conclusion, the current results demonstrate that CrkL is an
      oncoprotein overexpressed in cervical carcinoma which contributes to malignant
      cell growth and chemoresistance. In addition, the findings indicate that CrkL
      promotes cervical cancer cell invasion through a Src-dependent pathway.

PMID- 27895736
TI  - Effect of silencing SATB1 on proliferation, invasion and apoptosis of A549 human
      lung adenocarcinoma cells.
AB  - The present study aimed to explore the clinical characteristics of special
      adenine-thymine-rich sequence-binding protein 1 (SATB1) in lung adenocarcinoma
      and its role in the proliferation, invasion, migration and apoptosis of the lung
      adenocarcinoma cell line A549. The expression of SATB1 was first studied in tumor
      tissues of lung adenocarcinoma and adjacent non-tumor tissues. The siRNA green
      fluorescent protein expression vector of SATB1 was constructed and transfected
      into the lung adenocarcinoma cell line A549, then a fluorescence microscope was
      used to study the transfection efficiency. Western blot analysis was adopted to
      measure the silencing efficiency. 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT), Transwell and scratch assays were used to
      study cell proliferation, invasion and migration activity, and the apoptosis rate
      was tested by flow cytometry. SATB1 expression was low in the adjacent non-tumor
      tissues but high in lung adenocarcinoma tissues, and it was reversely
      proportional to the differentiation degree. Following transfection with SATB1
      siRNA, the expression of SATB1 in A549 cells was blocked (P<0.01). In addition,
      the proliferation, invasion and migration abilities of cells decreased
      significantly while the apoptosis rate increased significantly (P<0.01). In
      conclusion SATB1 is closely associated with the pathogenesis and development of
      lung adenocarcinoma.

PMID- 27895737
TI  - High PARP-1 expression is associated with tumor invasion and poor prognosis in
      gastric cancer.
AB  - Poly (adenosine diphosphate-ribose) polymerase 1 (PARP-1) was previously
      demonstrated to be overexpressed in numerous malignant tumors and associated with
      invasiveness and poor prognosis. However, the expression of the PARP-1 protein in
      gastric cancer and its association with clinical outcomes requires further
      investigation. In the present study, the expression of PARP-1 in 564 gastric
      cancer tissues and 335 tumor-adjacent control tissues is investigated, using
      tissue microarray-based immunohistochemistry. PARP-1 expression levels were
      demonstrated to be significantly higher in gastric cancer tissue samples, as
      compared with control tissue samples. In gastric cancer, high PARP-1 expression
      levels were significantly associated with Helicobacter pylori (H. pylori)
      infection (P=0.032), decreased differentiation (P<0.001), increased depth of
      invasion (P=0.037), presence of lymphatic invasion (P<0.001), presence of lymph
      node metastasis (P<0.001), and advanced tumor-node-metastasis (TNM) stage
      (P=0.015). High PARP-1 expression levels were associated with a significantly
      shorter overall survival rate (P<0.001) and disease-free survival rate (P=0.001)
      in patients with gastric cancer, particularly a subset of patients with H. pylori
      infection or an advanced TNM stage. In addition, univariate analysis indicated
      that PARP-1 high expression levels were significantly associated with a poor
      prognosis in gastric cancer. These results suggest that PARP-1 expression may be
      involved in the progression and prognosis of gastric cancer, particularly H.
      pylori-positive or advanced-stage gastric cancer.

PMID- 27895738
TI  - Cyclooxygenase-2 is associated with malignant phenotypes in human lung cancer.
AB  - The objective of the present study was to investigate whether cyclooxygenase-2
      (COX-2) is associated with malignancy, and to investigate its molecular
      mechanisms in human lung cancer tumor malignancy. The present study used RNA
      interference (RNAi) methodology and celecoxib, a COX-2 inhibitor, to investigate
      the effect of COX-2 knockdown on the proliferation and invasion abilities of lung
      cancer cells and the molecular mechanisms involved. Human lung adenocarcinoma
      A549-si10 and LTEP-A2 cells transfected with a specific small interfering RNA
      (A549-si10 and LTEP-A2-si10, respectively) grew more slowly compared with
      parental cell lines and cells transfected with pU6. The colony formation of A549
      si10 and LTEP-A2-si10 cells was also reduced. In addition, A549-si10 and LTEP-A2
      si10 cells were characterized by decreased metastatic and invasive abilities. The
      proliferation and invasive potential of parental A549 and LTEP-A2 cells was
      inhibited following treatment with celecoxib. In vivo, a COX-2 knockdown resulted
      in a decrease of proliferation and reduction of vascular endothelial growth
      factor (VEGF), matrix metalloproteinase-2 (MMP-2) and endothelial growth factor
      receptor (EGFR) expression in A549 xenografts. In conclusion, the present study
      revealed that COX-2 plays a extremely important role in tumor growth,
      infiltration and metastasis via the regulation of VEGF, MMP-2 and EGRF
      expression. Therefore, COX-2 is a potential therapeutic target for lung cancer.

PMID- 27895740
TI  - Letrozole as second-line hormonal treatment for recurrent low-grade endometrial
      stromal sarcoma: A case report and review of the literature.
AB  - Low-grade endometrial stromal sarcoma (LGESS) is a rare malignancy. The tumor is
      reportedly responsive to hormonal therapy, most commonly with medroxyprogesterone
      acetate (MPA), but the effectiveness of aromatase inhibitors for recurrent LGESS
      remains unclear. The present study reports a case of stage IC LGESS presenting
      with abnormal uterine bleeding, and also provides a review of the literature.
      Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, MPA
      therapy was initiated; treatment was successful, but discontinued 19 months later
      due to disruptive side effects. A further 2 months later, the patient presented
      with recurrent disease and received chemotherapy. MPA treatment was restarted
      with a partial response. A second recurrence, 4 years later, presented with lung
      and para-aortic lymph node metastases. The patient responded to treatment with
      the aromatase inhibitor letrozole. The patient has since exhibited stable disease
      and remained free of symptoms for 7 years. This case suggests that aromatase
      inhibitor treatment may be effective for recurrent LGESS as a second-line
      treatment.

PMID- 27895739
TI  - Gene expression profiling of the 8q22-24 position in human breast cancer: TSPYL5,
      MTDH, ATAD2 and CCNE2 genes are implicated in oncogenesis, while WISP1 and EXT1
      genes may predict a risk of metastasis.
AB  - Gene expression profiling has been suggested to predict breast cancer outcome.
      The prognostic value of the 8q22-24 position in breast cancer remains to be
      elucidated. The present study evaluated expression patterns of the genes located
      at this position in metastatic and non-metastatic breast cancer. A total of 85
      patients with recurrent/metastatic (n=15) and non-metastatic (n=70) early-stage,
      estrogen receptor-positive and lymph node-negative breast tumors were included.
      In addition, 15 normal breast tissue samples were used as controls. Demographic
      and clinical features were recorded. Subsequently, mRNA copy numbers of exostosin
      glycosyltransferase 1 (EXT1), WNT1 inducible signaling pathway protein 1 (WISP1),
      ATPase family, AAA domain containing 2 (ATAD2), TSP-like 5 (TSPYL5), metadherin
      (MTDH) and cyclin E2 (CCNE2) genes were measured by reverse transcription
      quantitative polymerase chain reaction assay. The expression of EXT1 and WISP1
      exhibited a significant decline in the metastatic breast cancer group compared to
      the control (P=0.015 and P=0.012, respectively). The expression of TSPYL5, MTDH
      and ATAD2 was significantly decreased in the metastatic (P=0.002, P=0.018 and
      P=0.016, respectively) and non-metastatic (P=0.038, P=0.045 and P=0.000,
      respectively) breast cancer groups compared with the control. The expression of
      CCNE2 in the metastatic and non-metastatic breast cancer groups was significantly
      increased compared with the control (P=0.002 and P=0.001, respectively). WISP1
      expression demonstrated a correlation with patient age and tumor size, and TSPYL5
      expression was correlated with lymphovascular invasion. None of the genes
      investigated exhibited any correlation with stage and grade of disease. The
      TSPYL5, MTDH, ATAD2 and CCNE2 genes may be implicated in the pathogenesis of
      human breast cancer, while the WISP1 and EXT1 genes may have the potential to
      serve as promising indicators of the risk of metastasis. However, further studies
      are required to validate these results.

PMID- 27895741
TI  - The prognostic significance of estrogen receptor beta in head and neck squamous
      cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in
      the world. Although multimodal and targeted therapy is now used in therapeutic
      procedures, the survival of patients with HNSCC has remained unchanged over the
      last 30 years. A number of studies have demonstrated that the increased
      expression of intranuclear ERbeta in breast, lung and colon cancer is a favorable
      prognostic marker associated with higher survival rates. However, the clinical
      significance of sex hormone receptors in HNSCC remains unclear. The current study
      aimed to assess the expression of ERbeta in HNSCC immunohistochemically and
      investigate any possible association between ERbeta expression, and clinical and
      histopathological factors, disease recurrence and patient survival. The present
      study included 174 patients (165 males and 9 females) with a median age of 60.8
      years (range, 39-79) with HNSCC who were primary surgically treated between
      January 2000 and December 2006. Immunohistochemical reactions for ERbeta
      demonstrated that 73 patients (42%) exhibited positive ERbeta expression.
      Distribution of ERbeta status among different head and neck subsites indicated
      that >40% of all negative cases were located in laryngeal primaries, while
      incidence of other sublocalization within positive cases was similar and
      comparable (P=0.04). Furthermore, a correlation was observed between ERbeta
      immunopositivity and the survival of patients, with respect to the primary tumor
      site. Patients with ERbeta positive oropharyngeal cancer had a survival rate of
      35.3% at 5-years compared with 25% for patients with negative expression.
      However, ERbeta status was not significantly correlated with any other clinical
      or histopathological parameter. After an average follow-up time of 38.5 months
      (range, 3-60 months), 54 patients (31.1%) had succumbed to disease recurrence
      while 50 (28.7%) succumbed to other causes. In conclusion, ERbeta positivity
      indicates improved survival of patients with oropharyngeal cancer. Further
      research is required in order to implement novel therapeutic strategies.

PMID- 27895742
TI  - Comparative analysis of gene expression profiles of gastric cardia adenocarcinoma
      and gastric non-cardia adenocarcinoma.
AB  - In the present study, gene expression profiles were analyzed to identify the
      molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric
      non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number
      GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA
      samples and 62 normal controls, as well as 72 GNCA samples and 72 normal
      controls. The two groups of differentially-expressed genes (DEGs) were compared
      to obtain common and unique DEGs. A differential analysis was performed using the
      Linear Models for Microarray Data package in R. Functional enrichment analysis
      was conducted for the DEGs using the Database for Annotation, Visualization and
      Integrated Discovery. Protein-protein interaction (PPI) networks were constructed
      for the DEGs with information from the Search Tool for the Retrieval of
      Interacting Genes. Subnetworks were extracted from the whole network with
      Cytoscape. Compared with the control, 284 and 268 genes were differentially
      expressed in GCA and GNCA, respectively, of which 194 DEGs were common between
      GCA and GNCA. Common DEGs [e.g., claudin (CLDN)7, CLDN4 and CLDN3] were
      associated with cell adhesion and digestion. GCA-unique DEGs [e.g., MAD1 mitotic
      arrest deficient like 1, cyclin (CCN)B1, CCNB2 and CCNE1] were associated with
      the cell cycle and the regulation of cell proliferation, while GNCA-unique DEGs
      (e.g., GATA binding protein 6 and hyaluronoglucosaminidase 1) were implicated in
      cell death. A PPI network with 141 nodes and 446 edges were obtained, from which
      two subnetworks were extracted. Genes [e.g., fibronectin 1, collagen type I
      alpha2 chain (COL1A2) and COL1A1] from the two subnetworks were implicated in
      extracellular matrix organization. These common DEGs could advance our
      understanding of the etiology of gastric cancer, while the unique DEGs in GCA and
      GNCA could better define the properties of specific cancers and provide potential
      biomarkers for diagnosis, prognosis or therapy.

PMID- 27895743
TI  - Diagnosis of pancreatic lesions collected by endoscopic ultrasound-guided fine
      needle aspiration using next-generation sequencing.
AB  - Endoscopic ultrasound-guided fine-needle aspiration (EUF-FNA) has improved the
      diagnosis of pancreatic lesions. Next-generation sequencing (NGS) facilitates the
      production of millions of sequences concurrently. Therefore, in the current
      study, to improve the detectability of oncogenic mutations in pancreatic lesions,
      an NGS system was used to diagnose EUS-FNA samples. A total of 38 patients with
      clinically diagnosed EUS-FNA specimens were analyzed; 27 patients had pancreatic
      ductal adenocarcinoma (PDAC) and 11 had non-PDAC lesions. DNA samples were
      isolated and sequenced by NGS using an Ion Personal Genome Machine system. The
      Cancer Hotspot Panel v2, which includes 50 cancer-related genes and 2,790 COSMIC
      mutations, was used. A >2% mutation frequency was defined as positive. KRAS
      mutations were detected in 26 of 27 PDAC aspirates (96%) and 0 of 11 non-PDAC
      lesions (0%). The G12, G13, and Q61 KRAS mutations were found in 25, 0, and 1 of
      the 27 PDAC samples, respectively. Mutations were confirmed by TaqMan(r)
      polymerase chain reaction analysis. TP53 mutations were detected in 12 of 27 PDAC
      aspirates (44%). SMAD4 was observed in 3 PDAC lesions and cyclin-dependent kinase
      inhibitor 2A in 4 PDAC lesions. Therefore, the current study was successfully
      able to develop an NGS assay with high clinical sensitivity for EUS-FNA samples.

PMID- 27895744
TI  - Identification of targets of miRNA-221 and miRNA-222 in fulvestrant-resistant
      breast cancer.
AB  - The present study aimed to identify the differentially expressed genes (DEGs)
      regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the
      resistance of breast cancer to fulvestrant. The GSE19777 transcription profile
      was downloaded from the Gene Expression Omnibus database, and includes data from
      three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR
      breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant
      resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent
      protein)-treated fulvestrant-resistant MCF7-FR cells. The linear models for
      microarray data package in R/Bioconductor was employed to screen for DEGs in the
      miRNA-transfected cells, and the pheatmap package in R was used to perform two
      way clustering. Pathway enrichment was conducted using the Gene Set Enrichment
      Analysis tool. Furthermore, a miRNA-messenger (m) RNA regulatory network
      depicting interactions between miRNA-targeted upregulated DEGs was constructed
      and visualized using Cytoscape. In total, 492 and 404 DEGs were identified for
      the antisense miRNA-221-transfected MCF7-FR cells and the antisense miRNA-222
      transfected MCF7-FR cells, respectively. Genes of the pentose phosphate pathway
      (PPP) were significantly enriched in the antisense miRNA-221-transfected MCF7-FR
      cells. In addition, components of the Wnt signaling pathway and cell adhesion
      molecules (CAMs) were significantly enriched in the antisense miRNA-222
      transfected MCF7-FR cells. In the miRNA-mRNA regulatory network, miRNA-222 was
      demonstrated to target protocadherin 10 (PCDH10). The results of the present
      study suggested that the PPP and Wnt signaling pathways, as well as CAMs and
      PCDH10, may be associated with the resistance of breast cancer to fulvestrant.

PMID- 27895745
TI  - Evaluation of the association between HIF-1alpha and HER-2 expression, hormone
      receptor status, Ki-67 expression, histology and tumor FDG uptake in breast
      cancer.
AB  - The present study aimed to examine hypoxia-inducible factor (HIF)-1alpha
      expression and its association with glucose uptake in invasive breast cancer. In
      addition, connections between glucose uptake and several other prognostic
      parameters of breast cancer were studied. Between August 2013 and April 2015, 92
      patients with biopsy-diagnosed breast cancer were subjected to 18F
      fluorodeoxyglucose positron emission tomography/computed tomography. The primary
      tumor and nodal maximum standardized uptake values (SUVmax) were recorded, and
      HIF-1alpha expression and clinical parameters, including tumor mass, estrogen
      receptor (ER) and progesterone receptor (PgR) levels, human epidermal growth
      factor receptor-2 (HER-2), Ki-67 index, grade and histology, were analyzed.
      SUVmax was compared with clinicopathological parameters and HIF-1alpha
      expression. The median SUVmax values of the ER-negative and PgR-negative tumors
      were significantly increased compared with ER and PgR-positive tumors,
      respectively (P=0.004 and P=0.008). SUVmax differed significantly between the T2
      and T3 tumors and the T1 tumors. The median SUVmax levels were higher in the Ki
      67 expression >10% group than the Ki-67 index <10% group (P=0.001). Although the
      median SUVmax values in HER-2-positive and -negative tumors were similar, triple
      negative tumors demonstrated significantly higher values (P=0.04). With regard to
      tumor grade, the median SUVmax was greater in the high-grade tumors compared with
      the low-grade tumors. SUVmax did not exhibit a significant correlation with HIF
      1alpha expression; however, HIF-1alpha expression was associated with tumor size
      and PgR expression. HIF-1alpha expression increased with a larger tumor size
      (r=0.27; P=0.008) and decreased PgR expression (r=-0.26; P=0.0002). The axillary
      nodal SUVmax of the N1 tumors was significantly lower than the N2 and N3 tumors
      (P<0.0001). In the multivariate analysis, tumor size, Ki-67 expression and ER
      Allred score were independent factors that impacted SUVmax. The results of the
      present study indicated strong associations between tumor size, tumor grade, Ki
      67 expression, triple-negativity, downregulated hormone receptor expression and
      SUVmax values. Conversely, there was no association observed between glucose
      uptake and levels of HIF-1alpha. Based on these results, it is suggested that the
      lack of assiocation between hypoxia and glucose uptake indicates phenotypic
      independence.

PMID- 27895746
TI  - RNAi-mediated gene silencing of vascular endothelial growth factor C suppresses
      growth and induces apoptosis in mouse breast cancer in vitro and in vivo.
AB  - Vascular endothelial cell growth factor (VEGF)-C promotes tumorigenesis by
      allowing lymph node metastasis and lymphangiogenesis, among other actions. RNA
      interference (RNAi) is a novel technique for suppressing target gene expression
      and may increase the effectiveness of cancer treatments. The present study
      assessed the influence of VEGF-C RNAi on the apoptosis and proliferation of mouse
      breast cancer cells in vitro and in vivo. A total of three pairs of small
      interfering RNA (siRNA) targeting mouse VEGF-C were designed and synthesized
      prior to transfection into 4T1 cells via a liposomal approach. Reverse
      transcription polymerase chain reaction, western blot analysis, a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Hoechst 33258
      staining and flow cytometry were performed in vitro to analyze VEGF-C expression,
      cleaved caspase-3 protein expression and 4T1 cell proliferation and apoptosis.
      Experiments were also conducted in vivo on BALB/c mice with breast cancer. Tumor
      weight and volume were measured and the number of apoptotic cells in tumor
      tissues was assessed by a TUNEL assay. Immunohistochemical assays and an enzyme
      linked immunosorbent assay were used to measure the expression of VEGF-C in tumor
      tissues. The results demonstrated that the three pairs of siRNA, particularly
      siV2, significantly reduced VEGF-C mRNA and protein levels in 4T1 cells. siV2 was
      deemed to be the most efficient siRNA and therefore was selected to be used in
      subsequent experiments. Furthermore, in vitro studies indicated that VEGF-C RNAi
      significantly decreased cell growth, induced apoptosis and upregulated the
      expression of cleaved caspase-3 protein. Tumor weight and volume in breast cancer
      in vivo models was reduced by the intratumoral injection of siV2. Antitumor
      efficacy was associated with decreased VEGF-C expression and increased induction
      of apoptosis. The present study therefore indicated that VEGF-C RNAi inhibited
      mouse breast cancer growth in vitro and in vivo and that it may be a novel
      targeted therapy for breast cancer.

PMID- 27895748
TI  - Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma.
AB  - In order to determine whether microRNA (miR)-300 is a diagnostic and prognostic
      biomarker in osteosarcoma, the miR-300 levels in serum of 114 osteosarcoma
      patients and 114 healthy controls were compared, followed by serum analysis of
      the differences between the pre-operative and post-operative sera of these
      osteosarcoma patients. It was observed that the concentration levels of miR-300
      in the serum of osteosarcoma patients was significantly higher than those in the
      serum of healthy controls (P<0.01). Furthermore, the concentration levels of miR
      300 in the post-operative serum were significantly reduced when compared with the
      pre-operative serum levels (P<0.001). High miR-300 levels in serum correlated
      significantly with clinical stage, distant metastasis and poor survival of
      osteosarcoma patients. Notably, serum miR-300 was an independent prognostic
      marker for osteosarcoma. In conclusion, our results suggested that serum miR-300
      may be a potential and useful noninvasive biomarker for the early detection of
      osteosarcoma.

PMID- 27895747
TI  - Overexpression of microRNA-24 increases the sensitivity to paclitaxel in drug
      resistant breast carcinoma cell lines via targeting ABCB9.
AB  - Paclitaxel has been widely used in the treatment of breast cancer. However, the
      development of drug resistance often increases the failure of chemotherapy.
      Growing evidence has reported the significant role of microRNAs (miRs) in drug
      resistance. The present study identified that miR-24 was significantly
      downregulated in paclitaxel-resistant (PR) breast cancer patients and in MCF-7/PR
      human breast carcinoma cells, and that overexpression of miR-24 could increase
      the effect of paclitaxel on drug-resistant breast carcinoma cells. Furthermore,
      miR-24 could directly bind to the 3'-untranslated region of ATP binding cassette
      B9 to downregulate its expression, thereby reducing drug transportation and
      improving the anti-tumor effect of paclitaxel on breast cancer cells. In vivo
      experiments also demonstrated that overexpression of miR-24 could increase the
      sensitivity of drug-resistant MCF-7 cells to paclitaxel. In conclusion, the
      present results suggested a novel function for miR-24 in reducing paclitaxel
      resistance in breast cancer, which may be of important clinical significance.

PMID- 27895749
TI  - A single-center retrospective study of pediatric hepatoblastoma.
AB  - Hepatoblastoma is a malignant liver tumor generally diagnosed in infants and
      children <3 years old. The current retrospective study aimed to investigate the
      associations of tumor stage, pathological type, metastasis and chemotherapy with
      clinical outcomes. In the current study, a total of 102 patients with
      hepatoblastoma were enrolled between September 2006 and June 2014. Clinical
      records and follow-up information for each of patient were obtained to conduct a
      Kaplan-Meier survival analysis and log-rank test. The median age of the subjects
      was 1.5 years, and 98 patients had stage III or IV hepatoblastoma. Complete or
      partial remittance occurred in 72 subjects, and 91 underwent surgical operation.
      The survival rate differed significantly among patients with different tumor
      stages (P=0.015, chi2=8.359). The mortality rate of stage IV subjects with
      intrahepatic metastasis was significantly higher than that of those without
      (P=0.004). Among the 45 subjects with relapsed hepatoblastoma, the mortality rate
      was higher in the subjects that abandoned chemotherapy than in patients who
      continued regular chemotherapy. In total, 27 of 45 subjects with relapsed
      hepatoblastoma succumbed to the disease; 20 of them abandoned chemotherapy
      treatment; and the remaining 7 patients underwent regular chemotherapy and
      succumbed to the disease by the end of follow-up. The present study indicates
      that the increased mortality rate was associated with postoperative residual
      induced intrahepatic metastasis and relapsed hepatoblastoma; and that regular
      chemotherapy is necessary for patient to achieve complete or partial remission
      following surgical operation.

PMID- 27895750
TI  - MicroRNA-298 inhibits malignant phenotypes of epithelial ovarian cancer by
      regulating the expression of EZH2.
AB  - MicroRNA (miRNA or miR)-298 has been reported to be downregulated and to modify
      the expression of the polycomb protein enhancer of zeste 2 (EZH2) in recurrent
      epithelial ovarian cancer (EOC). To date, no functional evidence of a miR-298
      EZH2 axis in EOC has been documented. The present study aimed to investigate the
      associations of miR-298 and/or EZH2 expression with clinicopathological features
      of EOC patients, and revealed their roles in cell motility based on EOC cell
      lines. Reverse transcription-quantitative polymerase chain reaction was performed
      to detect the expression levels of miR-298 and EZH2 messenger RNA in human EOC
      tissues and cell lines. Wound healing and transwell assays were performed to
      determine the function of the miR-298-EZH2 axis on cell migration and invasion,
      respectively. Compared with normal tissues, miR-298 expression was significantly
      downregulated, while EZH2 expression was significantly upregulated, in human EOC
      tissues (both P=0.001). In addition, miR-298 downregulation and EZH2 upregulation
      were significantly associated with high clinical stage (both P=0.01) and
      pathological grade (both P=0.02) of EOC patients. Furthermore, the ectopic
      expression of miR-298 could efficiently inhibit cell migration and invasion.
      Notably, the overexpression of EZH2 could restore the cell migration and invasion
      abilities suppressed by miR-298. Our data offer convincing evidence that the
      dysregulation of the miR-298-EZH2 axis may be important in tumor progression of
      EOC patients. The present study also confirmed a tumor-suppressive role of miR
      298 in modulating EOC cell motility by regulating the expression of EZH2,
      implying its potential as a novel miRNA-based therapeutic target for the
      treatment of human EOC.

PMID- 27895751
TI  - Value of window technique in diagnosis of the ground glass opacities in patients
      with non-small cell pulmonary cancer.
AB  - The aim of the present study was to examine the value of window technique in
      qualitative diagnosis of the ground glass opacities (GGO) in patients with non
      small cell pulmonary cancer. A total of 124 clinically suspected pulmonary cancer
      patients were analyzed retrospectively. The lesions were affirmed by puncture
      biopsy, and were GGO on pulmonary window while were invisible on mediastinal
      window. Sixty-four multi-detector spiral computed tomography with the window
      width and window level of 1,500 Hounsfield units (HU) and -450 HU on pulmonary
      window, while the window width and window level of 400 and 40 HU on mediastinal
      window, was used in the study. The window adjustment technique was used to
      analyze the window width and window level of lesion on pulmonary window and
      mediastinal window, for searching invisible threshold on 3-megapixel medical
      displays. The diagnostic accuracy and the cut-off value were compared on receiver
      operating characteristic (ROC) curve. The results showed that the window width
      and window level on pulmonary window and mediastinal window of malignant lesions
      were significantly less than those of benign ones (P<0.05). The cut-off value on
      pulmonary window was the window width and window level of 1,300 and -220 HU, the
      area under the ROC was 0.830 [sensitivity was 72.5%, specificity was 84.3%; 95%
      confidence interval (CI), 0.712-0.945]. The cut-off value on mediastinal window
      was the window width and window level of 360 and 30 HU, and the area under the
      ROC was 0.623 (was 62.0%, specificity was 55.7%; 95% CI, 0.541-0.745). In
      conclusion, the window technique has high sensitivity and accuracy in qualitative
      diagnosis of the GGO.

PMID- 27895752
TI  - Expression of GOLPH3 protein in colon cancer tissues and its association with the
      prognosis of patients.
AB  - The present study aimed to investigate the expression of Golgi phosphoprotein-3
      (GOLPH3) protein in colon cancer tissues and the association with the prognosis
      of patients. In total, 98 patients with colon cancer admitted to The First
      Affiliated Hospital of Henan University of Science and Technology for surgery
      between June 2011 and June 2013 were taken as the observation group. In addition,
      15 healthy individuals, determined by enteroscopy, were taken as the control
      group. The expressions of GOLPH3 mRNA and protein were detected by reverse
      transcription-polymerase chain reaction and immunohistochemistry, respectively.
      The patients were divided into GOLPH3-positive and GOLPH3-negative groups
      according to the expression of GOLPH3. The expression of GOLPH3 in colon cancer
      and its association with the prognosis of patients was analyzed. The expression
      of GOLPH3 mRNA and protein in colon cancer tissues was significantly increased
      compared with normal colon mucosa (P<0.05); among the tissues, GOLPH3 was not
      expressed in 29 patients and positively expressed in 69 patients. The expression
      of GOLPH3 was negatively associated with the tumor differentiation degree, and
      positively associated with tumor invasion depth, lymph node metastasis and
      clinical stages in GOLPH3-positive patients. The cumulative recurrence rates at
      1, 2 and 3 years were significantly lower in GOLPH3-negative patients (P<0.05).
      The survival rates at 1, 2 and 3 years in the GOLPH3-positive group were
      significantly higher than that of the GOLPH3-negative patients (P<0.05). In
      conclusion, the positive expression of GOLPH3 mRNA and protein in colon cancer
      tissue was significantly increased compared with the control group. GOLPH3
      expression was closely associated with the pathological features, consisting of
      tissue typing, clinical stage, degree of tumor invasion and lymph node
      metastasis, and GOLPH3 expression. Patients with GOLPH3 overexpression also had a
      poor prognosis.

PMID- 27895753
TI  - Drug resistance analysis of gefitinib-targeted therapy in non-small cell lung
      cancer.
AB  - The aim of the study was to examine the drug resistance analysis of gefitinib
      targeted therapy in non-small cell lung cancer (NSCLC). In total, 156 NSCLC
      patients without surgical treatment were selected, including 117 cases of
      adenocarcinoma (75%), to receive single gefitinib 0.25 g/day or combined with
      platinum chemotherapy. Computed tomography was used to evaluate tumor growth for
      the response and non-response groups. The chemotherapy regimen was changed or
      combined with radiotherapy in the non-response group. Tumor progression or
      metastasis in the response group was considered as the generation of drug
      resistance. The chemotherapy regimen was altered in the response group. Eleven
      cases had tumor response in the non-response group after the chemotherapy regimen
      was adjusted (20%), 33 cases had complete response (CR) (32.7%), 44 cases had
      partial response (PR) (43.6%), and 24 cases had stable disease (SD) (23.8%) in
      the response group. The drug resistance rates of CR, PR, and SD showed no
      significant difference (P>0.05). However, the drug-resistant time of CR was
      significantly delayed and the difference was statistically significant (P<0.05).
      The response rates of CR, PR, and SD patients regaining the response rate showed
      no statistical significance after the chemotherapy regimen was adjusted, and the
      difference was not statistically significant (P>0.05). In conclusion, gefitinib
      targeted therapy in NSCLC showed certain drug resistance, which may not be
      related to the response.

PMID- 27895754
TI  - Evaluation of the efficacy of paclitaxel with curcumin combination in ovarian
      cancer cells.
AB  - The aim of the present study was to evaluate the efficacy of paclitaxel combined
      with curcumin (CUR) against drug resistance in ovarian cancer cells. PLGA
      phospholipid-PEG nanoparticles were prepared using the nano precipitation method.
      The size and morphology of the nanoparticles were determined using a transmission
      electron microscope and particle size analyzer. The encapsulation efficiency of
      nanoparticles was determined using the ultrafiltration centrifugation method. The
      dialysis method was used to study the release of PLGA-phospholipid-PEG
      nanoparticles. ADM was used to induce the A2780 cell line (human ovarian cancer
      cell line) to establish the model of the multidrug-resistant (MDR) cell line, and
      the protein activity of P-glycoprotein (P-gp) in the A2780 cell line and
      A2780/ADM resistant cell line was determined using western blot analysis. The
      results showed that, the prepared nanoparticles were uniform in size, with a size
      of approximately 100 nm, and round in shape. Additionally, the nanoparticles had
      a more gentle and slow release than the free drug release. The results of the
      protein trace printing experiment showed that the P-gp content of the drug
      resistant cell line was significantly reduced by the CUR nanoparticles. In
      conclusion, PLGA-phospholipid nanoparticles containing taxol and CUR have
      improved solubility and stability together with a slow release effect. In
      addition, CUR was able to overcome the MDR of tumor cells by elevating the
      paclitaxel concentration in the tumor cells to improve the antitumor activity of
      this combination.

PMID- 27895755
TI  - Inhibitory effects of Chinese nutritional herbs in isogenic breast carcinoma
      cells with modulated estrogen receptor function.
AB  - In estrogen receptor (ER)+ MCF-7 cells, ER represents a ligand-activated
      transcription factor, and 17beta-estradiol (E2) represents its physiological
      ligand. Maintenance of the human breast carcinoma-derived MCF-7 cells with 0.7%
      serum selected a proliferative sub-population of E2-responsive cells with
      transiently non-functional ER due to limited availability of E2. Culture of MCF-7
      cells in the presence of either 0.7% serum, <1 nM E2 or 0.7% serum + 20 nM E2
      selected isogenic cells with either non-functional ER (ER-NF) or functional ER
      (ER-F) phenotype. The two phenotypes responded to the growth-promoting effects of
      E2 and to the growth-inhibitory effects of the selective ER modulator tamoxifen,
      indicating retention of E2 responsiveness. Comparative dose-response experiments
      with Chinese nutritional herbs on ER-NF and ER-F cells identified the inhibitory
      concentration (IC)50 values for these herbs, while the IC50 ratios for the ER
      NF:ER-F phenotypes facilitated their rank ordering in terms of efficacy. Out of
      the 11 efficacious herbs tested, five herbs exhibited ER-F > ER-NF inhibitory
      activity, four exhibited ER-F = ER-NF inhibitory activity and two exhibited ER-NF
      > ER-F inhibitory activity. Extracts from representative herbs, Lycium barbarum
      bark, Epimedium grandiflorum and Cornus officinalis, from each of the three
      groups inhibited anchorage-independent growth, induced G1 or G2/M arrest and/or
      apoptosis, and generated anti-proliferative E2 metabolites. The differential
      growth inhibition in ER-NF and ER-F phenotypes, together with the mechanistic
      efficacy of representative herbs, identified potential leads for their efficacy
      on ER+ and/or ER- breast cancer.

PMID- 27895756
TI  - Role of microRNA-4458 in patients with non-small-cell lung cancer.
AB  - Incidence and progression of non-small-cell lung cancer (NSCLC) is a multi
      factor, multi-step process. The present study investigated the association
      between the expression level of microRNA (miR)-4458 in NSCLC and paracarcinoma
      liver tissues and survival rates, and studied the biological functions of miR
      4458 at the cellular and protein level. NSCLC and paracarcinoma tissues were
      sequenced using a miR expression chip. The association between miR-4458
      expression and tumor-node-metastasis staging, total survival rate and relapse
      free survival rate was analyzed. miR-4458 was subjected to target gene
      prediction. The target protein of cyclin D1 (CCND1) was verified with western
      blot analysis, immunohistochemistry and a luciferase reporter assay. The relative
      level of miR-4458 in paracarcinoma tissues of 9 NSCLC patients decreased from
      2.38 to 0.65 (P<0.001). Total five-year survival rates of the high-expression miR
      4458 group (29.21%) significantly exceeded that of the low-expression group
      (14.37%) (P=0.025). The viability of human lung carcinoma A549 and H460 cells
      transfected with miR-4458 decreased significantly compared with cells transfected
      with a normal control (blank control plasmid) within 72 h (P<0.001). The
      percentage of A549 and H460 cells transfected with a miR-4458 mimic at the cell
      cycle stage G0/G1 was 69.94+/-8.05 and 68.15+/-7.75%, respectively. The
      percentages increased significantly compared with the control group (46.06+/-6.93
      for A549 cells; 45.22+/-7.24 for H640 cells; P<0.001). CCND1 mRNA was
      downregulated significantly in H460 cells 72 h subsequent to the addition of miR
      4458 mimics (P<0.001). The activity of mutant-CCND1 altered slightly, while the
      fluorescence intensity of the wild-type-CCND1 group decreased significantly
      following the addition of miR-4458 mimics. In conclusion, miR-4458 was expressed
      at low levels in lung cancer tissues, and it arrested cells in vitro at stage
      G0/G1 and inhibited cell proliferation. Therefore, miR-4458 may participate in
      the onset of lung cancer as a suppressor gene by inhibiting CCND1.

PMID- 27895757
TI  - Expression of semaphorin 6D and its receptor plexin-A1 in gastric cancer and
      their association with tumor angiogenesis.
AB  - The semaphorin and plexin family of ligands and receptor proteins provides
      important axon growth and guidance cues required for development. In recent
      years, studies have expanded their role in the regulation of cardiac
      morphogenesis and tumorigenesis. However, the mechanism responsible for their
      role in regulating cancer development and progression has not been clarified. In
      the present study, semaphorin 6D (Sema6D) and its receptor plexin-A1 were
      identified to be expressed at high levels in vascular epithelial cells within
      gastric cancer, and were positively correlated with vascular endothelial growth
      factor receptor 2 (VEGFR2). These findings verify our hypothesis that Sema6D and
      plexin-A1 may be closely associated with tumor angiogenesis. Combined with
      experimental observations in the MGC803 gastric cancer cell line, it was observed
      that knocking down plexin-A1 signaling led to a decreased expression of VEGFR2 at
      the messenger RNA and protein levels. Sema6D recognized and activated plexin-A1,
      which subsequently activated its downstream target, VEGFR2. The activation of
      VEGFR2 functioned as a positive regulator of tumor angiogenesis. Our data
      provided an understanding of the complex signaling cascades involved in the
      angiogenesis-related pathway in tumor cells. In light of our observations,
      pharmacological interventions targeting Sema6D/plexin-A1/VEGFR2 signaling may
      potentially be used as a target for the development of novel anti-angiogenic
      drugs in gastric cancer.

PMID- 27895758
TI  - Metaplastic carcinoma of the breast: Imaging and pathological features.
AB  - Metaplastic carcinoma of the breast is a rare form of breast cancer. The aim of
      the present study was to investigate the imaging and pathological features of
      metaplastic carcinoma. The features identified on mammography and sonography were
      retrospectively reviewed in 13 women with metaplastic carcinoma of the breast.
      The results from the mammographs and sonographs were additionally evaluated using
      immunohistochemical staining for the expression of the estrogen receptor (ER) and
      progesterone receptor (PR), receptor tyrosine-protein kinase erbB-2 (CerbB-2) and
      P53. The most common features observed in the mammographs were as follows:
      Irregular and oval shaped masses, 53.8 and 46.2%, respectively; spiculated and
      circumscribed margins, each 30.8%; and high and marginally high density masses,
      69.2 and 30.8%, respectively. The most common sonography features observed were
      as follows: Hypoechoic masses, 84.6%; complex echogenicity, 76.9%; irregular,
      round and oval shaped masses, 69.2, 30.8 and 30.8%, respectively; indistinct and
      circumscribed margins, 53.8 and 46.2%, respectively; an abundant blood flow,
      53.8%; and posterior acoustic enhancement, 61.5%. The immunohistochemical (IHC)
      profile for 13 patients demonstrated that ER was not expressed in 100% of
      patients, PR and CerbB-2 were not present in 92.3% of patients, and P53 was
      present in 63.6% of patients. Therefore, metaplastic carcinoma of the breast
      exhibits more benign IHC features compared with invasive ductal carcinoma. In
      addition, it may be challenging to diagnose patients that do not possess
      posterior acoustic enhancement or express hormone receptors from other types of
      breast cancer.

PMID- 27895759
TI  - Globose, cystic olfactory ensheathing cell tumor: A case report and literature
      review.
AB  - Olfactory ensheathing cell tumor (OECT) is one of the most rare intracranial,
      extra-axial tumors located in the anterior cranial fossa. The present study
      reports a case of a 34-year-old female patient who presented with a history of
      hyposmia for 1 year, as well as a gradual dizziness and emotional lability for 2
      months. Magnetic resonance imaging of the brain revealed a globose, well-defined
      cystic mass at the midline of the anterior cranial fossa, which was confirmed as
      an OECT by histology and was completely resected by bifrontal craniotomy.
      According to the immunostaining results, the tumor was positive for vimentin and
      S100 protein, and negative for epithelial membrane antigen, glial fibrillary
      acidic protein and cluster of differentiation 57 (also known as Leu-7). The
      presentation, imaging findings, histopathological examination and histogenesis of
      OECT are discussed in the present study, along with a literature review.

PMID- 27895760
TI  - Prioritization of non-coding disease-causing variants and long non-coding RNAs in
      liver cancer.
AB  - There are multiple bioinformatics tools available for the detection of coding
      driver mutations in cancers. However, the prioritization of pathogenic non-coding
      variants remains a challenging and demanding task. The present study was
      performed to discriminate non-coding disease-causing mutations and prioritize
      potential cancer-implicated long non-coding RNAs (lncRNAs) in liver cancer using
      a logistic regression model. A logistic regression model was constructed by
      combining 19,153 disease-associated ClinVar and human gene mutation database
      pathogenic variants as the response variable and non-coding features as the
      predictor variable. Genome-wide association study (GWAS) disease or trait
      associated variants and recurrent somatic mutations were used to validate the
      model. Non-coding gene features with the highest fractions of load were
      characterized and potential cancer-associated lncRNA candidates were prioritized
      by combining the fraction of high-scoring regions and average score predicted by
      the logistic regression model. H3K9me3 and conserved regions were the most
      negatively and positively informative for the model, respectively. The area under
      the receiver operating characteristic curve of the model was 0.92. The average
      score of GWAS disease-associated variants was significantly increased compared
      with neutral single nucleotide polymorphisms (5.8642 vs. 5.4707; P<0.001), the
      average score of recurrent somatic mutations of liver cancer was significantly
      increased compared with non-recurrent somatic mutations (5.4101 vs. 5.2768;
      P=0.0125). The present study found regions in lncRNAs and introns/untranslated
      regions of protein coding genes where mutations are most likely to be damaging.
      In total, 847 lncRNAs were filtered out from the background. Characterization of
      this subset of lncRNAs showed that these lncRNAs are more conservative, less
      mutated and more highly expressed compared with other control lncRNAs. In
      addition, 23 of these lncRNAs were differentially expressed between 12 pairs of
      liver cancer and adjacent normal specimens. The logistic regression model is a
      useful tool to prioritize non-coding pathogenic variants and lncRNAs, and paves
      the way for the detection of non-coding driver lncRNAs in liver cancer.

PMID- 27895761
TI  - C5a receptor expression is associated with poor prognosis in urothelial cell
      carcinoma patients treated with radical cystectomy or nephroureterectomy.
AB  - Patients with aggressive urothelial cell carcinoma (UCC) that undergo radical
      cystectomy or nephroureterectomy exhibit markedly high rates of disease
      recurrence and mortality. To select appropriate adjuvant thxerapies in addition
      to radical surgery, the identification of predictive prognostic markers for UCC
      patients is required. The aim of the present study was to identify such markers,
      by evaluating the association of UCC complement component 5 (C5) fragment a
      (C5a)receptor (C5aR) expression, detected using immunohistochemistry, with
      clinicopathological parameters and survival outcomes of UCC patients. The results
      revealed that C5aR was expressed in cancer cells, particularly at the invasive
      front, but not in noncancerous urothelial cells or adjacent cells. The UCC C5aR
      positive rate of patients treated with radical surgeries was 73% (38/52) and the
      rate was 83% (20/24) at stages I-II of disease. No correlation between C5aR
      expression and any of clinicopathological parameters, which included gender,
      tumor location, World Health Organization grade, T stage, vessel invasion and
      stage of disease, was identified. However, univariate and multivariate analyses
      revealed that C5aR-positive UCC patients exhibited significantly lower overall
      survival rates [hazard ratio (HR), 3.14; 95% confidence interval (CI), 1.03-9.60;
      P=0.035 and HR, 3.92; 95% CI, 1.15-13.4; P=0.029, respectively] and 5-year
      survival rates (0.42 vs. 0.83) compared with C5aR-negative UCC patients.
      Furthermore, 5-year survival and disease-specific survival rates were lower in
      patients with C5aR-positive UCC (0.51; 95% CI, 0.30-0.71) than patients with C5aR
      negative UCC (0.83; 95% CI, 0.62-1.00). These results indicate that UCC C5aR
      expression is predictive of poor patient outcomes and thus may lead to the
      appropriate selection of adjuvant therapies at earlier UCC stages, which could
      improve patient prognosis.

PMID- 27895762
TI  - Primary renal lymphoma: A case report and literature review.
AB  - Primary renal lymphoma (PRL) is a rare disease, with no more than 70 cases
      reported in the literature. The present study reports the case of a 70-year-old
      woman with PRL. The patient was asymptomatic, however, a mass on the right kidney
      was identified incidentally during routine physical examination. Computed
      tomography revealed a mass in the right kidney that was 3.6 cm in diameter.
      Subsequently, right nephrectomy was performed. The histological evaluation of the
      nephrectomy specimen showed diffuse large B-cell non-Hodgkin's lymphoma. The
      patient was treated with 6-8 cycles of a cyclophosphamide, epirubicin, vindesine
      and dexamethasone regimen. Follow-up examination performed after 2 months of
      treatment revealed no evidence of local recurrence. The present study also
      reviewed 49 cases of PRL that have been reported since 1989. It was found that a
      shorter survival time was experienced by patients with bilateral PRL (mean, 21
      months) compared with unilateral PRL (mean, 68 months). A shorter survival time
      was also experienced by patients who were treated with chemotherapy only (mean,
      15.8 months) compared with those who were treated with combination chemotherapy
      and surgery (mean, 49.4 months).

PMID- 27895764
TI  - Mitofusin-2 prevents skeletal muscle wasting in cancer cachexia.
AB  - Cancer cachexia remains a leading cause of morbidity and mortality worldwide,
      despite extensive research and clinical trials. The prominent clinical feature of
      cancer cachexia is the continuous loss of skeletal muscle that cannot be fully
      reversed by conventional nutritional support, and that leads to progressive
      functional impairment. The mechanism underlying muscle loss in patients with
      cachexia is poorly understood. The present study analyzed 21 cancer patients with
      or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated
      in the rectus abdominis of patients with cachexia, which was associated with body
      weight loss. In vitro cell experiments indicated that loss of Mfn2 was associated
      with atrophy of the C2C12 mouse myoblast cell line. Furthermore, in vivo animal
      experiments demonstrated that cachexia decreased gastrocnemius muscle mass and
      Mfn2 expression, and overexpression of Mfn2 in gastrocnemius muscle was able to
      partially attenuate cachexia-induced gastrocnemius muscle loss. The results of
      the present study suggested that Mfn2 is involved in cachexia-induced muscle loss
      and may serve as a potential target for therapy of cachexia.

PMID- 27895763
TI  - Small cell lung cancer transformation and the T790M mutation: A case report of
      two acquired mechanisms of TKI resistance detected in a tumor rebiopsy and plasma
      sample of EGFR-mutant lung adenocarcinoma.
AB  - The present study describes the case of a 45-year-old man diagnosed with
      metastatic lung adenocarcinoma, which harbored a deletion within exon 19 of the
      epidermal growth factor receptor (EGFR) gene. The patient was subsequently
      treated with gefitinib (250 mg/day orally from May 2013 to March 2014), but
      developed acquired resistance to the drug following 11 months of treatment. Tumor
      burden molecular analysis was performed on a tumor rebiopsy and plasma sample,
      and histological analysis was also performed on the tumor rebiopsy. A small cell
      transformation retaining the original EGFR mutation was detected in the tumor
      rebiopsy, while the T790M mutation together with the activating ex19del mutation
      were identified only in the plasma sample. The patient was treated with cytotoxic
      chemotherapy (off-label schedule with epirubicin 80 mg/mq and paclitaxel 160
      mg/mq every 21 days for 6 cycles) and radiation (50.4 Gy administered in 28
      fractions of 1.8 Gy once daily for 5.5 weeks) specific for small cell lung
      cancer, and may also have benefitted from treatment with a third generation T790M
      specific EGFR-TKI. To better describe the mechanisms of resistance to TKI
      inhibitors and to optimize therapeutic regimens, the simultaneous analysis of
      tumor biopsies and circulating tumor DNA should be considered.

PMID- 27895766
TI  - Primary mesenchymal tumors of the pancreas in a single center over 15 years.
AB  - In total, 95% of primary tumors in the pancreas are epithelial tumors; primary
      mesenchymal tumors at this site are extremely rare. At present, only one
      comprehensive study about these rare tumors has been performed. Another
      retrospective analysis of these rare tumors is performed in the present study,
      which, to the best of our knowledge, is the first to be performed in China. In
      the present study, 10 patients that underwent resection for primary mesenchymal
      tumors of the pancreas were identified in a 15-year period at the Chinese Academy
      of Medical Sciences and Peking Union Medical College, which accounted for 0.51%
      of the total surgically resected primary tumors of the pancreas at this hospital.
      Among the 10 patients, 7 patients (70%) were diagnosed with benign/borderline
      tumors, and the remaining 3 patients (30%) were diagnosed with malignant tumors.
      It was a unique finding of the present study that the preoperative diagnosis was
      frequently a misdiagnosis, in terms of the specific pathological diagnosis.
      Therefore, although primary mesenchymal tumors of the pancreas are extremely
      rare, they should be considered in order to make the correct preoperative
      diagnosis. Contrarily to a previous study, in the present study, the most common
      benign tumor was not desmoid tumor, but solitary fibrous tumors; the most
      frequent primary sarcoma was not undifferentiated/unclassified sarcoma either. In
      conclusion, the present study aids the understanding of these rare tumors;
      however, primary mesenchymal tumors of the pancreas require additional
      exploration in the future.

PMID- 27895765
TI  - Decreased expression of the CHD5 gene and its clinicopathological significance in
      breast cancer: Correlation with aberrant DNA methylation.
AB  - Chromodomain helicase DNA binding protein 5 (CHD5) has been identified as a tumor
      suppressor in mouse models. Downregulation of CHD5 gene expression is frequently
      observed in breast cancer cells and tissues. This may be explained by deletions
      or other mutations; however, alternative mechanisms require investigation.
      Therefore, the present study evaluated whether CHD5 aberrant methylation has a
      role in primary breast tumors. A total of 389 patients with primary breast cancer
      (including 252 paraffin-embedded specimens and 137 fresh-frozen samples) were
      enrolled in the present study. In the current study, reverse transcription
      polymerase chain reaction (RT-PCR) and nested-methylation-specific PCR were used
      to analyze the mRNA expression and promoter methylation of CHD5 genes in a large
      cohort of breast cancer patients, and to investigate their associations with the
      clinicopathological features of tumors. CHD5 expression was significantly
      suppressed in breast cancer tissues compared with normal breast tissues when
      analyzed by RT-PCR. Furthermore, DNA methylation of CHD5 was more prevalent in
      breast tumors than in normal tissues. CHD5 mRNA levels correlated with the degree
      of CHD5 methylation in breast cancer tissues. Clinicopathological correlation
      analysis revealed that CHD5 promoter methylation was associated with estrogen
      receptor and progesterone receptor status. Thus, downregulation of CHD5, mediated
      by abnormal methylation, may contribute to the development and progression of
      breast cancer.

PMID- 27895767
TI  - A promoter polymorphism in the hMLH1 gene (-93G/A) associated with sporadic
      colorectal cancer.
AB  - Colorectal cancer (CRC) is a worldwide problem for public health. mutL homolog 1
      (MLH1) is a key component of the mismatch repair system, and the MLH1-93G/A
      polymorphism (rs1800734) is predicted to affect MLH1 protein expression,
      suggesting that the polymorphism may be associated with the cancer risk; however,
      the results concerning this have been inconsistent. In order to investigate the
      possible correlation between human (h)MLH1-93G/A polymorphism and the development
      and progression of sporadic CRC (SCRC) in China, the genotypes of hMLH1-93G/A
      were detected by the TaqMan MGB probe method in 312 SCRC patients and 300 healthy
      controls, and immunohistochemical staining was also performed to measure the
      expression of hMLH1 in cases with different alleles among the SCRC patients and
      normal controls. It was observed that the A/A genotype and A allele significantly
      increased the risk of developing Duke's stage C+D CRC and lymphatic metastasis.
      hMLH1 expression of the A allele was lower than that of the G allele in CRC. By
      contrast, there was no statistically significant difference in hMLH1 expression
      for the A allele and the G allele in the normal controls. These results suggested
      that hMLH1-93G/A polymorphism may not be associated with the overall risk of CRC,
      but that the hMLH1-93A/A genotype and A allele are associated with the
      progression of CRC.

PMID- 27895769
TI  - Unusual lower back pain with monocytosis: A case report.
AB  - There are numerous causes of lower back pain. In the oncological setting, spine
      metastasis from a solid tumor is the most common. However, hematological
      disorders should also be taken into consideration. The current study presents a
      case of chronic myelomonocytic leukemia with the initial presentation of chronic
      lower back pain, followed by symptoms that included urinary retention, stool
      incontinence and left gum swelling, in a patient who was eventually diagnosed
      with granulocytic sarcoma (GS) over the sacral region. GS is a rare presentation
      of a tumor consisting of extramedullary leukemic infiltrations, which develop at
      different sites and cause different symptoms. Prompt and correct diagnosis of
      this type of disease may be crucial to improve the survival outcome by the early
      initiation of adequate treatment.

PMID- 27895768
TI  - Role of miR-196 and its target gene HoxB8 in the development and proliferation of
      human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4
      on their expression.
AB  - The present study aimed to investigate the interaction between miR-196 and its
      target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the
      sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin
      (FOLFOX4) chemotherapy (1,200 mg/m2 fluorouracil, 200 mg/m2 leucovorin and 85
      mg/m2 oxaliplatin). In total, 80 tissue samples were collected in the present
      study. In total, 50 patients undergoing preoperative chemotherapy completed at
      least 3 cycles (2 weeks per cycle) of 85 mg/m2 oxaliplatin (day 1) combined with
      a 2 h injection of 200 mg/m2 leucovorin (days 1 and 2), a bolus injection of 400
      mg/m2 and 44 h continuous intravenous infusion of 1,200 mg/m2 fluorouracil.
      Complete response and partial response were included in the chemotherapy
      sensitive group (25 patients), and stable disease and progressive disease were
      included in the chemotherapy resistant group (25 patients). In addition, 30
      patients without preoperative chemotherapy were examined for mRNA and protein
      expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR
      196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In
      addition, the expression of the mRNA and protein of miR-196 and HoxB8 was
      measured in 50 tissue samples obtained from patients that had received FOLFOX4
      neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC
      tissues were significantly increased compared with the corresponding normal
      mucosa tissue (P<0.05). The miR-196 mRNA was significantly correlated with lymph
      node metastasis, tumor stage and distant metastasis (P<0.05). miR-196 was
      indicated to be negatively correlated with HoxB8 mRNA expression (r=-0.458;
      P<0.05). The relative amount of miR-196 in the chemotherapy-sensitive group of
      patients was 0.949+/-0.691, which was increased compared with the chemotherapy
      resistant group (0.345+/-0.536; P<0.01). The relative level of HoxB8 mRNA in the
      chemotherapy-sensitive group was 0.490+/-0.372, which was decreaesd compared with
      the chemotherapy-resistant group (0.725+/-0.438; P<0.05). HoxB8 protein
      expression level in the chemotherapy-sensitive group was decreased compared with
      the chemotherapy-resistant group (Z=-2.396; P=0.017). Overall, miR-196 was
      correlated with metastasis and prognosis, and HoxB8 was highly expressed in CRC
      tissues. The difference in the gene expression of miR-196 and HoxB8 may be
      associated with the sensitivity to FOLFOX4 for CRC patients. In addition, the
      highly expressed miR-196 increased the sensitivity of CRC cells to chemotherapy
      with FOLFOX4 by inhibiting HoxB8.

PMID- 27895770
TI  - Classical intracranial chondrosarcoma: A case report.
AB  - Intracranial chondrosarcoma is a rare malignant cartilage-forming tumor, with
      only a small number of cases in the posterior cranial fossa reported previously.
      The present study reports the case of a 40-year-old male patient who was admitted
      to Tianjin Huanhu Hospital with a progressive headache and dizziness that had
      lasted for 2 years. Physical and neurological examinations were normal.
      Radiography of the skull identified an opaque lesion in the left frontal region
      of the brain. Cranial computed tomography and magnetic resonance imaging revealed
      a lesion with calcification and homogenous contrast enhancement in the left
      frontal region. Subsequently, the patient underwent bicoronal craniotomy and
      gross total resection of the tumor. Pathological examination confirmed the
      diagnosis of classical intracranial chondrosarcoma. The patient was discharged 10
      days after surgery, with no neurological deficit. One month after initial
      discharge, the patient underwent gamma-knife treatment. A follow-up examination 9
      months after surgery revealed that the patient was still alive and had returned
      to work, with no obvious symptoms or evidence of recurrence.

PMID- 27895771
TI  - Co-culture of hepatoma cells with hepatocytic precursor (stem-like) cells
      inhibits tumor cell growth and invasion by downregulating Akt/NF-kappaB
      expression.
AB  - Hepatocytic stem cells (HSCs) have inhibitory effects on hepatocarcinoma cells.
      The present study investigated the effects of HSC activity in hepatocarcinoma
      cells in vitro. A Transwell co-culture system of hepatocytic precursor (stem
      like) WB-F344 cells and hepatoma CBRH-7919 cells was used to assess HSC activity
      in metastasized hepatoma cells in vitro. Nude mouse xenografts were used to
      assess HSC activity in vivo. Co-culture of hepatoma CBRH-7919 cells with WB-F344
      cells suppressed the growth and colony formation, tumor cell migration and
      invasion capacity of CBRH-7919 cells. The nude mouse xenograft assay demonstrated
      that the xenograft size of CBRH-7919 cells following co-culture with WB-F344
      cells was significantly smaller compared with that of control cells. Furthermore,
      the expression levels of the epithelial markers E-cadherin and beta-catenin were
      downregulated, while the mesenchymal markers alpha-SMA and vimentin were
      upregulated. Co-culture of CBRH-7919 cells with WB-F344 cells downregulated NF
      kappaB and phospho-Akt expression. In conclusion, hepatocytic precursor (stem
      like) WB-F344 cells inhibited the growth, colony formation and invasion capacity
      of metastasized hepatoma CBRH-7919 cells in vitro and in vivo by downregulating
      Akt/NF-kappaB signaling.

PMID- 27895773
TI  - Dysregulation of long non-coding RNA profiles in human colorectal cancer and its
      association with overall survival.
AB  - Long non-coding RNAs (lncRNAs) emerged as key regulators of diverse roles during
      colorectal cancer (CRC) carcinogenesis, but their specific function still remains
      to be explored. The present study aimed to re-annotate the Affymetrix Human Exon
      1.0 ST Array for defining differential lncRNAs in CRC. Their prognostic relevance
      was also developed for screening key regulators in CRC. The CRC datasets E-GEOD
      31737, E-MATB-829, Affymetrix colon cancer dataset and E-GEOD-24550 were re
      purposed for searching differential lncRNAs and exploring their association with
      overall survival (OS). The identified lncRNAs were validated in CRC tissues or
      cell lines. As a result, 462, 286 and 166 differential lncRNAs were identified,
      respectively, in three predictive datasets. Among them, 48 lncRNAs were commonly
      observed to exhibit differential expression in the three datasets. Notably, the
      overexpression of family with sequence similarity 83 member H (FAM83H)-antisense
      (AS) 1 (P=0.038) and VPS9 domain containing 1 (VPS9D1)-AS1 (P=0.020) indicated
      shorter OS time than lower expression. The overexpression of FAM83H-AS1 (P=0.033)
      and VPS9D1-AS1 (P=0.011) was validated in cancerous tissues. Thus, FAM83H-AS1 and
      VPS9D1-AS1 may potentially enhance carcinogenesis or may be developed as
      prognostic biomarkers for CRC. In conclusion, a total of 48 CRC-related lncRNAs
      were identified, the majority of which were confirmed to exhibit dysregulation.
      FAM83H-AS1 and VPS9D1-AS1 could have a potential use as prognostic biomarkers for
      CRC patients.

PMID- 27895772
TI  - HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated
      by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma.
AB  - Evidence is rapidly accumulating that long non-coding RNAs (lncRNAs) are involved
      in human tumorigenesis and are dysregulated in multiple cancers, including
      hepatocellular carcinoma (HCC). lncRNAs can regulate essential pathways that
      contribute to tumor initiation and progression with tissue specificity, which
      suggests that lncRNAs may be valuable biomarkers and therapeutic targets. HOX
      transcript antisense intergenic RNA (HOTAIR) has previously been demonstrated to
      be an oncogene and a negative prognostic factor in a variety of cancers; however,
      the factors that contribute to the upregulation of HOTAIR and the interaction
      between HOTAIR and microRNAs (miRNAs or miRs) are largely unknown. In the present
      study, the expression levels of HOTAIR, forkhead box C1 (FOXC1) and miRNA-1 were
      examined in 50 matched pairs of HCC and HCC cells. The effects of HOTAIR on HCC
      cell proliferation were tested using trypan blue exclusion assay. The effect of
      HOTAIR on HCC growth in vivo was determined in a (nu/nu) mouse model. A
      computational screening of HOTAIR promoter was conducted to search for
      transcription factor-binding sites. FOXC1 binding to the promoter region of
      HOTAIR was confirmed using a chromatin immunoprecipitation assay. A search for
      miRNAs that had complementary base paring with HOTAIR was performed utilizing an
      online software program. The interaction between miR-1 and HOTAIR was examined
      using a luciferase reporter assay. Gain and loss of function approaches were used
      to determine the changes of HOTAIR or miR-1 expression. The relative levels of
      FOXC1 and HOTAIR expression in HCC tissues and HepG2 cells were significantly
      higher than those in normal liver LO2 cells and adjacent carcinoma tissues; the
      relative expression of miR-1 exhibited the opposite pattern. Overexpression of
      HOTAIR promoted HCC cell proliferation and progression of tumor xenografts. The
      present authors have demonstrated that FOXC1 binds to the upstream region of
      HOTAIR in HCC cells and that FOXC1 activates lncRNA HOTAIR expression in HCC
      HepG2 cells, which suggests that HOTAIR harbors a miRNA-1 binding site. The
      present data revealed that this binding site is vital for the regulation of miRNA
      1 by HOTAIR. Furthermore, HOTAIR negatively regulated the expression of miRNA-1
      in HepG2 cells. Additionally, the present study demonstrated that the oncogenic
      activity of HOTAIR is in part based on the negative regulation of miR-1. Taken
      together, these results suggest that HOTAIR is a FOXC1-activated driver of
      malignancy, which acts in part through the repression of miR-1.

PMID- 27895774
TI  - A case of distal extrahepatic cholangiocarcinoma with two positive resection
      margins.
AB  - Cholangiocarcinoma is an uncommon primary malignancy of the biliary tract that is
      challenging to diagnose and treat effectively due to its relatively silent and
      late clinical presentation. The present study reports a case of a 60-year-old
      male with distal extrahepatic cholangiocarcinoma with a 3-week history of
      painless obstructive jaundice symptoms and subjective weight loss. Imaging
      revealed an obstructing lesion in the common bile duct, just distal to the
      entrance of the cystic duct. Pathology revealed moderately differentiated
      cholangiocarcinoma with two positive proximal resection margins. The two positive
      resection margins presented a challenge during surgery and points to an urgent
      need for further studies to better illuminate diagnostic and therapeutic options
      for patients with similar clinicopathological presentation.

PMID- 27895775
TI  - High expression of CD39 in gastric cancer reduces patient outcome following
      radical resection.
AB  - Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also known as cluster
      of differentiation (CD)39, is the rate-limiting enzyme in the generation of
      immunosuppressive adenosine and is important in tumor progression. The present
      study evaluated the expression of CD39+ and CD39+ forkhead box P3 (FoxP3)+
      regulatory T (Treg) cells in gastric cancer (GC), and determined their prognostic
      roles in patients with GC following radical resection. It was observed that CD39
      was expressed at significantly higher rates in tumor tissues as compared with
      paired peritumoral tissues. Overexpression of tumor CD39 was correlated with
      overall survival (OS). Furthermore, CD39 expression in GC tissues exhibited a
      prognostic role in OS. The CD39+ FoxP3+/FoxP3+ ratio in tumor tissues was higher
      than that in paired peritumoral tissues, and CD39+ FoxP3+ Treg cells were a
      better prognostic indicator than FoxP3+ Treg cells for OS. Collectively, our
      study indicates that overexpression of CD39 in GC is a predictor of poor outcome
      for GC patients following radical resection. CD39+ FoxP3+ Treg cells are a
      potential target for cancer immunotherapy.

PMID- 27895777
TI  - Cryptotanshinone inhibits lung tumor growth by increasing CD4+ T cell
      cytotoxicity through activation of the JAK2/STAT4 pathway.
AB  - Cryptotanshinone is one of the fat-soluble phenanthrene quinone components. In
      vitro studies have shown that tanshinone compounds can inhibit the proliferation
      of various tumor cells and affect cell cycle distribution. The aim of the present
      study was to better understand the effect of cryptotanshinone on the inhibition
      of small cell lung cancer by cytotoxic cluster of differentiation (CD)4+ T cells
      through activation of the Janus kinase 2/signal transducer and activator of
      transcription 4 (JAK2/STAT4) pathway. The Cell Counting kit-8 assay and the
      lactate dehydrogenase assay were used to analyze the cell proliferation of H446
      and CD4+ T cells, and the cell cytotoxicity of CD4+ and CD8+ T cells,
      respectively. JAK2 and STAT4 protein expression was measured by western blot
      analysis. Cryptotanshinone effectively inhibited the tumor growth of the H446
      cells and the cell proliferation of the CD4+ T cells. Treatment with
      cryptotanshinone increased the cytotoxicity of the CD4+ T cells, but could not
      affect the cytotoxicity of the CD8+ T cells. Meanwhile, cryptotanshinone induced
      phosphorylated (p)-JAK2 and p-STAT4 protein expression in the CD4+ T cells. These
      results suggest that cryptotanshinone inhibits the cell growth of lung tumors by
      increasing CD4+ T cell toxicity through activation of the JAK2/STAT4 pathway.

PMID- 27895776
TI  - Establishment of specific cytotoxic T lymphocyte culture system and its
      inhibitory effect on ovarian cancer.
AB  - The present study aimed to establish a novel method for efficiently inducing
      cytotoxic T lymphocytes (CTLs) in vitro, in order to develop an immune-based
      therapy for suppressing and killing ovarian cancer cells with a high safety and
      efficacy. Peripheral blood mononuclear cells (PBMCs) were stimulated with CpG
      oligodeoxynucleotide (CpGODN) and ginsenoside Rg1, which were united as an immune
      adjuvant, and human epidermal growth factor receptor 2 (HER2/neu) antigen
      peptide, in order to establish a specific CTL culture system in vitro. Chromosome
      karyotype analysis, growth curve construction and flow cytometric analysis of
      immune phenotypes, including cluster of differentiation (CD)3, CD4 and CD8, were
      performed to characterize the stimulated PBMCs in vitro. Subsequently, SKOV3
      ovarian cancer cells were treated with the specific CTL culture system in vitro,
      and MTT assays were performed to test the inhibitory and lethal effects of the
      CTLs on SKOV3 cells. The number of CTLs was significantly increased from day 7 of
      stimulation with the specific mixture (CpGODN, ginsenoside Rg1 and HER2/neu)
      (P<0.01), and plateaued on day 19. Following activation, the number of CD3+,
      CD3+CD4+ and CD3+CD8+ cells was significantly increased (P<0.01). The lymphocyte
      karyotype did not change following exposure to antigen. After treatment with the
      specific CTL system, the number of SKOV3 cells in the experimental group was
      significantly reduced compared with that in the control group (P<0.01). The
      results of the present study suggested that two novel immune adjuvants, CpGODN
      and ginsenoside Rg1, could be combined with the HER2/neu antigen peptide to
      establish a specific CTL culture system in vitro. This system demonstrated a high
      antigen specificity, safety and proliferative ability, and exerted significant
      lethal and inhibitory effects on SKOV3 cells in vitro.

PMID- 27895778
TI  - Regulatory network analysis of genes and microRNAs in human hepatoblastoma.
AB  - Hepatoblastoma (HB) is a common type of primary tumor in children. Previous
      studies have examined the expression of genes, including transcription factors
      (TFs), target genes, host genes and microRNAs (miRNAs or miRs) associated with
      HB. However, the regulatory pathways of miRNAs and genes remain unclear. In the
      present study, a novel perspective is proposed, which focuses on HB and the
      associated regulatory pathways, to construct three networks at various levels,
      including a differentially expressed network, an associated network and a global
      network. Genes and miRNAs are considered as key factors in the network. In the
      three networks, the associations between each pair of factors, including TFs that
      regulate miRNAs, miRNAs that interact with target genes and miRNAs that are
      located at host genes, were analyzed. The differentially expressed network is
      considered to be the most crucial of the three networks. All factors in the
      differentially expressed network were mutated or differentially expressed, which
      indicated that the majority of the factors were cancerogenic factors that may
      lead to HB. In addition, the network contained numerous abnormal linkages that
      may trigger HB. If the expression of each factor was corrected to a normal level,
      HB may be successfully treated. The associated network included more HB
      associated genes and miRNAs, and was useful for analyzing the pathogenesis of HB.
      By analyzing these close associations, the first and the last factor of the
      regulatory pathways were revealed to have important roles in HB. For example, v
      myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN)
      was observed to regulate Homo sapiens (hsa)-miR-221, hsa-miR-18a and hsa-miR-17
      5p, but no miRNAs targeted MYCN. In conclusion, the pathways and mechanisms
      underlying HB were expounded in the present study, which proposed a fundamental
      hypothesis for additional studies.

PMID- 27895779
TI  - Potential impact of mTOR inhibitors on cervical squamous cell carcinoma: A
      systematic review.
AB  - The aim of the present systematic review was to analyze the potential impact of
      mammalian target of rapamycin (mTOR) inhibitors on the treatment of cervical
      squamous cell carcinoma (CSCC). A systematic literature search was conducted in
      PubMed, PMC, Scopus, Cochrane Library, LILACS, Web of Science, Google Scholar and
      ScienceDirect on January 19, 2015, without time and language restrictions.
      Studies that evaluated women of any age with CSCC and who received mTOR
      inhibitors alone or in association with other treatments were considered.
      Randomized and non-randomized clinical trials were included, and the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed.
      Selected studies were methodologically appraised according to the Grades of
      Recommendation, Assessment, Development and Evaluation method to assess the
      quality of evidence. Of 642 identified citations, 43 studies were fully reviewed;
      however, only 3 studies met the inclusion criteria and were used for qualitative
      analysis. Of these, two studies were phase 1 and one was a phase 2 clinical
      trial. The studies included were not conclusive with regard to the association
      between mTOR inhibitor treatment and cervical cancer. The main analysis of
      secondary endpoints revealed that individuals treated with other drugs in
      association with mTOR inhibitors achieved partial responses (15.4-33.3%) or
      stable disease (17.6-28%). Treatment with mTOR inhibitors in general was well
      tolerated in patients with metastatic disease. The predominant toxicities were
      grade 1 and 2. The phase 1 trials included in this review demonstrated that mTOR
      inhibitor treatments are feasible and safe. However, the currently available
      evidence is insufficient to determine the effect of mTOR inhibitors on CSCC, and
      further investigation in high-quality, randomized clinical trials is required.

PMID- 27895780
TI  - Curcumin potentiates the effect of chemotherapy against acute lymphoblastic
      leukemia cells via downregulation of NF-kappaB.
AB  - Acute lymphoblastic leukemia (ALL) accounts for 30% of all pediatric cancers.
      Currently available treatments exhibit toxicity and certain patients may develop
      resistance. Thus, less toxic and chemoresistance-reversal agents are required. In
      the present study, the potential effect of curcumin, a component of Curcuma
      longa, as a pharmacological co-adjuvant of several chemotherapeutic agents
      against ALL, including prednisone, 6-mercaptopurine, dexamethasone,
      cyclophosphamide, l-asparaginase, vincristine, daunorubicin, doxorubicin,
      methotrexate and cytarabine, was investigated in the REH ALL cell line cultures
      treated in combination with chemotherapeutic agents and curcumin. The results of
      cell viability, gene expression and activation of NF-kappaB and caspase 3
      indicated that curcumin potentiates the anticancer effects of the aforementioned
      chemotherapeutic agents in the REH ALL cell line. Following treatment with the
      above chemotherapeutic agents, curcumin enhanced caspase-3 activation and
      downregulated nuclear factor-kappa B (NF-kappaB) activation. Curcumin also
      downregulated the oxidative stress induced by certain chemotherapies. Notably,
      curcumin did not affect the gene expression of cell survival proteins such as B
      cell lymphoma (Bcl)-2, Bcl-extra large, survivin, c-Myc and cyclin D1, which are
      regulated by the NF-kappaB transcription factor. In conclusion, curcumin has the
      potential to improve the effect of chemotherapeutic agents against ALL.

PMID- 27895781
TI  - 9-AAA inhibits growth and induces apoptosis in human melanoma A375 and rat
      prostate adenocarcinoma AT-2 and Mat-LyLu cell lines but does not affect the
      growth and viability of normal fibroblasts.
AB  - The present study found that, similarly to 5-fluorouracil, low concentrations (1
      10 uM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate
      cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line.
      However, at the same concentrations, 9-AAA had no effect on the growth and
      apoptosis of normal human skin fibroblasts (HSFs). The differences between the
      cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in
      malignancy, were found to be relatively small compared with the differences
      between normal HSFs and the cancer cell lines. Visible effects on the cell growth
      and survival of tumor cell lines were observed after 24-48 h of treatment with 9
      AAA, and increased over time. The inhibition of cancer cell growth was found to
      be due to the gradually increasing number of cells dying by apoptosis, which was
      observed using two methods, direct counting and FlowSight analysis.
      Simultaneously, cell motile activity decreased to the same degree in cancer and
      normal cells within the first 8 h of incubation in the presence of 9-AAA. The
      results presented in the current study suggest that short-lasting tests for
      potential anticancer substances can be insufficient; which may result in cell
      type-dependent differences in the responses of cells to tested compounds that act
      with a delay being overlooked. The observed differences in responses between
      normal human fibroblasts and cancer cells to 9-AAA show the requirement for
      additional studies to be performed simultaneously on differently reacting cancer
      and normal cells, to determine the molecular mechanisms responsible for these
      differences.

PMID- 27895782
TI  - Expression of MMP9, SERPINE1 and miR-134 as prognostic factors in esophageal
      cancer.
AB  - Esophageal cancer (EC) is a malignant tumor with a typically poor prognosis for
      patients. It is well known that certain microRNA (miRNA/miR) genes can regulate
      other genes responsible for carcinogenesis. In the present study, a group of
      these genes (miR-21, miR-134, miR-205 and miR-495) and genes connected with
      cancer-related pathways (MET, MMP9, PDGFA and SERPINE1) were chosen for analysis
      in order to find a potential correlation between their expression and the
      clinicopathological factors of EC. Esophageal tumors and adjacent non-cancerous
      tissue specimens were collected from a total of 63 patients and embedded in
      paraffin. Commercial arrays were used on KYSE-30, KYSE-150 and KYSE-270 EC cell
      lines in order to find genes of different expression profiles compared with those
      acquired from the control Het-1A cell line. Quantitative polymerase chain
      reaction was used on formalin-fixed, paraffin-embedded samples in order to
      analyze the expression of the genes chosen in the earlier step. The results were
      analyzed by the Kruskal-Wallis and Mann-Whitney U tests, Spearman's rank
      correlation coefficient, Kaplan-Meier methods and the long-rank test. Only miR
      495 was not expressed in the analyzed samples. The expression of MMP9 and
      SERPINE1 was significantly coefficient with age range (P=0.011 and P=0.044,
      respectively) according to the Kruskal-Wallis test. The Spearman's rank-order
      correlation measurement showed that there was a coefficient correlation between
      age and miR-134 expression. The same measurement demonstrated a correlation
      between age range and MMP9 expression. The expression of miR-134 and MMP9 were
      also found to be correlated. In all cases, a value of P<0.049 was recorded.
      Overall, the present study demonstrated that MMP9, SERPINE1 and miR-134 were the
      most prognostic genes in Caucasian patients with EC.

PMID- 27895783
TI  - Curcumin suppresses colon cancer cell invasion via AMPK-induced inhibition of NF
      kappaB, uPA activator and MMP9.
AB  - Curcumin, an active nontoxic ingredient of turmeric, possesses potent anti
      inflammatory, antioxidant and anti-cancer properties; however, the molecular
      mechanisms of curcumin are not fully understood. The transcription factor nuclear
      factor-kappaB (NF-kappaB) is key in cellular processes, and the
      expression/activation of urokinase-type plasminogen activator (uPA) and matrix
      metalloproteinase-9 (MMP9) are crucial for cell invasion. The present study
      investigated the hypothesis that curcumin inhibits colon cancer cell invasion by
      modulating NF-kappaB-mediated expression and activation of uPA and MMP9. Human
      colon cancer SW480 and LoVo cells were treated with various concentrations of
      curcumin. Curcumin was demonstrated to dose-dependently inhibit the adhesion and
      proliferation ability of LoVo and SW480 cells using Transwell and MTT assays,
      respectively. In addition, curcumin activated 5' AMP-activated protein kinase
      (AMPK) and suppressed p65 NF-kappaB phosphorylation, as shown by western blot
      analysis. Compound C, a potent AMPK inhibitor, abolished curcumin-induced
      inhibition of NF-kappaB, uPA and MMP9, suggesting that AMPK activation is
      responsible for curcumin-mediated NF-kappaB, uPA and MMP9 inhibition. The binding
      activity of NF-kappaB to DNA was examined and western blotting and quantitative
      polymerase reaction was performed to detect the effect of curcumin on the
      expression of uPA and MMP9. The present results revealed that curcumin
      significantly decreased the expression of uPA and MMP9 and NF-kappaB DNA binding
      activity. Furthermore, curcumin decreased the level of the p65 subunit of NF
      kappaB binding to the promoter of the gene encoding uPA and MMP9, which
      suppressed transcriptional activation of uPA and MMP9. Overall, the present data
      suggest that curcumin inhibits colon cancer cell invasion via AMPK activation and
      subsequent inhibition of p65 NF-kappaB, uPA and MMP9. The therapeutic potential
      of curcumin for colon cancer metastasis required additional study.

PMID- 27895785
TI  - Expression and clinicopathological significance of the lncRNA HOXA11-AS in
      colorectal cancer.
AB  - HOXA11 antisense RNA (HOXA11-AS) is a long non-coding RNA (lncRNA) that is
      important in determining cancer progression. HOXA11-AS was recently identified as
      a novel biomarker in lung cancer progression. However, its role in colorectal
      cancer (CRC) remains poorly understood. The present study aimed to analyze lncRNA
      HOXA11-AS expression in CRC and investigate a possible association between HOXA11
      AS and clinicopathological factors. HOXA11-AS expression was examined by reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) in 84 CRC tissues
      and adjacent non-cancerous tissues, in addition to 3 CRC cell lines and 1 human
      normal colorectal cell line. The results demonstrated that HOXA11-AS expression
      was decreased in the CRC tissues and cell lines compared with that of the
      controls (P<0.05). Clinicopathological analysis indicated that low HOXA11-AS
      expression was significantly correlated with tumor size, advanced tumor-node
      metastasis stage, lymph node metastasis and carcinoembryonic antigen level of
      patients with CRC (P<0.05). Furthermore, the areas under the curve (AUC) were
      0.613 and 0.628 for HOXA11-AS, indicating that the lncRNA is able to distinguish
      CRC tissue from non-cancerous tissue, and CRC tissue with lymph node metastasis
      from CRC without lymph node metastasis. Therefore, HOXA11-AS may function as a
      potential biomarker and target for novel therapeutic strategies to treat CRC.

PMID- 27895784
TI  - Resveratrol reverses P-glycoprotein-mediated multidrug resistance of U2OS/ADR
      cells by suppressing the activation of the NF-kappaB and p38 MAPK signaling
      pathways.
AB  - The present study aimed to investigate the reversal effect of resveratrol on the
      phenomenon of multidrug resistance in U2OS/adriamycin (ADR) cells and to clarify
      the molecular mechanisms. To examine the cell survival and half-inhibitory
      concentration (IC50) of ADR in U2OS and U2OS/ADR cells, 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay was used. The accumulation of ADR in
      U2OS and U2OS/ADR cells was investigated by flow cytometry. Reverse transcription
      quantitative polymerase chain reaction and western blot analysis were used to
      detect the expression of multidrug resistance protein 1 (MDR1), P-glycoprotein (P
      gp), p65 and p38. Compared with U2OS cells, the IC50 value of ADR was
      significantly increased in U2OS/ADR cells, which exhibited high levels of MDR1/P
      gp. However, resveratrol could drastically reduce the IC50 value of ADR and the
      expression of MDR1/P-gp, and increased the accumulation of ADR in U2OS/ADR cells.
      In addition, the expression levels of p38 (phosphorylated) and p65 (acetylated
      and total) in U2OS/ADR cells were also significantly suppressed by resveratrol.
      These results suggested that the nuclear factor (NF)-kappaB and p38 mitogen
      activated protein kinase (MAPK) signaling pathways are correlated with ADR
      induced drug resistance in U2OS/ADR cells. Furthermore, resveratrol could
      downregulate the expression of MDR1/P-gp and reverse the drug resistance
      phenomenon in U2OS/ADR cells partly at least by suppressing the activation of the
      NF-kappaB and p38 MAPK signaling pathways.

PMID- 27895786
TI  - Sprouty4 mRNA variants and protein expressions in breast and lung-derived cells.
AB  - Sprouty proteins are modulators of mitogen-induced signalling processes and are
      therefore hypothesized to affect malignant diseases. As a member of the Sprouty
      family, Sprouty4 has been previously shown to function as a tumour suppressor in
      lung and breast cancer. The present study analysed the expression of two known
      Sprouty4 splice variants in cells established from malignant and normal lung and
      breast tissues using semi-quantitative reverse transcription-polymerase chain
      reaction and immunoblotting. The results indicated that the expression of the two
      messenger RNA (mRNA) variants was reduced in the cells derived from malignant
      tissue in comparison to the normal counterparts. Although the expression of the
      two splice variants were associated in both tissue types, on average, the
      relative expression of the longer variant was slightly increased in malignant
      cells compared with normal tissues. Notably, the protein levels reflected the
      expression observed at the mRNA level only in breast-derived cells. Contrarily,
      with regards to the measured mRNA levels, Sprouty4 protein was disproportional
      augmented in lung cells known to harbour the mutated K-Ras gene.

PMID- 27895787
TI  - Runx2 expression: A mesenchymal stem marker for cancer.
AB  - The transcription factor runt-related transcription factor 2 (Runx2) is a master
      gene implicated in the osteogenic differentiation of mesenchymal stem cells, and
      thus serves a determinant function in bone remodelling and skeletal integrity.
      Various signalling pathways regulate Runx2 abundance, which requires a number of
      molecules to finely modulate its expression. Furthermore, this gene may be
      ectopically-expressed in cancer cells. Recent studies have reported the
      involvement of Runx2 in cell proliferation, epithelial-mesenchymal transition,
      apoptosis and metastatic processes, suggesting it may represent a useful
      therapeutic target in cancer treatment. However, studies evaluating this gene as
      a cancer marker are lacking. In the present study, Runx2 expression was analysed
      in 11 different cancer cell lines not derived from bone tumour. In addition, the
      presence of Runx2-related cell-free RNA was examined in the peripheral blood of
      41 patients affected by different forms of tumours. The results demonstrated high
      expression levels of Runx2 in the cancer cell lines and identified the presence
      of Runx2-related cell-free RNA in the peripheral blood of patients with cancer.
      As compared with normal individuals, the expression level was increased by 14.2
      fold in patients with bone metastases and by 4.01-fold in patients without
      metastases. The results of the present study therefore opens up the possibility
      to exploit Runx2 expression as a cancer biomarker allowing the use of minimally
      invasive approaches for diagnosis and follow-up.

PMID- 27895788
TI  - Effects of microRNA-21 on the biological functions of T-cell acute lymphoblastic
      lymphoma/leukemia.
AB  - Previous studies have demonstrated that microRNA-21 (miR-21) is an oncogene and
      is significantly upregulated in tumor tissue. However, its association with T
      cell acute lymphoblastic lymphoma/leukemia (T-ALL) remains poorly understood. The
      aim of the present study was to investigate the effects of miR-21 on T-ALL cells
      by constructing Jurkat cells infected with recombinant adenovirus adv-miR-21 or
      adv-anti-miR-21. In addition, the target gene of miR-21 was identified by reverse
      transcription-quantitative polymerase chain reaction and western blotting. The
      results demonstrated that miR-21 expression in Jurkat cells was markedly
      upregulated. Furthermore, upregulating miR-21 expression in Jurkat cells promoted
      cell proliferation and invasion and decreased the apoptosis rate. By contrast,
      knockdown of miR-21 in Jurkat cells suppressed proliferation and invasion and
      increased the apoptosis rate. Furthermore, the results indicated that signal
      transducer and activator of transcription (STAT) 3 was targeted by miR-21, and
      that miR-21 inhibited STAT3 expression at the protein level rather than at the
      messenger RNA level. In conclusion, targeting the inhibition of miR-21 may be a
      novel therapeutic strategy for patients with T-ALL.

PMID- 27895789
TI  - MicroRNA-181b is downregulated in non-small cell lung cancer and inhibits cell
      motility by directly targeting HMGB1.
AB  - The expression of microRNA-181b (miR-181b) has been investigated in various human
      cancers. However, the expression and functions of miR-181b in non-small cell lung
      cancer (NSCLC) are yet to be studied. In the present study, miR-181b expression
      in NSCLC tissues and cell lines was analyzed by quantitative polymerase chain
      reaction, and was shown to be recurrently downregulated. Following transfection
      of the H23 and H522 NSCLC cells lines with miR-181b, cell migration and cell
      invasion assays were performed to evaluate the effect of miR-181b overexpression
      on the cell motility. It was demonstrated that overexpression of miR-181b
      inhibited the migration and invasion of NSCLC cells. Subsequently, bioinformatics
      analysis, western blotting and luciferase reporter assays were conducted to
      investigate the mechanism underlying the miR-181b-mediated inhibition of NSCLC
      cell motility. It was found that miR-181b directly targeted high-mobility group
      box-1 (HMGB1) in NSCLC cells. These results reveal a novel therapeutic target,
      the miR-181b/HMGB1 axis, in NSCLC. Treatment approaches targeting this axis will
      be beneficial to prevent NSCLC from becoming invasive.

PMID- 27895791
TI  - Nedaplatin enhanced apoptotic effects of ABT-737 in human cancer cells via Mcl-1
      inhibition.
AB  - Platinum compounds, such as cisplatin, carboplatin, oxaliplatin and nedaplatin,
      are widely used to treat a number of solid malignancies. Nedaplatin is a second
      generation platinum complex, based on its pronounced anti-cancer activities
      against several solid tumors being equivalent to that of cisplatin, but with
      lower nephrotoxicity. In this context, the present study aimed to investigate the
      potential anti-cancer effect by combining nedaplatin with ABT-737. It was found
      that nedaplatin greatly increased ABT-737-mediated apoptosis in A549 and 95-D
      cells, accompanied by enhanced cleavage of poly(ADP-ribose) polymerase and
      caspase-3. In addition, this enhancement was also paralleled by cytochrome c
      release and dissipation of mitochondrial membrane potential. Additional
      mechanistic investigations revealed that nedaplatin plus ABT-737 exerted a
      synergistic effect on cancer cells through their ability to accelerate the
      degradation of Mcl-1. The present study has revealed nedaplatin as a pertinent
      sensitizer to ABT-737, which opens up new avenues for this promising BH3-mimetic
      molecule in the clinic.

PMID- 27895790
TI  - Corosolic acid inhibits the proliferation of osteosarcoma cells by inducing
      apoptosis.
AB  - Corosolic acid (CRA), a pentacyclic triterpene isolated from medicinal herbs, has
      been reported to exhibit anticancer properties in several cancers. However, the
      anticancer activity of CRA in osteosarcoma cells is still unclear. In the present
      study, the inhibitory effect of CRA in osteosarcoma MG-63 cells was investigated,
      and the results revealed that CRA significantly inhibited the viability of MG-63
      cells in a dose- and time-dependent manner. A typical apoptotic hallmark such as
      DNA ladder was detected by agarose gel electrophoresis following treatment with
      CRA. Further experiments demonstrated that CRA induced apoptosis of MG-63 cells
      by flow cytometry using propidium iodide and annexin V staining. In addition, it
      was observed that the apoptosis of MG-63 cells induced by CRA was closely
      associated with activation of caspase-3 and caspase-9, loss of mitochondrial
      membrane potential, and release of cytochrome c from mitochondria, suggesting
      that CRA may trigger the activation of the mitochondria-mediated apoptosis
      pathway. In addition, the inhibition of caspase activity attenuated the CRA
      induced apoptosis of MG-63 cells, which further confirmed the role of the
      mitochondrial pathway in CRA-induced apoptosis. These results indicated that CRA
      could induce the apoptosis of osteosarcoma cells through activating the
      mitochondrial pathway, which provides an evidence that CRA may be a useful
      chemotherapeutic agent for osteosarcoma.

PMID- 27895792
TI  - MicroRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of
      autophagy in osteosarcoma cells.
AB  - Osteosarcoma (OS) is the most common cancer of the bone. Chemotherapy is commonly
      used for the clinical treatment of OS. However, chemoresistance to cisplatin
      [also known as diamminedichloridoplatinum (II) (DDP)] is a major obstacle for OS
      therapy, the underlying mechanism of which is not fully understood. The present
      study aimed to investigate the role of microRNA (miR)-199a-5p in the regulation
      of chemoresistance to DDP in OS cells. Reverse transcription-quantitative
      polymerase chain reaction demonstrated that the expression level of miR-199a-5p
      was significantly reduced in human OS MG63 cells. In addition, DDP treatment also
      upregulated the protein levels of light chain 3 (LC3)-II and Beclin1 as well as
      the ratio of LC3-II vs. LC3-I in MG63 cells, indicating that autophagy was
      activated. Restoration of miR-199a-5p expression promoted DDP-induced inhibition
      of MG63 cell proliferation and inhibited DDP-induced autophagy, as indicated by
      the reduced protein levels of LC3-II and Beclin1 and the ratio of LC3-II vs. LC3
      I. Finally, luciferase reporter assay data revealed that miR-199a-5p directly
      targeted Beclin1 and negatively mediated Beclin1 expression at a post
      transcriptional level in MG63 cells. In conclusion, our study suggests that miR
      199a-5p promotes the cytotoxicity of DDP in OS cells via inhibition of autophagy.
      Therefore, miR-199a-5p/autophagy signaling is involved in chemoresistance and may
      become a potential target for the treatment of DDP-resistant OS.

PMID- 27895793
TI  - Evaluation of recurrent disease in the re-staging of colorectal cancer by 18F-FDG
      PET/CT: Use of CEA and CA 19-9 in patient selection.
AB  - The aim of the present retrospective study was to evaluate the sensitivity and
      specificity of fluorodeoxyglucose (18F-FDG) positron emission tomography/computed
      tomography (PET/CT) in assessing the recurrence of colorectal cancer (CRC) with
      regard to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9).
      18F-FDG PET/CT was performed in 100 patients for the re-staging of CRC. Therapy
      was discontinued prior to the examination. The mean (+/- standard deviation) CEA
      value (measured ~30 days prior to PET/CT examination) was 23.71 (+/-107) ng/ml,
      whereas the CA 19-9 value was 72 (+/-190.3) U/ml. Differences in CEA and CA 19-9
      values in patients with scans that were positive or negative for recurrence were
      analyzed by means of a receiver operating characteristic (ROC) curve. ROC curves
      were used for the calculation of the sensitivity and specificity of 18F-FDG
      PET/CT for the CEA and CA 19-9 levels. The results of the 18F-FDG PET/CT were
      found to be associated with the CEA level (P=0.001), but not with the CA 19-9
      level (P=0.43). PET/CT was positive for recurrence in 60 patients (60.0%), whose
      mean CEA and CA 19-9 values were 33.07+/-136.7 ng/ml and 75.24+/-192.3 U/ml,
      respectively. PET/CT was negative for recurrence in 40 patients (40.0%), whose
      mean CEA and CA 19-9 values were 10.15+/-30 ng/ml and 67.76+/-190 U/ml,
      respectively. On the basis of ROC curve analysis, the best compromise between
      sensitivity and specificity was achieved for CEA levels of 3.5 ng/ml
      [sensitivity, 80%; 95% confidence interval (CI), 67-89%; and specificity, 60%;
      95% CI, 45-78%]. The study concluded that the detection of recurrence by 18F-FDG
      PET/CT in patients treated for CRC is associated with CEA, but not CA 19-9 serum
      levels. Moreover, 18F-FDG PET/CT should be recommended in patients with suspected
      CRC recurrence even when they present with CEA levels below the normal cut-off.

PMID- 27895794
TI  - Trousseau's syndrome caused by bladder cancer producing granulocyte colony
      stimulating factor and parathyroid hormone-related protein: A case report.
AB  - The present study reports a rare case of bladder cancer that caused Trousseau's
      syndrome, a malignancy-associated hypercoagulative state leading to venous or
      arterial thrombosis. A 38-year-old Japanese female patient experienced a sudden
      onset of visual field defects and lower limb weakness. Cerebral magnetic
      resonance imaging revealed multi-regional hypointense areas compatible with acute
      cerebral infarction. Despite the repeated administration of anticoagulant
      treatment with heparin, the condition could not be adequately controlled and
      thromboembolic events occasionally recurred. Several tumor markers, including
      carbohydrate antigen 19-9, cancer antigen 125, carcinoembryonic antigen,
      cytokeratin 19 fragment and squamous cell carcinoma antigen levels, were
      elevated. Consequently, computed tomography scans were performed, which revealed
      a massive bladder tumor with multiple bone and lymph node metastases. The patient
      also exhibited other paraneoplastic disorders, including leukocytosis due to
      granulocyte colony-stimulating factor (G-CSF) production, and hypercalcemia due
      to parathyroid hormone-related protein (PTHrP) production. Transurethral
      resection of the bladder tumor was performed, and the tumor was pathologically
      confirmed as urothelial cell carcinoma. Immunohistochemical testing revealed
      positive staining for G-CSF and PTHrP. Despite undergoing gemcitabine/cisplatin
      based systemic chemotherapy, the disease developed rapidly and the patient
      succumbed to the disease within 3 months of initial symptoms. The present case
      indicates that occult visceral malignancy should be considered in patients with
      unexplained thromboembolism.

PMID- 27895795
TI  - Growth differentiating factor-15 (GDF-15): A potential biomarker and therapeutic
      target for cancer-associated weight loss.
AB  - Growth differentiating factor-15 (GDF-15), also known as macrophage inhibiting
      factor-1, is a member of the transforming growth factor-beta superfamily, which
      has been implicated in cancer-associated weight loss. The present study
      investigated the association between cancer-associated weight loss and plasma GDF
      15 concentration, as well as other biomarkers, in patients with metastatic lung
      or exocrine pancreatic cancer. A total of 218 patients were enrolled over a 1
      year period. The patient cohort included 152 patients with incurable lung cancer
      and 66 patients with incurable pancreatic cancer. Of the 218 patients, 98 (45%)
      reported >5% weight loss, 62 (28%) reported <=5% weight loss and 58 (27%)
      reported no weight loss in the 6 months prior to diagnosis. In lung cancer
      patients, higher circulating GDF-15 levels were significantly associated with
      weight loss; lung cancer patients who reported >5% weight loss (n=56) were found
      to exhibit twice the circulating concentration of GDF-15 compared with those that
      exhibited no weight loss (n=48) (P<0.0001). Additional mediators, including
      Activin A, interleukin (IL)-12, vascular endothelial growth factor A, IL-1
      receptor alpha, eotaxin and platelet derived growth factor-BB, were also
      associated with weight loss; however, the associations were not as strong. In
      pancreatic cancer patients, no association between GDF-15 levels and weight loss
      was identified. However, higher circulating GDF-15 levels were consistently
      associated with poor survival in univariate [hazard ratio (HR), 1.13; 95%
      confidence interval (CI), 1.02-1.23; P=0.016] and multivariate [HR, 1.1; 95% CI,
      1.02-1.24; P=0.03] analysis, respectively. Thus, GDF-15 requires further study as
      a biomarker and potential therapeutic target in cancer-associated weight loss,
      particularly in lung cancer patients.

PMID- 27895797
TI  - UGT1A1*6, UGT1A7*3 and UGT1A9*1b polymorphisms are predictive markers for severe
      toxicity in patients with metastatic gastrointestinal cancer treated with
      irinotecan-based regimens.
AB  - Irinotecan-induced severe neutropenia and diarrhea, which remain unpredictable,
      has restrained the dose and clinical efficiency of irinotecan administration. In
      the present study, a total of 70 irinotecan-treated patients with histologically
      confirmed metastatic gastrointestinal cancer were enrolled. Despite genotyping
      well-reported alleles, direct sequencing was specifically adopted to avoid ethnic
      heterogeneity and to identify novel variations. The promoter (-1000 bp) and exon
      1 regions of UDP glucuronosyltransferase family 1 member A complex locus (UGT1A1)
      gene family members UGT1A1, UGT1A7 and UGT1A9 were sequenced, and comprehensive
      analysis of their genetic polymorphisms was performed to determine the
      association between inherited genetic variations and irinotecan-induced toxicity.
      A total of 23 different genetic variants were detected in the present study,
      including 2 novel polymorphisms. The results of the present study revealed that
      UGT1A1*6 and UGT1A7*3 are risk factors for irinotecan-induced severe neutropenia,
      and UGT1A9*1b is associated with severe diarrhea. These results may provide
      biomarkers for the selection of the optimal chemotherapy for Chinese patients
      with metastatic gastrointestinal cancer.

PMID- 27895798
TI  - Exploring the impact of EGFR T790M neighboring SNPs on ARMS-based T790M mutation
      assay.
AB  - The present study aimed to explore the influence of T790M neighboring single
      nucleotide polymorphism (SNP) on the sensitivity of amplification refractory
      mutation system (ARMS)-based T790M mutation assay. Three ARMS-quantitative
      polymerase chain reaction (qPCR) systems (system 1 had a forward ARMS primer
      without rs1050171, system 2 included a forward ARMS primer with rs1050171 and
      system 3 contained the above two forward ARMS primers) were used to detect the
      T790M mutation in two series plasmid samples and genomic DNA (gDNA) of the cell
      line H1975. A total of 670 formalin-fixed paraffin-embedded (FFPE) tumor samples
      from non-small cell lung cancer patients were used to detect the epidermal growth
      factor receptor (EGFR) gene T790M mutation by direct sequencing and ARMS-qPCR.
      The ARMS-qPCR system 1 effectively detected samples with as low as 1% T790M
      mutant plasmid 1 (without rs1050171) and with 50% T790M mutant plasmid 2 (with
      rs1050171), while the ARMS-qPCR system 2 detected samples with 20 and 50% T790M
      mutant plasmid 1, in addition to samples with 1% T790M mutant plasmid 2. For the
      ARMS-qPCR system 3, samples with as low as 1% T790M mutant plasmids 1 or 2 were
      effectively detected. For gDNA analysis of the cell line H1975, the T790M
      mutation was effectively detected by the ARMS-qPCR systems 2 and 3 (~50% mutation
      rate), but was detected with a low mutation abundance by the ARMS-qPCR system 1
      (~1% mutation rate). Of the 670 FFPE samples, 5 cases were identified to have the
      T790M mutation by sequencing and by the ARMS-qPCR system 1. One sample (named
      N067), which was considered as T790M-negative by sequencing, was demonstrated to
      have the T790M mutation using the ARMS-qPCR system 1. Sample N094, which was
      variant homozygous for rs1050171 and was indicated to be T790M-negative by
      sequencing and by the ARMS-qPCR system 1, was identified to have the T790M
      mutation with the ARMS-qPCR system 3. The A-variant allele frequency of rs1050171
      was observed to be 28.2% in the 670 FFPE tumor samples, while the presence of
      rs148188503 (c. C2355T, p. T785T) was observed in sample N558, and a novel SNP
      with a base substitution (c. T2375C) at position 792 (p. L792P) in exon 20 of the
      EGFR gene was observed in sample N310. rs1050171 is a high-frequency SNP located
      near T790M, and the mutation statuses of rs1050171 appear to influence the
      sensitivity of the ARMS-based T790M detection system, thus generating a 14.3%
      false-negative rate (1/7). The present study proposes the risk that target
      neighboring SNPs (as far as 8 bp away in the present study) may exert on the
      sensitivity of ARMS-based detection methods.

PMID- 27895796
TI  - Promotion of metastasis of thyroid cancer cells via NRP-2-mediated induction.
AB  - Tumor-node-metastasis is one of the leading causes of morbidity and mortality in
      thyroid cancer patients. Upregulation of vascular endothelial growth factor-C
      (VEGF-C) increases the migratory ability of thyroid cancer cells to lymph nodes.
      Expression of neuropilin-2 (NRP-2), the co-receptor of VEGF-C, has been reported
      to be correlated with lymph node metastasis in human thyroid cancer. The present
      study investigated the role of VEGF-C/NRP-2 signaling in the regulation of
      metastasis of two different types of human thyroid cancer cells. The results
      indicated that the VEGF-C/NRP-2 axis significantly promoted the metastatic
      activities of papillary thyroid carcinoma cells through the activation of the
      mitogen-activated protein kinase (MAPK) kinase (MEK)/extracellular signal
      regulated kinase and p38 MAPK signaling cascades. However, neither MEK or p38
      MAPK inhibitors produced significant inhibition of the migratory activity and
      invasiveness regulated by the VEGF-C/NRP-2 axis in follicular thyroid carcinoma
      cells. Finally, VEGF-C/NRP-2-mediated invasion and migration of thyroid cancer
      cells required the expression of NRP-2. The present results demonstrate that the
      promotion of metastasis by VEGF-C is mainly due to the upregulation of NRP-2 in
      thyroid cancer cells, and this metastatic activity regulated by the VEGF-C/NRP-2
      axis provides further insight into the process of tumor metastasis.

PMID- 27895799
TI  - Routine blood examinations combined with morphological analysis for the diagnosis
      of myelodysplastic/myeloproliferative neoplasms.
AB  - In 2008, the World Health Organization (WHO) introduced a new hematological
      neoplasm category; myelodysplastic/myeloproliferative neoplasms (MDS/MPN), which
      included four main subcategories. This disease is often misdiagnosed, which
      delays effective therapy. The present study evaluated the role of routine blood
      examinations and morphological analysis of peripheral blood cells in the reliable
      diagnosis of MDS/MPN. In total, 236 adult MDS/MPN patients were analyzed. The
      analysis included 10 routine blood parameters measured using a Sysmex XE-2100TM,
      3 differential percentage parameters and 7 morphological features of peripheral
      blood cells which were analyzed by optical microscopy, and 3 differential
      absolute count numbers obtained based on the corresponding differential
      percentages and absolute count of blood cells. The parameters were compared among
      the subcategories and a value of P<0.05 was considered to indicate a
      statistically significant difference. The median white blood cell and hemoglobin
      counts of the patients were 18.0*109/l and 88 g/l, respectively. The proportion
      of monocytes increased to 8% (1.82*109/l), the proportion of blast cells
      increased to 1% (0.5*109/l) and that of neutrophil precursors increased to 10%
      (1.98*109/l). A total of 87% of all patients presented with hypogranulation and
      71% presented with abnormal condensed nuclear chromatin in granulocytes. Atypical
      monocytes were observed in 73% of all patients and Pseudo-Pelger cells were
      observed in 60%. Significant differences were detected among the subcategories.
      The present study demonstrated that combining blood routine parameters and the
      morphological analysis of peripheral blood cells have an essential role in the
      reliable diagnosis of MDS/MPN based on WHO categories.

PMID- 27895800
TI  - A novel curcumin analogue is a potent chemotherapy candidate for human
      hepatocellular carcinoma.
AB  - Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to
      prevent tumor development in cancer; however, the clinical application of CUR is
      limited by its instability and poor metabolic properties. The present study
      offers an strategy for a novel CUR analogue, (1E,4E)-1,5-bis(2-bromophenyl)penta
      1,4-dien-3-one (GL63), to be used as a potential therapeutic agent for
      hepatocellular carcinoma (HCC) in vitro and in vivo. The current study
      demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC
      cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK
      HEP-1 cells in a dose-dependent manner, and was more potent than CUR, according
      to the flow cytometry data. The present study demonstrated for the first time
      that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator
      of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective
      effect against HCC cell growth. GL63 was more effective than CUR in regulating
      STAT3 downstream targets, which contributed to the suppression of cell
      proliferation and the induction of cell apoptosis. In addition, the effects of
      GL63 were tested in a model of N-nitrosodiethylamine (DEN)-induced HCC in Wistar
      rats. Although macroscopic and microscopic features suggested that both GL63 and
      CUR were effective in inhibiting DEN-induced hepatocarcinogenesis, GL63 exerted a
      stronger effect than CUR. Immunohistochemical analysis for proliferating cell
      nuclear antigen demonstrated significant differences among the DEN-bearing non
      treated, DEN-bearing GL63-treated and DEN-bearing, CUR-treated groups (P=0.039).
      It was concluded that GL63 was a potent agent able to suppress the proliferation
      of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more
      favorable pharmacological activity than CUR, and may be a more potent compound
      for the prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

PMID- 27895801
TI  - In vitro evaluation of a combination treatment involving anticancer agents and an
      aurora kinase B inhibitor.
AB  - Aurora kinase B (AURKB) inhibitors are regarded as potential molecular-targeting
      drugs for cancer therapy. The present study evaluated the cytotoxic effect of a
      combination of AZD1152-hQPA, an AURKB inhibitor, and various anticancer agents on
      the HeLa human cervical cancer cell line, as well as its cisplatin-resistant
      equivalent HCP4 cell line. It was demonstrated that AZD1152-hQPA had an
      antagonistic effect on the cytotoxicity of cisplatin, etoposide and doxorubicin,
      but had a synergistic effect on that of all-trans-retinoic acid (ATRA), Am80 and
      TAC-101, when tested on HeLa cells. Cisplatin, etoposide and doxorubicin were
      shown to increase the cellular expression of AURKB, while ATRA, Am80 and TAC-101
      downregulated its expression. These results suggested that AURKB expression is
      regulated by these anticancer agents at the transcriptional level, and that the
      level of expression of AURKB may influence the cytotoxic effect of AZD1152-hQPA.
      Therefore, when using anticancer agents, decreasing the expression of AURKB using
      a molecular-targeting drug may be an optimal therapeutic strategy.

PMID- 27895802
TI  - Vitamin C induces apoptosis in AGS cells via production of ROS of mitochondria.
AB  - It has been demonstrated that vitamin C exhibits anti-cancer activity in various
      tumor cell lines; however, its specific mechanism of action remains unknown.
      Although the diagnosis and therapy of cancer patients have markedly improved in
      recent years, safer and more cost-effective treatments are still required.
      Therefore, the present study examined the effect of vitamin C on the induction of
      cell death in gastric cancer and its underlying mechanism of action. It was
      observed that the cytotoxicity of vitamin C on the human gastric cancer cell line
      AGS is dependent on the apoptotic pathway, including caspase cascades, but not on
      the necroptotic pathway. It was demonstrated that the vitamin C-induced calcium
      influx and ROS generation have critical roles in the induction of apoptosis.
      Furthermore, vitamin C treatment depleted adenosine triphosphate (ATP) production
      in AGS cells, and the autophagy pathway may be involved in this process. Taken
      together, the current study suggests that a high dose of vitamin C may induce
      gastric cancer cell apoptosis through the dysfunction of mitochondria, including
      calcium influx, reactive oxygen species generation and ATP depletion.

PMID- 27895804
TI  - Erratum to: 18beta-Glycyrrhetinic acid exerts protective effects against
      cyclophosphamide-induced hepatotoxicity: potential role of PPARgamma and Nrf2
      upregulation.
AB  - [This corrects the article DOI: 10.1007/s12263-015-0491-1.].

PMID- 27895803
TI  - Time-course microarray analysis for identifying candidate genes involved in
      obesity-associated pathological changes in the mouse colon.
AB  - BACKGROUND: Obesity is known to increase the risk of colorectal cancer. However,
      mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are
      not completely understood. The purposes of this study were to identify
      differentially expressed genes in the colon of mice with diet-induced obesity and
      to select candidate genes as early markers of obesity-associated abnormal cell
      growth in the colon. METHODS: C57BL/6N mice were fed normal diet (11% fat energy)
      or high-fat diet (40% fat energy) and were euthanized at different time points.
      Genome-wide expression profiles of the colon were determined at 2, 4, 8, and 12
      weeks. Cluster analysis was performed using expression data of genes showing log2
      fold change of >=1 or <=-1 (twofold change), based on time-dependent expression
      patterns, followed by virtual network analysis. RESULTS: High-fat diet-fed mice
      showed significant increase in body weight and total visceral fat weight over 12
      weeks. Time-course microarray analysis showed that 50, 47, 36, and 411 genes were
      differentially expressed at 2, 4, 8, and 12 weeks, respectively. Ten cluster
      profiles representing distinguishable patterns of genes differentially expressed
      over time were determined. Cluster 4, which consisted of genes showing the most
      significant alterations in expression in response to high-fat diet over 12 weeks,
      included Apoa4 (apolipoprotein A-IV), Ppap2b (phosphatidic acid phosphatase type
      2B), Cel (carboxyl ester lipase), and Clps (colipase, pancreatic), which
      interacted strongly with surrounding genes associated with colorectal cancer or
      obesity. CONCLUSIONS: Our data indicate that Apoa4, Ppap2b, Cel, and Clps are
      candidate early marker genes associated with obesity-related pathological changes
      in the colon. Genome-wide analyses performed in the present study provide new
      insights on selecting novel genes that may be associated with the development of
      diseases of the colon.

PMID- 27895805
TI  - Blood-based DNA methylation as biomarker for breast cancer: a systematic review.
AB  - Multiple studies have investigated global DNA methylation profiles and gene
      specific DNA methylation in blood-based DNA to develop powerful screening markers
      for cancer. This systematic review summarizes the current evidence on methylation
      studies that investigated methylation level of blood-derived DNA of breast cancer
      (BC) patients in comparison to healthy controls by conducting a systematic
      literature review in PubMed and Web of Science. Essential results, such as
      methylation levels of BC cases and healthy controls, p values, and odds ratios,
      were extracted from these studies by two investigators independently. Overall, 45
      publications met the inclusion criteria for this review. DNA from whole blood, as
      well as cell-free DNA (cfDNA) from serum or plasma, was used in these studies.
      The most common method used for measuring global DNA methylation was the
      investigation of repetitive elements as surrogates and the application of array
      based genome-wide methylation analysis. For measuring gene-specific methylation
      level, methylation-specific PCR and pyrosequencing were the most frequently used
      methods. Epigenome-wide blood DNA hypomethylation in BC patients were reported in
      several studies; however, the evidence is still not conclusive. The most
      frequently investigated gene in whole blood was BRCA1, which was found more
      frequently methylated in patients compared to controls. RASSF1A was the most
      widely investigated gene in cfDNA of serum or plasma, which was also found more
      frequently methylated in patients compared to controls. Several of the eligible
      studies reported the associations of global hypomethylation and increased BC
      risk. Studies investigated associations between gene-specific methylation and BC
      risk, while got heterogeneous results. But two studies reported that
      hypermethylation of ATM gene was associated with increased BC risk, which suggest
      the potential use of this gene for BC risk stratification. Overall, our review
      suggests the possibility of using blood-based DNA methylation marker as promising
      marker for BC risk stratification, as several studies found associations between
      certain methylation level in blood and BC risk. However, so far, the evidence is
      still quite limited. Optimal markers are yet to be developed and promising
      results needed to be validated in prospective study cohorts and tested in large
      screening populations.

PMID- 27895809
TI  - Localized prostate cancer.

PMID- 27895807
TI  - cPAS-based sequencing on the BGISEQ-500 to explore small non-coding RNAs.
AB  - BACKGROUND: We present the first sequencing data using the combinatorial probe
      anchor synthesis (cPAS)-based BGISEQ-500 sequencer. Applying cPAS, we
      investigated the repertoire of human small non-coding RNAs and compared it to
      other techniques. RESULTS: Starting with repeated measurements of different
      specimens including solid tissues (brain and heart) and blood, we generated a
      median of 30.1 million reads per sample. 24.1 million mapped to the human genome
      and 23.3 million to the miRBase. Among six technical replicates of brain samples,
      we observed a median correlation of 0.98. Comparing BGISEQ-500 to HiSeq, we
      calculated a correlation of 0.75. The comparability to microarrays was similar
      for both BGISEQ-500 and HiSeq with the first one showing a correlation of 0.58
      and the latter one correlation of 0.6. As for a potential bias in the detected
      expression distribution in blood cells, 98.6% of HiSeq reads versus 93.1% of
      BGISEQ-500 reads match to the 10 miRNAs with highest read count. After using
      miRDeep2 and employing stringent selection criteria for predicting new miRNAs, we
      detected 74 high-likely candidates in the cPAS sequencing reads prevalent in
      solid tissues and 36 candidates prevalent in blood. CONCLUSIONS: While there is
      apparently no ideal platform for all challenges of miRNome analyses, cPAS shows
      high technical reproducibility and supplements the hitherto available platforms.

PMID- 27895811
TI  - Radionuclides.

PMID- 27895810
TI  - Chemotherapy research for metastatic prostate cancer.

PMID- 27895812
TI  - Androgen receptor axis-targeted agents.

PMID- 27895808
TI  - Mendelian inheritance of trimodal CpG methylation sites suggests distal cis
      acting genetic effects.
AB  - BACKGROUND: Environmentally influenced phenotypes, such as obesity and insulin
      resistance, can be transmitted over multiple generations. Epigenetic
      modifications, such as methylation of DNA cytosine-guanine (CpG) pairs, may be
      carriers of inherited information. At the population level, the methylation state
      of such "heritable" CpG sites is expected to follow a trimodal distribution, and
      their mode of inheritance should be Mendelian. METHODS: Using the Illumina
      Infinium 450 K DNA methylation array, we determined DNA CpG-methylation in blood
      cells from a family cohort 123 individuals of Arab ethnicity, including 18
      elementary father-mother-child trios, we asked whether Mendelian inheritance of
      CpG methylation is observed, and most importantly, whether it is independent of
      any genetic signals. Using 40* whole genome sequencing, we therefore excluded all
      CpG sites with possibly confounding genetic variants (SNP) within the binding
      regions of the Illumina probes. RESULTS: We identified a total of 955 CpG sites
      that displayed a trimodal distribution and confirmed trimodality in a study of
      1805 unrelated Caucasians. Of 955 CpG sites, 99.9% observed a strict Mendelian
      pattern of inheritance and had no SNP within +/-110 nucleotides of the CpG site
      by design. However, in 97% of these cases a distal cis-acting SNP within a +/-1
      Mbp window was found that explained the observed CpG distribution, excluding the
      hypothesis of epigenetic inheritance for these clear-cut trimodal sites. Using
      power analysis, we showed that in 46% of all cases, the closest CpG-associated
      SNP was located more than 1000 bp from the CpG site. CONCLUSIONS: Our findings
      suggest that CpG methylation is maintained over larger genomic distances.
      Furthermore, nearly half of the SNPs associated with these trimodal sites were
      also associated with the expression of nearby genes (P = 4.08 * 10-6), implying a
      regulatory effect of these trimodal CpG sites.

PMID- 27895806
TI  - Genome-wide epigenomic profiling for biomarker discovery.
AB  - A myriad of diseases is caused or characterized by alteration of epigenetic
      patterns, including changes in DNA methylation, post-translational histone
      modifications, or chromatin structure. These changes of the epigenome represent a
      highly interesting layer of information for disease stratification and for
      personalized medicine. Traditionally, epigenomic profiling required large amounts
      of cells, which are rarely available with clinical samples. Also, the cellular
      heterogeneity complicates analysis when profiling clinical samples for unbiased
      genome-wide biomarker discovery. Recent years saw great progress in
      miniaturization of genome-wide epigenomic profiling, enabling large-scale
      epigenetic biomarker screens for disease diagnosis, prognosis, and stratification
      on patient-derived samples. All main genome-wide profiling technologies have now
      been scaled down and/or are compatible with single-cell readout, including: (i)
      Bisulfite sequencing to determine DNA methylation at base-pair resolution, (ii)
      ChIP-Seq to identify protein binding sites on the genome, (iii) DNaseI-Seq/ATAC
      Seq to profile open chromatin, and (iv) 4C-Seq and HiC-Seq to determine the
      spatial organization of chromosomes. In this review we provide an overview of
      current genome-wide epigenomic profiling technologies and main technological
      advances that allowed miniaturization of these assays down to single-cell level.
      For each of these technologies we evaluate their application for future biomarker
      discovery. We will focus on (i) compatibility of these technologies with methods
      used for clinical sample preservation, including methods used by biobanks that
      store large numbers of patient samples, and (ii) automation of these technologies
      for robust sample preparation and increased throughput.

PMID- 27895813
TI  - Cow's milk allergy: towards an update of DRACMA guidelines.
AB  - BACKGROUND: In 2010, the diagnosis and treatment of IgE-mediated CMA were
      systematized in a GRADE guideline. OBJECTIVES & METHODS: After 6 years, the state
      of the knowledge in diagnosis and treatment of CMA has largely evolved. We
      summarize here the main advances, and exemplify indicating some specific points:
      studies aimed at better knowledge of the effects of breastfeeding and the
      production of new special formulae intended for the treatment of CMA. The
      literature (PubMed/MEDLINE) was searched using the following algorithms: (1)
      [milk allergy] AND diagnosis; (2) [milk allergy] AND [formul*] OR [breast*],
      setting the search engine [6-years] time and [human] limits. The authors drew on
      their collective clinical experience to restrict retrieved studies to those of
      relevance to a pediatric allergy practice. RESULTS: Several clinical studies did
      address the possibility to diagnose CMA using new tools in vitro and in vivo, or
      to diagnose it without any evaluation of sensitization. Some studies also
      addressed the clinical role of formulae based on milk hydrolysates, soy, or rice
      hydrolysates in the treatment of CMA. Many studies have elucidated the effects of
      selective nutrients in breastfed infants on their immunologic and neurologic
      characteristics. CONCLUSIONS: Evidence-based diagnostic criteria should be
      identified for non-IgE-mediated CMA. Debate is ongoing about the best substitute
      for infants with CMA. In particular, Hydrolyzed Rice Formulae have been widely
      assessed in the last six years. In the substitute choice, clinicians should be
      aware of recent studies that can modify the interpretation of the current
      recommendations. New systematic reviews and metanalyses are needed to confirm or
      modify the current DRACMA recommendations.

PMID- 27895814
TI  - Robotic rectal surgery: State of the art.
AB  - Laparoscopic rectal surgery has demonstrated its superiority over the open
      approach, however it still has some technical limitations that lead to the
      development of robotic platforms. Nevertheless the literature on this topic is
      rapidly expanding there is still no consensus about benefits of robotic rectal
      cancer surgery over the laparoscopic one. For this reason a review of all the
      literature examining robotic surgery for rectal cancer was performed. Two
      reviewers independently conducted a search of electronic databases (PubMed and
      EMBASE) using the key words "rectum", "rectal", "cancer", "laparoscopy", "robot".
      After the initial screen of 266 articles, 43 papers were selected for review. A
      total of 3013 patients were included in the review. The most commonly performed
      intervention was low anterior resection (1450 patients, 48.1%), followed by
      anterior resections (997 patients, 33%), ultra-low anterior resections (393
      patients, 13%) and abdominoperineal resections (173 patients, 5.7%). Robotic
      rectal surgery seems to offer potential advantages especially in low anterior
      resections with lower conversions rates and better preservation of the autonomic
      function. Quality of mesorectum and status of and circumferential resection
      margins are similar to those obtained with conventional laparoscopy even if
      robotic rectal surgery is undoubtedly associated with longer operative times.
      This review demonstrated that robotic rectal surgery is both safe and feasible
      but there is no evidence of its superiority over laparoscopy in terms of
      postoperative, clinical outcomes and incidence of complications. In conclusion
      robotic rectal surgery seems to overcome some of technical limitations of
      conventional laparoscopic surgery especially for tumors requiring low and ultra
      low anterior resections but this technical improvement seems not to provide,
      until now, any significant clinical advantages to the patients.

PMID- 27895816
TI  - Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic
      cancer.
AB  - A perioperative multimodal strategy including combination chemotherapy and
      radiotherapy, in addition to surgical resection, has been acknowledged to improve
      patient prognosis. However chemotherapy has not been actively applied as an
      immunomodulating modality because of concerns about various immunosuppressive
      effects. It has recently been shown that certain chemotherapeutic agents could
      modify tumor microenvironment and host immune responses through several
      underlying mechanisms such as immunogenic cell death, local T-cell infiltration
      and also the eradication of immune-suppressing regulatory cells such as
      regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better
      understanding of the cell components in the tumor microenvironment and the effect
      of chemotherapy to improve tumor microenvironment, it has been gradually clear
      that the chemotherapeutic agents is two-edged sword to have both immune promoting
      and suppressing effects. The cellular components of the tumor microenvironment
      include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor
      associated macrophages, myeloid derived suppressor cells and cancer associated
      fibroblasts. Based on the better understanding of tumor microenvironment
      following chemotherapy, the treatment protocol could be modified as personalized
      medicine and the prognosis of pancreas cancer would be more improved utilizing
      multimodal chemotherapy. Here we review the recent advances of chemotherapy to
      improve tumor microenvironment of pancreatic cancer, introducing the unique
      feature of tumor microenvironment of pancreatic cancer, interaction between anti
      cancer reagents and these constituting cells and future prospects.

PMID- 27895817
TI  - Current noninvasive tests for colorectal cancer screening: An overview of
      colorectal cancer screening tests.
AB  - Colorectal cancer (CRC) has become the third most common cancer in the world.
      Screening has been shown to be an effective way to identify early CRC and
      precancerous lesions, and to reduce its morbidity and mortality. Several types of
      noninvasive tests have been developed for CRC screening, including the fecal
      occult blood test (FOBT), the fecal immunochemical test (FIT), the fecal-based
      DNA test and the blood-based DNA test (the SEPT9 assay). FIT has replaced FOBT
      and become the major screening test due to high sensitivity, specificity and low
      costs. The fecal DNA test exhibited higher sensitivity than FIT but its current
      cost is high for a screening assay. The SEPT9 assay showed good compliance while
      its performance in screening needs further improvements. These tests exhibited
      distinct sensitivity and specificity in screening for CRC and adenoma. This
      article will focus on the performance of the current noninvasive in vitro
      diagnostic tests that have been used for CRC screening. The merits and drawbacks
      for these screening methods will also be compared regarding the techniques, usage
      and costs. We hope this review can provide suggestions for both the public and
      clinicians in choosing the appropriate method for CRC screening.

PMID- 27895818
TI  - Case of pseudo-Meigs' syndrome caused by gastric cancer-related metastatic
      ovarian tumor with prolonged survival.
AB  - A 48-year-old woman presented with bilateral enlarged ovaries, ascites, bilateral
      pleural effusion, and advanced gastric cancer. Pleural fluid cytology did not
      reveal malignant cells. Oophorectomy, performed as a palliative procedure, was
      followed by rapid resolution of the pleural effusion and ascites. The patient was
      diagnosed with pseudo-Meigs' syndrome, and underwent chemotherapy followed by
      partial gastrectomy. At the last follow-up, 84 mo following oophorectomy, she was
      alive, and free of disease recurrence, despite not receiving any further
      treatment. Pseudo-Meigs' syndrome should be considered in patients with bilateral
      ovarian tumors, ascites and pleural effusion, and treatment such as oophorectomy
      may result in symptomatic improvement and better prognosis in similar patients.

PMID- 27895815
TI  - Molecular predictive markers in tumors of the gastrointestinal tract.
AB  - Gastrointestinal malignancies are among the leading causes of cancer-related
      deaths worldwide. Like all human malignancies they are characterized by
      accumulation of mutations which lead to inactivation of tumor suppressor genes or
      activation of oncogenes. Advances in Molecular Biology techniques have allowed
      for more accurate analysis of tumors' genetic profiling using new breakthrough
      technologies such as next generation sequencing (NGS), leading to the development
      of targeted therapeutical approaches based upon biomarker-selection. During the
      last 10 years tremendous advances in the development of targeted therapies for
      patients with advanced cancer have been made, thus various targeted agents,
      associated with predictive biomarkers, have been developed or are in development
      for the treatment of patients with gastrointestinal cancer patients. This review
      summarizes the advances in the field of molecular biomarkers in tumors of the
      gastrointestinal tract, with focus on the available NGS platforms that enable
      comprehensive tumor molecular profile analysis.

PMID- 27895820
TI  - Sleep, circadian dysrhythmia, obesity and diabetes.
AB  - Synchrony of biological processes with environmental cues developed over
      millennia to match growth, reproduction and senescence. This entails a complex
      interplay of genetic, metabolic, chemical, light, hormonal and hedonistic factors
      across life forms. Sleep is one of the most prominent rhythms where such a match
      is established. Over the past 100 years or so, it has been possible to disturb
      the synchrony between sleep-wake cycle and environmental cues. Development of
      electric lights, shift work and continual accessibility of the internet has
      disrupted this match. As a result, many non-communicable diseases such as
      obesity, insulin resistance, type 2 diabetes, coronary artery disease and
      malignancies have been attributed in part to such disruption. In this
      presentation a review is made of the origin and evolution of sleep studies, the
      pathogenic mediators for such asynchrony, clinical evidence and relevance and
      suggested management options to deal with the disturbances.

PMID- 27895822
TI  - Linagliptin alleviates fatty liver disease in diabetic db/db mice.
AB  - AIM: To study the effects of linagliptin on the structural signs of non-alcoholic
      fatty liver disease (NAFLD) in db/db mice. METHODS: Male diabetic db/db mice
      (BKS.Cg-Dock7m+/+Leprdb/J) aged 10 wk received the dipeptidyl peptidase 4 (DPP4)
      inhibitor linagliptin (10 mg/kg) or saline as a placebo once per day by gavage
      for 8 wk. Intact db/db mice served as controls. Structural changes in the liver
      were analyzed from light and electron microscopic images of sections from intact,
      placebo-treated and linagliptin-treated animals. We estimated the changes in
      hepatocytes, sinusoidal cells, liver microvasculature and lymphatic roots.
      Hepatic staining for lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)
      was assessed by immunohistochemistry. RESULTS: In 18-wk-old diabetic mice, liver
      steatosis (predominantly microvesicular and mediovesicular steatosis) was
      accompanied by dilation of the roots of the lymphatic system, interlobular blood
      vessels and bile canaliculi. Compared to saline-treated mice, linagliptin-treated
      mice exhibited a reduction in the mean numeral densities of hepatocytes with
      lipid droplets (92.4% +/- 1.7% vs 64.9% +/- 5.8% per field of view, P = 0.0002)
      and a lower proportion of hepatocytes with a high density of lipid droplets
      (20.7% +/- 3.6% vs 50.4% +/- 3.1%, P = 0.0007). We observed heterogeneous
      hepatocytes and relatively preserved cell structures in the linagliptin group.
      Dilation of blood and lymphatic vessels, as well as ultrastructural changes in
      the hepatocyte endoplasmic reticulum and mitochondria, were alleviated by
      linagliptin treatment. In intact and placebo-treated mice, immunohistochemical
      staining for LYVE-1 was observed in the endothelial cells of interlobular
      lymphatic vessels and on the membranes of some endothelial sinusoidal cells. We
      observed an enlarged LYVE-1 reaction area in linagliptin-treated mice compared to
      intact and placebo-treated mice. The improvement in the structural parameters of
      the liver in linagliptin-treated mice was independent to changes in the plasma
      glucose levels. CONCLUSION: The DPP4 inhibitor linagliptin alleviates liver
      steatosis and structural changes in the hepatic microvasculature and lymphatic
      roots in a model of NAFLD in diabetic db/db mice.

PMID- 27895821
TI  - Implanting 1.1B4 human beta-cell pseudoislets improves glycaemic control in
      diabetic severe combined immune deficient mice.
AB  - AIM: To investigate the potential of implanting pseudoislets formed from human
      insulin-releasing beta-cell lines as an alternative to islet transplantation.
      METHODS: In this study, the anti-diabetic potential of novel human insulin
      releasing 1.1B4 beta-cells was evaluated by implanting the cells, either as free
      cell suspensions, or as three-dimensional pseudoislets, into the subscapular
      region of severe combined immune deficient mice rendered diabetic by single high
      dose administration of streptozotocin. Metabolic parameters including food and
      fluid intake, bodyweight and blood glucose were monitored throughout the study.
      At the end of the study animals were given an intraperitoneal glucose tolerance
      test. Animals were then culled and blood and tissues were collected for analysis.
      Insulin and glucagon contents of plasma and tissues were measured by insulin
      radioimmunoassay and chemiluminescent enzyme-linked immunosorbance assay
      respectively. Histological analyses of pancreatic islets were carried out by
      quantitative fluorescence immunohistochemistry staining. RESULTS: Both
      pseudoislet and cell suspension implants yielded well vascularised beta-cell
      masses of similar insulin content. This was associated with progressive
      amelioration of hyperphagia (P < 0.05), polydipsia (P < 0.05), body weight loss
      (P < 0.05), hypoinsulinaemia (P < 0.05), hyperglycaemia (P < 0.05 - P < 0.001)
      and glucose tolerance (P < 0.01). Islet morphology was also significantly
      improved in both groups of transplanted mice, with increased beta-cell (P < 0.05 
      P < 0.001) and decreased alpha cell (P < 0.05 - P < 0.001) areas. Whereas mice
      receiving 1.1B4 cell suspensions eventually exhibited hypoglycaemic
      complications, pseudoislet recipients displayed a more gradual amelioration of
      diabetes, and achieved stable blood glucose control similar to non-diabetic mice
      at the end of the study. CONCLUSION: Although further work is needed to address
      safety issues, these results provide proof of concept for possible therapeutic
      applicability of human beta-cell line pseudoislets in diabetes.

PMID- 27895823
TI  - Effect of pioglitazone on nerve conduction velocity of the median nerve in the
      carpal tunnel in type 2 diabetes patients.
AB  - AIM: To evaluate the impact of pioglitazone pharmacotherapy in median nerve
      electrophysiology in the carpal tunnel among type 2 diabetes patients. METHODS:
      The study was executed in patients with type 2 diabetes, treated with oral drugs,
      categorized under pioglitazone or non-pioglitazone group (14 in each group), and
      who received electrophysiological evaluation by nerve conduction velocity at
      baseline and 3 mo. RESULTS: At 3 mo, pioglitazone-category had inferior amplitude
      in sensory median nerve [8.5 interquartile range (IQR) = 6.5 to 11.5) vs non
      pioglitazone 14.5 (IQR 10.5 to 18.75)] (P = 0.002). Non-pioglitazone category
      displayed amelioration in amplitude in the sensory median nerve [baseline 13 (IQR
      = 9 to 16.25) vs 3 mo 8.5 (IQR = 6.5 to 11.5)] (P = 0.01) and amplitude in motor
      median nerve [baseline 9 (IQR = 4.75 to 11) vs 3 mo 6.75 (IQR = 4.75 to 10.25)]
      (P = 0.049); and deterioration of terminal latency of in motor ulnar nerve
      [baseline 2.07 (IQR = 1.92 to 2.25) vs 3 mo 2.16 (IQR = 1.97 to 2.325)] (P =
      0.043). There was amelioration of terminal latency in sensory ulnar nerve
      [baseline 2.45 (IQR = 2.315 to 2.88) vs 3 mo 2.37 (IQR = 2.275 to 2.445) for
      pioglitazone group (P = 0.038). CONCLUSION: Treatment with pioglitazone
      accentuates probability of compressive neuropathy. In spite of comparable
      glycemic control over 3 mo, patients treated with pioglitazone showed superior
      electrophysiological parameters for the ulnar nerve. Pioglitazone has favourable
      outcome in nerve electrophysiology which was repealed when the nerve was
      subjected to compressive neuropathy.

PMID- 27895825
TI  - The MMJ: A work in glowing progress.

PMID- 27895819
TI  - Nutrition, insulin resistance and dysfunctional adipose tissue determine the
      different components of metabolic syndrome.
AB  - Obesity is an excessive accumulation of body fat that may be harmful to health.
      Today, obesity is a major public health problem, affecting in greater or lesser
      proportion all demographic groups. Obesity is estimated by body mass index (BMI)
      in a clinical setting, but BMI reports neither body composition nor the location
      of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes
      accounted for approximately 65% of all deaths, and adiposity and mainly abdominal
      adiposity are associated with all these disorders. Adipose tissue could expand to
      inflexibility levels. Then, adiposity is associated with a state of low-grade
      chronic inflammation, with increased tumor necrosis factor-alpha and interleukin
      6 release, which interfere with adipose cell differentiation, and the action
      pattern of adiponectin and leptin until the adipose tissue begins to be
      dysfunctional. In this state the subject presents insulin resistance and
      hyperinsulinemia, probably the first step of a dysfunctional metabolic system.
      Subsequent to central obesity, insulin resistance, hyperglycemia,
      hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are
      grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an
      energy balance is critical to maintain a healthy body weight, mainly limiting the
      intake of high energy density foods (fat). However, high-carbohydrate rich (CHO)
      diets increase postprandial peaks of insulin and glucose. Triglyceride-rich
      lipoproteins are also increased, which interferes with reverse cholesterol
      transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich
      diets could move fat from peripheral to central deposits and reduce adiponectin
      activity in peripheral adipose tissue. All these are improved with
      monounsaturated fatty acid-rich diets. Lastly, increased portions of omega-3 and
      omega-6 fatty acids also decrease triglyceride levels, and complement the healthy
      diet that is recommended in patients with MetS.

PMID- 27895824
TI  - Relationship between depression and diabetes in pregnancy: A systematic review.
AB  - AIM: To systematically review the literature on women with both diabetes in
      pregnancy (DIP) and depression during or after pregnancy. METHODS: In this
      systematic literature review, PubMed/MEDLINE and EMBASE were searched (13
      November 2015) using terms for diabetes (type 1, type 2, or gestational),
      depression, and pregnancy (no language or date restrictions). Publications that
      reported on women who had both DIP (any type) and depression or depressive
      symptoms before, during, or within one year after pregnancy were considered for
      inclusion. All study types were eligible for inclusion; conference abstracts,
      narrative reviews, nonclinical letters, editorials, and commentaries were
      excluded, unless they provided treatment guidance. RESULTS: Of 1189 articles
      identified, 48 articles describing women with both DIP and depression were
      included (sample sizes 36 to > 32 million). Overall study quality was poor; most
      studies were observational, and only 12 studies (mostly retrospective database
      studies) required clinical depression diagnosis. The prevalence of concurrent DIP
      (any type) and depression in general populations of pregnant women ranged from 0%
      to 1.6% (median 0.61%; 12 studies). The prevalence of depression among women with
      gestational diabetes ranged from 4.1% to 80% (median 14.7%; 16 studies). Many
      studies examined whether DIP was a risk factor for depression or depression was a
      risk factor for DIP. However, there was no clear consensus for either
      relationship. Importantly, we found limited guidance on the management of women
      with both DIP and depression. CONCLUSION: Given the increasing prevalence of
      diabetes and depression, high-quality research and specific guidance for
      management of pregnant women with both conditions are warranted.

PMID- 27895826
TI  - Motivation of health surveillance assistants in Malawi: A qualitative study.
AB  - BACKGROUND: Motivation of health workers is a critical component of performance
      and is shaped by multiple factors. This study explored factors that influence
      motivation of health surveillance assistants (HSAs) in Malawi, with the aim of
      identifying interventions that can be applied to enhance motivation and
      performance of HSAs. METHODS: A qualitative study capturing the perspectives of
      purposively selected participants was conducted in two districts: Salima and
      Mchinji. Participants included HSAs, health managers, and various community
      members. Data were collected through focus group discussions (n = 16) and in
      depth interviews (n = 44). The study sample was comprised of 112 women and 65
      men. Qualitative data analysis was informed by existing frameworks on factors
      influencing health worker motivation. RESULTS: Our analysis identified five key
      themes shaping HSA motivation: salary, accommodation, human resource management,
      supplies and logistics, and community links. Each of these played out at
      different levels-individual, family, community, and organisational-with either
      positive or negative effects. Demotivating factors related primarily to the
      organisational level, while motivating factors were more often related to
      individual, family, and community levels. A lack of financial incentives and
      shortages of basic supplies and materials were key factors demotivating HSAs.
      Supervision was generally perceived as unsupportive, uncoordinated, and top-down.
      Most HSAs complained of heavy workload. Many HSAs felt further recognition and
      support from the Ministry of Health, and the development of a clear career
      pathway would improve their motivation. CONCLUSIONS: Factors shaping motivation
      of HSAs are complex and multilayered; experiences at one level will impact other
      levels. Interventions are required to enhance HSA motivation, including
      strengthening the supervision system, developing career progression pathways, and
      ensuring clear and transparent incentives. HSAs have unique experiences, and
      there is need to hear and address these to better enable HSAs to cope with the
      challenging conditions they work in.

PMID- 27895827
TI  - Malawian impressions of expatriate physicians: A qualitative study.
AB  - BACKGROUND: In many low-income countries, including Malawi, expatriate physicians
      serve diverse roles in clinical care, education, mentorship, and research. A
      significant proportion of physicians from high-income countries have global
      health experience. Despite the well-known benefits of global health experiences
      for expatriates, little is known about local physician and trainee impressions of
      their expatriate counterparts. The objective of this study was to explore
      University of Malawi College of Medicine (COM) physicians' and trainees'
      impressions of expatriate physicians. METHODS: We conducted a cross-sectional
      qualitative study using semi-structured interviews with COM medical students,
      interns, registrars, and faculty. Through open coding, we developed a codebook
      that we applied to interview transcripts and used thematic analysis to identify
      major themes. RESULTS: We interviewed 46 participants from across the continuum
      of medical education at two teaching hospitals in Malawi. Participants discussed
      themes within the following domains: perceived benefits of expatriate physicians
      in Malawi, perceived challenges, past contributions, and perceived roles that
      expatriate physicians should play going forward. Malawian faculty and trainees
      appreciated the approachability, perspectives, and contribution to education that
      expatriates have provided, though at times some have been perceived as
      aggressive, unable to relate to patients and trainees, deficient at adapting to
      the setting, and self-serving. Potential roles that Malawian physicians and
      trainees feel expatriates should serve include education, training, capacity
      building, and facilitating exchange opportunities for local physicians and
      trainees. CONCLUSIONS: This study highlights the perceived benefits and
      challenges that physicians and trainees at the COM have experienced with their
      expatriate counterparts, and suggests roles that expatriates should play while
      abroad. These findings can be used to help inform existing global health
      guidelines, assist with the establishment of host institution expectations for
      global health programmes, and guide individual expatriate physicians who hope to
      optimise their roles abroad.

PMID- 27895828
TI  - Quality of facility-based family planning services for adolescents in Malawi:
      Findings from a national census of health facilities.
AB  - BACKGROUND: The main objective of this study was to describe the quality, in
      terms of provision and experience of care, of facility-based family planning
      services for adolescents compared to older clients in Malawi. METHODS: Secondary
      data analysis was performed on data obtained from the Service Provision
      Assessment survey 2013-14, a census of all formal health facilities in the
      country. For the present study the inclusion criterion was that the client's age
      was recorded in the data set, which gave a weighted total of 1388 observations of
      consultations, reflecting provision of care, and client exit interviews,
      reflecting experience of care. RESULTS: The youngest clients (age group 13 to 19
      years) had twice the odds of reporting a better experience of care compared to
      clients aged 26 and older (odds ratio [OR] 2.03, 95% confidence interval [CI]
      1.15 to 3.54, P = 0.013). The standard of observed provision was low, typically
      with half or more of the mandated elements of care omitted. Compared with clients
      aged over 25, provision of care was slightly better for adolescents, with a
      coefficient of 4.56 on a percentage scale (95% CI 0.90 to 8.23, P = 0.015) and a
      coefficient of 2.33 for those aged 20-25 (95% CI 0.21 to 4.44, P = 0.032).
      Clients seen in facilities under nongovernmental management had better provision
      of care compared to government facilities, with a coefficient of 12.35 (95% CI
      6.70 to 18.01, P < 0.001); care was worse for clients seen in clinics compared to
      hospitals (coefficient -6.88, 95% CI -11.41 to -2.35, P = 0.003) and also for
      clients seen by health surveillance assistants compared to those seen by a
      clinician (coefficient -9.41, 95% CI -15.53 to -3.29, P = 0.003). CONCLUSIONS:
      Quality of care for adolescents attending facility-based family planning services
      was slightly better than for older clients, but this is overshadowed by the
      finding of a low standard of care overall. Health system strengthening,
      especially at the clinic level, is a policy and programming priority that will
      contribute to adolescent reproductive health in Malawi.

PMID- 27895830
TI  - Development of a subspecialty cardiology curriculum for paediatric registrars in
      Malawi: Implementation of a long-distance hybrid model.
AB  - BACKGROUND: Malawi has a high burden of paediatric cardiac disease but a limited
      number of health providers familiar with these chronic diseases. Given the rising
      number of Malawian postgraduate paediatric trainees at the University of Malawi
      College of Medicine, we sought to remedy this lack of basic cardiology training
      with a long-distance, module-based curriculum that could be utilised
      independently, as needed, with on-site teaching. We also wished to evaluate the
      initial modules for utility and improvement in knowledge and confidence in each
      topic. METHODS: After an initial site visit to determine curriculum needs, online
      modules with interactive evaluations and quizzes were developed by a paediatric
      cardiologist in the United States, in collaboration with paediatric registrar
      training directors in Malawi. This online interactive curriculum was followed by
      several site visits to Malawi, by the United States-based paediatric
      cardiologist, to provide bedside teaching, case-based discussions and hands-on
      skill training in cardiac ultrasound and electrocardiogram interpretation.
      Evaluation of the curriculum model included post-module quizzes on cardiac topics
      as well as registrar self-assessments regarding confidence in content areas.
      RESULTS: The average post-module quiz score was 93.6%. Repeat testing with the
      same questions four months later yielded an average score of 78%, with a range
      from 60 to 100%. Pre- and post-module registrar self-assessment regarding
      confidence in content areas showed a substantial gain in knowledge and confidence
      mean. In their qualitative feedback, registrars noted that the modules were
      helpful in studying for their certifying examinations, and all four of the
      registrars sitting Part I of their Malawian and South African paediatric
      certifying examinations passed. CONCLUSIONS: Our innovative hybrid approach,
      combining online educational modules with in-person teaching visits, is a useful
      approach in expanding paediatric cardiology subspecialty education in Malawi.

PMID- 27895829
TI  - Correlates of cannabis use among high school students in Shamva District,
      Zimbabwe: A descriptive cross-sectional study.
AB  - BACKGROUND: We set out to determine the predisposing, enabling, and reinforcing
      factors that influence cannabis use in young people aged 13 to 19 years in Shamva
      District, Zimbabwe. METHODS: A descriptive cross-sectional study focusing on the
      correlates of cannabis use was conducted among 311 school-going adolescents who
      were selected using multistage sampling. RESULTS: Eight percent of the students
      in our sample reported current use of cannabis. Associations were found between
      cannabis use and alcohol consumption (P < 0.001), cigarette smoking (P < 0.001),
      and having had engaged in sexual intercourse (P < 0.001). Significant
      relationships were found between recreational use of cannabis and having family
      members, friends, and parents who have used cannabis (P < 0.001). CONCLUSIONS:
      Students who reported using alcohol, smoking cigarettes, and having had engaged
      in sexual activity were more likely to use cannabis. There is need for
      identification of these risky behaviours among students, and ecological
      frameworks and holistic approaches in health promotion programming should be
      fostered in an effort to increase awareness of the potential harmful effects of
      cannabis use on adolescents' health and life outcomes.

PMID- 27895831
TI  - The spectrum of heart disease in adults in Malawi: A review of the literature
      with reference to the importance of echocardiography as a diagnostic modality.

PMID- 27895833
TI  - Climate change as the biggest threat to public health in southern Africa and
      measures to reduce its impacts.

PMID- 27895832
TI  - Clostridium difficile: A healthcare-associated infection of unknown significance
      in adults in sub-Saharan Africa.
AB  - BACKGROUND: Clostridium difficile infection (CDI) causes a high burden of disease
      in high-resource healthcare systems, with significant morbidity, mortality, and
      financial implications. CDI is a healthcare-associated infection for which the
      primary risk factor is antibiotic usage, and it is the leading cause of bacterial
      diarrhoea in HIV-infected patients in the United States. Little is known about
      the disease burden of CDI in sub-Saharan Africa, where HIV and healthcare
      associated infections are more prevalent and antibiotic usage is less restricted.
      This article reviews published literature on CDI in sub-Saharan Africa,
      highlighting areas for future research. METHODS: English language publications
      since 1995 were identified from online databases (PubMed, Medline, Google
      Scholar, and SCOPUS), using combinations of keywords "C. difficile", "Africa",
      and "HIV". RESULTS: Ten relevant studies were identified. There was considerable
      variation in the methodologies used to assess for carriage of toxigenic C.
      difficile and its associations. Eight studies reported carriage of toxigenic C.
      difficile. Three (of three) studies found an association with antibiotic usage.
      One (of four) studies showed an association with HIV infection. One study showed
      no association with degree of immunosuppression in HIV. Two (of three) studies
      showed an association between carriage of toxigenic C. difficile and diarrhoeal
      illness. CONCLUSIONS: While the carriage of toxigenic C. difficile is well
      described in sub-Saharan Africa, the impact of CDI in the region remains poorly
      understood and warrants further research.

PMID- 27895834
TI  - Profile Interview: Dr Lucinda Manda-Taylor: "A good leader should be passionate
      because leadership is not simply about having a position".

PMID- 27895837
TI  - Communicating science beyond the MMJ.

PMID- 27895836
TI  - Reflections on research at the College of Medicine: Excellence yesterday, today,
      tomorrow.

PMID- 27895835
TI  - Reflections on the first twenty-five years of the University of Malawi College of
      Medicine.
AB  - September 2016 marks 25 years since the College of Medicine of the University of
      Malawi was established. In this article we reflect on its conception, birth,
      adolescence, and youth. The contributions of multiple stakeholders are celebrated
      while being mindful of the ongoing efforts to consolidate past and current gains.
      For instance, the College of Medicine was, until recently, the only medical
      school in the country, but a new private medical school has just been opened in
      Lilongwe. International partnerships and wide-ranging resource mobilisation from
      both internal and international funders has been the hallmark of the growth and
      expansion of the Malawi College of Medicine. Further, the expanding needs for
      specialists in several clinical and non-clinical areas among the health
      professions calls for responsive strategies to address this and other human
      resources needs.

PMID- 27895839
TI  - Letter from ... Malawi: the first year of the College of Medicine of the
      University of Malawi.

PMID- 27895838
TI  - A medical career in Malawi - personal reflections.

PMID- 27895840
TI  - The Malawi "hybrid" medical graduates (1992-1998).
AB  - In April 1991, the Malawi College of Medicine opened its doors to Malawi medical
      students who had undertaken all but the final year of their undergraduate
      training in the United Kingdom. The first batch qualified with the MB BS degrees
      of the University of Malawi in September 1992. Since then and up to July 1998,
      112 doctors have been produced. They are all Malawians, 90 males and 22 females,
      29%, 31% and 40% respectively come from the Northern, Central and Southern
      regions of Malawi. Seventy-one per cent of the graduates had passed through
      Chancellor College, Zomba, and 27% had attended the Kamuzu Academy, Kasunga,
      Malawi. So far, most of these graduates have remained in Malawi, working in
      various locations in government and mission hospitals and at the University of
      Malawi. Many have shown encouraging interest in pursuing postgraduate education.
      In September 1994 the epoch of hybridisation was brought to a close with the
      admission of the first set of students who will train fully here in Malawi and
      become our first batch of home-grown doctors.

PMID- 27895841
TI  - Bednets and malaria in Africa.

PMID- 27895842
TI  - Postoperative outcome of caesarean sections and other major emergency obstetric
      surgery by clinical officers and medical officers in Malawi.
AB  - BACKGROUND: Clinical officers perform much of major emergency surgery in Malawi,
      in the absence of medical officers. The aim of this study was to validate the
      advantages and disadvantages of delegation of major obstetric surgery to non
      doctors. METHODS: During a three month period, data from 2131 consecutive
      obstetric surgeries in 38 district hospitals in Malawi were collected
      prospectively. The interventions included caesarean sections alone and those that
      were combined with other interventions such as subtotal and total hysterectomy
      repair of uterine rupture and tubal ligation. All these surgeries were conducted
      either by clinical officers or by medical officers. RESULTS: During the study
      period, clinical officers performed 90% of all straight caesarean sections, 70%
      of those combined with subtotal hysterectomy, 60% of those combined with total
      hysterectomy and 89% of those combined with repair of uterine rupture. A
      comparable profile of patients was operated on by clinical officers and medical
      officers, respectively. Postoperative outcomes were almost identical in the two
      groups in terms of maternal general condition - both immediately and 24 hours
      postoperatively - and regarding occurrence of pyrexia, wound infection, wound
      dehiscence, need for re-operation, neonatal outcome or maternal death.
      CONCLUSIONS: Clinical officers perform the bulk of emergency obstetric operations
      at district hospitals in Malawi. The postoperative outcomes of their procedures
      are comparable to those of medical officers. Clinical officers constitute a
      crucial component of the health care team in Malawi for saving maternal and
      neonatal lives given the scarcity of physicians.

PMID- 27895843
TI  - Severe anemia in Malawian children.
AB  - BACKGROUND: Severe anemia is a major cause of sickness and death in African
      children, yet the causes of anemia in this population have been inadequately
      studied. METHODS: We conducted a case-control study of 381 preschool children
      with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757
      preschool children without severe anemia in urban and rural settings in Malawi.
      Causal factors previously associated with severe anemia were studied. The data
      were examined by multivariate analysis and structural equation modeling. RESULTS:
      Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9),
      malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds
      ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection
      (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD-202/-376 genetic
      disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency
      (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency
      (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe
      anemia. Folate deficiency, sickle cell disease, and laboratory signs of an
      abnormal inflammatory response were uncommon. Iron deficiency was not prevalent
      in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was
      negatively associated with bacteremia. Malaria was associated with severe anemia
      in the urban site (with seasonal transmission) but not in the rural site (where
      malaria was holoendemic). Seventy-six percent of hookworm infections were found
      in children under 2 years of age. CONCLUSIONS: There are multiple causes of
      severe anemia in Malawian preschool children, but folate and iron deficiencies
      are not prominent among them. Even in the presence of malaria parasites,
      additional or alternative causes of severe anemia should be considered.

PMID- 27895844
TI  - Effect of human rotavirus vaccine on severe diarrhea in African infants.
AB  - BACKGROUND: Rotavirus is the most common cause of severe gastroenteritis among
      young children worldwide. Data are needed to assess the efficacy of the rotavirus
      vaccine in African children. METHODS: We conducted a randomized, placebo
      controlled, multicenter trial in South Africa (3166 infants; 64.1% of the total)
      and Malawi (1773 infants; 35.9% of the total) to evaluate the efficacy of a live,
      oral rotavirus vaccine in preventing severe rotavirus gastroenteritis. Healthy
      infants were randomly assigned in a 1:1:1 ratio to receive two doses of vaccine
      (in addition to one dose of placebo) or three doses of vaccine - the pooled
      vaccine group - or three doses of placebo at 6, 10, and 14 weeks of age. Episodes
      of gastroenteritis caused by wild-type rotavirus during the first year of life
      were assessed through active follow-up surveillance and were graded with the use
      of the Vesikari scale. RESULTS: A total of 4939 infants were enrolled and
      randomly assigned to one of the three groups; 1647 infants received two doses of
      the vaccine, 1651 infants received three doses of the vaccine, and 1641 received
      placebo. Of the 4417 infants included in the per-protocol efficacy analysis,
      severe rotavirus gastroenteritis occurred in 4.9% of the infants in the placebo
      group and in 1.9% of those in the pooled vaccine group (vaccine efficacy, 61.2%;
      95% confidence interval, 44.0 to 73.2). Vaccine efficacy was lower in Malawi than
      in South Africa (49.4% vs. 76.9%); however, the number of episodes of severe
      rotavirus gastroenteritis that were prevented was greater in Malawi than in South
      Africa (6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year).
      Efficacy against all-cause severe gastroenteritis was 30.2%. At least one serious
      adverse event was reported in 9.7% of the infants in the pooled vaccine group and
      in 11.5% of the infants in the placebo group. CONCLUSIONS: Human rotavirus
      vaccine significantly reduced the incidence of severe rotavirus gastroenteritis
      among African infants during the first year of life. (ClinicalTrials.gov number,
      NCT00241644.).

PMID- 27895845
TI  - A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults.
AB  - BACKGROUND: Streptococcus pneumoniae is a leading and serious coinfection in
      adults with human immunodeficiency virus (HIV) infection, particularly in Africa.
      Prevention of this disease by vaccination with the current 23-valent
      polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further
      option for protection, but data on their clinical efficacy in adults are needed.
      METHODS: In this double-blind, randomized, placebo-controlled clinical efficacy
      trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in
      predominantly HIV-infected Malawian adolescents and adults who had recovered from
      documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks
      apart. The primary end point was a further episode of pneumococcal infection
      caused by vaccine serotypes or serotype 6A. RESULTS: From February 2003 through
      October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV
      seropositive) for 798 person-years of observation. There were 67 episodes of
      pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24
      patients, there were 19 episodes that were caused by vaccine serotypes and 5
      episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in
      the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95%
      confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the
      vaccine group and 63 in the placebo group (hazard ratio in the vaccine group,
      1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days
      after vaccination was significantly lower in the vaccine group than in the
      placebo group (3 vs. 17, P = 0.002), and the number of minor adverse events was
      significantly higher in the vaccine group (41 vs. 13, P = 0.003). CONCLUSIONS:
      The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from
      recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A.
      (Current Controlled Trials number, ISRCTN54494731.).

PMID- 27895846
TI  - Antibiotics as part of the management of severe acute malnutrition.
AB  - BACKGROUND: Severe acute malnutrition contributes to 1 million deaths among
      children annually. Adding routine antibiotic agents to nutritional therapy may
      increase recovery rates and decrease mortality among children with severe acute
      malnutrition treated in the community. METHODS: In this randomized, double-blind,
      placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months
      of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or
      placebo for 7 days in addition to ready-to-use therapeutic food for the
      outpatient treatment of uncomplicated severe acute malnutrition. The primary
      outcomes were the rate of nutritional recovery and the mortality rate. RESULTS: A
      total of 2767 children with severe acute malnutrition were enrolled. In the
      amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the
      children recovered, respectively (relative risk of treatment failure with placebo
      vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk
      with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for
      the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death
      with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with
      placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64). Among children who recovered,
      the rate of weight gain was increased among those who received antibiotics. No
      interaction between type of severe acute malnutrition and intervention group was
      observed for either the rate of nutritional recovery or the mortality rate.
      CONCLUSIONS: The addition of antibiotics to therapeutic regimens for
      uncomplicated severe acute malnutrition was associated with a significant
      improvement in recovery and mortality rates. (Funded by the Hickey Family
      Foundation and others; ClinicalTrials.gov number, NCT01000298.).

PMID- 27895847
TI  - Efficacy of a low-cost bubble CPAP system in treatment of respiratory distress in
      a neonatal ward in Malawi.
AB  - BACKGROUND: Respiratory failure is a leading cause of neonatal mortality in the
      developing world. Bubble continuous positive airway pressure (bCPAP) is a safe,
      effective intervention for infants with respiratory distress and is widely used
      in developed countries. Because of its high cost, bCPAP is not widely utilized in
      low-resource settings. We evaluated the performance of a new bCPAP system to
      treat severe respiratory distress in a low resource setting, comparing it to
      nasal oxygen therapy, the current standard of care. METHODS: We conducted a non
      randomized convenience sample study to test the efficacy of a low-cost bCPAP
      system treating newborns with severe respiratory distress in the neonatal ward of
      Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g
      and presenting with severe respiratory distress who fulfilled inclusion criteria
      received nasal bCPAP if a device was available; if not, they received standard
      care. Clinical assessments were made during treatment and outcomes compared for
      the two groups. FINDINGS: 87 neonates (62 bCPAP, 25 controls) were recruited.
      Survival rate for neonates receiving bCPAP was 71.0% (44/62) compared with 44.0%
      (11/25) for controls. 65.5% (19/29) of very low birth weight neonates receiving
      bCPAP survived to discharge compared to 15.4% (1/13) of controls. 64.6% (31/48)
      of neonates with respiratory distress syndrome (RDS) receiving bCPAP survived to
      discharge, compared to 23.5% (4/17) of controls. 61.5% (16/26) of neonates with
      sepsis receiving bCPAP survived to discharge, while none of the seven neonates
      with sepsis in the control group survived. INTERPRETATION: Use of a low-cost
      bCPAP system to treat neonatal respiratory distress resulted in 27% absolute
      improvement in survival. The beneficial effect was greater for neonates with very
      low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could
      reduce neonatal mortality in developing countries.

PMID- 27895848
TI  - Four artemisinin-based treatments in African pregnant women with malaria.
AB  - BACKGROUND: Information regarding the safety and efficacy of artemisinin
      combination treatments for malaria in pregnant women is limited, particularly
      among women who live in sub-Saharan Africa. METHODS: We conducted a multicenter,
      randomized, open-label trial of treatments for malaria in pregnant women in four
      African countries. A total of 3428 pregnant women in the second or third
      trimester who had falciparum malaria (at any parasite density and regardless of
      symptoms) were treated with artemether-lumefantrine, amodiaquine-artesunate,
      mefloquine-artesunate, or dihydroartemisinin-piperaquine. The primary end points
      were the polymerase-chain-reaction (PCR)-adjusted cure rates (i.e., cure of the
      original infection; new infections during follow-up were not considered to be
      treatment failures) at day 63 and safety outcomes. RESULTS: The PCR-adjusted cure
      rates in the per-protocol analysis were 94.8% in the artemether-lumefantrine
      group, 98.5% in the amodiaquine-artesunate group, 99.2% in the dihydroartemisinin
      piperaquine group, and 96.8% in the mefloquine-artesunate group; the PCR-adjusted
      cure rates in the intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and
      95.5%, respectively. There was no significant difference among the amodiaquine
      artesunate group, dihydroartemisinin-piperaquine group, and the mefloquine
      artesunate group. The cure rate in the artemether-lumefantrine group was
      significantly lower than that in the other three groups, although the absolute
      difference was within the 5-percentage-point margin for equivalence. The
      unadjusted cure rates, used as a measure of the post-treatment prophylactic
      effect, were significantly lower in the artemether-lumefantrine group (52.5%)
      than in groups that received amodiaquine-artesunate (82.3%), dihydroartemisinin
      piperaquine (86.9%), or mefloquine-artesunate (73.8%). No significant difference
      in the rate of serious adverse events and in birth outcomes was found among the
      treatment groups. Drug-related adverse events such as asthenia, poor appetite,
      dizziness, nausea, and vomiting occurred significantly more frequently in the
      mefloquine-artesunate group (50.6%) and the amodiaquine-artesunate group (48.5%)
      than in the dihydroartemisinin-piperaquine group (20.6%) and the artemether
      lumefantrine group (11.5%) (P<0.001 for comparison among the four groups).
      CONCLUSIONS: Artemether-lumefantrine was associated with the fewest adverse
      effects and with acceptable cure rates but provided the shortest posttreatment
      prophylaxis, whereas dihydroartemisinin-piperaquine had the best efficacy and an
      acceptable safety profile. (Funded by the European and Developing Countries
      Clinical Trials Partnership and others; ClinicalTrials.gov number, NCT00852423.).

PMID- 27895850
TI  - Evaluation of hepatitis C virus intrafamilial transmission among families with
      one index case, a pilot study from Fars province, Iran.
AB  - AIM: Our aim was to survey the rate and risk factors for Hepatitis C virus
      interfamilial transmission among families with one index case. BACKGROUND: The
      role of intrafamilial transmission in Hepatitis C virus epidemiology is still
      debated. PATIENTS AND METHODS: A cross-sectional study was conducted on 34
      families (236 members) of HCV infected patients from Fars province, spring to
      summer 2013. All subjects were first evaluated for the risk factors of exposure
      and then their serum was checked for the presence of HCV antibody and the genome,
      using ELISA and PCR. The genotype of all PCR positive cases was also determined
      by a commercial assay. Two independent sample t test and Chi-Square test were
      used to compare groups together. RESULTS: In 18 out of 34 families, HCV antibody
      was detected (52.9%) in new members. Among them, HCV transmission in 11 families
      (32%) was also confirmed by PCR. Having a history of intravenous drug abuse
      (P=0.006) and incarceration (P=0.01) showed to be important risk factors for
      interfamilial transmission. Hence, blade/needle sharing (P=0.016) just following
      molecular assay and sex (P=036) only in the serologic analysis were also
      determined as significant risk factors. Furthermore, based on serologic results,
      medium socioeconomic state was further associated with this manner of
      transmission (P=0.019 and P=0.328). Interestingly, among relatives, 13 cases were
      brothers while just 5 cases were couples. The genotypes 3a and 1a were more
      prevalent among the population. CONCLUSION: In conclusion, our finding
      highlighted a noticeable role of interfamilial transmission for HCV spread and
      supports the significant role of close relatives, especially brother relationship
      in this spread. Hence, the socioeconomic state was associated with the
      transmission rate of virus in the family.

PMID- 27895849
TI  - Celiac disease and obstetrical-gynecological contribution.
AB  - Celiac disease (CD) shows an increased prevalence in female, particularly during
      the fertile period. Celiac disease should be researched in infertility,
      spontaneous and recurrent abortions, delayed menarche, amenorrhea, early
      menopause, and children with low birth-weight. Celiac disease is still little
      considered during the evaluation of infertility. Up to 50% of women with
      untreated CD refer an experience of miscarriage or an unfavorable outcome of
      pregnancy. Celiac patients taking a normal diet (with gluten) have a shorter
      reproductive period. Women with undiagnosed CD had a higher risk of small for
      gestation age infants very small for gestational age infants and pre-term birth
      when compared with women with noted CD. The link between NCGS and infertility is
      actually unknown. The goal of our work is to perform an actual review about this
      topic and to increase the awareness in the medical population to research celiac
      disease in selected obstetric and gynecological disorders.

PMID- 27895851
TI  - Evaluating the safety, efficacy and complications of electrotherapy and its
      comparison with conventional method of hemorrhoidectomy.
AB  - AIM: This study was performed to evaluate the efficacy, safety and complications
      of electrotherapy compared with conventional hemorrhoidectomy (Ferguson
      technique). BACKGROUND: Ferguson hemorrhoidectomy is always associated with
      considerable pain and postoperative complications. Still, the electrotherapy
      method in which the hemorrhoidal tissue is not removed may not improve critical
      complications. PATIENTS AND METHODS: This randomized clinical trial was performed
      on patients with hemorrhoids referring to hospitals affiliated to the Kerman
      University of Medical Sciences during 2014-2015. One hundred and twenty patients
      presented with symptomatic hemorrhoids grade I, II, III, and IV were randomized
      into two groups. Group 1 (60 patients) underwent electrotherapy using 30 mA
      direct current and group 2 (60 patients) were submitted to Ferguson
      hemorrhoidectomy. The groups were compared regarding postoperative pain severity
      and complications, including recurrent symptoms, infection and recovery time to
      return to normal activities. The p<= 0.05 was considered statistically
      significant. RESULTS: More than 70% of patients in group 2 complained of severe
      pain, but in group 1, no more than 30% of patients experienced severe pain up to
      6 hours post-surgery and 70% complained of mild pain 2-3 days post-surgery.
      Twenty four-hour hospitalization in group 2 and group 1 were 97% and 78%,
      respectively, whilst patients in electrotherapy group could be treated as
      outpatients. The mean return time to usual activities was 15 and 1.5 days for
      group 2 and 1, respectively. CONCLUSION: Electrotherapy with a direct current of
      30 mA significantly reduce postoperative pain and the recovery period. This
      method showed a good success rate and less complication than the Ferguson method.
      As a result, because of more effectiveness, less pain, as well as shorter
      recovery time and getting back to normal activities, we recommend this procedure
      for the treatment of symptomatic hemorrhoids grade I, II, and III.

PMID- 27895852
TI  - Protein-protein interaction network of celiac disease.
AB  - AIM: The aim of this study is to investigate the Protein-Protein Interaction
      Network of Celiac Disease. BACKGROUND: Celiac disease (CD) is an autoimmune
      disease with susceptibility of individuals to gluten of wheat, rye and barley.
      Understanding the molecular mechanisms and involved pathway may lead to the
      development of drug target discovery. The protein interaction network is one of
      the supportive fields to discover the pathogenesis biomarkers for celiac disease.
      MATERIAL AND METHODS: In the present study, we collected the articles that
      focused on the proteomic data in celiac disease. According to the gene expression
      investigations of these articles, 31 candidate proteins were selected for this
      study. The networks of related differentially expressed protein were explored
      using Cytoscape 3.3 and the PPI analysis methods such as MCODE and ClueGO.
      RESULTS: According to the network analysis Ubiquitin C, Heat shock protein 90kDa
      alpha (cytosolic and Grp94); class A, B and 1 member, Heat shock 70kDa protein,
      and protein 5 (glucose-regulated protein, 78kDa), T-complex, Chaperon in
      containing TCP1; subunit 7 (beta) and subunit 4 (delta) and subunit 2 (beta),
      have been introduced as hub-bottlnecks proteins. HSP90AA1, MKKS, EZR, HSPA14,
      APOB and CAD have been determined as seed proteins. CONCLUSION: Chaperons have a
      bold presentation in curtail area in network therefore these key proteins beside
      the other hub-bottlneck proteins may be a suitable candidates biomarker panel for
      diagnosis, prognosis and treatment processes in celiac disease.

PMID- 27895853
TI  - Expression of liver alpha-amylase in obese mouse hepatocytes.
AB  - AIM: The aim of this study is to demonstrate the relation between the expression
      of liver alpha-amylase and obesity. BACKGROUND: Alpha-amylase catalyses the
      hydrolysis of 1, 4-alpha-glucosidic linkages in polysaccharides and has three
      main subtypes, including: salivary, pancreatic, and hepatic. Hepatic alpha
      amylase is involved in glycogen metabolism, and has a role in obesity and its
      management. In this study, we aimed to analyze the expression of liver alpha
      amylase in overweight and obese mouse. MATERIAL AND METHODS: In this study, NMRI
      male mice were randomly divided into two groups. The sample group (obese) took a
      high-fat and carbohydrate diet, while the control group (normal) took a
      laboratory pellet chow for eight weeks. During this period, their weight was
      measured. After eight weeks, liver hepatocytes were isolated using an enzymatic
      digestion method. Immunocytochemistry (ICC) and flow cytometry analysis were
      performed to measure alpha amylase protein expression in mouse liver hepatocyte
      cells. RESULTS: A significant difference in the body weight was observed between
      the two groups (p<0.05). The qualitative protein expression of liver alpha
      amylase was found to be higher in the obese group in both tests
      (immunocytochemistry and flow cytometry). Animals from the test group presented
      higher alpha-amylase expression, which suggests that this hepatic protein may
      constitute a potential indicator of susceptibility for fat tissue accumulation
      and obesity. The present data demonstrates an increased expression of liver
      amylase in obese mice. CONCLUSION: These results suggest that liver amylase
      secretion might be useful for predicting susceptibility to obesity induced by
      consumption of a high-fat and carbohydrate diet.

PMID- 27895854
TI  - Differential expression of aristaless-like homeobox 4: a potential marker for
      gastric adenocarcinoma.
AB  - AIM: The objective of this experiment was to evaluate the ALX-4 mRNA expression
      level in different stages of human gastric adenocarcinoma compared to the gastric
      cancer stem cells (GCSC) and gastric cancer cell line, MKN-45. BACKGROUND:
      Gastric cancer is the second most common cancer in the world today, leading
      approximately to 3-10% of all cancer-related deaths. Identification of specific
      biomarkers could be a crucial approach to improve diagnosis and treatment of this
      cancer type. Recent findings emphasized on the up-regulation of Aristaless-Like
      Homeobox 4 (ALX-4) gene expression in several tumors. MATERIAL AND METHODS: MKN
      45 cell culture was prepared, and gastric cancer stem cell (GCSC) isolation was
      performed by flowcytometry. Then, 37 fresh gastric tissue samples from cancer
      patient were subjected for expression analysis by quantitative RT-PCR, prior to
      any therapeutic intervention in the comparative study for evaluation of ALX-4
      gene expression. RESULTS: GCSCs with cuboidal shape as well as a positive
      expression of CD105, CD44, CD90 and negative for CD45, CD34 markers were
      identified. Overexpression of ALX-4 was detected in 46% (3.351+/-2.94, P<0.05) of
      gastric cancer tissue specimens and GCSCs (4.31+/-0.04, P<0.005). The mRNA
      expression level of ALX-4 in MKN-45 gastric cancer cell line was 2.81+/-0.07
      (P<0.005). We determined that ALX-4 mRNA level significantly correlated with the
      tumor grade (P=0.004), stage (p=0.000153), but not gender (P= 0.06). CONCLUSION:
      These results documented the important role of ALX-4 in GCSCs, as an oncogene in
      progressive cancer, and valuable target in the treatment of drug resistant
      tumors.

PMID- 27895855
TI  - Years of life lost due to gastric cancer is increased after Bayesian correcting
      for misclassification in Iranian population.
AB  - AIM: To estimate the change in years of life lost (YLL) due to gastric cancer
      mortality after correcting for misclassification in registering causes of death
      using the Bayesian method. BACKGROUND: For evaluating the health status of a
      country and determining priority of risk factors, some epidemiologic indicators
      are needed. Due to premature death, YLL is one of the most widely used
      indicators. To have an exact estimate of YLL, an accurate death registry data is
      needed, but the Iranian death registry is subject to misclassification error.
      MATERIAL AND METHODS: Gastric cancer mortality data from 2006 to 2010 for Iran
      were extracted from national death statistics. The rate of misclassification in
      registered causes of deaths was estimated, using Bayesian method for each year.
      Then YLL of gastric cancer is estimated for different age-sex categories before
      and after implementing Bayesian method. RESULTS: Using Bayesian method, the
      estimated misclassification rate for gastric cancer in cancer without label group
      were 5%, 3%, 3%, 7% and 7% respectively from 2006 to 2010. Estimated Years of
      life lost due to gastric cancer before correcting misclassification were
      respectively 111684.93, 114957.31, 112391.93, 112250.53 and 113300.92 person
      years for years 2006 to 2010. After correcting misclassification, the total YLL
      of gastric cancer increased to 1535.19, 921.11, 908.39, 2566.39 and 2507.00
      person-years, respectively from 2006 to 2010. CONCLUSION: If health policy makers
      ignore the existence of misclassification in registered causes of death, they may
      underestimate the burden of some causes of death and overestimate some others.

PMID- 27895856
TI  - Genetic characterization of Cryptosporidium spp. among patients with
      gastrointestinal complaints.
AB  - AIM: This study investigated subtypes of Cryptosporidium in patients with
      gastrointestinal complaints in Tehran, Iran. BACKGROUND: Cryptosporidium, an
      intracellular protozean parasite, is among the major causative agents of
      gastroenteritis disorders in humans. It also causes water-borne and food-borne
      outbreaks of diarrheal diseases. PATIENTS AND METHODS: A total of 1685 fecal
      samples were collected from patients with gastrointestinal complaints who had
      been referred to clinical laboratories Tehran, Iran. The primary diagnosis was
      established by the detection of oocysts using the modified Ziehl-Neelsen staining
      method and following that, the positive microscopically samples were selected for
      sequence analysis of the partial 60 kDa glycoprotein (gp60) gene. RESULTS: Out of
      1685 collected samples, 7 (0.4 %) were positive for Cryptosporidium oocysts.
      Sequence analysis of gp60 gene in seven Cryptosporidium isolates revealed that
      two subtype families were identified, IIa and IId. Five (of 7) isolates belonged
      to the subtype family IIa and the remaining two isolates belonged to IId. Two sub
      types were recognized within the subtype family II,a including IIaA16G2R1 (3/5),
      IIaA17G1R1 (2/5), while IIdA17G1d was the only subtype within IId subtype family.
      CONCLUSION: The predominance of zoonotic subtype families of C. parvum species
      (IIa, IId) in this study highlights the importance of zoonotic transmission of
      cryptosporidiosis in the country.

PMID- 27895857
TI  - Frequency of VanA, VanB and VanH variants amongst vancomycin-resistant
      enterococci isolated from patients in central region of Iran.
AB  - AIM: The aim of this study was to investigate the VRE frequency and the rate of
      each gene in isolated enterococci from patients with intestinal infection in the
      central region of Iran. BACKGROUND: Enterococci infections are a public health
      growing concern due to the glycopeptide antibiotics resistance especially
      vancomycin. Genes, vanA, B, and H contribute to the influence of vancomycin
      resistant enterococci (VRE). PATIENTS AND METHODS: This study was conducted from
      January to July 2014 in Shahrood university hospital. Enterococci isolation and
      its antibacterial susceptibility were performed by culturing in Aesculin Azide
      agar and Kirby-Bauer method, respectively. Vancomycin-resistant genes were
      screened through conventional PCR, and subsequently sequenced. RESULTS: Among 265
      specimens, 100 isolates revealed enterococci, in which E. faecalis (91%) and E.
      faecium (9%). The isolated enterococci were resistant to vancomycin (6%) and
      chloramphenicol (21%), whereas their large proportions (94% to 100%) were multi
      drug resistant. All VRE isolates belonged to E. faecalis, conversely, the E.
      faecium were susceptible to the same antibiotic. Both vanA and vanH genes were
      identified in all VRE isolates, although, no vanB gene was indicated. Homology
      analysis of sequenced amplicons verified the full length compatibility to the
      worldwide reported genes. CONCLUSION: The present study revealed VR E.faecalis in
      gastroenteritis patients and resistance factor for vanA and vanH genes are
      coordinated. Since enterococci isolates were all multidrug resistance, increase
      in VR E.faecalis vanA / vanH in this area could be expected.

PMID- 27895858
TI  - Distribution of pathogenicity island (PAI) markers and phylogenetic groups in
      diarrheagenic and commensal Escherichia coli from young children.
AB  - AIM: This case-control study investigated the various PAI markers, phylogenetic
      groups and antimicrobial susceptibility among DEC and commensal E. coli isolates.
      BACKGROUND: Diarrheagenic Escherichia coli (DEC) is an emerging agent among
      pathogens that cause diarrheal diseases and represents a major public health
      problem in developing countries. The major difference in virulence among DEC
      pathotype and commensals may be related to the presence of specific genomic
      segments, termed pathogenicity islands (PAIs). PATIENTS AND METHODS: A total of
      600 stool specimens from children (450 with and 150 without diarrhea) were
      collected and various PAI markers, phylogenetic groups and antimicrobial
      resistance profile among DEC and commensal E. coli isolates were detected.
      RESULTS: One hundred sixty eight (90.3%) isolates were resistant to one or more
      antimicrobial agents. PAI markers were detected in a substantial percentage of
      commensal (90%) and DEC isolates (99.3%) (P> 0.05). The most prevalent PAI marker
      among DEC and commensal isolates was HPI (91.9% DEC vs. 68% commensal). We found
      a high number of PAI markers such as SHI-2, She and LEE that were significantly
      associated with DEC. Several different combinations of PAIs were found among DEC
      isolates. Comparison of PAIs among DEC and commensal isolates showed that many
      DEC isolates (94.8%) carried two or more PAI markers, while 76% of commensals had
      only one PAI marker (P<0.05). According to the phylogenetic classification, group
      B2 was the most commonly found in the DEC isolates. Furthermore, our results
      showed that group B2 can be present in commensal isolates (18%). CONCLUSION:
      These results indicate that PAI markers are widespread among commensal and DEC
      isolates and these commensal isolates may be reservoirs for transmission of these
      markers.

PMID- 27895859
TI  - Dysbiosis of fecal microbiota and high frequency of Citrobacter, Klebsiella spp.,
      and Actinomycetes in patients with irritable bowel syndrome and gastroenteritis.
AB  - AIM: This study was aimed to characterize putative differences of fecal
      microbiota between irritable bowel syndrome (IBS) and gastroenteritis patients
      and healthy controls. BACKGROUND: New evidence proposed that gut microbiota has a
      deep effect on the balance between health and disease. PATIENTS AND METHODS: The
      presence of Clostridium difficile, Campylobacter spp., Enterobacteriacea and
      Staphylococci were detected in the samples using selective and specific culture
      media. Microscopic examination of the samples was done to detect Actinomycetes,
      yeasts, Bifidobacteria, Fusobacterium spp., as well as white blood cells, red
      blood cells, mucus and epithelial cells. RESULTS: Results of this study showed
      relatively higher frequency of Citrobacter spp., Lactobacilli, and Actinomycetes
      in the IBS patients. Elevated levels of WBC, RBC secretion, and increased amounts
      of Klebsiella, Escherichia coli and Citrobacter spp. were characterized in the
      patients with gastroenteritis compared with the control group. CONCLUSION:
      Depletion of gram positive cocci and gram negative bacilli also suggested
      dysbiosis of intestinal microbiota in these patients.

PMID- 27895860
TI  - Hydatid liver cyst causing portal vein thrombosis and cavernous transformation: a
      case report and literature review.
AB  - A 33-year-old male with abdominal distention after meals was admitted to the
      hospital. He had a history of surgery for hydatid liver cyst. The cyst was
      located at the liver hilum and there were portal venous thrombosis and cavernous
      transformation. It had been treated with partial cystectomy, omentoplasty and
      albendazole. Two years later at the admission to our center, his laboratory tests
      were in normal ranges. Abdominal imaging methods revealed splenomegaly, portal
      vein thrombosis, cavernous transformation and the previously operated hydatid
      liver cyst. Upper gastrointestinal endoscopy demonstrated esophageal and gastric
      fundal varices. Due to his young age and low risk for surgery, the patient was
      planned for surgical treatment of both pathologies at the same time. At
      laparotomy, hydatid liver cyst was obliterated with omentum and there was no sign
      of active viable hydatid disease. A meso-caval shunt with an 8 mm in-diameter
      graft was created. In the postoperative period, his symptoms and endoscopic
      varices were regressed. There were four similar cases reported in the literature.
      This one was the youngest and the only one treated by a surgical shunt. Hydatid
      liver cysts that located around the hilum can lead to portal vein thrombosis and
      cavernous thrombosis. Treatment should consist of both hydatid liver cyst and
      portal hypertension. To the best of our knowledge, this was the first case of
      surgically treated portal vein thrombosis that was originated from a hydatid
      liver cyst.

PMID- 27895861
TI  - An unusual cause of anemia in cirrhosis: spur cell anemia, a case report with
      review of literature.
AB  - Chronic anemia is common in liver cirrhosis. In this setting, the pathogenesis of
      anemia is complex and multifactorial. Spur cell anemia is a serious disorder in
      cirrhotic patients and is associated with poor prognosis. Liver transplantation
      constitutes the only therapeutic tool. We report a case with severe spur cell
      anemia in alcoholic liver cirrhosis. In the attempt to investigate the origin of
      the disorder, we have evaluated the lipoprotein profile and found a significant
      reduction of apolipoprotein AI and HDL3 subclass as a possible cause of the
      disease.

PMID- 27895862
TI  - Cutaneous angiosarcoma metastatic to small bowel with nodal involvement.
AB  - A 77-year-old male with a history of metastatic scalp angiosarcoma presented with
      intractable gastrointestinal bleeding from a jejunal mass detected on capsule
      endoscopy. He underwent laparoscopic-assisted resection of the mass.
      Intraoperatively, an isolated small bowel mass with bulky lymphadenopathy was
      seen and resected en bloc. Pathology showed a 6.8cm high-grade metastatic
      angiosarcoma with nodal involvement and negative margins. Angiosarcoma is a
      sarcoma with a grim prognosis. The incidence is 2% of all soft tissue sarcomas;
      cutaneous lesions comprise 27% of manifestations and usually appear on head and
      neck. Risk factors include lymphedema, neurofibromatosis, vinyl chloride,
      arsenic, and anabolic steroids. Overall 5-year survival is 30-35% and is higher
      in patients younger than 60, those without metastasis, tumors less than 5 cm, and
      favorable histology. Angiosarcoma metastasis to small bowel is rare but nodal
      involvement is even more unusual, reported only three times in the literature.
      This case is the first with nodal involvement to present at a resectable stage.
      To diagnose disease when still at a resectable stage, a high index of suspicion
      must be maintained with any gastrointestinal symptoms in a patient with a history
      of angiosarcoma. Laparoscopic-assisted resection is safe for the resection of
      small bowel angiosarcoma.

PMID- 27895863
TI  - Small bowel pigmentation.

PMID- 27895864
TI  - Is it necessary to screen Helicobacter pylori infection in patients with celiac
      disease and iron deficiency?

PMID- 27895865
TI  - Assessment of Independent Risk Factors of Developing Pneumothorax During
      Percutaneous Core Needle Lung Biopsy: Focus on Lesion Depth.
AB  - BACKGROUND: Previous studies identifying risk factors for pneumothorax in
      percutaneous core needle lung biopsies reported inconsistent and contradictory
      results. OBJECTIVES: We aimed to identify independent risk factors for
      pneumothorax associated with computed tomography (CT)-guided percutaneous core
      needle lung biopsy (PCNB). PATIENTS AND METHODS: We retrospectively reviewed 591
      biopsy procedures for focal lung lesions. Risk factors for pneumothorax as a
      complication after lung biopsy were determined by univariate and multivariate
      analyses of variables including the patient's age, gender, lesion depth from the
      pleural surface, lesion size, lesion location, presence or absence of fissure
      crossing by the needle, emphysema in the same lobe where the biopsy was
      performed, and the final diagnosis of the biopsy lesion. RESULTS: Pneumothorax
      occurred in 100 (16.9%) of 591 procedures. Based on univariate analyses,
      significant risk factors affecting the incidence of pneumothorax were patient
      gender (P = 0.039), lesion depth from the pleural surface (P < 0.001), fissure
      crossing by the needle (P = 0.002), and the presence of emphysema (P = 0.009).
      From the multivariate analysis, an increased rate of pneumothorax was strongly
      correlated with lesion depth from the pleural surface (odds ratio [OR], 1.71; 95%
      confidence interval [CI], 1.50 - 1.96; P < 0.001) and the presence of emphysema
      (OR, 2.95; 95% CI, 1.73 - 5.04; P < 0.001). CONCLUSION: Lesion depth from the
      pleural surface and the presence of emphysema were strongly correlated with the
      increasing incidence of pneumothorax after CT-guided PCNB. Our results may be
      applicable for the risk management of PCNBs to reduce pneumothorax as a
      complication.

PMID- 27895866
TI  - Liver Findings in Patients with Hereditary Hemorrhagic Telangiectasia.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT), also known as Osler
      Weber-Rendu syndrome, is a rare autosomal dominant genetic vascular dysplasia.
      OBJECTIVES: The aim is to characterize the liver involvement of HHT by multi
      detector helical computed tomography. PATIENTS AND METHODS: Through the use of
      multi-detector helical computed tomography, scan data derived from 12 cases of
      HHT were retrospectively studied, and an abdominal scan was performed on all of
      the patients. RESULTS: (i) Three types of shunting were found in the livers,
      including arteriovenous (hepatic artery to hepatic vein) in 6 cases,
      arterioportal (hepatic artery to portal vein) in 2 cases, and portal venous
      (portal vein to hepatic vein) in 4 cases, (ii) Biliary diseases were detected in
      8 cases, including 3 cases of bilomas accompanied by increases of alkaline
      phosphatase (mean 271 units, ranging from 152 to 479 units) and arteriovenous
      shunts, and the other 5 cases revealed slight biliary dilation with no increase
      of alkaline phosphates, but were instead accompanied by arteriovenous shunts (3
      cases) and portal venous shunts (2 cases). (iii) Vascular anatomic variants were
      observed in 4 cases, including 3 with accompanying arteriovenous shunts and 1
      with accompanying arterioportal shunting. CONCLUSION: The involved liver with HHT
      typically shows vascular shunting and biliary diseases. Also, arteriovenous
      shunts may be vulnerable to biliary diseases.

PMID- 27895868
TI  - Immunohistochemical Subtypes of Breast Cancer: Correlation with
      Clinicopathological and Radiological Factors.
AB  - BACKGROUND: The relationship between biomarkers and imaging features is important
      because imaging findings can predict molecular features. OBJECTIVES: To
      investigate the relationship between clinicopathologic and radiologic factors and
      the immunohistochemical (IHC) profiles associated with breast cancer. PATIENTS
      AND METHODS: From December 2004 to September 2013, 200 patients (mean age, 56
      years; range, 29 - 82 years) were diagnosed with breast cancer and underwent
      surgery at our institution. Their medical records were reviewed to determine age,
      symptom presence, mammographic findings (including mass, asymmetry,
      microcalcifications, or negativity), sonographic Breast Imaging-Reporting and
      Data System (BI-RADS) category, pathologic type of cancer (invasive ductal,
      mucinous, medullary, or papillary carcinoma), histologic grade, T-stage, and IHC
      subtypes. Based on the IHC profiles, tumor subtypes were classified as luminal A,
      luminal B, human epidermal growth factor receptor 2 (HER2) enriched, or triple
      negative (TN) cancers. Using univariate and multivariate logistic regression
      analyses, we looked for correlations between four IHC subtypes and two IHC
      subtypes (TN and non-triple negative [non-TN]) and clinicopathologic and
      radiologic factors, respectively. RESULTS: Based on our univariate analyses with
      the four subtypes, the TN subtype showed a higher incidence of masses on
      mammography compared to the other subtypes (P = 0.037), and the TN subtype also
      tended to have the highest histologic grade among the subtypes (P < 0.001). With
      regard to the two IHC subtypes, the TN subtype had a significant association with
      medullary cancer (P = 0.021), higher histologic grade (grade 3; P < 0.001), and
      higher T stage (T2; P = 0.027) compared to the non-TN subtypes. In a multivariate
      logistic regression analysis of the clinicoradiologic factors compared to luminal
      A, the HER2 subtype had a significant association with BI-RADS category 4b (odds
      ratio [OR], 9.005; 95% confidence interval [CI], 1.414 - 57.348; P = 0.020) and
      borderline significance with category 4c (OR, 4.669; 95% CI, 0.970 - 22.468; P =
      0.055). In a multivariate logistic regression analysis of the clinicoradiologic
      factors associated with the non-TN subtypes, the TN subtype was significantly
      correlated with medullary carcinoma (OR, 7.092; 95% CI, 1.149 - 43.772; P =
      0.035). CONCLUSION: These results suggest that patients with the TN subtypes are
      more likely to have higher-histologic-grade tumors and medullary cancer. The HER2
      subtype was typically associated with a higher BI-RADS category.

PMID- 27895867
TI  - Detection of Second Mesiobuccal Canals in Maxillary First Molars Using a New
      Angle of Cone Beam Computed Tomography.
AB  - BACKGROUND: The localization of the additional canal orifice is one of the
      primary factors influencing the success of endodontic treatment. To deal with
      this problem, several techniques that each have their own advantages and
      disadvantages have been discussed in the literature. OBJECTIVES: The aim of the
      present in vitro study was to review a new approach to localizing second
      mesiobuccal (MB2) canals in maxillary first molars using cone beam computed
      tomography (CBCT). PATIENTS AND METHODS: The CBCT scans of 296 patients who were
      referred to the department of dentomaxillofacial radiology were included in the
      study. The presence of MB2 canals, the angle formed by the mesiobuccal,
      distobuccal, and palatal root canal orifices (?MDP), and the angle formed by the
      mesiobuccal, distobuccal, and MB2 canal orifices (?MDMB2) were evaluated on the
      axial section. Pearson correlation and multiple linear regression methods were
      used for all predictions. All of the analyses were performed using SPSS for
      windows version 22.0. A two-sided P value < 0.05 was defined as statistically
      significant. RESULTS: Of the 468 first molars, MB2 canals were observed in 296
      subjects (141 females and 155 males). There were no statistically significant
      differences between females and males (P = 0.300). The ?MDP and ?MDMB2 were
      detected and evaluated. A moderate positive correlation was found between the
      ?MDP and the ?MDMB2. To predict the ?MDMB2 values, it was shown that the ?MDMB2
      increased by 0.420 degrees when the ?MDP increased by 1 degree. If the ?MDP was
      greater than 90.95 degrees, there was a 78% probability that MB2 canals could be
      found. CONCLUSION: The determination of the presence of MB2 in the maxillary
      first molars may be carried out using CBCT scans. If the ?MDP was 91 degrees or
      greater, there was considered to be a higher probability that MB2 canals would be
      found in the endodontic cavity. Due to the positive correlation between the ?MDP
      and the ?MDMB2, the localization of MB2 canals may be easily performed in
      relation to the main MB canal.

PMID- 27895869
TI  - Assessing Absorption Coefficient of Hemoglobin in the Breast Phantom Using Near
      Infrared Spectroscopy.
AB  - BACKGROUND: Blood concentrations and oxygen saturation levels are important
      biomarkers for breast cancer diagnosis. OBJECTIVES: In this study, the absorption
      coefficient of hemoglobin (Hb) was used to distinguish between normal and
      abnormal breast tissue. MATERIALS AND METHODS: A near-infrared source (637 nm)
      was transmitted from major and minor vessels of a breast phantom containing 2*,
      4* concentrations of oxy- and deoxy-Hb. The absorption coefficients were
      determined from spectrometer (SM) and powermeter (PM) data. RESULTS: The
      absorption coefficients were 0.075 +/- 0.026 cm-1 for oxygenated Hb (normal) in
      major vessels and 0.141 +/- 0.023 cm-1 at 4* concentration (abnormal) with SM,
      whereas the breast absorption coefficients were 0.099 +/- 0.017 cm-1 for
      oxygenated Hb (normal) in minor vessels and 0.171 +/- 0.005 cm-1 at 4*
      concentrations with SM. A comparison of the data obtained using a SM and a PM was
      not significant statistically. CONCLUSION: The study of the absorption
      coefficient data of different concentrations of Hb in normal and abnormal breasts
      via the diffusion of near-infrared light is a valuable method and has the
      potential to aid in early detection of breast abnormalities with SM and PM in
      major and minor vessels.

PMID- 27895870
TI  - Systolic Compression of a Myocardial Bridged Coronary Artery and its Morphologic
      Characteristics: A Combination Study of Computed Tomography Angiography and
      Invasive Angiography.
AB  - BACKGROUND: Myocardial bridging (MB) is a congenital anomaly in which a segment
      of a major epicardial coronary artery courses through the myocardium. This
      anomaly can lead to myocardial ischemia, arrhythmia, and even death. The
      effectiveness of coronary computed tomographic angiography (CCTA) in the
      detection of MB and its morphological features, and the accuracy of invasive
      coronary angiography (ICA) in the evaluation of systolic compression have been
      shown in some prior studies. OBJECTIVES: The present study aimed to evaluate the
      correlation between the depth and the length of MB as determined using CCTA, and
      the degree of luminal narrowing of the involved tunneled segment as calculated
      using the ICA. PATIENTS AND METHODS: For this study, 109 consecutive patients
      diagnosed with myocardial bridging using CCTA, and who had already undergone ICA,
      were studied. The depth and length of the MB was determined in the CCTA, while
      the degree of systolic compression was calculated in the ICA. The correlation
      between the depth and length of the MB and the systolic compression were then
      evaluated. RESULTS: The degree of systolic compression was found to be correlated
      with the depth of the MB. However, there was no correlation between the length of
      the MB and the degree of systolic compression. CONCLUSION: The systolic
      compression of the MB was influenced by the depth of the tunneled segment, not by
      its length.

PMID- 27895871
TI  - Desmoid Tumor of the Chest Wall Mimicking Recurrent Breast Cancer: Multimodality
      Imaging Findings.
AB  - Desmoid tumor of breast is a rare benign, locally aggressive tumor with a high
      recurrence rate. It has been associated with scar from previous breast surgery or
      trauma. Especially in breast cancer patients with previous operation history, it
      may simulate recurrent breast cancer clinically and radiologically. We presented
      multimodality imaging findings (ultrasound, computed tomography, magnetic
      resonance imaging and positron emission tomography/computed tomography) of chest
      wall desmoid tumor mimicking recurrent breast cancer in a 38-year-old patient
      with a history of left modified mastectomy. The desmoid tumor is a rare benign
      tumor that should be considered in the differential diagnosis of malignant local
      tumor recurrence after breast cancer operation. Biopsy was required for accurate
      diagnosis and wide local excision was its appropriate surgical management.

PMID- 27895872
TI  - Investigation of Factors Affecting Body Temperature Changes During Routine
      Clinical Head Magnetic Resonance Imaging.
AB  - BACKGROUND: Pulsed radiofrequency (RF) magnetic fields, required to produce
      magnetic resonance imaging (MRI) signals from tissue during the MRI procedure
      have been shown to heat tissues. OBJECTIVES: To investigate the relationship
      between body temperature rise and the RF power deposited during routine clinical
      MRI procedures, and to determine the correlation between this effect and the
      body's physiological response. PATIENTS AND METHODS: We investigated 69 patients
      from the Korean national cancer center to identify the main factors that
      contribute to an increase in body temperature (external factors and the body's
      response) during a clinical brain MRI. A routine protocol sequence of MRI scans
      (1.5 T and 3.0 T) was performed. The patient's tympanic temperature was recorded
      before and immediately after the MRI procedure and compared with changes in
      variables related to the body's physiological response to heat. RESULTS: Our
      investigation of the physiological response to RF heating indicated a link
      between increasing age and body temperature. A higher increase in body
      temperature was observed in older patients after a 3.0-T MRI (r = 0.07, P = 0.29
      for 1.5-T MRI; r = 0.45, P = 0.002 for 3.0-T MRI). The relationship between age
      and body heat was related to the heart rate (HR) and changes in HR during the MRI
      procedure; a higher RF power combined with a reduction in HR resulted in an
      increase in body temperature. CONCLUSION: A higher magnetic field strength and a
      decrease in the HR resulted in an increase in body temperature during the MRI
      procedure.

PMID- 27895873
TI  - Value of Computerized Tomography Enterography in Predicting Crohn's Disease
      Activity: Correlation with Crohn's Disease Activity Index and C-Reactive Protein.
AB  - BACKGROUND: The accurate evaluation of Crohn's disease activity is important for
      the treatment of the disease and for monitoring the response. Computerized
      tomography (CT) enterography is a useful imaging modality that reflects enteric
      inflammation, as well as extramural complications. OBJECTIVES: The aim of this
      study was to evaluate the correlation between CT enterographic (CTE) findings of
      active Crohn's disease and the Crohn's disease activity index (CDAI) and C
      reactive protein (CRP). PATIENTS AND METHODS: Fifty CT enterographies of 39
      patients with Crohn's disease in the small bowel were used in our study. The CDAI
      was assessed through clinical and laboratory variables. Multiple CT parameters,
      including mural hyperenhancement, mural thickness, mural stratification, comb
      sign, and mesenteric fat attenuation, were evaluated with a four-point scale. The
      presence or absence of enhanced lymph nodes, fibrofatty proliferation, sinus or
      fistula, abscess, and stricture were also assessed. Two gastrointestinal
      radiologists independently reviewed all CT images, and inter-observer agreement
      was examined. Correlations between CT findings, CRP, and CDAI were assessed using
      Spearman's rank correlation and logistic regression analysis. To assess the
      predictive accuracy of the model, a receiver-operating characteristic curve
      analysis for the sum of CT enterographic scores was used. RESULTS: Mural
      hyperenhancement, mural thickness, comb sign, mesenteric fat density, and
      fibrofatty proliferation were significantly correlated with CDAI and CRP (P <
      0.05). The binary logistic regression model demonstrated that mesenteric fat
      density, mural stratification, and the presence of enhanced lymph nodes (P <
      0.05) had an influence on CDAI severity. The area under the receiver operating
      characteristic curve (AUROC) of the CTE index for predicting disease activity was
      0.85. Using a cut-off value of 8, the sensitivity and negative predictive values
      were 95% and 94%, respectively. CONCLUSION: Most CTE findings correlated with
      CDAI and CRP in patients with active Crohn's disease.

PMID- 27895874
TI  - Computerized Tomography and Magnetic Resonance Imaging Findings in Malignant
      Perivascular Epithelioid Cell Tumors of the Ovaries with Pulmonary Metastasis.
AB  - Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor composed
      of immunohistochemically and histologically distinctive perivascular epithelioid
      cells. Here, we report on the computed tomography (CT) and magnetic resonance
      imaging (MRI) findings of ovarian PEComa with pulmonary metastasis. The tumor was
      visible as a multilocular hemorrhagic mass that encased the ovarian vessels.
      These findings were different to those of other common ovarian tumors.

PMID- 27895875
TI  - Takeaways from Pre-Contrast T1 and T2 Breast Magnetic Resonance Imaging in Women
      with Recently Diagnosed Breast Cancer.
AB  - BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE - MRI) has
      been widely used in the management of breast cancer, and its diagnostic value in
      breast imaging has been demonstrated. There have only been a few reports
      regarding the usefulness of pre-contrast imaging. Knowledge about clinically
      significant findings of preoperative, pre-contrast T1 and T2 MR images will allow
      more accurate decisions regarding patient treatment and management. OBJECTIVES:
      The aim of this study was to evaluate the clinically significant findings of
      preoperative, pre-contrast T1 and T2 MR images in recently diagnosed breast
      cancer patients. PATIENTS AND METHODS: We analyzed 390 preoperative 3-T MRIs of
      recently diagnosed breast cancer patients in whom the diagnosis was confirmed by
      a core needle biopsy. RESULTS: MRI findings that were correlated with post-core
      needle-biopsy changes were observed in 27.9% of the pre-contrast T1 and T2 MRIs
      (n = 109/390). Two of 35 cases that had a subareolar ductal high signal area on
      the pre-contrast T1 were confirmed by surgery as having nipple-areolar complex
      involvement. CONCLUSION: A subareolar ductal high signal area on a pre-contrast
      T1 MRI must be carefully assessed in combination with dynamic, contrast-enhanced
      images for proper surgical management.

PMID- 27895877
TI  - Unexplained Cardiac Arrest After Near Drowning in a Young Experienced Swimmer:
      Insight from Cardiovascular Magnetic Resonance Imaging.
AB  - Cardiac magnetic resonance imaging (cMRI) is a well-established noninvasive
      imaging modality in clinical cardiology. Its ability to provide tissue
      characterization make it well suited for the study of patients with cardiac
      diseases. We describe a multi-modality imaging evaluation of a 45-year-old man
      who experienced a near drowning event during swimming. We underline the unique
      capability of tissue characterization provided by cMRI, which allowed detection
      of subtle, clinically unrecognizable myocardial damage for understanding the
      causes of sudden cardiac arrest and also showed the small damages caused by
      cardiopulmonary resuscitation.

PMID- 27895876
TI  - Assessment of Mean Glandular Dose in Mammography System with Different Anode
      Filter Combinations Using MCNP Code.
AB  - BACKGROUND: X-ray mammography is one of the general methods for early detection
      of breast cancer. Since glandular tissue in the breast is sensitive to radiation
      and it increases the risk of cancer, the given dose to the patient is very
      important in mammography. OBJECTIVES: The aim of this study was to determine the
      average absorbed dose of X-ray radiation in the glandular tissue of the breast
      during mammography examinations as well as investigating factors that influence
      the mean glandular dose (MGD). One of the precise methods for determination of
      MGD absorbed by the breast is Monte Carlo simulation method which is widely used
      to assess the dose. MATERIALS AND METHODS: We studied some different X-ray
      sources and exposure factors that affect the MGD. "Midi-future" digital
      mammography system with amorphous-selenium detector was simulated using the Monte
      Carlo N-particle extended (MCNPX) code. Different anode/filter combinations such
      as tungsten/silver (W/Ag), tungsten/rhodium (W/Rh), and rhodium/aluminium (Rh/Al)
      were simulated in this study. The voltage of X-ray tube ranged from 24 kV to 32
      kV with 2 kV intervals and the breast phantom thickness ranged from 3 to 8 cm,
      and glandular fraction g varied from 10% to 100%. RESULTS: MGD was measured for
      different anode/filter combinations and the effects of changing tube voltage,
      phantom thickness, combination and glandular breast tissue on MGD were studied.
      As glandular g and X-ray tube voltage increased, the breast dose increased too,
      and the increase of breast phantom thickness led to the decrease of MGD. The
      obtained results for MGD were consistent with the result of Boone et al. that was
      previously reported. CONCLUSION: By comparing the results, we saw that W/Rh
      anode/filter combination is the best choice in breast mammography imaging because
      of the lowest delivered dose in comparison with W/Ag and Rh/Al. Moreover, breast
      thickness and g value have significant effects on MGD.

PMID- 27895878
TI  - Evaluation of Visibility of Foreign Bodies in the Maxillofacial Region:
      Comparison of Computed Tomography, Cone Beam Computed Tomography, Ultrasound and
      Magnetic Resonance Imaging.
AB  - BACKGROUND: Detection of foreign bodies (FBs) is challenging. Selection of a fast
      and affordable imaging modality to locate the FB with minimal patient radiation
      dose is imperative. OBJECTIVES: This study sought to compare four commonly used
      imaging modalities namely cone beam computed tomography (CBCT), magnetic
      resonance imaging (MRI), computed tomography (CT), and ultrasound (US) for
      detection of FBs in the head and neck region. MATERIALS AND METHODS: In this in
      vitro study, iron, glass, stone, wood, asphalt, and tooth samples measuring 0.1 *
      0.5 * 0.5 cm were placed in the tongue muscle, soft tissue-bone interface and
      nasal cavity in a fresh sheep's head and subjected to MRI, US, CT and CBCT. A
      total of 20 images were captured by each imaging system from the six materials in
      the afore-mentioned locations. The images were observed by an expert oral and
      maxillofacial radiologist and a general radiologist. To assess reliability, 20
      images were randomly observed by the observers in two separate sessions. The
      images were classified into three groups of good visibility, bad visibility and
      invisible. The data were analyzed using SPSS version 18, Wilcoxon Signed Rank,
      Pearson chi square, and Fisher's exact tests. RESULTS: All FBs in the tongue and
      at the soft tissue-bone interface had good visibility on US (P = 1.00). Also,
      CBCT and CT had significantly different performance regarding FB detection (P <
      0.001). All wooden samples in the nasal cavity were invisible on CT scans; while,
      only 20% of them were invisible on CBCT scans. MRI showed significant differences
      for detection of FBs in the three locations (P < 0.001). MRI could not locate
      iron samples due to severe artifacts and only showed their presence (bad
      visibility) but other FBs except for wood and tooth in the nasal cavity (100%
      invisible) had good visibility on MRI. CONCLUSIONS: Ultrasound is recommended as
      the first choice when FB is located within the superficial soft tissues with no
      bone around it. In case of penetration of FB into deeper tissues or beneath bone,
      CT or CBCT are recommended. Otherwise, considering lower dose, CBCT is preferred
      over CT. We can use MRI if the FB is not ferromagnetic. However, CT is the first
      choice in emergency situations because of higher sensitivity.

PMID- 27895879
TI  - Evaluation of Stress Scores Throughout Radiological Biopsies.
AB  - BACKGROUND: Ultrasound-guided biopsy procedures are the most prominent methods
      that increase the trauma, stress and anxiety experienced by the patients.
      OBJECTIVES: Our goal was to examine the level of stress in patients waiting for
      radiologic biopsy procedures and determine the stress and anxiety level arising
      from waiting for a biopsy procedure. PATIENTS AND METHODS: This prospective study
      included 35 female and 65 male patients who were admitted to the interventional
      radiology department of Kartal Dr. Lutfi Kirdar training and research hospital,
      Istanbul between the years 2014 and 2015. They filled out the adult resilience
      scale consisting of 33 items. Patients who were undergoing invasive radiologic
      interventions were grouped according to their phenotypic characteristics,
      education level (low, intermediate, and high), and biopsy features (including
      biopsy localization: neck, thorax, abdomen, and bone; and the number of
      procedures performed, 1 or more than 1). Before the biopsy, they were also asked
      to complete the depression-anxiety-stress scale (DASS 42), state-trait anxiety
      inventory scale (STAI-I), and continuous anxiety scale STAI-II. A total of 80
      patients were biopsied (20 thyroid and parathyroid, 20 thorax, 20 liver and
      kidney, and 20 bone biopsies). The association between education levels (primary-
      secondary, high school and postgraduate) and the number of biopsies (1 and more
      than 1) with the level of anxiety and stress were evaluated using the above
      mentioned scales. RESULTS: Evaluation of sociodemographic and statistical
      characteristics of the patients showed that patients with biopsy in the neck
      region were moderately and severely depressed and stressed. In addition, the
      ratio of severe and extremely severe anxiety scores was significantly high. While
      the STAI-I and II scores were lined up as neck > bone > thorax > abdomen, STAI-I
      was higher in neck biopsies compared to thorax and abdomen biopsies. Regarding
      STAI-I and II scales, patients with neck biopsy had the highest anxiety score.
      CONCLUSION: We believe that active briefing of patients who need to undergo neck
      and bone biopsies and have high anxiety score by healthcare personnel is an
      effective method to control psychological mood and increase the efficiency of
      treatment.

PMID- 27895880
TI  - Comparison of Open-Cell Stent and Closed-Cell Stent for Treatment of Central Vein
      Stenosis or Occlusion in Hemodialysis Patients.
AB  - BACKGROUND: Central vein stenosis or occlusion is a common complication that can
      lead to significant morbidity and dysfunction of access in the hemodialysis
      patient. More lesions can develop over time, and preserving access becomes a
      challenge as life expectancy of the hemodialysis patient increases. OBJECTIVES:
      The goal was to compare long-term results and determine the outcomes of open-cell
      stent versus closed-cell stent for central vein stenosis or occlusion in
      hemodialysis patients. PATIENTS AND METHODS: From 1997 to 2015, in 401
      hemodialysis patients, stent placement for central vein stenosis or occlusion was
      performed if balloon angioplasty was unsatisfactory, due to elastic recoil or
      occurrence of restenosis within 3 months. When thrombus was present, primary
      stenting was performed. A total of 257 open-cell stents and 144 closed-cell
      stents were used. Angiographic findings including lesion site, central vein
      stenosis or occlusion, and presence of thrombosis and complication were
      evaluated. Primary patency rate and mean patency rate of the stent were compared
      between two stent groups by Kaplan-Meier survival analysis. RESULTS: For the open
      cell stent group, 159 patients were diagnosed as central vein stenosis and 98
      were occlusion. For the closed-cell stent group, 78 were stenosis and 66 were
      occlusion. There were two complications for central migration and two for
      procedure-related vein rupture. Open-cell stents and closed-cell stents had mean
      patency rates of 10.9 +/- 0.80 months and 8.5 +/- 10.87 months, respectively (P =
      0.002). CONCLUSION: The open-cell stent is effective and its performance is
      higher than that obtained with the closed-cell stent for treating central vein
      stenosis or occlusion in hemodialysis patients.

PMID- 27895881
TI  - Morphologic Evaluation of Ductus Diverticulum Using Multi - Detector Computed
      Tomography: Comparison with Traumatic Pseudoaneurysm of the Aortic Isthmus.
AB  - OBJECTIVES: To evaluate morphologic variations at the aortic isthmus with
      particular attention to ductus diverticulum, a mimicker of traumatic
      pseudoaneurysm, and to describe differences using Computed Tomography (CT)
      images. PATIENTS AND METHODS: From December 2013 to December 2014, patients who
      underwent a chest CT examination after blunt trauma at our emergency department
      were included. Aortic isthmus morphologies were evaluated using multiplanar
      reconstruction (MPR) and maximum intensity projection (MIP) images as follows.
      Type I -concave contour, type II -convexity without a discrete bulge, or type III
      -a discrete focal bulge (defined as ductus diverticulum). RESULTS: After
      excluding 11 cases of traumatic pseudoaneurysm of the aortic isthmus, a total of
      432 trauma patients (mean age = 47.1 +/- 19.1 years, number of males = 318) were
      evaluated for aortic isthmus morphology, and classified as follows; type I (n =
      240, 55.6%), type II (n = 157, 36.3%), and type III (n = 35, 8.1%). As compared
      with traumatic pseudoaneurysm (n = 11), ductus diverticulum had a smaller
      vertical diameter (5.5 +/- 1.3 mm vs. 11.2 +/- 2.7 mm, P < 0.001), a broader base
      (14.9 +/- 4.1 mm vs. 8.8 +/- 4.5 mm, P < 0.001), a smoother margin (97.1% vs.
      27.3%, P < 0.001), and formed obtuse angle with the aortic wall. Furthermore,
      ductus diverticulum was not associated with the presence of a dissection flap or
      hemomediastinum. CONCLUSION: Ductus diverticulum, a mimicker of traumatic
      pseudoaneurysm of the aortic isthmus, is a frequently observed anatomic variant
      during CT examinations. Familiarity with its CT imaging findings could avoid it
      being confused with traumatic pseudoaneurysm in blunt trauma patients.

PMID- 27895882
TI  - Primary Pleural Synovial Sarcoma with Metastatic Cardiac Involvement: A Case
      Report.
AB  - Primary pleuropulmonary synovial sarcomas are rare soft tissue malignancies;
      combined metastatic involvement of the heart is extremely rare. In this case
      report, a 17-year-old female presented with a history of chest pain. Chest
      radiographs revealed a round mass in the left upper hemithorax, and computed
      tomography (CT) showed a well-defined heterogeneous enhancing mass abutting the
      pleura. A core needle biopsy revealed malignant spindle cells. Surgical resection
      was performed, and a final diagnosis of primary pleural synovial sarcoma,
      monophasic fibrous type, was made. The patient underwent radical irradiation and
      chemotherapy and remained stable for 28 months until a follow-up chest CT showed
      a poorly enhancing nodule in the left pericardial region that enlarged after 5
      months. Surgical resection was performed. Histological examination confirmed
      metastatic cardiac involvement from a primary pleural synovial sarcoma. We report
      this unusual case of a primary pleural synovial sarcoma metastasis to the heart.

PMID- 27895884
TI  - A Note on Drawing Conclusions in the Study of Visual Search and the Use of Slopes
      in Particular.
AB  - The slope of the set size function as a critical statistic first gained favor in
      the 1960s due in large part to the seminal papers on short-term memory search by
      Saul Sternberg and soon, many others. In the 1980s, the slope statistic reemerged
      in much the same role in visual search as Anne Treisman and again, soon many
      others brought that research topic into great prominence. This note offers the
      historical and current perspective of the present author, who has devoted a
      significant portion of his theoretical efforts to this and related topics over
      the past 50 years.

PMID- 27895883
TI  - Alexithymia, but not autism spectrum disorder, may be related to the production
      of emotional facial expressions.
AB  - BACKGROUND: A prominent diagnostic criterion of autism spectrum disorder (ASD)
      relates to the abnormal or diminished use of facial expressions. Yet little is
      known about the mechanisms that contribute to this feature of ASD. METHODS: We
      showed children with and without ASD emotionally charged video clips in order to
      parse out individual differences in spontaneous production of facial expressions
      using automated facial expression analysis software. RESULTS: Using hierarchical
      multiple regression, we sought to determine whether alexithymia (characterized by
      difficulties interpreting one's own feeling states) contributes to diminished
      facial expression production. Across groups, alexithymic traits-but not ASD
      traits, IQ, or sex-were associated with quantity of facial expression production.
      CONCLUSIONS: These results accord with a growing body of research suggesting that
      many emotion processing abnormalities observed in ASD may be explained by co
      occurring alexithymia. Developmental and clinical considerations are discussed,
      and it is argued that alexithymia is an important but too often ignored trait
      associated with ASD that may have implications for subtyping individuals on the
      autism spectrum.

PMID- 27895885
TI  - Facing the Spectator.
AB  - We investigated the familiar phenomenon of the uncanny feeling that represented
      people in frontal pose invariably appear to "face you" from wherever you stand.
      We deploy two different methods. The stimuli include the conventional one-a flat
      portrait rocking back and forth about a vertical axis-augmented with two novel
      variations. In one alternative, the portrait frame rotates whereas the actual
      portrait stays motionless and fronto-parallel; in the other, we replace the
      (flat!) portrait with a volumetric object. These variations yield exactly the
      same optical stimulation in frontal view, but become grossly different in very
      oblique views. We also let participants sample their momentary awareness through
      "gauge object" settings in static displays. From our results, we conclude that
      the psychogenesis of visual awareness maintains a number-at least two, but most
      likely more-of distinct spatial frameworks simultaneously involving "cue
      scission." Cues may be effective in one of these spatial frameworks but
      ineffective or functionally different in other ones.

PMID- 27895886
TI  - Back to the USSR: How Colors Might Shape the Political Perception of East versus
      West.
AB  - People typically process information to confirm their prior held attitudes and
      stereotypes. As the political relations between NATO and Russia have
      distinctively drifted apart in recent years, we were interested in how far old
      established color depictions referring to the Cold War's demarcations (USSR =
      red; NATO = blue) might reinforce people's political perception of an East versus
      West antagonism nowadays. Participants received a fabricated news article in
      which both world powers were either depicted on a map as Russia = red and NATO =
      blue or vice versa (Study 1). Testing a different sample in Study 2, we fully
      removed color assignments and used hachured distinctions or no distinctions at
      all. We revealed that perceived political distance between both sides increased
      particularly for participants with negative attitudes toward Russia, but only
      when Russia was depicted in red. Thus, colors referring to the old-established
      Cold War patterns can indeed shape the political perception and reinforce
      stereotypical East versus West thinking.

PMID- 27895888
TI  - In situ formation of poly(vinyl alcohol)-heparin hydrogels for mild encapsulation
      and prolonged release of basic fibroblast growth factor and vascular endothelial
      growth factor.
AB  - Heparin-based hydrogels are attractive for controlled growth factor delivery, due
      to the native ability of heparin to bind and stabilize growth factors. Basic
      fibroblast growth factor and vascular endothelial growth factor are heparin
      binding growth factors that synergistically enhance angiogenesis. Mild, in situ
      encapsulation of both basic fibroblast growth factor and vascular endothelial
      growth factor and subsequent bioactive dual release has not been demonstrated
      from heparin-crosslinked hydrogels, and the combined long-term delivery of both
      growth factors from biomaterials is still a major challenge. Both basic
      fibroblast growth factor and vascular endothelial growth factor were encapsulated
      in poly(vinyl alcohol)-heparin hydrogels and demonstrated controlled release. A
      model cell line, BaF32, was used to show bioactivity of heparin and basic
      fibroblast growth factor released from the gels over multiple days. Released
      basic fibroblast growth factor promoted higher human umbilical vein endothelial
      cell outgrowth over 24 h and proliferation for 3 days than the poly(vinyl
      alcohol)-heparin hydrogels alone. The release of vascular endothelial growth
      factor from poly(vinyl alcohol)-heparin hydrogels promoted human umbilical vein
      endothelial cell outgrowth but not significant proliferation. Dual-growth factor
      release of basic fibroblast growth factor and vascular endothelial growth factor
      from poly(vinyl alcohol)-heparin hydrogels resulted in a synergistic effect with
      significantly higher human umbilical vein endothelial cell outgrowth compared to
      basic fibroblast growth factor or vascular endothelial growth factor alone.
      Poly(vinyl alcohol)-heparin hydrogels allowed bioactive growth factor
      encapsulation and provided controlled release of multiple growth factors which is
      beneficial toward tissue regeneration applications.

PMID- 27895887
TI  - Symmetry Lasts Longer Than Random, but Only for Brief Presentations.
AB  - Previous research has shown that explicit emotional content or physical image
      properties (e.g., luminance, size, and numerosity) alter subjective duration.
      Palumbo recently demonstrated that the presence or absence of abstract
      reflectional symmetry also influenced subjective duration. Here, we explored this
      phenomenon further by varying the type of symmetry (reflection or rotation) and
      the objective duration of stimulus presentation (less or more than 1 second).
      Experiment 1 used a verbal estimation task in which participants estimated the
      presentation duration of reflection, rotation symmetry, or random square-field
      patterns. Longer estimates were given for reflectional symmetry images than
      rotation or random, but only when the image was presented for less than 1 second.
      There was no difference between rotation and random. These findings were
      confirmed by a second experiment using a paired-comparison task. This temporal
      distortion could be because reflection has positive valence or because it is
      processed efficiently be the visual system. The mechanism remains to be
      determined. We are relatively sure, however, that reflectional patterns can
      increase subjective duration in the absence of explicit semantic content, and in
      the absence of changes in the size, luminance, or numerosity in the images.

PMID- 27895889
TI  - Amino acid transporters implicated in endocytosis of Buchnera during symbiont
      transmission in the pea aphid.
AB  - BACKGROUND: Many insects host their obligate, maternally transmitted symbiotic
      bacteria in specialized cells called bacteriocytes. One of the best-studied
      insect nutritional endosymbioses is that of the aphid and its endosymbiont,
      Buchnera aphidicola. Aphids and Buchnera are metabolically and developmentally
      integrated, but the molecular mechanisms underlying Buchnera transmission and
      coordination with aphid development remain largely unknown. Previous work using
      electron microscopy to study aphid asexual embryogenesis has revealed that
      Buchnera transmission involves exocytosis from a maternal bacteriocyte followed
      by endocytotic uptake by a blastula. While the importance of exo- and endocytic
      cellular processes for symbiont transmission is clear, the molecular mechanisms
      that regulate these processes are not known. Here, we shed light on the molecular
      mechanisms that regulate Buchnera transmission and developmental integration.
      RESULTS: We present the developmental atlas of ACYPI000536 and ACYPI008904 mRNAs
      during asexual embryogenesis in the pea aphid, Acyrthosiphon pisum. Immediately
      before Buchnera invasion, transcripts of both genes were detected by whole-mount
      in situ hybridization in the posterior syncytial nuclei of late blastula embryos.
      Following Buchnera invasion, expression of both genes was identified in the
      region occupied by Buchnera throughout embryogenesis. Notably during Buchnera
      migration, expression of both genes was not concomitant with the entirety of the
      bacterial mass but rather expression colocalized with Buchnera in the anterior
      region of the bacterial mass. In addition, we found that ACYPI000536 was
      expressed in nuclei at the leading edge of the bacterial mass, joining the
      bacterial mass in subsequent developmental stages. Finally, quantitative reverse
      transcription real-time PCR suggested that early in development both transcripts
      were maternally provisioned to embryos. CONCLUSIONS: We venture that ACYPI000536
      and ACYPI008904 function as nutrient sensors at the site of symbiont invasion to
      facilitate TOR-pathway-mediated endocytosis of Buchnera by the aphid blastula.
      Our data support earlier reports of bacteriocyte determination involving a two
      step recruitment process but suggest that the second wave of recruitment occurs
      earlier than previously described. Finally, our work highlights that bacteriocyte
      enriched amino acid transporter paralogs have additionally been retained to play
      novel developmental roles in both symbiont recruitment and bacteriome
      development.

PMID- 27895890
TI  - Sex- and age-related differences in arterial pressure and albuminuria in mice.
AB  - BACKGROUND: Animal models have become valuable experimental tools for
      understanding the pathophysiology and therapeutic interventions in cardiovascular
      disease. Yet to date, few studies document the age- and sex-related differences
      in arterial pressure, circadian rhythm, and renal function in normotensive mice
      under basal conditions, across the life span. We hypothesized that mice display
      similar sex- and age-related differences in arterial pressure and renal function
      to humans. METHODS: Mean arterial pressure (MAP) and circadian rhythm of arterial
      pressure were measured over 3 days via radiotelemetry, in 3- and 5-month-old
      (adult) and 14- and 18-month-old (aged) FVB/N and in 5-month-old (adult) C57BL/6
      male and female normotensive mice. In FVB/N mice, albuminuria from 24-h urine
      samples as well as body, heart, and kidney weights were measured at each age.
      RESULTS: Twenty-four-hour MAP was greater in males than females at 3, 5, and 14
      months of age. A similar sex difference in arterial pressure was observed in
      C57BL/6 mice at 5 months of age. In FVB/N mice, 24-h MAP increased with age, with
      females displaying a greater increase between 3 and 18 months of age than males,
      such that MAP was no longer different between the sexes at 18 months of age. A
      circadian pattern was observed in arterial pressure, heart rate, and locomotor
      activity, with values for each greater during the active (night/dark) than the
      inactive (day/light) period. The night-day dip in MAP was greater in males and
      increased with age in both sexes. Albuminuria was greater in males than females,
      increased with age in both sexes, and rose to a greater level in males than
      females at 18 months of age. CONCLUSIONS: Arterial pressure and albuminuria
      increase in an age- and sex-specific manner in mice, similar to patterns observed
      in humans. Thus, mice represent a useful model for studying age and sex
      differences in the regulation of arterial pressure and renal disease.
      Understanding the mechanisms that underlie the pathophysiology of cardiovascular
      disease may lead to new and better-tailored therapies for men and women.

PMID- 27895891
TI  - Gene-specific sex effects on eosinophil infiltration in leishmaniasis.
AB  - BACKGROUND: Sex influences susceptibility to many infectious diseases, including
      some manifestations of leishmaniasis. The disease is caused by parasites that
      enter to the skin and can spread to the lymph nodes, spleen, liver, bone marrow,
      and sometimes lungs. Parasites induce host defenses including cell infiltration,
      leading to protective or ineffective inflammation. These responses are often
      influenced by host genotype and sex. We analyzed the role of sex in the impact of
      specific gene loci on eosinophil infiltration and its functional relevance.
      METHODS: We studied the genetic control of infiltration of eosinophils into the
      inguinal lymph nodes after 8 weeks of Leishmania major infection using mouse
      strains BALB/c, STS, and recombinant congenic strains CcS-1,-3,-4,-5,-7,-9,-11,
      12,-15,-16,-18, and -20, each of which contains a different random set of 12.5%
      genes from the parental "donor" strain STS and 87.5% genes from the "background"
      strain BALB/c. Numbers of eosinophils were counted in hematoxylin-eosin-stained
      sections of the inguinal lymph nodes under a light microscope. Parasite load was
      determined using PCR-ELISA. RESULTS: The lymph nodes of resistant STS and
      susceptible BALB/c mice contained very low and intermediate numbers of
      eosinophils, respectively. Unexpectedly, eosinophil infiltration in strain CcS-9
      exceeded that in BALB/c and STS and was higher in males than in females. We
      searched for genes controlling high eosinophil infiltration in CcS-9 mice by
      linkage analysis in F2 hybrids between BALB/c and CcS-9 and detected four loci
      controlling eosinophil numbers. Lmr14 (chromosome 2) and Lmr25 (chromosome 5)
      operate independently from other genes (main effects). Lmr14 functions only in
      males, the effect of Lmr25 is sex independent. Lmr15 (chromosome 11) and Lmr26
      (chromosome 9) operate in cooperation (non-additive interaction) with each other.
      This interaction was significant in males only, but sex-marker interaction was
      not significant. Eosinophil infiltration was positively correlated with parasite
      load in lymph nodes of F2 hybrids in males, but not in females. CONCLUSIONS: We
      demonstrated a strong influence of sex on numbers of eosinophils in the lymph
      nodes after L. major infection and present the first identification of sex
      dependent autosomal loci controlling eosinophilic infiltration. The positive
      correlation between eosinophil infiltration and parasite load in males suggests
      that this sex-dependent eosinophilic infiltration reflects ineffective
      inflammation.

PMID- 27895893
TI  - Downregulation of long non-coding RNA H19 promotes P19CL6 cells proliferation and
      inhibits apoptosis during late-stage cardiac differentiation via miR-19b
      modulated Sox6.
AB  - BACKGROUND: Regulating cardiac differentiation to maintain normal heart
      development and function is very important. At present, biological functions of
      H19 in cardiac differentiation is not completely clear. METHODS: To explore the
      functional effect of H19 during cardiac differentiation. Expression levels of
      early cardiac-specific markers Nkx-2.5 and GATA4, cardiac contractile protein
      genes alpha-MHC and MLC-2v were determined by qRT-PCR and western lot. The levels
      of lncRNA H19 and miR-19b were detected by qRT-PCR. We further predicted the
      binding sequence of H19 and miR-19b by online softwares starBase v2.0 and
      TargetScan. The biological functions of H19 and Sox6 were evaluated by CCK-8 kit,
      cell cycle and apoptosis assay and caspase-3 activity. RESULTS: The expression
      levels of alpha-MHC, MLC-2v and H19 were upregulated, and miR-19b was
      downregulated significantly in mouse P19CL6 cells at the late stage of cardiac
      differentiation. Biological function analysis showed that knockdown of H19
      promoted cell proliferation and inhibits cell apoptosis. H19 suppressed miR-19b
      expression and miR-19b targeted Sox6, which inhibited cell proliferation and
      promoted apoptosis in P19CL6 cells during late-stage cardiac differentiation.
      Importantly, Sox6 overexpression could reverse the positive effects of H19
      knockdown on P19CL6 cells. CONCLUSION: Downregulation of H19 promoted cell
      proliferation and inhibited cell apoptosis during late-stage cardiac
      differentiation by regulating the negative role of miR-19b in Sox6 expression,
      which suggested that the manipulation of H19 expression could serve as a
      potential strategy for heart disease.

PMID- 27895894
TI  - Social media as a platform for science and health engagement: challenges and
      opportunities.
AB  - Social media has become a major platform for debates on science and health. This
      commentary argues that while social media can present challenges to communicating
      important health matters, it can also provide health experts a unique opportunity
      to engage with and build trust among members of the public.

PMID- 27895892
TI  - Sexual dimorphism in the mast cell transcriptome and the pathophysiological
      responses to immunological and psychological stress.
AB  - BACKGROUND: Biological sex plays a prominent role in the prevalence and severity
      of a number of important stress-related gastrointestinal and immune-related
      diseases including IBS and allergy/anaphylaxis. Despite the establishment of sex
      differences in these diseases, the underlying mechanisms contributing to sex
      differences remain poorly understood. The objective of this study was to define
      the role of biological sex on mast cells (MCs), an innate immune cell central to
      the pathophysiology of many GI and allergic disorders. METHODS: Twelve-week-old
      C57BL/6 male and female mice were exposed to immunological stress (2 h of IgE
      mediated passive systemic anaphylaxis (PSA)) or psychological stress (1 h of
      restraint stress (RS)) and temperature, clinical scores, serum histamine, and
      intestinal permeability (for RS) were measured. Primary bone marrow-derived MCs
      (BMMCs) were harvested from male and female mice and analyzed for MC
      degranulation, signaling pathways, mediator content, and RNA transcriptome
      analysis. RESULTS: Sexually dimorphic responses were observed in both models of
      PSA and RS and in primary MCs. Compared with male mice, female mice exhibited
      increased clinical scores, hypothermia, and serum histamine levels in response to
      PSA and had greater intestinal permeability and serum histamine responses to RS.
      Primary BMMCs from female mice exhibited increased release of beta
      hexosaminidase, histamine, tryptase, and TNF-alpha upon stimulation with IgE/DNP
      and A23187. Increased mediator release in female BMMCs was not associated with
      increased upstream phospho-tyrosine signaling pathways or downstream Ca2+
      mobilization. Instead, increased mediator release in female MCs was associated
      with markedly increased capacity for synthesis and storage of MC granule
      associated immune mediators as determined by MC mediator content and RNA
      transcriptome analysis. CONCLUSIONS: These results provide a new understanding of
      sexual dimorphic responses in MCs and have direct implications for stress-related
      diseases associated with a female predominance and MC hyperactivity including
      irritable bowel syndrome, allergy, and anaphylaxis.

PMID- 27895896
TI  - The changing biodiversity of Alabama Drosophila: important impacts of seasonal
      variation, urbanization, and invasive species.
AB  - Global warming and anthropogenic disturbances significantly influence the
      biosphere, tremendously increasing species extinction rates. In Central Alabama,
      we analyzed Drosophilidae species composition change nearly 100 years after the
      previous survey. We found ten Drosophilid species that were not reported during
      the last major biodiversity studies, two of which are invasive pests. In
      addition, we analyzed the influence of seasonal environmental variables
      characteristic of the subtropical climate zone on Drosophila abundance and
      biodiversity. We found a significant correlation between temperature and
      abundance of total Drosophila as well as for six of the seven most represented
      species individually, with a maximum abundance at intermediate temperatures (18
      26 degrees C). In addition, temperature was positively correlated with
      biodiversity of Drosophila. Precipitation produced a significant effect on the
      abundance of five species of Drosophila, with different optima for each species,
      but did not affect overall biodiversity. We concluded that in the subtropical
      climate zone of Central Alabama, seasonal temperature and precipitation changes
      produce a significant effect on Drosophila abundance and biodiversity, while
      local land use also impacts fly abundance, contributing to an apparent shift in
      species composition over the last century. We expect global climate change and
      other anthropogenic factors to further impact Drosophila species composition in
      the subtropical climate zone into the future.

PMID- 27895897
TI  - Ancestral population reconstitution from isofemale lines as a tool for
      experimental evolution.
AB  - Experimental evolution is a powerful tool to study adaptation under controlled
      conditions. Laboratory natural selection experiments mimic adaptation in the wild
      with better-adapted genotypes having more offspring. Because the selected traits
      are frequently not known, adaptation is typically measured as fitness increase by
      comparing evolved populations against an unselected reference population
      maintained in a laboratory environment. With adaptation to the laboratory
      conditions and genetic drift, however, it is not clear to what extent such
      comparisons provide unbiased estimates of adaptation. Alternatively, ancestral
      variation could be preserved in isofemale lines that can be combined to
      reconstitute the ancestral population. Here, we assess the impact of selection on
      alleles segregating in newly established Drosophila isofemale lines. We
      reconstituted two populations from isofemale lines and compared them to two
      original ancestral populations (AP) founded from the same lines shortly after
      collection. No significant allele frequency changes could be detected between
      both AP and simulations showed that drift had a low impact compared to Pool-Seq
      associated sampling effects. We conclude that laboratory selection on segregating
      variation in isofemale lines is too weak to have detectable effects, which
      validates ancestral population reconstitution from isofemale lines as an unbiased
      approach for measuring adaptation in evolved populations.

PMID- 27895898
TI  - Nest covering in plovers: How modifying the visual environment influences egg
      camouflage.
AB  - Camouflage is one of the most widespread antipredator defences, and its
      mechanistic basis has attracted considerable interest in recent years. The
      effectiveness of camouflage depends on the interaction between an animal's
      appearance and its background. Concealment can therefore be improved by changes
      to an animal's own appearance, by behaviorally selecting an optimal background,
      or by modifying the background to better match the animal's own appearance.
      Research to date has largely focussed on the first of these mechanisms, whereas
      there has been little work on the second and almost none on the third. Even
      though a number of animal species may potentially modify their environment to
      improve individual-specific camouflage, this has rarely if ever been
      quantitatively investigated, or its adaptive value tested. Kittlitz's plovers
      (Charadrius pecuarius) use material (stones and vegetation) to cover their nests
      when predators approach, providing concealment that is independent of the
      inflexible appearance of the adult or eggs, and that can be adjusted to suit the
      local surrounding background. We used digital imaging and predator vision
      modeling to investigate the camouflage properties of covered nests, and whether
      their camouflage affected their survival. The plovers' nest-covering materials
      were consistent with a trade-off between selecting materials that matched the
      color of the eggs, while resulting in poorer nest pattern and contrast matching
      to the nest surroundings. Alternatively, the systematic use of materials with
      high-contrast and small-pattern grain sizes could reflect a deliberate disruptive
      coloration strategy, whereby high-contrast material breaks up the telltale
      outline of the clutch. No camouflage variables predicted nest survival. Our study
      highlights the potential for camouflage to be enhanced by background
      modification. This provides a flexible system for modifying an animal's
      conspicuousness, to which the main limitation may be the available materials
      rather than the animal's appearance.

PMID- 27895899
TI  - Oxidatively Degradable Poly(thioketal urethane)/Ceramic Composite Bone Cements
      with Bone-Like Strength.
AB  - Synthetic bone cements are commonly used in orthopaedic procedures to aid in bone
      regeneration following trauma or disease. Polymeric cements like PMMA provide the
      mechanical strength necessary for orthopaedic applications, but they are not
      resorbable and do not integrate with host bone. Ceramic cements have a chemical
      composition similar to that of bone, but their brittle mechanical properties
      limit their use in weight-bearing applications. In this study, we designed
      oxidatively degradable, polymeric bone cements with mechanical properties
      suitable for bone tissue engineering applications. We synthesized a novel
      thioketal (TK) diol, which was crosslinked with a lysine triisocyanate (LTI)
      prepolymer to create hydrolytically stable poly(thioketal urethane)s (PTKUR) that
      degrade in the oxidative environment associated with bone defects. PTKUR films
      were hydrolytically stable for up to 6 months, but degraded rapidly (<1 week)
      under simulated oxidative conditions in vitro. When combined with ceramic micro-
      or nanoparticles, PTKUR cements exhibited working times comparable to calcium
      phosphate cements and strengths exceeding those of trabecular bone. PTKUR/ceramic
      composite cements supported appositional bone growth and integrated with host
      bone near the bone-cement interface at 6 and 12 weeks post-implantation in rabbit
      femoral condyle plug defects. Histological evidence of osteoclast-mediated
      resorption of the cements was observed at 6 and 12 weeks. These findings
      demonstrate that a PTKUR bone cement with bone-like strength can be selectively
      resorbed by cells involved in bone remodeling, and thus represent an important
      initial step toward the development of resorbable bone cements for weight-bearing
      applications.

PMID- 27895901
TI  - Prevention of hospital-acquired pneumonia in non-ventilated adult patients: a
      narrative review.
AB  - BACKGROUND: Pneumonia is one of the leading hospital-acquired infections
      worldwide and has an important impact. Although preventive measures for
      ventilator-associated pneumonia (VAP) are well known, less is known about
      appropriate measures for prevention of hospital-acquired pneumonia (HAP). AIM:
      The purpose of this narrative review is to provide an overview of the current
      standards for preventing HAP in non-ventilated adult patients. METHODS: A search
      of the literature up to May 2015 was conducted using Medline for guidelines
      published by national professional societies or professional medical
      associations. In addition, a comprehensive search for the following preventive
      measures was performed: hand hygiene, oral care, bed position, mobilization,
      diagnosis and treatment of dysphagia, aspiration prevention, viral infections and
      stress bleeding prophylaxis. FINDINGS: Regarding international guidelines,
      several measures were recommended for VAP, whilst no specific recommendations for
      HAP prevention in non-ventilated patients are available. There is reasonable
      evidence available that oral care is associated with a reduction in HAP. Early
      mobilization interventions, swift diagnosis and treatment of dysphagia, and
      multimodal programmes for the prevention of nosocomial influenza cross-infection,
      have a positive impact on HAP reduction. The impact of bed position and stress
      bleeding prophylaxis remains uncertain. Systematic antibiotic prophylaxis for HAP
      prevention should be avoided. CONCLUSION: Scant literature and little guidance is
      available for the prevention of HAP among non-ventilated adult patients. In
      addition, the criteria used for the diagnosis of HAP and the populations targeted
      in the studies selected are heterogeneous. Oral care was the most studied measure
      and was commonly associated with a decrease in HAP rate, although a broad range
      of interventions are proposed. No robust evidence is available for other
      measures. Further high-quality studies are required to evaluate the impact of
      specific measures on HAP prevention in non-ventilated adult patients.

PMID- 27895902
TI  - Effect of beta-Lactamase inhibitors on in vitro activity of beta-Lactam
      antibiotics against Burkholderia cepacia complex species.
AB  - BACKGROUND: Bacteria belonging to the Burkholderia cepacia complex (Bcc) are an
      important cause of chronic respiratory tract infections in cystic fibrosis
      patients. Intrinsic resistance to a wide range of antimicrobial agents, including
      a variety of beta-lactam antibiotics, is frequently observed in Bcc strains.
      Resistance to beta-lactams is most commonly mediated by efflux pumps, alterations
      in penicillin-binding proteins or the expression of beta-lactamases. beta
      lactamase inhibitors are able to restore the in vitro activity of beta-lactam
      molecules against a variety of Gram-negative species, but the effect of these
      inhibitors on the activity of beta-lactam treatment against Bcc species is still
      poorly investigated. METHODS: In the present study, the susceptibility of a panel
      of Bcc strains was determined towards the beta-lactam antibiotics ceftazidime,
      meropenem, amoxicillin, cefoxitin, cefepime and aztreonam; alone or in
      combination with a beta-lactamase inhibitor (clavulanic acid, sulbactam,
      tazobactam and avibactam). Consequently, beta-lactamase activity was determined
      for active beta-lactam/beta-lactamase inhibitor combinations. RESULTS: Clavulanic
      acid had no effect on minimum inhibitory concentrations, but addition of
      sulbactam, tazobactam or avibactam to ceftazidime, amoxicillin, cefoxitin,
      cefepime or aztreonam leads to increased susceptibility (at least 4-fold MIC
      decrease) in some Bcc strains. The effect of beta-lactamase inhibitors on beta
      lactamase activity is both strain- and/or antibiotic-dependent, and other
      mechanisms of beta-lactam resistance (besides production of beta-lactamases)
      appear to be important. CONCLUSIONS: Considerable differences in susceptibility
      of Bcc strains to beta-lactam antibiotics were observed. Results obtained in the
      present study suggest that resistance of Bcc strains against beta-lactam
      antibiotics is mediated by both beta-lactamases and non-beta-lactamase-mediated
      resistance mechanisms.

PMID- 27895903
TI  - Deliberate exposure of humans to chlorine-the aftermath of Ebola in West Africa.
AB  - BACKGROUND: During the recent Ebola outbreak, spraying of the environment and
      humans, including healthcare workers, with chlorine was wide spread in affected
      African countries; adverse clinical effects are reported here. METHODS: A cross
      sectional survey by interview of 1550 volunteers consisting of 500 healthcare
      workers (HCW), 550 Ebola survivors (EVD) and 500 quarantined asymptomatic Ebola
      contacts (NEVD) was conducted. Demographics, frequency of exposure to chlorine,
      clinical condition after chlorine exposure particularly eye, respiratory and skin
      conditions were noted. The length of time HCWs worked in Ebola Treatment Units
      (ETU), and use of personal protective equipment was recorded. Verbal consent was
      obtained from all participants and all responses remained anonymous. Permission
      and assistance from the guardian or parent was sought for those below 18 years of
      age. RESULTS: 493/500 HCW, 550/550 EVD and 477/500 NEVD were sprayed at least
      once with 0 . 5 % chlorine. Following even a single exposure, an increase in the
      number of eye (all three groups) and respiratory symptoms (in HCW & EVD) was
      reported (p < 0 . 001); after multiple exposure, respiratory and skin symptoms
      increased. In HCW, multiple vs single exposure was associated with an increase in
      respiratory (OR = 32 (95 % CI 22 -49) p < 0.001), eyes (OR = 30 (95 % CI 21 -43)
      p < 0.001) and skin conditions (OR = 22 (95 % CI 15-32) p < 0.001). The available
      personal protective equipment neither reduced nor prevented the adverse effects
      of chlorine. CONCLUSION: Reported exposure to chlorine has usually been
      accidental. Despite the lack of evidence as a recognised outbreak control
      measure, deliberate exposure of humans to chlorine spray was wide spread in
      Africa during the Ebola epidemic resulting in serious detrimental health effects
      on humans. We strongly recommend that this practice be banned and that
      alternative safer methods be used.

PMID- 27895895
TI  - Allergy immunotherapy across the life cycle to promote active and healthy ageing:
      from research to policies: An AIRWAYS Integrated Care Pathways (ICPs) programme
      item (Action Plan B3 of the European Innovation Partnership on active and healthy
      ageing) and the Global Alliance against Chronic Respiratory Diseases (GARD), a
      World Health Organization GARD research demonstration project.
AB  - Allergic diseases often occur early in life and persist throughout life. This
      life-course perspective should be considered in allergen immunotherapy. In
      particular it is essential to understand whether this al treatment may be used in
      old age adults. The current paper was developed by a working group of AIRWAYS
      integrated care pathways for airways diseases, the model of chronic respiratory
      diseases of the European Innovation Partnership on active and healthy ageing (DG
      CONNECT and DG Sante). It considered (1) the political background, (2) the
      rationale for allergen immunotherapy across the life cycle, (3) the unmet needs
      for the treatment, in particular in preschool children and old age adults, (4)
      the strategic framework and the practical approach to synergize current
      initiatives in allergen immunotherapy, its mechanisms and the concept of active
      and healthy ageing.

PMID- 27895904
TI  - Poor adherence to guidelines for preventing central line-associated bloodstream
      infections (CLABSI): results of a worldwide survey.
AB  - BACKGROUND: Central line-associated bloodstream infections (CLABSI) are a cause
      of increased morbidity and mortality, and are largely preventable. We documented
      attitudes and practices in intensive care units (ICUs) in 2015 in order to assess
      compliance with CLABSI prevention guidelines. METHODS: Between June and October
      2015, an online questionnaire was made available to medical doctors and nurses
      working in ICUs worldwide. We investigated practices related to central line (CL)
      insertion, maintenance and measurement of CLABSI-related data following the SHEA
      guidelines as a standard. We computed weighted estimates for high, middle and low
      income countries using country population as a weight. Only countries providing
      at least 10 complete responses were included in these estimates. RESULTS: Ninety
      five countries provided 3407 individual responses; no low income, 14 middle
      income (MIC) and 27 high income (HIC) countries provided 10 or more responses. Of
      the total respondents, 80% (MIC, SE = 1.5) and 81% (HIC, SE = 1.0) reported
      availability of written clinical guidelines for CLABSI prevention in their ICU;
      23% (MIC,SE = 1.7) and 62% (HIC,SE = 1.4) reported compliance to the following
      (combined) recommendations for CL insertion: hand hygiene, full barrier
      precaution, chlorhexidine >0.5%, no topic or systemic antimicrobial prophylaxis;
      60% (MIC,SE = 2.0) and 73% (HIC,SE = 1.2) reported daily assessment for the need
      of a central line. Most considered CLABSI measurement key to quality improvement,
      however few were able to report their CLABSI rate. Heterogeneity between
      countries was high and country specific results are made available. CONCLUSIONS:
      This study has identified areas for improvement in CLABSI prevention practices
      linked to CL insertion and maintenance. Priorities for intervention differ
      between countries.

PMID- 27895905
TI  - Outcomes of laparoscopic sleeve gastrectomy at a bariatric unit in South Africa.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity over the
      years as a standalone procedure. In 2014, it was the most rapidly growing
      bariatric procedure. The aim of this study was to describe the outcomes of LSG at
      a single bariatric unit in Johannesburg, South Africa, using the Bariatric
      Analysis and Reporting Outcome System (BAROS) standardised scoring. METHODS: A
      retrospective record review and analysis was carried out using data collected
      from patients who had LSGs. The information obtained included patient
      demographics, comorbidities, preoperative weight and height, operative technique,
      time and complications, postoperative gastrografin swallow results, hospital
      stay, and weight at 6 months postoperatively. The percentage of excess body mass
      index (BMI) loss (%EBMIL) was calculated at 6 months, and included in the BAROS
      questionnaire completed by the patients at the 6-month follow-up visit.
      Statistical significance was set at p < 0.05. RESULTS: A total of 103 patients
      were included in the study; of these, 85.4% were female and 14.6% were male. The
      mean preoperative BMI was 42.1 kg/m2; additionally, 77.7% of the patients in the
      study had comorbidities prior to the procedure. The mean operative time was 104.3
      min, with a mean hospital stay of 2.5 days. No mortalities occurred, and a
      complication rate of 7.7% was encountered. At the 6-month follow-up, the mean
      %EBMIL was 65%. When followed up at 6 months, all 103 patients demonstrated no
      failures according to the BAROS assessment. It was found that 96.1% had good,
      very good or excellent outcomes. In total, 9.7% of the patients had an excellent
      outcome. CONCLUSIONS: LSG was shown to produce an adequate %EBMIL loss at 6
      months, resulting in a significant improvement in the quality of life (QoL),
      coupled with good BAROS outcomes. The results of this research are comparable to
      other studies of LSGs, and the low complication rate supports the use of the
      procedure and accounts for no observed mortality.

PMID- 27895900
TI  - Nutritional implications for ultra-endurance walking and running events.
AB  - This paper examines the various nutritional challenges which athletes encounter
      in preparing for and participating in ultra-endurance walking and running events.
      Special attention is paid to energy level, performance, and recovery within the
      context of athletes' intake of carbohydrate, protein, fat, and various vitamins
      and minerals. It outlines, by way of a review of literature, those factors which
      promote optimal performance for the ultra-endurance athlete and provides
      recommendations from multiple researchers concerned with the nutrition and
      performance of ultra-endurance athletes. Despite the availability of some
      research about the subject, there is a paucity of longitudinal material which
      examines athletes by nature and type of ultra-endurance event, gender, age, race,
      and unique physiological characteristics. Optimal nutrition results in a
      decreased risk of energy depletion, better performance, and quicker full
      recovery.

PMID- 27895906
TI  - Respiratory distress associated with heterotopic gastrointestinal cysts of the
      oral cavity: A case report.
AB  - Heterotopic gastrointestinal cysts of the oral cavity are benign lesions usually
      discovered during infancy. Their pathogenesis is not very clear. They are rare
      congenital anomalies that result from remnants of foregut-derived epithelium in
      the head, neck, thorax or abdomen during embryonic development. The majority of
      these lesions occur in the anterior ventral surface of the tongue and extend to
      the floor of the mouth. They are confused clinically by surgeons in cases of head
      and neck masses in children as ranulas, dermoid and thyroglossal cysts, and
      lymphangioma. We report the case of a 28-day newborn with a 3.6 cm oval mass on
      the floor of the mouth causing difficulty eating and cyanosis during crying.
      Complete surgical excision was performed by an oral approach under general
      anesthesia. Microscopic examination revealed gastric epithelium with tall
      columnar mucous cells on the surface and numerous short closed crypts, resembling
      fundal glands and mature gastric epithelium.

PMID- 27895907
TI  - Succinct guide to liver transplantation for medical students.
AB  - Literature on liver transplantation for use in medical education is limited and
      as yet unsatisfactory. The aim of this article is to help medical students gain
      enough insight into the reality of being a liver transplant recipient. This is
      crucial so in the future they can feel confident in approaching these patients
      with adequate knowledge and confidence. The knowledge-tree based learning core
      topics are designed for a 2-h class including indication/contraindication in the
      real-world setting, model for end stage liver disease scoring and organ
      allocation policy, liver transplantation for hepatic malignancy, transplantation
      surgery, immunosuppression strategy in practical consideration, and management of
      viral hepatitis. The rationales of each topic are discussed comprehensively for
      better understanding by medical students. Recipient candidates may have
      reversible contraindications that halt the surgery temporarily and therefore, it
      warrants re-evaluation before transplant. Organ allocation policy is primarily
      based on disease severity instead of waiting time. Transplant surgery usually
      involves resection of the whole liver, in situ implantation with reconstruction
      of the hepatic vein, the portal vein, the hepatic artery and the biliary duct in
      sequence. The primary goal of artificial immunosuppression is to prevent graft
      rejection, and the secondary one is to reduce its complication or side effects.
      Life-long oral nucleoside/nucleotide analogues against hepatitis virus B is
      needed while short course of direct acting agents against hepatitis viral C is
      enough to eradicate the virus. Basic understanding of the underlying rationales
      will help students prepare for advanced learning and cope with the recipients
      confidently in the future.

PMID- 27895908
TI  - Diathermy awareness among surgeons-An analysis in Ireland.
AB  - INTRODUCTION: Diathermy is an integral part of many modern surgical procedures.
      While diathermy is generally accepted as 'safe', electrosurgery-induced injuries
      are among the more common causes for malpractice litigation. The purpose of this
      study was to evaluate the awareness among surgeons of the principles, risks,
      precautions and appropriate use of diathermy. METHODS: All surgeons employed from
      Senior House Officer (SHO) to Consultant grade in two teaching hospitals were
      surveyed. Sixty-three surgeons were asked to complete an anonymous questionnaire,
      which recorded level of training and addressed competence in principles, hazards,
      and precautions to be taken with diathermy. RESULTS: Eight Consultants, 5
      Specialist Registrars, 19 Registrars and 13 SHO's responded (71% response). All
      but three subspecialties were represented. Eighty-two percent (37/45) had no
      formal diathermy training. Despite 89% (40/45) of surgeons regarding diathermy as
      a safe instrument, 56% felt they had inadequate understanding of the principles
      and failed to demonstrate an appropriate awareness of the potential risks. Fifty
      seven percent exhibited a dangerous lack of awareness in managing equipment not
      yielding the desired effect and 22% were unaware of any patient groups requiring
      special caution. Only 42% wanted formal training. CONCLUSION: Our results show a
      dearth of awareness among surgeons regarding diathermy. Given our findings, we
      urge a shift in attitude towards diathermy, with surgeons adopting a more
      cautious and safe approach to diathermy use. We recommend that formal training be
      introduced as a hospital based initiative.

PMID- 27895909
TI  - Retained surgical items after abdominal and pelvic surgery: Incidence, trend and
      predictors- observational study.
AB  - INTRODUCTION: Surgical retained items (RSIs) are associated with increase in
      perioperative morbidity and mortality. We used a large national database to
      investigate the incidence, trends and possible predictors for RSIs after major
      abdominal and pelvic procedures. METHODS: The nationwide inpatient sample data
      were queried to identify patients who underwent major abdominal and pelvic
      procedures and discharged with secondary ICD-9-CM diagnosis code of (998.44 and
      998.7). McNemar's tests and conditional logistic regression analyses of a 1:1
      matched sample were conducted to explore possible predictive factors for RSI.
      RESULTS: RSI incidence rate was 13 in 100,000 cases-years from 2007 to 2011 after
      major abdominal and pelvic procedures. RSI incidence remained steady over the
      five-year study period. Rural hospitals and elective procedures were associated
      with a higher RSI incidence rate [(OR 1.391, 95% CL 1.056-1.832), p = 0.019] and
      [(OR 1.775, 95%CL 1.501-2.098), p < 0.001] respectively. CONCLUSIONS: Our study
      was able to add more to the epidemiological perspective and the risk profile of
      retained surgical items in abdominal and pelvic surgery. Surgical cases
      associated with these factors may need further testing to rule out RSI.

PMID- 27895911
TI  - Under-five mortality among displaced populations in Meheba refugee camp, Zambia,
      2008-2014.
AB  - BACKGROUND: Under-five mortality, which is the probability of a child dying
      before their fifth birthday, is of concern in Zambia as infant and child
      mortality rates are important social indicators. Displaced population in camps
      provide a basis for under-five mortality surveillance because detailed
      registration databases have been developed. Additionally, health data routinely
      collected on mortality allowed for a review of mortality trends and
      identification of correlating factors to under-five mortality. Literature
      suggests a number of factors that influence child mortality including biological,
      socio-econimic and environmental factors. However, while progress in reducing
      mortality is evident disparities in under-five mortality trends have been
      observed. METHODS: The study examined differential levels and trends of under
      five mortality with correlating factors in Meheba refugee camp in Zambia which is
      presently in its post emergency phase. The retrospective cross-sectional study
      reviewed the ProGres and Health Information System (HIS) databases under-five
      mortality data for a seven (7) year period (2008-2014) and included all children
      aged less than five years in each year of review. STATA 12 (including Ordinary
      Least Squares Regression) and Microsoft Excel 2010 where used for data analysis
      and computation of findings. RESULTS: Malaria and respiratory infections
      accounted for 81 % of under-five deaths while cases of Diarrhoea were responsible
      for 10 % of reported mortalities. Seventy five percent (75 %) of all mortalities
      were reported in children aged less than 1 year (<1 year). While no significant
      variations in mortality were noted as a result of time, increased frequency of
      visits to health centre significantly (P < 0.05) reduced mortalities in children
      by 3/1000 in each year. CONCLUSION: In addition to improving health
      infrastructure and reducing distances to health facilities, the study also
      recommends sensitization programmes targeted at ensuring accessibility to health
      care services for children under-5 years. The study found that increased health
      centre visitations were associated with reduction in under-five mortality and
      encourages initiatives targeted at sensitizing communities to seek health care.
      Furthermore, collaboration between the health systems, community and Non
      Governmental Organisations (NGOs) is key in addressing higher infant mortality
      observed. It is envisaged that this will contribute to the reduction in mortality
      cases and will compliment already existing strategies.

PMID- 27895910
TI  - Proteomic identification of cryostress in epididymal spermatozoa.
AB  - BACKGROUND: Cryopreservation of epididymal spermatozoa is important in cases in
      which it is not possible to collect semen using normal methods, as the sudden
      death of an animal or a catastrophic injury. However, the freezing and thawing
      processes cause stress to spermatozoa, including cold shock, osmotic damage, and
      ice crystal formation, thereby reducing sperm quality. We assessed the motility
      (%), motion kinematics, capacitation status, and viability of spermatozoa using
      computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence
      staining. Moreover, we identified proteins associated with cryostress using a
      proteomic approach and performed western blotting to validate two-dimensional
      electrophoresis (2-DE) results using two commercial antibodies. RESULTS:
      Cryopreservation reduced viability (%), motility (%), straight-line velocity
      (VSL), average path velocity (VAP), amplitude of lateral head displacement (ALH),
      and capacitated spermatozoa, whereas straightness (STR) and the acrosome reaction
      increased after cryopreservation (P < 0.05). Nine proteins were differentially
      expressed (two proteins decreased and seven increased) (>3 fold, P < 0.05) before
      and after cryopreservation. The proteins differentially expressed following
      cryopreservation are putatively related to several signaling pathways, including
      the ephrinR-actin pathway, the ROS metabolism pathway, actin cytoskeleton
      assembly, actin cytoskeleton regulation, and the guanylate cyclase pathway.
      CONCLUSION: The results of the current study provide information on epididymal
      sperm proteome dynamics and possible protein markers of cryo-stress during
      cryopreservation. This information will further the basic understanding of
      cryopreservation and aid future studies aiming to identify the mechanism of
      cryostress responses.

PMID- 27895912
TI  - The measurement of media literacy in eating disorder risk factor research:
      psychometric properties of six measures.
AB  - BACKGROUND: Evaluation of media literacy-based interventions for the prevention
      of eating disorder risk is limited by the lack of appropriate measures with
      established psychometric properties with which to assess change in media
      literacy. This study aims to fill this gap by examining the psychometric
      properties and use in eating disorders risk factor research of six measures of
      media literacy that assess media processing and critical thinking about general
      media and critical thinking about appearance-focused media. METHODS: The factor
      structure, internal consistency, test-retest reliability, and construct validity,
      including convergent and discriminant validity, were examined in six measures in
      two samples of early adolescent females. The measures were the Realism
      Scepticism, Similarity Scepticism, and Desirability Scepticism subscales of the
      Media Attitudes Questionnaire, the Fake subscale of the Critical Processing of
      Beauty Images Scale, the Critical Thinking about Media Messages scale, and
      Critical Thinking about Media Messages - Appearance Focus scale. RESULTS: The
      factor structure of the measures was supported with factor analysis. Items from
      the Media Attitudes Questionnaire loaded on the three subscales Realism
      Scepticism, Similarity Scepticism, and Desirability Scepticism and items from
      each of the Fake subscale, Critical Thinking about Media Messages scale and
      Critical Thinking about Media Messages - Appearance Focus scale loaded on one
      scale. In addition, scores on the measures were reliable (adequate internal
      consistency and test-retest reliability) and valid (adequate construct,
      convergent, and discriminant validity) in early adolescent females. Two
      exceptions were Realism Scepticism, which had slightly low test-retest
      reliability, and the Fake subscale, for which support for construct validity was
      lacking. CONCLUSIONS: This study provides evidence to support the use of select
      media literacy measures, particularly the Realism Scepticism subscale and the
      Critical Thinking about Media Messages scale, in eating disorder risk factor
      research and the findings will contribute to enhanced evaluation of media
      literacy-based prevention interventions.

PMID- 27895913
TI  - Listening in the dark: why we need stories of people living with severe and
      enduring anorexia nervosa.
AB  - A bold step forward in our approach to Severe and Enduring Anorexia Nervosa
      invites new paradigms for research and practice. It provides an opportunity for
      us to explore fault lines, both in our communities of practice and the social
      structures that inform them. This paper serves to question the medical metaphors
      on which treatment has been based, in favour of alternative perspectives that
      resonate more clearly with the lived experience of those for whom it has failed.
      We invite the consideration of alternative metaphors, which can disrupt the
      notion of heroic patients (and therapists), mediate against acts of self
      silencing and sensitising us to more radical acts of listening. Beyond the
      randomised trials and manuals it is time for us to listen to the realities of
      suffering, the minutiae of resistance and the life that can still be lived.

PMID- 27895914
TI  - Revisiting the internal consistency and factorial validity of the 8-item Morisky
      Medication Adherence Scale.
AB  - OBJECTIVE: To assess the internal consistency and factorial validity of the
      adapted French 8-item Morisky Medication Adherence Scale in assessing adherence
      to noninsulin antidiabetic drug treatment. STUDY DESIGN AND SETTING: In a cross
      sectional web survey of individuals with type 2 diabetes of the Canadian province
      of Quebec, self-reported adherence to the antidiabetes drug treatment was
      measured using the Morisky Medication Adherence Scale-8. We assessed the internal
      consistency of the Morisky Medication Adherence Scale-8 with Cronbach's alpha,
      and factorial validity was assessed by identifying the underlying factors using
      exploratory factor analyses. RESULTS: A total of 901 individuals completed the
      survey. Cronbach's alpha was 0.60. Two factors were identified. One factor
      comprised five items: stopping medication when diabetes is under control,
      stopping when feeling worse, feeling hassled about sticking to the prescription,
      reasons other than forgetting and a cross-loading item (i.e. taking drugs the day
      before). The second factor comprised three other items that were all related to
      forgetfulness in addition to the cross-loading item. CONCLUSION: Cronbach's alpha
      of the adapted French Morisky Medication Adherence Scale-8 was below the
      acceptable value of 0.70. This observed low internal consistency of the scale is
      probably related to the causal nature of the items of the scale but not
      necessarily a lack of reliability. The results suggest that the adapted French
      Morisky Medication Adherence Scale-8 is a two-factor scale assessing intentional
      (first factor) and unintentional (second factor) non-adherence to the noninsulin
      antidiabetes drug treatment. The scale could be used to separately identify these
      outcomes using scores obtained on each of the sub-scales.

PMID- 27895915
TI  - Care practices of older people with dementia in the surgical ward: A
      questionnaire survey.
AB  - OBJECTIVES: The objective of this study was to describe the care practices of
      nursing staff caring older people with dementia in a surgical ward. METHODS: The
      data were collected from nursing staff (n = 191) working in surgical wards in one
      district area in Finland during October to November 2015. Data were collected
      using a structured questionnaire and analyzed statistically. The instrument
      consists of a total number of 141 items and four dimensions. The dimensions were
      as follows: background information (12 of items), specific characteristics of
      older people with dementia in a surgical ward (24 of items), specific
      characteristics of their care in a surgical ward (66 of items) and use of
      physical restraints and alternative models for use of restraints for people with
      dementia (39 of items). RESULTS: The questions which measure the nursing staff's
      own assessment of care practices when caring for people with dementia in surgical
      wards were selected: counseling people with dementia, reaction when a surgical
      patient with dementia displays challenging behavior and use of alternative
      approach instead of physical restraints. Most commonly the nursing staff pay
      attention to patient's state of alertness before counseling older people with
      dementia. Instead of using restraints, nursing staff gave painkillers for the
      patient and tried to draw patients' attention elsewhere. The nursing staff with
      longer work experience estimate that they can handle the patients' challenging
      behavior. They react by doing nothing more often than others. They pretend not to
      hear, see or notice anything. CONCLUSION: The findings of this study can be
      applied in nursing practice and in future studies focusing on the care practices
      among older people with dementia in acute care environment. The results can be
      used while developing patient treatments process in surgical ward to meet future
      needs.

PMID- 27895916
TI  - Mechanically produced schistosomula as a higher-throughput tools for phenotypic
      pre-screening in drug sensitivity assays: current research and future trends.
AB  - It is crucial to develop new antischistosomal drugs since there is no vaccine and
      the whole world is relying on only a single drug for the treatment of
      schistosomiasis. One of the obstacles to the development of drugs is the absence
      of the high throughput objective screening methods to assess drug compounds
      efficacy. Thus for identification of new drug compounds candidates, fast and
      accurate in vitro assays are unavoidable and more research efforts in the field
      of drug discovery can target schistosomula. This review presents a substantial
      overview of the present state of in vitro drug sensitivity assays developed so
      far for the determination of anti-schistosomula activity of drug compounds,
      natural products and derivatives using newly transformed schistosomula (NTS). It
      highlights some of the challenges involved in in vitro compound screening using
      NTS and the way forward.

PMID- 27895919
TI  - Recurrent pleural effusions and cardiac tamponade as possible manifestations of
      pseudoprogression associated with nivolumab therapy- a report of two cases.
AB  - BACKGROUND: Checkpoint inhibitors are a class of agents that employ host's
      adaptive immune defenses in fighting cancer. With many new indications and
      several ongoing clinical trials in a variety of malignancies, the usage of these
      agents is set to increase significantly. One of the key challenges patients and
      physicians face while using these drugs is with the appropriate assessment of
      response to therapy. CASE PRESENTATION: We are reporting two patients with lung
      cancer who were treated with nivolumab and experienced rapidly accumulating
      recurrent pleural effusions requiring multiple thoracenteses (6 and 4 times each
      for patient 1 and 2 respectively) with in the first few weeks of initiation of
      therapy and also developed pericardial effusion with cardiac tamponade requiring
      pericardiocentesis. Both patients had prior history of malignant spread to
      pleural and pericardial space in their disease course. Therapy was continued in
      the first patient with spontaneous resolution of effusions after 8 weeks and the
      disease showed near complete response to treatment on imaging at 16 weeks. Second
      patient declined to continue further treatment with nivolumab after 3 cycles due
      to recurrent effusions and cardiac tamponade, although there was some evidence of
      clinical response at discontinuation. CONCLUSIONS: Patients with history of
      malignant involvement of visceral spaces should be monitored closely for rapidly
      accumulating effusions and particularly for cardiac tamponade, after initiation
      of therapy with nivolumab. This presentation could represent pseudoprogression,
      and continuation of therapy with close monitoring is prudent as long as effusions
      are manageable and there is no definitive evidence of progression elsewhere.

PMID- 27895918
TI  - Classical and non-classical HLA class I aberrations in primary cervical squamous-
      and adenocarcinomas and paired lymph node metastases.
AB  - BACKGROUND: Tumors avoid destruction by cytotoxic T cells (CTL) and natural
      killer (NK) cells by downregulation of classical human leukocyte antigens (HLA)
      and overexpression of non-classical HLA. This is the first study to investigate
      HLA expression in relation to histology (squamous cell carcinoma (SCC) vs.
      adenocarcinoma (AC)), clinicopathological parameters and survival in a large
      cervical cancer patient cohort. METHODS: Classical (HLA-A and HLA-B/C)- and non
      classical HLA molecules (HLA-E and HLA-G) were studied on primary tumors and
      paired lymph node (LN) metastases from cervical cancer patients (n = 136) by
      immunohistochemistry. The Chi2 test was used for the comparison of
      clinicopathological characteristics between SCC and AC patients. The Related
      Samples Wilcoxon Signed Rank test was used to compare HLA expression between the
      primary tumor and metastasis in LN. Patient survival rates were analyzed by
      Kaplan-Meier curves and Log Rank test. The Mann-Whitney U Test was used to
      compare the distribution of HLA class I expression between SCC and AC. RESULTS:
      Decreased expression of HLA-A (SCC P < 0.001), HLA-B/C (SCC P < 0.01; AC P <
      0.01) and total classical HLA (SCC P < 0.001; AC P = 0.02) was apparent in
      metastatic tumor cells compared to the primary tumor. In primary SCC, there was a
      clear trend towards complete loss of HLA-A (P = 0.05). SCC metastases showed more
      complete loss of HLA-A, while AC metastases showed more complete loss of HLA-B/C
      (P = 0.04). In addition, tumor size and parametrium involvement were also related
      to aberrant HLA class I expression. No significant associations between HLA
      expression and disease-specific (DSS) or disease-free survival (DFS) were found
      in this advanced disease cohort. However, in the SCC group, samples showing loss
      of HLA-A or loss of total classical HLA but positive for HLA-G were linked to
      poor patient survival (DSS P = 0.001 and P = 0.01; DFS P = 0.003 and P = 0.01,
      for HLA-A and total classical HLA, respectively). CONCLUSION: These results
      strengthen the idea of tumor immune escape variants leading to metastasis.
      Moreover, SCC tumors showing downregulation of HLA-A or total classical HLA in
      combination with HLA-G expression had poor prognosis. Our findings warrant
      further analysis of HLA expression as a biomarker for patient selection for CTL-
      and NK- cell based immunotherapeutic intervention.

PMID- 27895917
TI  - Validation of biomarkers to predict response to immunotherapy in cancer: Volume I
      - pre-analytical and analytical validation.
AB  - Immunotherapies have emerged as one of the most promising approaches to treat
      patients with cancer. Recently, there have been many clinical successes using
      checkpoint receptor blockade, including T cell inhibitory receptors such as
      cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1
      (PD-1). Despite demonstrated successes in a variety of malignancies, responses
      only typically occur in a minority of patients in any given histology.
      Additionally, treatment is associated with inflammatory toxicity and high cost.
      Therefore, determining which patients would derive clinical benefit from
      immunotherapy is a compelling clinical question. Although numerous candidate
      biomarkers have been described, there are currently three FDA-approved assays
      based on PD-1 ligand expression (PD-L1) that have been clinically validated to
      identify patients who are more likely to benefit from a single-agent anti-PD-1/PD
      L1 therapy. Because of the complexity of the immune response and tumor biology,
      it is unlikely that a single biomarker will be sufficient to predict clinical
      outcomes in response to immune-targeted therapy. Rather, the integration of
      multiple tumor and immune response parameters, such as protein expression,
      genomics, and transcriptomics, may be necessary for accurate prediction of
      clinical benefit. Before a candidate biomarker and/or new technology can be used
      in a clinical setting, several steps are necessary to demonstrate its clinical
      validity. Although regulatory guidelines provide general roadmaps for the
      validation process, their applicability to biomarkers in the cancer immunotherapy
      field is somewhat limited. Thus, Working Group 1 (WG1) of the Society for
      Immunotherapy of Cancer (SITC) Immune Biomarkers Task Force convened to address
      this need. In this two volume series, we discuss pre-analytical and analytical
      (Volume I) as well as clinical and regulatory (Volume II) aspects of the
      validation process as applied to predictive biomarkers for cancer immunotherapy.
      To illustrate the requirements for validation, we discuss examples of biomarker
      assays that have shown preliminary evidence of an association with clinical
      benefit from immunotherapeutic interventions. The scope includes only those
      assays and technologies that have established a certain level of validation for
      clinical use (fit-for-purpose). Recommendations to meet challenges and strategies
      to guide the choice of analytical and clinical validation design for specific
      assays are also provided.

PMID- 27895922
TI  - Commentary to Nicastro et al. (2016), Borderline Personality Disorder and Emotion
      Dysregulation.

PMID- 27895920
TI  - PD1/PD-L1 inhibition as a potential radiosensitizer in head and neck squamous
      cell carcinoma: a case report.
AB  - BACKGROUND: Immunotherapy targeting the checkpoint PD1 (programmed cell death
      protein 1) or PDL1 (programmed death ligand 1) has led to advances in the
      treatment of melanoma and non-small cell lung cancer (NSCLC). The use of such
      therapies has also been introduced into the treatment of other malignancies,
      including head and neck cancer. The combined effects of checkpoint inhibitors and
      anti-PD1(L1) antibodies and radiation therapy have not yet been sufficiently
      investigated. CASE PRESENTATION: We report a case of locally relapsed non
      resectable oral cavity squamous cell carcinoma, with excellent local control
      after pembrolizumab (MK3475) followed by radiotherapy. CONCLUSION: T cell
      activation induced by checkpoint inhibition may dramatically improve tumor
      response to radiation. More data are needed to identify the toxicity and efficacy
      of sequential or concurrent checkpoint inhibitors and radiotherapy.

PMID- 27895921
TI  - Literature review of vaccine-related adverse events reported from HPV vaccination
      in randomized controlled trials.
AB  - BACKGROUND: The human papilloma virus (HPV) infections were addressed with two
      FDA-approved HPV vaccines: quadrivalent and bivalent vaccine. The objective of
      this manuscript is to determine the safety of the HPV vaccine. RESULTS: A search
      of PubMed articles for "human papillomavirus vaccine" was used to identify all
      type HPV clinical studies prior to October 2014. A refined search of clinical
      trials, multicenter studies, and randomized studies were screened for only
      randomized controlled trials comparing HPV vaccine to controls (saline placebo or
      aluminum derivatives). Studies were limited to the two FDA-approved vaccines.
      Following PRISMA guidelines, the literature review rendered 13 publications that
      met inclusion/ exclusion criteria. Gender was limited to females in 10 studies
      and males in 1 study. Two studies included both males and females. Of the 11,189
      individuals in 7 publications reporting cumulative, all-type adverse events (AE),
      the AE incidence of 76.52 % (n = 4544) in the vaccinated group was statistically
      significantly higher than 67.57 % (n = 3548) in the control group (p < 0.001).
      The most common AE were injection-site reactions. On the other hand, systemic
      symptoms did not statistically significantly differ between the vaccination
      cohort (35.28 %, n = 3351) and the control cohort (36.14 %, n = 3198) (p =
      0.223). The pregnancy/ perinatal outcomes rendered no statistically significant
      difference between the vaccine group and control group. CONCLUSION: Because the
      statistically significantly higher incidence of AE in the HPV vaccine group was
      primarily limited to injection-site reactions, the vaccinations are safe
      preventative measures in both males and females.

PMID- 27895923
TI  - Concurrent validity of the Gyko inertial sensor system for the assessment of
      vertical jump height in female sub-elite youth soccer players.
AB  - BACKGROUND: The aim of the present study was to verify concurrent validity of the
      Gyko inertial sensor system for the assessment of vertical jump height. METHODS:
      Nineteen female sub-elite youth soccer players (mean age: 14.7 +/- 0.6 years)
      performed three trials of countermovement (CMJ) and squat jumps (SJ),
      respectively. Maximal vertical jump height was simultaneously quantified with the
      Gyko system, a Kistler force-plate (i.e., gold standard), and another criterion
      device that is frequently used in the field, the Optojump system. RESULTS:
      Compared to the force-plate, the Gyko system determined significant systematic
      bias for mean CMJ (-0.66 cm, p < 0.01, d = 1.41) and mean SJ (-0.91 cm, p < 0.01,
      d = 1.69) height. Random bias was +/- 3.2 cm for CMJ and +/- 4.0 cm for SJ height
      and intraclass correlation coefficients (ICCs) were "excellent" (ICC = 0.87 for
      CMJ and 0.81 for SJ). Compared to the Optojump device, the Gyko system detected a
      significant systematic bias for mean CMJ (0.55 cm, p < 0.05, d = 0.94) but not
      for mean SJ (0.39 cm) height. Random bias was +/- 3.3 cm for CMJ and +/- 4.2 cm
      for SJ height and ICC values were "excellent" (ICC = 0.86 for CMJ and 0.82 for
      SJ). CONCLUSION: Consequently, apparatus specific regression equations were
      provided to estimate true vertical jump height for the Kistler force-plate and
      the Optojump device from Gyko-derived data. Our findings indicate that the Gyko
      system cannot be used interchangeably with a Kistler force-plate and the Optojump
      device in trained individuals. It is suggested that practitioners apply the
      correction equations to estimate vertical jump height for the force-plate and the
      Optojump system from Gyko-derived data.

PMID- 27895925
TI  - Somatic neural alterations in non-diabetic obesity: a cross-sectional study.
AB  - BACKGROUND: Reports on alterations in somatic neural functions due to non
      diabetic obesity, a major risk factor for diabetes, are few and still a matter of
      debate. Nevertheless, to our knowledge, reports lack any comments on the type of
      somatic nerve fibers affected in non-diabetic obesity. Therefore, this study
      aimed to find out the alteration in somatic neural functions in non-diabetic
      obese persons if any. METHODS: The study was conducted on 30 adult non-diabetic
      obese persons (mean age 32.07 +/- 7.25 years) with BMI > 30 Kg/m2 (mean BMI 30.02
      +/- 2.89 Kg/m2) and 29 age- and sex-matched normal weight controls (mean age
      30.48 +/- 8.01 years) with BMI: 18-24Kg/m2 (mean BMI 21.87 +/- 2.40 Kg/m2). Nerve
      conduction study (NCS) variables of median, tibial and sural nerves were assessed
      in each subject using standard protocol. The data were compared by Mann Whitney
      'U' test. RESULTS: In comparison to normal weight persons, obese had lower
      compound muscle action potential (CMAP) amplitudes of right median [9.09(7.62
      10.20) Vs 10.75(8.71-12.2) mV, p = 0.025] and bilateral tibial nerves [Right:
      8.5(7.04-11.18) Vs 12.1(10.55-15) mV, p < 0.001 and left 9.08(6.58-11.65) Vs
      13.05(10.2-15.6) mV, p = 0.002]. Furthermore, obese persons had prolonged CMAP
      durations of right and left median [10.5(9.62-12) Vs 10(8.4-10.3) ms, p = 0.02
      and 10.85(10-11.88) Vs 10(9-10.57) ms, p = 0.019] and right tibial [10(9-11)
      8.5(7.92-10) ms, p = 0.032] nerves. Sensory NCS (sural nerve) also showed
      diminished sensory nerve action potential (SNAP) amplitude [16(12.08-18.21) vs
      22.8(18.3-31.08) MUV, p < 0.001] and prolonged duration. However, onset latencies
      and conduction velocities for all nerves were comparable between the groups.
      CONCLUSION: This study documents subclinical peripheral nerve damage in non
      diabetic obese with abnormal NCS parameters; shorter amplitudes and prolonged
      CMAP and SNAP durations. The reduced amplitudes of mixed and sensory nerves might
      be due to decreased axonal number stimulation or actual decrease in number of
      axonal fibers, or defect at NMJ in non-diabetic obese. Prolonged durations but
      normal onset latencies and conduction velocities strongly suggest involvement of
      slow conducting fibers.

PMID- 27895924
TI  - Urinary arsenic species concentration in residents living near abandoned metal
      mines in South Korea.
AB  - BACKGROUND: Arsenic is a carcinogenic heavy metal that has a species-dependent
      health effects and abandoned metal mines are a source of significant arsenic
      exposure. Therefore, the aims of this study were to analyze urinary arsenic
      species and their concentration in residents living near abandoned metal mines
      and to monitor the environmental health effects of abandoned metal mines in
      Korea. METHODS: This study was performed in 2014 to assess urinary arsenic
      excretion patterns of residents living near abandoned metal mines in South Korea.
      Demographic data such as gender, age, mine working history, period of residency,
      dietary patterns, smoking and alcohol use, and type of potable water consumed
      were obtaining using a questionnaire. Informed consent was also obtained from all
      study subjects (n = 119). Urinary arsenic species were quantified using high
      performance liquid chromatography (HPLC) and inductively coupled plasma mass
      spectrometry (ICP/MS). RESULTS: The geometric mean of urinary arsenic (sum of
      dimethylarsinic acid, monomethylarsonic acid, As3+, and As5+) concentration was
      determined to be 131.98 MUg/L (geometric mean; 95% CI, 116.72-149.23) while
      urinary inorganic arsenic (As3+ and As5+) concentration was 0.81 MUg/L (95% CI,
      0.53-1.23). 66.3% (n = 79) and 21.8% (n = 26) of these samples exceeded ATSDR
      reference values for urinary arsenic (>100 MUg/L) and inorganic arsenic (>10
      MUg/L), respectively. Mean urinary arsenic concentrations (geometric mean, GM)
      were higher in women then in men, and increased with age. Of the five regions
      evaluated, while four regions had inorganic arsenic concentrations less than 0.40
      MUg/L, one region showed a significantly higher concentration (GM 15.48 MUg/L;
      95% CI, 7.51-31.91) which investigates further studies to identify etiological
      factors. CONCLUSION: We propose that the observed elevation in urinary arsenic
      concentration in residents living near abandoned metal mines may be due to
      environmental contamination from the abandoned metal mine. TRIAL REGISTRATION:
      Not Applicable (We do not have health care intervention on human participants).

PMID- 27895926
TI  - Non-invasive brain stimulation as a tool to study cerebellar-M1 interactions in
      humans.
AB  - The recent development of non-invasive brain stimulation techniques such as
      transcranial magnetic stimulation (TMS) has allowed the non-invasive assessment
      of cerebellar function in humans. Early studies showed that cerebellar activity,
      as reflected in the excitability of the dentate-thalamo-cortical pathway, can be
      assessed with paired stimulation of the cerebellum and the primary motor cortex
      (M1) (cerebellar inhibition of motor cortex, CBI). Following this, many attempts
      have been made, using techniques such as repetitive TMS and transcranial
      electrical stimulation (TES), to modulate the activity of the cerebellum and the
      dentate-thalamo-cortical output, and measure their impact on M1 activity. The
      present article reviews literature concerned with the impact of non-invasive
      stimulation of cerebellum on M1 measures of excitability and "plasticity" in both
      healthy and clinical populations. The main conclusion from the 27 reviewed
      articles is that the effects of cerebellar "plasticity" protocols on M1 activity
      are generally inconsistent. Nevertheless, two measurements showed relatively
      reproducible effects in healthy individuals: reduced response of M1 to
      sensorimotor "plasticity" (paired-associative stimulation, PAS) and reduced CBI
      following repetitive TMS and TES. We discuss current challenges, such as the low
      power of reviewed studies, variability in stimulation parameters employed and
      lack of understanding of physiological mechanisms underlying CBI.

PMID- 27895927
TI  - Expansion, mosaicism and interruption: mechanisms of the CAG repeat mutation in
      spinocerebellar ataxia type 1.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative
      disorder that primarily affects the cerebellum and brainstem. The genetic
      mutation is an expansion of CAG trinucleotide repeats within the coding region of
      the ataxin-1 gene, characterizing SCA1 as a polyglutamine expansion disease like
      Huntington's. As with most polyglutamine expansion diseases, SCA1 follows the
      rules of genetic anticipation: the larger the expansion, the earlier and more
      rapid the symptoms. Unlike the majority of polyglutamine expansion diseases, the
      presence of histidine interruptions within the polyglutamine tract of ataxin-1
      protein can prevent or mitigate disease. The present review aims to synthesize
      three decades of research on the ataxin-1 polyglutamine expansion mutation that
      causes SCA1. Data from genetic population studies and case studies is gathered
      along with data from manipulation studies in animal models. Specifically, we
      examine the molecular mechanisms that cause tract expansions and contractions,
      the molecular pathways that confer instability of tract length in gametic and
      somatic cells resulting in gametic and somatic mosaicism, the influence of
      maternal or paternal factors in inheritance of the expanded allele, and the
      effects of CAT/histidine interruptions to the ataxin-1 allele and protein
      product. Our review of existing data supports the following conclusions. First,
      polyCAG expansion of gametic alleles occur due to the failure of gap repair
      mechanisms for single or double strand breaks during the transition from an
      immature haploid spermatid to a mature haploid sperm cell. Equivalent failures
      were not detected in female gametic cells. Second, polyCAG expansion of somatic
      alleles occur due to hairpins formed on Okazaki fragments and slipped strand
      structures due to failures in mismatch repair and transcription-coupled
      nucleotide excision repair mechanisms. Third, CAT trinucleotide interruptions,
      which code for histidines in the translated protein, attenuate the formation of
      slipped strand structures which may protect the allele from the occurrence of
      large expansions. Many of the mechanisms of expansion identified in this review
      differ from those noted in Huntington's disease indicating that gene -or sequence
      specific factors may affect the behavior of the polyCAG/glutamine tract.
      Therefore, synthesis and review of research from the SCA1 field is valuable for
      future clinical and diagnostic work in the treatment and prevention of SCA1.

PMID- 27895929
TI  - Late complications of bariatric surgery in pregnancy.
AB  - Severe complications of bariatric surgery in pregnancy can appear many years
      later, even if there is a history of an uneventful pregnancy after bariatric
      surgery and a stable body mass index for years. We present the case of a pregnant
      patient who presented to our gynaecology department with an internal herniation
      after Roux and Y gastric bypass surgery.

PMID- 27895928
TI  - Assessing the population impact of low rates of vitamin D supplementation on type
      1 diabetes using a new statistical method.
AB  - Vitamin D supplementation for all children <5 is recommended by the UK Department
      of Health for its skeletal effects. Vitamin D is also linked with a number of
      extra-skeletal effects; one of them being protection against type 1 diabetes.
      With a rapid increase in the incidence of type 1 diabetes and the associated
      costs, measures of curtailing the rapid increase of type 1 diabetes are needed.
      In this review, we look at type 1 diabetes using a statistical method (PIN-ER-t)
      and published data in an attempt to quantify the impact on the population of
      babies born in 2012 of increasing vitamin D supplementation rates. Calculations
      show that for the population of 729,674 babies born in England and Wales in 2012,
      374 cases of type 1 diabetes (out of 1357 total predicted) could be prevented
      over 18 years if all were supplemented with vitamin D. This could lead to savings
      in excess of L62 million for the cohort. This piece of work adds to the argument
      for studying the potential link between vitamin D supplementation and type 1
      diabetes further.

PMID- 27895930
TI  - Obstetric patients in intensive care unit: Perspective from a teaching hospital
      in Pakistan.
AB  - OBJECTIVE: Review of obstetric cases admitted to the intensive care unit. DESIGN:
      Ten year retrospective review of individual patients' medical records.
      PARTICIPANTS: Records of obstetric patients admitted from 2005-2014. SETTING: Aga
      Khan University Hospital Karachi. MAIN OUTCOME MEASURES: Diagnosis at the time of
      admission, associated risk factors, and intervention required aspects of
      management and rate of mortality. FINDINGS: A total of 194 obstetric patients
      were admitted out of which 86.2% of patients had ventilator support. Mortality
      was not seen to be significantly associated with parity and antenatal/postnatal
      status. The median age of patients was 34 years, minimum length of stay was 24
      hours and maximum stay was 53 days. Sixty one percent of patients were admitted
      to with organ system failure. The overall mortality rate was 21.64% (42/194). The
      mortality rate was five times more likely in patients who had gastro-intestinal
      complication {Odds Ratio=4.87; 95%CI: 1.65-14.36}. The largest group of patients
      {28.4%} presented with hematological diagnosis. CONCLUSION: When the intensive
      care unit admission became essential, primary diagnosis included: postpartum
      hemorrhage, hypertensive disorders, sepsis and infectious diseases. An increased
      vigilance of high-risk pregnant women and a stabilization of their condition
      before intervention is administered, improves the outcome of these women.

PMID- 27895931
TI  - Erratum: Publisher's Erratum: Spinal-generated movement disorders: a clinical
      review.
AB  - [This corrects the article DOI: 10.1186/s40734-015-0028-1.].

PMID- 27895933
TI  - Influence of proton pump inhibitors and histamine H2 receptor antagonists on
      serum phosphorus level control by calcium carbonate in patients undergoing
      hemodialysis: a retrospective medical chart review.
AB  - BACKGROUND: Hyperphosphatemia is one of the common complications in patients
      undergoing hemodialysis. Although calcium carbonate (CaC) is often used to
      control serum inorganic phosphorus level in dialysis patients, co-administration
      of gastric acid reducers (ARs) may interfere with the phosphate binding effect of
      CaC. We performed a retrospective medical chart review to study whether ARs
      attenuate the hypophosphatemic effect of CaC in patients undergoing hemodialysis.
      METHODS: One hundred and eight chronic hemodialysis patients receiving either CaC
      alone or CaC concomitant with one of the ARs (proton pump inhibitors and
      histamine H2-receptor antagonists) were retrieved from the medical charts in
      Juntendo University Nerima Hospital. The patients were subdivided according to
      the interval between hemodialysis sessions (interdialysis interval of 48 or 72
      h). A multivariate analysis was performed to identify clinical covariates
      associated with the variability of serum inorganic phosphorus levels. The study
      protocol was approved by the Institutional Review Board before the study was
      begun. RESULTS: Among patients on hemodialysis with a 72-h interdialysis
      interval, the magnitude of increase in serum inorganic phosphorus concentration
      in patients receiving CaC and AR was significantly greater than in those
      receiving CaC alone. While a similar trend was observed among patients with a 48
      h interdialysis interval, the difference did not reach a significant level. A
      multivariate regression analysis revealed that concomitant administration of ARs
      with CaC and a longer interdialysis interval (72 h) were significantly and
      independently associated with the magnitude of increase in serum phosphorus
      concentration between dialysis sessions. No significant differences in albumin
      corrected serum calcium concentrations and incidence of pathological fractures
      were observed between patients receiving CaC alone and those receiving CaC with
      ARs. CONCLUSIONS: Concomitant use of ARs with CaC may attenuate the
      hypophosphatemic effect of CaC in patients undergoing chronic hemodialysis. When
      hemodialysis patients require prescription of ARs for the prevention of upper
      gastrointestinal mucosal diseases (such as peptic ulcer), it may be prudent to
      choose a phosphate binder other than CaC.

PMID- 27895934
TI  - Liposomal delivery systems for intestinal lymphatic drug transport.
AB  - Intestinal lymphatic drug delivery has been widely studied because drugs can
      bypass the first-pass metabolism in the liver via the lymphatic route, which
      increases oral bioavailability. Various lipid-based nanoparticles have been used
      to deliver hydrophobic drugs to the lymphatic pathway. This review focuses on the
      liposomal delivery systems used for intestinal lymphatic drug transport.
      Liposomal formulations have attracted particular attention because they can
      stimulate the production of chylomicrons and the incorporated drugs readily
      associate with enterocyte-derived chylomicrons, enhancing lymphatic drug
      transport. We believe that a full understanding of their contribution to
      intestinal drug translocation will lead to effective oral delivery with liposomal
      formulations.

PMID- 27895932
TI  - Coagulation complications following trauma.
AB  - Traumatic injury is one of the leading causes of death, with uncontrolled
      hemorrhage from coagulation dysfunction as one of the main potentially
      preventable causes of the mortality. Hypothermia, acidosis, and resuscitative
      hemodilution have been considered as the significant contributors to coagulation
      manifestations following trauma, known as the lethal triad. Over the past decade,
      clinical observations showed that coagulopathy may be present as early as
      hospital admission in some severely injured trauma patients. The hemostatic
      dysfunction is associated with higher blood transfusion requirements, longer
      hospital stay, and higher mortality. The recognition of this early coagulopathy
      has initiated tremendous interest and effort in the trauma community to expand
      our understanding of the underlying pathophysiology and improve clinical
      treatments. This review discusses the current knowledge of coagulation
      complications following trauma.

PMID- 27895935
TI  - Systolic blood pressure values might further risk-stratify the adverse outcomes
      of LVH in older patients with chronic kidney disease.
AB  - BACKGROUND: LVH is highly prevalent in patients with CKD and is independently
      associated with subsequent cardiovascular events. We hypothesized that adding
      systolic blood pressure values to LVH might differentiate different subgroups of
      patients at higher risk of cardiovascular events (CVE) and other adverse
      outcomes. METHODS: Retrospective cohort study of 243 patients older than 60 years
      with stages 1-5 pre-dialysis CKD. LVH was assessed by electrocardiogram or
      echocardiogram. RESULTS: Cardiovascular events occurred in 7 patients (10.3%)
      among those with SBP <130 and no LVH, 8 patients (10.5%) among those with SBP
      >=130 and no LVH, 7 patients (21.2%) among those with SBP <130 and LVH and 25
      patients (37.9%) among those with SBP >= 130 and LVH. On multivariate analyses,
      comparing to SBP < 130 and no LVH, the HR for CVE in those with SBP >= 130 and
      LVH was 4 (1.75, 10.3), p = 0.0007; 2.13 (0.71, 6.32) p = 0.16 in those with SBP
      <130 and LVH and 1.20 (0.42, 3.51) p = 0.72 in those with SBP >=130 and no LVH.
      No significant differences were noted in changes in renal function and mortality
      rates among the groups. CONCLUSION: The combination of higher systolic blood
      pressure and LVH might identify older patients with CKD at higher risk of
      cardiovascular outcomes.

PMID- 27895938
TI  - Understanding colonization and proliferation potential of endophytes and pathogen
      in planta via plating, polymerase chain reaction and ergosterol assay.
AB  - This study aimed to establish the colonization behavior and proliferation
      potential of three endophytes and one pathogen Ganoderma boninense (Gb)
      introduced into oil palm ramets (host model). The endophytes selected were
      Diaporthe phaseolorum (WAA02), Trichoderma asperellum (T2), and Penicillium
      citrinum (BTF08). Ramets were first inoculated with 100 mL of fungal cells (106
      cfu mL-1) via soil drenching. For the next 7 days, ramets were sampled and
      subjected to three different assays to detect and identify fungal colonization,
      and establish their proliferation potential in planta. Plate assay revealed the
      presence of endophytes in root, stem and leaf tissues within 7 days after
      inoculation. Polymerase Chain Reaction (PCR) detected and identified the isolates
      from the plant tissues. The ergosterol assay (via high performance liquid
      chromatography, HPLC) confirmed the presence of endophytes and Gb in planta. The
      increase in ergosterol levels throughout 49 days was however insignificant,
      suggesting that proliferation may be absent or may occur very slowly in planta.
      This study strongly suggests that the selected endophytes could colonize the host
      upon inoculation, but proliferation occurs at a slower rate, which may
      subsequently influence the biocontrol expression of endophytes against the
      pathogen.

PMID- 27895936
TI  - Neovascular glaucoma: a review.
AB  - Neovascular glaucoma (NVG) is a secondary glaucoma generally associated with poor
      visual prognosis. The development of new vessels over the iris and the
      iridocorneal angle can obstruct aqueous humor outflow and lead to increased
      intraocular pressure. The underlying pathogenesis in most cases is posterior
      segment ischemia, which is most commonly secondary to proliferative diabetic
      retinopathy or central vein retinal occlusion. The neovascularization process in
      the eye is driven by the events that alter the homeostatic balance between pro
      angiogenic factors, such as the vascular endothelial growth factor and anti
      angiogenic factors, such as the pigment-epithelium-derived factor. Early
      diagnosis of this condition through slit lamp examination of the iris,
      iridocorneal angle and retina can help to avoid the development of goniosynechia
      and obstruction of aqueous humor outflow, with consequent intraocular pressure
      elevation. Historically, NVG treatment was focused on reducing the posterior
      segment ischemic process that caused the formation of new vessels, through
      panretinal photocoagulation. Recently, several studies have investigated the
      application of intravitreal anti-VEGF therapies in NVG. If clinical treatment
      with the use of hypotensive topical drops is not sufficient, laser and/or
      surgical procedures are required for intraocular pressure control.

PMID- 27895939
TI  - Malaria, Moderate to Severe Anaemia, and Malarial Anaemia in Children at
      Presentation to Hospital in the Mount Cameroon Area: A Cross-Sectional Study.
AB  - Background. Malaria remains a major killer of children in Sub-Saharan Africa,
      while anaemia is a public health problem with significant morbidity and
      mortality. Examining the factors associated with moderate to severe anaemia
      (MdSA) and malarial anaemia as well as the haematological characteristics is
      essential. Methodology. Children (1-14 years) at presentation at the Regional
      Hospital Annex-Buea were examined clinically and blood samples were collected for
      malaria parasite detection and full blood count evaluation. Results. Plasmodium
      falciparum, anaemia, and malarial anaemia occurred in 33.8%, 62.0%, and 23.6% of
      the 216 children, respectively. Anaemia prevalence was significantly higher in
      malaria parasite positive children and those with fever than their respective
      counterparts. MdSA and moderate to severe malarial anaemia (MdSMA) were detected
      in 38.0% and 15.3% of the participants, respectively. The prevalence of MdSA was
      significantly higher in children whose household head had no formal education,
      resided in the lowland, or was febrile, while MdSMA was significantly higher in
      febrile children only. Children with MdSMA had significantly lower mean white
      blood cell, lymphocyte, and platelet counts while the mean granulocyte count was
      significantly higher. Conclusion. Being febrile was the only predictor of both
      MdSA and MdSMA. More haematological insult occurred in children with MdSMA
      compared to MdSA.

PMID- 27895940
TI  - Real-Time Reporting of Small Operational Failures in Nursing Care.
AB  - Addressing microsystem problems from the frontline holds promise for quality
      enhancement. Frontline providers are urged to apply quality improvement; yet no
      systematic approach to problem detection has been tested. This study investigated
      a self-report approach to detecting operational failures encountered during
      patient care. Methods. Data were collected from 5 medical-surgical units over 4
      weeks. Unit staff documented operational failures on a small distinctive Pocket
      Card. Frequency distributions for the operational failures in each category were
      calculated for each hospital overall and disaggregated by shift. Rate of
      operational failures on each unit was also calculated. Results. A total of 160
      nurses participated in this study reporting a total of 2,391 operational failures
      over 429 shifts. Mean number of problems per shift varied from 4.0 to 8.5
      problems with equipment/supply problems being the most commonly reported
      category. Conclusions. Operational failures are common on medical-surgical
      clinical units. It is feasible for unit staff to record these failures in real
      time. Many types of failures were recognized by frontline staff. This study
      provides preliminary evidence that the Pocket Card is a feasible approach to
      detecting operational failures in real time. Continued research on methodologies
      to investigate the impact of operational failures is warranted.

PMID- 27895942
TI  - An Unusual Lacerated Tracheal Tube during Le Fort Surgery: Literature Review and
      Case Report.
AB  - Maxillofacial surgeries can present unique anesthetic challenges due to
      potentially complex anatomy and the close proximity of the patient's airway to
      the surgical field. Damage to the tracheal tube (TT) during maxillofacial surgery
      may lead to significant airway compromise. We report the management of a patient
      with a partially severed TT during Le Fort surgery for midfacial hypoplasia and
      management strategies based on peer-reviewed literature. This case illustrates
      the clinical clues associated with a damaged TT and explores the challenges of
      managing this potentially catastrophic issue.

PMID- 27895941
TI  - Midbrain Frequency Representation following Moderately Intense Neonatal Sound
      Exposure in a Precocious Animal Model (Chinchilla laniger).
AB  - Auditory brain areas undergo reorganization resulting from abnormal sensory input
      during early postnatal development. This is evident from studies at the cortical
      level but it remains unclear whether there is reorganization in the auditory
      midbrain in a species similar to the human, that is, with early hearing onset. We
      have explored midbrain plasticity in the chinchilla, a precocious species that
      matches the human in terms of hearing development. Neonatal chinchillas were
      chronically exposed to a 2 kHz narrowband sound at 70 dB SPL for 4 weeks.
      Tonotopic maps in inferior colliculus (central nucleus) were defined based on
      single neuron characteristic frequency. We hypothesized an overrepresentation of
      the 2 kHz region of the maps. However, we observed a significant decrease in the
      proportion of neurons dedicated to the 2 kHz octave band and also away from the
      exposure frequency at 8 kHz. In addition, we report a significant increase in low
      frequency representation (<1 kHz), again a change to tonotopic mapping distant to
      the 2 kHz region. Thus in a precocious species, tonotopic maps in auditory
      midbrain are altered following abnormal stimulation during development. However,
      these changes are more complex than the overrepresentation of exposure related
      frequency regions that are often reported.

PMID- 27895937
TI  - Medical Management of Glaucoma in the 21st Century from a Canadian Perspective.
AB  - Glaucoma is a medical term describing a group of progressive optic neuropathies
      characterized by degeneration of retinal ganglion cells and retinal nerve fibre
      layer and resulting in changes in the optic nerve head. Glaucoma is a leading
      cause of irreversible vision loss worldwide. With the aging population it is
      expected that the prevalence of glaucoma will continue to increase. Despite
      recent advances in imaging and visual field testing techniques that allow
      establishment of earlier diagnosis and treatment initiation, significant numbers
      of glaucoma patients are undiagnosed and present late in the course of their
      disease. This can lead to irreversible vision loss, reduced quality of life, and
      a higher socioeconomic burden. Selection of therapeutic approaches for glaucoma
      should be based on careful ocular examination, patient medical history, presence
      of comorbidities, and awareness of concomitant systemic therapies. Therapy should
      also be individualized to patients' needs and preferences. Recent developments in
      this therapeutic field require revisiting treatment algorithms and integration of
      traditional and novel approaches in order to ensure optimal visual outcomes. This
      article provides an overview of recent developments and practice trends in the
      medical management of glaucoma in Canada. A discussion of the surgical management
      is beyond the scope of this paper.

PMID- 27895943
TI  - Congenital Unilateral Agenesis of the Parotid Gland: A Case Report and Review of
      the Literature.
AB  - Congenital unilateral agenesis of the parotid gland is a rare condition with only
      few cases reported in the literature. A review of 21 cases in the available
      literature is presented in this article. We report on a further case of a 34-year
      old woman with agenesis of the left parotid gland and lipoma of the right cheek.
      Clinicopathological characteristics of described cases in the literature were
      discussed.

PMID- 27895944
TI  - Effects of Cryolipolysis on Abdominal Adiposity.
AB  - Cryolipolysis is a noninvasive technique of localized fat reduction. Controlled
      cold exposure is performed in the selective destruction of fat cells. The aim of
      this study was to investigate the effects of cryolipolysis on adipocytes
      elimination through histological and sonographic analyses. This study reports the
      case of a 46-year-old female patient, with complaint of localized abdominal fat
      and in the preoperative period of abdominoplasty. The patient was submitted to a
      single 60-minute application of cryolipolysis, temperature of -5 degrees C, on
      the hypogastrium area, 5 cm below the umbilicus. To study the effects of this
      treatment, ultrasound images taken before the session and 7, 15, 30, and 45 days
      after the therapy were analysed. After the abdominoplasty, parts of the treated
      and the untreated withdrawn abdominal tissues were evaluated macro- and
      microscopically. In ultrasound images, as well as in macroscopic and histological
      analyses, significant adipocytes destruction was detected, with consequent fat
      layer reduction and integrity of areas that were adjacent to the treated tissue.
      The presence of fibrosis observed during therapy and acknowledged through
      performed analyses encourages further studies to clarify such finding.

PMID- 27895945
TI  - Congenital Renal Fusion and Ectopia in the Trauma Patient.
AB  - We present two separate cases of young male patients with congenital kidney
      anomalies (horseshoe and crossed fused renal ectopia) identified following blunt
      abdominal trauma. Despite being rare, ectopic and fusion anomalies of the kidneys
      are occasionally noted in a trauma patient during imaging or upon exploration of
      the abdomen. Incidental renal findings may influence the management of traumatic
      injuries to preserve and protect the patient's renal function. Renal anomalies
      may be asymptomatic or present with hematuria, flank or abdominal pain,
      hypotension, or shock, even following minor blunt trauma or low velocity impact.
      It is important for the trauma clinician to recognize that this group of
      congenital anomalies may contribute to unusual symptoms such as gross hematuria
      after minor trauma, are readily identifiable during CT imaging, and may affect
      operative management. These patients should be informed of their anatomical
      findings and encouraged to return for long-term follow-up.

PMID- 27895947
TI  - Subacute Bacterial Endocarditis with Leptotrichia goodfellowii in a Patient with
      a Valvular Allograft: A Case Report and Review of the Literature.
AB  - Leptotrichia species are normal constituents of the oral cavity and the
      genitourinary tract microbiota that are known to provoke disease in
      immunocompromised patients and rarely in immunocompetent individuals. Following
      the description of Leptotrichia goodfellowii sp. nov., two cases of endocarditis
      by this species have been reported. Here, we report a case of Leptotrichia
      goodfellowii endocarditis in an immunocompetent patient with a valvular
      allograft. The isolation and identification of Leptotrichia can be challenging,
      and it is likely that infection with this pathogen is significantly
      underdiagnosed. A definitive identification, as in this case, most often requires
      16S rRNA gene sequencing, highlighting the increasingly important role of this
      diagnostic modality among immunocompetent patients with undetermined anaerobic
      bacteremia.

PMID- 27895946
TI  - A Case of False-Positive Mycobacterium tuberculosis Caused by Mycobacterium
      celatum.
AB  - Mycobacterium celatum is a nontuberculous mycobacterium shown to cause symptoms
      similar to pulmonary M. tuberculosis. Certain strains have been shown to cross
      react with the probes used to detect M. tuberculosis, making this a diagnostic
      challenge. We present a 56-year-old gentleman who developed signs and symptoms of
      lung infection with computed tomography scan of the chest showing right lung apex
      cavitation. Serial sputum samples were positive for acid-fast bacilli and nucleic
      acid amplification testing identified M. tuberculosis ribosomal RNA, resulting in
      treatment initiation. Further testing with high performance liquid chromatography
      showed a pattern consistent with M. celatum. This case illustrates the potential
      for M. celatum to mimic M. tuberculosis in both its clinical history and
      laboratory testing due to the identical oligonucleotide sequence contained in
      both. An increasing number of case reports suggest that early reliable
      differentiation could reduce unnecessary treatment and public health intervention
      associated with misdiagnosed tuberculosis.

PMID- 27895948
TI  - Pediatric Balint's Syndrome Variant: A Possible Diagnosis in Children.
AB  - Balint's syndrome is well described in adults, but not in children. It is caused
      by bilateral posterior parietal lobe damage and comprises a triad of
      simultanagnosia (inability to simultaneously see more than a small number of
      items), optic ataxia (impaired visual guidance of movement of the limbs and
      body), and apraxia of gaze (inability to volitionally direct gaze despite the
      requisite motor substrate) often associated with homonymous lower visual field
      loss. We, here, describe five children (four males, one female; mean age 7.4
      years, [range 4-11 years]; birth weight <= 2.5 kg; four were born <= 36 weeks of
      gestational age and one at 40 weeks) who presented to the Cerebral Visual
      Impairment Clinic at a tertiary care center in South India with clinical features
      remarkably consistent with the above description. In all children neuroimaging
      showed bilateral parietooccipital gliosis with regional white matter volume loss
      and focal callosal thinning, consistent with perinatal hypoxic ischemic
      encephalopathy and possible neonatal hypoglycemia.

PMID- 27895949
TI  - Primary Ewing's Sarcoma of the Spine in a Two-Year-Old Boy.
AB  - Ewing's Sarcoma (ES) is a highly malignant bone tumour. It may involve any part
      of the skeleton but the most frequent parts are the ilium and diaphysis of femur
      and tibia (Alfeeli et al., 2005; Zhu et al., 2012). Primary ES of the spine is
      extremely rare (Yan et al., 2011). It accounts for only 3.5 to 14.9 percent of
      all primary bone sarcomas. The age of presentation ranges from 12 to 24 years
      (median 21 years) (Ferguson, 1999; Sharafuddin et al., 1992; Klimo Jr. et al.,
      2009). We report an unusual case of primary ES of the spine in a two-year-old
      boy, who presented to us with paraparesis and features of cauda equina syndrome.
      MRI scan showed a tumour mass arising from the pedicle of L4 vertebra invading
      the spinal canal. Tc-99 bone scan showed increased tracer uptake in L4 vertebra
      and normal tracer uptake elsewhere in the skeleton. After reaching the diagnosis
      of a space occupying lesion invading the lumber spinal canal, we performed a
      decompressive laminectomy and a biopsy was sent which confirmed the diagnosis of
      ES. Immunohistochemistry showed tumour cells staining positive for CD-99
      (specific stain for ES). Gene testing showed an EWS-FLI 1 chimera. Surgery was
      followed by good improvement in motor signs. The child was then referred to a
      specialized oncotherapy centre for further treatment, radiation, and
      chemotherapy. To the best of our knowledge, we are the first to report primary ES
      of the spine at the age of two years.

PMID- 27895950
TI  - Endobronchial Carcinoid and Concurrent Carcinoid Syndrome in an Adolescent
      Female.
AB  - Endobronchial carcinoid tumors are the most common intrabronchial tumors in
      children and adolescents. Common signs and symptoms include persistent cough and
      wheezing not responsive to bronchodilators, hemoptysis, and recurrent fever.
      Diagnosis is frequently made by imaging and direct visualization with flexible
      bronchoscopy; surgery remains the gold standard treatment, and lung-sparing
      resections should be performed whenever possible. Though carcinoid syndrome
      characterized by flushing, palpitations, wheezing, shortness of breath, and
      diarrhea-has been found in association with adult bronchial carcinoid tumors, to
      our knowledge only one previous study has reported the presence of carcinoid
      syndrome in a pediatric patient with an endobronchial carcinoid. Here, we report
      a case of a 14-year-old girl with chronic cough found to have an endobronchial
      carcinoid tumor and signs and symptoms consistent with carcinoid syndrome.

PMID- 27895951
TI  - Persistent Tachypnea and Alveolar Hemorrhage in an Infant: An Unexpected
      Etiology.
AB  - Persistent tachypnea and failure to thrive during infancy have a broad
      differential diagnosis which includes pulmonary and cardiovascular disorders.
      Diffuse alveolar hemorrhage (DAH) is a rare entity in children. DAH requires an
      extensive work-up as certain conditions may need chronic therapy. Cardiovascular
      disorders are included in the etiology of DAH. We present a case of an 8-month
      old female with a moderate, restrictive patent ductus arteriosus (PDA) admitted
      to the hospital with respiratory distress and failure to thrive. An extensive
      work-up into tachypnea including multiple echocardiograms did not find an
      etiology. Open lung biopsy was performed and consistent with pulmonary
      hypertension. After closure of the PDA, patient's tachypnea improved, and she was
      discharged home with periodic follow-up showing a growing, thriving child. When
      an infant presents with tachypnea, a respiratory viral illness is often a common
      cause. The diagnosis of persistent tachypnea requires further investigation.
      Echocardiography, although readily available, may not always be sensitive in
      detecting clinically significant pulmonary hypertension. A clinician must have a
      heightened index of suspicion to proceed in evaluating for causes of tachypnea
      with a nonrespiratory etiology.

PMID- 27895952
TI  - Severe Hiatal Hernia as a Cause of Failure to Thrive Discovered by Transthoracic
      Echocardiogram.
AB  - A newborn infant with failure to thrive presented for murmur evaluation on day of
      life three due to a harsh 3/6 murmur. During the evaluation, a retrocardiac fluid
      filled mass was seen by transthoracic echocardiogram. The infant was also found
      to have a ventricular septal defect and partial anomalous pulmonary venous
      return. Eventually, a large hiatal hernia was diagnosed on subsequent imaging.
      The infant ultimately underwent surgical repair of the hiatal hernia at a
      tertiary care facility. Hiatal hernias have been noted as incidental extracardiac
      findings in adults, but no previous literature has documented hiatal hernias as
      incidental findings in the pediatric population.

PMID- 27895953
TI  - Rhabdomyolysis in a Hospitalized 16-Year-Old Boy: A Rarely Reported Underlying
      Cause.
AB  - Rhabdomyolysis can occur because of multiple causes and account for 7% of all
      cases of acute kidney injury annually in the United States. Identification of
      specific cause can be difficult in many cases where multiple factors could
      potentially cause rhabdomyolysis. We present a case of 16-year-old male who had
      seizures and was given levetiracetam that resulted in rhabdomyolysis. This side
      effect has been rarely reported previously and like in our case diagnosis may be
      delayed.

PMID- 27895954
TI  - Adult Embryonal Sarcoma of the Liver: Management of a Massive Liver Tumor.
AB  - Undifferentiated embryonal sarcomas of the liver are extremely rare cases in
      adults. We report the case of a 30-year-old male who presented with early satiety
      and abdominal pain due to a massive tumor originating from the left liver and
      occupying the entire epigastrium. The patient underwent bland embolization in an
      attempt to decrease the size of the tumor. He then underwent a formal left
      hepatectomy with resection of liver segments 2, 3, and 4. Extrahepatic inflow
      control of the portal vein and hepatic artery was performed prior to parenchymal
      transection. No Pringle maneuver was required. Pathology analysis showed a 45 cm
      tumor consistent with an undifferentiated embryonal sarcoma and negative
      microscopic margins. The epidemiology, treatment, and prognosis of this unusual
      cancer presentation are reviewed.

PMID- 27895955
TI  - Emerging New Era of Mobile Health Technologies.

PMID- 27895957
TI  - Adoption of Electronic Health Records: A Roadmap for India.
AB  - OBJECTIVES: The objective of the study was to create a roadmap for the adoption
      of Electronic Health Record (EHR) in India based an analysis of the strategies of
      other countries and national scenarios of ICT use in India. METHODS: The
      strategies for adoption of EHR in other countries were analyzed to find the
      crucial steps taken. Apart from reports collected from stakeholders in the
      country, the study relied on the experience of the author in handling several e
      health projects. RESULTS: It was found that there are four major areas where the
      countries considered have made substantial efforts: ICT infrastructure, Policy &
      regulations, Standards & interoperability, and Research, development & education.
      A set of crucial activities were identified in each area. Based on the analysis,
      a roadmap is suggested. It includes the creation of a secure health network;
      health information exchange; and the use of open-source software, a national
      health policy, privacy laws, an agency for health IT standards, R&D, human
      resource development, etc. CONCLUSIONS: Although some steps have been initiated,
      several new steps need to be taken up for the successful adoption of EHR. It
      requires a coordinated effort from all the stakeholders.

PMID- 27895956
TI  - Steps in Moving Evidence-Based Health Informatics from Theory to Practice.
AB  - OBJECTIVES: To demonstrate and promote the importance of applying a scientific
      process to health IT design and implementation, and of basing this on research
      principles and techniques. METHODS: A review by international experts linked to
      the IMIA Working Group on Technology Assessment and Quality Development. RESULTS:
      Four approaches are presented, linking to the creation of national professional
      expectations, adherence to research-based standards, quality assurance approaches
      to ensure safety, and scientific measurement of impact. CONCLUSIONS: Solely
      marketing- and aspiration-based approaches to health informatics applications are
      no longer ethical or acceptable when scientifically grounded evidence-based
      approaches are available and in use.

PMID- 27895958
TI  - Factors Associated with the Timeliness of Electronic Nursing Documentation.
AB  - OBJECTIVES: To investigate the factors associated with the timeliness of
      electronic nursing documentation using the entry time on the Electronic Medical
      Record (EMR) system. METHODS: As a retrospective study, data were extracted from
      January 1 to February 28, 2014 from a hospital EMR system and a nurses' personnel
      information system. The timeliness of instances of nursing documentation was
      categorized into 'timely' or 'untimely' according to whether the entry time was
      time-stamped within the working hours during each day, evening, or night shift.
      Factors associated with the timeliness of the electronic nursing documentation
      were included in the logistic regression models as nurse- and patient-associated
      factors. RESULTS: Among 1,700,247 instances of electronic nursing documentation,
      79.3% (n = 1,347,711) were completed within the working hours. Years of nursing
      experience, nursing shift, days of the week, patients' age, and medical
      department had a statistically significant associated with the timeliness of
      nursing records. Nurses with experience of more than 1 year entered nursing
      records over 2 times more during their working hours than did less experienced
      nurses. During the evening and night shifts, nurses were 1.49 times and 9.19
      times more likely to enter nursing documents in a timely manner, respectively, as
      compared to those in the day shift. CONCLUSIONS: Nursing documentation was
      typically completed outside of working hours when a nurse had little experience,
      worked during the day shift or weekdays, and when tasks were unpredictable. This
      shows that new nurses need support to familiarize them with various tasks and the
      overall workflow.

PMID- 27895959
TI  - Incidence of Adult In-Hospital Cardiac Arrest Using National Representative
      Patient Sample in Korea.
AB  - OBJECTIVES: This study analyzed the incidence and characteristics of in-hospital
      cardiac arrest (IHCA) in Korea based on a sample group of patients that is
      representative of the population. METHODS: The incidence of IHCA in adults was
      extracted from HIRA-NIS-2009, a sample of all patients using medical services in
      Korea. IHCA patients were analyzed according to gender, age, type of medical
      institute, and classification under the 6th revision of the Korean Standard
      Classification of Diseases (KCD-6). In addition, to assess the differences
      arising from the size of medical institutes, the IHCA incidence was analyzed in
      relation to the number of inpatient beds. RESULTS: Based on the sample data, the
      total incidence of IHCA in Korea was found to be 2.46 per 1,000 admissions (95%
      confidence interval [CI], 2.37-2.55). A higher incidence was found among men at
      3.18 (95% CI, 3.03-3.33), compared to women at 1.84 (95% CI, 1.74-1.94). The
      incidence of IHCA was also higher in hospitals that had more than 600 inpatients
      beds at 5.40 (95% CI, 5.16-5.66) in comparison to those that had less than 600
      inpatients beds at 4.09 (95% CI, 3.76-4.36) (p < 0.001). By primary disease, the
      incidence was the highest for infectious diseases. CONCLUSIONS: We demonstrated
      that the IHCA incidence based on gender, age, diagnostic group, and number of
      beds could be analyzed using the insurance claim data from a national
      representative sample.

PMID- 27895960
TI  - Automatic Four-Chamber Segmentation Using Level-Set Method and Split Energy
      Function.
AB  - OBJECTIVES: In this paper, we present an automatic method to segment four
      chambers by extracting a whole heart, separating the left and right sides of the
      heart, and spliting the atrium and ventricle regions from each heart in cardiac
      computed tomography angiography (CTA) efficiently. METHODS: We smooth the images
      by applying filters to remove noise. Next, the volume of interest is detected by
      using k-means clustering. In this step, the whole heart is coarsely extracted,
      and it is used for seed volumes in the next step. Then, we detect seed volumes
      using a geometric analysis based on anatomical information and separate the left
      and right heart regions with the power watershed algorithm. Finally, we refine
      the left and right sides of the heart using the level-set method, and extract the
      atrium and ventricle from the left and right heart regions using the split energy
      function. RESULTS: We tested the proposed heart segmentation method using 20
      clinical scan datasets which were acquired from various patients. To validate the
      proposed heart segmentation method, we evaluated its accuracy in segmenting four
      chambers based on four error evaluation metrics. The average values of
      differences between the manual and automatic segmentations were less than 3.3%,
      approximately. CONCLUSIONS: The proposed method extracts the four chambers of the
      heart accurately, demonstrating that this approach can assist the cardiologist.

PMID- 27895962
TI  - Texture Analysis of Supraspinatus Ultrasound Image for Computer Aided Diagnostic
      System.
AB  - OBJECTIVES: In this paper, we proposed an algorithm for recognizing a rotator
      cuff supraspinatus tendon tear using a texture analysis based on a histogram,
      gray level co-occurrence matrix (GLCM), and gray level run length matrix (GLRLM).
      METHODS: First, we applied a total of 57 features (5 first order descriptors, 40
      GLCM features, and 12 GLRLM features) to each rotator cuff region of interest.
      Our results show that first order statistics (mean, skewness, entropy, energy,
      smoothness), GLCM (correlation, contrast, energy, entropy, difference entropy,
      homogeneity, maximum probability, sum average, sum entropy), and GLRLM features
      are helpful to distinguish a normal supraspinatus tendon and an abnormal
      supraspinatus tendon. The statistical significance of these features is verified
      using a t-test. The support vector machine classification showed accuracy using
      feature combinations. Support Vector Machine offers good performance with a small
      amount of training data. Sensitivity, specificity, and accuracy are used to
      evaluate performance of a classification test. RESULTS: From the results, first
      order statics features and GLCM and GLRLM features afford 95%, 85%, and 100%
      accuracy, respectively. First order statistics and GLCM and GLRLM features in
      combination provided 100% accuracy. Combinations that include GLRLM features had
      high accuracy. GLRLM features were confirmed as highly accurate features for
      classified normal and abnormal. CONCLUSIONS: This algorithm will be helpful to
      diagnose supraspinatus tendon tear on ultrasound images.

PMID- 27895961
TI  - Automated Detection Algorithm of Breast Masses in Three-Dimensional Ultrasound
      Images.
AB  - OBJECTIVES: We propose an automatic breast mass detection algorithm in three
      dimensional (3D) ultrasound (US) images using the Hough transform technique.
      METHODS: One hundred twenty-five cropped images containing 68 benign and 60
      malignant masses are acquired with clinical diagnosis by an experienced
      radiologist. The 3D US images are masked, subsampled, contrast-adjusted, and
      median-filtered as preprocessing steps before the Hough transform is used.
      Thereafter, we perform 3D Hough transform to detect spherical hyperplanes in 3D
      US breast image volumes, generate Hough spheres, and sort them in the order of
      votes. In order to reduce the number of the false positives in the breast mass
      detection algorithm, the Hough sphere with a mean or grey level value of the
      centroid higher than the mean of the 3D US image is excluded, and the remaining
      Hough sphere is converted into a circumscribing parallelepiped cube as breast
      mass lesion candidates. Finally, we examine whether or not the generated Hough
      cubes were overlapping each other geometrically, and the resulting Hough cubes
      are suggested as detected breast mass candidates. RESULTS: An automatic breast
      mass detection algorithm is applied with mass detection sensitivity of 96.1% at
      0.84 false positives per case, quite comparable to the results in previous
      research, and we note that in the case of malignant breast mass detection, every
      malignant mass is detected with false positives per case at a rate of 0.62.
      CONCLUSIONS: The breast mass detection efficiency of our algorithm is assessed by
      performing a ROC analysis.

PMID- 27895963
TI  - Evaluation of Semi-automatic Segmentation Methods for Persistent Ground Glass
      Nodules on Thin-Section CT Scans.
AB  - OBJECTIVES: This work was a comparative study that aimed to find a proper method
      for accurately segmenting persistent ground glass nodules (GGN) in thin-section
      computed tomography (CT) images after detecting them. METHODS: To do this, we
      first applied five types of semi-automatic segmentation methods (i.e., level-set
      based active contour model, localized region-based active contour model, seeded
      region growing, K-means clustering, and fuzzy C-means clustering) to preprocessed
      GGN images, respectively. Then, to measure the similarities, we calculated the
      Dice coefficient of the segmented area using each semiautomatic method with the
      result of the manually segmented area by two radiologists. RESULTS: Comparison
      experiments were performed using 40 persistent GGNs. In our experiment, the mean
      Dice coefficient for each semiautomatic segmentation tool with manually segmented
      area was 0.808 for the level-set-based active contour model, 0.8001 for the
      localized region-based active contour model, 0.629 for seeded region growing,
      0.7953 for K-means clustering, and 0.7999 for fuzzy C-means clustering,
      respectively. CONCLUSIONS: The level-set-based active contour model algorithm
      showed the best performance, which was most similar to the result of manual
      segmentation by two radiologists. From the differentiation between the normal
      parenchyma and the nodule, it was also the most efficient. Effective segmentation
      methods will be essential for the development of computer-aided diagnosis systems
      for more accurate early diagnosis and prognosis of lung cancer in thin-section CT
      images.

PMID- 27895964
TI  - Half-Fan-Based Intensity-Weighted Region-of-Interest Imaging for Low-Dose Cone
      Beam CT in Image-Guided Radiation Therapy.
AB  - OBJECTIVES: With the increased use of computed tomography (CT) in clinics, dose
      reduction is the most important feature people seek when considering new CT
      techniques or applications. We developed an intensity-weighted region-of-interest
      (IWROI) imaging method in an exact half-fan geometry to reduce the imaging
      radiation dose to patients in cone-beam CT (CBCT) for image-guided radiation
      therapy (IGRT). While dose reduction is highly desirable, preserving the high
      quality images of the ROI is also important for target localization in IGRT.
      METHODS: An intensity-weighting (IW) filter made of copper was mounted in place
      of a bowtie filter on the X-ray tube unit of an on-board imager (OBI) system such
      that the filter can substantially reduce radiation exposure to the outer ROI. In
      addition to mounting the IW filter, the lead-blade collimation of the OBI was
      adjusted to produce an exact half-fan scanning geometry for a further reduction
      of the radiation dose. The chord-based rebinned backprojection-filtration (BPF)
      algorithm in circular CBCT was implemented for image reconstruction, and a
      humanoid pelvis phantom was used for the IWROI imaging experiment. RESULTS: The
      IWROI image of the phantom was successfully reconstructed after beam-quality
      correction, and it was registered to the reference image within an acceptable
      level of tolerance. Dosimetric measurements revealed that the dose is reduced by
      approximately 61% in the inner ROI and by 73% in the outer ROI compared to the
      conventional bowtie filter-based half-fan scan. CONCLUSIONS: The IWROI method
      substantially reduces the imaging radiation dose and provides reconstructed
      images with an acceptable level of quality for patient setup and target
      localization. The proposed half-fan-based IWROI imaging technique can add a
      valuable option to CBCT in IGRT applications.

PMID- 27895966
TI  - Acceptability of Service Targets for ICT-Based Healthcare.
AB  - OBJECTIVES: In order to adopt and activate telemedicine it is necessary to survey
      how medical staff, who are providers of medical service, and consumers, who are
      the service targets, perceive information and communication technology (ICT)
      based healthcare service. METHODS: This study surveyed the awareness and
      acceptability of ICT-based healthcare by involving service targets, specifically
      workers and students living in the Seoul and Gyeonggi regions who are consumers
      of healthcare service. To determine the correlation among awareness of ICT-based
      healthcare, the need for self-management, and acceptability, this study conducted
      a correlation analysis and a simple regression analysis. RESULTS: According to
      the responses to the questions on the need for ICT-based healthcare service by
      item, blood pressure (n = 279, 94.3%) and glucose (n = 277, 93.6%) were revealed
      to be the physiological signal monitoring area. Among the six measurement factors
      affecting ICT-based healthcare service acceptability, age, health concerns, and
      effect expectation had the most significant effects. As effect expectation
      increased, acceptability became 4.38 times higher (p < 0.05). CONCLUSIONS: This
      study identified a positive awareness of service targets on ICT-based healthcare
      service. The fact that acceptability is higher among people who have family
      disease history or greater health concerns may lead to service targets' more
      active participation. This study also confirmed that a policy to motivate active
      participation of those in their 40s (who had high prevalence rates) was needed.

PMID- 27895965
TI  - Confirmation of Expectations and Satisfaction with Hospital Information Systems:
      A Nursing Perspective.
AB  - OBJECTIVES: This study aimed to compare nurses' satisfaction with, and
      expectations of, hospital information systems in two teaching hospitals. METHODS:
      This was a survey study, which was completed in 2014. The potential participants
      were 267 nurses who worked in two teaching hospitals and used the same hospital
      information system. Data were collected using two questionnaires. Both
      questionnaires were examined in terms of content validity and reliability.
      RESULTS: The results showed that, for a majority of nurses, their expectations of
      the system were not met in either hospital. Moreover, there was a significant
      association between the nurses' expectations and the perceived usefulness of the
      systems (p < 0.001), between the nurses' expectations and their satisfaction with
      the systems (p < 0.001), and between the perceived usefulness and nurses'
      satisfaction with the systems (p < 0.001). CONCLUSIONS: The results suggested
      that, apart from the technical issues of implementing clinical information
      systems, non-technical factors should be taken into account. Among them, the
      nature of clinical tasks and the organizational culture require more attention to
      allow a successful system to be designed and implemented.

PMID- 27895967
TI  - Medical Representatives' Intention to Use Information Technology in
      Pharmaceutical Marketing.
AB  - OBJECTIVES: Electronic detailing (e-detailing), the use of electronic devices to
      facilitate sales presentations to physicians, has been adopted and expanded in
      the pharmaceutical industry. To maximize the potential outcome of e-detailing, it
      is important to understand medical representatives (MRs)' behavior and attitude
      to e-detailing. This study investigates how information technology devices such
      as laptop computers and tablet PCs are utilized in pharmaceutical marketing, and
      it analyzes the factors influencing MRs' intention to use devices. METHODS: This
      study has adopted and modified the theory of Roger's diffusion of innovation
      model and the technology acceptance model. To test the model empirically, a
      questionnaire survey was conducted with 221 MRs who were working in three
      multinational or eleven domestic pharmaceutical companies in Korea. RESULTS:
      Overall, 28% and 35% of MRs experienced using laptop computers and tablet PCs in
      pharmaceutical marketing, respectively. However, the rates were different across
      different groups of MRs, categorized by age, education level, position, and
      career. The results showed that MRs' intention to use information technology
      devices was significantly influenced by perceived usefulness in general.
      Perceived ease of use, organizational and individual innovativeness, and several
      MR characteristics were also found to have significant impacts. CONCLUSIONS: This
      study provides timely information about e-detailing devices to marketing managers
      and policy makers in the pharmaceutical industry for successful marketing
      strategy development by understanding the needs of MRs' intention to use
      information technology. Further in-depth study should be conducted to understand
      obstacles and limitations and to improve the strategies for better marketing
      tools.

PMID- 27895968
TI  - Correction: Methods of Hematoxylin and Eosin Image Information Acquisition and
      Optimization in Confocal Microscopy.
AB  - [This corrects the article on p. 238 in vol. 22, PMID: 27525165.].

PMID- 27895969
TI  - Genetic Advances in Craniofacial Malformations.

PMID- 27895970
TI  - Genetic Advances in Microphthalmia.
AB  - Congenital ocular anomalies such as anophthalmia and microphthalmia (AM) are
      severe craniofacial malformations in human. The etiologies of these ocular globe
      anomalies are diverse but the genetic origin appears to be a predominant cause.
      Until recently, genetic diagnosis capability was rather limited in AM patients
      and only a few genes were available for routine genetic testing. While some
      issues remain poorly understood, knowledge regarding the molecular basis of AM
      dramatically improved over the last years with the development of new molecular
      screening technologies. Thus, the genetic cause is now identifiable in more than
      50% of patients with a severe bilateral eye phenotype and in around 30% of all AM
      patients taken together. Such advances in the knowledge of these genetic bases
      are important as they improve the quality of care, in terms of diagnosis,
      prognosis, and genetic counseling delivered to the patients and their families.

PMID- 27895971
TI  - Genetic Advances in the Understanding of Microtia.
AB  - Microtia is a genetic condition affecting the external ears and presents
      clinically along a wide spectrum: minimally affected ears are small with minor
      shape abnormalities; extremely affected ears lack all identifiable structures,
      with the most extreme being absence of the entire external ear. Multiple genetic
      causes have been linked to microtia in both animal models and humans, which are
      improving our understanding of the condition and may lead to the identification
      of a unified cause for the condition. Microtia is also a prominent feature of
      several genetic syndromes, the study of which has provided further insight into
      the possible causes and genetic mechanisms of the condition. This article reviews
      our current understanding of microtia including epidemiological characteristics,
      classification systems, environmental and genetic causative factors leading to
      microtia. Despite our increased understanding of the genetics of microtia, we do
      not have a means of preventing the condition and still rely on complex staged,
      surgical correction.

PMID- 27895972
TI  - Genetic Basis of Nonsyndromic and Syndromic Tooth Agenesis.
AB  - Human dentition development is a long and complex process which involves a series
      of reciprocal and sequential interactions between the embryonic stomodeal
      epithelium and the underlying neural crest-derived mesenchyme. Despite
      environment disturbances, tooth development is predominantly genetically
      controlled. To date, more than 200 genes have been identified in tooth
      development. These genes implied in various signaling pathways such as the bone
      morphogenetic protein, fibroblast growth factor, sonic hedgehog homolog,
      ectodysplasin A, wingless-type MMTV integration site family (Wnt), and transform
      growth factor pathways. Mutations in any of these strictly balanced signaling
      cascades may cause arrested odontogenesis and/or other dental defects. This
      article aims to review current knowledge about the genetic mechanisms responsible
      for selective nonsyndromic tooth agenesis in humans and to present a detailed
      summary of syndromes with hypodontia as regular features and their causative
      genes.

PMID- 27895973
TI  - Review of the Genetic Basis of Jaw Malformations.
AB  - Genetic etiologies for congenital anomalies of the facial skeleton, namely, the
      maxilla and mandible, are important to understand and recognize. Malocclusions
      occur when there exist any significant deviation from what is considered a normal
      relationship between the upper jaw (maxilla) and the lower jaw (mandible). They
      may be the result of anomalies of the teeth alone, the bones alone, or both. A
      number of genes play a role in the facial skeletal development and are regulated
      by a host of additional regulatory molecules. As such, numerous craniofacial
      syndromes specifically affect the development of the jaws. The following review
      discusses several genetic anomalies that specifically affect the bones of the
      craniofacial skeleton and lead to malocclusion.

PMID- 27895974
TI  - Genetic Screening in Patients with Craniofacial Malformations.
AB  - Craniofacial malformations include a variety of anomalies, including cleft lip
      with or without cleft palate, craniosynostosis, microtia, and hemifacial
      microsomia. All of these anomalies can be either isolated or part of a defined
      genetic syndrome. A clinical geneticist or genetic counselor should be a member
      of the craniofacial team to help determine which patients have isolated anomalies
      and which are likely to have a syndrome. They would then arrange for the
      appropriate genetic testing to confirm the diagnosis of the specific syndrome.
      The identification of the specific syndrome is important for the overall care of
      the patient (as it identifies risk for other medical problems such as congenital
      heart defect) that will have to be taken into account in the care of the
      craniofacial malformation. In addition, knowing the specific syndrome will allow
      the family to understand how this happened to their child and the recurrence risk
      for future pregnancies. With the advent of new technologies, there are now many
      types of genetic testing available (including, karyotype, fluorescence in situ
      hybridization, chromosomal microarrays, and next generation sequencing) and the
      medical geneticist and genetic counselor can determine which specific testing is
      needed for a given patient.

PMID- 27895975
TI  - Anti-Helicobacter pylori effect of CaG-NANA, a new sialic acid derivative.
AB  - AIM: To investigate the bactericidal effects of calcium chelated N
      acetylneuraminic acid-glycomacropeptide (CaG-NANA) against Helicobacter pylori
      (H. pylori). METHODS: For manufacture of CaG-NANA, calcium (Ca) was combined with
      glycomacropeptide (GMP) by chelating, and N-acetylneuraminic acid (NANA) was
      produced with Ca-GMP substrate by an enzymatic method. The final concentration of
      each component was 5% Ca, 7% NANA, 85% GMP, and 3% water. For in vitro study,
      various concentrations of CaG-NANA were investigated under the minimal inhibitory
      concentration (MIC). For in vivo study, CaG-NANA was administered orally for 3 wk
      after H. pylori infection. The levels of inflammatory cytokines in blood were
      analyzed by enzyme-linked immunosorbent assay and eradication of H. pylori was
      assessed by histological observation. RESULTS: The time-kill curves showed a
      persistent decrease in cell numbers, which depended on the dose of CaG-NANA, and
      MIC of CaG-NANA against H. pylori was 0.5% in vitro. Histopathologic observation
      revealed no obvious inflammation or pathologic changes in the gastric mucosa in
      the CaG-NANA treatment group in vivo. The colonization of H. pylori was reduced
      after CaG-NANA treatment. The levels of interleukin (IL)-6, IL-1beta, tumor
      necrosis factor-alpha, and IL-10 were also decreased by CaG-NANA. CONCLUSION: CaG
      NANA demonstrates effective anti-bactericidal activity against H. pylori both in
      vitro and in vivo.

PMID- 27895976
TI  - Microscopic colitis in patients with mild duodenal damage: A new clinical and
      pathological entity ("lymphocytic enterocolitis")?
AB  - AIM: To evaluate the potential association between mild duodenal damage and
      microscopic colitis (MC). METHODS: We retrospectively included 105 consecutive
      patients with type I Marsh-Oberhuber duodenal damage and negativity for
      immunoglobulin A anti-endomysium and anti-tissue transglutaminase. The following
      parameters were analyzed: Sex, age at execution of esophagogastroduodenoscopy,
      duodenal damage, and number of intraepithelial lymphocytes at biopsies,
      prevalence of Helicobacter pylori infection, age at execution of colonoscopy,
      macroscopic and microscopic features of colonoscopy, family history of
      gastrointestinal and autoimmune diseases, smoking habits, biochemical parameters
      of inflammation and autoimmunity, use of proton pump inhibitors or nonsteroidal
      anti-inflammatory drugs, adverse reactions to drugs or foods, pathologies known
      to be associated with celiac disease or MC, living on a gluten-free diet or on a
      gluten-low diet for at least 1 mo. RESULTS: Colonoscopy was performed in 59
      patients, but only in 48 of them biopsies were taken in the entire colon.
      Considering the latter cohort, the diagnosis of MC was met in 25 (52.1%) patients
      while in 18 patients other pathologic findings were reported: 13 (27%) cases of
      nonspecific inflammatory bowel disease, 2 (4.2%) cases of Crohn's disease, 2
      (4.2%) cases of eosinophilic gastroenteritis, and 1 (2.1%) case of autoimmune
      enteritis. Five (10.4%) patients had a normal colonoscopic result. Matching the
      groups by age, and considering only patients who underwent colonoscopy (42.7 +/-
      15.5 years) vs those who did not undergo colonoscopy (36.9 +/- 10.6 years), a
      statistical difference was found (P = 0.039). Focusing on symptoms, diarrhea was
      statistically more prevalent in MC group than in patients who did not undergo
      colonoscopy (P = 0.03). CONCLUSION: Mild duodenal damage is associated with MC in
      more than half of the cases. This association supports the hypothesis of a link
      between these two entities.

PMID- 27895977
TI  - Hepatitis C infection and renal cell carcinoma: A systematic review and meta
      analysis.
AB  - AIM: To investigate the association between hepatitis C virus (HCV) infection and
      risk of renal cell carcinoma (RCC). METHODS: A literature search was performed
      from inception until February 2016. Studies that reported relative risks, odd
      ratios, hazard ratios or standardized incidence ratio comparing the risk of RCC
      among HCV-infected participants vs those without HCV infection were included.
      Participants without HCV infection were used as comparators. Pooled odds ratios
      and 95%CI were calculated using a random-effect, generic inverse variance method.
      RESULTS: Seven observational studies were with 196826 patients were included in
      the analysis to assess the risk of RCC in patients with HCV. A significantly
      increased risk of RCC among participants with HCV infection was found with a
      pooled RR of 1.86 (95%CI: 1.11-3.11). The association between RCC and HCV was
      marginally insignificant after a sensitivity analysis limited only to studies
      with adjusted analysis, with a pooled RR of 1.50 (95%CI: 0.93-2.42). CONCLUSION:
      Our study demonstrated a potential association between HCV infection and RCC.
      Further studies of RCC surveillance in patients with HCV are required.

PMID- 27895979
TI  - Optical redox ratio identifies metastatic potential-dependent changes in breast
      cancer cell metabolism.
AB  - The development of prognostic indicators of breast cancer metastatic risk could
      reduce the number of patients receiving chemotherapy for tumors with low
      metastatic potential. Recent evidence points to a critical role for cell
      metabolism in driving breast cancer metastasis. Endogenous fluorescence intensity
      of nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD)
      can provide a label-free method for assessing cell metabolism. We report the
      optical redox ratio of FAD/(FAD + NADH) of four isogenic triple-negative breast
      cancer cell lines with varying metastatic potential. Under normoxic conditions,
      the redox ratio increases with increasing metastatic potential
      (168FARN>4T07>4T1), indicating a shift to more oxidative metabolism in cells
      capable of metastasis. Reoxygenation following acute hypoxia increased the redox
      ratio by 43 +/- 9% and 33 +/- 4% in the 4T1 and 4T07 cells, respectively; in
      contrast, the redox ratio decreased 14 +/- 7% in the non-metastatic 67NR cell
      line. These results demonstrate that the optical redox ratio is sensitive to the
      metabolic adaptability of breast cancer cells with high metastatic potential and
      could potentially be used to measure dynamic functional changes that are
      indicative of invasive or metastatic potential.

PMID- 27895980
TI  - Rapid mesoscale multiphoton microscopy of human skin.
AB  - We present a multiphoton microscope designed for mesoscale imaging of human skin.
      The system is based on two-photon excited fluorescence and second-harmonic
      generation, and images areas of ~0.8x0.8 mm2 at speeds of 0.8 fps (800x800
      pixels; 12 frame averages) for high signal-to-noise ratio, with lateral and axial
      resolutions of 0.5um and 3.3um, respectively. The main novelty of this instrument
      is the design of the scan head, which includes a fast galvanometric scanner,
      optimized relay optics, a beam expander and high NA objective lens. Computed
      aberrations in focus are below the Marechal criterion of 0.07lambda rms for
      diffraction-limited performance. We demonstrate the practical utility of this
      microscope by ex-vivo imaging of wide areas in normal human skin.

PMID- 27895981
TI  - Perceived image quality with simulated segmented bifocal corrections.
AB  - Bifocal contact or intraocular lenses use the principle of simultaneous vision to
      correct for presbyopia. A modified two-channel simultaneous vision simulator
      provided with an amplitude transmission spatial light modulator was used to
      optically simulate 14 segmented bifocal patterns (+ 3 diopters addition) with
      different far/near pupillary distributions of equal energy. Five subjects with
      paralyzed accommodation evaluated image quality and subjective preference through
      the segmented bifocal corrections. There are strong and systematic perceptual
      differences across the patterns, subjects and observation distances: 48% of the
      conditions evaluated were significantly preferred or rejected. Optical
      simulations (in terms of through-focus Strehl ratio from Hartmann-Shack
      aberrometry) accurately predicted the pattern producing the highest perceived
      quality in 4 out of 5 patients, both for far and near vision. These perceptual
      differences found arise primarily from optical grounds, but have an important
      neural component.

PMID- 27895982
TI  - Extended-focus optical coherence microscopy for high-resolution imaging of the
      murine brain.
AB  - We propose a new method and optical instrumentation for mouse brain imaging based
      on extended-focus optical coherence microscopy. This in vivo imaging technique
      allows the evaluation of the cytoarchitecture at cellular level and the
      circulation system dynamics in three dimensions. This minimally invasive and non
      contact approach is performed without the application of contrasting agents. The
      optical design achieved a resolution of 2.2 MUm over a distance of 800 MUm, which
      was sufficient to obtain a detailed three-dimensional image of a wild-type
      mouse's brain down to the layer III of the cortex. Intrinsically contrasted
      microvessels and structures similar to the bodies of neurons were
      distinguishable.

PMID- 27895983
TI  - Introduction to the BIOMED 2016 feature issue.
AB  - The guest editors introduce a feature issue containing papers based on research
      presented at the BIOMED 2016 Congress, held in Fort Lauderdale, FL, 24-28 April,
      2016.

PMID- 27895978
TI  - Cytokines and Cytokine Receptors Involved in the Pathogenesis of Alzheimer's
      Disease.
AB  - Inflammatory mechanisms are implicated in the pathology of Alzheimer's disease
      (AD). However, it is unclear whether inflammatory alterations are a cause or
      consequence of neurodegeneration leading to dementia. Clarifying this issue would
      provide valuable insight into the early diagnosis and therapeutic management of
      AD. To address this, we compared the mRNA expression profiles of cytokines in the
      brains of AD patients with "non-demented individuals with AD pathology" and non
      demented healthy control (ND) individuals. "Non-demented individuals with AD
      pathology" are referred to as high pathology control (HPC) individuals that are
      considered an intermediate subset between AD and ND. HPC represents a transition
      between normal aging and early stage of AD, and therefore, is useful for
      determining whether neuroinflammation is a cause or consequence of AD pathology.
      We observed that immunological conditions that produce cytokines in the HPC brain
      were more representative of ND than AD. To validate these result, we investigated
      the expression of inflammatory mediators at the protein level in postmortem brain
      tissues. We examined the protein expression of tumor necrosis factor (TNF)alpha
      and its receptors (TNFRs) in the brains of AD, HPC, and ND individuals. We found
      differences in soluble TNFalpha and TNFRs expression between AD and ND groups and
      between AD and HPC groups. Expression in the temporal cortex was lower in the AD
      brains than HPC and ND. Our findings indicate that alterations in immunological
      conditions involving TNFR-mediated signaling are not the primary events
      initiating AD pathology, such as amyloid plaques and tangle formation. These may
      be early events occurring along with synaptic and neuronal changes or later
      events caused by these changes. In this review, we emphasize that elucidating the
      temporal expression of TNFalpha signaling molecules during AD is important to
      understand the selective tuning of these pathways required to develop effective
      therapeutic strategies for AD.

PMID- 27895984
TI  - Fabrication and analysis of microfiber array platform for optogenetics with
      cellular resolution.
AB  - Optogenetics has emerged as a revolutionary technology especially for
      neuroscience and has advanced continuously over the past decade. Conventional
      approaches for patterned in vivo optical illumination have a limitation on the
      implanted device size and achievable spatio-temporal resolution. In this work, we
      developed a fabrication process for a microfiber array platform. Arrayed
      poly(methyl methacrylate) (PMMA) microfibers were drawn from a polymer solution
      and packaged with polydimethylsiloxane (PDMS). The exposed end face of a packaged
      microfiber was tuned to have a size corresponding to a single cell. To
      demonstrate its capability for single cell optogenetics, HEK293T cells expressing
      channelrhodopsin-2 (ChR2) were cultured on the platform and excited with UV
      laser. We could then observe an elevation in the intracellular Ca2+
      concentrations due to the influx of Ca2+ through the activated ChR2 into the
      cytosol. The statistical and simulation results indicate that the proposed
      microfiber array platform can be used for single cell optogenetic applications.

PMID- 27895986
TI  - Combined frequency domain photoacoustic and ultrasound imaging for intravascular
      applications.
AB  - Intravascular photoacoustic (IVPA) imaging has the potential to characterize
      lipid-rich structures based on the optical absorption contrast of tissues. In
      this study, we explore frequency domain photoacoustics (FDPA) for intravascular
      applications. The system employed an intensity-modulated continuous wave (CW)
      laser diode, delivering 1W over an intensity modulated chirp frequency of 4
      12MHz. We demonstrated the feasibility of this approach on an agar vessel phantom
      with graphite and lipid targets, imaged using a planar acoustic transducer co
      aligned with an optical fibre, allowing for the co-registration of IVUS and FDPA
      images. A frequency domain correlation method was used for signal processing and
      image reconstruction. The graphite and lipid targets show an increase in FDPA
      signal as compared to the background of 21dB and 16dB, respectively. Use of
      compact CW laser diodes may provide a valuable alternative for the development of
      photoacoustic intravascular devices instead of pulsed laser systems.

PMID- 27895985
TI  - Multi-channel multi-distance broadband near-infrared spectroscopy system to
      measure the spatial response of cellular oxygen metabolism and tissue
      oxygenation.
AB  - We present a multi-channel, multi-distance broadband near-infrared spectroscopy
      (NIRS) system with the capability of measuring changes in haemoglobin
      concentrations (Delta[HbO2], Delta[HHb]), oxidation state of cytochrome-c-oxidase
      (Delta[oxCCO]) and tissue oxygen saturation (TOI) in the adult human brain. The
      main components of the instrument are two customized spectrographs and two light
      sources. Each spectrograph is lens-based to improve light throughput, has a
      grating enhanced to optimise reflection in the near-infrared (NIR) spectral
      region and uses a front illuminated cooled CCD camera (-70 degrees  C) with a
      square chip dimension of 12.3 x 12.3 mm (512 x 512 pixels). Each light source
      uses a 50W halogen bulb with a gold plated mirror to increase the intensity of
      the NIR light. Each light source was connected to a custom-built bifurcated fibre
      bundle to create two source fibre bundles (3.2 mm diameter each). Each
      spectrograph received light input from another custom-built fibre bundle
      comprised of six individual bundles (one with 0.6 mm diameter and the other five
      with 1.5 mm diameter). All fibre bundles were fixed on a 3D printed optode holder
      (two light sources x two fibre bundles each = four probes; and two spectrographs
      x six fibre bundles each = 12 probes) that allowed 24 multi-distance channels
      across the forehead (six channels at 20 mm, three channels at 30 mm and 15
      channels at 35 mm) and six TOI measurements. We demonstrated the use of the
      system in a cohort of nine healthy adult volunteers during prefrontal cortex
      functional activation using the Stroop task. We have observed functional
      responses identified as significant increase in Delta[HbO2], decrease in
      Delta[HHb] and increase in Delta[oxCCO] in five channels (out of 12), that
      overlay the left and right dorsolateral prefrontal cortices. There was no
      observable TOI functional response and we have shown small variations in TOI
      across different sites within the same subject and within the same site across
      subjects.

PMID- 27895988
TI  - Terahertz identification and quantification of neurotransmitter and neurotrophy
      mixture.
AB  - Terahertz spectroscopy has been widely used for investigating the fingerprint
      spectrum of different substances. For cancerous tissues, the greatest difficulty
      is the absorption peaks of various substances contained in tissues overlap with
      each other, which are hard to identify and quantitative analyze. As a result, it
      is very hard to measure the presence of cancer cell and then to diagnose
      accurately. In this paper, we select three typical neurotransmitters (gamma
      aminobutyric acid, L-glutamic acid, dopamine hydrochloride) and two typical
      metabolites (inositol and creatine) in neurons to measure their terahertz spectra
      with different mixture ratios. By choosing characteristic absorption peaks,
      removing baseline and using the least square method, we can identify the
      components and proportions of each mixture, where the goodness of fit to
      practical situation is up to 94%. These results provide important evidences for
      identifying nerve substances and obtaining exact quantitative analysis.

PMID- 27895987
TI  - Characterization of fiber-optic light delivery and light-induced temperature
      changes in a rodent brain for precise optogenetic neuromodulation.
AB  - Understanding light intensity and temperature increase is of considerable
      importance in designing or performing in vivo optogenetic experiments. Our study
      describes the optimal light power at target depth in the rodent brain that would
      maximize activation of light-gated ion channels while minimizing temperature
      increase. Monte Carlo (MC) simulations of light delivery were used to provide a
      guideline for suitable light power at a target depth. In addition, MC simulations
      with the Pennes bio-heat model using data obtained from measurements with a
      temperature-measuring cannula having 12.3 mV/ degrees C of thermoelectric
      sensitivity enabled us to predict tissue heating of 0.116  degrees C/mW on
      average at target depth of 563 MUm and specifically, a maximum mean plateau
      temperature increase of 0.25  degrees C/mW at 100 MUm depth for 473 nm light. Our
      study will help to improve the design and performance of optogenetic experiments
      while avoiding potential over- and under-illumination.

PMID- 27895989
TI  - Diet-induced obesity skin changes monitored by in vivo SHG and ex vivo CARS
      microscopy.
AB  - Obesity related metabolic syndrome and type 2 diabetes have severe consequences
      on our skin. Latest developments in nonlinear microscopy allow the use of
      noninvasive, label free imaging methods, such as second harmonic generation (SHG)
      and coherent anti-Stokes Raman scattering (CARS), for early diagnosis of
      metabolic syndrome-related skin complications by 3D imaging of the skin and the
      connective tissue. Our aim was to study effects of various types of diet-induced
      obesity in mice using these methods. We examined mice on different diets for 32
      weeks. The collagen morphology was evaluated four times in vivo by SHG
      microscopy, and adipocytes were examined once at the end of experiment by ex vivo
      CARS method. A strong correlation was found between the body weight and the
      adipocyte size, while we found that the SHG intensity of dermal collagen reduces
      considerably with increasing body weight. Obese mice on high-fat diet showed
      worse results than those on high-fat - high-fructose diet. Animals on high
      fructose diet did not gain more weight than those on ordinary diet despite of the
      increased calorie intake, but their collagen damage was nonetheless significant.
      Obesity and high sugar intake damages the skin, mainly the dermal connective
      tissue and subcutaneous adipose tissue, which efficiently can be monitored by in
      vivo SHG and ex vivo CARS microscopy.

PMID- 27895990
TI  - Influence of coherence length, signal-to-noise ratio, log transform, and low-pass
      filtering on layer thickness assessment with OCT in the retina.
AB  - Optical coherence tomography (OCT) images of the retina are inevitably affected
      by the finite width of the coherence function and noise. To make low-reflective
      layers visible, the raw OCT signal is log transformed; to reduce the effect of
      noise the images can be low-pass filtered. We determined the effects of these
      operations on layer thickness assessment, as a function of signal-to-noise ratio
      (SNR), by performing measurements in a phantom eye and modeling. The log
      transform appeared to be the key factor in a SNR-dependent overestimation of peak
      widths and a less predictive bias in the widths of low-reflective layers.

PMID- 27895991
TI  - Intracellular dynamics measurements with full field optical coherence tomography
      suggest hindering effect of actomyosin contractility on organelle transport.
AB  - Intracellular motion can be quantitatively monitored in tissues using coherence
      gated microscopic techniques. With full-field optical coherence tomography
      (FFOCT), the use of high numerical aperture microscope objectives provides a high
      resolution mapping of intracellular dynamics that are probed with subwavelength
      sensitivity. In the upper temporal bandwidth that we have used (1-6 Hz) the main
      contribution to the dynamic signal arises from the overall dynamical, optically
      heterogeneous cytoplasm. We propose a method to specifically study the impact of
      actomyosin contractility on the intracellular dynamic signal by performing high
      throughput, comparative measurements of multicellular aggregates with and without
      blebbistatin action, a selective inhibitor of class-II myosins that disrupts
      actomyosin contractile activity. Our results indicate a significant increase in
      the fraction of the signal that decorrelates within 1 second after inhibition of
      contractility. This observation mitigates the anticipated importance of
      actomyosin contractile forces to directly move organelles, but highlights their
      role in hindering organelle transport via their stiffening effect of the
      viscoelastic cytoplasm.

PMID- 27895992
TI  - Subtraction-based approach for enhancing the depth sensitivity of time-resolved
      NIRS.
AB  - The aim of this study was to evaluate enhancing of the depth sensitivity of time
      resolved near-infrared spectroscopy with a subtraction-based approach. Due to the
      complexity of light propagation in a heterogeneous media, and to prove the
      validity of the proposed method in a heterogeneous turbid media we conducted a
      broad analysis taking into account a number of parameters related to the method
      as well as various parameters of this media. The results of these experiments
      confirm that the depth sensitivity of the subtraction-based approach is better
      than classical approaches using continuous-wave or time-resolved methods.
      Furthermore, the results showed that the subtraction-based approach has a unique,
      selective sensitivity to a layer at a specific depth. In vivo application of the
      proposed method resulted in a greater magnitude of the hemodynamic changes during
      functional activation than with the standard approach.

PMID- 27895993
TI  - Non-stationary reconstruction for dynamic fluorescence molecular tomography with
      extended kalman filter.
AB  - Dynamic fluorescence molecular tomography (FMT) plays an important role in drug
      delivery research. However, the majority of current reconstruction methods focus
      on solving the stationary FMT problems. If the stationary reconstruction methods
      are applied to the time-varying fluorescence measurements, the reconstructed
      results may suffer from a high level of artifacts. In addition, based on the
      stationary methods, only one tomographic image can be obtained after scanning one
      circle projection data. As a result, the movement of fluorophore in imaged object
      may not be detected due to the relative long data acquisition time (typically >1
      min). In this paper, we apply extended kalman filter (EKF) technique to solve the
      non-stationary fluorescence tomography problem. Especially, to improve the EKF
      reconstruction performance, the generalized inverse of kalman gain is calculated
      by a second-order iterative method. The numerical simulation, phantom, and in
      vivo experiments are performed to evaluate the performance of the method. The
      experimental results indicate that by using the proposed EKF-based second-order
      iterative (EKF-SOI) method, we cannot only clearly resolve the time-varying
      distributions of fluorophore within imaged object, but also greatly improve the
      reconstruction time resolution (~2.5 sec/frame) which makes it possible to detect
      the movement of fluorophore during the imaging processes.

PMID- 27895994
TI  - Motion-corrected Fourier ptychography.
AB  - Fourier ptychography (FP) is a recently proposed computational imaging technique
      for high space-bandwidth product imaging. In real setups such as endoscope and
      transmission electron microscope, the common sample motion largely degrades the
      FP reconstruction and limits its practicability. In this paper, we propose a
      novel FP reconstruction method to efficiently correct for unknown sample motion.
      Specifically, we adaptively update the sample's Fourier spectrum from low spatial
      frequency regions towards high spatial-frequency ones, with an additional motion
      recovery and phase-offset compensation procedure for each sub-spectrum.
      Benefiting from the phase retrieval redundancy theory, the required large overlap
      between adjacent sub-spectra offers an accurate guide for successful motion
      recovery. Experimental results on both simulated data and real captured data show
      that the proposed method can correct for unknown sample motion with its standard
      deviation being up to 10% of the field-of-view scale. We have released our source
      code for non-commercial use, and it may find wide applications in related FP
      platforms such as endoscopy and transmission electron microscopy.

PMID- 27895995
TI  - Photoreceptor disc shedding in the living human eye.
AB  - Cone photoreceptors undergo a daily cycle of renewal and shedding of membranous
      discs in their outer segments (OS), the portion responsible for light capture.
      These physiological processes are fundamental to maintaining photoreceptor
      health, and their dysfunction is associated with numerous retinal diseases. While
      both processes have been extensively studied in animal models and postmortem
      eyes, little is known about them in the living eye, in particular human. In this
      study, we report discovery of the optical signature associated with disc shedding
      using a method based on adaptive optics optical coherence tomography (AO-OCT) in
      conjunction with post-processing methods to track and monitor individual cone
      cells in 4D. The optical signature of disc shedding is characterized by an abrupt
      transient loss in the cone outer segment tip (COST) reflection followed by its
      return that is axially displaced anteriorly. Using this signature, we measured
      the temporal and spatial properties of shedding events in three normal subjects.
      Average duration of the shedding event was 8.8 +/- 13.4 minutes, and average
      length loss of the OS was 2.1 MUm (7.0% of OS length). Prevalence of cone
      shedding was highest in the morning (14.3%) followed by the afternoon (5.7%) and
      evening (4.0%), with load distributed across the imaged patch. To the best of our
      knowledge these are the first images of photoreceptor disc shedding in the living
      retina.

PMID- 27895997
TI  - Thermal therapy with magnetic nanoparticles for cell destruction.
AB  - In this article we suggest a new concept for cell destruction based upon
      manipulating magnetic nanoparticles (MNPs) by applying external, low frequency
      alternating magnetic field (AMF) that oscillates the particles, together with
      focused laser illumination. Assessment of temperature profiles in a head and neck
      squamous cell carcinoma sample showed that cells with MNPs, treated with AMF (3
      Hz, 300 mW) and laser irradiation (30 mW), reached 42 degrees C after 4.5 min, as
      opposed to cells treated with laser but without AMF. Moreover, a theoretical
      model was developed to assess the overall theoretical temperature rise, which was
      shown to be 50% lower than the experimental temperature. Furthermore, we found
      that the combination of laser irradiation and AMF decreased the number of live
      cells by ~50%. Thus, the concentrated assembly of laser heating with AMF-induced
      MNP oscillations leads to more rapid and efficient cell death. These results
      suggest that the manipulated MNP technique can serve as a superior agent for PTT,
      with improved cell death capabilities.

PMID- 27895996
TI  - Label-free fast 3D coherent imaging reveals pancreatic islet micro
      vascularization and dynamic blood flow.
AB  - In diabetes, pancreatic beta-cells play a key role. These cells are clustered
      within structures called islets of Langerhans inside the pancreas and produce
      insulin, which is directly secreted into the blood stream. The dense
      vascularization of islets of Langerhans is critical for maintaining a proper
      regulation of blood glucose homeostasis and is known to be affected from the
      early stage of diabetes. The deep localization of these islets inside the
      pancreas in the abdominal cavity renders their in vivo visualization a
      challenging task. A fast label-free imaging method with high spatial resolution
      is required to study the vascular network of islets of Langerhans. Based on these
      requirements, we developed a label-free and three-dimensional imaging method for
      observing islets of Langerhans using extended-focus Fourier domain Optical
      Coherence Microscopy (xfOCM). In addition to structural imaging, this system
      provides three-dimensional vascular network imaging and dynamic blood flow
      information within islets of Langerhans. We propose our method to deepen the
      understanding of the interconnection between diabetes and the evolution of the
      islet vascular network.

PMID- 27895998
TI  - Quantifying intraocular scatter with near diffraction-limited double-pass point
      spread function.
AB  - Measurement of the double-pass (DP) point-spread function (PSF) can provide an
      objective and non-invasive method for estimating intraocular scatter in the human
      eye. The objective scatter index (OSI), which is calculated from the DP PSF
      images, is commonly used to quantify intraocular scatter. In this article, we
      simulated the effect of higher-order ocular aberrations on OSI, and the results
      showed that higher-order ocular aberrations had a significant influence on OSI.
      Then we developed an adaptive optics DP PSF measurement system (AO-DPPMS) which
      was capable of correcting ocular aberrations up to eighth-order radial Zernike
      modes over a 6.0-mm pupil. Employing this system, we obtained DP PSF images of
      four subjects at the fovea. OSI values with aberrations corrected up to 2nd, 5th
      and 8th Zernike order were calculated respectively, from the DP PSF images of the
      four subjects. The experimental results were consistent with the simulation,
      suggesting that it is necessary to compensate for the higher-order ocular
      aberrations for accurate intraocular scatter estimation.

PMID- 27895999
TI  - Quantifying the effect of adipose tissue in muscle oximetry by near infrared
      spectroscopy.
AB  - Change of muscle tissue oxygen saturation (StO2), due to exercise, measured by
      near infrared spectroscopy (NIRS) is known to be lower for subjects with higher
      adipose tissue thickness. This is most likely not physiological but caused by the
      superficial fat and adipose tissue. In this paper we assessed, in vitro, the
      influence of adipose tissue thickness on muscle StO2, measured by NIRS oximeters.
      We measured StO2 of a liquid phantom by 3 continuous wave (CW) oximeters
      (Sensmart Model X-100 Universal Oximetry System, INVOS 5100C, and OxyPrem v1.3),
      as well as a frequency-domain oximeter, OxiplexTS, through superficial layers
      with 4 different thicknesses. Later, we employed the results to calibrate OxyPrem
      v1.3 for adipose tissue thickness in-vivo.

PMID- 27896000
TI  - Erratum: Perceived image quality with simulated segmented bifocal corrections:
      publisher's note.
AB  - [This corrects the article on p. 4388 in vol. 7.].

PMID- 27896001
TI  - Long-range, wide-field swept-source optical coherence tomography with GPU
      accelerated digital lock-in Doppler vibrography for real-time, in vivo middle ear
      diagnostics.
AB  - We present the design, implementation and validation of a swept-source optical
      coherence tomography (OCT) system for real-time imaging of the human middle ear
      in live patients. Our system consists of a highly phase-stable Vernier-tuned
      distributed Bragg-reflector laser along with a real-time processing engine
      implemented on a graphics processing unit. We use the system to demonstrate, for
      the first time in live subjects, real-time Doppler measurements of middle ear
      vibration in response to sound, video rate 2D B-mode imaging of the middle ear
      and 3D volumetric B-mode imaging. All measurements were performed non-invasively
      through the intact tympanic membrane demonstrating that the technology is readily
      translatable to the clinic.

PMID- 27896002
TI  - Erratum: Estimation of Jones matrix, birefringence and entropy using Cloude
      Pottier decomposition in polarization-sensitive optical coherence tomography:
      erratum.
AB  - [This corrects the article on p. 3551 in vol. 7, PMID: 27699120.].

PMID- 27896003
TI  - Kagome fiber based ultrafast laser microsurgery probe delivering micro-Joule
      pulse energies.
AB  - We present the development of a 5 mm, piezo-actuated, ultrafast laser scalpel for
      fast tissue microsurgery. Delivery of micro-Joules level energies to the tissue
      was made possible by a large, 31 MUm, air-cored inhibited-coupling Kagome fiber.
      We overcome the fiber's low NA by using lenses made of high refractive index ZnS,
      which produced an optimal focusing condition with 0.23 NA objective. The optical
      design achieved a focused laser spot size of 4.5 MUm diameter covering a 75 * 75
      MUm2 scan area in a miniaturized setting. The probe could deliver the maximum
      available laser power, achieving an average fluence of 7.8 J/cm2 on the tissue
      surface at 62% transmission efficiency. Such fluences could produce
      uninterrupted, 40 MUm deep cuts at translational speeds of up to 5 mm/s along the
      tissue. We predicted that the best combination of speed and coverage exists at 8
      mm/s for our conditions. The onset of nonlinear absorption in ZnS, however,
      limited the probe's energy delivery capabilities to 1.4 MUJ for linear operation
      at 1.5 picosecond pulse-widths of our fiber laser. Alternatives like broadband
      CaF2 crystals should mitigate such nonlinear limiting behavior. Improved opto
      mechanical design and appropriate material selection should allow substantially
      higher fluence delivery and propel such Kagome fiber-based scalpels towards
      clinical translation.

PMID- 27896004
TI  - Photolysis of a peptide with N-peptidyl-7-nitroindoline units using two-photon
      absorption.
AB  - N-acyl-7-nitroindolines have been used as caged compounds to photorelease active
      molecules by a one- or two-photon excitation mechanism in biological systems.
      Here, we report the photolysis of a polypeptide that contains 7-nitroindoline
      units as linker moieties in its peptide backbone for potential materials
      engineering applications. Upon two-photon excitation with femtosecond laser light
      at 710 nm the photoreactive amide bond in N-peptidyl-7-nitroindolines is cleaved
      rendering short peptide fragments. Thus, this photochemical process changes the
      molecular composition at the laser focal volume. Gel modifications of this
      peptide can potentially be used for three-dimensional microstructure fabrication.

PMID- 27896005
TI  - Cerebral blood flow is decoupled from blood pressure and linked to EEG bursting
      after resuscitation from cardiac arrest.
AB  - In the present study, we have developed a multi-modal instrument that combines
      laser speckle imaging, arterial blood pressure, and electroencephalography (EEG)
      to quantitatively assess cerebral blood flow (CBF), mean arterial pressure (MAP),
      and brain electrophysiology before, during, and after asphyxial cardiac arrest
      (CA) and resuscitation. Using the acquired data, we quantified the time and
      magnitude of the CBF hyperemic peak and stabilized hypoperfusion after
      resuscitation. Furthermore, we assessed the correlation between CBF and MAP
      before and after stabilized hypoperfusion. Finally, we examined when brain
      electrical activity resumes after resuscitation from CA with relation to CBF and
      MAP, and developed an empirical predictive model to predict when brain electrical
      activity resumes after resuscitation from CA. Our results show that: 1) more
      severe CA results in longer time to stabilized cerebral hypoperfusion; 2) CBF and
      MAP are coupled before stabilized hypoperfusion and uncoupled after stabilized
      hypoperfusion; 3) EEG activity (bursting) resumes after the CBF hyperemic phase
      and before stabilized hypoperfusion; 4) CBF predicts when EEG activity resumes
      for 5-min asphyxial CA, but is a poor predictor for 7-min asphyxial CA. Together,
      these novel findings highlight the importance of using multi-modal approaches to
      investigate CA recovery to better understand physiological processes and
      ultimately improve neurological outcome.

PMID- 27896006
TI  - Ultrahigh-speed, phase-sensitive full-field interferometric confocal microscopy
      for quantitative microscale physiology.
AB  - We developed ultra-high-speed, phase-sensitive, full-field reflection
      interferometric confocal microscopy (FFICM) for the quantitative characterization
      of in vivo microscale biological motions and flows. We demonstrated 2D frame
      rates in excess of 1 kHz and pixel throughput rates up to 125 MHz. These fast
      FFICM frame rates were enabled by the use of a low spatial coherence, high-power
      laser source. Specifically, we used a dense vertical cavity surface emitting
      laser (VCSEL) array that synthesized low spatial coherence light through a large
      number of narrowband, mutually-incoherent emitters. Off-axis interferometry
      enabled single-shot acquisition of the complex-valued interferometric signal. We
      characterized the system performance (~2 MUm lateral resolution, ~8 MUm axial
      gating depth) with a well-known target. We also demonstrated the use of this
      highly parallelized confocal microscopy platform for visualization and
      quantification of cilia-driven surface flows and cilia beat frequency in an
      important animal model (Xenopus embryos) with >1 kHz frame rate. Such frame rates
      are needed to see large changes in local flow velocity over small distance (high
      shear flow), in this case, local flow around a single ciliated cell. More
      generally, our results are an important demonstration of low-spatial coherence,
      high-power lasers in high-performance, quantitative biomedical imaging.

PMID- 27896007
TI  - In-vivo monitoring of tissue oxygen saturation in deep brain structures using a
      single fiber optical system.
AB  - We propose a single fiber optical system for monitoring tissue oxygen saturation
      (sO2) based on continuous-wave reflectance spectroscopy in the visible
      wavelengths. The system is designed for measurements in deep brain structures by
      stereotaxically implanting the 200 MUm-core fiber probe into the tissue of
      interest. Monte Carlo (MC) simulations were used to estimate the measurement
      tissue volume between 0.02-0.03 mm3. Experiments in an optical phantom indicated
      the system had a root mean squared error (RMSE) of 4.21% compared with a
      commercial fluorescence-based tissue oxygen partial pressure measuring system.
      Finally, we used the system for continuously monitoring tissue sO2 from a highly
      localized volume in anesthetized mice.

PMID- 27896008
TI  - Experimental results of full scattering profile from finger tissue-like phantom.
AB  - Human tissue is one of the most complex optical media since it is turbid and
      nonhomogeneous. We suggest a new optical method for sensing physiological tissue
      state, based on the collection of the ejected light at all exit angles, to
      receive the full scattering profile. We built a unique set-up for noninvasive
      encircled measurement. We use a laser, a photodetector and finger tissues
      mimicking phantoms presenting different optical properties. Our method reveals an
      isobaric point, which is independent of the optical properties. We compared the
      new finger tissues-like phantoms to others samples and found the linear
      dependence between the isobaric point's angle and the exact tissue geometry.
      These findings can be useful for biomedical applications such as non-invasive and
      simple diagnostic of the fingertip joint, ear lobe and pinched tissues.

PMID- 27896009
TI  - Nonlinear characterization of elasticity using quantitative optical coherence
      elastography.
AB  - Optical coherence elastography (OCE) has been used to perform mechanical
      characterization on biological tissue at the microscopic scale. In this work, we
      used quantitative optical coherence elastography (qOCE), a novel technology we
      recently developed, to study the nonlinear elastic behavior of biological tissue.
      The qOCE system had a fiber-optic probe to exert a compressive force to deform
      tissue under the tip of the probe. Using the space-division multiplexed optical
      coherence tomography (OCT) signal detected by a spectral domain OCT engine, we
      were able to simultaneously quantify the probe deformation that was proportional
      to the force applied, and to quantify the tissue deformation. In other words, our
      qOCE system allowed us to establish the relationship between mechanical stimulus
      and tissue response to characterize the stiffness of biological tissue. Most
      biological tissues have nonlinear elastic behavior, and the apparent stress
      strain relationship characterized by our qOCE system was nonlinear an extended
      range of strain, for a tissue-mimicking phantom as well as biological tissues.
      Our experimental results suggested that the quantification of force in OCE was
      critical for accurate characterization of tissue mechanical properties and the
      qOCE technique was capable of differentiating biological tissues based on the
      elasticity of tissue that is generally nonlinear.

PMID- 27896010
TI  - Freeze-thaw hysteresis effects in terahertz imaging of biomedical tissues.
AB  - There have recently been several studies published involving terahertz (THz)
      imaging of frozen biomedical samples. In this paper, we investigate the effects
      of the freeze-thaw cycle on THz properties of porcine muscle and fat samples. For
      ordinary freezing, there was a significant change in the THz properties after
      thawing for muscle tissue but not for fat tissue. However, if snap-freezing was
      combined with fast-thawing instead of ordinary freezing and ordinary thawing,
      then the freeze-thaw hysteresis was removed.

PMID- 27896012
TI  - Long-range and wide field of view optical coherence tomography for in vivo 3D
      imaging of large volume object based on akinetic programmable swept source.
AB  - Current optical coherence tomography (OCT) imaging suffers from short ranging
      distance and narrow imaging field of view (FOV). There is growing interest in
      searching for solutions to these limitations in order to expand further in vivo
      OCT applications. This paper describes a solution where we utilize an akinetic
      swept source for OCT implementation to enable ~10 cm ranging distance, associated
      with the use of a wide-angle camera lens in the sample arm to provide a FOV of
      ~20 x 20 cm2. The akinetic swept source operates at 1300 nm central wavelength
      with a bandwidth of 100 nm. We propose an adaptive calibration procedure to the
      programmable akinetic light source so that the sensitivity of the OCT system over
      ~10 cm ranging distance is substantially improved for imaging of large volume
      samples. We demonstrate the proposed swept source OCT system for in vivo imaging
      of entire human hands and faces with an unprecedented FOV (up to 400 cm2). The
      capability of large-volume OCT imaging with ultra-long ranging and ultra-wide FOV
      is expected to bring new opportunities for in vivo biomedical applications.

PMID- 27896011
TI  - Skin inhomogeneity as a source of error in remote PPG-imaging.
AB  - Remote photoplethysmography (rPPG) imaging is an optical technique to remotely
      assess the local cutaneous microcirculation. Despite its potential for enabling
      health-related applications, the current understanding of the outcome images/maps
      remains incomplete. In this paper, we present a model and supporting experiments
      confirming the contribution of skin inhomogeneity to the morphology of PPG
      waveforms. Since rPPG imagers rely on the complex inner-product operator and may
      combine multiple wavelengths, the derived phase measurements reflect
      morphological heterogeneity of PPG signals to a larger extent than propagation
      related phase differences. The influence of light penetration depth on PPG was
      observed and modeled on the green and red wavelengths at the hand region. We
      further show how our work contributes to understanding reproducibility issues in
      recent papers on pulse wave velocity (PWV) estimation.

PMID- 27896013
TI  - Using electron microscopy to calculate optical properties of biological samples.
AB  - The microscopic structural origins of optical properties in biological media are
      still not fully understood. Better understanding these origins can serve to
      improve the utility of existing techniques and facilitate the discovery of other
      novel techniques. We propose a novel analysis technique using electron microscopy
      (EM) to calculate optical properties of specific biological structures. This
      method is demonstrated with images of human epithelial colon cell nuclei. The
      spectrum of anisotropy factor g, the phase function and the shape factor D of the
      nuclei are calculated. The results show strong agreement with an independent
      study. This method provides a new way to extract the true phase function of
      biological samples and provides an independent validation for optical property
      measurement techniques.

PMID- 27896014
TI  - Single-frame rapid autofocusing for brightfield and fluorescence whole slide
      imaging.
AB  - A critical consideration for whole slide imaging (WSI) platform is to perform
      accurate autofocusing at high speed. Typical WSI systems acquire a z-stack of
      sample images and determine the best focal position by maximizing a figure of
      merit. This strategy, however, has suffered from several limitations, including
      low speed due to multiple image acquisitions, relatively low accuracy of focal
      plane estimation, short axial range for autofocusing, and difficulties in
      handling transparent samples. By exploring the autocorrelation property of the
      tissue sections, we report a novel single-frame autofocusing scheme to address
      the above challenges. In this approach, we place a two-pinhole-modulated camera
      at the epi-illumination arm. The captured image contains two copies of the sample
      separated by a certain distance. By identifying this distance, we can recover the
      defocus distance of the sample over a long z-range without z-scanning. To handle
      transparent samples, we set an offset distance to the autofocusing camera for
      generating out-of-focus contrast in the captured image. The single-frame nature
      of our scheme allows autofocusing even when the stage is in continuous motion. We
      demonstrate the use of the our autofocusing scheme for fluorescence WSI and
      quantify the focusing performance on 1550 different tissue tiles. The average
      autofocusing error is ~0.11 depth-of-field, 3 folds better than that of
      conventional methods. We report an autofocusing speed of 0.037 s per tile, which
      is much faster than that of conventional methods. The autofocusing range is ~80
      um, 8 folds longer than that of conventional methods. The reported scheme is able
      to solve the autofocusing challenges in WSI systems and may find applications in
      high-throughput brightfield/fluorescence WSI.

PMID- 27896015
TI  - Development of a multi-wavelength diffuse optical tomography system for early
      diagnosis of rheumatoid arthritis: simulation, phantoms and healthy human
      studies.
AB  - A multi-wavelength diffuse optical tomography (DOT) system has been developed to
      directly extract physiological information, such as total haemoglobin
      concentration, from tissue in human hand joints. Novel methods for 3D surface
      imaging and spectrally constrained image reconstruction are introduced and their
      potential application to imaging of rheumatoid arthritis is discussed. Results
      are presented from simulation studies as well as experiments using phantoms and
      data from imaging of three healthy volunteers. The image features are recovered
      partially for phantom data using transmission measurements only. Images that
      reveal joint regions and surrounding features within the hand are shown to co
      register with co-acquired ultrasound images which are shown to be related to
      total haemoglobin concentration.

PMID- 27896016
TI  - Wide-field Fourier ptychographic microscopy using laser illumination source.
AB  - Fourier ptychographic (FP) microscopy is a coherent imaging method that can
      synthesize an image with a higher bandwidth using multiple low-bandwidth images
      captured at different spatial frequency regions. The method's demand for multiple
      images drives the need for a brighter illumination scheme and a high-frame-rate
      camera for a faster acquisition. We report the use of a guided laser beam as an
      illumination source for an FP microscope. It uses a mirror array and a 2
      dimensional scanning Galvo mirror system to provide a sample with plane-wave
      illuminations at diverse incidence angles. The use of a laser presents speckles
      in the image capturing process due to reflections between glass surfaces in the
      system. They appear as slowly varying background fluctuations in the final
      reconstructed image. We are able to mitigate these artifacts by including a phase
      image obtained by differential phase contrast (DPC) deconvolution in the FP
      algorithm. We use a 1-Watt laser configured to provide a collimated beam with 150
      mW of power and beam diameter of 1 cm to allow for the total capturing time of
      0.96 seconds for 96 raw FPM input images in our system, with the camera sensor's
      frame rate being the bottleneck for speed. We demonstrate a factor of 4
      resolution improvement using a 0.1 NA objective lens over the full camera field
      of-view of 2.7 mm by 1.5 mm.

PMID- 27896017
TI  - Simple approach to three-color two-photon microscopy by a fiber-optic wavelength
      convertor.
AB  - A simple approach to multi-color two-photon microscopy of the red, green, and
      blue fluorescent indicators was reported based on an ultra-compact 1.03-MUm
      femtosecond laser and a nonlinear fiber. Inside the nonlinear fiber, the 1.03-MUm
      laser pulses were simultaneously blue-shifted to 0.6~0.8 MUm and red-shifted to
      1.2~1.4 MUm region by the Cherenkov radiation and fiber Raman gain effects. The
      wavelength-shifted 0.6~0.8 MUm and 1.2~1.4 MUm radiations were co-propagated with
      the residual non-converted 1.03-MUm pulses inside the same nonlinear fiber to
      form a fiber-output three-color femtosecond source. The application of the multi
      wavelength sources on multi-color two-photon fluorescence microscopy were also
      demonstrated. Overall, due to simple system configuration, convenient wavelength
      conversion, easy wavelength tunability within the entire 0.7~1.35 MUm bio
      penetration window and less requirement for high power and bulky light sources,
      the simple approach to multi-color two-photon microscopy could be widely
      applicable as an easily implemented and excellent research tool for future
      biomedical and possibly even clinical applications.

PMID- 27896018
TI  - Development and preliminary results of bimanual smart micro-surgical system using
      a ball-lens coupled OCT distance sensor.
AB  - Bimanual surgery enhances surgical effectiveness and is required to successfully
      accomplish complex microsurgical tasks. The essential advantage is the ability to
      simultaneously grasp tissue with one hand to provide counter traction or
      exposure, while dissecting with the other. Towards enhancing the precision and
      safety of bimanual microsurgery we present a bimanual SMART micro-surgical system
      for a preliminary ex-vivo study. To the best of our knowledge, this is the first
      demonstration of a handheld bimanual microsurgical system. The essential
      components include a ball-lens coupled common-path swept source optical coherence
      tomography sensor. This system effectively suppresses asynchronous hand tremor
      using two PZT motors in feedback control loop and efficiently assists
      ambidextrous tasks. It allows precise bimanual dissection of biological tissues
      with a reduction in operating time as compared to the same tasks performed with
      conventional one-handed approaches.

PMID- 27896019
TI  - Naloxone and Metabolites Quantification in Cord Blood of Prenatally Exposed
      Newborns and Correlations with Maternal Concentrations.
AB  - Objective To quantify naloxone and metabolite concentrations in newborns
      prenatally exposed to sublingual buprenorphine/naloxone and to correlate neonatal
      and maternal metabolite concentrations. Methods This is a prospective
      observational cohort study. Eleven pregnant women treated for opioid use disorder
      with sublingual buprenorphine/naloxone were enrolled. Maternal and newborn blood
      was collected and analyzed for naloxone, buprenorphine, and metabolites via
      liquid chromatography tandem mass spectrometry. Descriptive statistics and
      correlation coefficients were utilized to analyze data. Results Maternal daily
      naloxone and buprenorphine doses were 1 to 5 mg and 4 to 20 mg, respectively; the
      mean (standard deviation) time from medication until delivery was 9.9 (4.3)
      hours. Naloxone was below the limits of quantification (LOQ) in five infants and
      six mothers with a range of less than LOQ to 0.3 MUg/L. There was a strong
      positive correlation between maternal and newborn naloxone concentrations:
      Spearman's rho = 0.89 (p < 0.01). There were strong positive correlations between
      maternal and neonatal assays for the buprenorphine analyte concentrations:
      buprenorphine rho = 0.88 (p < 0.01), norbuprenorphine rho = 0.71 (p = 0.01), and
      norbuprenorphine-glucuronide rho = 0.98 (p < 0.01), but not for buprenorphine
      glucuronide, rho = 0.53 (p = 0.10). Conclusion Naloxone and buprenorphine are
      transferred to the fetus during prenatal exposure to maternal sublingual
      buprenorphine/naloxone. The quantity of naloxone transferred from maternal
      circulation is minimal and highly correlated with maternal concentrations.

PMID- 27896021
TI  - Lithocholic acid induces endoplasmic reticulum stress, autophagy and
      mitochondrial dysfunction in human prostate cancer cells.
AB  - Lithocholic acid (LCA) is a secondary bile acid that is selectively toxic to
      human neuroblastoma, breast and prostate cancer cells, whilst sparing normal
      cells. We previously reported that LCA inhibited cell viability and proliferation
      and induced apoptosis and necrosis of androgen-dependent LNCaP and androgen
      independent PC-3 human prostate cancer cells. In the present study, we
      investigated the roles of endoplasmic reticulum (ER) stress, autophagy and
      mitochondrial dysfunction in the toxicity of LCA in PC-3 and autophagy deficient,
      androgen-independent DU-145 cells. LCA induced ER stress-related proteins, such
      as CCAAT-enhancer-binding protein homologous protein (CHOP), and the
      phosphorylation of eukaryotic initiation factor 2-alpha (p-eIF2alpha) and c-Jun N
      terminal kinases (p-JNK) in both cancer cell-types. The p53 upregulated modulator
      of apoptosis (PUMA) and B cell lymphoma-like protein 11 (BIM) levels were
      decreased at overtly toxic LCA concentrations, although PUMA levels increased at
      lower LCA concentrations in both cell lines. LCA induced autophagy-related
      conversion of microtubule-associated proteins 1A/1B light chain 3B (LC3BI
      LC3BII), and autophagy-related protein ATG5 in PC-3 cells, but not in autophagy
      deficient DU-145 cells. LCA (>10 uM) increased levels of reactive oxygen species
      (ROS) concentration-dependently in PC-3 cells, whereas ROS levels were not
      affected in DU-145 cells. Salubrinal, an inhibitor of eIF2alpha dephosphorylation
      and ER stress, reduced LCA-induced CHOP levels slightly in PC-3, but not DU-145
      cells. Salubrinal pre-treatment increased the cytotoxicity of LCA in PC-3 and DU
      145 cells and resulted in a statistically significant loss of cell viability at
      normally non-toxic concentrations of LCA. The late-stage autophagy inhibitor
      bafilomycin A1 exacerbated LCA toxicity at subtoxic LCA concentrations in PC-3
      cells. The antioxidant alpha-tocotrienol strongly inhibited the toxicity of LCA
      in PC-3 cells, but not in DU-145 cells. Collectively, although LCA induces
      autophagy and ER stress in PC-3 cells, these processes appear to be initially of
      protective nature and subsequently consequential to, but not critical for the ROS
      mediated mitochondrial dysfunction and cytotoxicity of LCA. The full mechanism of
      LCA-induced mitochondrial dysfunction and cytotoxicity in the similarly sensitive
      DU-145 cells remains to be elucidated.

PMID- 27896022
TI  - PDIA3 gene induces visceral hypersensitivity in rats with irritable bowel
      syndrome through the dendritic cell-mediated activation of T cells.
AB  - This study investigated the mechanism of protein disulfide-isomerase A3 (PDIA3)
      induced visceral hypersensitivity in irritable bowel syndrome (IBS). Rats were
      treated with saline (control), acetic acid and restraint stress (IBS model),
      empty vector (RNAi control) and PDIA3-RNAi vector (PDIA3-RNAi). Mesenteric lymph
      node DCs (MLNDCs) and splenic CD4+/CD8+ T cells were isolated for co-cultivation.
      Compared with control, MLNDCs co-cultured with CD4+ or CD8+ T cells showed an
      increased ability to promote T cell proliferation and produced more IL-4 or IL-9
      secretion. Compared with the RNAi control, MLNDCs from the PDIA3 knockdown models
      were less effective in promoting the proliferation of CD4+/CD8+ T cells. It is
      concluded that PDIA3 plays an important role in the development of IBS through
      the DC-mediated activation of T cells, resulting in degranulation of MCs and
      visceral hypersensitivity.

PMID- 27896020
TI  - Identification of phenolic secondary metabolites from Schotia brachypetala Sond.
      (Fabaceae) and demonstration of their antioxidant activities in Caenorhabditis
      elegans.
AB  - BACKGROUND: Schotia brachypetala Sond. (Fabaceae) is an endemic tree of Southern
      Africa whose phytochemistry and pharmacology were slightly studied. The present
      work aimed at profiling the major phenolics compounds present in the hydro
      alcohol extract from S. brachypetala leaves (SBE) using LC/HRESI/MS/MS and NMR
      and prove their antioxidant capabilities using novel methods. METHODS: In vitro
      assays; DPPH, TEAC persulfate decolorizing kinetic and FRAP assays, and in vivo
      assays: Caenorhabditis elegans strains maintenance, Intracellular ROS in C.
      elegans, Survival assay, GFP expression and Subcellular DAF-16 localization were
      employed to evaluate the antioxidant activity. RESULTS: More than forty
      polyphenols, including flavonoid glycosides, galloylated flavonoid glycosides,
      isoflavones, dihydrochalcones, procyanidins, anthocyanins, hydroxy benzoic acid
      derivatives, hydrolysable tannins, and traces of methylated and acetylated
      flavonoid derivatives were identified. Three compounds were isolated and
      identified from the genus Schotia for the first time, namely gallic acid,
      myricetin-3-O-alpha-L-1C4-rhamnoside and quercetin-3-O-L-1C4-rhamnoside. The
      total phenolics content of SBE was (376 mg CAE/g), followed by flavonoids (67.87
      QE/g). In vitro antioxidant activity of SBE was evidenced by DPPH radical
      scavenging activity (IC50 of 9 ug/mL), FRAP ferric reducing activity (5,000 mol
      Fe2+ E/mg) and ABTS peroxide inhibiting activity (1,054 mM Trolox E/mg). The
      tested extract was able to protect the worms against juglone induced oxidative
      stress, an increased survival rate (up to 41%) was recorded, when compared with
      the control group (11%) and attenuate the reactive oxygen species (ROS)
      accumulation in dose-dependent and reached up to 72% for the highest tested
      concentration. SBE was also able to attenuate the levels of heat shock protein
      (HSP) expression in dose-dependent up to 60% in the 150 ug SBE/mL group. In DAF
      16 Subcellular localization SBE treated worms showed nuclear localization pattern
      up to 78%, while it was only 5% in the untreated control group. DISCUSSION: A
      pronounced antioxidant activity in vivo, which can be attributed to its ability
      to promote the nuclear translocation of DAF-16/FOXO, the main transcription
      factor regulating the expression of stress response genes. The remarkable
      antioxidant activity in vitro and in vivo correlates to SBE rich phenolic
      profile.

PMID- 27896023
TI  - Ceratopogonidae (Diptera: Nematocera) of the piedmont of the Yungas forests of
      Tucuman: ecology and distribution.
AB  - Within the Ceratopogonidae family, many genera transmit numerous diseases to
      humans and animals, while others are important pollinators of tropical crops. In
      the Yungas ecoregion of Argentina, previous systematic and ecological research on
      Ceratopogonidae focused on Culicoides, since they are the main transmitters of
      mansonelliasis in northwestern Argentina; however, few studies included the
      genera Forcipomyia, Dasyhelea, Atrichopogon, Alluaudomyia, Echinohelea, and
      Bezzia. Therefore, the objective of this study was to determine the presence and
      abundance of Ceratopogonidae in this region, their association with
      meteorological variables, and their variation in areas disturbed by human
      activity. Monthly collection of specimens was performed from July 2008 to July
      2009 using CDC miniature light traps deployed for two consecutive days. A total
      of 360 specimens were collected, being the most abundant Dasyhelea genus (48.06%)
      followed by Forcipomyia (26.94%) and Atrichopogon (13.61%). Bivariate analyses
      showed significant differences in the abundance of the genera at different
      sampling sites and climatic conditions, with the summer season and El Corralito
      site showing the greatest abundance of specimens. Accumulated rainfall was the
      variable that related the most to the abundance of Culicoides (10.56%), while
      temperature was the most closely related variable to the abundance of
      Forcipomyia, Dasyhelea, and Atrichopogon.

PMID- 27896024
TI  - Salinity modulates thermotolerance, energy metabolism and stress response in
      amphipods Gammarus lacustris.
AB  - Temperature and salinity are important abiotic factors for aquatic invertebrates.
      We investigated the influence of different salinity regimes on thermotolerance,
      energy metabolism and cellular stress defense mechanisms in amphipods Gammarus
      lacustris Sars from two populations. We exposed amphipods to different thermal
      scenarios and determined their survival as well as activity of major antioxidant
      enzymes (peroxidase, catalase, glutathione S-transferase) and parameters of
      energy metabolism (content of glucose, glycogen, ATP, ADP, AMP and lactate).
      Amphipods from a freshwater population were more sensitive to the thermal
      challenge, showing higher mortality during acute and gradual temperature change
      compared to their counterparts from a saline lake. A more thermotolerant
      population from a saline lake had high activity of antioxidant enzymes. The
      energy limitations of the freshwater population (indicated by low baseline
      glucose levels, downward shift of the critical temperature of aerobic metabolism
      and inability to maintain steady-state ATP levels during warming) was observed,
      possibly reflecting a trade-off between the energy demands for osmoregulation
      under the hypo-osmotic condition of a freshwater environment and protection
      against temperature stress.

PMID- 27896025
TI  - Zebra mussel beds: an effective feeding ground for Ponto-Caspian gobies or
      suitable shelter for their prey?
AB  - Aggregations of the Ponto-Caspian invasive zebra mussel (Dreissena polymorpha)
      constitute a suitable habitat for macroinvertebrates, considerably increasing
      their abundance and providing effective antipredator protection. Thus, the
      overall effect of a mussel bed on particular predator species may vary from
      positive to negative, depending on both prey density increase and predator
      ability to prey in a structurally complex habitat. Alien Ponto-Caspian goby fish
      are likely to be facilitated when introduced into new areas by zebra mussels,
      provided that they are capable of utilizing mussel beds as habitat and feeding
      grounds. We ran laboratory experiments to find which prey (chironomid larvae)
      densities (from ca. 500 to 2,000 individuals m-2) in a mussel bed make it a more
      beneficial feeding ground for the racer goby Babka gymnotrachelus (RG) and
      western tubenose goby Proterorhinus semilunaris (WTG) compared to sandy and stone
      substrata (containing the basic prey density of 500 ind. m-2). Moreover, we
      checked how food availability affects habitat selection by fish. Mussel beds
      became more suitable for fish than alternative mineral substrata when food
      abundance was at least two times higher (1,000 vs. 500 ind. m-2), regardless of
      fish size and species. WTG was associated with mussel beds regardless of its size
      and prey density, whereas RG switched to this habitat when it became a better
      feeding ground than alternative substrata. Larger RG exhibited a stronger
      affinity for mussels than small individuals. WTG fed more efficiently from a
      mussel bed at high food abundances than RG. A literature review has shown that
      increasing chironomid density, which in our study was sufficient to make a mussel
      habitat an attractive feeding ground for the gobies, is commonly observed in
      mussel beds in the field. Therefore, we conclude that zebra mussels may
      positively affect the alien goby species and are likely to facilitate their
      establishment in novel areas, contributing to an invasional meltdown in the Ponto
      Caspian invasive community.

PMID- 27896026
TI  - jicbioimage: a tool for automated and reproducible bioimage analysis.
AB  - There has been steady improvement in methods for capturing bioimages. However
      analysing these images still remains a challenge. The Python programming language
      provides a powerful and flexible environment for scientific computation. It has a
      wide range of supporting libraries for image processing but lacks native support
      for common bioimage formats, and requires specific code to be written to ensure
      that suitable audit trails are generated and analyses are reproducible. Here we
      describe the development of a Python tool that: (1) allows users to quickly view
      and explore microscopy data; (2) generate reproducible analyses, encoding a
      complete history of image transformations from raw data to final result; and (3)
      scale up analyses from initial exploration to high throughput processing
      pipelines, with a minimal amount of extra effort. The tool, jicbioimage, is open
      source and freely available online at http://jicbioimage.readthedocs.io.

PMID- 27896027
TI  - Assessing pollinators' use of floral resource subsidies in agri-environment
      schemes: An illustration using Phacelia tanacetifolia and honeybees.
AB  - BACKGROUND: Honeybees (Apis mellifera L.) are frequently used in agriculture for
      pollination services because of their abundance, generalist floral preferences,
      ease of management and hive transport. However, their populations are declining
      in many countries. Agri-Environment Schemes (AES) are being implemented in
      agricultural systems to combat the decline in populations of pollinators and
      other insects. Despite AES being increasingly embedded in policy and budgets,
      scientific assessments of many of these schemes still are lacking, and only a few
      studies have examined the extent to which insect pollinators use the floral
      enhancements that are part of AES and on which floral components they feed (i.e.,
      pollen and/or nectar). METHODS: In the present work, we used a combination of
      observations on honeybee foraging for nectar/pollen from the Californian annual
      plant Phacelia tanacetifolia in the field, collection of pollen pellets from
      hives, and pollen identification, to assess the value of adding phacelia to an
      agro-ecosystem to benefit honeybees. RESULTS: It was found that phacelia pollen
      was almost never taken by honeybees. The work here demonstrates that honeybees
      may not use the floral enhancements added to a landscape as expected and points
      to the need for more careful assessments of what resources are used by honeybees
      in AES and understanding the role, if any, which AES play in enhancing pollinator
      fitness. DISCUSSION: We recommend using the methodology in this paper to explore
      the efficacy of AES before particular flowering species are adopted more widely
      to give a more complete illustration of the actual efficacy of AES.

PMID- 27896029
TI  - Biology of tiny animals: three new species of minute salamanders (Plethodontidae:
      Thorius) from Oaxaca, Mexico.
AB  - We describe three new species of minute salamanders, genus Thorius, from the
      Sierra Madre del Sur of Oaxaca, Mexico. Until now only a single species, T.
      minutissimus, has been reported from this region, although molecular data have
      long shown extensive genetic differentiation among geographically disjunct
      populations. Adult Thorius pinicola sp. nov., T. longicaudus sp. nov., and T.
      tlaxiacus sp. nov. are larger than T. minutissimus and possess elliptical rather
      than oval nostrils; T. pinicola and T. longicaudus also have longer tails. All
      three new species occur west of the range of T. minutissimus, which has the
      easternmost distribution of any member of the genus. The new species are
      distinguished from each other and from other named Thorius in Oaxaca by a
      combination of adult body size, external morphology and osteology, and by protein
      characters (allozymes) and differences in DNA sequences. In addition, we
      redescribe T. minutissimus and a related species, T. narisovalis, to further
      clarify the taxonomic status of Oaxacan populations and to facilitate future
      studies of the remaining genetically differentiated Thorius that cannot be
      satisfactorily assigned to any named species. Populations of all five species
      considered here appear to have declined dramatically over the last one or two
      decades and live specimens are difficult to find in nature. Thorius may be the
      most endangered genus of amphibians in the world. All species may go extinct
      before the end of this century.

PMID- 27896028
TI  - The scavenger receptor repertoire in six cnidarian species and its putative role
      in cnidarian-dinoflagellate symbiosis.
AB  - Many cnidarians engage in a mutualism with endosymbiotic photosynthetic
      dinoflagellates that forms the basis of the coral reef ecosystem. Interpartner
      interaction and regulation includes involvement of the host innate immune system.
      Basal metazoans, including cnidarians have diverse and complex innate immune
      repertoires that are just beginning to be described. Scavenger receptors (SR) are
      a diverse superfamily of innate immunity genes that recognize a broad array of
      microbial ligands and participate in phagocytosis of invading microbes. The
      superfamily includes subclades named SR-A through SR-I that are categorized based
      on the arrangement of sequence domains including the scavenger receptor cysteine
      rich (SRCR), the C-type lectin (CTLD) and the CD36 domains. Previous functional
      and gene expression studies on cnidarian-dinoflagellate symbiosis have implicated
      SR-like proteins in interpartner communication and regulation. In this study, we
      characterized the SR repertoire from a combination of genomic and transcriptomic
      resources from six cnidarian species in the Class Anthozoa. We combined these
      bioinformatic analyses with functional experiments using the SR inhibitor
      fucoidan to explore a role for SRs in cnidarian symbiosis and immunity.
      Bioinformatic searches revealed a large diversity of SR-like genes that resembled
      SR-As, SR-Bs, SR-Es and SR-Is. SRCRs, CTLDs and CD36 domains were identified in
      multiple sequences in combinations that were highly homologous to vertebrate SRs
      as well as in proteins with novel domain combinations. Phylogenetic analyses of
      CD36 domains of the SR-B-like sequences from a diversity of metazoans grouped
      cnidarian with bilaterian sequences separate from other basal metazoans. All
      cnidarian sequences grouped together with moderate support in a subclade
      separately from bilaterian sequences. Functional experiments were carried out on
      the sea anemone Aiptasia pallida that engages in a symbiosis with Symbiodinium
      minutum (clade B1). Experimental blocking of the SR ligand binding site with the
      inhibitor fucoidan reduced the ability of S. minutum to colonize A. pallida
      suggesting that host SRs play a role in host-symbiont recognition. In addition,
      incubation of symbiotic anemones with fucoidan elicited an immune response,
      indicating that host SRs function in immune modulation that results in host
      tolerance of the symbionts.

PMID- 27896031
TI  - Salinity and temperature significantly influence seed germination, seedling
      establishment, and seedling growth of eelgrass Zostera marina L.
AB  - Globally, seagrass beds have been recognized as critical yet declining coastal
      habitats. To mitigate seagrass losses, seagrass restorations have been conducted
      in worldwide over the past two decades. Seed utilization is considered to be an
      important approach in seagrass restoration efforts. In this study, we
      investigated the effects of salinity and temperature on seed germination,
      seedling establishment, and seedling growth of eelgrass Zostera marina L. (Swan
      Lake, northern China). We initially tested the effects of salinity (0, 5, 10, 15,
      20, 25, 30, 35, and 40 ppt) and water temperature (5, 10, 15, and 20  degrees C)
      on seed germination to identify optimal levels. To identify levels of salinity
      that could potentially limit survival and growth, and, consequently, the spatial
      distribution of seedlings in temperate estuaries, we then examined the effect of
      freshwater and other salinity levels (10, 20, and 30 ppt) on seedling growth and
      establishment to confirm suitable conditions for seedling development. Finally,
      we examined the effect of transferring germinated seeds from freshwater or low
      salinity levels (1, 5, and 15 ppt) to natural seawater (32 ppt) on seedling
      establishment rate (SER) at 15  degrees C. In our research, we found that: (1)
      Mature seeds had a considerably lower moisture content than immature seeds;
      therefore, moisture content may be a potential indicator of Z. marina seed
      maturity; (2) Seed germination significantly increased at low salinity (p <
      0.001) and high temperature (p < 0.001). Salinity had a much stronger influence
      on seed germination than temperature. Maximum seed germination (88.67 +/- 5.77%)
      was recorded in freshwater at 15  degrees C; (3) Freshwater and low salinity
      levels (< 20 ppt) increased germination but had a strong negative effect on
      seedling morphology (number of leaves per seedling reduced from 2 to 0, and
      maximum seedling leaf length reduced from 4.48 to 0 cm) and growth (seedling
      biomass reduced by 46.15-66.67% and maximum seedling length reduced by 21.16
      69.50%). However, Z. marina performed almost equally well at salinities of 20 and
      30 ppt. Very few germinated seeds completed leaf differentiation and seedling
      establishment in freshwater or at low salinity, implying that freshwater and low
      salinity may potentially limit the distribution of this species in coastal and
      estuarine waters. Therefore, the optimum salinity for Z. marina seedling
      establishment and colonization appears to be above 20 ppt in natural beds; (4)
      Seeds germinated in freshwater or at low salinity levels could be transferred to
      natural seawater to accomplish seedling establishment and colonization. This may
      be the optimal method for the adoption of seed utilization in seagrass
      restoration. We also identified seven stages of seed germination and seedling
      metamorphosis in order to characterize growth and developmental characteristics.
      Our results may serve as useful information for Z. marina habitat establishment
      and restoration programs.

PMID- 27896030
TI  - Historical reconstruction of climatic and elevation preferences and the evolution
      of cloud forest-adapted tree ferns in Mesoamerica.
AB  - BACKGROUND: Cloud forests, characterized by a persistent, frequent or seasonal
      low-level cloud cover and fragmented distribution, are one of the most threatened
      habitats, especially in the Neotropics. Tree ferns are among the most conspicuous
      elements in these forests, and ferns are restricted to regions in which minimum
      temperatures rarely drop below freezing and rainfall is high and evenly
      distributed around the year. Current phylogeographic data suggest that some of
      the cloud forest-adapted species remained in situ or expanded to the lowlands
      during glacial cycles and contracted allopatrically during the interglacials.
      Although the observed genetic signals of population size changes of cloud forest
      adapted species including tree ferns correspond to predicted changes by
      Pleistocene climate change dynamics, the observed patterns of intraspecific
      lineage divergence showed temporal incongruence. METHODS: Here we combined
      phylogenetic analyses, ancestral area reconstruction, and divergence time
      estimates with climatic and altitudinal data (environmental space) for phenotypic
      traits of tree fern species to make inferences about evolutionary processes in
      deep time. We used phylogenetic Bayesian inference and geographic and altitudinal
      distribution of tree ferns to investigate ancestral area and elevation and
      environmental preferences of Mesoamerican tree ferns. The phylogeny was then used
      to estimate divergence times and ask whether the ancestral area and elevation and
      environmental shifts were linked to climatic events and historical climatic
      preferences. RESULTS: Bayesian trees retrieved Cyathea, Alsophyla, Gymnosphaera
      and Sphaeropteris in monophyletic clades. Splits for species in these genera
      found in Mesoamerican cloud forests are recent, from the Neogene to the
      Quaternary, Australia was identified as the ancestral area for the clades of
      these genera, except for Gymnosphaera that was Mesoamerica. Climate tolerance was
      not divergent from hypothesized ancestors for the most significant variables or
      elevation. For elevational shifts, we found repeated change from low to high
      elevations. CONCLUSIONS: Our data suggest that representatives of Cyatheaceae
      main lineages migrated from Australia to Mesoamerican cloud forests in different
      times and have persisted in these environmentally unstable areas but extant
      species diverged recentrly from their ancestors.

PMID- 27896032
TI  - Gene expression profile of sodium channel subunits in the anterior cingulate
      cortex during experimental paclitaxel-induced neuropathic pain in mice.
AB  - Paclitaxel, a chemotherapeutic agent, causes neuropathic pain whose supraspinal
      pathophysiology is not fully understood. Dysregulation of sodium channel
      expression, studied mainly in the periphery and spinal cord level, contributes to
      the pathogenesis of neuropathic pain. We examined gene expression of sodium
      channel (Nav) subunits by real time polymerase chain reaction (PCR) in the
      anterior cingulate cortex (ACC) at day 7 post first administration of paclitaxel,
      when mice had developed paclitaxel-induced thermal hyperalgesia. The ACC was
      chosen because increased activity in the ACC has been observed during neuropathic
      pain. In the ACC of vehicle-treated animals the threshold cycle (Ct) values for
      Nav1.4, Nav1.5, Nav1.7, Nav1.8 and Nav1.9 were above 30 and/or not detectable in
      some samples. Thus, comparison in mRNA expression between untreated control,
      vehicle-treated and paclitaxel treated animals was done for Nav1.1, Nav1.2,
      Nav1.3, Nav1.6, Nax as well as Navbeta1-Navbeta4. There were no differences in
      the transcript levels of Nav1.1-Nav1.3, Nav1.6, Nax, Navbeta1-Navbeta3 between
      untreated and vehicle-treated mice, however, vehicle treatment increased Navbeta4
      expression. Paclitaxel treatment significantly increased the mRNA expression of
      Nav1.1, Nav1.2, Nav1.6 and Nax, but not Nav1.3, sodium channel alpha subunits
      compared to vehicle-treated animals. Treatment with paclitaxel significantly
      increased the expression of Navbeta1 and Navbeta3, but not Navbeta2 and Navbeta4,
      sodium channel beta subunits compared to vehicle-treated animals. These findings
      suggest that during paclitaxel-induced neuropathic pain (PINP) there is
      differential upregulation of sodium channels in the ACC, which might contribute
      to the increased neuronal activity observed in the area during neuropathic pain.

PMID- 27896033
TI  - Multiple, independent colonizations of the Hawaiian Archipelago by the family
      Dolichopodidae (Diptera).
AB  - The family Dolichopodidae forms two of the four largest evolutionary radiations
      in the Hawaiian Islands across all flies: Campsicnemus (183 spp) and the
      Eurynogaster complex (66 spp). They also include a small radiation of Conchopus
      (6 spp). A handful of other dolichopodid species are native to the islands in
      singleton lineages or small radiations. This study provides a phylogenetic
      perspective on the colonization history of the dolichopodid fauna in the islands.
      We generated a multi-gene data set including representatives from 11 of the 14
      endemic Hawaiian dolichopodid genera to examine the history of colonization to
      the islands, and analyzed it using Bayesian and maximum likelihood phylogenetic
      methods. We used a subset of the data that included Conchopus and the eight
      genera comprising the Eurynogaster complex to estimate the first phylogenetic
      hypothesis for these endemic groups, then used Beast to estimate their age of
      arrival to the archipelago. The Eurynogaster complex, Campsicnemus and Conchopus
      are clearly the result of independent colonizations. The results strongly support
      the Eurynogaster complex as a monophyletic group, and also supports the monophyly
      of 4 of the 8 described genera within the complex (Adachia, Arciellia, Uropachys
      and Eurynogaster). Members of the family Dolichopodidae have been dispersing over
      vast distances to colonize the Hawaiian Archipelago for millions of years,
      leading to multiple independent evolutionary diversification events. The
      Eurynogaster complex arrived in the Hawaiian Archipelago 11.8 Ma, well before the
      arrival of Campsicnemus (4.5 Ma), and the even more recent Conchopus (1.8 Ma).
      Data presented here demonstrate that the Hawaiian Dolichopodidae both disperse
      and diversify easily, a rare combination that lays the groundwork for field
      studies on the reproductive isolating mechanisms and ecological partitioning of
      this group.

PMID- 27896035
TI  - A large scale test of the gaming-enhancement hypothesis.
AB  - A growing research literature suggests that regular electronic game play and game
      based training programs may confer practically significant benefits to cognitive
      functioning. Most evidence supporting this idea, the gaming-enhancement
      hypothesis, has been collected in small-scale studies of university students and
      older adults. This research investigated the hypothesis in a general way with a
      large sample of 1,847 school-aged children. Our aim was to examine the relations
      between young people's gaming experiences and an objective test of reasoning
      performance. Using a Bayesian hypothesis testing approach, evidence for the
      gaming-enhancement and null hypotheses were compared. Results provided no
      substantive evidence supporting the idea that having preference for or regularly
      playing commercially available games was positively associated with reasoning
      ability. Evidence ranged from equivocal to very strong in support for the null
      hypothesis over what was predicted. The discussion focuses on the value of
      Bayesian hypothesis testing for investigating electronic gaming effects, the
      importance of open science practices, and pre-registered designs to improve the
      quality of future work.

PMID- 27896034
TI  - Ficolin-2 inhibitors are present in sera after prolonged storage at -80  degrees
      C.
AB  - Ficolins can activate the lectin pathway of the complement system that provides
      innate immune protection against pathogens, marks host cellular debris for
      clearance, and promotes inflammation. Baseline inflammation increases with aging
      in a phenomenon known as "inflammaging." Although IL-6 and C-reactive protein are
      known to increase with age, contributions of many complement factors, including
      ficolins, to inflammaging have been little studied. Ficolin-2 is abundant in
      human serum and can recognize many target structures; therefore, ficolin-2 has
      potential to contribute to inflammaging. We hypothesized that inflammaging would
      alter ficolin-2 levels among older adults and examined 360 archived sera
      collected from older individuals. We found that these sera had apparently reduced
      ficolin-2 levels and that 84.2% of archived sera exhibited ficolin-2 inhibitors,
      which suppressed apparent amounts of ficolin-2 detected by enzyme-linked
      immunosorbent assay. Fresh serum samples were obtained from donors whose archived
      sera showed inhibitors, but the fresh sera did not have ficolin-2 inhibitors.
      Ficolin-2 inhibitors were present in other long-stored sera from younger persons.
      Furthermore, noninhibiting samples and fresh sera from older adults had
      apparently normal amounts of ficolin-2. Thus, ficolin-2 inhibitors may arise as
      an artifact of long-term storage of serum at -80  degrees C.

PMID- 27896036
TI  - Detecting sedimentation impacts to coral reefs resulting from dredging the Port
      of Miami, Florida USA.
AB  - The federal channel at Port of Miami, Florida, USA, was dredged between late 2013
      and early 2015 to widen and deepen the channel. Due to the limited spatial extent
      of impact-assessment monitoring associated with the project, the extent of the
      dredging impacts on surrounding coral reefs has not been well quantified.
      Previously published remote sensing analyses, as well as agency and anecdotal
      reports suggest the most severe and largest area of sedimentation occurred on a
      coral reef feature referred to as the Inner Reef, particularly in the sector
      north of the channel. A confounding regional warm-water mass bleaching event
      followed by a coral disease outbreak during this same time frame made the
      assessment of dredging-related impacts to coral reefs adjacent to the federal
      channel difficult but still feasible. The current study sought to better
      understand the sedimentation impacts that occurred in the coral reef environment
      surrounding Port of Miami, to distinguish those impacts from other regional
      events or disturbances, and provide supplemental information on impact assessment
      that will inform discussions on compensatory mitigation requirements. To this
      end, in-water field assessments conducted after the completion of dredging and a
      time series analysis of tagged corals photographed pre-, during, and post
      dredging, are used to discern dredging-related sedimentation impacts for the
      Inner Reef north. Results indicate increased sediment accumulation, severe in
      certain times and places, and an associated biological response (e.g., higher
      prevalence of partial mortality of corals) extended up to 700 m from the channel,
      whereas project-associated monitoring was limited to 50 m from the channel. These
      results can contribute to more realistic prediction of areas of indirect effect
      from dredging projects needed to accurately evaluate proposed projects and design
      appropriate compliance monitoring. Dredging projects near valuable and sensitive
      habitats subject to local and global stressors require monitoring methods capable
      of discerning non-dredging related impacts and adaptive management to ensure
      predicted and unpredicted project-related impacts are quantified. Anticipated
      increasing frequency and intensity of seasonal warming stress also suggests that
      manageable- but- unavoidable local stressors such as dredging should be
      partitioned from such seasonal thermal stress events.

PMID- 27896037
TI  - Functional Evaluation of Patients Undergoing Multiple Joint Replacements: A
      Retrospective Study of 50 Patients with a Minimum of Six Months of Follow-up.
AB  - INTRODUCTION:  Polyarthritis is a challenging condition that an orthopedic
      surgeon faces in day-to-day practice. Some of the conditions where multiple
      joints are affected are rheumatoid arthritis, osteoarthritis, and ankylosing
      spondylitis. Multiple joint afflictions can cause severe impairment in the
      quality of life, which leads to a significant socioeconomic burden on the family
      and society. Joint replacement is considered as a treatment when severe joint
      pain or dysfunction is not alleviated by conservative management. Total joint
      arthroplasty remains one of the most commonly performed and universally accepted
      operative interventions for such patients. MATERIALS AND METHODS:  Fifty patients
      were invited into the study. All patients included in the study were 18 years of
      age and older and had undergone two or more joint replacements with a minimum of
      six months duration from the last surgery. The data was collected during the
      preoperative and postoperative periods through patient records and
      questionnaires. The Short Form 36 Health Survey Questionnaire (SF-36) scores were
      generated from an online application that is readily available on the official
      website SF-36 scoring system. The results were compared, analyzed, and tested for
      significance using the Wilcoxon signed rank test. RESULTS:  The highest incidence
      of multiple joint replacements appears to be in the age-group of 51 - 70 years
      (52%), the mean age of patients being 51.7 +/- 14.4 years. The ratio of female to
      male patients was 1.6:1. On comparison of preoperative and postoperative (six
      months) physical component and mental component scores, the differences were
      found to be significant (p-value: < 0.01). This finding is irrespective of the
      diagnosis, gender, or age of the patient. CONCLUSION:  In the study conducted on
      50 patients, we found out that multiple joint arthroplasties are fruitful
      surgeries. The procedures are efficient in reducing the disabilities seen in
      patients with polyarthritis of various causes and improving the overall quality
      of life. We strongly recommend multiple joint arthroplasties to patients with
      severe disability. However, adequate medical management plays an equally
      important role to improve the overall results. Well-designed and larger studies
      are required to establish the treatment protocols and order of surgeries in
      patients with differing causes of polyarthritis.

PMID- 27896038
TI  - Focal Seizures Induced by Intracranial Electroencephalogram Grids.
AB  - Here we present a unique, but important seizure variant directly related to
      placement of subdural grids. Two distinct epileptogenic zones were identified,
      one which correlated with the patient's baseline seizures and a separate zone
      associated with atypical semiology and localization. Inspection of this zone at
      surgery revealed cortical deformation from the grid itself. The patient underwent
      successful surgical resection of the primary epileptogenic zone, but not that of
      the atypical zone. She remains seizure free at two years following surgery.
      Recognition of grid-induced seizures is important as they may confound the
      interpretation of intracranial electroencephalograms (iEEG) and mislead resective
      surgery.

PMID- 27896039
TI  - The Association between Alcohol and Sexual Risk Behaviors among College Students:
      A Review.
AB  - PURPOSE OF REVIEW: Alcohol use is prevalent among college students and may
      contribute to sexual risk behavior engagement. A narrative review of the recent
      empirical literature examining the association between alcohol use and sexual
      risk behaviors among college student samples was conducted. The purpose of this
      review was to: (a) review studies examining the association between alcohol use
      and risky sexual behaviors; and (b) overview research investigating alcohol
      expectancies and partner characteristics as factors that may influence the
      alcohol-risky sex relation among college students. RECENT FINDINGS: Findings
      regarding the direct link between alcohol use and sexual risk behaviors were
      mixed. Results suggest a more nuanced association between alcohol and risky
      sexual behaviors that is influenced by alcohol expectancies and partner
      characteristics. SUMMARY: Results highlight the importance of considering
      additional factors that may influence the alcohol-risky sex relation. Future
      interventions targeting alcohol-related sexual risk behavior engagement among
      college students are needed.

PMID- 27896040
TI  - Antibody-mediated Rejection in Lung Transplantation.
AB  - There has been increasing awareness of antibody-mediated rejection (AMR) as an
      important cause of graft failure after lung transplantation in recent years.
      However, the diagnostic criteria for pulmonary AMR are not well defined. All four
      tenets of AMR in kidney and heart transplantation, graft dysfunction, complement
      component deposition, circulating donor-specific antibodies (DSA), and
      histopathologic changes consistent with AMR, are infrequently present in lung
      transplantation. Nonetheless, the lung transplant community has made important
      progress recognizing cases of AMR and developing a definition. However, AMR is
      often refractory to therapy resulting in graft failure and death. In this review,
      we discuss the progress and challenges in the diagnosis and therapeutic options
      for pulmonary AMR. In addition, we briefly examine emerging paradigms of C4d
      negative AMR and chronic AMR, and conclude that significant progress is needed to
      mitigate the effects of humoral immune responses after lung transplantation.

PMID- 27896041
TI  - Flavored e-cigarette use: Characterizing youth, young adult, and adult users.
AB  - The purpose of this study is to investigate how the use of flavored e-cigarettes
      varies between youth (12-17 years old), young adults (18-29 years old), and older
      adults (30 + years old). Cross-sectional surveys of school-going youth (n = 3907)
      and young adult college students (n = 5482) in Texas, and young adults and older
      adults (n = 6051) nationwide were administered in 2014-2015. Proportions and 95%
      confidence intervals were used to describe the percentage of e-cigarette use at
      initiation and in the past 30 days that was flavored, among current e-cigarette
      users. Chi-square tests were applied to examine differences by combustible
      tobacco product use and demographic factors. Most e-cigarette users said their
      first and "usual" e-cigarettes were flavored. At initiation, the majority of
      Texas school-going youth (98%), Texas young adult college students (95%), and
      young adults (71.2%) nationwide said their first e-cigarettes were flavored to
      taste like something other than tobacco, compared to 44.1% of older adults
      nationwide. Fruit and candy flavors predominated for all groups; and, for youth,
      flavors were an especially salient reason to use e-cigarettes. Among adults, the
      use of tobacco flavor at initiation was common among dual users (e-cigarettes +
      combustible tobacco), while other flavors were more common among former cigarette
      smokers (P = 0.03). Restricting the range of e-cigarette flavors (e.g.,
      eliminating sweet flavors, like fruit and candy) may benefit youth and young
      adult prevention efforts. However, it is unclear what impact this change would
      have on adult smoking cessation.

PMID- 27896043
TI  - Health and societal effects from exposure to fragranced consumer products.
AB  - Fragranced consumer products-such as air fresheners, cleaning supplies, and
      personal care products- pervade society. This study investigated the occurrence
      and types of adverse effects associated with exposure to fragranced products in
      Australia, and opportunities for prevention. Data were collected in June 2016
      using an on-line survey with a representative national sample (n = 1098).
      Overall, 33% of Australians report health problems, such as migraine headaches
      and asthma attacks, when exposed to fragranced products. Of these health effects,
      more than half (17.1%) could be considered disabling under the Australian
      Disability Discrimination Act. Additionally, 7.7% of Australians have lost
      workdays or a job due to illness from fragranced product exposure in the
      workplace, 16.4% reported health problems when exposed to air fresheners or
      deodorizers, 15.3% from being in a room after it was cleaned with scented
      products, and 16.7% would enter but then leave a business as quickly as possible
      due to fragranced products. About twice as many respondents would prefer that
      workplaces, health care facilities and professionals, hotels, and airplanes were
      fragrance-free rather than fragranced. While 73.7% were not aware that fragranced
      products, even ones called green and organic, emitted hazardous air pollutants,
      56.3% would not continue to use a product if they knew it did. This is the first
      study in Australia to assess the extent of adverse effects associated with
      exposure to common fragranced products. It provides compelling evidence for the
      importance and value of reducing fragranced product exposure in order to reduce
      and prevent adverse health effects and costs.

PMID- 27896042
TI  - An opportunity to address modifiable breast cancer risks: Mammography screening
      and physical activity readiness to change.
AB  - Breast cancer risk is significantly reduced by improvements in lifestyle factors
      such as physical activity. Previous work suggests personal experiences such as
      false positive mammography or family history of breast cancer may influence these
      health behaviors. Surveys were distributed to women aged 40-75 who had received a
      negative mammogram from an academic hospital in Virginia in 2015. Measures
      assessed breast cancer worry and perceived risk, awareness of cancer risk
      factors, family history of breast cancer, false positive mammography experience,
      and readiness to change physical activity. Surveys were collected from 106 women.
      The regression for readiness to change physical activity was significant, F(7,
      91) = 3.7, p = 0.001, R2 = 0.22. Physical activity readiness to change was
      positively associated with income (p = 0.034) and receipt of a false positive
      mammogram (p = 0.045). African American women (p = 0.031) and women with family
      history of breast cancer (p = 0.027) reported lower readiness to change physical
      activity. Results support previous qualitative work suggesting the receipt of a
      false positive mammogram may stimulate motivation to increase physical activity.
      Mammography screening may serve as a strategic opportunity to target modifiable
      breast cancer risk factors at a time when women are highly receptive to a
      lifestyle change intervention.

PMID- 27896044
TI  - Curricular activities and change in determinants of fruit and vegetable intake
      among adolescents: Results from the Boost intervention.
AB  - Knowledge of the association between implementation of different intervention
      components and the determinants they are tailored to change may contribute to
      evaluating the effects and working mechanisms of multi-component interventions.
      This study examined 1) the effect of a Danish multi-component school-based
      intervention (2010 - 2011) on key determinants of adolescents' fruit and
      vegetable intake and 2) if dose of curricular activities was positively
      associated with change in these determinants. Using multi-level linear and
      logistic regression analyses stratified by gender and socioeconomic position, we
      analyzed survey data from the cluster-randomized Boost study targeting Danish 13
      year-olds' fruit and vegetable intake. We examined 1) differences in knowledge of
      recommendations, taste preferences and situational norms between students from 20
      intervention (n = 991) and 20 control (n = 915) schools at follow-up; and 2)
      associations between curriculum dose received and delivered (student and teacher
      data aggregated to school- and class-level) and these determinants among students
      at intervention schools only. At follow-up, more students from intervention than
      control schools knew the recommendation for vegetable intake (OR 1.56, CI:1.18,
      2.06) and number of fruits liked (taste preferences) increased by 0.22 (CI:0.04,
      0.41). At class-level, curriculum dose received was positively associated with
      proportion of students knowing the recommendation for vegetable intake (OR 1.06,
      CI:1.002, 1.13). In stratified analyses, this association was only significant
      among students from high social class (OR 1.17, CI:1.04, 1.31). The Boost
      intervention succeeded in improving students' taste preferences for fruit and
      knowledge of recommendation for vegetable intake, but only the latter determinant
      was positively associated with curriculum dose. Trial registration:
      ISRCTN11666034.

PMID- 27896046
TI  - "Applied and Translational Genomics" - What is new?

PMID- 27896045
TI  - Barriers to physical activity as moderators of intervention effects.
AB  - The impact of interventions to increase physical activity (PA) may vary as a
      function of participants' barriers to PA. The aim of this paper is to determine
      whether individual barriers (demographic, physical health, psychological health,
      neighborhood factors, perceived barriers to PA, social support for PA) moderate
      treatment effects on increases in PA. Three treatment conditions tested the
      relative efficacy of a group-based PA intervention alone or supplemented by
      either personal or automated phone calls made between group meetings. From 2010
      to 2012, 284 African American women (ages 40-65) living in the Chicago, IL, area
      were randomized to one of the three treatment conditions. Data collection
      occurred at baseline as well as 24 and 48 weeks after baseline. Moderation of
      intervention effects by barriers to PA were tested across four outcome measures
      (self-reported moderate-vigorous PA, self-reported walking, accelerometer steps,
      and aerobic fitness) using multilevel mixed-effects analyses. Significant
      condition by barrier interaction effects for the accelerometer steps outcome were
      found for material hardships, general health, depressive symptoms, neighborhood
      crime rate, and perceived barriers to PA. For aerobic fitness, intervention
      effects were moderated by material hardships and perceived pain. Increases in the
      outcome variables were greater for the conditions in which group sessions were
      supplemented with personal and/or automated calls. Among participants with
      greater barriers to PA, supplementing the intervention group meetings with
      between-session personal and/or automated phone calls may be an effective way to
      strengthen intervention effects. These results may inform the use of treatment
      supplements in the context of adaptive interventions.

PMID- 27896047
TI  - A new method for non-invasive prenatal diagnosis of Down syndrome using MeDIP
      real time qPCR.
AB  - During the last decade, the area of non-invasive prenatal diagnosis (NIPD) has
      rapidly evolved. Several methodological approaches have been presented and
      demonstrated a proof of concept for the NIPD of chromosomal aneuploidies. The two
      most promising methods are NIPD using next generation sequencing technologies and
      NIPD using Methylation DNA Immunoprecipitation (MeDIP) with real time qPCR. Both
      approaches have been validated with blind studies and have > 99% accuracy. NIPD
      using next generation sequencing is achieved by high throughput shotgun
      sequencing of DNA from plasma of maternal women followed by ratio comparisons of
      each chromosome sequence tag density over the median tag density of all autosomes
      (z-score analysis). The MeDIP real time qPCR method, which is described in this
      review in more detail, is based on the identification of differentially
      methylated regions (DMRs) and their use in discriminating normal from abnormal
      cases. More than 10,000 DMRs were identified for chromosomes 13, 18, 21, X and Y
      using high resolution oligo-arrays that can be potentially used for the NIPD of
      aneuploidies for chromosomes 13, 18, 21, X and Y. Both NIPD methods have several
      advantages and limitations and it is believed that they will soon be implemented
      in clinical practice. With the continuous advancements of genetic methodologies
      and technologies, we predict that within the next 10 years we will be able to
      provide NIPD for all common and rare genetic disorders where the molecular basis
      is known.

PMID- 27896048
TI  - Co-evolution of RNA polymerase with RbpA in the phylum Actinobacteria.
AB  - The role of RbpA in the backdrop of M. smegmatis showed that it rescues
      mycobacterial RNA polymerase from rifampicin-mediated inhibition (Dey et al.,
      2010; Dey et al., 2011). Paget and co-workers (Paget et al., 2001; Newell et al.,
      2006) have revealed that RbpA homologs occur exclusively in actinobacteria.
      Newell et al. (2006) showed that MtbRbpA, when complemented in a ?rbpA mutant of
      S. coelicolor, showed a low recovery of MIC (from 0.75 to 2 MUg/ml) as compared
      to complementation by native RbpA of S. coelicolor (MIC increases from 0.75 to 11
      MUg/ml). Our studies on MsRbpA show that it is a differential marker for M.
      smegmatis RNA polymerase as compared to E. coli RNA polymerase at IC50 levels of
      rifampicin. A recent sequence-based analysis by Lane and Darst (2010) has shown
      that RNA polymerases from Proteobacteria and Actinobacteria have had a divergent
      evolution. E. coli is a representative of Proteobacteria and M. smegmatis is an
      Actinobacterium. RbpA has an exclusive occurrence in Actinobacteria. Since
      protein-protein interactions might not be conserved across different species,
      therefore, the probable reason for the indifference of MsRbpA toward E. coli RNA
      polymerase could be the lineage-specific differences between actinobacterial and
      proteobacterial RNA polymerases. These observations led us to ask the question as
      to whether the evolution of RbpA in Actinobacteria followed the same route as
      that of RNA polymerase subunits from actinobacterial species. We show that the
      exclusivity of RbpA in Actinobacteria and the unique evolution of RNA polymerase
      in this phylum share a co-evolutionary link. We have addressed this issue by a
      blending of experimental and bioinformatics based approaches. They comprise of
      induction of bacterial cultures coupled to rifampicin-tolerance, transcription
      assays and statistical comparison of phylogenetic trees for different pairs of
      proteins in actinobacteria.

PMID- 27896049
TI  - Comprehensive characterization of genomic instability in pluripotent stem cells
      and their derived neuroprogenitor cell lines.
AB  - The genomic integrity of two human pluripotent stem cells and their derived
      neuroprogenitor cell lines was studied, applying a combination of high-resolution
      genetic methodologies. The usefulness of combining array-comparative genomic
      hybridization (aCGH) and multiplex fluorescence in situ hybridization (M-FISH)
      techniques should be delineated to exclude/detect a maximum of possible genomic
      structural aberrations. Interestingly, in parts different genomic imbalances at
      chromosomal and subchromosomal levels were detected in pluripotent stem cells and
      their derivatives. Some of the copy number variations were inherited from the
      original cell line, whereas other modifications were presumably acquired during
      the differentiation and manipulation procedures. These results underline the
      necessity to study both pluripotent stem cells and their differentiated progeny
      by as many approaches as possible in order to assess their genomic stability
      before using them in clinical therapies.

PMID- 27896050
TI  - Using in vivo electroporation to identify hepatic LDL receptor promoter elements
      and transcription factors mediating activation of transcription by T3.
AB  - The technique of in vivo electroporation was adapted to investigate the promoter
      elements and transcription factors mediating the rapid induction of hepatic LDL
      receptor expression in response to thyroid hormone. Direct comparisons between
      wild type and mutant promoter constructs were made within the same animal. It was
      demonstrated that both TREs at bp - 612 and - 156 were required for the l
      triiodothyronine (T3) response. ChIP analysis showed that binding of TRbeta1 to
      the - 612 and - 156 TREs was markedly stimulated by T3in vivo. Introduction of
      siRNAs against TRbeta1/RXRalpha with LDL receptor promoter-luciferase construct
      by in vivo electroporation demonstrated that these transcription factors play the
      major physiological role in the activation of hepatic LDL receptor transcription.
      The findings agree with those made by transfecting H4IIE cells in vitro thus
      validating this technique for in vivo studies of mechanisms of transcriptional
      regulation. The findings reported herein also indicated, for the first time, that
      PPARalpha and USF-2 were required for maximum transcriptional activation of the
      LDL receptor in response to T3 treatment.

PMID- 27896051
TI  - Screening of mutations affecting protein stability and dynamics of FGFR1-A
      simulation analysis.
AB  - Single amino acid substitutions in Fibroblast Growth Factor Receptor 1 (FGFR1)
      destabilize protein and have been implicated in several genetic disorders like
      various forms of cancer, Kallamann syndrome, Pfeiffer syndrome, Jackson Weiss
      syndrome, etc. In order to gain functional insight into mutation caused by amino
      acid substitution to protein function and expression, special emphasis was laid
      on molecular dynamics simulation techniques in combination with in silico tools
      such as SIFT, PolyPhen 2.0, I-Mutant 3.0 and SNAP. It has been estimated that 68%
      nsSNPs were predicted to be deleterious by I-Mutant, slightly higher than SIFT
      (37%), PolyPhen 2.0 (61%) and SNAP (58%). From the observed results, P722S
      mutation was found to be most deleterious by comparing results of all in silico
      tools. By molecular dynamics approach, we have shown that P722S mutation leads to
      increase in flexibility, and deviated more from the native structure which was
      supported by the decrease in the number of hydrogen bonds. In addition,
      biophysical analysis revealed a clear insight of stability loss due to P722S
      mutation in FGFR1 protein. Majority of mutations predicted by these in silico
      tools were in good concordance with the experimental results.

PMID- 27896053
TI  - Introduction to evolutionary genomic approaches to human disease.

PMID- 27896052
TI  - Mutation analysis of the candidate genes SCN1B-4B, FHL1, and LMNA in patients
      with arrhythmogenic right ventricular cardiomyopathy.
AB  - INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a
      genetically determined heart disease characterized by fibrofatty infiltrations in
      the myocardium, right and/or left ventricular involvement, and ventricular
      tachyarrhythmias. Although ten genes have been associated with ARVC, only about
      40% of the patients have an identifiable disease-causing mutation. In the present
      study we aimed at investigating the involvement of the genes SCN1B-SCN4B, FHL1,
      and LMNA in the pathogenesis of ARVC. METHODS: Sixty-five unrelated patients (55
      fulfilling ARVC criteria and 10 borderline cases) were screened for variants in
      SCN1B-4B, FHL1, and LMNA by direct sequencing and LightScanner melting curve
      analysis. RESULTS: A total of 28 sequence variants were identified: seven in
      SCN1B, three in SCN2B, two in SCN3B, two in SCN4B, four in FHL1, and ten in LMNA.
      Three of the variants were novel. One of the variants was non-synonymous. No
      disease-causing mutations were identified. CONCLUSIONS: In our limited sized
      cohort the six studied candidate genes were not associated with ARVC.

PMID- 27896054
TI  - Disease consequences of human adaptation.
AB  - Adaptive evolution has provided us with a unique set of characteristics that
      define us as humans, including morphological, physiological and cellular changes.
      Yet, natural selection provides no assurances that adaptation is without human
      health consequences; advantageous mutations will increase in frequency so long as
      there is a net gain in fitness. As such, the current incidence of human disease
      can depend on previous adaptations. Here, I review genome-wide and gene-specific
      studies in which adaptive evolution has played a role in shaping human genetic
      disease. In addition to the disease consequences of adaptive phenotypes, such as
      bipedal locomotion and resistance to certain pathogens, I review evidence that
      adaptive mutations have influenced the frequency of linked disease alleles
      through genetic hitchhiking. Taken together, the links between human adaptation
      and disease highlight the importance of their combined influence on functional
      variation within the human genome and offer opportunities to discover and
      characterize such variation.

PMID- 27896055
TI  - Phylooncogenomics: Examining the cancer genome in the context of vertebrate
      evolution.
AB  - Currently, human cancer genomics is making great progress, and many mutations of
      new cancer driver genes have been detected at an unprecedented rate in a variety
      of human cancers. Many details of the genetic alterations in cancer cell genomes
      have been revealed by the massively parallel sequencing. Long-lasting aneuploidy
      caused large-scale somatic copy number alterations remains a difficulty as there
      are too many genes located on such big chromosomal fragments, and this cannot
      simply be solved by increasing sequencing depth and tumor sample numbers.
      Comparative oncogenomics may provide us with a solution to this problem. Here, we
      review some of the common animal cancer models and propose to analyze cancer cell
      genomics in vertebrate phylogenetic backgrounds. Thus phylooncogenomics may
      provide us with a unique perspective on he nature of cancer biology unattainable
      by single species studies.

PMID- 27896056
TI  - Maternal regulation of offspring development in mammals is an ancient adaptation
      tied to lactation.
AB  - The developmental origins of health and disease (DOHaD) is a paradigm for
      understanding metabolic diseases of modern humans. Vulnerability to disease is
      linked to perturbations in development during critical time periods in fetal and
      neonatal life. These perturbations are caused by environmental signals, often
      generated or transduced by the mother. The regulation of mammalian development
      depends to a large extent on maternal biochemical signals to her offspring. We
      argue that this adaptation is ancient, and originated with the evolution of
      lactation. Lactation evolved earlier than live birth and before the extensive
      placental development of modern eutherian mammals. Milk contains a host of
      signaling molecules including nutrients, immunoglobulins, growth factors and
      metabolic hormones. As evidenced by marsupials, lactation originally served to
      supply the biochemical factors for growth and development for what is essentially
      a fetus to a weanling transitioning to independent existence. In placental
      mammals maternal signaling in earliest life is accomplished through the maternal
      placental-fetal connection, with more of development shifted to in utero life.
      However, significant development occurs postpartum, supported by milk. Mothers of
      all taxa provide biochemical signals to their offspring, but for non-mammalian
      mothers the time window is short. Developing mammals receive maternal biochemical
      signals over an extended period. These signals serve to guide normal development,
      but also can vary in response to environmental conditions. The ancient adaptation
      of lactation resulted in a lineage (mammals) in which maternal regulation of
      offspring development evolved to a heightened degree, with the ability to modify
      development at multiple time points. Modern metabolic diseases may arise due to a
      mismatch between maternal regulation and eventual circumstances of the offspring,
      and due to a large proportion of mothers that exceed past evolutionary norms in
      body fat and pregnancy weight gain such that maternal signals may no longer be
      within the adaptive range.

PMID- 27896057
TI  - Evolutionary perspectives into placental biology and disease.
AB  - In all mammals including humans, development takes place within the protective
      environment of the maternal womb. Throughout gestation, nutrients and waste
      products are continuously exchanged between mother and fetus through the
      placenta. Despite the clear importance of the placenta to successful pregnancy
      and the health of both mother and offspring, relatively little is understood
      about the biology of the placenta and its role in pregnancy-related diseases.
      Given that pre- and peri-natal diseases involving the placenta affect millions of
      women and their newborns worldwide, there is an urgent need to understand
      placenta biology and development. Here, we suggest that the placenta is an organ
      under unique selective pressures that have driven its rapid diversification
      throughout mammalian evolution. The high divergence of the placenta complicates
      the use of non-human animal models and necessitates an evolutionary perspective
      when studying its biology and role in disease. We suggest that diversifying
      evolution of the placenta is primarily driven by intraspecies evolutionary
      conflict between mother and fetus, and that many pregnancy diseases are a
      consequence of this evolutionary force. Understanding how maternal-fetal conflict
      shapes both basic placental and reproductive biology - in all species - will
      provide key insights into diseases of pregnancy.

PMID- 27896058
TI  - From PPROM to caul: The evolution of membrane rupture in mammals.
AB  - Rupture of the extraembryonic membranes that form the gestational sac in humans
      is a typical feature of human parturition. However, preterm premature rupture of
      membranes (PPROM) occurs in approximately 1% of pregnancies, and is a leading
      cause of preterm birth. Conversely, retention of an intact gestational sac during
      parturition in the form of a caul is a rare occurrence. Understanding the
      molecular and evolutionary underpinnings of these disparate phenotypes can
      provide insight into both normal pregnancy and PPROM. Using phylogenetic
      techniques we reconstructed the evolution of the gestational sac phenotype at
      parturition in 55 mammal species representing all major viviparous mammal groups.
      We infer the ancestral state in therians, eutherians, and primates, as in humans,
      is a ruptured gestational sac at parturition. We present evidence that intact
      membranes at parturition have evolved convergently in diverse mammals including
      horses, elephants, and bats. In order to gain insight into the molecular
      underpinnings of the evolution of enhanced membrane integrity we also used
      comparative genomics techniques to reconstruct the evolution of a subset of genes
      implicated in PPROM, and find that four genes (ADAMTS2, COL1A1, COL5A1, LEPRE1)
      show significant evidence of increased nonsynonymous rates of substitution on
      lineages with intact membranes as compared to those with ruptured membranes.
      Among these genes, we also discovered that 17 human SNPs are associated with or
      near amino acid replacement sites in those mammals with intact membranes. These
      SNPs are candidate functional variants within humans, which may play roles in
      both PPROM and/or the retention of the gestational sac at birth.

PMID- 27896060
TI  - Diffuse bronchiectasis as the primary manifestation of endobronchial sarcoidosis.
AB  - Sarcoidosis is an idiopathic disease that most commonly involves the lungs and is
      characterized by granulomatous inflammation. Bronchiectasis is one pulmonary
      manifestation of sarcoidosis, although it is almost always observed as traction
      bronchiectasis in the setting of fibrotic lung disease. A 50-year-old woman was
      evaluated for chronic cough and bronchiectasis with a small amount of peripheral
      upper lobe honeycombing and no significant pulmonary fibrosis or lymphadenopathy.
      After an extensive laboratory and imaging evaluation did not identify a cause of
      her bronchiectasis, bronchoscopy was performed to assess for primary ciliary
      dyskinesia and revealed a diffuse cobblestone appearance of the airway mucosa.
      Endobronchial biopsies and lymphocyte subset analysis of bronchoalveolar lavage
      fluid were consistent with a diagnosis of sarcoidosis. We believe endobronchial
      sarcoidosis should be included in the differential diagnosis of patients
      presenting with bronchiectasis.

PMID- 27896061
TI  - Successful retreatment with osimertinib after osimertinib-induced acute pulmonary
      embolism in a patient with lung adenocarcinoma: A case report.
AB  - Pulmonary embolism (PE) can be life-threatening, and it is challenging to
      diagnose because of its nonspecific signs and symptoms. PE is also an important
      potential risk of osimertinib treatment, however, clinical courses regarding
      retreatment after osimertinib-induced acute pulmonary embolism remain unclear. We
      described a 77-year-old woman with postoperative recurrent lung adenocarcinoma
      who developed osimertinib-induced acute PE. She received apixaban and was later
      successfully retreated with osimertinib. This case suggests that retreatment with
      osimertinib after osimertinib-induced acute PE may be a treatment option when
      alternative therapeutic options are limited.

PMID- 27896062
TI  - Acute fibrinous and organizing pneumonia in a patient with Sjogren's syndrome.
AB  - Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern
      characterized by intra-alveolar fibrin deposition and associated organizing
      pneumonia. AFOP has been associated with many rheumatologic disorders in the
      literature but has not been described in association with Sjogren's syndrome.
      This paper shows a rare association of AFOP with Sjogren's syndrome. Patient's
      symptoms promptly improved after treatment with steroid.

PMID- 27896059
TI  - Signatures of natural selection on genetic variants affecting complex human
      traits.
AB  - It has recently been hypothesized that polygenic adaptation, resulting in modest
      allele frequency changes at many loci, could be a major mechanism behind the
      adaptation of complex phenotypes in human populations. Here we leverage the large
      number of variants that have been identified through genome-wide association
      (GWA) studies to comprehensively study signatures of natural selection on genetic
      variants associated with complex traits. Using population differentiation based
      methods, such as FST and phylogenetic branch length analyses, we systematically
      examined nearly 1300 SNPs associated with 38 complex phenotypes. Instead of
      detecting selection signatures at individual variants, we aimed to identify
      combined evidence of natural selection by aggregating signals across many trait
      associated SNPs. Our results have revealed some general features of polygenic
      selection on complex traits associated variants. First, natural selection acting
      on standing variants associated with complex traits is a common phenomenon.
      Second, characteristics of selection for different polygenic traits vary both
      temporarily and geographically. Third, some studied traits (e.g. height and urate
      level) could have been the primary targets of selection, as indicated by the
      significant correlation between the effect sizes and the estimated strength of
      selection in the trait associated variants; however, for most traits, the allele
      frequency changes in trait associated variants might have been driven by the
      selection on other correlated phenotypes. Fourth, the changes in allele
      frequencies as a result of selection can be highly stochastic, such that,
      polygenic adaptation may accelerate differentiation in allele frequencies among
      populations, but generally does not produce predictable directional changes.
      Fifth, multiple mechanisms (pleiotropy, hitchhiking, etc) may act together to
      govern the changes in allele frequencies of genetic variants associated with
      complex traits.

PMID- 27896063
TI  - Necrotizing tracheobronchitis associated with rheumatoid arthritis.
AB  - We report a case of necrotizing tracheobronchitis with rheumatoid arthritis. A 64
      year-old-man presented with dry cough and was initially diagnosed with community
      acquired pneumonia. The patient was admitted; he received initial antibiotic
      treatment. The treatment was effective and the symptoms worsened. Bronchoscopy
      was performed for more thorough examination. It showed that white and soft
      tissues were on the trachea-bronchus. Transbronchial biopsy of the tracheal
      lesions revealed necrotic tissue with squamous metaplasia and inflammatory cells.
      Whereas, symmetrical arthralgia of multiple joints of the limbs was noted and
      rheumatoid factor and anti-cyclic citrullinated peptide antibody of levels were
      high. According to these results, the patient was diagnosed with rheumatoid
      arthritis. In this case, necrotizing tracheobronchitis occurred as a result of
      systemic inflammation associated with rheumatoid arthritis. An acute exacerbation
      of the patient's respiratory condition was treated with steroid therapy. Tracheal
      findings and respiratory symptoms were improved by steroid therapy.

PMID- 27896064
TI  - Executive attention networks show altered relationship with default mode network
      in PD.
AB  - Attention dysfunction is a common but often undiagnosed cognitive impairment in
      Parkinson's disease that significantly reduces quality of life. We sought to
      increase understanding of the mechanisms underlying attention dysfunction using
      functional neuroimaging. Functional MRI was acquired at two repeated sessions in
      the resting state and during the Attention Network Test, for 25 non-demented
      subjects with Parkinson's disease and 21 healthy controls. Behavioral and MRI
      contrasts were calculated for alerting, orienting, and executive control
      components of attention. Brain regions showing group differences in attention
      processing were used as seeds in a functional connectivity analysis of a separate
      resting state run. Parkinson's disease subjects showed more activation during
      increased executive challenge in four regions of the dorsal attention and
      frontoparietal networks, namely right frontal eye field, left and right
      intraparietal sulcus, and precuneus. In three regions we saw reduced resting
      state connectivity to the default mode network. Further, whereas higher task
      activation in the right intraparietal sulcus correlated with reduced resting
      state connectivity between right intraparietal sulcus and the precuneus in
      healthy controls, this relationship was absent in Parkinson's disease subjects.
      Our results suggest that a weakened interaction between the default mode and task
      positive networks might alter the way in which the executive response is
      processed in PD.

PMID- 27896066
TI  - ACTH therapy for West syndrome with severe hemophilia A.
AB  - Hemophilia A is an X-linked recessive disorder caused by factor VIII deficiency,
      which is an important factor in the coagulation system. Here, we describe a 1
      year-old boy with hemophilia A who developed West syndrome (WS). Recombinant
      factor VIII was administered during adrenocorticotropic hormone (ACTH) therapy to
      prevent intracranial hemorrhage. Infusion of factor VIII at fixed intervals is
      useful for the safe administration of ACTH therapy for patients with WS with
      severe hemophilia A. A coagulation screening test should be performed before ACTH
      therapy.

PMID- 27896065
TI  - Analysis of ageing-associated grey matter volume in patients with multiple
      sclerosis shows excess atrophy in subcortical regions.
AB  - Age of onset in multiple sclerosis (MS) exerts an influence on the course of
      disease. This study examined whether global and regional brain volumes differed
      between "younger" and "older" onset MS subjects who were matched for short
      disease duration, mean 1.9 years and burden as measured by the MS Severity Score
      and relapses. 21 younger-onset MS subjects (age 30.4 +/- 3.2 years) were compared
      with 17 older-onset (age 48.7 +/- 3.3 years) as well as age-matched controls (n =
      31, 31.9 +/- 3.5 years and n = 21, 47.3 +/- 4.0 years). All subjects underwent 3D
      volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM)
      lesions were outlined manually. Lesions were filled prior to tissue and
      structural segmentation to reduce classification errors. Volume loss versus
      control was predominantly in the subcortical GM, at > 13% loss. Younger and older
      onset MS subjects had similar, strong excess loss in the putamen, thalamus, and
      nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The
      hippocampus and caudate showed significant excess loss in the younger group (p <
      0.001) and a strong trend in the older-onset group. These results provide a
      potential imaging correlate of published neuropsychological studies that reported
      the association of younger age at disease onset with impaired cognitive
      performance, including decreased working memory.

PMID- 27896067
TI  - Relationship between high-frequency oscillations and spikes in a case of temporal
      lobe epilepsy.
AB  - OBJECTIVE: The aim of this case report was to study the relationship between high
      frequency oscillations (HFOs), spikes, and seizures in a patient with temporal
      lobe epilepsy. INTRODUCTION: During intracranial electroencephalography (EEG),
      HFOs are thought to be a marker for the seizure onset zone (SOZ). High-frequency
      oscillations are classified into ripples with frequencies of 70-200 Hz and fast
      ripples with frequencies of 200-500 Hz. Although HFOs are thought to be a marker
      for the SOZ, their relationship to spikes has not been studied in detail,
      especially within the SOZ. METHODS: We studied the time course of ripples and
      spikes in a patient undergoing intracranial EEG. Medications were discontinued on
      day one. She suffered three seizures on day three. Her SOZ was in the left
      hippocampus, which displayed abundant ripples and spikes. Ripples, spikes with
      simultaneous ripples, and spikes without ripples were counted for this study.
      RESULTS: We found that ripples and spikes in the SOZ had a marked diurnal
      variation. Ripples, spikes with ripples, and spikes without ripples increased and
      decreased in concert until just before seizure onset, when ripples and spikes
      with ripples increased markedly. Spikes without ripples did not increase.
      CONCLUSIONS: These results support ripples as a marker for SOZ and show that they
      co-occur with spikes. Seizure onset was heralded by an increase in ripples and
      spikes with ripples, without an increase in spikes without ripples. We
      hypothesize that spikes associated with ripples may have a somewhat different
      pathophysiological mechanism than spikes not associated with ripples, differences
      that may be relevant for the timing of seizure onset.

PMID- 27896068
TI  - Metagenomic investigation of the microbial diversity in a chrysotile asbestos
      mine pit pond, Lowell, Vermont, USA.
AB  - Here we report on a metagenomics investigation of the microbial diversity in a
      serpentine-hosted aquatic habitat created by chrysotile asbestos mining activity
      at the Vermont Asbestos Group (VAG) Mine in northern Vermont, USA. The now
      abandoned VAG Mine on Belvidere Mountain in the towns of Eden and Lowell includes
      three open-pit quarries, a flooded pit, mill buildings, roads, and > 26 million
      metric tons of eroding mine waste that contribute alkaline mine drainage to the
      surrounding watershed. Metagenomes and water chemistry originated from aquatic
      samples taken at three depths (0.5 m, 3.5 m, and 25 m) along the water column at
      three distinct, offshore sites within the mine's flooded pit (near 44 degrees
      46'00.7673", - 72 degrees 31'36.2699"; UTM NAD 83 Zone 18 T 0695720 E, 4960030
      N). Whole metagenome shotgun Illumina paired-end sequences were quality trimmed
      and analyzed based on a translated nucleotide search of NCBI-NR protein database
      and lowest common ancestor taxonomic assignments. Our results show strata within
      the pit pond water column can be distinguished by taxonomic composition and
      distribution, pH, temperature, conductivity, light intensity, and concentrations
      of dissolved oxygen. At the phylum level, metagenomes from 0.5 m and 3.5 m
      contained a similar distribution of taxa and were dominated by Actinobacteria
      (46% and 53% of reads, respectively), Proteobacteria (45% and 38%, respectively),
      and Bacteroidetes (7% in both). The metagenomes from 25 m showed a greater
      diversity of phyla and a different distribution of reads than the two upper
      strata: Proteobacteria (60%), Actinobacteria (18%), Planctomycetes, (10%),
      Bacteroidetes (5%) and Cyanobacteria (2.5%), Armatimonadetes (< 1%),
      Verrucomicrobia (< 1%), Firmicutes (< 1%), and Nitrospirae (< 1%). Raw metagenome
      sequence data from each sample reside in NCBI's Short Read Archive (SRA ID:
      SRP056095) and are accessible through NCBI BioProject PRJNA277916.

PMID- 27896070
TI  - Metagenome sequencing of the microbial community of two Brazilian anthropogenic
      Amazon dark earth sites, Brazil.
AB  - The Anthropogenic Amazon Dark Earth soil is considered one of the world's most
      fertile soils. These soils differs from conventional Amazon soils because its
      higher organic content concentration. Here we describe the metagenome sequencing
      of microbial communities of two sites of Anthropogenic Amazon Dark Earth soils
      from Amazon Rainforest, Brazil. The raw sequence data are stored under Short Read
      Accession number: PRJNA344917.

PMID- 27896069
TI  - Evaluation of de novo assembly technique in the South African abalone Haliotis
      midae transcriptome: A comparison from Illumina and 454 systems.
AB  - Next generation sequencing platforms have recently been used to rapidly
      characterize transcriptome sequences from a number of non-model organisms. The
      present study compares two of the most frequently used platforms, the Roche 454
      pyrosequencing and the Illumina sequencing-by-synthesis (SBS), on the same RNA
      sample obtained from an intertidal gastropod mollusc species, Haliotis midae. All
      the sequencing reads were deposited in the Short Read Archive (SRA) database are
      retrievable under the accession number [SRR071314 (Illumina Genome Analyzer II)]
      and [SRR1737738, SRR1737737, SRR1737735, SRR1737734 (454 GS FLX)] in the SRA
      database of NCBI. Three transcriptomes, composed of either pure 454 or Illumina
      reads or a mixture of read types (Hybrid), were assembled using CLC Genomics
      Workbench software. Illumina assemblies performed the best de novo transcriptome
      characterization in terms of contig length, whereas the 454 assemblies tended to
      improve the complete assembly of gene transcripts. Both the Hybrid and Illumina
      assemblies produced longer contigs covering more of the transcriptome than 454
      assemblies. However, the addition of 454 significantly increased the number of
      genes annotated.

PMID- 27896071
TI  - Draft genome sequence of Thermoactinomyces sp. Gus2-1 isolated from the hot
      spring Gusikha in Bargusin Valley (Baikal Rift Zone, Russia).
AB  - The Thermoactinomyces sp. strain Gus2-1 was isolated from hot-spring sediments
      sample from the hot-spring Gusikha in Bargusin Valley (Baikal Rift Zone, Russia).
      The sequenced and annotated genome is 2,623,309 bp and encodes 2513 genes. The
      draft genome sequence of the Thermoactinomyces sp. strain Gus2-1 has been
      deposited at DDBJ/EMBL/GenBank under the accession JPZM01000000 and the sequences
      could be found at the site https://www.ncbi.nlm.nih.gov/nuccore/JPZM01000000.

PMID- 27896072
TI  - Influence of Npc1 genotype on the toxicity of hydroxypropyl-beta-cyclodextrin, a
      potentially therapeutic agent, in Niemann-Pick Type C disease models.
AB  - Hydroxypropyl-beta-cyclodextrin (HPBCD) is an attractive drug candidate against
      Niemann-Pick Type C (NPC) disease. However, the safety of HPBCD treatment for NPC
      patients remains to be elucidated. In this study, we examined the acute toxicity
      of HPBCD in Npc1-deficient mice. When treated with HPBCD (20,000 mg/kg,
      subcutaneously), over half of the wild-type (Npc1+/+) or Npc1+/- mice died by 72
      h after the injection. In contrast, all of the Npc1-/- mice survived. Marked
      pathophysiological changes, such as an elevation in serum transaminase and
      creatinine levels, hepatocellular necrosis, renal tubular damage, interstitial
      thickening, and hemorrhages in lungs, were induced by the HPBCD treatment in
      Npc1+/+ or Npc1+/- mice. However, these pathophysiological changes were
      significantly alleviated in Npc1-/- mice. In addition, in vitro analysis showed
      that the Npc1 gene deficiency and treatment with U18666A, an Npc1 inhibitor,
      remarkably attenuated the cytotoxicity of HPBCD in Chinese hamster ovary cells.
      These results suggest that the NPC1 genotype exacerbates the cytotoxicity of
      HPBCD and Npc1-/- mice have substantial resistance to the lethality and the organ
      injury induced by HPBCD injection compared with Npc1+/+ or Npc1+/- mice. We
      suggest that the Npc1 genotype should be considered in the safety evaluation of
      HPBCD using experimental animals and cells.

PMID- 27896074
TI  - Effect of isolated AMP deaminase deficiency on skeletal muscle function.
AB  - Mutation of the AMP deaminase 1 (AMPD1) gene, the predominate AMPD gene expressed
      in skeletal muscle, is one of the most common inherited defects in the Caucasian
      population; 2-3% of individuals in this ethnic group are homozygous for defects
      in the AMPD1 gene. Several studies of human subjects have reported variable
      results with some studies suggesting this gene defect may cause symptoms of a
      metabolic myopathy and/or easy fatigability while others indicate individuals
      with this inherited defect are completely asymptomatic. Because of confounding
      problems in assessing muscle symptoms and performance in human subjects with
      different genetic backgrounds and different environmental experiences such as
      prior exercise conditioning and diet, a strain of inbred mice with selective
      disruption of the AMPD1 was developed to study the consequences of muscle AMPD
      deficiency in isolation. Studies reported here demonstrate that these animals are
      a good metabolic phenocopy of human AMPD1 deficiency but they exhibit no
      abnormalities in muscle performance in three different exercise protocols.

PMID- 27896075
TI  - The value of neuroimaging in the assessment and follow-up of early-onset
      methylmalonic aciduria and homocystinuria.

PMID- 27896073
TI  - Medium-chain triglyceride supplementation under a low-carbohydrate formula is a
      promising therapy for adult-onset type II citrullinemia.
AB  - BACKGROUND: Citrin, encoded by SLC25A13, is a component of the malate-aspartate
      shuttle, which is the main NADH-transporting system in the liver. Citrin
      deficiency causes neonatal intrahepatic cholestasis (NICCD), which usually
      resolves within the first year of life. However, small numbers of adults with
      citrin deficiency develop hyperammonemic encephalopathy, adult-onset type II
      citrullinemia (CTLN2), which leads to death due to cerebral edema. Liver
      transplantation is the only definitive therapy for patients with CTLN2. We
      previously reported that a lactose (galactose)-restricted and medium-chain
      triglyceride (MCT)-supplemented formula is notably effective for patients with
      NICCD. Citrin deficiency may impair the glycolysis in hepatocytes because of an
      increase in the cytosolic NADH/NAD+ ratio, leading to an energy shortage. MCT
      administration can provide energy to hepatocytes and was expected to have a good
      effect on CTLN2. METHODS: An MCT supplementation therapy under a low-carbohydrate
      formula was administered to five patients with CTLN2. Four of the patients had
      episodes of hyperammonemic encephalopathy, and one patient had postprandial
      hyperammonemia with no symptoms. RESULTS: One of the patients displaying
      hyperammonemic encephalopathy completely recovered with all normal laboratory
      findings. Others notably improved in terms of clinical and or laboratory findings
      with no hyperammonemic symptoms; however, the patients displayed persistent mild
      citrullinemia and occasionally had postprandial mild hyperammonemia most likely
      due to an irreversible change in the liver. CONCLUSIONS: An MCT supplement can
      provide energy to hepatocytes and promote hepatic lipogenesis, leading to a
      reduction in the cytosolic NADH/NAD+ ratio. MCT supplementation under a low
      carbohydrate formula could be a promising therapy for CTLN2 and should also be
      used to prevent CTLN2 to avoid irreversible liver damage.

PMID- 27896076
TI  - Thiamine pyrophosphokinase deficiency causes a Leigh Disease like phenotype in a
      sibling pair: identification through whole exome sequencing and management
      strategies.
AB  - We present a sibling pair with Leigh-like disease, progressive hypotonia,
      regression, and chronic encephalopathy. Whole exome sequencing in the younger
      sibling demonstrated a homozygous thiamine pyrophosphokinase (TPK) mutation.
      Initiation of high dose thiamine, niacin, biotin, alpha-lipoic acid and ketogenic
      diet in this child demonstrated improvement in neurologic function and re
      attainment of previously lost milestones. The diagnosis of TPK deficiency was
      difficult due to inconsistent biochemical and diagnostic parameters, rapidity of
      clinical demise and would not have been made in a timely manner without the use
      of whole exome sequencing. Molecular diagnosis allowed for attempt at dietary
      modification with cofactor supplementation which resulted in an improved clinical
      course.

PMID- 27896078
TI  - Risk factors for osteoporosis, falls and fractures in hereditary myopathies and
      sporadic inclusion body myositis - A cross sectional survey.
AB  - BACKGROUND: The risk of osteoporosis is known in myopathies requiring long-term
      steroid treatment and Pompe disease, but not in other hereditary myopathies or
      sporadic inclusion body myositis (sIBM). METHODS: Risk factors of osteoporosis,
      laboratory parameters of bone metabolism, frequency of falls and fractures,
      walking ability, and pain were surveyed using questionnaires in 89 patients with
      sIBM and genetically confirmed myopathies facioscapulohumeral muscular dystrophy
      (FSHD), myotonic dystrophy types 1 and 2 (DM1, DM2), limb girdle muscular
      dystrophies (LGMD2A, LGMD2B, LGMD2I), MATR3 myopathy, and oculopharyngeal
      muscular dystrophy (OPMD). Additionally laboratory parameters of bone metabolism
      were determined. RESULTS: The mean age at examination per disease group ranged
      from 32 years in LGMD2A to 70 years in sIBM. Myopathies with a higher degree of
      walking impairment had a higher risk of falls (sIBM, LGMD2A, LGMD2B). At the time
      of examination 3.4% had a history of osteoporosis. The 25-OH D3 level was
      decreased in 20% of patients (and in 55% of patients with LGMDs), 57% of them
      were ambulatory. The 25-OH D3 level was significantly lower in patients with
      myopathies than in other neurological disorders (p < 0.001). 2.7 falls per year
      per person occurred. Fractures were reported in 6.8% of patients within the last
      year. They involved frequently the tibia bone. The pain score didn't correlate
      with either the walking disability (WGMS) score or the 25-OH D3 level.
      CONCLUSION: The risk for osteoporosis and reduced 25-OH D3 level seems to be
      increased in wheelchair-bound patients with myopathy but also in patients with
      DM1 and autosomal-recessive myopathies.

PMID- 27896077
TI  - Sequencing analysis of insulin receptor defects and detection of two novel
      mutations in INSR gene.
AB  - : Mutations in the insulin receptor gene cause the inherited insulin resistant
      syndromes Leprechaunism and Rabson-Mendenhall syndrome. These recessive
      conditions are characterized by intrauterine and post-natal growth restrictions,
      dysmorphic features, altered glucose homeostasis, and early demise. The insulin
      receptor gene (INSR) maps to the short arm of chromosome 19 and is composed of 22
      exons. Here we optimize the conditions for sequencing this gene and report novel
      mutations in patients with severe insulin resistance. METHODS: PCR amplification
      of the 22 coding exons of the INSR gene was performed using M13-tailed primers.
      Bidirectional DNA sequencing was performed with BigDye Terminator chemistry and
      M13 primers and the product was analyzed on the ABI 3100 genetic analyzer. Data
      analysis was performed using Mutation Surveyor software comparing the sequence to
      a reference INSR sequence (Genbank NC_000019). RESULTS: We sequenced four
      patients with Leprechaunism or Rabson-Mendenhall syndromes as well as seven
      samples from normal individuals and confirmed previously identified mutations in
      the affected patients. Three of the four mutations identified in this group
      caused premature insertion of a stop codon. In addition, the INSR gene was
      sequenced in 14 clinical samples from patients with suspected insulin resistance
      and one novel mutation was found in an infant with a suspected diagnosis of
      Leprechaunism. DISCUSSION: Leprechaunism and Rabson-Mendenhall syndrome are very
      rare and difficult to diagnose. Diagnosis is currently based mostly on clinical
      criteria. Clinical availability of DNA sequencing can provide an objective way of
      confirming or excluding the diagnosis.

PMID- 27896079
TI  - A de novo or germline mutation in a family with Mucolipidosis III gamma:
      Implications for molecular diagnosis and genetic counseling.
AB  - Mucolipidosis III (ML III) gamma is a very rare autosomal-recessive disorder
      characterized by the abnormal trafficking and subcellular localization of
      lysosomal enzymes due to mutations in the GNPTG gene. The present study consists
      of a report of a Brazilian compound heterozygote patient with ML III gamma
      resulting from one mutant paternal allele and one allele that had most likely
      undergone a de novo or maternal germline mutation. This is the first report of a
      de novo mutation in ML III gamma. This finding has significant implications for
      genetic counseling.

PMID- 27896080
TI  - Lysine-restricted diet and mild cerebral serotonin deficiency in a patient with
      pyridoxine-dependent epilepsy caused by ALDH7A1 genetic defect.
AB  - Pyridoxine dependent epilepsy (PDE) is caused by mutations in the ALDH7A1 gene
      (PDE-ALDH7A1) encoding alpha-aminoadipic-semialdehyde-dehydrogenase enzyme in the
      lysine catabolic pathway resulting in an accumulation of alpha-aminoadipic-acid
      semialdehyde (alpha-AASA). We present the one-year treatment outcome of a patient
      on a lysine-restricted diet. Serial cerebral-spinal-fluid (CSF) alpha-AASA and
      CSF pipecolic-acid levels showed decreased levels but did not normalize. He had a
      normal neurodevelopmental outcome on a lysine-restricted diet. Despite normal CSF
      and plasma tryptophan levels and normal tryptophan intake, he developed mild CSF
      serotonin deficiency at one year of therapy. Stricter lysine restriction would be
      necessary to normalize CSF alpha-AASA levels, but might increase the risks
      associated with the diet. Patients are at risk of cerebral serotonin deficiency
      and should be monitored by CSF neurotransmitter measurements.

PMID- 27896083
TI  - Pain in adult patients with Pompe disease.

PMID- 27896081
TI  - Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase
      deficiency.
AB  - The pathophysiology of succinic semialdehyde dehydrogenase (SSADH) deficiency is
      not completely understood. Oxidative stress, mitochondrial pathology, and low
      reduced glutathione levels have been demonstrated in mice, but no studies have
      been reported in humans. We report on a patient with SSADH deficiency in whom we
      found low levels of blood reduced glutathione (GSH), and elevations of
      dicarboxylic acids in urine, suggestive of possible redox imbalance and/or
      mitochondrial dysfunction. Thus, targeting the oxidative stress axis may be a
      potential therapeutic approach if our findings are confirmed in other patients.

PMID- 27896082
TI  - A rapid screening with direct sequencing from blood samples for the diagnosis of
      Leigh syndrome.
AB  - Large numbers of genes are responsible for Leigh syndrome (LS), making genetic
      confirmation of LS difficult. We screened our patients with LS using a limited
      set of 21 primers encompassing the frequently reported gene for the respiratory
      chain complexes I (ND1-ND6, and ND4L), IV(SURF1), and V(ATP6) and the pyruvate
      dehydrogenase E1alpha-subunit. Of 18 LS patients, we identified mutations in 11
      patients, including 7 in mDNA (two with ATP6), 4 in nuclear (three with SURF1).
      Overall, we identified mutations in 61% of LS patients (11/18 individuals) in
      this cohort. Sanger sequencing with our limited set of primers allowed us a rapid
      genetic confirmation of more than half of the LS patients and it appears to be
      efficient as a primary genetic screening in this cohort.

PMID- 27896084
TI  - Accuracy of formula preparation equipment for liquid measurement.
AB  - BACKGROUND: Modular specialist feeds may consist of a number of individual liquid
      ingredients. Accurate feed preparation is dependent on competent liquid
      measurement. We investigate the accuracy of two measuring jugs (one retail mix
      and-measure; and one produced to laboratory standards); and the influence of
      volume and technique on accuracy. MATERIALS AND METHODS: 20 health professionals
      aged 18-60 y (mean: 46 y) measured 3 different volumes of water with each of two
      measuring jugs. For each volume with each jug, 2 measurements in randomised order
      were made: 1) eye-level with the jug, and 2) standing upright (total of 12
      measurements). Measured quantities were weighed and the difference between
      measured and target volumes calculated. RESULTS: The laboratory jug was more
      accurate (mean difference 9.3 ml, range - 30.5 to 57.5 ml, std error mean 1.59)
      than the retail jug (mean difference - 17.7 ml, range - 92.0 to 48.5 ml, std
      error mean 1.59). Accuracy improved with increased volume (450 ml: mean
      difference - 9.4 ml, range - 75.5 to 49.5 ml, std error mean 1.95; and 810 ml:
      mean difference - 0.7 ml; range - 92.0 to 43.0 ml, std error mean 1.95).
      CONCLUSIONS: Accurate measurement of liquid ingredients is difficult to achieve
      even for trained professionals. The cumulative effect of many different liquid
      measurement errors (inappropriate jug type, inaccurate volume measured and poor
      technique) may lead to clinically important errors in the preparation of modular
      specialist feeds.

PMID- 27896085
TI  - Promoting psychological well-being in women with phenylketonuria: Pregnancy
      related stresses, coping strategies and supports.
AB  - OBJECTIVE: To explore the pregnancy-related stresses anticipated and experienced
      by women with phenylketonuria (PKU) and the coping strategies and supports
      utilised or anticipated to be beneficial during pregnancy. METHODS: Thematic
      analysis of interview data from eight women with PKU in a cross-sectional,
      qualitative study. Five of the participants had never had a pregnancy but were
      planning to in the future, two participants had children, and one participant was
      pregnant. RESULTS: The central concern regarding pregnancy was achieving and
      maintaining the essential low Phe levels, in the context of the devastating
      effects of high levels. The Transactional Model of Stress and Coping was utilised
      to understand the coping strategies and supports utilised or anticipated to be
      beneficial during pregnancy. Similarities and differences between the women who
      had experienced pregnancy, and those who were planning a pregnancy in the future
      were evident in key coping strategies, with knowledge seeking, positive
      reappraisal, and reassurance seeking reported. Support from health professionals
      and other mothers with PKU was key for all women. Psychological support was
      identified as a resource perceived to be beneficial to promote psychological well
      being during pregnancy but not yet provided. CONCLUSION: Pregnancy is associated
      with significant stresses for women with PKU. Clinical implications of the
      findings include provision of psychological support.

PMID- 27896086
TI  - Differential hexosamine biosynthetic pathway gene expression with type 2
      diabetes.
AB  - The hexosamine biosynthetic pathway (HBP) culminates in the attachment of O
      linked beta-N-acetylglucosamine (O-GlcNAc) onto serine/threonine residues of
      target proteins. The HBP is regulated by several modulators, i.e. O-linked beta-N
      acetylglucosaminyl transferase (OGT) and beta-N-acetylglucosaminidase (OGA)
      catalyze the addition and removal of O-GlcNAc moieties, respectively; while flux
      is controlled by the rate-limiting enzyme glutamine:fructose-6-phosphate
      amidotransferase (GFPT), transcribed by two genes, GFPT1 and GFPT2. Since
      increased HBP flux is glucose-responsive and linked to insulin resistance/type 2
      diabetes onset, we hypothesized that diabetic individuals exhibit differential
      expression of HBP regulatory genes. Volunteers (n = 60; n = 20 Mixed Ancestry, n
      = 40 Caucasian) were recruited from Stellenbosch and Paarl (Western Cape, South
      Africa) and classified as control, pre- or diabetic according to fasting plasma
      glucose and HbA1c levels, respectively. RNA was purified from leukocytes isolated
      from collected blood samples and OGT, OGA, GFPT1 and GFPT2 expressions determined
      by quantitative real-time PCR. The data reveal lower OGA expression in diabetic
      individuals (P < 0.01), while pre- and diabetic subjects displayed attenuated OGT
      expression vs. controls (P < 0.01 and P < 0.001, respectively). Moreover, GFPT2
      expression decreased in pre- and diabetic Caucasians vs. controls (P < 0.05 and P
      < 0.01, respectively). We also found ethnic differences, i.e. Mixed Ancestry
      individuals exhibited a 2.4-fold increase in GFPT2 expression vs. Caucasians,
      despite diagnosis (P < 0.01). Gene expression of HBP regulators differs between
      diabetic and non-diabetic individuals, together with distinct ethnic-specific
      gene profiles. Thus differential HBP gene regulation may offer diagnostic utility
      and provide candidate susceptibility genes for different ethnic groupings.

PMID- 27896088
TI  - Metyrapone, an inhibitor of cytochrome oxidases, does not affect viability in a
      neuroblastoma cell model of bilirubin toxicity.
AB  - BACKGROUND: Unconjugated hyperbilirubinemia may cause brain damage in infants,
      and globally remains a source of neonatal morbidity and mortality. A significant
      inter-individual variability in vulnerability to bilirubin toxicity remains
      largely unexplained. An enzyme located in mitochondria oxidizes bilirubin. We
      hypothesized that inhibiting bilirubin oxidation in human neuronal cell cultures
      exposed to bilirubin would increase cell death. METHODS: The ability of
      mitochondrial membranes from CHP-212 human neuroblastoma cells to oxidize
      bilirubin was verified by spectrophotometry. Intact cells in culture were exposed
      to bilirubin (75 MUM) with or without metyrapone (250 MUM) for 24 h, stained with
      Annexin-V and Propidium iodide and analyzed for apoptosis and necrosis by flow
      cytometry. RESULTS: Bilirubin caused a significant reduction of viability, from
      84 +/- 2.0% (mean +/- SEM) vs 67 +/- 2.7% (p < 0.05), but adding metyrapone to
      the bilirubin-exposed cells did not further impact cell viability. Metyrapone
      alone did not influence cell viability. CONCLUSION: Herein we have shown that
      metyrapone does not increase cell death in neuroblastoma cells in culture exposed
      to bilirubin. Our results question the relationship between the oxidative
      mechanism evaluated by spectrophotometry and cell viability. Our findings add to
      the discussion on whether bilirubin oxidation represents a potentially important
      protective mechanism in neurons challenged by hyperbilirubinemia.

PMID- 27896087
TI  - Glutaric Aciduria type I and acute renal failure - Coincidence or causality?
AB  - Glutaric Aciduria type I (GA-I) is a rare organic acidemia, caused by mutations
      in the GCDH gene, and characterized by encephalopathic crises with neurological
      sequelae. We report herein a patient with GA-I who presented with severe acute
      renal failure requiring dialysis, following an acute diarrheal illness.
      Histopathological evaluation demonstrated acute tubular necrosis, and molecular
      diagnosis revealed the patient to be homozygous for a previously unreported
      mutation, p.E64D. As renal impairment is not part of the clinical spectrum
      typical to GA-I, possible associations of renal failure and the underlying inborn
      error of metabolism are discussed, including recent advancements made in the
      understanding of the renal transport of glutaric acid and its derivatives during
      metabolic disturbance in GA-I.

PMID- 27896089
TI  - ATP6V0A2 mutations present in two Mexican Mestizo children with an autosomal
      recessive cutis laxa syndrome type IIA.
AB  - Patients with ARCL-IIA harbor mutations in ATP6V0A2 that codes for an organelle
      proton pump. The ARCL-IIA syndrome characteristically presents a combined
      glycosylation defect affecting N-linked and O-linked glycosylations,
      differentiating it from other cutis laxa syndromes and classifying it as a
      Congenital Disorder of Glycosylation (ATP6V0A2-CDG). We studied two Mexican
      Mestizo patients with a clinical phenotype corresponding to an ARCL-IIA syndrome.
      Both patients presented abnormal transferrin (N-linked) glycosylation but Patient
      1 had a normal ApoCIII (O-linked) glycosylation profile. Mutational screening of
      ATP6V0A2 using cDNA and genomic DNA revealed in Patient 1 a previously reported
      homozygous nonsense mutation c.187C>T (p.R63X) associated with a novel clinical
      finding of a VSD. In Patient 2 we found a homozygous c.2293C>T (p.Q765X) mutation
      that had been previously reported but found that it also altered RNA processing
      generating a novel transcript not previously identified (r.2176_2293del;
      p.F726Sfs*10). This is the first report to describe Mestizo patients with
      molecular diagnosis of ARCL-IIA/ATP6V0A2-CDG and to establish that their
      mutations are the first to be found in patients from different regions of the
      world and with different genetic backgrounds.

PMID- 27896090
TI  - Comments on 'Infantile hypophosphatasia without bone deformities presenting with
      severe pyridoxine-resistant seizures' in Molecular Genetics and Metabolism' 2014
      Mar;111(3):404-7 by M.G. de Roo, N.G. Abeling, C.B. Majoie, A.M. Bosch, J.H.
      Koelman, J.M. Cobben, M. Duran, B.T. Poll-The.

PMID- 27896092
TI  - Enzyme replacement therapy and antibodies in late-onset Pompe disease.

PMID- 27896091
TI  - Clinical variability in neurohepatic syndrome due to combined mitochondrial DNA
      depletion and Gaucher disease.
AB  - A 1-year-old girl born to consanguineous parents presented with unexplained liver
      failure, leading to transplantation at 19 months. Subsequent partial splenectomy
      for persistent cytopenia showed the presence of foamy cells, and Gaucher disease
      was confirmed by homozygosity for the p.Leu483Pro mutation in the GBA gene. She
      was treated by enzyme replacement therapy (ERT). Clinical follow-up showed mild
      developmental delay, strabismus, nystagmus and oculomotor apraxia. Biochemical
      studies revealed multiple respiratory chain deficiencies and a mosaic pattern of
      deficient complex IV immunostaining in liver and fibroblast. Molecular analysis
      identified a mtDNA depletion syndrome due to the homozygous p.Pro98Leu mutation
      in MPV17. A younger sister unaffected by mtDNA depletion, presented with
      pancytopenia and hepatosplenomegaly. ERT for Gaucher disease resulted in visceral
      normalization without any neurological symptom. A third sister, affected by both
      conditions, had marked developmental delay, strabismus and ophthalmoplegia but no
      liver cirrhosis. In conclusion, intrafamilal variability occurs in MPV17-related
      disease. The combined pathological effect of Gaucher and mitochondrial diseases
      can negatively impact neurological and liver functions and influence the outcome
      in consanguineous families. The immunocytochemical staining of OXPHOS protein in
      tissues and cultured cells is a powerful tool revealing mosaic pattern of
      deficiency pointing to mtDNA-related mitochondrial disorders.

PMID- 27896093
TI  - Neonatal pulmonary hypertension in mitochondrial disorders due to TMEM70
      mutations.

PMID- 27896094
TI  - Concurrent non-ketotic hyperglycinemia and propionic acidemia in an eight year
      old boy.
AB  - This is the first reported case of a patient with both non-ketotic
      hyperglycinemia and propionic acidemia. At 2 years of age, the patient was
      diagnosed with non-ketotic hyperglycinemia by elevated glycine levels and
      mutations in the GLDC gene (paternal allele: c.1576_1577insC delT and
      c.1580delGinsCAA; p.S527Tfs*13, and maternal allele: c.1819G>A; p.G607S). At 8
      years of age after having been placed on ketogenic diet, he became lethargic and
      had severe metabolic acidosis with ketonuria. Urine organic acid analysis and
      plasma acylcarnitine profile were consistent with propionic acidemia. He was
      found to have an apparently homozygous mutation in the PCCB gene: c.49C>A;
      p.Leu17Met. The patient was also treated with natural protein restriction,
      carnitine, biotin, and thiamine and had subjective and biochemical improvement.

PMID- 27896095
TI  - Residual OCTN2 transporter activity, carnitine levels and symptoms correlate in
      patients with primary carnitine deficiency.
AB  - BACKGROUND: The prevalence of primary carnitine deficiency (PCD) in the Faroe
      Islands is the highest reported in the world (1:300). Serious symptoms related to
      PCD, e.g. sudden death, have previously only been associated to the c.95A >
      G/c.95A > G genotype in the Faroe Islands. We report and characterize novel
      mutations associated with PCD in the Faroese population and report and compare
      free carnitine levels and OCTN2 transport activities measured in fibroblasts from
      PCD patients with different genotypes. METHODS: Genetic analyses were used to
      identify novel mutations, and carnitine uptake analyses in cultured skin
      fibroblasts from selected patients were used to examine residual OCTN2
      transporter activities of the various genotypes. RESULTS: Four different
      mutations, including the unpublished c.131C > T (p.A44V), the novel splice
      mutation c.825-52G > A and a novel risk-haplotype (RH) were identified in the
      Faroese population. The two most prevalent genotypes were c.95A > G/RH (1:600)
      and c.95A > G/c.95A > G (1:1300). Patients homozygous for the c.95A > G mutation
      had both the significantly (p < 0.01) lowest mean free carnitine level at 2.03
      (SD 0.66) MUmol/L and lowest residual OCTN2 transporter activity (4% of normal).
      There was a significant positive correlation between free carnitine levels and
      residual OCTN2 transporter activities in PCD patients (R2 = 0.430, p < 0.01).
      CONCLUSION: There was a significant positive correlation between carnitine levels
      and OCTN2 transporter activities. The c.95A > G/c.95A > G genotype had the
      significantly lowest mean free carnitine level and residual OCTN2 transporter
      activity.

PMID- 27896096
TI  - Peripheral leukocyte anomaly detected with routine automated hematology analyzer
      sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid
      storage disease with myopathy/triglyceride deposit cardiomyovasculopathy.
AB  - Adipose triglyceride lipase (ATGL) deficiency manifesting neutral lipid storage
      disease with myopathy/triglyceride deposit cardiomyovasculopathy presents
      distinct fat-containing vacuoles known as Jordans' anomaly in peripheral
      leucocytes. To develop an automatic notification system for Jordans' anomaly in
      ATGL-deficient patients, we analyzed circulatory leukocyte scattergrams on
      automated hematology analyzer XE-5000. The BASO-WX and BASO-WY values were found
      to be significantly higher in patients than those in non-affected subjects. The
      two parameters measured by automated hematology analyzer may be expected to
      provide an important diagnostic clue for homozygous ATGL deficiency.

PMID- 27896097
TI  - Female adipocyte androgen synthesis and the effects of insulin.
AB  - The metabolic syndrome is a cluster of metabolic disorders characterized by
      insulin resistance and hyperinsulinaemia, and its presence can increase the risk
      of cardiovascular disease significantly. The metabolic syndrome is associated
      with increased circulating androgen levels in women, which may originate from the
      ovaries and adrenal glands. Adipocytes are also able to synthesise steroid
      hormones, and this output has been hypothesised to increase with elevated insulin
      plasma concentrations. However, the contribution of the adipocytes to the
      circulating androgen levels in women with metabolic syndrome is limited and the
      effects of insulin are not fully understood. The aim of this study was to
      investigate the presence of steroid precursors and synthetic enzymes in human
      adipocyte biopsies as markers of possible adipocyte androgen synthesis. We
      examined pre and mature adipocytes taken from tissue biopsies of abdominal
      subcutaneous adipose tissue of participating women from the Department of
      Obstetrics and Gynaecology, of the Royal Derby Hospital. The results showed the
      potential for localised adipocyte androgen synthesis through the presence of the
      androgen precursor progesterone, as well as the steroid-converting enzyme 17alpha
      hydroxylase. Furthermore, we found the controlled secretion of androstenedione in
      vitro and that insulin treatment caused levels to increase. Continued examination
      of a localised source of androgen production is therefore of clinical relevance
      due to its influence on adipocyte metabolism, its negative impact on female
      steroidogenic homeostasis, and the possible aggravation this may have when
      associated to obesity and obesity related metabolic abnormalities such as
      hyperinsulinaemia.

PMID- 27896098
TI  - Disease-associated marked hyperalphalipoproteinemia.
AB  - Marked hyperalphalipoproteinemia (HAL) is a heterogeneous syndrome. To clarify
      the pathophysiological significance of HAL, we compared clinical profiles between
      marked HAL subjects with and without cholesteryl ester transfer protein (CETP)
      deficiency. CETP deficiency was associated with cardiovascular diseases and
      strokes in the HAL population, particularly in female. HAL women without CETP
      deficiency tended to have higher prevalence with cancer history. HAL may not
      always be a longevity marker, but be sometimes accompanied with pathological
      conditions.

PMID- 27896099
TI  - Natural history of motor neuron disease in adult onset GM2-gangliosidosis: A case
      report with 25 years of follow-up.
AB  - An adult with Sandhoff disease presented with pure lower motor neuron phenotype.
      Twenty years later, he showed signs of upper motor neuron involvement. 25 years
      from the onset, his muscle weakness slightly worsened but he was fully
      independent in activities of daily living. GM2-gangliosidosis can manifest as a
      motor neuron disease with a slowly progressive course. The correct knowledge of
      the natural history can be really important to achieve the diagnosis, design new
      therapies and evaluate clinical trials.

PMID- 27896100
TI  - Identification of three novel mutations by studying the molecular genetics of
      Maple Syrup Urine Disease (MSUD) in the Lebanese population.
AB  - Maple Syrup Urine Disease (MSUD) is a genetically heterogeneous metabolic
      disorder that is transmitted in an autosomal recessive manner. According to
      clinical data, MSUD prevalence in Lebanon is expected to be higher than the
      International prevalence because of consanguineous marriage. Novel mutations are
      still getting detected by using DNA sequencing for mutation analysis in MSUD
      patients. In the current study, we have extracted DNA from Lebanese MSUD patients
      in order to amplify the exonic and flanking intronic regions of the genes
      implicated in MSUD (BCKDHA, BCKDHB, and DBT) and sequenced the resultant
      amplified products to assess the molecular genetics of MSUD in the Lebanese
      population studied. All of the mutations identified occurred in the homozygous
      state, which reflects the high rate of consanguineous marriage in Lebanon. In the
      current study, we have identified one previously cited mutation and three novel
      mutations not previously described in the scientific literature. The identified
      mutations were distributed as follows: three patients (60%) had two nucleotide
      substitutions in the DBT gene (c.224G>A and c.1430T>G), one patient (20%) had a
      gross deletion in the BCKDHA gene (c.488_1167+3del), and one patient (20%) had a
      small deletion in the BCKDHB gene (c.92_102del). The majority of the mutations
      identified in the Lebanese MSUD patients occurred in the DBT gene. Consanguineous
      marriage is a major risk factor for the prevalence of MSUD in Lebanon.

PMID- 27896101
TI  - Late onset Leigh syndrome mimicking central nervous system vasculitis.

PMID- 27896102
TI  - Frequency of de novo mutations in Japanese patients with Fabry disease.
AB  - We examined alpha-galactosidase A (GLA) gene mutations in 74 Japanese families
      with Fabry disease (FD) to determine the frequency of de novo mutations. In 5 of
      74 families (6.8%), the probands had no positive family histories and were
      diagnosed as de novo because their parents had no mutations in GLA gene. The
      parents of Fabry patients do not necessarily have mutations in GLA gene which is
      an important consideration in genetic counseling for FD.

PMID- 27896103
TI  - Plasma mutant alpha-galactosidase A protein and globotriaosylsphingosine level in
      Fabry disease.
AB  - Fabry disease is an X-linked genetic disorder characterized by deficient activity
      of alpha-galactosidase A (GLA) and accumulation of glycolipids, and various GLA
      gene mutations lead to a wide range of clinical phenotypes from the classic form
      to the later-onset one. To investigate the biochemical heterogeneity and
      elucidate the basis of the disease using available clinical samples, we measured
      GLA activity, GLA protein and accumulated globotriaosylsphingosine (Lyso-Gb3), a
      biomarker of this disease, in plasma samples from Fabry patients. The analysis
      revealed that both the enzyme activity and the protein level were apparently
      decreased, and the enzyme activity was well correlated with the protein level in
      many Fabry patients. In these cases, a defect of biosynthesis or excessive
      degradation of mutant GLAs should be involved in the pathogenesis, and the
      residual protein level would determine the accumulation of Lyso-Gb3 and the
      severity of the disease. However, there are some exceptional cases, i.e., ones
      harboring p.C142Y, p.R112H and p.M296I, who exhibit a considerable amount of GLA
      protein. Especially, a subset of Fabry patients with p.R112H or p.M296I has been
      attracted interest because the patients exhibit almost normal plasma Lyso-Gb3
      concentration. Structural analysis revealed that C142Y causes a structural change
      at the entrance of the active site. It will lead to a complete enzyme activity
      deficiency, resulting in a high level of plasma Lyso-Gb3 and the classic Fabry
      disease. On the other hand, it is thought that R112H causes a relatively large
      structural change on the molecular surface, and M296I a small one in a restricted
      region from the core to the surface, both the structural changes being far from
      the active site. These changes will cause not only partial degradation but also
      degeneration of the mutant GLA proteins, and the degenerated enzymes exhibiting
      small and residual activity remain and probably facilitate degradation of Lyso
      Gb3 in plasma, leading to the later-onset phenotype. The results of this
      comprehensive analysis will be useful for elucidation of the basis of Fabry
      disease.

PMID- 27896104
TI  - Novel method to characterize CYP21A2 in Florida patients with congenital adrenal
      hyperplasia and commercially available cell lines.
AB  - Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder and
      affects approximately 1 in 15,000 births in the United States. CAH is one of the
      disorders included on the Newborn Screening (NBS) Recommended Uniform Screening
      Panel. The commonly used immunological NBS test is associated with a high false
      positive rate and there is interest in developing second-tier assays to increase
      screening specificity. Approximately 90% of the classic forms of CAH, salt
      wasting and simple virilizing, are due to mutations in the CYP21A2 gene. These
      include single nucleotide changes, insertions, deletions, as well as chimeric
      genes involving CYP21A2 and its highly homologous pseudogene CYP21A1P. A novel
      loci-specific PCR approach was developed to individually amplify the CYP21A2
      gene, the nearby CYP21A1P pseudogene, as well as any 30 kb deletion and gene
      conversion mutations, if present, as single separate amplicons. Using
      commercially available CAH positive specimens and 14 families with an affected
      CAH proband, the single long-range amplicon approach demonstrated higher
      specificity as compared to previously published methods.

PMID- 27896105
TI  - Retrospective TREC testing of newborns with Severe Combined Immunodeficiency and
      other primary immunodeficiency diseases.
AB  - In Manitoba, Canada, the overall incidence of Severe Combined Immunodeficiency
      (SCID) is three-fold higher than the national average, with SCID overrepresented
      in two population groups: Mennonites and First Nations of Northern Cree
      ancestries. T-cell receptor excision circle (TREC) assay is being used
      increasingly for neonatal screening for SCID in North America. However, the
      majority of SCID patients in Manitoba are T-cell-positive. Therefore it is likely
      that the TREC assay will not identify these infants. The goal of this study was
      to blindly and retrospectively perform TREC analysis in confirmed SCID patients
      using archived Guthrie cards. Thirteen SCID patients were tested: 5 T-negative
      SCID (3 with adenosine deaminase deficiency, 1 with CD3delta deficiency, and 1
      unclassified) and 8 T-positive SCID (5 with zeta chain-associated protein kinase
      (ZAP70) deficiency and 3 with inhibitor of kappa light polypeptide gene enhancer
      in B-cells, kinase beta (IKKbeta) deficiency). As a non-SCID patient group, 5
      Primary Immunodeficiency Disease (PID) patients were studied: 1 T-negative PID
      (cartilage-hair hypoplasia) and 4 T-positive PID (2 common immune deficiency
      (CID), 1 Wiskott-Aldrich syndrome, and 1 X-linked lymphoproliferative disease).
      Both patient groups required hematopoietic stem cell transplantation. In
      addition, randomly-selected de-identified controls (n = 982) were tested.
      Results: all T-negative SCID and PID had zero TRECs. Low-TRECs were identified in
      2 ZAP70 siblings, 1 CID patient as well as 5 preterm, 1 twin, and 4 de-identified
      controls. Conclusions: TREC method will identify T-negative SCID and T-negative
      PID. To identify other SCID babies, newborn screening in Manitoba must include
      supplemental targeted screening for ethnic-specific mutations.

PMID- 27896106
TI  - Parental knowledge reduces long term anxiety induced by false-positive test
      results after newborn screening for cystic fibrosis.
AB  - BACKGROUND: False-positive screening results in newborn screening for cystic
      fibrosis may lead to parental stress, family relationship problems and a changed
      perception of the child's health. AIM OF THE STUDY: To evaluate whether parental
      anxiety induced by a false positive screening result disappears after six months
      and to assess whether a special program to inform parents prior and during the
      screening procedure prevents or diminishes parental anxiety. METHODS: Prospective
      controlled study assessing the long term effects of false-positive test results
      of newborn screening for cystic fibrosis (NBSCF) on parental anxiety and stress
      by means of questionnaires sent to parents of 106 infants with a false positive
      newborn screening test and 318 randomly selected infants with a true negative
      screening test. Additionally we interviewed 25 parents of the false-positive
      group. RESULTS: Parents showed negative feelings after being informed about the
      positive screening test result. After confirmation that their child was healthy
      and not suffering from CF, most parents felt reassured. After six months no
      difference in anxiety levels between both groups of parents was found. Well
      informed parents in the false positive group experienced less stress.
      CONCLUSIONS: A positive screening test result induces parental anxiety but false
      positive test results in NBSCF do not seem to cause long-term anxiety. Well
      informed parents show lower stress and anxiety levels.

PMID- 27896107
TI  - Newborn screening for dihydrolipoamide dehydrogenase deficiency: Citrulline as a
      useful analyte.
AB  - Dihydrolipoamide dehydrogenase deficiency, also known as maple syrup urine
      disease (MSUD) type III, is caused by the deficiency of the E3 subunit of
      branched chain alpha-ketoacid dehydrogenase (BCKDH), alpha-ketoglutarate
      dehydrogenase (alphaKGDH), and pyruvate dehydrogenase (PDH). DLD deficiency
      variably presents with either a severe neonatal encephalopathic phenotype or a
      primarily hepatic phenotype. As a variant form of MSUD, it is considered a core
      condition recommended for newborn screening. The detection of variant MSUD forms
      has proven difficult in the past with no asymptomatic DLD deficiency patients
      identified by current newborn screening strategies. Citrulline has recently been
      identified as an elevated dried blood spot (DBS) metabolite in symptomatic
      patients affected with DLD deficiency. Here we report the retrospective DBS
      analysis and second-tier allo-isoleucine testing of 2 DLD deficiency patients. We
      show that an elevated citrulline and an elevated allo-isoleucine on second-tier
      testing can be used to successfully detect DLD deficiency. We additionally
      recommend that DLD deficiency be included in the "citrullinemia/elevated
      citrulline" ACMG Act Sheet and Algorithm.

PMID- 27896108
TI  - Association of genetic variants of the incretin-related genes with quantitative
      traits and occurrence of type 2 diabetes in Japanese.
AB  - BACKGROUND: None of the high frequency variants of the incretin-related genes has
      been found by genome-wide association study (GWAS) for association with
      occurrence of type 2 diabetes in Japanese. However, low frequency and rare and/or
      high frequency variants affecting glucose metabolic traits remain to be
      investigated. METHOD: We screened all exons of the incretin-related genes (GCG,
      GLP1R, DPP4, PCSK1, GIP, and GIPR) in 96 patients with type 2 diabetes and
      investigated for association of genetic variants of these genes with quantitative
      metabolic traits upon test meal with 38 young healthy volunteers and with the
      occurrence of type 2 diabetes in Japanese subjects comprising 1303 patients with
      type 2 diabetes and 1014 controls. RESULT: Two mutations of GIPR, p.Thr3Alafsx21
      and Arg183Gln, were found only in patients with type 2 diabetes, and both of them
      were treated with insulin. Of ten tagSNPs, we found that risk allele C of SNP393
      (rs6235) of PCSK1 was nominally associated with higher fasting insulin and HOMA-R
      (P = 0.034 and P = 0.030), but not with proinsulin level, incretin level or BMI.
      The variant showed significant association with occurrence of type 2 diabetes
      after adjustment for age, sex, and BMI (P = 0.0043). CONCLUSION: Rare variants of
      GIPR may contribute to the development of type 2 diabetes, possibly through
      insulin secretory defects. Furthermore, the genetic variant of PCSK1 might
      influence glucose homeostasis by altered insulin resistance independently of BMI,
      incretin level or proinsulin conversion, and may be associated with the
      occurrence of type 2 diabetes in Japanese.

PMID- 27896109
TI  - Somatic mosaicism for a novel PDHA1 mutation in a male with severe pyruvate
      dehydrogenase complex deficiency.
AB  - Pyruvate dehydrogenase complex (PDC) deficiencies are mostly due to mutations in
      the X-linked PDHA1 gene. Males with hemizygous PDHA1 mutations are clinically
      more severely affected, while those with mosaic PDHA1 mutations may manifest
      milder phenotypes. We report a patient harboring a novel, mosaic missense PDHA1
      mutation, c.523G > A (p.A175T), with a severe clinical presentation of congenital
      microcephaly, significant brain abnormalities, persistent seizures, profound
      developmental delay, and failure to thrive. We review published cases of PDHA1
      mosaicism.

PMID- 27896110
TI  - Whole exome sequencing reveals compound heterozygous mutations in SLC19A3 causing
      biotin-thiamine responsive basal ganglia disease.
AB  - Biotin-thiamine responsive basal ganglia disease (BTBGD) is a rare metabolic
      condition caused by mutations in the SLC19A3 gene. BTBGD presents with
      encephalopathy and significant disease progression when not treated with biotin
      and/or thiamine. We present a patient of Mexican and European ancestry diagnosed
      with BTBGD found to have compound heterozygous frameshift mutations, one novel.
      Our report adds to the genotype-phenotype correlation, highlighting the clinical
      importance of considering SLC19A3 gene defects as part of the differential
      diagnosis for Leigh syndrome.

PMID- 27896111
TI  - Development of catecholamine and cortisol stress responses in zebrafish.
AB  - Both adrenal catecholamines and steroids are known to be involved in the stress
      response, immune function, blood pressure and energy homeostasis. The response to
      stress is characterized by the activation of the hypothalamus-pituitary-adrenal
      (HPA) axis and the sympathetic-adrenomedullary system, though the correlation
      with activation and development is not well understood. We evaluated the stress
      response of both cortisol and catecholamines during development in zebrafish.
      Zebrafish at two different stages of development were stressed in one of two
      different ways and cortisol and catecholamine were measured. Cortisol was
      measured by enzyme immune assay and catecholamine was measured by ELISA. Our
      results show that stress responses are delayed until after the synthesis of both
      cortisol and catecholamines. These observations suggest that the development of
      HPA axis may be required for the acquisition of the stress response for cortisol
      and catecholamines.

PMID- 27896112
TI  - Effects of intracerebroventricular administration of 2-hydroxypropyl-beta
      cyclodextrin in a patient with Niemann-Pick Type C disease.
AB  - Niemann-Pick Type C disease (NPC) is an autosomal recessive lysosomal storage
      disorder characterized by progressive neurological deterioration. Previously, we
      reported that intravenous administration of 2-hydroxypropyl-beta-cyclodextrin
      (HPB-CD) in two patients with NPC had only partial and transient beneficial
      effects on neurological function. The most likely reason for HPB-CD not
      significantly improving the neurological deficits of NPC is its inability to
      cross the blood-brain barrier. Herein, we describe the effects of intrathecal HPB
      CD in an eight-year-old patient with a perinatal onset of NPC, administered
      initially at a dose of 10 mg/kg every other week and increased up to 10 mg/kg
      twice a week. Clinically, the patient maintained residual neurological functions
      for two years, at which time nuclear magnetic resonance spectroscopy showed a
      decreased choline to creatine ratio and increased N-acetylaspartate to creatine
      ratio, and positron emission tomography revealed increased standardized uptake
      values. Total-tau in the cerebrospinal fluid (CSF) was also decreased after two
      years. No adverse effects were observed over the course of treatment. The CSF
      concentrations of HPB-CD during the distribution phase after the injections were
      comparable with those at which HPB-CD could normalize cellular cholesterol
      abnormality in vitro. Further studies are necessary to elucidate the mechanisms
      of action of HPB-CD in NPC, and to determine the optimal dose and intervals of
      HPB-CD injection.

PMID- 27896113
TI  - Identification of 17 novel mutations in 40 Argentinean unrelated families with
      mucopolysaccharidosis type II (Hunter syndrome).
AB  - Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disorder
      caused by deficiency of the enzyme iduronate-2-sulfatase (IDS). The human IDS
      gene is located in chromosome Xq28. This is the first report of genotype and
      phenotype characterization of 49 Hunter patients from 40 families of Argentina.
      Thirty different alleles have been identified, and 57% were novel. The frequency
      of de novo mutations was 10%. Overall, the percentage of private mutations in our
      series was 75%.

PMID- 27896114
TI  - Mitochondrial damage and cholesterol storage in human hepatocellular carcinoma
      cells with silencing of UBIAD1 gene expression.
AB  - Heterozygous mutations in the UBIAD1 gene cause Schnyder corneal dystrophy
      characterized by abnormal cholesterol and phospholipid deposits in the cornea.
      Ubiad1 protein was recently identified as Golgi prenyltransferase responsible for
      biosynthesis of vitamin K2 and CoQ10, a key protein in the mitochondrial electron
      transport chain. Our study shows that silencing UBIAD1 in cultured human
      hepatocellular carcinoma cells causes dramatic morphological changes and
      cholesterol storage in the mitochondria, emphasizing an important role of UBIAD1
      in mitochondrial function.

PMID- 27896115
TI  - Right frontal lobe encephalomalacia in an adult propionic acidemia patient with
      neuropsychiatric manifestations.

PMID- 27896116
TI  - Fabry disease: Evidence for a regional founder effect of the GLA gene mutation
      30delG in Brazilian patients.
AB  - The Fabry disease is caused by mutations in the gene (GLA) that encodes the
      enzyme alpha-galactosidase A (alpha-Gal A). More than 500 pathologic variants of
      GLA have already been described, most of them are family-specific. In southern
      Brazil, a frequent single-base deletion (GLA 30delG) was identified among four
      families that do not recognize any common ancestral. In order to investigate the
      history of this mutation (investigate the founder effect, estimate the mutation
      age and the most likely source), six gene-flanking microsatellite markers of the
      X chromosome on the mutation carriers and their parents, 150 individuals from the
      same population and 300 individuals that compose the Brazilian parental
      populations (Europeans, Africans and Native Americans) were genotyped. A common
      haplotype to the four families was identified and characterized as founder. The
      age was estimated with two statistics software (DMLE 2.2 and ESTIAGE) that agreed
      with 11 to 12 generations old. This result indicates that the mutation GLA 30delG
      was originated from a single event on the X chromosome of a European immigrant,
      during the southern Brazil colonization between 1710 and 1740.

PMID- 27896117
TI  - Cardiac disease as the presenting feature of mucopolysaccharidosis type IIIA: A
      case report.
AB  - Severe cardiac involvement is a common feature of mucopolysaccharidoses (MPS),
      but occurs only rarely in MPS III (Sanfilippo syndrome). We report herein a case
      of MPS III-A having cardiac involvement as its first manifestation. Analysis of
      the SGSH gene showed homozygosity for the novel mutation p.G80V. We propose that
      MPS disorders, including MPS III-A, should be included in the differential
      diagnosis of every case of cardiomyopathy presenting during the first year of
      life.

PMID- 27896119
TI  - Novel OPA1 mutation featuring spastic paraparesis and intestinal dysmotility.
AB  - A 58-year-old man with optic atrophy, spastic paraparesis, axonal sensorimotor
      peripheral neuropathy and intestinal dysmotility harbors a novel heterozygous
      missense mutation in the mitochondrial import signal peptide of OPA1. The case
      underscores the role of OPA1 in the pathogenesis of spastic paraparesis, so far
      reported only in very few cases, and it adds intestinal dysmotility to the
      spectrum of adult-onset clinical manifestation of OPA1-associated disease.

PMID- 27896118
TI  - Expanding the spectrum of HEXA mutations in Indian patients with Tay-Sachs
      disease.
AB  - Tay-Sachs disease is an autosomal recessive neurodegenerative disorder occurring
      due to impaired activity of beta-hexosaminidase-A (EC 3.2.1.52), resulting from
      the mutation in HEXA gene. Very little is known about the molecular pathology of
      TSD in Indian children except for a few mutations identified by us. The present
      study is aimed to determine additional mutations leading to Tay-Sachs disease in
      nine patients confirmed by the deficiency of beta-hexosaminidase-A (< 2% of total
      hexosaminidase activity for infantile patients) in leucocytes. The enzyme
      activity was assessed by using substrates 4-methylumbelliferyl-N-acetyl-beta-d
      glucosamine and 4-methylumbelliferyl-N-acetyl-beta-d-glucosamine-6-sulfate for
      total-hexosaminidase and hexosaminidase-A respectively, and heat inactivation
      method for carrier detection. The exons and exon-intron boundaries of the HEXA
      gene were bi-directionally sequenced on an automated sequencer. 'In silico'
      analyses for novel mutations were carried out using SIFT, Polyphen2 and
      MutationT@ster software programs. The structural study was carried out by UCSF
      Chimera software using the crystallographic structure of beta-hexosaminidase-A
      (PDB-ID: 2GJX) as the template. Our study identified four novel mutations in
      three cases. These include a compound heterozygous missense mutation c.524A>C
      (D175A) and c.805G>C (p.G269R) in one case; and one small 1 bp deletion c.426delT
      (p.F142LfsX57) and one splice site mutation c.459+4A>C in the other two cases
      respectively. None of these mutations were detected in 100 chromosomes from
      healthy individuals of the same ethnic group. Three previously reported missense
      mutations, (i) c.532C>T (p.R178C), (ii) c.964G>T (p.D322Y), and (iii) c.1385A>T
      (p.E462V); two nonsense mutations (i) c.709C>T (p.Q237X) and (ii) c.1528C>T
      (p.R510X), one 4 bp insertion c.1277_1278insTATC (p.Y427IfsX5) and one splice
      site mutation c.459+5G>A were also identified in six cases. We observe from this
      study that novel mutations are more frequently observed in Indian patients with
      Tay-Sachs disease with clustering of ~ 73% of disease causing mutations in exons
      5 to 12. This database can be used for a carrier rate screening in the larger
      population of the country.

PMID- 27896121
TI  - A SUCLG1 mutation in a patient with mitochondrial DNA depletion and congenital
      anomalies.
AB  - Defects in two subunits of succinate-CoA ligase encoded by the genes SUCLG1 and
      SUCLA2 have been identified in mitochondrial DNA (mtDNA) depletion syndromes.
      Patients generally present with encephalomyopathy and mild methylmalonic acidemia
      (MMA), however mutations in SUCLG1 normally appear to result in a more severe
      clinical phenotype. In this report, we describe a patient with fatal infantile
      lactic acidosis and multiple congenital anomalies (MCAs) including renal and
      cardiac defects. Molecular studies showed a defective electron transport chain
      (ETC), mtDNA depletion, and a novel homozygous mutation in the SUCLG1 gene.
      Although our patient's clinical biochemical phenotype is consistent with a SUCLG1
      mutation, it is unclear whether the MCAs observed in our patient are a result of
      the SUCLG1 mutation or alterations in a second gene. An increasing number of
      reports have described MCAs associated with mitochondrial disorders and SUCLG1
      specifically. Additional studies such as whole exome sequencing will further
      define whether additional genes are responsible for the observed MCAs.

PMID- 27896120
TI  - Non-depleting anti-CD4 monoclonal antibody induces immune tolerance to ERT in a
      murine model of Pompe disease.
AB  - Approximately 35-40% of patients with classic infantile Pompe disease treated
      with enzyme replacement therapy (ERT) develop high, sustained antibody titers
      against the therapeutic enzyme alglucosidase alfa, which abrogates the treatment
      efficacy. Induction of antigen-specific immune tolerance would greatly enhance
      ERT for these patients. Here we show that a short-course treatment with non
      depleting anti-CD4 monoclonal antibody successfully induced long-term ERT
      specific immune tolerance in Pompe disease mice. Our data suggest an effective
      adjuvant therapy to ERT.

PMID- 27896122
TI  - Clinical and biochemical characterization of 3-hydroxyisobutyryl-CoA hydrolase
      (HIBCH) deficiency that causes Leigh-like disease and ketoacidosis.
AB  - 3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is an autosomal recessive
      disorder characterized by episodes of ketoacidosis and a Leigh-like basal ganglia
      disease, without high concentrations of pyruvate and lactate in the cerebrospinal
      fluid. Only 4 cases of HIBCH deficiency have been reported. However, clinical
      biochemical correlation in HIBCH deficiency by determining the detailed residual
      enzyme activities has not yet been elucidated. Here, we report a case of two
      Japanese siblings with HIBCH deficiency carrying a new homozygous missense
      mutation (c.287C > A, [p.A96D]) at the substrate-binding site. A transfection
      study using HIBCH expression vectors harboring wild type or 4 reported mutations,
      including the newly identified mutation (p.A96D, p.Y122C, p.G317E, and
      p.K74Lfs*13), revealed a correlation between residual HIBCH activities and the
      severity of the disease. All HIBCH mutants, except p.K74Lfs*13, showed residual
      enzyme activity and only the patient with p.K74Lfs*13 had congenital anomalies.
      p.G317E showed only low enzyme activity (~ 3%) of that of wild-type HIBCH.
      Although p.A96D had approximately 7 times higher enzyme activity than p.G317E,
      patients with p.A96D died during childhood. These findings are essential for
      clinical management, genetic counseling, and specific meal and concomitant drug
      considerations as part of the treatment for patients with HIBCH deficiency.

PMID- 27896123
TI  - Development of a fluorometric microtiter plate based enzyme assay for MPS IVA
      (Morquio type A) using dried blood spots.
AB  - Mucopolysaccharidosis type IVA or Morquio type-A disease is a hereditary
      lysosomal storage disorder caused by deficient activity of the lysosomal enzyme N
      acetylgalactosamine-6-sulfate sulfatase (GALNS). The disease is caused by
      lysosomal accumulation of unprocessed glycosaminoglycans (GAGs) that manifests
      with severe to mild skeletal and cardiopulmonary abnormalities. We have developed
      a modified microtiter plate-based enzyme activity assay using dried blood spots
      and a fluorescent substrate for measuring specific GALNS activity to identify
      patients with MPS IVA.

PMID- 27896124
TI  - Development of a fluorometric microtiter plate-based enzyme assay for
      arylsulfatase B (MPS VI) using dried blood spots.
AB  - Mucopolysaccharidosis type VI or Maroteaux-Lamy syndrome is an autosomal
      recessive lysosomal storage disorder caused by deficiency of arylsulfatase B (ARS
      B) enzyme activity. It results in mild to severe multi-organ system failure from
      accumulation of undigested glycosaminoglycans (GAGs); dermatan sulfate and
      chondroitin-4-sulfate. We have developed a single-step enzyme assay using a
      fluorescent substrate and dried blood spots to measure ARS-B activity to identify
      disease patients. This assay is robust, reproducible, specific and convenient to
      perform.

PMID- 27896125
TI  - Genotypic and bioinformatic evaluation of the alpha-l-iduronidase gene and
      protein in patients with mucopolysaccharidosis type I from Colombia, Ecuador and
      Peru.
AB  - Mucopolysaccharidosis type I (MPSI) is a rare autosomal recessive disorder caused
      by mutations in the gene encoding the lysosomal enzyme alpha-l-iduronidase
      (IDUA), which is instrumental in the hydrolysis of the glycosaminoglycans,
      dermatan and heparan sulfate. The accumulation of unhydrolyzed glycosaminoglycans
      leads to pathogenesis in multiple tissue types, especially those of skeletal,
      nervous, respiratory, cardiovascular, and gastrointestinal origin. Although
      molecular diagnostic tools for MPSI have been available since the identification
      and characterization of the IDUA gene in 1992, Colombia, Ecuador, and Peru have
      lacked such methodologies. Therefore, the mutational profile of the IDUA gene in
      these countries has largely been unknown. The goal of this study was to
      characterize genotypes in 14 patients with MPSI from Colombia, Ecuador, and Peru.
      The most common mutation found at a frequency of 42.8% was W402X. Six patients
      presented with seven novel mutations, a high novel mutational rate in this
      population (32%). These novel mutations were validated using bioinformatic
      techniques. A model of the IDUA protein resulting from three of the novel
      missense mutations (Y625C, P385L, R621L) revealed that these mutations alter
      accessible surface area values, thereby reducing the accessibility of the enzyme
      to its substrates. This is the first characterization of the mutational profile
      of the IDUA gene in patients with MPSI in Colombia, Ecuador, and Peru. The
      findings contribute to our understanding of IDUA gene expression and IDUA enzyme
      function, and may help facilitate early and improved diagnosis and management for
      patients with MPSI.

PMID- 27896126
TI  - A novel mutation in the leptin gene (W121X) in an Egyptian family.
AB  - Congenital leptin deficiency is a rare recessively inherited condition due to
      homozygous mutations in the LEP gene. To date, only nine mutations have been
      identified in the LEP gene (p.L72S, p.N103K, p.R105W, p.H118L, p.S141C,
      c.104_106delTCA, c.135del3bp, c.398delG and c.481_482delCT). In this study we
      present a novel homozygous nonsense mutation (W121X) in LEP in a twelve year old
      obese male and his severely obese sister. As this disorder is treatable with
      recombinant leptin, it is intriguing to report a novel homozygous nonsense
      mutation in LEP in two obese children of consanguineous parents. These patients
      showed features in accordance with leptin deficiency.

PMID- 27896128
TI  - Overweight and obesity in PKU: The results from 8 centres in Europe and Turkey.
AB  - INTRODUCTION: In PKU there is little data comparing the prevalence of overweight
      and obesity in different countries. The aim of this cross sectional study was to
      evaluate prevalence data from different PKU treatment centres in Europe and
      Turkey. SUBJECTS AND METHODS: In children, body mass index (BMI) and z scores and
      in adults BMI were calculated in 947 patients (783 children aged < 19 years; 164
      adults aged >= 19 years) with PKU from centres in Europe and Turkey (Ankara,
      Birmingham, Brussels, Copenhagen, Groningen, Madrid, Munich and Porto). RESULTS:
      In adults with PKU, 83% of centres (n = 5/6) had less overweight than the general
      populations but 83% (n = 5/6) had a higher rate of female obesity. In childhood,
      all centres reported obesity rates within or similar to local population ranges
      in boys but in 57% (n = 4/7) of centres a higher rate of obesity in girls. The
      percentage of overweight and obesity increased with age. DISCUSSION: In PKU, it
      is clear from a number of treatment centres that women and girls with PKU appear
      particularly vulnerable to excess weight gain and it is important that female
      weight gain is closely monitored and individual strategies introduced to prevent
      excess weight gain. Overall, in PKU there is a need to understand better the food
      patterns and activity levels of patients.

PMID- 27896127
TI  - Can APOE and MTHFR polymorphisms have an influence on the severity of
      cardiovascular manifestations in Italian Pseudoxanthoma elasticum affected
      patients?
AB  - BACKGROUND: The clinical phenotype of Pseudoxanthoma elasticum (PXE) affected
      patients, although progressive with age, is very heterogeneous, even in the
      presence of identical ABCC6 mutations, thus suggesting the occurrence of modifier
      genes. Beside typical skin manifestations, the cardiovascular (CV) system, and
      especially the peripheral vasculature, is frequently and prematurely compromised.
      METHODS AND RESULTS: A cohort of 119 Italian PXE patients has been characterized
      for apolipoprotein E (APOE) and methylenetetrahydrofolate reductase (MTHFR) gene
      polymorphisms by PCR. The severity of the clinical phenotype has been quantified
      according to the Phenodex PXE International score system. Statistical analysis
      (chi2 test, odd ratio, regression analysis, analysis of variance) were done by
      GraphPad. Data demonstrate that the frequency of APOE alleles is similar in PXE
      patients and in healthy subjects and that the allelic variant E2 confers a
      protection against the age-related increase of CV manifestations. By contrast,
      PXE patients are characterized by high frequency of the MTHFR-T677T polymorphism.
      With age, CV manifestations in T677T, but also in C677T, patients are more severe
      than those associated with the C677C genotype. Interestingly, compound
      heterozygosity for C677T and A1298C polymorphisms is present in 70% of PXE
      patients. CONCLUSIONS: PXE patients may be screened for these polymorphisms in
      order to support clinicians for a better management of disease-associated CV
      complications.

PMID- 27896129
TI  - One-carbon cycle alterations induced by Dyrk1a dosage.
AB  - Hyperhomocysteinemia due to cystathionine beta synthase deficiency confers
      diverse clinical manifestations. It is characterized by elevated plasma
      homocysteine levels, a common amino acid metabolized by remethylation to
      methionine or transsulfuration to cysteine. We recently found a relationship
      between hepatic Dyrk1A protein expression, a serine/threonine kinase involved in
      signal transduction in biological processes, hepatic S-adenosylhomocysteine
      activity, and plasma homocysteine levels. We aimed to study whether there is also
      a relationship between Dyrk1a and cystathionine beta synthase activity. We used
      different murine models carrying altered gene coy numbers for Dyrk1a, and found a
      decreased cystathionine beta synthase activity in the liver of mice under
      expressing Dyrk1a, and an increased in liver of mice over-expressing Dyrk1a. For
      each model, a positive correlation was found between cystathionine beta synthase
      activity and Dyrk1a protein expression in the liver of mice, which was confirmed
      in a non-modified genetic context. The positive correlation found between liver
      Dyrk1a protein expression and CBS activity in modified and non-modified genetic
      context strengthens the role of this kinase in one carbon metabolism.

PMID- 27896130
TI  - Studies of the autoinhibitory segment comprising residues 31-60 of the prodomain
      of PCSK9: Possible implications for the mechanism underlying gain-of-function
      mutations.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density
      lipoprotein receptor (LDLR) at the cell surface and is internalized as a complex
      with the LDLR. In the acidic milieu of the sorting endosome, PCSK9 remains bound
      to the LDLR and prevents the LDLR from folding over itself to adopt a closed
      conformation. As a consequence, the LDLR fails to recycle back to the cell
      membrane. Even though it is the catalytic domain of PCSK9 that interacts with the
      LDLR at the cell surface, the structurally disordered segment consisting of
      residues 31-60 and which is rich in acidic residues, has a negative effect both
      on autocatalytic cleavage and on the activity of PCSK9 towards the LDLR. Thus,
      this unstructured segment represents an autoinhibitory domain of PCSK9. One may
      speculate that post-translational modifications within residues 31-60 may affect
      the inhibitory activity of this segment, and represent a mechanism for fine
      tuning the activity of PCSK9 towards the LDLR. Our data indicate that the
      inhibitory effect of this unstructured segment results from an interaction with
      basic residues of the catalytic domain of PCSK9. Mutations in the catalytic
      domain which involve charged residues, could therefore be gain-of-function
      mutations by affecting the positioning of this segment.

PMID- 27896131
TI  - Case report: 5 year follow-up of adult late-onset mitochondrial encephalomyopathy
      with lactic acid and stroke-like episodes (MELAS).
AB  - Mitochondrial encephalomyopathy with lactic acid and stroke-like episodes (MELAS)
      is a multisystem mitochondrial disorder that typically presents in childhood. We
      describe the follow-up of a patient who was diagnosed with late-onset MELAS at
      the age of 49. Her clinical course includes sensorineural hearing loss, seizures,
      and multiple episodes of stroke-like metabolic crises. Molecular genetic testing
      on whole blood revealed 31% heteroplasmy of a m.3243A > G variant in the mtDNA,
      the causative variant in approximately 80% of MELAS cases. The original
      diagnostic criteria for MELAS required the onset of stroke-like episodes prior to
      40 years of age but this case and others demonstrate that onset may be delayed in
      certain individuals. Therefore, MELAS should be included in the differential
      diagnosis of stroke-like episodes in patients of any age.

PMID- 27896132
TI  - Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in
      two siblings with infantile-onset Pompe disease treated in the symptomatic or pre
      symptomatic state.
AB  - Pompe disease is an autosomal recessive, lysosomal glycogen storage disease
      caused by acid alpha-glucosidase deficiency. Infantile-onset Pompe disease (IOPD)
      is the most severe form and is characterized by cardiomyopathy, respiratory
      distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally
      results in death within the first year of life. Enzyme replacement therapy (ERT)
      with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly
      improve the life expectancy of patients with IOPD. However, the efficacy of ERT
      in patients with IOPD is affected by the presence of symptoms and cross-reactive
      immunologic material (CRIM) status. We have treated two siblings with IOPD with
      ERT at different ages: the first was symptomatic and the second was asymptomatic.
      The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4
      months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days
      of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but
      bedridden, and requires 24-hour invasive ventilation due to gradually progressive
      muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac
      failure, respiratory distress, progressive muscle weakness, hepatomegaly and
      myopathic facial features were largely absent during the first 12 months of ERT.
      Her cardiac function and mobility were well-maintained for the first 3 years, and
      she had normal motor development. However, she developed progressive hearing
      impairment and muscle weakness after 3 years of ERT. Both siblings have had low
      anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated
      the treatment well. These results suggest that initiation of ERT during the pre
      symptomatic period can prevent and/or attenuate the progression of IOPD,
      including cardiomyopathy, respiratory distress, and muscle weakness for first
      several years of ERT. However, to improve the long-term efficacy of ERT for IOPD,
      new strategies for ERT for IOPD, e.g. modifying the enzyme to enhance uptake into
      skeletal muscle and/or to cross the blood brain barrier (BBB), will be required.

PMID- 27896133
TI  - Genital Self-mutilation Case in High-level Educated Person.
AB  - Self-mutilation is the deliberate direct injuring of body tissue, often done
      without suicidal intention. Genital self-mutilation is a very rare event and self
      harm of the penis, especially in the genital system is exceedingly rare.
      Generally, this kind of behavior is related to psychotic disorders but can
      sometimes be seen in non-psychotic people due to bizarre autoerotic acts, a
      desire for to change sex or religious beliefs that view sexual intercourse as a
      sin. Our case was the reported genital self-mutilation as a result of the bizarre
      sexual arousal of a young man who is employed as an architect.

PMID- 27896134
TI  - Robot-assisted Pyeloureterostomy in Bifid Renal Pelvis With Ureteropelvic
      Junction Obstruction of the Lower Moiety.
AB  - Duplications of the urinary collecting system and pyelo-ureteral junction
      obstruction (PUJO) are common, but the simultaneous presence of both anomalies is
      rarely encountered. In incomplete duplicated systems, PUJO usually affects the
      lower moiety. We present the case of a 5-year old boy with left bifid renal
      pelvis and hydronephosis of the lower moiety treated by robot-assisted
      pyeloureterostomy.

PMID- 27896135
TI  - Thrombus-like Tumor of Renal Cell Carcinoma Mimicking Transitional Cell Carcinoma
      of Kidney: A Case Report.
AB  - Renal cell carcinoma (RCC) is the most common malignancy of the kidney. It is not
      commonly form tumor thrombus in the ureter or renal pelvis. A 29-year-old woman
      presented with asymptomatic gross hematuria. Contrast CT study revealed a tumor
      suspected to be a Transitional Cell Carcinoma (TCC). However, tumor thrombus was
      found in the renal pelvis and ureter. We performed Nephroureterectomy, bladder
      cuff excision, and lymph node dissection, and the tumor was diagnosed
      histopathologically as RCC. We report a very rare case of thrombus-like tumor of
      renal cell carcinoma mimicking transitional cell carcinoma of kidney.

PMID- 27896136
TI  - Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction.
AB  - BACKGROUND: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is
      not known, and therefore the present study investigated mitochondrial defects, if
      any in cybrids created from patients and control population. METHODS: To
      investigate mitochondrial pathology in ADHD, cybrids cell lines were created from
      ADHD probands and controls by fusing their platelets with rho0-cells prepared
      from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress,
      mitochondrial membrane potential and morphology were evaluated employing
      oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and
      immunocytochemistry. HPLC-electrochemical detection, quantitative RT-PCR and Blue
      Native PAGE were employed respectively for assays of serotonin, mitochondrial
      ATPase 6/8 subunits levels and complex V activity. RESULTS: Significantly low
      cellular and mitochondrial respiration, ATPase6/8 transcripts levels,
      mitochondrial complex V activity and loss of mitochondrial membrane potential and
      elevated oxidative stress were observed in ADHD cybrids. Expression of monoamine
      oxidizing mitochondrial enzymes, MAO-A and MAO-B levels remained unaffected. Two
      fold increase in serotonin level was noted in differentiated cybrid-neurons.
      CONCLUSIONS: Since cybrids are shown to replicate mitochondrial defects seen in
      post-mortem brains, these observed defects in ADHD cybrids strongly suggest
      mitochondrial pathology in this disorder. GENERAL SIGNIFICANCE: Mitochondrial
      defects are detected in ADHD cybrids created from patients' platelets, implying
      bioenergetics crisis in the mitochondria could be a contributory factor for ADHD
      pathology and/or phenotypes.

PMID- 27896138
TI  - Making standards for quantitative real-time pneumococcal PCR.
AB  - Quantitative lytA PCR is often performed using in-house standards. We
      hypothesised equivalence when measuring a standard suspension of Streptococcus
      pneumoniae by colony-forming-units (CFU) or genome-copies. Median (IQR) ratio of
      CFU/genome-copies was 0.19 (0.1-1.2). Genome-copies were less variable than CFU,
      but the discrepancy between the methods highlights challenges with absolute
      quantification.

PMID- 27896137
TI  - Lymph node or perineural invasion is associated with low miR-15a, miR-34c and miR
      199b levels in head and neck squamous cell carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs or miRs) are post-transcriptional regulators of
      eukaryotic cells and knowledge of differences in miR levels may provide new
      approaches to diagnosis and therapy. METHODS: The present study measured the
      levels of nine miRs in head and neck squamous cell carcinomas (HNSCC) and
      determined whether clinical pathological features are associated with differences
      in miR levels. SET (I2PP2A) and PTEN protein levels were also measured, since
      their levels can be regulated by miR-199b and miR-21, respectively. Nine miRs
      (miR-15a, miR-21, miR-29b, miR-34c, miR-100, miR-125b, miR-137, miR-133b and miR
      199b) were measured by real time qRT-PCR in HNSCC samples from 32 patients and
      eight resection margins. SET (I2PP2A) and PTEN protein levels were estimated by
      immunohistochemistry in paired HNSCC tissues and their matched resection margins.
      RESULTS: In HNSCC, the presence of lymph node invasion was associated with low
      miR-15a, miR-34c and miR-199b levels, whereas the presence of perineural invasion
      was associated with low miR-199b levels. In addition, miR-21 levels were high
      whereas miR-100 and miR-125b levels were low in HNSCC compared to the resection
      margins. When HNSCC line HN12, with or without knockdown of SET, were transfected
      with miR-34c inhibitor or miR-34c mimic, the miR-34c inhibitor increased cell
      invasion capacity while miR-34c mimic decreased the cell invasion. CONCLUSIONS:
      We showed that the levels of specific miRs in tumor tissue can provide insight
      into the maintenance and progression of HNSCC. GENERAL SIGNIFICANCE: MiRNAs are
      up- or down-regulated during cancer development and progression; they can be
      prognosis markers and therapeutic targets in HNSCC.

PMID- 27896139
TI  - A novel approach for evaluating the performance of real time quantitative loop
      mediated isothermal amplification-based methods.
AB  - Molecular diagnostic measurements are currently underpinned by the polymerase
      chain reaction (PCR). There are also a number of alternative nucleic acid
      amplification technologies, which unlike PCR, work at a single temperature. These
      'isothermal' methods, reportedly offer potential advantages over PCR such as
      simplicity, speed and resistance to inhibitors and could also be used for
      quantitative molecular analysis. However there are currently limited mechanisms
      to evaluate their quantitative performance, which would assist assay development
      and study comparisons. This study uses a sexually transmitted infection
      diagnostic model in combination with an adapted metric termed isothermal doubling
      time (IDT), akin to PCR efficiency, to compare quantitative PCR and quantitative
      loop-mediated isothermal amplification (qLAMP) assays, and to quantify the impact
      of matrix interference. The performance metric described here facilitates the
      comparison of qLAMP assays that could assist assay development and validation
      activities.

PMID- 27896141
TI  - Characterization of non-classical quinolone resistance in Salmonella enterica
      serovar Typhi: Report of a novel mutation in gyrB gene and diagnostic challenges.
AB  - OBJECTIVE: To establish the relative importance of Salmonella enterica serovar
      Typhi with non-classical quinolone resistance. METHODS: Eight hundred and ninety
      one isolates of S. Typhi, isolated between 2004 and 2011, were tested for
      antibiotic susceptibility determination using disc diffusion and E-test. The
      mechanisms of fluoroquinolone resistance were studied in a sub-set of the NALS
      (nalidixic acid susceptible) isolates by wave nucleic acid fragment analysis of
      PCR products from gyrA, gyrB, parC and parE and from the plasmid borne
      determinants: qnrA,B,S; aac(6')-Ib-cr and qepA. To assess genetic relatedness
      multi-locus variable number tandem repeat analysis was carried out using five
      loci. RESULTS: Eighty isolates with a nalidixic acid MIC of <32 mg/L (NALS) and a
      ciprofloxacin MIC of >0.064 mg/L CIPI (ciprofloxacin reduced susceptibility) were
      found. In 36 NALS CIPI isolates two distinct genotypes were identified when
      compared with 16 susceptible controls: Group B (n = 34), mutation in gyrB at
      codon 464, NAL MIC of 3-12 mg/L and CIP MIC of 0.064-0.5 mg/L.; and Group C,
      mutation in gyrA at codon 83 (n = 2) NAL MIC of 16 mg/L and CIP MIC of 0.25-0.38
      mg/L. Group B isolates were found in different strain backgrounds as defined by
      MLVA. CONCLUSION: The use of nalidixic acid to screen for reduced susceptibility
      to fluoroquinolones in S. Typhi misses CIPI-NALS isolates, an established
      phenotype in India.

PMID- 27896143
TI  - New avenues for reducing intensive care needs in patients with chronic spinal
      cord injury.
AB  - Relatively soon after their accident, patients suffering a spinal cord injury
      (SCI) begin generally experiencing the development of significant, often life
      threatening secondary complications. Many of which are associated with chronic
      physical inactivity-related immune function problems and increasing
      susceptibility to infection that repeatedly requires intensive care treatment.
      Therapies capable of repairing the spinal cord or restoring ambulation would
      normally prevent many of these problems but, as of now, there is no cure for SCI.
      Thus, management strategies and antibiotics remain the standard of care although
      antimicrobial resistance constitutes a significant challenge for patients with
      chronic SCI facing recurrent infections of the urinary tract and respiratory
      systems. Identifying alternative therapies capable of safe and potent actions
      upon these serious health concerns should therefore be considered a priority.
      This editorial presents some of the novel approaches currently in development for
      the prevention of specific infections after SCI. Among them, brain-permeable
      small molecule therapeutics acting centrally on spinal cord circuits that can
      augment respiratory capabilities or bladder functions. If eventually approved by
      regulatory authorities, some of these new avenues may potentially become
      clinically-relevant therapies capable of indirectly preventing the occurrence
      and/or severity of these life-threatening complications in people with paraplegic
      or tetraplegic injuries.

PMID- 27896140
TI  - Multi-template polymerase chain reaction.
AB  - PCR is a formidable and potent technology that serves as an indispensable tool in
      a wide range of biological disciplines. However, due to the ease of use and often
      lack of rigorous standards many PCR applications can lead to highly variable,
      inaccurate, and ultimately meaningless results. Thus, rigorous method validation
      must precede its broad adoption to any new application. Multi-template samples
      possess particular features, which make their PCR analysis prone to artifacts and
      biases: multiple homologous templates present in copy numbers that vary within
      several orders of magnitude. Such conditions are a breeding ground for chimeras
      and heteroduplexes. Differences in template amplification efficiencies and
      template competition for reaction compounds undermine correct preservation of the
      original template ratio. In addition, the presence of inhibitors aggravates all
      of the above-mentioned problems. Inhibitors might also have ambivalent effects on
      the different templates within the same sample. Yet, no standard approaches exist
      for monitoring inhibitory effects in multitemplate PCR, which is crucial for
      establishing compatibility between samples.

PMID- 27896142
TI  - The reproducibility of biomedical research: Sleepers awake!
AB  - There is increasing concern about the reliability of biomedical research, with
      recent articles suggesting that up to 85% of research funding is wasted. This
      article argues that an important reason for this is the inappropriate use of
      molecular techniques, particularly in the field of RNA biomarkers, coupled with a
      tendency to exaggerate the importance of research findings.

PMID- 27896144
TI  - Clinical decision support for drug related events: Moving towards better
      prevention.
AB  - Clinical decision support (CDS) systems with automated alerts integrated into
      electronic medical records demonstrate efficacy for detecting medication errors
      (ME) and adverse drug events (ADEs). Critically ill patients are at increased
      risk for ME, ADEs and serious negative outcomes related to these events.
      Capitalizing on CDS to detect ME and prevent adverse drug related events has the
      potential to improve patient outcomes. The key to an effective medication safety
      surveillance system incorporating CDS is advancing the signals for alerts by
      using trajectory analyses to predict clinical events, instead of waiting for
      these events to occur. Additionally, incorporating cutting-edge biomarkers into
      alert knowledge in an effort to identify the need to adjust medication therapy
      portending harm will advance the current state of CDS. CDS can be taken a step
      further to identify drug related physiological events, which are less commonly
      included in surveillance systems. Predictive models for adverse events that
      combine patient factors with laboratory values and biomarkers are being
      established and these models can be the foundation for individualized CDS alerts
      to prevent impending ADEs.

PMID- 27896145
TI  - Interprofessional, multiple step simulation course improves pediatric resident
      and nursing staff management of pediatric patients with diabetic ketoacidosis.
AB  - AIM: To investigate the use of a multidisciplinary, longitudinal simulation to
      educate pediatric residents and nurses on management of pediatric diabetic
      ketoacidosis. METHODS: A multidisciplinary, multiple step simulation course was
      developed by faculty and staff using a modified Delphi method from the Pediatric
      Simulation Center and pediatric endocrinology department. Effectiveness of the
      simulation for the residents was measured with a pre- and post-test and a
      reference group not exposed to simulation. A follow up post-test was completed 3
      6 mo after the simulation. Nurses completed a survey regarding the education
      activity. RESULTS: Pediatric and medicine-pediatric residents (n = 20) and
      pediatric nurses (n = 25) completed the simulation course. Graduating residents
      (n = 16) were used as reference group. Pretest results were similar in the
      control and intervention group (74% +/- 10% vs 76% +/- 15%, P = 0.658). After
      completing the intervention, participants improved in the immediate post-test in
      comparison to themselves and the control group (84% +/- 12% post study; P <
      0.05). The 3-6 mo follow up post-test results demonstrated knowledge decay when
      compared to their immediate post-test results (78% +/- 14%, P = 0.761). Residents
      and nurses felt the interdisciplinary and longitudinal nature of the simulation
      helped with learning. CONCLUSION: Results suggest a multidisciplinary,
      longitudinal simulation improves immediate post-intervention knowledge but
      important knowledge decay occurs, future studies are needed to determine ways to
      decrease this decay.

PMID- 27896146
TI  - Determination of functional prognosis in hospitalized patients following an
      intensive care admission.
AB  - AIM: To investigate the factors associated with the functional progress of
      hospitalized patients following an intensive care admission. METHODS:
      Retrospective study including data from a cohort of 198 hospitalized patients
      following an intensive care admission and not requiring mechanical ventilation in
      a single tertiary referral hospital. A generalized linear model was used to
      identify the main effects of clinical and demographic variables on the outcomes
      of functionality (KATZ Index of Independence in Activities of Daily Living) and
      muscle strength (MRC Scale). The covariates identified as independent predictors
      were analysed using the receiver operating characteristic curves. The analysis
      differentiated the periods in the intensive care unit (ICU), in the Ward (WARD)
      and the total time of hospital stay (TOT). RESULTS: Considering the functional
      outcome (DeltaKATZ), the variables that significantly contributed to the model (P
      < 0.05) were the KATZ and MRC on admission, age, sepsis (no), and total length of
      stay (TLS). Regarding the muscle strength outcome model (DeltaMRC), the
      predictors were MRC on admission, Simplified Acute Physiology Score III, previous
      stroke, TLS, and sex (female). The variable age (AUC = 0.664) discriminated the
      DeltaKATZICU. The variables age (AUC = 0.712), KATZ in ICU (AUC = 0.590) and on
      ward admission (AUC = 0.746), and MRC on ward admission (AUC = 0.721) were
      discriminative for DeltaKATZWARD. For DeltaKATZTOT the variables KATZ on ICU
      admission (AUC = 0.621) and TLS (AUC = 0.617) were discriminative. For
      DeltaMRCICU the variables SAPSIII (AUC = 0.661) and MRC on ICU admission (AUC =
      0.653) were discriminative. MRC on ICU (AUC = 0.681) and ward admission (AUC =
      0.553) were discriminative for DeltaMRCWARD. TLS (AUC = 0.649) and MRC on ward
      admission (AUC = 0.696) discriminative for the DeltaMRCTOT. CONCLUSION: Specific
      functional, clinical and demographical variables at ICU admission are associated
      with the functional prognosis during the hospitalization period.

PMID- 27896147
TI  - Early debridement and delayed primary vascularized cover in forearm electrical
      burns: A prospective study.
AB  - AIM: To look into the management options of early debridement of the wound,
      followed by vascularized cover to bring in fresh blood supply to remaining tissue
      in electrical burns. METHODS: A total of 16 consecutive patients sustaining full
      thickness forearm burns over a period of one year were included in the study
      group. Debridement was undertaken within 48 h in 13 patients. Three patients were
      taken for debridement after 48 h. Debridement was repeated within 2-4 d after
      daily wound assessment and need for further debridement. RESULTS: On an average
      two debridements (range 1-4) was required in our patients for the wound to be
      ready for definitive cover. Interval between each debridement ranged from 2-18 d.
      Fourteen patients were provided vascularized cover after final debridement (6
      free flaps, 8 pedicled flaps). Functional assessment of gross hand function done
      at 6 wk, 2 mo, 3 mo and 6 mo follow-up. CONCLUSION: High-tension electrical burns
      lead to significant morbidity. These injuries are best managed by early
      decompression followed by multiple serial debridements. The ideal timing of free
      flap coverage needs further investigation.

PMID- 27896149
TI  - Congenital Neonatal Intestinal Obstruction.

PMID- 27896148
TI  - Plasma-Lyte 148: A clinical review.
AB  - AIM: To outline the physiochemical properties and specific clinical uses of
      Plasma-Lyte 148 as choice of solution for fluid intervention in critical illness,
      surgery and perioperative medicine. METHODS: We performed an electronic
      literature search from Medline and PubMed (via Ovid), anesthesia and pharmacology
      textbooks, and online sources including studies that compared Plasma-Lyte 148 to
      other crystalloid solutions. The following keywords were used: "surgery",
      "anaesthesia", "anesthesia", "anesthesiology", "anaesthesiology", "fluids",
      "fluid therapy", "crystalloid", "saline", "plasma-Lyte", "plasmalyte",
      "hartmann's", "ringers" "acetate", "gluconate", "malate", "lactate". All relevant
      articles were accessed in full. We summarized the data and reported the data in
      tables and text. RESULTS: We retrieved 104 articles relevant to the choice of
      Plasma-Lyte 148 for fluid intervention in critical illness, surgery and
      perioperative medicine. We analyzed the data and reported the results in tables
      and text. CONCLUSION: Plasma-Lyte 148 is an isotonic, buffered intravenous
      crystalloid solution with a physiochemical composition that closely reflects
      human plasma. Emerging data supports the use of buffered crystalloid solutions in
      preference to saline in improving physicochemical outcomes. Further large
      randomized controlled trials assessing the comparative effectiveness of Plasma
      Lyte 148 and other crystalloid solutions in measuring clinically important
      outcomes such as morbidity and mortality are needed.

PMID- 27896150
TI  - Early Reoperations after Primary Repair of Jejunoileal Atresia in Newborns.
AB  - Aim: To review nine-year experience in managing jejuno-ileal atresia (JIA) by
      primary resection and anastomosis and identify factors associated with
      reoperations. Methods: From April 2006 to May 2015, all consecutive neonates who
      underwent bowel resection and primary anastomosis for JIA were analyzed
      retrospectively. Patients with temporary enterostomy were excluded. Patient
      demographics, types of atresia, surgical techniques, need for reoperations, and
      long-term outcomes were investigated. Results: A total of forty-three neonates
      were included, in which nineteen (44.2%) of them were preterm and fourteen
      (32.6%) were of low birth weight. Thirteen patients (30.2%) had jejunal atresia
      whereas thirty patients (69.8%) had ileal atresia. Volvulus, intussusception and
      meconium peritonitis were noted in 12, 8, and13 patients, respectively. Eight
      patients (18.6%) had short bowel syndrome after operation. Ten patients (23.3%)
      required reoperations from 18 days to 4 months after the initial surgery due to
      anastomotic stricture (n=1), adhesive intestinal obstruction (n=1), small bowel
      perforation (n=2) and functional obstruction (n=6). Prematurity and low birth
      weight were associated with functional obstruction leading to reoperation (p=0.04
      and 0.01 respectively). The overall long-term survival was 97.7%. All surviving
      patients achieved enteral autonomy and catch-up growth at a median follow-up of
      4.7 years. Conclusion: Long-term survival of JIA after primary resection and
      anastomosis are excellent. However, patients have substantial risk of early
      reoperations to tackle intraabdominal complications.

PMID- 27896151
TI  - Alimentary Tract Atresias associated with Anorectal Malformations: 10 Years'
      Experience.
AB  - Anorectal malformation (ARM) is one of the most common congenital anomaly that
      requires emergency surgery in the neonatal period. ARMs are frequently associated
      with other life threatening congenital anomalies. Commonly associated anomalies
      are genito-urinary, cardiovascular, gastro-intestinal, skeletal and spinal.
      Alimentary tract anomalies are frequently masked by the intestinal obstruction
      produced by the anorectal atresia. This retrospective study was carried out to
      find out the incidence of associated alimentary tract atresias with ARM. In our
      series, out of 785 cases of high ARM, 14 cases had associated esophageal atresia
      (1.8%), followed by 7 cases of duodenal atresia (0.89%), and followed by pyloric
      atresia, jejuno-ileal atresia and colonic atresia.

PMID- 27896152
TI  - A Retrospective Cohort Study of Total Colonic Aganglionosis: Is the Appendix a
      Reliable Diagnostic Tool?
AB  - BACKGROUND: Hirschsprung's disease (HD) is characterized by a lack of ganglion
      cells in the myenteric and submucosal plexus, associated with increased numbers
      of acetyl cholinesterase (AChE) positive nerve fibres. In approximately 10% of
      patients with HD the entire colon will be affected; a condition known as Total
      Colonic Aganglionosis (TCA). Aganglionosis of the appendix has long been
      considered to be an important finding in a patient in whom TCA is suspected, but
      its reliability for diagnosis has seldom been discussed. The aim of our study was
      to assess the reliability of the appendix as a histological specimen for the
      diagnosis of TCA, and to evaluate the long-term outcome of TCA. METHODS: A
      retrospective cohort study was performed of all pathological specimens of
      patients with confirmed HD in our institution between March 2006 and April 2016.
      RESULTS: Out of a total of 91 patients identified, 15 patients also had
      histopathological analysis of the appendix. Nine of these cases were confirmed as
      having TCA. The remaining 6 patients had HD involving the rest of the bowel up to
      the ascending colon, with normal ganglion present in the caecum. The appendix was
      removed in all the 15 cases. All 9 patients with confirmed TCA had aganglionosis
      of the appendix as well. The remaining 6 cases of short and long segment HD not
      involving the caecum, demonstrated normal ganglion cells within the appendix.
      CONCLUSION: Aganglionosis of the appendix is a reliable tool in the diagnosis of
      TCA. The authors recommend that at the time of levelling biopsies, if
      aganglionosis extends to the mid-transverse colon, an ileostomy be performed and
      appendix sent for definitive confirmation of TCA. However, at the time of
      definitive surgery, a frozen section of pull-through segment of bowel is
      recommended to confirm the presence of ganglion cells.

PMID- 27896153
TI  - A Minor Innovation in Constructing a Small Bowel Stoma in Neonates with Small
      Bowel Atresia to Reduce the Morbidity.
AB  - BACKGROUND: Intestinal atresia has still significant morbidity in developing
      countries. Stomas are now not recommended in every case of intestinal atresia;
      primary anastomosis is the goal of surgery after resection of dilated adynamic
      gut. A new type of stoma formation along with primary anastomosis is being
      presented here. MATERIALS AND METHODS: This report is based on our experience of
      many cases with this technique in last 12 years but all the details and long
      follow-up of each case is not available. However the method of surgical
      procedure, progress, complications, and advantages encountered have been
      highlighted. RESULTS: Presently we have data of 7 patients; others are lost to
      follow up. Three had died with other associated problems, namely one with
      multiple atresias, two with septic shock and prematurity. Two stomas did not
      require formal closure because stoma shriveled and disappeared. Two other stomas
      had grown very long like a diverticulum when these were closed after 5 and 8
      months. CONCLUSION: This technique is another attempt to decrease morbidity of
      patients of intestinal atresia especially in those cases where short bowel
      syndrome is feared after resection of proximal dilated gut.

PMID- 27896154
TI  - Use of T-Tube Enterostomy in Neonatal Gastro-intestinal Surgery.
AB  - Aim: To evaluate the results of the use of the T-tube ileostomy in neonatal
      intestinal surgery cases. Materials and Methods: A retrospective review of sixty
      two neonates underwent intestinal obstruction surgery by using T-tube ileostomy
      was conducted between January 1990 and January 2013.The pathologies of the
      intestinal obstruction were; thirty four of jejunoileal atresia cases, thirteen
      case meconium ileus, eight cases perforated necrotizing enterocolitis (NEC),
      three cases meconium peritonitis, three cases with bowel resection due to
      intestinal volvulus, and one case of gastroschisis. Results: Mean duration of T
      tube placement was 13 days (range9-20days) and the sites of T-tube insertion
      closed spontaneously in 2 days (range 1-4 days). The mean duration for starting
      oral intake postoperatively in these patients was 9 days (6-16 days). All
      patients well tolerated the procedure and there were no serious complications
      related to the T-tube insertion. However, four patients died due to other reasons
      like sepsis, respiratory failure and prematurity. Conclusion: T-tube enterostomy
      is an effective and safe technique for treatment of selected cases of neonatal
      intestinal surgery. It showed less morbidity and mortality rates than the
      conventional stoma. Therefore, it is considered a helpful approach in cases where
      there is danger of hypoperistaltic dilated bowel proximal to the anastomosis.

PMID- 27896155
TI  - Colonic Atresia: Association with Other Anomalies.
AB  - BACKGROUND: Colonic atresia (CA) is a rare form of congenital intestinal atresia.
      Although CA may be isolated, it is more commonly reported in literature in
      association with other congenital anomalies. MATERIALS AND METHODS: This study is
      a review of prospectively collected data of all the patients with colonic atresia
      presented to our center (Ain Shams University) during 2008 to 2016. RESULTS:
      Twelve patients were enrolled in this study. The atresia was of type I in one
      case, type II in four cases, type IIIa in six cases, type IV in one case. These
      cases accounted for 4.9 % of intestinal atresias managed in our center during the
      same period. Five cases were isolated CA, while the other seven cases had
      associated abdominal congenital anomalies (exomphalos, Hirschsprung's disease,
      imperforate anus, closing gastroschisis, colonic duplication, and multiple small
      bowel atresia in two cases). The management in ten cases was by staged procedure
      with creation of a temporary stoma initially, while primary anastomosis was
      established in two cases. We had two cases with delayed presentations, one missed
      diagnosis, and three mortalities in this series. CONCLUSIONS: The low incidence
      of CA may result in delay in the diagnosis and management. Hirschsprung's disease
      should be excluded in every case of colonic atresia. Early diagnosis and proper
      surgical management is essential for good prognosis.

PMID- 27896156
TI  - Modified Gut Anastomotic Technique in Type III and Type IV Jejunoileal Atresias.
AB  - BACKGROUND: Type III and IV jejunoileal atresias are associated with loss of
      significant length of the gut and can lead to short gut syndrome if further
      resection of proximal dilated gut is done. We modified the anastomotic technique
      so that proximal dilated segment of the gut is not resected as to prevent short
      gut syndrome. MATERIAL AND METHODS: Medical Record of patients of Type III and IV
      jejuno-ileal atresias managed with modified anastomotic technique in our center
      during 5-years was reviewed. RESULTS: Fifteen patients were managed with our
      modified technique. There were no anastomotic leak observed and there was 6%
      mortality seen in our modified technique. CONCLUSION: We found less mortality and
      morbidity in our technique compared to recommended techniques described in
      literature.

PMID- 27896158
TI  - Congenital Duodenal Obstruction in Neonates: Over 13 Years' Experience from a
      Single Centre.
AB  - AIM: To study the prevalence of associated anomalies with neonatal duodenal
      obstruction and factors impacting short-term survival. MATERIAL AND METHODS:
      Records of 31 neonates with neonatal duodenal obstruction could be retrieved and
      analyzed for a 13.5-year-period (October 2003-May 2016). M:F ratio was 1.58:1.
      The mean birth weight was 2.15 kg; 12 patients were preterm. Etiologies included
      duodenal atresia (n=23), duodenal web (n=8) and malrotation of gut (n= 6).
      RESULTS: Associated anomalies were seen in 19/31: Down's syndrome (n=6),
      anorectal malformation (ARM) (n=5), annular pancreas (n=5), cardiac anomalies
      (n=4), esophageal atresia with trachea-esophageal fistula (EA with TEF) (n=3).
      Mortality in the series was 22.5%; 5 deaths and 2 patients left against medical
      advice in moribund state (hidden mortality). Mortality in associated anomalies
      group was 5/19; and 2/12 in the no anomalies group, though this difference was
      not statistically significant (p=0.676). Similarly, low birth weight (LBW) did
      not have impact on survival (p=0.639) but preterm status had highly significant p
      value (<0.001). CONCLUSION: Duodenal atresia was the commonest cause of neonatal
      duodenal obstruction. Associated anomalies were noted in 61% patients, Down's
      syndrome being the most frequent. These anomalies did not have any significant
      impact on the survival, nor did LBW. Preterm status had significant impact on
      prognosis.

PMID- 27896157
TI  - Congenital Neonatal Intestinal Obstruction: Retrospective Analysis at Tertiary
      Care Hospital.
AB  - BACKGROUND: The purpose of this study is to analyze the etiology, clinical
      presentation and outcome of neonatal intestinal obstruction at our institute.
      MATERIALS AND METHODS: The medical record of all the patients, presented with
      intestinal obstruction in neonatal period during 2014 and 2015 was reviewed
      retrospectively for etiology, clinical features, investigations, management, and
      outcome. RESULTS: Out of total 53 cases of neonatal intestinal obstruction, 27
      were of intestinal atresia (9 cases (17%) were of duodenal atresia, 7 (13%) were
      of jejunal atresia and 8 (13%) were ileal atresias and 3 cases were found with
      colonic atresia); 7 were malrotation, 17 were Hirschsprung's disease (HD). All
      the patients were investigated with abdominal radiography and sonography. All
      patients were managed surgically. Overall mortality was 10/53 (18.8%). Out of 27
      cases of atresia, 9 patients died (33% mortality). Septicemia was the cause of
      death in 7 patients (58.3%). Anastomotic leak was present in one mortality case.
      CONCLUSION: The most common cause of neonatal intestinal obstruction is atresia.
      Duodenal atresia was the most common atresia in our study followed by ileal
      atresia. Postoperative complications like septicemia led to most of deaths in our
      series. Septicemia, wound infection, hypothermia, prematurity need special
      attention for survival of neonates.

PMID- 27896159
TI  - Intestinal Atresia: Experience at a Busy Center of North-West India.
AB  - Objective: To evaluate the presentation, management, complications and outcome of
      intestinal atresia (IA) managed at our center over a period of 1 year. Materials
      and methods: Records of patients of IA admitted in our center from January 2015
      to December 2015 were retrospectively analyzed. Demographic data, antenatal
      history, presenting complaints, location (duodenal, jejunoileal, colonic) of
      atresia, surgery performed and peri-operative complications were noted. Results:
      Total 78 cases of IA were included in the analyses. Mean age and weight at the
      time of presentation was 5.8 days (range 0-50), and 1.9 kg (range 1.1-3.2),
      respectively. IA included duodenal atresia [DA (32)], jejuno-ileal atresia [JIA
      (40)], colonic atresia [CA (3)] and atresia at multiple-location (sites) in 3
      cases. Ninety percent of patients underwent surgery within 5 to 20 hours of
      admission. All cases of DA except one underwent Kimura's diamond shaped duodeno
      duodenostomy. One case with perforated duodenal web underwent duodenotomy with
      excision of web. Seven patients with JIA and CA required primary stoma, while
      rest were managed by excision of dilated proximal segment and primary
      anastomosis. Complications included anastomotic leak in 5, proximal perforation
      in 2, functional obstruction in 7, aspiration pneumonitis in 3, and wound
      infection in 6 patients. Mean hospital stay for survivors was 11 days. Overall
      survival was 63%. Conclusion: Late presentation, overcrowding in intensive care
      unit, septicemia, functional obstruction and anastomotic leak are the causes of
      poor outcome in our series. Early diagnosis, some modification in surgical
      technique, use of total parenteral nutrition and adequate investigations for
      other congenital anomalies may improve the outcome.

PMID- 27896160
TI  - Neonatal Intestinal Obstruction: When to Suspect Duplication Cyst of Bowel as the
      Cause.
AB  - BACKGROUND: Duplication cyst is a rare cause of neonatal intestinal obstruction.
      Their most common location is the small intestine. The clinical presentation is
      extremely variable depending upon its size, location and type and the age of the
      patient and are mainly encountered during infancy or early childhood. The
      diagnosis is very difficult in neonates. This study was undertaken to study their
      presentation, diagnostic modality of choice and further management in neonatal
      age group. MATERIALS AND METHODS: This was a retrospective study performed at the
      Department of Paediatric Surgery, J .N Medical College Hospital, AMU Aligarh from
      July 2008 to June 2014. The data was analyzed with respect to demographic profile
      of the neonates, their initial clinical presentation, radiological features and
      subsequent event leading to intervention, operative features and outcome.
      RESULTS: There were a total of seven neonates between ages of 3 days and 21 days
      who were diagnosed as cases of intestinal obstruction due to duplication cyst.
      The majority of the patients were having ileal duplication cyst (n=4).
      Ultrasonography played important role in majority of the cases for diagnosis.
      There was one patient in which the diagnosis was confused with ileal atresia. All
      the patients underwent excision with restoration of bowel continuity. CONCLUSION:
      The diagnosis of intestinal obstruction in neonate due to duplication cyst is
      difficult. It has varied presentation and preoperative diagnosis at times may be
      challenging. Surgery is the mainstay of the treatment.

PMID- 27896161
TI  - Distinct Presentations of Hernia of Umbilical Cord.
AB  - Hernia of umbilical cord is a well-known entity which presents with herniation of
      small bowel into the proximal part of umbilical cord. It has very good prognosis
      after surgical repair. Occasionally, it can have distinct presentations and
      varied malformations at the umbilicus which have bearing on the course of
      treatment and final outcome. Herein, we describe various presentations and
      malformations associated with hernia of umbilical cord. Embryological
      extrapolation is attempted for the malformations at umbilicus.

PMID- 27896162
TI  - Preduodenal Portal Vein Associated with Duodenal Obstruction of other Etiology: A
      Case Series.
AB  - DuodenalPreduodenal portal vein is a rare and interesting entity which often
      causes duodenal obstruction. It is also associated with other congenital
      anomalies. We report here three cases of preduodenal portal vein associated with
      other anomalies causing duodenal obstruction not related to direct compression by
      portal vein itself.

PMID- 27896163
TI  - Varied Presentation of Congenital Segmental Dilatation of the Intestine in
      Neonates: Report of Three Cases.
AB  - Congenital segmental dilatation (CSD) of the intestine is a rare developmental
      anomaly characterized by sharply demarcated dilatation of a gastrointestinal
      segment and may present with intestinal obstruction. We report three cases of CSD
      of the intestine in neonates with varied presentation. First patient was mistaken
      as pneumoperitoneum on abdominal radiograph, which led to initial abdominal drain
      placement. The 2nd patient was a case of anorectal malformation associated with
      congenital pouch colon (CPC) and CSD of ileum; and the third case presented as
      neonatal intestinal obstruction and found to have CSD of ileum. All the patients
      were successfully managed in our department.

PMID- 27896164
TI  - More Distally Located Duodenal Webs: A Case Series.
AB  - Duodenal atresia is a frequent cause of intestinal obstruction in the newborn.
      Obstruction due to duodenal web is infrequent, but its location other than second
      part of duodenum is rare with only a few cases reported in the literature. We are
      reporting three patients where we found duodenal webs at unusual locations. In
      one neonate the web was located at third part of duodenum and in other two
      patients the web was present at duodeno-jejunal junction (DJ).

PMID- 27896165
TI  - Jejunal Windsock Deformity: A Rare Cause of Incomplete Neonatal Intestinal
      Obstruction.
AB  - Incomplete intestinal obstruction due to windsock web of the jejunum is
      uncommonly noticed in neonates. We present a male neonate, prenatally suspected
      case of proximal bowel obstruction, who was found to have features of incomplete
      intestinal obstruction due to windsock deformity in jejunum. The difficulty in
      the diagnosis and management is discussed along with relevant literature review.

PMID- 27896166
TI  - Congenital Middle Mesocolic Hernia: A Rare Cause of Neonatal Intestinal
      Obstruction.
AB  - Congenital mesocolic hernia is an extremely rare, but serious cause of intestinal
      obstruction in children. Given the rarity of this condition, delays in diagnosis
      and management can have catastrophic consequences. Congenital mesocolic hernias
      are usually caused by an abnormal rotation of primitive mid-gut and are divided
      into left and right congenital mesocolic hernias. We report and discuss the
      clinical and radiological features and management of a neonate with an extremely
      rare variant, congenital middle mesocolic hernia along with a literature review
      of this rare condition.

PMID- 27896167
TI  - Imperforate Anus with Jejunal Atresia Complicated by Intestinal Volvulus: A Case
      Report.
AB  - Anorectal malformations (ARMs) commonly co-occur with other congenital anomalies,
      particularly VACTERL (vertebral, anorectal, cardiac, tracheal, esophageal, renal,
      limb, and duodenal) associations. However, this collection of associations is not
      comprehensive, and other concurrent anomalies may exist that can be missed during
      the standard work-up of patients with ARMs. We present a rare case of a neonate
      with a low ARM with concurrent jejuno-ileal atresia that was diagnosed after the
      correction of the ARM when the patient developed segmental volvulus. This case
      illustrates the importance of having a high index of suspicion when deviation
      from a classic presentation occurs.

PMID- 27896168
TI  - Duodenal Atresia Associated with Apple Peel Atresia and Situs Inversus Abdominus:
      A Case Report.
AB  - Duodenal atresia is rarely associated with situs inversus abdominus. We report a
      case of duodenal atresia associated with small bowel atresia of apple peel type
      and situs inversus abdominus.

PMID- 27896169
TI  - Rare Association of Extended Total Colonic Aganglionosis and Intestinal
      Malrotation.
AB  - Total colonic aganglionosis occurring together with malrotation is a rare
      occurrence and may pose diagnostic and management dilemmas for the paediatric
      surgeon. We report a case of a neonate that presented with extended total colonic
      aganglionosis and malrotation, along with a spectrum of central nervous system
      and renal abnormalities. The clinical and radiological features and potential
      diagnostic and management pitfalls are discussed along with a literature review
      of this exceptionally infrequent association.

PMID- 27896170
TI  - Postoperative Gastric Perforation in a Newborn with Duodenal Atresia.
AB  - Gastric perforation (GP) in neonates is a rare entity with high mortality.
      Although the etiology is not completely understood, it mostly occurs in premature
      neonates on assisted ventilation. Combination of duodenal atresia and gastric
      perforation is very rare. We present a case duodenal atresia who developed
      gastric perforation after operetion for duodenal atresia. Analysis of the patient
      medical record and histology report did not reveal the etiology of the
      perforation.

PMID- 27896171
TI  - Isolated Jejunal Duplication Cyst Associated with Intestinal Malrotation in a
      Newborn.

PMID- 27896172
TI  - Congenital Hernia of the Umbilical Cord associated with type IIIa Ileal Atresia.

PMID- 27896173
TI  - Closed Gastroschisis with Vanished Small Bowel and Jejunal Atresia.

PMID- 27896174
TI  - Congenital Pouch Colon with Rectal Atresia: A Rare Association.

PMID- 27896175
TI  - Congenital Cecal Duplication Cyst Mimicking as Intramural Mass.

PMID- 27896176
TI  - How to Add a Journal to the International Databases, Science Citation Index
      Expanded and MEDLINE.

PMID- 27896177
TI  - Anti-Vascular Endothelial Growth Factor (Bevacizumab) Therapy Reduces
      Hypertrophic Scar Formation in a Rabbit Ear Wounding Model.
AB  - BACKGROUND: Hypertrophic scarring is a pathological condition that occurs after
      trauma or surgery. Angiogenesis occurs more often with hypertrophic scarring than
      with normotrophic scarring. The regulation of angiogenesis is one of the key
      factors in hypertrophic scar management. Vascular endothelial growth factor
      (VEGF) is an essential factor in the angiogenetic response. This study
      investigated whether decreasing the level of VEGF is effective for treating
      hypertrophic scarring. METHODS: Ten 8-week-old female New Zealand white rabbits
      were included. Four defects were created on each ear by using a 6-mm punch.
      Bevacizumab (Avastin, Roche Pharma, Basel, Switzerland) was administered in one
      ear and normal saline was administered in the other ear. Treatment was
      administered starting on day 2, every 2 days, until day 14. The levels of VEGF
      were measured using enzyme-linked immunosorbent assay on day 10 and histologic
      results were analyzed on day 40. RESULTS: Bevacizumab induced-defects showed less
      hypertrophic scarring when compared with the control group as measured by the
      scar elevation index (SEI) and loose collagen arrangement. The SEI in the
      experimental group was 1.89+/-0.13, compared to 1.99+/-0.13 in the control group
      (n=30, P=0.005). Additionally, the VEGF level was lower (38.72+/-11.03 pg vs.
      82.50+/-21.64 pg, n=10, P=0.001) and fewer vessels existed (8.58+/-0.76 vs. 7.2+/
      1.20, n=10, P=0.007). CONCLUSIONS: Preventing excessive angiogenesis is effective
      for preventing scar formation, especially with hypertrophic scarring. Although it
      is not an approach that is sufficient alone for the management of scarring, it
      may be one of several important strategies for scar treatment.

PMID- 27896178
TI  - Comparison of Saccharina japonica-Undaria pinnatifida Mixture and Minoxidil on
      Hair Growth Promoting Effect in Mice.
AB  - BACKGROUND: Algae have traditionally been used for promotion of hair growth. Use
      of hair regrowth drugs, such as minoxidil, is limited due to side effects. The
      aim of this study was to examine a mixture of Saccharina japonica and Undaria
      pinnatifida (L-U mixture) on hair growth and to compare the promoting effect of
      hair growth by a 3% minoxidil and a L-U mixture. METHODS: To evaluate the hair
      growth-promoting activity, saline, 50% ethanol, 3% minoxidil, and the L-U mixture
      were applied 2 times a day for a total of 14 days on the dorsal skin of C57BL/6
      mice after depilation. Analysis was determined by using a high-resolution hair
      analysis system, real-time polymerase chain reaction, and H&E staining. RESULTS:
      On day 14, the hair growth effect of the L-U mixture was the same as that of the
      3% minoxidil treatment. The L-U mixture significantly (P<0.05) stimulated hair
      growth-promoting genes, as vascular endothelial growth factor (VEGF) and insulin
      like growth factor -1. Increase of VEGF was observed in the L-U mixture group
      compared with minoxidil and the negative control. In contrast, the L-U mixture
      suppressed the expression of transforming growth factor-beta1, which is the hair
      loss-related gene. In histological examination in the L-U mixture and minoxidil
      groups, the induction of an anagen stage of hair follicles was faster than that
      of control groups. CONCLUSIONS: This study provides evidence that the L-U mixture
      can promote hair growth in mice, similar to the effect from minoxidil, and
      suggests that there is potential application for hair loss treatments.

PMID- 27896179
TI  - Clinical Factors Associated with the Non-Operative Airway Management of Patients
      with Robin Sequence.
AB  - BACKGROUND: The indications for surgical airway management in patients with Robin
      sequence (RS) and severe airway obstruction have not been well defined. While
      certain patients with RS clearly require surgical airway intervention and other
      patients just as clearly can be managed with conservative measures alone, a
      significant proportion of patients with RS present with a more confusing and
      ambiguous clinical course. The purpose of this study was to describe the clinical
      features and objective findings of patients with RS whose airways were
      successfully managed without surgical intervention. METHODS: The authors
      retrospectively reviewed the medical charts of infants with RS evaluated for
      potential surgical airway management between 1994 and 2014. Patients who were
      successfully managed without surgical intervention were included. Patient
      demographics, nutritional and respiratory status, laboratory values, and
      polysomnography (PSG) findings were recorded. RESULTS: Thirty-two infants met the
      inclusion criteria. The average hospital stay was 16.8 days (range, 5-70 days).
      Oxygen desaturation (<70% by pulse oximetry) occurred in the majority of patients
      and was managed with temporary oxygen supplementation by nasal cannula (59%) or
      endotracheal intubation (31%). Seventy-five percent of patients required a
      temporary nasogastric tube for nutritional support, and a gastrostomy tube placed
      was placed in 9%. All patients continued to gain weight following the
      implementation of these conservative measures. PSG data (n=26) demonstrated mild
      to moderate obstruction, a mean apneahypopnea index (AHI) of 19.2+/-5.3
      events/hour, and an oxygen saturation level <90% during only 4% of the total
      sleep time. CONCLUSIONS: Nonsurgical airway management was successful in patients
      who demonstrated consistent weight gain and mild to moderate obstruction on PSG,
      with a mean AHI of <20 events/hour.

PMID- 27896180
TI  - Correction of Congenital Auricular Deformities Using the Ear-Molding Technique.
AB  - BACKGROUND: Studies of the ear-molding technique have emphasized the importance
      of initiating molding early to achieve the best results. In the present study, we
      describe the immediate effects and long-term outcomes of this technique, focusing
      on children who were older than the ideal age of treatment initiation. METHODS:
      Patients who visited our institution from July 2014 to November 2015 were
      included. Medical charts were reviewed to collect data on demographics, the
      duration of treatment, the types of deformities, and the manner of recognition of
      the deformity and referral to our institution. Parents were surveyed to assess
      the degree of improvement, the level of procedural discomfort at the end of
      treatment, any changes in the shape of the molded auricle, and overall
      satisfaction 12 months after their last follow-up visits. RESULTS: A review of 28
      ears in 18 patients was conducted, including the following types of deformities:
      constricted ear (64.2%), Stahl ear (21.4%), prominent ear (7.1%), and cryptotia
      (7.1%). The average score for the degree of improvement, rated on a 5-point scale
      (1, very poor; 5, excellent), was 3.5 at the end of treatment, with a score of
      2.6 for procedural discomfort (1, very mild; 5, very severe). After 12 months,
      the shapes of all ears were well maintained. The average overall satisfaction
      score was 3.6 (1, very dissatisfied; 5, very satisfied). CONCLUSIONS: We had
      reasonable outcomes in older patients. After 1 year of follow-up, these outcomes
      were well maintained. Patients past the ideal age at presentation can still be
      candidates for the molding technique.

PMID- 27896181
TI  - The Correlation between the Orbital Volume Ratio and Enophthalmos in Unoperated
      Blowout Fractures.
AB  - BACKGROUND: Enophthalmos may not appear immediately after trauma due to
      periorbital swelling in a blowout fracture, and preoperative measurements of
      enophthalmos cannot be used as a reliable guideline. It is important to predict
      the eventual final extent of enophthalmos in order to determine whether to
      perform surgery, and there have been several attempts to predict the degree of
      late enophthalmos using preoperative orbital volume. The purpose of this study is
      to investigate the correlation between the orbital volume ratio (OVR) with final
      enophthalmos and the palpebral fissure, and to find the OVR that induced 2 mm of
      enophthalmos in unilateral unoperated blowout fractures. METHODS: We
      retrospectively reviewed the medical records of 38 patients and divided them into
      3 groups, determined by the fracture location. The relationships between the OVR
      and both the degree of enophthalmos and the palpebral fissure ratio (PFR) were
      assessed and, in particular, the OVR that induced 2 mm of enophthalmos was
      sought. RESULTS: Enophthalmos increased in proportion to the OVR, and there was a
      highly significant correlation between the increase in the OVR and the degree of
      enophthalmos (P<0.05). On the other hand, there was no correlation between OVR
      and PFR (P>0.05). The OVR that induced 2-mm enophthalmos was 112.18%.
      CONCLUSIONS: The final degree of enophthalmos can be estimated by the
      preoperative measurement of OVR. Preoperative measurements of OVR can be used as
      quantitative values to predict the final degree of enophthalmos in pure blowout
      fractures.

PMID- 27896182
TI  - The Effect of Sterile Acellular Dermal Matrix Use on Complication Rates in
      Implant-Based Immediate Breast Reconstructions.
AB  - BACKGROUND: The use of acellular dermal matrix (ADM) in implant-based immediate
      breast reconstruction has been increasing. The current ADMs available for breast
      reconstruction are offered as aseptic or sterile. No published studies have
      compared aseptic and sterile ADM in implant-based immediate breast
      reconstruction. The authors performed a retrospective study to evaluate the
      outcomes of aseptic versus sterile ADM in implant-based immediate breast
      reconstruction. METHODS: Implant-based immediate breast reconstructions with ADM
      conducted between April 2013 and January 2016 were included. The patients were
      divided into 2 groups: the aseptic ADM (AlloDerm) group and the sterile ADM
      (MegaDerm) group. Archived records were reviewed for demographic data and
      postoperative complication types and frequencies. The complications included were
      infection, flap necrosis, capsular contracture, seroma, hematoma, and
      explantation for any cause. RESULTS: Twenty patients were reconstructed with
      aseptic ADM, and 68 patients with sterile ADM. Rates of infection (15.0% vs.
      10.3%), flap necrosis (5.0% vs. 7.4%), capsular contracture (20.0% vs. 14.7%),
      seroma (10.0% vs. 14.7%), hematoma (0% vs. 1.5%), and explantation (10.0% vs.
      8.8%) were not significantly different in the 2 groups. CONCLUSIONS: Sterile ADM
      did not provide better results regarding infectious complications than aseptic
      ADM in implant-based immediate breast reconstruction.

PMID- 27896184
TI  - Discussion: The Trapezius Muscle Flap: A Viable Alternative for Posterior Scalp
      and Neck Reconstruction.

PMID- 27896183
TI  - The Trapezius Muscle Flap: A Viable Alternative for Posterior Scalp and Neck
      Reconstruction.
AB  - BACKGROUND: The trapezius muscle flap is not usually the first reconstructive
      option for skin and soft tissue defects in the posterior neck and scalp due to
      surgeons' unfamiliarity with the surgical anatomy and developments in free tissue
      transfer techniques. The goals of this study were to describe the clinical use of
      trapezius flaps in posterior neck and scalp reconstruction, and to investigate
      the vascular anatomy of trapezius flaps in Asians in order to obtain information
      facilitating the safe design and elevation of flaps in which most of the muscle
      is preserved. METHODS: A retrospective chart review was performed of 10 patients
      who underwent trapezius muscle flap for posterior neck and scalp defects. We also
      performed an anatomical study of 16 flaps harvested from 8 preserved Asian adult
      cadavers and evaluated the main landmarks relevant for trapezius muscle flap.
      RESULTS: In the anatomical study, the mean vertical height from the inferior
      angle of the scapula to the point at which the superficial cervical artery
      penetrated the trapezius was 4.31+/-2.14 cm. The mean vertical height of the
      trapezius muscle flap pivot point was 9.53+/-2.08 cm from the external occipital
      protuberance. Among the 10 flaps, partial necrosis on the overlaid skin graft
      occurred in 1 patient and postoperative seroma occurred in another patient.
      CONCLUSIONS: Vascular variations in the trapezius muscle flap are uncommon in
      Asians, but when present, such variations appear to have little impact on
      harvesting the flap or on its circulation. The trapezius muscle flap is a viable
      alternative for posterior neck and scalp reconstruction.

PMID- 27896185
TI  - The Relationship between the Size and the Invasion Depth of Tumors in Head and
      Neck Cutaneous Squamous Cell Carcinoma.
AB  - BACKGROUND: Cutaneous squamous cell carcinoma (SCC), which occurs in
      keratinocytes of the epidermis and is the second most common skin cancer, has a
      more invasive growth pattern and higher potential to metastasize than basal cell
      carcinoma. Total excision of the primary tumor is the treatment of choice. For
      clear excision of the tumor, invasion depth is one of the most important factors.
      This study was conducted to clarify the relationship between the size and the
      invasion depth of cutaneous SCC. METHODS: Twenty-six cases were collected for
      this prospective study. Frozen biopsies were examined after complete resection of
      the tumor, followed by histological confirmation by pathological examination. The
      major and minor axis lengths of the tumor, the invasion depth, and the level of
      invasion were measured. Recurrence or metastasis was recorded through regular
      follow-up. RESULTS: The Pearson correlation coefficient was used for statistical
      analysis. Significant results were observed for the relationship between the
      major and minor axis lengths and the invasion depth of the tumor (0.747, 0.773).
      No cases of recurrence or metastasis were observed. CONCLUSIONS: In head and neck
      cutaneous SCC, the invasion depth of the tumor is closely related to the major
      and minor axis lengths of the tumor. Therefore, the invasion depth of the tumor
      can be estimated by measuring the size of the tumor, and a standard vertical
      safety margin for head and neck cutaneous SCC can be established, which could be
      helpful in the development of a preoperative reconstruction plan.

PMID- 27896186
TI  - Use of a Temporary Shunt as a Salvage Technique for Distal Extremity Amputations
      Requiring Repair by Vessel Grafting during Critical Ischemia.
AB  - BACKGROUND: Although the use of temporary shunts in proximal extremity
      amputations has been reported, no study has described the use of temporary shunts
      in distal extremity amputations that require vein grafting. Moreover, the total
      volume of blood loss when temporary shunts are used has not been reported. The
      aim of this study was to investigate the applicability of a temporary shunt for
      distal extremity amputations requiring repair by vessel grafting with an ischemia
      time of >6 hours. This study also aimed to determine the total volume of blood
      loss when temporary shunts were used. METHODS: Patients who underwent distal
      major extremity replantation and/or revascularization with a vessel graft and who
      experienced ischemia for 6-8 hours between 2013 and 2014 were included in the
      study. A 6-Fr suction catheter was cut to 5 cm in length after the infusion of
      heparin, and secured with a 5-0 silk suture between the distal and the proximal
      ends of the artery. While bleeding continued, the bones were shortened and fixed.
      After the complete restoration of circulation, the arterial shunt created using
      the catheter was also repaired with a vein graft. RESULTS: Six patients were
      included in this study. The mean duration of ischemia was 7.25 hours. The mean
      duration of suction catheter use during limb revascularization was 7 minutes. The
      mean transfusion volume was 7.5 units. No losses of the extremity were observed.
      CONCLUSIONS: This procedure should be considered in distal extremity amputations
      requiring repair by vessel grafting during critical ischemia.

PMID- 27896187
TI  - Fascial Free Flap for Reconstruction of the Dorsolateral Hand and Digits: The
      Advantage of a Thin Contour.
AB  - BACKGROUND: Fascial free flaps have been widely used for reconstruction of the
      hand because they are thin. However, studies reporting objective data regarding
      the advantages of this approach are lacking. Thus, we report our experience with
      such flaps. METHODS: Forty-five cases of fascial free flaps between November 2006
      and March 2014 were reviewed. Nine cases involving reconstructed dorsal or
      lateral defects were included. Four anterolateral thigh fascial free flaps and 5
      lateral arm fascial free flaps were examined. Maximal flap contour was assessed
      by measuring reconstructed tissue thickness at the central area from the surface
      of the skin to below the bone in a vertical manner using ultrasonography and X
      ray data. Contralateral regions were examined in the same manner and a
      comparative analysis was performed. A questionnaire survey regarding aesthetic
      satisfaction was also administered. RESULTS: All reconstructed parts had a
      thicker contour than the contralateral side. The average relative percentage of
      reconstructed tissue thickness was found to be 152% using ultrasonography and
      143% using X-ray imaging. According to the aesthetic satisfaction survey, the
      average rate of satisfaction for patients was 62%, and satisfaction with the flap
      contour was 72%. CONCLUSIONS: Using a fascial free flap, the reconstructed tissue
      was approximately 1.5* as thick as the contour of the normal side, which led to
      positive responses regarding aesthetic satisfaction.

PMID- 27896188
TI  - Foot Syndactyly: A Clinical and Demographic Analysis.
AB  - BACKGROUND: Syndactyly of the foot is the second most common congenital foot
      anomaly. In East Asia, however, no large case study has been reported regarding
      the clinical features of isolated foot syndactyly. In this study, we report a
      review of 118 patients during the last 25 years. METHODS: We conducted a chart
      review of patients who underwent surgical correction for foot syndactyly between
      January 1990 and December 2014. Operations were performed with a dorsal
      triangular flap and a full-thickness skin graft. The demographics of included
      patients and their clinical features were evaluated. Surgical outcomes and
      complications were analyzed. RESULTS: Among 118 patients with 194 webs (155
      feet), 111 patients showed nonsyndromic cases and 7 patients showed syndromic
      cases. In 80 unilateral cases (72.1%), the second web was the most frequently
      involved (37.5%), followed by the fourth (30%), the first (15%), the third (15%),
      the first and second in combination (1.3%), and the second and third in
      combination (1.3%). Among 31 bilateral cases, 2 cases were asymmetric. Among the
      remaining 29 symmetric bilateral cases, the second web was the most frequently
      involved (45.2%), followed by the first (22.6%), and the fourth (6.5%). No
      specific postoperative complications were observed, except in the case of 1
      patient (0.51%) who required a secondary operation to correct web creep.
      CONCLUSIONS: This retrospective clinical study of 118 patients with both
      unilateral and bilateral foot syndactyly revealed that the second web was the
      most frequently involved. In addition, complete division and tension-free wound
      closure with a full-thickness skin graft of sufficient size showed good
      postoperative results.

PMID- 27896189
TI  - Simple Correction of Alar Retraction by Conchal Cartilage Extension Grafts.
AB  - BACKGROUND: Alar retraction is a challenging condition in rhinoplasty marked by
      exaggerated nostril exposure and awkwardness. Although various methods for
      correcting alar retraction have been introduced, none is without drawbacks.
      Herein, we report a simple procedure that is both effective and safe for
      correcting alar retraction using only conchal cartilage grafting. METHODS:
      Between August 2007 and August 2009, 18 patients underwent conchal cartilage
      extension grafting to correct alar retraction. Conchal cartilage extension grafts
      were fixed to the caudal margins of the lateral crura and covered with vestibular
      skin advancement flaps. Preoperative and postoperative photographs were reviewed
      and analyzed. Patient satisfaction was surveyed and categorized into 4 groups
      (very satisfied, satisfied, moderate, or unsatisfied). RESULTS: According to the
      survey, 8 patients were very satisfied, 9 were satisfied, and 1 considered the
      outcome moderate, resulting in satisfaction for most patients. The average
      distance from the alar rim to the long axis of the nostril was reduced by 1.4 mm
      (3.6 to 2.2 mm). There were no complications, except in 2 cases with palpable
      cartilage step-off that resolved without any aesthetic problems. CONCLUSIONS:
      Conchal cartilage alar extension graft is a simple, effective method of
      correcting alar retraction that can be combined with aesthetic rhinoplasty
      conveniently, utilizing conchal cartilage, which is the most similar cartilage to
      alar cartilage, and requiring a lesser volume of cartilage harvest compared to
      previously devised methods. However, the current procedure lacks efficacy for
      severe alar retraction and a longer follow-up period may be required to
      substantiate the enduring efficacy of the current procedure.

PMID- 27896190
TI  - The Use of Locally Applied Vibration to Minimize Pain during Fractional CO2 Laser
      Therapy in Living Liver-Donor Scar Management.
AB  - BACKGROUND: Fractional CO2 laser is an effective treatment for scars, but most
      patients complain about sharp burning pain, even after the application of
      lidocaine ointment. This study analyzed the impact of a vibrating device to
      nonpharmacologically reduce the acute pain of laser treatment, in accordance with
      the gate control theory of pain management. METHODS: This is a prospective study
      performed from May 2013 through March 2014. Fifty-three patients (mean age, 26.7
      years; range, 16-44 years) who had donated livers for liver transplantation were
      treated with a fractional CO2 laser (10,600 nm; model eCO2, Lutronic Corp) for
      their abdomen scars. Laser treatment was applied 4 months after surgery. A
      commercially available, locally applied vibrating device (model UM-30M, Unix
      Electronics Co. Ltd.) was used, in an on-and-off pattern, together with the CO2
      laser. A visual analogue scale (VAS; 0, no pain; 10, most severe pain) of pain
      sensation was assessed and statistically analyzed using a paired t-test. RESULTS:
      The average VAS score for pain with the vibrating device was 4.60 and the average
      VAS score without the vibrating device was 6.11. The average difference between
      scores was 1.51 (P=0.001). CONCLUSIONS: A locally applied vibrating device was
      demonstrated to be effective in reducing pain when treating with a fractional CO2
      laser. Vibration treatment could be helpful when treating scars with fractional
      CO2 laser in pain-sensitive patients, particularly children.

PMID- 27896191
TI  - Comparison of the Effectiveness of Ablative and Non-Ablative Fractional Laser
      Treatments for Early Stage Thyroidectomy Scars.
AB  - BACKGROUND: Open thyroidectomy is conventionally performed at the anterior side
      of neck, which is a body part with a comparatively great degree of open exposure;
      due to this, postoperative scarring may cause distress in patients. We aimed to
      compare the effects of ablative and nonablative fractional laser treatments on
      thyroidectomy scars. We examined medical records in a retrospective manner and
      analyzed scars based on their digital images by using the modified Manchester
      Scar Scale (mMSS). METHODS: Between February 2012 and May 2013, 55 patients with
      thyroidectomy scars were treated with ablative (34 patients) or nonablative (21
      patients) fractional laser. Each patient underwent 4 laser treatment sessions in
      3-4 week intervals, 1-2 months postoperatively. Scar improvement was assessed
      using patient images and the mMSS scale. RESULTS: The mean decrease in scar score
      was 3.91 and 3.47 in the ablative and nonablative groups, respectively; the
      reduction between 2 groups did not exhibit any significant difference (P=0.16).
      We used the scale once again to individually evaluate scar attributes. The
      nonablative group accounted for a considerably higher color score value (P=0.03);
      the ablative group accounted for a considerably higher contour score value
      (P<0.01). Patient satisfaction was high and no complications occurred.
      CONCLUSIONS: Both types of fractional laser treatments can be used successfully
      for thyroidectomy scar treatment with minimal complications; however, results
      indicate that higher effectiveness may be obtained from the use of ablative and
      nonablative lasers for hypertrophic scars and early erythematous scars,
      respectively. Therefore, the appropriate laser for scar treatment should be
      selected according to its specific characteristics.

PMID- 27896192
TI  - Acquired Palatal Fistula in Patients with Submucous and Incomplete Cleft Palate
      before Surgery.
AB  - It is uncommon for a palatal fistula to be detected in individuals who have not
      undergone surgery, and only sporadic cases have been reported. It is even more
      difficult to find cases of acquired palatal fistula in patients with submucous or
      incomplete cleft palate. Herein, we present 2 rare cases of this phenomenon. Case
      1 was a patient with submucous cleft palate who acquired a palatal fistula after
      suffering from oral candidiasis at the age of 5 months. Case 2 was a patient with
      incomplete cleft palate who spontaneously, without trauma or infection, presented
      with a palatal fistula at the age of 9 months.

PMID- 27896193
TI  - Multidisciplinary Approach to an Extended Pressure Sore at the Lumbosacral Area.
AB  - A pressure sore wound is often extensive or complicated by local infection
      involving adjacent soft tissue and bone. In this case, a regional flap after
      simple debridement is not adequate. Here, we present a case of an extensive
      pressure sore in the sacral area with deep tissue infection. A 43-year-old female
      patient with a complicated sore with deep tissue infection had a presacral
      abscess, an iliopsoas abscess, and an epidural abscess in the lumbar spine. After
      a multidisciplinary approach performed in stages, the infection had subsided and
      removal of the devitalized tissue was possible. The large soft tissue defect with
      significant depth was reconstructed with a free latissimus dorsi musculocutaneous
      flap, which was expected to act as a local barrier from vertical infection and
      provide tensionless skin coverage upon hip flexion. The extensive sacral sore was
      treated effectively without complication, and the deep tissue infection
      completely resolved. There was no evidence of donor site morbidity, and
      wheelchair ambulation was possible by a month after surgery.

PMID- 27896194
TI  - Osteomyelitis following Domestic Animal Bites to the Hand: Two Case Reports and
      Practical Guidelines.
AB  - Recently, the number of cases of animal bite wounds has increased significantly
      in concordance with an increase in the pet population around the world. The
      authors report two rare cases of osteomyelitis of the phalanx following cat and
      dog bites. On initial physical examination, signs of a severe infection were
      observed. Radiographs of both patients showed the presence of osteomyelitis, and
      in one of the patients, the diagnosis was confirmed with a bone biopsy. After use
      of empirical antibiotics, intravenous antibiotic therapy that matched the
      identified bacterium's sensitivity was initiated, and at the same time, secure
      dressing including debridement was performed to induce secondary healing. In
      addition, the patients were closely monitored with serial X-rays, and culture and
      blood test follow-up. One patient fully recovered without sequelae, but the other
      patient suffered a loss of distal interphalangeal joint motion. When dealing with
      bite wounds located on the hand, it is important to visit the hospital as soon as
      possible and receive the appropriate treatment early. Moreover, to prevent severe
      complications such as osteomyelitis, it is important to administer antibiotic
      therapy to which the cultured bacteria are sensitive, along with proper wound
      management and prophylactic antibiotic treatment.

PMID- 27896195
TI  - Microsurgical Training using Reusable Human Vessels from Discarded Tissues in
      Lymph Node Dissection.
AB  - The use of human vessels at the beginning of microsurgery training is highly
      recommended. But vessels with the appropriate length for training are not often
      obtained. Whether these vessels may be reused for training has not been reported.
      Accordingly, we harvested vessels from discarded tissues in lymph node dissection
      and demonstrated that vascular anastomosis training using the same human vessels
      several times is possible by placing the vessels in a freezer and defrosting them
      with hot water. Vascular walls can be stored for microsurgical training until
      about 4 years after harvest, as shown in the gross appearance and histologic
      findings of our preserved vessels. We recommend the technique presented here for
      the longterm reuse of human vessels for microsurgery training that closely
      resembles real procedures.

PMID- 27896196
TI  - Microdissected Prefabricated Flap: An Evolution in Flap Prefabrication.
AB  - When traditional flap techniques are not feasible, we apply flap prefabrication,
      which is more complicated and sophisticated but supplies large and thin flaps.
      There are some disadvantages to the technique that require improvement, such as
      venous congestion after flap transfer, which requires months for neoangiogenesis
      and necessitates a vascular carrier. Here, the author presents a new technique,
      called as 'microdissected prefabricated flap,' to successfully produce a safe,
      large, and thin flap. This technique is based on the microdissection of the
      perforators to the greatest extent possible, spreading them out into the
      subdermal level and using them as a carrier. The details and the application of
      this technique are presented and reported.

PMID- 27896197
TI  - A Refined Technique for Management of Nasal Flaring: The Quest for the Holy Grail
      of Alar Base Modification.
AB  - "A smile is happiness you'll find right under your nose"- Tom Wilson. This quote
      holds true just for patients, not for surgeons. The correction of the nose always
      poses a challenge to the cosmetic surgeon. Deformities of the external and
      internal nose may be congenital or acquired and may be secondary to soft tissue
      and/or osseo-cartilaginous abnormalities, leading to aesthetic and/or functional
      consequences. Alar flare poses a common problem, sometimes alone and sometimes in
      conjunction with other external deformities. Alar base reduction is generally
      considered when the interalar distance exceeds the intercanthal distance. It has
      been well documented that this simple additional procedure brings about a
      substantial enhancement in the nose. Various techniques have been described and
      used in the past, each having their benefits and drawbacks, with the modified
      Weir wedge excision, Aufricht nasal sill excision, and Bernstein V-Y advancement
      being the common ones. We hereby describe a technique that is simple yet
      effective in achieving the desired results and at the same time aims at
      preventing relapse to obtain satisfactory long term results.

PMID- 27896198
TI  - Bilateral Dermoid Cysts on the Lateral Ends of Eyebrows.

PMID- 27896199
TI  - Botulinum Toxin and Burn Induces Contracture.

PMID- 27896200
TI  - Full Thickness Burn on the Finger due to Pulse Oximetry during Magnetic Resonance
      Imaging in a Conscious Patient.

PMID- 27896201
TI  - Primary Necrotizing Fasciitis of the Breast in an Untreated Patient with
      Diabetes.

PMID- 27896202
TI  - A Band-Like Neck Scar Contracture after Bilateral Axillo-Breast Approach Robotic
      Thyroidectomy.

PMID- 27896203
TI  - Soft Tissue Reconstruction for Basaloid Squamous Cell Carcinoma on the Hemiface.

PMID- 27896204
TI  - A Pedunculated Giant Cutaneous Horn Variant Overlying Invasive Squamous Cell
      Carcinoma of the Scalp.

PMID- 27896205
TI  - Congenital Multiple Metatarsal Synostoses with Proximal Phalangeal Deformities of
      the Foot.

PMID- 27896206
TI  - Early Vascularized Fibular Grafts in Infants with Congenital Pseudarthrosis.

PMID- 27896207
TI  - Reader's Forum.

PMID- 27896208
TI  - Relationship between maturation indices and morphology of the midpalatal suture
      obtained using cone-beam computed tomography images.
AB  - OBJECTIVE: The purpose of this study was to determine whether predicting
      maturation of the midpalatal suture is possible by classifying its morphology on
      cone-beam computed tomography (CBCT) images and to investigate relationships with
      other developmental age indices. METHODS: The morphology of the midpalatal suture
      was assessed by using CBCT images of 99 patients. Axial plane images of the
      midpalatal suture were classified into five stages according to the
      classification scheme. To make the assessment more accurate, the morphology and
      fusion of the midpalatal suture were additionally investigated on coronal cross
      sectional planar images and volume-rendered images. Bone age was evaluated using
      the hand and wrist method (HWM) and cervical vertebrae method (CVM); dental age
      (Hellman's index), sex, and chronological age were also assessed. To evaluate
      relationships among variables, Spearman's rho rank test was performed along with
      crosstabs using contingency coefficients. RESULTS: The HWM and CVM showed strong
      correlations with the maturation stage of the midpalatal suture, while other
      indices showed relatively weak correlations (p < 0.01). Through crosstabs, the
      HWM and CVM showed high association values with CBCT stage; the HWM demonstrated
      slightly higher values (p < 0.0001). Based on the HWM, the midpalatal suture was
      not fused until stage 6 in both sexes. CONCLUSIONS: Among developmental age
      indices, the HWM and CVM showed strong correlations and high associations,
      suggesting that they can be useful in assessing maturation of the midpalatal
      suture.

PMID- 27896209
TI  - Reference points suitable for evaluation of the additional arch length required
      for leveling the curve of Spee.
AB  - OBJECTIVE: The additional arch length required for leveling (AALL) the curve of
      Spee (COS) can be estimated by subtracting the two-dimensional (2D) arch
      circumference, which is the projection of the three-dimensional (3D) arch
      circumference onto the occlusal plane, from the 3D arch circumference, which
      represents the arch length after leveling the COS. The purpose of this study was
      to determine whether the cusp tips or proximal maximum convexities are more
      appropriate reference points for estimating the AALL. METHODS: Sixteen model
      setups of the mandibular arch with COS depths ranging from 0 mm to 4.7 mm were
      constructed using digital simulation. Arch circumferences in 2D and 3D were
      measured from the cusp tips and proximal maximum convexities and used to
      calculate the AALL. The values obtained using the two reference points were
      compared with the paired t-test. RESULTS: Although the 3D arch circumference
      should be constant regardless of the COS depth, it decreased by 3.8 mm in cusp
      tip measurements and by 0.4 mm in proximal maximum convexity measurements as the
      COS deepened to 4.7 mm. AALL values calculated using the cusp tips as reference
      points were significantly smaller than those calculated using the proximal
      maximum convexities (p = 0.002). CONCLUSIONS: The AALL is underestimated when the
      cusp tips are used as measurement reference points; the AALL can be measured more
      accurately using the proximal maximum convexities.

PMID- 27896210
TI  - Comparison of the bonding strengths of second- and third-generation light
      emitting diode light-curing units.
AB  - OBJECTIVE: With the introduction of third-generation light-emitting diodes (LEDs)
      in dental practice, it is necessary to compare their bracket-bonding effects,
      safety, and efficacy with those of the second-generation units. METHODS: In this
      study, 80 extracted human premolars were randomly divided into eight groups of 10
      samples each. Metal or polycrystalline ceramic brackets were bonded on the teeth
      using second- or third-generation LED light-curing units (LCUs), according to the
      manufacturers' instructions. The shear bond strengths were measured using the
      universal testing machine, and the adhesive remnant index (ARI) was scored by
      assessing the residual resin on the surfaces of debonded teeth using a scanning
      electron microscope. In addition, curing times were also measured. RESULTS: The
      shear bond strengths in all experimental groups were higher than the acceptable
      clinical shear bond strengths, regardless of the curing unit used. In both LED
      LCU groups, all ceramic bracket groups showed significantly higher shear bond
      strengths than did the metal bracket groups except the plasma emulation group
      which showed no significant difference. When comparing units within the same
      bracket type, no differences in shear bond strength were observed between the
      second- and third-generation unit groups. Additionally, no significant
      differences were observed among the groups for the ARI. CONCLUSIONS: The bracket
      bonding effects and ARIs of second- and third-generation LED LCUs showed few
      differences, and most were without statistical significance; however, the curing
      time was shorter for the second-generation unit.

PMID- 27896211
TI  - Comparison of postoperative changes in the distal and proximal segments between
      conventional and sliding mini-plate fixation following mandibular setback.
AB  - OBJECTIVE: The purpose of the present study was to evaluate the postoperative
      three-dimensional (3D) changes in the proximal segments after mandibular setback
      sagittal split ramus osteotomy and to compare the changes between the
      conventional mini-plate fixation and semi-rigid sliding plate fixation. METHODS:
      Cone-beam computed tomography (CBCT) images were used to evaluate the
      postoperative 3D changes in the proximal segments during the healing process.
      CBCT images were superimposed using the symphysis and the lower anterior mandible
      as references. RESULTS: There were no statistically significant differences
      between the conventional mini-plate and semi-rigid sliding plate groups (p >
      0.05). With respect to the distribution of changes greater than 2 mm in the
      landmarks, the right condylion, right coronoid process, and left condylion showed
      ratios of 55.6%, 50.0%, and 44.4%, respectively, in the semi-rigid sliding plate
      group; however, none of the landmarks showed ratios greater than 30% in the
      conventional mini-plate group. CONCLUSIONS: There were no statistically
      significant differences in postoperative changes in the segments between the
      conventional mini-plate and semi-rigid sliding plate groups. Nevertheless, while
      selecting the type of fixation technique, clinicians should consider that
      landmarks with greater than 2 mm changes were higher in the semi-rigid sliding
      plate group than in the conventional mini-plate group.

PMID- 27896212
TI  - Effect of slow forced eruption on the vertical levels of the interproximal bone
      and papilla and the width of the alveolar ridge.
AB  - OBJECTIVE: Forced eruption has been proposed for the reconstruction of deficient
      bone and soft tissue. The aim of this study was to examine the changes in the
      alveolar ridge width and the vertical levels of the interproximal bone and
      papilla following forced eruption. METHODS: Patients whose hopeless maxillary
      anterior teeth were expected to undergo severe bone resorption and soft tissue
      recession upon extraction were recruited. In addition, patients whose maxillary
      anterior teeth required forced eruption for restoration due to tooth fracture or
      dental caries were included. Before and after forced eruption, the interproximal
      bone height was measured by radiographic analysis, and changes in the alveolar
      ridge width and the interproximal papilla height were measured with an acrylic
      stent. RESULTS: This prospective study demonstrated that the levels of the
      interproximal alveolar bone and papilla were significantly increased by 1.36 mm
      and 1.09 mm, respectively, in the vertical direction. However, the alveolar ridge
      width was significantly reduced by an average of 0.67 mm in the buccolingual
      direction. The changes in the level of the interproximal alveolar bone and
      papilla were positively correlated. CONCLUSIONS: Although the levels of the
      interproximal bone and papilla were significantly increased, the alveolar ridge
      width was significantly decreased following forced eruption. There was a modest
      positive and significant correlation between the changes in the height of the
      interproximal alveolar bone and the papilla. Based on our findings, modification
      of vertical forced eruption should be considered when augmentation of the
      alveolar ridge width is required.

PMID- 27896213
TI  - Bone cutting capacity and osseointegration of surface-treated orthodontic mini
      implants.
AB  - OBJECTIVE: The objective of the study was to evaluate the practicality and the
      validity of different surface treatments of self-drilling orthodontic mini
      implants (OMIs) by comparing bone cutting capacity and osseointegration. METHODS:
      Self-drilling OMIs were surface-treated in three ways: Acid etched (Etched),
      resorbable blasting media (RBM), partially resorbabla balsting media (Hybrid). We
      compared the bone cutting capacity by measuring insertion depths into artificial
      bone (polyurethane foam). To compare osseointegration, OMIs were placed in the
      tibia of 25 rabbits and the removal torque value was measured at 1, 2, 4, and 8
      weeks after placement. The specimens were analyzed by optical microscopy,
      scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy
      (EDS). RESULTS: The bone cutting capacity of the etched and hybrid group was
      lower than the machined (control) group, and was most inhibited in the RBM group
      (p < 0.05). At 4 weeks, the removal torque in the machined group was
      significantly decreased (p < 0.05), but was increased in the etched group (p <
      0.05). In the hybrid group, the removal torque significantly increased at 2
      weeks, and was the highest among all measured values at 8 weeks (p < 0.05). The
      infiltration of bone-like tissue surface was evaluated by SEM, and calcium and
      phosphorus were detected via EDS only in the hybrid group. CONCLUSIONS: Partial
      RBM surface treatment (hybrid type in this study) produced the most stable self
      drilling OMIs, without a corresponding reduction in bone cutting capacity.

PMID- 27896214
TI  - A case of severe mandibular retrognathism with bilateral condylar deformities
      treated with Le Fort I osteotomy and two advancement genioplasty procedures.
AB  - We report a case involving a young female patient with severe mandibular
      retrognathism accompanied by mandibular condylar deformity that was effectively
      treated with Le Fort I osteotomy and two genioplasty procedures. At 9 years and 9
      months of age, she was diagnosed with Angle Class III malocclusion, a skeletal
      Class II jaw relationship, an anterior crossbite, congenital absence of some
      teeth, and a left-sided cleft lip and palate. Although the anterior crossbite and
      narrow maxillary arch were corrected by interceptive orthodontic treatment,
      severe mandibular hypogrowth resulted in unexpectedly severe mandibular
      retrognathism after growth completion. Moreover, bilateral condylar deformities
      were observed, and we suspected progressive condylar resorption (PCR). There was
      a high risk of further condylar resorption with mandibular advancement surgery;
      therefore, Le Fort I osteotomy with two genioplasty procedures was performed to
      achieve counterclockwise rotation of the mandible and avoid ingravescence of the
      condylar deformities. The total duration of active treatment was 42 months. The
      maxilla was impacted by 7.0 mm and 5.0 mm in the incisor and molar regions,
      respectively, while the pogonion was advanced by 18.0 mm. This significantly
      resolved both skeletal disharmony and malocclusion. Furthermore, the hyoid bone
      was advanced, the pharyngeal airway space was increased, and the morphology of
      the mandibular condyle was maintained. At the 30-month follow-up examination, the
      patient exhibited a satisfactory facial profile. The findings from our case
      suggest that severe mandibular retrognathism with condylar deformities can be
      effectively treated without surgical mandibular advancement, thus decreasing the
      risk of PCR.

PMID- 27896215
TI  - List of the international reviewers in 2016.

PMID- 27896216
TI  - Recent Advances in Immunotherapy in Metastatic NSCLC.
AB  - Non-small cell lung cancer (NSCLC) is one of most common malignancies and the
      leading cause of cancer deaths worldwide. Despite advances in targeted therapies,
      majority of NSCLC patients do not have targetable genomic alterations.
      Nevertheless, recent discovery that NSCLC is an immunogenic tumor type, and
      several breakthroughs in immunotherapies have led to rapid expansion of this new
      treatment modality in NSCLC with recent FDA approvals of programed death receptor
      1 inhibitors, such as nivolumab and pembrolizumab. Here, we review promising
      immunotherapeutic approaches in metastatic NSCLC, including checkpoint
      inhibitors, agents with other mechanisms of action, and immunotherapy
      combinations with other drugs. With advent of immunotherapy, therapeutic options
      in metastatic NSCLC are rapidly expanding with the hope to further expand life
      expectancy in metastatic lung cancer.

PMID- 27896219
TI  - Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The
      Autophagy Connection.
AB  - Preclinical studies suggest that fasting prior to chemotherapy may be an
      effective strategy to protect patients against the adverse effects of chemo
      toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further
      suggested that fasting may similarly augment the efficacy of oncolytic viral
      therapy. The primary mechanism mediating these beneficial effects is thought to
      relate to the fact that fasting results in a decrease of circulating growth
      factors. In turn, such fasting cues would prompt normal cells to redirect energy
      toward cell maintenance and repair processes, rather than growth and
      proliferation. However, fasting is also known to upregulate autophagy, an
      evolutionarily conserved catabolic process that is upregulated in response to
      various cell stressors. Here, we review a number of mechanisms by which fasting
      induced autophagy may have an impact on both chemo-tolerance and chemo
      sensitization. First, fasting may exert a protective effect by mobilizing
      autophagic components prior to chemo-induction. In turn, the autophagic apparatus
      can be repurposed for removing cellular components damaged by chemotherapy.
      Autophagy also plays a key role in epitope expression as well as in modulating
      inflammation. Chemo-sensitization resulting from fasting may in fact be an effect
      of enhanced immune surveillance as a result of better autophagy-dependent epitope
      processing. Finally, autophagy is involved in host defense against viruses, and
      aspects of the autophagic process are also often targets for viral subversion.
      Consequently, altering autophagic flux by fasting may alter viral infectivity.
      These observations suggest that fasting-induced autophagy may have an impact on
      therapeutic efficacy in various oncological contexts.

PMID- 27896218
TI  - Hormonal Modulation of Breast Cancer Gene Expression: Implications for Intrinsic
      Subtyping in Premenopausal Women.
AB  - Clinics are increasingly adopting gene-expression profiling to diagnose breast
      cancer subtype, providing an intrinsic, molecular portrait of the tumor. For
      example, the PAM50-based Prosigna test quantifies expression of 50 key genes to
      classify breast cancer subtype, and this method of classification has been
      demonstrated to be superior over traditional immunohistochemical methods that
      detect proteins, to predict risk of disease recurrence. However, these tests were
      largely developed and validated using breast cancer samples from postmenopausal
      women. Thus, the accuracy of such tests has not been explored in the context of
      the hormonal fluctuations in estrogen and progesterone that occur during the
      menstrual cycle in premenopausal women. Concordance between traditional methods
      of subtyping and the new tests in premenopausal women is likely to depend on the
      stage of the menstrual cycle at which the tissue sample is taken and the relative
      effect of hormones on expression of genes versus proteins. The lack of knowledge
      around the effect of fluctuating estrogen and progesterone on gene expression in
      breast cancer patients raises serious concerns for intrinsic subtyping in
      premenopausal women, which comprise about 25% of breast cancer diagnoses. Further
      research on the impact of the menstrual cycle on intrinsic breast cancer
      profiling is required if premenopausal women are to benefit from the new
      technology of intrinsic subtyping.

PMID- 27896221
TI  - Microvascular Blood Flow Improvement in Hyperglycemic Obese Adult Patients by
      Hypocaloric Diet.
AB  - The present study was aimed to assess the changes in skin microvascular blood
      flow (SBF) in newly diagnosed hyperglycemic obese subjects, administered with
      hypocaloric diet. Adult patients were recruited and divided in three groups: NW
      group (n=54), NG (n=54) and HG (n=54) groups were constituted by normal weight,
      normoglycemic and hyperglycemic obese subjects, respectively. SBF was measured by
      laser Doppler perfusion monitoring technique and oscillations in blood flow were
      analyzed by spectral methods under baseline conditions, at 3 and 6 months of
      dietary treatment. Under resting conditions, SBF was lower in HG group than in NG
      and NW ones. Moreover, all subjects showed blood flow oscillations with several
      frequency components. In particular, hyperglycemic obese patients revealed lower
      spectral density in myogenic-related component than normoglycemic obese and
      normal weight ones. Moreover, post-occlusive reactive hyperemia (PORH) was
      impaired in hyperglycemic obese compared to normoglycemic and normal weigh
      subjects. After hypocaloric diet, in hyperglycemic obese patients there was an
      improvement in SBF accompanied by recovery in myogenic-related oscillations and
      arteriolar responses during PORH. In conclusion, hyperglycemia markedly affected
      peripheral microvascular function; hypocaloric diet ameliorated tissue blood
      flow.

PMID- 27896217
TI  - Adapt, Recycle, and Move on: Proteostasis and Trafficking Mechanisms in Melanoma.
AB  - Melanoma has emerged as a paradigm of a highly aggressive and plastic cancer,
      capable to co-opt the tumor stroma in order to adapt to the hostile
      microenvironment, suppress immunosurveillance mechanisms, and disseminate. In
      particular, oncogene- and aneuploidy-driven dysregulations of proteostasis in
      melanoma cells impose a rewiring of central proteostatic processes, such as the
      heat shock and unfolded protein responses, autophagy, and the endo-lysosomal
      system, to avoid proteotoxicity. Research over the past decade has indicated that
      alterations in key nodes of these proteostasis pathways act in conjunction with
      crucial oncogenic drivers to increase intrinsic adaptations of melanoma cells
      against proteotoxic stress, modulate the high metabolic demand of these cancer
      cells and the interface with other stromal cells, through the heightened release
      of soluble factors or exosomes. Here, we overview and discuss how key
      proteostasis pathways and vesicular trafficking mechanisms are turned into vital
      conduits of melanoma progression, by supporting cancer cell's adaptation to the
      microenvironment, limiting or modulating the ability to respond to therapy and
      fueling melanoma dissemination.

PMID- 27896222
TI  - 67 kDa laminin receptor (67LR) in normal and neoplastic hematopoietic cells: is
      its targeting a feasible approach?
AB  - The 67 kDa laminin receptor (67LR) is a non-integrin cell surface receptor for
      laminin (LM) that derives from a 37 kDa precursor (37LRP). 67LR expression is
      increased in neoplastic cells and correlates with an enhanced invasive and
      metastatic potentialin many human solid tumors, recommending this receptor as a
      new promising target for cancer therapy. This is supported by in vivo studies
      showing that 67LR downregulation reduces tumour cell proliferation and tumour
      formation by inducing apoptosis. 67LR association with the anti-apoptotic protein
      PED/PEA-15 activates a signal transduction pathway, leading to cell proliferation
      and resistance to apoptosis. However, the main function of 67LR is to enhance
      tumor cell adhesion to the LM of basement membranes and cell migration, two
      crucial events in the metastasis cascade. Thus, inhibition of 67LR binding to LM
      has been proved to be a feasible approach to block metastatic cancer cell spread.
      Despite accumulating evidences on 67LR overexpression in hematologic
      malignancies, 67LR role in these diseases has not been clearly defined. Here, we
      review 67LR expression and function in normal and malignant hematopoietic cells,
      67LR role and prognostic impact in hematological malignancies and first attempts
      in targeting its activity.

PMID- 27896223
TI  - Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target
      in cancer.
AB  - The urokinase (uPA)-type plasminogen activator receptor (uPAR) is a GPI-anchored
      receptor that focuses urokinase (uPA) proteolytic activity on the cell surface.
      uPAR also regulates cell adhesion, migration and proliferation, protects from
      apoptosis and contributes to epithelial mesenchymal transition (EMT),
      independently of uPA enzymatic activity. Indeed, uPAR interacts with beta1, beta2
      and beta3 integrins, thus regulating their activities. uPAR cross-talks with
      receptor tyrosine kinases through integrins and regulates cancer cell dormancy,
      proliferation and angiogenesis. Moreover, uPAR mediates uPA-dependent cell
      migration and chemotaxis induced by fMet-Leu-Phe (fMLF), through its association
      with fMLF-receptors (fMLF-Rs). Further, uPAR is an adhesion receptor because it
      binds vitronectin (VN), a component of provisional extracellular matrix. High
      uPAR expression predicts for more aggressive disease in several cancer types for
      its ability to increase invasion and metastasis. In fact, uPAR has been
      hypothesized to be the link between tumor cell dormancy and proliferation that
      usually precedes the onset of metastasis. Thus, inhibiting uPAR could be a
      feasible approach to affect tumor growth and metastasis. Here, we review the more
      recent advances in the development of uPAR-targeted anti-cancer therapeutic
      agents suitable for further optimization or ready for the evaluation in early
      clinical trials.

PMID- 27896225
TI  - The Urokinase/Urokinase Receptor System in Mast Cells: Effects of its Functional
      Interaction with fMLF Receptors.
AB  - Mast cell and basophils express the high affinity receptor for IgE (FcERI) and
      are primary effector cells of allergic disorders. The urokinase (uPA)-mediated
      plasminogen activation system is involved in physiological and pathological
      events based on cell migration and tissue remodelling, such as inflammation,
      wound healing, angiogenesis and metastasis. uPA is a serine protease that binds
      uPAR, a high affinity glycosyl-phosphatidyl-inositol (GPI)-anchored receptor.
      uPAR focuses uPA activity at the cell surface and activates intracellular
      signaling through lateral interactions with integrins, receptor tyrosine kinases
      and the G-protein-coupled family of fMLF chemotaxis receptors (FPRs). We
      investigated the expression of the uPA-uPAR system and its functional interaction
      with FPRs in human mast cells (MCs). Differently from basophils, MCs produced uPA
      that was able to induce their chemotaxis. Indeed, MCs also expressed uPAR, both
      in the intact and in a cleaved form (DII-DIII-uPAR) that can expose, at the N
      terminus, the SRSRY sequence, able to interact with FPRs and to mediate cell
      chemotaxis. MCs also expressed mRNAs for FPRs that were functionally active;
      indeed, uPA and a soluble peptide (uPAR84-95), containing the SRSRY chemotactic
      sequence of uPAR and able to interact with FPRs, were able to induce MCs
      chemotaxis. Thus, uPA is a potent chemoattractant for MCs acting through the
      exposure of the chemotactic epitope of uPAR, that is an endogenous ligand for
      FPRs. The same mechanism could be involved in VEGF-A secretion by human MCs, also
      induced by uPA and uPAR84-95 stimulation.

PMID- 27896226
TI  - Use of the directional atherectomy for the treatment of femoro-popliteal lesions
      in patients with critical lower limb ischemia.
AB  - : Femoro-popliteal PTA for the treatment of critical limb ischemia is frequently
      associated with unsatisfactory procedural success rates while directional
      atherectomy (DCA) has improved success rate since claudicant patients undergoing
      percutaneous treatment of femoro-popliteal obstructive disease. The aim of this
      prospective study is to evaluate the safety, efficacy and procedural success of
      DCA, at one year, in the percutaneous treatment of femoro-popliteal obstructive
      disease in patients with critical limb ischemia. METHODS: From March 2012 to
      March 2013 18 consecutive patients with critical limb ischemia were treated with
      DCA (Turbohawk/Covidien-ev3 Endovascular Inc., North Plymouth, Minnesota, USA)
      for the treatment of femoro-popliteal obstructive disease. Patients were
      evaluated at 12 months. RESULTS: Technical and procedural success was achieved in
      every patient. No in-hospital major adverse cardiovascular events occurred.
      Primary endpoint: freedom from any amputation was obtained in all patients.
      Secondary endpoints: clinical (Rutherford class improvement) and hemodynamic
      success (Ankle-brachial index improvement) was achieved in all patients.
      CONCLUSION: The use of DCA for the treatment of femoro-popliteal obstructive
      disease is a safe and effective therapeutic strategy for patients with critical
      limb ischemia. The data included in our study should be considered hypothesis
      generating in order to design of a randomized trial comparison with conventional
      PTA.

PMID- 27896224
TI  - In Vitro Apoptotic Effects of Farnesyltransferase blockade in Acute Myeloid
      Leukemia Cells.
AB  - Farnesyltransferase inhibitors (FTIs) are a class of oral anti-cancer drugs
      currently tested in phase I-II clinical trials for treatment of hematological
      malignancies. The in vitro effects of various FTIs (alpha
      hydroxyfarnesylphosphonic acid, manumycin-A and SCH66336) were tested on CD34+
      KG1a cell line and in primary acute myeloid leukemia (AML) cells from 64
      patients. By cell viability and clonogeneic methylcellulose assays, FTIs showed a
      significant inhibitory activity in CD34+ KG1a and primary bone marrow (BM)
      leukemic cells from 56% of AML patients. FTIs also induced activation of caspase
      3 and Fas-independent apoptosis, confirmed by the finding that inhibition of
      caspase-8 was not associated with the rescue of FTI-treated cells. We concluded
      that other cellular events induced by FTIs may trigger activation of caspase-3
      and subsequent apoptosis, but the expression of proapoptotic molecules, as Bcl-2
      and Bcl-XL, and antiapoptotic, as Bcl-X(s), were not modified by FTIs. By
      contrast, expression of inducible nitric oxide synthase (iNOS) was increased in
      FTI-treated AML cells. Our results suggest a very complex mechanism of action of
      FTIs that require more studies for a better clinical use of the drugs alone or in
      combination in the treatment of hematological malignancies.

PMID- 27896227
TI  - Stress-first single photon emission computed myocardial perfusion imaging.
AB  - BACKGROUND: Myocardial perfusion imaging (MPI) with single photon emission
      tomography (SPET) is widely used in coronary artery disease evaluation. Recently
      major dosimetric concerns have arisen. The aim of this study was to evaluate if a
      pre-test scoring system could predict the results of stress SPET MPI, thus
      avoiding two radionuclide injections. METHODS: All consecutive patients (n=309)
      undergoing SPET MPI during the first 6 months of 2014 constituted the study
      group. The scoring system is based on these characteristics: age >65 years (1
      point), diabetes (2 points), typical chest pain (2 points), congestive heart
      failure (3 points), abnormal ECG (4 points), male gender (4 points), and
      documented previous CAD (5 points). The patients were divided on the basis of the
      prediction score into 3 classes of risk for an abnormal stress-first protocol.
      RESULTS: An abnormal stress SPET MPI was present in 7/31 patients (23%) with a
      low risk score, in 24/90 (27%) with an intermediate score risk, and in 124/188
      (66%) with an high score risk. ROC curve analysis showed good prediction of
      abnormal stress MPI. CONCLUSIONS: Our results suggest an appropriate use of a pre
      test clinical prediction formula of abnormal stress MPI in a routine clinical
      setting.

PMID- 27896220
TI  - Anti-Immune Strategies of Pathogenic Fungi.
AB  - Pathogenic fungi have developed many strategies to evade the host immune system.
      Multiple escape mechanisms appear to function together to inhibit attack by the
      various stages of both the adaptive and the innate immune response. Thus, after
      entering the host, such pathogens fight to overcome the immune system to allow
      their survival, colonization and spread to different sites of infection.
      Consequently, the establishment of a successful infectious process is closely
      related to the ability of the pathogen to modulate attack by the immune system.
      Most strategies employed to subvert or exploit the immune system are shared among
      different species of fungi. In this review, we summarize the main strategies
      employed for immune evasion by some of the major pathogenic fungi.

PMID- 27896228
TI  - The European Innovation Partnership on Active and Healthy Ageing Synergies:
      Protocol for a Prospective Observational Study to Measure the Impact of a
      Community-Based Program on Prevention and Mitigation of Frailty (ICP - PMF) in
      Community-Dwelling Older Adults.
AB  - Aim of this paper is to describe the protocol of the study "Impact of a Community
      based Program on Prevention and Mitigation of Frailty in community-dwelling older
      adults" developed in the framework of the European Innovation Partnership on
      Active and Healthy Ageing. This proposal has been developed by the Partnership
      Action groups on frailty, fall prevention and polypharmacy in older. The proposal
      wants to assess the impact of community-based programs aimed to counteract three
      main outcomes related to frailty: hospitalization, institutionalization and
      death. Bringing together researchers from seven European countries, the proposal
      aims to achieve the critical mass and the geographical extension enough to
      provide information useful to all older European citizens. An observational study
      will be carried out to calculate the incidence of the different outcomes in
      relation to the various interventions that will be assessed; results will be
      compared with data coming from already established national, regional and local
      dataset using the observed/expected approach. The sample will be made up by at
      least 2000 citizens for each outcome. All the citizens will be assessed at the
      baseline with two multidimensional questionnaires: the RISC questionnaire and the
      Short Functional Geriatric Evaluation questionnaire. The outcomes will be
      assessed every six-twelve months.

PMID- 27896229
TI  - Effect Of alpha2-Adrenergic Agonists And Antagonists On Cytokine Release From
      Human Lung Macrophages Cultured In Vitro.
AB  - The most trusted hypothesis to explain how alpha2-adrenergic agonists may
      preserve pulmonary functions in critically ill patients is that they directly act
      on macrophages by interfering with an autocrine/paracrine adrenergic system that
      controls cytokine release through locally synthetized noradrenaline and alpha1-
      and alpha2-adrenoreceptors. We tested this hypothesis in primary cultures of
      resident macrophages from human lung (HLMs). HLMs were isolated by centrifugation
      on percoll gradients from macroscopically healthy human lung tissue obtained from
      four different patients at the time of lung resection for cancer. HLMs from these
      patients showed a significant expression of alpha2A, alpha2B and alpha2C
      adrenoreceptors both at the mRNA and at the protein level. To evaluate whether
      alpha2 adrenoreceptors controlled cytokine release from HMLs, we measured IL-6,
      IL-8 and TNF-alpha concentrations in the culture medium in basal conditions and
      after preincubation with several alpha2-adrenergic agonists or antagonists.
      Neither the pretreatment with the alpha2-adrenergic agonists clonidine,
      medetomidine or dexdemetomidine or with the alpha2-adrenergic antagonist
      yohimbine caused significant changes in the response of any of these cytokines to
      LPS. These results show that, different from what reported in rodents, clonidine
      and dexdemetomidine do not directly suppress cytokine release from human
      pulmonary macrophages. This suggests that alternative mechanisms such as effects
      on immune cells activation or the modulation of autonomic neurotransmission could
      be responsible for the beneficial effects of these drugs on lung function in
      critical patients.

PMID- 27896230
TI  - Evaluation of Symptoms and Prevention of Cancer in Menopause: The Value of Vulvar
      Exam.
AB  - Vulvar and vaginal atrophy (VVA), is a chronic medical condition experienced by
      postmenopausal women, with prevalence estimated ranging from 10% to 50% [1]. VVA
      is characterized by a constellation of symptoms, that may affect daily
      activities, sexuality, relationships, and quality of life [3]. Early recognition
      and effective treatment of VVA may enhance sexual health and the quality of life
      of women and their partners. Some vulvar conditions such as lichen sclerosus are
      more prevalent in the postmenopausal years. Lichen sclerosus has been suggested
      as a precursor of Vulvar squamous cell carcinoma. The vulvar exam in post
      menopausal women plays an essential role in prevention of cancer because it
      allows to identify women who should undergo vulvar skin biopsy in order to early
      detect pre-neoplastic lesions for early diagnosis of cancer of the vulva.

PMID- 27896231
TI  - Prolonged complete hematologic response in relapsed/refractory T-large granular
      lymphocyte leukemia after bendamustine treatment.
AB  - T-large granular lymphocyte leukemia (T-LGLL) is a chronic clonal proliferation
      of effector memory cytotoxic CD3+CD57+CD56- T cells and the current guidelines
      suggest immunosuppressive therapy as first-line therapy, but the treatment of
      refractory/relapsed patients is still challenging due to the lack of prospective
      studies. We describe a series of two refractory/relapsed T-LGLL patients
      successfully treated with bendamustine, a chemotherapeutic agent largely used for
      B-cell neoplasms, but poorly investigated for the treatment of T-cell diseases.
      Complete remission (CR) was achieved in 3 and 6 months, respectively, and
      maintained for at least 20 months. One patient relapsed after a 20-month CR, but
      she was responsive to bendamustine therapy again, obtaining a further prolonged
      CR. Bendamustine as single agent or in combination could be a feasible
      therapeutic option in refractory/relapsed T-LGLL, especially for elderly patients
      because of its safety profile.

PMID- 27896232
TI  - Quality of life perception in type 2 diabetes.
AB  - PURPOSE: Lifestyle analysis is often used for primary and secondary prevention in
      many chronic metabolic diseases, including diabetes. Questionnaires are simple
      and common methods for first investigation risk of factors related to the
      perception of quality of life (QoL). The present study evaluates the feasibility
      to use questionnaires for first investigation of risk factors, and ascertain
      whether the results of such questionnaires are associated with the perception of
      QoL. METHODS: Validated questionnaires from the international ACSM guidelines
      were used to study a cohort of 142 consecutive type 2 diabetes patients (mean
      age: 66.1 years +/- 10.9). RESULTS: QoL perception was normal; BMI was compatible
      with overweight in 79.1% of subjects, and obesity in 20.9%. Cognitive abilities
      decreased with age and low consumption of dried fruit and legumes. There was
      evidence of a statistically significant association between BMI and QoL (rho = 
      0.18; p = 0.03). CONCLUSIONS: Questionnaires are useful to assess lifestyle
      habits and highlight risks factors. Poor knowledge of patients' own chronic
      disease may contribute to a negative impact in diabetes.

PMID- 27896233
TI  - Serum fructosamine, serum glycated albumin and serum glycated beta-lipoprotein in
      type 2 diabetes mellitus patients with and without microvascular complications.
AB  - BACKGROUND: Glycation of serum proteins has been proposed as an important
      mechanism of complications of diabetes but whether there are differences in
      glycation of different serum proteins and whether it has any correlation with
      development of microvascular complications has not been studied in depth. This
      study aimed to assess level of serum fructosamine, glycated albumin and glycated
      beta-lipoprotein in type 2 diabetes mellitus patients with and without
      microvascular complications and to find out their correlation with diabetes
      complications. METHODS: Case-control study involving 150 individuals at a
      tertiary care hospital in western India. Fifty participants were healthy controls
      (group 1), 50 were type 2 diabetes patients without any evident microvascular
      complication (group 2) and 50 were type 2 diabetes patients with one or more
      microvascular complications (group 3). Serum fructosamine, FBS, PP2BS and other
      biochemical parameters were measured. Glycated albumin and glycated beta
      lipoprotein were measured by agarose gel electrophoresis followed by NBT
      staining. Unpaired t-test was used to find out significance of difference between
      two groups and correlation coefficient to find out statistical correlation
      between two variables. RESULTS: Type 2 diabetes patients with one or more
      microvascular complications had poor glycemic control as indicated by markers of
      short and mid-term glycemia. Differences between the groups for fructosamine,
      glycated albumin and glycated beta-lipoprotein were significant (p < 0.001).
      Glycated albumin correlated with FBS, PP2BS and fructosamine in all diabetic
      patients (group 2 and 3) whereas glycated beta-lipoprotein correlated with these
      parameters only in group 3 and it was markedly elevated in group 3. CONCLUSION:
      Serum glycated beta-lipoprotein was disproportionately elevated compared to
      fructosamine and glycated albumin in diabetes patients with microvascular
      complications (group 3) and it correlated with rest of glycemic markers only in
      this group. Glycated beta-lipoprotein might help in identifying diabetic
      individuals at high future risk of developing microvascular complications.

PMID- 27896234
TI  - Frequency and Associated Factors of Amphotericin B Nephrotoxicity in Hospitalized
      Patients in Hematology-Oncology Wards in the Southwest of Iran.
AB  - BACKGROUND: Nephrotoxicity is the most clinically significant adverse reaction of
      amphotericin B. Different aspects of amphotericin B (AmB) nephrotoxicity have not
      been studied well in our population. OBJECTIVES: The purpose of this study was to
      assess the frequency, time onset, and possible associated factors of AmB
      nephrotoxicity in hospitalized patients in hematology-oncology wards in the
      southwest of Iran. PATIENTS AND METHODS: A cross-sectional, observational study
      was performed over a period of 9 months at 2 hematology-oncology and 1
      hematopoietic stem cell transplantation wards at Namazi Hospital. Patients aged
      15 years or older with no documented history of acute kidney injury or chronic
      kidney disease who were scheduled to receive formulations of AmB intravenously
      for at least 1 week were included. The required demographic and clinical data of
      the patients were recorded. Urine urea, creatinine, sodium, potassium, and
      magnesium levels were measured at days 0, 3, 5, 7, 10, and 14 of the AmB
      treatment. AmB nephrotoxicity based on serum creatinine increase, renal potassium
      wasting, hypokalemia, and hypomagnesemia were determined. RESULTS: Among the 40
      patients recruited for the study, 11 (27.5%) patients developed AmB
      nephrotoxicity with a mean +/- standard deviation onset of 6.73 +/- 2.36 days. In
      5 patients, AmB nephrotoxicity resolved spontaneously without any intervention.
      According to the multivariate logistic regression model, none of the studied
      demographic, clinical, and paraclinical variables were significantly associated
      with AmB nephrotoxicity. The duration of hospitalization (P = 0.541) and the
      mortality rate (P = 0.723) were comparable between the patients with and without
      AmB nephrotoxicity. Hypokalemia and renal potassium wasting were identified in
      45% and 27.5% of the patients during AmB treatment, respectively. CONCLUSIONS:
      Nearly one-third (27.5%) of our cohort developed nephrotoxicity within the first
      week of AmB treatment. Hypokalemia and renal potassium wasting were more notable,
      affecting about one-half and one-third of the AmB recipients, respectively.

PMID- 27896235
TI  - Application of Parametric Models to a Survival Analysis of Hemodialysis Patients.
AB  - BACKGROUND: Hemodialysis is the most common renal replacement therapy in patients
      with end stage renal disease (ESRD). OBJECTIVES: The present study compared the
      performance of various parametric models in a survival analysis of hemodialysis
      patients. METHODS: This study consisted of 270 hemodialysis patients who were
      referred to Imam Khomeini and Fatima Zahra hospitals between November 2007 and
      November 2012. The Akaike information criterion (AIC) and residuals review were
      used to compare the performance of the parametric models. The computations were
      done using STATA Software, with significance accepted at a level of 0.05.
      RESULTS: The results of a multivariate analysis of the variables in the
      parametric models showed that the mean serum albumin and the clinic attended were
      the most important predictors in the survival of the hemodialysis patients (P <
      0.05). Among the parametric models tested, the results indicated that the
      performance of the Weibull model was the highest. CONCLUSIONS: Parametric models
      may provide complementary data for clinicians and researchers about how risks
      vary over time. The Weibull model seemed to show the best fit among the
      parametric models of the survival of hemodialysis patients.

PMID- 27896236
TI  - The Effect of BCAA and ISO-WHEY Oral Nutritional Supplements on Dialysis
      Adequacy.
AB  - BACKGROUND: Protein-energy malnutrition is a common problem in hemodialysis
      patients and has different outcomes such as reduced quality of life, longer
      hospitalization time, lower dialysis adequacy, and higher mortality rate.
      Investigation of dialysis adequacy is an important method for assessing
      hemodialysis patients, and improving the dialysis adequacy is an important
      healthcare team goal. OBJECTIVES: The present study aims to investigate and
      compare the effects of BCAA and ISO-WHEY oral nutritional supplements on dialysis
      adequacy. METHODS: In a clinical trial study, 66 hemodialysis patients were
      randomly divided into three groups: Group A (n = 22), Group B (n = 22), and Group
      C or the control group (n = 22). In Groups A and B, as prescribed and controlled
      by nutritionists and nephrologists, respectively, ISO-WHEY and BCAA protein
      powder were used for 2 months on a daily basis. For all groups, before
      intervention and 1 and 2 months after intervention, the dialysis adequacy was
      measured using URR and Kt/V. Finally, the data were analyzed using IBM SPSS
      Statistics Base 21.0 software. RESULTS: Out of 66 patients, 61 (19 in Group A, 20
      in Group B, and 22 in Group C) completed the study period, and before
      intervention, all groups were equal in terms of quality and quantity variables (P
      > 0.05). After intervention, there was a significant difference between the three
      groups with regard to the variables of dialysis adequacy based on Kt/V and URR to
      independent-t test and repeated measures ANOVA (P < 0.05). CONCLUSIONS: Results
      show that the intake of oral nutritional supplements leads to an improvement in
      the dialysis adequacy of hemodialysis patients. Therefore, the use of nutritional
      supplements along with patients' training and regular consultation will be
      helpful in improving the nutritional status, dialysis adequacy, and eventually
      the quality of life.

PMID- 27896237
TI  - Negative Religious Coping, Positive Religious Coping, and Quality of Life Among
      Hemodialysis Patients.
AB  - BACKGROUND: Religious coping is known as a main resource influencing how
      individuals cope with the complications and stressors of chronic disease.
      OBJECTIVES: The aim of this study was to assess the relationship between
      religious coping and quality of life among hemodialysis patients. METHODS: This
      cross-sectional study was conducted in Qom, Iran, from June 2012 to July 2013.
      Ninety-five end-stage renal disease (ESRD) patients undergoing hemodialysis were
      selected via the convenience sampling method. Data were collected via a
      questionnaire comprising items on sociodemographic information, quality of life,
      the anxiety and depression scale, and religious coping. Following this, the data
      were analyzed using descriptive statistics and logistic regression analysis.
      RESULTS: The mean age of patients was 50.4 (standard deviation [SD] = 15.7)
      years, and most were male (61%). The mean score for positive religious coping was
      23.38 (SD = 4.17), while that for negative religious coping was 11.46 (SD =
      4.34). It was found that 53.6% of patients had higher than the mean score of
      positive religious coping, while those with negative religious coping made up
      37.9%. Negative religious coping was associated with worse quality of life,
      including physical functioning (odds ratio [OR] = 0.72; P = 0.009), role physical
      (OR = 0.79; P = 0.04), vitality (OR = 0.62; P = 0.005), social functioning (OR =
      0.69; P = 0.007), and mental health (OR = 0.58; P = 0.01) after controlling for
      sociodemographic, clinical, and anxiety and depression variables. CONCLUSIONS:
      The results indicated that patients with negative religious coping abilities were
      at risk of a suboptimal quality of life. Incorporating religious support in the
      care of hemodialysis patients may be helpful in improving quality of life in this
      patient population. Further longitudinal studies are needed to determine whether
      these associations are causal and the direction of effect.

PMID- 27896238
TI  - Retroperitoneal Fibrosis Due to Opium Abuse: A Case Series and Literature Review.
AB  - Retroperitoneal fibrosis (RPF) is a rare condition with an unclear etiology,
      presenting with the development of aberrant chronic nonspecific fibroinflammatory
      tissue in the retroperitoneal space, which can result in entrapment and
      obstruction of the retroperitoneal structures. RPF is a subtype of chronic
      periaortitis, and can be divided into two types: primary (or idiopathic) and
      secondary. RPF is usually idiopathic, but can also be secondary to malignancies,
      certain drugs, infections, surgery, and trauma. The systemic clinical
      manifestations are nonspecific and include low-grade fever, fatigue, anorexia,
      weight loss, and myalgia. We report five patients admitted to our hospital with
      clinical, laboratory, imaging, and pathologic findings compatible with RPF, and
      we describe their treatment and follow-up. We were suspicious that the impurities
      of some types of opium have an important role in the pathogenesis of RPF. Some of
      our patients used opium again after the follow-up period; however, they used a
      different type with a different origin, and we were surprised to see that RPF did
      not form again.

PMID- 27896239
TI  - Prostate-Specific Antigen Density and Gleason Score Predict Adverse Pathologic
      Features in Patients with Clinically Localized Prostate Cancer.
AB  - BACKGROUND: According to recent studies, prostate cancer is the second most
      common cancer among Iranian men. Radical prostatectomy has been considered the
      gold standard treatment in patients with clinically localized prostate cancer.
      Gleason score, PSA density, and PSA velocity are some of the parameters used to
      predict adverse pathologic features. OBJECTIVES: The aim of this study was to
      evaluate the prognostic value of PSA density and Gleason score in predicting
      adverse pathologic features in patients with localized prostate cancer who
      undergo radical prostatectomy. METHODS: We conducted a cross-sectional study of
      105 patients with localized prostate cancer who underwent radical prostatectomy
      between 2006 and 2013. We recorded Gleason scores and PSA levels, in addition to
      the results of pathological evaluations after radical prostatectomy, including
      prostate volume, stage, LNI (lymph node involvement), SVI (seminal vesicle
      invasion), and extraprostatic extension (EPE). Data were analyzed using SPSS
      version 21. RESULTS: Mean PSA density was 0.27 (0.17 SD). The frequencies of EPE,
      SVI, and LNI were 21.9, 16.2, and 2.9, respectively. The Mann-Whitney U-test
      demonstrated a significant correlation between PSA density and adverse pathologic
      features (EPE, SVI, and LNI). CONCLUSIONS: PSA, PSA density, and Gleason score
      should be considered together in order to more accurately predict the adverse
      pathologic features of prostate cancer.

PMID- 27896240
TI  - Evaluation of Anti-Toxoplasma gondii Antibodies in Hemodialysis Patients with
      Chronic Kidney Disease in Sari, Iran.
AB  - BACKGROUND: Toxoplasma gondii has worldwide distribution and is one of the most
      prevalent infectious agents in humans. OBJECTIVES: The aim of this study was to
      determine the prevalence of anti-Toxoplasma gondii antibodies in hemodialysis
      patients with chronic kidney disease (CKD) in the hemodialysis unit of Fatemeh
      Zahra hospital at the Mazandaran University of Medical Sciences in Sari, Iran.
      METHODS: Seventy-three patients with CKD and 145 healthy volunteers were assessed
      for anti-Toxoplasma gondii (IgG, IgM, and IgA) antibodies using a conventional
      ELISA technique. RESULTS: The anti-Toxoplasma gondii IgG antibody was detected in
      80.8% of the cases in the patient group, while 31.5% of the cases in the CKD
      patient group and 31.8% in the control group were found to be positive for the
      anti-Toxoplasma gondii IgA antibody. All the patients in the CKD group were
      negative for the anti-Toxoplasma gondii IgM antibody, although 2.76% of the
      healthy volunteers were found to be positive. The present study suggests that
      there was no significant difference between the hemodialysis patient group and
      the healthy volunteers. CONCLUSIONS: The epidemiological data collected in this
      study could serve as a reference for future studies and may be useful in
      developing preventive and educational strategies, and consequently reducing
      healthcare expenditure.

PMID- 27896241
TI  - Local Administration of Tranexamic Acid During Prostatectomy Surgery: Effects on
      Reducing the Amount of Bleeding.
AB  - BACKGROUND: One of the issues in prostatectomy surgery is bleeding. Although
      tranexamic acid (TRA) is an antifibrinolytic agent for reducing bleeding,
      controversies surround its use. OBJECTIVES: In this study, the effect of local
      administration of TRA on reducing bleeding during prostatectomy surgery was
      evaluated. METHODS: A total of 186 patients who underwent prostatectomy surgery
      were assessed in this clinical trial study. Patients were divided randomly into
      two groups. After prostate removal, TRA (500 mg TRA with 5 mL total volume) to
      the intervention group and normal saline to the control group were sprayed with
      the same volume. At the end of surgery, the prescribed blood bags were measured
      and recorded. Hemoglobin and platelet levels were recorded 6 hours after the
      test. Moreover, the amounts of blood inside the blood bags in the first 24 hours,
      the second 24 hours, and the total length of hospital stay were recorded and
      compared in each group. RESULTS: By comparing the measured values before and
      after surgery, we found that the amounts of hemoglobin, hematocrit, and platelet
      decreased. The mean blood loss in the intervention group was recorded at 340 mL
      and that in the control group was 515 mL. The maximum bleeding in the control
      group was almost twice as much as that in the intervention group. Blood loss in
      the intervention group with the administration of TRA was significantly lesser
      than that in the control group (P = 0.01). The decrease in platelet level in the
      intervention group was significantly lower than that in the control group (P =
      0.03). CONCLUSIONS: The present study showed that local administration of TRA
      significantly reduces bleeding after prostatectomy surgery and is effective in
      preventing postoperative hemoglobin decrease.

PMID- 27896242
TI  - Intracytoplasmic Sperm Injection Outcomes with Freshly Ejaculated Sperms and
      Testicular or Epididymal Sperm Extraction in Patients with Idiopathic
      Cryptozoospermia.
AB  - BACKGROUND: Cryptozoospermia (CO) is a situation in which spermatozoa cannot be
      observed in a fresh semen sample unless an extended centrifugation and
      microscopic search are performed. CO patients are suggested to use only
      intracytoplasmic sperm injection (ICSI) as infertility treatment. But still there
      is debate about the choice of sperm source in cryptozoospermic men candidate for
      ICSI. OBJECTIVES: This study was conducted to evaluate fertility outcomes in men
      with idiopathic cryptozoospermia who were treated using ICSI with freshly
      ejaculated sperm and testis sperm extraction (TESE) or percutaneous epididymal
      sperm aspiration (PESA). METHODS: In this prospective cohort study carried out in
      an academic institution, 83 out of 92 couples with cryptozoospermia undergoing
      their first ICSI cycle were recruited. These patients were randomly allocated to
      two groups: group one (n = 42) who produced freshly ejaculated sperm and, group
      two (n = 41) who produced a sample by TESE or PESA. The groups were analyzed and
      compared in terms of fertilization rate, cleavage rate, embryo quality,
      implantation rate, and clinical pregnancy rate. RESULTS: There was a significant
      difference in fertilization rate, embryo quality, implantation rate, and
      pregnancy rates between the group of surgically extracted sperm and those of
      naturally ejaculated sperm using conventional ICSI (P < 0.05). CONCLUSIONS: Sperm
      quality extracted by percutaneous PESA and TESE procedures increases fertility
      outcomes compared to naturally ejaculated sperm in men with idiopathic CO. More
      specifically, embryo quality, which is most relevant to fertility outcome,
      improved when surgically extracted sperm was used for ICSI.

PMID- 27896243
TI  - Profile of tivantinib and its potential in the treatment of hepatocellular
      carcinoma: the evidence to date.
AB  - Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related
      death in the United States and carries a very poor prognosis, with a median
      survival time of <50% at 1 year for advanced disease. To date, sorafenib is the
      only therapy approved by the Food and Drug Administration for the treatment of
      advanced HCC. Tivantinib (ARQ-197), a non-ATP competitive inhibitor of cellular
      mesenchymal-epithelial transcription factor (c-MET), has shown a survival benefit
      in patients with advanced HCC who have failed or are intolerant to sorafenib in
      Phase I and II trials. Those patients who have tumors with high concentrations of
      MET (MET-high) appear to derive the greatest benefit from tivantinib therapy.
      Currently, two large randomized double-blind placebo-controlled Phase III trials
      (METIV-HCC [NCT01755767] and JET-HCC [NCT02029157]) are evaluating tivantinib in
      patients with MET-high advanced HCC, with the primary end points of overall
      survival and progression-free survival, respectively. This study reviews the
      evidence for the use of tivantinib in advanced HCC. Specific topics addressed
      include the pharmacology, dosing, toxicity, and biomarkers associated with
      tivantinib use.

PMID- 27896244
TI  - Adaptive responses of cardiac function to fetal postural change as gestational
      age increases.
AB  - OBJECTIVE: The cardiovascular system maintains homeostasis through a series of
      adaptive responses to physiological requirements. However, little is known about
      the adaptation of fetal cardiac function to gravity, according to gestational
      age. In the present study, we aimed to evaluate the adaptive responses of cardiac
      function to postural changes, using Tei index measurements. METHODS: Fetal
      echocardiography and Doppler examination were performed on 114 women with vertex
      singleton pregnancies at 19 to 40 weeks' gestation. Participants were placed in
      an upright seated position, and the Tei index for fetal left ventricular cardiac
      function was measured. The women were then moved into a supine position and the
      Tei index was re-measured. RESULTS: The mean Tei index when measured in an
      upright seated position was significantly lower than that measured in a supine
      positioning for all fetuses (0.528+/-0.103 vs. 0.555+/-0.106, P=0.014,
      respectively). This difference was also noted in fetuses with a gestational age
      of 28-40 weeks (0.539+/-0.107 vs. 0.574+/-0.102, P=0.011, respectively). However,
      there was no difference in the Tei index between an upright seated and a supine
      position among fetuses with a gestational age of <28 weeks (0.505+/-0.091 vs.
      0.516+/-0.103, P=0.571, respectively). CONCLUSION: Postural changes from an
      upright seated to a supine position result in an increased Tei index after a
      gestational age of 28 weeks. This appears to reflect maturation in the adaptive
      responses of the fetal cardiovascular system to postural changes.

PMID- 27896245
TI  - Differences in clinical presentation and pregnancy outcomes in antepartum
      preeclampsia and new-onset postpartum preeclampsia: Are these the same disorder?
AB  - OBJECTIVE: New-onset postpartum preeclampsia is a poorly defined condition that
      accounts for a significant percentage of eclampsia cases. It is unclear whether
      new-onset postpartum preeclampsia is a different disorder from or belongs to the
      same spectrum of classic antepartum preeclampsia. The objective of this study was
      to compare the clinical presentation and pregnancy outcomes of antepartum
      preeclampsia and new-onset postpartum preeclampsia. METHODS: A retrospective
      study including 92 patients with antepartum preeclampsia and 92 patients with new
      onset postpartum preeclampsia was performed. Clinical presentation and pregnancy
      outcomes were compared. Chi-square test was used to analyze categorical
      variables, and independent t-test and Mann-Whitney U-test for numerical
      variables. P-values of <0.05 were used to indicate statistical signifi cance.
      RESULTS: Patients with antepartum preeclampsia and new-onset postpartum
      preeclampsia differ significantly in profile, symptoms at presentation,
      laboratory markers and pregnancy outcomes. CONCLUSION: New-onset postpartum
      preeclampsia has a distinct patient profile and clinical presentation than
      antepartum preeclampsia, suggesting they may represent different disorders.
      Characterization of a patient profile with increased risk of developing this
      condition will help clinicians to identify patients at risk and provide early and
      targeted interventions to decrease the morbidity associated with this condition.

PMID- 27896246
TI  - Quantitative fluorescent polymerase chain reaction for rapid prenatal diagnosis
      of fetal aneuploidies in chorionic villus sampling in a single institution.
AB  - OBJECTIVE: To validate quantitative fluorescent polymerase chain reaction (QF
      PCR) via chorionic villus sampling (CVS) for the diagnosis of fetal aneuploidies.
      METHODS: We retrospectively reviewed the medical records of consecutive pregnant
      women who had undergone CVS at Cheil General Hospital between December 2009 and
      June 2014. Only cases with reported QF-PCR before long-term culture (LTC) for
      conventional cytogenetic analysis were included, and the results of these two
      methods were compared. RESULTS: A total of 383 pregnant women underwent QF-PCR
      and LTC via CVS during the study period and 403 CVS specimens were collected. The
      indications of CVS were as follows: abnormal first-trimester ultrasonographic
      findings, including increased fetal nuchal translucency (85.1%), advanced
      maternal age (6.8%), previous history of fetal anomalies (4.2%), and positive
      dual test results for trisomy 21 (3.9%). The results of QF-PCR via CVS were as
      follows: 76 (18.9%) cases were identified as trisomy 21 (36 cases), 18 (33
      cases), or 13 (seven cases), and 4 (1.0%) cases were suspected to be mosaicism.
      All results of common autosomal trisomies by QF-PCR were consistent with those of
      LTC and there were no false-positive findings. Four cases suspected as mosaicism
      in QF-PCR were confirmed as non-mosaic trisomies of trisomy 21 (one case) or
      trisomy 18 (three cases) in LTC. CONCLUSION: QF-PCR via CVS has the advantage of
      rapid prenatal screening at an earlier stage of pregnancy for common chromosomal
      trisomies and thus can reduce the anxiety of parents. In particular, it can be
      helpful for pregnant women with increased fetal nuchal translucency or abnormal
      first-trimester ultrasonographic findings.

PMID- 27896247
TI  - Uterine rupture in pregnancies following myomectomy: A multicenter case series.
AB  - OBJECTIVE: The purpose of this case series was to retrospectively examine records
      of cases with uterine rupture in pregnancies following myomectomy and to describe
      the clinical features and pregnancy outcomes. METHODS: This study was conducted
      as a multicenter case series. The patient databases at 7 tertiary hospitals were
      queried. Records of patients with a diagnosis of uterine rupture in the pregnancy
      following myomectomy between January 2012 and December 2014 were retrospectively
      collected. The uterine rupture cases enrolled in this study were defined as
      follows: through-and-through uterine rupture or tear of the uterine muscle and
      serosa, occurrence from 24+0 to 41+6 weeks' gestation, singleton pregnancy, and
      previous laparoscopic myomectomy (LSM) or laparotomic myomectomy (LTM) status.
      RESULTS: Fourteen pregnant women experienced uterine rupture during their
      pregnancy after LSM or LTM. Preterm delivery of less than 34 weeks' gestation
      occurred in 5 cases, while intrauterine fetal death occurred in 3, and 3 cases
      had fetal distress. Of the 14 uterine rupture cases, none occurred during labor.
      All mothers survived and had no sequelae, unlike the perinatal outcomes, although
      they were receiving blood transfusion or treatment for uterine artery
      embolization because of uterine atony or massive hemorrhage. CONCLUSION: In women
      of childbearing age who are scheduled to undergo LTM or LSM, the potential risk
      of uterine rupture on subsequent pregnancy should be explained before surgery.
      Pregnancy in women after myomectomy should be carefully observed, and they should
      be adequately counseled during this period.

PMID- 27896249
TI  - Glycogen synthase kinase 3beta and cyclin D1 expression in cervical
      carcinogenesis.
AB  - OBJECTIVE: Glycogen synthase kinase 3beta (GSK3beta) is a pluripotent protein
      kinase involved in the development of cancers through regulation of numerous
      oncogenic molecules. Cyclin D1, an important regulator of G1 to S phase
      transition in various cells, is one of target proteins that GSK3beta regulate.
      Our objective was to assess the expression of GSK3beta and cyclin D1 in cervical
      neoplasm of different histologic grades and to identify their correlation in
      cervical carcinogenesis. METHODS: Immunohistochemical analysis of GSK3beta and
      cyclin D1 was performed in a total of 137 patients with 12 normal, 62 cervical
      intraepithelial neoplasia (CIN) (31 CIN1 and 31 CIN3) and 63 invasive cancers
      including 56 squamous cell carcinomas and 7 adenocarcinomas. RESULTS: The
      expression of GSK3beta increased in parallel with the lesion grade, while that of
      cyclin D1 decreased with severity of the lesion (P<0.001). There was a
      significant inverse correlation between GSK3beta and cyclin D1 expression in
      overall cervical neoplasia (Phi=-0.413, P<0.001). GSK3beta expression was higher
      in squamous cell carcinoma than in adenocarcinoma (P=0.049). CONCLUSION: These
      results suggest that the expressional increase in GSK3beta plays a role in
      cervical carcinogenesis and has inverse correlation with cyclin D1 expression in
      this process. In addition, GSK3beta expression appears to be associated with the
      histologic type of cervical cancer, especially squamous cell carcinoma.

PMID- 27896250
TI  - Clinical efficacy of photodynamic therapy.
AB  - OBJECTIVE: The management of cervical intraepithelial neoplasia (CIN) and early
      invasive cancer of the uterine cervix is very difficult to approach, especially
      in case of young woman who wants to preserve her fertility. Conization of the
      cervix may have various kinds of disadvantage. The objective of this clinical
      retrospective study is to investigate the therapeutic effects and clinical
      efficacy of photodynamic therapy (PDT) including combined chemo-photodynamic
      therapy in patients with pre-malignant CIN and malignant invasive cervical
      cancer. METHODS: Total number of PDT trial case was 50 cases and total number of
      patient was 22 patients who registered to PDT clinic. We used photogem sensitizer
      and 632 nm diode laser in early two cases. After then we performed PDT using
      photofrin sensitizer and 630 nm diode laser in other cases. We used flat-cut,
      microlens, cylindrical diffuser, and interstitial type optic fibers in order to
      irradiate the lesions. 240 J/cm2 energy was irradiated to the lesions. RESULTS:
      CIN 2 were 4 cases (18.2%) and CIN 3 were 15 (68.2%) and invasive cervical cancer
      were 3 (13.6%). Complete remission (CR) was found in 20 patients (91%). One case
      of 19 patients with CIN lesion recurred at 18 months after PDT treatment. CR was
      found in 18 cases in the patients with CIN lesions (95%). CR was found in 2 cases
      in the patients with invasive cervical cancer (67%). CONCLUSION: Our data showed
      that CR rate was fantastic in CIN group (95%). This study suggests that PDT can
      be recommended as new optimistic management modality on the patients with pre
      malignant CIN lesions including carcinoma in situ and relatively early invasive
      cancer of the uterine cervix. Combined chemo-photodynamic therapy is essential in
      case of invasive cervical cancer. For the young age group who desperately want to
      preserve their fertility and have a healthy baby, PDT can be a beacon of hope.

PMID- 27896248
TI  - Uterine artery pulsatility index in hypertensive pregnancies: When does the index
      normalize in the puerperium?
AB  - OBJECTIVE: To investigate whether the uterine artery pulsatility index (UtA PI)
      of hypertensive pregnancies is higher than that of normal pregnancies in the
      puerperium, as well as in the antepartum period. METHODS: The UtA PI was measured
      in hypertensive (group 1) and normal pregnancies (group 2) during antepartum,
      immediate postpartum or late postpartum periods. Using the transvaginal approach,
      the bilateral uterine artery indices were measured. RESULTS: One hundred twenty
      two women were enrolled: group 1, hypertensive disease in pregnancy (11 cases in
      antepartum, 13 cases in immediate postpartum and 10 cases in late postpartum
      period); group 2, normal pregnancies (32 cases in antepartum, 29 cases in
      immediate postpartum and 27 cases in late postpartum). In antepartum and
      immediate postpartum periods, the mean UtA PI and the proportion of cases with an
      early diastolic notch were higher in group 1 than in group 2 (antepartum mean UtA
      PI, 1.14 in group 1 vs. 0.68 in group 2, P<0.001; early diastolic notch, 46% vs.
      9%, P<0.05; immediate postpartum mean UtA PI, 1.30 vs. 1.08, P<0.05; early
      diastolic notch, 85% vs. 48%, P<0.05). In late postpartum period, the mean value
      of UtA PI of group 1 was still higher than that of group 2, although the
      proportion of cases with an early diastolic notch was not different (mean UtA PI,
      1.43 vs. 1.20, P<0.05; early diastolic notch, 60% vs. 52%, P=0.73). CONCLUSION:
      The UtA PI in hypertensive pregnancies was still higher than normal pregnancies
      in puerperal periods, suggesting that more than several weeks are required to
      resolve increased uterine artery vascular impedance.

PMID- 27896253
TI  - Study of dienogest for dysmenorrhea and pelvic pain associated with
      endometriosis.
AB  - OBJECTIVE: To evaluate the effect of orally administered dienogest (DNG) for
      dysmenorrhea and pelvic pain associated with endometriosis. METHODS: For this
      study we recruited 89 patients with dysmenorrhea and pelvic pain associated with
      endometriosis diagnosed by laparoscopy. All patients complained of persistent
      dysmenorrhea and pelvic pain despite surgical treatment 6 months previously.
      After 6 months of DNG treatment, we used a 0 to 3 point verbal rating scale to
      measure the severity of disability in daily life due to dysmenorrhea and pelvic
      pain, and the use of analgesics. Weight gain, serum lipid and liver enzyme tests
      were performed before treatment and after 6 months of DNG treatment. RESULTS:
      Total dysmenorrhea scores assessed by the verbal rating scale significantly
      decreased by the end of treatment (P<0.001). The mean (+/-standard deviation)
      pain score for dysmenorrhea before and after treatment were 1.42+/-1.1 and 0.1+/
      0.3, respectively. The mean non-menstrual pelvic pain scores before and after
      treatment were 0.52+/-0.6 and 0.18+/-0.3, respectively, showing a significant
      difference (P<0.001). The use of analgesics significantly decreased by the end of
      the treatment (P<0.001). The associated adverse effects were weight gains (in 56
      of 89 patients, 63%) and uterine bleeding (in 28 of 89 patients, 31.5%). The
      weight gain (before treatment, 57.9+/-9.7; after treatment, 61.1+/-12.6) was
      statistically significant (P<0.040). CONCLUSION: This study demonstrated that
      orally administered DNG could be used to effectively treat dysmenorrhea and
      pelvic pain associated with endometriosis although the side effects of weight
      gain and uterine bleeding should be considered.

PMID- 27896251
TI  - Combined SYBR Green real-time polymerase chain reaction and microarray method for
      the simultaneous determination of human papillomavirus loads and genotypes.
AB  - OBJECTIVE: The aim of this study was to describe the principle of the Cheil HPV
      DNA Chip assay and evaluate its accuracy. In order to quantify the human
      papillomavirus (HPV) load and identify HPV genotypes simultaneously, this assay
      combined the two methods: SYBR Green quantitative real-time polymerase chain
      reaction (PCR) and DNA microarray. METHODS: We designed novel consensus primer
      sets that target the conserved region of the HPV L1 gene for quantifying and
      detecting a broad range of HPV types by quantitative real-time PCR. Subsequently,
      using the PCR products, DNA microarray was performed with 36 HPV type-specific
      probes. To validate this method, direct sequencing and correlation analysis among
      HPV genotype, viral load, and cytological abnormality was performed by Cohen's
      kappa values, two-sided McNemar chi-square test, Kruskal-Wallis test, and odds
      ratios. RESULTS: The kappa value of the Cheil HPV DNA Chip was 0.963 (95%
      confidence interval, 0.919 to 0.98), which was significantly higher than the
      value of 0.527 (95% confidence interval, 0.447 to 0.59) obtained using a
      conventional HPV DNA Chip. HPV16 (chi2=62.28, P<0.01), HPV33 (chi2=7.18, P<0.01),
      and HPV58 (chi2=9.52, P<0.01), which are classified as high-risk HPVs, were
      detected at significant levels in samples with high-grade lesions. And viral
      loads tended to be higher in groups with high odds ratios. CONCLUSION: The Cheil
      HPV DNA Chip is an effective diagnostic assay for simultaneously detecting HPV
      genotypes and loads in cervical samples.

PMID- 27896252
TI  - Association between serum gonadotropin level and insulin resistance-related
      parameters in Korean women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the relationship between serum gonadotropin level and
      parameters related to insulin resistance in Korean women with polycystic ovary
      syndrome (PCOS). METHODS: This retrospective study included 138 women aged 18 to
      35 years who were newly diagnosed with PCOS according to the Rotterdam consensus.
      Participants were divided into three groups based on the serum luteinizing
      hormone to follicle-stimulating hormone (LH/FSH) ratio in the early follicular
      phase: group 1 (LH/FSH <1), group 2 (1.0<= LH/FSH >2.0), and group 3 (LH/FSH
      >=2.0). The correlations between the LH/FSH ratio and various metabolic
      parameters were evaluated using Pearson correlation coefficients. RESULTS:
      Patients with higher LH/FSH ratios showed higher total antral follicle counts and
      higher total ovarian volume. In the comparison of anthropometric and biochemical
      parameters among the three groups, the waist to hip ratio was the only parameter
      that differed significantly among the groups (P=0.003). Correlation analysis
      revealed no significant correlations between serum LH/FSH ratios and biochemical
      parameters related to insulin resistance. However, after adjustments for age and
      body mass index, a significant correlation between total cholesterol level and
      serum LH/FSH ratio was observed (r=0.221, P=0.018). CONCLUSION: Most parameters
      related to insulin resistance, with the exception of total cholesterol level, are
      unrelated to the inappropriate pattern of serum gonadotropin secretion in Korean
      women with PCOS.

PMID- 27896254
TI  - Laparoscopic tube-preserving surgical procedures for ectopic tubal pregnancy.
AB  - OBJECTIVE: To present our experience with laparoscopic tube-preserving surgery
      for ectopic tubal pregnancy and evaluate its feasibility and efficacy. METHODS:
      This was a prospective study of 57 consecutive patients with ectopic tubal
      pregnancies undergoing laparoscopic tube-preserving procedures including
      salpingotomy, salpingostomy, segmental resection and reanastomosis, and fimbrial
      milking. The outcome measures were treatment success rates and homolateral
      patency rates. RESULTS: Of the 57 surgical procedures, 55 (96.4%) were performed
      successfully without any additional intervention. The number of patients
      receiving salpingotomy, salpingostomy, segmental resection and reanastomosis, and
      fimbrial milking were 24 (42.1%), 25 (43.9%), 4 (7.0%), and 2 (3.5%),
      respectively. Two case was switched to salpingectomy because excessive bipolar
      coagulation was required to obtain hemostasis at the tubal bleeding bed. Over a
      mean beta-human chorionic gonadotropin resolution time of 18.3+/-5.9 days, no
      persistent trophoblast or postoperative complications occurred. A tubal patency
      test using hysterosalpingography was performed in 15 cases at 3 months
      postoperatively. Among these, the homolateral tubal patency rate was 75% (11 of
      15) and the contralateral patency rate was 80% (12 of 15). CONCLUSION: Tube
      preserving surgery is a feasible and safe treatment option for ectopic tubal
      pregnancy. However, considering that the optimal goal of tube-preserving surgical
      procedures is not the treatment success, some caution is warranted in
      interpreting results of this study.

PMID- 27896255
TI  - Recent trends in contraceptive use among Korean adolescents: Results from a
      nationwide survey from year 2013 to 2015.
AB  - OBJECTIVE: This study was aimed to evaluate the recent trends in contraceptive
      use among Korean adolescents. METHODS: Data reviewed were from the 2013-2015
      Korean Youth Risk Behavior Web-based Survey, which is a stratified, multistage
      sampling designed online-based research project performed annually by the Korean
      government to ensure a nationally representative sample of Korean adolescence.
      Eight questions related to the topic of contraception were reviewed for the
      outcome variables. RESULTS: A total of 212,538 adolescents attending middle
      school and high school participated in the survey, and 8,755 students among them
      who were sexually active were included in the study. The percentage of
      contraceptive use showed a steady increase from 39% in 2013 to 48.7% in 2015;
      however, the proportion of adolescents who have never used any kind of
      contraception still remains high. Highly effective methods such as oral
      contraceptives and intrauterine devices were used by only 10% to 15% of sexually
      active adolescents. CONCLUSION: The present study demonstrates the status of
      contraceptive use among Korean adolescents. Our data have the potential to help
      healthcare providers to formulate policies and develop interventions for
      encouraging effective contraceptive use among sexually active Korean adolescents.

PMID- 27896256
TI  - Comparative analysis of outcome between laparoscopic versus open surgical repair
      for vesico-vaginal fistula.
AB  - OBJECTIVE: Vesicovaginal fistula (VVF) causes detrimental psychosomatic effects
      on a woman. It is repaired using open abdominal as well as laparoscopic approach.
      Here we compare a series of open versus laparoscopic VVF repairs done at a single
      centre. METHODS: Retrospectively data of patients undergoing VVF repair in our
      department between January 2011 to December 2014 was analyzed. Patients who had a
      single, primary, simple VVF following a gynaecological surgery were included in
      the study. 26 patients met all the criteria. Out of these, thirteen patients had
      undergone a laparoscopic VVF repair (group 1) while thirteen had undergone an
      open transabdominal VVF repair (group 2). RESULTS: Mean fistula size was 2.14+/
      0.23 cm in group 1 and 2.18+/-0.30 cm in group 2, which was comparable. Mean
      blood loss was 58.69+/-6.48 mL in group 1 and 147.30+/-19.24 mL in group 2, which
      is statistically significant (P<0.0001). Mean hospital stay was 4 days in group 1
      and 13 days in group 2 which is statistically significant (P<0.0001). The
      analgesic requirement (diclofenac) was 261.53+/-29.95 mg in group 1 and 617.30+/
      34.43 mg in group 2, which is statistically significant (P<0.0001). Fistula
      repair was successful in all the patients in both the groups. CONCLUSION: The
      present study shows that laparoscopic VVF repair results in reduced patient
      morbidity and shorter hospital stay without compromising the results. So
      laparoscopic repair may be a more attractive treatment option for patients with
      post gynecology surgery VVF.

PMID- 27896257
TI  - A case of spontaneous hemoperitoneum by uterine vessel rupture in pregnancy.
AB  - A 27-year-old pregnant woman, para 1, was transferred to our hospital at 29+3
      weeks of gestation complaining of abdominal pain. She was diagnosed with
      hemoperitoneum based on ultrasonography. An emergency laparotomy was performed,
      and the bleeding was confirmed to be caused by ruptured surface blood vessels on
      the uterine fundus. Hemostasis with compression was successfully performed to
      sustain the pregnancy, and the patient delivered a full-term baby. Spontaneous
      hemoperitoneum during pregnancy caused by rupture of uterine blood vessels is
      very rare. It requires rapid diagnosis and surgical treatment because it
      increases the morbidity of the fetus and mother. In most incidences of
      spontaneous hemoperitoneum during pregnancy, a cesarean delivery is performed
      along with a simultaneous emergency laparotomy. However, in this case, the
      pregnancy was maintained to full term after surgical hemostasis, which prevented
      neonatal complications due to premature birth.

PMID- 27896258
TI  - Secondary abdominal pregnancy in human immunodeficiency virus-positive woman.
AB  - We report on an abdominal pregnancy in human immunodeficiency virus-positive
      mother, currently on antiretroviral therapy, which was discovered incidentally
      while training the obstetric ultrasound capacity building program. Although
      abdominal pregnancy is a rare form of ectopic pregnancy, it may be more common in
      women with HIV infection because they tend to have a higher rate of sexually
      transmitted diseases than the general population. The positive diagnosis of
      abdominal pregnancy is difficult to establish and is usually missed during
      prenatal assessment particularly in settings that lack routine ultrasound
      examination as is the case in most developing countries. For the management of
      abdominal pregnancy, surgical intervention is recommended and removal of the
      placenta is a key controversy. Ultrasonography is considered the front-line and
      most effective imaging method and an awareness with a high index of suspicion of
      abdominal pregnancy is vital for reducing associated high maternal and even
      higher perinatal mortality.

PMID- 27896259
TI  - Prenatal diagnosis of spontaneous twin anemia-polycythemia sequence and postnatal
      examination of placental vascular anastomoses.
AB  - Twin anemia-polycythemia sequence (TAPS) is characterized by a wide discrepancy
      of hemoglobin between two monochorionic fetuses without sign of twin oligo
      polyhydramnios sequence. A primiparous woman with monochorionic diamniotic twin
      transferred for preterm labor. Ultrasonographic evaluation at 32+3 weeks of
      gestation revealed increased middle cerebral artery-peak systolic velocity (77.4
      cm/sec, 1.69 multiples of median) in donor and decreased in recipient twin (36.4
      cm/sec, 0.79 multiples of median), the twin was diagnosed with TAPS. Repeated
      cesarean section was performed at 32+5 weeks of gestation following preeclampsia
      and preterm labor. After delivery, TAPS was confirmed through neonatal
      hematologic examination. There were no signs of acute hemorrhagic shock or brain
      injury. Placental evaluation via dye infusion and barium angiogram revealed one
      arterioarterial anastomoses with six arteriovenous anastomoses of placenta. We
      report a prenatally diagnosed case of spontaneous TAPS with arterioarterial and
      arteriovenous anastomoses and suggest careful monitoring of monochorionic twin
      and opinion on placenta vascular architecture.

PMID- 27896260
TI  - A case of prenatally diagnosed extrapulmonary arteriovenous malformation
      associated with a complex heart defect.
AB  - Pulmonary arteriovenous malformations are rare vascular anomalies of the lung,
      only a few cases of which have been diagnosed prenatally. The diagnostic clue for
      prenatal diagnosis was cardiomegaly with a particularly enlarged left atrium. All
      previous cases of pulmonary arteriovenous malformations diagnosed prenatally have
      been reported as an isolated anomaly or in association with simple heart defects.
      We here describe the first case of a pulmonary arteriovenous malformation with a
      complex heart defect that was diagnosed prenatally at 21.0 weeks of gestation and
      confirmed by postmortem autopsy.

PMID- 27896261
TI  - Giant invasive mole presenting as a cause of abdominopelvic mass in a
      perimenopausal woman: An unusual presentation of a rare pathology.
AB  - Invasive mole is a benign gestational trophoblastic disease that arises from the
      myometrial invasion of any gestational event via direct extension through tissue
      or vascular structures. Invasive mole (and other gestational trophoblastic
      diseases) may present with life-threatening complications including uterine
      perforation, excessive bleeding, acute hemoperitoneum, and abdominal pain. We
      report a case of invasive mole presenting as abdominal distention in a 51-year
      old perimenopausal woman (gravida 12, para 12, abortion 0). The patient was
      admitted to the gynecology clinic with a giant uterine mass filling the pelvic
      and abdominal cavity. To our knowledge, this is the first case in the literature
      of a gestational trophoblastic neoplasia presenting with uterine mass of 28
      weeks' gestational size in this age group. Interestingly, complications such as
      uterine rupture or invasion of the adjacent structures (such as parametrial
      tissues or blood vessels) had not developed in our patient despite the
      considerable enlargement of the uterus.

PMID- 27896262
TI  - Uterine arteriovenous malformation with positive serum beta-human chorionic
      gonadotropin: Embolization of both uterine arteries and extra-uterine feeding
      arteries.
AB  - The incidence of uterine arteriovenous malformation (AVM) is rare. However, it is
      clinically significant in that it can cause life-threatening vaginal bleeding. We
      report a case of a large uterine AVM with positive serum beta-human chorionic
      gonadotropin. A presumptive diagnosis was made; a uterine AVM accompanied by,
      early pregnancy or retained product of conception. Because this uterine AVM was
      extensive, transcatheter arterial embolization of both uterine arteries and extra
      uterine feeding arteries was performed. Three months after undergoing
      transcatheter arterial embolization, complete resolution of the uterine AVM was
      confirmed without major complication.

PMID- 27896263
TI  - Complete vaginal outlet stenosis in a patient with Sheehan's syndrome.
AB  - We present a case of complete vaginal stenosis in a woman diagnosed with
      Sheehan's syndrome. The patient delivered at full-term 5 months prior, and
      experienced massive postpartum bleeding at that time. During evaluation of
      persistent amenorrhea, we found that her vaginal orifice was completely adhesive
      and obstructed. Prior to corrective surgery, we managed the patient with an oral
      contraceptive to induce uterine bleeding into the vaginal outflow tract. After
      three cycles of an oral contraceptive, we could confirm that there was no
      stenotic lesion in the vaginal cavity as a hematocolpos was created. Adhesiolysis
      with scar revision for the vaginal stenosis was successfully performed; it was
      found that the lesion was limited to only the distal part of the vaginal outlet.
      Complete vaginal stenosis in reproductive age women with hypopituitarism has not
      been reported. The artificial induction of hematometrocolpos before surgery was
      useful in determining the extent of the stenotic lesion, and assured safety.

PMID- 27896264
TI  - Improving Fidelity of Translation of the Stepping On Falls Prevention Program
      through Root Cause Analysis.
AB  - BACKGROUND: Fidelity monitoring is essential with implementation of complex
      health interventions, but there is little description of how to use results of
      fidelity monitoring to improve the draft program package prior to widespread
      dissemination. Root cause analysis (RCA) provides a systematic approach to
      identifying underlying causes and devising solutions to prevent errors in complex
      processes. Its use has not been described in implementation science. METHODS:
      Stepping On (SO) is a small group, community-based intervention that has been
      shown to reduce falls by 31%. To prepare SO for widespread U.S. dissemination, we
      conducted a pilot of the draft program package, monitoring the seven SO sessions
      for fidelity of program delivery and assessing participant receipt and enactment
      through participant interviews after the workshop. Lapses to fidelity in program
      delivery, receipt, and enactment were identified. We performed a RCA to identify
      underlying causes of, and solutions to, such lapses, with the goal of preventing
      fidelity lapses with widespread dissemination. RESULTS: Lapses to fidelity in
      program delivery were in the domains of group leader's role, use of adult
      learning principles, and introducing and upgrading the exercises. Lapses in
      fidelity of participant receipt and enactment included lack of knowledge about
      balance exercises and reduced adherence to frequency of exercise practice and
      advancement of exercise. Root causes related to leader training and background,
      site characteristics and capacity, and participant frailty and expectations prior
      to starting the program. The RCA resulted in changes to the program manual, the
      training program, and training manual for new leaders, and to the methods for and
      criteria for participant and leader recruitment. A Site Implementation Guide was
      created to provide information to sites interested in the program. CONCLUSION:
      Disseminating complex interventions can be done more smoothly by first using a
      systematic quality improvement technique, such as the RCA, to identify how lapses
      in fidelity occur during the earliest stages of implementation. This technique
      can also help bring about solutions to these lapses of fidelity prior to
      widespread dissemination across multiple domain lapses.

PMID- 27896265
TI  - Social Mechanisms to Get People Outdoors: Bimodal Distribution of Interest in
      Nature?
AB  - We report results from a post-program survey (n = 930) of participants in a non
      profit outdoor health program targeted principally at women with families in
      Australia's metropolitan cities. We analyze communications, motivations,
      experiences, satisfaction, and intentions. The program involves 3 months' outdoor
      training in scenic locations, culminating in a single-day event. Training
      includes social opportunities and peer-group support. Event entry is in teams and
      includes charitable fundraising and personal challenges. Drop-out rates are very
      low, and repeat sign-up high. There are 2,000-3,600 places per event, and the
      most recent sold out in <24 h. We propose that for urban residents of developed
      nations, individual interest in exposure to nature may be bimodal rather than
      unimodal. Programs of this type target individuals most likely to shift from low
      interest to high-interest mode, using a set of social levers to change attitudes
      and behaviors. This contrasts with most public outdoor health programs, which
      assume a unimodal distribution and aim for small lifestyle changes at population
      scale. We suggest that the bimodal hypothesis is relevant to the sociocultural
      context of psychosocial interventions in a public health context, and merits
      direct testing.

PMID- 27896267
TI  - Editorial: Organ Fibrosis: Triggers, Pathways, and Cellular Plasticity.

PMID- 27896268
TI  - Challenges for Relative Effectiveness Assessment and Early Access of Cancer
      Immunotherapies in Europe.
AB  - Clinical endpoints relevant for relative effectiveness assessment (REA) reflect
      how patients feel, function, or survive. Outcome data requested by health
      technology assessment (HTA) bodies in Europe to support reimbursement of an
      anticancer drug are based on final endpoints coming from completed comparative
      phase 3 trials; overall survival improvement is the preferred criterion for the
      demonstration of the patient benefit in this field. Recent arrival of new
      treatments that target identified functional genetic mutations ("targeted
      therapies") or PD-1/PD-L1,2 axis ("immunotherapies") and their combinations have
      profoundly changed treatment strategies in cancers as they considerably improve
      patient survival, but also raise new challenges in REA and decision-making
      process in Europe as compared to the REA of "classical" chemotherapies. In
      addition, recent regulatory initiatives to support accelerated clinical
      development and approval of innovative cancer immunotherapies based on non-final
      endpoints, such as priority medicines through the European Medicines Agency,
      represent an additional challenge for HTA bodies and decision makers. In order to
      support adequate data generation for REA of anticancer drugs and especially for
      drugs candidates for accelerated assessment and early access to market, a close
      and open dialog of all stakeholders involved in development of such drugs is
      crucial.

PMID- 27896269
TI  - Cerebral Cavernous Malformations: Review of the Genetic and Protein-Protein
      Interactions Resulting in Disease Pathogenesis.
AB  - Mutations in the genes KRIT1, CCM2, and PDCD10 are known to result in the
      formation of cerebral cavernous malformations (CCMs). CCMs are intracranial
      lesions composed of aberrantly enlarged "cavernous" endothelial channels that can
      result in cerebral hemorrhage, seizures, and neurologic deficits. Although these
      genes have been known to be associated with CCMs since the 1990s, numerous
      discoveries have been made that better elucidate how they and their subsequent
      protein products are involved in CCM pathogenesis. Since our last review of the
      molecular genetics of CCM pathogenesis in 2012, breakthroughs include a more
      thorough understanding of the protein structures of the gene products,
      involvement with integrin proteins, and MEKK3 signaling pathways, and the
      importance of CCM2-PDCD10 interactions. In this review, we highlight the advances
      that further our understanding of the "gene to protein to disease" relationships
      of CCMs.

PMID- 27896266
TI  - In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation.
AB  - This review describes the role of bone cells and their surrounding matrix in
      maintaining bone strength through the process of bone remodeling. Subsequently,
      this work focusses on how bone formation is guided by mechanical forces and fluid
      shear stress in particular. It has been demonstrated that mechanical stimulation
      is an important regulator of bone metabolism. Shear stress generated by
      interstitial fluid flow in the lacunar-canalicular network influences maintenance
      and healing of bone tissue. Fluid flow is primarily caused by compressive loading
      of bone as a result of physical activity. Changes in loading, e.g., due to
      extended periods of bed rest or microgravity in space are associated with altered
      bone remodeling and formation in vivo. In vitro, it has been reported that bone
      cells respond to fluid shear stress by releasing osteogenic signaling factors,
      such as nitric oxide, and prostaglandins. This work focusses on the application
      of in vitro models to study the effects of fluid flow on bone cell signaling,
      collagen deposition, and matrix mineralization. Particular attention is given to
      in vitro set-ups, which allow long-term cell culture and the application of low
      fluid shear stress. In addition, this review explores what mechanisms influence
      the orientation of collagen fibers, which determine the anisotropic properties of
      bone. A better understanding of these mechanisms could facilitate the design of
      improved tissue-engineered bone implants or more effective bone disease models.

PMID- 27896270
TI  - The Assessment of Facial Expressions in Piglets Undergoing Tail Docking and
      Castration: Toward the Development of the Piglet Grimace Scale.
AB  - Many piglets are exposed to potentially painful husbandry procedures within the
      first week of life, including tail docking and castration, without the provision
      of either anesthesia or analgesia. The assessment methods used to evaluate pain
      experienced by piglets are often affected by low specificity and practical
      limitations, prompting the investigation of alternative methodologies. The
      assessment of changes in facial expression following a painful event has been
      successfully applied to several species. The objective of this pilot study was to
      evaluate the utility of a Grimace Scale applied to neonatal pigs to evaluate pain
      evoked by tail docking and castration. Eight female piglets, Sus scrofa
      domesticus (Landrace/Large White X synthetic sire line) underwent tail docking
      and 15 male piglets (75% Large White and 25% Belgian Landrace) were exposed to
      the castration procedure. Clear images of the faces of the piglets were collected
      immediately pre- and post-procedure. The images were used by experienced
      observers to identify facial action units (FAUs) which changed in individuals
      over this period, and a scoring scale was depicted in a training manual. A set of
      randomly selected images were then combined in a scorebook, which was evaluated
      after training by 30 scorers, blind to the treatment. The scale for most FAU was
      used with a high level of consistency across all observers. Tail docking induced
      a significant change (P < 0.05) in free moving piglets only in the "orbital
      tightening" FAU, whereas no change in any unit was observed in castrated piglets,
      which were restrained at the time of assessment. In this initial stage of
      development, orbital tightening seems to have the potential to be applied to
      investigate painful conditions in neonatal pigs. Nonetheless, more studies are
      needed to assess its full effectiveness and to evaluate the influence of possible
      confounds (e.g., handling stress) on the observed changes in FAUs.

PMID- 27896271
TI  - Expression and Clinical Significance of the Novel Long Noncoding RNA ZNF674-AS1
      in Human Hepatocellular Carcinoma.
AB  - Long noncoding RNAs (lncRNAs) play crucial roles in cancer occurrence and
      progression. However, the relationship between the expression levels of lncRNAs
      and the hepatocellular carcinoma (HCC) process is unclear. The goal of this study
      was to determine the expression level of ZNF674-AS1, a newly found lncRNA, in HCC
      and its clinical association. The expression of ZNF674-AS1 in 137 pairs of
      tumorous and adjacent normal tissues from patients with HCC was detected by
      quantitative real-time reverse transcription polymerase chain reaction.
      Additionally, the potential associations between its level in HCC tissue and
      clinicopathological features were analyzed. The expression of ZNF674-AS1 in the
      HCC cell lines HepG2, HCCLM3, SK-Hep1, HuH7, Hep3B, and MHCC97H was significantly
      downregulated compared with that in the normal liver cell line QSG-7701. The
      expression of ZNF674-AS1 was downregulated in 72% (99/137) of HCC tissues
      compared with that in paired adjacent normal tissues (p < 0.01). The results
      showed that the ZNF674-AS1 expression level was significantly correlated with
      metastasis (p = 0.041), clinical stage (p = 0.039), and histopathologic grading
      (p = 0.045). In addition, the Kaplan-Meier survival curves revealed that low
      ZNF674-AS1 expression was associated with poor prognosis in patients with HCC.
      Our data suggest that ZNF674-AS1 may play some role during cancer occurrence and
      progression and may be a new biomarker for HCC.

PMID- 27896272
TI  - Long Noncoding RNA-LET Suppresses Tumor Growth and EMT in Lung Adenocarcinoma.
AB  - Recently, many studies showed that long noncoding RNAs (lncRNAs) are involved in
      tumor progression. It is reported that lncRNA-LET is downregulated and has
      antitumor effect on several types of cancer. This study focuses on the role of
      lncRNA-LET on lung adenocarcinoma (LAC) progression. RT-PCR results indicated
      that frequent downregulation of lncRNA-LET in LAC tissues was related to
      clinicopathologic factors. lncRNA-LET knockdown significantly promoted LAC cell
      proliferation, invasion, and migration while lncRNA-LET overexpression obviously
      inhibited LAC cell proliferation, invasion, and migration, indicating a tumor
      inhibition of lncRNA-LET in LAC progression. Besides, lncRNA-LET inhibited EMT
      and negatively regulated Wnt/beta-catenin pathway in part. Our study suggests
      that lncRNA-LET exhibits an important tumor-suppressive effect on LAC progression
      by inhibiting EMT and Wnt/beta-catenin pathway, which provides potential
      therapeutic targets for LAC.

PMID- 27896273
TI  - Relationships between Muscle Architecture of Rectus Femoris and Functional
      Parameters of Knee Motion in Adults with Down Syndrome.
AB  - This study was designed to measure in vivo muscle architecture of the rectus
      femoris in adults with Down syndrome, testing possible relationships with
      functional parameters of the knee motion. Ten adults with Down syndrome and ten
      typically developed participated in the study. Pennation angle and thickness of
      the rectus femoris and subcutaneous layer of the thigh were measured via
      ultrasound imaging. Knee kinematics and electromyographic activity of the rectus
      femoris were recorded during free leg dropping. Muscle thickness was reduced and
      subcutaneous layer was thicker in persons with Down syndrome with respect to
      typically developed adults, but there were no differences in the pennation angle.
      The area of the rectus femoris EMG activity during the leg flexion was greater in
      Down syndrome with respect to typically developed adults. The leg movement
      velocity was lower in Down people than in controls, but the knee excursion was
      similar between the groups. Functional parameters correlated with pennation angle
      in the persons with Down syndrome and with muscle thickness in typically
      developed persons. The description of muscle architecture and the relationships
      between morphological and functional parameters may provide insights on the
      limits and the opportunities to overcome the inherent biomechanical instability
      in Down syndrome.

PMID- 27896274
TI  - Halo Gravity Traction Is Associated with Reduced Bone Mineral Density of Patients
      with Severe Kyphoscoliosis.
AB  - Background. Halo gravity traction (HGT) is one of the most commonly used
      perioperative techniques for the treatment of severe kyphoscoliosis. This study
      was to explore the influence of HGT on the BMD of these patients. Methods.
      Patients with severe kyphoscoliosis treated by preoperative HGT for at least 2
      months were included. Patients' BMD were assessed by dual-energy X-ray
      absorptiometry at lumbar spine (LS, L2-L4) and femur neck (FN) of the nondominant
      side. The weight and duration of traction, as well as baseline characteristics,
      were recorded. Results. Twenty patients were recruited. The average traction
      duration was 77.9 +/- 13.0 days while the mean traction weight was 39.9% +/-
      11.1% of total body weight. Remarkable decrease of BMD was observed at LS of 17
      (85%) patients and at FN of 18 (90%) patients. After HGT, 75% of patients were
      found to have osteoporosis, the incidence of which was significantly higher than
      that before HGT (35%). The correlation analysis revealed BMD reduction was only
      significantly correlated with the traction duration. Conclusions. The current
      study showed that preoperative HGT can have obvious impact on the BMD. The BMD
      reduction is associated with traction duration, suggesting that long traction
      duration may bring more bone mineral loss.

PMID- 27896275
TI  - Rationale for the Successful Management of EDTA Chelation Therapy in Human Burden
      by Toxic Metals.
AB  - Exposure to environmental and occupational toxicants is responsible for adverse
      effects on human health. Chelation therapy is the only procedure able to remove
      toxic metals from human organs and tissue, aiming to treat damage related to
      acute and/or chronic intoxication. The present review focuses on the most recent
      evidence of the successful use of the chelating agent ethylenediaminetetraacetic
      acid (EDTA). Assessment of toxic-metal presence in humans, as well as the
      rationale of EDTA therapy in cardiovascular and neurodegenerative diseases, is
      reported.

PMID- 27896276
TI  - The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential
      Treatment in Crohn's Disease: Experience from a Tertiary Medical Center in China.
AB  - Objective. To evaluate the efficacy of infliximab (IFX) monotherapy versus
      infliximab-azathioprine sequential treatment in Crohn's disease (CD) patients.
      Methods. Patients newly diagnosed with CD using IFX as induction therapy were
      enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy
      group and IFX-AZA sequential therapy group. Clinical remission rates were
      assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were
      assessed at weeks 84 and 138 to evaluate the efficacy of these two groups.
      Results. A total of seventy-nine patients had accomplished 138-week follow-up. At
      weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy
      group was significantly higher compared to IFX-AZA sequential therapy group
      (26/57 and 21/57) (P = 0.004 and 0.001, resp.). Similar findings were found in
      complete endoscopic remission rate. The clinical remission rates of IFX
      monotherapy group were similar to that of IFX-AZA sequential therapy group (P >
      0.05). At weeks 84 and 138, the endoscopic remission rate and the endoscopic
      improvement rate between these two groups displayed no significant difference (P
      > 0.05). Conclusion. IFX monotherapy provides higher deep remission rate compared
      with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who
      could not receive prolonged IFX therapy, IFX-AZA sequential therapy is
      acceptable, though long-term efficacy remains to be seen.

PMID- 27896278
TI  - Lack of Association between SLC30A8 Variants and Type 2 Diabetes in Mexican
      American Families.
AB  - SLC30A8 encodes zinc transporter 8 which is involved in packaging and release of
      insulin. Evidence for the association of SLC30A8 variants with type 2 diabetes
      (T2D) is inconclusive. We interrogated single nucleotide polymorphisms (SNPs)
      around SLC30A8 for association with T2D in high-risk, pedigreed individuals from
      extended Mexican American families. This study of 118 SNPs within 50 kb of the
      SLC30A8 locus tested the association with eight T2D-related traits at four
      levels: (i) each SNP using measured genotype approach (MGA); (ii) interaction of
      SNPs with age and sex; (iii) combinations of SNPs using Bayesian Quantitative
      Trait Nucleotide (BQTN) analyses; and (iv) entire gene locus using the gene
      burden test. Only one SNP (rs7817754) was significantly associated with incident
      T2D but a summary statistic based on all T2D-related traits identified 11 novel
      SNPs. Three SNPs and one SNP were weakly but interactively associated with age
      and sex, respectively. BQTN analyses could not demonstrate any informative
      combination of SNPs over MGA. Lastly, gene burden test results showed that at
      best the SLC30A8 locus could account for only 1-2% of the variability in T2D
      related traits. Our results indicate a lack of association of the SLC30A8 SNPs
      with T2D in Mexican American families.

PMID- 27896277
TI  - Prediction of Bacillus Calmette-Guerin Response in Patients with Bladder Cancer
      after Transurethral Resection of Bladder Tumor by Using Genetic Variation Based
      on Genomic Studies.
AB  - Purpose. We aimed to comprehensively review contemporary literature on genetic
      and epigenetic biomarkers associated with the prediction of Bacillus Calmette
      Guerin (BCG) response after the transurethral resection of a bladder tumor and to
      discuss the application of these biomarkers in precision cancer care for bladder
      cancer. Method. We performed a systematic review of published literatures in the
      databases PubMed and Embase by using the following key words: bladder cancer,
      BCG, gene, and methylation. Studies associated with cell lines, animal models,
      and muscle invasive bladder cancer were excluded. Results. The genetic variations
      associated with BCG response can be classified into three categories: germline
      variations, somatic variations, and epigenetic alterations. Genes related to BCG
      response were mainly involved in single-nucleotide polymorphisms, copy number
      variations, and gene methylations. Conclusions. Although these gene alterations
      are currently the most promising predictive markers of BCG response, most studies
      about bladder cancer DNA biomarkers are related to germline variations in
      candidate genes, and the results are not consistent. Only one study is related to
      somatic variation, and further evaluation in large-scale validation studies
      should be conducted to assess the potential clinical application of these
      findings. In addition, other biomarkers based on different "-omics" technologies
      should be considered in future studies.

PMID- 27896281
TI  - Genetics and genomic medicine in Morocco: the present hope can make the future
      bright.
AB  - Genetics and genomic medicine in Morocco: the present hope can make the future
      bright.

PMID- 27896279
TI  - A Case of Relapsing Polyarthritis Associated With Hidradenitis Suppurativa: Case
      Report and Review of Literature.
AB  - Hidradenitis suppurativa (HS) is a chronic, inflammatory follicular skin disease
      with recurrent skin nodules, sinus tracts, and scarring. We observed a case of HS
      associated with relapsing polyarthritis. On presentation the patient had a flare
      of polyarthritis with an increase in the number and size of pustular nodules. He
      has had similar episodes 1 to 2 times yearly subsiding with antibiotic treatment.
      Radiographs revealed erosions and demineralization. Symptoms improved following
      institution of anti-inflammatory and antibiotic therapy. HS is associated with
      several inflammatory conditions, and dysregulation in innate immunity may play an
      important role in etiopathogenesis. Spondyloarthritis/sacroiliitis is the most
      common joint manifestation in HS and mechanism(s) underlying arthropathy is
      unknown. Treatment of arthritis in HS is anecdotal.

PMID- 27896280
TI  - Genetic hearing loss: the journey of discovery to destination - how close are we
      to therapy?

PMID- 27896282
TI  - A patient with lissencephaly, developmental delay, and infantile spasms, due to
      de novo heterozygous mutation of KIF2A.
AB  - BACKGROUND: Microtubules are dynamic polymers of alpha/beta tubulin heterodimers
      that play a critical role in cerebral cortical development, by regulating
      neuronal migration, differentiation, and morphogenesis. Mutations in genes that
      encode either alpha- or beta-tubulin or a spectrum of proteins involved in the
      regulation of microtubule dynamics lead to clinically devastating malformations
      of cortical development, including lissencephaly. METHODS: This is a single case
      report or a patient with lissencephaly, developmental delay, nystagmus,
      persistent hyperplastic primary vitreous, and infantile spasms, and undertook a
      neurogenetic workup. We include studies of mutant function in Escherichia coli
      and HeLa cells. RESULTS: The patient was found to have a novel de novo mutation
      in kinesin family member 2A (KIF2A). This mutation results in a substitution of
      isoleucine at a highly conserved threonine residue within the ATP-binding domain.
      The KIF2A p.Thr320Ile mutant protein exhibited abnormal solubility, and KIF2A
      p.Thr320Ile overexpression in cultured cells led to the formation of aberrant
      microtubule networks. CONCLUSION: Findings support the pathogenic link between
      KIF2A mutation and lissencephaly, and expand the range of presentation to include
      infantile spasms and congenital anomalies.

PMID- 27896284
TI  - Analyses of more than 60,000 exomes questions the role of numerous genes
      previously associated with dilated cardiomyopathy.
AB  - BACKGROUND: Hundreds of genetic variants have been described as disease causing
      in dilated cardiomyopathy (DCM). Some of these associations are now being
      questioned. We aimed to identify the prevalence of previously DCM associated
      variants in the Exome Aggregation Consortium (ExAC), in order to identify
      potentially false-positive DCM variants. METHODS: Variants listed as DCM disease
      causing variants in the Human Gene Mutation Database were extracted from ExAC.
      Pathogenicity predictions for these variants were mined from dbNSFP v 2.9
      database. RESULTS: Of the 473 DCM variants listed in HGMD, 148 (31%) were found
      in ExAC. The expected number of individuals with DCM in ExAC is 25 based on the
      prevalence in the general population. Yet, 35 variants were found in more than 25
      individuals. In 13 genes, we identified all variants previously associated with
      DCM; four genes contained variants above our estimated cut-off. Prediction tools
      found ExAC variants to be significantly more tolerated when compared to variants
      not found in ExAC (P = 0.004). CONCLUSION: In ExAC, we identified a higher
      genotype prevalence of variants considered disease-causing than expected. More
      importantly, we found 13 genes in which all variants previously associated with
      DCM were identified in ExAC, questioning the association of these genes with the
      monogenic form of DCM.

PMID- 27896283
TI  - A potential founder variant in CARMIL2/RLTPR in three Norwegian families with
      warts, molluscum contagiosum, and T-cell dysfunction.
AB  - BACKGROUND: Four patients from three Norwegian families presented with a common
      skin phenotype of warts, molluscum contagiosum, and dermatitis since early
      childhood, and various other immunological features. Warts are a common
      manifestation of human papilloma virus (HPV), but when they are overwhelming,
      disseminated and/or persistent, and presenting together with other immunological
      features, a primary immunodeficiency disease (PIDD) may be suspected. METHODS AND
      RESULTS: The four patients were exome sequenced as part of a larger study for
      detecting genetic causes of primary immunodeficiencies. No disease-causing
      variants were identified in known primary immunodeficiency genes or in other
      disease-related OMIM genes. However, the same homozygous missense variant in
      CARMIL2 (also known as RLTPR) was identified in all four patients. In each
      family, the variant was located within a narrow region of homozygosity,
      representing a potential region of autozygosity. CARMIL2 is a protein of
      undetermined function. A role in T-cell activation has been suggested and the
      mouse protein homolog (Rltpr) is essential for costimulation of T-cell activation
      via CD28, and for the development of regulatory T cells. Immunophenotyping
      demonstrated reduced regulatory, CD4+ memory, and CD4+ follicular T cells in all
      four patients. In addition, they all seem to have a deficiency in IFN gamma 
      synthesis in CD4+ T cells and NK cells. CONCLUSIONS: We report a novel primary
      immunodeficiency, and a differential molecular diagnosis to CXCR4-,DOCK8-,GATA2
      ,MAGT1-,MCM4-,STK4-,RHOH-,TMC6-, and TMC8-related diseases. The specific variant
      may represent a Norwegian founder variant segregating on a population-specific
      haplotype.

PMID- 27896285
TI  - Rare variants in optic disc area gene CARD10 enriched in primary open-angle
      glaucoma.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified association of
      common alleles with primary open-angle glaucoma (POAG) and its quantitative
      endophenotypes near numerous genes. This study aims to determine whether rare
      pathogenic variants in these disease-associated genes contribute to POAG.
      METHODS: Participants fulfilled strict inclusion criteria of advanced POAG at a
      young age of diagnosis. Myocilin mutation carriers were excluded using direct
      sequencing. Whole exome sequencing was performed on 187 glaucoma cases and 103
      local screened nonglaucoma controls then joint-called with exomes of 993
      previously sequenced Australian controls. GWAS-associated genes were assessed for
      enrichment of rare predicted pathogenic variants in POAG. Significantly enriched
      genes were compared against Exome Aggregation Consortium (ExAC) public control.
      RESULTS: Eighty-six GWAS disease or trait-associated glaucoma genes were captured
      and sequenced. CARD10 showed enrichment after Bonferroni correction for rare
      variants in glaucoma cases (OR = 13.2, P = 6.94 * 10-5) with mutations identified
      in 4.28% of our POAG cohort compared to 0.27% in controls. CARD10 was
      significantly associated with optic disc parameters in previous GWAS. The whole
      GWAS gene set showed no enrichment in POAG overall (OR = 1.12, P = 0.51).
      CONCLUSION: We report here an enrichment of rare predicted pathogenic coding
      variants within a GWAS-associated locus in POAG (CARD10). These findings indicate
      that both common and rare pathogenic coding variants in CARD10 may contribute to
      POAG pathogenesis.

PMID- 27896286
TI  - Aneuploidy screening using circulating fetal cells in maternal blood by dual
      probe FISH protocol: a prospective feasibility study on a series of 172 pregnant
      women.
AB  - BACKGROUND: A long sought goal in medical genetics has been the replacement of
      invasive procedures for the detection of chromosomal aneuploidies by isolating
      and analyzing fetal cells or free fetal DNA from maternal blood, avoiding risk to
      the fetus. However, a rapid, simple, consistent, and low-cost procedure suitable
      for routine clinical practice has not yet been achieved. The purpose of this
      study was to assess the feasibility of predicting fetal aneuploidy by applying
      our recently established dual-probe FISH protocol to fetal cells isolated and
      enriched from maternal blood. METHODS: A total of 172 pregnant women underwent
      prospective testing for fetal aneuploidy by FISH analysis of fetal cells isolated
      from maternal blood. Results were compared with the karyotype determined through
      invasive procedures or at birth. RESULTS: Seven of the samples exhibited fetal
      aneuploidy, which was confirmed by invasive prenatal diagnosis procedures. After
      enrichment for fetal cells, the frequency of trisomic cells was at least double
      in samples from aneuploid pregnancies (range 0.38-0.90%) compared to samples from
      normal pregnancies (<=0.18%). One false negative result was also obtained.
      CONCLUSIONS: Noninvasive prenatal aneuploidy screening using fetal cells isolated
      from maternal blood is feasible and could substantially reduce the need for
      invasive procedures.

PMID- 27896287
TI  - Enamel ribbons, surface nodules, and octacalcium phosphate in C57BL/6 Amelx-/-
      mice and Amelx+/- lyonization.
AB  - BACKGROUND: Amelogenin is required for normal enamel formation and is the most
      abundant protein in developing enamel. METHODS: Amelx+/+, Amelx+/- , and Amelx-/-
      molars and incisors from C57BL/6 mice were characterized using RT-PCR, Western
      blotting, dissecting and light microscopy, immunohistochemistry (IHC),
      transmission electron microscopy (TEM), scanning electron microscopy (SEM),
      backscattered SEM (bSEM), nanohardness testing, and X-ray diffraction. RESULTS:
      No amelogenin protein was detected by Western blot analyses of enamel extracts
      from Amelx-/- mice. Amelx-/- incisor enamel averaged 20.3 +/- 3.3 MUm in
      thickness, or only 1/6th that of the wild type (122.3 +/- 7.9 MUm). Amelx-/-
      incisor enamel nanohardness was 1.6 Gpa, less than half that of wild-type enamel
      (3.6 Gpa). Amelx+/- incisors and molars showed vertical banding patterns unique
      to each tooth. IHC detected no amelogenin in Amelx-/- enamel and varied levels of
      amelogenin in Amelx+/- incisors, which correlated positively with enamel
      thickness, strongly supporting lyonization as the cause of the variations in
      enamel thickness. TEM analyses showed characteristic mineral ribbons in Amelx+/+
      and Amelx-/- enamel extending from mineralized dentin collagen to the ameloblast.
      The Amelx-/- enamel ribbons were not well separated by matrix and appeared to
      fuse together, forming plates. X-ray diffraction determined that the predominant
      mineral in Amelx-/- enamel is octacalcium phosphate (not calcium hydroxyapatite).
      Amelx-/- ameloblasts were similar to wild-type ameloblasts except no Tomes'
      processes extended into the thin enamel. Amelx-/- and Amelx+/- molars both showed
      calcified nodules on their occlusal surfaces. Histology of D5 and D11 developing
      molars showed nodules forming during the maturation stage. CONCLUSION: Amelogenin
      forms a resorbable matrix that separates and supports, but does not shape early
      secretory-stage enamel ribbons. Amelogenin may facilitate the conversion of
      enamel ribbons into hydroxyapatite by inhibiting the formation of octacalcium
      phosphate. Amelogenin is necessary for thickening the enamel layer, which helps
      maintain ribbon organization and development and maintenance of the Tomes'
      process.

PMID- 27896288
TI  - Ultrastructure of early amelogenesis in wild-type, Amelx-/-, and Enam-/- mice:
      enamel ribbon initiation on dentin mineral and ribbon orientation by ameloblasts.
AB  - INTRODUCTION: Dental enamel is comprised of highly organized, oriented apatite
      crystals, but how they form is unclear. METHODS: We used focused ion beam (FIB)
      scanning electron microscopy (SEM) to investigate early enamel formation in 7
      week-old incisors from wild-type, Amelx-/-, and Enam-/- C56BL/6 mice. FIB surface
      imaging scans thicker samples so that the thin enamel ribbons do not pass as
      readily out of the plane of section, and generates serial images by a mill and
      view approach for computerized tomography. RESULTS: We demonstrate that wild-type
      enamel ribbons initiate on dentin mineral on the sides and tips of mineralized
      collagen fibers, and extend in clusters from dentin to the ameloblast membrane.
      The clustering suggested that groups of enamel ribbons were initiated and then
      extended by finger-like membrane processes as they retracted back into the
      ameloblast distal membrane. These findings support the conclusions that no
      organic nucleator is necessary for enamel ribbon initiation (although no ribbons
      form in the Enam-/- mice), and that enamel ribbons elongate along the ameloblast
      membrane and orient in the direction of its retrograde movement. Tomographic
      reconstruction videos revealed a complex of ameloblast membrane processes and
      invaginations associated with intercellular junctions proximal to the
      mineralization front and also highlighted interproximal extracellular enamel
      matrix accumulations proximal to the interrod growth sites, which we propose are
      important for expanding the interrod matrix and extending interrod enamel
      ribbons. Amelx-/- mice produce oriented enamel ribbons, but the ribbons fuse into
      fan-like structures. The matrix does not expand sufficiently to support formation
      of the Tomes process or establish rod and interrod organization. CONCLUSION:
      Amelogenin does not directly nucleate, shape, or orient enamel ribbons, but
      separates and supports the enamel ribbons, and expands the enamel matrix to
      accommodate continued ribbon elongation, retrograde ameloblast movement, and
      rod/interrod organization.

PMID- 27896291
TI  - Fresh Osteochondral Allograft to the Humeral Head for Treatment of an Engaging
      Reverse Hill-Sachs Lesion: Technical Case Report and Literature Review.

PMID- 27896290
TI  - Do Clinical Results and Return-to-Sport Rates After Ulnar Collateral Ligament
      Reconstruction Differ Based on Graft Choice and Surgical Technique?
AB  - BACKGROUND: Ulnar collateral ligament reconstruction (UCLR) has become a common
      procedure performed in overhead-throwing athletes of many athletic levels.
      PURPOSE/HYPOTHESIS: The purpose of this study was to determine whether clinical
      outcomes and return-to-sport (RTS) rates differ among patients undergoing UCLR
      based on graft choice, surgical technique, athletic competition level,
      handedness, and treatment of the ulnar nerve. We hypothesized that no differences
      would exist in clinical outcomes or RTS rates between technique, graft choice, or
      other variables. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All
      patients who underwent UCLR from January 1, 2004 through December 31, 2014 at a
      single institution were identified. Charts were reviewed to determine patient
      age, sex, date of surgery, sport played, handedness, athletic level, surgical
      technique, graft type, and complications. Patients were contacted via telephone
      to obtain the RTS rate, Conway-Jobe score, Timmerman-Andrews score, and Kerlan
      Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow score. RESULTS: Eighty-five
      patients (mean age at surgery, 19.3 +/- 4.7 years; 92% male; 78% right hand
      dominant) underwent UCLR between 2004 and 2014 and were available for follow-up.
      Overall, 87% were baseball pitchers, 49.4% were college athletes, and 41.2% were
      high school athletes. No significant difference existed between the docking and
      double-docking techniques, graft choice, handedness, sex, activity level, and
      treatment of the ulnar nerve with regard to clinical outcomes, RTS, or subsequent
      surgeries (all P > .05). More complications were seen in the docking technique
      compared with the double-docking technique (P = .036). Hamstring autograft was
      used more commonly with the docking technique (P = .023) while allograft was used
      more commonly with the double-docking technique (P = .0006). CONCLUSION: Both the
      docking and double-docking techniques produce excellent clinical outcomes in
      patients undergoing UCLR. No difference in outcome scores was seen between
      surgical technique or graft type. The double-docking technique had fewer
      complications than the docking technique.

PMID- 27896289
TI  - How, who, and when: preferences for delivery of genome sequencing results among
      women diagnosed with breast cancer at a young age.
AB  - BACKGROUND: The increasing use of genome sequencing with patients raises a
      critical communication challenge: return of secondary findings. While the issue
      of what sequencing results should be returned to patients has been examined, much
      less attention has been paid to developing strategies to return these results in
      ways that meet patients' needs and preferences. To address this, we investigated
      delivery preferences (i.e., who, how, when) for individual genome sequencing
      results among women diagnosed with breast cancer at age 40 or younger. METHODS:
      We conducted 60 semistructured, in-person individual interviews to examine
      preferences for the return of different types of genome sequencing results and
      the reasons underlying these preferences. Two coders independently coded
      interview transcripts; analysis was conducted using NVivo 10. RESULTS: The major
      findings from the study were that: (1) many participants wanted sequencing
      results as soon as possible, even at the time of breast cancer diagnosis; (2)
      participants wanted an opportunity for an in-person discussion of results; and
      (3) they put less emphasis on the type of person delivering results than on the
      knowledge and communicative skills of that person. Participants also emphasized
      the importance of a results return process tailored to a patient's individual
      circumstances and one that she has a voice in determining. CONCLUSIONS: A
      critical goal for future transdisciplinary research including clinicians,
      patients, and communication researchers may be to develop decision-making
      processes to help patients make decisions about how they would like various
      sequencing results returned.

PMID- 27896292
TI  - Shoulder Arthroplasty Outcomes in Patients With Multiple Reported Drug Allergies:
      Does Number of Drug Allergies Have an Effect on Outcome?
AB  - BACKGROUND: The presence of multiple allergies has been correlated with worse
      outcomes for patients undergoing hip and knee arthroplasty, but the effect of
      allergies has not yet been elucidated with respect to shoulder arthroplasty.
      PURPOSE/HYPOTHESIS: The purpose of this study is to identify any discrepancies in
      shoulder arthroplasty outcomes with respect to reported drug allergies. We
      hypothesized that patients with multiple drug allergies would have inferior
      outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included in
      the analysis were a single surgeon's cases between 2009 and 2014 of primary total
      shoulder arthroplasty with a minimum of 180 days of follow-up. Cases with
      fracture as the indication were excluded. Preoperative and postoperative metrics
      included visual analog scale (VAS) for pain, forward flexion range of motion, and
      Simple Shoulder Test (SST) results, and postoperative patient satisfaction scores
      were also collected. Chi-square and 1-way analysis of variance with Tukey post
      hoc analyses were performed when appropriate. RESULTS: A total of 98 patients
      were included (no allergies, n = 51; single allergy, n = 21; multiple allergies,
      n = 26). The proportion of females was greater with increasing number of
      allergies (no allergies, 31%; single allergies, 47%; multiple allergies, 88%;
      Pearson chi2 = 22.5; P < .0001). Both preoperatively and postoperatively, no
      difference was found between cohorts with respect to SST score, VAS score, or
      forward flexion. There was also no difference in postoperative satisfaction
      between cohorts. No difference between cohorts was identified when comparing the
      pre- to postoperative change in SST scores, VAS scores, or forward flexion.
      CONCLUSION: The presence of single or multiple allergies is not correlated with
      worse outcomes after primary anatomic total shoulder arthroplasty.

PMID- 27896293
TI  - Yoga-Related Injuries in the United States From 2001 to 2014.
AB  - BACKGROUND: Yoga has become more popular among people in the United States and
      has been touted by both yoga participants as well as some physicians and
      researchers for its health benefits. While the health benefits have been studied,
      the frequency of injury among yoga participants has not been well documented.
      PURPOSE: Injury incidence, rates, and types associated with yoga in the United
      States have not been quantified. This study estimates US yoga-associated injury
      incidence and characterizes injury type over a 13-year period. STUDY DESIGN:
      Descriptive epidemiology study. METHODS: Data from the National Electronic Injury
      Surveillance System (NEISS) from 2001 to 2014 were used to estimate the incidence
      and type of yoga-associated injuries. The number and age distribution of yoga
      participants was estimated using data from National Health Statistics Reports.
      These national population estimates were applied to the NEISS data to determine
      injury rates overall and stratified according to age categories. RESULTS: There
      were 29,590 yoga-related injuries seen in hospital emergency departments from
      2001 to 2014. The trunk (46.6%) was the most frequent region injured, and
      sprain/strain (45.0%) accounted for the majority of diagnoses. The injury rate
      increased overall from 2001 to 2014, and it was greatest for those aged 65 years
      and older (57.9/100,000) compared with those aged 18 to 44 years (11.9/100,000)
      and 45 to 64 years (17.7/100,000) in 2014. CONCLUSION: Participants aged 65 years
      and older have a greater rate of injury from practicing yoga when compared with
      other age groups. Most injuries sustained were to the trunk and involved a
      sprain/strain. While there are many health benefits to practicing yoga,
      participants and those wishing to become participants should confer with a
      physician prior to engaging in physical activity and practice only under the
      guidance of certified instructors.

PMID- 27896295
TI  - Retraction of: Violence and Gender, 2016;3(2):100-106; DOI:
      10.1089/vio.2016.0003.
AB  - [This retracts the article on p. 100 in vol. 3.].

PMID- 27896296
TI  - Eradication of Mycobacterium abscessus Pulmonary Infection in a Child With
      Idiopathic Bronchiectasis.

PMID- 27896294
TI  - A Qualitative Assessment of Return to Sport After Hip Arthroscopy for
      Femoroacetabular Impingement.
AB  - BACKGROUND: Hip arthroscopy for femoroacetabular impingement (FAI) is known to
      produce excellent outcomes, yet some patients do not return to their preinjury
      level of sport participation. Much literature on return to sport has revolved
      around anterior cruciate ligament reconstruction and even shoulder instability,
      but none to date have used qualitative, semistructured patient interviews on
      patients with hip labral tears. PURPOSE: To understand the factors influencing
      the decision to return to sport after arthroscopic hip surgery for FAI. STUDY
      DESIGN: Case series; Level of evidence, 4. METHODS: An experienced interviewer
      conducted qualitative, semistructured interviews of patients aged 18 to 60 years
      who had arthroscopic hip surgery for FAI. All had preinjury participation in
      sport and a minimum 2-year follow-up with no revision surgery. Qualitative
      analysis was then performed to derive codes, categories, and themes. An
      assessment of preinjury and current sports participation by type, level of
      competition, and frequency along with patient-reported hip function was also
      obtained. In addition, current modified Harris Hip Score (mHHS), international
      Hip Outcome Tool (iHOT-12), Hip Outcome Score-sports-specific subscale (HOS-SSS),
      and a coping mechanism evaluation (Brief COPE) were also recorded. RESULTS: A
      total of 23 patients were interviewed to reveal the overarching themes of
      internal motivation, external encouragement, and resetting expectations as the
      predominant factors influencing a patient's decision to return to preinjury
      sport. Subjective outcome measurements (mHHS, iHOT-12, patient satisfaction)
      showed significant differences between patients who did and did not return to
      sport. Interestingly, the adaptive and maladaptive coping mechanisms matched and
      supported our themes in those patients who described fear and self-motivation as
      defining features influencing their cessation of or return to play, respectively.
      CONCLUSION: Self-motivation, aging, pain, encouragement from others, and adapting
      to physical limitations can largely affect a patient's decision to return to
      sport after arthroscopic hip surgery for FAI. Innate coping mechanisms may also
      help to predict the course of and subsequently aid in a patient's postoperative
      recovery.

PMID- 27896297
TI  - A Mouse Model of Multi-Drug Resistant Staphylococcus aureus-induced Ocular
      Disease.
AB  - Staphylococcus aureus infection of the cornea is a significant threat to vision.
      The percentage of bacterial isolates resistant to antibiotics is increasing as is
      the percentage of infections caused by methicillin resistant isolates. There is a
      critical need for additional therapeutic approaches and their development will
      require the use of animal models to test efficacy. Two mouse models of S. aureus
      keratitis have been described but only quantified stromal keratitis (corneal
      clouding and perforation). We have extended these models using the methicillin
      resistant S. aureus USA300 LAC strain and show that eyelid inflammation and
      swelling (blepharitis) and corneal neovascularization can be quantified. This
      expanded model should prove useful in assessing additional effects of
      antibacterial therapies and additional pathological mechanisms involved in
      bacterial ocular infection.

PMID- 27896298
TI  - Applying latent class assignments for accelerometry data to external populations:
      Data from the National Health and Nutrition Examination Survey 2003-2006.
AB  - Latent class analysis can identify unmeasured mutually exclusive categories
      (class membership) among participants for either observed categorical or
      continuous variables. More recently, latent class analysis has been applied to
      accelerometry to better understand the day-to-day patterns of physical activity
      and sedentary behavior. Typically, the class assignments are only relevant to the
      study for which they were derived and not made available for others to use. Using
      one-week accelerometry (ActiGraph #AM7164) data collected from the National
      Health and Nutrition Examination Survey during 2003-2006, latent classes of
      physical activity and sedentary behavior were derived separately for youths 6-17
      years and adults >=18 years. The purpose of this article is to provide the latent
      class assignments developed on this source population (United States) available
      to others to apply to their studies using similarly collected accelerometry. This
      method will extend the usefulness of the latent class analysis and allow for
      comparisons across studies.

PMID- 27896300
TI  - Data from a survey to determine visitor attitudes and knowledge about the
      provisioning of wild dolphins at a marine tourism destination.
AB  - In the Austral summer of 2014-2015 we surveyed visitors at the popular marine
      tourism destination of Koombana Bay, Bunbury, Western Australia to investigate
      resident and visitor attitudes towards the provisioning of the wild dolphins and
      their knowledge about the legal, social and environmental repercussions arising
      from the unregulated provisioning of the dolphins. We report the data collected
      in our survey along with our preliminary statistical analyses and the survey
      instrument we utilized to collect the data.

PMID- 27896299
TI  - Basement membrane ultrastructure and component localization data from uterine
      tissues during early mouse pregnancy.
AB  - Basement membranes (BMs) are specialized extracellular scaffolds that provide
      architecture and modulate cell behaviors in tissues, such as fat, muscle,
      endothelium, endometrium, and decidua. Properties of BMs are maintained in
      homeostasis for most adult tissues. However, BM ultrastructure, composition, and
      localization are rapidly altered in select uterine tissues that are reprogrammed
      during pregnancy to enable early maternal-embryo interactions. Here, our data
      exhibit both static and dynamic BMs that were tracked in mouse uterine tissues
      during pre-, peri-, and postimplantation periods of pregnancy. The data exhibit
      spatial-temporal patterns of BM property regulation that coincide with the
      progression of adapted physiology. Further interpretation and discussion of these
      data in this article are described in the associated research article titled,
      "Embryo implantation triggers dynamic spatiotemporal expression of the basement
      membrane toolkit during uterine reprogramming" (C.R. Jones-Paris, S. Paria, T.
      Berg, J. Saus, G. Bhave, B.C. Paria, B.G. Hudson, 2016) [1].

PMID- 27896301
TI  - Data set for describing the elaboration of a compatible Gateway-based co
      expression vector set and supporting its validation.
AB  - This article contains Supplementary Data including methods and figures that
      relate to the article entitled "Construction of a compatible Gateway-based co
      expression vector set for expressing multiprotein complexes in E. coli" (L.
      Salim, C. Feger, D. Busso, 2016) [1] that describes the elaboration and the
      validation of a set of versatile compatible plasmids for co-expression studies in
      Escherichia coli. Here, we describe experimental procedures for plasmid
      construction and recombinant protein expression. We give the list of the 33 (co)
      expression plasmids encoding fluorescent protein and we show extensive
      experimental data obtained for all combinations tested for validating our vector
      set.

PMID- 27896302
TI  - Data on the uptake and metabolism of the vertebrate steroid estradiol-17beta from
      water by the common mussel, Mytilus spp.
AB  - The data presented in this article primarily provide support for the research
      article entitled "Mussels (Mytilus spp.) display an ability for rapid and high
      capacity uptake of the vertebrate steroid, estradiol-17beta from water" (T.I.
      Schwarz, I. Katsiadaki, B.H. Maskrey, A.P. Scott, 2016) [1]. Data are presented
      on the ability of mussels to absorb tritiated estradiol (E2) from water. The data
      indicate that most of the radioactivity remaining in the water is 1,3,5(10)
      estratriene-3,17beta-diol 3-sulfate (E2 3-S) and the radioactivity in the mussel
      tissue is mainly in the form of fatty acid esters. The latter, following
      saponification, were identified by ultra-high performance liquid chromatography
      in conjunction with tandem mass spectrometry (UHPLC-MS/MS) as intact E2. Data are
      included that indicate that the remaining radioactivity in the tissue is composed
      of E2 3-S and unidentified free metabolites. Experimental data included also
      relate to a) the efficiency of extraction of radioactivity from tissue, b) the
      efficiency of separation of free and esterified E2 using solvents and c) possible
      factors affecting the recovery of radioactivity. Finally, preliminary data are
      provided on concentrations of immunoreactive E2 in the free and ester fractions
      of tissue extracts from mussels caged in the field.

PMID- 27896303
TI  - Data on some socio-economic parameters explaining the movement of extra-EU asylum
      seekers in Europe.
AB  - This article contains data concerning the movement of extra-EU asylum seekers in
      Europe. Data used in this paper were collected from the Eurostat database and the
      UNHCR database. The data consist of some socio-economic features related to 30
      European countries where extra-EU asylum seekers have applied for protection. All
      variables were transformed into their natural logs. The degree of statistical
      correlation is evaluated from Pearson's coefficient, using the 0.05 level of
      significance. Regression analysis is conducted to identify some socio-economic
      predictors of countries attracting asylum migration. Six models are presented,
      where 'first time asylum applicants' in 2015 (1,324,215 individuals) in 30
      European countries were regressed on 2014 predictors. The multilinear regression
      model was tested by using data on asylum seekers in 2014, regressed on the same
      predictors referred to 2013. The data here shared provide a resource for
      researchers working in the topical field of migration.

PMID- 27896304
TI  - Utilization of zinc chloride for surface modification of activated carbon derived
      from Jatropha curcas L. for absorbent material.
AB  - The objective of this research is to produce the low-cost activated carbon from
      Jatropha curcas L. by chemical activation using zinc chloride ZnCl2. The effects
      of the impregnation ratio on the surface and chemical properties of activated
      carbon were investigated. The impregnation ratio was selected at the range of 1:1
      10:1 for investigation. The optimum conditions resulted in an activated carbon
      with a carbon content of 80% wt, while the specific surface area evaluated using
      nitrogen adsorption isotherm corresponds to 600 m2/g.

PMID- 27896305
TI  - Measuring resilience to financial instability: A new dataset.
AB  - In recognition of the severe consequences of the recent international financial
      crisis, the topic of macroprudential policy has elicited considerable research
      effort. The data set reports, for 46 economies around the globe, an index of the
      capacity to deploy macroprudential policies. The index aims to represent the
      essence of what constitutes a macroprudential regime is developed and used in
      http://dx.doi.org/10.1016/j.jfs.2016.08.007 (D. Lombardi, P.L. Siklos, 2016) [1].
      Specifically, the index quantifies: (1) how existing macroprudential frameworks
      are organized; and (2) how far a particular jurisdiction is from reaching the
      goals established by the Group of Twenty (G20) and the Financial Stability Board
      (FSB). The latter is a benchmark that has not been considered in the burgeoning
      literature that seeks to quantify the role of macroprudential policies.

PMID- 27896306
TI  - Data for increased Rho kinase activity in type 2 diabetic patients.
AB  - The data presented in this article are related to the research article entitled
      "Enhanced Rho-Kinase Activity: Pathophysiological Relevance in Type 2 Diabetes"
      [1]. Rho-Kinase has attracted a great deal of interest as a novel therapeutic
      target in cardiovascular diseases. These data describe the observed relationship
      of Rho-Kinase activity with type 2 diabetic patients. Rho-Kinase activity is
      determined by immunoblotting of peripheral blood leukocytes with the Phospho
      Thr853 in the myosin-binding subunit of myosin light-chain phosphatase. The level
      of IL-6 is measured using Enzyme-linked immunosorbent assay.

PMID- 27896307
TI  - Data on birds and habitat associated with forest management on public
      conservation areas in the Mississippi Alluvial Valley.
AB  - This data article contains data collected from 2006-2012 in forests located on 31
      State or Federal conservation lands in or adjacent to the Mississippi Alluvial
      Valley. We present the location, treatment type, and silvicultural age of data
      collection locations. Presented data on bird detections and forest habitat were
      collected during avian point counts and associated forest habitat plots and
      linked to the publication (D.J. Twedt and R.R. Wilson, 2017) [5].

PMID- 27896308
TI  - Small cell ovarian carcinoma: Long term survival in juvenile case with poor
      prognostic features.
AB  - BACKGROUND: Ovarian small cell carcinoma is a rare, aggressive neoplasm that
      occurs in young women and has a poor long-term prognosis. Treatment involves
      surgical resection and chemotherapy. The required radicality of surgery is
      uncertain, balancing cytoreduction with fertility preservation. Various
      chemotherapy regimens are utilized due to confusion regarding the neoplasm's
      lineage. Case We describe an adolescent with small cell carcinoma, hypercalcemic
      type, stage IA. Surgery included left salpingo-oopherectomy, left
      pelvic/paraaortic lymphadenectomy, omentectomy and peritoneal biopsies. She
      received four cycles of bleomycin, etoposide and cisplatin, similar to high-risk
      germ cell cancers. She has received no further therapy and is eleven years from
      diagnosis without evidence of disease. CONCLUSION: This is the first long-term
      juvenile survivor managed with both fertility-sparing surgery and BEP (bleomycin,
      etoposide, cisplatin).

PMID- 27896309
TI  - Olfactory Stimulus Control and the Behavioral Pharmacology of Remembering.
AB  - Behavior analytic approaches and techniques have much to offer to the study of
      remembering. There is currently great interest in the development of animal
      models of human memory processes in order to enhance understanding of the
      neurobiology of memory and treatment of dementia and related disorders. Because
      rodent models are so important in contemporary neuroscience and genetics,
      development of procedures to study various forms of memory in rodents is a point
      of emphasis. The sense of smell plays an important role in rodent behavior and
      use of olfactory stimuli has permitted demonstrations of complex forms of
      stimulus control that have also served as baselines for studying drug effects on
      remembering. This article focuses on the effects of drugs on behavior maintained
      by two related procedures: delayed matching-to-sample with odors and the Odor
      Span Task. These types of procedures provide an opportunity to explore drug
      effects on behavior maintained by multiple stimuli and across a range of delay
      intervals with potential to advance analysis of the behavioral pharmacology of
      remembering.

PMID- 27896310
TI  - Preservation of Essential Odor-Guided Behaviors and Odor-Based Reversal Learning
      after Targeting Adult Brain Serotonin Synthesis.
AB  - The neurotransmitter serotonin (5-HT) is considered a powerful modulator of
      sensory system organization and function in a wide range of animals. The
      olfactory system is innervated by midbrain 5-HT neurons into both its primary and
      secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its
      receptors modulate olfactory system function, including odor information input to
      the olfactory bulb. It is unknown, however, whether the olfactory system requires
      5-HT for even its most basic behavioral functions. To address this question, we
      established a conditional genetic approach to specifically target adult brain
      tryptophan hydroxylase 2 (Tph2), encoding the rate-limiting enzyme in brain 5-HT
      synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel
      model, we investigated the behavior of 5-HT-depleted mice during performance in
      an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the
      forebrain, including the olfactory bulbs, had no detectable effect on the ability
      of mice to perform the odor-based task. Tph2-targeted mice not only were able to
      learn the task, but also had levels of odor acuity similar to those of control
      mice when performing coarse odor discrimination. Both groups of mice spent
      similar amounts of time sampling odors during decision-making. Furthermore, odor
      reversal learning was identical between 5-HT-depleted and control mice. These
      results suggest that 5-HT neurotransmission is not necessary for the most
      essential aspects of olfaction, including odor learning, discrimination, and
      certain forms of cognitive flexibility.

PMID- 27896311
TI  - Interfacing with Neural Activity via Femtosecond Laser Stimulation of Drug
      Encapsulating Liposomal Nanostructures.
AB  - External control over rapid and precise release of chemicals in the brain
      potentially provides a powerful interface with neural activity. Optical
      manipulation techniques, such as optogenetics and caged compounds, enable remote
      control of neural activity and behavior with fine spatiotemporal resolution.
      However, these methods are limited to chemicals that are naturally present in the
      brain or chemically suitable for caging. Here, we demonstrate the ability to
      interface with neural functioning via a wide range of neurochemicals released by
      stimulating loaded liposomal nanostructures with femtosecond lasers. Using a
      commercial two-photon microscope, we released inhibitory or excitatory
      neurochemicals to evoke subthreshold and suprathreshold changes in membrane
      potential in a live mouse brain slice. The responses were repeatable and could be
      controlled by adjusting laser stimulation characteristics. We also demonstrate
      the release of a wider range of chemicals-which previously were impossible to
      release by optogenetics or uncaging-including synthetic analogs of naturally
      occurring neurochemicals. In particular, we demonstrate the release of a
      synthetic receptor-specific agonist that exerts physiological effects on long
      term synaptic plasticity. Further, we show that the loaded liposomal
      nanostructures remain functional for weeks in a live mouse. In conclusion, we
      demonstrate new techniques capable of interfacing with live neurons, and
      extendable to in vivo applications.

PMID- 27896312
TI  - The Memory Trace Supporting Lose-Shift Responding Decays Rapidly after Reward
      Omission and Is Distinct from Other Learning Mechanisms in Rats.
AB  - The propensity of animals to shift choices immediately after unexpectedly poor
      reinforcement outcomes is a pervasive strategy across species and tasks. We
      report here that the memory supporting such lose-shift responding in rats rapidly
      decays during the intertrial interval and persists throughout training and
      testing on a binary choice task, despite being a suboptimal strategy. Lose-shift
      responding is not positively correlated with the prevalence and temporal
      dependence of win-stay responding, and it is inconsistent with predictions of
      reinforcement learning on the task. These data provide further evidence that win
      stay and lose-shift are mediated by dissociated neural mechanisms and indicate
      that lose-shift responding presents a potential confound for the study of choice
      in the many operant choice tasks with short intertrial intervals. We propose that
      this immediate lose-shift responding is an intrinsic feature of the brain's
      choice mechanisms that is engaged as a choice reflex and works in parallel with
      reinforcement learning and other control mechanisms to guide action selection.

PMID- 27896313
TI  - Effects of Paternal Predation Risk and Rearing Environment on Maternal Investment
      and Development of Defensive Responses in the Offspring.
AB  - Detecting past experiences with predators of a potential mate informs a female
      about prevailing ecological threats, in addition to stress-induced phenotypes
      that may be disseminated to offspring. We examined whether prior exposure of a
      male rat to a predator (cat) odor influences the attraction of a female toward a
      male, subsequent mother-infant interactions and the development of defensive
      (emotional) responses in the offspring. Females displayed less interest in males
      that had experienced predator odor. Mothers that reared young in larger,
      seminaturalistic housing provided more licking and grooming and active arched
      back-nursing behavior toward their offspring compared with dams housed in
      standard housing, although some effects interacted with paternal experience.
      Paternal predation risk and maternal rearing environment revealed sex-dependent
      differences in offspring wean weight, juvenile social interactions, and anxiety
      like behavior in adolescence. Additionally, paternal predator experience and
      maternal housing independently affected variations in crf gene promoter
      acetylation and crf gene expression in response to an acute stressor in
      offspring. Our results show for the first time in mammals that variation among
      males in their predator encounters may contribute to stable behavioral variation
      among females in preference for mates and maternal care, even when the females
      are not directly exposed to predator threat. Furthermore, when offspring were
      exposed to the same threat experienced by the father, hypothalamic crf gene
      regulation was influenced by paternal olfactory experience and early housing.
      These results, together with our previous findings, suggest that paternal stress
      exposure and maternal rearing conditions can influence maternal behavior and the
      development of defensive responses in offspring.

PMID- 27896316
TI  - Compound heterozygous intermediate MJD alleles cause cerebellar ataxia with
      sensory neuropathy.
AB  - Spinocerebellar degeneration (SCD) is a group of disorders characterized by
      progressive ataxia caused by dysfunction and atrophy of the cerebellum or its
      projections. Approximately one-third of SCD cases are familial SCD, the majority
      of which are attributed to CAG triplet repeat expansions including
      spinocerebellar ataxia (SCA)1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA6,
      SCA8, SCA12, SCA17, and dentate-rubro-pallido-luysian atrophy (DRPLA). The
      triplet repeat number of the alleles representing complete penetrance varies
      among diseases. Generally, there is a gap between the normal alleles and the
      complete penetrance alleles. Rarely, intermediate alleles with the repeat numbers
      between the abnormal and normal ranges are observed, although the implications of
      these intermediate alleles remain ambiguous.

PMID- 27896317
TI  - Video-game-assisted physiotherapeutic scoliosis-specific exercises for idiopathic
      scoliosis: case series and introduction of a new tool to increase motivation and
      precision of exercise performance.
AB  - BACKGROUND: It is important to monitor how patients with juvenile and adolescent
      idiopathic scoliosis comply with their physiotherapeutic scoliosis-specific
      exercises (PSSE). Physiogame, a newly developed video game using the Game-Trak 3D
      interactive game controller, combines correct PSSE performance with gaming. It
      tracks the position of the working limb in 3D space during the exercises as
      participants aim to hit certain targets and avoid others, and gives direct
      feedback by stopping the game if the working limb leaves the target 3D space,
      which is chosen to secure the corrective position according to the Schroth
      method. Physiogame records the quality and frequency of the exercises performed.
      We aimed to investigate the influence of this tool on motivation to perform
      regularly and, correctly, and with self-assessment of performance quality.
      METHODS: This case series included 8 consecutive patients with idiopathic
      scoliosis (thoracolumbar 7, lumbar 1), ages 7-13 years, all female and treated
      according to SOSORT guidelines; the COBB angle of primary curve at the start of
      brace therapy was 22-34 degrees . In addition to Full Time Rigid Bracing (FTRB,
      Cheneau) and PSSE (Schroth), the participants were to perform two standardized
      Schroth exercises (muscle cylinder in standing position, mainly addressing the
      thoracic curve, and in side-lying position, mainly addressing the lumbar curve)
      with video game assistance every day for 6 months. The development (first to last
      month) of the following parameters was analyzed with descriptive methods: the
      actual training time to assess motivation, the ratio of the actual playing time
      versus total playing time to assess exercise improvement, and self-assessment of
      quality of performance. RESULTS: The average number of sessions with Physiogame
      was 217 per study participant (range 24 to 572, the study protocol targeted at
      least 180); actual training time decreased from 79 to 52 min (first to last
      month). Actual playing time increased from 73% of the total playing time to 83%
      (first to last month), and positive hits per second from 0.33 to 0.56. Self
      assessment increased from "good" to "very good". The curve angles ( degrees Cobb)
      were maintained over the study period (upper thoracic mean -1.3 degrees , median 
      1 degrees ; lower thoracic mean 3 degrees , median 2 degrees ; lumbar mean 0.5,
      median 0). CONCLUSIONS: The improvement we saw in exercise performance, is
      thought to result primarily from the direct given feedback during the game, as
      the exercises themselves were already familiar to the patients. The synchronous
      recording of actual training time allows evaluation of Schroth therapy for
      idiopathic scoliosis, since both prescribed training time and actual training
      time are captured. No comparable tool was found in literature.

PMID- 27896315
TI  - Altered Oscillatory Dynamics of CA1 Parvalbumin Basket Cells during Theta-Gamma
      Rhythmopathies of Temporal Lobe Epilepsy.
AB  - Recent reports in human demonstrate a role of theta-gamma coupling in memory for
      spatial episodes and a lack of coupling in people experiencing temporal lobe
      epilepsy, but the mechanisms are unknown. Using multisite silicon probe
      recordings of epileptic rats engaged in episodic-like object recognition tasks,
      we sought to evaluate the role of theta-gamma coupling in the absence of
      epileptiform activities. Our data reveal a specific association between theta
      gamma (30-60 Hz) coupling at the proximal stratum radiatum of CA1 and spatial
      memory deficits. We targeted the microcircuit mechanisms with a novel approach to
      identify putative interneuronal types in tetrode recordings (parvalbumin basket
      cells in particular) and validated classification criteria in the epileptic
      context with neurochemical identification of intracellularly recorded cells. In
      epileptic rats, putative parvalbumin basket cells fired poorly modulated at the
      falling theta phase, consistent with weaker inputs from Schaffer collaterals and
      attenuated gamma oscillations, as evaluated by theta-phase decomposition of
      current-source density signals. We propose that theta-gamma interneuronal
      rhythmopathies of the temporal lobe are intimately related to episodic memory
      dysfunction in this condition.

PMID- 27896318
TI  - Insulin elevates leptin secretion and mRNA levels via cyclic AMP in 3T3-L1
      adipocytes deprived of glucose.
AB  - AIMS: Leptin plays an important role in the pathogenesis of obesity and diabetes,
      yet the regulatory mechanisms of this hormone have not been fully elucidated. In
      this study, we aimed to clarify the roles of insulin and glucose in leptin
      secretion and mRNA production using inhibitors of insulin signal transduction in
      adipocytes cultured under glucose-free or normal conditions. METHODS:
      Differentiated 3T3-L1 adipocytes were stimulated with insulin in combination with
      inhibitors for phosphoinositide 3-kinase (PI3K), Akt, and phosphodiesterase 3B
      (PDE3B), as well as epinephrine and a cyclic AMP (cAMP) analog under glucose-free
      or normal conditions. After 8 h of stimulation, leptin protein levels in the
      media and leptin mRNA expression levels in the adipocytes were measured. RESULTS:
      Insulin significantly increased the secretion and mRNA levels of leptin under the
      depletion of glucose. Glucose augmented basal leptin secretion without insulin,
      while glucose nullified insulin-induced leptin mRNA upregulation. The PI3K
      inhibitor BEZ-235, the Akt inhibitor MK-2206, and the PDE3B inhibitor cilostazol
      attenuated the insulin stimulation of leptin secretion, but did not suppress the
      insulin-induced leptin mRNA upregulation with glucose depletion. In contrast to
      the glucose-free condition, insulin failed to upregulate leptin mRNA in the
      presence of glucose. The cAMP analog dibutyryl cAMP and epinephrine decreased
      both leptin secretion and mRNA regardless of glucose supplementation. CONCLUSION:
      Insulin alone stimulates leptin secretion and elevates leptin mRNA levels via
      cAMP under the lack of glucose metabolism, while glucose is a significant and
      ambivalent effector on the insulin effects of leptin.

PMID- 27896319
TI  - Correlation between pollution and decline of Scleractinian Cladocora caespitosa
      (Linnaeus, 1758) in the Gulf of Gabes.
AB  - During an expedition in 2014 in the Gulf of Gabes that aimed to evaluate the
      impact of the pollution of the phosphate industry on the marine environment,
      numerous dead coral fragments were retrieved from several stations along a 18 km
      long transect in front of the industry complex of Gabes. Detailed taxonomy of
      these coral fragments shows clearly that all fragments belong to the species
      Cladocora caespitosa (Linnaeus, 1758). Quantitative analysis of the coral
      fragments indicates a positive correlation with stations characterized by
      positive bathymetric anomalies. We suggest the presence of probable small-scaled
      (up to 4 m high) biogenic (palaeo-) build-ups composed mainly of coral colonies
      and bryozoans. Radiocarbon dating of three coral fragments show ages as old as
      1897, 1985 and 1986 AD and suggests the presence of living C. caespitosa as close
      as 6 km to the phosphate treatment industry of Gabes at least until 1986 AD. This
      latter age coincides with the construction of the ammonium phosphate production
      plant, in 1979, in the Gulf of Gabes with an increase of the natural phosphate
      production. The higher impact of pollution on the marine environment in the inner
      part of the Gulf of Gabes likely induced the decline of C. caespitosa. This is
      well in agreement with enhanced siltation processes suggested by the sedimentary
      facies and grain-size analyses presently characterizing the Gulf of Gabes
      nowadays.

PMID- 27896314
TI  - Graph Theoretic and Motif Analyses of the Hippocampal Neuron Type Potential
      Connectome.
AB  - We computed the potential connectivity map of all known neuron types in the
      rodent hippocampal formation by supplementing scantly available synaptic data
      with spatial distributions of axons and dendrites from the open-access knowledge
      base Hippocampome.org. The network that results from this endeavor, the broadest
      and most complete for a mammalian cortical region at the neuron-type level to
      date, contains more than 3200 connections among 122 neuron types across six
      subregions. Analyses of these data using graph theory metrics unveil the
      fundamental architectural principles of the hippocampal circuit. Globally, we
      identify a highly specialized topology minimizing communication cost; a modular
      structure underscoring the prominence of the trisynaptic loop; a core set of
      neuron types serving as information-processing hubs as well as a distinct group
      of particular antihub neurons; a nested, two-tier rich club managing much of the
      network traffic; and an innate resilience to random perturbations. At the local
      level, we uncover the basic building blocks, or connectivity patterns, that
      combine to produce complex global functionality, and we benchmark their
      utilization in the circuit relative to random networks. Taken together, these
      results provide a comprehensive connectivity profile of the hippocampus, yielding
      novel insights on its functional operations at the computationally crucial level
      of neuron types.

PMID- 27896320
TI  - Influences of "do-not-resuscitate order" prohibition on CPR outcomes.
AB  - OBJECTIVES: The aim of the study is to determine factors affecting the return of
      spontaneous circulation (ROSC) ratios, neurological outcomes at discharge, the
      ratio of living patients discharged from the hospital and due to Do not attempt
      resuscitation (DNAR) prohibition. MATERIAL AND METHODS: This is a retrospective
      observational study conducted on patients of cardiopulmonary resuscitation (CPR)
      performed in emergency department (ED) and intensive care units between February
      2010 and February 2012. RESULTS: A total of 469 patients were evaluated, and 266
      eligible patients who did not have DNAR orders were included in the study.
      Overall, 45.1% of the adult in-hospital cardiac arrest victims returned to
      spontaneous circulation, and 5.3% survived to hospital discharge. Of the patients
      who were discharged alive from the hospital, 33.3% were discharged in poor
      neurologic conditions of Cerebral Performance Category (CPC) score 3 or 4. The
      ROSC ratio was reduced for the patients with malignancies compared to the
      patients with other preexisting conditions (OR: 12.783; 95% CI 2.967-55.072; p =
      0.000). None of the patients with malignancies were discharged alive from the
      hospital. Only one patient with end-stage disease was discharged alive from
      hospital, and this patient's CPC score was 4. DISCUSSION AND CONCLUSION: CPR has
      not increased the ROSC and alive discharge rates in patients with malignancy and
      end-state disease. DNAR order prohibition have been increased the futile CPR
      attempts. DNAR should be accepted as a human right that represents an honorable
      death option and whether a DNAR is order demanded should be specifically
      discussed with patients with malignancies and end-stage disease presenting to ED.

PMID- 27896321
TI  - Comparison of the C-MAC video laryngoscope to the Macintosh laryngoscope for
      intubation of blunt trauma patients in the ED.
AB  - OBJECTIVES: We aimed to compare the performance of the C-MAC video laryngoscope
      (C-MAC) to the Macintosh laryngoscope for intubation of blunt trauma patients in
      the ED. MATERIAL AND METHODS: This was a prospective randomized study. The
      primary outcome measure is overall successful intubation. Secondary outcome
      measures are first attempt successful intubation, Cormack-Lehane (CL) grade, and
      indicators of the reasons for unsuccessful intubation at the first attempt with
      each device. Adult patients who suffered from blunt trauma and required
      intubation were randomized to video laryngoscopy with C-MAC device or direct
      laryngoscopy (DL). RESULTS: During a 17-month period, a total of 150 trauma
      intubations were performed using a C-MAC and DL. Baseline characteristics of
      patients were similar between the C-MAC and DL group. Overall success for the C
      MAC was 69/75 (92%, 95% CI 0.83 to 0.96) while for the DL it was 72/75 (96%, 95%
      CI 0.88 to 0.98). First attempt success for the C-MAC was 47/75 (62.7%, 95% CI
      0.51 to 0.72) while for the DL it was 44/75 patients (58.7%, 95% CI 0.47 to
      0.69). The mean time to achieve successful intubation was 33.4 +/- 2.5 s for the
      C-MAC versus 42.4 +/- 5.1 s for the DL (p = 0.93). There was a statistically
      significant difference between the DL and C-MAC in terms of visualizing the
      glottic opening and esophageal intubation in favor of the C-MAC (p = 0.002 and p
      = 0.013 respectively). DISCUSSION AND CONCLUSION: The overall success rates were
      similar. The C-MAC demonstrated improved glottic view and decrease in esophageal
      intubation rate.

PMID- 27896322
TI  - Effectiveness of the synthetic cannabinoids seminar.
AB  - OBJECTIVES: Synthetic cannabinoid or "Bonzai" use is a public health issue as its
      use has increased in Turkey as well as all over the world. The aim of this study
      is to evaluate the effectiveness of the "Synthetic Cannabinoids Seminar" that was
      provided to physicians who work in emergency services, using multiple choice
      questionnaires before and after the seminar as a tool for evaluation. MATERIAL
      AND METHOD: Synthetic cannabinoids seminars were provided to physicians who work
      in emergency services in two different cities, with the participation of 20
      physicians in each scheduled seminar. The seminars were instructed by emergency
      medicine specialists and psychiatrists who were certified as an instructor by the
      Turkish Ministry of Health, after receiving an instructor course in synthetic
      cannabinoids. In order to measure basal knowledge levels of the participants, a
      pretest was performed for all participants before the seminar. After the seminar,
      a posttest was performed using the same questions in the pretest. The number of
      correct answers in both tests was then compared. RESULTS: In total, 85
      individuals attended the seminars; 29 individuals from Dumlupinar University
      Evliya Celebi Training and Research Hospital constituted first group, and 56
      individuals from Denizli State Hospital constituted second group. In both groups,
      the ratios of correct answers in the posttest were determined to be higher when
      compared to the pretest. CONCLUSION: The seminars on synthetic cannabinoids are
      useful and necessary for physicians.

PMID- 27896323
TI  - Intra-articular lidocaine versus intravenous sedative and analgesic for reduction
      of anterior shoulder dislocation.
AB  - OBJECTIVE: This prospective clinical trial was performed to compare the safety
      and efficiency of intra-articular lidocaine (IAL) versus intravenous sedative and
      analgesic (IVSA) in reduction of anterior shoulder dislocation. MATERIALS AND
      METHODS: Patients with anterior shoulder dislocation were randomly divided into 2
      groups to receive IAL and IVSA. One group patients received an intravenous dose
      of 0.05 mg/kg midazolam and 1 MUg/kg fentanyl, while the other group received 20
      mL intra-articular lidocaine (1%). Patient satisfaction (via a standard 5-choice
      questionnaire), pain score (based on visual analog scale ranging from 0 to 10
      points), comfort reduction, recovery time, and side effects were recorded and
      compared between the two groups before, during and after the reduction procedure.
      RESULTS: Totally 104 patients with acute anterior shoulder dislocation and the
      mean age of 28.75 +/- 7.24 years were included (86.5% male). There was no
      statistically significant difference between IAL and IVSA groups regarding age (p
      = 0.45) and gender (p = 0.25). A total of forty-seven (45.2%) patients,
      distributed in both groups, had a history of anterior shoulder dislocation. A
      significant difference was seen with regard to diminished pain intensity during
      reduction in IAL group (p < 0.001); Complications including nausea, apnea,
      hypoxia and headache were only observed in IVSA group, and there was no adverse
      effect in IAL group; increased patient satisfaction in IVSA group (p = 0.007);
      similar success rate at first attempt of reduction in both groups, and a shorter
      time to discharge in IAL group (p < 0.001). CONCLUSION: It seems that the use of
      intra-articular lidocaine for reduction of anterior shoulder dislocation is
      effective, safe, and time saving in the emergency department and has few
      complications. It can be considered as the first line analgesia in managing
      anterior shoulder dislocation.

PMID- 27896324
TI  - The relationship between anemia and recurrence of ischemic stroke in patients
      with Trousseau's syndrome: A retrospective cross-sectional study.
AB  - OBJECTIVES: The relationship between cancer and thrombosis was first recognized
      by the French internist Armand Trousseau in 1865. Trousseau's syndrome is a
      spectrum of symptoms that result from recurrent thromboembolism associated with
      cancer or malignancy-related hypercoagulability. In this study, we investigated
      whether demographics, clinical features, or laboratory findings were able to
      predict recurrent stroke episodes in patients with Trousseau's syndrome. METHODS:
      In total, 178 adult patients were enrolled in this retrospective cross-sectional
      study. All patients had been admitted to the emergency room of our hospital
      between January 2011 and September 2014 and were diagnosed with acute ischemic
      stroke. Patients were divided into two groups: patients with malignancy
      (Trousseau's syndrome), and patients without malignancy. RESULTS: There were
      several significant differences between the laboratory results of the two patient
      groups. For patients with Trousseau's, the hemoglobin levels for those with one
      stroke was 12.29 +/- 1.81, while those in patients who had experienced more than
      one stroke was 10.94 +/- 2.14 (p = 0.004). CONCLUSIONS: Trousseau's syndrome is a
      cancer-associated coagulopathy associated with high morbidity and mortality
      rates. In this study, anemia was associated with increased stroke recurrence in
      patients with malignancy (Trousseau's syndrome).

PMID- 27896325
TI  - Utilization of plasmapheresis for organophosphate intoxication: A case report.
AB  - Organophosphate (OP) compounds are extremely toxic chemicals that may be absorbed
      via skin, conjunctiva, gastrointestinal and respiratory systems. Treatment of OP
      poisoning is a critical and aggressive process which includes decontamination,
      antidote administration (atropin and oximes), mechanical ventilation support and
      extracorporeal elimination procedures if needed. Here we present a young female
      patient who was unintentionally poisoned by an OP (trichlorfon) after using it to
      moisture her skin. The importance of this patient is the dermal disease that
      makes her unprotective to dermal exposure of chemicals and application of
      plasmapheresis to treat her poisoning.

PMID- 27896326
TI  - Preoperative diagnosis of Amyand's hernia by ultrasound and computed tomography.
AB  - Inguinal hernia is the most common seen groin hernias which mostly contain bowel.
      The incidence of vermiform appendix in an inguinal hernia is seen in 1% of all
      inguinal hernia. This is known as Amyand's hernia. Appendix within a hernia can
      be normal or complicated by appendicitis. Most of these cases are not diagnosed
      preoperatively and managed during surgery. Preoperative diagnosis of these cases
      is so rare. Very few cases have been reported so far. In our case, we diagnosed
      an inflamed appendix in a 49 years old female within right inguinal hernia by
      using ultrasound and confirmed it by CT scan.

PMID- 27896327
TI  - A case of mediastinitis accompanied with hyperosmolar nonketotic coma.
AB  - Mediastinitis is a serious infection involving mediastinal spaces after cervical
      infections spread along the facial planes. A late diagnosis of mediastinitis may
      result in death. Here we present a diabetic patient suffered from mediastinit
      accompanied with hyperosmolar nonketotic coma. A 61 years old male patient with
      type 2 diabetes was admitted to our hospital, with complaint of generalized
      worsening and fever. A diagnosis of nonketotic hyperosmolar coma was done and
      proper treatment started immediately. Neck tomography revealed abscess formation
      in the upper mediastinum. The needle aspirat culture failed to show bacterial
      growth. After five days of antibiotic treatment the patient's symptoms resolved.
      The abscess formation and pleural effusion almost disappeared on control
      tomography. No similar case presentation was seen in the current literature.
      Apart from this case, mediastinit should be keep in mind when a patient suffered
      from dysphagia, fever and cervical swelling.

PMID- 27896328
TI  - Liver laceration related to cardiopulmonary resuscitation.
AB  - Cardiopulmonary resuscitation (CPR) is recognized as a medical procedure
      performed to maintain vital functions of a person whose cardiac and respiratory
      functions have stopped. Chest compression is the most essential component of CPR
      and it is performed on the lower half of the sternum. During CPR, many
      complications may occur because of chest compressions, especially chest injuries
      including sternum and rib fractures. Rarely tracheal injury, rupture of the
      stomach, or liver or spleen injury may also occur as complications. In this
      study, we present two cases of liver injury caused by resuscitation. With this
      article, we want to emphasize the importance of making correct chest
      compressions.

PMID- 27896330
TI  - Biventricular thrombus in hypereosinophilic syndrome presenting with shortness of
      breath.
AB  - A 48 years old male presented to clinic with 12 months of low grade fever with
      shortness of breath which has progressively worsened with no associated weight
      loss, night sweats or loss of appetite. There was no prior history of chronic
      illness before the current illness. Laboratory workup revealed a high white blood
      cell count with predominant eosinophils. Chest X-ray was normal. Transthoracic
      echocardiography and Cardiac Magnetic Resonance showed biventricular thrombi. On
      further extensive workup the findings were consistent with hypereosinophilic
      syndrome. The patient was started on oral steroids, hydroxyurea, imatanib
      mesylate and oral anticoagulation. The patient responded to the treatment with
      complete resolution of his symptoms over the course of few months. The repeat
      Echocardiogram after a year showed normal left ventricular systolic and diastolic
      function with complete resolution of biventricular thrombi.

PMID- 27896329
TI  - Myasthenia gravis with acute respiratory failure in the emergency department.
AB  - Acute respiratory failure (ARF) is defined as a sudden malfunction in the ability
      of respiratory system to maintain adequate gas exchange. Acute hypercapnic
      respiratory failure develops as a result of ventilation deficiency and it is
      defined as an increase of PaCO2 above 45 mmHg. Myasthenia Gravis (MG) is a
      sporadically developing auto-immune deficiency where the neuro-muscular
      transmission is affected and it is one of the important reasons for
      neurologically-induced respiratory distress. Here, we report a case of a 75-year
      old male patient previously undiagnosed MG, who presented with ARF. MG is not a
      common entity that we encounter daily. Patients on occasions may present to the
      emergency department because of acute exacerbation. Though most of them were
      known cases, we should be aware of some unrecognized cases and should consider MG
      as a differential diagnosis for patients with acute respiratory failure.

PMID- 27896331
TI  - Successful selective arterial thrombolysis in patient with acute abdominal
      thromboembolism.
AB  - The paper reports successful thrombolysis conducted in 64 years old woman
      admitted to the clinic with clinical and angiographic data for acute surgical
      abdomen caused by acute tromboembolia of arteria mesenterica superior (AMS). The
      therapeutic approach required to undertake lifesaving decision on i.e. surgical
      vs. invasive treatment in conditions of emergency. Finally, it was decided to
      undertake invasive treatment with successful restoration of blood flow in the
      related artery. The patient was discharged from the clinic with considerable
      clinical improvement on the fifth day of her stay. The case report includes
      discussion on issues relating the consequence of the diagnostic and
      interventional procedures in such patients, opportunities for conducting
      emergency thrombolysis in acute embolia of AMS and preventive measures in
      patients with high tromboembolic risk.

PMID- 27896333
TI  - Shoulder pain after falling from bicycle.

PMID- 27896332
TI  - Acute pelvic pain in female with ruptured ectopic pregnancy: Magnetic Resonance
      Imaging as problem solving tool.

PMID- 27896335
TI  - A Rare Case of a Symptomatic Sternalis Muscle: Ultrasonograpy And MRI
      Correlation.

PMID- 27896334
TI  - Ultrasound Vascular Elastography as a Tool for Assessing Atherosclerotic Plaques 
      A Systematic Literature Review.
AB  - Atherosclerosis is a widespread disease that accounts for nearly 3-quarters of
      deaths due to cardiovascular disease. Ultrasound elastography might be able to
      reliably identify characteristics associated with vulnerable plaques. There is a
      need for the evaluation of elastography and its ability to distinguish between
      vulnerable and stable plaques. The aim of this paper is to provide an overview of
      the literature on vascular elastography. A systematic search of the available
      literature for studies using elastography for assessing atherosclerotic plaques
      was conducted using the MEDLINE, Embase, Cochrane Library and Web of Science
      databases. A standardized template was used to extract relevant data following
      the PRISMA 2009 checklist. 20 articles were included in this paper. The studies
      were heterogeneous. All studies reported that elastography was a feasible
      technique and provided additional information compared to B-mode ultrasound
      alone. Most studies reported higher strain values for vulnerable plaques.
      Ultrasound elastography has potential as a clinical tool in the assessment of
      atherosclerotic plaques. Elastography is able to distinguish between different
      plaque types, but there is considerable methodological variation between studies.
      There is a need for larger studies in a clinical setting to determine the full
      potential of elastography.

PMID- 27896336
TI  - CuI-Catalyzed intramolecular aminocyanation of terminal alkynes in N-(2
      ethynylphenyl)-N-sulfonylcyanamides via Cu-vinylidene intermediates.
AB  - CuI-Catalyzed intramolecular aminocyanation of terminal alkynes in N-(2
      ethynylphenyl)-N-sulfonylcyanamides was initiated by the formation of Cu
      acetylide to trigger N-CN bond cleavage of the N-sulfonylcyanamide moiety
      followed by CN migration to form a beta-cyano Cu-vinylidene intermediate.
      Subsequently, the indole ring closure furnished the corresponding 1-sulfonyl-3
      cyanoindoles.

PMID- 27896337
TI  - A multicomponent assembly approach for the design of deep desulfurization
      heterogeneous catalysts.
AB  - Deep desulfurization is a challenging task and global efforts are focused on the
      development of new approaches for the reduction of sulfur-containing compounds in
      fuel oils. In this work, we have proposed a new design strategy for the
      development of deep desulfurization heterogeneous catalysts. Based on the adopted
      design strategy, a novel composite material of polyoxometalate (POM)-based ionic
      liquid-grafted layered double hydroxides (LDHs) was synthesized by an
      exfoliation/grafting/assembly process. The structural properties of the as
      prepared catalyst were characterized using FT-IR, XRD, TG, NMR, XPS, BET, SEM and
      HRTEM. The heterogeneous catalyst exhibited high activity in deep desulfurization
      of DBT (dibenzothiophene), 4,6-DMDBT (4,6-dimethyldibenzothiophene) and BT
      (benzothiophene) at 70  degrees C in 25, 30 and 40 minutes, respectively. The
      catalyst can be easily recovered and reused at least ten times without obvious
      decrease of its catalytic activity. Such excellent sulfur removal ability as well
      as the cost efficiency of the novel heterogeneous catalyst can be attributed to
      the rational design, where the spatial proximity of the substrate and the active
      sites, the immobilization of ionic liquid onto the LDHs via covalent bonding and
      the recyclability of the catalyst are carefully considered.

PMID- 27896338
TI  - Electrochemical investigation of [Co4(MU3-O)4(MU-OAc)4(py)4] and peroxides by
      cyclic voltammetry.
AB  - Two oxidative redox processes of the neutral cobalt(iii) cubane, [Co4(MU3-O)4(MU
      OAc)4(py)4], were investigated by cyclic voltammetry at a glassy carbon electrode
      in acetonitrile. In addition to the first quasi-reversible one-electron oxidation
      at E1/2 = 0.283 V vs. Fc0/+, a second quasi-reversible one-electron oxidation was
      observed at E1/2 = 1.44 V vs. Fc0/+. Oxidation at this potential does not
      facilitate water oxidation. In the presence of tert-butylhydroperoxide the peak
      current of this second oxidation increases, suggesting oxidation of the peroxide
      by the doubly oxidised cubane.

PMID- 27896339
TI  - Intramolecular dehydration of biomass-derived sugar alcohols in high-temperature
      water.
AB  - The intramolecular dehydration of biomass-derived sugar alcohols d-sorbitol, d
      mannitol, galactitol, xylitol, ribitol, l-arabitol, erythritol, l-threitol, and
      dl-threitol was investigated in high-temperature water at 523-573 K without the
      addition of any acid catalysts. d-Sorbitol and d-mannitol were dehydrated into
      isosorbide and isomannide, respectively, as dianhydrohexitol products. Galactitol
      was dehydrated into anhydrogalactitols; however, the anhydrogalactitols could not
      be dehydrated into dianhydrogalactitol products because of the orientation of the
      hydroxyl groups at the C-3 and C-6 positions. Pentitols such as xylitol, ribitol,
      and l-arabitol were dehydrated into anhydropentitols. The dehydration rates of
      the pentitols containing hydroxyl groups in the trans form, which remained as
      hydroxyl groups in the product tetrahydrofuran, were larger than those containing
      hydroxyl groups in the cis form because of the structural hindrance caused by the
      hydroxyl groups in the cis form during the dehydration process. In the case of
      the tetritols, the dehydration of erythritol was slower than that of threitol,
      which could also be explained by the structural hindrance of the hydroxyl groups.
      The dehydration of l-threitol was faster than that of dl-threitol, which implies
      that molecular clusters were formed by hydrogen bonding between the sugar
      alcohols in water, which could be an important factor that affects the
      dehydration process.

PMID- 27896340
TI  - One-step fabrication of porous oxygen-doped g-C3N4 with feeble nitrogen vacancies
      for enhanced photocatalytic performance.
AB  - Porous oxygen-doped graphitic carbon nitride (g-C3N4) with feeble nitrogen
      vacancies was fabricated through thermal polycondensation of melamine with an
      appropriate amount of polyvinylpyrrolidone. After optimization, the bandgap of g
      C3N4 can be narrowed by 0.2 eV and the specific surface area expanded, which
      contribute to increasing the utilization of solar energy. Consequently, the
      optimized g-C3N4 exhibits impressive enhancement in photocatalytic hydrogen
      evolution performance, by nearly 5 times compared with the pristine one under the
      irradiation of visible light.

PMID- 27896341
TI  - Energetics of CO oxidation on lanthanide-free perovskite systems: the case of Co
      doped SrTiO3.
AB  - The energetics of the catalytic oxidation of CO on a complex metal oxide are
      investigated for the first time via density functional theory calculations. The
      catalyst, Co-doped SrTiO3, is modelled using periodically repeated slabs based on
      the SrTiO3(100) surface. The comparison of the energy profiles obtained for the
      pure host and the Co-doped material reveals the actual pathway followed by the
      reaction, and shows that Co doping enhances the catalytic properties of SrTiO3 by
      reducing the energy cost for the formation of oxygen vacancies.

PMID- 27896342
TI  - Micellization of alkyltrimethylammonium bromide surfactants in choline
      chloride:glycerol deep eutectic solvent.
AB  - Deep eutectic solvents have shown the ability to promote the self-assembly of
      surfactants in solution. However, some differences have been found compared with
      self-assembly in pure water and other polar organic solvents. The behaviour of
      alkyltrimethylammonium bromides in choline chloride:glycerol deep eutectic
      solvent has been studied by means of surface tension, X-ray and neutron
      reflectivity and small-angle neutron scattering. The surfactants were found to
      remain surface active and showed comparable critical micelle concentrations to
      the same surfactants in water. Our scattering studies demonstrate that these
      surfactants form globular micelles with ellipsoidal shape in solution. The size,
      shape and aggregation number of the aggregates were found to vary with the chain
      length of the surfactant. Specific solvent-headgroup interactions were not found
      in this system, unlike those we have previously postulated for anionic
      surfactants in choline chloride deep eutectic solvents.

PMID- 27896344
TI  - Thermodynamics and kinetics of graphene chemistry: a graphene hydrogenation
      prototype study.
AB  - The thermodynamic and kinetic controls of graphene chemistry are studied
      computationally using a graphene hydrogenation reaction and polyaromatic
      hydrocarbons to represent the graphene surface. Hydrogen atoms are concertedly
      chemisorped onto the surface of graphene models of different shapes (i.e., all
      zigzag, all-armchair, zigzag-armchair mixed edges) and sizes (i.e., from 16-42
      carbon atoms). The second-order Z-averaged perturbation theory (ZAPT2) method
      combined with Pople double and triple zeta basis sets are used for all
      calculations. It is found that both the net enthalpy change and the barrier
      height of graphene hydrogenation at graphene edges are lower than at their
      interior surfaces. While the thermodynamic product distribution is mainly
      determined by the remaining pi-islands of functionalized graphenes (Phys. Chem.
      Chem. Phys., 2013, 15, 3725-3735), the kinetics of the reaction is primarily
      correlated with the localization of the electrostatic potential of the graphene
      surface.

PMID- 27896345
TI  - High performance flexible strain sensor based on self-locked overlapping graphene
      sheets.
AB  - Strain sensors have been widely used in the fields of wearable devices, robot
      arms, medical sensing, bio-sensing, artificial skin and so on, but the existing
      strain sensors have some shortcomings such as a limited gauge factor (GF) or
      strain range. We fabricate a novel and flexible strain sensor with high
      performance based on self-locked overlapping graphene sheets (SOGS) which can be
      used for wearable devices. Polydimethylsiloxane (PDMS) is used to lock the
      overlapping graphene sheets, and then the graphene can be stretched and achieve
      an ultrahigh GF. In addition, a new theory is put forward to explain the GF
      changes with strain range for the SOGS strain sensor. In this work, graphene
      oxide (GO) film is reduced to reduced GO (rGO) by a laser. Then, the SOGS and
      electrodes are encapsulated by PDMS. The SOGS strain sensor has a high GF up to
      400 and strain range over 7.5%, and this SOGS strain sensor achieves a balance
      between high sensitivity and large strain range compared with other existing
      strain sensors. Furthermore the theoretical equation based on the new theory
      agrees well with the experimental results. And this strain sensor can be used in
      many applications because of its high sensitivity. Some applications of the SOGS
      strain sensors are demonstrated for the detection of various human motions and
      human sounds. The SOGS strain sensor can exhibit great potential in wearable
      electronics because of its good balance between high sensitivity and large
      strain.

PMID- 27896343
TI  - Electronic and non-adiabatic dynamics: general discussion.

PMID- 27896346
TI  - Visible light driven mesoporous Ag-embedded ZnO nanocomposites: reactive oxygen
      species enhanced photocatalysis, bacterial inhibition and photodynamic therapy.
AB  - We present here the multitasking capabilities of Ag-embedded ZnO nanocomposites
      (Ag-ZnO NCs), which include the photocatalytic degradation of organic dyes,
      bacterial inhibition, and cancer therapeutics. Ag-embedded ZnO nanocomposites (Ag
      ZnO NCs) of mesoporous spherical morphology (size ~ 150 +/- 50 nm) are
      successfully synthesized by a facile and single step soft-chemical approach. To
      understand the effect of Ag loading on multitasking properties, Ag-ZnO NCs are
      synthesized with different wt% of Ag. It was found that Ag5-ZnO NCs (5 wt% of Ag)
      showed excellent solar light-induced photocatalytic degradation properties
      against both cationic as well as anionic dyes. In addition, the presence of Ag in
      these NCs makes them strongly antibacterial, and kills 100% Escherichia coli (E.
      coli) cells within 2 hours (under dark), and within 30 min (under solar light).
      The enhanced photocatalytic and antibacterial activity of Ag-ZnO NCs is due to
      the anchoring of Ag NPs onto ZnO as well as minor substitution of Ag ions in the
      lattice of ZnO. This produces abundant charge carriers and generates
      significantly enhanced reactive oxygen species (ROS), which seem responsible for
      the multitasking properties. Furthermore, the cytotoxic study shows that Ag5-ZnO
      NCs kill oral carcinoma (KB) cells under visible light irradiation, and work as
      photosensitizers towards the photodynamic therapy of cancer due to the excellent
      photocatalytic activity. The high ROS concentration depolarizes the mitochondrial
      membrane potential, which in turn initiates apoptosis in oral carcinoma (KB)
      cells inducing cell death. Therefore, the as-prepared mesoporous Ag-ZnO NCs show
      great promise in waste water treatment, and cancer therapeutics.

PMID- 27896347
TI  - First-principles study of pressure-induced structural phase transitions in MnF2.
AB  - In this work we report a complete structural and magnetic characterization of
      crystalline MnF2 under pressure obtained using first principle calculations.
      Density functional theory was used as the theoretical framework, within the
      generalized gradient approximation plus the Hubbard formalism (GGA+U) necessary
      to describe the strong correlations present in this material. The vibrational,
      the magnetic exchange couplings and the structural characterization of MnF2 in
      the rutile ground state structure and potential high pressure phases are
      reported. The quasiharmonic approximation has been used to obtain the free
      energy, which at the same time is used to evaluate the different structural
      transitions at 300 K. Based on previous theoretical and experimental studies on
      AF2 compounds, ten different structural candidates were considered for the high
      pressure regime, which led us to propose a path for the MnF2 structural
      transitions under pressure. As experimental pressure settings can lead to non
      hydrostatic conditions, we consider hydrostatic and non-hydrostatic strains in
      our calculations. According to our results we found the following sequence for
      the pressure-driven structural phase transition in MnF2: rutile (P42/mnm) ->
      alpha-PbO2-type (Pbcn) -> dist. HP PdF2-type (Pbca) -> dist. fluorite (I4/mmm) ->
      cotunnite (Pnma). This structural path is correlated with other phase transitions
      reported on other metal rutile fluorides. In particular, we found that our
      proposed structural phase transition sequence offers an explanation of the
      different paths observed in the literature by taking into account the role of the
      hydrostatic conditions. In order to get a deep understanding of the modifications
      of MnF2 under pressure, we have analyzed the pressure evolution of the
      structural, vibrational, electronic, and magnetic properties for rutile and for
      each of the high pressure phases.

PMID- 27896348
TI  - Reaction rate theory: summarising remarks.
AB  - This paper summarizes the contributions to the Faraday Discussion on reaction
      rate theory. The topics range from contemporary usage of transition state theory,
      including rare event sampling, to instantons and non-adiabatic dynamics.

PMID- 27896349
TI  - Silver nanoparticles: a mechanism of action on moulds.
AB  - Silver nanoparticles (AgNPs) are widely used in all branches of industry.
      However, their mechanisms of action towards moulds have not been studied yet.
      Thus we conducted this study in which we have used laser desorption/ionization
      time-of-flight mass spectrometry (LDI-ToF-MS) analysis to determine metabolomic
      changes, and microscopic analysis (transmission electron microscopy, fluorescent
      microscopy) to observe changes in mould cells. The AgNP treatment caused the
      downregulation of 162 (15 ppm) and 284 (62 ppm), and 19 (15 ppm) and 29 (62 ppm)
      metabolites of Aspergillus niger and Penicillium chrysogenum, respectively. All
      influenced features were below m/z 600 (mass-to-charge ratio). We have observed
      silver ions and their clusters (Ag, Ag2, and Ag3) accumulated in the mould
      mycelium. As well as, mono-silver ion adducts with nucleotide derivatives
      (Coenzyme A), amino acids (phenylglycine), peptides (LeuSerAlaLeuGlu) and lipids
      (fatty acids, diacylglycerophosphoglycerols, monoglicerides and
      glycerophospholipids). The ultrastructure analysis revealed many sever
      alterations due to the action of AgNPs, such us shortening and condensation of
      hyphae, ultrastructural reorganisation, cell plasmolysis, increased
      vacuolisation, numerous membranous structures, collapsed cytoplasm, accumulation
      of lipid material, condensed mitochondria, disintegration of organelles, nuclear
      deformation, condensation and fragmentation of chromatin, creation of apoptotic
      bodies, as well as a new inside cell wall in P. chrysogenum.

PMID- 27896350
TI  - Characterizing the optical properties of single palladium-coated core-shell gold
      nanorods as multifunctional orientation probes.
AB  - Bimetallic core-shell gold nanorods are promising multifunctional orientation
      probes due to the synergetic effect of two different metals, as examined under an
      optical microscope. Herein, we performed a single particle study to characterize
      the optical properties of palladium-coated core-shell gold nanorods (Pd-AuNRs)
      using scattering-based dark-field (DF) and differential interference contrast
      (DIC) microscopy, and to examine their use as multifunctional orientation probes
      in biological and physical studies. The longitudinal surface plasmon resonance
      (SPR) was strongly damped with the increased SPR linewidth for single Pd-AuNRs
      due to Pd metals coated on the AuNR surface under single particle scattering
      spectroscopy. Despite the strong plasmon damping with much reduced scattering
      intensity, DIC microscopy allowed us to detect single Pd-AuNRs with much higher
      sensitivity. We found polarization-dependent DIC images and intensities of single
      Pd-AuNRs, which enabled the determination of their orientation angle under DIC
      microscopy. Furthermore, we found that DIC polarization anisotropy can be
      obtained from the orthogonally polarized bright and dark intensities for more
      accurate and reliable angle measurements of the Pd-AuNR probes. The results
      support the idea that bimetallic Pd-AuNRs can be used to develop multifunctional
      orientation probes.

PMID- 27896351
TI  - On-chip integration of organic synthesis and HPLC/MS analysis for monitoring
      stereoselective transformations at the micro-scale.
AB  - We present a microfluidic system, seamlessly integrating microflow and microbatch
      synthesis with a HPLC/nano-ESI-MS functionality on a single glass chip. The
      microfluidic approach allows to efficiently steer and dispense sample streams
      down to the nanoliter-range for studying reactions in quasi real-time. In a proof
      of-concept study, the system was applied to explore amino-catalyzed reactions,
      including asymmetric iminium-catalyzed Friedel-Crafts alkylations in microflow
      and micro confined reaction vessels.

PMID- 27896352
TI  - High-throughput metabolomics approach reveals new mechanistic insights for drug
      response of phenotypes of geniposide towards alcohol-induced liver injury by
      using liquid chromatography coupled to high resolution mass spectrometry.
AB  - Alcohol-induced liver injury (ALD) shows obvious metabolic disorders, categorized
      by a wide range of metabolite abnormalities. High-throughput metabolomics
      technology appears to be an appropriate solution. In this study, a urine
      metabolic profile was assessed using a UPLC-Q-TOF/HDMS (liquid chromatography
      coupled to high resolution mass spectrometry) approach to investigate the
      underlying molecular mechanisms of ALD and the therapeutic effect of geniposide.
      The endogenous low-molecular-weight metabolites in the mouse model of ALD were
      observed and 48 specific biomarkers were identified. Geniposide was found to have
      a regulatory effect on 32 of them. Furthermore, targeted analysis of biomarkers
      showed clear separation between the model and geniposide treatment group. Fifteen
      biomarkers with high contribution to group differentiation were screened out.
      Also, a comprehensive analysis of a significant disturbance of multiple metabolic
      pathways indicated that geniposide could modify abnormal metabolism due to
      ethanol exposure, during which disorders relating to amino acid metabolism and
      the oxidative stress state could be alleviated. At the same time, accessory
      examinations, including plasma biochemical indicators and liver tissue
      pathological analysis, showed similar results. It was suggested that geniposide
      was effective as a hepatoprotective agent against ethanol-induced liver damage by
      re-balancing a wide range of metabolic disorders.

PMID- 27896353
TI  - Pseudopeptidic compounds for the generation of dynamic combinatorial libraries of
      chemically diverse macrocycles in aqueous media.
AB  - A straightforward four-step synthesis leads to the preparation of C2-symmetric
      dithiols containing a central aromatic core and amino acid side chains. These
      building blocks allow the preparation of dynamic covalent libraries of
      pseudopeptidic macrocycles in aqueous media that cover a broad range of
      polarities, functional groups and bulkiness mirroring the diversity found in
      natural peptides. The versatility of the generated dynamic libraries has been
      illustrated by the amplification of two different members from the same library
      upon the action of two biologically relevant templates.

PMID- 27896354
TI  - Structural and dynamic studies of substrate binding in porous metal-organic
      frameworks.
AB  - Porous metal-organic frameworks (MOFs) are the subject of considerable research
      interest because of their high porosity and capability of specific binding to
      small molecules, thus underpinning a wide range of materials functions such as
      gas adsorption, separation, drug delivery, catalysis, and sensing. MOFs,
      constructed by the designed assembly of metal ions and functional organic
      linkers, are an emerging class of porous materials with extended porous
      structures containing periodic binding sites. MOFs thus provide a new platform
      for the study of the chemistry and reactivity of small molecules in confined
      pores using advanced diffraction and spectroscopic techniques. In this review, we
      focus on recent progress in experimental investigations on the crystallographic,
      dynamic and kinetic aspects of substrate binding within porous MOFs. In
      particular, we focus on studies on host-guest interactions involving open metal
      sites or pendant functional groups in the pore as the primary binding sites for
      guest molecules.

PMID- 27896355
TI  - Structural diversity and magnetic properties of six cobalt coordination polymers
      based on 2,2'-phosphinico-dibenzoate ligand.
AB  - Six novel Co(ii) coordination polymers, namely, [Co10L6(OH)2(H2O)9].10.5H2O (1),
      [Co3L2(3-abpt)2].4H2O (2), [Co3L2(4-azpy)2(H2O)2(EtOH)] (3), [Co3L2(4,4'
      bipy)2(H2O)2(MeCN)] (4), [Co3L2(4,4'-bipy)2] (5), and [Co5L2(OH)2(ina)2(H2O)2]
      (6) (H3L = 2,2'-phosphinico-dibenzoic acid, 3-abpt = 4-amino-3,5-bis(3-pyridyl)
      1,2,4-triazole, 4-azpy = 4,4'-azobispyridine, 4,4'-bipy = 4,4'-bipyridine, Hina =
      isonicotinic acid), have been hydrothermally synthesized and their magnetic
      properties have been characterized. The L3- anion displays six types of
      coordination modes in the compounds. Compound 1 exhibits a novel 1D ladder-like
      structure, which consists of non-centrosymmetric Co10 units. Compounds 2-4
      comprise 2D networks assembled from Co3L2 chains and N-heterocyclic linkers.
      Compound 5 comprises a 3D framework built from six neighboring parallel Co3L2
      ladders bridged by 4,4'-bipy linkers. Compound 6 features a 3D framework that
      exhibits pcu topology with the Schlafli symbol of (412.63) using a pentanuclear
      [Co5(OH)2]8+ cluster as the node. Variable-temperature magnetic susceptibility
      studies indicate that the six coordination polymers exhibit remarkable magnetic
      behavior such as spin-canted antiferromagnetism and spin glass, which were found
      to coexist in compound 6.

PMID- 27896356
TI  - Vapochromic features of new luminogens based on julolidine-containing styrene
      copolymers.
AB  - We report on vapochromic films suitable for detecting volatile organic compounds
      (VOCs), based on new polystyrene copolymers containing julolidine fluorescent
      molecular rotors (JCAEM). Poly(styrene-co-hydroxyethylmethacrylate) copolymers
      functionalized with cyanovinyl-julolidine moieties of different compositions were
      prepared, (P(STY-co-JCAEM)(m) with m = 0.06-0.61). The sensing performance of the
      spin-coated copolymer films demonstrated significant vapochromism when exposed to
      VOCs characterized by high vapour pressure and a favourable interaction with the
      polymer matrix, such as Et2O and CH2Cl2. It is worth mentioning that the
      fluorescence decrease rate was 7 times faster than that of previously
      investigated julolidine-based fluorescent molecular rotors dispersed in PS films.
      This phenomenon was attributed to the better control of the JCAEM moiety
      distribution in the polymer matrix conferred by the covalent approach, combined
      with a minimal film thickness of 4 microns. These factors, in concert, strongly
      accelerate the deactivation pathways of the JCAEM units in the presence of VOCs
      which interact well. Overall, the present results support the use of julolidine
      enriched styrene copolymers as effective chromogenic materials suitable for the
      fast detection of VOCs.

PMID- 27896357
TI  - Photoluminescence spectra and quantum yields of gold nanosphere monomers and
      dimers in aqueous suspension.
AB  - The intrinsic one-photon excited photoluminescence (PL) of dimers and monomers of
      gold spheres suspended in water was studied by combining photon time-of-flight
      spectroscopy (PTOFS) and light scattering fluctuation correlation spectroscopy
      (LS-FCS). The samples are obtained by precisely controlling the dimerization of
      aqueous colloidal systems based on 50 and 80 nm gold nanospheres. The combination
      of PTOFS and LS-FCS enables the separate spectroscopic study of monomers and
      dimers even though they exist as a mixture in the samples. PL emission spectra
      and diffusional dynamics are obtained simultaneously through measurement at the
      single particle level. The PL spectra resemble the light scattering spectra,
      indicating the plasmon-assisted character of the photoluminescence process. We
      determine the intrinsic PL quantum yields of the dimers and the monomers. It is
      often not possible to measure such very low quantum yields in solution using
      conventional techniques, and we show here that PTOFS provides access to this
      information. The quantum yield of the dimers was found to be of same order of
      magnitude as that of the monomers, of the order of 10-6, which indicates that the
      interparticle 'electromagnetic hot-spots' do not play a major role in the
      luminescence emission mechanism in such plasmonic molecules.

PMID- 27896358
TI  - Emergence of ordered network mesophases in kinetic pathways of order-order
      transition for linear ABC triblock terpolymers.
AB  - Applying the string method to the self-consistent field theory (SCFT) of ABC
      linear triblock copolymers, we developed a new strategy to design kinetic
      pathways for the formation of stable or metastable network mesophases in order
      order transition (OOT) processes. The design principle regarding the kinetic
      pathways between distinct mesophases is based on the matching relationships of
      both domain spacing and dominant Fourier components of the density distributions.
      The results suggest that complex ordered network mesophases, such as alternating
      diamond (DA) and alternating plumber's nightmare (PA) could be obtained in
      kinetic pathways between simple phases covering lamellae, cylinders and spheres.
      By virtue of the minimal free energy pathway (MEP) obtained, we could acquire the
      epitaxial relationship and phase transition mechanism. Furthermore, we managed to
      regulate the MEP by changing the block composition to adjust packing frustration.
      Two new metastable networks, core-shell five-pronged and six-pronged
      morphologies, were found in the kinetic pathways, further demonstrating the
      regulating mechanism. The results will contribute to a better understanding of
      the kinetic relationship between simple phases and complex networks, thus
      providing a platform for soft materials design via the OOT route and guiding
      experimental procedures to fabricate ordered network mesophases.

PMID- 27896359
TI  - Management of chronic hepatitis C in 2017.
AB  - Hepatitis C virus (HCV) represents one of the most common aetiologies of chronic
      liver disease and causes a major global health burden. Globally an estimated 80
      million people are chronically infected, but the majority of whom is still
      undiagnosed. Prior to the discovery of the virus in 1989 a significant number of
      patients were exposed and consecutively infected with HCV via contaminated
      transfusions, as it is a blood-borne disease. Chronic HCV infection pursues a
      progressive course that ultimately results in the development of cirrhosis, liver
      failure and hepatocellular carcinoma (HCC), if left untreated. The efficiency and
      tolerability of therapeutical approaches improved considerably with the
      development of direct-acting antivirals (DAA). The majority of patients treated
      with the recommended DAA combinations can be cured, which is reflected in
      achievement of sustained virological response (SVR). This review is intended to
      provide guidance in the management of patients with chronic hepatitis C,
      including recommendations for adequate screening, diagnostic procedures, clinical
      care, treatment and follow-up strategies.

PMID- 27896361
TI  - Intracranial Stenting in Germany : The Reimbursement Decision has been made, but
      the Scientific Debate Continues.

PMID- 27896360
TI  - Optical redox imaging indices discriminate human breast cancer from normal
      tissues.
AB  - Our long-term goal was to investigate the potential of incorporating redox
      imaging technique as a breast cancer (BC) diagnosis component to increase the
      positive predictive value of suspicious imaging finding and to reduce unnecessary
      biopsies and overdiagnosis. We previously found that precancer and cancer tissues
      in animal models displayed abnormal mitochondrial redox state. We also revealed
      abnormal mitochondrial redox state in cancerous specimens from three BC patients.
      Here, we extend our study to include biopsies of 16 patients. Tissue aliquots
      were collected from both apparently normal and cancerous tissues from the
      affected cancer-bearing breasts shortly after surgical resection. All specimens
      were snap-frozen and scanned with the Chance redox scanner, i.e., the three
      dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized
      flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous
      tissues roughly tripled that in the normal tissues ( p < 0.05 ). The redox ratio
      Fp/(NADH + Fp) was ? 27 % higher in the cancerous tissues ( p < 0.05 ).
      Additionally, Fp, or NADH, or the redox ratio alone could predict cancer with
      reasonable sensitivity and specificity. Our findings suggest that the optical
      redox imaging technique can provide parameters independent of clinical factors
      for discriminating cancer from noncancer breast tissues in human patients.

PMID- 27896362
TI  - The association between urinary sodium to potassium ratio and bone density in
      middle-aged Chinese adults.
AB  - : The joint effect of sodium and potassium on bone health remains uncertain. We
      examined the associations between urinary excretion of sodium, potassium, and
      their ratio and bone mineral density (BMD), and reported an inverse association
      between urinary sodium-to-potassium ratio and BMD in women, but not in men.
      INTRODUCTION: Several studies have suggested that a higher sodium or lower
      potassium intake is associated with poor bone health. However, few studies have
      examined their joint effects. We examined the associations of urinary excretion
      of sodium, potassium, and the sodium-to-potassium ratio with BMD in Chinese
      adults. METHODS: This community-based, cross-sectional study included 2202 women
      and 1063 men (40-75 years) in Guangzhou, China. The BMD of the whole body, lumbar
      spine, and hip sites were measured by dual-energy x-ray absorptiometry. The
      concentrations of sodium, potassium, and creatinine of the fasting morning first
      void urine sample were measured, and creatinine-adjusted values were then used
      for further analyses. General information was collected via face-to-face
      interviews. RESULTS: For women, after multivariable adjustment, the urinary
      sodium-to-potassium ratio was inversely associated with BMD at the whole body,
      total hip, trochanter, and intertrochanter (all p trend <0.05). The mean BMD
      differences between extreme quartiles ranged from 1.50 to 2.98 % at these sites
      (all p < 0.05). Similar, but less significant, associations were observed for
      urinary sodium/creatinine, for which the only significant difference was found at
      the trochanter (2.00 %, p = 0.016). We did not find any significant associations
      of BMD with urinary potassium in women and with urinary sodium/creatinine,
      potassium/creatinine, or their ratio in men. CONCLUSION: Our findings suggest
      that the urinary sodium-to-potassium ratio, but not individual creatinine
      adjusted values of sodium or potassium, is a good predictor of BMD in women, but
      not in men.

PMID- 27896364
TI  - [Proximal rupture of the hamstring tendon : From clinical presentation to
      diagnosis and therapy].
AB  - Rupture of the proximal tendon enthesis of the hamstring muscle (ICM) accounts
      for approximately 10% of all injuries of the ICM. It occurs most commonly in
      athletes and active middle-aged individuals. The complete rupture of all three
      tendons in active patients is generally seen as an indication for surgical repair
      of the tendon enthesis; however, the correct diagnosis is often not reached in a
      timely manner. This can lead to prolonged symptoms with pain, weakness and
      neuralgia. Operative treatment consists of anchor repair of the tendons resulting
      in good clinical outcome in several case series. Good knowledge of the anatomy
      and operative approach are mandatory to avoid complications as well as compliance
      with a gradual rehabilitation scheme to allow tendon to bone healing. The main
      aim of this review is to highlight the typical history, clinical presentation and
      examination technique to reach an immediate clinical diagnosis which should be
      confirmed with a magnetic resonance imaging (MRI) scan.

PMID- 27896363
TI  - Oxygen ultra-fine bubbles water administration prevents bone loss of
      glucocorticoid-induced osteoporosis in mice by suppressing osteoclast
      differentiation.
AB  - : Oxygen ultra-fine bubbles (OUB) saline injection prevents bone loss of
      glucocorti?coid-induced osteoporosis in mice, and OUB inhibit osteoclastogenesis
      via RANK-TRAF6-c-Fos-NFATc1 signaling and RANK-p38 MAPK signaling in vitro.
      INTRODUCTION: Ultra-fine bubbles (<200 nm in diameter) have several unique
      properties, and they are tested in various medical fields. The purpose of this
      study was to investigate the effects of oxygen ultra-fine bubbles (OUB) on
      glucocorticoid-induced osteoporosis (GIO) model mice. METHODS: Prednisolone (PSL,
      5 mg) was subcutaneously inserted in 6-month-old male C57BL/6J mice, and 200 MUl
      of saline, OUB-diluted saline, or nitrogen ultra-fine bubbles (NUB)-diluted
      saline was intraperitoneally injected three times per week for 8 weeks the day
      after operations. Mice were divided into four groups; (1) control, sham-operation
      + saline; (2) GIO, PSL + saline; (3) GIO + OUB, PSL + OUB saline; (4) GIO + NUB,
      PSL + NUB saline. The effects of OUB on osteoblasts and osteoclasts were examined
      by serially diluted OUB medium in vitro. RESULTS: Bone mass was significantly
      decreased in GIO [bone volume/total volume (%): control vs. GIO 12.6 vs. 7.9; p <
      0.01] while significantly preserved in GIO + OUB (GIO vs. GIO + OUB 7.9 vs. 12.9;
      p < 0.05). In addition, tartrate-resistant acid phosphatase (TRAP)-positive cells
      in the distal femur [mean osteoclasts number/bone surface (mm-1)] was
      significantly increased in GIO (control vs. GIO 6.8 vs. 11.6; p < 0.01) while
      suppressed in GIO + OUB (GIO vs. GIO + OUB 11.6 vs. 7.5; p < 0.01). NUB did not
      affect these parameters. In vitro experiments revealed that OUB significantly
      inhibited osteoclastogenesis by inhibiting RANK-TRAF6-c-Fos-NFATc1 signaling,
      RANK-p38 MAPK signaling, and TRAP/Cathepsin K/DC-STAMP mRNA expression in a
      concentration-dependent manner. OUB did not affect osteoblastogenesis in vitro.
      CONCLUSIONS: OUB prevent bone loss in GIO mice by inhibiting osteoclastogenesis.

PMID- 27896365
TI  - [Complete proximal hamstring tendon tear : Anchor-based sliding suture technique
      for reduction and fixation].

PMID- 27896366
TI  - Allelism analysis of BrRfp locus in different restorer lines and map-based
      cloning of a fertility restorer gene, BrRfp1, for pol CMS in Chinese cabbage
      (Brassica rapa L.).
AB  - KEY MESSAGE: In Chinese cabbage, there are two Rf loci for pol CMS and one of
      them was mapped to a 12.6-kb region containing a potential candidate gene
      encoding PPR protein. In Chinese cabbage (Brassica rapa), polima cytoplasmic male
      sterility (pol CMS) is an important CMS type and is widely used for hybrid
      breeding. By extensive test crossing in Chinese cabbage, four restorer lines
      (92s105, 01s325, 00s109, and 88s148) for pol CMS were screened. By analyzing the
      allelism of the four restorer lines, it was found that 92s105, 01s325, and 00s109
      had the same "restorers of fertility" (Rf) locus (designated as BrRfp1), but
      88s148 had a different Rf locus (designated as BrRfp2). For fine mapping the
      BrRfp1 locus of 92s105, a BC1F1 population with 487 individuals and a BC1F2
      population with 2485 individuals were successively constructed. Using simple
      sequence repeat (SSR) markers developed from Brassica rapa reference genome and
      InDel markers derived from whole-genome resequencing data of 94c9 and 92s105,
      BrRfp1 was mapped to a 12.6-kb region containing a potential candidate gene
      encoding pentatricopeptide repeat-containing protein. Based on the nucleotide
      polymorphisms of the candidate gene sequence between the restoring and
      nonrestoring alleles, a co-segregating marker SC718 was developed, which would be
      helpful for hybrid breeding by marker-assisted screening and for detecting new
      restorer lines.

PMID- 27896367
TI  - Erratum to: Fine mapping and candidate gene analysis of qHD5, a novel major QTL
      with pleiotropism for yield-related traits in rice (Oryza sativa L.).

PMID- 27896368
TI  - Targeting of the WT191-138 fragment to human dendritic cells improves leukemia
      specific T-cell responses providing an alternative approach to WT1-based
      vaccination.
AB  - Due to its immunogenicity and overexpression concomitant with leukemia
      progression, Wilms tumor protein 1 (WT1) is of particular interest for
      immunotherapy of AML relapse after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly
      been induced by vaccination with peptides presented by certain HLA alleles.
      However, this approach is still not widely applicable in clinical practice due to
      common limitations of HLA restriction. Dendritic cell (DC) vaccines
      electroporated with mRNA encoding full-length protein have also been tested for
      generating WT1-derived peptides for presentation to T-cells. Alternatively, an
      efficient and broad WT1 peptide presentation could be elicited by triggering
      receptor-mediated protein endocytosis of DCs. Therefore, we developed antibody
      fusion proteins consisting of an antibody specific for the DEC205 endocytic
      receptor on human DCs and various fragments of WT1 as DC-targeting recombinant
      WT1 vaccines (anti-hDEC205-WT1). Of all anti-hDEC205-WT1 fusion proteins designed
      for overcoming insufficient expression, anti-hDEC205-WT110-35, anti-hDEC205-WT191
      138, anti-hDEC205-WT1223-273, and anti-hDEC205-WT1324-371 were identified in good
      yields. The anti-hDEC205-WT191-138 was capable of directly inducing ex vivo T
      cell responses by co-incubation of the fusion protein-loaded monocyte-derived
      mature DCs and autologous T-cells of either healthy or HSCT individuals.
      Furthermore, the DC-targeted WT191-138-induced specific T-cells showed a strong
      cytotoxic activity by lysing WT1-overexpressing THP-1 leukemia cells in vitro
      while sparing WT1-negative hematopoietic cells. In conclusion, our approach
      identifies four WT1 peptide-antibody fusion proteins with sufficient production
      and introduces an alternative vaccine that could be easily translated into
      clinical practice to improve WT1-directed antileukemia immune responses after
      allo-HSCT.

PMID- 27896371
TI  - [Mental treatment of refugees in Germany : Model for a stepped approach].
AB  - The recent influx of refugees and asylum seekers into Germany poses a challenge
      for the national healthcare system. In compliance with the present Asylum Seekers
      Benefits Act, the national healthcare system can be expected to have 1.5 million
      new members by early 2017. Providing adequate care particularly for people with
      mental illnesses or disorders will represent an immense challenge for all actors
      in the system. The circumstances of the flight combined with the foreign
      linguistic and socio-cultural background increase the severity of the cases and
      the difficulties of treatment. No procedures or guidelines for treatment have yet
      been established to ensure a standardized, cost-efficient and therapeutically
      effective treatment of patients with this background. This article describes the
      components of a stepped treatment procedure and proposes a stepped and
      collaborative care model (SCCM) that could be evaluated in nationwide studies.
      This approach is based on national and international treatment guidelines and
      aims to provide target-group specific, culturally sensitive methods of diagnosis
      and treatment. The various steps of the model build on each other, with the first
      steps relying on technological aids (e.g. online or smartphone options) and
      support from lay helpers and the more expensive specialist psychiatric and
      psychotherapeutic therapy only being initiated in cases of more severe mental
      disorders.

PMID- 27896369
TI  - Detection rate of PET/CT in patients with biochemical relapse of prostate cancer
      using [68Ga]PSMA I&T and comparison with published data of [68Ga]PSMA HBED-CC.
AB  - PURPOSE: To determine the detection rate of PET/CT in biochemical relapse of
      prostate cancer using [68Ga]PSMA I&T and to compare it with published detection
      rates of [68Ga]PSMA HBED-CC. METHODS: We performed a retrospective analysis in 83
      consecutive patients with documented biochemical relapse after prostatectomy. All
      patients underwent whole body [68Ga]PSMA I&T PET/CT. PET/CT images were evaluated
      for presence of local recurrence, lymph node metastases, and distant metastases.
      Proportions of positive PET/CT results were calculated for six subgroups with
      increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL,
      1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, >=10.0 ng/mL). Detection
      rates of [68Ga]PSMA I&T were statistically compared with published detection
      rates of [68Ga]PSMA HBED-CC using exact Fisher's test. RESULTS: Median PSA was
      0.81 (range: 0.01 - 128) ng/mL. In 58/83 patients (70 %) at least one [68Ga]PSMA
      I&T positive lesion was detected. Local recurrent cancer was present in 18
      patients (22 %), lymph node metastases in 29 patients (35 %), and distant
      metastases in 15 patients (18 %). The tumor detection rate was positively
      correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55
      % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 %
      (5.0 to <10.0 ng/mL), and 100 % (>=10.0 ng/mL). There was no significant
      difference between the detection rate of [68Ga]PSMA I&T and published detection
      rates of [68Ga]PSMA HBED-CC (all p>0.05). CONCLUSIONS: [68Ga]PSMA I&T PET/CT has
      high detection rates of recurrent prostate cancer that are comparable to
      [68Ga]PSMA HBED-CC.

PMID- 27896372
TI  - Opioid receptor agonists may favorably affect bone mechanical properties in rats
      with estrogen deficiency-induced osteoporosis.
AB  - The results of epidemiological, clinical, and in vivo and in vitro experimental
      studies on the effect of opioid analgesics on bone are inconsistent. The aim of
      the present study was to investigate the effect of morphine (an agonist of opioid
      receptors), buprenorphine (a partial MU opioid receptor agonist and kappa opioid
      receptor antagonist), and naloxone (an antagonist of opioid receptors) on the
      skeletal system of female rats in vivo. The experiments were carried out on 3
      month-old Wistar rats, divided into two groups: nonovariectomized (intact; NOVX)
      rats and ovariectomized (OVX) rats. The bilateral ovariectomy was performed 7
      days before the start of drug administration. Morphine hydrochloride (20
      mg/kg/day s.c.), buprenorphine (0.05 mg/kg/day s.c.), or naloxone hydrochloride
      dihydrate (2 mg/kg/day s.c.) were administered for 4 weeks to NOVX and OVX rats.
      In OVX rats, the use of morphine and buprenorphine counteracted the development
      of osteoporotic changes in the skeletal system induced by estrogen deficiency.
      Morphine and buprenorphine beneficially affected also the skeletal system of NOVX
      rats, but the effects were much weaker than those in OVX rats. Naloxone generally
      did not affect the rat skeletal system. The results confirmed the role of opioid
      receptors in the regulation of bone remodeling processes and demonstrated, in
      experimental conditions, that the use of opioid analgesics at moderate doses may
      exert beneficial effects on the skeletal system, especially in estrogen
      deficiency.

PMID- 27896374
TI  - Loss of group memberships predicts depression in postpartum mothers.
AB  - PURPOSE: The postpartum period presents the highest risk for women's mental
      health throughout the lifespan. We aimed to examine the Social Identity Model of
      Identity Change in this context. More specifically, we investigated changes in
      social identity during this life transition and their consequences for women's
      postpartum mental health. METHODS: Women who had given birth within the last 12
      months (N = 387) reported on measures of depression, social group memberships,
      and motherhood identification. RESULTS: Analyses indicated that a decrease in
      group memberships after having a baby, controlling for group memberships prior to
      birth, was associated with an increase in depressive symptomology. However,
      maintaining pre-existing group memberships was predictive of better mental
      health. New group memberships were not associated with depressive symptomology.
      Identification as a mother was a strong positive predictor of mental health in
      the postpartum period. CONCLUSIONS: The social identity model of identity change
      provides a useful framework for understanding postpartum depression.
      Interventions to prevent and treat postpartum depression might aim to support
      women in maintaining important social group networks throughout pregnancy and the
      postpartum period.

PMID- 27896373
TI  - Assessing colonic anatomy normal values based on air contrast enemas in children
      younger than 6 years.
AB  - BACKGROUND: Contrast enemas with barium or water-soluble contrast agents are
      sometimes performed in children with severe intractable constipation to identify
      anatomical abnormalities. However there are no clear definitions for normal
      colonic size or abnormalities such as colonic dilation or sigmoid redundancy in
      children. OBJECTIVE: To describe characteristics of colonic anatomy on air
      contrast enemas in children without constipation to provide normal values for
      colonic size ratios in children. MATERIALS AND METHODS: We performed a
      retrospective chart review of children aged 0-5 years who had undergone air
      contrast enemas for intussusception. The primary outcome measures were the ratios
      of the diameters and lengths of predetermined colonic segments (lengths of
      rectosigmoid and descending colon; diameters of rectum, sigmoid, descending
      colon, transverse colon and ascending colon) in relation to the L2 vertebral body
      width. RESULTS: We included 119 children (median age 2.0 years, range 0-5 years,
      68% boys). Colonic segment length ratios did not change significantly with age,
      although the differences for the rectosigmoid/L2 ratio were borderline
      significant (P = 0.05). The ratios that involved the rectal and ascending colon
      diameters increased significantly with age, while diameter ratios involving the
      other colonic segments did not. Differences by gender and race were not
      significant. CONCLUSION: These data can be used for reference purposes in young
      children undergoing contrast studies of the colon.

PMID- 27896375
TI  - [Extracorporeal CO2 removal as an alternative to tracheotomy in a patient with
      extubation failure].
AB  - We report a patient with chest trauma who was admitted to the ICU after surgery.
      As he fulfilled protocol-based criteria, he was extubated 7 days after admission.
      However, despite intermittent non-invasive ventilation, the patient had to be re
      intubated on day 10 owing to progressive hypercapnia. We decided to support the
      patient with a mid-flow veno-venous extracorporeal carbon dioxide removal (ECCO2
      R) system instead of a tracheotomy. Sufficient CO2 removal was established with a
      blood flow of 1.5 l/min and the patient was successfully extubated within a few
      hours. After 5 days of ECCO2-R the patient could be weaned and transferred to a
      general ward in a stable condition.

PMID- 27896376
TI  - Reducing the Bottleneck in Discovery of Novel Antibiotics.
AB  - Most antibiotics were discovered by screening soil actinomycetes, but the
      efficiency of the discovery platform collapsed in the 1960s. By now, more than
      3000 antibiotics have been described and most of the current discovery effort is
      focused on the rediscovery of known compounds, making the approach impractical.
      The last marketed broad-spectrum antibiotics discovered were daptomycin,
      linezolid, and fidaxomicin. The current state of the art in the development of
      new anti-infectives is a non-existent pipeline in the absence of a discovery
      platform. This is particularly troubling given the emergence of pan-resistant
      pathogens. The current practice in dealing with the problem of the background of
      known compounds is to use chemical dereplication of extracts to assess the
      relative novelty of a compound it contains. Dereplication typically requires
      scale-up, extraction, and often fractionation before an accurate mass and
      structure can be produced by MS analysis in combination with 2D NMR. Here, we
      describe a transcriptome analysis approach using RNA sequencing (RNASeq) to
      identify promising novel antimicrobial compounds from microbial extracts. Our
      pipeline permits identification of antimicrobial compounds that produce distinct
      transcription profiles using unfractionated cell extracts. This efficient
      pipeline will eliminate the requirement for purification and structure
      determination of compounds from extracts and will facilitate high-throughput
      screen of cell extracts for identification of novel compounds.

PMID- 27896377
TI  - Self-administration and behavioral economics of second-generation synthetic
      cathinones in male rats.
AB  - RATIONALE: Synthetic cathinones have become increasingly available as drugs of
      abuse. Distribution of these drugs is made possible by altering the chemical
      structures of prohibited cathinones and marketing them under misleading labels.
      Very little is known about the relative reinforcing effectiveness of new
      synthetic cathinones relative to known drugs of abuse. OBJECTIVE: We examined
      self-administration of three second-generation synthetic cathinones: alpha
      pyrrolidinopentiophenone (alpha-PVP), 4-methyl-N-ethylcathinone (4-MEC), and 4
      methyl-alpha-pyrrolidinopropiophenone (4-MePPP) relative to methamphetamine.
      METHOD: Male, Sprague-Dawley rats, implanted with intravenous catheters, were
      trained to self-administer methamphetamine (0.05 mg/kg/injection) under a fixed
      ratio schedule. Following training, various doses of methamphetamine (0.006-0.1
      mg/kg/injection), alpha-PVP (0.0015-0.1 mg/kg/injection), 4-MEC (0.1-3.2
      mg/kg/injection), or 4-MePPP (0.1-0.8 mg/kg/injection) were available for self
      administration in separate groups, followed by a behavioral-economics evaluation
      of the reinforcing effectiveness of each drug. RESULTS: For all drugs, at least
      one dose functioned as a reinforcer. Alpha-PVP and 4-MePPP maintained the highest
      numbers of infusions per session and both were more effective reinforcers
      relative to methamphetamine. 4-MEC and methamphetamine were not significantly
      different in terms of infusions per session or reinforcing effectiveness.
      CONCLUSION: Emerging synthetic cathinones whose primary pharmacological mechanism
      is to block dopamine uptake but with little effects on monoamine release or
      serotonin uptake may have a greater degree of abuse potential compared with known
      abused stimulants.

PMID- 27896378
TI  - Reply to: kynurenic acid and alcohol and cocaine dependence: novel effects and
      multiple mechanisms?

PMID- 27896379
TI  - Seizure and tetany secondary to hypomagnesaemic hypoparathyroidism induced by a
      proton-pump inhibitor.

PMID- 27896381
TI  - CPR and brain death: confounders, clearance, caution.

PMID- 27896380
TI  - Authors' response: CPR and brain death: confounders, clearance, caution.

PMID- 27896382
TI  - The mechanism of improved intracellular organic selenium and glutathione contents
      in selenium-enriched Candida utilis by acid stress.
AB  - Batch culture of Candida utilis CCTCC M 209298 for the preparation of selenium
      (Se)-enriched yeast was carried out under different pH conditions, and maximal
      intracellular organic Se and glutathione (GSH) contents were obtained in a
      moderate acid stress environment (pH 3.5). In order to elucidate the
      physiological mechanism of improved performance of Se-enriched yeast by acid
      stress, assays of the key enzymes involved in GSH biosynthesis and determinations
      of energy supply and regeneration were performed. The results indicated that
      moderate acid stress increased the activity of gamma-glutamylcysteine synthetase
      and the ratios of NADH/NAD+ and ATP/ADP, although no significant changes in
      intracellular pH were observed. In addition, the molecular mechanism of moderate
      acid stress favoring the improvement of Se-yeast performance was revealed by
      comparing whole transcriptomes of yeast cells cultured at pH 3.5 and 5.5.
      Comparative analysis of RNA-Seq data indicated that 882 genes were significantly
      up-regulated by moderate acid stress. Functional annotation of the up-regulated
      genes based on gene ontology and the Kyoto Encyclopedia of Genes and Genome
      (KEGG) pathway showed that these genes are involved in ATP synthesis and sulfur
      metabolism, including the biosynthesis of methionine, cysteine, and GSH in yeast
      cells. Increased intracellular ATP supply and more amounts of sulfur-containing
      substances in turn contributed to Na2SeO3 assimilation and biotransformation,
      which ultimately improved the performance of the Se-enriched C. utilis.

PMID- 27896383
TI  - Degradation of Mesotrione Affected by Environmental Conditions.
AB  - With the widespread use of mesotrione, its residues have become increasingly
      serious and caused a series of environmental problems in northern China. To
      reduce the harm of these residues, we investigated the degradation effect of
      mesotrione in typical soils in northern China at different temperatures, soil
      moisture, pH values and initial concentrations. We also examined the influence of
      soil type, microorganisms and the use of organic matter and biogas slurry as soil
      amendments. Mesotrione degradation rates increased as the temperature, soil
      moisture, soil pH and the content of biogas slurry increased; and decreased as
      the organic content and the initial concentration of mesotrione increased. The
      degradation rates were different in the three soils. Microorganisms played an
      important role in the degradation process. These result may offer a theoretical
      basis for decreasing mesotrione residue when using this product in northern
      China.

PMID- 27896384
TI  - Uptake of Total Petroleum Hydrocarbon (TPH) and Polycyclic Aromatic Hydrocarbons
      (PAHs) by Oryza sativa L. Grown in Soil Contaminated with Crude Oil.
AB  - The purpose of this study was to determine whether total petroleum hydrocarbon
      (TPH) and polycyclic aromatic hydrocarbons (PAHs) present in crude oil
      contaminated sites are transferred to roots, shoots and finally the grains of
      rice crops (Oryza sativa L.) grown in those sites. Soil was artificially
      contaminated with crude oil at concentrations of 0, 1000, 5000, 10,000, and
      15,000 mg/kg, followed by planting of rice seedlings. After harvest, TPH in plant
      samples were measured, and it was determined that the uptake of TPH by the plants
      gradually increased as the concentration of oil in soil increased. Further, from
      GC-MS analysis, it was observed that PAHs including naphthalene and phenanthrene
      bioaccumulated in rice plant parts. Vital physico-chemical properties of soil
      were also altered due to crude oil contamination. Our study revealed that rice
      plants grown in crude oil polluted sites can uptake TPH including PAHs, thus
      emphasising the importance of prior investigation of soil condition before
      cultivation of crops.

PMID- 27896385
TI  - Pictorial review: the pearls and pitfalls of the radiological manifestations of
      gallstone ileus.
AB  - We present a pictorial review of a range of typical and atypical cases of
      gallstone ileus (GI), across a wide range of imaging modalities. GI is a
      complication of gallstone disease causing mechanical intestinal obstruction due
      to impaction of gallstone in the gastrointestinal tract. The spectrum of
      presentation can vary enormously, and we highlight the importance of accurate
      imaging diagnosis of GI especially early use of computed tomography. This will
      lead to timely and appropriate surgical intervention with the potential avoidance
      of unnecessary outcomes. The ambition of pictorial synopsis is to make the
      radiologists to be more vigilant to the common and more obscure imaging findings
      of GI.

PMID- 27896386
TI  - Dual energy CT angiography: pros and cons of dual-energy metal artifact reduction
      algorithm in patients after endovascular aortic repair.
AB  - PURPOSE: To evaluate the value of metal artifact reduction (MAR) post-processing
      and iodine MD images in fast kV-switching dual-energy computed tomography (DECT)
      in patients after endovascular aortic repair (EVAR). MATERIALS AND METHODS:
      Twenty-four consecutive EVAR patients (age 76 +/- 9 years, 7/24 (29%) with coils,
      9/24 (37.5%) with 10 endoleaks) who underwent DECT angiography were included in
      this HIPAA-compliant, IRB-approved retrospective study. Monochromatic
      reconstructions included 55, 60, 65, 70, and 75 keV with and without MAR and
      iodine MD images. Near field, far field, and vessel artifacts were assessed
      subjectively (1 = none; 5 = severe) and objectively by measuring noise and
      contrast-to-noise ratio. Visibility of endoleak was evaluated (1 = optimal; 5 =
      not visible). RESULTS: MAR objectively decreased artifacts from EVAR stents in
      the near field (60.7 +/- 25.4 HU vs. 70.1 +/- 34.2; p = .002) and subjectively
      increased near field (3.2 +/- 0.9 vs. 2.8 +/- 0.6; p < .001), far field (2.2 +/-
      0.6 vs. 1.6 +/- 0.6; p < .001), and vessel (3.1 +/- 1.1 vs. 2.5 +/- 0.9; p <
      .001) artifacts. Near-field artifacts from coils were reduced by the MAR
      objectively (72.4 +/- 24.8 vs. 182.7 +/- 57.3 HU; p < .001) and subjectively (4.5
      +/- 0.5 vs. 4.9 +/- 0.4; p = .02). CNR of standard reconstructions was optimal at
      60 keV (38.3 +/- 16.8). Reconstructions without MAR and iodine MD images provided
      improved endoleak visualization in 6/10 (60%) of cases (median 1 for both)
      compared to MAR (median 3) (p < 0.001). However, MAR improved visualization in
      1/10 (10%) cases due to endoleak location adjacent to a coil. CONCLUSION: DECT
      with MAR reduced artifacts from coils and improved endoleak visualization in 1/10
      (10%) cases due to location adjacent to a coil. However, MAR impaired endoleak
      visualization in 6/10 (60%) cases and should be reviewed combined with 60 keV
      standard reconstructions and iodine MD images.

PMID- 27896387
TI  - Alexandr I. Oparin and the Origin of Life: A Historical Reassessment of the
      Heterotrophic Theory.
AB  - The heterotrophic origin of life proposed by A. I. Oparin in the 1920s was part
      of a Darwinian framework that assumed that living organisms were the historical
      outcome of a gradual transformation of lifeless matter. Eighty years ago, he
      presented a much more detailed scheme of the processes that may have led to life.
      As argued here, the development of the heterotrophic theory has been shaped by an
      entangled scenario in which a number of technical and scientific developments
      concur, as well as non-scientific issues including the Stalinist period and the
      tensions of the Cold War atmosphere. What has been largely ignored until now is
      the key role played by Haeckel's ideas in shaping Oparin's theory. The
      heterotrophic theory has been erroneously described as a metabolism-first
      hypothesis in which genetic material was not included due to ideological
      pressures of the Soviet government. As shown here, both characterizations are
      mistaken. The development of Oparin's views and the ensuing debates cannot be
      understood without considering the confrontation between Mendelism and Darwinism
      during the first three decades of the past century, combined with the doubts
      surrounding the existence of genes.

PMID- 27896388
TI  - [Dying and death in societal transformation].
AB  - Dying and death in modern societies are subject to profound social, professional
      and cultural-religious changes. Secularization and a stronger differentiation of
      societies have led to a change in the way humans handle the dying process.
      Normatively ritualized collective behaviour has been replaced by an individual,
      subjectivized approach. In late modern societies there are many different views
      of what "successful" or "good" dying means.In the article this change is
      described by the following seven theses: 1. We live longer and we die longer. 2.
      We no longer die suddenly and unexpectedly but slowly and foreseeably. 3. Even
      though our biological life on earth has become longer, our life has been
      shortened by the loss of eternity. 4. We no longer die on the stage of ritualized
      relationships with our family and neighbours but behind the curtains of
      organizations. 5. We live and die in a society of organizations and have to get
      organized for the final phase of our life. 6. Living and dying are no large,
      state-owned enterprises but small, private enterprises. 7. The hospice movement
      as well as palliative medicine have created public awareness, made dying a matter
      of discussion and offered a new set of options.In late modernism end-of-life care
      requires new approaches based on individual and shared responsibility as well as
      cooperation between professional institutions and community-based voluntary
      care.A change towards community care is visible. Thus "dying" is a topic in the
      discussion about the future of public health and societal solidarity.

PMID- 27896389
TI  - [Attitudes and experiences regarding physician assisted suicide : A survey among
      members of the German Association for Palliative Medicine].
AB  - BACKGROUND: The need to regulate physician-assisted suicide (PAS) and
      organizations offering assisted suicide has been controversially debated in
      Germany. Before the German parliament voted on various drafts in November 2015,
      the German Association for Palliative Medicine surveyed its members on their
      attitudes and experiences regarding PAS. METHOD: Items for the survey were
      derived from the literature and consented in a focus group. LITERATURE SEARCH:
      2005-2015 - PubMed: PAS [Title/Abstract] UND survey (all countries), grey
      literature. We invited 5152 members of the DGP to participate in the online/paper
      survey. Descriptive quantitative and content analytic qualitative analysis of
      data using SPSS and MaxQDA. RESULTS: We obtained 1811 valid data sets (response
      rate 36.9%). 33.7% of the participants were male, 43.6% were female, and 0.4%
      identifed as other. Physicians accounted for 48.5% of the respondents, 17.8%
      nurses, other professions 14.3%, and about 20% of the data was missing socio
      demographic information. More than 90% agreed that "wishes for PAS may be
      ambivalent" and "are rather a wish to end an unbearable situation". Of the 833
      participating physicians, 56% refused participating in PAS and 74.2% had been
      asked to perform PAS. PAS was actually performed by 3%. Of all participating
      members, 56% approved of a legal ban of organizations offering assisted suicide.
      More than 60% of all professions agreed that PAS is not a part of palliative
      care. CONCLUSION: The respondents show a broad spectrum of attitudes, only partly
      supporting statements of relevant bodies, such as DGP. Because many are
      confronted with the issue, PAS is relevant to professionals in palliative care.

PMID- 27896390
TI  - [Assisted suicide in the movies - what is (not) shown?]
AB  - Whereas changes to the existing legal situation regarding assisted suicide have
      been a topic of controversial debate in Germany for the last few years, this
      issue has long been of interest for international film-makers. Since the mid
      1980s, the theme of assisted suicide has repeatedly been taken up by cinema,
      predominantly as central to a relationship drama. A sick person asks somebody
      close to them for help. Often this somebody is a physician or a nurse, ultimately
      an obvious way of solving the practical problem of how the assistant is to gain
      access to a lethal substance. At the same time, this constellation enables a
      physician or nurse to be forced into a dramatic conflict between professional
      ethics and a personal obligation towards a loved one.Alongside more classic
      clinical pictures such as terminal cancer, recent films about assisted suicide
      have featured neurodegenerative diseases and physical disabilities. Another new
      development is that elderly patients are no longer alone in requesting
      assistance; films also and increasingly portray young adults. Besides a fear of
      unbearable pain, more recent films have also increasingly addressed the worry
      that permanent nursing might be required, as well as the subjectively experienced
      loss of dignity. The possibilities offered by palliative care hardly play a role
      in feature films. However, we should not forget, that movies are fictional and
      orchestrated, or, in other words, they are neither educational nor documental.
      They neither need nor want to portray reality, although they do wish to draw upon
      real experiences. They exploit highly emotional and ethically controversial
      themes to create tensions and stir up emotions in the audience, but ultimately
      they seek to entertain. Movies about death and dying are always "die-tainment".

PMID- 27896392
TI  - Tubular and genetic disorders associated with kidney stones.
AB  - This concise review summarizes our current understanding and the recent
      developments in genetics and related renal tubular disorders that have been
      linked with, or have been shown to be causal in, renal stone disease. The aim is
      to provide a readily accessible quick and easy update for urologists,
      nephrologists and endocrine or metabolic physicians whose practice involves the
      diagnosis and management of nephrolithiasis. An important message is to always
      consider a seemingly rare, and usually genetic, cause of kidney stones, since
      some of these are emerging as more common than originally thought, especially in
      adult clinical practice in which a family history of stones is a common finding.

PMID- 27896391
TI  - Histological aspects of the "fixed-particle" model of stone formation: animal
      studies.
AB  - Crystallization by itself is not harmful as long as the crystals are not retained
      in the kidneys and are allowed to pass freely down the renal tubules to be
      excreted in the urine. A number of theories have been proposed, and studies
      performed, to determine the mechanisms involved in crystal retention within the
      kidneys. It has been suggested that urinary transit through the nephron is too
      fast for crystals to grow large enough to be retained. Thus, free particle
      mechanism alone cannot lead to stone formation, and there must be a mechanism for
      crystal fixation within the kidneys. Animal model studies suggest that crystal
      retention is possible through both the free- and fixed-particle mechanisms.
      Crystal-cell interaction leads to pathological changes which promote crystal
      attachment to either epithelial cells or their basement membrane. Alternatively,
      crystals aggregate and produce large enough particles to block the tubules
      particularly at sites, where urinary flow is affected because of changes in the
      luminal diameter of the tubule. Crystal deposits plugging the openings of the
      ducts of Bellini may be the result of such a phenomenon. Intratubular crystals
      translocating to renal interstitium may produce osteogenic changes in the
      epithelial or endothelial cells resulting in the formation of the Randall's
      plaques. Thus, fixation appears to be either through the formation of Randall's
      plugs, crystal plugs clogging the openings of the ducts of Bellini or sub
      epithelial crystal deposits, and the Randall's plaques.

PMID- 27896393
TI  - Degree of tendon degeneration and stage of rotator cuff disease.
AB  - PURPOSE: While tendon degeneration has been known to be an important cause of
      rotator cuff disease, few studies have objectively proven the association of
      tendon degeneration and rotator cuff disease. The purpose of this study was to
      investigate changes of tendon degeneration with respect to the stage of rotator
      cuff disease. METHODS: A total of 48 patients were included in the study: 12 with
      tendinopathy, 12 with a partial-thickness tear (pRCT), 12 with a full-thickness
      tear (fRCT), and 12 as the control. A full-thickness supraspinatus tendon sample
      was harvested en bloc from the middle portion between the lateral edge and the
      musculotendinous junction of the tendon using a biopsy punch with a diameter of 3
      mm. Harvested samples were evaluated using a semi-quantitative grading scale with
      7 parameters after haematoxylin and eosin staining. RESULTS: There was no
      significant difference in age, gender, symptom duration, and Kellgren-Lawrence
      grade between the groups except for the global fatty degeneration index. All of
      the seven parameters were significantly different between the groups and could be
      categorized as follows: early responders (fibre structure and arrangement),
      gradual responder (rounding of the nuclei), after-tear responders (cellularity,
      vascularity, and stainability), and late responder (hyalinization). The total
      degeneration scores were not significantly different between the control (6.08 +/
      1.16) and tendinopathy (6.67 +/- 1.83) (n.s.). However, the score of pRCT group
      (10.42 +/- 1.31) was greater than that of tendinopathy (P < 0.001), and so was
      the score of fRCT (12.33 +/- 1.15) than that of pRCT (p = 0.009). CONCLUSION:
      This study showed that the degeneration of supraspinatus tendon increases as the
      stage of rotator cuff disease progresses from tendinopathy to pRCT, and then to
      fRCT. The degree of degeneration of tendinopathy was not different from that of
      normal but aged tendons, and significant tendon degeneration began from the stage
      of pRCT. The clinical relevance of the study is that strategies and goals of the
      treatment for rotator cuff disease should be specific to its stage, in order to
      prevent disease progression for tendinopathy and pRCT, as well to restore the
      structural integrity for fRCT. LEVEL OF EVIDENCE: Diagnostic, Level I.

PMID- 27896394
TI  - The orientation of the surgical epicondylar axis varies in varus and non-varus
      knees in the coronal plane.
AB  - PURPOSE: To investigate the orientations of the surgical epicondylar axis (SEA)
      of varus and non-varus knees in the coronal plane. METHODS: One-hundred and sixty
      two knees from 81 Chinese patients undergoing total knee arthroplasty (TKA) were
      retrospectively investigated. The angle between the medial side of the femoral
      mechanical axis and the SEA (MA-SEA), as well as the physiological valgus angle,
      was measured in the coronal plane using three-dimensional reconstruction. The
      joint line angle (JLA) and hip-knee-ankle angle (HKAA) were measured in long-leg
      weight-bearing radiographs. The mean of each parameter was compared between the
      varus (HKAA < 177.0 degrees ) and the non-varus knees (HKAA >= 177.0 degrees )
      using an independent t test. Linear regression was used to assess the correlation
      between MA-SEA with JLA and HKAA. RESULTS: A total of 42 non-varus knees (6
      valgus and 36 neutral knees) and 98 varus knees were measured, as 22 knees were
      abandoned due to unrecognizable bony landmarks. The mean MA-SEA and JLA were
      significantly larger in non-varus knees (both, p < 0.01). The mean physiological
      valgus angle was 5.9 +/- 1.0 degrees  for Chinese TKA patients and was
      significantly larger in varus knees (p < 0.01). There was a strong positive
      correlation between the MA-SEA and JLA (R 2 = 0.35, p < 0.05). CONCLUSIONS: There
      were significant differences in the orientation of the SEA between varus and non
      varus knees, which was strongly correlated with the orientation of the femoral
      joint line. These findings will enhance the current knowledge of knee anatomy and
      should prove useful for coronal alignment in TKA. LEVEL OF EVIDENCE: III.

PMID- 27896397
TI  - Potential of vis-NIR spectroscopy to monitor the silica precipitation reaction.
AB  - Controlling production online is an important issue for chemical companies.
      Visible and near-infrared (NIR) spectroscopy offers a number of important
      advantages for process monitoring, and has been used since the 1980s. For complex
      media such as silica precipitation samples, it is interesting to be able to study
      independently the scattering and absorption effects. From the scattering
      coefficient it is possible to extract information on the physical structure of
      the medium. In this work, the physical changes were monitored during a silica
      precipitation reaction by simple measurement of collimated transmittance NIR
      spectra. It is shown that it is possible to differentiate samples before and
      after the gel point, which is a key parameter for monitoring the process. From
      these NIR spectra the scattering coefficients were simply extracted, allowing a
      global vision of the physical changes in the medium. Then principal component
      analysis of the spectra allowed refinement of the understanding of the scattering
      effects, in combination with particle size monitoring.

PMID- 27896396
TI  - Metabolic profiling of ob/ob mouse fatty liver using HR-MAS 1H-NMR combined with
      gene expression analysis reveals alterations in betaine metabolism and the
      transsulfuration pathway.
AB  - Metabolic perturbations resulting from excessive hepatic fat accumulation are
      poorly understood. Thus, in this study, leptin-deficient ob/ob mice, a mouse
      model of fatty liver disease, were used to investigate metabolic alterations in
      more detail. Metabolites were quantified in intact liver tissues of ob/ob (n = 8)
      and control (n = 8) mice using high-resolution magic angle spinning (HR-MAS) 1H
      NMR. In addition, after demonstrating that HR-MAS 1H-NMR does not affect RNA
      integrity, transcriptional changes were measured by quantitative real-time PCR on
      RNA extracted from the same specimens after HR-MAS 1H-NMR measurements.
      Importantly, the gene expression changes obtained agreed with those observed by
      Affymetrix microarray analysis performed on RNA isolated directly from fresh
      frozen tissue. In total, 40 metabolites could be assigned in the spectra and
      subsequently quantified. Quantification of lactate was also possible after
      applying a lactate-editing pulse sequence that suppresses the lipid signal, which
      superimposes the lactate methyl resonance at 1.3 ppm. Significant differences
      were detected for creatinine, glutamate, glycine, glycolate, trimethylamine-N
      oxide, dimethylglycine, ADP, AMP, betaine, phenylalanine, and uridine.
      Furthermore, alterations in one-carbon metabolism, supported by both metabolic
      and transcriptional changes, were observed. These included reduced demethylation
      of betaine to dimethylglycine and the reduced expression of genes coding for
      transsulfuration pathway enzymes, which appears to preserve methionine levels,
      but may limit glutathione synthesis. Overall, the combined approach is
      advantageous as it identifies changes not only at the single gene or metabolite
      level but also deregulated pathways, thus providing critical insight into changes
      accompanying fatty liver disease. Graphical abstract A Evaluation of RNA
      integrity before and after HR-MAS 1H-NMR of intact mouse liver tissue. B
      Metabolite concentrations and gene expression levels assessed in ob/ob
      (steatotic) and ob/+ (control) mice using HR-MAS 1H-NMR and qRT-PCR,
      respectively.

PMID- 27896395
TI  - Level of evidence of free papers presented at the European Society of Sports
      Traumatology, Knee Surgery and Arthroscopy congress from 2008 to 2016.
AB  - PURPOSE: The European Society of Sports Traumatology, Knee Surgery and
      Arthroscopy (ESSKA) congress is an important venue, and the research presented
      can be a critical source of information used to impact clinical decisions and
      health policies. The purpose of this study was to evaluate the level of evidence
      of clinical free papers presented at the ESSKA congress from 2008 to 2016.
      Moreover, this study evaluated whether there were any changes in the distribution
      of level of evidence over time. METHODS: Two reviewers screened the free papers
      presented at the ESSKA biannual congresses 2008-2016 for clinical evidence.
      Clinical papers included observational studies and trials involving direct
      interaction between an investigator and human subjects. Biomechanical studies,
      technique demonstrations, cadaveric studies, and panel discussions were excluded.
      The reviewers independently graded their level of evidence from level I (e.g.
      high-quality randomized trials) to level IV (e.g. case series and reports) using
      the classification system published by the American Academy of Orthopaedic
      Surgeons. RESULTS: Of 1036 free papers that were identified, 729 met the
      inclusion criteria and were evaluated. Overall, 18% of studies were level I, 24%
      level II, 25% level III, and 33% level IV evidence. There was a significant
      improvement in level of evidence over time (p < 0.0001), with the proportion of
      level I studies increasing most dramatically (9% in 2008, 20% in 2012, 24% in
      2016). Free papers studying the knee had higher levels of evidence than those
      evaluating other joints (p = 0.002). CONCLUSION: The level of evidence of
      clinical free papers presented at the ESSKA congress between 2008 and 2016 is
      high relative to other orthopaedic meetings. Moreover, there has been a
      significant improvement in the level of evidence over time. LEVEL OF EVIDENCE:
      Systematic review, Level IV.

PMID- 27896399
TI  - Cytochrome P450-mediated metabolism of triclosan attenuates its cytotoxicity in
      hepatic cells.
AB  - Triclosan is a widely used broad-spectrum anti-bacterial agent. The objectives of
      this study were to identify which cytochrome P450 (CYP) isoforms metabolize
      triclosan and to examine the effects of CYP-mediated metabolism on triclosan
      induced cytotoxicity. A panel of HepG2-derived cell lines was established, each
      of which overexpressed a single CYP isoform, including CYP1A1, CYP1A2, CYP1B1,
      CYP2A6, CYP2A7, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6,
      CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP4A11, and CYP4B1. The extent of triclosan
      metabolism by each CYP was assessed by reversed-phase high-performance liquid
      chromatography with online radiochemical detection. Seven isoforms were capable
      of metabolizing triclosan, with the order of activity being CYP1A2 > CYP2B6 >
      CYP2C19 > CYP2D6 ~ CYP1B1 > CYP2C18 ~ CYP1A1. The remaining 11 isoforms (CYP2A6,
      CYP2A7, CYP2A13, CYP2C8, CYP2C9, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP4A11, and
      CYP4B1) had little or no activity toward triclosan. Three metabolites were
      detected: 2,4-dichlorophenol, 4-chlorocatechol, and 5'-hydroxytriclosan.
      Consistent with the in vitro screening data, triclosan was extensively
      metabolized in HepG2 cells overexpressing CYP1A2, CYP2B6, CYP2C19, CYP2D6, and
      CYP2C18, and these cells were much more resistant to triclosan-induced
      cytotoxicity compared to vector cells, suggesting that CYP-mediated metabolism of
      triclosan attenuated its cytotoxicity. In addition, 2,4-dichlorophenol and 4
      chlorocatechol were less toxic than triclosan to HepG2/vector cells. Conjugation
      of triclosan, catalyzed by human glucuronosyltransferases (UGTs) and
      sulfotransferases (SULTs), also occurred in HepG2/CYP-overexpressing cells and
      primary human hepatocytes, with a greater extent of conjugation being associated
      with higher cell viability. Co-administration of triclosan with UGT or SULT
      inhibitors led to greater cytotoxicity in HepG2 cells and primary human
      hepatocytes, indicating that glucuronidation and sulfonation of triclosan are
      detoxification pathways. Among the 18 CYP-overexpressing cell lines, an inverse
      correlation was observed between cell viability and the level of triclosan in the
      culture medium. In conclusion, human CYP isoforms that metabolize triclosan were
      identified, and the metabolism of triclosan by CYPs, UGTs, and SULTs decreased
      its cytotoxicity in hepatic cells.

PMID- 27896398
TI  - Acute liver effects, disposition and metabolic fate of [14C]-fenclozic acid
      following oral administration to normal and bile-cannulated male C57BL/6J mice.
AB  - The distribution, metabolism, excretion and hepatic effects of the human
      hepatotoxin fenclozic acid were investigated following single oral doses of 10
      mg/kg to normal and bile duct-cannulated male C57BL/6J mice. Whole body
      autoradiography showed distribution into all tissues except the brain, with
      radioactivity still detectable in blood, kidney and liver at 72 h post-dose. Mice
      dosed with [14C]-fenclozic acid showed acute centrilobular hepatocellular
      necrosis, but no other regions of the liver were affected. The majority of the
      [14C]-fenclozic acid-related material recovered was found in the urine/aqueous
      cage wash, (49%) whilst a smaller portion (13%) was eliminated via the faeces.
      Metabolic profiles for urine, bile and faecal extracts, obtained using liquid
      chromatography and a combination of mass spectrometric and radioactivity
      detection, revealed extensive metabolism of fenclozic acid in mice that involved
      biotransformations via both oxidation and conjugation. These profiling studies
      also revealed the presence of glutathione-derived metabolites providing evidence
      for the production of reactive species by mice administered fenclozic acid.
      Covalent binding to proteins from liver, kidney and plasma was also demonstrated,
      although this binding was relatively low (less than 50 pmol eq./mg protein).

PMID- 27896400
TI  - Quantitative assessment of the supraspinatus tendon on MRI using T2/T2* mapping
      and shear-wave ultrasound elastography: a pilot study.
AB  - OBJECTIVE: To determine whether there is an association between T2/T2* mapping
      and supraspinatus tendon mechanical properties as assessed by shear-wave
      ultrasound elastography (SWE). MATERIALS AND METHODS: This HIPAA-compliant
      prospective pilot study received approval from our hospital's institutional
      review board. Eight patients (3 males/5 females; age range 44-72 years) and nine
      shoulders underwent conventional shoulder MRI, T2/T2* mapping on a 3-T scanner,
      and SWE. Two musculoskeletal radiologists reviewed the MRI examinations in
      consensus for evidence of supraspinatus tendon pathology, with tear size measured
      for full-thickness tears. T2/T2* values and ultrasound shear-wave velocities
      (SWV) were calculated in three corresponding equidistant regions of interest
      (ROIs) within the insertional 1-2 cm of the supraspinatus tendon (medial, middle,
      lateral). Pearson correlation coefficients between T2/T2* values and SWV, as well
      as among T2, T2*, SWV and tear size, were calculated. RESULTS: There was a
      significant negative correlation between T2* and SWV in the lateral ROI (r = 
      0.86, p = 0.013) and overall mean ROI (r = -0.90, p = 0.006). There was
      significant positive correlation between T2 and measures of tear size in the
      lateral and mean ROIs (r range 0.71-0.77, p range 0.016-0.034). There was
      significant negative correlation between SWV and tear size in the middle and mean
      ROIs (r range -0.79--0.68, p range 0.011-0.046). CONCLUSION: Our pilot study
      demonstrated a potential relationship between T2* values and shear wave velocity
      values in the supraspinatus tendon, a finding that could lead to an improved,
      more quantitative evaluation of the rotator cuff tendons.

PMID- 27896401
TI  - Sleeve Gastrectomy Combined with the Simplified Hill Repair in the Treatment of
      Morbid Obesity and Gastro-esophageal Reflux Disease: Preliminary Results in 14
      Patients.
AB  - BACKGROUND: Our aim is to report our initial experience with a novel technique
      which addresses morbid obesity and gastro-esophageal reflux disease (GERD)
      simultaneously by combination of laparoscopic sleeve gastrectomy (LSG) and
      simplified laparoscopic Hill repair (sLHR). METHODS: Retrospective analysis of
      LSG+sLHR patients >5 months postoperatively includes demographics, GERD status,
      proton-pump inhibitor (PPI) use, body mass index (BMI), excess BMI loss (EBMIL),
      complications and GERD-Health Related Quality of Life (GERD-HRQL) questionnaire.
      LSG+sLHR surgical technique: posterior cruroplasty,  standard LSG, fixation of
      the esophagogastric junction to the median arcuate ligament. RESULTS: Fourteen
      patients underwent LSG+sLHR [12 women and 2 men, mean (range) age 47 years (27
      57), BMI 41 kg/m2 (35-65)]. Five patients had previous gastric banding (GB). All
      had symptomatic GERD confirmed by gastroscopy and/or upper-gastrointestinal
      contrast study, two with chronic cough, 10 took PPI daily. Twelve had hiatus
      hernia and two patulous cardia at surgical exploration. Associated interventions
      were three GB removals and one cholecystectomy. Postoperative complication was
      one surgical site infection. Follow-up of all patients at median 12.5 months (5
      17) is as follows: symptomatic GERD 3/14 patients, chronic cough 0/14, daily PPI
      use in 1/14, mean EBMIL 68% (17-120), satisfaction 93%, mean GERD-HRQL score
      3,28/50 (0-15), with 4 patients 0/50, occasional bloatedness in 2 patients and
      dysphagia not reported. CONCLUSION: The novel technique which combines LSG with
      sLHR is feasible, safe and can be associated with GB removal. Preliminary results
      showed patient satisfaction, high remission rate of preexisting GERD, decrease in
      PPI use and unimpaired weight loss. Further evaluation is necessary in a
      controlled and staged manner to establish the technique's real effectiveness.

PMID- 27896402
TI  - Multifocal Versus Solitary Papillary Thyroid Carcinoma: Reply.

PMID- 27896403
TI  - Histology is a Prognostic Indicator After Pulmonary Metastasectomy from Renal
      Cell Carcinoma.
AB  - OBJECTIVES: There are only a few detailed reports concerning the prognosticators
      following surgical resection of pulmonary metastases (PMs) from renal cell
      carcinoma (RCC). We investigated the prognosis of patients with RCC PMs
      undergoing pulmonary metastasectomy and identified prognostic factors in a multi
      institutional retrospective study. METHODS: We retrospectively evaluated 84
      patients who underwent resection of PMs from RCC between 1993 and 2014. We
      assessed the clinicopathological characteristics, focusing on the histological
      findings of PMs. We classified the histology into three types: pure clear cell
      carcinoma (N = 68), clear cell carcinoma combined with other histology type (N =
      8), and non-clear cell carcinoma (N = 8). We examined the relationship between
      these histological types and the prognosis of patients with PMs from RCC.
      RESULTS: Complete resection was achieved in 78 patients (93%). The 5-year overall
      survival rate after metastasectomy was 59.7%. In multivariate analysis, three
      factors were found to be independent favorable prognostic factors of overall
      survival after lung metastasectomy [tumor size <2 cm, hazard ratio (HR) = 0.31,
      95% confidence interval (CI) 0.13-0.78, P = 0.012; clear cell type, HR = 0.37,
      95% CI 0.16-0.83, P = 0.025; and complete resection, HR = 0.27, 95% CI 0.10-0.78,
      P = 0.015]. CONCLUSIONS: This study indicates that a histological finding of the
      clear cell type is a significant favorable prognostic factor in addition to
      complete resection and a tumor size <2 cm. Histological evaluation of PM lesions
      is important for predicting survival after metastasectomy.

PMID- 27896404
TI  - En Bloc Resection with Major Blood Vessel Reconstruction for Locally Invasive
      Retroperitoneal Paragangliomas: A 15-Year Experience with Literature Review.
AB  - BACKGROUND: Retroperitoneal paragangliomas (PGs) are a rare subgroup of
      neuroendocrine tumors that are commonly located alongside the abdominal aorta.
      Complete tumor resection is thought to be restricted in patients with major blood
      vessel involvement. However, no study has specifically focused on aggressive
      surgical treatment in such patients. We evaluated the value of en bloc resection
      with major blood vessel reconstruction for locally invasive retroperitoneal PGs.
      METHODS: Twenty-nine patients with retroperitoneal PGs with major blood vessel
      involvement were included in this retrospective study. Survival was compared
      between patients who underwent en bloc resection with major blood vessel
      reconstruction and those who underwent medical treatment. Prognostic predictors
      were analyzed in patients who underwent en bloc resection with major blood vessel
      reconstruction. RESULTS: All 11 patients who underwent medical treatment obtained
      a pathological diagnosis by computed tomography-guided percutaneous needle
      biopsy. All 18 patients who underwent en bloc resection with major blood vessel
      reconstruction achieved complete tumor resection. Overall survival was higher in
      patients who underwent complete tumor resection than in those who underwent
      medical treatment (p < 0.05). No perioperative mortality occurred in patients who
      underwent complete tumor resection. Patients with no metastasis, no organ
      invasion, R0 resection, a Ki-67 index of <=3%, and a tumor diameter of <=11.7 cm
      showed better tumor-free survival (p < 0.05). CONCLUSIONS: En bloc resection with
      major blood vessel reconstruction can be successfully performed and provide
      satisfactory outcomes for patients with locally invasive retroperitoneal PGs.
      This technique may become a standard surgical strategy for properly selected
      patients.

PMID- 27896405
TI  - The Totally Implantable Venous Access Device with Occurrence of Pneumothorax
      Still Remains an Issue.

PMID- 27896406
TI  - Evaluation of Rex Shunt on Cavernous Transformation of the Portal Vein in
      Children.
AB  - BACKGROUND: Children with cavernous transformation of the portal vein (CTPV)
      develop severe complications from prehepatic portal hypertension, such as
      recurrent variceal bleeding and thrombocytopenia. In this study, we reported the
      results of 30 children with symptomatic CTPV that were treated by a Rex shunt.
      The effectiveness of this surgical approach was evaluated. METHODS: A
      retrospective review was performed of 30 children aged between 3 and 18 years
      with CTPV, who underwent a Rex shunt between 2008 and 2015. All children were
      evaluated based on symptoms, complete blood count, portal system color-flow
      Doppler ultrasound or computed tomography angiography portography and gastroscopy
      for gastroesophageal varices pre- and postoperatively. Children were also
      evaluated during follow-up. Intraoperative evaluations included liver biopsy,
      portography and portal pressure. RESULTS: Twenty-one patients demonstrated
      intermittent bleeding from gastroesophageal varices, 3 patients showed
      hypersplenism with varying degrees of leucopenia, anemia and thrombocytopenia,
      and in 6 patients both bleeding and hypersplenism were observed. Rex was
      successful in 28 patients (93.3%). The portal pressure immediately decreased
      significantly after placing of the shunt (P < 0.01). During the clinical follow
      up period within 2-82 months, transaminase levels were maintained in the normal
      range. Blood flow velocity and diameter of the left portal vein significantly
      increased after surgery (P < 0.01). In addition, leukocyte and platelet counts
      increased postoperatively and anemia improved significantly (P < 0.01).
      Gastroscopy results indicated that the degree of gastroesophageal varices
      significantly alleviated postoperatively within 3 months and 1 year (P < 0.01).
      In 2 patients who demonstrated nodular cirrhosis and chronic active hepatitis,
      success of the Rex shunt was not achieved after operation. We found that for Rex
      effectiveness hepatic pathology and patient age were major determinants.
      CONCLUSION: Rex shunt is an effective approach for the treatment of children
      suffering from CTPV at an early stage that do not show additional liver lesions.

PMID- 27896407
TI  - Mixed-Methods Assessment of Trauma and Acute Care Surgical Quality Improvement
      Programs in Peru.
AB  - BACKGROUND: Evidence for the positive impact of quality improvement (QI) programs
      on morbidity, mortality, patient satisfaction, and cost is strong. Data regarding
      the status of QI programs in low- and middle-income countries, as well as in
      depth examination of barriers and facilitators to their implementation, are
      limited. METHODS: This cross-sectional, descriptive study employed a mixed
      methods design, including distribution of an anonymous quantitative survey and
      individual interviews with healthcare providers who participate in the care of
      the injured at ten large hospitals in Lima, Peru. RESULTS: Key areas identified
      for improvement in morbidity and mortality (M&M) conferences were the
      standardization of case selection, incorporation of evidence from the medical
      literature into case presentation and discussion, case documentation, and the
      development of a clear plan for case follow-up. The key barriers to QI program
      implementation were a lack of prioritization of QI, lack of sufficient human and
      administrative resources, lack of political support, and lack of education on QI
      practices. CONCLUSIONS: A national program that makes QI a required part of all
      health providers' professional training and responsibilities would effectively
      address a majority of identified barriers to QI programs in Peru. Specifically,
      the presence of basic QI elements, such as M&M conferences, should be required at
      hospitals that train pre-graduate physicians. Alternatively, short of this
      national-level organization, efforts that capitalize on local examples through
      apprenticeships between institutions or integration of QI into continuing medical
      education would be expected to build on the facilitators for QI programs that
      exist in Peru.

PMID- 27896408
TI  - Is Routine Prophylactic Cholecystectomy Necessary During Gastrectomy for Gastric
      Cancer?
AB  - BACKGROUND: Performing routine prophylactic cholecystectomy during gastrectomy in
      gastric cancer patients has been controversial. The frequency of cholelithiasis,
      cholecystitis, and cholangitis after gastrectomy has not been reported for large
      patient populations, so we carried out this retrospective study to aid the
      assessment of the necessity for prophylactic cholecystectomy. METHODS: This
      retrospective study reviewed 969 patients with gastric cancer who underwent
      distal gastrectomies with Billroth I reconstructions (DG) or total gastrectomies
      with Roux-en-Y reconstructions (TG), preserving the gallbladder, between January
      2000 and May 2012. Risk factors for cholelithiasis, cholecystitis, and
      cholangitis after gastrectomy were evaluated using logistic regression analysis.
      RESULTS: The median follow-up period after gastrectomy was 48 months (range 12
      159 months). After gastrectomy, cholelithiasis occurred in 6.1% (59/969) patients
      and cholecystitis and/or cholangitis occurred in 1.2% (12/969) patients. The
      method used for gastrectomy was an independent risk factor for both
      cholelithiasis (TG/DG: OR (95%CI): 1.900 (1.114-3.240), p = 0.018) and
      cholecystitis and/or cholangitis (TG/DG: OR (95%CI): 8.325 (1.814-38.197), p =
      0.006). In patients who developed cholelithiasis, the incidence of cholecystitis
      and/or cholangitis was 31.3% (10/32) after TG, but only 7.4% after DG.
      CONCLUSIONS: Prophylactic cholecystectomy may be unnecessary in distal
      gastrectomy with Billroth I reconstruction.

PMID- 27896409
TI  - Post-resection Prognosis of Combined Hepatocellular Carcinoma-Cholangiocarcinoma
      According to the 2010 WHO Classification.
AB  - BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHC) has
      wide histological diversity. We intended to investigate the prognostic influence
      of tumor types of cHC. METHODS: We analyzed the clinical and pathological
      features of cHC along 2010 WHO classification. Study group was 100 cHC patients
      who underwent primary resection. Control group comprised 200 propensity score
      matched patients with intrahepatic cholangiocarcinoma (ICC). RESULTS: In cHC
      group, tumor diameter was 4.4 +/- 2.8 cm and 95 patients had single tumor. They
      were classified as classical type in 46 and subtypes with stem cell (SC) features
      in 54. Subtypes with SC features included typical in 16, intermediate cell in 22,
      and cholangiolocellular in 16. Their 1- and 3-year tumor recurrence rates were
      31.7 and 59.8%; and 1- and 3-year patient survival rates were 92.5 and 77.3%,
      respectively. Tumor recurrence (p = 0.008) and patient survival (p = 0.005) rates
      were different according to tumor types. Further stratification by subtypes with
      SC features resulted in prognostic stratification in tumor recurrence (p = 0.045)
      and patient survival (p = 0.042). However, tumor stage was the only independent
      risk factor for tumor recurrence and patient survival. Comparing with ICC control
      group, cHC group showed no significant difference in rates of tumor recurrence (p
      = 0.523), but better survival outcomes (p = 0.008). Median post-recurrence
      patient survival period was 20 months in cHC patients and 6 months in ICC
      patients (p = 0.001). CONCLUSIONS: Our results indicated that there would be
      close relationship between the post-resection prognosis and histological types
      according to the 2010 WHO classification, but these histological types did not
      become an independent prognostic factor.

PMID- 27896410
TI  - Low Incidence of Lymph Node Metastasis After Resection of Hepatitis Virus-Related
      Intrahepatic Cholangiocarcinoma.
AB  - BACKGROUND AND OBJECTIVES: We determined the rates of initial lymph node
      metastasis following curative resection of mass-forming type-intrahepatic
      cholangiocarcinoma (ICC) in patients with and without hepatitis virus infection.
      METHODS: We enrolled 87 patients between January 2000 and December 2013 with ICC
      without preoperative lymph node metastasis and without lymph node dissection.
      Patients included 32 who were seropositive for hepatitis B or C virus (virus
      group) and 55 who had no evidence of hepatitis virus infection (nonvirus group).
      Postsurgical outcomes and initial recurrence of the groups were compared, and we
      identified the risk factors for lymph node metastasis as initial recurrence.
      RESULTS: Platelet counts and prothrombin activities were significantly lower in
      the virus group compared with those of the nonvirus group. The number of patients
      with chronic hepatitis or liver cirrhosis was significantly higher in the virus
      group compared with the nonvirus group as well as their respective rates of
      recurrence-free survival. One patient (3%) in the virus group and 14 patients
      (25%) in the nonvirus group had lymph node metastasis as initial recurrence (p =
      0.007). Multivariate analysis revealed that the absence of hepatitis virus
      infection as an independent risk factor (p = 0.047). CONCLUSION: Hepatitis virus
      associated mass-forming-type ICC confers a low risk of lymph node metastasis as
      initial postoperative recurrence.

PMID- 27896411
TI  - The Effects of Intravenous Lidocaine Infusions on the Quality of Recovery and
      Chronic Pain After Robotic Thyroidectomy: A Randomized, Double-Blinded,
      Controlled Study.
AB  - BACKGROUND: The effect of the systemic lidocaine on postoperative recovery has
      not been definitively investigated despite its analgesic efficacy after surgery.
      The aim of this randomized, double-blinded, controlled study was to evaluate the
      effect of intravenously administered lidocaine on the quality of recovery and on
      acute and chronic postoperative pain after robot-assisted thyroidectomy. METHODS:
      Ninety patients who were undergoing robotic thyroidectomy were randomly assigned
      to the lidocaine or the control groups. The patients received 2 mg/kg of
      lidocaine followed by continuous infusions of 3 mg/kg/h of lidocaine (Group L) or
      the same volume of 0.9% normal saline (Group C) intravenously during anesthesia.
      The acute pain profiles and the quality of recovery, which was assessed using the
      quality of recovery-40 questionnaire (QoR-40), were evaluated for 2 days
      postoperatively. Chronic postsurgical pain (CPSP) and sensory disturbances at the
      surgical sites were evaluated 3 months after surgery. RESULTS: The QoR-40 and
      pain scores that were assessed during the 2 days that followed surgery were
      largely comparable between the groups. However, CPSP was more prevalent in the
      Group C than in the Group L (16/43 vs. 6/41; p = 0.025). The tactile sensory
      score 3 months after the operation was significantly greater in the Group L than
      in the Group C (7 vs. 5; p = 0.001). CONCLUSION: Systemic lidocaine
      administration was associated with reductions in CPSP and sensory impairment
      after robot-assisted thyroidectomy although it was not able to reduce acute
      postsurgical pain or improve the quality of recovery. Trial registry number
      NCT01907997 ( http://clinicaltrials.gov ).

PMID- 27896413
TI  - Endovascular Revascularization of Hemodialysis Thrombosed Grafts with the
      Hydrodynamic Thrombectomy Catheter. Our 7-Year Experience.
AB  - PURPOSE: To evaluate the efficacy and safety of the hydrodynamic thrombectomy
      catheter (AngioJet DVX) in the salvage of thrombosed hemodialysis vascular
      grafts. MATERIALS AND METHODS: A retrospective study was designed, including all
      patients with occluded arteriovenous grafts treated with the AngioJet system
      between 2007 and 2014 in our institution. Outcomes included technical success,
      clinical success, complications, and primary and secondary patencies. Procedural
      success was defined as angiographic confirmation of flow restoration, the
      presence of a pulsatile thrill along the graft, and successful resumption of at
      least one hemodialysis session. Primary and secondary patencies after first AVG
      thrombectomy were calculated with Kaplan-Meier curves. Cox regression was used to
      determine prognostic factors of primary patency after every thrombectomy episode.
      RESULTS: A total of 149 thrombectomies were performed in 68 grafts. After
      thrombectomy, endovascular treatment of one or more stenosis was performed in all
      cases. Technical success was 93% and clinical success was 86%. Complications
      occurred in 7 thrombectomies, most of them were minor except for one anastomosis
      rupture requiring surgery. Primary and secondary patencies were 52, 41, and 23
      and 76, 68, and 57% at 3, 6 and 12 months, respectively. Independent prognostic
      factors of poor patency after every thrombectomy episode were the presence of
      residual thrombus (OR 1.831, P = 0.008) and time from last thrombosis (less than
      1 month; and OR 7.116, P < 0.001). CONCLUSION: Percutaneous mechanical
      thrombectomy with AngioJet is a safe technique with a high-clinical success rate.
      The presence of residual thrombus after thrombectomy and early re-occlusions are
      related to poorer results.

PMID- 27896412
TI  - The bacterial quorum-sensing molecule, N-3-oxo-dodecanoyl-L-homoserine lactone,
      inhibits mediator release and chemotaxis of murine mast cells.
AB  - OBJECTIVE: Bacterial colonization relies on communication between bacteria via so
      called "quorum-sensing molecules", which include the acyl-homoserine lactone
      group. Certain acyl-homoserine lactones can modulate mammalian cell function and
      are thought to contribute to bacterial pathogenicity. Given the role of mast
      cells in host defense, we investigated the ability of acyl-homoserine lactones to
      modulate mast cell function. METHODS: We utilized murine primary mast cell
      cultures to assess the effect of acyl-homoserine lactones on degranulation and
      cytokine release in response to different stimuli. We also assessed cell
      migration in response to chemoattractants. The effect of acyl-homoserine lactones
      in vivo was tested using a passive cutaneous anaphylaxis model. RESULTS: Two of
      the tested quorum-sensing molecules, N-3-oxo-dodecanoyl-L-homoserine lactone and
      N-Dodecanoyl-L-homoserine lactone, inhibited IgE dependent and independent
      degranulation and mediator release from primary mast cells. Further testing of N
      3-oxo-dodecanoyl-L-homoserine lactone, the most potent inhibitor and a product of
      Pseudomonas aeruginosa, revealed that it also attenuated chemotaxis and LPS
      induced cytokine production. In vivo, N-3-oxo-dodecanoyl-L-homoserine lactone
      inhibited the passive cutaneous anaphylaxis response in mice. CONCLUSION: The
      ability of N-3-oxo-dodecanoyl-L-homoserine lactone to stabilize mast cells may
      contribute to the pathogenicity of P. aeruginosa but could potentially be
      exploited therapeutically in allergic disease.

PMID- 27896415
TI  - Predicting risk factors for varicella zoster virus infection and postherpetic
      neuralgia after hematopoietic cell transplantation using ordered logistic
      regression analysis.
AB  - To identify risk factors for varicella zoster virus (VZV) infection and
      postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT), we
      conducted a retrospective chart review of 163 consecutive patients who underwent
      HCT between November 2004 and July 2014. Overall, the male/female (M/F) ratio was
      80/83, median age at HCT was 54 (range 15-69) years, and autologous/allogeneic
      HCT (auto/allo-HCT) ratio was 71/92. Forty-four patients [M/F, 25/19; median age,
      57 (range: 16-68) years; auto/allo-HCT, 26/18] developed VZV infection after HCT.
      All cases were successfully treated with acyclovir (ACV) or valacyclovir, and
      there was no VZV-related death. Nine (20%) of the 44 patients [M/F, 5/4; median
      age, 58 (range: 21-63) years; auto/allo-HCT, 7/2] developed PHN after resolution
      of zoster. Multivariate ordered logistic analysis identified receiving
      immunosuppressive therapy at the cessation of ACV [odds ratio (OR) = 74.53; 95%
      confidence interval (CI) = 6.99-794.32; P = 0.0004] as a risk factor for VZV
      infection and PHN in allo-HCT recipients. However, in auto-HCT recipients, only
      advanced age was identified as a risk factor (OR = 1.06, 95% CI = 1.002-1.127, P
      = 0.0429). Our findings indicate receiving immunosuppressive therapy at the
      cessation of ACV is a significant risk factor for allo-HCT recipients, while
      advanced age is a significant risk factor for auto-HCT recipients.

PMID- 27896414
TI  - Closure Devices for Iatrogenic Thoraco-Cervical Vascular Injuries.
AB  - INTRODUCTION: The unintentional arterial placement of a central venous line can
      have catastrophic complications. The purpose of this systematic review is to
      assess and analyse the available evidence regarding the use of the various
      vascular closure devices (VCDs) for the management of iatrogenic thoraco-cervical
      arterial injuries (ITCAI). METHODS: A systematic review was performed according
      to PRISMA guidelines. RESULTS: Thirty-two relevant case series and case reports
      were identified with a total of 69 patients having being studied. In the majority
      of the studies, plug-based VCDs were used (81%) followed by suture-based devices
      (19%). The majority of studies reported successful outcomes from the use of VCDs
      in terms of achieving immediate haemostasis without any acute complications. Long
      term follow-up data were only available in nine studies with only one case of
      carotid pseudoaneurysm being reported after 1-month post-procedure. All other
      cases had no reported long-term complications. Five studies performed direct or
      indirect comparisons between VCDs and other treatments (open surgery or stent
      grafting) suggesting no significant differences in safety or effectiveness.
      CONCLUSION: Although there is limited evidence, VCDs appear to be safe and
      effective for the management of ITCAIs. Further research is warranted regarding
      the effectiveness of this approach in comparison to surgery and in order to
      identify those patients who are more likely to benefit from this minimally
      invasive approach.

PMID- 27896416
TI  - Prevalence of isolated maxillary lateral incisor agenesis in Syrian adolescents.
AB  - PURPOSE: This research is designed to obtain a better understanding and provide
      more insight of this phenomenon through evaluating the prevalence of congenital
      absence of maxillary lateral incisors in a Syrian population. METHODS: The method
      involved clinical examination of 8000 school children with an equal number of
      males and females (age range 12-15 years) to identify students only affected by
      bilateral or unilateral congenital absence of maxillary lateral incisors.
      Agenesis was determined based on radiological evidence. RESULTS: The results of
      this study showed that the prevalence of isolated maxillary lateral incisors
      agenesis was 1.15%. In the sample studied, 66.3% of the patients were female and
      33.7% were male (p < 0.05). Absence was bilateral in 47.8% of patients and
      unilateral in 52.2%. Of the unilateral cases, 48% occurred on the right side and
      52% on the left side, and the contralateral maxillary incisor was found to be
      microdont in 43.75%, right lateral in 47.6%, and left lateral in 52.4%.
      CONCLUSION: The results of this study allow the conclusion that the prevalence of
      isolated maxillary lateral incisors agenesis in a Syrian population is within the
      average range with regard to other populations. A significant familial component
      to the etiology of maxillary lateral incisors agenesis was found.

PMID- 27896417
TI  - Age assessment based on third molar mineralisation : An epidemiological
      radiological study on a Central-European population.
AB  - PURPOSE: The method published in 1973 by Demirjian et al. to assess age based on
      the mineralisation stage of permanent teeth is standard practice in forensic and
      orthodontic diagnostics. From age 14 onwards, however, this method is only
      applicable to third molars. No current epidemiological data on third molar
      mineralisation are available for Caucasian Central-Europeans. Thus, a method for
      assessing age in this population based on third molar mineralisation is
      presented, taking into account possible topographic and gender-specific
      differences. METHODS: The study included 486 Caucasian Central-European
      orthodontic patients (9-24 years) with unaffected dental development. In an
      anonymized, randomized, and blinded manner, one orthopantomogram of each patient
      at either start, mid or end of treatment was visually analysed regarding the
      mineralisation stage of the third molars according to the method by Demirjian et
      al. Corresponding topographic and gender-specific point scores were determined
      and added to form a dental maturity score. Prediction equations for age
      assessment were derived by linear regression analysis with chronological age and
      checked for reliability within the study population. RESULTS: Mineralisation of
      the lower third molars was slower than mineralisation of the upper third molars,
      whereas no jaw-side-specific differences were detected. Gender-specific
      differences were relatively small, but girls reached mineralisation stage C
      earlier than boys, whereas boys showed an accelerated mineralisation between the
      ages of 15 and 16. CONCLUSIONS: The global equation generated by regression
      analysis (age = -1.103 + 0.268 * dental maturity score 18 + 28 + 38 + 48) is
      sufficiently accurate and reliable for clinical use. Age assessment only based on
      either maxilla or mandible also shows good prognostic reliability.

PMID- 27896418
TI  - Effects of two different removable functional appliances on depth of the
      posterior airway space : A retrospective cephalometric study.
AB  - OBJECTIVES: Aim of the study was the comparison of treatment effects upon
      pharyngeal depth in patients treated with either (1) S-II-appliance or (2)
      Activator. METHODS: Pre- and posttreatment lateral cephalograms of 73 patients
      were analyzed using a customized set of measurements. According to predefined
      criteria, patients were either treated with S-II-appliance or Activator.
      Pharyngeal depth was assessed from cranial to caudal at six levels (P1 to P6).
      Paired t tests were used for intragroup and t tests for independent samples for
      intergroup comparisons. Results were considered statistically significant at p <=
      0.05. RESULTS: 37 (22 female, 15 male) patients were treated with the S-II
      appliance (mean pretreatment age 11.1 +/- 1.07 years), and 36 (20 female, 16
      male) patients with an Activator (mean pretreatment age 11.3 +/- 1.12 years).
      Mean treatment time was 14 months for the S-II-appliance and 12 months for the
      Activator. Most measurements at the different levels showed an average increase
      ranging from approximately 0.5 mm to almost 2 mm. Changes were more pronounced in
      S-II patients. In contrast to intergroup comparisons, some intragroup comparisons
      revealed statistically significant differences at levels P5 (p = 0.0062) and P6
      (p = 0.0155) in S-II patients and at P1-level (p = 0.0197) in Activator patients.
      CONCLUSIONS: Both appliances similarly led to an increase of the pharyngeal
      depth. The sites of statistically significant changes differed.

PMID- 27896419
TI  - Effects of enamel sealing on shear bond strength and the adhesive remnant index :
      Study of three fluoride-releasing adhesives in combination with metal and ceramic
      brackets.
AB  - OBJECTIVES: Selected combinations of materials were used to create tooth-adhesive
      bracket complexes to evaluate shear bond strength (SBS) and the adhesive remnant
      index (ARI) with regard to enamel sealing. METHODS: Four adhesive systems also
      appropriate for use as enamel sealants were combined with four bracket types,
      resulting in 16 adhesive-bracket combinations, each of which was tested on 15
      permanent bovine incisors. Sealant-adhesives included two recently introduced
      fluoride-releasing systems (Riva bond LC(r) and go!(r)), one established primer
      (Opal(r) SealTM), and one commonly used adhesive as control (TransbondTM XT).
      Brackets included two metal (discovery(r) by Dentaurum and Sprint(r)) and two
      ceramic (discovery(r) pearl and GLAM(r)) systems. After embedding the bovine
      teeth, bonding the brackets to their surface, and storing the resultant samples
      as per DIN 13990-2 with modifications, an SBS test was performed by applying the
      shear force directly at the bracket base in an incisocervical direction. Then the
      ARI scores were determined. RESULTS: Discovery(r) + TransbondTM XT yielded the
      highest (47.2 MPa) and GLAM(r) + go!(r) the lowest (17.0 MPa) mean SBS values.
      Significant differences (p < 0.0001) were found between metal and ceramic
      brackets of the same manufacturers (Dentaurum and Forestadent). Our ratings of
      the failure modes upon debonding predominantly yielded ARI 0 or 1. The high SBS
      values and low ARI scores observed with discovery(r) + Transbond XTTM were
      reflected in a high rate of enamel fracture, which occurred on 11 of the 15 tooth
      specimens in this group. CONCLUSIONS: All sealant-bracket combinations were found
      to yield levels of SBS adequate for clinical application. SBS values and ARI
      scores varied significantly depending on which sealant-brackets were used.

PMID- 27896420
TI  - Level of agreement between three-dimensional volumetric ultrasound and real-time
      conventional ultrasound in the assessment of synovitis, tenosynovitis and
      erosions in rheumatoid arthritis patients.
AB  - The aim of the study was to assess agreement between three-dimensional volumetric
      ultrasound (3D US) performed by inexperienced staff and real-time conventional
      ultrasound (2D US) performed by experienced rheumatologists in detecting and
      scoring rheumatoid arthritis (RA) lesions. Thirty-one RA patients underwent
      examination of seven joints by 2D and 3D US for synovitis and tenosynovitis in B
      and PD modes and erosions in B mode. A global score for synovitis and global
      counts for synovitis, tenosynovitis and erosions were also calculated for every
      patient. Agreement between 2D and 3D US was analysed for counts and scores at the
      patient level with the intraclass correlation coefficient (ICC) and for counts at
      the joint level with Cohen's kappa coefficient. B-mode synovitis was detected at
      a median of five joints in each patient, frequently in wrists and hand joints but
      less frequently in foot joints. PD-mode synovitis, tenosynovitis and erosions
      were detected less frequently. All ICCs for agreement between 2D and 3D US
      findings were significant. All kappa coefficients were significant for B- and PD
      mode synovitis and for erosions (except PIP3), while those for tenosynovitis were
      only significant for MCP2 (B and PD modes) and PIP2 (B mode). Although the 3D US
      volumes were acquired by inexperienced operators, agreement between 2D and 3D US
      was acceptable in detecting and scoring synovitis. A higher level of agreement
      was attained for patient-level global scores and counts than for individual
      joints.

PMID- 27896422
TI  - Transcatheter aortic matryoshka doll: thrombosis.

PMID- 27896421
TI  - Multiple behavioral factors are associated with occurrence of large, flat
      colorectal polyps.
AB  - PURPOSE: The prevalence of advanced dysplasia and synchronous lesions is
      particularly high in patients with large, flat colorectal polyps. However, the
      impact of lifestyle on the development of such polyps is poorly investigated.
      Hence, this study aims to identify associations between behavioral factors and
      the occurrence of large, flat colorectal polyps. METHODS: Behavioral factors were
      retrospectively analyzed in patients with large, flat polyps and control patients
      with at most one diminutive polyp. Information on lifestyle factors,
      comorbidities, and demographic parameters were determined by a structured, self
      administered questionnaire. RESULTS: Questionnaires of 350 patients with large,
      flat polyps and 489 control patients were included in the analysis. Most large,
      flat colorectal polyps contained adenoma with low-grade neoplasia and were
      located in the right colon. Multivariate analysis showed that advanced age (per 1
      year increase-OR 1.09, CI 1.07-1.11, p < 0.0001), frequent cigarette smoking (OR
      2.04, CI 1.25-3.32, p = 0.0041), daily consumption of red meat (OR 3.61, CI 1.00
      12.96, p = 0.0492), and frequent bowel movements (OR 1.62, CI 1.13-2.33, p =
      0.0093) were independent risk factors for occurrence of large, flat colorectal
      polyps. In contrast, frequent intake of cereals (OR 0.62, CI 0.44-0.88, p =
      0.0074) was associated with a reduced risk. CONCLUSION: Multiple behavioral
      factors modulate the risk for developing large, flat colorectal polyps. This
      knowledge can be used to improve prevention of colorectal cancer.

PMID- 27896423
TI  - Long-term outcomes following H-type tracheoesophageal fistula repair in infants.
AB  - PURPOSE: To evaluate outcomes following repair of H-type tracheoesophageal
      fistula (TEF). METHODS: Retrospective chart review of infants with H-type TEF
      treated at our institution between 2000 and 2014. Patient demographics, surgical
      management, and postoperative function were evaluated. RESULTS: Of the 268
      patients with esophageal atresia/TEF treated at our center, 16 (6%) had an H-type
      TEF (10 males). Thirteen (81%) had associated anomalies. All patients were
      symptomatic: choking and sputtering were the most common presentation (n = 10,
      63%). Diagnosis Age at diagnosis was 8 days (1 day-34 months). All patients were
      diagnosed based on a single esophagogram. Prior to surgery, 12 (75%) patients
      underwent bronchoscopy and 11 underwent cannulation of the TEF tract. Surgery All
      patients underwent open repair. One was started thoracoscopically but converted
      to open due to esophageal sero-muscular injury. Repair was achieved in all
      patients via a transcervical approach (right-sided incision in 15). One patient
      had an unsuccessful prior attempt at repair using tissue glue. Following TEF
      division, 11 patients had tissue interposition grafts placed (9 muscle, 2 fat).
      Postoperative course Eight (50%) patients had postoperative vocal cord paresis (6
      right-sided, 2 bilateral). A patient developed recurrent TEF 78 days
      postoperatively that was subsequently repaired. Follow-up At 41 months (8-143),
      there were no mortalities, all patients with vocal cord paresis were asymptomatic
      despite the fact that only 3 of 8 (38%) regained function, and nine (56%)
      patients had gastro-esophageal reflux requiring treatment. CONCLUSIONS: This
      large, single-center series demonstrates that H-type TEF can be diagnosed with
      esophagogram at an early age. Postoperative recurrent laryngeal nerve paresis and
      gastro-esophageal reflux disease are common following repair. Although most
      patients with vocal cord paresis eventually become asymptomatic, two-thirds do
      not regain vocal cord function. This reinforces the importance of routine
      examination of vocal cord movement following H-type TEF repair.

PMID- 27896425
TI  - Probability and pattern of occult cervical lymph node metastases in primary
      parotid carcinoma.
AB  - The present study was undertaken to evaluate real probability and pattern of
      cervical occult lymph node metastases (OLNM) in primary parotid carcinoma (PPC).
      We carried out a retrospective analysis of 66 patients treated in years 1992-2010
      due to PPC, who underwent elective neck dissection (END). In search of risk
      factors for OLNM, we analysed the following parameters: age, sex, pT-Status,
      tumour size, skin invasion, facial nerve palsy, tumour fixation, extraparotid
      extension, localization, grade, histology, intra/periparotid LN metastases
      (IPLNM). OLNM was observed in 30.3% of patients. In a univariate analysis
      statistical significance was found for IPLNM, extraparotid extension and high
      risk histology. A multivariate analysis showed statistical significance only for
      the first variable. The most common location of cervical OLNM was level II (80%),
      then III (45%) and V (30%). In a compilation of our own material with data from
      the literature (5 series), we obtained a group of 80 patients with OLNM, selected
      out of 650 patients with cN0 (12.3%). The proportion of metastases to particular
      levels was the following: 69%-II, 22.5%-III, 20%-I,16%-V, 7.5%-IV. END should be
      carried out in case of all T3/T4a carcinomas with minimal range of levels II and
      III. Removal of levels Ib and Va is recommended as well. In the T1/T2 carcinomas
      with high grade/high risk histology, END should be performed including levels II
      and III.

PMID- 27896424
TI  - Dynamic expression analysis of early response genes induced by potato virus Y in
      PVY-resistant Nicotiana tabacum.
AB  - KEY MESSAGE: Dynamic transcriptional changes of the host early responses genes
      were detected in PVY-resistant tobacco varieties infected with Potato virus Y;
      PVY resistance is a complex process that needs series of stress responses. Potato
      virus Y (PVY) causes a severe viral disease in cultivated crops, especially in
      Solanum plants. To understand the molecular basis of plant responses to the PVY
      stress, suppression subtractive hybridization (SSH) and microarray approaches
      were combined to identify the potentially important or novel genes that were
      involved in early stages (12 h, 1, 2, 3, 5, 8 days) of tobacco response to PVY
      infection. Dynamic changes of the host plant early responses to PVY infection on
      a transcriptional level were detected. In total, 167 different expressed ESTs
      were identified. The majority of genes involved in the metabolic process were
      found to be down-regulated at 12 h and 1 day, and then up-regulated at least one
      later period. Genes related to signaling and transcriptions were almost up
      regulated at 12 h, 1 or 2 days, while stress response genes were almost up
      regulated at a later stage. Genes involved in transcription, transport, cell
      wall, and several stress responses were found to have changed expression during
      the PVY infection stage, and numbers of these genes have not been previously
      reported to be associated with tobacco PVY infection. The diversity expression of
      these genes indicated that PVY resistance is a complex process that needs a
      series of stress responses. To resist the PVY infection, the tobacco plant has
      numerous active and silent responses.

PMID- 27896426
TI  - Expression and characterization of a codon-optimized alkaline-stable carbonic
      anhydrase from Aliivibrio salmonicida for CO2 sequestration applications.
AB  - The CO2 mineralization process, accelerated by carbonic anhydrase (CA) was
      proposed for the efficient capture and storage of CO2, the accumulation of which
      in the atmosphere is the main cause of global warming. Here, we characterize a
      highly stable form of the cloned CA from the Gram-negative marine bacterium
      Aliivibrio salmonicida, named ASCA that can promote CO2 absorption in an alkaline
      solvent required for efficient carbon capture. We designed a mature form of ASCA
      (mASCA) using a codon optimization of ASCA gene and removal of ASCA signal
      peptide. mASCA was highly expressed (255 mg/L) with a molecular weight of
      approximately 26 kDa. The mASCA enzyme exhibited stable esterase activity within
      a temperature range of 10-60  degrees C and a pH range of 6-11. mASCA activity
      remained stable for 48 h at pH 10. We also investigated its inhibition profiles
      using inorganic anions, such as acetazolamide, sulfanilamide, iodide, nitrate,
      and azide. We also demonstrate that mASCA is capable of catalyzing the conversion
      of CO2 to CaCO3 (calcite form) in the presence of Ca2+. It should be noted that
      mASCA enzyme exhibits high production yield and sufficient stabilities against
      relatively high temperature and alkaline pH, which are required conditions for
      the development of more efficient enzymatic CCS systems.

PMID- 27896427
TI  - Predictors of motor developmental milestones during the first year of life.
AB  - : Studies suggest that both pre- and postnatal factors are predictors of age of
      attaining milestones in infancy. However, no studies evaluate the comparative
      strength of these predictors and the amount of the variance in development they
      explain. This study aimed to conduct a systematic evaluation of a broad selection
      of possible predictors of age at milestone attainment and to identify factors
      that explain significant inter-individual variance. Mothers of 5765 children of
      the Copenhagen Perinatal Cohort (1959-61) recorded 12 developmental milestones
      prospectively during the child's first year of life. Information on possible
      predictors was collected during pregnancy and at follow-up and was categorized
      into the domains: Family background, Pregnancy and delivery, Postnatal
      influences, and Postnatal growth. The domain Pregnancy and delivery contributed
      most of the explained variance in Overall mean of milestones (14.4%), with
      especially gestational age (beta = -0.15; p <= 0.001) and birth weight (beta = 
      0.16; p <= 0.001) being important predictors. CONCLUSION: Several individual
      factors, especially gestational age, birth weight, breastfeeding, having lived in
      a full-time institution, and weight and head increase in the first year, were
      significantly associated with milestone attainment in the first year of life.
      Variables within the domain of Pregnancy and delivery explained the largest
      proportion of variance in milestone attainment compared to the other domains.
      What is known: * Younger age at attainment of motor developmental milestones
      positively predicts cognitive outcomes in adulthood. * Both pre- and postnatal
      factors have been associated with age of attaining milestones in infancy. What is
      new: * First study to provide a systematic evaluation of a broad selection of
      predictors of infant milestone attainment. * Variables within the domain of
      Pregnancy and delivery, especially gestational age and birth weight, explained
      the largest proportion of variance in milestone attainment. * The variance
      explained by the predictors decreased time-dependently with later milestones.

PMID- 27896428
TI  - XCI-escaping gene KDM5C contributes to ovarian development via downregulating miR
      320a.
AB  - Mechanisms underlying female gonadal dysgenesis remain unclarified and relatively
      unstudied. Whether X-chromosome inactivation (XCI)-escaping genes and microRNAs
      (miRNAs) contribute to this condition is currently unknown. We compared 45,X
      Turner Syndrome women with 46,XX normal women, and investigated differentially
      expressed miRNAs in Turner Syndrome through plasma miRNA sequencing. We found
      that miR-320a was consistently upregulated not only in 45,X plasma and peripheral
      blood mononuclear cells (PBMCs), but also in 45,X fetal gonadal tissues. The
      levels of miR-320a in PBMCs from 45,X, 46,XX, 46,XY, and 47,XXY human subjects
      were inversely related to the expression levels of XCI-escaping gene KDM5C in
      PBMCs. In vitro models indicated that KDM5C suppressed miR-320a transcription by
      directly binding to the promoter of miR-320a to prevent histone methylation. In
      addition, we demonstrated that KITLG, an essential gene for ovarian development
      and primordial germ cell survival, was a direct target of miR-320a and that it
      was downregulated in 45,X fetal gonadal tissues. In conclusion, we demonstrated
      that downregulation of miR-320a by the XCI-escaping gene KDM5C contributed to
      ovarian development by targeting KITLG.

PMID- 27896430
TI  - Myosin light chain phosphorylation is required for peak power output of mouse
      fast skeletal muscle in vitro.
AB  - The skeletal myosin light chain kinase (skMLCK) catalyzed phosphorylation of the
      myosin regulatory light chain (RLC) is associated with potentiation of force,
      work, and power in rodent fast twitch muscle. The purpose of this study was to
      compare concentric responses of EDL from wild-type (WT) and skMLCK devoid (skMLCK
      /-) muscles at a range of shortening speeds (0.05 to 0.70 V max) around that
      expected to produce maximal power (in vitro, 25  degrees C) both before
      (unpotentiated) and after (potentiated) a potentiating stimulus (PS). When
      collapsed across all speeds tested, neither unpotentiated force, work, or power
      differed between genotypes (all data n = 10, P < 0.05). In contrast, although
      both genotypes displayed speed-dependent increases, these increases were greater
      for WT than skMLCK-/- muscles. For example, when collapsed across the six fastest
      speeds we tested, both concentric force and power were increased 30-34 % in WT
      but only 15-17 % in skMLCK-/- muscles. In contrast, at the two slowest speeds,
      these parameters were increased in WT but decreased in skMLCK-/- muscles (8-10
      and 7-9 %, respectively). Intriguingly, potentiation of concentric force and
      power was optimal near speeds producing maximal power in both genotypes. Because
      the PS elevated RLC phosphorylation above resting levels in WT but not in skMLCK
      /- muscles, our data suggest that skMLCK-catalyzed phosphorylation of the RLC is
      required for maximal concentric power output of mouse EDL muscle stimulated at
      high frequency in vitro.

PMID- 27896431
TI  - Functional natural allelic variants of flavonoid 3',5'-hydroxylase gene governing
      catechin traits in tea plant and its relatives.
AB  - MAIN CONCLUSION: Functional allelic variants of the flavonoid 3',5'-hydroxylase
      (F3'5'H) gene provides new information of F3'5'H function of tea plant and its
      relatives. This insight may serve as the foundation upon which to advance
      molecular breeding in the tea plant. Catechins are the active components of tea
      that determine its quality and health attributes. This study established the
      first integrated genomic strategy for deciphering the genetic basis of catechin
      traits of tea plant. With the RNA-sequencing analysis of bulked segregants
      representing the tails of a F1 population segregated for total catechin content,
      we identified a flavonoid 3',5'-hydroxylase (F3'5'H) gene. F3'5'H had one copy in
      the genomic DNA of tea plant. Among 202 tea accessions, we identified 120 single
      nucleotide polymorphisms (SNPs) at F3'5'H locus. Seventeen significant marker
      trait associations were identified by association mapping in multiple
      environments, which were involved in 10 SNP markers, and the traits including the
      ratio of di/tri-hydroxylated catechins and catechin contents. The associated
      individual and combination of SNPs explained 4.5-25.2 and 53.0-63.0% phenotypic
      variations, respectively. In the F1 population (validation population), the
      catechin trait variation percentages explained by F3'5'H diplotype were 6.9
      74.3%. The genotype effects of ten functional SNPs in the F1 population were all
      consistent with the association population. Furthermore, the function of SNP-711/
      655 within F3'5'H was validated by gene expression analysis. Altogether, our work
      indicated functional SNP allelic variants within F3'5'H governing the ratio of
      di/tri-hydroxylated catechins and catechin contents. The strong catechin
      associated SNPs identified in this study can be used for future marker-assisted
      selection to improve tea quality.

PMID- 27896433
TI  - Continuous daily assessment of multiple sclerosis disability using remote step
      count monitoring.
AB  - Disability measures in multiple sclerosis (MS) rely heavily on ambulatory
      function, and current metrics fail to capture potentially important variability
      in walking behavior. We sought to determine whether remote step count monitoring
      using a consumer-friendly accelerometer (Fitbit Flex) can enhance MS disability
      assessment. 99 adults with relapsing or progressive MS able to walk >=2-min were
      prospectively recruited. At 4 weeks, study retention was 97% and median Fitbit
      use was 97% of days. Substudy validation resulted in high interclass correlations
      between Fitbit, ActiGraph and manual step count tally during a 2-minute walk
      test, and between Fitbit and ActiGraph (ICC = 0.76) during 7-day home monitoring.
      Over 4 weeks of continuous monitoring, daily steps were lower in progressive
      versus relapsing MS (mean difference 2546 steps, p < 0.01). Lower average daily
      step count was associated with greater disability on the Expanded Disability
      Status Scale (EDSS) (p < 0.001). Within each EDSS category, substantial
      variability in step count was apparent (i.e., EDSS = 6.0 range 1097-7152). Step
      count demonstrated moderate-strong correlations with other walking measures.
      Lower average daily step count is associated with greater MS disability and
      captures important variability in real-world walking activity otherwise masked by
      standard disability scales, including the EDSS. These results support remote step
      count monitoring as an exploratory outcome in MS trials.

PMID- 27896434
TI  - Towards a functional pathology of hereditary neuropathies.
AB  - A growing number of hereditary neuropathies have been assigned to causative gene
      defects in recent years. The study of human nerve biopsy samples has contributed
      substantially to the discovery of many of these neuropathy genes. Genotype
      phenotype correlations based on peripheral nerve pathology have provided a
      comprehensive picture of the consequences of these mutations. Intriguingly,
      several gene defects lead to distinguishable lesion patterns that can be studied
      in nerve biopsies. These characteristic features include the loss of certain
      nerve fiber populations and a large spectrum of distinct structural changes of
      axons, Schwann cells and other components of peripheral nerves. In several
      instances the lesion patterns are directly or indirectly linked to the known
      functions of the mutated gene. The present review is designed to provide an
      overview on these characteristic patterns. It also considers other aspects
      important for the manifestation and pathology of hereditary neuropathies
      including the role of inflammation, effects of chemotherapeutic agents and
      alterations detectable in skin biopsies.

PMID- 27896429
TI  - Copy number variability in Parkinson's disease: assembling the puzzle through a
      systems biology approach.
AB  - Parkinson's disease (PD), the second most common progressive neurodegenerative
      disorder of aging, was long believed to be a non-genetic sporadic origin
      syndrome. The proof that several genetic loci are responsible for rare Mendelian
      forms has represented a revolutionary breakthrough, enabling to reveal molecular
      mechanisms underlying this debilitating still incurable condition. While single
      nucleotide polymorphisms (SNPs) and small indels constitute the most commonly
      investigated DNA variations accounting for only a limited number of PD cases,
      larger genomic molecular rearrangements have emerged as significant PD-causing
      mutations, including submicroscopic Copy Number Variations (CNVs). CNVs
      constitute a prevalent source of genomic variations and substantially participate
      in each individual's genomic makeup and phenotypic outcome. However, the majority
      of genetic studies have focused their attention on single candidate-gene
      mutations or on common variants reaching a significant statistical level of
      acceptance. This gene-centric approach is insufficient to uncover the genetic
      background of polygenic multifactorial disorders like PD, and potentially masks
      rare individual CNVs that all together might contribute to disease development or
      progression. In this review, we will discuss literature and bioinformatic data
      describing the involvement of CNVs on PD pathobiology. We will analyze the most
      frequent copy number changes in familiar PD genes and provide a "systems biology"
      overview of rare individual rearrangements that could functionally act on
      commonly deregulated molecular pathways. Assessing the global genome-wide burden
      of CNVs in PD patients may reveal new disease-related molecular mechanisms, and
      open the window to a new possible genetic scenario in the unsolved PD puzzle.

PMID- 27896432
TI  - Repression of telomere-associated genes by microglia activation in
      neuropsychiatric disease.
AB  - Microglia senescence may promote neuropsychiatric disease. This prompted us to
      examine the relationship between microglia activation states and telomere
      biology. A panel of candidate genes associated with telomere maintenance,
      mitochondrial biogenesis, and cell-cycle regulation were investigated in M1- and
      M2-polarized microglia in vitro as well as in MACS-purified CD11b+
      microglia/brain macrophages from models of stroke, Alzheimer's disease, and
      chronic stress. M1 polarization, ischemia, and Alzheimer pathology elicited a
      strikingly similar transcriptomic profile with, in particular, reduced expression
      of murine Tert. Our results link classical microglia activation with repression
      of telomere-associated genes, suggesting a new mechanism underlying microglia
      dysfunction.

PMID- 27896435
TI  - Course of pelvic lift during total hip arthroplasty.
AB  - INTRODUCTION: The position of the cup makes a major contribution to the success
      of total hip arthroplasty (THA). In conventional implantation of the prosthesis
      without navigation, the surgeon relies on the spatial position of the pelvis.
      However, iatrogenic manipulation of the pelvis during different surgical steps
      constantly changes the position of the pelvis during the operation. The position
      of the pelvis is substantial for the correct placement of the cup. The objective
      of this study was to investigate and visualize the course of this pelvic lift and
      correlate it to certain surgical steps. MATERIALS AND METHODS: Pelvic lift was
      measured in 67 patients during implantation of a THA. This was done by measuring
      acceleration using the SensorLog app on a smartphone. It was placed on the
      patient's contralateral anterior superior iliac spine and recorded the movement
      of the pelvis throughout the whole surgical procedure. The position of the pelvis
      was allocated to each of eight relevant surgical steps during the operation.
      These surgical steps were normed over the time axis and transferred to a diagram.
      RESULTS: We found an average pelvic lift displacement of up to 14.9 degrees  upon
      placement in the figure-of-four position. This lift is particularly critical when
      exposing the acetabulum, as the true cup position can be unconsciously
      influenced. Average values of between 5.6 degrees  and 6.9 degrees  were found
      here. CONCLUSIONS: When implanting a THA in supine position, the pelvis is not
      fixed on the operating table. Rather, the side to be operated on is lifted to a
      greater or lesser degree, depending on the surgical step to be performed. The
      retractor traction immediately before cup implantation should be minimized.
      Nevertheless, it should be taken into account that anteversion of the cup implant
      in relation to the table plane is systematically higher than in relation to the
      pelvic entry plane.

PMID- 27896436
TI  - Risk factors for complications after adrenalectomy: results from a comprehensive
      national database.
AB  - PURPOSE: Most knowledge regarding outcome after adrenal surgery stems from
      retrospective studies reported by highly specialized centres. The aim of this
      study was to report a national experience of adrenalectomy with particular
      attention to predictive factors for postoperative complications, conversion from
      endoscopic to open surgery and length of hospital stay. METHODS: Adrenalectomies
      reported in the Scandinavian Quality Register for Thyroid, Parathyroid and
      Adrenal Surgery (SQRTPA) 2009-2014 were included. Risk factors for complications,
      conversion and hospital stay >3 days were assessed using univariable and
      multivariable logistic regression analysis. RESULTS: There were 659 operations.
      Endoscopic adrenalectomy was performed in 513 (77.8%) operations and almost half
      of these were robotic assisted. The median length of hospital stay was 3 (range 1
      30) days. There was no 30-day mortality. In 43 (6.6%) patients, at least one
      complication was registered. The only factor associated with complications in
      multivariable analysis was conversion to open surgery odds ratio (OR) 3.61 (95%
      confidence interval 1.07 to 12.12). The risk for conversion was associated with
      tumour size OR 1.03 (1.00 to 1.06) and with malignancy on histopathology OR 8.33
      (2.12 to 32.07). Length of hospital stay increased in patients with operation of
      bilateral tumours OR 3.13, left-sided tumours OR 1.98, hyper secretion of
      catecholamines OR 2.32, conversion to open surgery OR 42.05 and open surgery OR
      115.18. CONCLUSIONS: The present study shows that endoscopic surgery is widely
      used. Complications were associated with conversion and the risk for conversion
      was associated with tumour size and malignant tumour. Hospital stay was short.

PMID- 27896437
TI  - [Inflammatory myopathies].
AB  - Inflammatory myopathies comprise heterogeneous, often multisystemic autoimmune
      diseases with muscle involvement as a common feature. The prognosis largely
      depends on a timely diagnosis and initiation of therapy. Given the complexity of
      these rare diseases, when an inflammatory myopathy is suspected patients should
      be referred to an expert center with established algorithms for the diagnostic
      work-up. The differential diagnostic exclusion of myositis mimics should ideally
      be carried out in close collaboration with neurologists and neuropathologists.
      The choice of immunosuppressive treatment should primarily depend on disease
      severity and organ involvement but age and comorbidities also have to be taken
      into account.

PMID- 27896438
TI  - Survival of a recessive allele in a Mendelian diploid model.
AB  - In this paper we analyse the genetic evolution of a diploid hermaphroditic
      population, which is modelled by a three-type nonlinear birth-and-death process
      with competition and Mendelian reproduction. In a recent paper, Collet et al. (J
      Math Biol 67(3):569-607, 2013) have shown that, on the mutation time-scale, the
      process converges to the Trait-Substitution Sequence of adaptive dynamics,
      stepping from one homozygotic state to another with higher fitness. We prove
      that, under the assumption that a dominant allele is also the fittest one, the
      recessive allele survives for a time of order at least [Formula: see text], where
      K is the size of the population and [Formula: see text].

PMID- 27896440
TI  - A phase III, open label, randomized multicenter controlled trial of oral versus
      intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of
      the North-Eastern German Society of Gynecological Oncology (NOGGO).
AB  - OBJECTIVE: In recurrent ovarian cancer (ROC), there is a high demand on effective
      therapies with a mild toxicity profile. Treosulfan is an alkylating agent
      approved as oral (p.o.) and intravenous (i.v.) formulation for the treatment of
      recurrent ovarian cancer. Data on safety and efficacy for either formulation are
      rare. For the first time we conducted a randomized phase III study comparing both
      formulations in women with ROC. METHODS: Patients having received at least two
      previous lines of chemotherapy were randomly assigned to one of two treatment
      arms: treosulfan i.v. 7000 mg/m2 d1 q4w or treosulfan p.o. 600 mg/m2 d1-28 q8w.
      Primary endpoint was safety regarding hematological and gastrointestinal toxicity
      grade III/IV, secondary endpoints were other toxicities, clinical benefit rate
      (CBR), time to progression (TTP), overall survival (OS) and quality of life.
      RESULTS: 250 patients were treated with treosulfan i.v. (128) or treosulfan p.o.
      (122). In general treosulfan therapy was well tolerated in both treatment arms.
      Leukopenia grade III/IV occurred significantly more frequently in the p.o. arm
      (3.9% i.v. arm, 14.8% p.o. arm, p = 0.002). Other toxicities were similar in both
      arms. CBR was comparable between arms (41.4% i.v. arm, 36.9% p.o. arm). No
      difference in TTP (3.7 months i.v. arm, 3.5 months p.o. arm) or OS (13.6 months
      i.v. arm, 10.4 months p.o. arm, p = 0.087) occurred. CONCLUSIONS: Given the
      safety and efficacy results treosulfan is an acceptable option for heavily
      pretreated OC patients. Regarding the toxicity profile the i.v. application was
      better tolerated with less grade III and IV toxicities.

PMID- 27896439
TI  - Characterization of pollen-expressed bZIP protein interactions and the role of
      ATbZIP18 in the male gametophyte.
AB  - KEY MESSAGE : bZIP TF network in pollen. Transcriptional control of gene
      expression represents an important mechanism guiding organisms through
      developmental processes and providing plasticity towards environmental stimuli.
      Because of their sessile nature, plants require effective gene regulation for
      rapid response to variation in environmental and developmental conditions.
      Transcription factors (TFs) provide such control ensuring correct gene expression
      in spatial and temporal manner. Our work reports the interaction network of six
      bZIP TFs expressed in Arabidopsis thaliana pollen and highlights the potential
      functional role for AtbZIP18 in pollen. AtbZIP18 was shown to interact with three
      other pollen-expressed bZIP TFs-AtbZIP34, AtbZIP52, and AtbZIP61 in yeast two
      hybrid assays. AtbZIP18 transcripts are highly expressed in pollen, and at the
      subcellular level, an AtbZIP18-GFP fusion protein was located in the nucleus and
      cytoplasm/ER. To address the role of AtbZIP18 in the male gametophyte, we
      performed phenotypic analysis of a T-DNA knockout allele, which showed slightly
      reduced transmission through the male gametophyte. Some of the phenotype defects
      in atbzip18 pollen, although observed at low penetrance, were similar to those
      seen at higher frequency in the T-DNA knockout of the interacting partner,
      AtbZIP34. To gain deeper insight into the regulatory role of AtbZIP18, we
      analysed atbzip18/- pollen microarray data. Our results point towards a potential
      repressive role for AtbZIP18 and its functional redundancy with AtbZIP34 in
      pollen.

PMID- 27896441
TI  - Pterygium surgery using the principle of contact inhibition: results of 13 years'
      experience.
AB  - PURPOSE: To report a technique to prevent pterygium recurrence using the
      principle of contact inhibition. METHODS: Two hundred and fifteen patients (232
      eyes; average age, 64.1 years) with primary pterygia who underwent pterygium
      surgery at the Hara Eye Hospital between 1999 and 2012. We retrospectively
      evaluated the patients who underwent the following procedure to prevent pterygium
      recurrence. The surface conjunctiva on the pterygium body was not removed. After
      removing the pterygium body, by placing a narrow pedicle autoconjunctival flap
      along the corneal limbus and tying it tightly to the front area of the residual
      conjunctiva, there is no room for the active residual tissue to proliferate, thus
      preventing a recurrence by contact inhibition. The key factor is conjunctival
      suturing, which establishes face-to-face contact of both areas of cut
      conjunctival tissue. Mitomycin C is applied locally for 3 min intraoperatively
      and 5 days postoperatively. The main outcome measure was the prevention of
      pterygium recurrence using this technique. RESULTS: By the end of the average
      follow-up of 5 years 4 months, three eyes (1.3%) had a recurrence. Among the 232
      eyes, 23 eyes had large pterygia extending to the pupillary area. Using the
      surgical technique, there were no recurrences. No specific characteristic of the
      recurrence was found in association with the eye, sex, and preoperative grade.
      CONCLUSIONS: This surgery has three relevant features: (1) reconfirmation of the
      effect of contact inhibition, (2) the anatomic structure of the conjunctival sac
      scarcely changes postoperatively, because the surface conjunctiva of the
      pterygium body is not removed, and (3) a low recurrence rate.

PMID- 27896442
TI  - Regional citrate anticoagulation for continuous renal replacement therapy in
      children.
AB  - BACKGROUND: Anticoagulation of the continuous renal replacement therapy (CRRT)
      circuit is an important technical aspect of this medical procedure. Most studies
      evaluating the efficacy and safety of citrate use have been carried out in
      adults, and little evidence is available for the pediatric patient population.
      The aim of this study was to compare regional citrate anticoagulation versus
      systemic heparin anticoagulation in terms of the lifetime of hemofilters in a
      pediatric population receiving CRRT at a pediatric center in Bogota, Colombia.
      METHODS: This was an analytical, observational, retrospective cohort study in
      which we assessed the survival of 150 hemofilters (citrate group 80 hemofilters,
      heparin group 70 hemofilters) used in a total of 3442 hours of CCRT (citrate
      group 2248 h, heparin group 1194 h). Hemofilter survival was estimated beginning
      at placement and continuing until filter replacement due to clotting or high
      trans-membrane pressures. RESULTS: Hemofilter survival was higher in the citrate
      group than in the heparin group (72 vs. 18 h; p <0.0001). Bivariate analysis
      showed that the hemofilter coagulation risk was significantly increased when
      heparin was used, regardless of hemofilter size and pump flow (hazard ratio 3.70,
      standard error 0.82, 95% confidence interval 2.39-5.72; p <0.00001). CONCLUSIONS:
      Regional citrate anticoagulation could be more effective than heparin systemic
      anticoagulation in terms of prolonging the hemofilter lifetime in patients with
      acute renal injury who require CRRT.

PMID- 27896444
TI  - Is all hypoglycaemia treated as equal? An observational study of how the type of
      diabetes and treatment prescribed prior to admission influences quality of
      treatment of inpatient hypoglycaemia.
AB  - AIMS: Inpatient hypoglycaemia is common and associated with adverse outcomes.
      There is often increased vigilance of hypoglycaemia in inpatients with type 1
      diabetes (T1DM) compared to type 2 diabetes (T2DM). We aimed to investigate this
      apparent discrepancy, utilising the time to repeat (TTR) capillary blood glucose
      (CBG) measurement as a surrogate for engagement with guidelines stating that CBG
      should be rechecked following intervention within 15 min of an initial CBG of <4
      mmol/L. METHODS: This is an observational study of inpatient CBG data from 8
      hospitals over a 7-year period. A national diabetes registry allowed
      identification of individual's diagnosis and diabetes therapy. For each initial
      (index) CBG, the TTR for individuals with T2DM-on insulin or sulphonylurea-was
      compared with the TTR for individuals with T1DM, using a t test for significance
      performed on log(TTR). The median TTR was plotted for each group per index CBG.
      RESULTS: In total, 1480,335 CBG measurements were obtained. A total of 26,664
      were <4 mmol/L. The TTR in T2DM individuals on sulphonylurea was significantly
      greater than in T1DM individuals where index CBG was >=2.3 mmol/L (except index
      CBG 2.6 mmol/L). For T2DM patients receiving insulin significance exists for
      index CBGs of >=3.2 mmol/L. CONCLUSIONS: This analysis suggests that quality of
      care of hypoglycaemia varies according to diagnosis and medication. The group
      with the highest TTR (T2DM sulphonylurea treated) are possibly the clinical group
      in whom hypoglycaemia is most concerning. These data therefore suggest a need for
      education and raising awareness within the inpatient nursing staff.

PMID- 27896443
TI  - Dietary sources of sugars in adolescents' diet: the HELENA study.
AB  - OBJECTIVE: To report dietary sugars consumption and their different types and
      food sources, in European adolescents. METHODS: Food consumption data of selected
      groups were obtained from 1630 adolescents (45.6% males, 12.5-17.5 years) from
      the HELENA study using two nonconsecutive 24-h recalls. Energy intake, total
      sugars and free sugars were assessed using the HELENA-DIAT software. Multiple
      regression analyses were performed adjusting for relevant confounders. RESULTS:
      Total sugars intake (137.5 g/day) represented 23.6% and free sugars (110.1
      g/day), 19% of energy intake. Girls had significantly lower intakes of energy,
      carbohydrates, total sugars and free sugars. 94% of adolescents had a consumption
      of free sugars above 10% of total energy intake. The main food contributor to
      free sugars was 'carbonated, soft and isotonic drinks,' followed by 'non
      chocolate confectionary' and 'sugar, honey, jam and syrup.' Older boys and girls
      had significantly higher intakes of free sugars from 'cakes, pies and biscuits.'
      Free sugars intake was negatively associated with low socioeconomic status for
      'non-chocolate confectionary' and 'sugar, honey and jam' groups; with low
      maternal educational level for carbonated and 'soft drinks,' 'sugar, honey and
      jam,' 'cakes and pies' and 'breakfast cereals' groups; and with high paternal
      educational level for 'carbonated and soft drinks' and 'chocolates' group.
      CONCLUSIONS: The majority (94%) of studied adolescents consumed free sugars above
      10% of daily energy intake. Our data indicate a broad variety in foods providing
      free sugars. Continued efforts are required at different levels to reduce the
      intake of free sugars, especially in families with a low educational level.

PMID- 27896446
TI  - Biocompatible silver nanoparticles prepared with amino acids and a green method.
AB  - The synthesis of nanoparticles is usually carried out by chemical reduction,
      which is effective but uses many toxic substances, making the process potentially
      harmful to the environment. Hence, as part of the search for environmentally
      friendly or green synthetic methods, this study aimed to produce silver
      nanoparticles (AgNPs) using only AgNO3, Milli-Q water, white light from a xenon
      lamp (Xe) and amino acids. Nanoparticles were synthetized using 21 amino acids,
      and the shapes and sizes of the resultant nanoparticles were evaluated. The
      products were characterized by UV-Vis, zeta potential measurements and
      transmission electron microscopy. The synthesis of silver nanoparticles with
      tryptophan and tyrosine, methionine, cystine and histidine was possible through
      photoreduction method. Spherical nanoparticles were produced, with sizes ranging
      from 15 to 30 nm. Tryptophan does not require illumination nor heating, and the
      solution color changes immediately after the mixing of reagents if sodium
      hydroxide is added to the solution (pH = 10). The Xe illumination acts as sodium
      hydroxide in the nanoparticles synthesis, releases H+ and allows the reduction of
      silver ions (Ag+) in metallic silver (Ag0).

PMID- 27896445
TI  - Serum 1,5-anhydroglucitol level as a screening tool for diabetes mellitus in a
      community-based population at high risk of diabetes.
AB  - AIMS: Early diagnosis of diabetes yields significant clinical benefits; however,
      currently available diagnostic tools for community-based population are limited.
      This study aimed to assess the value of serum 1,5-anhydroglucitol (1,5-AG) for
      the diagnosis and screening of diabetes mellitus in a community-based population
      at high risk of diabetes. METHODS: In this diagnostic test, 1170 participants
      underwent a 75-g oral glucose tolerance test. Venous blood samples were collected
      for fasting blood glucose (FBG), 2-h postprandial blood glucose (PBG), and
      glycosylated hemoglobin A1c (HbA1c) measurements. Serum 1,5-AG levels were
      detected by the GlycoMark assay, and a receiver operating characteristic (ROC)
      curve was generated to assess their diagnostic value for diabetes. RESULTS: A
      total of 298 adults were diagnosed with diabetes, indicating a prevalence of
      25.47%. Partial Pearson correlation analysis adjusted for age and body mass index
      showed that serum 1,5-AG level was negatively correlated with FBG, PBG, and HbA1c
      (all P < 0.01). Areas under the curves (AUCs) for serum 1,5-AG, FBG, PBG, and
      HbA1c in identifying diabetes were 0.920, 0.874, 0.933, and 0.887, respectively.
      According to the ROC curve, the optimal cutoff value of serum 1,5-AG for
      diagnosing diabetes was 11.18 MUg/ml, which yielded a sensitivity of 92.6% and a
      specificity of 82.3%, respectively. Comparisons between 1,5-AG and HbA1c showed
      that both the AUC and sensitivity of 1,5-AG were higher than those of HbA1c (both
      P < 0.01). CONCLUSIONS: Serum 1,5-AG is a simple and effective marker with high
      sensitivity and specificity for identifying diabetes in populations at high risk
      of diabetes.

PMID- 27896447
TI  - Novel "extended sequons" of human N-glycosylation sites improve the precision of
      qualitative predictions: an alignment-free study of pattern recognition using
      ProtDCal protein features.
AB  - N-Glycosylation is a common post-translational modification that plays an
      important role in the proper folding and function of many proteins. This
      modification is largely dependent on the presence of a sequence motif called a
      "sequon" defined as Asn-Xxx-Ser/Thr. However, evidence has shown that the
      presence of such a "sequon" is insufficient to determine the occurrence of N
      glycosylation with high precision. This study aims to elucidate patterns that can
      more accurately predict N-glycosylation sites in human proteins. The novel motifs
      are evaluated using benchmarking data from 188 organisms. Performance is largely
      sustained compared to the human data, which validates the robustness of the novel
      extracted "extended sequons". We, therefore, introduce new knowledge about
      sequence-related factors that control N-glycosylation.

PMID- 27896448
TI  - ?

PMID- 27896449
TI  - ?

PMID- 27896451
TI  - Transfer Learning with Convolutional Neural Networks for Classification of
      Abdominal Ultrasound Images.
AB  - The purpose of this study is to evaluate transfer learning with deep
      convolutional neural networks for the classification of abdominal ultrasound
      images. Grayscale images from 185 consecutive clinical abdominal ultrasound
      studies were categorized into 11 categories based on the text annotation
      specified by the technologist for the image. Cropped images were rescaled to 256
      * 256 resolution and randomized, with 4094 images from 136 studies constituting
      the training set, and 1423 images from 49 studies constituting the test set. The
      fully connected layers of two convolutional neural networks based on CaffeNet and
      VGGNet, previously trained on the 2012 Large Scale Visual Recognition Challenge
      data set, were retrained on the training set. Weights in the convolutional layers
      of each network were frozen to serve as fixed feature extractors. Accuracy on the
      test set was evaluated for each network. A radiologist experienced in abdominal
      ultrasound also independently classified the images in the test set into the same
      11 categories. The CaffeNet network classified 77.3% of the test set images
      accurately (1100/1423 images), with a top-2 accuracy of 90.4% (1287/1423 images).
      The larger VGGNet network classified 77.9% of the test set accurately (1109/1423
      images), with a top-2 accuracy of VGGNet was 89.7% (1276/1423 images). The
      radiologist classified 71.7% of the test set images correctly (1020/1423 images).
      The differences in classification accuracies between both neural networks and the
      radiologist were statistically significant (p < 0.001). The results demonstrate
      that transfer learning with convolutional neural networks may be used to
      construct effective classifiers for abdominal ultrasound images.

PMID- 27896450
TI  - Extremity CTA for penetrating trauma: 10-year experience using a 64-detector row
      CT scanner.
AB  - PURPOSE: The purpose of this study is to assess the performance of CT angiography
      (CTA) in the evaluation of penetrating vascular trauma to the extremities in a
      large cohort of patients at our level I trauma center. METHODS: A retrospective,
      IRB-approved review of consecutive CTAs for the evaluation of penetrating trauma
      to the extremities in 446 patients (M/F = 396:50, mean age = 27 years) from
      1/1/2005 to 5/1/2015 was performed. Medical records were reviewed to correlate
      diagnostic imaging findings with clinical history and subsequent interventions.
      Image quality was quantified by measurement of CT attenuation coefficients in the
      major arteries of the extremities. The Fisher's exact test was used to analyze
      the relationships between the presence and type of vascular injury and subsequent
      clinical management. RESULTS: One hundred and thirty-one (29.4 %) of 446 patients
      with penetrating trauma demonstrated major vascular injury on CTA, 35 (26.7 %) of
      whom underwent subsequent surgical repair. None of the patients without vascular
      injury on CTA underwent subsequent vascular intervention. Fisher's exact test
      demonstrated a statistically significant difference in management and requirement
      for vascular repair in those patients with a vascular injury on CTA when compared
      to those without a vascular injury (p < 0.0001). The mean attenuation values
      achieved in upper and lower extremity CTAs in this population exceeded 250 HU.
      CONCLUSION: Extremity CTA is found to be an accurate tool for surgical triage in
      patients having sustained penetrating vascular trauma.

PMID- 27896452
TI  - Optimization of Image Quality and Dose in Digital Mammography.
AB  - Nowadays, the optimization in digital mammography is one of the most important
      challenges in diagnostic radiology. The new digital technology has introduced
      additional elements to be considered in this scenario. A major goal of
      mammography is related to the detection of structures on the order of micrometers
      (MUm) and the need to distinguish the different types of tissues, with very close
      density values. The diagnosis in mammography faces the difficulty that the breast
      tissues and pathological findings have very close linear attenuation coefficients
      within the energy range used in mammography. The aim of this study was to develop
      a methodology for optimizing exposure parameters of digital mammography based on
      a new Figure of Merit: FOM = (IQFinv)2/AGD, considering the image quality and
      dose. The study was conducted using the digital mammography Senographe DS/GE, and
      CDMAM and TORMAM phantoms. The characterization of clinical practice, carried out
      in the mammography system under study, was performed considering different breast
      thicknesses, the technical parameters of exposure, and processing options of
      images used by the equipment's automatic exposure system. The results showed a
      difference between the values of the optimized parameters and those ones chosen
      by the automatic system of the mammography unit, specifically for small breast.
      The optimized exposure parameters showed better results than those obtained by
      the automatic system of the mammography, for the image quality parameters and its
      impact on detection of breast structures when analyzed by radiologists.

PMID- 27896454
TI  - Venous air embolism in the sitting position in cranial neurosurgery: incidence
      and severity according to the used monitoring.
AB  - BACKGROUND: There is an ongoing debate about the sitting position (SP) in
      neurosurgical patients. The SP provides a number of advantages as well as severe
      complications such as commonly concerning venous air embolism (VAE). The best
      monitoring system for the detection of VAE is still controversial. METHODS: In
      this retrospective analysis we compared 208 patients. Transesophageal
      echocardiography (TEE) or transthoracic Doppler (TTD) were used as monitoring
      devices to detect VAE; 101 cases were monitored with TEE and 107 with TTD.
      RESULTS: The overall incidence of VAE was 23% (TTD: 10%; TEE: 37%), but the
      incidence of clinically relevant VAE (drop in end-tidal carbon dioxide above 3
      mmHg) was higher in the TTD group (9 out of 17 VAE, 53%) compared to the TEE
      group (19 out of 62 VAE, 31%). None of the patients with recorded VAE had
      clinically significant sequelae. CONCLUSIONS: In this small sample we found more
      VAE events in the TEE group, but the incidence of clinically relevant VAE was
      rare and comparable to other data. There is no consensus in the definition of
      clinically relevant VAE.

PMID- 27896455
TI  - Erratum to: Tachycardia detection in modern implantable cardioverter
      defibrillators.

PMID- 27896453
TI  - Management of phosphorus load in CKD patients.
AB  - Disturbances in mineral and bone metabolism play a critical role in the
      pathogenesis of cardiovascular complications in patients with chronic kidney
      disease (CKD). The term "renal osteodystrophy" has recently been replaced with
      "CKD-mineral and bone disorder (CKD-MBD)", which includes vascular calcification
      as well as bone abnormalities. In Japan, proportions of the aged and long-term
      dialysis patients are increasing which makes management of vascular calcification
      and parathyroid function increasingly more important. There are three main
      strategies to manage phosphate load: phosphorus dietary restriction,
      administration of phosphate binder and to ensure in the CKD 5D setting, an
      adequate dialysis.

PMID- 27896456
TI  - DNA copy number profiling in microsatellite-stable and microsatellite-unstable
      hereditary non-polyposis colorectal cancers by targeted CNV array.
AB  - About half of hereditary non-polyposis colorectal cancers (HNPCCs) fulfilling the
      Amsterdam criteria (AC) do not display evidence of mismatch repair defects, and
      the difference between microsatellite-stable (MSS) and microsatellite-unstable
      HNPCC remains poorly understood. The study was to compare overall copy number
      variation (CNV) and loss of heterozygosity (LOH) of the entire genome in HNPCCs
      with MSS and microsatellite-instability (MSI) using the Cytoscan HD Array. This
      was a study carried out in samples from 20 patients with MSS HNPCC and four
      patients with MSI HNPCC from the Fudan University Shanghai Cancer Center (China).
      The microsatellite status was examined using a panel of microsatellite markers.
      MMR expression status was evaluated by immunohistochemistry. Tumor samples were
      analyzed with the Genome-Wide Human CytoScan HD Array. CNV and LOH were
      determined. Fourteen specific CNVs (eight gains: 5p13.1, 7p13, 7q22.3, 8q11.21,
      8q12.2, 19q13.11, 20q11.21, and 20q11.23; and six losses: 8p22, 8p23.1, 8p23.1,
      17p13.1, 17p13.2, and 18q21.3) were associated with MSS HNPCC. Of these 14 CNVs,
      gain on 8q12.2 and loss on 17p13.1 were novel. The total length of 8q gains and
      20q gains were greater in MSS tumors than in MSI (P < 0.05). The presence of
      similar levels of copy-neutral-LOH in MSS (31.7%) and MSI (29.7%) HNPCC suggested
      that unknown DNA repair genes might be involved in the tumorigenesis of MSS
      HNPCC. MSS HNPCC is a genetically specific population with increased CNV, which
      are different from MSI HNPCC. The results may help to clarify the genetic basis
      of MSS HNPCC tumorigenesis.

PMID- 27896457
TI  - The value of quantitative sensory testing in spine research.
AB  - The improvement of pain and functionality is the major goal of a surgical
      intervention. Thus, the purpose of the present prospective study was to evaluate
      whether subjective sensory deficits in patients with lumbar radiculopathy caused
      by a lumbar disc herniation are related to clinical status, using several outcome
      scores and the quantitative sensory testing (QST) pre- and 12 months
      postoperatively. We applied the QST in 52 patients with a single lumbar disc
      herniation treated by lumbar sequestrectomy pre- and 12 months postoperatively.
      Further evaluation included numeric rating scale (NRS) for leg, EuroQoL-5D (EQ
      5D), Core Outcome Measure Index (COMI), Oswestry Disability Index (ODI), Beck
      Depression Inventory (BDI) and PaindDetect questionnaire (PD-Q). Patients were
      then categorized into two groups based on their subjective recovery of sensory
      function. The patients' self-assessment and QST were correlated with each other
      for the pre- and postoperative visit after 12 months. The two groups showed
      postoperative differences in mechanical and vibration detection threshold as well
      as in the postoperative PD-Q (p < 0.005). Multidimensional scores did not
      consistently match the QST parameters in patients with a lumbar disc herniation.
      Commonly used clinical scores in spine research show low or no correlation with
      QST. Nevertheless, mechanical thresholds seem to play an important role to detect
      and follow up a sensory deficit investigated by QST.

PMID- 27896459
TI  - Gluteal transposition flap without donor site scar for closing a perineal defect
      after abdominoperineal resection.

PMID- 27896458
TI  - Prognostic factors in the treatment of carpal scaphoid non-unions.
AB  - In this literature review, the authors analyse the prognostic factors in the
      curative treatment of scaphoid non-unions. The main negative prognostic factors
      are smoking, the time elapsed since the fracture, and avascular necrosis of the
      proximal fragment. If the latter is present, the revascularization by a pedicle
      or microsurgical bone autograft is probably the treatment of choice. In non
      unions without evidence of osteonecrosis, vascularized bone grafts are probably
      not superior to conventional bone grafts, which can presently be performed under
      arthroscopic control, with minimal morbidity.

PMID- 27896460
TI  - New-onset rectoanal intussusceptions after laparoscopic ventral rectopexy: a
      normal image?

PMID- 27896462
TI  - With gratitude for the Journal of Plant Research.

PMID- 27896461
TI  - Transversus abdominis plane block for postoperative pain relief after hand
      assisted laparoscopic colon surgery: a randomized, placebo-controlled clinical
      trial.
AB  - BACKGROUND: Although hand-assisted laparoscopic surgery (HALS) offers patients
      smaller surgical incisions, they still experience pain. Currently, there is no
      consensus on the optimal analgesic package for patients undergoing HALS. The aim
      of this prospective, randomized, double-blinded, placebo-controlled clinical
      trial was to evaluate the effect of transversus abdominis plane (TAP) block on
      postoperative pain control (pain score and analgesic use) and other outcomes in
      colon cancer patients undergoing hand-assisted laparoscopic left hemicolectomy.
      METHODS: Sixty-four patients with colon cancer scheduled for an elective colon
      resection were enrolled in this study. Patients were randomized into two groups
      to receive either TAP block using 20 mL of 0.375% ropivacaine (TAP block group:
      32 patients) or 20 mL of 0.9% normal saline infusion (placebo group: 32
      patients). Anaesthetic and surgical techniques were standardized. Twenty-four
      hour postoperative analgesia was maintained by continuous infusion of 0.1-0.9
      ug/kg/h fentanyl and intravenous injection of ketorolac. The primary outcome of
      the study was postoperative pain control (pain score and analgesic use). Pain was
      assessed using numeric rating scale at 2, 4, 8, 12, and 24 h after surgery at
      rest and during movement. Secondary outcomes included the time to resumption of
      intestinal function and the length of hospital stay. The data of the two groups
      were compared using Mann-Whitney U test. All statistical tests were two-tailed at
      a significance level of 0.05. RESULTS: The patients' mean age was 60.50 +/- 6.77
      years, and 68.75% of patients were males. The mean body mass index was 26.23 +/-
      4.83 kg/m2. The TAP block group had lower pain scores after surgery at 2, 4, and
      12 h at rest (p < 0.05), at 2 and 4 h during movement (p < 0.01) and used less
      fentanyl and ketorolac than the placebo group (p < 0.01). The mean time to
      resumption of intestinal function was shorter in the TAP block group than that in
      the placebo group (p < 0.0001). The mean length of hospital stay was by 2.7 days
      shorter in the TAP block group than in the placebo group (p = 0.001).
      CONCLUSIONS: The ultrasound-guided TAP block given during hand-assisted
      laparoscopic colon surgery as part of a multimodal analgesic regimen is a
      feasible and effective technique for postoperative analgesia in colon cancer
      patients and significantly reduces both pain experienced by patients and short
      term postoperative analgesic use and promotes early ambulation. Future studies
      are needed to determine the efficacy and costs/benefits of the ultrasound-guided
      TAP block in HALS.

PMID- 27896463
TI  - Litter mixture dominated by leaf litter of the invasive species, Flaveria
      bidentis, accelerates decomposition and favors nitrogen release.
AB  - In natural ecosystems, invasive plant litter is often mixed with that of native
      species, yet few studies have examined the decomposition dynamics of such
      mixtures, especially across different degrees of invasion. We conducted a 1-year
      litterbag experiment using leaf litters from the invasive species Flaveria
      bidentis (L.) and the dominant co-occurring native species, Setaria viridis (L.).
      Litters were allowed to decompose either separately or together at different
      ratios in a mothproof screen house. The mass loss of all litter mixtures was non
      additive, and the direction and strength of effects varied with species ratio and
      decomposition stage. During the initial stages of decomposition, all mixtures had
      a neutral effect on the mass loss; however, at later stages of decomposition,
      mixtures containing more invasive litter had synergistic effects on mass loss.
      Importantly, an increase in F. bidentis litter with a lower C:N ratio in mixtures
      led to greater net release of N over time. These results highlight the importance
      of trait dissimilarity in determining the decomposition rates of litter mixtures
      and suggest that F. bidentis could further synchronize N release from litter as
      an invasion proceeds, potentially creating a positive feedback linked through
      invasion as the invader outcompetes the natives for nutrients. Our findings also
      demonstrate the importance of species composition as well as the identity of
      dominant species when considering how changes in plant community structure
      influence plant invasion.

PMID- 27896464
TI  - A hypergravity environment increases chloroplast size, photosynthesis, and plant
      growth in the moss Physcomitrella patens.
AB  - The physiological and anatomical responses of bryophytes to altered gravity
      conditions will provide crucial information for estimating how plant
      physiological traits have evolved to adapt to significant increases in the
      effects of gravity in land plant history. We quantified changes in plant growth
      and photosynthesis in the model plant of mosses, Physcomitrella patens, grown
      under a hypergravity environment for 25 days or 8 weeks using a custom-built
      centrifuge equipped with a lighting system. This is the first study to examine
      the response of bryophytes to hypergravity conditions. Canopy-based plant growth
      was significantly increased at 10*g, and was strongly affected by increases in
      plant numbers. Rhizoid lengths for individual gametophores were significantly
      increased at 10*g. Chloroplast diameters (major axis) and thicknesses (minor
      axis) in the leaves of P. patens were also increased at 10*g. The area-based
      photosynthesis rate of P. patens was also enhanced at 10*g. Increases in shoot
      numbers and chloroplast sizes may elevate the area-based photosynthesis rate
      under hypergravity conditions. We observed a decrease in leaf cell wall thickness
      under hypergravity conditions, which is in contrast to previous findings obtained
      using angiosperms. Since mosses including P. patens live in dense populations, an
      increase in canopy-based plant numbers may be effective to enhance the toughness
      of the population, and, thus, represents an effective adaptation strategy to a
      hypergravity environment for P. patens.

PMID- 27896467
TI  - Audit of geriatric hip fracture care - a Slovenian trauma center analysis.
AB  - BACKGROUND: The aim was to describe an audit of hip fracture patient care and
      outcomes in a Slovenian healthcare setting prior to the implementation of the
      Geriatric Fracture Center (GFC) model of care. METHODS: The Fragility Fracture
      Network (FFN) hip fracture audit database was used to collect data on hip
      fracture care in elderly patients. Epidemiological data were submitted as well as
      fracture type, prefracture residence and mobility prior to the fracture. The
      timeline of events and acute care data were also collected. Follow-up after 30
      days included hip-related readmission, mobility, residence and life status.
      RESULTS: Included were 495 patients with a mean age of 81 years of which 20% were
      preoperatively seen by a physician or geriatrician, 93.1% had surgical repair,
      58.5% of them within 48 h of admission. The mortality rate in hospital was 5.4%
      and 10.1% at follow-up, 61.8% patients were able to return to prefracture
      residency and 23% could walk with minor assistance. CONCLUSION: This
      comprehensive and detailed audit report provides baseline data on case-mix, care
      and outcomes following hip fractures in Slovenia, in advance of planned quality
      improvement work in geriatric fracture care and provides a strong basis for the
      assessment of the impact of the GFC model of care.

PMID- 27896465
TI  - Psychocardiology in the elderly.
AB  - The population is rapidly aging worldwide and the burden of chronic disease
      follows along. Frequently, diseases go hand in hand and cardiovascular disease
      and mental health problems are no exception. Symptoms of depression in the
      elderly are often overlooked and untreated because they coincide with other
      problems encountered by the elderly. Older adults with depressive symptoms have
      poorer functioning compared to those with chronic medical conditions. The burden
      of cardiovascular disease also remains a leading cause of morbidity and
      mortality. Bidirectional associations between depression and cardiovascular
      diseases are described with a focus on psychosocial factors affecting cardiac
      functioning and disease outcome.

PMID- 27896466
TI  - Early hemodynamic assessment and treatment of elderly patients in the medical
      ICU.
AB  - BACKGROUND AND OBJECTIVES: The aim of this retrospective study was to analyze
      differences in the initial hemodynamic assessment and its impact on the treatment
      in patients aged 80 years or older compared to younger patients during the first
      6 h after admission to the medical intensive care unit (ICU). RESULTS: We
      analyzed 615 consecutive patients admitted to the medical ICU of which 124 (20%)
      were aged 80 years or more. The older group had a significantly higher acute
      physiology and chronic health evaluation (APACHE II) score, an overall mortality
      in the ICU and a presence of pre-existing cardiac disease. Both groups did not
      differ in the presence of shock and shock types on admission. In 57% of older and
      in 56% of younger patients, transthoracic echocardiography was performed with a
      higher therapeutic impact in the older patients. Transesophageal echocardiography
      was performed in 3% of the patients in both groups for specific diagnostic
      problems. Early reassessment with transthoracic echocardiography was necessary in
      5% of the older and in 6% of the younger patients and resulted in a change of the
      treatment in one third of the patients. Continuous invasive hemodynamic
      monitoring was used in 11% of the older and in 10% of the younger patients and
      resulted in a therapeutic change in 71% of the older and in 64% of the younger
      patients. CONCLUSION: Patients aged 80 years or older represent 20% of all
      admissions to the medical ICU. Once admitted the older patients were similarly
      hemodynamically assessed as the younger ones with a similar impact on the
      treatment.

PMID- 27896468
TI  - Evaluation of major trauma in elderly patients - a single trauma center analysis.
AB  - BACKGROUND: The objective of the study was to gather information about elderly
      major trauma patients admitted to one particular Slovenian trauma centre in Celje
      and examine this group of polytrauma patients, specifically with respect to
      mechanisms of injury, injury severity and distribution of injuries. Further on,
      to identify morbidity and mortality rates and compare these to the younger
      population and, finally, to determine the factors that have the most impact on
      treatment results. METHODS: The study gathered and evaluated data of 532 patients
      included in the Trauma Register DGU(r) of the German Trauma Society (TR-DGU)
      during a 10-year period and two distinct groups of patients were established,
      separated on account of age as older or younger than 65 years. The differences
      between these two groups were analyzed with respect to demographics,
      comorbidities, preclinical management, injury patterns, relevant clinical and
      laboratory findings. Furthermore, differences between deceased and surviving
      elderly patients were also analyzed. RESULTS: The majority of elderly patients
      suffered from a blunt mechanism of trauma (96.6%) and of these simple falls
      represented 47.9% within this injury mechanism. There were two body regions,
      which were most frequently represented, namely head and thorax injuries,
      accounting for 54.7% each. Complications were more frequent among the elderly,
      with sepsis being present in 29.9% and multiple organ failure (MOF) in 19.7% of
      cases. Cardiovascular failure was also high in both the elderly and young,
      accounting for 45.3% of the elderly and 31.3% of the younger population. The in
      hospital mortality rate for the elderly group was 25.6% and was significantly
      higher compared to the younger counterparts (14.7%). Low fall mechanism of
      injury, coma and the new injury severity score (NISS) were statistically
      important factors for the mortality of seriously injured elderly patients during
      the acute phase of treatment. CONCLUSIONS: Despite advances in care, morbidity
      and mortality in elderly patients after major trauma remains considerably higher
      than in younger populations with head injuries accounting for the majority of
      fatalities. The elderly patient population in this study mostly suffered from
      blunt mechanisms of injury, with simple falls representing a high proportion of
      injury mechanisms. Generally, the injury severity scale (ISS) in the elderly is
      not statistically higher than with the younger population. Likewise, the
      distribution of injuries according to body regions is also similar; however, the
      elderly are more prone to complications (e. g. sepsis and MOF), which is likely
      due to a lower physiological reserves.

PMID- 27896470
TI  - Erratum to: High rates of clinically relevant incidental findings by total-body
      CT scanning in trauma patients: Results of the REACT-2 trial.

PMID- 27896469
TI  - CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and
      locally advanced pancreatic adenocarcinoma.
AB  - AIM: To assess anatomic changes on computed tomography (CT) after neoadjuvant
      FOLFIRINOX (5-fluorouracil/leucovorin/irinotecan/oxaliplatin) chemotherapy for
      secondary resected borderline resectable (BR) and locally advanced (LA)
      pancreatic adenocarcinoma and their accuracy to predict resectability and
      pathological response. METHODS: Thirty-six patients with secondary resected BR/LA
      pancreatic adenocarcinoma after neoadjuvant FOLFIRINOX chemotherapy (+/-
      chemoradiotherapy) were retrospectively included. Two radiologists reviewed
      baseline and pre-surgical CTs in consensus. NCCN (National Comprehensive Cancer
      Network) classification, largest axis, product of the three axes (P3A), and
      arterial/venous involvement were studied and compared to pathological response
      and resection status and to disease-free survival (DFS). RESULTS: Thirty-one
      patients had R0 resection, including only six exhibiting a downstaging according
      to the NCCN classification. After treatment, the largest axis and P3A decreased
      (P < 0.0001). The pre-surgical largest axis and P3A were smaller in case of R0
      resection (P = 0.019/P = 0.021). The largest axis/P3A variations were higher in
      case of complete pathological response (P = 0.011/P = 0.016). A decrease of the
      arterial/venous involvement was not able to predict R0 or ypT0N0 (P > 0.05).
      Progression of the vascular involvement was seen in two (5 %) patients and led to
      a shorter DFS. CONCLUSION: In BR/LA pancreatic adenocarcinoma after the
      neoadjuvant FOLFIRINOX regimen (+/- chemoradiotherapy), significant tumour size
      decreases were observed on CT. However, CT staging was not predictive of
      resectability and pathological response. KEY POINTS: * Significant tumour size
      decreases were observed on CT after FOLFIRINOX (+/- chemoradiotherapy). * CT is
      not able to predict R0 resection accurately after FOLFIRINOX (+/-
      chemoradiotherapy). * CT is not able to predict complete response accurately
      after FOLFIRINOX (+/- chemoradiotherapy). * Even with a stable NCCN
      classification, BR/LA pancreatic adenocarcinoma could have R0 resection.

PMID- 27896471
TI  - Contrast-enhanced spectral mammography vs. mammography and MRI - clinical
      performance in a multi-reader evaluation.
AB  - OBJECTIVES: To compare the diagnostic performance of contrast-enhanced spectral
      mammography (CESM) to digital mammography (MG) and magnetic resonance imaging
      (MRI) in a prospective two-centre, multi-reader study. METHODS: One hundred
      seventy-eight women (mean age 53 years) with invasive breast cancer and/or DCIS
      were included after ethics board approval. MG, CESM and CESM + MG were evaluated
      by three blinded radiologists based on amended ACR BI-RADS criteria. MRI was
      assessed by another group of three readers. Receiver-operating characteristic
      (ROC) curves were compared. Size measurements for the 70 lesions detected by all
      readers in each modality were correlated with pathology. RESULTS: Reading results
      for 604 lesions were available (273 malignant, 4 high-risk, 327 benign). The area
      under the ROC curve was significantly larger for CESM alone (0.84) and CESM + MG
      (0.83) compared to MG (0.76) (largest advantage in dense breasts) while it was
      not significantly different from MRI (0.85). Pearson correlation coefficients for
      size comparison were 0.61 for MG, 0.69 for CESM, 0.70 for CESM + MG and 0.79 for
      MRI. CONCLUSIONS: This study showed that CESM, alone and in combination with MG,
      is as accurate as MRI but is superior to MG for lesion detection. Patients with
      dense breasts benefitted most from CESM with the smallest additional dose
      compared to MG. KEY POINTS: * CESM has comparable diagnostic performance (ROC
      AUC) to MRI for breast cancer diagnostics. * CESM in combination with MG does not
      improve diagnostic performance. * CESM has lower sensitivity but higher
      specificity than MRI. * Sensitivity differences are more pronounced in dense and
      not significant in non-dense breasts. * CESM and MRI are significantly superior
      to MG, particularly in dense breasts.

PMID- 27896472
TI  - Safety and perioperative morbidity of laparoscopic sacropexy: a systematic
      analysis and a comparison with laparoscopic hysterectomy.
AB  - PURPOSE: The high prevalence of Pelvic Organ Prolapse (POP) along with the
      demographic trend of the ageing population raises the value of sacropexy in the
      treatment of POP. Thus, efforts to decrease risks associated with this procedure
      have the potential for public health impact. We examined the perioperative
      morbidity of laparoscopic sacropexy regarding the surgical access and compared it
      with the morbidity of one of the most common gynecological procedure, the
      laparoscopic hysterectomy. Our aim was to prove the safety of laparoscopic
      sacropexy. METHODS: A retrospective evaluation of 80 consecutive laparoscopic
      sacropexies performed from Sept. 2012 until Oct. 2014 and 126 laparoscopic
      hysterectomies for a benign indication were undertaken. We assessed the
      anatomical outcome and the intra- and postoperative complications using the
      classification system according to Clavien-Dindo (CD). RESULTS: Apical success
      rate after sacropexy was 100% and global success rate was 95% (POP-Q stage <=1).
      The decline in hemoglobin was low in both groups and showed no statistically
      significant differences. Both operative time (P < 0.001) and the duration of
      hospitalization (P < 0.001) were longer in case of a sacropexy. Although overall
      intraoperative complications seemed more frequent during a sacropexy, differences
      were not statistically significant. Both early and late postoperative
      complications showed a higher rate of mild complications (CD-I/II) and a lower
      rate of severe complications (CD-IIIa/IIIb) after a sacropexy. The differences
      were not statistically significant. CONCLUSION: The laparoscopic sacropexy
      represents a safe procedure with good anatomical outcome. Despite higher
      technical severity, it doesn't seem to bare higher risks for perioperative
      morbidity than the laparoscopic hysterectomy does.

PMID- 27896473
TI  - Experience with oral emergency contraception since the OTC switch in Germany.
AB  - PURPOSE: In March 2015, the oral emergency contraceptives levonorgestrel (LNG)
      and ulipristal acetate (UPA) were released from prescription-only status in
      Germany. The main research question is to analyse whether the OTC status of oral
      emergency contraceptives has an influence on the patterns of use. METHODS: All
      information is based on searches for public domain sources on emergency
      contraception. Searches were made for scientific publications, statistics, and
      surveys. RESULTS: Due to additional active ingredient properties, UPA is superior
      to LNG in terms of ovulation-inhibiting effect. Since the OTC switch, demand for
      oral emergency contraceptives has risen by almost 50%, especially at weekends
      when sexual encounters and thus contraceptive failures are most frequent.
      However, the age distribution of the users has not changed as a result of the OTC
      switch. Doctors still play an important role in advising on emergency
      contraception after the removal of the prescription-only requirement. Pregnancies
      despite emergency contraception are terminated in more than half of the cases. In
      federal states with higher rates of use of the morning-after pill, fewer
      terminations of pregnancy were performed. CONCLUSION: As a result of the OTC
      switch, more women and girls use the morning-after pill after unprotected
      intercourse and the time between unprotected intercourse and taking the oral
      emergency contraceptive decreases. This is of great advantage in terms of the
      mechanism of action. UPA is used more frequently than LNG. Only half of all
      people aged between 16 and 39 years in Germany are aware of the morning-after
      pill and 94% of women who had a pregnancy terminated in 2015 did not use any
      emergency contraception after the unprotected intercourse. In the population,
      there is still a great need for information and education on contraception and
      emergency contraception.

PMID- 27896474
TI  - Worldwide prevalence of adverse pregnancy outcomes among singleton pregnancies
      after in vitro fertilization/intracytoplasmic sperm injection: a systematic
      review and meta-analysis.
AB  - PURPOSE: The worldwide prevalence of adverse pregnancy outcomes (APOs) in
      singleton pregnancies after in vitro fertilization (IVF)/intracytoplasmic sperm
      injection (ICSI) is suggested to vary; however, a complete overview is missing.
      The aim of this review is to estimate the worldwide prevalence of APOs associated
      with IVF/ICSI singleton pregnancies. METHODS: PubMed, Google Scholar, Cochrane
      Libraries, and Chinese databases were searched for studies assessing APOs among
      IVF/ICSI singleton births through March 2016. The prevalence estimates were
      summarized and analyzed by meta-analysis. RESULTS: Fifty-two cohort studies, with
      181,741 IVF/ICSI singleton births and 4,636,508 spontaneously conceived singleton
      births, were selected for analysis. Among IVF/ICSI singleton pregnancies, pooled
      estimates were 10.9% [95% confidence interval (CI) 10.0-11.8] for preterm birth,
      2.4% (95% CI 1.9-3.0) for very preterm birth, 8.7% (95% CI 7.4-10.2) for low
      birth weight, 2.0% (95% CI 1.5-2.6) for very low birth weight, 7.1% (95% CI 5.5
      9.2) for small for gestational age, 1.1% (95% CI 0.9-1.3) for perinatal
      mortality, and 5.7% (95% CI 4.7-6.9) for congenital malformations. The IVF/ICSI
      singleton pregnancies have higher prevalence of APOs compared with those
      conceived naturally (all P = 0.000). Significant differences in different
      continents, countries, income groups, and type of assisted conception were found.
      CONCLUSIONS: The IVF/ICSI singleton pregnancies are at a higher prevalence of
      adverse perinatal outcomes compared with those conceived naturally. Important
      geographical differences were found. Yet, population-wide prospective APO
      registries covering the entire world population for IVF/ICSI pregnancies are
      needed to determine the exact perinatal prevalence.

PMID- 27896475
TI  - An exploratory association of polymorphisms in angiogenesis-related genes with
      susceptibility, clinical response and toxicity in gastrointestinal stromal tumors
      receiving sunitinib after imatinib failure.
AB  - The angiogenic pathway plays a pivotal role in tumor growth, invasiveness and
      metastasis. The most important actors in the angiogenic pathway are VEGFA and its
      receptors VEGFR1, 2 and 3. These genes are polymorphic, and the presence of
      single nucleotide polymorphisms may result in angiogenic deregulation. Herein, we
      hypothesized that germline variants may affect sunitinib efficacy (TTP and OS)
      and/or toxicity. Therefore, we investigated 19 polymorphisms, in four genes, in
      54 GIST patients, treated with second-line sunitinib and 147 healthy controls.
      Through a multiple candidate gene approach, we also investigated, for the first
      time, any possible significant associations with GIST susceptibility and clinical
      pathological features. The most important result shows two associations between
      polymorphisms in VEGFR3 rs6877011 (CC vs. CG, OR 9.7, 95% CI 3.31-28.4; P <
      0.001) and rs7709359 (AA+AG vs. GG, OR 5.01, 95% CI 1.33-18.8; P = 0.017) and
      TTP. Interestingly, the association between VEGFR3 rs6877011 and TTP maintained
      the significance after applying the Bonferroni correction for multiple testing (P
      = 0.017). We also highlighted the association with sunitinib-related toxicity; in
      particular, VEGFA polymorphism rs3025039 (CT+TT vs. CC, OR 15.3, 95% CI 2.2
      102.1; P = 0.005) is associated with severe toxicity, with the presence of the
      variant T allele associated with a grade >=3 AE. Because of the small sample size
      and large number of tests performed, we cannot ignore the possibility that some
      associations have been retrieved by chance. However, the influence of VEGF
      polymorphisms in angiogenesis is a hypothesis worthy of exploration in cellular
      models and confirmation in a sizeable cohort of patients.

PMID- 27896476
TI  - Medicinal Chemistry of the Noncanonical Cyclic Nucleotides cCMP and cUMP.
AB  - After decades of intensive research on adenosine-3',5'-cyclic monophosphate
      (cAMP)- and guanosine-3',5'-cyclic monophosphate (cGMP)-related second messenger
      systems, also the noncanonical congeners cyclic cytidine-3',5'-monophosphate
      (cCMP) and cyclic uridine-3',5'-monophosphate (cUMP) gained more and more
      interest. Until the late 1980s, only a small number of cCMP and cUMP analogs with
      sometimes undefined purities had been described. Moreover, most of these
      compounds had been rather synthesized as precursors of antitumor and antiviral
      nucleoside-5'-monophosphates and hence had not been tested for any second
      messenger activity. Along with the recurring interest in cCMP- and cUMP-related
      signaling in the early 2000s, it became evident that well-characterized small
      molecule analogs with reliable purities would serve as highly valuable tools for
      the evaluation of a putative second messenger role of cyclic pyrimidine
      nucleotides. Meanwhile, for this purpose new cCMP and cUMP derivatives have been
      developed, and already known analogs have been resynthesized and highly purified.
      This chapter summarizes early medicinal chemistry work on cCMP and cUMP and
      analogs thereof, followed by a description of recent synthetic developments and
      an outlook on potential future directions.

PMID- 27896477
TI  - How do anthropogenic contaminants (ACs) affect behaviour? Multi-level analysis of
      the effects of copper on boldness in hermit crabs.
AB  - Natural animal populations are increasingly exposed to human impacts on the
      environment, which could have consequences for their behaviour. Among these
      impacts is exposure to anthropogenic contaminants. Any environmental variable
      that influences internal state could impact behaviour across a number of levels:
      at the sample mean, at the level of among-individual differences in behaviour
      ('animal personality') and at the level of within-individual variation in
      behaviour (intra-individual variation, 'IIV'). Here we examined the effect of
      exposure to seawater-borne copper on the startle response behaviour of European
      hermit crabs, Pagurus bernhardus across these levels. Copper exposure rapidly led
      to longer startle responses on average, but did not lead to any change in
      repeatability indicating that individual differences were present and equally
      consistent in the presence and absence of copper. There was no strong evidence
      that copper exposure led to changes in IIV. Our data show that exposure to copper
      for 1 week produces sample mean level changes in the behaviour of hermit crabs.
      However, there is no evidence that this exposure led to changes in repeatability
      through feedback loops.

PMID- 27896478
TI  - Soil microbial communities buffer physiological responses to drought stress in
      three hardwood species.
AB  - Trees possess myriad adaptations for coping with drought stress, but the extent
      to which their drought responses are influenced by interactions with soil
      microbes is poorly understood. To explore the role of microbes in mediating tree
      responses to drought stress, we exposed saplings of three species (Acer
      saccharum, Liriodendron tulipifera, and Quercus alba) to a four week experimental
      drought in mesocosms. Half of the pots were inoculated with a live soil slurry
      (i.e., a microbial inoculum derived from soils beneath the canopies of mature A.
      saccharum, L. tulipifera or Q. alba stands), while the other half of the pots
      received a sterile soil slurry. Soil microbes ameliorated drought stress in L.
      tulipifera by minimizing reductions in leaf water potential and by reducing
      photosynthetic declines. In A. saccharum, soil microbes reduced drought stress by
      lessening declines in leaf water potential, though these changes did not buffer
      the trees from declining photosynthetic rates. In Q. alba, soil microbes had no
      effects on leaf physiological parameters during drought stress. In all species,
      microbes had no significant effects on dynamic C allocation during drought
      stress, suggesting that microbial effects on plant physiology were unrelated to
      source-sink dynamics. Collectively, our results suggest that soil microbes have
      the potential to alter key parameters that are used to diagnose drought
      sensitivity (i.e., isohydry or anisohydry). To the extent that our results
      reflect dynamics occurring in forests, a revised perspective on plant hydraulic
      strategies that considers root-microbe interactions may lead to improved
      predictions of forest vulnerability to drought.

PMID- 27896480
TI  - Ultimate regulation of fecundity in species with precocial young: declining
      marginal value of offspring with increasing brood size does not explain maximal
      clutch size in Black Brent geese.
AB  - Lack 18:125-128 (1967) proposed that clutch size in precocial species was
      regulated by nutrients available to females during breeding. Drent and Daan
      68:225-252 (1980) proposed the individual optimization hypothesis, whereby
      individual state determines the optimal combination of breeding date and clutch
      size. Neither hypothesis accounts for variation in nutrients among females at the
      end of egg laying, strong right truncations in clutch size distributions, or the
      fact that many species with precocial young are determinate layers. One solution
      is that there is a maximum clutch size, above which the number of fledged young
      declines. We manipulated brood size in Black Brent geese to decouple brood size
      from maternal quality and produce broods larger than the natural maximum. We
      recaptured marked goslings to assess variation in prefledging survival as a
      function of brood size and we estimated relative prefledging survival of goslings
      using a Bayesian hierarchical approach. We considered effects of natural clutch
      size, brood size and their interaction on probability that we captured goslings
      at about 4 weeks of age. Prefledging survival declined with increasing brood size
      ([Formula: see text] = -0.53; 95% CI -0.91 to -0.16), while laid clutch size had
      little influence on prefledging survival ([Formula: see text] = -0.04; 95% CI 
      0.42 to 0.32). Despite declining per capita survival with increasing brood size,
      the most productive brood size was six goslings, which is greater than the
      typical maximum clutch size of five. Thus, reduced survival in large broods, by
      itself, is not the sole mechanism that limits maximum clutch size. We suggest
      elsewhere that incubation limitation and lower residual reproductive value for
      females tending larger broods may be other mechanisms limiting maximal clutch
      size in brent.

PMID- 27896479
TI  - Body size drives allochthony in food webs of tropical rivers.
AB  - Food web subsidies from external sources ("allochthony") can support rich
      biological diversity and high secondary and tertiary production in aquatic
      systems, even those with low rates of primary production. However, animals vary
      in their degree of dependence on these subsidies. We examined dietary sources for
      aquatic animals restricted to refugial habitats (waterholes) during the dry
      season in Australia's wet-dry tropics, and show that allochthony is strongly size
      dependent. While small-bodied fishes and invertebrates derived a large proportion
      of their diet from autochthonous sources within the waterhole (phytoplankton,
      periphyton, or macrophytes), larger animals, including predatory fishes and
      crocodiles, demonstrated allochthony from seasonally inundated floodplains,
      coastal zones or the surrounding savanna. Autochthony declined roughly 10% for
      each order of magnitude increase in body size. The largest animals in the food
      web, estuarine crocodiles (Crocodylus porosus), derived ~80% of their diet from
      allochthonous sources. Allochthony enables crocodiles and large predatory fish to
      achieve high biomass, countering empirically derived expectations for negative
      density vs. body size relationships. These results highlight the strong degree of
      connectivity that exists between rivers and their floodplains in systems largely
      unaffected by river regulation or dams and levees, and how large iconic predators
      could be disproportionately affected by these human activities.

PMID- 27896481
TI  - High Perineal and Overall Frequency of Staphylococcus aureus in People Who Inject
      Drugs, Compared to Non-Injectors.
AB  - To investigate the prevalence, distribution, and colonization burden of
      Staphylococcus aureus (S. aureus) and MRSA in different body sites among people
      who inject drugs (PWID) and compare it to a control group consisting of non
      injectors. In this cross-sectional survey, 49 active PWID from the needle
      exchange program (NEP) in Malmo, Sweden, and 60 non-injecting controls from an
      emergency psychiatric inpatient ward at Malmo Addiction Centre were tested for S.
      aureus (including MRSA) by culture, PCR, and MALDI-TOF. Samples were taken from
      anterior nares, throat, perineum, and skin lesions if present. Sixty-seven
      percent of the PWID were colonized with S. aureus, compared to 50% of the
      controls (P = 0.08). Perineal carriage was significantly more frequent among PWID
      than in the control group [37 vs 17%, OR 2.96 (95% CI 1.13-7.75), P = 0.03], also
      after adjusting for sex and age in multivariate analysis [OR 4.01 (95% CI 1.34
      12.03)]. Only one individual in the whole cohort (NEP participant) tested
      positive for MRSA. PWID may be more frequently colonized with S. aureus in the
      perineum than non-injection drug users, and there was a trend indicating more
      frequent overall S. aureus colonization in PWID, as well as higher perineal
      colonization burden. No indication of a high MRSA prevalence among PWID in Sweden
      was noted. However, further MRSA prevalence studies among PWID are needed.
      Knowledge about S. aureus colonization is important for the prevention of S.
      aureus infections with high morbidity in PWID.

PMID- 27896483
TI  - The Effects of Different Carbon Sources on the Antifungal Activity by Lactic Acid
      Bacteria.
AB  - Lactobacillus rhamnosus R-2002 strain isolated from Armenian pickled cheese
      sample has a fungicide effect, which was carried out by the first-time designed
      method. The fungicide effect of LAB strain was expressed after 5 days of co
      cultivation with Mucor plumbeus and 6 days of co-cultivation with Penicillium
      aurantioviolaceum. The growth as well as the antifungal activity of L. rhamnosus
      R-2002 was shown to directly depend on the nature of the medium's carbon source.
      The antifungal activity of this strain against both moulds was inhibited when the
      combination of 10 g l-1 glucose and 10 ml l-1 ethanol in the medium was used as a
      carbon source. The results could be applied in food industry, medicine, and
      veterinary.

PMID- 27896482
TI  - Phage Therapy in Bacterial Infections Treatment: One Hundred Years After the
      Discovery of Bacteriophages.
AB  - The therapeutic use of bacteriophages has seen a renewal of interest blossom in
      the last few years. This reversion is due to increased difficulties in the
      treatment of antibiotic-resistant strains of bacteria. Bacterial resistance to
      antibiotics, a serious problem in contemporary medicine, does not implicate
      resistance to phage lysis mechanisms. Lytic bacteriophages are able to kill
      antibiotic-resistant bacteria at the end of the phage infection cycle. Thus, the
      development of phage therapy is potentially a way to improve the treatment of
      bacterial infections. However, there are antibacterial phage therapy difficulties
      specified by broadening the knowledge of the phage nature and influence on the
      host. It has been shown during experiments that both innate and adaptive immunity
      are involved in the clearance of phages from the body. Immunological reactions
      against phages are related to the route of administration and may vary depending
      on the type of bacterial viruses. For that reason, it is very important to test
      the immunological response of every single phage, particularly if intravenous
      therapy is being considered. The lack of these data in previous years was one of
      the reasons for phage therapy abandonment despite its century-long study.
      Promising results of recent research led us to look forward to a phage therapy
      that can be applied on a larger scale and subsequently put it into practice.

PMID- 27896484
TI  - Oral health status and need for oral care of care-dependent indwelling elderly:
      from admission to death.
AB  - OBJECTIVES: The objective of this study is to assess oral health and oral status
      of elderly patients newly admitted to a nursing home from admission until death.
      MATERIALS AND METHODS: Oral health, oral status, need for dental care,
      cooperation with dental treatment, and given dental care were assessed by two
      geriatric dentists in all new long-stay patients (n = 725) admitted to a nursing
      home between January 2009 and December 2013. All patients were followed from
      admission until death or until they left the nursing home. RESULTS: At admission,
      dementia patients were significantly older than somatic patients; median [IQR]
      ages were, respectively, 85 [79-89] and 81 [76-87] (p = 0.001). In addition,
      edentulous patients were significantly older than patients with remaining teeth,
      83 [79-89] versus 80 [74-86] (p = 0.001) years. Thirty percent of the admitted
      patients died within 12 months after admission. A small minority (20%) of the
      patients had their own teeth. In this group, poor oral hygiene (72%), caries
      (70%), and broken teeth (62%) were frequently observed. Edentulous patients were
      significantly more cooperative with treatment than patients with remaining teeth
      (64 versus 27%). Finally, significantly less professional dental care was given
      to edentulous patients when compared to patients with remaining teeth (median 90
      [IQR 60-180] versus 165 [75-375] min). CONCLUSION: When compared to edentulous
      elderly patients, patients with remaining teeth were younger at admittance, were
      more often non-cooperative, and had a poorer oral health and higher need for
      dental care. CLINICAL RELEVANCE: It is important that health care workers ensure
      adequate oral health and dental care to frail elderly, especially for elderly
      with remaining teeth.

PMID- 27896485
TI  - Biomarkers for precision medicine in bladder cancer.
AB  - Bladder cancer (BC) is classified as non-muscle-invasive BC (NMIBC) or muscle
      invasive BC (MIBC). Because the recurrence and mortality rates of BC are high,
      suitable biomarkers for early detection, evaluation of prognosis, and
      surveillance of drug responses are needed. Urinary markers simplify surveillance
      schedules and improve early detection of tumors, especially in NMIBC. Various
      markers have been identified at DNA, RNA, and protein levels with different
      sensitivities and specificities. Several biomarkers show a higher sensitivity
      than urinary cytology, but they are not accurate enough to replace it. In terms
      of prediction of clinical outcome and treatment response of BC, conventional
      clinical and pathological parameters are widely used, but the predictive ability
      of these parameters is limited; therefore, molecular biomarkers in this field are
      strongly desired. Molecular profiling using fluid and tissue is becoming more
      feasible with recent developments in next-generation sequencing technologies.
      Currently, these profiling methods are beginning to be used for early detection,
      prediction of prognosis, and drug sensitivity. Furthermore, several groups used
      transcriptome profiling to classify MIBC into various distinct subtypes, showing
      distinct clinical behaviors and responses to chemotherapy and immune checkpoint
      inhibitors. The aim of this review is to provide a summary of the most relevant
      biomarkers that have been investigated as diagnostic and prognostic indicators of
      BC.

PMID- 27896488
TI  - Erratum to: Designing 3-Dimensional In Vitro Oviduct Culture Systems to Study
      Mammalian Fertilization and Embryo Production.

PMID- 27896486
TI  - Neural Correlates of the Binaural Masking Level Difference in Human Frequency
      Following Responses.
AB  - The binaural masking level difference (BMLD) is an auditory phenomenon where
      binaural tone-in-noise detection is improved when the phase of either signal or
      noise is inverted in one of the ears (SpiNo or SoNpi, respectively), relative to
      detection when signal and noise are in identical phase at each ear (SoNo).
      Processing related to BMLDs and interaural time differences has been confirmed in
      the auditory brainstem of non-human mammals; in the human auditory brainstem,
      phase-locked neural responses elicited by BMLD stimuli have not been
      systematically examined across signal-to-noise ratio. Behavioral and
      physiological testing was performed in three binaural stimulus conditions: SoNo,
      SpiNo, and SoNpi. BMLDs at 500 Hz were obtained from 14 young, normal-hearing
      adults (ages 21-26). Physiological BMLDs used the frequency-following response
      (FFR), a scalp-recorded auditory evoked potential dependent on sustained phase
      locked neural activity; FFR tone-in-noise detection thresholds were used to
      calculate physiological BMLDs. FFR BMLDs were significantly smaller (poorer) than
      behavioral BMLDs, and FFR BMLDs did not reflect a physiological release from
      masking, on average. Raw FFR amplitude showed substantial reductions in the SpiNo
      condition relative to SoNo and SoNpi conditions, consistent with negative effects
      of phase summation from left and right ear FFRs. FFR amplitude differences
      between stimulus conditions (e.g., SoNo amplitude-SpiNo amplitude) were
      significantly predictive of behavioral SpiNo BMLDs; individuals with larger
      amplitude differences had larger (better) behavioral B MLDs and individuals with
      smaller amplitude differences had smaller (poorer) behavioral B MLDs. These data
      indicate a role for sustained phase-locked neural activity in BMLDs of humans and
      are the first to show predictive relationships between behavioral BMLDs and human
      brainstem responses.

PMID- 27896490
TI  - Cerebrospinal fluid levels of neurofilament light chain in multiple system
      atrophy relative to Parkinson's disease: a meta-analysis.
AB  - As a biomarker of axonal injury, neurofilament light chain (NFL) in multiple
      system atrophy (MSA) patients and Parkinson's disease (PD) patients has been
      investigated by numerous studies. However, cerebrospinal fluid (CSF) NFL changes
      are conflicting in MSA patients relative to PD patients to date. Therefore, the
      current study was carried out to find out possible heterogeneity sources.
      Furthermore, "Neurofilament", "Neurofilament light chain" and "Multiple system
      atrophy" were employed to search "PubMed", "Springer" and "Medline" databases
      until August 2016 with standard mean difference (Std.MD) being calculated. In
      addition, subgroup analysis and meta-regression were performed to assess possible
      heterogeneity sources. Nine studies were pooled, in which 212 MSA patients and
      373 PD patients were involved. Moreover, CSF NFL in MSA patients was higher than
      that in PD patients [pooled Std.MD = 1.56, 95% CI (1.12, 2.00), p < 0.00001] with
      significant heterogeneity (I 2 = 76%). Besides, population variations, sample
      size, the difference in CSF phosphorylated tau (p-tau) levels between MSA
      patients and PD patients, and Hoehn-Yahr staging of PD patients were the main
      heterogeneity sources. As shown by meta-regression, Hedges's g of CSF NFL was
      correlated with CSF Std.MD of alpha-synuclein between MSA patients and healthy
      controls (r = -1.34824, p = 0.00025). Therefore, CSF NFL increased in MSA
      patients relative to PD patients. Meta-regression showed that NFL was associated
      with alpha-synuclein in CSF of MSA patients relative to healthy controls. Due to
      the influence of heterogeneity sources, more prospective large sample studies are
      still needed to assess CSF NFL changes in MSA patients relative to PD patients.

PMID- 27896487
TI  - Natural Compounds as Occult Ototoxins? Ginkgo biloba Flavonoids Moderately Damage
      Lateral Line Hair Cells.
AB  - Several drugs, including aminoglycosides and platinum-based chemotherapy agents,
      are well known for their ototoxic properties. However, FDA-approved drugs are not
      routinely tested for ototoxicity, so their potential to affect hearing often goes
      unrecognized. This issue is further compounded for natural products, where there
      is a lack of FDA oversight and the manufacturer is solely responsible for
      ensuring the safety of their products. Natural products such as herbal
      supplements are easily accessible and commonly used in the practice of
      traditional eastern and alternative medicine. Using the zebrafish lateral line,
      we screened a natural products library to identify potential ototoxins. We found
      that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant,
      demonstrated significant ototoxicity, killing up to 30 % of lateral line hair
      cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar
      levels of ototoxicity. After flavonoid treatment, surviving hair cells
      demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the
      health of the remaining hair cells was compromised. We then asked if these
      flavonoids enter hair cells through the mechanotransduction channel, which is the
      site of entry for many known ototoxins. High extracellular calcium or the
      quinoline derivative E6 berbamine significantly protected hair cells from
      flavonoid damage, implicating the transduction channel as a site of flavonoid
      uptake. Since known ototoxins activate cellular stress responses, we asked if
      reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment
      with the antioxidant D-methionine significantly protected hair cells from each
      flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How
      these products affect mammalian hair cells is still an open question and will be
      the target of future experiments. However, this research demonstrates the
      potential for ototoxic damage caused by unregulated herbal supplements and
      suggests that further supplement characterization is warranted.

PMID- 27896489
TI  - Effects of Iron on Physical and Mechanical Properties, and Osteoblast Cell
      Interaction in beta-Tricalcium Phosphate.
AB  - Iron (Fe) is a vital element and its deficiency causes abnormal bone metabolism.
      We investigated the effects of Fe and its concentration in beta-tricalcium
      phosphate (beta-TCP) on physicomechanical properties and in vitro proliferation
      and differentiation of osteoblasts. Our results showed that Fe addition at
      concentrations of 0.5 wt.% (0.5 Fe-TCP) and 1.0 wt.% (1.0 Fe-TCP) inhibits the
      beta-TCP to alpha-TCP phase transformation at sintering temperature of 1250 
      degrees C. Addition of 0.25 wt.% Fe (0.25 Fe-TCP) increased the compressive
      strength of beta-TCP from 167.27 +/- 16.2 to 227.10 +/- 19.3 MPa. After 3 days of
      culture, surfaces of 0.5 Fe-TCP and 1.0 Fe-TCP samples were covered by osteoblast
      cells, compared to that of pure and 0.25 Fe-TCP. Cells grew to confluency on all
      Fe-doped samples after 7 days of culture and monolayer sheet-like cellular
      structure was found at 11 days. Optical cell density and alkaline phosphatase
      activity were significantly higher on Fe-doped samples and the highest values
      were found in 0.5 Fe-TCP samples. Our results show that Fe concentration had
      significant effect on physical and mechanical properties of TCP ceramics, and
      also on the in vitro osteoblast cellular interactions in TCP ceramics.

PMID- 27896492
TI  - Hemianopic line bisection error in a patient with Alzheimer's disease.
AB  - Visual symptoms are frequently observed in posterior cortical atrophy compared to
      typical amnestic Alzheimer's disease (AD). We report the case of a patient with
      amnestic AD with long-lasting homonymous hemianopia. A 62-year-old woman, who was
      diagnosed in amnestic AD, complained of visual disturbance. She had left
      homonymous hemianopia in the perimetry test and left tactile extinction.
      Regardless of posture, retinotopically leftward error was observed on 21 cm line
      bisection test. Brain single photon emission computerized tomography (SPECT)
      showed bilateral temporoparietal hypoperfusion, which was more severe to the
      right than left side. This case suggested that long-lasting hemianopia could
      occur in the patient with amnestic AD and that hemianopic line bisection error
      might be compensatory mechanism.

PMID- 27896491
TI  - Clusters of cognitive impairment among different phenotypes of myotonic dystrophy
      type 1 and type 2.
AB  - Neuropsychological examinations in myotonic dystrophy (DM) patients show a great
      variability of results from a condition of intellectual disability to the subtle
      cognitive impairments. It is unclear if different clusters of neuropsychological
      deficits appear in different phenotypes of DM, or if there are patients with no
      cognitive deficit at all. The aim of this study is to assess cognitive
      impairments among patients with different phenotypes of DM type 1 (DM1) and type
      2 (DM2), and to potentially define cognitive clusters in these disorders. Study
      comprised 101 DM1 and 46 DM2 adult patients who were genetically confirmed.
      Patients underwent analysis of five cognitive domains (visuospatial, executive,
      attention, memory and language). Virtually all DM1 patients had cognitive defect
      with approximately 2-3 cognitive domains affected. On the other hand, one-third
      of DM2 patients had completely normal neuropsychological findings, and in other
      two-thirds approximately 1-2 domains were affected. Cluster analysis showed that
      in both diseases visuospatial and executive dysfunctions seemed to be the main
      cognitive defects, while memory and language impairments appeared in more severe
      phenotypes. Our results showed that a single form of DM1 or DM2 may consist of
      several cognitive clusters. Understanding of cognitive impairments in DM is very
      important to follow positive and side effects in ongoing and future clinical
      trials.

PMID- 27896493
TI  - Hearing impairment and risk of Alzheimer's disease: a meta-analysis of
      prospective cohort studies.
AB  - Observational studies suggested an association between hearing impairment and
      cognitive disorders. However, whether hearing impairment is an independent risk
      factor or a harbinger of Alzheimer's disease remains controversial. Our goal was
      to assess the association between hearing impairment (HI) and the risk of
      Alzheimer's disease (AD) by conducting a meta-analysis of prospective cohort
      studies. We comprehensively searched the PubMed, Embase, Web of Science and
      Cochrane Library databases on January 19, 2016 to incorporate all the prospective
      cohort studies meeting the inclusion criteria to perform a systematic review and
      meta-analysis. Four prospective cohort studies with comparison between hearing
      impairment and normal hearing were incorporated, with 7461 participants. The
      outcomes of three studies were the incidence of Alzheimer's disease and the
      outcome of the fourth study was the incidence of mild cognitive impairment. The
      overall combined relative risk of people with hearing impairment to develop
      Alzheimer's disease was 4.87 (95% CI 0.90-26.35; p = 0.066), compared with the
      control group. Since both Alzheimer's disease and mild cognitive impairment are
      cognitive disorders, we incorporated all the four studies and the overall
      combined relative risk was 2.82 (95% CI 1.47-5.42; p = 0.002), indicating that
      the difference was significant. This meta-analysis suggests that hearing
      impairment significantly increases the risk of cognitive disorders and future
      well-designed prospective cohort studies are awaited to confirm the association
      between hearing impairment and risk of Alzheimer's disease.

PMID- 27896494
TI  - Endohedral metalloborofullerenes M@B44 (M = Ca, Sr, Ba): a computational
      investigation.
AB  - For the first time, the structures, stabilities and electronic properties of
      alkaline-earth metal doped B44 fullerenes were investigated by means of density
      functional theory calculations. Our results reveal that M@B44 (M = Ca, Sr, Ba)
      possess endohedral configurations as their lowest energy structures, whereas the
      exohedral form is favored when metal is Be or Mg. The large binding energies and
      sizable HOMO-LUMO gap energies of Ca@B44, Sr@B44 and Ba@B44 suggest the
      considerable possibility to achieve these novel endohedral borofullerenes
      experimentally. Born-Oppenheimer molecular dynamics (BO-MD) simulations at
      various temperatures further confirmed the extreme dynamic stabilities of these
      endohedral complexes. Their bonding patterns were also analyzed in detail.
      Finally, we simulated their infrared absorption spectra and 11B nuclear magnetic
      resonance spectra to help future structural characterization. Graphical Abstract
      Stuffing B44 fullerene with metals.

PMID- 27896496
TI  - Dalbavancin reduces biofilms of methicillin-resistant Staphylococcus aureus
      (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE).
AB  - Activity of dalbavancin against methicillin-resistant Staphylococcus aureus
      (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) in biofilm was
      investigated and the microbicidal biofilm concentrations (MBC) were determined.
      Biofilms obtained from ten MRSA and ten MRSE bloodstream isolates, collected from
      patients in the General Hospital of Vienna between 2012 and 2015, were incubated
      with dalbavancin in trypticase soy broth (TSB) in serial dilution from 0.0625
      mg/l to 256 mg/l using a microtiter plate biofilm model. The plates were
      incubated for 24 h at 37  degrees  C and 50% humidity. Biofilms were fixed with
      2.5% glutaraldehyde and stained with crystal violet. Subsequently the optical
      density (OD620) was used to measure the MBC, defined as the concentration of
      dalbavancin leading to a 50% reduction of biofilm. MBC for MRSA was 1 mg/l-4 mg/l
      (minimal inhibitory concentrations (MIC) 0.0312 mg/l-0.064 mg/l). MBC for MRSE
      was 2 mg/l-16 mg/l (MIC 0.023 mg/l-0.0625 mg/l). Dalbavancin successfully reduced
      MRSA and MRSE in biofilms, and therefore provides a promising option for the
      treatment of biofilm-associated infections.

PMID- 27896497
TI  - The slippery difficulty of ever containing drug resistance with current
      practices.
AB  - It has previously been shown that the rate of drug resistance emergence in
      medicine is exponential, while we have been producing drugs at a much lower rate.
      Our ability to successfully contain resistance at any one time is function of how
      many drugs we have at our disposal to counter new resistances from pathogens.
      Here, we assess our level of preparedness through a mathematical comparison of
      the drug manufacture rate by the pharmaceutical industry with the resistance
      emergence rate in pathogens. To that effect, changes in the rates of growth of
      the drugs production and resistance emergence processes are computed over
      multiple time segments and compared. It is found that new resistance emergence
      rate in infectious diseases medicine remains mathematically and permanently ahead
      of the drugs production rate by the pharmaceutical industry. Consequently, we are
      not in a position to ever contain current or future strengths of resistance from
      pathogens. A review of current practices is called for.

PMID- 27896495
TI  - Accuracy of coronary computed tomography angiography for bioresorbable scaffold
      luminal investigation: a comparison with optical coherence tomography.
AB  - To establish the accuracy of coronary computed tomography angiography (CTA) for
      in-scaffold quantitative evaluation with optical coherence tomography (OCT) as a
      reference. The translucent backbone of the bioresorbable scaffold allow us to
      evaluate non-invasively the coronary lumen with coronary CTA. In the ABSORB first
      in-man studies, coronary CTA was shown to be feasible for quantitative luminal
      assessment. Nevertheless, a comparison with an intravascular modality with higher
      resolution has never been performed. In the ABSORB Cohort B trial, 101 patient
      with non-complex lesions were treated with the fully biodegradable vascular
      scaffold. For this analysis, all patients who underwent coronary CTA at 18 months
      and OCT within +/-180 days were included. Coronary CTA and OCT data were analysed
      at an independent core laboratory for quantitative cross-sectional luminal
      dimensions. The primary objective was the accuracy and precision of coronary CTA
      for in-scaffold minimal lumen area assessment, with OCT as a reference. Among the
      101 patients of the ABSORB Cohort B trial, 35 underwent both OCT and coronary
      CTA. The feasibility of quantitative evaluation was 74%. In the scaffolded
      segment, coronary CTA underestimated minimal lumen area by 9.8% (accuracy 0.39
      mm2, precision 1.0 mm2, 95% limits of agreement -1.71 to 2.50 mm2). A similar
      level of agreement was observed in the non-scaffolded segment. Compared to OCT,
      coronary CTA appears to be accurate for the estimation of in-scaffold luminal
      areas, with no difference compared to the non-scaffolded region.

PMID- 27896498
TI  - Ratchet effect for two-dimensional nanoparticle motion in a corrugated
      oscillating channel.
AB  - The motion of a single rigid or elastic particle inside a corrugated narrow
      channel is investigated by means of Brownian dynamics simulations. Periodic
      oscillations of one of the asymmetric channel surfaces induce directed particle
      transport. For different surface structures of the resting channel surface, we
      determine optimal transport properties in terms of the driving frequency,
      particle size, and corrugation amplitude. The transport direction is changed when
      switching from perpendicular motion of the oscillating surface to parallel motion
      with respect to the resting surface, which can be rationalized by a transition
      from a flashing to a pushing ratchet effect. We also study the diffusion behavior
      and find strongly enhanced diffusion for parallel oscillatory motion with a
      diffusivity significantly larger than for free diffusion. Elastic large particles
      exhibit suppressed transport with increasing rigidity. In contrast, for small
      particles, increasing rigidity enhances the particle transport both in terms of
      particle velocity and diffusivity.

PMID- 27896499
TI  - Phase behaviour of colloids plus weakly adhesive polymers.
AB  - The phase behaviour of a colloidal dispersion mediated by weakly adhesive
      polymers is considered. The polymers are depleted but are weakly adhesive and
      hence comprise a non-zero polymer concentration at the colloid's surface, in
      contrast to the classical assumption in depletion theories involving a zero
      polymer concentration at the surface. The theory is composed of a generalized
      free-volume theory for colloid-polymer mixtures and a self-consistent mean-field
      theory for polymers at surfaces. It is found that the weak adhesion of the
      polymers shifts the phase stability of the colloid-polymer mixtures to higher
      polymer concentrations as compared to assuming a full depletion effect. The
      predicted phase diagrams employing the new theory are consistent with experiments
      on mixtures of silica spheres coated with stearyl alcohol and
      polydimethylsiloxane in cyclohexane and with Monte Carlo simulation results.

PMID- 27896500
TI  - Differences in the adsorption of nafamostat mesilate between polyester-polymer
      alloy and polysulfone membranes.
AB  - We previously experienced severe clot formation in a polyester-polymer alloy
      (PEPA) dialyzer and hemodialysis (HD) circuit with nafamostat mesilate (NM) as an
      anticoagulant. The possibility of NM adsorption to the PEPA membrane was taken
      into consideration, but there was not enough information. In the present study,
      we evaluated differences in the adsorption of NM between a PEPA membrane (FDX-120
      GW, Nikkiso, Tokyo, Japan) and two different polysulfone membranes (FX-140,
      Fresenius Medical Care, Tokyo, Japan; NV-15U, Toray Medical, Tokyo, Japan). We
      calculated the NM concentration by measuring absorbance at 241 nm using a
      spectrometer. NM adsorption was evaluated in three ways. First, we evaluated NM
      adsorption to hollow fibers. Then, we passed an NM solution through dialyzers and
      evaluated its adsorption in a single-pass examination. Finally, we circulated an
      NM solution in an HD circuit using a blood pump and evaluated NM adsorption. In
      all the experiments, NM adsorption to the PEPA membrane was greater than that to
      the polysulfone membranes examined. In the blood pump experiment, the estimated
      adsorption quantities of NM to the PEPA membrane and the FX-140 and NV-15U
      polysulfone membranes were 12.0 +/- 0.1, 1.0 +/- 0.1, and 4.1 +/- 0.4 mg/m2,
      respectively. NM adsorption was confirmed, especially in the early phase, and the
      PEPA membrane adsorbed greater amounts of NM than the polysulfone membranes. We
      should pay attention to the choice of dialyzer as well as the appropriate dose of
      NM administration during the preparation of HD circuits.

PMID- 27896501
TI  - A manganese catalase from Thermomicrobium roseum with peroxidase and catecholase
      activity.
AB  - An enzyme with catechol oxidase activity was identified in Thermomicrobium roseum
      extracts via solution assays and activity-stained SDS-PAGE. Yet, the genome of T.
      roseum does not harbor a catecholase gene. The enzyme was purified with two anion
      exchange chromatography steps and ultimately identified to be a manganese
      catalase with additional peroxidase and catecholase activity. Catalase activity
      (6280 +/- 430 IU/mg) clearly dominated over pyrogallol peroxidase (231 +/- 53
      IU/mg) and catecholase (3.07 +/- 0.56 IU/mg) activity as determined at 70 
      degrees C. Most enzyme kinetic properties were comparable to previously
      characterized manganese catalase enzymes. Catalase activity was highest at
      alkaline pH values and showed inhibition by excess substrate and chloride. The
      apparent K m and k cat values were 20 mM and 2.02 * 104 s-1 subunit-1 at 25 
      degrees C and pH 7.0.

PMID- 27896502
TI  - Supporting of the Fathers to Visit Their Infants in Neonatal Intensive Care Unit
      Decreases Their Stress Level: A Pretest-Posttest Quasi-Experimental Study.
AB  - It is known that fathers whose infants are hospitalized in NICUs (Neonatal
      Intensive Care Units) are severely stressed. This study was conducted for the
      purpose of determining the effect of supporting and visiting infants in NICUs on
      stress levels of Turkish fathers. This was a pretest-posttest quasi-experimental
      study. The population of the study consisted of 47 fathers who had their infants
      receiving treatment in NICU at a state hospital in the eastern Turkey and agreed
      to participate in the study. The data were collected by using "Father-Infant
      Introductory Information Form" and "Parental Stressor Scale: Neonatal Intensive
      Care Unit, PSS:NICU". When comparing the PSS:NICU total mean scores of the
      fathers before and after interventions; it was determined that their mean scores
      were higher before visits compared to those obtained after interventions and the
      difference between them was significant at advanced level. It was found that the
      fathers visiting and supporting their infants in NICUs had the decreased stress
      levels. It is a useful nursing intervention to support fathers to visit their
      babies in NICUs and establish environments where they could spend time with their
      babies.

PMID- 27896503
TI  - Effect of PGC-1alpha overexpression or silencing on mitochondrial apoptosis of
      goat luteinized granulosa cells.
AB  - During goat follicular development, abnormal expression of peroxisome
      proliferator- activated receptor gamma coactivator-1 alpha (PGC-1alpha) in
      granulosa cells (GCs) may contribute to follicular atresia with unknown
      regulatory mechanisms. In this study, we investigate the effect of ectopic
      expression or interference of PGC-1alpha on cell apoptosis of goat first passage
      granulosa cells (FGCs) in vitro. The results indicate that PGC-1alpha silencing
      by short hairpin RNA (shRNA) in goat FGCs significantly reduced mitochondrial DNA
      (mtDNA) copy number (P < 0.05), changed mitochondria ultrastructure, and induced
      cell apoptosis (P < 0.05). The transcription and translation levels of the
      apoptosis-related genes BCL-2-associated X protein (BAX), caspase 3, and caspase
      9 were significantly up-regulated (P < 0.05, respectively). Moreover, the ratio
      of BAX/B-cell lymphoma 2 (BCL-2) was reduced (P < 0.05), and the release of
      cytochrome c (cyt c) and lactate dehydrogenase (LDH) was significantly enhanced
      (P < 0.05, respectively) in PGC-1alpha interference goat FGCs. Furthermore, the
      expression of anti-oxidative related genes superoxide dismutase 2 (SOD2),
      glutathione peroxidase (GPx) and catalase (CAT) was down-regulated (P < 0.05,
      respectively) and the activity of glutathione/glutathione disulfide (GSH/GSSG)
      was inhibited (P < 0.05). While enforced expression of PGC-1alpha increased the
      levels of genes involved in the regulation of mitochondrial function and
      biogenesis, and enhanced the anti-oxidative and anti-apoptosis capacity. Taken
      together, our results reveal that lack of PGC-1alpha may lead to mitochondrial
      dysfunction and disrupt the cellular redox balance, thus resulting in goat GCs
      apoptosis through the mitochondria-dependent apoptotic pathway.

PMID- 27896505
TI  - Focused Versus Bilateral Parathyroid Exploration for Primary Hyperparathyroidism:
      A Systematic Review and Meta-analysis.
AB  - BACKGROUND: Focused exploration (FE) and bilateral parathyroid exploration (BE)
      are the standard surgical options for patients with primary hyperparathyroidism.
      However, the relative risk of recurrence, persistence, overall failure,
      reoperation, and any complications associated with either surgical approach is
      unclear. This study compared the outcomes and complication rates after FE and BE
      for patients with primary hyperparathyroidism. METHODS: PubMed and Embase were
      searched for studies comparing these outcomes between FE and BE. A meta-analysis
      was performed using RevMan 5.3 software. Published data were pooled using the
      DerSimonian random-effect model, and results were presented as odds ratio (OR) or
      mean difference with 95% confidence interval (CI). RESULTS: A total of 12,743
      patients from 19 studies were included in this meta-analysis. In comparison with
      BE, the FE arm had comparable rates of recurrence (OR 1.08; 95% CI 0.59-2.00; p =
      0.80; n = 9 studies), persistence (OR 0.89; 95% CI 0.58-1.35; p = 0.58; n = 13),
      overall failure (OR 0.88; 95% CI 0.58-1.34; p = 0.56; n = 13), and reoperation
      (OR 1.05; 95% CI 0.25-4.32; p = 0.95, n = 4). The operative time was
      significantly shorter (mean difference = -39.86; 95% CI -53.05 to -26.84; p <
      0.01, n = 9), with a lower overall complication rate in the FE arm (OR  0.35; 95%
      CI 0.15-0.84; p = 0.02; n = 12). The latter was attributed predominantly to a
      lower risk of transient hypocalcemia (OR  0.36; 95% CI 0.14-0.90; p = 0.03; n =
      9). There was a significant heterogeneity among these studies for all outcomes
      except for disease recurrence. CONCLUSIONS: Compared with BE, FE has similar
      recurrence, persistence, and reoperation rates but significantly lower overall
      complication rates and shorter operative time.

PMID- 27896504
TI  - Essential Resources for Implementation and Sustainability of Evidence-Based
      Health Promotion Programs: A Mixed Methods Multi-Site Case Study.
AB  - As of October 2016, use of federal Older Americans Act funds for health promotion
      and disease prevention will be restricted to the Administration on Aging's
      criteria for high-level evidence-based health promotion programs. Dissemination
      of these programs to rural communities remains limited. Therefore a strong need
      exists to identify strategies that facilitate program implementation and
      sustainability. The objective of this study was to compare organizational
      readiness and implementation strategies used by rural communities that achieved
      varying levels of success in sustaining evidence-based health promotion programs
      for older adults. We utilized a qualitative multi-site case study design to
      analyze the longitudinal experiences of eight rural sites working to implement
      evidence-based health promotion program over 3 years (8/2012-7/2015). Multiple
      sources of data (interviews, documents, reports, surveys) from each site informed
      the analysis. We used conventional content analysis to conduct a cross-case
      comparison to identify common features of rural counties that successfully
      implemented and sustained their target evidence-based health promotion program.
      Readiness to implement evidence-based programs as low at baseline as all site
      leaders described needing to secure additional resources for program
      implementation. Sites that successfully utilized six essential resources
      implemented and sustained greater numbers of workshops: (1) External
      Partnerships, (2) Agency Leadership Commitment, (3) Ongoing Source of Workshop
      Leaders, (4) Health Promotion Coordination Tasks Assigned to Specific Staff, (5)
      Organizational Stability, and (6) Change Team Engagement. The six essential
      resources described in this study can help rural communities assess their
      readiness to implement health promotion programs and work secure the resources
      necessary for successful implementation.

PMID- 27896506
TI  - Inflammation-Based Prognostic Scores: Utility in Prognostication and Patient
      Selection for Cytoreduction and Perioperative Intraperitoneal Chemotherapy in
      Patients with Peritoneal Metastasis of Colonic Origin.
AB  - BACKGROUND: Tumor-associated systemic inflammatory response has been correlated
      with prognosis. Our aim was to analyze the utility of inflammation-based
      prognostic scores for prognostication and patient selection for cytoreduction and
      perioperative intraperitoneal chemotherapy (POIC) in patients diagnosed with
      peritoneal metastasis of colonic origin. METHODS: A retrospective analysis of a
      prospectively maintained database for all patients treated for peritoneal
      metastasis of colonic origin from February 2001 to April 2015. Inflammation-based
      prognostic scores including neutrophil-lymphocyte ratio, platelet-lymphocyte
      ratio (PLR) and Onodera's prognostic nutritional index (ONI) were calculated.
      RESULTS: Of 123 patients, 70 (56.9%) were men and 53 (43.1%) were women. Mean age
      at diagnosis was 49.9 years. Significant prognosticators in univariate analysis
      included intraoperative peritoneal cancer index (p < 0.000), tumor marker CA19-9
      (p < 0.000), PLR (p = 0.020), POIC regimen (p < 0.003), and completeness of
      cytoreduction (p < 0.000). Multivariate Cox analysis identified CA19-9 (hazard
      ratio [HR] 1.0; 95% confidence interval [CI] 1.00-1.01, p = 0.031), ONI (HR 0.86;
      95% CI 0.79-0.94, p < 0.000), PLR (HR 1.0; 95% CI 0.90-1.01, p = 0.041),
      incompleteness of cytoreduction CC2 and CC3, and mucinous adenocarcinoma
      histology as significant independent prognosticators. CONCLUSIONS: The
      inflammation-based prognostic scores PLR and ONI and tumor marker CA19-9 are
      significant prognosticators of survival. They are useful in patient selection and
      prognostication for cytoreductive surgery and POIC in patients with peritoneal
      carcinomatosis of colonic origin.

PMID- 27896507
TI  - Levonorgestrel-Releasing Intrauterine Systems Versus Oral Cyclic
      Medroxyprogesterone Acetate in Endometrial Hyperplasia Therapy: A Meta-Analysis.
AB  - BACKGROUND: This study aimed to compare the levonorgestrel-releasing intrauterine
      system (LNG-IUS) with oral cyclic medroxyprogesterone acetate (MPA) in
      endometrial hyperplasia therapy using randomized controlled trials (RCTs).
      METHODS: The study searched MEDLINE, EMBASE, CENTRAL, and other databases. All
      regression outcomes were calculated for dichotomous outcomes in terms of relative
      risk (RR) and 95% confidence intervals (CIs) using a Mantel-Haenszel random
      effects model. RESULTS: The search found 543 articles but selected 342 articles
      after the removal of duplicates. A meta-analysis found five RCTs (377 patients).
      The study did not analyze RR for total outcome because of high heterogeneity (I 2
      = 87%). In a subgroup analysis of studies with non-obese women, the LNG-IUS
      treatment appeared to have a higher regression rate than oral MPA (RR 1.41; 95%
      CI 1.23-1.62; 4 trials, 265 patients; I 2 = 0%). In a subgroup analysis of
      studies with obese women, LNG-IUS appeared to have a regression rate similar to
      that of oral MPA (RR 1.03; 95% CI 0.94-1.13; 1 trial, 60 patients). In a subgroup
      analysis according to histology in the non-obese group, the LNG-IUS treatment
      appeared to have a higher regression rate than oral cyclic MPA in a meta-analysis
      of women with non-atypical endometrial hyperplasia (RR 1.36; 95% CI 1.07-1.73; 2
      trials, 92 patients; I 2 = 6%) and mixed endometrial hyperplasia (atypical and
      non-atypical) (RR 1.44; 95% CI 1.21-1.71; 2 trials, 173 patients; I 2 = 0%).
      CONCLUSIONS: The LNG-IUS treatment has a higher regression rate than cyclic MPA
      in non-atypical endometrial hyperplasia and mixed endometrial hyperplasia therapy
      for non-obese women but has a similar regression rate, albeit limited, for obese
      women.

PMID- 27896508
TI  - Trends in Mortality After Primary Cytoreductive Surgery for Ovarian Cancer: A
      Systematic Review and Metaregression of Randomized Clinical Trials and
      Observational Studies.
AB  - BACKGROUND: Primary cytoreductive surgery (PDS) followed by platinum-based
      chemotherapy is the cornerstone of treatment and the absence of residual tumor
      after PDS is universally considered the most important prognostic factor. The aim
      of the present analysis was to evaluate trend and predictors of 30-day mortality
      in patients undergoing primary cytoreduction for ovarian cancer. METHODS:
      Literature was searched for records reporting 30-day mortality after PDS. All
      cohorts were rated for quality. Simple and multiple Poisson regression models
      were used to quantify the association between 30-day mortality and the following:
      overall or severe complications, proportion of patients with stage IV disease,
      median age, year of publication, and weighted surgical complexity index. Using
      the multiple regression model, we calculated the risk of perioperative mortality
      at different levels for statistically significant covariates of interest.
      RESULTS: Simple regression identified median age and proportion of patients with
      stage IV disease as statistically significant predictors of 30-day mortality.
      When included in the multiple Poisson regression model, both remained
      statistically significant, with an incidence rate ratio of 1.087 for median age
      and 1.017 for stage IV disease. Disease stage was a strong predictor, with the
      risk estimated to increase from 2.8% (95% confidence interval 2.02-3.66) for
      stage III to 16.1% (95% confidence interval 6.18-25.93) for stage IV, for a
      cohort with a median age of 65 years. CONCLUSIONS: Metaregression demonstrated
      that increased age and advanced clinical stage were independently associated with
      an increased risk of mortality, and the combined effects of both factors greatly
      increased the risk.

PMID- 27896510
TI  - Standard Clinical Protocol for Bidirectional Hyperthermic Intraperitoneal
      Chemotherapy (HIPEC): Systemic Leucovorin, 5-Fluorouracil, and Heated
      Intraperitoneal Oxaliplatin in a Chloride-Containing Carrier Solution.
AB  - BACKGROUND: Intraperitoneal chemotherapy has an established role in the treatment
      of selected patients with colorectal peritoneal metastases. Oxaliplatin is highly
      suitable as a chemotherapeutic agent for hyperthermic intraperitoneal
      chemotherapy (HIPEC), but its use to date has been limited because of the
      morbidity caused by severe electrolyte and glycemic imbalances associated with 5%
      glucose as its carrier solution. This report provides an overview of the
      development, rationale, and application of intraperitoneal chemotherapy and the
      use of various drugs and carrier solutions. A novel, evidence-based protocol for
      bidirectional oxaliplatin-based HIPEC in a physiologic carrier solution (Dianeal
      PD4 dextrose 1.36%) is presented, and its impact on electrolyte and glucose
      levels is demonstrated. METHODS: After implementation of the new protocol, the
      serum electrolyte (sodium, potassium, and chloride) levels, glucose levels, and
      intravenous insulin requirements were intensively measured in eight consecutive
      cases immediately before HIPEC (T = 0), immediately after HIPEC (T = 30), 1 h
      after HIPEC (T = 60), and 3 h after HIPEC (T = 180). RESULTS: The median sodium
      levels were 140 mmol/L at T = 0, 138 mmol/L at T = 30, 140 mmol/L at T = 60, and
      140 mmol/L at T = 180. The respective median potassium levels were 4.6, 4.2, 3.7,
      and 3.9 mmol/L, and the respective median chloride levels were 112, 111, 111, and
      112 mmol/L. The respective median glucose levels were 9, 11.5, 10.7, and 8.6
      mmol/L. The median insulin requirements were respectively 0.5, 1.5, 1.2, and 0
      U/h. None of the patients were diabetic. CONCLUSION: Using a novel protocol for
      bidirectional oxaliplatin-based HIPEC in Dianeal instead of 5% glucose, the
      observed fluctuations in this study were minimal and not clinically relevant
      compared with historical values for electrolyte and glycemic changes using 5%
      glucose as a HIPEC carrier solution. This novel protocol leads to only minimal
      and clinically irrelevant electrolyte and glycemic disturbances, and its adoption
      as the standard protocol for oxaliplatin-based HIPEC should be considered.

PMID- 27896509
TI  - Shape and Enhancement Characteristics of Pancreatic Neuroendocrine Tumor on
      Preoperative Contrast-enhanced Computed Tomography May be Prognostic Indicators.
AB  - BACKGROUND: Prognostic indicators of the malignant potential of pancreatic
      neuroendocrine tumors (PNET) are limited. We assessed tumor shape and enhancement
      pattern on contrast-enhanced computed tomography as predictors of malignant
      potential. METHODS: Sixty cases of PNET patients undergoing curative surgery from
      2001 to 2014 were enrolled onto our retrospective study. Preoperative enhanced
      CTs were assessed, and criteria defined for regularly shaped and enhancing tumors
      (group 1), and irregularly shaped and/or enhancing tumors (group 2). The relation
      of tumor shape and enhancement pattern to outcome was assessed. RESULTS:
      Interobserver agreement was substantial (kappa = 0.74). Group 2 (n = 24) was
      significantly correlated with synchronous liver metastasis (23 vs. 0 %), lymph
      node metastasis (36 vs. 3 %), pathologic capsular invasion (68 vs. 8 %), larger
      tumor size (30 vs. 12 mm), tumor, node, metastasis classification system (TNM)
      stage III/IV disease (46 vs. 3 %), and histologic grade 2/3 (41 vs. 0 %).
      Multivariate analysis revealed that tumor grade 2/3 and group 2 criteria
      correlated with tumor relapse (hazard ratio 6.5 and 13.6, P = 0.0071 and 0.039,
      respectively), and that only group 2 criteria were independently correlated with
      poor overall survival (hazard ratio 5.56e + 9, P = 0.0041). CONCLUSIONS:
      Irregular tumor shape/enhancement on preoperative computed tomography is a
      negative prognostic factor after curative surgery for PNET.

PMID- 27896511
TI  - Resection of Pheochromocytoma Improves Diabetes Mellitus in the Majority of
      Patients.
AB  - BACKGROUND: Catecholamine excess in patients with pheochromocytoma often results
      in impaired glucose tolerance, leading to diabetes mellitus. Little data are
      available on the long-term effect of surgery on diabetes. OBJECTIVE: The primary
      aim of this study was to determine the likelihood of diabetes cure after surgery,
      while secondary objectives were to determine risk factors for development of
      diabetes preoperatively and persistence of diabetes postoperatively. METHODS: All
      patients undergoing surgery for pheochromocytoma from 1996 to 2015 were
      retrospectively reviewed to identify those with a preoperative diagnosis of
      diabetes. Demographic and diabetes-specific data were collected. Median follow-up
      was 52.1 months. RESULTS: Overall, 153 patients underwent surgery. Diabetes was
      seen in 36 (23.4%) patients. Eight patients met the exclusion criteria and were
      removed from the final analysis, while 22 (78.6%) patients had complete
      resolution of diabetes. Four patients remained on medication with improved
      control. Overall, 93.0% of patients had improvement of their diabetes; two
      patients did not improve. Patients with large, symptomatic tumors were more
      likely to develop preoperative diabetes, and diabetes was more likely to persist
      in patients who had an elevated body mass index (BMI). CONCLUSIONS: Diabetes was
      found concurrently with pheochromocytoma in 23% of patients, more often in those
      with large, symptomatic tumors. The majority of patients had long-term resolution
      of diabetes after successful resection; however, some patients may continue to
      require treatment of diabetes after operation, especially those with a higher
      BMI.

PMID- 27896512
TI  - Cytoreduction (Peritonectomy Procedures) Combined with Hyperthermic
      Intraperitoneal Chemotherapy (HIPEC) in Advanced Ovarian Cancer: Retrospective
      Italian Multicenter Observational Study of 511 Cases.
AB  - PURPOSE: The aim of this study was to help with the process of selecting patients
      with advanced ovarian cancer to undergo cytoreductive surgery (CRS) with
      hyperthermic intraperitoneal chemotherapy (HIPEC) by analyzing outcome data at
      distinct clinical time points reflecting the natural history of the disease.
      METHODS: In a retrospective Italian multicenter study investigating patients with
      advanced ovarian cancer who underwent CRS plus HIPEC between 1998 and 2014, we
      analyzed data for consecutive patients at eight treatment time points: primary
      debulking surgery (PDS); interval debulking surgery after partial response, after
      no response, and after a pathologic complete response to neoadjuvant
      chemotherapy; first recurrence with a progression-free interval >12, <12 months,
      or >12 months in patients who underwent further chemotherapy before CRS and
      HIPEC; and patients who underwent two or more CRS procedures and chemotherapy
      lines before CRS and HIPEC. RESULTS: The 511 enrolled patients underwent 3373
      procedures; 72.6% achieved complete cytoreduction, with an overall major
      morbidity of 17.4%. At a median follow-up of 53.8 months, overall survival (OS)
      was 54.2 months (95% confidence interval [CI] 44-58.4) and progression-free (PFS)
      survival was 16.6 months (95% CI 14.7-19.1). Outcome analysis in patients in whom
      CRS plus HIPEC was used for primary advanced cancer or recurrent ovarian cancer
      showed significant differences in OS and PFS according to the time points
      analyzed. Multivariate analysis identified completeness of CRS, Peritoneal Cancer
      Index, and the times when patients underwent CRS plus HIPEC as independent
      prognostic factors. CONCLUSIONS: This selective information on survival should
      help in interpreting the findings from ongoing randomized studies focusing on CRS
      plus HIPEC in patients with advanced ovarian cancer.

PMID- 27896513
TI  - Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell
      Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach
      for cT4b Patients.
AB  - BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that
      patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should
      be either included in clinical trials or treated with a nonsurgical approach.
      However, surgery may be feasible in selected patients with adequate safety
      margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the
      prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS:
      Of the 18,910 patients with previously untreated first primary OSCC identified
      between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received
      initial treatment with surgery, whereas 165 (34 %) were initially treated with a
      nonsurgical approach. Of the latter group, 78 patients subsequently underwent
      surgery. A 5-year disease-specific survival (DSS) >=45 % was considered as a
      favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates
      were observed in cT4b patients initially treated with surgery (vs. nonsurgery;
      DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants
      initially treated with surgery, patients with cN0-2 disease had better 5-year
      survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %;
      cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients
      who initially received a nonsurgical treatment, subjects who subsequently
      underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is
      performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases
      showing a good prognosis. Patients who initially received a nonsurgical approach
      can subsequently be treated with surgery and achieve favorable outcomes.

PMID- 27896514
TI  - Tumor Infiltrating Mast Cells (TIMs) Confers a Marked Survival Advantage in
      Nonmetastatic Clear-Cell Renal Cell Carcinoma.
AB  - PURPOSE: The role played by the innate immune system in determining the clinical
      outcome of clear-cell renal cell carcinoma (ccRCC) was still blurred. This study
      was designed to investigate the prognostic significance of tumor infiltrating
      mast cells (TIMs) in ccRCC. METHODS: The study retrospectively enrolled a
      training set (474 patients) and a validation set (188 patients) with
      nonmetastasis (pT1-4N0M0) ccRCC from two institutional medical centers of China.
      TIMs was evaluated by immunohistochemical staining of tryptase and its
      association with clinicopathologic features and prognosis were evaluated.
      RESULTS: In ccRCC tissues, TIMs ranged from 0 to 103 cells/mm2 and 0 to 113
      cells/mm2 in the training set and validation set, respectively. TIMs was
      negatively correlated with tumor size (P < 0.001 and P < 0.001, respectively),
      pathological T stage (P = 0.005 and P = 0.007, respectively) and Fuhrman grade (P
      < 0.001 and P < 0.001, respectively). Patients with abundant TIMs infiltration
      showed significantly longer cancer-specific survival in the training cohort and
      the validation cohort (P < 0.001 and P < 0.001). Patients with abundant mast cell
      infiltration showed significantly longer overall survival in the TCGA cohort (P <
      0.001). Moreover, multivariate analysis identified TIMs as an independent
      prognostic factor for cancer-specific survival (CSS) and relapse-free survival
      (RFS). Also, TIMs was significantly correlated with CSS and RFS of the mediate
      and high-risk patients in the training cohort and the validation cohort.
      CONCLUSIONS: TIMs density is a powerful independent prognostic factor for CSS and
      RFS in patients with nonmetastasis (pT1-4N0M0) ccRCC.

PMID- 27896515
TI  - Outcome After Sentinel Lymph Node Dissection in Vulvar Cancer: A Subgroup
      Analysis of the AGO-CaRE-1 Study.
AB  - PURPOSE: Analyzing the large patient cohort of the multicenter AGO-CaRE-1 study,
      we compared isolated sentinel lymph node dissection (SLND) with radical lymph
      node dissection (LND) of the groin in relation to recurrence rates and survival.
      METHODS: The AGO-CaRE-1 study retrospectively collected data on treatment
      patterns and follow-up of vulvar cancer patients [International Federation of
      Gynecology and Obstetrics (FIGO) stage >=1B] treated at 29 gynecologic cancer
      centers between 1998 and 2008. This subgroup analysis evaluated the influence of
      SLND alone on progression-free survival (PFS) and overall survival (OS). RESULTS:
      In 487 (63.1%) of 772 included patients with tumors smaller than 4 cm, an LND was
      performed and no metastatic lymph nodes were detected (LN0). Another 69/772
      (8.9%) women underwent SLND alone, showing a negative SLN (SLN0). Tumors in the
      LN0 group were larger and showed a deeper invasion (LN0 vs. SLN0 tumor diameter:
      20.0 vs. 13.0 mm, p < 0.001; depth of invasion: 4.0 vs. 3.0 mm, p = 0.002). After
      a median follow-up of 33 months (0-156), no significant differences in relation
      to isolated groin recurrence rates (SLN0 3.0% vs. LN0 3.4%, p = 0.845) were
      detected. Similarly, univariate 3-year PFS analysis showed no significant
      differences between both groups (SLN0 82.7% vs. LN0 77.6%, p = 0.230). A
      multivariate Cox regression analysis, including tumor diameter, depth of
      invasion, age, grading, and lymphovascular space invasion was performed: PFS
      [hazard ratio (HR) 0.970, 95% confidence interval (CI) 0.517-1.821] and OS (HR
      0.695, 95% CI 0.261-1.849) did not differ significantly between both cohorts.
      CONCLUSION: This subgroup analysis of the large AGO-CaRE-1 study showed similar
      results for groin LND and SLND alone with regard to recurrence rates and survival
      in node-negative patients with tumors <4 cm.

PMID- 27896516
TI  - The Differential Impact of Body Mass Index and the Feature of Metabolic Syndrome
      on Oncological Outcomes Following Different Surgical Procedures in Japanese Men
      with Prostate Cancer.
AB  - PURPOSE: This study aimed to examine the differential impact of body mass index
      and the feature of metabolic syndrome (MetS; obesity, hypertension, diabetes
      mellitus, and dyslipidemia) on biochemical recurrence (BCR) following radical
      prostatectomy (RP) treatment for prostate cancer using different surgical
      procedures. METHODS: This study included 283 Japanese patients with clinically
      localized prostate cancer who were treated with RP between 2008 and 2012. The
      prognostic significance of overweight and the feature of MetS were analyzed
      according to surgical procedures. RESULTS: BCR occurred in 68/283 (24.0%) men.
      Overweight and the feature of MetS were predictors of BCR in patients who had
      undergone open RP (ORP), but not in those treated with laparoscopic surgery.
      Multivariate analyses incorporating preoperative and postoperative risk factors
      revealed that overweight and the feature of MetS were independent BCR risk
      factors when treated with ORP. CONCLUSIONS: In Japanese men, overweight and the
      feature of MetS were associated with worse outcomes following RP, particularly
      ORP, compared with those following laparoscopic surgery. These results suggest
      that laparoscopic surgery can overcome the surgical challenges associated with
      abdominal obesity.

PMID- 27896517
TI  - Surgical Resection of Cerebral Metastases Leads to Faster Resolution of
      Peritumoral Edema than Stereotactic Radiosurgery: A Volumetric Analysis.
AB  - BACKGROUND: Surgical resection and stereotactic radiosurgery (SRS) are well
      established treatment options for selected patients with oligo-brain metastases
      (BMs). The dynamics of edema resolution with each treatment method have not been
      well characterized. METHODS: Of 389 patients treated for BMs between 2012 and
      2014, this study retrospectively identified 107 patients (150 metastases) who
      underwent either surgery or SRS as a single treatment method for BMs. The two
      groups of patients were matched for clinical parameters. Volumetric assessments
      of the tumor and associated edema were performed before treatment and then 2-3
      months after treatment. RESULTS: In this study, 76 surgical cases were compared
      with 74 cases treated with SRS. The volume of the tumor and surrounding edema was
      significantly greater in the surgery group than in the SRS group. However,
      resolution of edema was significantly more rapid in the surgical group (p <
      0.0001), accompanied by faster weaning from steroids. After a matching process
      based on the propensity of a patient to receive SRS, a subgroup cohort was
      analyzed (mean maximal diameter: 21 mm in the surgical group vs 20.8 mm in the
      SRS group; p = 0.9). At diagnosis, edema volume, but not tumor volume, was
      significantly greater in the surgical group. The resolution of edema 2-3 months
      after treatment was better in the surgical group than in the SRS group (89.6% vs
      71.1% of baseline, respectively; p = 0.09), although this difference did not
      reach the level of significance. CONCLUSIONS: Resolution of tumor-associated
      edema in BMs suitable for either surgery or SRS was significantly faster after
      surgical resection than after SRS. Accordingly, when both treatment options are
      suitable, surgery appears to induce faster resolution of the edema.

PMID- 27896518
TI  - Analysis of Predictors of Resection and Survival in Locally Advanced Stage III
      Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes?
AB  - BACKGROUND: Locally advanced unresectable pancreatic cancer (LAPC) historically
      portends a poor prognosis. FOLFIRINOX and gemcitabine/nab-paclitaxel have proven
      effective in the metastatic setting. We sought to evaluate the outcomes of these
      regimens compared with older regimens in LAPC. METHODS: A retrospective, single
      institutional review of all consecutive LAPC treated with "new" (FOLFIRINOX
      and/or gemcitabine/nab-paclitaxel) and "old" (gemcitabine or 5-FU) chemotherapy
      from 2010 to 2014 was performed. Univariate and multivariate predictors of
      resection and survival were determined. RESULTS: A total of 92 patients (new
      chemotherapy = 61, old chemotherapy = 31) were analyzed, of which 19 (21%)
      underwent eventual resection (median overall survival [OS] = 32 vs. 14.3 months
      for unresected patients, P = 0.0002). For the overall cohort, resection (hazard
      ratio [HR] 0.261, P = 0.014), radiation therapy (HR 0.458, P = 0.004), number of
      lines of chemotherapy (HR 0.486, P = 0.012), and new chemotherapy (HR 0.593 vs.
      old regimens, P = 0.065) were independent predictors of OS on multivariate
      analyses (MVA). On MVA, predictors of eventual resection were head and neck
      tumors (OR 0.307, P = 0.033) or SMA involvement (OR 0.285, P = 0.023). In
      nonresected patients (73), MVA showed treatment with new chemotherapy (HR 0.452,
      P = 0.006), radiation (HR 0.459, P = 0.006), and number of lines of CT (HR 0.705,
      P = 0.013) to be predictors of survival. CONCLUSIONS: In LAPC, use of FOLFIRNOX
      and/or gemcitabine/nab-paclitaxel is associated with improved survival compared
      with older chemotherapy regimens, regardless of eventual resection. Tumor
      location and relationship to certain vasculature are important determinants of
      resection in this cohort.

PMID- 27896521
TI  - PI3K/AKT/mTOR: role in breast cancer progression, drug resistance, and treatment.
AB  - Anti-cancer cancer-targeted therapies are designed to exploit a particular
      vulnerability in the tumor, which in most cases results from its dependence on an
      oncogene and/or loss of a tumor suppressor. Mutations in the phosphoinositide 3
      kinase (PI3K)/AKT/mTOR pathway are freqcuently found in breast cancers and
      associated with cellular transformation, tumorigenesis, cancer progression, and
      drug resistance. Several drugs targeting PI3K/ATK/mTOR are currently in clinical
      trials, mainly in combination with endocrine therapy and anti-HER2 therapy. These
      drugs are the focus of this review.

PMID- 27896519
TI  - Image-guidance technology and the surgical resection of spinal column tumors.
AB  - Precision imaging is paramount to achieving success in surgical resection of many
      spinal tumors, whether the goal involves guiding a surgical cure for primary
      tumors or improving neurological decompression for metastatic lesions. Pre
      operatively, image visualization is intimately involved with defining a clear
      target and surgical planning. Intra-operatively, image-guidance technology allows
      for surgeons to maximize the probability for gross total resection of spinal cord
      tumors and minimize damage to adjacent structures. Through this review, it is
      evident that spinal surgery has undergone significant advancements with the
      continued technological progression of different modalities of imaging guided
      technologies. Sophisticated imaging techniques compliment the surgeon's knowledge
      by providing an intraoperative reference to spinal column anatomy. This review
      discusses research efforts focusing on immersive imaging guided interactions with
      subject specific medical images that could enhance a surgeon's ability to plan
      and perform complex spinal oncology procedures with safety and efficiency.

PMID- 27896520
TI  - Early perfusion MRI predicts survival outcome in patients with recurrent
      glioblastoma treated with bevacizumab and carboplatin.
AB  - Bevacizumab, an anti-angiogenic agent, is FDA-approved for use in patients with
      recurrent glioblastoma multiforme (rGBM). The radiologic evaluation of tumor
      response to bevacizumab is complex and there is no validated method of monitoring
      tumor vascularity during therapy. We evaluated perfusion-weighted MR imaging
      (PWI) in our cohort of patients enrolled in the CABARET trial, which examined the
      effectiveness of bevacizumab with or without carboplatin in patients with rGBM.
      Pre-treatment and early follow-up (4- and 8-week) PWI were used to calculate
      relative cerebral blood volume (rCBV) histogram statistics of the contrast
      enhancing and FLAIR hyperintense tumor volumes. A novel rCBV measurement (load)
      was developed to estimate the total volume of perfused tumor blood vessels.
      Changes in all rCBV measures were examined for correlations with progression-free
      (PFS) and overall survival (OS). All of our 15 patients enrolled in the CABARET
      trial were included. Median PFS and OS were 23 and 45 weeks respectively. Kaplan
      Meier analysis of pre-treatment PWI revealed an 18 week reduction in median OS in
      patients with high tumor rCBV (p = 0.031). Changes in rCBV measures, especially
      load, correlated significantly with PFS and OS at both follow-up time-points.
      Patients with the greatest reduction in rCBVload by 8-weeks of therapy had a
      significantly increased median OS (30 weeks; p = 0.013). PWI may be of
      significant clinical utility in managing patients with rGBM, particularly those
      treated with anti-angiogenic agents such as bevacizumab. These findings need to
      be confirmed prospectively in larger studies.

PMID- 27896524
TI  - Guidelines on homocystinurias and methylation defects: a harmonized approach to
      diagnosis and management.

PMID- 27896525
TI  - From solidarity to autonomy: towards a redefinition of the parameters of the
      notion of autonomy.
AB  - Starting from examples of concrete situations in France, I show that autonomy and
      solidarity can coexist only if the parameters of autonomy are redefined. I show
      on the one hand that in situations where autonomy is encouraged, solidarity
      nevertheless remains at the foundation of their practices. On the other hand, in
      situations largely infused with family solidarity, the individual autonomy may be
      put in danger. Yet, based on my ethnographic observations regarding clinical
      encounters and medical secrecy, I show that while solidarity may endanger
      individual autonomy, it does not necessarily endanger autonomy itself. The social
      practices observable in France reflect the reality of an autonomy that goes
      beyond the individual, a reality that involves a collective subject and includes
      solidarity. The opposition between these two values can then be resolved if the
      content of the notion of autonomy is understood to be dependent on its cultural
      context of application and on its social use.

PMID- 27896522
TI  - Tapering biologics in rheumatoid arthritis: a pragmatic approach for clinical
      practice.
AB  - Optimal rheumatoid arthritis (RA) therapy in daily clinical practice is based on
      the treat-to-target strategy. Quicker escalation of therapy and earlier
      introduction of biological disease-modifying anti-rheumatic drugs have led to
      improved outcomes in RA. However, chronic immunosuppressive therapy is associated
      with adverse events and higher costs. In addition, our patients frequently
      express a desire for lower dosing and drug holidays. Current clinical practice
      guidelines from the American College of Rheumatology and European League Against
      Rheumatism suggest that rheumatologists consider tapering treatment after
      achieving remission. However, the optimal approach for tapering therapy in RA,
      specifically de-escalation of biologics, remains unknown. This clinical review
      discusses biologic tapering strategies in RA. We draw our recommendations for
      everyday clinical practice from the most recent observational, pragmatic, and
      controlled clinical trials on de-escalation of biologics in RA. For each
      biologic, we highlight clinically relevant outcomes, such as flare rates,
      recapture of the disease control with retreatment, radiographic progression, side
      effects, and functional impact. We discuss the use of musculoskeletal ultrasound
      to select patients for successful tapering. In conclusion, we provide the reader
      with a practical guide for tapering biologics in the rheumatology clinic.

PMID- 27896523
TI  - A CD57+ CTL Degranulation Assay Effectively Identifies Familial Hemophagocytic
      Lymphohistiocytosis Type 3 Patients.
AB  - PURPOSE: Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is a genetic
      disorder that results in immune dysregulation. It requires prompt and accurate
      diagnosis. A natural killer (NK) cell degranulation assay is often used to screen
      for FHL3 patients. However, we recently encountered two cases of late-onset FHL3
      carrying novel UNC13D missense mutations: in these cases, the degranulation
      assays using freshly isolated and interleukin (IL)-2-activated NK cells yielded
      contradictory results. Since the defective degranulation of CD57+ cytotoxic T
      lymphocytes (CTLs) in these cases was helpful for making the diagnosis, we
      assessed whether the CD57+ CTL degranulation assay more effectively identified
      FHL3 patients than the NK cell assays. METHODS: Forty additional patients with
      hemophagocytic lymphohistiocytosis were prospectively screened for FHL3 by
      measuring the perforin expression in NK cells and the expression of Munc13-4,
      syntaxin-11, and Munc18-2 in platelets and by performing NK cell and CTL
      degranulation assays. The results were confirmed by genetic analysis. RESULTS:
      The freshly isolated NK cell degranulation assay detected FHL3 patients with high
      sensitivity (100%) but low specificity (71%). The IL-2-stimulated NK cell assay
      had improved specificity, but 3 out of the 31 non-FHL3 patients still showed
      degranulation below the threshold level. The CD57+ CTL degranulation assay
      identified FHL3 patients with high sensitivity and specificity (both 100%).
      CONCLUSIONS: The CD57+ CTL degranulation assay more effectively identified FHL3
      patients than the NK cell-based assays.

PMID- 27896526
TI  - Solidarity, justice, and recognition of the other.
AB  - Solidarity has for a long time been referred to as the core value underpinning
      European health and welfare systems. But there has been debate in recent years
      about whether solidarity, with its alleged communitarian content, can be
      reconciled with the emphasis on individual freedom and personal autonomy. One may
      wonder whether there is still a place for solidarity, and whether the concept of
      justice should be embraced to analyse the moral issues regarding access to health
      care. In this article, I will answer this question by analysing the normative
      foundations of the concept of justice, followed by a deeper examination of the
      concept of solidarity in continental philosophy. More specifically, I will
      compare the philosophical traditions rooted in Kant (with emphasis on autonomy
      and individual rights) to approaches rooted in Hegel (with emphasis on individual
      relations of recognition). In addition, I will present the work of Avishai
      Margalit on the decent society to criticize a predominantly liberal approach to
      access to health care. The importance of solidarity lies particularly in its
      emphasis on relational aspects and the role of recognition in care practices,
      which are usually ignored in liberal approaches to justice. However, the article
      will argue that solidarity is not an alternative to a rights-based concept of
      justice, but must be considered as a necessary complement to it.

PMID- 27896527
TI  - An enzyme kinetics study of the pH dependence of chloride activation of oxygen
      evolution in photosystem II.
AB  - Oxygen evolution by photosystem II (PSII) involves activation by Cl- ion, which
      is regulated by extrinsic subunits PsbQ and PsbP. In this study, the kinetics of
      chloride activation of oxygen evolution was studied in preparations of PSII
      depleted of the PsbQ and PsbP subunits (NaCl-washed and Na2SO4/pH 7.5-treated)
      over a pH range from 5.3 to 8.0. At low pH, activation by chloride was followed
      by inhibition at chloride concentrations >100 mM, whereas at high pH activation
      continued as the chloride concentration increased above 100 mM. Both activation
      and inhibition were more pronounced at lower pH, indicating that Cl- binding
      depended on protonation events in each case. The simplest kinetic model that
      could account for the complete data set included binding of Cl- at two sites, one
      for activation and one for inhibition, and four protonation steps. The intrinsic
      (pH-independent) dissociation constant for Cl- activation, K S, was found to be
      0.9 +/- 0.2 mM for both preparations, and three of the four pK as were
      determined, with the fourth falling below the pH range studied. The intrinsic
      inhibition constant, K I, was found to be 64 +/- 2 and 103 +/- 7 mM for the NaCl
      washed and Na2SO4/pH7.5-treated preparations, respectively, and is considered in
      terms of the conditions likely to be present in the thylakoid lumen. This enzyme
      kinetics analysis provides a more complete characterization of chloride and pH
      dependence of O2 evolution activity than has been previously presented.

PMID- 27896528
TI  - Low-level laser therapy as an adjunct to conventional therapy in the treatment of
      diabetic foot ulcers.
AB  - Foot ulcers are serious complications of diabetes mellitus (DM) and are known to
      be resistant to conventional treatment. This study was conducted to evaluate the
      efficacy of low-level laser therapy (LLLT) for the treatment of diabetic foot
      ulcers in a tertiary care centre (Department of Surgery, Mahatma Gandhi Memorial
      Medical College and Maharaja Yashwantrao Hospital, A.B. Road, Indore). A total of
      30 patients with type 2 DM having Meggitt-Wagner grade I foot ulcers of more than
      6 weeks duration with negative culture were studied. Patients were randomized
      into two groups of 15 each. Patients in study group received LLLT (660 +/- 20 nm,
      3 J/cm2) along with conventional therapy and those in control group were treated
      with conventional therapy alone. The primary outcome measure was the absolute and
      relative wound size reduction at 2 weeks compared to the baseline parameter.
      Percentage ulcer area reduction was 37 +/- 9% in the LLLT group and 15 +/- 5.4%
      in the control group (p < 0.001). For ~75% of wounds of the treatment group,
      wound area reduction of 30-50% was observed. In contrast, for the control group,
      ~80% of wounds showed a wound area reduction of <20% on day 15. Further, the
      wounds with initial wound area 1000-2000 mm2 seems to have better final outcome
      than the groups with larger areas. The treated groups showed higher amount of
      granulation than the control group. The results suggest that LLLT is beneficial
      as an adjunct to conventional therapy in the treatment of diabetic foot ulcers.

PMID- 27896529
TI  - Acetaldehyde kinetics of enological yeast during alcoholic fermentation in grape
      must.
AB  - Acetaldehyde strongly binds to the wine preservative SO2 and, on average, causes
      50-70 mg l-1 of bound SO2 in red and white wines, respectively. Therefore, a
      reduction of bound and total SO2 concentrations necessitates knowledge of the
      factors that affect final acetaldehyde concentrations in wines. This study
      provides a comprehensive analysis of the acetaldehyde production and degradation
      kinetics of 26 yeast strains of oenological relevance during alcoholic
      fermentation in must under controlled anaerobic conditions. Saccharomyces
      cerevisiae and non-Saccharomyces strains displayed similar metabolic kinetics
      where acetaldehyde reached an initial peak value at the beginning of
      fermentations followed by partial reutilization. Quantitatively, the range of
      values obtained for non-Saccharomyces strains greatly exceeded the variability
      among the S. cerevisiae strains tested. Non-Saccharomyces strains of the species
      C. vini, H. anomala, H. uvarum, and M. pulcherrima led to low acetaldehyde
      residues (<10 mg l-1), while C. stellata, Z. bailii, and, especially, a S. pombe
      strain led to large residues (24-48 mg l-1). Acetaldehyde residues in S.
      cerevisiae cultures were intermediate and less dispersed (14-34 mg l-1). Addition
      of SO2 to Chardonnay must triggered significant increases in acetaldehyde
      formation and residual acetaldehyde. On average, 0.33 mg of residual acetaldehyde
      remained per mg of SO2 added to must, corresponding to an increase of 0.47 mg of
      bound SO2 per mg of SO2 added. This research demonstrates that certain non
      Saccharomyces strains display acetaldehyde kinetics that would be suitable to
      reduce residual acetaldehyde, and hence, bound-SO2 levels in grape wines. The
      acetaldehyde formation potential may be included as strain selection argument in
      view of reducing preservative SO2 concentrations.

PMID- 27896530
TI  - Maxillary sinus mucocele: predisposing factors, clinical presentations, and
      treatment.
AB  - PURPOSE: Maxillary sinus mucocele (MSM) is uncommon lesion and has many
      presenting features. The aim of this study was to detect the possible
      predisposing factors, clinical characteristics, and to assess the efficacy of
      trans-nasal endoscopic treatment of this lesion. METHODS: This retrospective
      multicenter study was conducted on 36 patients with MSM, the diagnosis of the
      disease was based on computed tomographic criteria. The patients' history,
      presenting features, and surgical management were reviewed. All patients were
      followed up postoperatively for at least 3 years. RESULTS: Chronic sinusitis,
      previous surgery, allergic rhinitis, and nasal trauma may be implicated as
      predisposing factors for the disease. However, in some patients (56%) the cause
      may remain uncertain. MSM may present with unilateral cheek pain, heaviness,
      swelling, numbness, hemifacial pain, nasal obstruction, nasal discharge, and/or
      proptosis. All patients were treated with trans-nasal endoscopic marsupialization
      through the middle meatus, patients with large MSM showed bulged medial maxillary
      wall, and they needed to empty the fluid through inferior antrostomy to
      facilitate introduction of the instruments to the middle meatus. All patients
      reported resolution of their symptoms, and none required revision surgery through
      the follow-up period. CONCLUSIONS: MSM has several predisposing factors such as
      chronic sinusitis, previous surgery, allergic rhinitis and nasal trauma. However,
      some patients have no identifiable cause. The disease can present with a variety
      of symptoms which are usually related to their expansion and subsequent pressure
      on the surrounding structures. Trans-nasal endoscopic approach is an effective
      and safe method for treatment of the lesion.

PMID- 27896532
TI  - Answer to the Letter to the Editor of Y. Zhao et al. concerning "Percutaneous
      versus traditional and paraspinal posterior open approaches for treatment of
      thoracolumbar fractures without neurologic deficit: a meta-analysis'' by Sun XY,
      Zhang XN, Hai Y: Eur Spine J (2016); doi:10.1007/s00586-016-4818-4.

PMID- 27896531
TI  - Primary intramedullary hydatid cyst: a case report and literature review.
AB  - Intramedullary hydatid cyst is extremely rare. We present a case of
      pathologically confirmed primary intramedullary hydatid cyst in an otherwise
      healthy patient. A 17-year-old boy presented with lumbar pain, weakness, and
      numbness in both lower limbs, and urinate difficulty interrupted for 2 years. The
      patient had no other signs of systemic hydatid cyst disease. An intramedullary
      cystic lesion was identified with magnetic resonance imaging and was shown to be
      a hydatid cyst by histopathologic examination after the surgical removal.
      Although extremely rare, primary intramedullary hydatid cyst pathology might be
      the cause of lumbar pain, weakness, and numbness in both lower limbs for those
      living in endemic areas. Surgical removement is feasible and effective for
      intramedullary hydatid cyst.

PMID- 27896533
TI  - Characteristics of higher-order aberrations and anterior segment tomography in
      patients with pathologic myopia.
AB  - PURPOSE: To investigate prospectively the characteristics in the higher-order
      aberrations and anterior segment tomography in patients with pathologic myopia.
      METHODS: One hundred and twelve consecutive highly myopic patients (mean age 43.4
      +/- 9.3 years, spherical equivalent of refractive error >=8 D and an axial length
      >=26.5 mm) were studied. Thirty-seven emmetropic individuals (mean age 37.0 +/-
      14.5 years, spherical equivalent of refractive error <= +/-1 D) were analyzed as
      controls. The ocular and cornea higher-order aberrations were measured using a
      Hartmann-Shack wavefront sensor (KR-1W; Topcon Corporation, Tokyo, Japan). The
      crystalline lens rise, the angle-to-angle, and the white-to-white values were
      measured using anterior segment OCT (SS-1000; Tomey Corporation, Nagoya, Japan).
      The mean curvature of the anterior corneal surface, the thickness at the thinnest
      central corneal point, the location of the central corneal point, the corneal
      volume, the anterior chamber volume, and the anterior chamber depth were measured
      using the Pentacam HR (Oculus, Inc., Wetzlar, Germany). RESULTS: The ocular total
      higher-order aberration for 4-mm pupil, the ocular spherical aberrations, and
      internal spherical aberration for 6-mm pupil were significantly higher in highly
      myopic eyes than in the emmetropic controls. The crystalline lens rise was
      significantly smaller in highly myopic eyes than in the emmetropic controls. The
      anterior chamber depth and the anterior chamber volume were significantly larger
      in highly myopic eyes than in the emmetropic controls. CONCLUSION: Highly myopic
      eyes had higher-order aberrations than emmetropic eyes because of the increasing
      internal aberrations.

PMID- 27896534
TI  - Reactions and Strategies of German Catholic Priests to Cope with Phases of
      Spiritual Dryness.
AB  - We investigated strategies of 763 Catholic priests (response rate 36%) to deal
      with phases of spiritual dryness, specifically their reactions toward these
      feelings, and which strategies were used. Most priests have found strategies to
      cope with feelings of spiritual dryness. Those who have managed to overcome these
      phases were stimulated "all the more to help others" and experienced "deeper
      spiritual clarity and depth." Whatever strategy was chosen (we differentiated
      eight strategies in various combinations), there were no significant differences
      for priests' self-efficacy expectation, transcendence perception or life
      satisfaction. Instead, we found significant differences for social support (F =
      6.5; p < 0.0001) and somatization (F = 3.4; p = 0.002).

PMID- 27896536
TI  - Erratum to: Health-exploring complexity: an interdisciplinary systems approach
      HEC2016 : 28 August-2 September 2016, Munich, Germany.

PMID- 27896535
TI  - Generation of gene edited birds in one generation using sperm transfection
      assisted gene editing (STAGE).
AB  - Generating transgenic and gene edited mammals involves in vitro manipulation of
      oocytes or single cell embryos. Due to the comparative inaccessibility of avian
      oocytes and single cell embryos, novel protocols have been developed to produce
      transgenic and gene edited birds. While these protocols are relatively efficient,
      they involve two generation intervals before reaching complete somatic and
      germline expressing transgenic or gene edited birds. Most of this work has been
      done with chickens, and many protocols require in vitro culturing of primordial
      germ cells (PGCs). However, for many other bird species no methodology for long
      term culture of PGCs exists. Developing methodologies to produce germline
      transgenic or gene edited birds in the first generation would save significant
      amounts of time and resource. Furthermore, developing protocols that can be
      readily adapted to a wide variety of avian species would open up new research
      opportunities. Here we report a method using sperm as a delivery mechanism for
      gene editing vectors which we call sperm transfection assisted gene editing
      (STAGE). We have successfully used this method to generate GFP knockout embryos
      and chickens, as well as generate embryos with mutations in the doublesex and mab
      3 related transcription factor 1 (DMRT1) gene using the CRISPR/Cas9 system. The
      efficiency of the method varies from as low as 0% to as high as 26% with multiple
      factors such as CRISPR guide efficiency and mRNA stability likely impacting the
      outcome. This straightforward methodology could simplify gene editing in many
      bird species including those for which no methodology currently exists.

PMID- 27896537
TI  - A serious misinterpretation of a consistent inverse association of statin use
      with glioma across 3 case-control studies.

PMID- 27896538
TI  - Reply to Greenland: A serious misinterpretation of a consistent inverse
      association of statin use with glioma across 3 case-control studies.

PMID- 27896539
TI  - Why Health and Social Care Support for People with Long-Term Conditions Should be
      Oriented Towards Enabling Them to Live Well.
AB  - There are various reasons why efforts to promote "support for self-management"
      have rarely delivered the kinds of sustainable improvements in healthcare
      experiences, health and wellbeing that policy leaders internationally have hoped
      for. This paper explains how the basis of failure is in some respects built into
      the ideas that underpin many of these efforts. When (the promotion of) support
      for self-management is narrowly oriented towards educating and motivating
      patients to adopt the behaviours recommended for disease control, it implicitly
      reflects and perpetuates limited and somewhat instrumental views of patients. It
      tends to: restrict the pursuit of respectful and enabling 'partnership working';
      run the risk of undermining patients' self-evaluative attitudes (and then of
      failing to notice that as harmful); limit recognition of the supportive value of
      clinician-patient relationships; and obscure the practical and ethical tensions
      that clinicians face in the delivery of support for self-management. We suggest
      that a focus on enabling people to live (and die) well with their long-term
      conditions is a promising starting point for a more adequate conception of
      support for self-management. We then outline the theoretical advantages that a
      capabilities approach to thinking about living well can bring to the development
      of an account of support for self-management, explaining, for example, how it can
      accommodate the range of what matters to people (both generally and more
      specifically) for living well, help keep the importance of disease control in
      perspective, recognize social influences on people's values, behaviours and
      wellbeing, and illuminate more of the rich potential and practical and ethical
      challenges of supporting self-management in practice.

PMID- 27896541
TI  - Gomisin N Decreases Inflammatory Cytokine Production in Human Periodontal
      Ligament Cells.
AB  - Gomisin N, which is a lignan isolated from Schisandra chinensis, has some
      pharmacological effects. However, the anti-inflammatory effects of gomisin N on
      periodontal disease are uncertain. The aim of this study was to examine the
      effect of gomisin N on inflammatory mediator production in tumor necrosis factor
      (TNF)-alpha-stimulated human periodontal ligament cells (HPDLC). Gomisin N
      inhibited interleukin (IL)-6, IL-8, CC chemokine ligand (CCL) 2, and CCL20
      production in TNF-alpha-stimulated HPDLC in a dose-dependent manner. Moreover, we
      revealed that gomisin N could suppress extracellular signal-regulated kinase
      (ERK) and c-Jun N terminal kinase (JNK) phosphorylation in TNF-alpha-stimulated
      HPDLC though protein kinase B (Akt) phosphorylation was not suppressed by gomisin
      N treatment. In summary, gomisin N might exert anti-inflammatory effects by
      attenuating cytokine production in periodontal ligament cells via inhibiting the
      TNF-alpha-stimulated ERK and JNK pathways activation.

PMID- 27896540
TI  - Variations in the anatomy of the vertebral artery cervical loop segment - a
      potential predisposing factor for traumatic basal subarachnoid hemorrhage?
AB  - Fatal traumatic basal subarachnoid hemorrhage (TBSAH) is a characteristic
      forensic pathological entity, the investigation of which requires special
      techniques. In Liverpool, post-mortem room angiography is undertaken, followed by
      complete removal of the vertebral arteries and histological examination. It has
      been observed that the arterial anatomy can be highly variable, particularly the
      length and course of the loop segments located between the C2 vertebra and the
      dura. In a number of cases of TBSAH the loop segments of torn vessels have
      appeared relatively short. Having observed this phenomenon subjectively in our
      case work, a radiological study was undertaken with the aim of quantifying
      vertebral artery loop anatomy variation in a 'normal' population. Multiphase post
      mortem computed tomography angiography (MPMCTA) scans of 98 subjects were
      reviewed and the lengths of the different portions of the loop segments (foramen
      magnum to the upper border of C1, between C1 and C2, and the bony foramina
      themselves) of each vertebral artery were measured using semi-automated vessel
      analysis software. The measurements obtained provide objective evidence of marked
      anatomical variation, with some loop segments more than twice the length of
      others. These results are important because a short vertebral artery loop segment
      might be a significant factor in predisposing an individual to TBSAH following a
      blow to the head or neck.

PMID- 27896542
TI  - Immunomodulatory Effects of Adjuvants CPG, MPLA, and BCG on the Derp2-Induced
      Acute Asthma at Early Life in an Animal Model of BALB/c Mice.
AB  - The Th1- and Treg cell-related immune responses play key roles in the modulation
      of Th2 cell-related allergic disorders. The aim was to evaluate the effects of
      CPG, MPLA, and BCG on the number of Th1-, Th2-, and Treg cell-related parameters
      in an animal model of asthma. BALB/c mice were divided into five groups and
      immunized subcutaneously (SC) on days 1, 15, and 22 with allergen Derp2. Three
      groups of mice were pretreated SC on days 0, 14, and 21 with CPG, CPG + MPLA, or
      CPG + BCG. All mice were then challenged intranasally with Derp2 on days 28-37.
      Blood samples were collected from the retro-orbital sinus, on days 0, 23, and 40.
      The serum levels of IL-4, IFN-gamma, IgE, and IgG2a were measured using ELISA
      technique. The blood number of Th1 and Treg cells was determined using flow
      cytometry. At the sensitization phase, the number of Th1 and the serum levels of
      IFN-gamma and IgG2a were significantly increased in the Derp2-sensitized group
      pretreated with CPG plus MPLA, and the number of Treg cells was significantly
      elevated in Derp2-sensitized mice pretreated with CPG or CPG plus MPLA as
      compared with that in Derp2-sensitized control mice. At the challenge phase, the
      number of Th1 was significantly elevated in Derp2-sensitized mice pretreated with
      CPG plus MPLA, CPG plus BCG, or CPG; the count of Treg cells was significantly
      increased in Derp2-sensitized mice pretreated with CPG plus BCG group; and the
      levels of IFN-gamma and IgG2a were significantly enhanced in the Derp2-sensitized
      group pretreated with CPG plus MPLA in comparison with those in Derp2-sensitized
      control mice. The scores of inflammation and mucus secretion in the lung were
      significantly decreased in the Derp2-sensitized group pretreated with CPG, BCG,
      and CPG plus MPLA in comparison with those in the Derp2-sensitized control group.
      These results showed that BCG, MPLA, and CPG modulate Th1-, Th2-, and Treg
      related parameters and ameliorate lung inflammatory parameters in a mouse model
      of asthma.

PMID- 27896544
TI  - Mourning the Death of a Foreign Child.

PMID- 27896543
TI  - Vitamin K antagonists: relative strengths and weaknesses vs. direct oral
      anticoagulants for stroke prevention in patients with atrial fibrillation.
AB  - Vitamin K antagonists (VKAs) have been the mainstay of anticoagulation therapy
      for more than 50 years. VKAs are mainly used for the prevention of stroke in
      patients with atrial fibrillation (AF) and the treatment and secondary prevention
      of venous thromboembolism. In the past 5 years, four new agents-the direct factor
      Xa inhibitors apixaban, edoxaban and rivaroxaban and the direct thrombin
      inhibitor dabigatran [collectively known as direct oral anticoagulants (DOACs) or
      non-VKA oral anticoagulants]-have been approved for these and other indications.
      Despite these new treatment options, the VKA warfarin currently remains the most
      frequently prescribed oral anticoagulant. The availability of DOACs provides an
      alternative management option for patients with AF, especially when the treating
      physician is hesitant to prescribe a VKA owing to associated limitations, such as
      food and drug interactions, and concerns about bleeding complications. Currently
      available real-world evidence shows that DOACs have similar or improved
      effectiveness and safety outcomes compared with warfarin. Treatment decisions on
      which DOAC is best suited for which patient to maximize safety and effectiveness
      should take into account not only clinically relevant patient characteristics but
      also patient preference. This article reviews and highlights real and perceived
      implications of VKAs for the prevention of stroke in patients with non-valvular
      AF, with specific reference to their strengths and weaknesses compared with
      DOACs.

PMID- 27896545
TI  - Safety and tolerability of pasireotide long-acting release in acromegaly-results
      from the acromegaly, open-label, multicenter, safety monitoring program for
      treating patients who have a need to receive medical therapy (ACCESS) study.
AB  - PURPOSE: Pasireotide long-acting release is a somatostatin analog that is
      indicated for treatment of patients with acromegaly. This analysis documents the
      safety of pasireotide long-acting release in patients with acromegaly enrolled in
      the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). METHODS: ACCESS is
      an open-label, multicenter, single-arm, expanded-treatment protocol designed to
      provide patients access to pasireotide long-acting release pending regulatory
      approval. Patients received pasireotide long-acting release 40 mg administered
      intramuscularly every 28 days. The primary outcome was the proportion of patients
      having a treatment-emergent grade >=3 or serious adverse event. Efficacy data
      were not collected. RESULTS: Forty-four adult patients with active acromegaly
      were enrolled in the study for an average of 37.6 weeks (range, 4-70 weeks).
      Twenty-five grade >=3 treatment-emergent adverse events were reported in 11
      patients (25.0 %), 3 of whom (27.3 %) experienced grade >=3 hyperglycemia. In
      patients treated with pasireotide long-acting release for >=3 months (n = 42),
      mean glycated hemoglobin and fasting plasma glucose levels increased
      significantly from 5.9 % and 100.4 mg/dL at baseline to 6.8 % and 135.9 mg/dL at
      3 months, respectively. Ten patients (22.7 %) were treated with pasireotide long
      acting release for >=15 months, after which mean glycated hemoglobin and fasting
      plasma glucose levels were 6.3 % and 123 mg/dL, respectively. Twenty-one patients
      (48 %) initiated antidiabetic medication. CONCLUSIONS: Grade >=3 adverse events
      (primary outcome) were reported in 25.0 % of acromegaly patients treated with
      pasireotide long-acting release in a clinical setting. Hyperglycemia-related
      adverse events were reported in 45.5 % of patients, but were typically
      manageable, supporting the role of pasireotide long-acting release as a safe
      treatment option for acromegaly patients.

PMID- 27896546
TI  - JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in
      an experimental model of cachexia.
AB  - Oncologic patients subjected to chemotherapy frequently present aphagia,
      malnutrition, and cachexia. The purpose of this study was to investigate whether
      selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951
      could antagonize body weight loss and wasting induced by cisplatin administration
      in rats. The three growth hormone secretagogues behaved as full agonists of the
      growth hormone secretagogues receptor both in terms of ability to stimulate
      calcium mobilization in Chinese hamster ovary cells and stimulation of growth
      hormone release in neonatal rats. Adult rats were (i) treated with vehicle
      throughout (controls), or (ii) treated with cisplatin (days 1-3) and a growth
      hormone secretagogues or vehicle, (days 1-12). Body weight and food consumption
      were measured daily. Although all growth hormone secretagogues caused initial
      transient acute increases in food intake, the total amount of food eaten by
      controls and growth hormone secretagogues treated groups over the 12 experimental
      days was not significantly different. All groups pre-treated with cisplatin lost
      up to 5-10 % body weight in the first 4 days; they subsequently gained weight at
      a rate comparable with controls. Interestingly, rats which received JMV2894
      demonstrated a faster gain in body weight than any other growth hormone
      secretagogues treated group and at the end of the protocol reached a weight
      similar to that of controls. JMV2894 did not stimulate perirenal and epididymal
      fat accumulation but reduced MuRF mRNA levels in skeletal muscles. In conclusion,
      our findings demonstrate that JMV2894 antagonizes cisplatin induced weight loss
      in rats and may prove useful in antagonizing cachexia associated with cancer and
      chemotherapy in humans.

PMID- 27896547
TI  - Chemical Analysis of a "Miller-Type" Complex Prebiotic Broth : Part II: Gas, Oil,
      Water and the Oil/Water-Interface.
AB  - We have analyzed the chemical variety obtained by Miller-Urey-type experiments
      using nuclear magnetic resonance (NMR) spectroscopy and coherent anti-Stokes
      Raman scattering (CARS) spectroscopy, gas chromatography followed by mass
      spectrometry (GC/MS) and two-dimensional gas chromatography followed by mass
      spectrometry (GCxGC/MS). In the course of a running Miller-Urey-type experiment,
      a hydrophobic organic layer emerged besides the hydrophilic aqueous phase and the
      gaseous phase that were initially present. The gas phase mainly consisted of
      aromatic compounds and molecules containing C=C or C=N triple bonds. The
      hydrophilic phase contained at least a few thousands of different molecules,
      primarily distributed in a range of 50 and 500 Da. The hydrophobic phase is
      characterized by carbon-rich, oil-like compounds and their amphiphilic
      derivatives containing oxygen with tensioactive properties. The presence of a
      wide range of oxidized molecules hints to the availability of oxygen radicals. We
      suggest that they intervene in the formation of alkylated polyethylene glycol
      (PEG) in the oil/water interface. CARS spectroscopy revealed distinct vibrational
      molecular signatures. In particular, characteristic spectral bands for cyanide
      compounds were observed if the broth was prepared with electric discharges in the
      gaseous phase. The characteristic spectral bands were absent if discharges were
      released onto the water surface. NMR spectroscopy on the same set of samples
      independently confirmed the observation. In addition, NMR spectroscopy revealed
      overall high chemical variability that suggests strong non-linearities due to
      interdependent, sequential reaction steps.

PMID- 27896548
TI  - Four generations of SDHB-related disease: complexities in management.
AB  - SDHB mutations are linked to the familial paraganglioma syndrome type 4 (PGL4),
      which is associated with predominantly extra-adrenal disease and has high
      metastatic rates. Despite the lower penetrance rates in carriers of SDHB
      mutations compared to mutations in other paraganglioma susceptibility genes, the
      aggressive behavior of SDHB-linked disease warrants intensive surveillance to
      identify and resect tumors early. Patients with similar SDHB genotypes in whom
      the PGL syndrome manifests often exhibit very heterogeneous phenotypes. Tumors
      can arise in various locations, and management can be considerably different,
      depending on tumor site and pathology. We present a case series of five SDHB
      mutation carriers over four generations from the same family to illustrate the
      complexities in management.

PMID- 27896550
TI  - Global Trends of Monitoring and Data Collection on the HIV Response among Key
      Populations Since the 2001 UN Declaration of Commitment on HIV/AIDS.
AB  - Monitoring and evaluation indicators for HIV programs' response to the epidemic
      among key populations (sex workers, people who inject drugs, men who have sex
      with men, transgender people) are critical for reviewing the global response.
      From the beginning of global reporting, insufficiency of data has been a
      challenge for monitoring the epidemic response among key populations. However,
      key populations were only indirectly referenced in the 2001 Declaration of
      Commitment. By the 2006 Political Declaration on HIV/AIDS, data from key
      populations were still not required from every country, and were sparsely
      reported compared to other indicators. The 2011 Political Declaration on HIV/AIDS
      referenced key populations by name for the first time. In 2006, fewer than twenty
      countries (10%) reported HIV prevalence among key populations, whereas in 2012
      the number of countries surpassed sixty (30%).

PMID- 27896549
TI  - Embryonal rhabdomyosarcoma in a patient with a heterozygous frameshift variant in
      the DICER1 gene and additional manifestations of the DICER1 syndrome.
AB  - Germline mutations in the DICER1 gene are associated with an inherited cancer
      predisposition syndrome also known as the DICER1-syndrome, which is implicated in
      a broad range of tumors including pleuropulmonary blastoma, ovarian Sertoli
      Leydig cell tumors, ciliary body medulloepithelioma (CBME), pituitary blastoma,
      embryonal rhabdomyosarcoma (eRMS), anaplastic renal sarcoma as well as ocular,
      sinonasal tumors ovarian sex-cord tumors, thyroid neoplasia and cystic nephroma.
      This study describes a novel, heterozygous frameshift DICER1 mutation in a
      patient, who is affected by different tumors of the DICER1-syndrome, including
      eRMS, CBME and suspected pleuropulmonary blastoma type I. By whole-exome
      sequencing of germline material using peripheral blood-derived DNA, we identified
      a single base pair duplication within the DICER1 gene (c.3405 dupA) that leads to
      a frameshift and results in a premature stop in exon 21 (p.Gly1136Arg). The
      metachronous occurrence of two unrelated tumor entities (eRMS and CBME) in a very
      young child within a short timeframe should have raised the suspicion of an
      underlying cancer susceptibility syndrome and should be prompt tested for DICER1.

PMID- 27896551
TI  - Investing for Impact: The Global Fund Approach to Measurement of AIDS Response.
AB  - The Global Fund raises and invests nearly US$4 billion a year to support programs
      run in more than 140 countries. The Global Fund strategy 2012-2016 is focused on
      "Investing for Impact". In order to accomplish this, timely and accurate data are
      needed to inform strategies and prioritize activities to achieve greater coverage
      with quality services. Monitoring and evaluation is intrinsic to the Global
      Fund's system of performance-based funding. The Global Fund invests in
      strengthening measurement and reporting of results at all stages of the grant
      cycle. The Global Fund approach to measurement is based on three key principles
      (1) simplified reporting: the Global Fund has updated its measurement guidance to
      focus on impact, coverage and quality with the use of a harmonized set of
      indicators. (2) Supporting data systems-based on a common framework developed and
      supported by partners, it promotes investment in five common data systems:
      routine reporting including HMIS; Surveys-population based and risk group
      surveys; Analysis, reviews and transparency; Administrative and financial data
      sources; and, Vital registration systems. (3) Strengthen data use: the Global
      Fund funding encourages use of data at all levels-national, subnational and site
      level. Countries do not automatically prioritize M&E but when guidance, tools and
      investments are available, there is high level utilization of M&E systems in
      program design, planning, implementation, and results reporting. An in-depth
      analysis of the available data helps the Global Fund and countries to direct
      investments towards interventions where impact could be achieved and focus on
      target population groups and geographic areas that are most affected.

PMID- 27896552
TI  - Primary Care Physicians' Willingness to Prescribe HIV Pre-exposure Prophylaxis
      for People who Inject Drugs.
AB  - Pre-exposure prophylaxis for HIV (PrEP) is recommended for people who inject
      drugs (PWID). Despite their central role in disease prevention, willingness to
      prescribe PrEP to PWID among primary care physicians (PCPs) is largely
      understudied. We conducted an online survey (April-May 2015) of members of a
      society for academic general internists regarding PrEP. Among 250 respondents,
      74% (n = 185) of PCPs reported high willingness to prescribe PrEP to PWID. PCPs
      were more likely to report high willingness to prescribe PrEP to all other HIV
      risk groups (p's < 0.03 for all pair comparisons). Compared with PCPs delivering
      care to more HIV-infected clinic patients, PCPs delivering care to fewer HIV
      infected patients were more likely to report low willingness to prescribe PrEP to
      PWID (Odds Ratio [95% CI] = 6.38 [1.48-27.47]). PCP and practice characteristics
      were not otherwise associated with low willingness to prescribe PrEP to PWID.
      Interventions to improve PCPs' willingness to prescribe PrEP to PWID are needed.

PMID- 27896553
TI  - Associations of HIV Testing, Sexual Risk and Access to Prevention Among Female
      Sex Workers in the Dominican Republic.
AB  - The Caribbean region has one of the highest proportions of HIV in the general
      female population attributable to sex work. In 2008 (n = 1256) and 2012 (n =
      1525) in the Dominican Republic, HIV biological and behavioral surveys were
      conducted among female sex workers (FSW) in four provinces using respondent
      driven sampling. Participants were >=15 years who engaged in intercourse in
      exchange for money in the past 6 months and living/working in the study province.
      There were no statistically significant changes in HIV and other infections
      prevalence from 2008 to 2012, despite ongoing risky sexual practices. HIV testing
      and receiving results was low in all provinces. FSW in 2012 were more likely to
      receive HIV testing and results if they participated in HIV related information
      and education and had regular checkups at health centers. Further investigation
      is needed to understand barriers to HIV testing and access to prevention
      services.

PMID- 27896554
TI  - Emission of Volatile Compounds from Apple Plants Infested with Pandemis heparana
      Larvae, Antennal Response of Conspecific Adults, and Preliminary Field Trial.
AB  - This study investigated the volatile emission from apple (Malus x domestica
      Borkh., cv. Golden Delicious) foliage that was either intact, mechanically
      damaged, or exposed to larval feeding by Pandemis heparana (Denis and
      Schiffermuller) (Lepidoptera: Tortricidae). Volatiles were collected by closed
      loop-stripping-analysis and characterized by gas chromatography-mass spectrometry
      in three time periods: after 1 h and again 24 and 48 h later. Volatiles for all
      treatments also were monitored continuously over a 72-h period by the use of
      proton transfer reaction - time of flight-mass spectrometry (PTR-ToF-MS). In
      addition, the volatile samples were analyzed by gas chromatography
      electroantennographic detection (GC-EAD) using male and female antennae of P.
      heparana. Twelve compounds were detected from intact foliage compared with 23
      from mechanically-damaged, and 30 from P. heparana-infested foliage.
      Interestingly, six compounds were released only by P. heparana-infested foliage.
      The emission dynamics of many compounds measured by PTR-ToF-MS showed striking
      differences according to the timing of herbivory and the circadian cycle. For
      example, the emission of green leaf volatiles began shortly after the start of
      herbivory, and increased over time independently from the light-dark cycle.
      Conversely, the emission of terpenes and aromatic compounds showed a several-hour
      delay in response to herbivory, and followed a diurnal rhythm. Methanol was the
      only identified volatile showing a nocturnal rhythm. Consistent GC-EAD responses
      were found for sixteen compounds, including five aromatic ones. A field trial in
      Sweden demonstrated that benzyl alcohol, 2-phenylethanol, phenylacetonitrile, and
      indole lures placed in traps were not attractive to Pandemis spp. adults, but 2
      phenylethanol and phenylacetonitrile when used in combination with acetic acid
      were attractive to both sexes.

PMID- 27896555
TI  - Methyl Jasmonate-Induced Monoterpenes in Scots Pine and Norway Spruce Tissues
      Affect Pine Weevil Orientation.
AB  - In large parts of Europe, insecticide-free measures for protecting conifer plants
      are desired to suppress damage by the pine weevil Hylobius abietis (L.).
      Treatment with methyl jasmonate (MeJA), a chemical elicitor already used in crop
      production, may enhance expression of chemical defenses in seedlings in conifer
      regenerations. However, in a previous experiment, MeJA treatment resulted in
      substantially better field protection for Scots pine (Pinus sylvestris L.) than
      for Norway spruce (Picea abies (L.) Karst.). Hypothesizing that the variations
      may be at least due partly to volatiles released by MeJA-treated seedlings and
      their effects on pine weevil orientation, we examined tissue extracts of
      seedlings (from the same batches as previously used) by two-dimensional GC-MS. We
      found that the MeJA treatment increased contents of the monoterpene (-)-beta
      pinene in phloem (the weevil's main target tissue) of both tree species, however,
      the (-)-beta-pinene/(-)-alpha-pinene ratio increased more in the phloem of P.
      sylvestris. We also tested the attractiveness of individual monoterpenes found in
      conifer tissues (needles and phloem) for pine weevils using an arena with traps
      baited with single-substance dispensers and pine twigs. Trap catches were reduced
      when the pine material was combined with a dispenser releasing (-)-beta-pinene,
      (+)-3-carene, (-)-bornyl acetate or 1,8-cineole. However, (-)-alpha-pinene did
      not have this effect. Thus, the greater field protection of MeJA-treated P.
      sylvestris seedlings may be due to the selective induction of increases in
      contents of the deterrent (-)-beta-pinene, in contrast to strong increases in
      both non-deterrent (-)-alpha-pinene and the deterrent (-)-beta-pinene in P. abies
      seedlings.

PMID- 27896556
TI  - Towards standardized automated immunomonitoring: an automated ELISpot assay for
      safe and parallelized functionality analysis of immune cells.
AB  - The ELISpot assay is used for the detection of T cell responses in clinical
      trials and vaccine evaluations. Standardization and reproducibility are necessary
      to compare the results worldwide, inter- and intra-assay variability being
      critical factors. To assure operator safety as well as high-quality experiment
      performance, the ELISpot assay was implemented on an automated liquid handling
      platform, a Tecan Freedom EVO. After validation of the liquid handling, automated
      loading of plates with cells and reagents was investigated. With step by step
      implementation of the manual procedure and liquid dispensing optimization on the
      robot platform, a fully automated ELISpot assay was accomplished with plates
      remaining in the system from the plate blocking step to spot development. The
      mean delta difference amounted to a maximum of 6%, and the mean dispersion was
      smaller than in the manual assay. Taken together, we achieved with this system
      not only a lower personnel attendance but also higher throughput and a more
      precise and parallelized analysis. This platform has the potential to guarantee
      validated, safe, fast, reproducible and cost-efficient immunological and
      toxicological assays in the future.

PMID- 27896557
TI  - Cytotoxic and apoptotic activities of extract of Amaranthus spinosus L. in Allium
      cepa and human erythrocytes.
AB  - The present study examined the apoptosis inducing effects of Amaranthus spinosus
      L. aqueous extract in Allium cepa root meristematic cells and human erythrocytes.
      Cytogenetic assay revealed many apoptosis inducing cytogenetic aberrations viz.,
      cytoplasmic breakage, cytoplasmic disintegration, cytoplasmic shrinkage, receding
      of cytoplasm, cytoplasmic vacuolation, enucleated cell, ghost cell, nuclear
      vacuolation, nuclear fragmentation and nuclear disintegration. A remarkable
      modification of red blood cell surface morphology was observed in the result of
      RBC assay. The treated RBCs show membrane blebbing and shrinkage, features
      typical for apoptosis in nucleated cells. Significant induction of cell death was
      observed in treated Allium root tip cells after Evans blue staining, disclosing
      the membrane damage potential of the plant extract. TTC assay results in reduced
      mitochondrial/metabolic activity in Allium root tip cells after treatment,
      designating the adverse effect of plant extract on mitochondrial respiratory
      chain. These results confirm the apoptosis inducing potential of A. spinosus
      extract. Confirming the present results by further in vitro studies, it can be
      effectively targeted against cell proliferation during cancer treatment by
      inducing apoptosis. Thus from the present investigation it can be concluded that
      the aqueous extract of A. spinosus exhibited apoptosis induction and cytotoxic
      activities.

PMID- 27896558
TI  - H3K9ac involved in the decondensation of spermatozoal nuclei during
      spermatogenesis in Chinese mitten crab Eriocheir sinensis.
AB  - As a well-known crustacean model species, the Chinese mitten crab Eriocheir
      sinensis presents spermatozoa with decondensed DNA. Our aim was to analyze
      structural distribution of the histone H3 and its acetylated lysine 9 (H3K9ac)
      during spermatogenesis for the mechanistic understanding of the nuclear
      decondensation of the spermatozoa in E. sinensis. Using specific antibodies, we
      followed the structural distribution and acetylated lysine 9 of the histone H3
      during spermatogenesis, especially spermiogenesis, of E. sinensis. Various
      spermary samples at different developmental stages were used for histological
      immunofluorescence and ultrastructural immunocytochemistry. Our results
      demonstrate a wide distribution of the histone H3 and H3K9ac during
      spermatogenesis, including spermatogonia, spermatocytes, spermatids, and immature
      and mature spermatozoa except for absence of H3K9ac in the secondary
      spermatocytes. Especially during the initial stage of nuclear decondensation,
      histone H3 lysine 9 was acetylated and then an amount of H3K9ac was removed from
      within to outside of the nuclei of late spermatids. The portion of remaining
      H3K9ac was gradually transferred from the nuclei during the stages of spermatozoa
      maturation. Our findings suggest both the acetylation of histone H3 lysine 9 and
      the remain of H3K9ac to contribute to the nuclear decondensation in spermatozoa
      of E. sinensis.

PMID- 27896559
TI  - Antiviral activity of hemolymph of Podalia against rubella virus.
AB  - Many active principles produced by animals, plants and microorganisms have been
      employed in the development of new drugs for the treatment of human diseases.
      Among animals known to produce pharmacologically active molecules that interfere
      in human cell physiology. Rubella virus (genus Rubivirus, family Togaviridae) is
      a single stranded RNA virus of positive genome polarity. Rubella virus infection
      of susceptible women during the first trimester of pregnancy often results in
      long-term virus persistence in the fetus causing multiple organ abnormalities.
      Potent antiviral activity against rubella virus (RV) has been observed in the
      hemolymph of Podalia sp. (Lepidoptera: Megalopygidae). This study evaluated the
      effect of hemolymph on RV infected Statens Serum Institute Rabbit Cornea (SIRC)
      cells. Results of cell viability and cell proliferation assays indicated that
      hemolymph was not toxic to cultured SIRC cells. Viral binding assay, antiviral
      assay, PCR, real-time PCR, and transmission electron microscopy were used to
      demonstrate that hemolymph in post-treatment could inhibit the production of
      infectious RV particles. Specifically, hemolymph was found to inhibit RV
      adsorption to the SIRC cells.

PMID- 27896560
TI  - Neuroimaging findings of Zika virus infection: beyond the brain CT scans.

PMID- 27896561
TI  - Polyester Fabric's Fluorescent Dyeing in Supercritical Carbon Dioxide and its
      Fluorescence Imaging.
AB  - As one of the most important coumarin-like dyes, disperse fluorescent Yellow 82
      exhibits exceptionally large two-photon effects. Here, it was firstly introduced
      into the supercritical CO2 dyeing polyester fabrics in this work. Results of the
      present work showed that the dyeing parameters such as the dyeing time, pressure
      and temperature had remarkable influences on the color strength of fabrics. The
      optimized dyeing condition in supercritical CO2 dyeing has been proposed that the
      dyeing time was 60 min; the pressure was 25 MPa and the temperature was 120 
      degrees C. As a result, acceptable products were obtained with the wash and rub
      fastness rating at 5 or 4-5. The polyester fabrics dyed with fluorescent dyes can
      be satisfied for the requirement of manufacturing warning clothing. Importantly,
      the confocal microscopy imaging technology was successfully introduced into
      textile fields to observe the distribution and fluorescence intensity of disperse
      fluorescent Yellow 82 on polyester fabrics. As far as we know, this is the first
      report about supercritical CO2 dyeing polyester fabrics based on disperse
      fluorescent dyes. It will be very helpful for the further design of new
      fluorescent functional dyes suitable for supercritical CO2 dyeing technique.

PMID- 27896562
TI  - Characterization of isolates of equine infectious anemia virus in Brazil.
AB  - Equine infectious anemia is an important infectious disease that affects equids
      worldwide. Control of the disease is currently based on detection of anti-p26
      EIAV by Agar Gel Immunodiffusion (AGID). In this work, 62 animals were examined
      by AGID and nested-PCR using primers for the gag gene. Fifty-three samples
      (85.5%) were positive by nested-PCR, whereas only 33 samples (53%) were positive
      for AGID. Fifteen amplicons obtained by nested-PCR were sequenced and the aligned
      results subjected to phylogenetic analysis. The analysis suggests that the
      Brazilian EIAV form a cluster with WSU5, EIAVUK and Wyoming strains from United
      States.

PMID- 27896563
TI  - Broad-spectrum antiviral properties of andrographolide.
AB  - Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It
      can be isolated from various plants of the genus Andrographis, commonly known as
      'creat'. This purified compound has been tested for its anti-inflammatory effects
      in various stressful conditions, such as ischemia, pyrogenesis, arthritis,
      hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti
      inflammatory effects, andrographolide also exhibits immunomodulatory effects by
      effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis,
      and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of
      andrographolide form the foundation for the use of this miraculous compound to
      restrain virus replication and virus-induced pathogenesis. The present article
      covers antiviral properties of andrographolide in variety of viral infections,
      with the hope of developing of a new highly potent antiviral drug with multiple
      effects.

PMID- 27896564
TI  - Children's Gender-Typed Toy Interests: Does Propulsion Matter?
AB  - Children's toy play is at the foundation of child development. However, gender
      differentiation in early play experiences may result in gender differences in
      cognitive abilities, social interactions, and vocational choices. We investigated
      gender-typing of toys and toys' propulsive properties (e.g., wheels, forward
      motion) as possible factors impacting children's toy interests, perceptions of
      other children's interests, and children's actual toy choices during free play.
      In Studies 1 and 2, 82 preschool children (42 boys, 40 girls; mean age = 4.90
      years) were asked to report their interest and perceptions of other children's
      interests in toys. In Study 1, masculine, feminine, and neutral toys with and
      without propulsive properties were presented. Children reported greater interest
      in gender-typed toys and neutral toys compared to cross-gender-typed toys. In
      Study 2, unfamiliar, neutral toys with and without propulsive properties were
      presented. Propulsive properties did not affect children's interest across both
      studies. Study 3 was an observational study that assessed toy preferences among
      42 preschool children (21 males, 21 females, mean age = 4.49 years) during a play
      session with masculine, feminine, and neutral toys with and without propulsive
      properties. Gender-typed toy preferences were less apparent than expected, with
      children showing high interest in neutral toys, and girls playing with a wide
      variety of masculine, feminine, and neutral toys. Gender differences in interest
      for toys with propulsion properties were not evident. Overall, gender differences
      in children's interest in toys as a function of propulsion properties were not
      found in the three experiments within this study.

PMID- 27896565
TI  - None of the Above: Toward Identity and Community-Based Understandings of
      (A)sexualities.

PMID- 27896566
TI  - Croatia Needs a Gender Incongruence Diagnosis for Prepubertal Children.

PMID- 27896568
TI  - How Can a Good Idea Fail? Basal Insulin Peglispro [LY2605541] for the Treatment
      of Type 2 Diabetes.
AB  - INTRODUCTION: Lack of control in diabetic patients has stimulated the development
      of new insulin analogues. One of these was basal insulin peglispro (BIL) or
      LY2605541; it had a large hydrodynamic size, flat pharmacokinetic profile, half
      life of 2-3 days and acted preferably in the liver. METHODS: We reviewed the
      recent literature examining the pharmacokinetics, pharmacodynamics, efficacy and
      safety of BIL treatment in type 2 diabetes patients. RESULTS: The pharmacodynamic
      and pharmacokinetic outline of BIL seemed to have an advantage over neutral
      protamine Hagedorn and glargine insulins. Recently, phase 3 studies suggested BIL
      was superior to glargine in reducing glucose levels in type 1 and type 2 diabetes
      patients in addition to causing less weight gain. It showed a different
      hypoglycaemia rate profile depending on the study population, with less nocturnal
      hypoglycaemia compared to glargine. Unfortunately, it caused higher transaminase
      and triglyceride levels, which led the company to discontinue development. The
      decision came after it had been analysed by the regulatory authorities and other
      external experts concerning the worse liver profile data from the IMAGINE trials.
      CONCLUSIONS: BIL was an adequate basal insulin analogue with interesting specific
      properties. Unfortunately the disadvantages as shown in the lipid values and
      liver function tests led to its failure.

PMID- 27896567
TI  - FOXO1 and LXRalpha downregulate the apolipoprotein A-I gene expression during
      hydrogen peroxide-induced oxidative stress in HepG2 cells.
AB  - Reactive oxygen species damage various cell components including DNA, proteins,
      and lipids, and these impairments could be a reason for severe human diseases
      including atherosclerosis. Forkhead box O1 (FOXO1), an important metabolic
      transcription factor, upregulates antioxidant and proapoptotic genes during
      oxidative stress. Apolipoprotein A-I (ApoA-I) forms high density lipoprotein
      (HDL) particles that are responsible for cholesterol transfer from peripheral
      tissues to liver for removal in bile in vertebrates. The main sources for plasma
      ApoA-I in mammals are liver and jejunum. Hepatic apoA-I transcription depends on
      a multitude of metabolic transcription factors. We demonstrate that ApoA-I
      synthesis and secretion are decreased during H2O2-induced oxidative stress in
      human hepatoma cell line HepG2. Here, we first show that FOXO1 binds to site B of
      apoA-I hepatic enhancer and downregulates apoA-I gene activity in HepG2 cells.
      Moreover, FOXO1 and LXRalpha transcription factors participate in H2O2-triggered
      downregulation of apoA-I gene together with Src, JNK, p38, and AMPK kinase
      cascades. Mutations of sites B or C as well as the administration of siRNAs
      against FOXO1 or LXRalpha to HepG2 cells abolished the hydrogen peroxide-mediated
      suppression of apoA-I gene.

PMID- 27896570
TI  - Quiet MR sequences in clinical routine: initial experience in abdominal imaging.
AB  - OBJECTIVE: Purpose of our study was to demonstrate the feasibility and
      limitations of acoustic noise reduction in a standard clinical MRI protocol for
      abdominal imaging. METHODS: Acoustic noise and image quality were assessed in 17
      patients for a standard liver imaging protocol including TSE and GRE sequences
      and compared to quiet optimizations as described by Heismann et al. Two blinded
      readers scored artifacts, the delineation of the abdominal organs and level of
      diagnostic confidence. Means of the sound level measurements, the ratings and the
      measurement of SNR and CNR were compared. RESULTS: Significant reduction of
      acoustic noise was measured for T2 TSE (-30.7%), T2 HASTE (-22.6%) and less
      difference for T1 DIXON (-4.7%) and T1 FLASH (-2.7%). SNR and CNR were lower for
      quiet T2 TSE (-18.0%, -23.1%) and T2 HASTE (-46.2%, -37.7%) and higher for T1
      DIXON (+32.0%, +24.4%). Inter-rater correlation was k = 0.987 with p < 0.001.
      CONCLUSIONS: Although sequence-based noise optimizations faces problems in T1
      FLASH and DIXON sequences, there is an important acoustic benefit in T2 TSE and
      T2 HASTE sequences, which goes along with a maintained image quality and
      diagnostic confidence.

PMID- 27896569
TI  - Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis.
AB  - PURPOSE: IgG4-related disease is a systemic inflammatory disease characterized by
      infiltration of IgG4-positive plasma cells into multiple organs, including the
      pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of
      IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is
      difficult because its clinical features, such as pituitary swelling and
      hypopituitarism, are similar to those of other pituitary diseases, including
      lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and
      significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear. METHODS:
      In this case-control study, we used single indirect immunofluorescence on human
      pituitary substrates to assess the prevalence of serum APA in 17 patients with
      IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic
      infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9
      healthy subjects. We further analyzed the endocrine cells targeted by the
      antibodies using double indirect immunofluorescence. RESULTS: APA were found in 5
      of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or
      healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH
      cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass,
      rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved
      in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of
      the cases. CONCLUSIONS: Our study suggests that autoimmunity is involved in the
      pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target,
      highlighting a possible new diagnostic marker for this condition.

PMID- 27896571
TI  - Erratum to: Japanese phase II study of rituximab maintenance for untreated
      indolent B-cell non-Hodgkin lymphoma with high tumor burden.

PMID- 27896572
TI  - Identification of novel mutations in HFE, HFE2, TfR2, and SLC40A1 genes in
      Chinese patients affected by hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HH) is a group of inherited iron-overload disorders
      associated with pathogenic defects in the genes encoding hemochromatosis (HFE),
      hemojuvelin (HJV/HFE2), hepcidin (HAMP), transferrin receptor 2 (TfR2), and
      ferroportin (FPN1/SLC40A1) proteins, and the clinical features are well
      described. However, there have been only a few detailed reports of HH in Chinese
      populations. Thus, there is insufficient patient information for population-based
      analyses in Chinese populations or comparative studies among different ethical
      groups. In the current work, we describe eight Chinese cases of hereditary
      hemochromatosis. Gene sequencing results revealed eight mutations (five novel
      mutations) in HFE, HFE2, TfR2, and SLC40A1 genes in these Chinese HH patients. In
      addition, we used Polymorphism Phenotyping v2 (Polyphen), Sorting Intolerant From
      Tolerant (SIFT), and a sequence alignment program to predict the molecular
      consequences of missense mutations.

PMID- 27896575
TI  - Retraction Note to: The Efficacy of Epidermal Growth Factor Receptor Tyrosine
      Kinase Inhibitors for Molecularly Selected Patients with Non-Small Cell Lung
      Cancer: A Meta-Analysis of 30 Randomized Controlled Trials.

PMID- 27896573
TI  - Greater decline in memory and global neurocognitive function in HIV/hepatitis C
      co-infected than in hepatitis C mono-infected patients treated with pegylated
      interferon and ribavirin.
AB  - The human immunodeficiency virus (HIV), hepatitis C virus (HCV), and the
      treatment of HCV with pegylated interferon and ribavirin (IFN/RBV) have been
      associated with neurocognitive and psychiatric abnormalities. The goal of this
      research was to prospectively evaluate neurocognitive functioning among a group
      of HCV mono-infected and HIV/HCV co-infected patients during the first 24 weeks
      of IFN/RBV treatment while accounting for practice effects, normal variations in
      change over time, and variations in IFN/RBV treatment exposure. Forty-four HCV
      mono-infected and 30 HIV/HCV co-infected patients were enrolled in a prospective
      study of patients beginning on IFN/RBV for chronic HCV infection. Patients were
      administered a depression inventory, a measure of fatigue, a structured
      psychiatric interview, and a neurocognitive battery at baseline and 24 weeks
      after initiation of treatment. Analyses were conducted to explore possible
      associations between neurocognitive functioning and the following: HIV/HCV co
      infection vs. HCV mono-infection, IFN and RBV treatment exposure, psychiatric
      status, liver disease stage, and other medical characteristics. At baseline,
      there were no significant differences between the two groups' neuropsychiatric or
      neurocognitive function other than the mono-infected group had significantly
      higher reports of fatigue (p = 0.033). Over the course of 24 weeks of treatment
      after controlling for practice effects, the HIV/HCV co-infected patients
      experienced significantly greater declines in memory (t(56) = 2.14, p = 0.037)
      and global neurocognitive functioning (t(53) = 2.28, p = 0.027). In a well
      characterized sample of mono-infected and co-infected patients, it appears that
      persons with HIV/HCV co-infection are potentially more vulnerable to
      neurocognitive sequalae during HCV treatment.

PMID- 27896574
TI  - Cognitive function in early HIV infection.
AB  - This study aimed to examine cognitive function in acute/early HIV infection over
      the subsequent 2 years. Fifty-six HIV+ subjects and 21 seronegative participants
      of the Chicago Early HIV Infection Study were evaluated using a comprehensive
      neuropsychological assessment at study enrollment and at 2-year follow-up.
      Cognitive performance measures were compared in the groups using t tests and
      mixed-effect models. Patterns of relationship with clinical measures were
      determined between cognitive function and clinical status markers using
      Spearman's correlations. At the initial timepoint, the HIV group demonstrated
      significantly weaker performance on measures of verbal memory, visual memory,
      psychomotor speed, motor speed, and executive function. A similar pattern was
      found when cognitive function was examined at follow-up and across both
      timepoints. The HIV subjects had generally weaker performance on psychomotor
      speed, executive function, motor speed, visual memory, and verbal memory. The
      rate of decline in cognitive function across the 2-year follow-up period did not
      differ between groups. Correlations between clinical status markers and cognitive
      function at both timepoints showed weaker performance associated with increased
      disease burden. Neurocognitive difficulty in chronic HIV infection may have very
      early onset and reflect consequences of initial brain viral invasion and
      neuroinflammation during the intense, uncontrolled viremia of acute HIV
      infection. Further characterization of the changes occurring in initial stages of
      infection and the risk and protective factors for cognitive function could inform
      new strategies for neuroprotection.

PMID- 27896577
TI  - Modified laparoscopic simple enucleation with single-layer suture technique
      versus standard laparoscopic partial nephrectomy for treating localized renal
      cell carcinoma.
AB  - OBJECTIVES: To compare modified laparoscopic simple enucleation (MLSE) and
      standard laparoscopic partial nephrectomy (SLPN) for treating localized renal
      cell carcinoma in our large institutional experience. METHODS: We evaluated 385
      consecutive patients who underwent MLSE or SLPN for renal tumors in our
      institution from January 2013 to December 2015 in terms of perioperative
      pathological and oncologic outcome variables. During MLSE, the single-layer
      suture technique was performed for renal reconstruction. RESULTS: In total, 280
      patients underwent MLSE and 105 underwent SLPN. Mean operative time was 182.1 and
      192.8 min, respectively (p = 0.078). Warm ischemic time was significantly lower
      in the MLSE than SLPN group (23.2 vs 25.4 min; p = 0.004). The estimated blood
      loss was similar (p = 0.537). Tumor bed suturing was performed in 9.3 and 82.9%
      of MLSE and SLPN cases (p = 0.000). No hilar clamping was needed for 29 MLSE
      patients (10.4%) and 4 SLPN patients (3.8%) (p = 0.041). Grade III complications
      were reported in 5 (1.8%) MLSE patients and 7 (6.6%) SLPN patients (p = 0.034).
      The incidence of positive surgical margins was comparable between the MLSE and
      SLPN groups (1.8 and 5.7%, p = 0.086). After a median follow-up of 18 months,
      recurrence did not differ between the 2 groups: 9 (3.2%) MLSE patients and 4
      (3.8%) SLPN patients (p = 1.000). CONCLUSIONS: MLSE may confer shorter warm
      ischemic time, almost no need for tumor bed suturing and less grade III
      complications than SLPN, with similar oncologic outcomes. MLSE may be safe and
      acceptable for patients undergoing partial nephrectomy.

PMID- 27896576
TI  - Comparing the bulking effect of calcium hydroxyapatite and Deflux injection into
      the bladder neck for improvement of urinary incontinence in bladder exstrophy
      epispadias complex.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of the endoscopic
      injection of calcium hydroxyapatite (CaHA) into the bladder neck (BN) region of
      patients with urinary incontinence and bladder exstrophy-epispadias complex
      (BEEC). PATIENTS AND METHODS: We designed a retrospective cohort study in which
      we retrospectively studied medical charts of female and male patients of BEEC who
      had undergone CaHA or Deflux injection for continence improvement between 2009
      and 2014. Sixteen incontinent patients with a mean +/- SD age of 8.09 +/- 3.5
      years received an endoscopic submucosal injection of 5.4 ml of pure CaHA powder
      with autologous plasma (group A). Patients in group B (N = 21), control group,
      with a mean +/- SD age of 7.51 +/- 2.8 years received Deflux injection (5.1 ml).
      The mean follow-up after injection was 38 +/- 5.2 and 33 +/- 4.1 months in groups
      A and B, respectively. RESULTS: No post-injection complication was detected in
      none of the patients during the follow-up. Eleven patients (68.75%) in group A
      became socially dry following 1-2 injections, the degree of incontinence was
      improved in 4 patients (25%), and there was no change in one patient (6.25%).
      However, Deflux injection resulted in complete dryness in 14 (66.66%),
      improvement in the degree of incontinence in 5 (23.81%) and no change in 2
      patients (9.52%), leading to no significant difference in continence achievement
      between CaHA and Deflux groups (p = 0.9). The statistical analysis was not
      significantly different in terms of bladder capacity (p = 0.7) or Q max (p =
      0.8). CONCLUSION: The preliminary results of this study revealed that CaHA may be
      applied as an affordable bulking agent in treatment of urinary incontinence in
      BEEC.

PMID- 27896579
TI  - Prostatic artery embolization in treating benign prostatic hyperplasia: a
      systematic review.
AB  - INTRODUCTION: We systemically reviewed the current evidence on prostatic artery
      embolization (PAE) in treating men with benign prostatic hyperplasia. METHODS: A
      systemic literature search was conducted in PubMed, EMBASE and Web of Science on
      1 May 2016 without time constraints. Outcomes of interest included the changes in
      the International Prostate Symptom Score (IPSS), quality-of-life (QOL) score,
      peak urinary flow (Qmax), post-void residual urine (PVR), International Index of
      Erectile Function (IIEF) score, prostate volume (PV) and prostate-specific
      antigen (PSA) level. RESULTS: A total of 987 records were identified through
      database searching. After removing duplicates, screening and reviewing full
      length texts, a total of five records remained, with two randomized controlled
      trials and three non-randomized cohort studies. Transurethral resection of
      prostate resulted in better IPSS than PAE. Open prostatectomy had better IPSS,
      QOL score, Qmax and PVR, but worse IIEF score than PAE at 1 year. Unilateral PAE
      had higher rate of poor clinical outcome than bilateral PAE, but the difference
      became statistically insignificant after adjusting for age; IPSS, QOL score,
      Qmax, PVR, IIEF score, PV and PSA did not differ between the two groups. PAE with
      100 MUm PVA particles resulted in greater reduction in PSA level, but worse IIEF
      score than PAE with 200 MUm PVA particles; IPSS, QOL score, Qmax, PVR, PV and
      poor clinical outcome did not differ between the two groups. CONCLUSION: Evidence
      on different aspects of PAE was limited. Further studies are warranted to
      investigate the role of PAE as compared to other forms of medical and surgical
      treatment.

PMID- 27896578
TI  - Is there evidence for a close connection between side of intravesical tumor
      location and ipsilateral lymphatic spread in lymph node-positive bladder cancer
      patients at radical cystectomy? Results of the PROMETRICS 2011 database.
AB  - PURPOSE: To evaluate the possible association between bladder tumor location and
      the laterality of positive lymph nodes (LN) in a prospectively collected multi
      institutional radical cystectomy (RC) series. METHODS: The study population
      included 148 node-positive bladder cancer (BC) patients undergoing RC and pelvic
      lymph node dissection in 2011 without neoadjuvant chemotherapy and without
      distant metastasis. Tumor location was classified as right, left or bilateral and
      compared to the laterality of positive pelvic LN. A logistic regression model was
      used to identify predictors of ipsilaterality of lymphatic spread. Using
      multivariate Cox regression analyses (median follow-up: 25 months), the effect of
      the laterality of positive LN on cancer-specific mortality (CSM) was estimated.
      RESULTS: Overall, median 18.5 LN [interquartile range (IQR), 11-27] were removed
      and 3 LN (IQR 1-5) were positive. There was concordance of tumor location and
      laterality of positive LN in 82% [95% confidence interval (CI), 76-89]. Patients
      with unilateral tumors (n = 78) harbored exclusively ipsilateral positive LN in
      67% (95% CI 56-77). No criteria were found to predict ipsilateral positive LN in
      patients with unilateral tumors. CSM after 3 years in patients with ipsilateral,
      contralateral, and bilateral LN metastasis was 41, 67, and 100%, respectively (p
      = 0.042). However, no significant effect of the laterality of positive pelvic LN
      on CSM could be confirmed in multivariate analyses. CONCLUSIONS: Our prospective
      cohort showed a concordance of tumor location and laterality of LN metastasis in
      BC at RC without any predictive criteria and without any influence on CSM. It is
      debatable, whether these findings may contribute to a more individualized patient
      management.

PMID- 27896580
TI  - Highly improved acarbose production of Actinomyces through the combination of
      ARTP and penicillin susceptible mutant screening.
AB  - Atmospheric and room temperature plasma (ARTP) was first employed to generate
      mutants of Actinomyces JN537 for improving acarbose production. To obtain higher
      acarbose producing strains, the method of screening the strains for
      susceptibility to penicillin was used after treatment with ARTP. The rationale
      for the strategy was that mutants showing penicillin susceptibility were likely
      to be high acarbose producers, as their ability to synthesize cell walls was weak
      which might enhance metabolic flux to the pathway of acarbose biosynthesis.
      Acarbose yield of the mutant strain M37 increased by 62.5 % than that of the
      original strain. The contents of monosaccharides and amino acids of the cell wall
      of M37 were lower than that of the original strain. The acarbose production
      ability in mutant strain remained relatively stable after 10 generations. This
      work provides a promising strategy for obtaining high acarbose-yield strains by
      combination of ARTP mutation method and efficient screening technique.

PMID- 27896582
TI  - Effect of irrigation on soil health: a case study of the Ikere irrigation project
      in Oyo State, southwest Nigeria.
AB  - Irrigated agriculture is one of the significant contributors to the food security
      of the millennium development goals (MDGs); however, the modification of soil
      matrix by irrigation could alter the overall soil health due to changes in soil
      properties and processes. The objective of the study was to evaluate the effect
      of irrigation on soil quality status of the Ikere center pivot irrigation project
      site in Oyo State, southwest Nigeria. Disturbed soil samples were collected from
      0 to 30, 30 to 60, and 60 to 90-cm layers from four different sites in three
      replicates, within the project location for the determination of soil bio
      chemical properties. The average values of sodium adsorption ratio (SAR) < 13,
      electrical conductivity (EC) <4 MUS/cm, and pH < 8.5 showed that the soil
      condition is normal in relation to salinity and sodicity hazards. The effective
      cation exchange capacity (ECEC), soil organic matter (SOM), total nitrogen (TN),
      and calcium ion (Ca2+) concentrations were low while the available phosphorus (P)
      was moderate. The principal component analysis showed EC, ECEC, SAR, SOM, and TN
      as the minimum data set (MDS) for monitoring and assessing the soil quality
      status of this irrigation field. In terms of bio-chemical properties, the soil
      quality index (SQI) of the field was average (about 0.543) while the sampling
      locations were ranked as site 2 > site 4 > site 3 > site 1 in terms of SQI. The
      results of this study are designated as baseline for future evaluation of soil
      quality status of this irrigation field and further studies should incorporate
      soil physical and more biological properties when considering overall soil
      quality status.

PMID- 27896583
TI  - Use of ultra-high spatial resolution aerial imagery in the estimation of
      chaparral wildfire fuel loads.
AB  - Development of methods that more accurately estimate spatial distributions of
      fuel loads in shrublands allows for improved understanding of ecological
      processes such as wildfire behavior and postburn recovery. The goal of this study
      is to develop and test remote sensing methods to upscale field estimates of
      shrubland fuel to broader-scale biomass estimates using ultra-high spatial
      resolution imagery captured by a light-sport aircraft. The study is conducted on
      chaparral shrublands located in eastern San Diego County, CA, USA. We measured
      the fuel load in the field using a regression relationship between basal area and
      aboveground biomass of shrubs and estimated ground areal coverage of individual
      shrub species by using ultra-high spatial resolution imagery and image processing
      routines. Study results show a strong relationship between image-derived shrub
      coverage and field-measured fuel loads in three even-age stands that have regrown
      approximately 7, 28, and 68 years since last wildfire. We conducted ordinary
      least square analysis using ground coverage as the independent variable regressed
      against biomass. The analysis yielded R 2 values ranging from 0.80 to 0.96 in the
      older stands for the live shrub species, while R 2 values for species in the
      younger stands ranged from 0.32 to 0.89. Pooling species-based data into larger
      sample sizes consisting of a functional group and all-shrub classes while
      obtaining suitable linear regression models supports the potential for these
      methods to be used for upscaling fuel estimates to broader areal extents, without
      having to classify and map shrubland vegetation at the species level.

PMID- 27896581
TI  - Secondary metabolites of endophytic Xylaria species with potential applications
      in medicine and agriculture.
AB  - Fungal endophytes are important sources of bioactive secondary metabolites. The
      genus Xylaria Hill (ex Schrank, 1789, Xylariaceae) comprises various endophytic
      species associated to both vascular and non vascular plants. The secondary
      metabolites produced by Xylaria species include a variety of volatile and non
      volatile compounds. Examples of the former are sesquiterpenoids, esters, and
      alcohols, among others; and of the latter we find terpenoids, cytochalasins,
      mellein, alkaloids, polyketides, and aromatic compounds. Some of these
      metabolites have shown potential activity as herbicides, fungicides, and
      insecticides; others possess antibacterial, antimalarial, and antifungal
      activities, or alpha-glucosidase inhibitory activity. Thus metabolites from
      Xylaria are promising compounds for applications in agriculture for plague
      control as biopesticides, and biocontrol agents; and in medicine, for example as
      drugs for the treatment of infectious and non-infectious diseases. This review
      seeks to show the great value of the secondary metabolites of Xylaria,
      particularly in the agriculture and medicine fields.

PMID- 27896585
TI  - Effect of an herbal mixture of Cinnamon Cortex, Persicae Semen, and Natril Sulfas
      on collagen-induced arthritis and lipopolysaccharides-induced nuclear factor
      kappa B signaling.
AB  - OBJECTIVE: To investigate the anti-arthritic and anti-inflammatory effects of the
      mixture of three herbal agents, Cinnamon Cortex, Persica Semen, and Natril Sulfas
      (CPN), the major ingredients of Taoren Chengqi Decoction (). METHODS: Collagen
      induced arthritis (CIA) was induced by immunization with bovine type II collagen
      on day 1 and 21. DBA/1J mice were orally administered the water extract of CPN
      (100 and 500 mg/kg) and indomethacin (1 mg/kg) or vehicle (water) 3 times per
      week for 6 weeks. Arthritic symptoms were recorded on day 29, 31, 33, 36 and 38.
      On sacrififi ce, serum was obtained for inflammatory markers and anti-collagen
      antibodies as well as arthritic joints were obtained for histologic analysis. For
      the evaluation of in vitro anti-inflammatory mechanism of CPN, peritoneal
      macrophages were isolated from thioglycollate injected C57BL/6 mice and
      stimulated with lipopolysaccharides (LPS) for 15 min in the presence of CPN
      extract. Levels of inhibitor of NF-kappaB alpha isoform (IkappaBalpha), phospho
      p38, phospho-C-Jun N-terminal kinases (JNK) and phospho-extracellular signal
      regulated kinase 1/2 (ERK1/2) were detected by Western blot. RESULTS: Compared
      with mice in CIA group, oral administration of CPN signififi cantly reduced the
      clinical scores (P<0.05), histological analysis revealed the protective effect of
      CPN on inflamed joints. Serum levels of the pro-inflammatory markers tumor
      necrosis factor-alpha, interleukin-6 and prostaglandin E2, but not anti-collagen
      antibodies, were significantly reduced (P<0.05). CPN did not affect the
      activation of p38, JNK and ERK1/2 but inhibited LPS-induced IkappaBalpha
      degradation, a required event prior to the translocation of NF-kappaB to the
      nucleus. CONCLUSIONS: The ameliorating effect of CPN on arthritis progression
      seems to be mediated by its anti-inflammatory effect, without affecting antibody
      response. As a supplementary agent, CPN could be benefifi cial for treatment of
      CIA.

PMID- 27896584
TI  - Soil contamination assessment for Pb, Zn and Cd in a slag disposal area using the
      integration of geochemical and microbiological data.
AB  - Improper disposal of mining waste is still considered a global problem, and
      further details on the contamination by potentially toxic metals are required for
      a proper assessment. In this context, it is important to have a combined view of
      the chemical and biological changes in the mining dump area. Thus, the objective
      of this study was to evaluate the Pb, Zn and Cd contamination in a slag disposal
      area using the integration of geochemical and microbiological data. Analyses of
      soil organic matter (SOM), pH, Eh, pseudo-total concentration of metals,
      sequential extraction and microbial community by polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE) were conducted. Metal
      availability was evaluated based on the geoaccumulation index (I geo), ecological
      risk ([Formula: see text]), Risk Assessment Code (RAC) and experimental data, and
      different reference values were tested to assist in the interpretation of the
      indices. The soil pH was slightly acidic to neutral, the Eh values indicated
      oxidized conditions and the average SOM content varied from 12.10 to 53.60 g kg
      1. The average pseudo-total concentrations of metals were in the order of Zn > Pb
      > Cd. Pb and Zn were mainly bound to the residual fraction and Fe-Mn oxides, and
      a significant proportion of Cd was bound to the exchangeable and carbonate
      fractions. The topsoil (0-20 cm) is highly contaminated (I geo) with Cd and has a
      very high potential ecological risk ([Formula: see text]). Higher bacterial
      diversity was mainly associated with higher metal concentrations. It is concluded
      that the integration of geochemical and microbiological data can provide an
      appropriate evaluation of mining waste-contaminated areas.

PMID- 27896586
TI  - Effect of berberine on the ratio of high-molecular weight adiponectin to total
      adiponectin and adiponectin receptors expressions in high-fat diet fed rats.
AB  - OBJECTIVE: To assess the effects of berberine (BBR) on high-molecular weight
      (HMW) adiponectin and adiponectin receptors (adipoR1/adipoR2) expressions in high
      fat (HF) diet fed rats. METHODS: Forty Wistar male rats were randomly assigned
      into a normal diet fed group and three HF diet (fat for 45% calories) fed groups
      (n=10 for each group). All rats underwent 12 weeks of feeding. After 4 weeks
      feeding, rats in the two of three HF diet fed groups were treated with 150 mg.kg
      1.day-1 BBR (HF+LBBR group) and 380 mg.kg-1.day-1 BBR (HF+HBBR group) by gavage
      once a day respectively for the next 8 weeks while the rats in other groups
      treated with vehicle (NF+Veh and HF+Veh). Body weight and food intake were
      observed and recorded on daily basis. At the end of 12 weeks, the blood, liver,
      epididymal fat tissues and quadriceps femoris muscles were collected. Fasting
      insulin, plasma fasting glucose, serum free fatty acid (FFA), total adiponectin
      and HMW adiponectin levels were measured by enzyme linked immunosorbent assay
      method. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were
      performed to determine the insulinsensitizing. Meanwhile the homeostasis model
      assessment (HOMA) method was used to determine insulin resistance (HOMA-IR). The
      expressions of adipoR1, adipoR2 and adenosine monophophate activated protein
      kinase (AMPK) phosphorylation level in skeletal muscle and liver tissue were
      detected by Western blot. Liver and kidney toxicity were evaluated during
      treatment. RESULTS: The body weight of rats in high- or low-dose BBR group
      reduced as well as HOMA-IR, FFA concentrations and fasting insulin levels
      decreased compared with HF+Veh group (P<0.05). BBR also increased the ratio of
      HMW to total adiponectin in high fat-fed rats compared with rats in the HF+Veh
      group. High- and low-dose BBR increased adipoR1 expression in skeletal muscle by
      over 6- and 2-fold (P<0.05), respectively, and high-dose BBR also increased
      adipoR2 expression in liver tissue by over 2-fold (P<0.05). BBR significantly
      increased AMPK phosphorylation in HF diet rats compared with normal diet rats
      (P<0.05). The ratio of HMW to total adiponectin was inversely correlated with
      HOMA-IR (r=-0.52, P=0.001). Meantime, no liver and kidney toxicity was found in
      high fat-fed rats that treated by BBR. CONCLUSION: Berberine may improve insulin
      resistance by increasing the expression of adiponectin receptors and the ratio of
      HMW to total adiponectin.

PMID- 27896587
TI  - Psychological and Behavioral Issues in the Management of Migraine in Children and
      Adolescents.
AB  - PURPOSE OF REVIEW: It is sometimes assumed that children and adolescents with
      migraine have a psychiatric or behavioral comorbidity, a belief that can be
      stigmatizing. This review will examine the recent literature addressing this area
      to determine if pediatric and adolescent migraineurs are at increased risk for
      psychiatric comorbidity and to discuss management strategies. RECENT FINDINGS: A
      large systematic review of pediatric and adolescent studies concluded anxiety and
      depression were not associated with onset of recurrent headaches. Children with
      increasing migraine frequency have reduced school attendance. Pediatric
      migraineurs have mildly lower quality of life (QOL) scores than healthy peers but
      not abnormally low. Finally, children with higher migraine frequency as well as
      migraineurs with aura were more likely to report suicidal ideation. Migraine is a
      primary neurologic disorder. Migraine and psychiatric disorders may be comorbid;
      however, at this time, it can be difficult to clearly delineate some migraine
      features from psychiatric diagnoses with the current screening tools available.
      The majority of pediatric migraineurs do not have behavioral comorbidities;
      however, when such comorbidities occur, they should be addressed and
      appropriately managed. We need more accurate ways of delineating psychiatric and
      behavioral comorbidities from the migraine phenotype.

PMID- 27896588
TI  - Electrosprayed Myocet-like Liposomes: An Alternative to Traditional Liposome
      Production.
AB  - PURPOSE: Although doxorubicin (DXR) has been on the market for many years as an
      anti-cancer drug, a number of serious dose-limiting toxicities hinder its
      widespread use. To reduce the known toxicities of soluble DXR, various liposomes
      have been designed including Doxil, Caelyx, and Myocet. Myocet, a non-PEGylated
      liposomal formulation containing DXR, was found to reduce the toxicities
      associated with soluble DXR and has been used in Europe and Canada (but not the
      US) as a first line therapy. While regarded as successful, Myocet does have some
      formulation drawbacks including stability, drug release, and an arduous
      formulation and remote loading method for preparation. METHODS: Our lab has
      developed a liposomal electrospray process in which formulation and remote
      loading occurs continuously in one step, cutting down on the total time of
      production and increasing the drug retention in the liposomes with respect to
      more conventional methods. Electrosprayed Myocet-like liposomes were then tested
      in vitro for release kinetics and cytotoxicity with respect to a more
      conventional formulation method. RESULTS: Myocet-like liposomes manufactured via
      electrospray had similar DXR loadings, hydrodynamic diameters, morphologies, and
      cytotoxic profiles as their thin-film hydration counterparts, but their release
      profiles were drastically prolonged. CONCLUSIONS: Our findings indicate that
      electrospray is a viable manufacturing procedure to scalably produce Myocet-like
      liposomes that appear to be more stable than those formulated through thin-film
      hydration.

PMID- 27896589
TI  - Lipid Nanoparticles Loaded with an Antisense Oligonucleotide Gapmer Against Bcl-2
      for Treatment of Lung Cancer.
AB  - PURPOSE: Bcl-2 is an anti-apoptotic gene that is frequently overexpressed in
      human cancers. G3139 is an antisense oligonucleotide against bcl-2 that has shown
      limited efficacy in clinical trials. Here, we report the synthesis of a new
      antisense oligonucleotide containing additional chemical modifications and its
      delivery using nanoparticles. METHODS: An oligonucleotide G3139-GAP was
      synthesized, which has 2'-O-methyl nucleotides at the 5' and 3' ends based on a
      "gapmer" design. Furthermore, G3139-GAP was incorporated into lipid nanoparticles
      (LNPs) composed of DOTAP/egg PC/cholesterol/Tween 80. The LNP-loaded G3139-GAP
      was evaluated in A549 lung cancer cells both in vitro and in a murine xenograft
      model for biological activity and therapeutic efficacy. RESULTS: The LNPs showed
      excellent colloidal and serum stability, and high encapsulation efficiency for
      G3139-GAP. They have a mean particle diameter and zeta potential of 134 nm and
      9.59 mV, respectively. G3139-GAP-LNPs efficiently downregulated bcl-2 expression
      in A549 cells, as shown by 40% and 83% reduction in mRNA and protein levels,
      respectively. Furthermore, G3139-GAP-LNPs were shown to inhibit tumor growth,
      prolong survival, and downregulate tumor bcl-2 expression in an A549 murine
      xenograft tumor model. These data indicate that G3139-GAP-LNPs have excellent
      anti-tumor efficacy and warrant further evaluation.

PMID- 27896590
TI  - Improvement in Thermal Stability of Sucralose by gamma-Cyclodextrin Metal-Organic
      Frameworks.
AB  - PURPOSE: To explain thermal stability enhancement of an organic compound,
      sucralose, with cyclodextrin based metal organic frameworks. METHODS: Micron and
      nanometer sized basic CD-MOFs were successfully synthesized by a modified vapor
      diffusion method and further neutralized with glacial acetic acid. Sucralose was
      loaded into CD-MOFs by incubating CD-MOFs with sucralose ethanol solutions.
      Thermal stabilities of sucralose-loaded basic CD-MOFs and neutralized CD-MOFs
      were investigated using thermogravimetric analysis (TGA), differential scanning
      calorimetry (DSC) and high performance liquid chromatography with evaporative
      light-scattering detection (HPLC-ELSD). RESULTS: Scanning electron microscopy
      (SEM) and powder X-ray diffraction (PXRD) results showed that basic CD-MOFs were
      cubic crystals with smooth surface and uniform sizes. The basic CD-MOFs
      maintained their crystalline structure after neutralization. HPLC-ELSD analysis
      indicated that the CD-MOF crystal size had significant influence on sucralose
      loading (SL). The maximal SL of micron CD-MOFs (CD-MOF-Micro) was 17.5 +/- 0.9%
      (w/w). In contrast, 27.9 +/- 1.4% of sucralose could be loaded in nanometer-sized
      basic CD-MOFs (CD-MOF-Nano). Molecular docking modeling showed that sucralose
      molecules preferentially located inside the cavities of gamma-CDs pairs in CD
      MOFs. Raw sucralose decomposed fast at 90 degrees C, with 86.2 +/- 0.2% of the
      compound degraded within only 1 h. Remarkably, sucralose stability was
      dramatically improved after loading in neutralized CD-MOFs, with only 13.7 +/-
      0.7% degradation at 90 degrees C within 24 h. CONCLUSIONS: CD-MOFs efficiently
      incorporated sucralose and maintained its integrity upon heating at elevated
      temperatures.

PMID- 27896591
TI  - Design and In Vitro Evaluation of Bispecific Complexes and Drug Conjugates of
      Anticancer Peptide, LyP-1 in Human Breast Cancer.
AB  - PURPOSE: LyP-1, a nine-amino-acid tumor homing peptide, selectively binds to its
      cognate receptor, p32. Overexpression of p32 in certain tumors should allow use
      of LyP-1 as a targeting agent for the delivery of therapeutic or diagnostic
      agents. Peptide conjugates are developed for enhanced pre-targeting of MDA-MB-231
      breast cancer cells with peptide-antibody bispecific complexes and targeting with
      multiple-drug/-fluorophore-conjugated nano-polymers. METHODS: LyP-1-anti-DTPA
      bispecific antibody complexes (LyP-1-bsAbCx) were generated by conjugation of
      anti-DTPA antibody and LyP-1. LyP-1-doxorubicin (Dox), Dox-DTPA-succinyl
      polylysine (Dox-DSPL), Dox-DSPL-LyP-1, DTPA-Dox-poly glutamic acid (D-Dox-PGA) or
      DTPA-rhodamine conjugated polylysine (DSPL-RITC) were prepared. In vitro
      therapeutic efficacy and targeting by immunofluorescence in MDA-MB-231 breast
      cancer cells were assessed with Dox-LyP-1. Immunofluorescence visualization of
      cancer cells was evaluated after pretargeting with LyP-1-bsAbCx and targeting
      with DSPL-RITC. RESULTS: Cytotoxicity of Dox-LyP-1 conjugates was significantly
      greater than free doxorubicin (p < 0.0001). For fluorescent-labeled LyP-1,
      internalization occurred in 30 min in tumor cells. Fluorescence intensity of two
      step targeted cells showed that pretargeting with LyP-1-bsAbC, followed by
      targeting with DSPL-RITC was greater than non-pretargeted DSPL-RITC (p < 0.05).
      CONCLUSIONS: Peptide-conjugates are effective targeting agents for MDA-MB-231
      breast cancer cells in culture. LyP-1-bsAbCx and Dox-LyP-1 conjugates may allow
      development of novel targeted cancer therapy and diagnosis.

PMID- 27896592
TI  - Why Have Clinical Trials of Antioxidants to Prevent Neurodegeneration Failed? - A
      Cellular Investigation of Novel Phenothiazine-Type Antioxidants Reveals Competing
      Objectives for Pharmaceutical Neuroprotection.
AB  - PURPOSE: Only a fraction of the currently established low-molecular weight
      antioxidants exhibit cytoprotective activity in living cells, which is considered
      a prerequisite for their potential clinical usefulness in Parkinson's disease or
      stroke. Post hoc structure-activity relationship analyses have predicted that
      increased lipophilicity and enhanced radical stabilization could contribute to
      such cytoprotective activity. METHODS: We have synthesized a series of novel
      phenothiazine-type antioxidants exhibiting systematic variation in their
      lipophilicity and radical stabilization. Phenothiazine was chosen as lead
      structure for its superior activity at baseline. The novel compounds were
      evaluated for their neuroprotective potency in cell culture, and for their
      primary molecular targets. RESULTS: Lipophilicity was associated with enhanced
      cytoprotective activity, but only to a certain threshold (logP ~ 7).
      Benzannulation likewise produced improved cytoprotectants that exhibited very low
      EC50 values of ~8 nM in cultivated neuronal cells. Inhibition of global protein
      oxidation was the best molecular predictor of cytoprotective activity, followed
      by the inhibition of membrane protein autolysis. In contrast, the inhibition of
      lipid peroxidation in isolated brain lipids and the suppression of intracellular
      oxidant accumulation were poor predictors of cytoprotective activity, primarily
      as they misjudged the cellular advantage of high lipophilicity. CONCLUSIONS:
      Lipophilicity, radical stabilization and molecular weight appear to form an
      uneasy triangle, in which a slightly faulty selection may readily abolish
      neuroprotective activity.

PMID- 27896593
TI  - Biochemical and oxidative stress markers in the liver and kidneys of rats
      submitted to different protocols of anabolic steroids.
AB  - The objective of this study was to evaluate the effects of different protocols
      (P1, P2, and P3) of boldenone undecylenate (BU) and stanozolol (ST) on markers of
      liver and kidney function and variables of oxidative stress in these organs. For
      this, 54 male Wistar rats were divided into nine groups of six animals each. Each
      animal received intramuscularly 5.0 mg kg-1 of BU or ST once a week for 4 weeks
      (P1); 2.5 mg kg-1 of BU or ST once a week for 8 weeks (P2); and 1.25 mg kg-1 of
      BU or ST once a week for 12 weeks (P3). For each protocol, a control group was
      used, and they received 0.1 ml of olive oil intramuscularly. Blood and fragments
      of liver and kidney were collected for alanine aminotransferase activity (ALT),
      alkaline phosphatase, albumin, creatinine, cholesterol, total protein,
      triglycerides, urea, reactive oxygen species, thiobarbituric acid reactive
      substances, total thiols, and glutathione evaluation. The results show that the
      BU in doses of 5 (day 30) and 2.5 mg kg-1 (day 60) changes the ALT seric
      activity, possibly showing a hepatotoxic effect. High doses of BU may lead to
      increased levels of cholesterol (protocol P1) possibly due to inhibition of the
      normal steroid biosynthesis process. All protocols used caused changes in the
      redox balance of the organs studied (except in the liver, protocol P2), which
      indicates that these drugs might be harmful even at low doses.

PMID- 27896596
TI  - Haemodynamic and functional consequences of the iatrogenic atrial septal defect
      following Mitraclip therapy.
AB  - Percutaneous MitraClip placement for treatment of severe mitral regurgitation in
      high surgical risk patients is a commonly performed procedure and requires a
      transseptal puncture to reach the left atrium. The resulting iatrogenic atrial
      septal defect (iASD) is not routinely closed, yet the haemodynamic and functional
      consequences of a persisting defect are not fully understood. Despite positive
      effects such as acute left atrial pressure relief, persisting iASDs are
      associated with negative consequences, namely significant bidirectional shunting
      and subsequent worse clinical outcome. Percutaneous closure of the iASD may
      therefore be desirable in selected cases. In this review we discuss the available
      literature on this matter.

PMID- 27896594
TI  - Global cerebral ischemia due to circulatory arrest: insights into cellular
      pathophysiology and diagnostic modalities.
AB  - Circulatory arrest (CA) remains a major unresolved public health problem in the
      United States; the annual incidence of which is ~0.50 to 0.55 per 1000
      population. Despite seminal advances in therapeutic approaches over the past
      several decades, brain injury continues to be the leading cause of morbidity and
      mortality after CA. In brief, CA typically results in global cerebral ischemia
      leading to delayed neuronal death in the hippocampal pyramidal cells as well as
      in the cortical layers. The dynamic changes occurring in neurons after CA are
      still unclear, and predicting these neurological changes in the brain still
      remains a difficult issue. It is hypothesized that the "no-flow" period produces
      a cytotoxic cascade of membrane depolarization, Ca2+ ion influx, glutamate
      release, acidosis, and resultant activation of lipases, nucleases, and proteases.
      Furthermore, during reperfusion injury, neuronal death occurs due to the
      generation of free radicals by interfering with the mitochondrial respiratory
      chain. The efficacy of many pharmacological agents for CA patients has often been
      disappointing, reflecting our incomplete understanding of this enigmatic disease.
      The primary obstacles to the development of a neuroprotective therapy in CA
      include uncertainties with regard to the precise cause(s) of neuronal dysfunction
      and what to target. In this review, we summarize our knowledge of the
      pathophysiology as well as specific cellular changes in brain after CA and
      revisit the most important neurofunctional, neuroimaging techniques, and serum
      biomarkers as potent predictors of neurologic outcome in CA patients.

PMID- 27896597
TI  - Noradrenergic inhibition of spinal hyperexcitation elicited by cutaneous cold
      stimuli in rats with oxaliplatin-induced allodynia: electrophysiological and
      behavioral assessments.
AB  - We investigated the spinal action of noradrenaline on cold-elicited
      hyperexcitation detected in dorsal horn neurons of rats with allodynia induced by
      an oxaliplatin (6 mg/kg, i.p.) injection. In vivo extracellular recordings from
      the spinal dorsal horn showed that wide dynamic range neurons responded to
      cutaneous acetone (10 MUl) stimulation in normal rats, and cold-elicited firings
      in oxaliplatin-administered rats were increased with a longer duration,
      correlated with behavioral responses. These responses were significantly
      attenuated by spinal administration (50 MUM) of noradrenaline or its agonists,
      clonidine (alpha2), phenylephrine (alpha1) and isoprenaline (beta), in descending
      order of efficacy. Thus, the inhibitory effect of noradrenaline on spinal
      oxaliplatin-induced cold hyperexcitation is mediated mainly by activation of
      alpha2- and/or alpha1-adrenoceptors.

PMID- 27896598
TI  - Bacterial and fungal biofilm formation on anodized titanium alloys with fluorine.
AB  - Orthopaedic device-related infections are closely linked to biofilm formation on
      the surfaces of these devices. Several modified titanium (Ti-6Al-4V) surfaces
      doped with fluorine were studied in order to evaluate the influence of these
      modifications on biofilm formation by Gram-positive and Gram-negative bacteria as
      well as a yeast. The biofilm studies were performed according to the standard
      test method approved by ASTM (Designation: E2196-12) using the Rotating Disk
      Reactor. Four types of Ti-6Al-4V samples were tested; chemically polished (CP),
      two types of nanostructures containing fluorine, nanoporous (NP) and nanotubular
      (NT), and non-nanostructured fluorine containing samples (fluoride barrier
      layers, FBL). Different species of Gram-positive cocci, (Staphylococcus aureus
      and epidermidis), Gram-negative rods (Escherichia coli, Pseudomonas aeruginosa),
      and a yeast (Candida albicans) were studied. For one of the Gram-positive (S.
      epidermidis) and one of the Gram-negative (E. coli) species a statistically
      significant decrease in biofilm accumulation for NP and NT samples was found when
      compared with the biofilm accumulation on CP samples. The results suggest an
      effect of the modified materials on the biofilm formation.

PMID- 27896599
TI  - Inflammatory cell response to ultra-thin amorphous and crystalline hydroxyapatite
      surfaces.
AB  - It has been suggested that surface modification with a thin hydroxyapatite (HA)
      coating enhances the osseointegration of titanium implants. However, there is
      insufficient information about the biological processes involved in the HA
      induced response. This study aimed to investigate the inflammatory cell response
      to titanium implants with either amorphous or crystalline thin HA. Human
      mononuclear cells were cultured on titanium discs with a machined surface or with
      a thin, 0.1 MUm, amorphous or crystalline HA coating. Cells were cultured for 24
      and 96 h, with and without lipopolysaccharide (LPS) stimulation. The surfaces
      were characterized with respect to chemistry, phase composition, wettability and
      topography. Biological analyses included the percentage of implant-adherent cells
      and the secretion of pro-inflammatory cytokine (TNF-alpha) and growth factors
      (BMP-2 and TGF-beta1). Crystalline HA revealed a smooth surface, whereas the
      amorphous HA displayed a porous structure, at nano-scale, and a hydrophobic
      surface. Higher TNF-alpha secretion and a higher ratio of adherent cells were
      demonstrated for the amorphous HA compared with the crystalline HA. TGF-beta1
      secretion was detected in all groups, but without any difference. No BMP-2
      secretion was detected in any of the groups. The addition of LPS resulted in a
      significant increase in TNF-alpha in all groups, whereas TGF-beta1 was not
      affected. Taken together, the results show that thin HA coatings with similar
      micro-roughness but a different phase composition, nano-scale roughness and
      wettability are associated with different monocyte responses. In the absence of
      strong inflammatory stimuli, crystalline hydroxyapatite elicits a lower
      inflammatory response compared with amorphous hydroxyapatite.

PMID- 27896600
TI  - Bacterial metabolites from intra- and inter-species influencing thermotolerance:
      the case of Bacillus cereus and Geobacillus stearothermophilus.
AB  - Bacterial metabolites with communicative functions could provide protection
      against stress conditions to members of the same species. Yet, information
      remains limited about protection provided by metabolites in Bacillus cereus and
      inter-species. This study investigated the effect of extracellular compounds
      derived from heat shocked (HS) and non-HS cultures of B. cereus and Geobacillus
      stearothermophilus on the thermotolerance of non-HS vegetative and sporulating B.
      cereus. Cultures of B. cereus and G. stearothermophilus were subjected to HS (42
      or 65  degrees C respectively for 30 min) or non-HS treatments. Cells and
      supernatants were separated, mixed in a combined array, and then exposed to 50 
      degrees C for 60 min and viable cells determined. For spores, D values (85 and 95
      degrees C) were evaluated after 120 h. In most cases, supernatants from HS B.
      cereus cultures added to non-HS B. cereus cells caused their thermotolerance to
      increase (D 50 12.2-51.9) when compared to supernatants from non-HS cultures (D
      50 7.4-21.7). While the addition of supernatants from HS and non-HS G.
      stearothermophilus cultures caused the thermotolerance of non-HS cells from B.
      cereus to decrease initially (D 50 3.7-7.1), a subsequent increase was detected
      in most cases (D 50 18-97.7). In most cases, supernatants from sporulating G.
      stearothermophilus added to sporulating cells of B. cereus caused the
      thermotolerance of B. cereus 4810 spores to decline, whereas that of B. cereus
      14579 increased. This study clearly shows that metabolites in supernatants from
      either the same or different species (such as G. stearothermophilus) influence
      the thermotolerance of B. cereus.

PMID- 27896602
TI  - A Review of the Scientific Misconduct Inquiry Process, Ankara Chamber of
      Medicine, Turkey.
AB  - The aim of this study is to review the inquiry process used in scientific
      misconduct cases in the Ankara Chamber of Medicine between the years 1998 and
      2012. The violations of the "Disciplinary Regulations of the Turkish Medical
      Association" have been examined by keeping the names of the people, institutions,
      associations and journals secret. In total, 31 files have been studied and 11 of
      these files have been identified as related to scientific misconduct. The methods
      of inquiry, the decisions about the need for an investigation process, the types
      of scientific misconduct, and the adjudication processes have all been reported.
      Furthermore, the motives of researchers who made allegations, the study
      approaches of investigators, and the objections to the decisions about guilt and
      innocence have also been examined. Based on the findings obtained, the reasons
      for scientific misconduct and the distribution of responsibilities among the
      people in the inquiry process have been discussed. A major conclusion is the need
      to standardize the process of conducting inquiries about scientific misconduct
      cases for the regional chambers of medicine in Turkey.

PMID- 27896601
TI  - How are Editors Selected, Recruited and Approved?
AB  - The editors of scholarly journals have a duty to uphold and promote the highest
      standards of ethical conduct of research. They also have a responsibility to
      maintain the integrity of the literature, and to promote transparency and honesty
      in reporting research findings. In the process of screening manuscripts they
      receive for possible publication, editors have the obligation to report
      infractions to the institutions of offending authors, and request an
      investigation. Since editors can reject a paper on ethical grounds, they can be
      considered to be the guardians of ethics who should express high ethical
      standards in conducting and publishing their own research. An examination of
      several publishers' websites reveals no such requirement or clear selection
      criteria for journal editors. Therefore, we aim to discuss the factors that
      publishers, in a broad sense, should consider when selecting editors for
      scholarly journals and believe that such criteria should be made public to ensure
      accountability. This would restore some of the eroding public trust in
      disseminated research, fortify confidence in the composition and qualification of
      members of an editorial board, and help to protect the reputations of publishers
      and editors.

PMID- 27896603
TI  - Unethical Admissions: Academic Integrity in Question.
AB  - The increasing unethical practices of graduates' admissions have heightened
      concerns about the integrity of the academy. This article informs this important
      subject that affects the students, admission systems, and the entire scientific
      community, thus, representing an approach against scholarly black market
      activities including falsified documents and unethical practices by consultants
      and students' recruitment agencies.

PMID- 27896604
TI  - Plagiarism in Student Research: Responsibility of the Supervisors and Suggestions
      to Ensure Plagiarism Free Research.
AB  - Plagiarism is a serious threat plaguing the research in publication of science
      globally. There is an increasing need to address the issue of plagiarism
      especially among young researchers in the developing part of the world.
      Plagiarism needs to be earnestly discouraged to ensure a plagiarism free research
      environment. We provide further suggestions to combat student plagiarism at
      Master's level and the regulations/guidelines regarding plagiarism in India.

PMID- 27896605
TI  - Personalized Medicine in a New Genomic Era: Ethical and Legal Aspects.
AB  - The genome of two completely unrelated individuals is quite similar apart from
      minor variations called single nucleotide polymorphisms which contribute to the
      uniqueness of each and every person. These single nucleotide polymorphisms are of
      great interest clinically as they are useful in figuring out the susceptibility
      of certain individuals to particular diseases and for recognizing varied
      responses to pharmacological interventions. This gives rise to the idea of
      'personalized medicine' as an exciting new therapeutic science in this genomic
      era. Personalized medicine suggests a unique treatment strategy based on an
      individual's genetic make-up. Its key principles revolve around applied pharmaco
      genomics, pharmaco-kinetics and pharmaco-proteomics. Herein, the ethical and
      legal aspects of personalized medicine in a new genomic era are briefly
      addressed. The ultimate goal is to comprehensively recognize all relevant forms
      of genetic variation in each individual and be able to interpret this information
      in a clinically meaningful manner within the ambit of ethical and legal
      considerations. The authors of this article firmly believe that personalized
      medicine has the potential to revolutionize the current landscape of medicine as
      it makes its way into clinical practice.

PMID- 27896606
TI  - A 'Knowledge Ecologies' Analysis of Co-designing Water and Sanitation Services in
      Alaska.
AB  - Willingness to collaborate across disciplinary boundaries is necessary but not
      sufficient for project success. This is a case study of a transdisciplinary
      project whose success was constrained by contextual factors that ultimately
      favoured technical and scientific forms of knowledge over the cultural
      intelligence that might ensure technical solutions were socially feasible. In
      response to Alaskan Water and Sewer Challenge (AWSC), an international team with
      expertise in engineering, consultative design and public health formed in 2013 to
      collaborate on a two-year project to design remote area water and sanitation
      systems in consultation with two native Alaskan communities. Team members were
      later interviewed about their experiences. Project processes are discussed using
      a 'Knowledge Ecology' framework, which applies principles of ecosystems analysis
      to knowledge ecologies, identifying the knowledge equivalents of 'biotic' and
      'abiotic' factors and looking at their various interactions. In a positivist
      'knowledge integration' perspective, different knowledges are like Lego blocks
      that combine with other 'data sets' to create a unified structure. The knowledge
      ecology framework highlights how interactions between different knowledges and
      knowledge practitioners ('biotic factors') are shaped by contextual ('abiotic')
      factors: the conditions of knowledge production, the research policy and funding
      climate, the distribution of research resources, and differential access to
      enabling infrastructures (networks, facilities). This case study highlights the
      importance of efforts to negotiate between different knowledge frameworks,
      including by strategic use of language and precepts that help translate social
      research into technical design outcomes that are grounded in social reality.

PMID- 27896607
TI  - Obsolete Laws: Economic and Moral Aspects, Case Study-Composting Standards.
AB  - From the early days of philosophy, ethics and justice, there is wide consensus
      that the constancy of the laws establishes the legal system. On the other hand,
      the rate at which we accumulate knowledge is gaining speed like never before. Due
      to the recently increased attention of academics to climate change and other
      environmental issues, a lot of new knowledge has been obtained about carbon
      management, its role in nature and mechanisms regarding the formation and
      degradation of organic matter. A multidisciplinary techno-economic assessment of
      current composting standards and laws that took into account the current state of
      knowledge about carbon management was carried out as a case study. Economic and
      environmental damage caused by outdated laws was revealed. In addition, it was
      found that the introduction of the best composts into the market is permitted,
      causing additional negative environmental as well as economic impacts.

PMID- 27896608
TI  - Developing Tools to Counteract and Prevent Suicide Bomber Incidents: A Case Study
      in Value Sensitive Design.
AB  - Developers and designers make all sorts of moral decisions throughout an
      innovation project. In this article, we describe how teams of developers and
      designers engaged with ethics in the early phases of innovation based on case
      studies in the SUBCOP project (SUBCOP stands for 'SUicide Bomber COunteraction
      and Prevention'). For that purpose, Value Sensitive Design (VSD) will be used as
      a reference. Specifically, we focus on the following two research questions: How
      can researchers/developers learn about users' perspectives and values during the
      innovation process? and How can researchers/developers take into account these
      values, and related design criteria, in their decision-making during the
      innovation process? Based on a case study of several innovation processes in this
      project, we conclude the researchers/developers involved are able to do something
      similar to VSD (without them knowing about VSD or calling it 'VSD'), supported by
      relatively simple exercises in the project, e.g., meetings with potential end
      users and discussions with members of the Ethical Advisory Board of the project.
      Furthermore, we also found-possibly somewhat counterintuitively-that a
      commercial, with its focus on understanding and satisfying customers' needs, can
      promote VSD.

PMID- 27896609
TI  - Moral Polemics of Far-Reaching Economic Consequences of Antibiotics Overuse.
AB  - The unethical overuse of antibiotics to seek to achieve a shortening of the
      treatment period raises the cost of health services and poses a threat to
      humanity due to the gradual development of antibiotic resistance. Other
      consequences of our modern passion for antibiotics have appeared. Small
      concentrations of antibiotic residues in sewage waters slow down the metabolism
      of anaerobic microorganism thereby reducing the overall performance of the
      anaerobic fermentation used to detoxify and digest sewage and other collected
      organic wastes. Reduced biogas yields represents a serious threat to the energy
      self-sufficiency of some waste-water treatment plants, so it might change them
      from energy producers into energy consumers. Morally justifiable production of
      renewable energy from bio-waste is also threatened by antibiotic residues that
      remain in the bio-waste.

PMID- 27896610
TI  - Limited Awareness of the Essences of Certification or Compliance Markings on
      Medical Devices.
AB  - Medical devices have been long used for odiagnostic, therapeutic or
      rehabilitation purposes. Currently, they can range from a low-cost portable
      device that is often used for personal health monitoring to high-end
      sophisticated equipment that can only be operated by trained professionals.
      Depending on the functional purposes, there are different certification or
      compliance markings on the device when it is sold. One common certification
      marking is the Conformite Europeenne affixation but this has a range of
      certification mark numbering for a variety of functional purposes. While the
      regulators and medical device manufacturers understand the associated
      significance and clinical implications, these may not be apparent to the
      professionals (using or maintaining the device) and the general public. With
      portable healthcare devices and mobile applications gaining popularity, better
      awareness of certification marking will be needed. Particularly, there are
      differences in the allowed functional purposes and the associated cost
      derivations of devices with a seemingly similar nature. A preferred approach such
      as an easy-to-understand notation next to any certification marking on a device
      can aid in differentiation without the need to digest mountainous regulatory
      details.

PMID- 27896611
TI  - Is Ignorance of Climate Change Culpable?
AB  - Sometimes ignorance is an excuse. If an agent did not know and could not have
      known that her action would realize some bad outcome, then it is plausible to
      maintain that she is not to blame for realizing that outcome, even when the act
      that leads to this outcome is wrong. This general thought can be brought to bear
      in the context of climate change insofar as we think (a) that the actions of
      individual agents play some role in realizing climate harms and (b) that these
      actions are apt targets for being considered right or wrong. Are agents who are
      ignorant about climate change and the way their actions contribute to it excused
      because of their ignorance, or is their ignorance culpable? In this paper I
      examine these questions from the perspective of recent developments in the
      theories of responsibility for ignorant action and characterize their verdicts.
      After developing some objections to existing attempts to explore these questions,
      I characterize two influential theories of moral responsibility and discuss their
      implications for three different types of ignorance about climate change. I
      conclude with some recommendations for how we should react to the face of the
      theories' conflicting verdicts. The answer to the question posed in the title,
      then, is: "Well, it's complicated."

PMID- 27896612
TI  - Why Tu Youyou Makes Less Money Than Zhang Ziyi?
AB  - Scientists normally earn less money than many other professions which require a
      similar amount of training and qualification. The economic theory of marginal
      utility and cost-benefit analysis can be applied to explain this phenomenon.
      Although scientists make less money than entertainment stars, the scientists do
      research work out of their interest and they also enjoy a much higher reputation
      and social status in some countries.

PMID- 27896613
TI  - New Issues for New Methods: Ethical and Editorial Challenges for an Experimental
      Philosophy.
AB  - This paper examines a constellation of ethical and editorial issues that have
      arisen since philosophers started to conduct, submit and publish empirical
      research. These issues encompass concerns over responsible authorship, fair
      treatment of human subjects, ethicality of experimental procedures, availability
      of data, unselective reporting and publishability of research findings. This
      study aims to assess whether the philosophical community has as yet successfully
      addressed such issues. To do so, the instructions for authors, submission process
      and published research papers of 29 main journals in philosophy have been
      considered and analyzed. In light of the evidence reported here, it is argued
      that the philosophical community has as yet failed to properly tackle such
      issues. The paper also delivers some recommendations for authors, reviewers and
      editors in the field.

PMID- 27896614
TI  - Modulatory effects of Zn2+ ions on the toxicity of citrate- and PVP-capped gold
      nanoparticles towards freshwater algae, Scenedesmus obliquus.
AB  - Gold nanoparticles (GNPs) are widely used for medical purposes, both in
      diagnostics as well as drug delivery, and hence are prone to release and
      distribution in the environment. Thus, we have explored the effects of GNPs with
      two distinct surface capping (citrate and PVP), and three different sizes (16,
      27, and 37 nm) at 0.01-, 0.1-, and 1-mg L-1 concentrations on a predominant
      freshwater alga Scenedesmus obliquus in the sterile freshwater matrix. We have
      also investigated how an abundant metal ion from freshwater, i.e., Zn2+ ions may
      modulate the effects of the selected GNPs (40 nm, citrate, and PVP capped).
      Preliminary toxicity results revealed that gold nanoparticles were highly toxic
      in comparison to zinc ions alone. A significant modulation in the toxicity of Zn
      ions was not noticed in the presence of GNPs. In contrast, zinc ions minimized
      the toxicity produced by GNPs (both CIT-37 and PVP-37), despite its individual
      toxicity. Approximately, about 42, 33, and 25% toxicity reduction was noted at
      0.05-, 0.5-, and 5-mg L-1 Zn ions, respectively, for CIT-37 GNPs, while 31% (0.05
      mg L-1), 24% (0.5 mg L-1), and 9% (5 mg L-1) of toxicity reduction were noted for
      PVP-37 GNPs. Maximum toxicity reduction was seen at 0.05 mg L-1 of Zn ions.
      Abbott modeling substantiated antagonistic effects offered by Zn2+ ions on GNPs.
      Stability and sedimentation data revealed that the addition of zinc ions
      gradually induced the aggregation of NPs and in turn significantly reduced the
      toxicity of GNPs. Thus, the naturally existing ions like Zn2+ have an ability to
      modulate the toxicity of GNPs in a real-world environment scenario.

PMID- 27896615
TI  - Bioprospecting hot spring metagenome: lipase for the production of biodiesel.
AB  - Screening of metagenomic library from Taptapani Hot Spring (Odisha) yielded a
      positive lipase clone (pUC-lip479). Sequence analysis showed an ORF (RK-lip479)
      of 416 amino acid residues which was overexpressed in Escherichia coli BL21
      (DE3). Optimum pH and temperature of purified lipase RK-lip479 were 8.0 and 65 
      degrees C, respectively, and found to be stable over a pH range of 7.0-9.0 and
      temperatures 55-75  degrees C. RK-lip479 could hydrolyse a wide range of 4
      nitrophenyl esters (4-nitrophenyoctanoate, 4-nitrophenyldodecanoate, 4
      nitrophenylpalmitate, 4-nitrophenylmyristate and 4-nitrophenylstearate), and
      maximum activity was observed with 4-nitrophenyldodecanoate. RK-lip479 was
      resistant to many organic solvents, especially isopropanol, DMSO, methanol, DMF,
      ethanol, dichloromethane, acetone, glycerol and ethyl acetate. RK-lip479 also
      showed activity in the presence of monovalent (Na+ and K+), divalent (Mg2+, Mn2+,
      Ca2+, Hg2+, Cu2+, Co2+, Zn2+ and Ag2+ ) and trivalent cations (Fe3+ and Al3+).
      Yield of biodiesel production was in the range of 40-76% using various waste oils
      with RK-Lip479 under optimized conditions.

PMID- 27896616
TI  - Seasonal effects of pre-aeration on microbial processes for nitrogen removal in
      constructed wetlands.
AB  - Seasonal effects of pre-aeration on microbial nitrogen performance in constructed
      wetlands (CWs) involved with anaerobic ammonium oxidation (anammox) process were
      investigated in this study. Slow natural re-aeration rate was the inhibiting
      factor for total nitrogen removal in CW without pre-aeration, and partial
      nitrification was the main way for nitrite generation. Besides partial
      nitrification, pre-aeration provided nitrite generation in CWs with an
      alternative way: nitrate reduction. Advantage of pre-aeration of influent was
      much different under various temperature ranges. Mean temperature of 15  degrees
      C seemed to be the turning point. With a mean temperature of or higher than 15 
      degrees C, nitrate in the influent effectively improved nitrogen removal in CWs.
      With a mean temperature lower than 15  degrees C, the nitrate reduction process
      in CWs was greatly inhibited. The benefit of pre-aeration was weak under this
      temperature range. Seasonal aeration pattern for the pre-treatment of HSSF CWs
      might be a more energy-saving alternative in in-suit domestic sewage treatment.

PMID- 27896617
TI  - Comprehensive DNA Methylation and Mutation Analyses Reveal a Methylation
      Signature in Colorectal Sessile Serrated Adenomas.
AB  - Colorectal sessile serrated adenomas (SSA) are hypothesized to be precursor
      lesions of an alternative, serrated pathway of colorectal cancer, abundant in
      genes with aberrant promoter DNA hypermethylation. In our present pilot study, we
      explored DNA methylation profiles and examined selected gene mutations in SSA.
      Biopsy samples from patients undergoing screening colonoscopy were obtained
      during endoscopic examination. After DNA isolation and quality analysis, SSAs (n
      = 4) and healthy controls (n = 5) were chosen for further analysis. DNA
      methylation status of 96 candidate genes was screened by q(RT)PCR using Methyl
      Profiler PCR array system. Amplicons for 12 gene mutations were sequenced by GS
      Junior Instrument using ligated and barcoded adaptors. Analysis of DNA
      methylation revealed 9 hypermethylated genes in both normal and SSA samples. 12
      genes (CALCA, DKK2, GALR2, OPCML, PCDH10, SFRP1, SFRP2, SLIT3, SST, TAC1, VIM,
      WIF1) were hypermethylated in all SSAs and 2 additional genes (BNC1 and PDLIM4)
      were hypermethylated in 3 out of 4 SSAs, but in none of the normal samples. 2
      SSAs exhibited BRAF mutation and synchronous MLH1 hypermethylation and were
      microsatellite instable by immunohistochemical analysis. Our combined mutation
      and DNA methylation analysis revealed that there is a common DNA methylation
      signature present in pre-neoplastic SSAs. This study advocates for the use of DNA
      methylation as a potential biomarker for the detection of SSA; however, further
      investigation is needed to better characterize the molecular background of these
      newly recognized colorectal lesions.

PMID- 27896619
TI  - DQB1*060101 may contribute to susceptibility to immunoglobulin A nephropathy in
      southern Han Chinese.
AB  - Immunoglobulin A nephropathy (IgAN) is a common form of chronic
      glomerulonephritis with unknown pathogenesis. Accumulating evidences have shown
      the ethnic-specific association between certain human leukocyte antigen (HLA)
      alleles and IgAN susceptibility. This study was designed to explore the
      relationship between HLA-DQB1 alleles and disease susceptibility and clinical
      manifestations of patients with IgAN in southern Han Chinese. A PCR sequence
      based typing technique was used to detect HLA-DQB1 alleles in 217 IgAN patients
      and 229 healthy subjects. Clinical data were collected from each patient at the
      time of renal biopsy. Twenty HLA-DQB1 alleles were detected in IgAN patients and
      healthy subjects. High frequency of HLA-DQB1* 060101 and low frequency of HLA
      DQB1*030101 were observed in IgAN patients compared with healthy controls.
      Further stratification analysis revealed that the frequency of DQB1*060101 was
      significantly higher in patients with urine protein >= 1.0 g/24 h than in
      patients with urine protein < 1.0 g/24 h. In combination with our previous DRB1
      results, we also analyzed the association of DRB1-DQB1 haplotypes with IgAN. We
      found that the frequency of haplotype DRB1*090102-DQB1*060101 was significantly
      higher [odds ratio (OR) = 4.409, Pc = 0.016], whereas that of HLA-DRB1*070101
      DQB1*020101 was significantly lower (OR = 0.194, Pc = 0.016) compared with
      healthy controls. Our study indicated that HLA-DQB1*060101 alleles may be a
      potential predictor of high-risk IgAN susceptibility in Chinese Han population.

PMID- 27896618
TI  - Loss of liver kinase B1 causes planar polarity defects in cochlear hair cells in
      mice.
AB  - The tumor suppressor gene liver kinase B1 (LKB1), also called STK11, encodes a
      serine/threonine kinase. LKB1 plays crucial roles in cell differentiation,
      proliferation, and polarity. In this study, LKB1 conditional knockout mice
      (LKB1Pax2 CKO mice) were generated using Pax2-Cre mice to investigate the
      function of LKB1 in inner ear hair cells during early embryonic period. LKB1Pax2
      CKO mice died perinatally. Immunofluorescence and scanning electron microscopy
      revealed that stereociliary bundles in LKB1Pax2 CKO mice were clustered and
      misoriented, respectively. Moreover, ectopic distribution of kinocilium bundles
      resulting from abnormal migration of kinocilium was observed in the mutant mice.
      The orientation of stereociliary bundles and the migration of kinocilia are
      critical indicators of planar cell polarity (PCP) of hair cells. LKB1 deficiency
      in LKB1Pax2 CKO mice thus disrupted hair cell planar polarity during embryonic
      development. Our results suggest that LKB1 is required in PCP formation in
      cochlear hair cells in mice.

PMID- 27896620
TI  - Antimicrobial activity of topical agents against Propionibacterium acnes: an in
      vitro study of clinical isolates from a hospital in Shanghai, China.
AB  - This study aimed to compare the antimicrobial activities of topical agents
      against Propionibacterium acnes isolated from patients admitted to a hospital in
      Shanghai, China. The minimal inhibitory concentrations of the cultured P. acnes
      were determined in accordance with the Clinical and Laboratory Standards
      Institute. Susceptibilities to clindamycin and erythromycin were compared in
      terms of gender, age, disease duration, previous treatment, and disease severity.
      A total of 69 P. acnes strains were isolated from 98 patients (70.41%). The
      susceptibility to triple antibiotic ointment (neomycin/bacitracin/polymyxin B)
      and bacitracin was 100%. The susceptibility to fusidic acid was 92.7%. The
      resistance rates to neomycin sulfate, erythromycin, and clindamycin were 11.7%,
      49.3%, and 33.4%, respectively. The high resistance rate to clindamycin and
      erythromycin was significantly affected by gender, previous treatment, and
      disease severity rather than by age and disease duration. Topical antibiotics
      should not be used separately for long-term therapy to avoid multiresistance. The
      use of topical antibiotics should be determined by clinicians on the basis of
      clinical conditions.

PMID- 27896621
TI  - Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced
      segmental and systemic analgesia.
AB  - Previous studies have demonstrated the effects of different afferent fibers on
      electroacupuncture (EA)-induced analgesia. However, contributions of functional
      receptors expressed on afferent fibers to the EA analgesia remain unclear. This
      study investigates the roles of acid-sensing ion channel 3 (ASIC3) and transient
      receptor potential vanilloid 1 (TRPV1) receptors in EA-induced segmental and
      systemic analgesia. Effects of EA at acupoint ST36 with different intensities on
      the C-fiber reflex and mechanical and thermal pain thresholds were measured among
      the ASIC3-/-, TRPV1-/-, and C57BL/6 mice. Compared with C57BL/6 mice, the
      ipsilateral inhibition of EA with 0.8 C-fiber threshold (0.8Tc) intensity on C
      fiber reflex was markedly reduced in ASIC3-/- mice, whereas the bilateral
      inhibition of 1.0 and 2.0Tc EA was significantly decreased in TRPV1-/- mice. The
      segmental increase in pain thresholds induced by 0.3 mA EA was significantly
      reduced in ASIC3-/- mice, whereas the systemic enhancement of 1.0 mA EA was
      markedly decreased in TRPV1-/- mice. Thus, segmental analgesia of EA with lower
      intensity is partially mediated by ASIC3 receptor on Abeta-fiber, whereas
      systemic analgesia induced by EA with higher intensity is more likely induced by
      TRPV1 receptor on Adelta- and C-fibers.

PMID- 27896623
TI  - Effect of the new maternity insurance scheme on medical expenditures for
      caesarean delivery in Wuxi, China: a retrospective pre/post-reform case study.
AB  - Aiming to control rising medical expenditures and help improve China's healthcare
      systems, this study examined whether a cap-based medical insurance scheme with
      shared financial interest between the insurance and healthcare providers is
      effective in containing hospitals' C-section medical expenditures. We used 6547
      caesarean delivery case records from a teaching tertiary-level general public
      hospital located in Wuxi, China (2004-2013), and used the Chow test to
      investigate the possibility of significant variation in mean medical expenditures
      for caesarean deliveries pre- and post-reform. We also used paired sample t-tests
      and linear regression models to compare the mean medical expenditures between
      insured and uninsured women undergoing caesarean delivery during the post-reform
      period. After the scheme's implementation, medical expenditures for caesarean
      deliveries declined and the medical expenditures of women covered by the scheme
      were significantly lower than those of uninsured patients. These findings
      indicated the scheme's effectiveness in minimizing caesarean delivery
      expenditures. The cap-based medical insurance scheme with shared financial
      interest between insurance and healthcare providers would likely steer healthcare
      providers' behaviors in a more cost-effective direction.

PMID- 27896622
TI  - Caveolin proteins: a molecular insight into disease.
AB  - Caveolae are a kind of specific cystic structures of lipid rafts in the
      cytoplasmic membrane and are rich in cholesterol and sphingolipids. In recent
      years, many researchers have found that both caveolins and caveolae play a role
      in the development of various human diseases, including coronary heart disease,
      hypertension, and nervous system disorders. The specific mechanisms by which
      caveolins induce diseases have been a topic of interest. However, a number of
      detailed molecular mechanisms remain poorly understood. This article focuses on
      the relationship between caveolin proteins and human diseases and reviews the
      molecular mechanisms of caveolins in disease networks.

PMID- 27896624
TI  - Autologous bone marrow stem cell transplantation for the treatment of ulcerative
      colitis complicated with herpes zoster: a case report.
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel disease with continuous
      or recurrent symptoms. A 42-year-old male patient with intermittent diarrhea
      accompanied by bloody mucopurulent stools was admitted to our hospital. The
      diagnosis of UC was confirmed by a combination of laboratory examination,
      colonoscopy, and histological assay. The patient developed herpes zoster in the
      hospital, which challenged traditional treatments. Therefore, we performed an
      autologous bone marrow cells to modulate the immune system with his permission.
      Autologous bone marrow mononuclear cells were collected and injected locally into
      the bowel mucosa, and subsequently injected systemically through a peripheral
      vein. After the patient underwent auto bone marrow mononuclear cells
      transplantations twice, the patient's symptoms were alleviated. Furthermore, he
      recovered from hematochezia, and his hypersensitive C reactive protein decreased.
      Colonoscopy results showed reduced lesions and decreased areas with bleeding and
      edema in the sigmoid colon and rectum. No recurrence occurred in the subsequent
      two years, but long-time monitoring is still necessary for the prophylaxis of
      colorectal cancer.

PMID- 27896626
TI  - Cheyne-stokes respiration during wakefulness in patients with chronic heart
      failure.
AB  - PURPOSE: Cheyne-Stokes respiration (CSR) during sleep has been studied
      extensively in patients with chronic heart failure (CHF). Prevalence and
      prognostic significance of CSR during wakefulness in CHF, however, are largely
      unknown. METHODS: CSR during wakefulness with an apnea-hypopnea cut-off >=5/h and
      moderate to severe CSR with an apnea-hypopnea cutoff >=15/h were analyzed using
      polysomnographic recordings in 267 patients with stable CHF with reduced left
      ventricular (LV) ejection fraction at our institution. Primary endpoint during
      follow-up was heart transplant-free survival. RESULTS: Fifty of 267 patients
      (19%) had CSR during wakefulness and 73 of 267 patients (27%) had CSR during
      sleep. CSR during wakefulness was associated with advanced age, atrial
      fibrillation, decreased LV ejection fraction, increased LV end-diastolic
      diameter, brain natriuretic peptide, New York Heart Failure class, and CSR during
      sleep. During 43 months mean follow-up, 67 patients (25%) died and 4 patients
      (1%) underwent heart transplantation. Multivariate Cox analysis identified age,
      male gender, chronic kidney disease, and LV ejection fraction as predictors of
      reduced transplant-free survival. CSR during wakefulness with an apnea-hypopnea
      cutoff >=5/h as well as moderate to severe CSR while awake using an apnea
      hypopnea cutoff >=15/h did not predict reduced transplant-free survival
      independently from confounding factors. CONCLUSION: CSR during wakefulness
      appears to be a marker of heart failure severity.

PMID- 27896625
TI  - MRI Characterization in the Acute Phase of Experimental Subarachnoid Hemorrhage.
AB  - A number of mechanisms have been proposed for the early brain injury after
      subarachnoid hemorrhage (SAH). In this study, we investigated the radiographic
      characteristics and influence of gender on early brain injury after experimental
      SAH. SAH was induced by endovascular perforation in male and female rats.
      Magnetic resonance imaging was performed in a 7.0-T Varian MR scanner at 24 h
      after SAH. The occurrence and size of T2 lesions, ventricular dilation, and white
      matter injury (WMI) were determined on T2-weighted images (T2WI). The effects of
      SAH on heme oxygenase-1 and fibrin/fibrinogen were examined by Western blotting
      and immunohistochemistry. SAH severity was assessed using a MRI grading system,
      and neurological function was evaluated according to a modified Garcia's scoring
      system. T2 hyperintensity areas and enlarged ventricles were observed in T2WI
      coronal sections 24 h after SAH. The overall incidence of T2 lesions, WMI, and
      hydrocephalus was 54, 20, and 63%, respectively. Female rats had a higher
      incidence of T2 hyperintensity lesions and hydrocephalus, as well as larger T2
      lesion volumes and higher average ventricular volume. SAH rats graded at 3-4 (our
      previously validated MRI grading scale) had larger T2 lesion volumes, more
      hydrocephalus, and worse neurological function compared with those graded at 0-2.
      In conclusion, T2 lesion, WMI, and hydrocephalus were the most prevalent MRI
      characteristics 24 h after experimental SAH. The T2 lesion area matched with
      fibrinogen/fibrin positive staining in the acute phase of SAH. SAH induced more
      severe brain injury in females compared to males in the acute phase of SAH.

PMID- 27896627
TI  - N-[11C]Methyl-AMD3465 PET as a Tool for In Vivo Measurement of Chemokine Receptor
      4 (CXCR4) Occupancy by Therapeutic Drugs.
AB  - PURPOSE: Chemokine receptor 4 (CXCR4) is overexpressed in many cancers and a
      potential drug target. We have recently developed the tracer N-[11C]methyl
      AMD3465 for imaging of CXCR4 expression by positron emission tomography (PET). We
      investigated the pharmacokinetics of N-[11C]methyl-AMD3465 in rats bearing a C6
      tumor and assessed whether the CXCR4 occupancy by the drug Plerixafor(r) can be
      measured with this PET tracer. PROCEDURE: A subcutaneous C6 tumor was grown in
      Wistar rats. Dynamic N-[11C]methyl-AMD3465 PET scans with arterial blood sampling
      was performed in control rats and rats pretreated with Plerixafor(r) (30 mg/kg,
      s.c). The distribution volume (V T) of the tracer was estimated by compartment
      modeling with a two-tissue reversible compartment model (2TRCM) and by Logan
      graphical analysis. The non-displaceable binding potential (BPND) was estimated
      with the 2TRCM. Next, CXCR4 receptor occupancy of different doses of the drug
      Plerixafor(r) (0.5-60 mg/kg) was investigated. RESULTS: The tumor could be
      clearly visualized by PET in control animals. Pretreatment with 30 mg/kg
      Plerixafor(r) significantly reduced tumor uptake (SUV 0.65 +/- 0.08 vs. 0.20 +/-
      0.01, p < 0.05). N-[11C]Methyl-AMD3465 was slowly metabolized in vivo, with 70 +/
      7% of the tracer in plasma still being intact after 60 min. The tracer showed
      reversible in vivo binding to its receptor. Both 2TRCM modeling and Logan
      graphical analysis could be used to estimate V T. Pre-treatment with 30 mg/kg
      Plerixafor(r) resulted in a significant reduction in V T (2TCRM 0.87 +/- 0.10 vs.
      0.23 +/- 0.12, p < 0.05) and BPND (1.85 +/- 0.14 vs. 0.87 +/- 0.12, p < 0.01).
      Receptor occupancy by Plerixafor(r) was dose-dependent with an in vivo ED50 of
      12.7 +/- 4.0 mg/kg. Logan analysis gave comparable results. CONCLUSION: N
      [11C]Methyl-AMD3465 PET can be used to visualize CXCR4 expression and to
      calculate receptor occupancy. V T determined by Logan graphical analysis is a
      suitable parameter to assess CXCR4 receptor occupancy. This approach can easily
      be translated to humans and used for early drug development and optimization of
      drug dosing schedules.

PMID- 27896628
TI  - Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI.
AB  - PURPOSE: We optimized acido-chemical exchange saturation transfer (acidoCEST)
      magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe),
      and translated this method to the radiology clinic to evaluate tumor acidosis.
      PROCEDURES: A CEST-FISP MRI protocol was used to image a flank SKOV3 tumor model.
      Bloch fitting modified to include the direct estimation of pH was developed to
      generate parametric maps of tumor pHe in the SKOV3 tumor model, a patient with
      high-grade invasive ductal carcinoma, and a patient with metastatic ovarian
      cancer. The acidoCEST MRI results of the patient with metastatic ovarian cancer
      were compared with DCE MRI and histopathology. RESULTS: The pHe maps of a flank
      model showed pHe measurements between 6.4 and 7.4, which matched with the
      expected tumor pHe range from past acidoCEST MRI studies in flank tumors. In the
      patient with metastatic ovarian cancer, the average pHe value of three adjacent
      tumors was 6.58, and the most reliable pHe measurements were obtained from the
      right posterior tumor, which favorably compared with DCE MRI and
      histopathological results. The average pHe of the kidney showed an average pHe of
      6.73 units. The patient with high-grade invasive ductal carcinoma failed to
      accumulate sufficient agent to generate pHe measurements. CONCLUSIONS: Optimized
      acidoCEST MRI generated pHe measurements in a flank tumor model and could be
      translated to the clinic to assess a patient with metastatic ovarian cancer.

PMID- 27896629
TI  - Remote Limb Ischemic Preconditioning Protects Rats Against Cerebral Ischemia via
      HIF-1alpha/AMPK/HSP70 Pathway.
AB  - Remote limb ischemic preconditioning (RIPC) is a clinically feasible strategy to
      protect against ischemia/reperfusion injury, but the knowledge concerning the
      mechanism underlying RIPC is scarce. This study was performed to examine the
      effect of RIPC on brain tissue suffering from ischemia challenge and explore its
      underlying mechanism in a rat model. The animals were divided into four groups:
      Sham, middle cerebral artery occlusion (MCAO), RIPC, and MCAO+RIPC. We found that
      previous exposure to RIPC significantly attenuated neurological dysfunction and
      lessened brain edema in MCAO+RIPC group. Moreover, other important events were
      observed in MCAO+RIPC group, including substantial decrements in the
      concentrations of oxidative response indicators [malondialdehyde (MDA), 8-hydroxy
      2-deoxyguanosine (8-OHdG), and protein carbonyl], significant reductions in
      levels of inflammation mediators [myeloperoxidase (MPO), tumor necrosis factor-a
      (TNF-a), interleukin-1beta (IL-1beta), and IL-6], and significant decline in
      neuronal apoptosis revealed by a smaller number of TUNEL-positive cells.
      Interestingly, both MCAO and RIPC groups exhibited meaningful elevations in the
      levels of HIF-1a, HSP70, and AMP-activated protein kinase (AMPK) compared to Sham
      group, and previous exposure to RIPC further elevated the levels of HIF-1a,
      HSP70, and AMPK in MCAO+RIPC group. Furthermore, the administration of YC-1 (HIF
      1 inhibitor), 8-bAMP (AMPK inhibitor), and Quercetin (HSP70 inhibitor) to
      MCAO+RIPC rats demonstrated that HIF-1alpha/AMPK/HSP70 was involved in RIPC
      mediated protection against cerebral ischemia.

PMID- 27896630
TI  - The many faces of working memory and short-term storage.
AB  - The topic of working memory (WM) is ubiquitous in research on cognitive
      psychology and on individual differences. According to one definition, it is a
      small amount of information kept in a temporary state of heightened
      accessibility; it is used in most types of communication and problem solving.
      Short-term storage has been defined as the passive (i.e., non-attention-based,
      nonstrategic) component of WM or, alternatively, as a passive store separate from
      an attention-based WM. Here I note that much confusion has been created by the
      use by various investigators of many, subtly different definitions of WM and
      short-term storage. The definitions are sometimes made explicit and sometimes
      implied. As I explain, the different definitions may have stemmed from the use of
      a wide variety of techniques to explore WM, along with differences in theoretical
      orientation. By delineating nine previously used definitions of WM and explaining
      how additional ones may emerge from combinations of these nine, I hope to improve
      scientific discourse on WM. The potential advantages of clarity about definitions
      of WM and short-term storage are illustrated with respect to several ongoing
      research controversies.

PMID- 27896631
TI  - Selective weighting of action-related feature dimensions in visual working
      memory.
AB  - Planning an action primes feature dimensions that are relevant for that
      particular action, increasing the impact of these dimensions on perceptual
      processing. Here, we investigated whether action planning also affects the short
      term maintenance of visual information. In a combined memory and movement task,
      participants were to memorize items defined by size or color while preparing
      either a grasping or a pointing movement. Whereas size is a relevant feature
      dimension for grasping, color can be used to localize the goal object and guide a
      pointing movement. The results showed that memory for items defined by size was
      better during the preparation of a grasping movement than during the preparation
      of a pointing movement. Conversely, memory for color tended to be better when a
      pointing movement rather than a grasping movement was being planned. This pattern
      was not only observed when the memory task was embedded within the preparation
      period of the movement, but also when the movement to be performed was only
      indicated during the retention interval of the memory task. These findings reveal
      that a weighting of information in visual working memory according to action
      relevance can even be implemented at the representational level during
      maintenance, demonstrating that our actions continue to influence visual
      processing beyond the perceptual stage.

PMID- 27896633
TI  - Adverse orienting effects on visual working memory encoding and maintenance.
AB  - Visual working memory (VWM) representations can be strengthened by pre-cues
      presented before, and retro-cues presented after, the memory display, providing
      evidence that attentional orienting plays a role in memory encoding and
      maintenance. It is unknown whether attentional orienting to VWM stimuli can also
      have adverse effects (known as inhibition of return; IOR), as has been found for
      perceptual-cueing tasks. If so, this would provide further evidence for common
      attentional orienting mechanisms for mnemonic and perceptual representations. In
      Experiment 1, we used pre-cueing and demonstrated an increased encoding
      probability, but not precision, at short SOAs, but probability decreased at long
      SOAs, reminiscent of the classic IOR findings. In Experiment 2, we used retro
      cueing and showed that it improved memory performance, unless attention was cued
      back to the center of the display by a second cue. In this case, the deleterious
      effects were on precision, indicating that the item was still retained, but its
      quality of representation suffered. Together, these results provide further
      evidence for universal spatial attentional mechanisms operating on perceptual as
      well as mnemonic representations.

PMID- 27896634
TI  - TH9 cells in skin disorders.
AB  - Interleukin 9 secreting TH9 cells have been proposed as the latest addition to
      the family of T helper cell subsets. While a growing body of evidence from animal
      models points to important roles for these cells in allergic inflammation of the
      lung, autoinflammation of the gastrointestinal tract, and tumor immunity, their
      role in skin immunity and skin immunopathology remains poorly defined.
      Interestingly, studies of T helper cells from healthy humans suggest that TH9
      cells are predominantly skin-homing and skin-resident and that they are involved
      in protection against extracellular pathogens. Thus, TH9 cells have entered the
      stage as potential mediators of cutaneous pathology. However, under which
      conditions and by which mechanisms these cells contribute to skin immunity and
      disease still has to be investigated. Here, we review our current understanding
      of TH9 cells as skin-tropic T helper cells and their involvement in skin
      pathology. Further, we discuss open questions with regard to the intricate nature
      of interleukin 9 producing T helper cells.

PMID- 27896635
TI  - Discovery and initial characterization of Th9 cells: the early years.
AB  - The launch of the Th1/Th2 concept represented a decisive breakthrough concerning
      our understanding of how very diverse immune reactions can be regulated by
      functionally different T helper subpopulations via the secretion of different
      panels of cytokines. In this context, IL-9 was identified to be produced by T
      helper cell lines in addition to Th2 cytokines IL-4 and IL-5. Detailed analyses
      revealed that IL-9 production of mouse CD4+ T helper cells was dependent on a
      combination of IL-2, IL-4, and TGF-beta. Roughly a decade later, it was found
      that TGF-beta can also induce the development of CD4+ Treg cells. This finding
      engendered a series of studies on the central role of TGF-beta for cytokine
      mediated T helper cell differentiation which elucidated that IL-4 curbed the Treg
      cell-promoting effect of TGF-beta while TGF-beta impaired the Th2-promoting
      capacity of IL-4. Instead, TGF-beta in combination with IL-4 induced the
      development of CD4+ T helper cells that preferentially produced IL-9 and that
      were different from Th2 cells which originally were thought to be the main source
      of IL-9. In addition, adoptive transfer of such IL-9-producing CD4+ T helper
      cells was shown to cause the development of colitis and peripheral neuritis.
      Hence, the unique cytokine expression pattern in combination with the
      inflammatory in vivo phenotype led to the designation of Th9 cells as a new CD4+
      T helper subpopulation.

PMID- 27896632
TI  - Tactile suppression in goal-directed movement.
AB  - Sharing numerous characteristics with suppression in the other senses, tactile
      suppression is a reliable phenomenon that accompanies movement. By investigating
      the simplest of movements (e.g., finger flexions), early research tried to
      explain the origins of the phenomenon in terms of motor command generation
      together with sensory reafference. Here, we review recent research that has
      delved into (naturalistic) goal-directed movements. In connection with goal
      directed movement, tactile suppression is evident as a decrease in behavioural
      performance measured shortly prior to, and during, movement execution. It is also
      reflected in a consistent response bias highlighting the (perceptual) uncertainty
      of the movement. Goal-directed movement supports the forward model and
      establishes contextual influences as the defining influences on tactile
      suppression. Depending on the task at hand, people prioritize a certain percept
      during movement. Future research, we argue, should focus on studying naturalistic
      movements, or sequences of movements, that share a common meaning or goal.

PMID- 27896637
TI  - SEOM Clinical Guideline for the treatment of pancreatic cancer (2016).
AB  - Pancreatic cancer remains an aggressive disease with a 5 year survival rate of
      5%. Only 15% of patients with pancreatic cancer are eligible for radical surgery.
      Evidence suggests a benefit on survival with adjuvant chemotherapy (gemcitabine o
      fluourouracil) after R1/R0 resection. Adjuvant chemoradiotherapy is also a valid
      option in patients with positive margins. Borderline resectable pancreatic cancer
      is defined as the involvement of the mesenteric vasculature with a limited
      extension. These tumors are technically resectable, but with a high risk of
      positive margins. Neoadjuvant treatment represents the best option for achieving
      an R0 resection. In advanced disease, two new chemotherapy treatment schemes
      (Folfirinox or Gemcitabine plus nab-paclitaxel) have showed improvements in
      overall survival compared with gemcitabine alone. Progress in pancreatic cancer
      treatment will require a better knowledge of the molecular biology of this
      disease, focusing on personalized cancer therapies in the near future.

PMID- 27896636
TI  - TNF superfamily cytokines in the promotion of Th9 differentiation and
      immunopathology.
AB  - The tumor necrosis factor (TNF) receptors and their corresponding cytokine
      ligands have been implicated in many aspects of the biology of immune functions.
      TNF receptors have key roles during various stages of T cell homeostasis. Many of
      them can co-stimulate lymphocyte proliferation and cytokine production.
      Additionally, several TNF cytokines can regulate T cell differentiation,
      including promoting Th1, Th2, Th17, and more recently the newly described Th9
      subset. Four TNF family cytokines have been identified as regulators for IL-9
      production by T cells. OX40L, TL1A, and GITRL can promote Th9 formation but can
      also divert iTreg into Th9, while 4-1BBL seems to inhibit IL-9 production from
      iTreg and has not been studied for its ability to promote Th9 generation.
      Regulation of IL-9 production by TNF family cytokines has repercussions in vivo,
      including enhancement of anti-tumor immunity and immunopathology in allergic lung
      and ocular inflammation. Regulating T cell production of IL-9 through blockade or
      agonism of TNF family cytokine receptors may be a therapeutic strategy for
      autoimmune and allergic diseases and in tumor.

PMID- 27896638
TI  - SEOM Clinical Guideline for gastrointestinal sarcomas (GIST) (2016).
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      of the digestive tract, and this disease has served as a paradigmatic model for
      successful rational development of targeted therapies. The introduction of
      tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and
      advanced stages has remarkably improved the survival in a disease formerly deemed
      resistant to all systemic therapies. The Spanish Society of Medical Oncology
      (SEOM) guidelines provide a multidisciplinary and updated consensus for the
      diagnosis and treatment of GIST patients. We strongly encourage that the managing
      of these patients should be performed within multidisciplinary teams in reference
      centers.

PMID- 27896639
TI  - SEOM Clinical Guideline for bone metastases from solid tumours (2016).
AB  - Bone metastases are common in many advanced solid tumours, being breast,
      prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can
      produce skeletal-related events (SREs), defined as pathological fracture, spinal
      cord compression, need of bone irradiation or need of bone surgery, and
      hypercalcaemia. Patients with bone metastases experience pain, functional
      impairment and have a negative impact on their quality of life. Several imaging
      techniques are available for diagnosis of this disease. Bone-targeted therapies
      include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL
      monoclonal antibody. Both reduce the risk and/or delay the development of SREs in
      several types of tumours. Radium 233, an alpha-particle emitter, increases
      overall survival in patients with bone metastases from resistant castration
      prostate cancer. Multidisciplinary approach is essential and bone surgery and
      radiotherapy should be integrated in the treatment of bone metastases when
      necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical
      presentations, lab tests, imaging techniques for diagnosis and response
      assessment, bone-targeted agents, and local therapies, as radiation and surgery,
      and establishes recommendations for the management of patients with metastases to
      bone.

PMID- 27896640
TI  - Role of axillary ultrasound, magnetic resonance imaging, and ultrasound-guided
      fine-needle aspiration biopsy in the preoperative triage of breast cancer
      patients.
AB  - PURPOSE: Roughly two-thirds of early breast cancer cases are associated with
      negative axillary nodes and do not benefit from axillary surgery at all.
      Accordingly, there is an ongoing search for non-surgical staging procedures to
      avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging
      techniques with very high sensitivity (Se) and negative predictive value (NPV)
      could eventually replace SNB. We aimed to establish the role of axillary US and
      MRI, alone or in combination, associated with ultrasound-guided fine-needle
      aspiration biopsy (US-FNAB) in the prediction of axillary node involvement.
      METHODS/PATIENTS: Between January 2003 and September 2015, we included 1505 of
      the 1538 breast cancer patients attending our centres. All patients had been
      referred from a single geographical area. Axillary US, magnetic resonance imaging
      and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if
      required. RESULTS: 1533 axillary US examinations and 1351 axillary MRI studies
      were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value
      (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI,
      corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were
      combined, Sp and PPV slightly improved over individual tests alone. US-FNAB
      showed a 100% Sp and PPV, with a Se of 80%. CONCLUSION: We may confidently state
      that axillary US and US-FNAB have to be included in the preoperative work-up of
      breast cancer patients.

PMID- 27896642
TI  - SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea
      and vomiting (2016).
AB  - Chemotherapy-induced nausea and vomiting is one of the most worrisome adverse
      effects of chemotherapy for cancer patients. It can cause severe discomfort and
      affect the quality of life. In recent years, the incorporation of new drugs has
      increased the efficacy of antiemetic treatments in the control of emesis
      associated with chemotherapy. This guideline, in which we give some treatment
      recommendations with level of evidence and grade of recommendation, provides an
      update of the previously published guideline of the Spanish Society of Medical
      Oncology and represents our continued commitment to improving supportive care in
      cancer patients.

PMID- 27896641
TI  - SEOM Clinical Guideline of fertility preservation and reproduction in cancer
      patients (2016).
AB  - Chemotherapy and radiotherapy often result in reduced fertility in cancer
      patients. With increasing survival rates, fertility is an important quality-of
      life concern for many young cancer patients. Around 70-75% of young cancer
      survivors are interested in parenthood but the numbers of patients who access
      fertility preservation techniques prior to treatment are significantly lower.
      Moreover, despite existing guidelines, healthcare professionals do not address
      fertility preservation issues adequately. There is a critical need for
      improvements in clinical care to ensure patients are well informed about
      infertility risks and fertility preservation options and to support them in their
      reproductive decision-making prior to cancer treatment.

PMID- 27896643
TI  - A novel signaling role for miR-451 in esophageal tumor microenvironment and its
      contribution to tumor progression.
AB  - OBJECTIVE: We evaluated miR-451 expression in serum and tissue samples of
      esophageal squamous cell carcinoma (ESCC) patients. Then, we examined a secretory
      role of miR-451 in esophageal tumor microenvironment. METHODS: miR-451 expression
      was evaluated in 39 serum samples from esophageal SCC patients compared to 39
      normal individuals as well as 26 pairs of fresh-frozen tumor and adjacent normal
      tissues from patients with ESCC, using qRT-PCR. In a co-culture system of human
      normal fibroblasts (HFSF-PI3) and esophageal cancer cell line (KYSE-30), we
      evaluated exosomal miR-451 secretion into the conditioned medium (CM) of both
      cell lines. Then, we analyzed the effect of primiR-451-transfected fibroblasts on
      the migration potency of their neighboring KYSE-30 cells. RESULTS: We detected
      miR-451 over-expression in serum samples of esophageal cancer patients compared
      to the normal group (P = 0.005). Interestingly, fresh-frozen tumor tissues from
      the same patients showed miR-451 down-regulation compared to their adjacent
      normal counterparts (P = 0.043). Co-culturing the KYSE-30 cell line with normal
      fibroblasts significantly induced miR-451 exosomal secretion into the CM.
      Moreover, co-culture of KYSE-30 cell line with miR-451-over-expressing
      fibroblasts significantly induced migration tendency in KYSE-30 cell line
      compared to the mock-transfected fibroblasts (P < 0.0001). In this system, MIF
      expression (a validated target of miR-451) in the KYSE-30 cell line was increased
      although this alteration was not statistically significant (fold change = 4.44).
      CONCLUSIONS: Our data suggest that cancer-associated fibroblasts use exosomal miR
      451 as a signaling molecule to provide a favorable niche for tumor cell migration
      and cancer progression. Our findings provide new insights into the stromal role
      of miR-451 in the esophageal tumor microenvironment as a communicatory molecule
      and suggest a signaling role for miR-451 in extracellular matrix cross-talks.

PMID- 27896644
TI  - The Effects of Musical Training on Child Development: a Randomized Trial of El
      Sistema in Venezuela.
AB  - : Many studies have explored the links between music and children's outcomes;
      however, study designs have not been sufficiently rigorous to support causal
      findings. This study aims to assess the effects of a large-scale music program on
      children's developmental functioning in the context of high rates of exposure to
      violence. The paper describes the results of an experimental evaluation of
      Venezuela's National System of Youth and Children's Orchestras. The curriculum of
      the program, better known as "El Sistema," emphasizes social interactions through
      group instruction and group performances. The randomized control trial was
      conducted in 16 music centers between May 2012 and November 2013. In total, 2914
      children ages 6-14 participated in the experiment, with approximately half
      receiving an offer of admission to the program in September 2012 and half in
      September 2013. The treatment group children participated for one semester more
      than the control group children. After 1 year, full-sample ITT estimates indicate
      improved self-control (by 0.10 standard deviations) and reduced behavioral
      difficulties (by 0.08 standard deviations), both significant at 10% after
      controlling for multiple hypothesis testing. There were no full-sample effects on
      other domains. Sub-sample effects are larger among (1) children with less
      educated mothers and (2) boys, especially those exposed to violence at baseline.
      In the latter subgroup, we find lower levels of aggressive behavior. We find that
      the program improved self-control and reduced behavioral difficulties, with the
      effects concentrated among subgroups of vulnerable children. The results suggest
      the importance of devising mechanisms to target resources to the most vulnerable
      children. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02369315.

PMID- 27896645
TI  - Response to Letter to the Editor: Intragastric Balloon for Management of Severe
      Obesity: a Systematic Review.

PMID- 27896646
TI  - Improvement of Health-Related Quality of Life After Roux-en-Y Gastric Bypass
      Related to Weight Loss.
AB  - INTRODUCTION: Effect of bariatric surgery on health-related quality of life
      (HRQOL) varies greatly. This might be caused by the diversity in questionnaires
      used to assess HRQOL and the weight loss of the studied population. This study
      assesses the relationship between weight loss and HRQOL in primary Roux-en-Y
      gastric bypass (RYGB) patients by using an obesity-specific (impact of weight on
      quality of life-lite, IWQOL-lite) and a generic (RAND-36) questionnaire. METHODS:
      HRQOL and weight parameters were assessed before and 15 and 24 months after RYGB
      surgery. HRQOL was assessed by using IWQOL-lite (an obesity-specific
      questionnaire consisting of one total score and five domains) and RAND-36 (a
      generic questionnaire consisting of two subtotal scores, the physical health
      summary (PHS) and mental health summary (MHS), and nine scales). RESULTS: Two
      thousand one hundred thirty-seven patients were included. HRQOL improved
      significantly after RYGB. Preoperative BMI was negatively related to baseline PHS
      (p < 0.001) and IWQOL-lite total (p < 0.001). Percentage total weight loss (%TWL)
      was positively related to HRQOL score at both follow-up moments. Change in HRQOL
      from baseline to 24 months was related to %TWL at 24 months in both subtotals of
      RAND-36 and IWQOL-lite total score (p <= 0.001 in all). CONCLUSION: HRQOL
      improves after RYGB. Higher %TWL is related to greater improvement in HRQOL and
      better HRQOL 15 and 24 months after RYGB. The variance in the effect of RYGB
      surgery on HRQOL can be explained by the questionnaire used and weight loss of
      the population.

PMID- 27896647
TI  - Changes in Non-Diabetic Comorbid Disease Status Following Laparoscopic Vertical
      Sleeve Gastrectomy (LVSG) Versus Laparoscopic Roux-En-Y Gastric Bypass (LRYGB)
      Procedures: a Systematic Review of Randomized Controlled Trials.
AB  - PURPOSE: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic vertical
      sleeve gastrectomy (LVSG) have been proposed as cost-effective strategies to
      manage obesity-related chronic disease. The aim of this systematic review was to
      study the peer review literature regarding postoperative nondiabetic comorbid
      disease resolution or improvement reported from randomized controlled trials
      (RCTs) comparing LVSG and LRYGB procedures. MATERIAL AND METHODS: RCTs comparing
      postoperative comorbid disease resolution such as hypertension, dyslipidemia,
      obstructive sleep apnea, joint and musculoskeletal conditions, gastroesophageal
      reflux disease, and menstrual irregularities following LVSG and LRYGB were
      included for analysis. The studies were selected from PubMed, Medline, EMBASE,
      Science Citation Index, Current Contents, and the Cochrane database and reported
      on at least one comorbidity resolution or improvement. The present work was
      undertaken according to the Preferred Reporting Items of Systematic Reviews and
      Meta-Analyses (PRISMA). The Jadad method for assessment of methodological quality
      was applied to the included studies. RESULTS: Six RCTs performed between 2005 and
      2015 involving a total of 695 patients (LVSG n = 347, LRYGB n = 348) reported on
      the resolution or improvement of comorbid disease following LVSG and LRYGB
      procedures. Both bariatric procedures provide effective and almost comparable
      results in improving or resolving these comorbidities. CONCLUSIONS: This
      systematic review of RCTs suggests that both LVSG and LRYGB are effective in
      resolving or improving preoperative nondiabetic comorbid diseases in obese
      patients. While results are not conclusive at this time, LRYGB may provide
      superior results compared to LVSG in mediating the remission and/or improvement
      in some conditions such as dyslipidemia and arthritis.

PMID- 27896649
TI  - The micropapillary/hobnail variant of papillary thyroid carcinoma: A review of
      series described in the literature compared to a series from one southern Italy
      pathology institution.
AB  - Papillary thyroid carcinoma (PTC) has a good prognosis with a 10-yr survival
      greater than 90%. Recently, a micro-papillary pattern with hobnail appearance
      (MPHC) in PTC has been indicated as associated with poor prognosis, but this
      suggestion is based only on a few cases from geographical areas different from
      ours. Two-hundred ninety-nine consecutive PTC cases were collected between the
      years of 1992 and 2014 at our institution. The corresponding histologic sections
      (at least 6 for each case) were stained with hematoxylin and eosin and reviewed
      independently by two pathologists to reach a consensus on the identification and
      quantification of the MPHC. As done in other cohorts, parallel serial sections
      were stained with antisera for thyroglobulin, epithelial membrane antigen,
      thyroid-transcription-factor-1 and Ki 67. BRAF gene mutation at codon 600 and
      RET/PTC1 gene rearrangements were searched. A comparative statistical analysis
      was done between the present series and previously published series. Of the 295
      PTC, 124 (42.5%) were follicular, 104 (35%) classic, 34 (11.5%) sclerosing, 15
      (5%) tall cells, 10 (3.4%) Warthin-like, and 8 (2.7%) MPHC. Four MHPC cases (50%)
      harbored the BRAF V600E variant, while one was positive for RET/PTC1
      rearrangement. Our rate of MPHC-PTC (2.7%) is 2X to 8X greater than those
      reported previously for cohorts from North America + North Italy, Korea and
      Mexico. MPHC prognosis appears to be better compared to other cohorts, probably
      due to not only to the lower rate of the vascular invasion, but also to the
      smaller size of the MPHC-PTC nodule.

PMID- 27896648
TI  - Clinical and Metabolic Effects of Biliopancreatic Diversion Persist After
      Reduction of the Gastric Pouch and Elongation of the Common Alimentary Tract.
      Preliminary Report in a Series of Patients with a 10-Year Follow-Up.
AB  - BACKGROUND: Biliopancreatic diversion (BPD) is a bariatric technique burdened, in
      some instances, by clinical evidence of malabsorption and malnutrition, and by
      intractable diarrhea. OBJECTIVE: The objective of this study was to assess
      metabolic and nutritional effects on patients undergoing BPD and BPD plus
      revisional surgery because of side effects. METHODS: Thirty-five consecutive BPD
      patients underwent revisional surgery (elongation of the common limb from 50 to
      200 cm and reduction of the gastric pouch from 500 to 40 ml) after a median 48
      month period [48.3 +/- 9.17 months (mean +/- SD)] and were observed for a total
      period of 116.2 +/- 6.21 months; 88 patients only undergoing BPD (controls) were
      observed for 120 months. RESULTS: Revisional surgery significantly improved side
      effects of BPD, with resolution of clinical symptoms in most instances. After
      revisional surgery, patients had a further decrease of body weight. The effect on
      disappearance of diabetes mellitus (DM) was remarkable, with no difference
      between revisional surgery and BPD. Triglycerides and transaminases decreased in
      a similar way, while cholesterol levels differed significantly. Estimated
      glomerular filtration rate improved. Nutritional parameters were similarly
      affected. CONCLUSION: This study suggests that it is possible to maintain the
      clinical and metabolic effects of BPD after a revisional procedure that leads to
      lesser malabsorption and to a greater restriction of the stomach. In particular,
      the positive effects on DM still persist after revisional surgery. This approach
      should be kept in mind in the presence of significant side effects due, inter
      alia, to excessive malabsorption.

PMID- 27896650
TI  - Neuroprotection by Chlorpromazine and Promethazine in Severe Transient and
      Permanent Ischemic Stroke.
AB  - Previous studies have demonstrated depressive or hibernation-like roles of
      phenothiazine neuroleptics [combined chlorpromazine and promethazine (C + P)] in
      brain activity. This ischemic stroke study aimed to establish neuroprotection by
      reducing oxidative stress and improving brain metabolism with post-ischemic C + P
      administration. Sprague-Dawley rats were subjected to transient (2 or 4 h) middle
      cerebral artery occlusion (MCAO) followed by 6 or 24 h reperfusion, or permanent
      (28 h) MCAO without reperfusion. At 2 h after ischemia onset, rats received
      either an intraperitoneal (IP) injection of saline or two doses of C + P. Body
      temperatures, brain infarct volumes, and neurological deficits were examined.
      Oxidative metabolism and stress were determined by levels of ATP, NADH, and
      reactive oxygen species (ROS). Protein kinase C-delta (PKC-delta) and Akt
      expression were determined by Western blotting. C + P administration induced a
      neuroprotection in both transient and permanent ischemia models evidenced by
      significant reduction in infarct volumes and neurological deficits post-stroke. C
      + P induced a dose-dependent reduction in body temperature as early as 5 min post
      ischemia and lasted up to 12 h. However, reduction in body temperature either
      only slightly or did not enhance C + P-induced neuroprotection. C + P therapy
      improved brain metabolism as determined by increased ATP levels and NADH
      activity, as well as decreased ROS production. These therapeutic effects were
      associated with alterations in PKC-delta and Akt protein expression. C + P
      treatments conferred neuroprotection in severe stroke models by suppressing the
      damaging cascade of metabolic events, most likely independent of drug-induced
      hypothermia. These findings further prove the clinical potential for C + P
      treatment and may direct us closer towards the development of an efficacious
      neuroprotective therapy.

PMID- 27896652
TI  - The Long-Term Efficacy and Safety of Pyloroplasty Combined with Gastric
      Electrical Stimulation Therapy in Gastroparesis.
AB  - INTRODUCTION: Gastroparesis is delayed gastric emptying without mechanical
      obstruction. Symptomatic improvement can be 50-60% with gastric electrical
      stimulation. To address delayed gastric emptying, pyloroplasty was added. This
      study examines the long-term efficacy and safety of simultaneous gastric
      electrical stimulator implantation and pyloroplasty. METHODS: In this prospective
      single-arm trial conducted from 2012 to 2015, 27 [23 females; mean age 43 (22
      63)] gastroparesis patients who underwent simultaneous gastric electrical
      stimulator implantation with Heineke-Mikulicz pyloroplasty were studied. Six
      (25%) underwent simultaneous robot-assisted pyloroplasty and gastric electrical
      stimulator implantation. Diagnosis of gastroparesis was based on the 4-h gastric
      emptying test defined as >60% retention of isotope at 2 h and >10% at 4 h. Total
      symptom scores assessing severity of nausea, early satiety, bloating, vomiting,
      post-prandial fullness, and epigastric pain were obtained at baseline and at
      follow-up visits, ranging from 3 to 38 months (mean: 17). RESULTS: Follow-up data
      from 24 patients were available for analysis. There was 71% improvement in total
      symptom score on follow-up. Mean retention decreased by 29.6 and 48.7% at 2 and 4
      h and gastric emptying was normalized in 60%. There were no post-surgical
      complications. CONCLUSIONS: Combination of gastric electrical stimulator and
      pyloroplasty significantly accelerated gastric emptying and improved
      gastroparesis symptoms. Combining these two surgical therapies improves both
      subjective and objective endpoints in drug refractory gastroparesis.

PMID- 27896651
TI  - Postnatal Administration of Dizocilpine Inhibits Neuronal Excitability in PFC and
      Induces Social Deficits Detected by MiceProfiler.
AB  - Schizophrenia is a devastating mental disease with social deficit as its core
      component of negative symptoms, which could be induced in rodents by dizocilpine
      (MK-801), a noncompetitive NMDA receptor antagonist. NMDA receptors are highly
      expressed during the postnatal period. However, less attention has been paid to
      the effects of postnatal MK-801 administration on social interaction. In this
      study, we evaluated the effects of postnatal administration of MK-801 on social
      interaction and explored the possible mechanisms. Postnatal day-7 mice were
      intraperitoneally injected with MK-801 twice daily for 5 days, and their social
      interaction repertoire was monitored by a computerized video in the 10th week.
      The contact event, relative position event, stop-state, and dynamic event were
      analyzed with MiceProfiler automatic idTracker system. The results showed that MK
      801 reduced the number of the contact events, relative position events, and stop
      states, while increased the number and duration of dynamic events. These changes
      implied that MK-801-injected mice had indifference and lower motivation in social
      interaction and could be a useful model for studies on the social deficit of
      schizophrenia. The prefrontal cortex is the key region for social interaction
      behaviors. Slice patch clamp was performed to analyze the cellular excitability
      of prefrontal cortical neurons after postnatal treatment with MK-801 in mice. The
      results demonstrated that MK-801 injection reduced the frequency and amplitude of
      action potentials, but increased the frequency of miniature inhibitory
      postsynaptic currents. These data illustrated that the excitability of neurons in
      the prefrontal cortex was inhibited. Finally, immunoblotting data demonstrated
      that MK-801 significantly decreased the levels of sirtuin 1 (SIRT1) and
      phosphorylated protein kinase B (p-PKB) in the prefrontal cortex (both P < 0.05).
      Taken together, our results indicated that administration of MK-801 to postnatal
      mice induces social interaction deficits possibly due to inhibiting the neuronal
      excitability and decreasing the levels of SIRT1 and p-PKB in the prefrontal
      cortex.

PMID- 27896653
TI  - Clinical Characteristics of Stoma-Related Obstruction after Ileal Pouch-Anal
      Anastomosis for Ulcerative Colitis.
AB  - AIMS: We defined small bowel obstruction occurring around the limbs of the
      ileostomy as stoma-related obstruction (SRO) and investigated the clinical
      characteristics and predictive factors of SRO. METHODS: From January 2002 to
      March 2016, 309 consecutive patients who underwent ileal pouch-anal anastomosis
      (IPAA) for ulcerative colitis were enrolled. Two-stage IPAA with diverting
      ileostomy was analyzed. We assessed the possible associations between SRO and
      clinical factors. RESULTS: A total of 205 patients met the inclusion criteria.
      Fifty-three (25.8%) patients with SRO before ileostomy closure were identified
      for review. All patients with SRO were at least transiently resolved by
      intubation though orifice of ileostomy (98.1%) or nasally (3.7%). In 18 (33.9%)
      patients, the ileostomy was taken down ahead of schedule and the small bowel
      obstruction improved in all cases. Multivariate analysis revealed that age at
      surgery <16 years old and body mass index <21 were significant predictive factors
      for SRO (P = 0.013 and 0.0012, respectively). CONCLUSION: Younger age at surgery
      and low body mass index may be significant predictive factors for SRO after IPAA
      with diverting ileostomy in patients with ulcerative colitis.

PMID- 27896654
TI  - Bowel Preparation Is Associated with Reduced Morbidity in Elderly Patients
      Undergoing Elective Colectomy.
AB  - BACKGROUND: Bowel preparation in elderly patients is associated with physiologic
      derangements that may result in postoperative complications. The aim of this
      study is to determine the impact of bowel preparation on postoperative outcomes
      in elderly patients. METHODS: Patients age 75 years and older who underwent
      elective colectomy were identified from the 2012-2014 American College of
      National Surgical Quality Improvement Program (ACS-NSQIP database). Patients were
      grouped into no bowel preparation, mechanical bowel preparation (MBP), oral
      antibiotic preparation (OABP), or combined MBP + OABP. Logistic regression
      modeling was conducted to calculate risk-adjusted 30-day outcomes. RESULTS: There
      were 4829 patients included in the analysis. Morbidity was 34.3% in no bowel
      prep, 32.4% in MBP, 24.8% in OABP, and 24.6% in MBP + OABP groups (p < 0.001).
      The MBP + OABP group compared with no bowel prep was associated with reduced
      rates of anastomotic leak, ileus, superficial surgical site infection (SSI),
      organ space SSI, respiratory compromise, and reduced length of stay. There was no
      difference in the rate of acute kidney injury between the groups. CONCLUSION: MBP
      + OABP was associated with reduced morbidity compared with no bowel preparation
      in elderly patients undergoing elective colorectal resection. MBP alone was not
      associated with differences in outcomes compared with no bowel preparation. The
      use of MBP + OABP is safe and effective in elderly patients undergoing elective
      colectomy.

PMID- 27896655
TI  - Transhepatic Hilar Approach for Perihilar Cholangiocarcinoma: Significance of
      Early Judgment of Resectability and Safe Vascular Reconstruction.
AB  - In the most common surgical procedure for perihilar cholangiocarcinoma, the
      margin status of the proximal bile duct is determined at the final step. Our
      procedure, the transhepatic hilar approach, confirms a cancer-negative margin
      status of the proximal bile duct first. We first performed a partial hepatic
      parenchymal transection to expose the hilar plate, and then transected the
      proximal bile duct to confirm margin status. Then, divisions of the hepatic
      artery and portal vein of the future resected liver are performed, followed by
      the residual hepatic parenchymal transection. The transhepatic hilar approach
      offers a wide surgical field for safe resection and reconstruction of the portal
      vein in the middle of the hepatectomy. We reviewed 23 patients with perihilar
      cholangiocarcinoma who underwent major hepatectomy using our procedure from 2011
      to 2015. A combined vascular resection and reconstruction was carried out in 14
      patients (60.9%). R0 resection was achieved in 17 patients (73.9%), and the
      overall 3-year survival rate was 52.9% (median survival time 52.4 months). The
      transhepatic hilar approach is useful and practicable regardless of local tumor
      extension, enabling us to determine tumor resectability and perform safe
      resection and reconstruction of the portal vein early in the operation.

PMID- 27896656
TI  - Pancreatitis After Pancreatoduodenectomy Predicts Clinically Relevant
      Postoperative Pancreatic Fistula.
AB  - BACKGROUND: Morbidity after pancreas resection is still high with postoperative
      pancreatic fistulas (POPF) being the most frequent complication. However,
      exocrine insufficiency seems to protect from POPF. In clinical practice, patients
      showing increased postoperative systemic amylase concentrations appear to
      frequently develop POPF. We therefore retrospectively examined the occurrence of
      systemic amylase increase after pancreas resections and its association with the
      clinical course. PATIENTS AND METHODS: Perioperative data from 739 consecutive
      pancreas resections were assessed in a prospectively maintained SPSS database.
      Serum and drain amylase concentrations were determined by routine clinical
      chemistry. POPFs were graded into A-C according to ISGPF definitions. RESULTS: In
      patients with reduced serum amylase (n = 89) on day 1 after
      pancreatoduodenectomy, clinically relevant POPFs were not observed. In patients
      with normal serum amylase concentrations, clinically relevant POPFs occurred in 9
      %, while in 39 % of the patients with more than three times elevated amylase
      concentrations, a clinically relevant postoperative fistula was observed (p <
      0.001). Systemic hyperamylasemia detected on postoperative day 1 after
      pancreatoduodenectomy was further a good predictor for clinically relevant POPFs
      (AUROC = 0.797, p < 0.001). CONCLUSION: Patients with a high risk for developing
      clinically relevant POPFs can be identified on the first postoperative day by
      determining serum amylase.

PMID- 27896658
TI  - Poor Glycemic Control Is Associated with Failure to Complete Neoadjuvant Therapy
      and Surgery in Patients with Localized Pancreatic Cancer.
AB  - BACKGROUND: The impact of glycemic control in patients with pancreatic cancer
      treated with neoadjuvant therapy is unclear. METHODS: Glycated hemoglobin (HbA1c)
      values were measured in patients with localized pancreatic cancer prior to any
      therapy (pretreatment) and after neoadjuvant therapy prior to surgery
      (preoperative). HbA1c levels greater than 6.5% were classified as abnormal.
      Patients were categorized based on the change in HbA1c levels from pretreatment
      to preoperative: GrpA, always normal; Gr B, worsened; GrpC, improved; and GrpD,
      always abnormal. RESULTS: Pretreatment HbA1c levels were evaluable in 123
      patients; there were 67 (55%) patients in GrpA, 8 (6%) in GrpB, 22 (18%) in GrpC,
      and 26 (21%) in GrpD. Of the 123 patients, 92 (75%) completed all intended
      therapy to include surgery; 57 (85%) patients in GrpA, 4 (50%) patients in GrpB,
      16 (72%) patients in GrpC, and 15 (58%) patients in GrpD (p = 0.01). Elevated
      preoperative carbohydrate antigen 19-9 (CA19-9) (OR 0.22;[0.07-0.66]), borderline
      resectable (BLR) disease stage (OR 0.20;[0.01-0.45]) and abnormal preoperative
      HbA1c (OR 0.30;[0.11-0.90]) were negatively associated with completion of all
      intended therapy. Abnormal preoperative HbA1c was associated with a 2.74-fold
      increased odds of metastatic progression during neoadjuvant therapy (p = 0.08).
      CONCLUSIONS: Elevated preoperative HbA1c is associated with failure to complete
      neoadjuvant therapy and surgery and a trend for increased risk of metastatic
      progression.

PMID- 27896659
TI  - The Relationship Between Pulsatile Flow Impingement and Intraluminal Thrombus
      Deposition in Abdominal Aortic Aneurysms.
AB  - Direct numerical simulations were performed on four patient-specific abdominal
      aortic aneurysm (AAA) geometries and the resulting pulsatile blood flow dynamics
      were compared to aneurysm shape and correlated with intraluminal thrombus (ILT)
      deposition. For three of the cases, turbulent vortex structures impinged/sheared
      along the anterior wall and along the posterior wall a zone of recirculating
      blood formed. Within the impingement region the AAA wall was devoid of ILT and
      remote to this region there was an accumulation of ILT. The high wall shear
      stress (WSS) caused by the impact of vortexes is thought to prevent the
      attachment of ILT. WSS from impingement is comparable to peak-systolic WSS in a
      normal-sized aorta and therefore may not damage the wall. Expansion occurred to a
      greater extent in the direction of jet impingement and the wall-normal force from
      the continuous impact of vortexes may contribute to expansion. It was shown that
      the impingement region has low oscillatory shear index (OSI) and recirculation
      zones can have either low or high OSI. No correlation could be identified between
      OSI and ILT deposition since different flow dynamics can have similar OSI values.

PMID- 27896657
TI  - Performing the Difficult Cholecystectomy Using Combined Endoscopic and Robotic
      Techniques: How I Do It.
AB  - Laparoscopic cholecystectomy is the standard of care for cholelithiasis as well
      as cholecystitis. However, in the setting of Mirizzi syndrome or gangrenous
      cholecystitis where the critical view cannot be ascertained, subtotal
      cholecystectomy may be necessary. Using the robot-assisted approach, difficult
      cholecystectomies can be performed upfront without need for partial
      cholecystectomy. Even in the setting of Mirizzi syndrome where severe scarring
      and fibrosis are evident, definitive cholecystectomy and takedown of the
      cholechystocholedochal fistula can be performed in a safe and feasible fashion
      following successful endoscopic common bile duct stent placement. The purposes of
      this report are to review the history of Mirizzi syndrome as well as its
      traditional and novel treatment techniques and highlight technical pearls of the
      robotic approach to this diagnosis.

PMID- 27896660
TI  - Ayahuasca Exposure: Descriptive Analysis of Calls to US Poison Control Centers
      from 2005 to 2015.
AB  - BACKGROUND: Ayahuasca is a hallucinogenic plant preparation which usually
      contains the vine Banisteriopsis caapi and the shrub Psychotria viridis. This tea
      originates from the Amazon Basin where it is used in religious ceremonies.
      Because interest in these religious groups spreading as well as awareness of use
      of ayahuasca for therapeutic and recreational purposes, its use is increasing.
      Banisteriopsis caapi is rich in beta-carbolines, especially harmine,
      tetrahydroharmine and harmaline, which have monoamine oxidase inhibiting (MAOI)
      activity. Psychotria viridis contains the 5HT2A/2C/1A receptor agonist
      hallucinogen N,N-dimethyltryptamine (DMT). Usual desired effects include
      hallucination, dissociation, mood alteration and perception change. Undesired
      findings previously reported are nausea, vomiting, hypertension, and tachycardia.
      METHODS: All human exposure calls reported to the American Association of Poison
      Controls Centers' (AAPCC) National Poison Data System (NPDS) between September 1,
      2005 and September 1, 2015 were reviewed. Cases were filtered for specific plant
      derived ayahuasca-related product codes. Abstracted data included the following:
      case age and gender, exposure reason, exposure route, clinical manifestations,
      treatments given, medical outcomes and fatality. RESULTS: Five hundred and thirty
      eight exposures to ayahuasca botanical products were reported. The majority of
      the calls to poison control centers came from healthcare facilities (83%). The
      most common route of exposure was ingestion. Most cases were men (437, 81%, 95%
      CI 77.7% - 84.3%). The median age was 21 (IQR 18-29). Most exposures were acute.
      Three hundred thirty-seven (63%) were reported to have a major or moderate
      clinical effect. The most common clinical manifestations reported were
      hallucinations (35%), tachycardia (34%), agitation (34%), hypertension (16%),
      mydriasis (13%) and vomiting (6%). Benzodiazepines were commonly given (30%).
      There were 28 cases in the series who required endotracheal intubation (5%). Four
      cases were reported to have had a cardiac arrest and 7 a respiratory arrest.
      Twelve cases had a seizure. Reports of exposures called to poison centers
      appeared to increase during this period based on annual estimates. Three
      fatalities were reported. CONCLUSIONS: Ayahuasca use appears to be rising in the
      United States based on calls to poison control centers. While most use is
      reported to be safe and well tolerated, with possible beneficial effects, serious
      and life threatening adverse manifestations are possible. Most of the exposures
      reported to poison control centers were young people, more likely to be men and
      already in a healthcare facility. Further research, which includes comprehensive
      drug testing, will be needed to better identify the risks and effects of
      ayahuasca use.

PMID- 27896661
TI  - Erratum to: Breast reconstruction using free medial circumflex femoral artery
      perforator flaps: intraoperative anatomic study and clinical results.

PMID- 27896663
TI  - Significant Role of Segmental Duplications and SIDD Sites in Chromosomal
      Translocations of Hematological Malignancies: A Multi-parametric Bioinformatic
      Analysis.
AB  - Recurrent non-random chromosomal translocations are hallmark characteristics of
      leukemogenesis, and however, molecular mechanisms underlying these rearrangements
      are less explored. The fundamental question is, why and how chromosomes break and
      reunite so precisely in the genome. Meticulous understanding of mechanism leading
      to chromosomal rearrangement can be achieved by characterizing breakpoints. To
      address this hypothesis, a novel multi-parametric computational approach for
      characterization of major leukemic translocations within and around breakpoint
      region was performed. To best of our knowledge, this bioinformatic analysis is
      unique in finding the presence of segmental duplications (SDs) flanking
      breakpoints of all major leukemic translocation. Breakpoint islands (BpIs) were
      analyzed for stress-induced duplex destabilization (SIDD) sites along with other
      complex genomic architecture and physicochemical properties. Our study distinctly
      emphasizes on the probable correlative role of SDs, SIDD sites and various
      genomic features in the occurrence of breakpoints. Further, it also highlights
      potential features which may be playing a crucial role in causing double-strand
      breaks, leading to translocation.

PMID- 27896662
TI  - Investigating the Additive Interaction of QT-Prolonging Drugs in Older People
      Using Claims Data.
AB  - INTRODUCTION: Drugs that potentially prolong the QT interval carry the risk of
      life-threatening Torsades de pointes (TdP) ventricular arrhythmia. OBJECTIVE: The
      objective of this study was to investigate the potential additive risk for
      ventricular arrhythmia with concomitant prescriptions of QT-prolonging drugs.
      METHODS: Claims data for persons aged >=65 years between 2010 and 2012 in Germany
      were analyzed and all cases hospitalized for ventricular arrhythmia were
      selected. In a case-crossover analysis, exposure with QT-prolonging drugs
      according to the Arizona Center for Education and Research on Therapeutics
      (AZCERT) classification of 'known,' 'conditional,' and 'possible' TdP risk was
      determined in respective event and control windows preceding hospitalization.
      Conditional logistic regression was applied to derive odds ratios (ORs). RESULTS:
      Among 6,849,622 health-insured persons, we identified 2572 patients newly
      hospitalized for ventricular arrhythmia. Drugs with 'known' risk were more
      frequently prescribed in the event window than in the control window (309 vs.
      239; P < 0.001). The number of drugs with an attributed 'known' risk of TdP was
      significantly associated with hospitalization for ventricular arrhythmia (OR:
      2.22; 95% confidence interval [1.51-3.25]; P < 0.001), while increased risk
      estimates were also obtained upon categorization into one and two or more drugs
      compared with no drugs for the combined group of drug with 'known' (1.52 [1.16
      2.00]) and 'conditional' risk (2.20 [1.42-3.41]). Pairwise comparisons and trend
      tests based on these classification categories could not demonstrate a
      significantly increased risk of two or more drugs compared with one drug.
      CONCLUSION: Beyond suitable single-drug classifications for QT-associated risk
      estimation, the situation when there is co-prescription of several drugs appears
      to be complex and may not be extrapolated to all possible multi-drug
      combinations.

PMID- 27896664
TI  - Molecular Interactions, Structural Transitions and Alterations in SoxB Protein
      Due to SoxYZ Interaction from Two Distinct beta-Proteobacteria: An In silico
      Approach Towards the Thiosulfate Oxidation and Recycling of SoxY Protein.
AB  - Microbial oxidation-reduction reactions utilizing the environmental thiosulfate
      ions and mediated mainly by the sox operon are very much essential to maintain
      the sulfur balance in the environment. Majority of the previously documented wet
      laboratory studies show genetics behind the functionality of Sox proteins encoded
      by the sox operon. However, the molecular details of the involvements of the
      essential SoxB, SoxY and SoxZ proteins in the beta-proteobacteria have not yet
      been elucidated. In this work, an attempt was made to analyze the interaction
      profiles of the aforementioned SoxB, SoxY and SoxZ proteins to predict their
      roles in biological sulfur oxidation process. In order to establish the possible
      roles of these Sox proteins, we built the homology models of these proteins from
      the two different beta-proteobacteria Dechloromonas aromatica and Thiobacillus
      denitrificans. We then used molecular docking and simulation studies to further
      analyze the interaction profiles of these sox proteins. Our analyses revealed
      that SoxB protein from T. denitrificans exhibited steadier and stronger
      interactions with SoxYZ protein complex. On the other hand, SoxB protein from D.
      aromatica was found to exhibit a spontaneous interaction with greater DeltaG
      values and therefore was well documented to exhibit a dual role. This is the
      first research article to discern the molecular level of interaction profiles of
      SoxB with SoxYZ protein complex in the beta-proteobacteria D. aromatica and T.
      denitrificans during the oxidations of thiosulfate. It would further prompt the
      future investigation into the mutational impact on the sequential interaction
      pattern in sox operon.

PMID- 27896665
TI  - Ultrasound-guided thoracic paravertebral block by the paralaminar in-plane
      approach using a microconvex array transducer: methodological utility based on
      anatomical structures.
AB  - OBJECTIVE: We evaluated the analgesic feasibility of paralaminar in-plane (PL)
      approach for ultrasound-guided thoracic paravertebral block (USG-TPVB). As the
      needle trajectory was expected to be closely affected by the distance from the
      skin to the lamina-transverse process junction (LTPJ), we examined the
      correlativity between them on computed tomography (CT) or ultrasonography.
      METHODS: Thirty-two patients undergoing thoracotomy were recruited. We measured
      the distances between the skin and LTPJ using preoperative CT (S-L) and
      procedural ultrasonography (US-L). At the beginning and the end of the surgery,
      20 ml of 0.5% ropivacaine was injected. The level of sensory block and
      postoperative numerical pain rating scale (NRS) was assessed. Relationships among
      the measured parameters and the agreement of the needle depth (ND) with S-L and
      US-L were evaluated using Pearson's correlation coefficient and Bland-Altman
      analysis. RESULTS: S-L and US-L were strongly correlated with ND (r = 0.72 and r
      = 0.81, respectively) but not with BMI. The Bland-Altman analysis showed that the
      mean percent differences between the ND and S-L or ND and US-L were -9.6 and
      20.1%, respectively. Catheters were inserted 18.6 mm lateral from the midline on
      average. Analgesia extended to 3-5 dermatomes in 29 patients, and the median NRS
      was 2 at 1, 6, 12, and 24 h after surgery, respectively. CONCLUSIONS: We
      demonstrated that PL approach provided feasible analgesia for thoracotomy and the
      ND was significantly correlated with the morphometric values. This technique
      allowed for inner catheter insertion route targeting longer anteroposterior
      thoracic paravertebral space length; this may reduce potential risk of pleural
      puncture for USG-TPVB. Trial registry number This study was registered in the
      UMIN Clinical Trials Registry (UMIN-CTR). (URL: http://umin.ac.jp/ctr/ ,
      ID:UMIN000014821).

PMID- 27896666
TI  - Characteristics Associated with HPV Diagnosis and Perceived Risk for Cervical
      Cancer Among Unmarried, Sexually Active College Women.
AB  - Human papillomavirus (HPV) has been identified as the leading cause of cervical
      cancer. While HPV risk factors have been well studied, less is known about those
      with HPV and their perceptions about health ramifications. The purposes of this
      study were to examine unmarried college student women's (1) HPV diagnosis status
      and (2) perceived risk of getting cervical cancer in the next 5 years. Data were
      analyzed from 1106 unmarried, sexually active college women aged 18 to 26. Binary
      logistic regression compared HPV-related knowledge, vaccination-related
      perceptions, mandate support, healthcare utilization, sexual behaviors, and
      personal characteristics. Multinomial logistic regression was performed to assess
      the degree to which these factors were associated with perceived risk of cervical
      cancer diagnosis. Relative to those not diagnosed with HPV, participants who had
      more lifetime sex partners (P < 0.001), unprotected sex during last intercourse
      (P = 0.003), Pap test in the past year (P < 0.001), and perceived themselves to
      be at higher risk for cervical cancer (P < 0.001) were significantly more likely
      to be diagnosed with HPV. Those with HPV were more likely to support HPV
      vaccination mandates (P = 0.036) and have fewer friends vaccinated (P = 0.002).
      Participants who were uninsured (P = 0.011), diagnosed with HPV (P < 0.001), and
      had a family member (P < 0.001) or friend (P < 0.001) with cervical cancer were
      more likely to perceive themselves at risk for developing cervical cancer in the
      next 5 years. Findings indicate women with HPV, despite engaging in risky sexual
      behaviors, acknowledge their cervical cancer risk and may be strong advocates for
      HPV vaccination mandates to protect youth against this preventable virus.

PMID- 27896667
TI  - Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven
      Cases.
AB  - Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and
      has been well studied in that population. In contrast, it is rare in adults and
      is not as well characterized clinically and pathologically. Seven cases of adult
      rhabdomyosarcoma occurring in head and neck were retrieved from the archives of
      Department of Pathology and Division of Oral Pathology at University of
      Washington. Radiologic findings and clinical history, as well as pathologic
      findings from hematoxylin and eosin slides and immunohistochemistry for myogenic
      markers were reviewed. A total of seven cases of rhabdomyosarcoma (two embryonal,
      three alveolar and two pleomorphic subtype) were reviewed. Patient ages ranged
      from 18 to 57 years (median 21 years). Classic and unique histologic features for
      each subtype, including post-treatment morphologic changes, were identified.
      Clinical follow-up information was available for 4 patients. 3 of 4 patients
      experienced recurrence, including two with distant metastasis. One patient died
      of disease progression 41 months after presentation. Head and neck
      rhabdomyosarcoma in adults can manifest both classic and unique histologic
      features for each subtype. In addition, recurrence and distant metastasis were
      observed, suggesting aggressive clinical behavior regardless of subtype.

PMID- 27896668
TI  - Target-specific delivery of siRNA into hepatoma cells' cytoplasm by bifunctional
      carrier peptide.
AB  - RNA interference (RNAi) is among the most potential approach for the therapy of
      hepatocellular carcinoma and the major barrier hindering siRNA therapeutics is
      the low efficiency of delivery to the desired cells. The current study aimed at
      developing a novel peptide for more efficient hepatoma targeted siRNA delivery,
      by combining luteinizing hormone-releasing hormone with hepatoma targeting
      specificity and MPG?NLS with cytoplasm-delivery tendency. The developed
      bifunctional peptide LHRH-MPG?NLS and siRNA were mixed together and resulted in
      LHRH-MPG?NLS/siRNA polyplexes through self-assembly. The polyplexes were
      characterized by agarose gel retardation and dynamic light scatting analysis.
      Hepatoma targeting specificity was analyzed with the GE IN Cell Analyzer 2000
      High-Content Cellular Analysis System after cell transfection, and the effect of
      RNA interference was detected by RT-PCR. The results demonstrated that LHRH
      MPG?NLS was able to assemble with siRNA to form stable and nano-sized
      peptide/siRNA polyplexes, which could inhibit the expression of the target gene
      and was essentially non-cytotoxic, as compared with the commercial transfection
      reagent lipofectamine 2000.

PMID- 27896669
TI  - Detection of autoantibodies to DSF70/LEDGFp75 in Mexican Hispanics using multiple
      complementary assay platforms.
AB  - PURPOSE: Antinuclear autoantibodies (ANA) targeting the dense fine speckled
      antigen DFS70, also known as lens epithelium-derived growth factor p75
      (LEDGF/p75), are attracting attention due to their low frequency in systemic
      rheumatic diseases but increased frequency in clinical laboratory referrals and
      healthy individuals (HI). These ANA specifically recognize the stress protein
      DFS70/LEDGFp75, implicated in cancer, HIV-AIDS, and inflammation. While their
      frequency has been investigated in various ethnic populations, there is little
      information on their frequency among Hispanics/Latinos. In this study, we
      determined the frequency of anti-DFS70/LEDGFp75 autoantibodies in Mexican
      Hispanics using multiple detection platforms. METHODS: The frequency of anti
      DFS70/LEDGFp75 antibodies was determined in 171 individuals, including 71
      dermatomyositis (DM) patients, 47 rheumatoid arthritis (RA) patients, 30 obesity
      (OB) patients, and 23 HI. Antibody detection was achieved using four
      complementary assay platforms: indirect immunofluorescence, Western blotting,
      ELISA, and chemiluminescent immunoassay. RESULTS: We detected relatively low
      frequencies of anti-DFS70/LEDGFp75 antibodies in patients with DM (1.4%), RA
      (4.3%), and OB (6.6%), and elevated frequency (17.4%) in HI. A strong concordance
      between the different antibody detection platforms was observed. CONCLUSIONS: The
      low frequency of anti-DFS70/LEDGFp75 antibodies in Mexican patients with
      rheumatic diseases, but relatively higher frequency in HI, is consistent with
      previous observations with non-Hispanic populations, suggesting that geographic
      differences or ethnicity do not influence the frequency of these autoantibodies.
      Our results also highlight the importance of confirmatory assays for the accurate
      detection of these autoantibodies. Future studies with larger cohorts of healthy
      Hispanics/Latinos are needed to confirm if their anti-DFS70/LEDGFp75 antibody
      frequencies are significantly higher than in non-Hispanics.

PMID- 27896670
TI  - The activation of the IFNbeta induction/signaling pathway in porcine alveolar
      macrophages by porcine reproductive and respiratory syndrome virus is variable.
AB  - BACKGROUND: It has been recognized that the expression of type I interferon
      (IFNalpha/beta) may be suppressed during infection with porcine reproductive,
      respiratory syndrome virus (PRRSV). This causes profound negative effects on both
      the innate and adaptive immunity of the host resulting in persistence of
      infection. OBJECTIVE: Test the effects of PRRSV infection of porcine alveolar
      macrophages (PAMs), the main target cell, on the expression of interferon beta
      (IFNbeta) and downstream signaling events. METHODS: In order to examine those
      effects, PAMs harvested from lungs of healthy PRRSV-free animals were infected
      with virulent, attenuated, infectious clone-derived chimeric viruses, or field
      PRRS virus strains. Culture supernatants from the infected PAMs were tested for
      IFNbeta protein expression by means of indirect ELISA and for bioactivity by a
      vesicular stomatitis virus plaque reduction assay. The expression of the Mx
      protein was assayed to ascertain signaling events. RESULTS: These experiments
      demonstrated that PRRSV does induce variably, the expression of bioactive IFNbeta
      protein in the natural host cell. To further elucidate the effects of PRRSV
      infection on IFNbeta signaling, Mx-1 an interferon stimulated gene (ISG), was
      also tested for expression. Interestingly, Mx-1 expression by infected PAMs
      generally correlated with IFNbeta production. CONCLUSION: The results of this
      study demonstrate that the induction of IFNbeta and signaling in PAMs after PRRSV
      infection is variable.

PMID- 27896671
TI  - A comparison of the brainstem auditory evoked response in healthy ears of
      unilaterally deaf dogs and bilaterally hearing dogs.
AB  - AIMS: Auditory plasticity in response to unilateral deafness has been reported in
      various animal species. Subcortical changes occurring in unilaterally deaf young
      dogs using the brainstem auditory evoked response have not been evaluated yet.
      The aim of this study was to assess the brainstem auditory evoked response
      findings in dogs with unilateral hearing loss, and compare them with recordings
      obtained from healthy dogs. METHODS: Brainstem auditory evoked responses
      (amplitudes and latencies of waves I, II, III, V, the V/I wave amplitude ratio,
      wave I-V, I-III and III-V interpeak intervals) were studied retrospectively in
      forty-six privately owned dogs, which were either unilaterally deaf or had
      bilateral hearing. The data obtained from the hearing ears in unilaterally deaf
      dogs were compared to values obtained from their healthy littermates. RESULTS:
      Statistically significant differences in the amplitude of wave III and the V/I
      wave amplitude ratio at 75 dB nHL were found between the group of unilaterally
      deaf puppies and the control group. The recordings of dogs with single-sided
      deafness were compared, and the results showed no statistically significant
      differences in the latencies and amplitudes of the waves between left- (AL) and
      right-sided (AR) deafness. CONCLUSIONS: The recordings of the brainstem auditory
      evoked response in canines with unilateral inborn deafness in this study varied
      compared to recordings from healthy dogs. Future studies looking into
      electrophysiological assessment of hearing in conjunction with imaging modalities
      to determine subcortical auditory plasticity and auditory lateralization in
      unilaterally deaf dogs are warranted.

PMID- 27896672
TI  - miR-15b Inhibits the Progression of Glioblastoma Cells Through Targeting Insulin
      like Growth Factor Receptor 1.
AB  - The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years.
      miR-15b was reported to exert an anti-oncogenic role in the proliferation,
      migration, and invasion of diverse tumor cells. However, the mechanisms
      underlying miR-15b-mediated biology of glioblastoma are still unclear. In the
      present study, the expression of miR-15b was down-regulated in glioblastoma tumor
      tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R)
      expression became up-regulated in these tumor tissues and cells (all p < 0.001).
      Furthermore, IGF1R expression was inversely associated with miR-15b expression.
      Notably, patients with lower miR-15b expression have a much shorter survival
      period compared with high expression (log-rank test p = 0.045). In vitro data
      demonstrated that miR-15b mimics inhibited the proliferation, cell cycle arrest,
      and invasion of U87 and U251 cells. Besides, we validated IGF1R as a direct
      target of miR-15b using dual luciferase assays, and IGF1R plasmids partially
      abrogated miR-15b mimics inhibited cell proliferation. In vivo, miR-15b mimics
      indeed repressed cell proliferation in mouse xenograft model. In conclusion, our
      study demonstrated that miR-15b inhibits the progression of glioblastoma cells
      through targeting IGF1R, and miR-15b can be recommended as a tumor suppressor in
      the progression of glioblastoma.

PMID- 27896674
TI  - Editorial Comment: Symposium: 2015 Meetings of the Musculoskeletal Tumor Society
      and the International Society of Limb Salvage.

PMID- 27896673
TI  - The clinical safety, biodistribution and internal radiation dosimetry of
      [18F]AH113804 in healthy adult volunteers.
AB  - BACKGROUND: Quantitative biodistribution, venous blood and excretion data have
      been obtained following the intravenous bolus injection of AH113804 (18F)
      Injection in six healthy volunteers (HVs), four males and two females, up to
      approximately 5 h post-injection. For each subject, key organs and tissues were
      delineated and analytical fits were made to the image data as functions of time
      to yield the normalised cumulated activities. These were input to an internal
      radiation dosimetry calculation based upon the Medical Internal Radiation Dose
      (MIRD) schema for the Cristy-Eckerman adult male or female phantom. The absorbed
      doses per unit administered activity to the 24 MIRD-specified target organs were
      evaluated for an assumed 3.5-h urinary bladder voiding interval using the Organ
      Level INternal Dose Assessment/Exponential Modelling (OLINDA/EXM) code. The sex
      specific absorbed doses were then averaged, and the effective dose per unit
      administered activity was calculated. RESULTS: Excluding the remaining tissue
      category, the three source regions with the highest mean initial 18F activity
      uptake were the liver (18.3%), lung (5.1%) and kidney (4.5%) and the highest mean
      normalised cumulated activities were the urinary bladder contents and voided
      urine (1.057 MBq h/MBq), liver (0.129 MBq h/MBq) and kidneys (0.065 MBq h/MBq).
      The three organs/tissues with the highest mean sex-averaged absorbed doses per
      unit administered activity were the urinary bladder wall (0.351 mGy/MBq), kidneys
      (0.052 mGy/MBq) and uterus (0.031 mGy/MBq). CONCLUSIONS: AH113804 (18F) Injection
      was safe and well tolerated. Although the effective dose, 0.0298 mSv/MBq, is
      slightly greater than for other common 18F PET imaging radiopharmaceuticals, the
      biodistribution and radiation dosimetry profile remain favourable for clinical
      PET imaging.

PMID- 27896675
TI  - Editorial: JBJS, The Bone & Joint Journal, and Clinical Orthopaedics and Related
      Research Require Prospective Registration of Randomized Clinical Trials-Why Is
      This Important?

PMID- 27896676
TI  - What is the Incidence of Suicide in Patients with Bone and Soft Tissue Cancer? :
      Suicide and Sarcoma.
AB  - BACKGROUND: Patients with cancer in the United States are estimated to have a
      suicide incidence that is approximately twice that of the general population.
      Patients with bone and soft tissue cancer often have physical impairments and
      activity limitations develop that reduce their quality of life, which may put
      them at high risk for depression, anxiety, and suicidal ideation. To our
      knowledge, there have been no large studies determining incidence of suicide
      among patients with bone and soft tissue cancer; this information might allow
      screening of certain high-risk groups. QUESTIONS/PURPOSES: To determine (1) the
      incidence of suicide in patients with bone and soft tissue cancer, (2) whether
      the incidence of suicide is greater in patients with bone and soft tissue cancer
      than it is in the general US population, and (3) any demographic and tumor
      characteristics associated with increased suicide incidence. METHODS: A
      retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER)
      program was performed. A total of 23,620 patients with primary bone and soft
      tissue cancer were identified in this database from 1973 and 2013. Patients with
      a cause of death listed as "suicide and self-inflicted injury" were considered to
      have committed suicide and suicide incidences were determined for different
      demographic and tumor characteristics in this subset of patients. Patient data
      for age, gender, race, marital status, year of diagnosis, primary cancer site,
      cancer stage, course of treatment, and survival time were collected and analyzed.
      The incidence of suicide in patients with bone and soft tissue sarcoma was
      compared with the age-, gender-, and race-adjusted incidence of suicide in the
      general US population from 1970 to 2013 available from the National Center for
      Health Statistics through the SEER Program. RESULTS: The overall suicide
      incidence in this population was 32 per 100,000 person-years, which was higher
      than the age-, race-, and gender-adjusted US general population suicide incidence
      of 13 per 100,000 person-years. When compared with the incidence of suicide in
      matched subgroups of the general US population, a higher suicide incidence was
      observed in men (standardized mortality ratio [SMR], 2.49; 95% CI, 1.92-3.22; p <
      0.001), patients of white race (SMR, 2.68; 95% CI, 1.94-3.56; p < 0.001),
      patients 21 to 30 years old (SMR, 4.40; 95% CI, 3.44-5.54; p < 0.001) and 61 to
      70 years old (SMR, 3.27; 95% CI, 2.54-4.18; p < 0.001), patients with cancer of
      the vertebral column (SMR, 2.88; 95% CI, 2.13-3.83; p < 0.001) and pelvic bones
      (SMR, 2.75; 95% CI, 2.00-3.65; p < 0.001), and patients within the first 5 years
      of cancer diagnosis (SMR, 10.8; 95% CI, 9.19-12.61; p < 0.001). CONCLUSIONS: With
      identification of these characteristics that are associated with higher incidence
      of suicide, physicians should consider screening patients possessing these
      traits. By identifying at-risk patients, we can hope to reduce the incidence of
      suicide in this population by providing the treatment that these patients need.
      Further research must be done to determine how best to screen these patients and
      to identify the best interventions to reduce suicide incidence. LEVEL OF
      EVIDENCE: Level III, prognostic study.

PMID- 27896677
TI  - Results of Database Studies in Spine Surgery Can Be Influenced by Missing Data.
AB  - BACKGROUND: National databases are increasingly being used for research in spine
      surgery; however, one limitation of such databases that has received sparse
      mention is the frequency of missing data. Studies using these databases often do
      not emphasize the percentage of missing data for each variable used and do not
      specify how patients with missing data are incorporated into analyses. This study
      uses the American College of Surgeons National Surgical Quality Improvement
      Program (ACS-NSQIP) database to examine whether different treatments of missing
      data can influence the results of spine studies. QUESTIONS/PURPOSES: (1) What is
      the frequency of missing data fields for demographics, medical comorbidities,
      preoperative laboratory values, operating room times, and length of stay recorded
      in ACS-NSQIP? (2) Using three common approaches to handling missing data, how
      frequently do those approaches agree in terms of finding particular variables to
      be associated with adverse events? (3) Do different approaches to handling
      missing data influence the outcomes and effect sizes of an analysis testing for
      an association with these variables with occurrence of adverse events? METHODS:
      Patients who underwent spine surgery between 2005 and 2013 were identified from
      the ACS-NSQIP database. A total of 88,471 patients undergoing spine surgery were
      identified. The most common procedures were anterior cervical discectomy and
      fusion, lumbar decompression, and lumbar fusion. Demographics, comorbidities, and
      perioperative laboratory values were tabulated for each patient, and the percent
      of missing data was noted for each variable. These variables were tested for an
      association with "any adverse event" using three separate multivariate
      regressions that used the most common treatments for missing data. In the first
      regression, patients with any missing data were excluded. In the second
      regression, missing data were treated as a negative or "reference" value; for
      continuous variables, the mean of each variable's reference range was computed
      and imputed. In the third regression, any variables with > 10% rate of missing
      data were removed from the regression; among variables with <= 10% missing data,
      individual cases with missing values were excluded. The results of these
      regressions were compared to determine how the different treatments of missing
      data could affect the results of spine studies using the ACS-NSQIP database.
      RESULTS: Of the 88,471 patients, as many as 4441 (5%) had missing elements among
      demographic data, 69,184 (72%) among comorbidities, 70,892 (80%) among
      preoperative laboratory values, and 56,551 (64%) among operating room times.
      Considering the three different treatments of missing data, we found different
      risk factors for adverse events. Of 44 risk factors found to be associated with
      adverse events in any analysis, only 15 (34%) of these risk factors were common
      among the three regressions. The second treatment of missing data (assuming
      "normal" value) found the most risk factors (40) to be associated with any
      adverse event, whereas the first treatment (deleting patients with missing data)
      found the fewest associations at 20. Among the risk factors associated with any
      adverse event, the 10 with the greatest effect size (odds ratio) by each
      regression were ranked. Of the 15 variables in the top 10 for any regression, six
      of these were common among all three lists. CONCLUSIONS: Differing treatments of
      missing data can influence the results of spine studies using the ACS-NSQIP. The
      current study highlights the importance of considering how such missing data are
      handled. CLINICAL RELEVANCE: Until there are better guidelines on the best
      approaches to handle missing data, investigators should report how missing data
      were handled to increase the quality and transparency of orthopaedic database
      research. Readers of large database studies should note whether handling of
      missing data was addressed and consider potential bias with high rates or
      unspecified or weak methods for handling missing data.

PMID- 27896678
TI  - No Clinically Important Difference in Knee Scores or Instability Between
      Transtibial and Inlay Techniques for PCL Reconstruction: A Systematic Review.
AB  - BACKGROUND: It is unclear whether the biomechanical superiority of the inlay
      technique over the transtibial technique, arising from avoidance of the killer
      turn at the graft-tunnel margin of the proximal tibia during posterior cruciate
      ligament (PCL) reconstruction, leads to better knee scores or greater knee
      stability. QUESTIONS/PURPOSES: This systematic review was designed to compare
      Tegner and Lysholm scores, and posterior residual laxity of the knee, between
      single-bundle PCL reconstruction using transtibial and inlay techniques. METHODS:
      We searched MEDLINE(r), Embase(r), and the Cochrane Library for studies comparing
      Tegner and/or Lysholm scores and posterior residual laxity, in patients who
      underwent PCL single-bundle reconstruction with the transtibial and tibial inlay
      techniques. There were no restrictions on language or year of publication.
      Studies were included if they compared clinical outcomes in patients who
      underwent PCL single-bundle reconstruction with the transtibial and tibial inlay
      techniques; they simultaneously reported direct comparisons of transtibial and
      tibial inlay PCL single-bundle reconstruction; and their primary outcomes
      included comparisons of postoperative scores on knee outcome scales and posterior
      residual laxity. A total of seven studies (including 149 patients having surgery
      using a transtibial approach, and 148 with the tibial inlay approach) met the
      prespecified inclusion criteria and were analyzed in detail. RESULTS: Our
      systematic review suggested that there are no clinically important differences
      between the transtibial and the tibial inlay single-bundle PCL reconstruction in
      terms of Tegner or Lysholm scores. Of the five studies that assessed Lysholm
      scores, one favored the transtibial approach and four concluded no difference on
      this endpoint; however, the observed differences in all studies where differences
      were observed were quite small (< 7 of 100 points on the Lysholm scale), and
      likely not clinically important. Of the four studies that compared postoperative
      Tegner scores, three identified no differences between the approaches, while one
      favored the tibial inlay approach by a small margin (0.5 of 11 points) suggesting
      that there likely is no clinically important difference between the approaches in
      Tegner scores, either. Finally, we identified no difference between the
      approaches in terms of residual laxity, either among the seven studies that
      presented data using Telos radiographs, or the five that reported on patients
      with residual laxity greater than Grade 2 on a four-grade scale of posterior
      drawer testing (28/107 for transtibial and 26/97 for tibial inlay). CONCLUSION:
      We found no clinically important differences between the transtibial and tibial
      inlay approach for PCL reconstruction. Based on the best evidence now available,
      it appears that surgeons may select between these approaches based on clinical
      experience and the specific elements of each patient's presentation, since there
      do not appear to be important or obvious differences between the approaches with
      respect to knee scores or joint stability. Future randomized trials are needed to
      answer this question more definitively. LEVEL OF EVIDENCE: Level III, therapeutic
      study.

PMID- 27896681
TI  - Financial Impact of Direct-Acting Oral Anticoagulants in Medicaid: Budgetary
      Assessment Based on Number Needed to Treat.
AB  - BACKGROUND: Faced with rising healthcare costs, state Medicaid programs need
      short-term, easily calculated budgetary estimates for new drugs, accounting for
      medical cost offsets due to clinical advantages. OBJECTIVE: To estimate the
      budgetary impact of direct-acting oral anticoagulants (DOACs) compared with
      warfarin, an older, lower-cost vitamin K antagonist, on 12-month Medicaid
      expenditures for nonvalvular atrial fibrillation (NVAF) using number needed to
      treat (NNT). METHOD: Medicaid utilization files, 2009 through second quarter
      2015, were used to estimate OAC cost accounting for generic/brand statutory
      minimum (13/23%) and assumed maximum (13/50%) manufacturer rebates. NNTs were
      calculated from clinical trial reports to estimate avoided medical events for a
      hypothetical population of 500,000 enrollees (approximate NVAF prevalence *
      Medicaid enrollment) under two DOAC market share scenarios: 2015 actual and 50%
      increase. Medical service costs were based on published sources. Costs were
      inflation-adjusted (2015 US$). RESULTS: From 2009-2015, OAC reimbursement per
      claim increased by 173 and 279% under maximum and minimum rebate scenarios,
      respectively, while DOAC market share increased from 0 to 21%. Compared with a
      warfarin-only counterfactual, counts of ischemic strokes, intracranial
      hemorrhages, and systemic embolisms declined by 36, 280, and 111, respectively;
      counts of gastrointestinal hemorrhages increased by 794. Avoided events and
      reduced monitoring, respectively, offset 3-5% and 15-24% of increased drug cost.
      Net of offsets, DOAC-related cost increases were US$258-US$464 per patient per
      year (PPPY) in 2015 and US$309-US$579 PPPY after market share increase.
      CONCLUSIONS: Avoided medical events offset a small portion of DOAC-related drug
      cost increase. NNT-based calculations provide a transparent source of budgetary
      impact information for new medications.

PMID- 27896679
TI  - What Are the Biomechanical Properties of the Taylor Spatial FrameTM?
AB  - BACKGROUND: The Taylor Spatial FrameTM (TSF) is a versatile variant of the
      traditional Ilizarov circular fixator. Although in widespread use, little
      comparative data exist to quantify the biomechanical effect of substituting the
      tried-and-tested Ilizarov construct for the TSF hexapod system.
      QUESTIONS/PURPOSES: This study was designed to investigate the mechanical
      properties of the TSF system under physiologic loads, with and without the
      addition of a simulated bone model, with comparison to the standard Ilizarov
      frame. METHODS: The mechanical behaviors of three identical four-ring TSF and
      Ilizarov constructs were tested under levels of axial compression, bending, and
      rotational torque to simulate loading during normal gait. An acrylic-pipe
      fracture model subsequently was mounted, using fine wires and 5 mm half pins, and
      the testing was repeated. Load-deformation curves, and so rigidity, for each
      construct were calculated, with statistical comparisons performed using paired t
      tests. RESULTS: Under axial loading, the TSF was found to be less rigid than the
      Ilizarov frame (645 +/- 57 N/mm versus 1269 +/- 256 N/mm; mean difference, 623
      N/mm; 95% CI, 438.3-808.5 N/mm; p < 0.001), but more rigid under bending and
      torsional loads (bending: 42 +/- 9 Nm/degree versus 78 +/- 13 Nm/degree; mean
      difference, 37 Nm/degree; 95% CI, 25.0-47.9 Nm/degree; p < 0.001; torsion: 16 +/-
      2 Nm/degree versus 5 +/- 0.35 Nm/degree; mean difference, 11 Nm/degree; 95% CI,
      9.5-12.2 Nm/degree; p < 0.001). On mounting the bone models, these relationships
      broadly remained in the half-pin and fine-wire groups, however the half-pin
      constructs were universally more rigid than those using fine wires. This effect
      resulted in the TSF, using half pins, showing no difference in axial rigidity to
      the fine-wire Ilizarov (107 +/- 3 N/mm versus 107 +/- 4 N/mm; mean difference,
      0.05 N/mm; 95% CI, -6.99 to 7.1 N/mm; p > 0.999), while retaining greater bending
      and torsional rigidity. Throughout testing, a small amount of laxity was observed
      in the TSF construct on either side of neutral loading, amounting to 0.72 mm (+/
      0.37 mm) for a change in loading between -10 N and 10 N axial load, and which
      persisted with the addition of the synthetic fracture model. CONCLUSIONS: This
      study broadly shows the TSF construct to generate lower axial rigidity, but
      greater bending and torsional rigidity, when compared with the Ilizarov frame,
      under physiologic loads. The anecdotally described laxity in the TSF hexapod
      strut system was shown in vitro, but only at low levels of loading around
      neutral. It also was shown that the increased stiffness generated by use of half
      pins produced a TSF construct replicating the axial rigidity of a fine-wire
      Ilizarov frame, for which much evidence of good clinical and radiologic outcomes
      exist, while providing greater rigidity and so improved resistance to potentially
      detrimental bending and rotational shear loads. CLINICAL RELEVANCE: If replicated
      in the clinical setting, these findings suggest that when using the TSF, care
      should be taken to minimize the observed laxity around neutral with appropriate
      preloading of the construct, but that its use may produce constructs better able
      to resist bending and torsional loading, although with lower axial rigidity. Use
      of half pins in a TSF construct however may replicate the axial mechanical
      behavior of an Ilizarov construct, which is thought to be conducive to bone
      healing.

PMID- 27896680
TI  - What Does a Shoulder MRI Cost the Consumer?
AB  - BACKGROUND: More than 100 MRIs per 1000 inhabitants are performed in the United
      States annually, more than almost every other country. Little is known regarding
      the cost of obtaining an MRI and factors associated with differences in cost.
      QUESTIONS/PURPOSES: By surveying all hospital-owned and independent imaging
      centers in Iowa, we wished to determine (1) the cost to the consumer of obtaining
      a noncontrast shoulder MRI, (2) the frequency and magnitude of discounts
      provided, and (3) factors associated with differences in cost including location
      (hospital-owned or independent) and Centers for Medicare & Medicaid Services
      designation (rural, urban, and critical access). METHODS: There were 71 hospitals
      and 26 independent imaging centers that offered MRI services in Iowa. Each site
      was contacted via telephone and posed a scripted request for the cost of the
      technical component of a noncontrast shoulder MRI. Radiologists' reading fees
      were not considered. Statistical analysis was performed using standard methods
      and significance was defined as a probability less than 0.05. RESULTS: The mean
      technical component cost to consumers for an MRI was USD 1874 +/- USD 694 (range,
      USD 500-USD 4000). Discounts were offered by 49% of imaging centers, with a mean
      savings of 21%. Factors associated with increased cost include hospital-owned
      imaging centers (USD 2062 +/- USD 664 versus USD 1400 +/- USD 441 at independent
      imaging centers; p < 0.001; mean difference, USD 662; 95% CI, USD 351-USD 893)
      and rural imaging centers, unless designated as a critical access hospital (USD
      2213 +/- USD 668 versus USD 1794 +/- USD 680; p = 0.0202; mean difference, USD
      419; 95% CI, USD 66-USD 772). CONCLUSIONS: In Iowa, the cost to the consumer of a
      shoulder MRI is significantly less at independent imaging centers compared with
      hospital-owned centers. Referring physicians and healthcare consumers should be
      aware that there may be substantial price discrepancies between centers that
      provide advanced imaging services. LEVEL OF EVIDENCE: Level IV, Economic and
      decision analysis.

PMID- 27896683
TI  - Population Pharmacokinetics of an Extended-Release Formulation of Exenatide
      Following Single- and Multiple-Dose Administration.
AB  - Exenatide is a glucagon-like peptide-1 receptor agonist with both immediate- and
      extended-release (ER) formulations that are approved for the treatment of type 2
      diabetes mellitus. Long-term exposure from the ER formulation is achieved through
      slow peptide release from a degradable microsphere formulation. The goal of this
      analysis was to develop a pharmacokinetic model for the ER formulation following
      single and once-weekly multiple-dose administration. Pharmacokinetic data were
      collected from two clinical trials-one that evaluated single-dose administration
      of 2.5, 5, 7, and 10 mg of ER exenatide and a second that included weekly
      administration of 0.8 and 2 mg for 15 weeks. A population pharmacokinetic model,
      describing 1586 exenatide concentrations from 64 patients, was developed in the
      nonlinear mixed-effects modeling software program NONMEM. Pharmacokinetics of the
      ER formulation was described by a two-compartment model with linear and nonlinear
      elimination. The complex absorption profile was quantified using three
      simultaneous processes: a first-order process characterizing a rapid initial
      release and two series of transit compartments to describe the second (~3 weeks
      postinjection) and third phases of drug release (~7 weeks postinjection).
      Estimation of the combined single- and multiple-dose data adequately described
      the rise to steady-state (~8-10 weeks) and decline to undetectable concentrations
      that occurred about 10 weeks after treatment cessation. Thus, a population-based
      pharmacokinetic model was developed that provides a platform for future
      pharmacodynamic analyses with the ER formulation of exenatide.

PMID- 27896682
TI  - Methods of Power-Force-Velocity Profiling During Sprint Running: A Narrative
      Review.
AB  - The ability of the human body to generate maximal power is linked to a host of
      performance outcomes and sporting success. Power-force-velocity relationships
      characterize limits of the neuromuscular system to produce power, and their
      measurement has been a common topic in research for the past century.
      Unfortunately, the narrative of the available literature is complex, with
      development occurring across a variety of methods and technology. This review
      focuses on the different equipment and methods used to determine mechanical
      characteristics of maximal exertion human sprinting. Stationary cycle ergometers
      have been the most common mode of assessment to date, followed by specialized
      treadmills used to profile the mechanical outputs of the limbs during sprint
      running. The most recent methods use complex multiple-force plate lengths in
      ground to create a composite profile of over-ground sprint running kinetics
      across repeated sprints, and macroscopic inverse dynamic approaches to model
      mechanical variables during over-ground sprinting from simple time-distance
      measures during a single sprint. This review outlines these approaches
      chronologically, with particular emphasis on the computational theory developed
      and how this has shaped subsequent methodological approaches. Furthermore,
      training applications are presented, with emphasis on the theory underlying the
      assessment of optimal loading conditions for power production during resisted
      sprinting. Future implications for research, based on past and present
      methodological limitations, are also presented. It is our aim that this review
      will assist in the understanding of the convoluted literature surrounding
      mechanical sprint profiling, and consequently improve the implementation of such
      methods in future research and practice.

PMID- 27896684
TI  - Use of Spray-Dried Dispersions in Early Pharmaceutical Development: Theoretical
      and Practical Challenges.
AB  - Spray-dried dispersions (SDDs) have become an important formulation technology
      for the pharmaceutical product development of poorly water-soluble (PWS)
      compounds. Although this technology is now widely used in the industry,
      especially in the early-phase development, the lack of mechanistic understanding
      still causes difficulty in selecting excipients and predicting stability of SDD
      based drug products. In this review, the authors aim to discuss several
      principles of polymer science pertaining to the development of SDDs, in terms of
      selecting polymers and solvents, optimizing drug loading, as well as assessing
      physical stability on storage and supersaturation maintenance after dissolution,
      from both thermodynamic and kinetic considerations. In order to choose compatible
      solvents with both polymers and active pharmaceutical ingredients (APIs), a
      symmetric Flory-Huggins interaction (Deltachi ~0) approach was introduced.
      Regarding spray drying of polymer-API solutions, low critical solution
      temperature (LCST) was discussed for setting the inlet temperature for drying. In
      addition, after being exposed to moisture, SDDs are practically converted to
      ternary systems with asymmetric Flory-Huggins interactions, which are
      thermodynamically not favored. In this case, the kinetics of phase separation
      plays a significant role during the storage and dissolution of SDD-based drug
      products. The impact of polymers on the supersaturation maintenance of APIs in
      dissolution media was also discussed. Moreover, the nature of SDDs, with
      reference to solid solution and the notion of solid solubility, was examined in
      the context of pharmaceutical application. Finally, the importance of robust
      analytical techniques to characterize the SDD-based drug products was emphasized,
      considering their complexity.

PMID- 27896685
TI  - The interactions of vanadate monomer with the mycelium of fungus Phycomyces
      blakesleeanus: reduction or uptake?
AB  - The possibility of reduction of vanadate monomer in the mycelium of fungus
      Phycomyces blakesleeanus was investigated in this study by means of polarography.
      Control experiments were performed with vanadyl [V(IV)] and vanadate [V(V)] in 10
      mM Hepes, pH 7.2. Addition of P. blakesleeanus mycelium resulted in disappearance
      of all V(IV) polarographic waves recorded in the control. This points to the
      uptake of all available V(IV) by the mycelium, up to 185 umol/gFW, and suggests
      P. blakesleeanus as a potential agent in V(IV) bioremediation. Polarographic
      measurements of mycelium with low concentrations (0.1-1 mM) of V(V), that only
      allows the presence of monomer, showed that fungal mycelia removes around 27% of
      V(V) from the extracellular solution. Uptake was saturated at 104 +/- 2 umol/gFW
      which indicates excellent bioaccumulation capability of P. blakesleeanus. EPR,
      51V NMR and polarographic experiments showed no indications of any measurable
      extracellular complexation of V(V) monomer with fungal exudates, reduction by the
      mycelium or adsorption to the cell wall. Therefore, in contrast to vanadium
      oligomers, vanadate monomer interactions with the mycelium are restricted to its
      transport into the fungal cell, probably by a phosphate transporter.

PMID- 27896686
TI  - Blastococcus colisei sp. nov, isolated from an archaeological amphitheatre.
AB  - The taxonomic position of an actinobacterial isolate, designated strain BMG 822T,
      isolated from limestone from the Amphitheater of El Jem (Coliseum Thysdrus),
      Tunisia, was established using a polyphasic approach. Strain BMG 822T was found
      to grow well at 30  degrees C and pH 6.5-8.0, and to be coral-coloured, Gram
      positive, catalase and oxidase negative. Whole cell hydrolysates contained meso
      diaminopimelic acid as the diagnostic diamino acid, glucose, galactose and
      ribose. The phospholipids detected were diphosphatidylglycerol,
      phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine, hydroxy
      phosphatidylethanolamine, an unidentified glycophospholipid and six unidentified
      phospholipids. MK-9(H4) was found to be the predominant menaquinone, followed by
      MK-9(H2) and MK-9. The major cellular fatty acids were identified as iso-C16:0,
      C18:1 omega9c, C17:1 omega8c and iso-H-C16:1. The G+C content of the DNA (73.2%)
      is typical of the genus. High degrees of 16S rRNA gene sequence similarity were
      found with the type strains of the genus Blastococcus (97.1-98.3%) followed by
      the type strains of Modestobacter (96.8-97.8%). Based on the above data and the
      phenotypic differences from the type strains of Blastococcus species, it is
      proposed that the isolate BMG 822T (=DSM 46837T=CECT 8823T) should be classified
      as the type strain of a novel species, Blastococcus colisei sp. nov.

PMID- 27896687
TI  - Evaluation of the influences of various force magnitudes and configurations on
      scoliotic curve correction using finite element analysis.
AB  - Scoliosis is a lateral curvature in the normally straight vertical line of the
      spine, and the curvature can be moderate to severe. Different treatment can be
      used based on severity and age of subjects, but most common treatment for this
      disease is using orthosis. To design orthosis types of force arrangement can be
      varied, from transverse loads to vertical loads or combination of them. But it is
      not well introduced how orthoses control scoliotic curve and how to achieve the
      maximum correction based on force configurations and magnitude. Therefore, it was
      aimed to determine the effect of various loads configurations and magnitudes on
      curve correction of a degenerative scoliotic subject. A scoliotic subject
      participated in this study. The CT-Scan of the subject was used to produce 3D
      model of spine. The 3D model of spine was produced by Mimics software and the
      finite element analysis and deformation of scoliotic curve of the spine under
      seven different forces and in three different conditions was determined by ABAQUS
      software. The Cobb angle in scoliosis curve decreased significantly by applying
      forces. In each condition depends on different forces, different corrections have
      been achieved. It can be concluded that the configurations of the force
      application mentioned in this study is effective to decrease the scoliosis curve.
      Although it is a case study, it can be used for a vast number of subjects to
      predict the correction of scoliosis curve before orthotic treatment. Moreover, it
      is recommended that this method and the outputs can be compared with clinical
      findings.

PMID- 27896688
TI  - Design, simulation and modelling of auxiliary exoskeleton to improve human gait
      cycle.
AB  - Exoskeleton is a walking assistance device that improves human gait cycle through
      providing auxiliary force and transferring physical load to the stronger muscles.
      This device takes the natural state of organ and follows its natural movement.
      Exoskeleton functions as an auxiliary device to help those with disabilities in
      hip and knee such as devotees, elderly farmers and agricultural machinery
      operators who suffer from knee complications. In this research, an exoskeleton
      designed with two screw jacks at knee and hip joints. To simulate extension and
      flexion movements of the leg joints, bearings were used at the end of hip and
      knee joints. The generated torque and motion angles of these joints obtained as
      well as the displacement curves of screw jacks in the gait cycle. Then, the human
      gait cycle was simulated in stance and swing phases and the obtained torque
      curves were compared. The results indicated that they followed the natural circle
      of the generated torque in joints with a little difference from each other. The
      maximum displacement obtained 4 and 6 cm in hip and knee joints jack
      respectively. The maximum torques in hip and knee joints were generated in foot
      contact phase. Also the minimum torques in hip and knee joints were generated in
      toe off and heel off phases respectively.

PMID- 27896689
TI  - Pharmacokinetics of Daratumumab Following Intravenous Infusion in Relapsed or
      Refractory Multiple Myeloma After Prior Proteasome Inhibitor and Immunomodulatory
      Drug Treatment.
AB  - Daratumumab is a CD38 monoclonal antibody recently approved for the treatment of
      multiple myeloma (MM). We report daratumumab pharmacokinetic data from GEN501, a
      phase I/II dose-escalation (0.005-24 mg/kg) and dose-expansion (8 or 16 mg/kg)
      study, and SIRIUS, a phase II study (8 or 16 mg/kg), in relapsed or refractory
      MM. Noncompartmental analysis was conducted to characterize daratumumab
      pharmacokinetics, and, in both studies, daratumumab exhibited nonlinear
      pharmacokinetic characteristics. Decreasing daratumumab clearance with increasing
      dose suggests saturation of target-mediated clearance at higher dose levels,
      whereas decreasing clearance over time with repeated dosing may be due to tumor
      burden reductions as CD38-positive cells are eliminated. These and other
      pharmacokinetic data analyses support the use of the recommended dose regimen of
      daratumumab (16 mg/kg weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4
      weeks thereafter) to rapidly saturate target-mediated clearance during weekly
      dosing and maintain saturation when dosing every 2 or 4 weeks.

PMID- 27896690
TI  - Elucidating the Plasma and Liver Pharmacokinetics of Simeprevir in Special
      Populations Using Physiologically Based Pharmacokinetic Modelling.
AB  - The disposition of simeprevir (SMV) in humans is characterised by cytochrome P450
      3A4 metabolism and hepatic uptake by organic anion transporting polypeptide 1B1/3
      (OATP1B1/3). This study was designed to investigate SMV plasma and liver exposure
      upon oral administration in subjects infected with hepatitis C virus (HCV), in
      subjects of Japanese or Chinese origin, subjects with organ impairment and
      subjects with OATP genetic polymorphisms, using physiologically based
      pharmacokinetic modelling. Simulations showed that compared with healthy
      Caucasian subjects, SMV plasma exposure was 2.4-, 1.7-, 2.2- and 2.0-fold higher,
      respectively, in HCV-infected Caucasian subjects, in healthy Japanese, healthy
      Chinese and subjects with severe renal impairment. Further simulations showed
      that compared with HCV-infected Caucasian subjects, SMV plasma exposure was 1.6
      fold higher in HCV-infected Japanese subjects. In subjects with OATP1B1 genetic
      polymorphisms, no noteworthy changes in SMV pharmacokinetics were observed.
      Simulations suggested that liver concentrations in Caucasians with HCV are 18
      times higher than plasma concentrations.

PMID- 27896691
TI  - A Pilot Study of the Chronology of Present Illness: Restructuring the HPI to
      Improve Physician Cognition and Communication.
AB  - BACKGROUND: Patient history-taking is an essential clinical skill, with effects
      on diagnostic reasoning, patient-physician relationships, and more. We evaluated
      the impact of using a structured, timeline-based format, the Chronology of
      Present Illness (CPI), to guide the initial patient interaction. OBJECTIVE: To
      determine the feasibility and impact of the CPI on the patient interview, written
      notes, and communication with other providers. DESIGN: Internal medicine
      residents used the CPI during a 2-week night-float rotation. For the first week,
      residents interviewed, documented, and presented patient histories according to
      their normal practices. They then attended a brief educational session describing
      the CPI, and were asked to use this method for new patient interviews, notes, and
      handoffs during the second week. Night and day teams evaluated the method using
      retrospective pre-post comparisons. PARTICIPANTS: Twenty-two internal medicine
      residents in their second or third postgraduate year. INTERVENTION: An
      educational dinner describing the format and potential benefits of using the CPI.
      MAIN MEASURES: Retrospective pre-post surveys on the efficiency, quality, and
      clarity of the patient interaction, written note, and verbal handoff, as well as
      open-ended comments. Respondents included night-float residents, day team
      residents, and attending physicians. KEY RESULTS: All night-float residents
      responded, reporting significant improvements in written note, verbal sign-out,
      assessment and plan, patient interaction, and overall efficiency (p < 0.05). Day
      team residents (n = 76) also reported increased clarity in verbal sign-out and
      written note, improved efficiency, and improved preparedness for presenting the
      patient (p < 0.05). Attending physician ratings did not differ between groups.
      CONCLUSIONS: Resident ratings indicate that the CPI can improve key aspects of
      patient care, including the patient interview, note, and physician-physician
      communication. These results suggest that the method should be taught and
      implemented more frequently.

PMID- 27896693
TI  - Capsule Commentary on Cheung et al., Leisure-Time Physical Activity and
      Cardiovascular Mortality in an Elderly Population in Northern Manhattan: A
      Prospective Cohort Study.

PMID- 27896694
TI  - Coronary Artery Embolism from Large Aortic Valve Vegetation due to Staphylococcus
      aureus Endocarditis.

PMID- 27896695
TI  - Seeing Wisely.

PMID- 27896692
TI  - Teaching Structure: A Qualitative Evaluation of a Structural Competency Training
      for Resident Physicians.
AB  - BACKGROUND: The influence of societal inequities on health has long been
      established, but such content has been incorporated unevenly into medical
      education and clinical training. Structural competency calls for medical
      education to highlight the important influence of social, political, and economic
      factors on health outcomes. AIM: This article describes the development,
      implementation, and evaluation of a structural competency training for medical
      residents. SETTING: A California family medicine residency program serving a
      patient population predominantly (88 %) with income below 200 % of the federal
      poverty level. PARTICIPANTS: A cohort of 12 residents in the family residency
      program. PROGRAM DESCRIPTION: The training was designed to help residents
      recognize and develop skills to respond to illness and health as the downstream
      effects of social, political, and economic structures. PROGRAM EVALUATION: The
      training was evaluated via qualitative analysis of surveys gathered immediately
      post-training (response rate 100 %) and a focus group 1 month post-training
      (attended by all residents not on service). DISCUSSION: Residents reported that
      the training had a positive impact on their clinical practice and relationships
      with patients. They also reported feeling overwhelmed by increased recognition of
      structural influences on patient health, and indicated a need for further
      training and support to address these influences.

PMID- 27896696
TI  - Editorial and Review: 31st ASMS Asilomar Conference on Native Mass Spectrometry
      Based Structural Biology.

PMID- 27896697
TI  - Metal Cationization Extractive Electrospray Ionization Mass Spectrometry of
      Compounds Containing Multiple Oxygens.
AB  - Extractive electrospray ionization is an ambient ionization technique that allows
      real-time sampling of liquid samples, including organic aerosols. Similar to
      electrospray ionization, the composition of the electrospray solvent used in
      extractive electrospray ionization can easily be altered to form metal cationized
      molecules during ionization simply by adding a metal salt to the electrospray
      solvent. An increase in sensitivity is observed for some molecules that are
      lithium, sodium, or silver cationized compared with the protonated molecule
      formed in extractive electrospray ionization with an acid additive. Tandem mass
      spectrometry of metal cationized molecules can also significantly improve the
      ability to identify a compound. Tandem mass spectrometry of lithium and silver
      cationized molecules can result in an increase in the number and uniqueness of
      dissociation pathways relative to [M + H]+. These results highlight the potential
      for extractive electrospray ionization with metal cationization in analyzing
      complex aerosol mixtures. Graphical Abstract ?.

PMID- 27896698
TI  - Atmospheric Pressure Ionization Using a High Voltage Target Compared to
      Electrospray Ionization.
AB  - A new atmospheric pressure ionization (API) source, viz. UniSpray, was evaluated
      for mass spectrometry (MS) analysis of pharmaceutical compounds by head-to-head
      comparison with electrospray ionization (ESI) on the same high-resolution MS
      system. The atmospheric pressure ionization source is composed of a grounded
      nebulizer spraying onto a high voltage, cylindrical stainless steel target.
      Molecules are ionized in a similar fashion to electrospray ionization,
      predominantly producing protonated or deprotonated species. Adduct formation
      (e.g., proton and sodium adducts) and in-source fragmentation is shown to be
      almost identical between the two sources. The performance of the new API source
      was compared with electrospray by infusion of a mix of 22 pharmaceutical
      compounds with a wide variety of functional groups and physico-chemical
      properties (molecular weight, logP, and pKa) in more than 100 different
      conditions (mobile phase strength, solvents, pH, and flow rate). The new API
      source shows an intensity gain of a factor 2.2 compared with ESI considering all
      conditions on all compounds tested. Finally, some hypotheses on the ionization
      mechanism, similarities, and differences with ESI, are discussed. Graphical
      Abstract ?.

PMID- 27896700
TI  - FAT4 functions as a tumor suppressor in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer
      that is often associated with biologic behavior with frequent distant metastasis.
      FAT tumor suppressor homolog 4 (FAT4), a cadherin-related protein, is involved in
      a variety of biological processes as a tumor suppressor; however, the role of
      FAT4 in TNBC is still unclear. The aim of our study was to identify the role of
      FAT4 in TNBC and examine the underlying molecular mechanisms. The expression of
      FAT4 was evaluated by immunohistochemistry, western blotting, and qRT-PCR in a
      series of TNBC tissues. The effects of FAT4 on the ability of cell proliferation,
      migration, and invasion were assessed by MTT assay and migration and invasion
      assays. We demonstrated that the repression of FAT4 by shRNA could promote TNBC
      progression. Taken together, our findings provide evidence for a role of the FAT4
      cluster as a tumor suppressor in TNBC patients and may serve as potential novel
      targets for the treatment of TNBC.

PMID- 27896701
TI  - I-123 metaiodobenzylguanidine innervation imaging as a tool for norepinephrine
      transporter research: A possible application for genetic analysis in heart
      failure.

PMID- 27896699
TI  - Cationized Carbohydrate Gas-Phase Fragmentation Chemistry.
AB  - We investigate the fragmentation chemistry of cationized carbohydrates using a
      combination of tandem mass spectrometry, regioselective labeling, and
      computational methods. Our model system is D-lactose. Barriers to the fundamental
      glyosidic bond cleavage reactions, neutral loss pathways, and structurally
      informative cross-ring cleavages are investigated. The most energetically
      favorable conformations of cationized D-lactose were found to be similar. In
      agreement with the literature, larger group I cations result in structures with
      increased cation coordination number which require greater collision energy to
      dissociate. In contrast with earlier proposals, the B n -Y m fragmentation
      pathways of both protonated and sodium-cationized analytes proceed via
      protonation of the glycosidic oxygen with concerted glycosidic bond cleavage.
      Additionally, for the sodiated congeners our calculations support sodiated 1,6
      anhydrogalactose B n ion structures, unlike the preceding literature. This
      affects the subsequent propensity of formation and prediction of B n /Y m
      branching ratio. The nature of the anomeric center (alpha/beta) affects the
      relative energies of these processes, but not the overall ranking. Low-energy
      cross-ring cleavages are observed for the metal-cationized analytes with a retro
      aldol mechanism producing the 0,2 A 2 ion from the sodiated forms. Theory and
      experiment support the importance of consecutive fragmentation processes,
      particularly for the protonated congeners at higher collision energies. Graphical
      Abstract ?.

PMID- 27896702
TI  - Safety of regadenoson stress testing in patients with pulmonary hypertension.
AB  - OBJECTIVES: We sought to determine the safety of regadenoson stress testing in
      patients with PH. BACKGROUND: PH is increasingly recognized at more advanced
      ages. As many as one-third of patients with PH have coronary artery disease.
      Because of their physical limitations, patients with PH are unable to adequately
      exercise. Regadenoson can potentially have an adverse impact due to their tenuous
      hemodynamics. Current guidelines suggest performing a coronary angiography in
      patients with PH who have angina or multiple coronary risk factors. METHODS: We
      identified 67 consecutive patients with confirmed PH by catheterization (mean PA
      > 25 mmHg not due to left heart disease) who underwent MPI with regadenoson
      stress. Medical records were reviewed to determine hemodynamic and ECG response
      to regadenoson. RESULTS: No serious events occurred. Common side effects related
      to regadenoson were observed, dyspnea being the most common (70.6%). No syncope
      occurred. Heart rate increased from 74.6 +/- 14 to 96.3 +/- 18.3 bpm, systolic
      blood pressure increased from 129.8 +/- 20.9 to 131.8 +/- 31 mmHg, and diastolic
      blood pressure decreased from 77.1 +/- 11.4 to 72.9 +/- 15.3 mmHg. There was no
      ventricular tachycardia, ventricular fibrillation, or second- or third-degree
      atrioventricular block. CONCLUSION: Regadenoson stress MPI appears to be well
      tolerated and safe in patients with PH.

PMID- 27896704
TI  - External and internal compressions to retrieve a kinked catheter in the right
      brachial artery.
AB  - Kinking of the catheter due to excessive rotation is not a rare complication.
      However, percutaneous retrieval of a kinked catheter can be difficult. The key to
      bailout is fixation of the catheter tip. Herein, we present a 78-year-old woman
      who had this complication during transradial angiography. Retrieval using several
      previously reported techniques was unsuccessful. We finally retrieved the kinked
      catheter by fixing the tip of the catheter, using external and internal
      compressions. The former comprises manual compression on the axillary artery,
      while the latter comprises deployment of a balloon catheter via another puncture
      site.

PMID- 27896703
TI  - Spreading activation in nonverbal memory networks.
AB  - Theories of spreading activation primarily involve semantic memory networks.
      However, the existence of separate verbal and visuospatial memory networks
      suggests that spreading activation may also occur in visuospatial memory
      networks. The purpose of the present investigation was to explore this
      possibility. Specifically, this study sought to create and describe the design
      frequency corpus and to determine whether this measure of visuospatial spreading
      activation was related to right hemisphere functioning and spreading activation
      in verbal memory networks. We used word frequencies taken from the Controlled
      Oral Word Association Test and design frequencies taken from the Ruff Figural
      Fluency Test as measures of verbal and visuospatial spreading activation,
      respectively. Average word and design frequencies were then correlated with
      measures of left and right cerebral functioning. The results indicated that a
      significant relationship exists between performance on a test of right posterior
      functioning (Block Design) and design frequency. A significant negative
      relationship also exists between spreading activation in semantic memory networks
      and design frequency. Based on our findings, the hypotheses were supported.
      Further research will need to be conducted to examine whether spreading
      activation exists in visuospatial memory networks as well as the parameters that
      might modulate this spreading activation, such as the influence of
      neurotransmitters.

PMID- 27896705
TI  - Does Gender Influence the Cardiovascular Benefits Observed with Sodium Glucose Co
      Transporter-2 (SGLT-2) Inhibitors? A Meta-Regression Analysis.
AB  - INTRODUCTION: Although a large recent trial had shown improved cardiovascular
      outcomes of diabetic patients on sodium glucose co-transporter-2 (SGLT-2)
      inhibitors, the influence of gender differences on such outcomes is not known.
      Thus, we aimed to assess the impact of gender on such outcomes in the patients
      with type 2 diabetes mellitus receiving SGLT-2 inhibitors. METHODS: A search of
      electronic databases was conducted for all randomized trials comparing SGLT-2
      inhibitors with placebo in patients with diabetes mellitus. Primary outcomes were
      all-cause mortality and cardiovascular mortality. Random effects meta-regression
      was conducted using the percentage of women included in the SGLT-2 inhibitor arm
      of each trial with a P value of <0.1 for statistical significance. RESULTS: A
      total of 22,256 patients from 26 trials were included. The overall odds ratio
      (OR) of all-cause mortality [OR = 0.72, 95% confidence interval (CI) 0.60-0.86, P
      < 0.001, I 2 = 0%], and cardiovascular mortality (OR = 0.67, 95% CI 0.53-0.84, P
      = 0.001, I 2 = 23%) were lower with SGLT-2 inhibitors. Meta-regression suggested
      a possible incremental increase in the OR for all-cause mortality and
      cardiovascular mortality as the percentage of women in the SGLT-2 inhibitor arm
      increased (P = 0.07 and 0.08, respectively). CONCLUSION: Gender might influence
      the cardiovascular benefits observed with SGLT-2 inhibitors in patients with type
      2 diabetes mellitus.

PMID- 27896707
TI  - Detection costs and contingent attentional capture.
AB  - Peripheral cues reduce reaction times (RTs) to targets at the cued location with
      short cue-target SOAs (cueing benefits) but increase RTs at long SOAs (cueing
      costs or inhibition of return). In detection tasks, cueing costs occur at shorter
      SOAs and are larger compared with identification tasks. To account for effects of
      task, detection cost theory claims that the integration of cue and target into an
      object file makes it more difficult to detect the target as a new event, which is
      the principal task-requirement in detection tasks. The integration of cue and
      target is expected to increase when cue and target are similar. We provided
      evidence for detection cost theory in the modified spatial cueing paradigm. Two
      types of cues (onset, color) were paired with two types of targets (onset, color)
      in separate blocks of trials. In the identification task, we found cueing
      benefits with matching (i.e., similar) cue-target pairs (onset-onset, color
      color) and no cueing effects with nonmatching cue-target pairs (onset-color,
      color-onset), which replicates previous work. In the detection task, cueing
      effects with matching cues were reduced and even turned into cueing costs for
      onset cues with onset targets, suggesting that cue-target integration made it
      more difficult to detect targets at the cued location as new events. In contrast,
      the results for nonmatching cue-target pairs were not affected by task.
      Furthermore, the pattern of false alarms in the detection task provides a measure
      of similarity that may explain the size of cueing benefits and costs.

PMID- 27896708
TI  - Asymmetric interference in concurrent time-to-contact estimation: Cousin or twin
      of the psychological refractory period effect?
AB  - In a reaction time (RT) task requiring fast responses to two stimuli presented
      close in time, human observers show a delayed RT to the second stimulus. This
      phenomenon has been attributed to a psychological refractory period (PRP). A
      similar asymmetric interference is found when performing multiple concurrent
      visual time-to-contact (TTC) estimations for moving objects, despite important
      differences between the tasks. In the present study, we studied the properties of
      the asymmetric interference found in the TTC task and compared them to the
      classical PRP effect. In Experiment 1, we varied the time interval between the
      two objects' arrival times to determine the dependence of the PRP-like effect on
      the asynchrony between the two TTCs. In Experiment 2, we investigated whether the
      physical or the perceived arrival order determined the asymmetric interference.
      Our results confirmed the existence of asymmetric interference in the multiple
      TTC estimation task, but also indicated important differences from the
      traditional PRP effect observed in the RT paradigm. The origins of these
      differences are discussed, as well as the practical implications.

PMID- 27896706
TI  - Anesthetics and Outcome in Status Epilepticus: A Matched Two-Center Cohort Study.
AB  - BACKGROUND: The use of anesthetics has been linked to poor outcome in patients
      with status epilepticus (SE). This association, however, may be confounded, as
      anesthetics are mostly administered in patients with more severe SE and critical
      illnesses. OBJECTIVE: To minimize treatment-selection bias, we assessed the
      association between continuously administered intravenous anesthetic drugs
      (IVADs) and outcome in SE patients by a matched two-center study design. METHODS:
      This cohort study was performed at the Johns Hopkins Bayview Medical Center,
      Baltimore, MD, USA and the University Hospital Basel, Basel, Switzerland. All
      consecutive adult SE patients from 2005 to 2013 were included. Odds ratios (ORs)
      for death and unfavorable outcome (Glasgow Outcome Score [GOS] 1-3) associated
      with administration of IVADs were calculated. To account for confounding by known
      outcome determinants (age, level of consciousness, worst seizure type,
      acute/fatal etiology, mechanical ventilation, and SE duration), propensity score
      matching and coarsened exact matching were performed in addition to multivariable
      regression models. RESULTS: Among 406 consecutive patients, 139 (34.2%) were
      treated with IVADs. Logistic regression analyses of the unmatched and matched
      cohorts revealed increased odds for death and unfavorable outcome in survivors
      who had received IVADs (unmatched: ORdeath = 3.13, 95% confidence interval [CI]
      1.47-6.60 and ORGOS1-3 = 2.51, 95% CI 1.37-4.60; propensity score matched:
      ORdeath = 3.29, 95% CI 1.35-8.05 and ORGOS1-3 = 2.27, 95% CI 1.02-5.06; coarsened
      exact matched: ORdeath = 2.19, 95% CI 1.27-3.78 and ORGOS1-3 = 3.94, 95% CI 2.12
      7.32). CONCLUSION: The use of IVADs in SE is associated with death and
      unfavorable outcome in survivors independent of known confounders and using
      different statistical approaches. Randomized trials are needed to determine if
      these associations are biased by outcome predictors not yet identified and hence
      not accounted for in this study.

PMID- 27896709
TI  - Learned value and object perception: Accelerated perception or biased decisions?
AB  - Learned value is known to bias visual search toward valued stimuli. However, some
      uncertainty exists regarding the stage of visual processing that is modulated by
      learned value. Here, we directly tested the effect of learned value on
      preattentive processing using temporal order judgments. Across four experiments,
      we imbued some stimuli with high value and some with low value, using a
      nonmonetary reward task. In Experiment 1, we replicated the value-driven
      distraction effect, validating our nonmonetary reward task. Experiment 2 showed
      that high-value stimuli, but not low-value stimuli, exhibit a prior-entry effect.
      Experiment 3, which reversed the temporal order judgment task (i.e., reporting
      which stimulus came second), showed no prior-entry effect, indicating that
      although a response bias may be present for high-value stimuli, they are still
      reported as appearing earlier. However, Experiment 4, using a simultaneity
      judgment task, showed no shift in temporal perception. Overall, our results
      support the conclusion that learned value biases perceptual decisions about
      valued stimuli without speeding preattentive stimulus processing.

PMID- 27896710
TI  - How social network heterogeneity facilitates lexical access and lexical
      prediction.
AB  - People learn language from their social environment. As individuals differ in
      their social networks, they might be exposed to input with different lexical
      distributions, and these might influence their linguistic representations and
      lexical choices. In this article we test the relation between linguistic
      performance and 3 social network properties that should influence input
      variability, namely, network size, network heterogeneity, and network density. In
      particular, we examine how these social network properties influence lexical
      prediction, lexical access, and lexical use. To do so, in Study 1, participants
      predicted how people of different ages would name pictures, and in Study 2
      participants named the pictures themselves. In both studies, we examined how
      participants' social network properties related to their performance. In Study 3,
      we ran simulations on norms we collected to see how age variability in one's
      network influences the distribution of different names in the input. In all
      studies, network age heterogeneity influenced performance leading to better
      prediction, faster response times for difficult-to-name items, and less entropy
      in input distribution. These results suggest that individual differences in
      social network properties can influence linguistic behavior. Specifically, they
      show that having a more heterogeneous network is associated with better
      performance. These results also show that the same factors influence lexical
      prediction and lexical production, suggesting the two might be related.

PMID- 27896712
TI  - Applications of Accelerators and Radiation Sources in the Field of Space Research
      and Industry.
AB  - Beyond their important economic role in commercial communications, satellites in
      general are critical infrastructure because of the services they provide. In
      addition to satellites providing information which facilitates a better
      understanding of the space environment and improved performance of physics
      experiments, satellite observations are also used to actively monitor weather,
      geological processes, agricultural development and the evolution of natural and
      man-made hazards. Defence agencies depend on satellite services for communication
      in remote locations, as well as for reconnaissance and intelligence. Both
      commercial and government users rely on communication satellites to provide
      communication in the event of a disaster that damages ground-based communication
      systems, provide news, education and entertainment to remote areas and connect
      global businesses. The space radiation environment is an hazard to most satellite
      missions and can lead to extremely difficult operating conditions for all of the
      equipment travelling in space. Here, we first provide an overview of the main
      components of space radiation environment, followed by a description of the basic
      mechanism of the interaction of radiation with matter. This is followed by an
      introduction to the space radiation hardness assurance problem and the main
      effects of natural radiation to the microelectronics (total ionizing dose,
      displacement damage and the single-event effect and a description of how
      different effects occurring in the space can be tested in on-ground experiments
      by using particle accelerators and radiation sources. We also discuss standards
      and the recommended procedures to obtain reliable results.

PMID- 27896711
TI  - Using EQ-5D-3L and OAB-5D to assess changes in the health-related quality of life
      of men with lower urinary tract symptoms associated with benign prostatic
      hyperplasia.
AB  - OBJECTIVES: To assess changes in the health status of men with lower urinary
      tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) using the
      EQ-5D-3L and OAB-5D instruments and to evaluate the sensitivity of the
      instruments. METHODS: Data were available from a large randomised phase III trial
      of men with moderate-to-severe storage and voiding LUTS/BPH (NEPTUNE). Men
      received a fixed-dose combination of solifenacin 6 mg plus oral controlled
      absorption system (OCASTM) formulation of tamsulosin (TOCAS, 0.4 mg), TOCAS
      monotherapy or placebo and completed the EQ-5D-3L and OAB-5D at baseline and
      weeks 4, 8 and 12. Analysis of covariance was used to estimate changes in EQ-5D
      3L Index, EQ-VAS and OAB-5D. Changes in dimension level were summarised using the
      Paretian Classification of Health Change (PCHC). RESULTS: Improved health-related
      quality of life from baseline was seen in all treatment arms on EQ-5D-3L and OAB
      5D at week 12, although only OAB-5D showed statistically significant differences
      between active treatment and placebo, both on the index score and using the PCHC
      approach. Effect sizes in the active treatment groups were large (>0.8) on OAB-5D
      but small (~0.2) on EQ-5D-3L. EQ-5D-3L showed a very high ceiling effect (45% of
      men reported full health at baseline) and a substantial proportion of these men
      reported improvements at week 12 in several dimensions of OAB-5D. CONCLUSIONS: A
      large ceiling effect on EQ-5D-3L substantially limited its sensitivity in this
      population. OAB-5D proved more sensitive to changes in health status and could be
      considered a complement to ED-5D-3L as a source of utilities for health economic
      modelling.

PMID- 27896713
TI  - Resistance to Cultural Intervention: Formation of Inhibitory Collective and
      children's Self-Defensive Regulation in a Chinese School.
AB  - A sequel to the previous article "Roots of Excellence: The Releasing Effect of
      Individual Potentials through Educational Cultural Intervention in a Chinese
      School" (in press), the present study is on the unexpected reversal phenomena in
      the process of cultural intervention. The goal of the intervention is to
      construct the dynamics of Jiti (well-organized collective in Chinese) through
      creative activities to promote students' development. In the intervention, the
      releasing effect (Wu et al. 2016) emerged as well, but the teacher's concern
      about worsening discipline and academic performance evoked and reinforced his
      habitual notions and practices of education, turning the joint activities into a
      way of strengthening discipline. The energy that had been discharging at the
      beginning of the intervention was inhibited, so that many more problematic
      behaviors took shape. The whole class formed an inhibitory atmosphere, within
      which pupils formed self-defensive regulation strategies. By comparing with the
      productive collective in which intervention was effective and analyzing this
      unexpected reversal process, we can not only see pupils' self-construction status
      in the inhibitory culture but illuminate the formation of the teacher's
      resistance to educational and cultural transformation as well. Resistance is
      originated from teachers not being able to interpret pupils' inner developmental
      needs but instead anxious about the ongoing problems.

PMID- 27896715
TI  - Genome Sequencing.
AB  - Genome sequencing is an important step toward correlating genotypes with
      phenotypic characters. Sequencing technologies are important in many fields in
      the life sciences, including functional genomics, transcriptomics, oncology,
      evolutionary biology, forensic sciences, and many more. The era of sequencing has
      been divided into three generations. First generation sequencing involved
      sequencing by synthesis (Sanger sequencing) and sequencing by cleavage (Maxam
      Gilbert sequencing). Sanger sequencing led to the completion of various genome
      sequences (including human) and provided the foundation for development of other
      sequencing technologies. Since then, various techniques have been developed which
      can overcome some of the limitations of Sanger sequencing. These techniques are
      collectively known as "Next-generation sequencing" (NGS), and are further
      classified into second and third generation technologies. Although NGS methods
      have many advantages in terms of speed, cost, and parallelism, the accuracy and
      read length of Sanger sequencing is still superior and has confined the use of
      NGS mainly to resequencing genomes. Consequently, there is a continuing need to
      develop improved real time sequencing techniques. This chapter reviews some of
      the options currently available and provides a generic workflow for sequencing a
      genome.

PMID- 27896716
TI  - Sequence Assembly.
AB  - We describe an efficient method for assembling short reads into long sequences.
      In this method, a hashing technique is used to compute overlaps between short
      reads, allowing base mismatches in the overlaps. Then an overlap graph is
      constructed, with each vertex representing a read and each edge representing an
      overlap. The overlap graph is explored by graph algorithms to find unique paths
      of reads representing contigs. The consensus sequence of each contig is
      constructed by computing alignments of multiple reads without gaps. This strategy
      has been implemented as a short read assembly program called PCAP.Solexa. We also
      describe how to use PCAP. Solexa in assembly of short reads.

PMID- 27896717
TI  - A Practical Approach to Protein Crystallography.
AB  - Macromolecular crystallography is a powerful tool for structural biology. The
      resolution of a protein crystal structure is becoming much easier than in the
      past, thanks to developments in computing, automation of crystallization
      techniques and high-flux synchrotron sources to collect diffraction datasets. The
      aim of this chapter is to provide practical procedures to determine a protein
      crystal structure, illustrating the new techniques, experimental methods, and
      software that have made protein crystallography a tool accessible to a larger
      scientific community.It is impossible to give more than a taste of what the X-ray
      crystallographic technique entails in one brief chapter and there are different
      ways to solve a protein structure. Since the number of structures available in
      the Protein Data Bank (PDB) is becoming ever larger (the protein data bank now
      contains more than 100,000 entries) and therefore the probability to find a good
      model to solve the structure is ever increasing, we focus our attention on the
      Molecular Replacement method. Indeed, whenever applicable, this method allows the
      resolution of macromolecular structures starting from a single data set and a
      search model downloaded from the PDB, with the aid only of computer work.

PMID- 27896714
TI  - Stopping ability in younger and older adults: Behavioral and event-related
      potential.
AB  - This study examines age-related differences in inhibitory control as measured by
      stop-signal performance. The participants were 24 adults aged 20-30 years and 24
      older adults aged 61-76 years. The task blocks were pure choice reaction-time
      blocks, global stop-signal blocks (with an auditory stop signal), and selective
      stop-signal blocks (with valid and invalid stop signals). There was a decline in
      reactive inhibitory control for the older group reflected by greater stop-signal
      reaction times and reduced P3 peak amplitudes in both global and selective stop
      signal task blocks. The decreased reactive inhibitory control might result from
      speed-accuracy tradeoffs. Conversely, no age-related decline in proactive
      inhibitory control was observed. This was reflected by slower response times
      (RTs) and reduced P3 peak amplitudes during GO trials in blocks with stop-signals
      relative to those in blocks of pure choice reaction-time tasks, and in which the
      RT and amplitude differences were similar between groups. The results further
      show age-related compensation responses associated with proactive inhibition,
      such as increased activation at the frontal site among older participants,
      resulting in no differences in P3 peak amplitudes between electrode sites, and
      smaller differences at the Fz site than other sites compared with younger adults.
      For older adults, the P3 peak amplitude at the Fz site was significantly
      correlated with the RT of proactive inhibitory control. This shows that larger RT
      differences were associated with larger reductions in P3 peak amplitudes in the
      stop-signal blocks relative to the pure choice blocks. These results appear to
      support age-related compensation hypotheses.

PMID- 27896718
TI  - Managing Sequence Data.
AB  - Nucleotide and protein sequences are the foundation for all bioinformatics tools
      and resources. Researchers can analyze these sequences to discover genes or
      predict the function of their products. The INSDC (International Nucleotide
      Sequence Database-DDBJ/ENA/GenBank + SRA) is an international, centralized
      primary sequence resource that is freely available on the Internet. This database
      contains all publicly available nucleotide and derived protein sequences. This
      chapter discusses the structure and history of the nucleotide sequence database
      resources built at NCBI, provides information on how to submit sequences to the
      databases, and explains how to access the sequence data.

PMID- 27896719
TI  - Genome Annotation.
AB  - The dynamic structure and functions of genomes are being revealed simultaneously
      with the progress of technologies and researches in genomics. Evidence indicating
      genome regional characteristics (genome annotations in a broad sense) provide the
      basis for further analyses. Target listing and screening can be effectively
      performed in silico using such data. Here, we describe steps to obtain publicly
      available genome annotations or to construct new annotations based on your own
      analyses, as well as an overview of the types of available genome annotations and
      corresponding resources.

PMID- 27896720
TI  - Working with Ontologies.
AB  - Ontologies are powerful and popular tools to encode data in a structured format
      and manage knowledge. A large variety of existing ontologies offer users access
      to biomedical knowledge. This chapter contains a short theoretical background of
      ontologies and introduces two notable examples: The Gene Ontology and the
      ontology for Biological Pathways Exchange. For both ontologies a short overview
      and working bioinformatic applications, i.e., Gene Ontology enrichment analyses
      and pathway data visualization, are provided.

PMID- 27896721
TI  - The Classification of Protein Domains.
AB  - The significant expansion in protein sequence and structure data that we are now
      witnessing brings with it a pressing need to bring order to the protein world.
      Such order enables us to gain insights into the evolution of proteins, their
      function and the extent to which the functional repertoire can vary across the
      three kingdoms of life. This has lead to the creation of a wide range of protein
      family classifications that aim to group proteins based upon their evolutionary
      relationships.In this chapter we discuss the approaches and methods that are
      frequently used in the classification of proteins, with a specific emphasis on
      the classification of protein domains. The construction of both domain sequence
      and domain structure databases is considered and we show how the use of domain
      family annotations to assign structural and functional information is enhancing
      our understanding of genomes.

PMID- 27896722
TI  - Multiple Sequence Alignment.
AB  - The increasing importance of Next Generation Sequencing (NGS) techniques has
      highlighted the key role of multiple sequence alignment (MSA) in comparative
      structure and function analysis of biological sequences. MSA often leads to
      fundamental biological insight into sequence-structure-function relationships of
      nucleotide or protein sequence families. Significant advances have been achieved
      in this field, and many useful tools have been developed for constructing
      alignments, although many biological and methodological issues are still open.
      This chapter first provides some background information and considerations
      associated with MSA techniques, concentrating on the alignment of protein
      sequences. Then, a practical overview of currently available methods and a
      description of their specific advantages and limitations are given, to serve as a
      helpful guide or starting point for researchers who aim to construct a reliable
      MSA.

PMID- 27896724
TI  - Genomic Database Searching.
AB  - The availability of reference genome sequences for virtually all species under
      active research has revolutionized biology. Analyses of genomic variations in
      many organisms have provided insights into phenotypic traits, evolution and
      disease, and are transforming medicine. All genomic data from publicly funded
      projects are freely available in Internet-based databases, for download or
      searching via genome browsers such as Ensembl, Vega, NCBI's Map Viewer, and the
      UCSC Genome Browser. These online tools generate interactive graphical outputs of
      relevant chromosomal regions, showing genes, transcripts, and other genomic
      landmarks, and epigenetic features mapped by projects such as ENCODE.This chapter
      provides a broad overview of the major genomic databases and browsers, and
      describes various approaches and the latest resources for searching them. Methods
      are provided for identifying genomic locus and sequence information using gene
      names or codes, identifiers for DNA and RNA molecules and proteins; also from
      karyotype bands, chromosomal coordinates, sequences, motifs, and matrix-based
      patterns. Approaches are also described for batch retrieval of genomic
      information, performing more complex queries, and analyzing larger sets of
      experimental data, for example from next-generation sequencing projects.

PMID- 27896723
TI  - Large-Scale Sequence Comparison.
AB  - There are millions of sequences deposited in genomic databases, and it is an
      important task to categorize them according to their structural and functional
      roles. Sequence comparison is a prerequisite for proper categorization of both
      DNA and protein sequences, and helps in assigning a putative or hypothetical
      structure and function to a given sequence. There are various methods available
      for comparing sequences, alignment being first and foremost for sequences with a
      small number of base pairs as well as for large-scale genome comparison. Various
      tools are available for performing pairwise large sequence comparison. The best
      known tools either perform global alignment or generate local alignments between
      the two sequences. In this chapter we first provide basic information regarding
      sequence comparison. This is followed by the description of the PAM and BLOSUM
      matrices that form the basis of sequence comparison. We also give a practical
      overview of currently available methods such as BLAST and FASTA, followed by a
      description and overview of tools available for genome comparison including
      LAGAN, MumMER, BLASTZ, and AVID.

PMID- 27896725
TI  - Finding Genes in Genome Sequence.
AB  - Gene finding is the process of identifying genome sequence regions representing
      stretches of DNA that encode biologically active products, such as proteins or
      functional noncoding RNAs. As this is usually the first step in the analysis of
      any novel genomic sequence or resequenced sample of well-known organisms, it is a
      very important issue, as all downstream analyses depend on the results. This
      chapter describes the biological basis for gene finding, and the programs and
      computational approaches that are available for the automated identification of
      protein-coding genes. For bacterial, archaeal, and eukaryotic genomes, as well as
      for multi-species sequence data originating from environmental community studies,
      the state of the art in automated gene finding is described.

PMID- 27896726
TI  - Sequence Segmentation with changeptGUI.
AB  - Many biological sequences have a segmental structure that can provide valuable
      clues to their content, structure, and function. The program changept is a tool
      for investigating the segmental structure of a sequence, and can also be applied
      to multiple sequences in parallel to identify a common segmental structure, thus
      providing a method for integrating multiple data types to identify functional
      elements in genomes. In the previous edition of this book, a command line
      interface for changept is described. Here we present a graphical user interface
      for this package, called changeptGUI. This interface also includes tools for pre-
      and post-processing of data and results to facilitate investigation of the number
      and characteristics of segment classes.

PMID- 27896727
TI  - Measuring Natural Selection.
AB  - In this chapter, I review the basic algorithm underlying the CODEML model
      implemented in the software package PAML. This is intended as a companion to the
      software's manual, and a primer to the extensive literature available on CODEML.
      At the end of this chapter, I hope that you will be able to understand enough of
      how CODEML operates to plan your own analyses.

PMID- 27896729
TI  - Identifying Optimal Models of Evolution.
AB  - Most phylogenetic methods are model-based and depend on models of evolution
      designed to approximate the evolutionary processes. Several methods have been
      developed to identify suitable models of evolution for phylogenetic analysis of
      alignments of nucleotide or amino acid sequences and some of these methods are
      now firmly embedded in the phylogenetic protocol. However, in a disturbingly
      large number of cases, it appears that these models were used without
      acknowledgement of their inherent shortcomings. In this chapter, we discuss the
      problem of model selection and show how some of the inherent shortcomings may be
      identified and overcome.

PMID- 27896728
TI  - Inferring Trees.
AB  - Molecular evolution can reveal the relationship between sets of homologous
      sequences and the patterns of change that occur during their evolution. An
      important aspect of these studies is the inference of a phylogenetic tree, which
      explicitly describes evolutionary relationships between homologous sequences.
      This chapter provides an introduction to evolutionary trees and how to infer them
      from sequence data using some commonly used inferential methodology. It focuses
      on statistical methods for inferring trees and how to assess the confidence one
      should have in any resulting tree, with a particular emphasis on the underlying
      assumptions of the methods and how they might affect the tree estimate. There is
      also some discussion of the underlying algorithms used to perform tree search and
      recommendations regarding the performance of different algorithms. Finally, there
      are a few practical guidelines, including how to combine multiple software
      packages to improve inference, and a comparison between Bayesian and Maximum
      likelihood phylogenetics.

PMID- 27896730
TI  - Scaling Up the Phylogenetic Detection of Lateral Gene Transfer Events.
AB  - Lateral genetic transfer (LGT) is the process by which genetic material moves
      between organisms (and viruses) in the biosphere. Among the many approaches
      developed for the inference of LGT events from DNA sequence data, methods based
      on the comparison of phylogenetic trees remain the gold standard for many types
      of problem. Identifying LGT events from sequenced genomes typically involves a
      series of steps in which homologous sequences are identified and aligned,
      phylogenetic trees are inferred, and their topologies are compared to identify
      unexpected or conflicting relationships. These types of approach have been used
      to elucidate the nature and extent of LGT and its physiological and ecological
      consequences throughout the Tree of Life. Advances in DNA sequencing technology
      have led to enormous increases in the number of sequenced genomes, including
      ultra-deep sampling of specific taxonomic groups and single cell-based sequencing
      of unculturable "microbial dark matter." Environmental shotgun sequencing enables
      the study of LGT among organisms that share the same habitat.This abundance of
      genomic data offers new opportunities for scientific discovery, but poses two key
      problems. As ever more genomes are generated, the assembly and annotation of each
      individual genome receives less scrutiny; and with so many genomes available it
      is tempting to include them all in a single analysis, but thousands of genomes
      and millions of genes can overwhelm key algorithms in the analysis pipeline.
      Identifying LGT events of interest therefore depends on choosing the right
      dataset, and on algorithms that appropriately balance speed and accuracy given
      the size and composition of the chosen set of genomes.

PMID- 27896731
TI  - Detecting and Analyzing Genetic Recombination Using RDP4.
AB  - Recombination between nucleotide sequences is a major process influencing the
      evolution of most species on Earth. The evolutionary value of recombination has
      been widely debated and so too has its influence on evolutionary analysis methods
      that assume nucleotide sequences replicate without recombining. When nucleic
      acids recombine, the evolution of the daughter or recombinant molecule cannot be
      accurately described by a single phylogeny. This simple fact can seriously
      undermine the accuracy of any phylogenetics-based analytical approach which
      assumes that the evolutionary history of a set of recombining sequences can be
      adequately described by a single phylogenetic tree. There are presently a large
      number of available methods and associated computer programs for analyzing and
      characterizing recombination in various classes of nucleotide sequence datasets.
      Here we examine the use of some of these methods to derive and test recombination
      hypotheses using multiple sequence alignments.

PMID- 27896732
TI  - Species Tree Estimation from Genome-Wide Data with guenomu.
AB  - The history of particular genes and that of the species that carry them can be
      different for a variety of reasons. In particular, gene trees and species trees
      can differ due to well-known evolutionary processes such as gene duplication and
      loss, lateral gene transfer, or incomplete lineage sorting. Species tree
      reconstruction methods have been developed to take this incongruence into
      account; these can be divided grossly into supertree and supermatrix approaches.
      Here we introduce a new Bayesian hierarchical model that we have recently
      developed and implemented in the program guenomu. The new model considers
      multiple sources of gene tree/species tree disagreement. Guenomu takes as input
      posterior distributions of unrooted gene tree topologies for multiple gene
      families, in order to estimate the posterior distribution of rooted species tree
      topologies.

PMID- 27896733
TI  - 3D Computational Modeling of Proteins Using Sparse Paramagnetic NMR Data.
AB  - Computational modeling of proteins using evolutionary or de novo approaches
      offers rapid structural characterization, but often suffers from low success
      rates in generating high quality models comparable to the accuracy of structures
      observed in X-ray crystallography or nuclear magnetic resonance (NMR)
      spectroscopy. A computational/experimental hybrid approach incorporating sparse
      experimental restraints in computational modeling algorithms drastically improves
      reliability and accuracy of 3D models. This chapter discusses the use of
      structural information obtained from various paramagnetic NMR measurements and
      demonstrates computational algorithms implementing pseudocontact shifts as
      restraints to determine the structure of proteins at atomic resolution.

PMID- 27896734
TI  - Inferring Function from Homology.
AB  - Recent technological advances in sequencing and high-throughput DNA cloning have
      resulted in the generation of vast quantities of biological sequence data.
      Ideally the functions of individual genes and proteins predicted by these methods
      should be assessed experimentally within the context of a defined hypothesis.
      However, if no hypothesis is known a priori, or the number of sequences to be
      assessed is large, bioinformatics techniques may be useful in predicting
      function.This chapter proposes a pipeline of freely available Web-based tools to
      analyze protein-coding DNA and peptide sequences of unknown function. Accumulated
      information obtained during each step of the pipeline is used to build a testable
      hypothesis of function.The following methods are described in detail: 1.
      Annotation of gene function through Protein domain detection (SMART and Pfam). 2.
      Sequence similarity methods for homolog detection (BLAST and DELTA-BLAST). 3.
      Comparing sequences to whole genome data.

PMID- 27896735
TI  - Inferring Functional Relationships from Conservation of Gene Order.
AB  - Predicting functional associations using the Gene Neighbor Method depends on the
      simple idea that if genes are conserved next to each other in evolutionarily
      distant prokaryotes they might belong to a polycistronic transcription unit. The
      procedure presented in this chapter starts with the organization of the genes
      within genomes into pairs of adjacent genes. Then, the pairs of adjacent genes in
      a genome of interest are mapped to their corresponding orthologs in other,
      informative, genomes. The final step is to verify if the mapped orthologs are
      also pairs of adjacent genes in the informative genomes.

PMID- 27896736
TI  - Structural and Functional Annotation of Long Noncoding RNAs.
AB  - Protein-coding RNAs represent only a small fraction of the transcriptional output
      in higher eukaryotes. The remaining RNA species encompass a broad range of
      molecular functions and regulatory roles, a consequence of the structural
      polyvalence of RNA polymers. Albeit several classes of small noncoding RNAs are
      relatively well characterized, the accessibility of affordable high-throughput
      sequencing is generating a wealth of novel, unannotated transcripts, especially
      long noncoding RNAs (lncRNAs) that are derived from genomic regions that are
      antisense, intronic, intergenic, and overlapping protein-coding loci. Parsing and
      characterizing the functions of noncoding RNAs-lncRNAs in particular-is one of
      the great challenges of modern genome biology. Here we discuss concepts and
      computational methods for the identification of structural domains in lncRNAs
      from genomic and transcriptomic data. In the first part, we briefly review how to
      identify RNA structural motifs in individual lncRNAs. In the second part, we
      describe how to leverage the evolutionary dynamics of structured RNAs in a
      computationally efficient screen to detect putative functional lncRNA motifs
      using comparative genomics.

PMID- 27896737
TI  - Construction of Functional Gene Networks Using Phylogenetic Profiles.
AB  - Functional constraints between genes display similar patterns of gain or loss
      during speciation. Similar phylogenetic profiles, therefore, can be an indication
      of a functional association between genes. The phylogenetic profiling method has
      been applied successfully to the reconstruction of gene pathways and the
      inference of unknown gene functions. This method requires only sequence data to
      generate phylogenetic profiles. This method therefore has the potential to take
      advantage of the recent explosion in available sequence data to reveal a
      significant number of functional associations between genes. Since the initial
      development of phylogenetic profiling, many modifications to improve this method
      have been proposed, including improvements in the measurement of profile
      similarity and the selection of reference species. Here, we describe the existing
      methods of phylogenetic profiling for the inference of functional associations
      and discuss their technical limitations and caveats.

PMID- 27896738
TI  - Inferring Genome-Wide Interaction Networks.
AB  - The inference of gene regulatory networks is an important process that
      contributes to a better understanding of biological and biomedical problems.
      These networks aim to capture the causal molecular interactions of biological
      processes and provide valuable information about normal cell physiology. In this
      book chapter, we introduce GNI methods, namely C3NET, RN, ARACNE, CLR, and MRNET
      and describe their components and working mechanisms. We present a comparison of
      the performance of these algorithms using the results of our previously published
      studies. According to the study results, which were obtained from simulated as
      well as expression data sets, the inference algorithm C3NET provides consistently
      better results than the other widely used methods.

PMID- 27896739
TI  - Integrating Heterogeneous Datasets for Cancer Module Identification.
AB  - The availability of multiple heterogeneous high-throughput datasets provides an
      enabling resource for cancer systems biology. Types of data include: Gene
      expression (GE), copy number aberration (CNA), miRNA expression, methylation, and
      protein-protein Interactions (PPI). One important problem that can potentially be
      solved using such data is to determine which of the possible pair-wise
      interactions among genes contributes to a range of cancer-related events, from
      tumorigenesis to metastasis. It has been shown by various studies that applying
      integrated knowledge from multi-omics datasets elucidates such complex phenomena
      with higher statistical significance than using a single type of dataset
      individually. However, computational methods for processing multiple data types
      simultaneously are needed. This chapter reviews some of the computational methods
      that use integrated approaches to find cancer-related modules.

PMID- 27896740
TI  - Metabolic Pathway Mining.
AB  - Understanding metabolic pathways is one of the most important fields in
      bioscience in the post-genomic era, but curating metabolic pathways requires
      considerable man-power. As such there is a lack of reliable, experimentally
      verified metabolic pathways in databases and databases are forced to predict all
      but the most immediately useful pathways.Text-mining has the potential to solve
      this problem, but while sophisticated text-mining methods have been developed to
      assist the curation of many types of biomedical networks, such as protein-protein
      interaction networks, the mining of metabolic pathways from the literature has
      been largely neglected by the text-mining community. In this chapter we describe
      a pipeline for the extraction of metabolic pathways built on freely available
      open-source components and a heuristic metabolic reaction extraction algorithm.

PMID- 27896741
TI  - Analysis of Genome-Wide Association Data.
AB  - The last decade has seen substantial advances in the understanding of the
      genetics of complex traits and disease. This has been largely driven by genome
      wide association studies (GWAS), which have identified thousands of genetic loci
      associated with these traits and disease. This chapter provides a guide on how to
      perform GWAS on both binary (case-control) and quantitative traits. As poor data
      quality, through both genotyping failures and unobserved population structure, is
      a major cause of false-positive genetic associations, there is a particular focus
      on the crucial steps required to prepare the SNP data prior to analysis. This is
      followed by the methods used to perform the actual GWAS and visualization of the
      results.

PMID- 27896742
TI  - Adjusting for Familial Relatedness in the Analysis of GWAS Data.
AB  - Relatedness within a sample can be of ancient (population stratification) or
      recent (familial structure) origin, and can either be known (pedigree data) or
      unknown (cryptic relatedness). All of these forms of familial relatedness have
      the potential to confound the results of genome-wide association studies. This
      chapter reviews the major methods available to researchers to adjust for the
      biases introduced by relatedness and maximize power to detect associations. The
      advantages and disadvantages of different methods are presented with reference to
      elements of study design, population characteristics, and computational
      requirements.

PMID- 27896743
TI  - Analysis of Quantitative Trait Loci.
AB  - Although the term quantitative trait locus (QTL) strictly refers merely to a
      genetic variant that causes changes in a quantitative phenotype such as height,
      QTL analysis more usually describes techniques used to study oligogenic or
      polygenic traits where each identified locus contributes a relatively small
      amount to the genetic determination of the trait, which may be categorical in
      nature. Originally, too, it would be clear that it covered segregation and
      genetic linkage analysis, but now genetic association analysis in a genome-wide
      SNP or sequencing experiment would be the commonest application. The same
      biometrical genetic statistical apparatus used in this setting-analysis of
      variance, linear or generalized linear mixed models-can actually be applied to
      categorical phenotypes, as well as to multiple traits simultaneously, dealing
      with and taking advantage of genetic pleiotropy. Most recently, they are being
      used to make inferences about population and evolutionary genetics, with
      applications ranging from human disease to control of disease-causing organisms.
      Several computer software packages make it relatively straightforward to fit
      these statistically complex models to the large amounts of genotype and phenotype
      data routinely collected today.

PMID- 27896744
TI  - High-Dimensional Profiling for Computational Diagnosis.
AB  - New technologies allow for high-dimensional profiling of patients. For instance,
      genome-wide gene expression analysis in tumors or in blood is feasible with
      microarrays, if all transcripts are known, or even without this restriction using
      high-throughput RNA sequencing. Other technologies like NMR finger printing allow
      for high-dimensional profiling of metabolites in blood or urine. Such
      technologies for high-dimensional patient profiling represent novel possibilities
      for molecular diagnostics. In clinical profiling studies, researchers aim to
      predict disease type, survival, or treatment response for new patients using high
      dimensional profiles. In this process, they encounter a series of obstacles and
      pitfalls. We review fundamental issues from machine learning and recommend a
      procedure for the computational aspects of a clinical profiling study.

PMID- 27896745
TI  - Molecular Similarity Concepts for Informatics Applications.
AB  - The assessment of small molecule similarity is a central task in chemoinformatics
      and medicinal chemistry. A variety of molecular representations and metrics are
      applied to computationally evaluate and quantify molecular similarity. A
      critically important aspect of molecular similarity analysis in chemoinformatics
      and pharmaceutical research is that one is typically not interested in
      quantifying the degree of structural or chemical similarity between compounds per
      se, but rather in extrapolating from molecular similarity to property similarity.
      In other words, one assumes that there is a correlation between calculated
      similarity and specific properties of small molecules including, first and
      foremost, biological activities. Although similarity is a priori a subjective
      concept, and difficult to quantify, it must computationally be assessed in a
      formally consistent manner. Otherwise, there is little utility of similarity
      calculations. Consistent treatment requires approximations to be made and the
      consideration of alternative computational similarity concepts, as discussed
      herein.

PMID- 27896746
TI  - Compound Data Mining for Drug Discovery.
AB  - In recent years, there has been unprecedented growth in compound activity data in
      the public domain. These compound data provide an indispensable resource for drug
      discovery in academic environments as well as in the pharmaceutical industry. To
      handle large volumes of heterogeneous and complex compound data and extract
      discovery-relevant knowledge from these data, advanced computational mining
      approaches are required. Herein, major public compound data repositories are
      introduced, data confidence criteria reviewed, and selected data mining
      approaches discussed.

PMID- 27896747
TI  - Studying Antibody Repertoires with Next-Generation Sequencing.
AB  - Next-generation sequencing is making it possible to study the antibody repertoire
      of an organism in unprecedented detail, and, by so doing, to characterize its
      behavior in the response to infection and in pathological conditions such as
      autoimmunity and cancer. The polymorphic nature of the repertoire poses unique
      challenges that rule out the use of many commonly used NGS methods and require
      tradeoffs to be made when considering experimental design.We outline the main
      contexts in which antibody repertoire analysis has been used, and summarize the
      key tools that are available. The humoral immune response to vaccination has been
      a particular focus of repertoire analyses, and we review the key conclusions and
      methods used in these studies.

PMID- 27896748
TI  - Using the QAPgrid Visualization Approach for Biomarker Identification of Cell
      Specific Transcriptomic Signatures.
AB  - In this chapter, we illustrate the use of an integrated mathematical method for
      joint clustering and visualization of large-scale datasets. In applying these
      clustering methodologies to biological datasets, we aim to identify
      differentially expressed genes according to cell type by building molecular
      signatures supported by statistical scores. In doing so, we also aim to find a
      global map of highly co-expressed clusters. Variations in these clusters may well
      indicate other pathological trends and changes.

PMID- 27896749
TI  - Computer-Aided Breast Cancer Diagnosis with Optimal Feature Sets: Reduction Rules
      and Optimization Techniques.
AB  - This chapter introduces a new method for knowledge extraction from databases for
      the purpose of finding a discriminative set of features that is also a robust set
      for within-class classification. Our method is generic and we introduce it here
      in the field of breast cancer diagnosis from digital mammography data. The
      mathematical formalism is based on a generalization of the k-Feature Set problem
      called (alpha, beta)-k-Feature Set problem, introduced by Cotta and Moscato (J
      Comput Syst Sci 67(4):686-690, 2003). This method proceeds in two steps: first,
      an optimal (alpha, beta)-k-feature set of minimum cardinality is identified and
      then, a set of classification rules using these features is obtained. We obtain
      the (alpha, beta)-k-feature set in two phases; first a series of extremely
      powerful reduction techniques, which do not lose the optimal solution, are
      employed; and second, a metaheuristic search to identify the remaining features
      to be considered or disregarded. Two algorithms were tested with a public domain
      digital mammography dataset composed of 71 malignant and 75 benign cases. Based
      on the results provided by the algorithms, we obtain classification rules that
      employ only a subset of these features.

PMID- 27896750
TI  - Inference Method for Developing Mathematical Models of Cell Signaling Pathways
      Using Proteomic Datasets.
AB  - The progress in proteomics technologies has led to a rapid accumulation of large
      scale proteomic datasets in recent years, which provides an unprecedented
      opportunity and valuable resources to understand how living organisms perform
      necessary functions at systems levels. This work presents a computational method
      for designing mathematical models based on proteomic datasets. Using the mitogen
      activated protein (MAP) kinase pathway as the test system, we first develop a
      mathematical model including the cytosolic and nuclear subsystems. A key step of
      modeling is to apply a genetic algorithm to infer unknown model parameters. Then
      the robustness property of mathematical models is used as a criterion to select
      appropriate rate constants from the estimated candidates. Moreover, quantitative
      information such as the absolute protein concentrations is used to further refine
      the mathematical model. The successful application of this inference method to
      the MAP kinase pathway suggests that it is a useful and powerful approach for
      developing accurate mathematical models to gain important insights into the
      regulatory mechanisms of cell signaling pathways.

PMID- 27896751
TI  - Clustering.
AB  - Clustering techniques are used to arrange genes in some natural way, that is, to
      organize genes into groups or clusters with similar behavior across relevant
      tissue samples (or cell lines). These techniques can also be applied to tissues
      rather than genes. Methods such as hierarchical agglomerative clustering, k-means
      clustering, the self-organizing map, and model-based methods have been used. Here
      we focus on mixtures of normals to provide a model-based clustering of tissue
      samples (gene signatures) and of gene profiles, including time-course gene
      expression data.

PMID- 27896752
TI  - Parameterized Algorithmics for Finding Exact Solutions of NP-Hard Biological
      Problems.
AB  - Fixed-parameter algorithms are designed to efficiently find optimal solutions to
      some computationally hard (NP-hard) problems by identifying and exploiting
      "small" problem-specific parameters. We survey practical techniques to develop
      such algorithms. Each technique is introduced and supported by case studies of
      applications to biological problems, with additional pointers to experimental
      results.

PMID- 27896753
TI  - Information Visualization for Biological Data.
AB  - Visualization is a powerful method to present and explore a large amount of data.
      It is increasingly important in the life sciences and is used for analyzing
      different types of biological data, such as structural information, high
      throughput data, and biochemical networks. This chapter gives a brief
      introduction to visualization methods for bioinformatics, presents two commonly
      used techniques in detail, and discusses a graphical standard for biological
      networks and cellular processes.

PMID- 27896754
TI  - Application of Multiplex Biomarker Approaches to Accelerate Drug Discovery and
      Development.
AB  - Multiplex biomarker tests are becoming an essential part of the drug development
      process. This chapter explores the role of biomarker-based tests as effective
      tools in improving preclinical research and clinical development, and the
      challenges that this presents. The potential of incorporating biomarkers in the
      clinical pipeline to improve decision making, accelerate drug development,
      improve translation, and reduce development costs is discussed. This chapter also
      discusses the latest biomarker technologies in use to make this possible and
      details the next steps that must undertaken to keep driving this process
      forwards.

PMID- 27896755
TI  - The Application of Multiplex Biomarker Techniques for Improved Stratification and
      Treatment of Schizophrenia Patients.
AB  - In the case of major psychiatric disorders such as schizophrenia, shortcomings in
      the conversion of scientific discoveries into newer and safer treatment options
      has led to a loss of confidence and precipitated a crisis for large
      pharmaceutical companies. This chapter describes how incorporation of multiplex
      biomarker approaches into the clinical pipeline can lead to better patient
      characterization, delivery of novel treatment approaches and help to renew
      efforts in this important area. The development of specific biomarker test panels
      for disease prediction should facilitate early intervention strategies, which may
      help to slow disease development or progression. Furthermore, the development of
      such tests using lab-on-a-chip and smartphone platforms will help to shift
      diagnosis and treatment of this major disorder into a point-of-care setting for
      improved patient outcomes.

PMID- 27896756
TI  - Multiplex Biomarker Approaches in Type 2 Diabetes Mellitus Research.
AB  - Type 2 diabetes mellitus is a multifactorial condition resulting in high fasting
      blood glucose levels. Although its diagnosis is straightforward, there is not one
      set of biomarkers or drug targets that can be used for classification or
      personalized treatment of individuals who suffer from this condition. Instead,
      the application of multiplex methods incorporating a systems biology approach is
      essential in order to increase our understanding of this disease. This chapter
      reviews the state of the art in biomarker studies of human type 2 diabetes from a
      proteomic and metabolomic perspective. Our main focus was on biomarkers for
      disease prediction as these could lead to early intervention strategies for the
      best possible patient outcomes.

PMID- 27896757
TI  - LC-MSE, Multiplex MS/MS, Ion Mobility, and Label-Free Quantitation in Clinical
      Proteomics.
AB  - Proteomic tools can only be implemented in clinical settings if high-throughput,
      automated, sensitive, and accurate methods are developed. This has driven
      researchers to the edge of mass spectrometry (MS)-based proteomics capacity. Here
      we provide an overview of recent achievements in mass spectrometric technologies
      and instruments. This includes development of high and ultra definition-MSE
      (HDMSE and UDMSE) through implementation of ion mobility (IM) MS towards
      sensitive and accurate label-free proteomics using ultra performance liquid
      chromatography (UPLC). Label free UPLC-HDMSE is less expensive than labeled-based
      quantitative proteomics and has no limits regarding the number of samples that
      can be analyzed and compared, which is an important requirement for supporting
      clinical applications.

PMID- 27896758
TI  - Phenotyping Multiple Subsets of Immune Cells In Situ in FFPE Tissue Sections: An
      Overview of Methodologies.
AB  - The recent clinical success of new cancer immunotherapy agents and methods is
      driving the need to understand the role of immune cells in solid tissues,
      especially tumors. Immune cell phenotyping via flow cytometry, while a
      cornerstone of immunology, is not spatially resolved and cannot analyze immune
      cell subsets in situ in clinical biopsy sections or to determine their
      interrelationships. To address this problem, a number of methodologies have been
      developed in attempts to phenotype immune and other cells in images acquired from
      tissue sections and to assess their organization in the tumor and its
      microenvironment. This chapter review the staining and multiplex image analysis
      methods that have been developed for phenotyping immune and other cells in
      formalin-fixed, paraffin-embedded (FFPE) tissue sections.

PMID- 27896759
TI  - Identification and Clinical Translation of Biomarker Signatures: Statistical
      Considerations.
AB  - Powerful machine learning tools exist to extract biological patterns for
      diagnosis or prediction from high-dimensional datasets. Simultaneous advances in
      high-throughput profiling technologies have led to a rapid acceleration of
      biomarker discovery investigations across all areas of medicine. However, the
      translation of biomarker signatures into clinically useful tools has thus far
      been difficult. In this chapter, several important considerations are discussed
      that influence such translation in the context of classifier design. These
      include aspects of variable selection that go beyond classification accuracy, as
      well as effects of variability on assay stability and sample size. The
      consideration of such factors may lead to an adaptation of biomarker discovery
      approaches, aimed at an optimal balance of performance and clinical
      translatability.

PMID- 27896760
TI  - Opportunities and Challenges of Multiplex Assays: A Machine Learning Perspective.
AB  - Multiplex assays that allow the simultaneous measurement of multiple analytes in
      small sample quantities have developed into a widely used technology. Their
      implementation spans across multiple assay systems and can provide readouts of
      similar quality as the respective single-plex measures, albeit at far higher
      throughput. Multiplex assay systems are therefore an important element for
      biomarker discovery and development strategies but analysis of the derived data
      can face substantial challenges that may limit the possibility of identifying
      meaningful biological markers. This chapter gives an overview of opportunities
      and challenges of multiplexed biomarker analysis, in particular from the
      perspective of machine learning aimed at identification of predictive biological
      signatures.

PMID- 27896761
TI  - Multiplex Analyses Using Real-Time Quantitative PCR.
AB  - Quantitative polymerase chain reaction (qPCR) is a routinely used method for the
      detection and quantitation of gene expression in real time. Multiplex qPCR
      requires the use of probe-based assays, in which each probe is labeled with a
      unique fluorescent dye, resulting in different observed colors for each assay.
      The signal from each dye is used to quantitate the amount of each target
      separately in the same tube or well. The availability to multiplex therefore
      allows the measurement of the expression levels of several targets or genes of
      interest quickly. Here, we describe a method using the SensiFAST and SensiFAST
      One-Step probe kits which allows simultaneous real-time quantitation of up to 5
      amplicons.

PMID- 27896762
TI  - Multiplex Analysis Using cDNA Transcriptomic Profiling.
AB  - DNA microarrays contain microscopic DNA spots attached to a solid surface. Each
      spot contains picomolar levels of a specific DNA probe sequence and hybridization
      to the corresponding gene products can be detected and quantitated through the
      use of fluorescently labeled target DNA. In this format, DNA microarrays can be
      used to measure the expression level of thousands of genes in a single
      experiment. Here, we present a method to detect the mRNA transcriptional changes
      in neuronal precursor cells following differentiation using high density cDNA
      microarrays.

PMID- 27896763
TI  - Multiplex Single Nucleotide Polymorphism Analyses.
AB  - Quantitative polymerase chain reaction (qPCR) is a routinely used method for
      detection and quantitation of gene expression in real time. This is achieved
      through the incorporation and measurement of fluorescent reporter probes in the
      amplified cDNA strands, since the fluorescent signals increase as the reaction
      progresses. The availability of multiple probes that fluoresce at different
      wavelengths allows for multiplexing as this gives rise to amplicons with unique
      fluorescent signatures. Here, we describe a method using the SensiFAST and
      SensiFAST One-Step probe kits which allows simultaneous real-time quantitation of
      up to 5 amplicons.

PMID- 27896764
TI  - Pulsed SILAC as a Approach for miRNA Targets Identification in Cell Culture.
AB  - Pulsed stable isotope labeling by amino acids in cell culture (pSILAC) comprises
      a variation of the classical SILAC proteomic methodology that enables the
      identification of short-term proteomic responses such as those elicited by micro
      RNAs (miRNAs). Here, we describe a detailed pSILAC protocol for global
      identification and quantification of protein translation alterations induced by a
      miRNA using 3T3-L1 pre-adipocytes as a model system.

PMID- 27896765
TI  - Blood Bio-Sampling Procedures for Multiplex Biomarkers Studies.
AB  - A major challenge in single or panel of biomarker discovery and validation is the
      inherent biological complexity underlying disease heterogeneity and inconsistent
      responses to treatment. Moreover, the lack of standardization in the sampling,
      processing, and storage of biological fluids such as plasma and serum disrupts
      the discovery and validation of blood-based biomarker tests in preclinical and
      clinical settings. This chapter presents a reproducible sample collection and
      handling procedure that aims to enhance analyte stability and ensure
      compatibility with the corresponding multiplex biomarker profiling platforms. The
      importance of defining bio-sample acquisition and processing, study design, and
      profiling platform guidelines for blood-based biomarker measurements is paramount
      for the success of personalized healthcare strategy and development of companion
      diagnostics.

PMID- 27896766
TI  - Multiplex Immunoassay Profiling.
AB  - Multiplex immunoassays allow for the rapid profiling of biomarker proteins in
      biological fluids, using less sample and labor than single immunoassays. This
      chapter details the methods to develop and manufacture multiplex assays for the
      Luminex(r) platform. Although assay development is not included here, the same
      methods can be used to covalently couple antibodies to the Luminex beads and to
      label antibodies for the screening of sandwich pairs, if needed. The assay
      optimization, detection of cross-reactivity, and minimizing antibody interactions
      and matrix interferences will be addressed.

PMID- 27896767
TI  - Multiplex Sequential Immunoprecipitation of Insulin Secretory Granule Proteins
      from Radiolabeled Pancreatic Islets.
AB  - Pulse radiolabeling of cells with radioactive amino acids is a common method for
      tracking the biosynthesis of proteins. Specific proteins can then be
      immunoprecipitated and analyzed by electrophoresis and imaging techniques. This
      chapter presents a protocol for the biosynthetic labeling of pancreatic islets
      with 35S-methionine, followed by multiplex sequential immunoprecipitation of
      insulin and three other secretory granule accessory proteins. This provided a
      means of distinguishing those pancreatic islet proteins with different
      biosynthetic rates in response to the media glucose concentrations.

PMID- 27896768
TI  - Two Dimensional Gel Electrophoresis of Insulin Secretory Granule Proteins from
      Biosynthetically-Labeled Pancreatic Islets.
AB  - Pulse-chase radiolabeling of cells with radioactive amino acids is a common
      method for tracking the biosynthesis of proteins. Radiolabeled newly synthesized
      proteins can be analyzed by a number of techniques such as two dimensional gel
      electrophoresis (2DE). This chapter presents a protocol for the biosynthetic
      labeling of pancreatic islets with 35S-methionine in the presence of basal and
      stimulatory concentrations of glucose, followed by subcellular fractionation to
      produce a secretory granule fraction and analysis of the granule protein contents
      by 2DE. This provides a means of determining whether or not the biosynthetic
      rates of the entire granule constituents are coordinately regulated.

PMID- 27896769
TI  - Depletion of Highly Abundant Proteins of the Human Blood Plasma: Applications in
      Proteomics Studies of Psychiatric Disorders.
AB  - Psychiatric disorders are complex diseases involving exogenous and endogenous
      factors. Biomarkers for diagnosis or prediction of successful treatment are not
      existent. In addition, the molecular basis of these diseases is still poorly
      understood. Blood plasma represents the most complex proteome as it contains
      subproteomes from several body tissues. However, the high abundance of some
      little proteins can obscure the analysis of hundreds of low abundance proteins,
      which are potential biomarkers. Therefore, removal of these high abundance
      proteins is pivotal in any proteomic study of plasma. Here, we present a method
      of depleting these proteins using immunoaffinity liquid chromatography.

PMID- 27896770
TI  - Simultaneous Two-Dimensional Difference Gel Electrophoresis (2D-DIGE) Analysis of
      Two Distinct Proteomes.
AB  - This chapter describes the basics, applications, and limitations of two
      dimensional gel electrophoresis (2DE) and two-dimensional difference gel
      electrophoresis (2D-DIGE) for multiplex analysis of distinct proteomes. We also
      propose a basic protocol for 2D-DIGE, technique that allows the analysis of
      paired protein extracts, which are labeled with fluorescent Cy3 and Cy5 dyes and
      electrophoresed with a Cy2-labeled standard extract on the same 2DE gels.
      Scanning the gels at wavelengths specific for each dye allows direct overlay the
      two different proteomes and the differences in abundance of specific protein
      spots can be determined.

PMID- 27896771
TI  - Selective Reaction Monitoring for Quantitation of Cellular Proteins.
AB  - Proteins and proteomes are dynamic and complex. The accurate identification and
      measurement of their properties such as abundance, location, and turnover are
      challenging tasks. Even though high-throughput proteomics has significantly
      evolved, the technique still lacks fully quantitative and reproducible qualities.
      A mass spectrometry-based targeted proteomic strategy called selective reaction
      monitoring (SRM) has emerged in recent years as an important multiplex platform
      to precisely quantify sets of proteins in multiple samples. This has several
      advantages in terms of sensitivity, reproducibility, and sample consumption
      compared to classical methods including those based on antibodies. Here, we
      present a detailed protocol for quantitation of panels of proteins from cell line
      extracts using the SRM targeted proteomics approach.

PMID- 27896772
TI  - Characterization of a Protein Interactome by Co-Immunoprecipitation and Shotgun
      Mass Spectrometry.
AB  - Identifying the partners of a given protein (the interactome) may provide leads
      about the protein's function and the molecular mechanisms in which it is
      involved. One of the alternative strategies used to characterize protein
      interactomes consists of co-immunoprecipitation (co-IP) followed by shotgun mass
      spectrometry. This enables the isolation and identification of a protein target
      in its native state and its interactome from cells or tissue lysates under
      physiological conditions. In this chapter, we describe a co-IP protocol for
      interactome studies that uses an antibody against a protein of interest bound to
      protein A/G plus agarose beads to isolate a protein complex. The interacting
      proteins may be further fractionated by SDS-PAGE, followed by in-gel tryptic
      digestion and nano liquid chromatography high-resolution tandem mass spectrometry
      (nLC ESI-MS/MS) for identification purposes. The computational tools, strategy
      for protein identification, and use of interactome databases also will be
      described.

PMID- 27896773
TI  - Using 15N-Metabolic Labeling for Quantitative Proteomic Analyses.
AB  - Quantitative proteomics has benefited from the application of stable isotope
      labeling-based approaches. Using stable isotopically labeled material as an
      internal standard in proteomic comparisons allows an unbiased and accurate
      quantification of protein expression level changes. Here, we describe the use of
      in vivo 15N metabolic labeling to generate labeled protein standards from mice.
      We then present a protocol including sample preparation, mass spectrometry, and
      data analysis workflows using these standards to compare unlabeled proteomes. We
      focus on mouse brain tissue and plasma samples, although this conceptual
      framework can be applied to most organisms.

PMID- 27896774
TI  - Multiplex Measurement of Serum Folate Vitamers by UPLC-MS/MS.
AB  - The implementation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method to measure six folate vitamers in serum samples allows a more individual
      and accurate measurement than the commonly used immunoassays. In the described
      method, serum samples undergo solid phase extraction followed by liquid
      chromatography coupled with electrospray ionization tandem mass spectrometry with
      a run time of 3.5 min. Recovery is 95 % for the most important folate metabolite,
      5-methyltetrahydrofolate (MTHF), and greater than 78 % for other minor folate
      forms. The limit of detection ranges from 0.2 to 0.4 nmol/L with a intra-batch
      imprecision of less than 7 % for all analytes and calibration ranges of 1-100
      nmol/L for MTHF and 0.5-20 nmol/L for the minor folate forms, with greater than
      0.99 R2 linearity.

PMID- 27896775
TI  - UPLC-MS/MS Determination of Deuterated 25-Hydroxyvitamin D (d3-25OHD3) and Other
      Vitamin D Metabolites for the Measurement of 25OHD Half-Life.
AB  - Plasma 25-hydroxyvitamin D (25OHD) half-life (25OHDt 1/2) is a dynamic marker of
      vitamin D metabolism that can be used to assess vitamin D expenditure and help
      inform vitamin D requirements. Our group recently established an approach to
      determine the 25OHDt 1/2 as an alternative biomarker of 25OHD expenditure in
      humans. The approach uses a small oral dose of stable isotope labeled 25OHD3 [3
      2H-25OHD3 (6,19,19-d3)] (d3-25OHD3) (tracer), which is distinguishable from
      endogenous 25OHD by liquid chromatography tandem-mass spectrometry (LC-MS/MS). We
      report here the method, which relies on protein precipitation, purification with
      solid phase extraction, derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione
      (PTAD), and determination of the compounds by isotope-dilution UPLC-MS/MS. The
      method proved to be rapid and sensitive (LOQ 0.2 nmol/L) for the quantification
      of this tracer as well as the other vitamin D metabolites: 25OHD3, 25OHD2, and
      24,25(OH)2D3 in human plasma.

PMID- 27896776
TI  - iTRAQ-Based Shotgun Proteomics Approach for Relative Protein Quantification.
AB  - Shotgun proteomics has a key role in quantitative estimation of proteins from
      biological systems under different conditions, which is crucial in the
      understanding of their functional roles. Isobaric tagging for relative and
      absolute quantitation (iTRAQ) mass spectrometry is based on pre-labeling of
      peptides with mass tags which allows the multiplex analysis of up to eight
      proteomes simultaneously. We describe here a detailed protocol for sample
      preparation and iTRAQ 4-plex labeling for relative quantification of multiple
      samples from human and plant tissues. We also present two strategies for peptide
      fractionation after the iTRAQ labeling protocol.

PMID- 27896778
TI  - Lab-on-a-Chip Multiplex Assays.
AB  - Lab-on-a-chip multiplex assays allow a rapid identification of multiple
      parameters in an automated manner. Here we describe a lab-based preparation
      followed by a rapid and fully automated DNA microarray hybridization and readout
      in less than 10 min using the Fraunhofer in vitro diagnostics (ivD) platform to
      enable rapid identification of bacterial species and detection of antibiotic
      resistance. The use of DNA microarrays allows a fast adaptation of new biomarkers
      enabling the identification of different genes as well as single-nucleotide
      polymorphisms (SNPs) within these genes. In this protocol we describe a DNA
      microarray developed for identification of Staphylococcus aureus and the mecA
      resistance gene.

PMID- 27896777
TI  - 1H NMR Metabolomic Profiling of Human and Animal Blood Serum Samples.
AB  - Nuclear magnetic resonance (NMR) spectroscopy techniques allow the acquisition of
      a large amount of data and when combined with multivariate statistical analysis,
      it is possible to process and interpret the obtained NMR data in accordance with
      the biological problem being investigated. In this chapter, the search for
      biologically relevant biomarkers is addressed using NMR spectroscopy-based
      metabolomics, due to their clinical relevance for either diagnosis or monitoring
      of diseases and disorders.

PMID- 27896779
TI  - Multiplex Smartphone Diagnostics.
AB  - Increasing computing power in smartphones allows for their transformation into
      point-of-care diagnostic devices. Mobile medical diagnostic applications enable
      utilization of the processing capabilities of smartphones through their cameras.
      Hardware attachments or stand-alone versions of smartphone diagnostics have the
      capability to revolutionize quantitative readouts. Here, we describe a protocol
      for quantifying commercial colorimetric diagnostic tests with a stand-alone
      smartphone application. This approach can be used in the multiplexed analyses of
      biomarker readouts.

PMID- 27896780
TI  - Development of a User-Friendly App for Assisting Anticoagulation Treatment.
AB  - Blood coagulation time is an important factor to consider for postoperative and
      cardiac disorder patients who have been prescribed anticoagulant coagulant
      medications. This chapter describes a patient self-management system for
      assessment of blood coagulation times and determining appropriate anticoagulant
      dosages using a test strip device and the Coagu app. This app can also be used as
      a patient reminder of treatment times and to monitor treatment and effects over
      time.

PMID- 27896781
TI  - Multiplex Biomarker Approaches to Enable Point-of-Care Testing and Personalized
      Medicine.
AB  - This chapter describes how current and future innovations driven by application
      of multiplex biomarker techniques can help in earlier and more efficacious
      treatment of patients, suffering from the world's most devastating and costly
      diseases. The application of new miniaturized biosensors and transducers will
      enable point-of-care testing by facilitating analysis of a single drop of a blood
      within the time span of a visit to the doctor's office. It is anticipated that
      the scoring algorithms used with future tests will incorporate both biochemical
      and clinical data, resulting in specific profiles for each patient or tested
      subject to enable personalized medicine approaches.

PMID- 27896782
TI  - Mixed method versus full top-down microcosting for organ recovery cost assessment
      in a French hospital group.
AB  - BACKGROUND: The costing method used can change the results of economic
      evaluations. Choosing the appropriate method to assess the cost of organ recovery
      is an issue of considerable interest to health economists, hospitals, financial
      managers and policy makers in most developed countries. OBJECTIVES: The main
      objective of this study was to compare a mixed method, combining top-down
      microcosting and bottom-up microcosting versus full top-down microcosting to
      assess the cost of organ recovery in a French hospital group. The secondary
      objective was to describe the cost of kidney, liver and pancreas recovery from
      French databases using the mixed method. METHODS: The resources consumed for each
      donor were identified and valued using the proposed mixed method and compared to
      the full top-down microcosting approach. Data on kidney, liver and pancreas
      recovery were collected from a medico-administrative French database for the
      years 2010 and 2011. Related cost data were recovered from the hospital cost
      accounting system database for 2010 and 2011. Statistical significance was
      evaluated at P < 0.05. RESULTS: All the median costs for organ recovery differ
      significantly between the two costing methods (non-parametric test method; P <
      0.01). Using the mixed method, the median cost for recovering kidneys was found
      to be ?5155, liver recovery was ?2528 and pancreas recovery was ?1911. Using the
      full top-down microcosting method, median costs were found to be 21-36% lower
      than with the mixed method. CONCLUSION: The mixed method proposed appears to be a
      trade-off between feasibility and accuracy for the identification and valuation
      of cost components when calculating the cost of organ recovery in comparison to
      the full top-down microcosting approach.

PMID- 27896783
TI  - Post-clear corneal phacoemulsification endophthalmitis: profile and management
      outcomes at a tertiary eye care center in western India.
AB  - BACKGROUND: Infectious endophthalmitis is a serious sight threatening intraocular
      inflammation that results from exogenous or endogenous spread of organisms into
      the eye.A retrospective case series to study the profile of endophthalmitis
      following clear corneal phacoemulsification in western India between years 2008
      and 2014 was held in the National Institute of Ophthalmology, Pune, India. Cases
      of endophthalmitis post-clear corneal phacoemulsification were reviewed
      pertaining to demography, clinical history, surgeon experience, surgical
      complications, time of onset following surgery, duration between onset of
      symptoms and presentation to the center, presenting visual acuity and at follow
      ups, slit-lamp examination and ultrasound findings, vitreous tap culture results,
      treatment, and final functional and anatomical outcomes. RESULTS: Of 60 cases, 34
      were operated in the tertiary center and 26 were referred. The incidence of
      endophthalmitis post clear corneal phacoemulsification performed at the tertiary
      center was 0.17%. Mean time delay between onset of symptoms and presentation to
      the tertiary care center was 2.6 days. Fifty percent cases were culture +ve, of
      which 80% were Gram +ve and 20% were Gram -ve, no fungal isolates. Coagulase -ve
      staphylococcus was the most common causative organism; rare isolates included
      Sphingomonas paucimobilis and Streptococcus mitis. Twenty-six eyes underwent
      primary vitrectomy. Mean presenting visual acuity was 2.14 +/- 0.07 logMAR units
      which improved to logMAR 0.98 +/- 0.12 at final follow-up. Presenting VA was
      >20/200 in 13.3% and <HM in 60% cases. 66.7% of eyes had visual improvement;
      26.7% cases achieved VA 20/40 at final follow-up. Gram +ve and culture -ve cases,
      better presenting VA, and less time delay between onset and presentation had a
      favorable visual outcome. CONCLUSIONS: The shift of the clinico-microbiological
      spectrum of endophthalmitis could be due to change in surgical technique to clear
      corneal phacoemulsification. Predictors of good visual outcome include good
      presenting visual acuity, early presentation to the center, culture negativity,
      and coagulase negative organisms.

PMID- 27896784
TI  - Ocular involvement associated with varicella in adults.
AB  - BACKGROUND: Varicella is a common infectious disease primarily of childhood that
      is usually benign and self-limited. It is, however, increasingly seen in adults
      who are at a higher risk of severe infection. Ocular complications of varicella
      are relatively uncommon and have been rarely described in adults. We describe
      herein five adults who developed ocular involvement in association with primary
      varicella-zoster virus infection. FINDINGS: Ocular manifestations included acute
      anterior uveitis in four eyes, with associated stromal keratitis in one of them,
      epithelial ulcerative keratitis in the two eyes of one patient, and acute retinal
      necrosis in one eye. One patient with acute anterior uveitis was treated with
      topical steroids and cycloplegic agents. The four other patients received topical
      or systemic antiviral drugs, with subsequent resolution of acute ocular
      inflammatory disease. CONCLUSIONS: The spectrum of chickenpox-associated ocular
      complications in adults is wide. Early diagnosis and appropriate management are
      mandatory to improve visual outcome.

PMID- 27896785
TI  - Prescription Patterns of Medications for Alzheimer's Disease in Japan from 2010
      to 2015: A Descriptive Pharmacy Claims Database Study.
AB  - INTRODUCTION: Although four kinds of Alzheimer's disease (AD) drugs are available
      at present there was only one drug until 2011 in Japan. This study aimed to
      elucidate prescription trends of these medications for AD in Japanese outpatients
      before and after the new drug releases in 2011. METHODS: This descriptive study
      of pharmacy claims databases analyzed outpatient prescription data from community
      pharmacies across Japan. The study patients were 20 years or older and first
      administered medications for AD (donepezil, memantine, rivastigmine, or
      galantamine) between January 2010 and September 2014. They were grouped on the
      basis of the year of their initial medications for AD administration into the
      2010-2011 and 2012-2014 groups (1 and 2, respectively) and their characteristics
      and AD treatments were summarized by group. The subanalyses used a multivariable
      logistic regression model to examine the relationship between patient
      characteristics and discontinuation or change to combination therapy within a
      year. RESULTS: A total of 103,592 patients (group 1 and 2, 28,581 and 75,011,
      respectively) were prescribed medications for AD during the study period. The
      group 1 and 2 mean +/- standard deviation (SD) ages were 79.6 +/- 7.4 and 80.9 +/
      7.3 years while female patients constituted 64.0% and 64.5%, respectively.
      Furthermore, in groups 1 and 2 patients, 99.0% and 94.3% received a medication
      for AD monotherapy, 92.3% and 59.6% were prescribed donepezil, and 40.5% and
      41.5% discontinued treatment within a year, respectively. The subanalyses suggest
      that being at least 85 years old strongly correlated with treatment
      discontinuation and change to combination therapy within a year. CONCLUSION:
      Although the prescription proportions of the various medications for AD have
      changed since 2011, no apparent changes occurred in the patient characteristics
      of those who initiated AD treatment between 2010-2011 and 2012-2014.

PMID- 27896786
TI  - Construction of efficient Streptococcus zooepidemicus strains for hyaluoronic
      acid production based on identification of key genes involved in sucrose
      metabolism.
AB  - Biosynthesis of polysaccharide hyaluoronic acid (HA) by Streptococcus
      zooepidemicus is a carbon-intensive process. The carbon flux and factor(s)
      restricting HA yield were not well understood. Here, we investigated the function
      of genes involved in sucrose metabolism and identified targets limiting HA yield,
      which were exploited to construct efficient S. zooepidemicus strains for HA
      production. The sucrose uptake was addressed by deletion of scrA and scrB, which
      encodes sucrose-PTS permease and sucrose-6-phosphate hydrolase, respectively. We
      found that scrB was essential for the growth of S. zooepidemicus and HA
      biosynthesis, and accumulation of sucrose-6-phosphate was toxic. DeltascrB could
      not grow in THY-sucrose medium, while DeltascrA and DeltascrADeltascrB showed
      negligible growth defects. Overexpression of scrA significantly reduced biomass
      and HA production, while overexpression of scrB resulted in 26% increase of
      biomass and 30% increase of HA yield. We revealed that fructose-6-phosphate for
      HA biosynthesis mainly originates from glucose-6-phosphate. Deletion of scrK, a
      gene encoding hexokinase, led to 11% reduction of biomass and 12% decrease of HA
      yield, while deletion of hasE, a gene encoding phosphoglucoisomerase, resulted in
      the abolishment of HA biosynthesis and a significantly slow growth. We found that
      HA biosynthesis could be improved by directing carbon flux to fructose-6
      phosphate. Deletion of fruA encoding the EII of fructose-PTS and fruK encoding
      phosphofructokinase showed no apparent effect on cell growth, but resulted in 22
      and 27% increase of HA yield, respectively. Finally, a strain with 55% increase
      of HA was constructed by overexpression of scrB in DeltafruK. These results
      provide a solid foundation for further metabolic engineering of S. zooepidemicus
      for highly efficient HA production.

PMID- 27896788
TI  - Facile Synthesis and High Photocatalytic Degradation Performance of ZnO-SnO2
      Hollow Spheres.
AB  - ZnO-SnO2 hollow spheres were successfully synthesized through a hydrothermal
      method-combined carbon sphere template. The samples were characterized by X-ray
      diffraction (XRD), scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). The
      average diameter of hollow spheres is about 150 nm. The photocatalytic activity
      of the as-prepared samples was investigated by photodegrading Rhodamine B. The
      results indicated that the photocatalytic activities of ZnO-SnO2 hollow spheres
      are higher than ZnO hollow spheres. The degradation efficiency of the hollow
      spheres could reach 99.85% within 40 min, while the ZnO hollow spheres need 50
      min.

PMID- 27896787
TI  - Extracorporeal membrane oxygenation for pheochromocytoma-induced cardiogenic
      shock.
AB  - BACKGROUND: Pheochromocytoma, a rare catecholamine-producing tumor, might provoke
      stress-induced Takotsubo-like cardiomyopathy and severe cardiogenic shock.
      Because venoarterial-extracorporeal membrane oxygenation (VA-ECMO) rescue of
      pheochromocytoma-induced refractory cardiogenic shock has rarely been reported,
      we reviewed our ICU patients' presentations and outcomes. METHODS: All
      pheochromocytoma-induced refractory cardiogenic shock cases managed with VA-ECMO
      (January 2007-March 2015) were prospectively included and reviewed. We also
      performed a systematic review on this topic. RESULTS: Nine patients (7 women, 2
      men; 31-51 [median, 43 (IQR 36-49) years old]) were included; none had a
      previously known pheochromocytoma. Six of them had medical histories suggestive
      of the diagnosis: palpitations and headaches for several months for four,
      multiple endocrine neoplasia syndrome type 1 for one and recurrent Takotsubo
      disease for one; at hospital admission, all were hypertensive despite cardiogenic
      shock. Three others had an identified surgical triggering factor. All nine
      patients rapidly developed refractory cardiogenic shock with very severe left
      ventricular (LV) impairment (LV ejection-fraction range 5-20%; LV outflow-tract
      velocity-time integral range 3-8 cm). Seven patients' abdominal computed
      tomography scans showed pheochromocytoma-suggestive adrenal gland tumors (no scan
      during ICU stay for 2). Despite VA-ECMO implantation, three patients died of
      refractory multiple organ failure. For the six others, myocardial function
      improved and ECMO was removed 3-7 days post-implantation; alpha- and beta
      blockers were progressively introduced. Five survivors underwent pheochromocytoma
      excision 3 weeks-4 months post-ICU discharge, with satisfactory outcomes. One
      patient, whose pheochromocytoma was diagnosed 1 year after the index event,
      underwent uneventful surgical adrenalectomy. Systematic review retrieved 40 cases
      of pheochromocytoma-induced cardiogenic shock requiring mechanical support
      (mostly ECMO), with a mortality rate of 7%. Pheochromocytoma was removed
      surgically after mechanical support weaning in 31 patients and during mechanical
      support in 5. Four were not operated. CONCLUSIONS: Pheochromocytoma is a rare but
      reversible cause of cardiogenic shock amenable to VA-ECMO rescue. Adrenal gland
      imaging should be obtained for all patients with unexplained cardiogenic shock.
      Lastly, it might be safer to perform adrenalectomy several weeks after the
      initial catastrophic presentation, once recovery of LV systolic function is
      complete.

PMID- 27896789
TI  - MHD Natural Convection Flow of Casson Nanofluid over Nonlinearly Stretching Sheet
      Through Porous Medium with Chemical Reaction and Thermal Radiation.
AB  - In the present work, the effects of chemical reaction on hydromagnetic natural
      convection flow of Casson nanofluid induced due to nonlinearly stretching sheet
      immersed in a porous medium under the influence of thermal radiation and
      convective boundary condition are performed numerically. Moreover, the effects of
      velocity slip at stretching sheet wall are also examined in this study. The
      highly nonlinear-coupled governing equations are converted to nonlinear ordinary
      differential equations via similarity transformations. The transformed governing
      equations are then solved numerically using the Keller box method and graphical
      results for velocity, temperature, and nanoparticle concentration as well as wall
      shear stress, heat, and mass transfer rate are achieved through MATLAB software.
      Numerical results for the wall shear stress and heat transfer rate are presented
      in tabular form and compared with previously published work. Comparison reveals
      that the results are in good agreement. Findings of this work demonstrate that
      Casson fluids are better to control the temperature and nanoparticle
      concentration as compared to Newtonian fluid when the sheet is stretched in a
      nonlinear way. Also, the presence of suspended nanoparticles effectively promotes
      the heat transfer mechanism in the base fluid.

PMID- 27896790
TI  - Free Volume Structure of Acrylic-Type Dental Nanocomposites Tested with
      Annihilating Positrons.
AB  - Positron annihilation spectroscopy in lifetime measuring mode exploring
      conventional fast-fast coincidence ORTEC system is employed to characterize free
      volume structure of commercially available acrylic-type dental restorative
      composite Charisma(r) (Heraeus Kulzer GmbH, Germany). The measured lifetime
      spectra for uncured and light-cured composites are reconstructed from
      unconstrained x3-term fitting and semi-empirical model exploring x3-x2-coupling
      decomposition algorithm. The governing channel of positron annihilation in the
      composites studied is ascribed to mixed positron-Ps trapping, where Ps decaying
      in the third component is caused entirely by input from free-volume holes in
      polymer matrix, while the second component is defined by free positron trapping
      in interfacial free-volume holes between filler nanoparticles and surrounded
      polymer matrix. Microstructure scenario of the photopolymerization shrinkage
      includes cross-linking of structural chains in polymer matrix followed by
      conversion of bound positron-electron (positronium) traps in positron-trapping
      interfacial free-volume voids in a vicinity of agglomerated filler nanoparticles.

PMID- 27896792
TI  - Observation of Quantum Size Effect from Silicon Nanowall.
AB  - We developed a fabrication technique of very thin silicon nanowall structures.
      The minimum width of the fabricated silicon nanowall structures was about 3 nm.
      This thinnest region of the silicon nanowall structures was investigated by using
      cathode luminescence and ultraviolet photoelectron spectroscopy (UPS). The UPS
      measurements revealed that the density of states (DOS) of the thinnest region
      showed a stepwise shape which is completely different from that of the bulk Si.
      Theoretical analysis clearly demonstrated that this change of the DOS shape was
      due to the quantum size effect.

PMID- 27896791
TI  - The Application of Nano-TiO2 Photo Semiconductors in Agriculture.
AB  - Nanometer-sized titanium dioxide (TiO2) is an environmentally friendly optical
      semiconductor material. It has wide application value in many fields due to its
      excellent structural, optical, and chemical properties. The photocatalytic
      process of nano-TiO2 converts light energy into electrical or chemical energy
      under mild conditions. In recent years, the study and application of nano-TiO2 in
      the agricultural sector has gradually attracted attention. The nano-TiO2
      applications of degrading pesticides, plant germination and growth, crop disease
      control, water purification, pesticide residue detection, etc. are good
      prospects. This review describes all of these applications and the research
      status and development, including the underlying principles, features,
      comprehensive applications, functional modification, and potential future
      directions, for TiO2 in agriculture.

PMID- 27896793
TI  - Self-Assembled Formation of Well-Aligned Cu-Te Nano-Rods on Heavily Cu-Doped ZnTe
      Thin Films.
AB  - Cu doping of ZnTe, which is an important semiconductor for various optoelectronic
      applications, has been successfully achieved previously by several techniques.
      However, besides its electrical transport characteristics, other physical and
      chemical properties of heavily Cu-doped ZnTe have not been reported. We found an
      interesting self-assembled formation of crystalline well-aligned Cu-Te nano-rods
      near the surface of heavily Cu-doped ZnTe thin films grown via the molecular beam
      epitaxy technique. A phenomenological growth model is presented based on the
      observed crystallographic morphology and measured chemical composition of the
      nano-rods using various imaging and chemical analysis techniques. When
      substitutional doping reaches its limit, the extra Cu atoms favor an up-migration
      toward the surface, leading to a one-dimensional surface modulation and formation
      of Cu-Te nano-rods, which explain unusual observations on the reflection high
      energy electron diffraction patterns and apparent resistivity of these thin
      films. This study provides an insight into some unexpected chemical reactions
      involved in the heavily Cu-doped ZnTe thin films, which may be applied to other
      material systems that contain a dopant having strong reactivity with the host
      matrix.

PMID- 27896794
TI  - Efficacy and safety of ultrasound-guided placement of central venous port systems
      via the right internal jugular vein in elderly oncologic patients: our single
      center experience and protocol.
AB  - BACKGROUND: Ultrasound-guidance has become the routine method for internal
      jugular vein (IJV) catheterization reducing dramatically failure and complication
      rates for central venous port (CVP) placement. AIMS: The aim of this study was to
      determine the safety and efficacy of ultrasound-guided IJV CVP placement in
      elderly oncologic patients. METHODS: Between January 2013 and December 2015, 101
      elderly oncological patients underwent right IJV CVP placement under ultrasound
      guidance. The length of catheter introduction ranged from 18 to 21 cm.
      Intraoperative fluoroscopy (IF) was always performed intraoperatively. Chest X
      ray (CXR) was always performed 30 min after the end of the procedure. RESULTS:
      The morbidity rate was 1.98%; two arterial punctures were reported with one self
      limiting hematoma. Two patients (1.98%) had catheter misplacements, recognized by
      intraoperative IF. No patients (0%) experienced pneumothorax (PNX), confirmed at
      CXR. Patients were all discharged at maximum 6 h from the procedure. DISCUSSION:
      The risk of catheter misplacement, PNX, and arterial/nerve puncture remains
      present with this technique. Lower rates of catheter misplacement have been
      reported after right IJV puncture, probably for its straight vertical course. Our
      results are in accordance with literature (1 counter-lateral subclavian vein and
      1 counter-lateral internal jugular vein misplacements). All misplacements were
      detected intraoperatively. The PNX rates after cannulation of the IJV vary
      between 0.0 and 0.5%. We had no PNX occurrence. CONCLUSION: Ultrasonography (US)
      has improved safety and effectiveness of port system placements. While routine
      post-procedural CXR seems avoidable, IF should be considered mandatory.

PMID- 27896795
TI  - Intersession reliability of self-selected and narrow stance balance testing in
      older adults.
AB  - BACKGROUND: Despite the common practice of using force platforms to assess
      balance of older adults, few investigations have examined the reliability of
      postural screening tests in this population. AIM: We sought to determine the test
      retest reliability of self-selected and narrow stance balance testing with eyes
      open and eyes closed in healthy older adults. METHODS: Thirty older adults (>65
      years) completed 45 s trials of eyes open and eyes closed stability tests using
      self-selected and narrow stances on two separate days (1.9 +/- .7 days). Average
      medial-lateral center of pressure velocity was computed. RESULTS: The ICC results
      ranged from .74 to .86, and no significant systematic changes (P < .05) occurred
      between the testing sessions for any of the tests. The standard error of
      measurement ranged from 15.9 to 23.6%. DISCUSSION: Reliability estimates were
      similar between the two stances and visual conditions assessed. Slightly higher
      coefficients were identified for the self-selected stances compared to the narrow
      stances under both visual conditions; however, there were negligible differences
      between the sessions. The within subject session-to-session variability provides
      a basis for further research to consider differences between fallers and non
      fallers. CONCLUSION: Reliability for eyes open and closed balance testing using
      self-selected and narrow stances in older adults was established which should
      provide a foundation for the development of fall risk screening tests.

PMID- 27896796
TI  - Development and validation of a frailty index in the Longitudinal Aging Study
      Amsterdam.
AB  - BACKGROUND: Frailty is a state of increased vulnerability to adverse outcomes.
      The frailty index (FI), defined by the deficit accumulation approach, is a
      sensitive instrument to measure levels of frailty, and therefore important for
      longitudinal studies of aging. AIMS: To develop an FI in the Longitudinal Aging
      Study Amsterdam (LASA), and to examine the predictive validity of this FI for 19
      year mortality. METHODS: LASA is an ongoing study among Dutch older adults, based
      on a nationally representative sample. A 32-item FI (LASA-FI) was developed at
      the second LASA measurement wave (1995-1996) among 2218 people aged 57-88 years.
      An FI score between 0 and 1 was calculated for each individual. The LASA-FI
      included health deficits from the physical, mental and cognitive domain and can
      be constructed for most LASA measurement waves. Associations with 19-year
      mortality were assessed using Kaplan-Meier curves and Cox proportional hazards
      models. RESULTS: The mean LASA-FI score was 0.19 (SD = 0.12), with a 99% upper
      limit of 0.53. Scores were higher in women than men (women = 0.20, SD = 0.13 vs.
      men = 0.17, SD = 0.11, p < 0.001). The average age-related increase in the log
      transformed LASA-FI score was 3.5% per year. In a model adjusted for age and sex,
      the FI score was significantly associated with 19-year all-cause mortality (HR
      per 0.01 = 1.03, 95% CI 1.03-1.04, p < 0.001). DISCUSSION/CONCLUSIONS: The key
      characteristics of the LASA-FI were in line with findings from previous FI
      studies in population-based samples of older people. The LASA-FI score was
      associated with mortality and may serve as an internal and external reference
      value.

PMID- 27896797
TI  - A telephone-based intervention to promote physical activity during smoking
      cessation: a randomized controlled proof-of-concept study.
AB  - Smoking and physical inactivity contribute to disproportionate disease burden
      among underserved adults. Telephone-based interventions (quitlines) are becoming
      the standard care for addressing smoking. There is increasing interest to
      determine whether quitlines can be utilized to administer interventions for other
      unhealthy behaviors. This study aims to examine the proof-of-concept and
      potential efficacy of a telephone-based behavioral counseling intervention to
      boost daily low-to-moderate physical activity among low-income, physically
      inactive smokers. Participants (N = 101) were randomized to receive 4 weeks of
      counseling prior to their smoking quit day that included either standard smoking
      cessation counseling (control) or the Step-up to Quit (SUTQ) intervention. SUTQ
      promoted daily walking to foster physical activity as a primary smoking urge
      management strategy and facilitate incremental increases in daily steps with the
      goal of achieving 7500 steps/day by the quit day in week 4. Exploratory
      structural equation modeling tested SUTQ effects on six measures of low-to
      moderate physical activity (primary outcome) and smoking cue reactivity
      (secondary outcome) simultaneously in a single multivariate model with
      controlling variables. The sample was 51 % female and 77 % African-American, with
      a mean age of 42.1 years (SD = 10.9). Compared to the control condition, SUTQ
      intervention was associated with greater physical activity at week 4 (b = 0.51, z
      = 1.71, p = 0.08), with between-group differences sustained at follow-up. At week
      4, the SUTQ group had higher 7-day mean steps/day (M = 7,207.25, SD = 4,276.03)
      than controls (M = 3,947.03, SD = 3,655.03) (t = 3.35; p < .01); and had more
      participants reach the >7500 steps/day goal (49% vs. 11 %, c2 = 10.78; p < .01),
      a difference that was sustained at 1-month follow-up (X2 = 9.04, p < .01) Effects
      of SUTQ treatment on cue reactivity were in the hypothesized direction but not
      significant (b = -0.29; z = -1.09, p = 0.27). To our knowledge, this is the first
      study to promote physical activity using telephone counseling in an underserved
      population of smokers known to have greater challenges with physical activity
      adoption and smoking cessation. The SUTQ approach suggests that integration of
      physical activity advice and support within the context of smoking cessation
      treatment has the potential to promote physical activity among smokers intending
      to quit.

PMID- 27896798
TI  - Applicability of acceptance and commitment therapy-based mobile app in depression
      nursing.
AB  - Due to the high burden of depression, new models and methods of mental healthcare
      need to be developed. Prior research has shown the potential benefits of using
      technology tools such as mobile apps as self-help or combined with psychological
      treatment. Therefore, professionals should acquaint themselves with evidence
      based apps to be able to use them with clients and guide the clients in their
      use. The purpose of this study was to explore how an acceptance and commitment
      therapy-based mobile app was perceived as a self-management tool among nurses,
      and how it could be applied in the prevention and treatment of depression and
      other mental health issues. Sixteen Finnish nurses undergoing depression nurse
      specialist education used the app for 5 weeks and participated in semistructured
      focus group interviews. Interviews were analyzed by qualitative content analysis.
      In general, the nurses found the app suitable as a self-management tool and
      identified three models of using it in clinical practice. Having used the app
      personally, the nurses were eager to take it into use with various client groups,
      especially in occupational health but also in the treatment of mental health
      problems. However, they also raised concerns about the effort needed in
      familiarizing oneself with the content and pointed out specific client groups for
      whom the benefits of the app should be carefully weighed against the potential
      risks. Despite the small sample size, the findings suggest that involving
      technology tools as part of the nurses' education could ease their adoption in
      clinical practice. The degree of professional support in the app use should be
      aligned to the severity of the mental health problems.

PMID- 27896800
TI  - Principal component analysis in the evaluation of osteoarthritis.
AB  - OBJECTIVES: The purpose of this study is to demonstrate advantages of principal
      component analysis (PCA) as a standardized procedure in the evaluation of
      osteoarthritis (OA) in a skeletal series to: (1) compute aggregate scores for
      joint complexes that accurately capture pathological expression, (2) reveal which
      variables describe the most sample variation in OA, (3) enable inter- and intra
      sample comparison of results, and (4) formulate predictive models from component
      based arthritic scores. MATERIALS AND METHODS: The sample (144 males, 145
      females) is drawn from a large skeletal cemetery collection of modern Europeans
      of known sex, age, and occupation. OA data was collected using standard ranked
      categorical scoring. PCA was conducted separately on lumbar spine, pelvis, and
      knee regions to generate composite OA scores from eigenequations of the first and
      second principal components (PC). RESULTS: Results demonstrate that as severity
      in OA increases, so does the distribution of OA within the joint surface. In each
      region, PCA produced the same general pattern with eburnation scoring driving
      significant changes in composite OA scores, representing earlier to later stages
      of cartilage degeneration. The distribution of arthritic traits determined by PCA
      produced an OA score that quantifies the expression of joint changes in varied
      biological joint structures from most moveable to least mobile, the final stage
      being joint fusion. OA scores are most highly variable in the lumbar region for
      both males and females, as compared to the pelvis and knee. CONCLUSIONS: PCA is a
      simple, non-parametric method of extracting relevant information from complex OA
      datasets and summarizes variation based on correlated multi-attributes to reveal
      a simplified structure of OA expression. Multivariate techniques like PCA should
      be used to describe discrete OA samples, and are useful to compute population
      specific representative measurements for idiopathic joint OA in a skeletal
      sample.

PMID- 27896801
TI  - From threat to gradual lifestyle changes: Iranians' experiences with chronic
      illnesses.
AB  - AIM: This study aimed to explore and describe the experience of making a healthy
      lifestyle change among the patients with chronic illness. BACKGROUND: Despite the
      existence of different evidence on the critical role of lifestyle in the
      prevention and management of chronic diseases, many people face challenges in
      terms of starting and maintaining a healthy lifestyle. METHODS: A descriptive
      qualitative study with in-depth semi-structured interviews was carried out in
      2015 in Iran. Thirty-four patients with common chronic illnesses were invited to
      the study using purposive sampling. The collected data were analysed by content
      analysis. FINDINGS: The main themes were: trying to remove the perceived threat,
      considering and trying to do physical activities, considering and planning for a
      healthy diet, striving to manage stress and having gradual acceptance of new
      habits and coping with them. LIMITATIONS: The participants were selected from
      among those with chronic illness. However, there is also a need to assess the
      family and healthcare providers' perspectives. CONCLUSION AND IMPLICATIONS FOR
      NURSING: The perceived threat of the disease plays an important role in the
      process of changing to a healthy lifestyle in Iranian with chronic illnesses. It
      is necessary for healthcare providers, especially nurses, to use this threat as a
      golden opportunity to accelerate changes in patients' behaviours. IMPLICATIONS
      FOR NURSING POLICY: Findings may help policy makers become aware of the need for
      nurses to create community-based nursing in Iran. Community nurses can remind
      patients of perceived threats to their health to motivate them for continued
      healthy behaviours. Therefore, nursing curricula should be revised and
      educational programs utilise a community-based health approach.

PMID- 27896802
TI  - A method to characterize the roughness of 2-D line features: recrystallization
      boundaries.
AB  - A method is presented, which allows quantification of the roughness of nonplanar
      boundaries of objects for which the neutral plane is not known. The method
      provides quantitative descriptions of both the local and global characteristics.
      How the method can be used to estimate the sizes of rough features and local
      curvatures is also presented. The potential of the method is illustrated by
      quantification of the roughness of two recrystallization boundaries in a pure Al
      specimen characterized by scanning electron microscopy.

PMID- 27896799
TI  - A Comparison of Sex Differences in Psychotropic Medication Use in Older People
      with Alzheimer's Disease in the US and Finland.
AB  - AIMS: Given the high prevalence of psychotropic medication use in people with
      dementia and the potential for different prescribing practices in men and women,
      our study aimed to investigate sex differences in psychotropic medication use in
      older adults with Alzheimer's disease (AD) living in the US and Finland. METHODS:
      We used data collected between 2005 and 2011 as part of the National Alzheimer's
      Coordinating Center (NACC) in the US, and Medication use and Alzheimer's disease
      (MEDALZ) cohorts in Finland. We evaluated psychotropic medication use
      (antidepressant, antipsychotic, anxiolytic, sedative, or hypnotic) in
      participants aged 65 years or older. We employed multivariable logistic
      regression adjusted for demographics, co-morbidities, and other medications to
      estimate the magnitude of the association (adjusted odds ratio [aOR] with 95%
      confidence intervals [CIs]) according to sex. RESULTS: We included 1099 NACC
      participants (502 [45.68%] men, 597 [54.32%] women), and 67,049 participants from
      the MEDALZ cohort (22,961 [34.24%] men, 44,088 [65.75%] women). Women were more
      likely than men to use psychotropic medications: US, 46.2% vs. 33.1%, p < 0.001;
      Finland, 45.3% vs. 36.1%, p < 0.001; aOR was 2.06 (95% CI 1.58-2.70) in the US
      cohort and 1.38 (95% CI 1.33-1.43) in the Finnish cohort. Similarly, of the
      different psychotropic medications, women were more likely to use antidepressants
      (aOR-US: 2.16 [1.44-3.25], Finland: 1.52 [1.45-1.58]) and anxiolytics (aOR-US:
      2.16 [1.83-3.96], Finland: 1.17 [1.13-1.23]) than men. CONCLUSION: Older women
      with AD are more likely to use psychotropic medications than older men,
      regardless of study population and country. Approaches to mitigate psychotropic
      medication use need to consider different prescribing habits observed in older
      women vs. men with AD.

PMID- 27896803
TI  - The effect of craniokinesis on the middle ear of domestic chickens (Gallus gallus
      domesticus).
AB  - The avian middle ear differs from that of mammalians and contains a tympanic
      membrane, one ossicle (bony columella and cartilaginous extra-columella), some
      ligaments and one muscle. The rim of the eardrum (closing the middle ear cavity)
      is connected to the neurocranium and, by means of a broad ligament, to the otic
      process of the quadrate. Due to the limited number of components in the avian
      middle ear, the possibilities of attenuating the conduction of sound seem to be
      limited to activity of the stapedius muscle. We investigate to what extent
      craniokinesis may impact the components of the middle ear because of the
      connection of the eardrum to the movable quadrate. The quadrate is a part of the
      beak suspension and plays an important role in craniokinesis. Micro-computed
      tomography was used to visualize morphology and the effect of craniokinesis on
      the middle ear in the domestic chicken (Gallus gallus domesticus). Both hens and
      roosters are considered because of their difference in vocalization capacity. It
      is hypothesized that effects, if present, of craniokinesis on the middle ear will
      be greater in roosters because of their louder vocalization. Maximal lower jaw
      depression was comparable for hens and roosters (respectively 34.1 +/- 2.6
      degrees  and 32.7 +/- 2.5 degrees ). There is no overlap in ranges of maximal
      upper jaw elevation between the sexes (respectively 12.7 +/- 2.5 degrees  and
      18.5 +/- 3.8 degrees ). Frontal rotation about the transversal quadrato
      squamosal, and inward rotation about the squamosal-mandibular axes of the
      quadrate were both considered to be greater in roosters (respectively 15.4 +/-
      2.8 degrees  and 11.1 +/- 2.5 degrees ). These quadrate rotations did not affect
      the columellar position or orientation. In hens, an influence of the quadrate
      movements on the shape of the eardrum could not be detected either; however,
      craniokinesis caused slight stretching of the eardrum towards the caudal rim of
      the otic process of the quadrate. In roosters, an inward displacement of the
      conical tip of the tympanic membrane of 0.378 +/- 0.21 mm, as a result of
      craniokinesis, was observed. This is linked to a flattening and slackening of the
      eardrum. These changes most likely go along with a deformation of the extra
      columella. Generally, in birds, larger beak opening is related to the intensity
      of vocalization. The coupling between larger maximal upper jaw lifting in
      roosters and the slackening of the eardrum suggest the presence of a passive
      sound attenuation mechanism during self-vocalization.

PMID- 27896804
TI  - Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort
      studies.
AB  - OBJECTIVE: To examine the 30-day risk of hospitalization with hyponatremia
      associated with carbamazepine, valproic acid (V), phenytoin (P), or topiramate
      (T) use compared to nonuse in the outpatient setting among older adults. METHODS:
      We conducted two population-based, retrospective cohort studies in Ontario,
      Canada, between 2003 and 2015 using administrative health care databases of older
      adults. The first study compared carbamazepine users to a propensity-score
      matched group of antiepileptic drug nonusers, whereas the second compared V-P-T
      users to a propensity-score matched group of antiepileptic nonusers. The primary
      outcome was hospitalization with hyponatremia within 30 days of an antiepileptic
      prescription. RESULTS: The baseline characteristics between matched groups were
      similar in both cohorts. Carbamazepine use versus nonuse was associated with a
      higher 30-day risk of hospitalization with hyponatremia (82/21,191 [0.39%] versus
      30/63,573 [0.05%]; relative risk [RR] 8.20, 95% confidence interval [CI] 5.40
      12.46). Similarly, V-P-T use versus nonuse was associated with a higher 30-day
      risk of hospitalization with hyponatremia (34/20,155 [0.17%] versus 26/40,310
      [0.06%]; RR 2.62, 95% CI 1.57-4.36). SIGNIFICANCE: Older adults prescribed
      carbamazepine and V-P-T have a higher risk of being hospitalized with
      hyponatremia compared to other adults with similar indicators of baseline health
      who were not prescribed antiepileptic drugs. Physicians should be mindful of this
      risk; when a patient presents to a hospital with symptomatic hyponatremia these
      drugs should be considered as potential causes.

PMID- 27896805
TI  - Key Elements of a Family Intervention for Schizophrenia: A Qualitative Analysis
      of an RCT.
AB  - Schizophrenia is a complex biopsychosocial condition in which expressed emotion
      in family members is a robust predictor of relapse. Not surprisingly, family
      interventions are remarkably effective and thus recommended in current treatment
      guidelines. Their key elements seem to be common therapeutic factors, followed by
      education and coping skills training. However, few studies have explored these
      key elements and the process of the intervention itself. We conducted a
      qualitative and quantitative analysis of the records from a pioneering family
      intervention trial addressing expressed emotion, published by Leff and colleagues
      four decades ago. Records were analyzed into categories and data explored using
      descriptive statistics. This was complemented by a narrative evaluation using an
      inductive approach based on emotional markers and markers of change. The most
      used strategies in the intervention were addressing needs, followed by coping
      skills enhancement, advice, and emotional support. Dealing with overinvolvement
      and reframing were the next most frequent. Single-family home sessions seemed to
      augment the therapeutic work conducted in family groups. Overall the intervention
      seemed to promote cognitive and emotional change in the participants, and
      therapists were sensitive to the emotional trajectory of each subject. On the
      basis of our findings, we developed a longitudinal framework for better
      understanding the process of this treatment approach.

PMID- 27896806
TI  - Nitric oxide synthase during early embryonic development in silkworm Bombyx mori:
      Gene expression, enzyme activity, and tissue distribution.
AB  - To elucidate the mechanism for embryonic diapause or the breakdown of diapause in
      Bombyx mori, we biochemically analyzed nitric oxide synthase (NOS) during the
      embryogenesis of B. mori. The gene expression and enzyme activity of B. mori NOS
      (BmNOS) were examined in diapause, non-diapause, and HCl-treated diapause eggs.
      In the case of HCl-treated diapause eggs, the gene expression and enzyme activity
      of BmNOS were induced by HCl treatment. However, in the case of diapause and non
      diapause eggs during embryogenesis, changes in the BmNOS activity and gene
      expressions did not coincide except 48-60 h after oviposition in diapause eggs.
      The results imply that changes in BmNOS activity during the embryogenesis of
      diapause and non-diapause eggs are regulated not only at the level of
      transcription but also post-transcription. The distribution and localization of
      BmNOS were also investigated with an immunohistochemical technique using
      antibodies against the universal NOS; the localization of BmNOS was observed
      mainly in the cytoplasm of yolk cells in diapause eggs and HCl-treated diapause
      eggs. These data suggest that BmNOS has an important role in the early embryonic
      development of the B. mori.

PMID- 27896808
TI  - The effects of cracks on the quantification of the cancellous bone fabric tensor
      in fossil and archaeological specimens: a simulation study.
AB  - Cancellous bone is very sensitive to its prevailing mechanical environment, and
      study of its architecture has previously aided interpretations of locomotor
      biomechanics in extinct animals or archaeological populations. However,
      quantification of architectural features may be compromised by poor preservation
      in fossil and archaeological specimens, such as post mortem cracking or
      fracturing. In this study, the effects of post mortem cracks on the
      quantification of cancellous bone fabric were investigated through the simulation
      of cracks in otherwise undamaged modern bone samples. The effect on both scalar
      (degree of fabric anisotropy, fabric elongation index) and vector (principal
      fabric directions) variables was assessed through comparing the results of
      architectural analyses of cracked vs. non-cracked samples. Error was found to
      decrease as the relative size of the crack decreased, and as the orientation of
      the crack approached the orientation of the primary fabric direction. However,
      even in the best-case scenario simulated, error remained substantial, with at
      least 18% of simulations showing a > 10% error when scalar variables were
      considered, and at least 6.7% of simulations showing a > 10 degrees  error when
      vector variables were considered. As a 10% (scalar) or 10 degrees  (vector)
      difference is probably too large for reliable interpretation of a fossil or
      archaeological specimen, these results suggest that cracks should be avoided if
      possible when analysing cancellous bone architecture in such specimens.

PMID- 27896807
TI  - FDG PET-CT imaging of therapeutic response in granulomatous lymphocytic
      interstitial lung disease (GLILD) in common variable immunodeficiency (CVID).
AB  - Common variable immunodeficiency (CVID) is the most common severe adult primary
      immunodeficiency and is characterized by a failure to produce antibodies leading
      to recurrent predominantly sinopulmonary infections. Improvements in the
      prevention and treatment of infection with immunoglobulin replacement and
      antibiotics have resulted in malignancy, autoimmune, inflammatory and
      lymphoproliferative disorders emerging as major clinical challenges in the
      management of patients who have CVID. In a proportion of CVID patients,
      inflammation manifests as granulomas that frequently involve the lungs, lymph
      nodes, spleen and liver and may affect almost any organ. Granulomatous
      lymphocytic interstitial lung disease (GLILD) is associated with a worse outcome.
      Its underlying pathogenic mechanisms are poorly understood and there is limited
      evidence to inform how best to monitor, treat or select patients to treat. We
      describe the use of combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron emission
      tomography and computed tomography (FDG PET-CT) scanning for the assessment and
      monitoring of response to treatment in a patient with GLILD. This enabled a
      synergistic combination of functional and anatomical imaging in GLILD and
      demonstrated a widespread and high level of metabolic activity in the lungs and
      lymph nodes. Following treatment with rituximab and mycophenolate there was
      almost complete resolution of the previously identified high metabolic activity
      alongside significant normalization in lymph node size and lung architecture. The
      results support the view that GLILD represents one facet of a multi-systemic
      metabolically highly active lymphoproliferative disorder and suggests potential
      utility of this imaging modality in this subset of patients with CVID.

PMID- 27896809
TI  - A2A-D2 receptor-receptor interaction modulates gliotransmitter release from
      striatal astrocyte processes.
AB  - Evidence for striatal A2A-D2 heterodimers has led to a new perspective on
      molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite
      the increasing recognition of astrocytes' participation in neuropsychiatric
      disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor
      signal transmission has never been explored. Here, we investigated the presence
      of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat
      striatum by confocal imaging; the effects of receptor activation were measured on
      the 4-aminopyridine-evoked release of glutamate from the processes. Confocal
      analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte
      processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by
      measuring the release of the gliotransmitter glutamate: D2 receptors inhibited
      the glutamate release, while activation of A2A receptors, per se ineffective,
      abolished the effect of D2 receptor activation. The synthetic D2 peptide
      VLRRRRKRVN corresponding to the receptor region involved in electrostatic
      interaction underlying A2A-D2 heteromerization abolished the ability of the A2A
      receptor to antagonize the D2 receptor-mediated effect. Together, the findings
      are consistent with heteromerization of native striatal astrocytic A2A-D2
      receptors that via allosteric receptor-receptor interactions could play a role in
      the control of striatal glutamatergic transmission. These new findings suggest
      possible new pathogenic mechanisms and/or therapeutic approaches to
      neuropsychiatric disorders.

PMID- 27896811
TI  - Measuring changes of manual ability with ABILHAND-Kids following intensive
      training for children with unilateral cerebral palsy.
AB  - AIM: ABILHAND-Kids is a parent-reported questionnaire measuring manual ability in
      children with cerebral palsy (CP). Its psychometric properties have been
      established, with the exception of responsiveness, which is examined here.
      METHOD: In this cohort study, 98 children (46 males, 52 females; range 6-19y,
      mean 11y, standard deviation [SD] 3.3y) with unilateral CP underwent three
      assessments of upper extremity function: at baseline (T1); after 80 to 90 hours
      of intensive training (T2); and at follow-up (T3). The responsiveness was
      analyzed using global, group (based on age and on Manual Ability Classification
      System [MACS] level), and individual approaches during two time periods (T1-T2
      and T2-T3). Effect size was used to quantify magnitude of changes. RESULTS: The
      global approach showed significant improvements between T1 and T2 (p<0.001) but
      not between T2 and T3 (p=0.222). In the group analyses, effect size and SRM
      demonstrated large changes in younger children (6-12y, n=52, mean change=1.06
      logit, effect size >0.8) and small changes in the older children (13-19y, n=46,
      mean change=0.71 logit, effect size >0.4). Children in MACS level II demonstrated
      larger changes than children in MACS level I or III. INTERPRETATION: The ABILHAND
      Kids exhibited responsiveness in detecting changes after intensive training.
      Therefore, this scale is potentially useful in assessing the functional status of
      children with unilateral CP in clinical trials.

PMID- 27896812
TI  - Completeness and correctness of cerebral palsy diagnoses in two health registers:
      implications for estimating prevalence.
AB  - AIM: To assess completeness and correctness of cerebral palsy (CP) diagnoses in
      the Cerebral Palsy Register of Norway (CPRN) and the Norwegian Patient Register
      (NPR), and to estimate CP prevalence. METHOD: Among 747 883 Norwegian residents
      born from 1996 to 2007, 2231 had a diagnosis of CP in the NPR while 1441 were
      registered in the CPRN. Children registered in the CPRN were considered to have a
      valid CP diagnosis. For those with a diagnosis of CP only in the NPR, two
      paediatricians reviewed the hospital records. The prevalence rate of CP with 95%
      confidence intervals (CI) was calculated on the basis of the combined data sets.
      RESULTS: One thousand three hundred and ninety-eight children were registered
      with a diagnosis of CP in both registers, 43 children were only registered in the
      CPRN, and 824 only in the NPR. The review of hospital records revealed that 464
      (59.5%) had CP. Thus, the NPR was 98% complete, and for 86% the diagnosis was
      correct. The completeness of the CPRN was 76%, while the diagnosis was considered
      correct for all children (100%). The resulting prevalence of CP was 2.5 (95% CI
      2.4-2.7) per 1000. INTERPRETATION: To gain accurate estimates of prevalence rates
      of CP, it is essential to combine data sources and to validate register data.

PMID- 27896810
TI  - Multiple pathways for elevating extracellular adenosine in the rat hippocampal
      CA1 region characterized by adenosine sensor cells.
AB  - Extracellular adenosine in the brain, which modulates various physiological and
      pathological processes, fluctuates in a complicated manner that reflects the
      circadian cycle, neuronal activity, metabolism, and disease states. The dynamics
      of extracellular adenosine in the brain are not fully understood, largely because
      of the lack of simple and reliable methods of measuring time-dependent changes in
      tissue adenosine distribution. This study describes the development of a
      biosensor, designated an adenosine sensor cell, expressing adenosine A1 receptor,
      and a genetically modified G protein. This biosensor was used to characterize
      extracellular adenosine elevation in brain tissue by measuring intracellular
      calcium elevation in response to adenosine. Placement of adenosine sensor cells
      below hippocampal slices successfully detected adenosine releases from these
      slices in response to neuronal activity and astrocyte swelling by conventional
      calcium imaging. Pharmacological analyses indicated that high-frequency
      electrical stimulation-induced post-synaptic adenosine release in a manner
      dependent on L-type calcium channels and calcium-induced calcium release.
      Adenosine release following treatments that cause astrocyte swelling is
      independent of calcium channels, but dependent on aquaporin 4, an astrocyte
      specific water channel subtype. The ability of ectonucleotidase inhibitors to
      inhibit adenosine release following astrocyte swelling, but not electrical
      stimulation, suggests that the former reflects astrocytic ATP release and
      subsequent enzymatic breakdown, whereas the latter reflects direct adenosine
      release from neurons. These results suggest that distinct mechanisms are
      responsible for extracellular adenosine elevations by neurons and astrocytes,
      allowing exquisite regulation of extracellular adenosine in the brain.

PMID- 27896813
TI  - Transcriptional and post-transcriptional regulation of histone variant H2A.Z
      during sea urchin development.
AB  - Histone variant H2A.Z promotes chromatin accessibility at transcriptional
      regulatory elements and is developmentally regulated in metazoans. We
      characterize the transcriptional and post-transcriptional regulation of H2A.Z in
      the purple sea urchin Strongylocentrotus purpuratus. H2A.Z depletion by antisense
      translation-blocking morpholino oligonucleotides during early development causes
      developmental collapse, in agreement with its previously demonstrated general
      role in transcriptional multipotency. During H2A.Z peak expression in 24-h
      embryos, endogenous H2A.Z 3' UTR sequences stabilize GFP mRNAs relative to those
      with SV40 3' UTR sequences, although the 3' UTR of H2A.Z does not determine the
      spatial distribution of H2A.Z transcripts during embryonic and postembryonic
      development. We elaborated an H2A.Z::GFP BAC reporter that reproduces embryonic
      H2A.Z expression. Genome-wide chromatin accessibility analysis using ATAC-seq
      revealed a cis-regulatory module (CRM) that, when deleted, causes a significant
      decline of the H2A.Z reporter expression. In addition, the mutation of a Sox
      transcription factor binding site motif and, more strongly, of a Myb motif cause
      significant decline of reporter gene expression. Our results suggest that an
      undetermined Myb-family transcription factor controls the transcriptional
      regulation of H2A.Z.

PMID- 27896814
TI  - Evaluation of swimming performance for fish passage of longnose dace Rhinichthys
      cataractae using an experimental flume.
AB  - The swimming performance of longnose dace Rhinichthys cataractae, the most widely
      distributed minnow (Cyprinidae) in North America, was assessed in relation to
      potential passage barriers. The study estimated passage success, maximum ascent
      distances and maximum sprint speed in an open-channel flume over a range of water
      velocities and temperatures (10.7, 15.3 and 19.3 degrees  C). Rhinichthys
      cataractae had high passage success (95%) in a 9.2 m flume section at mean test
      velocities of 39 and 64 cm s-1 , but success rate dropped to 66% at 78 cm s-1 .
      Only 20% of fish were able to ascend a 2.7 m section with a mean velocity of 122
      cm s-1 . Rhinichthys cataractae actively selected low-velocity pathways located
      along the bottom and corners of the flume at all test velocities and adopted
      position-holding behaviour at higher water velocities. Mean volitional sprint
      speed was 174 cm s-1 when fish volitionally sprinted in areas of high water
      velocities. Swimming performance generally increased with water temperature and
      fish length. Based on these results, fishways with mean velocities <64 cm s-1
      should allow passage of most R. cataractae. Water velocities >100 cm s-1 within
      structures should be limited to short distance (<1 m) and structures with
      velocities >=158 cm s-1 would probably represent movement barriers. Study results
      highlighted the advantages of evaluating a multitude of swimming performance
      metrics in an open-channel flume, which can simulate the hydraulic features of
      fishways and allow for behavioural observations that can facilitate the design of
      effective passage structures.

PMID- 27896816
TI  - Altered pharyngeal structure and dynamics among patients with cervical kyphosis.
AB  - OBJECTIVES/HYPOTHESIS: Deformities of the anterior cervical spine are an
      established cause of dysphagia. Whereas osteophytes and spinal fusion hardware
      have been reported to alter bolus flow and contribute to swallowing dysfunction,
      the relationship between abnormal spine curvature and swallowing dysfunction is
      not established. The purpose of this investigation was to evaluate the
      association between cervical kyphosis and objective measures of swallowing
      dysfunction on videofluoroscopy. STUDY DESIGN: Case-control study of patients
      presenting to tertiary dysphagia center. METHODS: All videofluoroscopic swallow
      studies (VFSS) performed at our institution, between August 1, 2014, and August
      1, 2015, were retrospectively reviewed to identify patients with abnormal
      cervical kyphosis, according to Cobb and Jackson angle measurements. Patients
      with kyphosis were age- and gender-matched to persons without kyphosis. VFSS and
      demographic parameters were collected and compared between groups. RESULTS:
      Thirty-six patients with cervical kyphosis exceeding two standard deviations (SD)
      beyond established age-specific normal ranges were identified. The mean age of
      the entire cohort was 61.6 (SD +/-19.1) years. Mean pharyngeal area was 3.34 cm2
      greater in kyphosis patients compared to controls (95% confidence interval [CI]:
      0.47-5.21 cm2 ; P = .0007). This was associated with increased hypopharyngeal
      transit time (0.57 seconds, 95% CI: 0.045-1.09 seconds, P = .034), and higher
      prevalence of penetration (P = .014). There was no significant difference in the
      pharyngeal constriction ratio (PCR), a surrogate measure of pharyngeal strength
      (P = .83). CONCLUSIONS: Patients with cervical spine kyphosis have a
      significantly dilated pharynx (P = .0007), elongated hypopharyngeal transit time
      (P = .034), and worsened penetration aspiration scores (P = .021). Absence of a
      difference in PCR suggests adequate compensation as a group. LEVEL OF EVIDENCE:
      3b. Laryngoscope, 127:1832-1837, 2017.

PMID- 27896815
TI  - How and why are calcium currents curtailed in the skeletal muscle voltage-gated
      calcium channels?
AB  - Voltage-gated calcium channels represent the sole mechanism converting electrical
      signals of excitable cells into cellular functions such as contraction, secretion
      and gene regulation. Specific voltage-sensing domains detect changes in membrane
      potential and control channel gating. Calcium ions entering through the channel
      function as second messengers regulating cell functions, with the exception of
      skeletal muscle, where CaV 1.1 essentially does not function as a channel but
      activates calcium release from intracellular stores. It has long been known that
      calcium currents are dispensable for skeletal muscle contraction. However, the
      questions as to how and why the channel function of CaV 1.1 is curtailed remained
      obscure until the recent discovery of a developmental CaV 1.1 splice variant with
      normal channel functions. This discovery provided new means to study the
      molecular mechanisms regulating the channel gating and led to the understanding
      that in skeletal muscle, calcium currents need to be restricted to allow proper
      regulation of fibre type specification and to prevent mitochondrial damage.

PMID- 27896817
TI  - Lack of in vivo mutagenicity of 1,2-dichloropropane and dichloromethane in the
      livers of gpt delta rats administered singly or in combination.
AB  - 1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are possible causative
      agents associated with the development of cholangiocarcinoma in employees working
      in printing plant in Osaka, Japan. However, few reports have demonstrated an
      association between these agents and cholangiocarcinoma in rodent carcinogenicity
      studies. Moreover, the combined effects of these compounds have not been fully
      elucidated. In the present study, we evaluated the in vivo mutagenicity of 1,2
      DCP and DCM, alone or combined, in the livers of gpt delta rats. Six-week-old
      male F344 gpt delta rats were treated with 1,2-DCP, DCM or 1,2-DCP + DCM by oral
      administration for 4 weeks at the dose (200 mg kg-1 body weight 1,2-DCP and 500
      mg kg-1 body weight DCM) used in the carcinogenesis study performed by the
      National Toxicology Program. In vivo mutagenicity was analyzed by gpt
      mutation/Spi- assays in the livers of rats. In addition, gene and protein
      expression of CYP2E1 and GSTT1, the major enzymes responsible for the genotoxic
      effects of 1,2-DCP and DCM, were analyzed by quantitative polymerase chain
      reaction and western blotting. Gpt and Spi- mutation frequencies were not
      increased by 1,2-DCP and/or DCM in any group. Additionally, there were no
      significant changes in the gene and protein expression of CYP2E1 and GSTT1 in any
      group. These results indicated that 1,2-DCP, DCM and 1,2-DCP + DCM had no
      significant impact on mutagenicity in the livers of gpt delta rats under our
      experimental conditions. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27896818
TI  - Coupling immunity and programmed cell suicide in prokaryotes: Life-or-death
      choices.
AB  - Host-pathogen arms race is a universal, central aspect of the evolution of life.
      Most organisms evolved several distinct yet interacting strategies of anti
      pathogen defense including resistance to parasite invasion, innate and adaptive
      immunity, and programmed cell death (PCD). The PCD is the means of last resort, a
      suicidal response to infection that is activated when resistance and immunity
      fail. An infected cell faces a decision between active defense and altruistic
      suicide or dormancy induction, depending on whether immunity is "deemed" capable
      of preventing parasite reproduction and consequent infection of other cells. In
      bacteria and archaea, immunity genes typically colocalize with PCD modules, such
      as toxins-antitoxins, suggestive of immunity-PCD coupling, likely mediated by
      shared proteins that sense damage and "predict" the outcome of infections. In
      type VI CRISPR-Cas systems, the same enzyme that inactivates the target RNA might
      execute cell suicide, in a case of ultimate integration of immunity and PCD.

PMID- 27896819
TI  - Extracorporeal Membrane Oxygenation Outcomes After the Comprehensive Stage II
      Procedure in Patients With Single Ventricles.
AB  - Outcomes for extracorporeal membrane oxygenation (ECMO) have been described for
      patients with single ventricle physiology (SVP) undergoing cavopulmonary
      connection (Glenn procedure). An alternative surgical pathway for patients with
      SVP consists of an initial hybrid procedure followed by a comprehensive Stage II
      procedure. No data exist describing the outcomes of patients requiring ECMO after
      the comprehensive Stage II procedure. The goal of this study is to describe the
      outcomes for patients who required ECMO after the comprehensive Stage II
      procedure. Data from the Extracorporeal Life Support Organization (ELSO) registry
      from 2001 to 2015 for children undergoing the comprehensive Stage II procedure
      older than 3 months of age were retrospectively analyzed. Demographics and ECMO
      characteristics were recorded. A total of six children required ECMO support
      after the comprehensive Stage II procedure (2 males, 4 females). Four patients
      had the diagnosis of hypoplastic left heart syndrome and two patients had the
      diagnosis of an unbalanced atrioventricular septal defect. Bypass time was 242.8
      +/- 110.9 min and cross-clamp time was 91.2 +/- 46.2 min for the surgical
      procedure. Weight was 5.8 +/- 1.3 kg and age was 150.2 + 37.9 days at time of
      ECMO. ECMO duration was 276.0 +/- 218.1 h. Complications during the ECMO run
      included hemorrhage in four patients (67%), renal dysfunction in two patients
      (33%), and neurologic injury in two patients (33%). Four patients (67%) were
      discharged alive after ECMO decannulation. Despite being a much more extensive
      surgical procedure, the morbidity and mortality after ECMO in patients undergoing
      the comprehensive Stage II procedure are similar to those in patients undergoing
      the Glenn procedure. If needed, ECMO support is reasonable for patients after the
      comprehensive Stage II procedure.

PMID- 27896821
TI  - Clinical symptom tool that raises the index of suspicion for eosinophilic
      oesophagitis in adults and drives earlier biopsy for definitive diagnosis.
AB  - BACKGROUND: Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease
      (GERD) present with overlapping symptomatology and it is challenging to
      distinguish EoE from GERD clinically before endoscopy. AIM: To investigate the
      prognostic value of a set of clinical symptoms and laboratory values in patients
      with EoE and GERD. METHODS: In this prospective, single-centre, observational
      study, we compared clinical and laboratory data from 202 patients with EoE or
      GERD (10 relevant characteristics). Those characteristics showing potential
      significance in a univariate analysis were then included in a multivariate
      analysis. RESULTS: The set of 10 characteristics (10-marker set) was able to
      distinguish between EoE and GERD with good reliability (correct assignment, i.e.
      agreement with subsequent EGD, of 94.4%). Reduction of the set to the six
      statistically and clinically most relevant markers continued to give good
      reliability (88.9%), and further stepwise reduction led to four-marker sets
      comprising history of atopy, history of food impaction, proton pump inhibitor
      refractory symptoms and either immunoglobulin E or peripheral eosinophilia, with
      correct assignment rates of 91.3% and 85.1% respectively. CONCLUSIONS: We have
      developed a simple and easily applicable clinical/laboratory marker set that
      helps to distinguish EoE from GERD earlier in the treatment course, thus guiding
      the endoscopist to perform biopsies from the oesophagus to ensure the diagnosis.
      The application of the scoring system is expected to diagnose EoE earlier and
      avoiding delay of adequate treatment.

PMID- 27896820
TI  - PPARgamma targeted oral cancer treatment and additional utility of genomics
      analytic techniques.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists
      have been shown to have anti-proliferative, anti-angiogenic, and proapoptotic
      effects, leading to interest in their use as cancer therapeutics. Pioglitazone, a
      U.S. Food and Drug Administration-approved type II diabetes medication and
      PPARgamma agonist, may have a role in adjuvant head-and-neck squamous cell
      carcinoma treatment or prevention. Therefore, the purpose of this study was: 1)
      to treat oral cavity cancer cells with the PPARgamma activator, pioglitazone, to
      analyze gene expression changes; and 2) to compare those changes with our
      preexisting genomic data for development of hypothesis-driven additional basic
      and clinical studies. STUDY DESIGN: Prospective in vitro. METHODS: We utilized
      microarray technology, as well as OCPlus (Bioconductor open source software) and
      Ingenuity Pathway Analysis (Qiagen, Redwood City, CA), to analyze differential
      gene expression in tumor and pioglitazone-treated tumor cells on a genome-wide
      level to demonstrate the feasibility of such an approach and determine
      appropriate sample size for future investigations. RESULTS: We found that
      approximately 35 samples are required to adequately power future studies. We next
      discovered that pioglitazone significantly affects Inducible T-Cell Costimulator
      (iCOS)-Ligand for the T-cell-specific cell surface receptor ICOS (iCOSL) and type
      II diabetes mellitus pathways as a putative anti-cancer mechanism. CONCLUSION:
      Genome-wide analysis is possible for the exploration of differential pathway
      modulation and rapid hypothesis generation. Both inflammation and type II
      diabetes pathways were significantly altered and therefore might provide unique
      hypothesis-driven pharmacodynamic parameters for future in vitro or in vivo
      studies utilizing thiazolidinediones. These techniques could be applied to
      microarray or other high throughput data from a variety of hypothesis-generating
      research scenarios in otolaryngology (e.g., middle ear proteomics, sinus
      microbiome studies). LEVEL OF EVIDENCE: NA. Laryngoscope, 127:E124-E131, 2017.

PMID- 27896822
TI  - Simeprevir in combination with sofosbuvir in treatment-naive and -experienced
      patients with hepatitis C virus genotype 4 infection: a Phase III, open-label,
      single-arm study (PLUTO).
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of liver
      cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely
      in the Middle East, Egypt and Africa, and has also spread into Europe. There are
      limited data available regarding the use of direct-acting antiviral agents in HCV
      genotype 4-infected patients with cirrhosis. AIM: To evaluate in the phase III,
      open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of
      simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide
      analogue NS5B polymerase inhibitor) in treatment-naive and (peg)interferon +/-
      ribavirin-experienced HCV genotype 4-infected patients, with or without
      compensated cirrhosis. METHODS: Adult patients with chronic HCV genotype 4
      infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily
      for 12 weeks. The primary efficacy endpoint was sustained virologic response 12
      weeks after the end of treatment (SVR12). Safety was also assessed. RESULTS:
      Forty patients received treatment; the majority were male (73%) and treatment
      experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All
      patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91
      100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients.
      No serious adverse events were reported and no patients discontinued study
      treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40
      (5%) patients. CONCLUSIONS: Treatment with simeprevir plus sofosbuvir for 12
      weeks resulted in SVR12 rates of 100% in treatment-naive and -experienced
      patients with HCV genotype 4 infection with or without compensated cirrhosis, and
      was well tolerated. [NCT02250807].

PMID- 27896823
TI  - Estimation of state occupancy probabilities in multistate models with dependent
      intermittent observation, with application to HIV viral rebounds.
AB  - In follow-up studies on chronic disease cohorts, individuals are often observed
      at irregular visit times that may be related to their previous disease history
      and other factors. This can produce bias in standard methods of estimation.
      Working in the context of multistate models, we consider a method of
      nonparametric estimation for state occupancy probabilities that adjusts for
      dependent follow-up through the use of inverse-intensity-of-visit weighted
      estimating functions and smoothing. The methodology is applied to the estimation
      of viral rebound probabilities in the Canadian Observational Cohort on HIV
      positive persons. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27896825
TI  - Is it time to reconsider lobectomy in low-risk paediatric thyroid cancer?
AB  - OBJECTIVE: Current guidelines recommend total thyroidectomy for nearly all
      children with well-differentiated thyroid cancer (WDTC). These guidelines,
      however, derive from older data accrued prior to current high-resolution imaging.
      We speculate that there is a subpopulation of children who may be adequately
      treated with lobectomy. DESIGN: Retrospective analysis of prospectively
      maintained database. PATIENTS: Seventy-three children with WDTC treated between
      2004 and 2015. MEASUREMENTS: We applied two different risk-stratification
      criteria to this population. First, we determined the number of patients meeting
      American Thyroid Association (ATA) 'low-risk' criteria, defined as disease
      grossly confined to the thyroid with either N0/Nx or incidental microscopic N1a
      disease. Second, we defined a set of 'very-low-risk' histopathological criteria,
      comprising unifocal tumours <=4 cm without predefined high-risk factors, and
      determined the proportion of patients that met these criteria. RESULTS: Twenty
      seven (37%) males and 46 (63%) females were included in this study, with a mean
      age of 13.4 years. Ipsilateral- and contralateral multifocality were identified
      in 27 (37.0%) and 19 (26.0%) of specimens. Thirty-seven (51%) patients had lymph
      node metastasis (N1a = 18/N1b = 19). Pre-operative ultrasound identified all
      cases with clinically significant nodal disease. Of the 73 patients, 39 (53.4%)
      met ATA low-risk criteria and 16 (21.9%) met 'very-low-risk' criteria. All 'very
      low-risk' patients demonstrated excellent response to initial therapy without
      persistence/recurrence after a mean follow-up of 36.4 months. CONCLUSIONS:
      Ultrasound and histopathology identify a substantial population that may be
      candidates for lobectomy, avoiding the risks and potential medical and
      psychosocial morbidity associated with total thyroidectomy. We propose a clinical
      framework to stimulate discussion of lobectomy as an option for low-risk
      patients.

PMID- 27896824
TI  - Patients with the worst outcomes after paracetamol (acetaminophen)-induced liver
      failure have an early monocytopenia.
AB  - BACKGROUND: Acute liver failure (ALF) is associated with significant morbidity
      and mortality. Studies have implicated the immune response, especially
      monocyte/macrophages as being important in dictating outcome. AIM: To investigate
      changes in the circulating monocytes and other immune cells serially in patients
      with ALF, relate these with cytokine concentrations, monocyte gene expression and
      patient outcome. METHODS: In a prospective case-control study in the Scottish
      Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients
      admitted with paracetamol-induced liver failure (POD-ALF), 10 patients with non
      paracetamol causes of ALF and 16 controls were recruited. The peripheral blood
      monocyte phenotype was analysed by flow cytometry, circulating cytokines
      quantified by protein array and monocyte gene expression array performed and
      related to outcome. RESULTS: On admission, patients with worst outcomes after POD
      ALF had a significant monocytopenia, characterised by reduced classical and
      expanded intermediate monocyte population. This was associated with reduced
      circulating lymphocytes and natural killer cells, peripheral cytokine patterns
      suggestive of a 'cytokine storm' and increased concentrations of cytokines
      associated with monocyte egress from the bone marrow. Gene expression array did
      not differentiate patient outcome. At day 4, there was no significant difference
      in monocyte, lymphocyte or natural killer cells between survivors and the
      patients with adverse outcomes. CONCLUSIONS: Severe paracetamol liver failure is
      associated with profound changes in the peripheral blood compartment,
      particularly in monocytes, related with worse outcomes. This is not seen in
      patients with non-paracetamol-induced liver failure. Significant monocytopenia on
      admission may allow earlier clarification of prognosis, and it highlights a
      potential target for therapeutic intervention.

PMID- 27896826
TI  - What is the preferred perioperative antibiotic choice and duration of use
      following major head and neck surgery?

PMID- 27896828
TI  - Addressing the occupational needs of refugees and asylum seekers.

PMID- 27896827
TI  - LEAPing through the looking glass: secondary analysis of the effect of skin test
      size and age of introduction on peanut tolerance after early peanut introduction.
AB  - BACKGROUND: In the Learning Early About Peanut Allergy (LEAP) study, early peanut
      introduction in high-risk 4- to 11-month-olds was associated with a significantly
      decreased risk of developing peanut allergy. However, the influences of key
      baseline high-risk factors on peanut tolerance are poorly understood. METHODS:
      Secondary analysis was conducted on the publically available LEAP dataset,
      exploring relationships between peanut tolerance, baseline peanut/egg
      sensitization, eczema severity/duration, age of introduction, gender, and race.
      RESULTS: A multiple logistic regression model predicting odds of successful oral
      food challenge (OFC) at 60 months noted higher odds with early introduction (OR
      9.2, P < 0.001, 95% CI 4.2-20.3), white race (OR 2.1, P = 0.04, 95% CI 1.1-3.9),
      and advancing age (OR 4.8, P = 0.04, 95% CI 1.1-20.8). Odds of peanut tolerance
      were lower with increasing peanut wheal size (OR 0.58, P < 0.001, 95% CI 0.46
      0.74), increased baseline SCORAD score (OR 0.98, P = 0.04, 95% CI 0.97-1), and
      increased kUA /l of egg serum IgE (sIgE) (OR 0.99, P = 0.04, 95% CI 0.98-1). The
      probability of peanut tolerance in the early introduction group was 83% vs 43% in
      the avoidance group with SPT wheal of <4 mm. The probability of a successful OFC
      was significantly higher with peanut introduction between 6 and 11 months than at
      4-6 months. Increasing eczema severity had limited impact on the probability of
      peanut tolerance in the early introduction arm. CONCLUSION: Increasing peanut
      wheal size predicted peanut tolerance only in the avoidance arm. Peanut
      introduction between 6 and 11 months of age was associated with the highest rates
      of peanut tolerance, questioning the 'urgency' of introduction before 6 months.

PMID- 27896829
TI  - Immunomodulatory and Immunosuppressive Roles of 1alpha,25(OH)2D3 in Autoimmune
      Diseases.
AB  - Autoimmune diseases are pathological conditions characterized by abnormal
      responses, accompanied by autoantibodies to self-molecules. The role of vitamin D
      in autoimmune diseases has increased significantly in the recent past from its
      functions in calcium and phosphate homoeostasis, and it is now involved in the
      regulations and proliferations of Th1 and Th17 lymphocyte. 1alpha,25(OH)2D3 is
      very important in ameliorations of inflammatory disorders arising from autoimmune
      diseases, but the mechanism by which this is performed is still a bone of
      contentions. This review aimed to highlight the existing facts about the roles of
      Vitamin D in the treatment and management of autoimmune diseases. An extensive
      online literature search was conducted using PubMed, MEDLINE and Scopus.
      Accumulated bodies of research evidence are available which demonstrates that
      Vitamin D has a very important part to play in the regulation of immune responses
      in autoimmune diseases. Some of the authors suggested that Vitamin D3 carry-out
      its immunosuppressive and immune modulatory action, through its actions on
      antigen-presenting cells and activated T and B cells with the help of Vitamin D
      receptors present on the each of these cells. Vitamin D supplementation assists
      in autoimmune disorders by making qualitative and quantitative changes in the
      immune system (downregulation of Th1 and upregulations of Th2 cells). This
      resulted in the body to be more tolerant of self and less likely to mount
      autoimmune responses.

PMID- 27896830
TI  - Vagal nerve endings in visceral pleura and triangular ligaments of the rat lung.
AB  - The inner thoracic cavity is lined by the parietal pleura, and the lung lobes are
      covered by the visceral pleura. The parietal and visceral plurae form the pleural
      cavity that has negative pressure within to enable normal respiration. The lung
      tissues are bilaterally innervated by vagal and spinal nerves, including sensory
      and motor components. This complicated innervation pattern has made it difficult
      to discern the vagal vs. spinal processes in the pulmonary visceral pleura. With
      and without vagotomy, we identified vagal nerve fibres and endings distributed
      extensively in the visceral pleura ('P'-type nerve endings) and triangular
      ligaments ('L'-type nerve endings) by injecting wheat germ agglutinin-horseradish
      peroxidase as a tracer into the nucleus of solitary tract or nodose ganglion of
      male Sprague-Dawley rats. We found the hilar and non-hilar vagal pulmonary
      pleural innervation pathways. In the hilar pathway, vagal sub-branches enter the
      hilum and follow the pleural sheet to give off the terminal arborizations. In the
      non-hilar pathway, vagal sub-branches run caudally along the oesophagus and
      either directly enter the ventral-middle-mediastinal left lobe or follow the
      triangular ligaments to enter the left and inferior lobe. Both vagi innervate:
      (i) the superior, middle and accessory lobes on the ventral surfaces that face
      the heart; (ii) the dorsal-rostral superior lobe; (iii) the dorsal-caudal left
      lobe; and (iv) the left triangular ligament. Innervated only by the left vagus
      is: (i) the ventral-rostral and dorsal-rostral left lobe via the hilar pathway;
      (ii) the ventral-middle-mediastinal left lobe and the dorsal accessory lobe that
      face the left lobe via the non-hilar pathway; and (iii) the ventral-rostral
      inferior lobe that faces the heart. Innervated only by the right vagus, via the
      non-hilar pathway, is: (i) the inferior (ventral and dorsal) and left (ventral
      only) lobe in the area near the triangular ligament; (ii) the dorsal-middle
      mediastinal left lobe; and (iii) the right triangular ligament. Other regions
      innervated with unknown vagal pathways include: (i) the middle lobe that faces
      the superior and inferior lobe; (ii) the rostral-mediastinal inferior lobe that
      faces the middle lobe; and (iii) the ventral accessory lobe that faces the
      diaphragm. Our study demonstrated that most areas that face the dorsal thoracic
      cavity have no vagal innervation, whereas the interlobar and heart-facing areas
      are bilaterally or unilaterally innervated with a left-rostral vs. right-caudal
      lateralized innervation pattern. This innervation pattern may account for the
      fact that the respiratory regulation in rats has a lateralized right-side
      dominant pattern.

PMID- 27896831
TI  - Anomerization reaction of bare and microhydrated d-erythrose via explicitly
      correlated coupled cluster approach. Two water molecules are optimal.
AB  - We present a comprehensive benchmark computational study which has explored a
      complete path of the anomerization reaction of bare d-erythrose involving a pair
      of the low-energy alpha- and beta-furanose anomers, the former of which was
      observed spectroscopically (Cabezas et al., Chem. Commun. 2013, 49, 10826). We
      find that the ring opening of the alpha-anomer yields the most stable open-chain
      tautomer which step is followed by the rotational interconversion of the open
      chain rotamers and final ring closing to form the beta-anomer. Our results
      indicate the flatness of the reaction's potential energy surface (PES)
      corresponding to the rotational interconversion path and its sensitivity to the
      computational level. By using the explicitly correlated coupled cluster CCSD(T)
      F12/cc-pVTZ-F12 energies, we determine the free energy barrier for the alpha
      furanose ring-opening (rate-determining) step as 170.3 kJ/mol. The question of
      the number of water molecules (n) needed for optimal stabilization of the
      erythrose anomerization reaction rate-determining transition state is addressed
      by a systematic exploration of the PES of the ring opening in the alpha-anomer
      (H2 O)n and various beta-anomer-(H2 O)n (n = 1-3) clusters using density
      functional and CCSD(T)-F12 computations. These computations suggest the lowest
      free energy barrier of the ring opening for doubly hydrated alpha-anomer,
      achieved by a mechanism that involves water-mediated multiple proton transfer
      coupled with the furanose C?O bond breakage. Among the methods used, the G4
      performed best against the CCSD(T)-F12 reference at estimating the ring-opening
      barrier heights for both the hydrated and bare erythrose conformers. Our results
      for the hydrated species are most relevant to an experimental study of the
      anomerization reaction of d-erythrose to be carried out in microsolvation
      environment. (c) 2016 Wiley Periodicals, Inc.

PMID- 27896832
TI  - Leaving foster or residential care: a participatory study of care leavers'
      experiences of health and social care transitions.
AB  - BACKGROUND: Young people in residential or foster care experience multiple
      transitions around their 18th birthday without the long term and consistent
      support from their family of origin that most of their peers can expect. We
      report a mixed methods qualitative study of transitions across health and social
      care services for children leaving care, providing narratives of what young
      people described as positive, and what they and professionals think might be
      improved. METHODS: Data were collected in participatory meetings and individual
      interviews between young people and researchers (n = 24) and individual
      interviews with practitioners (n = 11). In addition to discussion and interview
      techniques, we used pictorial and other participatory methods. Interviews were
      coded by three members of the team and differences resolved with a fourth. Our
      analysis draws on thematic and framework approaches. RESULTS: Health was rarely
      at the top of any young person's agenda, although gaps in health care and
      exceptional care were both described. Housing, financial support and education
      took priority. Young people and professionals alike emphasized the importance of
      workers prepared to go the extra mile; of young people being able to contact
      professionals; and professionals being able to contact one another. CONCLUSIONS:
      Policy and practice aspirations for care leavers recommend gradual change but
      transfer rather than transition continues to be described by care leavers. Our
      data support the need for transition as a long-term process, with children and
      young people having early opportunities to prepare for citizenship.

PMID- 27896833
TI  - Exploiting the aggregation properties of alpha-synuclein for diagnostic purposes.

PMID- 27896834
TI  - Histologic alterations in tetralogy of Fallot.
AB  - BACKGROUND: This study was performed to investigate the pre-existing histologic
      alterations at the time of complete repair in patients with tetralogy of Fallot
      (TOF) and evaluate their effects on the early postoperative outcomes. METHODS:
      Fourteen patients, seven with acyanotic TOF (SO2  > 90, group I) and seven with
      cyanotic TOF (SO2  < 90, group II), undergoing complete repair, were enrolled.
      Right ventricular biopsies were examined for cardiomyocyte injury and fibrosis by
      light microscopy and mitochondrial injury by electron microscopy. The association
      of the severity of histologic alterations and postoperative inotrope use,
      intensive care unit, and in-hospital stays were evaluated. RESULTS: Compared with
      group I, patients in group II had a higher inotrope score (p = 0.03) and longer
      intensive care unit (p = 0.01) and in-hospital stays (p = 0.04). Cardiomyocyte
      injury and mitochondrial damage scores were higher in group II (p = 0.01 and p =
      0.02, respectively). Fibrosis was detected in all specimens but was more severe
      in group II (p < 0.001). However, we could not demonstrate any correlation
      between histologic alterations and early surgical outcomes. The history of spell
      was significantly associated with worse early surgical outcomes (p < 0.05).
      CONCLUSIONS: Pre-existing cardiomyocyte injury accompanied by mitochondrial
      damage and fibrosis were more pronounced in cyanotic TOF patients. Early repair
      may prevent the development of histopathologic alterations in these patients.

PMID- 27896835
TI  - Contact sensitization to limonene and linalool hydroperoxides in Spain: a GEIDAC*
      prospective study.
AB  - BACKGROUND: Limonene and linalool are common fragrance terpenes widely used in
      cosmetic, household and hygiene products. Their primary oxidation products formed
      after air exposure, the hydroperoxides, have been recognized as important contact
      haptens. OBJECTIVES: To investigate the prevalence of contact allergy to
      hydroperoxides of limonene (Lim-OOHs) and hydroperoxides of linalool (Lin-OOHs)
      in Spain, and to define the optimal concentration for screening in consecutive
      patients. METHODS: Three different concentrations of Lim-OOHs (0.1%, 0.2% and
      0.3% pet.) and Lin-OOHs (0.25%, 0.5% and 1.0% pet.) were simultaneously tested in
      3639 consecutive patients at 22 departments of dermatology in Spain. RESULTS: Lim
      OOHs at 0.1%, 0.2% and 0.3% yielded positive patch test reactions in 1.4%, 3.4%
      and 5.1% of the tested patients, respectively; and Lin-OOHs at 0.25%, 0.5% and
      1.0% yielded positive reactions in 1.3%, 2.9% and 4.9% of the tested patients,
      respectively. Few irritant (1.5-1.9%) and doubtful reactions (0.4-0.5%) to both
      terpene hydroperoxides were registered at the highest concentrations tested.
      CONCLUSIONS: Lim-OOHs and Lin-OOHs can be considered as common causes of contact
      allergy, and their inclusion in an extended baseline patch test series therefore
      seems to be appropriate. The patch test preparations of Lim-OOHs 0.3% pet. and
      Lin-OOHs 1.0% pet. are useful tools for screening of contact sensitization.

PMID- 27896836
TI  - Radiosynthesis and biological evaluation of the new PDE10A radioligand [18
      F]AQ28A.
AB  - Cyclic nucleotide phosphodiesterase 10A (PDE10A) regulates the level of the
      second messengers cAMP and cGMP in particular in brain regions assumed to be
      associated with neurodegenerative and psychiatric diseases. A better
      understanding of the pathophysiological role of the expression of PDE10A could be
      obtained by quantitative imaging of the enzyme by positron emission tomography
      (PET). Thus, in this study we developed, radiolabeled, and evaluated a new PDE10A
      radioligand, 8-bromo-1-(6-[18 F]fluoropyridin-3-yl)-3,4-dimethylimidazo[1,5
      a]quinoxaline ([18 F]AQ28A). [18 F]AQ28A was radiolabeled by both nucleophilic
      bromo-to-fluoro or nitro-to-fluoro exchange using K[18 F]F-K2.2.2 -carbonate
      complex with different yields. Using the superior nitro precursor, we developed
      an automated synthesis on a Tracerlab FX F-N module and obtained [18 F]AQ28A with
      high radiochemical yields (33 +/- 6%) and specific activities (96-145 GBq.MUmol-1
      ) for further evaluation. Initially, we investigated the binding of [18 F]AQ28A
      to the brain of different species by autoradiography and observed the highest
      density of binding sites in striatum, the brain region with the highest PDE10A
      expression. Subsequent dynamic PET studies in mice revealed a region-specific
      accumulation of [18 F]AQ28A in this region, which could be blocked by
      preinjection of the selective PDE10A ligand MP-10. In conclusion, the data
      suggest [18 F]AQ28A is a suitable candidate for imaging of PDE10A in rodent brain
      by PET.

PMID- 27896837
TI  - CD6 and Linker of Activated T Cells are Potential Interaction Partners for T Cell
      Specific Adaptor Protein.
AB  - The T cell-specific adaptor protein (TSAd) contains several protein interaction
      domains, and is merging as a modulator of T cell activation. Several interaction
      partners for the TSAd proline-rich region and phosphotyrosines have been
      identified, including the Src and Tec family kinases lymphocyte-specific protein
      tyrosine kinase and interleukin 2-inducible T cell kinase. Via its Src homology 2
      (SH2) domain, TSAd may thus function as a link between these enzymes and other
      signalling molecules. However, few binding partners to the TSAd SH2 domain in T
      cells are hitherto known. Through the use of in silico ligand prediction, peptide
      spot arrays, pull-down and immunoprecipitation experiments, we here report novel
      interactions between the TSAd SH2 domain and CD6 phosphotyrosine (pTyr)629 and
      linker of activated T cells (LAT) pTyr171 , pTyr191 and pTyr226 .

PMID- 27896838
TI  - Children with medical complexity: a scoping review of interventions to support
      caregiver stress.
AB  - BACKGROUND: Caring for children with chronic and complex medical needs places
      extraordinary stress on parents and other family members. A scoping review was
      undertaken to identify and describe the full range of current interventions for
      reducing caregiver stress. METHODS: Applying a broad definition of caregiver
      stress, a systematic search of three scientific databases (CINAHL, Embase and
      Ovid Medline), a general internet search and hand searching of key peer-reviewed
      articles were conducted. Inclusion criteria were as follows: (i) published in
      English between 2004-2016; (ii) focused on familial caregivers, defined as
      parents, siblings or extended family; (iii) targeted children/youth with medical
      complexity between the ages of 1-24 years; and (iv) described an intervention and
      impact on caregiver stress. Data on type of intervention, study design and
      methods, measures and overall findings were extracted. RESULTS: Forty-nine
      studies were included from a list of 22 339 unique titles. Six domains of
      interventions were found: care coordination models (n = 23); respite care (n =
      8); telemedicine (n = 5); peer and emotional support (n = 6); insurance and
      employment benefits (n = 4); and health and related supports (n = 3). Across
      studies, there was a wide variety of designs, outcomes and measures used.
      CONCLUSIONS: Positive findings of reductions in caregiver stress were noted
      within an emerging body of evidence on effective interventions for families of
      children with medical complexity. A commonality across domains was a significant
      focus on streamlining services and reducing the burden of care related to varied
      pressures experienced, including time, finances, care needs and service access,
      among others. There was non-conclusive evidence however around which of the six
      identified intervention domains or combination thereof are most effective for
      reducing stress. These promising findings demonstrate that stress reduction is
      possible with the right support and that multiple interventions may be effective
      in reducing burdens of care experienced by families of children with medical
      complexity.

PMID- 27896840
TI  - Virtual angioscopy and 3D navigation of the aorta.
AB  - The objective of this study is to demonstrate the applicability of virtual
      angioscopy (VA) in different forms of aortic disease where the diagnosis is
      unclear or uncertain. Five cases are presented where VA helped to establish a
      correct diagnosis and to choose the best surgical strategy by providing an
      intuitive image of the aorta.

PMID- 27896841
TI  - Dental pain in the medical emergency department: a cross-sectional study.
AB  - The aim of this study was to examine the number of patients attending a medical
      emergency department (MED) with dental problems over a three-year period. This
      cross-sectional study was carried out as part of a service evaluation. Data were
      collected via a database search of patient attendances at the MED using free text
      and the 10th revision of the International Statistical Classification of Diseases
      and Related Health Problems (ICD-10) for oral and dental diagnoses. Data were
      analysed using descriptive statistics, t-test and chi-squared tests. Over the
      three-year period, there were 2504 visits to the MED for dental-related
      complaints, accounting for 0.7% of all attendances. The majority of patients were
      male (53.9%), with a mean age of 29 (s.d. 19.4) years for men, and 32 (s.d. 19.7)
      years for females. The mean index of multiple deprivation per cent rank was
      35.0%. The most common diagnosis was unspecified dental disorder. Ten per cent of
      dental attendances to MED were repeat attendances by the same patients. In
      conclusion, patient attendances at MED for dental problems account for 0.7% of
      all attendances. MED may not be the most appropriate place for these patients to
      attend, in terms of care pathways, and also for economic reasons. The reasons why
      patients attend MED for dental problems clearly warrant further research.

PMID- 27896839
TI  - Dopamine elevates and lowers astroglial Ca2+ through distinct pathways depending
      on local synaptic circuitry.
AB  - Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca2+
      rises, the dopamine sensitivity of astroglia in situ and its physiological roles
      remain unknown. To minimize effects of experimental manipulations on astroglial
      physiology, here we monitored Ca2+ in cells connected via gap junctions to
      astrocytes loaded whole-cell with cytosolic indicators in area CA1 of acute
      hippocampal slices. Aiming at high sensitivity of [Ca2+ ] measurements, we also
      employed life-time imaging of the Ca2+ indicator Oregon Green BAPTA-1. We found
      that dopamine triggered a dose-dependent, bidirectional Ca2+ response in stratum
      radiatum astroglia, a jagged elevation accompanied and followed by below-baseline
      decreases. The elevation depended on D1/D2 receptors and engaged intracellular
      Ca2+ storage and removal whereas the dopamine-induced [Ca2+ ] decrease involved
      D2 receptors only and was sensitive to Ca2+ channel blockade. In contrast, the
      stratum lacunosum moleculare astroglia generated higher-threshold dopamine
      induced Ca2+ responses which did not depend on dopamine receptors and were
      uncoupled from the prominent inhibitory action of dopamine on local perforant
      path synapses. Our findings thus suggest that a single neurotransmitter-dopamine
      could either elevate or decrease astrocyte [Ca2+ ] depending on the receptors
      involved, that such actions are specific to the regional neural circuitry and
      that they may be causally uncoupled from dopamine actions on local synapses. The
      results also indicate that [Ca2+ ] elevations commonly detected in astroglia can
      represent the variety of distinct mechanisms acting on the microscopic scale.
      GLIA 2017;65:447-459.

PMID- 27896842
TI  - IL-12B Gene Polymorphisms and IL-12 p70 Serum Levels Among Patients with
      Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different
      polymorphisms in cytokine genes play a pathogenic role. IL-12 is now recognized
      as a critical cytokine in terms of regulating the balance between Th1 and Th2
      cells. We investigated the role of single nucleotide polymorphisms (SNPs)
      (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL-12B gene in the genetic
      susceptibility to RA and in the severity of the disease. Six hundred and thirty
      four Caucasian RA patients and 341 healthy matched controls were studied using
      PCR-RFLP method and high-resolution melting analysis. Concentration of IL-12
      cytokine level in serum was evaluated using ELISA. The genotype frequency did not
      deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype
      were statistically higher in patients with RA compared with the healthy control
      group in both codominant and recessive models (P = 0.037; P = 0.04,
      respectively). The frequency of rs3212227 C allele also showed similar tendency
      (P = 0.07). IL-12 level in serum was significantly higher in RA group compared
      with control (P < 0.0001). We observed that increased IL-12 serum level was
      correlated with higher number of tender and swollen joints, ExRA presence and
      higher levels of haemoglobin, CRP and PLT. Also higher IL-12 level in serum was
      observed within RA patients with hypertension. Present findings indicated that IL
      12p40 + 1188A/C polymorphism as well as IL-12p70 protein levels may be associated
      with RA in the Polish population.

PMID- 27896843
TI  - Impact of Clinical Presentation on Early Vascular Healing After Bioresorbable
      Vascular Scaffold Implantation.
AB  - BACKGROUND: Optimal strut coverage and early vascular healing are important
      factors to reduce the risk of stent thrombosis. Data on early vascular healing
      with the new bioresorbable vascular scaffolds (BVS) are lacking. Further, healing
      response after BVS implantation in different clinical presentation has not been
      fully investigated. METHODS AND RESULTS: We assessed with optical coherence
      tomography (OCT) the early vascular response to BVS implantation in 26
      consecutive patients presenting with acute coronary syndrome (ACS) or stable
      angina (SA). Images from 16 BVSs (17,166 struts) in ACS patients and 17 BVSs
      (23,045 struts) in SA patients were analyzed. The mean implanted BVS diameter and
      length was 3.1 +/- 0.4 mm and 20.4 +/- 5.8 mm. At mean 47.6 +/- 6.3 days, overall
      99% of BVS struts were covered. There were no differences between ACS and SA on
      the amount of tissue coverage per strut (0.09 +/- 0.02 mm vs. 0.09 +/- 0.01 mm; P
      = 0.86, respectively) and lumen area stenosis (24.2 +/- 19.3% vs. 22.3 +/- 22.0%;
      P = 0.78, respectively). However, a numerically higher proportion of protruding
      (ACS 1.2 +/- 2.7%; SA 4.2 +/- 6.5%; P = 0.11) and malapposed (ACS 0.4 +/- 0.5%;
      SA 2.4 +/- 5.8%; P = 0.18) struts were observed in SA compared to ACS, with
      trendy better healing score in ACS (1.87 +/- 1.67 vs. 5.28 +/- 7.28, P = 0.08).
      CONCLUSION: Early after BVS implantation almost complete scaffold strut coverage
      without any thrombi was observed by OCT, independent by the clinical presentation
      at index coronary intervention. However, BVS in ACS lesions were associated with
      easier strut penetration and a trendy better healing score compared with SA.

PMID- 27896844
TI  - Unicuspid tricuspid valve.

PMID- 27896845
TI  - STAT3 down-regulation induces mitochondria-dependent G2/M cell cycle arrest and
      apoptosis in oesophageal carcinoma cells.
AB  - STAT3 is persistently activated in a wide variety of human tumours, and aberrant
      STAT3 activity promotes tumour growth, invasion and metastasis. To explore STAT3
      down-regulation in human oesophageal cancer cells, cell proliferation, apoptosis
      and mitochondrial mechanisms were explored in oesophageal carcinoma TE1 cell
      cultures. We demonstrate for the first time that STAT3 down-regulation by RNAi is
      sufficient to inhibit oesophageal cancer cell proliferation inducing cell
      apoptosis. Further, we demonstrate that mitochondrial transmembrane potential is
      impaired thereby leading to collapsed mitochondrial membrane potential, abnormal
      mitochondrial membrane depolarization, nuclear DNA fragmentation and cell cycle
      G2/M arrest under the conditions of STAT3 down-regulation. Thus, our results
      suggest that STAT3 inhibition is a valid approach to induce oesophageal carcinoma
      cell mitochondrial-dependent apoptosis in therapeutic strategies against
      oesophageal cancers.

PMID- 27896846
TI  - International study of medical school learning environments and their
      relationship with student well-being and empathy.
AB  - OBJECTIVE: To assess whether favourable perceptions of the learning environment
      (LE) were associated with better quality of life, less burnout and more empathy
      across three undergraduate medical education programmes in Israel, Malaysia and
      China. METHODS: Cross-sectional surveys were administered at the end of the 2013
      2014 academic year at three medical schools: Technion American Medical Students
      Program (TAMS) in Israel, Perdana University-Royal College of Surgeons in Ireland
      School of Medicine (PURCSI) in Malaysia and Peking Union Medical College (PUMC)
      in China. LE perceptions were assessed using the Johns Hopkins Learning
      Environment Scale (JHLES). Well-being was assessed using validated items for
      quality of life and the depersonalisation and emotional exhaustion domains of
      burnout. The 20-item Jefferson Empathy Scale assessed empathy. Statistical
      analyses included bivariate regressions and multivariate regressions that
      adjusted for gender, school, class year and perceived academic rank. RESULTS:
      Overall, 400/622 (64.3%) students responded, with the following rates by site:
      TAMS 92/121 (76.0%), PURCSI 160/198 (80.1%) and PUMC 148/303 (48.8%). In
      multivariate models, favourable overall LE perceptions were associated with
      higher odds of good quality of life (odds ratio [OR], 3.2; 95% confidence
      interval [CI], 1.8-5.8; p < 0.001) and lower odds of emotional exhaustion (OR,
      0.34; 95% CI, 0.24-0.50; p < 0.001) and depersonaliation (OR, 0.30; 95% CI, 0.24
      0.37; p = 0.001). 'Community of Peers', one of seven factors in the JHLES, was
      the only one to be independently associated with better quality of life and less
      emotional exhaustion and depersonalisation. After adjusting for covariates, there
      was not a statistically significant association between overall LE and empathy
      (OR, 1.4; 95% CI, 0.91-2.2; p = 0.12). CONCLUSIONS: Students' LE perceptions are
      closely associated with their well-being, and fostering peer community may hold
      promise for enhancing quality of life and protecting against burnout. Across
      these three settings, LE and empathy were not closely related, suggesting that
      any influence of learning environment on empathy would be modest.

PMID- 27896847
TI  - A case of leucocytoclastic vasculitis as a complication of IgG4-related skin
      disease.

PMID- 27896848
TI  - Composite endpoints and the distortion of risk-benefit analysis.

PMID- 27896849
TI  - Cytoplasmic MSH2 immunoreactivity in a patient with Lynch syndrome with an EPCAM
      MSH2 fusion.
AB  - AIMS: Immunohistochemistry for mismatch repair (MMR) proteins is being
      increasingly used to examine MMR status in tumours. The aim of the present
      article was to report the case of a colon cancer patient with Lynch syndrome who
      showed unusual cytoplasmic MMR protein localization. METHODS AND RESULTS:
      Histologically, the colon cancer was diagnosed as medullary carcinoma associated
      with prominent tumour-infiltrating lymphocytes and a Crohn's-like reaction.
      Immunohistochemistry revealed cytoplasmic and nuclear expression of MSH2 in non
      neoplastic cells, and exclusively cytoplasmic expression in tumour cells. MSH6
      expression was nuclear in non-neoplastic cells, but was lost in tumour cells.
      Nuclear expression of MLH1 and PMS2 was retained in both non-neoplastic and
      tumour cells. The tumour was microsatellite instability-high, which is indicative
      of defective MMR function. A subsequent germline mutation analysis identified a
      genomic deletion spanning the 3' region of EPCAM and the 5' region of MSH2,
      resulting in an in-frame fusion of EPCAM and MSH2. CONCLUSIONS: The unusual
      cytoplasmic immunoreactivity of MSH2 was considered to be attributable to the non
      functional EPCAM-MSH2 fusion product. The present case illustrates that not only
      loss of expression, but also abnormal localization, of MMR proteins is indicative
      of a defective MMR system.

PMID- 27896850
TI  - Zebrafish larva as a reliable model for in vivo assessment of membrane remodeling
      involvement in the hepatotoxicity of chemical agents.
AB  - The easy-to-use in vivo model, zebrafish larva, is being increasingly used to
      screen chemical-induced hepatotoxicity, with a good predictivity for various
      mechanisms of liver injury. However, nothing is known about its applicability in
      exploring the mechanism called membrane remodeling, depicted as changes in
      membrane fluidity or lipid raft properties. The aim of this study was, therefore,
      to substantiate the zebrafish larva as a suitable in vivo model in this context.
      Ethanol was chosen as a prototype toxicant because it is largely described, both
      in hepatocyte cultures and in rodents, as capable of inducing a membrane
      remodeling leading to hepatocyte death and liver injury. The zebrafish larva
      model was demonstrated to be fully relevant as membrane remodeling was maintained
      even after a 1-week exposure without any adaptation as usually reported in
      rodents and hepatocyte cultures. It was also proven to exhibit a high sensitivity
      as it discriminated various levels of cytotoxicity depending on the extent of
      changes in membrane remodeling. In this context, its sensitivity appeared higher
      than that of WIF-B9 hepatic cells, which is suited for analyzing this kind of
      hepatotoxicity. Finally, the protection afforded by a membrane stabilizer,
      ursodeoxycholic acid (UDCA), or by a lipid raft disrupter, pravastatin,
      definitely validated zebrafish larva as a reliable model to quickly assess
      membrane remodeling involvement in chemical-induced hepatotoxicity. In
      conclusion, this model, compatible with a high throughput screening, might be
      adapted to seek hepatotoxicants via membrane remodeling, and also drugs targeting
      membrane features to propose new preventive or therapeutic strategies in chemical
      induced liver diseases. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27896852
TI  - Efficient Functionalization of Additives at Supramolecular Material Surfaces.
AB  - Selective surface modification reactions can be performed on additives that are
      supramolecularly incorporated into supramolecular materials. Hereby, processing
      of the material, that regularly requires harsh processing conditions (i.e., the
      use of organic solvents and/or high temperatures), and functionalization can be
      decoupled. Moreover, high-resolution depth profiling by time-of-flight (ToF)
      secondary-ion mass spectrometry clearly shows distinct differences in surface and
      bulk material composition.

PMID- 27896851
TI  - Quantitating the lateral skin stiffness by a new and versatile electro-mechanical
      instrument. Preliminary studies.
AB  - BACKGROUND: A new electro-mechanical device for measuring the lateral stiffness
      of the skin is now available. It basically allows to recording the forces that
      the skin opposes to a lateral displacement (1-2 mm) of a pinching type movement.
      Preliminary assays of this device to various skin sites and an artificial
      substrate aimed at defining its major characteristics (sensitivity,
      reproducibility, variations according to skin site). METHODS: The calibration of
      the device (Khelometer(r) ) and assessment of its reproducibility were carried
      out through the use of elastometer substrates of various stiffness's. The device
      was then used, in vivo, at different skin sites (scalp, inner and outer forearms,
      cheeks) of 213 healthy Japanese women of various ages. The short-time effect of a
      hydrating regimen (7% glycerol) was recorded on the outer forearm. RESULTS: This
      new device offers an appreciable reproducibility in vitro and in vivo
      (coefficient of variation of 2-4% and 5-14%, respectively). Unlike other
      biophysical methods, the Khelometer(r) can be easily applied onto the human scalp
      that shows a higher stiffness than the two other skin sites, increasing with age
      and presence of alopecia. In all the three studied skin sites, the impact of age
      leads to significantly higher lateral skin stiffness (LSS, expressed as N/mm)
      values. The latter were found significantly different between the two sides of
      the forearms where the outer (sun-exposed) side showed statistically slightly
      higher LSS, than the unexposed inner side. LSS values found on cheeks (~0.5 N/mm)
      were about four times lower than those of the scalp (~2 N/mm) and about half
      those of forearms (~1 N/mm). The effect of a 7% glycerol based formula was
      recorded 20 min post application onto the forearm, leading to a slight drop in
      LSS (approx. 15%) as compared to a vehicle-applied skin site. CONCLUSION: These
      preliminary studies clearly indicate that this new device, applicable to any skin
      site, offers appreciable assets such as sensitivity and reproducibility.
      Accordingly, it appears as a new approach in the non-invasive biophysical
      measurements of the skin surface, in both advanced and applied research
      investigations.

PMID- 27896853
TI  - Melanomas vs. nevi in high-risk patients under long-term monitoring with digital
      dermatoscopy: do melanomas and nevi already differ at baseline?
AB  - BACKGROUND: What lesions to select for a most efficient dermatoscopic monitoring
      of patients with multiple nevi remains an unresolved issue. OBJECTIVE: To compare
      the grade of atypia of melanomas and nevi of the same patient at baseline.
      METHODS: Prospective observational study using 236 dermatoscopic baseline images
      (59 quartets from 59 patients, each including one melanoma detected during follow
      up and three nevi). Dermatologists (n = 26) were asked to assess the 'grade of
      dermatoscopic atypia' on a numerical scale and to identify the melanomas.
      RESULTS: On average, each dermatologist identified 24 of 59 melanomas (40%,
      range: 11-37). The number of correct picks was greater for dermatologists with
      moderate (mean: 28) or high (mean: 28) experience compared to beginners (mean 17;
      P < 0.001). In three of the 59 sets, none of the 26 dermatologists identified the
      melanoma. The mean grade of dermatoscopic atypia was 2.5 for nevi (95% CI: 2.4
      2.6) and 3.0 for melanomas (95% CI: 2.9-3.1, P < 0.001). LIMITATIONS: Rating
      dermatologists were informed that each quartet of images included one melanoma
      creating substantial deviation from a real-life situation. CONCLUSION: A
      significant proportion of melanomas detected during follow-up cannot be
      differentiated from nevi at baseline. This necessitates the additional inclusion
      of less atypical lesions for monitoring.

PMID- 27896855
TI  - Enhancing CO2 Capture using Robust Superomniphobic Membranes.
AB  - Superomniphobic membranes for post-combustion CO2 capture are introduced.
      Concentrated aqueous amine solutions stay on the topmost part of the membranes,
      providing a large liquid/CO2 interface. Wetting of the membrane, which reduces
      the capture efficiency, is prevented. The CO2 capture rates using the chemically,
      mechanically, and thermally stable superomniphobic membranes are enhanced by up
      to 40% relative to commercial membranes.

PMID- 27896854
TI  - Decreased graft survival in liver transplant recipients of donors with positive
      blood cultures: a review of the United Network for Organ Sharing dataset.
AB  - Liver transplantation using blood culture positive donors (BCPD) has allowed a
      significant expansion of the donor pool. We aimed to characterize BCPD and assess
      the outcomes of BCPD liver transplant recipients. We retrieved data from the
      United Network for Organ Sharing (UNOS) registry on all adults who underwent
      primary, single-organ deceased-donor liver transplantation in the USA between
      2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the
      non-BCPD cohort. One-year graft and patient survival were compared between
      cohorts using Kaplan-Meier estimates and Cox models. A total of 28 961 patients
      were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely
      to be older, female, black, diabetic, hypertensive, and obese compared to non
      BCPD. Graft survival was significantly lower in BCPD recipients compared to non
      BCPD recipients (Kaplan-Meier, 0.85 vs. 0.87; P = 0.009). Results remained
      significant in propensity-matched analysis (P = 0.038). BCPD was independently
      associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01-1.20; P
      = 0.04). There were no significant differences in patient survival between study
      groups. BCPD was associated with decreased graft survival in liver transplant
      recipients. Studies are needed to identify subgroups of BCPD with the highest
      risk of graft failure and characterize the underlying pathogenic mechanisms.

PMID- 27896856
TI  - Graphene-Based Biosensors: Going Simple.
AB  - The main properties of graphene derivatives facilitating optical and electrical
      biosensing platforms are discussed, along with how the integration of graphene
      derivatives, plastic, and paper can lead to innovative devices in order to
      simplify biosensing technology and manufacture easy-to-use, yet powerful
      electrical or optical biosensors. Some crucial issues to be overcome in order to
      bring graphene-based biosensors to the market are also underscored.

PMID- 27896857
TI  - Former smoking and early and long-term graft outcome in renal transplant
      recipients: a retrospective cohort study.
AB  - Smoking is associated with unfavourable outcome in solid-organ transplant
      recipients. Nicotine may predispose to kidney injury by increasing oxidative
      stress. We hypothesized that former smoking negatively affects graft outcome in
      kidney transplant recipients and especially those with delayed graft function
      (DGF). We included adult recipients of a kidney transplant between 1 January 2003
      and 1 October 2015 at Ghent University Hospital and recorded outcomes until 31
      October 2015. We used Kaplan-Meier and multivariable Cox proportional hazard
      analysis to examine the relationship between former smoking at the time of
      transplantation and the incidence of 10-year graft loss with and without
      censoring for death in 1013 participants. We evaluated mean differences in eGFR
      over time by a random intercept and slope model, considering a linear time
      effect. After adjusting for potential confounders, a history of smoking was
      associated with an increased hazard of graft loss (adjusted hazard ratio (aHR)
      1.60; 95% CI: 1.17-2.17; P = 0.003) and death-censored graft loss (aHR 2.29; 95%
      CI: 1.41-3.72; P = 0.001). The linear time trend of eGFR was different between
      former and never smokers (P = 0.001). To conclude, former smoking exerts long
      lasting negative effects on graft outcome and this independent of DGF.

PMID- 27896858
TI  - Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in
      subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant:
      the randomized GALAXY study.
AB  - This prospective, randomized, phase 2 study in subjects with recurrent hepatitis
      C virus (HCV) genotype 1 postorthotopic liver transplant evaluated once-daily
      simeprevir 150 mg + sofosbuvir 400 mg, with and without ribavirin 1000 mg.
      Primary endpoint was proportion of subjects with week 12 sustained virologic
      response (SVR12). Thirty-three subjects without cirrhosis were randomized 1:1:1
      into three arms (stratified by genotype/subtype and Q80K): Arm 1, simeprevir +
      sofosbuvir + ribavirin, 12 weeks; Arm 2, simeprevir + sofosbuvir, 12 weeks; Arm
      3, simeprevir + sofosbuvir, 24 weeks; 13 additional subjects (two with cirrhosis,
      11 without cirrhosis) entered Arm 3. All 46 subjects received at least one dose
      of study drug; median age, 60 years; 73.9% male; 80.4% White; 71.7%
      genotype/subtype 1a [12 (36.4%) of these had Q80K]; median 4.5 years post
      transplant. Among randomized subjects, SVR12 was achieved by 81.8% in Arm 1, 100%
      in Arm 2, and 93.9% in Arm 3; two subjects did not achieve SVR12: one viral
      relapse (follow-up week 4; Arm 1) and one missing follow-up week 12 data. In
      total, five subjects had a serious adverse event, considered unrelated to
      treatment per investigator. Simeprevir exposure was increased relative to the
      nontransplant setting, but not considered clinically relevant. Simeprevir +
      sofosbuvir treatment, with or without ribavirin, was efficacious and well
      tolerated (ClinicalTrials.gov Identifier: NCT02165189).

PMID- 27896859
TI  - Paraneoplastic pityriasis rubra pilaris: case report and literature review.
AB  - Pityriasis rubra pilaris (PRP; MIM 173200) is an uncommon papulosquamous
      inflammatory dermatosis. Only a few cases of PRP associated with an underlying
      malignancy have been documented. We investigated a 59-year-old patient presenting
      with a fulminant form of PRP recalcitrant to systemic retinoid therapy, in whom
      the skin disease heralded a diagnosis of cholangiocarcinoma. We searched the
      MEDLINE database to find articles reporting on similar associations of PRP with
      malignancies. We identified 10 studies linking PRP and malignancies, but an
      association between PRP and cholangiocarcinoma has not yet been reported.

PMID- 27896860
TI  - Preference of goats (Capra hircus L.) for tanniniferous browse species available
      in semi-arid areas in Ethiopia.
AB  - The objectives were to determine browse species preference of goats using dry
      matter intake (DMI) as a proxy, to compare preference when offered in combination
      with polyethylene glycol (PEG) and to establish relationships between browse
      species intake and chemical compositional data. Air-dried leaves of Acacia
      etbaica, Cadaba farinosa, Capparis tomentosa, Dichrostachys cinerea, Dodonaea
      angustifolia, Euclea racemosa, Maerua angolensis, Maytenus senegalensis, Rhus
      natalensis and Senna singueana were used. Two cafeteria trials, each lasting 10
      days, were conducted using four local mature male goats of 2-2.5 years receiving
      a daily ration of grass hay (4% of body weight) and 200 g wheat bran. In trial 1,
      goats were offered 25 g of each browse species for a total of 30 min with intake,
      time spent on consumption and the number of visits to specific browse species
      recorded at 10-min intervals. In trial 2, the same procedure was followed except
      that 25 g of PEG 4000 was added to the daily wheat bran ration. Crude protein and
      neutral detergent fibre in browse species ranged from 69.0-245.5 to 159.8-560.6
      g/kg dry matter (DM) respectively. Total phenols and total tannins contents
      ranged between 3.7-70.6 and 2.5-68.1 mg tannic acid equivalent/g DM,
      respectively, and condensed tannins 1.7-18.4 Abs550 nm /g DM. Preference
      indicators measured in the first 10 min of browse species intake differed
      significantly among browse species and with PEG (p < 0.0001). Principal
      components explained 69.9% of the total variation in browse species DMI. Despite
      the high tannin levels, D. cinerea, R. natalensis and A. etbaica were the most
      preferred species regardless of PEG presence. Tannin levels at the observed
      browse species DMI did not determine preference, instead, preference appeared to
      be based on hemicellulose. Determining browse species preference is essential to
      exploit them to improve nutrient utilization and control parasites in goats.

PMID- 27896861
TI  - Cyclosporine A for severe atopic dermatitis in children. efficacy and safety in a
      retrospective study of 63 patients.
AB  - BACKGROUND: Cyclosporine A (CSA) is an immunosuppressant agent widely used in
      severe atopic dermatitis (AD). However, experience in children is limited.
      OBJECTIVES: To assess the efficacy and adverse events of CSA therapy in children.
      METHODS: Retrospective study of children with severe AD treated with CSA between
      January 2009 and December 2015. RESULTS: Data from 63 patients were collected.
      Mean age at the beginning of treatment was 8.4 years (+/-3.6). The median
      starting dose was 4.27 (+/-0.61) mg/kg/day. After 4 weeks of treatment, the
      outcome was excellent in 35% of cases, good in 29% and poor in 36% of the
      patients. The response was better in patients without eosinophilia (P < 0.05).
      The median duration of treatment was 4.6 months (range 1.5-21.6). Side-effects
      were frequent but mild, being more common in patients after longer treatment
      periods (P < 0.05). Mean time of follow-up was 19.4 months (+/-12.7). Prolonged
      remission (>6 months) was observed in 13 patients (20%). LIMITS: This is a
      retrospective review. The follow-up period is limited. CONCLUSIONS: Our data
      confirm that CSA is efficacious and acts rapidly in the majority of children with
      severe AD. CSA therapy can provide sustained remission in some patients. CSA
      seems to be well tolerated in children, but strict monitoring is mandatory.

PMID- 27896862
TI  - HCV and HEV recurrence after liver transplantation: one antiviral therapy for two
      viruses.

PMID- 27896863
TI  - One-Step Synthesis of Boron Nitride Quantum Dots: Simple Chemistry Meets Delicate
      Nanotechnology.
AB  - Herein, a conceptually new and straightforward aqueous route is described for the
      synthesis of hydroxyl- and amino-functionalized boron nitride quantum dots
      (BNQDs) with quantum yields (QY) as high as 18.3 % by using a facile bottom-up
      approach, in which a mixture of boric acid and ammonia solution was
      hydrothermally treated in one pot at 200  degrees C for 12 h. The functionalized
      BNQDs, with excellent photoluminescence properties, could be easily dispersed in
      an aqueous medium and applied as fluorescent probes for the detection of ferrous
      (Fe2+ ) and ferric (Fe3+ ) ions with excellent selectivity and low detection
      limits. The mechanisms for the hydrothermal reaction and fluorescence quenching
      were also simulated by using density functional theory (DFT), which confirmed the
      feasibility and advantages of this strategy. It provides a scalable and eco
      friendly method for preparation of BNQDs with good dispersability and could also
      be generalized to the synthesis of other 2D quantum dots and nanoplates.

PMID- 27896866
TI  - Re-conceptualizing the organ trade: separating "trafficking" from "trade" and the
      implications for law and policy.

PMID- 27896864
TI  - Pyroprotein-Based Electronic Textiles with High Stability.
AB  - Thermally reducible pyroprotein-based electronic textiles (e-textiles) are
      fabricated using graphene oxide and a pyroprotein such as cocoon silk and spider
      web without any chemical agents. The electrical conductivity of the e-textile is
      11.63 S cm-1 , which is maintained even in bending, washing, and temperature
      variation.

PMID- 27896865
TI  - Sensing at the Surface of Graphene Field-Effect Transistors.
AB  - Recent research trends now offer new opportunities for developing the next
      generations of label-free biochemical sensors using graphene and other two
      dimensional materials. While the physics of graphene transistors operated in
      electrolyte is well grounded, important chemical challenges still remain to be
      addressed, namely the impact of the chemical functionalizations of graphene on
      the key electrical parameters and the sensing performances. In fact, graphene -
      at least ideal graphene - is highly chemically inert. The functionalizations and
      chemical alterations of the graphene surface - both covalently and non-covalently
      - are crucial steps that define the sensitivity of graphene. The presence,
      reactivity, adsorption of gas and ions, proteins, DNA, cells and tissues on
      graphene have been successfully monitored with graphene. This review aims to
      unify most of the work done so far on biochemical sensing at the surface of a
      (chemically functionalized) graphene field-effect transistor and the challenges
      that lie ahead. The authors are convinced that graphene biochemical sensors hold
      great promise to meet the ever-increasing demand for sensitivity, especially
      looking at the recent progresses suggesting that the obstacle of Debye screening
      can be overcome.

PMID- 27896867
TI  - Collective Syntheses of Icetexane Natural Products Based on Biogenetic
      Hypotheses.
AB  - A divergent synthesis of 10 icetexane natural products based on a proposed
      biogenetic cationic ring expansion of a reduced carnosic acid derivative is
      described. Of these icetexanes, (+)-salvicanol, (-)-cyclocoulterone, (-)
      coulterone, (-)-obtusinone D, and (-)-obtusinone E have been synthesized for the
      first time. In addition, the hypothesis for the non-enzymatic biogenesis of
      benzo[1,3]dioxole natural products has been experimentally investigated.
      Additional experimental evidence for the abiotic formation of the methylenedioxy
      unit is provided, as photolysis of the quinone (+)-komaroviquinone resulted in
      the formation of the [1,3]dioxole-containing natural product (-)-cyclocoulterone
      and (+)-komarovispirone.

PMID- 27896868
TI  - Crohn's disease should be considered in children with inflammatory oral lesions.
AB  - : This systematic review presents the oral manifestations of paediatric Crohn's
      disease. Our review of 28 papers published from 2000 to 2015 showed that the
      prevalence of oral manifestations was 10-80%. Specific symptoms included mucosal
      tags, swelling of the lips, cheeks and gingiva, and cobblestoning mucosa.
      Nonspecific symptoms included aphthous-like ulcers, angular cheilitis, lip
      fissuring and gingivitis. CONCLUSION: The oral manifestations of Crohn's disease
      might precede intestinal inflammation or coincide with it. Crohn's disease should
      be considered in children with multiple oral manifestations and paediatric
      dentists, and gastroenterologists should be involved in their coordinated
      evaluation and follow-up.

PMID- 27896870
TI  - Tetracyclines and/or nicotinamide in blistering dermatosis.

PMID- 27896869
TI  - Identifying the location of epidermal growth factor-responsive element involved
      in the regulation of type IIb sodium-phosphate cotransporter expression in
      porcine intestinal epithelial cells.
AB  - Phosphate is an important mineral nutrient for both human and animals in growth
      and physiological functions; thus, much effort in the past has been made to
      clarify the mechanisms governing its absorption. Previous studies have found that
      epidermal growth factor (EGF) inhibits phosphate absorption in human intestinal
      cells via modulating the interaction of transcriptional factor c-myb with sodium
      phosphate cotransporter (NaPi-IIb) gene promoter. This finding provoked our
      interest in determining the effect of EGF on NaPi-IIb gene expression in
      intestinal cells of pigs and the location of EGF-responsive element in the gene
      promoter. Using quantitative PCR, it was observed that EGF significantly reduced
      NaPi-IIb gene expression in porcine intestinal epithelial IPEC-J2 cells.
      Transfection with a series of constructs that contain different lengths of the 5'
      flanking promoter region of the NaPi-IIb gene manifested that EGF-responsive
      element is located in the -1200 to -800 region. Further, c-myb was extracted from
      the cell nucleus of IPEC cells that were exposed to EGF or not via
      immunoprecipitation. The electrophoretic mobility shift assay showed a specific
      binding of transcription factor c-myb to labelled probes encompassing DNA
      sequence from -1092 to -1085 (-TCCAGTTG-). This protein-DNA complex was decreased
      with cells exposed to EGF and abrogated when c-myb was pre-incubated with
      excessive unlabelled competitive probes. Results from mutagenesis studies
      demonstrated that the c-myb-binding site is the EGF-responsive element involved
      in the regulation of NaPi-IIb expression. Identifying the location of EGF
      responsive element contributes to understanding mechanisms underlying EGF down
      regulated NaPi-IIb gene expression and provides a foundation for further
      investigating EGF-regulatory functions in phosphate absorption in pig intestine.

PMID- 27896871
TI  - The old reliables outperform new media in social marketing of Euromelanoma in
      Ireland.

PMID- 27896872
TI  - Sunbed use among Portuguese beach goers: a crave group while waiting sunbeds to
      be abolished.

PMID- 27896873
TI  - Identifying fallacious arguments in a qualitative study of antipsychotic
      prescribing in dementia.
AB  - BACKGROUND: Dementia can result in cognitive, noncognitive and behavioural
      symptoms which are difficult to manage. Formal guidelines for the care and
      management of dementia in the UK state that antipsychotics should only be
      prescribed where fully justified. This is because inappropriate use, particularly
      problematic in care-home settings, can produce severe side effects including
      death. The aim of this study was to explore the use of fallacious arguments in
      professionals' deliberations about antipsychotic prescribing in dementia in care
      home settings. Fallacious arguments have the potential to become unremarkable
      discourses that construct and validate practices which are counter to guidelines.
      METHODS: This qualitative study involved interviews with 28 care-home managers
      and health professionals involved in caring for patients with dementia.
      Potentially fallacious arguments were identified using qualitative content
      analysis and a coding framework constructed from existing explanatory models of
      fallacious reasoning. KEY FINDINGS: Fallacious arguments were identified in a
      range of explanations and reasons that participants gave for in answer to
      questions about initiating, reducing doses of and stopping antipsychotics in
      dementia. The dominant fallacy was false dichotomy. Appeal to popularity,
      tradition, consequence, emotion, or fear, and the slippery slope argument was
      also identified. CONCLUSIONS: Fallacious arguments were often formulated to
      present convincing cases whereby prescribing antipsychotics or maintaining
      existing doses (versus not starting medication or reducing the dose, for example)
      appeared as the only acceptable decision but this is not always the case. The
      findings could help health professionals to recognise and mitigate the effect of
      logic-based errors in decisions about the prescribing of antipsychotics in
      dementia.

PMID- 27896874
TI  - Five myths about variable selection.
AB  - Multivariable regression models are often used in transplantation research to
      identify or to confirm baseline variables which have an independent association,
      causally or only evidenced by statistical correlation, with transplantation
      outcome. Although sound theory is lacking, variable selection is a popular
      statistical method which seemingly reduces the complexity of such models.
      However, in fact, variable selection often complicates analysis as it invalidates
      common tools of statistical inference such as P-values and confidence intervals.
      This is a particular problem in transplantation research where sample sizes are
      often only small to moderate. Furthermore, variable selection requires computer
      intensive stability investigations and a particularly cautious interpretation of
      results. We discuss how five common misconceptions often lead to inappropriate
      application of variable selection. We emphasize that variable selection and all
      problems related with it can often be avoided by the use of expert knowledge.

PMID- 27896875
TI  - Disseminated cobblestone-like skin lumps in a newborn.

PMID- 27896876
TI  - Sites of recurrence in patients following clearance of psoriasis with biologic
      therapy.

PMID- 27896877
TI  - Flavonoids of Herba Epimedii Enhances Bone Repair in a Rabbit Model of Chronic
      Osteomyelitis During Post-infection Treatment and Stimulates Osteoblast
      Proliferation in Vitro.
AB  - Flavonoids are the active component of the Herba Epimedii (H. Epimedii), which is
      commonly used in Asia. This study is to investigate the effect of H. Epimedii on
      bone repair after anti-infection treatment in vivo. The bioactive-composition
      group of H. Epimedii (BCGE) contained four flavonoids with the total content of
      43.34%. Rabbits with chronic osteomyelitis in response to injection with
      Staphylococcus aureus were treated with BCGE of 242.70 mg/kg/day intragastrically
      after vancomycin-calcium sulphate treatment. Micro-computerd tomography (CT),
      morphology, blood biochemistry and osteocalcin levels were assessed for effect
      evaluation. In addition, the rat calvarial osteoblasts infected with S. aureus
      were treated with vancomycin and BCGE. Cell viability, alkaline phosphatase
      activity, bone morphogenetic protein 2, Runt-related transcription factor 2,
      osteoprotegerin, receptor activator of nuclear factor-kappaB ligand mRNA levels
      and protein expression were assessed. Our results indicated that BCGE promoted
      bone repair via increasing the bone mass, the volume of bone, promoting
      osteocalcin secretion after vancomycin-calcium sulfate treatment. BCGE enhanced
      the cell proliferation, by regulating bone morphogenetic protein 2, runt-related
      transcription factor 2, and osteoprotegerin/receptor activator of nuclear factor
      kappa-B ligand mRNA and protein expression to maintain the balance between bone
      formation and bone resorption. Therefore, BCGE is a potential adjuvant herbal
      remedy for the post-infection treatment of chronic osteomyelitis. Copyright (c)
      2016 John Wiley & Sons, Ltd.

PMID- 27896878
TI  - The relationship between leadership style and nurse-to-nurse incivility: turning
      the lens inward.
AB  - AIM: The aim of this study was to examine the impact of leadership styles on the
      reported rates of lateral hostility in nurses. BACKGROUND: Previous explanations
      of horizontal incivility point to oppressed group behaviour and socialisation of
      nurses. Leadership and organisational culture are known to have a profound impact
      on workplace behaviour, yet few studies have examined the relationship between
      leadership style and nurse-to-nurse incivility. METHODS: A survey was used to
      assess the perceived levels of incivility and the leadership styles experienced
      by 237 participants defined as 'staff nurses'. RESULTS: Transformational
      leadership style had the strongest correlation with low levels of incivility.
      Staff input and leader/staff teamwork also influence staff incivility.
      CONCLUSIONS: Leadership style is not a definitive factor of incivility, but
      leader behaviours impact the level of incivility between staff nurses. The
      relationship between leaders and staff and the empowerment of staff have the
      strongest impact on nurse incivility. IMPLICATIONS FOR NURSING MANAGEMENT: The
      factors found to correlate with incivility in this study are under the influence
      of nurse leaders. Relationships and interpersonal dynamics must be attended to.
      Leaders can also instil the structures known to foster nurse empowerment, which
      are discussed.

PMID- 27896879
TI  - We need a media platform perspective on alcohol marketing: a reply to Lobstein et
      al.

PMID- 27896880
TI  - A community-based cross-sectional survey of medication utilization among chronic
      disease patients in China.
AB  - OBJECTIVES: To determine medication use patterns and associated health outcomes
      in Chinese individuals with diabetes, hypertension or hyperlipidaemia. METHODS:
      This community-based cross-sectional study was done in a north China city of 300
      000 people. Participants were recruited by poster and phone call through
      Community Health Centres. Data were collected on 638 Chinese individuals.
      Interviews were done to screen for disease and health behaviours. Fasting blood
      was collected and analyzed. KEY FINDINGS: Participants' average age was 52 years.
      Self-reported prevalence of type 2 diabetes, hypertension and hyperlipidaemia was
      9.6, 29.9 and 20.5% respectively. Medication adherence was found among 88, 60 and
      81.5% of individuals with diabetes, hypertension and hyperlipidaemia
      respectively. Treatment success, as defined by medication adherence and treatment
      to goal was achieved by 21, 23 and 10% of diabetic, hypertensive and
      hyperlipidaemic patients. CONCLUSIONS: A large proportion of individuals with
      chronic disease in this China-based study were not being successfully treated,
      putting them at high risk for poor health outcomes. In this urban China setting,
      healthcare services need to be strengthened in order to achieve better treatment
      outcomes among chronic disease patients. It is recommended that community
      pharmacists contribute to improving these outcomes through participation in
      patient education, medication reconciliation and disease state management.

PMID- 27896881
TI  - Nympho-hymenal tear: a distinctive entity?

PMID- 27896882
TI  - Quality of claims and references found in Australian pharmacy journal
      advertisements.
AB  - OBJECTIVES: To evaluate the quality of pharmaceutical advertisement claims and
      supporting references in Australian pharmacy journals that target community
      pharmacists. METHODS: All full-page advertisements for a medicinal product, found
      in two Australian pharmacy journals from the year 2012 to 2015 were included.
      Advertisement claims and references were evaluated by claim type (unambiguous to
      immeasurable) and level of evidence (strong to irrelevant) in supporting
      references. KEY FINDINGS: Two hundred and ninety distinct advertisements and 598
      claims were identified, with a median of 2 claims per advertisement. Twenty-seven
      percent of claims were unambiguous, 40% were vague, 16% were emotive/immeasurable
      and 17% were non-clinical or other marketing claims. Half of all claims were
      referenced. Although 68% of unambiguous claims were referenced, 63% of those were
      supported by studies that were funded directly or indirectly by pharmaceutical
      companies. Only 13% of claims were supported with strong or moderate independent
      evidence. CONCLUSIONS: Pharmaceutical advertisements continue to present vague
      and emotive claims with little independent supporting evidence. Pharmacists need
      to be aware of these limitations when providing patient care. Increased awareness
      of this issue among pharmaceutical companies, Australian pharmaceutical journal
      publishers, regulators and pharmacists will assist in promoting optimised
      healthcare outcomes for the Australian public.

PMID- 27896883
TI  - Curcumin as a multifaceted compound against human papilloma virus infection and
      cervical cancers: A review of chemistry, cellular, molecular, and preclinical
      features.
AB  - Curcumin, the bioactive polyphenolic ingredient of turmeric, has been extensively
      studied for its effects on human papilloma virus (HPV) infection as well as
      primary and malignant squamous cervical cancers. HPV infections, especially those
      related to HPV 16 and 18 types, have been established as the leading cause of
      cervical cancer; however, there are also additional contributory factors involved
      in the etiopathogenesis of cervical cancers. Curcumin has emerged as having
      promising chemopreventive and anticancer effects against both HPV-related and
      nonrelated cervical cancers. In this review, we first discuss the biological
      relevance of curcumin and both its pharmacological effects and pharmaceutical
      considerations from a chemical point of view. Next, the signaling pathways that
      are modulated by curcumin and are relevant to the elimination of HPV infection
      and treatment of cervical cancer are discussed. We also present counter arguments
      regarding the effects of curcumin on signaling pathways and molecular markers
      dysregulated by benzo(a)pyrene (Bap), a carcinogen found in pathological cervical
      lesions of women who smoke frequently, and estradiol, as two important risk
      factors involved in persistent HPV-infection and cervical cancer. Finally,
      various strategies to enhance the pharmacological activity and pharmacokinetic
      characteristics of curcumin are discussed with examples of studies in
      experimental models of cervical cancer. (c) 2016 BioFactors, 43(3):331-346, 2017.

PMID- 27896885
TI  - Use of digital media for alcohol marketing: Response to Carah & Meurk.

PMID- 27896884
TI  - Contact allergy to preservatives: ESSCA* results with the baseline series, 2009
      2012.
AB  - BACKGROUND: Allergic contact dermatitis caused by biocides is common and causes
      significant patient morbidity. OBJECTIVE: To describe the current frequency and
      pattern of patch test reactivity to biocide allergens included in the baseline
      series of most European countries. METHODS: Data collected by the European
      Surveillance System on Contact Allergies (ESSCA) network between 2009 and 2012
      from 12 European countries were analysed. RESULTS: Methylisothiazolinone 0.2% aq.
      produced the highest prevalence of sensitization during the study period, with an
      overall prevalence of 4.5%. The mixture methylchloroisothiazolinone
      /methylisothiazolinone tested at 0.02% aq. followed closely, with 4.1% of
      positive reactions. Other preservatives with lower rates of sensitization, but
      still over 1%, include methyldibromo glutaronitrile (MDBGN) 0.5% pet. and
      iodopropynyl butylcarbamate (IPBC) 0.2% pet. Formaldehyde releasers and parabens
      yielded less than 1% positive reactions during the study period. Some regional
      differences in the prevalence of contact allergy to biocides among European
      countries were observed. CONCLUSIONS: Contact allergy to biocides is common
      throughout Europe, and regional differences could be explained by differences in
      exposure or characteristics of the population tested. Timely regulatory action
      for isothiazolinones is required. Although MDBGN is banned from cosmetics
      products since 2005, sensitization prevalence has not appeared to plateau. IPBC
      is an emerging allergen with an increasing prevalence over the last few years,
      and its inclusion in the European baseline series may be appropriate.

PMID- 27896886
TI  - Two-in-One: lambda-Orthogonal Photochemistry on a Radical Photoinitiating System.
AB  - An alkyne functional radical photoinitiator, 2-(4-(2-hydroxy-2
      methylpropanoyl)phenoxy)ethyl hex-5-ynoate, and evidence that both reactive
      moieties - the alkyne and the photoinitiator terminus - can be independently
      addressed with light of disparate wavelength (lambda-orthogonality) are
      introduced. The alkyne functionality is subjected to a visible light (420 nm)
      induced copper-catalyzed Huisgen reaction, which is employed for the selective
      functionalization of the initiator with a poly(ethylene glycol) (PEG) chain. This
      reaction proceeds completely lambda-orthogonal in the presence of the UV-reactive
      photoinitiating moiety. Conversely, it is demonstrated that the alkyne
      functionality of the photoinitiator is quantitatively orthogonal to UV
      irradiation emitted by the pulsing action of an excimer laser (351 nm, pulsed
      laser polymerization, PLP) and the generated radical species. In turn, the
      PEGylated initiator can readily be employed as a macrophotoinitiator during PLP.
      The introduced lambda-orthogonally addressable dual functional initiator can be
      used in a wide range of applications, including surface lithography and post
      synthetic modification of photocured materials.

PMID- 27896887
TI  - Benefits and tensions in delivering public health in community pharmacies - a
      qualitative study of healthy living pharmacy staff champions.
AB  - OBJECTIVE: Healthy Living Pharmacies (HLP) were introduced in the United Kingdom
      (UK) in a further attempt to deliver public health benefits in community pharmacy
      settings. Central to the initiative are staff trained as Healthy Living Champions
      (HLC) and this study sought to explore HLC perceptions of positive and negative
      aspect of their work and the wider scheme. METHODS: A qualitative study was
      undertaken with a purposive sample of HLCs working in pathfinder HCPs in the
      Sheffield area in 2014. Participants were recruited by email to either a focus
      group (n = 7) held at a training event or later semi-structured one-to-one
      interviews in pharmacies (n = 6). Four stages of interpretative phenomenological
      analysis were used to code and identify themes. KEY FINDINGS: Four main themes
      emerged relating to the positive workforce development impact HLPs had upon HLCs
      themselves and on perceived customer and patient engagement and benefits.
      Tensions were identified with existing commercial business demands and negative
      views overall of the pharmacy setting with a perceived lack of not only
      integration with other services but also awareness among the public and health
      care staff. HLCs felt empowered and more confident in initiating conversation
      about health issues with patients, but identified barriers relating to workload,
      a lack of time to perform their role, isolation, tensions with non-HLC staff and
      logistical barriers such as poor Internet access. CONCLUSIONS: Delivering public
      health activities through the HLC role in UK pharmacies is associated with
      several perceived benefits for different stakeholders, but may be threatened by
      well recognised barriers in UK pharmacies related to the commercial setting.

PMID- 27896888
TI  - Response of Narrow QRS Tachycardia to Late Coupled PVC: What Is the Mechanism?

PMID- 27896889
TI  - Haloperoxidase Mimicry by CeO2-x Nanorods Combats Biofouling.
AB  - CeO2-x nanorods are functional mimics of natural haloperoxidases. They catalyze
      the oxidative bromination of phenol red to bromophenol blue and of natural
      signaling molecules involved in bacterial quorum sensing. Laboratory and field
      tests with paint formulations containing 2 wt% of CeO2-x nanorods show a
      reduction in biofouling comparable to Cu2 O, the most typical biocidal pigment.

PMID- 27896890
TI  - Diterpenes as lead molecules against neglected tropical diseases.
AB  - Nowadays, neglected tropical diseases (NTDs) are reported to be present
      everywhere. Poor and developing areas in the world have received great attention
      to NTDs. Drug resistance, safety profile, and various challenges stimulate the
      search for alternative medications. Plant-based drugs are viewed with great
      interest, as they are believed to be devoid of side effects. Diterpenes, a family
      of essential oils, have showed attractive biological effects. A systematic review
      of the literature was carried out to summarize available evidences of diterpenes
      against NTDs. For this, databases were searched using specific search terms.
      Among the 2338 collected reports, a total of 181 articles were included in this
      review. Of them, 148 dealt with investigations using single organisms, and 33
      used multiple organisms. No mechanisms of action were reported in the case of 164
      reports. A total of 93.92% were related to nonclinical studies, and 4.42% and
      1.66% dealt with preclinical and clinical studies, respectively. The review
      displays that many diterpenes are effective upon Chagas disease, chikungunya,
      echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria,
      schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates
      against NTDs. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27896892
TI  - Recent advances in CKD and ESRD: A literature update.
AB  - The past year has seen interesting publications in the fields of chronic kidney
      disease and end stage renal disease. This review highlights some of these
      important papers and places their findings in the context of clinical care.

PMID- 27896891
TI  - STAT3 targeting by polyphenols: Novel therapeutic strategy for melanoma.
AB  - Melanoma or malignant melanocytes appear with the low incidence rate, but very
      high mortality rate worldwide. Epidemiological studies suggest that polyphenolic
      compounds contribute for prevention or treatment of several cancers particularly
      melanoma. Such findings motivate to dig out novel therapeutic strategies against
      melanoma, including research toward the development of new chemotherapeutic and
      biologic agents that can target the tumor cells by different mechanisms.
      Recently, it has been found that signal transducer and activator of transcription
      3 (STAT3) is activated in many cancer cases surprisingly. Different evidences
      supply the aspect that STAT3 activation plays a vital role in the metastasis,
      including proliferation of cells, survival, invasion, migration, and
      angiogenesis. This significant feature plays a vital role in various cellular
      processes, such as cell proliferation and survival. Here, we reviewed the
      mechanisms of the STAT3 pathway regulation and their role in promoting melanoma.
      Also, we have evaluated the emerging data on polyphenols (PPs) specifically their
      contribution in melanoma therapies with an emphasis on their
      regulatory/inhibitory actions in relation to STAT3 pathway and current progress
      in the development of phytochemical therapeutic techniques. An understanding of
      targeting STAT3 by PPs brings an opportunity to melanoma therapy. (c) 2016
      BioFactors, 43(3):347-370, 2017.

PMID- 27896893
TI  - An Acute Disseminated Encephalomyelitis-Like Illness in the Elderly: Neuroimaging
      and Neuropathology Findings.
AB  - INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a rare demyelinating
      disease of the central nervous system (CNS) that classically occurs in children
      and adolescents. It characteristically presents with acute inflammation,
      resulting in demyelination, often following an infectious disease. ADEM has been
      described in adult patients, but the incidence in the adult and especially
      elderly population is low. CASES: We describe five older adults (age 57 to 85)
      who presented with acute neurological symptoms. Three patients presented with an
      infectious illness preceding the event, 4 patients were encephalopathic, and
      oligoclonal bands (OCBs) were negative in all tested cases. The clinical scenario
      and imaging studies suggested alternative diagnoses, such as metastasis, primary
      CNS tumor, or stroke. Two patients had contrast enhancing lesions, two other
      patients had lesions with restricted diffusion on diffusion-weighted imaging.
      Neuropathologic diagnostic from biopsy or autopsy was eventually conclusive,
      showing perivascular zones of myelin loss with relative axonal sparing in all
      five cases. CONCLUSION: Each of these patients was found to have pathological
      findings of acute demyelination on tissue diagnosis, suggesting ADEM or ADEM-like
      disease. The initial presentation and imaging was pointing toward other
      diagnoses. Broad differential diagnosis is important, especially for older
      patients, and pathological proof might be warranted for a conclusive diagnosis.

PMID- 27896894
TI  - Perspectives of resettled African refugees on accessing medicines and pharmacy
      services in Queensland, Australia.
AB  - OBJECTIVES: The aim of this study was to explore the barriers to accessing
      medicines and pharmacy services among refugees in Queensland, Australia, from the
      perspectives of resettled African refugees. METHODS: A generic qualitative
      approach was used in this study. Resettled African refugees were recruited via a
      purposive snowball sampling method. The researcher collected data from different
      African refugee communities, specifically those from Sudanese, Congolese and
      Somalian communities. Participants were invited by a community health leader to
      participate in the study; a community health leader is a trained member of the
      refugee community who acts as a 'health information conduit' between refugees and
      the health system. Invitations were done either face-to-face, telephonically or
      by email. The focus groups were digitally recorded in English and transcribed
      verbatim by the researcher. Transcripts were entered into NVIVO(c) 11 and the
      data were analysed using inductive thematic analysis. KEY FINDINGS: Four focus
      groups were conducted between October and November 2014 in the city of Brisbane
      with African refugees, one with five Somali refugees, one with five Congolese
      refugees, one with three refugee community health leaders from South Sudan,
      Liberia and Eritrea and one with three refugee community health leaders from
      Uganda, Burundi and South Sudan. Eleven sub-themes emerged through the coding
      process, which resulted in four overarching themes: health system differences,
      navigating the Australian health system, communication barriers and health care
      seeking behaviour. With regard to accessing medicines and pharmacy services, this
      study has shown that there is a gap between resettled refugees' expectations of
      health services and the reality of the Australian health system. Access barriers
      identified included language barriers, issues with the Translating and
      Interpreter Service, a lack of professional communication and cultural beliefs
      affecting health care-seeking behaviour. CONCLUSIONS: This exploratory study has
      established a foundation for further research into the barriers to accessing
      medicines and pharmacy services for resettled refugees. The findings are likely
      to be applicable to a wider population.

PMID- 27896895
TI  - Five-year efficacy and safety of tenofovir-based salvage therapy for patients
      with chronic hepatitis B who previously failed LAM/ADV therapy.
AB  - BACKGROUND: Multidrug-resistant HBV continues to be an important clinical
      problem. The TDF-109 study demonstrated that TDF+/-LAM is an effective salvage
      therapy through 96 weeks for LAM-resistant patients who previously failed ADV add
      on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in
      patients receiving long-term TDF+/-LAM in the TDF-109 study. METHODS: A total of
      59 patients completed the first phase of the TDF-109 study and 54/59 were rolled
      over into a long-term prospective open-label study of TDF+/-LAM 300 mg daily.
      RESULTS: Results are reported at the end of year 5 of treatment. At year 5, 75%
      (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol
      assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained
      HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did
      not meet virological criteria for virological breakthrough (VBT). One patient
      experienced VBT, but this was in the setting of documented non-compliance. The
      response was independent of baseline LAM therapy or mutations conferring ADV
      resistance. Four patients discontinued TDF, one patient was lost to follow-up and
      one died from hepatocellular carcinoma. CONCLUSIONS: Long-term TDF treatment
      appears to be safe and effective in patients with prior failure of LAM and a
      suboptimal response to ADV therapy. These findings confirm that TDF has a high
      genetic barrier to resistance is active against multidrug-resistant HBV, and
      should be the preferred oral anti-HBV agent in CHB patients who fail treatment
      with LAM and ADV.

PMID- 27896896
TI  - Presumed tuberculous uveitis in non-endemic country for tuberculosis: case series
      from a New Zealand tertiary uveitis clinic.
AB  - BACKGROUND: To describe the clinical spectrum of presumed tuberculous (TB)
      uveitis in a developed, non-endemic country of high immigrant population. DESIGN:
      Retrospective review of a consecutive case series. PARTICIPANTS: All 39 patients
      diagnosed with presumed TB uveitis at the tertiary uveitis service in Auckland
      from 2007 to 2014. METHODS: Clinical chart review. MAIN OUTCOME MEASURES: Patient
      demographics, risk factors, ophthalmic manifestations, management and outcome.
      RESULTS: The median age was 37 years (interquartile range [IQR] 31-52) and 56%
      were female. The majority (97%) were born outside of New Zealand, and 77% had no
      TB-related history. Radiological abnormalities consistent with TB were evident in
      seven patients, including three who had culture positive pulmonary disease.
      Anterior uveitis was diagnosed in ten patients (26%), anterior and intermediate
      uveitis in eight (21%), posterior uveitis in 13 (33%) and panuveitis in eight
      (21%). Sixteen (41%) had retinal vasculitis, and five (13%) had multifocal
      serpiginoid choroiditis. Common complications included cataract (51%), ocular
      hypertension (36%), broad posterior synechiae (33%) and cystoid macular oedema
      (28%). Anti-TB treatment was initiated in 30 patients (76%). All but three
      patients completed the intended course of six to 12 months. Following anti-TB
      treatment, 67% remained in remission for at least 12 months, and all but two
      patients successfully stopped systemic steroids. The median initial and final
      visual acuity was 6/9 (IQR 6/6-6/18) and 6/6 (IQR 6/6-6/9), respectively.
      CONCLUSIONS: Despite a wide range of ocular presentations and complications, our
      cohort demonstrated good remission rate and visual prognosis following anti-TB
      treatment in carefully selected patients.

PMID- 27896897
TI  - Expanded clinical use of everolimus eluting bioresorbable vascular scaffolds for
      treatment of coronary artery disease.
AB  - BACKGROUND: Limited data are currently available on the performance of everolimus
      eluting bioresorbable vascular scaffold (BVS) for treatment of complex coronary
      lesions representative of daily practice. METHODS: This is a prospective, mono
      center, single-arm study, reporting data after BVS implantation in patients
      presenting with stable, unstable angina, or non-ST segment elevation myocardial
      infarction caused by de novo stenotic lesions in native coronary arteries. No
      restrictions were applied to lesion complexity. Procedural results and 12-month
      clinical outcomes were reported. RESULTS: A total of 180 patients have been
      evaluated in the present study, with 249 treated coronary lesions. Device Success
      per lesion was 99.2%. A total of 119 calcified lesions were treated. Comparable
      results were observed among severe, moderate and noncalcified lesions in term of
      %diameter stenosis (%DS) (20.3 +/- 10.5%, 17.8 +/- 7.7%, 16.8 +/- 8.6%; P =
      0.112) and acute gain (1.36 +/- 0.41 mm, 1.48 +/- 0.44 mm, 1.56 +/- 0.54 mm; P =
      0.109). In bifurcations (54 lesions), side-branch ballooning after main vessel
      treatment was often performed (33.3%) with low rate of side-branch impairment
      (9.3%). A total of 29 cases with coronary total occlusions were treated. After
      BVS implantation %DS was not different from other lesion types (17.2 +/- 9.4%,
      vs. 17.7 +/- 8.6%; P = 0.780). At one year, all-cause mortality was reported in
      three cases. The rate of target lesion revascularization and target vessel
      revascularization was 3.3%. The rate of definite scaffold thrombosis was 2.6%.
      CONCLUSIONS: The implantation of the everolimus eluting bioresorbable vascular
      scaffold in an expanded range of coronary lesion types and clinical presentations
      was observed to be feasible with promising angiographic results and mid-term
      clinical outcomes. (c) 2016 Wiley Periodicals, Inc.

PMID- 27896898
TI  - Assembling Polyoxo-Titanium Clusters and CdS Nanoparticles to a Porous Matrix for
      Efficient and Tunable H2 -Evolution Activities with Visible Light.
AB  - Polyoxo-titanium clusters (PTCs) are applied to construct highly efficient
      ternary PTC/CdS/MIL-101 visible-light-range H2 -evolution photocatalysts. The
      application of PTCs not only increases the photocatalytic activities but also
      provides a molecular tool to tune them.

PMID- 27896899
TI  - Characterization of a novel form of progressive retinal atrophy in Whippet dogs:
      a clinical, electroretinographic, and breeding study.
AB  - OBJECTIVE: To describe a form of progressive retinal atrophy (PRA) in Whippets
      including clinical, electroretinographic, optical coherence tomographic changes
      and pedigree analysis. ANIMALS STUDIED: Client-owned Whippet dogs (n = 51) living
      in Brazil. PROCEDURES: All animals were submitted for routine ophthalmic
      screening for presumed inherited ocular disease, which included the following:
      visual tests, such as obstacle course tests, in scotopic and photopic conditions,
      cotton ball test, dazzle reflex, ocular fundus evaluation by indirect
      ophthalmoscopy followed by fundus photography. Additionally, electroretinography
      (ERG) and optical coherence tomography (OCT) were performed in 24 and four dogs,
      respectively. RESULTS: Sixteen dogs were diagnosed with PRA. Vision deficits in
      dim light were detected in dogs examined at a young age associated with
      nystagmus. Funduscopic changes included the development of multifocal retinal
      bullae from 6 months of age. Retinal thinning became apparent later, at which
      time the bullae were no longer detected. OCT examination of selected young dogs
      revealed that the retinal bullae were due to separation between photoreceptors
      and the retinal pigment epithelium, and of dogs with more advanced disease
      confirmed the development of retinal thinning. Electroretinography in young dogs
      revealed a negative ERG due to a lack of b-wave in both scotopic and photopic
      recordings. With progression, the ERG became unrecordable. Pedigree analysis
      suggested an autosomal recessive mode of inheritance. CONCLUSION: The retinal
      dystrophy reported here in Whippet dogs has a unique phenotype of an initial lack
      of ERG b-wave, development of retinal bullae then a progressive generalized
      retinal degeneration.

PMID- 27896900
TI  - Molecular features of copper binding proteins involved in copper homeostasis.
AB  - Copper has a wide and important role in biological systems, determining
      conformation and activity of many metalloproteins and enzymes, such as cytochrome
      oxidase and superoxide dismutase . Furthermore, due to its possible reactivity
      with nonspecific proteins and toxic effects, elaborate systems of absorption,
      concentration buffering, delivery to specific protein sites and elimination,
      require a complex system including small carriers, chaperones and active
      transporters. The P-type copper ATPases ATP7A and ATP7B provide an important
      system for acquisition, active transport, distribution and elimination of copper.
      Relevance of copper metabolism to human diseases and therapy is already known. It
      is quite certain that further studies will reveal detailed and useful information
      on biochemical mechanisms and relevance to diseases. (c) 2016 IUBMB Life,
      69(4):211-217, 2017.

PMID- 27896901
TI  - Dynamics of intracellular processes in live-cell systems unveiled by fluorescence
      correlation microscopy.
AB  - Fluorescence fluctuation-based methods are non-invasive microscopy tools
      especially suited for the study of dynamical aspects of biological processes.
      These methods examine spontaneous intensity fluctuations produced by fluorescent
      molecules moving through the small, femtoliter-sized observation volume defined
      in confocal and multiphoton microscopes. The quantitative analysis of the
      intensity trace provides information on the processes producing the fluctuations
      that include diffusion, binding interactions, chemical reactions and
      photophysical phenomena. In this review, we present the basic principles of the
      most widespread fluctuation-based methods, discuss their implementation in
      standard confocal microscopes and briefly revise some examples of their
      applications to address relevant questions in living cells. The ultimate goal of
      these methods in the Cell Biology field is to observe biomolecules as they move,
      interact with targets and perform their biological action in the natural context.
      (c) 2016 IUBMB Life, 69(1):8-15, 2017.

PMID- 27896902
TI  - Substantial reduction in hospital stay of children and adolescents with diabetic
      ketoacidosis after implementation of Clinical Practice Guidelines in a university
      hospital in Saudi Arabia.
AB  - RATIONALE, AIMS AND OBJECTIVES: We aimed to determine the effect of Clinical
      Practice Guideline (CPG) implementation on length of hospital stay of children
      and adolescents with diabetic ketoacidosis (DKA). METHODS: This was a 6-year
      (2008-2014) case-control retrospective study conducted at King Khalid University
      Hospital, Riyadh, that compared patients with DKA managed using CPG with those
      treated before CPG implementation. RESULTS: There were 63 episodes of DKA in 41
      patients managed using CPG compared with 40 episodes in 33 patients treated
      before implementation of CPG. Baseline characteristics of the 2 groups were
      similar (age, sex, newly diagnosed patients, recurrent DKA, DKA severity, and
      mean glycosylated hemoglobin). The mean length of hospital stay (+/-SD) was 68.6
      +/- 53.1 hours after implementation of CPG compared with 107.4 +/- 65.6 hours
      before implementation (P < .001). The reduction in length of hospital stay equals
      to 1700 bed days saved per year per 1000 patients. CONCLUSIONS: Implementation of
      CPG for DKA decreased the length of hospital stay.

PMID- 27896903
TI  - IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING OF A NEURONAL HETEROTOPIA IN THE
      BRAIN OF A CAT.
AB  - A domestic shorthair kitten was presented for evaluation and further treatment of
      seizures. Magnetic resonance imaging of the brain revealed a large multilobulated
      mass in the third ventricle extending into the right lateral ventricle with
      secondary obstructive hydrocephalus. The mass was homogeneously isointense to
      gray matter on T2W, T2-FLAIR, T2* W, T1W, and ADC images, and hyperintense on DW
      EPI. There was no appreciable contrast enhancement. Seizures were managed
      medically and with subsequent ventriculoperitoneal shunt placement. Clinical
      status later deteriorated and the cat was euthanized. Histopathology confirmed
      that the mass was the result of neuronal heterotopia. To the authors' knowledge
      this is the first report of neuronal heterotopia in a cat.

PMID- 27896904
TI  - Contrast-induced encephalopathy following cardiac catheterization.
AB  - OBJECTIVES: To describe the epidemiology, pathophysiology, clinical presentation,
      and management of contrast-induced encephalopathy (CIE) following cardiac
      catheterization. BACKGROUND: CIE is an acute, reversible neurological disturbance
      directly attributable to the intra-arterial administration of iodinated contrast
      medium. METHODS: The PubMed database was searched and all cases in the literature
      were retrieved and reviewed. RESULTS: 52 reports of CIE following cardiac
      catheterization were found. Encephalopathy, motor and sensory disturbances,
      vision disturbance, opthalmoplegia, aphasia, and seizures have been reported.
      Transient cortical blindness is the most commonly reported neurological syndrome,
      occurring in approximately 50% of cases. The putative mechanism involves
      disruption of the blood brain barrier and direct neuronal injury. Contrast
      induced transient vasoconstriction has also been implicated. Symptoms typically
      appear within minutes to hours of contrast administration and resolve entirely
      within 24-48 hr. Risk factors may include hypertension, diabetes mellitus, renal
      impairment, the administration of large volumes of iodinated contrast,
      percutaneous coronary intervention or selective angiography of internal mammary
      grafts, and previous adverse reaction to iodinated contrast. Characteristic
      findings on cerebral imaging include cortical and sub-cortical contrast
      enhancement on computed tomography (CT). Imaging findings in CIE may mimic
      subarachnoid hemorrhage or cerebral ischemia; the Hounsfield scale on CT and the
      apparent diffusion coefficient on magnetic resonance imaging (MRI) are useful
      imaging tools in distinguishing these entities. In some cases, brain imaging is
      normal. Prognosis is excellent with supportive management alone. CIE tends to
      recur, although re-challenge with iodinated contrast without adverse effects has
      been documented. CONCLUSIONS: CIE is an important clinical entity to consider in
      the differential diagnosis of stroke following cardiac catheterization. Given
      that prognosis is excellent with supportive management only, physicians should be
      aware of it, and consider it prior to initiating thrombolysis. (c) 2016 Wiley
      Periodicals, Inc.

PMID- 27896905
TI  - Testing bidirectional associations among emotion regulation strategies and
      substance use: a daily diary study.
AB  - BACKGROUND AND AIMS: Alcohol and marijuana are widely used among college
      students. Emotion regulation strategies have been linked to alcohol and marijuana
      use, but little attention has been devoted to modeling the directionality of
      these associations. The aims of the current study were to test whether (a)
      daytime use of emotion regulation strategies influences the likelihood of evening
      substance use and (b) evening substance use influences the likelihood of next-day
      use of emotion regulation strategies. DESIGN: Longitudinal daily diary data were
      collected for 30 days via on-line surveys. SETTING: Northeastern United States.
      PARTICIPANTS: A total of 1640 college students (mean age = 19.2 years, 54%
      female, 80% European American) were recruited each semester between Spring 2008
      and Spring 2012. MEASUREMENTS: Daily diaries assessed emotion regulation
      strategies (distraction, reappraisal, problem-solving, avoidance) and substance
      use (any drinking, heavy drinking, marijuana use, co-use of any drinking/heavy
      drinking and marijuana). Covariates included gender, age, race/ethnicity,
      fraternity/sorority involvement and baseline depression. FINDINGS: Daytime
      distraction [odds ratio (OR) = 0.95], reappraisal (OR = 0.95) and problem-solving
      (OR = 0.94) predicted lower odds of evening marijuana use (P-values < 0.02).
      Evening heavy drinking (OR = 0.90) and marijuana use (OR = 0.89) predicted lower
      odds of next-day problem-solving, with heavy drinking also predicting higher odds
      (OR = 1.08) of next-day avoidance and marijuana use also predicting higher odds
      (OR = 1.08) of next-day reappraisal (P-values < 0.03). CONCLUSIONS: There appear
      to be reciprocal relations among emotion regulation strategies and substance use:
      greater daytime use of distraction, reappraisal, and problem solving predicts
      lower evening substance use, while higher evening substance use predicts higher
      next-day avoidance and reappraisal but lower next-day problem-solving.

PMID- 27896906
TI  - Identifying patients for safe early hospital discharge following st elevation
      myocardial infarction.
AB  - OBJECTIVES: To examine whether the CADILLAC risk score is an effective method of
      patient stratification for early discharge following ST elevation myocardial
      infarction (STEMI). BACKGROUND: Patients with STEMI are typically hospitalized to
      monitor for serious complications such as arrhythmias, heart failure, and
      reinfarction. Optimal length of stay is unclear. Whether low risk patients can be
      safely discharged before 72 hr of hospitalization is unclear. METHODS: Patients
      with STEMI who underwent successful PCI were retrospectively stratified using
      CADILLAC risk score to low risk (n = 123) and intermediate to high risk (n =
      105). The primary outcome was adverse clinical events at day 3 or later.
      Secondary outcomes were adverse clinical events on day 1 and mortality rates at
      30 days and 31 to 365 days. RESULTS: Low risk patients had lower major adverse
      clinical events at day 3 or later (0 vs. 11.4%, P = 0.0002) and lower total
      mortality at 1 year (0 vs. 4.8%, P = 0.02) than patients with intermediate to
      high risk. Low risk patients were also less likely to have a cardiovascular event
      during the first 24 hr when compared to those with an intermediate to high risk
      score (3.3% vs. 13.3%, P = 0.006). CONCLUSION: Low risk patients identified using
      CADILLAC risk score with STEMI treated successfully with primary PCI have a low
      adverse event rate on the third day or later of hospitalization suggesting that
      an earlier discharge is safe in properly selected patients. Monitoring in a
      noncritical care setting following primary PCI for STEMI may be feasible for
      selected patients. (c) 2016 Wiley Periodicals, Inc.

PMID- 27896907
TI  - Efficacy, acceptability and safety of guided imagery/hypnosis in fibromyalgia - A
      systematic review and meta-analysis of randomized controlled trials.
AB  - : This systematic review aimed at evaluating the efficacy, acceptability and
      safety of guided imagery/hypnosis (GI/H) in fibromyalgia. Cochrane Library,
      MEDLINE, PsycINFO and SCOPUS were screened through February 2016. Randomized
      controlled trials (RCTs) comparing GI/H with controls were analysed. Primary
      outcomes were >=50% pain relief, >=20% improvement of health-related quality of
      life, psychological distress, disability, acceptability and safety at end of
      therapy and 3-month follow-up. Effects were summarized by a random effects model
      using risk differences (RD) or standardized mean differences (SMD) with 95%
      confidence intervals (CI).Seven RCTs with 387 subjects were included into a
      comparison of GI/H versus controls. There was a clinically relevant benefit of
      GI/H compared to controls on >=50% pain relief [RD 0.18 (95% CI 0.02, 0.35)] and
      psychological distress [SMD -0.40 (95% CI -0.70, -0.11)] at the end of therapy.
      Acceptability at the end of treatment for GI/H was not significantly different to
      the control. Two RCTs with 95 subjects were included in the comparison of
      hypnosis combined with cognitive behavioural therapy (CBT) versus CBT alone.
      Combined therapy was superior to CBT alone in reducing psychological distress at
      the end of therapy [SMD -0.50 (95% CI -0.91, -0.09)]. There were no statistically
      significant differences between combined therapy and CBT alone in other primary
      outcomes at the end of treatment and follow-up. No study reported on safety. GI/H
      hold promise in a multicomponent management of fibromyalgia. SIGNIFICANCE: We
      provide a systematic review with meta-analysis on guided imagery and hypnosis for
      fibromyalgia. Current analyses endorse the efficacy and tolerability of guided
      imagery/hypnosis and of the combination of hypnosis with cognitive-behavioural
      therapy in reducing key symptoms of fibromyalgia.

PMID- 27896908
TI  - Bixalomer in Hyperphosphatemic Patients With Chronic Kidney Disease Not on
      Dialysis: Phase 3 Randomized Trial.
AB  - Currently, calcium- or metal-containing phosphate binders are available to treat
      hyperphosphatemia in predialysis patients with chronic kidney disease. Bixalomer,
      a non-calcium, metal-free phosphate binder, has not been studied in these
      patients. We evaluated the efficacy and safety of bixalomer versus placebo for
      treatment of hyperphosphatemia in Japanese predialysis patients with chronic
      kidney disease. This multicenter, randomized, double-blind, phase 3 trial,
      randomized eligible patients 1:1 to receive bixalomer or placebo for 12 weeks.
      Bixalomer was started at 1500 mg/day and adjusted up to 7500 mg/day depending on
      serum phosphorus concentrations. The primary endpoint was change in serum
      phosphorus concentration from baseline to end of treatment. After a 4-week pre
      investigational period, 163 patients (bixalomer: N = 81; placebo: N = 82) were
      randomized. The adjusted mean change (95% confidence interval) from baseline to
      end of treatment in serum phosphorus was significantly greater with bixalomer (
      0.78 [-0.98, -0.57] mg/dL) versus placebo (0.20 [-0.00, 0.41] mg/dL); mean
      difference: -0.98 (-1.27, -0.69), P < 0.001. At end of treatment, 57.5% of
      bixalomer-treated patients achieved target serum phosphorus concentrations, mean
      serum intact parathyroid hormone and fibroblast growth factor-23 decreased, and
      there were no significant changes in corrected serum calcium. The safety and
      tolerability of bixalomer was similar to placebo. The most common drug-related
      adverse events were gastrointestinal (>24% patients per group). There was a
      significant increase in bicarbonate concentrations with bixalomer versus placebo
      (P = 0.003). Bixalomer was superior to placebo for hyperphosphatemia in Japanese
      predialysis patients with chronic kidney disease and may constitute a new
      treatment option.

PMID- 27896909
TI  - Homeless patients' perceptions about using cell phones to manage medications and
      attend appointments.
AB  - OBJECTIVES: The objectives of this study were to (1) describe homeless persons'
      access and use of cell phones and their perceptions about using cell phone alerts
      to help manage medications and attend health care appointments and (2) identify
      demographic characteristics, medication use and appointment history and
      perceptions associated with interest in receiving cell phone alerts to manage
      medications and appointments. METHODS: A cross-sectional survey was conducted in
      2013 at a homeless clinic in Virginia. The questionnaire comprised items about
      cell phone usage, ownership and functions such as text messaging. Participants
      reported medication use and appointment history, perceptions about cell phone
      alerts and interest in receiving alerts to manage medications and appointments.
      Descriptive statistics for all variables are reported. Logistic regression was
      used to examine predictors of interest in using a cell phone to manage
      medications and appointments. KEY FINDINGS: A total of 290 participants completed
      the survey; 89% had a cell phone. Seventy-seven percent were interested in
      appointment reminders, whereas 66%, 60% and 54% were interested in refill
      reminders, medication taking reminders and medication information messages
      respectively. Those who believed reminders were helpful were more likely to be
      interested in medication taking, refill and appointment reminder messages
      compared to those who did not believe reminders were helpful. A history of
      running out of medicine and forgetting appointments were predictors of interest
      in refill and appointment reminders. CONCLUSIONS: Mobile technology is a feasible
      method for communicating medication and appointment information to those
      experiencing or at risk for homelessness.

PMID- 27896910
TI  - Novel delivery technique for atrial septal defect closure in young children
      utilizing the GORE(r) CARDIOFORM(r) septal occluder.
AB  - OBJECTIVES: To develop a novel delivery technique to overcome vascular size
      limitations for device closure of a secundum ASD in the young patient.
      BACKGROUND: The efficacy, clinical utility, and safety of transcatheter closure
      in comparison to surgical closure are well established; however, access vessel
      size remains a potential limitation to device selection in the young patient.
      METHODS: A retrospective medical record review of all cases of secundum ASD
      closure between April 2015 and April 2016 utilizing a novel delivery method
      described herein at two separate academic institutions. The device is
      disassembled allowing the delivery sheath to serve as the introducer. It is
      advanced to the RA with re-introduction of the device allowing for deployment in
      the standard fashion. RESULTS: Overall, 10 patients underwent secundum ASD
      closure via this novel delivery technique. There were six females (60%) and the
      average age at time of the procedure was 4.2 years +/- 1.6 years (range 2-6
      years). The majority of patients had an isolated secundum ASD (70%) with the
      primary indication for closure being right ventricular volume overload (90%). All
      patients had successful placement of a GORE(r) CARDIOFORM(r) Septal Occluder
      (GCSO) with no or trivial residual shunt. No patients had vascular complications
      related to the procedure. CONCLUSIONS: We describe a novel technique for ASD
      closure using the GCSO delivery sheath as the access sheath, which reduces the
      vascular access size requirement by 25%, thus addressing one common limitation
      for percutaneous device closure of a secundum ASD in young patients. (c) 2016
      Wiley Periodicals, Inc.

PMID- 27896911
TI  - The timing and prevalence of intraoperative hypotension in infants undergoing
      laparoscopic pyloromyotomy at a tertiary pediatric hospital.
AB  - BACKGROUND: Intraoperative hypotension may be associated with adverse outcomes in
      children undergoing surgery. Infants and neonates under 6 months of age have less
      autoregulatory cerebral reserve than older infants, yet little information exists
      regarding when and how often intraoperative hypotension occurs in infants. AIMS:
      To better understand the epidemiology of intraoperative hypotension in infants,
      we aimed to determine the prevalence of intraoperative hypotension in a generally
      uniform population of infants undergoing laparoscopic pyloromyotomy. METHODS:
      Vital sign data from electronic records of infants who underwent laparoscopic
      pyloromyotomy with general anesthesia at a children's hospital between January 1,
      1998 and October 4, 2013 were analyzed. Baseline blood pressure (BP) values and
      intraoperative BPs were identified during eight perioperative stages based on
      anesthesia event timestamps. We determined the occurrence of relative (systolic
      BP <20% below baseline) and absolute (mean arterial BP <35 mmHg) intraoperative
      hypotension within each stage. RESULTS: A total of 735 full-term infants and 82
      preterm infants met the study criteria. Relative intraoperative hypotension
      occurred in 77%, 72%, and 58% of infants in the 1-30, 31-60, and 61-90 days age
      groups, respectively. Absolute intraoperative hypotension was seen in 21%, 12%,
      and 4% of infants in the 1-30, 31-60, and 61-90 days age groups, respectively.
      Intraoperative hypotension occurred primarily during surgical prep and throughout
      the surgical procedure. Preterm infants had higher rates of absolute
      intraoperative hypotension than full-term infants. CONCLUSIONS: Relative
      intraoperative hypotension was routine and absolute intraoperative hypotension
      was common in neonates and infants under 91 days of age. Preterm infants and
      infants under 61 days of age experienced the highest rates of absolute and
      relative intraoperative hypotension, particularly during surgical prep and
      throughout surgery.

PMID- 27896912
TI  - Balloon Valvuloplasty to Predict X-ray Projection Angles that are Perpendicular
      to Cardiovascular Structures: A TAVI Patient Feasibility Study.
AB  - OBJECTIVES: The purpose of this work is to describe methods to measure the 3D
      angular orientation of cardiovascular structures based on a planar image of a
      valvuloplasty balloon. These methods facilitate X-ray beam alignment with respect
      to the anatomy of interest. BACKGROUND: X-ray beam projections which are
      perpendicular to the long axis of cardiovascular structures are required to
      support interventional procedures, including transcatheter aortic valve implant
      (TAVI). METHODS: During the TAVI procedure, the 3D angular orientation of the
      LVOT of 10 patients was measured from a single planar image of an aortic
      valvuloplasty balloon and the continuous range of X-ray projection angles which
      are aligned with the aortic valve plane were calculated (research method).
      Misalignment of the X-ray beam and TAVI valve frame was measured from images of
      the deployed valve. The accuracy of the research method was compared to clinical
      standard method to determine appropriate X-ray projection angles, which utilized
      CT and aortography. RESULTS: Using the clinical standard method, the median
      misalignment of the X-ray beam and TAVI valve frame was 8.6 degrees  (range 2.6
      degrees  to 21 degrees ). Misalignment was reduced to 2.5 degrees  (range 0
      degrees  to 10 degrees ) using the research method. CONCLUSIONS: The 3D angular
      orientation of cardiovascular structures can be measured accurately from a single
      X-ray projection image of a known cardiovascular device contained within the
      anatomy of interest. For TAVI procedures, improved X-ray beam alignment may help
      facilitate procedural success. (c) 2016 Wiley Periodicals, Inc.

PMID- 27896914
TI  - An innovative textbook: design and implementation.
AB  - BACKGROUND: The 'flipped classroom' instructional strategy has gained much
      momentum in educational discourse, yet no single educational offering exists in
      postgraduate medical education (PME) to systematically replace the lecture
      element of didactic sessions. This article describes the design and
      implementation of Clinical Anesthesia Fundamentals, the first known textbook in
      PME addressing this gap in resources through the integration of full-length
      interactive multimedia-enhanced video lectures. The 'flipped classroom'
      instructional strategy has gained much momentum in educational discourse
      INNOVATION: The textbook was developed in alignment with the content outline for
      the specialty provided by the American Board of Anesthesiology. Its accompanying
      video lectures, produced at the Media Lab in the Department of Anesthesiology at
      Boston University Medical Center (BUMC), cover the topics in each chapter of the
      textbook and include review questions featuring explanatory feedback. EVALUATION:
      Following a 5-month trial period at the BUMC Anesthesiology Residency Program,
      the complete resident class (25 of 25; 100%) participated in an anonymous,
      Institutional Review Board (IRB) -approved, five-point Likert-type scale survey
      assessing an underlying variable of preference for the use of multimedia learning
      tools. DISCUSSION: Survey results suggest that residents favour technology
      enhanced learning environments in which textbooks are coupled with interactive
      multimedia, and the 'flipped classroom' approach is employed. Although the
      development of digital videos requires time and financial investment, the
      improved accessibility and uniform delivery of didactic content are two positive
      outcomes. CONCLUSION: This textbook provides an example for educators wishing to
      learn how to capitalise on advances in technology to further enhance learning and
      accessibility. Further studies could address the impact of this approach on the
      academic performance of residents.

PMID- 27896913
TI  - Nausea and vomiting in early pregnancy: Effects on food intake and diet quality.
AB  - Experiences of nausea and/or vomiting in pregnancy (NVP) vary greatly, but the
      paucity of studies with pre-pregnancy dietary data mean that little is known
      about the effects of NVP on diet. Using an administered food frequency
      questionnaire, diet was assessed before pregnancy and at 11 and 34 weeks'
      gestation in 2270 participants in a UK birth cohort study (Southampton Women's
      Survey). Experience of NVP in early pregnancy was graded as none, mild, moderate,
      or severe. Participants reported their level of food consumption as more, the
      same, or less than before pregnancy. "Prudent" diet scores (derived using
      principal component analysis) were used to describe participants' diet quality
      before, in early and late pregnancy. In early pregnancy, 89% of women were
      nauseous, although most commonly, the NVP experienced was mild (48%) or moderate
      (30%); 11% had severe NVP. A total of 39% of women reported an increase in their
      level of food intake in early pregnancy; 34% reported a reduction. Increasing
      severity of nausea was associated with changes in intake of a range of foods,
      most notably reduced consumption of vegetables, tea/coffee, rice/pasta, breakfast
      cereals, beans/pulses and citrus fruits/fruit juices and increased consumption of
      white bread, and soft drinks. Increasing severity of nausea was also associated
      with decreasing prudent diet score from before to early pregnancy, such that
      women with severe nausea had prudent diet scores 0.29 SDs lower than those with
      no nausea (P < 0.001). However, this was transient as NVP was not related to
      change in diet quality from before to late pregnancy.

PMID- 27896915
TI  - Evaluation of maternal and perinatal characteristics on childhood lymphoma risk:
      A population-based case-control study.
AB  - BACKGROUND: Lymphoma is one of the most common pediatric malignancies; however,
      there are few well-established risk factors. Therefore, we investigated if
      maternal and perinatal characteristics influenced the risk of childhood lymphoma.
      PROCEDURE: Information on cases (n = 374) diagnosed with lymphoma and born in
      Texas for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth
      certificate controls were randomly selected at a ratio of 10 controls per 1 case
      for the same period of 1995-2011. Unconditional logistic regression was used to
      generate unadjusted (OR) and adjusted odds ratios (aOR) and 95% confidence
      intervals (CI) for the following histologic subtypes: Hodgkin (HL), Burkitt (BL),
      and non-BL non-HLs (non-BL NHLs). RESULTS: Overall, our findings indicate
      specific maternal and perinatal characteristics influence childhood lymphoma
      risk. Mexico-born mothers were more likely to have offspring who developed BL
      compared to mothers born in the United States (U.S.; aOR: 2.15; 95% CI: 1.06
      4.36). Further, mothers who resided at time of delivery in a county on the U.S.
      Mexico border were more likely to give birth to offspring who developed non-BL
      NHL (aOR: 1.72; 95% CI: 1.11-2.67) compared to mothers not living on the U.S.
      Mexico border at time of infant birth. Last, infants born large-for-gestational
      age experienced a twofold increase in BL risk (aOR: 2.00; 95% CI: 1.10-3.65).
      CONCLUSIONS: In this population-based assessment, we confirmed previously
      reported risk predictors of childhood lymphoma, including sex of infant, while
      highlighting novel risk factors that warrant assessment in future studies.

PMID- 27896916
TI  - Dihydroartemisinin counteracts fibrotic portal hypertension via farnesoid X
      receptor-dependent inhibition of hepatic stellate cell contraction.
AB  - Portal hypertension is a frequent pathological symptom occurring especially in
      hepatic fibrosis and cirrhosis. Current paradigms indicate that inhibition of
      hepatic stellate cell (HSC) activation and contraction is anticipated to be an
      attractive therapeutic strategy, because activated HSC dominantly facilitates an
      increase in intrahepatic vein pressure through secreting extracellular matrix and
      contracting. Our previous in vitro study indicated that dihydroartemisinin (DHA)
      inhibited contractility of cultured HSC by activating intracellular farnesoid X
      receptor (FXR). However, the effect of DHA on fibrosis-related portal
      hypertension still requires clarification. In this study, gain- and loss-of
      function models of FXR in HSC were established to investigate the mechanisms
      underlying DHA protection against chronic CCl4 -caused hepatic fibrosis and
      portal hypertension. Immunofluorescence staining visually showed a decrease in
      FXR expression in CCl4 -administrated rat HSC but an increase in that in DHA
      treated rat HSC. Serum diagnostics and morphological analyses consistently
      indicated that DHA exhibited hepatoprotective effects on CCl4 -induced liver
      injury. DHA also reduced CCl4 -caused inflammatory mediator expression and
      inflammatory cell infiltration. These improvements were further enhanced by INT
      747 but weakened by Z-guggulsterone. Noteworthily, DHA, analogous to INT-747,
      significantly lowered portal vein pressure and suppressed fibrogenesis.
      Experiments on mice using FXR shRNA lentivirus consolidated the results above.
      Mechanistically, inhibition of HSC activation and contraction was found as a
      cellular basis for DHA to relieve portal hypertension. These findings
      demonstrated that DHA attenuated portal hypertension in fibrotic rodents possibly
      by targeting HSC contraction via a FXR activation-dependent mechanism. FXR could
      be a target molecule for reducing portal hypertension during hepatic fibrosis.

PMID- 27896918
TI  - Finding the Right Assessment Measures for Young People with Intellectual
      Disabilities Who Display Harmful Sexual Behaviour.
AB  - BACKGROUND: Previous studies and national reports have all noted that a
      significant proportion of the young people who display harmful sexual behaviours
      have intellectual disabilities. However, research on the topic has been scarce.
      This study presents a systematic review of the literature relating to clinical
      instruments specifically developed or adapted for adolescents with intellectual
      disabilities who display harmful sexual behaviours. METHOD: An electronic search
      of databases was completed for published articles in English from the earliest
      possible date to the end of 2013. RESULTS: No published articles met the full
      search criteria. This confirmed the lack of published clinical measures, apart
      from two risk assessment instruments. CONCLUSIONS: Given the lack of measures, it
      is recommended that the focus of future research needs to be on developing or
      adapting instruments that will offer researchers' and clinicians' empirical as
      well as clinical data on this all-too-often-overlooked population of vulnerable
      youth.

PMID- 27896917
TI  - On the pathogenesis of mTOR inhibitor-associated stomatitis (mIAS)-studies using
      an organotypic model of the oral mucosa.
AB  - OBJECTIVE: mTOR inhibitor treatment of solid cancers is associated with mTOR
      inhibitor-associated stomatitis (mIAS) a common, significant, dose-limiting
      toxicity, with aphthous-like lesions. Our objective was to assess the utility of
      a new organotypic model in defining mIAS' pathogenesis. MATERIALS AND METHODS:
      The effect of everolimus on organotypic human oral mucosa was studied. Sterile
      specimens were assessed 24 and 48 h after exposure to varying concentrations of
      everolimus. Morphologic changes and measures of apoptosis, proliferation, and
      levels of six Th1 and Th2 cytokines were studied. RESULTS: Following a 24-h
      incubation, concentrations of 500 ng ml-1 of everolimus resulted in histological
      changes consistent with epithelial injury, disorganization and pre- or early
      apoptosis, increased TUNEL-positive staining (P < 0.05) and reduced PCNA-positive
      staining cells (P < 0.001) and increased levels of IL-6 (P < 0.0001), IL-8 (P <
      0.01), and IFN-gamma (P < 0.09). CONCLUSIONS: Everolimus elicited epithelial
      damage manifest by morphologic changes, increased apoptosis, and decreased
      proliferation with concurrent release of keratinocyte-derived pro-inflammatory
      cytokines in the absence of bacteria. The extent of the effect was concentration
      and time dependent. These results suggest that mIAS is likely initiated by direct
      epithelial injury, independent of the microbiome. Keratinocyte cytokine release
      could likely play a role in accelerating an inflammatory infiltrate.

PMID- 27896920
TI  - Fusion of Ssm6a with a protein scaffold retains selectivity on NaV 1.7 and
      improves its therapeutic potential against chronic pain.
AB  - Voltage-gated sodium channel NaV 1.7 serves as an attractive target for chronic
      pain treatment. Several venom peptides were found to selectively inhibit NaV 1.7
      but with intrinsic problems. Among them, Ssm6a, a recently discovered centipede
      venom peptide, shows the greatest selectivity against NaV 1.7, but dissociates
      from the target too fast and loses bioactivity in synthetic forms. As a disulfide
      rich venom peptide, it is difficult to optimize Ssm6a by artificial mutagenesis
      and produce the peptide with common industrial manufacturing methods. Here, we
      developed a novel protein scaffold fusion strategy to address these concerns.
      Instead of directly mutating Ssm6a, we genetically fused Ssm6a with a protein
      scaffold engineered from human muscle fatty acid-binding protein. The resultant
      fusion protein, SP-TOX, maintained the selectivity and potency of Ssm6a upon NaV
      1.7 but dissociated from target at least 10 times more slowly. SP-TOX
      dramatically reduced inflammatory pain in a rat model through DRG-targeted
      delivery. Importantly, SP-TOX can be expressed cytosolically in Escherichia coli
      and purified in a cost-effective way. In summary, our study provided the first
      example of cytosolically expressed fusion protein with high potency and
      selectivity on NaV 1.7. Our protein scaffold fusion approach may have its broad
      application in optimizing disulfide-rich venom peptides for therapeutic usage.

PMID- 27896919
TI  - Duration of exclusive breastfeeding is a positive predictor of iron status in 6-
      to 10-month-old infants in rural Kenya.
AB  - The prevalence of iron-deficiency anemia (IDA) is high in infants in Sub-Saharan
      Africa. Exclusive breastfeeding of infants to 6 months of age is recommended by
      the World Health Organization, but breast milk is low in iron. Some studies
      suggest exclusive breastfeeding, although beneficial for the infant, may increase
      risk for IDA in resource-limited settings. The objective of this study was to
      determine if duration of exclusive breastfeeding is associated with anemia and
      iron deficiency in rural Kenyan infants. This was a cross-sectional study of 6-10
      month-old infants (n = 134) in southern coastal Kenya. Anthropometrics,
      hemoglobin (Hb), plasma ferritin (PF), soluble transferrin receptor (sTfR), and C
      reactive protein were measured. Body iron stores were calculated from the sTfR/PF
      ratio. Socioeconomic factors, duration of exclusive breastfeeding, nature of
      complementary diet, and demographic characteristics were determined using a
      questionnaire. Mean +/- SD age of the infants was 7.7 +/- 0.8 months. Prevalence
      of anemia, ID, and IDA were 74.6%, 82.1%, and 64.9%, respectively. Months of
      exclusive breastfeeding correlated positively with Hb (r = 0.187; p < .05) and
      negatively with sTfR (r = -0.246; p < .05). sTfR concentrations were lower in
      infants exclusively breastfed at least 6 months compared with those exclusively
      breastfed for less than 6 months (7.6 (6.3, 9) vs. 8.9 (6.7, 13.4); p < .05).
      Controlling for gender, birth weight, and inflammation, months spent exclusively
      breastfeeding was a significant negative predictor of sTfR and a positive
      predictor of Hb (p < .05). The IDA prevalence in rural Kenyan infants is high,
      and greater duration of exclusive breastfeeding predicts better iron status and
      higher Hb in this age group.

PMID- 27896921
TI  - Effect of iron supplementation during lactation on maternal iron status and
      oxidative stress: A randomized controlled trial.
AB  - We examined the effect of iron-containing prenatal vitamin-mineral supplements
      taken postpartum on biomarkers of iron status and oxidative stress. Lactating
      women (n = 114) were randomly assigned to consume daily one iron-free prenatal
      vitamin-mineral supplement plus either 27 mg of iron or placebo for approximately
      3.5 months. The placebo group took the tablets between meals, while those given
      iron took the tablets either with (Fe-W) or between meals (Fe-B). Blood and urine
      samples were collected before and after the supplementation period to analyze
      hemoglobin (Hb), ferritin, hepcidin, transferrin saturation (TfSat), total plasma
      iron, and biomarkers of oxidative stress (isoprostane and 8-hydroxy-2
      deoxyguanosine (8-OHdG)) and inflammation (C-reactive protein (CRP) and alpha-1
      acid glycoprotein (AGP)). There was a trend toward a greater change in Hb among
      women in the Fe-B group compared to placebo (+2.5 vs. -3.7 g/L, respectively, p =
      0.063). When the iron groups were combined, there was a greater change in Hb
      (+1.4 g/L) compared to placebo (p = 0.010). There were trends toward greater
      changes in TfSat (p = 0.087) and total plasma iron (p = 0.065) in the iron groups
      compared to placebo, yet no significant differences between the three groups in
      change in hepcidin (p = 0.291), isoprostane (p = 0.319), or 8-OHdG (p = 0.659),
      nor in change in ferritin among those with elevated CRP at baseline (60% of
      women; p = 0.946); among those without elevated CRP (40% of women), ferritin
      increased more in the iron groups compared to placebo (p = 0.001). Iron
      consumption during lactation moderately increased iron status, particularly among
      women without elevated CRP, and increased Hb, but did not significantly increase
      oxidative stress.

PMID- 27896922
TI  - (-)-Epigallocatechin-3-Gallate Antihyperalgesic Effect Associates With Reduced
      CX3CL1 Chemokine Expression in Spinal Cord.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea with
      beneficial effects on the neuropathic pain alleviation in animal models. Because
      chemokine fractalkine (CX3CL1) has been suggested as an important signal during
      neuropathic pain development, this study aimed to investigate whether CX3CL1
      expression may be modulated by EGCG treatment reducing hyperalgesia in chronic
      constriction injured mice. To this end, Balb/c mice were subjected to a chronic
      constriction injury of sciatic nerve (CCI) and treated with EGCG or vehicle once
      a day during the first week following surgery. Thermal hyperalgesia was tested at
      7 and 14 days post-surgery, and the expression of CX3CL1 and its mRNA were
      analyzed in spinal cord at the end of the experimental period. Results revealed
      that EGCG treatment significantly reduced thermal hyperalgesia in CCI-injured
      mice at short time, and this antihyperalgesic effect was associated with a down
      regulation of CX3CL1 protein expression in the spinal cord. On the other hand,
      EGCG treatment did not affect the CX3CL1 transcription. Overall, our results
      suggest a new role of EGCG-treatment in an experimental model of neuropathic pain
      as a mediator of nociceptive signaling cross talk between neurons and glial cells
      in the dorsal horn of the spinal cord. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 27896924
TI  - Detailed tail proteomic analysis of axolotl (Ambystoma mexicanum) using an mRNA
      seq reference database.
AB  - Salamander axolotl has been emerging as an important model for stem cell research
      due to its powerful regenerative capacity. Several advantages, such as the high
      capability of advanced tissue, organ, and appendages regeneration, promote
      axolotl as an ideal model system to extend our current understanding on the
      mechanisms of regeneration. Acknowledging the common molecular pathways between
      amphibians and mammals, there is a great potential to translate the messages from
      axolotl research to mammalian studies. However, the utilization of axolotl is
      hindered due to the lack of reference databases of genomic, transcriptomic, and
      proteomic data. Here, we introduce the proteome analysis of the axolotl tail
      section searched against an mRNA-seq database. We translated axolotl mRNA
      sequences to protein sequences and annotated these to process the LC-MS/MS data
      and identified 1001 nonredundant proteins. Functional classification of
      identified proteins was performed by gene ontology searches. The presence of some
      of the identified proteins was validated by in situ antibody labeling.
      Furthermore, we have analyzed the proteome expressional changes postamputation at
      three time points to evaluate the underlying mechanisms of the regeneration
      process. Taken together, this work expands the proteomics data of axolotl to
      contribute to its establishment as a fully utilized model.

PMID- 27896923
TI  - Homocysteine modulates 5-lipoxygenase expression level via DNA methylation.
AB  - Elevated levels of homocysteinemia (Hcy), a risk factor for late-onset
      Alzheimer's disease (AD), have been associated with changes in cell methylation.
      Alzheimer's disease is characterized by an upregulation of the 5-lipoxygenase
      (5LO), whose promoter is regulated by methylation. However, whether Hcy activates
      5LO enzymatic pathway by influencing the methylation status of its promoter
      remains unknown. Brains from mice with high Hcy were assessed for the 5LO pathway
      and neuronal cells exposed to Hcy implemented to study the mechanism(s)
      regulating 5LO expression levels and the effect on amyloid beta formation. Diet-
      and genetically induced high Hcy resulted in 5LO protein and mRNA upregulation,
      which was associated with a significant increase of the S-adenosylhomocysteine
      (SAH)/S-adenosylmethionine ratio, and reduced DNA methyltrasferases and
      hypomethylation of 5-lipoxygenase DNA. In vitro studies confirmed these results
      and demonstrated that the mechanism involved in the Hcy-dependent 5LO activation
      and amyloid beta formation is DNA hypomethylation secondary to the elevated
      levels of SAH. Taken together these findings represent the first demonstration
      that Hcy directly influences 5LO expression levels and establish a previously
      unknown cross talk between these two pathways, which is highly relevant for AD
      pathogenesis. The discovery of such a novel link not only provides new
      mechanistic insights in the neurobiology of Hcy, but most importantly new
      therapeutic opportunities for the individuals bearing this risk factor for the
      disease.

PMID- 27896925
TI  - Design, synthesis and in vitro antiplasmodial activity of some bisquinolines
      against chloroquine-resistant strain.
AB  - A series of novel bisquinoline compounds comprising N1 -(7-chloroquinolin-4-yl)
      ethane-1,2-diamine and 7-chloro-N-(2-(piperazin-1-yl)ethyl)quinolin-4-amine
      connected with 7-chloro-4-aminoquinoline containing various amino acids is
      described. We have bio-evaluated the compounds against both chloroquine-sensitive
      (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum in vitro.
      Among the series, compounds 4 and 7 exhibited 1.8- and 10.6-fold superior
      activity as compared to chloroquine (CQ; IC50  = 0.255 +/- 0.049 MUm) against the
      K1 strain with IC50 values 0.137 +/- 0.014 and 0.026 +/- 0.007 MUm, respectively.
      Furthermore, compound 7 also displayed promising activity against the 3D7 strain
      (IC50  = 0.024 +/- 0.003 MUm) of P. falciparum when compared to CQ. All the
      compounds in the series displayed resistance factor between 0.57 and 4.71 as
      against 51 for CQ. These results suggest that bisquinolines can be explored for
      further development as new antimalarial agents active against chloroquine
      resistant P. falciparum.

PMID- 27896926
TI  - (Z)-2-(3-Chlorobenzylidene)-3,4-dihydro-N-(2-methoxyethyl)-3-oxo-2H
      benzo[b][1,4]oxazine-6-carboxamide as GSK-3beta inhibitor: Identification by
      virtual screening and its validation in enzyme- and cell-based assay.
AB  - Glycogen synthase kinase 3beta (GSK-3beta) is a widely investigated molecular
      target for numerous diseases including Alzheimer's disease, cancer, and diabetes
      mellitus. The present study was aimed to discover new scaffolds for GSK-3beta
      inhibition, through protein structure-guided virtual screening approach. With the
      availability of large number of GSK-3beta crystal structures with varying degree
      of RMSD in protein backbone and RMSF in side chain geometry, herein appropriate
      crystal structures were selected based on the characteristic ROC curve and
      percentage enrichment of actives. The validated docking protocol was employed to
      screen a library of 50,000 small molecules using molecular docking and binding
      affinity calculations. Based on the GLIDE docking score, Prime MMGB/SA binding
      affinity, and interaction pattern analysis, the top 50 ligands were selected for
      GSK-3beta inhibition. (Z)-2-(3-chlorobenzylidene)-3,4-dihydro-N-(2-methoxyethyl)
      3-oxo-2H-benzo[b][1,4]oxazine-6-carboxamide (F389-0663, 7) was identified as a
      potent inhibitor of GSK-3beta with an IC50 value of 1.6 MUm. Further, GSK-3beta
      inhibition activity was then investigated in cell-based assay. The treatment of
      neuroblastoma N2a cells with 12.5 MUm of F389-0663 resulted in the significant
      increase in GSK-3beta Ser9 levels, which is indicative of the GSK-3beta
      inhibitory activity of a compound. The molecular dynamic simulations were carried
      out to understand the interactions of F389-0663 with GSK-3beta protein.

PMID- 27896927
TI  - A retrospective review of anesthesia and perioperative care in children with
      medium-chain acyl-CoA dehydrogenase deficiency.
AB  - BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency is the most common
      genetically determined disorder of mitochondrial fatty acid oxidation.
      Decompensation can result in hypoglycemia, seizures, coma, and death but may be
      prevented by ensuring glycogen stores do not become depleted. Perioperative care
      is of interest as surgery, fasting, and infection may all trigger decompensation
      and the safety of anesthetic agents has been questioned. Current guidelines from
      the British Inherited Metabolic Disease Group advise on administering fluid
      containing 10% glucose during the perioperative period. AIM: To review the
      management of anesthesia and perioperative care for children with medium-chain
      acyl-CoA dehydrogenase deficiency and determine the frequency and nature of any
      complications. METHOD: A retrospective review of case notes of children with
      medium-chain acyl-CoA dehydrogenase deficiency undergoing anesthesia between 1997
      and 2014. RESULTS: Fourteen patients underwent 21 episodes of anesthesia. In 20
      episodes, the patient received a glucose-containing fluid during their
      perioperative fast, of which eight received fluid containing 10% dextrose
      throughout the entire perioperative period. No episodes of hypoglycemia or
      decompensation occurred, but perioperative hyperglycemia occurred in five
      episodes. A propofol bolus was administered at induction in 16 episodes and
      volatile agents were administered for maintenance of anesthesia in all episodes
      without any observed complications. In one episode, delayed offset of atracurium
      was reported. CONCLUSIONS: Perioperative metabolic decompensation and
      hypoglycemia appear to be uncommon in children who are well and receive glucose
      supplementation. Hyperglycemia may occur as a consequence of surgery and glucose
      supplementation. Propofol boluses and volatile anesthetic agents were used
      without any apparent complications. Prolonged action of atracurium was reported
      in one case, suggesting that nondepolarizing muscle relaxants may have delayed
      offset in this patient group. We do not recommend any particular approach to
      anesthesia but would advise administering glucose supplementation according to
      current guidelines, frequent monitoring of blood glucose perioperatively, and
      monitoring of neuromuscular blockade.

PMID- 27896928
TI  - Liddle syndrome: clinical and genetic profiles.
AB  - Liddle syndrome is a rare autosomal dominant monogenic form of hypertension. The
      authors analyzed clinical and genetic features of 12 cases of Liddle syndrome,
      the largest sample size ever reported. Clinical data were studied
      retrospectively. The exon 13 of the beta and gamma subunits of the epithelial
      sodium channel were amplified and sequenced in the peripheral blood leukocytes of
      the patients. The onset age of the 12 patients was 15.5+/-3.3 years. Their blood
      pressures were poorly controlled, and serum potassium levels in most patients
      were <3.0 mmol/L. Upright plasma renin activity and plasma aldosterone
      concentration were suppressed in all patients. All patients were treated with
      triamterene, and blood pressures were well controlled and serum potassium levels
      returned to normal. The serum creatinine level rose to 124 and 161 MUmol/L,
      respectively, in two patients upon triamterene treatment, and returned to normal
      soon after treatment was discontinued. Eight mutation alleles were identified,
      and three mutations were newly identified.

PMID- 27896930
TI  - You are not alone.

PMID- 27896929
TI  - Impact of inflammation and oxidative stress on carotid intima-media thickness in
      obstructive sleep apnea patients without metabolic syndrome.
AB  - Obstructive sleep apnea (OSA) increases the risk of cardiovascular diseases, and
      carotid intima-media thickness (IMT) is a good indicator of the severity of
      atherosclerotic disease. This study tested the hypothesis that inflammation and
      oxidative stress determined carotid IMT in patients with OSA. The carotid IMT,
      mean systolic and diastolic pressure (night and morning) were significantly
      higher and the level of thiols and high-density lipoprotein were significantly
      lower in our 121 OSA patients than in 27 controls (P < 0.05). The apnea/hypopnea
      index was correlated positively with E-selectin (r = 0.222, P = 0.014), total
      cholesterol (r = 0.185, P = 0.042), low-density lipoprotein (r = 0.264, P =
      0.003) and HbA1c levels (r = 0.304, P = 0.001), but inversely with high-density
      lipoprotein level (r = -0.203, P = 0.025) in the 121 patients with OSA. In OSA
      subjects, multiple linear regression analysis revealed that age, systolic blood
      pressure and intercellular cell adhesion molecule-1 level associated
      independently with carotid IMT. Besides both age and systolic blood pressure, our
      study demonstrated that intercellular cell adhesion molecule-1 level was
      associated significantly with carotid IMT in those patients who had OSA but
      without metabolic syndrome.

PMID- 27896931
TI  - Risk of empyema in patients with chronic liver disease and cirrhosis: A
      nationwide, population-based cohort study.
AB  - BACKGROUND: Empyema is an important complication for patients with chronic liver
      disease and cirrhosis (CLDC). However, no study has investigated this
      relationship by using a population-based cohort study. METHODS: We used the
      National Health Insurance Research Data of Taiwan to identify a cohort of 76 027
      CLDC patients newly diagnosed in 2000-2010 and a comparison cohort without CLDC
      of same size matched by age, gender and the year of diagnosis. The occurrence of
      empyema was monitored until the end of 2011. The hazard ratios (HRs) of empyema
      were estimated using the Cox model. RESULTS: The overall incidence of empyema was
      66% greater in the CLDC group than in the non-CLDC group (3.85 vs 2.32/10 000
      person-years, P<.001), with an adjusted HR of 1.54 (95% confidence interval
      [CI]=1.24-1.90). Compared with those without CLDC, adjusted HRs of empyema were
      4.96 (95% CI=3.40-7.24) for patients with cirrhosis and 4.75 (95% CI=3.11-7.24)
      for patients with alcoholic CLDC. Further analyses revealed significant adjusted
      HRs of empyema among CLDC patients with ascites (5.76, 95% CI=4.13-8.04) and with
      gastrointestinal haemorrhage (1.60, 95% CI=1.03-2.48), compared to those without
      the respective disorders. Analyses using propensity score matched CLDC and non
      CLDC cohorts revealed similar results. CONCLUSION: The present study shows that
      CLDC patients have an increased risk of empyema. These patients need timely
      monitor for the risk of empyema, particularly for those with comorbid cirrhosis,
      alcoholic disorder, gastrointestinal haemorrhage and ascites.

PMID- 27896932
TI  - Mesoionic insecticides: a novel class of insecticides that modulate nicotinic
      acetylcholine receptors.
AB  - BACKGROUND: As the world population grows towards 9 billion by 2050, it is
      projected that food production will need to increase by 60%. A critical part of
      this growth includes the safe and effective use of insecticides to reduce the
      estimated 20-49% loss of global crop yields owing to pests. The development of
      new insecticides will help to sustain this protection and overcome insecticide
      resistance. RESULTS: A novel class of mesoionic compounds has been discovered,
      with exceptional insecticidal activity on a range of Hemiptera and Lepidoptera.
      These compounds bind to the orthosteric site of the nicotinic acetylcholine
      receptor and result in a highly potent inhibitory action at the receptor with
      minimal agonism. The synthesis, biological activity, optimization and mode of
      action will be discussed. CONCLUSION: Triflumezopyrim insect control will provide
      a powerful tool for control of hopper species in rice throughout Asia.
      Dicloromezotiaz can provide a useful control tool for lepidopteran pests, with an
      underexploited mode of action among these pests. (c) 2016 Society of Chemical
      Industry.

PMID- 27896933
TI  - Feasibility and clinical integration of molecular profiling for target
      identification in pediatric solid tumors.
AB  - BACKGROUND: The role of tumor molecular profiling in directing targeted therapy
      utilization remains to be defined for pediatric tumors. We aimed to evaluate the
      feasibility of a sequencing and molecular biology tumor board (MBB) program, and
      its clinical impact on children with solid tumors. PROCEDURE: We report on a
      single-center MBB experience of 60 pediatric patients with a poor prognosis or
      relapsed/refractory solid tumors screened between October 2014 and November 2015.
      Tumor molecular profiling was performed with panel-based next-generation
      sequencing and array comparative genomic hybridization. RESULTS: Mean age was 12
      +/- 5.7 years (range 0.1-21.5); main tumor types were high-grade gliomas (n =
      14), rare sarcomas (n = 9), and neuroblastomas (n = 8). The indication was a poor
      prognosis tumor at diagnosis for 16 patients and relapsed (n = 26) or refractory
      disease (n = 18) for the remaining 44 patients. Molecular profiling was feasible
      in 58 patients. Twenty-three patients (40%) had a potentially actionable finding.
      Patients with high-grade gliomas had the highest number of targetable alterations
      (57%). Six of the 23 patients subsequently received a matched targeted therapy
      for a period ranging from 16 days to 11 months. The main reasons for not
      receiving targeted therapy were poor general condition (n = 5), pursuit of
      conventional therapy (n = 6), or lack of pediatric trial (n = 4). CONCLUSIONS:
      Pediatric molecular profiling is feasible, with more than a third of patients
      being eligible to receive targeted therapy, yet only a small proportion were
      treated with these therapies. Analysis at diagnosis may be useful for children
      with very poor prognosis tumsors.

PMID- 27896935
TI  - Sandcastle Worm-Inspired Blood-Resistant Bone Graft Binder Using a Sticky Mussel
      Protein for Augmented In Vivo Bone Regeneration.
AB  - Xenogenic bone substitutes are commonly used during orthopedic reconstructive
      procedures to assist bone regeneration. However, huge amounts of blood
      accompanied with massive bone loss usually increase the difficulty of placing the
      xenograft into the bony defect. Additionally, the lack of an organic matrix leads
      to a decrease in the mechanical strength of the bone-grafted site. For effective
      bone grafting, this study aims at developing a mussel adhesion-employed bone
      graft binder with great blood-resistance and enhanced mechanical properties. The
      distinguishing water (or blood) resistance of the binder originates from
      sandcastle worm-inspired complex coacervation using negatively charged hyaluronic
      acid (HA) and a positively charged recombinant mussel adhesive protein (rMAP)
      containing tyrosine residues. The rMAP/HA coacervate stabilizes the agglomerated
      bone graft in the presence of blood. Moreover, the rMAP/HA composite binder
      enhances the mechanical and hemostatic properties of the bone graft agglomerate.
      These outstanding features improve the osteoconductivity of the agglomerate and
      subsequently promote in vivo bone regeneration. Thus, the blood-resistant
      coacervated mussel protein glue is a promising binding material for effective
      bone grafting and can be successfully expanded to general bone tissue
      engineering.

PMID- 27896934
TI  - Increased identification of novel variants in type 2 diabetes, birth weight and
      their pleiotropic loci.
AB  - BACKGROUND: Clinical and epidemiological findings point to an association between
      type 2 diabetes (T2D) and low birth weight. However, the nature of the
      relationship is largely unknown. The aim of this study was to identify novel
      single nucleotide polymorphisms (SNPs) in T2D and birth weight, and their
      pleiotropic loci. METHODS: A pleiotropy-informed conditional false discovery rate
      (cFDR) method was applied to two independent genome-wide association studies
      (GWAS) summary statistics of T2D (n = 149 821) and birth weight (n = 26 836).
      RESULTS: A conditional Q-Q plot showed strong enrichment of genetic variants in
      T2D conditioned on different levels of association with birth weight. 133 T2D
      associated SNPs, including 120 novel SNPs, were identified with a significance
      threshold of cFDR < 0.05; 13 significant birth weight-associated SNPs, including
      12 novel SNPs (cFDR < 0.05) were identified. Conjunctional cFDR (ccFDR) analysis
      identified nine pleiotropic loci, including seven novel loci, shared by both T2D
      and birth weight (ccFDR < 0.05). Two novel SNPs located at the CDK5 regulatory
      subunit-associated protein 1-like 1 (CDKAL1; rs1012635; cFDR < 0.05) and
      adenylate cyclase 5 (ADCY5; rs4677887; cFDR < 0.05) genes are of note. These two
      genes increase the risk of T2D and low birth weight through the pathway of the
      "fetal insulin hypothesis." CONCLUSION: Several pleiotropic loci were identified
      between T2D and birth weight by leveraging GWAS results. The results make it
      possible to explain a greater proportion of trait heritability and improve our
      understanding of the shared pathophysiology between T2D and birth weight.

PMID- 27896936
TI  - Health-related quality of life and adherence to hydroxyurea in adolescents and
      young adults with sickle cell disease.
AB  - BACKGROUND: Complications related to sickle cell disease (SCD) result in
      significant declines in health-related quality of life (HRQOL). While hydroxyurea
      reduces SCD complications, adherence remains suboptimal. The study's objectives
      were to assess the feasibility of Internet-based electronic assessment of HRQOL
      in SCD clinic and to examine the relationship between HRQOL and hydroxyurea
      adherence in adolescents and young adults (AYAs) with SCD. PROCEDURE: A cross
      sectional survey was administered on tablets to 34 AYAs (12-22 years old) in a
      SCD clinic from January through December 2015. Study measures included Patient
      Reported Outcomes Measurement Information System (PROMIS(r) ) computerized
      adaptive testing and (c)Modified Morisky Adherence Scale 8-items ((c)MMAS-8).
      RESULTS: Participants (59% male, 91% Black) had median age of 13.5 (range 12-18)
      years. Ninety-one percent completed PROMIS(r) measures electronically in the
      clinic, meeting our feasibility criterion of >=85% completion rate. (c)MMAS-8
      scores positively correlated with fetal hemoglobin (HbF) (rs = 0.34, P = 0.04)
      and mean corpuscular volume (MCV) (rs = 0.42, P = 0.01) and inversely correlated
      with fatigue (rs = -0.45, P = 0.01), depression (rs = -0.3, P = 0.08), and social
      isolation (rs = -0.78, P = 0.02). Low (c)MMAS-8 scores, indicating poor
      adherence, were associated with worse fatigue (P = 0.001) and trended toward
      significance for pain (P = 0.07) and depression (P = 0.06). Homozygous hemoglobin
      S disease patients with low HbF (<16%) had worse social isolation (P = 0.04) and
      those with low MCV (<102 fl) reported worse fatigue (P = 0.001), pain (P = 0.01),
      mobility (P = 0.01), and social isolation (P = 0.04). CONCLUSIONS: HRQOL
      assessment in the SCD clinic is feasible. SCD patients with low hydroxyurea
      adherence and/or low HbF or MCV levels had worse HRQOL scores, particularly
      fatigue. Future prospective studies examining the relationship between HRQOL and
      hydroxyurea adherence are warranted.

PMID- 27896937
TI  - Effect of tailored dietary guidance for pregnant women on nutritional status: A
      double-cohort study.
AB  - This double cohort study aimed to evaluate the effect of tailored dietary
      guidance for pregnant women on dietary intake, nutritional status, and infant
      birth weight. Healthy pregnant women were recruited at an antenatal clinic during
      two phases over 2 years. The historical controls were analyzed a year prior to
      the intervention group. In both groups, data were collected at 19-26 gestational
      weeks (baseline) and at 34-37 gestational weeks (outcome measurement). The
      intervention included the following: (a) assessments of maternal dietary
      nutritional intake using the brief self-administered diet history questionnaire,
      (b) individual feedback based on the assessments of maternal nutritional status,
      (c) tailored guidance for a healthy diet, (d) original cooking recipes, and (e)
      goal sharing. Mann-Whitney U test was used to compare the outcome data between
      the groups. Of the 378 eligible women, 309 women had follow-up questionnaire
      data. Blood samples were obtained from 202 women. Despite a lack of improvement
      in reported dietary intake, plasma eicosapentaenoic acid (p = .002),
      docosahexaenoic acid (p < .001), arachidonic acid (p < .001), and dihomo-gamma
      linolenic acid (p < .001) concentrations as well as maternal weight gain (p =
      .019) were significantly higher in the intervention group. However, serum folate
      (p = .031) concentration was significantly lower in the intervention group, and
      there were no significant differences between the groups in 25-hydroxy vitamin D
      levels, blood count, average birth weight, and rate of low birth weight infants.
      Assessment-based tailored guidance individualized to maternal dietary intake
      might partially contribute to improved nutrition in pregnant women.

PMID- 27896939
TI  - A multimodal study of impulsivity and body weight: Integrating behavioral,
      cognitive, and neuroimaging approaches.
AB  - OBJECTIVE: Dimensions of impulsivity are related to obesity. Accordingly,
      characterization of impulsivity in individuals with overweight and obesity holds
      promise for more targeted and effective intervention. METHODS: Forty-five
      individuals (13 males, mean age = 32.6, mean body mass index [BMI] = 30.7) were
      recruited to determine the role of impulsivity in elevated body weight by
      evaluating: (1) trait impulsivity via impulsive sensation-seeking scale (ImpSS),
      (2) state impulsivity via continuous performance test, and (3) activation and
      integration of brain cognitive control regions via functional magnetic resonance
      imaging during a response inhibition task (i.e., stop signal task). RESULTS:
      Positive correlations were found between BMI and trait (ImpSS) as well as state
      impulsivity (continuous performance test, beta). BMI was negatively correlated
      with regional activation in the temporal lobe and insula during successful
      response inhibition. Further, there was a positive association between BMI and
      functional connectivity between the right inferior frontal gyrus and right middle
      frontal gyrus during successful response inhibition. Mediation analyses revealed
      that ImpSS mediated the relationship between BMI and neural response in the right
      inferior frontal gyrus. CONCLUSIONS: This multimodal study provides concordant
      evidence for behavioral, cognitive, and neural markers of impulsivity and
      elevated BMI, highlighting the need to address inhibitory control mechanisms for
      more effective weight management programs.

PMID- 27896938
TI  - Population Pharmacokinetic/Pharmacodynamic Modeling of Tumor Size Dynamics in
      Pembrolizumab-Treated Advanced Melanoma.
AB  - Pembrolizumab is a potent immune-modulating antibody active in advanced melanoma,
      as demonstrated in the KEYNOTE-001, -002, and -006 studies. Longitudinal tumor
      size modeling was pursued to quantify exposure-response relationships for
      efficacy. A mixture model was first developed based on an initial dataset from
      KEYNOTE-001 to describe four patterns of tumor growth and shrinkage. For
      subsequent analyses, tumor size measurements were adequately described by a
      single consolidated model structure that captured continuous tumor size with a
      combination of growth and regression terms, as well as a fraction of tumor
      responsive to therapy. This revised model structure provided a framework to
      efficiently evaluate the impact of covariates and pembrolizumab exposure. Both
      models indicated that exposure to the drug was not a significant predictor of
      tumor size response, demonstrating that the dose range evaluated (2 and 10 mg/kg
      every 3 weeks) is likely near or at the plateau of maximal response.

PMID- 27896940
TI  - Empowering women to breastfeed: Does the Baby Friendly Initiative make a
      difference?
AB  - The Baby-Friendly Hospital Initiative (BFI) is currently presented worldwide as
      the gold standard model of care for promoting and supporting breastfeeding.
      However, there is a lack of understanding about the ways in which health
      services, including the BFI, address the cultural change from a disembodied
      practice (formula feeding) to an embodied one (breastfeeding) in contexts where
      formula feeding is the norm. We used a qualitative case study methodology to
      compare the embodied experience of breastfeeding and the maternal experience of
      breastfeeding promotion and support services between mothers receiving care from
      institutions with low and high levels of BFI implementation in Quebec, Canada. A
      total of 11 focus groups were conducted with mothers from six institutions-three
      with high and three with low levels of BFI implementation. We found the flexible
      approach to breastfeeding duration, characteristic of BFI services in our study,
      helped to avoid maternal guilt and shame; the shift to focusing on potential
      barriers and strategies for overcoming them empowered women to negotiate changes
      in infant feeding with others and self by addressing the embodied experience of a
      practice that may not feel natural at the beginning. Findings have implications
      for the concept of habitus and the construction of the breastfeeding body; we
      suggest that habitus can change if agents are provided with discursive tools to
      negotiate this embodied change. Implications for BFI services include the need to
      implement the 10 steps in a flexible, family-centred way that focuses on
      empowering women rather than simply reaching outcomes.

PMID- 27896941
TI  - Patient-reported neuropathic pain in adolescent and young adult cancer patients.
AB  - BACKGROUND: Neuropathic pain, a known complication of cancer and its treatments,
      negatively impacts quality of life. There are limited data using screening tools
      to aid in the diagnosis of neuropathic pain in cancer patients. Our primary
      objective was to determine the proportion of adolescent and young adult cancer
      patients reporting neuropathic pain on a patient-completed, neuropathic pain
      screening tool. PROCEDURES: This prospective, cohort study enrolled patients 14
      39 years of age who were receiving therapy for primary cancer diagnosis, cancer
      relapse, or had recently completed treatment. The painDETECT, a patient
      completed, neuropathic pain screening tool used down to age 14, was administered
      a maximum of three times in on-therapy patients and once in off-therapy patients.
      Provider documentation of neuropathic pain at the corresponding visit was
      abstracted from the medical record. RESULTS: Seventy-eight patients participated.
      Median (interquartile range) age at study enrollment was 18.1 (16-19.4) years and
      47% were female. Cancer diagnoses included 41% leukemia, 26% solid tumor, 23%
      lymphoma, and 10% central nervous system tumor. The proportion of patients
      reporting neuropathic pain was 26% (95% confidence interval [CI] 16-40%) in on
      therapy patients and 11% (95% CI 3-27%) in off-therapy patients. In patients
      reporting neuropathic pain, only 26% had a clinical diagnosis of neuropathic pain
      documented in the medical record at the corresponding visit. CONCLUSIONS:
      Neuropathic pain occurs in one in four adolescents and young adults receiving
      cancer therapy. Use of screening tools may increase the detection of neuropathic
      pain in adolescents and young adults receiving cancer therapy and could
      ultimately improve pain treatment.

PMID- 27896942
TI  - Mid-childhood outcomes of infant siblings at familial high-risk of autism
      spectrum disorder.
AB  - Almost 20% of infants with an older sibling with autism spectrum disorder (ASD)
      exhibit ASD themselves by age 3 years. The longer-term outcomes of high-risk
      infants are less clear. We examined symptoms of ASD, attention
      deficit/hyperactivity disorder (ADHD) and anxiety, language, IQ, and adaptive
      behaviour at age 7 years in high- and low-risk children prospectively studied
      since the first year of life. Clinical outcomes were compared between high-risk
      children who met diagnostic criteria for ASD at age 7 (HR-ASD-7 group, n = 15),
      high-risk children without ASD (HR-Non-ASD-7 group, n = 24), and low-risk control
      children (LR group, n = 37). Diagnostic stability between age 3 and 7 years was
      moderate, with five children who did not meet diagnostic criteria for ASD at age
      3 years being assigned the diagnosis at age 7, and three children showing the
      opposite pattern. The HR-ASD-7 group showed elevated ADHD and anxiety symptoms
      and had lower adaptive behaviour scores than LR controls. The HR-Non-ASD-7 group
      had higher repetitive behaviour, lower adaptive functioning and elevated scores
      on one anxiety subscale (Separation Anxiety) compared to LR controls, but
      evidence for subclinical ASD symptoms (the broader autism phenotype, BAP) was
      limited in the group as a whole, although we identified a subgroup with elevated
      ASD traits. The difficulties experienced by high-risk siblings at school-age
      extend beyond ASD symptoms. The pattern of difficulties exhibited by the HR-ASD-7
      group may inform our understanding of developmental trajectories of co-occurring
      psychopathology in ASD. Autism Res 2017, 10: 546-557. (c) 2016 International
      Society for Autism Research, Wiley Periodicals, Inc.

PMID- 27896943
TI  - Angiotensin-(1-7) protects cardiomyocytes against high glucose-induced injuries
      through inhibiting reactive oxygen species-activated leptin-p38 mitogen-activated
      protein kinase/extracellular signal-regulated protein kinase 1/2 pathways, but
      not the leptin-c-Jun N-terminal kinase pathway in vitro.
AB  - AIMS/INTRODUCTION: Angiotensin-(1-7) (Ang-[1-7]), recognized as a new bioactive
      peptide in the renin-angiotensin system, shows biological and pharmacological
      properties in diabetic cardiovascular diseases. The leptin-induced p38 mitogen
      activated protein kinase (MAPK) pathway has been reported to contribute to high
      glucose (HG)-induced injury. In the present study, we showed the mechanism of how
      Ang-(1-7) can protect against HG-stimulated injuries in H9c2 cells. MATERIALS AND
      METHODS: H9c2 cells were treated with 35 mmol/L glucose (HG) for 24 h to
      establish a model of HG-induced damage. Apoptotic cells were observed by Hoechst
      33258 staining. Cell viability was analyzed by cell counter kit-8. The expression
      of protein was detected by western blot. Reactive oxygen species was tested by
      2',7'-dichlorodihydrofluorescein diacetate staining. Mitochondrial membrane
      potential was measured by 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl
      imidacarbocyanine iodide staining. RESULTS: The present results showed that
      treating H9c2 cells with HG obviously enhanced the expressions of both the leptin
      and phosphorylated (p)-MAPK pathway. However, the overexpression levels of leptin
      and p-p38 MAPK/p-extracellular signal-regulated protein kinase 1/2 (ERK1/2), but
      not p-c-Jun N-terminal kinase, were significantly suppressed by treatment of the
      cells with Ang-(1-7). Additionally, leptin antagonist also markedly suppressed
      the overexpressions of p38 and ERK1/2 induced by HG, whereas leptin antagonist
      had no influence on the overexpression of c-Jun N-terminal kinase. More
      remarkable, Ang-(1-7), leptin antagonist, SB203580 or SP600125, respectively,
      significantly inhibited the injuries induced by HG, such as the increased cell
      viability, decreased apoptotic rate, reduction of ROS production and increased
      mitochondrial membrane potential. Furthermore, the overexpressions of p38 MAPK,
      ERK1/2 and leptin were suppressed by N-actyl-L-cystine. CONCLUSIONS: The present
      findings show that Ang-(1-7) protects from HG-stimulated damage as an inhibitor
      of the reactive oxygen species-leptin-p38 MAPK/ERK1/2 pathways, but not the
      leptin-c-Jun N-terminal kinase pathway in vitro.

PMID- 27896944
TI  - Quantifying bias in survival estimates resulting from loss to follow-up among
      children with lymphoma in Malawi.
AB  - Pediatric lymphoma is common in sub-Saharan Africa, where survival estimates are
      often based on limited follow-up with incomplete retention, introducing potential
      for bias. We compared follow-up and overall survival (OS) between passive and
      active tracing within a prospective cohort of children with lymphoma in Malawi.
      Median follow-up times were 4.4 months (interquartile range [IQR] 2.0-9.4) and
      10.8 months (IQR 6.2-20.6) in passive and active follow-up, respectively. Twelve
      month overall survival (OS) was 69% (95% confidence interval [CI] 54-80) in
      passive and 44% (95% CI 34-54) in active follow-up. Passive follow-up
      significantly overestimated the OS and underestimated the mortality. Efforts to
      improve retention in regional studies are needed.

PMID- 27896945
TI  - A Fundamental Tandem Mass Spectrometry Study of the Collision-Activated
      Dissociation of Small Deprotonated Molecules Related to Lignin.
AB  - The collision-activated fragmentation pathways and reaction mechanisms of 34
      deprotonated model compounds representative of lignin degradation products were
      explored experimentally and computationally. The compounds were evaporated and
      ionized by using negative-ion mode electrospray ionization doped with NaOH to
      produce abundant deprotonated molecules. The ions were isolated and subjected to
      collision-activated dissociation (CAD). Their fragment ions were then isolated
      and also subjected to CAD. This was repeated until no further fragmentation was
      observed (up to MS6 ). This approach enabled the identification of characteristic
      reaction pathways and delineation of reasonable fragmentation mechanisms for
      deprotonated molecules containing various functional groups. The varying
      fragmentation patterns observed for different types of compounds allow for the
      identification of the functionalities in these compounds. This information was
      utilized to identify the presence of specific functionalities and their
      combinations in molecules in an organosolv lignin sample.

PMID- 27896946
TI  - Dynamic laser speckle angiography achieved by eigen-decomposition filtering.
AB  - A new approach is proposed for statistically analysis of laser speckle signals
      emerged from a living biological tissue based on eigen-decomposition to separate
      the dynamic speckle signals due to moving blood cells from the static speckle
      signals due to static tissue components, upon which to achieve angiography of the
      interrogated tissue in vivo. The proposed approach is tested by imaging mouse ear
      pinna in vivo, demonstrating its capability of providing detailed microvascular
      networks with high contrast, and high temporal and spatial resolutions. It is
      expected to provide further opportunities for laser speckle imaging in the
      biomedical and clinical applications where microvascular response to certain
      stimulus or tissue injury is of interest.

PMID- 27896948
TI  - Acute partial sleep deprivation due to environmental noise increases weight gain
      by reducing energy expenditure in rodents.
AB  - OBJECTIVE: Chronic partial sleep deprivation (SD) by environmental noise exposure
      increases weight gain and feeding in rodents, which contrasts weight loss after
      acute SD by physical methods. This study tested whether acute environmental noise
      exposure reduced sleep and its effect on weight gain, food intake, physical
      activity, and energy expenditure (EE). It was hypothesized that acute exposure
      would (1) increase weight gain and feeding and (2) reduce sleep, physical
      activity, and EE (total and individual components); and (3) behavioral changes
      would persist throughout recovery from SD. METHODS: Three-month old male Sprague
      Dawley rats slept ad libitum, were noise exposed (12-h light cycle), and allowed
      to recover (36 h). Weight gain, food intake, sleep/wake, physical activity, and
      EE were measured. RESULTS: Acute environmental noise exposure had no effect on
      feeding, increased weight gain (P < 0.01), and reduced sleep (P < 0.02), physical
      activity (P < 0.03), total EE (P < 0.05), and several components (P < 0.05).
      Reductions in EE and physical activity persisted during recovery. CONCLUSIONS:
      Reductions in EE during sleep, rest, and physical activity reduce total EE and
      contribute to weight gain during acute SD and recovery from SD. These data
      emphasize the importance of increasing physical activity after SD to prevent
      obesity.

PMID- 27896947
TI  - Reduced modulation of thalamocortical connectivity during exposure to sensory
      stimuli in ASD.
AB  - Recent evidence for abnormal thalamic connectivity in autism spectrum disorders
      (ASD) and sensory processing disorders suggests the thalamus may play a role in
      sensory over-responsivity (SOR), an extreme negative response to sensory stimuli,
      which is common in ASD. However, there is yet little understanding of changes in
      thalamic connectivity during exposure to aversive sensory inputs in individuals
      with ASD. In particular, the pulvinar nucleus of the thalamus is implicated in
      atypical sensory processing given its role in selective attention, regulation,
      and sensory integration. This study aimed to examine the role of pulvinar
      connectivity in ASD during mildly aversive sensory input. Functional magnetic
      resonance imaging was used to examine connectivity with the pulvinar during
      exposure to mildly aversive auditory and tactile stimuli in 38 youth (age 9-17;
      19 ASD, 19 IQ-matched typically developing (TD)). Parents rated children's SOR
      severity on two standard scales. Compared to TD, ASD participants displayed
      aberrant modulation of connectivity between pulvinar and cortex (including
      sensory-motor and prefrontal regions) during sensory stimulation. In ASD
      participants, pulvinar-amygdala connectivity was correlated with severity of SOR
      symptoms. Deficits in modulation of thalamocortical connectivity in youth with
      ASD may reflect reduced thalamo-cortical inhibition in response to sensory
      stimulation, which could lead to difficulty filtering out and/or integrating
      sensory information. An increase in amygdala connectivity with the pulvinar might
      be partially responsible for deficits in selective attention as the amygdala
      signals the brain to attend to distracting sensory stimuli. Autism Res 2017, 10:
      801-809. (c) 2016 International Society for Autism Research, Wiley Periodicals,
      Inc.

PMID- 27896949
TI  - Sarcopenia predicts readmission and mortality in elderly patients in acute care
      wards: a prospective study.
AB  - BACKGROUND: The aim of this study is to assess the prevalence of sarcopenia and
      investigate the associations between sarcopenia and long-term mortality and
      readmission in a population of elderly inpatients in acute care wards. METHODS:
      We conducted a prospective observational study in the acute care wards of a
      teaching hospital in western China. The muscle mass was estimated according to a
      previously validated anthropometric equation. Handgrip strength was measured with
      a handheld dynamometer, and physical performance was measured via a 4 m walking
      test. Sarcopenia was defined according to the recommended diagnostic algorithm of
      the Asia Working Group for Sarcopenia. The survival status and readmission
      information were obtained via telephone interviews at 12, 24, and 36 months
      during the 3 year follow-up period following the baseline investigation. RESULTS:
      Two hundred and eighty-eight participants (mean age: 81.1 +/- 6.6 years) were
      included. Forty-nine participants (17.0%) were identified as having sarcopenia.
      This condition was similar in men and women (16.9% vs. 17.5%, respectively, P =
      0.915). During the 3 year follow-up period, 49 men (22.7%) and 9 women (16.4%)
      died (P = 0.307). The mortality of sarcopenic participants was significantly
      increased compared with non-sarcopenic participants (40.8% vs. 17.1%,
      respectively, P < 0.001). After adjusting for age, sex and other confounders,
      sarcopenia was an independent predictor of 3 year mortality (adjusted hazard
      ratio: 2.49; 95% confidential interval: 1.25-4.95) and readmission (adjusted
      hazard ratio: 1.81; 95% confidential interval: 1.17-2.80). CONCLUSIONS:
      Sarcopenia, which is evaluated by a combination of anthropometric measures, gait
      speed, and handgrip strength, is valuable to predict hospital readmission and
      long-term mortality in elderly patients in acute care wards.

PMID- 27896951
TI  - Hydrogen peroxide modulates energy metabolism and oxidative stress in cultures of
      permanent human Muller cells MIO-M1.
AB  - In this study the influence of hydrogen peroxide (H2 O2 ) on the redox state,
      NADH protein binding, and mitochondrial membrane potential in Muller cells is
      investigated. Cultures of permanent human Muller cells MIO-M1 were exposed to H2
      O2 in 75 uM and 150 uM concentration for two hours. Fluorescence emission spectra
      and lifetimes were measured by two-photon microscopy (excitation wavelength: 740
      nm) at the mitochondria which were identified in the microscopic images by their
      fluorescence properties (spectra and intensity). Two hours of H2 O2 exposure did
      not impair viability of MIO-M1 cells in culture. Whereas the ratio of flavine- to
      NADH fluorescence intensity did not change under either H2 O2 concentration, the
      mean lifetime was significantly different between controls, not exposed to H2 O2
      , and the 150 uM H2 O2 exposure (972 +/- 63 ps vs. 1152 +/- 64 ps, p = 0.014).
      One hour after cessation of the H2 O2 exposure, the value retuned to that of the
      control (983 +/- 36 ps). A hyperpolarization of the mitochondrial membrane under
      150 uM H2 O2 was found. These findings suggest a shift form free to protein-bound
      NADH in mitochondria as well as a hyperpolarization of their inner membrane which
      could be related to an impairment of Muller cell function despite their preserved
      viability. Exposure of human Muller cells to hydrogen peroxide for two hours
      results in a reversible change of protein binding of mitochondrial NADH upon
      unchanged redox ratio. The mitochondrial membrane potential is increased during
      exposure.

PMID- 27896950
TI  - PPARgamma agonists negatively regulate alphaIIbbeta3 integrin outside-in
      signaling and platelet function through up-regulation of protein kinase A
      activity.
AB  - : Essentials peroxisome proliferator-activated receptor gamma (PPARgamma)
      agonists inhibit platelet function. PPARgamma agonists negatively regulate
      outside-in signaling via integrin alphaIIbbeta3. PPARgamma agonists disrupt the
      interaction of Galpha13 with integrin beta3. This is attributed to an
      upregulation of protein kinase A activity. SUMMARY: Background Agonists for the
      peroxisome proliferator-activated receptor (PPARgamma) have been shown to have
      inhibitory effects on platelet activity following stimulation by GPVI and GPCR
      agonists. Objectives Profound effects on thrombus formation led us to suspect a
      role for PPARgamma agonists in the regulation of integrin alphaIIbbeta3 mediated
      signaling. Both GPVI and GPCR signaling pathways lead to alphaIIbbeta3
      activation, and signaling through alphaIIbbeta3 plays a critical role in platelet
      function and normal hemostasis. Methods The effects of PPARgamma agonists on the
      regulation of alphaIIbbeta3 outside-in signaling was determined by monitoring the
      ability of platelets to adhere and spread on fibrinogen and undergo clot
      retraction. Effects on signaling components downstream of alphaIIbbeta3
      activation were also determined following adhesion to fibrinogen by Western
      blotting. Results Treatment of platelets with PPARgamma agonists inhibited
      platelet adhesion and spreading on fibrinogen and diminished clot retraction. A
      reduction in phosphorylation of several components of alphaIIbbeta3 signaling,
      including the integrin beta3 subunit, Syk, PLCgamma2, focal adhesion kinase (FAK)
      and Akt, was also observed as a result of reduced interaction of the integrin
      beta3 subunit with Galpha13. Studies of VASP phosphorylation revealed that this
      was because of an increase in PKA activity following treatment with PPARgamma
      receptor agonists. Conclusions This study provides further evidence for
      antiplatelet actions of PPARgamma agonists, identifies a negative regulatory role
      for PPARgamma agonists in the control of integrin alphaIIbbeta3 outside-in
      signaling, and provides a molecular basis by which the PPARgamma agonists
      negatively regulate platelet activation and thrombus formation.

PMID- 27896953
TI  - Highly Selective Upgrading of Biomass-Derived Alcohol Mixtures for Jet/Diesel
      Fuel Components.
AB  - In light of the increasing concern about the energy and environmental problems
      caused by the combustion of petroleum-based fuels (e.g., jet and diesel fuels),
      the development of new procedures for their sustainable production from renewable
      biomass-derived platform compounds has attracted tremendous attention recently.
      Long-chain ketones/alcohols are promising fuel components owing to the fuel
      properties that closely resemble those of traditional fuels. The focus of this
      report is the production of long-chain ketones/alcohols by direct upgrading of
      biomass-derived short-chain alcohol mixtures (e.g., isopropanol-butanol-ethanol
      mixtures) in pure water. An efficient Pd catalyst system was developed for these
      highly selective transformations. Long-chain ketones/alcohols (C8 -C19 ), which
      can be used as precursors for renewable jet/diesel fuel, were obtained in good-to
      high selectivity (>90 %) by using the developed Pd catalyst.

PMID- 27896956
TI  - COMPUTATIONAL APPROACHES TO UNDERSTANDING THE EVOLUTION OF MOLECULAR FUNCTION.
AB  - The following sections are included:IntroductionOverview of
      ContributionsReferences.

PMID- 27896955
TI  - Adsorption and Reactive Desorption on Metal-Organic Frameworks: A Direct Strategy
      for Lactic Acid Recovery.
AB  - Biomass-derived lactic acid (LA) is an important platform chemical towards the
      sustainable production of numerous materials. However, the fermentation process
      currently in use is limited by the difficult recovery of the LA product from the
      fermentation broth and results in the generation of stoichiometric amounts of
      gypsum waste. Herein, we show that metal-organic frameworks (MOFs) of the UiO
      66(Zr) type are effective adsorbents for the separation of LA from aqueous
      (buffer) solutions. These frameworks based on zirconium clusters and terephthalic
      acid derivatives display a tremendous uptake (up to 42 wt %) and a high affinity
      for LA. The latter can further be tuned by changing the hydrogen-bonding
      properties of the functional groups present on the organic ligand. A Rietveld
      refinement disclosed the specific interaction of LA with the clusters of UiO
      66(Zr) and a preferential adsorption on open zirconium sites. Taking advantage of
      the catalytic activity of UiO-66(Zr), desorption of LA was performed in alcohols
      to recover up to 73 % as ester. Applied to the recovery of LA, adsorption and
      reactive desorption offer a direct and gypsum-free strategy as an alternative for
      the current multi-step process.

PMID- 27896952
TI  - Muscle strength in breast cancer patients receiving different treatment regimes.
AB  - BACKGROUND: Muscle dysfunction and sarcopenia have been associated with poor
      performance status, an increased mortality risk, and greater side effects in
      oncologic patients. However, little is known about how performance is affected by
      cancer therapy. We investigated muscle strength in breast cancer patients in
      different adjuvant treatment settings and also compared it with data from healthy
      individuals. METHODS: Breast cancer patients (N = 255) from two randomized
      controlled exercise trials, staged 0-III and aged 54.4 +/- 9.4 years, were
      categorized into four groups according to their treatment status. In a cross
      sectional design, muscle function was assessed bilaterally by isokinetic
      dynamometry (0 degrees , 60 degrees , 180 degrees /s) as maximal voluntary
      isometric contraction (MVIC) and maximal isokinetic peak torque (MIPT) in
      shoulder rotators and knee flexors and extensors. Additionally, muscular fatigue
      index (FI%) and shoulder flexibility were evaluated. Healthy women (N = 26), aged
      53.3 +/- 9.8 years, were tested using the same method. Analysis of covariance was
      used to estimate the impact of different cancer treatments on skeletal muscle
      function with adjustment for various clinical and socio-demographic factors.
      RESULTS: Consistently, lower muscle strength was measured in shoulder and knee
      strength in patients after chemotherapy. On average, patients had up to 25% lower
      strength in lower extremities and 12-16% in upper extremities in MVIC and MIPT
      during cancer treatment compared with healthy women. No substantial difference
      between patient groups in shoulder strength, but significantly lower shoulder
      flexibility in patients with radical mastectomy was measured. Chemotherapy
      treated patients had consistently higher FI%. No serious adverse events were
      reported. CONCLUSIONS: Breast cancer patients showed markedly impaired muscle
      strength and joint dysfunctions before and after anticancer treatment. The
      significant differences between patients and healthy individuals underline the
      need of exercise therapy as early as possible in order to prevent or counteract
      the loss of muscle function after curative surgery as well as the consequences of
      neo-/adjuvant chemotherapy.

PMID- 27896957
TI  - IDENTIFICATION AND ANALYSIS OF BACTERIAL GENOMIC METABOLIC SIGNATURES.
AB  - With continued rapid growth in the number and quality of fully sequenced and
      accurately annotated bacterial genomes, we have unprecedented opportunities to
      understand metabolic diversity. We selected 101 diverse and representative
      completely sequenced bacteria and implemented a manual curation effort to
      identify 846 unique metabolic variants present in these bacteria. The presence or
      absence of these variants act as a metabolic signature for each of the bacteria,
      which can then be used to understand similarities and differences between and
      across bacterial groups. We propose a novel and robust method of summarizing
      metabolic diversity using metabolic signatures and use this method to generate a
      metabolic tree, clustering metabolically similar organisms. Resulting analysis of
      the metabolic tree confirms strong associations with well-established biological
      results along with direct insight into particular metabolic variants which are
      most predictive of metabolic diversity. The positive results of this manual
      curation effort and novel method development suggest that future work is needed
      to further expand the set of bacteria to which this approach is applied and use
      the resulting tree to test broad questions about metabolic diversity and
      complexity across the bacterial tree of life.

PMID- 27896954
TI  - Effect of carbohydrate counting using bolus calculators on glycemic control in
      type 1 diabetes patients during continuous subcutaneous insulin infusion.
AB  - The present study examined the long-term efficacy of insulin pump therapy for
      type 1 diabetes patients when carried out using carbohydrate counting with bolus
      calculators for 1 year. A total of 22 type 1 diabetes patients who had just
      started continuous subcutaneous insulin infusion were examined and divided into
      two groups: one that was educated about carbohydrate counting using bolus
      calculators (n = 14); and another that did not use bolus calculators (n = 8).
      After 1 year, the hemoglobin A1c levels of the patient group that used bolus
      calculators decreased persistently and significantly (P = 0.0297), whereas those
      of the other group did not. The bodyweight, total daily dose of insulin and bolus
      percentage of both groups did not change. Carbohydrate counting using bolus
      calculators is necessary to achieve optimal and persistent glycemic control in
      patients undergoing continuous subcutaneous insulin infusion.

PMID- 27896958
TI  - WHEN SHOULD WE NOT TRANSFER FUNCTIONAL ANNOTATION BETWEEN SEQUENCE PARALOGS?
AB  - Current automated computational methods to assign functional labels to unstudied
      genes often involve transferring annotation from orthologous or paralogous genes,
      however such genes can evolve divergent functions, making such transfer
      inappropriate. We consider the problem of determining when it is correct to make
      such an assignment between paralogs. We construct a benchmark dataset of two
      types of similar paralogous pairs of genes in the well-studied model organism S.
      cerevisiae: one set of pairs where single deletion mutants have very similar
      phenotypes (implying similar functions), and another set of pairs where single
      deletion mutants have very divergent phenotypes (implying different functions).
      State of the art methods for this problem will determine the evolutionary history
      of the paralogs with references to multiple related species. Here, we ask a first
      and simpler question: we explore to what extent any computational method with
      access only to data from a single species can solve this problem.We consider
      divergence data (at both the amino acid and nucleotide levels), and network data
      (based on the yeast protein-protein interaction network, as captured in BioGRID),
      and ask if we can extract features from these data that can distinguish between
      these sets of paralogous gene pairs. We find that the best features come from
      measures of sequence divergence, however, simple network measures based on degree
      or centrality or shortest path or diffusion state distance (DSD), or shared
      neighborhood in the yeast protein-protein interaction (PPI) network also contain
      some signal. One should, in general, not transfer function if sequence divergence
      is too high. Further improvements in classification will need to come from more
      computationally expensive but much more powerful evolutionary methods that
      incorporate ancestral states and measure evolutionary divergence over multiple
      species based on evolutionary trees.

PMID- 27896959
TI  - PROSNET: INTEGRATING HOMOLOGY WITH MOLECULAR NETWORKS FOR PROTEIN FUNCTION
      PREDICTION.
AB  - Automated annotation of protein function has become a critical task in the post
      genomic era. Network-based approaches and homology-based approaches have been
      widely used and recently tested in large-scale community-wide assessment
      experiments. It is natural to integrate network data with homology information to
      further improve the predictive performance. However, integrating these two
      heterogeneous, high-dimensional and noisy datasets is non-trivial. In this work,
      we introduce a novel protein function prediction algorithm ProSNet. An integrated
      heterogeneous network is first built to include molecular networks of multiple
      species and link together homologous proteins across multiple species. Based on
      this integrated network, a dimensionality reduction algorithm is introduced to
      obtain compact low-dimensional vectors to encode proteins in the network.
      Finally, we develop machine learning classification algorithms that take the
      vectors as input and make predictions by transferring annotations both within
      each species and across different species. Extensive experiments on five major
      species demonstrate that our integration of homology with molecular networks
      substantially improves the predictive performance over existing approaches.

PMID- 27896960
TI  - ON THE POWER AND LIMITS OF SEQUENCE SIMILARITY BASED CLUSTERING OF PROTEINS INTO
      FAMILIES.
AB  - Over the last decades, we have observed an ongoing tremendous growth of available
      sequencing data fueled by the advancements in wet-lab technology. The sequencing
      information is only the beginning of the actual understanding of how organisms
      survive and prosper. It is, for instance, equally important to also unravel the
      proteomic repertoire of an organism. A classical computational approach for
      detecting protein families is a sequence-based similarity calculation coupled
      with a subsequent cluster analysis. In this work we have intensively analyzed
      various clustering tools on a large scale. We used the data to investigate the
      behavior of the tools' parameters underlining the diversity of the protein
      families. Furthermore, we trained regression models for predicting the expected
      performance of a clustering tool for an unknown data set and aimed to also
      suggest optimal parameters in an automated fashion. Our analysis demonstrates the
      benefits and limitations of the clustering of proteins with low sequence
      similarity indicating that each protein family requires its own distinct set of
      tools and parameters. All results, a tool prediction service, and additional
      supporting material is also available online under
      http://proteinclustering.compbio.sdu.dk.

PMID- 27896961
TI  - IMAGING GENOMICS.
AB  - Imaging genomics is an emerging research field, where integrative analysis of
      imaging and omics data is performed to provide new insights into the phenotypic
      characteristics and genetic mechanisms of normal and/or disordered biological
      structures and functions, and to impact the development of new diagnostic,
      therapeutic and preventive approaches. The Imaging Genomics Session at PSB 2017
      aims to encourage discussion on fundamental concepts, new methods and innovative
      applications in this young and rapidly evolving field.

PMID- 27896962
TI  - ADAPTIVE TESTING OF SNP-BRAIN FUNCTIONAL CONNECTIVITY ASSOCIATION VIA A MODULAR
      NETWORK ANALYSIS.
AB  - Due to its high dimensionality and high noise levels, analysis of a large brain
      functional network may not be powerful and easy to interpret; instead,
      decomposition of a large network into smaller subcomponents called modules may be
      more promising as suggested by some empirical evidence. For example, alteration
      of brain modularity is observed in patients suffering from various types of brain
      malfunctions. Although several methods exist for estimating brain functional
      networks, such as the sample correlation matrix or graphical lasso for a sparse
      precision matrix, it is still difficult to extract modules from such network
      estimates. Motivated by these considerations, we adapt a weighted gene co
      expression network analysis (WGCNA) framework to resting-state fMRI (rs-fMRI)
      data to identify modular structures in brain functional networks. Modular
      structures are identified by using topological overlap matrix (TOM) elements in
      hierarchical clustering. We propose applying a new adaptive test built on the
      proportional odds model (POM) that can be applied to a high-dimensional setting,
      where the number of variables (p) can exceed the sample size (n) in addition to
      the usual p < n setting. We applied our proposed methods to the ADNI data to test
      for associations between a genetic variant and either the whole brain functional
      network or its various subcomponents using various connectivity measures. We
      uncovered several modules based on the control cohort, and some of them were
      marginally associated with the APOE4 variant and several other SNPs; however, due
      to the small sample size of the ADNI data, larger studies are needed.

PMID- 27896963
TI  - EXPLORING BRAIN TRANSCRIPTOMIC PATTERNS: A TOPOLOGICAL ANALYSIS USING SPATIAL
      EXPRESSION NETWORKS.
AB  - Characterizing the transcriptome architecture of the human brain is fundamental
      in gaining an understanding of brain function and disease. A number of recent
      studies have investigated patterns of brain gene expression obtained from an
      extensive anatomical coverage across the entire human brain using experimental
      data generated by the Allen Human Brain Atlas (AHBA) project. In this paper, we
      propose a new representation of a gene's transcription activity that explicitly
      captures the pattern of spatial co-expression across different anatomical brain
      regions. For each gene, we define a Spatial Expression Network (SEN), a network
      quantifying co-expression patterns amongst several anatomical locations. Network
      similarity measures are then employed to quantify the topological resemblance
      between pairs of SENs and identify naturally occurring clusters. Using network
      theoretical measures, three large clusters have been detected featuring distinct
      topological properties. We then evaluate whether topological diversity of the
      SENs reects significant differences in biological function through a gene
      ontology analysis. We report on evidence suggesting that one of the three SEN
      clusters consists of genes specifically involved in the nervous system, including
      genes related to brain disorders, while the remaining two clusters are
      representative of immunity, transcription and translation. These findings are
      consistent with previous studies showing that brain gene clusters are generally
      associated with one of these three major biological processes.

PMID- 27896964
TI  - INTEGRATIVE ANALYSIS FOR LUNG ADENOCARCINOMA PREDICTS MORPHOLOGICAL FEATURES
      ASSOCIATED WITH GENETIC VARIATIONS.
AB  - Lung cancer is one of the most deadly cancers and lung adenocarcinoma (LUAD) is
      the most common histological type of lung cancer. However, LUAD is highly
      heterogeneous due to genetic difference as well as phenotypic differences such as
      cellular and tissue morphology. In this paper, we systematically examine the
      relationships between histological features and gene transcription. Specifically,
      we calculated 283 morphological features from histology images for 201 LUAD
      patients from TCGA project and identified the morphological feature with strong
      correlation with patient outcome. We then modeled the morphology feature using
      multiple co-expressed gene clusters using Lasso-regression. Many of the gene
      clusters are highly associated with genetic variations, specifically DNA copy
      number variations, implying that genetic variations play important roles in the
      development cancer morphology. As far as we know, our finding is the first to
      directly link the genetic variations and functional genomics to LUAD histology.
      These observations will lead to new insight on lung cancer development and
      potential new integrative biomarkers for prediction patient prognosis and
      response to treatments.

PMID- 27896966
TI  - ENFORCING CO-EXPRESSION IN MULTIMODAL REGRESSION FRAMEWORK.
AB  - We consider the problem of multimodal data integration for the study of complex
      neurological diseases (e.g. schizophrenia). Among the challenges arising in such
      situation, estimating the link between genetic and neurological variability
      within a population sample has been a promising direction. A wide variety of
      statistical models arose from such applications. For example, Lasso regression
      and its multitask extension are often used to fit a multivariate linear
      relationship between given phenotype(s) and associated observations. Other
      approaches, such as canonical correlation analysis (CCA), are widely used to
      extract relationships between sets of variables from different modalities. In
      this paper, we propose an exploratory multivariate method combining these two
      methods. More Specifically, we rely on a 'CCA-type' formulation in order to
      regularize the classical multimodal Lasso regression problem. The underlying
      motivation is to extract discriminative variables that display are also co
      expressed across modalities. We first evaluate the method on a simulated dataset,
      and further validate it using Single Nucleotide Polymorphisms (SNP) and
      functional Magnetic Resonance Imaging (fMRI) data for the study of schizophrenia.

PMID- 27896965
TI  - IDENTIFICATION OF DISCRIMINATIVE IMAGING PROTEOMICS ASSOCIATIONS IN ALZHEIMER'S
      DISEASE VIA A NOVEL SPARSE CORRELATION MODEL.
AB  - Brain imaging and protein expression, from both cerebrospinal fluid and blood
      plasma, have been found to provide complementary information in predicting the
      clinical outcomes of Alzheimer's disease (AD). But the underlying associations
      that contribute to such a complementary relationship have not been previously
      studied yet. In this work, we will perform an imaging proteomics association
      analysis to explore how they are related with each other. While traditional
      association models, such as Sparse Canonical Correlation Analysis (SCCA), can not
      guarantee the selection of only disease-relevant biomarkers and associations, we
      propose a novel discriminative SCCA (denoted as DSCCA) model with new penalty
      terms to account for the disease status information. Given brain imaging,
      proteomic and diagnostic data, the proposed model can perform a joint association
      and multi-class discrimination analysis, such that we can not only identify
      disease-relevant multimodal biomarkers, but also reveal strong associations
      between them. Based on a real imaging proteomic data set, the empirical results
      show that DSCCA and traditional SCCA have comparable association performances.
      But in a further classification analysis, canonical variables of imaging and
      proteomic data obtained in DSCCA demonstrate much more discrimination power
      toward multiple pairs of diagnosis groups than those obtained in SCCA.

PMID- 27896967
TI  - METHODS TO ENSURE THE REPRODUCIBILITY OF BIOMEDICAL RESEARCH.
AB  - Science is not done in a vacuum - across fields of biomedicine, scientists have
      built on previous research and used data published in previous papers. A mainstay
      of scientific inquiry is the publication of one's research and recognition for
      this work is given in the form of citations and notoriety - ideally given in
      proportion to the quality of the work. Academic incentives, however, may
      encourage individual researchers to prioritize career ambitions over scientific
      truth. Recently, the New England Journal of Medicine published a commentary
      calling scientists who repurpose data "research parasites" who misuse data
      generated by others to demonstrate alternative hypotheses. In our opinion, the
      concept of data hoarding not only runs contrary to the spirit of, but also
      hinders scientific progress. Scientific research is meant to seek objective
      truth, rather than promote a personal agenda, and the only way to do so is
      through maximum transparency and reproducibility, no matter who is using the
      data....

PMID- 27896968
TI  - EXPLORING THE REPRODUCIBILITY OF PROBABILISTIC CAUSAL MOLECULAR NETWORK MODELS.
AB  - Network reconstruction algorithms are increasingly being employed in biomedical
      and life sciences research to integrate large-scale, high-dimensional data
      informing on living systems. One particular class of probabilistic causal
      networks being applied to model the complexity and causal structure of biological
      data is Bayesian networks (BNs). BNs provide an elegant mathematical framework
      for not only inferring causal relationships among many different molecular and
      higher order phenotypes, but also for incorporating highly diverse priors that
      provide an efficient path for incorporating existing knowledge. While significant
      methodological developments have broadly enabled the application of BNs to
      generate and validate meaningful biological hypotheses, the reproducibility of
      BNs in this context has not been systematically explored. In this study, we aim
      to determine the criteria for generating reproducible BNs in the context of
      transcription-based regulatory networks. We utilize two unique tissues from
      independent datasets, whole blood from the GTEx Consortium and liver from the
      Stockholm-Tartu Atherosclerosis Reverse Network Engineering Team (STARNET) study.
      We evaluated the reproducibility of the BNs by creating networks on data
      subsampled at different levels from each cohort and comparing these networks to
      the BNs constructed using the complete data. To help validate our results, we
      used simulated networks at varying sample sizes. Our study indicates that
      reproducibility of BNs in biological research is an issue worthy of further
      consideration, especially in light of the many publications that now employ
      findings from such constructs without appropriate attention paid to
      reproducibility. We find that while edge-to-edge reproducibility is strongly
      dependent on sample size, identification of more highly connected key driver
      nodes in BNs can be carried out with high confidence across a range of sample
      sizes.

PMID- 27896969
TI  - REPRODUCIBLE DRUG REPURPOSING: WHEN SIMILARITY DOES NOT SUFFICE.
AB  - Repurposing existing drugs for new uses has attracted considerable attention over
      the past years. To identify potential candidates that could be repositioned for a
      new indication, many studies make use of chemical, target, and side effect
      similarity between drugs to train classifiers. Despite promising prediction
      accuracies of these supervised computational models, their use in practice, such
      as for rare diseases, is hindered by the assumption that there are already known
      and similar drugs for a given condition of interest. In this study, using
      publicly available data sets, we question the prediction accuracies of supervised
      approaches based on drug similarity when the drugs in the training and the test
      set are completely disjoint. We first build a Python platform to generate
      reproducible similarity-based drug repurposing models. Next, we show that, while
      a simple chemical, target, and side effect similarity based machine learning
      method can achieve good performance on the benchmark data set, the prediction
      performance drops sharply when the drugs in the folds of the cross validation are
      not overlapping and the similarity information within the training and test sets
      are used independently. These intriguing results suggest revisiting the
      assumptions underlying the validation scenarios of similarity-based methods and
      underline the need for unsupervised approaches to identify novel drug uses inside
      the unexplored pharmacological space. We make the digital notebook containing the
      Python code to replicate our analysis that involves the drug repurposing platform
      based on machine learning models and the proposed disjoint cross fold generation
      method freely available at github.com/emreg00/repurpose.

PMID- 27896970
TI  - EMPOWERING MULTI-COHORT GENE EXPRESSION ANALYSIS TO INCREASE REPRODUCIBILITY.
AB  - A major contributor to the scientific reproducibility crisis has been that the
      results from homogeneous, single-center studies do not generalize to
      heterogeneous, real world populations. Multi-cohort gene expression analysis has
      helped to increase reproducibility by aggregating data from diverse populations
      into a single analysis. To make the multi-cohort analysis process more feasible,
      we have assembled an analysis pipeline which implements rigorously studied meta
      analysis best practices. We have compiled and made publicly available the results
      of our own multi-cohort gene expression analysis of 103 diseases, spanning 615
      studies and 36,915 samples, through a novel and interactive web application. As a
      result, we have made both the process of and the results from multi-cohort gene
      expression analysis more approachable for non-technical users.

PMID- 27896971
TI  - RABIX: AN OPEN-SOURCE WORKFLOW EXECUTOR SUPPORTING RECOMPUTABILITY AND
      INTEROPERABILITY OF WORKFLOW DESCRIPTIONS.
AB  - As biomedical data has become increasingly easy to generate in large quantities,
      the methods used to analyze it have proliferated rapidly. Reproducible and
      reusable methods are required to learn from large volumes of data reliably. To
      address this issue, numerous groups have developed workflow specifications or
      execution engines, which provide a framework with which to perform a sequence of
      analyses. One such specification is the Common Workflow Language, an emerging
      standard which provides a robust and flexible framework for describing data
      analysis tools and workflows. In addition, reproducibility can be furthered by
      executors or workflow engines which interpret the specification and enable
      additional features, such as error logging, file organization, optim1izations to
      computation and job scheduling, and allow for easy computing on large volumes of
      data. To this end, we have developed the Rabix Executor, an open-source workflow
      engine for the purposes of improving reproducibility through reusability and
      interoperability of workflow descriptions.

PMID- 27896972
TI  - DATA SHARING AND REPRODUCIBLE CLINICAL GENETIC TESTING: SUCCESSES AND CHALLENGES.
AB  - Open sharing of clinical genetic data promises to both monitor and eventually
      improve the reproducibility of variant interpretation among clinical testing
      laboratories. A significant public data resource has been developed by the NIH
      ClinVar initiative, which includes submissions from hundreds of laboratories and
      clinics worldwide. We analyzed a subset of ClinVar data focused on specific
      clinical areas and we find high reproducibility (>90% concordance) among labs,
      although challenges for the community are clearly identified in this dataset. We
      further review results for the commonly tested BRCA1 and BRCA2 genes, which show
      even higher concordance, although the significant fragmentation of data into
      different silos presents an ongoing challenge now being addressed by the BRCA
      Exchange. We encourage all laboratories and clinics to contribute to these
      important resources.

PMID- 27896973
TI  - PATTERNS IN BIOMEDICAL DATA-HOW DO WE FIND THEM?
AB  - Given the exponential growth of biomedical data, researchers are faced with
      numerous challenges in extracting and interpreting information from these large,
      high-dimensional, incomplete, and often noisy data. To facilitate addressing this
      growing concern, the "Patterns in Biomedical Data-How do we find them?" session
      of the 2017 Pacific Symposium on Biocomputing (PSB) is devoted to exploring
      pattern recognition using data-driven approaches for biomedical and precision
      medicine applications. The papers selected for this session focus on novel
      machine learning techniques as well as applications of established methods to
      heterogeneous data. We also feature manuscripts aimed at addressing the current
      challenges associated with the analysis of biomedical data.

PMID- 27896974
TI  - LEARNING ATTRIBUTES OF DISEASE PROGRESSION FROM TRAJECTORIES OF SPARSE LAB
      VALUES.
AB  - There is heterogeneity in the manifestation of diseases, therefore it is
      essential to understand the patterns of progression of a disease in a given
      population for disease management as well as for clinical research. Disease
      status is often summarized by repeated recordings of one or more physiological
      measures. As a result, historical values of these physiological measures for a
      population sample can be used to characterize disease progression patterns. We
      use a method for clustering sparse functional data for identifying sub-groups
      within a cohort of patients with chronic kidney disease (CKD), based on the
      trajectories of their Creatinine measurements. We demonstrate through a proof-of
      principle study how the two sub-groups that display distinct patterns of disease
      progression may be compared on clinical attributes that correspond to the maximum
      difference in progression patterns. The key attributes that distinguish the two
      sub-groups appear to have support in published literature clinical practice
      related to CKD.

PMID- 27896975
TI  - COMPUTER AIDED IMAGE SEGMENTATION AND CLASSIFICATION FOR VIABLE AND NON-VIABLE
      TUMOR IDENTIFICATION IN OSTEOSARCOMA.
AB  - Osteosarcoma is one of the most common types of bone cancer in children. To gauge
      the extent of cancer treatment response in the patient after surgical resection,
      the H&E stained image slides are manually evaluated by pathologists to estimate
      the percentage of necrosis, a time consuming process prone to observer bias and
      inaccuracy. Digital image analysis is a potential method to automate this
      process, thus saving time and providing a more accurate evaluation. The slides
      are scanned in Aperio Scanscope, converted to digital Whole Slide Images (WSIs)
      and stored in SVS format. These are high resolution images, of the order of 109
      pixels, allowing up to 40X magnification factor. This paper proposes an image
      segmentation and analysis technique for segmenting tumor and non-tumor regions in
      histopathological WSIs of osteosarcoma datasets. Our approach is a combination of
      pixel-based and object-based methods which utilize tumor properties such as
      nuclei cluster, density, and circularity to classify tumor regions as viable and
      non-viable. A K-Means clustering technique is used for tumor isolation using
      color normalization, followed by multi-threshold Otsu segmentation technique to
      further classify tumor region as viable and non-viable. Then a Flood-fill
      algorithm is applied to cluster similar pixels into cellular objects and compute
      cluster data for further analysis of regions under study. To the best of our
      knowledge this is the first comprehensive solution that is able to produce such a
      classification for Osteosarcoma cancer. The results are very conclusive in
      identifying viable and non-viable tumor regions. In our experiments, the accuracy
      of the discussed approach is 100% in viable tumor and coagulative necrosis
      identification while it is around 90% for fibrosis and acellular/hypocellular
      tumor osteoid, for all the sampled datasets used. We expect the developed
      software to lead to a significant increase in accuracy and decrease in inter
      observer variability in assessment of necrosis by the pathologists and a
      reduction in the time spent by the pathologists in such assessments.

PMID- 27896977
TI  - A DEEP LEARNING APPROACH FOR CANCER DETECTION AND RELEVANT GENE IDENTIFICATION.
AB  - Cancer detection from gene expression data continues to pose a challenge due to
      the high dimensionality and complexity of these data. After decades of research
      there is still uncertainty in the clinical diagnosis of cancer and the
      identification of tumor-specific markers. Here we present a deep learning
      approach to cancer detection, and to the identification of genes critical for the
      diagnosis of breast cancer. First, we used Stacked Denoising Autoencoder (SDAE)
      to deeply extract functional features from high dimensional gene expression
      profiles. Next, we evaluated the performance of the extracted representation
      through supervised classification models to verify the usefulness of the new
      features in cancer detection. Lastly, we identified a set of highly interactive
      genes by analyzing the SDAE connectivity matrices. Our results and analysis
      illustrate that these highly interactive genes could be useful cancer biomarkers
      for the detection of breast cancer that deserve further studies.

PMID- 27896976
TI  - MISSING DATA IMPUTATION IN THE ELECTRONIC HEALTH RECORD USING DEEPLY LEARNED
      AUTOENCODERS.
AB  - Electronic health records (EHRs) have become a vital source of patient outcome
      data but the widespread prevalence of missing data presents a major challenge.
      Different causes of missing data in the EHR data may introduce unintentional
      bias. Here, we compare the effectiveness of popular multiple imputation
      strategies with a deeply learned autoencoder using the Pooled Resource Open
      Access ALS Clinical Trials Database (PRO-ACT). To evaluate performance, we
      examined imputation accuracy for known values simulated to be either missing
      completely at random or missing not at random. We also compared ALS disease
      progression prediction across different imputation models. Autoencoders showed
      strong performance for imputation accuracy and contributed to the strongest
      disease progression predictor. Finally, we show that despite clinical
      heterogeneity, ALS disease progression appears homogenous with time from onset
      being the most important predictor.

PMID- 27896978
TI  - DEVELOPMENT AND PERFORMANCE OF TEXT-MINING ALGORITHMS TO EXTRACT SOCIOECONOMIC
      STATUS FROM DE-IDENTIFIED ELECTRONIC HEALTH RECORDS.
AB  - Socioeconomic status (SES) is a fundamental contributor to health, and a key
      factor underlying racial disparities in disease. However, SES data are rarely
      included in genetic studies due in part to the difficultly of collecting these
      data when studies were not originally designed for that purpose. The emergence of
      large clinic-based biobanks linked to electronic health records (EHRs) provides
      research access to large patient populations with longitudinal phenotype data
      captured in structured fields as billing codes, procedure codes, and
      prescriptions. SES data however, are often not explicitly recorded in structured
      fields, but rather recorded in the free text of clinical notes and
      communications. The content and completeness of these data vary widely by
      practitioner. To enable gene-environment studies that consider SES as an
      exposure, we sought to extract SES variables from racial/ethnic minority adult
      patients (n=9,977) in BioVU, the Vanderbilt University Medical Center
      biorepository linked to de-identified EHRs. We developed several measures of SES
      using information available within the de-identified EHR, including broad
      categories of occupation, education, insurance status, and homelessness. Two
      hundred patients were randomly selected for manual review to develop a set of
      seven algorithms for extracting SES information from de-identified EHRs. The
      algorithms consist of 15 categories of information, with 830 unique search terms.
      SES data extracted from manual review of 50 randomly selected records were
      compared to data produced by the algorithm, resulting in positive predictive
      values of 80.0% (education), 85.4% (occupation), 87.5% (unemployment), 63.6%
      (retirement), 23.1% (uninsured), 81.8% (Medicaid), and 33.3% (homelessness),
      suggesting some categories of SES data are easier to extract in this EHR than
      others. The SES data extraction approach developed here will enable future EHR
      based genetic studies to integrate SES information into statistical analyses.
      Ultimately, incorporation of measures of SES into genetic studies will help
      elucidate the impact of the social environment on disease risk and outcomes.

PMID- 27896980
TI  - DEEP MOTIF DASHBOARD: VISUALIZING AND UNDERSTANDING GENOMIC SEQUENCES USING DEEP
      NEURAL NETWORKS.
AB  - Deep neural network (DNN) models have recently obtained state-of-the-art
      prediction accuracy for the transcription factor binding (TFBS) site
      classification task. However, it remains unclear how these approaches identify
      meaningful DNA sequence signals and give insights as to why TFs bind to certain
      locations. In this paper, we propose a toolkit called the Deep Motif Dashboard
      (DeMo Dashboard) which provides a suite of visualization strategies to extract
      motifs, or sequence patterns from deep neural network models for TFBS
      classification. We demonstrate how to visualize and understand three important
      DNN models: convolutional, recurrent, and convolutional-recurrent networks. Our
      first visualization method is finding a test sequence's saliency map which uses
      first-order derivatives to describe the importance of each nucleotide in making
      the final prediction. Second, considering recurrent models make predictions in a
      temporal manner (from one end of a TFBS sequence to the other), we introduce
      temporal output scores, indicating the prediction score of a model over time for
      a sequential input. Lastly, a class-specific visualization strategy finds the
      optimal input sequence for a given TFBS positive class via stochastic gradient
      optimization. Our experimental results indicate that a convolutional-recurrent
      architecture performs the best among the three architectures. The visualization
      techniques indicate that CNN-RNN makes predictions by modeling both motifs as
      well as dependencies among them.

PMID- 27896979
TI  - GENOME-WIDE INTERACTION WITH SELECTED TYPE 2 DIABETES LOCI REVEALS NOVEL LOCI FOR
      TYPE 2 DIABETES IN AFRICAN AMERICANS.
AB  - Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and
      insulin sensitivity, yet most T2D loci identified to date influence insulin
      secretion. We hypothesized that T2D loci, particularly those affecting insulin
      sensitivity, can be identified through interaction with known T2D loci implicated
      in insulin secretion. To test this hypothesis, single nucleotide polymorphisms
      (SNPs) nominally associated with acute insulin response to glucose (AIRg), a
      dynamic measure of first-phase insulin secretion, and previously associated with
      T2D in genome-wide association studies (GWAS) were identified in African
      Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n=492
      subjects). These SNPs were tested for interaction, individually and jointly as a
      genetic risk score (GRS), using GWAS data from five cohorts (ARIC, CARDIA, JHS,
      MESA, WFSM; n=2,725 cases, 4,167 controls) with T2D as the outcome. In single
      variant analyses, suggestively significant (Pinteraction < 5*10-6) interactions
      were observed at several loci including DGKB (rs978989), CDK18 (rs12126276),
      CXCL12 (rs7921850), HCN1 (rs6895191), FAM98A (rs1900780), and MGMT (rs568530).
      Notable beta-cell GRS interactions included two SNPs at the DGKB locus
      (rs6976381; rs6962498). These data support the hypothesis that additional genetic
      factors contributing to T2D risk can be identified by interactions with insulin
      secretion loci.

PMID- 27896981
TI  - META-ANALYSIS OF CONTINUOUS PHENOTYPES IDENTIFIES A GENE SIGNATURE THAT
      CORRELATES WITH COPD DISEASE STATUS.
AB  - The utility of multi-cohort two-class meta-analysis to identify robust
      differentially expressed gene signatures has been well established. However, many
      biomedical applications, such as gene signatures of disease progression, require
      one-class analysis. Here we describe an R package, MetaCorrelator, that can
      identify a reproducible transcriptional signature that is correlated with a
      continuous disease phenotype across multiple datasets. We successfully applied
      this framework to extract a pattern of gene expression that can predict lung
      function in patients with chronic obstructive pulmonary disease (COPD) in both
      peripheral blood mononuclear cells (PBMCs) and tissue. Our results point to a
      disregulation in the oxidation state of the lungs of patients with COPD, as well
      as underscore the classically recognized inammatory state that underlies this
      disease.

PMID- 27896982
TI  - PREDICTIVE MODELING OF HOSPITAL READMISSION RATES USING ELECTRONIC MEDICAL RECORD
      WIDE MACHINE LEARNING: A CASE-STUDY USING MOUNT SINAI HEART FAILURE COHORT.
AB  - Reduction of preventable hospital readmissions that result from chronic or acute
      conditions like stroke, heart failure, myocardial infarction and pneumonia
      remains a significant challenge for improving the outcomes and decreasing the
      cost of healthcare delivery in the United States. Patient readmission rates are
      relatively high for conditions like heart failure (HF) despite the implementation
      of high-quality healthcare delivery operation guidelines created by regulatory
      authorities. Multiple predictive models are currently available to evaluate
      potential 30-day readmission rates of patients. Most of these models are
      hypothesis driven and repetitively assess the predictive abilities of the same
      set of biomarkers as predictive features. In this manuscript, we discuss our
      attempt to develop a data-driven, electronic-medical record-wide (EMR-wide)
      feature selection approach and subsequent machine learning to predict readmission
      probabilities. We have assessed a large repertoire of variables from electronic
      medical records of heart failure patients in a single center. The cohort included
      1,068 patients with 178 patients were readmitted within a 30-day interval (16.66%
      readmission rate). A total of 4,205 variables were extracted from EMR including
      diagnosis codes (n=1,763), medications (n=1,028), laboratory measurements
      (n=846), surgical procedures (n=564) and vital signs (n=4). We designed a
      multistep modeling strategy using the Naive Bayes algorithm. In the first step,
      we created individual models to classify the cases (readmitted) and controls (non
      readmitted). In the second step, features contributing to predictive risk from
      independent models were combined into a composite model using a correlation-based
      feature selection (CFS) method. All models were trained and tested using a 5-fold
      cross-validation method, with 70% of the cohort used for training and the
      remaining 30% for testing. Compared to existing predictive models for HF
      readmission rates (AUCs in the range of 0.6-0.7), results from our EMR-wide
      predictive model (AUC=0.78; Accuracy=83.19%) and phenome-wide feature selection
      strategies are encouraging and reveal the utility of such datadriven machine
      learning. Fine tuning of the model, replication using multi-center cohorts and
      prospective clinical trial to evaluate the clinical utility would help the
      adoption of the model as a clinical decision system for evaluating readmission
      status.

PMID- 27896983
TI  - LEARNING PARSIMONIOUS ENSEMBLES FOR UNBALANCED COMPUTATIONAL GENOMICS PROBLEMS.
AB  - Prediction problems in biomedical sciences are generally quite difficult,
      partially due to incomplete knowledge of how the phenomenon of interest is
      influenced by the variables and measurements used for prediction, as well as a
      lack of consensus regarding the ideal predictor(s) for specific problems. In
      these situations, a powerful approach to improving prediction performance is to
      construct ensembles that combine the outputs of many individual base predictors,
      which have been successful for many biomedical prediction tasks. Moreover,
      selecting a parsimonious ensemble can be of even greater value for biomedical
      sciences, where it is not only important to learn an accurate predictor, but also
      to interpret what novel knowledge it can provide about the target problem.
      Ensemble selection is a promising approach for this task because of its ability
      to select a collectively predictive subset, often a relatively small one, of all
      input base predictors. One of the most well-known algorithms for ensemble
      selection, CES (Caruana et al.'s Ensemble Selection), generally performs well in
      practice, but faces several challenges due to the difficulty of choosing the
      right values of its various parameters. Since the choices made for these
      parameters are usually ad-hoc, good performance of CES is difficult to guarantee
      for a variety of problems or datasets. To address these challenges with CES and
      other such algorithms, we propose a novel heterogeneous ensemble selection
      approach based on the paradigm of reinforcement learning (RL), which offers a
      more systematic and mathematically sound methodology for exploring the many
      possible combinations of base predictors that can be selected into an ensemble.
      We develop three RL-based strategies for constructing ensembles and analyze their
      results on two unbalanced computational genomics problems, namely the prediction
      of protein function and splice sites in eukaryotic genomes. We show that the
      resultant ensembles are indeed substantially more parsimonious as compared to the
      full set of base predictors, yet still offer almost the same classification
      power, especially for larger datasets. The RL ensembles also yield a better
      combination of parsimony and predictive performance as compared to CES.

PMID- 27896984
TI  - METHODS FOR CLUSTERING TIME SERIES DATA ACQUIRED FROM MOBILE HEALTH APPS.
AB  - In our recent Asthma Mobile Health Study (AMHS), thousands of asthma patients
      across the country contributed medical data through the iPhone Asthma Health App
      on a daily basis for an extended period of time. The collected data included
      daily self-reported asthma symptoms, symptom triggers, and real time geographic
      location information. The AMHS is just one of many studies occurring in the
      context of now many thousands of mobile health apps aimed at improving wellness
      and better managing chronic disease conditions, leveraging the passive and active
      collection of data from mobile, handheld smart devices. The ability to identify
      patient groups or patterns of symptoms that might predict adverse outcomes such
      as asthma exacerbations or hospitalizations from these types of large,
      prospectively collected data sets, would be of significant general interest.
      However, conventional clustering methods cannot be applied to these types of
      longitudinally collected data, especially survey data actively collected from app
      users, given heterogeneous patterns of missing values due to: 1) varying survey
      response rates among different users, 2) varying survey response rates over time
      of each user, and 3) non-overlapping periods of enrollment among different users.
      To handle such complicated missing data structure, we proposed a probability
      imputation model to infer missing data. We also employed a consensus clustering
      strategy in tandem with the multiple imputation procedure. Through simulation
      studies under a range of scenarios reflecting real data conditions, we identified
      favorable performance of the proposed method over other strategies that impute
      the missing value through low-rank matrix completion. When applying the proposed
      new method to study asthma triggers and symptoms collected as part of the AMHS,
      we identified several patient groups with distinct phenotype patterns. Further
      validation of the methods described in this paper might be used to identify
      clinically important patterns in large data sets with complicated missing data
      structure, improving the ability to use such data sets to identify at-risk
      populations for potential intervention.

PMID- 27896985
TI  - A NEW RELEVANCE ESTIMATOR FOR THE COMPILATION AND VISUALIZATION OF DISEASE
      PATTERNS AND POTENTIAL DRUG TARGETS.
AB  - A new computational method is presented to extract disease patterns from
      heterogeneous and text-based data. For this study, 22 million PubMed records were
      mined for co-occurrences of gene name synonyms and disease MeSH terms. The
      resulting publication counts were transferred into a matrix Mdata. In this
      matrix, a disease was represented by a row and a gene by a column. Each field in
      the matrix represented the publication count for a co-occurring disease-gene
      pair. A second matrix with identical dimensions Mrelevance was derived from
      Mdata. To create Mrelevance the values from Mdata were normalized. The normalized
      values were multiplied by the column-wise calculated Gini coefficient. This
      multiplication resulted in a relevance estimator for every gene in relation to a
      disease. From Mrelevance the similarities between all row vectors were
      calculated. The resulting similarity matrix Srelevance related 5,000 diseases by
      the relevance estimators calculated for 15,000 genes. Three diseases were
      analyzed in detail for the validation of the disease patterns and the relevant
      genes. Cytoscape was used to visualize and to analyze Mrelevance and Srelevance
      together with the genes and diseases. Summarizing the results, it can be stated
      that the relevance estimator introduced here was able to detect valid disease
      patterns and to identify genes that encoded key proteins and potential targets
      for drug discovery projects.

PMID- 27896986
TI  - NETWORK MAP OF ADVERSE HEALTH EFFECTS AMONG VICTIMS OF INTIMATE PARTNER VIOLENCE.
AB  - Intimate partner violence (IPV) is a serious problem with devastating health
      consequences. Screening procedures may overlook relationships between IPV and
      negative health effects. To identify IPV-associated women's health issues, we
      mined national, aggregated de-identified electronic health record data and
      compared female health issues of domestic abuse (DA) versus non-DA records,
      identifying terms significantly more frequent for the DA group. After coding
      these terms into 28 broad categories, we developed a network map to determine
      strength of relationships between categories in the context of DA, finding that
      acute conditions are strongly connected to cardiovascular, gastrointestinal,
      gynecological, and neurological conditions among victims.

PMID- 27896987
TI  - DISCOVERY OF FUNCTIONAL AND DISEASE PATHWAYS BY COMMUNITY DETECTION IN PROTEIN
      PROTEIN INTERACTION NETWORKS.
AB  - Advances in cellular, molecular, and disease biology depend on the comprehensive
      characterization of gene interactions and pathways. Traditionally, these pathways
      are curated manually, limiting their efficient annotation and, potentially,
      reinforcing field-specific bias. Here, in order to test objective and automated
      identification of functionally cooperative genes, we compared a novel algorithm
      with three established methods to search for communities within gene interaction
      networks. Communities identified by the novel approach and by one of the
      established method overlapped significantly (q < 0.1) with control pathways. With
      respect to disease, these communities were biased to genes with pathogenic
      variants in ClinVar (p ? 0.01), and often genes from the same community were co
      expressed, including in breast cancers. The interesting subset of novel
      communities, defined by poor overlap to control pathways also contained co
      expressed genes, consistent with a possible functional role. This work shows that
      community detection based on topological features of networks suggests new,
      biologically meaningful groupings of genes that, in turn, point to health and
      disease relevant hypotheses.

PMID- 27896988
TI  - PRECISION MEDICINE: DATA AND DISCOVERY FOR IMPROVED HEALTH AND THERAPY.
AB  - The major goal of precision medicine is to improve human health. A feature that
      unites much research in the field is the use of large datasets such as genomic
      data and electronic health records. Research in this field includes examination
      of variation in the core bases of DNA and their methylation status, through
      variations in metabolic and signaling molecules, all the way up to broader
      systems level changes in physiology and disease presentation. Intermediate goals
      include understanding the individual drivers of disease that differentiate the
      cause of disease in each individual. To match this development of approaches to
      physical and activitybased measurements, computational approaches to using these
      new streams of data to better understand improve human health are being rapidly
      developed by the thriving biomedical informatics research community. This session
      of the 2017 Pacific Symposium of Biocomputing presents some of the latest
      advances in the capture, analysis and use of diverse biomedical data in precision
      medicine.

PMID- 27896989
TI  - OPENING THE DOOR TO THE LARGE SCALE USE OF CLINICAL LAB MEASURES FOR ASSOCIATION
      TESTING: EXPLORING DIFFERENT METHODS FOR DEFINING PHENOTYPES.
AB  - The past decade has seen exponential growth in the numbers of sequenced and
      genotyped individuals and a corresponding increase in our ability of collect and
      catalogue phenotypic data for use in the clinic. We now face the challenge of
      integrating these diverse data in new ways new that can provide useful
      diagnostics and precise medical interventions for individual patients. One of the
      first steps in this process is to accurately map the phenotypic consequences of
      the genetic variation in human populations. The most common approach for this is
      the genome wide association study (GWAS). While this technique is relatively
      simple to implement for a given phenotype, the choice of how to define a
      phenotype is critical. It is becoming increasingly common for each individual in
      a GWAS cohort to have a large profile of quantitative measures. The standard
      approach is to test for associations with one measure at a time; however, there
      are many justifiable ways to define a set of phenotypes, and the genetic
      associations that are revealed will vary based on these definitions. Some
      phenotypes may only show a significant genetic association signal when considered
      together, such as through principle components analysis (PCA). Combining
      correlated measures may increase the power to detect association by reducing the
      noise present in individual variables and reduce the multiple hypothesis testing
      burden. Here we show that PCA and k-means clustering are two complimentary
      methods for identifying novel genotype-phenotype relationships within a set of
      quantitative human traits derived from the Geisinger Health System electronic
      health record (EHR). Using a diverse set of approaches for defining phenotype may
      yield more insights into the genetic architecture of complex traits and the
      findings presented here highlight a clear need for further investigation into
      other methods for defining the most relevant phenotypes in a set of variables. As
      the data of EHR continue to grow, addressing these issues will become
      increasingly important in our efforts to use genomic data effectively in
      medicine.

PMID- 27896991
TI  - TEMPORAL ORDER OF DISEASE PAIRS AFFECTS SUBSEQUENT DISEASE TRAJECTORIES: THE CASE
      OF DIABETES AND SLEEP APNEA.
AB  - Most studies of disease etiologies focus on one disease only and not the full
      spectrum of multimorbidities that many patients have. Some disease pairs have
      shared causal origins, others represent common follow-on diseases, while yet
      other co-occurring diseases may manifest themselves in random order of
      appearance. We discuss these different types of disease co-occurrences, and use
      the two diseases "sleep apnea" and "diabetes" to showcase the approach which
      otherwise can be applied to any disease pair. We benefit from seven million
      electronic medical records covering the entire population of Denmark for more
      than 20 years. Sleep apnea is the most common sleep-related breathing disorder
      and it has previously been shown to be bidirectionally linked to diabetes,
      meaning that each disease increases the risk of acquiring the other. We confirm
      that there is no significant temporal relationship, as approximately half of
      patients with both diseases are diagnosed with diabetes first. However, we also
      show that patients diagnosed with diabetes before sleep apnea have a higher
      disease burden compared to patients diagnosed with sleep apnea before diabetes.
      The study clearly demonstrates that it is not only the diagnoses in the patient's
      disease history that are important, but also the specific order in which these
      diagnosis are given that matters in terms of outcome. We suggest that this should
      be considered for patient stratification.

PMID- 27896990
TI  - A POWERFUL METHOD FOR INCLUDING GENOTYPE UNCERTAINTY IN TESTS OF HARDY-WEINBERG
      EQUILIBRIUM.
AB  - The use of posterior probabilities to summarize genotype uncertainty is pervasive
      across genotype, sequencing and imputation platforms. Prior work in many contexts
      has shown the utility of incorporating genotype uncertainty (posterior
      probabilities) in downstream statistical tests. Typical approaches to
      incorporating genotype uncertainty when testing Hardy-Weinberg equilibrium tend
      to lack calibration in the type I error rate, especially as genotype uncertainty
      increases. We propose a new approach in the spirit of genomic control that
      properly calibrates the type I error rate, while yielding improved power to
      detect deviations from Hardy-Weinberg Equilibrium. We demonstrate the improved
      performance of our method on both simulated and real genotypes.

PMID- 27896992
TI  - MICRORNA-AUGMENTED PATHWAYS (mirAP) AND THEIR APPLICATIONS TO PATHWAY ANALYSIS
      AND DISEASE SUBTYPING.
AB  - MicroRNAs play important roles in the development of many complex diseases.
      Because of their importance, the analysis of signaling pathways including miRNA
      interactions holds the potential for unveiling the mechanisms underlying such
      diseases. However, current signaling pathway databases are limited to
      interactions between genes and ignore miRNAs. Here, we use the information on
      miRNA targets to build a database of miRNA-augmented pathways (mirAP), and we
      show its application in the contexts of integrative pathway analysis and disease
      subtyping. Our miRNA-mRNA integrative pathway analysis pipeline incorporates a
      topology-aware approach that we previously implemented. Our integrative disease
      subtyping pipeline takes into account survival data, gene and miRNA expression,
      and knowledge of the interactions among genes. We demonstrate the advantages of
      our approach by analyzing nine sample-matched datasets that provide both miRNA
      and mRNA expression. We show that integrating miRNAs into pathway analysis
      results in greater statistical power, and provides a more comprehensive view of
      the underlying phenomena. We also compare our disease subtyping method with the
      state-of-the-art integrative analysis by analyzing a colorectal cancer database
      from TCGA. The colorectal cancer subtypes identified by our approach are
      significantly different in terms of their survival expectation. These miRNA
      augmented pathways offer a more comprehensive view and a deeper understanding of
      biological pathways. A better understanding of the molecular processes associated
      with patients' survival can help to a better prognosis and an appropriate
      treatment for each subtype.

PMID- 27896994
TI  - HUMAN KINASES DISPLAY MUTATIONAL HOTSPOTS AT COGNATE POSITIONS WITHIN CANCER.
AB  - The discovery of driver genes is a major pursuit of cancer genomics, usually
      based on observing the same mutation in different patients. But the heterogeneity
      of cancer pathways plus the high background mutational frequency of tumor cells
      often cloud the distinction between less frequent drivers and innocent passenger
      mutations. Here, to overcome these disadvantages, we grouped together mutations
      from close kinase paralogs under the hypothesis that cognate mutations may
      functionally favor cancer cells in similar ways. Indeed, we find that kinase
      paralogs often bear mutations to the same substituted amino acid at the same
      aligned positions and with a large predicted Evolutionary Action. Functionally,
      these high Evolutionary Action, non-random mutations affect known kinase motifs,
      but strikingly, they do so differently among different kinase types and cancers,
      consistent with differences in selective pressures. Taken together, these results
      suggest that cancer pathways may flexibly distribute a dependence on a given
      functional mutation among multiple close kinase paralogs. The recognition of this
      "mutational delocalization" of cancer drivers among groups of paralogs is a new
      phenomena that may help better identify relevant mechanisms and therefore
      eventually guide personalized therapy.

PMID- 27896995
TI  - MUSE: A MULTI-LOCUS SAMPLING-BASED EPISTASIS ALGORITHM FOR QUANTITATIVE GENETIC
      TRAIT PREDICTION.
AB  - Quantitative genetic trait prediction based on high-density genotyping arrays
      plays an important role for plant and animal breeding, as well as genetic
      epidemiology such as complex diseases. The prediction can be very helpful to
      develop breeding strategies and is crucial to translate the findings in genetics
      to precision medicine. Epistasis, the phenomena where the SNPs interact with each
      other, has been studied extensively in Genome Wide Association Studies (GWAS) but
      received relatively less attention for quantitative genetic trait prediction. As
      the number of possible interactions is generally extremely large, even pairwise
      interactions is very challenging. To our knowledge, there is no solid solution
      yet to utilize epistasis to improve genetic trait prediction. In this work, we
      studied the multi-locus epistasis problem where the interactions with more than
      two SNPs are considered. We developed an effcient algorithm MUSE to improve the
      genetic trait prediction with the help of multi-locus epistasis. MUSE is sampling
      based and we proposed a few different sampling strategies. Our experiments on
      real data showed that MUSE is not only effcient but also effective to improve the
      genetic trait prediction. MUSE also achieved very significant improvements on a
      real plant data set as well as a real human data set.

PMID- 27896993
TI  - FREQUENT SUBGRAPH MINING OF PERSONALIZED SIGNALING PATHWAY NETWORKS GROUPS
      PATIENTS WITH FREQUENTLY DYSREGULATED DISEASE PATHWAYS AND PREDICTS PROGNOSIS.
AB  - MOTIVATION: Large scale genomics studies have generated comprehensive molecular
      characterization of numerous cancer types. Subtypes for many tumor types have
      been established; however, these classifications are based on molecular
      characteristics of a small gene sets with limited power to detect dysregulation
      at the patient level. We hypothesize that frequent graph mining of pathways to
      gather pathways functionally relevant to tumors can characterize tumor types and
      provide opportunities for personalized therapies. RESULTS: In this study we
      present an integrative omics approach to group patients based on their altered
      pathway characteristics and show prognostic differences within breast cancer (p <
      9:57E - 10) and glioblastoma multiforme (p < 0:05) patients. We were able
      validate this approach in secondary RNA-Seq datasets with p < 0:05 and p < 0:01
      respectively. We also performed pathway enrichment analysis to further
      investigate the biological relevance of dysregulated pathways. We compared our
      approach with network-based classifier algorithms and showed that our
      unsupervised approach generates more robust and biologically relevant clustering
      whereas previous approaches failed to report specific functions for similar
      patient groups or classify patients into prognostic groups. CONCLUSIONS: These
      results could serve as a means to improve prognosis for future cancer patients,
      and to provide opportunities for improved treatment options and personalized
      interventions. The proposed novel graph mining approach is able to integrate PPI
      networks with gene expression in a biologically sound approach and cluster
      patients in to clinically distinct groups. We have utilized breast cancer and
      glioblastoma multiforme datasets from microarray and RNA-Seq platforms and
      identified disease mechanisms differentiating samples. SUPPLEMENTARY INFORMATION:
      Supplementary methods, figures, tables and code are available at
      https://github.com/bebeklab/dysprog.

PMID- 27896996
TI  - CERNA SEARCH METHOD IDENTIFIED A MET-ACTIVATED SUBGROUP AMONG EGFR DNA AMPLIFIED
      LUNG ADENOCARCINOMA PATIENTS.
AB  - Given the diverse molecular pathways involved in tumorigenesis, identifying
      subgroups among cancer patients is crucial in precision medicine. While most
      targeted therapies rely on DNA mutation status in tumors, responses to such
      therapies vary due to the many molecular processes involved in propagating DNA
      changes to proteins (which constitute the usual drug targets). Though RNA
      expressions have been extensively used to categorize tumors, identifying
      clinically important subgroups remains challenging given the difficulty of
      discerning subgroups within all possible RNA-RNA networks. It is thus essential
      to incorporate multiple types of data. Recently, RNA was found to regulate other
      RNA through a common microRNA (miR). These regulating and regulated RNAs are
      referred to as competing endogenous RNAs (ceRNAs). However, global correlations
      between mRNA and miR expressions across all samples have not reliably yielded
      ceRNAs. In this study, we developed a ceRNA-based method to identify subgroups of
      cancer patients combining DNA copy number variation, mRNA expression, and
      microRNA (miR) expression data with biological knowledge. Clinical data is used
      to validate identified subgroups and ceRNAs. Since ceRNAs are causal, ceRNA-based
      subgroups may present clinical relevance. Using lung adenocarcinoma data from The
      Cancer Genome Atlas (TCGA) as an example, we focused on EGFR amplification
      status, since a targeted therapy for EGFR exists. We hypothesized that global
      correlations between mRNA and miR expressions across all patients would not
      reveal important subgroups and that clustering of potential ceRNAs might define
      molecular pathway-relevant subgroups. Using experimentally validated miR-target
      pairs, we identified EGFR and MET as potential ceRNAs for miR-133b in lung
      adenocarcinoma. The EGFR-MET up and miR-133b down subgroup showed a higher death
      rate than the EGFR-MET down and miR-133b up subgroup. Although transactivation
      between MET and EGFR has been identified previously, our result is the first to
      propose ceRNA as one of its underlying mechanisms. Furthermore, since MET
      amplification was seen in the case of resistance to EGFR-targeted therapy, the
      EGFR-MET up and miR-133b down subgroup may fall into the drug non-response group
      and thus preclude EGFR target therapy.

PMID- 27896997
TI  - IMPROVED PERFORMANCE OF GENE SET ANALYSIS ON GENOME-WIDE TRANSCRIPTOMICS DATA
      WHEN USING GENE ACTIVITY STATE ESTIMATES.
AB  - Gene set analysis methods continue to be a popular and powerful method of
      evaluating genome-wide transcriptomics data. These approach require a priori
      grouping of genes into biologically meaningful sets, and then conducting
      downstream analyses at the set (instead of gene) level of analysis. Gene set
      analysis methods have been shown to yield more powerful statistical conclusions
      than single-gene analyses due to both reduced multiple testing penalties and
      potentially larger observed effects due to the aggregation of effects across
      multiple genes in the set. Traditionally, gene set analysis methods have been
      applied directly to normalized, log-transformed, transcriptomics data. Recently,
      efforts have been made to transform transcriptomics data to scales yielding more
      biologically interpretable results. For example, recently proposed models
      transform log-transformed transcriptomics data to a confidence metric (ranging
      between 0 and 100%) that a gene is active (roughly speaking, that the gene
      product is part of an active cellular mechanism). In this manuscript, we
      demonstrate, on both real and simulated transcriptomics data, that tests for
      differential expression between sets of genes using are typically more powerful
      when using gene activity state estimates as opposed to log-transformed gene
      expression data. Our analysis suggests further exploration of techniques to
      transform transcriptomics data to meaningful quantities for improved downstream
      inference.

PMID- 27896998
TI  - methylDMV: SIMULTANEOUS DETECTION OF DIFFERENTIAL DNA METHYLATION AND VARIABILITY
      WITH CONFOUNDER ADJUSTMENT.
AB  - DNA methylation has emerged as promising epigenetic markers for disease
      diagnosis. Both the differential mean (DM) and differential variability (DV) in
      methylation have been shown to contribute to transcriptional aberration and
      disease pathogenesis. The presence of confounding factors in large scale EWAS may
      affect the methylation values and hamper accurate marker discovery. In this
      paper, we propose a exible framework called methylDMV which allows for
      confounding factors adjustment and enables simultaneous characterization and
      identification of CpGs exhibiting DM only, DV only and both DM and DV. The
      proposed framework also allows for prioritization and selection of candidate
      features to be included in the prediction algorithm. We illustrate the utility of
      methylDMV in several TCGA datasets. An R package methylDMV implementing our
      proposed method is available at
      http://www.ams.sunysb.edu/~pfkuan/softwares.html#methylDMV.

PMID- 27896999
TI  - IDENTIFY CANCER DRIVER GENES THROUGH SHARED MENDELIAN DISEASE PATHOGENIC VARIANTS
      AND CANCER SOMATIC MUTATIONS.
AB  - Genomic sequencing studies in the past several years have yielded a large number
      of cancer somatic mutations. There remains a major challenge in delineating a
      small fraction of somatic mutations that are oncogenic drivers from a background
      of predominantly passenger mutations. Although computational tools have been
      developed to predict the functional impact of mutations, their utility is
      limited. In this study, we applied an alternative approach to identify
      potentially novel cancer drivers as those somatic mutations that overlap with
      known pathogenic mutations in Mendelian diseases. We hypothesize that those
      shared mutations are more likely to be cancer drivers because they have the
      established molecular mechanisms to impact protein functions. We first show that
      the overlap between somatic mutations in COSMIC and pathogenic genetic variants
      in HGMD is associated with high mutation frequency in cancers and is enriched for
      known cancer genes. We then attempted to identify putative tumor suppressors
      based on the number of distinct HGMD/COSMIC overlapping mutations in a given
      gene, and our results suggest that ion channels, collagens and Marfan syndrome
      associated genes may represent new classes of tumor suppressors. To elucidate
      potentially novel oncogenes, we identified those HGMD/COSMIC overlapping
      mutations that are not only highly recurrent but also mutually exclusive from
      previously characterized oncogenic mutations in each specific cancer type. Taken
      together, our study represents a novel approach to discover new cancer genes from
      the vast amount of cancer genome sequencing data.

PMID- 27897000
TI  - IDENTIFYING CANCER SPECIFIC METABOLIC SIGNATURES USING CONSTRAINT-BASED MODELS.
AB  - Cancer metabolism differs remarkably from the metabolism of healthy surrounding
      tissues, and it is extremely heterogeneous across cancer types. While these
      metabolic differences provide promising avenues for cancer treatments, much work
      remains to be done in understanding how metabolism is rewired in malignant
      tissues. To that end, constraint-based models provide a powerful computational
      tool for the study of metabolism at the genome scale. To generate meaningful
      predictions, however, these generalized human models must first be tailored for
      specific cell or tissue sub-types. Here we first present two improved algorithms
      for (1) the generation of these context-specific metabolic models based on omics
      data, and (2) Monte-Carlo sampling of the metabolic model ux space. By applying
      these methods to generate and analyze context-specific metabolic models of
      diverse solid cancer cell line data, and primary leukemia pediatric patient
      biopsies, we demonstrate how the methodology presented in this study can generate
      insights into the rewiring differences across solid tumors and blood cancers.

PMID- 27897001
TI  - DIFFERENTIAL PATHWAY DEPENDENCY DISCOVERY ASSOCIATED WITH DRUG RESPONSE ACROSS
      CANCER CELL LINES.
AB  - The effort to personalize treatment plans for cancer patients involves the
      identification of drug treatments that can effectively target the disease while
      minimizing the likelihood of adverse reactions. In this study, the gene
      expression profile of 810 cancer cell lines and their response data to 368 small
      molecules from the Cancer Therapeutics Research Portal (CTRP) are analyzed to
      identify pathways with significant rewiring between genes, or differential gene
      dependency, between sensitive and non-sensitive cell lines. Identified pathways
      and their corresponding differential dependency networks are further analyzed to
      discover essentiality and specificity mediators of cell line response to
      drugs/compounds. For analysis we use the previously published method EDDY
      (Evaluation of Differential DependencY). EDDY first constructs likelihood
      distributions of gene-dependency networks, aided by known genegene interaction,
      for two given conditions, for example, sensitive cell lines vs. non-sensitive
      cell lines. These sets of networks yield a divergence value between two
      distributions of network likelihoods that can be assessed for significance using
      permutation tests. Resulting differential dependency networks are then further
      analyzed to identify genes, termed mediators, which may play important roles in
      biological signaling in certain cell lines that are sensitive or non-sensitive to
      the drugs. Establishing statistical correspondence between compounds and
      mediators can improve understanding of known gene dependencies associated with
      drug response while also discovering new dependencies. Millions of compute hours
      resulted in thousands of these statistical discoveries. EDDY identified 8,811
      statistically significant pathways leading to 26,822 compound-pathway-mediator
      triplets. By incorporating STITCH and STRING databases, we could construct
      evidence networks for 14,415 compound-pathway-mediator triplets for support. The
      results of this analysis are presented in a searchable website to aid researchers
      in studying potential molecular mechanisms underlying cells' drug response as
      well as in designing experiments for the purpose of personalized treatment
      regimens.

PMID- 27897002
TI  - A METHYLATION-TO-EXPRESSION FEATURE MODEL FOR GENERATING ACCURATE PROGNOSTIC RISK
      SCORES AND IDENTIFYING DISEASE TARGETS IN CLEAR CELL KIDNEY CANCER.
AB  - Many researchers now have available multiple high-dimensional molecular and
      clinical datasets when studying a disease. As we enter this multi-omic era of
      data analysis, new approaches that combine different levels of data (e.g. at the
      genomic and epigenomic levels) are required to fully capitalize on this
      opportunity. In this work, we outline a new approach to multi-omic data
      integration, which combines molecular and clinical predictors as part of a single
      analysis to create a prognostic risk score for clear cell renal cell carcinoma.
      The approach integrates data in multiple ways and yet creates models that are
      relatively straightforward to interpret and with a high level of performance.
      Furthermore, the proposed process of data integration captures relationships in
      the data that represent highly disease-relevant functions.